sha,source_x,title,doi,pmcid,pubmed_id,license,abstract,publish_time,authors,journal,Microsoft Academic Paper ID,WHO #Covidence,has_full_text
c630ebcdf30652f0422c3ec12a00b50241dc9bd9,CZI,Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target,10.1007/s00134-020-05985-9,,32125455,cc-by-nc,,2020,"Zhang, Haibo; Penninger, Josef M.; Li, Yimin; Zhong, Nanshan; Slutsky, Arthur S.",Intensive Care Med,2002765492,#3252,True
53eccda7977a31e3d0f565c884da036b1e85438e,CZI,Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations,10.1038/s41421-020-0147-1,,,cc-by,,2020,"Cao, Yanan; Li, Lin; Feng, Zhimin; Wan, Shengqing; Huang, Peide; Sun, Xiaohui; Wen, Fang; Huang, Xuanlin; Ning, Guang; Wang, Weiqing",Cell Discovery,3003430844,#1861,True
210a892deb1c61577f6fba58505fd65356ce6636,CZI,Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data,10.3390/jcm9020538,,,cc-by,"The geographic spread of 2019 novel coronavirus (COVID-19) infections from the epicenter of Wuhan, China, has provided an opportunity to study the natural history of the recently emerged virus. Using publicly available event-date data from the ongoing epidemic, the present study investigated the incubation period and other time intervals that govern the epidemiological dynamics of COVID-19 infections. Our results show that the incubation period falls within the range of 2–14 days with 95% confidence and has a mean of around 5 days when approximated using the best-fit lognormal distribution. The mean time from illness onset to hospital admission (for treatment and/or isolation) was estimated at 3–4 days without truncation and at 5–9 days when right truncated. Based on the 95th percentile estimate of the incubation period, we recommend that the length of quarantine should be at least 14 days. The median time delay of 13 days from illness onset to death (17 days with right truncation) should be considered when estimating the COVID-19 case fatality risk.",2020,"Linton, M. Natalie; Kobayashi, Tetsuro; Yang, Yichi; Hayashi, Katsuma; Akhmetzhanov, R. Andrei; Jung, Sung-mok; Yuan, Baoyin; Kinoshita, Ryo; Nishiura, Hiroshi",Journal of Clinical Medicine,3006065484,#1043,True
e3b40cc8e0e137c416b4a2273a4dca94ae8178cc,CZI,Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China,10.3390/jcm9020575,,32093211,cc-by,"In December 2019, cases of unidentified pneumonia with a history of exposure in the Huanan Seafood Market were reported in Wuhan, Hubei Province. A novel coronavirus, SARS-CoV-2, was identified to be accountable for this disease. Human-to-human transmission is confirmed, and this disease (named COVID-19 by World Health Organization (WHO)) spread rapidly around the country and the world. As of 18 February 2020, the number of confirmed cases had reached 75,199 with 2009 fatalities. The COVID-19 resulted in a much lower case-fatality rate (about 2.67%) among the confirmed cases, compared with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Among the symptom composition of the 45 fatality cases collected from the released official reports, the top four are fever, cough, short of breath, and chest tightness/pain. The major comorbidities of the fatality cases include hypertension, diabetes, coronary heart disease, cerebral infarction, and chronic bronchitis. The source of the virus and the pathogenesis of this disease are still unconfirmed. No specific therapeutic drug has been found. The Chinese Government has initiated a level-1 public health response to prevent the spread of the disease. Meanwhile, it is also crucial to speed up the development of vaccines and drugs for treatment, which will enable us to defeat COVID-19 as soon as possible.",2020,"Deng, Sheng-Qun; Peng, Hong-Juan",J Clin Med,177663115,#1999,True
92c2c9839304b4f2bc1276d41b1aa885d8b364fd,CZI,Imaging changes in severe COVID-19 pneumonia,10.1007/s00134-020-05976-w,,32125453,cc-by-nc,,2020,"Zhang, Wei",Intensive Care Med,3006643024,#3242,False
0df0d5270a9399cf4e23c0cdd877a80616a9725e,CZI,An updated estimation of the risk of transmission of the novel coronavirus (2019-nCov),10.1016/j.idm.2020.02.001,,,cc-by-nc-nd,"The basic reproduction number of an infectious agent is the average number of infections one case can generate over the course of the infectious period, in a naïve, uninfected population. It is well-known that the estimation of this number may vary due to several methodological issues, including different assumptions and choice of parameters, utilized models, used datasets and estimation period. With the spreading of the novel coronavirus (2019-nCoV) infection, the reproduction number has been found to vary, reflecting the dynamics of transmission of the coronavirus outbreak as well as the case reporting rate. Due to significant variations in the control strategies, which have been changing over time, and thanks to the introduction of detection technologies that have been rapidly improved, enabling to shorten the time from infection/symptoms onset to diagnosis, leading to faster confirmation of the new coronavirus cases, our previous estimations on the transmission risk of the 2019-nCoV need to be revised. By using time-dependent contact and diagnose rates, we refit our previously proposed dynamics transmission model to the data available until January 29th 2020 and re-estimated the effective daily reproduction ratio that better quantifies the evolution of the interventions. We estimated when the effective daily reproduction ratio has fallen below 1 and when the epidemics will peak. Our updated findings suggest that the best measure is persistent and strict self-isolation. The epidemics will continue to grow, and can peak soon with the peak time depending highly on the public health interventions practically implemented.",2020,"Tang, Biao; Bragazzi, Nicola Luigi; Li, Qian; Tang, Sanyi; Xiao, Yanni; Wu, Jianhong",Infectious Disease Modelling,3006028839,#729,True
f24242580be243d5fc3f432915d86af6854bb8b7,CZI,"Real-time forecasts of the 2019-nCoV epidemic in China from February 5th to February 24th, 2020",10.1016/j.idm.2020.02.002,,,cc-by-nc-nd,"The initial cluster of severe pneumonia cases that triggered the 2019-nCoV epidemic was identified in Wuhan, China in December 2019. While early cases of the disease were linked to a wet market, human-to-human transmission has driven the rapid spread of the virus throughout China. The Chinese government has implemented containment strategies of city-wide lockdowns, screening at airports and train stations, and isolation of suspected patients; however, the cumulative case count keeps growing every day. The ongoing outbreak presents a challenge for modelers, as limited data are available on the early growth trajectory, and the epidemiological characteristics of the novel coronavirus are yet to be fully elucidated. We use phenomenological models that have been validated during previous outbreaks to generate and assess short-term forecasts of the cumulative number of confirmed reported cases in Hubei province, the epicenter of the epidemic, and for the overall trajectory in China, excluding the province of Hubei. We collect daily reported cumulative case data for the 2019-nCoV outbreak for each Chinese province from the National Health Commission of China. Here, we provide 5, 10, and 15 day forecasts for five consecutive days, February 5th through February 9th, with quantified uncertainty based on a generalized logistic growth model, the Richards growth model, and a sub-epidemic wave model. Our most recent forecasts reported here based on data up until February 9, 2020, largely agree across the three models presented and suggest an average range of 7,409 – 7,496 additional cases in Hubei and 1,128 – 1,929 additional cases in other provinces within the next five days. Models also predict an average total cumulative case count between 37,415 – 38,028 in Hubei and 11,588 – 13,499 in other provinces by February 24, 2020. Mean estimates and uncertainty bounds for both Hubei and other provinces have remained relatively stable in the last three reporting dates (February 7th – 9th). We also observe that each of the models predicts that the epidemic has reached saturation in both Hubei and other provinces. Our findings suggest that the containment strategies implemented in China are successfully reducing transmission and that the epidemic growth has slowed in recent days.",2020,"Roosa, K.; Lee, Y.; Luo, R.; Kirpich, A.; Rothenberg, R.; Hyman, J. M.; Yan, P.; Chowell, G.",Infectious Disease Modelling,3006028741,#865,True
d13a685f861b0f1ba05afa6e005311ad1820fd3a,CZI,RETRACTED: Chinese medical staff request international medical assistance in fighting against COVID-19,10.1016/s2214-109x(20)30065-6,,32105614,cc-by,,2020,"Zeng, Yingchun; Zhen, Yan",The Lancet. Global health,2627046314,#5386,False
e1b336d8be1a4c0ccc5a1bf41e48b3b004d3ece1,CZI,COVID-19 outbreak on the Diamond Princess cruise ship: estimating the epidemic potential and effectiveness of public health countermeasures,10.1093/jtm/taaa030,,,cc-by-nc,"Cruise ships carry a large number of people in confined spaces with relative homogeneous mixing. On 3 February, 2020, an outbreak of COVID-19 on cruise ship Diamond Princess was reported with 10 initial cases, following an index case on board around 21-25 January. By 4 February, public health measures such as removal and isolation of ill passengers and quarantine of non-ill passengers were implemented. By 20 February, 619 of 3,700 passengers and crew (17%) were tested positive.We estimated the basic reproduction number from the initial period of the outbreak using (SEIR) models. We calibrated the models with transient functions of countermeasures to incidence data. We additionally estimated a counterfactual scenario in absence of countermeasures, and established a model stratified by crew and guests to study the impact of differential contact rates among the groups. We also compared scenarios of an earlier versus later evacuation of the ship.The basic reproduction rate was initially 4 times higher on-board compared to the ${R}_0$ in the epicentre in Wuhan, but the countermeasures lowered it substantially. Based on the modeled initial ${R}_0$ of 14.8, we estimated that without any interventions within the time period of 21 January to 19 February, 2920 out of the 3700 (79%) would have been infected. Isolation and quarantine therefore prevented 2307 cases, and lowered the ${R}_0$ to 1.78. We showed that an early evacuation of all passengers on 3 February would have been associated with 76 infected persons in their incubation time.The cruise ship conditions clearly amplified an already highly transmissible disease. The public health measures prevented more than 2000 additional cases compared to no interventions. However, evacuating all passengers and crew early on in the outbreak would have prevented many more passengers and crew from infection.",2020,"Rocklöv, J.; Sjödin, H.; Wilder-Smith, A.",Journal of Travel Medicine,3006304371,#2926,True
e9239100c5493ea914dc23c3d7a262f4326022ac,CZI,Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection,10.1128/mBio.02764-19,,,cc-by,"Coronaviruses (CoVs) are common human and animal pathogens that can transmit zoonotically and cause severe respiratory disease syndromes. CoV infection requires spike proteins, which bind viruses to host cell receptors and catalyze virus-cell membrane fusion. Several CoV strains have spike proteins with two receptor-binding domains, an S1A that engages host sialic acids and an S1B that recognizes host transmembrane proteins. As this bivalent binding may enable broad zoonotic CoV infection, we aimed to identify roles for each receptor in distinct infection stages. Focusing on two betacoronaviruses, murine JHM-CoV and human Middle East respiratory syndrome coronavirus (MERS-CoV), we found that virus particle binding to cells was mediated by sialic acids; however, the transmembrane protein receptors were required for a subsequent virus infection. These results favored a two-step process in which viruses first adhere to sialic acids and then require subsequent engagement with protein receptors during infectious cell entry. However, sialic acids sufficiently facilitated the later stages of virus spread through cell-cell membrane fusion, without requiring protein receptors. This virus spread in the absence of the prototype protein receptors was increased by adaptive S1A mutations. Overall, these findings reveal roles for sialic acids in virus-cell binding, viral spike protein-directed cell-cell fusion, and resultant spread of CoV infections.IMPORTANCE CoVs can transmit from animals to humans to cause serious disease. This zoonotic transmission uses spike proteins, which bind CoVs to cells with two receptor-binding domains. Here, we identified the roles for the two binding processes in the CoV infection process. Binding to sialic acids promoted infection and also supported the intercellular expansion of CoV infections through syncytial development. Adaptive mutations in the sialic acid-binding spike domains increased the intercellular expansion process. These findings raise the possibility that the lectin-like properties of many CoVs contribute to facile zoonotic transmission and intercellular spread within infected organisms.",2020,"Qing, Enya; Hantak, Michael; Perlman, Stanley; Gallagher, Tom",mBio,3005811007,#2427,True
469ed0f00c09e2637351c9735c306f27acf3aace,CZI,First two months of the 2019 Coronavirus Disease (COVID-19) epidemic in China: real-time surveillance and evaluation with a second derivative model,10.1186/s41256-020-00137-4,,,cc-by,"Similar to outbreaks of many other infectious diseases, success in controlling the novel 2019 coronavirus infection requires a timely and accurate monitoring of the epidemic, particularly during its early period with rather limited data while the need for information increases explosively.",2020,"Chen, Xinguang; Yu, Bin",Global Health Research and Policy,3006645647,#5595,True
4e550e034ccca6fa2a91e481ddba24db67bc9ae5,CZI,Effectiveness of airport screening at detecting travellers infected with novel coronavirus (2019-nCoV),10.2807/1560-7917.ES.2020.25.5.2000080,,,cc-by,"We simulated 100 2019-nCoV infected travellers planning to board a flight who would pose a risk for seeding transmission in a new region. The duration of travel was considered as the flight time plus a small amount of additional travel time (ca 1 hour) for airport procedures. We assumed that infected individuals will develop symptoms, including fever, at the end of their incubation period (mean 5.2 days (Table)) [8] and progress to more severe symptoms after a few days, resulting in hospitalisation and isolation. We also took into account that individuals may have asymptomatic (subclinical) infection that would not be detected by thermal scanning or cause them to seek medical care, although these individuals may be infectious, and that infected travellers may exhibit severe symptoms during their travel and be hospitalised upon arrival without undergoing entry screening. We then estimated the proportion of infected travellers who would be detected by exit and entry screening, develop severe symptoms during travel, or go undetected, under varying assumptions of: (i) the duration of travel; (ii) the sensitivity of exit and entry screening; (iii) the proportion of asymptomatic infections; (iv) the incubation period and (v) the time from symptom onset to hospitalisation (Table).",2020,"Quilty, Billy J; Clifford, Sam; group2, CMMID nCoV working; Flasche, Stefan; Eggo, Rosalind M",Eurosurveillance,3005151538,#682,True
4bbb0c59babc718f67953fae032dad6ae0d7aeb1,CZI,Genome Detective Coronavirus Typing Tool for rapid identification and characterization of novel coronavirus genomes,10.1093/bioinformatics/btaa145,,32108862,cc-by-nc,"SUMMARY: Genome Detective is a web-based, user-friendly software application to quickly and accurately assemble all known virus genomes from next generation sequencing datasets. This application allows the identification of phylogenetic clusters and genotypes from assembled genomes in FASTA format. Since its release in 2019, we have produced a number of typing tools for emergent viruses that have caused large outbreaks, such as Zika and Yellow Fever Virus in Brazil. Here, we present The Genome Detective Coronavirus Typing Tool that can accurately identify the novel severe acute respiratory syndrome (SARS) related coronavirus (SARS-CoV-2) sequences isolated in China and around the world. The tool can accept up to 2,000 sequences per submission and the analysis of a new whole genome sequence will take approximately one minute. The tool has been tested and validated with hundreds of whole genomes from ten coronavirus species, and correctly classified all of the SARS-related coronavirus (SARSr-CoV) and all of the available public data for SARS-CoV-2. The tool also allows tracking of new viral mutations as the outbreak expands globally, which may help to accelerate the development of novel diagnostics, drugs and vaccines to stop the COVID-19 disease. AVAILABILITY: https://www.genomedetective.com/app/typingtool/cov. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.",2020,"Cleemput, S.; Dumon, W.; Fonseca, V.; Karim, W. A.; Giovanetti, M.; Alcantara, L. C.; Deforche, K.; de Oliveira, T.","Bioinformatics (Oxford, England)",3003548522,#2776,True
c821803c55c6aad89b6d0c1d3ba252051e464017,CZI,Case of the Index Patient Who Caused Tertiary Transmission of Coronavirus Disease 2019 in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Pneumonia Monitored by Quantitative RT-PCR,10.3346/jkms.2020.35.e79,,,cc-by-nc,"Since mid-December of 2019, coronavirus disease 2019 (COVID-19) has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, beta-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.",2020,"Lim, Jaegyun; Jeon, Seunghyun; Shin, Hyun-Young; Kim, Moon Jung; Seong, Yu Min; Lee, Wang Jun; Choe, Kang-Won; Kang, Yu Min; Lee, Baeckseung; Park, Sang-Joon",Journal of Korean Medical Science,3005657121,#3770,True
c3bee2a4caca614b34f92c17b643b854dcdab28d,CZI,Emergence of Novel Coronavirus 2019-nCoV: Need for Rapid Vaccine and Biologics Development,10.3390/pathogens9020148,,,cc-by,"Novel Coronavirus (2019-nCoV) is an emerging pathogen that was first identified in Wuhan, China in late December 2019. This virus is responsible for the ongoing outbreak that causes severe respiratory illness and pneumonia-like infection in humans. Due to the increasing number of cases in China and outside China, the WHO declared coronavirus as a global health emergency. Nearly 35,000 cases were reported and at least 24 other countries or territories have reported coronavirus cases as early on as February. Inter-human transmission was reported in a few countries, including the United States. Neither an effective anti-viral nor a vaccine is currently available to treat this infection. As the virus is a newly emerging pathogen, many questions remain unanswered regarding the virus’s reservoirs, pathogenesis, transmissibility, and much more is unknown. The collaborative efforts of researchers are needed to fill the knowledge gaps about this new virus, to develop the proper diagnostic tools, and effective treatment to combat this infection. Recent advancements in plant biotechnology proved that plants have the ability to produce vaccines or biopharmaceuticals rapidly in a short time. In this review, the outbreak of 2019-nCoV in China, the need for rapid vaccine development, and the potential of a plant system for biopharmaceutical development are discussed.",2020,"Shanmugaraj, Balamurugan; Malla, Ashwini; Phoolcharoen, Waranyoo",Pathogens,3003886061,#1502,True
715842fa536064980818ad7e31ce511272a4b6bc,CZI,The coronavirus 2019-nCoV epidemic: Is hindsight 20/20?,10.1016/j.eclinm.2020.100289,,,cc-by-nc-nd,,2020,"Malta, Monica; Rimoin, Anne W.; Strathdee, Steffanie A.",EClinicalMedicine,3004912618,#3333,True
601d3c7ae4ebcd2d835e9cf8d7427ebd0b5db83f,CZI,Nonstructural proteins NS7b and NS8 are likely to be phylogenetically associated with evolution of 2019-nCoV,10.1016/j.meegid.2020.104272,,,cc-by-nc-nd,"The seventh novel human infecting Betacoronavirus that causes pneumonia (2019 novel coronavirus, 2019-nCoV) originated in Wuhan, China. The evolutionary relationship between 2019-nCoV and the other human respiratory illness-causing coronavirus is not closely related. We sought to characterize the relationship of the translated proteins of 2019-nCoV with other species of Orthocoronavirinae. A phylogenetic tree was constructed from the genome sequences. A cluster tree was developed from the profiles retrieved from the presence and absence of homologs of ten 2019-nCoV proteins. The combined data were used to characterize the relationship of the translated proteins of 2019-nCoV to other species of Orthocoronavirinae. Our analysis reliably suggests that 2019-nCoV is most closely related to BatCoV RaTG13 and belongs to subgenus Sarbecovirus of Betacoronavirus, together with SARS coronavirus and Bat-SARS-like coronavirus. The phylogenetic profiling cluster of homolog proteins of one annotated 2019-nCoV protein against other genome sequences revealed two clades of ten 2019-nCoV proteins. Clade 1 consisted of a group of conserved proteins in Orthocoronavirinae comprising Orf1ab polyprotein, Nucleocapsid protein, Spike glycoprotein, and Membrane protein. Clade 2 comprised six proteins exclusive to Sarbecovirus and Hibecovirus. Two of six Clade 2 nonstructural proteins, NS7b and NS8, were exclusively conserved among 2019-nCoV, BetaCoV_RaTG, and BatSARS-like Cov. NS7b and NS8 have previously been shown to affect immune response signaling in the SARS-CoV experimental model. Thus, we speculated that knowledge of the functional changes in the NS7b and NS8 proteins during evolution may provide important information to explore the human infective property of 2019-nCoV.",2020,"Fahmi, Muhamad; Kubota, Yukihiko; Ito, Masahiro","Infection, Genetics and Evolution",2286137332,#4581,True
06c89f69aa7b5f9648d2c1543b8246fe9c3610cf,CZI,Pathogenicity and Transmissibility of 2019-nCoV—A Quick Overview and Comparison with Other Emerging Viruses,10.1016/j.micinf.2020.01.004,,,cc-by-nc-nd,"A zoonotic coronavirus, labeled as 2019-nCoV by The World Health Organization (WHO), has been identified as the causative agent of the viral pneumonia outbreak in Wuhan, China, at the end of 2019. Although 2019-nCoV can cause a severe respiratory illness like SARS and MERS, evidence from clinics suggested that 2019-nCoV is generally less pathogenic than SARS-CoV, and much less than MERS-CoV. The transmissibility of 2019-nCoV is still debated and needs to be further assessed. To avoid the 2019-nCoV outbreak turning into an epidemic or even a pandemic and to minimize the mortality rate, China activated emergency response procedures, but much remains to be learned about the features of the virus to refine the risk assessment and response. Here, the current knowledge in 2019-nCoV pathogenicity and transmissibility is summarized in comparison with several commonly known emerging viruses, and information urgently needed for a better control of the disease is highlighted.",2020,"Chen, Jieliang",Microbes and Infection,,#236,True
acb678bdd7634055de18d0b89bb6a4890e6a0306,CZI,Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro,10.1038/s41422-020-0282-0,,,cc-by,,2020,"Wang, Manli; Cao, Ruiyuan; Zhang, Leike; Yang, Xinglou; Liu, Jia; Xu, Mingyue; Shi, Zhengli; Hu, Zhihong; Zhong, Wu; Xiao, Gengfu",Cell Research,3005212621,#205,True
47772f3e98d8c61bb9782531a0338ba85f27bf3f,CZI,Potential for global spread of a novel coronavirus from China,10.1093/jtm/taaa011,,,cc-by-nc,,2020,"Bogoch, I. I.; Watts, A.; Thomas-Bachli, A.; Huber, C.; Kraemer, M. U. G.; Khan, K.",Journal of travel medicine,3004047749,#102,True
544a170a18bae9bf44c531c2b0b4bdc5e85ea8f5,CZI,Severe acute respiratory symptoms and suspected sars again 2020,10.12809/hkmj208375,,,cc-by-nc-nd,,2020,"Hon, K. L.; Leung, K. K. Y.",Hong Kong Medical Journal,2029408250,#3395,True
4ff89a71126d2932544a8337ba28787fde5f02a8,CZI,Statistics-Based Predictions of Coronavirus Epidemic Spreading in Mainland China,10.20535/ibb.2020.4.1.195074,,,cc-by,"Information about the open-access article 'Statistics-Based Predictions of Coronavirus Epidemic Spreading in Mainland China' in DOAJ. DOAJ is an online directory that indexes and provides access to quality open access, peer-reviewed journals.",2020,"Nesteruk, Igor",Innovative Biosystems and Bioengineering,3006304781,#1218,True
ac37ba61c91bb6939a507dbf4efe2119ddafeb9c,CZI,"Early transmission patterns of coronavirus disease 2019 (COVID-19) in travellers from Wuhan to Thailand, January 2020",10.2807/1560-7917.ES.2020.25.8.2000097,,,cc-by,,2020,"Okada, Pilailuk; Buathong, Rome; Phuygun, Siripaporn; Thanadachakul, Thanutsapa; Parnmen, Sittiporn; Wongboot, Warawan; Waicharoen, Sunthareeya; Wacharapluesadee, Supaporn; Uttayamakul, Sumonmal; Vachiraphan, Apichart; Chittaganpitch, Malinee; Mekha, Nanthawan; Janejai, Noppavan; Iamsirithaworn, Sopon; Lee, Raphael TC; Maurer-Stroh, Sebastian",Eurosurveillance,3005657121,#2582,True
6dfe2e77c8175b3eb38d6fc3ccc440fb81a0e2f0,CZI,HRCT Imaging Features in Representative Imported Cases of 2019 Novel Coronavirus Pneumonia,10.1093/pcmedi/pbaa004,,,cc-by-nc,"With the spread of novel coronavirus (2019-nCoV) pneumonia, chest high-resolution computed tomography (HRCT) has been one of the key diagnostic tools. To achieve early and accurate diagnostics, determining the radiological characteristics of the disease is of great importance. In this small scale research we retrospectively reviewed and selected six cases confirmed with 2019-nCoV infection in West China Hospital and investigated their initial and follow-up HRCT features, along with the clinical characteristics. The 2019-nCoV pneumonia basically showed a multifocal or unifocal involvement of ground-glass opacity (GGO), sometimes with consolidation and fibrosis. No pleural effusion or lymphadenopathy was identified in our presented cased. The follow-up CT generally demonstrated mild to moderate progression of the lesion, with only one case showing remission by the reducing extent and density of the airspace opacification.",2020,"Diao, Kaiyue; Han, Peilun; Pang, Tong; Li, Yuan; Yang, Zhigang",Precision Clinical Medicine,3006467527,#781,True
c9fee561c2a3834645dbb61dc4ae6448051da492,CZI,Comprehensive Genomic Characterization Analysis of lncRNAs in Cells With Porcine Delta Coronavirus Infection,10.3389/fmicb.2019.03036,,,cc-by,"Porcine delta coronavirus (PDCoV) is a novel emerging enterocytetropic virus causing diarrhea, vomiting, dehydration, and mortality in suckling piglets. Long non-coding RNAs (lncRNAs) are known to be important regulators during virus infection. Here, we describe a comprehensive transcriptome profile of lncRNA in PDCoV-infected swine testicular (ST) cells. In total, 1,308 annotated and 1,190 novel lncRNA candidate sequences were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these lncRNAs might be involved in numerous biological processes. Clustering analysis of differentially expressed lncRNAs showed that 454 annotated and 376 novel lncRNAs were regulated after PDCoV infection. Furthermore, we constructed a lncRNA-protein-coding gene co-expression interaction network. The KEGG analysis of the co-expressed genes showed that these differentially expressed lncRNAs were enriched in pathways related to metabolism and TNF signaling. Our study provided comprehensive information about lncRNAs that would be a useful resource for studying the pathogenesis of and designing antiviral therapy for PDCoV infection.",2020,"Liui, Junli; Wang, Fangfang; Du, Liuyang; Li, Juan; Yu, Tianqi; Jin, Yulan; Yan, Yan; Zhou, Jiyong; Gu, Jinyan",Frontiers in Microbiology,3003967510,#5462,True
655537fc8cc52bccf43cf7189ab060d3097caa7a,CZI,Potential Factors Influencing Repeated SARS Outbreaks in China,10.3390/ijerph17051633,,,cc-by,"Within last 17 years two widespread epidemics of severe acute respiratory syndrome (SARS) occurred in China, which were caused by related coronaviruses (CoVs): SARS-CoV and SARS-CoV-2. Although the origin(s) of these viruses are still unknown and their occurrences in nature are mysterious, some general patterns of their pathogenesis and epidemics are noticeable. Both viruses utilize the same receptor—angiotensin-converting enzyme 2 (ACE2)—for invading human bodies. Both epidemics occurred in cold dry winter seasons celebrated with major holidays, and started in regions where dietary consumption of wildlife is a fashion. Thus, if bats were the natural hosts of SARS-CoVs, cold temperature and low humidity in these times might provide conducive environmental conditions for prolonged viral survival in these regions concentrated with bats. The widespread existence of these bat-carried or -released viruses might have an easier time in breaking through human defenses when harsh winter makes human bodies more vulnerable. Once succeeding in making some initial human infections, spreading of the disease was made convenient with increased social gathering and holiday travel. These natural and social factors influenced the general progression and trajectory of the SARS epidemiology. However, some unique factors might also contribute to the origination of SARS in Wuhan. These factors are discussed in different scenarios in order to promote more research for achieving final validation.",2020,"Sun, Zhong; Thilakavathy, Karuppiah; Kumar, S. S.; He, Guozhong; Liu, V. Shi",International Journal of Environmental Research and Public Health,2615948593,#3296,True
bb7cd48a85b72f8d73e57d655c6d8a034fce3778,CZI,Puzzle of highly pathogenic human coronaviruses (2019-nCoV),10.1007/s13238-020-00693-y,,32088858,cc-by,,2020,"Li, Jing; Liu, Wenjun",Protein Cell,2766462213,#1815,True
3c42431c5b95e707486ce7441ac139071e07b706,CZI,RETRACTION: Retraction-Chinese medical staff request international medical assistance in fighting against COVID-19,10.1016/s2214-109x(20)30076-0,,32113504,cc-by,,2020,"The Editors Of The Lancet Global, Health",The Lancet. Global health,2794878804,#5486,False
6a93283b499ae5bc6aaf29f14e701dc8f25138ea,CZI,"Critical care response to a hospital outbreak of the 2019-nCoV infection in Shenzhen, China",10.1186/s13054-020-2786-x,,,cc-by,,2020,"Liu, Yong; Li, Jinxiu; Feng, Yongwen",Critical Care,2537200785,#1225,True
6fc52ed878c271020a2a375bb6e4b12943a7666c,CZI,Effectiveness for the Response to COVID-19: The MERS Outbreak Containment Procedures,10.24171/j.phrp.2020.11.1.01,,,cc-by-nc-nd,"In the current issue of Osong Public Health and Research Perspectives, 3 studies are presented dealing with COVID-19. A study by Kim et al, analyzed the genetic information of the COVID-19 virus isolated from a patient in South Korea. The virus was identified by real-time reverse transcriptase (RT) PCR followed by Next Generation Sequencing of the full-length of the genome [5]. In an interim report by the COVID-19 National Emergency Response Center of the KCDC, epidemiological and clinical characteristics of COVID-19 in 28 cases in South Korea were reported. There were 53.9% of cases who were males, with 16 cases in patients who had traveled abroad, of which 11 cases (39.3%) were from Wuhan, China, and 12 of the remaining cases were believed to have been infected in South Korea. The incubation period was 4.8 days. Most secondary infected cases were from family members outside the family home (66.7%) and within the family home (75%) [6].",2020,"Cho, Hae-Wol",Osong Public Health and Research Perspectives,3005887838,#2662,False
1d7f8850c5244fdc9b387038e7eeae9bcbbde6d2,CZI,Optimization Method for Forecasting Confirmed Cases of COVID-19 in China,10.3390/jcm9030674,,32131537,cc-by,"In December 2019, a novel coronavirus, called COVID-19, was discovered in Wuhan, China, and has spread to different cities in China as well as to 24 other countries. The number of confirmed cases is increasing daily and reached 34,598 on 8 February 2020. In the current study, we present a new forecasting model to estimate and forecast the number of confirmed cases of COVID-19 in the upcoming ten days based on the previously confirmed cases recorded in China. The proposed model is an improved adaptive neuro-fuzzy inference system (ANFIS) using an enhanced flower pollination algorithm (FPA) by using the salp swarm algorithm (SSA). In general, SSA is employed to improve FPA to avoid its drawbacks (i.e., getting trapped at the local optima). The main idea of the proposed model, called FPASSA-ANFIS, is to improve the performance of ANFIS by determining the parameters of ANFIS using FPASSA. The FPASSA-ANFIS model is evaluated using the World Health Organization (WHO) official data of the outbreak of the COVID-19 to forecast the confirmed cases of the upcoming ten days. More so, the FPASSA-ANFIS model is compared to several existing models, and it showed better performance in terms of Mean Absolute Percentage Error (MAPE), Root Mean Squared Relative Error (RMSRE), Root Mean Squared Relative Error (RMSRE), coefficient of determination ( R 2 ), and computing time. Furthermore, we tested the proposed model using two different datasets of weekly influenza confirmed cases in two countries, namely the USA and China. The outcomes also showed good performances.",2020,"Al-Qaness, Mohammed A. A.; Ewees, Ahmed A.; Fan, Hong; Abd El Aziz, Mohamed",J Clin Med,3006671704,#4638,True
f294f0df7468a8ac9e27776cc15fa20297a9f040,CZI,Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV,10.3390/v12020244,,,cc-by,"After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as “coronavirus disease 2019” (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms.",2020,"Xu, Jiabao; Zhao, Shizhe; Teng, Tieshan; Abdalla, Abualgasim Elgaili; Zhu, Wan; Xie, Longxiang; Wang, Yunlong; Guo, Xiangqian",Viruses,2163319355,#1449,True
60e51d3d13b027492b9f3b8693c58dd8b5385ada,CZI,"Novel coronavirus infection during the 2019–2020 epidemic: preparing intensive care units—the experience in Sichuan Province, China",10.1007/s00134-020-05954-2,,,cc-by-nc,"Novel coronavirus infection special intensive care team We set up a special emergency multi-disciplinary intensive care team to discuss the problems that we might encounter and countermeasures. Team members include intensive care unit (ICU) physician, infectious disease physician, nurse, respiratory therapist, nosocomial infection control expert, and administrative staff. We first evaluated the isolation conditions and the capacity of our department to admit a larger number of patients. Second, we specified the protection levels for different types of health care activities. Third, we assigned special work such as patient screening, consultation, and transfer to designated staff to minimize the number of health workers who had contact with patients with nCoV infection.ID - LiaoER -",2020,"Liao, Xuelian; Wang, Bo; Kang, Yan",Intensive Care Medicine,,#305,True
253cfd411f93ef88f702accd0fa195f24d1d2925,CZI,Return of the Coronavirus: 2019-nCoV,10.3390/v12020135,,,cc-by,"The emergence of a novel coronavirus (2019-nCoV) has awakened the echoes of SARS-CoV from nearly two decades ago. Yet, with technological advances and important lessons gained from previous outbreaks, perhaps the world is better equipped to deal with the most recent emergent group 2B coronavirus.",2020,"Gralinski, E. Lisa; Menachery, D. Vineet",Viruses,3002812395,#61,True
e7fbca71f16c3fbb78d754c95f24f58afc944c68,CZI,Application of the ARIMA model on the COVID-2019 epidemic dataset,10.1016/j.dib.2020.105340,,,cc-by-nc-nd,"Coronavirus disease 2019 (COVID-2019) has been recognized as a global threat, and several studies are being conducted using various mathematical models to predict the probable evolution of this epidemic. These mathematical models based on various factors and analyses are subject to potential bias. Here, we propose a simple econometric model that could be useful to predict the spread of COVID-2019. We performed Auto Regressive Integrated Moving Average (ARIMA) model prediction on the Johns Hopkins epidemiological data to predict the epidemiological trend of the prevalence and incidence of COVID-2019. For further comparison or for future perspective, case definition and data collection have to be maintained in real time.",2020,"Benvenuto, Domenico; Giovanetti, Marta; Vassallo, Lazzaro; Angeletti, Silvia; Ciccozzi, Massimo",Data in Brief,3002991745,#2363,True
c200af0e42a9aa8539b208d993015a75a2fe1151,CZI,Passengers' destinations from China: low risk of Novel Coronavirus (2019-nCoV) transmission into Africa and South America,10.1017/S0950268820000424,,32100667,cc-by,"Novel Coronavirus (2019-nCoV [SARS-COV-2]) was detected in humans during the last week of December 2019 at Wuhan city in China, and caused 24 554 cases in 27 countries and territories as of 5 February 2020. The objective of this study was to estimate the risk of transmission of 2019-nCoV through human passenger air flight from four major cities of China (Wuhan, Beijing, Shanghai and Guangzhou) to the passengers' destination countries. We extracted the weekly simulated passengers' end destination data for the period of 1-31 January 2020 from FLIRT, an online air travel dataset that uses information from 800 airlines to show the direct flight and passengers' end destination. We estimated a risk index of 2019-nCoV transmission based on the number of travellers to destination countries, weighted by the number of confirmed cases of the departed city reported by the World Health Organization (WHO). We ranked each country based on the risk index in four quantiles (4th quantile being the highest risk and 1st quantile being the lowest risk). During the period, 388 287 passengers were destined for 1297 airports in 168 countries or territories across the world. The risk index of 2019-nCoV among the countries had a very high correlation with the WHO-reported confirmed cases (0.97). According to our risk score classification, of the countries that reported at least one Coronavirus-infected pneumonia (COVID-19) case as of 5 February 2020, 24 countries were in the 4th quantile of the risk index, two in the 3rd quantile, one in the 2nd quantile and none in the 1st quantile. Outside China, countries with a higher risk of 2019-nCoV transmission are Thailand, Cambodia, Malaysia, Canada and the USA, all of which reported at least one case. In pan-Europe, UK, France, Russia, Germany and Italy; in North America, USA and Canada; in Oceania, Australia had high risk, all of them reported at least one case. In Africa and South America, the risk of transmission is very low with Ethiopia, South Africa, Egypt, Mauritius and Brazil showing a similar risk of transmission compared to the risk of any of the countries where at least one case is detected. The risk of transmission on 31 January 2020 was very high in neighbouring Asian countries, followed by Europe (UK, France, Russia and Germany), Oceania (Australia) and North America (USA and Canada). Increased public health response including early case recognition, isolation of identified case, contract tracing and targeted airport screening, public awareness and vigilance of health workers will help mitigate the force of further spread to naïve countries.",2020,"Haider, Najmul; Yavlinsky, Alexei; Simons, David; Osman, Abdinasir Yusuf; Ntoumi, Francine; Zumla, Alimuddin; Kock, Richard",Epidemiol Infect,3006028839,#2270,True
5734e3b81e16fe1976a129c5a0872716f3dd50b8,CZI,A new coronavirus associated with human respiratory disease in China,10.1038/s41586-020-2008-3,,32015508,cc-by,"Emerging infectious diseases, such as SARS and Zika, present a major threat to public health(1-3). Despite intense research efforts, how, when and where new diseases appear are still the source of considerable uncertainly. A severe respiratory disease was recently reported in the city Wuhan, Hubei province, China. Up to 25th of January 2020, at least 1,975 cases have been reported since the first patient was hospitalized on the 12th of December 2019. Epidemiological investigation suggested that the outbreak was associated with a seafood market in Wuhan. We studied one patient who was a worker at the market, and who was admitted to Wuhan Central Hospital on 26th of December 2019 experiencing a severe respiratory syndrome including fever, dizziness and cough. Metagenomic RNA sequencing(4) of a bronchoalveolar lavage fluid sample identified a novel RNA virus from the family Coronaviridae, designed here as WH-Human-1 coronavirus. Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) previously sampled from bats in China. This outbreak highlights the ongoing capacity of viral spill-over from animals to cause severe disease in humans.",2020,"Wu, Fan; Zhao, Su; Yu, Bin; Chen, Yan-Mei; Wang, Wen; Song, Zhi-Gang; Hu, Yi; Tao, Zhao-Wu; Tian, Jun-Hua; Pei, Yuan-Yuan; Yuan, Ming-Li; Zhang, Yu-Ling; Dai, Fa-Hui; Liu, Yi; Wang, Qi-Min; Zheng, Jiao-Jiao; Xu, Lin; Holmes, Edward C.; Zhang, Yong-Zhen",Nature,3003217347,#258,True
c2302facc633f9dfaf8597ffe57ca929e5d08b78,CZI,Moral imperative for the immediate release of 2019-nCoV sequence data,10.1093/nsr/nwaa030,,,cc-by,,2020,"Wu, Chung- I.; Poo, Mu-ming",National Science Review,2805337112,#1185,True
8819d114fe2dd2335a0545d53fea17deb6aa3943,CZI,Technical guidance for laboratory testing of 2019-nCoV infection (third edition),10.1016/j.bsheal.2020.02.001,,,cc-by-nc-nd,,2020,,Biosafety and Health,2992772421,#351,False
417cbe38a2f8a93d0827cd67f4c42076921d6050,CZI,Discovery and development of safe-in-man broad-spectrum antiviral agents,10.1016/j.ijid.2020.02.018,,,cc-by-nc-nd,"Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of general population from emerging and re-emerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 119 safe-in-man agents in freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.",2020,"Andersen, Petter I.; Ianevski, Aleksandr; Lysvand, Hilde; Vitkauskiene, Astra; Oksenych, Valentyn; Bjørås, Magnar; Telling, Kaidi; Lutsar, Irja; Dampis, Uga; Irie, Yasuhiko; Tenson, Tanel; Kantele, Anu; Kainov, Denis E.",International Journal of Infectious Diseases,2980655992,#1172,True
2892aee133b8b4037ace7ec6dfe6cab17e466292,CZI,"Li Wenliang, a face to the frontline healthcare worker? The first doctor to notify the emergence of the SARS-CoV-2, (COVID-19), outbreak",10.1016/j.ijid.2020.02.052,,,cc-by-nc-nd,,2020,"Petersen, Eskild; Hui, David; Hamer, Davidson H.; Blumberg, Lucille; Madoff, Lawrence C.; Pollack, Marjorie; Lee, Shui Shan; McLellan, Susan; Memish, Ziad; Praharaj, Ira; Wasserman, Sean; Ntoumi, Francine; Azhar, Esam Ibraheem; McHugh, Timothy D.; Kock, Richard; Ippolito, Guiseppe; Zumla, Ali; Koopmans, Marion",International Journal of Infectious Diseases,2600370084,#4474,True
6abb30ae61aa5e41f16a28b9437940d5d76d745b,CZI,"Phase-adjusted estimation of the number of Coronavirus Disease 2019 cases in Wuhan, China",10.1038/s41421-020-0148-0,,,cc-by,"An outbreak of clusters of viral pneumonia due to a novel coronavirus (2019-nCoV/SARS-CoV-2) happened in Wuhan, Hubei Province in China in December 2019. Since the outbreak, several groups reported estimated R0 of Coronavirus Disease 2019 (COVID-19) and generated valuable prediction for the early phase of this outbreak. After implementation of strict prevention and control measures in China, new estimation is needed. An infectious disease dynamics SEIR (Susceptible, Exposed, Infectious, and Removed) model was applied to estimate the epidemic trend in Wuhan, China under two assumptions of Rt. In the first assumption, Rt was assumed to maintain over 1. The estimated number of infections would continue to increase throughout February without any indication of dropping with Rt = 1.9, 2.6, or 3.1. The number of infections would reach 11,044, 70,258, and 227,989, respectively, by 29 February 2020. In the second assumption, Rt was assumed to gradually decrease at different phases from high level of transmission (Rt = 3.1, 2.6, and 1.9) to below 1 (Rt = 0.9 or 0.5) owing to increasingly implemented public health intervention. Several phases were divided by the dates when various levels of prevention and control measures were taken in effect in Wuhan. The estimated number of infections would reach the peak in late February, which is 58,077–84,520 or 55,869–81,393. Whether or not the peak of the number of infections would occur in February 2020 may be an important index for evaluating the sufficiency of the current measures taken in China. Regardless of the occurrence of the peak, the currently strict measures in Wuhan should be continuously implemented and necessary strict public health measures should be applied in other locations in China with high number of COVID-19 cases, in order to reduce Rt to an ideal level and control the infection.",2020,"Wang, Huwen; Wang, Zezhou; Dong, Yinqiao; Chang, Ruijie; Xu, Chen; Yu, Xiaoyue; Zhang, Shuxian; Tsamlag, Lhakpa; Shang, Meili; Huang, Jinyan; Wang, Ying; Xu, Gang; Shen, Tian; Zhang, Xinxin; Cai, Yong",Cell Discovery,3004397688,#1750,True
6d16e166279a7d116a78a21d4bd4c00b505a617e,CZI,The reproductive number of COVID-19 is higher compared to SARS coronavirus,10.1093/jtm/taaa021,,,cc-by-nc,"Teaser: Our review found the average R0 for 2019-nCoV to be 3.28, which exceeds WHO estimates of 1.4 to 2.5.Here we review the basic reproduction number (R0) of the 2019-nCoV virus. R0 is an indication of the transmissibility of a virus, representing the average number of new infections generated by an infectious person in a totally naïve population. For R0 greater than one the number infected is likely to increase, and for R0 less than one transmission is likely to die out. The basic reproduction number is a central concept in infectious disease epidemiology, indicating the risk of an infectious agent with respect to epidemic spread.",2020,"Liu, Ying; Gayle, Albert A.; Wilder-Smith, Annelies; Rocklöv, Joacim",Journal of Travel Medicine,3006642361,#852,True
5423004ce74c612a32c8ff24b3f161eb92a62979,CZI,"Middle East respiratory syndrome coronavirus (MERS-CoV) neutralising antibodies in a high-risk human population, Morocco, November 2017 to January 2018",10.2807/1560-7917.ES.2019.24.48.1900244,,,cc-by,,2019,"Abbad, Anass; Perera, Ranawaka APM; Anga, Latifa; Faouzi, Abdellah; Minh, Nhu Nguyen Tran; Malik, Sk Md Mamunur Rahman; Iounes, Nadia; Maaroufi, Abderrahmane; Kerkhove, Maria D Van; Peiris, Malik; Nourlil, Jalal",Eurosurveillance,2991640369,#3502,True
779c1b5cb3afe3d50219aa2af791014a22eb355a,CZI,"Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections",10.3390/v12020194,,,cc-by,"In early December 2019 a cluster of cases of pneumonia of unknown cause was identified in Wuhan, a city of 11 million persons in the People’s Republic of China. Further investigation revealed these cases to result from infection with a newly identified coronavirus, termed the 2019-nCoV. The infection moved rapidly through China, spread to Thailand and Japan, extended into adjacent countries through infected persons travelling by air, eventually reaching multiple countries and continents. Similar to such other coronaviruses as those causing the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), the new coronavirus was reported to spread via natural aerosols from human-to-human. In the early stages of this epidemic the case fatality rate is estimated to be approximately 2%, with the majority of deaths occurring in special populations. Unfortunately, there is limited experience with coronavirus infections during pregnancy, and it now appears certain that pregnant women have become infected during the present 2019-nCoV epidemic. In order to assess the potential of the Wuhan 2019-nCoV to cause maternal, fetal and neonatal morbidity and other poor obstetrical outcomes, this communication reviews the published data addressing the epidemiological and clinical effects of SARS, MERS, and other coronavirus infections on pregnant women and their infants. Recommendations are also made for the consideration of pregnant women in the design, clinical trials, and implementation of future 2019-nCoV vaccines.",2020,"Schwartz, David A.; Graham, Ashley L.",Viruses,3004581842,#590,True
355f8c97211726732a20ce50da8b11ffdf3303ab,CZI,"Laboratory readiness and response for novel coronavirus (2019-nCoV) in expert laboratories in 30 EU/EEA countries, January 2020",10.2807/1560-7917.ES.2020.25.6.2000082,,,cc-by,"Timely detection of novel coronavirus (2019-nCoV) infection cases is crucial to interrupt the spread of this virus. We assessed the required expertise and capacity for molecular detection of 2019-nCoV in specialised laboratories in 30 European Union/European Economic Area (EU/EEA) countries. Thirty-eight laboratories in 24 EU/EEA countries had diagnostic tests available by 29 January 2020. A coverage of all EU/EEA countries was expected by mid-February. Availability of primers/probes, positive controls and personnel were main implementation barriers.",2020,"Reusken, Chantal B.E.M.; Broberg, Eeva K.; Haagmans, Bart; Meijer, Adam; Corman, Victor M.; Papa, Anna; Charrel, Remi; Drosten, Christian; Koopmans, Marion; Leitmeyer, Katrin",Eurosurveillance,3006255311,#664,False
cb0831902de1f8a19992ff86bcc7e15fa2d7d687,CZI,"Initial Cluster of Novel Coronavirus (2019-nCoV) Infections in Wuhan, China Is Consistent with Substantial Human-to-Human Transmission",10.3390/jcm9020488,,32054045,cc-by,"Reanalysis of the epidemic curve from the initial cluster of cases with novel coronavirus (2019-nCoV) in December 2019 indicates substantial human-to-human transmission. It is possible that the common exposure history at a seafood market in Wuhan originated from the human-to-human transmission events within the market, and the early, strong emphasis that market exposure indicated animal-to-human transmission was potentially the result of observer bias. To support the hypothesis of zoonotic origin of 2019-nCoV stemming from the Huanan seafood market, the index case should have had exposure history related to the market and the virus should have been identified from animals sold at the market. As these requirements remain unmet, zoonotic spillover at the market must not be overemphasized.",2020,"Nishiura, Hiroshi; Linton, Natalie M.; Akhmetzhanov, Andrei R.",J Clin Med,3005599914,#933,True
cef8a948bad454c49e10e6aed8c0cb2ce3215c62,CZI,Potential association between COVID-19 mortality and health-care resource availability,10.1016/S2214-109X(20)30068-1,,,cc-by-nc-nd,"As recorded by the Chinese Center for Disease Control and Prevention (China CDC), by Feb 16, 2020, there had been 70 641 confirmed cases and 1772 deaths due to COVID-19, with an average mortality of about 2·5%. However, in-depth analysis of these data show clear disparities in mortality rates between Wuhan (>3%), different regions of Hubei (about 2·9% on average), and across the other provinces of China (about 0·7% on average). We postulate that this is likely to be related to the rapid escalation in the number of infections around the epicentre of the outbreak, which has resulted in an insufficiency of health-care resources, thereby negatively affecting patient outcomes in Hubei, while this has not yet been the situation for the other parts of China (figure A, B). If we assume that average levels of health care are similar throughout China, higher numbers of infections in a given population can be considered an indirect indicator of a heavier health-care burden. Plotting mortality against the incidence of COVID-19 (cumulative number of confirmed cases since the start of the outbreak, per 10 000 population) showed a significant positive correlation (figure C), suggesting that mortality is correlated with health-care burden.",,"Ji, Yunpeng; Ma, Zhongren; Peppelenbosch, Maikel P.; Pan, Qiuwei",The Lancet Global Health,2343822881,#1979,False
4af62711ee4cca0c90baf73be3e83ea95e68c045,CZI,Estimation of the reproductive number of Novel Coronavirus (COVID-19) and the probable outbreak size on the Diamond Princess cruise ship: A data-driven analysis,10.1016/j.ijid.2020.02.033,,,cc-by-nc-nd,"Backgrounds Up to February 16, 2020, 355 cases have been confirmed as having COVID-19 infection on the Diamond Princess cruise ship. It is of crucial importance to estimate the reproductive number (R0) of the novel virus in the early stage of outbreak and make a prediction of daily new cases on the ship. Method We fitted the reported serial interval (Mean and standard deviation) with a gamma distribution and applied “earlyR” package in R to estimate the R0 in the early stage of COVID-19 outbreak. We applied “projections” package in R to simulate the plausible cumulative epidemic trajectories and future daily incidence by fitting the data of existing daily incidence, a serial interval distribution, and the estimated R0 into a model based on the assumption that daily incidence obeys approximately Poisson distribution determined by daily infectiousness. Results The Maximum-Likelihood (ML) value of R0 was 2.28 for COVID-19 outbreak at early stage on the ship. The median with 95% confidence interval (CI) of R0 values was 2.28 (2.06-2.52) estimated by the bootstrap resampling method. The probable number of new cases for the next ten days would gradually increase, and the estimated cumulative cases would reach 1514 (1384-1656) at the tenth day in the future. However, if R0 value was reduced by 25% and 50%, the estimated total number of cumulative cases would be reduced to 1081 (981-1177) and 758 (697-817), respectively. Conclusion The median with 95% CI of R0 of COVID-19 was about 2.28 (2.06-2.52) during the early stage experienced on the Diamond Princess cruise ship. The future daily incidence and probable outbreak size is largely dependent on the change of R0. Unless strict infection management and control are taken, our findings indicate the potential of COVID-19 to cause greater outbreak on the ship.",2020,"Zhang, Sheng; Diao, MengYuan; Yu, Wenbo; Pei, Lei; Lin, Zhaofen; Chen, Dechang",International Journal of Infectious Diseases,3001305894,#1430,True
83c96f2a481be06a5c58552cbad2ca67ce789dc2,CZI,Identification of COVID-19 Can be Quicker through Artificial Intelligence framework using a Mobile Phone-Based Survey in the Populations when Cities/Towns Are Under Quarantine,10.1017/ice.2020.61,,,cc-by,We are proposing to use machine learning algorithms to be able to improve possible case identifications of COVID-19 more quicker when we use a mobile phone-based web survey. This will also reduce the spread in the susceptible populations.,2020,"Vazquez, Arni S.R. Srinivasa Rao; Jose A.",Infection Control & Hospital Epidemiology,2816053183,#3078,True
b0f4f2cb1c392ec68afaa865ecdd5db824ccf457,CZI,Nepal’s First Case of COVID-19 and public health response,10.1093/jtm/taaa024,,,cc-by-nc,"SARS, in 2003, spread both within a geographical region and, more significantly, to different cities from a single location, through infected travelers.4 The air-travel frequency from major cities in China to Nepal is lower compared to that of other countries.5 However, there are other factors to consider. Firstly, Nepal is an emerging tourist destination and 2020 has been declared “Visit Nepal” year with an expected 500,000 tourists. Among the total number of tourists in 2018, 153633, the second-highest number, were Chinese tourists, with the highest influx during February and December.6 COVID-19 outbreak coincides (similar to SARS) with Chinese new year during which the Chinese travel extensively, increasing chances for transmission.7 Study into coronavirus infections in Nepal, has shown the incidence to be higher in winter (DecemberFebruary).8 Furthermore, Nepal shares northern border with China with several border crossing points. Several Nepalese students study in China and in Wuhan, the epicenter of the outbreak. Thus, the potential for the spread of COVID-19 through travel and the overlap between the months of peak tourist season in Nepal and the months of the emergence of the epidemic could pose a risk to Nepal. One confirmed case in Nepal was a Nepalese student, studying in Wuhan, with symptom-onset on January 3. The infected 32-year-old male had returned on January 9 to spend winter holidays in Nepal. He had prior knowledge about the outbreak in China and visited the Sukraraj Tropical (truncated)",2020,"Shrestha, Ranish; Shrestha, Sunil; Khanal, Pratik; Bhuvan, K. C.",Journal of Travel Medicine,,#2547,True
ecd8df7900c3c07863a0ed0e1b6c5d5ecae4e651,CZI,Comparative Serological Study for the Prevalence of Anti-MERS Coronavirus Antibodies in High- and Low-Risk Groups in Qatar,10.1155/2019/1386740,,134769660,cc-by,"Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) could be asymptomatic or cause mild influenza-like illness. Therefore, the prevalence of MERS-CoV infections in the general population could be underestimated, which necessitates active surveillance to determine the epidemiological importance of asymptomatic cases. The aim of this study is to evaluate the performance of various serological assays and to estimate the seroprevalence of anti-MERS-CoV antibodies in high- and low-risk groups in Qatar. A total of 4858 samples were screened, including 4719 samples collected from healthy blood donors (BD) over a period of five years (2012-2016), 135 samples from baseline case contacts (CC) collected from individuals in close contact with three positive PCR-confirmed patients (CP), and four samples from MERS-CoV CP. Initial screening using anti-MERS-CoV IgG (IgG rS1-ELISA kit) revealed ten reactive samples from BD (10/4719, 0.21%), one from CC (1/135, 0.74%), and three from CP (3/4, 75%). Samples from CP but not from BD were also reactive by whole-virus anti-MERS-CoV IgG (n = 3/4) and IgM (n = 1/4) indirect immunefluorescent tests (IIFT) and pseudoparticle neutralization test (ppNT). The reactive sample from CC was also confirmed by ppNT. Surprisingly, one out of thirteen (7.7%) randomly selected IgG rS1-ELISA-negative BD samples from the initial screening was reactive by the IgM-IIFT (but not by the IgG-IIFT) and was subsequently confirmed by ppNT. All IgG rS1-ELISA-reactive samples from BD exhibited considerable reactivity to the four circulating human coronaviruses (HKU1, OC43, 229E, and NL63). Cross-reactivity with SARS was only reported for samples from CP using IgG and IgM-IIFT. In conclusion, we report a low prevalence of anti-MERS antibodies in the general population, which coincides with the low number of all reported cases by the time of our study (2017) in Qatar (n = 21). The false-positive results and the observed cross-reactivity between MERS-CoV and other circulating human coronavirus necessitate more detailed evaluation of available serological assays.",2019,"Al Kahlout, Reham A.; Nasrallah, Gheyath K.; Farag, Elmoubasher A.; Wang, Lingshu; Lattwein, Erik; Müller, Marcel A.; El Zowalaty, Mohamed E.; Al Romaihi, Hamad E.; Graham, Barney S.; Al Thani, Asmaa A.; Yassine, Hadi M.",Journal of Immunology Research,2913478568,#2447,True
4a077b9696d19b7d7fa3e71560b7fd5f414a4d19,CZI,"Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020",10.2807/1560-7917.ES.2020.25.5.2000062,,,cc-by,"In January 2020, an increasing number of cases confirmed to be infected with 2019-nCoV were detected outside Wuhan. For 88 cases detected between 20 and 28 January, the travel history (to and) from Wuhan is known, as well as their symptom onset date. Their ages range from 2 to 72 years of age (information missing for four cases); 31 were female and 57 were male. During this initial stage of the epidemic, it is most likely that these travellers were infected in Wuhan. Consequently, their time spent in Wuhan can be taken as the duration of exposure to infection. Of these 88 cases with known travel history, 63 were Wuhan residents who travelled elsewhere and 25 were visitors who stayed in Wuhan for a limited time. By taking the date of symptom onset and travel history together, we inferred the possible incubation period for each of these cases. The data used for this analysis has been translated from Chinese sources such as provincial centres of disease control, and made publicly available [8]. We took the data as available on 29 January 2020 (Supplementary Material S1).",2020,"Backer, Jantien A; Klinkenberg, Don; Wallinga, Jacco",Eurosurveillance,,#668,True
0938d2fb07611897abf38cea727ddbeea77b73d9,CZI,Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess,10.3390/jcm9030657,,32121356,cc-by,"To understand the time-dependent risk of infection on a cruise ship, the Diamond Princess, I estimated the incidence of infection with novel coronavirus (COVID-19). The epidemic curve of a total of 199 confirmed cases was drawn, classifying individuals into passengers with and without close contact and crew members. A backcalculation method was employed to estimate the incidence of infection. The peak time of infection was seen for the time period from 2 to 4 February 2020, and the incidence has abruptly declined afterwards. The estimated number of new infections among passengers without close contact was very small from 5 February on which a movement restriction policy was imposed. Without the intervention from 5 February, it was predicted that the cumulative incidence with and without close contact would have been as large as 1373 (95% CI: 570, 2176) and 766 (95% CI: 587, 946) cases, respectively, while these were kept to be 102 and 47 cases, respectively. Based on an analysis of illness onset data on board, the risk of infection among passengers without close contact was considered to be very limited. Movement restriction greatly reduced the number of infections from 5 February onwards.",2020,"Nishiura, Hiroshi",J Clin Med,3005847234,#3329,True
09de57e5401565a1e80361d32b09ce66b3a988c8,CZI,Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies,10.3390/v12030254,,,cc-by,"The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.",2020,"Ahmed, F. Syed; Quadeer, A. Ahmed; McKay, R. Matthew",Viruses,3005472135,#2017,True
6e5ed49cd3824f3c7c435bf91302ad07f979dece,CZI,Frontiers in antiviral therapy and immunotherapy,10.1002/cti2.1115,,,cc-by,,2020,"Heaton, Steven M",Clinical & Translational Immunology,2956917138,#1302,False
0f34f180295196b73c5bf7c4892fb023d388cb15,CZI,2019-nCoV in context: lessons learned?,10.1016/S2542-5196(20)30035-8,,,cc-by,,2020,"Kock, Richard A.; Karesh, William B.; Veas, Francisco; Velavan, Thirumalaisamy P.; Simons, David; Mboera, Leonard E. G.; Dar, Osman; Arruda, Liã Bárbara; Zumla, Alimuddin",The Lancet Planetary Health,3004999328,#513,True
d4b843968ab01451c9553576eff63a52ad8ba9a4,CZI,Serial interval of novel coronavirus (COVID-19) infections,10.1016/j.ijid.2020.02.060,,,cc-by-nc-nd,"Objective To estimate the serial interval of novel coronavirus (COVID-19) from information on 28 infector-infectee pairs. Methods We collected dates of illness onset for primary cases (infectors) and secondary cases (infectees) from published research articles and case investigation reports. We subjectively ranked the credibility of the data and performed analyses on both the full dataset (n = 28) and a subset of pairs with highest certainty in reporting (n = 18). In addition, we adjust for right truncation of the data as the epidemic is still in its growth phase. Results Accounting for right truncation and analyzing all pairs, we estimated the median serial interval at 4.0 days (95% credible interval [CrI]: 3.1, 4.9). Limiting our data to only the most certain pairs, the median serial interval was estimated at 4.6 days (95% CrI: 3.5, 5.9). Conclusions The serial interval of COVID-19 is close to or shorter than its median incubation period. This suggests that a substantial proportion of secondary transmission may occur prior to illness onset. The COVID-19 serial interval is also shorter than the serial interval of severe acute respiratory syndrome (SARS), indicating that calculations made using the SARS serial interval may introduce bias.",2020,"Nishiura, Hiroshi; Linton, Natalie M.; Akhmetzhanov, Andrei R.",International Journal of Infectious Diseases,3004658686,#4488,True
43ac139b156b7a9397d9da995694319fdeeba0f4,CZI,Recommended psychological crisis intervention response to the 2019 novel coronavirus pneumonia outbreak in China: a model of West China Hospital,10.1093/pcmedi/pbaa006,,,cc-by-nc,"The novel coronavirus pneumonia (COVID-19)epidemic has brought serious social psychological impact to the Chinese people, especially those quarantined and thus with limited access to face-to-face communication and traditional social psychological interventions. To better deal with the urgent psychological problems of people involved in the COVID-19 epidemic, we developed a new psychological crisis intervention model by utilizing internet technology. This new model, one of West China Hospital, integrates physicians, psychiatrists, psychologists and social workers into Internet platforms to carry out psychological intervention to patients, their families and medical staff. We hope this model will make a sound basis for developing a more comprehensive psychological crisis intervention response system that is applicable for urgent social and psychological problems.",2020,"Zhang, Jun; Wu, Weili; Zhao, Xin; Zhang, Wei",Precision Clinical Medicine,3003487504,#1181,True
ebfc471829e1303889bd23779d1c2ffb9467ab7e,CZI,Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province,10.1097/CM9.0000000000000744,,32044814,cc-by-nc-nd,"BACKGROUND: A novel coronavirus (2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and analyzed the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak. METHODS: Clinical data from 137 2019-nCoV-infected patients admitted to the respiratory departments of nine tertiary hospitals in Hubei province from December 30, 2019 to January 24, 2020 were collected, including general status, clinical manifestations, laboratory test results, imaging characteristics, and treatment regimens. RESULTS: None of the 137 patients (61 males, 76 females, aged 20-83 years, mean age 55 ± 16 years) had a definite history of exposure to Huanan Seafood Wholesale Market. Major initial symptoms included fever (112/137, 81.8%), coughing (66/137, 48.2%), and muscle pain or fatigue (44/137, 32.1%), with other, less typical initial symptoms observed at low frequency, including heart palpitations, diarrhea, and headache. Nearly 80% of the patients had normal or decreased white blood cell counts, and 72.3% (99/137) had lymphocytopenia. Lung involvement was present in all cases, with most chest computed tomography scans showing lesions in multiple lung lobes, some of which were dense; ground-glass opacity co-existed with consolidation shadows or cord-like shadows. Given the lack of effective drugs, treatment focused on symptomatic and respiratory support. Immunoglobulin G was delivered to some critically ill patients according to their condition. Systemic corticosteroid treatment did not show significant benefits. Notably, early respiratory support facilitated disease recovery and improved prognosis. The risk of death was primarily associated with age, underlying chronic diseases, and median interval from the appearance of initial symptoms to dyspnea. CONCLUSIONS: The majority of patients with 2019-nCoV coronavirus pneumonia present with fever as the first symptom, and most of them still showed typical manifestations of viral pneumonia on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.",2020,"Kui, Liu; Fang, Yuan-Yuan; Deng, Yan; Liu, Wei; Wang, Mei-Fang; Ma, Jing-Ping; Xiao, Wei; Wang, Ying-Nan; Zhong, Min-Hua; Li, Cheng-Hong; Li, Guang-Cai; Liu, Hui-Guo",Chin Med J (Engl),3006485704,#691,True
b70d27459fd8143edf76721da40cdbca399c9fb1,CZI,Science in the fight against the novel coronavirus disease,10.1097/CM9.0000000000000777,,32118642,cc-by-nc-nd,,2020,"Wang, Jian-Wei; Cao, Bin; Wang, Chen",Chin Med J (Engl),2120794924,#3282,True
9ec258353291e981ef7eeb36111794c40b15c752,CZI,The outbreak of COVID-19: An overview,10.1097/jcma.0000000000000270,,32134861,cc-by-nc-nd,"In late December 2019, a previous unidentified coronavirus, currently named as the 2019 novel coronavirus#, emerged from Wuhan, China, and resulted in a formidable outbreak in many cities in China and expanded globally, including Thailand, Republic of Korea, Japan, United States, Philippines, Viet Nam, and our country (as of 2/6/2020 at least 25 countries). The disease is officially named as Coronavirus Disease-2019 (COVID-19, by WHO on February 11, 2020). It is also named as Severe Pneumonia with Novel Pathogens on January 15, 2019 by the Taiwan CDC, the Ministry of Health and is a notifiable communicable disease of the fifth category. COVID-19 is a potential zoonotic disease with low to moderate (estimated 2%-5%) mortality rate. Person-to-person transmission may occur through droplet or contact transmission and if there is a lack of stringent infection control or if no proper personal protective equipment available, it may jeopardize the first-line healthcare workers. Currently, there is no definite treatment for COVID-19 although some drugs are under investigation. To promptly identify patients and prevent further spreading, physicians should be aware of the travel or contact history of the patient with compatible symptoms.",2020,"Wu, Y. C.; Chen, C. S.; Chan, Y. J.",Journal of the Chinese Medical Association : JCMA,1757890151,#5321,True
ead6fda7cdb2bb2469ff48365833bd63d0b7dd1a,CZI,Estimation of the Transmission Risk of the 2019-nCoV and Its Implication for Public Health Interventions,10.3390/jcm9020462,,,cc-by,"Since the emergence of the first cases in Wuhan, China, the novel coronavirus (2019-nCoV) infection has been quickly spreading out to other provinces and neighboring countries. Estimation of the basic reproduction number by means of mathematical modeling can be helpful for determining the potential and severity of an outbreak and providing critical information for identifying the type of disease interventions and intensity. A deterministic compartmental model was devised based on the clinical progression of the disease, epidemiological status of the individuals, and intervention measures. The estimations based on likelihood and model analysis show that the control reproduction number may be as high as 6.47 (95% CI 5.71–7.23). Sensitivity analyses show that interventions, such as intensive contact tracing followed by quarantine and isolation, can effectively reduce the control reproduction number and transmission risk, with the effect of travel restriction adopted by Wuhan on 2019-nCoV infection in Beijing being almost equivalent to increasing quarantine by a 100 thousand baseline value. It is essential to assess how the expensive, resource-intensive measures implemented by the Chinese authorities can contribute to the prevention and control of the 2019-nCoV infection, and how long they should be maintained. Under the most restrictive measures, the outbreak is expected to peak within two weeks (since 23 January 2020) with a significant low peak value. With travel restriction (no imported exposed individuals to Beijing), the number of infected individuals in seven days will decrease by 91.14% in Beijing, compared with the scenario of no travel restriction.",2020,"Tang, Biao; Wang, Xia; Li, Qian; Bragazzi, Nicola Luigi; Tang, Sanyi; Xiao, Yanni; Wu, Jianhong",Journal of Clinical Medicine,3003403425,#535,True
a14b5655cb13ed64cb8cff7c806a7b58c858b8b7,CZI,Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts,10.1016/S2214-109X(20)30074-7,,,cc-by-nc-nd,"Summary Background Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19. Methods We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R0), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort. Findings Simulated outbreaks starting with five initial cases, an R0 of 1·5, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R0 was 2·5 or 3·5 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R0 of 1·5 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R0 of 2·5 more than 70% of contacts had to be traced, and for an R0 of 3·5 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R0 was 1·5. For R0 values of 2·5 or 3·5, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset. Interpretation In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts. Funding Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.",2020,"Hellewell, Joel; Abbott, Sam; Gimma, Amy; Bosse, Nikos I.; Jarvis, Christopher I.; Russell, Timothy W.; Munday, James D.; Kucharski, Adam J.; Edmunds, W. John; Sun, Fiona; Flasche, Stefan; Quilty, Billy J.; Davies, Nicholas; Liu, Yang; Clifford, Samuel; Klepac, Petra; Jit, Mark; Diamond, Charlie; Gibbs, Hamish; van Zandvoort, Kevin; Funk, Sebastian; Eggo, Rosalind M.",The Lancet Global Health,3005722800,#2829,True
00e5a723d44eb9f2698c38b518eff85c00f9753b,CZI,Six weeks into the 2019 coronavirus disease (COVID-19) outbreak- it is time to consider strategies to impede the emergence of new zoonotic infections,10.1097/CM9.0000000000000760,,32097202,cc-by-nc-nd,,2020,"Harypursat, Vijay; Chen, Yao-Kai",Chin Med J (Engl),3005943294,#1985,True
fbf7b36a98caf3fa41ff9f011dbc9eec0d02609d,CZI,La comunicación científica y el acceso abierto en la contención de enfermedades: El caso del Coronavirus novel 2019 (2019-nCoV),10.35839/repis.4.1.613,,,cc-by-nc,,2020,"Arteaga-Livias, Franz K.; Rodriguez-Morales, Alfonso J.",Revista Peruana de Investigación en Salud,,#346,True
fd28e6d03eef27b0454f13ca539dc1498242a4c2,CZI,A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version),10.1186/s40779-020-0233-6,,,cc-by,"In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named “2019 novel coronavirus (2019-nCoV)” by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.",2020,"Jin, Ying-Hui; Cai, Lin; Cheng, Zhen-Shun; Cheng, Hong; Deng, Tong; Fan, Yi-Pin; Fang, Cheng; Huang, Di; Huang, Lu-Qi; Huang, Qiao; Han, Yong; Hu, Bo; Hu, Fen; Li, Bing-Hui; Li, Yi-Rong; Liang, Ke; Lin, Li-Kai; Luo, Li-Sha; Ma, Jing; Ma, Lin-Lu; Peng, Zhi-Yong; Pan, Yun-Bao; Pan, Zhen-Yu; Ren, Xue-Qun; Sun, Hui-Min; Wang, Ying; Wang, Yun-Yun; Weng, Hong; Wei, Chao-Jie; Wu, Dong-Fang; Xia, Jian; Xiong, Yong; Xu, Hai-Bo; Yao, Xiao-Mei; Yuan, Yu-Feng; Ye, Tai-Sheng; Zhang, Xiao-Chun; Zhang, Ying-Wen; Zhang, Yin-Gao; Zhang, Hua-Min; Zhao, Yan; Zhao, Ming-Juan; Zi, Hao; Zeng, Xian-Tao; Wang, Yong-Yan; Wang, Xing-Huan; Management, for the Zhongnan Hospital of Wuhan University Novel Coronavirus; Research Team, Evidence-Based Medicine Chapter of China International Exchange; Promotive Association for, Medical; Health, Care",Military Medical Research,3004824173,#405,True
7b7c71218f8d7ea1a1f8f702e4262b839bf7cc8a,CZI,Outbreak of Novel Coronavirus (SARS-Cov-2): First Evidences From International Scientific Literature and Pending Questions,10.3390/healthcare8010051,,32120965,cc-by,"On 31 December, 2019, a cluster of 27 pneumonia cases of unknown etiology was reported by Chinese health authorities in Wuhan City (China) [...].",2020,"Amodio, Emanuele; Vitale, Francesco; Cimino, Livia; Casuccio, Alessandra; Tramuto, Fabio",Healthcare (Basel),3005538648,#3464,True
823305045f63acc52d90c2a299b25fc8f4ebe587,CZI,"Epidemiological Identification of A Novel Pathogen in Real Time: Analysis of the Atypical Pneumonia Outbreak in Wuhan, China, 2019-2020",10.3390/jcm9030637,,32120913,cc-by,"Virological tests have now shown conclusively that a novel coronavirus is causing the 2019-2020 atypical pneumonia outbreak in Wuhan, China. We demonstrate that non-virological descriptive characteristics could have determined that the outbreak is caused by a novel pathogen in advance of virological testing. Characteristics of the ongoing outbreak were collected in real time from two medical social media sites. These were compared against characteristics of eleven pathogens that have previously caused cases of atypical pneumonia. The probability that the current outbreak is due to ""Disease X"" (i.e., previously unknown etiology) as opposed to one of the known pathogens was inferred, and this estimate was updated as the outbreak continued. The probability (expressed as a percentage) that Disease X is driving the outbreak was assessed as over 29% on 31 December 2019, one week before virus identification. After some specific pathogens were ruled out by laboratory tests on 5 January 2020, the inferred probability of Disease X was over 49%. We showed quantitatively that the emerging outbreak of atypical pneumonia cases is consistent with causation by a novel pathogen. The proposed approach, which uses only routinely observed non-virological data, can aid ongoing risk assessments in advance of virological test results becoming available.",2020,"Jung, Sung-Mok; Kinoshita, Ryo; Thompson, Robin N.; Linton, Natalie M.; Yang, Yichi; Akhmetzhanov, Andrei R.; Nishiura, Hiroshi",J Clin Med,3003574291,#3387,True
247161ad51b7f362e9cadfcd39e94dd6a1a26ca3,CZI,"A conceptual model for the outbreak of Coronavirus disease 2019 (COVID-19) in Wuhan, China with individual reaction and governmental action",10.1016/j.ijid.2020.02.058,,,cc-by-nc-nd,"The ongoing Coronavirus Disease 2019 (COVID-19) outbreak, originated in the end of 2019 in Wuhan, China, has claimed more than 2200 lives and posed a huge threat to global public health. The Chinese government has implemented control measures including setting up special hospitals and travel restriction to mitigate the spread. We propose conceptual models for the outbreak in Wuhan with the consideration of individual behavioural reaction and governmental actions, e.g., holiday extension, travel restriction, hospitalisation and quarantine. We employed the estimates of these two key components from the 1918 influenza pandemic in London, United Kingdom, incorporated zoonotic introductions and the emigration, then computed future trends and the reporting ratio. The model is concise in structure, and it successfully captures the course of the COVID-19 outbreak, and thus sheds light on understanding the trends of the outbreak.",2020,"Lin, Qianying; Zhao, Shi; Gao, Daozhou; Lou, Yijun; Yang, Shu; Musa, Salihu S.; Wang, Maggie H.; Cai, Yongli; Wang, Weiming; Yang, Lin; He, Daihai",International Journal of Infectious Diseases,2604381070,#4507,True
4ecbacf61daab591e76f7471eb6e7fc1a4e0ed70,CZI,Potential role of inanimate surfaces for the spread of coronaviruses and their inactivation with disinfectant agents,10.1016/j.infpip.2020.100044,,,cc-by-nc-nd,"Summary The novel human coronavirus 2019-nCoV has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described, probably via droplets but possibly also via contaminated hands or surfaces. In a recent review on the persistence of human and veterinary coronaviruses on inanimate surfaces it was shown that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days. Some disinfectant agents effectively reduce coronavirus infectivity within 1 minute such 62% - 71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite. Other compounds such as 0.05% - 0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. An effective surface disinfection may help to ensure an early containment and prevention of further viral spread.",2020,"Kampf, Günter",Infection Prevention in Practice,3006062275,#867,True
804a9591280b7f64fa79cd3e4a9358976b084ffb,CZI,Revisiting the dangers of the coronavirus in the ophthalmology practice,10.1038/s41433-020-0790-7,,,cc-by,"A possible threat in the ophthalmology clinic While the 2019-nCoV transmission route is still unknown, countries have been preparing measures based on past experiences with coronaviruses namely SARS-CoV and MERS-CoV. These viruses transmit primarily through droplets and other bodily secretions. In the ophthalmology practice, healthcare workers may be particularly susceptible to these infections. Firstly, ophthalmologists are extremely reliant on physical examination during patient consultation. Of particular concern is the proximity between the patient and ophthalmologist during the slit lamp microscope examination. It has been shown that droplets from a cough or sneeze can be propelled for up to 6?m [8], a range that definitely encompasses the distance between the patient and ophthalmologist. Secondly, during the SARS-CoV epidemic, clinical reports have suggested tears as a medium of infection. In a case series by Loon et al., it was shown that viral RNA of the SARS-CoV can be detected by reverse-transcription polymerase chain reaction (RT-PCR) from the tears of infected individuals [9]. While anecdotal in nature, such accounts highlight the possible infectivity of tears, a fluid which ophthalmologists and instruments come in contact on a daily basis. If true, this represents a crucial need for further development of disinfection and personal protective equipment (PPE) protocols for the ophthalmology clinic.SN - 1476-5454",2020,"Seah, Ivan; Su, Xinyi; Lingam, Gopal",Eye,3005477973,#375,True
12d267205009c178b6a50506db717ff650d93415,CZI,A pneumonia outbreak associated with a new coronavirus of probable bat origin,10.1038/s41586-020-2012-7,,32015507,cc-by,"Since the SARS outbreak 18 years ago, a large number of severe acute respiratory syndrome-related coronaviruses (SARSr-CoV) have been discovered in their natural reservoir host, bats(1-4). Previous studies indicated that some of those bat SARSr-CoVs have the potential to infect humans(5-7). Here we report the identification and characterization of a novel coronavirus (2019-nCoV) which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started from 12 December 2019, has caused 2,050 laboratory-confirmed infections with 56 fatal cases by 26 January 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV. The 2019-nCoV virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, we have confirmed that this novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.",2020,"Zhou, Peng; Yang, Xing-Lou; Wang, Xian-Guang; Hu, Ben; Zhang, Lei; Zhang, Wei; Si, Hao-Rui; Zhu, Yan; Li, Bei; Huang, Chao-Lin; Chen, Hui-Dong; Chen, Jing; Luo, Yun; Guo, Hua; Jiang, Ren-Di; Liu, Mei-Qin; Chen, Ying; Shen, Xu-Rui; Wang, Xi; Zheng, Xiao-Shuang; Zhao, Kai; Chen, Quan-Jiao; Deng, Fei; Liu, Lin-Lin; Yan, Bing; Zhan, Fa-Xian; Wang, Yan-Yi; Xiao, Geng-Fu; Shi, Zheng-Li",Nature,3004280078,#246,True
f3fa89e819a64d2d6c74f6d590661ca435878c26,CZI,Overview of The 2019 Novel Coronavirus (2019-nCoV): The Pathogen of Severe Specific Contagious Pneumonia (SSCP),10.1097/JCMA.0000000000000270,,32049687,cc-by-nc-nd,"In late December 2019 a previous unidentified coronavirus, currently named as the 2019 novel coronavirus (2019-nCoV), emerged from Wuhan, China and resulted in a formidable outbreak in many cities in China and expanding globally, including Thailand, Republic of Korea, Japan, USA, Philippines, Viet Nam, and our country (as of 2/6/2020 at least 25 countries). The disease is officially named as the Severe Specific Contagious Pneumonia (SSCP) in 1/15/2019 and is a notifiable communicable disease of the 5 category by the Taiwan CDC, the Ministry of Health. SSCP is a potential zoonotic disease with low to moderate (estimated 2-5%) mortality rate. Person-to-person transmission may occur through droplet or contact transmission and jeopardized first-line healthcare workers if lack of stringent infection control or no proper personal protective equipment available. Currently, there is no definite treatment for SSCP although some drugs are under investigation. To promptly identify patients and prevent further spreading, physicians should be aware of travel or contact history for patients with compatible symptoms.",2020,"Wu, Yi-Chi; Chen, Ching-Sung; Chan, Yu-Jiun",J Chin Med Assoc,3006472059,#717,True
018269476cd191365d6b8bed046078aea07c8c01,CZI,A mathematical model for simulating the phase-based transmissibility of a novel coronavirus,10.1186/s40249-020-00640-3,,,cc-by,"Background As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. The virus was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by International Committee on Taxonomy of Viruses on 11 February, 2020. This study aimed to develop a mathematical model for calculating the transmissibility of the virus. Methods In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probably be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market (reservoir) to people, we simplified the model as Reservoir-People (RP) transmission network model. The next generation matrix approach was adopted to calculate the basic reproduction number (R 0) from the RP model to assess the transmissibility of the SARS-CoV-2. Results The value of R 0 was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58. Conclusions Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries, similar to severe acute respiratory syndrome, but lower than MERS in the Republic of Korea.",2020,"Yin, Tian-Mu Chen; Jia, Rui; Qiu-Peng, Wang; Ze-Yu, Zhao; Jing-An, Cui; Ling",Infectious Diseases of Poverty,2998953329,#2762,True
489040d34aa5dc8e6eba3d4e9d3d48f0bcc6061f,CZI,"Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China [version 2; peer review: 2 approved]",10.12688/f1000research.22211.2,,,cc-by,"A novel coronavirus (2019-nCoV) originating in Wuhan, China presents a potential respiratory viral pandemic to the world population. Current efforts are focused on containment and quarantine of infected individuals. Ultimately, the outbreak could be controlled with a protective vaccine to prevent 2019-nCoV infection. While vaccine research should be pursued intensely, there exists today no therapy to treat 2019-nCoV upon infection, despite an urgent need to find options to help these patients and preclude potential death. Herein, I review the potential options to treat 2019-nCoV in patients, with an emphasis on the necessity for speed and timeliness in developing new and effective therapies in this outbreak. I consider the options of drug repurposing, developing neutralizing monoclonal antibody therapy, and an oligonucleotide strategy targeting the viral RNA genome, emphasizing the promise and pitfalls of these approaches. Finally, I advocate for the fastest strategy to develop a treatment now, which could be resistant to any mutations the virus may have in the future. The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain (ACE2-Fc), providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. The ACE2-Fc therapy would also supplement decreased ACE2 levels in the lungs during infection, thereby directly treating acute respiratory distress pathophysiology as a third mechanism of action. The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drug today to treat patients under compassionate use, while formal clinical trials are later undertaken. Such a treatment could help infected patients before a protective vaccine is developed and widely available in the coming months to year(s).",2020,"Kruse, Robert L.",F1000Research,3004071935,#1971,True
97040e1e32165ddc6f5ac806f9d970c4141c561e,CZI,2019-novel Coronavirus (2019-nCoV): estimating the case fatality rate - a word of caution,10.4414/smw.2020.20203,,32031234,cc-by-nc-nd,,2020,"Battegay, Manuel; Kuehl, Richard; Tschudin-Sutter, Sarah; Hirsch, Hans H.; Widmer, Andreas F.; Neher, Richard A.",Swiss Med Wkly,3005409672,#491,True
09c84b9de7fc5c3fed4736e7a3cd45e112377042,CZI,COVID-19 in the Shadows of MERS-CoV in the Kingdom of Saudi Arabia,10.2991/jegh.k.200218.003,,,cc-by-nc,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has plagued the Middle East since it was first reported in 2012. Recently, at the end of December 2019, a cluster of pneumonia cases were reported from Wuhan city, Hubei Province, China, linked to a wet seafood market with a new coronavirus identified as the etiologic agent currently named SARS-CoV-2. Most cases are in Mainland China with international spread to 25 countries. The novelty of the virus, the rapid national and international spread, and the lack of therapeutic and preventative strategies have led the WHO International Health Regulation emergency committee to declare the disease as Public Health Emergency of International Concern (PHEIC) on January 30, 2020. As it relates to countries with the ongoing MERS-CoV community cases and hospital acquired infections, there will be a huge challenge for HCWs to deal with both coronaviruses, especially with the lack of standardized and approved point of care testing. This challenge will now be faced by the whole global health community dealing with COVID-19 since both coronaviruses have similar presentation. Those patients should now be tested for both MERS-CoV and SARS-CoV-2 simultaneously, and with the continuing wide international spread of SARS-CoV-2, the travel history to China in the last 14 days will be of less significance",2020,"Memish, Mazin Barry; Maha Al, Amri; Ziad, A.",Journal of Epidemiology and Global Health,2093640054,#2899,True
7af7848a33dc0c6599e902e9c155ab68fa72ffad,CZI,Communicating the Risk of Death from Novel Coronavirus Disease (COVID-19),10.3390/jcm9020580,,,cc-by,"To understand the severity of infection for a given disease, it is common epidemiological practice to estimate the case fatality risk, defined as the risk of death among cases. However, there are three technical obstacles that should be addressed to appropriately measure this risk. First, division of the cumulative number of deaths by that of cases tends to underestimate the actual risk because deaths that will occur have not yet observed, and so the delay in time from illness onset to death must be addressed. Second, the observed dataset of reported cases represents only a proportion of all infected individuals and there can be a substantial number of asymptomatic and mildly infected individuals who are never diagnosed. Third, ascertainment bias and risk of death among all those infected would be smaller when estimated using shorter virus detection windows and less sensitive diagnostic laboratory tests. In the ongoing COVID-19 epidemic, health authorities must cope with the uncertainty in the risk of death from COVID-19, and high-risk individuals should be identified using approaches that can address the abovementioned three problems. Although COVID-19 involves mostly mild infections among the majority of the general population, the risk of death among young adults is higher than that of seasonal influenza, and elderly with underlying comorbidities require additional care.",2020,"Kobayashi, Tetsuro; Jung, Sung-mok; Linton, M. Natalie; Kinoshita, Ryo; Hayashi, Katsuma; Miyama, Takeshi; Anzai, Asami; Yang, Yichi; Yuan, Baoyin; Akhmetzhanov, R. Andrei; Suzuki, Ayako; Nishiura, Hiroshi",Journal of Clinical Medicine,3005847234,#1603,True
7e8409337e69a72191475029805c6776ad43b60b,CZI,"2019-nCoV (Wuhan virus), a novel Coronavirus: Human-to-human transmission, travel-related cases, and vaccine readiness",10.3855/jidc.12425,,,cc-by,"On 31 December 2019 the Wuhan Health Commission reported a cluster of atypical pneumonia cases that was linked to a wet market in the city of Wuhan, China. The first patients began experiencing symptoms of illness in mid-December 2019. Clinical isolates were found to contain a novel coronavirus with similarity to bat coronaviruses. As of 28 January 2020, there are in excess of 4,500 laboratory-confirmed cases, with > 100 known deaths. As with the SARS-CoV, infections in children appear to be rare. Travel-related cases have been confirmed in multiple countries and regions outside mainland China including Germany, France, Thailand, Japan, South Korea, Vietnam, Canada, and the United States, as well as Hong Kong and Taiwan. Domestically in China, the virus has also been noted in several cities and provinces with cases in all but one provinence. While zoonotic transmission appears to be the original source of infections, the most alarming development is that human-to-human transmission is now prevelant. Of particular concern is that many healthcare workers have been infected in the current epidemic. There are several critical clinical questions that need to be resolved, including how efficient is human-to-human transmission? What is the animal reservoir? Is there an intermediate animal reservoir? Do the vaccines generated to the SARS-CoV or MERS-CoV or their proteins offer protection against 2019-nCoV? We offer a research perspective on the next steps for the generation of vaccines. We also present data on the use of in silico docking in gaining insight into 2019-nCoV Spike-receptor binding to aid in therapeutic development. Diagnostic PCR protocols can be found at https://www.who.int/health-topics/coronavirus/laboratory-diagnostics-for-novel-coronavirus.",2020,"Ralph, R.; Lew, J.; Zeng, T.; Francis, M.; Xue, B.; Roux, M.; Ostadgavahi, A. T.; Rubino, S.; Dawe, N. J.; Al-Ahdal, M. N.; Kelvin, D. J.; Richardson, C. D.; Kindrachuk, J.; Falzarano, D.; Kelvin, A. A.",Journal of Infection in Developing Countries,3004705239,#1512,True
24a525b0319b028b8898f731d49b84f467ae2c73,CZI,A potential role for integrins in host cell entry by SARS-CoV-2,10.1016/j.antiviral.2020.104759,,,cc-by,,2020,"Sigrist, Christian; Bridge, Alan; Le Mercier, Philippe",Antiviral Research,2163643581,#2945,True
2271485cae8757f2abdb1c2d012bb892c5421ba4,CZI,A strategy to prevent future pandemics similar to the 2019-nCoV outbreak,10.1016/j.bsheal.2020.01.003,,,cc-by-nc-nd,"A novel bat-origin coronavirus emerged in Wuhan, China in December 2019 and continues to spread across China and the world. At the time of writing, a massive global response has been implemented to control the disease as it spreads from person to person. Yet the high-risk human-wildlife interactions and interfaces that led to the emergence of SARS-CoV and of 2019-nCoV continue to exist in emerging disease hotspots globally. To prevent the next pandemic related to these interfaces, we call for research and investment in three areas: 1) surveillance among wildlife to identify the high-risk pathogens they carry; 2) surveillance among people who have contact with wildlife to identify early spillover events; and 3) improvement of market biosecurity regarding the wildlife trade. As the emergence of a novel virus anywhere can impact the furthest reaches of our connected world, international collaboration among scientists is essential to address these risks and prevent the next pandemic.",2020,"Daszak, Peter; Olival, Kevin J.; Li, Hongying",Biosafety and Health,3004767366,#416,True
19ff77e874c0706f794908e9b6878314671d385a,CZI,A distinct name is needed for the new coronavirus,10.1016/S0140-6736(20)30419-0,,,pd,,2020,"Jiang, Shibo; Shi, Zhengli; Shu, Yuelong; Song, Jingdong; Gao, George F.; Tan, Wenjie; Guo, Deyin",The Lancet,3003788575,#1297,True
22694a0a131da58c1a82a0d2d1556e0ccd8617c5,CZI,"The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health — The latest 2019 novel coronavirus outbreak in Wuhan, China - International Journal of Infectious Diseases",10.1016/j.ijid.2020.01.009,,,cc-by-nc-nd,"The city of Wuhan in China is the focus of global attention due to an outbreak of a febrile respiratory illness due to a coronavirus 2019-nCoV. In December 2019, there was an outbreak of pneumonia of unknown cause in Wuhan, Hubei province in China, with an epidemiological link to the Huanan Seafood Wholesale Market where there was also sale of live animals. Notification of the WHO on 31 Dec 2019 by the Chinese Health Authorities has prompted health authorities in Hong Kong, Macau, and Taiwan to step up border surveillance, and generated concern and fears that it could mark the emergence of a novel and serious threat to public health (WHO, 2020a; Parr, 2020).",2020,"Hui, David S.",International Journal of Infectious Diseases,,#2254,True
637939a0f462b9e821ff62fc20e9fedfe78df73e,CZI,"Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: A data-driven analysis in the early phase of the outbreak",10.1016/j.ijid.2020.01.050,,,cc-by-nc-nd,"Backgrounds An ongoing outbreak of a novel coronavirus (2019-nCoV) pneumonia hit a major city of China, Wuhan, December 2019 and subsequently reached other provinces/regions of China and countries. We present estimates of the basic reproduction number,R0, of 2019-nCoV in the early phase of the outbreak. Methods Accounting for the impact of the variations in disease reporting rate, we modelled the epidemic curve of 2019-nCoV cases time series, in mainland China from January 10 to January 24, 2020, through the exponential growth. With the estimated intrinsic growth rate (γ), we estimated R0 by using the serial intervals (SI) of two other well-known coronavirus diseases, MERS and SARS, as approximations for the true unknown SI. Findings The early outbreak data largely follows the exponential growth. We estimated that the meanR0 ranges from 2.24 (95%CI: 1.96-2.55) to 3.58 (95%CI: 2.89-4.39) associated with 8-fold to 2-fold increase in the reporting rate. We demonstrated that changes in reporting rate substantially affect estimates of R0. Conclusion The mean estimate ofR0 for the 2019-nCoV ranges from 2.24 to 3.58, and significantly larger than 1. Our findings indicate the potential of 2019-nCoV to cause outbreaks.",2020,"Zhao, Shi; Lin, Qianyin; Ran, Jinjun; Musa, Salihu S.; Yang, Guangpu; Wang, Weiming; Lou, Yijun; Gao, Daozhou; Yang, Lin; He, Daihai; Wang, Maggie H.",International Journal of Infectious Diseases,3004397688,#100,True
9756bb3c608ed790d2306fc8db815a694eeca45f,CZI,Transmission routes of 2019-nCoV and controls in dental practice,10.1038/s41368-020-0075-9,,,cc-by,"A novel β-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal–oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.",2020,"Peng, Xian; Xu, Xin; Li, Yuqing; Cheng, Lei; Zhou, Xuedong; Ren, Biao",International Journal of Oral Science,659484933,#3135,True
a67012609fad77c2a1dc55f139b044c546cd13a8,CZI,Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study,10.1097/cm9.0000000000000722,,32004165,cc-by-nc-nd,"BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital of Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown beta-CoV strain in all five patients, with 99.8-99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6-87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.",2020,"Ren, L. L.; Wang, Y. M.; Wu, Z. Q.; Xiang, Z. C.; Guo, L.; Xu, T.; Jiang, Y. Z.; Xiong, Y.; Li, Y. J.; Li, H.; Fan, G. H.; Gu, X. Y.; Xiao, Y.; Gao, H.; Xu, J. Y.; Yang, F.; Wang, X. M.; Wu, C.; Chen, L.; Liu, Y. W.; Liu, B.; Yang, J.; Wang, X. R.; Dong, J.; Li, L.; Huang, C. L.; Zhao, J. P.; Hu, Y.; Cheng, Z. S.; Liu, L. L.; Qian, Z. H.; Qin, C.; Jin, Q.; Cao, B.; Wang, J. W.",Chinese medical journal,3003639008,#122,True
ce5f0965088e41390e671d3d16d65ccd777efa21,CZI,Proposal for prevention and control of the 2019 novel coronavirus disease in newborn infants,10.1136/archdischild-2020-318996,,32132140,cc-by-nc,,2020,"Li, F.; Feng, Z. C.; Shi, Y.",Archives of disease in childhood. Fetal and neonatal edition,3004790666,#4804,True
a0682c2b9aabc40d6daca4496ceec2ccd0583aab,CZI,Epitope-based peptide vaccine design and target site depiction against Middle East Respiratory Syndrome Coronavirus: An immune-informatics study,10.1186/s12967-019-2116-8,,,cc-by,"Background: Middle East Respiratory Syndrome Coronavirus (MERS-COV) is the main cause of lung and kidney infections in developing countries such as Saudi Arabia and South Korea. This infectious single-stranded, positive (+) sense RNA virus enters the host by binding to dipeptidyl-peptide receptors. Since no vaccine is yet available for MERS-COV, rapid case identification, isolation, and infection prevention strategies must be used to combat the spreading of MERS-COV infection. Additionally, there is a desperate need for vaccines and antiviral strategies. Methods: The present study used immuno-informatics and computational approaches to identify conserved B-and T cell epitopes for the MERS-COV spike (S) protein that may perform a significant role in eliciting the resistance response to MERS-COV infection. Results: Many conserved cytotoxic T-lymphocyte epitopes and discontinuous and linear B-cell epitopes were predicted for the MERS-COV S protein, and their antigenicity and interactions with the human leukocyte antigen (HLA) B7 allele were estimated. Among B-cell epitopes, QLQMGFGITVQYGT displayed the highest antigenicity-score, and was immensely immunogenic. Among T-cell epitopes, MHC class-I peptide YKLQPLTFL and MHC class-II peptide YCILEPRSG were identified as highly antigenic. Furthermore, docking analyses revealed that the predicted peptides engaged in strong bonding with the HLA-B7 allele. Conclusion: The present study identified several MERS-COV S protein epitopes that are conserved among various isolates from different countries. The putative antigenic epitopes may prove effective as novel vaccines for eradication and combating of MERS-COV infection.",2019,"Tahir Ul Qamar, M.; Saleem, S.; Ashfaq, U. A.; Bari, A.; Anwar, F.; Alqahtani, S.",Journal of Translational Medicine,2987491742,#21,True
0eb44c0cc59184754a0a2cd8ee3c8b2302a8927c,CZI,Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR,10.2807/1560-7917.ES.2020.25.3.2000045,,,cc-by,"BackgroundThe ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur.AimWe aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available.MethodsHere we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology.ResultsThe workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive - Global (EVAg), a European Union infrastructure project.ConclusionThe present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.",2020,"Corman, V. M.; Landt, O.; Kaiser, M.; Molenkamp, R.; Meijer, A.; Chu, D. K.; Bleicker, T.; Brünink, S.; Schneider, J.; Schmidt, M. L.; Mulders, D. G.; Haagmans, B. L.; van der Veer, B.; van den Brink, S.; Wijsman, L.; Goderski, G.; Romette, J. L.; Ellis, J.; Zambon, M.; Peiris, M.; Goossens, H.; Reusken, C.; Koopmans, M. P.; Drosten, C.",Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,3001195213,#233,True
90d04764b497a224a1d969f4e317fc19a5feab35,CZI,On the Coronavirus (COVID-19) Outbreak and the Smart City Network: Universal Data Sharing Standards Coupled with Artificial Intelligence (AI) to Benefit Urban Health Monitoring and Management,10.3390/healthcare8010046,,,cc-by,"As the Coronavirus (COVID-19) expands its impact from China, expanding its catchment into surrounding regions and other countries, increased national and international measures are being taken to contain the outbreak. The placing of entire cities in ‘lockdown’ directly affects urban economies on a multi-lateral level, including from social and economic standpoints. This is being emphasised as the outbreak gains ground in other countries, leading towards a global health emergency, and as global collaboration is sought in numerous quarters. However, while effective protocols in regard to the sharing of health data is emphasised, urban data, on the other hand, specifically relating to urban health and safe city concepts, is still viewed from a nationalist perspective as solely benefiting a nation’s economy and its economic and political influence. This perspective paper, written one month after detection and during the outbreak, surveys the virus outbreak from an urban standpoint and advances how smart city networks should work towards enhancing standardization protocols for increased data sharing in the event of outbreaks or disasters, leading to better global understanding and management of the same.",2020,"Allam, Zaheer; Jones, David S.",Healthcare,2558035409,#3221,True
bf20dda99538a594eafc258553634fd9195104cb,CZI,Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak,10.3390/jcm9020388,,,cc-by,"Background: In December 2019, an outbreak of respiratory illness caused by a novel coronavirus (2019-nCoV) emerged in Wuhan, China and has swiftly spread to other parts of China and a number of foreign countries. The 2019-nCoV cases might have been under-reported roughly from 1 to 15 January 2020, and thus we estimated the number of unreported cases and the basic reproduction number, R0, of 2019-nCoV. Methods: We modelled the epidemic curve of 2019-nCoV cases, in mainland China from 1 December 2019 to 24 January 2020 through the exponential growth. The number of unreported cases was determined by the maximum likelihood estimation. We used the serial intervals (SI) of infection caused by two other well-known coronaviruses (CoV), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) CoVs, as approximations of the unknown SI for 2019-nCoV to estimate R0. Results: We confirmed that the initial growth phase followed an exponential growth pattern. The under-reporting was likely to have resulted in 469 (95% CI: 403−540) unreported cases from 1 to 15 January 2020. The reporting rate after 17 January 2020 was likely to have increased 21-fold (95% CI: 18−25) in comparison to the situation from 1 to 17 January 2020 on average. We estimated the R0 of 2019-nCoV at 2.56 (95% CI: 2.49−2.63). Conclusion: The under-reporting was likely to have occurred during the first half of January 2020 and should be considered in future investigation.",2020,"Zhao, Shi; Musa, Salihu S.; Lin, Qianying; Ran, Jinjun; Yang, Guangpu; Wang, Weiming; Lou, Yijun; Yang, Lin; Gao, Daozhou; He, Daihai; Wang, Maggie H.",Journal of Clinical Medicine,3004200727,#131,True
16d4d6332fb5f17df0c487e2c9202716d01889be,CZI,SARS-CoV-2 infection in children: Transmission dynamics and clinical characteristics,10.1016/j.jfma.2020.02.009,,,cc-by-nc-nd,,2020,"Cao, Qing; Chen, Yi-Ching; Chen, Chyi-Liang; Chiu, Cheng-Hsun",Journal of the Formosan Medical Association,3005688502,#3205,True
3e5edc4ff36064478e209800a15365cd5f710756,CZI,First case of Coronavirus Disease 2019 (COVID-19) pneumonia in Taiwan,10.1016/j.jfma.2020.02.007,,,cc-by-nc-nd,"An outbreak of respiratory illness proved to be infected by a 2019 novel coronavirus, officially named Coronavirus Disease 2019 (COVID-19), was notified first in Wuhan, China, and has spread rapidly in China and to other parts of the world. Herein, we reported the first confirmed case of novel coronavirus pneumonia (NCP) imported from China in Taiwan. This case report revealed a natural course of NCP with self-recovery, which may be a good example in comparison with medical treatments.",2020,"Cheng, Shao-Chung; Chang, Yuan-Chia; Fan Chiang, Yu-Long; Chien, Yu-Chan; Cheng, Mingte; Yang, Chin-Hua; Huang, Chia-Husn; Hsu, Yuan-Nian",Journal of the Formosan Medical Association,3005657121,#2326,True
58b5c77c9fb3f68a3ad84a3f15275dc0e4554192,CZI,From SARS to COVID-19: A previously unknown SARS-CoV-2 virus of pandemic potential infecting humans – Call for a One Health approach,10.1016/j.onehlt.2020.100124,,,cc-by-nc-nd,"Human coronaviruses continue to pose a threat to human health. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 which causes coronavirus disease-2019 (COVID-19), an acute respiratory disease marked the third introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. This recent ongoing emergence of a previously unknown coronavirus in China leads to huge impacts on humans globally. Here, we discuss the outbreak in a one health context, highlighting the need for the implementation of one health measures and practices to improve human health and reduce the emergence of pandemic viruses.",2020,"El Zowalaty, Mohamed E.; Järhult, Josef D.",One Health,,#1850,True
0f5842185d3392825e5ab3768ecb832fb25a3b25,CZI,Real-Time Estimation of the Risk of Death from Novel Coronavirus (COVID-19) Infection: Inference Using Exported Cases,10.3390/jcm9020523,,,cc-by,"The exported cases of 2019 novel coronavirus (COVID-19) infection that were confirmed outside China provide an opportunity to estimate the cumulative incidence and confirmed case fatality risk (cCFR) in mainland China. Knowledge of the cCFR is critical to characterize the severity and understand the pandemic potential of COVID-19 in the early stage of the epidemic. Using the exponential growth rate of the incidence, the present study statistically estimated the cCFR and the basic reproduction number—the average number of secondary cases generated by a single primary case in a naïve population. We modeled epidemic growth either from a single index case with illness onset on 8 December, 2019 (Scenario 1), or using the growth rate fitted along with the other parameters (Scenario 2) based on data from 20 exported cases reported by 24 January 2020. The cumulative incidence in China by 24 January was estimated at 6924 cases (95% confidence interval [CI]: 4885, 9211) and 19,289 cases (95% CI: 10,901, 30,158), respectively. The latest estimated values of the cCFR were 5.3% (95% CI: 3.5%, 7.5%) for Scenario 1 and 8.4% (95% CI: 5.3%, 12.3%) for Scenario 2. The basic reproduction number was estimated to be 2.1 (95% CI: 2.0, 2.2) and 3.2 (95% CI: 2.7, 3.7) for Scenarios 1 and 2, respectively. Based on these results, we argued that the current COVID-19 epidemic has a substantial potential for causing a pandemic. The proposed approach provides insights in early risk assessment using publicly available data.",2020,"Jung, Sung-mok; Akhmetzhanov, Andrei R.; Hayashi, Katsuma; Linton, Natalie M.; Yang, Yichi; Yuan, Baoyin; Kobayashi, Tetsuro; Kinoshita, Ryo; Nishiura, Hiroshi",Journal of Clinical Medicine,3005847234,#965,True
9b0c87f808b1b66f2937d7a7acb524a756b6113b,CZI,"Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review",10.3390/jcm9030623,,,cc-by,"Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.",2020,"Pang, Junxiong; Wang, Min Xian; Ang, Ian Yi Han; Tan, Sharon Hui Xuan; Lewis, Ruth Frances; Chen, Jacinta I. Pei; Gutierrez, Ramona A.; Gwee, Sylvia Xiao Wei; Chua, Pearleen Ee Yong; Yang, Qian; Ng, Xian Yi; Yap, Rowena K. S.; Tan, Hao Yi; Teo, Yik Ying; Tan, Chorh Chuan; Cook, Alex R.; Yap, Jason Chin-Huat; Hsu, Li Yang",Journal of Clinical Medicine,3001515529,#2155,True
cff7fb355c096e08503caf3108f7b01525318634,CZI,Comparison of different samples for 2019 novel coronavirus detection by nucleic acid amplification tests,10.1016/j.ijid.2020.02.050,,,cc-by-nc-nd,"A severe respiratory ongoing outbreak of pneumonia associated with 2019 novel coronavirus was recently emerged in China. Here, we reported the epidemiological, clinical, laboratory and radiological characteristics of 19 suspect cases. We compared the positive ratio of 2019-nCoV nucleic acid amplification test from different samples including oropharyngeal swab, blood, urine and stool with 3different Fluorescent RT-PCR kits. Nine out of the 19 patients were detected 2019-nCoV infection using oropharyngeal swab samples, and the virus nucleic acid was also detected in eight of these nine patients using stool samples. None of positive results was identified in the blood and urine samples. Thses three different kits got the same result for each sample and the positive ratio of nucleic acid detection for 2019-nCoV was only 47.4% in the suspect patients. Therefore, it is possible that the really infected patients have been missed by using nucleic acid detection only. It might be better to make a diagnosis combining the Computed Tomography scans and the nucleic acid detection together.",2020,"Xie, Chunbao; Jiang, Lingxi; Huang, Guo; Pu, Hong; Gong, Bo; Lin, He; Ma, Shi; Chen, Xuemei; Long, Bo; Si, Guo; Yu, Hua; Jiang, Li; Yang, Xingxiang; Shi, Yi; Yang, Zhenglin",International Journal of Infectious Diseases,2081372128,#2506,True
4790e3eb0374a7f159014ef77ec42a6b9de91c29,CZI,Personal knowledge on novel coronavirus pneumonia,10.1097/CM9.0000000000000757,,32068600,cc-by-nc-nd,,2020,"Kang, Han-Yujie; Wang, Yi-Shan; Tong, Zhao-Hui",Chin Med J (Engl),3002108456,#1226,True
e4d53d6c63d62095343315894b1f882efe299f7d,CZI,"Differential diagnosis of illness in patients under investigation for the novel coronavirus (SARS-CoV-2), Italy, February 2020",10.2807/1560-7917.ES.2020.25.8.2000170,,,cc-by,,2020,"Bordi, Licia; Nicastri, Emanuele; Scorzolini, Laura; Caro, Antonino Di; Capobianchi, Maria Rosaria; Castilletti, Concetta; Lalle, Eleonora; group, on behalf of INMI COVID-19 study; Centers2, Collaborating",Eurosurveillance,2046423558,#2677,True
1c7db6e51155dadaaffd563ef1e560011b25ae92,CZI,"Novel Coronavirus Outbreak in Wuhan, China, 2020: Intense Surveillance Is Vital for Preventing Sustained Transmission in New Locations",10.3390/jcm9020498,,32054124,cc-by,"The outbreak of pneumonia originating in Wuhan, China, has generated 24,500 confirmed cases, including 492 deaths, as of 5 February 2020. The virus (2019-nCoV) has spread elsewhere in China and to 24 countries, including South Korea, Thailand, Japan and USA. Fortunately, there has only been limited human-to-human transmission outside of China. Here, we assess the risk of sustained transmission whenever the coronavirus arrives in other countries. Data describing the times from symptom onset to hospitalisation for 47 patients infected early in the current outbreak are used to generate an estimate for the probability that an imported case is followed by sustained human-to-human transmission. Under the assumptions that the imported case is representative of the patients in China, and that the 2019-nCoV is similarly transmissible to the SARS coronavirus, the probability that an imported case is followed by sustained human-to-human transmission is 0.41 (credible interval [0.27, 0.55]). However, if the mean time from symptom onset to hospitalisation can be halved by intense surveillance, then the probability that an imported case leads to sustained transmission is only 0.012 (credible interval [0, 0.099]). This emphasises the importance of current surveillance efforts in countries around the world, to ensure that the ongoing outbreak will not become a global pandemic.",2020,"Thompson, Robin N.",J Clin Med,3006121899,#910,True
ffee1423c1320d7070fe9a871224a468768a4c10,CZI,"Authoritarianism, outbreaks, and information politics",10.1016/S2468-2667(20)30030-X,,,cc-by,,2020,"Kavanagh, Matthew M.",The Lancet Public Health,3006271029,#834,True
353852971069ad5794445e5c1ab6077ce23da75d,CZI,Crowdsourcing data to mitigate epidemics,10.1016/S2589-7500(20)30055-8,,,cc-by-nc-nd,,2020,"Leung, Gabriel M.; Leung, Kathy",The Lancet Digital Health,2154231974,#1386,True
fa46fb0587956a218b9b81d5aa6b2a6c7ec68126,CZI,"Should, and how can, exercise be done during a coronavirus outbreak? — An interview with Dr. Jeffrey A. Woods",10.1016/j.jshs.2020.01.005,,,cc-by-nc-nd,,2020,"Zhu, Weimo",Journal of Sport and Health Science,,#206,True
4a8852f2970eadd44d677311548ca6eea1c5079f,CZI,The novel Coronavirus (SARS-CoV-2) is a one health issue,10.1016/j.onehlt.2020.100123,,,cc-by-nc-nd,,2020,"Marty, Aileen Maria; Jones, Malcolm K.",One Health,3005802710,#2589,True
02652961663ca435c195fb0ed3e43642e04cfab3,CZI,Authors’ response: Plenty of coronaviruses but no SARS-CoV-2,10.2807/1560-7917.ES.2020.25.8.2000197,,,cc-by,,2020,"Reusken, Chantal B; Haagmans, Bart; Meijer, Adam; Corman, Victor M; Papa, Anna; Charrel, Remi; Drosten, Christian; Koopmans, Marion",Eurosurveillance,,#2561,True
913cd784df40966fdfd97281dd38d9c9b421f32e,CZI,2019 Novel Coronavirus (COVID-19) Pneumonia: Serial Computer Tomography Findings,10.3348/kjr.2020.0112,,32100486,cc-by-nc,"From December 2019, Coronavirus disease 2019 (COVID-19) pneumonia (formerly known as the 2019 novel Coronavirus [2019-nCoV]) broke out in Wuhan, China. In this study, we present serial CT findings in a 40-year-old female patient with COVID-19 pneumonia who presented with the symptoms of fever, chest tightness, and fatigue. She was diagnosed with COVID-19 infection confirmed by real-time reverse-transcriptase-polymerase chain reaction. CT showed rapidly progressing peripheral consolidations and ground-glass opacities in both lungs. After treatment, the lesions were shown to be almost absorbed leaving the fibrous lesions.",2020,"Wei, J.; Xu, H.; Xiong, J.; Shen, Q.; Fan, B.; Ye, C.; Dong, W.; Hu, F.",Korean journal of radiology,3005148615,#4414,True
2ef7ce66fc8445aa7bfabc121193e2ae0091fecb,CZI,2019-nCoV: Polite with children!,10.4081/pr.2020.8495,,,cc-by-nc,"A novel epidemic is challenging the global health care system. Starting from probably November to December 2019, another Coronavirus entered the arena of human pathogens, to be then defined 2019- nCoV [...].",2020,"Aricò, Désirée Caselli; Maurizio",Pediatric Reports. 2020;12(1),3006451293,#700,True
421f8341eae777852e0b4584e7221b39a0544518,CZI,"The Politics of Disease Epidemics: a Comparative Analysis of the SARS, Zika, and Ebola Outbreaks",10.1007/s40609-018-0123-y,,,cc-by,"Over the past few decades, disease outbreaks have become increasingly frequent and widespread. The epicenters of these outbreaks have differed, and could be linked to different economic contexts. Arguably, the responses to these outbreaks have been “political” and inherently burdensome to marginalized populations. Key lessons can be learned from exploring the narratives about the different epidemics in varying income settings. Based on a review of the published medical, social, and political literature, which was accessed using four electronic databases—PubMed, Sociological Abstracts, Scholars Portal, and Web of Science, the overall objective of this paper discuss scholars’ narratives on the “politics” of Ebola in a low-income setting, Zika virus in a middle-income setting, and SARS in a high-income setting. Various themes of the politics of epidemics were prominent in the literature. The narratives demonstrated the influence of power in whose narratives and what narratives are presented in the literature. While marginalized populations were reported to have borne the brunt of all disease outbreaks in the different contexts, the prevalence of their narratives within the reviewed literature was limited. Regardless of income setting, there is a need to give voice to the most marginalized communities during an epidemic. The experiences and narratives of those most vulnerable to an epidemic—specifically poor communities—need to be represented in the literature. This could contribute to mitigating some of the negative impact of the politics in epidemics.",2020,"Kapiriri, Lydia; Ross, Alison",Global Social Welfare,2890713974,#1136,True
ec53f9de631ca4386bc32b0947afc297418480f8,CZI,Emerging threats from zoonotic coronaviruses-from SARS and MERS to 2019-nCoV,10.1016/j.jmii.2020.02.001,,,cc-by-nc-nd,,2020,"Lee, Ping-Ing; Hsueh, Po-Ren","Journal of Microbiology, Immunology and Infection",3005473082,#224,True
1cf06efb631fff1394f207cd3ad09376ed85f8cb,CZI,"2019 novel coronavirus disease (COVID-19) in Taiwan: Reports of two cases from Wuhan, China",10.1016/j.jmii.2020.02.009,,,cc-by-nc-nd,"We reported two cases with community-acquired pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who returned from Wuhan, China in January, 2020. The reported cases highlight non-specific clinical presentations of 2019 novel coronavirus disease (COVID-19) as well as the importance of rapid laboratory-based diagnosis.",2020,"Huang, Wei-Hsuan; Teng, Ling-Chiao; Yeh, Ting-Kuang; Chen, Yu-Jen; Lo, Wei-Jung; Wu, Ming-Ju; Chin, Chun-Shih; Tsan, Yu-Tse; Lin, Tzu-Chieh; Chai, Jyh-Wen; Lin, Chin-Fu; Tseng, Chien-Hao; Liu, Chia-Wei; Wu, Chi-Mei; Chen, Po-Yen; Shi, Zhi-Yuan; Liu, Po-Yu","Journal of Microbiology, Immunology and Infection",3005943294,#1299,True
e827d65c421e5a5ed761cc56cc2a5f06a3545a82,CZI,Potential benefits of precise corticosteroids therapy for severe 2019-nCoV pneumonia,10.1038/s41392-020-0127-9,,,cc-by,"Salvage corticosteroids treatment for critical patients with 2019-nCoV? Corticosteroids are widely used to prevent lung injury caused by severe community-acquired pneumonia (sCAP) due to their excellent pharmacological effects on the suppression of exuberant and dysfunctional systematic inflammation5. Some scholars may not support the corticosteroids treatment for novel coronavirus pneumonia (NCP), because observational studies and systematic reviews have indicated inconclusive clinical evidence on the effect of corticosteroids therapy for viral pneumonias (such as SARS, MERS and H1N1). Additionally, pulse-dose therapy or long-term administration to high dose of corticosteroids in early stage were reported to be possibly harmful6,7,8. However, these conclusions obscured the clinical benefits of corticosteroids on some subgroups of patients, particularly those with severe symptoms, as the clinical effects might be related to the indication (severities of illness), the timing of intervention, the dose and duration of corticosteroids therapy9.",2020,"Gao, Wei Zhou; Yisi, Liu; Dongdong, Tian; Cheng, Wang; Sa, Wang; Jing, Cheng; Ming, Hu; Minghao, Fang; Yue",Signal Transduction and Targeted Therapy,2337846891,#1644,True
e9457327ddb51cf3ceb3698660ff08f526a09d44,CZI,Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease,10.1097/CM9.0000000000000775,,32118640,cc-by-nc-nd,"BACKGROUND: Since early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aims to investigate the factors affecting the progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia. METHODS: Patients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to 3 tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-squared test or Fisher exact test. Logistic regression analysis was performed to explore the risk factors for disease progression. RESULTS: Seventy-eight patients with COVID-19-induced pneumonia met the inclusion criteria and were included in this study. Efficacy evaluation at 2 weeks after hospitalization indicated that 11 patients (14.1%) had deteriorated, and 67 patients (85.9%) had improved/stabilized. The patients in the progression group were significantly older than those in the disease improvement/stabilization group (66 [51, 70] vs. 37 [32, 41] years, U = 4.932, P = 0.001). The progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilization group (27.3% vs. 3.0%, χ = 9.291, P = 0.018). For all the 78 patients, fever was the most common initial symptom, and the maximum body temperature at admission was significantly higher in the progression group than in the improvement/stabilization group (38.2 [37.8, 38.6] vs. 37.5 [37.0, 38.4]°C, U = 2.057, P = 0.027). Moreover, the proportion of patients with respiratory failure (54.5% vs. 20.9%, χ = 5.611, P = 0.028) and respiratory rate (34 [18, 48] vs. 24 [16, 60] breaths/min, U = 4.030, P = 0.004) were significantly higher in the progression group than in the improvement/stabilization group. C-reactive protein was significantly elevated in the progression group compared to the improvement/stabilization group (38.9 [14.3, 64.8] vs. 10.6 [1.9, 33.1] mg/L, U = 1.315, P = 0.024). Albumin was significantly lower in the progression group than in the improvement/stabilization group (36.62 ± 6.60 vs. 41.27 ± 4.55 g/L, U = 2.843, P = 0.006). Patients in the progression group were more likely to receive high-level respiratory support than in the improvement/stabilization group (χ = 16.01, P = 0.001). Multivariate logistic analysis indicated that age (odds ratio [OR], 8.546; 95% confidence interval [CI]: 1.628-44.864; P = 0.011), history of smoking (OR, 14.285; 95% CI: 1.577-25.000; P = 0.018), maximum body temperature at admission (OR, 8.999; 95% CI: 1.036-78.147, P = 0.046), respiratory failure (OR, 8.772, 95% CI: 1.942-40.000; P = 0.016), albumin (OR, 7.353, 95% CI: 1.098-50.000; P = 0.003), and C-reactive protein (OR, 10.530; 95% CI: 1.224-34.701, P = 0.028) were risk factors for disease progression. CONCLUSIONS: Several factors that led to the progression of COVID-19 pneumonia were identified, including age, history of smoking, maximum body temperature on admission, respiratory failure, albumin, C-reactive protein. These results can be used to further enhance the ability of management of COVID-19 pneumonia.",2020,"Liu, Wei; Tao, Zhao-Wu; Lei, Wang; Ming-Li, Yuan; Kui, Liu; Ling, Zhou; Shuang, Wei; Yan, Deng; Jing, Liu; Liu, Hui-Guo; Ming, Yang; Yi, Hu",Chin Med J (Engl),2370051937,#3344,True
32b10bf8534bb8843320576bbf033d983e89f692,CZI,Letter to the editor: Plenty of coronaviruses but no SARS-CoV-2,10.2807/1560-7917.ES.2020.25.8.2000171,,,cc-by,,2020,"Colson, Philippe; Scola, Bernard La; Esteves-Vieira, Vera; Ninove, Laetitia; Zandotti, Christine; Jimeno, Marie-Thérèse; Gazin, Céline; Bedotto, Marielle; Filosa, Véronique; Giraud-Gatineau, Audrey; Chaudet, Hervé; Brouqui, Philippe; Lagier, Jean-Christophe; Raoult, Didier",Eurosurveillance,1979783167,#2657,True
63af0d8b639b0abe14d9be9eaa3a135bb9a9eaf1,CZI,High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa,10.1038/s41368-020-0074-x,,,cc-by,"It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. To investigate the potential route of 2019-nCov infection on the mucosa of oral cavity, bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas (TCGA) and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression (FANTOM5 CAGE) dataset were collected. RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA and 14 organ types with normal tissues from FANTOM5 CAGE were analyzed in order to explore and validate the expression of ACE2 on the mucosa of oral cavity. Further, single-cell transcriptomes from an independent data generated in-house were used to identify and confirm the ACE2-expressing cell composition and proportion in oral cavity. The results demonstrated that the ACE2 expressed on the mucosa of oral cavity. Interestingly, this receptor was highly enriched in epithelial cells of tongue. Preliminarily, those findings have explained the basic mechanism that the oral cavity is a potentially high risk for 2019-nCoV infectious susceptibility and provided a piece of evidence for the future prevention strategy in dental clinical practice as well as daily life.",2020,"Xu, Hao; Zhong, Liang; Deng, Jiaxin; Peng, Jiakuan; Dan, Hongxia; Zeng, Xin; Li, Taiwen; Chen, Qianming",International Journal of Oral Science,2140051496,#1738,True
1ddf28f6c2bc0a7db607b0771748e34fb6659f51,CZI,Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses,10.3389/fmicb.2020.00298,,,cc-by,"Seven coronaviruses (CoVs) have been isolated from humans so far. Among them, three emerging pathogenic CoVs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and a newly identified CoV (2019-nCoV), once caused or continue to cause severe infections in humans, posing significant threats to global public health. SARS-CoV infection in humans (with about 10% case fatality rate) was first reported from China in 2002, while MERS-CoV infection in humans (with about 34.4% case fatality rate) was first reported from Saudi Arabia in June 2012. 2019-nCoV was first reported from China in December 2019, and is currently infecting more than 70000 people (with about 2.7% case fatality rate). Both SARS-CoV and MERS-CoV are zoonotic viruses, using bats as their natural reservoirs, and then transmitting through intermediate hosts, leading to human infections. Nevertheless, the intermediate host for 2019-nCoV is still under investigation and the vaccines against this new CoV have not been available. Although a variety of vaccines have been developed against infections of SARS-CoV and MERS-CoV, none of them has been approved for use in humans. In this review, we have described the structure and function of key proteins of emerging human CoVs, overviewed the current vaccine types to be developed against SARS-CoV and MERS-CoV, and summarized recent advances in subunit vaccines against these two pathogenic human CoVs. These subunit vaccines are introduced on the basis of full-length spike (S) protein, receptor-binding domain (RBD), non-RBD S protein fragments, and non-S structural proteins, and the potential factors affecting these subunit vaccines are also illustrated. Overall, this review will be helpful for rapid design and development of vaccines against the new 2019-nCoV and any future CoVs with pandemic potential. This review was written for the topic of Antivirals for Emerging Viruses: Vaccines and Therapeutics in the Virology section of Frontiers in Microbiology.",2020,"Du, Ning Wang; Jian, Shang; Shibo, Jiang; Lanying",Frontiers in Microbiology,2169912260,#2793,True
e5d10e5272dca2d3de5ec969be8df777adee2aa3,CZI,Novel coronavirus 2019 (COVID-19): Emergence and implications for emergency care,10.1002/emp2.12034,,,cc-by-nc-nd,"Abstract A novel coronavirus (COVID-19) causing acute illness with severe symptoms has been isolated in Wuhan, Hubei Province, China. Since its emergence, cases have been found worldwide, reminiscent of severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks over the past 2 decades. Current understanding of this epidemic remains limited due to its rapid development and available data. While occurrence outside mainland China remains low, the likelihood of increasing cases globally continues to rise. Given this potential, it is imperative that emergency clinicians understand the preliminary data behind the dynamics of this disease, recognize possible presentations of patients, and understand proposed treatment modalities.",2020,"Yee, Jane; Unger, Lucy; Zadravecz, Frank; Cariello, Paloma; Seibert, Allan; Johnson, Michael Austin; Fuller, Matthew Joseph",Journal of the American College of Emergency Physicians Open,3005586004,#1442,False
9788dc8167b08ed6cfba73a0a4606b5e53bc5e37,CZI,Emerging zoonoses: A one health challenge,10.1016/j.eclinm.2020.100300,,,cc-by,,2020,,EClinicalMedicine,2151572120,#4340,False
801bdee04f820908695b58d1d23a04d3ecbf103f,CZI,Finding equipoise: CEPI revises its equitable access policy,10.1016/j.vaccine.2019.12.055,,,cc-by-nc-nd,"Launched at Davos in January 2017 with funding from sovereign investors and philanthropic institutions, the Coalition for Epidemic Preparedness Innovations (CEPI) is an innovative partnership between public, private, philanthropic, and civil organisations whose mission is to stimulate, finance and co-ordinate vaccine development against diseases with epidemic potential in cases where market incentives fail. As of December 2019, CEPI has committed to investing up to $706 million in vaccine development. This includes 19 vaccine candidates against its priority pathogens (Lassa fever virus, Middle East respiratory syndrome coronavirus, Nipah virus, Chikungunya, Rift Valley fever) and three vaccine platforms to develop vaccines against Disease X, a novel or unanticipated pathogen. As an entity largely supported by public funds, ensuring equitable access to vaccines whose development it supports in low- and middle-income countries is CEPI’s primary focus. CEPI developed an initial equitable access policy shortly after its formation, with key stakeholders expressing strong views about its content and prescriptive nature. The CEPI board instructed that it be revisited after a year. This paper describes the process of revising the policy, and how key issues were resolved. CEPI will continue to take an iterative, rather than prescriptive, approach to its policy—one that reflects the needs of multiple stakeholders and ensures it can meet its equitable access goals.",2020,"Huneycutt, Brenda; Lurie, Nicole; Rotenberg, Sara; Wilder, Richard; Hatchett, Richard",Vaccine,3003629790,#1835,True
8bcd1c3897124adec322dffb8a315fc4e24cb17e,CZI,Origin and evolution of pathogenic coronaviruses,10.1038/s41579-018-0118-9,,30531947,cc-by,"Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs.",2019,"Cui, Jie; Li, Fang; Shi, Zheng-Li",Nat Rev Microbiol,2903899730,#1405,True
606233835c3d6d195b7d230745ccb0fded626aa7,CZI,"Distribution of the COVID-19 epidemic and correlation with population emigration from wuhan, China",10.1097/CM9.0000000000000782,,32118644,cc-by-nc-nd,"BACKGROUND: The ongoing new coronavirus pneumonia (Corona Virus Disease 2019, COVID-19) outbreak is spreading in China, but it has not yet reached its peak. Five million people emigrated from Wuhan before lockdown, potentially representing a source of virus infection. Determining case distribution and its correlation with population emigration from Wuhan in the early stage of the epidemic is of great importance for early warning and for the prevention of future outbreaks. METHODS: The official case report on the COVID-19 epidemic was collected as of January 30, 2020. Time and location information on COVID-19 cases was extracted and analyzed using ArcGIS and WinBUGS software. Data on population migration from Wuhan city and Hubei province were extracted from Baidu Qianxi, and their correlation with the number of cases was analyzed. RESULTS: The COVID-19 confirmed and death cases in Hubei province accounted for 59.91% (5806/9692) and 95.77% (204/213) of the total cases in China respectively. Hot spot provinces included Sichuan and Yunnan, which are adjacent to Hubei. The time risk of Hubei province on the following day was 1.960 times that on the previous day. The number of cases in some cities was relatively low, but the time risk appeared to be continuously rising. The correlation coefficient between the provincial number of cases and emigration from Wuhan was up to 0.943. The lockdown of 17 cities in Hubei province and the implementation of nationwide control measures efficiently prevented an exponential growth in the number of cases. CONCLUSIONS: The population that emigrated from Wuhan was the main infection source in other cities and provinces. Some cities with a low number of cases showed a rapid increase in case load. Owing to the upcoming Spring Festival return wave, understanding the risk trends in different regions is crucial to ensure preparedness at both the individual and organization levels and to prevent new outbreaks.",2020,"Chen, Ze-Liang; Zhang, Qi; Lu, Yi; Guo, Zhong-Min; Zhang, Xi; Zhang, Wen-Jun; Guo, Cheng; Liao, Cong-Hui; Li, Qian-Lin; Han, Xiao-Hu; Lu, Jia-Hai",Chin Med J (Engl),3005811358,#3436,True
919c524f19f79213e6f81aa38502c70287d273dc,CZI,"The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020",10.3390/jcm9020330,,,cc-by,"A cluster of pneumonia cases linked to a novel coronavirus (2019-nCoV) was reported by China in late December 2019. Reported case incidence has now reached the hundreds, but this is likely an underestimate. As of 24 January 2020, with reports of thirteen exportation events, we estimate the cumulative incidence in China at 5502 cases (95% confidence interval: 3027, 9057). The most plausible number of infections is in the order of thousands, rather than hundreds, and there is a strong indication that untraced exposures other than the one in the epidemiologically linked seafood market in Wuhan have occurred.",2020,"Nishiura, Hiroshi; Jung, Sung-mok; Linton, Natalie M.; Kinoshita, Ryo; Yang, Yichi; Hayashi, Katsuma; Kobayashi, Tetsuro; Yuan, Baoyin; Akhmetzhanov, Andrei R.",Journal of Clinical Medicine,3001423274,#52,True
8fb937ce37aa1ad36478e6bc9c1df60d7f594f78,CZI,The coronavirus outbreak: the central role of primary care in emergency preparedness and response,10.3399/bjgpopen20X101041,,31992543,cc-by,,2020,"Dunlop, C.; Howe, A.; Li, D.; Allen, L. N.",BJGP open,3004394961,#231,True
7721a5991adb22000506b40f511a800f879d5914,CZI,Fear of the novel coronavirus,10.3855/jidc.12496,,,cc-by,,2020,"Kelvin, D. J.; Rubino, S.",Journal of Infection in Developing Countries,3004434794,#1613,True
147de820d90c0ce89fb5ae6836ea1794b808fdf2,CZI,Voice from China: nomenclature of the novel coronavirus and related diseases,10.1097/CM9.0000000000000787,,32118646,cc-by-nc-nd,,2020,,Chin Med J (Engl),2966143089,#3475,True
b6b8a2c0c3b83decefa4174ba17271c7cad45c5b,CZI,COVID-19 R0: Magic number or conundrum?,10.4081/idr.2020.8516,,,cc-by-nc,"There is an increasing concern about COVID-19 worldwide. This is a new emerging infectious disease caused by a novel coronavirus (SARS-CoV-2), which recently broke out from the Chinese city of Wuhan and has quickly spread in China, with sporadic cases in each continent [...].",2020,"Petrosillo, Giulio Viceconte; Nicola",Infectious Disease Reports,3006407045,#1946,True
376a81a940b9cdc1b10609164d5b1a5edac60956,CZI,Virus emergentes y reemergentes: un nuevo reto para la salud mundial del milenio,10.1016/j.ram.2020.02.001,,,cc-by-nc-nd,,2020,"Cuestas, María Lujan; Minassian, María Laura",Revista Argentina de Microbiología,2136639808,#2653,True
46bf124930f3ef18bc9dd2d4ae356a45d3bae461,CZI,Chest Radiographic and CT Findings of the 2019 Novel Coronavirus Disease (COVID-19): Analysis of Nine Patients Treated in Korea,10.3348/kjr.2020.0132,,32100485,cc-by-nc,"OBJECTIVE: This study presents a preliminary report on the chest radiographic and computed tomography (CT) findings of the 2019 novel coronavirus disease (COVID-19) pneumonia in Korea. MATERIALS AND METHODS: As part of a multi-institutional collaboration coordinated by the Korean Society of Thoracic Radiology, we collected nine patients with COVID-19 infections who had undergone chest radiography and CT scans. We analyzed the radiographic and CT findings of COVID-19 pneumonia at baseline. Fisher's exact test was used to compare CT findings depending on the shape of pulmonary lesions. RESULTS: Three of the nine patients (33.3%) had parenchymal abnormalities detected by chest radiography, and most of the abnormalities were peripheral consolidations. Chest CT images showed bilateral involvement in eight of the nine patients, and a unilobar reversed halo sign in the other patient. In total, 77 pulmonary lesions were found, including patchy lesions (39%), large confluent lesions (13%), and small nodular lesions (48%). The peripheral and posterior lung fields were involved in 78% and 67% of the lesions, respectively. The lesions were typically ill-defined and were composed of mixed ground-glass opacities and consolidation or pure ground-glass opacities. Patchy to confluent lesions were primarily distributed in the lower lobes (p = 0.040) and along the pleura (p < 0.001), whereas nodular lesions were primarily distributed along the bronchovascular bundles (p = 0.006). CONCLUSION: COVID-19 pneumonia in Korea primarily manifested as pure to mixed ground-glass opacities with a patchy to confluent or nodular shape in the bilateral peripheral posterior lungs. A considerable proportion of patients with COVID-19 pneumonia had normal chest radiographs.",2020,"Yoon, Soon Ho; Lee, Kyung Hee; Kim, Jin Yong; Lee, Young Kyung; Ko, Hongseok; Kim, Ki Hwan; Park, Chang Min; Kim, Yun Hyeon",Korean J Radiol,3006643024,#2077,True
d13a685f861b0f1ba05afa6e005311ad1820fd3a,CZI,Chinese medical staff request international medical assistance in fighting against COVID-19,10.1016/S2214-109X(20)30065-6,,,cc-by,,2020,"Zeng, Yingchun; Zhen, Yan",The Lancet Global Health,2794878804,#1729,False
1ffc99bb608ef7b8ac94ed926b1025a96f8871d9,CZI,How African migrants in China cope with barriers to health care,10.1016/S2468-2667(20)30048-7,,,cc-by-nc-nd,,2020,"Bodomo, Adams; Liem, Andrian; Lin, Lavinia; Hall, Brian J.",The Lancet Public Health,2200321211,#2733,False
c8cdc074d17ad030e2de3393193a5f5afeac4ccf,CZI,Coronavirus outbreak: the role of companies in preparedness and responses,10.1016/S2468-2667(20)30051-7,,,cc-by-nc-nd,"As in previous health crises, the coronavirus disease 2019 (COVID-19) outbreak has raised questions about preparedness and emergency responses in many countries. In this crisis, what role can companies play? Public and private companies must continue to produce or provide their services, but with consideration of the health context. Many companies are involved with the COVID-19 outbreak because they are established in or work with China (client or supplier), and most have already activated their business continuity planning or equivalent. During an infectious disease outbreak like COVID-19, most large companies around the world have a major part to play, especially in terms of preparedness and emergency response. Indeed, companies should be integrated into the governmental health contingency plan developed in many countries, and by WHO and the International Labor Organization. Helped by their occupational practitioners, healthcare advisers, and safety professionals, companies that have a financial capacity and responsibilities (including governmental, federal, or state administrations) will thus have to prepare their business continuity planning for when cases of infected patients occur in the company. They also must be prepared for the potential psychosocial and psychological effects of outbreaks. All health professionals should be involved in the development and implementation of recommendations for companies and their environments",,"Fadel, Marc; Salomon, Jérôme; Descatha, Alexis",The Lancet Public Health,3004394961,#2985,False
46ef984b54bda15d5f23858a2d0a0eb64f39f5d8,CZI,Caring for persons in detention suffering with mental illness during the Covid-19 outbreak,10.1016/j.fsiml.2020.100013,,,cc-by-nc-nd,,2020,"Liebrenz, M.; Bhugra, D.; Buadze, A.; Schleifer, R.",Forensic Science International: Mind and Law,2057404917,#2194,True
99f2888fb4a7fd7ab3cb2e7e9f43f66f7e6a23ce,CZI,"Quantifying the association between domestic travel and the exportation of novel coronavirus (2019-nCoV) cases from Wuhan, China in 2020: A correlational analysis",10.1093/jtm/taaa022,,,pd,,2020,"Zhao, Shi; Zhuang, Zian; Cao, Peihua; Ran, Jinjun; Gao, Daozhou; Lou, Yijun; Yang, Lin; Cai, Yongli; Wang, Weiming; He, Daihai; Wang, Maggie H.",Journal of Travel Medicine,3003807992,#1424,True
b8daf6d2ca5045194115bf8e9f41819cd3e5b47a,CZI,Clinical presentation and outcomes of long-term care residents with coronavirus respiratory infection: A retrospective cohort study,10.1093/ofid/ofz360.2126,,,cc-by-nc-nd,"Background. Human coronaviruses (CoVs) are a major cause of respiratory infection and institutional outbreaks, yet the epidemiology and clinical outcomes of these viruses is poorly described among the elderly residing in long-term care facilities (LTCFs). Methods. We performed a retrospective cohort study of LTCF residents with positive nasopharyngeal or mid-turbinate swabs for CoVs (OC43, 229E, NL63 and HKU1) between January 2013 and December 2018. Demographic and clinical data were obtained from resident charts including clinical presentation, treatment, outcome, and transmission to other residents. Variables were compared using univariate analysis. Results. 3268 residents met inclusion criteria (median age 93 years, 90% male) comprising 7.5% (246/3268) of all positive respiratory virus specimens detected during the study period. 97(39%) of cases were associated with a respiratory outbreak while 149(61%) were sporadic cases that did not result in transmission. OC43 (52%) was the most commonly identified CoV and was more commonly associated with outbreak cases (76% vs. 37%; P < 0.001). In total, 87% of all cases had two or more of runny nose/ congestion, cough, sore throat/hoarse voice or fever. The most common symptoms among residents were cough (85%), runny nose/congestion (79%), and sore throat/ hoarse voice (59%) and only 17% of residents had a measured temperature of ≥ 37.8C. Only 6% of residents received antibiotic treatment for suspected secondary bacterial pneumonia. The 30-day mortality rate was 3.7% with 67% of deaths attributable to the CoV infection. There was no statistically significant difference in symptoms, treatment or outcomes associated with outbreaks or seasonality. Conclusion. CoVs make up an important proportion of respiratory viral infections among LTCF residents and may result in frequent outbreaks. Most residents remain afebrile and have self-limited illness while only a small minority develop secondary bacterial pneumonia and death. Given these findings the benefits of control measures should be weighed against the impact on resident quality of life.",2019,"Williams, V. R.; Pajak, D.; Salt, N.; Leis, J. A.",Open Forum Infectious Diseases,2981463336,#149,False
78360444f3b4540339efc9e7e5f2610a7e46c023,CZI,Q&A: The novel coronavirus outbreak causing COVID-19,10.1186/s12916-020-01533-w,,,cc-by,"What is COVID-19, and what do we know so far about its clinical presentation? The virus responsible for COVID-19, SARS-CoV-2, is in the species SARS-like corona viruses. At 125 nm, it is slightly larger than influenza, SARS and MERS viruses. It is almost certainly a descendant from a bat corona virus of which there are many. The closest is a virus that originated from the Rhinolophus bat which is > 96% homologous with the current SARS-CoV-2 virus. It is only 79% homologous with the original SARS CoV [1]. The near identical gene sequences of 90 analysed cases from outside of China suggests it has likely emerged after a solitary species jump in early December 2019 from an unknown (likely mammalian) intermediate host [2]. Pangolins are an endangered ant-eating mammal from which scientists in Guangzhou have shown a coronavirus with 99% homology, with a receptor binding domain identical to that of SARS-CoV-2. However, this has not been confirmed, and, in addition, the pangolin's rarity means this may not be the only mammal involved.",2020,"Heymann, Dale Fisher; David",BMC Medicine,3005943294,#2807,True
af000c5a8e181550fd16291e5d4f0f70ca9161a1,CZI,"First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020",10.2807/1560-7917.ES.2020.25.6.2000094,,,cc-by,"A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) causing a cluster of respiratory infections (coronavirus disease 2019, COVID-19) in Wuhan, China, was identified on 7 January 2020. The epidemic quickly disseminated from Wuhan and as at 12 February 2020, 45,179 cases have been confirmed in 25 countries, including 1,116 deaths. Strengthened surveillance was implemented in France on 10 January 2020 in order to identify imported cases early and prevent secondary transmission. Three categories of risk exposure and follow-up procedure were defined for contacts. Three cases of COVID-19 were confirmed on 24 January, the first cases in Europe. Contact tracing was immediately initiated. Five contacts were evaluated as at low risk of exposure and 18 at moderate/high risk. As at 12 February 2020, two cases have been discharged and the third one remains symptomatic with a persistent cough, and no secondary transmission has been identified. Effective collaboration between all parties involved in the surveillance and response to emerging threats is required to detect imported cases early and to implement adequate control measures.",2020,"Stoecklin, Sibylle Bernard; Rolland, Patrick; Silue, Yassoungo; Mailles, Alexandra; Campese, Christine; Simondon, Anne; Mechain, Matthieu; Meurice, Laure; Nguyen, Mathieu; Bassi, Clément; Yamani, Estelle; Behillil, Sylvie; Ismael, Sophie; Nguyen, Duc; Malvy, Denis; Lescure, François Xavier; Georges, Scarlett; Lazarus, Clément; Tabaï, Anouk; Stempfelet, Morgane; Enouf, Vincent; Coignard, Bruno; Levy-Bruhl, Daniel; team, Investigation",Eurosurveillance,3006007867,#868,True
95cc4248c19a3cc9a54ebcfa09fc7c80518dac5d,CZI,Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods,10.1016/j.apsb.2020.02.008,,,cc-by-nc-nd,"SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.",2020,"Wu, Canrong; Liu, Yang; Yang, Yueying; Zhang, Peng; Zhong, Wu; Wang, Yali; Wang, Qiqi; Xu, Yang; Li, Mingxue; Li, Xingzhou; Zheng, Mengzhu; Chen, Lixia; Li, Hua",Acta Pharmaceutica Sinica B,2763848918,#2121,True
4faf34d795e5ff74a886528e46268af783fe712b,CZI,Structure analysis of the receptor binding of 2019-nCoV,10.1016/j.bbrc.2020.02.071,,,cc-by,"2019-nCoV is a newly identified coronavirus with high similarity to SARS-CoV. We performed a structural analysis of the receptor binding domain (RBD) of spike glycoprotein responsible for entry of coronaviruses into host cells. The RBDs from the two viruses share 72% identity in amino acid sequences, and molecular simulation reveals highly similar ternary structures. However, 2019-nCoV has a distinct loop with flexible glycyl residues replacing rigid prolyl residues in SARS-CoV. Molecular modeling revealed that 2019-nCoV RBD has a stronger interaction with angiotensin converting enzyme 2 (ACE2). A unique phenylalanine F486 in the flexible loop likely plays a major role because its penetration into a deep hydrophobic pocket in ACE2. ACE2 is widely expressed with conserved primary structures throughout the animal kingdom from fish, amphibians, reptiles, birds, to mammals. Structural analysis suggests that ACE2 from these animals can potentially bind RBD of 2019-nCoV, making them all possible natural hosts for the virus. 2019-nCoV is thought to be transmitted through respiratory droplets. However, since ACE2 is predominantly expressed in intestines, testis, and kidney, fecal-oral and other routes of transmission are also possible. Finally, antibodies and small molecular inhibitors that can block the interaction of ACE2 with RBD should be developed to combat the virus.",2020,"Chen, Yun; Guo, Yao; Pan, Yihang; Zhao, Zhizhuang Joe",Biochemical and Biophysical Research Communications,3006594788,#1158,True
a6eb398b44cfa0686f072f5cdbd07372587f0ed0,CZI,Wuhan coronavirus (2019-nCoV): The need to maintain regular physical activity while taking precautions,10.1016/j.jshs.2020.02.001,,,cc-by-nc-nd,,2020,"Chen, Peijie; Mao, Lijuan; Nassis, George P.; Harmer, Peter; Ainsworth, Barbara E.; Li, Fuzhong",Journal of Sport and Health Science,3004629033,#1208,True
b921ec0b4974533423b7af989620ff4ccc5e2f79,CZI,Characterization of novel monoclonal antibodies against MERS-coronavirus spike protein,10.1016/j.virusres.2020.197863,,31945421,cc-by-nc-nd,"Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes severe pulmonary infection, with approximately 35% mortality. Spike glycoprotein (S) of MERS-CoV is a key target for vaccines and therapeutics because S mediates viral entry and membrane-fusion to host cells. Here, four different S subunit proteins, receptor-binding domain (RBD; 358-606 aa), S1 (1-751 aa), S2 (752-1296 aa), and SDeltaTM (1-1296 aa), were generated using the baculoviral system and immunized in mice to develop neutralizing antibodies. We developed 77 hybridomas and selected five neutralizing mAbs by immunization with SDeltaTM against MERS-CoV EMC/2012 strain S-pseudotyped lentivirus. However, all five mAbs did not neutralize the pseudotyped V534A mutation. Additionally, one mAb RBD-14F8 did not show neutralizing activity against pseudoviruses with amino acid substitution of L506 F or D509 G (England1 strain, EMC/2012 L506 F, and EMC/2012 D509 G), and RBD-43E4 mAb could not neutralize the pseudotyped I529 T mutation, while three other neutralizing mAbs showed broad neutralizing activity. This implies that the mutation in residue 506-509, 529, and 534 of S is critical to generate neutralization escape variants of MERS-CoV. Interestingly, all five neutralizing mAbs have binding affinity to RBD, although most mAbs generated by RBD did not have neutralizing activity. Additionally, chimeric antibodies of RBD-14F8 and RBD-43E4 with human Fc and light chain showed neutralizing effect against wild type MERS-CoV KOR/KNIH/002, similar to the original mouse mAbs. Thus, our mAbs can be utilized for the identification of specific mutations of MERS-CoV.",2020,"Goo, J.; Jeong, Y.; Park, Y. S.; Yang, E.; Jung, D. I.; Rho, S.; Park, U.; Sung, H.; Park, P. G.; Choi, J. A.; Seo, S. H.; Cho, N. H.; Lee, H.; Lee, J. M.; Kim, J. O.; Song, M.",Virus research,2999847588,#35,True
a3e8cfc509af101c522d4193c8917d6e8f68b37b,CZI,"Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series",10.1136/bmj.m606,,,cc-by-nc,"Objective To study the clinical characteristics of patients in Zhejiang province, China, infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) responsible for coronavirus disease 2019 (covid-2019).Design Retrospective case series.Setting Seven hospitals in Zhejiang province, China.Participants 62 patients admitted to hospital with laboratory confirmed SARS-Cov-2 infection. Data were collected from 10 January 2020 to 26 January 2020.Main outcome measures Clinical data, collected using a standardised case report form, such as temperature, history of exposure, incubation period. If information was not clear, the working group in Hangzhou contacted the doctor responsible for treating the patient for clarification.Results Of the 62 patients studied (median age 41 years), only one was admitted to an intensive care unit, and no patients died during the study. According to research, none of the infected patients in Zhejiang province were ever exposed to the Huanan seafood market, the original source of the virus; all studied cases were infected by human to human transmission. The most common symptoms at onset of illness were fever in 48 (77%) patients, cough in 50 (81%), expectoration in 35 (56%), headache in 21 (34%), myalgia or fatigue in 32 (52%), diarrhoea in 3 (8%), and haemoptysis in 2 (3%). Only two patients (3%) developed shortness of breath on admission. The median time from exposure to onset of illness was 4 days (interquartile range 3-5 days), and from onset of symptoms to first hospital admission was 2 (1-4) days.Conclusion As of early February 2020, compared with patients initially infected with SARS-Cov-2 in Wuhan, the symptoms of patients in Zhejiang province are relatively mild.",2020,"Xu, Xiao-Wei; Wu, Xiao-Xin; Jiang, Xian-Gao; Xu, Kai-Jin; Ying, Ling-Jun; Ma, Chun-Lian; Li, Shi-Bo; Wang, Hua-Ying; Zhang, Sheng; Gao, Hai-Nv; Sheng, Ji-Fang; Cai, Hong-Liu; Qiu, Yun-Qing; Li, Lan-Juan",BMJ,3001118548,#1262,True
58be092086c74c58e9067121a6ba4836468e7ec3,CZI,The Author's Response: Case of the Index Patient Who Caused Tertiary Transmission of Coronavirus Disease 2019 in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Pneumonia Monitored by Quantitative RT-PCR,10.3346/jkms.2020.35.e89,,32080993,cc-by-nc,,2020,"Lim, Jaegyun; Jeon, Seunghyun; Shin, Hyun Young; Kim, Moon Jung; Seong, Yu Min; Lee, Wang Jun; Choe, Kang Won; Kang, Yu Min; Lee, Baeckseung; Park, Sang Joon",J Korean Med Sci,3005657121,#1576,True
80993091f576dc7fdbec10552b45b4af5eec2b8b,CZI,"Short-term Forecasts of the COVID-19 Epidemic in Guangdong and Zhejiang, China: February 13–23, 2020",10.3390/jcm9020596,,,cc-by,"The ongoing COVID-19 epidemic continues to spread within and outside of China, despite several social distancing measures implemented by the Chinese government. Limited epidemiological data are available, and recent changes in case definition and reporting further complicate our understanding of the impact of the epidemic, particularly in the epidemic&rsquo;s epicenter. Here we use previously validated phenomenological models to generate short-term forecasts of cumulative reported cases in Guangdong and Zhejiang, China. Using daily reported cumulative case data up until 13 February 2020 from the National Health Commission of China, we report 5- and 10-day ahead forecasts of cumulative case reports. Specifically, we generate forecasts using a generalized logistic growth model, the Richards growth model, and a sub-epidemic wave model, which have each been previously used to forecast outbreaks due to different infectious diseases. Forecasts from each of the models suggest the outbreaks may be nearing extinction in both Guangdong and Zhejiang; however, the sub-epidemic model predictions also include the potential for further sustained transmission, particularly in Zhejiang. Our 10-day forecasts across the three models predict an additional 65&ndash;81 cases (upper bounds: 169&ndash;507) in Guangdong and an additional 44&ndash;354 (upper bounds: 141&ndash;875) cases in Zhejiang by February 23, 2020. In the best-case scenario, current data suggest that transmission in both provinces is slowing down.",2020,"Roosa, Kimberlyn; Lee, Yiseul; Luo, Ruiyan; Kirpich, Alexander; Rothenberg, Richard; Hyman, M. James; Yan, Ping; Chowell, Gerardo",Journal of Clinical Medicine,,#1506,True
74ef189f090e07b5df4d7367b09fd4859c3f01b1,CZI,COVID-19 and artificial intelligence: protecting health-care workers and curbing the spread,10.1016/S2589-7500(20)30054-6,,,cc-by,,2020,"McCall, Becky",The Lancet Digital Health,2904251400,#1375,False
459c780b398aa89f292490a6b455845448b7d537,CZI,In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus,10.1016/j.joim.2020.02.005,,,cc-by-nc-nd,"Objective In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus (2019-nCoV), an ongoing novel coronavirus that causes pneumonia. Methods There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database. Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion (ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV interaction. In the second step we searched Chinese herbal databases to identify treatments containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb. Results Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these 26 treatments were related to regulating viral infection, immune/inflammation reactions and hypoxia response. Conclusion Chinese herbal treatments classically used for treating viral respiratory infection might contain direct anti-2019-nCoV compounds.",2020,"Zhang, Deng-hai; Wu, Kun-lun; Zhang, Xue; Deng, Sheng-qiong; Peng, Bin",Journal of Integrative Medicine,1577002143,#1346,True
519cc50b5527635a0a05f7efe73b2f30c62d9936,CZI,The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2,10.1038/s41564-020-0695-z,,,cc-by,"The present outbreak of a coronavirus-associated acute respiratory disease called coronavirus disease 19 (COVID-19) is the third documented spillover of an animal coronavirus to humans in only two decades that has resulted in a major epidemic. The Coronaviridae Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the classification of viruses and taxon nomenclature of the family Coronaviridae, has assessed the placement of the human pathogen, tentatively named 2019-nCoV, within the Coronaviridae. Based on phylogeny, taxonomy and established practice, the CSG recognizes this virus as forming a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus, and designates it as SARS-CoV-2. In order to facilitate communication, the CSG proposes to use the following naming convention for individual isolates: SARS-CoV-2/host/location/isolate/date. While the full spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined, the independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying viruses at the species level to complement research focused on individual pathogenic viruses of immediate significance. This will improve our understanding of virus–host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.",2020,"Gorbalenya, Alexander E.; Baker, Susan C.; Baric, Ralph S.; de Groot, Raoul J.; Drosten, Christian; Gulyaeva, Anastasia A.; Haagmans, Bart L.; Lauber, Chris; Leontovich, Andrey M.; Neuman, Benjamin W.; Penzar, Dmitry; Perlman, Stanley; Poon, Leo L. M.; Samborskiy, Dmitry V.; Sidorov, Igor A.; Sola, Isabel; Ziebuhr, John; Coronaviridae Study Group of the International Committee on Taxonomy of, Viruses",Nature Microbiology,3005788786,#3173,True
b36310af655a9ba95c32c0d8e88e5fb445edb7a1,CZI,"Transmission potential of the novel coronavirus (COVID-19) onboard the Diamond Princess Cruises Ship, 2020",10.1016/j.idm.2020.02.003,,,cc-by-nc-nd,"An outbreak of COVID-19 developed aboard the Princess Cruises Ship during January-February 2020. Using mathematical modeling and time-series incidence data describing the trajectory of the outbreak among passengers and crew members, we characterize how the transmission potential varied over the course of the outbreak. Our estimate of the mean reproduction number in the confined setting reached values as high as ∼11, which is higher than mean estimates reported from community-level transmission dynamics in China and Singapore (approximate range: 1.1-7). Our findings suggest that Rt decreased substantially compared to values during the early phase after the Japanese government implemented an enhanced quarantine control. Most recent estimates of Rt reached values largely below the epidemic threshold, indicating that a secondary outbreak of the novel coronavirus was unlikely to occur aboard the Diamond Princess Ship.",2020,"Mizumoto, Kenji; Chowell, Gerardo",Infectious Disease Modelling,3006223500,#2901,True
a209539267a73a6fb2ed9ea4766a50687b9b8cfb,CZI,Non-invasive respiratory support for patients with novel coronavirus pneumonia: clinical efficacy and reduction in risk of infection transmission,10.1097/CM9.0000000000000761,,32097201,cc-by-nc-nd,,2020,"Xia, Jin-Gen; Zhao, Jian-Ping; Cheng, Zhen-Shun; Hu, Yi; Duan, Jun; Zhan, Qing-Yuan",Chin Med J (Engl),3005079553,#1916,True
2d1374051e0b6d5b8a3f42c4906e0a56ea1d5b9d,CZI,Uncertainties about the transmission routes of 2019 novel coronavirus,10.1111/irv.12735,,,cc-by,"The 2019 novel coronavirus (now named as SARS‐CoV‐2) caused an outbreak of SARS‐like illness in the late of December 2019. At present, the origin, susceptible population, and infection sources already have been clear.1, 2 However, the transmission routes, a key step to the epidemic control, have not yet been fully ascertained. Here, we focus on the potential transmission routes that have been investigated in the SARS‐CoV‐2 epidemic recently. SARS‐CoV‐2, similar to SARS and MERS, is predominantly spread via respiratory tract with high infectivity. It is commonly recognized that droplet transmission is the main route. Spread by aerosol is suspected to be another important route of transmission but unestablished now. Epidemiological experts, as well as the WHO, consider more evidence is needed to confirm.3 Besides, there are other routes except respiratory transmission. The previous study indicated that different human coronaviruses, such as SARS‐CoV and MERS‐CoV, can maintain infectious for a different time on inanimate surfaces.4 Meanwhile, it was reported that SARS‐CoV‐2 was also founded on the surface of the door handles, cell phones, and other items in the residential sites of confirmed cases.5 Therefore, individuals will be probably infected if they touch the nose, mouth, or eyes after contacting the contaminated items.",2020,"Han, Qingmei; Lin, Qingqing; Ni, Zuowei; You, Liangshun",Influenza and Other Respiratory Viruses,3002533591,#4142,False
ccc1cedafbb30ee3184f9fc7999f4aa457805cab,CZI,Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study,10.1016/S2589-7500(20)30026-1,,,cc-by,"Summary Background As the outbreak of coronavirus disease 2019 (COVID-19) progresses, epidemiological data are needed to guide situational awareness and intervention strategies. Here we describe efforts to compile and disseminate epidemiological information on COVID-19 from news media and social networks. Methods In this population-level observational study, we searched DXY.cn, a health-care-oriented social network that is currently streaming news reports on COVID-19 from local and national Chinese health agencies. We compiled a list of individual patients with COVID-19 and daily province-level case counts between Jan 13 and Jan 31, 2020, in China. We also compiled a list of internationally exported cases of COVID-19 from global news media sources (Kyodo News, The Straits Times, and CNN), national governments, and health authorities. We assessed trends in the epidemiology of COVID-19 and studied the outbreak progression across China, assessing delays between symptom onset, seeking care at a hospital or clinic, and reporting, before and after Jan 18, 2020, as awareness of the outbreak increased. All data were made publicly available in real time. Findings We collected data for 507 patients with COVID-19 reported between Jan 13 and Jan 31, 2020, including 364 from mainland China and 143 from outside of China. 281 (55%) patients were male and the median age was 46 years (IQR 35–60). Few patients (13 [3%]) were younger than 15 years and the age profile of Chinese patients adjusted for baseline demographics confirmed a deficit of infections among children. Across the analysed period, delays between symptom onset and seeking care at a hospital or clinic were longer in Hubei province than in other provinces in mainland China and internationally. In mainland China, these delays decreased from 5 days before Jan 18, 2020, to 2 days thereafter until Jan 31, 2020 (p=0·0009). Although our sample captures only 507 (5·2%) of 9826 patients with COVID-19 reported by official sources during the analysed period, our data align with an official report published by Chinese authorities on Jan 28, 2020. Interpretation News reports and social media can help reconstruct the progression of an outbreak and provide detailed patient-level data in the context of a health emergency. The availability of a central physician-oriented social network facilitated the compilation of publicly available COVID-19 data in China. As the outbreak progresses, social media and news reports will probably capture a diminishing fraction of COVID-19 cases globally due to reporting fatigue and overwhelmed health-care systems. In the early stages of an outbreak, availability of public datasets is important to encourage analytical efforts by independent teams and provide robust evidence to guide interventions. Funding Fogarty International Center, US National Institutes of Health.",2020,"Sun, Kaiyuan; Chen, Jenny; Viboud, Cécile",The Lancet Digital Health,3005041554,#1359,True
57df78198df2774be87635b81f850b6eeb2dd6f8,CZI,Measuring multimorbidity beyond counting diseases: systematic review of community and population studies and guide to index choice,10.1136/bmj.m160,,,cc-by,"Objectives To identify and summarise existing indices for measuring multimorbidity beyond disease counts, to establish which indices include mental health comorbidities or outcomes, and to develop recommendations based on applicability, performance, and usage.Design Systematic review.Data sources Seven medical research databases (Medline, Web of Science Core Collection, Cochrane Library, Embase, PsycINFO, Scopus, and CINAHL Plus) from inception to October 2018 and bibliographies and citations of relevant papers. Searches were limited to English language publications.Eligibility criteria for study selection Original articles describing a new multimorbidity index including more information than disease counts and not focusing on comorbidity associated with one specific disease. Studies were of adults based in the community or at population level.Results Among 7128 search results, 5560 unique titles were identified. After screening against eligibility criteria the review finally included 35 papers. As index components, 25 indices used conditions (weighted or in combination with other parameters), five used diagnostic categories, four used drug use, and one used physiological measures. Predicted outcomes included mortality (18 indices), healthcare use or costs (13), hospital admission (13), and health related quality of life (7). 29 indices considered some aspect of mental health, with most including it as a comorbidity. 12 indices are recommended for use.Conclusions 35 multimorbidity indices are available, with differing components and outcomes. Researchers and clinicians should examine existing indices for suitability before creating new ones.Systematic review registration PROSPERO CRD42017074211.",2020,"Stirland, Lucy E.; González-Saavedra, Laura; Mullin, Donncha S.; Ritchie, Craig W.; Muniz-Terrera, Graciela; Russ, Tom C.",BMJ,2080410907,#1244,True
7a07d2f6803fd33f326be4952954b321c8eaaa2b,CZI,Wuhan novel coronavirus 2019nCoV,10.31646/gbio.50,,,cc-by,"Information about the open-access article 'Wuhan novel coronavirus 2019nCoV' in DOAJ. DOAJ is an online directory that indexes and provides access to quality open access, peer-reviewed journals.",2020,"MacIntyre, C Raina",Global Biosecurity,3002186368,#602,True
a6ce4ce12c7af1cfb4d71764b963285b687e6b51,CZI,Assessing the Impact of Reduced Travel on Exportation Dynamics of Novel Coronavirus Infection (COVID-19),10.3390/jcm9020601,,,cc-by,"The impact of the drastic reduction in travel volume within mainland China in January and February 2020 was quantified with respect to reports of novel coronavirus (COVID-19) infections outside China. Data on confirmed cases diagnosed outside China were analyzed using statistical models to estimate the impact of travel reduction on three epidemiological outcome measures: (i) the number of exported cases, (ii) the probability of a major epidemic, and (iii) the time delay to a major epidemic. From 28 January to 7 February 2020, we estimated that 226 exported cases (95% confidence interval: 86,449) were prevented, corresponding to a 70.4% reduction in incidence compared to the counterfactual scenario. The reduced probability of a major epidemic ranged from 7% to 20% in Japan, which resulted in a median time delay to a major epidemic of two days. Depending on the scenario, the estimated delay may be less than one day. As the delay is small, the decision to control travel volume through restrictions on freedom of movement should be balanced between the resulting estimated epidemiological impact and predicted economic fallout.",2020,"Anzai, Asami; Kobayashi, Tetsuro; Linton, M. Natalie; Kinoshita, Ryo; Hayashi, Katsuma; Suzuki, Ayako; Yang, Yichi; Jung, Sung-mok; Miyama, Takeshi; Akhmetzhanov, R. Andrei; Nishiura, Hiroshi",Journal of Clinical Medicine,3005118804,#1873,True
194f563839d8eccfdbc1d7f63a33529c42c96ec2,CZI,Imaging changes of severe COVID-19 pneumonia in advanced stage,10.1007/s00134-020-05990-y,,,cc-by-nc,"We recently reported in Intensive Care Medicine the imaging changes of acute stage from a case of 75-year-old male patient with severe COVID-19 pneumonia combined acute respiratory distress syndrome (ARDS), septic shock, and multiple organ disfunction syndrome (MODS) who had a history of 10-year hypertension and 1-year diabetes. He presently received advanced life support treatment including respiratory support (invasive mechanical ventilation) and circulatory support (vasoconstrictor assistance), as well as intermittent renal replacement therapy (IRRT) in intensive care unit (ICU) of our hospital—a tertiary teaching hospital of medical university. Because his MODS still existed on the day 20 after symptom onset, we had to re-examine the chest computed tomographic (CT). The results showed that early changes of reticular pulmonary fibrosis appeared in Panels D, E, and F (marked by green arrows), compensatory emphysema occurred in Panels D and E (marked by blue arrows), and pulmonary cavity formation appeared in Panel F (marked by blue arrows), compared with acute stage of the day 5 after symptom onset, inflammatory lesions and ground glass shadow of Panels A and B (marked by red arrows), as well as septal line of Panel C (marked by yellow arrows). Presently, this patient is still under the condition of advanced life support therapy (Fig. 1).ER -",2020,"Zhang, Wei",Intensive Care Medicine,3006643024,#3025,False
1f5c1597a84ed1d4f84c488cd19098a091a3d513,CZI,"Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARSCoV-2): Facts and myths",10.1016/j.jmii.2020.02.012,,,cc-by-nc-nd,"Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have been reported in 32 countries/regions, resulting in more than 2,000 deaths worldwide. Despite the fact that most COVID-19 cases and mortalities were reported in China, the WHO has declared this outbreak as the sixth public health emergency of international concern. The COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneumonia. Adults represent the population with the highest infection rate; however, neonates, children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymptomatic carriers are possible. The most common finding on chest imaging among patients with pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely to be older patients with underlying comorbidities compared to mild cases. Indeed, age and disease severity may be correlated with the outcomes of COVID-19. To date, effective treatment is lacking; however, clinical trials investigating the efficacy of several agents, including remdesivir and chloroquine, are underway in China. Currently, effective infection control intervention is the only way to prevent the spread of SARS-CoV-2.",2020,"Lai, Chih-Cheng; Liu, Yen Hung; Wang, Cheng-Yi; Wang, Ya-Hui; Hsueh, Shun-Chung; Yen, Muh-Yen; Ko, Wen-Chien; Hsueh, Po-Ren","Journal of Microbiology, Immunology and Infection",2029688661,#4530,True
b603913495d3cbce15eff09e645007cdf42a6e1b,CZI,Molecular Diagnosis of a Novel Coronavirus (2019-nCoV) Causing an Outbreak of Pneumonia,10.1093/clinchem/hvaa029,,32031583,pd,"BACKGROUND: A novel coronavirus of zoonotic origin (2019-nCoV) has recently been identified in patients with acute respiratory disease. This virus is genetically similar to SARS coronavirus and bat SARS-like coronaviruses. The outbreak was initially detected in Wuhan, a major city of China, but has subsequently been detected in other provinces of China. Travel-associated cases have also been reported in a few other countries. Outbreaks in health care workers indicate human-to-human transmission. Molecular tests for rapid detection of this virus are urgently needed for early identification of infected patients. METHODS: We developed two 1-step quantitative real-time reverse-transcription PCR assays to detect two different regions (ORF1b and N) of the viral genome. The primer and probe sets were designed to react with this novel coronavirus and its closely related viruses, such as SARS coronavirus. These assays were evaluated using a panel of positive and negative controls. In addition, respiratory specimens from two 2019-nCoV-infected patients were tested. RESULTS: Using RNA extracted from cells infected by SARS coronavirus as a positive control, these assays were shown to have a dynamic range of at least seven orders of magnitude (2x10-4-2000 TCID50/reaction). Using DNA plasmids as positive standards, the detection limits of these assays were found to be below 10 copies per reaction. All negative control samples were negative in the assays. Samples from two 2019-nCoV-infected patients were positive in the tests. CONCLUSIONS: The established assays can achieve a rapid detection of 2019n-CoV in human samples, thereby allowing early identification of patients.",2020,"Chu, Daniel K. W.; Pan, Yang; Cheng, Samuel M. S.; Hui, Kenrie P. Y.; Krishnan, Pavithra; Liu, Yingzhi; Ng, Daisy Y. M.; Wan, Carrie K. C.; Yang, Peng; Wang, Quanyi; Peiris, Malik; Poon, Leo L. M.",Clin Chem,3003637715,#545,True
ed3dae51cc8af4b99b820ce4eaf28f9c9995b060,CZI,Are children less susceptible to COVID-19?,10.1016/j.jmii.2020.02.011,,,cc-by-nc-nd,,2020,"Lee, Ping-Ing; Hu, Ya-Li; Chen, Po-Yen; Huang, Yhu-Chering; Hsueh, Po-Ren","Journal of Microbiology, Immunology and Infection",2415654588,#1967,True
96f65d71931741ea4668f2fbcae54a8d8905abac,CZI,From SARS-CoV to 2019-nCoV Outbreak: Similarities in the Early Epidemics and Prediction of Future Trends,10.1097/CM9.0000000000000776,,32118641,cc-by-nc-nd,,2020,"Chen, Ze-Liang; Zhang, Wen-Jun; Lu, Yi; Guo, Cheng; Guo, Zhong-Min; Liao, Cong-Hui; Zhang, Xi; Zhang, Yi; Han, Xiao-Hu; Li, Qian-Lin; Lu, Jia-Hai",Chin Med J (Engl),3002084665,#3435,True
e4b23ec957446463f8d7be44f3ddbbf6155ae10c,CZI,Single-cell RNA sequencing data suggest a role for angiotensin-converting enzyme 2 in kidney impairment in patients infected with 2019-nCoV,10.1097/CM9.0000000000000783,,32118645,cc-by-nc-nd,,2020,"Deng, Yi-Yao; Zheng, Ying; Cai, Guang-Yan; Chen, Xiang-Mei; Hong, Quan",Chin Med J (Engl),2794521141,#3423,True
69ca8c0a79935fbe985f02fc53c1a9da5c42acd3,CZI,Effect of isolation practice on the transmission of middle east respiratory syndrome coronavirus among hemodialysis patients: A 2-year prospective cohort study,10.1097/MD.0000000000018782,,32011472,cc-by-nc-nd,"Hemodialysis (HD) patients had a high rate of infection transmission and mortality during the middle east respiratory syndrome coronavirus (MERS-CoV) outbreak in Saudi Arabia. A standardized guideline on isolation technique for exposed HD patients is not available. Thus, this study aimed to evaluate the effect of different isolation strategies on the prevention of secondary viral transmission and clinical outcomes among exposed HD patients.During the 2015 MERS-CoV outbreak in Korea, 116 patients in 3 HD units were incidentally exposed to individuals with confirmed MERS-CoV infection and underwent different types of isolation, which were as follows: single-room isolation (n = 54, 47%), cohort isolation (n = 46, 40%), and self-imposed quarantine (n = 16, 13%). The primary outcome was rate of secondary viral transmission. The secondary outcome measures were changes in clinical and biochemical markers during the isolation period, difference in clinical and biochemical markers according to the types of isolation practice, and effect of isolation practice on patient survival.During a mean isolation period of 15 days, no further cases of secondary transmission were detected among HD patients. Plasma hemoglobin, serum calcium, and serum albumin levels and single-pool Kt/V decreased during the isolation period but normalized thereafter. Patients who were subjected to self-imposed quarantine had higher systolic and diastolic blood pressure, lower total cholesterol level, and lower Kt/V than those who underwent single-room or cohort isolation. During the 24-month follow-up period, 12 patients died. However, none of the deaths occurred during the isolation period, and no differences were observed in patient survival rate according to different isolation strategies.Although 116 participants in 3 HD units were incidentally exposed to MERS-CoV during the 2015 outbreak in Korea, strict patient surveillance and proper isolation practice prevented secondary transmission of the virus. Thus, a renal disaster protocol, which includes proper contact surveillance and isolation practice, must be established in the future to accommodate the needs of HD patients during disasters or outbreaks.",2020,"Park, Hayne Cho; Lee, Sang-Ho; Kim, Juhee; Kim, Do Hyoung; Cho, AJin; Jeon, Hee Jung; Oh, Jieun; Noh, Jung-Woo; Jeong, Da-Wun; Kim, Yang-Gyun; Lee, Chang-Hee; Yoo, Kyung Don; Lee, Young-Ki",Medicine (Baltimore),3000673943,#287,True
5ba8056230c17ec133169d79aacf61ed7d4b458b,CZI,"The novel coronavirus outbreak in Wuhan, China",10.1186/s41256-020-00135-6,,,cc-by,"The novel coronavirus (2019-nCoV, or COVID-19) epidemic first broke out in Wuhan and has been spreading in whole China and the world. The numbers of new infections and deaths in Wuhan are still increasing, which have posed major public health and governance concerns. A series of mandatory actions have been taken by the municipal and provincial governments supported by the central government, such as measures to restrict travels across cities, case detection and contact tracing, quarantine, guidance and information to the public, detection kit development, etc. Challenges such as lacking effective drugs, insufficient hospital services and medical supplies, logistics, etc. have much alleviated with the solidarity of the whole society. The pandemic will definitely be ended with the continuous efforts of both national and international multi-sectoral bodies.",2020,"Zhu, Hengbo; Wei, Li; Niu, Ping",Global Health Research and Policy,2023898906,#3037,True
861f05718b673306c2044167d92bb31d68a0d9bb,CZI,Tracking online heroisation and blame in epidemics,10.1016/S2468-2667(20)30033-5,,,cc-by,,2020,"Atlani-Duault, Laëtitia; Ward, Jeremy K.; Roy, Melissa; Morin, Céline; Wilson, Andrew",The Lancet Public Health,2804996859,#3217,True
66b67940ae16f657fd93fad230081d20d98c55f7,CZI,A precision medicine approach to managing Wuhan Coronavirus pneumonia,10.1093/pcmedi/pbaa002,,,cc-by-nc,"In December, 2019, several patients with pneumonia of an unknown cause were detected in Wuhan, China. On January 7, 2020, the causal organism was identified as a new coronavirus, later named as the “2019 novel coronavirus” (2019-nCoV). Genome sequencing found the genetic sequence of 2019-nCoV homologous to that of Severe Acute Respiratory Syndrome-Associated Coronavirus (SARS-CoV). As of January 29, 2020, the virus had been diagnosed in more than 7,000 patients in China and 77 outside this country. It is reported that both symptomatic and asymptomatic patients with 2019-nCov can play a role in disease transmission via airborne and contact. This finding has caused a great concern about the prevention of illness spread. The clinical features of the infection are not specific and are often indistinguishable from those of other respiratory infections, making it difficult to diagnose. Given that the virus has a strong ability to spread between individuals, it is of top priority to identify potential or suspected patients as soon as possible. Or the virus may cause a serious pandemic. Therefore, a precision medicine approach to managing this disease is urgently needed for detecting and controlling the spread of the virus. In this article, we present such an approach to managing 2019-nCoV-related pneumonia based on the unique traits of the virus recently revealed, and on our experience with coronaviruses at West China Hospital in Chengdu, China.",2020,"Minjin Wang, Yanbing Zhou, Zhiyong Zong, Zongan Liang, Yu Cao, Hong Tang, Bin Song, Zixing Huang, Yan Kang, Ping Feng, Binwu Ying, Weimin Li",Precision Clinical Medicine,3006495046,#262,True
d666c86af7eeaee9a830f99d863045f52571ea5f,CZI,"Extracorporeal membrane oxygenation support in 2019 novel coronavirus disease: indications, timing, and implementation",10.1097/CM9.0000000000000778,,32118643,cc-by-nc-nd,,2020,"Li, Min; Gu, Si-Chao; Wu, Xiao-Jing; Xia, Jin-Gen; Zhang, Yi; Zhan, Qing-Yuan",Chin Med J (Engl),3005079553,#3360,True
b25291591ed2b529efff2b281c7be556950a256b,CZI,Editor's Note,10.14789/jmj.2020.66.1-en,,,cc-by,"A few years ago, when I wrote an editorial note, there was an unseasonable heavy snowfall,making the city of Tokyo havoc. This time the cause is the 2019 Novel Coronavirus (SARS-CoV-2).Infection by this novel virus had become grave news involving the whole world by the end ofJanuary. Now, as I am writing this, there is no cure, and the number of patients is also increasingday by day in Japan. Masks are out of stock throughout the city, and I have heard that people queueup for few masks in front of drug stores from early in the morning.The effectiveness of wearing a mask to prevent infection is limited. What is the cause of such asituation? As a matter of fact, in an epidemic of infection, the most serious problem is not infectionitself, but unscientific rumors and people who are easily swayed by them. Avoidance of vaccinationby insisting that vaccines have no effect or that they are harmful to the body is fundamentally thesame. The anti-vaccination movement still exists despite the evidence-based medicine, and thereare concerns about its expansion. However, even with scientific evidence, it is not easy to persuadeanti-vaccinationists, and this is the moment, when we, academia, feel powerless.Nevertheless, we should not be discouraged. The mission of academia is to conduct reliableresearch. Reliable data are obtained from such research, and scientific solution of the problemssteadily proceed. Based on the outcomes of these data and solutions, scientists themselves shouldcreate the methods of advocacy and persuasion or rely on experts in this area.However, scientists should solve the problems with science. Academic journals such as theJuntendo Medical Journal may be of marked significance in this regard. It is important to get theexcellent findings, but even negative data need to be published somewhere and shared amongvarious people, whenever they lead to academically important questions. Such data promote thediscussions, deeper research perspectives, and new themes. Submitting articles in English has beenestablished in the Juntendo Medical Journal. The journal will achieve further progress in the nearfuture.Toshihiro MitaDepartment of Tropical Medicine and ParasitologyCall for feature article proposalsTo introduce the latest medical findings, Juntendo Medical Journal features a specific focus areafor each issue. We would like to request all our readers to address any suggestions or proposals forsuitable focus areas to our editorial office.",2020,,Juntendo Medical Journal,2887248870,#3229,False
140e6d0298bfcd1e825a4b81dcabc50d1658357a,CZI,The Novel Coronavirus: A Bird's Eye View,10.15171/ijoem.2020.1921,,32020915,cc-by-nc-sa,"The novel coronavirus (2019-nCoV) outbreak, which initially began in China, has spread to many countries around the globe, with the number of confirmed cases increasing every day. With a death toll exceeding that of the SARS-CoV outbreak back in 2002 and 2003 in China, 2019-nCoV has led to a public health emergency of international concern, putting all health organizations on high alert. Herein, we present on an overview of the currently available information on the pathogenesis, epidemiology, clinical presentation, diagnosis, and treatment of this virus.",2020,"Habibzadeh, Parham; Stoneman, Emily K.",Int J Occup Environ Med,3004735879,#319,True
2aff265697682af71816737a2fd85f1d9bc9a0c4,CZI,The Rate of Underascertainment of Novel Coronavirus (2019-nCoV) Infection: Estimation Using Japanese Passengers Data on Evacuation Flights,10.3390/jcm9020419,,32033064,cc-by,"From 29 to 31 January 2020, a total of 565 Japanese citizens were evacuated from Wuhan, China on three chartered flights. All passengers were screened upon arrival in Japan for symptoms consistent with novel coronavirus (2019-nCoV) infection and tested for presence of the virus. Assuming that the mean detection window of the virus can be informed by the mean serial interval (estimated at 7.5 days), the ascertainment rate of infection was estimated at 9.2% (95% confidence interval: 5.0, 20.0). This indicates that the incidence of infection in Wuhan can be estimated at 20,767 infected individuals, including those with asymptomatic and mildly symptomatic infections. The infection fatality risk (IFR)-the actual risk of death among all infected individuals-is therefore 0.3% to 0.6%, which may be comparable to Asian influenza pandemic of 1957-1958.",2020,"Nishiura, Hiroshi; Kobayashi, Tetsuro; Yang, Yichi; Hayashi, Katsuma; Miyama, Takeshi; Kinoshita, Ryo; Linton, Natalie M.; Jung, Sung-Mok; Yuan, Baoyin; Suzuki, Ayako; Akhmetzhanov, Andrei R.",J Clin Med,3004658686,#536,True
,CZI,"Community Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, Shenzhen, China, 2020",10.3201/eid2606.200239,,32125269,cc-by,"Since early January 2020, after the outbreak of 2019 novel coronavirus infection in Wuhan, China, ≈365 confirmed cases have been reported in Shenzhen, China. The mode of community and intrafamily transmission is threatening residents in Shenzhen. Strategies to strengthen prevention and interruption of these transmissions should be urgently addressed.",2020,"Liu, Jiaye; Liao, Xuejiao; Qian, Shen; Yuan, Jing; Wang, Fuxiang; Liu, Yingxia; Wang, Zhaoqin; Wang, Fu-Sheng; Liu, Lei; Zhang, Zheng",Emerg Infect Dis,2116732940,#3346,
,CZI,Risk for Transportation of 2019 Novel Coronavirus Disease from Wuhan to Other Cities in China,10.3201/eid2605.200146,,32053479,cc-by,"On January 23, 2020, China quarantined Wuhan to contain 2019 novel coronavirus disease (COVID-19). We estimated the probability of transportation of COVID-19 from Wuhan to 369 other cities in China before the quarantine. Expected COVID-19 risk is >50% in 130 (95% CI 89-190) cities and >99% in the 4 largest metropolitan areas.",2020,"Du, Zhanwei; Wang, Lin; Cauchemez, Simon; Xu, Xiaoke; Wang, Xianwen; Cowling, Benjamin J.; Meyers, Lauren Ancel",Emerg Infect Dis,3006320625,#872,
,CZI,Latest assessment on COVID-19 from the European Centre for Disease Prevention and Control (ECDC),10.2807/1560-7917.ES.2020.25.8.2002271,,,cc-by,,2020,"team, Eurosurveillance editorial",Eurosurveillance,,#2535,
,CZI,"COVID-19 in 2 Persons with Mild Upper Respiratory Symptoms on a Cruise Ship, Japan",10.3201/eid2606.200452,,32118533,cc-by,"We describe 2 cases of COVID-19 in patients with mild upper respiratory symptoms. Both patients worked on a cruise ship quarantined off the coast of Japan. One patient had persistent, low-grade upper respiratory tract symptoms without fever. The other patient had rapid symptom cessation but persistent viral RNA detection.",2020,"Arashiro, Takeshi; Furukawa, Keiichi; Nakamura, Akira",Emerging infectious diseases,2108857951,#3520,
,CZI,"Potential Presymptomatic Transmission of SARS-CoV-2, Zhejiang Province, China, 2020",10.3201/eid2605.200198,,32091386,cc-by,"We report a 2-family cluster of persons infected with severe acute respiratory syndrome coronavirus 2 in the city of Zhoushan, Zhejiang Province, China, during January 2020. The infections resulted from contact with an infected but potentially presymptomatic traveler from the city of Wuhan in Hubei Province.",2020,"Tong, Zhen-Dong; Tang, An; Li, Ke-Feng; Li, Peng; Wang, Hong-Ling; Yi, Jing-Ping; Zhang, Yong-Li; Yan, Jian-Bo",Emerg Infect Dis,3006655826,#1754,
,CZI,Ten hot issues of breast cancer under the novel coronavirus,10.0376/cma.j.issn.0376-2491.2020.0002,,32036640,,,2020,"Jiang, Z. F.; Li, J. B.",Zhonghua Yi Xue Za Zhi,3003451419,#615,
,CZI,Coronavirus Infections-More Than Just the Common Cold,10.1001/jama.2020.0757,,,,,2020,"Paules, C. I.; Marston, H. D.; Fauci, A. S.",JAMA - Journal of the American Medical Association,3000834295,#146,
,CZI,"The Novel Coronavirus Originating in Wuhan, China: Challenges for Global Health Governance",10.1001/jama.2020.1097,,31999307,,,2020,"Phelan, A. L.; Katz, R.; Gostin, L. O.",Jama,3003749070,#87,
,CZI,2019 Novel Coronavirus—Important Information for Clinicians,10.1001/jama.2020.1490,,,,"In early December 2019 a patient was diagnosed with an unusual pneumonia in the city of Wuhan, China. By December 31 the World Health Organization (WHO) regional office in Beijing had received notification of a cluster of patients with pneumonia of unknown cause from the same city. Wuhan, the capital city of Hubei Province in central China, is the nation’s seventh largest city, with a population of 11 million people. Over the next few days, researchers at the Wuhan Institute of Virology performed metagenomics analysis using next-generation sequencing from a sample collected from a bronchoalveolar lavage and identified a novel coronavirus as the potential etiology. They called it novel coronavirus 2019 (nCoV-2019). The US Centers for Disease Control and Prevention (CDC) refers to it as 2019 novel coronavirus (2019-nCoV).",2020,"del Rio, Carlos; Malani, Preeti N.",JAMA,,#329,
,CZI,"Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China",10.1001/jama.2020.1585,,32031570,,"IMPORTANCE: In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. OBJECTIVE: To describe the epidemiological and clinical characteristics of NCIP. DESIGN, SETTING, AND PARTICIPANTS: Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. EXPOSURES: Documented NCIP. MAIN OUTCOMES AND MEASURES: Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. RESULTS: Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 109/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). CONCLUSIONS AND RELEVANCE: In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.",2020,"Wang, Dawei; Hu, Bo; Hu, Chang; Zhu, Fangfang; Liu, Xing; Zhang, Jing; Wang, Binbin; Xiang, Hui; Cheng, Zhenshun; Xiong, Yong; Zhao, Yan; Li, Yirong; Wang, Xinghuan; Peng, Zhiyong",JAMA,3005079553,#537,
,CZI,Clinical characteristics of 28 patients with novel coronavirus pneumonia,10.1001/jama.2020.1585,,,,"Objective To analysis the clinical characteristics and experiences in diagnosis and treatment of the patients with novel coronavirus pneumonia (NCP). Methods Clinical data of 28 patients with NCP in Nanning Fourth People's Hospital from January 22 to February 5 in 2020 were collected. The clinical manifestations, epidemiological history, laboratory tests, imaging examinations and treatments of patients were analyzed retrospectively. Results The 28 patients with confirmed viral pneumonia included 11 males and 17 females, ranging from 11 to 68 years. They all had history of epidemiological exposure and were all positive for 2019-nCoV nucleic acid in throat swabs. There were one mild case, 25 ordinary cases and two severe cases. There were four groups of family clusters. The illness onset ranged from 1 to 12 days after exposure, and the time from the symptom onset to the positive result of the nucleic acid test was 0 to 13 days. The clinical symptoms were mainly fever and cough, which progressed rapidly in a short period of time. Since the onset of illness, the peak values of axillary temperature of the 28 patients were 36.6~39.5 &#8451;, while five patients had no fever throughout the course of the disease with the peak temperature of &le;37 &#8451;. There were two patients presented with decreased white blood cell counts, five patients with elevated C reactive protein, six patients with abnormal alanine aminotransferase, three patients with abnormal aspartate aminotransferase,10 patients with elevated creatine kinase, three patients with elevated creatine kinase isoenzyme, four patients with elevated lactate dehydrogenase, and all with normal procalcitonin levels. The chest computed tomography examinations showed that the common features were ground glass shadows (21 cases), blurred edges (18 cases), speckles and patchy shadows (17 cases), thickening and disorder of some lung textures (7 cases), and visible band shadows (7 cases). Pulmonary lesions often progressed rapidly. One 11-year-old child was treated with alpha-interferon alone, and 27 patients were treated with alpha-interferon inhalation plus lopinavir/ritonavir with 4 withdrawal due to adverse reactions. Up to February 12, nine patients had been discharged from the hospital, who were ordinary cases, without death cases. Conclusions The NCP patients mostly present with fever and cough. Pulmonary lesions often progress rapidly. Respiratory pathogen testing should be conducted as early as possible and repeatedly. Disisolation should be cautious for suspected people who are negative for 2019-nCoV nucleic acid in pharynx swabs.",2020,"ZHAO, Rui; LIANG, Yunguang; LIN, Yanrong; LU, Ning; LI, Qiulian; LI, Youling; PAN, Pan; HE, Wei",Chinese Journal of Infectious Diseases,3005079553,#2054,
,CZI,"Manifestations of Digestive system in hospitalized patients with novel coronavirus pneumonia in Wuhan, China: a single-center, descriptive study",10.1001/jama.2020.1585,,,,"Objective To study the manifestations of digestive system of hospitalized patients with novel coronavirus pneumonia (NCP) in Wuhan, China, and to provide reference for disease control and treatment. Methods The data of hospitalized patients with NCP in the Sino-French Branch of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology was retrospectively analyzed, which included general information, nucleic acid test, severity degree of disease, incubation period, initial symptoms and manifestations of digestive system. The general information, positive rate of nucleic acid detection, and manifestations of digestive system were compared between critical patients who required non-invasive or invasive assisted ventilation (critical group) and non-critical patients without assisted ventilation (non-critical group). Continuous corrected chi-square test and independent sample median test were performed for statistical analysis. Results Among the 305 patients there were 146 males (47.9%) and 159 females (52.1%), median age 57 years old. Nucleic acid assay of nasopharynx swab or pharynx swab of 84.1% (228/271) patients were positive. Forty-six patients (15.1%) were in critical group and 259 patients (84.9%) were in non-critical group. The incubation period was one to fifteen days, and the median period was six days. The initial symptoms mainly were fever (81.1%, 163/201), cough (39.3%, 79/201), fatigue (54.7%, 110/201), and loss of appetite (50.2%, 101/201). In one to ten days after the disease onset, 79.1% (159/201) of patients developed gastrointestinal symptoms including nausea (29.4%, 59/201), vomiting (15.9%, 32/201), or abdominal pain (6.0%, 12/201). 49.5% (146/295) of patients had diarrhea, median time was 3.3 days, (3.3&plusmn;1.6) times per day, and a duration of (4.1&plusmn;2.5) days. Excluding possible drug-related diarrhea, the incidence of diarrhea still was 22.2%. Only 6.9% (4/58) of patients were found leukocytes or fecal occult blood positive in regular stool test. ALT, AST, or bilirubin increased in 39.1% (119/304) of patients at admission. Patients with ALT or AST &ge; 80 U/L only accounted for 7.9% (24/304) and 6.3% (19/304), respectively. About 2.0% (6/304) of patients also had increased bilirubin level, average level was (37.4 &plusmn; 21.1) &mu;mol/L. The median age of critical group was older than that of non-critical group (65.5 years vs. 56 years), at admission the rates of abnormal liver function test abnormal and slightly increased AST (40~80 U/L) of critical group were both higher than those of non-critical group (67.4% (31/46) vs. 34.1% (88/258) and 47.8% (22/46) vs. 21.7% (56/228)), and the differences were statistically significant ( x 2 =5.885, 18.154 and 15.723;all P &lt;0.05). There were no statistically significant differences in the proportion of male (58.7% (27/46) vs. 45.9% (119/259)), the positive rate of nucleic acid detection (94.6% (35/37) vs. 82.5% (193/234)), the percentage of patients with gastrointestinal symptoms (85.0% (17/20) vs. 78.5% (142/181)), the rate of diarrhea (44.7% (17/38)vs. 50.2% (129/257)) and ratio of patients with abnormal bilirubin level (6.5% (3/46) vs. 1.2% (3/258)) (all P &gt;0.05). Conclusions The manifestation of digestive system of hospitalized NCP patients in Wuhan is significant, the ratio of patients with diarrhea and abnormal aminotransferase level is high. And at admission the rate of patients with abnormal liver function rate of critical group is higher than that of non-critical group, which will provide reference for the prevention and treatment of NCP.",2020,"FANG, Dan; MA, Jingdong; GUAN, Jialun; WANG, Muru; SONG, Yang; TIAN, Dean; LI, Peiyuan",Chinese Journal of Digestion,3005079553,#2296,
,CZI,Analysis of clinical characteristics of new coronavirus pneumonia patients in secondary epidemic areas,10.1001/jama.2020.1585,,,,"Objective Understand the clinical characteristics of confirmed pneumonia patients infected with new corona virus in secondary epidemic areas and guide the diagnosis and treatment of novel pneumonia in secondary epidemic areas and provide a reference for clinical prevention and control of the epidemic situation. Methods The clinical data of 33 patients admitted with pneumonia caused by a novel coronavirus in the Second Affiliated Hospital of Wenzhou Medical University from January 15 to February 1, 2020, were retrospectively reviewed. At the onset of the disease, we analyzed the primary symptoms such as fever, cough, fatigue, chest tightness, chest pain and also a significant blood test results of the patients. According to the patient's contact history, it was divided into the direct infection group of the main epidemic area and the indirect contact infection group of the main epidemic areas. The difference between clinical manifestations among the two groups was analyzed. Results The main clinical symptoms of patients with novel coronavirus pneumonia in the secondary epidemic area were respiratory tract and systemic symptoms. After grouping according to the presence and absence of direct contact in the main epidemic area, there was no significant difference in baseline data between the two groups, and there was no significant difference in symptoms and signs between the two groups ( P &lt; 0.05). Some patients had serum amyloid protein (SAP) increased abnormall. Conclusions The respiratory tract and systemic symptoms are the primary symptoms of the patients with the new type of coronavirus pneumonia in the secondary epidemic area, which are not typical. The abnormal increase of serum amyloid protein (SAA) may be used as an auxiliary index for diagnosis and treatment.",2020,"JI, Weiping; CHEN, Xinxin; XU, Hui; JIN, Chenci; HU, Yunming; JI, Chengyuan; SHEN, Xian",Chinese Critical Care Medicine,3005079553,#2247,
,CZI,"Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China",10.1001/jama.2020.1623,,32031568,,,2020,"Chang, De; Lin, Minggui; Wei, Lai; Xie, Lixin; Zhu, Guangfa; Dela Cruz, Charles S.; Sharma, Lokesh",JAMA,3005347918,#538,
,CZI,Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus: Lessons From Previous Epidemics,10.1001/jama.2020.1960,,32044915,,,2020,"Swerdlow, David L.; Finelli, Lyn",JAMA,3005637261,#646,
,CZI,US Emergency Legal Responses to Novel Coronavirus: Balancing Public Health and Civil Liberties,10.1001/jama.2020.2025,,,,"With increasing numbers of cases of coronavirus disease 2019 (COVID-19) globally and in the United States, Health and Human Services (HHS) Secretary Alex Azar declared a national public health emergency on January 31. The emergency declaration of the HHS authorizes additional resources, enhanced federal powers, interjurisdictional coordination, and waivers of specific regulations. State and local public health emergency declarations are also likely. During crises, government has a special responsibility to thoughtfully balance public health protections and civil liberties.",2020,"Gostin, Lawrence O.; Hodge, James G., Jr.",JAMA,3006598047,#859,
,CZI,Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China,10.1001/jama.2020.2131,,,,"Previous studies suggest that COVID-19 is more likely to infect older adult men, particularly those with chronic comorbidities.2-4 Few infections in children have been reported. We identified all infected infants in China and described demographic, epidemiologic, and clinical features.",2020,"Wei, Min Yuan, Jingping Liu,Yu Fu,Tao Yu,Xue Zhang,Zhi-Jiang",JAMA,3006490857,#884,
,CZI,Preparing for the Most Critically Ill Patients With COVID-19: The Potential Role of Extracorporeal Membrane Oxygenation,10.1001/jama.2020.2342,,32074258,,,2020,"MacLaren, Graeme; Fisher, Dale; Brodie, Daniel",JAMA,1908342561,#1551,
,CZI,COVID-19 in Singapore—Current Experience: Critical Global Issues That Require Attention and Action,10.1001/jama.2020.2467,,,,"On December 31, 2019, China informed the World Health Organization of a novel viral pneumonia in the city of Wuhan, in Hubei Province. Singapore is an independent city-state 3400 km (2125 miles) from Wuhan, but as a major air hub had an average of 330 000 visitor arrivals from China each month in 2019. On January 2, 2020, Singapore’s Ministry of Health alerted all physicians to identify any patient with pneumonia and a recent travel history to Wuhan. On January 3, Singapore started temperature screening at its airport of all travelers arriving from Wuhan. Researchers in China identified a novel coronavirus as the causative agent on January 9, the genetic sequence was released on January 12, and human transmission to health care workers was confirmed on January 20.",2020,"Wong, John E. L.; Leo, Yee Sin; Tan, Chorh Chuan",JAMA,,#1353,
,CZI,Presumed Asymptomatic Carrier Transmission of COVID-19,10.1001/jama.2020.2565,,32083643,,,2020,"Bai, Yan; Yao, Lingsheng; Wei, Tao; Tian, Fei; Jin, Dong-Yan; Chen, Lijuan; Wang, Meiyun",JAMA,2041408682,#1696,
,CZI,Coronavirus Disease 2019 and Influenza,10.1001/jama.2020.2633,,32101254,,,2020,"Livingston, Edward; Bucher, Karen; Rekito, Andrew",Jama,3006364226,#3805,
,CZI,Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention,10.1001/jama.2020.2648,,32091533,,,2020,"Wu, Zunyou; McGoogan, Jennifer M.",JAMA,,#1741,
,CZI,Positive RT-PCR Test Results in Patients Recovered From COVID-19,10.1001/jama.2020.2783,,32105304,,,2020,"Lan, L.; Xu, D.; Ye, G.; Xia, C.; Wang, S.; Li, Y.; Xu, H.",Jama,1980645084,#2865,
,CZI,COVID-19—New Insights on a Rapidly Changing Epidemic,10.1001/jama.2020.3072,,,,"Since first reported in Wuhan, China, in late December 2019, the outbreak of the novel coronavirus now known as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has spread globally. As of February 27, 2020, more than 82 000 cases of coronavirus disease 2019 (COVID-19) (the disease caused by SARS-CoV-2) and 2800 deaths have been reported, of which approximately 95% of cases and 97% of deaths are in China. Cases have now been reported in 49 other countries. A particularly large outbreak occurred among the passengers and crew of the Diamond Princess cruise ship, where more than 700 infections are reported.",2020,"del Rio, Carlos; Malani, Preeti N.",JAMA,,#2788,
,CZI,"Response to COVID-19 in Taiwan: Big Data Analytics, New Technology, and Proactive Testing",10.1001/jama.2020.3151,,32125371,,"Taiwan is 81 miles off the coast of mainland China and was expected to have the second highest number of cases of coronavirus disease 2019 (COVID-19) due to its proximity to and number of flights between China.1 The country has 23 million citizens of which 850 000 reside in and 404 000 work in China.2,3 In 2019, 2.71 million visitors from the mainland traveled to Taiwan.4 As such, Taiwan has been on constant alert and ready to act on epidemics arising from China ever since the severe acute respiratory syndrome (SARS) epidemic in 2003. Given the continual spread of COVID-19 around the world, understanding the action items that were implemented quickly in Taiwan and assessing the effectiveness of these actions in preventing a large-scale epidemic may be instructive for other countries. COVID-19 occurred just before the Lunar New Year during which time millions of Chinese and Taiwanese were expected to travel for the holidays. Taiwan quickly mobilized and instituted specific approaches for case identification, containment, and resource allocation to protect the public health. Taiwan leveraged its national health insurance database and integrated it with its immigration and customs database to begin the creation of big data for analytics; it generated real-time alerts during a clinical visit based on travel history and clinical symptoms to aid case identification. It also used new technology, including QR code scanning and online reporting of travel history and health symptoms to classify travelers’ infectious risks based on flight origin and travel history in the past 14 days. Persons with low risk (no travel to level 3 alert areas) were sent a health declaration border pass via SMS (short message service) messaging to their phones for faster immigration clearance; those with higher risk (recent travel to level 3 alert areas) were quarantined at home and tracked through their mobile phone to ensure that they remained at home during the incubation period. Moreover, Taiwan enhanced COVID-19 case finding by proactively seeking out patients with severe respiratory symptoms (based on information from the National Health Insurance [NHI] database) who had tested negative for influenza and retested them for COVID-19; 1 was found of 113 cases. The toll-free number 1922 served as a hotline for citizens to report suspicious symptoms or cases in themselves or others; as the disease progressed, this hotline has reached full capacity, so each major city was asked to create its own hotline as an alternative. It is not known how often this hotline has been used. The government addressed the issue of disease stigma and compassion for those affected by providing food, frequent health checks, and encouragement for those under quarantine. This rapid response included hundreds of action items (eTable in the Supplement).",2020,"Wang, C. Jason; Ng, Chun Y.; Brook, Robert H.",JAMA,2157954477,#3284,
,CZI,Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore,10.1001/jama.2020.3204,,,,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China.To report the initial experience in Singapore with the epidemiologic investigation of this outbreak, clinical features, and management.Descriptive case series of the first 18 patients diagnosed with polymerase chain reaction (PCR)–confirmed SARS-CoV-2 infection at 4 hospitals in Singapore from January 23 to February 3, 2020; final follow-up date was February 25, 2020.Confirmed SARS-CoV-2 infection.Clinical, laboratory, and radiologic data were collected, including PCR cycle threshold values from nasopharyngeal swabs and viral shedding in blood, urine, and stool. Clinical course was summarized, including requirement for supplemental oxygen and intensive care and use of empirical treatment with lopinavir-ritonavir.Among the 18 hospitalized patients with PCR-confirmed SARS-CoV-2 infection (median age, 47 years; 9 [50%] women), clinical presentation was an upper respiratory tract infection in 12 (67%), and viral shedding from the nasopharynx was prolonged for 7 days or longer among 15 (83%). Six individuals (33%) required supplemental oxygen; of these, 2 required intensive care. There were no deaths. Virus was detectable in the stool (4/8 [50%]) and blood (1/12 [8%]) by PCR but not in urine. Five individuals requiring supplemental oxygen were treated with lopinavir-ritonavir. For 3 of the 5 patients, fever resolved and supplemental oxygen requirement was reduced within 3 days, whereas 2 deteriorated with progressive respiratory failure. Four of the 5 patients treated with lopinavir-ritonavir developed nausea, vomiting, and/or diarrhea, and 3 developed abnormal liver function test results.Among the first 18 patients diagnosed with SARS-CoV-2 infection in Singapore, clinical presentation was frequently a mild respiratory tract infection. Some patients required supplemental oxygen and had variable clinical outcomes following treatment with an antiretroviral agent.",2020,"Young, Barnaby Edward; Ong, Sean Wei Xiang; Kalimuddin, Shirin; Low, Jenny G.; Tan, Seow Yen; Loh, Jiashen; Ng, Oon-Tek; Marimuthu, Kalisvar; Ang, Li Wei; Mak, Tze Minn; Lau, Sok Kiang; Anderson, Danielle E.; Chan, Kian Sing; Tan, Thean Yen; Ng, Tong Yong; Cui, Lin; Said, Zubaidah; Kurupatham, Lalitha; Chen, Mark I. Cheng; Chan, Monica; Vasoo, Shawn; Wang, Lin-Fa; Tan, Boon Huan; Lin, Raymond Tzer Pin; Lee, Vernon Jian Ming; Leo, Yee-Sin; Lye, David Chien; for the Singapore Novel Coronavirus Outbreak Research, Team",JAMA,2156226164,#3256,
,CZI,"Air, Surface Environmental, and Personal Protective Equipment Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From a Symptomatic Patient",10.1001/jama.2020.3227,,,,"Coronaviruses have been implicated in nosocomial outbreaks with environmental contamination as a route of transmission. Similarly, nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported. However, the mode of transmission and extent of environmental contamination are unknown.",2020,"Ong, Sean Wei Xiang; Tan, Yian Kim; Chia, Po Ying; Lee, Tau Hong; Ng, Oon Tek; Wong, Michelle Su Yen; Marimuthu, Kalisvar",JAMA,2968894028,#3868,
,CZI,Priorities for the US Health Community Responding to COVID-19,10.1001/jama.2020.3413,,32125355,,,2020,"Adalja, Amesh A.; Toner, Eric; Inglesby, Thomas V.",JAMA,3006304371,#3467,
,CZI,"To ease anxiety over coronavirus, leaders prescribe dose of common sense",10.1002/adaw.32649,,,,Wash hands thoroughly.,2020,"Enos, Gary",Alcoholism & Drug Abuse Weekly,2052183476,#5199,
,CZI,Hematologic parameters in patients with COVID-19 infection,10.1002/ajh.25774,,32129508,,,2020,"Fan, Bingwen Eugene; Chong, Vanessa Cui Lian; Chan, Stephrene Seok Wei; Lim, Gek Hsiang; Lim, Kian Guan Eric; Tan, Guat Bee; Mucheli, Sharavan Sadasiv; Kuperan, Ponnudurai; Ong, Kiat Hoe",Am J Hematol,2600109316,#4086,
,CZI,Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV,10.1002/cbic.202000047,,,,"With the current trajectory of the 2019-nCoV outbreak unknown, public health and medicinal measures will both be needed to contain spreading of the virus and to optimize patient outcomes. Although little is known about the virus, an examination of the genome sequence shows strong homology with its better-studied cousin, SARS-CoV. The spike protein used for host cell infection shows key nonsynonymous mutations that might hamper the efficacy of previously developed therapeutics but remains a viable target for the development of biologics and macrocyclic peptides. Other key drug targets, including RNA-dependent RNA polymerase and coronavirus main proteinase (3CLpro), share a strikingly high (>95 %) homology to SARS-CoV. Herein, we suggest four potential drug candidates (an ACE2-based peptide, remdesivir, 3CLpro-1 and a novel vinylsulfone protease inhibitor) that could be used to treat patients suffering with the 2019-nCoV. We also summarize previous efforts into drugging these targets and hope to help in the development of broad-spectrum anti-coronaviral agents for future epidemics.",2020,"Morse, J. S.; Lalonde, T.; Xu, S.; Liu, W. R.",ChemBioChem,3005527412,#3842,
,CZI,News,10.1002/cind.842_3.x,,,,"Chinese scientists released genetic information on the coronavirus causing an outbreak of SARS-like illness in Wuhan, China. The Vaccine Research Institute at the US National Institutes of Health (NIH) immediately began development of a new vaccine. After the 2003 SARS outbreak, it took 20 months from the release of the viral genome to get a vaccine ready for human trials. The zika virus took six months. Now, the NIH is pushing to have a vaccine ready for testing in three to six months. The race is on. The NIH team took the template for a SARS vaccine and swapped enough code from the new virus to start a new vaccine. Researchers, having experience with SARS, already knew which part of the virus to choose for the vaccine’s antigen, a sort of red flag for the immune system. This synthetic antigen will prod the body to make antibodies.",2020,,Chemistry & Industry,2973850158,#2705,
,CZI,"Machine Learning, COVID-19 (2019-nCoV), and multi-OMICS",10.1002/cyto.a.23990,,,,"The primary plan of my editorial for this month was to highlight and comment on the special issue of this month: “Machine Learning for Single Cell Data”. I wish to emphasize and thank the Guest Editors of this special issue, Yvan Saeys and Greg Finak, for their outstanding success and hard work to assemble excellent manuscripts for this issue. I am referring to their guest editorial giving you more details on aims and scopes and elaborating on specific articles. I started drafting this editorial while attending the annual Photonics West conference in San Francisco, presumably the largest showcase on photonics technologies and instrumentation. Scientifically, the sub‐conference BIOS demonstrated the broadness and vividness of photonics technologies in life sciences and particularly in single cell analysis. When searching for relevant literature for this editorial, I was also tracking the actual global developments. This brought me to change my focus and comment on some issues that are relevant to our field and somewhat related to that of the special issue. First of all, Nature Methods announced their Method of the Year 2019 1. It is: “Single‐cell multimodal omics” and acknowledges (among others) the important contribution of highly multiplexed flow cytometry and cell sorting to the increased understanding of single cell biology and cell systems. This is motivating and confirms that cytometry is receiving the focus of attention. Concurrently, in the last weeks the relevance of the recent COVID‐19 (2019‐nCoV) outbreak and its effects started to become evident as everybody was monitoring the number of cases registered globally 2. As conference chairs, we were facing the fact that many of our speakers and colleagues became unavailable. Not only that, but the eeriness of the infection (it is transmissible already during its asymptomatic latency period of up to two weeks, recent results indicate even longer) gave many attendees an uneasy feeling. This brings me to two points worth discussing. (a) Are large scale conferences with global attendance still state of the art or should they be rethought; and (b) to what extent can cytometry support global efforts in various fields of epidemic outbreaks of infectious diseases? In the past one to two decades the world faced several outbreaks of different viral infections that were luckily not as disastrous as initially anticipated but still claimed victims. These were coronaviruses such as the Severe Acute Respiratory Syndrome coronavirus (SARS‐CoV) in 2002/2003, the Middle East Respiratory Syndrome coronavirus (MERS‐CoV) with occasional outbreaks since 2012 or influenza viruses like the H1N1 pandemic in 2009/2010. It is only a matter of time until other pandemics follow. Global travel for work and leisure supports viral spread and can transport the infection to nearly all places of the globe within days. Global conferences contribute to such a rapid spread and one should reconsider this model of scientific exchange from time to time and scrutinize potential alternatives. Models for sustainable international conferences are under testing and combine venues in close proximity to institutions with a substantial expertise on the focus area of the conference with virtual participation and contribution by internet for participants on more distant places. Although personal meetings are essential for optimal information exchange, a reduction in travel would not only reduce the risk of dissemination of disease but, as a side effect, could result in budgetary savings, reduce travel‐related emissions (in the wake of Greta), and eliminate jetlag. Now, what can Cytometry do for help in pandemics? Cytometry has already supported several achievements as a quick and non‐representative literature search shows. Image cytometry methods 3 and bead‐based flow cytometry methods 4 are at hand to enable for screening and detecting antibody virus interactions and detect viral antigens. Airway memory T‐cells and viral E protein mutations have been identified in CoV infections a potential targets for vaccine strategies 5, 6. Immune responses seem to be indicative of disease severity 6, 7 but more studies are needed to have a practical assay for decision making at hand. In fact, easy to use and rapid assays derived from Cytomics or multi‐OMICS approaches are needed to rapidly distinguish severe from mild cases and identify future critically ill individuals before symptom onset. Such a test would clearly take the pressure off of the clinicians because only those with high probability to becoming critically ill would receive intensive care early. Hopefully we will see more related studies in this journal in the near future.",2020,"Tárnok, Attila",Cytometry Part A,2949717189,#5479,
,CZI,Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics,10.1002/ddr.21656,,32129518,,"At the time of writing this commentary (February 2020), the coronavirus COVID-19 epidemic has already resulted in more fatalities compared with the SARS and MERS coronavirus epidemics combined. Therapeutics that may assist to contain its rapid spread and reduce its high mortality rates are urgently needed. Developing vaccines against the SARS-CoV-2 virus may take many months. Moreover, vaccines based on viral-encoded peptides may not be effective against future coronavirus epidemics, as virus mutations could make them futile. Indeed, new Influenza virus strains emerge every year, requiring new immunizations. A tentative suggestion based on existing therapeutics, which would likely be resistant to new coronavirus mutations, is to use available angiotensin receptor 1 (AT1R) blockers, such as losartan, as therapeutics for reducing the aggressiveness and mortality from SARS-CoV-2 virus infections. This idea is based on observations that the angiotensin-converting enzyme 2 (ACE2) very likely serves as the binding site for SARS-CoV-2, the strain implicated in the current COVID-19 epidemic, similarly to strain SARS-CoV implicated in the 2002-2003 SARS epidemic. This commentary elaborates on the idea of considering AT1R blockers as tentative treatment for SARS-CoV-2 infections, and proposes a research direction based on datamining of clinical patient records for assessing its feasibility.",2020,"Gurwitz, David",Drug Dev Res,2002765492,#4134,
,CZI,COVID-19: Lessons from SARS and MERS,10.1002/eji.202070035,,32104909,,"Within weeks of the first cases, a series of papers were released detailing the epidemiology of the disease (now termed COVID‐19) [1-3]. By early January 2020 the virus was identified and the sequence determined. The virus (termed SARS‐CoV‐2) shares 88% sequence identity to two coronaviruses found in bats, bat‐SLCoVZC45 and bat‐SL‐CoVZXC21, 79% identity with the Severe Acute Respiratory Syndrome (SARS) coronavirus and 50% identity with Middle Eastern Respiratory Syndrome (MERS) coronavirus [4]. From the first cohort of patients, 8 complete genomes were 99.9% identical in sequence. Given that the typical RNA coronavirus evolves at a rate of 104 nucleotide substitutions per year, this suggests a recent single source emergence in early December or late November 2019 [4]. SARS‐CoV‐2 is thought to be transmitted via contaminated hands, surfaces and aerosolised droplets; extensive human‐to‐human transmission is evident, with clusters of infected families and medical staff [5]. The number of confirmed cases has increased rapidly, at a rate that far outstripped the rate of rise of cases of SARS in 2002/3, raising serious global health concerns. By the 21st January, COVID‐19 cases were widespread across mainland China, soon spreading beyond the Chinese borders.",2020,"Park, Mirae; Thwaites, Ryan S.; Openshaw, Peter J. M.",European journal of immunology,2950551830,#3882,
,CZI,The indispensable role of emergency medicine in national preparedness for high consequence infectious diseases (HCIDs),10.1002/emp2.12041,,,,,2020,"Sánchez, Sarimer M.; Shenoy, Erica S.; Biddinger, Paul D.",Journal of the American College of Emergency Physicians Open,2317345803,#2556,
,CZI,Novel coronavirus pneumonia combined with viral conjunctivitis: three cases report,10.1002/hep.20111,,,,"Since January 2020, as ophthalmologists working at the center of the novel coronavirus pneumonia (NCP) outbreak in Wuhan, China, we found 3 cases in 30 NCP patients with binocular conjunctivitis. Of them, one case visited for conjunctivitis as a first symptom and then diagnosed as NCP, and two cases visited for binocular conjunctivitis during the NCP onset. In 3 patients, conjunctivitis was manifested as signs of viral conjunctivitis from mild to moderate. Their symptoms of two patients disappeared after treatment with antiviral eyedrops for 7 to 10 days and another patient died of NCP. Interestingly,although we detected positive viral nucleic acid in the conjunctiva sacs of 2 of other 27 NCP patients by using swabs and RT-PCR technology, no conjunctivitis occurred in these two patients.",2020,"YE, Ya; SONG, Yanping; YAN, Ming; HU, Cheng; CHEN, Xiao; YU, Juan; REN, Xingfeng",Chinese Journal of Experimental Ophthalmology,2090258227,#2082,
,CZI,Recent advances in the detection of respiratory virus infection in humans,10.1002/jmv.25674,,31944312,,"Respiratory tract viral infection caused by viruses or bacteria is one of the most common diseases in human worldwide, while those caused by emerging viruses, such as the novel coronavirus, 2019-nCoV that caused the pneumonia outbreak in Wuhan, China most recently, have posed great threats to global public health. Identification of the causative viral pathogens of respiratory tract viral infections is important to select an appropriate treatment, save people's lives, stop the epidemics, and avoid unnecessary use of antibiotics. Conventional diagnostic tests, such as the assays for rapid detection of antiviral antibodies or viral antigens, are widely used in many clinical laboratories. With the development of modern technologies, new diagnostic strategies, including multiplex nucleic acid amplification and microarray-based assays, are emerging. This review summarizes currently available and novel emerging diagnostic methods for the detection of common respiratory viruses, such as influenza virus, human respiratory syncytial virus (RSV), coronavirus, human adenovirus (hAdV), and human rhinovirus (hRV). Multiplex assays for simultaneous detection of multiple respiratory viruses are also described. It is anticipated that such data will assist researchers and clinicians to develop appropriate diagnostic strategies for timely and effective detection of respiratory virus infections. This article is protected by copyright. All rights reserved.",2020,"Zhang, N.; Wang, L.; Deng, X.; Liang, R.; Su, M.; He, C.; Hu, L.; Su, Y.; Ren, J.; Yu, F.; Du, L.; Jiang, S.",Journal of medical virology,2999535351,#2,
,CZI,"Emerging coronaviruses: Genome structure, replication, and pathogenesis",10.1002/jmv.25681,,,,"The recent emergence of a novel coronavirus (2019-nCoV), which is causing an outbreak of unusual viral pneumonia in patients in Wuhan, a central city in China, is another warning of the risk of CoVs posed to public health. In this minireview, we provide a brief introduction of the general features of CoVs and describe diseases caused by different CoVs in humans and animals. This review will help understand the biology and potential risk of CoVs that exist in richness in wildlife such as bats.",2020,"Chen, Y.; Liu, Q.; Guo, D.",Journal of Medical Virology,3001456238,#989,
,CZI,Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross-species transmission from snake to human,10.1002/jmv.25682,,31967321,,"The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019-nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many patients were potentially exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To determine the possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on existing sequences of the newly identified coronavirus 2019-nCoV. Results obtained from our analyses suggest that the 2019-nCoV appears to be a recombinant virus between the bat coronavirus and an origin-unknown coronavirus. The recombination occurred within the viral spike glycoprotein, which recognizes cell surface receptor. Additionally, our findings suggest that snake is the most probable wildlife animal reservoir for the 2019-nCoV based on its RSCU bias resembling snake compared to other animals. Taken together, our results suggest that homologous recombination within the spike glycoprotein may contribute to cross-species transmission from snake to humans. This article is protected by copyright. All rights reserved.",2020,"Ji, W.; Wang, W.; Zhao, X.; Zai, J.; Li, X.",Journal of medical virology,3000771439,#17,
,CZI,Global Health Concern Stirred by Emerging Viral Infections,10.1002/jmv.25683,,,,"Emerging viral infections continue to pose a major threat to global public health. In 1997, a highly pathogenic avian influenza A (H5N1) virus was found to directly spread from poultry to humans unlike previously reported transmission routs of human-to-human and livestock-to-human, stirring a grave concern for a possible influenza pandemic. This article is protected by copyright. All rights reserved.",2020,"Luo, G. G.; Gao, S. J.",Journal of medical virology,3000796089,#124,
,CZI,The 2019‐new coronavirus epidemic: Evidence for virus evolution,10.1002/jmv.25688,,,,"There is a worldwide concern about the new coronavirus 2019‐nCoV as a global public health threat. In this article, we provide a preliminary evolutionary and molecular epidemiological analysis of this new virus. A phylogenetic tree has been built using the 15 available whole genome sequences of 2019‐nCoV, 12 whole genome sequences of 2019‐nCoV, and 12 highly similar whole genome sequences available in gene bank (five from the severe acute respiratory syndrome, two from Middle East respiratory syndrome, and five from bat SARS‐like coronavirus). Fast unconstrained Bayesian approximation analysis shows that the nucleocapsid and the spike glycoprotein have some sites under positive pressure, whereas homology modeling revealed some molecular and structural differences between the viruses. The phylogenetic tree showed that 2019‐nCoV significantly clustered with bat SARS‐like coronavirus sequence isolated in 2015, whereas structural analysis revealed mutation in Spike Glycoprotein and nucleocapsid protein. From these results, the new 2019‐nCoV is distinct from SARS virus, probably trasmitted from bats after mutation conferring ability to infect humans.",2020,"Benvenuto, Domenico; Giovanetti, Marta; Ciccozzi, Alessandra; Spoto, Silvia; Angeletti, Silvia; Ciccozzi, Massimo",Journal of Medical Virology,,#2364,
,CZI,"Updated understanding of the outbreak of 2019 novel coronavirus (2019&#8208;nCoV) in Wuhan, China",10.1002/jmv.25689,,,,"To help health workers and the public recognize and deal with the 2019 novel coronavirus (2019&#8208;nCoV) quickly, effectively, and calmly with an updated understanding. A comprehensive search from Chinese and worldwide official websites and announcements was performed between 1 December 2019 and 9:30 am 26 January 2020 (Beijing time). A latest summary of 2019&#8208;nCoV and the current outbreak was drawn. Up to 24 pm, 25 January 2020, a total of 1975 cases of 2019&#8208;nCoV infection were confirmed in mainland China with a total of 56 deaths having occurred. The latest mortality was approximately 2.84% with a total of 2684 cases still suspected. The China National Health Commission reported the details of the first 17 deaths up to 24 pm, 22 January 2020. The deaths included 13 males and 4 females. The median age of the people who died was 75 (range 48&#8208;89) years. Fever (64.7%) and cough (52.9%) were the most common first symptoms among those who died. The median number of days from the occurence of the first symptom to death was 14.0 (range 6&#8208;41) days, and it tended to be shorter among people aged 70 years or more (11.5 [range 6&#8208;19] days) than those aged less than 70 years (20 [range 10&#8208;41] days; <i>P</i>&#8201;=&#8201;.033). The 2019&#8208;nCoV infection is spreading and its incidence is increasing nationwide. The first deaths occurred mostly in elderly people, among whom the disease might progress faster. The public should still be cautious in dealing with the virus and pay more attention to protecting the elderly people from the virus. <list style=""bulleted"" compact=""yes""> <listItem><br></br>The 2019&#8208;nCoV infection is spreading and its incidence is increasing nationwide. The first occurred deaths were majorly elderly people who might have faster disease progression. Although the current mortality is lower than that of the SARS&#8208;CoV and the MERS&#8208;CoV, it seems that the 2019&#8208;nCoV is very contagious. The public should still be cautious in dealing with the virus and pay more attention to protecting the elderly people from the virus.",2020,"Wang, Weier; Tang, Jianming; Wei, Fangqiang",Journal of Medical Virology,3003790823,#1264,
,CZI,Potential of large 'first generation' human-to-human transmission of 2019-nCoV,10.1002/jmv.25693,,31997390,,"To investigate the genetic diversity, time origin, and evolutionary history of the 2019-nCoV outbreak in China and Thailand, a total of 12 genome sequences of the virus with known sampling date (24 December 2019 and 13 January 2020) and geographic location (primarily Wuhan city, Hubei Province, China, but also Bangkok, Thailand) were analyzed. Phylogenetic and likelihood-mapping analyses of these genome sequences were performed. Based on our results, the star-like signal and topology of 2019-nCoV may be indicative of potentially large 'first generation' human-to-human virus transmission. We estimated that 2019-nCoV likely originated in Wuhan on 9 November 2019 (95% credible interval: 25 September 2019 and 19 December 2019), and that Wuhan is the major hub for the spread of the 2019-nCoV outbreak in China and elsewhere. Our results could be useful for designing effective prevention strategies for 2019-nCoV in China and beyond. This article is protected by copyright. All rights reserved.",2020,"Li, X.; Zai, J.; Wang, X.; Li, Y.",Journal of medical virology,3003224476,#73,
,CZI,Updates on Wuhan 2019 Novel Coronavirus Epidemic,10.1002/jmv.25695,,,,"Abstract What emerged in December 2019 as a cluster of respiratory ailments with inexplicable etiological findings in Wuhan has now claimed roughly 259 lives, sickened nearly 12 thousand more, and spread to at least 26 more nations including Hong Kong, Taiwan and Macao. This article is protected by copyright. All rights reserved.",2020,"Kofi Ayittey, Foster; Dzuvor, Christian; Kormla Ayittey, Matthew; Bennita Chiwero, Nyasha; Habib, Ahmed",Journal of Medical Virology,3005053690,#225,
,CZI,Immunoinformatics-aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019-nCoV,10.1002/jmv.25698,,,,"Abstract The 2019 novel coronavirus (2019-nCoV) outbreak has caused a large number of deaths with thousands of confirmed cases worldwide, especially in East Asia. This study took an immunoinformatics approach to identify significant cytotoxic T lymphocyte (CTL) and B cell epitopes in the 2019-nCoV surface glycoprotein. Also, interactions between identified CTL epitopes and their corresponding MHC class I supertype representatives prevalent in China were studied by molecular dynamics simulations. We identified five CTL epitopes, three sequential B cell epitopes and five discontinuous B cell epitopes in the viral surface glycoprotein. Also, during simulations, the CTL epitopes were observed to be binding MHC class I peptide-binding grooves via multiple contacts, with continuous hydrogen bonds and salt bridge anchors, indicating their potential in generating immune responses. Some of these identified epitopes can be potential candidates for development of 2019-nCoV vaccines. This article is protected by copyright. All rights reserved.",2020,"Baruah, Vargab; Bose, Sujoy",Journal of Medical Virology,3005011674,#344,
,CZI,The first two cases of 2019-nCoV in Italy: where they come from?,10.1002/jmv.25699,,,,"ABSTRACT A novel Coronavirus, 2019-nCoV, has been identified as the causal pathogen of an ongoing epidemic, with the first cases reported in Wuhan, China, last December 2019, and has since spread to other countries worldwide, included Europe and very recently Italy. In this short report, phylogenetic reconstruction was used to better understand the transmission dynamic of the virus from its first introduction in China focusing on the more recent evidence of infection in a couple of Chinese tourists arrived in Italy on 23rd January 2020 and labeled as Coronavirus Italian cases. A Maximum Clade Credibility tree has been built using a dataset of 54 genome sequences of 2019-nCoV plus 2 closely related bat strains (SARS-like CoV) available in GeneBank. Bayesian time-scaled phylogenetic analysis was implemented in BEAST 1.10.4. The Bayesian phylogenetic reconstruction showed that the 2019-2020 nCoV firstly introduced in Wuhan on the 25th November 2019, started epidemic transmission reaching many countries worldwide, including Europe and Italy where the two strains isolated dated back 19th January 2020, the same that the Chinese tourists arrived in Italy. Strains isolated outside China were intermixed with strains isolated in China as evidence of likely imported cases in Rome, Italy and Europe, as well. In conclusion, this report suggests that further spread of 2019-nCoV epidemic was supported by human mobility and that quarantine of suspected or diagnosed cases is useful to prevent further transmission. Viral genome phylogenetic analysis represents a useful tool for evaluation of transmission dynamics and preventive action. This article is protected by copyright. All rights reserved.",2020,"Giovanetti, Marta; Benvenuto, Domenico; Angeletti, Silvia; Ciccozzi, Massimo",Journal of Medical Virology,3004815273,#321,
,CZI,Genomic variance of the 2019-nCoV coronavirus,10.1002/jmv.25700,,,,"Abstract There is rising global concern for the recently emerged novel Coronavirus (2019-nCov). Full genomic sequences have been released by the worldwide scientific community in the last few weeks in order to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and SARS. We confirm high sequence similarity (>99%) between all sequenced 2019-nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019-nCoV. Despite the low heterogeneity of the 2019-nCoV genomes, we could identify at least two hyper-variable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8-encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti-coronavirus approaches. This article is protected by copyright. All rights reserved.",2020,"Ceraolo, Carmine; Giorgi, Federico M.",Journal of Medical Virology,3004499272,#421,
,CZI,Transmission dynamics and evolutionary history of 2019-nCoV,10.1002/jmv.25701,,,,"Abstract To investigate the time origin, genetic diversity, and transmission dynamics of the recent 2019-nCoV outbreak in China and beyond, a total of 32 genomes of virus strains sampled from China, Thailand, and USA with sampling dates between 24 December 2019 and 23 January 2020 were analyzed. Phylogenetic, transmission network, and likelihood-mapping analyses of the genome sequences were performed. Based on likelihood-mapping analysis, the increasing tree-like signals (from 0 to 8.2%, 18.2%, and 25.4%) over time may be indicative of increasing genetic diversity of 2019-nCoV in human hosts. We identified three phylogenetic clusters using the Bayesian inference framework and three transmission clusters using transmission network analysis, with only one cluster identified by both methods using the above genome sequences of 2019-nCoV strains. The estimated mean evolutionary rate for 2019-nCoV ranged from 1.7926 ? 10-3 to 1.8266 ? 10-3 substitutions per site per year. Based on our study, undertaking epidemiological investigations and genomic data surveillance could positively impact public health in terms of guiding prevention efforts to reduce 2019-nCOV transmission in real time. This article is protected by copyright. All rights reserved.",2020,"Li, Xingguang; Wang, Wei; Zhao, Xiaofang; Zai, Junjie; Zhao, Qiang; Li, Yi; Chaillon, Antoine",Journal of Medical Virology,3004826757,#396,
,CZI,Evolving status of the 2019 novel coronavirus Infection: proposal of conventional serologic assays for disease diagnosis and infection monitoring [Commentary/Review],10.1002/jmv.25702,,,,"Abstract The novel coronavirus (nCoV-2019) outbreak in Wuhan, China has spread rapidly nationwide, with some cases occurring in other parts of the world. Although most patients present with mild febrile illness with patchy pulmonary inflammation, a significant portion develop severe acute respiratory distress syndrome (ARDS), with a current case fatality of 2.3-3%. Diagnosis is based on clinical history and laboratory and chest radiographic findings, but confirmation currently relies on nucleic acid-based assays. The latter are playing an important role in facilitating patient isolation, treatment and assessment of infectious activities. However, due to their limited capacity to handle an epidemic of the current scale and insufficient supply of assay kits, only a portion of suspected cases can be tested, leading to incompleteness and inaccuracy in updating new cases, as well as delayed diagnosis. Furthermore, there has not been enough time to assess specificity and sensitivity. Conventional serological assays, such as enzyme-linked immunoassay (ELISA) for specific IgM and IgG antibodies, should offer a high-throughput alternative, which allows for uniform tests for all suspected patients, and can facilitate more complete identification of infected cases and avoidance of unnecessary cross infection among unselected patients. This article is protected by copyright. All rights reserved.",2020,"Xiao, Shu-Yuan; Wu, Yingjie; Liu, Huan",Journal of Medical Virology,3005036059,#529,
,CZI,The progress of 2019 Novel Coronavirus (2019-nCoV) event in China,10.1002/jmv.25705,,32048741,,"It has been more than one month since the first 2019-nCov infected person was diagnosed. However, the number of cumulative cases is keeping upward, including the severe cases and death cases. It has been proved that droplets transmission is the major route for 2019-nCov infection, and interpersonal contact could also cause the disease. Due to the fast-growing of Wuhan pneumonia and relative low cure rate, Chinese government is facing great challenges, and has taken emergency measures on disease prevention and clinical treatment, including population mobility control, building five or more hospitals for Wuhan pneumonia treatment, such as ""Huo Shen Shan"" hospital as well as developing a specific vaccine. In the meanwhile, the government shared the updated Genome Sequence of 2019-nCoV to the public, and scientists from China and oversea are working tightly and efficiently on public health emergency. This article is protected by copyright. All rights reserved.",2020,"Guan, Wang; Xian, Jin",J Med Virol,3005586597,#774,
,CZI,Economic Impacts of Wuhan 2019-nCoV on China and the World,10.1002/jmv.25706,,32048740,,"Uncertainties over the Wuhan 2019 Novel Coronavirus (2019-nCoV), which has killed 1,017 people and sickened more than 43,100 as of Feb 11,(1) has interrupted global trade and supply chains, depressed asset prices, and forced multinational businesses to make hard decisions with limited information. This article is protected by copyright. All rights reserved.",2020,"Ayittey, Foster Kofi; Ayittey, Matthew Kormla; Chiwero, Nyasha Bennita; Kamasah, Japhet Senyo; Dzuvor, Christian",J Med Virol,3005741104,#799,
,CZI,Potential Interventions for Novel Coronavirus in China: A Systemic Review,10.1002/jmv.25707,,32052466,,"An outbreak of a novel coronavirus (COVID-19 or 2019-CoV) infection has posed significant threats to international health and the economy. In the absence of treatment for this virus, there is an urgent need to find alternative methods to control the spread of disease. Here, we have conducted an online search for all treatment options related to coronavirus infections as well as some RNA virus infection and we have found that general treatments, coronavirus-specific treatments, and antiviral treatments should be useful in fighting COVID-19. We suggest that the nutritional status of each infected patient should be evaluated before the administration of general treatments and the current children's RNA virus vaccines including influenza vaccine should be immunized for uninfected people and health care workers. In addition, convalescent plasma should be given to COVID-19 patients if it is available. In conclusion, we suggest that all the potential interventions be implemented to control the emerging COVID-19 if the infection is uncontrollable. This article is protected by copyright. All rights reserved.",2020,"Zhang, Lei; Liu, Yunhui",J Med Virol,3006252254,#854,
,CZI,Does SARS-CoV-2 has a longer incubation period than SARS and MERS?,10.1002/jmv.25708,,,,"Abstract The outbreak of a novel coronavirus (SARS-CoV-2) since Dec 2019 in Wuhan, the major transportation hub in central China, became an emergency of major international concern. While several etiological studies have begun to reveal the specific biological features of this virus, the epidemic characteristics need to be elucidated. Notably, a long incubation time was reported to be associated with SARS-CoV-2 infection, leading to adjustments in screening and control policies. To avoid the risk of virus spread, all potentially exposed subjects are required to be isolated for 14 days, which is the longest predicted incubation time. However, based on our analysis of a larger dataset available so far, we find there is no observable difference between the incubation time for SARS-CoV-2, SARS and MERS, highlighting the need for larger and well annotated datasets. This article is protected by copyright. All rights reserved.",2020,"Jiang, Xuan; Rayner, Simon; Luo, Min-Hua",Journal of Medical Virology,3005802419,#857,
,CZI,"Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV",10.1002/jmv.25709,,,,"Abstract First reported from Wuhan, PR China, on 31 December 2019, the ongoing outbreak of a novel coronavirus (2019-nCoV) causes great global concerns. Based on the advice of the International Health Regulations Emergency Committee and the fact that to date 24 other countries also reported cases, the WHO Director-General declared that the outbreak of 2019-nCoV constitutes a Public Health Emergency of International Concern on 30 January 2020. Together with the other two highly pathogenic coronaviruses, the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), 2019-nCov and other yet to be identified coronaviruses pose a global threat to public health. In this mini-review, we provide a brief introduction on the pathology and pathogenesis of SARS-CoV and MERS-CoV, and extrapolate this knowledge to the newly identified 2019-nCoV. This article is protected by copyright. All rights reserved.",2020,"Liu, Jia; Zheng, Xin; Tong, Qiaoxia; Li, Wei; Wang, Baoju; Sutter, Kathrin; Trilling, Mirko; Lu, Mengji; Dittmer, Ulf; Yang, Dongliang",Journal of Medical Virology,3005949806,#856,
,CZI,The course of clinical diagnosis and treatment of a case infected with coronavirus disease 2019,10.1002/jmv.25711,,,,"Abstract A pneumonia outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first identified in Wuhan, present a major threat to public health since December 2019. There are more than 50,000 confirmed cases and 1300 dead cases worldwide for the past month or more, because of the occurrence of a highly contagious performance. Patients had clinical manifestations of fever, cough, shortness of breath, diarrhea, vomiting and so on. We herein report a case of SARS-CoV-2, describe the epidemic history, clinical diagnosis and the changes of clinical parameters during the combination therapy. This article is protected by copyright. All rights reserved.",,"Han, Wenzheng; Quan, Bin; Guo, Wei; Zhang, Jun; Lu, Yong; Feng, Gang; Wu, Qiwen; Fang, Fang; Cheng, Long; Jiao, Nanlin; Li, Xiaoning; Chen, Qing",Journal of Medical Virology,2416899403,#1304,
,CZI,Antibodies to Coronaviruses Are Higher in Older Compared with Younger Adults and Binding Antibodies Are More Sensitive than Neutralizing Antibodies in Identifying Coronavirus-Associated Illnesses,10.1002/jmv.25715,,,,"ABSTRACT Problem Human coronaviruses (HCoV) are common causes of respiratory illnesses (RI) despite pre-existing humoral immunity. Methods Sera were obtained near onset of RI and 3 to 4 weeks later as part of a prospective study of 200 subjects evaluated for RI from 2009 to 2013. Antibodies against common HCoV strains were measured by enzyme-linked immunosorbent assay (ELISA) and neutralization assay comparing older adults with cardiopulmonary diseases (99 subjects) to younger, healthy adults (101 subjects). Virus shedding was detected in respiratory secretions by polymerase chain reaction. Results Of 43 HCoV-associated illnesses, 15 (35%) occurred in 14 older adults (aged ≥ 60 years) and 28 (65%) in 28 younger adults (aged 21 to 40 years). Binding and neutralizing antibodies were higher in older adults. Only 16 (35.7%) of RI with increases in binding antibodies also had increases in neutralizing antibodies to HCoV. Increases in binding antibodies with RI were more frequent than increased neutralizing antibodies and virus shedding, and more frequent in younger compared to older adults. Conclusions Functional neutralizing antibodies were not stimulated as often as binding antibodies, explaining in part a susceptibility to reinfection with HCoV. Monitoring binding antibodies may be more sensitive for serologic detection of HCoV infections. This article is protected by copyright. All rights reserved.",,"Gorse, Geoffrey J.; Donovan, Mary M.; Patel, Gira B.",Journal of Medical Virology,2089727343,#1307,
,CZI,COVID-2019: the role of the nsp2 and nsp3 in its pathogenesis,10.1002/jmv.25719,,32083328,,"Last December 2019, a new virus, named COVID-2019 causing many cases of severe pneumonia was reported in Wuhan, China. The virus knowledge is limited and especially about COVID-2019 pathogenesis. The Open Reading Frame 1ab (ORF1ab) of COVID-2019 has been analyzed to evidence the presence of mutation caused by selective pressure on the virus. For selective pressure analysis fast-unconstrained Bayesian approximation (FUBAR) was used. Homology modelling has been performed by SwissModel and HHPred servers. The presence of transmembrane helical segments in Coronavirus ORF1ab nsp2 and nsp3, was tested by TMHMM, MEMSAT and MEMPACK tools. Three-dimensional structures have been analyzed and displayed using PyMOL. FUBAR analysis revealed the presence of potential sites under positive selective pressure (p-value < 0.05). Position 723 in the COVID-2019 has a serine instead a glycine residue, while at aminoacidic position 1010 a proline instead an isoleucine. Significant (p < 0.05) pervasive negative selection in 2416 sites (55%) was found. The positive selective pressure could account for some clinical features of this virus compared to SARS and Bat SARS-like CoV. The stabilizing mutation falling in the endosome-associated-protein-like domain of the nsp2 protein could account for COVID-2019 high ability of contagious, while the destabilizing mutation in nsp3 proteins could suggest a potential mechanism differentiating COVID-2019 from SARS. These data could be helpful for further investigation aimed to identify potential therapeutic targets or vaccine strategy, especially in the actual moment when the epidemic is ongoing and the scientific community is trying to enrich knowledge about this new viral pathogen. This article is protected by copyright. All rights reserved.",2020,"Angeletti, Silvia; Benvenuto, Domenico; Bianchi, Martina; Giovanetti, Marta; Pascarella, Stefano; Ciccozzi, Massimo",J Med Virol,3003752833,#1704,
,CZI,Facing the COVID-19 outbreak: What should we know and what could we do?,10.1002/jmv.25720,,32091134,,"A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, Hubei Province in China in December 2019 and caused a serious type of pneumonia called coronavirus disease 2019 or COVID-19. This epidemic quickly spread across China and extended to more than 20 other countries. This commentary discusses the reasons for the fast spread of SARS-CoV-2 in three aspects: the infectious sources, including the biological nature of the virus; the susceptible population; and the transmission routes. The current situations and suggestions regarding the control of the disease are summarized. This article is protected by copyright. All rights reserved.",2020,"Yang, Yi; Shang, Weilong; Rao, Xiancai",J Med Virol,3006304371,#1731,
,CZI,Combination of RT-qPCR Testing and Clinical Features For Diagnosis of COVID-19 facilitates management of SARS-CoV-2 Outbreak,10.1002/jmv.25721,,32096564,,"In December 2019, a cluster of acute respiratory illness occurred in Wuhan, Hubei Province, China. This disease is now officially known as 2019 novel coronavirus disease (COVID-19) from WHO, novel coronavirus pneumonia This article is protected by copyright. All rights reserved.",2020,"Wang, Yishan; Kang, Hanyujie; Liu, Xuefeng; Tong, Zhaohui",J Med Virol,2060528165,#1919,
,CZI,Understanding of COVID-19 based on current evidence,10.1002/jmv.25722,,32096567,,"Since December 2019, a series of unexplained pneumonia cases has been reported in Wuhan, China. On January 12, 2020, the World Health Organization (WHO) temporarily named this new virus as the 2019 novel coronavirus (2019-nCoV). On February 11, 2020, the WHO officially named the disease caused by the 2019-nCoV as Corona Virus Disease (COVID-19). The COVID-19 epidemic is spreading all over the world, especially in China. Based on the published evidence, we systematically discuss the characteristics of COVID-19 in the hope of providing a reference for future studies and help for the prevention and control of the COVID-19 epidemic. This article is protected by copyright. All rights reserved.",2020,"Sun, Pengfei; Lu, Xiaosheng; Xu, Chao; Sun, Wenjuan; Pan, Bo",J Med Virol,2513700352,#1931,
,CZI,Early Phylogenetic Estimate of the Effective Reproduction Number Of Sars-CoV-2,10.1002/jmv.25723,,32096566,,"To reconstruct the evolutionary dynamics of the 2019 novel coronavirus recently causing an outbreak in Wuhan, China, 52 SARS-CoV-2 genomes available on 04 February 2020 at GISAID were analysed. The two models used to estimate the reproduction number (coalescent-based exponential growth and a birth-death skyline method) indicated an estimated mean evolutionary rate of 7.8 x 10(-4) subs/site/year (range 1.1x10(-4) -15x10(-4) ) and a mean tMRCA of the tree root of 73 days. The estimated R value was 2.6 (range 2.1-5.1), and increased from 0.8 to 2.4 in December 2019. The estimated mean doubling time of the epidemic was between 3.6 and 4.1 days. This study proves the usefulness of phylogeny in supporting the surveillance of emerging new infections even as the epidemic is growing. This article is protected by copyright. All rights reserved.",2020,"Lai, Alessia; Bergna, Annalisa; Acciarri, Carla; Galli, Massimo; Zehender, Gianguglielmo",J Med Virol,2123665197,#1969,
,CZI,Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection,10.1002/jmv.25725,,32100876,,"OBJECTIVE: This study aimed to assess the presence of novel coronavirus in tears and conjunctival secretions of SARS-CoV-2 infected patients. METHODS: A prospective interventional case series study was performed, and 30 confirmed novel coronavirus pneumonia (NCP) patients were selected at the First Affiliated Hospital of Zhejiang University from January 26, 2020 to February 9, 2020. At an interval of 2-3 days, tear and conjunctival secretions were collected twice with disposable sampling swabs for reverse transcription polymerase chain reaction (RT-PCR) assay. RESULTS: 21 common type and 9 severe type NCP patients were enrolled. Two samples of tear and conjunctival secretions were obtained from the only one patient with conjunctivitis yielded positive RT-PCR results. 58 samples from other patents were all negative. CONCLUSION: We speculate that SARS-CoV-2 may be detected in the tears and conjunctival secretions in NCP patients with conjunctivitis. This article is protected by copyright. All rights reserved.",2020,"Xia, Jianhua; Tong, Jianping; Liu, Mengyun; Shen, Ye; Guo, Dongyu",J Med Virol,3006355661,#2115,
,CZI,Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2,10.1002/jmv.25726,,32100877,,"From the beginning of 2002 and 2012, severe respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) crossed the species barriers to infect humans caused thousands of infections and hundreds of deaths, respectively. Currently, a novel coronavirus (SARS-CoV-2) causes the outbreaks of Coronavirus Disease 2019 (COVID-19) was discovered. Until February 18, 2020, there are 72533 confirmed COVID-19 cases (including 10644 severe cases) and 1872 deaths in China. SARS-CoV-2 is surging in the public and caused substantial burdens due to its human-to-human transmission. However, the intermediate host of SARS-CoV-2 is still unclear. Finding the possible intermediate host of SARS-CoV-2 is imperative to prevent further spread of the epidemic. In this study, we used systematic comparison and analysis to predict the interaction between the receptor binding domain (RBD) of coronavirus spike protein and the host receptor, Angiotensin Converting Enzyme 2 (ACE2). The interaction between the key amino acids of S protein RBD and ACE2 indicated that like previous suggested pangolins and snacks, the turtles (C. picta bellii, C. mydas, and P. sinensis) may act as the potential intermediate hosts transmitting SARS-CoV-2 to human. This article is protected by copyright. All rights reserved.",2020,"Liu, Zhixin; Xiao, Xiao; Wei, Xiuli; Li, Jian; Yang, Jing; Tan, Huabing; Zhu, Jianyong; Zhang, Qiwei; Wu, Jianguo; Liu, Long",J Med Virol,2513547424,#2181,
,CZI,Development and Clinical Application of A Rapid IgM-IgG Combined Antibody Test for SARS-CoV-2 Infection Diagnosis,10.1002/jmv.25727,,,,"Abstract The outbreak of the novel coronavirus disease (COVID-19) quickly spread all over China and to more than 20 other countries. Although the virus (SARS-Cov-2) nucleic acid RT-PCR test has become the standard method for diagnosis of SARS-CoV-2 infection, these real-time PCR test kits have many limitations. In addition, high false negative rates were reported. There is an urgent need for an accurate and rapid test method to quickly identify large number of infected patients and asymptomatic carriers to prevent virus transmission and assure timely treatment of patients. We have developed a rapid and simple point-of-care lateral flow immunoassay which can detect IgM and IgG antibodies simultaneously against SARS-CoV-2 virus in human blood within 15 minutes which can detect patients at different infection stages. With this test kit, we carried out clinical studies to validate its clinical efficacy uses. The clinical detection sensitivity and specificity of this test were measured using blood samples collected from 397 PCR confirmed COVID-19 patients and 128 negative patients at 8 different clinical sites. The overall testing sensitivity was 88.66% and specificity was 90.63%. In addition, we evaluated clinical diagnosis results obtained from different types of venous and fingerstick blood samples. The results indicated great detection consistency among samples from fingerstick blood, serum and plasma of venous blood. The IgM-IgG combined assay has better utility and sensitivity compared with a single IgM or IgG test. It can be used for the rapid screening of SARS-CoV-2 carriers, symptomatic or asymptomatic, in hospitals, clinics, and test laboratories. This article is protected by copyright. All rights reserved.",2020,"Li, Zhengtu; Yi, Yongxiang; Luo, Xiaomei; Xiong, Nian; Liu, Yang; Li, Shaoqiang; Sun, Ruilin; Wang, Yanqun; Hu, Bicheng; Chen, Wei; Zhang, Yongchen; Wang, Jing; Huang, Baofu; Lin, Ye; Yang, Jiasheng; Cai, Wensheng; Wang, Xuefeng; Cheng, Jing; Chen, Zhiqiang; Sun, Kangjun; Pan, Weimin; Zhan, Zhifei; Chen, Liyan; Ye, Feng",Journal of Medical Virology,2940585450,#2600,
,CZI,A Systematic Review of Lopinavir Therapy for SARS Coronavirus and MERS Coronavirus–A Possible Reference for Coronavirus Disease-19 Treatment Option,10.1002/jmv.25729,,,,"Abstract In the past few decades, coronaviruses have risen as a global threat to public health. Currently, the outbreak of coronavirus disease-19 (COVID-19) from Wuhan caused a worldwide panic. There are no specific antiviral therapies for COVID-19. However, there are agents that were used during the SARS and MERS epidemics. We could learn from SARS and MERS. Lopinavir (LPV) is an effective agent that inhibits the protease activity of coronavirus. In this review, we discuss the literature on the efficacy of LPV in vitro and in vivo, especially in patients with SARS and MERS, so that we might clarify the potential for the use of LPV in patients with COVID-19. This article is protected by copyright. All rights reserved.",2020,"Yao, Tian-Tian; Qian, Jian-Dan; Zhu, Wen-Yan; Wang, Yan; Wang, Gui-Qiang",Journal of Medical Virology,,#2495,
,CZI,"Evolutionary history, potential intermediate animal host, and cross-species analyses of SARS-CoV-2",10.1002/jmv.25731,,,,"Abstract To investigate the evolutionary history of the recent outbreak of SARS-CoV-2 in China, a total of 70 genomes of virus strains from China and elsewhere with sampling dates between 24 December 2019 and 3 February 2020 were analyzed. To explore the potential intermediate animal host of the SARS-CoV-2 virus, we re-analyzed virome datasets from pangolins and representative SARS-related coronaviruses isolates from bats, with particular attention paid to the spike glycoprotein gene. We performed phylogenetic, split network, transmission network, likelihood-mapping, and comparative analyses of the genomes. Based on Bayesian time-scaled phylogenetic analysis using the tip-dating method, we estimated the time to the most recent common ancestor (TMRCA) and evolutionary rate of SARS-CoV-2, which ranged from 22?24 November 2019 and 1.19?1.31 ? 10-3 substitutions per site per year, respectively. Our results also revealed that the BetaCoV/bat/Yunnan/RaTG13/2013 virus was more similar to the SARS-CoV-2 virus than the coronavirus obtained from the two pangolin samples (SRR10168377 and SRR10168378). We also identified a unique peptide (PRRA) insertion in the human SARS-CoV-2 virus, which may be involved in the proteolytic cleavage of the spike protein by cellular proteases, and thus could impact host range and transmissibility. Interestingly, the coronavirus carried by pangolins did not have the RRAR motif. Therefore, we concluded that the human SARS-CoV-2 virus, which is responsible for the recent outbreak of COVID-19, did not come directly from pangolins. This article is protected by copyright. All rights reserved.",2020,"Li, Xingguang; Zai, Junjie; Zhao, Qiang; Nie, Qing; Li, Yi; Foley, Brian T.; Chaillon, Antoine",Journal of Medical Virology,858457542,#2602,
,CZI,Clinical trial analysis of 2019-nCoV therapy registered in China,10.1002/jmv.25733,,,,"Abstract So far, there is a lack of effective drugs for the new coronavirus pneumonia. With more and more patients diagnosed, China has carried out more than one hundred clinical studies of new coronavirus infection, including antiviral drugs, antimalarial drugs, glucocorticoids, plasma therapy, virus vaccine and other western drugs, while Chinese medicine researches accounted for half of studies. Most of the trials were initiated by investigators and the study period would last for one to eleven months. The primary endpoints included symptom improvement and virus nucleic acid turning negative, but the optimal endpoint has not been determined. Although the final results of studies will take a long time to complete, the interim research data may provide some help for the current urgent demand for drug treatment. Compared with that of during SARS period in 2003, China have the stronger capability to carry out clinical trials of new drugs in emergency period. This article is protected by copyright. All rights reserved.",2020,"Zhang, Qi; Wang, Yakun; Qi, Changsong; Shen, Lin; Li, Jian",Journal of Medical Virology,3005811358,#3022,
,CZI,Clinical characteristics of 50466 hospitalized patients with 2019-nCoV infection,10.1002/jmv.25735,,,,"Abstract Objective We aim to summarize reliable evidences of evidence-based medicine for the treatment and prevention of the 2019 novel coronavirus (2019-nCoV) by analyzing all the published studies on the clinical characteristics of patients with 2019-nCoV. Methods PubMed, Cochrane Library, Embase, and other databases were searched. Several studies on the clinical characteristics of 2019-nCoV infection were collected for Meta-analysis. Results Ten studies were included in Meta-analysis, including a total number of 50466 patients with 2019-nCoV infection. Meta-analysis shows that, among these patients, the incidence of fever was 89.1%, the incidence of cough was 72.2%, and the incidence of muscle soreness or fatigue was 42.5%. The incidence of acute respiratory distress syndrome (ARDS) was 14.8%, the incidence of abnormal chest computer tomography (CT) was 96.6%, the percentage of severe cases in all infected cases was 18.1%, and the case fatality rate of patients with 2019-nCoV infection was 4.3%. Conclusion Fever and cough are the most common symptoms in patients with 2019-nCoV infection, and most of these patients have abnormal chest CT examination. Several people have muscle soreness or fatigue as well as ARDS. Diarrhea, hemoptysis, headache, sore throat, shock, and other symptoms only occur in a small number of patients. The case fatality rate of patients with 2019-nCoV infection is lower than that of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). This article is protected by copyright. All rights reserved.",2020,"Sun, Pengfei; Qie, Shuyan; Liu, Zongjan; Ren, Jizhen; Li, Kun; Xi, Jianing",Journal of Medical Virology,2034423661,#2949,
,CZI,Development of epitope-based peptide vaccine against novel Coronavirus 2019 (SARS-COV-2): Immunoinformatics approach,10.1002/jmv.25736,,,,"ABSTRACT Recently, a novel Coronavirus (SARS-COV-2) emerged which is responsible for the recent outbreak in Wuhan, China. Genetically, it is closely related to the SARS-CoV and MERS-CoV. The situation is getting worse and worse, therefore, there is an urgent need for designing a suitable peptide vaccine component against the SARS-COV-2. Here, we characterized spike glycoprotein to obtain immunogenic epitopes. Next, we chose 13 Major Histocompatibility Complex-(MHC) I and 3 MHC-II epitopes, having antigenic properties. These epitopes are usually linked to specific linkers to build vaccine components and molecularly dock on Toll-Like Receptor (TLR)-5 to get binding affinity. Therefore, in order to provide a fast immunogenic profile of these epitopes we performed immunoinformatics analysis so that rapid development of vaccine might bring this disastrous situation to the end earlier. This article is protected by copyright. All rights reserved.",2020,"Bhattacharya, Manojit; Ranjan Sharma, Ashish; Patra, Prasanta; Ghosh, Pratik; Sharma, Garima; Chandra Patra, Bidhan; Lee, Sang-Soo; Chakraborty, Chiranjib",Journal of Medical Virology,3004614392,#2731,
,CZI,The Wuhan SARS-CoV-2 – What's Next for China,10.1002/jmv.25738,,,,"Abstract When an outbreak of pneumonia of unknown etiology occurred in Wuhan city, Hubei Province, China in December of 2019, the mystery1 was the nature of the causative agent. Because many of the patients had visited a fish and wild animal market, the possibility of a recurrence of severe acute respiratory syndrome (SARS) needed to be investigated2. Finally, could this outbreak of pneumonia be caused by a novel coronavirus that was different from those causing SARS or Middle East respiratory syndrome (MERS)3? This article is protected by copyright. All rights reserved.",2020,"Lu, Hongzhou; Stratton, Charles W.; Tang, Yi-Wei",Journal of Medical Virology,,#2894,
,CZI,Coronavirus disease (COVID-19) and neonate: What neonatologist need to know,10.1002/jmv.25740,,,,"Abstract Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) cause china epidemics with high morbidity and mortality, the infection has been transmitted to other countries. About 3 neonates and more than 230 children cases are reported. The disease condition of mainly children was mild. There is currently no evidence that SARS-CoV-2can be transmitted transplacentally from mother to the newborn. The treatment strategy for children with Coronavirus disease (COVID-19) is based on adult experience. Thus far, no deaths have been reported in the paediatric age group. This review describes the current understanding of COVID-19 infection in newborns and children. This article is protected by copyright. All rights reserved.",2020,"Lu, Qi; Shi, Yuan",Journal of Medical Virology,2604381070,#2896,
,CZI,Fecal specimen diagnosis 2019 Novel Coronavirus-Infected Pneumonia,10.1002/jmv.25742,,32124995,,"The emergence and spread of 2019 Novel Coronavirus-Infected Pneumonia (COVID-19) from Wuhan, China, it has spread globally. We extracted the data on 14 patients with laboratory-confirmed COVID-19 from Jinhua Municipal Central hospital through January 27th, 2020. We found that compared to pharyngeal swab specimens, nucleic acid detection of COVID-19 in fecal specimens was equally accurate. And we found that patients with a positive stool test did not experience gastrointestinal symptoms and had nothing to do with the severity of the lung infection. These results may help to understand the clinical diagnosis and the changes of clinical parameters of COVID-19. This article is protected by copyright. All rights reserved.",2020,"Zhang, JingCheng; Wang, SaiBin; Xue, YaDong",J Med Virol,3004824173,#3250,
,CZI,Analyzing the Epidemiological Outbreak of COVID-19: A Visual Exploratory Data Analysis (EDA) Approach,10.1002/jmv.25743,,32124990,,"There is an obvious concern globally regarding the fact about the emerging coronavirus 2019-nCoV as a worldwide public health threat. As the outbreak of COVID-19 causes by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) progresses within China and beyond, rapidly available epidemiological data are needed to guide strategies for situational awareness and intervention. The recent outbreak of pneumonia in Wuhan, China caused by the SARS-CoV-2 emphasizes the importance of analyzing the epidemiological data of this novel virus and predicting their risks of infecting people all around the globe. In this article, we present an effort to compile and analyze epidemiological outbreak information on COVID-19 based on the several open datasets on Novel Corona Virus 2019 provided by the Johns Hopkins University, World Health Organization (WHO), Chinese Center for Disease Control and Prevention (CDC), National Health Commission (NHC), and DXY. An Exploratory Data Analysis (EDA) with visualizations has been made in order to understand the number of different cases reported (confirmed, death, recovered) in different provinces of China and outside of China. Overall, at the outset of an outbreak like this, it is highly important to readily provide information in order to begin the evaluation necessary to understand the risks and begin containment activities. This article is protected by copyright. All rights reserved.",2020,"Dey, Samrat Kumar; Rahman, Md Mahbubur; Siddiqi, Umme Raihan; Howlader, Arpita",J Med Virol,2167830100,#3419,
,CZI,Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures,10.1002/jmv.25748,,,,"Abstract By Feb 27th, 2020, the outbreak of COVID-19 caused 82623 confirmed cases and 2858 deaths globally, more than Severe Acute Respiratory Syndrome (SARS) (8273 cases, 775 deaths) and Middle East Respiratory Syndrome (MERS) (1139 cases, 431 deaths) caused in 2003 and 2013 respectively. COVID-19 has spread to 46 countries internationally. Total fatality rate of COVID-19 is estimated at 3.46% by far based on published data from Chinese Center for Disease Control and Prevention (China CDC). Average incubation period of COVID-19 is around 6.4 days, ranges from 0-24 days. The basic reproductive number (R0) of COVID-19 ranges from 2-3.5 at the early phase regardless of different prediction models, which is higher than SARS and MERS. A study from China CDC showed majority of patients (80.9%) were considered asymptomatic or mild pneumonia but released large amounts of viruses at the early phase of infection, which posed enormous challenges for containing the spread of COVID-19. Nosocomial transmission was another severe problem. 3019 health workers were infected by Feb 12, 2020, which accounted for 3.83% of total number of infections, and extremely burdened the health system, especially in Wuhan. Limited epidemiological and clinical data suggest that the disease spectrum of COVID-19 may differ from SARS or MERS. We summarize latest literatures on genetic, epidemiological, and clinical features of COVID-19 in comparison to SARS and MERS and emphasize special measures on diagnosis and potential interventions. This review will improve our understanding of the unique features of COVID-19 and enhance our control measures in the future. This article is protected by copyright. All rights reserved.",2020,"Wang, Yixuan; Wang, Yuyi; Chen, Yan; Qin, Qingsong",Journal of Medical Virology,3005929298,#4416,
,CZI,The transmission and diagnosis of 2019 novel coronavirus infection disease (COVID-19): A Chinese perspective,10.1002/jmv.25749,,32141619,,"2019 novel coronavirus (SARS-CoV-2), which originated in Wuhan, China, has attracted the world's attention over the last month. The Chinese government has taken emergency measures to control the outbreak and has undertaken initial steps in the diagnosis and treatment of 2019 novel coronavirus infection disease (COVID-19). However, SARS-CoV-2 possesses powerful pathogenicity as well as transmissibility and still holds many mysteries that are yet to be solved, such as whether the virus can be transmitted by asymptomatic patients or by mothers to their infants. Our research presents selected available cases of COVID-19 in China to better understand the transmission and diagnosis regarding this infectious disease. This article is protected by copyright. All rights reserved.",2020,"Han, Y.; Yang, H.",Journal of medical virology,3005036059,#4709,
,CZI,Transmission dynamics of the COVID-19 outbreak and effectiveness of government interventions: A data-driven analysis,10.1002/jmv.25750,,32141624,,"Using the parameterized SEIR model, we simulated the spread dynamics of COVID-19 outbreak and impact of different control measures, conducted the sensitivity analysis to identify the key factor, plotted the trend curve of effective reproductive number(R) and performed data fitting after the simulation. By simulation and data fitting, the model showed the peak existing confirmed cases of 59769 arriving on 15 February 2020, with coefficient of determination close to 1 and the fitting bias 3.02%, suggesting high precision of the data fitting results. More rigorous government control policies were associated with slower increase of the infected population. Isolation and protective procedures would be less effective as more cases accrue, so the optimization of treatment plan and the development of specific drugs would be of more importance. There was an upward trend of R in the beginning, followed by a downward trend, a temporary rebound and another continuous decline. The feature of high infectiousness for sars-cov-2 led to the upward trend, and government measures contributed to the temporary rebound and declines. The declines of R could be exploited as strong evidence for the effectiveness of the interventions. Evidence from the four-phase stringent measures showed that it was significant to ensure early detection, early isolation, early treatment, adequate medical supplies, patients' being admitted to designated hospitals and comprehensive therapeutic strategy. Collaborative efforts are required to combat the novel coronavirus, focusing on both persistent strict domestic interventions and vigilance against exogenous imported cases. This article is protected by copyright. All rights reserved.",2020,"Fang, Y.; Nie, Y.; Penny, M.",Journal of medical virology,3006211350,#4665,
,CZI,Strategies suggested for emergency diagnosis and treatment of traumatic orthopedicsin the epidemic periodof Corona Virus Disease 2019,10.1002/jnr.24132,,,,"Objective To suggest strategies for emergency diagnosis and treatment of trauma orthopedics in the epidemic period of Corona Virus Disease 2019(COVID-19). Methods In the epidemic of COVID-19 from January 21 to February 15, 2020, 128 patients with orthopaedic trauma sought emergency treatment at Department of Orthopedic Surgery, The People&rsquo;s Hospital of Wuhan University. They were 71 males and 57 females with an average age of 48.7 years (from 5 to 88 years).Of them, 107 cases were treated at the outpatient department and 21 hospitalized. Emergency operations were carried out for 4 cases and selective operationsfor 17 cases. COVID-19 infections were recorded in the patients and medical staff as well. Measures taken and experiences learned were summarized since the epidemicoutbreak of COVID-19. Results Of the 107 cases treated at the outpatient department, 3 had a definite diagnosis of COVID-19 and 3 a suspected diagnosis of COVID-19. Of the 4 cases undergoing emergency surgery, one was suspected of having COVID-19. Of the 17 cases undergoing selective surgery, one was diagnosed definitely as COVID-19and 2 were suspected of COVID-19. Two nurses were diagnosed definitely as having mildCOVID-19.One doctor and one nurse were suspected of COVID-19. Since the COVID-19 infections in medical staff occurred all before the preventive and control measures for COVID-19 had been implemented,is was not ruled out that their infections might have come from communities. Conclusions It is particularly important for medical institutions of all levels to maintain safe and effective routine services while doing well in COVID-19 prevention. In the epidemic of COVID-19, front-line medical staff in emergency traumatic orthopedics is faced with great challenges in the process of diagnosing and treating patients. High-quality and safe medical services can be provided as long as nosocomial COVID-19infection is effectively controlled by rigid screening of patientsnewly admitted, classified management of inpatients, optimal management of inpatient wards, standard preventive measures in perioperative period, a perfect system for medical protection, and medical education for patients and their carers.",2020,"YANG, Yue; YU, Aixi; XIAO, Wenxia; SUN, Zhibo; LIU, Feng; WU, Fei",Chinese Journal of Orthopaedic Trauma,2747384503,#2086,
,CZI,Nursing human resource management of infectious disease hospitals under novel coronavirus pneumonia threats,10.1002/job.396,,,,"With the outbreak of novel coronavirus pneumonia, Beijing You'an Hospital has become one of the three infectious disease specialist hospitals designated to treat patients of such pneumonia. Under the premise of comprehensively implementing various emergency treatment tasks and ensuring the normal operation of other wards, the Nursing Department has put in place emergency plans and deployed due manpower for rapid response, timely personnel deployment, and reasonable reserve echelon structure. These measures have been taken as required by the patients&rsquo; numbers, critical conditions, disease diagnosis, and the guidelines of treatment and protection. While ensuring the completion of treatment work, we manage to leverage nursing human resources in a scientific, standardized and maximized efficiency manner, to ensure the quality of nursing, and the physical and mental health of nursing staff.",2020,"GUO, Huimin; ZHANG, Lili; YANG, Jiankun; BAO, Zhiying; REN, Zhen",Chinese Journal of Hospital Administration,2015808954,#2271,
,CZI,Medicinal chemistry strategies toward host targeting antiviral agents,10.1002/med.21664,,,,"Direct-acting antiviral agents (DAAs) represent a class of drugs targeting viral proteins and have been demonstrated to be very successful in combating viral infections in clinic. However, DAAs suffer from several inherent limitations, including narrow-spectrum antiviral profiles and liability to drug resistance, and hence there are still unmet needs in the treatment of viral infections. In comparison, host targeting antivirals (HTAs) target host factors for antiviral treatment. Since host proteins are probably broadly required for various viral infections, HTAs are not only perceived, but also demonstrated to exhibit broad-spectrum antiviral activities. In addition, host proteins are not under the genetic control of viral genome, and hence HTAs possess much higher genetic barrier to drug resistance as compared with DAAs. In recent years, much progress has been made to the development of HTAs with the approval of chemokine receptor type 5 antagonist maraviroc for human immunodeficiency virus treatment and more in the pipeline for other viral infections. In this review, we summarize various host proteins as antiviral targets from a medicinal chemistry prospective. Challenges and issues associated with HTAs are also discussed. Abstract Direct-acting antiviral agents (DAAs) represent a class of drugs targeting viral proteins and have been demonstrated to be very successful in combating viral infections in clinic. However, DAAs suffer from several inherent limitations, including narrow-spectrum antiviral profiles and liability to drug resistance, and hence there are still unmet needs in the treatment of viral infections. In comparison, host targeting antivirals (HTAs) target host factors for antiviral treatment. Since host proteins are probably broadly required for various viral infections, HTAs are not only perceived, but also demonstrated to exhibit broad-spectrum antiviral activities. In addition, host proteins are not under the genetic control of viral genome, and hence HTAs possess much higher genetic barrier to drug resistance as compared with DAAs. In recent years, much progress has been made to the development of HTAs with the approval of chemokine receptor type 5 antagonist maraviroc for human immunodeficiency virus treatment and more in the pipeline for other viral infections. In this review, we summarize various host proteins as antiviral targets from a medicinal chemistry prospective. Challenges and issues associated with HTAs are also discussed.",2020,"Ji, Xingyue; Li, Zhuorong",Medicinal Research Reviews,3006259301,#971,
,CZI,In Case You Haven't Heard…,10.1002/mhw.32253,,,,"China reported a major drop in new coronavirus cases to 2,641 on Feb. 15, a decline after Chinese officials began implementing measures to contain the illness, and a slight increase in new deaths to 143, Fox News reported Feb. 16. The new figures bring the total number of deaths from the virus, now known as COVID-19, to 1,523 globally, and there are 66,492 confirmed cases in the country, according to China's National Health Commission. The outbreak has taxed health care workers, doctors and nurses throughout China, particularly in Wuhan, where it first originated in December 2019. Robots have been deployed in some hospitals to deliver medicines and disinfect surfaces so workers are free to do other tasks. Survivors of the outbreak in China could face a mental health toll after weeks of being quarantined from the rest of the world, which could create anxiety and fear, according to some mental health professionals.",2020,,Mental Health Weekly,,#1710,
,CZI,Clinical and CT features in pediatric patients with COVID-19 infection: Different points from adults,10.1002/ppul.24718,,,,"Abstract Purpose To discuss the different characteristics of clinical, laboratory, and chest computed tomography (CT) in pediatric patients from adults with 2019 novel coronavirus (COVID-19) infection. Methods The clinical, laboratory, and chest CT features of 20 pediatric inpatients with COVID-19 infection confirmed by pharyngeal swab COVID-19 nucleic acid test were retrospectively analyzed during 23 January and 8 February 2020. The clinical and laboratory information was obtained from inpatient records. All the patients were undergone chest CT in our hospital. Results Thirteen pediatric patients (13/20, 65%) had an identified history of close contact with COVID-19 diagnosed family members. Fever (12/20, 60%) and cough (13/20, 65%) were the most common symptoms. For laboratory findings, procalcitonin elevation (16/20, 80%) should be pay attention to, which is not common in adults. Coinfection (8/20, 40%) is common in pediatric patients. A total of 6 patients presented with unilateral pulmonary lesions (6/20, 30%), 10 with bilateral pulmonary lesions (10/20, 50%), and 4 cases showed no abnormality on chest CT (4/20, 20%). Consolidation with surrounding halo sign was observed in 10 patients (10/20, 50%), ground-glass opacities were observed in 12 patients (12/20, 60%), fine mesh shadow was observed in 4 patients (4/20, 20%), and tiny nodules were observed in 3 patients (3/20, 15%). Conclusion Procalcitonin elevation and consolidation with surrounding halo signs were common in pediatric patients which were different from adults. It is suggested that underlying coinfection may be more common in pediatrics, and the consolidation with surrounding halo sign which is considered as a typical sign in pediatric patients.",2020,"Xia, Wei; Shao, Jianbo; Guo, Yu; Peng, Xuehua; Li, Zhen; Hu, Daoyu",Pediatric Pulmonology,2340258942,#4404,
,CZI,Novel coronavirus infection and pregnancy,10.1002/uog.22006,,,,"Clinical manifestation of COVID-19 infection during pregnancy Due to the physiological changes in their immune and cardiopulmonary systems, pregnant women are more likely to develop severe illness after infection with respiratory viruses. In 2009, pregnant women accounted for 1% of patients infected with influenza A subtype H1N1 virus, but they accounted for 5% of all H1N1-related deaths6. In addition, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), two notable strains of the coronavirus family, are both known to be responsible for severe complications during pregnancy, including the need for endotracheal intubation, admission to an intensive care unit (ICU), renal failure and death7, 8. Interestingly, the impact of COVID-19 infection on pregnant women appears to be less severe. Chen et al.9 reported the clinical characteristics of nine pregnant women with laboratory-confirmed COVID-19 in the third trimester, which comprised mainly fever and cough. Other symptoms included myalgia, malaise, sore throat, diarrhea and shortness of breath. Data from laboratory tests showed that the majority of patients had lymphopenia and increased C-reactive protein, and chest CT scans showed multiple patchy ground-glass shadows in the lungs. Pregnancy complications that appeared after the onset of COVID-19 infection included fetal distress in two of nine patients and premature rupture of the membranes in two of nine patients. None of the patients developed severe COVID-19 pneumonia or died. Another series10 of nine pregnant women with COVID-19 pneumonia presenting from mid-trimester onwards, or during the postpartum period, reported similar findings except for one woman requiring ICU care and ventilation for acute respiratory distress syndrome after the infection was diagnosed 2?days postpartum. In general, both studies reported that the clinical characteristics of the pregnant women with COVID-19 pneumonia were similar to those of non-pregnant adult patients who developed COVID-19 pneumonia2-4. These observations are also in line with what has been learned about COVID-19 pneumonia in pregnancy in several other hospitals in Wuhan, China. Pregnant healthcare professionals should follow risk-assessment and infection-control guidelines following exposure to patients with suspected or confirmed COVID-19. Adherence to recommended infection prevention and control practices is an important part of protecting all healthcare professionals in clinical settings11.",2020,"Yang, H.; Wang, C.; Poon, L. C.",Ultrasound in Obstetrics & Gynecology,3005679569,#4390,
,CZI,Histopathologic Evaluation and Scoring of Viral Lung Infection,10.1007/978-1-0716-0211-9_16,,31883098,,"Emergent coronaviruses such as MERS-CoV and SARS-CoV can cause significant morbidity and mortality in infected individuals. Lung infection is a common clinical feature and contributes to disease severity as well as viral transmission. Animal models are often required to study viral infections and therapies, especially during an initial outbreak. Histopathology studies allow for identification of lesions and affected cell types to better understand viral pathogenesis and clarify effective therapies. Use of immunostaining allows detection of presumed viral receptors and viral tropism for cells can be evaluated to correlate with lesions. In the lung, lesions and immunostaining can be qualitatively described to define the cell types, microanatomic location, and type of changes seen. These features are important and necessary, but this approach can have limitations when comparing treatment groups. Semiquantitative and quantitative tissue scores are more rigorous as these provide the ability to statistically compare groups and increase the reproducibility and rigor of the study. This review describes principles, approaches, and resources that can be useful to evaluate coronavirus lung infection, focusing on MER-CoV infection as the principal example.",2020,"Meyerholz, David K.; Beck, Amanda P.","Methods in molecular biology (Clifton, N.J.)",2996797247,#3837,
,CZI,Deducing the Crystal Structure of MERS-CoV Helicase,10.1007/978-1-0716-0211-9_6,,31883088,,"RNA virus encodes a helicase essential for viral RNA transcription and replication when the genome size is larger than 7kb. Coronavirus (CoV) has an exceptionally large RNA genome (~30kb) and it encodes an essential replicase, the nonstructural protein 13 (nsp13), a member of superfamily 1 helicases. Nsp13 is among the evolutionary most conserved proteins not only in CoVs but also in nidovirales. Thus, it is considered as an important drug target. However, the high-resolution structure of CoV nsp13 remained unavailable even until more than a decade after the outbreak of the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, which hindered the structure-based drug design. This is in part due to the intrinsic flexibility of nsp13. Here, we describe protocols of deducing the crystal structure of Middle East respiratory syndrome coronavirus (MERS-CoV) helicase in detail, which include protein expression, purification, crystallization, enzymatic characterization, and structure determination. With these methods, catalytically active recombinant MERS-CoV nsp13 protein can be prepared and crystallized and the crystal structure can be solved.",2020,"Cui, Sheng; Hao, Wei","Methods in molecular biology (Clifton, N.J.)",2997961760,#4045,
,CZI,Antigen Capture Enzyme-Linked Immunosorbent Assay for Detecting Middle East Respiratory Syndrome Coronavirus in Humans,10.1007/978-1-0716-0211-9_7,,31883089,,"The Middle East respiratory syndrome (MERS) is the second novel zoonotic disease infecting humans caused by coronavirus (CoV) in this century. To date, more than 2200 laboratory-confirmed human cases have been identified in 27 countries, and more than 800 MERS-CoV associated deaths have been reported since its outbreak in 2012. Rapid laboratory diagnosis of MERS-CoV is the key to successful containment and prevention of the spread of infection. Though the gold standard for diagnosing MERS-CoV infection in humans is still nucleic acid amplification test (NAAT) of the up-E region, an antigen capture enzyme-linked immunosorbent assay (ELISA) could also be of use for early diagnosis in less developed locations. In the present method, a step-by-step guide to perform a MERS-CoV nucleocapsid protein (NP) capture ELISA using two NP-specific monoclonal antibodies is provided for readers to develop their in-house workflow or diagnostic kit for clinical use and for mass-screening project of animals (e.g., dromedaries and bats) to better understand the spread and evolution of the virus.",2020,"Fung, J.; Lau, S. K. P.; Woo, P. C. Y.","Methods in molecular biology (Clifton, N.J.)",2997407711,#36,
,CZI,SARS-CoV-2: a potential novel etiology of fulminant myocarditis,10.1007/s00059-020-04909-z,,,,,2020,"Chen, Chen; Zhou, Yiwu; Wang, Dao Wen",Herz,,#4609,
,CZI,Critical care management of adults with community-acquired severe respiratory viral infection,10.1007/s00134-020-05943-5,,,,"With the expanding use of molecular assays, viral pathogens are increasingly recognized among critically ill adult patients with community-acquired severe respiratory illness; studies have detected respiratory viral infections (RVIs) in 17–53% of such patients. In addition, novel pathogens including zoonotic coronaviruses like the agents causing Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the 2019 novel coronavirus (2019 nCoV) are still being identified. Patients with severe RVIs requiring ICU care present typically with hypoxemic respiratory failure. Oseltamivir is the most widely used neuraminidase inhibitor for treatment of influenza; data suggest that early use is associated with reduced mortality in critically ill patients with influenza. At present, there are no antiviral therapies of proven efficacy for other severe RVIs. Several adjunctive pharmacologic interventions have been studied for their immunomodulatory effects, including macrolides, corticosteroids, cyclooxygenase-2 inhibitors, sirolimus, statins, anti-influenza immune plasma, and vitamin C, but none is recommended at present in severe RVIs. Evidence-based supportive care is the mainstay for management of severe respiratory viral infection. Non-invasive ventilation in patients with severe RVI causing acute hypoxemic respiratory failure and pneumonia is associated with a high likelihood of transition to invasive ventilation. Limited existing knowledge highlights the need for data regarding supportive care and adjunctive pharmacologic therapy that is specific for critically ill patients with severe RVI. There is a need for more pragmatic and efficient designs to test different therapeutics both individually and in combination.",2020,"Arabi, Yaseen M.; Fowler, Robert; Hayden, Frederick G.",Intensive Care Medicine,3005617185,#684,
,CZI,COVID-19: a novel coronavirus and a novel challenge for critical care,10.1007/s00134-020-05955-1,,32125458,,,2020,"Arabi, Yaseen M.; Murthy, Srinivas; Webb, Steve",Intensive Care Med,3006207556,#3461,
,CZI,How to face the novel coronavirus infection during the 2019–2020 epidemic: the experience of Sichuan Provincial People’s Hospital,10.1007/s00134-020-05964-0,,,,"January 17, 2020: the Sichuan Provincial People’s Hospital officially launched the 2019 influenza emergency response plan and established a leading group for influenza prevention and control. The president of Sichuan Provincial People’s Hospital serves as the team leader, and its members include related departments such as the administrative department, the intensive care unit, the infectious disease department, the respiratory department, nurses, the nosocomial infection control department and the radiology department. Afterwards we established multiple working groups: the emergency team, the prevention and control team, the medical emergency team, the material security team, the publicity and education team and the information updating team. Since the transmission dynamics were unclear, establishing fever clinics, isolation wards and emergency wards were the most important measures.JO - Intensive Care Medicine",2020,"Pan, Lingai; Wang, Li; Huang, Xiaobo",,,#1122,
,CZI,Intensive care during the coronavirus epidemic,10.1007/s00134-020-05966-y,,,,"As a response to the epidemic, the local government had appointed several designated hospitals for patients with SARS-CoV-2 infection. Despite a common coping strategy for mass casualty (earthquake and blast injury) in China, SARI epidemic has proposed a new challenge for healthcare workers, especially intensivists. About 15–20% of suspected and confirmed patients with SARS-CoV-2 infection in fever clinics developed severe hypoxemia (since the second week of disease course), and required some form of ventilatory support such as high-flow nasal cannula, and non-invasive and invasive mechanical ventilation. In addition, other complications might occur, including, but not limited to, shock, acute kidney injury, gastrointestinal bleeding, and rhabdomyolysis. No antiviral agents have been proven to be effective against the coronavirus. Therefore, management of critically ill patients with SARS-CoV-2 infection still remains supportive rather than definitive, indicating remarkable workload for intensive care physicians and nurses. This surge of critically ill patients in designated hospitals as well as fever clinics represents urgent demands for intensive care with regards to space, supplies, and staff (Table 1) [5,6,7,8]. Response to these demands requires cooperation between the medical rescue team, infection control specialists, local health authorities, and center for disease control and prevention [9].ER -",2020,"Qiu, Haibo; Tong, Zhaohui; Ma, Penglin; Hu, Ming; Peng, Zhiyong; Wu, Wenjuan; Du, Bin; China Critical Care Clinical Trials, Group",Intensive Care Medicine,2531638709,#1780,
,CZI,Severe SARS-CoV-2 infections: practical considerations and management strategy for intensivists,10.1007/s00134-020-05967-x,,,,"Etiological agent and epidemiology The new agent causing this pneumonia, a coronavirus (SARS-CoV-2), was identified and sequenced [3] and diagnostic tests were developed [4]. On January 30, 2020, the World Health Organization issued a worldwide public health alert on the emergence of a new epidemic viral disease. On February 3, 2020, 17,391 confirmed cases (153 cases outside of China) have been reported (https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/). The overall mortality rate of affected patients is difficult to assess at this time, because of the lack of a reliable denominator. Severe forms represent 14% of the reported cases, and the overall mortality is around 2% of the confirmed cases. To date, 153 cases have been reported in 23 countries outside China (overall, 24 cases in Europe), most of them being imported cases: tourists coming from China, or China-originating persons returning to their country of residence after traveling to visit family in Wuhan or other Chinese regions. In Europe, at least three cases in Germany and one case in France involved patients with no history of travel to China. The German case occurred after exposure to an asymptomatic contact coming from China [5].AU - Lucet, Jean-Christophe",2020,"Bouadma, Lila; Lescure, Francois-Xavier; Yazdanpanah, Yazdan; Timsit, Jean-Francois",Intensive Care Medicine,1780890786,#2356,
,CZI,"The novel coronavirus (SARS-CoV-2) infections in China: prevention, control and challenges",10.1007/s00134-020-05977-9,,,,"Since December 2019, an outbreak of novel coronavirus (SARS-CoV-2) that began from Wuhan, Hubei Province, has rapidly spread to 34 provincial-level divisions of China [1] and 25 countries around the world [2]. Up to February 15, 2020, 68,586 cases in China and 526 cases in other countries have been identified as having COVID-19 (eFigure 1). The estimated mortality rate is 3.1% in Wuhan, 2.8% in Hubei Province, 0.6% in other provinces of China, 2.4% in China and 0.4% in other countries, respectively. Faced with such a grim situation, the Chinese government has taken a series of unprecedented rigorous measures. First, all the 31 provincial-level divisions in China mainland have launched the highest level of responding mechanism for major public health emergency. Second, Wuhan and other 12 cities in Hubei Province have consecutively shut down all outbound transportation channels and suspended public transportation. Third, the State Council announced that both the Spring Festival holiday and winter vacation will be extended. Fourth, two emergency makeshift hospitals (Huoshenshan and Leishenshan hospitals) with a total capacity of 2600 beds were built and more than ten cabin hospitals were renovated with more than 10,000 beds in Wuhan. Fifth, more than 30,000 members from military and public hospitals have successively headed out to Wuhan and other cities in Hubei Province.ER -",2020,"Zhang, Sheng; Diao, Meng Yuan; Duan, Liwei; Lin, Zhaofen; Chen, Dechang",Intensive Care Medicine,3006332573,#3024,
,CZI,Challenges and countermeasures for organ donation during the SARS-CoV-2 epidemic: the experience of Sichuan Provincial People’s Hospital,10.1007/s00134-020-05978-8,,,,"Up to 09:40 February 17, 2020, there have been 70,640 confirmed SARS-CoV-2 (aka 2019-nCoV) cases in China. Sichuan Provincial People’s Hospital acts as an organ transplant center in west of China, approximately 200 solid organ transplants performed each year and can perform heart, lung, liver, kidney, small bowel, stem cell transplantation, so it is necessary to establish a hospital-specific protocol to deal with the SARS-CoV-2 infection for the donor and recipient.",2020,"Pan, Lingai; Zeng, Jie; Yang, Hongji",Intensive Care Medicine,,#1954,
,CZI,Critical care crisis and some recommendations during the COVID-19 epidemic in China,10.1007/s00134-020-05979-7,,,,"Lack of critical care resource in face of COVID-19 epidemics Based on data reported by the National Health Commission of China, there have been about 2000 new confirmed cases and?>?4000 suspected cases daily over the past week in Wuhan [3]. About 15% of the patients have developed severe pneumonia, and about 6% need noninvasive or invasive ventilatory support. Currently, there are about 1000 patients who need ventilatory support and another 120 new patients daily who require noninvasive or invasive ventilation support in Wuhan city; however, there are only about 600 ICU beds [4]. To address this shortfall, 70 ICU beds were created from general beds and the government quickly transformed three general hospitals to critical care hospitals with a total of about 2500 beds that specialize in patients with severe SARS-CoV-2 pneumonia (equipped with monitors and high-flow nasal cannula, noninvasive ventilator or invasive ventilators). An equally great (or potentially greater) problem is the shortage of trained personnel to treat these critically ill patients. Until the crisis, there were about 300 ICU physicians and 1000 ICU nurses in Wuhan city. By the end of January, more than 600 additional ICU doctors and 1500 ICU nurses were transferred to Wuhan from the rest of China. As well, an additional 3000 staff including infectious disease, respiratory, internal medicine physicians and nurses were transferred to Wuhan by the government. There are logistical issues which make care of the patients difficult. These include donning of personal protective equipment (e.g., gloves, gowns, respiratory and eye protection), lack of instruments and disposables, and shortages of supplemental oxygen. Many severe hypoxemic patients only receive high-flow nasal oxygen (HFNO) or noninvasive mechanical ventilation rather than invasive mechanical ventilation because of intubation delay or lack of mechanical ventilators (especially at early phase). Our preliminary data show that only about 25% of patients who died were intubated and received mechanical ventilation.JO - Intensive Care Medicine",2020,"Xie, Jianfeng; Tong, Zhaohui; Guan, Xiangdong; Du, Bin; Qiu, Haibo; Slutsky, Arthur S.",,2615040641,#3097,
,CZI,Clinical features and short-term outcomes of 18 patients with corona virus disease 2019 in intensive care unit,10.1007/s00134-020-05987-7,,,,,2020,"Cao, Jianlei; Hu, Xiaoyong; Cheng, Wenlin; Yu, Lei; Tu, Wen-Jun; Liu, Qiang",Intensive Care Medicine,2392835677,#3449,
,CZI,"Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China",10.1007/s00134-020-05991-x,,32125452,,,2020,"Ruan, Qiurong; Yang, Kun; Wang, Wenxia; Jiang, Lingyu; Song, Jianxin",Intensive Care Med,2997099310,#3311,
,CZI,Proposal for detection of 2019-nCoV nucleic acid in clinical laboratories,10.1007/s00246-015-1290-6,,,,"In December, the outbreak of a novel coronavirus (2019-nCoV) in Wuhan, China, has attracted extensive global attention. On January 20, 2020,the Chinese health authorities upgraded the coronavirus to a Class B infectious disease in the Law of the People's Republic of China on the Prevention and Treatment of Infectious Diseases , and considered it as Class A infectious diseases in disease control and prevention. On January 22, 2020, the 2019-nCoV nucleic acid detection test was listed as the diagnostic criteria in the 'guidelines for diagnosis and treatment of pneumonia due to 2019-nCoV (Trial Version 2)' . Therefore, standardizing the operation process of the 2019-nCoV nucleic acid detection in clinical laboratories has become a top priority. It is of paramount importance to establish standard protocols for detection of the 2019-nCoV nucleic acids in clinical laboratories to improve the reliability of the results and ensure the biosafety of laboratory personnel.",2020,"TONG, Yongqing",Chinese Journal of Laboratory Medicine,2253369457,#2145,
,CZI,Imaging features of 2019 novel coronavirus pneumonia,10.1007/s00259-020-04720-2,,,,,2020,"Xu, Xi; Yu, Chengcheng; Zhang, Lieguang; Luo, Liangping; Liu, Jinxin",European Journal of Nuclear Medicine and Molecular Imaging,3006313342,#870,
,CZI,(18)F-FDG PET/CT findings of COVID-19: a series of four highly suspected cases,10.1007/s00259-020-04734-w,,32088847,,"PURPOSE: The aim of this case series is to illustrate the (18)F-FDG PET/CT findings of patients with acute respiratory disease caused by COVID-19 in Wuhan, Hubei province of China. METHODS: We describe the (18)F-FDG PET/CT results from four patients who were admitted to the hospital with respiratory symptoms and fever between January 13 and January 20, 2020, when the COVID-19 outbreak was still unrecognized and the virus infectivity was unknown. A retrospective review of the patients' medical history, clinical and laboratory data, as well as imaging findings strongly suggested a diagnosis of COVID-19. RESULTS: All patients had peripheral ground-glass opacities and/or lung consolidations in more than two pulmonary lobes. Lung lesions were characterized by a high (18)F-FDG uptake and there was evidence of lymph node involvement. Conversely, disseminated disease was absent, a finding suggesting that COVID-19 has pulmonary tropism. CONCLUSIONS: Although (18)F-FDG PET/CT cannot be routinely used in an emergency setting and is generally not recommended for infectious diseases, our pilot data shed light on the potential clinical utility of this imaging technique in the differential diagnosis of complex cases.",2020,"Qin, Chunxia; Liu, Fang; Yen, Tzu-Chen; Lan, Xiaoli",Eur J Nucl Med Mol Imaging,2316423350,#1781,
,CZI,Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2,10.1007/s00259-020-04735-9,,,,"The pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2, also called 2019-nCoV) recently break out in Wuhan, China, and was named as COVID-19. With the spread of the disease, similar cases have also been confirmed in other regions of China. We aimed to report the imaging and clinical characteristics of these patients infected with SARS-CoV-2 in Guangzhou, China.",2020,"Xu, Xi; Yu, Chengcheng; Qu, Jing; Zhang, Lieguang; Jiang, Songfeng; Huang, Deyang; Chen, Bihua; Zhang, Zhiping; Guan, Wanhua; Ling, Zhoukun; Jiang, Rui; Hu, Tianli; Ding, Yan; Lin, Lin; Gan, Qingxin; Luo, Liangping; Tang, Xiaoping; Liu, Jinxin",European Journal of Nuclear Medicine and Molecular Imaging,3001118548,#2504,
,CZI,Standardized diagnosis and treatment of colorectal cancer during the outbreak of novel coronavirus pneumonia in Renji hospital,10.1007/s002689900293,,,,"Novel coronavirus pneumonia (NCP) is currently raging in China. It has been proven that NCP can be transmitted from human to human and cause hospital infection, which seriously threatens surgical staffs and inpatients. Although colorectal surgery is not a front-line subject in the fight against the epidemic, but in this special situation, now it is a difficult task that with the premise of how to maximize the protection for patients and their families, health of medical staff, and the safety of wards and hospitals, we can provide the highest quality medical services to ensure the orderly development of previous clinical work. Referring to the &quot;Diagnosis and Treatment Scheme for NCP (Trial Version 4 and 5)&quot; and combining the actual practice situation in our hospital with the &quot;Summary of New Coronavirus Files of Shanghai Renji Hospital&quot;, we summarize how to carry out the clinical practice of colorectal surgery under the situation of the prevention and control of the NCP epidemiology, meanwhile under such situation aiming the procedure of diagnose and treatment for emergency patients with colorectal tumor, we share the experiences of the diagnosis of colorectal tumor, the management of patients with colorectal cancer who are scheduled to be admitted for surgery, the protection of wards, the perioperative management. More importantly, we introduce in detail the operative management and perioperative management of colorectal surgery patients suspected or diagnosed with new coronary pneumonia, including prevention and control measures for medical staff, operating rooms and surgical instruments. The main points are as follows: (1) Multidisciplinary team (MDT) must be run through the diagnosis and treatment of colorectal cancer. The members include not only routine departments, but also respiratory department and infectious department. (2) Colonoscopy examination may cause cross infection of NCP to patients and doctors. Therefore, it is prior to examine the emergency cases and life-threatening patients (bleeding, obstruction, gastrointestinal foreign bodies, etc.). If the emergent patients (intestinal obstruction) with suspected or confirmed NCP, the surgeons must perform emergency surgery, and intestinal decompressive tube through colonoscopy is not recommended. (3) The colorectal cancer patients with suspected or confirmed NCP should be placed in the isolated room with separate medical devices, and the operative room with negative pressure (under-5 Pa) must be separated. All disposable medical items, body fluids and feces of the patients in perioperative periods must be unified disposed according to the medical waste standard. (4) The surgical medical workers who process colorectal cancer patients with NCP must be protected by three-level. After operation, the medical workers must receive medical observation and be isolated for 14 days. We hope our &quot;Renji experience&quot; will be beneficial to colleagues.",2020,"LUO, Yang; ZHONG, Ming",Chinese Journal of Gastrointestinal Surgery,2009124022,#1958,
,CZI,"Old Threat, New Enemy: Is Your Interventional Radiology Service Ready for the Coronavirus Disease 2019?",10.1007/s00270-020-02440-6,,32103304,,,2020,"Da Zhuang, Kun; Tan, Bien Soo; Tan, Ban Hock; Too, Chow Wei; Tay, Kiang Hiong",Cardiovascular and interventional radiology,2070556329,#4046,
,CZI,Imaging changes in patients with 2019-nCov,10.1007/s00330-020-06713-z,,,,,2020,"Pan, Yueying; Guan, Hanxiong",European Radiology,3004780338,#288,
,CZI,"Initial CT findings and temporal changes in patients with the novel coronavirus pneumonia (2019-nCoV): a study of 63 patients in Wuhan, China",10.1007/s00330-020-06731-x,,,,The purpose of this study was to observe the imaging characteristics of the novel coronavirus pneumonia.,2020,"Pan, Yueying; Guan, Hanxiong; Zhou, Shuchang; Wang, Yujin; Li, Qian; Zhu, Tingting; Hu, Qiongjie; Xia, Liming",European Radiology,3006354146,#869,
,CZI,Outbreak of novel coronavirus (COVID-19): What is the role of radiologists?,10.1007/s00330-020-06748-2,,,,• Novel coronavirus (COVID-19)-infected pneumonia usually manifests as bilateral ground-glass opacities in the lung periphery on chest CT scans.,2020,"Kim, Hyungjin",European Radiology,3005943294,#1223,
,CZI,The 2019 novel cornoavirus pneumonia with onset of oculomotor nerve palsy: a case study,10.1007/s00415-020-09773-9,,,,"On December 31, 2019, several cases of pneumonia of unknown etiology have been reported in Wuhan, Hubei province, China [1,2,3]. On January 7, 2020, Chinese health authorities confirmed that these cases were associated with a novel coronavirus, which was subsequently named 2019­nCoV by WHO [4]. Previous study [5] reported that virus infection can cause several neurological complications, including polyneuritis, Guillain–Barre syndrome (GBS), meningitis, encephalomyelitis, and encephalopathy. We describe a rare case of 2019-CoV infection and acute unilateral isolated oculomotor nerve palsy. In this case, the diagnosis was made based on the chest computed CT manifestations and throat swab sample test. A 62-year-old man was admitted to our department with a 5-day history of persistent diplopia and a droopy left eyelid. During initial hospital assessment, he endorsed limb weakness and poor spirit. He denied any fever, neck stiffness, headache, cough, shortness of breath, chest pain, or photophobia. He had a history of alcohol and tobacco use, type II diabetes mellitus and hypertension (both well controlled by drugs), and lacunar infarction (without sequela).DA - 2020/02/25",2020,"Wei, Heng; Yin, Hongxiang; Huang, Min; Guo, Zhenli",Journal of Neurology,2758126530,#1918,
,CZI,Stepping up infection control measures in ophthalmology during the novel coronavirus outbreak: an experience from Hong Kong,10.1007/s00417-020-04641-8,,,,Coronavirus disease (COVID-19) has rapidly emerged as a global health threat. The purpose of this article is to share our local experience of stepping up infection control measures in ophthalmology to minimise COVID-19 infection of both healthcare workers and patients.,2020,"Lai, Tracy H. T.; Tang, Emily W. H.; Chau, Sandy K. Y.; Fung, Kitty S. C.; Li, Kenneth K. W.",Graefe's Archive for Clinical and Experimental Ophthalmology,3004790666,#3156,
,CZI,Development of an indirect ELISA for detecting porcine deltacoronavirus IgA antibodies,10.1007/s00705-020-04541-6,,32052195,,"Porcine deltacoronavirus (PDCoV) is a novel coronavirus that can cause vomiting and watery diarrhea in pigs and death in piglets. Since PDCoV was first detected in 2009 in Hong Kong, the prevalence of PDCoV has increased in recent years, resulting in serious economic losses to the swine industry. The coronavirus spike (S) protein is an antigen that has been demonstrated to contain epitopes that induce neutralizing antibodies. The presence of serum and milk IgA antibodies against pathogens that replicate primarily on mucosal surfaces is important for mucosal immunity. Here, an indirect anti-PDCoV IgA antibody enzyme-linked immunosorbent assay (PDCoV S1 IgA ELISA) using the purified S1 portion of S protein as the coating antigen was developed to detect PDCoV IgA antibodies in serum and sow's milk. A receiver operating characteristic (ROC) curve analysis showed high specificity and sensitivity of the PDCoV-S1-IgA-ELISA based on samples confirmed by IFA. Anti-PDCoV IgA antibodies in 152 serum samples and 65 milk samples collected from six farms that had experienced diarrhea outbreaks within previous last two years were detected by this assay, and 62.5% of the serum samples and 100% of the milk samples were positive for PDCoV. The indirect ELISA method established in this study will provide a convenient tool for measurement of serum and milk IgA levels against PDCoV in pig herds, rapid detection of PDCoV infection in pigs, and evaluation of the immunogenicity of vaccines.",2020,"Lu, Manman; Liu, Qiuge; Wang, Xiaobo; Zhang, Jialin; Zhang, Xin; Shi, Da; Liu, Jianbo; Shi, Hongyan; Chen, Jianfei; Feng, Li",Arch Virol,3006146227,#877,
,CZI,Coronavirus COVID-19 impacts to dentistry and potential salivary diagnosis,10.1007/s00784-020-03248-x,,32078048,,,2020,"Sabino-Silva, Robinson; Jardim, Ana Carolina Gomes; Siqueira, Walter L.",Clin Oral Investig,2141065236,#1504,
,CZI,"Public awareness of coronavirus in Al-Jouf region, Saudi Arabia",10.1007/s10389-020-01209-y,,,,"Since 2012 and to date, outbreak/new cases of Middle East respiratory syndrome-related coronavirus (MERS-CoV) were always reported in Saudi Arabia. Al-Jouf region is considered as one of the most vulnerable areas to the disease outbreak. This research aimed to assess (to the best of our knowledge), for the first time, the current level of awareness towards MERS-CoV among the Al-Jouf region population through a well-designed multistage questionnaire.",2020,"Nooh, Hanaa Zakaria; Alshammary, Rawan Humaidy; Alenezy, Jomanh Mohammed; Alrowaili, Njood Hial; Alsharari, Amani Jaded; Alenzi, Njood Menwer; Sabaa, Hanan E.",Journal of Public Health,3006484532,#1794,
,CZI,Containing 2019-nCoV (Wuhan) coronavirus,10.1007/s10729-020-09504-6,,,,"The novel coronavirus 2019-nCoV first appeared in December 2019 in Wuhan, China. While most of the initial cases were linked to the Huanan Seafood Wholesale Market, person-to-person transmission has been verified. Given that a vaccine cannot be developed and deployed for at least a year, preventing further transmission relies upon standard principles of containment, two of which are the isolation of known cases and the quarantine of persons believed at high risk of exposure. This note presents probability models for assessing the effectiveness of case isolation and quarantine within a community during the initial phase of an outbreak with illustrations based on early observations from Wuhan.",2020,"Kaplan, Edward H.",Health Care Management Science,3004824173,#4764,
,CZI,The Role of Augmented Intelligence (AI) in Detecting and Preventing the Spread of Novel Coronavirus,10.1007/s10916-020-1536-6,,,,"The 2019-nCov will not be the last epidemic to challenge public health experts. The growth of AI-driven techniques to identify epidemiologic risks early will be key to our improvement of prediction, prevention, and detection of future global health risks. The devastating situation in Wuhan, China and future epidemics will also find value in ongoing research in 2019-nCov case detection, spread prediction, treatment effectiveness, and containment. The wide variety, velocity, and veracity of data now available in crises yield data sets that many researchers will now need to incorporate into evermore complex models. This requires expansion of talent within AI for healthcare applications. AI is no longer a niche research area nor is it a tool for the most advanced healthcare systems only, its global impact on healthcare is real and its potential to save lives in this epidemic as well as future epidemics should not be underestimated. It is critical to the global health of all humankind for the scientific community to embrace AI and leverage its power in securing our collective future.ER -",2020,"Long, Justin B.; Ehrenfeld, Jesse M.",Journal of Medical Systems,3005084260,#299,
,CZI,Antivirals in medical biodefense,10.1007/s11262-020-01737-5,,,,"The viruses historically implicated or currently considered as candidates for misuse in bioterrorist events are poxviruses, filoviruses, bunyaviruses, orthomyxoviruses, paramyxoviruses and a number of arboviruses causing encephalitis, including alpha- and flaviviruses. All these viruses are of concern for public health services when they occur in natural outbreaks or emerge in unvaccinated populations. Recent events and intelligence reports point to a growing risk of dangerous biological agents being used for nefarious purposes. Public health responses effective in natural outbreaks of infectious disease may not be sufficient to deal with the severe consequences of a deliberate release of such agents. One important aspect of countermeasures against viral biothreat agents are the antiviral treatment options available for use in post-exposure prophylaxis. These issues were adressed by the organizers of the 16th Medical Biodefense Conference, held in Munich in 2018, in a special session on the development of drugs to treat infections with viruses currently perceived as a threat to societies or associated with a potential for misuse as biothreat agents. This review will outline the state-of-the-art methods in antivirals research discussed and provide an overview of antiviral compounds in the pipeline that are already approved for use or still under development.",2020,"Bugert, J. J.; Hucke, F.; Zanetta, P.; Bassetto, M.; Brancale, A.",Virus Genes,2728328470,#1327,
,CZI,Physikalischer Schutz vor respiratorischen Viren,10.1007/s11298-020-7917-9,,,,"Durch die Bildung eines Films auf den Zellen der Nasenschleimhaut kann ein Spray dabei helfen, sich vor Erkältungsviren zu schützen. Der aus Rotalgen gewonnene Wirkstoff Carragelose bildet eine physikalische Barriere auf der Nasenschleimhaut, in der sich respiratorische Viren - darunter auch humane Coronaviren - verfangen. So wird der Kontakt zwischen ihnen und menschlichen Zellen weitestgehend unterbunden und der weitere Infektionsweg deutlich erschwert. In klinischen Studien an Patienten mit viral bedingten grippalen Infekten konnte gezeigt werden, dass Carragelose-haltige Sprays zur Anwendung in der Nase (wie algovir Effekt) die Viruslast nach drei bis vier Behandlungstagen um mehr als 90% reduzieren können. Getestet wurde die Wirksamkeit des Wirkstoffs unter anderem an verschiedenen Typen humaner Coronaviren - jedoch nicht an dem Coronavirus SARS-CoV-2. Daher können derzeit keine endgültigen Rückschlüsse zur Aktivität und Effektivität des Wirkstoffs gegen 2SARS-CoV-2 gezogen werden. Allerdings haben Carragelose-Erkältungssprays ein ausgezeichnetes Sicherheitsprofil, weshalb sie durchaus ergänzend zu den gängigen Maßnahmen zum Schutz vor respiratorischen Viren wie Händedesinfektion und Mundschutz angewendet und den Apothekenkunden empfohlen werden können. AU - API, Redaktion",2020,,CME,2168055967,#3470,
,CZI,Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission,10.1007/s11427-020-1637-5,,32009228,,,2020,"Xu, Xintian; Chen, Ping; Wang, Jingfang; Feng, Jiannan; Zhou, Hui; Li, Xuan; Zhong, Wu; Hao, Pei",Sci China Life Sci,2999364275,#253,
,CZI,Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury,10.1007/s11427-020-1643-8,,,,"The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.",2020,"Liu, Yingxia; Yang, Yang; Zhang, Cong; Huang, Fengming; Wang, Fuxiang; Yuan, Jing; Wang, Zhaoqin; Li, Jinxiu; Li, Jianming; Feng, Cheng; Zhang, Zheng; Wang, Lifei; Peng, Ling; Chen, Li; Qin, Yuhao; Zhao, Dandan; Tan, Shuguang; Yin, Lu; Xu, Jun; Zhou, Congzhao; Jiang, Chengyu; Liu, Lei",Science China Life Sciences,3005655936,#693,
,CZI,Bat origin of a new human coronavirus: there and back again,10.1007/s11427-020-1645-7,,,,,2020,"Li, Xiang; Song, Yuhe; Wong, Gary; Cui, Jie",Science China Life Sciences,3006649197,#697,
,CZI,Clinical trials for the treatment of Coronavirus disease 2019 (COVID-19): A rapid response to urgent need,10.1007/s11427-020-1660-2,,,,"Clinical trial for COVID-19 was first registered on January 23, 2020. In the last few weeks, an escalating number of clinical trials has been planned and registered with ongoing investigations taking place. From the Chinese Clinical Trial Registry (http://www.chictr.org.cn) and U.S. National Library of Medicine Clinical Trial Registry (https://clinicaltrials. gov), there are 125 clinical trials registered by February 18, 2020, focusing on the treatment of COVID-19. There is an upward trend on the number of registered clinical trials (Figure 1). Among the 125 clinical trials on treatment, 33.3% used anti-viral agents, 14.7% anti-inflammation or immunomodulators, 33.3% herbs or traditional Chinese medicine (TCM), 9.3% cell-based therapy, 2.3% antioxidation and 7.0% other approaches. Pharmaceutical companies, government, institutions, physicians and scientists are the main force behind these researches. 17 years ago (2003), SARS affectedAU - Zhang, Tengyue",2020,"He, Yudi; Xu, Wenshuai; Ma, Aiping; Yang, Yanli; Xu, Kai-Feng",Science China Life Sciences,3006394629,#3246,
,CZI,Review of the Clinical Characteristics of Coronavirus Disease 2019 (COVID-19),10.1007/s11606-020-05762-w,,,,"In late December 2019, a cluster of cases with 2019 Novel Coronavirus pneumonia (SARS-CoV-2) in Wuhan, China, aroused worldwide concern. Previous studies have reported epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19). The purpose of this brief review is to summarize those published studies as of late February 2020 on the clinical features, symptoms, complications, and treatments of COVID-19 and help provide guidance for frontline medical staff in the clinical management of this outbreak.",2020,"Jiang, Fang; Deng, Liehua; Zhang, Liangqing; Cai, Yin; Cheung, Chi Wai; Xia, Zhengyuan",Journal of General Internal Medicine,2604381070,#4546,
,CZI,"Can Chinese Medicine Be Used for Prevention of Corona Virus Disease 2019 (COVID-19)? A Review of Historical Classics, Research Evidence and Current Prevention Programs",10.1007/s11655-020-3192-6,,32065348,,"OBJECTIVE: Since December 2019, an outbreak of corona virus disease 2019 (COVID-19) occurred in Wuhan, and rapidly spread to almost all parts of China. This was followed by prevention programs recommending Chinese medicine (CM) for the prevention. In order to provide evidence for CM recommendations, we reviewed ancient classics and human studies. METHODS: Historical records on prevention and treatment of infections in CM classics, clinical evidence of CM on the prevention of severe acute respiratory syndrome (SARS) and H1N1 influenza, and CM prevention programs issued by health authorities in China since the COVID-19 outbreak were retrieved from different databases and websites till 12 February, 2020. Research evidence included data from clinical trials, cohort or other population studies using CM for preventing contagious respiratory virus diseases. RESULTS: The use of CM to prevent epidemics of infectious diseases was traced back to ancient Chinese practice cited in Huangdi's Internal Classic (Huang Di Nei Jing) where preventive effects were recorded. There were 3 studies using CM for prevention of SARS and 4 studies for H1N1 influenza. None of the participants who took CM contracted SARS in the 3 studies. The infection rate of H1N1 influenza in the CM group was significantly lower than the non-CM group (relative risk 0.36, 95% confidence interval 0.24-0.52; n=4). For prevention of COVID-19, 23 provinces in China issued CM programs. The main principles of CM use were to tonify qi to protect from external pathogens, disperse wind and discharge heat, and resolve dampness. The most frequently used herbs included Radix astragali (Huangqi), Radix glycyrrhizae (Gancao), Radix saposhnikoviae (Fangfeng), Rhizoma Atractylodis Macrocephalae (Baizhu), Lonicerae Japonicae Flos (Jinyinhua), and Fructus forsythia (Lianqiao). CONCLUSIONS: Based on historical records and human evidence of SARS and H1N1 influenza prevention, Chinese herbal formula could be an alternative approach for prevention of COVID-19 in high-risk population. Prospective, rigorous population studies are warranted to confirm the potential preventive effect of CM.",2020,"Luo, Hui; Tang, Qiao-Ling; Shang, Ya-Xi; Liang, Shi-Bing; Yang, Ming; Robinson, Nicola; Liu, Jian-Ping",Chin J Integr Med,3006394629,#1125,
,CZI,Prevention and consideration for the biosafety of laboratory testing under epidemic condition,10.1007/s12072-016-9736-3,,,,"Laboratory testing plays an important role in the diagnosis and treatment of patients with Novel Coronavirus pneumonia. However, the lack of understanding of the virus in the early stage led to great difficulties in biosafety protection for clinical laboratories. Based on the latest researches and findings about the virus, this paper provides some personal opinions on the biosafety prevention in clinical laboratorians under epidemic condition for the reference of laboratory workers.",2020,"YE, Qing; LI, Wei; ZHOU, Mingming; FU, Junfen; SHU, Qiang; GONG, Fangqi; SHANG, Shiqiang",Chinese Journal of Laboratory Medicine,2402472675,#2083,
,CZI,Clinical Features and Treatment of 2019-nCov Pneumonia Patients in Wuhan: Report of A Couple Cases,10.1007/s12250-020-00203-8,,,,"The two patients were a couple. The male was 38 years old, and was admitted to the hospital due to fever for one week and dyspnea for one day on Dec. 27, 2019. On admission, he had slight cough of a little green viscous sputum. He had been treated with normal anti-infective therapy in another hospital for 3 days, but did not respond it. After then, he visited our department. The radiography of the chest at the OPD suggested the right lung infection.ER -",2020,"Zhang, Zhan; Li, Xiaochen; Zhang, Wei; Shi, Zheng-Li; Zheng, Zhishui; Wang, Tao",Virologica Sinica,3004978148,#484,
,CZI,Old Weapon for New Enemy: Drug Repurposing for Treatment of Newly Emerging Viral Diseases,10.1007/s12250-020-00204-7,,,,"In a very recent work by a research team led by Drs. Gengfu Xiao, Wu Zhong and Zhihong Hu, the antiviral efficiency of the FDA-approved drugs including ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine (CQ) and two well-known broad-spectrum antiviral drugs remdesivir (RDV, GS-5734) and favipiravir (T-705) were evaluated against a clinical isolate of 2019-nCoV in a cell culture infection model (Wang et al.2020). The authors found that two compounds CQ (EC50 value?=?1.13 µmol/L; CC50?>?100 µmol/L, SI?>?88.50) and RDV (EC50?=?0.77 µmol/L; CC50?>?100 µmol/L; SI?>?129.87) potently blocked virus infection at low-micromolar concentration and showed high selectivity index (SI). From the in vitro results, these two compounds appear promising to be transformed into clinical drugs for treatment of 2019-nCoV infections.AU - Guo, Deyin",2020,,Virologica Sinica,3006339206,#651,
,CZI,Compensation of ACE2 Function for Possible Clinical Management of 2019-nCoV-Induced Acute Lung Injury,10.1007/s12250-020-00205-6,,32034638,,,2020,"Wu, Yuntao",Virol Sin,3004883038,#485,
,CZI,The First Disease X is Caused by a Highly Transmissible Acute Respiratory Syndrome Coronavirus,10.1007/s12250-020-00206-5,,,,"Based on the announcement of the World Health Organization (WHO) in 2018, the Wuhan pneumonia caused by an unknown etiology should be recognized as the first Disease X. Later, the pathogen was identified to be a novel coronavirus denoted 2019-nCoV, which has 79.5% and 96% whole genome sequence identify to SARS-CoV and bat SARS-related coronavirus (SARSr-CoV-RaTG13), respectively, suggesting its potential bat origin. With high human-to-human transmission rate (R0), 2019-nCoV has quickly spread in China and other countries, resulting in 34,953 confirmed cases and 725 deaths as of 8 February 2020, thus calling for urgent development of therapeutics and prophylactics. Here we suggest renaming 2019-nCoV as “transmissible acute respiratory syndrome coronavirus (TARS-CoV)” and briefly review the advancement of research and development of neutralizing antibodies and vaccines targeting the receptor-binding domain (RBD) and viral fusion inhibitors targeting the heptad repeat 1 (HR1) domain in spike protein of 2019-nCoV.",2020,"Jiang, Shibo; Shi, Zheng-Li",Virologica Sinica,3006422522,#969,
,CZI,Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools,10.1007/s12250-020-00207-4,,32125642,,"Currently there is no effective antiviral therapy for SARS-CoV-2 infection, which frequently leads to fatal inflammatory responses and acute lung injury. Here, we discuss the various mechanisms of SARS-CoV-mediated inflammation. We also assume that SARS-CoV-2 likely shares similar inflammatory responses. Potential therapeutic tools to reduce SARS-CoV-2-induced inflammatory responses include various methods to block FcR activation. In the absence of a proven clinical FcR blocker, the use of intravenous immunoglobulin to block FcR activation may be a viable option for the urgent treatment of pulmonary inflammation to prevent severe lung injury. Such treatment may also be combined with systemic anti-inflammatory drugs or corticosteroids. However, these strategies, as proposed here, remain to be clinically tested for effectiveness.",2020,"Fu, Yajing; Cheng, Yuanxiong; Wu, Yuntao",Virol Sin,3006390878,#3407,
,CZI,The Risk and Prevention of Novel Coronavirus Pneumonia Infections Among Inpatients in Psychiatric Hospitals,10.1007/s12264-020-00476-9,,,,"Since the middle of December 2019, human-to-human transmission of novel coronavirus pneumonia (NCP, also called COVID-19) has occurred among close contacts [1]. After the outbreak on January 21, 2020, it was swiftly included among the Class B infectious diseases stipulated in the Law of the People’s Republic of China on the Prevention and Control of Infectious Diseases, and measures for prevention and control of Class A infectious diseases were adopted. At 21:27 on February 12, 2020, the China News Network updated information to include epidemic data from the National Health Commission and official channels in Hong Kong, Macao, and Taiwan regions: the highest death rate was in Wuhan City (Table 1). Overload of inpatients at hospitals may play a negative role in the overall therapeutic effect and contribute to the death rateER -",2020,"Zhu, Yuncheng; Chen, Liangliang; Ji, Haifeng; Xi, Maomao; Fang, Yiru; Li, Yi",Neuroscience Bulletin,2006683952,#1720,
,CZI,A numerical study of ventilation strategies for infection risk mitigation in general inpatient wards,10.1007/s12273-020-0623-4,,,,"Aerial dispersion of human exhaled microbial contaminants and subsequent contamination of surfaces is a potential route for infection transmission in hospitals. Most general hospital wards have ventilation systems that drive air and thus contaminants from the patient areas towards the corridors. This study investigates the transport mechanism and deposition patterns of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) within a typical six bedded general inpatient ward cubicle through numerical simulation. It demonstrates that both air change and exhaust airflow rates have significant effects on not only the airflow but also the particle distribution within a mechanically ventilated space. Moreover, the location of an infected patient within the ward cubicle is crucial in determining the extent of infection risk to other ward occupants. Hence, it is recommended to provide exhaust grilles in close proximity to a patient, preferably above each patient’s bed. To achieve infection prevention and control, high exhaust airflow rate is also suggested. Regardless of the ventilation design, all patients and any surfaces within a ward cubicle should be regularly and thoroughly cleaned and disinfected to remove microbial contamination. The outcome of this study can serve as a source of reference for hospital management to better ventilation design strategies for mitigating the risk of infection.",2020,"Satheesan, Manoj Kumar; Mui, Kwok Wai; Wong, Ling Tim",Building Simulation,2886620552,#1937,
,CZI,"Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts' consensus statement",10.1007/s12519-020-00343-7,,32034659,,"Since the outbreak of 2019 novel coronavirus infection (2019-nCoV) in Wuhan City, China, by January 30, 2020, a total of 9692 confirmed cases and 15,238 suspected cases have been reported around 31 provinces or cities in China. Among the confirmed cases, 1527 were severe cases, 171 had recovered and been discharged at home, and 213 died. And among these cases, a total of 28 children aged from 1 month to 17 years have been reported in China. For standardizing prevention and management of 2019-nCoV infections in children, we called up an experts' committee to formulate this experts' consensus statement. This statement is based on the Novel Coronavirus Infection Pneumonia Diagnosis and Treatment Standards (the fourth edition) (National Health Committee) and other previous diagnosis and treatment strategies for pediatric virus infections. The present consensus statement summarizes current strategies on diagnosis, treatment, and prevention of 2019-nCoV infection in children.",2020,"Shen, Kunling; Yang, Yonghong; Wang, Tianyou; Zhao, Dongchi; Jiang, Yi; Jin, Runming; Zheng, Yuejie; Xu, Baoping; Xie, Zhengde; Lin, Likai; Shang, Yunxiao; Lu, Xiaoxia; Shu, Sainan; Bai, Yan; Deng, Jikui; Lu, Min; Ye, Leping; Wang, Xuefeng; Wang, Yongyan; Gao, Liwei; China National Clinical Research Center for Respiratory, Diseases; National Center for Children’s Health, Beijing China; Group of Respirology, Chinese Pediatric Society Chinese Medical Association; Chinese Medical Doctor Association Committee on Respirology, Pediatrics; China Medicine Education Association Committee on, Pediatrics; Chinese Research Hospital Association Committee on, Pediatrics; Chinese Non-government Medical Institutions Association Committee on, Pediatrics; China Association of Traditional Chinese Medicine, Committee on Children’s Health; Medicine, Research; China News of Drug Information Association, Committee on Children’s Safety Medication; Global Pediatric Pulmonology, Alliance",World J Pediatr,3004896587,#482,
,CZI,Recommendation for the diagnosis and treatment of novel coronavirus infection in children in Hubei (Trial version 1),10.1007/s12519-020-00343-7,,32051073,,"Since December 2019, a cluster of patients have been diagnosed to be infected with 2019 novel coronavirus (2019-nCoV) in Wuhan, China. The epidemic has been spreading to other areas of the country and abroad. A few cases have progressed rapidly to acute respiratory distress syndrome and/or multiple organ function failure. The epidemiological survey has indicated that the general population is susceptible to 2019-nCoV. A total of 14 children (6 months to 14 years of age, including 5 cases in Wuhan) have been confirmed to be infected with 2019-nCoV in China so far. In order to further standardize and enhance the clinical management of 2019-nCoV infection in children, reduce the incidence, and decrease the number of severe cases, we have formulated this diagnosis and treatment recommendation according to the recent information at home and abroad.",2020,"Pediatric Branch of Hubei Medical, Association; Pediatric Branch of Wuhan Medical, Association; Pediatric Medical Quality Control Center of, Hubei",Zhongguo Dang Dai Er Ke Za Zhi,3004896587,#813,
,CZI,Diagnosis and treatment of 2019 novel coronavirus infection in children: a pressing issue,10.1007/s12519-020-00344-6,,,,"Clinical features of infected pediatric patients The age of onset ranged from 1 month to 17 years in the 28 confirmed pediatric patients. All were family clusters or with a close contact history. The clinical features are variable in pediatric patients. Several patients displayed no obvious clinical symptoms at diagnosis, and they were found by screening because of close contacts with confirmed patients; and further chest imaging suggested pneumonia. Several gradually presented with fever, fatigue, dry cough, accompanied by other upper respiratory symptoms including nasal congestion, runny nose, and seldom gastrointestinal symptoms such as nausea, vomiting and diarrhea. Laboratory examination in pediatric patients showed that blood routine was often normal, and C-reactive protein was normal or transiently elevated. Lung imaging examination revealed mild increase of lung markings or ground-glass opacity or pneumoniaID - Shen2020",2020,"Shen, Kun-Ling; Yang, Yong-Hong",World Journal of Pediatrics,3004943457,#276,
,CZI,Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus,10.1007/s12519-020-00345-5,,,,"Since December 2019, an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China. As of 8 pm, 31 January 2020, more than 20 pediatric cases have been reported in China. Of these cases, ten patients were identified in Zhejiang Province, with an age of onset ranging from 112 days to 17 years. Following the latest National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCoV (the 4th edition) and current status of clinical practice in Zhejiang Province, recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health, the National Children’s Regional Medical Center, Children’s Hospital, Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.",2020,"Chen, Zhi-Min; Fu, Jun-Fen; Shu, Qiang; Chen, Ying-Hu; Hua, Chun-Zhen; Li, Fu-Bang; Lin, Ru; Tang, Lan-Fang; Wang, Tian-Lin; Wang, Wei; Wang, Ying-Shuo; Xu, Wei-Ze; Yang, Zi-Hao; Ye, Sheng; Yuan, Tian-Ming; Zhang, Chen-Mei; Zhang, Yuan-Yuan",World Journal of Pediatrics,3005489812,#334,
,CZI,New coronavirus: new challenges for pediatricians,10.1007/s12519-020-00346-4,,,,"Children comprise a special population whose immune response system is distinct from adults. Therefore, pediatric patients infected with 2019-nCoV have their own clinical features and therapeutic responses. Herein, we formulate this recommendation for diagnosis and treatment of 2019-nCoV infection in children which is of paramount importance for clinical practiceSN - 1867-0687",2020,"Chen, Zhi-Min; Fu, Jun-Fen; Shu, Qiang",World Journal of Pediatrics,3005938935,#572,
,CZI,Management strategies of neonatal jaundice during the coronavirus disease 2019 outbreak,10.1007/s12519-020-00347-3,,32112336,,"The outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV) has become a most challenging health emergency. Owing to rigorous quarantine and control measures taken in China, routine neonatal health surveillance and follow-up have become challenging. Without follow-up surveillance, some rapid and progressive newborn diseases, such as bilirubin encephalopathy, may be ignored. The characteristics of onset age of kernicterus suggest that monitoring of bilirubin level at home provides a useful way to alert hospital visits and to prevent the development of extremely hyperbilirubinemia. Therefore, we developed an online follow-up program for convenient monitoring of bilirubin level of newborns that is based on our practical experiences. The aim is to make our management strategies of neonatal jaundice tailored to the infection prevention and control during the COVID-19 epidemic.",2020,"Ma, X. L.; Chen, Z.; Zhu, J. J.; Shen, X. X.; Wu, M. Y.; Shi, L. P.; Du, L. Z.; Fu, J. F.; Shu, Q.",World journal of pediatrics : WJP,3004657851,#2898,
,CZI,Practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-nCoV) patients,10.1007/s12630-020-01591-x,,32052373,,"A global health emergency has been declared by the World Health Organization as the 2019-nCoV outbreak spreads across the world, with confirmed patients in Canada. Patients infected with 2019-nCoV are at risk for developing respiratory failure and requiring admission to critical care units. While providing optimal treatment for these patients, careful execution of infection control measures is necessary to prevent nosocomial transmission to other patients and to healthcare workers providing care. Although the exact mechanisms of transmission are currently unclear, human-to-human transmission can occur, and the risk of airborne spread during aerosol-generating medical procedures remains a concern in specific circumstances. This paper summarizes important considerations regarding patient screening, environmental controls, personal protective equipment, resuscitation measures (including intubation), and critical care unit operations planning as we prepare for the possibility of new imported cases or local outbreaks of 2019-nCoV. Although understanding of the 2019-nCoV virus is evolving, lessons learned from prior infectious disease challenges such as Severe Acute Respiratory Syndrome will hopefully improve our state of readiness regardless of the number of cases we eventually manage in Canada.",2020,"Wax, Randy S.; Christian, Michael D.",Can J Anaesth,3005561939,#874,
,CZI,What we do when a COVID-19 patient needs an operation: operating room preparation and guidance,10.1007/s12630-020-01617-4,,,,"We read with interest the recent review in the Journal by Wax and Christian1 on coronavirus disease 2019 (COVID-19). The first case of COVID-19 in Singapore was confirmed on 23 January 2020.2 In the week of February 13–19, the World Health Organization reported that Singapore had more cases of COVID-19 than any other country outside of mainland China.3 We wish to share the protocol that we use in our hospital in preparing an operating room (OR) for confirmed or suspected COVID-19 patients coming for surgery. An OR with a negative pressure environment located at a corner of the operating complex, and with a separate access, is designated for all confirmed (or suspected) COVID-19 cases. The OR actually consists of five interconnected rooms, of which only the ante room and anesthesia induction rooms have negative atmospheric pressures. The OR proper, preparation, and scrub rooms all have positive pressures (eFig. 1 in the Electronic Supplementary Material [ESM]). Understanding the airflow within the OR is crucial to minimizing the risk of infection. The same OR and the same anesthesia machine will only be used for COVID-19 cases for the duration of the epidemic. An additional heat and moisture exchanger (HME) filter is placed on the expiratory limb of the circuit. Both HME filters and the soda lime are changed after each case. The anesthetic drug trolley is kept in the induction room. Before the start of each operation, the anesthesiologist puts all the drugs and equipment required for the procedure onto a tray to avoid handling of the drug trolley during the case. Nevertheless, if there is a need for additional drugs, hand hygiene and glove changing are performed before entering the induction room and handling the drug trolley.SN - 1496-8975",2020,"Ti, Lian Kah; Ang, Lin Stella; Foong, Theng Wai; Ng, Bryan Su Wei",Canadian Journal of Anesthesia/Journal canadien d'anesthésie,2147204280,#5491,
,CZI,"Structural, glycosylation and antigenic variation between 2019 novel coronavirus (2019-nCoV) and SARS coronavirus (SARS-CoV)",10.1007/s13337-020-00571-5,,,,"The emergence of 2019 novel coronavirus (2019-nCoV) is of global concern and might have emerged from RNA recombination among existing coronaviruses. CoV spike (S) protein which is crucial for receptor binding, membrane fusion via conformational changes, internalization of the virus, host tissue tropism and comprises crucial targets for vaccine development, remain largely uncharacterized. Therefore, the present study has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which may be helpful for the management of 2019-nCoV infection. The sequences of spike glycoprotein of 2019-nCoV and SARS coronavirus (SARS-CoV) were used for the comparison. The sequence variations were determined using EMBOSS Needle pairwise sequence alignment tools. The variation in glycosylation sites was predicted by NetNGlyc 1.0 and validated by N-GlyDE server. Antigenicity was predicted by NetCTL 1.2 and validated by IEDB Analysis Resource server. The structural divergence was determined by using SuperPose Version 1.0 based on cryo-EM structure of the SARS coronavirus spike glycoprotein. Our data suggests that 2019-nCoV is newly spilled coronavirus into humans in China is closely related to SARS-CoV, which has only 12.8% of difference with SARS-CoV in S protein and has 83.9% similarity in minimal receptor-binding domain with SARS-CoV. Addition of a novel glycosylation sites were observed in 2019-nCoV. In addition, antigenic analysis proposes that great antigenic differences exist between both the viral strains, but some of the epitopes were found to be similar between both the S proteins. In spite of the variation in S protein amino acid composition, we found no significant difference in their structures. Collectively, for the first time our results exhibit the emergence of human 2019-nCoV is closely related to predecessor SARS-CoV and provide the evidence that 2019-nCoV uses various novel glycosylation sites as SARS-CoV and may have a potential to become pandemic owing its antigenic discrepancy. Further, demonstration of novel Cytotoxic T lymphocyte epitopes may impart opportunities for the development of peptide based vaccine for the prevention of 2019-nCoV.",2020,"Kumar, Swatantra; Maurya, Vimal K.; Prasad, Anil K.; Bhatt, Madan L. B.; Saxena, Shailendra K.",VirusDisease,3006282354,#4531,
,CZI,Coronavirus: Stehen wir am Beginn einer neuen Pandemie?,10.1007/s15006-020-0080-0,,,,"Beunruhigende Nachrichten aus China, erste Erkrankungsfälle in Europa. Das Coronoavirus breitet sich aus. MMW-Schriftleiter Prof. Johannes Bogner, München, berichtet aus infektiologischer Sicht über den derzeitigen Kenntnisstand und macht Sie zugleich fit für Fragen Ihrer Patienten.",2020,"Bogner, Johannes R.",MMW - Fortschritte der Medizin,3005035093,#144,
,CZI,2019 Novel coronavirus: where we are and what we know,10.1007/s15010-020-01401-y,,,,"There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.",2020,"Cheng, Zhangkai J.; Shan, Jing",Infection,3004114601,#1221,
,CZI,"Coronavirus outbreaks: prevention and management recommendationsAB - What role can pharmacists play? The International Pharmaceutical Federation is emphasizing the active role of community and hospital pharmacists can play in preventing the spread of COVID-19 [17]. Pharmacists are often a reliable and first point of contact for individuals having concerns or needing information and advice regarding ailments. Moreover, pharmacists are readily available at community pharmacies and hospital and accessible to the general population. Essential responsibilities of pharmacists include: having appropriate medicinal products in stock; promoting proper handwashing to prevent disease; controlling in-hospital infection; and providing patient care and support. Pharmacists also play a crucial role in the prevention, early detection of certain types of new cases and referring suspected cases to the relevant healthcare authorities [17].JO - Drugs & Therapy Perspectives",10.1007/s40267-020-00717-x,,,,,2020,"Khan, Zakir; Muhammad, Khayal; Ahmed, Ali; Rahman, Hazir",,2293363732,#4768,
,CZI,The SARS-CoV-2 Vaccine Pipeline: an Overview,10.1007/s40475-020-00201-6,,,,"The goal of this review is to provide a timely overview on efforts to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of coronavirus disease (COVID-19).",2020,"Chen, Wen-Hsiang; Strych, Ulrich; Hotez, Peter J.; Bottazzi, Maria Elena",Current Tropical Medicine Reports,2609522093,#3200,
,CZI,COVID-19: a critical care perspective informed by lessons learnt from other viral epidemics,10.1016/j.accpm.2020.02.002,,,,,2020,"Ling, Lowell; Joynt, Gavin M.; Lipman, Jeff; Constantin, Jean-Michel; Joannes-Boyau, Olivier",Anaesthesia Critical Care & Pain Medicine,2153224243,#1382,
,CZI,Coronavirus Disease 2019 (COVID-19): A critical care perspective beyond China,10.1016/j.accpm.2020.03.001,,,,,2020,"Rello, Jordi; Tejada, Sofia; Userovici, Caroline; Arvaniti, Kostoula; Pugin, Jérôme; Waterer, Grant",Anaesthesia Critical Care & Pain Medicine,2604381070,#4462,
,CZI,Corona Virus International Public Health Emergencies: Implications for Radiology Management,10.1016/j.acra.2020.02.003,,,,"The outbreak of 2019 novel coronavirus (2019-nCoV) pneumonia was reported in Wuhan, Hubei Province, China in December 2019 and has spread internationally. This article discusses how radiology departments can most effectively respond to this public health emergency.",2020,"Zhang, Han-Wen; Yu, Juan; Xu, Hua-Jian; Lei, Yi; Pu, Zu-Hui; Dai, Wei-Cai; Lin, Fan; Wang, Yu-Li; Wu, Xiao-Liu; Liu, Li-Hong; Li, Min; Mo, Yong-Qian; Zhang, Hong; Luo, Si-Ping; Chen, Huan; Lyu, Gui-Wen; Zhou, Zhao-Guang; Liu, Wei-Min; Liu, Xiao-Lei; Song, Hai-Yan; Chen, Fu-Zhen; Zeng, Liang; Zhong, Hua; Guo, Ting-Ting; Hu, Ya-Qiong; Yang, Xin-Xin; Liu, Pin-Ni; Li, Ding-Fu",Academic Radiology,2380955547,#2064,
,CZI,"A climatologic investigation of the SARS-CoV outbreak in Beijing, China",10.1016/j.ajic.2005.12.006,,,,"The first cases of severe acute respiratory syndrome (SARS) were identified in November 2002, in Guangdong Province, China. The epidemic spread rapidly within China and internationally, with 8454 recorded infections and 792 deaths by June 15, 2003. Temperature, relative humidity, and wind velocity were the three key meteorological determinants affecting the transmission of SARS. The peak spread of SARS occurred at a mean temperature of 16.9 degrees C (95% CI, 10.7 degrees C to 23.1 degrees C), with a mean relative humidity of 52.2% (95% CI, 33.0% to 71.4%) and wind speed of 2.8 ms(-1) (95% CI, 2.0 to 3.6 ms(-1)). In northern China, these conditions are most likely to occur in the spring and suggest that SARS has a seasonal nature akin to viruses such as influenza and the common cold. A regression equation (Y=218.692-0.698X(t)-2.043X(h)+2.282X(w)) was derived to represent the optimal climatic conditions for the 2003 SARS epidemic. Further investigations in other regions are necessary to verify these results.",2006,"Yuan, J.; Yun, H.; Lan, W.; Wang, W.; Sullivan, S. G.; Jia, S.; Bittles, A. H.",American Journal of Infection Control,1963995582,#2072,
,CZI,A systematic risk-based strategy to select personal protective equipment for infectious diseases,10.1016/j.ajic.2019.06.023,,,,"Background: Personal protective equipment (PPE) is a primary strategy to protect health care personnel (HCP) from infectious diseases. When transmission-based PPE ensembles are not appropriate, HCP must recognize the transmission pathway of the disease and anticipate the exposures to select PPE. Because guidance for this process is extremely limited, we proposed a systematic, risk-based approach to the selection and evaluation of PPE ensembles to protect HCP against infectious diseases. Methods: The approach used in this study included the following 4 steps: (1) job hazard analysis, (2) infectious disease hazard analysis, (3) selection of PPE, and (4) evaluation of selected PPE. Selected PPE should protect HCP from exposure, be usable by HCP, and fit for purpose. Results: The approach was demonstrated for the activity of intubation of a patient with methicillin-resistant Staphylococcus aureus or Severe Acute Respiratory Syndrome coronavirus. As expected, the approach led to the selection of different ensembles of PPE for these 2 pathogens. Discussion: A systematic risk-based approach to the selection of PPE will help health care facilities and HCP select PPE when transmission-based precautions are not appropriate. Owing to the complexity of PPE ensemble selection and evaluation, a team with expertise in infectious diseases, occupational health, the health care activity, and related disciplines, such as human factors, should be engaged. Conclusions: Participation, documentation, and transparency are necessary to ensure the decisions can be communicated, critiqued, and understood by HCP. (C) 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.",2020,"Jones, Rachael M.; Bleasdale, Susan C.; Maita, Dayana; Brosseau, Lisa M.; Program, C. D. C. Prevention Epictr",American Journal of Infection Control,2964662575,#3682,
,CZI,Coronavirus Disease 2019 (COVID-19) and Pregnancy: What obstetricians need to know,10.1016/j.ajog.2020.02.017,,,,"Coronavirus Disease 2019 (COVID-19) is an emerging disease with a rapid increase in cases and deaths since its first identification in Wuhan, China, in December 2019. Limited data are available about COVID-19 during pregnancy; however, information on illnesses associated with other highly pathogenic coronaviruses (i.e., severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS)) might provide insights into COVID-19’s effects during pregnancy.",2020,"Rasmussen, Sonja A.; Smulian, John C.; Lednicky, John A.; Wen, Tony S.; Jamieson, Denise J.",American Journal of Obstetrics and Gynecology,2604381070,#1778,
,CZI,Fear of COVID 2019: First suicidal case in India !,10.1016/j.ajp.2020.101989,,,,,2020,"Goyal, Kapil; Chauhan, Poonam; Chhikara, Komal; Gupta, Parakriti; Singh, Mini P.",Asian Journal of Psychiatry,1995569061,#2278,
,CZI,Iranian mental health during the COVID-19 epidemic,10.1016/j.ajp.2020.101990,,,,,2020,"Zandifar, Atefeh; Badrfam, Rahim",Asian Journal of Psychiatry,2959884400,#4381,
,CZI,SARS-CoV-2: a novel deadly virus in a globalised world,10.1016/j.antiviral.2005.10.005,,32078595,,,2020,"Dilcher, Meik; Werno, Anja; Jennings, Lance C.",N Z Med J,2047323912,#1662,
,CZI,Comparison of broad-spectrum antiviral activities of the synthetic rocaglate CR-31-B (−) and the eIF4A-inhibitor Silvestrol,10.1016/j.antiviral.2020.104706,,,,"Rocaglates, a class of natural compounds isolated from plants of the genus Aglaia, are potent inhibitors of translation initiation. They are proposed to form stacking interactions with polypurine sequences in the 5′-untranslated region (UTR) of selected mRNAs, thereby clamping the RNA substrate onto eIF4A and causing inhibition of the translation initiation complex. Since virus replication relies on the host translation machinery, it is not surprising that the rocaglate Silvestrol has broad-spectrum antiviral activity. Unfortunately, synthesis of Silvestrol is sophisticated and time-consuming, thus hampering the prospects for further antiviral drug development. Here, we present the less complex structured synthetic rocaglate CR-31-B (−) as a novel compound with potent broad-spectrum antiviral activity in primary cells and in an ex vivo bronchial epithelial cell system. CR-31-B (−) inhibited the replication of corona-, Zika-, Lassa-, Crimean Congo hemorrhagic fever viruses and, to a lesser extent, hepatitis E virus (HEV) at non-cytotoxic low nanomolar concentrations. Since HEV has a polypurine-free 5′-UTR that folds into a stable hairpin structure, we hypothesized that RNA clamping by Silvestrol and its derivatives may also occur in a polypurine-independent but structure-dependent manner. Interestingly, the HEV 5′-UTR conferred sensitivity towards Silvestrol but not to CR-31-B (−). However, if an exposed polypurine stretch was introduced into the HEV 5′-UTR, CR-31-B (−) became an active inhibitor comparable to Silvestrol. Moreover, thermodynamic destabilization of the HEV 5′-UTR led to reduced translational inhibition by Silvestrol, suggesting differences between rocaglates in their mode of action, most probably by engaging Silvestrol's additional dioxane moiety.",2020,"Müller, Christin; Obermann, Wiebke; Schulte, Falk W.; Lange-Grünweller, Kerstin; Oestereich, Lisa; Elgner, Fabian; Glitscher, Mirco; Hildt, Eberhard; Singh, Kamini; Wendel, Hans-Guido; Hartmann, Roland K.; Ziebuhr, John; Grünweller, Arnold",Antiviral Research,,#2162,
,CZI,The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade,10.1016/j.antiviral.2020.104742,,,,"In 2019, a new coronavirus (2019-nCoV) infecting Humans has emerged in Wuhan, China. Its genome has been sequenced and the genomic information promptly released. Despite a high similarity with the genome sequence of SARS-CoV and SARS-like CoVs, we identified a peculiar furin-like cleavage site in the Spike protein of the 2019-nCoV, lacking in the other SARS-like CoVs. In this article, we discuss the possible functional consequences of this cleavage site in the viral cycle, pathogenicity and its potential implication in the development of antivirals.",2020,"Coutard, B.; Valle, C.; de Lamballerie, X.; Canard, B.; Seidah, N. G.; Decroly, E.",Antiviral Research,3005409321,#624,
,CZI,Of chloroquine and COVID-19,10.1016/j.antiviral.2020.104762,,,,"Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel emerged coronavirus (SARS-CoV-2). The scientific community should consider this information in light of previous experiments with chloroquine in the field of antiviral research.",2020,"Touret, Franck; de Lamballerie, Xavier",Antiviral Research,3006304371,#4426,
,CZI,Recent advances in lab-on-a-chip technologies for viral diagnosis,10.1016/j.bios.2020.112041,,,,"The global risk of viral disease outbreaks emphasizes the need for rapid, accurate, and sensitive detection techniques to speed up diagnostics allowing early intervention. An emerging field of microfluidics also known as the lab-on-a-chip (LOC) or micro total analysis system includes a wide range of diagnostic devices. This review briefly covers both conventional and microfluidics-based techniques for rapid viral detection. We first describe conventional detection methods such as cell culturing, immunofluorescence or enzyme-linked immunosorbent assay (ELISA), or reverse transcription polymerase chain reaction (RT-PCR). These methods often have limited speed, sensitivity, or specificity and are performed with typically bulky equipment. Here, we discuss some of the LOC technologies that can overcome these demerits, highlighting the latest advances in LOC devices for viral disease diagnosis. We also discuss the fabrication of LOC systems to produce devices for performing either individual steps or virus detection in samples with the sample to answer method. The complete system consists of sample preparation, and ELISA and RT-PCR for viral-antibody and nucleic acid detection, respectively. Finally, we formulate our opinions on these areas for the future development of LOC systems for viral diagnostics.",2020,"Zhu, Hanliang; Fohlerová, Zdenka; Pekárek, Jan; Basova, Evgenia; Neužil, Pavel",Biosensors and Bioelectronics,3002683399,#156,
,CZI,Outbreak of a new coronavirus: what anaesthetists should know,10.1016/j.bja.2020.02.008,,32115186,,,2020,"Peng, Philip W. H.; Ho, Pak-Leung; Hota, Susy S.",British journal of anaesthesia,2044189336,#3894,
,CZI,Laboratory biosafety guide for the novel coronavirus,10.1016/j.bsheal.2020.01.001,,,,,2020,"Department of Health Science, Technology; Education, National Health Commission of People's Republic of China",Biosafety and Health,2619475730,#119,
,CZI,Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis,10.1016/j.cca.2020.03.004,,,,,2020,"Lippi, Giuseppe; Plebani, Mario",Clinica Chimica Acta,3006645647,#4506,
,CZI,"Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in Wuhan, China, from Jan to Feb 2020",10.1016/j.cca.2020.03.009,,,,"Background There’s an outbreak of a novel coronavirus (SARS-CoV-2) infection since December 2019, first in China, and currently with more than 80 thousand confirmed infection globally in 29 countries till March 2, 2020. Identification, isolation and caring for patients early are essential to limit human-to-human transmission including reducing secondary infections among close contacts and health care workers, preventing transmission amplification events. The RT-PCR detection of viral nucleic acid test (NAT) was one of the most quickly established laboratory diagnosis method in a novel viral pandemic, just as in this COVID-19 outbreak. Methods 4880 cases that had respiratory infection symptoms or close contact with COVID-19 patients in hospital in Wuhan, China, were tested for SARS-CoV-2 infection by use of quantitative RT-PCR (qRT-PCR) on samples from the respiratory tract. Positive rates were calculated in groups divided by genders or ages. Results The positive rate was about 38% for the total 4880 specimens. Male and older population had a significant higher positive rates. However, 57% was positive among the specimens from the Fever Clinics. Binary logistic regression analysis showed that age, not gender, was the risk factor for SARS-CoV-2 infection in fever clinics. Conclusions Therefore, we concluded that viral NAT played an important role in identifying SARS-CoV-2 infection.",2020,"Liu, Rui; Han, Huan; Liu, Fang; Lv, Zhihua; Wu, Kailang; Liu, Yingle; Feng, Yong; Zhu, Chengliang",Clinica Chimica Acta,2053972970,#5447,
,CZI,The Novel Coronavirus Outbreak: What We Know and What We Don&#x2019;t,10.1016/j.cell.2020.02.027,,,,"Phylogenetic analyses reveal that SARS-CoV-2 is closely related to a group of SARS-like coronaviruses. However, it remains unclear where the virus comes from and how it was transmitted to humans in the first place. Unlike with other zoonotic agents such as hantavirus and arenavirus, thus far we haven’t found a SARS virus in animals that is the same as that in humans. Fortunately, SARS virus has not appeared in humans since 2004. In contrast, this new virus seems to have stronger transmission capabilities among people. Compared to the primary virus in humans, we still know less about whether, what, and how the virus has changed and the effect of the changes for their epidemics in humans. Control and prevention of the disease is especially difficult in China and elsewhere if there are infected individuals with no clinical signs.",2020,,Cell,2405540444,#1886,
,CZI,SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor,10.1016/j.cell.2020.02.052,,,,"The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.",,"Hoffmann, Markus; Kleine-Weber, Hannah; Schroeder, Simon; Krüger, Nadine; Herrler, Tanja; Erichsen, Sandra; Schiergens, Tobias S.; Herrler, Georg; Wu, Nai-Huei; Nitsche, Andreas; Müller, Marcel A.; Drosten, Christian; Pöhlmann, Stefan",Cell,3006448444,#4561,
,CZI,A novel coronavirus (COVID-19) outbreak: a call for action,10.1016/j.chest.2020.02.014,,,,,2020,"Zhang, Yi; Xu, Jiuyang; Li, Hui; Cao, Bin",Chest,3005943294,#1256,
,CZI,Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China,10.1016/j.chom.2020.02.001,,,,"An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.",2020,"Wu, Aiping; Peng, Yousong; Huang, Baoying; Ding, Xiao; Wang, Xianyue; Niu, Peihua; Meng, Jing; Zhu, Zhaozhong; Zhang, Zheng; Wang, Jiangyuan; Sheng, Jie; Quan, Lijun; Xia, Zanxian; Tan, Wenjie; Cheng, Genhong; Jiang, Taijiao",Cell Host & Microbe,3004896487,#546,
,CZI,Asymptomatic novel coronavirus pneumonia patient outside WuHan: The value of CT images in the course of the disease,10.1016/j.clinimag.2020.02.008,,,,"The purpose of this case report is to describe the imaging and associated clinical features of an asymptomatic novel coronavirus pneumonia (COVID-19) patient outside WuHan, China. The principle findings are that in this patient with laboratory-confirmed COVID-19, CT findings preceded symptoms and included bilateral pleural effusions, previously not reported in association with COVID-19. The role of this case report is promotion of potential recognition amongst radiologists of this new disease, which has been declared a global health emergency by the World Health Organization (WHO).",2020,"Lin, Chen; Ding, Yuxiao; Xie, Bin; Sun, Zhujian; Li, Xiaogang; Chen, Zixian; Niu, Meng",Clinical Imaging,3004511262,#1575,
,CZI,Novel coronavirus: how things are in Wuhan,10.1016/j.cmi.2020.02.005,,,,,2020,"Khan, S.; Nabi, G.; Han, G.; Siddique, R.; Lian, S.; Shi, H.; Bashir, N.; Ali, A.; Shereen, M. A.",Clinical Microbiology and Infection,3006085809,#3378,
,CZI,"First Atypical case of 2019 novel coronavirus in Yan'an, China",10.1016/j.cmi.2020.02.011,,,,,2020,"Hao, Wendong; Li, Manxiang; Huang, Xiaoqi",Clinical Microbiology and Infection,3004790666,#1303,
,CZI,"Computers and viral diseases. Preliminary bioinformatics studies on the design of a synthetic vaccine and a preventative peptidomimetic antagonist against the SARS-CoV-2 (2019-nCoV, COVID-19) coronavirus",10.1016/j.compbiomed.2020.103670,,,,"This paper concerns study of the genome of the Wuhan Seafood Market isolate believed to represent the causative agent of the disease COVID-19. This is to find a short section or sections of viral protein sequence suitable for preliminary design proposal for a peptide synthetic vaccine and a peptidomimetic therapeutic, and to explore some design possibilities. The project was originally directed towards a use case for the Q-UEL language and its implementation in a knowledge management and automated inference system for medicine called the BioIngine, but focus here remains mostly on the virus itself. However, using Q-UEL systems to access relevant and emerging literature, and to interact with standard publically available bioinformatics tools on the Internet, did help quickly identify sequences of amino acids that are well conserved across many coronaviruses including 2019-nCoV. KRSFIEDLLFNKV was found to be particularly well conserved in this study and corresponds to the region around one of the known cleavage sites of the SARS virus that are believed to be required for virus activation for cell entry. This sequence motif and surrounding variations formed the basis for proposing a specific synthetic vaccine epitope and peptidomimetic agent. The work can, nonetheless, be described in traditional bioinformatics terms, and readily reproduced by others, albeit with the caveat that new data and research into 2019-nCoV is emerging and evolving at an explosive pace. Preliminary studies using molecular modeling and docking, and in that context the potential value of certain known herbal extracts, are also described.",2020,"Robson, B.",Computers in Biology and Medicine,1655564745,#1938,
,CZI,"History is repeating itself, a probable zoonotic spillover as a cause of an epidemic: the case of 2019 novel Coronavirus",10.1016/j.cortex.2016.02.016,,32009128,,"Pathogen transmission from a vertebrate animal to a human, also known as zoonotic spillover, represents a global public health burden, which while associated with multiple outbreaks, still remains a poorly understood phenomenon. Coronaviruses, like influenza viruses, circulate in nature in various animal species. Alpha-coronaviruses and beta-coronaviruses can infect mammals and gamma-coronaviruses and delta-coronaviruses tend to infect birds, but some of them can also be transmitted to mammals. Although still preliminary, current data suggest that bats are the most probable initial source of the current 2019 novel CoV (2019nCoV) outbreak, that begun on December 2019 in Wuhan, China, apparently spreading from a ""wet market"" to multiple cities and provinces in China. This epidemic of 2019nCoV, already reaching more than 6,000 cases to-day (end of January 2020) (>90% in China), will not be the last one linked to zoonotic spillover events.",2020,"Rodriguez-Morales, Alfonso J.; Bonilla-Aldana, D. Katterine; Balbin-Ramon, Graciela Josefina; Rabaan, Ali A.; Sah, Ranjit; Paniz-Mondolfi, Alberto; Pagliano, Pasquale; Esposito, Silvano",Infez Med,2297614983,#277,
,CZI,New thinking in the treatment of 2019 novel coronavirus pneumonia,10.1016/j.ctcp.2020.101131,,,,,2020,"Yang, Qing-Xin; Zhao, Ting-Hui; Sun, Chong-Zhou; Wu, Li-Meng; Dai, Qiang; Wang, Shuai-dao; Tian, Hui",Complementary Therapies in Clinical Practice,3004824173,#4388,
,CZI,Effects of progressive muscle relaxation on anxiety and sleep quality in patients with COVID-19,10.1016/j.ctcp.2020.101132,,,,"Background Patients with Coronavirus Disease 2019(COVID-19) will experience high levels of anxiety and low sleep quality due to isolation treatment. Some sleep-improving drugs may inhibit the respiratory system and worsen the condition. Prolonged bedside instruction may increase the risk of medical infections. Objective To investigate the effect of progressive muscle relaxation on anxiety and sleep quality of COVID-19. Methods In this randomized controlled clinical trial, a total of 51 patients who entered the isolation ward were included in the study and randomly divided into experimental and control groups. The experimental group used progressive muscle relaxation (PMR) technology for 30 min per day for 5 consecutive days. During this period, the control group received only routine care and treatment. Before and after the intervention, the Spielberger State-Trait Anxiety Scale (STAI) and Sleep State Self-Rating Scale (SRSS) were used to measure and record patient anxiety and sleep quality. Finally, data analysis was performed using SPSS 25.0 software. Results The average anxiety score (STAI) before intervention was not statistically significant (P = 0.730), and the average anxiety score after intervention was statistically significant (P < 0.001). The average sleep quality score (SRSS) of the two groups before intervention was not statistically significant (P = 0.838), and it was statistically significant after intervention (P < 0.001). Conclusion Progressive muscle relaxation as an auxiliary method can reduce anxiety and improve sleep quality in patients with COVID-19.",2020,"Liu, Kai; Chen, Ying; Wu, Duozhi; Lin, Ruzheng; Wang, Zaisheng; Pan, Liqing",Complementary Therapies in Clinical Practice,2904096912,#4505,
,CZI,Recent discovery and development of inhibitors targeting coronaviruses,10.1016/j.drudis.2020.01.015,,,,"Human coronaviruses (CoVs) are enveloped viruses with a positive-sense single-stranded RNA genome. Currently, six human CoVs have been reported including human coronavirus 229E (HCoV-229E), OC43 (HCoV-OC43), NL63 (HCoV-NL63), HKU1 (HCoV-HKU1), severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and MiddleEast respiratory syndrome (MERS) coronavirus (MERS-CoV). They cause moderate to severe respiratory and intestinal infections in humans. In this review, we focus on recent advances in the research and development of small-molecule anti-human coronavirus therapies targeting different stages of the CoV life cycle. Recent advances in the research and development of small-molecule anti-human coronavirus therapies.",2020,"Pillaiyar, T.; Meenakshisundaram, S.; Manickam, M.",Drug Discovery Today,3003448227,#2569,
,CZI,Comparison of pulmonary availability and anti-inflammatory effect of dehydroandrographolide succinate via intratracheal and intravenous administration,10.1016/j.ejps.2020.105290,,,,"Dehydroandrographolide succinate (DAS) injection, which was approved in China for the treatment of viral pneumonia and upper respiratory tract infections, is often off-label used for nebulization therapy to avoid the adverse drug reactions associated with the injection. However, the aerodynamic properties and pulmonary fate of nebulized DAS was largely uninvestigated. In this study, the main objectives were to evaluate the in vitro aerodynamic deposition profiles of nebulizer generated aerosols and comparatively investigate the local drug availability and anti-inflammatory efficacy of DAS between intratracheal and intravenous dosing. The in vitro evaluation of aerodynamic characteristics and droplet size distribution showed more than 50% aerosol particles with size being < 5 μm, allowing the aerosols to reach the lower respiratory tract. Following intratracheal administration, the drug underwent pulmonary absorption into the bloodstream, rendering an absolute bioavailability of 47.3%. Compared to the intravenous delivery, the intratracheal administration dramatically increased the drug availability in the lung tissue in rats by more than 80-fold, leading to an improved and prolonged local anti-inflammatory efficacy in a lipopolysaccharide induced lung injury model in mice. The present results demonstrated that inhalation delivery of DAS is a convenient and effective alternative to intravenous injections.",2020,"Wei-Ya, Chen; Yuan-Song, Wang; Chun-Yu, Liu; Yu-Bin, Ji; Fei-Fei, Yang; Yong-Hong, Dr Liao",European Journal of Pharmaceutical Sciences,1978908825,#3102,
,CZI,A new pandemic out of China: the Wuhan 2019-nCoV coronavirus syndrome,10.1016/j.hlpt.2020.02.001,,,,,2020,"Singer, D. R. J.",Health Policy and Technology,3004825441,#1496,
,CZI,Strengthening ICU health security for a coronavirus epidemic,10.1016/j.iccn.2020.102812,,,,,2020,"Jansson, Miia; Liao, Xuelian; Rello, Jordi",Intensive and Critical Care Nursing,3004798505,#539,
,CZI,"Real-time forecasts of the COVID-19 epidemic in China from February 5th to February 24th, 2020",10.1016/j.idm.2020.02.002,,,,"The initial cluster of severe pneumonia cases that triggered the COVID-19 epidemic was identified in Wuhan, China in December 2019. While early cases of the disease were linked to a wet market, human-to-human transmission has driven the rapid spread of the virus throughout China. The Chinese government has implemented containment strategies of city-wide lockdowns, screening at airports and train stations, and isolation of suspected patients; however, the cumulative case count keeps growing every day. The ongoing outbreak presents a challenge for modelers, as limited data are available on the early growth trajectory, and the epidemiological characteristics of the novel coronavirus are yet to be fully elucidated.We use phenomenological models that have been validated during previous outbreaks to generate and assess short-term forecasts of the cumulative number of confirmed reported cases in Hubei province, the epicenter of the epidemic, and for the overall trajectory in China, excluding the province of Hubei. We collect daily reported cumulative confirmed cases for the 2019-nCoV outbreak for each Chinese province from the National Health Commission of China. Here, we provide 5, 10, and 15 day forecasts for five consecutive days, February 5th through February 9th, with quantified uncertainty based on a generalized logistic growth model, the Richards growth model, and a sub-epidemic wave model.Our most recent forecasts reported here, based on data up until February 9, 2020, largely agree across the three models presented and suggest an average range of 7409–7496 additional confirmed cases in Hubei and 1128–1929 additional cases in other provinces within the next five days. Models also predict an average total cumulative case count between 37,415 and 38,028 in Hubei and 11,588–13,499 in other provinces by February 24, 2020.Mean estimates and uncertainty bounds for both Hubei and other provinces have remained relatively stable in the last three reporting dates (February 7th – 9th). We also observe that each of the models predicts that the epidemic has reached saturation in both Hubei and other provinces. Our findings suggest that the containment strategies implemented in China are successfully reducing transmission and that the epidemic growth has slowed in recent days. Keywords: COVID-19, Coronavirus, China, Real-time forecasts, Phenomenological models",2020,"Chowell, K. Roosa; Lee, Y.; Luo, R.; Kirpich, A.; Rothenberg, R.; Hyman, J. M.; Yan, P.; G",Infectious Disease Modelling,3006028741,#1669,
,CZI,Chloroquine for the 2019 novel coronavirus SARS-CoV-2,10.1016/j.ijantimicag.2020.105923,,32070753,,,2020,"Colson, Philippe; Rolain, Jean-Marc; Raoult, Didier",International journal of antimicrobial agents,3006128040,#4035,
,CZI,Management of corona virus disease-19 (COVID-19): the Zhejiang experience,10.1016/j.ijantimicag.2020.105924,,32096367,,"The current epidemic situation of corona virus disease-19 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 inZhejiang Province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on ""Four-Anti and Two-Balance"" for clinical practice. The ""Four-Anti and Two-Balance""strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinarypersonalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in10% patients'blood samples at acute periodand 50% of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifyingcytokine storms and application of artificial liver blood purification system. The ""Four-Anti and Two-Balance""strategyeffectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviraleffects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favoredthe balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short periods of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis should be prescribed rationally and was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbialdysbiosis with decreasedprobiotics such as Lactobacillus and Bifidobacterium. Nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore, we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the SARS-CoV-2 infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience above and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.",2020,"Xu, Kaijin; Cai, Hongliu; Shen, Yihong; Ni, Qin; Chen, Yu; Hu, Shaohua; Li, Jianping; Wang, Huafen; Yu, Liang; Huang, He; Qiu, Yunqing; Wei, Guoqing; Fang, Qiang; Zhou, Jianying; Sheng, Jifang; Liang, Tingbo; Li, Lanjuan",Zhejiang Da Xue Xue Bao Yi Xue Ban,3006645647,#1909,
,CZI,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and corona virus disease-2019 (COVID-19): the epidemic and the challenges,10.1016/j.ijantimicag.2020.105924,,,,"ABSTRACT Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously provisionally named 2019 novel coronavirus or 2019-nCoV) disease (COVID-19) in China at the end of 2019, has caused a large global outbreak and a major public health issue. As of February 11, 2020, data from the WHO has shown that more than 43,000 confirmed cases have been identified in 28 countries/regions, with more than 99% of the cases being detected in China. On January 30, 2020, WHO has declared COVID-19 as the sixth public health emergency of international concern. The SARS-CoV-2 is closely related to two bat-derived severe acute respiratory syndrome-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. It is spread by human-to-human transmission via droplets or direct contact, and infection has been estimated to have mean incubation period of 6.4 days and a basic reproduction number of 2.24-3.58. Among the patients with pneumonia caused by the SARS-CoV-2 (novel coronavirus pneumonia or Wuhan pneumonia), fever was the most common symptom, followed by cough. Bilateral lung involvement with ground glass opacity was the most common finding from computerized tomography images of the chest. Although the one case of SARS-CoV-2 pneumonia in the United States responding well to remdesivir, which is now undergoing a clinical trial in China. Currently, controlling infection to prevent the spread of the SARS-CoV-2 is the primary intervention being used. However, public health authorities should keep monitoring the situation closely, as the more we can learn about this novel virus and its associated outbreak, the better we can respond.",2020,"Lai, Chih-Cheng; Shih, Tzu-Ping; Ko, Wen-Chien; Tang, Hung-Jen; Hsueh, Po-Ren",International Journal of Antimicrobial Agents,3006645647,#1132,
,CZI,Chloroquine and hydroxychloroquine as available weapons to fight COVID-19,10.1016/j.ijantimicag.2020.105932,,,,,2020,"Colson, Philippe; Rolain, Jean-Marc; Lagier, Jean-Christophe; Brouqui, Philippe; Raoult, Didier",International Journal of Antimicrobial Agents,3006128040,#4597,
,CZI,Arguments in favor of remdesivir for treating SARS-CoV-2 infections,10.1016/j.ijantimicag.2020.105933,,,,,2020,"Ko, Wen-Chien; Rolain, Jean-Marc; Lee, Nan-Yao; Chen, Po-Lin; Huang, Ching-Tai; Lee, Ping-Ing; Hsueh, Po-Ren",International Journal of Antimicrobial Agents,3006645647,#4533,
,CZI,"Short-term effects of ambient PM1 and PM2.5 air pollution on hospital admission for respiratory diseases: Case-crossover evidence from Shenzhen, China",10.1016/j.ijheh.2019.11.001,,,,"Background Ambient PM1 (particulate matter with aerodynamic diameter ≤1 μm) is an important contribution of PM2.5 mass. However, little is known worldwide regarding the PM1-associated health effects due to a wide lack of ground-based PM1 measurements from air monitoring stations. Methods We collected daily records of hospital admission for respiratory diseases and station-based measurements of air pollution and weather conditions in Shenzhen, China, 2015–2016. Time-stratified case-crossover design and conditional logistic regression models were adopted to estimate hospitalization risks associated with short-term exposures to PM1 and PM2.5. Results PM1 and PM2.5 showed significant adverse effects on respiratory disease hospitalizations, while no evident associations with PM1–2.5 were identified. Admission risks for total respiratory diseases were 1.09 (95% confidence interval: 1.04 to 1.14) and 1.06 (1.02 to 1.10), corresponding to per 10 μg/m3 rise in exposure to PM1 and PM2.5 at lag 0–2 days, respectively. Both PM1 and PM2.5 were strongly associated with increased admission for pneumonia and chronic obstructive pulmonary diseases, but exhibited no effects on asthma and upper respiratory tract infection. Largely comparable risk estimates were observed between male and female patients. Groups aged 0–14 years and 45–74 years were significantly affected by PM1- and PM2.5-associated risks. PM-hospitalization associations exhibited a clear seasonal pattern, with significantly larger risks in cold season than those in warm season among some subgroups. Conclusions Our study suggested that PM1 rather than PM1–2.5 contributed to PM2.5-induced risks of hospitalization for respiratory diseases and effects of PM1 and PM2.5 mainly occurred in cold season.",2020,"Zhang, Yunquan; Ding, Zan; Xiang, Qianqian; Wang, Wei; Huang, Li; Mao, Feiyue",International Journal of Hygiene and Environmental Health,2989937665,#3088,
,CZI,First respiratory transmitted food borne outbreak?,10.1016/j.ijheh.2020.113490,,32088598,,"The world is faced with a remarkable coronavirus outbreak with epicentre in Wuhan, China. Altogether 40554 cases have been confirmed globally with novel coronavirus (SARS-CoV-2) until February 10, 2020. Rigorous surveillance in other countries is required to prevent further global expansion of the outbreak, but resolving the exact mechanism of the initial transmission events is crucial. Most initial cases had visited Huanan South Seafood Market in Wuhan selling also various exotic live animals. Based on the limited initial human-to-human transmission and timely clustering of cases in Huanan market among elderly men, coupled with knowledge that coronaviruses are derived from animals and relationship of SARS-CoV-2 to bat coronavirus, zoonotic transmission in the first instance is probable. To target the actions, similar epidemiological actions to human cases are needed with animal or food exposures. According to current information, an exceptionally wide contamination of seafood market might explain the initiation of the SARS-CoV-2 outbreak. Seafood tanks, air contamination by live animals or rodents are possibilities, but sold animals normally come from various sources. The mode of transmission may become clearer in future: usually in outbreak investigations, hindsight is easy, but for now information about the initial source of this outbreak is limited.",2020,"Jalava, Katri",Int J Hyg Environ Health,2092729099,#1832,
,CZI,The 2019 Novel Coronavirus Outbreak - A Global Threat,10.1016/j.ijid.2020.01.009,,32138488,,"The 2019 Novel Corona virus infection (COVID 19) is an ongoing public health emergency of international significance. There are significant knowledge gaps in the epidemiology, transmission dynamics, investigation tools and management. In this article, we review the available evidence about this disease. Every decade has witnessed the evolution of a new coronavirus epidemic since the last three decades. The varying transmission patterns, namely, nosocomial transmission and spread through mildly symptomatic cases is an area of concern. There is a spectrum of clinical features from mild to severe life threatening disease with major complications like severe pneumonia, ARDS, acute cardiac injury and septic shock. Presence of bilateral ground glass opacity and consolidation on imaging in appropriate clinical background should raise a suspicion about COVID 19. Poor prognostic factors include Multilobular infiltration on chest imaging, Lymphopenia, Bacterial co-infection, Smoking history, Chronic medical conditions like Hypertension and age >60 years (MuLBSTA score). Diagnosis is confirmed with PCR based testing of appropriate respiratory samples. Management is primarily supportive, with newer antivirals (lopinavir ritonavir and Remdesivir) under investigation. Role of steroids is still inconclusive. Standard infection control and prevention techniques should be followed. Vigilant screening of suspected cases and their contacts is important. Isolation of symptomatic cases and home quarantine of asymptomatic contacts is recommended. To conclude, controlling this highly transmissible disease requires international co-ordination.",2020,"Khot, W. Y.; Nadkar, M. Y.",The Journal of the Association of Physicians of India,2999409984,#4769,
,CZI,"Comments on ""Preliminary estimation of the basic reproduction number of novel Coronavirus (2019-nCoV) in China, from 2019 to 2020: A data-driven Analysis in the early phase of the outbreak""",10.1016/j.ijid.2020.02.024,,,,,2020,"Dhungana, Hom Nath",International Journal of Infectious Diseases,3004397688,#1403,
,CZI,The basic reproduction number of novel coronavirus (2019-nCoV) estimation based on exponential growth in the early outbreak in China from 2019 to 2020: A reply to Dhungana,10.1016/j.ijid.2020.02.025,,,,,2020,"Zhao, Shi; Lin, Qianyin; Ran, Jinjun; Musa, Salihu S.; Yang, Guangpu; Wang, Weiming; Lou, Yijun; Gao, Daozhou; Yang, Lin; He, Daihai; Wang, Maggie H.",International Journal of Infectious Diseases,3004397688,#1345,
,CZI,2019-novel Coronavirus severe adult respiratory distress syndrome in two cases in Italy: An uncommon radiological presentation,10.1016/j.ijid.2020.02.043,,,,"Introduction Several recent case reports have described common early chest imaging findings of lung pathology caused by 2019 novel Coronavirus (SARS-COV2) which appear to be similar to those seen previously in SARS-CoV and MERS-CoV infected patients. Objective We present some remarkable imaging findings of the first two patients identified in Italy with COVID-19 infection travelling from Wuhan, China. The follow-up with chest X-Rays and CT scans was also included, showing a progressive adult respiratory distress syndrome (ARDS). Results Moderate to severe progression of the lung infiltrates, with increasing percentage of high-density infiltrates sustained by a bilateral and multi-segmental extension of lung opacities, were seen. During the follow-up, apart from pleural effusions, a tubular and enlarged appearance of pulmonary vessels with a sudden caliber reduction was seen, mainly found in the dichotomic tracts, where the center of a new insurgent pulmonary lesion was seen. It could be an early alert radiological sign to predict initial lung deterioration. Another uncommon element was the presence of mediastinal lymphadenopathy with short-axis oval nodes. Conclusions Although only two patients have been studied, these findings are consistent with the radiological pattern described in literature. Finally, the pulmonary vessels enlargement in areas where new lung infiltrates develop in the follow-up CT scan, could describe an early predictor radiological sign of lung impairment.",2020,"Albarello, Fabrizio; Pianura, Elisa; Di Stefano, Federica; Cristofaro, Massimo; Petrone, Ada; Marchioni, Luisa; Palazzolo, Claudia; Schininà, Vincenzo; Nicastri, Emanuele; Petrosillo, Nicola; Campioni, Paolo; Petersen, Eskild; Zumla, Alimuddin; Ippolito, Giuseppe",International Journal of Infectious Diseases,2087800735,#2446,
,CZI,"Is the Africa prepared for tackling the COVID-19 (SARS-CoV-2) epidemic? - lessons from past outbreaks, ongoing pan-African public health efforts, and implications for the future",10.1016/j.ijid.2020.02.049,,,,,2020,"Kapata, Nathan; Ihekweazu, Chikwe; Ntoumi, Francine; Tajudeen, Raji; Chanda-Kapata, Pascalina; Mwaba, Peter; Mukonka, Victor; Bates, Matthew; Tembo, John; Corman, Victor; Mfinanga, Sayoki; Asogun, Danny; Elton, Linzy; Arruda, Liã Bárbara; Thomason, Margaret J.; Mboera, Leonard; Yavlinsky, Alexei; Haider, Najmul; Simons, David; Hollmann, Lara; Lule, Swaib A.; Veas, Francisco; Abdel Hamid, Muzamil Mahdi; Dar, Osman; Edwards, Sarah; Vairo, Francesco; McHugh, Timothy D.; Drosten, Christian; Kock, Richard; Ippolito, Giuseppe; Zumla, Alimuddin",International Journal of Infectious Diseases,3006645647,#2857,
,CZI,Recurrence of positive SARS-CoV-2 RNA in COVID-19: A case report,10.1016/j.ijid.2020.03.003,,,,"The ongoing outbreak of COVID-19 that began in Wuhan, China, has constituted a Public Health Emergency of International Concern, with cases confirmed in multiple countries. Currently patients are the main source of infection. We report a confirmed case of COVID-19 whose oropharyngeal swab test of SARS-CoV-2 RNA turned positive in convalescence. This case highlights the importance of dynamic surveillance of SARS-CoV-2 RNA for infectivity assessment.",2020,"Chen, Dabiao; Xu, Wenxiong; Lei, Ziying; Huang, Zhanlian; Liu, Jing; Gao, Zhiliang; Peng, Liang",International Journal of Infectious Diseases,3006645647,#4608,
,CZI,New regulatory strategies to manage medicines shortages in Europe,10.1016/j.ijpharm.2020.119171,,,,"Medicine shortages have been spreading in European countries. In many cases, the unavailability of medicinal products has a substantial impact on the capability of National Healthcare Systems in ensuring the continuity of care. Shortages originate from multifactorial causes. In particular, they can be due to supply-related factors (e.g., manufacturing issues, regulatory issues, logistics, distribution) and demand-related ones (e.g., fluctuating drug demand, parallel market, tendering, price and reimbursement policies). However, some extraordinary geopolitical events (e.g., Brexit) may also affect medicines’ availability. The capability of European Regulatory Authorities and other stakeholders, which are involved in the pharmaceutical distribution chain and the healthcare assistance services, to define suitable problem-solving strategies has been limited for years by the fragmentation of the European regulatory framework, starting from the lack of a univocal definition of a medicine shortage. Only in 2019, the EMA and HMA joint task force released the first harmonized “shortage” definition in the European Economic Area (EEA) and guidance on public communication. This manuscript aims to review the current European regulatory framework on medicine shortages. To support the activities of regulators, manufacturers and other healthcare professionals, an algorithm was also proposed to be used as a harmonized procedure to determine the shortage/unavailability impact on public health and to rationalize the problem-solving strategies adopted in all different settings.",2020,"Musazzi, Umberto M.; Di Giorgio, Domenico; Minghetti, Paola",International Journal of Pharmaceutics,2942764320,#3143,
,CZI,World Health Organization declares Global Emergency: A review of the 2019 Novel Coronavirus (COVID-19),10.1016/j.ijsu.2020.02.034,,,,"An unprecedented outbreak of pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December of 2019. A novel coronavirus was identified as the causative agent and was subsequently termed COVID-19 by the World Health Organization (WHO). Considered a relative of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), COVID-19 is a betacoronavirus that affects the lower respiratory tract and manifests as pneumonia in humans. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with 50,580 laboratory-confirmed cases and 1,526 deaths worldwide. In response to this global outbreak, we summarise the current state of knowledge surrounding COVID-19.",2020,"Sohrabi, Catrin; Alsafi, Zaid; O’Neill, Niamh; Khan, Mehdi; Kerwan, Ahmed; Al-Jabir, Ahmed; Iosifidis, Christos; Agha, Riaz",International Journal of Surgery,2965809604,#2395,
,CZI,Tuberculosis and novel Wuhan coronavirus infection: pathological interrelationship,10.1016/j.ijtb.2020.02.004,,,,,2020,"Yasri, Sora; Wiwanitkit, Viroj",Indian Journal of Tuberculosis,1932726324,#2084,
,CZI,What are we doing in the dermatology outpatient department amidst the raging of 2019-nCoV?,10.1016/j.jaad.2020.02.030,,,,,2020,"Chen, Yusha; Pradhan, Sushmita; Xue, Siliang",Journal of the American Academy of Dermatology,3006436003,#1156,
,CZI,Letter from the Editor,10.1016/j.jaad.2020.02.031,,,,,2020,"Elston, Dirk M.",Journal of the American Academy of Dermatology,2963953047,#983,
,CZI,Coronavirus (COVID-19) Outbreak: What the Department of Radiology Should Know,10.1016/j.jacr.2020.02.008,,32092296,,"In December 2019, a novel coronavirus (COVID-19) pneumonia emerged in Wuhan, China. Since then, this highly contagious COVID-19 has been spreading worldwide, with a rapid rise in the number of deaths. Novel COVID-19-infected pneumonia (NCIP) is characterized by fever, fatigue, dry cough, and dyspnea. A variety of chest imaging features have been reported, similar to those found in other types of COVID-19 syndromes. The purpose of the present review is to briefly discuss the known epidemiology and the imaging findings of COVID-19 syndromes, with a focus on the reported imaging findings of NCIP. Moreover, the authors review precautions and safety measures for radiology department personnel to manage patients with known or suspected NCIP. Implementation of a robust plan in the radiology department is required to prevent further transmission of the virus to patients and department staff members.",2020,"Kooraki, Soheil; Hosseiny, Melina; Myers, Lee; Gholamrezanezhad, Ali",Journal of the American College of Radiology : JACR,3005943294,#3714,
,CZI,Psychological intervention in oral patients in novel coronavirus pneumonia outbreak period,10.1016/j.jamda.2007.10.003,,,,"Public health emergencies have an impact on the public mental health. The outbreak of the novel coronavirus has affected the normal diagnosis and treatment services in oral medical institutions across the country. Delay of non-emergency dental service will have a potential impact on the experience, cognition, treatment and rehabilitation of patients with oral diseases. Through literature review, this paper reviewed the oral psychosomatic diseases closely related to patients' psychological state, such as oral mucosal disease, temporomandibular joint disease, bruxism, periodontal disease and so on. It was believed that these patients might be more susceptible to the impact of stress events, and dental specialists should pay more attention to them. At the same time, this paper analyzes the possible psychological stress symptoms of patients with different oral diseases, and puts forward suggestions for remote consultation and emergency treatment of dentists. From the perspective of social role, dentists not only played the role of expert in dental home professional guidance, but also played the role of psychological counseling for patients.",2020,"QU, Xing; ZHOU, Xue Dong",Chinese Journal of Stomatology,1991886054,#1941,
,CZI,Coronaphobia: Fear and the 2019-nCoV Outbreak,10.1016/j.janxdis.2020.102196,,,,,2020,"Asmundson, Gordon J. G.; Taylor, Steven",Journal of Anxiety Disorders,3005195331,#629,
,CZI,The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak,10.1016/j.jaut.2020.102433,,,,"Coronavirus disease (COVID-19) is caused by SARS-COV2 and represents the causative agent of a potentially fatal disease that is of great global public health concern. Based on the large number of infected people that were exposed to the wet animal market in Wuhan City, China, it is suggested that this is likely the zoonotic origin of COVID-19. Person-to-person transmission of COVID-19 infection led to the isolation of patients that were subsequently administered a variety of treatments. Extensive measures to reduce person-to-person transmission of COVID-19 have been implemented to control the current outbreak. Special attention and efforts to protect or reduce transmission should be applied in susceptible populations including children, health care providers, and elderly people. In this review, we highlights the symptoms, epidemiology, transmission, pathogenesis, phylogenetic analysis and future directions to control the spread of this fatal disease.",2020,"Rothan, Hussin A.; Byrareddy, Siddappa N.",Journal of Autoimmunity,3006645647,#2415,
,CZI,The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China,10.1016/j.jaut.2020.102434,,,,"The 2019-nCoV is officially called SARS-CoV-2 and is the cause of the disease named COVID-19. This viral epidemic in China has led to the deaths of over 1800 people, mostly elderly or those with an underlying chronic disease or immunosuppressed state. This is the third serious Coronavirus outbreak in less than 20 years, following SARS in 2002–2003 and MERS in 2012. While human strains of Coronavirus are associated with about 15% of cases of the common cold, the SARS-CoV-2 may present with varying degrees of severity, from flu-like symptoms to death. It is currently believed that this deadly Coronavirus strain originated from wild animals at the Huanan market in Wuhan, a city in Hubei province. Bats, snakes and pangolins have been cited as potential carriers based on the sequence homology of CoV isolated from these animals and the viral nucleic acids of the virus isolated from SARS-CoV-2 infected patients. Extreme quarantine measures, including sealing off large cities, closing borders and confining people to their homes, were instituted in January 2020 to prevent spread of the virus, but by that time much of the damage had been done, as human-human transmission became evident. While these quarantine measures are necessary and have prevented a historical disaster along the lines of the Spanish flu, earlier recognition and earlier implementation of quarantine measures may have been even more effective. Lessons learned from SARS resulted in faster determination of the nucleic acid sequence and a more robust quarantine strategy. However, it is clear that finding an effective antiviral and developing a vaccine are still significant challenges. The costs of the epidemic are not limited to medical aspects, as the virus has led to significant sociological, psychological and economic effects globally. Unfortunately, emergence of SARS-CoV-2 has led to numerous reports of Asians being subjected to racist behavior and hate crimes across the world.",2020,"Yang, Yongshi; Peng, Fujun; Wang, Runsheng; Guan, Kai; Jiang, Taijiao; Xu, Guogang; Sun, Jinlyu; Chang, Christopher",Journal of Autoimmunity,2999409984,#4387,
,CZI,"Rapid random access detection of the novel SARS-coronavirus-2 (SARS-CoV-2, previously 2019-nCoV) using an open access protocol for the Panther Fusion",10.1016/j.jcv.2020.104305,,,,,2020,"Cordes, Anne K.; Heim, Albert",Journal of Clinical Virology,1982149511,#2656,
,CZI,2019-novel coronavirus outbreak: A new challenge,10.1016/j.jgar.2020.02.021,,,,"Objectives Following the public health emergency declared by the World Health Organization and the recent outbreak by 2019-nCoV in China and through other 29 countries, we aimed to summarize the clinical aspects of novel beta-coronavirus infection and its possible clinical presentations together with suggested therapeutic algorithms for patients who may require antibiotic treatment. Methods We reviewed the currently available literature of microbiologically confirmed infections by 2019-ConV (or COVID-19) occurred at the time of writing (13 February 2020). A literature search was performed using the PubMed database and the Cochrane library. Search terms included ""novel coronavirus"" or ""2019-nCoV"" or “COVID-19”. Results Published cases occurred mostly in males (age ranged from 8 to 92). Cardiovascular, digestive and endocrine system diseases were commonly reported, except previous chronic pulmonary diseases (e.g., COPD, asthma, bronchiectasis) that were surprisingly underreported. Fever was presented in all the case series available, flanked by cough, dyspnea, myalgias and fatigue. Multiple bilateral lobular and subsegmental areas of consolidation or bilateral ground-glass opacities were the main reported radiological features of 2019-nCoV, at least in the early phases of disease. Conclusions The new 2019-nCoV epidemics is mainly associated with respiratory disease and few extrapulmonary signs. However, there is a low rate of associated pre-existing respiratory comorbidities.",2020,"Lupia, Tommaso; Scabini, Silvia; Pinna, Simone Mornese; Di Perri, Giovanni; De Rosa, Francesco Giuseppe; Corcione, Silvia",Journal of Global Antimicrobial Resistance,3003218364,#5473,
,CZI,Identification of potential cross-protective epitope between 2019-nCoV and SARS virus,10.1016/j.jgg.2020.01.003,,,,,2020,"Qiu, Tianyi; Mao, Tiantian; Wang, Yuan; Zhou, Mengdi; Qiu, Jingxuan; Wang, Jianwei; Xu, Jianqing; Cao, Zhiwei",Journal of Genetics and Genomics,3004310457,#121,
,CZI,Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines,10.1016/j.jgg.2020.02.001,,,,,2020,"Liu, Xin; Wang, Xiu-Jie",Journal of Genetics and Genomics,3006049090,#757,
,CZI,Preparedness and proactive infection control measures against the emerging novel coronavirus in China,10.1016/j.jhin.2020.01.010,,,,,2020,"Cheng, V. C. C.; Wong, S. C.; To, K. K. W.; Ho, P. L.; Yuen, K. Y.",Journal of Hospital Infection,3000694338,#3198,
,CZI,Novel coronavirus is putting the whole world on alert,10.1016/j.jhin.2020.01.019,,,,,2020,"Khan, S.; Ali, A.; Siddique, R.; Nabi, G.",Journal of Hospital Infection,3005427413,#226,
,CZI,Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents,10.1016/j.jhin.2020.01.022,,,,"Summary Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62–71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05–0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.",2020,"Kampf, G.; Todt, D.; Pfaender, S.; Steinmann, E.",Journal of Hospital Infection,3005057892,#3162,
,CZI,"Novel coronavirus, poor quarantine, and the risk of pandemic",10.1016/j.jhin.2020.02.002,,,,,2020,"Khan, S.; Siddique, R.; Ali, A.; Xue, M.; Nabi, G.",Journal of Hospital Infection,3005588847,#763,
,CZI,Novel coronavirus pneumonia emergency in Zhuhai: impact and challenges,10.1016/j.jhin.2020.02.005,,,,,2020,"Jin, Hao; Lu, Ligong; Liu, Junwei; Cui, Min",Journal of Hospital Infection,3006132735,#966,
,CZI,The non-contact handheld cutaneous infra-red thermometer for fever screening during the COVID-19 global emergency,10.1016/j.jhin.2020.02.010,,,,,2020,"Aw, Dr Junjie",Journal of Hospital Infection,2319752646,#1700,
,CZI,Journal of Hospital Infection to move to Article-Based Publishing,10.1016/j.jhin.2020.02.013,,,,,2020,,Journal of Hospital Infection,2886249692,#3225,
,CZI,COVID-19 in medical personnel: observation from Thailand,10.1016/j.jhin.2020.02.016,,32114054,,,2020,"Joob, Beuy; Wiwanitkit, Viroj",J Hosp Infect,2403835304,#3061,
,CZI,Integrated infection control strategy to minimize nosocomial infection of corona virus disease 2019 among ENT healthcare workers,10.1016/j.jhin.2020.02.018,,,,,2020,"Lu, Dan; Wang, Haiyang; Yu, Rong; HuiYang; Zhao, Yu",Journal of Hospital Infection,2010285947,#2893,
,CZI,"Practical experiences and suggestions on the eagle-eyed observer, a novel promising role for controlling nosocomial infection of the COVID-19 outbreak",10.1016/j.jhin.2020.02.020,,,,,2020,"Peng, Jianhui; Ren, Nina; Wang, Mingke; Zhang, Gangqing",Journal of Hospital Infection,2093686886,#4477,
,CZI,Association between 2019-nCoV transmission and N95 respirator use,10.1016/j.jhin.2020.02.021,,,,,2020,"Wang, Xinghuan; Pan, Zhenyu; Cheng, Zhenshun",Journal of Hospital Infection,3004826757,#4417,
,CZI,Effective strategies to prevent coronavirus disease-2019 (COVID-19) outbreak in hospital,10.1016/j.jhin.2020.02.022,,,,,2020,"Lee, Ing-Kit; Wang, Chih-Chi; Lin, Meng-Chih; Kung, Chia-Te; Lan, Kuo-Chung; Lee, Chien-Te",Journal of Hospital Infection,3005657121,#4526,
,CZI,Understanding the emerging coronavirus: what it means for health security and infection prevention,10.1016/j.jhin.2020.02.023,,,,,2020,"Peters, Alexandra; Vetter, Pauline; Guitart, Chloé; Lotfinejad, Nasim; Pittet, Didier",Journal of Hospital Infection,2079438251,#4475,
,CZI,Diagnosis of SARS-CoV-2 Infection based on CT scan vs. RT-PCR: Reflecting on Experience from MERS-CoV,10.1016/j.jhin.2020.03.001,,,,,2020,"Al-Tawfiq, Jaffar A.; Memish, Ziad A.",Journal of Hospital Infection,2168296380,#4635,
,CZI,Exploring the reasons for healthcare workers infected with novel coronavirus disease 2019 (COVID-19) in China,10.1016/j.jhin.2020.03.002,,,,,2020,"Wang, Jiancong; Zhou, Mouqing; Liu, Fangfei",Journal of Hospital Infection,3001118548,#4420,
,CZI,Duration of quarantine in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a question needing an answer,10.1016/j.jhin.2020.03.003,,,,"In December 2019 a new form of pneumonia was observed in the Chinese province of Hubei.[1] The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was subsequently identified as responsible of this condition, defined coronavirus disease (COVID-19).[2] The virus has now spread outside Chinese borders with 82,297 cases and 2,804 deaths worldwide at the 26th of February.[3] After infection, symptoms appear after an incubation time of 3-5 days, with 80% of those infected developing a mild disease, 15% a severe disease and 5% will require support in intensive care unit (ICU).[4] Overall, the estimated case-fatality rate is comprised between 0.4% and 2.9% and the basic reproduction number is approximately 3.28.[4,5] SARS-CoV-2 is a new pathogen for humankind and any type of immune protection exist, thus everybody can be potentially infected. Moreover, no primary prophylaxis measures (vaccination) nor effective treatments are available. If the above represented percentages are applied to the worldwide populations, it appears clear why any measure should be considered to avoid a further diffusion of the virus and prevent the saturation and collapse of health systems and the most catastrophic pandemic since 1919 Spanish flu. Isolation of those affected and the use of personal protective equipment (PPE) are the mainstay to block transmission of this pathogen, which is presumed through respiratory droplets. A 14 days quarantine is applied to subjects coming from endemic areas or who had contact with confirmed cases. It is assumed that, if in this period the subject does not develop any sign or symptoms compatible with COVID-19, he is not infected and thus the quarantine can be removed, and the subject returned to the community. Domiciliary quarantine of 14 days since a positive test is applied also for patients with a diagnosed mild disease who did not need medical support. These rules are effective in controlling infections in the community, but several doubts arise when it is necessary to transpose them in the hospital setting. Hospitals are indeed a delicate place in epidemics: they collect fragile persons who can be exposed to the virus and are subsequently readmitted to the community thus spreading the infection. Indeed, the ongoing outbreak in Northern Italy has been linked to a single infected patient who accessed to a community hospital where he transmitted the virus to several other patients and health-care operators.[6] Moreover, the isolation of patients in the hospital setting impose a significant burden in terms of PPE used by the health-care operators, space dedicated and time employed in their management. Even more complex is the situation of patients in ICU, where viral spreading is facilitated by endotracheal tubes and manoeuvres performed on the respiratory tract. Therefore, a clear definition of the infectiousness timing and intensity of viral spreading is mandatory to alleviate the burden on the health-care system. Unfortunately, the data available on the topic are scarce and composed only of measurements of viral shedding, without an assessment of the infectivity. Kim et al.[7] assessed the viral load kinetics of SARS-CoV-2 in upper and lower respiratory tract materials in the first two confirmed patients in Korea. They employed real-time reverse transcriptase polymerase chain reaction (rRT-PCR) to detect SARS-CoV-2 and converted cycle threshold (CT) values of rRT-PCR into RNA copy number. The detection limit of rRT-PCR was 2,690 copies/mL. Overall, viral load above detection limit was detected until 14 and 25 days after symptoms onset and for 13 and 11 days after the first detection, respectively.[7] Of note, both patients received treatment with lopinavir/ritonavir. Instead, Zou and colleagues analysed viral load in repeated nasal and throat swabs obtained from the 17 symptomatic patients.[8] They also employed rRT-PCR and considered a CT of 40 as detection limit. Higher viral loads were observed in nasal swabs and in samples collected soon after symptoms onset. Overall, only two patients prese ted positive samples, and only in nasal swab, 14 days after symptoms onset, and with low viral load. In conclusion, a larger amount of data about duration of viral spreading and infectivity in hospitalized patients, especially in ICU, is badly needed to better define quarantine period and avoid nosocomial transmission. Before their availability, the canonical 14 days period of quarantine should be respected.",2020,"Lombardi, Andrea; Bozzi, Giorgio; Mangioni, Davide; Muscatello, Antonio; Peri, Anna Maria; Taramasso, Lucia; Ungaro, Riccardo; Bandera, Alessandra; Gori, Andrea",Journal of Hospital Infection,3005788786,#5464,
,CZI,"Emergence of a novel coronavirus causing respiratory illness from Wuhan, China",10.1016/j.jinf.2020.01.014,,,,,2020,"Tang, Julian W.; Tambyah, Paul A.; Hui, David S.C.",Journal of Infection,3003843886,#39,
,CZI,Genetic diversity and potential recombination between ferret coronaviruses from European and American lineages,10.1016/j.jinf.2020.01.016,,,,,2020,"Xu, Yifei",Journal of Infection,3005204082,#2098,
,CZI,Emergence of SARS-like Coronavirus poses new challenge in China,10.1016/j.jinf.2020.01.017,,,,,2020,"Wang, Ruichen; Zhang, Xu; Irwin, David M.; Shen, Yongyi",Journal of Infection,3003671106,#45,
,CZI,The continuous evolution and dissemination of 2019 novel human coronavirus,10.1016/j.jinf.2020.02.001,,,,,2020,"Zhang, Jiahao; Ma, Kaixiong; Li, Huanan; Liao, Ming; Qi, Wenbao",Journal of Infection,3003886061,#1434,
,CZI,Novel coronavirus (2019-nCoV) cases in Hong Kong and implications for further spread,10.1016/j.jinf.2020.02.002,,,,,2020,"Kwok, Kin On; Wong, Valerie; Wei, Vivian Wan In; Wong, Samuel Yeung Shan; Tang, Julian Wei-Tze",Journal of Infection,3006078464,#1599,
,CZI,Clinical Features of Atypical 2019 Novel Coronavirus Pneumonia with an initially Negative RT-PCR Assay,10.1016/j.jinf.2020.02.008,,,,,2020,"Hao, Wendong",Journal of Infection,3005656138,#1633,
,CZI,Recent insights into 2019-nCoV: a brief but comprehensive review,10.1016/j.jinf.2020.02.010,,,,"A novel coronavirus designated as 2019-nCoV hit the central Chinese city of Wuhan in late December 2019, and subsequently spread rapidly to all provinces of China and multiple countries. Up to 0:00 am February 9, 2020, a total of 37,287 cases have been confirmed infection of 2019-nCoV in China mainland, and 302 cases have also been cumulatively reported from 24 countries. According to the latest data, a total of 813 deaths occurred in China mainland, with the mortality reaching approximately 2.2%. At present, there is no vaccine or specific drugs for human coronavirus, so that it's critical to understand the nature of the virus and its clinical characteristics to response to the 2019-nCoV outbreak. Thus, we summarize the not much but timely reports on the 2019-nCoV in the present study, briefly but comprehensively.",2020,"Han, Qingmei; Lin, Qingqing; Jin, Shenhe; You, Liangshun",Journal of Infection,2978182211,#1986,
,CZI,Chinese medical personnel against the 2019-nCoV,10.1016/j.jinf.2020.02.011,,,,,2020,"Feng, Zhan-hui; Cheng, Yong-ran; Chen, Juan; Ye, Lan; Zhou, Meng-Yun; Wang, Ming-Wei",Journal of Infection,2414960577,#1646,
,CZI,Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV,10.1016/j.jinf.2020.02.013,,,,,2020,"Li, Rui; Qiao, Songlin; Zhang, Gaiping",Journal of Infection,2082231154,#1584,
,CZI,Trend and forecasting of the COVID-19 outbreak in China,10.1016/j.jinf.2020.02.014,,,,,,"Li, Qiang; Feng, Wei; Quan, Ying-Hui",Journal of Infection,3005902168,#2988,
,CZI,"Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19):A multi-center study in Wenzhou city, Zhejiang, China",10.1016/j.jinf.2020.02.016,,,,"Background Little is known about COVID-19 outside Hubei. The aim of this paper was to describe the clinical characteristics and imaging manifestations of hospitalized patients with confirmed COVID-19 infection in Wenzhou, Zhejiang, China. Methods In this retrospective cohort study, 149 RT-PCR confirmed positive patients were consecutively enrolled from January 17th to February 10th, 2020 in three tertiary hospitals of Wenzhou. Outcomes were followed up until Feb 15th, 2020. Findings A total of 85 patients had Hubei travel/residence history, while another 49 had contact with people from Hubei and 15 had no traceable exposure history to Hubei. Fever, cough and expectoration were the most common symptoms, 14 patients had decreased oxygen saturation, 33 had leukopenia, 53 had lymphopenia, and 82 had elevated C reactive protein. On chest computed tomography, lung segments 6 and 10 were mostly involved. A total of 287 segments presented ground glass opacity, 637 presented mixed opacity and 170 presented consolidation. Lesions were more localized in the peripheral lung with a patchy form. No significant difference was found between patients with or without Hubei exposure history. Seventeen patients had normal CT on admission of these, 12 had negative findings even10 days later. Interpretation Most patients presented with a mild infection in our study. The imaging pattern of multifocal peripheral ground glass or mixed opacity with predominance in the lower lung is highly suspicious of COVID-19 in the first week of disease onset. Nevetheless, some patients can present with a normal chest finding despite testing positive for COVID-19. Funding: We did not receive any fundings.",2020,"Yang, Wenjie; Cao, Qiqi; Qin, Le; Wang, Xiaoyang; Cheng, Zenghui; Pan, Ashan; Dai, Jianyi; Sun, Qingfeng; Zhao, Fengquan; Qu, Jieming; Yan, Fuhua",Journal of Infection,3005477624,#2089,
,CZI,Characteristics of COVID-19 infection in Beijing,10.1016/j.jinf.2020.02.018,,,,"Background : Since the first case of a novel coronavirus (COVID-19) infection pneumonia was detected in Wuhan, China, a series of confirmed cases of the COVID-19 were found in Beijing. We analyzed the data of 262 confirmed cases to determine the clinical and epidemiological characteristics of COVID-19 in Beijing. Methods : We collected patients who were transferred by Beijing Emergency Medical Sevice to the designated hospitals. The information on demographic, epidemiological, clinical, laboratory test for the COVID-19 virus, diagnostic classification, cluster case and outcome were obtained. Furthermore we compared the characteristics between severe and common confirmed cases which including mild cases, no-pneumonia cases and asymptomatic cases, and we also compared the features between COVID-19 and 2003 SARS. Findings : By Feb 10, 2020, 262 patients were transferred from the hospitals across Beijing to the designated hospitals for special treatment of the COVID-19 infected by Beijing emergency medical service. Among of 262 patients, 46 (17.6%) were severe cases, 216 (82.4%) were common cases, which including 192 (73.3%) mild cases, 11(4.2%) non-pneumonia cases and 13 (5.0%) asymptomatic cases respectively. The median age of patients was 47.5 years old and 48.5% were male. 192 (73.3%) patients were residents of Beijing, 50 (26.0%) of which had been to Wuhan, 116 (60.4%) had close contact with confirmed cases, 21 (10.9%) had no contact history. The most common symptoms at the onset of illness were fever (82.1%), cough (45.8%), fatigue (26.3%), dyspnea (6.9%) and headache (6.5%). The median incubation period was 6.7 days, the interval time from between illness onset and seeing a doctor was 4.5 days. As of Feb 10, 17.2% patients have discharged and 81.7% patients remain in hospital in our study, the fatality of COVID-19 infection in Beijing was 0.9%. Interpretation : On the basis of this study, we provided the ratio of the COVID-19 infection on the severe cases to the mild, asymptomatic and non-pneumonia cases in Beijing. Population was generally susceptible, and with a relatively low fatality rate. The measures to prevent transmission was very successful at early stage, the next steps on the COVID-19 infection should be focused on early isolation of patients and quarantine for close contacts in families and communities in Beijing. Funding Beijing Municipal Science and Technology Commission and Ministry of Science and Technology.",2020,"Tian, Sijia; Hu, Nan; Lou, Jing; Chen, Kun; Kang, Xuqin; Xiang, Zhenjun; Chen, Hui; Wang, Dali; Liu, Ning; Liu, Dong; Chen, Gang; Zhang, Yongliang; Li, Dou; Li, Jianren; Lian, Huixin; Niu, Shengmei; Zhang, Luxi; Zhang, Jinjun",Journal of Infection,3005679569,#2148,
,CZI,Simulating and Forecasting the Cumulative Confirmed Cases of SARS-CoV-2 in China by Boltzmann Function-based Regression Analyses,10.1016/j.jinf.2020.02.019,,,,,2020,"Fu, Xinmiao; Ying, Qi; Zeng, Tieyong; Long, Tao; Wang, Yan",Journal of Infection,3006355661,#1993,
,CZI,Novel coronavirus disease (Covid-19): the first two patients in the UK with person to person transmission,10.1016/j.jinf.2020.02.020,,,,,2020,"Lillie, Patrick J.; Samson, Anda; Li, Ang; Adams, Kate; Capstick, Richard; Barlow, Gavin D.; Easom, Nicholas; Hamilton, Eve; Moss, Peter J.; Evans, Adam; Ivan, Monica; Team, P. H. E. Incident; Taha, Yusri; Duncan, Christopher J. A.; Schmid, Matthias L.",Journal of Infection,3006007867,#2881,
,CZI,Clinical and CT imaging features of 2019 novel coronavirus disease (COVID-19),10.1016/j.jinf.2020.02.022,,,,"Tang JW, et al. and colleagues have written to this Journal describing the emergence of 2019 novel coronavirus disease (COVID-19).1 We have had an opportunity to examine in detail the chest computed tomography (CT) findings in cases with microbiologically confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, to familiarize radiologists and clinicians with the imaging manifestations of this new outbreak. Meanwhile, we also studied the clinical characteristics of the cases, combined with CT manifestations, to provide more clues for the correct diagnosis of the disease. Six female patients (P1-P6) aged from 27 to 63 years were referred to the fever clinic of our hospital. None of the patients had underlying diseases such as diabetes, malignant tumour or respiratory disease. Among the 6 cases, 5 (P1-P5) had a history of exposure to Wuhan or Hubei, and P6 had no clear epidemiological history. All the patients performed oropharyngeal swabs test and confirmed as COVID-19. Common respiratory viruses, mycoplasma and chlamydia were negative. For patients’ venous blood tests at disease onset, as given in (Table 1), we found that leucocytes, lymphocytes and percentage were slightly decreased or normal, eosinophil count and percentage were slightly decreased in 4 cases and normal in 2 cases. Additionally, 4 days later, P1 reperformed the follow-up hematologic examination. Compared with the blood test at disease onset, the results showed that the eosinophil count was still below the normal range, which was even lower than the first time.",,"Zhu, Ying; Liu, Yang-Li; Li, Zi-Ping; Kuang, Jian-Yi; Li, Xiang-Min; Yang, You-You; Feng, Shi-Ting",Journal of Infection,3005929298,#3478,
,CZI,"Corona Virus Disease 2019, a growing threat to children?",10.1016/j.jinf.2020.02.024,,,,,,"Yang, Pu; Liu, Pin; Li, Dan; Zhao, Dongchi",Journal of Infection,3006645647,#3480,
,CZI,Insights into the cross-species evolution of 2019 novel coronavirus,10.1016/j.jinf.2020.02.025,,,,"Recent study reported in this journal that the threats of continuous evolution and dissemination of 2019 human coronaviruses.1 Since its emergence in December 2019, a “seventh” member of the family of 2019 human coronavirus named “SARS-CoV-2” was responsible for an outbreak of coronavirus disease (COVID-19) in Wuhan, China.2 As of February 23, 2020, China had reported more than 77,042 confirmed cases of SARS-CoV-2, with 2,445 fatalities and counting (http://www.nhc.gov.cn). Strikingly, SARS-CoV-2 had been transmitted rapidly in more than 29 countries to date (https://www.who.int), including Asia, Europe, North America, Africa, and Oceania, posing serious concerns about its pandemic potential. Despite of droplet and contact transmissions of SARS-CoV-2, recent studies demonstrated that SARS-CoV-2 might be transmitted via aerosol and fecal–oral routes 3 (Figure 1), which needs to be paid attention in particular.",,"Zhang, Jiahao; Jia, Weixin; Zhu, Junhai; Li, Bo; Xing, Jinchao; Liao, Ming; Qi, Wenbao",Journal of Infection,3003886061,#3479,
,CZI,Identification of the hyper-variable genomic hotspot for the novel coronavirus SARS-CoV-2,10.1016/j.jinf.2020.02.027,,,,"A recent study in this journal studied the genomes of the novel SARS-like coronavirus (SARS-CoV-2) in China and suggested that the SARS-CoV-2 had undergone genetic recombination with SARS-related CoV1. By February 14, 2020, a total of 66,576 confirmed cases of COVID-19, people infected with SARS-CoV-2, were reported in China, leading to 1,524 deaths, per the Chinese CDC (http://2019ncov.chinacdc.cn/2019-nCoV/). Several full genomic sequences of this virus have been released for the study of its evolutionary origin and molecular characteristics2, 3, 4. Here, we analyzed the potential mutations that may have evolved after the virus became epidemic among humans and also the mutations resulting in the human adaptation. The sequences of BetaCoV were downloaded on February 3, 2020 from the GISAID platform5. A total of 58 accessions were available, among which BetaCoV/bat/Yunnan/RaTG13/2013 is a known close relative of SARS-CoV-2. Four accessions, namely, BetaCov/Italy/INM1/2020, BetaCov/Italy/INM2/2020, BetaCoV/Kanagawa/1/2020, and BetaCoV/USA/IL1/2020, were excluded because of the short-truncated sequences or multiple ambiguous nucleotides. A total of 54 accessions (Supplementary table 1) isolated from humans were utilized in the following analysis. The sequences NC_004718.3 of SARS coronavirus6 genes were utilized to define the protein products of SARS-CoV-2. The protein sequences of ORF1ab, S, E, M, and N genes were translated, and all of the loci without experimental evidences were excluded. First, the protein sequences of SARS-CoV-2 were compared with RaTG13, human SARS (NC_004718.3), bat SARS (DQ022305.2), and human MERS (NC_019843.3) by calculating the similarity in a given sliding window (Figure 1A). The sliding window was set to 500 for ORF1ab and S, and to 50 for proteins E, M, and N considering their short length. SARS-CoV-2 were highly similar to RaTG13 isolated from bats, showing 96% identity based on the whole-nucleotide sequences and 83% based on the protein sequences, suggesting a bat zoonotic origin of SARS-CoV-2. ORF1a, and the head of S seemed to have diverged from other beta coronaviruses.",,"Wen, Feng; Yu, Hai; Guo, Jinyue; Li, Yong; Luo, Kaijian; Huang, Shujian",Journal of Infection,3005538648,#4195,
,CZI,Clinical manifestations and outcome of SARS-CoV-2 infection during pregnancy,10.1016/j.jinf.2020.02.028,,,,"Tang and colleagues, in this Journal, drew readers attention to emerging COVID19.1 We focused on the pregnant COVID19 patients. Given the maternal physiologic and immune function changes in pregnancy,2 pregnant individuals might face greater risk of getting infected by SARS-CoV-2 and might have more complicated clinical events. We described epidemiological, clinical characteristics, pregnancy and perinatal outcomes of all hospitalized pregnant patients diagnosed with COVID-19 in China. We identified all hospitalized pregnant patients with laboratory-confirmed SARS-CoV-2 infection between December 8, 2019, and February 25, 2020 officially reported by the central government, in areas outside Wuhan, China. Information including age, geographic location, epidemiological history, prenatal course, maternal and newborn hospital course, discharge data and outcome were obtained by Centers for Disease Control and Prevention and Local Health Commission. When necessary, we attempted to contact local hospital or patients by telephone to supply missing information. This investigation was part of an emergency public health outbreak investigation and therefore not subject to institutional review board. There were a total of 13 Chinese patients with SARS-CoV-2 admitted to hospitals outside of Wuhan (Table 1). There were 3 patients from Zhejiang, 3 from other cities of Hubei and 1 each from Fujian, Shanxi, Beijing, Guangdong, Jiangxi, Heilongjiang and Anhui. The maternal age ranged between 22 to 36 years. Two women were less than 28 weeks of gestation and the other 11 patients were in their third trimesters at presentation. None of the patients had underlying medical disease.",,"Liu, Yangli; Chen, Haihong; Tang, Kejing; Guo, Yubiao",Journal of Infection,2279386236,#3797,
,CZI,Lymphopenic community acquired pneumonia as signature of severe COVID-19 infection: Lymphopenia in severe COVID-19 infection,10.1016/j.jinf.2020.02.029,,,,"In two recent articles from Huang C et al and Yang X in The Lancet,2,3 85% of critically ill patients with COVID-19 showed lymphopenia. The presence of lymphopenia as a signature of severe COVID-19 was confirmed by Wang D et al, who, in their study published in JAMA, reported that ICU patients suffering this infection had a median lymphocyte count of 800 cells/mm,3 with non survivors exhibiting persistent lymphopenia.4 ICU patients present also with high levels of plasma cytokines.2 The existence of hyper-cytokinemia in COVID-19 patients with lymphopenia could indicate a poor control of the pathogen, as showed in severe patients infected with the 2009 Pandemic Influenza virus. Interestingly, hypercytokinemia and lymphopenia were also evident in critical patients with Severe Acute Respiratory Syndrome due to the Coronavirus emerged in 2003 (SARS-CoV).5,6 These features (lymphopenia + hypercytokinemia) fit the characteristics of a particular immunological phenotype of community acquired pneumonia (CAP), lymphopenic CAP (L-CAP), which, as we recently demonstrated in an article published in the Journal of Infection, is associated with increased severity, mortality and a dysregulated immunological response.7 In their works, Yang X et al and Chen N et al propose a direct cytotoxic action of the virus to explain the low lymphocyte counts observed in the severe cases of COVID-19.3,8 But, in our opinion, host factors could also contribute to induce lymphopenia in these cases. Compared with those patients not requiring intensive care, COVID-19 patients admitted to the ICU are older and are more likely to have hypertension, diabetes, cardiovascular and cerebrovascular disease.4 Aging and chronic diseases induce chronic endothelial dysfunction. As we recently reviewed in J Clin Med, endothelial dysfunction induces disassembly of intercellular junctions, endothelial cell death and blood-tissue barrier disruption, along with enhanced leukocyte adhesion and extravasation, which could contribute to explain the lymphopenia observed in severe COVID-19 patients.9 Recent findings from our group have evidenced the interconnection between lymphopenia and endothelial dysfunction in patients with CAP and organ failure.10 Endothelial dysfunction induces also increased oxidative stress and systemic inflammation, glycocalyx degradation and shedding along with a pro-coagulant and anti-fibrinolytic state.9 In aged individuals with chronic diseases, these features could represent predisposing factors for presenting a severe respiratory failure following COVID-19 infection.",,"Bermejo-Martin, Jesús F.; Almansa, Raquel; Menéndez, Rosario; Mendez, Raúl; Kelvin, David J.; Torres, Antoni",Journal of Infection,2953538649,#3547,
,CZI,Public health might be endangered by possible prolonged discharge of SARS-CoV-2 in stool,10.1016/j.jinf.2020.02.031,,,,"The published data, which showed the COVID-19 patients with low digestive?manifestation, might be misleading. Case with negative URT test showed positive in?rectal scarab which challenge the isolation protocol.?As fomite transmission caused clusters of infection of SARS, adequate disinfection?operations should be adopted in SARS-CoV-2 outbreak.",,"He, Yu; Wang, Zhengli; Li, Fang; Shi, Yuan",Journal of Infection,3006332573,#3634,
,CZI,Traditional chinese medicine is a resource for drug discovery against 2019 novel coronavirus (SARS-CoV-2),10.1016/j.joim.2020.02.004,,,,,2020,"Ling, Chang-quan",Journal of Integrative Medicine,2958029267,#1288,
,CZI,Molecular immune pathogenesis and diagnosis of COVID-19,10.1016/j.jpha.2020.03.001,,,,"Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia with an unusual outbreak in Wuhan, China, in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic coronavirus into the human population after the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) in the twenty-first century. In this minireview, we provide a brief introduction of the general features of SARS-CoV-2 and discuss current knowledge of molecular immune pathogenesis, diagnosis and treatment of COVID-19 on the base of the present understanding of SARS-CoV and MERS-CoV infections, which may be helpful in offering novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection.",2020,"Li, Xiaowei; Geng, Manman; Peng, Yizhao; Meng, Liesu; Lu, Shemin",Journal of Pharmaceutical Analysis,1601033402,#4519,
,CZI,Quantitative computed tomography analysis for stratifying the severity of Coronavirus Disease 2019,10.1016/j.jpha.2020.03.004,,,,"Purpose To examine the feasibility of using a computer tool for stratifying the severity of Coronavirus Disease 2019 (COVID-19) based on computed tomography (CT) images. Materials and methods We retrospectively examined 44 confirmed COVID-19 cases. All cases were evaluated separately by radiologists (visually) and through an in-house computer software. The degree of lesions was visually scored by the radiologist, as follows, for each of the 5 lung lobes: 0, no lesion present; 1, <1/3 involvement; 2, >1/3 and < 2/3 involvement; and 3, >2/3 involvement. Lesion density was assessed based on the proportion of ground-glass opacity (GGO), consolidation and fibrosis of the lesions. The parameters obtained using the computer tool included lung volume (mL), lesion volume (mL), lesion percentage (%), and mean lesion density (HU) of the whole lung, right lung, left lung, and each lobe. The scores obtained by the radiologists and quantitative results generated by the computer software were tested for correlation. A Chi-square test was used to test the consistency of radiologist- and computer-derived lesion percentage in the right/left lung, upper/lower lobe, and each of the 5 lobes. Result The results showed a strong to moderate correlation between lesion percentage scores obtained by radiologists and the computer software (r ranged from 0.7679 to 0.8373, P < 0.05), and a moderate correlation between the proportion of GGO and mean lesion density (r = −0.5894, P < 0.05), and proportion of consolidation and mean lesion density (r = 0.6282, P < 0.05). Computer-aided quantification showed a statistical significant higher lesion percentage for lower lobes than that assessed by the radiologists (χ2 = 8.160, P = 0.004). Conclusions Our experiments demonstrated that the computer tool could reliably and accurately assess the severity and distribution of pneumonia on CT scans.",2020,"Shen, Cong; Yu, Nan; Cai, Shubo; Zhou, Jie; Sheng, Jiexin; Liu, Kang; Zhou, Heping; Guo, Youmin; Niu, Gang",Journal of Pharmaceutical Analysis,2970191042,#4449,
,CZI,Management strategy of Novel coronavirus pneumonia in burn and wound care ward,10.1016/j.jpra.2018.04.003,,,,"The prevention and control of novel coronavirus pneumonia (NCP) has already entered a key period . The patients treated in the burn and wound care ward are susceptible to viral infection because of disease, age and other factors, so it is very important to manage the burn and wound care ward during the prevention and control of NCP epidemic. In this paper, combining with the key clinical problems of prevention and control in hospital during the epidemic period of NCP infection, medical evidence, and clinical and management experience, the author formulates prevention and control management strategy of the author's unit in order to provide reference for prevention and control of burn and wound care ward.",2020,"LI, Ning; LIU, Ting Min; CHEN, Hua Ling; LIAO, Jian Mei",Chinese Journal of Burns,2808056403,#1965,
,CZI,Pulmonary pathology of early phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer,10.1016/j.jtho.2020.02.010,,,,"There is currently a lack of pathologic data on the novel coronavirus (SARS-CoV-2) pneumonia, or COVID-19, from autopsy or biopsy. Two patients who recently underwent lung lobectomies for adenocarcinoma were retrospectively found to have had COVID-19 at the time of surgery. These two cases thus provide important first opportunities to study the pathology of COVID-19. Pathologic examinations revealed that, apart from the tumors, the lungs of both patients exhibited edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. Since both patients did not exhibit symptoms of pneumonia at the time of surgery, these changes likely represent an early phase of the lung pathology of COVID-19 pneumonia.",2020,"Tian, Sufang; Hu, Weidong; Niu, Li; Liu, Huan; Xu, Haibo; Xiao, Shu-Yuan",Journal of Thoracic Oncology,3005943294,#2529,
,CZI,"Editorial: Coronaviruses: Facts, Myths and Hypotheses",10.1016/j.jtho.2020.02.024,,,,"Abstract 26 There is currently a lack of pathologic data on the novel coronavirus (SARS-CoV-2) 27 pneumonia, or COVID-19, from autopsy or biopsy. Two patients who recently 28 underwent lung lobectomies for adenocarcinoma were retrospectively found to have had 29 COVID-19 at the time of surgery. These two cases thus provide important first 30 opportunities to study the pathology of COVID-19. Pathologic examinations revealed 31 that, apart from the tumors, the lungs of both patients exhibited edema, proteinaceous 32 exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular 33 infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. 34 Since both patients did not exhibit symptoms of pneumonia at the time of surgery, these 35 changes likely represent an early phase of the lung pathology of COVID-19 pneumonia. 36 37 Key words: coronavirus; COVID-19 pneumonia, pathology; SARS-CoV-2 38 39 40",2020,"Carbone, Michele; Green, Joshua B.; Bucci, Enrico M.; Lednicky, John J.",Journal of Thoracic Oncology,2077304999,#5094,
,CZI,The Treatment and Outcome of a Lung Cancer Patient Infected with SARS-CoV-2,10.1016/j.jtho.2020.02.025,,,,,2020,"Zhang, Hongyan; Huang, Yihua; Xie, Conghua",Journal of Thoracic Oncology,2044076874,#4377,
,CZI,Suggestions for thoracic surgery clinical practice in non-epidemic area of coronavirus infected disease-19,10.1016/j.jvs.2010.08.027,,,,"In this paper, the mechanism of destroying human alveolar epithelial cells and pulmonary tissue by 2019 novel coronavirus (2019-nCoV) was discussed firstly. There may be multiple mechanisms including killing directly the target cells and hyperinflammatory responses. Secondly, the clinical features, CT imaging, short-term and long-term pulmonary function damage of the 2019 novel coronavirus pneumonia (COVID-19) was analyzed. Finally, some suggestions for thoracic surgery clinical practice in non-epidemic area during and after the epidemic of COVID-19 was provided, to help all the thoracic surgery patients receive active and effective treatment.",2020,"DAI, Fuqiang; TAN, Qunyou",Chinese Journal of Surgery,2113129487,#2314,
,CZI,The Novel Coronavirus 2019 Epidemic and Kidneys,10.1016/j.kint.2020.03.001,,,,,2020,"Naicker, Saraladevi; Yang, Chih-Wei; Hwang, Shang-Jyh; Liu, Bi-Cheng; Chen, Jiang-Hua; Jha, Vivekanand",Kidney International,3005643121,#4918,
,CZI,"Anti-HCV, nucleotide inhibitors, repurposing against COVID-19",10.1016/j.lfs.2020.117477,,,,"Aims A newly emerged Human Coronavirus (HCoV) is reported two months ago in Wuhan, China (COVID-19). Until today >2700 deaths from the 80,000 confirmed cases reported mainly in China and 40 other countries. Human to human transmission is confirmed for COVID-19 by China a month ago. Based on the World Health Organization (WHO) reports, SARS HCoV is responsible for >8000 cases with confirmed 774 deaths. Additionally, MERS HCoV is responsible for 858 deaths out of about 2500 reported cases. The current study aims to test anti-HCV drugs against COVID-19 RNA dependent RNA polymerase (RdRp). Materials and methods In this study, sequence analysis, modeling, and docking are used to build a model for Wuhan COVID-19 RdRp. Additionally, the newly emerged Wuhan HCoV RdRp model is targeted by anti-polymerase drugs, including the approved drugs Sofosbuvir and Ribavirin. Key findings The results suggest the effectiveness of Sofosbuvir, IDX-184, Ribavirin, and Remidisvir as potent drugs against the newly emerged HCoV disease. Significance The present study presents a perfect model for COVID-19 RdRp enabling its testing in silico against anti-polymerase drugs. Besides, the study presents some drugs that previously proved its efficiency against the newly emerged viral infection.",2020,"Elfiky, Abdo A.",Life Sciences,1174154477,#2799,
,CZI,Guide to Understanding the 2019 Novel Coronavirus,10.1016/j.mayocp.2020.02.003,,,,,2020,"Shah, Aditya; Kashyap, Rahul; Tosh, Pritish; Sampathkumar, Priya; O’Horo, John C.",Mayo Clinic Proceedings,3003790823,#2933,
,CZI,"One world, one health: The novel coronavirus COVID-19 epidemic",10.1016/j.medcli.2020.02.002,,32093921,,,2020,"Trilla, Antoni",Med Clin (Barc),3005802710,#1924,
,CZI,Novel coronavirus: From discovery to clinical diagnostics,10.1016/j.meegid.2020.104211,,,,"A novel coronavirus designated as 2019-nCoV first appeared in Wuhan, China in late December 2019. Dozens of people died in China, and thousands of people infected as 2019-nCoV continues to spread around the world. We have described the discovery, emergence, genomic characteristics, and clinical diagnostics of 2019-nCoV.",2020,"Phan, Tung","Infection, Genetics and Evolution",3004202398,#108,
,CZI,Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event,10.1016/j.meegid.2020.104212,,,,"Background A novel coronavirus (2019-nCoV) associated with human to human transmission and severe human infection has been recently reported from the city of Wuhan in China. Our objectives were to characterize the genetic relationships of the 2019-nCoV and to search for putative recombination within the subgenus of sarbecovirus. Methods Putative recombination was investigated by RDP4 and Simplot v3.5.1 and discordant phylogenetic clustering in individual genomic fragments was confirmed by phylogenetic analysis using maximum likelihood and Bayesian methods. Results Our analysis suggests that the 2019-nCoV although closely related to BatCoV RaTG13 sequence throughout the genome (sequence similarity 96.3%), shows discordant clustering with the Bat_SARS-like coronavirus sequences. Specifically, in the 5′-part spanning the first 11,498 nucleotides and the last 3′-part spanning 24,341–30,696 positions, 2019-nCoV and RaTG13 formed a single cluster with Bat_SARS-like coronavirus sequences, whereas in the middle region spanning the 3′-end of ORF1a, the ORF1b and almost half of the spike regions, 2019-nCoV and RaTG13 grouped in a separate distant lineage within the sarbecovirus branch. Conclusions The levels of genetic similarity between the 2019-nCoV and RaTG13 suggest that the latter does not provide the exact variant that caused the outbreak in humans, but the hypothesis that 2019-nCoV has originated from bats is very likely. We show evidence that the novel coronavirus (2019-nCov) is not-mosaic consisting in almost half of its genome of a distinct lineage within the betacoronavirus. These genomic features and their potential association with virus characteristics and virulence in humans need further attention.",2020,"Paraskevis, D.; Kostaki, E.G.; Magiorkinis, G.; Panayiotakopoulos, G.; Sourvinos, G.; Tsiodras, S.","Infection, Genetics and Evolution",3003223635,#41,
,CZI,Genetic diversity and evolution of SARS-CoV-2,10.1016/j.meegid.2020.104260,,,,COVID-19 is a viral respiratory illness caused by a new coronavirus called SARS-CoV-2. The World Health Organization declared the SARS-CoV-2 outbreak a global public health emergency. We performed genetic analyses of eighty-six complete or near-complete genomes of SARS-CoV-2 and revealed many mutations and deletions on coding and non-coding regions. These observations provided evidence of the genetic diversity and rapid evolution of this novel coronavirus.,2020,"Phan, Tung","Infection, Genetics and Evolution",3006448444,#1522,
,CZI,"Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China",10.1016/j.micinf.2020.01.003,,,,"On 10 January 2020, a new coronavirus causing a pneumonia outbreak in Wuhan City in central China was denoted as 2019-nCoV by the World Health Organization (WHO). As of 24 January 2020, there were 887 confirmed cases of 2019-nCoV infection, including 26 deaths, reported in China and other countries. Therefore, combating this new virus and stopping the epidemic is a matter of urgency. Here, we focus on advances in research and development of fast diagnosis methods, as well as potential prophylactics and therapeutics to prevent or treat 2019-nCoV infection.",2020,"Yu, Fei; Du, Lanying; Ojcius, David M.; Pan, Chungen; Jiang, Shibo",Microbes and Infection,3003191692,#118,
,CZI,Mysterious infections in China: Novel coronavirus identified as cause of pneumonia,10.1016/j.micinf.2020.01.003,,,,,2020,,Deutsche Apotheker Zeitung,3003191692,#116,
,CZI,The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future,10.1016/j.micinf.2020.02.002,,,,"At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV.",2020,"Li, Jin-Yan; You, Zhi; Wang, Qiong; Zhou, Zhi-Jian; Qiu, Ye; Luo, Rui; Ge, Xing-Yi",Microbes and Infection,3004668429,#1384,
,CZI,Lessons learned from the 2019-nCoV epidemic on prevention of future infectious diseases,10.1016/j.micinf.2020.02.004,,,,"Only a month after the outbreak of pneumonia caused by 2019-nCoV, more than forty-thousand people were infected. This put enormous pressure on the Chinese government, medical healthcare provider, and the general public, but also made the international community deeply nervous. On the 25th day after the outbreak, the Chinese government implemented strict traffic restrictions on the area where the 2019-nCoV had originated—Hubei province, whose capital city is Wuhan. Ten days later, the rate of increase of cases in Hubei showed a significant difference (p = 0.0001) compared with the total rate of increase in other provinces of China. These preliminary data suggest the effectiveness of a traffic restriction policy for this pandemic thus far. At the same time, solid financial support and improved research ability, along with network communication technology, also greatly facilitated the application of epidemic prevention measures. These measures were motivated by the need to provide effective treatment of patients, and involved consultation with three major groups in policy formulation—public health experts, the government, and the general public. It was also aided by media and information technology, as well as international cooperation. This experience will provide China and other countries with valuable lessons for quickly coordinating and coping with future public health emergencies.",2020,"Pan, Xingchen; Ojcius, David M.; Gao, Tianyue; Li, Zhongsheng; Pan, Chunhua; Pan, Chungen",Microbes and Infection,2321034157,#1367,
,CZI,Is COVID-19 Receiving ADE From Other Coronaviruses?,10.1016/j.micinf.2020.02.006,,,,"One of the most perplexing questions regarding the current COVID-19 coronavirus epidemic is the discrepancy between the severity of cases observed in the Hubei province of China and those occurring elsewhere in the world. One possible answer is antibody dependent enhancement (ADE) of SARS-CoV-2 due to prior exposure to other coronaviruses. ADE modulates the immune response and can elicit sustained inflammation, lymphopenia, and/or cytokine storm, one or all of which have been documented in severe cases and deaths. ADE also requires prior exposure to similar antigenic epitopes, presumably circulating in local viruses, making it a possible explanation for the observed geographic limitation of severe cases and deaths.",2020,"Tetro, Jason A.",Microbes and Infection,3006338236,#1484,
,CZI,Internatioanl News Letter - April 2020,10.1016/j.midw.2020.102668,,,,,2020,"Duff, Elizabeth",Midwifery,2990427063,#4644,
,CZI,Effect of TLR agonist on infections bronchitis virus replication and cytokine expression in embryonated chicken eggs,10.1016/j.molimm.2020.02.001,,,,"Avian infectious bronchitis (IB) is an acute, highly infectious and contagious viral disease of chickens caused by avian infectious bronchitis virus (IBV) belonging to the genus Coronavirus and family Coronaviridae. It can affect all age groups of birds. The toll-like receptors (TLRs) are a major class of innate immune pattern recognition receptors that have a key role in immune response and defense against various infections.The TLRs are essential for initiation of innate immune responses and in the development of adaptive immune responses. An in ovo model was employed to study the antiviral activity of TLR ligands (Pam3CSK4, LPS and CpG ODN) on replication of IBV. It was hypothesized that optimum dose and specific timing of TLR ligands may reduce viral load of IBV in specific pathogen free (SPF) embryonated chicken eggs (ECEs). Further, the mechanism involved in the TLR-mediated antiviral response in chorioallantoic membrane (CAM) of ECEs was investigated. The ECEs of 9–11 days old were treated with different doses (high, intermediate and low) of TLR-2 (Pam3CSK4), TLR-4 (LPS) and TLR-21 (CpG ODN) ligands. In addition, to know the timing of TLR ligand treatment, six time intervals were analyzed viz. 36, 24 and 12 h prior to infection, time of infection (co-administration of TLR ligands and avian IBV) and 12 and 24 h post-IBV infection. For studying the relative expression of immuno-stimulatory genes (IFN-α, IFN-β, IFN-γ, IL-1β, iNOS and OAS) in CAM, TLR ligands were administered through intra-allantoicroute and CAM were collected at 4, 8 and 16 h post treatment. The results demonstrated that intermediate dose of all the three TLR ligands significantly reduced virus titers and used in the present study. However, the LPS reduced virus titer pre- and post-IBV infection but Pam3CSK4 and CpG ODN reduced only pre-IBV infection. Further analysis showed that TLR ligands induced IFN-γ, IL-1β and IFN stimulated genes viz. iNOS and OAS genes in CAM. The present study pointed towards the novel opportunities for rational design of LPS as immuno-stimulatory agent in chickens with reference to IBV. It may be speculated that in ovo administration of these TLR ligands may enhance resistance against viral infection in neonatal chicken and may contribute towards the development of more effective and safer vaccines including in ovo vaccines.",2020,"Sharma, Bal Krishan; Kakker, Naresh Kumar; Bhadouriya, Sakshi; Chhabra, Rajesh",Molecular Immunology,3006185830,#2404,
,CZI,"Novel Viruses, Zoonotic Infections, and Travel Health",10.1016/j.nwh.2020.02.002,,,,,2020,"Brucker, Mary C.",Nursing for Women's Health,1603291205,#1687,
,CZI,Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus,10.1016/j.pcad.2020.02.007,,,,,2020,"McCarty, Mark F.; DiNicolantonio, James J.",Progress in Cardiovascular Diseases,3005568099,#824,
,CZI,Traditional Chinese Medicine for COVID-19 Treatment,10.1016/j.phrs.2020.104743,,,,,2020,"Ren, Jun-ling; Zhang, Ai-Hua; Wang, Xi-Jun",Pharmacological Research,2998439854,#4461,
,CZI,"In bid to rapidly expand coronavirus testing, U.S. agency abruptly changes rules | Science | AAAS",10.1016/j.prevetmed.2015.10.018,,,,"The Food and Drug Administration (FDA) today recommended a dramatic shift in how it implements regulations that control whether laboratories can use diagnostic kits created in-house to test for infections of coronavirus-2019 (COVID-19). “We issued a policy this morning that allows us to have a lot of flexibility around the development of diagnostic tests,” said FDA Commissioner Stephen Hahn at a White House briefing with President Donald Trump this afternoon. “We expect this policy to have a significant impact.” The change could greatly expand the number of laboratories able to do coronavirus testing. The U.S. government has come under severe criticism for not providing nearly enough tests needed to understand the extent of spread in the population. A test kit produced and distributed by the U.S. Centers for Disease Control and Prevention (CDC) was shelved after state and local lab trying it out discovered that it contained a faulty reagent. As a result, many labs that have the capability to test themselves have not been allowed to do so. The new recommendations focus on “high-complexity testing laboratories” that are certified under federal rules known as Clinical Laboratory Improvement Amendments. This group of facilities includes many hospital labs, like the one that epidemiologist Michael Mina works at Brigham and Women’s Hospital in Boston. “Essentially it’s opening up a clear and concise avenue for labs like the one at Brigham and Women’s,” says Mina. “It’s what I’ve been advocating for a month now.”",2020,"Cohen, Jon",Science Magazine,1927230155,#2778,
,CZI,Psychological crisis interventions in Sichuan Province during the 2019 novel coronavirus outbreak,10.1016/j.psychres.2020.112895,,,,,2020,"Zhou, Xiaobo",Psychiatry Research,3006425298,#3033,
,CZI,The psychiatric impact of the novel coronavirus outbreak,10.1016/j.psychres.2020.112902,,,,,2020,"Carvalho, Poliana Moreira de Medeiros; Moreira, Marcial Moreno; de Oliveira, Matheus Nogueira Arcanjo; Landim, José Marcondes Macedo; Neto, Modesto Leite Rolim",Psychiatry Research,3004810054,#2749,
,CZI,Psychological crisis intervention during the outbreak period of new coronavirus pneumonia from experience in Shanghai,10.1016/j.psychres.2020.112903,,,,"Since the middle of December 2019, human-to-human transmission of novel coronavirus pneumonia (NCP) has occurred among close contacts. At the same time, greater attention should be paid to psychological crisis intervention (PCI) among affected populations, for the timely prevention of inestimable damage from a secondary psychological crisis. PCI has been initiated via remote (telephone and internet) and onsite medical services to help medical workers, patients, and others affected to overcome any psychological difficulties. This paper outlines experiences based on the work of the Shanghai Medical Team.",2020,"Jiang, Xixi; Deng, Lili; Zhu, Yuncheng; Ji, Haifeng; Tao, Lily; Liu, Li; Yang, Daoliang; Ji, Weidong",Psychiatry Research,2615103260,#2848,
,CZI,Wuhan novel coronavirus (COVID-19): why global control is challenging?,10.1016/j.puhe.2020.02.001,,,,,2020,"Lee, A.",Public Health,3006113744,#2609,
,CZI,And now for something completely different: from 2019-nCoV and COVID-19 to 2020-nMan,10.1016/j.pulmoe.2020.02.010,,,,"Infectious diseases have accompanied mankind since the beginning of humanity and have had a profound impact on the history and development of humanity and civilisation. This is natural if we are aware that microorganisms represent the majority of the biomass on planet Earth, and that there are more microorganisms, specifically bacteria, in the human body than there are cells. To be more precise, about 1012 human cells for every 1013 bacteria, as an adaptive advantage of the replication of bacteria that occurs every 20–40 min, as against tens of years in the human species. Infectious diseases, in particular pandemics and local epidemics, have influenced the course of wars, all descendants, including those of rulers, and the fate of peoples and nations.1 By way of example, we should remember the importance of malaria in the fall of the Roman Empire, the Black Death in the 14th century which killed nearly a third of the world’s population, and the impact of the “Spanish” flu pandemic of 1918–19 in Portugal, which in a few months decimated 1% of the Portuguese population and reduced average life expectancy to 20 years and, more recently, smallpox, declared eradicated by the World Health Organization (WHO) in 1980 as a result of vaccination,2 and with an estimated mortality in the 20th century of between 300 and 500 million people.3 In light of this impact, it is legitimate to consider infections one of the main modellers of mankind and of present and future generations, as well as generations of the descendants of survivors. We have also been major challengers of infectious diseases in the 21st century. Most notably in 2009 and 2010, when the 2009 influenza pandemic caused by the A (H1N1) subtype strain occurred, which originated in Mexico, with a virulence rate of 5–10% of the world’s population, and an estimated mortality of 300,000 people. In Portugal there were 124 deaths, with an average age of 47.6 years, corresponding to a crude death rate of 1.17 per 100,000 inhabitants.4 However, it is in the first decades of the 21st century when the number of outstanding cases corresponded entirely to Coronaviridae of the family Coronaviridae, from the Latin corona, given its crown shape under electronic microscope. These viruses belong to a large family of RNA viruses, with abundant expression in the animal kingdom, particularly bats, and also other mammals, birds and reptiles. The first outbreak of coronavirus disease was the result of a cross-species barrier jump, originating in bats, and probably the musk cat as a secondary host, which began on November 16, 2002 and was named SARS-CoV (Severe Acute Respiratory Syndrome - CoronaVirus) in Guangdong Province, of the People’s Republic of China, and extended to 17 countries, including Canada, the United States of America (USA), Australia, Germany, France, Sweden, the United Kingdom and Spain. The WHO declared an end to the risk of new cases on 19 May 2004, with an estimated total of approximately 8096 cases and at least 774 deaths.5",2020,"Froes, F.",Pulmonology,3006602665,#4676,
,CZI,High resolution CT features of novel coronavirus pneumonia in children,10.1016/j.radcr.2019.03.016,,,,"Objective To investigate the high resolution CT (HRCT) features of novel coronavirus pneumonia (NCP) in children . Methods A retrospective analysis was performed on the chest HRCT findings of 22 children diagnosed with 2019-nCov pneumonia by clinical and nucleic acid testing in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 25, 2020 to February 5, 2020. There were 12 boys and 10 girls, aged from 2 months to 14 years old, with a median age of 4 years, and 14 patients were under 5 years old. The characteristics of lung lesions on HRCT imaging such as distribution, shape, density, etc. and whether there were hilar and mediastinal lymph node enlargement and pleural changes were observed by 2 radiologists. Results In all of the 22 patients, 3 patients (3/22) had normal chest CT, and 19 patients (19/22) had infiltrated lesions in lung. Among them, 7 patients had unilateral lung involvement, 12 patients had bilateral involvement. The HRCT manifestations were as follows. Six patients showed ground glass shadow, including 4 cases showed light ground glass shadow and 2 had typical crazy paving sign. Four patients showed lung consolidation, with localized strip shadow and patchy high-density shadow. Six patients showed patchy lesions with surrounding ground glass shadow, including 1 case with white lung in the right. The bronchopneumonia-like changes in 3 cases, showed scattered spot-like or patchy uneven high-density shadows. The lesions in the lower lobe were more serious than those in the upper lobe, and the lesions in the lateroposterior zone of the lung were more common than those in the apical and central area of the lung. No enlarged lymph nodes and pleural effusion were seen in all patients, and 1 case had thickened interlobar pleura. Conclusions The HRCT manifestations of NCP in children are diversified, comprehensive judgments need to be made in combination with epidemiological data, clinical manifestations, and laboratory tests, but the chest HRCT can be used as an important basis for early clinical diagnosis and prevention and control interventions.",2020,"MA, Huijing; SHAO, Jianbo; WANG, Yongjiao; ZHAI, Aiguo; ZHENG, Nannan; LI, Quan; LIU, Yan",Chinese Journal of Radiology,2934726322,#2174,
,CZI,High resolution CT findings and clinical features of novel coronavirus pneumonia in Guangzhou,10.1016/j.radcr.2019.03.016,,,,"To investigate the initial HRCT manifestations and clinical features of imported novel coronavirus pneumonia (NCP) in Guangzhou. Methods. A retrospective analysis of 91 NCP patients admitted to the Guangzhou Eighth People&rsquo;s Hospital from January 22 to 30, 2020 was performed including 39 males and 52 females, with a median age of 50 (33-62) years, then their clinical features and HRCT characteristics were analyzed. Results. The main clinical presentations included fever in 70 cases and cough in 57 cases(mainly dry coughin39 cases). The first time HRCT showed that 24 cases with NCP were normal, however other 67 cases were abnormal. The ground glass opacity in the lung on HRCT was found in 65 cases, including 64 cases with dilated blood vessel crossing the lesion, 50 cases with thickened adjacent pleura, and 47 cases with thickening of interstitial septum. The patchy opacity was seen in 42 cases, and no enlarged lymph nodes were observed in all patients. As for the lesion distribution, there were two cases with bilateral diffuse changes, 57 cases with multiple lesions, 8 cases with the lesion in only one lobe. The lesions were mainly located under the pleura area in 46 cases, including 39 cases in the lower lobe and other 7 cases in the upper lobe. And there were 13 cases without characteristic distribution in the lung. Conclusions. The initial images of NCP in Guangzhou mainly showed multiple ground glass opacity, which were mostly seen in the subpleural and lower lung fields, most of them with thickened pulmonary interstitium. Guangzhou has a higher proportion of NCP patients with mild and general patients, and some confirmed patients show negative HRCT for the first time. Patients without HRCT changes should be reviewed in a timely manner.",2020,"Yu, Chengcheng; Qu, Jing; Zhang, Songfeng; Jiang, Songfeng; Chen, Bihua; Guan, Wanhua; Gan, Qingxin; Huang, Deyang; Ling, Zhoukun; Jiang, Rui; Lin, Lin; Liu, Jinxin",Chinese Journal of Radiology,2934726322,#1898,
,CZI,A Novel Coronavirus Emerges,10.1016/j.rce.2020.01.001,,32063263,,,2020,"Ena, J.; Wenzel, R. P.",Rev Clin Esp,3006338959,#1146,
,CZI,Key points of serious adverse eventand protection of patients in ophthalmic clinical trials during novel coronavirus pneumonia outbreak,10.1016/j.rmed.2019.02.021,,,,"The prevention and control of novel coronavirus pneumonia is the most priority recently, and various measures during the prevention and control period will have varying degrees of impact on the implement of clinical trials. However, various examinations in ophthalmological clinical trials need close contact between operators and patients, which put us at risk of cross-infection. This paper indicated some suggestions based on the criteria of clinical trials under major public health emergencies, the management of clinical trials during epidemic period including the follow-up of subjects, the treatment of epidemic serious adverse event (SAE) and the management requirements of co-sponsors, as well as the requirements and management principles for environment, subjects, examiners and inspection equipment in the process of ophthalmic clinical trials. It may be helpful to the ophthalmic clinical trial researchers and subjects during the period of novel coronavirus infection.",2020,"ZHANG, Peng; LU, Yingyi; SONG, Shuang; YU, Xiaobing; DAI, Hong",Chinese Journal of Experimental Ophthalmology,2921734897,#2062,
,CZI,Community pharmacist in public health emergencies: Quick to action against the coronavirus 2019-nCoV outbreak,10.1016/j.sapharm.2020.02.003,,,,"The 2019-nCoV infection that is caused by a novel strain of coronavirus was first detected in China in the end of December 2019 and declared a public health emergency of international concern by the World Health Organization on January 30, 2020. Community pharmacists in one of the first areas that had confirmed cases of the viral infection, Macau, joined the collaborative force in supporting the local health emergency preparedness and response arrangements. This paper aimed to improve the understanding of community pharmacists’ role in case of 2019-CoV outbreak based on the practical experiences in consultation with the recommendations made by the International Pharmaceutical Federation on the Coronavirus 2019-nCoV outbreak.",2020,"Lam Ung, Carolina Oi",Research in Social and Administrative Pharmacy,3005668029,#762,
,CZI,A data driven time-dependent transmission rate for tracking an epidemic: a case study of 2019-nCoV,10.1016/j.scib.2020.02.005,,,,,2020,"Huang, Norden E.; Qiao, Fangli",Science Bulletin,3005064183,#492,
,CZI,The inflection point about COVID-19 may have passed,10.1016/j.scib.2020.02.025,,,,,2020,"Gu, Chaolin; Zhu, Jie; Sun, Yifei; Zhou, Kai; Gu, Jiang",Science Bulletin,1969146377,#3170,
,CZI,A disconnected policy network: The UK's response to the Sierra Leone Ebola epidemic,10.1016/j.socscimed.2020.112851,,,,"This paper investigates whether the inclusion of social scientists in the UK policy network that responded to the Ebola crisis in Sierra Leone (2013–16) was a transformational moment in the use of interdisciplinary research. In contrast to the existing literature, that relies heavily on qualitative accounts of the epidemic and ethnography, this study tests the dynamics of the connections between critical actors with quantitative network analysis. This novel approach explores how individuals are embedded in social relationships and how this may affect the production and use of evidence. The meso-level analysis, conducted between March and June 2019, is based on the traces of individuals' engagement found in secondary sources. Source material includes policy and strategy documents, committee papers, meeting minutes and personal correspondence. Social network analysis software, UCINet, was used to analyse the data and Netdraw for the visualisation of the network. Far from being one cohesive community of experts and government officials, the network of 134 people was weakly held together by a handful of super-connectors. Social scientists’ poor connections to the government embedded biomedical community may explain why they were most successful when they framed their expertise in terms of widely accepted concepts. The whole network was geographically and racially almost entirely isolated from those affected by or directly responding to the crisis in West Africa. Nonetheless, the case was made for interdisciplinarity and the value of social science in emergency preparedness and response. The challenge now is moving from the rhetoric to action on complex infectious disease outbreaks in ways that value all perspectives equally.",2020,"Georgalakis, James",Social Science & Medicine,3006112521,#817,
,CZI,EuNPs-mAb fluorescent probe based immunochromatographic strip for rapid and sensitive detection of porcine epidemic diarrhea virus,10.1016/j.talanta.2020.120865,,,,"Porcine epidemic diarrhea (PED), induced by porcine epidemic diarrhea virus (PEDV) causes acute diarrhea, vomiting, dehydration and high mortality in neonatal piglets, resulting in significant economic losses in the pig industries. In this study, an immunochromatographic assay (ICA) based on a EuNPs-mAb fluorescent probe was developed and optimized for rapid detection of PEDV. The limit of detection (LOD) of the ICA was 0.218 μg/mL (2.725 × 103 TCID50/mL) and its linear detection range was 0.03125–8 μg/mL (3.91 × 102-105 TCID50/mL). The ICA was also validated for the detection of PEDV in swine stool samples. 60 swine stool samples from southern China were analyzed by the ICA and RT-PCR, and the results showed that the coincidence rate of the ICA to RT-PCR was 86.67%, which was significantly higher than that of AuNPs based ICA. The ICA is sensitive and specific and can achieve on-site rapid detection of swine stool samples. Therefore, the ICA has a great potential for PED diagnosis and prevention.",2020,"Xu, Fei; Jin, Zhiyuan; Zou, Siyi; Chen, Chaoqun; Song, Qifang; Deng, Shengchao; Xiao, Wei; Zhang, Xiaoli; Jia, Aiqing; Tang, Yong",Talanta,2084580389,#2107,
,CZI,Unveiling the Origin and Transmission of 2019-nCoV,10.1016/j.tim.2020.02.001,,,,"A novel coronavirus has caused thousands of human infections in China since December 2019, raising a global public health concern. Recent studies (Huang et al., Chan et al., and Zhou et al.) have provided timely insights into its origin and ability to spread among humans, informing infection prevention and control practices.",,"Xu, Yifei",Trends in Microbiology,2747380789,#1734,
,CZI,"SARS-CoV, MERS-CoV and now the 2019-novel CoV: Have we investigated enough about coronaviruses? – A bibliometric analysis",10.1016/j.tmaid.2020.101566,,,,,2020,"Bonilla-Aldana, D. Katterine; Quintero-Rada, Keidenis; Montoya-Posada, Juan Pablo; Ramírez, Sebastian; Paniz-Mondolfi, Alberto; Rabaan, Ali; Sah, Ranjit; Rodríguez-Morales, Alfonso J.",Travel Medicine and Infectious Disease,,#64,
,CZI,"The next big threat to global health? 2019 novel coronavirus (2019-nCoV): What advice can we give to travellers? – Interim recommendations January 2020, from the Latin-American society for Travel Medicine (SLAMVI)",10.1016/j.tmaid.2020.101567,,,,,2020,"Biscayart, Cristian; Angeleri, Patricia; Lloveras, Susana; Chaves, Tânia do Socorro Souza; Schlagenhauf, Patricia; Rodríguez-Morales, Alfonso J.",Travel Medicine and Infectious Disease,,#67,
,CZI,The association between domestic train transportation and novel coronavirus (2019-nCoV) outbreak in China from 2019 to 2020: A data-driven correlational report,10.1016/j.tmaid.2020.101568,,32006656,,,2020,"Zhao, Shi; Zhuang, Zian; Ran, Jinjun; Lin, Jiaer; Yang, Guangpu; Yang, Lin; He, Daihai",Travel medicine and infectious disease,3003807992,#4317,
,CZI,Outbreak of novel Corona Virus (2019-nCoV); implications for travelers to Pakistan?,10.1016/j.tmaid.2020.101571,,,,,2020,"Rahman Qureshi, Ubaid Ur; Saleem, Sadia; Khan, Aisha; Afzal, Muhammad Sohail; Ali, Muhammad Shahzad; Ahmed, Haroon",Travel Medicine and Infectious Disease,3005325774,#218,
,CZI,"What goes on board aircraft? Passengers include Aedes, Anopheles, 2019-nCoV, dengue, Salmonella, Zika, et al",10.1016/j.tmaid.2020.101572,,,,,2020,"Wilson, Mary E.",Travel Medicine and Infectious Disease,3004776013,#365,
,CZI,"Maps, masks and media – Traveller and practitioner resources for 2019 novel coronavirus (2019-nCoV) acute respiratory virus",10.1016/j.tmaid.2020.101574,,,,,2020,"Chiodini, Jane",Travel Medicine and Infectious Disease,,#490,
,CZI,"Coronavirus infections reported by ProMED, February 2000–January 2020",10.1016/j.tmaid.2020.101575,,,,"Introduction Sources describing the global burden of emerging diseases accurately are still limited. We reviewed coronavirus infections reported by ProMED and assessed the reliability of the data retrieved compared to published reports. We evaluated the effectiveness of ProMED as a source of epidemiological data on coronavirus. Methods Using the keyword “coronavirus” in the ProMED search engine, we reviewed all the information from the reports and collected data using a structured form, including year, country, gender, occupation, the number of infected individuals, and the number of fatal cases. Results We identified 109 entries reported between February 29, 2000 and January 22, 2020. A total of 966 cases were reported, with death reported in 188 cases, suggesting an overall case fatality rate (CFR) of 19.5%. Of 70 cases for which the gender was reported, 47 (67.1%) were male. Most of the cases were reported from China, the United Arab Emirates, and Saudi Arabia, with reports from other countries, including imported cases in Europe and North America. Conclusions Internet-based reporting systems such as ProMED are useful to gather information and synthesize knowledge on emerging infections. Although certain areas need to be improved, ProMED provided useful information about coronaviruses especially during outbreaks.",2020,"Bonilla-Aldana, D. Katterine; Holguin-Rivera, Yeimer; Cortes-Bonilla, Isabella; Cardona-Trujillo, María C.; García-Barco, Alejandra; Bedoya-Arias, Hugo A.; Rabaan, Ali A.; Sah, Ranjit; Rodriguez-Morales, Alfonso J.",Travel Medicine and Infectious Disease,,#424,
,CZI,Coronavirus 2019-nCoV: Is the genie already out of the bottle?,10.1016/j.tmaid.2020.101577,,,,,2020,"Hanscheid, Thomas; Valadas, Emília; Grobusch, Martin P.",Travel Medicine and Infectious Disease,3004801973,#489,
,CZI,Going global – Travel and the 2019 novel coronavirus,10.1016/j.tmaid.2020.101578,,,,,2020,"Rodríguez-Morales, Alfonso J.; MacGregor, Kirsten; Kanagarajah, Sanch; Patel, Dipti; Schlagenhauf, Patricia",Travel Medicine and Infectious Disease,,#487,
,CZI,The COVID-19 outbreak and implications for the Tokyo 2020 Summer Olympic Games,10.1016/j.tmaid.2020.101604,,,,,2020,"Gallego, Viviana; Nishiura, Hiroshi; Sah, Ranjit; Rodriguez-Morales, Alfonso J.",Travel Medicine and Infectious Disease,2891291435,#2288,
,CZI,"Clinical characteristics of laboratory confirmed positive cases of SARS-CoV-2 infection in Wuhan, China: A retrospective single center analysis",10.1016/j.tmaid.2020.101606,,,,,2020,"Huang, Yihui; Tu, Mengqi; Wang, Shipei; Chen, Sichao; Zhou, Wei; Chen, Danyang; Zhou, Lin; Wang, Min; Zhao, Yan; Zeng, Wen; Huang, Qi; Xu, Hai'bo; Liu, Zeming; Guo, Liang",Travel Medicine and Infectious Disease,2897243354,#2839,
,CZI,COVID-19: Zoonotic aspects,10.1016/j.tmaid.2020.101607,,,,,2020,"Ahmad, Tauseef; Khan, Muhammad; Haroon; Musa, Taha Hussein; Nasir, Saima; Hui, Jin; Bonilla-Aldana, D. Katterine; Rodriguez-Morales, Alfonso J.",Travel Medicine and Infectious Disease,2921548154,#2451,
,CZI,Asymptomatic coronavirus infection: MERS-CoV and SARS-CoV-2 (COVID-19),10.1016/j.tmaid.2020.101608,,,,,2020,"Al-Tawfiq, Jaffar A.",Travel Medicine and Infectious Disease,2921429935,#2444,
,CZI,COVID-19 in Latin America: The implications of the first confirmed case in Brazil,10.1016/j.tmaid.2020.101613,,32126292,,,2020,"Rodriguez-Morales, Alfonso J.; Gallego, Viviana; Escalera-Antezana, Juan Pablo; Mendez, Claudio A.; Zambrano, Lysien I.; Franco-Paredes, Carlos; Suárez, Jose A.; Rodriguez-Enciso, Hernan D.; Balbin-Ramon, Graciela Josefina; Savio-Larriera, Eduardo; Risquez, Alejandro; Cimerman, Sergio",Travel Med Infect Dis,2026978646,#3315,
,CZI,Remdesivir as a possible therapeutic option for the COVID-19,10.1016/j.tmaid.2020.101615,,,,,2020,"Al-Tawfiq, Jaffar A.; Al-Homoud, Ali H.; Memish, Ziad A.",Travel Medicine and Infectious Disease,2985999596,#4636,
,CZI,Positive result of Sars-Cov-2 in sputum from a cured patient with COVID-19,10.1016/J.TMAID.2020.101619,,,,"ince December 2019, an outbreak of the novel coronavirus (SARS-CoV-2) infection has spread rapidly in Wuhan, China [1]1. Over a month since the outbreak, more than 13,000 patients with COVID-19 have be cured and discharged from hospital until now. For the clinical cure criteria in China, twice successive negative results of Sars-Cov-2 nucleic acid detection are the important index, in addition to normal body temperature for 3 days as well as obvious improvement in respiratory symptoms and CT scan [2]. In the present work, we reported that Sars-Cov-2 nucleic acid was still detectable in sputum obtained by nebulization from a cured patient. On January 22, a 49-year-old man presented himself with fever for 4 days to a clinic. Throat swab detection was positive for SARS-CoV-2 nucleic acid by real-time RT-PCR. Subsequently, the patient was diagnosed with COVID-19 according to the diagnostic criteria [2] as follows (1): the positive result of SARS-CoV-2 nucleic acid detection (2); a history of short stay in Wuhan within 14 days; and (3) symptoms of fever, and multiple patchy areas of ground-glass opacity on CT scan. After the active treatment, the patient recovered from fever and other respiratory symptoms on February 4. On February 9 and February 10, the SARS-CoV-2 nucleic acid detection was successively negative in his throat swab samples. The CT scan result showed that the inflammation was significantly decreased in both lungs. Both the results of SARS-CoV-2 nucleic acid detection and CT scans indicated a recovery trend, and the patient was ready for discharge. On February 13, the throat swab and sputum by nebulization were collected before the patient was discharged. Notably, SARS-CoV-2 nucleic acid was still detected in sputum from the patient although negative result of throat swab detection.",2020,"Qu, Ye-Min; Cong, Hai-Yan",Travel Medicine and Infectious Disease,3006645647,#4977,
,CZI,Coronavirus Disease 2019: Coronaviruses and Blood Safety,10.1016/j.tmrv.2020.02.003,,,,"With the outbreak of unknown pneumonia in Wuhan, China in December 2019, a new coronavirus, Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) aroused the attention of the entire world. The current outbreak of infections with SARS-CoV-2 is termed Corona Virus Disease- 2019 (COVID-19). The World Health Organization (WHO) declared COVID-19 in China as a Public Health Emergency of International Concern (PHEIC). Two other corona virus infections-- SARS in 2002–2003 and Middle East Respiratory Syndrome (MERS) in 2012-- both caused severe respiratory syndrome in humans. All three of these emerging infectious diseases leading to a global spread are caused by beta-coronaviruses. Although coronaviruses usually infect the upper or lower respiratory tract, viral shedding in plasma or serum is common. Therefore, there is still a theoretical risk of transmission of coronaviruses through the transfusion of labile blood products. Because more and more asymptomatic infections are being found among COVID-19 cases, considerations of blood safety and coronaviruses have arisen especially in endemic areas. In this review, we detail current evidence and understanding of the transmission of SARS-CoV, MERS-CoV and SARS-CoV-2 through blood products as of February 10, 2020 and also discuss pathogen inactivation methods on coronaviruses.",2020,"Chang, Le; Yan, Ying; Wang, Lunan",Transfusion Medicine Reviews,2892593968,#1681,
,CZI,COVID-19 and blood safety: help with a dilemma,10.1016/j.tmrv.2020.02.004,,,,,2020,"Dodd, Roger Y.; Stramer, Susan L.",Transfusion Medicine Reviews,2785996973,#1998,
,CZI,"Another coronavirus, another epidemic, another warning",10.1016/j.vaccine.2020.02.039,,,,,2020,"Poland, Gregory A.",Vaccine,2302832176,#1361,
,CZI,Efficacy of orally administered porcine epidemic diarrhea vaccine-loaded hydroxypropyl methylcellulose phthalate microspheres and RANKL-secreting L. lactis,10.1016/j.vetmic.2020.108604,,,,"Here, we examined the efficacy of are combinant subunit antigen-based oral vaccine for preventing porcine epidemic diarrhea virus (PEDV). First, we generated a soluble recombinant partial spike S1 protein (aP2) from PEDV in E. coli and then evaluated the utility of aP2 subunit vaccine-loaded hydroxypropyl methylcellulose phthalate microspheres (HPMCP) and RANKL-secreting L. lactis (LLRANKL) as a candidate oral vaccine in pregnant sows. Pregnant sows were vaccinated twice (with a 2 week interval between doses) at 4 weeks before farrowing. Titers of virus-specific IgA antibodies in colostrum, and neutralizing antibodies in serum, of sows vaccinated with HPMCP (aP2) plus LL RANKL increased significantly at 4 weeks post-first vaccination. Furthermore, the survival rate of newborn suckling piglets delivered by sows vaccinated with HPMCP (aP2) plus LL RANKL was similar to that of piglets delivered by sows vaccinated with a commercial killed porcine epidemic diarrhea virus (PED) vaccine. The South Korean government promotes a PED vaccine program (live-killed-killed) to increase the titers of IgA and IgG antibodies in pregnant sows and prevent PEDV. The oral vaccine strategy described herein, which is based on a safe and efficient recombinant subunit antigen, is an alternative PED vaccination strategy that could replace the traditional strategy, which relies on attenuated live oral vaccines or artificial infection with virulent PEDV.",2020,"Choe, SeEun; Song, Sok; Piao, Dachuan; Park, Gyu-Nam; Shin, Jihye; Choi, Yun-Jaie; Kang, Sang-Kee; Cha, Ra Mi; Hyun, Bang-Hun; Park, Bong-Kyun; An, Dong-Jun",Veterinary Microbiology,3005277414,#2324,
,CZI,Swine acute diarrhea syndrome coronavirus (SADS-CoV) antagonizes interferon-β production via blocking IPS-1 and RIG-I,10.1016/j.virusres.2019.197843,,,,"Swine acute diarrhea syndrome coronavirus (SADS-CoV), a newly emerging enteric coronavirus, is considered to be associated with swine acute diarrhea syndrome (SADS) which has caused significantly economic losses to the porcine industry. Interactions between SADS-CoV and the host innate immune response is unclear yet. In this study, we used IPEC-J2 cells as a model to explore potential evasion strategies employed by SADS-CoV. Our results showed that SADS-CoV infection failed to induce IFN-β production, and inhibited poly (I:C) and Sendai virus (SeV)-triggered IFN-β expression. SADS-CoV also blocked poly (I:C)-induced phosphorylation and nuclear translocation of IRF-3 and NF-κB. Furthermore, SADS-CoV did not interfere with the activity of IFN-β promoter stimulated by IRF3, TBK1 and IKKε, but counteracted its activation induced by IPS-1 and RIG-I. Collectively, this study is the first investigation that shows interactions between SADS-CoV and the host innate immunity, which provides information of the molecular mechanisms underlying SASD-CoV infection.",2020,"Zhou, Zhihai; Sun, Yuan; Yan, Xiaoling; Tang, Xiaoyu; Li, Qianniu; Tan, Yaorong; Lan, Tian; Ma, Jingyun",Virus Research,,#2043,
,CZI,"Genetic characterization and phylogenetic analysis of porcine deltacoronavirus (PDCoV) in Shandong Province, China",10.1016/j.virusres.2020.197869,,,,"Porcine deltacoronavirus (PDCoV) is the etiological agent of acute diarrhoea and vomiting in pigs, threatening the swine industry worldwide. Although several PDCoV studies have been conducted in China, more sequence information is needed to understand the molecular characterization of PDCoV. In this study, the partial ORF1a, spike protein (S) and nucleocapsid protein (N) were sequenced from Shandong Province between 2017 and 2018. The sequencing results for the S protein from 10 PDCoV strains showed 96.7 %–99.7 % nucleotide sequence identity with the China lineage strains, while sharing a lower level of nucleotide sequence identity, ranging from 95.7 to 96.8%, with the Vietnam/Laos/Thailand lineage strains. N protein sequencing analysis showed that these strains showed nucleotide homologies of 97.3%–99.3% with the reference strains. Phylogenetic analyses based on S protein sequences showed that these PDCoV strains were classified into the China lineage. The discontinuous 2 + 3 aa deletions at 400–401 and 758–760 were found in the Nsp2 and Nsp3 coding region in five strains, respectively, with similar deletions having been identified in Vietnam, Thailand, and Laos. Three novel patterns of deletion were observed for the first time in the Nsp2 and Nsp3 regions. Importantly, those findings suggest that PDCoV may have undergone a high degree of variation since PDCoV was first detected in China.",2020,"Sun, Wenchao; Wang, Li; Huang, Haixin; Wang, Wei; Cao, Liang; Zhang, Jinyong; Zheng, Min; Lu, Huijun",Virus Research,3000185706,#2388,
,CZI,The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines,10.1016/S0140-6736(03)13412-5,,,,"The outbreak of 2019-novel coronavirus disease (COVID-19) that is caused by SARS-CoV-2 has spread rapidly in China, and has developed to be a Public Health Emergency of International Concern. However, no specific antiviral treatments or vaccines are available yet. This work aims to share strategies and candidate antigens to develop safe and effective vaccines against SARS-CoV-2. An outbreak of 2019-novel coronavirus (SARS-CoV-2) that causes atypical pneumonia (COVID-19) has raged in China since mid-December 2019 and has spread to 26 countries (February 20, 2020). The epidemic was identified by the first four cases confirmed on December 29, 2019 and was traced to the Huanan Seafood Wholesale Market, Wuhan city, Hubei Province, China1. A total of 75,465 cases with SARS-CoV-2 infections have been confirmed up to date (February 20, 2020), and 2,236 people have died in China2. COVID-19 spreads rapidly by human-to-human transmission with a median incubation period of 3.0 days (range, 0 to 24.0), and the time from symptom onset to developing pneumonia is 4.0 days (range, 2.0 to 7.0)3. Respiratory droplets and direct contact are conventional transmission routes for SARS-CoV-2, and fecal-to-oral transmission might also have a role3. Fever, dry cough, and fatigue are common symptoms at onset of COVID-194. Most patients have lymphopenia and bilateral ground-glass opacity changes on chest CT scans4,5. No specific antiviral treatments or vaccines are available because it is a new emerging viral disease. Development of SARS-CoV-2-based vaccines is urgently required. The entire virus particle-based preparation of vaccines, including inactivated and attenuated virus vaccines is advisable, because it is based on previous studies about the prevention and control of seasonal influenza vaccines6. The first SARS-CoV-2 (Wuhan-Hu-1) was successfully sequenced and its genomic sequence submitted to GenBank on January 5, 2020 (Accession no. MN908947.3)7. Subsequently large-scale culture of SARS-CoV-2 was quickly performed, and an inactivated virus vaccine could be prepared through the employment of established physical and chemical methods such as UV light, formaldehyde, and β-propiolactone8. The development of attenuated-virus vaccines is also possible by carefully screening the serially propagated SARS-CoV-2 with reduced pathogenesis such as induced minimal lung injury, diminished limited neutrophil influx, and increased anti-inflammatory cytokine expressions compared with the wild-type virus9. Both inactivated and attenuated virus vaccines have their own disadvantages and side effects (Table 1). Alternatively, new vaccine designs based on the putative protective antigen/peptides derived from SARS-CoV-2 should be considered",2020,"Shang, Weilong; Yang, Yi; Rao, Yifan; Rao, Xiancai",,2129542667,#5211,
,CZI,Viral Load Kinetics of SARS-CoV-2 Infection in First Two Patients in Korea,10.1016/S0140-6736(07)60497-8,,32080991,,"As of February 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak started in China in December 2019 has been spreading in many countries in the world.With the numbers of confirmed cases are increasing, information on the epidemiologic investigation and clinical manifestation have been accumulated. However, data on viral load kinetics in confirmed cases are lacking. Here, we present the viral load kinetics of the first two confirmed patients with mild to moderate illnesses in Korea in whom distinct viral load kinetics are shown. This report suggests that viral load kinetics of SARS-CoV-2 may be different from that of previously reported other coronavirus infections such as SARS-CoV.",2020,"Kim, Jin Yong",Journal of Korean Medical Science,2139772076,#3706,
,CZI,Middle East respiratory syndrome,10.1016/S0140-6736(19)33221-0,,,,"The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012. Intermittent sporadic cases, community clusters, and nosocomial outbreaks of MERS-CoV continue to occur. Between April 2012 and December 2019, 2499 laboratory-confirmed cases of MERS-CoV infection, including 858 deaths (34·3% mortality) were reported from 27 countries to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths). Large outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by WHO as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. This Seminar provides an update on the current knowledge and perspectives on MERS epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, development of new therapeutics and vaccines, and highlights unanswered questions and priorities for research, improved management, and prevention.",,"Memish, Ziad A.; Perlman, Stanley; Van Kerkhove, Maria D.; Zumla, Alimuddin",The Lancet,2112147913,#3836,
,CZI,Responding to health emergencies in the Eastern Mediterranean region in times of conflict,10.1016/S0140-6736(20)30069-6,,,,"WHO's Eastern Mediterranean region (EMR) is facing emergencies on a scale that is perhaps unprecedented in its history. There is armed conflict in 12 of the region's 22 countries.1 , 2 The region's 680 million people3 represent 9% of the global population, yet the EMR is home to 43% of those who need humanitarian assistance4 and is the source of 64% of the world's refugees.5 The health effects of these crises are immense. Direct health consequences include trauma-related deaths and disability, gender-based violence, and mental disorders. Disruption of health systems contributes to increased morbidity and mortality from infectious diseases, malnutrition, obstetric complications, and non-communicable diseases (NCDs). Health indicators in the EMR are among the worst in the world.6 State fragility and conflict are among the biggest challenges to attainment of Sustainable Development Goal 3.7 Conflict is a global health security threat because affected countries are less able to prevent, detect, and respond to disease outbreaks. More than 70% of disease outbreaks worldwide occur in fragile and conflict-affected settings.8 Yemen has experienced the largest cholera outbreak in history.9 During the second half of 2019, there were six concurrent disease outbreaks in Sudan.10 Wild polio virus returned to Syria due to conflict,11 while Afghanistan and Pakistan are two of three countries where the virus remains endemic.12 The average International Health Regulations (IHR) core capacity score is much lower for the 12 conflict-affected countries than for the other countries in the region,6 placing them at greater risk of spread and public health consequences of the ongoing outbreak of coronavirus disease 2019 (COVID-19) and other epidemic-prone diseases. WHO's global COVID-19 strategic preparedness and response plan13 therefore prioritises countries with weak health systems for technical and operational support from international partners. COVID-19 has already affected ten countries in the region, as of Feb 28, 2020, including Afghanistan, Iraq, and Pakistan.",,"Brennan, Richard; Hajjeh, Rana; Al-Mandhari, Ahmed",The Lancet,2508300253,#3209,
,CZI,A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster,10.1016/S0140-6736(20)30154-9,,,,"BackgroundAn ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date.",,"Chan, Jasper Fuk-Woo; Yuan, Shuofeng; Kok, Kin-Hang; To, Kelvin Kai-Wang; Chu, Hin; Yang, Jin; Xing, Fanfan; Liu, Jieling; Yip, Cyril Chik-Yan; Poon, Rosana Wing-Shan; Tsoi, Hoi-Wah; Lo, Simon Kam-Fai; Chan, Kwok-Hung; Poon, Vincent Kwok-Man; Chan, Wan-Mui; Ip, Jonathan Daniel; Cai, Jian-Piao; Cheng, Vincent Chi-Chung; Chen, Honglin; Hui, Christopher Kim-Ming; Yuen, Kwok-Yung",The Lancet,3002539152,#20,
,CZI,"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China",10.1016/S0140-6736(20)30183-5,,31986264,,"A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients.|All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not.|By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα.|The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies.|Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.",2020,"Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; Cheng, Z.; Yu, T.; Xia, J.; Wei, Y.; Wu, W.; Xie, X.; Yin, W.; Li, H.; Liu, M.; Xiao, Y.; Gao, H.; Guo, L.; Xie, J.; Wang, G.; Jiang, R.; Gao, Z.; Jin, Q.; Wang, J.; Cao, B.",Lancet,3001118548,#34,
,CZI,Analysis of clinical features of 153 patients with novel coronavirus pneumonia in Chongqing,10.1016/S0140-6736(20)30183-5,,,,"Objective To analyze the clinical data of 153 patients with novel coronavirus pneumonia (COVID-19) in chongqing ,and provide reference and thinking for the diagnosis and treatment. Methods Analyze the clinical data, laboratory examination and chest imaging characteristics of 153 COVID-19 patients in Chongqing Public Health Medical Center from January 26 to February 5, 2020. According to the relevant diagnostic criteria ,patients were divided into non-severe group(n=132) and severe group(n=21),and analyze the correlation between serum index changes and disease severity. Results Combined with diabetes and chronic respiratory diseases, the severity of the disease was statistically significant ( &chi; 2 =11.04&#21644;6.94, P &lt;0.05). No symptoms were found in patients with mild illness ( &chi; 2 =4.09, P &lt;0.05) .The proportion of fever and muscle soreness in the severe group was higher than that in the non-severe group ( &chi; 2 =4.40 and 22.67, P &lt;0.05).Among the concomitant symptoms, the proportion of cough and shortness of breath in the severe group was higher than that in the non-severe group ( &chi; 2 =8.46 and 4.80, P &lt;0.05).C-reactive protein and d-dimer were higher in the severe group than in the non-severe group ( t =43.44 and 37.13, P &lt;0.05), and the number of CD 3 + T lymphocyte cells, CD 4 + T lymphocyte cells and CD 8 + T lymphocyte cells in the severe group was lower than that in the non-severe group (Z=27.25, 20.60 and 17.36, P &lt;0.05).Compared with the non-severe group, both lungs and the right lung lower lobe were more susceptible to involved ( &chi; 2 =6.95&#21644;20.39, P &lt;0.05) . Conclusion Severity of COVID-19 was associated with underlying disease, symptoms, site of involvement, C-reactive protein, d-dimer, CD 3 + T lymphocyte count, CD 4 + T lymphocyte count, and CD 8 + T lymphocyte count.&nbsp;",2020,"WAN, Qiu",Chinese Journal of Clinical Infectious Diseases,3001118548,#2137,
,CZI,Clinical features of 2019 novel coronavirus infection patients and a feasible screening procedure,10.1016/S0140-6736(20)30183-5,,,,"Objective To study the clinical characteristics of 2019 coronavirus (2019-nCoV) pneumonia patients and make a feasible screening process in fever clinic. Methods Epidemiologic features, clinical presentation, laboratory findings and image features of the screened patients were retrospectively collected and analyzed. Results Totally, 46 patients were screened, 9 of them were laboratory-confirmed 2019-nCoV infection, and others were defined as laboratory-excluded patients. Laboratory-confirmed patients had higher frequency of travelling or residence in Wuhan within two weeks of onset (P&lt;0.05), but there were no differences on age, sex, other epidemiologic features and comorbidities between the two groups (P&gt;0.05). The most common feature of the laboratory-confirmed patients was fever (100%), but the symptoms showed no differences between the two groups (P&gt;0.05). Laboratory-confirmed patients had lower white blood cell count than the laboratory-excluded patients (P&lt;0.05), and all of them had pneumonia in chest CT scan. None of the patients with normal chest CT had positive 2019-nCoV nucleic acid test. Conclusions No specific symptom was helpful in the diagnosis of 2019-nCoV infection. However, patients without chest CT scan changes had a very low risk of 2019-nCoV infection despite of the epidemiologic history and fever. We recommended a screening procedure that might be helpful to reduce the rate of miss diagnosis and improve screening efficiency.",2020,"LI, Yan; XU, Shengyong; DU, Tiekuan; XU, Jun; LI, Yi; YU, Xuezhong; ZHU, Huadong",Chinese Journal of Emergency Medicine,3001118548,#2201,
,CZI,Data sharing and outbreaks: best practice exemplified,10.1016/S0140-6736(20)30184-7,,,,,2020,"Heymann, David L.",The Lancet,3001293154,#844,
,CZI,Emerging understandings of 2019-nCoV,10.1016/S0140-6736(20)30186-0,,31986259,,,2020,The Lancet,Lancet,3004668429,#25,
,CZI,"Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study",10.1016/S0140-6736(20)30211-7,,,,"BackgroundIn December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia.",,"Chen, Nanshan; Zhou, Min; Dong, Xuan; Qu, Jieming; Gong, Fengyun; Han, Yang; Qiu, Yang; Wang, Jingli; Liu, Ying; Wei, Yuan; Xia, Jia'an; Yu, Ting; Zhang, Xinxin; Zhang, Li",The Lancet,3002108456,#78,
,CZI,Clinical research progresss of antiviral drugs for the novel coronavirus pneumonia,10.1016/S0140-6736(20)30211-7,,,,"The novel coronavirus (2019-nCoV or SARS-CoV-2) is a highly contagious and deadly virus that has infected more than 50 000 people and killed more than 1 000 people in 25 countries around the world. People who infected by the novel coronavirus may suffer from fever and cough, some may gradually appear breathing difficulties and other serious manifestations, some severe patients may have acute respiratory distress syndrome and septic shock leading to death. However, there are no definite and effective antiviral drugs for the novel coronavirus pneumonia all around the world. Therefore, this article aims to provide new idea for the effective treatment of the novel coronavirus pneumonia by summarizing the basic research and clinical progress of antiviral drugs at home and abroad.",2020,"WU, Weigang; YANG, Guilin; ZENG, Xiaobin; WU, Shipin; ZHOU, Boping",Chinese Journal of Experimental and Clinical Virology,3002108456,#2120,
,CZI,Offline: 2019-nCoV outbreak&#x2014;early lessons,10.1016/S0140-6736(20)30212-9,,,,,2020,"Horton, Richard",The Lancet,3004037946,#77,
,CZI,A novel coronavirus outbreak of global health concern - Comment - Correction,10.1016/S0140-6736(20)30250-6,,,,"Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet 2020; published online Jan 24. https://dox.doi.org/S0140-6736(20)30185-9—In this. Comment, the first sentence of the third paragraph should have read “Of the 41 patients in this cohort, 22 (55%) developed severe dyspnoea and 13 (32%) required admission to an intensive care unit, and six died.” And in the table, the title of the third row should have read “Location of first detection”. These corrections have been made to the online version as of Jan 29, 2020, and will be made to the printed version.",2020,"Chen Wang, Peter W Horby, Frederick G Hayden, George F Gao",The Lancet,3001465255,#847,
,CZI,Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding,10.1016/S0140-6736(20)30251-8,,,,"BackgroundIn late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed.",,"Lu, Roujian; Zhao, Xiang; Li, Juan; Niu, Peihua; Yang, Bo; Wu, Honglong; Wang, Wenling; Song, Hao; Huang, Baoying; Zhu, Na; Bi, Yuhai; Ma, Xuejun; Zhan, Faxian; Wang, Liang; Hu, Tao; Zhou, Hong; Hu, Zhenhong; Zhou, Weimin; Zhao, Li; Chen, Jing; Meng, Yao; Wang, Ji; Lin, Yang; Yuan, Jianying; Xie, Zhihao; Ma, Jinmin; Liu, William J.; Wang, Dayan; Xu, Wenbo; Holmes, Edward C.; Gao, George F.; Wu, Guizhen; Chen, Weijun; Shi, Weifeng; Tan, Wenjie",The Lancet,3004318991,#80,
,CZI,"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China (vol 395, pg 497, 2020)",10.1016/s0140-6736(20)30252-x,,,,,2020,"Huang, C.; Wang, Y.; Li, X.",Lancet,3001118548,#3649,
,CZI,"Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study",10.1016/S0140-6736(20)30260-9,,,,"Summary Background Since Dec 31, 2019, the Chinese city of Wuhan has reported an outbreak of atypical pneumonia caused by the 2019 novel coronavirus (2019-nCoV). Cases have been exported to other Chinese cities, as well as internationally, threatening to trigger a global outbreak. Here, we provide an estimate of the size of the epidemic in Wuhan on the basis of the number of cases exported from Wuhan to cities outside mainland China and forecast the extent of the domestic and global public health risks of epidemics, accounting for social and non-pharmaceutical prevention interventions. Methods We used data from Dec 31, 2019, to Jan 28, 2020, on the number of cases exported from Wuhan internationally (known days of symptom onset from Dec 25, 2019, to Jan 19, 2020) to infer the number of infections in Wuhan from Dec 1, 2019, to Jan 25, 2020. Cases exported domestically were then estimated. We forecasted the national and global spread of 2019-nCoV, accounting for the effect of the metropolitan-wide quarantine of Wuhan and surrounding cities, which began Jan 23–24, 2020. We used data on monthly flight bookings from the Official Aviation Guide and data on human mobility across more than 300 prefecture-level cities in mainland China from the Tencent database. Data on confirmed cases were obtained from the reports published by the Chinese Center for Disease Control and Prevention. Serial interval estimates were based on previous studies of severe acute respiratory syndrome coronavirus (SARS-CoV). A susceptible-exposed-infectious-recovered metapopulation model was used to simulate the epidemics across all major cities in China. The basic reproductive number was estimated using Markov Chain Monte Carlo methods and presented using the resulting posterior mean and 95% credibile interval (CrI). Findings In our baseline scenario, we estimated that the basic reproductive number for 2019-nCoV was 2·68 (95% CrI 2·47–2·86) and that 75 815 individuals (95% CrI 37 304–130 330) have been infected in Wuhan as of Jan 25, 2020. The epidemic doubling time was 6·4 days (95% CrI 5·8–7·1). We estimated that in the baseline scenario, Chongqing, Beijing, Shanghai, Guangzhou, and Shenzhen had imported 461 (95% CrI 227–805), 113 (57–193), 98 (49–168), 111 (56–191), and 80 (40–139) infections from Wuhan, respectively. If the transmissibility of 2019-nCoV were similar everywhere domestically and over time, we inferred that epidemics are already growing exponentially in multiple major cities of China with a lag time behind the Wuhan outbreak of about 1–2 weeks. Interpretation Given that 2019-nCoV is no longer contained within Wuhan, other major Chinese cities are probably sustaining localised outbreaks. Large cities overseas with close transport links to China could also become outbreak epicentres, unless substantial public health interventions at both the population and personal levels are implemented immediately. Independent self-sustaining outbreaks in major cities globally could become inevitable because of substantial exportation of presymptomatic cases and in the absence of large-scale public health interventions. Preparedness plans and mitigation interventions should be readied for quick deployment globally. Funding Health and Medical Research Fund (Hong Kong, China).",2020,"Wu, Joseph T.; Leung, Kathy; Leung, Gabriel M.",The Lancet,3003573988,#106,
,CZI,What next for the coronavirus response?,10.1016/S0140-6736(20)30292-0,,,,,2020,"Zarocostas, John",The Lancet,3005352349,#356,
,CZI,Offline: 2019-nCoV—“A desperate plea”,10.1016/S0140-6736(20)30299-3,,,,,2020,"Horton, Richard",The Lancet,,#407,
,CZI,What to do next to control the 2019-nCoV epidemic?,10.1016/S0140-6736(20)30300-7,,,,,2020,"Wang, Fu-Sheng; Zhang, Chao",The Lancet,3005057182,#367,
,CZI,"Department of Error: Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study (The Lancet (2020) 395(10225) (689–697), (S0140673620302609), (10.1016/S0140-6736(20)30260-9))",10.1016/S0140-6736(20)30302-0,,,,"Wu JT, Leung K, Leung GM. Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study. Lancet 2020; published online Jan 31. https://doi.org/10.1016/10.1016/S0140-6736(20)30260-9—In this Article, the data sharing statement has been amended to clarify the sources from which data can be obtained. This correction has been made to the online version as of Feb 4, 2020, and will be made to the printed version.",2020,,The Lancet,,#2997,
,CZI,Baricitinib as potential treatment for 2019-nCoV acute respiratory disease,10.1016/S0140-6736(20)30304-4,,,,,2020,"Richardson, Peter; Griffin, Ivan; Tucker, Catherine; Smith, Dan; Oechsle, Olly; Phelan, Anne; Stebbing, Justin",The Lancet,3004919484,#217,
,CZI,Reducing mortality from 2019-nCoV: host-directed therapies should be an option,10.1016/S0140-6736(20)30305-6,,,,,2020,"Zumla, Alimuddin; Hui, David S.; Azhar, Esam I.; Memish, Ziad A.; Maeurer, Markus",The Lancet,3004743633,#244,
,CZI,Full spectrum of COVID-19 severity still being depicted,10.1016/S0140-6736(20)30308-1,,,,,,"Xu, Zhou; Li, Shu; Tian, Shen; Li, Hao; Kong, Ling-quan",The Lancet,3006304557,#898,
,CZI,2019-nCoV epidemic: address mental health care to empower society,10.1016/S0140-6736(20)30309-3,,,,,,"Bao, Yanping; Sun, Yankun; Meng, Shiqiu; Shi, Jie; Lu, Lin",The Lancet,3005380688,#527,
,CZI,2019-nCoV epidemic: what about pregnancies?,10.1016/S0140-6736(20)30311-1,,,,,2020,"Favre, Guillaume; Pomar, Léo; Musso, Didier; Baud, David",The Lancet,3005113694,#411,
,CZI,2019-nCoV transmission through the ocular surface must not be ignored,10.1016/S0140-6736(20)30313-5,,,,,,"Lu, Cheng-wei; Liu, Xiu-fen; Jia, Zhi-fang",The Lancet,3005091255,#390,
,CZI,Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury,10.1016/S0140-6736(20)30317-2,,,,,,"Russell, Clark D.; Millar, Jonathan E.; Baillie, J. Kenneth",The Lancet,3005403371,#523,
,CZI,From Hendra to Wuhan: what has been learned in responding to emerging zoonotic viruses,10.1016/S0140-6736(20)30350-0,,,,,2020,"Wang, Lin-Fa; Anderson, Danielle E.; Mackenzie, John S.; Merson, Michael H.",The Lancet,3005787104,#721,
,CZI,Africa prepares for coronavirus,10.1016/S0140-6736(20)30355-X,,,,,2020,"Makoni, Munyaradzi",The Lancet,3006009475,#839,
,CZI,Early lessons from the frontline of the 2019-nCoV outbreak,10.1016/S0140-6736(20)30356-1,,,,,2020,"Zhang, Hong",The Lancet,3005675140,#711,
,CZI,"2019-nCoV, fake news, and racism",10.1016/S0140-6736(20)30357-3,,,,,2020,"Shimizu, Kazuki",The Lancet,3005716085,#731,
,CZI,Anti-Chinese sentiment during the 2019-nCoV outbreak,10.1016/S0140-6736(20)30358-5,,,,,2020,"Chung, Roger Yat-Nork; Li, Minnie Ming",The Lancet,3005805019,#787,
,CZI,Minimise nosocomial spread of 2019-nCoV when treating acute respiratory failure,10.1016/S0140-6736(20)30359-7,,,,,2020,"Cabrini, Luca; Landoni, Giovanni; Zangrillo, Alberto",The Lancet,3005875949,#793,
,CZI,Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records,10.1016/S0140-6736(20)30360-3,,,,"Summary Background Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Limited data are available for pregnant women with COVID-19 pneumonia. This study aimed to evaluate the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection. Methods Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for nine pregnant women with laboratory-confirmed COVID-19 pneumonia (ie, with maternal throat swab samples that were positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan 20 to Jan 31, 2020. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation. Findings All nine patients had a caesarean section in their third trimester. Seven patients presented with a fever. Other symptoms, including cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia (<1·0 × 10⁹ cells per L). Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died, as of Feb 4, 2020. Nine livebirths were recorded. No neonatal asphyxia was observed in newborn babies. All nine livebirths had a 1-min Apgar score of 8–9 and a 5-min Apgar score of 9–10. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus. Interpretation The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy. Funding Hubei Science and Technology Plan, Wuhan University Medical Development Plan.",2020,"Chen, Huijun; Guo, Juanjuan; Wang, Chen; Luo, Fan; Yu, Xuechen; Zhang, Wei; Li, Jiafu; Zhao, Dongchi; Xu, Dan; Gong, Qing; Liao, Jing; Yang, Huixia; Hou, Wei; Zhang, Yuanzhen",The Lancet,3005679569,#789,
,CZI,On the use of corticosteroids for 2019-nCoV pneumonia,10.1016/S0140-6736(20)30361-5,,,,,2020,"Shang, Lianhan; Zhao, Jianping; Hu, Yi; Du, Ronghui; Cao, Bin",The Lancet,3005905966,#733,
,CZI,Offline: How to defeat political populism,10.1016/S0140-6736(20)30363-9,,,,,2020,"Horton, Richard",The Lancet,3005799376,#842,
,CZI,What are the risks of COVID-19 infection in pregnant women?,10.1016/S0140-6736(20)30365-2,,,,,2020,"Qiao, Jie",The Lancet,3006304225,#741,
,CZI,"First imported case of 2019 novel coronavirus in Canada, presenting as mild pneumonia",10.1016/S0140-6736(20)30370-6,,,,,2020,"Silverstein, William Kyle; Stroud, Lynfa; Cleghorn, Graham Edward; Leis, Jerome Allen",The Lancet,3006411443,#836,
,CZI,Full spectrum of COVID-19 severity still being depicted &#x2013; Authors' reply,10.1016/S0140-6736(20)30371-8,,,,,,"Gu, Xiaoying; Cao, Bin; Wang, Jianwei",The Lancet,3006017470,#978,
,CZI,Do not violate the International Health Regulations during the COVID-19 outbreak,10.1016/S0140-6736(20)30373-1,,,,,2020,"Habibi, Roojin; Burci, Gian Luca; de Campos, Thana C.; Chirwa, Danwood; Cinà, Margherita; Dagron, Stéphanie; Eccleston-Turner, Mark; Forman, Lisa; Gostin, Lawrence O.; Meier, Benjamin Mason; Negri, Stefania; Ooms, Gorik; Sekalala, Sharifah; Taylor, Allyn; Yamin, Alicia Ely; Hoffman, Steven J.",The Lancet,3006304371,#845,
,CZI,COVID-19: what is next for public health?,10.1016/s0140-6736(20)30374-3,,,,"The WHO Scientific and Technical Advisory Group for Infectious Hazards (STAG-IH), working with the WHO secretariat, reviewed available information about the outbreaks of 2019 novel coronavirus disease (COVID-19) on Feb 7, 2020, in Geneva, Switzerland, and concluded that the continuing strategy of containment for elimination should continue, and that the coming 2–3 weeks through to the end of February, 2020, will be crucial to monitor the situation of community transmission to update WHO public health recommendations if required.",2020,"Heymann, David L.; Shindo, Nahoko; Bedford, Juliet; Enria, Delia; Giesecke, Johan; Heymann, David; Ihekweazu, Chikwe; Kobinger, Gary; Lane, Clifford; Memish, Ziad; Myoung-don, Oh; Sall, Amadou Alpha; Ungchusak, Kum; Wieler, Lothar; Infect, W. H. O. Sci Tech Advisory Grp",Lancet,3005995896,#3637,
,CZI,COVID-19 Update From China,10.1016/S0140-6736(20)30375-5,,,,"By mid-February 2020 there were 60,000 confirmed cases of COVID-19, the vast majority diagnosed in Hubei Province (including Wuhan city) in mainland China. China CDC Chief Epidemiologist Zunyou Wu, MD, PhD discusses the latest COVID-19 developments in the country with JAMA Editor in Chief Howard Bauchner, MD.",2020,JAMA,JAMA,3005550222,#887,
,CZI,Timely research papers about COVID-19 in China,10.1016/S0140-6736(20)30375-5,,,,,,"Xiang, Yu-Tao; Li, Wen; Zhang, Qinge; Jin, Yu; Rao, Wen-Wang; Zeng, Liang-Nan; Lok, Grace K. I.; Chow, Ines H. I.; Cheung, Teris; Hall, Brian J.",The Lancet,3005550222,#1088,
,CZI,COVID-19: fighting panic with information,10.1016/S0140-6736(20)30379-2,,,,,2020,"The, Lancet",The Lancet,3006304371,#1357,
,CZI,Offline: Facts are not enough,10.1016/S0140-6736(20)30405-0,,,,,2020,"Horton, Richard",The Lancet,2035283980,#1628,
,CZI,Preparedness and vulnerability of African countries against importations of COVID-19: a modelling study,10.1016/S0140-6736(20)30411-6,,,,,2020,"Marius Gilbert, Giulia Pullano, Francesco Pinotti, Eugenio Valdano, Chiara Poletto, Pierre-Yves Boëlle, Eric D’Ortenzio, Yazdan Yazdanpanah,; Serge Paul Eholie, Mathias Altmann, Bernardo Gutierrez, Moritz U G Kraemer, Vittoria Colizza",The Lancet,3004759370,#1335,
,CZI,"Statement in support of the scientists, public health professionals, and medical professionals of China combatting COVID-19",10.1016/S0140-6736(20)30418-9,,,,,2020,"Calisher, Charles; Carroll, Dennis; Colwell, Rita; Corley, Ronald B.; Daszak, Peter; Drosten, Christian; Enjuanes, Luis; Farrar, Jeremy; Field, Hume; Golding, Josie; Gorbalenya, Alexander; Haagmans, Bart; Hughes, James M.; Karesh, William B.; Keusch, Gerald T.; Lam, Sai Kit; Lubroth, Juan; Mackenzie, John S.; Madoff, Larry; Mazet, Jonna; Palese, Peter; Perlman, Stanley; Poon, Leo; Roizman, Bernard; Saif, Linda; Subbarao, Kanta; Turner, Mike",The Lancet,2287268028,#1326,
,CZI,Scientists are sprinting to outpace the novel coronavirus,10.1016/S0140-6736(20)30420-7,,,,,2020,"Ghebreyesus, Tedros Adhanom; Swaminathan, Soumya",The Lancet,2314463002,#1846,
,CZI,COVID-19 control in China during mass population movements at New Year,10.1016/S0140-6736(20)30421-9,,,,"Government policies enacted during the Chinese Lunar New Year holiday are likely to have helped reduce the spread of the virus by decreasing contact and increasing physical distance between those who have COVID-19 and those who do not. As part of these social distancing policies, the Chinese Government encouraged people to stay at home; discouraged mass gatherings; cancelled or postponed large public events; and closed schools, universities, government offices, libraries, museums, and factories. Only limited segments of urban public transport systems remained operational and all cross-province bus routes were taken out of service. As a result of these policies and public information and education campaigns, Chinese citizens started to take measures to protect themselves against COVID-19, such as staying at home as far as possible, limiting social contacts, and wearing protective masks when they needed to move in public.",,"Chen, Simiao; Yang, Juntao; Yang, Weizhong; Wang, Chen; Bärnighausen, Till",The Lancet,1220324463,#2005,
,CZI,The danger of stories in global health,10.1016/S0140-6736(20)30427-X,,,,,2020,"Harman, Sophie",The Lancet,2896599320,#4565,
,CZI,Indian pharma threatened by COVID-19 shutdowns in China,10.1016/S0140-6736(20)30459-1,,,,"As factories in China are closed, India is working to maintain supplies of active pharmaceutical ingredients. Patralekha Chatterjee reports from New Delhi. India supplies low-cost generic drugs to millions of people, both within and outside the country. But Indian pharmaceutical companies procure almost 70% of the active pharmaceutical ingredients (APIs) for their medicines from China, the world's leading producer and exporter of APIs by volume. As factories in China are closed to try to stem the coronavirus disease 2019 outbreak, pharmaceutical companies and the Indian Government are becoming concerned over the vulnerability of the Indian pharmaceutical supply chain.",2020,"Chatterjee, Patralekha",The Lancet,819170924,#2755,
,CZI,The psychological impact of quarantine and how to reduce it: rapid review of the evidence,10.1016/S0140-6736(20)30460-8,,,,"The December, 2019 coronavirus disease outbreak has seen many countries ask people who have potentially come into contact with the infection to isolate themselves at home or in a dedicated quarantine facility. Decisions on how to apply quarantine should be based on the best available evidence. We did a Review of the psychological impact of quarantine using three electronic databases. Of 3166 papers found, 24 are included in this Review. Most reviewed studies reported negative psychological effects including post-traumatic stress symptoms, confusion, and anger. Stressors included longer quarantine duration, infection fears, frustration, boredom, inadequate supplies, inadequate information, financial loss, and stigma. Some researchers have suggested long-lasting effects. In situations where quarantine is deemed necessary, officials should quarantine individuals for no longer than required, provide clear rationale for quarantine and information about protocols, and ensure sufficient supplies are provided. Appeals to altruism by reminding the public about the benefits of quarantine to wider society can be favourable.",,"Brooks, Samantha K.; Webster, Rebecca K.; Smith, Louise E.; Woodland, Lisa; Wessely, Simon; Greenberg, Neil; Rubin, Gideon James",The Lancet,3006659024,#2354,
,CZI,How to fight an infodemic,10.1016/S0140-6736(20)30461-X,,,,"WHO's newly launched platform aims to combat misinformation around COVID-19. John Zarocostas reports from WHO is leading the effort to slow the spread of the 2019 coronavirus disease (COVID-19) outbreak. But a global epidemic of misinformation—spreading rapidly through social media platforms and other outlets—poses a serious problem for public health. “We’re not just fighting an epidemic; we’re fighting an infodemic”, said WHO Director-General Tedros Adhanom Ghebreyesus at the Munich Security Conference on Feb 15. Immediately after COVID-19 was declared a Public Health Emergency of International Concern, WHO's risk communication team launched a new information platform called WHO Information Network for Epidemics (EPI-WIN), with the aim of using a series of amplifiers to share tailored information with specific target groups. Sylvie Briand, director of Infectious Hazards Management at WHO's Health Emergencies Programme and architect of WHO's strategy to counter the infodemic risk, told The Lancet, “We know that every outbreak will be accompanied by a kind of tsunami of information, but also within this information you always have misinformation, rumours, etc. We know that even in the Middle Ages there was this phenomenon”. “But the difference now with social media is that this phenomenon is amplified, it goes faster and further, like the viruses that travel with people and go faster and further. So it is a new challenge, and the challenge is the [timing] because you need to be faster if you want to fill the void…What is at stake during an outbreak is making sure people will do the right thing to control the disease or to mitigate its impact. So it is not only information to make sure people are informed; it is also making sure people are informed to act appropriately.” About 20 staff and some consultants are involved in WHO's communications teams globally, at any given time. This includes social media personnel at each of WHO's six regional offices, risk communications consultants, and WHO communications officers.",2020,"Zarocostas, John",The Lancet,2799474450,#3015,
,CZI,Secondary attack rate and superspreading events for SARS-CoV-2,10.1016/S0140-6736(20)30462-1,,,,,2020,"Liu, Yang; Eggo, Rosalind M.; Kucharski, Adam J.",The Lancet,2121671559,#2593,
,CZI,Lessons for managing high-consequence infections from first COVID-19 cases in the UK,10.1016/S0140-6736(20)30463-3,,,,"These first UK cases of COVID-19 raise important points about the management of cases of HCID in England. The decision to test for SARS-CoV-2 is based on a clinical and epidemiological case definition, and testing is only approved if this is met. When tested, neither of these people clearly met the current case definition, and had criteria been strictly applied, testing might not have been done. A decision to test was made because of high clinical suspicion and in response to latest available information about the distribution of infection. It is important that testing is appropriately targeted, and this is best done by applying clear case definitions. However, with any newly emerging infection, case definitions must evolve rapidly as information accrues. There should also be room for flexibility on the basis of discussion with clinical and public health experts",,"Moss, Peter; Barlow, Gavin; Easom, Nicholas; Lillie, Patrick; Samson, Anda",The Lancet,2217820961,#2702,
,CZI,"Looming threat of COVID-19 infection in Africa: act collectively, and fast",10.1016/S0140-6736(20)30464-5,,,,"Models that enable the continent to better allocate scarce resources to better prepare and respond to the COVID-19 epidemic are crucial. The modelling study by Marius Gilbert and colleagues in The Lancet identifies each African country's risk of importation of COVID-19 from China, using data on the volume of air travel from three airports in provinces in China to African countries. Gilbert and colleagues use two indicators to determine the capacity of countries to detect and respond to cases: preparedness, using the WHO International Health Regulations Monitoring and Evaluation Framework; and vulnerability, using the Infectious Disease Vulnerability Index. Based on their analysis, Egypt, Algeria, and South Africa had the highest importation risk, and a moderate to high capacity to respond to outbreaks. Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, and Kenya had moderate risk with variable capacity and high vulnerability. In the model, the risk mainly originates from Guangdong, Fujian, and Beijing. The study provides a valuable tool that can help countries in Africa prioritise and allocate resources as they prepare to respond to the potential introduction and spread of COVID-19.",,"Nkengasong, John N.; Mankoula, Wessam",The Lancet,3006304225,#2701,
,CZI,COVID-19: preparing for superspreader potential among Umrah pilgrims to Saudi Arabia,10.1016/S0140-6736(20)30466-9,,,,"The ongoing coronavirus disease 2019 (COVID-19) outbreak is a Public Health Emergency of International Concern (PHEIC), and the emergence of new epicentres of spread, such as South Korea and Iran, besides Wuhan, China, should draw attention to potential superspreader events.Of concern is the continuous Umrah pilgrimage to Saudi Arabia by Muslim pilgrims from more than 180 countries. In addition to the non-pilgrim air traffic (39 million people in 2018), Saudi Arabia received 7·5 million Umrah visa holders in 2019",,"Ebrahim, Shahul H.; Memish, Ziad A.",The Lancet,2074979691,#2703,
,CZI,COVID-19 and the anti-lessons of history,10.1016/S0140-6736(20)30468-2,,,,"As the outbreak of coronavirus disease 2019 (COVID-19) in China's Hubei province continues and new cases of the disease increase globally,1 there is pressure on historians to show the value of history for policy. How can the past assist in the real-time management of the crisis? What insights can be gleaned from the ongoing epidemic for future disease preparedness and prevention? Lurking in the background of these interrogatives is a more or less explicit accusation: why haven't past lessons been learned? The gist of some commentaries seems to be: “there is almost nothing surprising about this pandemic”.2 The history-as-lessons approach pivots on the assumption that epidemics are structurally comparable events, wherever and whenever they take place. The COVID-19 outbreak “creates a sense of déjà vu” with the 2003 outbreak of severe acute respiratory syndrome (SARS).3 Citing early estimates of the disease's infectiousness, based on an analysis of the first 425 confirmed cases in Wuhan,4 comparisons have been drawn with the 1918–19 influenza pandemic.5 Although in some respects the outbreak of COVID-19 presents a compelling argument for why history matters, there are problems with analogical views of the past because they constrain our ability to grasp the complex place-and-time-specific variables that drive contemporary disease emergence. A lessons approach to epidemics produces what Kenneth Burke, borrowing from the economist and sociologist Thorstein Veblen, called “trained incapacity”—“that state of affairs whereby one's very abilities can function as blindnesses”.6 Habitual modes of thinking can diminish our capacity to make lateral connections. When the present is viewed through the lens of former disease outbreaks, we typically focus on similitudes and overlook important differences. In other words, analogies create blind spots. As Burke commented, “a way of seeing is also a way of not seeing—a focus on object A involves a neglect of object B”.",,"Peckham, Robert",The Lancet,2116636416,#3136,
,CZI,The response of Milan's Emergency Medical System to the COVID-19 outbreak in Italy,10.1016/S0140-6736(20)30493-1,,,,"The number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), is dramatically increasing worldwide.The first person-to-person transmission in Italy was reported on Feb 21, 2020, and led to an infection chain that represents the largest COVID-19 outbreak outside Asia to date. Here we document the response of the Emergency Medical System (EMS) of the metropolitan area of Milan, Italy, to the COVID-19 outbreak.On Jan 30, 2020, WHO declared the COVID-19 outbreak a public health emergency of international concern.2 Since then, the Italian Government has implemented extraordinary measures to restrict viral spread, including interruptions of air traffic from China, organised repatriation flights and quarantines for Italian travellers in China, and strict controls at international airports' arrival terminals. Local medical authorities adopted specific WHO recommendations to identify and isolate suspected cases of COVID-19.Such recommendations were addressed to patients presenting with respiratory symptoms and who had travelled to an endemic area in the previous 14 days or who had worked in the health-care sector, having been in close contact with patients with severe respiratory disease with unknown aetiology. Suspected cases were transferred to preselected hospital facilities where the SARS-CoV-2 test was available and infectious disease units were ready for isolation of confirmed cases.",,"Spina, Stefano; Marrazzo, Francesco; Migliari, Maurizio; Stucchi, Riccardo; Sforza, Alessandra; Fumagalli, Roberto",The Lancet,2050082093,#2989,
,CZI,Mass masking in the COVID-19 epidemic: people need guidance,10.1016/S0140-6736(20)30520-1,,,,"WHO recommends against wearing masks in community settings because of lack of evidence.2 However, absence of evidence of effectiveness should not be equated to evidence of ineffectiveness, especially when facing a novel situation with limited alternative options. It has long been recommended that for respiratory infections like influenza, affected patients should wear masks to limit droplet spread. If everyone puts on a mask in public places, it would help to remove stigmatisation that has hitherto discouraged masking of symptomatic patients in many places.3 Furthermore, transmission from asymptomatic infected individuals has been documented for COVID-19, and viral load is particularly high at early disease stage.4 , 5 Masking, as a public health intervention, would probably intercept the transmission link and prevent these apparently healthy infectious sources.",,"Leung, Chi Chiu; Lam, Tai Hing; Cheng, Kar Keung",The Lancet,3006419170,#3483,
,CZI,Has China faced only a herald wave of SARS-CoV-2?,10.1016/S0140-6736(20)30521-3,,,,"The attack rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) calculated by mathematical models, from estimates of the basic reproduction number, R0, of 2–3, suggests that 50–60% of the population should eventually be infected because the population seems to be entirely naive to the new virus.1 The observed attack rate on board the Diamond Princess cruise ship remained slightly below 20% (705 of 3711 passengers and crew members became infected).1 It is of upmost importance to know whether the SARS-CoV-2 outbreak in China is subsiding, as local authorities and the entire international community might wish. With 80 026 COVID-19 cases officially reported from China as of March 2, 2020,2 the proportion of the population affected remains far from 50%, or even 20%, of China's 1·4 billion people. Has China just experienced a herald wave, to use terminology borrowed from those who study tsunamis, and is the big wave still to come? Serosurveys can help answer these questions precisely.3 To serosurvey the outbreak would involve testing sera of blood samples from the most representative sample of the population at the epicentre of the epidemic, Wuhan. Serology analysis with neutralising antibodies from the 1000 people could allow for the rate of SARS-CoV-2 infections to be estimated with good accuracy. This rate could be extrapolated to the city's entire population and thus inform more precisely whether the provisional attack rate during this period was a few cases per thousand or perhaps affected 1–2% of the population, 20%, or more. Serosurveys should be seen as polls before elections; they can be repeated several times,3 week after week, to monitor the epidemic precisely. There is no reason to wait for the end of the epidemic before doing serosurveys. The results would be tremendously informative to China, first and foremost, and to the entire international community, on the risk of big secondary epidemic waves",,"Flahault, Antoine",The Lancet,3006355661,#4102,
,CZI,"COVID-19: too little, too late?",10.1016/S0140-6736(20)30522-5,,,,,2020,"The, Lancet",The Lancet,2519393586,#4430,
,CZI,COVID-19: the gendered impacts of the outbreak,10.1016/S0140-6736(20)30526-2,,,,"Policies and public health efforts have not addressed the gendered impacts of disease outbreaks.1 The response to coronavirus disease 2019 (COVID-19) appears no different. We are not aware of any gender analysis of the outbreak by global health institutions or governments in affected countries or in preparedness phases. Recognising the extent to which disease outbreaks affect women and men differently is a fundamental step to understanding the primary and secondary effects of a health emergency on different individuals and communities, and for creating effective, equitable policies and interventions. Although sex-disaggregated data for COVID-19 show equal numbers of cases between men and women so far, there seem to be sex differences in mortality and vulnerability to the disease.2 Emerging evidence suggests that more men than women are dying, potentially due to sex-based immunological3 or gendered differences, such as patterns and prevalence of smoking.4 However, current sex-disaggregated data are incomplete, cautioning against early assumptions. Simultaneously, data from the State Council Information Office in China suggest that more than 90% of health-care workers in Hubei province are women, emphasising the gendered nature of the health workforce and the risk that predominantly female health workers incur.",,"Wenham, Clare; Smith, Julia; Morgan, Rosemary",The Lancet,3006304371,#5424,
,CZI,Mitigate the effects of home confinement on children during the COVID-19 outbreak,10.1016/S0140-6736(20)30547-X,,,,"In response to the coronavirus disease 2019 (COVID-19) outbreak, the Chinese Government has ordered a nationwide school closure as an emergency measure to prevent spreading of the infection. Public activities are discouraged. The Ministry of Education estimates that more than 220 million children and adolescents are confined to their homes; this includes 180 million primary and secondary students and 47 million preschool children).1 Thanks to the strong administrative system in China, the emergency home schooling plan has been rigorously implemented.2 Massive efforts are being made by schools and teachers at all levels to create online courses and deliver them through TV broadcasts and the internet in record time. The new virtual semester has just started in many parts of the country, and various courses are offered online in a well organised manner. These actions are helping to alleviate many parents' concerns about their children's educational attainment by ensuring that school learning is largely undisrupted. Although these measures and efforts are highly commendable and necessary, there are reasons to be concerned because prolonged school closure and home confinement during a disease outbreak might have negative effects on children's physical and mental health.3 , 4 Evidence suggests that when children are out of school (eg, weekends and summer holidays), they are physically less active, have much longer screen time, irregular sleep patterns, and less favourable diets, resulting in weight gain and a loss of cardiorespiratory fitness.3 , 5 Such negative effects on health are likely to be much worse when children are confined to their homes without outdoor activities and interaction with same aged friends during the outbreak.",,"Wang, Guanghai; Zhang, Yunting; Zhao, Jin; Zhang, Jun; Jiang, Fan",The Lancet,1968779433,#4165,
,CZI,Are high-performing health systems resilient against the COVID-19 epidemic?,10.1016/S0140-6736(20)30551-1,,,,"As of March 5, 2020, there has been sustained local transmission of coronavirus disease 2019 (COVID-19) in Hong Kong, Singapore, and Japan.1 Containment strategies seem to have prevented smaller transmission chains from amplifying into widespread community transmission. The health systems in these locations have generally been able to adapt,2 , 3 but their resilience could be affected if the COVID-19 epidemic continues for many more months and increasing numbers of people require services. We outline some of the core dimensions of these resilient health systems4 and their responses to the COVID-19 epidemic. First, after variable periods of adaptation, the three locations took actions to manage the outbreak of a new pathogen. Surveillance systems were readjusted to identify potential cases while public health staff identified their contacts. National laboratory networks developed diagnostic tests once the COVID-19 genetic sequences were published5 and laboratory testing capacity was increased in all three locations, although expansion of the diagnostic capacity to university and large private laboratories in Japan is still ongoing. In Hong Kong, initially, only pneumonia patients without a microbiological diagnosis were tested, but surveillance has been broadened to include all inpatients with pneumonia and a purposively sampled proportion of outpatients and emergency attendees totalling about 1500 per day (Leung GM, unpublished). Japan's testing strategy has also evolved with diagnostic tests now offered to all suspected cases irrespective of their travel history; however, there are reports of cases that should have been tested but were not.",,"Legido-Quigley, Helena; Asgari, Nima; Teo, Yik Ying; Leung, Gabriel M.; Oshitani, Hitoshi; Fukuda, Keiji; Cook, Alex R.; Hsu, Li Yang; Shibuya, Kenji; Heymann, David",The Lancet,2980700437,#5422,
,CZI,SARS-CoV-2 is an appropriate name for the new coronavirus,10.1016/S0140-6736(20)30557-2,,,,"We have read with great interest the Correspondence by Shibo Jiang and colleagues,1 in which they propose a name change for the newly emerged coronavirus,2 which was recently designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses.3 The authors argued that the use of SARS in the virus name could confuse the public about the disease that it causes; in addition, they noted that the name SARS-CoV-2 is not consistent with the disease name chosen by WHO, coronavirus disease 2019. The authors also indicated that scientifically, SARS-CoV-2 is naturally occurring and different from other SARS-like or SARS-related coronaviruses that are mainly characterised by their genome sequences. Furthermore, given the probability of future attenuation of this virus to a low-pathogenic form, the authors predict that the use of the name SARS-CoV-2 might have adverse effects, both socially and economically. On these grounds, the authors suggest that the name of the new virus is changed to human coronavirus 2019 (HCoV-19). Although these concerns and suggestions are appreciated, we feel that the adoption of SARS-CoV-2 by the Coronavirus Study Group was appropriate. To facilitate good practice and scientific exchange, the International Committee on Taxonomy of Viruses has established standardised formats for classifying viruses. Under these rules, a newly emerged virus is normally assigned to a species based on phylogeny and taxonomy.4 Through DivErsity pArtitioning by hieRarchical Clustering-based analyses,5 the newly emerged coronavirus was deemed not sufficiently novel but is a sister virus to SARS-CoV, the primary viral isolate defining the species. The SARS-CoV species includes viruses such as SARS-CoV, SARS-CoV_PC4-227, and SARSr-CoV-btKY72. SARS-CoV-2 is the newest member of this viral species. The use of SARS in naming SARS-CoV-2 does not derive from the name of the SARS disease but is a natural extension of the taxonomic practice for viruses in the SARS species. The use of SARS for viruses in this species mainly refers to their taxonomic relationship to the founding virus of this species, SARS-CoV. In other words, viruses in this species can be named SARS regardless of whether or not they cause SARS-like diseases.",,"Wu, Yuntao; Ho, Wenzhe; Huang, Yaowei; Jin, Dong-Yan; Li, Shiyue; Liu, Shan-Lu; Liu, Xuefeng; Qiu, Jianming; Sang, Yongming; Wang, Qiuhong; Yuen, Kwok-Yung; Zheng, Zhi-Ming",The Lancet,2047323912,#5425,
,CZI,Coronavirus spreads,10.1016/S0262-4079(20)30188-3,,,,"The deadly virus that emerged in Wuhan, China, may be much more contagious than initially thought. Jessica Hamzelou reports",2020,"Hamzelou, Jessica",New Scientist,3002306895,#145,
,CZI,Viruses from animals,10.1016/S0262-4079(20)30236-0,,,,Infections that cross over from other species are a deadly problem,2020,"Le Page, Michael",New Scientist,3003282835,#500,
,CZI,How bad will it get?,10.1016/S0262-4079(20)30278-5,,,,"While the coronavirus death rate may be lower than some estimates, case numbers may be far higher, reports Debora MacKenzie",2020,"MacKenzie, Debora",New Scientist,3005843255,#944,
,CZI,Wuhan-like virus discovered seven years ago,10.1016/S0262-4079(20)30281-5,,,,,2020,"MacKenzie, Debora",New Scientist,3006474128,#943,
,CZI,Is it super-spreading?,10.1016/S0262-4079(20)30375-4,,,,"If the covid-19 virus is transmitted largely by superspreaders, it might not go pandemic, reports Debora MacKenzie",2020,"MacKenzie, Debora",New Scientist,2078552808,#1553,
,CZI,Drug trials under way,10.1016/S0262-4079(20)30376-6,,,,"We'll soon know if covid-19 can be treated with drugs developed for HIV and Ebola, reports Alice Klein",2020,"Klein, Alice",New Scientist,2888181989,#1605,
,CZI,Will heat kill the coronavirus?,10.1016/S0262-4079(20)30377-8,,,,"We don't know if changing seasons will help stem the outbreak, says Michael Le Page",2020,"Le Page, Michael",New Scientist,2989729408,#1596,
,CZI,China uses mass surveillance tech to fight spread of coronavirus,10.1016/S0262-4079(20)30378-X,,,,,2020,"Lu, Donna",New Scientist,2792118424,#1808,
,CZI,Calculating virus spread,10.1016/S0262-4079(20)30402-4,,,,"Getting a full picture of the coronavirus outbreak is extremely difficult. Maths can help plug some of the gaps, says Adam Kucharski",2020,"Kucharski, Adam",New Scientist,3006474128,#1600,
,CZI,Covid-19 spreads in US,10.1016/S0262-4079(20)30472-3,,,,Multiple outbreaks worldwide have led to countries stepping up their responses. By Debora MacKenzie and Press Association,2020,"MacKenzie, Debora; Association, Press",New Scientist,2113767588,#4881,
,CZI,How well prepared are we?,10.1016/S0262-4079(20)30473-5,,,,"Covid-19 is rapidly spreading around the world during a period when many healthcare systems are already under pressure, reports Debora MacKenzie",2020,"MacKenzie, Debora",New Scientist,753948547,#4880,
,CZI,"We were warned, so why couldn't we prevent it?",10.1016/S0262-4079(20)30476-0,,,,"SARS and MERS gave us ample warning of the risk of new coronaviruses, but we failed to set up sufficient defences, reports Debora MacKenzie",2020,"MacKenzie, Debora",New Scientist,1983232861,#4879,
,CZI,World braces for economic impact,10.1016/S0262-4079(20)30477-2,,,,"The repercussions for businesses, workers and supply chains could be severe",2020,"Vaughan, Adam",New Scientist,3005609763,#5499,
,CZI,A correlation study ofCT and clinical features of different clinical types of 2019 novel coronavirus pneumonia,10.1016/s0618-8278(19)30533-x,,,,"Objective To investigate the CT and clinical features of 2019 novel coronavirus (NCP) pneumonia. Methods Chest CT and clinical data of confirmed 103 patients with 2019 novel coronavirus pneumonia in January 2020, retrospectively. According to diagnosis and treatment of NCP infected pneumonia (trial version 5), all the patients were classified into mild( n =58), severe ( n =36) and very severe ( n =9) type, and their clinical findings, laboratory examination and CT finding were analyzed. CT features included lesions&rsquo; distribution, location, size, shape, edge, number, density, percentage of pneumonia lesions of the whole lung and extra-pulmonary manifestations. The CT features of different clinical subtypes were compared using &chi; 2 test or Fisher's exact probability. Comparisons between the percentage of pneumonic lesions to total lung volume were computed by using analysis of variance (normal distribution) or Kruskal-Wallis rank sum test (non-normal distribution). Results In terms of clinical manifestations, the patients with severe NCP were more common in elderly men, with a median age of 65 years. Fever was the first symptom in 49 (84%) of 58 patients with NCP, and fever was the first symptom in both severe and critical NCP patients. The incidence of cough in severe (25 / 36, 69%) and critical (6 /9, 67%) NCP patients was higher than that in general (20 /58, 34%). All critical patients have dyspnea. In terms of CT findings, common NCP showed double lung (40/58,71%) multiple (40 / 58,69%) ground glass (31/58,52%) or mixed (25 / 58,43%) lesions (56 / 58,97%); severe and critical NCP showed double lung lesions, heavy NCP mainly showed multiple (34 / 36,96%) patches (33 / 36,92%) mixed density lesions (26 / 36,72%); 9 severe NCP lesions were more than 3 cm Mixed density lesions. The percentage of pneumonia focus in the whole lung volume: the common type (12.5% &plusmn; 6.1%) was significantly lower than the severe type (25.9% &plusmn; 10.7%) and the critical type (47.2% &plusmn; 19.2%) NCP, the difference was statistically significant ( P values were &lt; 0.001 and 0.002 respectively), and the severe type NCP was also significantly lower than the critical type ( P = 0.032). Conclusions CT and clinical features of different clinical types of NCP pneumonia are different. Chest CT findings have unique characteristic, which can not only make early diagnosis, but also evaluate its clinical course and severity.",2020,"HUANG, Lu; HAN, Rui; YU, Pengxin; WANG, Shaokang; XIA, Liming",Chinese Journal of Radiology,2937473538,#2257,
,CZI,Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China,10.1016/S1470-2045(20)30096-6,,,,,2020,"Liang, Wenhua; Guan, Weijie; Chen, Ruchong; Wang, Wei; Li, Jianfu; Xu, Ke; Li, Caichen; Ai, Qing; Lu, Weixiang; Liang, Hengrui; Li, Shiyue; He, Jianxing",The Lancet Oncology,3006355661,#951,
,CZI,Risk of COVID-19 for patients with cancer,10.1016/S1470-2045(20)30149-2,,,,"The authors concluded by use of epidemiological statistics that because the proportion of patients with cancer histories was higher in a cohort with COVID-19 than in the population in China, patients with cancer were more likely to develop COVID-19. They found 18 COVID-19 patients with cancer histories among 1590 COVID-19 patients from 575 hospitals in 31 provincial regions. Of these 16 patients (two of the 18 patients had unknown treatment status), only four had undergone surgery or chemotherapy within the previous month; 12 had recovered from initial cancer treatments (eg, surgery or chemotherapy) and had no obvious immunosuppression. We therefore do not think the COVID-19 infections in the 12 survivors of previous cancers were associated with their cancers. COVID-19 is a highly contagious infection to which everyone, to our knowledge, is susceptible; the most important morbidity factor is exposure to an infection source.2 Furthermore, although the authors indicate that patients with cancer had worse outcomes from COVID-19, they also reported the median age of these patients (63·1 years) to be significantly higher than for those without cancer (48·7 years), suggesting that older age is associated with worse COVID-19 outcomes",,"Wang, Hanping; Zhang, Li",The Lancet Oncology,2600570919,#3482,
,CZI,Risk of COVID-19 for cancer patients,10.1016/S1470-2045(20)30150-9,,,,"We read the excellent Comment by Wenhua Liang and colleagues1 in The Lancet Oncology with great interest. Of 1590 cases with confirmed coronavirus disease 2019 (COVID-19), 18 patients had a history of cancer. The authors concluded that patients with cancer had a higher risk of COVID-19 and with a poorer prognosis than those without cancer. First, the data in the Comment by Liang and colleagues1 showed a higher percentage of patients with cancer in the COVID-19 cohort than in the overall population. However, this observation is not sufficient to conclude that patients with cancer had a higher risk of COVID-19. The incidence of COVID-19 in patients with cancer would be more informative in assessing whether or not patients with cancer have an increased risk of COVID-19. Second, we reviewed the cancer history of the 18 individuals discussed in Liang and colleagues' Comment.1 We are concerned that such a small sample size with a large amount of heterogeneity, presenting as various cancer types with different biological behaviours, highly variable disease courses (from 0–16 years), and diverse treatment strategies, might be filled with contingency and thus not ideally representative of the whole population with cancer. Notably, half of the patients with cancer had a disease course of more than 4 years, indicating that a substantial proportion of these patients might be clinically cured.",,"Xia, Yang; Jin, Rui; Zhao, Jing; Li, Wen; Shen, Huahao",The Lancet Oncology,2947157398,#3481,
,CZI,Game consumption and the 2019 novel coronavirus,10.1016/S1473-3099(20)30063-3,,,,,,"Li, Jie; Li, Jun; Xie, Xiaoru; Cai, Xiaomei; Huang, Jian; Tian, Xuemei; Zhu, Hong",The Lancet Infectious Diseases,3005031775,#515,
,CZI,The first 2019 novel coronavirus case in Nepal,10.1016/S1473-3099(20)30067-0,,,,,2020,"Bastola, Anup; Sah, Ranjit; Rodriguez-Morales, Alfonso J.; Lal, Bibek Kumar; Jha, Runa; Ojha, Hemant Chanda; Shrestha, Bikesh; Chu, Daniel K. W.; Poon, Leo L. M.; Costello, Anthony; Morita, Kouichi; Pandey, Basu Dev",The Lancet Infectious Diseases,3004634239,#628,
,CZI,Pandemic potential of 2019-nCoV,10.1016/S1473-3099(20)30068-2,,,,,2020,"Thompson, Robin",The Lancet Infectious Diseases,3004907789,#514,
,CZI,Correction to Lancet Infect Dis 2019; 20: 275–76,10.1016/S1473-3099(20)30071-2,,,,,2020,,The Lancet Infectious Diseases,,#2468,
,CZI,Challenges of coronavirus disease 2019,10.1016/S1473-3099(20)30072-4,,,,,,"The Lancet Infectious, Diseases",The Lancet Infectious Diseases,2981418129,#1103,
,CZI,Outbreak of coronavirus disease 2019,10.1016/S1473-3099(20)30076-1,,,,,,"Burki, Talha",The Lancet Infectious Diseases,3006609801,#1163,
,CZI,"Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study",10.1016/S1473-3099(20)30086-4,,,,"Summary Background A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were successively reported in Wuhan, China. We aimed to describe the CT findings across different timepoints throughout the disease course. Methods Patients with COVID-19 pneumonia (confirmed by next-generation sequencing or RT-PCR) who were admitted to one of two hospitals in Wuhan and who underwent serial chest CT scans were retrospectively enrolled. Patients were grouped on the basis of the interval between symptom onset and the first CT scan: group 1 (subclinical patients; scans done before symptom onset), group 2 (scans done ≤1 week after symptom onset), group 3 (>1 week to 2 weeks), and group 4 (>2 weeks to 3 weeks). Imaging features and their distribution were analysed and compared across the four groups. Findings 81 patients admitted to hospital between Dec 20, 2019, and Jan 23, 2020, were retrospectively enrolled. The cohort included 42 (52%) men and 39 (48%) women, and the mean age was 49·5 years (SD 11·0). The mean number of involved lung segments was 10·5 (SD 6·4) overall, 2·8 (3·3) in group 1, 11·1 (5·4) in group 2, 13·0 (5·7) in group 3, and 12·1 (5·9) in group 4. The predominant pattern of abnormality observed was bilateral (64 [79%] patients), peripheral (44 [54%]), ill-defined (66 [81%]), and ground-glass opacification (53 [65%]), mainly involving the right lower lobes (225 [27%] of 849 affected segments). In group 1 (n=15), the predominant pattern was unilateral (nine [60%]) and multifocal (eight [53%]) ground-glass opacities (14 [93%]). Lesions quickly evolved to bilateral (19 [90%]), diffuse (11 [52%]) ground-glass opacity predominance (17 [81%]) in group 2 (n=21). Thereafter, the prevalence of ground-glass opacities continued to decrease (17 [57%] of 30 patients in group 3, and five [33%] of 15 in group 4), and consolidation and mixed patterns became more frequent (12 [40%] in group 3, eight [53%] in group 4). Interpretation COVID-19 pneumonia manifests with chest CT imaging abnormalities, even in asymptomatic patients, with rapid evolution from focal unilateral to diffuse bilateral ground-glass opacities that progressed to or co-existed with consolidations within 1–3 weeks. Combining assessment of imaging features with clinical and laboratory findings could facilitate early diagnosis of COVID-19 pneumonia. Funding None.",2020,"Shi, Heshui; Han, Xiaoyu; Jiang, Nanchuan; Cao, Yukun; Alwalid, Osamah; Gu, Jin; Fan, Yanqing; Zheng, Chuansheng",The Lancet Infectious Diseases,3001118548,#1769,
,CZI,Initiation of a new infection control system for the COVID-19 outbreak,10.1016/S1473-3099(20)30110-9,,,,,,"Chen, Xuejiao; Tian, Junzhang; Li, Guanming; Li, Guowei",The Lancet Infectious Diseases,2914278034,#1195,
,CZI,The first Vietnamese case of COVID-19 acquired from China,10.1016/S1473-3099(20)30111-0,,,,,2020,"Van Cuong, Le; Giang, Hoang Thi Nam; Linh, Le Khac; Shah, Jaffer; Van Sy, Le; Hung, Trinh Huu; Reda, Abdullah; Truong, Luong Ngoc; Tien, Do Xuan; Huy, Nguyen Tien",The Lancet Infectious Diseases,2198156900,#1193,
,CZI,Viral load of SARS-CoV-2 in clinical samples,10.1016/S1473-3099(20)30113-4,,,,,2020,"Pan, Yang; Zhang, Daitao; Yang, Peng; Poon, Leo L. M.; Wang, Quanyi",The Lancet Infectious Diseases,2041451020,#1791,
,CZI,Asymptomatic cases in a family cluster with SARS-CoV-2 infection,10.1016/S1473-3099(20)30114-6,,,,,2020,"Pan, Xingfei; Chen, Dexiong; Xia, Yong; Wu, Xinwei; Li, Tangsheng; Ou, Xueting; Zhou, Liyang; Liu, Jing",The Lancet Infectious Diseases,3005688502,#1275,
,CZI,Open access epidemiological data from the COVID-19 outbreak,10.1016/S1473-3099(20)30119-5,,32087115,,,2020,"Xu, Bo; Kraemer, Moritz U. G.; Open, Covid-Data Curation Group",Lancet Infect Dis,3005879071,#1450,
,CZI,An interactive web-based dashboard to track COVID-19 in real time,10.1016/S1473-3099(20)30120-1,,,,,2020,"Dong, Ensheng; Du, Hongru; Gardner, Lauren",The Lancet Infectious Diseases,167054977,#1317,
,CZI,Correction to <em>Lancet Infect Dis</em> 2020; published online Feb 18. https://doi.org/10.1016/S1473-3099(20)30111-0,10.1016/S1473-3099(20)30128-6,,,,"Cuong LV, Giang HTN, Linh LC, et al. The first Vietnamese case of COVID-19 acquired from China. Lancet Infectious Diseases 2020; published online Feb 18. https://doi.org/10.1016/S1473-3099(20)30111-0—In this Letter, parts A and B in the figure were labelled the wrong way around. This correction has been made to the online version as of Feb 24, 2020, and will be made to the printed version.",2020,,The Lancet Infectious Diseases,2604173926,#2034,
,CZI,Can we contain the COVID-19 outbreak with the same measures as for SARS?,10.1016/S1473-3099(20)30129-8,,,,"The severe acute respiratory syndrome (SARS) outbreak in 2003 resulted in more than 8000 cases and 800 deaths. SARS was eventually contained by means of syndromic surveillance, prompt isolation of patients, strict enforcement of quarantine of all contacts, and in some areas top-down enforcement of community quarantine. By interrupting all human-to-human transmission, SARS was effectively eradicated. By contrast, by Feb 28, 2020, within a matter of 2 months since the beginning of the outbreak of coronavirus disease 2019 (COVID-19), more than 82?000 confirmed cases of COVID-19 have been reported with more than 2800 deaths. Although there are striking similarities between SARS and COVID-19, the differences in the virus characteristics will ultimately determine whether the same measures for SARS will also be successful for COVID-19. COVID-19 differs from SARS in terms of infectious period, transmissibility, clinical severity, and extent of community spread. Even if traditional public health measures are not able to fully contain the outbreak of COVID-19, they will still be effective in reducing peak incidence and global deaths. Exportations to other countries need not result in rapid large-scale outbreaks, if countries have the political will to rapidly implement countermeasures.",,"Wilder-Smith, Annelies; Chiew, Calvin J.; Lee, Vernon J.",The Lancet Infectious Diseases,3006642361,#4409,
,CZI,COVID-19: combining antiviral and anti-inflammatory treatments,10.1016/S1473-3099(20)30132-8,,,,"Both coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) are characterised by an overexuberant inflammatory response and, for SARS, viral load is not correlated with the worsening of symptoms. In our previous Correspondence to The Lancet, we described how BenevolentAI's proprietary artificial intelligence (AI)-derived knowledge graph, queried by a suite of algorithms, enabled identification of a target and a potential therapeutic against SARS coronavirus 2 (SARS-CoV-2; the causative organism in COVID-19). We identified a group of approved drugs that could inhibit clathrin-mediated endocytosis and thereby inhibit viral infection of cells (appendix). The drug targets are members of the numb-associated kinase (NAK) family—including AAK1 and GAK—the inhibition of which has been shown to reduce viral infection in vitro. Baricitinib was identified as a NAK inhibitor, with a particularly high affinity for AAK1, a pivotal regulator of clathrin-mediated endocytosis. We suggested that this drug could be of use in countering SARS-CoV-2 infections, subject to appropriate clinical testing.",,"Stebbing, Justin; Phelan, Anne; Griffin, Ivan; Tucker, Catherine; Oechsle, Olly; Smith, Dan; Richardson, Peter",The Lancet Infectious Diseases,2340158383,#2700,
,CZI,COVID-19 pneumonia: what has CT taught us?,10.1016/S1473-3099(20)30134-1,,,,,2020,"Lee, Elaine Y. P.; Ng, Ming-Yen; Khong, Pek-Lan",The Lancet Infectious Diseases,2009186097,#1818,
,CZI,Convalescent plasma as a potential therapy for COVID-19,10.1016/S1473-3099(20)30141-9,,,,,2020,"Chen, Long; Xiong, Jing; Bao, Lei; Shi, Yuan",The Lancet Infectious Diseases,2614362308,#2668,
,CZI,"A family cluster of SARS-CoV-2 infection involving 11 patients in Nanjing, China",10.1016/S1473-3099(20)30147-X,,,,,2020,"Huang, Rui; Xia, Juan; Chen, Yuxin; Shan, Chun; Wu, Chao",The Lancet Infectious Diseases,3006355661,#2836,
,CZI,Taking the right measures to control COVID-19,10.1016/S1473-3099(20)30152-3,,,,"First, although COVID-19 is spread by the airborne route, air disinfection of cities and communities is not known to be effective for disease control and needs to be stopped. The widespread practice of spraying disinfectant and alcohol in the sky, on roads, vehicles, and personnel has no value; moreover, large quantities of alcohol and disinfectant are potentially harmful to humans and should be avoided.3 , 4 Second, in the use of personal protective equipment, we should try to distinguish different risk factors, adopt different epidemic prevention measures, and reduce the waste of personal protective equipment, as these resources are already in short supply. Although surgical masks are in widespread use by the general population, there is no evidence that these masks prevent the acquisition of COVID-19, although they might slightly reduce the spread from an infected patient. High-filtration masks such as N95 masks and protective clothing (goggles and gowns) should be used in hospitals where health-care workers are in direct contact with infected patients.5 Third, the practice of blocking traffic and lockdown of villages is of no value for the prevention and control of COVID-19. Since the outbreak of COVID-19, some countries have suspended flights to and from China, and prevented Chinese people from travelling to their countries; both of these actions violate WHO International Health Regulations.6 Similarly, in community prevention and control of the disease, the measures taken by individual villages and communities to seal off roads are of no value.7 Such measures could result in civil unrest and reduce compliance with infection prevention and control advice. Fourth, public health education must be based on scientific evidence to reduce the anxiety and distress caused by misinformation. In particular, epidemiological findings need to be reported in a timely and objective manner so that they can be accurately assessed and interpreted. The risk of transmission with brief contact (less than 15 min face-to-face contact) or infection onset after 14 days of exposure to a known infected person (the estimated maximum incubation period) is low and should not be over-exaggerated. Misinformation spreads panic among the general population and is not conducive to implementation of epidemic control measures.8 Fifth, WHO has made it clear that there are currently no known effective treatments for COVID-19 and does not recommend the use of antiviral drugs, antibiotics, glucocorticoids, or traditional Chinese medicine. Despite this, there have been reports of the use of oseltamivir, lopinavir/ritonavir, prednisone, antibiotics, and traditional Chinese medicine for the treatment of patients with COVID-19.9 Care should be taken to not give patients drugs of unknown efficacy, which might be detrimental to critically ill patients with COVID-19; clinical trials are urgently required in this context.10 Likewise, the development of a vaccine is an urgent public health priority.",,"Xiao, Yonghong; Torok, Mili Estee",The Lancet Infectious Diseases,3006007867,#4397,
,CZI,Guidelines for pregnant women with suspected SARS-CoV-2 infection,10.1016/S1473-3099(20)30157-2,,,,"Coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) can cause severe adverse pregnancy outcomes, such as miscarriage, premature delivery, intrauterine growth restriction, and maternal death.1 , 2 Vertical transmission of the virus responsible for 2019 novel coronavirus disease (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has not yet been detected, whereas perinatal transmission has been suspected in one case.3 Consequences of infection with SARS-CoV-2 for pregnancies are uncertain, with no evidence so far of severe outcomes for mothers and infants; however, the possibility should be considered.4 The recent experience with Zika virus suggests that when a new pathogen emerges, the health-care community should be prepared for the worst-case scenario.5 Therefore, recommendations for management of pregnant women at risk of SARS-CoV-2 infection are urgently needed. To this end, we propose a detailed management algorithm for health-care providers (appendix).",,"Favre, Guillaume; Pomar, Léo; Qi, Xiaolong; Nielsen-Saines, Karin; Musso, Didier; Baud, David",The Lancet Infectious Diseases,1940662020,#3484,
,CZI,Covert COVID-19 and false-positive dengue serology in Singapore,10.1016/S1473-3099(20)30158-4,,,,"Dengue and coronavirus disease 2019 (COVID-19) are difficult to distinguish because they have shared clinical and laboratory features.1 , 2 We describe two patients in Singapore with false-positive results from rapid serological testing for dengue, who were later confirmed to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative virus of COVID-19. The first case is a 57-year-old man with no relevant past medical, travel, or contact history, who presented to a regional hospital on Feb 9, 2020, with 3 days of fever and cough. He had thrombocytopenia (platelet count 140 × 109/mL) and a normal chest radiograph. He was discharged after a negative rapid test for dengue NS1, IgM, and IgG (SD Bioline Dengue Duo Kit; Abbott, South Korea). He returned to a public primary health-care clinic with persistent fever, worsening thrombocytopenia (89 × 109/mL), and new onset lymphopenia (0·43 × 109/mL). A repeat dengue rapid test was positive for dengue IgM and IgG (Dengue Combo; Wells Bio, South Korea). He was referred to hospital for dengue with worsening cough and dyspnoea. A chest radiograph led to testing for SARS-CoV-2 by RT-PCR (in-house laboratory-developed test detecting the N and ORF1ab genes) from a nasopharyngeal swab, which returned positive. The original seropositive sample and additional urine and blood samples tested negative for dengue, chikungunya, and Zika viruses by RT-PCR,3 , 4 , 5 and a repeat dengue rapid test (SD Bioline) was also negative. Thus, the initial dengue seroconversion result was deemed a false positive.",,"Yan, Gabriel; Lee, Chun Kiat; Lam, Lawrence T. M.; Yan, Benedict; Chua, Ying Xian; Lim, Anita Y. N.; Phang, Kee Fong; Kew, Guan Sen; Teng, Hazel; Ngai, Chin Hong; Lin, Li; Foo, Rui Min; Pada, Surinder; Ng, Lee Ching; Tambyah, Paul Anantharajah",The Lancet Infectious Diseases,2810796836,#4251,
,CZI,Outbreak investigation for COVID-19 in northern Vietnam,10.1016/S1473-3099(20)30159-6,,,,"Two Vietnamese adults returned to their home province of Vinh Phuc in northern Vietnam on Jan 17, 2020, from Wuhan, China, where they had been living since Nov 15, 2019, for a business trip. They presented with mild respiratory symptoms to their local health facilities at 4 days and 8 days, respectively, after arrival in Vinh Phuc. Both individuals were initially placed into respiratory isolation in hospital. Case 1 tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative organism of coronavirus disease 2019 (COVID-19), on Jan 30, 2020, and remained in isolation until recovery. Case 2 was discharged from isolation in hospital after having one negative test result on Jan 28 (11 days after returning from Wuhan). Following discharge, the patient attended a family social function. 2 days later, she was readmitted after a second nasal swab for SARS-CoV-2 taken during her time in hospital was reported as positive. Screening of 79 individuals who had been in contact with these two patients (namely, family members in the same household and anyone who had been within 2 m of them) was initiated on Jan 31. Six individuals from the same work team, who had also travelled from Wuhan on Jan 17, were isolated, and four of them tested positive for SARS-CoV-2 (cases 3, 4, and 8 in Vinh Phuc, and one case from another province). Five secondary cases were diagnosed within the social network of case 2. These included three household members (cases 6, 7, and 11) and two people who had attended the social function (cases 5 and 9; appendix p 1). Four of these individuals reported mild respiratory symptoms; the remaining patient was asymptomatic (case 7) at the time of diagnosis.",,"Thanh, Hai Nguyen; Van, Truong Nguyen; Thu, Huong Ngo Thi; Van, Binh Nghiem; Thanh, Binh Doan; Thu, Ha Phung Thi; Kieu, Anh Nguyen Thi; Viet, Nhung Nguyen; Marks, Guy B.; Fox, Greg J.; Nguyen, Thu-Anh",The Lancet Infectious Diseases,2904779985,#4012,
,CZI,"Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial",10.1016/S2213-2600(19)30417-5,,,,"BackgroundThere is no proven specific pharmacological treatment for patients with the acute respiratory distress syndrome (ARDS). The efficacy of corticosteroids in ARDS remains controversial. We aimed to assess the effects of dexamethasone in ARDS, which might change pulmonary and systemic inflammation and result in a decrease in duration of mechanical ventilation and mortality.",,"Villar, Jesús; Ferrando, Carlos; Martínez, Domingo; Ambrós, Alfonso; Muñoz, Tomás; Soler, Juan A.; Aguilar, Gerardo; Alba, Francisco; González-Higueras, Elena; Conesa, Luís A.; Martín-Rodríguez, Carmen; Díaz-Domínguez, Francisco J.; Serna-Grande, Pablo; Rivas, Rosana; Ferreres, José; Belda, Javier; Capilla, Lucía; Tallet, Alec; Añón, José M.; Fernández, Rosa L.; González-Martín, Jesús M.; Álvarez, Julián; Asensio, María J.; Blanco, Jesús; Blasco, Marisa; Cachafeiro, Lucia; del Campo, Rafael; Carbonell, José A.; Carbonell, Nieves; Cariñena, Agustín; Carriedo, Demetrio; Chico, Mario; Corpas, Ruth; Cuervo, Javier; Domínguez-Antelo, Cristina; Fernández, Lorena; Gamboa, Eneritz; González-Luengo, Raúl I.; Ortiz Díaz-Miguel, Ramón; Pérez-González, Raquel; Prieto, Ana M.; Prieto, Isidro; Rojas-Viguera, Leticia; Romera, Miguel A.; Sánchez-Ballesteros, Jesús; Segura, José M.; Serrano, Ainhoa; Solano, Rosario; Soro, Marina",The Lancet Respiratory Medicine,3004626187,#510,
,CZI,Coronavirus in China,10.1016/S2213-2600(20)30056-4,,,,"On Dec 31, 2019, China alerted WHO to several cases of pneumonia associated with an unknown virus. The cases were concentrated in Wuhan City, in Hubei Province in central China, home to 11 million people. By Jan 7, 2020, there was confirmation that a new type of coronavirus had emerged. It was temporarily named 2019-nCoV. It is the seventh identified coronavirus that can cause diseases of the respiratory tract in humans. On Jan 9, there was the first reported death from 2019-nCoV—a 61-year-old man who had visited the now-closed Huanan Seafood Wholesale Market, where the virus is thought to have originated. As of Jan 30, 2020, 7736 confirmed cases of 2019-nCoV had been reported in China, with a further 12?167 suspected cases. There had been 1370 severe cases, and 170 deaths. A few dozen additional cases had been detected in 18 countries around the world, of which only seven cases had no history of travel in China.",,"Burki, Talha Khan",The Lancet Respiratory Medicine,3004220385,#201,
,CZI,Coronavirus epidemic: preparing for extracorporeal organ support in intensive care,10.1016/S2213-2600(20)30060-6,,,,,2020,"Ronco, Claudio; Navalesi, Paolo; Vincent, Jean Louis",The Lancet Respiratory Medicine,3004784537,#379,
,CZI,Australian Government releases face masks to protect against coronavirus,10.1016/S2213-2600(20)30064-3,,,,,2020,"Kirby, Tony",The Lancet Respiratory Medicine,3004752580,#512,
,CZI,Protecting health-care workers from subclinical coronavirus infection,10.1016/S2213-2600(20)30066-7,,,,,2020,"Chang, De; Xu, Huiwen; Rebaza, Andre; Sharma, Lokesh; Dela Cruz, Charles S.",The Lancet Respiratory Medicine,3005798348,#833,
,CZI,Toning down the 2019-nCoV media hype—and restoring hope,10.1016/S2213-2600(20)30070-9,,,,,2020,"Ippolito, Giuseppe; Hui, David S.; Ntoumi, Francine; Maeurer, Markus; Zumla, Alimuddin",The Lancet Respiratory Medicine,,#768,
,CZI,Therapeutic and triage strategies for 2019 novel coronavirus disease in fever clinics,10.1016/S2213-2600(20)30071-0,,,,,2020,"Zhang, Jinnong; Zhou, Luqian; Yang, Yuqiong; Peng, Wei; Wang, Wenjing; Chen, Xuelin",The Lancet Respiratory Medicine,3005678464,#832,
,CZI,Pathological findings of COVID-19 associated with acute respiratory distress syndrome,10.1016/S2213-2600(20)30076-X,,,,,2020,"Xu, Zhe; Shi, Lei; Wang, Yijin; Zhang, Jiyuan; Huang, Lei; Zhang, Chao; Liu, Shuhong; Zhao, Peng; Liu, Hongxia; Zhu, Li; Tai, Yanhong; Bai, Changqing; Gao, Tingting; Song, Jinwen; Xia, Peng; Dong, Jinghui; Zhao, Jingmin; Wang, Fu-Sheng",The Lancet Respiratory Medicine,2835497422,#1187,
,CZI,"Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study",10.1016/S2213-2600(20)30079-5,,,,"Summary Background An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding None.",2020,"Yang, Xiaobo; Yu, Yuan; Xu, Jiqian; Shu, Huaqing; Xia, Jia'an; Liu, Hong; Wu, Yongran; Zhang, Lu; Yu, Zhui; Fang, Minghao; Yu, Ting; Wang, Yaxin; Pan, Shangwen; Zou, Xiaojing; Yuan, Shiying; Shang, You",The Lancet Respiratory Medicine,2109520345,#1733,
,CZI,Pandemic: examining readiness for infectious disease outbreaks,10.1016/S2213-2600(20)30082-5,,,,,2020,"Burki, Talha Khan",The Lancet Respiratory Medicine,1982319340,#1411,
,CZI,Staff safety during emergency airway management for COVID-19 in Hong Kong,10.1016/S2213-2600(20)30084-9,,,,,2020,"Cheung, Jonathan Chun-Hei; Ho, Lap Tin; Cheng, Justin Vincent; Cham, Esther Yin Kwan; Lam, Koon Ngai",The Lancet Respiratory Medicine,2774197594,#1857,
,CZI,Correction to <em>Lancet Respir Med</em> 2020; published online Feb 17. https://doi.org/10.1016/S2213-2600(20)30076-X,10.1016/S2213-2600(20)30085-0,,,,"Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020; published online Feb 17. https://doi.org/10.1016/S2213-2600(20)30076-X—In this Case Report “by obtaining biopsy samples at autopsy” has been replace with “by postmortem biopsies” in paragraph 1, “microvascular” has been replaced with “microvesicular” in two incidences in paragraph 5, and “(B) Frequency of Th17 (CD4+ CCR6+CCR4+) subset” has been changed to “(B) Frequency of Th17 (CD4+ CCR6+) subset” on page 3 of the appendix. These corrections have been made to the online version as of Feb 25, 2020, and will be made to the printed version.",,,The Lancet Respiratory Medicine,2913752377,#2035,
,CZI,Respiratory support for patients with COVID-19 infection,10.1016/S2213-2600(20)30110-7,,,,"As of Feb 27, 2020, coronavirus disease 2019 (COVID-19) has affected 47 countries and territories around the world.1 Xiaobo Yang and colleagues2 described 52 of 710 patients with confirmed COVID-19 admitted to an intensive care unit (ICU) in Wuhan, China. 29 (56%) of 52 patients were given non-invasive ventilation at ICU admission, of whom 22 (76%) required further orotracheal intubation and invasive mechanical ventilation. The ICU mortality rate among those who required non-invasive ventilation was 23 (79%) of 29 and among those who required invasive mechanical ventilation was 19 (86%) of 22.2 Jonathan Chun-Hei Cheung and colleagues3 do not recommend use of a high-flow nasal cannula or non-invasive ventilation until the patient has viral clearance. Supporting the recommendation of the authors, I would like to add some points in relation to the use of high-flow nasal oxygen therapy and non-invasive ventilation in patients with COVID-19 infection: First, although exhaled air dispersion during high-flow nasal oxygen therapy and non-invasive ventilation via different interfaces is restricted, provided that there is a good mask interface fitting,4 not all hospitals around the world have access to such interfaces or enough personal-protective equipment of sufficiently high quality (ie, considered fit-tested particulate respirators, N95 or equivalent, or higher level of protection) for aerosol-generating procedures, and several hospitals do not have a negative pressure isolation room. Of 1688 health-care workers who have become infected with COVID-19, five (0·3%) have died;5 a sign of the vastly difficult working conditions for health-care workers.",,"Ñamendys-Silva, Silvio A.",The Lancet Respiratory Medicine,2379191983,#4491,
,CZI,Correction to Lancet Glob Health 2020; published online Feb 28. https://doi.org/10.1016/S2214-109X(20)30074-7,10.1016/S2214-109X(20)30083-8,,,,,2020,,The Lancet Global Health,2322586088,#4643,
,CZI,Timely mental health care for the 2019 novel coronavirus outbreak is urgently needed,10.1016/S2215-0366(20)30046-8,,,,"The 2019 novel coronavirus (2019-nCoV) pneumonia, believed to have originated in a wet market in Wuhan, Hubei province, China at the end of 2019, has gained intense attention nationwide and globally. To lower the risk of further disease transmission, the authority in Wuhan suspended public transport indefinitely from Jan 23, 2020; similar measures were adopted soon in many other cities in China. As of Jan 25, 2020, 30 Chinese provinces, municipalities, and autonomous regions covering over 1·3 billion people have initiated first-level responses to major public health emergencies. A range of measures has been urgently adopted,1,2 such as early identification and isolation of suspected and diagnosed cases, contact tracing and monitoring, collection of clinical data and biological samples from patients, dissemination of regional and national diagnostic criteria and expert treatment consensus, establishment of isolation units and hospitals, and prompt provision of medical supplies and external expert teams to Hubei province. The emergence of the 2019-nCoV pneumonia has parallels with the 2003 outbreak of severe acute respiratory syndrome (SARS), which was caused by another coronavirus that killed 349 of 5327 patients with confirmed infection in China.3 Although the diseases have different clinical presentations, the infectious cause, epidemiological features, fast transmission pattern, and insufficient preparedness of health authorities to address the outbreaks are similar. So far, mental health care for the patients and health professionals directly affected by the 2019-nCoV epidemic has been under-addressed, although the National Health Commission of China released the notification of basic principles for emergency psychological crisis interventions for the 2019-nCoV pneumonia on Jan 26, 2020. This notification contained a reference to mental health problems and interventions that occurred during the 2003 SARS outbreak, and mentioned that mental health care should be provided for patients with 2019-nCoV pneumonitis, close contacts, suspected cases who are isolated at home, patients in fever clinics, families and friends of affected people, health professionals caring for infected patients, and the public who are in need. To date, epidemiological data on the mental health problems and psychiatric morbidity of those suspected or diagnosed with the 2019-nCoV and their treating health professionals have not been available; therefore how best to respond to challenges during the outbreak is unknown. The observations of mental health consequences and measures taken during the 2003 SARS outbreak could help inform health authorities and the public to provide mental health interventions to those who are in need.",,"Xiang, Yu-Tao; Yang, Yuan; Li, Wen; Zhang, Ling; Zhang, Qinge; Cheung, Teris; Ng, Chee H.",The Lancet Psychiatry,3004804052,#207,
,CZI,"The mental health of medical workers in Wuhan, China dealing with the 2019 novel coronavirus",10.1016/S2215-0366(20)30047-X,,,,"The severe situation is causing mental health problems such as stress, anxiety, depressive symptoms, insomnia, denial, anger, and fear. These mental health problems not only affect the medical workers' attention, understanding, and decision making ability, which might hinder the fight against 2019-nCoV, but could also have a lasting effect on their overall wellbeing. Protecting the mental health of these medical workers is thus important for control of the epidemic and their own long-term health. The local government of Wuhan has implemented policies to address these mental health problems. Medical staff infected with 2019-nCoV while at work will be identified as having work-related injuries.As of Jan 25, 2020, 1230 medical workers have been sent from other provinces to Wuhan to care for patients who are infected and those with suspected infection, strengthen logistics support, and help reduce the pressure on health-care personnel.Most general hospitals in Wuhan have established a shift system to allow front-line medical workers to rest and to take turns in high-pressured roles. Online platforms with medical advice have been provided to share information on how to decrease the risk of transmission between the patients in medical settings, which aims to eventually reduce the pressure on medical workers.",,"Kang, Lijun; Li, Yi; Hu, Shaohua; Chen, Min; Yang, Can; Yang, Bing Xiang; Wang, Ying; Hu, Jianbo; Lai, Jianbo; Ma, Xiancang; Chen, Jun; Guan, Lili; Wang, Gaohua; Ma, Hong; Liu, Zhongchun",The Lancet Psychiatry,3005207746,#317,
,CZI,Psychological interventions for people affected by the COVID-19 epidemic,10.1016/S2215-0366(20)30073-0,,,,,2020,"Duan, Li; Zhu, Gang",The Lancet Psychiatry,2556905174,#1316,
,CZI,The neglected health of international migrant workers in the COVID-19 epidemic,10.1016/S2215-0366(20)30076-6,,,,,2020,"Liem, Andrian; Wang, Cheng; Wariyanti, Yosa; Latkin, Carl A.; Hall, Brian J.",The Lancet Psychiatry,3006304371,#1289,
,CZI,Online mental health services in China during the COVID-19 outbreak,10.1016/S2215-0366(20)30077-8,,,,,,"Liu, Shuai; Yang, Lulu; Zhang, Chenxi; Xiang, Yu-Tao; Liu, Zhongchun; Hu, Shaohua; Zhang, Bin",The Lancet Psychiatry,2020421786,#1189,
,CZI,Mental health care for medical staff in China during the COVID-19 outbreak,10.1016/S2215-0366(20)30078-X,,,,,,"Chen, Qiongni; Liang, Mining; Li, Yamin; Guo, Jincai; Fei, Dongxue; Wang, Ling; He, Li; Sheng, Caihua; Cai, Yiwen; Li, Xiaojuan; Wang, Jianjian; Zhang, Zhanzhou",The Lancet Psychiatry,2896665283,#1191,
,CZI,Mental health services for older adults in China during the COVID-19 outbreak,10.1016/S2215-0366(20)30079-1,,,,,2020,"Yang, Yuan; Li, Wen; Zhang, Qinge; Zhang, Ling; Cheung, Teris; Xiang, Yu-Tao",The Lancet Psychiatry,2129112369,#1188,
,CZI,A contingency plan for the management of the 2019 novel coronavirus outbreak in neonatal intensive care units,10.1016/S2352-4642(20)30040-7,,,,,,"Wang, Jianhui; Qi, Hongbo; Bao, Lei; Li, Fang; Shi, Yuan",The Lancet Child & Adolescent Health,3004657851,#517,
,CZI,Managing neonates with respiratory failure due to SARS-CoV-2 – Authors' reply,10.1016/S2352-4642(20)30072-9,,,,"Since December, 2019, a pneumonia of unknown cause, which has clinical manifestations similar to severe acute respiratory syndrome,1,2 originated in Wuhan, China, and has rapidly spread across China and to at least 23 countries. By Feb 5, 2020, the number of laboratory-confirmed cases had exceeded 20 000, with more than 400 deaths. About 100 children were affected, with the youngest being 30 h after birth. A novel virus named 2019 novel coronavirus (2019-nCoV) was considered to be the causative agent of this pneumonia. Neonates are thought to be susceptible to the virus because their immune system is not well developed, which is of great concern to neonatal medical service providers. Paediatricians and neonatologists belonging to the National Clinical Research Center for Child Health and Disorders and Pediatric Committee of Medical Association of Chinese People’s Liberation Army have contributed to the control efforts in China. We aim to elicit a contingency plan for the 2019-nCoV outbreak in neonatal intensive care units (NICUs), mainly focused on diagnostic and discharge criteria, treatment, prevention, and control strategies",2020,"Wang, Jianhui; Shi, Yuan",The Lancet Child & Adolescent Health,,#5270,
,CZI,Managing neonates with respiratory failure due to SARS-CoV-2,10.1016/S2352-4642(20)30073-0,,,,"In their Comment in The Lancet Child & Adolescent Health, Jianhui Wang and colleagues1 suggested a plan to handle neonates with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and outbreaks in neonatal intensive care units (NICUs). This is a timely reflection, given the public health problem represented by this infection and the need to anticipate any critical care issue, irrespective of patients' ages. However, the plan is incomplete or unsuitable in many points. We do not know anything about neonatal SARS-CoV-2 infections, and we must reasonably follow data from adult critical care. First, testing all NICU-admitted neonates for SARS-CoV-2 represents a wrongful use of resources. Neonatal respiratory failure can result from a wide range of causes, and testing everybody when other causes are reasonably suspected will divert laboratory resources from adult critical care. Tests should be done for infants from families infected by SARS-CoV-2 or exposed to other infected people, irrespective of their symptoms.",,"De Luca, Daniele",The Lancet Child & Adolescent Health,2002765492,#5421,
,CZI,Enteric involvement of coronaviruses: is faecal–oral transmission of SARS-CoV-2 possible?,10.1016/S2468-1253(20)30048-0,,,,,2020,"Yeo, Charleen; Kaushal, Sanghvi; Yeo, Danson",The Lancet Gastroenterology & Hepatology,,#1260,
,CZI,Liver injury in COVID-19: management and challenges,10.1016/S2468-1253(20)30057-1,,,,"SARS-CoV-2 shares 82% genome sequence similarity to SARS-CoV and 50% genome sequence homology to Middle East respiratory syndrome coronavirus (MERS-CoV)—all three coronaviruses are known to cause severe respiratory symptoms. Liver impairment has been reported in up to 60% of patients with SARS3 and has also been reported in patients infected with MERS-CoV.4 At least seven relatively large-scale case studies have reported the clinical features of patients with COVID-19.1 , 5 , 6 , 7 , 8 , 9 , 10 In this Comment, we assess how the liver is affected using the available case studies and data from The Fifth Medical Center of PLS General Hospital, Beijing, China. These data indicate that 2–11% of patients with COVID-19 had liver comorbidities and 14–53% cases reported abnormal levels of alanine aminotransferase and aspartate aminotransferase (AST) during disease progression (table). Patients with severe COVID-19 seem to have higher rates of liver dysfunction. In a study in The Lancet by Huang and colleagues,5 elevation of AST was observed in eight (62%) of 13 patients in the intensive care unit (ICU) compared with seven (25%) of 28 patients who did not require care in the ICU. Moreover, in a large cohort including 1099 patients from 552 hospitals in 31 provinces or provincial municipalities, more severe patients with disease had abnormal liver aminotransferase levels than did non-severe patients with disease.1 Furthermore, in another study,8 patients who had a diagnosis of COVID-19 confirmed by CT scan while in the subclinical phase (ie, before symptom onset) had significantly lower incidence of AST abnormality than did patients diagnosed after the onset of symptoms. Therefore, liver injury is more prevalent in severe cases than in mild cases of COVID-19.",,"Zhang, Chao; Shi, Lei; Wang, Fu-Sheng",The Lancet Gastroenterology & Hepatology,2398802113,#4278,
,CZI,Novel Coronavirus and Hospital Infection Prevention: Preparing for the Impromptu Speech,10.1017/ice.2020.55,,32122422,,,2020,"Bearman, Gonzalo; Pryor, Rachel; Albert, Heather; Brath, Lisa; Britton, Amy; Cooper, Kaila; Doll, Michelle; Godbout, Emily J.; Hemphill, Robin; Stevens, Michael P.",Infect Control Hosp Epidemiol,1736130314,#3457,
,CZI,Escalating infection control response to the rapidly evolving epidemiology of the Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 in Hong Kong,10.1017/ice.2020.58,,,,"Background:To describe the infection control preparedness for Coronavirus Disease (COVID-19) due to SARS-CoV-2 [previously known as 2019-novel coronavirus] in the first 42 days after announcement of a cluster of pneumonia in China, on 31 December 2019 (day 1) in Hong Kong.Methods:A bundle approach of active and enhanced laboratory surveillance, early airborne infection isolation, rapid molecular diagnostic testing, and contact tracing for healthcare workers (HCWs) with unprotected exposure in the hospitals was implemented. Epidemiological characteristics of confirmed cases, environmental and air samples were collected and analyzed.Results:From day 1 to day 42, forty-two (3.3%) of 1275 patients fulfilling active (n=29) and enhanced laboratory surveillance (n=13) confirmed to have SARS-CoV-2 infection. The number of locally acquired case significantly increased from 1 (7.7%) of 13 [day 22 to day 32] to 27 (93.1%) of 29 confirmed case [day 33 to day 42] (p&lt;0.001). Twenty-eight patients (66.6%) came from 8 family clusters. Eleven (2.7%) of 413 HCWs caring these confirmed cases were found to have unprotected exposure requiring quarantine for 14 days. None of them was infected and nosocomial transmission of SARS-CoV-2 was not observed. Environmental surveillance performed in a patient with viral load of 3.3x106 copies/ml (pooled nasopharyngeal/ throat swab) and 5.9x106 copies/ml (saliva) respectively. SARS-CoV-2 revealed in 1 (7.7%) of 13 environmental samples, but not in 8 air samples collected at a distance of 10 cm from patient's chin with or without wearing a surgical mask.Conclusion:Appropriate hospital infection control measures could prevent nosocomial transmission of SARS-CoV-2.",,"Cheng, Vincent C. C.; Wong, Shuk-Ching; Chen, Jonathan H. K.; Yip, Cyril C. Y.; Chuang, Vivien W. M.; Tsang, Owen T. Y.; Sridhar, Siddharth; Chan, Jasper F. W.; Ho, Pak-Leung; Yuen, Kwok-Yung",Infection Control & Hospital Epidemiology,2040330380,#4656,
,CZI,Protecting Chinese Healthcare Workers While Combating the 2019 Novel Coronavirus,10.1017/ice.2020.60,,,,"Hospital-associated transmission is an important route of spreading the 2019 novel coronavirus (2019-nCoV) infection and pneumonia (Corona Virus Disease 2019, COVID-19) [1]. Healthcare workers (HCWs) are at high risk while combating COVID-19 at the very frontline, and nosocomial outbreaks among HCWs are not unusual in similar settings; the 2003 severe acute respiratory syndrome (SARS) outbreak led to over 966 HCW infections with 1.4% deaths in mainland China [2]. As of 11 February 2020, 3019 HCWs might have been infected with 2019-nCov in China, 1716 HCW cases were confirmed by nucleic acid testing[3], and at least 6 HCWs died, including the famous whistleblower Dr Li Wenliang. In view of this severe situation, we are recommending urgent interventions to help to protect HCWs.",,"Zhou, Pengcheng; Huang, Zebing; Xiao, Yinzong; Huang, Xun; Fan, Xue-Gong",Infection Control & Hospital Epidemiology,3004450134,#4651,
,CZI,The novel coronavirus (COVID-19) infection in Hangzhou: An experience to share,10.1017/ice.2020.62,,,,"Current situation in Hangzhou Hangzhou, the capital of Zhejiang province in China, was confronted with the pandemic of a novel coronavirus (COVID-19) that originated in Wuhan, Hubei province1 . According to the Health Commission of Zhejiang Province2 , six cases was first reported on January 19, 2020, and the cumulative cases reached 169 as of February 20, 2020. The situation in Hangzhou was once rather severe as it was once the top ranking city with respect to number of confirmed cases in Zhejiang province at the beginning of the epidemic. Since Hangzhou government took rigorous measures to contain the epidemic, positive trends have been seen. The daily number of newly confirmed cases has sharply decreased within the last week and there was only one confirmed case from February 17 to 20. Similarly, another point to be emphasized was that Hangzhou reported no deaths in its administrative region. We used a regression of log-incidence over time model3 ,which could provide a fitted trajectory for the actual daily incidence to verify the control effect. As show in Fig.1, the optimal splitting point, which was defined as the peak in number of daily new cases simulated by the model, occurred on January 25. That date was just about a week after launching the highest level of emergency public health alert and response in Hangzhou, which indicates that the prevention and control measures may be effective",,"Diao, MengYuan; Zhang, Sheng; Chen, Dechang; Hu, Wei",Infection Control & Hospital Epidemiology,3005847234,#4654,
,CZI,"The time-varying serial interval of the coronavirus disease (COVID-19) and its gender-specific difference: A data-driven analysis using public surveillance data in Hong Kong and Shenzhen, China from January 10 to February 15, 2020",10.1017/ice.2020.64,,,,"To the Editor. An outbreak of coronavirus disease (COVID-19), started in Wuhan, China in the end of 2019 [1], has now reached 40 countries and poses huge threat to global public health and economic [2]. Given the risk of human-to-human transmission, the serial interval (SI), which refers to the time interval from symptom onset of a primary case (i.e., infector) to that of a secondary case (i.e., infectee) [3], is the other essential quantity besides the basic reproduction number to drive the spreading speed. We examine the publicly available materials and collect the records of COVID-19 transmission events in two neighboring large cities, Hong Kong [4] and Shenzhen [5], in south China from January 10 to February 15, 2020 and extract the SI data. We identify 48 transmission events including 21 in Hong Kong and 27 in Shenzhen, among which 40 events contain the gender information of the primary cases. The last onset date of the primary cases among all collected transmission events is February 2, 2020.",,"Zhao, Shi; Cao, Peihua; Chong, Marc K. C.; Gao, Daozhou; Lou, Yijun; Ran, Jinjun; Wang, Kai; Wang, Weiming; Yang, Lin; He, Daihai; Wang, Maggie H.",Infection Control & Hospital Epidemiology,3006643024,#5426,
,CZI,Structure-based stabilization of non-native protein-protein interactions of coronavirus nucleocapsid proteins in antiviral drug design,10.1021/acs.jmedchem.9b01913,,,,"Structure-based stabilization of protein-protein interactions (PPIs) is a promising strategy for drug discovery. However, this approach has mainly focused on the stabilization of native PPIs and non-native PPIs have received little consideration. Here, we identified a non-native interaction interface on the 3D dimeric structure of the N-terminal domain of the MERS-CoV nucleocapsid protein (MERS-CoV N-NTD). The interface formed a conserved hydrophobic cavity suitable for targeted drug screening. By considering the hydrophobic complementarity during the virtual screening step, we identified 5-benzyloxygramine as a new N protein PPI orthosteric stabilizer that possesses both antiviral and N-NTD protein-stabilizing activity. X-ray crystallography and small-angle X-ray scattering showed that 5-benzyloxygramine stabilizes the N-NTD dimers through simultaneous hydrophobic interactions to both partners, resulting in abnormal N protein oligomerization that was further confirmed in the cell. This unique approach based on the identification and stabilization of non-native PPIs of N protein could be applied towards drug discovery against CoV diseases.",2020,"Lin, Shan-Meng; Lin, Shih-Chao; Hsu, Jia-Ning; Chang, Chung-ke; Chien, Ching-Ming; Wang, Yong-Sheng; Wu, Hung-Yi; Jeng, U. Ser; Kehn-Hall, Kylene; Hou, Ming-hon",Journal of Medicinal Chemistry,2035437208,#2598,
,CZI,Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential,10.1021/acsinfecdis.0c00052,,32125140,,"The recent outbreak of coronavirus disease 2019 (COVID-19) highlights an urgent need for therapeutics. Through a series of drug repurposing screening campaigns, niclosamide, an FDA-approved anthelminthic drug, was found to be effective against various viral infections with nanomolar to micromolar potency such as SARS-CoV, MERS-CoV, ZIKV, HCV and human adenovirus, indicating its potential as an antiviral agent. In this brief article, we summarize the broad antiviral activities of niclosamide and highlight its potential clinical use for treatment of COVID-19.",2020,"Xu, Jimin; Shi, Pei-Yong; Li, Hongmin; Zhou, Jia",ACS Infect Dis,2021189636,#3265,
,CZI,Pharma mobilizes to combat the coronavirus,10.1021/cen-09805-buscon4,,,,"The World Health Organization has declared the fast-moving coronavirus outbreak in China a “public health emergency of international concern,” a measure that can spur coordinated global efforts to combat it. With infections steadily rising, major drug companies are mobilizing to develop diagnostics, vaccines, and possible treatments for the virus, 2019-nCoV. According to WHO, as of Jan. 30 more than 7,800 people worldwide are confirmed to have been infected by the virus, and another 12,000-plus cases are suspected. Almost all of the cases are in China, where 170 people have died. Although smaller biotech firms were among the first to publicly respond to the outbreak, big pharma firms say they have been quietly working on tests and treatments for several weeks. Roche has sent the first commercial diagnostic to China, and Johnson & Johnson says it is using the same technologies deployed for the rapid development of an Ebola vaccine to(..)",2020,,C&EN Global Enterprise,2095772697,#807,
,CZI,China’s chemical industry shadowed by the coronavirus,10.1021/cen-09806-buscon1,,,,"With its escalating infections, city shutdowns, and nationwide transportation halts, the epidemic of the novel coronavirus is starting to strain China’s chemical industry. But experts see the impact as manageable and—they hope—short lived. By the afternoon of Feb. 6, more than 28,000 people in China were confirmed infected with the virus, almost 20,000 of them in the central Chinese province of Hubei. The death toll in China was 564, compared with 349 deaths in all of China from the severe acute respiratory syndrome (SARS) virus in 2003. The government shut down travel in and out of all cities in Hubei and extended the Lunar New Year holiday until Feb. 9 or 10 for most factories nationwide. Even if the epidemic is controlled in the next few months, frozen consumption, reduced factory output, and disturbed supply chains will cut 0.1 to 0.2 percentage points from global economic growth in 2020, according",2020,,C&EN Global Enterprise,,#1002,
,CZI,Coronavirus puts drug chemical industry on alert,10.1021/cen-09806-buscon2,,,,"Major drug companies have issued statements in recent days assuring the public that their inventories are adequate in the face of supply chain threats stemming from the novel coronavirus. Suppliers of active pharmaceutical ingredients (APIs) are also assuring customers that they are prepared for temporary interruption in the supply of key ingredients from firms in China, where the outbreak originated. API makers in Europe and the US warn, however, that supply disruptions could result from a protracted delay in restarting production at plants closed in recent weeks by the Chinese government or from prolonged transportation restrictions. James Bruno, president of the consulting firm Chemical and Pharmaceutical Solutions, says travel restrictions are already interrupting business with Chinese suppliers. “First of all, nobody is going to be able to get to China,” he says, “so all the audits are going to be canceled.” Bruno adds that the restrictions will prolong plant closures",2020,,C&EN Global Enterprise,3005804754,#809,
,CZI,Artificial intelligence finds drugs that could fight the new coronavirus,10.1021/cen-09806-scicon1,,,,"Two independent groups last week reported that they had used artificial intelligence in different ways to find possible treatments for the novel coronavirus, named 2019-nCoV. On Feb. 4, researchers from the AI drug discovery company BenevolentAI and Imperial College London reported that they had used AI software to find an already-approved drug that might limit the virus’s ability to infect people (Lancet 2020, DOI: 10.1016/S0140-6736(20)30304-4). On Feb. 6, Insilico Medicine announced that its AI algorithms had designed new molecules that could stop the virus from replicating in people’s bodies. The company says it submitted a paper to the bioRxiv server, but the preprint had not been posted there as of press time. BenevolentAI’s algorithms connect molecular structure data to biomedical information about relevant receptors and diseases to find potential drug targets. The group adapted its search to newly available information about 2019-nCoV and focused on the enzyme adaptor-associated protein kinase",2020,,C&EN Global Enterprise,3006492276,#808,
,CZI,Biotech start-ups hit by coronavirus work stoppages,10.1021/cen-09807-buscon3,,,,"s the outbreak of the new coronavirus, now officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to mushroom, the related work stoppages in China have put a spotlight on Western biotech companies’ dependence on Chinese contract research organizations (CROs). The situation has prompted some start-ups to rethink their contingency plans—particularly when it comes to chemistry services. Biotech firms had anticipated delays related to the Lunar New Year holidays, and so far outbreak-related travel restrictions have extended that work gap by only a week. But as the virus spreads—according to Chinese authorities, as of Feb. 13, more than 60,100 people had been infected and nearly 1,400 had died, most of them in China—some biotech firms that rely on China are becoming nervous about how long their projects could be on hold. Much attention is on WuXi AppTec, the largest Chinese CRO.",2020,,C&EN Global Enterprise,2548087481,#1174,
,CZI,"Sanofi, BARDA team for coronavirus vaccine",10.1021/cen-09808-buscon15,,,,"Sanofi Pasteur is working with the US Biomedical Advanced Research and Development Authority (BARDA) to develop a vaccine against the novel coronavirus, known as severe acute respiratory syndrome-CoV-2, which as of Feb. 20 had infected more than 75,000 people and killed more than 2,100. Sanofi will build on work on a vaccine against SARS, another coronavirus that circulated in the early 2000s. In December 2019, BARDA awarded the firm a $226 million contract to expand manufacturing capacity for use in a potential flu pandemic. Sanofi says the new vaccine will use the same technology.",2020,,C&EN Global Enterprise,2625213092,#1881,
,CZI,Structure of novel coronavirus’s spike protein solved,10.1021/cen-09808-scicon3,,,,"n a piece of research accomplished with astonishing speed, scientists from the University of Texas at Austin and the National Institutes of Health have released a cryo-electron microscopy (cryo-EM) structure of part of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that has infected tens of thousands of people and killed more than 2,000 since the end of December (Science 2020, DOI: 10.1126/science.abb2507). The part of the virus imaged, called the spike protein, helps the virus attach to and infect human cells, and the determination of its structure comes just weeks after the virus’s genome sequence was published. The breakthrough is a huge step toward developing a vaccine against the virus as well as treatments for COVID-19, the disease that it causes, the researchers say. UT Austin’s Jason McLellan and his colleagues, who have spent many years studying other coronaviruses, had already figured out how to use select",2020,,C&EN Global Enterprise,,#1880,
,CZI,Diagnosing COVID-19,10.1021/cen-09808-scicon8,,,,"hina continues to fight the outbreak of a novel coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has infected tens of thousands and killed more than 2,100 people since the end of 2019. The outbreak’s hot spot is in the central province of Hubei, in particular, its capital city Wuhan, where there have been more than 62,000 infections and 2,029 deaths as of last week, according to the World Health Organization (WHO). There, doctors and scientists are desperately struggling to find reliable ways to diagnose infected patients to help treat them and control the spread of the virus. The struggle has involved two diagnostic options—computed tomography (CT) scans of patients’ lungs and a nucleic acid lab test—each with advantages and disadvantages. With “a suddenly rampant new virus, it is normal to have multiple test approaches,” says a virologist at the Chinese Center for Disease Control and Prevention",2020,,C&EN Global Enterprise,2095772697,#1882,
,CZI,"Coronavirus latest: children are as susceptible as adults, study suggests",10.1037/11533-000,,,,"Updates on the respiratory illness that has infected tens of thousands of people and killed thousands. Children are just as likely to get infected with the new coronavirus as adults, finds one of the most detailed studies yet published on the spread of the virus, known as SARS-CoV-2. The analysis — based on data from Shenzhen, China — provides a partial answer to one of the most pressing questions surrounding the outbreak: the role of children.",2020,Nature,Nature,653912363,#4490,
,CZI,Coronavirus latest: Scientists clash over virus name,10.1038/531426a,,,,"Some researchers in China are unhappy with the designated name for the new coronavirus, SARS-CoV-2. They worry that the use of ‘SARS-CoV’ will confuse the public and impede efforts to control the pathogen’s spread.",2020,Nature,Nature,2307634664,#827,
,CZI,Therapeutic options for the 2019 novel coronavirus (2019-nCoV),10.1038/d41573-020-00016-0,,,,"Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV, some of which are already moving into clinical trials. Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV, some of which are already moving into clinical trials.",2020,"Li, Guangdi; Clercq, Erik De",Nature Reviews Drug Discovery,3004894342,#606,
,CZI,New virus in China requires international control effort,10.1038/d41586-020-00135-z,,,,,2020,"Liu, S. L.",Nature,3000446153,#303,
,CZI,Stop the Wuhan virus,10.1038/d41586-020-00153-x,,,,"Vigilance, preparedness, speed, transparency and global coordination are now crucial to stopping a new infectious disease from becoming a global emergency. [Figure not available: see fulltext.].",2020,,Nature,3000892382,#94,
,CZI,Coronavirus latest: WHO says outbreak is not yet pandemic,10.1038/d41586-020-00154-w,,,,"Scientists are concerned about a new virus that has infected tens of thousands of people and killed more than 2,000. The virus, which emerged in the Chinese city of Wuhan in December, is a coronavirus and belongs to the same family as the pathogen that causes severe acute respiratory syndrome, or SARS. It causes a respiratory illness called COVID-19, which can spread from person to person. Here’s the latest news on the outbreak. 24 February 16:30 GMT — WHO says outbreak isn’t a pandemic At a press briefing on 24 February, the World Health Organization (WHO) said that, despite the spread of the disease, the coronavirus outbreak does not yet amount to a pandemic. “Using the word pandemic now does not fit the facts, but it may cause fear,” said WHO director-general Tedros Adhanom Ghebreyesus.",2020,,Nature,3004083679,#1875,
,CZI,Coronavirus latest: Trump requests $2.5 billion for coronavirus response,10.1038/d41586-020-00154-w,,,,"Trump requests emergency funding for coronavirus response The White House on 24 February requested up to $2.5 billion to fund the US response to COVID-19. In a letter to Congress, the Office of Management and Budget requested $1.25 billion in new funding and proposed to make up the rest by repurposing funds allocated to other programs, including $535 million assigned to the Ebola response.Updates on the respiratory illness that has infected tens of thousands of people. Updates on the respiratory illness that has infected tens of thousands of people.",2020,,Nature,2143542499,#2033,
,CZI,"Coronavirus latest: global infections pass 90,000",10.1038/d41586-020-00154-w,,,,"Updates on the respiratory illness that has infected tens of thousands of people. The number of people worldwide who have been infected with the coronavirus has passed 90,000. More than 3,000 people have died since the outbreak began in December. The vast majority of cases — more than 80,000 — have occurred in China, but around 60 other countries are now also dealing with outbreaks. Many nations are preparing for a global pandemic, as reports of cases caused by community spread — rather than importation from China — rise. South Korea, Italy and Iran are fighting the largest outbreaks outside of China.",2020,Nature,Nature,2475094986,#3142,
,CZI,Coronavirus latest: First infection detected in Africa,10.1038/d41586-020-00154-w,,,,Updates on the respiratory illness that has infected tens of thousands of people. Updates on the respiratory illness that has infected tens of thousands of people.,2020,Nature,Nature,2170093155,#1037,
,CZI,Coronavirus latest: Chinese cases spike after changes to diagnosis method,10.1038/d41586-020-00154-w,,,,Updates on the respiratory illness that has infected tens of thousands of people. Updates on the respiratory illness that has infected tens of thousands of people.,2020,,Nature,3004780074,#888,
,CZI,Coronavirus latest: deaths in China surpass SARS toll,10.1038/d41586-020-00154-w,,,,"Updates on the respiratory illness that has infected tens of thousands of people. Updates on the respiratory illness that has infected tens of thousands of people. Here’s the latest news on the outbreak. 10 February 04:30 GMT — Deaths in China surpass toll from SARS More than 900 people in China have died from the new virus, a greater number than those who died from severe acute respiratory syndrome (SARS) in the 2002–03 epidemic. That outbreak, which also originated in China, killed 774 people worldwide. The number of people in the country infected with the new coronavirus has risen to 40,171, according to the latest update from China‘s National Health Commission.",2020,Nature,Nature,3004892222,#559,
,CZI,"Coronavirus latest: infections in China pass 20,000",10.1038/d41586-020-00154-w,,,,Updates on the respiratory illness that has infected thousands of people. Updates on the respiratory illness that has infected thousands of people.,2020,,Nature,3004912618,#290,
,CZI,China coronavirus: Six questions scientists are asking,10.1038/d41586-020-00166-6,,31992880,,,2020,"Callaway, E.; Cyranoski, D.",Nature,3001388158,#237,
,CZI,Coronavirus outbreak: what's next?,10.1038/d41586-020-00236-9,,32020111,,,2020,"Lewis, Dyani",Nature,3004083679,#311,
,CZI,China coronavirus: labs worldwide scramble to analyse live samples,10.1038/d41586-020-00262-7,,32020116,,,2020,"Callaway, Ewen",Nature,3004196996,#339,
,CZI,"Calling all coronavirus researchers: keep sharing, stay open",10.1038/d41586-020-00307-x,,32020126,,,2020,,Nature,2946951548,#350,
,CZI,Coronavirus: hospitals must learn from past pandemics,10.1038/d41586-020-00354-4,,,,"Use techniques honed during the SARS, H1N1 and Ebola epidemics to separate sick and well, keep workers safe and prepare for the next outbreak, says Nahid Bhadelia Use techniques honed during the SARS, H1N1 and Ebola epidemics to separate sick and well, keep workers safe and prepare for the next outbreak, says Nahid Bhadelia",2020,"Bhadelia, Nahid",Nature,3006492624,#794,
,CZI,When will the coronavirus outbreak peak?,10.1038/d41586-020-00361-5,,,,"Officials want to know but predictions vary wildly, from now to after hundreds of millions of people are infected. Officials want to know but predictions vary wildly, from now to after hundreds of millions of people are infected.",2020,"Cyranoski, David",Nature,3005762913,#1152,
,CZI,Did pangolins spread the China coronavirus to people?,10.1038/d41586-020-00364-2,,,,Genetic sequences of viruses isolated from the scaly animals are 99% similar to that of the circulating virus — but the work is yet to be formally published. Genetic sequences of viruses isolated from the scaly animals are 99% similar to that of the circulating virus — but the work is yet to be formally published.,2020,"Cyranoski, David",Nature,3004620471,#502,
,CZI,Coronavirus: why a permanent ban on wildlife trade might not work in China,10.1038/d41586-020-00377-x,,,,,2020,"Ribeiro, Joana; Bingre, Pedro; Strubbe, Diederik; Reino, Luís",Nature,3005823408,#738,
,CZI,China: clamp down on violations of wildlife trade ban,10.1038/d41586-020-00378-w,,,,,2020,"Zhou, Z. M.; Buesching, C. D.; Macdonald, D. W.; Newman, C.",Nature,3005823978,#2482,
,CZI,Why does the coronavirus spread so easily between people?,10.1038/d41586-020-00405-w,,,,"As the number of coronavirus infections approaches 100,000 people worldwide, researchers are racing to understand what makes it spread so easily. A handful of genetic and structural analyses have identified a key feature of the virus — a protein on its surface — that might explain why it infects human cells so readily. Other groups are investigating the doorway through which the new coronavirus enters human tissues — a receptor on cell membranes. Both the cell receptor and the virus protein offer potential targets for drugs to block the pathogen, but researchers say it is too early to be sure. “Understanding transmission of the virus is key to its containment and future prevention,” says David Veesler, a structural virologist at the University of Washington in Seattle, who posted his team’s findings about the virus protein on the biomedical preprint server bioRxiv on 20 February1. The new virus spreads much more readily than the one that caused severe acute respiratory syndrome, or SARS (also a coronavirus), and has infected more than ten times the number of people who contracted SARS.",2020,"Mallapaty, Smriti",,3005674816,#4897,
,CZI,Scientists fear coronavirus spread in countries least able to contain it,10.1038/d41586-020-00405-w,,,,Concerns are rising about the virus’s potential to circulate undetected in Africa and Asia. Concerns are rising about the virus’s potential to circulate undetected in Africa and Asia.,2020,"Mallapaty, Smriti",Nature,3005674816,#751,
,CZI,Daily briefing: The potential for repurposing existing drugs to fight COVID-19 coronavirus,10.1038/d41586-020-00412-x,,,,"Time is of the essence — here’s what we’ve already got. Plus, biology’s cryo-electron microscopy boom and why Scotland is bringing back bogs. Time is of the essence — here’s what we’ve already got. Plus, biology’s cryo-electron microscopy boom and why Scotland is bringing back bogs.",2020,"Graham, Flora",Nature,2793560999,#776,
,CZI,More than 80 clinical trials launch to test coronavirus treatments,10.1038/d41586-020-00444-3,,,,"As HIV drugs, stem cells and traditional Chinese medicines vie for a chance to prove their worth, the WHO attempts to bring order to the search. As HIV drugs, stem cells and traditional Chinese medicines vie for a chance to prove their worth, the WHO attempts to bring order to the search.",2020,Nature,Nature,3005925177,#886,
,CZI,Avoid stigmatizing names for 2019 novel coronavirus,10.1038/d41586-020-00458-x,,32071450,,,2020,"Shu, Lele",Nature,3005489812,#1271,
,CZI,‘No one is allowed to go out’: your stories from the coronavirus outbreak,10.1038/d41586-020-00478-7,,,,"From laboratory closures to equipment shortages, researchers worldwide tell Nature how they have been affected by the epidemic. ‘No one is allowed out’: readers tell Nature about their experiences. The outbreak of a new coronavirus is wreaking havoc worldwide. In China, the epicentre of the epidemic, the virus has infected tens of thousands of people and killed more than 2,100. Unprecedented measures meant to contain the spread have brought millions of daily lives to a halt, and the effects have touched economies and global supply chains.",2020,"Stoye, Emma",Nature,,#1764,
,CZI,Mystery deepens over animal source of coronavirus,10.1038/d41586-020-00548-w,,32127703,,,2020,"Cyranoski, David",Nature,1504098263,#4350,
,CZI,Mystery deepens over animal source of coronavirus Podcast Extra: ‘There is lots of anxiety’: a scientist’s view from South Korea Coronavirus latest: Brazil reports first case in South America,10.1038/d41586-020-00548-w 10.1038/d41586-020-00565-9 10.1038/d41586-020-00154-w,,,,"Pangolins are a prime suspect, but a slew of genetic analyses has yet to find conclusive proof. Pangolins are a prime suspect, but a slew of genetic analyses has yet to find conclusive proof. Nick Howe speaks to chemist Bartosz Grzybowski about his experience with the coronavirus outbreak in South Korea. Nick Howe speaks to chemist Bartosz Grzybowski about his experience with the coronavirus outbreak in South Korea. A case of COVID-19 has been confirmed in Brazil — the first in South America. On 26 February, Brazil’s minister of health, Luiz Henrique Mandetta, confirmed that a man who traveled to northern Italy between 9 and 21 February has the disease. Italy’s outbreak has escalated to 324 cases and 12 deaths, according to a virus tracker maintained by Johns Hopkins University in Baltimore, Maryland.",2020,"Cyranoski, David; Grzybowski, Bartosz; Nature",Nature,,#2315,
,CZI,Time to use the p-word? Coronavirus enters dangerous new phase,10.1038/d41586-020-00551-1,,,,"As outbreaks surge worldwide, scientists fear that COVID-19 might soon become pandemic. As outbreaks surge worldwide, scientists fear that COVID-19 might soon become pandemic.",2020,"Callaway, Ewen",Nature,2031123810,#2009,
,CZI,Daily briefing: When a tiny lab accident almost leads to amputation,10.1038/d41586-020-00581-9,,,,"Three weeks ago, on the basis of genetic analyses, pangolins became the prime suspect as the animal source of the coronavirus that causes COVID-19. Further analysis of those data — alongside three other genome studies of pangolin coronaviruses — shows that although the scaly anteater is still a contender, the link is far from conclusive. Whatever the source, scientists emphasize that animals should not be vilified for their role in the outbreak. “The problem is not the animals, it’s that we get in contact with them,” says animal-behaviour researcher Sara Platto. (Nature | 4 min read)",2020,"Graham, Flora",Nature,2416623887,#2638,
,CZI,"Coronavirus nixes conference, twilight zone beckons and a faded star brightens",10.1038/d41586-020-00589-1,,,,"Coronavirus enters dangerous new phase The new coronavirus has spread to more than 70 nations and the total number of infections worldwide had passed 90,000 as Nature went to press (see ‘Rapid spread’). Researchers have warned that the surge in outbreaks outside China, where the virus emerged and most cases have occurred, means that the coronavirus is becoming unstoppable. The World Health Organization has resisted describing the situation as a pandemic. Director-general Tedros Adhanom Ghebreyesus said on 2 March that there was still a chance of containing the virus. Mike Ryan, director of the WHO’s emergencies programme, said that using the word pandemic would mean that efforts to contain and slow the spread of the virus have failed, which has proved untrue in China, Singapore and other regions. But other scientists say the surge in international cases marks a tipping point. “I think the epidemiological conditions for a pandemic are met,” says Marc Lipsitch, an infectious-disease epidemiologist at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts. He and others say that although containment measures seem to have kept outbreaks from escalating outside China for more than a month, such procedures might soon become unfeasible on a broader scale. Those efforts have involved quickly identifying infected people and their close contacts, and isolating them to prevent further transmission. “We’ve got to think more carefully about what measures might be sustainable in terms of reducing transmission without shutting down cities completely and stopping people from moving,” says Ben Cowling, an infectious-disease epidemiologist at the University of Hong Kong. The efforts include ‘social distancing’, which reduces the average chances that uninfected people will encounter an infected person. But some epidemiologists say too little is known about the outbreak to deploy this effectively.",2020,Nature,Nature,2281645967,#4920,
,CZI,Behind the scenes in the biosafety office,10.1038/d41586-020-00593-5,,,,It’s never a dull day for those tasked with keeping biological research safe for all.,2020,"Powell, Kendall",Nature,2041620149,#3902,
,CZI,Backchat: Covering coronavirus,10.1038/d41586-020-00598-0,,,,"In this edition of Backchat we take a deep dive into Nature's coverage of coronavirus. As cases climb, what are some of the challenges involved in reporting on the virus? Nick Howe hosts our roundtable discussion, with guests Ewen Callaway, Nisha Gaind, and David Cyranoski. Nick Howe hosts our roundtable discussion, with guests Ewen Callaway, Nisha Gaind, and David Cyranoski.",2020,,Nature,3004280078,#2995,
,CZI,Open peer-review platform for COVID-19 preprints,10.1038/d41586-020-00613-4,,32127711,,,2020,"Johansson, Michael A.; Saderi, Daniela",Nature,2301495257,#4351,
,CZI,Coronavirus response: a focus on containment is still apt,10.1038/d41586-020-00623-2,,32127714,,,2020,,Nature,3005352349,#4349,
,CZI,Coronavirus and the race to distribute reliable diagnostics,10.1038/d41587-020-00002-2,,,,International teams worked at speed to make tests for the virus available in record time. The medical community is rallying to develop a set of rapid and reliable molecular diagnostic tests for the new human coronavirus that appeared in China — now dubbed sudden acute respiratory syndrome coronavirus-2 (SARS-CoV-2).,2020,Nature,Nature,2094269437,#1369,
,CZI,Coronavirus puts drug repurposing on the fast track,10.1038/d41587-020-00003-1,,,,Existing antivirals and knowledge gained from the SARS and MERS outbreaks gain traction as the fastest route to fight the current coronavirus epidemic. Existing antivirals and knowledge gained from the SARS and MERS outbreaks gain traction as the fastest route to fight the current coronavirus epidemic.,2020,"Harrison, Charlotte",Nature Biotechnology,2910217498,#2629,
,CZI,Four ways researchers are responding to the COVID-19 outbreak,10.1038/d41591-020-00002-4,,,,How did researchers react so quickly to the SARS-CoV-2 epidemic? Nature Medicine has asked some key experts. How did researchers react so quickly to the SARS-CoV-2 epidemic? Nature Medicine has asked some key experts.,2020,"Keener, Amanda B.",Nature Medicine,3006304371,#1368,
,CZI,Functional Cell Receptors for Human Coronavirus,10.1038/nature12328,,,,"Viruses infect host cells by binding to receptors on thesurface of cells. Receptor is an important factor affecting host range and interspecific transmission. In December 2019, an outbreak of unexplained pneumonia occurred in Wuhan, Hubei province. The pathogen was a new coronavirus, named 2019 NovelCoronavirus (2019-nCoV) by WHO. Angiotensin-converting enzyme 2 (ACE2) was found to be the receptor of 2019-nCoV.This review provides a brief overview of human coronavirus receptors and their applications, with a view to providing references for the tracing, cross-species transmission, epidemiological analysis and antiviral and vaccine studies of 2019-nCoV.",2020,"YAN, Li; XIANG, Jie; CUI, Tianpen",Chinese Journal of Laboratory Medicine,2120967846,#2095,
,CZI,Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor,10.1038/nature12711,,24172901,,"The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history. An ongoing outbreak of Middle East respiratory syndrome coronavirus suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses, attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa, but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2). Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.",2013,"Ge, Xing-Yi; Li, Jia-Lu; Yang, Xing-Lou; Chmura, Aleksei A.; Zhu, Guangjian; Epstein, Jonathan H.; Mazet, Jonna K.; Hu, Ben; Zhang, Wei; Peng, Cheng; Zhang, Yu-Ji; Luo, Chu-Ming; Tan, Bing; Wang, Ning; Zhu, Yan; Crameri, Gary; Zhang, Shu-Yi; Wang, Lin-Fa; Daszak, Peter; Shi, Zheng-Li",Nature,1993577573,#1398,
,CZI,A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence,10.1038/nm.3985,,26552008,,"The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations. Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.",2015,"Menachery, Vineet D.; Yount, Boyd L., Jr.; Debbink, Kari; Agnihothram, Sudhakar; Gralinski, Lisa E.; Plante, Jessica A.; Graham, Rachel L.; Scobey, Trevor; Ge, Xing-Yi; Donaldson, Eric F.; Randell, Scott H.; Lanzavecchia, Antonio; Marasco, Wayne A.; Shi, Zhengli-Li; Baric, Ralph S.",Nat Med,2195009776,#1374,
,CZI,SARS and MERS: recent insights into emerging coronaviruses,10.1038/nrmicro.2016.81,,27344959,,"The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002-2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses.",2016,"de Wit, Emmie; van Doremalen, Neeltje; Falzarano, Darryl; Munster, Vincent J.",Nat Rev Microbiol,2470646526,#1404,
,CZI,NOVEL CORONAVIRUS THAT RECENTLY EMERGED IN CHINA,10.1038/s41422-020-0282-0,,32048481,,,2020,"Israeli, Eitan",Harefuah,3005212621,#767,
,CZI,Virus against virus: a potential treatment for 2019-nCov (SARS-CoV-2) and other RNA viruses,10.1038/s41422-020-0290-0,,32071427,,,2020,"Nguyen, Tuan M.; Zhang, Yang; Pandolfi, Pier Paolo",Cell Res,3004310457,#1280,
,CZI,A novel coronavirus (2019-nCoV) causing pneumonia-associated respiratory syndrome,10.1038/s41423-020-0372-4,,,,,2020,"Jiang, Shibo; Xia, Shuai; Ying, Tianlei; Lu, Lu",Cellular & Molecular Immunology AB  -The novel coronavirus was denoted as 2019-nCoV by WHO (https://www.who.int/emergencies/diseases/novel-coronavirus-2019) and the Wuhan pneumonia was named as novel coronavirus-infected pneumonia (NCIP) by Chinese scient,3005255913,#243,
,CZI,Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein,10.1038/s41423-020-0374-2,,,,,2020,"Xia, Shuai; Zhu, Yun; Liu, Meiqin; Lan, Qiaoshuai; Xu, Wei; Wu, Yanling; Ying, Tianlei; Liu, Shuwen; Shi, Zhengli; Jiang, Shibo; Lu, Lu",Cellular & Molecular Immunology,3006116465,#581,
,CZI,Epitopes for a 2019-nCoV vaccine,10.1038/s41423-020-0377-z,,,,,2020,"Lucchese, Guglielmo",Cellular & Molecular Immunology,3006116465,#1806,
,CZI,Novel antibody epitopes dominate the antigenicity of spike glycoprotein in SARS-CoV-2 compared to SARS-CoV,10.1038/s41423-020-0385-z,,,,,2020,"Zheng, Ming; Song, Lun",Cellular & Molecular Immunology,2092639010,#4320,
,CZI,Prevent and predict,10.1038/s41559-020-1150-5,,,,"As the COVID-19 outbreak continues, the next pandemic could be prevented by ending the wildlife trade and reinvesting in the monitoring of potential zoonoses.",2020,Nature,Nature Ecology & Evolution,1973735196,#1370,
,CZI,Rapid outbreak response requires trust,10.1038/s41564-020-0670-8,,,,,2020,,Nature Microbiology,2990816838,#644,
,CZI,Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses,10.1038/s41564-020-0688-y,,32094589,,"Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS-CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoonotic viral outbreak. Here, we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent SARS-CoV-2, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells, and confirm that human ACE2 is the receptor for the recently emerging SARS-CoV-2.",2020,"Letko, Michael; Marzi, Andrea; Munster, Vincent",Nat Microbiol,3006448444,#1966,
,CZI,We shouldn't worry when a virus mutates during disease outbreaks,10.1038/s41564-020-0690-4,,,,"Mutation. The word naturally conjures fears of unexpected and freakish changes. Ill-informed discussions of mutations thrive during virus outbreaks, including the ongoing spread of SARS-CoV-2. In reality, mutations are a natural part of the virus life cycle and rarely impact outbreaks dramatically.",2020,"Grubaugh, Nathan D.; Petrone, Mary E.; Holmes, Edward C.",Nature Microbiology,2030160453,#4129,
,CZI,COVID-19 and the cardiovascular system,10.1038/s41569-020-0360-5,,,,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system. Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.",2020,"Zheng, Ying-Ying; Ma, Yi-Tong; Zhang, Jin-Ying; Xie, Xiang",Nature Reviews Cardiology,2105828115,#5518,
,CZI,Outbreak of a novel coronavirus,10.1038/s41579-020-0332-0,,,,,2020,"Du Toit, A.",Nature reviews. Microbiology,3004886529,#103,
,CZI,Novel coronavirus takes flight from bats?,10.1038/s41579-020-0336-9,,,,Two recent studies provide initial insights into a novel coronavirus that is associated with an outbreak of human respiratory disease.,2020,"York, Ashley",Nature Reviews Microbiology,3006139879,#713,
,CZI,Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin,10.1038/s41586-018-0010-9,,29618817,,"Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health (1) . Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS) (2-10) . Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96-98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013-2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.",2018,"Zhou, Peng; Fan, Hang; Lan, Tian; Yang, Xing-Lou; Shi, Wei-Feng; Zhang, Wei; Zhu, Yan; Zhang, Ya-Wei; Xie, Qing-Mei; Mani, Shailendra; Zheng, Xiao-Shuang; Li, Bei; Li, Jin-Man; Guo, Hua; Pei, Guang-Qian; An, Xiao-Ping; Chen, Jun-Wei; Zhou, Ling; Mai, Kai-Jie; Wu, Zi-Xian; Li, Di; Anderson, Danielle E.; Zhang, Li-Biao; Li, Shi-Yue; Mi, Zhi-Qiang; He, Tong-Tong; Cong, Feng; Guo, Peng-Ju; Huang, Ren; Luo, Yun; Liu, Xiang-Ling; Chen, Jing; Huang, Yong; Sun, Qiang; Zhang, Xiang-Li-Lan; Wang, Yuan-Yuan; Xing, Shao-Zhen; Chen, Yan-Shan; Sun, Yuan; Li, Juan; Daszak, Peter; Wang, Lin-Fa; Shi, Zheng-Li; Tong, Yi-Gang; Ma, Jing-Yun",Nature,2794573360,#1342,
,CZI,China’s response to a novel coronavirus stands in stark contrast to the 2002 SARS outbreak response,10.1038/s41591-020-0771-1,,,,,2020,"Nkengasong, J.",Nature Medicine,,#150,
,CZI,"Communication, collaboration and cooperation can stop the 2019 coronavirus",10.1038/s41591-020-0775-x,,32015560,,,2020,,Nat Med,2095522790,#349,
,CZI,Emergence of a novel human coronavirus threatening human health,10.1038/s41591-020-0796-5,,,,"In late December 2019, a cluster of patients with ‘atypical pneumonia’ of unknown etiology was reported in Wuhan, China. A novel human coronavirus, now provisionally called ‘SARS-CoV-2’, was identified as the cause of this disease, now named ‘COVID-19’.",2020,"Poon, Leo L. M.; Peiris, Malik",Nature Medicine,2127593754,#2567,
,CZI,Author Correction: China's response to a novel coronavirus stands in stark contrast to the 2002 SARS outbreak response,10.1038/s41591-020-0816-5,,32139890,,An amendment to this paper has been published and can be accessed via a link at the top of the paper.,2020,"Nkengasong, J.",Nature medicine,3002119243,#4926,
,CZI,Early clinical manifestations and pulmonary imaging analysis of patients with Novel coronavirus pneumonia,10.1038/s41598-019-40799-w,,,,"Objective To investigate the early clinical characteristics and radiographic changes in confirmed Novel coronavirus pneumonia (NCP) and excluded NCP patients. Methods Twenty-four patients with suspected NCP admitted to Shanghai Jiao Tong University Affiliated Sixth People&rsquo;s Hospital and Jinshan Branch Hospital between January and February, 2020 were chosen as our research subjects. Early clinical features and radiographic changes were analyzed in 10 patients of confirmed NCP and 14 patients of excluded NCP. Results In the early stage, all 24 suspected patients were mild, and had normal blood gas analysis. Of 10 diagnosed patients, 50% were male. All the 10 patients had fever and fatigue, with body temperature between 37.5&#8451; and 38.5&#8451;. Only 1 patient had dry cough. 2 patients had no clear epidemiological exposure history, the other 8 had a clear epidemiological exposure, with a possible incubation period of 1-10 days. From CT imaging, lesions were characterized as ground glass shadow ( n =9), which could be unilateral ( n =1) or bilateral ( n =9), and were mainly close to the pleura ( n =9), with nodule shadow ( n =1) and without focal necrosis, and could combined with pleural effusion ( n =1. Among patients excluded NCP, all 14 patients had a clear history of epidemic exposure, with an onset time of 1 to 13 days. 12 patients had fever , including 4 with temperature &gt; 38.5&deg;C, 8 with temperature 37.3-38.5&deg;C, and 2 without fever. All patients had fatigue , 7 patients had dry cough and 2 patients had chest pain. From CT imaging, ground glass shadow appeared in 4 patients , lesions were unilateral in 10 patients and bilateral in 4 patients , and the lesions were relatively sporadic, without necrosis or pleural effusion. Conclusion 1&#65294;Not all patients with NCP have a direct history of epidemiology exposure, some patients may be infected unknowingly. 2. According to CT imaging, NCP seems to have no special manifestations different from other viral pneumonia. 3. NCP is more common among middle-aged people.",2020,"YANG, Tao; YU, Xiaona; HE, Xingxing; ZHOU, Wei; FU, Yifu; FENG, QiMing",Chinese Journal of Emergency Medicine,2921678383,#2090,
,CZI,Strategy of hospital logistic support to the battle against novel coronavirus pneumonia,10.1039/C6CS00898D,,,,"Nowadays hospitals have been at the forefront fighting against novel coronavirus pneumonia, with diagnosing and treating of patients as a top priority. In order to ensure the smooth progress of diagnosis and treatment, and prevent the occurrence of nosocomial infection, logistics support needs to make allowances for the isolation ward in time from the perspectives of logistics, facilities and equipment, and to transform the in-and-out double channels of ward access as required, thus setting up the partition of the three zones. Secondly, logistics support needs to optimize the logistics service workflow, including the medical waste management, the environmental disinfection isolation, and to optimize the catering service within hospitals to reduce the gathering and flow of personnel. Thirdly, logistics support needs to increase personnel training, and to eliminate psychological panic as well as to stabilize the logistics support team by putting logistics management cadres on the front line. Meanwhile, the logistics department needs to take over the hospital access screening work, strictly manage those who enter the hospital, maximize the safety and reliability of the logistics support within the hospital, and ensure the smooth progress of the epidemic prevention work.",2020,"CHEN, Changgui; XUAN, Junfang; HUANG, Xiaohua; SHOU, Hongyan; FU, Jinhong; WANG, Gongyi; CAI, Zhaobin",Chinese Journal of Hospital Administration,2762136999,#2342,
,CZI,Processing of the SARS-CoV pp1a/ab nsp7-10 region,10.1042/BCJ20200029,,32083638,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) is the causative agent of a respiratory disease with a high case fatality rate. During the formation of the coronaviral replication/transcription complex (RTC), essential steps include processing of the conserved polyprotein nsp7-10 region by the main protease Mpro and subsequent complex formation of the released nsp's. Here, we analyzed processing of the coronavirus nsp7-10 region using native mass spectrometry showing consumption of substrate, rise and fall of intermediate products and complexation. Importantly, there is a clear order of cleavage efficiencies, which is influenced by the polyprotein tertiary structure. Furthermore, the predominant product is an nsp7+8(2:2) hetero-tetramer with nsp8 scaffold. In conclusion, native MS, opposed to other methods, can expose the processing dynamics of viral polyproteins and the landscape of protein interactions in one set of experiments. Thereby, new insights into protein interactions, essential for generation of viral progeny, were provided, with relevance for development of antivirals.",2020,"Krichel, Boris; Falke, Sven; Hilgenfeld, Rolf; Redecke, Lars; Uetrecht, Charlotte",Biochem J,2990067939,#1601,
,CZI,COVID-19: Gastrointestinal manifestations and potential fecal-oral transmission,10.1053/j.gastro.2020.02.054,,,,,2020,"Gu, Jinyang; Han, Bing; Wang, Jian",Gastroenterology,2793345173,#4567,
,CZI,Evidence for gastrointestinal infection of SARS-CoV-2,10.1053/j.gastro.2020.02.055,,,,,2020,"Xiao, Fei; Tang, Meiwen; Zheng, Xiaobin; Liu, Ye; Li, Xiaofeng; Shan, Hong",Gastroenterology,3005688502,#4401,
,CZI,Anesthetic Management of Patients with Suspected 2019 Novel Coronavirus Infection During Emergency Procedures,10.1053/j.jvca.2020.02.039,,,,"Objectives To prevent cross-infection in the operating rooms by taking anesthesia management procedures for emergency procedures in patients with confirmed or suspected 2019-nCoV, and report clinical and anesthesia-related characteristics of these patients. Design This was a retrospective, multicenter clinical study. Setting This study used a multicenter dataset from four hospitals in Wuhan, China. Participants Patients and healthcare providers with confirmed or suspected 2019-nCoV from Jan 23 to Jan 31, 2020, at Wuhan Union Hospital, Wuhan Children's Hospital, The Central Hospital of Wuhan and Wuhan Fourth Hospital in Wuhan, China. Interventions Anesthetic management and infection control guidelines for emergency procedures in patients with suspected 2019-nCoV were drafted and applied in four hospitals in Wuhan. Measurements and Main Results Cross-infection in the operating rooms of these four hospitals has been effectively reduced by taking these measures and procedures. As for patients with laboratory-confirmed 2019-nCoV infection or suspected infection, majority of them were female (23 [62%] of 37); with a mean age of 41.0 years old (SD, 19.6; range, 4 to 78). Ten (27%) patients had chronic medical illness, including 4 (11%) with diabetes, 8 (22%) with hypertension, and 8 (22%) with digestive system disease. Twenty-five (68%) patients showed lymphopenia and 23 (62%) patients exhibited multiple mottling and ground-glass opacity on CT scanning. Conclusions Our study indicated that 2019-nCoV specific guidelines for emergency procedures in patients with confirmed or suspected 2019-nCoV may effectively prevent cross-infection in the operating rooms. Most patients with confirmed or suspected 2019-nCoV presented with fever, dry cough, and developed bilateral multiple mottling and ground-glass opacity on chest CT scans.",2020,"Zhao, Shuai; Ling, Ken; Yan, Hong; Zhong, Liang; Peng, Xiaohong; Yao, Shanglong; Huang, Jiapeng; Chen, Xiangdong",Journal of Cardiothoracic and Vascular Anesthesia,2883079614,#2485,
,CZI,Importation and Human-to-Human Transmission of a Novel Coronavirus in Vietnam,10.1056/NEJMc2001272,,,,,2020,"Phan, Lan T.; Nguyen, Thuong V.; Luong, Quang C.; Nguyen, Thinh V.; Nguyen, Hieu T.; Le, Hung Q.; Nguyen, Thuc T.; Cao, Thang M.; Pham, Quang D.",New England Journal of Medicine,3003951199,#50,
,CZI,Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany,10.1056/NEJMc2001468,,32003551,,,2020,"Rothe, C.; Schunk, M.; Sothmann, P.; Bretzel, G.; Froeschl, G.; Wallrauch, C.; Zimmer, T.; Thiel, V.; Janke, C.; Guggemos, W.; Seilmaier, M.; Drosten, C.; Vollmar, P.; Zwirglmaier, K.; Zange, S.; Wolfel, R.; Hoelscher, M.",The New England journal of medicine,3004239190,#92,
,CZI,A Locally Transmitted Case of SARS-CoV-2 Infection in Taiwan,10.1056/NEJMc2001573,,,,"On January 25, 2020, a 52-year-old woman with a history of type 2 diabetes presented with fever to an emergency department in central Taiwan. She was admitted to the hospital because of suspicion of pneumonia associated with SARS-CoV-2 infection. She had lived in Wuhan from October 21, 2019, to January 20, 2020. She returned to Taiwan from Wuhan on January 20 on an airplane. On the same day, a throat swab was obtained from another passenger on that flight; that passenger was confirmed to have the first known imported case of SARS-CoV-2 infection in Taiwan when the swab was found to be positive for the virus on January 21.",2020,"Liu, Ying-Chu; Liao, Ching-Hui; Chang, Chin-Fu; Chou, Chu-Chung; Lin, Yan-Ren",New England Journal of Medicine,3005688502,#755,
,CZI,Journey of a Thai Taxi Driver and Novel Coronavirus,10.1056/NEJMc2001621,,,,"On January 20, 2020, a 51-year-old male taxi driver had fever, cough, and myalgia and went to a local pharmacy to get unspecified over-the-counter medications. At the time, he was not aware of the emergence of SARS-CoV-2 or the illness it causes (Covid-19). As the symptoms persisted, he decided to visit a private primary care clinic in Bangkok on January 23. The body temperature was 36.8°C (98°F). The clinic physician ordered a throat swab for influenza A and B; the swab was negative for both strains. Additional medications were prescribed for treatment of the patient’s symptoms.",2020,"Pongpirul, Wannarat A.; Pongpirul, Krit; Ratnarathon, Anuttra C.; Prasithsirikul, Wisit",New England Journal of Medicine,3006119592,#743,
,CZI,SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients,10.1056/NEJMc2001737,,,,,2020,"Zou, Lirong; Ruan, Feng; Huang, Mingxing; Liang, Lijun; Huang, Huitao; Hong, Zhongsi; Yu, Jianxiang; Kang, Min; Song, Yingchao; Xia, Jinyu; Guo, Qianfang; Song, Tie; He, Jianfeng; Yen, Hui-Ling; Peiris, Malik; Wu, Jie",New England Journal of Medicine,1942354472,#1253,
,CZI,"Evidence of SARS-CoV-2 Infection in Returning Travelers from Wuhan, China",10.1056/NEJMc2001899,,,,,2020,"Hoehl, Sebastian; Berger, Annemarie; Kortenbusch, Marhild; Cinatl, Jindrich; Bojkova, Denisa; Rabenau, Holger; Behrens, Pia; Böddinghaus, Boris; Götsch, Udo; Naujoks, Frank; Neumann, Peter; Schork, Joscha; Tiarks-Jungk, Petra; Walczok, Antoni; Eickmann, Markus; Vehreschild, Maria J. G. T.; Kann, Gerrit; Wolf, Timo; Gottschalk, René; Ciesek, Sandra",New England Journal of Medicine,3006355661,#1184,
,CZI,"Another Decade, Another Coronavirus",10.1056/NEJMe2001126,,,,,2020,"Perlman, S.",The New England journal of medicine,3002715510,#154,
,CZI,Covid-19 — Navigating the Uncharted,10.1056/NEJMe2002387,,,,"In their Journal article, Li and colleagues3 provide a detailed clinical and epidemiologic description of the first 425 cases reported in the epicenter of the outbreak: the city of Wuhan in Hubei province, China. Although this information is critical in informing the appropriate response to this outbreak, as the authors point out, the study faces the limitation associated with reporting in real time the evolution of an emerging pathogen in its earliest stages. Nonetheless, a degree of clarity is emerging from this report. The median age of the patients was 59 years, with higher morbidity and mortality among the elderly and among those with coexisting conditions (similar to the situation with influenza); 56% of the patients were male. Of note, there were no cases in children younger than 15 years of age. Either children are less likely to become infected, which would have important epidemiologic implications, or their symptoms were so mild that their infection escaped detection, which has implications for the size of the denominator of total community infections.",2020,"Fauci, Anthony S.; Lane, H. Clifford; Redfield, Robert R.",New England Journal of Medicine,,#2804,
,CZI,Audio Interview: Preparing for the Spread of Covid-19,10.1056/NEJMe2003319,,32101683,,,2020,"Rubin, Eric J.; Baden, Lindsey R.; Morrissey, Stephen",N Engl J Med,3006612756,#2414,
,CZI,Audio Interview: What Clinicians Need to Know in Diagnosing and Treating Covid-19,10.1056/NEJMe2004244,,32130833,,,2020,"Rubin, Eric J.; Baden, Lindsey R.; Morrissey, Stephen",N Engl J Med,2921737714,#4456,
,CZI,Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia,10.1056/NEJMoa1211721,,23075143,,"A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.",2012,"Zaki, Ali M.; van Boheemen, Sander; Bestebroer, Theo M.; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.",N Engl J Med,2166867592,#1347,
,CZI,"A Novel Coronavirus from Patients with Pneumonia in China, 2019",10.1056/NEJMoa2001017,,31978945,,"In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed another clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).",2020,"Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.; Zhao, X.; Huang, B.; Shi, W.; Lu, R.; Niu, P.; Zhan, F.; Ma, X.; Wang, D.; Xu, W.; Wu, G.; Gao, G. F.; Tan, W.",The New England journal of medicine,3001897055,#8,
,CZI,Current status and progress of 2019 novel coronavirus pneumonia,10.1056/NEJMoa2001017,,,,"Recently, the 2019 novel coronavirus (2019-nCoV) pneumonia outbroke in Wuhan and rapidly spread to all over China and even the world. Because of the strong infectivity and various clinical symptoms, it has brought certain difficulties to the epidemic prevention and control. Currently there is no specific drug for 2019-nCoV. Previous drugs used to treat other coronaviruses may be effective, but further clinical trials remain needed. We reviewed literature on the epidemiology, etiology, clinical manifestations, imaging manifestations, laboratory examination, diagnosis, complications, treatment and outcome of 2019-nCoV pneumonia.",2020,"YANG, Xinying; MIAO, Congliang; JIN, Mengdi; ZHOU, Dandan; ZHUANG, Jinqiang; HONG, Jiang",Chinese Critical Care Medicine,3001897055,#2088,
,CZI,Report of the first cases of mother and infant infections with 2019 novel coronavirus in Xinyang City Henan Province,10.1056/NEJMoa2001191,,,,"Objective To report the first case of a neonatal pneumonia with 2019-nCoV infection, and the experience of successfully diagnosis and treatment in late pregnancy woman with novel coronavirus pneumonia (critical type) in Xinyang city. Methods The successfully diagnosis and treatment of a woman with 38 weeks singleton pregnancy complicated with novel coronavirus pneumonia (critical type), and a case of neonatal pneumonia with 2019-nCoV infection were retrospectively analyzed. Results A single male was successfully delivered at 38-week gestation of his mother by cesarean section under third level protection in operation room. The delivery woman was diagnosed with 2019-nCoV infection at day 2 of delivery. Dyspnea and severe hypoxemia soon developed, and invasive mechanical ventilation was given. After active rescue and treatment, the delivery woman had been taken off line successfully and the condition was stable. Pharyngeal swab specimen of the neonate was sent for examination 3 days after birth, and was positive for novel coronavirus nucleic acid by fluorescence reverse transcript polymerase chain reaction. Conclusion 2019-nCoV&nbsp;may be transmitted vertically from mother to child.",2020,"LI, Mengdie; XU, Ming; ZHAN, Weiqiang; HAN, Tao; ZHANG, Guosheng; LU, Yibin",Chinese Journal of Infectious Diseases,3003465021,#2207,
,CZI,First Case of 2019 Novel Coronavirus in the United States,10.1056/NEJMoa2001191,,,,"On January 19, 2020, a 35-year-old man presented to an urgent care clinic in Snohomish County, Washington, with a 4-day history of cough and subjective fever. On checking into the clinic, the patient put on a mask in the waiting room. After waiting approximately 20 minutes, he was taken into an examination room and underwent evaluation by a provider. He disclosed that he had returned to Washington State on January 15 after traveling to visit family in Wuhan, China. The patient stated that he had seen a health alert from the U.S. Centers for Disease Control and Prevention (CDC) about the novel coronavirus outbreak in China and, because of his symptoms and recent travel, decided to see a health care provider.",2020,"Holshue, Michelle L.; DeBolt, Chas; Lindquist, Scott; Lofy, Kathy H.; Wiesman, John; Bruce, Hollianne; Spitters, Christopher; Ericson, Keith; Wilkerson, Sara; Tural, Ahmet; Diaz, George; Cohn, Amanda; Fox, LeAnne; Patel, Anita; Gerber, Susan I.; Kim, Lindsay; Tong, Suxiang; Lu, Xiaoyan; Lindstrom, Steve; Pallansch, Mark A.; Weldon, William C.; Biggs, Holly M.; Uyeki, Timothy M.; Pillai, Satish K.",New England Journal of Medicine,3003465021,#127,
,CZI,"Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia",10.1056/NEJMoa2001316,,,,,2020,"Li, Qun; Guan, Xuhua; Wu, Peng; Wang, Xiaoye; Zhou, Lei; Tong, Yeqing; Ren, Ruiqi; Leung, Kathy S. M.; Lau, Eric H. Y.; Wong, Jessica Y.; Xing, Xuesen; Xiang, Nijuan; Wu, Yang; Li, Chao; Chen, Qi; Li, Dan; Liu, Tian; Zhao, Jing; Li, Man; Tu, Wenxiao; Chen, Chuding; Jin, Lianmei; Yang, Rui; Wang, Qi; Zhou, Suhua; Wang, Rui; Liu, Hui; Luo, Yingbo; Liu, Yuan; Shao, Ge; Li, Huan; Tao, Zhongfa; Yang, Yang; Deng, Zhiqiang; Liu, Boxi; Ma, Zhitao; Zhang, Yanping; Shi, Guoqing; Lam, Tommy T. Y.; Wu, Joseph T. K.; Gao, George F.; Cowling, Benjamin J.; Yang, Bo; Leung, Gabriel M.; Feng, Zijian",New England Journal of Medicine,,#57,
,CZI,Clinical Characteristics of Coronavirus Disease 2019 in China,10.1056/NEJMoa2002032,,,,"BACKGROUND Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)",2020,"Guan, Wei-jie; Ni, Zheng-yi; Hu, Yu; Liang, Wen-hua; Ou, Chun-quan; He, Jian-xing; Liu, Lei; Shan, Hong; Lei, Chun-liang; Hui, David S. C.; Du, Bin; Li, Lan-juan; Zeng, Guang; Yuen, Kwok-Yung; Chen, Ru-chong; Tang, Chun-li; Wang, Tao; Chen, Ping-yan; Xiang, Jie; Li, Shi-yue; Wang, Jin-lin; Liang, Zi-jing; Peng, Yi-xiang; Wei, Li; Liu, Yong; Hu, Ya-hua; Peng, Peng; Wang, Jian-ming; Liu, Ji-yang; Chen, Zhong; Li, Gang; Zheng, Zhi-jian; Qiu, Shao-qin; Luo, Jie; Ye, Chang-jiang; Zhu, Shao-yong; Zhong, Nan-shan",New England Journal of Medicine,3005477624,#2822,
,CZI,A Novel Coronavirus Emerging in China - Key Questions for Impact Assessment,10.1056/NEJMp2000929,,31978293,,,2020,"Munster, V. J.; Koopmans, M.; van Doremalen, N.; van Riel, D.; de Wit, E.",The New England journal of medicine,3002533507,#9,
,CZI,Escaping Pandora's Box - Another Novel Coronavirus,10.1056/NEJMp2002106,,32101660,,,2020,"Morens, David M.; Daszak, Peter; Taubenberger, Jeffery K.",N Engl J Med,2260741209,#2163,
,CZI,Defining the Epidemiology of Covid-19 — Studies Needed,10.1056/NEJMp2002125,,,,,2020,"Lipsitch, Marc; Swerdlow, David L.; Finelli, Lyn",New England Journal of Medicine,,#1287,
,CZI,Responding to Covid-19 — A Once-in-a-Century Pandemic?,10.1056/NEJMp2003762,,,,"In any crisis, leaders have two equally important responsibilities: solve the immediate problem and keep it from happening again. The Covid-19 pandemic is a case in point. We need to save lives now while also improving the way we respond to outbreaks in general. The first point is more pressing, but the second has crucial long-term consequences. The long-term challenge — improving our ability to respond to outbreaks — isn’t new. Global health experts have been saying for years that another pandemic whose speed and severity rivaled those of the 1918 influenza epidemic was a matter not of if but of when.1 The Bill and Melinda Gates Foundation has committed substantial resources in recent years to helping the world prepare for such a scenario. Now we also face an immediate crisis. In the past week, Covid-19 has started behaving a lot like the once-in-a-century pathogen we’ve been worried about. I hope it’s not that bad, but we should assume it will be until we know otherwise. There are two reasons that Covid-19 is such a threat. First, it can kill healthy adults in addition to elderly people with existing health problems. The data so far suggest that the virus has a case fatality risk around 1%; this rate would make it many times more severe than typical seasonal influenza, putting it somewhere between the 1957 influenza pandemic (0.6%) and the 1918 influenza pandemic (2%).2",2020,"Gates, Bill",New England Journal of Medicine,,#2812,
,CZI,Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection,10.1073/pnas.1922083117,,32054787,,"The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV-induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.",2020,"de Wit, Emmie; Feldmann, Friederike; Cronin, Jacqueline; Jordan, Robert; Okumura, Atsushi; Thomas, Tina; Scott, Dana; Cihlar, Tomas; Feldmann, Heinz",Proc Natl Acad Sci U S A,3006564542,#984,
,CZI,The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus,10.1074/jbc.AC120.013056,,32094225,,"Antiviral drugs for managing infections with human coronaviruses are not yet approved, posing a serious challenge to current global efforts aimed at containing the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Remdesivir (RDV) is an investigational compound with a broad spectrum of antiviral activities against RNA viruses, including SARS-CoV and Middle East respiratory syndrome (MERS-CoV). RDV is a nucleotide analog inhibitor of RNA-dependent RNA polymerases (RdRps). Here, we co-expressed the MERS-CoV nonstructural proteins nsp5, nsp7, nsp8, and nsp12 (RdRp) in insect cells as a part a polyprotein to study the mechanism of inhibition of MERS-CoV RdRp by RDV. We initially demonstrated that nsp8 and nsp12 form an active complex. The triphosphate form of the inhibitor (RDV-TP) competes with its natural counterpart ATP. Of note, the selectivity value for RDV-TP obtained here with a steady-state approach suggests that it is more efficiently incorporated than ATP and two other nucleotide analogues. Once incorporated at position i, the inhibitor caused RNA synthesis arrest at position i+3. Hence, the likely mechanism of action is delayed RNA chain termination. The additional three nucleotides may protect the inhibitor from excision by the viral 3'-5' exonuclease activity. Together, these results help to explain the high potency of RDV against RNA viruses in cell-based assays.",2020,"Gordon, Calvin J.; Tchesnokov, Egor P.; Feng, Joy Y.; Porter, Danielle P.; Gotte, Matthias",J Biol Chem,2749506538,#1988,
,CZI,A time delay dynamic system with external source for the local outbreak of 2019-nCoV,10.1080/00036811.2020.1732357,,,,"How to model the 2019 CoronaVirus (2019-nCov) spread in China is one of the most urgent and interesting problems in applied mathematics. In this paper, we propose a novel time delay dynamic system with external source to describe the trend of local outbreak for the 2019-nCoV. The external source is introduced in the newly proposed dynamic system, which can be considered as the suspected people travel to different areas. The numerical simulations exhibit the dynamic system with the external source is more reliable than the one without it, and the rate of isolation is extremely important for controlling the increase of cumulative confirmed people of 2019-nCoV. Based on our numerical simulation results with the public data, we suggest that the local government should have some more strict measures to maintain the rate of isolation. Otherwise the local cumulative confirmed people of 2019-nCoV might be out of control.",2020,"Chen, Yu; Cheng, Jin; Jiang, Yu; Liu, Keji",Applicable Analysis,3005139704,#2331,
,CZI,A serological survey of canine respiratory coronavirus in New Zealand,10.1080/00480169.2019.1667282,,,,"Aims: To determine the seroprevalence of canine respiratory coronavirus (CRCoV) in New Zealand dogs, and to explore associations with age, sex, breed, month, and geographical region of sampling and reported presence of clinical signs suggestive of respiratory disease. Methods: A total of 1,015 canine serum samples were randomly selected from submissions to a diagnostic laboratory between March and December 2014, and were analysed for CRCoV antibodies using a competitive ELISA. Logistic regression analysis was used to determine associations between seroprevalence of CRCoV and breed category, age, sex, sampling month, region, and reported health status of dogs. Results: Overall, 538/1,015 (53.0%) samples were seropositive for CRCoV, with 492/921 (53.4%) positive dogs in the North Island and 46/94 (49%) in the South Island. Age of dog, sampling month, region, and presence of abnormal respiratory signs were included in the initial logistic regression model. Seroprevalence was higher in dogs aged >= 3 compared with <= 2 years (p<0.01). The lowest seroprevalence was observed in July (30/105; 28.5%) and August (32/100; 32%), and the highest in June (74/100; 74%). Seroprevalence in dogs from Auckland was higher than in dogs from the Hawkes Bay, Manawatu, Marlborough, and Waikato regions (p<0.05). Abnormal respiratory signs (coughing, nasal discharge, or sneezing) were reported for 28/1,015 (2.8%) dogs sampled. Seroprevalence for CRCoV tended to be higher among dogs with respiratory signs (67.9 (95% CI=47.6-83.4)%) than dogs with no reported respiratory signs (52.6 (95% CI=49.5-55.7)%). Conclusions: Serological evidence of infection with CRCoV was present in more than half of the dogs tested from throughout New Zealand. Differences in CRCoV seroprevalence between regions and lack of seasonal pattern indicate that factors other than external temperatures may be important in the epidemiology of CRCoV in New Zealand.",2020,"More, G. D.; Dunowska, M.; Acke, E.; Cave, N. J.",New Zealand Veterinary Journal,2972874979,#3840,
,CZI,Coronavirus disinfection in histopathology,10.1080/01478885.2020.1734718,,,,"The 2019 Coronavirus epidemic, provisionally called 2019-nCoV, was first identified in Wuhan, China, in persons exposed to a seafood or wet market. There is an international push to contain the virus and prevent its spread. It is feasible that potentially infectious samples may be received in histopathology laboratories for diagnosis. This technical note presents disinfection procedures and histotechnology processes that should alleviate the risk of infection to laboratory staff. Using data obtained from similar coronaviruses, e.g. severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), experts are confident that 70% ethanol and 0.1% sodium hypochlorite should inactivate the virus. Formalin fixation and heating samples to 56oC, as used in routine tissue processing, were found to inactivate several coronaviruses and it is believed that 2019-nCoV would be similarly affected.",2020,"Henwood, Anthony F.",Journal of Histotechnology,2080044878,#2831,
,CZI,"Emerging novel Coronavirus (2019-nCoV) - Current scenario, evolutionary perspective based on genome analysis and recent developments",10.1080/01652176.2020.1727993,,,,"Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including man, mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade’s first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as “Public Health Emergency of International Concern” on January 30th, 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.",2020,"Malik, Yashpal Singh; Sircar, Shubhankar; Bhat, Sudipta; Sharun, Khan; Dhama, Kuldeep; Dadar, Maryam; Tiwari, Ruchi; Chaicumpa, Wanpen",Veterinary Quarterly,3004789303,#561,
,CZI,2019 novel coronavirus: an emerging global threat,10.1080/08998280.2020.1731272,,,,"The coronavirus (CoV) epidemic that began in China in December 2019 follows earlier epidemics of severe acute respiratory syndrome CoV in China and Middle East respiratory syndrome CoV in Saudi Arabia. The full genome of the 2019 novel coronavirus (2019-nCoV) has now been shared, and data have been gathered from several case series. As of February 11, 2020, there have been 45,182 laboratory-confirmed cases, the vast majority in China, with 1115 deaths, for an overall case-fatality rate of 2.5%. Cases have been confirmed in 27 countries. On average, each patient infects 2.2 other people. Symptomatic infection appears to predominantly affect adults, with a 5-day estimated incubation period between infection and symptom onset. The most common presenting symptoms are fever, cough, dyspnea, and myalgias and/or fatigue. All cases reported to date have shown radiographic evidence of pneumonia. 2019-nCoV is diagnosed by real-time reverse transcriptase polymerase chain reaction. Treatment is largely supportive, with regimens including antiviral therapy. Corticosteroids are not routinely recommended. Hand hygiene, prompt identification and isolation of suspect patients, and appropriate use of personal protective equipment are the most reliable methods to contain the epidemic",2020,"Columbus, Cristie; Brust, Karen B.; Arroliga, Alejandro C.",Baylor University Medical Center Proceedings,3003766409,#2319,
,CZI,The Effects of Social Media Use on Preventive Behaviors during Infectious Disease Outbreaks: The Mediating Role of Self-relevant Emotions and Public Risk Perception,10.1080/10410236.2020.1724639,,,,,2020,"Oh, Sang-Hwa; Lee, Seo Yoon; Han, Changhyun",Health Communication,2894148978,#1222,
,CZI,Effects of misleading media coverage on public health crisis: a case of the 2019 novel coronavirus outbreak in China,10.1080/13032917.2020.1730621,,,,"ABSTRACTThe coronavirus outbreak in Wuhan, China has sparked a global epidemic, which the World Health Organization declared a public health emergency of international concern on 31st January 2020 (Beijing time). This crisis has attracted intense media attention. Recently, some media outlets inappropriately labelled the coronavirus by race, using such headlines as ?Chinese virus pandemonium? and even suggesting ?China kids stay home.? The biased and misleading coverage presented via Western media channels has incited anger throughout the Chinese community and has placed undue stress upon Chinese individuals living outside China. This post-published review takes a tourism-focused perspective to examine findings from a quantitative study (Rodriguez-Seijas, Stohl, Hasin, & Eaton, 2015) published in 2015 in JAMA Psychiatry. The current paper highlights the potential impacts of misleading and biased media coverage on Chinese individuals? mental health. Specifically, this work considers perceived racial discrimination stemming from coronavirus as a public health crisis and the effects of such discrimination on individuals of Chinese heritage. Similarly imperative are pertinent effects on country image and destination image with respect to tourism marketing and tourist behaviour during times of crisis. By considering racism in the context of the coronavirus outbreak, this paper identifies potential avenues for relevant research in tourism and hospitality.",2020,"Wen, Jun; Aston, Joshua; Liu, Xinyi; Ying, Tianyu",Anatolia,2783117446,#1021,
,CZI,The global spread of 2019-nCoV: a molecular evolutionary analysis,10.1080/20477724.2020.1725339,,32048560,,"The global spread of the 2019-nCoV is continuing and is fast moving, as indicated by the WHO raising the risk assessment to high. In this article, we provide a preliminary phylodynamic and phylogeographic analysis of this new virus. A Maximum Clade Credibility tree has been built using the 29 available whole genome sequences of 2019-nCoV and two whole genome sequences that are highly similar sequences from Bat SARS-like Coronavirus available in GeneBank. We are able to clarify the mechanism of transmission among the countries which have provided the 2019-nCoV sequence isolates from their patients. The Bayesian phylogeographic reconstruction shows that the 2019-2020 nCoV most probably originated from the Bat SARS-like Coronavirus circulating in the Rhinolophus bat family. In agreement with epidemiological observations, the most likely geographic origin of the new outbreak was the city of Wuhan, China, where 2019-nCoV time of the most recent common ancestor emerged, according to molecular clock analysis, around November 25(th), 2019. These results, together with previously recorded epidemics, suggest a recurring pattern of periodical epizootic outbreaks due to Betacoronavirus. Moreover, our study describes the same population genetic dynamic underlying the SARS 2003 epidemic, and suggests the urgent need for the development of effective molecular surveillance strategies of Betacoronavirus among animals and Rhinolophus of the bat family.",2020,"Benvenuto, Domenico; Giovanetti, Marta; Salemi, Marco; Prosperi, Mattia; De Flora, Cecilia; Junior Alcantara, Luiz Carlos; Angeletti, Silvia; Ciccozzi, Massimo",Pathog Glob Health,3006367816,#795,
,CZI,Are we ready for the new fatal Coronavirus: scenario of Pakistan?,10.1080/21645515.2020.1724000,,,,"Scenario of Pakistan Pakistan, is the most affected countries, has experienced many diseases outbreaks and other disasters. Geographically and politically China and Pakistan are closely connected as shown in Figure 3. A large number of Chinese people are working in Pakistan on different developmental projects (China Pakistan Economic Corridor, Dams, Gawdar Port), and on the other hand many Pakistanis are residing in China carrying out their studies, business and jobs. The outbreak of coronavirus has appeared during the peak travel time when the Chinese from Pakistan and around the world are traveling to China, while the Pakistani community, especially students, are traveling back to Pakistan due to winter break. One of such case has been reported on 24 January 2020 after a person traveled from China to Pakistan on 21 January 2020 via Dubai and was diagnosed for 2019-nCoV on 24 January.3 However, the case was not notified officially by the government of Pakistan. In the depicted situation, the future is very alarming. After the ending of Chinese New Year celebrations, the Chinese will travel back to their jobs abroad, which may result in an outbreak of the fatal virus infection in Pakistan and other countries.",2020,"Ahmad, Tauseef; Khan, Muhammad; Khan, Fazal Mehmood; Hui, Jin",Human Vaccines & Immunotherapeutics,3005978769,#802,
,CZI,Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan,10.1080/22221751.2020.1719902,,,,"A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike's receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection. FAU - Chan, Jasper Fuk-Woo",,"Chan, J. F. Auid-Orcid https orcid org; Kok, K. H. Auid-Orcid https orcid org X.; Zhu, Z.; Chu, H.; To, K. K.; Yuan, S.; Yuen, K. Y.",,3003464757,#62,
,CZI,"An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies",10.1080/22221751.2020.1723441,,32005086,,,2020,"Jiang, S.; Du, L.; Shi, Z.",Emerging microbes & infections,3003788575,#136,
,CZI,RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak,10.1080/22221751.2020.1725399,,32020836,,"From December 2019, an outbreak of unusual pneumonia was reported in Wuhan with many cases linked to Huanan Seafood Market that sells seafood as well as live exotic animals. We investigated two patients who developed acute respiratory syndromes after independent contact history with this market. The two patients shared common clinical features including fever, cough, and multiple ground-glass opacities in the bilateral lung field with patchy infiltration. Here, we highlight the use of a low-input metagenomic next-generation sequencing (mNGS) approach on RNA extracted from bronchoalveolar lavage fluid (BALF). It rapidly identified a novel coronavirus (named 2019-nCoV according to World Health Organization announcement) which was the sole pathogens in the sample with very high abundance level (1.5% and 0.62% of total RNA sequenced). The entire viral genome is 29,881 nt in length (GenBank MN988668 and MN988669, Sequence Read Archive database Bioproject accession PRJNA601736) and is classified into β-coronavirus genus. Phylogenetic analysis indicates that 2019-nCoV is close to coronaviruses (CoVs) circulating in Rhinolophus (Horseshoe bats), such as 98.7% nucleotide identity to partial RdRp gene of bat coronavirus strain BtCoV/4991 (GenBank KP876546, 370 nt sequence of RdRp and lack of other genome sequence) and 87.9% nucleotide identity to bat coronavirus strain bat-SL-CoVZC45 and bat-SL-CoVZXC21. Evolutionary analysis based on ORF1a/1b, S, and N genes also suggests 2019-nCoV is more likely a novel CoV independently introduced from animals to humans.",2020,"Chen, Liangjun; Liu, Weiyong; Zhang, Qi; Xu, Ke; Ye, Guangming; Wu, Weichen; Sun, Ziyong; Liu, Fang; Wu, Kailang; Zhong, Bo; Mei, Yi; Zhang, Wenxia; Chen, Yu; Li, Yirong; Shi, Mang; Lan, Ke; Liu, Yingle",Emerg Microbes Infect,3005510968,#337,
,CZI,HIV-1 did not contribute to the 2019-nCoV genome,10.1080/22221751.2020.1727299,,32056509,,,2020,"Xiao, Chuan; Li, Xiaojun; Liu, Shuying; Sang, Yongming; Gao, Shou-Jiang; Gao, Feng",Emerg Microbes Infect,3006369964,#901,
,CZI,Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody,10.1080/22221751.2020.1729069,,32065055,,"The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 11,900 laboratory-confirmed human infections, including 259 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor-binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. These results suggest that CR3022 may have the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g. m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, implying that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.",2020,"Tian, Xiaolong; Li, Cheng; Huang, Ailing; Xia, Shuai; Lu, Sicong; Shi, Zhengli; Lu, Lu; Jiang, Shibo; Yang, Zhenlin; Wu, Yanling; Ying, Tianlei",Emerg Microbes Infect,3003227632,#1100,
,CZI,Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes,10.1080/22221751.2020.1729071,,32065057,,"In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.",2020,"Zhang, Wei; Du, Rong-Hui; Li, Bei; Zheng, Xiao-Shuang; Yang, Xing-Lou; Hu, Ben; Wang, Yan-Yi; Xiao, Geng-Fu; Yan, Bing; Shi, Zheng-Li; Zhou, Peng",Emerg Microbes Infect,2040396289,#1080,
,CZI,Public's early response to the novel coronavirus-infected pneumonia,10.1080/22221751.2020.1732232,,32122250,,,2020,"Zhan, Siyi; Yang, Ying Ying; Fu, Chuanxi",Emerg Microbes Infect,3003668884,#3254,
,CZI,Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity,10.1080/22221751.2020.1732837,,32102625,,"The novel coronavirus (2019-nCoV) infection caused pneumonia. we retrospectively analyzed the virus presence in the pharyngeal swab, blood, and the anal swab detected by real-time PCR in the clinical lab. Unexpectedly, the 2109-nCoV RNA was readily detected in the blood (6 of 57 patients) and the anal swabs (11 of 28 patients). Importantly, all of the 6 patients with detectable viral RNA in the blood cohort progressed to severe symptom stage, indicating a strong correlation of serum viral RNA with the disease severity (p-value = 0.0001). Meanwhile, 8 of the 11 patients with annal swab virus-positive was in severe clinical stage. However, the concentration of viral RNA in the anal swab (Ct value = 24 + 39) was higher than in the blood (Ct value = 34 + 39) from patient 2, suggesting that the virus might replicate in the digestive tract. Altogether, our results confirmed the presence of virus RNA in extra-pulmonary sites.",2020,"Chen, W.; Lan, Y.; Yuan, X.; Deng, X.; Li, Y.; Cai, X.; Li, L.; He, R.; Tan, Y.; Gao, M.; Tang, G.; Zhao, L.; Wang, J.; Fan, Q.; Wen, C.; Tong, Y.; Tang, Y.; Hu, F.; Li, F.; Tang, X.",Emerging microbes & infections,2487808280,#2765,
,CZI,No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2,10.1080/22221751.2020.1733440,,32102621,,,2020,"Liu, S. L.; Saif, L. J.; Weiss, S. R.; Su, L.",Emerging microbes & infections,2043547112,#2887,
,CZI,Treatment strategy for gastrointestinal tumor under the outbreak of novel coronavirus pneumonia in China,10.1089/lap.2017.0051,,,,"The outbreak of the novel coronavirus pneumonia (NCP) has become a public health emergency in China. Chinese authorities and health agencies had devoted great efforts to control this disease. As surgeons specialized in the treatment of gastrointestinal tumors, we should always be aware of the prevention for NCP and incorporate this awareness into every detail of clinical practice. For the patients with gastrointestinal tumors, pre-admission screening should be done in order to rule out NCP. Real-time RT-PCR panel and chest CT scan should be conducted for patients with fever (&gt;37.3&#8451;), travel history to Hubei Province within 14 days, or contact history with residents from Wuhan district within 14 days. Prevention measures for both medical staffs and the screen-negative admitted patients should also be enhanced because false negative is possible. Medical instruments should be properly discarded or disinfected according to standardized procedures established by the local center for disease control and prevention (CDC). Surgical operation should be reduced at a minimal level to prevent cross infection in this special period.Surgical intervention for benign tumor should be postponed. For malignant tumor, multidisciplinary therapy (MDT) is recommended and non-surgical anti-tumor therapy should be selected with higher priority. Neoadjuvant therapy is highly recommended for gastrointestinal cancer at advanced stages that meet the indications of NCCN guideline (gastric cancer T stage &ge; 2/rectal cancer T stage &ge; 3/unresectable colon cancer). Gastric or esophagogastricjunction (EGJ) malignant tumor with obstruction can be managed with gastric tube decompression or stent placement to relieve the symptoms. Transnasal enteral feeding tube intubation/percutaneous endoscopic gastrostomy could be adopted to ensure enteral nutrition supply. For colorectal malignancy with simple intestinal obstruction, stent placement can achieve a high success rate, which not only helps avoid emergency surgery, but also creates a better condition for subsequent surgery. Transcatheter arterial embolization for hemostasis is an alternative choice for gastrointestinal tumor with bleeding. However, emergency operation still must be performed for patients with acute uncontrolled bleeding, obstruction or after other alternative treatment measures fail. All cases with suspicious or confirmed with NCP must be reported to the local CDC department. All invasive intervention must be performed in a designated isolation area. Tertiary prevention measure must be adopted for all anesthetists with additional face mask or medical goggle protection to prevent respiratory droplet transmission. Preventive enterostomy is preferable in lower digestive tract surgery. Thoroughly disinfecting the operating room after surgery is necessary. Fever after surgery must be carefully differentiated whether it's caused by post-surgery abdominal infection/inflammation or NCP. Single-room isolation and related examinations should be performed according to the standard procedures. We believe that with the unprecedentedly joint efforts of doctors and patients, we will eventually win this war against NCP.",2020,"CHEN, Yonghe",Chinese Journal of Gastrointestinal Surgery,2606110885,#2332,
,CZI,Imported Novel Coronavirus Infections: Observation on Active and Passive Case Detection in Thailand,10.1089/pop.2020.0014,,,,"In December 2019, a viral disease – the novel coronavirus – emerged in China and spread widely.1 At present, the disease has already exported to many countries,2 and is becoming an important public health problem. Thailand is a Southeast Asian country that has many international flights connecting to China and there are already imported cases of the disease in Thailand. The first ex-China case of the new disease was detected in Thailand. We would like to share observations on the spread of this disease in Thailand. To date (24 January 2020), there are imported cases of novel coronavirus infections in Thailand. Of these cases, 1 patient is a Thai who returned from tourism activity in China and the others are 4 Chinese tourists. Focusing on disease detection, 4 patients were detected at health screening points at immigration posts at international airports. The Thai patient visited the physician herself after developing a fever upon returning to Thailand. Of interest, during the period of disease outbreak, active screening is done at Thai international airports and 21,374 travelers have already been screened. Active screening can detect 80% of imported cases; 20% are detected passively. Based on these data, it has been demonstrated that active screening at the airport is still a good method for detecting new emerging disease but it cannot provide 100% efficacy in case detection. The health-related self-concern of the patient is also important to help with passive case detection. Therefore, promotion of health knowledge concerning the new disease is very important for the international traveler.",2020,"Sookaromdee, Pathum; Wiwaniveitkit, Viroj",Population Health Management,2061002138,#3117,
,CZI,Anesthesia Procedure of Emergency Operation for Patients with Suspected or Confirmed COVID-19,10.1089/sur.2020.040,,32096692,,,2020,"Wen, Xianjie; Li, Yiqun",Surg Infect (Larchmt),2364907110,#1917,
,CZI,Three Emerging Coronaviruses in Two Decades,10.1093/ajcp/aqaa029,,32053148,,"In the past two decades, the world has seen three coronaviruses emerge and cause outbreaks that have caused considerable global health consternation. Coronaviruses are enveloped, nonsegmented, single-stranded, positive-sense RNA viruses that have a characteristic appearance on electron microscopy negative staining Image 1. As a matter of fact, the characteristic electron microscopy appearance was the clue to amplify and sequence nucleic acids from Dr Urbani’s (one of the health care providers who died of severe acute respiratory syndrome [SARS] in 2003) respiratory specimen using a consensus coronavirus primer.1 The sequence of the virus was significantly different from other coronaviruses known to cause human disease at the time. The virus was ultimately named SARS-CoV, as febrile patients had severe acute respiratory syndrome and could present with pneumonia and lower respiratory symptoms such as cough and dyspnea.2 The SARS-CoV outbreak started in Guangdong, China, and spread to many countries in Southeast Asia, North America, Europe, and South Africa. Transmission was primarily person to person through droplets that occurred during coughing or sneezing, through personal contact (shaking hands), or by touching contaminated surfaces. Of note, health professionals were particularly at risk of acquiring the disease, as transmission also occurred if isolation precautions were not followed and during certain procedures. The last case of SARS-CoV occurred in September 2003, after having infected over 8,000 persons and causing 774 deaths with a case fatality rate calculated at 9.5%.",2020,"Guarner, Jeannette",Am J Clin Pathol,3006290567,#879,
,CZI,Characteristics of peripheral blood leukocyte differential counts in patients with COVID-19,10.1093/ajcp/aqw151.021,,32114745,,"To investigate the early changes of peripheral blood leukocyte differential counts in patients with COVID-19. Ten patients with COVID-19 and 30 patients with other viral pneumonia (non-COVID-19) admitted to Shanghai Jiao Tong University Affiliated Sixth People's Hospital and Jinshan Branch Hospital from January 22 to February 17, 2020 were enrolled in this study. The differential counts of white blood cells were analyzed. Patients in COVID-19 group showed relatively lower absolute white blood cell (WBC) count 4.95(3.90,6.03)×10(9)/L, lymphocyte absolute count 1.20(0.98,1.50)×10(9)/L and eosinophil absolute count 0.01(0.01,0.01)×10(9)/L. Leukopenia developed in two patients(2/10), lymphocytopenia also in two patients(2/10). Seven over ten patients presented with eosinophil cytopenia. In non-COVID-19 group, absolute WBC count was 8.20 (6.78,9.03) ×10(9)/L (P<0.001), lymphocyte absolute count 1.75(1.20,2.53)×10(9)/L(P=0.036), eosinophil absolute count 0.02(0.01,0.03)×10(9)/L(P=0.05). Lymphocytopenia occurred in (16.7%) patients, eosinophil cytopenia in 16.7% patients too. In conclusion, leukopenia, lymphocytopenia and eosinophil cytopenia are more common in COVID-19 patients than those in non- COVID-19 patients.",2020,"Li, Y. X.; Wu, W.; Yang, T.; Zhou, W.; Fu, Y. M.; Feng, Q. M.; Ye, J. M.",Zhonghua Nei Ke Za Zhi,2588578963,#3058,
,CZI,Selection and Use of Respiratory Protection by Healthcare Workers to Protect from Infectious Diseases in Hospital Settings,10.1093/annweh/wxaa020,,,,"Abstract Objectives Infection control policies and guidelines recommend using facemasks and respirators to protect healthcare workers (HCWs) from respiratory infections. Common types of respirators used in healthcare settings are filtering facepiece respirators (FFRs) and powered air-purifying respirators (PAPRs). Aims of this study were to examine the current attitudes and practices of HCWs regarding the selection and use of respiratory protection and determine the acceptability of a novel PAPR. Methods In-depth interviews were undertaken with 20 HCWs from a large tertiary hospital in Sydney, Australia. Participants were fit tested with a lightweight tight-fitting half-facepiece PAPR (CleanSpace2™ Power Unit, PAF-0034, by CleanSpace Technology®) using the TSI™ Portacount quantitative fit test method. Results Interview results showed that HCWs had a limited role in the selection and use of facemasks and respirators and had been using the devices provided by the hospital. The majority of subjects had no knowledge of hospital policy for the use of facemasks and respirators, had not been trained on the use of respirators, and had not been fit tested previously. Compliance with the use of facemasks and respirators was perceived as being low and facemasks and respirators were typically used only for short periods of time. All 20 participants were successfully fit tested to the CleanSpace2™ PAPR (overall geometric mean fit factor—6768). According to the exit surveys, CleanSpace2™ PAPRs were easy to don (14/20) and doff (15/20) and comfortable to wear (14/20). Most participants believed that PAPRs provide higher protection, comfort and reusability over N95 FFR and can be used during pandemics and other high-risk situations. Conclusions HCWs should be aware of infection control policies and training should be provided on the correct use of respiratory protective devices. PAPRs can be used in hospital settings to protect HCWs from certain highly infectious and emerging pathogens, however, HCWs require adequate training on storage, use, and cleaning of PAPRs.",2020,"Chughtai, Abrar Ahmad; Seale, Holly; Rawlinson, William D.; Kunasekaran, Mohana; Macintyre, C. Raina",Annals of Work Exposures and Health,2800868152,#5147,
,CZI,Emergency management practice of novel coronavirus pneumonia in designated hospitals,10.1093/bja/aew177,,,,"At present, we are fighting against the outbreak of novel coronavirus pneumonia (NCP) in China. For the purposes of diagnosis and treatment of NCP patients, Hangzhou Xixi Hospital, as a designated hospital, make available the wards quickly, initiated the management system of public health emergencies, and established a 'tolerate admission- strict discharge' patients management program. Meanwhile, the hospital has established an emergency supply and coordinated distribution mechanism for medical protection materials, and a full-system and multi-model training system, ensuring smooth progress of the diagnosis and treatment work.",2020,"CHEN, Changgui; ZHANG, Songping; HUANG, Xiaohua; HUANG, Jinsong; CAI, Zhaobin",Chinese Journal of Hospital Administration,2480878409,#2341,
,CZI,Origin and evolution of the 2019 novel coronavirus,10.1093/cid/ciaa112,,,,"As of today, the intermediate host of 2019-nCoV has not been determined. Considering that intermediate hosts are generally mammals [5], they are likely the living mammals sold in the South China seafood market. Therefore, strengthening the monitoring of wild mammals is an urgent measure to prevent similar viruses from infecting humans in the future. More than 1,000 confirmed cases have been reported in China. The number of provinces and cities in China as well as other Downloaded from https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciaa112/5721420 by World Health Organization user on 06 February 2020 countries with confirmed cases are steadily increasing. It is necessary to further strengthen the monitoring to ensure that it will not cause diseases like Global Outbreak of 2003 SARS.",2020,"Liangsheng Zhang, Fu-ming Shen, Fei Chen, Zhenguo Lin","Clinical Infectious Diseases,",3004748218,#248,
,CZI,Consistent detection of 2019 novel coronavirus in saliva,10.1093/cid/ciaa149,,,,"The 2019-novel-coronavirus (2019-nCoV) was detected in the self-collected saliva of 91.7% (11/12) of patients. Serial saliva viral load monitoring generally showed a declining trend. Live virus was detected in saliva by viral culture. Saliva is a promising non-invasive specimen for diagnosis, monitoring, and infection control in patients with 2019-nCoV infection.",2020,"To, Kelvin Kai-Wang; Tsang, Owen Tak‐Yin; Chik-Yan Yip, Cyril; Chan, Kwok-Hung; Wu, Tak-Chiu; Chan, Jacky M. C.; Leung, Wai-Shing; Chik, Thomas Shiu-Hong; Choi, Chris Yau-Chung; Kandamby, Darshana H.; Lung, David Christopher; Tam, Anthony Raymond; Poon, Rosana Wing-Shan; Fung, Agnes Yim-Fong; Hung, Ivan Fan-Ngai; Cheng, Vincent Chi-Chung; Chan, Jasper Fuk-Woo; Yuen, Kwok-Yung",Clinical Infectious Diseases,3005690553,#724,
,CZI,De-isolating COVID-19 Suspect Cases: A Continuing Challenge,10.1093/cid/ciaa179,,,,"As of 15 February 2020, Singapore had screened a total of 991 suspect cases for COVID-19, of which 72 cases tested positive, 812 cases tested negative, while the remaining 107 had pending results.(1) Besides optimising sample type to increase yield, (2) the challenge in clinical management of suspect cases lies in deciding whether they may be de-isolated or if further isolation and repeat testing is required. No single indicator may be effectively used to decide on de-isolation of a suspect case. In our series of positive cases, samples from one suspect case only returned positive on the fifth repeated sample (nasopharyngeal swab), on the seventh day of clinical illness. Current evidence suggests that transmission of COVID-19 may be possible even from asymptomatic contacts,(3) and polymerase chain reaction (PCR) testing may not return positive initially. (4) Our suspect case was kept isolated because of a high index of clinical suspicion, with a clinically compatible illness and history of close contact with a laboratory-proven COVID-19 case. While multiplex respiratory virus panels, in general, may be helpful in the evaluation of other viral acute respiratory infections (ARIs), even the detection of an alternate respiratory pathogen may not definitively exclude COVID-19 infection. Dual infections can occur in 10- 20% of viral acute respiratory infections, as has been reported with SARS-CoV and MERSCoV. (5) In our case series, one patient with confirmed COVID-19 by nasopharyngeal aspirate also exhibited clinical symptoms compatible with dengue fever. This was laboratory confirmed by dengue NS1 antigen test. (PL Lim, personal communication).",2020,"Tay, Jun-Yang; Lim, Poh Lian; Marimuthu, Kalisvar; Sadarangani, Sapna Pradip; Ling, Li Min; Ang, Brenda Sze Peng; Chan, Monica; Leo, Yee-Sin; Vasoo, Shawn",Clinical Infectious Diseases,1556287221,#2378,
,CZI,A Case Series of children with 2019 novel coronavirus infection: clinical and epidemiological features,10.1093/cid/ciaa198,,32112072,,We first described the 2019 novel coronavirus infection in 10 children occurring in areas other than Wuhan. The coronavirus diseases in children are usually mild and epidemiological exposure is a key clue to recognize pediatric case. Prolonged virus shedding is observed in respiratory tract and feces at the convalescent stage.,2020,"Cai, J.; Xu, J.; Lin, D.; Yang, Z.; Xu, L.; Qu, Z.; Zhang, Y.; Zhang, H.; Jia, R.; Liu, P.; Wang, X.; Ge, Y.; Xia, A.; Tian, H.; Chang, H.; Wang, C.; Li, J.; Wang, J.; Zeng, M.",Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,3004790666,#2743,
,CZI,Clinical Characteristics of Imported Cases of COVID-19 in Jiangsu Province: A Multicenter Descriptive Study,10.1093/cid/ciaa199,,32109279,,"BACKGROUND: We aimed to report the clinical characteristics of imported coronavirus disease-19 (COVID-19) in Jiangsu Province. METHODS: We retrospectively investigated the clinical, imaging, and laboratory characteristics of confirmed cases of COVID-19 with WHO interim guidance in three Grade A hospitals of Jiangsu from Jan 22 to Feb 14, 2020. Real time RT-PCR was used to detect the new coronavirus in respiratory samples. RESULTS: Of the 80 patients infected with COVID-19, 41 patients were female, with a median age of 46.1 years. Except for 3 severe patients, the rest of the 77 patients exhibited mild or moderate symptoms. 9 patients were unconfirmed until a third-time nucleic acid test. 38 cases had a history of chronic diseases. The main clinical manifestations of the patients were fever and cough, which accounted for 63 cases (78.75%) and 51 cases (-63.75%) respectively. Only 3 patients (3.75%) showed liver dysfunction. Imaging examination showed that 55 patients (-68.75%) showed abnormal, 25 cases (31.25%) had no abnormal density shadow in the parenchyma of both lungs. Up to now, 21 cases were discharged from the hospital, and no patient died. The average length of stay for discharged patients was 8 days. CONCLUSIONS: Compared with the cases in Wuhan, the cases in Jiangsu exhibited mild or moderate symptoms and no obvious gender susceptivity. The proportion of patients having liver dysfunction and abnormal CT imaging was relatively lower than that of Wuhan. Notably, infected patients may be falsely excluded based on two consecutively negative respiratory pathogenic nucleic acid test results.",2020,"Wu, J.; Liu, J.; Zhao, X.; Liu, C.; Wang, W.; Wang, D.; Xu, W.; Zhang, C.; Yu, J.; Jiang, B.; Cao, H.; Li, L.",Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,3005679569,#2978,
,CZI,A case of 2019 Novel Coronavirus in a pregnant woman with preterm delivery,10.1093/cid/ciaa200,,32119083,,We presented a case of a 30-week pregnant woman with COVID-19 delivering a healthy baby with no evidence of COVID-19.,2020,"Wang, Xiaotong; Zhou, Zhiqiang; Zhang, Jianping; Zhu, Fengfeng; Tang, Yongyan; Shen, Xinghua",Clin Infect Dis,2066024373,#3279,
,CZI,A Well Infant with Coronavirus Disease 2019 (COVID-19) with High Viral Load,10.1093/cid/ciaa201,,,,A well 6-month-old infant with coronavirus disease 2019 (COVID-19) had persistently positive nasopharyngeal swabs to day 16 of admission. This case highlights the difficulties in establishing the true incidence of COVID-19 as asymptomatic individuals can excrete the virus. These patients may play important roles in human-to-human transmission in the community.,2020,"Kam, Kai-qian; Yung, Chee Fu; Cui, Lin; Lin Tzer Pin, Raymond; Mak, Tze Minn; Maiwald, Matthias; Li, Jiahui; Chong, Chia Yin; Nadua, Karen; Tan, Natalie Woon Hui; Thoon, Koh Cheng",Clinical Infectious Diseases,3005657121,#2851,
,CZI,Genomic diversity of SARS-CoV-2 in Coronavirus Disease 2019 patients,10.1093/cid/ciaa203,,,,"A novel coronavirus (SARS-CoV-2) has infected more than 75,000 individuals and spread to over 20 countries. It is still unclear how fast the virus evolved and how the virus interacts with other microorganisms in the lung.We have conducted metatranscriptome sequencing for the bronchoalveolar lavage fluid of eight SARS-CoV-2 patients, 25 community-acquired pneumonia (CAP) patients, and 20 healthy controls.The median number of intra-host variants was 1-4 in SARS-CoV-2 infected patients, which ranged between 0 and 51 in different samples. The distribution of variants on genes was similar to those observed in the population data (110 sequences). However, very few intra-host variants were observed in the population as polymorphism, implying either a bottleneck or purifying selection involved in the transmission of the virus, or a consequence of the limited diversity represented in the current polymorphism data. Although current evidence did not support the transmission of intra-host variants in a person-to-person spread, the risk should not be overlooked. The microbiota in SARS-CoV-2 infected patients was similar to those in CAP, either dominated by the pathogens or with elevated levels of oral and upper respiratory commensal bacteria.SARS-CoV-2 evolves in vivo after infection, which may affect its virulence, infectivity, and transmissibility. Although how the intra-host variant spreads in the population is still elusive, it is necessary to strengthen the surveillance of the viral evolution in the population and associated clinical changes.",2020,"Shen, Zijie; Xiao, Yan; Kang, Lu; Ma, Wentai; Shi, Leisheng; Zhang, Li; Zhou, Zhuo; Yang, Jing; Zhong, Jiaxin; Yang, Donghong; Guo, Li; Zhang, Guoliang; Li, Hongru; Xu, Yu; Chen, Mingwei; Gao, Zhancheng; Wang, Jianwei; Ren, Lili; Li, Mingkun",Clinical Infectious Diseases,3006645647,#3950,
,CZI,A glimpse into the origins of genetic diversity in SARS-CoV-2,10.1093/cid/ciaa213,,32129842,,,2020,"Wertheim, Joel O.",Clin Infect Dis,2076855096,#4411,
,CZI,2019 novel coronavirus is undergoing active recombination,10.1093/cid/ciaa219,,,,"The 2019 novel coronavirus (2019-nCoV) outbreak in Wuhan since December 2019 [1] has quickly spread to twenty-five countries [2], caused more than 44,000 cases and 1,000 deaths so far [3]. The fast sharing of 2019-nCoV genomes in GISAID (https://www.gisaid.org) provides a valuable dataset for 2019-nCoV haplotype network analysis, which is crucial for transmission and evolutionary track surveillance and secondary outbreak prevention. We called single-nucleotide variations (SNVs) for all the 84 2019-nCov genomes in GISAID using MN908947 as the reference. Genomes with same SNVs are grouped into a haplotype (shown as a pie chart node in Fig. 1, see Tab. S1 for the accessions), then the network is constructed using the median join [4] method in popART [5]. We found the 2019-nCoV haplotype network has obvious characteristics of single origin from haplotype hap_011: first, the network is star-like, centralized on the haplotype hap_011; second, hap_011 has the largest sample size and majority of the samples are from Hubei province—where outbreak originated (Tab. S1); third, most of satellite haplotypes are also from Hubei (Fig. 1); fourth, the average collection dates of hap_011 (has 0 mutation relative to MN908947) is earlier than all other mutation groups (Fig. S1). The single origin of 2019-nCov indicates a persistent animal to human transmission is unlikely, otherwise, multiple nodes with above characteristics should be observed.",2020,"Yi, Huiguang",Clinical Infectious Diseases,2954504078,#4262,
,CZI,Racing towards the development of diagnostics for a novel coronavirus (2019-nCoV),10.1093/clinchem/hvaa038,,32031590,,,2020,"Dennis Lo, Y. M.; Chiu, Rossa W. K.",Clin Chem,3005417802,#544,
,CZI,"Emergence of a Novel Coronavirus Disease (COVID-19) and the Importance of Diagnostic Testing: Why Partnership between Clinical Laboratories, Public Health Agencies, and Industry Is Essential to Control the Outbreak",10.1093/clinchem/hvaa071,,,,,2020,"Binnicker, Matthew J.",Clinical Chemistry,1963699916,#1412,
,CZI,Expert consensus on emergency surgery management for traumatic orthopedics under prevention and control of novel coronavirus pneumonia,10.1093/ejcts/ezw326,,,,"Since December 2019, novel coronavirus pneumonia (NCP) has been reported in Wuhan, Hubei Province, and spreads rapidly to all through Hubei Province and even to the whole country. The virus is 2019 novel coronavirus (2019-nCoV), never been seen previously in human, but all the population is generally susceptible. The virus spreads through many ways and is highly infectious, which brings great difficulties to the prevention and control of NCP. Based on the needs of orthopedic trauma patients for emergency surgery and review of the latest NCP diagnosis and treatment strategy and the latest principles and principles of evidence-based medicine in traumatic orthopedics, the authors put forward this expert consensus to systematically standardize the clinical pathway and protective measures of emergency surgery for orthopedic trauma patients during prevention and control of NCP and provide reference for the emergency surgical treatment of orthopedic trauma patients in hospitals at all levels.",2020,"LIU, Jing; LI, Hui; ZHOU, Wu; LIU, Guohui; ZHANG, Yingze; JIANG, Baoguo; TANG, Peifu; LIU, Guodong; WU, Xinbao; YUAN, Zhi; ZHOU, Fang; WANG, Tianbing; FU, Zhongguo; HOU, Zhiyong; SU, Jiacan; YU, Bin; SHAO, Zengwu; XIA, Tian; XIONG, Liming; FANG, Yue; WANG, Guanglin; LIN, Peng; CHEN, Yanxi; NI, Jiangdong; YANG, Lei; WANG, Dongliang; HE, Chengjian; LIU, Ximing; CHE, Biao; LI, Yaming; WANG, Junwen; CHEN, Ming; ZHAO, Meng; CAO, Faqi; SUN, Yun; MI, Bobin; LIU, Mengfei; XIONG, Yuan; XUE, Hang; HU, Liangcong; HU, Yiqiang; CHEN, Lang; YAN, Chenchen",Chinese Journal of Trauma,2572688892,#2186,
,CZI,Coronaviruses: a paradigm of new emerging zoonotic diseases,10.1093/femspd/ftaa006,,,,"A novel type of coronavirus (2019-nCoV) infecting humans appeared in Wuhan, China, at the end of December 2019. Since the identification of the outbreak the infection quickly spread involving in one month more than 31,000 confirmed cases with 638 death. Molecular analysis suggest that 2019-nCoV could be originated from bats after passaging in intermediate hosts, highlighting the high zoonotic potential of coronaviruses.",2020,"Salata, Cristiano; Calistri, Arianna; Parolin, Cristina; Palù, Giorgio",Pathogens and Disease,2097158803,#1116,
,CZI,"The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned?",10.1093/ije/dyaa033,,,,"To provide an overview of the three major deadly coronaviruses and identify areas for improvement of future preparedness plans, as well as provide a critical assessment of the risk factors and actionable items for stopping their spread, utilizing lessons learned from the first two deadly coronavirus outbreaks, as well as initial reports from the current novel coronavirus (COVID-19) epidemic in Wuhan, China.Utilizing the Centers for Disease Control and Prevention (CDC, USA) website, and a comprehensive review of PubMed literature, we obtained information regarding clinical signs and symptoms, treatment and diagnosis, transmission methods, protection methods and risk factors for Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS) and COVID-19. Comparisons between the viruses were made.Inadequate risk assessment regarding the urgency of the situation, and limited reporting on the virus within China has, in part, led to the rapid spread of COVID-19 throughout mainland China and into proximal and distant countries. Compared with SARS and MERS, COVID-19 has spread more rapidly, due in part to increased globalization and the focus of the epidemic. Wuhan, China is a large hub connecting the North, South, East and West of China via railways and a major international airport. The availability of connecting flights, the timing of the outbreak during the Chinese (Lunar) New Year, and the massive rail transit hub located in Wuhan has enabled the virus to perforate throughout China, and eventually, globally.We conclude that we did not learn from the two prior epidemics of coronavirus and were ill-prepared to deal with the challenges the COVID-19 epidemic has posed. Future research should attempt to address the uses and implications of internet of things (IoT) technologies for mapping the spread of infection.",2020,"Peeri, Noah C.; Shrestha, Nistha; Rahman, Md Siddikur; Zaki, Rafdzah; Tan, Zhengqi; Bibi, Saana; Baghbanzadeh, Mahdi; Aghamohammadi, Nasrin; Zhang, Wenyi; Haque, Ubydul",International Journal of Epidemiology,3006113744,#1525,
,CZI,A familial cluster of infection associated with the 2019 novel coronavirus indicating potential person-to-person transmission during the incubation period,10.1093/infdis/jiaa077,,,,"An ongoing outbreak of pneumonia associated with 2019 novel coronavirus (2019-nCoV) was reported in China. It is unclear if the infectivity exists during the incubation period, although a person-to-person transmission has been reported in previous studies. We report the epidemiological features of a familial cluster of four patients in Shanghai, of which one was 88 years old man with moving difficulties and was only exposed to his asymptomatic family members who developed symptoms later. The epidemiological evidence has shown a potential transmission of the 2019-nCoV during the incubation period.",2020,"Yu, Ping; Zhu, Jiang; Zhang, Zhengdong; Han, Yingjun; Huang, Lihong",The Journal of Infectious Diseases,3002539152,#1085,
,CZI,Evaluation of serologic and antigenic relationships between middle eastern respiratory syndrome coronavirus and other coronaviruses to develop vaccine platforms for the rapid response to emerging coronaviruses,10.1093/infdis/jit609,,,,"Background: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing severe acute respiratory disease and pneumonia, with 44% mortality among 136 cases to date. Design of vaccines to limit the virus spread or diagnostic tests to track newly emerging strains requires knowledge of antigenic and serologic relationships between MERS-CoV and other CoVs.Methods:  Using synthetic genomics and Venezuelan equine encephalitis virus replicons (VRPs) expressing spike and nucleocapsid proteins from MERS-CoV and other human and bat CoVs, we characterize the antigenic responses (using Western blot and enzyme-linked immunosorbent assay) and serologic responses (using neutralization assays) against 2 MERS-CoV isolates in comparison with those of other human and bat CoVs.Results:  Serologic and neutralization responses against the spike glycoprotein were primarily strain specific, with a very low level of cross-reactivity within or across subgroups. CoV N proteins within but not across subgroups share cross-reactive epitopes with MERS-CoV isolates. Our findings were validated using a convalescent-phase serum specimen from a patient infected with MERS-CoV (NA 01) and human antiserum against SARS-CoV, human CoV NL63, and human CoV OC43.Conclusions:  Vaccine design for emerging CoVs should involve chimeric spike protein containing neutralizing epitopes from multiple virus strains across subgroups to reduce immune pathology, and a diagnostic platform should include a panel of nucleocapsid and spike proteins from phylogenetically distinct CoVs.",2014,"Agnihothram, Sudhakar; Gopal, Robin; Yount Jr, Boyd L.; Donaldson, Eric F.; Menachery, Vineet D.; Graham, Rachel L.; Scobey, Trevor D.; Gralinski, Lisa E.; Denison, Mark R.; Zambon, Maria; Baric, Ralph S.; Yount, Boyd L., Jr.",Journal of Infectious Diseases,2100790445,#2452,
,CZI,"The New Coronavirus, the Current King of China",10.1093/jpids/piaa018,,,,"Coronaviruses are respiratory viruses whose appearance on electron microscopy looks like tiny crowns (Figure 1). The first coronaviruses discovered were the cause of pediatric and adult respiratory infections that were not particularly dangerous. One study from Vanderbilt found coronavirus in about 5% of samples from upper respiratory illness and 8% from lower respiratory illness [1]. Most clinically significant coronavirus infections have been found in children &lt; 2 years of age, as reviewed in this journal in 2009 [2], although adults also might suffer severe infections [3, 4]. This was the picture as late as 2018: a group of respiratory viruses that could cause serious illness in the very young, but with negligible mortality [5, 6].",2020,"Plotkin, Stanley A.",Journal of the Pediatric Infectious Diseases Society,3001897055,#1519,
,CZI,"Pneumonia of Unknown Etiology in Wuhan, China: Potential for International Spread Via Commercial Air Travel",10.1093/jtm/taaa008,,,,"There is currently an outbreak of a pneumonia of unknown etiology in Wuhan, China. While there are still several unanswered questions, we evaluate the potential for international dissemination of this disease via commercial air travel should the outbreak continue.",2020,"Bogoch, I. I.; Watts, A.; Thomas-Bachli, A.; Huber, C.; Kraemer, M. U. G.; Khan, K.",Journal of travel medicine,2999612210,#4,
,CZI,Travelers Give Wings to Novel Coronavirus (2019-nCoV),10.1093/jtm/taaa015,,,,,2020,"Wilson, Mary E.; Chen, Lin H.",Journal of Travel Medicine,3004555297,#260,
,CZI,"Isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus (2019-nCoV) outbreak",10.1093/jtm/taaa020,,,,Community containment includes measures that range from increasing social distancing to coummunity-wide quarantine. Whether these measures will be sufficient to control 2019-ncov depends on addressing some unanswered questions.,2020,"Wilder-Smith, A.; Freedman, D. O.",Journal of Travel Medicine,3006533361,#850,
,CZI,Solidarity with China as it holds the global front line during COVID-19 outbreak,10.1093/jtm/taaa027,,32125432,,,2020,"Lin, Leesa",J Travel Med,2766093046,#3352,
,CZI,Saudi Arabia`s measures to curb the COVID-19 outbreak: temporary suspension of the Umrah pilgrimage,10.1093/jtm/taaa029,,32109274,,,2020,"Ebrahim, S. H.; Memish, Z. A.",Journal of travel medicine,2516540472,#2796,
,CZI,The pandemic of social media panic travels faster than the COVID-19 outbreak,10.1093/jtm/taaa031,,32125413,,,2020,"Depoux, Anneliese; Martin, Sam; Karafillakis, Emilie; Bsd, Raman Preet; Wilder-Smith, Annelies; Larson, Heidi",J Travel Med,1501709847,#3421,
,CZI,On the origin and continuing evolution of SARS-CoV-2,10.1093/nsr/nwaa036,,,,"The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses. Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by mutations and natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses evolved into two major types (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. Although the L type (∼70%) is more prevalent than the S type (∼30%), the S type was found to be the ancestral version. Whereas the L type was more prevalent in the early stages of the outbreak in Wuhan, the frequency of the L type decreased after early January 2020. Human intervention may have placed more severe selective pressure on the L type, which might be more aggressive and spread more quickly. On the other hand, the S type, which is evolutionarily older and less aggressive, might have increased in relative frequency due to relatively weaker selective pressure. These findings strongly support an urgent need for further immediate, comprehensive studies that combine genomic data, epidemiological data, and chart records of the clinical symptoms of patients with coronavirus disease 2019 (COVID-19).",2020,"Tang, Xiaolu; Wu, Changcheng; Li, Xiang; Song, Yuhe; Yao, Xinmin; Wu, Xinkai; Duan, Yuange; Zhang, Hong; Wang, Yirong; Qian, Zhaohui; Cui, Jie; Lu, Jian",National Science Review,2377437096,#3293,
,CZI,In this issue of Occupational Medicine,10.1093/occmed/kqaa028,,,,"The recent COVID-19 outbreak in Wuhan city (Hubei Province of central China), presents significant public health challenges not only in china but across all affected countries worldwide. Koh [1] succinctly describes what coronaviruses are, and outlines six known species associated with human illnesses. The article also describes countries of origin of previous coronavirus disease outbreaks and reports number of known fatalities with associated case-fatality rates. Occupations implicated in the current COVID-19 outbreak are detailed and groups at high risk of contracting the infection e.g. healthcare workers highlighted. Social stigmatisation associated with COVID-19 is explored and suggested measures to contain the infection discussed.",2020,"Jackson-Koku, Gordon",Occupational Medicine,2891398425,#1623,
,CZI,Changes of CT Findings in a 2019 Novel Coronavirus (2019-nCoV) pneumonia patient,10.1093/qjmed/hcaa038,,32073631,,,2020,"Fang, Xin; Zhao, Ming; Li, Shuang; Yang, Lanqing; Wu, Bing",QJM,3004511262,#1312,
,CZI,Novel coronavirus (2019-nCoV): Update on 3rd Coronavirus Outbreak of 21st Century,10.1093/qjmed/hcaa081,,32125418,,,2020,"Sahu, Kamal Kant; Mishra, Ajay Kumar; Lal, Amos",QJM,3000883359,#3309,
,CZI,Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel coronavirus pneumonia,10.1097/BPO.0b013e3182840de2,,,,"A novel coronavirus pneumonia (NCP) epidemic has occurred in Wuhan, Hubei Province since December 2019, caused by a novel coronavirus (2019-nCoV) never been seen previously in human. China has imposed the strictest quarantine and closed management measures in history to control the spreading of the disease. However, severe trauma can still occur in the NCP patients. In order to standardize the emergency treatment and the infection prevention and control of severe trauma patients with hidden infection, suspected or confirmed infection of 2019-nCoV, Trauma Surgery Branch of Chinese Medical Doctors' Association organized this expert consensus. The consensus illustrated the classification of the NCP patients, severe trauma patients in need of emergency surgery, emergency surgery type, hierarchical protection for medical personnel and treatment places. Meanwhile, the consensus standardized the screening, injury severity evaluation, emergency surgical treatment strategy and postoperative management strategy of severe trauma patients during the epidemic period of NCP, providing a basis for the clinical treatment of such kind of patients.",2020,"LI, Yang; LI, Zhanfei; MAO, Qingxiang; LIU, Ding; ZHANG, Letian; YANG, Fan; XIE, Yu; ZHOU, Siru; ZHANG, Huayu; AI, Shanmu; TANG, Hao; ZHONG, Qiu; GUO, Qingshan; WANG, Yaoli; ZHANG, Weiguo; CHEN, Liyong; BAI, Xiangjun; ZHANG, Lianyang",Chinese Journal of Trauma,1976983792,#2202,
,CZI,Epidemiological and clinical characteristics of novel coronavirus infection in children: Thoughts on the diagnostic criteria of suspected cases outside Hubei Province,10.1097/INF.0b013e31806211bf,,,,"Objective To improve the diagnostic criteria of suspected cases through investigating the epidemiological and clinical manifestations of confirmed cases of new-type coronavirus infection in children. Methods We retrospective analyzed the epidemiological and clinical manifestations of 6 children with new coronavirus infection diagnosed in Chongqing Three Gorges Central Hospital from February 3, 2020 to February 15, 2020 . Compared with the diagnostic criteria of suspected cases,we summarized the problems encountered in the application of this standard in clinical work and try to put forward Suggestions for improvement. Results Among the 6 children with confirmed cases: 5 males and 1 female; 3 from Hubei Province and 3 from Wanzhou ; 6 cases of clustered onset of the family; Visiting nature: 3 cases of suspected case income, 3 cases of community or outpatient screening . Three cases with fever and / or respiratory symptoms, one of which had symptoms of diarrhea; all children's blood routine and lymphocyte counts were within the normal range; chest CT imaging except for cases No. 1 and No. 5 were in line with typical new coronavirus pneumonia signs. In addition, the remaining 3 patients had abnormal imaging but did not have the characteristics of new coronavirus pneumonia, and 1 case was normal. Comparison results:Only case 1 of all cases fully met the diagnostic criteria, and the remaining cases did not meet the diagnostic criteria of early suspected cases. Conclusion In order to improve the accuracy and practicality of the diagnosis of suspected cases in children, it is recommended to refine and standardize the diagnostic criteria of some suspected cases.",2020,"JIANG, Jianyu; DUAN, Ling; XIONG, Daoxue; FENG, Yan; LIU, Xiangjun; YU, Jie; PENG, Zhe; LANG, Chunhui",Chinese Pediatric Emergency Medicine,1981966501,#2238,
,CZI,Experience of treating severe cases of 2019 novel coronavirus pneumonia in Changde area,10.1097/JCMA.0000000000000270,,,,"Since the cluster of the 2019 novel coronavirus (2019-nCoV) pneumonia, a large number of patients gathered, the mortality of critical patients has remained high and the treatment was unclear. In this outbreak, Hunan Changde region immediately set up a hospital and intensive care unit. The patients relieved through respiratory support, hemodynamics management, nutritional support, the application of antiviral drugs, analgesic and sedation. The treatment experience in severe cases of 2019-nCov pneumonia patients were summarized as follows: in terms of respiratory support, we needed to pay attention to the advantages of high-flow nasal cannula oxygen therapy (HFNC) and the intervention of mechanical ventilation, pay attention to the ventilator parameters, and adopt prone position timely. In the aspects of fluid resuscitation and volume management, we should pay attention to the characteristics of severe patients' volume status, perform early evaluation, and clinicians should focused on hemodynamic management beside the bed. In the aspect of nutritional support and evaluation and maintenance of intestinal function, early enteral nutrition should be adopted in time. However, the trade-off between the risk of intestinal function and nutritional support in patients with mechanical ventilation and the antiviral benefits of Kaletra needed to be reevaluated, the optimized way of analgesia and sedation was adopted, at the same time, the usage and side effects of antiviral drugs should be paid attention to. We should grasp the opportunity of transportation for severe patients. It is suggested that some warning scores should be used to facilitate early recognition of patients with severe infection and then they should be earlier transferred to the designated hospital for intensive care.",2020,"JIN, Xin; FANG, Yimin; HUANG, Shaohua; LUO, Lin; QIN, Yunjian; ZHOU, Rui; PENG, Yue; YANG, Mingshi; AI, Yuhang",Chinese Critical Care Medicine,3006472059,#2235,
,CZI,The explosive epidemic outbreak of novel coronavirus disease 2019 (COVID-19) and the persistent threat of respiratory tract infectious diseases to global health security,10.1097/mcp.0000000000000676,,32132379,,,2020,"Zumla, A.; Niederman, M. S.",Current opinion in pulmonary medicine,3006645647,#5544,
,CZI,Materialism and dialectics of epidemic prevention and control: only by respecting science can we get twice the result with half the effort,10.1097/PHH.0000000000000326,,,,"The epidemic caused by 2019 novel coronavirus has been highly concerned by the international community including World Health Organization (WHO). This is an endless battle against human life and health. Never forget the past, the teacher of the future. When you think hard, draw inferences from one instance. Many phenomena and problems in the work of epidemic prevention, control and treatment are worthy of our deep reflection. We should use scientific thinking and dialectical materialism to make a practical and realistic summary. The purpose is to win the battle as soon as possible, and more importantly, to avoid repeating the same mistakes and prevent trouble before it happens.",2020,"WU, Xiukun",Chinese Critical Care Medicine,2341369673,#2119,
,CZI,Chest CT Findings in Patients with Corona Virus Disease 2019 and its Relationship with Clinical Features,10.1097/RLI.0000000000000670,,32091414,,"OBJECTIVES: To investigate the chest computed tomography (CT) findings in patients with confirmed corona virus disease 2019 (COVID-19) and to evaluate its relationship with clinical features. MATERIALS AND METHODS: Study sample consisted of 80 patients diagnosed as COVID-19 from January to February 2020. The chest CT images and clinical data were reviewed and the relationship between them was analyzed. RESULTS: Totally 80 patients diagnosed with COVID-19 were included. With regards to the clinical manifestations, 58/80 (73%) of patients had cough, 61/80 (76%) of patients had high temperature levels. The most frequent CT abnormalities observed were ground glass opacity (GGO) (73/80 cases, 91%), consolidation (50/80 cases, 63%) and interlobular septal thickening (47/80, 59%). Most of the lesions were multiple, with an average of 12±6 lung segments involved. The most common involved lung segments were the dorsal segment of the right lower lobe (69/80, 86%), the posterior basal segment of the right lower lobe (68/80, 85%), the lateral basal segment of the right lower lobe (64/80, 80%), the dorsal segment of the left lower lobe (61/80, 76%) and the posterior basal segment of the left lower lobe (65/80, 81%). The average pulmonary inflammation index (PII) value was (34%±20%) for all the patients. Correlation analysis showed that the PII value was significantly correlated with the values of lymphocyte count, monocyte count, C-reactive protein, procalcitonin, days from illness onset and body temperature (p<0.05). CONCLUSION: The common chest CT findings of COVID-19 are multiple GGO, consolidation and interlobular septal thickening in both lungs, which are mostly distributed under the pleura. There are significant correlations between the degree of pulmonary inflammation and the main clinical symptoms and laboratory results. CT plays an important role in the diagnosis and evaluation of this emerging global health emergency.",2020,"Wu, Jiong; Wu, Xiaojia; Zeng, Wenbing; Guo, Dajing; Fang, Zheng; Chen, Linli; Huang, Huizhe; Li, Chuanming",Invest Radiol,2824769728,#1744,
,CZI,The Clinical and Chest CT Features Associated with Severe and Critical COVID-19 Pneumonia,10.1097/RLI.0000000000000672,,32118615,,"OBJECTIVE: To investigate the clinical and CT features associated with severe and critical Corona Virus Disease 2019 (COVID-19) pneumonia. MATERIALS AND METHODS: Eighty-three patients with COVID-19 pneumonia including 25 severe/critical cases and 58 ordinary cases were enrolled. The chest CT images and clinical data of them were reviewed and compared. The risk factors associated with disease severity were analyzed. RESULTS: Compared with the ordinary patients, the severe/critical patients had older ages, higher incidence of comorbidities, cough, expectoration, chest pain and dyspnea. The incidences of consolidation, linear opacities, crazy-paving pattern and bronchial wall thickening in severe/critical patients were significantly higher than those of the ordinary patients. Besides, severe/critical patients showed higher incidences of lymph node enlargement, pericardial effusion and pleural effusion than the ordinary patients. The CT scores of severe/critical patients were significantly higher than those of the ordinary patients (P < 0.001). Receiver operating characteristic (ROC) curve showed that the sensitivity and specificity of CT Score were 80.0% and 82.8% respectively for the discrimination of the two types. The clinical factors of age > 50 years old, comorbidities, dyspnea, chest pain, cough, expectoration, decreased lymphocytes and increased inflammation indicators were risk factors for severe/critical COVID-19 pneumonia. CT findings of consolidation, linear opacities, crazy-paving pattern, bronchial wall thickening, high CT scores and extrapulmonary lesions were features of severe/critical COVID-19 pneumonia. CONCLUSIONS: There are significant differences in clinical symptoms, laboratory examinations and CT manifestations between the ordinary patients and the severe/critical patients. Many factors are related to the severity of the disease, which can help clinicians to judge the severity of the patient and evaluate the prognosis.",2020,"Li, Kunhua; Wu, Jiong; Wu, Faqi; Guo, Dajing; Chen, Linli; Fang, Zheng; Li, Chuanming",Invest Radiol,2145981491,#3060,
,CZI,Clinical and High-Resolution CT Features of the COVID-19 Infection: Comparison of the Initial and Follow-up Changes,10.1097/rli.0000000000000674,,32134800,,"OBJECTIVES: In late December, 2019, an outbreak of coronavirus disease (COVID-19) in Wuhan, China was caused by a novel coronavirus, newly named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to quantify severity of COVID-19 infection on High-Resolution CT and to determine its relationship with clinical parameters. MATERIALS AND METHODS: From Jan 11, 2020, to Feb 5, 2020, the clinical, laboratory and HRCT features of 42 patients (26-75 years, 25 males) with COVID-19 were analyzed. The initial and follow-up CT obtained a mean of 4.5 days and 11.6 days from the illness onset were retrospectively assessed for the severity and progression of pneumonia. Correlations among clinical parameters, initial CT features and progression of opacifications were evaluated with Spearman correlation and linear regression analysis. RESULTS: Thirty-five (83%) patients exhibited a progressive process according to CT features during the early stage from onset. Follow-up CT findings showed progressive opacifications, consolidation, interstitial thickening, fibrous strips and air bronchograms, compared to initial CT (all p<0.05). Before regular treatments, there was a moderate correlation between the days from onset and sum score of opacifications (R=0.68, p<0.01). The C-reactive protein, erythrocyte sedimentation rate and lactate dehydrogenase showed significantly positive correlation with the severity of pneumonia assessed on initial CT (R range 0.36-0.75, p<0.05). The highest temperature and the severity of opacifications assessed on initial CT were significantly related to the progression of opacifications on follow-up CT (p=0.001-0.04). CONCLUSIONS: Patients with the COVID-19 infection usually presented with typical ground-grass opacities and other CT features, which showed significant correlations with some clinical and laboratory measurements. Follow-up CT images often demonstrated progressions during the early stage from illness onset.",2020,"Xiong, Y.; Sun, D.; Liu, Y.; Fan, Y.; Zhao, L.; Li, X.; Zhu, W.",Investigative radiology,2014210218,#5341,
,CZI,Management highlights for patients with orthopedic trauma during the epidemic of Corona Virus Disease 2019,10.1097/TA.0000000000002292,,,,"Although the epidemic outbreak of Corona Virus Disease 2019 (COVID-19) restricted freecoming and going of people, it was inevitable that fracture patients, elderly ones with low-energy fracture in part ICU lar, sought medical attention. In this special situation, itwas crucial for trauma orthopaedists to do well in prevention and control of COVID-19 infection and in perioperative management of their patients as well while they went on with routine diagnosis and treatment. It was also of great significance for prognosis of the patients and prevention and control of the epidemic that orthopaedic surgeons chose proper surgical and anesthesia methods. In the process of diagnosis, treatment, nursing and rehabilitation, medical staff too was challenged by how to prevent themselves from infection and how to eliminate cluster COVID-19 transmission. This paper, from the perspectives of orthopedic surgeons, nurses and patients, expounds briefly on the management of patients with orthopedic trauma during the epidemic period of COVID-19 in a mode of multidisciplinary comprehensive interventions.",2020,"YIN, Yingchao; HOU, Zhiyong; ZHU, Yanbin; YANG, Shuhong; CHEN, Wei; WANG, Xiuli; LI, Xiuting; ZHANG, Qi; ZHANG, Yingze",Chinese Journal of Orthopaedic Trauma,2928212465,#2080,
,CZI,Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients,10.1099/0022-1317-81-11-2755,,,,"Background: A patient&rsquo;s infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. Methods: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients&rsquo; oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. Results: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0&ndash;62.0) years were analyzed. After in-hospital treatment, patients&rsquo; inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0&ndash;11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients&rsquo; stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0&ndash;16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0&ndash;4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients&rsquo; urine specimens after throat swabs were negative. Using a multiple linear regression model ( F =2.669, P =0.044, and adjusted R 2 =0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients&rsquo; stools ( t =-2.699, P =0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs 8.0 days, respectively; t =2.550, P =0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs 11 days, respectively; t =4.631, P &lt;0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results ( P &gt;0.05). Conclusions: In brief, as the clearance of viral RNA in patients&rsquo; stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.",2020,"LING, Yun; XU, Shui Bao; LIN, Yi Xiao; TIAN, Di; ZHU, Zhao Qin; DAI, Fa Hui; WU, Fan; SONG, Zhi gang; HUANG, Wei; CHEN, Jun; HU, Bi Jie; WANG, Sheng; MAO, En Qiang; ZHU, Lei; ZHANG, Wen Hong; LU, Hong Zhou",Chinese Medical Journal,2157458496,#2192,
,CZI,"Clinical analysis of 23 cases of 2019 novel coronavirus infection in Xinyang City, Henan Province",10.1101/2020.02.06.20020974,,,,"Objective To analyze the epidemiological characteristics and clinical features of the patients with 2019-nCoV infection, so as to provide basis for clinical diagnosis. Methods The epidemiology, clinical symptoms, laboratory and radiologic data of 23 patients with 2019-nCoV infection admitted to the Fifth People's Hospital of Xinyang City from January 22,2020 to January 29, 2020 were retrospectively analyzed. Results The 23 patients with 2019 nCov infection consisted of 15 men and 8 women, and the median age was 46.0 (40.5, 52.0) years (27-80 years); 9 of them had basic disease (39%), including hypertension (17%), cardiovascular diseases (17%), diabetes (9%), hypothyroidism (4%) and old tuberculosis (4%). All the 23 patients had contact history in Wuhan area or with confirmed infections. Clinical symptoms included: fever (100%), cough (70%), expectoration (43%), myalgia (26%), headache (17%) and dyspnea (17%), and the less common symptoms were diarrhea (4.3%). Blood routine test: white blood cells (WBC) &lt; 4&times;10 9 /L in 11 cases (48%), (4-10)&times;10 9 /L in 10 cases (43%), &gt;10 &times; 109/L in 2 cases (9%); lymphocytopenia in 13 cases (56%). All 23 patients had different degrees of infective lesions in chest CT examination, with 9 cases (39%) on one side and 14 cases (61%) on both sides. Classification: 19 mild cases, 4 severe cases, no critical or death case. Complications included acute respiratory distress syndrome [4 (17%)]. No case was reported with the damage of liver or kidney function and with secondary infection. Conclusions Epidemic history of contact, fever, pneumonia signs of chest CT, normal or decreased count of WBC and lymphocytopenia are the clinical basis for diagnosis of the disease. However, at present, the treatment of patients has not been completed, the effective treatment strategy and final prognosis are not clear.",2020,"XU, Ming; LI, Mengdie; ZHAN, Weiqiang; HAN, Tao; LIU, Litao; ZHANG, Guosheng; LU, Yibin",Chinese Critical Care Medicine,3005477624,#2101,
,CZI,Reconsideration on the multiple value of Behavior determining Health: in the perspective of the situation of COVID-19,10.1109/MPUL.2014.2355302,,,,"Why has the concept of behavior determining health created more and more extensive and far-reaching influence ever since it was put forward? The reason lies in its multiple values. It is of great practical significance and has important implications for long-term health care to explore and analyze in the perspective of the situation of COVID-19 its philosophical values, cultural values, methodological values, social values and the national strategic value of 'healthy China'.",2020,"ZHU, Lifang; BIE, Mingke; SONG, Guojian; YANG, Zhiyin",Chinese Journal of Behavioral Medicine and Brain Science,1979830743,#2041,
,CZI,"Gold nanoparticle&#8208;adjuvanted S protein induces a strong antigen&#8208;specific IgG response against severe acute respiratory syndrome&#8208;related coronavirus infection, but fails to induce protective antibodies and limit eosinophilic infiltration in lungs",10.1111/1348-0421.12754,,,,"The spike (S) protein of coronavirus, which binds to cellular receptors and mediates membrane fusion for cell entry, is a candidate vaccine target for blocking coronavirus infection. However, some animal studies have suggested that inadequate immunization against severe acute respiratory syndrome coronavirus (SARS&#8208;CoV) induces a lung eosinophilic immunopathology upon infection. The present study evaluated two kinds of vaccine adjuvants for use with recombinant S protein: gold nanoparticles (AuNPs), which are expected to function as both an antigen carrier and an adjuvant in immunization; and Toll&#8208;like receptor (TLR) agonists, which have previously been shown to be an effective adjuvant in an ultraviolet&#8208;inactivated SARS&#8208;CoV vaccine. All the mice immunized with more than 0.5&#8201;µg S protein without adjuvant escaped from SARS after infection with mouse&#8208;adapted SARS&#8208;CoV; however, eosinophilic infiltrations were observed in the lungs of almost all the immunized mice. The AuNP&#8208;adjuvanted protein induced a strong IgG response but failed to improve vaccine efficacy or to reduce eosinophilic infiltration because of highly allergic inflammatory responses. Whereas similar virus titers were observed in the control animals and the animals immunized with S protein with or without AuNPs, Type 1 interferon and pro&#8208;inflammatory responses were moderate in the mice treated with S protein with and without AuNPs. On the other hand, the TLR agonist&#8208;adjuvanted vaccine induced highly protective antibodies without eosinophilic infiltrations, as well as Th1/17 cytokine responses. The findings of this study will support the development of vaccines against severe pneumonia&#8208;associated coronaviruses.",2020,"Sekimukai, Hanako; Iwata; Yoshikawa, Naoko; Fukushi, Shuetsu; Tani, Hideki; Kataoka, Michiyo; Suzuki, Tadaki; Hasegawa, Hideki; Niikura, Kenichi; Arai, Katsuhiko; Nagata, Noriyo",Microbiology and Immunology,2982765016,#70,
,CZI,World Economic Prospects Monthly,10.1111/1468-0319.12472,,,,"Overview: Coronavirus to cut global growth to new lows ▀ The rapid spread of coronavirus will weaken China's GDP growth sharply in the short term, causing disruption for the rest of the world. We now expect global GDP growth to slow to just 1.9% y/y in Q1 this year and have lowered our forecast for 2020 as a whole from 2.5% to 2.3%, down from 2.6% in 2019. ▀ Prior to the coronavirus outbreak, there had been signs that the worst was over for both world trade and the manufacturing sector. However, this tentative optimism has been dashed by the current disruption. ▀ While the near-term impact of the virus is uncertain, the disruption to China will clearly be significant in Q1 ? we expect Chinese GDP growth to plunge to just 3.8% y/y. Even though growth there will rebound in Q2 and Q3, it will take time for the loss in activity to be fully recovered and we now expect GDP growth of just 5.4% for 2020 as a whole, a downward revision of 0.6pp from last month. ▀ Weaker Chinese imports and tourism and disruption to global supply chains will take a toll on the rest of the world, particularly in the Asia-Pacific region. And the shock will exacerbate the ongoing slowdown in the US and may result in the eurozone barely expanding for a second quarter running in Q1. ▀ Weaker oil demand in the short term has prompted us to lower our Brent oil price forecast. We have cut our projection for growth in crude demand in 2020 by 0.2m b/d to 0.9 mb/d and now forecast Brent crude will average $62.4pb in 2020, down from about $65pb in our January forecast. ▀ Quarterly global growth is likely to strengthen a little in H2 this year as the disruption fades and firms make up for the lost output earlier in the year and the effect of China's policy response starts to feed through. But for 2020 overall, global growth is now likely to be just 2.3%, 0.2pp weaker than previously assumed as a result of the epidemic.",2020,,Economic Outlook,39126301,#1711,
,CZI,From the frontlines of COVID-19 – How prepared are we as obstetricians: a commentary,10.1111/1471-0528.16192,,,,"Abstract The World Health Organization (WHO) has declared the outbreak of novel coronavirus (2019-nCoV) ? now known as Coronavirus Disease (COVID-19)1 - as a global health emergency. Singapore currently stands as the country with the highest number of reported cases of COVID-19 outside of China2, excluding patients on a cruise ship offshore of Japan.",2020,"Chua, Monica Shi Qi; Lee, Jill Cheng Sim; Sulaiman, Suzanna; Tan, Hak Koon",BJOG: An International Journal of Obstetrics & Gynaecology,,#4027,
,CZI,2019 novel coronavirus infection and gastrointestinal tract,10.1111/1751-2980.12851,,32096611,,"Since end of December 2019, a cluster of patients with pneumonia of unknown origin was reported from Wuhan, Hubei province, China. As of Feb 17th, 2020, statistical data show that the outbreak constitutes an epidemic threat in China, where the exponential increase in patients has reached 75114 confirmed cases, with 2239 deaths. Different from SARS-CoV (severe acute respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus) infection, the initial presentations or the chief complain of some patients with the 2019 novel coronavirus (COVID-19) were gastrointestinal symptoms. So we call upon all the first-line medical staff to be cautious and pay more attention to those untypical patients especially from the epidemic area. Besides, as the viral nucleic acids could be found in the fecal samples and anal swabs of some patients with COVID-19 infection, the possibility of fecal-oral transmission need to be took into account. Based on the previously and recently studies, we speculate that COVID-19 may have some relationship with the gut microbiota through angiotensin-converting enzyme 2 (ACE2) receptor, thus targeting gut microbiota might be a new therapeutic option for the treatment of virus-related pneumonia. This article is protected by copyright. All rights reserved.",2020,"Gao, Qin Yan; Chen, Ying Xuan; Fang, Jing Yuan",J Dig Dis,3004896587,#1991,
,CZI,The Novel Coronavirus – A Snapshot of Current Knowledge,10.1111/1751-7915.13557,,,,"Summary Another animal to human transmission of a coronavirus occurred in December 2019 on a live animal market in the Chinese city of Wuhan causing an epidemic in China, reaching now different continents. This minireview summarizes the research literature on the virological, clinical and epidemiological aspects of this epidemic published until end of February 2020.",2020,"Brüssow, Harald",Microbial Biotechnology,,#5073,
,CZI,Hospital Emergency Management Plan During the COVID-19 Epidemic,10.1111/acem.13951,,,,"Abstract The confirmed and suspected cases of the 2019 novel coronavirus disease (COVID-19) have increased not only in Wuhan, Hubei Province but also China and the world. Enormous demand for handling the COVID-19 outbreak challenged both the healthcare personnel and medical supply system. In West China Hospital, Emergency Department (ED) undertook the mission of clinical reception, primary diagnosis, and interim treatment for the suspected cases of COVID-19.",2020,"Cao, Yubin; Li, Qin; Chen, Jing; Guo, Xia; Miao, Cheng; Yang, Hui; Chen, Zihang; Li, Chunjie",Academic Emergency Medicine,2322715620,#3204,
,CZI,Editorial 58(1),10.1111/aje.12732,,,,"As I write, the world is gripped by news of a novel coronavirus sweeping across the planet. The epidemic is causing terrible anguish to many thousands of families and astounding economic damage in Asia. Whilst yet unconfirmed, several research results now point at the hunting, trade and consumption of pangolins as a likely source of the epidemic. Whether or not pangolins do finally prove to be at the origin of this particular virus, the research highlights that the possibility is very real. This may turn out to be a turning point for pangolin conservation, perhaps for the conservation of a great many other species. In 2015, the IUCN Species Survival Commission Pangolin Specialist Group reported concerns that the profound decline in Asian pangolins would lead to traffickers procuring supplies from Africa. The next five years saw their predictions largely fulfilled. Robust results from a range of research approaches showed first an increase in trade and value of pangolins within the West and central Africa and, more recently, growing international trafficking, with China and Vietnam as major destinations. In 2016, the CITES 17th Conference of Parties moved all African pangolin species onto Appendix 1. Not a single research paper published on pangolins in the past 5 years has suggested anything other than desperate jeopardy for all eight of the world’s species. All available researches point to increasing harvesting, with the rise ultimately driven by trade for profit. The plight of over‐hunted pangolins has become a rallying call for conservation over the past few years. New NGO and government funding initiatives have arisen, dedicated to research for their conservation. The dramatically steep decline of the Asian species has been written about in both Science and Nature, the most widely read scientific journals of the day, in the last few years. The pangolin, alongside the elephant, is a poster species for action against the illegal wildlife trade. However, the research community’s awareness of the impending doom has not in the least stemmed the trade. This issue contains a Short Communication reporting for the first time trade in pangolins in yet another country, South Sudan. I am unsure of what the public response to the possibility that pangolins can transmit deadly viruses will be. I hope it is to leave them alone, rather than to try to eradicate them. This Journal remains committed to improving knowledge of the African ecosystems and increasingly to reporting research that shows how they are changing in the face of our actions. This issue, as each issue, makes a new and relevant contribution to that objective.",2020,"Abernethy, Katharine",African Journal of Ecology,3000618339,#3469,
,CZI,"Initial public health response and interim clinical guidance for the 2019 novel coronavirus outbreak - United States, December 31, 2019-February 4, 2020",10.1111/ajt.15805,,32090470,,,2020,"Patel, Anita; Jernigan, Daniel B.; nCo, V. C. D. C. Response Team",Am J Transplant,3004775012,#454,
,CZI,Coronavirus Disease 2019: Implications of Emerging Infections for Transplantation,10.1111/ajt.15832,,32090448,,"The recent identification of an outbreak of 2019- novel Coronavirus is currently evolving, and the impact on transplantation is unknown. However, it is imperative that we anticipate the potential impact on the transplant community in order to avert severe consequences of this infection on both the transplant community and contacts of transplant patients.",2020,"Michaels, Marian G.; La Hoz, Ricardo M.; Danziger Isakov, Lara; Blumberg, Emily A.; Kumar, Deepali; Green, Michael; Pruett, Timothy L.; Wolfe, Cameron R.",Am J Transplant,2896660745,#1800,
,CZI,"Clinical characteristics of 140 patients infected by SARS-CoV-2 in Wuhan, China",10.1111/all.14238,,32077115,,"BACKGROUND: Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) infection has been widely spread. We aim to investigate the clinical characteristic and allergy status of patients infected by SARS-CoV-2. METHODS: Electronical medical records including demographics, clinical manifestation, comorbidities, laboratory data and radiological materials of 140 hospitalized COVID-19 patients, with confirmed result of SARS-CoV-2 viral infection were extracted and analysed. RESULTS: An approximately 1:1 ratio of male (50.7%) and female COVID-19 patients was found, with an overall median age of 57.0 years. All patients were community acquired cases. Fever (91.7%), cough (75.0%), fatigue (75.0%) and gastrointestinal symptoms (39.6%) were the most common clinical manifestations, whereas hypertension (30.0%) and diabetes mellitus (12.1%) were the most common comorbidities. Drug hypersensitivity (11.4%) and urticaria (1.4%) were self-reported by several patients. Asthma or other allergic diseases was not reported by any of the patients. Chronic obstructive pulmonary disease (COPD, 1.4%) and current smokers (1.4%) were rare. Bilateral ground glass or patchy opacity (89.6%) were the most common signs of radiological finding. Lymphopenia (75.4%) and eosinopenia (52.9%) were observed in most patients. Blood eosinophil counts correlate positively with lymphocyte counts in severe (r=0.486, p<0.001) and non-severe (r=0.469, p<0.001) patients after hospital admission. Significantly higher levels of D-dimer, C-reactive protein and procalcitonin were associated with severe patients compared to non-severe patients (all p<0.001). CONCLUSION: Detailed clinical investigation of 140 hospitalized COVID-19 cases suggest eosinopenia together with lymphopenia may be a potential indicator for diagnosis. Allergic diseases, asthma and COPD are not risk factors for SARS-CoV-2 infection. Elder age, high number of comorbidities and more prominent laboratory abnormalities were associated with severe patients.",2020,"Zhang, Jin-Jin; Dong, Xiang; Cao, Yi-Yuan; Yuan, Ya-Dong; Yang, Yi-Bin; Yan, You-Qin; Akdis, Cezmi A.; Gao, Ya-Dong",Allergy,3005079553,#1433,
,CZI,Novel corona virus disease (COVID-19) in pregnancy: What clinical recommendations to follow?,10.1111/aogs.13836,,,,"Interim guidance has been issued by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) on managing COVID-19, which include some recommendations specific to pregnant women mostly drawn on experience from previous coronavirus outbreaks.8, 9 Chinese expert recommendations for the care of pregnant women with suspected and confirmed COVID-9 were developed and disseminated in China quite early following the outbreak in Wuhan.10 These recommendations have been dynamic, evolving as more knowledge about epidemiology, pathogenesis, disease progression and clinical course among infected pregnant patients has been gathered. Limited clinical experience in managing pregnant women with COVID-19 and their neonates has been reported from China recently based on a case series of nine pregnancies with confirmed COVID-19 treated in Zhongnan Hospital of Wuhan University and 10 neonates (nine pregnancies) delivered at five different hospitals,11, 12 although many more cases (>100) of suspected or confirmed COVID-19 have been treated and delivered in several hospitals in China according to the news releases and media reports. So far, no maternal deaths have been reported. There appears to be some risk of premature rupture of membranes, preterm delivery, fetal tachycardia and fetal distress when the infection occurs in the third trimester of pregnancy. However, there is no evidence suggesting transplacental transmission based on very limited data, as the analysis of amniotic fluid, cord blood, neonatal throat swab, and breast milk samples available from six of the nine patients were found to be negative for SARS-COV-2. Whether virus shedding occurs vaginally is also not known.",2020,"Liang, Huan; Acharya, Ganesh",Acta Obstetricia et Gynecologica Scandinavica,3006645647,#4514,
,CZI,Emergency management for preventing and controlling nosocomial infection of 2019 novel coronavirus: implications for the dermatology department,10.1111/bjd.19011,,,,"Summary As of Feb 15, 2019, the novel coronavirus (2019-nCoV) has rapidly spread throughout China and across the world with more than 60,000 laboratory-confirmed cases. Due to the current lack of specific treatment and the risk of transmission during the viral incubation period, infection prevention and control of 2019-nCoV are both urgent and critical to global health. In this article, we aim to highlight the necessity of implementing protective measures, and recommend how to set proper emergency management plans for preventing and controlling nosocomial infection of 2019-nCoV in dermatology departments.",2020,"Tao, J.; Song, Z.; Yang, L.; Huang, C.; Feng, A.; Man, X.",British Journal of Dermatology,2356688126,#4435,
,CZI,The novel Chinese coronavirus (2019-nCoV) infections,10.1111/eci.13135,,,,,2020,,European Journal of Clinical Investigation,3004412595,#2706,
,CZI,The Novel Chinese Coronavirus (2019-nCoV) Infections: challenges for fighting the storm,10.1111/eci.13209,,32003000,,"Since end of December 2019, a cluster of patients with pneumonia of unknown origin was reported from Wuhan, Hubei province, China. They shared a connection with the Huanan South China Seafood Market in Wuhan, and now it has been confirmed that the disease is caused by a novel coronavirus (provisionally named 2019-nCoV). As of today (30 January 2020), 7734 cases have been confirmed in China, and 90 cases have also been cumulatively reported from Taiwan, Thailand, Vietnam, Malaysia, Nepal, Sri Lanka, Cambodia, Japan, Singapore, Republic of Korea, United Arab Emirate, United States, The Philippines, India, Australia, Canada, Finland, France, and Germany (Finland, France and Germany are the only European countries in which cases [n= 1, n = 5, and n = 4, respectively] have been reported up to date). According to the released news, the case rate fatality is 2.2% (170/7824).",2020,"Bassetti, M.; Vena, A.; Roberto Giacobbe, D.",European journal of clinical investigation,3004412595,#113,
,CZI,"A combination regimen by lopinave/litonawe (LPV/r), emtricitabine and tenofovir alafenamide fumarate (FTC/TAF) for treatment of novel coronavirus pneumonia (TARCoV)",10.1111/hiv.12833,,,,"Objective To explore the efficacy of a combination regimen by Lopinave/Litonawe (LPV/r), emtricitabine and tenofovir alafenamide fumarate (FTC/TAF) for the treatment of novel coronavirus pneumonia (NCP). Methods We design the protocol as a real world study, which includes two groups: prospective intervention cohort (T1) and historical control group (T2). For T1 group, ninety patients will be enrolled who are diagnosed as NCP. All patients in T1 group will receive standard therapies following the recommendation in the guidelines of National Commission of Health, and they will be administered an anti-virus regimen includes LPV/r and FTC/TAF. The T2 group will enroll patients who have received single regimen includes LPV/r. The major outcome is the survival rate of patients. Secondary outcomes are the time of seroconversion of RNA, ARDS progression rate and length of hospital stay. Conclusions The results of this real world study might provide clinical practitioners a high efficiency and fast antivirus regimen for NCP. In addition, the conduction of this study will accelerate screening for other new effective therapeutic method.",2020,"JIANG, Hua; WANG, Yu; WANG, Kai; YANG, Xingxiang; ZHANG, Jiancheng; DENG, Hongfei; WANG, Lu; ZENG, Jun",Chinese Journal of Emergency Medicine,3005182192,#2239,
,CZI,The world is changing fast!,10.1111/ijcp.13486,,,,"The world is changing fast! As of 9 February 2020, there now have been at least 813 deaths from a novel strain of coronavirus that is thought to have originated in Wuhan, China (2019-nCoV), at the end of 2019. These deaths are in the context of the 37 558 cases of 2019-nCov which have already been diagnosed in China and multiple other countries.1 In the United Kingdom (UK), recent research by University College London, funded by the Nuffield Foundation, has found that 1 in 20 UK teachers now report long-lasting mental health problems, illustrating a dramatic increase from around 1/100 teachers affected in this way in the 1990s.2 In the United States (US), a recent report by Accenture (Artificial Intelligence [AI]: Healthcare's new nervous system), estimates that AI in health will be worth around $6.6 billion by 2021 and that “…when combined, key clinical health AI applications can potentially create $150 billion in annual savings for the US healthcare economy by 2026.”3 What do these facts and statistics have in common? Taken together they illustrate the massive range and rate of change in health and the responsibility of healthcare globally. In this context a valid question can be asked about the role of general medical journals such as the International Journal of Clinical Practice (IJCP). Having taken over as Editor in Chief of IJCP in January this year, I have the honour of leading an internationally renowned medical journal, with a team of extremely accomplished clinician editors, published by Wiley, one of the world's leading biomedical publishers. In our rapidly changing healthcare world, IJCP is eager, committed and ideally suited to undergo a transition process as well. As a team, our view is that in a healthcare environment of seemingly ever-increasing specialisation, one key role that a Journal such as ours should move to fulfil is to publish important, high quality medical research and opinion that will inform specialist clinicians about important general medical concepts, practical insights and recent advances. Similarly, we will also aim to inform generalists about key speciality medical advances that have relevance to generalists in the provision of care to their patients. In this work a foundational aspect of our editorial approach will be rather than looking for reasons to reject submissions, to clearly identify problems with submitted research and opinion if they exist, and work closely with authors to address these issues, allowing those authors to raise the quality of their work to the highest level. In that context, as well as continuing to publish submissions from internationally important clinicians and medical researchers worldwide, we also see that IJCP should aim to specifically encourage less experienced authors who nonetheless have important information to share with the global healthcare community. In this way, IJCP will drive forward its primary function of improving global health through the dissemination of world leading medical information and debate. The world is changing fast, and IJCP has the energy and vision to change with it!",2020,"Young, Charles",International Journal of Clinical Practice,1600193582,#2076,
,CZI,"The 2019 Coronavirus: Learning Curves, Lessons, and the Weakest Link",10.1111/ijcp.13488,,32052918,,"In the space of just six weeks, a new coronavirus, from a family that historically was not viewed as a global health concern, has become daily headline news around the globe. The 21(st) century marked its arrival with the emergence of three previously unknown coronaviruses. SARS-CoV (severe acute respiratory syndrome coronavirus) was recognized in November 2002 [1, 2], MERS-CoV (Middle East respiratory syndrome coronavirus) in June 2012 [3, 4], and 2019-nCoV in December 2019 [5]. Previously, human coronaviruses, known since the 1960s, were viewed as being only marginally relevant to the clinic, except for infants, the elderly, and immunocompromised individuals [1, 6, 7].",2020,"Stein, Richard Albert",Int J Clin Pract,3006608759,#863,
,CZI,Global challenges in health and health care for nurses and midwives everywhere,10.1111/inr.12578,,32083728,,"The next decade is likely to produce any number of global challenges that will affect health and health care, including pan-national infections such as the new coronavirus COVID-19 and others that will be related to global warming. Nurses will be required to react to these events, even though they will also be affected as ordinary citizens. The future resilience of healthcare services will depend on having sufficient numbers of nurses who are adequately resourced to face the coming challenges.",2020,"Catton, H.",Int Nurs Rev,1998583863,#1682,
,CZI,Anesthesia management for cesarean section during novel coronavirous epidemic,10.1111/j.1447-0756.1995.tb00913.x,,,,"Thirty-six puerperas who underwent emergency cesarean section at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 24, 2020 to February 9, 2020, who all wore medical surgical masks, were retrospectively included in this study. Anesthesia management was performed under tertiary medical protection measures. A dedicated anesthesia equipment was separately sterilized. Narcotic drugs were used for one patient only, and disposable medical supplies were used for anesthetic supplies. Contact transmission should be avoided when a neonate required resuscitation, and early isolation and nucleic acid testing were provided for the neonates. The rate of suspected cases of novel coronavirus (2019-nCoV) was 11% , and the rate of clinically diagnosed cases was 17% before surgery. The rate of clinically diagnosed cases of 2019-nCoV was 22%, the rate of confirmed cases was 8%, and the total positive rate of diagnosis was 31% after surgery. The rate of neuraxial anesthesia was 86%, the rate of general anesthesia was 14%, the time of spinal puncture was (15&plusmn;7) min, the time of tracheal intubation under general anesthesia was (2.1&plusmn;1.3) min, the operation time was (95&plusmn;36) min, and blood loss was (276&plusmn;166) ml. The Apgar score of newborns was 8.8 &plusmn; 0.5. There was 1 neonate whose&nbsp;mother was diagnosed as having 2019 novel coronavirous disease after operation, an oropharyngeal swab specimen was obtained at 36 h of birth, and the swab was tested positive for 2019-nCoV by nucleic acid testing. As of February 10, 2020, an anesthesiologist involved in the operation was diagnosed to have infection by 2019-nCoV. In conclusion, diagnosis of 2019 novel coronavirous disease during pregnancy is more difficult, it is necessary to perform anesthesia management for cesarean section under tertiary medical protection. Although the difficulty in anesthesia operation is increased under tertiary medical protection, anesthesiologists can carry out standardized anesthesia management and guarantee the safety of maternal and infants and anesthesiologists themselves as long as they are rigorously trained and adhere to protective protocols.",2020,"ZHOU, Zhiqiang",Chinese Journal of Anesthesiology,2045416734,#2044,
,CZI,Novel coronavirus pneumonia related liver injury: etiological analysis and treatment strategy,10.1111/j.1478-3231.2006.01349.x,,,,"The outbreak of novel coronavirus pneumonia(NCP) caused by 2019&nbsp;novel coronavirus has become a global public health challenge. Some patients accompany with liver function damage in addition to the main typical respiratory symptom. Here we analyzed the clinical features, susceptible population, potential causes and therapeutic strategies of NCP related liver injury.",2020,"HU, Lilin; WANG, Weijun; ZHU, Qingjing; YANG, Ling",Chinese Journal of Hepatology,2076942479,#2261,
,CZI,Virus Isolation from the First Patient with SARS-CoV-2 in Korea,10.1111/j.1708-8305.2007.00165.x,,,,Novel coronavirus (SARS-CoV-2) is found to cause a large outbreak started from Wuhan since December 2019 in China and SARS-CoV-2 infections have been reported with epidemiological linkage to China in 25 countries until now. We isolated SARS-CoV-2 from the oropharyngeal sample obtained from the patient with the first laboratory-confirmed SARS- CoV-2 infection in Korea. Cytopathic effects of SARS-CoV-2 in the Vero cell cultures were confluent 3 days after the first blind passage of the sample. Coronavirus was confirmed with spherical particle having a fringe reminiscent of crown on transmission electron microscopy.Phylogenetic analyses of whole genome sequences showed that it clustered with other SARS- CoV-2 reported from Wuhan.,2020,"Park, Wan Beom",Journal of Korean Medical Science,1989129786,#3884,
,CZI,Preliminary prediction of the basic reproduction number of the Wuhan novel coronavirus 2019-nCoV,10.1111/jebm.12376,,32048815,,"OBJECTIVES: To estimate the basic reproduction number of the Wuhan novel coronavirus (2019-nCoV). METHODS: Based on the susceptible-exposed-infected-removed (SEIR) compartment model and the assumption that the infectious cases with symptoms occurred before 26 January, 2020 are resulted from free propagation without intervention, we estimate the basic reproduction number of 2019-nCoV according to the reported confirmed cases and suspected cases, as well as the theoretical estimated number of infected cases by other research teams, together with some epidemiological determinants learned from the severe acute respiratory syndrome (SARS). RESULTS: The basic reproduction number fall between 2.8 and 3.3 by using the real-time reports on the number of 2019-nCoV-infected cases from People's Daily in China and fall between 3.2 and 3.9 on the basis of the predicted number of infected cases from international colleagues. CONCLUSIONS: The early transmission ability of 2019-nCoV is close to or slightly higher than SARS. It is a controllable disease with moderate to high transmissibility. Timely and effective control measures are needed to prevent the further transmissions.",2020,"Zhou, Tao; Liu, Quanhui; Yang, Zimo; Liao, Jingyi; Yang, Kexin; Bai, Wei; Lu, Xin; Zhang, Wei",J Evid Based Med,3006177842,#707,
,CZI,Abnormal Coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia,10.1111/jth.14768,,,,"Abstract Background In the recent outbreak of novel coronavirus infection in Wuhan, China, significantly abnormal coagulation parameters in severe novel coronavirus pneumonia (NCP) cases were a concern. Objectives To describe the coagulation feature of patients with NCP. Methods Conventional coagulation results and outcomes of consecutive 183 patients with confirmed NCP in Tongji hospital were retrospectively analysed. Results The overall mortality was 11.5%, the non-survivors revealed significantly higher D-dimer and fibrin degradation product (FDP) levels, longer prothrombin time and activated partial thromboplastin time compared to survivors on admission (P<0.05). 71.4% of non-survivors and 0.6% survivors met the criteria of disseminated intravascular coagulation during their hospital stay. Conclusions The present study shows that abnormal coagulation results, especially markedly elevated D-dimer and FDP are common in deaths with NCP.",,"Tang, Ning; Li, Dengju; Wang, Xiong; Sun, Ziyong",Journal of Thrombosis and Haemostasis,2010736881,#1269,
,CZI,Bat-borne viruses in Africa: a critical review,10.1111/jzo.12769,,,,"Abstract In Africa, bat-borne zoonoses emerged in the past few decades resulting in large outbreaks or just sporadic spillovers. In addition, hundreds of more viruses are described without any information on zoonotic potential. We discuss important characteristics of bats including bat biology, evolution, distribution and ecology that not only make them unique among most mammals but also contribute to their potential as viral reservoirs. The detection of a virus in bats does not imply that spillover will occur and several biological, ecological and anthropogenic factors play a role in such an event. We summarize and critically analyse the current knowledge on African bats as reservoirs for corona-, filo-, paramyxo- and lyssaviruses. We highlight that important information on epidemiology, bat biology and ecology is often not available to make informed decisions on zoonotic spillover potential. Even if knowledge gaps exist, it is still important to recognize the role of bats in zoonotic disease outbreaks and implement mitigation strategies to prevent exposure to infectious agents including working safely with bats. Equally important is the crucial role of bats in various ecosystem services. This necessitates a multidisciplinary One Health approach to close knowledge gaps and ensure the development of responsible mitigation strategies to not only minimize risk of infection but also ensure conservation of the species.",,"Markotter, W.; Coertse, J.; De Vries, L.; Geldenhuys, M.; Mortlock, M.",Journal of Zoology,1980794434,#1283,
,CZI,2019_nCoV/SARS-CoV-2: rapid classification of betacoronaviruses and identification of Traditional Chinese Medicine as potential origin of zoonotic coronaviruses,10.1111/lam.13285,,32060933,,"The current outbreak of a novel severe acute respiratory syndrome-like coronavirus, 2019_nCoV(now named SARS-CoV-2), illustrated difficulties in identifying a novel coronavirus and its natural host, as the coding sequences of various Betacoronavirus species can be highly diverse. By means of whole-genome sequence comparisons, we demonstrate that the noncoding flanks of the viral genome can be used to correctly separate the recognized four betacoronavirus subspecies. The conservation would be sufficient to define target sequences that could, in theory, classify novel virus species into their subspecies. Only 253 upstream noncoding sequences of Sarbecovirus are sufficient to identify genetic similarities between species of this subgenus. Furthermore, it was investigated which bat species have commercial value in China, and would thus likely be handled for trading purposes. A number of coronavirus genomes have been published that were obtained from such bat species. These bats are used in Traditional Chinese Medicine, and their handling poses a potential risk to cause zoonotic coronavirus epidemics. SIGNIFICANCE AND IMPACT OF THE STUDY: The noncoding upstream and downstream flanks of coronavirus genomes allow for rapid classification of novel Betacoronavirus species and correct identification of genetic relationships. Although bats are the likely natural host of 2019_nCoV, the exact bat species that serves as the natural host of the virus remains as yet unknown. Chinese bat species with commercial value were identified as natural reservoirs of coronaviruses and are used in Traditional Chinese Medicine. Since their trading provides a potential risk for spreading zoonoses, a change in these practices is highly recommended.",2020,"Wassenaar, T. M.; Zou, Y.",Letters in applied microbiology,3006608991,#4187,
,CZI,Public responses to the novel 2019 coronavirus (2019-nCoV) in Japan: mental health consequences and target populations,10.1111/pcn.12988,,,,,2020,"Shigemura, Jun; Ursano, Robert J.; Morganstein, Joshua C.; Kurosawa, Mie; Benedek, David M.",Psychiatry and Clinical Neurosciences,3004837187,#496,
,CZI,Trust is a key factor in the willingness of health professionals to work during the COVID-19 outbreak: Experience from the H1N1 pandemic in Japan 2009,10.1111/pcn.12995,,,,"On May 16, 2009, Kobe City Medical Center General Hospital admitted the first domestically infected patient in Japan. The number of patients who were suspected as having H1N1 influenza grew to 1687 within two weeks. On May 27, when the mayor of Kobe city declared the emergency had subsided. The World Health Organization (WHO) declared H1N1 influenza as a pandemic on June 11, 2009. Details of this are described elsewhere4,5 . I am a psychiatrist but also worked at an outpatient unit that screened for H1N1 was worried about being infected. However, the chief of my department led the way by personally consulting at the outpatient unit, which motivated me to join as well. My experience made me conduct a cross-sectional survey about the willingness and hesitation to work during the H1N1 pandemic with 3635 employees at three core hospitals in Kobe city between June and July, 20096 .",2020,"Imai, Hissei",Psychiatry and Clinical Neurosciences,976943392,#2623,
,CZI,"MERS, SARS and other coronaviruses as causes of pneumonia",10.1111/resp.13196,,29052924,,"Human coronaviruses (HCoVs) have been considered to be relatively harmless respiratory pathogens in the past. However, after the outbreak of the severe acute respiratory syndrome (SARS) and emergence of the Middle East respiratory syndrome (MERS), HCoVs have received worldwide attention as important pathogens in respiratory tract infection. This review focuses on the epidemiology, pathogenesis and clinical characteristics among SARS-coronaviruses (CoV), MERS-CoV and other HCoV infections.",2018,"Yin, Yudong; Wunderink, Richard G.",Respirology,2766931063,#1349,
,CZI,"Novel coronavirus 2019, an emerging public health emergency",10.1111/tbed.13509,,32077206,,,2020,"Ward, Michael P.; Li, Xiangdong; Tian, Kegong",Transbound Emerg Dis,3003739945,#1468,
,CZI,The ongoing crises in China illustrate that the assessment of epidemics in isolation is no longer sufficient,10.1111/tbed.13536,,,,"Summary The interplay of simultaneous COVID-19, African swine fever, and avian influenza emergencies on global health and industries is constantly evolving and difficult to predict, and therefore warrants further scrutiny. The need for a health network of global scope for the rapid and open exchange of information needs to be strengthened in order to address ongoing and future epidemics under competing resources.",2020,"Stoffel, Carla; Schuppers, Manon; Buholzer, Patrik; Muñoz, Violeta; Lechner, Isabel; Sperling, Ulrich; Küker, Susanne; De Nardi, Marco",Transboundary and Emerging Diseases,2795682635,#5243,
,CZI,Tropical Medicine & International Health March 2020,10.1111/tmi.13254,,,,"Editorial An editorial on the COVID-19 epidemic summarizes the current knowledge about the disease and the novel SARS-CoV-2 virus. In particular, characteristics of the virus and treatment options are addressed",2020,,Tropical Medicine & International Health,3000969263,#3228,
,CZI,The Covid-19 epidemic,10.1111/tmi.13383,,,,"Abstract The current outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; previously 2019-nCoV), epi-centered in Hubei Province of the People's Republic of China, has spread to many other countries. On January 30, 2020, the WHO Emergency Committee declared a global health emergency based on growing case notification rates at Chinese and international locations. The case detection rate is changing hourly and daily and can be tracked in almost real time on website provided by Johns Hopkins University [1] and other websites. As of early February 2020, China bears the large burden of morbidity and mortality, whereas the incidence in other Asian countries, in Europe and North America remains low so far.",2020,"Velavan, Thirumalaisamy P.; Meyer, Christian G.",Tropical Medicine & International Health,3006419170,#722,
,CZI,"Inactivation of three emerging viruses - severe acute respiratory syndrome coronavirus, Crimean-Congo haemorrhagic fever virus and Nipah virus - in platelet concentrates by ultraviolet C light and in plasma by methylene blue plus visible light",10.1111/vox.12888,,,,"Background Emerging viruses like severe acute respiratory syndrome coronavirus (SARS-CoV), Crimean-Congo haemorrhagic fever virus (CCHFV) and Nipah virus (NiV) have been identified to pose a potential threat to transfusion safety. In this study, the ability of the THERAFLEX UV-Platelets and THERAFLEX MB-Plasma pathogen inactivation systems to inactivate these viruses in platelet concentrates and plasma, respectively, was investigated. Materials and methods Blood products were spiked with SARS-CoV, CCHFV or NiV, and then treated with increasing doses of UVC light (THERAFLEX UV-Platelets) or with methylene blue (MB) plus increasing doses of visible light (MB/light; THERAFLEX MB-Plasma). Samples were taken before and after treatment with each illumination dose and tested for residual infectivity. Results Treatment with half to three-fourths of the full UVC dose (0 center dot 2 J/cm(2)) reduced the infectivity of SARS-CoV (>= 3 center dot 4 log), CCHFV (>= 2 center dot 2 log) and NiV (>= 4 center dot 3 log) to the limit of detection (LOD) in platelet concentrates, and treatment with MB and a fourth of the full light dose (120 J/cm(2)) decreased that of SARS-CoV (>= 3 center dot 1 log), CCHFV (>= 3 center dot 2 log) and NiV (>= 2 center dot 7 log) to the LOD in plasma. Conclusion Our study demonstrates that both THERAFLEX UV-Platelets (UVC) and THERAFLEX MB-Plasma (MB/light) effectively reduce the infectivity of SARS-CoV, CCHFV and NiV in platelet concentrates and plasma, respectively.",2020,"Eickmann, Markus; Gravemann, Ute; Handke, Wiebke; Tolksdorf, Frank; Reichenberg, Stefan; Mueller, Thomas H.; Seltsam, Axel",Vox Sanguinis,3000244297,#4078,
,CZI,New SARS-like virus in China triggers alarm,10.1126/science.367.6475.234,,,,,2020,"Cohen, J.; Normile, D.",Science,2999883147,#197,
,CZI,New coronavirus threat galvanizes scientists,10.1126/science.367.6477.492,,32001631,,,2020,"Cohen, J.","Science (New York, N.Y.)",3004184096,#234,
,CZI,China virus response criticized as slow,10.1126/science.367.6478.606,,,,"As the novel coronavirus that emerged in Wuhan spreads worldwide (p. 610), China is facing criticism that its initial response was slow, and questions persist about officials' openness. People in and outside of China have praised an early warning about mysterious illnesses, sounded in a message sent 30 December 2019 by Li Wenliang, an ophthalmologist at a Wuhan hospital, to his medical school classmates. On 3 January, however, local police summoned Li, chastised him for spreading socially disruptive rumors, and made him sign a letter of self-criticism. He has since become infected and was hospitalized. Last week, the country's highest court faulted Li's detention as overreach. China is waging a fierce battle against the virus; it built a new, 1000-bed hospital in Wuhan in just 10 days, and Chinese scientists have published several papers on the virus. But in a 30 January statement leaked on social media, China's Ministry of Science and Technology urged researchers to pour their efforts into stopping its spread instead. “Until the task of prevention and control is completed, the focus should not be on the publication of papers,” the statement says As the novel coronavirus that emerged in Wuhan spreads worldwide (p. [610][1]), China is facing criticism that its initial response was slow, and questions persist about officials' openness. People in and outside of China have praised an early warning about mysterious illnesses, sounded in a message sent 30 December 2019 by Li Wenliang, an ophthalmologist at a Wuhan hospital, to his medical school classmates. On 3 January, however, local police summoned Li, chastised him for spreading socially disruptive rumors, and made him sign a letter of self-criticism. He has since become infected and was hospitalized. Last week, the country's highest court faulted Li's detention as overreach. China is waging a fierce battle against the virus; it built a new, 1000-bed hospital in Wuhan in just 10 days, and Chinese scientists have published several papers on the virus. But in a 30 January statement leaked on social media, China's Ministry of Science and Technology urged researchers to pour their efforts into stopping its spread instead. “Until the task of prevention and control is completed, the focus should not be on the publication of papers,” the statement says. > “Employees … are questioning whether they should post potentially life-saving info or check tweets first.” > > A September 2019 email by a National Weather Service official , reported by The Washington Post, after superiors rebuked forecasters for contradicting the president's inaccurate tweets about Hurricane Dorian's path. ### Agriculture The largest plague of desert locusts ( Schistocerca gregaria ) in decades is advancing across the Horn of Africa, consuming crops and threatening famine. The problem began in 2018 when unusually heavy rains on the Arabian Peninsula allowed populations to boom over several generations. In October 2019, the locusts swarmed south into Ethiopia, Eritrea, and Somalia, and in late December, they spread to Kenya, causing the worst infestation there in 70 years. Somalia—which last week declared a national emergency and asked for increased food aid—has already lost 100,000 hectares of crops and pasture. Another generation of locusts will likely hatch this month and cause more damage. The Food and Agriculture Organization of the United Nations called for $70 million to fight the outbreak with pesticides and help farmers. ### Glaciology After dropping sensors and a torpedo-shaped robot through a 700-meter hole in the ice, scientists in Antarctica last week revealed the first direct evidence that warm ocean temperatures around the rapidly retreating Thwaites Glacier could destabilize the key ice sheet. Researchers are worried because Thwaites—larger than the state of Illinois—helps block the ocean from reaching and warming the even bigger, unstable West Antarctic Ice Sheet, whose melting could eventually drive meters of sea level rise. Battling 2 months of stormy conditions, the team measured ocean waters beneath Thwaites at more than 2°C above the freezing point. The robot, Icefin (above, shown operating elsewhere in Antarctica), provided the first images of the glacier's grounding zone, the mysterious boundary where the floating coastal ice sheet attaches to bedrock. The project is part of the International Thwaites Glacier Collaboration, a multiyear effort by the United States and the United Kingdom that is wrapping up its first full field season. ### Leadership Some researchers in Colombia are calling for a little-known molecular biologist appointed as the country's first ever science minister to resign. They are outraged by reports that she treated cancer patients with a fungal extract, without running a formal clinical trial. “We can only regret that the course of how to do science in our country has been left in the hands of pseudoscience,” the Colombian Association of Medical Faculties wrote in a statement. In December 2019, Mabel Gisela Torres Torres was appointed to lead the newly created Ministry of Science, Technology and Innovation. In January, she told a newspaper she did not seek formal ethical, safety, and efficacy reviews of her work with patients because she believed the fungus posed no threat to human health. Her Ph.D. adviser has defended her and notes that metabolites in the fungi Torres studied have shown potential as a cancer treatment in cell and mouse studies. ### Environmental science ![Figure][2] CREDITS: (GRAPHIC) J. BRAINARD/ SCIENCE ; (DATA) UNITED NATIONS UNIVERSITY INSTITUTE FOR WATER, ENVIRONMENT, AND HEALTH The world's growing flows of wastewater offer a largely untapped, potentially lucrative source of energy, agricultural fertilizers, and water for irrigation, a comprehensive study says. The opportunities will increase as the annual volume of wastewater—now 380 billion cubic meters—expands by an estimated 51% by 2050, as populations and incomes multiply, says a team led by researchers at United Nations University's Institute for Water, Environment, and Health. About 13% of global demand for fertilizer could be met by recovering nitrogen, phosphorus, and potash from wastewater; such use provides a bonus, diverting nutrients from waterways, where they can create harmful eutrophication. Sewage also offers an alternative energy source. The need to plan and finance such recovery efforts is greatest in “low- and middle-income countries, where most municipal wastewater still goes into the environment untreated,” says the study, published 27 January in Natural Resources Forum. ### Conservation A decision by South Africa's government to allow breeding and genetic research on more than 30 wild species—including rhinos, lions, and cheetahs—could considerably reduce their genetic diversity, scientists warned last week. The government's action has been interpreted to allow breeders to select for commercially desirable traits, such as longer horns or larger body size; that could create genetic bottlenecks by promoting a few stud lines, the researchers wrote in the South African Journal of Science. They added that it may prove expensive or impossible to keep the intensively bred animals from mating with wild counterparts. A handful of game ranchers requested the policy, which South Africa announced in May 2019 without consulting the public or studying potential consequences. Game ranching —for hunting, meat, and tourism—already occupies more than 15% of the country, and the government wants to expand the industry. ### Funding The U.S. National Science Foundation (NSF) announced this week seven winners in its contest for “big ideas” to address societal problems. Four winning teams will receive $26,000 each to develop ideas on topics ranging from using artificial intelligence for complex problem-solving to developing small-scale technologies that sequester carbon dioxide. Three more teams earned $10,000 as runners-up. The 2026 Idea Machine contest attracted almost 800 submissions, and although some high schoolers made it to the semifinals, all the winners work at research institutions. NSF hopes to fund workshops and exploratory grants to further develop these and other ideas from contestants. ### Publishing A software company said last week it has teamed up with publishing giant Wiley to roll out in mid-2020 a tool that can signal whether findings in Wiley's scientific papers are reproducible. The software, called [Scite.ai][3], uses artificial intelligence to examine articles that cite a paper, and determines and displays whether they provide evidence supporting or contradicting the paper's findings. Users can browse and search the relevant text of the citing articles. Scite CEO Josh Nicholson says the software allows users to home in on articles that attempted to reproduce a study; of every 100 citations analyzed, Scite has found that 94 merely note the paper cited. The addition of Wiley's articles will expand Scite's current trove of more than 14 million papers from other publishers, most in the biomedical sciences. Nicholson expects his company to sign agreements with additional publishers to analyze their articles. ### Biomedicine The Chan Zuckerberg Initiative (CZI) said this week it will award $13.5 million to 30 patient advocacy groups to support their work finding treatments for rare diseases. Of an estimated 7000 rare diseases, fewer than 5% have treatments approved by the U.S. Food and Drug Administration. Each group will receive $450,000 over 2 years as well as training and mentoring as part of the foundation's Rare As One Project, launched last year to help advocates develop networks of patients, clinicians, and scientists. Most of the diseases are autoimmune, neurodegenerative, and other inherited disorders, but the list of diseases also includes rare cancers. CZI, founded by Facebook's Mark Zuckerberg and pediatrician Priscilla Chan, his wife, has made a few other awards to rare disease groups. The initiative expected to make just 10 Rare As One awards but tripled the number after receiving 275 applications. ### Conservation The Trump administration proposed last week to end penalties on owners of open oil storage ponds and other industrial operations that kill birds accidentally. The administration will instead encourage voluntary efforts to protect birds. Conservation groups cried foul, saying the change to the Migratory Bird Treaty Act of 1918 will only embolden companies to take actions that threaten vulnerable species. ### BRAIN Initiative gets leader Since its launch in 2013, the U.S. Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative has doled out about $1.3 billion to develop tools that map and manipulate the brain. Until now, the multiagency effort has had no formal director. But last week, neurobiologist John Ngai of the University of California, Berkeley, was named to take the helm in March. (A longer version of the interview is at <https://scim.ag/BRAINdirector>.) > Q: Why is BRAIN getting a director? > A:The initiative has been run day to day by a terrific team of senior program directors and staff with oversight from the 10 [U.S. National Institutes of Health (NIH)] institutes and centers that are involved in BRAIN. I think as enterprises emerge from their startup phase, the question is how do you translate this into a sustainable enterprise, and yet maintain this cutting-edge innovation? … The initiative really will benefit from somebody thinking about this 24/7. > Q: What distinguishes this second phase of BRAIN? > A:In the first phase, there was a very intentional and concentrated focus on tool development. As we learn more about how neural circuits drive behavior … we can start implementing that knowledge, in terms of treating human diseases. I am hopeful that BRAIN, with other efforts in NIH and in partnership with industry, [can create] technology platforms that could be applied across multiple disease applications. For example: a toolkit of different types of viral delivery vectors [for gene therapy] that could be applied to different parts of the brain, different cell types in the brain, and so on. > Q: What do you see as the initiative's shortcomings? > A:We have a lot of figuring out to do in terms of how to balance the unique potential of individual investigator-initiated research versus the power of large-scale projects. … [And] there is a diversity issue in terms of ethnic diversity as well as gender diversity [among applicants and funded investigators]. It's a hard problem. It just kills me that we're leaving all this talent on the table. [1]: http://www.sciencemag.org/content/367/6478/610 [2]: pending:yes [3]: https://Scite.ai",2020,"Science, American Association for the Advancement of",,2103918422,#376,
,CZI,Will novel virus go pandemic or be contained?,10.1126/science.367.6478.610,,,,"The repatriation of 565 Japanese citizens from Wuhan, China, in late January offered scientists an unexpected opportunity to learn a bit more about the novel coronavirus (2019-nCoV) raging in that city. To avoid domestic spread of the virus, Japanese officials screened every passenger for disease symptoms and tested them for the virus after they landed. Eight tested positive, but four of those had no symptoms at all, says epidemiologist Hiroshi Nishiura of Hokkaido University, Sapporo—which is a bright red flag for epidemiologists who are trying to figure out what the fast-moving epidemic has in store for humanity. If many infections go unnoticed, as the Japanese finding suggests, that vastly complicates efforts to contain the outbreak. Two months after 2019-nCoV emerged—and with well over 20,000 cases and 427 deaths as Science went to press—mathematical modelers have been racing to predict where the virus will move next, how big a toll it might ultimately take, and whether isolating patients and limiting travel will slow it. But to make confident predictions, they need to know much more about how easily the virus spreads, how sick it makes people, and whether infected people with no symptoms can still infect others. Some of that information is coming out of China. But amid the all-out battle to control the virus, and with diagnostic capabilities in short supply, Chinese researchers cannot answer all the questions. Countries with just a handful of cases, such as Japan, can also reveal important data, says Preben Aavitsland of the Norwegian Institute of Public Health. “It's up to all countries now that receive cases to collect as much information as possible.” With the limited information so far, scientists are sketching out possible paths that the virus might take, weighing the likelihoods of each, and trying to determine the fallout. “We're at this stage where defined scenarios and the evidence for and against them are really important because it allows people to plan better,” says Marc Lipsitch, an epidemiologist at the Harvard T.H. Chan School of Public Health. These scenarios break into two broad categories: The world gets the virus under control—or it doesn't. The most optimistic scenario is one in which 2019-nCoV remains mostly confined to China, where 99% of the confirmed cases have occurred so far. (By 4 February, two dozen other countries had together reported 195 cases.) “There has obviously been a huge amount of spread within China, but [elsewhere], there's no evidence of any kind of substantial human-to-human transmission,” says Robin Thompson, a mathematical epidemiologist at the University of Oxford. “The risk probably isn't as high as some models have been projecting.” If no other countries see sustained transmission and the quarantines and other measures taken in China start to reduce the number of infections there, the risk of spread might gradually go down, and the virus might eventually be quashed. This happened with the severe acute respiratory syndrome (SARS) outbreak in 2003, which ended after fewer than 9000 cases. That's what the World Health Organization (WHO), which last week declared the outbreak a Public Health Emergency of International Concern, hopes for this time. In a press conference, Director-General Tedros Adhanom Ghebreyesus called for a global version of the approach his team took in the current Ebola outbreak: Fight the disease at the source and try to keep it from gaining a foothold elsewhere. “Focus on the epicenter,” Tedros said. “If you have several epicenters, it is chaos.” Epidemiologist Marion Koopmans of Erasmus Medical Center says it may not be that hard to contain the virus in a new locale as long as the first cases are detected and isolated early—provided the virus is not highly transmissible. “We don't see it taking off in the 200 or so cases seeded outside of China,” Koopmans says. If that pattern holds, “there still is the possibility it will bend off.” She and others suspect the climate may help. Influenza typically only spreads during the winter months and hits northern and southern China at different times. If that is true for 2019-nCoV, its spread might start to slow down in the Northern Hemisphere within a few months. “That is a big question mark we're trying to assess at the moment,” says Joseph Wu, a modeler at the University of Hong Kong. But is containment realistic? Success will depend in part on whether infected people who don't have symptoms can spread the virus. Asymptomatic people are hard to find and isolate, so if they can spread disease, 2019-nCoV “will be very difficult to stop in China,” says Alessandro Vespignani, a modeler of infectious diseases at Northeastern University. But if asymptomatic transmission is rare, he says, “isolation and social distancing can have a big impact.” So far it has been difficult to get a handle on this question. Some data from China seem to support asymptomatic transmission, but none are clear-cut. A widely reported 30 January letter in The New England Journal of Medicine described the case of a Chinese businesswoman who touched off a cluster of four cases in Germany before she became sick herself. But 4 days later, it became clear the researchers had not contacted the woman, who had flown back to China, before the paper was published. In a later phone interview, she said she had experienced some symptoms while in Germany. In follow-up results announced in a 4 February press release, the researchers noted that some patients they studied shed virus even though their symptoms were mild. That's almost as bad as asymptomatic transmission, says virologist Christian Drosten of the Charité University Hospital in Berlin: Patients with mild symptoms are unlikely to seek medical care and may not even stay home, giving the virus ample opportunities to spread far and wide. Based on what they have seen so far, many researchers think it's probably too late to contain the virus. “As the virus continues to spread in China, the risk of exportation to other countries grows and sooner or later we will see it spread in another country,” Aavitsland says. So far there has been no sustained transmission outside of China, but Lipsitch expects that to change: “I would be really shocked if in 2 or 3 weeks there wasn't ongoing transmission with hundreds of cases in several countries on several continents.” If the virus does spread to all corners of the world in a pandemic, several questions will loom large: What percentage of the population will become infected, and of those, how many will get very sick or die? More severe cases place heavier demands on health care systems—hospitals in Wuhan are already overwhelmed—and result in greater fears and disruption of daily life. A deadly pandemic might force the world to make stark choices about fair access to medicines or vaccines, if they become available. It might also lead to widespread restrictions on domestic travel akin to those already in force in China, Aavitsland says. If, on the other hand, 2019-nCoV resembles the common cold or a mild flu, the spread of the virus would be less alarming. Existing travel bans likely would be lifted. Understanding the severity and case fatality rate is a challenge with any new pathogen. When a new influenza strain emerged in 2009—and went on to cause a pandemic—many worried it might turn out to be a nasty variety. It took months to establish that the new virus killed only about one in 10,000 patients. So far, mortality among known 2019-nCoV cases is about 2%, and some reports say 20% of infected people suffer severe disease. But these figures may overlook tens of thousands of people with mild disease—say, a sore throat or a low-grade fever—who never seek medical care and may not even know they were infected with 2019-nCoV. Many may have no symptoms at all. “So what looks like a horrific disease may be the horrific tip of a very large iceberg,” Lipsitch says. The fact that four Japanese evacuees were asymptomatic is a case in point. Studies in China have also reported some cases with few or no symptoms. What's missing is a large study in China, Lipsitch says. He suggests some fraction of the tests that are available in a place with many cases should be set aside for that purpose. (Current recommendations in China call for testing people with clear symptoms only.) If indeed 2019-nCoV becomes pandemic, humanity may be stuck with it indefinitely. After spreading far and wide, the virus might become endemic in the human population, just like four other coronaviruses that cause the common cold, and occasionally cause fresh outbreaks. How much death and disease it would cause is anyone's guess. The silver lining of the epidemic is that scientists have collected and shared information at record speed. “Every day that goes by we know more and every day that goes by we can do better modeling,” Vespignani says. “Unfortunately, this beast is moving very fast.”",2020,"Kupferschmidt, Kai; Cohen, Jon",Science,3005524720,#400,
,CZI,News at a glance,10.1126/science.367.6479.720,,,,"Just weeks after a novel coronavirus emerged in Wuhan, China, the outbreak continued to expand in gravity and scope. This week, the cumulative death toll surpassed 1000, compared with the more than 800 killed by another coronavirus in the 2002–03 outbreaks of severe acute respiratory syndrome (SARS). Authorities assigned official names to the virus, SARS-CoV-2, and the resulting disease, COVID-19. Li Wenliang, a 34-year-old doctor who sounded an early alarm in Wuhan about the disease only to be summoned by local police for doing so, succumbed to the virus last week.",2020,Science,Science,2755115273,#819,
,CZI,Labs scramble to spot hidden coronavirus infections | Science | AAAS,10.1126/science.367.6479.727,,,,"The seeming precision of the global tallies of cases and deaths caused by the novel coronavirus now spreading from Wuhan, China belies an alarming fact. The world is in the dark about the epidemic’s real scale and speed, because existing tests have limited powers—and testing is far too spotty. “We are underestimating how common this infection is,” cautions Jeremy Farrar, head of the Wellcome Trust. Within days of Chinese researchers releasing the sequence of the virus on 11 January, scientists developed tests capable of detecting genetic sequences that distinguish the new agent from other coronaviruses circulating in humans. By 28 January, China’s National Medical Products Administration had approved diagnostic test kits from five companies. It was an astonishing pace for the response to a pathogen never seen before—and yet it was only a beginning.",2020,"Cohen, Jon; Kupferschmidt; Kai",,3006494401,#786,
,CZI,Labs scramble to produce new coronavirus diagnostics,10.1126/science.367.6479.727,,,,"The seeming precision of the global tallies of cases and deaths caused by the novel coronavirus now spreading from Wuhan, China, belies an alarming fact. The world is in the dark about the epidemic's real scale and speed, because existing tests have limited powers—and testing is far too spotty. “We are underestimating how common this infection is,” cautions Jeremy Farrar, head of the Wellcome Trust. Within days of Chinese researchers releasing the sequence of the virus on 11 January, scientists developed tests capable of detecting genetic sequences that distinguish the new agent from other coronaviruses circulating in humans. By 28 January, China's National Medical Products Administration had approved diagnostic test kits from five companies. It was an astonishing pace for the response to a pathogen never seen before—and yet it was only a beginning",2020,"Cohen, Jon; Kupferschmidt, Kai",Science,3006494401,#821,
,CZI,The health carer,10.1126/science.367.6479.730,,,,"On 2 January 2019, Tedros Adhanom Ghebreyesus faced a life-or-death decision. The director-general of the World Health Organization (WHO) had spent New Year's Eve in Bunia, Democratic Republic of the Congo (DRC), to boost the morale of staff fighting the second biggest Ebola epidemic ever. As he was getting ready to board a helicopter to Uganda, where he was scheduled to meet Prime Minister Ruhakana Rugunda, Tedros had to decide whether to bring along a young Congolese man named Charles Lwanga-Kikwaya. The day before, a group of Ebola vaccinators was attacked by a group of young men and women—one of many assaults WHO staff has had to endure—and Lwanga-Kikwaya had been hit on the head with a large stone. His injury was serious, says Jeremy Farrar, head of the Wellcome Trust, who accompanied Tedros and examined the patient. “We quickly decided we either had to evacuate him or he was going to die,” says Farrar, who trained as a neurologist.",2020,"Kupferschmidt, Kai",Science,3006481984,#820,
,CZI,Strategies shift as coronavirus pandemic looms,10.1126/science.367.6481.962,,,,"The virus may be spreading stealthily in many more places. A modeling group at Imperial College London has estimated that about two-thirds of the cases exported from China have yet to be detected. As Science went to press, the World Health Organization (WHO) still avoided using the word “pandemic” to describe the burgeoning crisis, instead talking about “epidemics in different parts of the world.” But many scientists say that regardless of what it's called, the window for containment is now almost certainly shut. “It looks to me like this virus really has escaped from China and is being transmitted quite widely,” says Christopher Dye, an epidemiologist at the University of Oxford. “I'm now feeling much more pessimistic that it can be controlled.” In the United States, “disruption to everyday life might be severe,” Nancy Messonnier, who leads the coronavirus response for the U.S. Centers for Disease Control and Prevention, warned on 25 February. “We are asking the American public to work with us to prepare for the expectation that this is going to be bad.”",2020,"Cohen, Jon; Kupferschmidt, Kai",Science,3006494401,#2658,
,CZI,Preprints bring ‘firehose’ of outbreak data,10.1126/science.367.6481.963,,,,"The Wu-han Clan is just one example of how the COVID-19 outbreak is transforming how scientists communicate about fast-moving health crises. A torrent of data is being released daily by preprint servers that didn't even exist a decade ago, then dissected on platforms such as Slack and Twitter, and in the media, before formal peer review begins. Journal staffers are working overtime to get manuscripts reviewed, edited, and published at record speeds. The venerable New England Journal of Medicine (NEJM) posted one COVID-19 paper within 48 hours of submission. Viral genomes posted on a platform named GISAID, more than 200 so far, are analyzed instantaneously by a phalanx of evolutionary biologists who share their phylogenetic trees in preprints and on social media.",2020,"Kupferschmidt, Kai",Science,,#2611,
,CZI,Can China's COVID-19 strategy work elsewhere?,10.1126/science.367.6482.1061,,32139521,,,2020,"Kupferschmidt, K.; Cohen, J.","Science (New York, N.Y.)",3005550222,#4786,
,CZI,The effect of travel restrictions on the spread of the 2019 novel coronavirus (COVID-19) outbreak,10.1126/science.aba9757,,32144116,,"Motivated by the rapid spread of COVID-19 in Mainland China, we use a global metapopulation disease transmission model to project the impact of travel limitations on the national and international spread of the epidemic. The model is calibrated based on internationally reported cases, and shows that at the start of the travel ban from Wuhan on 23 January 2020, most Chinese cities had already received many infected travelers. The travel quarantine of Wuhan delayed the overall epidemic progression by only 3 to 5 days in Mainland China, but has a more marked effect at the international scale, where case importations were reduced by nearly 80% until mid February. Modeling results also indicate that sustained 90% travel restrictions to and from Mainland China only modestly affect the epidemic trajectory unless combined with a 50% or higher reduction of transmission in the community.",2020,"Chinazzi, M.; Davis, J. T.; Ajelli, M.; Gioannini, C.; Litvinova, M.; Merler, S.; Pastore, Y. Piontti A.; Mu, K.; Rossi, L.; Sun, K.; Viboud, C.; Xiong, X.; Yu, H.; Halloran, M. E.; Longini, I. M., Jr.; Vespignani, A.","Science (New York, N.Y.)",3006078464,#5137,
,CZI,Can an anti-HIV combination or other existing drugs outwit the new coronavirus?,10.1126/science.abb0659,,,,,2020,"Cohen, Jon",Science,3003329639,#242,
,CZI,Scientists are racing to model the next moves of a coronavirus that's still hard to predict | Science | AAAS,10.1126/science.abb2161,,,,"Beyond China itself, Thailand is the country that most likely will have people who arrive at one of its airports with an infection by the novel coronavirus (2019-nCoV) that has sickened more than 30,000 people. So says the latest update of a global risk assessment model created by a team of researchers from the Humboldt University of Berlin and the Robert Koch Institute that relies on air travel data.",2020,"Cohen, Jon",,3005441092,#553,
,CZI,Mission impossible? WHO director fights to prevent a pandemic without offending China | Science | AAAS,10.1126/science.abb2477,,,,"New outbreak comes as Tedros Adhanom Ghebreyesus struggles to raise more money, thwart Ebola, and fight health misinformation",2020,"Kupferschmidt, Kai",Science,3005563651,#609,
,CZI,Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation,10.1126/science.abb2507,,32075877,,"The outbreak of a novel betacoronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure (MCM) development, we determined a 3.5 Å-resolution cryo-EM structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also show biophysical and structural evidence that the 2019-nCoV S binds ACE2 with higher affinity than SARS-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable rapid development and evaluation of MCMs to address the ongoing public health crisis.",2020,"Wrapp, Daniel; Wang, Nianshuang; Corbett, Kizzmekia S.; Goldsmith, Jory A.; Hsieh, Ching-Lin; Abiona, Olubukola; Graham, Barney S.; McLellan, Jason S.",Science,3005605085,#1461,
,CZI,Labs scramble to spot hidden coronavirus infections,10.1126/science.abb2651,,,,"The seeming precision of the global tallies of cases and deaths caused by the novel coronavirus now spreading from Wuhan, China belies an alarming fact. ... (A study group of the International Committee on Taxonomy of Viruses christened the novel virus severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, the same day). But many news stories have reported shortages of diagnostics in Hubei.",2020,"Jon Cohen, et al.",Science,3006483726,#663,
,CZI,Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2,10.1126/science.abb2762,,32132184,,"Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious epidemic COVID-19. Here we present cryo-EM structures of full-length human ACE2, in the presence of a neutral amino acid transporter B(0)AT1, with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 A, with a local resolution of 3.5 A at the ACE2-RBD interface. The ACE2-B(0)AT1 complex is assembled as a dimer of heterodimers, with the Collectrin-like domain (CLD) of ACE2 mediating homo-dimerization. The RBD is recognized by the extracellular peptidase domain (PD) of ACE2 mainly through polar residues. These findings provide important insights to the molecular basis for coronavirus recognition and infection.",2020,"Yan, R.; Zhang, Y.; Li, Y.; Xia, L.; Guo, Y.; Zhou, Q.","Science (New York, N.Y.)",2164706157,#5357,
,CZI,The costs of secrecy,10.1126/science.abb4420,,,,"""Without freedom of speech there is no modern world, just a barbaric one.” These words from China's most famous artist and activist, Ai Weiwei, have never been more important. Ai Weiwei would probably agree that China's actions in the coronavirus crisis require the voice of the scientific community, and he wouldn't be surprised that getting folks to say something has been a challenge. I didn't want to be the person to write this editorial. I felt that it would best come from someone inside China with a direct connection to the situation. Such a person could help dispel or reinforce the scraps of information coming from the intrepid journalists and the few courageous eyewitnesses. But over the past few weeks, I've been discouraged by the responses of such individuals who declined or didn't respond to an invitation to write a forthcoming editorial about China's secrecy on coronavirus. Some of these scientists and experts even expressed doubt that I'd find such a gutsy author at any organization in China to write such a piece.",2020,"Thorp, H. Holden",Science,245508297,#2531,
,CZI,China’s aggressive measures have slowed the coronavirus. They may not work in other countries,10.1126/science.abb5426,,,,"The question now is whether the world can take lessons from China’s apparent success—and whether the massive lockdowns and electronic surveillance measures imposed by an authoritarian government would work in other countries. “When you spend 20, 30 years in this business it’s like, ‘Seriously, you’re going to try and change that with those tactics?’” says Bruce Aylward, a Canadian WHO epidemiologist who led the international team and briefed journalists about its findings in Beijing and Geneva last week. “Hundreds of thousands of people in China did not get COVID-19 because of this aggressive response.”",2020,"Cohen, Kai Kupferschmidt; Jon",Science,,#3193,
,CZI,"Dog noses detect heat, the world faces coronavirus, and scientists search for extraterrestrial life",10.1126/science.abb5429,,,,"On this week’s show, Online News Editor David Grimm joins host Sarah Crespi to discuss how dogs’ cold noses may be able to sense warm bodies. Read the research. International News Editor Martin Enserink shares the latest from our reporters covering coronavirus. And finally, from a recording made at this year’s AAAS annual meeting, host Meagan Cantwell talks with Jill Tarter, chair emeritus at the SETI Institute, about the newest technologies being used to search for alien life, what a positive signal would look like, and how to inform the public if extraterrestrial life ever were detected. This week’s episode was produced with help from Podigy.",2020,"Crespi, Sarah",Science,2138505189,#5162,
,CZI,Indonesia finally reports two coronavirus cases. Scientists worry it has many more,10.1126/science.abb5653,,,,"Indonesia finally reported its first two COVID-19 cases on Monday. At a press conference in Jakarta, President Joko Widodo announced that two women aged 31 and 64 from Depok had contracted the virus. But some scientists believe the country, which has close ties to China, almost certainly has a “silent epidemic” within its borders and should urgently boost its surveillance efforts. Scientists at the Eijkman Institute for Molecular Biology tell Science they have offered to the Indonesian Ministry of Health to help test more people, but have been snubbed so far. The detection of the first two cases, along with measures to prevent the spread of the disease, demonstrate Indonesia’s seriousness and capability to deal with the COVID-19 epidemic, Widodo said yesterday. “Since the beginning, we have been serious in strictly following WHO [World Health Organization] guidelines regarding the coronavirus issue,” he said.",2020,"Rochmyaningsih, Dyna",Science,1990285966,#4995,
,CZI,‘We had to act.’ How coronavirus fears forced physics society to nix giant meeting,10.1126/science.abb5683,,,,"Harold Dorwin/Center for Astrophysics/Harvard & Smithsonian The March Meeting of the American Physical Society (APS) wasn’t the first event canceled for fear of the coronavirus, but it was nixed in dramatic fashion.",2020,"Cho, Adrian",Sccience,,#3627,
,CZI,"With $115 million, more than 80 Boston researchers will collaborate to tackle COVID-19",10.1126/science.abb6021,,,,"A $115 million collaboration to tackle the rapidly spreading viral disease COVID-19, led by heavy hitters of Boston science and funded by a Chinese property development company, kicked off today as the group’s leaders pledged to take on the virus on many fronts. The project brings together researchers at many of the city’s top academic institutions, along with local biotechnology companies such as Moderna. Those leading it hope they can quickly funnel money into studies that will build off a new repository of samples from infected people and community surveillance, materials that can be rapidly shared among scientists. The project, they anticipate, should answer critical questions about how COVID-19 is spreading and how best to prevent and treat infections.",2020,"Couzin-Frankel, Jennifer",Science,2161064841,#4594,
,CZI,Why airport screening won’t stop the spread of coronavirus,10.1126/science.abb6136,,,,"If you have traveled internationally the past 2 months, you may have encountered them: health officers briefly pointing a thermometer gun at your forehead or watching as you go by to check for signs of a cough or difficulty breathing. Many countries are now watching arriving and departing air passengers who might suffer from the viral disease COVID-19; some require passengers to fill out health declarations. (Some also simply ban or quarantine those who have recently been in outbreak hot spots.) Exit and entry screening may look reassuring, but experience with other diseases shows it’s exceedingly rare for screeners to detect infected passengers. Just last week, eight passengers who later tested positive for COVID-19 arrived in Shanghai from Italy and passed the airport screeners unnoticed, for example. And even if screeners do find the occasional case, it has almost no impact on the course of an outbreak.",2020,"Normile, Dennis",Science,,#4929,
,CZI,"Quarantined at home now, U.S. scientist describes his visit to China’s hot zone",10.1126/science.abb6154,,,,"On 13 February, Clifford Lane went to a Washington, D.C.–area airport to catch a flight to Japan, where he would help launch a study of an experimental drug, remdesivir, against coronavirus disease 2019 (COVID-19). Lane is a deputy director at the U.S. National Institute of Allergy and Infectious Diseases and a right-hand man to Anthony Fauci, head of NIAID and the top research scientist in the country advising the White House on the outbreak of the virus. As Lane waited to board his plane, he was told that his final destination had changed. “I get an email, ‘You need to go to China.’ It’s like, are you kidding?” Lane had been selected as one of two U.S. scientists to join a World Health Organization team of 13 international researchers who would tour five different cities with 12 Chinese colleagues to get a firsthand look at the coronavirus epidemic there. The joint mission, which ran from 16–23 February led to a report that offered more details about the clinical course of COVID-19 and the epidemiology in China than had appeared anywhere before.",2020,"Cohen, Jon",Science,,#5151,
,CZI,Coronavirus disruptions could hurt North Korea’s efforts to treat tuberculosis,10.1126/science.abb6184,,,,"North Korea watchers warn that the country’s aggressive measures to defend itself against COVID-19, the illness caused by the novel coronavirus, are hobbling efforts to combat tuberculosis (TB) and other infectious diseases. Sandwiched between two COVID-19 hot spots—China and South Korea—North Korea at the end of January suspended international flights and severed its rail link with China. Since then, cargo containers headed to North Korea’s port in Nampo have stalled in Dalian, China, snagged on red tape in China and new quarantine procedures in Nampo. The only way in and out of North Korea now is a road crossing on its northern border with China. North Korea’s state media has said the border restrictions will remain in effect until COVID-19 has stopped spreading or a vaccine is available. That puts North Korea’s thousands of TB patients in a precarious situation. Three containers with first-line TB drugs are among hundreds held up in Dalian, says a U.S.-based humanitarian organization official, who requested anonymity. The official notes that North Korea’s supply of first-line TB drugs is expected to run out in May or June. The situation is even more perilous for North Koreans infected with multidrug-resistant TB strains. Treatment lapses can lead to even more recalcitrant strains. “Truly it opens grave concern” about the development of extensively drug-resistant TB in North Korea, the official says. Related",2020,"Stone, Richard",Science,,#5245,
,CZI,"Top stories: Bungled coronavirus testing, disarming ‘atomic bomb’ cells, and jet stream blocking",10.1126/science.abb6188,,,,"Speed is critical in the response to COVID-19. So why has the United States been so slow in its attempt to develop reliable diagnostic tests and use them widely? One answer is that a test kit designed by the U.S. Centers for Disease Control and Prevention (CDC) and rolled out to state and local labs late last month contained a faulty reagent. The problems have led many to doubt the accuracy of confirmed tallies of the disease. But the situation may soon improve, as the Food and Drug Administration comes up with a workaround for the faulty CDC kit.",2020,"Pérez Ortega, Rodrigo",Science,,#4962,
,CZI,Maybe not an overreaction,10.1126/scitranslmed.aba9019,,,,"A mathematical simulation of coronavirus COVID-19 estimated the number of infections to be far worse than reported. Starting in December 2019, a novel coronavirus, known as COVID-19, caused growing cases of atypical pneumonia in the city of Wuhan, China. The virus spread. As of 12 February 2020, a total of 45,204 confirmed cases had been reported from China and 519 confirmed cases from 27 countries worldwide. Among the reported victims, 1116 died. When facing an epidemic as such, a dangerous mistake that countries over the world can make is to rely entirely on confirmed data but underestimate the actual size of infections. Causes of underestimation include the limitation of resources, as there can be insufficient quarantine spaces, detection reagents, and medical personnel to identify infections in real time. Additionally, the lack of symptoms from the virus in its dormant state can delay confirmation. There is also a fear of data being manipulated or downplayed by officials due to economic and political concerns.",2020,"Han, Li-Hsin",,3005971507,#772,
,CZI,Antiviral Theatrics?,10.1126/scitranslmed.abb2600,,,,"This, though, is an official organ of the Chinese state – none more so – showing all sorts of white-fog-spraying devices being deployed outdoors, with the caption “Full-front disinfection work has started in #Wuhan, an effort to contain the spread of #coronavirus“. ... Maybe there’s something in the mix that someone thinks will do some good against coronavirus particles – I doubt if they’re correct, if so – or maybe the whole thing is just meant to show that the Authorities Are Doing Something.",2020,"Lowe, Derek",Science,2995332254,#698,
,CZI,Negative Nasopharyngeal and Oropharyngeal Swab Does Not Rule Out COVID-19,10.1128/jcm.00297-20,,32102856,,"Coronavirus Disease 19 (COVID-19), has become the Public Health Emergency of International Concern.....",2020,"Winichakoon, P.; Chaiwarith, R.; Liwsrisakun, C.; Salee, P.; Goonna, A.; Limsukon, A.; Kaewpoowat, Q.",Journal of clinical microbiology,2134211166,#2974,
,CZI,"Improved molecular diagnosis of COVID-19 by the novel, highly sensitive and specific COVID-19-RdRp/Hel real-time reverse transcription-polymerase chain reaction assay validated in vitro and with clinical specimens",10.1128/jcm.00310-20,,32132196,,"On 31st December 2019, the World Health Organization was informed of a cluster of cases of pneumonia of unknown etiology in Wuhan, China. Subsequent investigations identified a novel coronavirus, now named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from the affected patients. Highly sensitive and specific laboratory diagnostics are important for controlling the rapidly evolving SARS-CoV-2-associated Coronavirus Disease 2019 (COVID-19) epidemic. In this study, we developed and compared the performance of three novel real-time RT-PCR assays targeting the RNA-dependent RNA polymerase (RdRp)/helicase (Hel), spike (S), and nucleocapsid (N) genes of SARS-CoV-2 with that of the reported RdRp-P2 assay which is used in >30 European laboratories. Among the three novel assays, the COVID-19-RdRp/Hel assay had the lowest limit of detection in vitro (1.8 TCID50/ml with genomic RNA and 11.2 RNA copies/reaction with in vitro RNA transcripts). Among 273 specimens from 15 patients with laboratory-confirmed COVID-19 in Hong Kong, 77 (28.2%) were positive by both the COVID-19-RdRp/Hel and RdRp-P2 assays. The COVID-19-RdRp/Hel assay was positive for an additional 42 RdRd-P2-negative specimens [119/273 (43.6%) vs 77/273 (28.2%), P<0.001], including 29/120 (24.2%) respiratory tract specimens and 13/153 (8.5%) non-respiratory tract specimens. The mean viral load of these specimens was 3.21*104 RNA copies/ml (range, 2.21*102 to 4.71*105 RNA copies/ml). The COVID-19-RdRp/Hel assay did not cross-react with other human-pathogenic coronaviruses and respiratory pathogens in cell culture and clinical specimens, whereas the RdRp-P2 assay cross-reacted with SARS-CoV in cell culture. The highly sensitive and specific COVID-19-RdRp/Hel assay may help to improve the laboratory diagnosis of COVID-19.",2020,"Chan, Jasper Fuk-Woo; Yip, Cyril Chik-Yan; To, Kelvin Kai-Wang; Tang, Tommy Hing-Cheung; Wong, Sally Cheuk-Ying; Leung, Kit-Hang; Fung, Agnes Yim-Fong; Ng, Anthony Chin-Ki; Zou, Zijiao; Tsoi, Hoi-Wah; Choi, Garnet Kwan-Yue; Tam, Anthony Raymond; Cheng, Vincent Chi-Chung; Chan, Kwok-Hung; Tsang, Owen Tak-Yin; Yuen, Kwok-Yung",Journal of clinical microbiology,2575652810,#5099,
,CZI,Suggestions casted to the novel coronavirus nucleic acid amplification test from viral pneumonia pathogenesis,10.1128/JCM.00490-15,,,,"An outbreak of Novel Coronavirus (2019-nCoV), results in Coronavirus disease that began in Wuhan, China, has spread rapidly with cases now confirmed in multiple countries. Nucleic acid amplification test (NAAT), represent by reverse-transcriptase polymerase chain reaction (RT-PCR) plays an important role in disease diagnosis and treatment evaluation. The test results by RT-PCR have attracted much attention recently. As understanding to this novel pathogen is still limited, it would be much help to combine the knowledge about its pathogenesis to judge the test results, in addition to review the quality control in laboratory. This review will focus on understanding the specific RT-PCR performance of the 2019-nCoV, under the background of viral pneumonia. The purpose of this review is to add value to NAAT of 2019-nCoV, with combined knowledge of epidemiology, pathogenesis, clinical characteristics and pre-analysis quality control from viral pneumonia.",2020,"ZHAO, Xiuying",Chinese Journal of Laboratory Medicine,1829288473,#2052,
,CZI,Analysis of false-negative results for 2019 novel coronavirus nucleic acid test and related countermeasures,10.1128/JCM.00490-15,,,,"In December 2019, a cluster of patients with pneumonia of unknown cause were linked to a seafood wholesale market in Wuhan, China. Some studies found that the virus was a new kind of virus which had never been found in the human body. Then, the virus was named 2019 Novel Coronavirus (2019-nCoV) by the World Health Organization (WHO). 2019-nCoV nucleic acid detection is one of the essential indicators of NCP (Novel Coronavirus Pneumonia). Recently, some false-negative cases in China-Japan Friendship Hospital and Hangzhou Hospital led the clinical doctors to question the value of the nucleic acid detection. In this paper, more than 3 000 results of 2019-nCoV detection in Zhongnan Hospital, Wuhan University were analyzed. Attention should be paid to the root cause of false-negative results and the related countermeasures should be taken.",2020,"LI, Jin; YE, Guangming; CHEN, Liangjun; WANG, Jiajun; LI, Yirong",Chinese Journal of Laboratory Medicine,1829288473,#2209,
,CZI,Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS,10.1128/JVI.00127-20,,,,"Recently a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by SARS coronavirus (SARS-CoV). Since SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. Here we analyzed the potential receptor usage by 2019-nCoV, based on the rich knowledge about SARS-CoV and the newly released sequence of 2019-nCoV. First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. Second, several critical residues in 2019-nCoV RBM (particularly Gln493) provide favorable interactions with human ACE2, consistent with 2019-nCoV&#039;s capacity for human cell infection. Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV, and may help epidemic surveillance and preventive measures against 2019-nCoV.SignificanceThe recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002-2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.",2020,"Wan, Yushun; Shang, Jian; Graham, Rachel; Baric, Ralph S.; Li, Fang",Journal of Virology,3004348779,#46,
,CZI,Molecular Basis of Binding between Middle East Respiratory Syndrome Coronavirus and CD26 from Seven Bat Species,10.1128/JVI.01387-19,,,,"Continued reports of Middle East respiratory syndrome coronavirus (MERS-CoV) infecting humans have occurred since the identification of this virus in 2012. MERS-CoV is prone to cause endemic disease in the Middle East, with several dozen spillover infections to other continents. It is hypothesized that MERS-CoV originated from bat coronaviruses and that dromedary camels are its natural reservoir. Although gene segments identical to MERS-CoV were sequenced from certain species of bats and one species experimentally shed the virus, it is still unknown whether other bats can transmit the virus. Here, at the molecular level, we found that all purified bat CD26s (bCD26s) from a diverse range of species interact with the receptor binding domain (RBD) of MERS-CoV, with equilibrium dissociation constant values ranging from several to hundreds at the micromolar level. Moreover, all bCD26s expressed in this study mediated the entry of pseudotyped MERS-CoV to receptor-expressing cells, indicating the broad potential engagement of bCD26s as MERS-CoV receptors. Further structural analysis indicated that in the bat receptor, compared to the human receptor, substitutions of key residues and their adjacent amino acids leads to decreased binding affinity to the MERS-RBD. These results add more evidence to the existing belief that bats are the original source of MERS-CoV and suggest that bCD26s in many species can mediate the entry of the virus, which has significant implications for the surveillance and control of MERS-CoV infection.IMPORTANCE In this study, we found that bat CD26s (bCD26s) from different species exhibit large diversities, especially in the region responsible for binding to the receptor binding domain (RBD) of Middle East respiratory syndrome coronavirus (MERS-CoV). However, they maintain the interaction with MERS-RBD at varied affinities and support the entry of pseudotyped MERS-CoV. These bat receptors polymorphisms seem to confer evolutionary pressure for the adaptation of CD26-binding virus, such as the ancestor of MERS-CoV, and led to the generation of diversified CD26-engaging CoV strains. Thus, our data add more evidence to support that bats are the reservoir of MERS-CoV and similar viruses, as well as further emphasize the necessity to survey MERS-CoV and other CoVs among bats.",2020,"Yuan, Yuan; Qi, Jianxun; Peng, Ruchao; Li, Chunrui; Lu, Guangwen; Yan, Jinghua; Wang, Qihui; Gao, George Fu",Journal of Virology,2991340753,#2071,
,CZI,Molecular Basis of Binding between Middle East Respiratory Syndrome Coronavirus and CD26 from Seven Bat Species Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection,10.1128/jvi.01387-19 10.1128/mBio.02764-19,,,,"Continued reports of Middle East respiratory syndrome coronavirus (MERS-CoV) infecting humans have occurred since the identification of this virus in 2012. MERS-CoV is prone to cause endemic disease in the Middle East, with several dozen spillover infections to other continents. It is hypothesized that MERS-CoV originated from bat coronaviruses and that dromedary camels are its natural reservoir. Although gene segments identical to MERS-CoV were sequenced from certain species of bats and one species experimentally shed the virus, it is still unknown whether other bats can transmit the virus. Here, at the molecular level, we found that all purified bat CD26s (bCD26s) from a diverse range of species interact with the receptor binding domain (RBD) of MERS-CoV, with equilibrium dissociation constant values ranging from several to hundreds at the micromolar level. Moreover, all bCD26s expressed in this study mediated the entry of pseudotyped MERS-CoV to receptor-expressing cells, indicating the broad potential engagement of bCD26s as MERS-CoV receptors. Further structural analysis indicated that in the bat receptor, compared to the human receptor, substitutions of key residues and their adjacent amino acids leads to decreased binding affinity to the MERS-RBD. These results add more evidence to the existing belief that bats are the original source of MERS-CoV and suggest that bCD26s in many species can mediate the entry of the virus, which has significant implications for the surveillance and control of MERS-CoV infection.IMPORTANCE In this study, we found that bat CD26s (bCD26s) from different species exhibit large diversities, especially in the region responsible for binding to the receptor binding domain (RBD) of Middle East respiratory syndrome coronavirus (MERS-CoV). However, they maintain the interaction with MERS-RBD at varied affinities and support the entry of pseudotyped MERS-CoV. These bat receptors polymorphisms seem to confer evolutionary pressure for the adaptation of CD26-binding virus, such as the ancestor of MERS-CoV, and led to the generation of diversified CD26-engaging CoV strains. Thus, our data add more evidence to support that bats are the reservoir of MERS-CoV and similar viruses, as well as further emphasize the necessity to survey MERS-CoV and other CoVs among bats. Coronaviruses (CoVs) are common human and animal pathogens that can transmit zoonotically and cause severe respiratory disease syndromes. CoV infection requires spike proteins, which bind viruses to host cell receptors and catalyze virus-cell membrane fusion. Several CoV strains have spike proteins with two receptor-binding domains, an S1A that engages host sialic acids and an S1B that recognizes host transmembrane proteins. As this bivalent binding may enable broad zoonotic CoV infection, we aimed to identify roles for each receptor in distinct infection stages. Focusing on two betacoronaviruses, murine JHM-CoV and human Middle East respiratory syndrome coronavirus (MERS-CoV), we found that virus particle binding to cells was mediated by sialic acids; however, the transmembrane protein receptors were required for a subsequent virus infection. These results favored a two-step process in which viruses first adhere to sialic acids and then require subsequent engagement with protein receptors during infectious cell entry. However, sialic acids sufficiently facilitated the later stages of virus spread through cell-cell membrane fusion, without requiring protein receptors. This virus spread in the absence of the prototype protein receptors was increased by adaptive S1A mutations. Overall, these findings reveal roles for sialic acids in virus-cell binding, viral spike protein-directed cell-cell fusion, and resultant spread of CoV infections.IMPORTANCE CoVs can transmit from animals to humans to cause serious disease. This zoonotic transmission uses spike proteins, which bind CoVs to cells with two receptor-binding domains. Here, we identified the roles for the two binding processes in the CoV infection process. Binding to sialic acids promoted infection and also supported the intercellular expansion of CoV infections through syncytial development. Adaptive mutations in the sialic acid-binding spike domains increased the intercellular expansion process. These findings raise the possibility that the lectin-like properties of many CoVs contribute to facile zoonotic transmission and intercellular spread within infected organisms.",2020,"Yuan, Yuan; Qi, Jianxun; Peng, Ruchao; Li, Chunrui; Lu, Guangwen; Yan, Jinghua; Wang, Qihui; Gao, George Fu; Qing, Enya; Hantak, Michael; Perlman, Stanley; Gallagher, Tom",Journal of Virology,2991340753,#2070,
,CZI,Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection,10.1128/JVI.01774-19,,,,"Traditionally, the emergence of coronaviruses (CoVs) has been attributed to a gain in receptor binding in a new host. Our previous work with severe acute respiratory syndrome (SARS)-like viruses argued that bats already harbor CoVs with the ability to infect humans without adaptation. These results suggested that additional barriers limit the emergence of zoonotic CoV. In this work, we describe overcoming host restriction of two Middle East respiratory syndrome (MERS)-like bat CoVs using exogenous protease treatment. We found that the spike protein of PDF2180-CoV, a MERS-like virus found in a Ugandan bat, could mediate infection of Vero and human cells in the presence of exogenous trypsin. We subsequently show that the bat virus spike can mediate the infection of human gut cells but is unable to infect human lung cells. Using receptor-blocking antibodies, we show that infection with the PDF2180 spike does not require MERS-CoV receptor DPP4 and antibodies developed against the MERS spike receptor-binding domain and S2 portion are ineffective in neutralizing the PDF2180 chimera. Finally, we found that the addition of exogenous trypsin also rescues HKU5-CoV, a second bat group 2c CoV. Together, these results indicate that proteolytic cleavage of the spike, not receptor binding, is the primary infection barrier for these two group 2c CoVs. Coupled with receptor binding, proteolytic activation offers a new parameter to evaluate the emergence potential of bat CoVs and offers a means to recover previously unrecoverable zoonotic CoV strains.IMPORTANCE Overall, our studies demonstrate that proteolytic cleavage is the primary barrier to infection for a subset of zoonotic coronaviruses. Moving forward, the results argue that both receptor binding and proteolytic cleavage of the spike are critical factors that must be considered for evaluating the emergence potential and risk posed by zoonotic coronaviruses. In addition, the findings also offer a novel means to recover previously uncultivable zoonotic coronavirus strains and argue that other tissues, including the digestive tract, could be a site for future coronavirus emergence events in humans.",2020,"Menachery, Vineet D.; Dinnon, Kenneth H.; Yount, Boyd L.; McAnarney, Eileen T.; Gralinski, Lisa E.; Hale, Andrew; Graham, Rachel L.; Scobey, Trevor; Anthony, Simon J.; Wang, Lingshu; Graham, Barney; Randell, Scott H.; Lipkin, W. Ian; Baric, Ralph S.",Journal of Virology,2994156659,#2167,
,CZI,Nucleocapsid Protein Recruitment to Replication-Transcription Complexes Plays a Crucial Role in Coronaviral Life Cycle,10.1128/JVI.01925-19,,,,"Coronavirus (CoV) nucleocapsid (N) proteins are key for incorporating genomic RNA into progeny viral particles. In infected cells, N proteins are present at the replication-transcription complexes (RTCs), the sites of CoV RNA synthesis. It has been shown that N proteins are important for viral replication and that the one of mouse hepatitis virus (MHV), a commonly used model CoV, interacts with nonstructural protein 3 (nsp3), a component of the RTCs. These two aspects of the CoV life cycle, however, have not been linked. We found that the MHV N protein binds exclusively to nsp3 and not other RTC components by using a systematic yeast two-hybrid approach, and we identified two distinct regions in the N protein that redundantly mediate this interaction. A selective N protein variant carrying point mutations in these two regions fails to bind nsp3 in vitro, resulting in inhibition of its recruitment to RTCs in vivo. Furthermore, in contrast to the wild-type N protein, this N protein variant impairs the stimulation of genomic RNA and viral mRNA transcription in vivo and in vitro, which in turn leads to impairment of MHV replication and progeny production. Altogether, our results show that N protein recruitment to RTCs, via binding to nsp3, is an essential step in the CoV life cycle because it is critical for optimal viral RNA synthesis.IMPORTANCE CoVs have long been regarded as relatively harmless pathogens for humans. Severe respiratory tract infection outbreaks caused by severe acute respiratory syndrome CoV and Middle East respiratory syndrome CoV, however, have caused high pathogenicity and mortality rates in humans. These outbreaks highlighted the relevance of being able to control CoV infections. We used a model CoV, MHV, to investigate the importance of the recruitment of N protein, a central component of CoV virions, to intracellular platforms where CoVs replicate, transcribe, and translate their genomes. By identifying the principal binding partner at these intracellular platforms and generating a specific mutant, we found that N protein recruitment to these locations is crucial for promoting viral RNA synthesis. Moreover, blocking this recruitment strongly inhibits viral infection. Thus, our results explain an important aspect of the CoV life cycle and reveal an interaction of viral proteins that could be targeted in antiviral therapies.",2020,"Cong, Yingying; Ulasli, Mustafa; Schepers, Hein; Mauthe, Mario; V’kovski, Philip; Kriegenburg, Franziska; Thiel, Volker; de Haan, Cornelis A. M.; Reggiori, Fulvio",Journal of Virology,2989769422,#2317,
,CZI,Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry,10.1128/JVI.02015-19,,,,"Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral entry into cells by first binding to a receptor on the host cell surface and then fusing viral and host membranes. In this study, we investigated how a neutralizing monoclonal antibody (MAb), which targets the receptor-binding domain (RBD) of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays. Our results showed that MAb binds to the virus surface spike, allowing it to undergo conformational changes and become prone to proteolytic activation. Meanwhile, MAb binds to cell surface IgG Fc receptor, guiding viral entry through canonical viral-receptor-dependent pathways. Our data suggest that the antibody/Fc-receptor complex functionally mimics viral receptor in mediating viral entry. Moreover, we characterized MAb dosages in viral-receptor-dependent, Fc-receptor-dependent, and both-receptors-dependent viral entry pathways, delineating guidelines on MAb usages in treating viral infections. Our study reveals a novel molecular mechanism for antibody-enhanced viral entry and can guide future vaccination and antiviral strategies.IMPORTANCE Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy.",2020,"Wan, Yushun; Shang, Jian; Sun, Shihui; Tai, Wanbo; Chen, Jing; Geng, Qibin; He, Lei; Chen, Yuehong; Wu, Jianming; Shi, Zhengli; Zhou, Yusen; Du, Lanying; Li, Fang",Journal of Virology,2995449088,#10,
,CZI,Strategies against the novel coronavirus: Possible applications of the experimental Ebola drug remdesivir are being tested,10.1128/JVI.03050-13,,,,,2020,,Deutsche Apotheker Zeitung,1967666468,#2472,
,CZI,Emergency response plan for the neonatal intensive care unit during epidemic of 2019 novel coronavirus,10.1136/archdischild-2018-316336,,32051072,,"2019 novel coronavirus (2019-nCoV) infection has been spreading in China since December 2019. Neonates are presumably the high-risk population susceptible to 2019-nCoV due to immature immune function. The neonatal intensive care unit (NICU) should be prepared for 2019-nCoV infections as far as possible. The emergency response plan enables the efficient response capability of NICU. During the epidemic of 2019-nCoV, the emergency response plan for the NICU should be based on the actual situation, including diagnosis, isolation, and treatment, as well as available equipment and staffing, and take into account the psychosocial needs of the families and neonatal care staff.",2020,"Pediatric Committee, Medical Association of Chinese People′s Liberation Army; Editorial Committee of Chinese Journal of Contemporary, Pediatrics",Zhongguo Dang Dai Er Ke Za Zhi,2917076901,#812,
,CZI,Novel Coronavirus disease 2019 (COVID-19): The importance of recognising possible early ocular manifestation and using protective eyewear,10.1136/bjophthalmol-2020-315994,,32086236,,,2020,"Li, Ji-Peng Olivia; Lam, Dennis Shun Chiu; Chen, Youxin; Ting, Daniel Shu Wei",Br J Ophthalmol,3006602665,#1591,
,CZI,China coronavirus: cases surge as official admits human to human transmission,10.1136/bmj.m236,,,,,2020,"Parry, J.",BMJ (Clinical research ed.),3000039309,#152,
,CZI,China coronavirus: what do we know so far?,10.1136/bmj.m308,,,,,2020,"Mahase, E.",BMJ (Clinical research ed.),3001211201,#151,
,CZI,The psychological effects of quarantining a city,10.1136/bmj.m313,,,,"Whether the epidemiological benefits of mandatory mass quarantine outweigh the psychological costs is a judgement that should not be made lightlyThe emergence of a novel form of coronavirus in Wuhan, China, is creating a confused and rapidly evolving situation. As ever in the early stages of a major incident, facts are unclear. We’re not sure how many people have caught the disease, the fatality rate, the incubation period, how far it’s spread—or how worried we should be. The imposition of travel restrictions on Wuhan—and an expanding number of other cities—has surprised many. The move has left over 20 million people caught in a modern form of quarantine. Regardless of whether it succeeds in controlling the outbreak, the widespread lockdown will inevitably have a psychological effect. Not surprisingly, the UK media are already reporting the emotional impact of both the outbreak and the response. Residents are said to be comparing the situation to “the end of the world,” hospitals are “overwhelmed,” and there are concerns about food shortages. “Panic in Wuhan” is commonly reported.We must be careful of …",2020,"Rubin, G. James; Wessely, Simon",BMJ,3003379403,#163,
,CZI,"China coronavirus: mild but infectious cases may make it hard to control outbreak, report warns",10.1136/bmj.m325,,,,"Uncertainty over the severity spectrum of the novel coronavirus (2019-nCoV) and whether people with mild symptoms can efficiently transmit the virus mean it is currently “unclear” whether the outbreak can be contained within China, a report from Imperial College London has warned.1The update from the MRC Centre for Global Infectious Disease Analysis said that the rate of transmission could come down as people become aware of the threat and try to avoid becoming infected, as happened with severe acute respiratory syndrome (SARS).But it raised concerns over reports of mildly symptomatic but infectious cases, which were not a feature of SARS. Detecting and …",2020,"Mahase, Elisabeth",BMJ,3003233446,#180,
,CZI,Chinese premier rallies medics in coronavirus fight,10.1136/bmj.m343,,,,"Xinhua/Li Tao/PAChina’s premier, Li Keqiang (centre), visited the Wuhan Jinyintan Hospital this week to see the team’s work to control the outbreak of the novel coronavirus in the area.Li arrived on 27 January …",2020,"Moberly, Tom",BMJ,3003294398,#178,
,CZI,"Following the evidence, from coronavirus to terrorism response",10.1136/bmj.m344,,,,"The emergence of a novel coronavirus has led China to impose travel restrictions around Wuhan and other cities (doi:10.1136/bmj.m349). Yet, as G James Rubin and Simon Wessely point out (doi:10.1136/bmj.m313), we don’t not know whether the potential benefits of mandatory mass quarantine outweigh the psychological costs of such an intervention to the people affected. Elisabeth Mahase summarises what we know so far about the virus and its effects (doi:10.1136/bmj.m308); clearly there is much we …",2020,"Moberly, Tom",BMJ,3003277976,#179,
,CZI,"China coronavirus: partial border closures into Hong Kong are not enough, say doctors",10.1136/bmj.m349,,,,"As the novel coronavirus (2019-nCOV) outbreak rapidly expands across the border in mainland China, healthcare workers in Hong Kong are bracing for a potential explosion of cases locally and have urged the government to severely restrict arrivals from mainland China or even to close the border completely.Eight cases were confirmed in Hong Kong as of 27 January, and 38% of the 663 beds in the negative pressure wards, which are used to isolate patients at public hospitals, were already in use, said officials. They expressed concern that the public health system might be overwhelmed if a local “super-spreader” event occurs or by people from mainland China coming into Hong Kong to seek treatment.On 28 January Carrie Lam, Hong Kong chief executive, announced a partial border closure, halting all cross border rail routes from midnight on 30 January, as well as a suspension of six border checkpoints, suspension of ferries, gradual reduction of cross border flights from 480 a …",2020,"Parry, Jane",BMJ,3004279122,#175,
,CZI,Wuhan: Britons to be evacuated as scientists estimate 44 000 cases of 2019-nCOV in the city,10.1136/bmj.m351,,31996342,,,2020,"Parry, J.",BMJ (Clinical research ed.),3003684729,#86,
,CZI,Coronavirus shows how UK must act quickly before being shut out of Europe’s health protection systems,10.1136/bmj.m400,,,,"The threat posed by 2019-nCoV and the fragmentation of existing health protection systems caused by Brexit call for urgent assessment of cross Europe cooperation, say Mark Flear, Anniek de Ruijter, and Martin McKeeHealth authorities worldwide are racing to contain the spread of the coronavirus 2019-nCoV, identified as the cause of the outbreak that began in Wuhan, China, at the end of last year. By 31 January more than 9600 people were reported to have been infected in China, with around 200 deaths, and cases have also been reported elsewhere in Asia and in North America, Australia, and Europe, including France, Finland, Germany, and now the UK.1 The case in Germany is especially worrying as it was in someone who had not travelled to China but who had been in contact with someone who had. Unprecedented measures, including lockdowns of large cities in China and widespread flight cancellations, are being adopted.The international response to major outbreaks of infectious disease is coordinated by the World Health Organization and is based on its International Health Regulations.2 Europe also has a regime for communicable disease control,3 centred on the Stockholm based European Centre for Disease Prevention and Control (ECDC), which has a crucial role in responding to threats to health in the continent.Given the UK’s departure from the European Union, we argue that the coronavirus outbreak is an urgent warning highlighting the need to reflect on what Brexit might mean for the country’s health security. We review how that system operates and what the implications might be for the UK. In doing so we draw on the experience of Switzerland. Like a post-Brexit UK, Switzerland is outside …",2020,"Flear, Mark; de Ruijter, Anniek; McKee, Martin",BMJ,,#196,
,CZI,Response to the emerging novel coronavirus outbreak,10.1136/bmj.m406,,32005675,,,2020,"Kickbusch, I.; Leung, G.",BMJ (Clinical research ed.),3003585850,#96,
,CZI,China coronavirus: WHO declares international emergency as death toll exceeds 200,10.1136/bmj.m408,,,,"The World Health Organization has declared the current novel coronavirus (2019-nCoV) outbreak to be a public health emergency of international concern, as latest figures show that nearly 10 000 people have been infected and that over 200 have died.WHO’s emergency committee reconvened on 30 January—a week after it first met—to reassess the situation. Tedros Adhanom Ghebreyesus, WHO director general, said that the declaration was “not because of what is happening in China but because of what is happening in other countries.”He warned, “Our greatest concern is for the virus to spread to countries with weaker health systems that are ill prepared to deal with it.”The announcement …",2020,"Mahase, Elisabeth",BMJ,3003977029,#181,
,CZI,"Coronavirus latest: death toll passes 2,000",10.1136/bmj.m408,,,,"Updates on the respiratory illness that has infected tens of thousands of people. Scientists are concerned about a new virus that has infected tens of thousands of people and killed more than 2,000. The virus, which emerged in the Chinese city of Wuhan in December, is a coronavirus and belongs to the same family as the pathogen that causes severe acute respiratory syndrome, or SARS. It causes a respiratory illness called COVID-19, which can spread from person to person.",2020,Nature,Nature,3003977029,#1372,
,CZI,China coronavirus: Hong Kong health staff strike to demand border closure as city records first death,10.1136/bmj.m454,,,,"Hong Kong has reported its first death related to the novel coronavirus 2019-nCoV, only the second fatality reported outside mainland China, as healthcare workers in the city started unprecedented industrial action to put pressure on the government to close the border and avert an escalation in the number of infections.The 39 year old man, who had an underlying health condition, had travelled to Wuhan on 21 January. In late January, after his return to Hong Kong, he developed fever and myalgia. The Hong Kong Hospital Authority announced that he had died on 3 February. The news coincided with the second day of industrial action by members of the Hospital Authority Employees’ Alliance, a new labour union representing around 9000 of the 67 000 staff employed by the Hospital Authority, the statutory body that manages all of Hong Kong’s government hospitals.After a strike by 2700 non-essential staff on 2 February, the …",2020,"Parry, Jane",BMJ,3005117448,#221,
,CZI,"China coronavirus should be on “everybody’s agenda,” says vaccine expert",10.1136/bmj.m476,,,,"Novel coronavirus (2019-nCoV) should be on “everybody’s agenda,” says Seth Berkley, chief executive officer of Gavi, the Vaccine Alliance. He said that, while some responses may be “over-reaching,” what is currently known about the virus suggests that it should be treated seriously.Berkley, who spoke at a briefing in London on 4 February, told The BMJ that, although we “do not know enough right now to honestly answer the question [of over-reaction],” it is better to prepare now than to wait and see.“Does that mean that we should be having travel bans everywhere in the world and all of those other responses? I think there are certainly things that are over-reaching, but I think that the world is taking …",2020,"Mahase, Elisabeth",BMJ,,#295,
,CZI,Novel coronavirus: Australian GPs raise concerns about shortage of face masks,10.1136/bmj.m477,,,,"General practitioners in Australia have raised concerns over their safety and the safety of their teams because of the lack of protective equipment, including masks, which they said are needed to respond confidently to the novel coronavirus outbreak.Medical equipment suppliers have posted notices on their websites stating that they are no longer accepting orders of supplies such as masks, and GPs have told The BMJ that they are struggling to get hold of the supplies they need. The Royal Australian College of General Practitioners (RACGP) said that the recent bushfires had led to …",2020,"Mahase, Elisabeth",BMJ,3004966978,#296,
,CZI,"In Beijing, coronavirus 2019-nCoV has created a siege mentality",10.1136/bmj.m516,,32033967,,,2020,"Mowbray, Heather",BMJ,3005442318,#547,
,CZI,Coronavirus: doctor who faced backlash from police after warning of outbreak dies,10.1136/bmj.m528,,,,"Li Wenliang—a doctor from Wuhan, China, who said he was reprimanded by police for warning other doctors about novel coronavirus at the start of the outbreak—has died after being infected with 2019-nCoV.When the first cases of a pneumonia-like condition appeared in a local hospital, Li sent messages to his medical school alumni group on the Chinese messaging app WeChat, warning that, from the test results he had …",2020,"Mahase, Elisabeth",BMJ,3004702727,#388,
,CZI,"Coronavirus: global stocks of protective gear are depleted, with demand at “100 times” normal level, WHO warns",10.1136/bmj.m543,,,,"The demand for personal protective equipment such as masks and respirators is 100 times the normal level, and costs have skyrocketed to around 20 times their usual price, the World Health Organization has reported. WHO warned of “severe disruption” in the market for personal protective equipment and said that worldwide stocks were “now insufficient” to meet demand. The warning came from WHO’s director general, Tedros Adhanom Ghebreyesus, during his opening remarks at a briefing on 2019-nCoV on 7 February. He said that the situation had been “exacerbated by widespread, inappropriate use of personal protective equipment outside patient care.” This has led to “depleted stockpiles and backlogs of four to six months.” Last week The BMJ reported that GPs in Australia were finding it difficult to get the protective masks they needed because of shortages The demand for personal protective equipment such as masks and respirators is 100 times the normal level, and costs have skyrocketed to around 20 times their usual price, the World Health Organization has reported.WHO warned of “severe disruption” in the market for personal protective equipment and said that worldwide stocks were “now insufficient” to meet demand. The warning came from …",2020,"Mahase, Elisabeth",BMJ,,#599,
,CZI,Seven days in medicine: 5-11 Feb 2020,10.1136/bmj.m548,,,,"UK declares “serious and imminent threat to public health”The UK government declared that the “incidence or transmission of novel coronavirus constitutes a serious and imminent threat to public health.” The announcement on 10 February means that England’s health secretary, Matt Hancock, can enact regulations to ensure that people are “protected as far as possible from the transmission of the virus.” This includes designating Arrowe Park Hospital in Merseyside and Kents Hill Park in Milton Keynes as isolation facilities. As of 10 February eight people in the UK had tested positive for 2019-nCoV.More UK laboratories get diagnostic testingPublic Health England (PHE) announced that it was rolling out its novel coronavirus diagnostic test to 12 laboratories in England, Scotland, Wales, and Northern Ireland over the next few weeks, bringing the total facilities with testing capability to 13. This will increase the testing capacity in England from 100 to 1000 people a day. The test is performed on a sample from the nose, throat, and respiratory tract. A confirmatory test will continue to be conducted at PHE’s Colindale laboratories in north London. PHE is also working with the World Health Organization to test samples from countries that do not have testing facilities.Global stocks of protective gear are depletedThe demand for personal protective equipment such as masks and respirators is 100 times the normal level, and costs have skyrocketed to around 20 …",2020,,BMJ,2903965036,#806,
,CZI,Coronavirus: NHS staff get power to keep patients in isolation as UK declares “serious threat”,10.1136/bmj.m550,,,,"The UK government has declared that the incidence or transmission of the novel coronavirus 2019-nCoV constitutes a serious and imminent threat to public health. The announcement means that England’s health secretary, Matt Hancock, can enact regulations to ensure that the public is “protected as far as possible from the transmission of the virus.” This includes designating Arrowe Park Hospital, Merseyside, and the Kents Hill Park hotel and conference centre, Milton Keynes, as isolation facilities. It also means that NHS staff members have “strengthened powers” to keep patients in isolation if public health professionals believe there to be a “reasonable risk an individual may have the virus.” As at 10 February eight people in the UK had tested positive for 2019-nCoV. Globally, the virus has spread to 28 countries, with more than 40 000 cases and 900 deaths. The UK government has declared that the incidence or transmission of the novel coronavirus 2019-nCoV constitutes a serious and imminent threat to public health.The announcement means that England’s health secretary, Matt Hancock, can enact regulations to ensure that the public is “protected as far as possible from the transmission of the virus.” This includes designating Arrowe Park Hospital, Merseyside, and the Kents Hill Park hotel and conference centre, Milton Keynes, as isolation facilities.It also means that NHS staff members have “strengthened powers” to keep patients in isolation if public health professionals believe there to be a “reasonable risk an individual may have the virus.”As at 10 February eight people in the UK had tested positive for 2019-nCoV. Globally, the virus has spread to 28 countries, with more than 40 000 cases …",2020,"Mahase, Elisabeth",BMJ,,#600,
,CZI,"Coronavirus: online GP bookings should be stopped because of safety risks, warns BMA",10.1136/bmj.m611,,,,"General practices should be able to turn off their online booking systems in response to the covid-19 outbreak without fear of repercussions over breaching their contract, the BMA has told NHS England.Practices are contractually obliged to provide 25% of their appointments through online booking; as this system does not triage patients in the same way that a receptionist does, however, the BMA has warned that it could …",2020,"Mahase, Elisabeth",BMJ,3005624666,#876,
,CZI,Coronavirus: home testing pilot launched in London to cut hospital visits and ambulance use,10.1136/bmj.m621,,,,"People with suspected covid-19 in London are being tested in their homes as part of a pilot that was developed by doctors to stop unnecessary ambulance use and hospital visits.The community testing scheme started at the end of January at North West London NHS Trust and has now been implemented in three other trusts: University College London Hospital, St George’s University Hospital, and Guys and St Thomas’. More than 130 patients have been tested in two weeks.The home testing initiative was started by Laurence John from the infectious diseases department at Northwick Park Hospital. He told The BMJ that the need for community testing became clear after 25 London ambulances had to be taken out of …",2020,"Mahase, Elisabeth",BMJ,3006625193,#942,
,CZI,What did we learn from Tamiflu?,10.1136/bmj.m626,,,,"Ten years after questions were first raised over its effectiveness, Owen Dyer charts the fortunes of this blockbuster pill and finds that lack of evidence has not dented its successGovernments cannot calm earthquakes, bottle up volcanoes, or hold back tsunamis—they may not even be able to put out wildfires—but one disaster they do claim to have power over is a flu epidemic. Since the first pandemic scare of this century, H5N1 avian influenza in 2004 (see timeline, box 1), governments have been stockpiling the neuraminidase inhibitors zanamivir (Relenza) and especially oseltamivir (Tamiflu), in vast quantities.Box 1 Oseltamivir and pandemic flu preparedness—key events 2003—US adds oseltamivir to its strategic national stockpile2004—First outbreak of H5N1 avian flu in humans2005—UK announces it will stockpile 14 million doses of oseltamivir2006—Cochrane review concludes that oseltamivir reduces complications and symptoms in seasonal flu2009—H1N1 swine flu pandemic declared by WHO2009—The BMJ publishes critical Cochrane update review of oseltamivir2011—FOI request results in European Medicines Agency releasing 20 000 pages of oseltamivir data2013—GSK and Roche release trial data on zanamivir and oseltamivir2014—Cochrane review finds insufficient evidence that oseltamivir reduces lower respiratory complications or impedes transmission2016—Generic formulations of oseltamivir become available2017—WHO downgrades status of oseltamivir2020—Cochrane team member Thomas Jefferson sues Roche in US for wrongfully billing public health authorities for oseltamivir as a pandemic response drugRETURN TO TEXTThe UK, the US, and many other countries hold enough stocks of these antivirals to offer courses of treatment to a quarter of their population. The practice is almost ubiquitous in rich countries. Of 28 European states that have published a pandemic response plan, all but one (Poland) make oseltamivir the mainstay of their response until a vaccine can be developed.In the public mind, and the minds of politicians, the flu pandemic problem is one that has …",2020,"Dyer, Owen",BMJ,3001941086,#1315,
,CZI,Covid-19: a puzzle with many missing pieces,10.1136/bmj.m627,,,,"Better information on epidemiology, pathogenesis, and treatments are urgent prioritiesBy 15 February 2020, 51 800 cases of the novel coronavirus disease (formerly known as 2019-nCoV and renamed covid-19), including more than 1600 deaths, had been confirmed in China, mainly in Hubei province. A further 526 laboratory confirmed cases have been reported across 25 other countries.1 As is usual in the early phase of a disease outbreak, the alarm was raised as a result of the most severe cases, and the first reports describe severe pneumonia in patients admitted to hospital.2In a linked paper, Xu and colleagues (doi:10.1136/bmj.m606) report a case series of 62 patients (median age 41 years) admitted to hospital in the Zhejiang province with laboratory confirmed infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for covid-19.3 All the patients presented with respiratory symptoms, fever or flu-like illness, or both, and all had travelled to Wuhan or been in contact with a patient with confirmed covid-19 while staying in Wuhan. All but one had radiologically confirmed pneumonia, but only one patient was subsequently admitted to an intensive care unit …",2020,"Vetter, Pauline; Eckerle, Isabella; Kaiser, Laurent",BMJ,1976382352,#1267,
,CZI,Coronaviruses in animals and humans,10.1136/bmj.m634,,,,"Controlling outbreaks will require detailed knowledge of their biology and behaviourCoronaviruses have been around for many years and were first discovered in the 1960s. They include viruses contributing to the common cold (HCoV-229E) and a variety of animal and avian coronaviruses, such as infectious bronchitis virus (IBV), which infects poultry. Coronaviruses typically cause respiratory or gastrointestinal illness, but strains of IBV have been shown to target the oviduct in chickens, and others can cause severe kidney disease.Animal and avian coronaviruses can have high mortality rates among infected animals and illustrate the difficulties in developing vaccines. Similar to influenza viruses, despite many decades of research there is no vaccine that protects against all strains of IBV coronavirus. This is due in part to the continuously shifting diversity in the virus spike glycoprotein, a major immunogenic target and hence a good vaccine candidate for animal and human infections.During the mid-1990s these viruses were described as the backwater of virology, since none caused serious disease in humans. However, this changed in 2002-03 with …",2020,"Ng, Lisa F. P.; Hiscox, Julian A.",BMJ,2577028059,#1281,
,CZI,"Coronavirus covid-19 has killed more people than SARS and MERS combined, despite lower case fatality rate",10.1136/bmj.m641,,,,"The novel coronavirus that has so far spread from China to 26 countries around the world does not seem to be as “deadly as other coronaviruses including SARS and MERS,” the World Health Organization has said.At a briefing on 17 February WHO’s director general, Tedros Adhanom Ghebreyesus, said that more than 80% of patients with covid-19 have a “mild disease and will recover” and that it is fatal in 2% of reported cases. In comparison, the 2003 outbreak of severe acute respiratory syndrome (SARS) had a case fatality rate of around 10% (8098 cases and 774 deaths), while Middle East respiratory syndrome (MERS) killed 34% of people with the illness …",2020,"Mahase, Elisabeth",BMJ,3006642361,#1245,
,CZI,"Letter from China: covid-19 on the grapevine, on the internet, and in commerce",10.1136/bmj.m643,,,,"In medically murky times in China, people are turning to rumour, hope, and faith to protect themselves from the new coronavirus. In Beijing, Heather Mowbray is hearing all sorts of stories about how to stop the virus—but scientific evidence for the advice is woefully absentHere’s one example of the ideas floating around in China. Radio Free Asia reported that a Tibetan man named Tse was encouraging people to recite and forward a Buddhist prayer as a safeguard against the new coronavirus, covid-19. He was arrested for his efforts. Spreading rumours can land you in jail for seven years.Community imposed social isolation means that everyone has plenty of time to read the latest news and advice online. Children have web based schooling, and adults do their searches from the kitchen table. The news aggregator Jinri Toutiao has leapt to the top of the app download list in the past month. …",2020,"Mowbray, Heather",BMJ,3005550222,#1282,
,CZI,Coronavirus: Wales tests 90% of suspected patients in their own home,10.1136/bmj.m698,,,,"Wales has managed to test 90% of people suspected of being infected with novel coronavirus in their own homes, after implementing community testing for covid-19.Vaughan Gething, minister for health and social services in Wales, credited the NHS with making the process “as convenient as possible for people whilst also protecting our ambulance and hospital resources for those who need it most.”More than 100 people had been tested in Wales as of 13 February, with no positive cases. Around the UK, nine …",2020,"Mahase, Elisabeth",BMJ,1968634965,#1376,
,CZI,Rules on isolation rooms for suspected covid-19 cases in GP surgeries to be relaxed,10.1136/bmj.m707,,32086235,,,2020,"Kmietowicz, Zosia",BMJ,2171042902,#1604,
,CZI,Covid-19: surge in cases in Italy and South Korea makes pandemic look more likely,10.1136/bmj.m751,,32098875,,,2020,"Day, Michael",BMJ,2317219333,#2311,
,CZI,Covid-19: Italy confirms 11 deaths as cases spread from north,10.1136/bmj.m757,,32102793,,,2020,"Day, M.",BMJ (Clinical research ed.),2742206604,#2785,
,CZI,Healthcare information for all,10.1136/bmj.m759,,,,"Together, we can stop people dying from a lack of timely accurate healthcare information The World Medical Association (WMA) has unanimously approved a statement on healthcare information for all, proposed by the British Medical Association.1 The statement notes that lack of access to timely, current, evidence based healthcare information continues to be a major contributor to morbidity and mortality, especially in low and middle income countries, and calls on doctors worldwide to support initiatives to improve access for health professionals, patients, and the public. The BMJ hosted a conference on this issue in 19942 and cofounded Hinari in 2001, a partnership between publishers and the World Health Organization to improve the availability of e-journals and e-books in low and middle income countries.3 In 2004 we coauthored a paper in the Lancet describing the global healthcare information system and its interdependent parts.4 We called for a global campaign to support communication, understanding, and advocacy among all stakeholders. These include researchers, journal publishers, systematic reviewers, guideline developers, publishers of secondary materials (from textbooks to radio shows), those who guide and provide access (from search engines to librarians), and all who share the vision of a world where everyone has access to the information they need to protect their own and others’ health. Healthcare Information For All (HIFA) now has 20 000 members …",2020,"Pakenham-Walsh, Neil; Godlee, Fiona",BMJ,2057196240,#4937,
,CZI,Covid-19: a digital epidemic,10.1136/bmj.m764,,,,"The covid-19 epidemic is not only viral—it is also digital.1Information spread through social and traditional media, as well as through governmental or health agencies, has reached …",2020,"Chiolero, Arnaud",BMJ,3006419170,#3197,
,CZI,"Covid-19: Trump says risk to Americans is ""very low""",10.1136/bmj.m793,,32107254,,,2020,"Tanne, J. H.",BMJ (Clinical research ed.),2170383333,#2957,
,CZI,"Covid-19: preparedness, decentralisation, and the hunt for patient zero",10.1136/bmj.m799,,32111645,,,2020,"Carinci, F.",BMJ (Clinical research ed.),3005981248,#2748,
,CZI,Coronavirus disease 2019 (covid-19): a guide for UK GPs,10.1136/bmj.m800,,,,"What you need to knowConsider covid-19 infection in anyone with cough, fever, or breathlessness who has had contact with someone with covid-19, or has returned from a high risk area in the 14 days before the onset of symptomsEvery effort should be made to avoid in-person assessment of patients with possible covid-19 in primary careGP surgeries should plan ahead and develop clear protocols for managing possible cases, including isolation procedures, personal protective equipment, seeking specialist advice, and decontaminationIf covid-19 infection is suspected in someone attending the practice, isolate the patient in a room (away from other patients and staff), close the door, and ask the patient to call NHS 111The guidance may change so it is essential to look at the latest guidance online (box 1)The UK recorded its first confirmed case of acute respiratory infection due to coronavirus disease 2019 (covid-19) on 31 January 2020 and responded by quarantining at-risk individuals to contain the spread of infection. Executive agencies Public Health England (PHE)1 and Health Protection Scotland (HPS) have since published guidance to healthcare providers on managing patients suspected to have the disease.Guidance for the public and health professionals varies internationally, depending partly on risk levels and healthcare systems, and is being regularly updated.This article offers a practical guide for GPs and others working in UK primary care on when to suspect covid-19 and how to respond. It is based on current UK guidance at the time of publication. We recommend readers consult the latest guidance (box 1).Box 1 Essential resourcescovid-19: latest case definition, investigation, and initial clinical management of possible cases:https://www.gov.uk/government/publications/wuhan-novel-coronavirus-initial-investigation-of-possible-cases/investigation-and-initial-clinical-management-of-possible-cases-of-wuhan-novel-coronavirus-wn-cov-infectionCoronavirus: latest information and advice including updated list of high risk countries:https://www.gov.uk/guidance/wuhan-novel-coronavirus-information-for-the-publicGuidance on isolation of healthcare workers:https://www.gov.uk/government/publications/novel-coronavirus-2019-ncov-guidance-for-healthcare-providers-with-staff-who-have-travelled-to-china/guidance-for-healthcare-providers-healthcare-workers-who-have-travelled-to-chinaFind your local Health Protection Team in England:https://www.gov.uk/health-protection-teamcovid-19: interim guidance … RETURN TO TEXT",2020,"Razai, Mohammad S.; Doerholt, Katja; Ladhani, Shamez; Oakeshott, Pippa",BMJ,2604381070,#4464,
,CZI,"Covid-19: school closures and bans on mass gatherings will need to be considered, says England's CMO",10.1136/bmj.m806,,32111656,,,2020,"Moberly, T.",BMJ (Clinical research ed.),2738470870,#2902,
,CZI,Preventing a covid-19 pandemic,10.1136/bmj.m810,,32111649,,,2020,"Watkins, J.",BMJ (Clinical research ed.),3005847234,#2972,
,CZI,Sixty seconds on . . . beards,10.1136/bmj.m811,,,,"Now calm down, we’re not about to start dolling out fashion tips for your facial fuzz. We’re talking about how having a hairy face could stop protective face masks from fitting properly.It can do. Derek Sandeman, the medical director of the University Hospital Southampton NHS Foundation Trust, has written to his clinical staff asking anyone working in high risk …",2020,"Rimmer, Abi",BMJ,3004180009,#3316,
,CZI,"Covid-19: retired doctors could be asked to return to work, says Hancock",10.1136/bmj.m831,,32122881,,,2020,"Mahase, Elisabeth",BMJ,2330696540,#3334,
,CZI,"Covid-19: US health department staff sent to meet citizens returning from China weren't protected, claims whistleblower",10.1136/bmj.m833,,32122875,,,2020,"Dyer, Owen",BMJ,2612454967,#3410,
,CZI,Covid-19: UK could delay non-urgent care and call doctors back from leave and retirement,10.1136/bmj.m854,,,,"Healthcare staff on leave and those who have retired could be called “back to duty,” and non-urgent care could be delayed, as doctors are forced to prioritise dealing with covid-19, the UK government’s action plan lays out.The government will also implement a “distribution strategy for the UK’s stockpiles of key medicines and equipment (e.g. protective clothing),” the document said.However, the plan did not include details of how or when these measures would be …",2020,"Mahase, Elisabeth",BMJ,2151773763,#3336,
,CZI,Prepare for a pandemic,10.1136/bmj.m864,,,,"A covid-19 pandemic is highly likely, warns our editorialist, the epidemiologist John Watkins (doi:10.1136/bmj.m810), and we need to plan now how to reconfigure care services to cope with the looming escalation in demand. “We should plan on the assumption that most of the population may contract the virus with few or no long term effects,” he writes, “while harnessing vital secondary healthcare resources to treat the small percentage of people who become seriously ill.”As at Tuesday 3 March the UK had confirmed 51 cases of infection (doi: …",2020,"Hurley, Richard",BMJ,2091233622,#4551,
,CZI,"Covid-19: hoarding and misuse of protective gear is jeopardising the response, WHO warns",10.1136/bmj.m869,,,,"Nearly 90 million face masks are required every month to protect health staff as they tackle covid-19, the World Health Organization has estimated, as it warned that current supplies were “rapidly depleting.”The ability of countries to respond to the outbreak is being compromised by the “severe and increasing disruption to the global supply of personal protective equipment—caused by rising demand, hoarding, and misuse,” said WHO’s director general, Tedros Adhanom Ghebreyesus.Speaking at the daily press briefing on 3 March, he warned …",2020,"Mahase, Elisabeth",BMJ,3005244019,#3826,
,CZI,"Covid-19: 90% of cases will hit NHS over nine week period, chief medical officer warns",10.1136/bmj.m918,,,,"Nearly all covid-19 cases will hit the NHS in a “heavily concentrated” burst, with 50% of cases predicted to happen over a three week period and 90% over nine weeks, says the chief medical officer for England, Chris Whitty.Speaking to the Health and Social Care Committee on 5 March, Whitty said that the NHS would be put under huge pressure and would have to push some routine care to before or after the expected peak of cases.Adding more detail to the government’s suggestion1 that retired doctors could be called “back to duty,” he said that doctors who had retired in the past two to three years would be considered and that he was “confident” that many would …",2020,"Mahase, Elisabeth",BMJ,2197453954,#4499,
,CZI,Covid-19: are we getting the communications right?,10.1136/bmj.m919,,32144115,,,2020,"Cowper, A.",BMJ (Clinical research ed.),3006304371,#5160,
,CZI,Covid-19: GP surgeries close for two weeks after staff test positive,10.1136/bmj.m936,,32144111,,,2020,"Iacobucci, G.",BMJ (Clinical research ed.),2048387827,#4739,
,CZI,Trump claims public health warnings on covid-19 are a conspiracy against him,10.1136/bmj.m941,,32144176,,,2020,"Dyer, O.",BMJ (Clinical research ed.),3005995896,#5189,
,CZI,"Covid-19: UK records first death, as world's cases exceed 100 000",10.1136/bmj.m943,,32144096,,,2020,"Mahase, E.",BMJ (Clinical research ed.),2332386010,#4882,
,CZI,Diarrhoea may be underestimated: a missing link in 2019 novel coronavirus,10.1136/gutjnl-2020-320832,,32102928,,,2020,"Liang, W.; Feng, Z.; Rao, S.; Xiao, C.; Xue, X.; Lin, Z.; Zhang, Q.; Qi, W.",Gut,3005757890,#2880,
,CZI,SARS-CoV-2 induced diarrhoea as onset symptom in patient with COVID-19,10.1136/gutjnl-2020-320891,,32139552,,,2020,"Song, Y.; Liu, P.; Shi, X. L.; Chu, Y. L.; Zhang, J.; Xia, J.; Gao, X. Z.; Qu, T.; Wang, M. Y.",Gut,2093565992,#5236,
,CZI,Where did SARS-CoV-2 come from?,10.1136/vr.m740,,32108071,,,2020,"Zhai, S. L.; Wei, W. K.; Lv, D. H.; Xu, Z. H.; Chen, Q. L.; Sun, M. F.; Li, F.; Wang, D.",The Veterinary record,2606000111,#3017,
,CZI,Advantages and challenges of metagenomic next-generation sequencing (mNGS) in the detection of 2019 novel coronavirus,10.1146/annurev-pathmechdis-012418-012751,,,,"As one of the two methods for 2019 novel coronavirus (2019-nCoV), gene sequencing is different from quantitative real-time PCR (RT-PCR) in detection principles. Therefore, gene sequencing has its own pros and cons in clinical application. Currently, metagenomic next-generation sequencing (mNGS) is the most commonly used technology in clinical application. Due to its broad coverage of all types of pathogens, mNGS demonstrates incomparable advantage in rapid identification of novel pathogens such as 2019-nCoV. In addition, it can simultaneously identify other pathogens except 2019-nCoV and mixed infections. On the other hand, however, due to the complexity of mNGS and long detection time, it is unlikely to achieve the purpose of wide-range and rapid diagnosis of 2019 n-CoV. Therefore, mNGS can complement RT-PCR to achieve best clinical application.",2020,"TAO, Yue; FU, Qihua; MO, Xi",Chinese Journal of Laboratory Medicine,2898604559,#2380,
,CZI,CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV),10.1148/radiol.2020200230,,32017661,,"In this retrospective case series, chest CT scans of 21 symptomatic patients from China infected with the 2019 Novel Coronavirus (2019-nCoV) were reviewed with emphasis on identifying and characterizing the most common findings. Typical CT findings included bilateral pulmonary parenchymal ground-glass and consolidative pulmonary opacities, sometimes with a rounded morphology and a peripheral lung distribution. Notably, lung cavitation, discrete pulmonary nodules, pleural effusions, and lymphadenopathy were absent. Follow-up imaging in a subset of patients during the study time window often demonstrated mild or moderate progression of disease as manifested by increasing extent and density of lung opacities.",2020,"Chung, Michael; Bernheim, Adam; Mei, Xueyan; Zhang, Ning; Huang, Mingqian; Zeng, Xianjian; Cui, Jiufa; Xu, Wenjian; Yang, Yang; Fayad, Zahi; Jacobi, Adam; Li, Kunwei; Li, Shaolin; Shan, Hong",Radiology,3004906315,#333,
,CZI,CT Imaging of the 2019 Novel Coronavirus (2019-nCoV) Pneumonia,10.1148/radiol.2020200236,,32003646,,,2020,"Lei, J.; Li, J.; Li, X.; Qi, X.",Radiology,3003901880,#141,
,CZI,2019 novel coronavirus (2019-nCoV) and 2019-nCoV pneumonia,10.1148/radiol.2020200236,,,,"In the middle of December in 2019, a pneumonia outbreak caused by a new coronavirus, 2019 novel coronavirus (2019-nCoV), emerged in the populations in Wuhan city of China. The epidemic spreads rapidly and has been disseminated throughout the country and to 13 other counties in Asia, Europe, Oceania and North America. To accurately and deeply understand the biological characteristics, epidemiological features and pathogenicity of 2019-nCoV and related immunological characteristics, microbiological examinations and public protection measure, this study reviewed 2019-nCoV and 2019-nCoV pneumonia based on the newest relevant literatures and the newest version of National Diagnosis and Treatment Scheme of 2019-nCoV pneumonia.",2020,"YAN, Jie; LI, Mingyuan; SUN, Aihua; PENG, Yihong",Chinese Journal of Microbiology and Immunology,3003901880,#2096,
,CZI,"Chest CT Findings in 2019 Novel Coronavirus (2019-nCoV) Infections from Wuhan, China: Key Points for the Radiologist",10.1148/radiol.2020200241,,32017662,,,2020,"Kanne, Jeffrey P.",Radiology,3005272159,#316,
,CZI,2019 Novel Coronavirus (2019-nCoV) Pneumonia,10.1148/radiol.2020200257,,32013795,,,2020,"Liu, Peng; Tan, Xian-Zheng",Radiology,3004826915,#304,
,CZI,"Evolution of CT Manifestations in a Patient Recovered from 2019 Novel Coronavirus (2019-nCoV) Pneumonia in Wuhan, China",10.1148/radiol.2020200269,,32032497,,,2020,"Shi, Heshui; Han, Xiaoyu; Zheng, Chuansheng",Radiology,3004511262,#494,
,CZI,CT features of 2019-novel coronovirus pneumonia: SARS and MERS literature review and analysis of CT features of two confirmed 2019-novel coronavirus pneumonia cases,10.1148/radiol.2020200269,,,,"Objective To analyze the CT manifestations of the 2019 novel coronavirus pneumonia (NCP) combined with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) literature review, and to summarize the characteristics of CT imaging, so as to improve the ability of rapid and accurate diagnosis. Methods CT manifestations of two confirmed cases of NCP were reported, meanwhile the literatures on SARS and MERS imaging performance were reviewed and summarized. Results The two cases of NCP were both in acute stage, the CT imaging showed multiple and scattered ground-glass opacity (GGO) in both lungs, which is similar to the CT performance of SARS and MERS in acute stage. Conclusions The CT features of 2019 novel coronavirus pneumonia are similar to SARS and MERS. It has certain characteristics and changes rapidly with the course of the disease. In the acute stage, GGO and paving stone sign were the main manifestations. In the acute phase, GGO and crazy paving are the main manifestations. In the progress stage, the interlobular septal thickening and consolidation appeared. During the absorption period, the lesions disappeared or fibrosis was left behind, with lung structure distortion and bronchiectasis. Lymphadenopathy and hydrothorax were rare.",2020,"YANG, Changwei; FAN, Chenghui; CHENG, Ailan; LIU, Jing; ZHU, Chongwen; HU, Bo; WANG, Rongfang; QU, Lihong; CHU, Shuguang",Chinese Critical Care Medicine,3004511262,#2094,
,CZI,Emerging Coronavirus 2019-nCoV Pneumonia,10.1148/radiol.2020200274,,32027573,,"Background The chest CT findings of patients with coronavirus 2019-nCoV pneumonia have not previously been described in detail. Purpose To investigate the clinical, laboratory, and imaging findings of emerging coronavirus 2019-nCoV pneumonia in humans. Materials and Methods Fifty-one patients (25 men and 26 women, 16-76 years old) with 2019-nCoV pneumonia confirmed with the positive new coronavirus nucleic acid antibody underwent thin-section CT. The imaging findings, clinical and laboratory data were evaluated. Results Fifty of 51 patients (98%) had a history of the endemic center Wuhan contact. Fever (49/51, 96%) and cough (24/51, 47%) were the most common symptoms. Most patients had a normal white blood cell count (37/51, 73%), neutrophil count (44/51, 86.3%) and normal (17/51, 35.3%) or reduced (33/51, 64.7%) lymphocyte count. CT images showed pure ground grass opacity (GGO) in 39/51 (77%) patients, GGO with reticular and/or interlobular septal thickening in 38/51 (75%) patients. GGO with consolidation was present in 30/51 (59%) and pure consolidation in 28/51 (55%) patients. 44/51 (86%) patients had bilateral lung involvement, while 41/51 (80%) involved the posterior part of the lungs and 44/51 (86%) were peripheral. There were more consolidated lung lesions in patients 5 or more days from disease onset to CT scan versus 4 or fewer days (431/712 lesions vs. 129/612 lesions, p < 0.001). Patients more than 50 years old had more consolidated lung lesions than those 50 years or younger (212/470 vs. 198/854, p < 0.001). Follow up CT in 13 patients showed improvement in 7 (54%) patients and progression in 4 (31%) patients. Conclusions Patients with fever and/or cough and with conspicuous ground grass opacity lesions in the peripheral and posterior lungs on CT images combined with normal or decreased white blood cells and a history of epidemic exposure are highly suspected of 2019-nCoV pneumonia.",2020,"Song, Fengxiang; Shi, Nannan; Shan, Fei; Zhang, Zhiyong; Shen, Jie; Lu, Hongzhou; Ling, Yun; Jiang, Yebin; Shi, Yuxin",Radiology,3004668429,#465,
,CZI,CT Manifestations of Two Cases of 2019 Novel Coronavirus (2019-nCoV) Pneumonia,10.1148/radiol.2020200280,,32031481,,,2020,"Fang, Yicheng; Zhang, Huangqi; Xu, Yunyu; Xie, Jicheng; Pang, Peipei; Ji, Wenbin",Radiology,3004802901,#495,
,CZI,Pre- and Posttreatment Chest CT Findings: 2019 Novel Coronavirus (2019-nCoV) Pneumonia,10.1148/radiol.2020200323,,32049602,,,2020,"Duan, Ya-Ni; Qin, Jie",Radiology,3006328792,#780,
,CZI,Use of Chest CT in Combination with Negative RT-PCR Assay for the 2019 Novel Coronavirus but High Clinical Suspicion,10.1148/radiol.2020200330,,32049600,,,2020,"Huang, Peikai; Liu, Tianzhu; Huang, Lesheng; Liu, Hailong; Lei, Ming; Xu, Wangdong; Hu, Xiaolu; Chen, Jun; Liu, Bo",Radiology,3005656138,#769,
,CZI,Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing,10.1148/radiol.2020200343,,32049601,,"Some patients with positive chest CT findings may present with negative results of real time reverse-transcription-polymerase chain- reaction (RT-PCR) for 2019 novel coronavirus (2019-nCoV). In this report, we present chest CT findings from five patients with 2019-nCoV infection who had initial negative RT-PCR results. All five patients had typical imaging findings, including ground-glass opacity (GGO) (5 patients) and/or mixed GGO and mixed consolidation (2 patients). After isolation for presumed 2019-nCoV pneumonia, all patients were eventually confirmed with 2019-nCoV infection by repeated swab tests. A combination of repeated swab tests and CT scanning may be helpful when for individuals with high clinical suspicion of nCoV infection but negative RT-PCR screening.",2020,"Xie, Xingzhi; Zhong, Zheng; Zhao, Wei; Zheng, Chao; Wang, Fei; Liu, Jun",Radiology,3006110666,#715,
,CZI,Time Course of Lung Changes On Chest CT During Recovery From 2019 Novel Coronavirus (COVID-19) Pneumonia,10.1148/radiol.2020200370,,32053470,,"Background Chest CT is used to assess the severity of lung involvement in COVID-19 pneumonia. Purpose To determine the change in chest CT findings associated with COVID-19 pneumonia from initial diagnosis until patient recovery. Materials and Methods This retrospective review included patients with RT-PCR confirmed COVID-19 infection presenting between 12 January 2020 to 6 February 2020. Patients with severe respiratory distress and/ or oxygen requirement at any time during the disease course were excluded. Repeat Chest CT was obtained at approximately 4 day intervals. The total CT score was the sum of lung involvement (5 lobes, score 1-5 for each lobe, range, 0 none, 25 maximum) was determined. Results Twenty one patients (6 males and 15 females, age 25-63 years) with confirmed COVID-19 pneumonia were evaluated. These patients under went a total of 82 pulmonary CT scans with a mean interval of 4±1 days (range: 1-8 days). All patients were discharged after a mean hospitalized period of 17±4 days (range: 11-26 days). Maximum lung involved peaked at approximately 10 days (with the calculated total CT score of 6) from the onset of initial symptoms (R2=0.25), p<0.001). Based on quartiles of patients from day 0 to day 26 involvement, 4 stages of lung CT were defined: Stage 1 (0-4 days): ground glass opacities (GGO) in 18/24 (75%) patients with the total CT score of 2±2; (2)Stage-2 (5-8d days): increased crazy-paving pattern 9/17 patients (53%) with a increase in total CT score (6±4, p=0.002); (3) Stage-3 (9-13days): consolidation 19/21 (91%) patients with the peak of total CT score (7±4); (4) Stage-4 (≥14 days): gradual resolution of consolidation 15/20 (75%) patients with a decreased total CT score (6±4) without crazy-paving pattern. Conclusion In patients recovering from COVID-19 pneumonia (without severe respiratory distress during the disease course), lung abnormalities on chest CT showed greatest severity approximately 10 days after initial onset of symptoms.",2020,"Pan, Feng; Ye, Tianhe; Sun, Peng; Gui, Shan; Liang, Bo; Li, Lingli; Zheng, Dandan; Wang, Jiazheng; Hesketh, Richard L.; Yang, Lian; Zheng, Chuansheng",Radiology,3006643024,#823,
,CZI,Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR,10.1148/radiol.2020200432,,32073353,,,2020,"Fang, Yicheng; Zhang, Huangqi; Xie, Jicheng; Lin, Minjie; Ying, Lingjun; Pang, Peipei; Ji, Wenbin",Radiology,2164629904,#1311,
,CZI,Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection,10.1148/radiol.2020200463,,32077789,,"In this retrospective study, chest CTs of 121 symptomatic patients infected with coronavirus disease-19 (COVID-19) from four centers in China from January 18, 2020 to February 2, 2020 were reviewed for common CT findings in relationship to the time between symptom onset and the initial CT scan (i.e. early, 0-2 days (36 patients), intermediate 3-5 days (33 patients), late 6-12 days (25 patients)). The hallmarks of COVID-19 infection on imaging were bilateral and peripheral ground-glass and consolidative pulmonary opacities. Notably, 20/36 (56%) of early patients had a normal CT. With a longer time after the onset of symptoms, CT findings were more frequent, including consolidation, bilateral and peripheral disease, greater total lung involvement, linear opacities, ""crazy-paving"" pattern and the ""reverse halo"" sign. Bilateral lung involvement was observed in 10/36 early patients (28%), 25/33 intermediate patients (76%), and 22/25 late patients (88%).",2020,"Bernheim, Adam; Mei, Xueyan; Huang, Mingqian; Yang, Yang; Fayad, Zahi A.; Zhang, Ning; Diao, Kaiyue; Lin, Bin; Zhu, Xiqi; Li, Kunwei; Li, Shaolin; Shan, Hong; Jacobi, Adam; Chung, Michael",Radiology,2055651857,#1690,
,CZI,Coronavirus Disease 2019 (COVID-19): A Perspective from China,10.1148/radiol.2020200490,,32083985,,"In December 2019, an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection occurred in Wuhan, Hubei Province, China and spread across China and beyond. On February 12, 2020, WHO officially named the disease caused by the novel coronavirus as Coronavirus Disease 2019 (COVID-19). Since most COVID-19 infected patients were diagnosed with pneumonia and characteristic CT imaging patterns, radiological examinations have become vital in early diagnosis and assessment of disease course. To date, CT findings have been recommended as major evidence for clinical diagnosis of COVID-19 in Hubei, China. This review focuses on the etiology, epidemiology, and clinical symptoms of COVID-19, while highlighting the role of chest CT in prevention and disease control. A full translation of this article in Chinese is available.",2020,"Zu, Zi Yue; Jiang, Meng Di; Xu, Peng Peng; Chen, Wen; Ni, Qian Qian; Lu, Guang Ming; Zhang, Long Jiang",Radiology,2604381070,#1419,
,CZI,Essentials for Radiologists on COVID-19: An Update-Radiology Scientific Expert Panel,10.1148/radiol.2020200527,,32105562,,,2020,"Kanne, J. P.; Little, B. P.; Chung, J. H.; Elicker, B. M.; Ketai, L. H.",Radiology,2800024516,#2856,
,CZI,Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases,10.1148/radiol.2020200642,,32101510,,"Background Chest CT is used for diagnosis of 2019 novel coronavirus disease (COVID-19), as an important complement to the reverse-transcription polymerase chain reaction (RT-PCR) tests. Purpose To investigate the diagnostic value and consistency of chest CT as compared with comparison to RT-PCR assay in COVID-19. Methods From January 6 to February 6, 2020, 1014 patients in Wuhan, China who underwent both chest CT and RT-PCR tests were included. With RT-PCR as reference standard, the performance of chest CT in diagnosing COVID-19 was assessed. Besides, for patients with multiple RT-PCR assays, the dynamic conversion of RT-PCR results (negative to positive, positive to negative, respectively) was analyzed as compared with serial chest CT scans for those with time-interval of 4 days or more. Results Of 1014 patients, 59% (601/1014) had positive RT-PCR results, and 88% (888/1014) had positive chest CT scans. The sensitivity of chest CT in suggesting COVID-19 was 97% (95%CI, 95-98%, 580/601 patients) based on positive RT-PCR results. In patients with negative RT-PCR results, 75% (308/413) had positive chest CT findings; of 308, 48% were considered as highly likely cases, with 33% as probable cases. By analysis of serial RT-PCR assays and CT scans, the mean interval time between the initial negative to positive RT-PCR results was 5.1 ± 1.5 days; the initial positive to subsequent negative RT-PCR result was 6.9 ± 2.3 days). 60% to 93% of cases had initial positive CT consistent with COVID-19 prior (or parallel) to the initial positive RT-PCR results. 42% (24/57) cases showed improvement in follow-up chest CT scans before the RT-PCR results turning negative. Conclusion Chest CT has a high sensitivity for diagnosis of COVID-19. Chest CT may be considered as a primary tool for the current COVID-19 detection in epidemic areas.",2020,"Ai, Tao; Yang, Zhenlu; Hou, Hongyan; Zhan, Chenao; Chen, Chong; Lv, Wenzhi; Tao, Qian; Sun, Ziyong; Xia, Liming",Radiology,3006110666,#2449,
,CZI,Helping the Radiologist: The Role of Scientific Journals to Help Prevent the Spread of COVID-19,10.1148/radiol.2020200661,,32125934,,,2020,"Li, Xiaohu; Qian, Yinfeng; Liu, Bin; Yu, Yongqiang",Radiology,230077627,#3358,
,CZI,Patients with RT-PCR Confirmed COVID-19 and Normal Chest CT,10.1148/radiol.2020200702,,32142398,,,2020,"Yang, W.; Yan, F.",Radiology,2894979147,#5367,
,CZI,FDG PET/CT of COVID-19,10.1148/radiol.2020200770,,32142399,,,2020,"Zou, S.; Zhu, X.",Radiology,2809328670,#5541,
,CZI,New coronavirus pneumonia and outbreak epidemic virus and eye disease,10.1155/2015/769121,,,,"Since the outbreak of the new coronavirus pneumonia (NCP) in Wuhan City, China, the main transmission mode as well as the diagnosis and treatment of NCP have become a focus of research in China and World Health Organizations. Understanding the mode of infection, transmission and biological behavior of the novel coronavirus (2019-nCoV) is undoubtedly a key of cutting off the spread and prevention of the disease which doctors are fearing to be a worldwide epidemic. In February 2019, Lancet published a correspondence paper, which reviewed a case of NCP patient who first started with conjunctivitis, and raised the issue that the transmission of 2019-nCoV through the ocular surface must not be ignored, causing widespread concern. However, due to a lack of clinical observation data and laboratory research at present, the relationship between NCP pathogen infection and ocular surface infection is not completely clear. So far, there have been many studies and reports on the observation of large-scale epidemic virus infections and eye diseases. This article reviews the eye performance of various types of epidemic virus infections and provides a reference for NCP prevention and control.",2020,"YIN, Shengjie; ZHANG, Mingzhi",Chinese Journal of Experimental Ophthalmology,2084228609,#2081,
,CZI,The treatment proposal for the patients with breast diseases in the central epidemic area of 2019 coronavirus disease,10.1158/1078-0432.CCR-10-2962,,32096395,,"Currently, the epidemic of 2019 coronavirus disease (COVID-19) is still ongoing. The characteristics including high contagiousness, herd susceptibility and clinical phenotype diversity, made a serious influence on people&rsquo;s daily life and rountine therapy for other diseases. Breast dieases are clinical common diseases. In the central epidemic area of COVID-19, Hubei province, especially Wuhan, the clinical specialists of breast diseases should consider all of the following factors comprehensively: the prevention of COVID-19, the diagnosis and treatment of breast diseases and the accessibility of medical resources. Besides, we should select the appropriate therapy and optimize treatment process so as to prevent the propagation and cross infection of COVID-19 as well as manage the breast diseases without delay. Therefore, we carried out some management proposals of the patients with breast diseases in the central epidemic area during the epidemic of COVID-19 on the basis of conventional treatment guidelines and clinical experiences. The suggestions and corrections from colleagues will be welcomed.",2020,"ZHAO, Lu; ZHANG, Lin; LIU, Jinwen; YANG, Zhifang; SHEN, Wenzhuang; LI, Xingrui",Chinese Journal of Surgery,2130735457,#1890,
,CZI,Outbreak of COVID-19 - an urgent need for good science to silence our fears?,10.11622/smedj.2020018,,32052064,,,2020,"Lum, Lionel Hw; Tambyah, Paul A.",Singapore Med J,3005969859,#818,
,CZI,The recommendation for management of the bereavements among the family members died with novel coronavirus pneumonia,10.1164/ajrccm-conference.2012.185.1_MeetingAbstracts.A4259,,,,"The death of a family member died with the novel coronavirus pneumonia is a special traumatic stress to the other family members and they will bear unbelievable distress and dramatic sorrow. The grief responses can be divided into normal grief responses and abnormal grief responses. The latter are much stronger, more severe, last longer and the responses can be delayed or inhibited or distorted. The management of abnormal grief responses includes counseling, supportive group, psychotherapy and medications.",2020,"JI, Jianlin",Chinese Journal of Behavioral Medicine and Brain Science,2324157363,#2248,
,CZI,Understanding the Influence Factors in Viral Nucleic Acid Test of 2019 novel Coronavirus (2019-nCoV),10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a5218,,,,"At present, the prevention and control of new coronavirus has entered a critical period. However, the use of quantitative real-time PCR (qRT-PCR) assays for the detection of viral nucleic acid, as a crucial diagnostic approach, has been doubted in clinical practice. Herein, we have reviewed the current status of epidemic prevention and control, latest development of detection technologies, disease characteristics, clinical sampling and transport. We have also discussed the factors that may affect the performance of viral nucleic acid detection, and suggested some effective methods to improve the detection performance of the assays.",2020,"XI, Mo; WEI, Qin; QIHUA, Fu; MING, Guan",Chinese Journal of Laboratory Medicine,2970372942,#2117,
,CZI,Novel Wuhan (2019-nCoV) Coronavirus,10.1164/rccm.2014P7,,32004066,,,2020,"Carlos, W. G.; Dela Cruz, C. S.; Cao, B.; Pasnick, S.; Jamil, S.",American journal of respiratory and critical care medicine,3003347489,#107,
,CZI,Visualising the expansion and spread of coronavirus disease 2019 by cartograms,10.1177/0308518X20910162,,,,"Coronavirus disease 2019 (COVID-19) has emerged as a growing focus of global attention and a critical factor in public-health decision making. Towards fighting the COVID-19 outbreak, countries worldwide and international organisations have taken various actions, including promoting the transparency of and public access to disease data. In such public communications, maps have played an important role in that a map is worth a thousand words. Most of these have taken the form of a choropleth map. Here, we propose employing cartograms to visualise both the expansion and spread of COVID-19. We designed a combination of six circular cartograms containing the data of confirmed cases every 48 hours from 24 January to 3 February 2020. Such a design conveys both spatial and temporal information more intuitively and efficiently, so it can be expected to facilitate better public participation in the fight against COVID-19.",2020,"Gao, Peichao; Zhang, Hong; Wu, Zhiwei; Wang, Jicheng",Environment and Planning A: Economy and Space,3006007867,#2287,
,CZI,CT Imaging and Differential Diagnosis of COVID-19,10.1177/0846537120913033,,,,"Since the beginning of 2020, coronavirus disease 2019 (COVID-19) has spread throughout China. This study explains the findings from lung computed tomography images of some patients with COVID-19 treated in this medical institution and discusses the difference between COVID-19 and other lung diseases.",2020,"Dai, Wei-cai; Zhang, Han-wen; Yu, Juan; Xu, Hua-jian; Chen, Huan; Luo, Si-ping; Zhang, Hong; Liang, Li-hong; Wu, Xiao-liu; Lei, Yi; Lin, Fan",Canadian Association of Radiologists Journal,2605750182,#4047,
,CZI,COVID-19: What Can We Learn From Stories From the Trenches?,10.1177/0846537120913497,,,,"A few reports have been published recently highlighting the role of chest computed tomography (CT) in diagnosis of COVID-19.2-4 Chest CT demonstrates a high sensitivity in patients with COVID-19. The CT imaging findings in COVID-19 are similar to features of other viral pneumonias and familiar to imagers.2-4 The speed of acquisition of CT and timely reporting by radiologists will help our ED colleagues to make a diagnosis of COVID-19 within minutes, not hours or days. Nevertheless, this outbreak raises important clinical questions relevant to radiological community.",2020,"Patlas, Michael N.",Canadian Association of Radiologists Journal,2248885652,#3889,
,CZI,The 2019-nCoV epidemic control strategies and future challenges of building healthy smart cities,10.1177/1420326X20910408,,,,"reported and confirmed on 31 December 2019, in Wuhan, Hubei Province, China, which is one of China’s largest cities and a major domestic transport hub (located in the central part of China, as shown in Figure 1).1 The epidemic is attracting worldwide concern due to its rapid spread and transmission rate between humans. On 30 January 2020, the International Health Regulations, Emergency Committee of the World Health Organization (WHO) declared the outbreak – a ‘public health emergency of international concern’.2 On 8 February 2020 (24:00 GMT?+?8), there were 37,198 confirmed infections in China (including 811 deaths with a death ratio of 2.1%; and 6188 patients were confirmed in serious condition and 28,942 suspected cases).3 The COVID 19 infections were also reported in 26 other countries on 7 February 2020, including Canada, the USA, Australia, India, Sri-Lanka, Cambodia, Thailand, Vietnam, Malaysia, Singapore, Taiwan, the Republic of Korea, Sri Lanka, Japan, Philippines, Nepal, United Arab Emirates, Russia, Italy, Germany, Sweden, Finland, Belgium, Spain, France and the UK.4",2020,"Xu, Chunwen; Luo, Xilian; Yu, Chuck; Cao, Shi-Jie",Indoor and Built Environment,1987841849,#3268,
,CZI,Key points for the prevention and treatment of the novel coronavirus pneumonia in the elderly,10.1177/1938640016668030,,,,"The population is commonly susceptible to the 2019 novel coronavirus(2019-nCoV), especially the elderly with comorbidities.Elderly patients infected with 2019-nCoV tend to have higher rates of severe illnesses and mortality.Immunoaging is an important cause of severe novel coronavirus pneumonia(NCP)in the elderly.Due to the combination of underlying diseases, elderly patients may exhibit a typical manifestations in clinical symptoms, supplementary examinations and pulmonary imaging, deserving particular attention.The general condition of the elderly should be considered during diagnosis and treatment.In addition to routine care and measures such as oxygen therapy, antiviral therapy and respiratory support, treatment of underlying disease, nutritional support, sputum expectoration, complication prevention and psychological support should also be considered for elderly patients.Based on literature review and expert panel discussion, we drafted the Key Points for the Prevention and Treatment of the Novel Coronavirus Pneumonia in the elderly, aiming to provide help with the prevention and treatment of NCP and the reduction of harm to the elderly population.",2020,"CHEN, Qiong; YU, Weiwei; WANG, Lijing; XI, Huan; ZHANG, Qiang; CHEN, Xinyu; HUANG, Kui; LU, Xiang; LIU, Xinmin; ZHANG, Cuntai; WANG, Jianye",Chinese Journal of Geriatrics,2511525332,#2335,
,CZI,"Epidemiological characteristics of 2019-ncoV infections in Shaanxi, China by February 8, 2020",10.1183/13993003.00310-2020,,32139462,,,2020,"Yao, Y.; Tian, Y.; Zhou, J.; Ma, X.; Yang, M.; Wang, S.",The European respiratory journal,3006299216,#5374,
,CZI,"The clinical dynamics of 18 cases of COVID-19 outside of Wuhan, China",10.1183/13993003.00398-2020,,32139464,,,2020,"Wang, L.; Gao, Y. H.; Lou, L. L.; Zhang, G. J.",The European respiratory journal,2613706279,#5274,
,CZI,Q&A: The novel coronavirus outbreak causing COVID-19 A mathematical model for simulating the phase-based transmissibility of a novel coronavirus,10.1186/s12916-020-01533-w 10.1186/s40249-020-00640-3,,,,"The virus responsible for COVID-19, SARS-CoV-2, is in the species SARS-like corona viruses. At 125?nm, it is slightly larger than influenza, SARS and MERS viruses. It is almost certainly a descendant from a bat corona virus of which there are many. The closest is a virus that originated from the Rhinolophus bat which is >?96% homologous with the current SARS-CoV-2 virus. It is only 79% homologous with the original SARS CoV [1].ID - Fisher2020 As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. The virus was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by International Committee on Taxonomy of Viruses on 11 February, 2020. This study aimed to develop a mathematical model for calculating the transmissibility of the virus.",2020,"Fisher, Dale; Heymann, David; Chen, Tian-Mu; Rui, Jia; Wang, Qiu-Peng; Zhao, Ze-Yu; Cui, Jing-An; Yin, Ling",BMC Medicine,,#2645,
,CZI,Expert consensus on elderly patients with hip fracture under epidemic of novel coronavirus pneumonia,10.1186/s13104-015-1129-5,,,,"With the spread of novel coronavirus pneumonia (NCP) in December 2019, the management and rehabilitation of elderly patients with hip fractures and protection of medical staff face new challenges, and need to be adjusted appropriately under this very circumstances. Hip fractures in the elderly account for more than half of osteoporotic fractures. Expert group formulate this consensus so as to make better decision against this epidemic and protect patients' families and medical staff. This consensus elaborates not only epidemic condition of NCP, but also general principles of medical admission, treatment and protection for both medical staff and patients, in order to provide some reference and promote the standardization of clinical diagnosis and treatment of elderly patients with hip fractures under the condition of NCP.",2020,"LIU, Guohui; LIU, Ximing; TONG, Xiaoling; WANG, Dongliang; CHEN, Yanxi; CAO, Liehu; LIU, Guodong; LIU, Jing; HU, Yan; HUANG, Biaotong; SHI, Zhongmin; ZHANG, Dianying; HOU, Zhiyong; LIU, Hongjian; TONG, Peijian; SONG, Shaojun; YANG, Lei; WANG, Yong; ZHANG, Lei; LUO, Tao; WANG, Meitang; ZHANG, Peng; ZHANG, Yong; LIN, Haodong; YU, Baoqing; MI, Bobin; ZHANG, Yingze; SU, Jiacan",Chinese Journal of Trauma,2106264008,#2188,
,CZI,Current status of treatment for 2019 novel coronavirus pneumonia,10.1186/s40779-020-0233-6,,,,"2019 novel coronavirus (2019-nCoV) is a new member of coronavirus family that can cause serious respiratory diseases after the emergence of severe acute respiratory syndrome-coronavirus (SARS-CoV) and middle east respiratory syndrome-coronavirus (MERS-CoV). At present, there is no specific antiviral drug targeting 2019-nCoV. In facing of the increasingly serious epidemic of 2019 novel coronavirus pneumonia and the urgent needs in drug treatment strategies, this paper reviewed the current research situation and progress in antiviral treatment for the newly identified disease.",2020,"ZHU, Naiwei; ZHAO, Ping; QI, Zhongtian",Chinese Journal of Microbiology and Immunology,3004824173,#2040,
,CZI,Treatment of 2019 novel coronavirus pneumonia based on the theory of 'three syndromes and three methods',10.1186/s40779-020-0233-6,,,,"The latest diagnosis and treatment plan (4th edition) of 2019 novel coronavirus pneumonia has been issued. The diagnosis and treatment plan highlights the concept of integrated traditional Chinese and Western medicine, and Xuebijing injection was referred for three times. Xuebijing injection was successfully developed based on the theory of 'three syndromes and three methods'. The theory of 'three syndromes and three methods' is a theoretical system of integrated traditional Chinese and Western medicine on critical diseases proposed by Professor Wang Jinda and his team in the 1970s, and it is one of the main contents of Wang Jinda's academic thought. The theory of 'three syndromes and three methods' has a deep foundation of traditional Chinese medicine theory, and it is still being continuously enriched and improved. It is also supported by multiple evidence-based data. Therefore, 'three syndromes and three methods' has rich theoretical connotation and tenacious vitality.",2020,"LI, Zhijun; LI, Yinping; WANG, Bochao",Chinese Critical Care Medicine,3004824173,#2198,
,CZI,Coronavirus disease-2019: is fever an adequate screening for the returning travelers?,10.1186/s41182-020-00201-2,,,,"On Thursday, 30 January 2020, World Health Organization declared Coronavirus disease-2019 (COVID-2019) a Public Health Emergency of International Concern. Since its identification in late December 2019 in Wuhan, Hubei Province, People’s Republic of China, the number of cases imported into other countries is increasing, and the epidemiological map is changing rapidly. On the other hand, body temperature screening (fever) is the major test performed at points of entry, i.e., airports, in the returning travelers in most of the countries with limited resources. However, the recent report on asymptomatic contact transmission of COVID-19 and travelers who passed the symptoms-based screening and tested positive for COVID-19 using reverse transcription polymerase chain reaction (RT-PCR) challenges this approach as body temperature screening may miss travelers incubating the disease or travelers concealing fever during travel. On this note, travel restrictions to and from high risk areas and/or 14 days quarantine of travelers coming from high risk areas are recommended to prevent possible importation of COVID-19. Currently, RT-PCR is a reliable test in detecting both symptomatic and asymptomatic COVID-19.",2020,"Bwire, George M.; Paulo, Linda S.",Tropical Medicine and Health,2145339500,#5077,
,CZI,"The novel coronavirus outbreak in Wuhan, China Development and validation of knowledge, attitude and practice questionnaire for prevention of respiratory tract infections among Malaysian Hajj pilgrims",10.1186/s41256-020-00135-6 10.1186/s12889-020-8269-9,,,,"The novel coronavirus (2019-nCoV, or COVID-19) epidemic first broke out in Wuhan and has been spreading in whole China and the world. The numbers of new infections and deaths in Wuhan are still increasing, which have posed major public health and governance concerns. A series of mandatory actions have been taken by the municipal and provincial governments supported by the central government, such as measures to restrict travels across cities, case detection and contact tracing, quarantine, guidance and information to the public, detection kit development, etc. Challenges such as lacking effective drugs, insufficient hospital services and medical supplies, logistics, etc. have much alleviated with the solidarity of the whole society. The pandemic will definitely be ended with the continuous efforts of both national and international multi-sectoral bodies. Hajj pilgrimage faces numerous challenges including a high prevalence of respiratory tract infection as well as its prevention strategies. The aim of this study was to develop and validate a questionnaire to evaluate knowledge, attitude and practice (KAP) towards respiratory tract infections (RTIs) prevention among Malaysian Hajj pilgrims.",2020,"Zhu, Hengbo; Wei, Li; Niu, Ping; Goni, Mohammed Dauda; Naing, Nyi Nyi; Hasan, Habsah; Wan-Arfah, Nadiah; Deris, Zakuan Zainy; Arifin, Wan Nor; Hussin, Tengku Mohammad Ariff Raja; Abdulrahman, Abdulwali Sabo; Baaba, Aisha Abubakar; Arshad, Muhammad Rafie",Global Health Research and Policy,2999409984,#3234,
,CZI,The novel coronavirus outbreak: what can be learned from China in public reporting?,10.1186/s41256-020-00140-9,,,,"The new coronavirus outbreak gets everyone’s attention. China’s national actions against the outbreak have contributed great contributions to the world. China has been learning from practice for better reporting and is fast to adapt itself. In this article we discuss China’s practice in public reporting and its implications to global health. Confirmed cases, dynamic suspected cases, recovered cases, and deaths have been reported both in accumulative numbers and their daily updates. Some ratio indictors reporting (fatality rate, recovery rate, etc.), trend reporting, and global surveillance have been applied as well. Some improvements can still be made. It is necessary to further explore the influential factors behind the indicators for interventions. Recommendations are made to the World Health Organization and other countries for better public reporting and surveillance.",2020,"Li, Hao; Chen, Xinguang; Huang, Hao",Global Health Research and Policy,3003668884,#4808,
,CZI,Clinical features and high resolutionCT imaging findings of preliminary diagnosis novel coronavirus pneumonia,10.1200/jco.2014.32.15_suppl.11000,,,,"Objective To summarize the clinical characteristics of 141 patients with novel coronavirus pneumonia (NCP) and the imaging characteristics of High Resolution CT(HRCT) in the chest. Methods From January 20, 2020 to 28, 141 NCP patients, 77 males and 64 females, with a median age of 49 (9,87), were retrospectively analyzed. The clinical features, laboratory examination indexes and HRCT findings of 141 NCP patients were analyzed. Results In 141 NCP patients, 38 (26.95%) had a decrease in leukocyte count and 71 (50.35%) had a decrease in lymphocyte ratio. Among 141 NCP patients, 139 (98.58%) had fever (over 37.5 &deg; C), 106 (75.18%) coughed, 11 (7.80%) had headache, 41 (29.08%) coughed up sputum, 93 (65.96%) had chest distress, and 4 (2.84%) had diarrhea. HRCT of 141 NCP patients were abnormal, 52 (36.88%) showed ground glass shadow (GGO) and patchy shadow, mainly subpleural distribution; 23 (16.31%) showed GGO with focal consolidation; 27 (19.15%) had small patchy blur; 20 (14.18%) had large patchy consolidation; 48 (34.04%) had bronchovascular bundle thickening and vascular perforator sign; 5 (3.55%) had Air bronchus sign; small nodule shadow in 7 cases (4.96%); fibrosis, grid shadow or strip shadow in 5 cases (3.55%); bilateral pleural effusion in 7 cases (4.96%); mediastinal or bilateral hilar lymphadenopathy in 4 cases (2.84%). Conclusions The clinical features and HRCT images of NCP are various. Under the specific epidemiological background of NCP, HRCT scan of chest should be carried out in time to make early warning of disease.",2020,"LU, Xuefang; GONG, Wei; WANG, Li; LI, Liang; XIE, Baojun; PENG, Zhoufeng; ZHA, Yunfei",Chinese Journal of Radiology,2907998690,#2179,
,CZI,Novel coronavirus (SARS-CoV-2) epidemic: a veterinary perspective,10.12834/VetIt.1768.9338.1,,32048818,,,2020,"Lorusso, Alessio; Calistri, Paolo; Petrini, Antonio; Savini, Giovanni; Decaro, Nicola",Vet Ital,3005538648,#754,
,CZI,Novel coronavirus (COVID‑19) epidemic: a veterinary perspective,10.12834/VetIt.2173.11599.1,,,,,2020,"Lorusso, A.; Calistri, P.; Petrini, A.; Savini, G.; Decaro, N.",Veterinaria italiana,,#1559,
,CZI,Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic,10.12932/ap-200220-0772,,32105090,,"As the world is witnessing the epidemic of COVID-19, a disease caused by a novel coronavirus, SARS-CoV-2, emerging genetics and clinical evidences suggest a similar path to those of SARS and MERS. The rapid genomic sequencing and open access data, together with advanced vaccine technology, are expected to give us more knowledge on the pathogen itself, including the host immune response as well as the plan for therapeutic vaccines in the near future. This review aims to provide a comparative view among SARS-CoV, MERS-CoV and the newly epidemic SARS-CoV-2, in the hope to gain a better understanding of the host-pathogen interaction, host immune responses, and the pathogen immune evasion strategies. This predictive view may help in designing an immune intervention or preventive vaccine for COVID-19 in the near future.",2020,"Prompetchara, E.; Ketloy, C.; Palaga, T.",Asian Pacific journal of allergy and immunology,2777011210,#2922,
,CZI,Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19),10.12932/ap-200220-0773,,32134278,,"Last decade witnessed the outbreak of many life-threatening human pathogens including Nipah, Ebola, Chikungunya, Zika, Middle East respiratory syndrome coronavirus (MERS-CoV), Severe Acute respiratory syndrome coronavirus (SARS-CoV) and more recently novel coronavirus (2019-nCoV or SARS-CoV-2). The disease condition associated with novel coronavirus, referred to as Coronavirus disease (COVID-19). The emergence of novel coronavirus in 2019 in Wuhan, China marked the third highly pathogenic coronavirus infecting humans in the 21st century. The continuing emergence of coronaviruses at regular intervals poses a significant threat to human health and economy. Ironically, even after a decade of research on coronavirus, still there are no licensed vaccines or therapeutic agents to treat coronavirus infection which highlights an urgent need to develop effective vaccines or post-exposure prophylaxis to prevent future epidemics. Several clinical, genetic and epidemiological features of COVID-19 resemble SARS-CoV infection. Hence, the research advancements on SARS-CoV treatment might help scientific community in quick understanding of this virus pathogenesis and develop effective therapeutic/prophylactic agents to treat and prevent this infection. Monoclonal antibodies represent the major class of biotherapeutics for passive immunotherapy to fight against viral infection. The therapeutic potential of monoclonal antibodies has been well recognized in the treatment of many diseases. Here, we summarize the potential monoclonal antibody based therapeutic intervention for COVID-19 by considering the existing knowledge on the neutralizing monoclonal antibodies against similar coronaviruses SARS-CoV and MERS-CoV. Further research on COVID-19 pathogenesis could identify appropriate therapeutic targets to develop specific anti-virals against this newly emerging pathogen.",2020,"Shanmugaraj, B.; Siriwattananon, K.; Wangkanont, K.; Phoolcharoen, W.",Asian Pacific journal of allergy and immunology,1633890482,#5213,
,CZI,"Infections without borders: a new coronavirus in Wuhan, China",10.12968/bjon.2020.29.3.166,,32053437,,,2020,"Wood, Cate",Br J Nurs,3006148298,#875,
,CZI,"Brief review of coronavirus for healthcare professionals February 10, 2020",10.13175/swjpcc011-20,,,,"A novel epidemic is challenging the global health care system. Starting from probably November to December 2019, another Coronavirus entered the arena of human pathogens, to be then defined 2019- nCoV [...].",2020,"SA, Robbins RA; Klotz",Southwest Journal of Pulmonary and Critical Care. 2020;20(2):69-70,3006453194,#695,
,CZI,Two clinical cases of Novel coronavirus pneumonia (NCP) in renal transplant recipients,10.1371/journal.pone.0164320,,,,"Objective To explore the clinical features, diagnosis and prognosis of renal transplant recipients with NCP. Method The clinical data of 2 cases of kidney transplant recipients with NCP were retrospectively analyzed. Based onclinical manifestations, blood routine, inflammatory factors, cell immunity, chest CT andtherapeutic effects, the diagnosis and treatment of NCP in kidney transplant recipients (5th edition) were compared to that ofordinary NCP patients. Both recipients developed onset of low andmoderate fever, with no cough or fatigue at the initial stage. Blood routine indicated a normal range of leukocytes,buta significant decrease in lymphocyte counts, increased C-reactive protein (CRP) , and slightly higher procalcitonin (PCT) . The cellular immunity was extremely low, and the chest CT showed multiple patchy ground glass shadows in both lungs. Result After 1 week of onset, both patients had significant disease progression. The pathogenesis and imaging changes were highly similar tothatreported in ordinary NCP patients.Two patients were givensymptomatic supportive treatment by antiviral agents, stop uses ofimmunosuppression agents, small amount of hormone maintenance, intravenous drip of gamma globulin andrespiratory support toavoid secondary infections. At present, the condition of both patients is obviously improved, and renal function is stable. One of them has recovered and was discharged. Conclusion The clinical manifestations of NCP in renal transplant recipients were generally consistent with that of ordinary NCP patients. Although there is no established method for the treatment of NCP, it is effective by stopping uses of immunosuppressive agents, maintaining small and medium doses of hormones, actively restoring immunity, and providing respiratory support in a timely manner.",2020,"TU, Yafang; WU, Xiongfei; LIU, Feng; WANG, Juan; LUO, Yu; CAI, Zhitao; CHEN, Rengui; LIAO, Wenliang; LIU, Na; HUANG, Jin",Chinese Journal of Organ Transplantation,2556328182,#2140,
,CZI,"Communication, transparency key as Canada faces new coronavirus threat",10.1503/cmaj.1095846,,32071113,,,2020,"Glauser, Wendy",CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne,1953687642,#4117,
,CZI,What can early Canadian experience screening for COVID-19 teach us about how to prepare for a pandemic?,10.1503/cmaj.200305,,32144097,,,2020,"Lin, M.; Beliavsky, A.; Katz, K.; Powis, J. E.; Ng, W.; Williams, V.; Science, M.; Groves, H.; Muller, M. P.; Vaisman, A.; Hota, S.; Johnstone, J.; Leis, J. A.",CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne,2482414787,#4856,
,CZI,Laboratory abnormalities in patients with COVID-2019 infection,10.1515/cclm-2020-0198,,32119647,,,2020,"Lippi, Giuseppe; Plebani, Mario",Clin Chem Lab Med,2996021282,#3347,
,CZI,The novel coronavirus (2019-nCoV) outbreak: Think the unthinkable and be prepared to face the challenge,10.1515/dx-2020-0015,,,,,2020,"Lippi, G.; Plebani, M.",Diagnosis,3003218364,#758,
,CZI,"Initial Public Health Response and Interim Clinical Guidance for the 2019 Novel Coronavirus Outbreak - United States, December 31, 2019-February 4, 2020",10.15585/mmwr.mm6905e1,,32027631,,"On December 31, 2019, Chinese health officials reported a cluster of cases of acute respiratory illness in persons associated with the Hunan seafood and animal market in the city of Wuhan, Hubei Province, in central China. On January 7, 2020, Chinese health officials confirmed that a novel coronavirus (2019-nCoV) was associated with this initial cluster (1). As of February 4, 2020, a total of 20,471 confirmed cases, including 2,788 (13.6%) with severe illness,* and 425 deaths (2.1%) had been reported by the National Health Commission of China (2). Cases have also been reported in 26 locations outside of mainland China, including documentation of some person-to-person transmission and one death (2). As of February 4, 11 cases had been reported in the United States. On January 30, the World Health Organization (WHO) Director-General declared that the 2019-nCoV outbreak constitutes a Public Health Emergency of International Concern.(†) On January 31, the U.S. Department of Health and Human Services (HHS) Secretary declared a U.S. public health emergency to respond to 2019-nCoV.(§) Also on January 31, the president of the United States signed a ""Proclamation on Suspension of Entry as Immigrants and Nonimmigrants of Persons who Pose a Risk of Transmitting 2019 Novel Coronavirus,"" which limits entry into the United States of persons who traveled to mainland China to U.S. citizens and lawful permanent residents and their families (3). CDC, multiple other federal agencies, state and local health departments, and other partners are implementing aggressive measures to slow transmission of 2019-nCoV in the United States (4,5). These measures require the identification of cases and their contacts in the United States and the appropriate assessment and care of travelers arriving from mainland China to the United States. These measures are being implemented in anticipation of additional 2019-nCoV cases in the United States. Although these measures might not prevent the eventual establishment of ongoing, widespread transmission of the virus in the United States, they are being implemented to 1) slow the spread of illness; 2) provide time to better prepare health care systems and the general public to be ready if widespread transmission with substantial associated illness occurs; and 3) better characterize 2019-nCoV infection to guide public health recommendations and the development of medical countermeasures including diagnostics, therapeutics, and vaccines. Public health authorities are monitoring the situation closely. As more is learned about this novel virus and this outbreak, CDC will rapidly incorporate new knowledge into guidance for action by CDC and state and local health departments.",2020,"Patel, Anita; Jernigan, Daniel B.; nCo, V. C. D. C. Response Team",MMWR Morb Mortal Wkly Rep,3004775012,#454,
,CZI,"Erratum: Vol. 69, No. 5",10.15585/mmwr.mm6906a5,,32053580,,,2020,"nCo, V. C. D. C. Response Team",MMWR Morb Mortal Wkly Rep,2329951566,#829,
,CZI,"Persons Evaluated for 2019 Novel Coronavirus - United States, January 2020",10.15585/mmwr.mm6906e1,,32053579,,"In December 2019, a cluster of cases of pneumonia emerged in Wuhan City in central China's Hubei Province. Genetic sequencing of isolates obtained from patients with pneumonia identified a novel coronavirus (2019-nCoV) as the etiology (1). As of February 4, 2020, approximately 20,000 confirmed cases had been identified in China and an additional 159 confirmed cases in 23 other countries, including 11 in the United States (2,3). On January 17, CDC and the U.S. Department of Homeland Security's Customs and Border Protection began health screenings at U.S. airports to identify ill travelers returning from Wuhan City (4). CDC activated its Emergency Operations Center on January 21 and formalized a process for inquiries regarding persons suspected of having 2019-nCoV infection (2). As of January 31, 2020, CDC had responded to clinical inquiries from public health officials and health care providers to assist in evaluating approximately 650 persons thought to be at risk for 2019-nCoV infection. Guided by CDC criteria for the evaluation of persons under investigation (PUIs) (5), 210 symptomatic persons were tested for 2019-nCoV; among these persons, 148 (70%) had travel-related risk only, 42 (20%) had close contact with an ill laboratory-confirmed 2019-nCoV patient or PUI, and 18 (9%) had both travel- and contact-related risks. Eleven of these persons had laboratory-confirmed 2019-nCoV infection. Recognizing persons at risk for 2019-nCoV is critical to identifying cases and preventing further transmission. Health care providers should remain vigilant and adhere to recommended infection prevention and control practices when evaluating patients for possible 2019-nCoV infection (6). Providers should consult with their local and state health departments when assessing not only ill travelers from 2019-nCoV-affected countries but also ill persons who have been in close contact with patients with laboratory-confirmed 2019-nCoV infection in the United States.",2020,"Bajema, Kristina L.; Oster, Alexandra M.; McGovern, Olivia L.; Lindstrom, Stephen; Stenger, Mark R.; Anderson, Tara C.; Isenhour, Cheryl; Clarke, Kevin R.; Evans, Mary E.; Chu, Victoria T.; Biggs, Holly M.; Kirking, Hannah L.; Gerber, Susan I.; Hall, Aron J.; Fry, Alicia M.; Oliver, Sara E.; nCo, V. Persons Under Investigation Team; Co, V. Persons Under Investigation Team",MMWR Morb Mortal Wkly Rep,3004490697,#830,
,CZI,"Update: Public Health Response to the Coronavirus Disease 2019 Outbreak - United States, February 24, 2020",10.15585/mmwr.mm6908e1,,32106216,,"An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in Wuhan, Hubei Province, China in December 2019, and has spread throughout China and to 31 other countries and territories, including the United States (1). As of February 23, 2020, there were 76,936 reported cases in mainland China and 1,875 cases in locations outside mainland China (1). There have been 2,462 associated deaths worldwide; no deaths have been reported in the United States. Fourteen cases have been diagnosed in the United States, and an additional 39 cases have occurred among repatriated persons from high-risk settings, for a current total of 53 cases within the United States. This report summarizes the aggressive measures (2,3) that CDC, state and local health departments, multiple other federal agencies, and other partners are implementing to slow and try to contain transmission of COVID-19 in the United States. These measures require the identification of cases and contacts of persons with COVID-19 in the United States and the recommended assessment, monitoring, and care of travelers arriving from areas with substantial COVID-19 transmission. Although these measures might not prevent widespread transmission of the virus in the United States, they are being implemented to 1) slow the spread of illness; 2) provide time to better prepare state and local health departments, health care systems, businesses, educational organizations, and the general public in the event that widespread transmission occurs; and 3) better characterize COVID-19 to guide public health recommendations and the development and deployment of medical countermeasures, including diagnostics, therapeutics, and vaccines. U.S. public health authorities are monitoring the situation closely, and CDC is coordinating efforts with the World Health Organization (WHO) and other global partners. Interim guidance is available at https://www.cdc.gov/coronavirus/index.html. As more is learned about this novel virus and this outbreak, CDC will rapidly incorporate new knowledge into guidance for action by CDC, state and local health departments, health care providers, and communities.",2020,"Jernigan, D. B.",MMWR. Morbidity and mortality weekly report,3004775012,#2845,
,CZI,"Active Monitoring of Persons Exposed to Patients with Confirmed COVID-19 — United States, January–February 2020",10.15585/mmwr.mm6909e1external,,,,"In December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, began in Wuhan, China (1). The disease spread widely in China, and, as of February 26, 2020, COVID-19 cases had been identified in 36 other countries and territories, including the United States. Person-to-person transmission has been widely documented, and a limited number of countries have reported sustained person-to-person spread.* On January 20, state and local health departments in the United States, in collaboration with teams deployed from CDC, began identifying and monitoring all persons considered to have had close contact† with patients with confirmed COVID-19 (2). The aims of these efforts were to ensure rapid evaluation and care of patients, limit further transmission, and better understand risk factors for transmission.",2020,"Sara Rudman; Sarah Scott; Aron J. Hall Alicia M. Fry; Melissa A. Rolfes, Rachel M. Burke; Claire M. Midgley; Alissa Dratch; Marty Fenstersheib; Thomas Haupt; Michelle Holshue; Isaac Ghinai; M. Claire Jarashow; Jennifer Lo; Tristan D. McPherson;",MMWR and Morbidity and Mortality Weekly Report,,#3308,
,CZI,The 2019 novel coronavirus resource,10.16288/j.yczz.20-030,,32102777,,"An ongoing outbreak of a novel coronavirus infection in Wuhan, China since December 2019 has led to 31,516 infected persons and 638 deaths across 25 countries (till 16:00 on February 7, 2020). The virus causing this pneumonia was then named as the 2019 novel coronavirus (2019-nCoV) by the World Health Organization. To promote the data sharing and make all relevant information of 2019-nCoV publicly available, we construct the 2019 Novel Coronavirus Resource (2019nCoVR, https://bigd.big.ac.cn/ncov). 2019nCoVR features comprehensive integration of genomic and proteomic sequences as well as their metadata information from the Global Initiative on Sharing All Influenza Data, National Center for Biotechnology Information, China National GeneBank, National Microbiology Data Center and China National Center for Bioinformation (CNCB)/National Genomics Data Center (NGDC). It also incorporates a wide range of relevant information including scientific literatures, news, and popular articles for science dissemination, and provides visualization functionalities for genome variation analysis results based on all collected 2019-nCoV strains. Moreover, by linking seamlessly with related databases in CNCB/NGDC, 2019nCoVR offers virus data submission and sharing services for raw sequence reads and assembled sequences. In this report, we provide comprehensive descriptions on data deposition, management, release and utility in 2019nCoVR, laying important foundations in aid of studies on virus classification and origin, genome variation and evolution, fast detection, drug development and pneumonia precision prevention and therapy.",2020,"Zhao, W. M.; Song, S. H.; Chen, M. L.; Zou, D.; Ma, L. N.; Ma, Y. K.; Li, R. J.; Hao, L. L.; Li, C. P.; Tian, D. M.; Tang, B. X.; Wang, Y. Q.; Zhu, J. W.; Chen, H. X.; Zhang, Z.; Xue, Y. B.; Bao, Y. M.",Yi chuan = Hereditas,2916654259,#3031,
,CZI,How to conduct clinical research on anesthesiology during epidemic of the novel coronavirus pneumonia: recommendations from the epidemiological perspective,10.17226/10958,,,,"During the outbreak and epidemic of novel coronavirus pneumonia, anesthesiologists are not only the high-risk group of secondary infection, but also undertake tasks to initiate clinical research so that the regular pattern of disease could be summarized, which will product clinical evidences for clinical decision-making and optimization of anesthesia therapy as soon as possible. The clinical research evidences of anaesthesia are of great importance for improving the prevention and control strategy of infectious diseases and implementing relevant measures effectively. The recommendations from the epidemiological perspective are provided on how to conduct clinical research on anesthesiology during epidemic of the novel coronavirus pneumonia in the present paper: (1) The case report and case series research should be initiated promptly once the infectious cases treated in anesthesia department are diagnosed; (2) To focus on need of evidence of decision-making of diagnosis and treatment, to summarize general rules timely and to promote the rapidly production of evidence; (3) To establish a special cohort of novel coronavirus pneumonia so that more prognosis studies could be carried out; (4) To explore the risk factors which result in hospital infection among medical staffs so that hospital infection could be controlled. The purpose of this study is to provide clinicians with methodological suggestions on how to carry out high-quality clinical research in the epidemic period of infectious diseases, and to close the gap between clinical and public health.",2020,"PENG, Xiaoxia; LI, Nan",Chinese Journal of Anesthesiology,1600391151,#2150,
,CZI,COVID-19. The only certainty is the uncertainty,10.17992/lbl.2020.03.469,,32124733,,,2020,"Briem, Haraldur",Laeknabladid,3006338236,#3453,
,CZI,Effects and challenges of Open Science - Academic movements related to the Novel coronavirus (2019-nCoV) and COVID-19,10.18919/jkg.70.3_140,,,,オープンサイエンスの効果はさまざまに論じられてき た。たとえば経済協力開発機構（OECD）の報告書 1) では， 科学研究の効率化，研究の透明性や質の向上，技術革新の 加速，経済への波及効果，地球規模の課題への取り組み， 共同研究の推進などが挙げられている。 折しも 2019 年 12 月以降，新型コロナウイルス（2019- nCoV）の感染が中国の武漢市から世界中に拡大して「地 球規模の課題」となっている。2020 年 1 月 30 日には世 界保健機関（WHO）が国際的な緊急事態であると宣言し た 2)。これに対して各国・地域の研究者，助成機関，学術 出版社といったステークホルダーが最新の研究成果の公開 と再利用を進めて対策にあたるという，まさに「オープン サイエンス」というべき動きが起きている。そこで本稿は 新型コロナウイルスに関する学術界の動向を概観した上 で，今回の事例におけるオープンサイエンスの効果と課題 について考察したい。なお，本稿の記述は 2020 年 2 月 6 日時点の情報に基づいている（情報が古い箇所もあろうか と思いますが，ご容赦を）。,2020,,The Journal of Information Science and Technology Association,871210397,#3003,
,CZI,"The 2019 Novel Coronavirus (2019-nCoV): Novel Virus, Old Challenges",10.20344/amp.13547,,32023427,,,2020,"Duarte, Raquel; Furtado, Isabel; Sousa, Luís; Carvalho, Carlos Filipe Afonso",Acta Med Port,3004691782,#327,
,CZI,Fighting the novel coronavirus: the publication of the Chinese expert consensus on the perinatal and neonatal management for the prevention and control of the 2019 novel coronavirus infection (First edition),10.21037/apm.2020.02.02,,32028773,,,2020,"Editorial, Office",Ann Palliat Med,3004450134,#550,
,CZI,Which lessons shall we learn from the 2019 novel coronavirus outbreak?,10.21037/atm.2020.02.06,,,,,2020,"Mattiuzzi, Camilla; Lippi, Giuseppe",Annals of Translational Medicine,3005487212,#3833,
,CZI,Perinatal and neonatal management plan for prevention and control of 2019 novel coronavirus infection (1st Edition),10.21037/atm.2020.02.20,,32051071,,"Since December 2019, the novel coronavirus (2019-nCoV) infection has been prevalent in China. Due to immaturity of immune function and the possibility of mother-fetal vertical transmission, neonates are particularly susceptible to 2019-nCoV. The perinatal-neonatal departments should cooperate closely and take integrated approaches, and the neonatal intensive care unit should prepare the emergency plan for 2019-nCoV infection as far as possible, so as to ensure the optimal management and treatment of potential victims. According to the latest 2019-nCoV national management plan and the actual situation, the Working Group for the Prevention and Control of Neonatal 2019-nCoV Infection in the Perinatal Period of the Editorial Committee of Chinese Journal of Contemporary Pediatrics puts forward recommendations for the prevention and control of 2019-nCoV infection in neonates.",2020,"Working Group for the, Prevention; Control of Neonatal -nCo, V. Infection in the Perinatal Period of the Editorial Committee of Chinese Journal of Contemporary Pediatrics",Zhongguo Dang Dai Er Ke Za Zhi,3004450134,#810,
,CZI,Management plan for prevention and control of novel coronavirus pneumonia among children in Xiangya Hospital of Central South University,10.21037/atm.2020.02.20,,32051074,,"Since December 2019, an epidemic of novel coronavirus pneumonia (NCP) has occurred in China. How to effectively prevent and control NCP among children with limited resources is an urgent issue to be explored. Under the unified arrangement of the Xiangya Hospital of Central South University, the Department of Pediatrics has formulated an action plan with Xiangya unique model to prevent and control NCP among children according to the current epidemic situation and diagnostic and therapeutic program in China.",2020,"Peng, Jing; Wang, Xia; Yang, Ming-Hua; Wang, Ming-Jie; Zheng, Xiang-Rong",Zhongguo Dang Dai Er Ke Za Zhi,3004450134,#811,
,CZI,Chinese expert consensus on the perinatal and neonatal management for the prevention and control of the 2019 novel coronavirus infection (First edition),10.21037/atm.2020.02.20,,,,"Since December 2019, there has been an outbreak of novel coronavirus (2019-nCoV) infection in China. Two cases of neonates with positive 2019-nCoV tests have been reported. Due to the immature immune system and the possibility of vertical transmission from mother to infant, neonates have become a high-risk group susceptible to 2019-nCoV, which emphasize a close cooperation from both perinatal and neonatal pediatrics. In neonatal intensive care unit (NICU), to prevent and control infection, there should be practical measures to ensure the optimal management of children potentially to be infected. According to the latest 2019-nCoV national management plan and the actual situation, the Chinese Neonatal 2019-nCoV expert working Group has put forward measures on the prevention and control of neonatal 2019-nCoV infection.",2020,"Wang, Laishuan; Shi, Yuan; Xiao, Tiantian; Fu, Jianhua; Feng, Xing; Mu, Dezhi; Feng, Qi; Hei, Mingyan; Hu, Xiaojing; Li, Zhankui; Lu, Guoping; Tang, Zezhong; Wang, Yajuan; Wang, Chuanqing; Xia, Shiwen; Xu, Jianqing; Yang, Yujia; Yang, Jie; Zeng, Mei; Zheng, Jun; Zhou, Wei; Zhou, Xiaoyu; Zhou, Xiaoguang; Du, Lizhong; Lee, Shoo K.; Zhou, Wenhao; Working Comm Perinatal, Neona",Annals of Translational Medicine,3004450134,#4170,
,CZI,Straining the System: Novel Coronavirus (COVID-19) and Preparedness for Concomitant Disasters,10.2105/AJPH.2020.305618,,32053389,,"Just a few weeks before the first confirmed case of novel coronavirus (COVID-19) was reported in the United States, the US Centers for Disease Control and Prevention (CDC) issued a bold promise to the nation: the agency will use its scientific expertise to bring a new level of preparedness in the United States and global health security against current and growing threats, finally eliminate certain diseases, and bring an end to the devastation of epidemics.(1) The current outbreak of COVID-19 reminds us how urgent this promise is and just how critical it is to continue to sustain and strengthen our nation's public health infrastructure. The unprecedented pace of the public health response to COVID-19 has only been possible because of prior investments in public health preparedness. To accelerate our pace and meet the challenges of current and future health threats, we must advance our world-class data and analytics capabilities; maintain and expand our state-of-the-art public health laboratory capacity; continue building a workforce of trusted, expert, public health professionals; sustain our capacity to rapidly respond to outbreaks at their source; and assure a strong global and domestic preparedness capacity. (Am J Public Health. Published online ahead of print February 13, 2020: e1-e2. doi:10.2105/AJPH.2020.305618).",2020,"Smith, Nathaniel; Fraser, Michael",Am J Public Health,3006223500,#878,
,CZI,PANDEMIC HUMAN CORONAVIRUS – CHARACTERIZATION AND COMPARISON OF SELECTED PROPERTIES OF HCOV-SARS AND HCOV-MERS,10.21307/PM-2018.57.1.022,,,,"It: Two Coronaviruses, HCoV-229E and HCoV-OC43, causing generally mild respiratory tract infections in humans, were described in the XX c. Pandemic Coronaviruses were first discovered as late as in the XXI c.: SARS-HCoV in 2002 – causing severe respiratory tract infections (SARS) in China; MERS-HCoV in 2012 – circulating mostly on the Arabian Peninsula. The SARS epidemic ended in 2004 resulting in morbidity of >8000 and >770 deaths, while the MERS epidemic is still ongoing (>2000 ill, >700 deaths) although its intensity decreased. Both viruses are zoonotic and require at least two “host jumps” for the transmission of the infection to humans: for HCoV-SARS – from bat to palm civet and then to human; for HCoV-MERS – from bats to camels and subsequently to humans. Primary mode of transmission is droplet in close contact (<1 m), but both viruses remain active in aerosol (up to 24 h), so infection can be also spread by air (ventilation). The ability for human-to-human transmission is higher for HCoV-SARS than for HCoV-MERS (8 generations vs. 4, respectively). Moreover, there are differences in genome structure and pathogenic mechanisms: different receptor, cell entry mechanism, different way of host response modulation (e.g. inhibition of IFNβ cascade), etc. Probably, these differences influence the overall manifestation of the disease in humans. Infection caused by HCoV-MERS might manifest itself as ARDS, a mild-mannered and asymptomatic disease. HCoV-SARS infections seem to be associated with severe disease only. In this paper, a comparison of the structure of these viruses, the mechanisms underlying their ability to cross the interspecies barrier and to multiply in the human body, including modulation of IFNβ cascade, as well as routes of infection transmission and symptoms caused, were presented.",2020,"Pancer, Katarzyna W.",Postępy Mikrobiologii,,#1790,
,CZI,"Early Transmissibility Assessment of a Novel Coronavirus in Wuhan, China",10.2139/ssrn.3524675,,,,"Between December 1, 2019 and January 26, 2020, nearly 3000 cases of respiratory illness caused by a novel coronavirus originating in Wuhan, China have been reported. In this short analysis, we combine publicly available cumulative case data from the ongoing outbreak with phenomenological modeling methods to conduct an early transmissibility assessment. Our model suggests that the basic reproduction number associated with the outbreak (at time of writing) may range from 2.0 to 3.1. Though these estimates are preliminary and subject to change, they are consistent with previous findings regarding the transmissibility of the related SARS-Coronavirus and indicate the possibility of epidemic potential.",,"Majumder, Maimuna and Mandl, Kenneth D.",SSRN,3001343166,#26,
,CZI,Coronavirus Disease COVID-19: A New Threat to Public Health,10.2174/1568026620999200305144319,,32133964,,,2020,"Kumar, S.; Poonam; Rathi, B.",Current topics in medicinal chemistry,2004242782,#4784,
,CZI,China Coronavirus Outbreak: All the Latest Updates,10.2174/1568026620999200305144537,,32133963,,,2020,"Scotti, Luciana; Scotti, Marcus T.",Current topics in medicinal chemistry,2999409984,#5206,
,CZI,Effective Chemicals against Novel Coronavirus (COVID-19) in China,10.2174/1568026620999200305145032,,32133962,,,2020,"Liu, Wei; Zhu, Hai-Liang; Duan, Yongtao",Current topics in medicinal chemistry,3005929298,#5452,
,CZI,COVID-19: Perspectives on the Potential Novel Global Threat,10.2174/1574887115999200228100745,,32116200,,,2020,"Gentile, Ivan; Abenavoli, Ludovico",Reviews on recent clinical trials,3006113744,#4112,
,CZI,Wuhan 2019 Novel Coronavirus Pneumonia: A Case Report of Serial Computed Tomographic Findings in a Female Patient (Preprint),10.2196/18129,,,,"UNSTRUCTURED Background: From December 2019, the 2019 Novel Coronavirus (2019-nCoV) Pneumonia broke out in Wuhan, China. In this study, we present the finding of serial computed tomography in a female patient with 2019-nCoV. Case presentation: We report a 40-year-old female who presented with the symptoms of fever, chest tightness, and fatigue. She was further diagnosed with 2019-nCoV confirmed by rRT-PCR. In terms of her chest CT findings, patchy consolidation shadows, and ground-glass opacities (GGOs) rapidly progressed in both lungs, peripherally. After treatment, the previous lesions were almost absorbed, leaving the fibrous lesions. Conclusions: If there is a history of fever or contact with the epidemic area, combined with the above CT findings, it is necessary to detect the nucleic acid of new coronavirus in time.",,"Wei, Jiangping; Xu, Huaxiang; Xiong, Jingliang; Shen, Qinglin; Fan, Bing; Ye, Chenglong; Dong, Wentao; Hu, Fangfang",,3005148615,#720,
,CZI,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: Chest CT Findings,10.2214/AJR.14.13021,,,,,2014,"Ajlan, Amr M.; Ahyad, Rayan A.; Jamjoom, Lamia Ghazi; Alharthy, Ahmed; Madani, Tariq A.",American Journal of Roentgenology,2112136274,#2448,
,CZI,Déjà Vu or Jamais Vu? How the Severe Acute Respiratory Syndrome Experience Influenced a Singapore Radiology Department's Response to the Coronavirus Disease (COVID-19) Epidemic,10.2214/AJR.20.22927,,32130047,,"OBJECTIVE. This article shares the ground operational perspective of how a tertiary hospital radiology department in Singapore is responding to the coronavirus disease (COVID-19) epidemic. This same department was also deeply impacted by the severe acute respiratory syndrome (SARS) outbreak in 2003. CONCLUSION. Though similar to SARS, the COVID-19 outbreak has several differences. We share how lessons from 2003 are applied and modified in our ongoing operational response to this evolving novel pathogen.",2020,"Cheng, Lionel Tim-Ee; Chan, Lai Peng; Tan, Ban Hock; Chen, Robert Chun; Tay, Kiang Hiong; Ling, Moi Lin; Tan, Bien Soo",AJR Am J Roentgenol,,#4602,
,CZI,Coronavirus Disease 2019 (COVID-19): Role of Chest CT in Diagnosis and Management,10.2214/AJR.20.22954,,32130038,,"OBJECTIVE. The objective of our study was to determine the misdiagnosis rate of radiologists for coronavirus disease 2019 (COVID-19) and evaluate the performance of chest CT in the diagnosis and management of COVID-19. The CT features of COVID-19 are reported and compared with the CT features of other viruses to familiarize radiologists with possible CT patterns. MATERIALS AND METHODS. This study included the first 51 patients with a diagnosis of COVID-19 infection confirmed by nucleic acid testing (23 women and 28 men; age range, 26-83 years) and two patients with adenovirus (one woman and one man; ages, 58 and 66 years). We reviewed the clinical information, CT images, and corresponding image reports of these 53 patients. The CT images included images from 99 chest CT examinations, including initial and follow-up CT studies. We compared the image reports of the initial CT study with the laboratory test results and identified CT patterns suggestive of viral infection. RESULTS. COVID-19 was misdiagnosed as a common infection at the initial CT study in two inpatients with underlying disease and COVID-19. Viral pneumonia was correctly diagnosed at the initial CT study in the remaining 49 patients with COVID-19 and two patients with adenovirus. These patients were isolated and obtained treatment. Ground-glass opacities (GGOs) and consolidation with or without vascular enlargement, interlobular septal thickening, and air bronchogram sign are common CT features of COVID-19. The The ""reversed halo"" sign and pulmonary nodules with a halo sign are uncommon CT features. The CT findings of COVID-19 overlap with the CT findings of adenovirus infection. There are differences as well as similarities in the CT features of COVID-19 compared with those of the severe acute respiratory syndrome. CONCLUSION. We found that chest CT had a low rate of missed diagnosis of COVID-19 (3.9%, 2/51) and may be useful as a standard method for the rapid diagnosis of COVID-19 to optimize the management of patients. However, CT is still limited for identifying specific viruses and distinguishing between viruses.",2020,"Li, Yan; Xia, Liming",AJR Am J Roentgenol,3006643024,#4517,
,CZI,Radiology Perspective of Coronavirus Disease 2019 (COVID-19): Lessons From Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome,10.2214/ajr.20.22969,,32108495,,"OBJECTIVE. Since the outbreak of the novel coronavirus pulmonary illness coronavirus disease 2019 (COVID-19) in China, more than 79,000 people have contracted the virus worldwide. The virus is rapidly spreading with human-to-human transmission despite imposed precautions. Because similar pulmonary syndromes have been reported from other strains of the coronavirus family, our aim is to review the lessons from imaging studies obtained during severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) outbreaks. CONCLUSION. The review of experiences with the MERS and SARS outbreaks will help us better understand the role of the radiologist in combating the outbreak of COVID-19. The known imaging manifestations of the novel coronavirus and the possible unknowns will also be discussed.",2020,"Hosseiny, M.; Kooraki, S.; Gholamrezanezhad, A.; Reddy, S.; Myers, L.",AJR. American journal of roentgenology,3006645647,#2833,
,CZI,"CT Features of Coronavirus Disease 2019 (COVID-19) Pneumonia in 62 Patients in Wuhan, China",10.2214/ajr.20.22975,,32134681,,"OBJECTIVE. The purpose of this study was to investigate 62 subjects in Wuhan, China, with laboratory-confirmed coronavirus disease (COVID-19) pneumonia and describe the CT features of this epidemic disease. MATERIALS AND METHODS. A retrospective study of 62 consecutive patients with laboratory-confirmed COVID-19 pneumonia was performed. CT images and clinical data were reviewed. Two thoracic radiologists evaluated the distribution and CT signs of the lesions and also scored the extent of involvement of the CT signs. The Mann-Whitney U test was used to compare lesion distribution and CT scores. The chi-square test was used to compare the CT signs of early-phase versus advanced-phase COVID-19 pneumonia. RESULTS. A total of 62 patients (39 men and 23 women; mean [+/- SD] age, 52.8 +/- 12.2 years; range, 30-77 years) with COVID-19 pneumonia were evaluated. Twenty-four of 30 patients who underwent routine blood tests (80.0%) had a decreased lymphocyte count. Of 27 patients who had their erythrocyte sedimentation rate and high-sensitivity C-reactive protein level assessed, 18 (66.7%) had an increased erythrocyte sedimentation rate, and all 27 (100.0%) had an elevated high-sensitivity C-reactive protein level. Multiple lesions were seen on the initial CT scan of 52 of 62 patients (83.9%). Forty-eight of 62 patients (77.4%) had predominantly peripheral distribution of lesions. The mean CT score for the upper zone (3.0 +/- 3.4) was significantly lower than that for the middle (4.5 +/- 3.8) and lower (4.5 +/- 3.7) zones (p = 0.022 and p = 0.020, respectively), and there was no significant difference in the mean CT score of the middle and lower zones (p = 1.00). The mean CT score for the anterior area (4.4 +/- 4.1) was significantly lower than that for the posterior area (7.7 +/- 6.3) (p = 0.003). CT findings for the patients were as follows: 25 patients (40.3%) had ground-glass opacities (GGO), 21 (33.9%), consolidation; 39 (62.9%), GGO plus a reticular pattern; 34 (54.8%), vacuolar sign; 28 (45.2%), microvascular dilation sign; 35 (56.5%), fibrotic streaks; 21 (33.9%), a subpleural line; and 33 (53.2%), a subpleural transparent line. With regard to bronchial changes seen on CT, 45 patients (72.6%) had air bronchogram, and 11 (17.7%) had bronchus distortion. In terms of pleural changes, CT showed that 30 patients (48.4%) had pleural thickening, 35 (56.5%) had pleural retraction sign, and six (9.7%) had pleural effusion. Compared with early-phase disease (</= 7 days after the onset of symptoms), advanced-phase disease (8-14 days after the onset of symptoms) was characterized by significantly increased frequencies of GGO plus a reticular pattern, vacuolar sign, fibrotic streaks, a subpleural line, a subpleural transparent line, air bronchogram, bronchus distortion, and pleural effusion; however, GGO significantly decreased in advanced-phase disease. CONCLUSION. CT examination of patients with COVID-19 pneumonia showed a mixed and diverse pattern with both lung parenchyma and the interstitium involved. Identification of GGO and a single lesion on the initial CT scan suggested early-phase disease. CT signs of aggravation and repair coexisted in advanced-phase disease. Lesions presented with a characteristic multifocal distribution in the middle and lower lung regions and in the posterior lung area. A decreased lymphocyte count and an increased high-sensitivity C-reactive protein level were the most common laboratory findings.",2020,"Zhou, S.; Wang, Y.; Zhu, T.; Xia, L.",AJR. American journal of roentgenology,3006354146,#5523,
,CZI,Relation Between Chest CT Findings and Clinical Conditions of Coronavirus Disease (COVID-19) Pneumonia: A Multicenter Study,10.2214/AJR.20.22976,,32125873,,"OBJECTIVE. The increasing number of cases of confirmed coronavirus disease (COVID-19) in China is striking. The purpose of this study was to investigate the relation between chest CT findings and the clinical conditions of COVID-19 pneumonia. MATERIALS AND METHODS. Data on 101 cases of COVID-19 pneumonia were retrospectively collected from four institutions in Hunan, China. Basic clinical characteristics and detailed imaging features were evaluated and compared between two groups on the basis of clinical status: nonemergency (mild or common disease) and emergency (severe or fatal disease). RESULTS. Patients 21-50 years old accounted for most (70.2%) of the cohort, and five (5.0%) patients had disease associated with a family outbreak. Most patients (78.2%) had fever as the onset symptom. Most patients with COVID-19 pneumonia had typical imaging features, such as ground-glass opacities (GGO) (87 [86.1%]) or mixed GGO and consolidation (65 [64.4%]), vascular enlargement in the lesion (72 [71.3%]), and traction bronchiectasis (53 [52.5%]). Lesions present on CT images were more likely to have a peripheral distribution (88 [87.1%]) and bilateral involvement (83 [82.2%]) and be lower lung predominant (55 [54.5%]) and multifocal (55 [54.5%]). Patients in the emergency group were older than those in the non-emergency group. Architectural distortion, traction bronchiectasis, and CT involvement score aided in evaluation of the severity and extent of the disease. CONCLUSION. Patients with confirmed COVID-19 pneumonia have typical imaging features that can be helpful in early screening of highly suspected cases and in evaluation of the severity and extent of disease. Most patients with COVID-19 pneumonia have GGO or mixed GGO and consolidation and vascular enlargement in the lesion. Lesions are more likely to have peripheral distribution and bilateral involvement and be lower lung predominant and multifocal. CT involvement score can help in evaluation of the severity and extent of the disease.",2020,"Zhao, Wei; Zhong, Zheng; Xie, Xingzhi; Yu, Qizhi; Liu, Jun",AJR Am J Roentgenol,2055651857,#3238,
,CZI,Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy,10.23812/20-Editorial-Kritas,,32013309,,"Coronavirus, which can cause respiratory syndrome, to date has affected over seventeen thousand individuals, especially in China. Coronavirus is interspecies and can also be transmitted from man to man, with an incubation ranging from 1 to 14 days. Human coronavirus infections can induce not only mild to severe respiratory diseases, but also inflammation, high fever, cough, acute respiratory tract infection and dysfunction of internal organs that may lead to death. Coronavirus infection (regardless of the various types of corona virus) is primarily attacked by immune cells including mast cells (MCs), which are located in the submucosa of the respiratory tract and in the nasal cavity and represent a barrier of protection against microorganisms. Viral activate MCs release early inflammatory chemical compounds including histamine and protease; while late activation provokes the generation of pro-inflammatory IL-1 family members including IL-1, IL-6 and IL-33. Here, we propose for the first time that inflammation by coronavirus may be inhibited by anti-inflammatory cytokines belonging to the IL-1 family members.",2019,"Kritas, S. K.; Ronconi, G.; Caraffa, Al; Gallenga, C. E.; Ross, R.; Conti, P.",J Biol Regul Homeost Agents,2119445255,#3716,
,CZI,Identification of Coronavirus Isolated from a Patient in Korea with COVID-19,10.24171/j.phrp.2020.11.1.02,,,,"Objectives Following reports of patients with unexplained pneumonia at the end of December 2019 in Wuhan, China, the causative agent was identified as coronavirus (SARS-CoV-2), and the 2019 novel coronavirus disease was named COVID-19 by the World Health Organization. Putative patients with COVID-19 have been identified in South Korea, and attempts have been made to isolate the pathogen from these patients. Methods Upper and lower respiratory tract secretion samples from putative patients with COVID-19 were inoculated onto cells to isolate the virus. Full genome sequencing and electron microscopy were used to identify the virus. Results The virus replicated in Vero cells and cytopathic effects were observed. Full genome sequencing showed that the virus genome exhibited sequence homology of more than 99.9% with SARS-CoV-2 which was isolated from patients from other countries, for instance China. Sequence homology of SARS-CoV-2 with SARS-CoV, and MERS-CoV was 77.5% and 50%, respectively. Coronavirus-specific morphology was observed by electron microscopy in virus-infected Vero cells. Conclusion SARS-CoV-2 was isolated from putative patients with unexplained pneumonia and intermittent coughing and fever. The isolated virus was named BetaCoV/Korea/KCDC03/2020.",2020,"Han, Jeong-Min Kim; Yoon-Seok, Chung; Hye Jun, Jo; Nam-Joo, Lee; Mi Seon, Kim; Sang Hee, Woo; Sehee, Park; Jee Woong, Kim; Heui Man, Kim; Myung, Guk",Osong Public Health and Research Perspectives,3005657121,#2631,
,CZI,Early Epidemiological and Clinical Characteristics of 28 Cases of Coronavirus Disease in South Korea,10.24171/j.phrp.2020.11.1.03,,,,"The first confirmed case of coronavirus disease 2019 (COVID-19) in South Korea was reported in January 2020, with 28 confirmed cases reported as of February 14th, 2020. The epidemiological and clinical characteristics of all 28 cases were analyzed in response to this disease. Methods The epidemiological characteristics and early clinical features of the 28 patients from Korea with confirmed COVID-19 were analyzed using COVID-19 reporting and surveillance data and the epidemiological investigation reports prepared by the rapid response team. Results There were 16 patients that entered Korea from foreign countries: Wuhan, China (11 patients), Zhuhai, China, (1 patient), Singapore (2 patients), Japan (1 patient), and Thailand (1 patient). The early symptoms were fever, sore throat, cough or sputum production, chills, and muscle ache. Three patients were asymptomatic, however, 18 developed pneumonia. Of the 28 cases, 16 were index cases imported from abroad, with 10 cases of secondary infection originating in Korea, and the route of transmission still under investigation for 2 patients. The 10 patients with secondary infection were infected from contact with family members or acquaintances of primary patients, and the suspected sites of transmission were mostly at home. Conclusion COVID-19 in Korea was spread by 16 infected individuals traveling from other countries, leading to second-generation cases. The initial symptoms were mostly minor, but the disease was infectious at this stage, resulting from close contact, particularly at home. Establishing an early detection strategy for COVID-19 is crucial for managing the transmission of the disease.",2020,,Osong Public Health and Research Perspectives,2981256933,#2688,
,CZI,Contact Transmission of COVID-19 in South Korea: Novel Investigation Techniques for Tracing Contacts,10.24171/j.phrp.2020.11.1.09,,,,"In the epidemiological investigation of an infectious disease, investigating, classifying, tracking, and managing contacts by identifying the patient’s route are important for preventing further transmission of the disease. However, omissions and errors in previous activities can occur when the investigation is performed through only a proxy interview with the patient. To overcome these limitations, methods that can objectively verify the patient’s claims (medical facility records, Global Positioning System, card transactions, and closed-circuit television) were used for the recent ongoing coronavirus disease 2019 contact investigations in South Korea.",2020,,Osong Public Health and Research Perspectives,119142419,#2687,
,CZI,Data sharing for novel coronavirus (COVID-19),10.2471/blt.20.251561,,32132744,,,2020,"Moorthy, Vasee; Henao Restrepo, Ana Maria; Preziosi, Marie-Pierre; Swaminathan, Soumya",Bulletin of the World Health Organization,3006223500,#4910,
,CZI,Expert Recommendations for Tracheal Intubation in Critically ill Patients with Noval Coronavirus Disease 2019,10.24920/003724,,32102726,,"Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), is a highly contagious disease. It firstly appeared in Wuhan, Hubei province of China in December 2019. During the next two months, it moved rapidly throughout China and spread to multiple countries through infected persons travelling by air. Most of the infected patients have mild symptoms including fever, fatigue and cough. But in severe cases, patients can progress rapidly and develop to the acute respiratory distress syndrome, septic shock, metabolic acidosis and coagulopathy. The new coronavirus was reported to spread via droplets, contact and natural aerosols from human-to-human. Therefore, high-risk aerosol-producing procedures such as endotracheal intubation may put the anesthesiologists at high risk of nosocomial infections. In fact, SARS-CoV-2 infection of anesthesiologists after endotracheal intubation for confirmed COVID-19 patients have been reported in hospitals in Wuhan. The expert panel of airway management in Chinese Society of Anaesthesiology has deliberated and drafted this recommendation, by which we hope to guide the performance of endotracheal intubation by frontline anesthesiologists and critical care physicians. During the airway management, enhanced droplet/airborne PPE should be applied to the health care providers. A good airway assessment before airway intervention is of vital importance. For patients with normal airway, awake intubation should be avoided and modified rapid sequence induction is strongly recommended. Sufficient muscle relaxant should be assured before intubation. For patients with difficult airway, good preparation of airway devices and detailed intubation plans should be made.",2020,"Zuo, M. Z.; Huang, Y. G.; Ma, W. H.; Xue, Z. G.; Zhang, J. Q.; Gong, Y. H.; Che, L.",Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih,2017345465,#3041,
,CZI,COVID-19 (Novel Coronavirus 2019) - recent trends,10.26355/eurrev_202002_20378,,32141569,,"The World Health Organization (WHO) has issued a warning that, although the 2019 novel coronavirus (COVID-19) from Wuhan City (China), is not pandemic, it should be contained to prevent the global spread. The COVID-19 virus was known earlier as 2019-nCoV. As of 12 February 2020, WHO reported 45,171 cases and 1115 deaths related to COVID-19. COVID-19 is similar to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) virus in its pathogenicity, clinical spectrum, and epidemiology. Comparison of the genome sequences of COVID-19, SARS-CoV, and Middle East Respiratory Syndrome coronavirus (MERS-CoV) showed that COVID-19 has a better sequence identity with SARS-CoV compared to MERS CoV. However, the amino acid sequence of COVID-19 differs from other coronaviruses specifically in the regions of 1ab polyprotein and surface glycoprotein or S-protein. Although several animals have been speculated to be a reservoir for COVID-19, no animal reservoir has been already confirmed. COVID-19 causes COVID-19 disease that has similar symptoms as SARS-CoV. Studies suggest that the human receptor for COVID-19 may be angiotensin-converting enzyme 2 (ACE2) receptor similar to that of SARS-CoV. The nucleocapsid (N) protein of COVID-19 has nearly 90% amino acid sequence identity with SARS-CoV. The N protein antibodies of SARS-CoV may cross react with COVID-19 but may not provide cross-immunity. In a similar fashion to SARS-CoV, the N protein of COVID-19 may play an important role in suppressing the RNA interference (RNAi) to overcome the host defense. This mini-review aims at investigating the most recent trend of COVID-19.",2020,"Kannan, S.; Shaik Syed Ali, P.; Sheeza, A.; Hemalatha, K.",European review for medical and pharmacological sciences,3005943294,#4760,
,CZI,"Novel coronavirus 2019-nCoV: prevalence, biological and clinical characteristics comparison with SARS-CoV and MERS-CoV",10.26355/eurrev_202002_20379,,32141570,,"OBJECTIVE: Human infections with zoonotic coronavirus contain emerging and reemerging pathogenic characteristics which have raised great public health concern. This study aimed at investigating the global prevalence, biological and clinical characteristics of novel coronavirus, Wuhan China (2019-nCoV), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection outbreaks. MATERIALS AND METHODS: The data on the global outbreak of ""2019-nCoV, SARS-CoV, and MERS-CoV"" were obtained from World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), concerned ministries and research institutes. We also recorded the information from research documents published in global scientific journals indexed in ISI Web of Science and research centers on the prevalence, biological and clinical characteristics of 2019-nCoV, SARS-CoV, and MERS-CoV. RESULTS: Worldwide, SARS-CoV involved 32 countries, with 8422 confirmed cases and 916 (10.87%) casualties from November 2002 to August 2003. MERS-CoV spread over 27 states, causing 2496 cases and 868 (34.77%) fatalities during the period April 2012 to December 2019. However, the novel coronavirus 2019-nCoV spread swiftly the global borders of 27 countries. It infected 34799 people and resulted in 724 (2.08%) casualties during the period December 29, 2019 to February 7, 2020. The fatality rate of coronavirus MERS-CoV was (34.77%) higher than SARS-CoV (10.87%) and 2019-nCoV (2.08%); however, the 2019-nCoV transmitted rapidly in comparison to SARS-CoV and MERS-CoV. CONCLUSIONS: The novel coronavirus 2019-nCoV has diverse epidemiological and biological characteristics, making it more contagious than SARS-CoV and MERS-CoV. It has affected more people in a short time period compared to SARS-CoV and MERS-CoV, although the fatality rate of MERS-CoV was higher than SARS-CoV and 2019-nCoV. The major clinical manifestations in coronavirus infections 2019-nCoV, MERS-CoV, and SARS CoV are fever, chills, cough, shortness of breath, generalized myalgia, malaise, drowsy, diarrhea, confusion, dyspnea, and pneumonia. Global health authorities should take immediate measures to prevent the outbreaks of such emerging and reemerging pathogens across the globe to minimize the disease burden locally and globally.",2020,"Meo, S. A.; Alhowikan, A. M.; Al-Khlaiwi, T.; Meo, I. M.; Halepoto, D. M.; Iqbal, M.; Usmani, A. M.; Hajjar, W.; Ahmed, N.",European review for medical and pharmacological sciences,3005122137,#4906,
,CZI,Burden of acute respiratory disease of epidemic and pandemic potential in the WHO Eastern Mediterranean Region: A literature review,10.26719/2016.22.7.509,,,,"There are gaps in the knowledge about the burden of severe respiratory disease in the Eastern Mediterranean Region (EMR). This literature review was therefore conducted to describe the burden of epidemic-and pandemic-prone acute respiratory infections (ARI) in the Region which may help in the development of evidence-based disease prevention and control policies. Relevant published and unpublished reports were identified from searches of various databases; 83 documents fulfilled the search criteria. The infections identified included: ARI, avian influenza A(H5N1), influenza A(H1N1)pdm09 and Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Pneumonia and ARIs were leading causes of disease and death in the Region. Influenza A(H1N1) was an important cause of morbidity during the 2009 pandemic. This review provides a descriptive summary of the burden of acute respiratory diseases in the Region, but there still remains a lack of necessary data. On observe des lacunes en matière de connaissances concernant la charge des maladies respiratoires sévères dans la Région de la Méditerranée orientale. La présente analyse documentaire détaille la charge des infections respiratoires aiguës (IRA) à potentiel épidémique et pandémique dans la Région, ce qui peut aider à l'élaboration de politiques et programmes de prévention et de lutte contre les maladies reposant sur des données factuelles. Des articles pertinents publiés et non publiés ont été identifiés grâce à des recherches dans différentes bases de données ; 83 documents satisfaisaient à nos critères de recherche. Les infections identifiées comprenaient les infections respiratoires aiguës (IRA), la grippe aviaire A(H5N1), la grippe A(H1N1)pdm09 et l'infection par le coronavirus du syndrome respiratoire du Moyen-Orient (MERS-CoV). La pneumonie et les IRA constituaient les principales causes de morbidité et de mortalité dans la Région. La grippe A(H1N1) était une cause importante de morbidité durant la pandémie de 2009. Cette analyse fournit un résumé descriptif de la charge des maladies respiratoires aiguës dans la Région mais il existe toujours une lacune concernant les donneés nécessaires à cet égard.",2016,"Abubakar, A.; Malik, M.; Pebody, R. G.; Elkholy, A. A.; Khan, W.; Bellos, A.; Mala, P.",Eastern Mediterranean Health Journal,2529381635,#2453,
,CZI,Coronavirus disease 2019 outbreak: Preparedness and readiness of countries in the eastern mediterranean region,10.26719/2020.26.2.136,,,,,2020,"Al-Mandhari, A.; Samhouri, D.; Abubakar, A.; Brennan, R.",Eastern Mediterranean Health Journal,3006609801,#5026,
,CZI,"First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020",10.2807/1560-7917.es.2020.25.6.2000094,,,,"A cluster of pneumonia of unknown origin was identified in Wuhan, China, in December 2019 [1]. On 12 January 2020, Chinese authorities shared the sequence of a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from some clustered cases [2]. Since then, the disease caused by SARS-CoV-2 has been named coronavirus disease 2019 (COVID-19). As at 21 February 2020, the virus had spread rapidly mostly within China but also to 28 other countries, including in the World Health Organization (WHO) European Region [3-5]. Here we describe the epidemiology of the first cases of COVID-19 in this region, excluding cases reported in the United Kingdom (UK), as at 21 February 2020. The study includes a comparison between cases detected among travellers from China and cases whose infection was acquired due to subsequent local transmission.%R doi:https://doi.org/10.2807/1560-7917.ES.2020.25.9.2000178",2020,"Spiteri, Gianfranco; Fielding, James; Diercke, Michaela; Campese, Christine; Enouf, Vincent; Gaymard, Alexandre; Bella, Antonino; Sognamiglio, Paola; Sierra Moros, Maria José; Riutort, Antonio Nicolau; Demina, Yulia V.; Mahieu, Romain; Broas, Markku; Bengnér, Malin; Buda, Silke; Schilling, Julia; Filleul, Laurent; Lepoutre, Agnès; Saura, Christine; Mailles, Alexandra; Levy-Bruhl, Daniel; Coignard, Bruno; Bernard-Stoecklin, Sibylle; Behillil, Sylvie; van der Werf, Sylvie; Valette, Martine; Lina, Bruno; Riccardo, Flavia; Nicastri, Emanuele; Casas, Inmaculada; Larrauri, Amparo; Salom Castell, Magdalena; Pozo, Francisco; Maksyutov, Rinat A.; Martin, Charlotte; Van Ranst, Marc; Bossuyt, Nathalie; Siira, Lotta; Sane, Jussi; Tegmark-Wisell, Karin; Palmérus, Maria; Broberg, Eeva K.; Beauté, Julien; Jorgensen, Pernille; Bundle, Nick; Pereyaslov, Dmitriy; Adlhoch, Cornelia; Pukkila, Jukka; Pebody, Richard; Olsen, Sonja; Ciancio, Bruno Christian",Eurosurveillance,3006007867,#4442,
,CZI,Coronavirus latest: WHO officially names disease COVID-19,10.2807/1560-7917.es.2020.25.6.2000094,,,,"The World Health Organization has officially named the disease caused by the coronavirus COVID-19. This will replace various monikers and hashtags given to the emerging illness over the past few weeks. Most recently, on 8 February, China’s National Health Commission decided to temporarily call the disease novel coronavirus pneumonia, or NCP. But because viruses continue to spread from animals to people, this coronavirus won’t be novel for long.",2020,Science,Science,3006007867,#687,
,CZI,Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak,10.2807/1560-7917.es.2020.25.6.2000110,,,,"Infections with 2019-nCoV can spread from person to person, and in the earliest phase of the outbreak the basic reproductive number was estimated to be around 2.2, assuming a mean serial interval of 7.5 days [2]. The serial interval was not precisely estimated, and a potentially shorter mean serial interval would have corresponded to a slightly lower basic reproductive number. Control measures and changes in population behaviour later in January should have reduced the effective reproductive number. However, it is too early to estimate whether the effective reproductive number has been reduced to below the critical threshold of 1 because cases currently being detected and reported would have mostly been infected in mid- to late-January. Average delays between infection and illness onset have been estimated at around 5–6 days, with an upper limit of around 11-14 days [2,5], and delays from illness onset to laboratory confirmation added a further 10 days on average [2].",,"Cowling, Benjamin J; Leung, Gabriel M",Eurosurveillance,3006044875,#675,
,CZI,Evaluation of a quantitative RT-PCR assay for the detection of the emerging coronavirus SARS-CoV-2 using a high throughput system,10.2807/1560-7917.ES.2020.25.9.2000152,,,,"The ability to quickly confirm or clear suspected cases is crucial during global outbreak scenarios, especially when clinical manifestations are difficult to distinguish from other respiratory infections such as influenza, molecular diagnostics is key for detection of the emerging virus. A variety of suitable assays were made available early on during the course of the outbreak, notably by Corman et al. and others [4,5]. However, their implementation in the diagnostics laboratory usually relies on manual PCR setups requiring a high degree of human interaction for execution and interpretation, thus limiting their capacity to be scaled up for handling large numbers of samples. In this study we report the analytical evaluation of a laboratory-developed test for the detection of SARS-CoV-2 using the open channel (utility channel) of the cobas 6800 system.%U https://eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.9.2000152",2020,"Pfefferle, Susanne; Reucher, Svenja; Nörz, Dominic; Lütgehetmann, Marc",Eurosurveillance,2033377462,#4473,
,CZI,"Rapid establishment of laboratory diagnostics for the novel coronavirus SARS-CoV-2 in Bavaria, Germany, February 2020",10.2807/1560-7917.ES.2020.25.9.2000173,,,,"In connection with the ongoing outbreak of a novel coronavirus in the province Hubei and surrounding areas in China, it was expected that Europe would also be confronted with the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as infections in travellers in several Asian countries outside of China were confirmed shortly after the announcement of the outbreak in Wuhan [1-4]. Therefore, it was necessary to rapidly implement adequately quick and sensitive diagnostic assays for outbreak management of SARS-CoV-2 in public health laboratories. As soon as the World Health Organization (WHO) published the first protocols for real-time RT-PCR assays, the Bavarian Food and Health Authority started to implement them. We ordered control material and oligonucleotides (see details below) in week 4 and ran our first SARS-CoV-2 assays on 27 January (week 5). On the same day, the first German case of coronavirus disease 2019 (COVID-19) was diagnosed in Bavaria [1]. In the following days, health authorities implemented comprehensive measures to prevent further transmission of SARS-CoV-2, including testing of contact persons. We initially used the protocol based on the E gene and RdRp gene developed by the German Consiliary Laboratory for Coronaviruses hosted at the Charité in Berlin [5]. Real-time RT-PCR was initially performed with the QuantiTect Virus +Rox Vial kit (QIAGEN, Hilden, Germany) on the Bio-Rad CFX96 Touch Real-Time PCR Detection System (Bio-Rad, Feldkirchen, Germany). The kit was chosen for its frequent and successful use in our laboratory with other assays and its immediate availability. Primers and probes were used as described [5] and provided by TIB Molbiol (Berlin, Germany). Control material was ordered from the European Virus Archive (EVAg) and consisted of synthetic Wuhan coronavirus 2019 E gene control (reference number 026N-03866) and SARS-CoV Frankfurt 1 RNA (reference number 004N-02005) [6]. In addition, the control of LightMix Modular Wuhan CoV RdRP-gene (TibMolbiol, Berlin, Germany) was used for the SARS-CoV-2 specific assay. Respiratory samples (nasopharyngeal swabs or sputum) were obtained from patients and contact persons. Sputum samples were diluted in 2 mL phosphate buffered saline (PBS). RNA was extracted using the QIAamp Bio Robot kit (QIAGEN) on a Hamilton Microlab Star (Hamilton, Bonaduz, Switzerland). As at 1 March, 87,024 cases and 2,979 associated deaths have been reported worldwide [1]. The vast majority of the deaths (96%) have been reported in China [1]. Despite the high number of cases reported globally, estimates of the severity pyramid of disease and case fatality rate remain very uncertain; one large study conducted in China estimated that the majority (81%) of the cases were mild (i.e. non-pneumonia or mild pneumonia), 14% were severe (e.g. with dyspnoea) and 5% were in a critical condition (i.e. respiratory failure, septic shock and/or multiple organ dysfunction/failure) [2]. The case fatality ratio was 2.3% [2]. Despite extraordinary containment measures implemented in China, including the enforced lockdown of several cities and closures of schools, the virus has spread throughout the country and internationally [2]. It is too early to predict with any certainty the epidemiological developments over the coming weeks, but the possibility of widespread community transmission becoming established throughout the EU/EEA is becoming increasingly likely.",2020,"Konrad, Regina; Eberle, Ute; Dangel, Alexandra; Treis, Bianca; Berger, Anja; Bengs, Katja; Fingerle, Volker; Liebl, Bernhard; Ackermann, Nikolaus; Sing, Andreas",Eurosurveillance,3005538648,#4532,
,CZI,Updated rapid risk assessment from ECDC on the outbreak of COVID-19: increased transmission globally,10.2807/1560-7917.ES.2020.25.9.2003051,,,,"The European Centre for Disease Prevention and Control (ECDC) provides regularly updated information on coronavirus disease-2019 (COVID-19) relevant to Europe on a dedicated webpage. Besides general information including Q&As, daily case counts, and maps with disease distribution, examples of latest updates comprise: Resource estimation for contact tracing, quarantine and monitoring activities for COVID-19 cases in the EU/EEA, Guidance for wearing and removing personal protective equipment in healthcare settings for the care of patients with suspected or confirmed COVID-19 and Checklist for hospitals preparing for the reception and care of coronavirus 2019 (COVID-19) patients. ECDC also publishes regular risk assessments and the Box below contains the summary from the fifth update published on 2 March 2020.%U https://eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.9.2003051",2020,"team, Eurosurveillance editorial",Eurosurveillance,3006211350,#4434,
,CZI,Perinatal novel coronavirus infection: a case report,10.2807/ese.18.08.20406-en,,,,"We hereby reported the diagnosis, treatment process and perinatal outcome of a patient with novel coronavirus infection in perinatal period. The pregnant woman delivered a boy by cesarean section at 37 +2 gestational weeks due to severe liver dysfunction. She subsequently had a high fever 2 days later, and novel coronavirus infection was confirmed by nucleic acid test in a throat swab. After a 12-day isolation and support treatment, her two consecutive throat swab results for novel coronavirus turned negative and she was discharged. The novel coronavirus was tested in the patient's blood, urine, breast milk as well as the neonatal throat swab, and the results were all negative. The neonate had an elevated myocardial enzyme, but was otherwise well and was discharged after 14-day isolation with normal myocardial enzyme.",2020,"ZHUANG, Siying; GUO, Juanjuan; CAO, Yuming; CHEN, Huijun; XU, Dan; LI, Jiafu; ZHANG, Yuanzhen",Chinese Journal of Perinatal Medicine,1736130314,#2038,
,CZI,Air Medical Evacuation of Nepalese Citizen During Epidemic of COVID-19 from Wuhan to Nepal,10.31729/jnma.4857,,,,"In December 2019, the world was disrupted by the news of a new strain of virus known as Novel Corona virus, taking lives of many in China. Wuhan, the capital of Central China’s Hubei province is said to be the place where the outbreak started. The city went on a lockdown as the disease spread rapidly. After the lockdown, most countries like India and Bangladesh airlifted their citizens who were studying in Wuhan. Similarly, Nepal also has many youth studying medicine in Wuhan. Pleas for help from the students reached the government. This was a first encounter of such experience for Nepal government. With the help of Health Emergency Organizing committee, Epidemiology and Disease Control Division, Nepal Army Hospital, Nepal Police Hospital, Waste Management team, Nepal Ambulance service, Tribhuwan Airport and Royal Airlines the government of Nepal planned, organized and successfully brought back all the 175 students on 15 the February, 2019 from Wuhan, China. The aim of the present article is to share the experience, the challenges faced and recommendations for future similar cases.",2020,"Thapa, Bibek Rajbhandari; Naveen, Phuyal; Bikal, Shrestha; Moon",Journal of Nepal Medical Association,2074966216,#4431,
,CZI,The laboratory risk assessment and control testing 2019 novel coronavirus in biosafety class II laboratories,10.3201/eid2605.200146,,,,"The outbreak of 2019 Novel Coronavirus (2019-nCoV) has spread from Wuhan to the whole country. After the Spring Festival, workers will return to workplace and students will return to school. There is an increasing risk of 2019-nCoV cases being imported into provinces and cities. In order to promote the prevention and control of 2019-nCoV infection, reduce the risk of transmission in medical institutions, and ensure medical quality and medical safety, it is necessary to carry out the detection test of 2019-nCoV in biosafety class II laboratory. In order to achieve the goal of zero infection of the laboratory personnel, different preventive measures should be taken to assess the risk of the experimental activities.",2020,"HUA, Wenhao; SHENG, Linjun; SONG, Lihong; WANG, Qingtao",Chinese Journal of Laboratory Medicine,3006320625,#2258,
,CZI,"Lack of Vertical Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, China",10.3201/eid2606.200287,,32134381,,A woman with 2019 novel coronavirus disease in her 35th week of pregnancy delivered an infant by cesarean section in a negative-pressure operating room. The infant was negative for severe acute respiratory coronavirus 2. This case suggests that mother-to-child transmission is unlikely for this virus.,2020,"Li, Y.; Zhao, R.; Zheng, S.; Chen, X.; Wang, J.; Sheng, X.; Zhou, J.; Cai, H.; Fang, Q.; Yu, F.; Fan, J.; Xu, K.; Chen, Y.; Sheng, J.",Emerging infectious diseases,2116732940,#4834,
,CZI,"2019-nCoV acute respiratory disease, Australia: Epidemiology Report 1 (Reporting week 26 January - 1 February 2020)",10.33321/cdi.2020.44.13,,32027812,,"This is the first epidemiological report of novel coronavirus (2019-nCoV) acute respiratory disease infections reported in Australia at 19:00 Australian Eastern Daylight Time [AEDT] 1 February 2020. It includes data on Australian cases notified during the week 26 January to 1 February 2020 and in the previous week (19 to 25 January 2020), the international situation and current information on the severity, transmission and spread of the 2019-nCoV infection.",2020,"nCo, V. National Incident Room Surveillance Team",Commun Dis Intell (2018),3004914321,#475,
,CZI,"COVID-19, Australia: Epidemiology Report 2 (Reporting week ending 19:00 AEDT 8 February 2020)",10.33321/cdi.2020.44.14,,32050080,,"This is the second epidemiological report for coronavirus disease (COVID-19), previously known as novel coronavirus (2019-nCoV), reported in Australia as at 19:00 Australian Eastern Daylight Time [AEDT] 8 February 2020. It includes data on Australian cases notified during the week ending 19:00 AEDT 8 February 2020, the international situation and current information on the severity, transmission and spread of the COVID-19 infection.",2020,"Team, Covid- National Incident Room Surveillance",Commun Dis Intell (2018),3006338236,#727,
,CZI,"COVID-19, Australia: Epidemiology Report 3 (Reporting week ending 19:00 AEDT 15 February 2020)",10.33321/cdi.2020.44.15,,32074480,,"This is the third epidemiological report for coronavirus disease 2019 (COVID-19), previously known as novel coronavirus (2019-nCoV), from the virus now known as SARS-CoV-2, reported in Australia as at 19:00 Australian Eastern Daylight Time [AEDT] 15 February 2020. It includes data on the COVID-19 Australian cases, the international situation and current information on the severity, transmission and spread.",2020,"Team, Covid- National Incident Room Surveillance",Commun Dis Intell (2018),3006338236,#1485,
,CZI,"COVID-19, Australia: Epidemiology Report 4 (Reporting week ending 19:00 AEDT 22 February 2020)",10.33321/cdi.2020.44.17,,32098616,,"This is the fourth epidemiological report for coronavirus disease 2019 (COVID-19), reported in Australia as at 19:00 Australian Eastern Daylight Time [AEDT] 22 February 2020. It includes data on COVID-19 cases diagnosed in Australia, the international situation and a review of current evidence.",2020,"Team, Covid- National Incident Room Surveillance",Commun Dis Intell (2018),3006338236,#2377,
,CZI,"COVID-19, Australia: Epidemiology Report 5 (Reporting week ending 19:00 AEDT 29 February 2020)",10.33321/cdi.2020.44.20,,32126197,,"This is the fifth epidemiological report for coronavirus disease 2019 (COVID-19), reported in Australia as at 19:00 Australian Eastern Daylight Time [AEDT] 29 February 2020. It includes data on COVID-19 cases diagnosed in Australia, the international situation and a review of current evidence.",2020,"Team, Covid- National Incident Room Surveillance",Commun Dis Intell (2018),3006338236,#3292,
,CZI,The Fight against the 2019-nCoV Outbreak: an Arduous March Has Just Begun,10.3346/jkms.2020.35.e56,,,,&lt;![CDATA[No abstract available.]]&gt;,2020,"YOO, Jin Hong",Journal of Korean Medical Science,3003274018,#1017,
,CZI,"The First Case of 2019 Novel Coronavirus Pneumonia Imported into Korea from Wuhan, China: Implication for Infection Prevention and Control Measures",10.3346/jkms.2020.35.e61,,,,"In December 2019, a viral pneumonia outbreak caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV), began in Wuhan, China. We report the epidemiological and clinical features of the first patient with 2019-nCoV pneumonia imported into Korea from Wuhan. This report suggests that in the early phase of 2019-nCoV pneumonia, chest radiography would miss patients with pneumonia and highlights taking travel history is of paramount importance for early detection and isolation of 2019-nCoV cases.",2020,"Kim, Jin Yong",Journal of Korean Medical Science,3004790666,#3705,
,CZI,Case of the Index Patient Who Caused Tertiary Transmission of COVID-19 Infection in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Infected Pneumonia Monitored by Quantitative RT-PCR,10.3346/jkms.2020.35.e79,,,,"Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, ß-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.",2020,"Lim, Jaegyun; Jeon, Seunghyun; Shin, Hyun Young; Kim, Moon Jung; Seong, Yu Min; Lee, Wang Jun; Choe, Kang Won; Kang, Yu Min; Lee, Baeckseung; Park, Sang Joon",J Korean Med Sci,3005657121,#861,
,CZI,THREE NOTICEABLE ISSUES ON NOVEL CORONAVIRUS: A QUICK LOOK FROM VIETNAM’S CIRCUMSTANCES,10.33546/bnj.1058,,,,"Novel Coronavirus officially COVID-19 has been detected since December 2019 and it has become a global health issue concern today. According to the statistics from the Vietnam’s Ministry of Health, until 13February 2020, Vietnam has fifteen positive cases with COVID-19, which one of those is a 3-month-old baby (Ministry of Health, 2020). It is estimated that the COVID-19 outbreak will be reached the top in the next ten days due to the excessive worrying and wrong behaviors towards the virus (Thu, 2020). In this letter, the author presents three noticeable issues based on the current situation in Vietnam and efforts that nurses should do",2020,"Tuyen, Le Thi Thanh",6,,#881,
,CZI,"Understanding Unreported Cases in the COVID-19 Epidemic Outbreak in Wuhan, China, and the Importance of Major Public Health Interventions",10.3390/biology9030050,,,,"We develop a mathematical model to provide epidemic predictions for the COVID-19 epidemic in Wuhan, China. We use reported case data up to 31 January 2020 from the Chinese Center for Disease Control and Prevention and the Wuhan Municipal Health Commission to parameterize the model. From the parameterized model, we identify the number of unreported cases. We then use the model to project the epidemic forward with varying levels of public health interventions. The model predictions emphasize the importance of major public health interventions in controlling COVID-19 epidemics.",2020,"Liu, Zhihua; Magal, Pierre; Seydi, Ousmane; Webb, Glenn",Biology,3005301080,#5460,
,CZI,Rigidity of the Outer Shell Predicted by a Protein Intrinsic Disorder Model Sheds Light on the COVID-19 (Wuhan-2019-nCoV) Infectivity,10.3390/biom10020331,,,,"The world is currently witnessing an outbreak of a new coronavirus spreading quickly across China and affecting at least 24 other countries. With almost 65,000 infected, a worldwide death toll of at least 1370 (as of 14 February 2020), and with the potential to affect up to two-thirds of the world population, COVID-19 is considered by the World Health Organization (WHO) to be a global health emergency. The speed of spread and infectivity of COVID-19 (also known as Wuhan-2019-nCoV) are dramatically exceeding those of the Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). In fact, since September 2012, the WHO has been notified of 2494 laboratory-confirmed cases of infection with MERS-CoV, whereas the 2002&ndash;2003 epidemic of SARS affected 26 countries and resulted in more than 8000 cases. Therefore, although SARS, MERS, and COVID-19 are all the result of coronaviral infections, the causes of the coronaviruses differ dramatically in their transmissibility. It is likely that these differences in infectivity of coronaviruses can be attributed to the differences in the rigidity of their shells which can be evaluated using computational tools for predicting intrinsic disorder predisposition of the corresponding viral proteins.",2020,"Goh, Gerard Kian-Meng; Dunker, A. Keith; Foster, James A.; Uversky, Vladimir N.",Biomolecules,2794226826,#1308,
,CZI,Antiviral Action of Tryptanthrin Isolated from Strobilanthes cusia Leaf against Human Coronavirus NL63 Outbreak of Novel Coronavirus (SARS-Cov-2): First Evidences From International Scientific Literature and Pending Questions,10.3390/biom10030366 10.3390/healthcare8010051,,,,"Strobilanthes cusia (Nees) Kuntze is a Chinese herbal medicine used in the treatment of respiratory virus infections. The methanol extract of S. cusia leaf contains chemical components such as &beta;-sitosterol, indirubin, tryptanthrin, betulin, indigodole A, and indigodole B that have diverse biological activities. However, the antiviral action of S. cusia leaf and its components against human coronavirus remains to be elucidated. Human coronavirus NL63 infection is frequent among immunocompromised individuals, young children, and in the elderly. This study investigated the anti-Human coronavirus NL63 (HCoV-NL63) activity of the methanol extract of S. cusia leaf and its major components. The methanol extract of S. cusia leaf effectively inhibited the cytopathic effect (CPE) and virus yield (IC50 = 0.64 &mu;g/mL) in HCoV-NL63-infected cells. Moreover, this extract potently inhibited the HCoV-NL63 infection in a concentration-dependent manner. Among the six components identified in the methanol extract of S. cusia leaf, tryptanthrin and indigodole B (5aR-ethyltryptanthrin) exhibited potent antiviral activity in reducing the CPE and progeny virus production. The IC50 values against virus yield were 1.52 &mu;M and 2.60 &mu;M for tryptanthrin and indigodole B, respectively. Different modes of time-of-addition/removal assay indicated that tryptanthrin prevented the early and late stages of HCoV-NL63 replication, particularly by blocking viral RNA genome synthesis and papain-like protease 2 activity. Notably, tryptanthrin (IC50 = 0.06 &mu;M) and indigodole B (IC50 = 2.09 &mu;M) exhibited strong virucidal activity as well. This study identified tryptanthrin as the key active component of S. cusia leaf methanol extract that acted against HCoV-NL63 in a cell-type independent manner. The results specify that tryptanthrin possesses antiviral potential against HCoV-NL63 infection. On 31 December, 2019, a cluster of 27 pneumonia cases of unknown etiology was reported by Chinese health authorities in Wuhan City (China) [...]",2020,"Tsai, Yu-Chi; Lee, Chia-Lin; Yen, Hung-Rong; Chang, Young-Sheng; Lin, Yu-Ping; Huang, Su-Hua; Lin, Cheng-Wen; Amodio, Emanuele; Vitale, Francesco; Cimino, Livia; Casuccio, Alessandra; Tramuto, Fabio",Biomolecules,2977112956,#2528,
,CZI,Advance in human coronaviruses research of host interactions,10.3390/diseases4030026,,,,"2019-novel coronavirus (2019-nCoV) is a highly pathogenic human CoV that first emerged in Wuhan in 2019.2019-nCoV has a zoonotic origin and poses a major threat to public health.However, little is known about the viral factors contributing to the high virulence of 2019-nCoV.Many animal viruses, including CoVs, encode proteins that interfere with host gene expression, including those involved in antiviral immune responses, and these viral proteins are often major virulence factors.Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory infection.In the past 17 years, the onset of 2019-nCoV, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans.The recent study of HCoVs-host interactions has contributed extensively to our understanding of infection pathogenesis of 2019-nCoV.This review discuss various host physiopathologic mechanism, such as apoptosis, innate immunity, endoplasmic reticulum (ER) stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-&kappa;B) pathway that may be modulated by HCoVs and provides evidence for the intensive investigate of 2019-nCoV infection.",2020,"GU, Yanni; SHEN, Chaobin; CHEN, Tongxin",Chinese Journal of Applied Clinical Pediatrics,2491014331,#2275,
,CZI,"On the Coronavirus (COVID-19) Outbreak and the Smart City Network: Universal Data Sharing Standards Coupled with Artificial Intelligence (AI) to Benefit Urban Health Monitoring and Management Epidemiological Identification of A Novel Pathogen in Real Time: Analysis of the Atypical Pneumonia Outbreak in Wuhan, China, 2019—2020",10.3390/healthcare8010046ER - Y - EJOU 10.3390/jcm9030637ER -,,,,"As the Coronavirus (COVID-19) expands its impact from China, expanding its catchment into surrounding regions and other countries, increased national and international measures are being taken to contain the outbreak. The placing of entire cities in &lsquo;lockdown&rsquo; directly affects urban economies on a multi-lateral level, including from social and economic standpoints. This is being emphasised as the outbreak gains ground in other countries, leading towards a global health emergency, and as global collaboration is sought in numerous quarters. However, while effective protocols in regard to the sharing of health data is emphasised, urban data, on the other hand, specifically relating to urban health and safe city concepts, is still viewed from a nationalist perspective as solely benefiting a nation&rsquo;s economy and its economic and political influence. This perspective paper, written one month after detection and during the outbreak, surveys the virus outbreak from an urban standpoint and advances how smart city networks should work towards enhancing standardization protocols for increased data sharing in the event of outbreaks or disasters, leading to better global understanding and management of the same. Virological tests have now shown conclusively that a novel coronavirus is causing the 2019&ndash;2020 atypical pneumonia outbreak in Wuhan, China. We demonstrate that non-virological descriptive characteristics could have determined that the outbreak is caused by a novel pathogen in advance of virological testing. Characteristics of the ongoing outbreak were collected in real time from two medical social media sites. These were compared against characteristics of eleven pathogens that have previously caused cases of atypical pneumonia. The probability that the current outbreak is due to &ldquo;Disease X&rdquo; (i.e., previously unknown etiology) as opposed to one of the known pathogens was inferred, and this estimate was updated as the outbreak continued. The probability (expressed as a percentage) that Disease X is driving the outbreak was assessed as over 29% on 31 December 2019, one week before virus identification. After some specific pathogens were ruled out by laboratory tests on 5 January 2020, the inferred probability of Disease X was over 49%. We showed quantitatively that the emerging outbreak of atypical pneumonia cases is consistent with causation by a novel pathogen. The proposed approach, which uses only routinely observed non-virological data, can aid ongoing risk assessments in advance of virological test results becoming available.",2020,"Allam, Zaheer; Jones, David S.; Jung, Sung-mok; Kinoshita, Ryo; Thompson, N. Robin; Linton, M. Natalie; Yang, Yichi; Akhmetzhanov, R. Andrei; Nishiura, Hiroshi",Healthcare,,#2685,
,CZI,Prediction of Epidemic Spread of the 2019 Novel Coronavirus Driven by Spring Festival Transportation in China: A Population-Based Study,10.3390/ijerph17051679,,,,"After the 2019 novel coronavirus (2019-nCoV) outbreak, we estimated the distribution and scale of more than 5 million migrants residing in Wuhan after they returned to their hometown communities in Hubei Province or other provinces at the end of 2019 by using the data from the 2013&ndash;2018 China Migrants Dynamic Survey (CMDS). We found that the distribution of Wuhan&rsquo;s migrants is centred in Hubei Province (approximately 75%) at a provincial level, gradually decreasing in the surrounding provinces in layers, with obvious spatial characteristics of circle layers and echelons. The scale of Wuhan&rsquo;s migrants, whose origins in Hubei Province give rise to a gradient reduction from east to west within the province, and account for 66% of Wuhan&rsquo;s total migrants, are from the surrounding prefectural-level cities of Wuhan. The distribution comprises 94 districts and counties in Hubei Province, and the cumulative percentage of the top 30 districts and counties exceeds 80%. Wuhan&rsquo;s migrants have a large proportion of middle-aged and high-risk individuals. Their social characteristics include nuclear family migration (84%), migration with families of 3&ndash;4 members (71%), a rural household registration (85%), and working or doing business (84%) as the main reason for migration. Using a quasi-experimental analysis framework, we found that the size of Wuhan&rsquo;s migrants was highly correlated with the daily number of confirmed cases. Furthermore, we compared the epidemic situation in different regions and found that the number of confirmed cases in some provinces and cities in Hubei Province may be underestimated, while the epidemic situation in some regions has increased rapidly. The results are conducive to monitoring the epidemic prevention and control in various regions.",2020,"Fan, Changyu; Liu, Linping; Guo, Wei; Yang, Anuo; Ye, Chenchen; Jilili, Maitixirepu; Ren, Meina; Xu, Peng; Long, Hexing; Wang, Yufan",International Journal of Environmental Research and Public Health,3002747665,#4088,
,CZI,Immediate Psychological Responses and Associated Factors during the Initial Stage of the 2019 Coronavirus Disease (COVID-19) Epidemic among the General Population in China,10.3390/ijerph17051729,,,,"Background: The 2019 coronavirus disease (COVID-19) epidemic is a public health emergency of international concern and poses a challenge to psychological resilience. Research data are needed to develop evidence-driven strategies to reduce adverse psychological impacts and psychiatric symptoms during the epidemic. The aim of this study was to survey the general public in China to better understand their levels of psychological impact, anxiety, depression, and stress during the initial stage of the COVID-19 outbreak. The data will be used for future reference. Methods: From 31 January to 2 February 2020, we conducted an online survey using snowball sampling techniques. The online survey collected information on demographic data, physical symptoms in the past 14 days, contact history with COVID-19, knowledge and concerns about COVID-19, precautionary measures against COVID-19, and additional information required with respect to COVID-19. Psychological impact was assessed by the Impact of Event Scale-Revised (IES-R), and mental health status was assessed by the Depression, Anxiety and Stress Scale (DASS-21). Results: This study included 1210 respondents from 194 cities in China. In total, 53.8% of respondents rated the psychological impact of the outbreak as moderate or severe; 16.5% reported moderate to severe depressive symptoms; 28.8% reported moderate to severe anxiety symptoms; and 8.1% reported moderate to severe stress levels. Most respondents spent 20&ndash;24 h per day at home (84.7%); were worried about their family members contracting COVID-19 (75.2%); and were satisfied with the amount of health information available (75.1%). Female gender, student status, specific physical symptoms (e.g., myalgia, dizziness, coryza), and poor self-rated health status were significantly associated with a greater psychological impact of the outbreak and higher levels of stress, anxiety, and depression (p &lt; 0.05). Specific up-to-date and accurate health information (e.g., treatment, local outbreak situation) and particular precautionary measures (e.g., hand hygiene, wearing a mask) were associated with a lower psychological impact of the outbreak and lower levels of stress, anxiety, and depression (p &lt; 0.05). Conclusions: During the initial phase of the COVID-19 outbreak in China, more than half of the respondents rated the psychological impact as moderate-to-severe, and about one-third reported moderate-to-severe anxiety. Our findings identify factors associated with a lower level of psychological impact and better mental health status that can be used to formulate psychological interventions to improve the mental health of vulnerable groups during the COVID-19 epidemic.",2020,"Wang, Cuiyan; Pan, Riyu; Wan, Xiaoyang; Tan, Yilin; Xu, Linkang; Ho, S. Cyrus; Ho, C. Roger",International Journal of Environmental Research and Public Health,1994584686,#5504,
,CZI,A Meta-Analysis of Multiple Whole Blood Gene Expression Data Unveils a Diagnostic Host-Response Transcript Signature for Respiratory Syncytial Virus,10.3390/ijms21051831ER -,,,,"Respiratory syncytial virus (RSV) is one of the major causes of acute lower respiratory tract infection worldwide. The absence of a commercial vaccine and the limited success of current therapeutic strategies against RSV make further research necessary. We used a multi-cohort analysis approach to investigate host transcriptomic biomarkers and shed further light on the molecular mechanism underlying RSV-host interactions. We meta-analyzed seven transcriptome microarray studies from the public Gene Expression Omnibus (GEO) repository containing a total of 922 samples, including RSV, healthy controls, coronaviruses, enteroviruses, influenzas, rhinoviruses, and coinfections, from both adult and pediatric patients. We identified &gt; 1500 genes differentially expressed when comparing the transcriptomes of RSV-infected patients against healthy controls. Functional enrichment analysis showed several pathways significantly altered, including immunologic response mediated by RSV infection, pattern recognition receptors, cell cycle, and olfactory signaling. In addition, we identified a minimal 17-transcript host signature specific for RSV infection by comparing transcriptomic profiles against other respiratory viruses. These multi-genic signatures might help to investigate future drug targets against RSV infection.",2020,"Barral-Arca, Ruth; Gómez-Carballa, Alberto; Cebey-López, Miriam; Bello, Xabier; Martinón-Torres, Federico; Salas, Antonio",International Journal of Molecular Sciences,2794338276,#5053,
,CZI,"Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak Risk Management Analysis for Novel Coronavirus in Wuhan, China",10.3390/jcm9020388 10.3390/jrfm13020022,,,,"Background: In December 2019, an outbreak of respiratory illness caused by a novel coronavirus (2019-nCoV) emerged in Wuhan, China and has swiftly spread to other parts of China and a number of foreign countries. The 2019-nCoV cases might have been under-reported roughly from 1 to 15 January 2020, and thus we estimated the number of unreported cases and the basic reproduction number, R0, of 2019-nCoV. Methods: We modelled the epidemic curve of 2019-nCoV cases, in mainland China from 1 December 2019 to 24 January 2020 through the exponential growth. The number of unreported cases was determined by the maximum likelihood estimation. We used the serial intervals (SI) of infection caused by two other well-known coronaviruses (CoV), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) CoVs, as approximations of the unknown SI for 2019-nCoV to estimate R0. Results: We confirmed that the initial growth phase followed an exponential growth pattern. The under-reporting was likely to have resulted in 469 (95% CI: 403&minus;540) unreported cases from 1 to 15 January 2020. The reporting rate after 17 January 2020 was likely to have increased 21-fold (95% CI: 18&minus;25) in comparison to the situation from 1 to 17 January 2020 on average. We estimated the R0 of 2019-nCoV at 2.56 (95% CI: 2.49&minus;2.63). Conclusion: The under-reporting was likely to have occurred during the first half of January 2020 and should be considered in future investigation. Recently, a novel coronavirus pneumonia (2019&ndash;nCoV) outbreak occurred in Wuhan, China, rapidly spreading first to the whole country, and then globally, causing widespread concern. From the perspectives of early warning and identification of risk, risk monitoring, and analysis, as well as risk management and handling, we propose corresponding solutions and recommendations, which include institutional cooperation, and to inform national and international policy-makers.",2020,"Zhao, Shi; Musa, Salihu S.; Lin, Qianying; Ran, Jinjun; Yang, Guangpu; Wang, Weiming; Lou, Yijun; Yang, Lin; Gao, Daozhou; He, Daihai; Wang, Maggie H.; Yue, Xiao-Guang; Shao, Xue-Feng; Li, Y. Rita; Crabbe, James C. M.; Mi, Lili; Hu, Siyan; Baker, S. Julien; Liang, Gang",Journal of Clinical Medicine,3004200727,#158,
,CZI,The report of two cases infection with novel coronavirus (2019-ncov) after kidney transplantation and the association literature analyzation,10.3390/jcm9020419,,,,"Objective To investigate the clinical experience of patients with novel coronavirus (2019-ncov) infection after kidney transplantation. Method Clinical data of two patients with 2019-nCoV infection after renal transplantationin Jan 2020 Renmin Hospital of Wuhan Universiyt were retrospectively analyzed.Case 1 was a 48-year-old male with CMV pneumonia secondary to 2019-nCoV infection at 4 months after transplantation. CT imaging showed multiple patchy ground-glass images of both lungs. Case 2 was a 59-year-old male, who was screened positive for 2019-nCoV nucleic acid due to fever at 9 days after renal transplantation and showed no clinical manifestations of pneumonia. After diagnosis, case 1 was transferred to a designated hospital for isolation. Treatment regimens: cefoperazone sulbactam sodium + linezolid to resist infection, gamma globulin to enhance immunity function, methylprednisolone to control inflammatory response, antiviral regimens including arbidol tablets + lopina-velitonavir tablets. Case 2 was treated with isolated treatment in a single room. The treatment plan included anti-infection (cefoperazone sulbactam sodium), enhancing immunity function (gamma globulin), antivirus therapy with arbidol and other symptomatic treatment. Result Follow up with 3 weeks, case 1 recovered with renal dysfunction, nucleic acid test with nasopharyngeal swabs turned negative, and pulmonary imaging improved. Case 2 showed no obvious clinical symptoms, and the nucleic acid test of nasopharyngeal swabs turned negative for 3 times. Conclusion Renal transplant recipients should receive fine protection to avoid exposure to high-risk environments. Diagnosis should be defined with combination of clinical manifestations, nucleic acid test and pulmonary imaging. At present, there are no antiviral drugs and symptomatic treatment is the main choice.",2020,"QIU, Tao; WANG, Jingyue; ZHOU, Jiangqiao; ZOU, Jilin; CHEN, Zhongbao; MA, Xiaoxiong; ZHANG, Long",Chinese Journal of Organ Transplantation,3004658686,#2425,
,CZI,"Initial Cluster of Novel Coronavirus (2019-nCoV) Infections in Wuhan, China Is Consistent with Substantial Human-to-Human Transmission Novel Coronavirus Outbreak in Wuhan, China, 2020: Intense Surveillance Is Vital for Preventing Sustained Transmission in New Locations",10.3390/jcm9020488 10.3390/jcm9020498ER -,,,,"Reanalysis of the epidemic curve from the initial cluster of cases with novel coronavirus (2019-nCoV) in December 2019 indicates substantial human-to-human transmission. It is possible that the common exposure history at a seafood market in Wuhan originated from the human-to-human transmission events within the market, and the early, strong emphasis that market exposure indicated animal-to-human transmission was potentially the result of observer bias. To support the hypothesis of zoonotic origin of 2019-nCoV stemming from the Huanan seafood market, the index case should have had exposure history related to the market and the virus should have been identified from animals sold at the market. As these requirements remain unmet, zoonotic spillover at the market must not be overemphasized. The outbreak of pneumonia originating in Wuhan, China, has generated 24,500 confirmed cases, including 492 deaths, as of 5 February 2020. The virus (2019-nCoV) has spread elsewhere in China and to 24 countries, including South Korea, Thailand, Japan and USA. Fortunately, there has only been limited human-to-human transmission outside of China. Here, we assess the risk of sustained transmission whenever the coronavirus arrives in other countries. Data describing the times from symptom onset to hospitalisation for 47 patients infected early in the current outbreak are used to generate an estimate for the probability that an imported case is followed by sustained human-to-human transmission. Under the assumptions that the imported case is representative of the patients in China, and that the 2019-nCoV is similarly transmissible to the SARS coronavirus, the probability that an imported case is followed by sustained human-to-human transmission is 0.41 (credible interval [0.27, 0.55]). However, if the mean time from symptom onset to hospitalisation can be halved by intense surveillance, then the probability that an imported case leads to sustained transmission is only 0.012 (credible interval [0, 0.099]). This emphasises the importance of current surveillance efforts in countries around the world, to ensure that the ongoing outbreak will not become a global pandemic.",2020,"Nishiura, Hiroshi; Linton, Natalie M.; Akhmetzhanov, Andrei R.; Thompson, Robin N.",Journal of Clinical Medicine,3005599914,#667,
,CZI,Risk Assessment of Novel Coronavirus COVID-19 Outbreaks Outside China,10.3390/jcm9020571,,,,"We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination; and (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number R loc ). We found that in countries with low connectivity to China but with relatively high R loc , the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low R loc benefit the most from policies that further reduce R loc . Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia, and Europe. We investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing.",2020,"Boldog, Péter; Tekeli, Tamás; Vizi, Zsolt; Dénes, Attila; Bartha, Ferenc A.; Röst, Gergely",Journal of Clinical Medicine,3005847234,#1328,
,CZI,Risk Assessment of Novel Coronavirus COVID-19 Outbreaks Outside China Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China,10.3390/jcm9020571 10.3390/jcm9020575ER -,,,,"We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination; and (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number R loc ). We found that in countries with low connectivity to China but with relatively high R loc , the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low R loc benefit the most from policies that further reduce R loc . Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia, and Europe. We investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing. In December 2019, cases of unidentified pneumonia with a history of exposure in the Huanan Seafood Market were reported in Wuhan, Hubei Province. A novel coronavirus, SARS-CoV-2, was identified to be accountable for this disease. Human-to-human transmission is confirmed, and this disease (named COVID-19 by World Health Organization (WHO)) spread rapidly around the country and the world. As of 18 February 2020, the number of confirmed cases had reached 75,199 with 2009 fatalities. The COVID-19 resulted in a much lower case-fatality rate (about 2.67%) among the confirmed cases, compared with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Among the symptom composition of the 45 fatality cases collected from the released official reports, the top four are fever, cough, short of breath, and chest tightness/pain. The major comorbidities of the fatality cases include hypertension, diabetes, coronary heart disease, cerebral infarction, and chronic bronchitis. The source of the virus and the pathogenesis of this disease are still unconfirmed. No specific therapeutic drug has been found. The Chinese Government has initiated a level-1 public health response to prevent the spread of the disease. Meanwhile, it is also crucial to speed up the development of vaccines and drugs for treatment, which will enable us to defeat COVID-19 as soon as possible.",2020,"Boldog, Péter; Tekeli, Tamás; Vizi, Zsolt; Dénes, Attila; Bartha, A. Ferenc; Röst, Gergely; Deng, Sheng-Qun; Peng, Hong-Juan",Journal of Clinical Medicine,3005347918,#1688,
,CZI,Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess Comparative Seasonal Respiratory Virus Epidemic Timing in Utah,10.3390/jcm9030657 10.3390/v12030275,,,,"To understand the time-dependent risk of infection on a cruise ship, the Diamond Princess, I estimated the incidence of infection with novel coronavirus (COVID-19). The epidemic curve of a total of 199 confirmed cases was drawn, classifying individuals into passengers with and without close contact and crew members. A backcalculation method was employed to estimate the incidence of infection. The peak time of infection was seen for the time period from 2 to 4 February 2020, and the incidence has abruptly declined afterwards. The estimated number of new infections among passengers without close contact was very small from 5 February on which a movement restriction policy was imposed. Without the intervention from 5 February, it was predicted that the cumulative incidence with and without close contact would have been as large as 1373 (95% CI: 570, 2176) and 766 (95% CI: 587, 946) cases, respectively, while these were kept to be 102 and 47 cases, respectively. Based on an analysis of illness onset data on board, the risk of infection among passengers without close contact was considered to be very limited. Movement restriction greatly reduced the number of infections from 5 February onwards. Previous studies have found evidence of viral interference between seasonal respiratory viruses. Using laboratory-confirmed data from a Utah-based healthcare provider, Intermountain Health Care, we analyzed the time-specific patterns of respiratory syncytial virus (RSV), influenza A, influenza B, human metapneumovirus, rhinovirus, and enterovirus circulation from 2004 to 2018, using descriptive methods and wavelet analysis (n = 89,462) on a local level. The results showed that RSV virus dynamics in Utah were the most consistent of any of the viruses studied, and that the other seasonal viruses were generally in synchrony with RSV, except for enterovirus (which mostly occurs late summer to early fall) and influenza A and B during pandemic years.",2020,"Nishiura, Hiroshi; Callahan, Y. Zayne; Smith, K. Trevor; Ingersoll, Celeste; Gardner, Rebecca; Korgenski, K. E.; Sloan, D. Chantel",Journal of Clinical Medicine,2026628614,#2906,
,CZI,Optimization Method for Forecasting Confirmed Cases of COVID-19 in China Prevention Is Better Than the Cure: Risk Management of COVID-19 Synthesis and Bioactivity Assessment of Novel Spiro Pyrazole-Oxindole Congeners Exhibiting Potent and Selective in vitro Anticancer Effects,10.3390/jcm9030674 10.3390/jrfm13030046 10.3390/molecules25051124ER -,,,,"In December 2019, a novel coronavirus, called COVID-19, was discovered in Wuhan, China, and has spread to different cities in China as well as to 24 other countries. The number of confirmed cases is increasing daily and reached 34,598 on 8 February 2020. In the current study, we present a new forecasting model to estimate and forecast the number of confirmed cases of COVID-19 in the upcoming ten days based on the previously confirmed cases recorded in China. The proposed model is an improved adaptive neuro-fuzzy inference system (ANFIS) using an enhanced flower pollination algorithm (FPA) by using the salp swarm algorithm (SSA). In general, SSA is employed to improve FPA to avoid its drawbacks (i.e., getting trapped at the local optima). The main idea of the proposed model, called FPASSA-ANFIS, is to improve the performance of ANFIS by determining the parameters of ANFIS using FPASSA. The FPASSA-ANFIS model is evaluated using the World Health Organization (WHO) official data of the outbreak of the COVID-19 to forecast the confirmed cases of the upcoming ten days. More so, the FPASSA-ANFIS model is compared to several existing models, and it showed better performance in terms of Mean Absolute Percentage Error (MAPE), Root Mean Squared Relative Error (RMSRE), Root Mean Squared Relative Error (RMSRE), coefficient of determination ( R 2 ), and computing time. Furthermore, we tested the proposed model using two different datasets of weekly influenza confirmed cases in two countries, namely the USA and China. The outcomes also showed good performances. A novel coronavirus was reported to the World Health Organization (WHO) in China on 31 December 2019. The WHO named the disease COVID-19 on 11 February 2020. As of 26 February 2020, the disease has been detected on all continents, except for Antarctica. Daily updates on COVID-19 since early February 2020 have made headline news worldwide for much of 2020. This editorial evaluates risk management based on the Global Health Security (GHS) Index of global health security capabilities in 195 countries. The GHS Index lists the countries best prepared for an epidemic or pandemic. COVID-19 is compared with two related coronavirus epidemics, SARS and MERS, in terms of the number of reported human infections, deaths, countries, major country clusters, timelines, and the likelihood of discovering a safe, effective, and approved vaccine. The present work aims to design and synthesize novel series of spiro pyrazole-3,3&rsquo;-oxindoles analogues and investigate their bioactivity as antioxidant and antimicrobial agents, as well as antiproliferative potency against selected human cancerous cell lines (i.e., breast, MCF-7; colon, HCT-116 and liver, HepG-2) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and proapoptotic protein markers. The analytical and spectral data of the all synthesized target congeners were compatible with their structures. Synthesized compounds showed diverse moderate to powerful antimicrobial and antioxidant activities. Results of MTT assay revealed that seven synthesized compounds (i.e., 11a, 11b, 12a, 12b, 13b, 13c and 13h) particularly exhibited significant cytotoxicity against the three cancerous cell lines under investigation. Ranges of IC50 values obtained were 5.7&ndash;21.3 and 5.8&ndash;37.4 &micro;g/mL against HCT-116 and MCF-7, respectively; which is 3.8 and 6.5-fold (based on the least IC50 values) more significant relative to the reference chemotherapeutic drug doxorubicin. In HepG-2 cells, the analogue 13h the highest cytotoxicity with IC50 value of 19.2&micro;g/mL relative to doxorubicin (IC50 = 21.6&micro;g/mL). The observed cytotoxicity was specific to cancerous cells, as evidenced by the minimal toxicity in the noncancerous control skin-fibroblast cells. ELISA results indicated that the observed antiproliferative effect against examined cancer cell lines is mediated via engaging the activation of apoptosis as illustrated by the significant increase in proapoptotic protein markers (p53, bax and caspase-3) and reduction in the antiapoptotic marker bcl-2. Taken together, results of the present study emphasize the potential of spiro pyrazole-oxindole analogues as valuable candidate anticancer agents against human cancer cells.",2020,"Al-qaness, A. A. Mohammed; Ewees , A. Ahmed; Fan, Hong; Abd El Aziz , Mohamed; McAleer, Michael; Abo-Salem, M. Heba; Nassrallah, Amr; Soliman, A. F. Ahmed; Ebied, S. Manal; Elawady, E. Mohamed; Abdelhamid, A. Sayeda; El-Sawy, R. Eslam; Al-Sheikh, A. Yazeed; Aboul-Soud, A. M. Mourad",Journal of Clinical Medicine,3006671704,#3465,
,CZI,Risk Management of COVID-19 by Universities in China,10.3390/jrfm13020036,,,,"The rapid spread of new coronaviruses throughout China and the world in 2019&ndash;2020 has had a great impact on China&rsquo;s economic and social development. As the backbone of Chinese society, Chinese universities have made significant contributions to emergency risk management. Such contributions have been made primarily in the following areas: alumni resource collection, medical rescue and emergency management, mental health maintenance, control of staff mobility, and innovation in online education models. Through the support of these methods, Chinese universities have played a positive role in the prevention and control of the epidemic situation. However, they also face the problems of alumni&rsquo;s economic development difficulties, the risk of deadly infection to medical rescue teams and health workers, infection of teachers and students, and the unsatisfactory application of information technology in resolving the crisis. In response to these risks and emergency problems, we propose some corresponding solutions for public dissemination, including issues related to medical security, emergency research, professional assistance, positive communication, and hierarchical information-based teaching.",2020,"Wang, Chuanyi; Cheng, Zhe; Yue, Xiao-Guang; McAleer, Michael",Journal of Risk and Financial Management,2084356930,#1265,
,CZI,"Risk Management of COVID-19 by Universities in China Short-term Forecasts of the COVID-19 Epidemic in Guangdong and Zhejiang, China: February 13–23, 2020",10.3390/jrfm13020036 ERT - Y - EJOU 10.3390/jcm9020596,,,,"The rapid spread of new coronaviruses throughout China and the world in 2019&ndash;2020 has had a great impact on China&rsquo;s economic and social development. As the backbone of Chinese society, Chinese universities have made significant contributions to emergency risk management. Such contributions have been made primarily in the following areas: alumni resource collection, medical rescue and emergency management, mental health maintenance, control of staff mobility, and innovation in online education models. Through the support of these methods, Chinese universities have played a positive role in the prevention and control of the epidemic situation. However, they also face the problems of alumni&rsquo;s economic development difficulties, the risk of deadly infection to medical rescue teams and health workers, infection of teachers and students, and the unsatisfactory application of information technology in resolving the crisis. In response to these risks and emergency problems, we propose some corresponding solutions for public dissemination, including issues related to medical security, emergency research, professional assistance, positive communication, and hierarchical information-based teaching. The ongoing COVID-19 epidemic continues to spread within and outside of China, despite several social distancing measures implemented by the Chinese government. Limited epidemiological data are available, and recent changes in case definition and reporting further complicate our understanding of the impact of the epidemic, particularly in the epidemic&rsquo;s epicenter. Here we use previously validated phenomenological models to generate short-term forecasts of cumulative reported cases in Guangdong and Zhejiang, China. Using daily reported cumulative case data up until 13 February 2020 from the National Health Commission of China, we report 5- and 10-day ahead forecasts of cumulative case reports. Specifically, we generate forecasts using a generalized logistic growth model, the Richards growth model, and a sub-epidemic wave model, which have each been previously used to forecast outbreaks due to different infectious diseases. Forecasts from each of the models suggest the outbreaks may be nearing extinction in both Guangdong and Zhejiang; however, the sub-epidemic model predictions also include the potential for further sustained transmission, particularly in Zhejiang. Our 10-day forecasts across the three models predict an additional 65&ndash;81 cases (upper bounds: 169&ndash;507) in Guangdong and an additional 44&ndash;354 (upper bounds: 141&ndash;875) cases in Zhejiang by February 23, 2020. In the best-case scenario, current data suggest that transmission in both provinces is slowing down.",2020,"Wang, Chuanyi; Cheng, Zhe; Yue, Xiao-Guang; McAleer, Michael; Roosa, Kimberlyn; Lee, Yiseul; Luo, Ruiyan; Kirpich, Alexander; Rothenberg, Richard; Hyman, M. James; Yan, Ping; Chowell, Gerardo",Journal of Risk and Financial Management,,#1751,
,CZI,Host Factors Affecting Generation of Immunity Against Porcine Epidemic Diarrhea Virus in Pregnant and Lactating Swine and Passive Protection of Neonates,10.3390/pathogens9020130,,,,"Porcine epidemic diarrhea virus (PEDV) is a highly virulent re-emerging enteric coronavirus that causes acute diarrhea, dehydration, and up to 100% mortality in neonatal suckling piglets. Despite this, a safe and effective PEDV vaccine against highly virulent strains is unavailable, making PEDV prevention and control challenging. Lactogenic immunity induced via the gut-mammary gland-secretory IgA (sIgA) axis, remains the most promising and effective way to protect suckling piglets from PEDV. Therefore, a successful PEDV vaccine must induce protective maternal IgA antibodies that passively transfer into colostrum and milk. Identifying variables that influence lymphocyte migration and IgA secretion during gestation and lactation is imperative for designing maternal immunization strategies that generate the highest amount of lactogenic immune protection against PEDV in suckling piglets. Because pregnancy-associated immune alterations influence viral pathogenesis and adaptive immune responses in many different species, a better understanding of host immune responses to PEDV in pregnant swine may translate into improved maternal immunization strategies against enteric pathogens for multiple species. In this review, we discuss the role of host factors during pregnancy on antiviral immunity and their implications for generating protective lactogenic immunity in suckling neonates.",2020,"Langel, Stephanie N.; Wang, Qiuhong; Vlasova, Anastasia N.; Saif, Linda J.",Pathogens,2797271523,#1292,
,CZI,Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks,10.3390/pathogens9030186ER -,,,,"Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. The continuous evolution of coronaviruses was further highlighted with the emergence of the Middle East Respiratory Syndrome-CoV (MERS-CoV) outbreak in 2012. Currently, the world is concerned about the 2019 novel CoV (SARS-CoV-2) that was initially identified in the city of Wuhan, China in December 2019. Patients presented with severe viral pneumonia and respiratory illness. The number of cases has been mounting since then. As of late February 2020, tens of thousands of cases and several thousand deaths have been reported in China alone, in addition to thousands of cases in other countries. Although the fatality rate of SARS-CoV-2 is currently lower than SARS-CoV, the virus seems to be highly contagious based on the number of infected cases to date. In this review, we discuss structure, genome organization, entry of CoVs into target cells, and provide insights into past and present outbreaks. The future of human CoV outbreaks will not only depend on how the viruses will evolve, but will also depend on how we develop efficient prevention and treatment strategies to deal with this continuous threat.",2020,"Ashour, M. Hossam; Elkhatib, F. Walid; Rahman, M. Md; Elshabrawy, A. Hatem",Pathogens,3006050861,#3521,
,CZI,Chemotherapy strategy for colorectal cancer under the outbreak of novel coronavirus pneumonia,10.3760/cma.j.cn.441530-20200226-00093,,32100980,,"The outbreak of novel coronavirus pneumonia (NCP) makes the medical treatment of colorectal cancers difficult. Cancer patients are more susceptible to infection and tumor history is defined as an important factor of poor prognosis, which challenges both doctors and patients. For metastatic colorectal cancer (CRC) patients, maintenance therapy is the optimal choice. The patients with tumor progression or poor biological behaviorshould receive or or continue combination chemotherapy. Adjuvant chemotherapy should reduce the intensity of treatment and shorten the therapy time. Fever patients during chemotherapy need to receive differential diagnosis and screening according to national standards. Patients with stable diseases and good general conditions may delay imaging examination.. Clinicians should make individual clinical decisions based on the specifics of each patient durding epidemic situation.",2020,"Li, Y. H.; Shen, L.; Li, J.",Zhonghua Wei Chang Wai Ke Za Zhi,1970973591,#2200,
,CZI,Analysis of low positive rate of nucleic acid detection method used for diagnosis of novel coronavirus pneumonia,10.3760/cma.j.cn112137-20200213-00280,,32077662,,,2020,"Wang, C. B.",Zhonghua Yi Xue Za Zhi,1831268804,#1472,
,CZI,[Consideration and suggestions on development of blood transfusion department under the epidemic situation of novel coronavirus pneumonia],10.3760/cma.j.cn112137-20200221-00387,,32108458,,,2020,"Liu, X. M.; Wang, D. Q.",Zhonghua yi xue za zhi,2383858113,#2888,
,CZI,Strengthen comprehensive strategies to treat patients with mild novel coronavirus pneumonia,10.3760/cma.j.cn112138-20200217-00083,,32090534,,,2020,"Jia, W. P.",Zhonghua Nei Ke Za Zhi,3004071935,#1831,
,CZI,Drug interaction monitoring of lopinavir / ritonavir in COVID-19 patients with cancer,10.3760/cma.j.cn112138-20200219-00097,,32114746,,,2020,"Zheng, X. W.; Tao, G.; Zhang, Y. W.; Yang, G. N.; Huang, P.",Zhonghua Nei Ke Za Zhi,1480085725,#3042,
,CZI,[Treatment strategies of Budd-Chiari syndrome during the epidemic period of 2019 coronavirus disease],10.3760/cma.j.cn112139-20200221-00109,,32108459,,"Prevention and control about the situation of 2019 coronavirus disease (COVID-19) are grim at present. In addition to supporting the frontline actively, medical workers in general surgery spare no efforts in making good diagnosis and treatment of specialized diseases by optimizing treatment process, providing medical advice online, mastering indications of delayed operation and emergency operation reasonably, etc. Budd-Chiari syndrome is a complex disorder, and severity of the disease varies, serious cases can be life threatening. While fighting the epidemic, medical workers should also ensure the medical needs of patients. However, instead of continuing the traditional treatment, a new management system should be developed. Based on the characteristics of Budd-Chiari syndrome patients in China and our experience, we divide the patients into ordinary and critical cases, and treatment strategies suitable for the epidemic period of COVID-19 are put forward for reference and discussion by physicians.",2020,"Li, L. H.; Zhang, G.; Dang, X. W.; Li, L.",Zhonghua wai ke za zhi [Chinese journal of surgery],2935897573,#2872,
,CZI,The treatment proposal for the patients with breast diseases in the central epidemic area of 2019 coronavirus disease,10.3760/cma.j.cn112139-20200221-00116,,32096395,,"Currently, the epidemic of 2019 coronavirus disease (COVID-19) is still ongoing. The characteristics including high contagiousness, herd susceptibility and clinical phenotype diversity, made a serious influence on people's daily life and rountine therapy for other diseases. Breast dieases are clinical common diseases. In the central epidemic area of COVID-19, Hubei province, especially Wuhan, the clinical specialists of breast diseases should consider all of the following factors comprehensively: the prevention of COVID-19, the diagnosis and treatment of breast diseases and the accessibility of medical resources. Besides, we should select the appropriate therapy and optimize treatment process so as to prevent the propagation and cross infection of COVID-19 as well as manage the breast diseases without delay. Therefore, we carried out some management proposals of the patients with breast diseases in the central epidemic area during the epidemic of COVID-19 on the basis of conventional treatment guidelines and clinical experiences. The suggestions and corrections from colleagues will be welcomed.",2020,"Zhao, L.; Zhang, L.; Liu, J. W.; Yang, Z. F.; Shen, W. Z.; Li, X. R.",Zhonghua Wai Ke Za Zhi,2130735457,#1890,
,CZI,[Treatment of pancreatic diseases and prevention of infection during outbreak of 2019 coronavirus disease],10.3760/cma.j.cn112139-20200224-00123,,32107909,,"Objective: To explorethe proper protective measures for pancreaticdiseases treatment during theoutbreak of 2019 coronavirus disease(COVID-19). Method: Clinical data of four cases of patients that suffered COVID-19from February 2(nd), 2020 to February 9(th), 2020 in pancreatic surgery were reviewed.After the first patientscuffednosocomial infection of COVID-19, the general protective measures in our department wereupdated.Only one patient was admitted to each room alone, with no more than one caregiver.The body temperature of care givers was measuredtwice a day.Primary protections were applied to all staff.The floor was sterilized using disinfectant with an effective chlorine concentration of 1000 mg/L.The protective measures for interventional procedures were as follow.Primary protection was applied to the operators ofcentral venipuncture catheter, percutaneous abdominal/pleural drainage, percutaneous retroperitoneal drainage, percutaneous transhepatic cholangial drainage and other surgical procedures with local anesthesiaand epidural anesthesia.Secondary protection was applied to the operators of endoscopic retrograde cholangiopancreatography and surgical procedures with general anesthesia. Results: During Feb 2(nd), 2020 to Feb 9(th), 2020, four patients in our department were diagnosed with COVID-19, of which one was died of COVID-19, two were cured, and one is still in hospital for COVID-19.After the update ofprotective measures in our department, no more nosocomial infection of COVID-19occurred.Two central venipuncture catheter, three percutaneous abdominal/pleural drainage, one percutaneous retroperitoneal drainage, one percuteneous transhepatic cholecyst drainage and one open surgery with general anesthesia were performed with no infection of operators. Conclusions: The caregivers of patients are potential infection source of COVID-19.Enhanced protective measures including the management measures of caregivers can decrease the risk of nosocomial infection of COVID-19.",2020,"Gou, S. M.; Yin, T.; Xiong, J. X.; Peng, T.; Li, Y.; Wu, H. S.",Zhonghua wai ke za zhi [Chinese journal of surgery],3004896587,#2819,
,CZI,Clinical analysis of 31 cases of 2019 novel coronavirus infection in children from six provinces (autonomous region) of northern China,10.3760/cma.j.cn112140-20200225-00138,,32118389,,"Objective: To analyze the epidemiological history, clinical manifestations, treatment and the short-term prognosis of 31 cases of 2019 novel coronavirus(2019-nCoV) infection in children from six provinces (autonomous region) in northern China. Methods: A retrospective analysis of the epidemiological history, clinical symptoms, signs, laboratory examinations, chest imaging, treatment and the short-term prognosis of 31 cases of 2019-nCoV was conducted. The patients were diagnosed between January 25th, 2020 and February 21st, 2020 in 21 hospitals in 17 cities of six provinces(autonomous region) of Shaanxi, Gansu, Ningxia, Hebei, Henan and Shandong. Results: The age of the 31 children with 2019-nCoV infection was 7 years and 1 month (6 months -17 years). Nine cases (29%) were imported cases. Other 21 cases (68%) had contact with confirmed infected adults. One case (3%) had contact with asymptomatic returnees from Wuhan. Among the 31 children, 28 patients (90%) were family cluster cases. The clinical types were asymptomatic type in 4 cases (13%), mild type in 13 cases (42%), and common type in 14 cases (45%). No severe or critical type existed. The most common symptom was fever (n=20, 65%), including 1 case of high fever, 9 cases of moderate fever, 10 cases of low fever. Fever lasted from 1 day to 9 days. The fever of fifteen cases lasted for ≤3 d, while in other 5 cases lasted > 3 d. Other symptoms included cough (n=14, 45%), fatigue (n=3, 10%) and diarrhea (n=3, 9%). Pharyngalgia, runny nose, dizziness, headache and vomiting were rare. In the early stage, the total leukocytes count in peripheral blood decreased in 2 cases (6%), the lymphocytes count decreased in 2 cases (6%), and the platelet count increased in 2 cases (6%).Elevation of C-reactive protein (10%, 3/30), erythrocyte sedimentation rate(19%,4/21), procalcitonin(4%,1/28), liver enzyme(22%, 6/27) and muscle enzyme (15%, 4/27) occurred in different proportions. Renal function and blood glucose were normal. There were abnormal chest CT changes in 14 cases, including 9 cases with patchy ground glass opacities and nodules, mostly located in the lower lobe of both lungs near the pleural area. After receiving supportive treatment, the viral nucleic acid turned negative in 25 cases within 7-23 days. Among them, 24 children (77%) recovered and were discharged from hospital. No death occurred. Conclusions: In this case series, 2019-nCoV infections in children from six provinces (autonomous region) in northern China are mainly caused by close family contact. Clinical types are asymptomatic, mild and common types. Clinical manifestations and laboratory examination results are nonspecific. Close contact history of epidemiology, nucleic acid detection and chest imaging are important bases for diagnosis. After general treatment, the short-term prognosis is good.",2020,"Wang, D.; Ju, X. L.; Xie, F.; Lu, Y.; Li, F. Y.; Huang, H. H.; Fang, X. L.; Li, Y. J.; Wang, J. Y.; Yi, B.; Yue, J. X.; Wang, J.; Wang, L. X.; Li, B.; Wang, Y.; Qiu, B. P.; Zhou, Z. Y.; Li, K. L.; Sun, J. H.; Liu, X. G.; Li, G. D.; Wang, Y. J.; Cao, A. H.; Chen, Y. N.",Zhonghua Er Ke Za Zhi,3005477624,#3049,
,CZI,Online learning-related visual impairment and preventive measures during the 2019 novel coronvirus outbreak,10.3760/cma.j.cn112142-20200219-00089,,32077665,,目前我国对2019新型冠状病毒疫情的防治工作正处于关键时期，延迟开学是减少校园内交叉感染、保护儿童和青少年身体健康、共同抗击疫情的重要举措。与此 同时，远程教学模式的大规模开展导致儿童和青少年的学习模式和用眼习惯发生巨大转变，其对儿童和青少年视觉健康的潜在影响不容忽视。本文对线上学习相关眼 健康问题和眼科疾病进行总结，并提出针对性的预防措施，为儿童和青少年在线上学习期间的视功能保护提供有效指导。（中华眼科杂志，2020，56： ）.,2020,"Lin, H. T.; Xiang, Y. F.; Cui, T. X.; Chen, J. J.",[Zhonghua yan ke za zhi] Chinese journal of ophthalmology,2123107127,#3772,
,CZI,Precautions in ophthalmic practice in the prevention and control of the novel coronavirus pneumonia epidemic,10.3760/cma.j.cn112142-20200224-00102,,32114748,,,2020,"Wang, N. L.; Jie, Y.; Tao, F. B.",Zhonghua Yan Ke Za Zhi,3004790666,#3048,
,CZI,Emergency management of prevention and control of novel coronavirus pneumonia in departments of stomatology,10.3760/cma.j.cn112144-20200205-00037,,32080994,,"Complying with overall requirements of the government and regulations on public health emergences, as well as the clinical features of diagnosis and treatment of dental illness, this paper refers to previous guidelines and studies on the infection prevention and control in dental diagnosis and treatment in China and foreign countries. Nanjing Stomatological Hospital has implemented the emergency management practices for the prevention and control of novel coronavirus pneumonia (NCP), mainly focusing on the implementation of prevention and control training programs for medical staffs and the infection control projects on the hospital environment. This study could provide reference for rapid response and emergency management for the prevention and control of NCP in the departments of stomatology.",2020,"Tang, H. S.; Yao, Z. Q.; Wang, W. M.",Zhonghua Kou Qiang Yi Xue Za Zhi,3004790666,#1930,
,CZI,Emergency management of prevention and control of novel coronavirus pneumonia in departments of stomatology,10.3760/cma.j.cn112144-20200205-00037,,,,"Complying with overall requirements of the government and regulations on public health emergences, as well as the clinical features of diagnosis and treatment of dental illness, this paper refers to previous guidelines and studies on the infection prevention and control in dental diagnosis and treatment in China and foreign countries. Nanjing Stomatological Hospital has implemented the emergency management practices for the prevention and control of novel coronavirus pneumonia (NCP), mainly focusing on the implementation of prevention and control training programs for medical staffs and the infection control projects on the hospital environment. This study could provide reference for rapid response and emergency management for the prevention and control of NCP in the departments of stomatology.",2020,"TANG, He Shu; YAO, Zhi Qing; WANG, Wen Mei",Chinese Journal of Stomatology,3004790666,#1930,
,CZI,Psychological intervention in oral patients in novel coronavirus pneumonia outbreak period,10.3760/cma.j.cn112144-20200213-00053,,32086886,,"Public health emergencies have an impact on the public mental health. The outbreak of the novel coronavirus has affected the normal diagnosis and treatment services in oral medical institutions across the country. Delay of non-emergency dental service will have a potential impact on the experience, cognition, treatment and rehabilitation of patients with oral diseases. Through literature review, this paper reviewed the oral psychosomatic diseases closely related to patients' psychological state, such as oral mucosal disease, temporomandibular joint disease, bruxism, periodontal disease and so on. It was believed that these patients might be more susceptible to the impact of stress events, and dental specialists should pay more attention to them. At the same time, this paper analyzes the possible psychological stress symptoms of patients with different oral diseases, and puts forward suggestions for remote consultation and emergency treatment of dentists. From the perspective of social role, dentists not only played the role of expert in dental home professional guidance, but also played the role of psychological counseling for patients.",2020,"Qu, X.; Zhou, X. D.",Zhonghua Kou Qiang Yi Xue Za Zhi,1991886054,#1941,
,CZI,Comparison of the clinical characteristics between RNA positive and negative patients clinically diagnosed with 2019 novel coronavirus pneumonia,10.3760/cma.j.cn112147-20200214-00095,,32087623,,"Objective: To raise awareness about 2019 novel coronavirus pneumonia (NCP) and reduce missed diagnosis rate and misdiagnosis rate by comparing the clinical characteristics between RNA positive and negative patients clinically diagnosed with NCP. Methods: From January 2020 to February 2020, 54 patients who were newly diagnosed with NCP in Wuhan Fourth Hospital were included in this study. RT-PCR method was used to measure the level of 2019-nCov RNA in pharyngeal swab samples of these patients. The patients were divided into RNA positive and negative group, and the differences of clinical, laboratory, and radiological characteristics were compared. Results: There were 31 RNA of 2019-nCov positive cases, and 23 negative cases. Common clinical symptoms of two groups were fever (80.64% vs. 86.96%) , chills (61.29% vs.52.17%) , cough (80.64% vs.95.65%) , fatigue (61.30% vs.56.52%) , chest distress (77.42% vs.73.91%) . Some other symptoms were headache, myalgia, dyspnea, diarrhea, nausea and vomiting. The laboratory and radiological characteristics of two groups mainly were lymphopenia, increased erythrocyte sedimentation rate, increased C-reactive protein, increased lactate dehydrogenase, decreased oxygenation index, normal white blood cell count and bilateral chest CT involvement. There was no statistically significant difference in other clinical characteristics except for dyspnea between two groups. Conclusions: RNA positive and negative NCP patients shared similar clinical symptoms, while RNA positive NCP patients tended to have dyspnea. Therefore, we should improve the understanding of NCP to prevent missed diagnosis and misdiagnosis; In addition, more rapid and accurate NCP diagnostic approaches should be further developed.",2020,"Li, Y. Y.; Wang, W. N.; Lei, Y.; Zhang, B.; Yang, J.; Hu, J. W.; Ren, Y. L.; Lu, Q. F.",Zhonghua Jie He He Hu Xi Za Zhi,2620894789,#1580,
,CZI,Novel coronavirus pneumonia (COVID-19) CT distribution and sign features,10.3760/cma.j.cn112147-20200217-00106,,32125131,,"Objective: To investigate the imaging findings of 2019 novel coronavirus pneumonia (COVID-19). Methods: From January 20 to February 5, 2020, a total of 130 patients diagnosed with COVID-19 from seven hospitals in China were collected. The imaging data were reviewed and analyzed in detail. Results: (1) Distribution: the lesion detected in the lung unilaterally in 14 cases (10.7%) and bilaterally in 116 cases (89.3%). According to the distribution in the lobes of the lung, all cases could be classified into subpleural distribution (102 cases, 78.4%), centrilobular distribution (99 cases, 76.1%) and diffused distribution (8 cases, 6.1%). (2) Number of lesions: single lesion 9 cases (6.9%); multiple lesions 113 cases (86.9%), diffuse lesions 8 cases (6.1%). (3) Imaging density: 70 cases (53.8%) of ground-glass opacity (GGO), 60 cases (46.2%) of GGO + consolidation. (4) Accompanying signs: 100 cases (76.9%) with vascular thickening, 98 cases (75.3%) with ""pleural parallel sign"" ; ""intralobular septal thickening"" in 100 cases (76.9%); ""halo sign"" in 13 cases (10%); ""reversed-halo sign"" in 6 cases (4.6%); pleural effusion in 3 cases (2.3 %), and pneumatocele in 2 cases (1.5%); no case with pulmonary cavity. Among 35 patients that underwent follow-up CT, 21 patients (60%) improved while 14 (40%) exacerbated. Conclusions: COVID-19 imaging characteristic mainly has subpleural, centrilobular and diffused distribution. The first two distributions can overlap or progress to diffused distribution. In the later period, it was mainly manifested as organizing pneumonia and fibrosis. The most valuable characteristic is the pleural parallel sign.",2020,"Wu, J.; Feng, C. L.; Xian, X. Y.; Qiang, J.; Zhang, J.; Mao, Q. X.; Kong, S. F.; Chen, Y. C.; Pan, J. P.",Zhonghua Jie He He Hu Xi Za Zhi,3006643024,#3276,
,CZI,Expert recommendations on the management of patients with advanced non-small cell lung cancer during epidemic of COVID-19 (Trial version),10.3760/cma.j.cn112147-20200221-00138,,32125132,,"The outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency of major international concern. Given the systemic immunosuppressive state caused by malignancy and anticancer treatments, patients with advanced lung cancer may be at a higher risk of COVID-19 infection. During epidemic of COVID-19, a guideline for the optimal management of patients with advanced lung cancer urgently needs to be proposed to distinguish the symptoms of COVID-19 and the side effects of antitumor drugs. This network questionnaire survey was conducted on the lung cancer group of the Chinese Thoracic Society, Chinese Medical Association; the lung cancer group of the Chinese Society of Clinical Oncology Youth Committee; and the Chinese Respiratory Oncology Collaboration. 321 valid questionnaires were received. Based on the guidelines on lung cancer and the results of the questionnaires, a consensus was reached. During the epidemic of COVID-19, We recommended that patients with advanced NSCLC should be treated as outpatients as possible at the nearest medical center; Patients who need to be hospitalized for antitumor treatment should be excluded from COVID-19 infection; More intensive attention should be paid to identification of COVID-19-related symptoms and adverse reactions caused by the malignancy or antitumor treatments. Stronger personal protection should be made for advanced NSCLC patients; An intentional postponing of antitumor treatment should be considered according to patient performance status. Treatment strategies should be made according to different types of advanced NSCLC patients and efficacy and toxicity of drugs.",2020,"Lung Cancer Study Group, Chinese Thoracic Society Chinese Medical Association; Chinese Respiratory Oncology, Collaboration",Zhonghua Jie He He Hu Xi Za Zhi,2059561156,#3339,
,CZI,Epidemiological characteristics of novel coronavirus pneumonia in Henan,10.3760/cma.j.cn112147-20200222-00148,,32118390,,"Objective: To study the epidemiological characteristics of COVID-19 in Henan Province. Methods: An epidemiological study was conducted based on the latest epidemic information of 1,265 confirmed cases (including regional distribution, severe illness, and deaths) announced by Health Commission of Henan Province, as well as the details of 1,079 COVID-19 officially released by Health Commission of municipalities in Henan Province collected as of 24:00 on February 19, 2020. Results: Among 1 079 patients diagnosed with COVID-19, there were 573 male (53.2%) and 505 female (46.8%) , with the ratio of male to female of 1.14:1; The majority of patients were 36-59 years old (553 cases, 51.3%) , and the mean age was 46 (interquartile range is 24) years old; 515 cases (47.7%) had a history of living, traveling, doing business in Wuhan or a brief stopover at Wuhan train stop, and 382 (35.4%) had a history of close contact with confirmed patients; There were 72 severe cases (5.7%) in 1 265 patients, and the fatality rate was 1.5%. A high number of cases were reported in Xinyang (269 cases, 21.26%) , Zhengzhou (156 cases, 12.33%) , Nanyang (155 cases, 12.25%) , Zhumadian (139 cases, 10.99%) , followed by Shangqiu (91 cases, 7.19%) , Zhoukou (76 cases, 6.01%) . Among 605 patients, the symptoms were fever (553 cases, 91.4%) , debilitation (44 cases, 7.3%) , cough (110 cases, 18.2%) , expectoration (19 cases, 3.1%) , chills (6 cases, 1.0%) , shiver (7 cases, 1.2%) , running nose (21 cases, 3.5%) , stuffy noses (8 cases, 1.3%) , throat dryness and sore (24 cases, 4.0%) , headache (21 cases, 3.5%) , chest pain (6 cases, 1.0%) , anhelation (18 cases, 3.0%) , and gastrointestinal symptom (21 cases, 3.5%) . The age of deaths ranged from 33 to 86 years old, with an average age of 72 (interquartile range of 17) years old; there be 7 males (63.6%) and 4 females (36.4%) . Conclusion: The cases in Henan Province were mainly imported cases and had certain geographical location relevance; meanwhile, there was a family-focused incidence. The overall trend of new cases was wave-like decline, and the number of deaths was high among elderly men with underlying diseases.",2020,"Cheng, J. L.; Huang, C.; Zhang, G. J.; Liu, D. W.; Li, P.; Lu, C. Y.; Li, J.",Zhonghua Jie He He Hu Xi Za Zhi,3005079553,#3067,
,CZI,The keypoints in treatment of the critical novel coronavirus pneumonia patient,10.3760/cma.j.cn112147-20200222-00151,,32087621,,"The novel coronavirus pneumonia (new coronavirus pneumonia) (NCP) has been prevalent in Wuhan and spread rapidly to all of our country. Some cases can develop into ARDS, or even death. We will share the treatment experience of severe NCP with the first-line treatment experience. The best respiratory support mode should be selected, but the timing of intubation and protection during intubation are two difficulties; patients with high level peep and poor effect in prone position can be given ECMO support. For NCP patients with mechanical ventilation, reasonable sedation and analgesia strategies should be formulated; delirium should not be ignored. In addition, there is up regulation of inflammatory factors in patients with severe NCP, but the effect of renal replacement therapy needs to be further confirmed by clinical research.",2020,"Qiu, H. B.; Li, X. Y.; Du, B.; Kang, H. Y. J.; Wang, Y. S.; Wang, F.; Sun, B.; Tong, Z. H.",Zhonghua Jie He He Hu Xi Za Zhi,3003464757,#1515,
,CZI,[Analysis of bronchoscope-guided tracheal intubation in 12 cases with COVID-19 under the personal protective equipment with positive pressure protective hood],10.3760/cma.j.cn112147-20200222-00153,,32133829,,"Endotracheal intubation is an independent risk factor for respiratory infectious diseases. We conducted a retrospective study in 12 cases with COVID-19 who underwent endotracheal intubation at ICU of the Guangzhou eighth hospital from January 20 to February 10, 2020. The intubation procedure, anesthetic regimen, and complication were collected and analyzed. The 9 healthcare workers who involved in intubation received virus nucleic acid test and 14 days temperature monitoring. All 12 patients were successfully intubated under the guidance of bronchoscope, without any complications. Midazolam, Propofol and Morphine or fentanyl were used for sedation and analgesia, avoiding patients cough and agitated during the procedure. The 9 healthcare workers were protected under the Personal Protective Equipment(PPE) with positive pressure protective hood. The detection of oropharyngeal swab virus nucleic acid were negative in all 9 healthcare workers, none of them had fever or any respiratory symptoms. The PPE with positive pressure protective hood should be needed to perform bronchoscope-guided endotracheal intubation in patients with COVID-19, it could strengthen to protect healthcare workers from virus exposure.",2020,"Cai, S. J.; Wu, L. L.; Chen, D. F.; Li, Y. X.; Liu, Y. J.; Fan, Y. Q.; Du, S. H.; Huang, H.; Liu, N.; Cheng, L. L.; Deng, X. L.; Li, S. Y.",Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases,627918116,#5083,
,CZI,[The keypoints in treatment of the critical coronavirus disease 2019 patient],10.3760/cma.j.cn112147-20200224-00159,,32111113,,"The treatment of critically ill patients with coronavirus disease 2019(COVID-19) faces compelling challenges. In this issue, we'd like to share our first-line treatment experience in treating COVID-19. Hemodynamics need be closely monitored and different types of shock should be distinguished. Vasoconstrictor drugs should be used rationally and alerting of complications is of the same importance. The risk of venous thromboembolism (VTE) needs to be assessed, and effective prevention should be carried out for high-risk patients. It is necessary to consider the possibility of pulmonary thromboembolism (PTE) in patients with sudden onset of oxygenation deterioration, respiratory distress, reduced blood pressure. However, comprehensive analysis of disease state should be taken into the interpretation of abnormally elevated D-Dimer. Nutritional support is the basis of treatment. It's important to establish individual therapy regimens and to evaluate, monitor and adjust dynamically. Under the current epidemic situation, convalescent plasma can only be used empirically, indications need to be strictly screened, the blood transfusion process should be closely monitored and the curative effect should be dynamically evaluated.",2020,"Li, X. Y.; Du, B.; Wang, Y. S.; Kang, H. Y. J.; Wang, F.; Sun, B.; Qiu, H. B.; Tong, Z. H.",Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases,2990072816,#2875,
,CZI,Expert consensus on Pulmonary Function Testing during the epidemic of Corona Virus Disease 2019,10.3760/cma.j.cn112147-20200225-00175,,32129580,,"Corona virus disease 2019 (COVID-19) is mainly transmitted by respiratory droplets and close contact. Pulmonary function testing procedures have been associated with an increasing risk of COVID-19 transmission among patients/subjects and medical staffs. Effective prevention and control strategies must be compulsorily implemented to prevent nosocomial infection. This recommendation is intended to be followed by healthcare workers (HCWs) of pulmonary function testing laboratory when COVID-19 is in epidemic. Based on the features of pulmonary function testing, precaution principles and strategies are developed in three aspects of management for HCWs, operating procedure, environment and equipment. Indications of pulmonary function testing should be followed strictly. It is strongly recommended to suspend the test for the confirmed or suspected cases of COVID-19 during the contagious stage, and to postpone the test for other patients if it is not imperative. Medical personnel should mandatorily adhere to the standard stratification of precaution measures. Patients/Subjects should be isolated in a separate area for testing. Disposable in-line filters must be used during pulmonary function testing. Cleaning and disinfection procedures for environment and equipment in pulmonary function testing laboratory should be paid more attention. 新型冠状病毒肺炎（COVID-19）主要通过呼吸道飞沫传播及密切接触传播。肺功能检查可增加医务人员和受检者发生COVID-19传播的风险，必须严 格执行有效的预防和控制措施以防止院内感染。为了指导肺功能检查室医务人员做好防控工作，本指引结合肺功能检查的特点，制订了当前疫情下肺功能检查在医务 人员管理、检查流程管理和检查环境物品管理3个方面的要求及注意事项。主要强调在疫情流行期间，必须严格掌握肺功能检查的适应证，强烈建议COVID-1 9确诊病例或疑似病例在传染期内暂缓检查，其他病患如非病情急需也暂缓检查；肺功能室医务人员应严格执行标准分级防护措施；受试者应在单独区域进行隔离检 查；检查时必须使用一次性呼吸过滤器；并重视肺功能检查环境和设备的清洁消毒。.",2020,"Task Force of Pulmonary Function, Testing; Clinical, Respiratory; Physiology, Chinese Association of Chest Physicians; Pulmonary Function Testing Group, Respiratory Therapeutics Group; Chinese Thoracic, Society",Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases,2326597313,#5440,
,CZI,"What are the highlights of ""Diagnosis and treatment of Disease 2019 novel coronavirus infection suitable for Military support Hubei medical team""",10.3760/cma.j.cn112147-20200225-00183,,32098466,,"Thousands of medical workers in the Military support Hubei medical team are exerting themselves in many hospitals in Hubei Province. They are diligent in treating patients, at the same time, they constantly summarize experience and combine the characteristics of military hospitals. According to "" the Diagnosis and Treatment of New Coronavirus Pneumonia ""(6th edition) of the National Health Commission of the People's Republic of China, a new guideline for the diagnosis and treatment of 2019 novel coronavirus infection suitable for the military (first trial version) was established. Some unique opinions and suggestions are put forward in terms of disease name, diagnosis criteria, antiviral treatment, glucocorticoid application, etc. This article will make a proper interpretation in order to understand the guideline better and help guide the diagnosis and treatment of diseases.",2020,"Shi, Y.",Zhonghua Jie He He Hu Xi Za Zhi,3005489812,#2403,
,CZI,Recommendations for respiratory rehabilitation of COVID-19 in adult,10.3760/cma.j.cn112147-20200228-00206,,32125127,,"COVID-19 is a highly infectious respiratory infection disease, which leads to dysfunction of respiratory, physical, and psychological of the patients. pulmonary rehabilitation is an important intervention for clinical patients as well as cure patients. With the deeper cognition of COVID-19 and accumulation of clinical experience, we proposed the recommendations for pulmonary rehabilitation of COVID-19 in adults based on the opinions of front-line clinical experts involved in the management of this epidemic and a review of the relevant literature and evidences: 1. for the inpatients with COVID-19, pulmonary rehabilitation would relieve the symptoms of dyspnea, anxiety, and depression; eventually improve physical function and the quality of life; 2. For severe/critical inpatients, the early performance of pulmonary rehabilitation is not suggested. 3. For isolating patients, the pulmonary rehabilitation guidence should be conducted through education video, instruction manual or remote consultation. 4. Assessment and monitor should be performed throughout the entire pulmonary rehabilitation process.5. Taking proper grading protection following the guideline. These recommendations can serve as a clinical practice guidence and basis for pulmonary rehabilitation of COVID-19.",2020,"Chinese Association of Rehabilitation, Medicine; Respiratory rehabilitation committee of Chinese Association of Rehabilitation, Medicine; Cardiopulmonary rehabilitation Group of Chinese Society of Physicai, Medicine; Rehabilitation",Zhonghua Jie He He Hu Xi Za Zhi,2354723963,#3433,
,CZI,"Cause analysis and treatment strategies of ""recurrence"" with novel coronavirus pneumonia (covid-19) patients after discharge from hospital",10.3760/cma.j.cn112147-20200229-00219,,32118391,,"With a large number of COVID-19 patients discharging from hospital, some had showed re-fever and positive nucleic acid test after discharge from hospital. This might be due to the biological characteristics of 2019-nCoV, and might also be related to the basic disease, clinical status, glucocorticoid using, sample sampling, processing and detecting of patients, and some even related to the re-infection or secondary bacterial virus infection. Therefore, we suggest that in view of this phenomenon, further stratified management of discharge from hospital should be carried out on the basis of guidelines, especially for patients with advanced age, underlying diseases or severe or critical pneumonia. For those patients who can't completely deoxygenate for a long time after hospitalization, individualized treatment methods and different discharge evaluation criteria should be adopted to ensure the complete cure of patients and prevent recurrencing after discharge from hospital. 随着新型冠状病毒肺炎（COVID-19）患者大量出院，部分患者出院后出现再次发热、核酸检测阳性的现象。这可能是由于新型冠状病毒（2019-nCo V）的生物学特性所决定的，也可能与患者的基础疾病、临床状况、糖皮质激素的使用以及标本采样、处理、检测有关，甚至还与部分患者再次感染或继发其他细菌 病毒感染有关。为此，我们建议针对这一现象，应在指南基础上进一步对患者出院进行分层管理，尤其是高龄、有基础疾病或重症及危重型患者可能要进行相应处理 措施，对于患者住院后长期吸氧难以完全脱氧者采用个体化的处理方式和不同出院评估标准，旨在保证彻底治愈患者，防止出院后""复发""。.",2020,"Zhou, L.; Liu, K.; Liu, H. G.",Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases,2041150026,#4323,
,CZI,Comparison of heart failure and 2019 novel coronavirus pneumonia in chest CT features and clinical characteristics,10.3760/cma.j.cn112148-20200218-00093,,32129583,,"Objective: To identify the characteristics including clinical features and pulmonary computed tomography (CT) features of heart failure and novel coronavirus pneumonia(COVID-19). Methods: This study was a retrospective study. A total of 7 patients with Heart failure and 12 patients with COVID-19 in the Second Xiangya Hospital of Central South University between December 1, 2019 and February 15, 2020 were enrolled. The baseline clinical and imaging features of the two groups were statistically analyzed. Results: There was no significant difference in age and sex between the two groups, but the incidence of epidemiological contact history, fever or respiratory symptoms in the COVID-19 group was significantly higher than that in the heart failure group (12/12 vs. 2/7, P=0.001; 12/12 vs. 4/7, P<0.001). While the proportion of cardiovascular diseases and impaired cardiac function was significantly less than that of the heart failure group(2/12 vs.7/7, P<0.001; 0/12 vs.7/7, P<0.001). For imaging features, both groups had ground-glass opacity and thickening of interlobular septum, but the ratio of central and gradient distribution was higher in patients with heart failure than that in patients with COVID-19 (4/7 vs. 1/12, P=0.04). In heart failure group, the ratio of the expansion of small pulmonary veins was also higher (3/7 vs. 0, P=0.013), and the lung lesions can be significantly improved after effective anti-heart failure treatment. Besides, there are more disease with rounded morphology in COVID-19 (9/12 vs. 2/7, P=0.048) . Conclusions: More patients with COVID-19 have epidemiological history and fever or respiratory symptoms. There are significant differences in chest CT features, such as enlargement of pulmonary veins, lesions distribution and morphology between heart failure and COVID-19.",2020,"Zhu, Z. W.; Tang, J. J.; Chai, X. P.; Fang, Z. F.; Liu, Q. M.; Hu, X. Q.; Xu, D. Y.; Tang, L.; Tai, S.; Wu, Y. Z.; Zhou, S. H.",Zhonghua Xin Xue Guan Bing Za Zhi,3006328792,#4358,
,CZI,Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV,10.3760/cma.j.cn112148-20200220-00105,,32120458,,"Objective: To explore the clinical characteristics and prognosis of the new coronavirus 2019-nCoV patients combined with cardiovascular disease (CVD). Methods: A retrospective analysis was performed on 112 COVID-19 patients with CVD admitted to the western district of Union Hospital in Wuhan, from January 20, 2020 to February 15, 2020. They were divided into critical group (ICU, n=16) and general group (n=96) according to the severity of the disease and patients were followed up to the clinical endpoint. The observation indicators included total blood count, C-reactive protein (CRP), arterial blood gas analysis, myocardial injury markers, coagulation function, liver and kidney function, electrolyte, procalcitonin (PCT), B-type natriuretic peptide (BNP), blood lipid, pulmonary CT and pathogen detection. Results: Compared with the general group, the lymphocyte count (0.74×10(9) (0.34×10(9), 0.94×10(9))/L vs. 0.99×10(9) (0.71×10(9), 1.29×10(9))/L, P=0.03) was extremely lower in the critical group, CRP (106.98 (81.57, 135.76) mg/L vs. 34.34 (9.55,76.54) mg/L, P<0.001) and PCT (0.20 (0.15,0.48) μg/L vs. 0.11 (0.06,0.20)μg/L, P<0.001) were significantly higher in the critical group. The BMI of the critical group was significantly higher than that of the general group (25.5 (23.0, 27.5) kg/m(2) vs. 22.0 (20.0, 24.0) kg/m(2), P=0.003). Patients were further divided into non-survivor group (17, 15.18%) group and survivor group (95, 84.82%). Among the non-survivors, there were 88.24% (15/17) patients with BMI> 25 kg/m(2), which was significantly higher than that of survivors (18.95% (18/95), P<0.001). Compared with the survived patients, oxygenation index (130 (102, 415) vs. 434 (410, 444), P<0.001) was significantly lower and lactic acid (1.70 (1.30, 3.00) mmol/L vs. 1.20 (1.10, 1.60) mmol/L, P<0.001) was significantly higher in the non-survivors. There was no significant difference in the proportion of ACEI/ARB medication between the critical group and the general group or between non-survivors and survivors (all P>0.05). Conclusion: COVID-19 patients combined with CVD are associated with a higher risk of mortality. Critical patients are characterized with lower lymphocyte counts. Higher BMI are more often seen in critical patients and non-survivor. ACEI/ARB use does not affect the morbidity and mortality of COVID-19 combined with CVD. Aggravating causes of death include fulminant inflammation, lactic acid accumulation and thrombotic events.",2020,"Peng, Y. D.; Meng, K.; Guan, H. Q.; Leng, L.; Zhu, R. R.; Wang, B. Y.; He, M. A.; Cheng, L. X.; Huang, K.; Zeng, Q. T.",Zhonghua Xin Xue Guan Bing Za Zhi,2965860541,#3321,
,CZI,[Analysis of myocardial injury in patients with COVID-19 and association between concomitant cardiovascular diseases and severity of COVID-19],10.3760/cma.j.cn112148-20200225-00123,,32141280,,"Objective: To evaluate the cardiovascular damage of patients with COVID-19, and determine the correlation of serum N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin-I (cTnI) with the severity of COVID-19, and the impact of concomitant cardiovascular disease on severity of COVID-19 was also evaluated. Methods: A cross-sectional study was designed on 150 consecutive patients with COVID-19 in the fever clinic of Tongji Hospital in Wuhan from January to February in 2020, including 126 mild cases and 24 cases in critical care. Both univariate and multivariate logistic regression were used to analyze the correlation of past medical history including hypertension, diabetes and coronary heart disease (CHD) , as well as the levels of serum NT-proBNP and cTnI to the disease severity of COVID-19 patients. Results: Age, hypersensitive C-reactive protein(hs-CRP) and serum creatinine levels of the patients were higher in critical care cases than in mild cases(all P<0.05). Prevalence of male, elevated NT-proBNP and cTnI, hypertension and coronary heart disease were significantly higher in critical cases care patients than in the mild cases(all P<0.05). Univariate logistic regression analysis showed that age, male, elevated NT-proBNP, elevated cTnI, elevated hs-CRP, elevated serum creatinine, hypertension, and CHD were significantly correlated with critical disease status(all P<0.05). Multivariate logistic regression analysis showed that elevated cTnI(OR=26.909, 95%CI 4.086-177.226, P=0.001) and CHD (OR=16.609, 95%CI 2.288-120.577, P=0.005) were the independent risk factors of critical disease status. Conclusions: COVID-19 can significantly affect the heart function and lead to myocardial injury. The past medical history of CHD and increased level of cTnI are two independent determinants of clinical disease status in patients with COVID-19.",2020,"Chen, C.; Yan, J. T.; Zhou, N.; Zhao, J. P.; Wang, D. W.",Zhonghua xin xue guan bing za zhi,2913916509,#5104,
,CZI,Health protection guideline of mobile cabin hospitals during Novel Coronavirus Pneumonia (NPC) outbreak,10.3760/cma.j.cn112150-20200217-00121,,32072919,,"This guideline is applicable to the health protection requirements of large indoor stadiums which are reconstructed as treatment sites for the Novel Coronavirus Pneumonia (NPC) patients with mild symptoms during the outbreak. Focusing on the health emergency scenario of severe virus infectious diseases and atypical places where NPC patients with mild symptom gather, from perspectives of functional zones, hygiene facilities, personal protection, and management system, health risk protection recommendations and countermeasures are comprehensively proposed to mainly protect staffs and surrounding environment. The implementation of this guideline will provide technique support for emergency requirements of indoor stadiums reconstructed as mobile cabin hospitals.",2020,"Novel Coronavirus Pneumonia Emergency Response Key Places, Protection; Disinfection Technology Team, Chinese Center for Disease Control; Prevention",Zhonghua Yu Fang Yi Xue Za Zhi,1992330641,#1277,
,CZI,Health protection guideline of passenger transport stations and transportation facilities during novel coronavirus pneumonia (NCP) outbreak,10.3760/cma.j.cn112150-20200217-00130,,32072920,,"During the coronavirus pneumonia (NCP) outbreak, the transportation industries are faced with the more burdensome tasks of outbreak prevention and control as well as ensuring smooth transportation. It is important to organize transportation in order to restore the order of production and life, ensure the normal economic and social operation, and control the outbreak in the whole society. From the perspective of health, this guideline puts forward technical requirements on the operation management, personnel requirements and health protection of passenger transportation places such as aviation, railway, subway, bus, taxi, ship, etc., which reduces the impact of the NCP outbreak on the transportation industry and personal health risks.",2020,"Novel Coronavirus Pneumonia Emergency Response Key Places, Protection; Disinfection Technology Team, Chinese Center for Disease Control; Prevention",Zhonghua Yu Fang Yi Xue Za Zhi,2509882129,#1278,
,CZI,Technologies and requirements of protection and disinfection in key places during the novel coronavirus pneumonia (NCP) outbreak,10.3760/cma.j.cn112150-20200217-00131,,32077664,,"Novel coronavirus pneumonia (NCP), a new respiratory infectious disease, has become an important public health problem. Inappropriate protection and disinfection measures are potential risk factors of transmission and outbreak of NCP in key places. This theme issue is concerned with the prevention and control of NCP. Comprehensive measures and suggestions for protection and disinfection are put forward from perspectives of functional areas in key places, such as hotels, mobile cabin hospitals, passenger transport stations and public transport facilities, environment and facilities, personal protection, operation management system, etc., so as to provide technical support for the prevention and control of new respiratory infectious diseases.",2020,"Novel Coronavirus Pneumonia Emergency Response Key Places, Protection; Disinfection Technology Team, Chinese Center for Disease Control; Prevention",Zhonghua Yu Fang Yi Xue Za Zhi,2166798197,#1537,
,CZI,Risk assessment of exported risk of novel coronavirus pneumonia from Hubei Province,10.3760/cma.j.cn112150-20200219-00142,,32083409,,"Objective: To evaluate the exported risk of novel coronavirus pneumonia (NCP) from Hubei Province and the imported risk in various provinces across China. Methods: Data of reported NCP cases and Baidu Migration Indexin all provinces of the country as of February 14, 2020 were collected. The correlation analysis between cumulative number of reported cases and the migration index from Hubei was performed, and the imported risks from Hubei to different provinces across China were further evaluated. Results: A total of 49 970 confirmed cases were reported nationwide, of which 37 884 were in Hubei Province. The average daily migration index from Hubei to other provinces was 312.09, Wuhan and other cities in Hubei were 117.95 and 194.16, respectively. The cumulative NCP cases of provinces was positively correlated with the migration index derived from Hubei province, also in Wuhan and other cities in Hubei, with correlation coefficients of 0.84, 0.84, and 0.81. In linear model, population migration from Hubei Province, Wuhan and other cities in Hubei account for 71.2%, 70.1%, and 66.3% of the variation, respectively. The period of high exported risk from Hubei occurred before January 27, of which the risks before January 23 mainly came from Wuhan, and then mainly from other cities in Hubei. Hunan Province, Henan Province and Guangdong Province ranked the top three in terms of cumulative imported risk (the cumulative risk indices were 58.61, 54.75 and 49.62 respectively). Conclusion: The epidemic in each province was mainly caused by the importation of Hubei Province. Taking measures such as restricting the migration of population in Hubei Province and strengthening quarantine measures for immigrants from Hubei Province may greatly reduce the risk of continued spread of the epidemic.",2020,"Hu, J. X.; He, G. H.; Liu, T.; Xiao, J. P.; Rong, Z. H.; Guo, L. C.; Zeng, W. L.; Zhu, Z. H.; Gong, D. X.; Yin, L. H.; Wan, D. H.; Zeng, L. L.; Ma, W. J.",Zhonghua Yu Fang Yi Xue Za Zhi,3003596834,#1627,
,CZI,[The importance of strengthening the ability of fundamental disease prevention and control system from the perspective of the epidemic situation of COVID-19],10.3760/cma.j.cn112150-20200220-00149,,32107911,,"COVID-19 has been in epidemic for nearly two months. The prevention and control measures have achieved remarkable results. From the response and disposal process of this epidemic, it is exposed that fundamental disease prevention and control system are insufficient in human resources and ability of laboratory testing. It is suggested that the disease control institutions should strengthen the construction of these aspects in future.",2020,"Wang, M.",Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine],2366762302,#2968,
,CZI,[Analysis on epidemic situation and spatiotemporal changes of COVID-19 in Anhui],10.3760/cma.j.cn112150-20200221-00150,,32107910,,"We used the epidemic data of COVID-19 published on the official website of the municipal health commission in Anhui province. We mapped the spatiotemporal changes of confirmed cases, fitted the epidemic situation by the population growth curve at different stages and took statistical description and analysis of the epidemic situation in Anhui province. It was found that the cumulative incidence of COVID-19 was 156/100 000 by February 18, 2020 and the trend of COVID-19 epidemic declined after February 7, changing from J curve to S curve. The actual number of new cases began to decrease from February 2 to February 4 due to the time of case report and actual onset delayed by 3 to 5 days.",2020,"Liu, M.; Xu, H. L.; Yuan, M.; Liu, Z. R.; Wu, X. Y.; Zhang, Y.; Ma, L. Y.; Gong, L.; Gan, H.; Zong, W. W.; Tao, S. M.; Liu, Q.; Du, Y. N.; Tao, F. B.",Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine],3006643024,#2886,
,CZI,Thoughts and suggestions on modern construction of disease prevention and control system,10.3760/cma.j.cn112150-20200221-00151,,32100978,,"The critical period for the prevention and control of novel coronavirus pneumonia (NCP) in China, in response to requirements for accelerating the modernization of the disease prevention and control system, we analyzed and summarized the current situation, existing problems, and deficiencies in China's modernization of disease prevention and control system. In addition, we put forward the contents and countermeasures for the modernization of the disease prevention and control system. The modernization of the disease prevention and control system should be built around governance modernization, talent modernization, equipment modernization, scientific research modernization, and modernization of the regulatory system. The countermeasures and suggestions need to reposition the disease prevention and control system, rationalize the management system and operating mechanism, strengthen the modernization of talents and equipment, strengthen scientific research on disease prevention and control, and further improve the disease prevention and control legal system.",2020,"Cheng, J. Q.",Zhonghua Yu Fang Yi Xue Za Zhi,2387214729,#2327,
,CZI,Epidemic trend of corona virus disease 2019 (COVID-19) in mainland China,10.3760/cma.j.cn112150-20200222-00163,,32125133,,"Objective: In order to master the epidemic trend of corona virus disease 2019 (COVID-19) and evaluate the effect of prevention and control, we evaluate the epidemic dynamics of COVID-19 in mainland China, Hubei province, Wuhan city and other provinces outside Hubei from January 16 to February 14, 2020. Methods: We collected the daily number of new confirmed COVID-19 cases by nucleic acid detection reported by the National Health Commission from January 16, 2020 to February 14, 2020. The analysis includes the epidemic curve of the new confirmed cases, multiple of the new confirmed cases for period-over-period, multiple of the new confirmed cases for fixed-base, and the period-over-period growth rate of the new confirmed cases. Results: From January 16 to February 14, 2020, the cumulative number of new confirmed cases of COVID-19 in mainland China was 50 031, including 37 930 in Hubei province, 22 883 in Wuhan city and 12 101 in other provinces outside Hubei. The peak of the number of new confirmed cases in other provinces outside Hubei was from January 31 to February 4, 2020, and the peak of new confirmed cases in Wuhan city and Hubei province was from February 5 to February 9, 2020. The number of new confirmed cases in other provinces outside Hubei showed a significant decline (23% compared with the peak) from February 5 to February 9, 2020, while the number of new confirmed cases in Wuhan city (30% compared with the peak) and Hubei Province (37% compared with the peak) decreased significantly from February 10 to February 14, 2020. Conclusion: The epidemic prevention and control measures taken by the state and governments at all levels have shown very significant effects, effectively curbing the spread of the COVID-19 epidemic in China.",2020,"Zhu, Z. B.; Zhong, C. K.; Zhang, K. X.; Dong, C.; Peng, H.; Xu, T.; Wang, A. L.; Guo, Z. R.; Zhang, Y. H.",Zhonghua Yu Fang Yi Xue Za Zhi,3006645647,#3231,
,CZI,Analysis on the epidemic factors for the Corona Virus Disease,10.3760/cma.j.cn112150-20200227-00196,,32125129,,"Since December 2019, corona virus disease 2019 (COVID-19) , an emerging infection disease occurred in Wuhan, has spread in the mainland China. The epidemic factors on the basis of knowledge of SARS-CoV-2 were discussed in this paper. This puts a lot of pressure on clinical resources and care. SARS-CoV-2 is a novel corona virus, the onset of COVID-19 is slow, and the pathogenesis of SARS-CoV-2 remains unclear and may lead to multiple organ damage. These put a lot of pressure on clinical resources and care. Source of infection including the patients, asymptomatic carrier and patients in the incubation period are contagious. It is difficult to control source of infection. Routes of SARS-CoV-2 transmission are diversified and the main routes of transmission for COVID-19 are droplet transmission and close contact transmission. All population have susceptibility to SARS-CoV-2. Social factors such population movements and aggregation accelerated the spread of SARS-CoV-2. The Chinese government's adopted measures are positive and effective, and are accepted by the expert group from the World Health Organization. However, it will be a long-term hard work in the future to seriously summarize and think deeply to achieve public health security in China.",2020,"Yang, H. Y.; Duan, G. C.",Zhonghua Yu Fang Yi Xue Za Zhi,2002726211,#3262,
,CZI,Pregnant women with new coronavirus infection: a clinical characteristics and placental pathological analysis of three cases,10.3760/cma.j.cn112151-20200225-00138,,32114744,,"Objective: To investigate the clinical characteristics and placental pathology of 2019-nCoV infection in pregnancy, and to evaluate intrauterine vertical transmission potential of 2019-nCoV infection. Methods: The placentas delivered from pregnant women with confirmed 2019-nCoV infection which were received in the Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology collected by February 4th, 2020 and retrospectively studied. Their clinical material including placental tissue and lung CT, and laboratory results were collected, meanwhile, nucleic acid detection of 2019-nCoV of the placentas were performed by RT-PCR. Results: Three placentas delivered from pregnant women with confirmed 2019-nCoV infection, who were all in their third trimester with emergency caesarean section. All of the three patients presented with fever (one before caesarean and two in postpartum), and had no significant leukopenia and lymphopenia. Neonatal throat swabs from three newborns were tested for 2019-nCoV, and all samples were negative for the nucleic acid of 2019-nCoV. One premature infant was transferred to Department of Neonatology due to low birth weight. By the end of February 25, 2020, none of the three patients developed severe 2019-nCoV pneumonia or died(two patients had been cured and discharged, while another one had been transferred to a square cabin hospital for isolation treatment). There were various degrees of fibrin deposition inside and around the villi with local syncytial nodule increases in all three placentas. One case of placenta showed the concomitant morphology of chorionic hemangioma and another one with massive placental infarction. No pathological change of villitis and chorioamnionitis was observed in our observation of three cases. All samples from three placentas were negative for the nucleic acid of 2019-nCoV. Conclusions: The clinical characteristics of pregnant women with 2019-nCoV infection in late pregnancy are similar to those of non-pregnant patients, and no severe adverse pregnancy outcome is found in the 3 cases of our observation. Pathological study suggests that there are no morphological changes related to infection in the three placentas. Currently no evidence for intrauterine vertical transmission of 2019-nCoV is found in the three women infected by 2019-nCoV in their late pregnancy.",2020,"Chen, S.; Huang, B.; Luo, D. J.; Li, X.; Yang, F.; Zhao, Y.; Nie, X.; Huang, B. X.",Zhonghua Bing Li Xue Za Zhi,3005679569,#3068,
,CZI,Detection of 2019-nCoV in the pathological paraffin embedded tissue,10.3760/cma.j.cn112151.20200219.00001,,32084674,,,2020,"Xu, S. P.; Kuang, D.; Hu, Y.; Liu, C.; Duan, Y. Q.; Wang, G. P.",Zhonghua Bing Li Xue Za Zhi,1757240742,#1448,
,CZI,Health management of breast cancer patients outside the hospital during the outbreak of 2019 novel coronavirus disease,10.3760/cma.j.cn112152-20200221-00110,,32100979,,"The outbreak of 2019 novel coronavirus disease (COVID-19) is spreading rapidly. In order to prevent cluster outbreaks, the government strengthened the management and control of personnel mobility, which had a great impact on the examination and treatment of breast cancer patients. This paper discusses how to realize scientific health management of breast cancer patients outside the hospital based on the existing epidemic situation, characteristics of breast cancer patients and public health safety factors. The breast cancer patients should synthetically consider the epidemic prevention situation of inhabitance, the disease stage and previous therapeutic schedule to decide the next therapeutic schedule. If necessary, after professional discussion and communication between doctors and patients online or offline, the hospital visiting time should be delayed through seeking alternative treatment schemes, and psychological counseling for patients should be paid attention to at the same time.",2020,"Liu, B. L.; Ma, F.; Wang, J. N.; Fan, Y.; Mo, H. N.; Xu, B. H.",Zhonghua Zhong Liu Za Zhi,2535587098,#2191,
,CZI,Surgical treatment strategy for digestive system malignancies during the outbreak of novel coronavirus pneumonia,10.3760/cma.j.cn112152-20200223-00117,,32096396,,"The outbreak of novel coronavirus pneumonia occurred in Wuhan, Hubei province of China, at the end of 2019, and spread rapidly across the country. After the outbreak of this disease, the overwhelming majority of cities have launched the ""first level response"" and the regular diagnosis and treatment of cancer patients are greatly affected. The digestive systemic cancer is the most common malignancy. Most patients are diagnosed in the advanced stage with poor prognosis. The epidemic of novel coronavirus pneumonia poses new challenges to diagnosis and treatment of the patients with digestive system malignancies. Based on the fully understanding of the characteristics of digestive system tumors, we should change the treatment strategy and adopt more reasonable treatment strategy timely during the epidemic period to minimize the adverse effects of the epidemic of novel coronavirus pneumonia on the treatment.",2020,"Ma, F. H.; Hu, H. T.; Tian, Y. T.",Zhonghua Zhong Liu Za Zhi,2366820445,#2176,
,CZI,[Surgical treatment for esophageal cancer during the outbreak of COVID-19],10.3760/cma.j.cn112152-20200226-00128,,32105052,,"Since December 2019, unexplained pneumonia has appeared in Wuhan City, Hubei Province, and a new type of coronavirus infection was confirmed as COVID-19. COVID-19 spread rapidly nationwide and abroad. The COVID-19 has brought huge impacts to all the people and walks of life, especially to the medical and health systems. It has also brought great challenges to the treatment of patients with cancer. Esophageal cancer is a common malignant tumor in China and most of the patients are in the middle and advanced stage when diagnosed, with immunosuppressive and poor prognosis. The selection of surgical procedures and perioperative managements of esophageal cancer require all thoracic surgeons work together to figure out a reasonable system of surgical treatment and emergency response.",2020,"Li, Y.; Qin, J. J.; Wang, Z.; Yu, Y.; Wen, Y. Y.; Chen, X. K.; Liu, W. X.",Zhonghua zhong liu za zhi [Chinese journal of oncology],1972328982,#2876,
,CZI,[Discussion on diagnosis and treatment of hepatobiliary malignancies during the outbreak of novel coronavirus pneumonia],10.3760/cma.j.cn112152-20200227-00137,,32108460,,"From December 2019, the new coronavirus pneumonia (COVID-19) broke out in Wuhan, Hubei, and spread rapidly to the nationwide. On January 20, 2020, the National Health Committee classified COVID-19 pneumonia as one of B class infectious diseases and treated it as class A infectious disease. During the epidemic period, the routine diagnosis and treatment of tumor patients was affected with varying degrees. In this special period, we performed the superiority of the multi-disciplinary team of diagnosis and treatment, achieved accurate diagnosis and treatment of patients with hepatobiliary malignant tumors, provided support for these patients with limited medical resources, and helped them to survive during the epidemic period.On the basis of fully understanding the new coronavirus pneumonia, the treatment strategy should be changed timely during the epidemic, and more appropriate treatment methods should be adopted to minimize the adverse effect of the epidemic on tumor treatment.",2020,"Wu, F.; Song, Y.; Zeng, H. Y.; Ye, F.; Rong, W. Q.; Wang, L. M.; Wu, J. X.",Zhonghua zhong liu za zhi [Chinese journal of oncology],3003637715,#2977,
,CZI,[Medical diagnosis and treatment strategies for malignant tumors of the digestive system during the outbreak of novel coronavirus pneumonia],10.3760/cma.j.cn112152-20200227-00141,,32112549,,"Since the outbreak of novel coronavirus pneumonia in December 2019, the diagnosis and treatment of patients with cancer have been facing great challenges. Although oncologists are not fighting on the front line to against the epidemic, during this special period, we should not only protect patients, their families and medical staff from the infection of novel Coronavirus, but also minimize the impact of the epidemic on the diagnosis and the treatment of patients with cancer. Combining the guidelines for diagnosis and treatment of tumors with our clinical experience, in this epidemic period, we discuss the strategies for diagnosis, treatment, and follow-up of malignant tumors of the digestive system in this article.",2020,"Zhang, Y.; Xu, J. M.",Zhonghua zhong liu za zhi [Chinese journal of oncology],1681405782,#3026,
,CZI,Individualized treatment recommendations for lung cancer patients at different stages of treatment during the outbreak of 2019 novel coronavirus disease epidemic,10.3760/cma.j.cn112152-20200228-00146,,32125130,,"In order to achieve the overall victory of the 2019 novel coronavirus disease epidemic in this 'war', especially to prevent the disease recurrence from rebounding during the resumption of labor, the government has not loosened any control of personnel mobility, which has obviously affected the normal examination and treatment of lung cancer patients under the influence of this epidemic. During the epidemic period, cancer patients with low immunity levels face the double ordeals of disease and epidemic situation. Compared with the general population, they are more likely to be infected with the new coronavirus. Among the infected cancer patients, lung cancer is the most common type. It is necessary to provide more appropriate individualized treatment recommendations for patients with lung cancer based on the epidemic situation of the patient's location and in combination with the patient's own condition. Through active prevention of infection, timely conversion of treatment strategies, online and offline joint control, and positive psychological counseling, we significantly hope to help patients with lung cancer to survive this difficult period.",2020,"Zhao, Z.; Bai, H.; Duan, J. C.; Wang, J.",Zhonghua Zhong Liu Za Zhi,58565763,#3237,
,CZI,Diagnostic and therapeutic strategies of lung cancer patients during the outbreak of 2019 novel coronavirus disease (COVID-19),10.3760/cma.j.cn112152-20200229-00152,,32118394,,"With the increasing number of cases and widening geographical spread, the 2019 novel coronavirus disease (COVID-19) has been classified as one of the class B infectious diseases but prevented and controlled as class A infectious disease by the National Health Commission of China. The diagnosis and treatment of lung cancer patients have been challenged greatly because of extraordinary public health measures since the lung cancer patients are a high-risk population during the COVID-19 outbreak period. Strict protection for lung cancer patients is needed to avoid infection. Lung cancer patients are difficult to differentiate from patients with COVID-19 in terms of clinical symptoms, which will bring great trouble to the clinical work and physical and mental health of lung cancer patients. This review will demonstrate how to applicate appropriate and individual management for lung cancer patients to protect them from COVID-19.",2020,"Yang, L.; Xu, H. Y.; Wang, Y.",Zhonghua Zhong Liu Za Zhi,2763173940,#3045,
,CZI,[The differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of the 2019 novel coronavirus disease],10.3760/cma.j.cn112152-20200303-00166,,32133833,,"Objective: To investigate the principles of differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of novel coronavirus (2019-nCoV) by analyzing one case of lymphoma who presented pulmonary ground-glass opacities (GGO) after courses of chemotherapy. Methods: Baseline demographics and clinicopathological data of eligible patients were retrieved from medical records. Information of clinical manifestations, history of epidemiology, lab tests and chest CT scan images of visiting patients from February 13 to February 28 were collected. Literatures about pulmonary infiltrates in cancer patients were searched from databases including PUBMED, EMBASE and CNKI. Results: Among the 139 cancer patients underwent chest CT scans before chemotherapy, pulmonary infiltrates were identified in eight patients (5.8%), five of whom were characterized as GGOs in lungs. 2019-nCoV nuclear acid testing was performed in three patients and the results were negative. One case was a 66-year-old man diagnosed as non-Hodgkin lymphoma and underwent CHOP chemotherapy regimen. His chest CT scan image displayed multiple GGOs in lungs and the complete blood count showed decreased lymphocytes. This patient denied any contact with confirmed/suspected cases of 2019-nCoV infection and without fever and other respiratory symptoms. Considering the negative result of nuclear acid testing, this patient was presumptively diagnosed as viral pneumonia and an experiential anti-infection treatment had been prescribed for him. Conclusions: The 2019 novel coronavirus disease (COVID-19) complicates the clinical scenario of pulmonary infiltrates in cancer patients. The epidemic history, clinical manifestation, CT scan image and lab test should be combined consideration. The 2019-nCoV nuclear acid testing might be applicated in more selected patients. Active anti-infection treatment and surveillance of patient condition should be initiated if infectious disease is considered.",2020,"Zhu, W. J.; Wang, J.; He, X. H.; Qin, Y.; Yang, S.; Hu, X. S.; Wang, H. Y.; Huang, J.; Zhou, A. P.; Ma, F.; Shi, Y. K.; Zhou, S. Y.",Zhonghua zhong liu za zhi [Chinese journal of oncology],2604139211,#5530,
,CZI,Study on assessing early epidemiological parameters of coronavirus disease epidemic in China,10.3760/cma.j.cn112338-20200205-00069,,32113196,,"Objective: To study the early dynamics of the epidemic of coronavirus disease (COVID-19) in China from 15 to 31 January, 2020, and estimate the corresponding epidemiological parameters (incubation period, generation interval and basic reproduction number) of the epidemic. Methods: By means of Weibull, Gamma and Lognormal distributions methods, we estimated the probability distribution of the incubation period and generation interval data obtained from the reported COVID-19 cases. Moreover, the AIC criterion was used to determine the optimal distribution. Considering the epidemic is ongoing, the exponential growth model was used to fit the incidence data of COVID-19 from 10 to 31 January, 2020, and exponential growth method, maximum likelihood method and SEIR model were used to estimate the basic reproduction number. Results: Early COVID-19 cases kept an increase in exponential growth manner before 26 January, 2020, then the increase trend became slower. The average incubation period was 5.01 (95%CI: 4.31-5.69) days; the average generation interval was 6.03 (95%CI: 5.20-6.91) days. The basic reproduction number was estimated to be 3.74 (95%CI: 3.63-3.87), 3.16 (95%CI: 2.90-3.43), and 3.91 (95%CI: 3.71-4.11) by three methods, respectively. Conclusions: The Gamma distribution fits both the generation interval and incubation period best, and the mean value of generation interval is 1.02 day longer than that of incubation period. The relatively high basic reproduction number indicates that the epidemic is still serious; Based on our analysis, the turning point of the epidemic would be seen on 26 January, the growth rate would be lower afterwards.",2020,"Song, Q. Q.; Zhao, H.; Fang, L. Q.; Liu, W.; Zheng, C.; Zhang, Y.",Zhonghua Liu Xing Bing Xue Za Zhi,3002764620,#3053,
,CZI,Dynamic basic reproduction number based evaluation for current prevention and control of COVID-19 outbreak in China,10.3760/cma.j.cn112338-20200209-00080,,32113197,,"Objective: To evaluate the current status of the prevention and control of coronavirus disease (COVID-19) outbreak in China, establish a predictive model to evaluate the effects of the current prevention and control strategies, and provide scientific information for decision- making departments. Methods: Based on the epidemic data of COVID-19 openly accessed from national health authorities, we estimated the dynamic basic reproduction number R(0)(t) to evaluate the effects of the current COVID-19 prevention and control strategies in all the provinces (municipalities and autonomous regions) as well as in Wuhan and the changes in infectivity of COVID-19 over time. Results: For the stability of the results, 24 provinces (municipality) with more than 100 confirmed COVID-19 cases were included in the analysis. At the beginning of the outbreak, the R(0)(t) showed unstable trend with big variances. As the strengthening of the prevention and control strategies, R(0)(t) began to show a downward trend in late January, and became stable in February. By the time of data analysis, 18 provinces (municipality) (75%) had the R(0)(t)s less than 1. The results could be used for the decision making to free population floating conditionally. Conclusions: Dynamic R(0)(t) is useful in the evaluation of the change in infectivity of COVID-19, the prevention and control strategies for the COVID-19 outbreak have shown preliminary effects, if continues, it is expected to control the COVID-19 outbreak in China in near future.",2020,"Huang, L. L.; Shen, S. P.; Yu, P.; Wei, Y. Y.",Zhonghua Liu Xing Bing Xue Za Zhi,1967501958,#3063,
,CZI,"Estimating the basic reproduction number of COVID-19 in Wuhan, China",10.3760/cma.j.cn112338-20200210-00086,,32125128,,"Objective: The number of confirmed and suspected cases of the COVID-19 in Hubei province is still increasing. However, the estimations of the basic reproduction number of COVID-19 varied greatly across studies. The objectives of this study are 1) to estimate the basic reproduction number (R(0)) of COVID-19 reflecting the infectiousness of the virus and 2) to assess the effectiveness of a range of controlling intervention. Method: The reported number of daily confirmed cases from January 17 to February 8, 2020 in Hubei province were collected and used for model fit. Four methods, the exponential growth (EG), maximum likelihood estimation (ML), sequential Bayesian method (SB) and time dependent reproduction numbers (TD), were applied to estimate the R(0). Result: Among the four methods, the EG method fitted the data best. The estimated R(0) was 3.49 (95% CI: 3.42-3.58) by using EG method. The R(0) was estimated to be 2.95 (95%CI: 2.86-3.03) after taking control measures. Conclusion: In the early stage of the epidemic, it is appropriate to estimate R(0) using the EG method. Meanwhile, timely and effective control measures were warranted to further reduce the spread of COVID-19.",2020,"Wang, Y.; You, X. Y.; Wang, Y. J.; Peng, L. P.; Du, Z. C.; Gilmour, S.; Yoneoka, D.; Gu, J.; Hao, C.; Hao, Y. T.; Li, J. H.",Zhonghua Liu Xing Bing Xue Za Zhi,3006535772,#3278,
,CZI,Prediction modeling with data fusion and prevention strategy analysis for the COVID-19 outbreak,10.3760/cma.j.cn112338-20200216-00107,,32129581,,"Since December 2019, the outbreak of COVID-19 in Wuhan has spread rapidly due to population movement during the Spring Festival holidays. Since January 23rd, 2020, the strategies of containment and contact tracing followed by quarantine and isolation has been implemented extensively in mainland China, and the rates of detection and confirmation have been continuously increased, which have effectively suppressed the rapid spread of the epidemic. In the early stage of the outbreak of COVID-19, it is of great practical significance to analyze the transmission risk of the epidemic and evaluate the effectiveness and timeliness of prevention and control strategies by using mathematical models and combining with a small amount of real-time updated multi-source data. On the basis of our previous research, we systematically introduce how to establish the transmission dynamic models in line with current Chinese prevention and control strategies step by step, according to the different epidemic stages and the improvement of the data. By summarized our modelling and assessing ideas, the model formulations vary from autonomous to non-autonomous dynamic systems, the risk assessment index changes from the basic regeneration number to the effective regeneration number, and the epidemic development and assessment evolve from the early SEIHR transmission model-based dynamics to the recent dynamics which are mainly associated with the variation of the isolated and suspected population sizes.",2020,"Tang, S. Y.; Xiao, Y. N.; Peng, Z. H.; Shen, H. B.",Zhonghua Liu Xing Bing Xue Za Zhi,1952209694,#4357,
,CZI,[Investigation and analysis on characteristics of a cluster of COVID-19 associated with exposure in a department store in Tianjin],10.3760/cma.j.cn112338-20200221-00139,,32133830,,"Objective: To describe the epidemiological characteristics of a cluster of COVID-19 cases reported in Baodi district of Tianjin as of 18 February, 2020, which might be associated with the exposure in a local department store, and provide suggestions for prevention and control strategy development. Methods: The basic characteristics, time and area distributions, clinical manifestations, epidemiological history and transmission mode of the COVID-19 cases associated with the department store exposure were analyzed. Results: A total of 40 COVID-19 cases were associated with the department store exposure, accounting for 75.47% of the total confirmed cases (53 cases) reported in Baodi district. The cases were mainly at the age of 60 years or older (35.00%) and farmers (40.00%). The main clinical manifestations included fever (95.00%), cough (35.00%), and diarrhea (15.00%). The proportion of confirmed severe cases was 32.50%. The incidence curve showed that the incidence peak occurred on 31 January, 2020. Among the 40 cases, 6(15.00%) were department store employees, 19(47.50%) were customers and 15(37.50%) were close contacts (secondary cases). The first case occurred on 21 January, 2020, this case was a department store employee who had a purchasing history at whole sale markets in other provinces and cities before the onset, and 3 employees were still on duty after symptom onsets. The median of the incubation period of customer cases was 6 days, and the median of the interval between onset and medical treatment of customer cases was 7 days. Conclusion: This was a cluster epidemic of COVID-19, which might be associated with the exposure in the department store. By now, the current prevention and control measures have achieved satisfied effects.",2020,"Wu, W. S.; Li, Y. G.; Wei, Z. F.; Zhou, P. H.; Lyu, L. K.; Zhang, G. P.; Zhao, Y.; He, H. Y.; Li, X. Y.; Gao, L.; Zhang, X. M.; Liu, H.; Zhou, N.; Guo, Y.; Zhang, D.; Liu, J.; Zhang, Y.",Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi,1608673380,#5319,
,CZI,[Potential false-positive rate among the 'asymptomatic infected individuals' in close contacts of COVID-19 patients],10.3760/cma.j.cn112338-20200221-00144,,32133832,,"Objective: As the prevention and control of COVID-19continues to advance, the active nucleic acid test screening in the close contacts of the patients has been carrying out in many parts of China. However, the false-positive rate of positive results in the screening has not been reported up to now. But to clearify the false-positive rate during screening is important in COVID-19 control and prevention. Methods: Point values and reasonable ranges of the indicators which impact the false-positive rate of positive results were estimated based on the information available to us at present. The false-positive rate of positive results in the active screening was deduced, and univariate and multivariate-probabilistic sensitivity analyses were performed to understand the robustness of the findings. Results: When the infection rate of the close contacts and the sensitivity and specificity of reported results were taken as the point estimates, the positive predictive value of the active screening was only 19.67%, in contrast, the false-positive rate of positive results was 80.33%. The multivariate-probabilistic sensitivity analysis results supported the base-case findings, with a 75% probability for the false-positive rate of positive results over 47%. Conclusions: In the close contacts of COVID-19 patients, nearly half or even more of the 'asymptomatic infected individuals' reported in the active nucleic acid test screening might be false positives.",2020,"Zhuang, G. H.; Shen, M. W.; Zeng, L. X.; Mi, B. B.; Chen, F. Y.; Liu, W. J.; Pei, L. L.; Qi, X.; Li, C.",Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi,2053265683,#5539,
,CZI,[Epidemiological analysis on a family cluster of COVID-19],10.3760/cma.j.cn112338-20200221-00147,,32133831,,"Objective: To understand the possible transmission route of a family cluster of COVID-19 in Zhengzhou and the potential infectivity of COVID-19 in incubation period, and provide scientific evidence for the timely control of infectious source and curb the spread of the epidemic. Methods: Epidemiological investigation was conducted for a family cluster of COVID-19 (8 cases) with descriptive epidemiological method, and respiratory tract samples of the cases were collected for the nucleic acid detection of 2019-nCoV by RT-PCR. Results: Two primary cases, which occurred on 31 January and 1 February, 2020, respectively, had a common exposure history in Wuhan. The other six family members had onsets on 30 January, 31 January, 1 February (three cases) and 3 February, 2020. Conclusions: In this family cluster of COVID-19, six family members were infected through common family exposure to the 2 primary cases. Five secondary cases had onsets earlier than or on the same day as the primary cases, indicating that COVID-19 is contagious in incubation period, and the home isolation in the early phase of the epidemic might lead to the risk of family cluster of COVID-19.",2020,"Qiu, Y. Y.; Wang, S. Q.; Wang, X. L.; Lu, W. X.; Qiao, D.; Li, J. B.; Gu, Y. Y.; Zeng, Y.; Chen, Y.; Bai, W. Z.; Xu, B. L.; Han, T. W.",Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi,2996261089,#4974,
,CZI,[Advances on presymptomatic or asymptomatic carrier transmission of COVID-19],10.3760/cma.j.cn112338-20200228-00207,,32141279,,"COVID-19 is rapidly spreading. Patients in incubation period and healthy carriers are possible sources for transmission. However, such sources of infection cannot be effectively identified due to the symptoms absent. The research evidence is very lacking so far, although there are a few studies suggesting that presymptomatic or asymptomatic carrier may cause COVID-19 transmission. Nearly half of the literature is in the state of preprint without peer review. The question of ""the degree to which presymptomatic or asymptomatic infections can transmit"" is not fully understood. There is an urgent need to screen infected carriers in larger close contacts or in the general population, and assess their risk for transmission.",2020,"Gao, W. J.; Li, L. M.",Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi,2052037214,#4683,
,CZI,Mental health survey of 230 medical staff in a tertiary infectious disease hospital for COVID-19,10.3760/cma.j.cn121094-20200219-00063,,32131151,,"Objective: To investigate the mental health of clinical first-line medical staff in COVID-19 epidemic and provide theoretical basis for psychological intervention. Method: The mental health status of the first-line medical staff was investigated by Self-rating Anxiety Acale (SAS) and Post-Traumatic Stress Disorder Self-rating Scale(PTSD-SS). From February 7 to 14, 2020, 246 medical staff were investigated who participated in the treatment of COVID-19 using cluster sampling , and received 230 responses, with a recovery rate of 93.5%. Results: The incidence of anxiety in medical staff was 23.04% (53/230), and the score of SAS was (42.91 ± 10.89). Among them, the incidence of severe anxiety, moderate anxiety and mild anxiety were 2.17% (5/230), 4.78% (11/230) and 16.09% (37/230), respectively. The incidence of anxiety in female medical staff was higher than that in male [25.67% (48/187) vs 11.63% (5/43), Z=-2.008, P=0.045], the score of SAS in female medical staff was higher than that in male [(43.78±11.12) vs (39.14 ± 9.01), t =-2.548, P=0.012]. The incidence of anxiety in nurses was higher than that in doctors [26.88% (43/160) vs 14.29% (10/70), Z=-2.066, P=0.039], and the score of SAS in nurses was higher than that in doctors [(44.84±10.42) vs (38.50±10.72), t =-4.207, P<0.001]. The incidence of stress disorder in medical staff was 27.39% (63/230), and the score of PTSD-SS was (42.92 ± 17.88). The score of PTSD-SS in female medical staff was higher than that of male [(44.30±18.42) vs(36.91 ± 13.95), t=-2.472, P=0.014]. Conclusions: In COVID-19 epidemic, the incidence of anxiety and stress disorder is high among medical staff. Medical institutions should strengthen the training of psychological skills of medical staff. Special attention should be paid to the mental health of female nurses.",2020,"Huang, J. Z.; Han, M. F.; Luo, T. D.; Ren, A. K.; Zhou, X. P.",Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi,2393057990,#4557,
,CZI,Standardized diagnosis and treatment of colorectal cancer during the outbreak of novel coronavirus pneumonia in Renji hospital,10.3760/cma.j.cn441530-20200217-00057,,32084676,,"Novel coronavirus pneumonia (NCP) is currently raging in China. It has been proven that NCP can be transmitted from human to human and cause hospital infection, which seriously threatens surgical staffs and inpatients. Although colorectal surgery is not a front-line subject in the fight against the epidemic, but in this special situation, now it is a difficult task that with the premise of how to maximize the protection for patients and their families, health of medical staff, and the safety of wards and hospitals, we can provide the highest quality medical services to ensure the orderly development of previous clinical work. Referring to the ""Diagnosis and Treatment Scheme for NCP (Trial Version 4 and 5)"" and combining the actual practice situation in our hospital with the ""Summary of New Coronavirus Files of Shanghai Renji Hospital"", we summarize how to carry out the clinical practice of colorectal surgery under the situation of the prevention and control of the NCP epidemiology, meanwhile under such situation aiming the procedure of diagnose and treatment for emergency patients with colorectal tumor, we share the experiences of the diagnosis of colorectal tumor, the management of patients with colorectal cancer who are scheduled to be admitted for surgery, the protection of wards, the perioperative management. More importantly, we introduce in detail the operative management and perioperative management of colorectal surgery patients suspected or diagnosed with new coronary pneumonia, including prevention and control measures for medical staff, operating rooms and surgical instruments. The main points are as follows: (1) Multidisciplinary team (MDT) must be run through the diagnosis and treatment of colorectal cancer. The members include not only routine departments, but also respiratory department and infectious department. (2) Colonoscopy examination may cause cross infection of NCP to patients and doctors. Therefore, it is prior to examine the emergency cases and life-threatening patients (bleeding, obstruction, gastrointestinal foreign bodies, etc.). If the emergent patients (intestinal obstruction) with suspected or confirmed NCP, the surgeons must perform emergency surgery, and intestinal decompressive tube through colonoscopy is not recommended. (3) The colorectal cancer patients with suspected or confirmed NCP should be placed in the isolated room with separate medical devices, and the operative room with negative pressure (under-5 Pa) must be separated. All disposable medical items, body fluids and feces of the patients in perioperative periods must be unified disposed according to the medical waste standard. (4) The surgical medical workers who process colorectal cancer patients with NCP must be protected by three-level. After operation, the medical workers must receive medical observation and be isolated for 14 days. We hope our ""Renji experience"" will be beneficial to colleagues.",2020,"Luo, Y.; Zhong, M.",Zhonghua Wei Chang Wai Ke Za Zhi,2009124022,#1958,
,CZI,Thinking of treatment strategies for colorectal cancer patients in tumor hospitals under the background of coronavirus pneumonia,10.3760/cma.j.cn441530-20200217-00058,,32084675,,"In December 2019, a new outbreak of coronavirus pneumonia began to occur. Its pathogen is 2019-nCoV, which has the characteristics of strong infectivity and general susceptibility. The current situation of prevention and control of new coronavirus pneumonia is severe. In this context, as front-line medical workers bearing important responsibilities and pressure, while through strict management strategy, we can minimize the risk of infection exposure. By summarizing the research progress and guidelines in recent years in the fields of colorectal cancer disease screening, treatment strategies(including early colorectal cancer, locally advanced colorectal cancer, obstructive colorectal cancer, metastatic colorectal cancer and the treatment of patients after neoadjuvant therapy), the choice of medication and time limit for adjuvant therapy, the protective measures for patients undergoing emergency surgery, the re-examination of postoperative patients and the protection of medical staff, etc., authors improve treatment strategies in order to provide more choices for patients to obtain the best treatment under the severe epidemic situation of new coronavirus pneumonia. Meanwhile we hope that it can also provide more timely treatment modeling schemes for colleagues.",2020,"Hu, X. H.; Niu, W. B.; Zhang, J. F.; Li, B. K.; Yu, B.; Zhang, Z. Y.; Zhou, C. X.; Zhang, X. N.; Gao, Y.; Wang, G. Y.",Zhonghua Wei Chang Wai Ke Za Zhi,641660370,#1625,
,CZI,[Recommendations for the regulation of medical practices of burn treatment during the outbreak of the coronavirus disease 2019],10.3760/cma.j.cn501120-20200224-00083,,32111114,,"2019 novel coronavirus (2019-nCoV) is one of the beta coronaviruses and was identified as the pathogen of the severe ""coronavirus disease 2019 (COVID-19)"" in 2019. China has formally included the 2019-nCoV in the statutory notification and control system for infectious diseases according to the Law of the People's Republic of China on the Prevention and Treatment of Infectious Diseases. Currently, the national defending actions on the 2019-nCoV in China is in a critical period. Burn Department is also confronted with risk of infection by the 2019-nCoV. According to the guidelines on the diagnosis and treatment of COVID-19 (6(th) trial edition), the latest relative literature at home and abroad, the features of the COVID-19, recommendations for the COVID-19 prevention and control issued by the National Health Commission of China, and management experience of diagnosis and treatment in the related disciplines, we put forward recommendations for the medical practices of burn treatment during the outbreak of the COVID-19 in outpatient and emergency treatment, inpatient treatment, operation and ward management, etc. We hope these recommendations could benefit the professionals of the same occupation as us and related hospital managers, improve the treatment of burn during the outbreak of the COVID-19, and avoid or reduce the risk of infection of medical staff .",2020,"Ma, S. Y.; Yuan, Z. Q.; Peng, Y. Z.; Luo, Q. Z.; Song, H. P.; Xiang, F.; Tan, J. L.; Zhou, J. Y.; Li, N.; Hu, G. Z.; Luo, G. X.",Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns,2773264689,#2897,
,CZI,Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies,10.3760/cma.j.cn501120-20200224-00088,,32114747,,"Corona Virus Disease 2019 (COVID-19) has seriously affected the treatment of patients and social stability. In the later stage of disease, some COVID-19 patients may develop into acute respiratory distress syndrome or even multiple organ failure. However, one of the most important mechanism underlying the deterioration of disease is cytokine storm. At present, some therapies such as interleukin-6 antibody blocker, stem cell therapy, and transfusion of convalescent plasma have been applied to counteract the cytokine storm and have made some progress. This article reviews the influences of cytokine storm syndrome on the COVID-19 and the corresponding immunotherapies to resist cytokine storm.",2020,"Chen, C.; Zhang, X. R.; Ju, Z. Y.; He, W. F.",Zhonghua Shao Shang Za Zhi,2378303257,#3070,
,CZI,[COVID-19 complicated with DIC: 2 cases report and literatures review],10.3760/cma.j.issn.0253-2727.2020.0001,,32133824,,,2020,"Wang, Y. D.; Zhang, S. P.; Wei, Q. Z.; Zhao, M. M.; Mei, H.; Zhang, Z. L.; Hu, Y.",Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi,2980953248,#5291,
,CZI,"[Characteristics, causes, diagnosis and treatment of coagulation dysfunction in patients with COVID-19]",10.3760/cma.j.issn.0253-2727.2020.0002,,32133825,,,2020,"Mei, H.; Hu, Y.",Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi,2123029822,#4902,
,CZI,2019-nCoV: new challenges from coronavirus,10.3760/cma.j.issn.0253-9624.2020.0001,,32023682,,"The outbreak of pneumonia caused by the novel coronavirus 2019-nCoV in Wuhan, Hubei province of China, at the end of 2019 shaped tremendous challenges to China's public health and clinical treatment. The virus belongs to the β genus Coronavirus in the family Corornaviridae, and is closely related to SARS-CoV and MERS-CoV, causing severe symptoms of pneumonia. The virus is transmitted through droplets, close contact, and other means, and patients in the incubation period could potentially transmit the virus to other persons. According to current observations, 2019-nCoV is weaker than SARS in pathogenesis, but has stronger transmission competence; it's mechanism of cross-species spread might be related with angiotensin-converting enzyme Ⅱ (ACE2), which is consistent with the receptor SARS-CoV. After the outbreak of this disease, Chinese scientists invested a lot of energy to carry out research by developing rapid diagnostic reagents, identifying the characters of the pathogen, screening out clinical drugs that may inhibit the virus, and are rapidly developing vaccines. The emergence of 2019-nCoV reminds us once again of the importance of establishing a systematic coronavirus surveillance network. It also poses new challenges to prevention and control of the emerging epidemic and rapidly responses on scientific research.",2020,"Tian, H. Y.",Zhonghua Yu Fang Yi Xue Za Zhi,3006243359,#270,
,CZI,2019-nCoV: new challenges from coronavirus,10.3760/cma.j.issn.0253-9624.2020.0001,,,,"The outbreak of pneumonia caused by the novel coronavirus 2019-nCoV in Wuhan, Hubei province of China, at the end of 2019 shaped tremendous challenges to China's public health and clinical treatment. The virus belongs to the &beta; genus Coronavirus in the family Corornaviridae, and is closely related to SARS-CoV and MERS-CoV, causing severe symptoms of pneumonia. The virus is transmitted through droplets, close contact, and other means, and patients in the incubation period could potentially transmit the virus to other persons. According to current observations, 2019-nCoV is weaker than SARS in pathogenesis, but has stronger transmission competence; it's mechanism of cross-species spread might be related with angiotensin-converting enzyme &#8545; (ACE2), which is consistent with the receptor SARS-CoV. After the outbreak of this disease, Chinese scientists invested a lot of energy to carry out research by developing rapid diagnostic reagents, identifying the characters of the pathogen, screening out clinical drugs that may inhibit the virus, and are rapidly developing vaccines. The emergence of 2019-nCoV reminds us once again of the importance of establishing a systematic coronavirus surveillance network. It also poses new challenges to prevention and control of the emerging epidemic and rapidly responses on scientific research.",2020,"TIAN, Huai Yu",Chinese Journal of Preventive Medicine,3006243359,#270,
,CZI,Be alert to superposed effect of seasonal influenza while fighting against novel coronavirus pneumonia,10.3760/cma.j.issn.0253-9624.2020.0002,,32040985,,"The novel coronavirus pneumonia (NCP) continues to spread throughout the country, and the prevention and control of the epidemic has entered a critical period. However, southern cities with severe outbreaks are about to enter the seasonal influenza season. We should strengthen the epidemiological investigation, optimize the laboratory testing strategy, take effective measures, strengthen the prevention and control of influenza epidemic, and minimize the interference to the new coronavirus epidemic.",2020,"Li, T. G.; Wang, M.",Zhonghua Yu Fang Yi Xue Za Zhi,2015989058,#696,
,CZI,"The network investigation on knowledge, attitude and practice about Novel coronavirus pneumonia of the residents in Anhui Province",10.3760/cma.j.issn.0253-9624.2020.0004,,32064854,,"Objective: To analyze the current situation of the knowledge, attitudes and practice about Novelcoronavirus pneumonia (NCP) of the residents in Anhui Province. Methods: Anonymous network sampling survey was carried out with an electronic questionnaire that designed by the questionnaire star, and a total of 4016 subjects from Anhui province were investigated. The content of the survey includes that the basic information of subjects,the residents' knowledge, attitudes and practice about NCP, as well as their satisfaction with the prevention and control measures adopted by the government and health authorities and the suggestions on future prevention. The questionnaire doesn't involve any privacy information, and all questions were mandatory to ensure the response rate. Results: The M (P(25), P(75)) age the 4016 subjects was 21 (19, 24), and the ranging from 7 to 80 years old. The number of males was1431(35.6%). Social networking tools such as WeChat and QQ were the main sources of epidemic information for residents (97.8%, 3 929 respondents). Residents have a high awareness rate of the main symptoms, transmission routes, using of masks, hand washing and treatment information of NCP, while a low awareness rate of the atypical symptoms. 92.6% of the subjects (n=3 720) think that the outbreak was scary. In terms of psychological behavior scores, the results showed that female (9.38±4.81), the urban (9.37±5.02) and the medical workers (10.79±5.19) had a poorer mental health than the male (8.45±5.00) , the rural (8.71±4.75) and the non-medical workers (the students: 8.85±4.83; public institude workers: 9.02±5.08; others: 8.97±5.39) (P < 0.05). 71.9% of the residents (n=2 887)were satisfied with the local epidemic control measures. The residents took various of the measures to prevent and control the epidemic. The ratio of residents that could achieve ""no gathering and less going out"" , ""wear masks when going out"" and ""do not go to crowded and closed places"" was up to 97.4% (n=3 913), 93.6% (n=3758) and 91.5% (n=3 673) respectively. Conclusion: The residents in Anhui province have a good KAP about NCP, yet it is necessary to strengthen the community publicity, the mental health maintenance of residents and students' health education.",2020,"Chen, Y.; Jin, Y. L.; Zhu, L. J.; Fang, Z. M.; Wu, N.; Du, M. X.; Jiang, M. M.; Wang, J.; Yao, Y. S.",Zhonghua Yu Fang Yi Xue Za Zhi,2363410972,#2333,
,CZI,Analysis of the first cluster of cases in a family of novel coronavirus pneumonia in Gansu Province,10.3760/cma.j.issn.0253-9624.2020.0005,,32064855,,"The epidemiological history and clinical characteristics of 7 cases of COVID-19 and 1 case of close contact in the first family aggregation epidemic of COVID-19 in Gansu Province were analyzed. The first patient A developed on January 22, 2020, with a history of residence in Wuhan, and confirmed severe cases of NCP on January 24, 2020; patient B, on January 23, 2020, diagnosed on January 31, severe cases; patient C, asymptomatic, diagnosed on January 27; patient D, asymptomatic, diagnosed on January 27; patient E, on January 24, diagnosed on January 28; patient F, asymptomatic, diagnosed on January 31; Patient G was asymptomatic and was diagnosed on January 31. In close contact, H was asymptomatic, PCR test was negative and asymptomatic, and he was discharged early. Among the 7 patients, 1 case died of (B) aggravation, and the other patients' condition was effectively controlled after active treatment. Except for the discharged cases, 5 cases were positive for COVID-19 specific IgM antibody and 1 case was negative. In this clustering outbreak, 4 patients remained asymptomatic, but PCR and IgM antibodies were positive, indicating that asymptomatic patients may be the key point to control the epidemic. Specific IgM antibody screening for patients whose pharyngeal swab nucleic acid test is negative but with ground glass-like lung lesions is very important for early detection and early isolation.",2020,"Bai, S. L.; Wang, J. Y.; Zhou, Y. Q.; Yu, D. S.; Gao, X. M.; Li, L. L.; Yang, F.",Zhonghua Yu Fang Yi Xue Za Zhi,3005670878,#2370,
,CZI,Analysis of the first cluster of cases in a family of novel coronavirus pneumonia in Gansu Province,10.3760/cma.j.issn.0253-9624.2020.0005,,32064855,,"The epidemiological history and clinical characteristics of 7 cases of COVID-19 and 1 case of close contact in the first family aggregation epidemic of COVID-19 in Gansu Province were analyzed. The first patient A developed on January 22, 2020, with a history of residence in Wuhan, and confirmed severe cases of NCP on January 24, 2020; patient B, on January 23, 2020, diagnosed on January 31, severe cases; patient C, asymptomatic, diagnosed on January 27; patient D, asymptomatic, diagnosed on January 27; patient E, on January 24, diagnosed on January 28; patient F, asymptomatic, diagnosed on January 31; Patient G was asymptomatic and was diagnosed on January 31. In close contact, H was asymptomatic, PCR test was negative and asymptomatic, and he was discharged early. Among the 7 patients, 1 case died of (B) aggravation, and the other patients' condition was effectively controlled after active treatment. Except for the discharged cases, 5 cases were positive for COVID-19 specific IgM antibody and 1 case was negative. In this clustering outbreak, 4 patients remained asymptomatic, but PCR and IgM antibodies were positive, indicating that asymptomatic patients may be the key point to control the epidemic. Specific IgM antibody screening for patients whose pharyngeal swab nucleic acid test is negative but with ground glass-like lung lesions is very important for early detection and early isolation.;",2020,"Bai, Shaoli; Wang, Jianyun; Zhou, Yingquan; Yu, Desheng; Gao, Xiaomin; Li, Lingling; Yang, Fan",Chinese Journal of Preventive Medicine,3005670878,#2370,
,CZI,Early containment strategies and core measures for prevention and control of novel coronavirus pneumonia in China,10.3760/cma.j.issn.0253-9624.2020.03.003,,32064856,,"In December 2019, novel coronavirus pneumonia epidemic occurred in Wuhan, Hubei Province, and spread rapidly across the country. In the early stages of the epidemic, China adopted the containment strategy and implemented a series of core measures around this strategic point, including social mobilization, strengthening case isolation and close contacts tracking management, blocking epidemic areas and traffic control to reduce personnel movements and increase social distance, environmental measures and personal protection, with a view to controlling the epidemic as soon as possible in limited areas such as Wuhan. This article summarizes the background, key points and core measures in the country and provinces. It sent prospects for future prevention and control strategies.",2020,"Chen, W.; Wang, Q.; Li, Y. Q.; Yu, H. L.; Xia, Y. Y.; Zhang, M. L.; Qin, Y.; Zhang, T.; Peng, Z. B.; Zhang, R. C.; Yang, X. K.; Yin, W. W.; An, Z. J.; Wu, D.; Yin, Z. D.; Li, S.; Chen, Q. L.; Feng, L. Z.; Li, Z. J.; Feng, Z. J.",Zhonghua Yu Fang Yi Xue Za Zhi,2995124404,#1159,
,CZI,Urgent research agenda for the novel coronavirus epidemic: transmission and non-pharmaceutical mitigation strategies,10.3760/cma.j.issn.0254-6450.2020.02.001,,32026672,,,2020,"Strategy; Policy Working Group for, Ncip Epidemic Response",Zhonghua Liu Xing Bing Xue Za Zhi,3002539152,#428,
,CZI,An update on the epidemiological characteristics of novel coronavirus pneumonia（COVID-19）,10.3760/cma.j.issn.0254-6450.2020.02.002,,32057211,,"Through literature review and group discussion, Special Expert Group for Control of the Epidemic of Novel Coronavirus Pneumonia of the Chinese Preventive Medicine Association formulated an update on the epidemiological characteristics of novel coronavirus pneumonia (NCP). The initial source of the 2019 novel coronavirus (2019-nCoV) was the Huanan seafood market in Wuhan, Hubei province, China, with pangolins as a potential animal host. Currently the main source of infection is NCP patients, and asymptomatic carriers may also be infectious. The virus is believed transmitted mostly via droplets or contact. People are all generally susceptible to the virus. The average incubation period was 5.2 days, and the basic reproductive number R(0) was 2.2 at the onset of the outbreak. Most NCP patients were clinically mild cases. The case fatality rate was 2.38%, and elderly men with underlying diseases were at a higher risk of death. Strategies for prevention and control of NCP include improving epidemic surveillance, quarantining the source of infection, speeding up the diagnosis of suspected cases, optimizing the management of close contacts, tightening prevention and control of cluster outbreaks and hospital infection, preventing possible rebound of the epidemic after people return to work from the Chinese Spring Festival holiday, and strengthening community prevention and control.",2020,"Special Expert Group for Control of the Epidemic of Novel Coronavirus Pneumonia of the Chinese Preventive Medicine, Association",Zhonghua Liu Xing Bing Xue Za Zhi,,#915,
,CZI,The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China,10.3760/cma.j.issn.0254-6450.2020.02.003,,32064853,,"Objective: An outbreak of 2019 novel coronavirus diseases (COVID-19) in Wuhan, China has spread quickly nationwide. Here, we report results of a descriptive, exploratory analysis of all cases diagnosed as of February 11, 2020. Methods: All COVID-19 cases reported through February 11, 2020 were extracted from China's Infectious Disease Information System. Analyses included: 1) summary of patient characteristics; 2) examination of age distributions and sex ratios; 3) calculation of case fatality and mortality rates; 4) geo-temporal analysis of viral spread; 5) epidemiological curve construction; and 6) subgroup analysis. Results: A total of 72 314 patient records-44 672 (61.8%) confirmed cases, 16 186 (22.4%) suspected cases, 10567 (14.6%) clinical diagnosed cases (Hubei only), and 889 asymptomatic cases (1.2%)-contributed data for the analysis. Among confirmed cases, most were aged 30-79 years (86.6%), diagnosed in Hubei (74.7%), and considered mild (80.9%). A total of 1 023 deaths occurred among confirmed cases for an overall case-fatality rate of 2.3%. The COVID-19 spread outward from Hubei sometime after December 2019 and by February 11, 2020, 1 386 counties across all 31 provinces were affected. The epidemic curve of onset of symptoms peaked in January 23-26, then began to decline leading up to February 11. A total of 1 716 health workers have become infected and 5 have died (0.3%). Conclusions: The COVID-19 epidemic has spread very quickly. It only took 30 days to expand from Hubei to the rest of Mainland China. With many people returning from a long holiday, China needs to prepare for the possible rebound of the epidemic.",2020,"Novel Coronavirus Pneumonia Emergency Response Epidemiology, Team",Zhonghua Liu Xing Bing Xue Za Zhi,3005943294,#1123,
,CZI,"Cluster investigation Technical Guidelines for the 2019 Novel Coronavirus Pneumonia (COVID-19), China (1st Trial Version)",10.3760/cma.j.issn.0254-6450.2020.03.001,,32061201,,,2020,"Epidemiology Working Group, Strategy; Policy Working Group for Ncip Epidemic Response, Chinese Center for Disease Control; Prevention",Zhonghua Liu Xing Bing Xue Za Zhi,3002539152,#1012,
,CZI,Consideration on the strategies during epidemic stage changing from emergency response to continuous prevention and control,10.3760/cma.j.issn.0254-6450.2020.03.003,,32088947,,,2020,"Special Expert Group for Control of the Epidemic of Novel Coronavirus Pneumonia of the Chinese Preventive Medicine, Association",Zhonghua Liu Xing Bing Xue Za Zhi,2335493203,#1765,
,CZI,"Interpretation of ""Guidelines for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Infection by the National Health Commission (Trial Version 5)""",10.3760/cma.j.issn.0376-2491.2020.0001,,32033513,,"the National Health Commission of the People's Republic of China publish the guidelines for the diagnosis and treatment of novel coronavirus (2019-nCoV) infection (trial version 5) .With the awareness and understanding of the disease, the guidelines have been revised for recognize, treat, and prevent diseases. Then, what are the contents of the fifth edition of the guide issued updated compared to the fourth edition, now, learn together.",2020,"Lin, L.; Li, T. S.",Zhonghua Yi Xue Za Zhi,3004824173,#479,
,CZI,"The way to reduce the""false negative results""of 2019 novel coronavirus nucleic acid detection",10.3760/cma.j.issn.0376-2491.2020.0008,,32072795,,,2020,"Zhang, R.; Li, J. M.",Zhonghua Yi Xue Za Zhi,3005656138,#1257,
,CZI,Suggestions for disinfection of ophthalmic examination equipment and protection of ophthalmologist against 2019 novel coronavirus infection,10.3760/cma.j.issn.0412-4081.2020.0001,,32035428,,"At present, the prevention and treatment of 2019 Novel Coronavirus (2019-nCoV) in China has reached a critical stage. It is extremely important to disinfect ophthalmic examination instruments and protect ophthalmic medical care during the epidemic period to reduce cross-infection in clinical practice and reduce the infection risk of ophthalmic medical staff. (Chin J Ophthalmol, 2020, 56: 0001).",2020,"Zhang, M. C.; Xie, H. T.; Xu, K. K.; Cao, Y.",Zhonghua Yan Ke Za Zhi,2982939398,#555,
,CZI,Suggestions from ophthalmic experts on eye protection during the novel coronavirus pneumonia epidemic,10.3760/cma.j.issn.0412-4081.2020.0002,,32061202,,,2020,"Society of Public Health Ophthalmology, Chinese Preventive Medicine Association; Beijing Ophthalmological, Society; Youth Committee of Beijing Ophthalmological, Society",Zhonghua Yan Ke Za Zhi,2166867592,#1006,
,CZI,Recommendations for general surgery clinical practice in novel coronavirus pneumonia situation,10.3760/cma.j.issn.0529-5815.2020.0001,,32057212,,"Novel coronavirus pneumonia (NCP) is a highly infectious disease, has a long incubation period and a variety of clinical manifestations, which has a significant impact on public health and life. Afterwards, scientific and standardized work processing during the epidemic is of great significance for prevention and control. In order to implement the central government's decision-making deployment and defeat the NCP as soon as possible, we had focused on the key points in the clinical work of general surgery according to latest relevant guidelines, literature and experience in epidemic prevention. Finally, we drafted the prevention and control strategies and recommendations to make a reference for medical staff of general surgery to fight NCP.",2020,"TAO, Kai xiong; ZHANG, Bi xiang; ZHANG, Peng; ZHU, Peng; WANG, Guo bin; CHEN, Xiao ping",Chinese Journal of Surgery,3006604045,#1027,
,CZI,Countermeasures and treatment for aortic acute syndrome with novel coronavirus pneumonia,10.3760/cma.j.issn.0529-5815.2020.0002,,32066206,,"The novel coronavirus pneumonia (NCP) has cost a great loss to the health and economic property of Chines people. Under such a special circumstance, how to deal with such patients with acute aortic syndrome has become a serious challenge. Rapid diagnosis of concomitant NCP, safe and effective transportation, implementation of the interventional procedure, protection of vascular surgical team and postoperative management and follow-up of such patients have become urgent problems for us. Combined with the latest novel government documents, the literature and the experiences from Wuhan, we answered the above questions briefly and plainly. It also hopes to inspire the national vascular surgeons to manage critical emergencies in vascular surgery and even routine vascular diseases with NCP, as a final point to limit the severe epidemic situation, and minimize the damage of NCP.",2020,"Si, Y.; Sun, X. F.; Zhong, M.; Yue, J. N.; Fu, W. G.",Zhonghua Wai Ke Za Zhi,2132260239,#1176,
,CZI,Facing the pandemic of 2019 novel coronavirus infections: the pediatric perspectives,10.3760/cma.j.issn.0578-1310.2020.0001,,32023678,,,2020,"Fang, F.; Luo, X. P.",Zhonghua Er Ke Za Zhi,3005240180,#325,
,CZI,First case of 2019 novel coronavirus infection in children in Shanghai,10.3760/cma.j.issn.0578-1310.2020.0002,,32023679,,,2020,"Cai, J. H.; Wang, X. S.; Ge, Y. L.; Xia, A. M.; Chang, H. L.; Tian, H.; Zhu, Y. X.; Wang, Q. R.; Zeng, J. S.",Zhonghua Er Ke Za Zhi,3004790666,#340,
,CZI,Prevention and control program on 2019 novel coronavirus infection in Children's digestive endoscopy center,10.3760/cma.j.issn.0578-1310.2020.0003,,32023683,,,2020,"Subspecialty Group of Gastroenterology, the Society of Pediatrics Chinese Medical Association",Zhonghua Er Ke Za Zhi,3004896587,#272,
,CZI,"Recommendations for the diagnosis, prevention and control of the 2019 novel coronavirus infection in children (first interim edition)",10.3760/cma.j.issn.0578-1310.2020.0004,,32035429,,,2020,"Society of Pediatrics, Chinese Medical Association; Editorial Board, Chinese Journal of Pediatrics",Zhonghua Er Ke Za Zhi,3004790666,#558,
,CZI,Frist case of severe childhood novel coronavirus pneumonia in China,10.3760/cma.j.issn.0578-1310.2020.0005,,32045966,,"1例主诉为""间断腹泻、呕吐6 d，发热伴呼吸急促半天""的患儿就诊于武汉儿童医院重症医学科，诊断为儿童危重型新型冠状病毒肺炎（NCP）。以""新型冠状病毒肺炎""""儿童""""危重型"" 为关键词检索截至2020年2月8日中国知网、维普网、万方等相关数据库，未见报道。本例为中国首例危重型NCP患儿，以消化道症状起病，早期呼吸道症状 不明显，快速进展为急性呼吸窘迫综合征、脓毒症休克并伴有急性肾衰竭。患儿早期连续2次咽拭子2019新型冠状病毒（2019-nCoV）核酸检测阴性。 对于重症疑似病例，建议采集下呼吸道样本或重复采集上呼吸道样本进行检测。体外连续血液净化技术可尽早应用到危重型NCP患儿的救治中。",2020,"Chen, F.; Liu, Z. S.; Zhang, F. R.; Xiong, R. H.; Chen, Y.; Cheng, X. F.; Wang, W. Y.; Ren, J.",Zhonghua Er Ke Za Zhi,3004790666,#790,
,CZI,First case of severe childhood novel coronavirus pneumonia in China,10.3760/cma.j.issn.0578-1310.2020.0005,,32045967,,,2020,"CHEN, Feng; LIU, Zhi sheng; ZHANG, Fu rong; XIONG, Rui hua; CHEN, Yang; CHENG, X Feng; WANG, Wen yong; REN, Jie",Chinese Journal of Pediatrics,3004790666,#3588,
,CZI,2019-novel coronavirus infection in a three-month-old baby,10.3760/cma.j.issn.0578-1310.2020.0006,,32043842,,,2020,"Zhang, Y. H.; Lin, D. J.; Xiao, M. F.; Wang, J. C.; Wei, Y.; Lei, Z. X.; Zeng, Z. Q.; Li, L.; Li, H. A.; Xiang, W.",Zhonghua Er Ke Za Zhi,2951323607,#699,
,CZI,Analysis of CT features of 15 Children with 2019 novel coronavirus infection,10.3760/cma.j.issn.0578-1310.2020.0007,,32061200,,"Objective: To explore imaging characteristics of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: A retrospective analysis was performed on clinical data and chest CT images of 15 children diagnosed with 2019-nCoV. They were admitted to the third people's Hospital of Shenzhen from January 16 to February 6, 2020. The distribution and morphology of pulmonary lesions on chest CT images were analyzed. Results: Among the 15 children, there were 5 males and 10 females, aged from 4 to 14 years old. Five of the 15 children were febrile and 10 were asymptomatic on first visit. The first nasal or pharyngeal swab samples in all the 15 cases were positive for 2019-nCoV nucleic acid. For their first chest CT images, 6 patients had no lesions, while 9 patients had pulmonary inflammation lesions. Seven cases of small nodular ground glass opacities and 2 cases of speckled ground glass opacities were found. After 3 to 5 days of treatment, 2019-nCoV nucleic acid in a second respiratory sample turned negative in 6 cases. Among them, chest CT images showed less lesions in 2 cases, no lesion in 3 cases, and no improvement in 1 case. Other 9 cases were still positive in a second nucleic acid test. Six patients showed similar chest CT inflammation, while 3 patients had new lesions, which were all small nodular ground glass opacities. Conclusions: The early chest CT images of children with 2019-nCoV infection are mostly small nodular ground glass opacities. The clinical symptoms of children with 2019-nCoV infection are nonspecific. Dynamic reexamination of chest CT and nucleic acid are important.",2020,"Feng, K.; Yun, Y. X.; Wang, X. F.; Yang, G. D.; Zheng, Y. J.; Lin, C. M.; Wang, L. F.",Zhonghua Er Ke Za Zhi,3004906315,#1011,
,CZI,Clinical and epidemiological characteristics of 34 children with 2019 novel coronavirus infection in Shenzhen,10.3760/cma.j.issn.0578-1310.2020.0008,,32062875,,"Objective: To describe the characteristics of clinical manifestations and epidemiology of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: All 34 children with laboratory-confirmed 2019-nCoV infection by quantitative real-time reverse transcription-PCR through nasopharyngeal swab specimens were admitted to the Third People's Hospital of Shenzhen from January 19 to Febuary 7, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. Results: Among the 34 cases, 14 were males, and 20 were females. The median age was 8 years and 11 months. No patients had underlying diseases. There were 28 children (82%) related with a family cluster outbreak. There were 26 children (76%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 22 (65%) common cases, 9 (26%) mild cases and 3 (8.8%) asymptomatic cases. No severe or critical cases were identified. The most common symptoms were fever (17 cases, 50%) and cough (13 cases, 38% ). In the 34 cases, the white blood cell counts of 28 cases (82%) were normal. Five cases had white blood cell counts more than 10×10(9)/L. One case had white blood cell counts less than 4×10(9)/L. Neutropenia and lymphopenia was found in one case, respectively. C-reactive protein levels and erythrocyte sedimentation rates were elevated in 1 and 5 case, respectively. Elevated procalcitonin was found in 1 case and D-Dimer in 3 cases. The levels of lactic dehydrogenase (LDH) were more than 400 U/L in 10 cases. The CT images of these patients showed bilateral multiple patchy or nodular ground-glass opacities and/or infiltrating shadows in middle and outer zone of the lung or under the pleura. Twenty patients were treated with lopinavir and ritonavir. Glucocorticoids and immunoglobulin were not used in any cases. All the cases improved and were discharged from hospital. Further following up was need. Conclusions: The clinical manifestations in children with 2019-nCoV infection are non-specific and are milder than that in adults. Chest CT scanning is heplful for early diagnosis. Children's infection is mainly caused by family cluster outbreak and imported cases. Family daily prevention is the main way to prevent 2019-nCoV infection.",2020,"Wang, X. F.; Yuan, J.; Zheng, Y. J.; Chen, J.; Bao, Y. M.; Wang, Y. R.; Wang, L. F.; Li, H.; Zeng, J. X.; Zhang, Y. H.; Liu, Y. X.; Liu, L.",Zhonghua Er Ke Za Zhi,3002108456,#1004,
,CZI,First case of neonate infected with novel coronavirus pneumonia in China,10.3760/cma.j.issn.0578-1310.2020.0009,,32065520,,,2020,"Zeng, L. K.; Tao, X. W.; Yuan, W. H.; Wang, J.; Liu, X.; Liu, Z. S.",Zhonghua Er Ke Za Zhi,3004790666,#1084,
,CZI,Noninvasive Respiratory Support for Novel Coronavirus Pneumonia: Enough is Enough,10.3760/cma.j.issn.0578-1426.2020.0006,,32129582,,,2020,"Pan, C.; Zhang, W.; Xia, J. A.; Liu, H.; Du, B.; Qiu, H. B.",Zhonghua Nei Ke Za Zhi,3005255913,#4355,
,CZI,Diagnosis and clinical management of 2019 novel coronavirus infection: an operational recommendation of Peking Union Medical College Hospital (V2.0),10.3760/cma.j.issn.0578-1426.2020.03.003,,32023681,,"Since December 2019, China has been experiencing an outbreak of new infectious disease caused by 2019 novel coronavirus (2019-nCoV). The clinical features include fever, coughing, shortness of breath, and inflammatory pulmonary infiltration revealed by X ray. China rapidly identified 2019-nCoV-related pneumonia a statutory infectious disease. To standardize the diagnosis and treatment of this new infectious disease, operational guidelines for the diagnosis and management of 2019-nCoV infection is accomplished by Peking Union Medical College Hospital.",2020,"Working Group of Novel Coronavirus, Peking Union Medical College Hospital",Zhonghua Nei Ke Za Zhi,3005477624,#259,
,CZI,Efficient management of novel coronavirus pneumonia by efficient prevention and control in scientific manner,10.3760/cma.j.issn.1001-0939.2020.0001,,32023684,,"At the end of 2019, sporadic and clustered case with ""pneumonia of unknown origin"" emerged in Wuhan, Hubei province. The causative pathogen was quickly confirmed as ""2019-nCoV"" . The epidemic soon spread throughout the country and became a pandemic in over a month. Government and medical institutions across the country mobilized all kinds of resources and took a variety of measures to actively treat patients and stop the epidemic. Based on current studies, the author summarized the clinical characteristics and evolution of the novel viral pneumonia, and proposed the key points of diagnosis and treatment, the scientific management of both confirmed and suspected cases, and the scientific management of disease prevention and control.",2020,"Gao, Z. C.",Zhonghua Jie He He Hu Xi Za Zhi,2115137097,#324,
,CZI,Potential antiviral therapeutics for 2019 Novel Coronavirus,10.3760/cma.j.issn.1001-0939.2020.0002,,32023685,,"The recent outbreak of respiratory illness in Wuhan, China is caused by a novel coronavirus, named 2019-nCoV, which is genetically close to a bat-derived coronavirus. 2019-nCoV is categorized as beta genus coronavirus, same as the two other strains - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir / ritonavir, lopinavir / ritonavir combined with interferon-β, convalescent plasma, and monoclonal antibodies. But the efficacy and safety of these drugs for 2019-nCoV pneumonia patients need to be assessed by further clinical trials.",2020,"Li, H.; Wang, Y. M.; Xu, J. Y.; Cao, B.",Zhonghua Jie He He Hu Xi Za Zhi,3004878749,#309,
,CZI,Early detection and disease assessment of patients with novel coronavirus pneumonia,10.3760/cma.j.issn.1001-0939.2020.0003,,32023686,,"In December 2019, the outbreak of novel coronavirus (2019- nCoV) in wuhan, China, attracting attention worldwidely. The novel coronavirus has the characteristics of rapid transmission, atypical clinical symptoms, and easy to affect both lungs, leading to missed diagnosis and misdiagnosis, as well as difficult to detection and assessment at early stage. Fever, cough, myalgia, weakness, dyspnea and imagings may be helpful for the early detection of novel coronavirus pneumonia. At the same time, the rate of disease progression, fever, CT manifestations, hypoxia degree, age, basic diseases, and laboratory indicators can also be used to evaluate the severity of the novel coronavirus pneumonia.",2020,"Zhou, L.; Liu, H. G.",Zhonghua Jie He He Hu Xi Za Zhi,2481602709,#247,
,CZI,Pulmonary rehabilitation guidelines in the principle of 4S for patients infected with 2019 novel coronavirus (2019-nCoV),10.3760/cma.j.issn.1001-0939.2020.0004,,32023687,,"A recent epidemic of pneumonia cases in Wuhan China was caused by a novel coronavirus with strong infectivity, the 2019 novel coronavirus (2019-nCoV). The article provides the pulmonary rehabilitation (PR) methods in the principle of 4S (simple, safe, satisfy, save) for patients with pneumonia caused by the novel coronavirus, shows how to establish a ventilative and convectional PR environment to prevent the spread of virus through droplets, how to guide the patients to carry out PR, how to carry out respiratory muscle training, effective cough, expectoration, sneeze, general exercise, digestive function rehabilitation and psychological rehabilitation, and how to clean and disinfect the PR environment.",2020,"Yang, F.; Liu, N.; Wu, J. Y.; Hu, L. L.; Su, G. S.; Zheng, N. S.",Zhonghua Jie He He Hu Xi Za Zhi,3005028983,#252,
,CZI,Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia,10.3760/cma.j.issn.1001-0939.2020.0005,,32026671,,"Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients,serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased(15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mildgroup. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-α), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.",2020,"Chen, L.; Liu, H. G.; Liu, W.; Liu, J.; Liu, K.; Shang, J.; Deng, Y.; Wei, S.",Zhonghua Jie He He Hu Xi Za Zhi,3001118548,#473,
,CZI,Expert consensus for bronchoscopy during the epidemic of 2019 Novel Coronavirus infection (Trial version),10.3760/cma.j.issn.1001-0939.2020.0006,,32033514,,"Infection with 2019 Novel Coronavirus (2019-nCoV) is mainly transmitted by respiratory droplets, airborne transmission and direct contact. However, conducting bronchoscopy on patients with 2019-nCoV is a high-risk procedure in which health care workers are directly exposed to the virus, and the protection and operation procedures need to be strictly regulated. According to the characteristics of bronchoscopy, it is necessary to formulate the procedure, requirements and precautions when conducting bronchoscopy in the current epidemic situation. Relevant standards for preventing from infections should be strictly implemented in the operation of bronchoscopy. It needs to emphasize that bronchoscopy should not be used as a routine means for the diagnosis of 2019-nCoV infection sampling. The indications for bronchoscopy for other diseases should be strictly mastered, and it is suggested that bronchoscopy should be postponed for those patients who is not in urgent situation.",2020,"Group of Interventional Respiratory Medicine, Chinese Thoracic Society",Zhonghua Jie He He Hu Xi Za Zhi,3004450134,#481,
,CZI,Expert consensus on the use of corticosteroid in patients with 2019-nCoV pneumonia,10.3760/cma.j.issn.1001-0939.2020.0007,,32034899,,,2020,"Zhao, J. P.; Hu, Y.; Du, R. H.; Chen, Z. S.; Jin, Y.; Zhou, M.; Zhang, J.; Qu, J. M.; Cao, B.",Zhonghua Jie He He Hu Xi Za Zhi,2234990575,#480,
,CZI,Recommendations on extracorporeal life support for critically ill patients with novel coronavirus pneumonia,10.3760/cma.j.issn.1001-0939.2020.0009,,32035430,,"Along with the sharp increase of confirmed cases novel coronavirus infection, more critically ill cases require extracorporeal membrane oxygenation (ECMO) support. Based on the clinical data of novel coronavirus pneumonia (NCP), as well as the dada from previous clinical studies and the recommendations from the Extracorporeal Life Support Organization (ELSO), the committee board of the Chinese Society of Extracorporeal Life Support (CSECLS) made this recommendations to guide clinical ECMO application in the patients with NCP.",2020,"Chinese Society of Extracorporeal Life, Support",Zhonghua Jie He He Hu Xi Za Zhi,2930768960,#571,
,CZI,Respiratory support for severe 2019-nCoV pneumonia suffering from acute respiratory failure: time and strategy,10.3760/cma.j.issn.1001-0939.2020.0010,,32048501,,"Respiratory support is a very important technique for saving severe 2019-nCoV pneumonia patients who suffering respiratory failure, which can improve oxygenation, reduce mortality. Therefore, how to reasonable using respiratory support technique is the key point that relating success or failure. In this paper, the authors introduce their experience on treating severe 2019-nCoV pneumonia, it is hopeful for current fighting against 2019-nCoV in China.",2020,"Yuan, X.; Mu, J. S.; Mo, G. X.; Hu, X. S.; Yan, P.; Xie, L. X.",Zhonghua Jie He He Hu Xi Za Zhi,2878534291,#712,
,CZI,Pharmacotherapeutics for the New Coronavirus Pneumonia,10.3760/cma.j.issn.1001-0939.2020.0012,,32057209,,"The New Coronavirus Pneumonia (NCP, also named as COVID-19 by WHO on Feb 11 2020, is now causing a severe public health emergency in China since. The number of diagnosed cases is more than 40,000 until the submission of this manuscript. Coronavirus has caused several epidemic situations world widely, but the present contagious disease caused by 2019 new Coronavirus is unprecedentedly fulminating. The published cohorts of 2019 new Coronavirus (n-Cov) are single-center studies, or retrospective studies. We here share the therapeutic experiences of NCP treatment with literature review. Combination of Ribavirin and Interferon-α is recommended by the 5(th) edition National Health Commission's Regimen (Revised Edition) because of the effect on MERS (Middle East Respiratory Syndrome), and the effectiveness of Lopinavir/Ritonavir and Remdisivir needs to be confirmed by randomized controlled trial (RCT), given the situation of no specific antivirus drug on NCP is unavailable. Systemic glucocorticosteroid is recommended as a short term use (1~2 mg.kg(-1).d(-1), 3~5d ) by the 5(th) edition National Health Commission's Regimen (Revised Edition) yet RCTs are expected to confirm the effectiveness. Inappropriate application of antibiotics should be avoided, especially the combination of broad-spectrum antibiotics, for the NCP is not often complicated with bacterial infection.",2020,"Du, B.; Qiu, H. B.; Zhan, X.; Wang, Y. S.; Kang, H. Y. J.; Li, X. Y.; Wang, F.; Sun, B.; Tong, Z. H.",Zhonghua Jie He He Hu Xi Za Zhi,2780363919,#1150,
,CZI,Clinical features of 2019 novel coronavirus pneumonia in the early stage from a fever clinic in Beijing,10.3760/cma.j.issn.1001-0939.2020.0013,,32061066,,"Objective: To summarize and analyze the clinical and imaging characteristics of patients with 2019 novel coronavirus pneumonia in the early stage in Beijing. Methods: A retrospective analysis of clinical and imaging data of 9 patients with 2019 novel coronavirus infection diagnosed in one fever clinicic in Beijing from January 18, 2020 to February 3, 2020. Results: 5 male and 4 female was included in those 9 patients, whose median age was 36 years, and the age range from 15 to 49 years. 8 of these patients had no underlying disease and one suffered from diabetes. 7 patients had a history of travel to Wuhan City or Hubei Province, and one patient was a medical staff. Two family clustered was found. The incubation period was 1 to 6 days. The clinical manifestations were fever in 8 cases (8/9) , dry cough in 5 cases (5/9) , pharyngalgia in 4 cases (4/9) , fatigue in 4 cases (4/9) , body soreness in 4 cases (4/9) , and blocked or watery nose in 1 case (1/9) . Six patients (6/9) had abnormal cell peripheral blood, of which 3 (3/9) had an increased monocyte count, 2 (2/9) had a reduced lymphocyte , and 1 (1/9) had an increased leukocyte count, while the 3 patients had normal cell blood routines. The median of CRP was 16.3 mg/L, including 5 patients with slightly elevated (5/9) , 4 patients with normal values (4/9) . the results of procalcitonin test were negative in5 patients. Three patients were examined by chest X-ray examination, one of which was normal, one case showed infiltrates of right upper lung, and another showed in right lower lung. All patients underwent chest HRCT. And 7 cases (7/9) showed multiple ground glass exudation, including 5 cases (5/7) involved bilateral lungs, 2 cases (2/7) involved unilateral lung, 3 cases (3/7) with patchy consolidation, and 2 cases (2/9) showed no abnormality. Conclusions: The patents with 2019 novel coronavirus pneumonia in this study generally have an epidemiological history. The clinical manifestations are fever and cough. Peripheral white blood cell counts were most normal And PCT were all negative. Chest HRCT manifested as multiple ground-glass opacities with partly consolidation. Some patients had normal chest radiographs but HRCT showed pneumonia. Some patients had no pneumonia on chest HRCT.",2020,"Zhang, M. Q.; Wang, X. H.; Chen, Y. L.; Zhao, K. L.; Cai, Y. Q.; An, C. L.; Lin, M. G.; Mu, X. D.",Zhonghua Jie He He Hu Xi Za Zhi,3006640104,#891,
,CZI,Inhibitors of RAS Might Be a Good Choice for the Therapy of COVID-19 Pneumonia,10.3760/cma.j.issn.1001-0939.2020.0014,,32061198,,"The novel coronavirus 2019 (COVID-19) infected patients by binding human ACE2, leading to severe pneumonia and highly mortality rate in patients. At present, there is no definite and effective treatment for COVID-19. ACE2 plays an important role in the RAS, and the imbalance between ACE/Ang II/AT1R pathway and ACE2/Ang (1-7)/Mas receptor pathway in the RAS system will lead to multi-system inflammation. Increased ACE and Ang II are poor prognostic factors for severe pneumonia. Animal studies have shown that RAS inhibitors could effectively relieve symptoms of acute severe pneumonia and respiratory failure. The binding of COVID-19 and ACE2 resulted in the exhaustion of ACE2, and then ACE2/Ang (1-7)/Mas receptor pathway was inhibited. The balance of the RAS system was broken, and this would lead to the exacerbation of acute severe pneumonia. Therefore, we speculate that ACEI and AT1R inhibitors could be used in patients with COVID-19 pneumonia under the condition of controlling blood pressure, and might reduce the pulmonary inflammatory response and mortality.",2020,"Sun, M. L.; Yang, J. M.; Sun, Y. P.; Su, G. H.",Zhonghua Jie He He Hu Xi Za Zhi,3006039930,#912,
,CZI,Conventional respiratory support therapy for Severe Acute Respiratory Infections (SARI): Clinical indications and nosocomial infection prevention and control,10.3760/cma.j.issn.1001-0939.2020.0015,,32061199,,"Severe acute respiratory infection (SARI) diseases (such as SARS, MERS, pH1N1) can rapidly progress to acute respiratory failure with high lethality. The outbreak of a novel coronavirus infection can lead to 15% ~ 30% patients developing into acute respiratory distress syndrome (ARDS). Respiratory support is the most important therapy for SARI patients with respiratory failure. However, respiratory support is a high skilled technology, which means inappropriate application may bring related complications and cross infection of SARI pathogens among medical staff and non-medical personnel in hospital. Therefore, it is meaningful to established a standardized indication of respiratory support and to prevent related nosocomial transmission in SARI patients.",2020,"Critical care committee of Chinese Association of Chest, Physician; Respiratory; critical care group of Chinese Thoracic, Society; Respiratory care group of Chinese Thoracic, Society",Zhonghua Jie He He Hu Xi Za Zhi,2937860957,#985,
,CZI,Clinical characteristics of 30 medical workers infected with new coronavirus pneumonia,10.3760/cma.j.issn.1001-0939.2020.0016,,32062957,,"Objective: To investigate the clinical characteristics of medical staff with novel coronavirus pneumonia(NCP). Methods: 30 patients infected with novel coronavirus referred to jianghan university hospital between January 11, 2020 and January 3, 2020 were studied. The data reviewed included those of clinical manifestations, laboratory investigation and Radiographic features. Results: The patients consisted of 10 men and 20 women, including 22 doctors and 8 nurses,aged 21~59 years(mean 35±8 years).They were divided to 26 common type and 4 severe cases, all of whom had close(within 1m) contact with patients infected of novel coronavirus pneumonia. The average contact times were 12 (7,16) and the average cumulative contact time was 2 (1.5,2.7) h.Clinical symptoms of these patients were fever in 23 patients (76.67%) , headache in 16 petients (53.33%) , fatigue or myalgia in 21patients (70%) , nausea, vomiting or diarrhea in 9 petients (30%) , cough in 25 petients (83.33%) , and dyspnea in 14 petients (46.67%) .Routine blood test revealed WBC <4.0×10(9)/L in 8 petients (26.67%) , (4-10) ×10(9)/L in 22 petients (73.33%) , and WBC>4.0×10(9)/L in 4 petients (13.33%) during the disease.Lymphocyte count <1.0×10(9)/L occurred in 12 petients (40%),abnormal liver function in 7 petients (23.33%) ,myocardial damage in 5 petients(16.67%), elevated D-dimer (>0.5mg/l) in 5 patients (16.67%). Compared with normal patients, the average exposure times, cumulative exposure time, BMI, Fever time, white blood cell count, liver enzyme, LDH, myoenzyme and D-dimer were significantly increased in severe patients, while the lymphocyte count and albumin levels in peripheral blood were significantly decreased.Chest CT mainly showed patchy shadows and interstitial changes.According to imaging examination, 11 patients (36.67%) showed Unilateral pneumonia and 19 patients (63.33%) showed bilateral pneumonia,4 patients (13.33%) showed bilateral multiple mottling and ground-glass opacity.Compared with the patients infected in the protected period, the proportion of severe infection and bilateral pneumonia were both increased in the patients infected in unprotected period. Conclusion: Medical staffs are at higher risk of infection.Infection rates are associated with contact time, the amount of suction virus. Severe patients had BMI increased, heating time prolonged , white blood cell count, lymphocyte count, D-dimer and albumin level significantly changed and were prone to be complicated with liver damage and myocardial damage.Strict protection measures is important to prevent infection for medical workers.",2020,"Liu, M.; He, P.; Liu, H. G.; Wang, X. J.; Li, F. J.; Chen, S.; Lin, J.; Chen, P.; Liu, J. H.; Li, C. H.",Zhonghua Jie He He Hu Xi Za Zhi,3005079553,#1008,
,CZI,Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia,10.3760/cma.j.issn.1001-0939.2020.0019,,32075365,,"At the end of December 2019, a novel coronavirus (COVID-19) caused an outbreak in Wuhan, and has quickly spread to all provinces in China and 26 other countries around the world, leading to a serious situation for epidemic prevention. So far, there is still no specific medicine. Previous studies have shown that chloroquine phosphate (chloroquine) had a wide range of antiviral effects, including anti-coronavirus. Here we found that treating the patients diagnosed as novel coronavirus pneumonia with chloroquine might improve the success rate of treatment, shorten hospital stay and improve patient outcome. In order to guide and regulate the use of chloroquine in patients with novel coronavirus pneumonia, the multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia developed this expert consensus after extensive discussion. It recommended chloroquine phosphate tablet, 500mg twice per day for 10 days for patients diagnosed as mild, moderate and severe cases of novel coronavirus pneumonia and without contraindications to chloroquine.",2020,"multicenter collaboration group of Department of, Science; Technology of Guangdong, Province; Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus, pneumonia",Zhonghua Jie He He Hu Xi Za Zhi,3004896587,#1543,
,CZI,Expert consensus on preventing nosocomial transmission during respiratory care for critically ill patients infected by 2019 novel coronavirus pneumonia,10.3760/cma.j.issn.1001-0939.2020.0020,,32077661,,"Definite evidence has shown that the novel coronavirus (COVID-19) could be transmitted from person to person, so far more than 1,700 bedside clinicians have been infected. A lot of respiratory treatments for critically ill patients are deemed as high-risk factors for nosocomial transmission, such as intubation, manual ventilation by resuscitator, noninvasive ventilation, high-flow nasal cannula, bronchoscopy examination, suction and patient transportation, etc, due to its high possibility to cause or worsen the spread of the virus. As such, we developed this consensus recommendations on all those high-risk treatments, based on the current evidence as well as the resource limitation in some areas, with the aim to reduce the nosocomial transmission and optimize the treatment for the COVID-19 pneumonia patients. Those recommendations include: (1) Standard prevention and protection, and patient isolation; (2) Patient wearing mask during HFNC treatment; (3) Using dual limb ventilator with filters placed at the ventilator outlets, or using heat-moisture exchanger (HME) instead of heated humidification in single limb ventilator with HME placed between exhalation port and mask; avoid using mask with exhalation port on the mask; (4) Placing filter between resuscitator and mask or artificial airway; (5) For spontaneous breathing patients, placing mask for patients during bronchoscopy examination; for patients receiving noninvasive ventilation, using the special mask with bronchoscopy port to perform bronchoscopy; (6) Using sedation and paralytics during intubation, cuff pressure should be maintained between 25-30 cmH(2)O; (7) In-line suction catheter is recommended and it can be used for one week; (8) Dual-limb heated wire circuits are recommended and only changed with visible soiled; (9. For patients who need breathing support during transportation, placing an HME between ventilator and patient; (10) PSV is recommended for implementing spontaneous breathing trial (SBT), avoid using T-piece to do SBT. When tracheotomy patients are weaned from ventilator, HME should be used, avoid using T-piece or tracheostomy mask. (11) Avoid unnecessary bronchial hygiene therapy; (12) For patients who need aerosol therapy, dry powder inhaler metered dose inhaler with spacer is recommended for spontaneous breathing patients; while vibrating mesh nebulizer is recommended for ventilated patients and additional filter is recommended to be placed at the expiratory port of ventilation during nebulization.",2020,"Respiratory care committee of Chinese Thoracic, Society",Zhonghua Jie He He Hu Xi Za Zhi,2110407084,#1510,
,CZI,The prevention and control of a new coronavirus infection in department of stomatology,10.3760/cma.j.issn.1002-0098.2020.0001,,32057210,,"During a short period of time, the outbreak of pneumonia caused by a novel coronavirus, named Novel Coronavirus Pneumonia (NCP), was first reported in China, spreading to 24 countries and regions rapidly. The number of confirmed cases and deaths continued to rise. World Health Organization (WHO) announced that the outbreaks of the novel coronavirus have constituted a Public Health Emergency of International Concern. Efficient infection control can prevent the virus from further spreading, which makes the epidemic situation under control. Due to the specialty of oral healthcare settings, the risk of cross infection is severe among patients and oral healthcare practitioners. It's more urgent to implement strict and efficient infection control protocols. This paper, based on existing guidelines and published researches pertinent to dental infection-control principles and practices, mainly discusses epidemiological characteristics of NCP and the features of nosocomial infection in oral healthcare settings, and furthermore provides recommendations on patient's evaluation, and infection control protocols in department of stomatology under current circumstance..",2020,"Li, Z. Y.; Meng, L. Y.",Zhonghua Kou Qiang Yi Xue Za Zhi,2377782053,#1228,
,CZI,Management and clinical thinking of Coronavirus Disease 2019,10.3760/cma.j.issn.1007-3418.2020.0002,,32125126,,"In December 2019, the 2019 novel coronavirus pneumonia (NCP, officially named Coronavirus Disease 2019(COVID-19) by the World Health Organization) broke out in Wuhan, Hubei, and it quickly spread to the whole country and abroad. The situation was at stake. The sudden and serious COVID-19 epidemic has brought us a lot of urgent problems. How to effectively control the spread of COVID-19? When does the population infection rate rise to its peak? What will eventually be the number of infected patients? How to make early diagnosis? What effective antiviral drugs are available? How to effectively treat with existing drugs? Can it successfully improve the survival rate of critically patients? In response to the above questions, we put forward corresponding suggestions and reflections from the perspective of the infectious clinician.",2020,"Ma, K.; Chen, T.; Han, M. F.; Guo, W.; Ning, Q.",Zhonghua Gan Zang Bing Za Zhi,2895837418,#3337,
,CZI,Novel coronavirus pneumonia related liver injury: etiological analysis and treatment strategy,10.3760/cma.j.issn.1007-3418.2020.02.001,,32075364,,"The outbreak of novel coronavirus pneumonia(NCP) caused by 2019 novel coronavirus has become a global public health challenge. Some patients accompany with liver function damage in addition to the main typical respiratory symptom. Here we analyzed the clinical features, susceptible population, potential causes and therapeutic strategies of NCP related liver injury.",2020,"Hu, L. L.; Wang, W. J.; Zhu, Q. J.; Yang, L.",Zhonghua Gan Zang Bing Za Zhi,2076942479,#2261,
,CZI,Exploring the mechanism of liver enzyme abnormalities in patients with novel coronavirus-infected pneumonia,10.3760/cma.j.issn.1007-3418.2020.02.002,,32077659,,"Objective: To explore and analyze the possible mechanism of liver injury in patients with coronavirus disease 2019 (novel coronavirus pneumonia, NCP). Methods: The correlation between ALT, AST and other liver enzyme changes condition and NCP patients' disease status reported in the literature was comprehensively analyzed. ACE2 expression in liver tissue for novel coronavirus was analyzed based on single cell sequencing (GSE115469) data. RNA-Seq method was used to analyze Ace2 expression and transcription factors related to its expression in liver tissues at various time-points after hepatectomy in mouse model of acute liver injury with partial hepatectomy. t-test or Spearman rank correlation analysis was used for statistical analysis. Results: ALT and AST were abnormally elevated in some patients with novel coronavirus infection, and the rate and extent of ALT and AST elevation in severe NCP patients were higher than those in non-severe patients. Liver tissue results of single cell sequencing and immunohistochemistry showed that ACE2 was only expressed in bile duct epithelial cells of normal liver tissues, and very low in hepatocytes. In a mouse model of acute liver injury with partial hepatectomy, Ace2 expression was down-regulated on the first day, but it was elevated up to twice of the normal level on the third day, and returned to normal level on seventh day when the liver recovered and hepatocyte proliferation stopped. Whether this phenomenon suggests that the bile duct epithelial cells with positive expression of Ace2 participate in the process of liver regeneration after partial hepatectomy deserves further study. In RNA-Seq data, 77 transcription factors were positively correlated with the expression of ACE2 (r > 0.2, FDR < 0.05), which were mainly enriched in the development, differentiation, morphogenesis and cell proliferation of glandular epithelial cells. Conclusion: We assumed that in addition to the over activated inflammatory response in patients with NCP, the up-regulation of ACE2 expression in liver tissue caused by compensatory proliferation of hepatocytes derived from bile duct epithelial cells may also be the possible mechanism of liver tissue injury caused by 2019 novel coronavirus infection.",2020,"Guan, G. W.; Gao, L.; Wang, J. W.; Wen, X. J.; Mao, T. H.; Peng, S. W.; Zhang, T.; Chen, X. M.; Lu, F. M.",Zhonghua Gan Zang Bing Za Zhi,2006335368,#1637,
,CZI,Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study,10.3760/cma.j.issn.1007-3418.2020.02.003,,32077660,,"Objective: To analyze the clinical characteristics of cases of novel coronavirus pneumonia and a preliminary study to explore the relationship between different clinical classification and liver damage. Methods: Consecutively confirmed novel coronavirus infection cases admitted to seven designated hospitals during January 23, 2020 to February 8, 2020 were included. Clinical classification (mild, moderate, severe, and critical) was carried out according to the diagnosis and treatment program of novel coronavirus pneumonia (Trial Fifth Edition) issued by the National Health Commission. The research data were analyzed using SPSS19.0 statistical software. Quantitative data were expressed as median (interquartile range), and qualitative data were expressed as frequency and rate. Results: 32 confirmed cases that met the inclusion criteria were included. 28 cases were of mild or moderate type (87.50%), and four cases (12.50%) of severe or critical type. Four cases (12.5%) were combined with one underlying disease (bronchial asthma, coronary heart disease, malignant tumor, chronic kidney disease), and one case (3.13%) was simultaneously combined with high blood pressure and malignant tumor. The results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBil) for entire cohort were 26.98 (16.88 ~ 46.09) U/L and 24.75 (18.71 ~ 31.79) U/L, 39.00 (36.20 ~ 44.20) g/L and 16.40 (11.34- ~ 21.15) mmol/L, respectively. ALT, AST, ALB and TBil of the mild or moderate subgroups were 22.75 (16.31- ~ 37.25) U/L, 23.63 (18.71 ~ 26.50) U/L, 39.70 (36.50 ~ 46.10) g/L, and 15.95 (11.34 ~ 20.83) mmol/L, respectively. ALT, AST, ALB and TBil of the severe or critical subgroups were 60.25 (40.88 ~ 68.90) U/L, 37.00 (20.88 ~ 64.45) U/L, 35.75 (28.68 ~ 42.00) g/L, and 20.50 (11.28 ~ 25.00) mmol/L, respectively. Conclusion: The results of this multicenter retrospective study suggests that novel coronavirus pneumonia combined with liver damage is more likely to be caused by adverse drug reactions and systemic inflammation in severe patients receiving medical treatment. Therefore, liver function monitoring and evaluation should be strengthened during the treatment of such patients.",2020,"Liu, C.; Jiang, Z. C.; Shao, C. X.; Zhang, H. G.; Yue, H. M.; Chen, Z. H.; Ma, B. Y.; Liu, W. Y.; Huang, H. H.; Yang, J.; Wang, Y.; Liu, H. Y.; Xu, D.; Wang, J. T.; Yang, J. Y.; Pan, H. Q.; Zou, S. Q.; Li, F. J.; Lei, J. Q.; Li, X.; He, Q.; Gu, Y.; Qi, X. L.",Zhonghua Gan Zang Bing Za Zhi,2564157091,#1567,
,CZI,Treatment strategy for gastrointestinal tumor under the outbreak of novel coronavirus pneumonia in China,10.3760/cma.j.issn.1671-0274.2020.02.001,,32074786,,"The outbreak of the novel coronavirus pneumonia (NCP) has become a public health emergency in China. Chinese authorities and health agencies had devoted great efforts to control this disease. As surgeons specialized in the treatment of gastrointestinal tumors, we should always be aware of the prevention for NCP and incorporate this awareness into every detail of clinical practice. For the patients with gastrointestinal tumors, pre-admission screening should be done in order to rule out NCP. Real-time RT-PCR panel and chest CT scan should be conducted for patients with fever (>37.3℃), travel history to Hubei Province within 14 days, or contact history with residents from Wuhan district within 14 days. Prevention measures for both medical staffs and the screen-negative admitted patients should also be enhanced because false negative is possible. Medical instruments should be properly discarded or disinfected according to standardized procedures established by the local center for disease control and prevention (CDC). Surgical operation should be reduced at a minimal level to prevent cross infection in this special period.Surgical intervention for benign tumor should be postponed. For malignant tumor, multidisciplinary therapy (MDT) is recommended and non-surgical anti-tumor therapy should be selected with higher priority. Neoadjuvant therapy is highly recommended for gastrointestinal cancer at advanced stages that meet the indications of NCCN guideline (gastric cancer T stage ≥ 2/rectal cancer T stage ≥ 3/unresectable colon cancer). Gastric or esophagogastricjunction (EGJ) malignant tumor with obstruction can be managed with gastric tube decompression or stent placement to relieve the symptoms. Transnasal enteral feeding tube intubation/percutaneous endoscopic gastrostomy could be adopted to ensure enteral nutrition supply. For colorectal malignancy with simple intestinal obstruction, stent placement can achieve a high success rate, which not only helps avoid emergency surgery, but also creates a better condition for subsequent surgery. Transcatheter arterial embolization for hemostasis is an alternative choice for gastrointestinal tumor with bleeding. However, emergency operation still must be performed for patients with acute uncontrolled bleeding, obstruction or after other alternative treatment measures fail. All cases with suspicious or confirmed with NCP must be reported to the local CDC department. All invasive intervention must be performed in a designated isolation area. Tertiary prevention measure must be adopted for all anesthetists with additional face mask or medical goggle protection to prevent respiratory droplet transmission. Preventive enterostomy is preferable in lower digestive tract surgery. Thoroughly disinfecting the operating room after surgery is necessary. Fever after surgery must be carefully differentiated whether it's caused by post-surgery abdominal infection/inflammation or NCP. Single-room isolation and related examinations should be performed according to the standard procedures. We believe that with the unprecedentedly joint efforts of doctors and patients, we will eventually win this war against NCP.",2020,"Chen, Y. H.; Peng, J. S.",Zhonghua Wei Chang Wai Ke Za Zhi,2606110885,#2332,
,CZI,Several suggestion of operation for colorectal cancer under the outbreak of Corona Virus Disease 19 in China,10.3760/cma.j.issn.1671-0274.2020.03.002,,32074719,,"Pneumonia caused by SARS-Cov-2 infection has been reported in Wuhan since December 2019, and spread rapidly across the country. The radical operation of colorectal cancer is confine operation. Patients with colorectal cancer should receive operation as soon as possible after elective operation is resumed in each hospital. SARS-Cov-2 virus can be transmitted by asymptomatic infectors, and it has been confirmed to be transmitted by droplets and contact. However, fecal-oral transmission and aerosol transmission have not been excluded. Based onLaparoscopic colorectal operation experiences, the author suggests that the surgery strategy for colorectal cancer patients under the COVID-19 situation. Recommending laparoscopy-assisted radical surgery for colorectal cancer patients. The aerosols need to be strictly managed during operation. NOSES and TaTME should be carried out with cautious during the epidemic period. Protective stoma should be carried out scientifically and reasonably, and the protection of operating room personnel should be strengthened.",2020,"Yu, G. Y.; Lou, Z.; Zhang, W.",Zhonghua Wei Chang Wai Ke Za Zhi,2086544875,#1438,
,CZI,Suggestions for prevention of 2019 novel coronavirus infection in otolaryngology head and neck surgery medical staff,10.3760/cma.j.issn.1673-0860.2020.0001,,32023680,,"The epidemic of the 2019 Novel Coronavirus (2019-nCoV) infection has presented as a grim and complex situation recently. More than 11,000 cases of 2019-nCoV infection has been confirmed in China until February 1(st) 2020, which are causing great impact to economy and society, and seriously interfering with ordinary medical practice of otolaryngology and head and neck surgery. This advice guideline discusses the medical protection measures required in the outpatient clinic as well as in operation ward in otolaryngology head and neck department, which aims to protect medical staff from 2019-nCoV infection.",2020,"Xu, K.; Lai, X. Q.; Liu, Z.",Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi,3004896587,#254,
,CZI,Airway management of COVID-19 patients with severe pneumonia,10.3760/cma.j.issn.1673-0860.2020.04.001,,32100976,,"Patients with severe and critical COVID-19 will develop into acute respiratory distress syndrome in a short time. Noninvasive or invasive positive pressure ventilation will be important means for those patients, which will help to improve the clinical cure rate and reduce the mortality. Effective airway management has a great significance to improve respiratory support, reduce complications, and promote rehabilitation.",2020,,Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi,2974894063,#2471,
,CZI,Thinking on Clinical rational use of TCM injection in the treatment of novel coronavirus pneumonia (COVID-19),10.3760/cma.j.issn.cn112137-20200221-00388,,32122113,,,2020,"Wang, Z. F.; Wang, Y. P.; Zhang, H. M.; Fan, Y. P.; Lü, C.; Wang, Y. Y.",Zhonghua Yi Xue Za Zhi,1542898014,#3277,
,CZI,Cardiac manifestations of patients with COVID-19 pneumonia and related treatment recommendations,10.3760/cma.j.issn.cn112148-20200213-00077,,32118392,,引起2002年严重急性呼吸综合征（SARS）和2012年中东呼吸综合征（MERS）的冠状病毒(CoV)被证实是从动物传播至人类的。而2019新型 冠状病毒（2019-nCov）引起了新型冠状病毒肺炎的暴发，则再次证明CoV对人类健康具有重大的威胁。2019-nCov除感染呼吸系统外，研究报 道其对心血管系统也有侵害作用。本文对2019-nCov的基因组结构、功能以及感染者的病理生理学和心脏表型特征、心脏损伤的潜在机制、相关治疗策略进 行了梳理，警示临床医生注意2019-nCov对心脏的潜在风险、加强心脏功能管理。.,2020,"Tan, Z. C.; Fu, L. H.; Wang, D. D.; Hong, K.",Zhonghua xin xue guan bing za zhi,2999536665,#3988,
,CZI,Myocardial injury in patients with COVID-19 pneumonia,10.3760/cma.j.issn.cn112148-20200220-00106,,32118393,,自2019年12月以来，中国湖北省开始出现了2019新型冠状病毒（2019-nCoV）感染疫情并逐渐扩散至其他省份乃至其他国家。该病毒具有传播能 力强、临床表现多样、潜伏期长、可隐性传染等特征，对人类生命安全和健康造成严重威胁。随着病例数的不断增加和临床资料的不断丰富，2019-nCoV感 染患者除了典型的呼吸系统表现外，与病毒感染相关的心肌损伤情况逐渐受到重视。根据已公布的资料，我们总结了目前已知的2019-nCoV感染患者的心肌 损伤表现、特征、对病情及预后的影响，并对可能的损伤机制、治疗方法以及未来的研究方向作一论述。.,2020,"Wei, Z. Y.; Qian, H. Y.",Zhonghua xin xue guan bing za zhi,2365550483,#4193,
,CZI,Preliminary Recommendations for Lung Surgery during SARS-CoV-2 Novel Coronavirus Pneumonia Epidemic Period,10.3779/j.issn.1009-3419.2020.03.01,,32077440,,"In December 2019, China diagnosed the first patient with novel coronavirus pneumonia, and the following development of the epidemic had a huge impact on China and the whole world. For patients with lung occupying lesions, the whole process of diagnosis and treatment can not be carried out as usual due to the epidemic. For thoracic surgeons, the timing of surgical intervention should be very carefully considered. All thoracic surgeons in China should work together to develop the proper procedures for the diagnosis and treatment in this special situation, and continuously update the recommendations based on epidemic changes and further understanding of new coronavirus pneumonia. Here, we only offer some preliminary suggestions based on our own knowledge for further reference and discussion.",2020,"Li, Xin; Liu, Minghui; Zhao, Qingchun; Liu, Renwang; Zhang, Hongbing; Dong, Ming; Xu, Song; Zhao, Honglin; Wei, Sen; Song, Zuoqing; Chen, Gang; Chen, Jun",Zhongguo Fei Ai Za Zhi,3005538648,#1583,
,CZI,Clinical Management of Lung Cancer Patients during the Outbreak of 2019 Novel Coronavirus Disease (COVID-19),10.3779/j.issn.1009-3419.2020.03.02,,32077441,,"Since late December 2019, an outbreak of 2019 novel coronavirus diseases (COVID-19) in Wuhan, China has spread quickly nationwide. With the spread of COVID-19, the routine clinical diagnosis and treatment for lung cancer patients has been disturbed. Due to the systemic immunosuppressive of lung cancer patients caused by the malignancy and anticancer treatments, lung cancer patients are more susceptible to infection than healthy individuals. Furthermore, patients with cancer had poorer prognosis from infection. Lung cancer patients should be the priority group for COVID-19 prevention. The protection provisions and control measures aiming to protect lung cancer patients from COVID-19 have been increasingly concerned. During the COVID-19 outbreak period, it should be carefully differentiated for fever and respiratory symptoms for lung cancer patients receiving anti-tumor treatment, in order to evaluate the risk of COVID-19. Moreover, it is necessary to carry out meticulous and individualized clinical management for lung cancer patients to effectively protect the patients from COVID-19.",2020,"Xu, Yan; Liu, Hongsheng; Hu, Ke; Wang, Mengzhao",Zhongguo Fei Ai Za Zhi,2907814135,#1445,
,CZI,A Chinese Case of COVID-19 Did Not Show Infectivity During the Incubation Period: Based on an Epidemiological Survey,10.3961/jpmph.20.048,,32114755,,Controversy remains over whether the novel coronavirus 2019 (COVID-19) virus may have infectivity during the incubation period before the onset of symptoms. The author had the opportunity to examine the infectivity of COVID-19 during the incubation period by conducting an epidemiological survey on a confirmed patient who had visited Jeju Island during the incubation period. The epidemiological findings support the claim that the COVID-19 virus does not have infectivity during the incubation period.,2020,"Bae, Jong-Myon",J Prev Med Public Health,2029228287,#3073,
,CZI,Small Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Fusion by Targeting Cavities on Heptad Repeat Trimers,10.4062/biomolther.2019.202,,32126736,,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a newly emerging viral disease with fatal outcomes. However, no MERS-CoV-specific treatment is commercially available. Given the absence of previous structure-based drug discovery studies targeting MERS-CoV fusion proteins, this set of compounds is considered the first generation of MERS-CoV small molecule fusion inhibitors. After a virtual screening campaign of 1.56 million compounds followed by cell-cell fusion assay and MERS-CoV plaques inhibition assay, three new compounds were identified. Compound numbers 22, 73, and 74 showed IC(50) values of 12.6, 21.8, and 11.12 µM, respectively, and were most effective at the onset of spike-receptor interactions. The compounds exhibited safe profiles against Human embryonic kidney cells 293 (HEK293) at a concentration of 20 µM with no observed toxicity in Vero cells at 10 µM. The experimental results are accompanied with predicted favorable pharmacokinetic descriptors and drug-likeness parameters. In conclusion, this study provides the first generation of MERS-CoV fusion inhibitors with potencies in the low micromolar range.",2020,"Kandeel, Mahmoud; Yamamoto, Mizuki; Al-Taher, Abdulla; Watanabe, Aya; Oh-Hashi, Kentaro; Park, Byoung Kwon; Kwon, Hyung-Joo; Inoue, Jun-Ichiro; Al-Nazawi, Mohammed",Biomol Ther (Seoul),2139603860,#4352,
,CZI,Emergent Strategies for the Next Phase of COVID-19,10.4088/JCP.08m04485blu,,32100487,,,2020,"Huh, Kyungmin; Shin, Hyoung Shik; Peck, Kyong Ran",Infect Chemother,2071972290,#2255,
,CZI,Imported cases of 2019-novel coronavirus (2019-nCoV) infections in Thailand: Mathematical modelling of the outbreak,10.4103/1995-7645.277516,,,,"Imported cases of 2019-novel coronavirus (2019-nCoV) infections in Thailand: Mathematical modelling of the outbreak' in DOAJ. DOAJ is an online directory that indexes and provides access to quality open access, peer-reviewed journals.",2020,"Wiwanitkit, Pathum Sookaromdee; Viroj",Asian Pacific Journal of Tropical Medicine,3005391564,#2516,
,CZI,Emerging and re-emerging human infectious diseases: A systematic review of the role of wild animals with a focus on public health impact,10.4103/1995-7645.277535,,,,"Infectious diseases continue to impose unpredictable burdens on global health and economies, a subject that requires constant research and updates. In this sense, the objective of the present article was to review studies on the role of wild animals as reservoirs and/or dispersers of etiological agents of human infectious diseases in order to compile data on the main wild animals and etiological agents involved in zoonotic outbreaks. A systematic review was carried out using PRISMA guidelines, using the PubMed, Scopus and SciELO platforms as data banks. The descriptors used were “zoonosis”, “human infectious diseases” and “wild animals”. The results show that wild animals (mainly bats, birds and primates) play an important role in the dissemination of etiological agents (mainly viruses, as a new coronavirus called 2019 Novel Coronavirus) in extensive geographic regions. Moreover, these wild animal organisms can act as the site for essential biotic synergy among several pathogenic microorganisms, promoting a higher rate of adaptation, mutation and even genetic recombination, with consequent stimulation of new strains and subtypes, inducing new infectious agents with unknown virulent potential. In conclusion, the monitoring of these diseases and adequate preparation for possible epidemics and pandemics are fundamental conditions for the mitigation of their future impact. The zoonotic threat of these etiological agents and the impact on public health can be enormous as shown by the ongoing epidemic of 2019 novel coronavirus (2019- nCoV) infections.",2020,"Siqueira-Batista, Marli C. Cupertino; Michely, B. Resende; Nicholas, A. J. Mayer; Lorendane, M. Carvalho; Rodrigo",Asian Pacific Journal of Tropical Medicine,3004810054,#2543,
,CZI,Novel coronavirus (2019-nCoV) update: What we know and what is unknown,10.4103/1995-7645.277795,,,,"Preliminary clinical features indicated that most of the infected patients were men with underlying diseases (comorbidities) including diabetes, hypertension, cardiovascular disease, chronic obstructive pulmonary disease, malignancy and chronic liver disease[6]. Patient presented with fever, cough, myalgia, sputum production, headache, haemoptysis, diarrhea and dyspnea[6]. Person- to-person transmission and familiar association have also been confirmed[7]. To date, a diagnostic kit has been developed for 2019- nCoV[8], and efforts are ongoing to develop other protocols. Whilst several important aspects of 2019-nCoV epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, have been defined, there remain many unanswered questions, including source, transmission and epidemic potential. The Wuhan outbreak is a stark reminder of the continuing threat of zoonotic diseases.",2020,"Fasina, Folorunso Oludayo",Asian Pacific Journal of Tropical Medicine,3004467862,#2646,
,CZI,Dose prediction of lopinavir/ritonavir for 2019-novel coronavirus (2019-nCoV) infection based on mathematic modeling,10.4103/1995-7645.277815,,,,"At present, lopinavir/ritonavir is widely used for possible treatment of 2019-nCoV infection in countries that the emerging infection exists. Here, the authors used a mathematical modelling theoretical approach to predict the expectedproper dosage of lopinavir/ritonavir for possible treatment of 2019-nCoV infection. The protocol for mathematical modeling in this work is the same as previous report by Wiwanitkit et al[5]. Briefly, the primary agreement was there had to be a specific amount of required energy for reaction between lopinavir/ritonavir and its target enzyme and this energy is a specific constant for the reaction. Based on bonding theory, the required amount of lopinavir/ritonavir was varied to the two substrates, lopinavir/ritonavir and target, protease. Here, the simple equation ‘A + B ? C where A was the target enzyme, B was lopinavir/ritonavir and C was end product’ could be written.",2020,"Wiwanitkit, Sora Yasri; Viroj",Asian Pacific Journal of Tropical Medicine,3006177842,#2515,
,CZI,Epidemiologic characteristics of early cases with 2019 novel coronavirus (2019-nCoV) disease in Republic of Korea,10.4178/epih.e2020007,,32035431,,"Since the first case of 2019 novel coronavirus (2019-nCoV) in South Korea was confirmed on January 20, 2020, there have been 24 confirmed cases of 2019-nCoV. The majority of these cases (58.3%; n=14) were male, with a median age of 42 years (range, 21-62 years). Of the confirmed cases, 15 were index cases (63%), six were first-generation patients (24%), and three were second-generation patients (12.5%). All the first- and second-generation patients were family members or close acquaintances of index cases. All the index cases entered the South Korea from January 19 to 24, 2020. The average incubation period was 3.6 days (median, 4 days) and the reproduction number (R0) was calculated as 0.5. Two of the confirmed cases were asymptomatic. As of February 8, 22 patients with 2019-nCoV are hospitalized in South Korea, and 2 have been discharged from the hospital. The epidemiological indicators will be revised as new information becomes available in the future. Sharing epidemiological information among researchers around the world is essential for efficient preparations and responses to new infectious diseases.",2020,"Ki, Moran; nCoV, Task Force For",Epidemiol Health,3006364226,#567,
,CZI,Understanding COVID-19 new diagnostic guidelines - a message of reassurance from an internal medicine doctor in Shanghai,10.4414/smw.2020.20216,,32134111,,,2020,"Bischof, E.; Chen, G.; Ferretti, M. T.",Swiss medical weekly,2073887351,#5063,
,CZI,Drug treatment options for the 2019-new coronavirus (2019-nCoV),10.5582/bst.2020.01020,,,,,2020,"Lu, Hongzhou","BioScience TrendsAB - As of January 22, 2020, a total of 571 cases of the 2019-new coronavirus (2019-nCoV) have been reported in 25 provinces (districts and cities) in China. At present, there is no vaccine or antiviral treatment for human and animal coro",3003322996,#55,
,CZI,Efficacies of lopinavir/ritonavir and abidol in the treatment of novel coronavirus pneumonia,10.5582/bst.2020.01030,,,,"Objective To evaluate the efficacies of lopinavir/ritonavir and abidol in the treatment of NCP. Methods The clinical data of 134 patients with NCP receiving treatment at Shanghai Public Health Clinical Center during Jan 20 to Feb 6, 2020 were retrospectively collected. All the patients received interferon-&alpha;2b spray and symptomatic supportive treatment, and 52 cases received oral lopinavir/ritonavir treatment, 34 cases received oral abidol treatment, the remaining 48 cases did not take any antiviral drugs. The efficacies at median day 7 among the three groups were compared by using Kruskal-Wallis or chi-square tests. Results The 134 patients included 69 males (51.5%) and 65 females, aged 35-62 years with the average of 48 years. The median time to temperature normalization in patients receiving abidol or lopinavir/ritonavir treatment was both 6 days after admission, and that was 4 days in the control group, with no significant difference ( &chi; 2 = 2.37, P =0.31). The median time to PCR negative in the respiratory specimens in the three groups was all 7 days after admission, and the PCR negative rates at day 7 after admission in lopinavir/ritonavir, abidol and control groups were 71.8% (28/39), 82.6% (19/23) and 77.1% (27/35), respectively, which were not significantly different ( &chi; 2 = 0.46 , P =0.79). Radiological worsening at day 7 was observed in comparable proportions of patients in the three groups, which were 42.3% ( n =22), 35.3% ( n =12) and 52.1% ( n =25), respectively ( &chi; 2 = 2.38, P =0.30) . Adverse reactions occurred in 17.3% ( n =9), 8.8% ( n =3) and 8.3% ( n =4) patients, respectively in the three groups ( &chi; 2 = 2.33, P =0.33). Conclusions This study did not find any effects of lopinavir/ritonavir and abidol on relieving symptoms or accelerating virus clearance. The efficacies of these two drugs in NCP treatment need further investigation.",2020,"CHEN, Jun; LING, Yun; XI, Xiuhong; LIU, Ping; LI, Feng; LI, Tao; SHANG, Zhiyin; WANG, Mei; SHEN, Yinzhong; LU, Hongzhou",Chinese Journal of Infectious Diseases,3004517278,#2339,
,CZI,Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment,10.5582/bst.2020.01030,,,,,2020,"Wang, Zhenwei; Chen, Xiaorong; Lu, Yunfei; Chen, Feifei; Zhang, Wei",BioScience Trends,3004517278,#549,
,CZI,Challenges to the system of reserve medical supplies for public health emergencies: reflections on the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in China,10.5582/bst.2020.01043,,32062645,,"On December 31, 2019, the Wuhan Municipal Health Commission announced an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), China is now at a critical period in the control of the epidemic. The Chinese Government has been taking a series of rapid, comprehensive, and effective prevention and control measures. As the pandemic has developed, a fact has become apparent: there is a serious dearth of emergency medical supplies, and especially an extreme shortage of personal protective equipment such as masks and medical protective clothing. This is one of the major factors affecting the progress of epidemic prevention and control. Although China has made great efforts to strengthen the ability to quickly respond to public health emergencies since the SARS outbreak in 2003 and it has clarified requirements for emergency supplies through legislation, the emergency reserve supplies program has not been effectively implemented, and there are also deficiencies in the types, quantity, and availability of emergency medical supplies. A sound system of emergency reserve supplies is crucial to the management of public health emergencies. Based on international experiences with pandemic control, the world should emphasize improving the system of emergency reserve medical supplies in the process of establishing and improving public health emergency response systems, and it should promote the establishment of international cooperative programs to jointly deal with public health emergencies of international concern in the future.",2020,"Wang, Xu; Zhang, Xiaoxi; He, Jiangjiang",Biosci Trends,3006332573,#1005,
,CZI,Recommendations on the pediatric flexible bronchoscopy during the outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in China (Trial Edition),10.5582/bst.2020.01043,,,,"An outbreak of pneumonia caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)infection has spread to children.Due to its strong infectivity, people are generally susceptible, including children.The main source of infection is the SARS-CoV-2 infection patients, asymptomatic infection may also become the source of infection. Bronchoscopy is a high-risk operation since during the procedure, with children & prime's coughing and an open airway, a huge number of droplets and secretions are produced, which will contaminate the desktop, equipment and air, and even infect medical staff, other children and caregivers in close contact.For this reason, experts were specially organized to write recommendations on the diagnosis and treatment of pediatric flexible bronchoscopy during the epidemic period of SARS-CoV-2 infection (trial version), establish indications and prevention and control plans of pediatric bronchoscopy during the epidemic period, and provide a basis for medical staff engaged in pediatric bronchoscopy.",2020,,Chinese Journal of Applied Clinical Pediatrics,3006332573,#1876,
,CZI,Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies,10.5582/bst.2020.01047,,,,,2020,"Gao, Jianjun; Tian, Zhenxue; Yang, Xu",BioScience Trends,2767584895,#1246,
,CZI,COVID-19: Real-time dissemination of scientific information to fight a public health emergency of international concern,10.5582/bst.2020.01056,,32092748,,"Rapidly sharing scientific information is an effective way to reduce public panic about COVID-19, and doing so is the key to providing real-time guidance to epidemiologists working to contain the outbreak, clinicians managing patients, and modelers helping to understand future developments and the possible effectiveness of various interventions. This issue has rapidly reviewed and published articles describing COVID-19, including the drug treatment options for SARS-CoV-2, its clinical characteristics, and therapies involving a combination of Chinese and Western medicine, the efficacy of chloroquine phosphate in the treatment of COVID-19 associated pneumonia according to clinical studies, and reflections on the system of reserve medical supplies for public health emergencies. As an academic journal, we will continue to quickly and transparently share data with frontline healthcare workers who need to know the epidemiological and clinical features of COVID-19.",2020,"Song, Peipei; Karako, Takashi",Biosci Trends,1559091631,#1766,
,CZI,Discovering drugs to treat coronavirus disease 2019 (COVID-19),10.5582/ddt.2020.01012,,,,"The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.",2020,"Dong, Liying; Hu, Shasha; Gao, Jianjun",Drug Discoveries & Therapeutics,2604381070,#5186,
,CZI,An outbreak of <scp>COVID</scp> ‐19 caused by a new coronavirus: what we know so far,10.5694/mja2.50530,,,,"An outbreak of a novel coronavirus, now formally named severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and causing coronavirus disease 2019 (COVID‐19), emerged in the city of Wuhan in Hubei province in central China in December 2019. The first cases were noted as a cluster of patients with pneumonia who were all linked to a live animal market, and testing found the presence of a previously unknown coronavirus. Coronaviruses are a group of viruses that affect both animals and humans, and several (OC43, 229E, HKU1 and NL63) are a cause of the common cold.1, 2 However, two coronaviruses have previously caused significant outbreaks associated with more severe disease: the SARS coronavirus in 2002–2003 and the Middle East respiratory syndrome coronavirus that emerged in 2012.1, 2 Chinese authorities and researchers should be commended for their rapid sharing of viral sequences which enabled laboratories worldwide to develop diagnostic tests within weeks of discovery of the pathogen.3 An Australian laboratory subsequently isolated the virus from a clinical sample (the first to do so outside of China), and rapidly shared this virus with relevant global agencies, further aiding diagnostic, therapeutic and vaccine development efforts. Information on the new virus and its impact is being updated constantly. We know that SARS‐CoV‐2 can cause severe disease, although active surveillance of contacts is required to define the milder end of the disease spectrum and to estimate the true hospitalisation and case fatality ratio. The cases reported to date suggest that most are older adults; it is currently unclear whether comorbidities reflect the age group affected or whether they are risk factors for severe disease.4, 5 Early studies using data before the institution of public health interventions in China suggest that SARS‐CoV‐2 is as transmissible as SARS coronavirus and probably more transmissible than influenza viruses.6, 7 The timing of infectiousness relative to symptom onset is a particularly important parameter with implications for public health control. While reports suggest that asymptomatic infection and transmission may result from minimally symptomatic cases, the contribution of this to transmission is not yet known.8 Careful analysis of early data suggests that the mean incubation period is 6 days, with a range of up to 14 days.9 Reports of large outbreaks, particularly associated with hospitals and closed communities, raise the possibility of “superspreading” events, a feature of previous coronavirus outbreaks.10 The importance of infection control is also reinforced by a report that 41% of cases in Wuhan were acquired nosocomially (including 40 health care workers and 17 patients).4 As at 26 February 2020, there were 23 confirmed cases of COVID‐19 in Australia, across five jurisdictions. Although reported case numbers in China are slowing, large outbreaks on a cruise ship in Japan, and in South Korea, Iran and Italy are concerning and highlight our interconnected world. However, it is likely that this will change in the days or weeks ahead. Although absolute case numbers are small in Australia, the public health, political and societal ramifications have already been considerable, ranging from travel restrictions on non‐Australians coming from China, the use of offshore and remote quarantine facilities, and disturbing reports of racism against members of our Asian community (https://insig​htplus.mja.com.au/2020/5/coron​avirus-no-place-for-racism-xenop​hobia/).",2020,"Cheng, Allen C.; Williamson, Deborah A.",Medical Journal of Australia,,#5128,
,CZI,"Reporting, Epidemic Growth, and Reproduction Numbers for the 2019 Novel Coronavirus (2019-nCoV) Epidemic",10.7326/M20-0358,,32023340,,,2020,"Tuite, Ashleigh R.; Fisman, David N.",Ann Intern Med,3004479334,#268,
,CZI,Disease control of 2019-novel coronavirus infection in hospital: West China urgent recommendation,10.7507/1672-2531.202001121,,,,"China is facing the serious situation of 2019-novel coronavirus (2019-nCoV) infection. The health care institutions have actively participated in the prevention, diagnosis, and treatment of the disease. Proper regulation of in-hospital policy may help control virus spreading. We developed seven key clinical questions about the prevention and control of 2019-novel coronavirus infection in a hospital, and provided recommendations based on the best available evidence and expert experience. We interpret the recommendations for better feasibility in Chinese hospital. We hope to provide evidence and reference for the domestic medical institutions to reasonably adjust the hospital workflow during 2019-nCoV infection period.",2020,"Li, S.; Huang, W.; Liao, X.; Li, D.; Du, L.; Song, J.; Zhou, Y.; Zhao, S.; Wang, Y.; Cao, X.; Wang, J.; Liu, J.; Zhu, S.; Li, L.; Hao, Q.; Zong, Z.; Sun, X.; Li, W.",Chinese Journal of Evidence-Based Medicine,3005477624,#3359,
,CZI,2019-novel coronavirus infection in a three-month-old baby,10.7759/cureus.4949,,,,,2020,"Zhang, Yuehua; Lin, Zhang; Xiao, Meifang; Wang, Jiachong; Wei, Yong; Lei, Zhixian; Zeng, Zhenqiong; Li, Ling; Li, Hongai; Xiang, Wei",Chinese Journal of Pediatrics,2951323607,#699,
,CZI,What we know so far: COVID-19 current clinical knowledge and research,10.7861/clinmed.2019-coron,,32139372,,"In December 2019, health authorities in Wuhan, China, identified a cluster of pneumonia cases of unknown aetiology linked to the city's South China Seafood Market. Subsequent investigations revealed a novel coronavirus, SARS-CoV-2, as the causative agent now at the heart of a major outbreak. The rising case numbers have been accompanied by unprecedented public health action, including the wholesale isolation of Wuhan. Alongside this has been a robust scientific response, including early publication of the pathogen genome, and rapid development of highly specific diagnostics. This article will review the new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease, and summarise its clinical features.",2020,"Lake, M. A.","Clinical medicine (London, England)",2775275772,#4794,
,CZI,Development of Genetic Diagnostic Methods for Novel Coronavirus 2019 (nCoV-2019) in Japan,10.7883/yoken.JJID.2020.061,,,,"At the end of 2019, pneumonia caused by novel coronavirus 2019 (nCoV) emerged in Wuhan city, China. Many airline travelers moved between Wuhan and Japan at that time, suggesting that Japan is at high risk of invasion by the virus. Diagnostic systems for 2019-nCoV were developed with urgency. Two nested RT-PCR assays and two real-time RT-PCR assays were adapted to local Japanese conditions. As of 8 February 2020, the assays developed have successfully detected 25 positive cases of infection in Japan.",2020,"Shirato, Kazuya; Nao, Naganori; Katano, Harutaka; Takayama, Ikuyo; Saito, Shinji; Kato, Fumihiro; Katoh, Hiroshi; Sakata, Masafumi; Nakatsu, Yuichiro; Mori, Yoshio; Kageyama, Tsutomu; Matsuyama, Shutoku; Takeda, Makoto",Japanese Journal of Infectious Diseases,3003886061,#5227,
,CZI,Finding an Accurate Early Forecasting Model from Small Dataset: A Case of 2019-nCoV Novel Coronavirus Outbreak,10.9781/ijimai.2020.02.002,,,,"Epidemic is a rapid and wide spread of infectious disease threatening many lives and economy damages. It is important to fore-tell the epidemic lifetime so to decide on timely and remedic actions. These measures include closing borders, schools, suspending community services and commuters. Resuming such curfews depends on the momentum of the outbreak and its rate of decay. Being able to accurately forecast the fate of an epidemic is an extremely important but difficult task. Due to limited knowledge of the novel disease, the high uncertainty involved and the complex societal-political factors that influence the widespread of the new virus, any forecast is anything but reliable. Another factor is the insufficient amount of available data. Data samples are often scarce when an epidemic just started. With only few training samples on hand, finding a forecasting model which offers forecast at the best efforts is a big challenge in machine learning. In the past, three popular methods have been proposed, they include 1) augmenting the existing little data, 2) using a panel selection to pick the best forecasting model from several models, and 3) fine-tuning the parameters of an individual forecasting model for the highest possible accuracy. In this paper, a methodology that embraces these three virtues of data mining from a small dataset is proposed. An experiment that is based on the recent coronavirus outbreak originated from Wuhan is conducted by applying this methodology. It is shown that an optimized forecasting model that is constructed from a new algorithm, namely polynomial neural network with corrective feedback (PNN+cf) is able to make a forecast that has relatively the lowest prediction error. The results showcase that the newly proposed methodology and PNN+cf are useful in generating acceptable forecast upon the critical time of disease outbreak when the samples are far from abundant.",2020,"Fong, Simon James; Li, Gloria; Dey, Nilanjan; Gonzalez-Crespo, Rubén; Herrera-Viedma, Enrique",International Journal of Interactive Multimedia and Artificial Intelligence,3004754245,#3177,
,CZI,Coronavirus : rester proactif,,,32022502,,,2020,"Gardier, Stéphany; Petignat, Christiane",Rev Med Suisse,,#323,
,CZI,2019-nCoV : leçons d’incertitudes et de mondialisation,,,32049463,,,2020,"Matter, Michel",Rev Med Suisse,,#750,
,CZI,The possibility of using Lopinave/Litonawe (LPV/r) as treatment for novel coronavirus （2019-nCov）pneumonia: a quick systematic review based on earlier coronavirus clinical studies,,,,,"&lt;p&gt;&lt;b&gt;Objective&lt;/b&gt;To explore the possibility of using Lopinave/Litonawe (LPV/r) as treatment for novel coronavirus 2019-nCov pneumonia by systematically review earlier coronavirus studies.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods &lt;/b&gt;Systematically retrieve relevant clinical studies from Chinese and English databases such as CNKI,VIP,Wangfang Data,CBM,PubMed, Web of Science,EMBASE. In addition, information from Chinese biomedical journals, WHO, US CDC, Chinese CDC websites and the references from published relevant articles were retrieved. The inclusion period is from January 2003 to January 24, 2020. The criteria for inclusion are:(1) studies that aim to compare LPV/r and placebo/standard for SARS, MERS; (2) studies that include at least one clinical outcome; (3) studies with diagnosis criteria meeting WHO requirement on SARS or MERS; (4)data from multiple reports but originated from one study, where we extract information from all reports; (5)guidelines, includes: national or academic guidelines/experts &lsquo;consensus. The exclude criteria are: 1) only have abstracts but no full information; 2) in vitro studies. Two reviewers independently review articles and extract data on study design, patients, diagnosis criteria, regimen, and clinical outcomes (mortality, morbidity, quality of life, steroids dosage, chest image and adverse responses). &lt;/p&gt;&lt;p&gt;&lt;b&gt;Results&lt;/b&gt;Two hundred and thirty potential article were found by screening, and narrow down to forty-four articles for evaluation and fnally four studies were included. The results of included studies indicate the early use of LPV/r regimen can reduce the mortality of SARS and MERS, and reduce steroids dosing. &lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions&lt;/b&gt;ILPV/r can be used as a component of experimental regimen for treat 2019-nCoV pneumonia. It strongly suggests that initiating real world studies to explore the true clinical effects of LPV/r on 2019-nCoV patients.&lt;/p&gt;",2020,"Jiang, Hua; Deng, Hongfei; Wang, YU; Liu, Zhan; Sun, Mingwei; Zhou, Ping; Xia, Qi; Lu, Charles Damien; Zeng, Jun",Chinese Journal of Emergency Medicine,,#1050,
,CZI,Novo Coronavírus (2019-nCoV): nota técnica,,,,,"A Secretaria da Saúde do Estado do Ceará (SESA), através da Célula de Imunização (CEMUN) e o Centro de Informações Estratégicas em Vigilância em Saúde (CIEVS), da Coordenadoria de Vigilância Epidemiológica e Prevenção em Saúde (COVEP), vem por meio desta ALERTAR para a ocorrência de casos do Novo Coronavírus (2019-nCoV) no mundo.Essa nota deve ser divulgada amplamente entre profissionais de saúde de estabelecimentos públicos e privados",2020,"Ceará. Secretaria de, Saúde",,,#1860,
,CZI,Infecciones por Coronavirus. Diagnóstico y Tratamiento,,,,,"Boletín bibliográfico Bibliomed Suplemento ofrece en su edición especial de enero de 2020, una actualización sobre &quot;Infecciones por Coronavirus. Diagnóstico yTratamiento&quot;",2020,"Cuba. Centro Nacional de Información de Ciencias Médicas. Biblioteca Médica, Nacional",Boletín bibliográfico de la Biblioteca Médica Nacional,,#1852,
,CZI,"Initial Public Health Response and Interim Clinical Guidance for the 2019 Novel Coronavirus Outbreak — United States, December 31, 2019–February 4, 2020 | MMWR",,,,,"CDC, multiple other federal agencies, state and local health departments, and other partners are implementing aggressive measures to slow transmission of 2019-nCoV in the United States, be ready if widespread transmission occurs, and work on medical countermeasures.",2020,@CDCgov,,,#348,
,CZI,COVID-19 Update – March 2020 | Global Health | JN Learning | JAMA Ed Hub [Video recording],,,,,"Coronavirus testing, mortality, vaccine development, containment vs mitigation, and more. Anthony S. Fauci, MD discusses the latest developments in the global spread of COVID-19 and the SARS-CoV-2 virus with JAMA Editor Howard Bauchner, MD. - What's the difference between COVID-19 and SARS-CoV-2? (01:15) - What's the status and accuracy of diagnostic testing in the US? (01:58) - What's the case-fatality rate for the virus? (05:31) - Scientific advances and vaccine development (25:06) - Are current clinical trials providing a picture of treatments? (13:41) - Risk communication: how do we present information so there's faith that it's accurate? (15:24) - Risk groups (children, the elderly, pregnant women) (16:26) - Containment vs mitigation vs quarantine vs isolation (19:10) - Protecting the elderly and nursing home resident (23:52) - Public health prospects in Latin America, Africa (26:35) - Will coronavirus wane in warmer months like influenza? (27:52) - Why is anxiety so high about this disease?- Does the US have capacity to care for COVID19 infection? (31:03) - What is your daily schedule like? (32:23)",2020,JAMA,,,#4744,
,CZI,"Circular externa No 0000005 de 2020: Directrices para la detección temprana, el control y la atención ante la posible introducción del nuevo coronavirus (2019-nCoV) y la implementación de los planes de preparación y respuesta ante este riesgo",,,,,"El Ministerio de Salud y Protección Social y el Instituto Nacional de Salud, en ejercicio de las facultades señaladas en los Decretos 4107 y 4109, ambos de 2.011, y en el marco del Reglamento Sanitario Internacional -RSI-2005, y ante la situación epidemiológica por el nuevo coronavirus (2019-nCoV), declarada como emergencia en salud pública de importancia internacional (ESPII) por la Organización Mundial de la Salud (OMS) el día 30 de enero del año en curso: imparten instrucciones sobre las acciones que los destinatarios de esta circular deben observar para la vigilancia activa, preparación y toma de medidas de contención para una eventual introducción del virus en el territorio nacional. The Ministry of Health and Social Protection and the National Institute of Health, in exercise of the powers indicated in Decrees 4107 and 4109, both of 2,011, and within the framework of the International Health Regulations -RSI-2005, and before the epidemiological situation by the new coronavirus (2019-nCoV), declared as an emergency in public health of international importance (ESPII) by the World Health Organization (WHO) on January 30 of this year: they give instructions on the actions that the recipients of This circular must observe for the active surveillance, preparation and taking of containment measures for an eventual introduction of the virus into the national territory.",2020,"Ministerio de Salud y protección, Social; Instituto Nacional de, Salud",,,#1797,
,CZI,Orientaciones a puntos de entrada al país para el tamizaje de viajeros que vienen de zonas con circulación del nuevo coronavirus (2019-nCoV),,,,,El presente documento define lineamientos para realizar el tamizaje de los viajeros internacionales que ingresan al país; inicia con la identificación de viajeros por personal de Migración Colombia que son derivados para entrevista; continúa con la clasificación de potencial caso sospechoso y finaliza con la activación del plan de contingencias y emergencias del aeropuerto. This document defines guidelines for screening international travelers entering the country; it begins with the identification of travelers by Colombian Immigration personnel who are referred to interview; it continues with the classification of potential suspect case and ends with the activation of the airport&#039;s contingency and emergency plan.,2020,"Colombia. Ministerio de Salud y Protección, Social",,,#784,
,CZI,Protocolo para la atención de personas con sospechas o infección confirmada por Coronavirus (2019-nCoN),,,,,"El protocolo contiene definiciones de casos sospechosos, manejo de pacientes con sospecha de infección por Coronavirus, tratamiento específicos anti-Novel CoV e investigación clínica y las consideraciones especiales para pacientes embarazadas.",2020,"Perú. Ministerio de, Salud; Dirección General de Intervenciones Estratégicas en Salud, Pública",,,#1786,
,CZI,Protocolo para la atención de personas con sospechas o infección confirmada por Coronavirus (2019-nCoN)[Spanish],,,,,"El protocolo contiene definiciones de casos sospechosos, manejo de pacientes con sospecha de infección por Coronavirus, tratamiento específicos anti-Novel CoV e investigación clínica y las consideraciones especiales para pacientes embarazadas.",2020,"Perú. Ministerio de, Salud; Dirección General de Intervenciones Estratégicas en Salud, Pública",,,#1035,
,CZI,Protocolo de Manejo Clínico para o Novo Coronavírus (2019-nCoV),,,,,"Em 22 de janeiro de 2020, foi ativado o Centro de Operações de Emergências em Saúde Pública para o novo Coronavírus (COE ­ nCoV), estratégia prevista no Plano Nacional de Resposta às Emergências em Saúde Pública do Ministério da Saúde. O novo Coronavírus (2019-nCoV) é um vírus identificado como a causa de um surto de doença respiratória detectado pela primeira vez em Wuhan, China. Desde 2005, o Sistema Único de Saúde (SUS) está aprimorando suas capacidades de responder às emergências por síndromes respiratórias, dispondo de planos, protocolos, procedimentos e guias para identificação, monitoramento e resposta às emergências em saúde pública...",2020,"Brasil. Ministerio da Saúde. Secretaria de Atenção Especializada à Saúde. Departamento de Atenção Hospitalar, Domiciliar e de Urgência Coordenação-Geral de Urgência Força Nacional do Sistema Único de Saúde",,,#1864,
,CZI,Directrices de Laboratorio para la detección y diagnóstico de la Infección con el Nuevo Coronavirus 2019 (2019-nCoV),,,,,"En las directrices de laboratorio para la detección y diagnóstico de la infección con el nuevo coronovirus 2019 la Organización Panamericana de la Salud/Organización Mundial de la Salud (OPS/OMS) recomienda a los Estados Miembros garantizar su identificación oportuna, el envío de las muestras a laboratorios nacionales y de referencia y la implementación del protocolo de detección molecular para 2019-nCoV, según la capacidad del laboratorio.",2020,"Organización Panamericana de la, Salud",,,#749,
,CZI,"Update: Public Health Response to the Coronavirus Disease 2019 Outbreak — United States, February 24, 2020 | MMWR",,,,,"Fourteen cases have been diagnosed in the United States, in addition to 39 cases among repatriated persons from high-risk settings, for a current total of 53 cases within the United States. U.S. government agencies and public health partners are implementing aggressive measures to slow and try to contain transmission of COVID-19 in the United States.",2020,"Jernigan, Daniel B.",,,#1981,
,CZI,"Persons Evaluated for 2019 Novel Coronavirus — United States, January 2020 | MMWR",,,,,"Health care providers should remain vigilant about possible 2019 novel coronavirus (2019-nCoV) exposures not only among returning travelers from China, but also among those in close contact with persons with 2019-nCoV in the United States.",2020,"Kristina L. Bajema, MD1, 2; Alexandra M. Oster, MD3; Olivia L. McGovern, PhD1, 2; Stephen Lindstrom, PhD4; Mark R. Stenger, MA5; Tara C. Anderson, DVM, PhD6; Cheryl Isenhour, DVM2; Kevin R. Clarke, MD7; Mary E. Evans, MD8; Victoria T. Chu, MD1, 4; Holly M. Biggs, MD4; Hannah L. Kirking, MD4; Susan I. Gerber, MD4; Aron J. Hall, DVM4; Alicia M. Fry, MD9; Sara E. Oliver, MD2; Team, -nCoV Persons Under Investigation",MMWR,,#632,
,CZI,"The 2019 Novel Coronavirus Outbreak – Update From NIAID’s Anthony Fauci, MD",,,,,"In February 2020 the nature of the 2019-nCoV outbreak is still slowly coming into focus but it appears to be acting more like bad pandemic influenza (efficient spread, overall lower mortality) than like SARS (less efficient spread, overall higher mortality). Dr. Anthony Fauci of the US National Institute of Allergy and Infectious Diseases (NIAID) discusses the latest developments with JAMA Editor Howard Bauchner.Coronavirus Resource Center",2020,,,,#554,
,CZI,"Acciones en promoción de la salud, prevención y atención de la Infección Respiratoria Aguda - IRA- ante alerta internacional por Nuevo Coronavirus 2019-nCoV",,,,,"La Organización Mundial de Salud (OMS) informó la ocurrencia de casos de Infección Respiratoria Aguda Grave (IRAG) causada por un nuevo coronavirus (2019-nCoV) en Wuhan (China), desde la última semana de diciembre de 2019. Los primeros casos se presentaron en personas que estuvieron en un mercado de pescado y animales silvestres de Wuhan, no obstante, se han confirmado casos en personas que estuvieron en esta y otras zonas de China y en 20 países de 4 continentes. El 30 enero del 2020 la OMS declara emergencia de salud pública de importancia internacional (ESPII). The World Health Organization (WHO) reported the occurrence of cases of Acute Respiratory Infection Severe (IRAG) caused by a new coronavirus (2019-nCoV) in Wuhan, China, since last week December 2019. The first cases involved people who were in a fish and wildlife in Wuhan, however, cases have been confirmed in people who were in this and other areas of China and in 20 countries on 4 continents. On 30 January 2020 the WHO declares a public health emergency of international concern (ESPII).",2020,"Colombia. Ministerio de Salud y Protección, Social",,,#785,
,CZI,"In the pipeline Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine. All content is Derek’s own, and he does not in any way speak for his employer",,,,,"Let’s take inventory on the therapies that are being developed for the coronavirus epidemic. Here is a very thorough list of at Biocentury, and I should note that (like Stat and several other organizations) they’re making all their Covid-19 content free to all readers during this crisis. I’d like to zoom in today on the potential small-molecule therapies, since some of these have the most immediate prospects for use in the real world. The ones at the front of the line are repurposed drugs that are already approved for human use, for a lot of obvious reasons. The Biocentury list doesn’t cover these, but here’s an article at Nature Biotechnology that goes into detail. Clinical trials are a huge time sink – they sort of have to be, in most cases, if they’re going to be any good – and if you’ve already done all that stuff it’s a huge leg up, even if the drug itself is not exactly a perfect fit for the disease. So what do we have? The compound that is most advanced is probably remdesivir from Gilead, at right. This has been in development for a few years as an RNA virus therapy – it was originally developed for Ebola, and has been tried out against a whole list of single-strand RNA viruses. That includes the related coronaviruses SARS and MERS, so Covid-19 was an obvious fit. The compound is a prodrug – that phosphoramide gets cleaved off completely, leaving the active 5-OH compound GS-44-1524. It mechanism of action is to get incorporated into viral RNA, since it’s taken up by RNA polymerase and it largely seems to evade proofreading. This causes RNA termination trouble later on, since that alpha-nitrile C-nucleoside is not exactly what the virus is expecting in its genome at that point, and thus viral replication is inhibited.",2020,"Derek, Lowe; Doerffler, Edward; Clarke, Michael O.; Chun, Kwon; Zhang, Lijun; Neville, Sean; Carra, Ernest; Lew, Willard; Ross, Bruce; Wang, Queenie; Wolfe, Lydia; Jordan, Robert; Soloveva, Veronica; Knox, John; Perry, Jason; Perron, Michel; Stray, Kirsten M.; Barauskas, Ona; Feng, Joy Y.; Xu, Yili; Lee, Gary; Rheingold, Arnold L.; Ray, Adrian S.; Bannister, Roy; Strickley, Robert; Swaminathan, Swami; Lee, William A.; Bavari, Sina; Cihlar, Tomas; Lo, Michael K.; Warren, Travis K.; Mackman, Richard L.",,,#5177,
,CZI,‘This beast is moving very fast.’ Will the new coronavirus be contained—or go pandemic? | Science | AAAS,,,,,"Modelers are trying to forecast how the virus will move, but they need better data",2020,@NewsfromScience,,,#347,
,CZI,“The disruption is enormous.” Coronavirus epidemic snarls science worldwide | Science | AAAS,,,,,"Normal daily life has come to a virtual standstill in large parts of China as a result of the epidemic of COVID-19—and so has science. Universities across the country remain closed; access to labs is restricted, projects have been mothballed, field work interrupted, and travel severely curtailed. But scientists elsewhere in the world are noticing an impact as well, as collaborations with China are on pause and scientific meetings for the next five months have been canceled or postponed. The damage to science pales compared to the human suffering; the total number of cases has risen to 71,429, the World Health Organization (WHO) reported today, almost 99% of them in China, and there have been 1775 deaths. Still, for individual researchers the losses can be serious—and stressful. “Basically, everything has completely stopped,” says John Speakman, who runs an animal behavior lab at the Chinese Academy of Sciences (CAS) in Beijing that has effectively been shut since the Lunar New Year on 25 January. “The disruption is enormous. The stress on the staff is really high.” But Speakman says he understands why the Chinese government took the measures. “It’s annoying, but I completely support what they have done,” he says.",2020,"Service, Robert F.",,,#1115,
,CZI,Guidance on strengthening the management processes of children′s fever in outpatient department during the novel coronavirus pneumonia epidemic period (First Edition),,,,,"Novel Coronavirus Pneumonia (NCP) is a class B infectious disease, which is prevented and controlled according to class A infectious diseases. Recently, children&prime;s NCP cases have gradually increased, and children&prime;s fever outpatient department has become the first strategic pass to stop the epidemic. Strengthening the management of the fever diagnosis process is very important for early detection of suspected children, early isolation, early treatment and prevention of cross-infection. This article proposes prevention and control strategies for fever diagnosis, optimizes processes, prevents cross-infection, health protection and disinfection of medical staff, based on the relevant diagnosis, treatment, prevention and control programs of the National Health and Health Commission and on the diagnosis and treatment experience of experts in various provinces and cities. The present guidance summarizes current strategies on pre-diagnosis; triage, diagnosis, treatment, and prevention of 2019-nCoV infection in common fever, suspected and confirmed children, which provide practical suggestions on strengthening the management processes of children&prime;s fever in outpatient department during the novel coronavirus pneumonia epidemic period.",2020,"ZHANG, Guocheng; CHENG, Xiaoning; DING, Hui; SHI, Zhaoling; LI, Ruying; FU, Zhou; CHEN, Qiang; ZHAO, Dongchi; JIN, Runming; NIE, Guoming; LU, Jirong; LIU, Changshan; ZHAO, Deyu; PAN, Jiahua; FENG, Zhichun; SHI, Yuan; XIA, Zhengkun; ZHENG, Chengzhong; JIANG, Jinjin; WANG, Junxia; ZHENG, Yuejie; SHANG, Yunxiao; XIANG, Wei; XU, Baoping; SHEN, Kunling; WANG, Tianyou; YANG, Yonghong; LU, Quan",Chinese Journal of Applied Clinical Pediatrics,,#2066,
,CZI,Manual de bioseguridad para prestadores de servicios de salud que brinden atención en salud ante la eventual introducción del nuevo coronavirus (nCoV-2019) a Colombia,,,,,"Objetivo: Orientar a los Prestadores de Servicios de Salud del país sobre las normas de bioseguridad que se requieren implementar, frente a casos sospechosos o confirmados del nuevo coronavirus (nCoV-2019), con el fin de disminuir el riesgo de transmisión del virus de humano a humano durante la atención. En salud, evitando la presentación de casos en trabajadores de la salud, demás personal que labore en el ámbito de atención, y en otros pacientes que se encuentren en las instalaciones del prestador de servicios de salud. Objective: To provide guidance to the country&#039;s health service providers on the biosecurity standards that need to be implemented for suspected or confirmed cases of the new coronavirus (nCoV-2019), in order to reduce the risk of human-to-human transmission of the virus during care. In health, avoiding the presentation of cases in health workers, other personnel working in the care setting, and other patients in the health service provider&#039;s facilities.",2020,"Ministerio de Salud y Protección, Social",,,#937,
,CZI,‘A completely new culture of doing research.’ Coronavirus outbreak changes how scientists communicate | Science | AAAS,,,,,"On 22 January, Dave O’Connor and Tom Friedrich invited several dozen colleagues around the United States to join a new workspace on the instant messaging platform Slack. The scientists, both at the Wisconsin National Primate Research Center, had seen news about a new disease emerging in China and realized researchers would need a primate model if they were going to answer some important questions about its biology. “We put out a call to a bunch of investigators and basically said: ‘Hey, let’s talk,’” O’Connor says. The idea is to coordinate research and make sure results are comparable, Friedrich adds. (They named the Slack workspace the Wu-han Clan, a play on the hip-hop group Wu-Tang Clan.) The Wu-han Clan is just one example of how the COVID-19 outbreak is transforming how scientists communicate about fast-moving health crises. A torrent of data is being released daily by preprint servers that didn’t even exist a decade ago, then dissected on platforms such as Slack and Twitter, and in the media, before formal peer review begins. Journal staffers are working overtime to get manuscripts reviewed, edited, and published at record speeds. The venerable New England Journal of Medicine (NEJM) posted one COVID-19 paper within 48 hours of submission. Viral genomes posted on a platform named GISAID, more than 200 so far, are analyzed instantaneously by a phalanx of evolutionary biologists who share their phylogenetic trees in preprints and on social media.",2020,"Kupferschmidt, Kai",Science Magazine,,#2221,
,CZI,Novo Coronavírus: fluxo de atendimento na aps para o novo coronavírus (2019-NCOV),,,,,"priorizar o atendimento de casos suspeitos de novo Coronavírus, medidas de controle e registrar o atendimento no sistema de informação da Atenção Primária (SISAB)",2020,"Brasil. Ministerio da, Saude",,,#1865,
,CZI,"Lineamientos para la detección y manejo de casos por los prestadores de servicios de salud, frente a la eventual introducción del nuevo coronavirus (2019-ncov) a Colombia",,,,,"Propósito: orientar a los Prestadores de Servicios de Salud del país para la detección, atención y manejo de casos sospechosos de infección causada por el nuevo Coronavirus (nCoV-2019) para disminuir el riesgo de transmisión del virus de humano a humano. Purpose: to guide the country&#039;s health care providers in the detection, care, and management of suspected cases of infection caused by the new Coronavirus (nCoV-2019) in order to reduce the risk of human-to-human transmission of the virus.",2020,"Ministerio de Salud y Protección, Social",,,#936,
,CZI,Scientists question China’s decision not to report symptom-free coronavirus cases,,,,,"Researchers say that excluding these people could conceal the epidemic’s true extent, but others say the practice makes sense. Researchers are concerned that China’s official reports on the number of coronavirus infections have not been including people who have tested positive for the virus but who have no symptoms. They fear the practice is masking the epidemic’s true scale. But public health experts say China is right to prioritize tracking sick patients who are spreading the disease.",2020,Nature,Nature,,#1371,
,CZI,The race to unravel the United States’ biggest coronavirus outbreak,,,,,"Rohit Shankar left the virology laboratory at 2 a.m. on Wednesday, and was back at the lab bench by 7 a.m. the same day. “It’s okay,” he says, “I had a doughnut and a coffee.” Shankar, a medical scientist, and his colleagues at the University of Washington in Seattle are poised to exponentially drive up the number of confirmed cases of the coronavirus disease COVID-19 around the city, in western Washington state. That’s because this week, they began analysing a mountain of nose and throat swabs collected from hospitals in the region. Already, the researchers are seeing clear signs that the virus has infected vastly more people than have been formally detected. Scientists fear coronavirus spread in countries least able to contain it Washington state has become the United States’ ground zero for COVID-19, which has now spread to more than 90 countries worldwide in what seems to be a new and dangerous phase of the outbreak. Washington has declared a state emergency, and ten people there have died from the disease. But the number of confirmed cases in Washington — 70 — is still an underestimate resulting from a lack of testing, researchers agree. A genomic analysis posted online on 29 February suggested that hundreds of people in western Washington might already be infected. Academic scientists have mostly been prevented from measuring the extent of the US outbreak because of federal rules restricting the number of labs qualified to run diagnostic tests. But that is changing now, and helps account for why the state's caseload jumped from 10 to 70 this week. Dozens of virologists and genomicists have now kicked into high gear in Seattle, dropping or adapting projects to devote resources to the outbreak. Researchers are working around the clock to find out how many people have the disease in the area. Others are analysing genomes to reveal how the virus is transmitted or developing new therapies. The scientists are racing to help Washington avoid the fate of Hubei province in China, where more than 2,900 people have died of COVID-19 so far. The coronavirus emerged in the province’s city Wuhan in December, and the initial response from officials was slow. “We are past the point of containment,” says Helen Chu, an infectious-disease specialist at the University of Washington School of Medicine (UW Medicine) in Seattle. “So now we need to keep the people who are vulnerable from getting sick.”",2020,"Maxmen, Amy",,,#4900,
,CZI,Scientist decries ‘completely chaotic’ conditions on cruise ship Japan quarantined after viral outbreak | Science | AAAS,,,,,"SHARE Share on facebook 80 Share on twitter Share on linkedin Share on reddit 3 Share on mailto A port security officer at the Diamond Princess in Yokohama, Japan’s port. Passengers who tested negative for the coronavirus began to leave the cruise ship today. EUGENE HOSHIKO/AP Scientist decries ‘completely chaotic’ conditions on cruise ship Japan quarantined after viral outbreak By Dennis NormileFeb. 19, 2020 , 2:45 PM A Japanese infectious disease specialist has harshly criticized the way Japan’s government has handled the COVID-19 crisis aboard a luxury cruise ship docked in Yokohama. Conditions on board the Diamond Princess were “violating all infection control principles” and “completely chaotic,” the scientist, Kentaro Iwata of Kobe University, said in a YouTube video posted on Tuesday evening. His claims are inflaming an already intense debate over Japan’s handling of the crisis. Scientists have also faulted the slow release of epidemiological data about the ship that could help control efforts elsewhere.",2020,"Normile, Dennis",,,#1279,
,CZI,The United States badly bungled coronavirus testing—but things may soon improve | Science | AAAS,,,,,"Speed is critical in the response to COVID-19. So why has the United States been so slow in its attempt to develop reliable diagnostic tests and use them widely? The World Health Organization (WHO) has shipped testing kits to 57 countries. China had five commercial tests on the market 1 month ago and can now do up to 1.6 million tests a week; South Korea has tested 65,000 people so far. The U. S. Centers for Disease Control and Prevention (CDC), in contrast, has done only 459 tests since the epidemic began. The rollout of a CDC-designed test kit to state and local labs has become a fiasco because it contained a faulty reagent. Labs around the country eager to test more suspected cases—and test them faster—have been unable to do so. No commercial or state labs have the approval to use their own tests. In what is already an infamous snafu, CDC initially refused a request to test a patient in Northern California who turned out to be the first probable COVID19 case without known links to an infected person.",2020,"Cohen, Jon",Science Magazine,,#2779,
,CZI,Daily briefing: World’s biggest physics meeting cancelled over coronavirus fears,,,,,The March Meeting of the APS was cancelled just 36 hours before it was scheduled to begin today. Plus: the best repositories for life-sciences imaging data and how to find early-career grants and fellowships.,2020,"Graham, Flora",Nature,,#3172,
,CZI,How Coronaviruses Cause Infection—from Colds to Deadly Pneumonia,,,,,The novel coronavirus outbreak raises questions about how such pathogens evolve and what makes infections mild or severe,2020,"Makin, Simon",,,#294,
,CZI,Advices on the prevention and control of nosocomial infection of novel coronavirus within children’s hospitals,,,,,"The pneumonia caused by the novel coronavirus (2019-nCoV), which began in December 2019, has become the most serious public health problem, threatening people's health and life. This threat is posing a severe challenge on the diagnosis and treatment of 2019-nCoV infection, the prevention and control of hospital cross infection of medical staff. It is suggested that in addition to strengthening the organization and leadership of the abovementioned work, establishing and improving the prevention and control mechanism deserve greater attention. Furthermore, special attention should be given to the safety of the medical staff, strengthening their infection monitoring and outbreak management. Medical staff in different work areas and positions should be placed under careful protection, cleaning and disinfection measures. The protection during specimen collection, transportation and medical waste management should also be prioritized. This paper also put forward management suggestions for the outpatient department, isolation ward and other key departments. These measures are proposed to provide a guidance for the prevention and control of 2019-nCoV nosocomial infection in the pediatric outpatient and ward.",2020,"XU, Hongzhen; CHEN, Shuohui; FU, Junfen; SHU, Qiang; CHEN, Zhimin; SUN, Wei; WANG, Dan; ZHU, Haihong; ZHOU, Hongqin; HUANG, Guolan; FU, Zangzang; ZHAO, Hangyan; WANG, Bin; WU, Xiaoqing; LIANG, Yuqin; HUANG, Yufen; GU, Meihong; WANG, Wei",Chinese Journal of Hospital Administration,,#2106,
,CZI,‘This beast is moving very fast.’ Will the new coronavirus be contained—or go pandemic?,,,,,"The silver lining of the epidemic is that scientists have collected and shared information at record speed. “Every day that goes by we know more and every day that goes by we can do better modeling,” Vespignani says. “Unfortunately, this beast is moving very fast.”",2020,"Cohen, Kai Kupferschmidt; Jon",Science,,#332,
,CZI,Novo Coronavírus: atendimento a pessoas com suspeita de infecção pelo novo coronavírus (2019-nCoV) na Atenção Primária à Saúde,,,,,,2020,"Brasil. Ministerio da, Saude",,,#1866,
,CZI,Novo coronavirus (2019 nCov) Medidas de prevenção e controle de infecção a serem adotadas na ssistência à saúde,,,,,,2020,"São Paulo Secretaria da, Saúde",,,#922,
,CZI,The prevention and control of a new coronavirus infection in department of stomatology,,,32057210,,"During a short period of time, the outbreak of pneumonia caused by a novel coronavirus, named Novel Coronavirus Pneumonia (NCP), was first reported in China, spreading to 24 countries and regions rapidly. The number of confirmed cases and deaths continued to rise. World Health Organization (WHO) announced that the outbreaks of the novel coronavirus have constituted a Public Health Emergency of International Concern. Efficient infection control can prevent the virus from further spreading, which makes the epidemic situation under control. Due to the specialty of oral healthcare settings, the risk of cross infection is severe among patients and oral healthcare practitioners. It's more urgent to implement strict and efficient infection control protocols. This paper, based on existing guidelines and published researches pertinent to dental infection-control principles and practices, mainly discusses epidemiological characteristics of NCP and the features of nosocomial infection in oral healthcare settings, and furthermore provides recommendations on patient's evaluation, and infection control protocols in department of stomatology under current circumstance..",2020,"LI, Zhi yong; MENG, Liu yan",Chinese Journal of Stomatology,2377782053,#1228,
,CZI,COVID-19: another infectious disease emerging at the animal-human interface,,,32078596,,,2020,"Murdoch, David R.; French, Nigel P.",N Z Med J,2185518228,#1541,
,CZI,Dynamic changes of chest CT imaging in patients with corona virus disease-19 (COVID-19),,,32096366,,"OBJECTIVE: To analyze the dynamic changes of chest CT images of patients with corona virus disease-19 (COVID-19). METHODS: Fifty-two cases of COVID-19 were admitted in the First Affiliated Hospital of Zhejiang University School of Medicine. The consecutive chest CT scans were followed up for all patients with an average of 4 scans performed per patient during the hospitalization. The shortest interval between each scan was 2 days and the longest was 7 days. The shape, number and distribution of lung shadows, as well as the characteristics of the lesions on the CT images were reviewed. RESULTS: The obvious shadows infiltrating the lungs were shown on CT images in 50 cases, for other 2 cases there was no abnormal changes in the lungs during the first CT examination. Ground-glass opacities (GGO) were found in 48 cases (92.3%), and 19 cases (36.5%) had patchy consolidation and sub-consolidation, which were accompanied with air bronchi sign in 17 cases (32.7%). Forty one cases (78.8%) showed a thickened leaflet interval, 4 cases (7.6%) had a small number of fibrous stripes. During hospitalization, GGO lesions in COVID-19 patients gradually became rare, the fibrous strip shadows increased and it became the most common imaging manifestation. The lesions rapidly progressed in 39 cases (75.0%) within 6-9 days after admission. On days 10-14 of admission, the lesions distinctly resolved in 40 cases (76.9%). CONCLUSIONS: The chest CT images of patients with COVID-19 have certain characteristics with dynamic changes, which are of value for monitoring disease progress and clinical treatment.",2020,"Wang, Jincheng; Liu, Jinpeng; Wang, Yuanyuan; Liu, Wei; Chen, Xiaoqun; Sun, Chao; Shen, Xiaoyong; Wang, Qidong; Wu, Yaping; Liang, Wenjie; Ruan, Lingxiang",Zhejiang Da Xue Xue Bao Yi Xue Ban,2349102525,#1922,
,CZI,Novel coronavirus COVID-19: an overview for emergency clinicians,,,32105049,,"Prior to the global outbreak of SARS-CoV in 2003, HCoV-229E and HCoV-OC43 were the only coronaviruses known to infect humans. Following the SARS outbreak, 5 additional coronaviruses have been discovered in humans, most recently the novel coronavirus COVID-19, believed to have originated in Wuhan, Hubei Province, China. SARS-CoV and MERSCoV are particularly pathogenic in humans and are associated with high mortality. In this review, the epidemiology, pathophysiology, and management of the recently discovered COVID-19 are reviewed, with a focus on best practices and the public health implications.",2020,"Giwa, A.; Desai, A.",Emergency medicine practice,3005413696,#2815,
,CZI,"Coronavirus 9-nCoV: recomendaciones para aeropuertos, puertos y pasos fronterizos",,,,,"Ante la situación mundial, en relación a 2019-nCoV, que implica la posibilidad de ingreso a nuestro país de personas infectadas, se generaron las recomendaciones necesarias para la detección temprana y control de pacientes con posibilidad de presentar una enfermedad respiratoria aguda al ingreso a nuestro país. La principal estrategia es la detección temprana y control de los casos posibles. En los Aeropuertos, Puertos y Pasos Fronterizos se está realizando difusión masiva de información para viajeros en relación a 2019-nCoV, con el objetivo de generar conciencia acerca de la importancia de las medidas de prevención, los síntomas ante los cuales se debe solicitar atención y el teléfono de consulta ministerial sanitaria (0800-222-1002 - opción 1)",2020,"Argentina. Ministerio de, Salud",,1604377110,#801,
,CZI,Novel Coronavirus Disease 2019 (COVID-19): An Emerging Infectious Disease in the 21st Century,,,,,"Background: At the beginning of the New Year 2020, China alerted the world health organization (WHO) to a cluster of unusual pneumonia cases in Wuhan. After extensive speculation, eventually a new species of coronavirus introduced as the causative pathogen of the disease. Coronavirus disease 2019 (COVID-19) is a name for the disease, and the virus that causes it is known SARS-CoV-2. The very rapid spread of the COVID-19 in China and in many other countries has caused fear among people across the world. The novel coronavirus outbreak declared a Public Health Emergency of International Concern on 30 January 2020. Materials and Methods: Several databases such as PubMed, Scopus, Google scholar, and BioRxiv were searched for publications reporting on the novel coronavirus up to 29 February 2020. Literature searches were performed using keywords including “Coronavirus 2019”, “2019-nCoV”, “COVID-19”, and “SARS-CoV-2”. Moreover, websites such as the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) were searched to retrieve updated data and statistics regarding the novel coronavirus. We extracted data on the epidemiology, pathogenesis, virology, clinical manifestations, transmission routes, diagnosis, treatment, and prevention measures. Results: From the 1416 articles identified in the initial search, 53 were remained after title and abstract screening. After full-text review, 37 articles were eligible to include in our study. Incubation period for COVID-19 is between 2-10 days, according to the World Health Organization (WHO). The case fatality rate in patients infected with SARC-CoV-2 is 4.3%, and the results indicate that the mortality is higher in elderly individuals and patients with chronic conditions including patients with coronary artery disease, diabetes, chronic pulmonary disease, and hypertension. The mortality rate in healthy subjects is less than 1%. Conclusion: The outbreak caused by the novel coronavirus is larger than the previous human coronaviruses, showing that the SARS-CoV-2 is an extremely contagious virus. However, the mortality rate of COVID-19 is lower than that of other coronaviruses diseases such as SARS or MERS and other viruses like HIV and Ebola. Currently, due to the lack of an effective treatment and vaccine, the best way to deal with the COVID-19 disease is to prevent transmission and spread of the virus and to execute personal protective measures.",2020,"Keshavarz, Ahmad Tavakoli; Katayon, Vahdat; Mohsen",Iranian South Medical Journal,621380834,#4536,
,CZI,Coronavirus just caused the American Physical Society to cancel its biggest meeting of the year | Science | AAAS,,,,,"Citing the growing threat of the coronavirus, the American Physical Society (APS), the 55,000 member professional society for physicists and researchers in associated fields, cancelled its largest meeting of the year just 34 hours before it was supposed to begin. APS’s March Meeting was to be held this week at the Colorado Convention Center in Denver, and the society anticipated more than 10,000 people from all over the world would attend. However, late yesterday, APS issued a statement abruptly calling off the meeting. “The decision to cancel was based on the latest scientific data being reported, and the fact that a large number of attendees at this meeting are coming from outside the U.S.,” including countries where the virus is circulating and for which the U.S. Centers for Disease Control and Prevention have advised people to avoid non-essential travel, the APS statement says. “[T]his decision was made out of deep concern for the health and well-being of our registrants, staff, vendors, and the Denver community.”",2020,"Cho, Adrian",Science Magazine,2595674569,#2772,
,CZI,Mensajero de la Salud: nuevo coronavirus 2019-nCoV,,,,,Declaratoria de Emergencia en Salud Pública de importancia Internacional por el nuevo coronavirus 2019-nCoV,2020,"Mexico. Secretaria de la, Salud",,3003591461,#1803,
,CZI,The management of biosafety risk in clinical laboratory of hospital during the outbreak of 2019 Novel Coronavirus disease,,,,,"During the outbreak of coronavirus disease-19 (COVID-19), the clinical laboratories of hospitals designated for the disease treatment is undertaking a lot of clinical testing work of infectious specimens. How to manage the biosafety risk is a major problem that the clinical laboratory and the nosocomial infection control department are facing. This article introduces the hierarchical prevention and control biosafety measures in the clinical laboratory from the perspective of the laboratory, with a view to provide reasonable and feasible methods for the clinical laboratories of hospitals at various levels during the outbreak.",2020,"XIAO, Yuling; LU, Xiaojun; KANG, Mei; LI, Dongdong; JIANG, Hong; CHEN, Jie; YING, Binwu; XIE, Yi",Chinese Journal of Laboratory Medicine,2194450012,#2110,
,CZI,Lineamiento estandarizado para la Vigilancia Epidemiologica y por laboratorio de enfermedad por 2019-NCoV,,,,,"Este documento describe la situación epidemiológica de la enfermedad por 2019-nCoV, los lineamientos para la detección y seguimiento de los casos, así como los aspectos de la toma, manejo y envío adecuado de las muestras y el control analítico disponible para la confirmación de los casos.",2020,"Mexico. Secretaria de Salud. Subsecretaria de Prevencion y Promoción de la Salud. Dirección General de, Epidemiologia",,2241123449,#1802,
,CZI,Singapore claims first use of antibody test to track coronavirus infections | Science | AAAS,,,,,"In what appears to be a first, disease trackers in Singapore have used an experimental antibody test for COVID-19 to confirm that a suspected patient was infected with the coronavirus. The patient was one of two people who together formed a missing link between two clusters of cases that each occurred in a Singaporean church. Researchers around the world are racing to develop antibody tests, also called serological tests, that can confirm whether someone was infected even after their immune system has cleared the virus that causes COVID-19. The group that developed the test, at Duke-NUS Medical School in Singapore, is among the front-runners, although its assay has to be validated before it is taken into production and deployed widely.",2020,"Normile, Dennis",Science Magazine,2855667717,#2584,
,CZI,"The network investigation on knowledge, attitude and practice about Novel coronavirus pneumonia of the residents in Anhui Province",,,,,"Objective To analyze the current situation of the knowledge, attitudes and practice about Novelcoronavirus pneumonia (NCP) of the residents in Anhui Province. Methods Anonymous network sampling survey was carried out with an electronic questionnaire that designed by the questionnaire star, and a total of 4016 subjects from Anhui province were investigated. The content of the survey includes that the basic information of subjects,the residents' knowledge, attitudes and practice about NCP, as well as their satisfaction with the prevention and control measures adopted by the government and health authorities and the suggestions on future prevention. The questionnaire doesn't involve any privacy information, and all questions were mandatory to ensure the response rate. Results The M(P 25 , P 75 )age the 4 016 subjects was 21 (19, 24) years old, and the ranging from 7 to 80 years old. The number of males was 1 431(35.6%). Social networking tools such as WeChat and QQ were the main sources of epidemic information for residents (97.8%, 3 929 respondents). Residents had higher awareness rate of cough (99.5%, n= 3 997) and fever(96.0%, n= 3 857) symptoms, the transmission by droplets (99.5%, n= 3 995), aerosol transmission (81.1%, n= 3 258), and contact transmission (92.3%, n= 3 708), but lower awareness of symptoms os muscle pain or fatigue (62.7%, n= 2 518). 92.6% of the subjects ( n= 3 720) think that the outbreak was scary. In terms of psychological behavior scores, the results showed that female (9.38&plusmn;4.81), the urban (9.37&plusmn;5.02) and the medical workers (10.79&plusmn;5.19) had a poorer mental health than the male (8.45&plusmn;5.00), the rural (8.71&plusmn;4.75) and the non-medical workers (the students: 8.85&plusmn;4.83; public institude workers: 9.02&plusmn;5.08; others: 8.97&plusmn;5.39) ( P &lt;0.05). 71.9% of the residents ( n= 2 887)were satisfied with the local epidemic control measures. The residents took various of the measures to prevent and control the epidemic. The ratio of residents that could achieve'no gathering and less going out','wear masks when going out'and'do not go to crowded and closed places'was up to 97.4% ( n= 3 913), 93.6% ( n= 3758) and 91.5% ( n= 3 673) respectively. Conclusion The residents in Anhui province have a good KAP about NCP, yet it is necessary to strengthen the community publicity, the mental health maintenance of residents and students' health education.",2020,"CHEN, Yan",Chinese Journal of Preventive Medicine,2363410972,#2333,
,CZI,Investigation on demands for antenatal care services among 2 002 pregnant women during the epidemic of coronavirus disease 2019 in Shanghai,,,,,"Objective To identify problems and demands for antenatal care (ANC) among pregnant women in different trimesters of pregnancy in Shanghai for optimizing ANC service during the epidemic of coronavirus disease 2019 (COVID-19). Methods Organized by Maternal and Child Health Care institute in the 16 districts of Shanghai, a cross sectional study was conducted among pregnant women who came to pregnancy registration in the community health centers or attended ANC in maternity hospitals from February 7 to February 12, 2020. Consented participating women completed a semi-structured online questionnaire voluntarily. Data was analyzed using frequency and scoring, chi-square test. Results A total of 2 002 valid questionnaires were collected from 183 community health centers and 67 midwifery hospitals. About 94.6% of the pregnant women worried about being infected during the COVID-19 epidemic, and 14.7% demanded for psychological consultation. Appointment ANC services were requested by 87.7% of the participants for avoiding presenting themselves in people-density places. Compared with other pregnancy trimesters, pregnant women in the second trimester were more willing to reduce the frequency of ANC (48.1% VS. 39.5% VS. 35.2%, P &lt;0.01). Compared with multiparas, primiparas were more willing to have online consultation and guidance (63.8% VS. 49.2%, P &lt;0.01). Regarding the needs for health knowledge on COVID-19, personal protection against 2019-nCoV was the most concerned for pregnant women, and 71.0% of them preferred to obtain knowledge through health applications, official Weibo and WeChat. Conclusions Pregnant women in Shanghai critically concern about the risk of 2019-nCoV infections, and highly demand knowledge and measures on prevention and protection from COVID-19. They ask for having time-lapse appointments for ANC and online access to health information and services. Maternal and Child Care institutes should understand the demands of pregnant women, optimize the means of ANC service, and provide tailored and accessible health education and service for the safety of mother and child.",2020,"DU, Li; GU, Yibin; CUI, Mengqing; LI, Wenxian; WANG, Jie; ZHU, Liping; XU, Biao",Chinese Journal of Obstetrics and Gynecology,1891209719,#2305,
,CZI,Analysis of early chest high resolution CT images of novel coronavirus pneumonia,,,,,"Objective To investigate the first chest HRCT imaging manifestations infected with novel coronavirus pneumonia (NCP). Method A retrospective analysis of the first chest HRCT images of 106 patients with NCP clinically diagnosed in our hospital from January 3 to 25, 2020. Lesion distribution, morphology and surrounding involvement were analyzed. Result Lesions were found in the first lung HRCT of 106 patients, with unilateral lung distribution in 11 cases (10.4%), bilateral lung distribution in 95 cases (89.6%), and peripheral distribution of lung in 65 cases (61.3%). 41 cases (38.7%) were distributed at the same time; 8 cases (7.5%) were 1 lesion, 5 cases (4.7%) were 2 lesions, 93 cases (87.8%) were multiple lesions, and 12 cases were nodular lesions (11.3%). 94 cases of ground-glass lesions (88.7%), 7 cases of cord-like lesions (6.6%), 15 cases (14.2%) of coexisting lesions of two or more forms; 10 cases (9.4%) involving one lung lobe There were 96 cases (90.6%) involving two or more lung lobes; 24 cases (22.6%) with enlarged mediastinal lymph nodes (19 cases over 60 years old, accounting for 79.2%); 3 cases with pleural effusion (2.8 %), 1 case had pericardial effusion (0.9%), and 2 cases had pleural involvement / thickening (1.9%). Patients over 60 years of age mostly present with multiple lesions, multiple morphology, peripheral and central distribution of lungs, involving multiple lung lobes, and enlarged mediastinal lymph nodes. Conclusions Lung lesions of NCP patients can be detected for the first time by chest HRCT, which is the preferred imaging method. Thoracic HRCT scans play an important role in the early diagnosis of new coronavirus (NCP). .",2020,"LIU, Haifeng; ZHANG, Dongyou; YANG, Yi; LONG, Bin; YIN, Long; ZHAO, Ming; PENG, Yong",Chinese Journal of Radiology,2418493795,#2187,
,CZI,Novo Coronavirus (nCoV),,,,,"Os Coronavírus (CoV) compõem uma grande família de vírus, conhecidos desde meados da década de 1960. Podem causar desde um resfriado comum até síndromes respiratórias graves, como a síndrome respiratória aguda grave (SARS - Severe Acute Respiratory Syndrome) e a síndrome respiratória do Oriente Médio (MERS - Middle East Respiratory Syndrome). Os casos agora identificados estão relacionados a uma nova variante do Coronavírus, denominada 2019-nCoV, até então não identificada em humanos.",2020,"Rio de Janeiro . Secretaria de Estado de Saúde. Subsecretaria de Vigilância em, Saúde",Nota Técnica-SVS/SES-RJ,2518954822,#216,
,CZI,Difficulties and strategies of public hospitals in their participation in the prevention and control of novel coronavirus pneumonia,,,,,"Outbreak of the novel coronavirus pneumonia (NC) across the country has seriously threatened people's lives and health, endangering smooth operation of the national economy and social stability. An all-out campaign to save the NCP patients and reduce their mortality is not only one of the key tasks to fight against the epidemic, but also a major responsibility and mission of public hospitals. In view of the field practice of Wuhan Union Hospital in the epicenter, the authors Described the challenges faced by such hospitals in the prevention and control, summarized its experiences and proposed improvement measures, for reference of other public hospitals and relevant authorities.",2020,"XU, Dong; HU, Yu; DING, Ning; XIA, Jiahong; ZHANG, Yidan; WEI, Li; ZHANG, Ming; WAN, Jie",Chinese Journal of Hospital Administration,2348898337,#2108,
,CZI,Get Real,,,,,"Since this is going to be a post about the coronavirus, let’s start off with this PSA: wash your hands. ... OK, either tomorrow or Friday I hope to do a post on all the things that are going on in the biopharma industry for a possible coronavirus treatment. ... It was clearly related to the virus from the first case (reported on January 19 in the same county in Washington state), descended from it in a way that makes it almost certain that the coronavirus has been spreading undetected among that population for weeks.",2020,"Lowe, Derek",Science,2343731596,#3808,
,CZI,How Ophthalmologists Should Understand and Respond to the Current Epidemic of Novel Coronavirus Pneumonia (COVID-19),,,,,"The new coronavirus pneumonia that first appeared in Wuhan, China, in December 2019 has attracted great attention from both the Chinese government and the international community. The International Committee on Viral Classification named the virus 'Severe Acute Respiratory Syndrome Coronavirus 2' (SARS-CoV-2), and the WHO named the pneumonia it causes 'Coronavirus Disease 2019' (COVID-19). At present, the disease is centered in Wuhan City and is spreading rapidly to all parts of China, as well as twenty other countries. About 20% of the people infected during the SARS epidemic in 2003 were employees in hospital environments. COVID-19 has infected an even greater number of heath care workers. Therefore, ophthalmologists need to understand the disease and recognize the importance of taking preventive measures. Although ophthalmologists do not work on the front lines of the outbreak, due to their area of expertise, a variety of situations, such as infection consultations or ophthalmic emergency treatments, can lead to the exposure of ophthalmologists to high-risk environments. This risk will only increase as the number of infected patients continues to increase. When dealing with seemingly normal ophthalmic patients, the vigilance of ophthalmologists and associated staff tends to be significantly reduced. To better protect patients, families, and health care workers, it is strongly recommended that in addition to the standard precautions for the care of all patients, strict contact precautions and droplet precautions need to be taken by ophthalmologists. These measures include 1) wearing an efficient mask (an N95 mask); 2) always performing hand hygiene before and after examining a patient; (3) wearing sterile gloves when entering a patient&rsquo;s room and touching a patient; (4) wearing a gown when contact is expected with items and environmental surfaces surrounding a patient or when the patient is incontinent or has diarrhea or a surgical or other invasive wound with oozing fluid; 5) cleaning and disinfecting ophthalmic equipment and correctly handling medical waste after examination to prevent transmission to patients who are subsequently examined; 6) wearing goggles and a disposable mask to cover the front and sides of the face before touching a patient, as the virus could spread through the ocular surface; 7) performing the relevant screening for novel coronavirus pneumonia for regular patients who have conjunctivitis and respiratory symptoms at the same time; 8) prohibiting the use of infected patients as potential donors for corneal transplants and temporarily adding donor SARS-CoV-2 screening to the medical standard of the eye bank during the outbreak; and 9) for the purposes of scientific research, diagnosis, and other special needs, packing, shipping, and transporting collected specimens according to the relevant dangerous biological goods regulations.",2020,"ZHIJIE, Li",Chinese Journal of Experimental Ophthalmology,3005943294,#2051,
,CZI,Experts proposal and frequently asked questions of rapid screening and prevention of novel coronavirus pneumonia in children,,,,,"The outbreak of novel coronavirus pneumonia (NCP) has become the most severe public health issue at the moment, threatening people&prime;s lives. Pediatricians in Shanghai have recently launched a discussion on the focused questions of NCP, including the incidence situation, epidemiological features, essentials of early screening, treatment and nosocomial infection prevention of children&prime;s novel coronavirus infection (2019-nCoV), and further put forward the experts proposal upon the patterns of disease occurrence, development, diagnosis and control, for the reference of frontline pediatricians.",2020,"ZHANG, Lei; CAO, Qing; WANG, Ying; LU, Quan; HONG, Jianguo; YIN, Yong; ZHANG, Xiaobo; ZHANG, Jianhua; LU, Min; DONG, Xiaoyan; LU, Yanming; ZHANG, Jing; ZHANG, Jian",Chinese Journal of Applied Clinical Pediatrics,2416639376,#2063,
,CZI,Surgical treatment strategy for digestive system malignancies during the outbreak of novel coronavirus pneumonia,,,,,"The outbreak of novel coronavirus pneumonia occurred in Wuhan, Hubei province of China, at the end of 2019, and spread rapidly across the country. After the outbreak of this disease, the overwhelming majority of cities have launched the 'first level response' and the regular diagnosis and treatment of cancer patients are greatly affected. The digestive systemic cancer is the most common malignancy. Most patients are diagnosed in the advanced stage with poor prognosis. The epidemic of novel coronavirus pneumonia poses new challenges to diagnosis and treatment of the patients with digestive system malignancies. Based on the fully understanding of the characteristics of digestive system tumors, we should change the treatment strategy and adopt more reasonable treatment strategy timely during the epidemic period to minimize the adverse effects of the epidemic of novel coronavirus pneumonia on the treatment.",2020,"MA, Fuhai; HU, Haitao; TIAN, Yantao",Chinese Journal of Oncology,2366820445,#2176,
,CZI,Novel coronavirus pneumonia in the primary general hospital of treatment based on traditional Chinese medicine syndrome differentiation and prevention,,,,,"To observe the curative effect of TCM syndrome differentiation and treatment for novel coronavirus pneumonia (novel coronavirus pneumonia, NCP) patients and the preventive effect for Chinese medical staff. Methods. A total of 62 NCP suspected patients admitted in 2020 were treated with TCM syndrome differentiation and treatment, as well as our hospital medical staff with No.1-4 hospital prescription. After taking traditional Chinese medicine, 16 out of 25 NCP suspected patients with phlegm heat stagnating lung syndrome were discharged to home for isolation observation, 4 patients hospitalized for observation, and 5 patients confirmed with NCP. For 15 patients with phlegm dampness accumulating lung syndrome, 7 patients were discharged to home for isolation observation, 3 patients were hospitalized for observation and 5 patients have been confirmed. For 18 patients with spleen stomach disharmony syndrome, 15 patients were discharged to home for isolation observation, 1 patient was hospitalized for observation and 2 patients have been confirmed. For 4 patients with Qi deficiency and dampness stagnation syndrome were discharged to home for isolation observation, 1 patient was hospitalized for observation, and two have been confirmed. The duration of taking traditional Chinese medicine was 1 to 20 days from admission to be discharged. The doctors and nurses who took the prescription of TCM for 12 to 15 days have been prevented from NCP infection. Conclusions. The clinical effect and the preventive effect of TCM syndrome differentiation and treatment for NCP have been proved to be satisfactory. TCM can go into the primary hospital for treatment and prevention on NCP.",2020,"Liao, Rongye; Yang, Jie; Cao, Zhi; Wang, Jun",International Journal of Traditional Chinese Medicine,2616653490,#1962,
,CZI,"A Novel Coronavirus Outbreak from Wuhan City in China, Rapid Need for Emergency Departments Preparedness and Response; a Letter to Editor",,,,,,2020,"Alavi-Moghaddam, Mostafa",Archives of Academic Emergency Medicine,3006236663,#3509,
,CZI,History is repeating itself: Probable zoonotic spillover as the cause of the 2019 novel coronavirus epidemic,,,,,,2020,"Rodriguez-Morales, A. J.; Bonilla-Aldana, D. K.; Balbin-Ramon, G. J.; Rabaan, A. A.; Sah, R.; Paniz-Mondolfi, A.; Pagliano, P.; Esposito, S.",Infezioni in Medicina,3005681200,#926,
,CZI,"Epidemiological and Clinical Characteristics of 99 Cases of 2019-Novel Coronavirus (2019-nCoV) Pneumonia in Wuhan, China",,,,,,,"Chen, Nanshan and Zhou, Min and Dong, Xuan and Qu, Jieming and Gong, Fengyun and Han, Yang and Qiu, Yang and Wang, Jingli and Liu, Ying and Wei, Yuan and Xia, Jia'an and Yu, Ting and Zhang, Xinxin and Zhang, Li,",,3004580727,#22,
03203ab50eb64271a9e825f94a1b1a6c46ea14b3,PMC,Recombination Every Day: Abundant Recombination in a Virus during a Single Multi-Cellular Host Infection,http://dx.doi.org/10.1371/journal.pbio.0030089,PMC1054884,15737066,CC BY,"Viral recombination can dramatically impact evolution and epidemiology. In viruses, the recombination rate depends on the frequency of genetic exchange between different viral genomes within an infected host cell and on the frequency at which such co-infections occur. While the recombination rate has been recently evaluated in experimentally co-infected cell cultures for several viruses, direct quantification at the most biologically significant level, that of a host infection, is still lacking. This study fills this gap using the cauliflower mosaic virus as a model. We distributed four neutral markers along the viral genome, and co-inoculated host plants with marker-containing and wild-type viruses. The frequency of recombinant genomes was evaluated 21 d post-inoculation. On average, over 50% of viral genomes recovered after a single host infection were recombinants, clearly indicating that recombination is very frequent in this virus. Estimates of the recombination rate show that all regions of the genome are equally affected by this process. Assuming that ten viral replication cycles occurred during our experiment—based on data on the timing of coat protein detection—the per base and replication cycle recombination rate was on the order of 2 × 10(−5) to 4 × 10(−5). This first determination of a virus recombination rate during a single multi-cellular host infection indicates that recombination is very frequent in the everyday life of this virus.",2005 Mar 1,"['Froissart, Remy', 'Roze, Denis', 'Uzest, Marilyne', 'Galibert, Lionel', 'Blanc, Stephane', 'Michalakis, Yannis']",PLoS Biol,,,True
98a3b0606a67d829816c1d934e2d1a7196985151,PMC,Prospective evaluation of an internet-linked handheld computer critical care knowledge access system,http://dx.doi.org/10.1186/cc2967,PMC1065064,15566586,CC BY,"INTRODUCTION: Critical care physicians may benefit from immediate access to medical reference material. We evaluated the feasibility and potential benefits of a handheld computer based knowledge access system linking a central academic intensive care unit (ICU) to multiple community-based ICUs. METHODS: Four community hospital ICUs with 17 physicians participated in this prospective interventional study. Following training in the use of an internet-linked, updateable handheld computer knowledge access system, the physicians used the handheld devices in their clinical environment for a 12-month intervention period. Feasibility of the system was evaluated by tracking use of the handheld computer and by conducting surveys and focus group discussions. Before and after the intervention period, participants underwent simulated patient care scenarios designed to evaluate the information sources they accessed, as well as the speed and quality of their decision making. Participants generated admission orders during each scenario, which were scored by blinded evaluators. RESULTS: Ten physicians (59%) used the system regularly, predominantly for nonmedical applications (median 32.8/month, interquartile range [IQR] 28.3–126.8), with medical software accessed less often (median 9/month, IQR 3.7–13.7). Eight out of 13 physicians (62%) who completed the final scenarios chose to use the handheld computer for information access. The median time to access information on the handheld handheld computer was 19 s (IQR 15–40 s). This group exhibited a significant improvement in admission order score as compared with those who used other resources (P = 0.018). Benefits and barriers to use of this technology were identified. CONCLUSION: An updateable handheld computer system is feasible as a means of point-of-care access to medical reference material and may improve clinical decision making. However, during the study, acceptance of the system was variable. Improved training and new technology may overcome some of the barriers we identified.",2004 Oct 14,"['Lapinsky, Stephen E', 'Wax, Randy', 'Showalter, Randy', 'Martinez-Motta, J Carlos', 'Hallett, David', 'Mehta, Sangeeta', 'Burry, Lisa', 'Stewart, Thomas E']",Crit Care,,,True
d617306cda56236d02117ae7a5fc5e7fcd015554,PMC,Subversion of Cellular Autophagosomal Machinery by RNA Viruses,http://dx.doi.org/10.1371/journal.pbio.0030156,PMC1084330,15884975,CC BY,"Infection of human cells with poliovirus induces the proliferation of double-membraned cytoplasmic vesicles whose surfaces are used as the sites of viral RNA replication and whose origin is unknown. Here, we show that several hallmarks of cellular autophagosomes can be identified in poliovirus-induced vesicles, including colocalization of LAMP1 and LC3, the human homolog of Saccharomyces cerevisiae Atg8p, and staining with the fluorophore monodansylcadaverine followed by fixation. Colocalization of LC3 and LAMP1 was observed early in the poliovirus replicative cycle, in cells infected with rhinoviruses 2 and 14, and in cells that express poliovirus proteins 2BC and 3A, known to be sufficient to induce double-membraned vesicles. Stimulation of autophagy increased poliovirus yield, and inhibition of the autophagosomal pathway by 3-methyladenine or by RNA interference against mRNAs that encode two different proteins known to be required for autophagy decreased poliovirus yield. We propose that, for poliovirus and rhinovirus, components of the cellular machinery of autophagosome formation are subverted to promote viral replication. Although autophagy can serve in the innate immune response to microorganisms, our findings are inconsistent with a role for the induced autophagosome-like structures in clearance of poliovirus. Instead, we argue that these double-membraned structures provide membranous supports for viral RNA replication complexes, possibly enabling the nonlytic release of cytoplasmic contents, including progeny virions, from infected cells.",2005 May 26,"['Jackson, William T', 'Giddings, Thomas H', 'Taylor, Matthew P', 'Mulinyawe, Sara', 'Rabinovitch, Marlene', 'Kopito, Ron R', 'Kirkegaard, Karla']",PLoS Biol,,,True
d619c3ceec4db4f3f350c3d5fb3842bd83f04a80,PMC,The immediate effects of the severe acute respiratory syndrome (SARS) epidemic on childbirth in Taiwan,http://dx.doi.org/10.1186/1471-2458-5-30,PMC1084353,15804368,CC BY,"BACKGROUND: When an emerging infectious disease like severe acute respiratory syndrome (SARS) strikes suddenly, many wonder the public's overwhelming fears of SARS may deterred patients from seeking routine care from hospitals and/or interrupt patient's continuity of care. In this study, we sought to estimate the influence of pregnant women's fears of severe acute respiratory syndrome (SARS) on their choice of provider, mode of childbirth, and length of stay (LOS) for the delivery during and after the SARS epidemic in Taiwan. METHODS: The National Health Insurance data from January 01, 2002 to December 31, 2003 were used. A population-based descriptive analysis was conducted to assess the changes in volume, market share, cesarean rate, and average LOS for each of the 4 provider levels, before, during and after the SARS epidemic. RESULTS: Compared to the pre-SARS period, medical centers and regional hospitals dropped 5.2% and 4.1% in market share for childbirth services during the peak SARS period, while district hospitals and clinics increased 2.1% and 7.1%, respectively. For changes in cesarean rates, only a significantly larger increase was observed in medical centers (2.2%) during the peak SARS period. In terms of LOS, significant reductions in average LOS were observed in all hospital levels except for clinics. Average LOS was shortened by 0.21 days in medical centers (5.6%), 0.21 days in regional hospitals (5.8%), and 0.13 days in district hospitals (3.8%). CONCLUSION: The large amount of patients shifting from the maternity wards of more advanced hospitals to those of less advanced hospitals, coupled with the substantial reduction in their length of maternity stay due to their fears of SARS could also lead to serious concerns for quality of care, especially regarding a patient's accessibility to quality providers and continuity of care.",2005 Apr 4,"['Lee, Cheng-Hua', 'Huang, Nicole', 'Chang, Hong-Jen', 'Hsu, Yea-Jen', 'Wang, Mei-Chu', 'Chou, Yiing-Jenq']",BMC Public Health,,,True
d0c6b0c2d387baae89eb2898969913218b3bedff,PMC,Molecular advances in the cell biology of SARS-CoV and current disease prevention strategies,http://dx.doi.org/10.1186/1743-422X-2-35,PMC1087510,15833113,CC BY,"In the aftermath of the SARS epidemic, there has been significant progress in understanding the molecular and cell biology of SARS-CoV. Some of the milestones are the availability of viral genome sequence, identification of the viral receptor, development of an infectious cDNA clone, and the identification of viral antigens that elicit neutralizing antibodies. However, there is still a large gap in our understanding of how SARS-CoV interacts with the host cell and the rapidly changing viral genome adds another variable to this equation. Now the SARS-CoV story has entered a new phase, a search for preventive strategies and a cure for the disease. This review highlights the progress made in identifying molecular aspects of SARS-CoV biology that is relevant in developing disease prevention strategies. Authors conclude that development of successful SARS-CoV vaccines and antivirals depends on the progress we make in these areas in the immediate future.",2005 Apr 15,"['Stark, Caren J', 'Atreya, CD']",Virol J,,,True
e6184d2db86268ba31e49b03a5aab475d5ce5ca6,PMC,Individual sequences in large sets of gene sequences may be distinguished efficiently by combinations of shared sub-sequences,http://dx.doi.org/10.1186/1471-2105-6-90,PMC1090557,15817134,CC BY,"BACKGROUND: Most current DNA diagnostic tests for identifying organisms use specific oligonucleotide probes that are complementary in sequence to, and hence only hybridise with the DNA of one target species. By contrast, in traditional taxonomy, specimens are usually identified by 'dichotomous keys' that use combinations of characters shared by different members of the target set. Using one specific character for each target is the least efficient strategy for identification. Using combinations of shared bisectionally-distributed characters is much more efficient, and this strategy is most efficient when they separate the targets in a progressively binary way. RESULTS: We have developed a practical method for finding minimal sets of sub-sequences that identify individual sequences, and could be targeted by combinations of probes, so that the efficient strategy of traditional taxonomic identification could be used in DNA diagnosis. The sizes of minimal sub-sequence sets depended mostly on sequence diversity and sub-sequence length and interactions between these parameters. We found that 201 distinct cytochrome oxidase subunit-1 (CO1) genes from moths (Lepidoptera) were distinguished using only 15 sub-sequences 20 nucleotides long, whereas only 8–10 sub-sequences 6–10 nucleotides long were required to distinguish the CO1 genes of 92 species from the 9 largest orders of insects. CONCLUSION: The presence/absence of sub-sequences in a set of gene sequences can be used like the questions in a traditional dichotomous taxonomic key; hybridisation probes complementary to such sub-sequences should provide a very efficient means for identifying individual species, subtypes or genotypes. Sequence diversity and sub-sequence length are the major factors that determine the numbers of distinguishing sub-sequences in any set of sequences.",2005 Apr 8,"['Gibbs, Mark J', 'Armstrong, John S', 'Gibbs, Adrian J']",BMC Bioinformatics,,,True
c6008b68c8b16e3a6a48a2cb892bac5c9353df86,PMC,Absence of association between angiotensin converting enzyme polymorphism and development of adult respiratory distress syndrome in patients with severe acute respiratory syndrome: a case control study,http://dx.doi.org/10.1186/1471-2334-5-26,PMC1090578,15819995,CC BY,"BACKGROUND: It has been postulated that genetic predisposition may influence the susceptibility to SARS-coronavirus infection and disease outcomes. A recent study has suggested that the deletion allele (D allele) of the angiotensin converting enzyme (ACE) gene is associated with hypoxemia in SARS patients. Moreover, the ACE D allele has been shown to be more prevalent in patients suffering from adult respiratory distress syndrome (ARDS) in a previous study. Thus, we have investigated the association between ACE insertion/deletion (I/D) polymorphism and the progression to ARDS or requirement of intensive care in SARS patients. METHOD: One hundred and forty genetically unrelated Chinese SARS patients and 326 healthy volunteers were recruited. The ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis. RESULTS: There is no significant difference in the genotypic distributions and the allelic frequencies of the ACE I/D polymorphism between the SARS patients and the healthy control subjects. Moreover, there is also no evidence that ACE I/D polymorphism is associated with the progression to ARDS or the requirement of intensive care in the SARS patients. In multivariate logistic analysis, age is the only factor associated with the development of ARDS while age and male sex are independent factors associated with the requirement of intensive care. CONCLUSION: The ACE I/D polymorphism is not directly related to increased susceptibility to SARS-coronavirus infection and is not associated with poor outcomes after SARS-coronavirus infection.",2005 Apr 9,"['Chan, KC Allen', 'Tang, Nelson LS', 'Hui, David SC', 'Chung, Grace TY', 'Wu, Alan KL', 'Chim, Stephen SC', 'Chiu, Rossa WK', 'Lee, Nelson', 'Choi, KW', 'Sung, YM', 'Chan, Paul KS', 'Tong, YK', 'Lai, ST', 'Yu, WC', 'Tsang, Owen', 'Lo, YM Dennis']",BMC Infect Dis,,,True
6f07f87e8ef78f0416556e69c88247e588f9192c,PMC,A Three-Stemmed mRNA Pseudoknot in the SARS Coronavirus Frameshift Signal,http://dx.doi.org/10.1371/journal.pbio.0030172,PMC1110908,15884978,CC BY,"A wide range of RNA viruses use programmed −1 ribosomal frameshifting for the production of viral fusion proteins. Inspection of the overlap regions between ORF1a and ORF1b of the SARS-CoV genome revealed that, similar to all coronaviruses, a programmed −1 ribosomal frameshift could be used by the virus to produce a fusion protein. Computational analyses of the frameshift signal predicted the presence of an mRNA pseudoknot containing three double-stranded RNA stem structures rather than two. Phylogenetic analyses showed the conservation of potential three-stemmed pseudoknots in the frameshift signals of all other coronaviruses in the GenBank database. Though the presence of the three-stemmed structure is supported by nuclease mapping and two-dimensional nuclear magnetic resonance studies, our findings suggest that interactions between the stem structures may result in local distortions in the A-form RNA. These distortions are particularly evident in the vicinity of predicted A-bulges in stems 2 and 3. In vitro and in vivo frameshifting assays showed that the SARS-CoV frameshift signal is functionally similar to other viral frameshift signals: it promotes efficient frameshifting in all of the standard assay systems, and it is sensitive to a drug and a genetic mutation that are known to affect frameshifting efficiency of a yeast virus. Mutagenesis studies reveal that both the specific sequences and structures of stems 2 and 3 are important for efficient frameshifting. We have identified a new RNA structural motif that is capable of promoting efficient programmed ribosomal frameshifting. The high degree of conservation of three-stemmed mRNA pseudoknot structures among the coronaviruses suggests that this presents a novel target for antiviral therapeutics.",2005 Jun 17,"['Plant, Ewan P', 'Pérez-Alvarado, Gabriela C', 'Jacobs, Jonathan L', 'Mukhopadhyay, Bani', 'Hennig, Mirko', 'Dinman, Jonathan D']",PLoS Biol,,,True
99b74061d99f96f6842cf3efea27058d680ed188,PMC,New Frameshifting Pseudoknot Found in SARS Virus,http://dx.doi.org/10.1371/journal.pbio.0030199,PMC1110910,,CC BY,,2005 Jun 17,,PLoS Biol,,,False
9ffde004c991e9cf3c63e9143946a64ffaa9ee2a,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,True
02b715cc786b21f3e45f79afe877f1c02e9bfd08,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
cdcdd72d94ba5194a20b73cd5332a76f2105df94,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
201de588b3a7dbcf1319dd201fd9ee806f1557d0,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
7178530e60694f264910bd591cc70a707d498bfa,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
8e6d79c06c141e0f13bb4ff2a007ba37b992829e,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
52885ace333b00bb8b096a70aa7f33383f456275,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
01d8f392a96f0b16e1a92bd00b001f82a2507018,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
e875c30d3311bba4f2fc9534c477c61c8d33db84,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
6fc5b537c91bd586409a0a74bde7eb19071467f4,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
fadbf9aa0290ab261722dffc3fb1d6fd486ce0a7,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
c6c8b82bc5a800425b075540eff41b0af719f80f,PMC,HIV Epidemiology in Africa: Weak Variables and Tendentiousness Generate Wobbly Conclusions,http://dx.doi.org/10.1371/journal.pmed.0020137,PMC1140948,15916469,CC BY,,2005 May 31,"['Brody, Stuart', 'Potterat, John J']",PLoS Med,,,True
914c8d326beaccabd37199a9903b27fa7f9b0586,PMC,Pseudoknots: RNA Structures with Diverse Functions,http://dx.doi.org/10.1371/journal.pbio.0030213,PMC1149493,15941360,CC BY,"Just as proteins form distinct structural motifs, certain structures are commonly adopted by RNA molecules. Amongst the most prevalent is the RNA pseudoknot.",2005 Jun 14,"['Staple, David W', 'Butcher, Samuel E']",PLoS Biol,,,True
198ed53d956a2707716d175cc6516bb720f52d82,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,True
3c4e7b941e30be5bcd8c5222305bb53b5374f70c,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,False
c74cbed3524e1dd5d93d9db9d71c9f91ba8561e0,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,False
9c86de3d1107dd2c0fb8d9bb03fff120c41d6559,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,False
283fd3dad298787130f03473882a3dbf22420dc4,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,False
ce545fcd547a3bf435499dd84b5c87332a5c5879,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,False
5baa1fa52d730151424cc2a70242c7937016b815,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,False
c163182040644bbb1350c3d3acacacc431fb07aa,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,False
93f5284236b5257175bfff402f8b8ea90e0a79c0,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,False
68b905ee32b8aad54ae9006fc7aab007c63e9895,PMC,Software for optimization of SNP and PCR-RFLP genotyping to discriminate many genomes with the fewest assays,http://dx.doi.org/10.1186/1471-2164-6-73,PMC1156889,15904493,CC BY,"BACKGROUND: Microbial forensics is important in tracking the source of a pathogen, whether the disease is a naturally occurring outbreak or part of a criminal investigation. RESULTS: A method and SPR Opt (SNP and PCR-RFLP Optimization) software to perform a comprehensive, whole-genome analysis to forensically discriminate multiple sequences is presented. Tools for the optimization of forensic typing using Single Nucleotide Polymorphism (SNP) and PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) analyses across multiple isolate sequences of a species are described. The PCR-RFLP analysis includes prediction and selection of optimal primers and restriction enzymes to enable maximum isolate discrimination based on sequence information. SPR Opt calculates all SNP or PCR-RFLP variations present in the sequences, groups them into haplotypes according to their co-segregation across those sequences, and performs combinatoric analyses to determine which sets of haplotypes provide maximal discrimination among all the input sequences. Those set combinations requiring that membership in the fewest haplotypes be queried (i.e. the fewest assays be performed) are found. These analyses highlight variable regions based on existing sequence data. These markers may be heterogeneous among unsequenced isolates as well, and thus may be useful for characterizing the relationships among unsequenced as well as sequenced isolates. The predictions are multi-locus. Analyses of mumps and SARS viruses are summarized. Phylogenetic trees created based on SNPs, PCR-RFLPs, and full genomes are compared for SARS virus, illustrating that purported phylogenies based only on SNP or PCR-RFLP variations do not match those based on multiple sequence alignment of the full genomes. CONCLUSION: This is the first software to optimize the selection of forensic markers to maximize information gained from the fewest assays, accepting whole or partial genome sequence data as input. As more sequence data becomes available for multiple strains and isolates of a species, automated, computational approaches such as those described here will be essential to make sense of large amounts of information, and to guide and optimize efforts in the laboratory. The software and source code for SPR Opt is publicly available and free for non-profit use at .",2005 May 16,"['Gardner, Shea N', 'Wagner, Mark C']",BMC Genomics,,,True
77aae7c898acfb4ff723de2af7928a38b169878a,PMC,CXCR2 is critical for dsRNA-induced lung injury: relevance to viral lung infection,http://dx.doi.org/10.1186/1476-9255-2-4,PMC1156932,15921526,CC BY,"BACKGROUND: Respiratory viral infections are characterized by the infiltration of leukocytes, including activated neutrophils into the lung that can lead to sustained lung injury and potentially contribute to chronic lung disease. Specific mechanisms recruiting neutrophils to the lung during virus-induced lung inflammation and injury have not been fully elucidated. Since CXCL1 and CXCL2/3, acting through CXCR2, are potent neutrophil chemoattractants, we investigated their role in dsRNA-induced lung injury, where dsRNA (Poly IC) is a well-described synthetic agent mimicking acute viral infection. METHODS: We used 6–8 week old female BALB/c mice to intratracheally inject either single-stranded (ssRNA) or double-stranded RNA (dsRNA) into the airways. The lungs were then harvested at designated timepoints to characterize the elicited chemokine response and resultant lung injury following dsRNA exposure as demonstrated qualititatively by histopathologic analysis, and quantitatively by FACS, protein, and mRNA analysis of BAL fluid and tissue samples. We then repeated the experiments by first pretreating mice with an anti-PMN or corresponding control antibody, and then subsequently pretreating a separate cohort of mice with an anti-CXCR2 or corresponding control antibody prior to dsRNA exposure. RESULTS: Intratracheal dsRNA led to significant increases in neutrophil infiltration and lung injury in BALB/c mice at 72 h following dsRNA, but not in response to ssRNA (Poly C; control) treatment. Expression of CXCR2 ligands and CXCR2 paralleled neutrophil recruitment to the lung. Neutrophil depletion studies significantly reduced neutrophil infiltration and lung injury in response to dsRNA when mice were pretreated with an anti-PMN monoclonal Ab. Furthermore, inhibition of CXCR2 ligands/CXCR2 interaction by pretreating dsRNA-exposed mice with an anti-CXCR2 neutralizing Ab also significantly attenuated neutrophil sequestration and lung injury. CONCLUSION: These findings demonstrate that CXC chemokine ligand/CXCR2 biological axis is critical during the pathogenesis of dsRNA-induced lung injury relevant to acute viral infections.",2005 May 28,"['Londhe, Vedang A', 'Belperio, John A', 'Keane, Michael P', 'Burdick, Marie D', 'Xue, Ying Ying', 'Strieter, Robert M']",J Inflamm (Lond),,,True
4ae8479c3cef7cc97b7edb7cb3e9f86ec51d140e,PMC,Persistence of lung inflammation and lung cytokines with high-resolution CT abnormalities during recovery from SARS,http://dx.doi.org/10.1186/1465-9921-6-42,PMC1156954,15888207,CC BY,"BACKGROUND: During the acute phase of severe acute respiratory syndrome (SARS), mononuclear cells infiltration, alveolar cell desquamation and hyaline membrane formation have been described, together with dysregulation of plasma cytokine levels. Persistent high-resolution computed tomography (HRCT) abnormalities occur in SARS patients up to 40 days after recovery. METHODS: To determine further the time course of recovery of lung inflammation, we investigated the HRCT and inflammatory profiles, and coronavirus persistence in bronchoalveolar lavage fluid (BALF) of 12 patients at recovery at 60 and 90 days. RESULTS: At 60 days, compared to normal controls, SARS patients had increased cellularity of BALF with increased alveolar macrophages (AM) and CD8 cells. HRCT scores were increased and correlated with T-cell numbers and their subpopulations, and inversely with CD4/CD8 ratio. TNF-α, IL-6, IL-8, RANTES and MCP-1 levels were increased. Viral particles in AM were detected by electron microscopy in 7 of 12 SARS patients with high HRCT score. On day 90, HRCT scores improved significantly in 10 of 12 patients, with normalization of BALF cell counts in 6 of 12 patients with repeat bronchoscopy. Pulse steroid therapy and prolonged fever were two independent factors associated with delayed resolution of pneumonitis, in this non-randomized, retrospective analysis. CONCLUSION: Resolution of pneumonitis is delayed in some patients during SARS recovery and may be associated with delayed clearance of coronavirus, Complete resolution may occur by 90 days or later.",2005 May 11,"['Wang, Chun-Hua', 'Liu, Chien-Ying', 'Wan, Yung-Liang', 'Chou, Chun-Liang', 'Huang, Kuo-Hsiung', 'Lin, Horng-Chyuan', 'Lin, Shu-Min', 'Lin, Tzou-Yien', 'Chung, Kian Fan', 'Kuo, Han-Pin']",Respir Res,,,True
eddc547cbba693715e4fd55e6a946e8ec7d96bc2,PMC,A Severe Acute Respiratory Syndrome extranet: supporting local communication and information dissemination,http://dx.doi.org/10.1186/1472-6947-5-17,PMC1166558,15967040,CC BY,"BACKGROUND: The objective of this study was to explore the use and perceptions of a local Severe Acute Respiratory Syndrome (SARS) Extranet and its potential to support future information and communication applications. The SARS Extranet was a single, managed electronic and limited access system to manage local, provincial and other SARS control information. METHODS: During July, 2003, a web-based and paper-based survey was conducted with 53 SARS Steering Committee members in Hamilton. It assessed the use and perceptions of the Extranet that had been built to support the committee during the SARS outbreak. Before distribution, the survey was user-tested based on a think-aloud protocol, and revisions were made. Quantitative and qualitative questions were asked related to frequency of use of the Extranet, perceived overall usefulness of the resource, rationale for use, potential barriers, strengths and limitations, and potential future uses of the Extranet. RESULTS: The response rate was 69.4% (n = 34). Of all respondents, 30 (88.2%) reported that they had visited the site, and rated it highly overall (mean = 4.0; 1 = low to 5 = high). However, the site was rated 3.4 compared with other communications strategies used during the outbreak. Almost half of all respondents (44.1%) visited the site at least once every few days. The two most common reasons the 30 respondents visited the Extranet were to access SARS Steering Committee minutes (63.3%) and to access Hamilton medical advisories (53.3%). The most commonly cited potential future uses for the Extranet were the sending of private emails to public health experts (63.3%), and surveillance (63.3%). No one encountered personal barriers in his or her use of the site, but several mentioned that time and duplication of email information were challenges. CONCLUSION: Despite higher rankings of various communication strategies during the SARS outbreak, such as email, meetings, teleconferences, and other web sites, users generally perceived a local Extranet as a useful support for the dissemination of local information during public health emergencies.",2005 Jun 20,"['Valaitis, Ruta K', 'Akhtar-Danesh, Noori', 'Kealey, Cathy M', 'Brunetti, Glenn M', 'Thomas, Helen']",BMC Med Inform Decis Mak,,,True
6d7084462a7462edc93ce2d350bf6dd08c232ef4,PMC,Peptide inhibitors of dengue virus and West Nile virus infectivity,http://dx.doi.org/10.1186/1743-422X-2-49,PMC1177995,15927084,CC BY,"Viral fusion proteins mediate cell entry by undergoing a series of conformational changes that result in virion-target cell membrane fusion. Class I viral fusion proteins, such as those encoded by influenza virus and human immunodeficiency virus (HIV), contain two prominent alpha helices. Peptides that mimic portions of these alpha helices inhibit structural rearrangements of the fusion proteins and prevent viral infection. The envelope glycoprotein (E) of flaviviruses, such as West Nile virus (WNV) and dengue virus (DENV), are class II viral fusion proteins comprised predominantly of beta sheets. We used a physio-chemical algorithm, the Wimley-White interfacial hydrophobicity scale (WWIHS) [1] in combination with known structural data to identify potential peptide inhibitors of WNV and DENV infectivity that target the viral E protein. Viral inhibition assays confirm that several of these peptides specifically interfere with target virus entry with 50% inhibitory concentration (IC50) in the 10 μM range. Inhibitory peptides similar in sequence to domains with a significant WWIHS scores, including domain II (IIb), and the stem domain, were detected. DN59, a peptide corresponding to the stem domain of DENV, inhibited infection by DENV (>99% inhibition of plaque formation at a concentrations of <25 μM) and cross-inhibition of WNV fusion/infectivity (>99% inhibition at <25 μM) was also demonstrated with DN59. However, a potent WNV inhibitory peptide, WN83, which corresponds to WNV E domain IIb, did not inhibit infectivity by DENV. Additional results suggest that these inhibitory peptides are noncytotoxic and act in a sequence specific manner. The inhibitory peptides identified here can serve as lead compounds for the development of peptide drugs for flavivirus infection.",2005 Jun 1,"['Hrobowski, Yancey M', 'Garry, Robert F', 'Michael, Scott F']",Virol J,,,True
04603867552ffafcaeff68fe8bf7f190ebb08a78,PMC,Appropriate Models for the Management of Infectious Diseases,http://dx.doi.org/10.1371/journal.pmed.0020174,PMC1181873,16013892,CC BY,"BACKGROUND: Mathematical models have become invaluable management tools for epidemiologists, both shedding light on the mechanisms underlying observed dynamics as well as making quantitative predictions on the effectiveness of different control measures. Here, we explain how substantial biases are introduced by two important, yet largely ignored, assumptions at the core of the vast majority of such models. METHODS AND FINDINGS: First, we use analytical methods to show that (i) ignoring the latent period or (ii) making the common assumption of exponentially distributed latent and infectious periods (when including the latent period) always results in underestimating the basic reproductive ratio of an infection from outbreak data. We then proceed to illustrate these points by fitting epidemic models to data from an influenza outbreak. Finally, we document how such unrealistic a priori assumptions concerning model structure give rise to systematically overoptimistic predictions on the outcome of potential management options. CONCLUSION: This work aims to highlight that, when developing models for public health use, we need to pay careful attention to the intrinsic assumptions embedded within classical frameworks.",2005 Jul 26,"['Wearing, Helen J', 'Rohani, Pejman', 'Keeling, Matt J']",PLoS Med,,,True
dd74c8f2961dc716ec9d0c412206c88e0cb9b314,PMC,Information theory-based algorithm for in silico prediction of PCR products with whole genomic sequences as templates,http://dx.doi.org/10.1186/1471-2105-6-190,PMC1183192,16042814,CC BY,"BACKGROUND: A new algorithm for assessing similarity between primer and template has been developed based on the hypothesis that annealing of primer to template is an information transfer process. RESULTS: Primer sequence is converted to a vector of the full potential hydrogen numbers (3 for G or C, 2 for A or T), while template sequence is converted to a vector of the actual hydrogen bond numbers formed after primer annealing. The former is considered as source information and the latter destination information. An information coefficient is calculated as a measure for fidelity of this information transfer process and thus a measure of similarity between primer and potential annealing site on template. CONCLUSION: Successful prediction of PCR products from whole genomic sequences with a computer program based on the algorithm demonstrated the potential of this new algorithm in areas like in silico PCR and gene finding.",2005 Jul 26,"['Cao, Youfang', 'Wang, Lianjie', 'Xu, Kexue', 'Kou, Chunhai', 'Zhang, Yulei', 'Wei, Guifang', 'He, Junjian', 'Wang, Yunfang', 'Zhao, Liping']",BMC Bioinformatics,,,True
a2fedab38bf51ed90c37c61d4f84838c56e5f18a,PMC,Genetic lesions within the 3a gene of SARS-CoV,http://dx.doi.org/10.1186/1743-422X-2-51,PMC1183252,15963240,CC BY,A series of frameshift mutations within the 3a gene has been observed in culture-derived severe acute respiratory syndrome coronavirus (SARS-CoV). We report here that viral RNA from clinical samples obtained from SARS-CoV infected patients also contains a heterogeneous population of wild-type and mutant 3a transcripts.,2005 Jun 20,"['Tan, Timothy HP', 'Barkham, Timothy', 'Fielding, Burtram C', 'Chou, Chih-Fong', 'Shen, Shuo', 'Lim, Seng Gee', 'Hong, Wanjin', 'Tan, Yee-Joo']",Virol J,,,True
0e68ed59a0acf6df0c5ce5a4716b907367fed3f0,PMC,Conservation of pregnancy-specific glycoprotein (PSG) N domains following independent expansions of the gene families in rodents and primates,http://dx.doi.org/10.1186/1471-2148-5-39,PMC1185527,15987510,CC BY,"BACKGROUND: Rodent and primate pregnancy-specific glycoprotein (PSG) gene families have expanded independently from a common ancestor and are expressed virtually exclusively in placental trophoblasts. However, within each species, it is unknown whether multiple paralogs have been selected for diversification of function, or for increased dosage of monofunctional PSG. We analysed the evolution of the mouse PSG sequences, and compared them to rat, human and baboon PSGs to attempt to understand the evolution of this complex gene family. RESULTS: Phylogenetic tree analyses indicate that the primate N domains and the rodent N1 domains exhibit a higher degree of conservation than that observed in a comparison of the mouse N1 and N2 domains, or mouse N1 and N3 domains. Compared to human and baboon PSG N domain exons, mouse and rat PSG N domain exons have undergone less sequence homogenisation. The high non-synonymous substitution rates observed in the CFG face of the mouse N1 domain, within a context of overall conservation, suggests divergence of function of mouse PSGs. The rat PSG family appears to have undergone less expansion than the mouse, exhibits lower divergence rates and increased sequence homogenisation in the CFG face of the N1 domain. In contrast to most primate PSG N domains, rodent PSG N1 domains do not contain an RGD tri-peptide motif, but do contain RGD-like sequences, which are not conserved in rodent N2 and N3 domains. CONCLUSION: Relative conservation of primate N domains and rodent N1 domains suggests that, despite independent gene family expansions and structural diversification, mouse and human PSGs retain conserved functions. Human PSG gene family expansion and homogenisation suggests that evolution occurred in a concerted manner that maintains similar functions of PSGs, whilst increasing gene dosage of the family as a whole. In the mouse, gene family expansion, coupled with local diversification of the CFG face, suggests selection both for increased gene dosage and diversification of function. Partial conservation of RGD and RGD-like tri-peptides in primate and rodent N and N1 domains, respectively, supports a role for these motifs in PSG function.",2005 Jun 29,"['McLellan, Andrew S', 'Zimmermann, Wolfgang', 'Moore, Tom']",BMC Evol Biol,,,True
10e691d6bf9cfc219bb72a2761d37ae5f1677f77,PMC,Croup Is Associated with the Novel Coronavirus NL63,http://dx.doi.org/10.1371/journal.pmed.0020240,PMC1188248,16104827,CC BY,"BACKGROUND: The clinical relevance of infections with the novel human coronavirus NL63 (HCoV-NL63) has not been investigated systematically. We therefore determined its association with disease in young children with lower respiratory tract infection (LRTI). METHODS AND FINDINGS: Nine hundred forty-nine samples of nasopharyngeal secretions from children under 3 y of age with LRTIs were analysed by a quantitative HCoV-NL63-specific real-time PCR. The samples had been collected from hospitalised patients and outpatients from December 1999 to October 2001 in four different regions in Germany as part of the prospective population-based PRI.DE study and analysed for RNA from respiratory viruses. Forty-nine samples (5.2%), mainly derived from the winter season, were positive for HCoV-NL63 RNA. The viral RNA was more prevalent in samples from outpatients (7.9%) than from hospitalised patients (3.2%, p = 0.003), and co-infection with either respiratory syncytial virus or parainfluenza virus 3 was observed frequently. Samples in which only HCoV-NL63 RNA could be detected had a significantly higher viral load than samples containing additional respiratory viruses (median 2.1 × 10(6) versus 2.7 × 10(2) copies/ml, p = 0.0006). A strong association with croup was apparent: 43% of the HCoV-NL63-positive patients with high HCoV-NL63 load and absence of co-infection suffered from croup, compared to 6% in the HCoV-NL63-negative group, p < 0.0001. A significantly higher fraction (17.4%) of samples from croup patients than from non-croup patients (4.2%) contained HCoV-NL63 RNA. CONCLUSION: HCoV-NL63 infections occur frequently in young children with LRTI and show a strong association with croup, suggesting a causal relationship.",2005 Aug 23,"['van der Hoek, Lia', 'Sure, Klaus', 'Ihorst, Gabriele', 'Stang, Alexander', 'Pyrc, Krzysztof', 'Jebbink, Maarten F', 'Petersen, Gudula', 'Forster, Johannes', 'Berkhout, Ben', 'Überla, Klaus']",PLoS Med,,,True
53d23d22eded7c3e0487ceeebaecb43329ba7396,PMC,A Novel Virus for Croup,http://dx.doi.org/10.1371/journal.pmed.0020274,PMC1188251,,CC0,,2005 Aug 23,,PLoS Med,,,False
30e4b834f1684fcc9ba26d41316a44b90aa287a6,PMC,G0/G1 arrest and apoptosis induced by SARS-CoV 3b protein in transfected cells,http://dx.doi.org/10.1186/1743-422X-2-66,PMC1190220,16107218,CC BY,"Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), cause of the life-threatening atypical pneumonia, infects many organs, such as lung, liver and immune organ, and induces parenchyma cells apoptosis and necrosis. The genome of SARS-CoV, not closely related to any of the previously characterized coronavirus, encodes replicase and four major structural proteins and a number of non-structural proteins. Published studies suggest that some non-structural proteins may play important roles in the replication, virulence and pathogenesis of viruses. Among the potential SARS-CoV non-structural proteins, 3b protein (ORF4) is predicted encoding 154 amino acids, lacking significant similarities to any known proteins. Till now, there is no report about the function of 3b protein. In this study, 3b gene was linked with the EGFP tag at the C- terminus. Through cell cycle analysis, it was found that over-expression of 3b-EGFP protein in Vero, 293 and COS-7 cells could induce cell cycle arrest at G0/G1 phase, and that especially in COS-7 cells, expression of 3b-EGFP was able to induce the increase of sub-G1 phase from 24 h after transfection, which was most obvious at 48 h. The apoptosis induction of 3b fusion protein in COS-7 cells was further confirmed by double cell labeling with 7-AAD and Annexin V, the function of 3b protein inducing cell G0/G1 arrest and apoptosis may provide a new insight for further study on the mechanism of SARS pathogenesis.",2005 Aug 17,"['Yuan, Xiaoling', 'Shan, Yajun', 'Zhao, Zhenhu', 'Chen, Jiapei', 'Cong, Yuwen']",Virol J,,,True
bd92cbae7179f07d59d1ce4d7ca96e37ebb40ec9,PMC,Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030324,PMC1197287,16128623,CC BY,"The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.",2005 Oct 6,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,True
752693d2137be042f6d7e42e1aa034f5bfb95d9f,PMC,Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030324,PMC1197287,16128623,CC BY,"The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.",2005 Oct 6,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,True
7f51cd332e57025cff78572e683429428664cf49,PMC,Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030324,PMC1197287,16128623,CC BY,"The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.",2005 Oct 6,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,False
d8591102a5fb4a6ca07cd30418f80c913bb1000d,PMC,Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030324,PMC1197287,16128623,CC BY,"The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.",2005 Oct 6,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,False
08a23c9d22d75baf28efcfd7aee03fdc8ed65058,PMC,Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030324,PMC1197287,16128623,CC BY,"The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.",2005 Oct 6,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,False
a44f72e913b445c399d966da1406ff8af979a229,PMC,Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030324,PMC1197287,16128623,CC BY,"The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.",2005 Oct 6,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,False
907ae5d1ab217c06925ef5cb0fbbf566ac06c5c7,PMC,Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030324,PMC1197287,16128623,CC BY,"The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.",2005 Oct 6,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,False
7b52146058cfa616d16f1d86ff502bc235175fd3,PMC,Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030324,PMC1197287,16128623,CC BY,"The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.",2005 Oct 6,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,False
a9b8e1cd354483fc8d7825a2ba27d4e7c16c56ce,PMC,Casting a Wide Net to Fight Coronaviruses,http://dx.doi.org/10.1371/journal.pbio.0030353,PMC1197291,,CC BY,,2005 Oct 6,,PLoS Biol,,,False
0450e1d435d63e69e1867c2eba65c0c08af70038,PMC,Phosphatidylserine treatment relieves the block to retrovirus infection of cells expressing glycosylated virus receptors,http://dx.doi.org/10.1186/1742-4690-2-49,PMC1201173,16091143,CC BY,"BACKGROUND: A major determinant of retrovirus host range is the presence or absence of appropriate cell-surface receptors required for virus entry. Often orthologs of functional receptors are present in a wide range of species, but amino acid differences can render these receptors non-functional. In some cases amino acid differences result in additional N-linked glycosylation that blocks virus infection. The latter block to retrovirus infection can be overcome by treatment of cells with compounds such as tunicamycin, which prevent the addition of N-linked oligosaccharides. RESULTS: We have discovered that treatment of cells with liposomes composed of phosphatidylserine (PS) can also overcome the block to infection mediated by N-linked glycosylation. Importantly, this effect occurs without apparent change in the glycosylation state of the receptors for these viruses. This effect occurs with delayed kinetics compared to previous results showing enhancement of virus infection by PS treatment of cells expressing functional virus receptors. CONCLUSION: We have demonstrated that PS treatment can relieve the block to retrovirus infection of cells expressing retroviral receptors that have been rendered non-functional by glycosylation. These findings have important implications for the current model describing inhibition of virus entry by receptor glycosylation.",2005 Aug 9,"['Coil, David A', 'Miller, A Dusty']",Retrovirology,,,True
4e1a080ea558bba7654e05d59ed0b6c6e686b66e,PMC,A new paradigm in respiratory hygiene: increasing the cohesivity of airway secretions to improve cough interaction and reduce aerosol dispersion,http://dx.doi.org/10.1186/1471-2466-5-11,PMC1208914,16138926,CC BY,"BACKGROUND: Infectious respiratory diseases are transmitted to non-infected subjects when an infected person expels pathogenic microorganisms to the surrounding environment when coughing or sneezing. When the airway mucus layer interacts with high-speed airflow, droplets are expelled as aerosol; their concentration and size distribution may each play an important role in disease transmission. Our goal is to reduce the aerosolizability of respiratory secretions while interfering only minimally with normal mucus clearance using agents capable of increasing crosslinking in the mucin glycoprotein network. METHODS: We exposed mucus simulants (MS) to airflow in a simulated cough machine (SCM). The MS ranged from non-viscous, non-elastic substances (water) to MS of varying degrees of viscosity and elasticity. Mucociliary clearance of the MS was assessed on the frog palate, elasticity in the Filancemeter and the aerosol pattern in a ""bulls-eye"" target. The sample loaded was weighed before and after each cough maneuver. We tested two mucomodulators: sodium tetraborate (XL""B"") and calcium chloride (XL ""C""). RESULTS: Mucociliary transport was close to normal speed in viscoelastic samples compared to non-elastic, non-viscous or viscous-only samples. Spinnability ranged from 2.5 ± 0.6 to 50.9 ± 6.9 cm, and the amount of MS expelled from the SCM increased from 47 % to 96 % adding 1.5 μL to 150 μL of XL ""B"". Concurrently, particles were inversely reduced to almost disappear from the aerosolization pattern. CONCLUSION: The aerosolizability of MS was modified by increasing its cohesivity, thereby reducing the number of particles expelled from the SCM while interfering minimally with its clearance on the frog palate. An unexpected finding is that MS crosslinking increased ""expectoration"".",2005 Sep 2,"['Zayas, Gustavo', 'Dimitry, John', 'Zayas, Ana', ""O'Brien, Darryl"", 'King, Malcolm']",BMC Pulm Med,,,True
60666795212b915f165db9762a95445be1fb2bad,PMC,The health impacts of globalisation: a conceptual framework,http://dx.doi.org/10.1186/1744-8603-1-14,PMC1208931,16078989,CC BY,"This paper describes a conceptual framework for the health implications of globalisation. The framework is developed by first identifying the main determinants of population health and the main features of the globalisation process. The resulting conceptual model explicitly visualises that globalisation affects the institutional, economic, social-cultural and ecological determinants of population health, and that the globalisation process mainly operates at the contextual level, while influencing health through its more distal and proximal determinants. The developed framework provides valuable insights in how to organise the complexity involved in studying the health effects resulting from globalisation. It could, therefore, give a meaningful contribution to further empirical research by serving as a 'think-model' and provides a basis for the development of future scenarios on health.",2005 Aug 3,"['Huynen, Maud MTE', 'Martens, Pim', 'Hilderink, Henk BM']",Global Health,,,True
d1d7471ec350b7a5839863b90218a6c0b9596e85,PMC,The potential impact of the next influenza pandemic on a national primary care medical workforce,http://dx.doi.org/10.1186/1478-4491-3-7,PMC1215505,16092972,CC BY,"BACKGROUND: Another influenza pandemic is all but inevitable. We estimated its potential impact on the primary care medical workforce in New Zealand, so that planning could mitigate the disruption from the pandemic and similar challenges. METHODS: The model in the ""FluAid"" software (Centers for Disease Control and Prevention, CDC, Atlanta) was applied to the New Zealand primary care medical workforce (i.e., general practitioners). RESULTS: At its peak (week 4) the pandemic would lead to 1.2% to 2.7% loss of medical work time, using conservative baseline assumptions. Most workdays (88%) would be lost due to illness, followed by hospitalisation (8%), and then premature death (4%). Inputs for a ""more severe"" scenario included greater health effects and time spent caring for sick relatives. For this scenario, 9% of medical workdays would be lost in the peak week, and 3% over a more compressed six-week period of the first pandemic wave. As with the base case, most (64%) of lost workdays would be due to illness, followed by caring for others (31%), hospitalisation (4%), and then premature death (1%). CONCLUSION: Preparedness planning for future influenza pandemics must consider the impact on this medical workforce and incorporate strategies to minimise this impact, including infection control measures, well-designed protocols, and improved health sector surge capacity.",2005 Aug 11,"['Wilson, Nick', 'Baker, Michael', 'Crampton, Peter', 'Mansoor, Osman']",Hum Resour Health,,,True
33f0a6576216e3c8ff02dcb1affaa66c9f08e30b,PMC,Macrophages and cytokines in the early defence against herpes simplex virus,http://dx.doi.org/10.1186/1743-422X-2-59,PMC1215526,16076403,CC BY,"Herpes simplex virus (HSV) type 1 and 2 are old viruses, with a history of evolution shared with humans. Thus, it is generally well-adapted viruses, infecting many of us without doing much harm, and with the capacity to hide in our neurons for life. In rare situations, however, the primary infection becomes generalized or involves the brain. Normally, the primary HSV infection is asymptomatic, and a crucial element in the early restriction of virus replication and thus avoidance of symptoms from the infection is the concerted action of different arms of the innate immune response. An early and light struggle inhibiting some HSV replication will spare the host from the real war against huge amounts of virus later in infection. As far as such a war will jeopardize the life of the host, it will be in both interests, including the virus, to settle the conflict amicably. Some important weapons of the unspecific defence and the early strikes and beginning battle during the first days of a HSV infection are discussed in this review. Generally, macrophages are orchestrating a multitude of anti-herpetic actions during the first hours of the attack. In a first wave of responses, cytokines, primarily type I interferons (IFN) and tumour necrosis factor are produced and exert a direct antiviral effect and activate the macrophages themselves. In the next wave, interleukin (IL)-12 together with the above and other cytokines induce production of IFN-γ in mainly NK cells. Many positive feed-back mechanisms and synergistic interactions intensify these systems and give rise to heavy antiviral weapons such as reactive oxygen species and nitric oxide. This results in the generation of an alliance against the viral enemy. However, these heavy weapons have to be controlled to avoid too much harm to the host. By IL-4 and others, these reactions are hampered, but they are still allowed in foci of HSV replication, thus focusing the activity to only relevant sites. So, no hero does it alone. Rather, an alliance of cytokines, macrophages and other cells seems to play a central role. Implications of this for future treatment modalities are shortly considered.",2005 Aug 3,"Ellermann-Eriksen, Svend",Virol J,,,True
7d6a4a17160dee1235864e5860da782093e4d07b,PMC,"Patterns of HIV prevalence among injecting drug users in the cross-border area of Lang Son Province, Vietnam, and Ning Ming County, Guangxi Province, China",http://dx.doi.org/10.1186/1471-2458-5-89,PMC1232855,16120225,CC BY,"BACKGROUND: To assess patterns of injecting drug use and HIV prevalence among injecting drug users (IDUs) in an international border area along a major heroin trans-shipment route. METHODS: Cross-sectional surveys of IDUs in 5 sites in Lang Son Province, Vietnam (n = 348) and 3 sites in Ning Ming County, Guangxi Province, China (n = 308). Respondents were recruited through peer referral (""snowball"") methods in both countries, and also from officially recorded lists of IDUs in Vietnam. A risk behavior questionnaire was administered and HIV counseling and testing conducted. RESULTS: Participants in both countries were largely male, in their 20s, and unmarried. A majority of subjects in both countries were members of ethnic minority groups. There were strong geographic gradients for length of drug injecting and for HIV seroprevalence. Both mean years injecting and HIV seroprevalence declined from the Vietnamese site farthest from the border to the Chinese site farthest from the border. 10.6% of participants in China and 24.5% of participants in Vietnam reported crossing the international border in the 6 months prior to interview. Crossing the border by IDUs was associated with (1) distance from the border, (2) being a member of an ethnic minority group, and (3) being HIV seropositive among Chinese participants. CONCLUSION: Reducing the international spread of HIV among IDUs will require programs at the global, regional, national, and ""local cross border"" levels. At the local cross border level, the programs should be coordinated on both sides of the border and on a sufficient scale that IDUs will be able to readily obtain clean injection equipment on the other side of the border as well as in their country of residence.",2005 Aug 24,"['Des Jarlais, Don C', 'Johnston, Patrick', 'Friedmann, Patricia', 'Kling, Ryan', 'Liu, Wei', 'Ngu, Doan', 'Chen, Yi', 'Hoang, Tran V', 'Donghua, Meng', 'Van, Ly K', 'Tung, Nguyen D', 'Binh, Kieu T', 'Hammett, Theodore M']",BMC Public Health,,,True
a4b16ad01125dda3a5dd4ae97fe8cb53c9538075,PMC,Chloroquine is a potent inhibitor of SARS coronavirus infection and spread,http://dx.doi.org/10.1186/1743-422X-2-69,PMC1232869,16115318,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS) is caused by a newly discovered coronavirus (SARS-CoV). No effective prophylactic or post-exposure therapy is currently available. RESULTS: We report, however, that chloroquine has strong antiviral effects on SARS-CoV infection of primate cells. These inhibitory effects are observed when the cells are treated with the drug either before or after exposure to the virus, suggesting both prophylactic and therapeutic advantage. In addition to the well-known functions of chloroquine such as elevations of endosomal pH, the drug appears to interfere with terminal glycosylation of the cellular receptor, angiotensin-converting enzyme 2. This may negatively influence the virus-receptor binding and abrogate the infection, with further ramifications by the elevation of vesicular pH, resulting in the inhibition of infection and spread of SARS CoV at clinically admissible concentrations. CONCLUSION: Chloroquine is effective in preventing the spread of SARS CoV in cell culture. Favorable inhibition of virus spread was observed when the cells were either treated with chloroquine prior to or after SARS CoV infection. In addition, the indirect immunofluorescence assay described herein represents a simple and rapid method for screening SARS-CoV antiviral compounds.",2005 Aug 22,"['Vincent, Martin J', 'Bergeron, Eric', 'Benjannet, Suzanne', 'Erickson, Bobbie R', 'Rollin, Pierre E', 'Ksiazek, Thomas G', 'Seidah, Nabil G', 'Nichol, Stuart T']",Virol J,,,True
3bd02864e1ab4b40712401ac5a0c8580dc98c0c9,PMC,The SARS Coronavirus S Glycoprotein Receptor Binding Domain: Fine Mapping and Functional Characterization,http://dx.doi.org/10.1186/1743-422X-2-73,PMC1236967,16122388,CC BY,"The entry of the SARS coronavirus (SCV) into cells is initiated by binding of its spike envelope glycoprotein (S) to a receptor, ACE2. We and others identified the receptor-binding domain (RBD) by using S fragments of various lengths but all including the amino acid residue 318 and two other potential glycosylation sites. To further characterize the role of glycosylation and identify residues important for its function as an interacting partner of ACE2, we have cloned, expressed and characterized various soluble fragments of S containing RBD, and mutated all potential glycosylation sites and 32 other residues. The shortest of these fragments still able to bind the receptor ACE2 did not include residue 318 (which is a potential glycosylation site), but started at residue 319, and has only two potential glycosylation sites (residues 330 and 357). Mutation of each of these sites to either alanine or glutamine, as well as mutation of residue 318 to alanine in longer fragments resulted in the same decrease of molecular weight (by approximately 3 kDa) suggesting that all glycosylation sites are functional. Simultaneous mutation of all glycosylation sites resulted in lack of expression suggesting that at least one glycosylation site (any of the three) is required for expression. Glycosylation did not affect binding to ACE2. Alanine scanning mutagenesis of the fragment S319–518 resulted in the identification of ten residues (K390, R426, D429, T431, I455, N473, F483, Q492, Y494, R495) that significantly reduced binding to ACE2, and one residue (D393) that appears to increase binding. Mutation of residue T431 reduced binding by about 2-fold, and mutation of the other eight residues – by more than 10-fold. Analysis of these data and the mapping of these mutations on the recently determined crystal structure of a fragment containing the RBD complexed to ACE2 (Li, F, Li, W, Farzan, M, and Harrison, S. C., submitted) suggested the existence of two hot spots on the S RBD surface, R426 and N473, which are likely to contribute significant portion of the binding energy. The finding that most of the mutations (23 out of 34 including glycosylation sites) do not affect the RBD binding function indicates possible mechanisms for evasion of immune responses.",2005 Aug 25,"['Chakraborti, Samitabh', 'Prabakaran, Ponraj', 'Xiao, Xiaodong', 'Dimitrov, Dimiter S']",Virol J,,,True
c49e3b42331dd3c65340f486f5b6067df16cbbd4,PMC,E-Predict: a computational strategy for species identification based on observed DNA microarray hybridization patterns,http://dx.doi.org/10.1186/gb-2005-6-9-r78,PMC1242213,16168085,CC BY,"DNA microarrays may be used to identify microbial species present in environmental and clinical samples. However, automated tools for reliable species identification based on observed microarray hybridization patterns are lacking. We present an algorithm, E-Predict, for microarray-based species identification. E-Predict compares observed hybridization patterns with theoretical energy profiles representing different species. We demonstrate the application of the algorithm to viral detection in a set of clinical samples and discuss its relevance to other metagenomic applications.",2005 Aug 30,"['Urisman, Anatoly', 'Fischer, Kael F', 'Chiu, Charles Y', 'Kistler, Amy L', 'Beck, Shoshannah', 'Wang, David', 'DeRisi, Joseph L']",Genome Biol,,,True
29d776d7a6f03cf59887534629dcbe5014f09aed,PMC,"Web GIS in practice III: creating a simple interactive map of England's Strategic Health Authorities using Google Maps API, Google Earth KML, and MSN Virtual Earth Map Control",http://dx.doi.org/10.1186/1476-072X-4-22,PMC1242244,16176577,CC BY,"This eye-opener article aims at introducing the health GIS community to the emerging online consumer geoinformatics services from Google and Microsoft (MSN), and their potential utility in creating custom online interactive health maps. Using the programmable interfaces provided by Google and MSN, we created three interactive demonstrator maps of England's Strategic Health Authorities. These can be browsed online at – Google Maps API (Application Programming Interface) version, – Google Earth KML (Keyhole Markup Language) version, and – MSN Virtual Earth Map Control version. Google and MSN's worldwide distribution of ""free"" geospatial tools, imagery, and maps is to be commended as a significant step towards the ultimate ""wikification"" of maps and GIS. A discussion is provided of these emerging online mapping trends, their expected future implications and development directions, and associated individual privacy, national security and copyrights issues. Although ESRI have announced their planned response to Google (and MSN), it remains to be seen how their envisaged plans will materialize and compare to the offerings from Google and MSN, and also how Google and MSN mapping tools will further evolve in the near future.",2005 Sep 21,"Boulos, Maged N Kamel",Int J Health Geogr,,,True
5b3e895eea9402eca728dbe11b00431d4bacbc7f,PMC,The National Children’s Study: A Critical National Investment,,PMC1247577,15471708,CC0,,2004 Oct,"['Trasande, Leonardo', 'Landrigan, Philip J.']",Environ Health Perspect,,,True
a3c3b7c38ad32e1042d78aae2027ca491e9f2197,PMC,Understanding the Spatial Clustering of Severe Acute Respiratory Syndrome (SARS) in Hong Kong,http://dx.doi.org/10.1289/ehp.7117,PMC1247620,15531441,CC0,"We applied cartographic and geostatistical methods in analyzing the patterns of disease spread during the 2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong using geographic information system (GIS) technology. We analyzed an integrated database that contained clinical and personal details on all 1,755 patients confirmed to have SARS from 15 February to 22 June 2003. Elementary mapping of disease occurrences in space and time simultaneously revealed the geographic extent of spread throughout the territory. Statistical surfaces created by the kernel method confirmed that SARS cases were highly clustered and identified distinct disease “hot spots.” Contextual analysis of mean and standard deviation of different density classes indicated that the period from day 1 (18 February) through day 16 (6 March) was the prodrome of the epidemic, whereas days 86 (15 May) to 106 (4 June) marked the declining phase of the outbreak. Origin-and-destination plots showed the directional bias and radius of spread of superspreading events. Integration of GIS technology into routine field epidemiologic surveillance can offer a real-time quantitative method for identifying and tracking the geospatial spread of infectious diseases, as our experience with SARS has demonstrated.",2004 Nov 27,"['Lai, P.C.', 'Wong, C.M.', 'Hedley, A.J.', 'Lo, S.V.', 'Leung, P.Y.', 'Kong, J.', 'Leung, G.M.']",Environ Health Perspect,,,True
87ad4bcfb14f3ae9f7eb1a0642d50fad167349e2,PMC,The Big Picture,,PMC1247652,,CC0,,2004 Nov,"Alderson, Laura",Environ Health Perspect,,,True
5227121ac5523e669cc04c9a8f2660080d995a34,PMC,A combined nucleocapsid vaccine induces vigorous SARS-CD8+ T-cell immune responses,http://dx.doi.org/10.1186/1479-0556-3-7,PMC1249587,16115319,CC BY,"Several studies have shown that cell-mediated immune responses play a crucial role in controlling viral replication. As such, a candidate SARS vaccine should elicit broad CD8+ T-cell immune responses. Several groups of mice were immunized alone or in combination with SARS-nucleocapsid immunogen. A high level of specific SARS-CD8+ T-cell response was demonstrated in mice that received DNA encoding the SARS-nucleocapsid, protein and XIAP as an adjuvant. We also observed that co-administration of a plasmid expressing nucleocapsid, recombinant protein and montanide/CpG induces high antibody titers in immunized mice. Moreover, this vaccine approach merits further investigation as a potential candidate vaccine against SARS.",2005 Aug 22,"['Azizi, Ali', 'Aucoin, Susan', 'Tadesse, Helina', 'Frost, Rita', 'Ghorbani, Masoud', 'Soare, Catalina', 'Naas, Turaya', 'Diaz-Mitoma, Francisco']",Genet Vaccines Ther,,,True
c1c6a98c21304f3788b20870b34afd8a115fa38c,PMC,The Application of the Haddon Matrix to Public Health Readiness and Response Planning,http://dx.doi.org/10.1289/ehp.7491,PMC1257548,15866764,CC0,"State and local health departments continue to face unprecedented challenges in preparing for, recognizing, and responding to threats to the public’s health. The attacks of 11 September 2001 and the ensuing anthrax mailings of 2001 highlighted the public health readiness and response hurdles posed by intentionally caused injury and illness. At the same time, recent natural disasters have highlighted the need for comparable public health readiness and response capabilities. Public health readiness and response activities can be conceptualized similarly for intentional attacks, natural disasters, and human-caused accidents. Consistent with this view, the federal government has adopted the all-hazards response model as its fundamental paradigm. Adoption of this paradigm provides powerful improvements in efficiency and efficacy, because it reduces the need to create a complex family of situation-specific preparedness and response activities. However, in practice, public health preparedness requires additional models and tools to provide a framework to better understand and prioritize emergency readiness and response needs, as well as to facilitate solutions; this is particularly true at the local health department level. Here, we propose to extend the use of the Haddon matrix—a conceptual model used for more than two decades in injury prevention and response strategies—for this purpose.",2005 May 2,"['Barnett, Daniel J.', 'Balicer, Ran D.', 'Blodgett, David', 'Fews, Ayanna L.', 'Parker, Cindy L.', 'Links, Jonathan M.']",Environ Health Perspect,,,True
9b960b5f7c871b2dbb4ee3ba78392ca6a333224b,PMC,"Replicative homeostasis II: Influence of polymerase fidelity on RNA virus quasispecies biology: Implications for immune recognition, viral autoimmunity and other ""virus receptor"" diseases",http://dx.doi.org/10.1186/1743-422X-2-70,PMC1260030,16115320,CC BY,"Much of the worlds' population is in active or imminent danger from established infectious pathogens, while sporadic and pandemic infections by these and emerging agents threaten everyone. RNA polymerases (RNA(pol)) generate enormous genetic and consequent antigenic heterogeneity permitting both viruses and cellular pathogens to evade host defences. Thus, RNA(pol )causes more morbidity and premature mortality than any other molecule. The extraordinary genetic heterogeneity defining viral quasispecies results from RNA(pol )infidelity causing rapid cumulative genomic RNA mutation a process that, if uncontrolled, would cause catastrophic loss of sequence integrity and inexorable quasispecies extinction. Selective replication and replicative homeostasis, an epicyclical regulatory mechanism dynamically linking RNApol fidelity and processivity with quasispecies phenotypic diversity, modulating polymerase fidelity and, hence, controlling quasispecies behaviour, prevents this happening and also mediates immune escape. Perhaps more importantly, ineluctable generation of broad phenotypic diversity after viral RNA is translated to protein quasispecies suggests a mechanism of disease that specifically targets, and functionally disrupts, the host cell surface molecules – including hormone, lipid, cell signalling or neurotransmitter receptors – that viruses co-opt for cell entry. This mechanism – ""Viral Receptor Disease (VRD)"" – may explain so-called ""viral autoimmunity"", some classical autoimmune disorders and other diseases, including type II diabetes mellitus, and some forms of obesity. Viral receptor disease is a unifying hypothesis that may also explain some diseases with well-established, but multi-factorial and apparently unrelated aetiologies – like coronary artery and other vascular diseases – in addition to diseases like schizophrenia that are poorly understood and lack plausible, coherent, pathogenic explanations.",2005 Aug 22,"Sallie, Richard",Virol J,,,True
d6ea8e153027d428bc443df40d70bfa2134a2deb,PMC,Generation of human antibody fragments recognizing distinct epitopes of the nucleocapsid (N) SARS-CoV protein using a phage display approach,http://dx.doi.org/10.1186/1471-2334-5-73,PMC1261265,16171519,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS)-CoV is a newly emerging virus that causes SARS with high mortality rate in infected people. Successful control of the global SARS epidemic will require rapid and sensitive diagnostic tests to monitor its spread, as well as, the development of vaccines and new antiviral compounds including neutralizing antibodies that effectively prevent or treat this disease. METHODS: The human synthetic single-chain fragment variable (scFv) ETH-2 phage antibody library was used for the isolation of scFvs against the nucleocapsid (N) protein of SARS-CoV using a bio panning-based strategy. The selected scFvs were characterized under genetics-molecular aspects and for SARS-CoV N protein detection in ELISA, western blotting and immunocytochemistry. RESULTS: Human scFv antibodies to N protein of SARS-CoV can be easily isolated by selecting the ETH-2 phage library on immunotubes coated with antigen. These in vitro selected human scFvs specifically recognize in ELISA and western blotting studies distinct epitopes in N protein domains and detect in immunohistochemistry investigations SARS-CoV particles in infected Vero cells. CONCLUSION: The human scFv antibodies isolated and described in this study represent useful reagents for rapid detection of N SARS-CoV protein and SARS virus particles in infected target cells.",2005 Sep 19,"['Flego, Michela', 'Di Bonito, Paola', 'Ascione, Alessandro', 'Zamboni, Silvia', 'Carattoli, Alessandra', 'Grasso, Felicia', 'Cassone, Antonio', 'Cianfriglia, Maurizio']",BMC Infect Dis,,,True
79da8c8e26960026682cb2daf09ec3357b1bec5a,PMC,Molecular signature of clinical severity in recovering patients with severe acute respiratory syndrome coronavirus (SARS-CoV),http://dx.doi.org/10.1186/1471-2164-6-132,PMC1262710,16174304,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS), a recent epidemic human disease, is caused by a novel coronavirus (SARS-CoV). First reported in Asia, SARS quickly spread worldwide through international travelling. As of July 2003, the World Health Organization reported a total of 8,437 people afflicted with SARS with a 9.6% mortality rate. Although immunopathological damages may account for the severity of respiratory distress, little is known about how the genome-wide gene expression of the host changes under the attack of SARS-CoV. RESULTS: Based on changes in gene expression of peripheral blood, we identified 52 signature genes that accurately discriminated acute SARS patients from non-SARS controls. While a general suppression of gene expression predominated in SARS-infected blood, several genes including those involved in innate immunity, such as defensins and eosinophil-derived neurotoxin, were upregulated. Instead of employing clustering methods, we ranked the severity of recovering SARS patients by generalized associate plots (GAP) according to the expression profiles of 52 signature genes. Through this method, we discovered a smooth transition pattern of severity from normal controls to acute SARS patients. The rank of SARS severity was significantly correlated with the recovery period (in days) and with the clinical pulmonary infection score. CONCLUSION: The use of the GAP approach has proved useful in analyzing the complexity and continuity of biological systems. The severity rank derived from the global expression profile of significantly regulated genes in patients may be useful for further elucidating the pathophysiology of their disease.",2005 Sep 21,"['Lee, Yun-Shien', 'Chen, Chun-Houh', 'Chao, Angel', 'Chen, En-Shih', 'Wei, Min-Li', 'Chen, Lung-Kun', 'Yang, Kuender D', 'Lin, Meng-Chih', 'Wang, Yi-Hsi', 'Liu, Jien-Wei', 'Eng, Hock-Liew', 'Chiang, Ping-Cherng', 'Wu, Ting-Shu', 'Tsao, Kuo-Chein', 'Huang, Chung-Guei', 'Tien, Yin-Jing', 'Wang, Tzu-Hao', 'Wang, Hsing-Shih', 'Lee, Ying-Shiung']",BMC Genomics,,,True
e6d533faf65d64332697077b71aa71dfc78fc06a,PMC,The effects of injection of bovine vaccine into a human digit: a case report,http://dx.doi.org/10.1186/1476-069X-4-21,PMC1262740,16219096,CC BY,BACKGROUND: The incidence of needlestick injuries in farmers and veterinary surgeons is significant and the consequences of such an injection can be serious. CASE PRESENTATION: We report accidental injection of bovine vaccine into the base of the little finger. This resulted in increased pressure in the flexor sheath causing signs and symptoms of ischemia. Amputation of the digit was required despite repeated surgical debridement and decompression. CONCLUSION: There have been previous reports of injection of oil-based vaccines into the human hand resulting in granulomatous inflammation or sterile abscess and causing morbidity and tissue loss. Self-injection with veterinary vaccines is an occupational hazard for farmers and veterinary surgeons. Injection of vaccine into a closed compartment such as the human finger can have serious sequelae including loss of the injected digit. These injuries are not to be underestimated. Early debridement and irrigation of the injected area with decompression is likely to give the best outcome. Frequent review is necessary after the first procedure because repeat operations may be required.,2005 Oct 11,"[""O'Neill, Jennifer K"", 'Richards, Simon W', 'Ricketts, David M', 'Patterson, Marc H']",Environ Health,,,True
9f63ebfaab049c0968d72166761217b3aaa1fe00,PMC,Pneumothorax and mortality in the mechanically ventilated SARS patients: a prospective clinical study,http://dx.doi.org/10.1186/cc3736,PMC1269458,16137358,CC BY,"INTRODUCTION: Pneumothorax often complicates the management of mechanically ventilated severe acute respiratory syndrome (SARS) patients in the isolation intensive care unit (ICU). We sought to determine whether pneumothoraces are induced by high ventilatory pressure or volume and if they are associated with mortality in mechanically ventilated SARS patients. METHODS: We conducted a prospective, clinical study. Forty-one mechanically ventilated SARS patients were included in our study. All SARS patients were sedated and received mechanical ventilation in the isolation ICU. RESULTS: The mechanically ventilated SARS patients were divided into two groups either with or without pneumothorax. Their demographic data, clinical characteristics, ventilatory variables such as positive end-expiratory pressure, peak inspiratory pressure, mean airway pressure, tidal volume, tidal volume per kilogram, respiratory rate and minute ventilation and the accumulated mortality rate at 30 days after mechanical ventilation were analyzed. There were no statistically significant differences in the pressures and volumes between the two groups, and the mortality was also similar between the groups. However, patients developing pneumothorax during mechanical ventilation frequently expressed higher respiratory rates on admission, and a lower PaO(2)/FiO(2 )ratio and higher PaCO(2 )level during hospitalization compared with those without pneumothorax. CONCLUSION: In our study, the SARS patients who suffered pneumothorax presented as more tachypnic on admission, and more pronounced hypoxemic and hypercapnic during hospitalization. These variables signaled a deterioration in respiratory function and could be indicators of developing pneumothorax during mechanical ventilation in the SARS patients. Meanwhile, meticulous respiratory therapy and monitoring were mandatory in these patients.",2005 Jun 22,"['Kao, Hsin-Kuo', 'Wang, Jia-Horng', 'Sung, Chun-Sung', 'Huang, Ying-Che', 'Lien, Te-Cheng']",Crit Care,,,True
5b13e81ee4495ff3eccaeea21f955ebc5e5cbde1,PMC,Using autoregressive integrated moving average (ARIMA) models to predict and monitor the number of beds occupied during a SARS outbreak in a tertiary hospital in Singapore,http://dx.doi.org/10.1186/1472-6963-5-36,PMC1274243,15885149,CC BY,"BACKGROUND: The main objective of this study is to apply autoregressive integrated moving average (ARIMA) models to make real-time predictions on the number of beds occupied in Tan Tock Seng Hospital, during the recent SARS outbreak. METHODS: This is a retrospective study design. Hospital admission and occupancy data for isolation beds was collected from Tan Tock Seng hospital for the period 14(th )March 2003 to 31(st )May 2003. The main outcome measure was daily number of isolation beds occupied by SARS patients. Among the covariates considered were daily number of people screened, daily number of people admitted (including observation, suspect and probable cases) and days from the most recent significant event discovery. We utilized the following strategy for the analysis. Firstly, we split the outbreak data into two. Data from 14(th )March to 21(st )April 2003 was used for model development. We used structural ARIMA models in an attempt to model the number of beds occupied. Estimation is via the maximum likelihood method using the Kalman filter. For the ARIMA model parameters, we considered the simplest parsimonious lowest order model. RESULTS: We found that the ARIMA (1,0,3) model was able to describe and predict the number of beds occupied during the SARS outbreak well. The mean absolute percentage error (MAPE) for the training set and validation set were 5.7% and 8.6% respectively, which we found was reasonable for use in the hospital setting. Furthermore, the model also provided three-day forecasts of the number of beds required. Total number of admissions and probable cases admitted on the previous day were also found to be independent prognostic factors of bed occupancy. CONCLUSION: ARIMA models provide useful tools for administrators and clinicians in planning for real-time bed capacity during an outbreak of an infectious disease such as SARS. The model could well be used in planning for bed-capacity during outbreaks of other infectious diseases as well.",2005 May 11,"['Earnest, Arul', 'Chen, Mark I', 'Ng, Donald', 'Sin, Leo Yee']",BMC Health Serv Res,,,True
e2b435104da658ed6518247430cff1d428aae830,PMC,A simple and rapid approach for screening of SARS-coronavirus genotypes: an evaluation study,http://dx.doi.org/10.1186/1471-2334-5-87,PMC1276795,16229749,CC BY,"BACKGROUND: The Severe Acute Respiratory Syndrome (SARS) was a newly emerged infectious disease which caused a global epidemic in 2002–2003. Sequence analysis of SARS-coronavirus isolates revealed that specific genotypes predominated at different periods of the epidemic. This information can be used as a footprint for tracing the epidemiology of infections and monitor viral evolution. However, direct sequencing analysis of a large number of clinical samples is cumbersome and time consuming. We present here a simple and rapid assay for the screening of SARS-coronavirus genotypes based on the use of fluorogenic oligonucleotide probes for allelic discrimination. METHODS: Thirty SARS patients were recruited. Allelic discrimination assays were developed based on the use of fluorogenic oligonucleotide probes (TaqMan). Genotyping of the SARS-coronavirus isolates obtained from these patients were carried out by the allelic discrimination assays and confirmed by direct sequencing. RESULTS: Genotyping based on the allelic discrimination assays were fully concordant with direct sequencing. All of the 30 SARS-coronavirus genotypes studied were characteristic of genotypes previously documented to be associated with the latter part of the epidemic. Seven of the isolates contained a previously reported major deletion but in patients not epidemiologically related to the previously studied cohort. CONCLUSION: We have developed a simple and accurate method for the characterization and screening of SARS-coronavirus genotypes. It is a promising tool for the study of epidemiological relationships between documented cases during an outbreak.",2005 Oct 18,"['Chung, Grace TY', 'Chiu, Rossa WK', 'Cheung, Jo LK', 'Jin, Yongjie', 'Chim, Stephen SC', 'Chan, Paul KS', 'Lo, YM Dennis']",BMC Infect Dis,,,True
4c2205dd9943bdc4547fb999c6616269df83c685,PMC,Errata,,PMC1278499,,CC0,,2005 Apr,,Environ Health Perspect,,,True
c64fa46231a266d52eb5c7927dee12f7d55ae1b1,PMC,Correction: Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030428,PMC1283410,,CC BY,,2005 Nov 15,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,False
1c7b536966e355206379e97fd0e8ef71d71fb143,PMC,The Difficulties of Predicting the Outbreak Sizes of Epidemics,http://dx.doi.org/10.1371/journal.pmed.0030023,PMC1285070,,CC BY,,2006 Jan 22,,PLoS Med,,,True
ae19236936b05793ceac08ed5d58269c25486320,PMC,An ontology for immune epitopes: application to the design of a broad scope database of immune reactivities,http://dx.doi.org/10.1186/1745-7580-1-2,PMC1287064,16305755,CC BY,"BACKGROUND: Epitopes can be defined as the molecular structures bound by specific receptors, which are recognized during immune responses. The Immune Epitope Database and Analysis Resource (IEDB) project will catalog and organize information regarding antibody and T cell epitopes from infectious pathogens, experimental antigens and self-antigens, with a priority on NIAID Category A-C pathogens () and emerging/re-emerging infectious diseases. Both intrinsic structural and phylogenetic features, as well as information relating to the interactions of the epitopes with the host's immune system will be catalogued. DESCRIPTION: To effectively represent and communicate the information related to immune epitopes, a formal ontology was developed. The semantics of the epitope domain and related concepts were captured as a hierarchy of classes, which represent the general and specialized relationships between the various concepts. A complete listing of classes and their properties can be found at . CONCLUSION: The IEDB's ontology is the first ontology specifically designed to capture both intrinsic chemical and biochemical information relating to immune epitopes with information relating to the interaction of these structures with molecules derived from the host immune system. We anticipate that the development of this type of ontology and associated databases will facilitate rigorous description of data related to immune epitopes, and might ultimately lead to completely new methods for describing and modeling immune responses.",2005 Sep 20,"['Sathiamurthy, Muthuraman', 'Peters, Bjoern', 'Bui, Huynh-Hoa', 'Sidney, John', 'Mokili, John', 'Wilson, Stephen S', 'Fleri, Ward', 'McGuinness, Deborah L', 'Bourne, Philip E', 'Sette, Alessandro']",Immunome Res,,,True
db04140e4d00bc73a1f417761c2b84c3e5c53d73,PMC,An ontology for immune epitopes: application to the design of a broad scope database of immune reactivities,http://dx.doi.org/10.1186/1745-7580-1-2,PMC1287064,16305755,CC BY,"BACKGROUND: Epitopes can be defined as the molecular structures bound by specific receptors, which are recognized during immune responses. The Immune Epitope Database and Analysis Resource (IEDB) project will catalog and organize information regarding antibody and T cell epitopes from infectious pathogens, experimental antigens and self-antigens, with a priority on NIAID Category A-C pathogens () and emerging/re-emerging infectious diseases. Both intrinsic structural and phylogenetic features, as well as information relating to the interactions of the epitopes with the host's immune system will be catalogued. DESCRIPTION: To effectively represent and communicate the information related to immune epitopes, a formal ontology was developed. The semantics of the epitope domain and related concepts were captured as a hierarchy of classes, which represent the general and specialized relationships between the various concepts. A complete listing of classes and their properties can be found at . CONCLUSION: The IEDB's ontology is the first ontology specifically designed to capture both intrinsic chemical and biochemical information relating to immune epitopes with information relating to the interaction of these structures with molecules derived from the host immune system. We anticipate that the development of this type of ontology and associated databases will facilitate rigorous description of data related to immune epitopes, and might ultimately lead to completely new methods for describing and modeling immune responses.",2005 Sep 20,"['Sathiamurthy, Muthuraman', 'Peters, Bjoern', 'Bui, Huynh-Hoa', 'Sidney, John', 'Mokili, John', 'Wilson, Stephen S', 'Fleri, Ward', 'McGuinness, Deborah L', 'Bourne, Philip E', 'Sette, Alessandro']",Immunome Res,,,False
741878140cd73151d5bcb9d8a951b286434f148e,PMC,An ontology for immune epitopes: application to the design of a broad scope database of immune reactivities,http://dx.doi.org/10.1186/1745-7580-1-2,PMC1287064,16305755,CC BY,"BACKGROUND: Epitopes can be defined as the molecular structures bound by specific receptors, which are recognized during immune responses. The Immune Epitope Database and Analysis Resource (IEDB) project will catalog and organize information regarding antibody and T cell epitopes from infectious pathogens, experimental antigens and self-antigens, with a priority on NIAID Category A-C pathogens () and emerging/re-emerging infectious diseases. Both intrinsic structural and phylogenetic features, as well as information relating to the interactions of the epitopes with the host's immune system will be catalogued. DESCRIPTION: To effectively represent and communicate the information related to immune epitopes, a formal ontology was developed. The semantics of the epitope domain and related concepts were captured as a hierarchy of classes, which represent the general and specialized relationships between the various concepts. A complete listing of classes and their properties can be found at . CONCLUSION: The IEDB's ontology is the first ontology specifically designed to capture both intrinsic chemical and biochemical information relating to immune epitopes with information relating to the interaction of these structures with molecules derived from the host immune system. We anticipate that the development of this type of ontology and associated databases will facilitate rigorous description of data related to immune epitopes, and might ultimately lead to completely new methods for describing and modeling immune responses.",2005 Sep 20,"['Sathiamurthy, Muthuraman', 'Peters, Bjoern', 'Bui, Huynh-Hoa', 'Sidney, John', 'Mokili, John', 'Wilson, Stephen S', 'Fleri, Ward', 'McGuinness, Deborah L', 'Bourne, Philip E', 'Sette, Alessandro']",Immunome Res,,,False
c457f06e9474f83c6451e8740c24aebe35428408,PMC,Limits to Forecasting Precision for Outbreaks of Directly Transmitted Diseases,http://dx.doi.org/10.1371/journal.pmed.0030003,PMC1288026,16435887,CC BY,"BACKGROUND: Early warning systems for outbreaks of infectious diseases are an important application of the ecological theory of epidemics. A key variable predicted by early warning systems is the final outbreak size. However, for directly transmitted diseases, the stochastic contact process by which outbreaks develop entails fundamental limits to the precision with which the final size can be predicted. METHODS AND FINDINGS: I studied how the expected final outbreak size and the coefficient of variation in the final size of outbreaks scale with control effectiveness and the rate of infectious contacts in the simple stochastic epidemic. As examples, I parameterized this model with data on observed ranges for the basic reproductive ratio (R (0)) of nine directly transmitted diseases. I also present results from a new model, the simple stochastic epidemic with delayed-onset intervention, in which an initially supercritical outbreak (R (0) > 1) is brought under control after a delay. CONCLUSION: The coefficient of variation of final outbreak size in the subcritical case (R (0) < 1) will be greater than one for any outbreak in which the removal rate is less than approximately 2.41 times the rate of infectious contacts, implying that for many transmissible diseases precise forecasts of the final outbreak size will be unattainable. In the delayed-onset model, the coefficient of variation (CV) was generally large (CV > 1) and increased with the delay between the start of the epidemic and intervention, and with the average outbreak size. These results suggest that early warning systems for infectious diseases should not focus exclusively on predicting outbreak size but should consider other characteristics of outbreaks such as the timing of disease emergence.",2006 Jan 22,"Drake, John M",PLoS Med,,,True
74d006de3306bae5ae3710903fe05d743b6531f7,PMC,Limits to Forecasting Precision for Outbreaks of Directly Transmitted Diseases,http://dx.doi.org/10.1371/journal.pmed.0030003,PMC1288026,16435887,CC BY,"BACKGROUND: Early warning systems for outbreaks of infectious diseases are an important application of the ecological theory of epidemics. A key variable predicted by early warning systems is the final outbreak size. However, for directly transmitted diseases, the stochastic contact process by which outbreaks develop entails fundamental limits to the precision with which the final size can be predicted. METHODS AND FINDINGS: I studied how the expected final outbreak size and the coefficient of variation in the final size of outbreaks scale with control effectiveness and the rate of infectious contacts in the simple stochastic epidemic. As examples, I parameterized this model with data on observed ranges for the basic reproductive ratio (R (0)) of nine directly transmitted diseases. I also present results from a new model, the simple stochastic epidemic with delayed-onset intervention, in which an initially supercritical outbreak (R (0) > 1) is brought under control after a delay. CONCLUSION: The coefficient of variation of final outbreak size in the subcritical case (R (0) < 1) will be greater than one for any outbreak in which the removal rate is less than approximately 2.41 times the rate of infectious contacts, implying that for many transmissible diseases precise forecasts of the final outbreak size will be unattainable. In the delayed-onset model, the coefficient of variation (CV) was generally large (CV > 1) and increased with the delay between the start of the epidemic and intervention, and with the average outbreak size. These results suggest that early warning systems for infectious diseases should not focus exclusively on predicting outbreak size but should consider other characteristics of outbreaks such as the timing of disease emergence.",2006 Jan 22,"Drake, John M",PLoS Med,,,False
beb3c13102cceb2b4cb9345fed015c83a8b921ed,PMC,Limits to Forecasting Precision for Outbreaks of Directly Transmitted Diseases,http://dx.doi.org/10.1371/journal.pmed.0030003,PMC1288026,16435887,CC BY,"BACKGROUND: Early warning systems for outbreaks of infectious diseases are an important application of the ecological theory of epidemics. A key variable predicted by early warning systems is the final outbreak size. However, for directly transmitted diseases, the stochastic contact process by which outbreaks develop entails fundamental limits to the precision with which the final size can be predicted. METHODS AND FINDINGS: I studied how the expected final outbreak size and the coefficient of variation in the final size of outbreaks scale with control effectiveness and the rate of infectious contacts in the simple stochastic epidemic. As examples, I parameterized this model with data on observed ranges for the basic reproductive ratio (R (0)) of nine directly transmitted diseases. I also present results from a new model, the simple stochastic epidemic with delayed-onset intervention, in which an initially supercritical outbreak (R (0) > 1) is brought under control after a delay. CONCLUSION: The coefficient of variation of final outbreak size in the subcritical case (R (0) < 1) will be greater than one for any outbreak in which the removal rate is less than approximately 2.41 times the rate of infectious contacts, implying that for many transmissible diseases precise forecasts of the final outbreak size will be unattainable. In the delayed-onset model, the coefficient of variation (CV) was generally large (CV > 1) and increased with the delay between the start of the epidemic and intervention, and with the average outbreak size. These results suggest that early warning systems for infectious diseases should not focus exclusively on predicting outbreak size but should consider other characteristics of outbreaks such as the timing of disease emergence.",2006 Jan 22,"Drake, John M",PLoS Med,,,False
45654599b3a90fd3ecfb03ca55dee622a7565e94,PMC,Communication of bed allocation decisions in a critical care unit and accountability for reasonableness,http://dx.doi.org/10.1186/1472-6963-5-67,PMC1298296,16259634,CC BY,"BACKGROUND: Communication may affect perceptions of fair process for intensive care unit bed allocation decisions through its impact on the publicity condition of accountability for reasonableness. METHODS: We performed a qualitative case study to describe participant perceptions of the communication of bed allocation decisions in an 18-bed university affiliated, medical-surgical critical care unit at Sunnybrook and Women's College Health Sciences Centre. Interviewed participants were 3 critical care physicians, 4 clinical fellows in critical care, 4 resource nurses, 4 ""end-users"" (physicians who commonly referred patients to the unit), and 3 members of the administrative staff. Median bed occupancy during the study period (Jan-April 2003) was 18/18; daily admissions and discharges (median) were 3. We evaluated our description using the ethical framework ""accountability for reasonableness"" (A4R) to identify opportunities for improvement. RESULTS: The critical care physician, resource nurse, critical care fellow and end-users (trauma team leader, surgeons, neurosurgeons, anesthesiologists) functioned independently in unofficial ""parallel tracks"" of bed allocation decision-making; this conflicted with the official designation of the critical care physician as the sole authority. Communication between key decision-makers was indirect and could exclude those affected by the decisions; notably, family members. Participants perceived a lack of publicity for bed allocation rationales. CONCLUSION: The publicity condition should be improved for critical care bed allocation decisions. Decision-making in the ""parallel tracks"" we describe might be unavoidable within usual constraints of time, urgency and demand. Formal guidelines for direct communication between key participants in such circumstances would help to improve the fairness of these decisions.",2005 Oct 31,"['Cooper, Andrew B', 'Joglekar, Amit S', 'Gibson, Jennifer', 'Swota, Alissa H', 'Martin, Douglas K']",BMC Health Serv Res,,,True
07fc7bb8cbdb82bd4b17681aa92a6fc06d5fcf82,PMC,Functional and Genetic Analysis of Coronavirus Replicase-Transcriptase Proteins,http://dx.doi.org/10.1371/journal.ppat.0010039,PMC1298938,16341254,CC BY,"The coronavirus replicase-transcriptase complex is an assembly of viral and cellular proteins that mediate the synthesis of genome and subgenome-sized mRNAs in the virus-infected cell. Here, we report a genetic and functional analysis of 19 temperature-sensitive (ts) mutants of Murine hepatitis virus MHV-A59 that are unable to synthesize viral RNA when the infection is initiated and maintained at the non-permissive temperature. Both classical and biochemical complementation analysis leads us to predict that the majority of MHV-A59 ORF1a replicase gene products (non-structural proteins nsp1–nsp11) form a single complementation group (cistron1) while the replicase gene products encoded in ORF1b (non-structural proteins nsp12–nsp16) are able to function in trans and comprise at least three, and possibly five, further complementation groups (cistrons II–VI). Also, we have identified mutations in the non-structural proteins nsp 4, nsp5, nsp10, nsp12, nsp14, and nsp16 that are responsible for the ts phenotype of eight MHV-A59 mutants, which allows us to conclude that these proteins are essential for the assembly of a functional replicase-transcriptase complex. Finally, our analysis of viral RNA synthesis in ts mutant virus-infected cells allows us to discriminate three phenotypes with regard to the inability of specific mutants to synthesize viral RNA at the non-permissive temperature. Mutant LA ts6 appeared to be defective in continuing negative-strand synthesis, mutant Alb ts16 appeared to form negative strands but these were not utilized for positive-strand RNA synthesis, and mutant Alb ts22 was defective in the elongation of both positive- and negative-strand RNA. On the basis of these results, we propose a model that describes a pathway for viral RNA synthesis in MHV-A59-infected cells. Further biochemical analysis of these mutants should allow us to identify intermediates in this pathway and elucidate the precise function(s) of the viral replicase proteins involved.",2005 Dec 9,"['Sawicki, Stanley G', 'Sawicki, Dorothea L', 'Younker, Diane', 'Meyer, Yvonne', 'Thiel, Volker', 'Stokes, Helen', 'Siddell, Stuart G']",PLoS Pathog,,,True
56bea8bc53d2703d7d33244508932aa26d1ad442,PMC,RNA Viral Community in Human Feces: Prevalence of Plant Pathogenic Viruses,http://dx.doi.org/10.1371/journal.pbio.0040003,PMC1310650,16336043,CC BY,"The human gut is known to be a reservoir of a wide variety of microbes, including viruses. Many RNA viruses are known to be associated with gastroenteritis; however, the enteric RNA viral community present in healthy humans has not been described. Here, we present a comparative metagenomic analysis of the RNA viruses found in three fecal samples from two healthy human individuals. For this study, uncultured viruses were concentrated by tangential flow filtration, and viral RNA was extracted and cloned into shotgun viral cDNA libraries for sequencing analysis. The vast majority of the 36,769 viral sequences obtained were similar to plant pathogenic RNA viruses. The most abundant fecal virus in this study was pepper mild mottle virus (PMMV), which was found in high concentrations—up to 10(9) virions per gram of dry weight fecal matter. PMMV was also detected in 12 (66.7%) of 18 fecal samples collected from healthy individuals on two continents, indicating that this plant virus is prevalent in the human population. A number of pepper-based foods tested positive for PMMV, suggesting dietary origins for this virus. Intriguingly, the fecal PMMV was infectious to host plants, suggesting that humans might act as a vehicle for the dissemination of certain plant viruses.",2006 Jan 20,"['Zhang, Tao', 'Breitbart, Mya', 'Lee, Wah Heng', 'Run, Jin-Quan', 'Wei, Chia Lin', 'Soh, Shirlena Wee Ling', 'Hibberd, Martin L', 'Liu, Edison T', 'Rohwer, Forest', 'Ruan, Yijun']",PLoS Biol,,,True
0a1533470817bc5ef0d0d0af56386a96b505dc0d,PMC,Evaluation of potential reference genes in real-time RT-PCR studies of Atlantic salmon,http://dx.doi.org/10.1186/1471-2199-6-21,PMC1314898,16293192,CC BY,"BACKGROUND: Salmonid fishes are among the most widely studied model fish species but reports on systematic evaluation of reference genes in qRT-PCR studies is lacking. RESULTS: The stability of six potential reference genes was examined in eight tissues of Atlantic salmon (Salmo salar), to determine the most suitable genes to be used in quantitative real-time RT-PCR analyses. The relative transcription levels of genes encoding 18S rRNA, S20 ribosomal protein, β-actin, glyceraldehyde-3P-dehydrogenase (GAPDH), and two paralog genes encoding elongation factor 1A (EF1A(A )and EF1A(B)) were quantified in gills, liver, head kidney, spleen, thymus, brain, muscle, and posterior intestine in six untreated adult fish, in addition to a group of individuals that went through smoltification. Based on calculations performed with the geNorm VBA applet, which determines the most stable genes from a set of tested genes in a given cDNA sample, the ranking of the examined genes in adult Atlantic salmon was EF1A(B)>EF1A(A)>β-actin>18S rRNA>S20>GAPDH. When the same calculations were done on a total of 24 individuals from four stages in the smoltification process (presmolt, smolt, smoltified seawater and desmoltified freshwater), the gene ranking was EF1A(B)>EF1A(A)>S20>β-actin>18S rRNA>GAPDH. CONCLUSION: Overall, this work suggests that the EF1A(A )and EF1A(B )genes can be useful as reference genes in qRT-PCR examination of gene expression in the Atlantic salmon.",2005 Nov 17,"['Olsvik, Pål A', 'Lie, Kai K', 'Jordal, Ann-Elise O', 'Nilsen, Tom O', 'Hordvik, Ivar']",BMC Mol Biol,,,True
86adefc2b5acac8a4ca321db6db5ec03408f07bd,PMC,Ecological Change: Life Lessons,,PMC1314962,,CC0,,2005 Dec,"Bonn, Dorothy",Environ Health Perspect,,,True
2739ea989ec040104223cfb49d2a13d7d89dc79a,PMC,Selection of reference genes for quantitative real-time PCR in bovine preimplantation embryos,http://dx.doi.org/10.1186/1471-213X-5-27,PMC1315359,16324220,CC BY,"BACKGROUND: Real-time quantitative PCR is a sensitive and very efficient technique to examine gene transcription patterns in preimplantation embryos, in order to gain information about embryo development and to optimize assisted reproductive technologies. Critical to the succesful application of real-time PCR is careful assay design, reaction optimization and validation to maximize sensitivity and accuracy. In most of the studies published GAPD, ACTB or 18S rRNA have been used as a single reference gene without prior verification of their expression stability. Normalization of the data using unstable controls can result in erroneous conclusions, especially when only one reference gene is used. RESULTS: In this study the transcription levels of 8 commonly used reference genes (ACTB, GAPD, Histone H2A, TBP, HPRT1, SDHA, YWHAZ and 18S rRNA) were determined at different preimplantation stages (2-cell, 8-cell, blastocyst and hatched blastocyst) in order to select the most stable genes to normalize quantitative data within different preimplantation embryo stages. CONCLUSION: Using the geNorm application YWHAZ, GAPD and SDHA were found to be the most stable genes across the examined embryonic stages, while the commonly used ACTB was shown to be highly regulated. We recommend the use of the geometric mean of those 3 reference genes as an accurate normalization factor, which allows small expression differences to be reliably measured.",2005 Dec 3,"['Goossens, Karen', 'Van Poucke, Mario', 'Van Soom, Ann', 'Vandesompele, Jo', 'Van Zeveren, Alex', 'Peelman, Luc J']",BMC Dev Biol,,,True
c82d59add457527b2858fb5157a92634815d9387,PMC,The New International Health Regulations and the Federalism Dilemma,http://dx.doi.org/10.1371/journal.pmed.0030001,PMC1315361,16354103,CC BY,"The recent revision of the International Health Regulations, say Wilson and colleagues, is both long overdue and eminently necessary to face the challenges of an increasingly globalized world.",2006 Jan 20,"['Wilson, Kumanan', 'McDougall, Christopher', 'Upshur, Ross']",PLoS Med,,,True
e97ccc39b73b40f090df148361e6326f0a5798b6,PMC,Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells,http://dx.doi.org/10.1186/1465-9921-6-135,PMC1318487,16283933,CC BY,"BACKGROUND: Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10). Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10) from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells. METHODS: We used quantitative RT-PCR and ELISA to compare the profile of cytokine and chemokine gene expression induced by H5N1 viruses A/HK/483/97 (H5N1/97), A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04) with that of human H1N1 virus in human primary alveolar and bronchial epithelial cells in vitro. RESULTS: We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04) appeared to be even more potent at inducing IP-10 than H5N1/97 virus. CONCLUSION: The H5N1/97 and H5N1/04 subtype influenza A viruses are more potent inducers of proinflammatory cytokines and chemokines in primary human respiratory epithelial cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines may be relevant to the pathogenesis of human H5N1 disease.",2005 Nov 11,"['Chan, MCW', 'Cheung, CY', 'Chui, WH', 'Tsao, SW', 'Nicholls, JM', 'Chan, YO', 'Chan, RWY', 'Long, HT', 'Poon, LLM', 'Guan, Y', 'Peiris, JSM']",Respir Res,,,True
a5add18a3b3f98e15c3afcc6186642140033d975,PMC,Promoter Variation in the DC-SIGN–Encoding Gene CD209 Is Associated with Tuberculosis,http://dx.doi.org/10.1371/journal.pmed.0030020,PMC1324949,16379498,CC BY,"BACKGROUND: Tuberculosis, which is caused by Mycobacterium tuberculosis, remains one of the leading causes of mortality worldwide. The C-type lectin DC-SIGN is known to be the major M. tuberculosis receptor on human dendritic cells. We reasoned that if DC-SIGN interacts with M. tuberculosis, as well as with other pathogens, variation in this gene might have a broad range of influence in the pathogenesis of a number of infectious diseases, including tuberculosis. METHODS AND FINDINGS: We tested whether polymorphisms in CD209, the gene encoding DC-SIGN, are associated with susceptibility to tuberculosis through sequencing and genotyping analyses in a South African cohort. After exclusion of significant population stratification in our cohort, we observed an association between two CD209 promoter variants (−871G and −336A) and decreased risk of developing tuberculosis. By looking at the geographical distribution of these variants, we observed that their allelic combination is mainly confined to Eurasian populations. CONCLUSIONS: Our observations suggest that the two −871G and −336A variants confer protection against tuberculosis. In addition, the geographic distribution of these two alleles, together with their phylogenetic status, suggest that they may have increased in frequency in non-African populations as a result of host genetic adaptation to a longer history of exposure to tuberculosis. Further characterization of the biological consequences of DC-SIGN variation in tuberculosis will be crucial to better appreciate the role of this lectin in interactions between the host immune system and the tubercle bacillus as well as other pathogens.",2006 Feb 3,"['Barreiro, Luis B', 'Neyrolles, Olivier', 'Babb, Chantal L', 'Tailleux, Ludovic', 'Quach, Hélène', 'McElreavey, Ken', 'van Helden, Paul D.', 'Hoal, Eileen G', 'Gicquel, Brigitte', 'Quintana-Murci, Lluis']",PLoS Med,,,True
325688eb32f8e6875a930f831c4cea02b2a556c9,PMC,Time Course and Cellular Localization of SARS-CoV Nucleoprotein and RNA in Lungs from Fatal Cases of SARS,http://dx.doi.org/10.1371/journal.pmed.0030027,PMC1324951,16379499,CC BY,"BACKGROUND: Cellular localization of severe acute respiratory syndrome coronavirus (SARS-CoV) in the lungs of patients with SARS is important in confirming the etiological association of the virus with disease as well as in understanding the pathogenesis of the disease. To our knowledge, there have been no comprehensive studies investigating viral infection at the cellular level in humans. METHODS AND FINDINGS: We collected the largest series of fatal cases of SARS with autopsy material to date by merging the pathological material from two regions involved in the 2003 worldwide SARS outbreak in Hong Kong, China, and Toronto, Canada. We developed a monoclonal antibody against the SARS-CoV nucleoprotein and used it together with in situ hybridization (ISH) to analyze the autopsy lung tissues of 32 patients with SARS from Hong Kong and Toronto. We compared the results of these assays with the pulmonary pathologies and the clinical course of illness for each patient. SARS-CoV nucleoprotein and RNA were detected by immunohistochemistry and ISH, respectively, primarily in alveolar pneumocytes and, less frequently, in macrophages. Such localization was detected in four of the seven patients who died within two weeks of illness onset, and in none of the 25 patients who died later than two weeks after symptom onset. CONCLUSIONS: The pulmonary alveolar epithelium is the chief target of SARS-CoV, with macrophages infected subsequently. Viral replication appears to be limited to the first two weeks after symptom onset, with little evidence of continued widespread replication after this period. If antiviral therapy is considered for future treatment, it should be focused on this two-week period of acute clinical disease.",2006 Feb 3,"['Nicholls, John M', 'Butany, Jagdish', 'Poon, Leo L. M', 'Chan, Kwok H', 'Beh, Swan Lip', 'Poutanen, Susan', 'Peiris, J. S. Malik', 'Wong, Maria']",PLoS Med,,,True
038f6e6dbf6b5d3b0ab71e5f20dadb4cf675cd0b,PMC,Pathological Clues to How the SARS Virus Kills,http://dx.doi.org/10.1371/journal.pmed.0030059,PMC1324952,,CC BY,,2006 Feb 3,,PLoS Med,,,False
58bb44f68691a167fdfb89c3a90f8fe520e37d06,PMC,Lung Infection—A Public Health Priority,http://dx.doi.org/10.1371/journal.pmed.0030076,PMC1326257,16401173,CC BY,"The pervasive burden of lung infections receives proportionately little attention from the biomedical and public health communities, argues Mizgerd.",2006 Feb 17,"Mizgerd, Joseph P",PLoS Med,,,True
c6202f96bd4b2aea699d5fbe867f311498dca3aa,PMC,Bioethical Implications of Globalization: An International Consortium Project of the European Commission,http://dx.doi.org/10.1371/journal.pmed.0030043,PMC1351155,16420098,CC BY,The BIG project looks at some of the ethical concerns surrounding globalization and health.,2006 Feb 24,"['Novotny, Thomas E', 'Mordini, Emilio', 'Chadwick, Ruth', 'Pedersen, J. Martin', 'Fabbri, Fabrizio', 'Lie, Reidar', 'Thanachaiboot, Natapong', 'Mossialos, Elias', 'Permanand, Govin']",PLoS Med,,,True
a78fd1b34372e1e54bf2a192d04aa36670cea307,PMC,Public awareness of risk factors for cancer among the Japanese general population: A population-based survey,http://dx.doi.org/10.1186/1471-2458-6-2,PMC1351169,16403223,CC BY,"BACKGROUND: The present study aimed to provide information on awareness of the attributable fraction of cancer causes among the Japanese general population. METHODS: A nationwide representative sample of 2,000 Japanese aged 20 or older was asked about their perception and level of concern about various environmental and genetic risk factors in relation to cancer prevention, as a part of an Omnibus Survey. Interviews were conducted with 1,355 subjects (609 men and 746 women). RESULTS: Among 12 risk factor candidates, the attributable fraction of cancer-causing viral and bacterial infection was considered highest (51%), followed by that of tobacco smoking (43%), stress (39%), and endocrine-disrupting chemicals (37%). On the other hand, the attributable fractions of cancer by charred fish and meat (21%) and alcohol drinking (22%) were considered low compared with other risk factor candidates. For most risk factors, attributable fraction responses were higher in women than in men. As a whole, the subjects tended to respond with higher values than those estimated by epidemiologic evidence in the West. The attributable fraction of cancer speculated to be genetically determined was 32%, while 36% of cancer was considered preventable by improving lifestyle. CONCLUSION: Our results suggest that awareness of the attributable fraction of cancer causes in the Japanese general population tends to be dominated by cancer-causing infection, occupational exposure, air pollution and food additives rather than major lifestyle factors such as diet.",2006 Jan 10,"['Inoue, Manami', 'Iwasaki, Motoki', 'Otani, Tetsuya', 'Sasazuki, Shizuka', 'Tsugane, Shoichiro']",BMC Public Health,,,True
75025fdc2dbeab398880d6e072274409f3dc14bd,PMC,ZCURVE_V: a new self-training system for recognizing protein-coding genes in viral and phage genomes,http://dx.doi.org/10.1186/1471-2105-7-9,PMC1352377,16401352,CC BY,"BACKGROUND: It necessary to use highly accurate and statistics-based systems for viral and phage genome annotations. The GeneMark systems for gene-finding in virus and phage genomes suffer from some basic drawbacks. This paper puts forward an alternative approach for viral and phage gene-finding to improve the quality of annotations, particularly for newly sequenced genomes. RESULTS: The new system ZCURVE_V has been run for 979 viral and 212 phage genomes, respectively, and satisfactory results are obtained. To have a fair comparison with the currently available software of similar function, GeneMark, a total of 30 viral genomes that have not been annotated by GeneMark are selected to be tested. Consequently, the average specificity of both systems is well matched, however the average sensitivity of ZCURVE_V for smaller viral genomes (< 100 kb), which constitute the main parts of viral genomes sequenced so far, is higher than that of GeneMark. Additionally, for the genome of Amsacta moorei entomopoxvirus, probably with the lowest genomic GC content among the sequenced organisms, the accuracy of ZCURVE_V is much better than that of GeneMark, because the later predicts hundreds of false-positive genes. ZCURVE_V is also used to analyze well-studied genomes, such as HIV-1, HBV and SARS-CoV. Accordingly, the performance of ZCURVE_V is generally better than that of GeneMark. Finally, ZCURVE_V may be downloaded and run locally, particularly facilitating its utilization, whereas GeneMark is not downloadable. Based on the above comparison, it is suggested that ZCURVE_V may serve as a preferred gene-finding tool for viral and phage genomes newly sequenced. However, it is also shown that the joint application of both systems, ZCURVE_V and GeneMark, leads to better gene-finding results. The system ZCURVE_V is freely available at: . CONCLUSION: ZCURVE_V may serve as a preferred gene-finding tool used for viral and phage genomes, especially for anonymous viral and phage genomes newly sequenced.",2006 Jan 10,"['Guo, Feng-Biao', 'Zhang, Chun-Ting']",BMC Bioinformatics,,,True
2f9f32fc7d8af64617d6bbd88c7a42dec0e13a90,PMC,Evidence of host-virus co-evolution in tetranucleotide usage patterns of bacteriophages and eukaryotic viruses,http://dx.doi.org/10.1186/1471-2164-7-8,PMC1360066,16417644,CC BY,"BACKGROUND: Virus taxonomy is based on morphologic characteristics, as there are no widely used non-phenotypic measures for comparison among virus families. We examined whether there is phylogenetic signal in virus nucleotide usage patterns that can be used to determine ancestral relationships. The well-studied model of tail morphology in bacteriophage classification was used for comparison with nucleotide usage patterns. Tetranucleotide usage deviation (TUD) patterns were chosen since they have previously been shown to contain phylogenetic signal similar to that of 16S rRNA. RESULTS: We found that bacteriophages have unique TUD patterns, representing genomic signatures that are relatively conserved among those with similar host range. Analysis of TUD-based phylogeny indicates that host influences are important in bacteriophage evolution, and phylogenies containing both phages and their hosts support their co-evolution. TUD-based phylogeny of eukaryotic viruses indicates that they cluster largely based on nucleic acid type and genome size. Similarities between eukaryotic virus phylogenies based on TUD and gene content substantiate the TUD methodology. CONCLUSION: Differences between phenotypic and TUD analysis may provide clues to virus ancestry not previously inferred. As such, TUD analysis provides a complementary approach to morphology-based systems in analysis of virus evolution.",2006 Jan 18,"['Pride, David T', 'Wassenaar, Trudy M', 'Ghose, Chandrabali', 'Blaser, Martin J']",BMC Genomics,,,True
c6bf372c094f035a514975c35a7f9c094abbe493,PMC,Sequence specific visual detection of LAMP reactions by addition of cationic polymers,http://dx.doi.org/10.1186/1472-6750-6-3,PMC1373654,16401354,CC BY,"BACKGROUND: Development of a practical gene point-of-care testing device (g-POCT device) requires innovative detection methods for demonstrating the results of the gene amplification reaction without the use of expensive equipment. We have studied a new method for the sequence-specific visual detection of minute amounts of nucleic acids using precipitation reaction by addition of cationic polymers to amplicons of Loop mediated isothermal Amplification (LAMP). RESULTS: Oligo DNA probes labeled with different fluorescent dyes were prepared for multiple nucleic acid templates, and the templates were amplified by the LAMP reactions under the existence of the probes. At completion of the LAMP reaction, an optimal amount of low molecular weight polyethylenimine (PEI) was added, resulting in the precipitation of the insoluble LAMP amplicon-PEI complex. The fluorescently labeled Oligo DNA probes hybridized to the LAMP product were incorporated into the precipitation, and the precipitate emitted fluorescence corresponding to the amplified nucleic acid templates. The color of emitted fluorescence can be detected easily by naked eye on a conventional UV illuminator. CONCLUSION: The presence or absence of minute amount of nucleic acid templates could be detected in a simple manner through visual assessment for the color of the LAMP amplicon-PEI complex precipitate. We conclude that this detection method may facilitate development of small and simple g-POCT device.",2006 Jan 10,"['Mori, Yasuyoshi', 'Hirano, Tsuyoshi', 'Notomi, Tsugunori']",BMC Biotechnol,,,True
882b4b4a41b772d31e8f9e860882088336f26e26,PMC,Automated extraction protocol for quantification of SARS-Coronavirus RNA in serum: an evaluation study,http://dx.doi.org/10.1186/1471-2334-6-20,PMC1382231,16466582,CC BY,"BACKGROUND: We have previously developed a test for the diagnosis and prognostic assessment of the severe acute respiratory syndrome (SARS) based on the detection of the SARS-coronavirus RNA in serum by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). In this study, we evaluated the feasibility of automating the serum RNA extraction procedure in order to increase the throughput of the assay. METHODS: An automated nucleic acid extraction platform using the MagNA Pure LC instrument (Roche Diagnostics) was evaluated. We developed a modified protocol in compliance with the recommended biosafety guidelines from the World Health Organization based on the use of the MagNA Pure total nucleic acid large volume isolation kit for the extraction of SARS-coronavirus RNA. The modified protocol was compared with a column-based extraction kit (QIAamp viral RNA mini kit, Qiagen) for quantitative performance, analytical sensitivity and precision. RESULTS: The newly developed automated protocol was shown to be free from carry-over contamination and have comparable performance with other standard protocols and kits designed for the MagNA Pure LC instrument. However, the automated method was found to be less sensitive, less precise and led to consistently lower serum SARS-coronavirus concentrations when compared with the column-based extraction method. CONCLUSION: As the diagnostic efficiency and prognostic value of the serum SARS-CoV RNA RT-PCR test is critically associated with the analytical sensitivity and quantitative performance contributed both by the RNA extraction and RT-PCR components of the test, we recommend the use of the column-based manual RNA extraction method.",2006 Feb 9,"['Chiu, Rossa WK', 'Jin, Yongjie', 'Chung, Grace TY', 'Lui, Wing-bong', 'Chan, Anthony TC', 'Lim, Wilina', 'Dennis Lo, YM']",BMC Infect Dis,,,True
abb703e29b1ee7ddf60006b33de199828666d7b1,PMC,The Scientific Response to a Pandemic,http://dx.doi.org/10.1371/journal.ppat.0020009,PMC1383484,16738708,CC BY,,2006 Feb 24,"['Gronvall, Gigi Kwik', 'Waldhorn, Richard E', 'Henderson, D. A']",PLoS Pathog,,,True
c9eb97be96131dee33d53b03c46dacecf63c02b1,PMC,Correction: Functional and Genetic Analysis of Coronavirus Replicase-Transcriptase Proteins,http://dx.doi.org/10.1371/journal.ppat.0020017,PMC1383490,,CC BY,,2006 Feb 24,"['Sawicki, Stanley G', 'Sawicki, Dorothea L', 'Younker, Diane', 'Meyer, Yvonne', 'Thiel, Volker', 'Stokes, Helen', 'Siddell, Stuart G']",PLoS Pathog,,,True
66a1d5898c1fb5c8e8554f92e446d262abb10fdb,PMC,Correlation between the presence of neutralizing antibodies against porcine circovirus 2 (PCV2) and protection against replication of the virus and development of PCV2-associated disease,http://dx.doi.org/10.1186/1746-6148-2-6,PMC1386657,16445856,CC BY,"BACKGROUND: In a previous study, it was demonstrated that high replication of Porcine circovirus 2 (PCV2) in a gnotobiotic pig was correlated with the absence of PCV2-neutralizing antibodies. The aim of the present study was to investigate if this correlation could also be found in SPF pigs in which PMWS was experimentally reproduced and in naturally PMWS-affected pigs. RESULTS: When looking at the total anti-PCV2 antibody titres, PMWS-affected and healthy animals seroconverted at the same time point, and titres in PMWS-affected animals were only slightly lower compared to those in healthy animals. In healthy animals, the evolution of PCV2-neutralizing antibodies coincided with that of total antibodies. In PMWS-affected animals, neutralizing antibodies could either not be found (sera from field studies) or were detected in low titres between 7 and 14 DPI only (sera from experimentally inoculated SPF pigs). Differences were also found in the evolution of specific antibody isotypes titres against PCV2. In healthy pigs, IgM antibodies persisted until the end of the study, whereas in PMWS-affected pigs they quickly decreased or remained present at low titres. The mean titres of other antibody isotypes (IgG1, IgG2 and IgA), were slightly lower in PMWS-affected pigs compared to their healthy group mates at the end of each study. CONCLUSION: This study describes important differences in the development of the humoral immune response between pigs that get subclinically infected with PCV2 and pigs that experience a high level of PCV2-replication which in 3 of 4 experiments led to the development of PMWS. These observations may contribute to a better understanding of the pathogenesis of a PCV2-infection.",2006 Jan 30,"['Meerts, Peter', 'Misinzo, Gerald', 'Lefebvre, David', 'Nielsen, Jens', 'Bøtner, Anette', 'Kristensen, Charlotte S', 'Nauwynck, Hans J']",BMC Vet Res,,,True
f50562c5a5e9f206dba3c559e6b4f5b65aadf7f4,PMC,Epstein-barr virus induced cellular changes in nasal mucosa,http://dx.doi.org/10.1186/1743-422X-3-6,PMC1388193,16451721,CC BY,"A 21-year-old man presented with nasal obstruction of the right nasal fossa of 1 year duration. Nasal endoscopy revealed in the right inferior turbinate head a rounded neoplasm about 1 cm in diameter. Cytologic study of a nasal scraping specimen disclosed numerous clusters containing columnar cells with cytomegaly, prominent multinucleation, markedly sparse shortened cilia; the cytoplasm contained an acidophil area and a small round area that stained poorly; cells with a large intracytoplasmic vacuole that was acidophil and PAS+. Serology tests using the nested polymer chain reaction (PCR) technique on serum, nasal and pharyngeal smears revealed an Epstein-Barr virus (EBV) infection that was confirmed at electron microscopy. The clinical and cytological features resolved 19 months after the initial evaluation. CONCLUSION: The authors advise carrying out clinical (endoscopy, serology, etc.) evaluation of all endonasal neoplasms and to routinely perform cytological study on nasal scraping specimens. When samples test positive for EBV, nasal and nasopharyngeal endoscopy should be performed regularly to detect possible evidence for nasopharyngeal carcinoma (NPC).",2006 Feb 1,"['Gelardi, Matteo', 'Tomaiuolo, Marilena', 'Cassano, Michele', 'Besozzi, Gaspare', 'Fiorella, Maria Luisa', 'Calvario, Agata', 'Castellano, Maria Antonia', 'Cassano, Pasquale']",Virol J,,,True
f50b6632623eb4fe2193588b4f2c217c7125872d,PMC,Virus-mediated autoimmunity in Multiple Sclerosis,http://dx.doi.org/10.1186/1740-2557-3-1,PMC1397830,16504001,CC BY,"Epidemiological data suggest the notion that in Multiple Sclerosis (MS) is an acquired autoimmune disease and the cause may be an environmental factor(s), probably infectious, in genetically susceptible individuals. Several cases of viral induced demyelinatimg encephalomyelitis in human beings and in experimental models as well as the presence of IgG oligoclonal bands in the cerebrospinal fluid indicate that the infectious factor may be viral. However, the absence of a specific virus identification in MS central nervous system may hardly support this notion. On the other hand, the partial response of patients with MS to immunosuppressive and immunomodulatory therapy support the evidence of an autoimmune etiology for MS. However, the autoimmune hypothesis shares the same criticism with the infectious one in that no autoantigen(s) specific to and causative for MS has ever been identified. Nevertheless, the absence of identifiable infectious agent, especially viral does not rule out its presence at a certain time – point and the concomitant long term triggering of an autoimmune cascade of events thereafter. Several concepts have emerged in an attempt to explain the autoimmune mechanisms and ongoing neurodegeneration in MS on the basis of the infectious – viral hypothesis.",2006 Feb 19,"['Grigoriadis, Nikolaos', 'Hadjigeorgiou, Georgios M']",J Autoimmune Dis,,,True
5f50a65482a507e61c9a7cd9a9b80a0017494dcb,PMC,"Globalization, migration health, and educational preparation for transnational medical encounters",http://dx.doi.org/10.1186/1744-8603-2-2,PMC1403753,16441899,CC BY,"Unprecedented migration, a core dimension of contemporary globalization, challenges population health. In a world of increasing human mobility, many health outcomes are shaped by transnational interactions among care providers and care recipients who meet in settings where nationality/ethnic match is not an option. This review article explores the value of transnational competence (TC) education as preparation for ethnically and socially discordant clinical encounters. The relevance of TC's five core skill domains (analytic, emotional, creative, communicative, and functional) for migration health and the medical-school curriculum is elaborated. A pedagogical approach that prepares for the transnational health-care consultation is presented, with a focus on clinical-clerkship learning experiences. Educational preparation for contemporary medical encounters needs to include a comprehensive set of patient-focused interpersonal skills, be adaptable to a wide variety of service users and global practice sites, and possess utility in addressing both the quality of patient care and socio-political constraints on migration health.",2006 Jan 30,"Koehn, Peter H",Global Health,,,True
dff11250a455815390e0d3c8a6208f608aa681ec,PMC,Developing nucleic acid-based electrical detection systems,http://dx.doi.org/10.1186/1475-2859-5-9,PMC1420323,16512917,CC BY,"Development of nucleic acid-based detection systems is the main focus of many research groups and high technology companies. The enormous work done in this field is particularly due to the broad versatility and variety of these sensing devices. From optical to electrical systems, from label-dependent to label-free approaches, from single to multi-analyte and array formats, this wide range of possibilities makes the research field very diversified and competitive. New challenges and requirements for an ideal detector suitable for nucleic acid analysis include high sensitivity and high specificity protocol that can be completed in a relatively short time offering at the same time low detection limit. Moreover, systems that can be miniaturized and automated present a significant advantage over conventional technology, especially if detection is needed in the field. Electrical system technology for nucleic acid-based detection is an enabling mode for making miniaturized to micro- and nanometer scale bio-monitoring devices via the fusion of modern micro- and nanofabrication technology and molecular biotechnology. The electrical biosensors that rely on the conversion of the Watson-Crick base-pair recognition event into a useful electrical signal are advancing rapidly, and recently are receiving much attention as a valuable tool for microbial pathogen detection. Pathogens may pose a serious threat to humans, animal and plants, thus their detection and analysis is a significant element of public health. Although different conventional methods for detection of pathogenic microorganisms and their toxins exist and are currently being applied, improvements of molecular-based detection methodologies have changed these traditional detection techniques and introduced a new era of rapid, miniaturized and automated electrical chip detection technologies into pathogen identification sector. In this review some developments and current directions in nucleic acid-based electrical detection are discussed.",2006 Mar 2,"Gabig-Ciminska, Magdalena",Microb Cell Fact,,,True
dca1ffcfcd6a2b7c8495e77c438d6b91d065bbf5,PMC,Specific detection of H5N1 avian influenza A virus in field specimens by a one-step RT-PCR assay,http://dx.doi.org/10.1186/1471-2334-6-40,PMC1421410,16512903,CC BY,"BACKGROUND: Continuous outbreaks of the highly pathogenic H5N1 avian influenza A in Asia has resulted in an urgent effort to improve current diagnostics to aid containment of the virus and lower the threat of a influenza pandemic. We report here the development of a PCR-based assay that is highly specific for the H5N1 avian influenza A virus. METHODS: A one-step reverse-transcription PCR assay was developed to detect the H5N1 avian influenza A virus. The specificity of the assay was shown by testing sub-types of influenza A virus and other viral and bacterial pathogens; and on field samples. RESULTS: Validation on 145 field specimens from Vietnam and Malaysia showed that the assay was specific without cross reactivity to a number of other infuenza strains as well as human respiratory related pathogens. Detection was 100% from allantoic fluid in H5N1 positive samples, suggesting it to be a reliable sampling source for accurate detection. CONCLUSION: The assay developed from this study indicates that the primers are specific for the H5N1 influenza virus. As shown by the field tested results, this assay would be highly useful as a diagnostic tool to help identify and control influenza epidemics.",2006 Mar 2,"['Ng, Lisa FP', 'Barr, Ian', 'Nguyen, Tung', 'Noor, Suriani Mohd', 'Tan, Rosemary Sok-Pin', 'Agathe, Lora V', 'Gupta, Sanjay', 'Khalil, Hassuzana', 'To, Thanh Long', 'Hassan, Sharifah Syed', 'Ren, Ee-Chee']",BMC Infect Dis,,,True
5b8bd7273e2cd3875283e705102b12ddf38d25c8,PMC,"Using Ontario's ""Telehealth"" health telephone helpline as an early-warning system: a study protocol",http://dx.doi.org/10.1186/1472-6963-6-10,PMC1431529,16480500,CC BY,"BACKGROUND: The science of syndromic surveillance is still very much in its infancy. While a number of syndromic surveillance systems are being evaluated in the US, very few have had success thus far in predicting an infectious disease event. Furthermore, to date, the majority of syndromic surveillance systems have been based primarily in emergency department settings, with varying levels of enhancement from other data sources. While research has been done on the value of telephone helplines on health care use and patient satisfaction, very few projects have looked at using a telephone helpline as a source of data for syndromic surveillance, and none have been attempted in Canada. The notable exception to this statement has been in the UK where research using the national NHS Direct system as a syndromic surveillance tool has been conducted. METHODS/DESIGN: The purpose of our proposed study is to evaluate the effectiveness of Ontario's telephone nursing helpline system as a real-time syndromic surveillance system, and how its implementation, if successful, would have an impact on outbreak event detection in Ontario. Using data collected retrospectively, all ""reasons for call"" and assigned algorithms will be linked to a syndrome category. Using different analytic methods, normal thresholds for the different syndromes will be ascertained. This will allow for the evaluation of the system's sensitivity, specificity and positive predictive value. The next step will include the prospective monitoring of syndromic activity, both temporally and spatially. DISCUSSION: As this is a study protocol, there are currently no results to report. However, this study has been granted ethical approval, and is now being implemented. It is our hope that this syndromic surveillance system will display high sensitivity and specificity in detecting true outbreaks within Ontario, before they are detected by conventional surveillance systems. Future results will be published in peer-reviewed journals so as to contribute to the growing body of evidence on syndromic surveillance, while also providing an non US-centric perspective.",2006 Feb 15,"['Rolland, Elizabeth', 'Moore, Kieran M', 'Robinson, Victoria A', 'McGuinness, Don']",BMC Health Serv Res,,,True
5208ab18e0b8b851eabda0c5c83c1d31156da8e0,PMC,Evolution of the uniquely adaptable lentiviral envelope in a natural reservoir host,http://dx.doi.org/10.1186/1742-4690-3-19,PMC1431560,16549011,CC BY,"BACKGROUND: The ability of emerging pathogens to infect new species is likely related to the diversity of pathogen variants present in existing reservoirs and their degree of genomic plasticity, which determines their ability to adapt to new environments. Certain simian immunodeficiency viruses (SIVcpz, SIVsm) have demonstrated tremendous success in infecting new species, including humans, resulting in the HIV-1 and HIV-2 epidemics. Although SIV diversification has been studied on a population level, the essential substrates for cross-species transmission, namely SIV sequence diversity and the types and extent of viral diversification present in individual reservoir animals have not been elucidated. To characterize this intra-host SIV diversity, we performed sequence analyses of clonal viral envelope (env) V1V2 and gag p27 variants present in individual SIVsm-infected sooty mangabeys over time. RESULTS: SIVsm demonstrated extensive intra-animal V1V2 length variation and amino acid diversity (le38%), and continual variation in V1V2 N-linked glycosylation consensus sequence frequency and location. Positive selection was the predominant evolutionary force. Temporal sequence shifts suggested continual selection, likely due to evolving antibody responses. In contrast, gag p27 was predominantly under purifying selection. SIVsm V1V2 sequence diversification is at least as great as that in HIV-1 infected humans, indicating that extensive viral diversification in and of itself does not inevitably lead to AIDS. CONCLUSION: Positive diversifying selection in this natural reservoir host is the engine that has driven the evolution of the uniquely adaptable SIV/HIV envelope protein. These studies emphasize the importance of retroviral diversification within individual host reservoir animals as a critical substrate in facilitating cross-species transmission.",2006 Mar 20,"['Demma, LJ', 'Vanderford, TH', 'Logsdon, JM', 'Feinberg, MB', 'Staprans, SI']",Retrovirology,,,True
e7df6e6b00213948f60923cd0c111d58ffdfda00,PMC,Nonhuman Primate Models for SARS,http://dx.doi.org/10.1371/journal.pmed.0030194,PMC1435785,16608385,CC BY,Osterhaus and Haagmans discuss a new study in PLoS Medicine that supports the use of the cynomolgus macaque model to study SARS pathogenesis and to test intervention strategies.,2006 May 18,"['Haagmans, Bart L', 'Osterhaus, Albert D. M. E']",PLoS Med,,,True
c56ffdaf1cfbae5a6ed0abea495eaf7fa1cbc031,PMC,Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1371/journal.pmed.0030149,PMC1435788,16605302,CC0,"BACKGROUND: The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV. METHODS AND FINDINGS: In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain. CONCLUSIONS: SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.",2006 May 18,"['Lawler, James V', 'Endy, Timothy P', 'Hensley, Lisa E', 'Garrison, Aura', 'Fritz, Elizabeth A', 'Lesar, May', 'Baric, Ralph S', 'Kulesh, David A', 'Norwood, David A', 'Wasieloski, Leonard P', 'Ulrich, Melanie P', 'Slezak, Tom R', 'Vitalis, Elizabeth', 'Huggins, John W', 'Jahrling, Peter B', 'Paragas, Jason']",PLoS Med,,,True
4fc15d2af497369e0e7aa99dc78a403bdfa4790f,PMC,A Macaque Model of SARS,http://dx.doi.org/10.1371/journal.pmed.0030222,PMC1435789,,CC BY,,2006 May 18,,PLoS Med,,,True
51dd595e1404da9a49935f1df61c163b6ad01a58,PMC,Prions Adhere to Soil Minerals and Remain Infectious,http://dx.doi.org/10.1371/journal.ppat.0020032,PMC1435987,16617377,CC BY,"An unidentified environmental reservoir of infectivity contributes to the natural transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) in sheep, deer, and elk. Prion infectivity may enter soil environments via shedding from diseased animals and decomposition of infected carcasses. Burial of TSE-infected cattle, sheep, and deer as a means of disposal has resulted in unintentional introduction of prions into subsurface environments. We examined the potential for soil to serve as a TSE reservoir by studying the interaction of the disease-associated prion protein (PrP(Sc)) with common soil minerals. In this study, we demonstrated substantial PrP(Sc) adsorption to two clay minerals, quartz, and four whole soil samples. We quantified the PrP(Sc)-binding capacities of each mineral. Furthermore, we observed that PrP(Sc) desorbed from montmorillonite clay was cleaved at an N-terminal site and the interaction between PrP(Sc) and Mte was strong, making desorption of the protein difficult. Despite cleavage and avid binding, PrP(Sc) bound to Mte remained infectious. Results from our study suggest that PrP(Sc) released into soil environments may be preserved in a bioavailable form, perpetuating prion disease epizootics and exposing other species to the infectious agent.",2006 Apr 14,"['Johnson, Christopher J', 'Phillips, Kristen E', 'Schramm, Peter T', 'McKenzie, Debbie', 'Aiken, Judd M', 'Pedersen, Joel A']",PLoS Pathog,,,True
009eaad22ad509c7286b0aaa59b0751405b39d3a,PMC,Prions Adhere to Soil Minerals and Remain Infectious,http://dx.doi.org/10.1371/journal.ppat.0020032,PMC1435987,16617377,CC BY,"An unidentified environmental reservoir of infectivity contributes to the natural transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) in sheep, deer, and elk. Prion infectivity may enter soil environments via shedding from diseased animals and decomposition of infected carcasses. Burial of TSE-infected cattle, sheep, and deer as a means of disposal has resulted in unintentional introduction of prions into subsurface environments. We examined the potential for soil to serve as a TSE reservoir by studying the interaction of the disease-associated prion protein (PrP(Sc)) with common soil minerals. In this study, we demonstrated substantial PrP(Sc) adsorption to two clay minerals, quartz, and four whole soil samples. We quantified the PrP(Sc)-binding capacities of each mineral. Furthermore, we observed that PrP(Sc) desorbed from montmorillonite clay was cleaved at an N-terminal site and the interaction between PrP(Sc) and Mte was strong, making desorption of the protein difficult. Despite cleavage and avid binding, PrP(Sc) bound to Mte remained infectious. Results from our study suggest that PrP(Sc) released into soil environments may be preserved in a bioavailable form, perpetuating prion disease epizootics and exposing other species to the infectious agent.",2006 Apr 14,"['Johnson, Christopher J', 'Phillips, Kristen E', 'Schramm, Peter T', 'McKenzie, Debbie', 'Aiken, Judd M', 'Pedersen, Joel A']",PLoS Pathog,,,False
4fa871503ddbbaaead7a34fce89298a36648f662,PMC,Inhibition of cytokine gene expression and induction of chemokine genes in non-lymphatic cells infected with SARS coronavirus,http://dx.doi.org/10.1186/1743-422X-3-17,PMC1444920,16571117,CC BY,"BACKGROUND: SARS coronavirus (SARS-CoV) is the etiologic agent of the severe acute respiratory syndrome. SARS-CoV mainly infects tissues of non-lymphatic origin, and the cytokine profile of those cells can determine the course of disease. Here, we investigated the cytokine response of two human non-lymphatic cell lines, Caco-2 and HEK 293, which are fully permissive for SARS-CoV. RESULTS: A comparison with established cytokine-inducing viruses revealed that SARS-CoV only weakly triggered a cytokine response. In particular, SARS-CoV did not activate significant transcription of the interferons IFN-α, IFN-β, IFN-λ1, IFN-λ2/3, as well as of the interferon-induced antiviral genes ISG56 and MxA, the chemokine RANTES and the interleukine IL-6. Interestingly, however, SARS-CoV strongly induced the chemokines IP-10 and IL-8 in the colon carcinoma cell line Caco-2, but not in the embryonic kidney cell line 293. CONCLUSION: Our data indicate that SARS-CoV suppresses the antiviral cytokine system of non-immune cells to a large extent, thus buying time for dissemination in the host. However, synthesis of IP-10 and IL-8, which are established markers for acute-stage SARS, escapes the virus-induced silencing at least in some cell types. Therefore, the progressive infiltration of immune cells into the infected lungs observed in SARS patients could be due to the production of these chemokines by the infected tissue cells.",2006 Mar 29,"['Spiegel, Martin', 'Weber, Friedemann']",Virol J,,,True
acb6848d159dbf4970d1f76474a634110b3558e7,PMC,Heterologous expression of Brucella abortus GroEL heat-shock protein in Lactococcus lactis,http://dx.doi.org/10.1186/1475-2859-5-14,PMC1444932,16556312,CC BY,"BACKGROUND: Brucella abortus is a facultative intracellular pathogen that mainly infects cattle and humans. Current vaccines rely on live attenuated strains of B. abortus, which can revert to their pathogenic status and thus are not totally safe for use in humans. Therefore, the development of mucosal live vaccines using the food-grade lactic acid bacterium, Lactococcus lactis, as an antigen delivery vector, is an attractive alternative and a safer vaccination strategy against B. abortus. Here, we report the construction of L. lactis strains genetically modified to produce B. abortus GroEL heat-shock protein, a candidate antigen, in two cellular locations, intracellular or secreted. RESULTS: Only the secreted form of GroEL was stably produced in L. lactis, suggesting a detrimental effect of GroEL protein when intracellularly produced in this bacterium. Only trace amounts of mature GroEL were detected in the supernatant fraction of induced lactococcal cultures, and the GroEL precursor remained stacked in the cell fraction. Attempts to raise the secretion yields were made, but even when GroEL was fused to a synthetic propeptide, secretion of this antigen was not improved. CONCLUSION: We found that L. lactis is able to produce, and to secrete, a stable form of GroEL into the extracellular medium. Despite the low secretion efficiency of GroEL, which suggest that this antigen interacts with the cell envelope of L. lactis, secretion seems to be the best way to achieve both production and protein yields, regardless of cellular location. The L. lactis strain secreting GroEL has potential for in vivo immunization.",2006 Mar 23,"['Miyoshi, Anderson', 'Bermúdez-Humarán, Luis G', 'Ribeiro, Luciana A', 'Le Loir, Yves', 'Oliveira, Sérgio C', 'Langella, Philippe', 'Azevedo, Vasco']",Microb Cell Fact,,,True
4691c6219bc10483f3291813a98d4145c1876827,PMC,Delaying the International Spread of Pandemic Influenza,http://dx.doi.org/10.1371/journal.pmed.0030212,PMC1450020,16640458,CC BY,"BACKGROUND: The recent emergence of hypervirulent subtypes of avian influenza has underlined the potentially devastating effects of pandemic influenza. Were such a virus to acquire the ability to spread efficiently between humans, control would almost certainly be hampered by limited vaccine supplies unless global spread could be substantially delayed. Moreover, the large increases that have occurred in international air travel might be expected to lead to more rapid global dissemination than in previous pandemics. METHODS AND FINDINGS: To evaluate the potential of local control measures and travel restrictions to impede global dissemination, we developed stochastic models of the international spread of influenza based on extensions of coupled epidemic transmission models. These models have been shown to be capable of accurately forecasting local and global spread of epidemic and pandemic influenza. We show that under most scenarios restrictions on air travel are likely to be of surprisingly little value in delaying epidemics, unless almost all travel ceases very soon after epidemics are detected. CONCLUSIONS: Interventions to reduce local transmission of influenza are likely to be more effective at reducing the rate of global spread and less vulnerable to implementation delays than air travel restrictions. Nevertheless, under the most plausible scenarios, achievable delays are small compared with the time needed to accumulate substantial vaccine stocks.",2006 Jun 2,"['Cooper, Ben S', 'Pitman, Richard J', 'Edmunds, W. John', 'Gay, Nigel J']",PLoS Med,,,True
cda5efb9ec3966e7cd1df793ff55b51d9611eec3,PMC,Identifying strategies to improve access to credible and relevant information for public health professionals: a qualitative study,http://dx.doi.org/10.1186/1471-2458-6-89,PMC1456961,16597331,CC BY,"BACKGROUND: Movement towards evidence-based practices in many fields suggests that public health (PH) challenges may be better addressed if credible information about health risks and effective PH practices is readily available. However, research has shown that many PH information needs are unmet. In addition to reviewing relevant literature, this study performed a comprehensive review of existing information resources and collected data from two representative PH groups, focusing on identifying current practices, expressed information needs, and ideal systems for information access. METHODS: Nineteen individual interviews were conducted among employees of two domains in a state health department – communicable disease control and community health promotion. Subsequent focus groups gathered additional data on preferences for methods of information access and delivery as well as information format and content. Qualitative methods were used to identify themes in the interview and focus group transcripts. RESULTS: Informants expressed similar needs for improved information access including single portal access with a good search engine; automatic notification regarding newly available information; access to best practice information in many areas of interest that extend beyond biomedical subject matter; improved access to grey literature as well as to more systematic reviews, summaries, and full-text articles; better methods for indexing, filtering, and searching for information; and effective ways to archive information accessed. Informants expressed a preference for improving systems with which they were already familiar such as PubMed and listservs rather than introducing new systems of information organization and delivery. A hypothetical ideal model for information organization and delivery was developed based on informants' stated information needs and preferred means of delivery. Features of the model were endorsed by the subjects who reviewed it. CONCLUSION: Many critical information needs of PH practitioners are not being met efficiently or at all. We propose a dual strategy of: 1) promoting incremental improvements in existing information delivery systems based on the expressed preferences of the PH users of the systems and 2) the concurrent development and rigorous evaluation of new models of information organization and delivery that draw on successful resources already operating to deliver information to clinical medical practitioners.",2006 Apr 5,"['LaPelle, Nancy R', 'Luckmann, Roger', 'Simpson, E Hatheway', 'Martin, Elaine R']",BMC Public Health,,,True
a1b6c2b3b808e995697f94d9676d5d5c85180177,PMC,On pandemics and the duty to care: whose duty? who cares?,http://dx.doi.org/10.1186/1472-6939-7-5,PMC1459179,16626488,CC BY,"BACKGROUND: As a number of commentators have noted, SARS exposed the vulnerabilities of our health care systems and governance structures. Health care professionals (HCPs) and hospital systems that bore the brunt of the SARS outbreak continue to struggle with the aftermath of the crisis. Indeed, HCPs – both in clinical care and in public health – were severely tested by SARS. Unprecedented demands were placed on their skills and expertise, and their personal commitment to their profession was severely tried. Many were exposed to serious risk of morbidity and mortality, as evidenced by the World Health Organization figures showing that approximately 30% of reported cases were among HCPs, some of whom died from the infection. Despite this challenge, professional codes of ethics are silent on the issue of duty to care during communicable disease outbreaks, thus providing no guidance on what is expected of HCPs or how they ought to approach their duty to care in the face of risk. DISCUSSION: In the aftermath of SARS and with the spectre of a pandemic avian influenza, it is imperative that we (re)consider the obligations of HCPs for patients with severe infectious diseases, particularly diseases that pose risks to those providing care. It is of pressing importance that organizations representing HCPs give clear indication of what standard of care is expected of their members in the event of a pandemic. In this paper, we address the issue of special obligations of HCPs during an infectious disease outbreak. We argue that there is a pressing need to clarify the rights and responsibilities of HCPs in the current context of pandemic flu preparedness, and that these rights and responsibilities ought to be codified in professional codes of ethics. Finally, we present a brief historical accounting of the treatment of the duty to care in professional health care codes of ethics. SUMMARY: An honest and critical examination of the role of HCPs during communicable disease outbreaks is needed in order to provide guidelines regarding professional rights and responsibilities, as well as ethical duties and obligations. With this paper, we hope to open the social dialogue and advance the public debate on this increasingly urgent issue.",2006 Apr 20,"['Ruderman, Carly', 'Tracy, C Shawn', 'Bensimon, Cécile M', 'Bernstein, Mark', 'Hawryluck, Laura', 'Shaul, Randi Zlotnik', 'Upshur, Ross EG']",BMC Med Ethics,,,True
e8d81518d127913ce42b22fbdd96d416c4f82e44,PMC,Insertional protein engineering for analytical molecular sensing,http://dx.doi.org/10.1186/1475-2859-5-15,PMC1459189,16584558,CC BY,"The quantitative detection of low analyte concentrations in complex samples is becoming an urgent need in biomedical, food and environmental fields. Biosensors, being hybrid devices composed by a biological receptor and a signal transducer, represent valuable alternatives to non biological analytical instruments because of the high specificity of the biomolecular recognition. The vast range of existing protein ligands enable those macromolecules to be used as efficient receptors to cover a diversity of applications. In addition, appropriate protein engineering approaches enable further improvement of the receptor functioning such as enhancing affinity or specificity in the ligand binding. Recently, several protein-only sensors are being developed, in which either both the receptor and signal transducer are parts of the same protein, or that use the whole cell where the protein is produced as transducer. In both cases, as no further chemical coupling is required, the production process is very convenient. However, protein platforms, being rather rigid, restrict the proper signal transduction that necessarily occurs through ligand-induced conformational changes. In this context, insertional protein engineering offers the possibility to develop new devices, efficiently responding to ligand interaction by dramatic conformational changes, in which the specificity and magnitude of the sensing response can be adjusted up to a convenient level for specific analyte species. In this report we will discuss the major engineering approaches taken for the designing of such instruments as well as the relevant examples of resulting protein-only biosensors.",2006 Apr 3,"['Ferraz, Rosa María', 'Vera, Andrea', 'Arís, Anna', 'Villaverde, Antonio']",Microb Cell Fact,,,True
f38f3b112e4b702b60ba56be806d418bbb2b83c3,PMC,Immune Protection of Nonhuman Primates against Ebola Virus with Single Low-Dose Adenovirus Vectors Encoding Modified GPs,http://dx.doi.org/10.1371/journal.pmed.0030177,PMC1459482,16683867,CC0,"BACKGROUND: Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or replication-defective adenoviral vectors (rAd) encoding the Ebola glycoprotein (GP) and nucleoprotein (NP) has been previously shown to confer specific protective immunity in nonhuman primates. GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine. METHODS AND FINDINGS: To address this question, we have explored the efficacy of mutant GPs from multiple Ebola virus strains with reduced in vitro cytopathicity and analyzed their protective effects in the primate challenge model, with or without NP. Deletion of the GP transmembrane domain eliminated in vitro cytopathicity but reduced its protective efficacy by at least one order of magnitude. In contrast, a point mutation was identified that abolished this cytopathicity but retained immunogenicity and conferred immune protection in the absence of NP. The minimal effective rAd dose was established at 10(10) particles, two logs lower than that used previously. CONCLUSIONS: Expression of specific GPs alone vectored by rAd are sufficient to confer protection against lethal challenge in a relevant nonhuman primate model. Elimination of NP from the vaccine and dose reductions to 10(10) rAd particles do not diminish protection and simplify the vaccine, providing the basis for selection of a human vaccine candidate.",2006 Jun 16,"['Sullivan, Nancy J', 'Geisbert, Thomas W', 'Geisbert, Joan B', 'Shedlock, Devon J', 'Xu, Ling', 'Lamoreaux, Laurie', 'Custers, Jerome H. H. V', 'Popernack, Paul M', 'Yang, Zhi-Yong', 'Pau, Maria G', 'Roederer, Mario', 'Koup, Richard A', 'Goudsmit, Jaap', 'Jahrling, Peter B', 'Nabel, Gary J']",PLoS Med,,,True
2e2de8d6ebd368c062fed5770aa26a780bdc25b8,PMC,The interferon gamma gene polymorphism +874 A/T is associated with severe acute respiratory syndrome,http://dx.doi.org/10.1186/1471-2334-6-82,PMC1468415,16672072,CC BY,"BACKGROUND: Cytokines play important roles in antiviral action. We examined whether polymorphisms of IFN-γ,TNF-α and IL-10 affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). METHODS: A case-control study was carried out in 476 Chinese SARS patients and 449 healthy controls. We tested the polymorphisms of IFN-γ,TNF-α and IL-10 for their associations with SARS. RESULTS: IFN-γ +874A allele was associated with susceptibility to SARS in a dose-dependent manner (P < 0.001). Individuals with IFN-γ +874 AA and AT genotype had a 5.19-fold (95% Confidence Interval [CI], 2.78-9.68) and 2.57-fold (95% CI, 1.35-4.88) increased risk of developing SARS respectively. The polymorphisms of IL-10 and TNF-α were not associated with SARS susceptibility. CONCLUSION: IFN-γ +874A allele was shown to be a risk factor in SARS susceptibility.",2006 May 4,"['Chong, Wai Po', 'Ip, WK Eddie', 'Tso, Gloria Hoi Wan', 'Ng, Man Wai', 'Wong, Wilfred Hing Sang', 'Law, Helen Ka Wai', 'Yung, Raymond WH', 'Chow, Eudora Y', 'Au, KL', 'Chan, Eric YT', 'Lim, Wilina', 'Peiris, JS Malik', 'Lau, Yu Lung']",BMC Infect Dis,,,True
dce2c9d835e3ebbee3ff4e6868d5755ddec76b71,PMC,Microarray-based identification of antigenic variants of foot-and-mouth disease virus: a bioinformatics quality assessment,http://dx.doi.org/10.1186/1471-2164-7-117,PMC1481559,16709242,CC BY,"BACKGROUND: The evolution of viral quasispecies can influence viral pathogenesis and the response to antiviral treatments. Mutant clouds in infected organisms represent the first stage in the genetic and antigenic diversification of RNA viruses, such as foot and mouth disease virus (FMDV), an important animal pathogen. Antigenic variants of FMDV have been classically diagnosed by immunological or RT-PCR-based methods. DNA microarrays are becoming increasingly useful for the analysis of gene expression and single nucleotide polymorphisms (SNPs). Recently, a FMDV microarray was described to detect simultaneously the seven FMDV serotypes. These results encourage the development of new oligonucleotide microarrays to probe the fine genetic and antigenic composition of FMDV for diagnosis, vaccine design, and to gain insight into the molecular epidemiology of this pathogen. RESULTS: A FMDV microarray was designed and optimized to detect SNPs at a major antigenic site of the virus. A screening of point mutants of the genomic region encoding antigenic site A of FMDV C-S8c1 was achieved. The hybridization pattern of a mutant includes specific positive and negative signals as well as crosshybridization signals, which are of different intensity depending on the thermodynamic stability of each probe-target pair. Moreover, an array bioinformatic classification method was developed to evaluate the hybridization signals. This statistical analysis shows that the procedure allows a very accurate classification per variant genome. CONCLUSION: A specific approach based on a microarray platform aimed at distinguishing point mutants within an important determinant of antigenicity and host cell tropism, namely the G-H loop of capsid protein VP1, was developed. The procedure is of general applicability as a test for specificity and discriminatory power of microarray-based diagnostic procedures using multiple oligonucleotide probes.",2006 May 18,"['Martín, Verónica', 'Perales, Celia', 'Abia, David', 'Ortíz, Angel R', 'Domingo, Esteban', 'Briones, Carlos']",BMC Genomics,,,True
babad3896fca8ed7c89d9b785c08e7c42a48a6a2,PMC,Markers of exacerbation severity in chronic obstructive pulmonary disease,http://dx.doi.org/10.1186/1465-9921-7-74,PMC1481583,16686949,CC BY,"BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) can experience 'exacerbations' of their conditions. An exacerbation is an event defined in terms of subjective descriptors or symptoms, namely dyspnoea, cough and sputum that worsen sufficiently to warrant a change in medical management. There is a need for reliable markers that reflect the pathological mechanisms that underlie exacerbation severity and that can be used as a surrogate to assess treatment effects in clinical studies. Little is known as to how existing study variables and suggested markers change in both the stable and exacerbation phases of COPD. In an attempt to find the best surrogates for exacerbations, we have reviewed the literature to identify which of these markers change in a consistent manner with the severity of the exacerbation event. METHODS: We have searched standard databases between 1966 to July 2004 using major keywords and terms. Studies that provided demographics, spirometry, potential markers, and clear eligibility criteria were included in this study. Central tendencies and dispersions for all the variables and markers reported and collected by us were first tabulated according to sample size and ATS/ERS 2004 Exacerbation Severity Levels I to III criteria. Due to the possible similarity of patients in Levels II and III, the data was also redefined into categories of exacerbations, namely out-patient (Level I) and in-patient (Levels II & III combined). For both approaches, we performed a fixed effect meta-analysis on each of the reported variables. RESULTS: We included a total of 268 studies reported between 1979 to July 2004. These studies investigated 142,407 patients with COPD. Arterial carbon dioxide tension and breathing rate were statistically different between all levels of exacerbation severity and between in out- and in-patient settings. Most other measures showed weak relationships with either level or setting, or they had insufficient data to permit meta-analysis. CONCLUSION: Arterial carbon dioxide and breathing rate varied in a consistent manner with exacerbation severity and patient setting. Many other measures showed weak correlations that should be further explored in future longitudinal studies or assessed using suggested mathematical modelling techniques.",2006 May 10,"['Franciosi, Luigi G', 'Page, Clive P', 'Celli, Bartolome R', 'Cazzola, Mario', 'Walker, Michael J', 'Danhof, Meindert', 'Rabe, Klaus F', 'Pasqua, Oscar E Della']",Respir Res,,,True
be57ba746b8fec268025df6afc68536fbd0188d8,PMC,In vitro inhibition of human influenza A virus replication by chloroquine,http://dx.doi.org/10.1186/1743-422X-3-39,PMC1481635,16729896,CC BY,"Chloroquine is a 9-aminoquinolone with well-known anti-malarial effects. It has biochemical properties that could be applied to inhibit viral replication. We report here that chloroquine is able to inhibit influenza A virus replication, in vitro, and the IC50s of chloroquine against influenza A viruses H1N1 and H3N2 are lower than the plasma concentrations reached during treatment of acute malaria. The potential of chloroquine to be added to the limited range of anti-influenza drugs should be explored further, particularly since antiviral drugs play a vital role in influenza pandemic preparedness.",2006 May 29,"['Ooi, Eng Eong', 'Chew, Janet Seok Wei', 'Loh, Jin Phang', 'Chua, Robert CS']",Virol J,,,True
8095e2bbc38cfeb18180deca4796293f5ce24eae,PMC,Amphotropic murine leukemia virus is preferentially attached to cholesterol-rich microdomains after binding to mouse fibroblasts,http://dx.doi.org/10.1186/1743-422X-3-21,PMC1483818,16579862,CC BY,"BACKGROUND: We have recently shown that amphotropic murine leukemia virus (A-MLV) can enter the mouse fibroblast cell line NIH3T3 via caveola-dependent endocytosis. But due to the size and omega-like shape of caveolae it is possible that A-MLV initially binds cells outside of caveolae. Rafts have been suggested to be pre-caveolae and we here investigate whether A-MLV initially binds to its receptor Pit2, a sodium-dependent phosphate transporter, in rafts or caveolae or outside these cholesterol-rich microdomains. RESULTS: Here, we show that a high amount of cell-bound A-MLV was attached to large rafts of NIH3T3 at the time of investigation. These large rafts were not enriched in caveolin-1, a major structural component of caveolae. In addition, they are rather of natural occurrence in NIH3T3 cells than a result of patching of smaller rafts by A-MLV. Thus cells incubated in parallel with vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped MLV particles showed the same pattern of large rafts as cells incubated with A-MLV, but VSV-G pseudotyped MLV particles did not show any preference to attach to these large microdomains. CONCLUSION: The high concentration of A-MLV particles bound to large rafts of NIH3T3 cells suggests a role of these microdomains in early A-MLV binding events.",2006 Apr 2,"['Beer, Christiane', 'Pedersen, Lene']",Virol J,,,True
3650b941642ddc9c3627fdb8d415f8c8b69a4158,PMC,Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape Mutants,http://dx.doi.org/10.1371/journal.pmed.0030237,PMC1483912,16796401,CC BY,"BACKGROUND: Experimental animal data show that protection against severe acute respiratory syndrome coronavirus (SARS-CoV) infection with human monoclonal antibodies (mAbs) is feasible. For an effective immune prophylaxis in humans, broad coverage of different strains of SARS-CoV and control of potential neutralization escape variants will be required. Combinations of virus-neutralizing, noncompeting mAbs may have these properties. METHODS AND FINDINGS: Human mAb CR3014 has been shown to completely prevent lung pathology and abolish pharyngeal shedding of SARS-CoV in infected ferrets. We generated in vitro SARS-CoV variants escaping neutralization by CR3014, which all had a single P462L mutation in the glycoprotein spike (S) of the escape virus. In vitro experiments confirmed that binding of CR3014 to a recombinant S fragment (amino acid residues 318–510) harboring this mutation was abolished. We therefore screened an antibody-phage library derived from blood of a convalescent SARS patient for antibodies complementary to CR3014. A novel mAb, CR3022, was identified that neutralized CR3014 escape viruses, did not compete with CR3014 for binding to recombinant S1 fragments, and bound to S1 fragments derived from the civet cat SARS-CoV-like strain SZ3. No escape variants could be generated with CR3022. The mixture of both mAbs showed neutralization of SARS-CoV in a synergistic fashion by recognizing different epitopes on the receptor-binding domain. Dose reduction indices of 4.5 and 20.5 were observed for CR3014 and CR3022, respectively, at 100% neutralization. Because enhancement of SARS-CoV infection by subneutralizing antibody concentrations is of concern, we show here that anti-SARS-CoV antibodies do not convert the abortive infection of primary human macrophages by SARS-CoV into a productive one. CONCLUSIONS: The combination of two noncompeting human mAbs CR3014 and CR3022 potentially controls immune escape and extends the breadth of protection. At the same time, synergy between CR3014 and CR3022 may allow for a lower total antibody dose to be administered for passive immune prophylaxis of SARS-CoV infection.",2006 Jul 4,"['ter Meulen, Jan', 'van den Brink, Edward N', 'Poon, Leo L. M', 'Marissen, Wilfred E', 'Leung, Cynthia S. W', 'Cox, Freek', 'Cheung, Chung Y', 'Bakker, Arjen Q', 'Bogaards, Johannes A', 'van Deventer, Els', 'Preiser, Wolfgang', 'Doerr, Hans Wilhelm', 'Chow, Vincent T', 'de Kruif, John', 'Peiris, Joseph S. M', 'Goudsmit, Jaap']",PLoS Med,,,True
8c640872048570b0a671ec08c83ef6cbebcdd78e,PMC,Selection of a set of reliable reference genes for quantitative real-time PCR in normal equine skin and in equine sarcoids,http://dx.doi.org/10.1186/1472-6750-6-24,PMC1484482,16643647,CC BY,"BACKGROUND: Real-time quantitative PCR can be a very powerful and accurate technique to examine gene transcription patterns in different biological conditions. One of the critical steps in comparing transcription profiles is accurate normalisation. In most of the studies published on real-time PCR in horses, normalisation occurred against only one reference gene, usually GAPDH or ACTB, without validation of its expression stability. This might result in unreliable conclusions, because it has been demonstrated that the expression levels of so called ""housekeeping genes"" may vary considerably in different tissues, cell types or disease stages, particularly in clinical samples associated with malignant disease. The goal of this study was to establish a reliable set of reference genes for studies concerning normal equine skin and equine sarcoids, which are the most common skin tumour in horses. RESULTS: In the present study the gene transcription levels of 6 commonly used reference genes (ACTB, B2M, HPRT1, UBB, TUBA1 and RPL32) were determined in normal equine skin and in equine sarcoids. After applying the geNorm applet to this set of genes, TUBA1, ACTB and UBB were found to be most stable in normal skin and B2M, ACTB and UBB in equine sarcoids. CONCLUSION: Based on these results, TUBA1, ACTB and UBB, respectively B2M, ACTB and UBB can be proposed as reference gene panels for accurate normalisation of quantitative data for normal equine skin, respectively equine sarcoids. When normal skin and equine sarcoids are compared, the use of the geometric mean of UBB, ACTB and B2M can be recommended as a reliable and accurate normalisation factor.",2006 Apr 27,"['Bogaert, Lies', 'Van Poucke, Mario', 'De Baere, Cindy', 'Peelman, Luc', 'Gasthuys, Frank', 'Martens, Ann']",BMC Biotechnol,,,True
b1f86a8d26afcb49621b2b3aba8eaf1851b95315,PMC,Combined fluticasone propionate and salmeterol reduces RSV infection more effectively than either of them alone in allergen-sensitized mice,http://dx.doi.org/10.1186/1743-422X-3-32,PMC1488829,16719922,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in infants and is a risk factor for the development of asthma. Allergic asthmatics are more susceptible to RSV infection and viral exacerbation. METHODS: Since the effectiveness of corticosteroids in treating RSV infection has been controversial, we tested fluticasone propionate (FP) and salmeterol (Sal) alone versus FP plus Sal (FPS) on RSV-induced airway inflammation. Mice were sensitized and challenged with ovalbumin (OVA) and infected with RSV. Following infection they were treated with FP, Sal, or FPS intranasally and airway hyperreactivity (AHR), inflammation and RSV titers were examined. RESULTS: The group treated with FPS showed significantly lower AHR compared to the group treated with FP or Sal alone. The group treated with FP alone showed slightly decreased (non-significant) AHR compared to controls. Treatment with FPS resulted in significant decreases in the percentage of eosinophils and neutrophils in bronchoalveolar lavage fluid and in lung pathology compared to FP or Sal. FP alone decreased eosinophils but not neutrophils or lymphocytes, while Sal alone decreased eosinophils and neutrophils but not lymphocytes. FPS treatment of mice infected with RSV in the absence of allergen sensitization resulted in a 50% decrease of RSV titer in the lung and a reduction in neutrophils compared to FP or Sal. CONCLUSION: Together, these results indicate that fluticasone in combination with salmeterol is a more effective treatment for decreasing airway hyperreactivity and inflammation than either of them alone in allergen-sensitized, RSV-infected mice.",2006 May 23,"['Singam, Rajeswari', 'Jena, Prasanna K', 'Behera, Sumita', 'Hellermann, Gary R', 'Lockey, Richard F', 'Ledford, Dennis', 'Mohapatra, Shyam S']",Virol J,,,True
a0f13b751004e29186fa070fdffa2e876815e41a,PMC,"Antibiotic resistance as a global threat: Evidence from China, Kuwait and the United States",http://dx.doi.org/10.1186/1744-8603-2-6,PMC1502134,16603071,CC BY,"BACKGROUND: Antimicrobial resistance is an under-appreciated threat to public health in nations around the globe. With globalization booming, it is important to understand international patterns of resistance. If countries already experience similar patterns of resistance, it may be too late to worry about international spread. If large countries or groups of countries that are likely to leap ahead in their integration with the rest of the world – China being the standout case – have high and distinctive patterns of resistance, then a coordinated response could substantially help to control the spread of resistance. The literature to date provides only limited evidence on these issues. METHODS: We study the recent patterns of antibiotic resistance in three geographically separated, and culturally and economically distinct countries – China, Kuwait and the United States – to gauge the range and depth of this global health threat, and its potential for growth as globalization expands. Our primary measures are the prevalence of resistance of specific bacteria to specific antibiotics. We also propose and illustrate methods for aggregating specific ""bug-drug"" data. We use these aggregate measures to summarize the resistance pattern for each country and to study the extent of correlation between countries' patterns of drug resistance. RESULTS: We find that China has the highest level of antibiotic resistance, followed by Kuwait and the U.S. In a study of resistance patterns of several most common bacteria in China in 1999 and 2001, the mean prevalence of resistance among hospital-acquired infections was as high as 41% (with a range from 23% to 77%) and that among community- acquired infections was 26% (with a range from 15% to 39%). China also has the most rapid growth rate of resistance (22% average growth in a study spanning 1994 to 2000). Kuwait is second (17% average growth in a period from 1999 to 2003), and the U.S. the lowest (6% from 1999 to 2002). Patterns of resistance across the three countries are not highly correlated; the most correlated were China and Kuwait, followed by Kuwait and the U.S., and the least correlated pair was China and the U.S. CONCLUSION: Antimicrobial resistance is a serious and growing problem in all three countries. To date, there is not strong international convergence in the countries' resistance patterns. This finding may change with the greater international travel that will accompany globalization. Future research on the determinants of drug resistance patterns, and their international convergence or divergence, should be a priority.",2006 Apr 7,"['Zhang, Ruifang', 'Eggleston, Karen', 'Rotimi, Vincent', 'Zeckhauser, Richard J']",Global Health,,,True
8b86e36ed4cc2b952e49ea978844332007c00439,PMC,The basic principles of migration health: Population mobility and gaps in disease prevalence,http://dx.doi.org/10.1186/1742-7622-3-3,PMC1513225,16674820,CC BY,"Currently, migrants and other mobile individuals, such as migrant workers and asylum seekers, are an expanding global population of growing social, demographic and political importance. Disparities often exist between a migrant population's place of origin and its destination, particularly with relation to health determinants. The effects of those disparities can be observed at both individual and population levels. Migration across health and disease disparities influences the epidemiology of certain diseases globally and in nations receiving migrants. While specific disease-based outcomes may vary between migrant group and location, general epidemiological principles may be applied to any situation where numbers of individuals move between differences in disease prevalence. Traditionally, migration health activities have been designed for national application and lack an integrated international perspective. Present and future health challenges related to migration may be more effectively addressed through collaborative global undertakings. This paper reviews the epidemiological relationships resulting from health disparities bridged by migration and describes the growing role of migration and population mobility in global disease epidemiology. The implications for national and international health policy and program planning are presented.",2006 May 4,"['Gushulak, Brian D', 'MacPherson, Douglas W']",Emerg Themes Epidemiol,,,True
362f9e6b508a42ffebfd1a95d146955d59c7cea0,PMC,Quantitative prediction of mouse class I MHC peptide binding affinity using support vector machine regression (SVR) models,http://dx.doi.org/10.1186/1471-2105-7-182,PMC1513606,16579851,CC BY,"BACKGROUND: The binding between peptide epitopes and major histocompatibility complex proteins (MHCs) is an important event in the cellular immune response. Accurate prediction of the binding between short peptides and the MHC molecules has long been a principal challenge for immunoinformatics. Recently, the modeling of MHC-peptide binding has come to emphasize quantitative predictions: instead of categorizing peptides as ""binders"" or ""non-binders"" or as ""strong binders"" and ""weak binders"", recent methods seek to make predictions about precise binding affinities. RESULTS: We developed a quantitative support vector machine regression (SVR) approach, called SVRMHC, to model peptide-MHC binding affinities. As a non-linear method, SVRMHC was able to generate models that out-performed existing linear models, such as the ""additive method"". By adopting a new ""11-factor encoding"" scheme, SVRMHC takes into account similarities in the physicochemical properties of the amino acids constituting the input peptides. When applied to MHC-peptide binding data for three mouse class I MHC alleles, the SVRMHC models produced more accurate predictions than those produced previously. Furthermore, comparisons based on Receiver Operating Characteristic (ROC) analysis indicated that SVRMHC was able to out-perform several prominent methods in identifying strongly binding peptides. CONCLUSION: As a method with demonstrated performance in the quantitative modeling of MHC-peptide binding and in identifying strong binders, SVRMHC is a promising immunoinformatics tool with not inconsiderable future potential.",2006 Mar 31,"['Liu, Wen', 'Meng, Xiangshan', 'Xu, Qiqi', 'Flower, Darren R', 'Li, Tongbin']",BMC Bioinformatics,,,True
4485f96496a208b7e77c9f53a8feb468483776db,PMC,Silencing Viral Infection,http://dx.doi.org/10.1371/journal.pmed.0030242,PMC1518680,16848617,CC BY,The authors describe recent progress and obstacles to harnessing RNA interference to prevent or treat viral infection.,2006 Jul 25,"['Dykxhoorn, Derek M', 'Lieberman, Judy']",PLoS Med,,,True
4db3931c4b24ae432d68b7e24f593b1272445523,PMC,Differentially profiling the low-expression transcriptomes of human hepatoma using a novel SSH/microarray approach,http://dx.doi.org/10.1186/1471-2164-7-131,PMC1522022,16737534,CC BY,"BACKGROUND: The main limitation in performing genome-wide gene-expression profiling is the assay of low-expression genes. Approaches with high throughput and high sensitivity for assaying low-expression transcripts are urgently needed for functional genomic studies. Combination of the suppressive subtractive hybridization (SSH) and cDNA microarray techniques using the subtracted cDNA clones as probes printed on chips has greatly improved the efficiency for fishing out the differentially expressed clones and has been used before. However, it remains tedious and inefficient sequencing works for identifying genes including the great number of redundancy in the subtracted amplicons, and sacrifices the original advantages of high sensitivity of SSH in profiling low-expression transcriptomes. RESULTS: We modified the previous combination of SSH and microarray methods by directly using the subtracted amplicons as targets to hybridize the pre-made cDNA microarrays (named as ""SSH/microarray""). mRNA prepared from three pairs of hepatoma and non-hepatoma liver tissues was subjected to the SSH/microarray assays, as well as directly to regular cDNA microarray assays for comparison. As compared to the original SSH and microarray combination assays, the modified SSH/microarray assays allowed for much easier inspection of the subtraction efficiency and identification of genes in the subtracted amplicons without tedious and inefficient sequencing work. On the other hand, 5015 of the 9376 genes originally filtered out by the regular cDNA microarray assays because of low expression became analyzable by the SSH/microarray assays. Moreover, the SSH/microarray assays detected about ten times more (701 vs. 69) HCC differentially expressed genes (at least a two-fold difference and P < 0.01), particularly for those with rare transcripts, than did the regular cDNA microarray assays. The differential expression was validated in 9 randomly selected genes in 18 pairs of hepatoma/non-hepatoma liver tissues using quantitative RT-PCR. The SSH/microarray approaches resulted in identifying many differentially expressed genes implicated in the regulation of cell cycle, cell death, signal transduction and cell morphogenesis, suggesting the involvement of multi-biological processes in hepato-carcinogenesis. CONCLUSION: The modified SSH/microarray approach is a simple but high-sensitive and high-efficient tool for differentially profiling the low-expression transcriptomes. It is most adequate for applying to functional genomic studies.",2006 May 31,"['Pan, Yi-Shin', 'Lee, Yun-Shien', 'Lee, Yung-Lin', 'Lee, Wei-Chen', 'Hsieh, Sen-Yung']",BMC Genomics,,,True
dfddc7262329261ef41c6da4bd8a56ec2c3f81dc,PMC,Differentially profiling the low-expression transcriptomes of human hepatoma using a novel SSH/microarray approach,http://dx.doi.org/10.1186/1471-2164-7-131,PMC1522022,16737534,CC BY,"BACKGROUND: The main limitation in performing genome-wide gene-expression profiling is the assay of low-expression genes. Approaches with high throughput and high sensitivity for assaying low-expression transcripts are urgently needed for functional genomic studies. Combination of the suppressive subtractive hybridization (SSH) and cDNA microarray techniques using the subtracted cDNA clones as probes printed on chips has greatly improved the efficiency for fishing out the differentially expressed clones and has been used before. However, it remains tedious and inefficient sequencing works for identifying genes including the great number of redundancy in the subtracted amplicons, and sacrifices the original advantages of high sensitivity of SSH in profiling low-expression transcriptomes. RESULTS: We modified the previous combination of SSH and microarray methods by directly using the subtracted amplicons as targets to hybridize the pre-made cDNA microarrays (named as ""SSH/microarray""). mRNA prepared from three pairs of hepatoma and non-hepatoma liver tissues was subjected to the SSH/microarray assays, as well as directly to regular cDNA microarray assays for comparison. As compared to the original SSH and microarray combination assays, the modified SSH/microarray assays allowed for much easier inspection of the subtraction efficiency and identification of genes in the subtracted amplicons without tedious and inefficient sequencing work. On the other hand, 5015 of the 9376 genes originally filtered out by the regular cDNA microarray assays because of low expression became analyzable by the SSH/microarray assays. Moreover, the SSH/microarray assays detected about ten times more (701 vs. 69) HCC differentially expressed genes (at least a two-fold difference and P < 0.01), particularly for those with rare transcripts, than did the regular cDNA microarray assays. The differential expression was validated in 9 randomly selected genes in 18 pairs of hepatoma/non-hepatoma liver tissues using quantitative RT-PCR. The SSH/microarray approaches resulted in identifying many differentially expressed genes implicated in the regulation of cell cycle, cell death, signal transduction and cell morphogenesis, suggesting the involvement of multi-biological processes in hepato-carcinogenesis. CONCLUSION: The modified SSH/microarray approach is a simple but high-sensitive and high-efficient tool for differentially profiling the low-expression transcriptomes. It is most adequate for applying to functional genomic studies.",2006 May 31,"['Pan, Yi-Shin', 'Lee, Yun-Shien', 'Lee, Yung-Lin', 'Lee, Wei-Chen', 'Hsieh, Sen-Yung']",BMC Genomics,,,False
7aac0f55c8b869e13f1c2678207430bc9203d65e,PMC,Design of microarray probes for virus identification and detection of emerging viruses at the genus level,http://dx.doi.org/10.1186/1471-2105-7-232,PMC1523220,16643672,CC BY,"BACKGROUND: Most virus detection methods are geared towards the detection of specific single viruses or just a few known targets, and lack the capability to uncover the novel viruses that cause emerging viral infections. To address this issue, we developed a computational method that identifies the conserved viral sequences at the genus level for all viral genomes available in GenBank, and established a virus probe library. The virus probes are used not only to identify known viruses but also for discerning the genera of emerging or uncharacterized ones. RESULTS: Using the microarray approach, the identity of the virus in a test sample is determined by the signals of both genus and species-specific probes. The genera of emerging and uncharacterized viruses are determined based on hybridization of the viral sequences to the conserved probes for the existing viral genera. A detection and classification procedure to determine the identity of a virus directly from detection signals results in the rapid identification of the virus. CONCLUSION: We have demonstrated the validity and feasibility of the above strategy with a small number of viral samples. The probe design algorithm can be applied to any publicly available viral sequence database. The strategy of using separate genus and species probe sets enables the use of a straightforward virus identity calculation directly based on the hybridization signals. Our virus identification strategy has great potential in the diagnosis of viral infections. The virus genus and specific probe database and the associated summary tables are available at",2006 Apr 28,"['Chou, Cheng-Chung', 'Lee, Te-Tsui', 'Chen, Chun-Houh', 'Hsiao, Hsiang-Yun', 'Lin, Yi-Ling', 'Ho, Mei-Shang', 'Yang, Pan-Chyr', 'Peck, Konan']",BMC Bioinformatics,,,True
40500cd7ae5b4e116e8b13e5408e7dfd96d43ab4,PMC,"From Functional Genomics to Functional Immunomics: New Challenges, Old Problems, Big Rewards",http://dx.doi.org/10.1371/journal.pcbi.0020081,PMC1523295,16863395,CC BY,"The development of DNA microarray technology a decade ago led to the establishment of functional genomics as one of the most active and successful scientific disciplines today. With the ongoing development of immunomic microarray technology—a spatially addressable, large-scale technology for measurement of specific immunological response—the new challenge of functional immunomics is emerging, which bears similarities to but is also significantly different from functional genomics. Immunonic data has been successfully used to identify biological markers involved in autoimmune diseases, allergies, viral infections such as human immunodeficiency virus (HIV), influenza, diabetes, and responses to cancer vaccines. This review intends to provide a coherent vision of this nascent scientific field, and speculate on future research directions. We discuss at some length issues such as epitope prediction, immunomic microarray technology and its applications, and computation and statistical challenges related to functional immunomics. Based on the recent discovery of regulation mechanisms in T cell responses, we envision the use of immunomic microarrays as a tool for advances in systems biology of cellular immune responses, by means of immunomic regulatory network models.",2006 Jul 28,"['Braga-Neto, Ulisses M', 'Marques, Ernesto T. A']",PLoS Comput Biol,,,True
48d2cdd1975a60aa6d7ab15b51b523b10529b038,PMC,The role of single N-glycans in proteolytic processing and cell surface transport of the Lassa virus glycoprotein GP-C,http://dx.doi.org/10.1186/1743-422X-3-41,PMC1524727,16737539,CC BY,"Lassa virus glycoprotein is synthesised as a precursor (preGP-C) into the lumen of the endoplasmic reticulum. After cotranslational cleavage of the signal peptide, the immature GP-C is posttranslationally processed into the N-terminal subunit GP-1 and the C-terminal subunit GP-2 by the host cell subtilase SKI-1/S1P. The glycoprotein precursor contains eleven potential N-glycosylation sites. In this report, we investigated the effect of each N-glycan on proteolytic cleavage and cell surface transport by disrupting the consensus sequences of eleven potential N-glycan attachment sites individually. Five glycoprotein mutants with disrupted N-glycosylation sites were still proteolytically processed, whereas the remaining N-glycosylation sites are necessary for GP-C cleavage. Despite the lack of proteolytic processing, all cleavage-defective mutants were transported to the cell surface and remained completely endo H-sensitive. The findings indicate that N-glycans are needed for correct conformation of GP-C in order to be cleaved by SKI-1/S1P.",2006 May 31,"['Eichler, Robert', 'Lenz, Oliver', 'Garten, Wolfgang', 'Strecker, Thomas']",Virol J,,,True
fafa45b4080e37b2d37450168738d991a0399343,PMC,"The synergistic effect of IFN-α and IFN-γ against HSV-2 replication in Vero cells is not interfered by the plant antiviral 1-cinnamoyl-3, 11-dihydroxymeliacarpin",http://dx.doi.org/10.1186/1743-422X-3-45,PMC1525181,16772029,CC BY,"BACKGROUND: Recent studies have shown that gamma interferon (IFN-γ) synergizes with IFN-α/β to inhibit herpes simplex virus type 1 (HSV-1) replication in vitro. Since IFN response represents an early host defense event against viral infection and the fact that treatment with meliacine, a plant antiviral, ameliorate the severity of the herpetic infection in female mice infected intravaginally with HSV-2, we wanted to investigate whether the administration of meliacine to HSV-2 infected mice could altered the homoestasis of IFNs host response. For this purpose we studied the effect of the compound 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), which is the responsible for meliacine antiviral action, on the HSV-2 inhibition exerted by IFN α, IFN-γ or their combination. RESULTS: We have found that like HSV-1, IFN-γ synergizes with IFN-α to inhibit HSV-2 replication in Vero cells. While treatment with IFN-α or IFN-γ alone has weak antiviral action, HSV-2 plaque formation, viral replication and the onset of viral CPE in Vero cells are synergistically inhibited by interferon combination. In addition, CDM treatment contributes to protect cells from virus cytopathic effect and causes a strong inhibition of HSV-2 titer. Moreover, the presence of CDM for 2 h before IFN induction, during the 16 h induction period, only for 24 h after infection or during the complete IFN treatment period, reduces virus yields in an additive way without affecting IFN antiviral action. CONCLUSION: The results reported here indicated that the presence of CDM did not alter the antiviral activity of IFN-α, IFN-γ or the synergism exerted by their combination. As a result we can envision that the administration of CDM in vivo could not affect the biological activity of IFNs, which are so important mediators of the innate resistance to HSV-2 infection.",2006 Jun 13,"['Petrera, Erina', 'Coto, Celia E']",Virol J,,,True
02b8dea56378d11fe92d6a60ff37a34b0d6ea63e,PMC,CD147 overexpression on synoviocytes in rheumatoid arthritis enhances matrix metalloproteinase production and invasiveness of synoviocytes,http://dx.doi.org/10.1186/ar1899,PMC1526600,16507143,CC BY,"Macrophage-like synoviocytes and fibroblast-like synoviocytes (FLS) are known as the most active cells of rheumatoid arthritis (RA) and are close to the articular cartilage in a position enabling them to invade the cartilage. Macrophage-like synoviocytes and FLS expression of matrix metalloproteinases (MMPs) and their interaction has aroused great interest. The present article studied the expression of CD147, also called extracellular matrix metalloproteinase inducer, on monocytes/macrophages and FLS from RA patients and its potential role in enhancing MMPs and the invasiveness of synoviocytes. Expression of CD147 on FLS derived from RA patients and from osteoarthritis patients, and expression of CD147 on monocytes/macrophages from rheumatic synovial fluid and healthy peripheral blood were analyzed by flow cytometry. The levels of CD147, MMP-2 and MMP-9 mRNA in FLS were detected by RT-PCR. The role of CD147 in MMP production and the cells' invasiveness in vitro were studied by the co-culture of FLS with the human THP-1 cell line or monocytes/macrophages, by gel zymography and by invasion assay. The results showed that the expression of CD147 was higher on RA FLS than on osteoarthritis FLS and was higher on monocytes/macrophages from rheumatic synovial fluid than on monocytes/macrophages from healthy peripheral blood. RT-PCR showed that the expressions of CD147, MMP-2 and MMP-9 mRNA was higher in RA FLS than in osteoarthritis FLS. A significantly elevated secretion and activation of MMP-2 and MMP-9 were observed in RA FLS co-cultured with differentiated THP-1 cells or RA synovial monocytes/macrophages, compared with those co-cultured with undifferentiated THP-1 cells or healthy control peripheral blood monocytes. Invasion assays showed an increased number of invading cells in the co-cultured RA FLS with differentiated THP-1 cells or RA synovial monocytes/macrophages. CD147 antagonistic peptide inhibited the MMP production and the invasive potential. Our studies demonstrated that the CD147 overexpression on monocytes/macrophages and FLS in RA patients may be responsible for the enhanced MMP secretion and activation and for the invasiveness of synoviocytes. These findings suggest that CD147 may be one of the important factors in progressive joint destruction of RA and that CD147 may be a potential therapeutic target in RA treatment.",2006 Feb 8,"['Zhu, Ping', 'Lu, Ning', 'Shi, Zhan-guo', 'Zhou, Jun', 'Wu, Zhen-biao', 'Yang, Yong', 'Ding, Jin', 'Chen, Zhi-nan']",Arthritis Res Ther,,,True
2bd6e33d92632dfcba4056a2d7355ced5b7ab1fd,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,True
76481505399740984fe9bf11fdfec984fbf11e32,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,True
f6686ac18c05ec72b33fbed5485fc922531d2529,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,True
84ad793db6fd5878929791f4a2f50943881206f1,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,True
6fe7dbbe77090cf3a1ac5ce68b0aca877c08dd71,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,True
f529616d665d71bd3aeb449334a8dc0e345e9e49,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,False
8a673053b68dec16bccca1928f8f584351633eaa,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,False
f4f5ea10677874343c578304f0c7d9d0f9a0fae1,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,False
0f8893808429b542f91b20eb3b34581fe65296bc,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,False
104a23fead757f1b8272ae0813db98b413375ae0,PMC,Streptococcus pneumoniae induced c-Jun-N-terminal kinase- and AP-1 -dependent IL-8 release by lung epithelial BEAS-2B cells,http://dx.doi.org/10.1186/1465-9921-7-98,PMC1533820,16834785,CC BY,"BACKGROUND: Although pneumococcal pneumonia is one of the most common causes of death due to infectious diseases, little is known about pneumococci-lung cell interaction. Herein we tested the hypothesis that pneumococci activated pulmonary epithelial cell cytokine release by c-Jun-NH(2)-terminal kinase (JNK) METHODS: Human bronchial epithelial cells (BEAS-2B) or epithelial HEK293 cells were infected with S. pneumoniae R6x and cytokine induction was measured by RT-PCR, ELISA and Bioplex assay. JNK-phosphorylation was detected by Western blot and nuclear signaling was assessed by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). JNK was modulated by the small molecule inhibitor SP600125 and AP1 by transfection of a dominant negative mutant. RESULTS: S. pneumoniae induced the release of distinct CC and CXC, as well as Th1 and Th2 cytokines and growth factors by human lung epithelial cell line BEAS-2B. Furthermore, pneumococci infection resulted in JNK phosphorylation in BEAS-2B cells. Inhibition of JNK by small molecule inhibitor SP600125 reduced pneumococci-induced IL-8 mRNA expression and release of IL-8 and IL-6. One regulator of the il8 promoter is JNK-phosphorylated activator protein 1 (AP-1). We showed that S. pneumoniae time-dependently induced DNA binding of AP-1 and its phosphorylated subunit c-Jun with a maximum at 3 to 5 h after infection. Recruitment of Ser(63/73)-phosphorylated c-Jun and RNA polymerase II to the endogenous il8 promoter was found 2 h after S. pneumoniae infection by chromatin immunoprecipitation. AP-1 repressor A-Fos reduced IL-8 release by TLR2-overexpressing HEK293 cells induced by pneumococci but not by TNFα. Antisense-constructs targeting the AP-1 subunits Fra1 and Fra2 had no inhibitory effect on pneumococci-induced IL-8 release. CONCLUSION: S. pneumoniae-induced IL-8 expression by human epithelial BEAS-2B cells depended on activation of JNK and recruitment of phosphorylated c-Jun to the il8 promoter.",2006 Jul 12,"['Schmeck, Bernd', 'Moog, Kerstin', 'Zahlten, Janine', 'van Laak, Vincent', ""N'Guessan, Philippe Dje"", 'Opitz, Bastian', 'Rosseau, Simone', 'Suttorp, Norbert', 'Hippenstiel, Stefan']",Respir Res,,,True
adeb15fc330fe6710ad1c979d0a33035b52f3ba0,PMC,Lung epithelium as a sentinel and effector system in pneumonia – molecular mechanisms of pathogen recognition and signal transduction,http://dx.doi.org/10.1186/1465-9921-7-97,PMC1533821,16827942,CC BY,"Pneumonia, a common disease caused by a great diversity of infectious agents is responsible for enormous morbidity and mortality worldwide. The bronchial and lung epithelium comprises a large surface between host and environment and is attacked as a primary target during lung infection. Besides acting as a mechanical barrier, recent evidence suggests that the lung epithelium functions as an important sentinel system against pathogens. Equipped with transmembranous and cytosolic pathogen-sensing pattern recognition receptors the epithelium detects invading pathogens. A complex signalling results in epithelial cell activation, which essentially participates in initiation and orchestration of the subsequent innate and adaptive immune response. In this review we summarize recent progress in research focussing on molecular mechanisms of pathogen detection, host cell signal transduction, and subsequent activation of lung epithelial cells by pathogens and their virulence factors and point to open questions. The analysis of lung epithelial function in the host response in pneumonia may pave the way to the development of innovative highly needed therapeutics in pneumonia in addition to antibiotics.",2006 Jul 8,"['Hippenstiel, Stefan', 'Opitz, Bastian', 'Schmeck, Bernd', 'Suttorp, Norbert']",Respir Res,,,True
ea23fbae1cee451e0beca6f5b2f6684519f63a67,PMC,Genome Annotation Transfer Utility (GATU): rapid annotation of viral genomes using a closely related reference genome,http://dx.doi.org/10.1186/1471-2164-7-150,PMC1534038,16772042,CC BY,"BACKGROUND: Since DNA sequencing has become easier and cheaper, an increasing number of closely related viral genomes have been sequenced. However, many of these have been deposited in GenBank without annotations, severely limiting their value to researchers. While maintaining comprehensive genomic databases for a set of virus families at the Viral Bioinformatics Resource Center and Viral Bioinformatics – Canada , we found that researchers were unnecessarily spending time annotating viral genomes that were close relatives of already annotated viruses. We have therefore designed and implemented a novel tool, Genome Annotation Transfer Utility (GATU), to transfer annotations from a previously annotated reference genome to a new target genome, thereby greatly reducing this laborious task. RESULTS: GATU transfers annotations from a reference genome to a closely related target genome, while still giving the user final control over which annotations should be included. GATU also detects open reading frames present in the target but not the reference genome and provides the user with a variety of bioinformatics tools to quickly determine if these ORFs should also be included in the annotation. After this process is complete, GATU saves the newly annotated genome as a GenBank, EMBL or XML-format file. The software is coded in Java and runs on a variety of computer platforms. Its user-friendly Graphical User Interface is specifically designed for users trained in the biological sciences. CONCLUSION: GATU greatly simplifies the initial stages of genome annotation by using a closely related genome as a reference. It is not intended to be a gene prediction tool or a ""complete"" annotation system, but we have found that it significantly reduces the time required for annotation of genes and mature peptides as well as helping to standardize gene names between related organisms by transferring reference genome annotations to the target genome. The program is freely available under the General Public License and can be accessed along with documentation and tutorial from .",2006 Jun 13,"['Tcherepanov, Vasily', 'Ehlers, Angelika', 'Upton, Chris']",BMC Genomics,,,True
6cfcbd2a102a3666d0d168f9bdaba0b2107fc8bd,PMC,Reliability of case definitions for public health surveillance assessed by Round-Robin test methodology,http://dx.doi.org/10.1186/1471-2458-6-129,PMC1538585,16686946,CC BY,"BACKGROUND: Case definitions have been recognized to be important elements of public health surveillance systems. They are to assure comparability and consistency of surveillance data and have crucial impact on the sensitivity and the positive predictive value of a surveillance system. The reliability of case definitions has rarely been investigated systematically. METHODS: We conducted a Round-Robin test by asking all 425 local health departments (LHD) and the 16 state health departments (SHD) in Germany to classify a selection of 68 case examples using case definitions. By multivariate analysis we investigated factors linked to classification agreement with a gold standard, which was defined by an expert panel. RESULTS: A total of 7870 classifications were done by 396 LHD (93%) and all SHD. Reporting sensitivity was 90.0%, positive predictive value 76.6%. Polio case examples had the lowest reporting precision, salmonellosis case examples the highest (OR = 0.008; CI: 0.005–0.013). Case definitions with a check-list format of clinical criteria resulted in higher reporting precision than case definitions with a narrative description (OR = 3.08; CI: 2.47–3.83). Reporting precision was higher among SHD compared to LHD (OR = 1.52; CI: 1.14–2.02). CONCLUSION: Our findings led to a systematic revision of the German case definitions and build the basis for general recommendations for the creation of case definitions. These include, among others, that testable yes/no criteria in a check-list format is likely to improve reliability, and that software used for data transmission should be designed in strict accordance with the case definitions. The findings of this study are largely applicable to case definitions in many other countries or international networks as they share the same structural and editorial characteristics of the case definitions evaluated in this study before their revision.",2006 May 10,"['Krause, Gérard', 'Brodhun, Bonita', 'Altmann, Doris', 'Claus, Hermann', 'Benzler, Justus']",BMC Public Health,,,True
67727dc7bb076ef6ddeb55c754af98e672ee60e0,PMC,Live bacterial vaccines – a review and identification of potential hazards,http://dx.doi.org/10.1186/1475-2859-5-23,PMC1538998,16796731,CC BY,"The use of live bacteria to induce an immune response to itself or to a carried vaccine component is an attractive vaccine strategy. Advantages of live bacterial vaccines include their mimicry of a natural infection, intrinsic adjuvant properties and their possibility to be administered orally. Derivatives of pathogenic and non-pathogenic food related bacteria are currently being evaluated as live vaccines. However, pathogenic bacteria demands for attenuation to weaken its virulence. The use of bacteria as vaccine delivery vehicles implies construction of recombinant strains that contain the gene cassette encoding the antigen. With the increased knowledge of mucosal immunity and the availability of genetic tools for heterologous gene expression the concept of live vaccine vehicles gains renewed interest. However, administration of live bacterial vaccines poses some risks. In addition, vaccination using recombinant bacteria results in the release of live recombinant organisms into nature. This places these vaccines in the debate on application of genetically modified organisms. In this review we give an overview of live bacterial vaccines on the market and describe the development of new live vaccines with a focus on attenuated bacteria and food-related lactic acid bacteria. Furthermore, we outline the safety concerns and identify the hazards associated with live bacterial vaccines and try to give some suggestions of what to consider during their development.",2006 Jun 23,"['Detmer, Ann', 'Glenting, Jacob']",Microb Cell Fact,,,True
78326020e9f7cd75415a3a192729ccf0c0930281,PMC,Association of SARS susceptibility with single nucleic acid polymorphisms of OAS1 and MxA genes: a case-control study,http://dx.doi.org/10.1186/1471-2334-6-106,PMC1550407,16824203,CC BY,"BACKGROUND: Host genetic factors may play a role in susceptibility and resistance to SARS associated coronavirus (SARS-CoV) infection. The study was carried out to investigate the association between the genetic polymorphisms of 2',5'-oligoadenylate synthetase 1 (OAS1) gene as well as myxovirus resistance 1 (MxA) gene and susceptibility to SARS in Chinese Han population. METHODS: A hospital-based case-control study was conducted. A collective of 66 SARS cases and 64 close contact uninfected controls were enrolled in this study. End point real time polymerase chain reaction (PCR) and PCR-based Restriction Fragment Length Polymorphism (RFLP) analysis were used to detect the single nucleic polymorphisms (SNPs) in OAS1 and MxA genes. Information on other factors associated with SARS infection was collected using a pre-tested questionnaire. Univariate and multivariate logistic analyses were conducted. RESULTS: One polymorphism in the 3'-untranslated region (3'-UTR) of the OAS1 gene was associated with SARS infection. Compared to AA genotype, AG and GG genotypes were found associated with a protective effect on SARS infection with ORs (95% CI) of 0.42 (0.20~0.89) and 0.30 (0.09~0.97), respectively. Also, a GT genotype at position 88 in the MxA gene promoter was associated with increased susceptibility to SARS infection compared to a GG genotype (OR = 3.06, 95% CI: 1.25~7.50). The associations of AG genotype in OAS1 and GT genotype in MxA remained significant in multivariate analyses after adjusting for SARS protective measures (OR = 0.38, 95% CI: 0.14~0.98 and OR = 3.22, 95% CI: 1.13~9.18, respectively). CONCLUSION: SNPs in the OAS1 3'-UTR and MxA promoter region appear associated with host susceptibility to SARS in Chinese Han population.",2006 Jul 6,"['He, Jing', 'Feng, Dan', 'de Vlas, Sake J', 'Wang, Hongwei', 'Fontanet, Arnaud', 'Zhang, Panhe', 'Plancoulaine, Sabine', 'Tang, Fang', 'Zhan, Lin', 'Yang, Hong', 'Wang, Tianbao', 'Richardus, Jan H', 'Habbema, J Dik F', 'Cao, Wuchun']",BMC Infect Dis,,,True
976dd497031581e697cbf2d98042f7c184e9fb40,PMC,Frequent detection of bocavirus DNA in German children with respiratory tract infections,http://dx.doi.org/10.1186/1471-2334-6-109,PMC1550408,16834781,CC BY,"BACKGROUND: In a substantial proportion of respiratory tract diseases of suspected infectious origin, the etiology is unknown. Some of these cases may be caused by the recently described human bocavirus (hBoV). The aim of this study was to investigate the frequency and the potential clinical relevance of hBoV in pediatric patients. METHODS: We tested 835 nasopharyngeal aspirates (NPA) obtained between 2002 and 2005 from pediatric in-patients with acute respiratory tract diseases at the University of Würzburg, Germany, for the presence of hBoV DNA. The specificity of positive PCR reactions was confirmed by sequencing. RESULTS: HBoV DNA was found in 87 (10.3 %) of the NPAs. The median age of the infants and children with hBoV infection was 1.8 years (mean age 2.0 years; range 18 days – 8 years). Infections with hBoV were found year-round, though most occurred in the winter months. Coinfections were found in 34 (39.1 %) of the hBoV positive samples. RSV, influenza A, and adenoviruses were most frequently detected as coinfecting agents. Sequence determination of the PCR products in the NP-1 region revealed high identity (99 %) between the nucleotide sequences obtained in different years and in comparison to the Swedish viruses ST1 and ST2. An association of hBoV with a distinct respiratory tract manifestation was not apparent. CONCLUSION: HBoV is frequently found in NPAs of hospitalized infants and children with acute respiratory tract diseases. Proving the clinical relevance of hBoV is challenging, because application of some of Koch's revised postulates is not possible. Because of the high rate of coinfections with hBoV and other respiratory tract pathogens, an association between hBoV and respiratory tract diseases remains unproven.",2006 Jul 11,"['Weissbrich, Benedikt', 'Neske, Florian', 'Schubert, Jörg', 'Tollmann, Franz', 'Blath, Katharina', 'Blessing, Kerstin', 'Kreth, Hans Wolfgang']",BMC Infect Dis,,,True
31d83e6ac0ab75190caaa5d5bcbb2fb745fc98cc,PMC,What Internet Services Would Patients Like From Hospitals During an Epidemic? Lessons From the SARS Outbreak in Toronto,http://dx.doi.org/10.2196/jmir.7.4.e46,PMC1550678,16236698,CC BY,"BACKGROUND: International health organizations and officials are bracing for a pandemic. Although the 2003 severe acute respiratory syndrome (SARS) outbreak in Toronto did not reach such a level, it created a unique opportunity to identify the optimal use of the Internet to promote communication with the public and to preserve health services during an epidemic. OBJECTIVE: The aim of the study was to explore patients’ attitudes regarding the health services that might be provided through the Internet to supplement those traditionally available in the event of a future mass emergency situation. METHODS: We conducted “mask-to-mask” surveys of patients at three major teaching hospitals in Toronto during the second outbreak of SARS. Patients were surveyed at the hospital entrances and selected clinics. Descriptive statistics and logistic regression models were used for the analysis. RESULTS: In total, 1019 of 1130 patients responded to the survey (90% overall response rate). With respect to Internet use, 70% (711/1019) used the Internet by themselves and 57% (578/1019) with the help of a friend or family member. Of the Internet users, 68% (485/711) had already searched the World Wide Web for health information, and 75% (533/711) were interested in communicating with health professionals using the Internet as part of their ongoing care. Internet users expressed interest in using the Web for the following reasons: to learn about their health condition through patient education materials (84%), to obtain information about the status of their clinic appointments (83%), to send feedback to the hospital about how to improve its services (77%), to access screening tools to help determine if they were potentially affected by the infectious agent responsible for the outbreak (77%), to renew prescriptions (75%), to consult with their health professional about nonurgent matters (75%), and to access laboratory test results (75%). Regression results showed that younger age, higher education, and English as a first language were predictors of patients’ interest in using Internet services in the event of an epidemic. CONCLUSION: Most patients are willing and able to use the Internet as a means to maintain communication with the hospital during an outbreak of an infectious disease such as SARS. Hospitals should explore new ways to interact with the public, to provide relevant health information, and to ensure continuity of care when they are forced to restrict their services.",2005 Aug 3,"['Rizo, Carlos A', 'Lupea, Doina', 'Baybourdy, Homayoun', 'Anderson, Matthew', 'Closson, Tom', 'Jadad, Alejandro R']",J Med Internet Res,,,False
bcaf2f13566d01650664af7ef4f8a3a9aa6b2b71,PMC,What Internet Services Would Patients Like From Hospitals During an Epidemic? Lessons From the SARS Outbreak in Toronto,http://dx.doi.org/10.2196/jmir.7.4.e46,PMC1550678,16236698,CC BY,"BACKGROUND: International health organizations and officials are bracing for a pandemic. Although the 2003 severe acute respiratory syndrome (SARS) outbreak in Toronto did not reach such a level, it created a unique opportunity to identify the optimal use of the Internet to promote communication with the public and to preserve health services during an epidemic. OBJECTIVE: The aim of the study was to explore patients’ attitudes regarding the health services that might be provided through the Internet to supplement those traditionally available in the event of a future mass emergency situation. METHODS: We conducted “mask-to-mask” surveys of patients at three major teaching hospitals in Toronto during the second outbreak of SARS. Patients were surveyed at the hospital entrances and selected clinics. Descriptive statistics and logistic regression models were used for the analysis. RESULTS: In total, 1019 of 1130 patients responded to the survey (90% overall response rate). With respect to Internet use, 70% (711/1019) used the Internet by themselves and 57% (578/1019) with the help of a friend or family member. Of the Internet users, 68% (485/711) had already searched the World Wide Web for health information, and 75% (533/711) were interested in communicating with health professionals using the Internet as part of their ongoing care. Internet users expressed interest in using the Web for the following reasons: to learn about their health condition through patient education materials (84%), to obtain information about the status of their clinic appointments (83%), to send feedback to the hospital about how to improve its services (77%), to access screening tools to help determine if they were potentially affected by the infectious agent responsible for the outbreak (77%), to renew prescriptions (75%), to consult with their health professional about nonurgent matters (75%), and to access laboratory test results (75%). Regression results showed that younger age, higher education, and English as a first language were predictors of patients’ interest in using Internet services in the event of an epidemic. CONCLUSION: Most patients are willing and able to use the Internet as a means to maintain communication with the hospital during an outbreak of an infectious disease such as SARS. Hospitals should explore new ways to interact with the public, to provide relevant health information, and to ensure continuity of care when they are forced to restrict their services.",2005 Aug 3,"['Rizo, Carlos A', 'Lupea, Doina', 'Baybourdy, Homayoun', 'Anderson, Matthew', 'Closson, Tom', 'Jadad, Alejandro R']",J Med Internet Res,,,False
aecd12a815bf5fd6486b92bc8fb631d00fef541f,PMC,Using simulation for training and to change protocol during the outbreak of severe acute respiratory syndrome,http://dx.doi.org/10.1186/cc3916,PMC1550819,16356209,CC BY,"INTRODUCTION: During the 2003 severe acute respiratory syndrome (SARS) crisis, we proposed and tested a new protocol for cardiac arrest in a patient with SARS. The protocol was rapidly and effectively instituted by teamwork training using high-fidelity simulation. METHODS: Phase 1 was a curriculum design of a SARS-specific cardiac arrest protocol in three steps: planning the new protocol, repeated simulations of this protocol in a classroom, and a subsequent simulation of a cardiac arrest on a hospital ward. Phase 2 was the training of 275 healthcare workers (HCWs) using the new protocol. Training involved a seminar, practice in wearing the mandatory personal protection system (PPS), and cardiac arrest simulations with subsequent debriefing. RESULTS: Simulation provided insights that had not been considered in earlier phases of development. For example, a single person can don a PPS worn for the SARS patient in 1 1/2 minutes. However, when multiple members of a cardiac arrest team were dressing simultaneously, the time to don the PPS increased to between 3 1/2 and 5 1/2 minutes. Errors in infection control as well as in medical management of advanced cardiac life support (ACLS) were corrected. CONCLUSION: During the SARS crisis, real-time use of a high-fidelity simulator allowed the training of 275 HCWs in 2 weeks, with debriefing and error management. HCWs were required to manage the SARS cardiac arrest wearing unfamiliar equipment and following a modified ACLS protocol. The insight gained from this experience will be valuable for future infectious disease challenges in critical care.",2006 Nov 24,"['Abrahamson, Simon D', 'Canzian, Sonya', 'Brunet, Fabrice']",Crit Care,,,True
5afe948e33645324e3fb0fe4e4d27b1bba317364,PMC,Diagnostic value of real-time polymerase chain reaction to detect viruses in young children admitted to the paediatric intensive care unit with lower respiratory tract infection,http://dx.doi.org/10.1186/cc4895,PMC1550925,16611370,CC BY,"INTRODUCTION: The aetiology of lower respiratory tract infections in young children admitted to the paediatric intensive care unit (PICU) is often difficult to establish. However, most infections are believed to be caused by respiratory viruses. A diagnostic study was performed to compare conventional viral tests with the recently developed real-time PCR technique. METHOD: Samples from children aged under 5 years presenting to a tertiary PICU suspected of having a lower respiratory tract infection were tested using conventional methods (viral culture and immunofluorescence) and real-time PCR during the winter season from December 2004 to May 2005. Conventional methods were used to check for respiratory syncytial virus, influenzavirus, parainfluenzavirus 1–3, rhinoviruses and adenoviruses. Real-time PCR was used to test for respiratory syncytial virus, influenzavirus, parainfluenzavirus 1–4, rhinoviruses, adenoviruses, human coronaviruses OC43, NL63 and 229E, human metapneumovirus, Mycoplasma pneumoniae and Chlamydia pneumoniae. RESULTS: A total of 23 patients were included, of whom 11 (48%) were positive for a respiratory virus by conventional methods. Real-time PCR confirmed all of these positive results. In addition, real-time PCR identified 22 more viruses in 11 patients, yielding a total of 22 (96%) patients with a positive sample. More than one virus was detected in eight (35%) children. CONCLUSION: Real-time PCR for respiratory viruses was found to be a sensitive and reliable method in PICU patients with lower respiratory tract infection, increasing the diagnostic yield twofold compared to conventional methods.",2006 Apr 12,"['van de Pol, Alma C', 'Wolfs, Tom FW', 'Jansen, Nicolaas JG', 'van Loon, Anton M', 'Rossen, John WA']",Crit Care,,,True
4c84dbfd01f7b2009ebed54376da8afcbcf1ec64,PMC,Model-Based Design of Growth-Attenuated Viruses,http://dx.doi.org/10.1371/journal.pcbi.0020116,PMC1557587,16948530,CC BY,"Live-virus vaccines activate both humoral and cell-mediated immunity, require only a single boosting, and generally provide longer immune protection than killed or subunit vaccines. However, growth of live-virus vaccines must be attenuated to minimize their potential pathogenic effects, and mechanisms of attenuation by conventional serial-transfer viral adaptation are not well-understood. New methods of attenuation based on rational engineering of viral genomes may offer a potentially greater control if one can link defined genetic modifications to changes in virus growth. To begin to establish such links between genotype and growth phenotype, we developed a computer model for the intracellular growth of vesicular stomatitis virus (VSV), a well-studied, nonsegmented, negative-stranded RNA virus. Our model incorporated established regulatory mechanisms of VSV while integrating key wild-type infection steps: hijacking of host resources, transcription, translation, and replication, followed by assembly and release of progeny VSV particles. Generalization of the wild-type model to allow for genome rearrangements matched the experimentally observed attenuation ranking for recombinant VSV strains that altered the genome position of their nucleocapsid gene. Finally, our simulations captured previously reported experimental results showing how altering the positions of other VSV genes has the potential to attenuate the VSV growth while overexpressing the immunogenic VSV surface glycoprotein. Such models will facilitate the engineering of new live-virus vaccines by linking genomic manipulations to controlled changes in virus gene-expression and growth.",2006 Sep 1,"['Lim, Kwang-il', 'Lang, Tobias', 'Lam, Vy', 'Yin, John']",PLoS Comput Biol,,,True
6c6ac6629c8a603c01953ae37469014700102ed8,PMC,Hospice utilization during the SARS outbreak in Taiwan,http://dx.doi.org/10.1186/1472-6963-6-94,PMC1559606,16889656,CC BY,"BACKGROUND: The severe acute respiratory syndrome (SARS) epidemic threw the world into turmoil during the first half of 2003. Many subsequent papers have addressed its impact on health service utilization, but few have considered palliative (hospice) care. The aim of the present study was to describe changes in hospice inpatient utilization during and after the SARS epidemic in 2003 in Taiwan. METHODS: The data sources were the complete datasets of inpatient admissions during 2002 and 2003 from the National Health Insurance Research Database. Before-and-after comparisons of daily and monthly utilizations were made. Hospice analyses were limited to those wards that offered inpatient services throughout these two years. The comparisons were extended to total hospital bed utilization and to patients who were still admitted to hospice wards during the peak period of the SARS epidemic. RESULTS: Only 15 hospice wards operated throughout the whole of 2002 and 2003. In 2003, hospice utilization began to decrease in the middle of April, reached a minimum on 25 May, and gradually recovered to the level of the previous November. Hospices showed a more marked reduction in utilization than all hospital beds (e.g. -52.5% vs. -19.9% in May 2003) and a slower recovery with a three-month lag. In total, 566 patients were admitted to hospice wards in May/June 2003, in contrast to 818 in May/June 2002. Gender, age and diagnosis distributions did not differ. CONCLUSION: Hospice inpatient utilization in Taiwan was indeed more sensitive to the emerging epidemic than general inpatient utilization. A well-balanced network with seamless continuity of care should be ensured.",2006 Aug 4,"['Chen, Tzeng-Ji', 'Lin, Ming-Hwai', 'Chou, Li-Fang', 'Hwang, Shinn-Jang']",BMC Health Serv Res,,,True
5faef288fa2cd3e02a6d12b9e09912decde1032c,PMC,"Ethnoveterinary medicines used for horses in Trinidad and in British Columbia, Canada",http://dx.doi.org/10.1186/1746-4269-2-31,PMC1559680,16893454,CC BY,"This paper investigates the commonalities in ethnoveterinary medicine used for horses between Trinidad (West Indies) and British Columbia (Canada). These research areas are part of a common market in pharmaceuticals and are both involved in the North American racing circuit. There has been very little research conducted on medicinal plants used for horses although their use is widespread. The data on ethnoveterinary medicines used for horses was obtained through key informant interviews with horse owners, trainers, breeders, jockeys, grooms and animal care specialists in two research areas: Trinidad and British Columbia (BC). A participatory validation workshop was held in BC. An extensive literature review and botanical identification of the plants was also done. In all, 20 plants were found to be used in treating racehorses in Trinidad and 97 in BC. Of these the most-evidently effective plants 19 of the plants used in Trinidad and 66 of those used in BC are described and evaluated in this paper. Aloe vera, Curcuma longa and Ricinus communis are used in both research areas. More research is needed in Trinidad to identify plants that respondents claimed were used in the past. Far more studies have been conducted on the temperate and Chinese medicinal plants used in BC and therefore these ethnoveterinary remedies reflect stronger evidence of efficacy.",2006 Aug 7,"['Lans, Cheryl', 'Turner, Nancy', 'Brauer, Gerhard', 'Lourenco, Grant', 'Georges, Karla']",J Ethnobiol Ethnomed,,,True
275d7a25357ea46699072167d4ca109108132068,PMC,Surveillance recommendations based on an exploratory analysis of respiratory syncytial virus reports derived from the European Influenza Surveillance System,http://dx.doi.org/10.1186/1471-2334-6-128,PMC1560143,16899110,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is an important pathogen that can cause severe illness in infants and young children. In this study, we assessed whether data on RSV collected by the European Influenza Surveillance Scheme (EISS) could be used to build an RSV surveillance system in Europe. METHODS: Influenza and RSV data for the 2002–2003 winter season were analysed for England, France, the Netherlands and Scotland. Data from sentinel physician networks and other sources, mainly hospitals, were collected. Respiratory specimens were tested for influenza and RSV mainly by virus culture and polymerase chain reaction amplification. RESULTS: Data on RSV were entered timely into the EISS database. RSV contributed noticeably to influenza-like illness: in England sentinel RSV detections were common in all age groups, but particularly in young children with 20 (40.8%) of the total number of sentinel swabs testing positive for RSV. Scotland and France also reported the highest percentages of RSV detections in the 0–4 year age group, respectively 10.3% (N = 29) and 12.2% (N = 426). In the Netherlands, RSV was detected in one person aged over 65 years. CONCLUSION: We recommend that respiratory specimens collected in influenza surveillance are also tested systematically for RSV and emphasize the use of both community derived data and data from hospitals for RSV surveillance. RSV data from the EISS have been entered in a timely manner and we consider that the EISS model can be used to develop an RSV surveillance system equivalent to the influenza surveillance in Europe.",2006 Aug 9,"['Meerhoff, Tamara J', 'Fleming, Douglas', 'Smith, Ann', 'Mosnier, Anne', 'van Gageldonk-Lafeber, Arianne B', 'Paget, W John', None]",BMC Infect Dis,,,True
8bcd86c97a06dbdff096f6cb164f9dab35f879f9,PMC,"Factors associated with nosocomial SARS-CoV transmission among healthcare workers in Hanoi, Vietnam, 2003",http://dx.doi.org/10.1186/1471-2458-6-207,PMC1562405,16907978,CC BY,"BACKGROUND: In March of 2003, an outbreak of Severe Acute Respiratory Syndrome (SARS) occurred in Northern Vietnam. This outbreak began when a traveler arriving from Hong Kong sought medical care at a small hospital (Hospital A) in Hanoi, initiating a serious and substantial transmission event within the hospital, and subsequent limited spread within the community. METHODS: We surveyed Hospital A personnel for exposure to the index patient and for symptoms of disease during the outbreak. Additionally, serum specimens were collected and assayed for antibody to SARS-associated coronavirus (SARS-CoV) antibody and job-specific attack rates were calculated. A nested case-control analysis was performed to assess risk factors for acquiring SARS-CoV infection. RESULTS: One hundred and fifty-three of 193 (79.3%) clinical and non-clinical staff consented to participate. Excluding job categories with <3 workers, the highest SARS attack rates occurred among nurses who worked in the outpatient and inpatient general wards (57.1, 47.4%, respectively). Nurses assigned to the operating room/intensive care unit, experienced the lowest attack rates (7.1%) among all clinical staff. Serologic evidence of SARS-CoV infection was detected in 4 individuals, including 2 non-clinical workers, who had not previously been identified as SARS cases; none reported having had fever or cough. Entering the index patient's room and having seen (viewed) the patient were the behaviors associated with highest risk for infection by univariate analysis (odds ratios 20.0, 14.0; 95% confidence intervals 4.1–97.1, 3.6–55.3, respectively). CONCLUSION: This study highlights job categories and activities associated with increased risk for SARS-CoV infection and demonstrates that a broad diversity of hospital workers may be vulnerable during an outbreak. These findings may help guide recommendations for the protection of vulnerable occupational groups and may have implications for other respiratory infections such as influenza.",2006 Aug 14,"['Reynolds, Mary G', 'Anh, Bach Huy', 'Thu, Vu Hoang', 'Montgomery, Joel M', 'Bausch, Daniel G', 'Shah, J Jina', 'Maloney, Susan', 'Leitmeyer, Katrin C', 'Huy, Vu Quang', 'Horby, Peter', 'Plant, Aileen Y', 'Uyeki, Timothy M']",BMC Public Health,,,True
d665907080d2eae92859eab542dce90a57f11efb,PMC,Mixing patterns and the spread of close-contact infectious diseases,http://dx.doi.org/10.1186/1742-7622-3-10,PMC1562421,16907980,CC BY,"Surprisingly little is known regarding the human mixing patterns relevant to the spread of close-contact infections, such as measles, influenza and meningococcal disease. This study aims to estimate the number of partnerships that individuals make, their stability and the degree to which mixing is assortative with respect to age. We defined four levels of putative at-risk events from casual (physical contact without conversation) to intimate (contact of a sexual nature), and asked university student volunteers to record details on those they contacted at these levels on three separate days. We found that intimate contacts are stable over short time periods whereas there was no evidence of repeat casual contacts with the same individuals. The contacts were increasingly assortative as intimacy increased. Such information will aid the development and parameterisation of models of close contact diseases, and may have direct use in outbreak investigations.",2006 Aug 14,"['Edmunds, WJ', 'Kafatos, G', 'Wallinga, J', 'Mossong, JR']",Emerg Themes Epidemiol,,,True
3ebb8d173e6297001673ec3ce3bb14e5c1cb9715,PMC,Caveolin-1 and -2 in airway epithelium: expression and in situ association as detected by FRET-CLSM,http://dx.doi.org/10.1186/1465-9921-7-108,PMC1563466,16904002,CC BY,"BACKGROUND: Caveolae are involved in diverse cellular functions such as signal transduction, cholesterol homeostasis, endo- and transcytosis, and also may serve as entry sites for microorganisms. Hence, their occurrence in epithelium of the airways might be expected but, nonetheless, has not yet been examined. METHODS: Western blotting, real-time quantitative PCR analysis of abraded tracheal epithelium and laser-assisted microdissection combined with subsequent mRNA analysis were used to examine the expression of cav-1 and cav-2, two major caveolar coat proteins, in rat tracheal epithelium. Fluorescence immunohistochemistry was performed to locate caveolae and cav-1 and -2 in the airway epithelium of rats, mice and humans. Electron-microscopic analysis was used for the identification of caveolae. CLSM-FRET analysis determined the interaction of cav-1α and cav-2 in situ. RESULTS: Western blotting and laser-assisted microdissection identified protein and transcripts, respectively, of cav-1 and cav-2 in airway epithelium. Real-time quantitative RT-PCR analysis of abraded tracheal epithelium revealed a higher expression of cav-2 than of cav-1. Immunoreactivities for cav-1 and for cav-2 were co-localized in the cell membrane of the basal cells and basolaterally in the ciliated epithelial cells of large airways of rat and human. However, no labeling for cav-1 or cav-2 was observed in the epithelial cells of small bronchi. Using conventional double-labeling indirect immunofluorescence combined with CLSM-FRET analysis, we detected an association of cav-1α and -2 in epithelial cells. The presence of caveolae was confirmed by electron microscopy. In contrast to human and rat, cav-1-immunoreactivity and caveolae were confined to basal cells in mice. Epithelial caveolae were absent in cav-1-deficient mice, implicating a requirement of this caveolar protein in epithelial caveolae formation. CONCLUSION: These results show that caveolae and caveolins are integral membrane components in basal and ciliated epithelial cells, indicating a crucial role in these cell types. In addition to their physiological role, they may be involved in airway infection.",2006 Aug 11,"['Krasteva, Gabriela', 'Pfeil, Uwe', 'Drab, Marek', 'Kummer, Wolfgang', 'König, Peter']",Respir Res,,,True
968aa40cb4dd0cab313ecc59ff2f85800cbc1b8b,PMC,Genome-wide gene expression profiling of human mast cells stimulated by IgE or FcεRI-aggregation reveals a complex network of genes involved in inflammatory responses,http://dx.doi.org/10.1186/1471-2164-7-210,PMC1564015,16911805,CC BY,"BACKGROUND: Mast cells are well established effectors of IgE-triggered allergic reactions and immune responses to parasitic infections. Recent studies indicate that mast cells may play roles in adaptive and innate immunity, suggesting an innovative view of the regulation of immune responses. Here, we profiled the transcriptome of human mast cells sensitized with IgE alone, or stimulated by FcεRI aggregation. RESULTS: Our data show that among 8,793 genes examined, 559 genes are differentially regulated in stimulated mast cells when compared with resting/unstimulated mast cells. The major functional categories of upregulated genes include cytokines, chemokines, and other genes involved in innate and adaptive immune-responses. We observed the increased expression of over 63 gene-transcripts following IgE-sensitization alone. Our data was validated using Real-Time-PCR; ELISA and western blot. We confirmed that IgE alone does not trigger mast cell-immediate responses, such as calcium signals, degranulation or protein-phosphorylation. CONCLUSION: This report represents a substantial advance in our understanding of the genome wide effects triggered by ""passive sensitization"" or active stimulation of human mast cells, supporting mast cells' potential involvement in a wide range of inflammatory responses.",2006 Aug 16,"['Jayapal, Manikandan', 'Tay, Hwee Kee', 'Reghunathan, Renji', 'Zhi, Liang', 'Chow, Kah Kiong', 'Rauff, Mary', 'Melendez, Alirio J']",BMC Genomics,,,True
2884fdee6db20fa38c7ad56008b0ff4b84eeb41d,PMC,How long do nosocomial pathogens persist on inanimate surfaces? A systematic review,http://dx.doi.org/10.1186/1471-2334-6-130,PMC1564025,16914034,CC BY,"BACKGROUND: Inanimate surfaces have often been described as the source for outbreaks of nosocomial infections. The aim of this review is to summarize data on the persistence of different nosocomial pathogens on inanimate surfaces. METHODS: The literature was systematically reviewed in MedLine without language restrictions. In addition, cited articles in a report were assessed and standard textbooks on the topic were reviewed. All reports with experimental evidence on the duration of persistence of a nosocomial pathogen on any type of surface were included. RESULTS: Most gram-positive bacteria, such as Enterococcus spp. (including VRE), Staphylococcus aureus (including MRSA), or Streptococcus pyogenes, survive for months on dry surfaces. Many gram-negative species, such as Acinetobacter spp., Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Serratia marcescens, or Shigella spp., can also survive for months. A few others, such as Bordetella pertussis, Haemophilus influenzae, Proteus vulgaris, or Vibrio cholerae, however, persist only for days. Mycobacteria, including Mycobacterium tuberculosis, and spore-forming bacteria, including Clostridium difficile, can also survive for months on surfaces. Candida albicans as the most important nosocomial fungal pathogen can survive up to 4 months on surfaces. Persistence of other yeasts, such as Torulopsis glabrata, was described to be similar (5 months) or shorter (Candida parapsilosis, 14 days). Most viruses from the respiratory tract, such as corona, coxsackie, influenza, SARS or rhino virus, can persist on surfaces for a few days. Viruses from the gastrointestinal tract, such as astrovirus, HAV, polio- or rota virus, persist for approximately 2 months. Blood-borne viruses, such as HBV or HIV, can persist for more than one week. Herpes viruses, such as CMV or HSV type 1 and 2, have been shown to persist from only a few hours up to 7 days. CONCLUSION: The most common nosocomial pathogens may well survive or persist on surfaces for months and can thereby be a continuous source of transmission if no regular preventive surface disinfection is performed.",2006 Aug 16,"['Kramer, Axel', 'Schwebke, Ingeborg', 'Kampf, Günter']",BMC Infect Dis,,,True
5dc0b8b662824323881c3a1ae3a1bae2a821484d,PMC,SARS: Systematic Review of Treatment Effects,http://dx.doi.org/10.1371/journal.pmed.0030343,PMC1564166,16968120,CC0,"BACKGROUND: The SARS outbreak of 2002–2003 presented clinicians with a new, life-threatening disease for which they had no experience in treating and no research on the effectiveness of treatment options. The World Health Organization (WHO) expert panel on SARS treatment requested a systematic review and comprehensive summary of treatments used for SARS-infected patients in order to guide future treatment and identify priorities for research. METHODS AND FINDINGS: In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both in vitro studies and in SARS patients. We also searched for clinical trial evidence of treatment for acute respiratory distress syndrome. Sources of data were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to February 2005. Data from publications were extracted and evidence within studies was classified using predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies, and three acute respiratory distress syndrome studies met our inclusion criteria. Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26 studies were classified as inconclusive, and four showed possible harm. Seven studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four were classified as causing possible harm. CONCLUSIONS: Despite an extensive literature reporting on SARS treatments, it was not possible to determine whether treatments benefited patients during the SARS outbreak. Some may have been harmful. Clinical trials should be designed to validate a standard protocol for dosage and timing, and to accrue data in real time during future outbreaks to monitor specific adverse effects and help inform treatment.",2006 Sep 12,"['Stockman, Lauren J', 'Bellamy, Richard', 'Garner, Paul']",PLoS Med,,,True
7de21b4df4bb390e0fba8c0938ef6eeef9a4630e,PMC,A New Arthritis Therapy with Oxidative Burst Inducers,http://dx.doi.org/10.1371/journal.pmed.0030348,PMC1564167,16968121,CC BY,"BACKGROUND: Despite recent successes with biological agents as therapy for autoimmune inflammatory diseases such as rheumatoid arthritis (RA), many patients fail to respond adequately to these treatments, making a continued search for new therapies extremely important. Recently, the prevailing hypothesis that reactive oxygen species (ROS) promote inflammation was challenged when polymorphisms in Ncf1, that decrease oxidative burst, were shown to increase disease severity in mouse and rat arthritis models. Based on these findings we developed a new therapy for arthritis using oxidative burst-inducing substances. METHODS AND FINDINGS: Treatment of rats with phytol (3,7,11,15-tetramethyl-2-hexadecene-1-ol) increased oxidative burst in vivo and thereby corrected the effect of the genetic polymorphism in arthritis-prone Ncf1 (DA) rats. Importantly, phytol treatment also decreased the autoimmune response and ameliorated both the acute and chronic phases of arthritis. When compared to standard therapies for RA, anti-tumour necrosis factor-α and methotrexate, phytol showed equally good or better therapeutic properties. Finally, phytol mediated its effect within hours of administration and involved modulation of T cell activation, as injection prevented adoptive transfer of disease with arthritogenic T cells. CONCLUSIONS: Treatment of arthritis with ROS-promoting substances such as phytol targets a newly discovered pathway leading to autoimmune inflammatory disease and introduces a novel class of therapeutics for treatment of RA and possibly other chronic inflammatory diseases.",2006 Sep 12,"['Hultqvist, Malin', 'Olofsson, Peter', 'Gelderman, Kyra A', 'Holmberg, Jens', 'Holmdahl, Rikard']",PLoS Med,,,True
381f1d10b47e89d45a1008b53292c66c034b6960,PMC,Empirical Evidence for the Effect of Airline Travel on Inter-Regional Influenza Spread in the United States,http://dx.doi.org/10.1371/journal.pmed.0030401,PMC1564183,16968115,CC BY,"BACKGROUND: The influence of air travel on influenza spread has been the subject of numerous investigations using simulation, but very little empirical evidence has been provided. Understanding the role of airline travel in large-scale influenza spread is especially important given the mounting threat of an influenza pandemic. Several recent simulation studies have concluded that air travel restrictions may not have a significant impact on the course of a pandemic. Here, we assess, with empirical data, the role of airline volume on the yearly inter-regional spread of influenza in the United States. METHODS AND FINDINGS: We measured rate of inter-regional spread and timing of influenza in the United States for nine seasons, from 1996 to 2005 using weekly influenza and pneumonia mortality from the Centers for Disease Control and Prevention. Seasonality was characterized by band-pass filtering. We found that domestic airline travel volume in November (mostly surrounding the Thanksgiving holiday) predicts the rate of influenza spread (r (2) = 0.60; p = 0.014). We also found that international airline travel influences the timing of influenza mortality (r (2) = 0.59; p = 0.016). The flight ban in the US after the terrorist attack on September 11, 2001, and the subsequent depression of the air travel market, provided a natural experiment for the evaluation of flight restrictions; the decrease in air travel was associated with a delayed and prolonged influenza season. CONCLUSIONS: We provide the first empirical evidence for the role of airline travel in long-range dissemination of influenza. Our results suggest an important influence of international air travel on the timing of influenza introduction, as well as an influence of domestic air travel on the rate of inter-regional influenza spread in the US. Pandemic preparedness strategies should account for a possible benefit of airline travel restrictions on influenza spread.",2006 Oct 12,"['Brownstein, John S', 'Wolfe, Cecily J', 'Mandl, Kenneth D']",PLoS Med,,,True
cdffc1eadb85e776433b6850a2dd40a350874622,PMC,Natural products that reduce rotavirus infectivity identified by a cell-based moderate-throughput screening assay,http://dx.doi.org/10.1186/1743-422X-3-68,PMC1564392,16948846,CC BY,"BACKGROUND: There is widespread interest in the use of innate immune modulators as a defense strategy against infectious pathogens. Using rotavirus as a model system, we developed a cell-based, moderate-throughput screening (MTS) assay to identify compounds that reduce rotavirus infectivity in vitro, toward a long-term goal of discovering immunomodulatory agents that enhance innate responses to viral infection. RESULTS: A natural product library consisting of 280 compounds was screened in the assay and 15 compounds that significantly reduced infectivity without cytotoxicity were identified. Time course analysis of four compounds with previously characterized effects on inflammatory gene expression inhibited replication with pre-treatment times as minimal as 2 hours. Two of these four compounds, α-mangostin and 18-β-glycyrrhetinic acid, activated NFκB and induced IL-8 secretion. The assay is adaptable to other virus systems, and amenable to full automation and adaptation to a high-throughput format. CONCLUSION: Identification of several compounds with known effects on inflammatory and antiviral gene expression that confer resistance to rotavirus infection in vitro suggests the assay is an appropriate platform for discovery of compounds with potential to amplify innate antiviral responses.",2006 Sep 1,"['Shaneyfelt, Mark E', 'Burke, Anna D', 'Graff, Joel W', 'Jutila, Mark A', 'Hardy, Michele E']",Virol J,,,True
c6183dfbaabc06881c70097745b3e646479ac9a7,PMC,Climate Change and Human Health Impacts in the United States: An Update on the Results of the U.S. National Assessment,http://dx.doi.org/10.1289/ehp.8880,PMC1570072,16966082,CC0,"The health sector component of the first U.S. National Assessment, published in 2000, synthesized the anticipated health impacts of climate variability and change for five categories of health outcomes: impacts attributable to temperature, extreme weather events (e.g., storms and floods), air pollution, water- and food-borne diseases, and vector- and rodent-borne diseases. The Health Sector Assessment (HSA) concluded that climate variability and change are likely to increase morbidity and mortality risks for several climate-sensitive health outcomes, with the net impact uncertain. The objective of this study was to update the first HSA based on recent publications that address the potential impacts of climate variability and change in the United States for the five health outcome categories. The literature published since the first HSA supports the initial conclusions, with new data refining quantitative exposure–response relationships for several health end points, particularly for extreme heat events and air pollution. The United States continues to have a very high capacity to plan for and respond to climate change, although relatively little progress has been noted in the literature on implementing adaptive strategies and measures. Large knowledge gaps remain, resulting in a substantial need for additional research to improve our understanding of how weather and climate, both directly and indirectly, can influence human health. Filling these knowledge gaps will help better define the potential health impacts of climate change and identify specific public health adaptations to increase resilience.",2006 Sep 18,"['Ebi, Kristie L.', 'Mills, David M.', 'Smith, Joel B.', 'Grambsch, Anne']",Environ Health Perspect,,,True
7bb628111d2f63d10959355b1102887abeed0f44,PMC,Are Nonhuman Primates Good Models for SARS?,http://dx.doi.org/10.1371/journal.pmed.0030411,PMC1576335,17002511,CC BY,,2006 Sep 26,"Hogan, Robert J",PLoS Med,,,True
e1e11bdec2d27ec0b9675e684fc2653513a029bd,PMC,Authors' Response to Hogan,http://dx.doi.org/10.1371/journal.pmed.0030415,PMC1576339,,CC BY,,2006 Sep 26,"['Haagmans, Bart L', 'Osterhaus, Albert D. M. E']",PLoS Med,,,True
acc751e3f39515573231c168c3c530bfff91fee6,PMC,S1 gene sequence analysis of a nephropathogenic strain of avian infectious bronchitis virus in Egypt,http://dx.doi.org/10.1186/1743-422X-3-78,PMC1592083,16987422,CC BY,"BACKGROUND: Infectious bronchitis is highly contagious and constitutes one of the most common and difficult poultry diseases to control. IBV is endemic in probably all countries that raise chickens. It exists as dozens of serotypes/genotypes. Only a few amino acid differences in the S1 protein of vaccine and challenge strains of IBV may result in poor protection. Tropism of IBV includes the respiratory tract tissues, proventriculus and caecal tonsils of the alimentary tract, the oviduct and the kidney. RESULTS: Infectious bronchitis virus (IBV) strain closely related to Massachusetts (Mass) serotype was isolated from broiler chickens suffering from severe renal and respiratory distresses. The isolate was serologically identified by Dot-ELISA and further characterized by RT-PCR then genotyped using S1 gene sequence analysis. Alignment of the S1 sequence of the isolate with 16 IBV strains revealed high homology to isolates related to Mass serotype. Inoculation with the strain reproduced the disease in experimental 1-day-old chickens and resulted in 20% mortality, severe renal and moderate respiratory distresses. Marked histopathological changes in both kidney and trachea were observed in experimentally infected chickens. A protection study using the H120 live attenuated vaccine showed low protection rate in spite of high S1 sequence homology (97%). Protection based criteria were: virus re-isolation attempts from trachea, tracheal and renal histopathology as well as IBV antigens detection by immunofluorescent antibody technique in kidney sections. CONCLUSION: Periodical evaluation of cross-protective capabilities of IBV vaccine(s) versus recently recovered field isolates should be performed to ensure optimum control of IBV.",2006 Sep 20,"['Abdel-Moneim, Ahmed S', 'El-Kady, Magdy F', 'Ladman, Brian S', 'Gelb, Jack']",Virol J,,,True
9bf1241b4b35efdf7be808ce9bc8d44939f1e21e,PMC,Individual freedom versus collective responsibility: too many rights make a wrong?,http://dx.doi.org/10.1186/1742-7622-3-14,PMC1594563,17014728,CC BY,"Individuals might reasonably expect the freedom to make their own decisions regarding their health. However, what happens when an individual's wishes conflict with what is in that individual's best interests? How far should an individual's rights be restricted for his or her own benefit? Similarly, what limitations should be placed on an individual's behaviour when that person's wishes go against what is good for the population in general? Here we discuss the issues that can arise when the rights of individuals conflict with individual and population benefits in relation to infectious diseases.",2006 Oct 2,"['Looker, Katharine J', 'Hallett, Timothy B']",Emerg Themes Epidemiol,,,True
3e572863713d0fbe8cf60ea9991dd5c9993e6c7d,PMC,Validation of the Provincial Transfer Authorization Centre database: a comprehensive database containing records of all inter-facility patient transfers in the province of Ontario,http://dx.doi.org/10.1186/1472-6963-6-129,PMC1609112,17026763,CC BY,"BACKGROUND: The Provincial Transfer Authorization Centre (PTAC) was established as a part of the emergency response in Ontario, Canada to the Severe Acute Respiratory Syndrome (SARS) outbreak in 2003. Prior to 2003, data relating to inter-facility patient transfers were not collected in a systematic manner. Then, in an emergency setting, a comprehensive database with a complex data collection process was established. For the first time in Ontario, population-based data for patient movement between healthcare facilities for a population of twelve million are available. The PTAC database stores all patient transfer data in a large database. There are few population-based patient transfer databases and the PTAC database is believed to be the largest example to house this novel dataset. A patient transfer database has also never been validated. This paper presents the validation of the PTAC database. METHODS: A random sample of 100 patient inter-facility transfer records was compared to the corresponding institutional patient records from the sending healthcare facilities. Measures of agreement, including sensitivity, were calculated for the 12 common data variables. RESULTS: Of the 100 randomly selected patient transfer records, 95 (95%) of the corresponding institutional patient records were located. Data variables in the categories patient demographics, facility identification and timing of transfer and reason and urgency of transfer had strong agreement levels. The 10 most commonly used data variables had accuracy rates that ranged from 85.3% to 100% and error rates ranging from 0 to 12.6%. These same variables had sensitivity values ranging from 0.87 to 1.0. CONCLUSION: The very high level of agreement between institutional patient records and the PTAC data for fields compared in this study supports the validity of the PTAC database. For the first time, a population-based patient transfer database has been established. Although it was created during an emergency situation and data collection is dependent on front-line medical workers, the PTAC data has achieved a high level of validity, perhaps even higher than many purpose built databases created during non-emergency settings.",2006 Oct 6,"['Robinson, Victoria A', 'MacDonald, Russell D', 'Manuel, Doug', 'Goel, Vivek']",BMC Health Serv Res,,,True
9aa51dd5b5755afa670398027272f2e6b4f3d83b,PMC,Adaptive evolution of the spike gene of SARS coronavirus: changes in positively selected sites in different epidemic groups,http://dx.doi.org/10.1186/1471-2180-6-88,PMC1609170,17020602,CC BY,"BACKGROUND: It is believed that animal-to-human transmission of severe acute respiratory syndrome (SARS) coronavirus (CoV) is the cause of the SARS outbreak worldwide. The spike (S) protein is one of the best characterized proteins of SARS-CoV, which plays a key role in SARS-CoV overcoming species barrier and accomplishing interspecies transmission from animals to humans, suggesting that it may be the major target of selective pressure. However, the process of adaptive evolution of S protein and the exact positively selected sites associated with this process remain unknown. RESULTS: By investigating the adaptive evolution of S protein, we identified twelve amino acid sites (75, 239, 244, 311, 479, 609, 613, 743, 765, 778, 1148, and 1163) in the S protein under positive selective pressure. Based on phylogenetic tree and epidemiological investigation, SARS outbreak was divided into three epidemic groups: 02–04 interspecies, 03-early-mid, and 03-late epidemic groups in the present study. Positive selection was detected in the first two groups, which represent the course of SARS-CoV interspecies transmission and of viral adaptation to human host, respectively. In contrast, purifying selection was detected in 03-late group. These indicate that S protein experiences variable positive selective pressures before reaching stabilization. A total of 25 sites in 02–04 interspecies epidemic group and 16 sites in 03-early-mid epidemic group were identified under positive selection. The identified sites were different between these two groups except for site 239, which suggests that positively selected sites are changeable between groups. Moreover, it was showed that a larger proportion (24%) of positively selected sites was located in receptor-binding domain (RBD) than in heptad repeat (HR)1-HR2 region in 02–04 interspecies epidemic group (p = 0.0208), and a greater percentage (25%) of these sites occurred in HR1–HR2 region than in RBD in 03-early-mid epidemic group (p = 0.0721). These suggest that functionally different domains of S protein may not experience same positive selection in each epidemic group. In addition, three specific replacements (F360S, T487S and L665S) were only found between 03-human SARS-CoVs and strains from 02–04 interspecies epidemic group, which reveals that selective sweep may also force the evolution of S genes before the jump of SARS-CoVs into human hosts. Since certain residues at these positively selected sites are associated with receptor recognition and/or membrane fusion, they are likely to be the crucial residues for animal-to-human transmission of SARS-CoVs, and subsequent adaptation to human hosts. CONCLUSION: The variation of positive selective pressures and positively selected sites are likely to contribute to the adaptive evolution of S protein from animals to humans.",2006 Oct 4,"['Zhang, Chi-Yu', 'Wei, Ji-Fu', 'He, Shao-Heng']",BMC Microbiol,,,True
bdcfff55eaabeaa26d71810113d717ef85e417d1,PMC,MIMOX: a web tool for phage display based epitope mapping,http://dx.doi.org/10.1186/1471-2105-7-451,PMC1618411,17038191,CC BY,"BACKGROUND: Phage display is widely used in basic research such as the exploration of protein-protein interaction sites and networks, and applied research such as the development of new drugs, vaccines, and diagnostics. It has also become a promising method for epitope mapping. Research on new algorithms that assist and automate phage display based epitope mapping has attracted many groups. Most of the existing tools have not been implemented as an online service until now however, making it less convenient for the community to access, utilize, and evaluate them. RESULTS: We present MIMOX, a free web tool that helps to map the native epitope of an antibody based on one or more user supplied mimotopes and the antigen structure. MIMOX was coded in Perl using modules from the Bioperl project. It has two sections. In the first section, MIMOX provides a simple interface for ClustalW to align a set of mimotopes. It also provides a simple statistical method to derive the consensus sequence and embeds JalView as a Java applet to view and manage the alignment. In the second section, MIMOX can map a single mimotope or a consensus sequence of a set of mimotopes, on to the corresponding antigen structure and search for all of the clusters of residues that could represent the native epitope. NACCESS is used to evaluate the surface accessibility of the candidate clusters; and Jmol is embedded to view them interactively in their 3D context. Initial case studies show that MIMOX can reproduce mappings from existing tools such as FINDMAP and 3DEX, as well as providing novel, rational results. CONCLUSION: A web-based tool called MIMOX has been developed for phage display based epitope mapping. As a publicly available online service in this area, it is convenient for the community to access, utilize, and evaluate, complementing other existing programs. MIMOX is freely available at .",2006 Oct 12,"['Huang, Jian', 'Gutteridge, Alex', 'Honda, Wataru', 'Kanehisa, Minoru']",BMC Bioinformatics,,,True
da6d83da65e485c34b903968ae22da9efbd81628,PMC,Global response to pandemic flu: more research needed on a critical front,http://dx.doi.org/10.1186/1478-4505-4-8,PMC1618830,17038194,CC BY,"If and when sustained human-to-human transmission of H5N1 becomes a reality, the world will no longer be dealing with sporadic avian flu borne along migratory flight paths of birds, but aviation flu – winged at subsonic speed along commercial air conduits to every corner of planet Earth. Given that air transportation is the one feature that most differentiates present day transmission scenarios from those in 1918, our present inability to prevent spread of influenza by international air travel, as reckoned by the World Health Organization, constitutes a major weakness in the current global preparedness plan against pandemic flu. Despite the lessons of SARS, it is surprising that aviation-related health policy options have not been more rigorously evaluated, or scientific research aimed at strengthening public health measures on the air transportation front, more energetically pursued.",2006 Oct 13,"Lim, Meng-Kin",Health Res Policy Syst,,,True
ee1b5a9618dcc4080ed100486cedd0969e80fa4d,PMC,A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany,http://dx.doi.org/10.1186/1471-2334-6-147,PMC1618839,17026751,CC BY,"BACKGROUND: In May 2003 the Soest County Health Department was informed of an unusually large number of patients hospitalized with atypical pneumonia. METHODS: In exploratory interviews patients mentioned having visited a farmers' market where a sheep had lambed. Serologic testing confirmed the diagnosis of Q fever. We asked local health departments in Germany to identiy notified Q fever patients who had visited the farmers market. To investigate risk factors for infection we conducted a case control study (cases were Q fever patients, controls were randomly selected Soest citizens) and a cohort study among vendors at the market. The sheep exhibited at the market, the herd from which it originated as well as sheep from herds held in the vicinity of Soest were tested for Coxiella burnetii (C. burnetii). RESULTS: A total of 299 reported Q fever cases was linked to this outbreak. The mean incubation period was 21 days, with an interquartile range of 16–24 days. The case control study identified close proximity to and stopping for at least a few seconds at the sheep's pen as significant risk factors. Vendors within approximately 6 meters of the sheep's pen were at increased risk for disease compared to those located farther away. Wind played no significant role. The clinical attack rate of adults and children was estimated as 20% and 3%, respectively, 25% of cases were hospitalized. The ewe that had lambed as well as 25% of its herd tested positive for C. burnetii antibodies. CONCLUSION: Due to its size and point source nature this outbreak permitted assessment of fundamental, but seldom studied epidemiological parameters. As a consequence of this outbreak, it was recommended that pregnant sheep not be displayed in public during the 3(rd )trimester and to test animals in petting zoos regularly for C. burnetii.",2006 Oct 6,"['Porten, Klaudia', 'Rissland, Jürgen', 'Tigges, Almira', 'Broll, Susanne', 'Hopp, Wilfried', 'Lunemann, Mechthild', 'van Treeck, Ulrich', 'Kimmig, Peter', 'Brockmann, Stefan O', 'Wagner-Wiening, Christiane', 'Hellenbrand, Wiebke', 'Buchholz, Udo']",BMC Infect Dis,,,True
4b43f61d164be997a34343c11c70c42edd91898b,PMC,Distributed data processing for public health surveillance,http://dx.doi.org/10.1186/1471-2458-6-235,PMC1618842,16984658,CC BY,"BACKGROUND: Many systems for routine public health surveillance rely on centralized collection of potentially identifiable, individual, identifiable personal health information (PHI) records. Although individual, identifiable patient records are essential for conditions for which there is mandated reporting, such as tuberculosis or sexually transmitted diseases, they are not routinely required for effective syndromic surveillance. Public concern about the routine collection of large quantities of PHI to support non-traditional public health functions may make alternative surveillance methods that do not rely on centralized identifiable PHI databases increasingly desirable. METHODS: The National Bioterrorism Syndromic Surveillance Demonstration Program (NDP) is an example of one alternative model. All PHI in this system is initially processed within the secured infrastructure of the health care provider that collects and holds the data, using uniform software distributed and supported by the NDP. Only highly aggregated count data is transferred to the datacenter for statistical processing and display. RESULTS: Detailed, patient level information is readily available to the health care provider to elucidate signals observed in the aggregated data, or for ad hoc queries. We briefly describe the benefits and disadvantages associated with this distributed processing model for routine automated syndromic surveillance. CONCLUSION: For well-defined surveillance requirements, the model can be successfully deployed with very low risk of inadvertent disclosure of PHI – a feature that may make participation in surveillance systems more feasible for organizations and more appealing to the individuals whose PHI they hold. It is possible to design and implement distributed systems to support non-routine public health needs if required.",2006 Sep 19,"['Lazarus, Ross', 'Yih, Katherine', 'Platt, Richard']",BMC Public Health,,,True
ffe04775867d268ef18a29f13138e407b6aa8ea5,PMC,Clinical and epidemiological predictors of transmission in Severe Acute Respiratory Syndrome (SARS),http://dx.doi.org/10.1186/1471-2334-6-151,PMC1624840,17049088,CC BY,"BACKGROUND: Only a minority of probable SARS cases caused transmission. We assess if any epidemiological or clinical factors in SARS index patients were associated with increased probability of transmission. METHODS: We used epidemiological and clinical data on probable SARS patients admitted to Tan Tock Seng Hospital. Using a case-control approach, index patients who had probable SARS who subsequently transmitted the disease to at least one other patient were analysed as ""cases"" against patients with no transmission as ""controls"", using multivariate logistic regression analysis. RESULTS: 98 index patients were available for analysis (22 with transmission, 76 with no transmission). Covariates positively associated with transmission in univariate analysis at p < 0.05 included delay to isolation (Day 7 of illness or later), admission to a non-isolation facility, pre-existing chronic respiratory disease and immunosuppressive disease, need for oxygen, shortness of breath, vomiting, and higher lactate dehydrogenase levels and higher neutrophil counts. In the multivariate analysis, only three factors were significant: delay to isolation, admission to a non-isolation facility and higher lactate dehydrogenase levels of >650 IU/L (OR 6.4, 23.8 and 4.7 respectively). CONCLUSION: Clinical and epidemiological factors can help us to explain why transmission was observed in some instances but not in others.",2006 Oct 18,"['Chen, Mark IC', 'Chow, Angela LP', 'Earnest, Arul', 'Leong, Hoe Nam', 'Leo, Yee Sin']",BMC Infect Dis,,,True
0491da5ae5c2fa38824350bde5462ed82ebc24e7,PMC,Immunogenicity of a polyvalent HIV-1 candidate vaccine based on fourteen wild type gp120 proteins in golden hamsters,http://dx.doi.org/10.1186/1471-2172-7-25,PMC1636068,17076905,CC BY,"BACKGROUND: One of the major obstacles in the design of an effective vaccine against HIV-1 is the hypervariability of the HIV-1 envelope glycoprotein. Most HIV-1 vaccine candidates have utilized envelope glycoprotein from a single virus isolate, but to date, none of them elicited broadly reactive humoral immunity. Herein, we hypothesised that a cocktail of HIV-1 gp120 proteins containing multiple epitopes may increase the breadth of immune responses against HIV-1. We compared and evaluated the immunogenicity of HIV-1 vaccines containing either gp120 protein alone or in combinations of four or fourteen gp120s from different primary HIV-1 isolates in immunized hamsters. RESULTS: We amplified and characterized 14 different gp120s from primary subtype B isolates with both syncytium and non-syncytium inducing properties, and expressed the proteins in Chinese Hamster Ovary (CHO) cell lines. Purified proteins were used either alone or in combinations of four or fourteen different gp120s to vaccinate golden hamsters. The polyvalent vaccine showed higher antibody titers to HIV-1 subtype B isolates MN and SF162 compared to the groups that received one or four gp120 proteins. However, the polyvalent vaccine was not able to show higher neutralizing antibody responses against HIV-1 primary isolates. Interestingly, the polyvalent vaccine group had the highest proliferative immune responses and showed a substantial proportion of cross-subtype CD4 reactivity to HIV-1 subtypes B, C, and A/E CONCLUSION: Although the polyvalent approach achieved only a modest increase in the breadth of humoral and cellular immunity, the qualitative change in the vaccine (14 vs. 1 gp120) resulted in a quantitative improvement in vaccine-induced immunity.",2006 Oct 31,"['Azizi, Ali', 'Anderson, David E', 'Ghorbani, Masoud', 'Gee, Katrina', 'Diaz-Mitoma, Francisco']",BMC Immunol,,,True
c7d86587837b09a6b722f78beac7bfedaa0333d3,PMC,Structure-based discovery of inhibitors of the YycG histidine kinase: New chemical leads to combat Staphylococcus epidermidis infections,http://dx.doi.org/10.1186/1471-2180-6-96,PMC1660542,17094812,CC BY,"BACKGROUND: Coagulase-negative Staphylococcus epidermidis has become a major frequent cause of infections in relation to the use of implanted medical devices. The pathogenicity of S. epidermidis has been attributed to its capacity to form biofilms on surfaces of medical devices, which greatly increases its resistance to many conventional antibiotics and often results in chronic infection. It has an urgent need to design novel antibiotics against staphylococci infections, especially those can kill cells embedded in biofilm. RESULTS: In this report, a series of novel inhibitors of the histidine kinase (HK) YycG protein of S. epidermidis were discovered first using structure-based virtual screening (SBVS) from a small molecular lead-compound library, followed by experimental validation. Of the 76 candidates derived by SBVS targeting of the homolog model of the YycG HATPase_c domain of S. epidermidis, seven compounds displayed significant activity in inhibiting S. epidermidis growth. Furthermore, five of them displayed bactericidal effects on both planktonic and biofilm cells of S. epidermidis. Except for one, the compounds were found to bind to the YycG protein and to inhibit its auto-phosphorylation in vitro, indicating that they are potential inhibitors of the YycG/YycF two-component system (TCS), which is essential in S. epidermidis. Importantly, all these compounds did not affect the stability of mammalian cells nor hemolytic activities at the concentrations used in our study. CONCLUSION: These novel inhibitors of YycG histidine kinase thus are of potential value as leads for developing new antibiotics against infecting staphylococci. The structure-based virtual screening (SBVS) technology can be widely used in screening potential inhibitors of other bacterial TCSs, since it is more rapid and efficacious than traditional screening technology.",2006 Nov 10,"['Qin, Zhiqiang', 'Zhang, Jian', 'Xu, Bin', 'Chen, Lili', 'Wu, Yang', 'Yang, Xiaomei', 'Shen, Xu', 'Molin, Soeren', 'Danchin, Antoine', 'Jiang, Hualiang', 'Qu, Di']",BMC Microbiol,,,True
86fe00ed292aab3fd191a7f8253d33dad3be59b3,PMC,Distinct cellular responses differentiating alcohol- and hepatitis C virus-induced liver cirrhosis,http://dx.doi.org/10.1186/1743-422X-3-98,PMC1676004,17121680,CC BY,"BACKGROUND: Little is known at the molecular level concerning the differences and/or similarities between alcohol and hepatitis C virus induced liver disease. Global transcriptional profiling using oligonucleotide microarrays was therefore performed on liver biopsies from patients with cirrhosis caused by either chronic alcohol consumption or chronic hepatitis C virus (HCV). RESULTS: Global gene expression patterns varied significantly depending upon etiology of liver disease, with a greater number of differentially regulated genes seen in HCV-infected patients. Many of the gene expression changes specifically observed in HCV-infected cirrhotic livers were expectedly associated with activation of the innate antiviral immune response. We also compared severity (CTP class) of cirrhosis for each etiology and identified gene expression patterns that differentiated ethanol-induced cirrhosis by class. CTP class A ethanol-cirrhotic livers showed unique expression patterns for genes implicated in the inflammatory response, including those related to macrophage activation and migration, as well as lipid metabolism and oxidative stress genes. CONCLUSION: Stages of liver cirrhosis could be differentiated based on gene expression patterns in ethanol-induced, but not HCV-induced, disease. In addition to genes specifically regulating the innate antiviral immune response, mechanisms responsible for differentiating chronic liver damage due to HCV or ethanol may be closely related to regulation of lipid metabolism and to effects of macrophage activation on deposition of extracellular matrix components.",2006 Nov 22,"['Lederer, Sharon L', 'Walters, Kathie-Anne', 'Proll, Sean', 'Paeper, Bryan', 'Robinzon, Shahar', 'Boix, Loreto', 'Fausto, Nelson', 'Bruix, Jordi', 'Katze, Michael G']",Virol J,,,True
c878b060760db3b59ae0129a5de677e56a30866e,PMC,"Improving the use of research evidence in guideline development: 13. Applicability, transferability and adaptation",http://dx.doi.org/10.1186/1478-4505-4-25,PMC1712227,17156457,CC BY,"BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the thirteenth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on applicability, transferability, and adaptation of guidelines. METHODS: We searched five databases for existing systematic reviews and relevant primary methodological research. We reviewed the titles of all citations and retrieved abstracts and full text articles if the citations appeared relevant to the topic. We checked the reference lists of articles relevant to the questions and used snowballing as a technique to obtain additional information. We used the definition ""coming from, concerning or belonging to at least two or all nations"" for the term international. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: We did not identify systematic reviews addressing the key questions. We found individual studies and projects published in the peer reviewed literature and on the Internet. Should WHO develop international recommendations? • Resources for developing high quality recommendations are limited. Internationally developed recommendations can facilitate access to and pooling of resources, reduce unnecessary duplication, and involve international scientists. • Priority should be given to international health problems and problems that are important in low and middle-income countries, where these advantages are likely to be greatest. • Factors that influence the transferability of recommendations across different settings should be considered systematically and flagged, including modifying factors, important variation in needs, values, costs and the availability of resources. What should be done centrally and locally? • The preparation of systematic reviews and evidence profiles should be coordinated centrally, in collaboration with organizations that produce systematic reviews. Centrally developed evidence profiles should be adaptable to specific local circumstances. • Consideration should be given to models that involve central coordination with work being undertaken by centres located throughout the world. • While needs, availability of resources, costs, the presence of modifying factors and values need to be assessed locally, support for undertaking these assessments may be needed to make guidelines applicable. • WHO should provide local support for adapting and implementing recommendations by developing tools, building capacity, learning from international experience, and through international networks that support evidence-informed health policies, such as the Evidence-informed Policy Network (EVIPNet). How should recommendations be adapted? • WHO should provide detailed guidance for adaptation of international recommendations. • Local adaptation processes should be systematic and transparent, they should involve stakeholders, and they should report the key factors that influence decisions, including those flagged in international guidelines, and the reasons for any modifications that are made.",2006 Dec 8,"['Schünemann, Holger J', 'Fretheim, Atle', 'Oxman, Andrew D']",Health Res Policy Syst,,,True
4bf165f82a8648b69169a66114d29c690f0562e0,PMC,Modeling early recovery of physical function following hip and knee arthroplasty,http://dx.doi.org/10.1186/1471-2474-7-100,PMC1712335,17156487,CC BY,"BACKGROUND: Information on early recovery after arthroplasty is needed to help benchmark progress and make appropriate decisions concerning patient rehabilitation needs. The purpose of this study was to model early recovery of physical function in patients undergoing total hip (THA) and knee (TKA) arthroplasty, using physical performance and self-report measures. METHODS: A sample of convenience of 152 subjects completed testing, of which 69 (mean age: 66.77 ± 8.23 years) underwent THA and 83 (mean age: 60.25 ± 11.19 years) TKA. Postoperatively, patients were treated using standardized care pathways and rehabilitation protocols. Using a repeated measures design, patients were assessed at multiple time points over the first four postoperative months. Outcome measures included the Lower Extremity Function Scale (LEFS), the physical function subscale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC PF), the 6 minute walk test (6 MWT), timed up and go test (TUG) and a timed stair test (ST). Average recovery curves for each of the measures were characterized using hierarchical linear modeling. Predictors of recovery were sequentially modeled after validation of the basic developmental models. RESULTS: Slopes of recovery were greater in the first 6 to 9 weeks with a second-degree polynomial growth term (weeks squared) providing a reasonable fit for the data over the study interval. Different patterns of recovery were observed between the self-report measures of physical function and the performance measures. In contrast to the models for the WOMAC PF and the LEFS, site of arthroplasty was a significant predictor (p = 0.001) in all of the physical performance measure models with the patients post TKA initially demonstrating higher function. Site of arthroplasty (p = 0.025) also predicted the rate of change for patients post THA and between 9 to 11 weeks after surgery, the THA group surpassed the function of the patients post TKA. CONCLUSION: Knowledge about the predicted growth curves will assist clinicians in referencing patient progress, and determining the critical time points for measuring change. The study has contributed further evidence to highlight the benefit of using physical performance measures to learn about the patients' actual level of disability.",2006 Dec 11,"['Kennedy, Deborah M', 'Stratford, Paul W', 'Hanna, Steven E', 'Wessel, Jean', 'Gollish, Jeffrey D']",BMC Musculoskelet Disord,,,True
29b6131c0d572d383cbc6774b12e4471aa612b07,PMC,Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants,http://dx.doi.org/10.1371/journal.pmed.0030525,PMC1716185,17194199,CC BY,"BACKGROUND: In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) was identified as the etiological agent of severe acute respiratory syndrome, a disease characterized by severe pneumonia that sometimes results in death. SARS-CoV is a zoonotic virus that crossed the species barrier, most likely originating from bats or from other species including civets, raccoon dogs, domestic cats, swine, and rodents. A SARS-CoV vaccine should confer long-term protection, especially in vulnerable senescent populations, against both the 2003 epidemic strains and zoonotic strains that may yet emerge from animal reservoirs. We report the comprehensive investigation of SARS vaccine efficacy in young and senescent mice following homologous and heterologous challenge. METHODS AND FINDINGS: Using Venezuelan equine encephalitis virus replicon particles (VRP) expressing the 2003 epidemic Urbani SARS-CoV strain spike (S) glycoprotein (VRP-S) or the nucleocapsid (N) protein from the same strain (VRP-N), we demonstrate that VRP-S, but not VRP-N vaccines provide complete short- and long-term protection against homologous strain challenge in young and senescent mice. To test VRP vaccine efficacy against a heterologous SARS-CoV, we used phylogenetic analyses, synthetic biology, and reverse genetics to construct a chimeric virus (icGDO3-S) encoding a synthetic S glycoprotein gene of the most genetically divergent human strain, GDO3, which clusters among the zoonotic SARS-CoV. icGD03-S replicated efficiently in human airway epithelial cells and in the lungs of young and senescent mice, and was highly resistant to neutralization with antisera directed against the Urbani strain. Although VRP-S vaccines provided complete short-term protection against heterologous icGD03-S challenge in young mice, only limited protection was seen in vaccinated senescent animals. VRP-N vaccines not only failed to protect from homologous or heterologous challenge, but resulted in enhanced immunopathology with eosinophilic infiltrates within the lungs of SARS-CoV–challenged mice. VRP-N–induced pathology presented at day 4, peaked around day 7, and persisted through day 14, and was likely mediated by cellular immune responses. CONCLUSIONS: This study identifies gaps and challenges in vaccine design for controlling future SARS-CoV zoonosis, especially in vulnerable elderly populations. The availability of a SARS-CoV virus bearing heterologous S glycoproteins provides a robust challenge inoculum for evaluating vaccine efficacy against zoonotic strains, the most likely source of future outbreaks.",2006 Dec 26,"['Deming, Damon', 'Sheahan, Timothy', 'Heise, Mark', 'Yount, Boyd', 'Davis, Nancy', 'Sims, Amy', 'Suthar, Mehul', 'Harkema, Jack', 'Whitmore, Alan', 'Pickles, Raymond', 'West, Ande', 'Donaldson, Eric', 'Curtis, Kristopher', 'Johnston, Robert', 'Baric, Ralph']",PLoS Med,,,True
89eb2ddb11e00fa7652c170a84d919d2428d90f8,PMC,Epidemiology and clinical outcome of virus-positive respiratory samples in ventilated patients: a prospective cohort study,http://dx.doi.org/10.1186/cc5059,PMC1751045,17022805,CC BY,"INTRODUCTION: Respiratory viruses are a major cause of respiratory tract infections. The prevalence of a virus-positive respiratory sample and its significance in patients requiring mechanical ventilation remain unknown. METHODS: We conducted a cohort study in all consecutive adults ventilated for more than 48 hours admitted to a 22-bed medical intensive care unit during a 12-month period. Respiratory samples at the time of intubation were assessed by culture, by indirect immunofluorescence assay or by molecular methods in systematic tracheobronchial aspirates. Patients with a virus-negative respiratory sample at the time of intubation were considered unexposed and served as the control group. RESULTS: Forty-five viruses were isolated in 41/187 (22%) patients. Rhinovirus was the most commonly isolated virus (42%), followed byherpes simplex virus type 1 (22%) and virus influenza A (16%). In multivariate analysis controlling for the Acute Pathophysiology and Chronic Health Evaluation II score, patients with respiratory disorder at admission (adjusted odds ratio, 2.1; 95% confidence interval, 0.8–5.1; P = 0.12), with chronic obstructive pulmonary disease/asthma patients (adjusted odds ratio, 3.0; 95% confidence interval, 1.3–6.7; P = 0.01) and with admission between 21 November and 21 March (adjusted odds ratio, 2.8; 95% confidence interval, 1.3–5.9; P = 0.008) were independently associated with a virus-positive sample. Among the 122 patients admitted with respiratory disorder, a tracheobronchial aspirate positive for respiratory viruses at the time of intubation (adjusted hazard ratio, 0.273; 95% confidence interval, 0.096–0.777; P < 0.006) was independently associated with better survival, controlling for the Simplified Acute Physiology Score II and admission for cardiogenic shock or cardiac arrest. Among the remaining 65 patients, a virus-positive sample on intubation did not predict survival. CONCLUSION: We confirmed the pathogenic role of respiratory viruses in the intensive care unit, particularly rhinovirus. We suggest, however, that the prognostic value of virus-associated respiratory disorder is better than that of other causes of respiratory disorder.",2006 Oct 5,"['Daubin, Cédric', 'Parienti, Jean-Jacques', 'Vincent, Sophie', 'Vabret, Astrid', 'du Cheyron, Damien', 'Ramakers, Michel', 'Freymuth, François', 'Charbonneau, Pierre']",Crit Care,,,True
19717b7bfa9911835e3c0085633f6dec5453da9a,PMC,Societal Learning in Epidemics: Intervention Effectiveness during the 2003 SARS Outbreak in Singapore,http://dx.doi.org/10.1371/journal.pone.0000020,PMC1762333,17183647,CC BY,"BACKGROUND: Rapid response to outbreaks of emerging infectious diseases is impeded by uncertain diagnoses and delayed communication. Understanding the effect of inefficient response is a potentially important contribution of epidemic theory. To develop this understanding we studied societal learning during emerging outbreaks wherein patient removal accelerates as information is gathered and disseminated. METHODS AND FINDINGS: We developed an extension of a standard outbreak model, the simple stochastic epidemic, which accounts for societal learning. We obtained expressions for the expected outbreak size and the distribution of epidemic duration. We found that rapid learning noticeably affects the final outbreak size even when learning exhibits diminishing returns (relaxation). As an example, we estimated the learning rate for the 2003 outbreak of severe acute respiratory syndrome (SARS) in Singapore. Evidence for relaxation during the first eight weeks of the outbreak was inconclusive. We estimated that if societal learning had occurred at half the actual rate, the expected final size of the outbreak would have reached nearly 800 cases, more than three times the observed number of infections. By contrast, the expected outbreak size for societal learning twice as effective was 116 cases. CONCLUSION: These results show that the rate of societal learning can greatly affect the final size of disease outbreaks, justifying investment in early warning systems and attentiveness to disease outbreak by both government authorities and the public. We submit that the burden of emerging infections, including the risk of a global pandemic, could be efficiently reduced by improving procedures for rapid detection of outbreaks, alerting public health officials, and aggressively educating the public at the start of an outbreak.",2006 Dec 20,"['Drake, John M.', 'Chew, Suok Kai', 'Ma, Stefan']",PLoS One,,,True
c64f525d77bf8b2ae4439a875f1bd8eb197a0519,PMC,Association and Host Selectivity in Multi-Host Pathogens,http://dx.doi.org/10.1371/journal.pone.0000041,PMC1762347,17183670,CC BY,"The distribution of multi-host pathogens over their host range conditions their population dynamics and structure. Also, host co-infection by different pathogens may have important consequences for the evolution of hosts and pathogens, and host-pathogen co-evolution. Hence it is of interest to know if the distribution of pathogens over their host range is random, or if there are associations between hosts and pathogens, or between pathogens sharing a host. To analyse these issues we propose indices for the observed patterns of host infection by pathogens, and for the observed patterns of co-infection, and tests to analyse if these patterns conform to randomness or reflect associations. Applying these tests to the prevalence of five plant viruses on 21 wild plant species evidenced host-virus associations: most hosts and viruses were selective for viruses and hosts, respectively. Interestingly, the more host-selective viruses were the more prevalent ones, suggesting that host specialisation is a successful strategy for multi-host pathogens. Analyses also showed that viruses tended to associate positively in co-infected hosts. The developed indices and tests provide the tools to analyse how strong and common are these associations among different groups of pathogens, which will help to understand and model the population biology of multi-host pathogens.",2006 Dec 20,"['Malpica, José M.', 'Sacristán, Soledad', 'Fraile, Aurora', 'García-Arenal, Fernando']",PLoS One,,,True
389612b52a4489f9be2109a5eb0060499a0f7c15,PMC,Long-Term Persistence of Robust Antibody and Cytotoxic T Cell Responses in Recovered Patients Infected with SARS Coronavirus,http://dx.doi.org/10.1371/journal.pone.0000024,PMC1762349,17183651,CC BY,"Most of the individuals infected with SARS coronavirus (SARS-CoV) spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL) responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.",2006 Dec 20,"['Li, Taisheng', 'Xie, Jing', 'He, Yuxian', 'Fan, Hongwei', 'Baril, Laurence', 'Qiu, Zhifeng', 'Han, Yang', 'Xu, Wenbing', 'Zhang, Weihong', 'You, Hui', 'Zuo, Yanling', 'Fang, Qing', 'Yu, Jian', 'Chen, Zhiwei', 'Zhang, Linqi']",PLoS One,,,True
6af02873a430f5f75dc56a917f26feaea89b8e79,PMC,The Effectiveness of Contact Tracing in Emerging Epidemics,http://dx.doi.org/10.1371/journal.pone.0000012,PMC1762362,17183638,CC BY,"BACKGROUND: Contact tracing plays an important role in the control of emerging infectious diseases, but little is known yet about its effectiveness. Here we deduce from a generic mathematical model how effectiveness of tracing relates to various aspects of time, such as the course of individual infectivity, the (variability in) time between infection and symptom-based detection, and delays in the tracing process. In addition, the possibility of iteratively tracing of yet asymptomatic infecteds is considered. With these insights we explain why contact tracing was and will be effective for control of smallpox and SARS, only partially effective for foot-and-mouth disease, and likely not effective for influenza. METHODS AND FINDINGS: We investigate contact tracing in a model of an emerging epidemic that is flexible enough to use for most infections. We consider isolation of symptomatic infecteds as the basic scenario, and express effectiveness as the proportion of contacts that need to be traced for a reproduction ratio smaller than 1. We obtain general results for special cases, which are interpreted with respect to the likely success of tracing for influenza, smallpox, SARS, and foot-and-mouth disease epidemics. CONCLUSIONS: We conclude that (1) there is no general predictive formula for the proportion to be traced as there is for the proportion to be vaccinated; (2) variability in time to detection is favourable for effective tracing; (3) tracing effectiveness need not be sensitive to the duration of the latent period and tracing delays; (4) iterative tracing primarily improves effectiveness when single-step tracing is on the brink of being effective.",2006 Dec 20,"['Klinkenberg, Don', 'Fraser, Christophe', 'Heesterbeek, Hans']",PLoS One,,,True
7155c0fda843cfccdbd4bf302b1d7f2c343f528f,PMC,The Effectiveness of Contact Tracing in Emerging Epidemics,http://dx.doi.org/10.1371/journal.pone.0000012,PMC1762362,17183638,CC BY,"BACKGROUND: Contact tracing plays an important role in the control of emerging infectious diseases, but little is known yet about its effectiveness. Here we deduce from a generic mathematical model how effectiveness of tracing relates to various aspects of time, such as the course of individual infectivity, the (variability in) time between infection and symptom-based detection, and delays in the tracing process. In addition, the possibility of iteratively tracing of yet asymptomatic infecteds is considered. With these insights we explain why contact tracing was and will be effective for control of smallpox and SARS, only partially effective for foot-and-mouth disease, and likely not effective for influenza. METHODS AND FINDINGS: We investigate contact tracing in a model of an emerging epidemic that is flexible enough to use for most infections. We consider isolation of symptomatic infecteds as the basic scenario, and express effectiveness as the proportion of contacts that need to be traced for a reproduction ratio smaller than 1. We obtain general results for special cases, which are interpreted with respect to the likely success of tracing for influenza, smallpox, SARS, and foot-and-mouth disease epidemics. CONCLUSIONS: We conclude that (1) there is no general predictive formula for the proportion to be traced as there is for the proportion to be vaccinated; (2) variability in time to detection is favourable for effective tracing; (3) tracing effectiveness need not be sensitive to the duration of the latent period and tracing delays; (4) iterative tracing primarily improves effectiveness when single-step tracing is on the brink of being effective.",2006 Dec 20,"['Klinkenberg, Don', 'Fraser, Christophe', 'Heesterbeek, Hans']",PLoS One,,,False
57d2a2f022fc3ec32d1b92bb0a234c9f4ac8e1d6,PMC,DNA Encoding an HIV-1 Gag/Human Lysosome-Associated Membrane Protein-1 Chimera Elicits a Broad Cellular and Humoral Immune Response in Rhesus Macaques,http://dx.doi.org/10.1371/journal.pone.0000135,PMC1762437,17205139,CC BY,"Previous studies of HIV-1 p55Gag immunization of mice have demonstrated the usefulness of targeting antigens to the cellular compartment containing the major histocompatibility complex type II (MHC II) complex molecules by use of a DNA antigen formulation encoding Gag as a chimera with the mouse lysosome-associated membrane protein (mLAMP/gag). In the present study, we have analyzed the magnitude and breadth of Gag-specific T-lymphocyte and antibody responses elicited in Rhesus macaques after immunization with DNA encoding a human LAMP/gag (hLAMP/gag) chimera. ELISPOT analyses indicated that the average Gag-specific IFN-γ response elicited by the hLAMP/gag chimera was detectable after only two or three naked DNA immunizations in all five immunized macaques and reached an average of 1000 spot-forming cells (SFC)/10(6) PBMCs. High IFN-γ ELISPOT responses were detected in CD8(+)-depleted cells, indicating that CD4(+) T-cells play a major role in these responses. The T-cell responses of four of the macaques were also tested by use of ELISPOT to 12 overlapping 15-amino acids (aa) peptide pools containing ten peptides each, encompassing the complete Gag protein sequence. The two Mamu 08 immunized macaques responded to eight and twelve of the pools, the Mamu B01 to six, and the other macaque to five pools indicating that the hLAMP/gag DNA antigen formulation elicits a broad T-cell response against Gag. Additionally, there was a strong HIV-1-specific IgG response. The IgG antibody titers increased after each DNA injection, indicating a strong amnestic B-cell response, and were highly elevated in all the macaques after three immunizations. Moreover, the serum of each macaque recognized 13 of the 49 peptides of a 20-aa peptide library covering the complete Gag amino acid sequence. In addition, HIV-1-specific IgA antibodies were present in the plasma and external secretions, including nasal washes. These data support the findings of increased immunogenicity of genetic vaccines encoded as LAMP chimeras, including the response to DNA vaccines by non-human primates.",2006 Dec 27,"['Chikhlikar, Priya', 'de Arruda, Luciana Barros', 'Maciel, Milton', 'Silvera, Peter', 'Lewis, Mark G.', 'August, J. Thomas', 'Marques, Ernesto T.A.']",PLoS One,,,True
bcb21b0dcaf5456200446cd3e1c6ad1990253dbf,PMC,The effect of travel restrictions on the spread of a moderately contagious disease,http://dx.doi.org/10.1186/1741-7015-4-32,PMC1764026,17166291,CC BY,"BACKGROUND: Much research in epidemiology has been focused on evaluating conventional methods of control strategies in the event of an epidemic or pandemic. Travel restrictions are often suggested as an efficient way to reduce the spread of a contagious disease that threatens public health, but few papers have studied in depth the effects of travel restrictions. In this study, we investigated what effect different levels of travel restrictions might have on the speed and geographical spread of an outbreak of a disease similar to severe acute respiratory syndrome (SARS). METHODS: We used a stochastic simulation model incorporating survey data of travel patterns between municipalities in Sweden collected over 3 years. We tested scenarios of travel restrictions in which travel over distances >50 km and 20 km would be banned, taking into account different levels of compliance. RESULTS: We found that a ban on journeys >50 km would drastically reduce the speed and geographical spread of outbreaks, even when compliance is < 100%. The result was found to be robust for different rates of intermunicipality transmission intensities. CONCLUSION: This study supports travel restrictions as an effective way to mitigate the effect of a future disease outbreak.",2006 Dec 14,"['Camitz, Martin', 'Liljeros, Fredrik']",BMC Med,,,True
9b7a0ad7b6c7f59e7a6cf1dc9d07912a273d19b5,PMC,The Waiting Time for Inter-Country Spread of Pandemic Influenza,http://dx.doi.org/10.1371/journal.pone.0000143,PMC1764036,17206278,CC BY,"BACKGROUND: The time delay between the start of an influenza pandemic and its subsequent initiation in other countries is highly relevant to preparedness planning. We quantify the distribution of this random time in terms of the separate components of this delay, and assess how the delay may be extended by non-pharmaceutical interventions. METHODS AND FINDINGS: The model constructed for this time delay accounts for: (i) epidemic growth in the source region, (ii) the delay until an infected individual from the source region seeks to travel to an at-risk country, (iii) the chance that infected travelers are detected by screening at exit and entry borders, (iv) the possibility of in-flight transmission, (v) the chance that an infected arrival might not initiate an epidemic, and (vi) the delay until infection in the at-risk country gathers momentum. Efforts that reduce the disease reproduction number in the source region below two and severe travel restrictions are most effective for delaying a local epidemic, and under favourable circumstances, could add several months to the delay. On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks. Elevated in-flight transmission reduces the delay only minimally. CONCLUSIONS: The delay until an epidemic of pandemic strain influenza is imported into an at-risk country is largely determined by the course of the epidemic in the source region and the number of travelers attempting to enter the at-risk country, and is little affected by non-pharmaceutical interventions targeting these travelers. Short of preventing international travel altogether, eradicating a nascent pandemic in the source region appears to be the only reliable method of preventing country-to-country spread of a pandemic strain of influenza.",2007 Jan 3,"['Caley, Peter', 'Becker, Niels G.', 'Philp, David J.']",PLoS One,,,True
5ec4b4abb2bca7c9a189f466680e47fd5f56486e,PMC,The Waiting Time for Inter-Country Spread of Pandemic Influenza,http://dx.doi.org/10.1371/journal.pone.0000143,PMC1764036,17206278,CC BY,"BACKGROUND: The time delay between the start of an influenza pandemic and its subsequent initiation in other countries is highly relevant to preparedness planning. We quantify the distribution of this random time in terms of the separate components of this delay, and assess how the delay may be extended by non-pharmaceutical interventions. METHODS AND FINDINGS: The model constructed for this time delay accounts for: (i) epidemic growth in the source region, (ii) the delay until an infected individual from the source region seeks to travel to an at-risk country, (iii) the chance that infected travelers are detected by screening at exit and entry borders, (iv) the possibility of in-flight transmission, (v) the chance that an infected arrival might not initiate an epidemic, and (vi) the delay until infection in the at-risk country gathers momentum. Efforts that reduce the disease reproduction number in the source region below two and severe travel restrictions are most effective for delaying a local epidemic, and under favourable circumstances, could add several months to the delay. On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks. Elevated in-flight transmission reduces the delay only minimally. CONCLUSIONS: The delay until an epidemic of pandemic strain influenza is imported into an at-risk country is largely determined by the course of the epidemic in the source region and the number of travelers attempting to enter the at-risk country, and is little affected by non-pharmaceutical interventions targeting these travelers. Short of preventing international travel altogether, eradicating a nascent pandemic in the source region appears to be the only reliable method of preventing country-to-country spread of a pandemic strain of influenza.",2007 Jan 3,"['Caley, Peter', 'Becker, Niels G.', 'Philp, David J.']",PLoS One,,,False
bd9162d8379baef31b50aa17a7f553740aa28ba2,PMC,"Curation of viral genomes: challenges, applications and the way forward",http://dx.doi.org/10.1186/1471-2105-7-S5-S12,PMC1764468,17254296,CC BY,"BACKGROUND: Whole genome sequence data is a step towards generating the 'parts list' of life to understand the underlying principles of Biocomplexity. Genome sequencing initiatives of human and model organisms are targeted efforts towards understanding principles of evolution with an application envisaged to improve human health. These efforts culminated in the development of dedicated resources. Whereas a large number of viral genomes have been sequenced by groups or individuals with an interest to study antigenic variation amongst strains and species. These independent efforts enabled viruses to attain the status of 'best-represented taxa' with the highest number of genomes. However, due to lack of concerted efforts, viral genomic sequences merely remained as entries in the public repositories until recently. RESULTS: VirGen is a curated resource of viral genomes and their analyses. Since its first release, it has grown both in terms of coverage of viral families and development of new modules for annotation and analysis. The current release (2.0) includes data for twenty-five families with broad host range as against eight in the first release. The taxonomic description of viruses in VirGen is in accordance with the ICTV nomenclature. A well-characterised strain is identified as a 'representative entry' for every viral species. This non-redundant dataset is used for subsequent annotation and analyses using sequenced-based Bioinformatics approaches. VirGen archives precomputed data on genome and proteome comparisons. A new data module that provides structures of viral proteins available in PDB has been incorporated recently. One of the unique features of VirGen is predicted conformational and sequential epitopes of known antigenic proteins using in-house developed algorithms, a step towards reverse vaccinology. CONCLUSION: Structured organization of genomic data facilitates use of data mining tools, which provides opportunities for knowledge discovery. One of the approaches to achieve this goal is to carry out functional annotations using comparative genomics. VirGen, a comprehensive viral genome resource that serves as an annotation and analysis pipeline has been developed for the curation of public domain viral genome data . Various steps in the curation and annotation of the genomic data and applications of the value-added derived data are substantiated with case studies.",2006 Dec 18,"['Kulkarni-Kale, Urmila', 'Bhosle, Shriram G', 'Manjari, G Sunitha', 'Joshi, Manali', 'Bansode, Sandeep', 'Kolaskar, Ashok S']",BMC Bioinformatics,,,True
b8e80e078c91d674918e69168da4085a9e176053,PMC,Influenza pandemic and professional duty: family or patients first? A survey of hospital employees,http://dx.doi.org/10.1186/1471-2458-6-311,PMC1764890,17192198,CC BY,"BACKGROUND: Conflicts between professional duties and fear of influenza transmission to family members may arise among health care professionals (HCP). METHODS: We surveyed employees at our university hospital regarding ethical issues arising during the management of an influenza pandemic. RESULTS: Of 644 respondents, 182 (28%) agreed that it would be professionally acceptable for HCP to abandon their workplace during a pandemic in order to protect themselves and their families, 337 (52%) disagreed with this statement and 125 (19%) had no opinion, with a higher rate of disagreement among physicians (65%) and nurses (54%) compared with administrators (32%). Of all respondents, 375 (58%) did not believe that the decision to report to work during a pandemic should be left to the individual HCP and 496 (77%) disagreed with the statement that HCP should be permanently dismissed for not reporting to work during a pandemic. Only 136 (21%) respondents agreed that HCW without children should primarily care for the influenza patients. CONCLUSION: Our results suggest that a modest majority of HCP, but only a minority of hospital administrators, recognises the obligation to treat patients despite the potential risks. Professional ethical guidelines allowing for balancing the needs of society with personal risks are needed to help HCP fulfil their duties in the case of a pandemic influenza.",2006 Dec 28,"['Ehrenstein, Boris P', 'Hanses, Frank', 'Salzberger, Bernd']",BMC Public Health,,,True
fa84d62d8e80e07fdcd1f5543bec8c3f2cb46b74,PMC,Mycoplasma alkalescens demonstrated in bronchoalveolar lavage of cattle in Denmark,http://dx.doi.org/10.1186/1751-0147-49-2,PMC1766361,17204146,CC BY,"Mycoplasma alkalescens is an arginine-metabolizing mycoplasma, which has been found in association with mastitis and arthritis in cattle. Routine bacteriological examination of 17 bronchoalveolar lavage samples from calves with pneumonia in a single herd in Denmark, identified M. alkalescens in eight samples. The organism was found as a sole bacterilogical findings in five of the samples as well as in combination with Mannheimia haemolytica, Haemophilus somni and Salmonella Dublin. This is the first report of isolation of M. alkalescens in Denmark.",2007 Jan 4,"['Kokotovic, Branko', 'Friis, Niels F', 'Ahrens, Peter']",Acta Vet Scand,,,True
4b9911544622c1028499e1db9cf9fb783c2ed863,PMC,"Proteomic Profiling of the Amniotic Fluid to Detect Inflammation, Infection, and Neonatal Sepsis",http://dx.doi.org/10.1371/journal.pmed.0040018,PMC1769412,17227133,CC BY,"BACKGROUND: Proteomic analysis of amniotic fluid shows the presence of biomarkers characteristic of intrauterine inflammation. We sought to validate prospectively the clinical utility of one such proteomic profile, the Mass Restricted (MR) score. METHODS AND FINDINGS: We enrolled 169 consecutive women with singleton pregnancies admitted with preterm labor or preterm premature rupture of membranes. All women had a clinically indicated amniocentesis to rule out intra-amniotic infection. A proteomic fingerprint (MR score) was generated from fresh samples of amniotic fluid using surface-enhanced laser desorption ionization (SELDI) mass spectrometry. Presence or absence of the biomarkers of the MR score was interpreted in relationship to the amniocentesis-to-delivery interval, placental inflammation, and early-onset neonatal sepsis for all neonates admitted to the Newborn Special Care Unit (n = 104). Women with “severe” amniotic fluid inflammation (MR score of 3 or 4) had shorter amniocentesis-to-delivery intervals than women with “no” (MR score of 0) inflammation or even “minimal” (MR score of 1 or 2) inflammation (median [range] MR 3–4: 0.4 d [0.0–49.6 d] versus MR 1–2: 3.8 d [0.0–151.2 d] versus MR 0: 17.0 d [0.1–94.3 d], p < 0.001). Nonetheless, a “minimal” degree of inflammation was also associated with preterm birth regardless of membrane status. There was a significant association between the MR score and severity of histological chorioamnionitis (r = 0.599, p < 0.001). Furthermore, neonatal hematological indices and early-onset sepsis significantly correlated with the MR score even after adjusting for gestational age at birth (OR for MR 3–4: 3.3 [95% CI, 1.1 to 9.2], p = 0.03). When compared with other laboratory tests routinely used to diagnose amniotic fluid inflammation and infection, the MR score had the highest accuracy to detect inflammation (white blood cell count > 100 cells/mm(3)), whereas the combination of Gram stain and MR score was best for rapid prediction of intra-amniotic infection (positive amniotic fluid culture). CONCLUSIONS: High MR scores are associated with preterm delivery, histological chorioamnionitis, and early-onset neonatal sepsis. In this study, proteomic analysis of amniotic fluid was shown to be the most accurate test for diagnosis of intra-amniotic inflammation, whereas addition of the MR score to the Gram stain provides the best combination of tests to rapidly predict infection.",2007 Jan 16,"['Buhimschi, Catalin S', 'Bhandari, Vineet', 'Hamar, Benjamin D', 'Bahtiyar, Mert-Ozan', 'Zhao, Guomao', 'Sfakianaki, Anna K', 'Pettker, Christian M', 'Magloire, Lissa', 'Funai, Edmund', 'Norwitz, Errol R', 'Paidas, Michael', 'Copel, Joshua A', 'Weiner, Carl P', 'Lockwood, Charles J', 'Buhimschi, Irina A']",PLoS Med,,,True
979eb6ed6241fecc3000a963222725a6439b2e19,PMC,Human coronavirus 229E encodes a single ORF4 protein between the spike and the envelope genes,http://dx.doi.org/10.1186/1743-422X-3-106,PMC1774570,17194306,CC BY,"BACKGROUND: The genome of coronaviruses contains structural and non-structural genes, including several so-called accessory genes. All group 1b coronaviruses encode a single accessory protein between the spike and envelope genes, except for human coronavirus (HCoV) 229E. The prototype virus has a split gene, encoding the putative ORF4a and ORF4b proteins. To determine whether primary HCoV-229E isolates exhibit this unusual genome organization, we analyzed the ORF4a/b region of five current clinical isolates from The Netherlands and three early isolates collected at the Common Cold Unit (CCU) in Salisbury, UK. RESULTS: All Dutch isolates were identical in the ORF4a/b region at amino acid level. All CCU isolates are only 98% identical to the Dutch isolates at the nucleotide level, but more closely related to the prototype HCoV-229E (>98%). Remarkably, our analyses revealed that the laboratory adapted, prototype HCoV-229E has a 2-nucleotide deletion in the ORF4a/b region, whereas all clinical isolates carry a single ORF, 660 nt in size, encoding a single protein of 219 amino acids, which is a homologue of the ORF3 proteins encoded by HCoV-NL63 and PEDV. CONCLUSION: Thus, the genome organization of the group 1b coronaviruses HCoV-NL63, PEDV and HCoV-229E is identical. It is possible that extensive culturing of the HCoV-229E laboratory strain resulted in truncation of ORF4. This may indicate that the protein is not essential in cell culture, but the highly conserved amino acid sequence of the ORF4 protein among clinical isolates suggests that the protein plays an important role in vivo.",2006 Dec 28,"['Dijkman, Ronald', 'Jebbink, Maarten F', 'Wilbrink, Berry', 'Pyrc, Krzysztof', 'Zaaijer, Hans L', 'Minor, Philip D', 'Franklin, Sally', 'Berkhout, Ben', 'Thiel, Volker', 'van der Hoek, Lia']",Virol J,,,True
b6353f8b0fcd86c2fd1e6f27c9b18a3ccc07980b,PMC,Neutralizing Antibody Fails to Impact the Course of Ebola Virus Infection in Monkeys,http://dx.doi.org/10.1371/journal.ppat.0030009,PMC1779296,17238286,CC0,"Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. In this study, we have investigated the ability of the neutralizing human monoclonal antibody, KZ52, to protect against Ebola virus in rhesus macaques. This antibody was previously shown to fully protect guinea pigs from infection. Four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody KZ52 intravenously 1 d before challenge with 1,000 plaque-forming units of Ebola virus, followed by a second dose of 50 mg/kg antibody 4 d after challenge. A control animal was exposed to virus in the absence of antibody treatment. Passive transfer of the neutralizing human monoclonal antibody not only failed to protect macaques against challenge with Ebola virus but also had a minimal effect on the explosive viral replication following infection. We show that the inability of antibody to impact infection was not due to neutralization escape. It appears that Ebola virus has a mechanism of infection propagation in vivo in macaques that is uniquely insensitive even to high concentrations of neutralizing antibody.",2007 Jan 19,"['Oswald, Wendelien B', 'Geisbert, Thomas W', 'Davis, Kelly J', 'Geisbert, Joan B', 'Sullivan, Nancy J', 'Jahrling, Peter B', 'Parren, Paul W. H. I', 'Burton, Dennis R']",PLoS Pathog,,,True
4b2b67b0f48b99e75c190ad11bc215bb5f27503f,PMC,XDR-TB in South Africa: No Time for Denial or Complacency,http://dx.doi.org/10.1371/journal.pmed.0040050,PMC1779818,17253901,CC BY,"Singh and colleagues discuss the threat to regional and global public health posed by XDR-TB in KwaZulu-Natal, and propose new measures to control the outbreak.",2007 Jan 23,"['Singh, Jerome Amir', 'Upshur, Ross', 'Padayatchi, Nesri']",PLoS Med,,,True
fbad56e66ee9453d193dfbbd775248044e0af261,PMC,GraphDNA: a Java program for graphical display of DNA composition analyses,http://dx.doi.org/10.1186/1471-2105-8-21,PMC1783863,17244370,CC BY,"BACKGROUND: Under conditions of no strand bias the number of Gs is equal to that of Cs for each DNA strand; similarly, the total number of Ts is equal to that of As. However, within each strand there are considerable local deviations from the A = T and G = C equality. These asymmetries in nucleotide composition have been extensively analyzed in prokaryotic and eukaryotic genomes and related to chromosome organization, transcription orientation and other processes in certain organisms. To carry out analysis of intra-strand nucleotide distribution several graphical methods have been developed. RESULTS: GraphDNA is a new Java application that provides a simple, user-friendly interface for the visualization of DNA nucleotide composition. The program accepts GenBank, EMBL and FASTA files as an input, and it displays multiple DNA nucleotide composition graphs (skews and walks) in a single window to allow direct comparisons between the sequences. We illustrate the use of DNA skews for characterization of poxvirus and coronavirus genomes. CONCLUSION: GraphDNA is a platform-independent, Open Source, tool for the analysis of nucleotide trends in DNA sequences. Multiple sequence formats can be read and multiple sequences may be plotted in a single results window.",2007 Jan 23,"['Thomas, Jamie M', 'Horspool, Daniel', 'Brown, Gordon', 'Tcherepanov, Vasily', 'Upton, Chris']",BMC Bioinformatics,,,True
247d3262ad1b15f331a89f70eec56b34dbe6b8b5,PMC,"Maximum Likelihood Estimation of the Negative Binomial Dispersion Parameter for Highly Overdispersed Data, with Applications to Infectious Diseases",http://dx.doi.org/10.1371/journal.pone.0000180,PMC1791715,17299582,CC BY,"BACKGROUND: The negative binomial distribution is used commonly throughout biology as a model for overdispersed count data, with attention focused on the negative binomial dispersion parameter, k. A substantial literature exists on the estimation of k, but most attention has focused on datasets that are not highly overdispersed (i.e., those with k≥1), and the accuracy of confidence intervals estimated for k is typically not explored. METHODOLOGY: This article presents a simulation study exploring the bias, precision, and confidence interval coverage of maximum-likelihood estimates of k from highly overdispersed distributions. In addition to exploring small-sample bias on negative binomial estimates, the study addresses estimation from datasets influenced by two types of event under-counting, and from disease transmission data subject to selection bias for successful outbreaks. CONCLUSIONS: Results show that maximum likelihood estimates of k can be biased upward by small sample size or under-reporting of zero-class events, but are not biased downward by any of the factors considered. Confidence intervals estimated from the asymptotic sampling variance tend to exhibit coverage below the nominal level, with overestimates of k comprising the great majority of coverage errors. Estimation from outbreak datasets does not increase the bias of k estimates, but can add significant upward bias to estimates of the mean. Because k varies inversely with the degree of overdispersion, these findings show that overestimation of the degree of overdispersion is very rare for these datasets.",2007 Feb 14,"Lloyd-Smith, James O.",PLoS One,,,True
c34dcfec2a5e68f31f6a0401d2cd636021d984bc,PMC,ProCAT: a data analysis approach for protein microarrays,http://dx.doi.org/10.1186/gb-2006-7-11-r110,PMC1794587,17109749,CC BY,"Protein microarrays provide a versatile method for the analysis of many protein biochemical activities. Existing DNA microarray analytical methods do not translate to protein microarrays due to differences between the technologies. Here we report a new approach, ProCAT, which corrects for background bias and spatial artifacts, identifies significant signals, filters nonspecific spots, and normalizes the resulting signal to protein abundance. ProCAT provides a powerful and flexible new approach for analyzing many types of protein microarrays.",2006 Nov 16,"['Zhu, Xiaowei', 'Gerstein, Mark', 'Snyder, Michael']",Genome Biol,,,True
3e8d47918fb2187af3e556eaf1d5e343f42b0c06,PMC,Quantification of human bocavirus in lower respiratory tract infections in China,http://dx.doi.org/10.1186/1750-9378-2-3,PMC1796861,17266760,CC BY,"A quantitative PCR method was established to quantify human bocavirus (HBoV) genomic copies in clinical specimens from children with lower respiratory tract infections (LRTI) in China. A total of 257 respiratory tract specimens were tested, and 7 (2.7%) of these (all sputum samples) were positive, with genomic copies that ranged from 8.0 × 10(3 )to 8.0 × 10(9 )in the samples. The main clinical symptom of patients who were positive for HBoV DNA was a pneumonia-like syndrome represented by high fever and cough. Our results suggest that HBoV may be an important etiological agent of LRTI in children in China.",2007 Jan 31,"['Lin, Feng', 'Zeng, Aiping', 'Yang, Ningmin', 'Lin, Haiyan', 'Yang, En', 'Wang, Shengqi', 'Pintel, David', 'Qiu, Jianming']",Infect Agent Cancer,,,True
5c29db6b02088e3b38e416bf32f6a02dbcf9cdf8,PMC,"A perspective on microarrays: current applications, pitfalls, and potential uses",http://dx.doi.org/10.1186/1475-2859-6-4,PMC1796898,17254338,CC BY,"With advances in robotics, computational capabilities, and the fabrication of high quality glass slides coinciding with increased genomic information being available on public databases, microarray technology is increasingly being used in laboratories around the world. In fact, fields as varied as: toxicology, evolutionary biology, drug development and production, disease characterization, diagnostics development, cellular physiology and stress responses, and forensics have benefiting from its use. However, for many researchers not familiar with microarrays, current articles and reviews often address neither the fundamental principles behind the technology nor the proper designing of experiments. Although, microarray technology is relatively simple, conceptually, its practice does require careful planning and detailed understanding of the limitations inherently present. Without these considerations, it can be exceedingly difficult to ascertain valuable information from microarray data. Therefore, this text aims to outline key features in microarray technology, paying particular attention to current applications as outlined in recent publications, experimental design, statistical methods, and potential uses. Furthermore, this review is not meant to be comprehensive, but rather substantive; highlighting important concepts and detailing steps necessary to conduct and interpret microarray experiments. Collectively, the information included in this text will highlight the versatility of microarray technology and provide a glimpse of what the future may hold.",2007 Jan 25,"['Jaluria, Pratik', 'Konstantopoulos, Konstantinos', 'Betenbaugh, Michael', 'Shiloach, Joseph']",Microb Cell Fact,,,True
ab40400780c96601bae9d2f4d1c317dc3322f865,PMC,Characterization of a Structural Intermediate of Flavivirus Membrane Fusion,http://dx.doi.org/10.1371/journal.ppat.0030020,PMC1797619,17305426,CC BY,"Viral membrane fusion proceeds through a sequence of steps that are driven by triggered conformational changes of viral envelope glycoproteins, so-called fusion proteins. Although high-resolution structural snapshots of viral fusion proteins in their prefusion and postfusion conformations are available, it has been difficult to define intermediate structures of the fusion pathway because of their transient nature. Flaviviruses possess a class II viral fusion protein (E) mediating fusion at acidic pH that is converted from a dimer to a trimer with a hairpin-like structure during the fusion process. Here we show for tick-borne encephalitis virus that exposure of virions to alkaline instead of acidic pH traps the particles in an intermediate conformation in which the E dimers dissociate and interact with target membranes via the fusion peptide without proceeding to the merger of the membranes. Further treatment to low pH, however, leads to fusion, suggesting that these monomers correspond to an as-yet-elusive intermediate required to convert the prefusion dimer into the postfusion trimer. Thus, the use of nonphysiological conditions allows a dissection of the flavivirus fusion process and the identification of two separate steps, in which membrane insertion of multiple copies of E monomers precedes the formation of hairpin-like trimers. This sequence of events provides important new insights for understanding the dynamic process of viral membrane fusion.",2007 Feb 16,"['Stiasny, Karin', 'Kössl, Christian', 'Lepault, Jean', 'Rey, Félix A', 'Heinz, Franz X']",PLoS Pathog,,,True
78b25bce9665a46183274a25151de342c9799ef3,PMC,Appropriate 'housekeeping' genes for use in expression profiling the effects of environmental estrogens in fish,http://dx.doi.org/10.1186/1471-2199-8-10,PMC1802086,17288598,CC BY,"BACKGROUND: Attempts to develop a mechanistic understanding of the effects of environmental estrogens on fish are increasingly conducted at the level of gene expression. Appropriate application of real-time PCR in such studies requires the use of a stably expressed 'housekeeping' gene as an internal control to normalize for differences in the amount of starting template between samples. RESULTS: We sought to identify appropriate genes for use as internal controls in experimental treatments with estrogen by analyzing the expression of eight functionally distinct 'housekeeping' genes (18S ribosomal RNA [18S rRNA], ribosomal protein l8 [rpl8], elongation factor 1 alpha [ef1a], glucose-6-phosphate dehydrogenase [g6pd], beta actin [bactin], glyceraldehyde-3-phosphate dehydrogenase [gapdh], hypoxanthine phosphoribosyltransferase 1 [hprt1], and tata box binding protein [tbp]) following exposure to the environmental estrogen, 17α-ethinylestradiol (EE(2)), in the fathead minnow (Pimephales promelas). Exposure to 10 ng/L EE(2 )for 21 days down-regulated the expression of ef1a, g6pd, bactin and gapdh in the liver, and bactin and gapdh in the gonad. Some of these effects were gender-specific, with bactin in the liver and gapdh in the gonad down-regulated by EE(2 )in males only. Furthermore, when ef1a, g6pd, bactin or gapdh were used for normalization, the hepatic expression of two genes of interest, vitellogenin (vtg) and cytochrome P450 1A (cyp1a) following exposure to EE(2 )was overestimated. CONCLUSION: Based on the data presented, we recommend 18S rRNA, rpl8, hprt1 and/or tbp, but not ef1a, g6pd, bactin and/or gapdh, as likely appropriate internal controls in real-time PCR studies of estrogens effects in fish. Our studies show that pre-validation of control genes considering the scope and nature of the experiments to be performed, including both gender and tissue type, is critical for accurate assessments of the effects of environmental estrogens on gene expression in fish.",2007 Feb 8,"['Filby, Amy L', 'Tyler, Charles R']",BMC Mol Biol,,,True
6ac1ceb6e591c8901e4cc265fcba2d9727607942,PMC,Appropriate 'housekeeping' genes for use in expression profiling the effects of environmental estrogens in fish,http://dx.doi.org/10.1186/1471-2199-8-10,PMC1802086,17288598,CC BY,"BACKGROUND: Attempts to develop a mechanistic understanding of the effects of environmental estrogens on fish are increasingly conducted at the level of gene expression. Appropriate application of real-time PCR in such studies requires the use of a stably expressed 'housekeeping' gene as an internal control to normalize for differences in the amount of starting template between samples. RESULTS: We sought to identify appropriate genes for use as internal controls in experimental treatments with estrogen by analyzing the expression of eight functionally distinct 'housekeeping' genes (18S ribosomal RNA [18S rRNA], ribosomal protein l8 [rpl8], elongation factor 1 alpha [ef1a], glucose-6-phosphate dehydrogenase [g6pd], beta actin [bactin], glyceraldehyde-3-phosphate dehydrogenase [gapdh], hypoxanthine phosphoribosyltransferase 1 [hprt1], and tata box binding protein [tbp]) following exposure to the environmental estrogen, 17α-ethinylestradiol (EE(2)), in the fathead minnow (Pimephales promelas). Exposure to 10 ng/L EE(2 )for 21 days down-regulated the expression of ef1a, g6pd, bactin and gapdh in the liver, and bactin and gapdh in the gonad. Some of these effects were gender-specific, with bactin in the liver and gapdh in the gonad down-regulated by EE(2 )in males only. Furthermore, when ef1a, g6pd, bactin or gapdh were used for normalization, the hepatic expression of two genes of interest, vitellogenin (vtg) and cytochrome P450 1A (cyp1a) following exposure to EE(2 )was overestimated. CONCLUSION: Based on the data presented, we recommend 18S rRNA, rpl8, hprt1 and/or tbp, but not ef1a, g6pd, bactin and/or gapdh, as likely appropriate internal controls in real-time PCR studies of estrogens effects in fish. Our studies show that pre-validation of control genes considering the scope and nature of the experiments to be performed, including both gender and tissue type, is critical for accurate assessments of the effects of environmental estrogens on gene expression in fish.",2007 Feb 8,"['Filby, Amy L', 'Tyler, Charles R']",BMC Mol Biol,,,False
9c8db583cc30937e746619bc3ffeda877f2a6369,PMC,Appropriate 'housekeeping' genes for use in expression profiling the effects of environmental estrogens in fish,http://dx.doi.org/10.1186/1471-2199-8-10,PMC1802086,17288598,CC BY,"BACKGROUND: Attempts to develop a mechanistic understanding of the effects of environmental estrogens on fish are increasingly conducted at the level of gene expression. Appropriate application of real-time PCR in such studies requires the use of a stably expressed 'housekeeping' gene as an internal control to normalize for differences in the amount of starting template between samples. RESULTS: We sought to identify appropriate genes for use as internal controls in experimental treatments with estrogen by analyzing the expression of eight functionally distinct 'housekeeping' genes (18S ribosomal RNA [18S rRNA], ribosomal protein l8 [rpl8], elongation factor 1 alpha [ef1a], glucose-6-phosphate dehydrogenase [g6pd], beta actin [bactin], glyceraldehyde-3-phosphate dehydrogenase [gapdh], hypoxanthine phosphoribosyltransferase 1 [hprt1], and tata box binding protein [tbp]) following exposure to the environmental estrogen, 17α-ethinylestradiol (EE(2)), in the fathead minnow (Pimephales promelas). Exposure to 10 ng/L EE(2 )for 21 days down-regulated the expression of ef1a, g6pd, bactin and gapdh in the liver, and bactin and gapdh in the gonad. Some of these effects were gender-specific, with bactin in the liver and gapdh in the gonad down-regulated by EE(2 )in males only. Furthermore, when ef1a, g6pd, bactin or gapdh were used for normalization, the hepatic expression of two genes of interest, vitellogenin (vtg) and cytochrome P450 1A (cyp1a) following exposure to EE(2 )was overestimated. CONCLUSION: Based on the data presented, we recommend 18S rRNA, rpl8, hprt1 and/or tbp, but not ef1a, g6pd, bactin and/or gapdh, as likely appropriate internal controls in real-time PCR studies of estrogens effects in fish. Our studies show that pre-validation of control genes considering the scope and nature of the experiments to be performed, including both gender and tissue type, is critical for accurate assessments of the effects of environmental estrogens on gene expression in fish.",2007 Feb 8,"['Filby, Amy L', 'Tyler, Charles R']",BMC Mol Biol,,,False
af3a11d67c66163d0c0fc185b497e21e55765047,PMC,Correction: Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants,http://dx.doi.org/10.1371/journal.pmed.0040080,PMC1808101,,CC BY,,2007 Feb 27,"['Deming, Damon', 'Sheahan, Timothy', 'Heise, Mark', 'Yount, Boyd', 'Davis, Nancy', 'Sims, Amy', 'Suthar, Mehul', 'Harkema, Jack', 'Whitmore, Alan', 'Pickles, Raymond', 'West, Ande', 'Donaldson, Eric', 'Curtis, Kristopher', 'Johnston, Robert', 'Baric, Ralph']",PLoS Med,,,False
e39c8a18a3d59b83951c4ebc331c17a54e6dacab,PMC,Pathogeneses of respiratory infections with virulent and attenuated vaccinia viruses,http://dx.doi.org/10.1186/1743-422X-4-22,PMC1810241,17326843,CC BY,"BACKGROUND: Respiratory infection with the neurovirulent vaccinia virus (VV) strain Western Reserve (WR) results in an acute infection of the lung followed by dissemination of the virus to other organs and causes lethality in mice. The mechanisms of lethality are not well-understood. In this study, we analyzed virus replication and host immune responses after intranasal infection with lethal and non-lethal doses of VV using the WR strain and the less virulent Wyeth strain. RESULTS: The WR strain replicated more vigorously in the lung and in the brain than the Wyeth strain. There were, however, no differences between the virus titers in the brains of mice infected with the higher lethal dose and the lower non-lethal dose of WR strain, suggesting that the amount of virus replication in the brain is unlikely to be the sole determining factor of lethality. The WR strain grew better in primary mouse lung cells than the Wyeth strain. Lethal infection with WR strain was associated with a reduced number of lymphocytes and an altered phenotype of the T cells in the lung compared to non-lethal infections with the WR or Wyeth strains. Severe thymus atrophy with a reduction of CD4 and CD8 double positive T cells was also observed in the lethal infection. CONCLUSION: These results suggest that the lethality induced by intranasal infection with a high dose of the WR strain is caused by the higher replication of virus in lung cells and immune suppression during the early phase of the infection, resulting in uncontrolled virus replication in the lung.",2007 Feb 27,"['Hayasaka, Daisuke', 'Ennis, Francis A', 'Terajima, Masanori']",Virol J,,,True
2cb893552a3e4a8aa105a96476b02c16bf7bef42,PMC,Feline aminopeptidase N is not a functional receptor for avian infectious bronchitis virus,http://dx.doi.org/10.1186/1743-422X-4-20,PMC1810517,17324273,CC BY,"BACKGROUND: Coronaviruses are an important cause of infectious diseases in humans, including severe acute respiratory syndrome (SARS), and have the continued potential for emergence from animal species. A major factor in the host range of a coronavirus is its receptor utilization on host cells. In many cases, coronavirus-receptor interactions are well understood. However, a notable exception is the receptor utilization by group 3 coronaviruses, including avian infectious bronchitis virus (IBV). Feline aminopeptidase N (fAPN) serves as a functional receptor for most group 1 coronaviruses including feline infectious peritonitis virus (FIPV), canine coronavirus, transmissible gastroenteritis virus (TGEV), and human coronavirus 229E (HCoV-229E). A recent report has also suggested a role for fAPN during IBV entry (Miguel B, Pharr GT, Wang C: The role of feline aminopeptidase N as a receptor for infectious bronchitis virus. Brief review. Arch Virol 2002, 147:2047–2056. RESULTS: Here we show that, whereas both transient transfection and constitutive expression of fAPN on BHK-21 cells can rescue FIPV and TGEV infection in non-permissive BHK cells, fAPN expression does not rescue infection by the prototype IBV strain Mass41. To account for the previous suggestion that fAPN could serve as an IBV receptor, we show that feline cells can be infected with the prototype strain of IBV (Mass 41), but with low susceptibility compared to primary chick kidney cells. We also show that BHK-21 cells are slightly susceptible to certain IBV strains, including Ark99, Ark_DPI, CA99, and Iowa97 (<0.01% efficiency), but this level of infection is not increased by fAPN expression. CONCLUSION: We conclude that fAPN is not a functional receptor for IBV, the identity of which is currently under investigation.",2007 Feb 26,"['Chu, Victor C', 'McElroy, Lisa J', 'Aronson, Jed M', 'Oura, Trisha J', 'Harbison, Carole E', 'Bauman, Beverley E', 'Whittaker, Gary R']",Virol J,,,True
38771dc09043758e9f76b1c8746495874d2a41bc,PMC,Different rates of (non-)synonymous mutations in astrovirus genes; correlation with gene function,http://dx.doi.org/10.1186/1743-422X-4-25,PMC1828050,17343744,CC BY,"BACKGROUND: Complete genome sequences of the Astroviridae include human, non-human mammalian and avian species. A consensus topology of astroviruses has been derived from nucleotide substitutions in the full-length genomes and from non-synonymous nucleotide substitutions in each of the three ORFs. Analyses of synonymous substitutions displayed a loss of tree structure, suggesting either saturation of the substitution model or a deviant pattern of synonymous substitutions in certain virus species. RESULTS: We analyzed the complete Astroviridae family for the inference of adaptive molecular evolution at sites and in branches. High rates of synonymous mutations are observed among the non-human virus species. Deviant patterns of synonymous substitutions are found in the capsid structural genes. Purifying selection is a dominant force among all astrovirus genes and only few codon sites showed values for the dN/dS ratio that may indicate site-specific molecular adaptation during virus evolution. One of these sites is the glycine residue of a RGD motif in ORF2 of human astrovirus serotype 1. RGD or similar integrin recognition motifs are present in nearly all astrovirus species. CONCLUSION: Phylogenetic analysis directed by maximum likelihood approximation allows the inclusion of significantly more evolutionary history and thereby, improves the estimation of dN and dS. Sites with enhanced values for dN/dS are prominent at domains in charge of environmental communication (f.i. VP27 and domain 4 in ORF1a) more than at domains dedicated to intrinsic virus functions (f.i. VP34 and ORF1b (the virus polymerase)). Integrin recognition may play a key role in astrovirus to target cell attachment.",2007 Mar 7,"['van Hemert, Formijn J', 'Lukashov, Vladimir V', 'Berkhout, Ben']",Virol J,,,True
d882f79283751d6c7f2e48cb991ee8abbcd913ae,PMC,The Transmissibility of Highly Pathogenic Avian Influenza in Commercial Poultry in Industrialised Countries,http://dx.doi.org/10.1371/journal.pone.0000349,PMC1831494,17406673,CC BY,"BACKGROUND: With the increased occurrence of outbreaks of H5N1 worldwide there is concern that the virus could enter commercial poultry farms with severe economic consequences. METHODOLOGY/PRINCIPAL FINDINGS: We analyse data from four recent outbreaks of highly pathogenic avian influenza (HPAI) in commercial poultry to estimate the farm-to-farm reproductive number for HPAI. The reproductive number is a key measure of the transmissibility of HPAI at the farm level because it can be used to evaluate the effectiveness of the control measures. In these outbreaks the mean farm-to-farm reproductive number prior to controls ranged from 1.1 to 2.4, with the maximum farm-based reproductive number in the range 2.2 to 3.2. Enhanced bio-security, movement restrictions and prompt isolation of the infected farms in all four outbreaks substantially reduced the reproductive number, but it remained close to the threshold value 1 necessary to ensure the disease will be eradicated. CONCLUSIONS/SIGNIFICANCE: Our results show that depending on the particular situation in which an outbreak of avian influenza occurs, current controls might not be enough to eradicate the disease, and therefore a close monitoring of the outbreak is required. The method we used for estimating the reproductive number is straightforward to implement and can be used in real-time. It therefore can be a useful tool to inform policy decisions.",2007 Apr 4,"['Garske, Tini', 'Clarke, Paul', 'Ghani, Azra C.']",PLoS One,,,True
78942768be77bf181f97de25fb67e8582d884e51,PMC,The Transmissibility of Highly Pathogenic Avian Influenza in Commercial Poultry in Industrialised Countries,http://dx.doi.org/10.1371/journal.pone.0000349,PMC1831494,17406673,CC BY,"BACKGROUND: With the increased occurrence of outbreaks of H5N1 worldwide there is concern that the virus could enter commercial poultry farms with severe economic consequences. METHODOLOGY/PRINCIPAL FINDINGS: We analyse data from four recent outbreaks of highly pathogenic avian influenza (HPAI) in commercial poultry to estimate the farm-to-farm reproductive number for HPAI. The reproductive number is a key measure of the transmissibility of HPAI at the farm level because it can be used to evaluate the effectiveness of the control measures. In these outbreaks the mean farm-to-farm reproductive number prior to controls ranged from 1.1 to 2.4, with the maximum farm-based reproductive number in the range 2.2 to 3.2. Enhanced bio-security, movement restrictions and prompt isolation of the infected farms in all four outbreaks substantially reduced the reproductive number, but it remained close to the threshold value 1 necessary to ensure the disease will be eradicated. CONCLUSIONS/SIGNIFICANCE: Our results show that depending on the particular situation in which an outbreak of avian influenza occurs, current controls might not be enough to eradicate the disease, and therefore a close monitoring of the outbreak is required. The method we used for estimating the reproductive number is straightforward to implement and can be used in real-time. It therefore can be a useful tool to inform policy decisions.",2007 Apr 4,"['Garske, Tini', 'Clarke, Paul', 'Ghani, Azra C.']",PLoS One,,,False
8b4eff9d625d8aa4d5795f4b07a9df388d2acfab,PMC,"Ethnoveterinary medicines used for ruminants in British Columbia, Canada",http://dx.doi.org/10.1186/1746-4269-3-11,PMC1831764,17324258,CC BY,"BACKGROUND: The use of medicinal plants is an option for livestock farmers who are not allowed to use allopathic drugs under certified organic programs or cannot afford to use allopathic drugs for minor health problems of livestock. METHODS: In 2003 we conducted semi-structured interviews with 60 participants obtained using a purposive sample. Medicinal plants are used to treat a range of conditions. A draft manual prepared from the data was then evaluated by participants at a participatory workshop. RESULTS: There are 128 plants used for ruminant health and diets, representing several plant families. The following plants are used for abscesses: Berberis aquifolium/Mahonia aquifolium Echinacea purpurea, Symphytum officinale, Bovista pila, Bovista plumbea, Achillea millefolium and Usnea longissima. Curcuma longa L., Salix scouleriana and Salix lucida are used for caprine arthritis and caprine arthritis encephalitis.Euphrasia officinalis and Matricaria chamomilla are used for eye problems. Wounds and injuries are treated with Bovista spp., Usnea longissima, Calendula officinalis, Arnica sp., Malva sp., Prunella vulgaris, Echinacea purpurea, Berberis aquifolium/Mahonia aquifolium, Achillea millefolium, Capsella bursa-pastoris, Hypericum perforatum, Lavandula officinalis, Symphytum officinale and Curcuma longa. Syzygium aromaticum and Pseudotsuga menziesii are used for coccidiosis. The following plants are used for diarrhea and scours: Plantago major, Calendula officinalis, Urtica dioica, Symphytum officinale, Pinus ponderosa, Potentilla pacifica, Althaea officinalis, Anethum graveolens, Salix alba and Ulmus fulva. Mastitis is treated with Achillea millefolium, Arctium lappa, Salix alba, Teucrium scorodonia and Galium aparine. Anethum graveolens and Rubus sp., are given for increased milk production.Taraxacum officinale, Zea mays, and Symphytum officinale are used for udder edema. Ketosis is treated with Gaultheria shallon, Vaccinium sp., and Symphytum officinale. Hedera helix and Alchemilla vulgaris are fed for retained placenta. CONCLUSION: Some of the plants showing high levels of validity were Hedera helix for retained placenta and Euphrasia officinalis for eye problems. Plants with high validity for wounds and injuries included Hypericum perforatum, Malva parviflora and Prunella vulgaris. Treatments with high validity against endoparasites included those with Juniperus communis and Pinus ponderosa. Anxiety and pain are well treated with Melissa officinalis and Nepeta caesarea.",2007 Feb 26,"['Lans, Cheryl', 'Turner, Nancy', 'Khan, Tonya', 'Brauer, Gerhard', 'Boepple, Willi']",J Ethnobiol Ethnomed,,,True
f3f471d10a36a7a28e9050c10bd4dfd680cba17b,PMC,The influenza pandemic preparedness planning tool InfluSim,http://dx.doi.org/10.1186/1471-2334-7-17,PMC1832202,17355639,CC BY,"BACKGROUND: Planning public health responses against pandemic influenza relies on predictive models by which the impact of different intervention strategies can be evaluated. Research has to date rather focused on producing predictions for certain localities or under specific conditions, than on designing a publicly available planning tool which can be applied by public health administrations. Here, we provide such a tool which is reproducible by an explicitly formulated structure and designed to operate with an optimal combination of the competing requirements of precision, realism and generality. RESULTS: InfluSim is a deterministic compartment model based on a system of over 1,000 differential equations which extend the classic SEIR model by clinical and demographic parameters relevant for pandemic preparedness planning. It allows for producing time courses and cumulative numbers of influenza cases, outpatient visits, applied antiviral treatment doses, hospitalizations, deaths and work days lost due to sickness, all of which may be associated with economic aspects. The software is programmed in Java, operates platform independent and can be executed on regular desktop computers. CONCLUSION: InfluSim is an online available software which efficiently assists public health planners in designing optimal interventions against pandemic influenza. It can reproduce the infection dynamics of pandemic influenza like complex computer simulations while offering at the same time reproducibility, higher computational performance and better operability.",2007 Mar 13,"['Eichner, Martin', 'Schwehm, Markus', 'Duerr, Hans-Peter', 'Brockmann, Stefan O']",BMC Infect Dis,,,True
aa8471e98490ab2c5a2dabea9a4d2f66c9427bfb,PMC,Whole genome molecular phylogeny of large dsDNA viruses using composition vector method,http://dx.doi.org/10.1186/1471-2148-7-41,PMC1839080,17359548,CC BY,"BACKGROUND: One important mechanism by which large DNA viruses increase their genome size is the addition of modules acquired from other viruses, host genomes or gene duplications. Phylogenetic analysis of large DNA viruses, especially using methods based on alignment, is often difficult due to the presence of horizontal gene transfer events. The recent composition vector approach, not sensitive to such events, is applied here to reconstruct the phylogeny of 124 large DNA viruses. RESULTS: The results are mostly consistent with the biologist's systematics with only a few outliers and can also provide some information for those unclassified viruses and cladistic relationships of several families. CONCLUSION: With composition vector approach we obtained the phylogenetic tree of large DNA viruses, which not only give results comparable to biologist's systematics but also provide a new way for recovering the phylogeny of viruses.",2007 Mar 15,"['Gao, Lei', 'Qi, Ji']",BMC Evol Biol,,,True
f592542c73a8294125b53d9eeef9a61cfcd9b1a3,PMC,Conserved aspartic acid 233 and alanine 231 are not required for poliovirus polymerase function in replicons,http://dx.doi.org/10.1186/1743-422X-4-28,PMC1839082,17352827,CC BY,"Nucleic acid polymerases have similar structures and motifs. The function of an aspartic acid (conserved in all classes of nucleic acid polymerases) in motif A remains poorly understood in RNA-dependent RNA polymerases. We mutated this residue to alanine in a poliovirus replicon. The resulting mutant could still replicate, although at a reduced level. In addition, mutation A231C (also in motif A) yielded high levels of replication. Taken together these results show that poliovirus polymerase conserved residues D233 and A231 are not essential to poliovirus replicon function.",2007 Mar 12,"['Freistadt, Marion S', 'Eberle, Karen E']",Virol J,,,True
b7c8e73cf095e30552a32cea04a398331c55ab41,PMC,Anticipated and current preventive behaviors in response to an anticipated human-to-human H5N1 epidemic in the Hong Kong Chinese general population,http://dx.doi.org/10.1186/1471-2334-7-18,PMC1845150,17359545,CC BY,"BACKGROUND: The prevalence of self-reported preventive behaviors in response to an anticipated local human-to-human H5N1 transmission outbreak and factors associated with such behaviors have not been examined. METHODS: A random, anonymous, cross-sectional telephone survey of 503 Hong Kong Chinese adults. RESULTS: The public in Hong Kong is likely to adopt self-protective behaviors (e.g., wearing face mask in public venues (73.8%), increasing the frequency of handwashing (86.7%)) and behaviors that protect others (e.g., wearing face masks when experiencing influenza-like illness (ILI, 92.4%), immediately seeking medical consultation (94.2%), making declarations when crossing the border with ILI (87.1%), complying to quarantine policies (88.3%)). Multivariate analyses indicated that factors related to age, full-time employment, perceived susceptibility, perceived efficacy of preventive measures, perceived higher fatality as compared to SARS, perceived chance of a major local outbreak, and being worried about self/family members contracting the virus were significantly associated with the inclination to adopt self-protective measures. Similar analyses showed that education level, variables related to perceived efficacy, perceived major local outbreak and such were significantly associated with various behaviors directed towards protecting others. CONCLUSION: In the event of a human-to-human H5N1 outbreak, the public in Hong Kong is likely to adopt preventive measures that may help contain the spread of the virus in the community.",2007 Mar 15,"['Lau, Joseph TF', 'Kim, Jean H', 'Tsui, Hi Yi', 'Griffiths, Sian']",BMC Infect Dis,,,True
4baa61e791ff5aa90affac055aee043503472aaa,PMC,"Biodiversity, traditional medicine and public health: where do they meet?",http://dx.doi.org/10.1186/1746-4269-3-14,PMC1847427,17376227,CC BY,"Given the increased use of traditional medicines, possibilities that would ensure its successful integration into a public health framework should be explored. This paper discusses some of the links between biodiversity and traditional medicine, and addresses their implications to public health. We explore the importance of biodiversity and ecosystem services to global and human health, the risks which human impacts on ecosystems and biodiversity present to human health and welfare.",2007 Mar 21,"['Alves, Rômulo RN', 'Rosa, Ierecê ML']",J Ethnobiol Ethnomed,,,True
0094b25e2500306fadbdfb41d520f2970bb086d3,PMC,Sex- and age-dependent association of SLC11A1 polymorphisms with tuberculosis in Chinese: a case control study,http://dx.doi.org/10.1186/1471-2334-7-19,PMC1847518,17371589,CC BY,"BACKGROUND: Host genetic factors are important determinants in tuberculosis (TB). The SLC11A1 (or NRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship between SLC11A1 polymorphisms and TB. METHODS: A case-control study was conducted. In total, 278 pulmonary TB patients and 282 sex- and age-matched controls without TB were recruited. All subjects were ethnic Chinese. On the basis of linkage disequilibrium pattern, three genetic markers from SLC11A1 and one from the nearby IL8RB locus were selected and examined for association with TB susceptibility. These markers were genotyped using single strand conformation polymorphism analysis or fragment analysis of amplified products. RESULTS: Statistically significant differences in allele (P = 0.0165, OR = 1.51) and genotype (P = 0.0163, OR = 1.59) frequencies of the linked markers SLC6a/b (classically called D543N and 3'UTR) of the SLC11A1 locus were found between patients and controls. With stratification by sex, positive associations were identified in the female group for both allele (P = 0.0049, OR = 2.54) and genotype (P = 0.0075, OR = 2.74) frequencies. With stratification by age, positive associations were demonstrated in the young age group (age ≤65 years) for both allele (P = 0.0047, OR = 2.52) and genotype (P = 0.0031, OR = 2.92) frequencies. All positive findings remained significant even after correction for multiple comparisons. No significant differences were noted in either the male group or the older age group. No significant differences were found for the other markers (one SLC11A1 marker and one IL8RB marker) either. CONCLUSION: This study confirmed the association between SLC11A1 and TB susceptibility and demonstrated for the first time that the association was restricted to females and the young age group.",2007 Mar 19,"['Leung, Kim Hung', 'Yip, Shea Ping', 'Wong, Wa Sang', 'Yiu, Lap San', 'Chan, Kam Keung', 'Lai, Wai Man', 'Chow, Eudora YD', 'Lin, Che Kit', 'Yam, Wing Cheong', 'Chan, Kin Sang']",BMC Infect Dis,,,True
305cf1019ca9c81126b2e527fedf79969c2c522f,PMC,"ElaD, a Deubiquitinating Protease Expressed by E. coli",http://dx.doi.org/10.1371/journal.pone.0000381,PMC1847702,17440617,CC BY,"BACKGROUND: Ubiquitin and ubiquitin-like proteins (Ubl) are designed to modify polypeptides in eukaryotes. Covalent binding of ubiquitin or Ubls to substrate proteins can be reversed by specific hydrolases. One particular set of cysteine proteases, the CE clan, which targets ubiquitin and Ubls, has homologs in eukaryotes, prokaryotes, and viruses. FINDINGS: We have cloned and analyzed the E. coli protein elaD, which is distantly related to eukaryotic CE clan members of the ULP/SENP protease family that are specific for SUMO and Nedd8. Previously misannotated as a putative sulfatase/phosphatase, elaD is an efficient and specific deubiquitinating enzyme in vitro. Interestingly, elaD is present in all intestinal pathogenic E. coli strains, but conspicuously absent from extraintestinal pathogenic strains (ExPECs). Further homologs of this protease can be found in Acanthamoeba Polyphaga Mimivirus, and in Alpha-, Beta-and Gammaproteobacteria. CONCLUSION: The expression of ULP/SENP-related hydrolases in bacteria therefore extends to plant pathogens and medically relevant strains of Escherichia coli, Legionella pneumophila, Rickettsiae, Chlamydiae, and Salmonellae, in which the elaD ortholog sseL has recently been identified as a virulence factor with deubiquitinating activity. As a counterpoint, our phylogenetic and functional examination reveals that ancient eukaryotic ULP/SENP proteases also have the potential of ubiquitin-specific hydrolysis, suggesting an early common origin of this peptidase clan.",2007 Apr 18,"['Catic, André', 'Misaghi, Shahram', 'Korbel, Gregory A.', 'Ploegh, Hidde L.']",PLoS One,,,True
71f2f3ffaa761b9d7e50b3d22eb0aacb78728bd9,PMC,Using patient-collected clinical samples and sera to detect and quantify the severe acute respiratory syndrome coronavirus (SARS-CoV),http://dx.doi.org/10.1186/1743-422X-4-32,PMC1851004,17386116,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS) caused a large outbreak of pneumonia in Beijing, China, in 2003. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect and quantify SARS-CoV in 934 sera and self-collected throat washes and fecal samples from 271 patients with laboratory-confirmed SARS managed at a single institution. RESULTS: SARS-CoV detection rates in sera were highest in the first 9 days of illness, whereas detection was highest in throat washes 5–14 days after onset of symptoms. The highest SARS-CoV RT-PCR rates (70.4–86.3%) and viral loads (log(10 )4.5–6.1) were seen in fecal samples collected 2–4 weeks after the onset of clinical illness. Fecal samples were frequently SARS-CoV RT-PCR positive beyond 40 days, and occasional sera still had SARS-CoV detected after 3 weeks of illness. CONCLUSION: In the context of an extensive outbreak with major pressure on hospital resources, patient self-collected samples are an alternative to nasopharyngeal aspirates for laboratory confirmation of SARS-CoV infection.",2007 Mar 27,"['He, Zhongping', 'Zhuang, Hui', 'Zhao, Chunhui', 'Dong, Qingming', 'Peng, Guoai', 'Dwyer, Dominic E']",Virol J,,,True
ee8dca216514deeed4c9415bc2ad8a78dc3d9670,PMC,A focus reduction neutralization assay for hepatitis C virus neutralizing antibodies,http://dx.doi.org/10.1186/1743-422X-4-35,PMC1852297,17397531,CC BY,"BACKGROUND/AIM: The role of humoral immunity in hepatitis C virus (HCV) infection is poorly understood. Nevertheless, there is increasing interest in characterizing the neutralizing antibodies in the serum of HCV-infected patients. Focus reduction assays have been widely used to evaluate neutralizing antibody responses against a range of non-cytopathic viruses. Based on the recent development of a HCV cell culture system using the genotype 2 JFH-1-strain, we developed a focus reduction assay for HCV-neutralizing antibodies. METHODS: The focus reduction assay was based on a standard microneutralization assay in which immunostained foci on tissue culture plates are counted. The neutralizing anti-HCV antibodies titers of purified serum immunoglobulin samples from seventy-seven individuals were determined using a 50% focus reduction neutralization assay. Each titer was determined as the log value of the reciprocal antibody dilution that reduced the number of viral foci by 50%. IgG antibodies were first purified from each serum in order to avoid the facilitating effect of HDL on HCV entry. RESULTS: The assay's cut-off using an ELISA and RNA HCV-negative samples was found to be 1.25 log, corresponding to a dilution of 1:18. The assay was compared with a commercial HCV ELISA and exhibited specificity and sensitivity values of 100% and 96.5%, respectively, and good reproducibility (with intra-assay and inter-assay coefficients of variation of 6.7% and 12.6%, respectively). The assay did not show any cross-reactivity with anti-HIV, anti-HBs or heterophile antibody-positive samples. The neutralizing antibodies titers were 2.13 log (1:134) for homologous samples from HCV genotype 2 infected patients harboring the same genotype as JFH-1 and 1.93 log (1:85) for heterologous samples from patients infected by genotypes other than type 2. These results confirm the presence of broadly cross-neutralizing antibodies already reported using the HCV pseudoparticles system. CONCLUSION: This study presents a simple, specific and reproducible cell culture-based assay for determination of HCV-neutralizing antibodies in human sera. The assay should be an important tool for gauging the relationship between the neutralizing antibodies response and viral load kinetics in acutely or chronically infected patients and for investigating the possible eradication or prevention of HCV infection by neutralizing antibodies.",2007 Mar 30,"['Fournier, Carole', 'Duverlie, Gilles', 'François, Catherine', 'Schnuriger, Aurelie', 'Dedeurwaerder, Sarah', 'Brochot, Etienne', 'Capron, Dominique', 'Wychowski, Czeslaw', 'Thibault, Vincent', 'Castelain, Sandrine']",Virol J,,,True
58f68e82f134cf3549778fca86251ee61975b596,PMC,High level expression of soluble glycoproteins in the allantoic fluid of embryonated chicken eggs using a Sendai virus minigenome system,http://dx.doi.org/10.1186/1472-6750-7-17,PMC1852797,17411439,CC BY,"BACKGROUND: Embryonated chicken eggs have been used since the mid-20th century to grow a wide range of animal viruses to high titers. However, eggs have found so far only limited use in the production of recombinant proteins. We now describe a system, based on a Sendai virus minigenome, to produce large amounts of heterologous viral glycoproteins in the allantoic cavity of embryonated eggs. RESULTS: Soluble forms of human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) fusion (F) proteins, devoid of their transmembrane and cytoplasmic domains, were produced in allantoic fluids using the Sendai minigenome system. The first step was rescuing in cell cultures Sendai virus minigenomes encoding the proteins of interest, with the help of wild type Sendai virus. The second step was propagating such recombinant defective viruses, together with the helper virus, in the allantoic cavity of chicken embryonated eggs, and passage to optimize protein production. When compared with the production of the same proteins in the culture supernatant of cells infected with vaccinia recombinants, the yield in the allantoic fluid was 5–10 fold higher. Mutant forms of these soluble proteins were easily constructed by site-directed mutagenesis and expressed in eggs using the same approach. CONCLUSION: The simplicity and economy of the Sendai minigenome system, together with the high yield achieved in the allantoic fluid of eggs, makes it an attractive method to express soluble glycoproteins aimed for structural studies.",2007 Apr 5,"['Corral, Teresa', 'Ver, Lorena S', 'Mottet, Geneviève', 'Cano, Olga', 'García-Barreno, Blanca', 'Calder, Lesley J', 'Skehel, John J', 'Roux, Laurent', 'Melero, José A']",BMC Biotechnol,,,True
4e0851aa892c56090edbc47e9506313d2a1b20e0,PMC,Incorporating indel information into phylogeny estimation for rapidly emerging pathogens,http://dx.doi.org/10.1186/1471-2148-7-40,PMC1853084,17359539,CC BY,"BACKGROUND: Phylogenies of rapidly evolving pathogens can be difficult to resolve because of the small number of substitutions that accumulate in the short times since divergence. To improve resolution of such phylogenies we propose using insertion and deletion (indel) information in addition to substitution information. We accomplish this through joint estimation of alignment and phylogeny in a Bayesian framework, drawing inference using Markov chain Monte Carlo. Joint estimation of alignment and phylogeny sidesteps biases that stem from conditioning on a single alignment by taking into account the ensemble of near-optimal alignments. RESULTS: We introduce a novel Markov chain transition kernel that improves computational efficiency by proposing non-local topology rearrangements and by block sampling alignment and topology parameters. In addition, we extend our previous indel model to increase biological realism by placing indels preferentially on longer branches. We demonstrate the ability of indel information to increase phylogenetic resolution in examples drawn from within-host viral sequence samples. We also demonstrate the importance of taking alignment uncertainty into account when using such information. Finally, we show that codon-based substitution models can significantly affect alignment quality and phylogenetic inference by unrealistically forcing indels to begin and end between codons. CONCLUSION: These results indicate that indel information can improve phylogenetic resolution of recently diverged pathogens and that alignment uncertainty should be considered in such analyses.",2007 Mar 14,"['Redelings, Benjamin D', 'Suchard, Marc A']",BMC Evol Biol,,,True
0fcfac3230a7ab2f3b600fd06eebdf084066d01b,PMC,"Application of Broad-Spectrum, Sequence-Based Pathogen Identification in an Urban Population",http://dx.doi.org/10.1371/journal.pone.0000419,PMC1855431,17502915,CC0,"A broad spectrum detection platform that provides sequence level resolution of target regions would have a significant impact in public health, case management, and means of expanding our understanding of the etiology of diseases. A previously developed respiratory pathogen microarray (RPM v.1) demonstrated the capability of this platform for this purpose. This newly developed RPM v.1 was used to analyze 424 well-characterized nasal wash specimens from patients presenting with febrile respiratory illness in the Washington, D. C. metropolitan region. For each specimen, the RPM v.1 results were compared against composite reference assay (viral and bacterial culture and, where appropriate, RT-PCR/PCR) results. Across this panel, the RPM assay showed ≥98% overall agreement for all the organisms detected compared with reference methods. Additionally, the RPM v.1 results provide sequence information which allowed phylogenetic classification of circulating influenza A viruses in ∼250 clinical specimens, and allowed monitoring the genetic variation as well as antigenic variability prediction. Multiple pathogens (2–4) were detected in 58 specimens (13.7%) with notably increased abundances of respiratory colonizers (esp. S. pneumoniae) during viral infection. This first-ever comparison of a broad-spectrum viral and bacterial identification technology of this type against a large battery of conventional “gold standard” assays confirms the utility of the approach for both medical surveillance and investigations of complex etiologies of illness caused by respiratory co-infections.",2007 May 9,"['Lin, Baochuan', 'Malanoski, Anthony P.', 'Wang, Zheng', 'Blaney, Kate M.', 'Ligler, Adam G.', 'Rowley, Robb K.', 'Hanson, Eric H.', 'von Rosenvinge, Erik', 'Ligler, Frances S.', 'Kusterbeck, Anne W.', 'Metzgar, David', 'Barrozo, Christopher P.', 'Russell, Kevin L.', 'Tibbetts, Clark', 'Schnur, Joel M.', 'Stenger, David A.']",PLoS One,,,True
dc7809e3cbcc5bb53b481641f6796891f4ecedc4,PMC,Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.ppat.0030064,PMC1864993,17480120,CC BY,"We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus–specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.",2007 May 4,"['Gaynor, Anne M', 'Nissen, Michael D', 'Whiley, David M', 'Mackay, Ian M', 'Lambert, Stephen B', 'Wu, Guang', 'Brennan, Daniel C', 'Storch, Gregory A', 'Sloots, Theo P', 'Wang, David']",PLoS Pathog,,,True
f12d8e834fd7275d5c656309ff0ac1e2343c68dd,PMC,Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.ppat.0030064,PMC1864993,17480120,CC BY,"We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus–specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.",2007 May 4,"['Gaynor, Anne M', 'Nissen, Michael D', 'Whiley, David M', 'Mackay, Ian M', 'Lambert, Stephen B', 'Wu, Guang', 'Brennan, Daniel C', 'Storch, Gregory A', 'Sloots, Theo P', 'Wang, David']",PLoS Pathog,,,False
654bfa151888fd9914a4f78a4980c01b3817c9a4,PMC,Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.ppat.0030064,PMC1864993,17480120,CC BY,"We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus–specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.",2007 May 4,"['Gaynor, Anne M', 'Nissen, Michael D', 'Whiley, David M', 'Mackay, Ian M', 'Lambert, Stephen B', 'Wu, Guang', 'Brennan, Daniel C', 'Storch, Gregory A', 'Sloots, Theo P', 'Wang, David']",PLoS Pathog,,,False
4c01a2cce1c31f2f194ea63d3639282f96984c8a,PMC,Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.ppat.0030064,PMC1864993,17480120,CC BY,"We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus–specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.",2007 May 4,"['Gaynor, Anne M', 'Nissen, Michael D', 'Whiley, David M', 'Mackay, Ian M', 'Lambert, Stephen B', 'Wu, Guang', 'Brennan, Daniel C', 'Storch, Gregory A', 'Sloots, Theo P', 'Wang, David']",PLoS Pathog,,,False
b199920959658ae175110d31a052db162aaf3d02,PMC,Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.ppat.0030064,PMC1864993,17480120,CC BY,"We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus–specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.",2007 May 4,"['Gaynor, Anne M', 'Nissen, Michael D', 'Whiley, David M', 'Mackay, Ian M', 'Lambert, Stephen B', 'Wu, Guang', 'Brennan, Daniel C', 'Storch, Gregory A', 'Sloots, Theo P', 'Wang, David']",PLoS Pathog,,,False
b3f43bc854e6c08a8ce20030be933fe9d08afc41,PMC,Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.ppat.0030064,PMC1864993,17480120,CC BY,"We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus–specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.",2007 May 4,"['Gaynor, Anne M', 'Nissen, Michael D', 'Whiley, David M', 'Mackay, Ian M', 'Lambert, Stephen B', 'Wu, Guang', 'Brennan, Daniel C', 'Storch, Gregory A', 'Sloots, Theo P', 'Wang, David']",PLoS Pathog,,,False
8b9c29263c0ecc9a29e8f5ee2a4afa9b95e1a6c9,PMC,Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.ppat.0030064,PMC1864993,17480120,CC BY,"We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus–specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.",2007 May 4,"['Gaynor, Anne M', 'Nissen, Michael D', 'Whiley, David M', 'Mackay, Ian M', 'Lambert, Stephen B', 'Wu, Guang', 'Brennan, Daniel C', 'Storch, Gregory A', 'Sloots, Theo P', 'Wang, David']",PLoS Pathog,,,False
6f08b893f2190ac79dbeb85302703bf519037b7b,PMC,"Fellowships, Grants, & Awards",,PMC1867954,,CC0,,2007 May,,Environ Health Perspect,,,True
60081af7cc91d270d05e6cb45285578f86c918fb,PMC,Analysis of Intraviral Protein-Protein Interactions of the SARS Coronavirus ORFeome,http://dx.doi.org/10.1371/journal.pone.0000459,PMC1868897,17520018,CC BY,"The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted to encode 14 functional open reading frames, leading to the expression of up to 30 structural and non-structural protein products. The functions of a large number of viral ORFs are poorly understood or unknown. In order to gain more insight into functions and modes of action and interaction of the different proteins, we cloned the viral ORFeome and performed a genome-wide analysis for intraviral protein interactions and for intracellular localization. 900 pairwise interactions were tested by yeast-two-hybrid matrix analysis, and more than 65 positive non-redundant interactions, including six self interactions, were identified. About 38% of interactions were subsequently confirmed by CoIP in mammalian cells. Nsp2, nsp8 and ORF9b showed a wide range of interactions with other viral proteins. Nsp8 interacts with replicase proteins nsp2, nsp5, nsp6, nsp7, nsp8, nsp9, nsp12, nsp13 and nsp14, indicating a crucial role as a major player within the replication complex machinery. It was shown by others that nsp8 is essential for viral replication in vitro, whereas nsp2 is not. We show that also accessory protein ORF9b does not play a pivotal role for viral replication, as it can be deleted from the virus displaying normal plaque sizes and growth characteristics in Vero cells. However, it can be expected to be important for the virus-host interplay and for pathogenicity, due to its large number of interactions, by enhancing the global stability of the SARS proteome network, or play some unrealized role in regulating protein-protein interactions. The interactions identified provide valuable material for future studies.",2007 May 23,"['von Brunn, Albrecht', 'Teepe, Carola', 'Simpson, Jeremy C.', 'Pepperkok, Rainer', 'Friedel, Caroline C.', 'Zimmer, Ralf', 'Roberts, Rhonda', 'Baric, Ralph', 'Haas, Jürgen']",PLoS One,,,True
435baf47b4f78fc06a8376f451993059407d2972,PMC,Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry,http://dx.doi.org/10.1371/journal.pone.0000489,PMC1876795,17534439,CC0,"BACKGROUND: Effective influenza surveillance requires new methods capable of rapid and inexpensive genomic analysis of evolving viral species for pandemic preparedness, to understand the evolution of circulating viral species, and for vaccine strain selection. We have developed one such approach based on previously described broad-range reverse transcription PCR/electrospray ionization mass spectrometry (RT-PCR/ESI-MS) technology. METHODS AND PRINCIPAL FINDINGS: Analysis of base compositions of RT-PCR amplicons from influenza core gene segments (PB1, PB2, PA, M, NS, NP) are used to provide sub-species identification and infer influenza virus H and N subtypes. Using this approach, we detected and correctly identified 92 mammalian and avian influenza isolates, representing 30 different H and N types, including 29 avian H5N1 isolates. Further, direct analysis of 656 human clinical respiratory specimens collected over a seven-year period (1999–2006) showed correct identification of the viral species and subtypes with >97% sensitivity and specificity. Base composition derived clusters inferred from this analysis showed 100% concordance to previously established clades. Ongoing surveillance of samples from the recent influenza virus seasons (2005–2006) showed evidence for emergence and establishment of new genotypes of circulating H3N2 strains worldwide. Mixed viral quasispecies were found in approximately 1% of these recent samples providing a view into viral evolution. CONCLUSION/SIGNIFICANCE: Thus, rapid RT-PCR/ESI-MS analysis can be used to simultaneously identify all species of influenza viruses with clade-level resolution, identify mixed viral populations and monitor global spread and emergence of novel viral genotypes. This high-throughput method promises to become an integral component of influenza surveillance.",2007 May 30,"['Sampath, Rangarajan', 'Russell, Kevin L.', 'Massire, Christian', 'Eshoo, Mark W.', 'Harpin, Vanessa', 'Blyn, Lawrence B.', 'Melton, Rachael', 'Ivy, Cristina', 'Pennella, Thuy', 'Li, Feng', 'Levene, Harold', 'Hall, Thomas A.', 'Libby, Brian', 'Fan, Nancy', 'Walcott, Demetrius J.', 'Ranken, Raymond', 'Pear, Michael', 'Schink, Amy', 'Gutierrez, Jose', 'Drader, Jared', 'Moore, David', 'Metzgar, David', 'Addington, Lynda', 'Rothman, Richard', 'Gaydos, Charlotte A.', 'Yang, Samuel', 'St. George, Kirsten', 'Fuschino, Meghan E.', 'Dean, Amy B.', 'Stallknecht, David E.', 'Goekjian, Ginger', 'Yingst, Samuel', 'Monteville, Marshall', 'Saad, Magdi D.', 'Whitehouse, Chris A.', 'Baldwin, Carson', 'Rudnick, Karl H.', 'Hofstadler, Steven A.', 'Lemon, Stanley M.', 'Ecker, David J.']",PLoS One,,,True
3c0ab78f942980f89e0c14faf2b393328b79f27d,PMC,Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry,http://dx.doi.org/10.1371/journal.pone.0000489,PMC1876795,17534439,CC0,"BACKGROUND: Effective influenza surveillance requires new methods capable of rapid and inexpensive genomic analysis of evolving viral species for pandemic preparedness, to understand the evolution of circulating viral species, and for vaccine strain selection. We have developed one such approach based on previously described broad-range reverse transcription PCR/electrospray ionization mass spectrometry (RT-PCR/ESI-MS) technology. METHODS AND PRINCIPAL FINDINGS: Analysis of base compositions of RT-PCR amplicons from influenza core gene segments (PB1, PB2, PA, M, NS, NP) are used to provide sub-species identification and infer influenza virus H and N subtypes. Using this approach, we detected and correctly identified 92 mammalian and avian influenza isolates, representing 30 different H and N types, including 29 avian H5N1 isolates. Further, direct analysis of 656 human clinical respiratory specimens collected over a seven-year period (1999–2006) showed correct identification of the viral species and subtypes with >97% sensitivity and specificity. Base composition derived clusters inferred from this analysis showed 100% concordance to previously established clades. Ongoing surveillance of samples from the recent influenza virus seasons (2005–2006) showed evidence for emergence and establishment of new genotypes of circulating H3N2 strains worldwide. Mixed viral quasispecies were found in approximately 1% of these recent samples providing a view into viral evolution. CONCLUSION/SIGNIFICANCE: Thus, rapid RT-PCR/ESI-MS analysis can be used to simultaneously identify all species of influenza viruses with clade-level resolution, identify mixed viral populations and monitor global spread and emergence of novel viral genotypes. This high-throughput method promises to become an integral component of influenza surveillance.",2007 May 30,"['Sampath, Rangarajan', 'Russell, Kevin L.', 'Massire, Christian', 'Eshoo, Mark W.', 'Harpin, Vanessa', 'Blyn, Lawrence B.', 'Melton, Rachael', 'Ivy, Cristina', 'Pennella, Thuy', 'Li, Feng', 'Levene, Harold', 'Hall, Thomas A.', 'Libby, Brian', 'Fan, Nancy', 'Walcott, Demetrius J.', 'Ranken, Raymond', 'Pear, Michael', 'Schink, Amy', 'Gutierrez, Jose', 'Drader, Jared', 'Moore, David', 'Metzgar, David', 'Addington, Lynda', 'Rothman, Richard', 'Gaydos, Charlotte A.', 'Yang, Samuel', 'St. George, Kirsten', 'Fuschino, Meghan E.', 'Dean, Amy B.', 'Stallknecht, David E.', 'Goekjian, Ginger', 'Yingst, Samuel', 'Monteville, Marshall', 'Saad, Magdi D.', 'Whitehouse, Chris A.', 'Baldwin, Carson', 'Rudnick, Karl H.', 'Hofstadler, Steven A.', 'Lemon, Stanley M.', 'Ecker, David J.']",PLoS One,,,False
67f0d4bc3ea5b8ae8ae677ecde74ab21c7ad740b,PMC,Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry,http://dx.doi.org/10.1371/journal.pone.0000489,PMC1876795,17534439,CC0,"BACKGROUND: Effective influenza surveillance requires new methods capable of rapid and inexpensive genomic analysis of evolving viral species for pandemic preparedness, to understand the evolution of circulating viral species, and for vaccine strain selection. We have developed one such approach based on previously described broad-range reverse transcription PCR/electrospray ionization mass spectrometry (RT-PCR/ESI-MS) technology. METHODS AND PRINCIPAL FINDINGS: Analysis of base compositions of RT-PCR amplicons from influenza core gene segments (PB1, PB2, PA, M, NS, NP) are used to provide sub-species identification and infer influenza virus H and N subtypes. Using this approach, we detected and correctly identified 92 mammalian and avian influenza isolates, representing 30 different H and N types, including 29 avian H5N1 isolates. Further, direct analysis of 656 human clinical respiratory specimens collected over a seven-year period (1999–2006) showed correct identification of the viral species and subtypes with >97% sensitivity and specificity. Base composition derived clusters inferred from this analysis showed 100% concordance to previously established clades. Ongoing surveillance of samples from the recent influenza virus seasons (2005–2006) showed evidence for emergence and establishment of new genotypes of circulating H3N2 strains worldwide. Mixed viral quasispecies were found in approximately 1% of these recent samples providing a view into viral evolution. CONCLUSION/SIGNIFICANCE: Thus, rapid RT-PCR/ESI-MS analysis can be used to simultaneously identify all species of influenza viruses with clade-level resolution, identify mixed viral populations and monitor global spread and emergence of novel viral genotypes. This high-throughput method promises to become an integral component of influenza surveillance.",2007 May 30,"['Sampath, Rangarajan', 'Russell, Kevin L.', 'Massire, Christian', 'Eshoo, Mark W.', 'Harpin, Vanessa', 'Blyn, Lawrence B.', 'Melton, Rachael', 'Ivy, Cristina', 'Pennella, Thuy', 'Li, Feng', 'Levene, Harold', 'Hall, Thomas A.', 'Libby, Brian', 'Fan, Nancy', 'Walcott, Demetrius J.', 'Ranken, Raymond', 'Pear, Michael', 'Schink, Amy', 'Gutierrez, Jose', 'Drader, Jared', 'Moore, David', 'Metzgar, David', 'Addington, Lynda', 'Rothman, Richard', 'Gaydos, Charlotte A.', 'Yang, Samuel', 'St. George, Kirsten', 'Fuschino, Meghan E.', 'Dean, Amy B.', 'Stallknecht, David E.', 'Goekjian, Ginger', 'Yingst, Samuel', 'Monteville, Marshall', 'Saad, Magdi D.', 'Whitehouse, Chris A.', 'Baldwin, Carson', 'Rudnick, Karl H.', 'Hofstadler, Steven A.', 'Lemon, Stanley M.', 'Ecker, David J.']",PLoS One,,,False
93549e874bd97796034c7f22ad3095af3b8d8d7e,PMC,Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry,http://dx.doi.org/10.1371/journal.pone.0000489,PMC1876795,17534439,CC0,"BACKGROUND: Effective influenza surveillance requires new methods capable of rapid and inexpensive genomic analysis of evolving viral species for pandemic preparedness, to understand the evolution of circulating viral species, and for vaccine strain selection. We have developed one such approach based on previously described broad-range reverse transcription PCR/electrospray ionization mass spectrometry (RT-PCR/ESI-MS) technology. METHODS AND PRINCIPAL FINDINGS: Analysis of base compositions of RT-PCR amplicons from influenza core gene segments (PB1, PB2, PA, M, NS, NP) are used to provide sub-species identification and infer influenza virus H and N subtypes. Using this approach, we detected and correctly identified 92 mammalian and avian influenza isolates, representing 30 different H and N types, including 29 avian H5N1 isolates. Further, direct analysis of 656 human clinical respiratory specimens collected over a seven-year period (1999–2006) showed correct identification of the viral species and subtypes with >97% sensitivity and specificity. Base composition derived clusters inferred from this analysis showed 100% concordance to previously established clades. Ongoing surveillance of samples from the recent influenza virus seasons (2005–2006) showed evidence for emergence and establishment of new genotypes of circulating H3N2 strains worldwide. Mixed viral quasispecies were found in approximately 1% of these recent samples providing a view into viral evolution. CONCLUSION/SIGNIFICANCE: Thus, rapid RT-PCR/ESI-MS analysis can be used to simultaneously identify all species of influenza viruses with clade-level resolution, identify mixed viral populations and monitor global spread and emergence of novel viral genotypes. This high-throughput method promises to become an integral component of influenza surveillance.",2007 May 30,"['Sampath, Rangarajan', 'Russell, Kevin L.', 'Massire, Christian', 'Eshoo, Mark W.', 'Harpin, Vanessa', 'Blyn, Lawrence B.', 'Melton, Rachael', 'Ivy, Cristina', 'Pennella, Thuy', 'Li, Feng', 'Levene, Harold', 'Hall, Thomas A.', 'Libby, Brian', 'Fan, Nancy', 'Walcott, Demetrius J.', 'Ranken, Raymond', 'Pear, Michael', 'Schink, Amy', 'Gutierrez, Jose', 'Drader, Jared', 'Moore, David', 'Metzgar, David', 'Addington, Lynda', 'Rothman, Richard', 'Gaydos, Charlotte A.', 'Yang, Samuel', 'St. George, Kirsten', 'Fuschino, Meghan E.', 'Dean, Amy B.', 'Stallknecht, David E.', 'Goekjian, Ginger', 'Yingst, Samuel', 'Monteville, Marshall', 'Saad, Magdi D.', 'Whitehouse, Chris A.', 'Baldwin, Carson', 'Rudnick, Karl H.', 'Hofstadler, Steven A.', 'Lemon, Stanley M.', 'Ecker, David J.']",PLoS One,,,False
c65f0939cf35a0f04bf93bd6e8f771b8521563a5,PMC,Transmission Parameters of the 2001 Foot and Mouth Epidemic in Great Britain,http://dx.doi.org/10.1371/journal.pone.0000502,PMC1876810,17551582,CC BY,"Despite intensive ongoing research, key aspects of the spatial-temporal evolution of the 2001 foot and mouth disease (FMD) epidemic in Great Britain (GB) remain unexplained. Here we develop a Markov Chain Monte Carlo (MCMC) method for estimating epidemiological parameters of the 2001 outbreak for a range of simple transmission models. We make the simplifying assumption that infectious farms were completely observed in 2001, equivalent to assuming that farms that were proactively culled but not diagnosed with FMD were not infectious, even if some were infected. We estimate how transmission parameters varied through time, highlighting the impact of the control measures on the progression of the epidemic. We demonstrate statistically significant evidence for assortative contact patterns between animals of the same species. Predictive risk maps of the transmission potential in different geographic areas of GB are presented for the fitted models.",2007 Jun 6,"['Chis Ster, Irina', 'Ferguson, Neil M.']",PLoS One,,,True
8275311de465e4fdbb25ebddf76302cd4603c36c,PMC,Transparent Development of the WHO Rapid Advice Guidelines,http://dx.doi.org/10.1371/journal.pmed.0040119,PMC1877972,17535099,CC0,"Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.",2007 May 29,"['Schünemann, Holger J', 'Hill, Suzanne R', 'Kakad, Meetali', 'Vist, Gunn E', 'Bellamy, Richard', 'Stockman, Lauren', 'Wisløff, Torbjørn Fosen', 'Mar, Chris Del', 'Hayden, Frederick', 'Uyeki, Timothy M', 'Farrar, Jeremy', 'Yazdanpanah, Yazdan', 'Zucker, Howard', 'Beigel, John', 'Chotpitayasunondh, Tawee', 'Hien, Tran Tinh', 'Özbay, Bülent', 'Sugaya, Norio', 'Oxman, Andrew D']",PLoS Med,,,True
849b571a103b4c39b2515f3769da04a6ff4918ae,PMC,Transparent Development of the WHO Rapid Advice Guidelines,http://dx.doi.org/10.1371/journal.pmed.0040119,PMC1877972,17535099,CC0,"Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.",2007 May 29,"['Schünemann, Holger J', 'Hill, Suzanne R', 'Kakad, Meetali', 'Vist, Gunn E', 'Bellamy, Richard', 'Stockman, Lauren', 'Wisløff, Torbjørn Fosen', 'Mar, Chris Del', 'Hayden, Frederick', 'Uyeki, Timothy M', 'Farrar, Jeremy', 'Yazdanpanah, Yazdan', 'Zucker, Howard', 'Beigel, John', 'Chotpitayasunondh, Tawee', 'Hien, Tran Tinh', 'Özbay, Bülent', 'Sugaya, Norio', 'Oxman, Andrew D']",PLoS Med,,,False
06c06c96cc93d025b70468793358918fa3c96978,PMC,Transparent Development of the WHO Rapid Advice Guidelines,http://dx.doi.org/10.1371/journal.pmed.0040119,PMC1877972,17535099,CC0,"Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.",2007 May 29,"['Schünemann, Holger J', 'Hill, Suzanne R', 'Kakad, Meetali', 'Vist, Gunn E', 'Bellamy, Richard', 'Stockman, Lauren', 'Wisløff, Torbjørn Fosen', 'Mar, Chris Del', 'Hayden, Frederick', 'Uyeki, Timothy M', 'Farrar, Jeremy', 'Yazdanpanah, Yazdan', 'Zucker, Howard', 'Beigel, John', 'Chotpitayasunondh, Tawee', 'Hien, Tran Tinh', 'Özbay, Bülent', 'Sugaya, Norio', 'Oxman, Andrew D']",PLoS Med,,,False
492da4648300bbc57c649c5558016893b1fa47d7,PMC,Transparent Development of the WHO Rapid Advice Guidelines,http://dx.doi.org/10.1371/journal.pmed.0040119,PMC1877972,17535099,CC0,"Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.",2007 May 29,"['Schünemann, Holger J', 'Hill, Suzanne R', 'Kakad, Meetali', 'Vist, Gunn E', 'Bellamy, Richard', 'Stockman, Lauren', 'Wisløff, Torbjørn Fosen', 'Mar, Chris Del', 'Hayden, Frederick', 'Uyeki, Timothy M', 'Farrar, Jeremy', 'Yazdanpanah, Yazdan', 'Zucker, Howard', 'Beigel, John', 'Chotpitayasunondh, Tawee', 'Hien, Tran Tinh', 'Özbay, Bülent', 'Sugaya, Norio', 'Oxman, Andrew D']",PLoS Med,,,False
dbe2626b505d8655d0062401ea8b901140fb1ca4,PMC,Transparent Development of the WHO Rapid Advice Guidelines,http://dx.doi.org/10.1371/journal.pmed.0040119,PMC1877972,17535099,CC0,"Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.",2007 May 29,"['Schünemann, Holger J', 'Hill, Suzanne R', 'Kakad, Meetali', 'Vist, Gunn E', 'Bellamy, Richard', 'Stockman, Lauren', 'Wisløff, Torbjørn Fosen', 'Mar, Chris Del', 'Hayden, Frederick', 'Uyeki, Timothy M', 'Farrar, Jeremy', 'Yazdanpanah, Yazdan', 'Zucker, Howard', 'Beigel, John', 'Chotpitayasunondh, Tawee', 'Hien, Tran Tinh', 'Özbay, Bülent', 'Sugaya, Norio', 'Oxman, Andrew D']",PLoS Med,,,False
bcfb37580928c801c7876dce689440d19707e18d,PMC,Transparent Development of the WHO Rapid Advice Guidelines,http://dx.doi.org/10.1371/journal.pmed.0040119,PMC1877972,17535099,CC0,"Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.",2007 May 29,"['Schünemann, Holger J', 'Hill, Suzanne R', 'Kakad, Meetali', 'Vist, Gunn E', 'Bellamy, Richard', 'Stockman, Lauren', 'Wisløff, Torbjørn Fosen', 'Mar, Chris Del', 'Hayden, Frederick', 'Uyeki, Timothy M', 'Farrar, Jeremy', 'Yazdanpanah, Yazdan', 'Zucker, Howard', 'Beigel, John', 'Chotpitayasunondh, Tawee', 'Hien, Tran Tinh', 'Özbay, Bülent', 'Sugaya, Norio', 'Oxman, Andrew D']",PLoS Med,,,False
79695b2d02cc1106f7cbf9ab80e3a53cee4b054e,PMC,Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A viruses,http://dx.doi.org/10.1186/1743-422X-4-39,PMC1878474,17477867,CC BY,"Chloroquine is a 4-aminoquinoline previously used in malaria therapy and now becoming an emerging investigational antiviral drug due to its broad spectrum of antiviral activities. To explore whether the low pH-dependency of influenza A viruses might affect the antiviral effects of chloroquine at clinically achievable concentrations, we tested the antiviral effects of this drug on selected human and avian viruses belonging to different subtypes and displaying different pH requirements. Results showed a correlation between the responses to chloroquine and NH(4)Cl, a lysosomotropic agent known to increase the pH of intracellular vesicles. Time-of-addition experiments showed that the inhibitory effect of chloroquine was maximal when the drug had been added at the time of infection and was lost after 2 h post-infection. This timing approximately corresponds to that of virus/cell fusion. Moreover, there was a clear correlation between the EC(50 )of chloroquine in vitro and the electrostatic potential of the HA subunit (HA2) mediating the virus/cell fusion process. Overall, the present study highlights the critical importance of a host cell factor such as intravesicular pH in determining the anti-influenza activity of chloroquine and other lysosomotropic agents.",2007 May 3,"['Di Trani, Livia', 'Savarino, Andrea', 'Campitelli, Laura', 'Norelli, Sandro', 'Puzelli, Simona', ""D'Ostilio, Daniela"", 'Vignolo, Edoardo', 'Donatelli, Isabella', 'Cassone, Antonio']",Virol J,,,True
e5ec3d4854fa2bfba10cae487ea5271ed00a24fa,PMC,IFNG +874T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-γ production,http://dx.doi.org/10.1186/1471-2334-7-33,PMC1878480,17456233,CC BY,"BACKGROUND: Interferon-gamma is a key cytokine in the protective responses against intracellular pathogens. A single nucleotide polymorphism (SNP) located in the first intron of the human IFN-γ gene can putatively influence the secretion of cytokine with an impact on infection outcome as demonstrated for tuberculosis and other complex diseases. Our aim was to investigate the putative association of IFNG+874T/A SNP with American tegumentary leishmaniasis (ATL) and also the influence of this SNP in the secretion of IFN-γ in vitro. METHODS: Brazilian ATL patients (78 cutaneous, CL, and 58 mucosal leishmaniasis, ML) and 609 healthy volunteers were evaluated. The genotype of +874 region in the IFN-γ gene was carried out by Amplification Refractory Mutational System (ARMS-PCR). Leishmania-induced IFN-γ production on peripheral blood mononuclear cell (PBMC) culture supernatants was assessed by ELISA. RESULTS: There are no differences between +874T/A SNP frequency in cases and controls or in ML versus CL patients. Cutaneous leishmaniasis cases exhibiting AA genotype produced lower levels of IFN-γ than TA/TT genotypes. In mucosal cases, high and low IFN-γ producers were clearly demonstrated but no differences in the cytokine production was observed among the IFNG +874T or A carriers. CONCLUSION: Our results suggest that +874T/A polymorphism was not associated with either susceptibility or severity to leishmaniasis. Despite this, IFNG +874T/A SNP could be involved in the pathogenesis of leishmaniasis by influencing the amount of cytokine released by CL patients, although it could not prevent disease development. On the other hand, it is possible that in ML cases, other potential polymorphic regulatory genes such as TNF-α and IL-10 are also involved thus interfering with IFN-γ secretion.",2007 Apr 24,"['Matos, Guilherme Inocêncio', 'Covas, Claudia de J Fernandes', 'Bittar, Rita de Cássia', 'Gomes-Silva, Adriano', 'Marques, Fabiana', 'Maniero, Viviane C', 'Amato, Valdir S', 'Oliveira-Neto, Manoel P', 'Mattos, Marise da Silva', 'Pirmez, Claude', 'Sampaio, Elizabeth P', 'Moraes, Milton O', 'Da-Cruz, Alda Maria']",BMC Infect Dis,,,True
49b957bb681c7cae440ef4241a9fc99f37028d78,PMC,Prophylactic and Therapeutic Efficacy of Human Monoclonal Antibodies against H5N1 Influenza,http://dx.doi.org/10.1371/journal.pmed.0040178,PMC1880850,17535101,CC0,"BACKGROUND: New prophylactic and therapeutic strategies to combat human infections with highly pathogenic avian influenza (HPAI) H5N1 viruses are needed. We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs) and tested their efficacy for prophylaxis and therapy in a murine model of infection. METHODS AND FINDINGS: Using Epstein-Barr virus we immortalized memory B cells from Vietnamese adults who had recovered from infections with HPAI H5N1 viruses. Supernatants from B cell lines were screened in a virus neutralization assay. B cell lines secreting neutralizing antibodies were cloned and the mAbs purified. The cross-reactivity of these antibodies for different strains of H5N1 was tested in vitro by neutralization assays, and their prophylactic and therapeutic efficacy in vivo was tested in mice. In vitro, mAbs FLA3.14 and FLD20.19 neutralized both Clade I and Clade II H5N1 viruses, whilst FLA5.10 and FLD21.140 neutralized Clade I viruses only. In vivo, FLA3.14 and FLA5.10 conferred protection from lethality in mice challenged with A/Vietnam/1203/04 (H5N1) in a dose-dependent manner. mAb prophylaxis provided a statistically significant reduction in pulmonary virus titer, reduced associated inflammation in the lungs, and restricted extrapulmonary dissemination of the virus. Therapeutic doses of FLA3.14, FLA5.10, FLD20.19, and FLD21.140 provided robust protection from lethality at least up to 72 h postinfection with A/Vietnam/1203/04 (H5N1). mAbs FLA3.14, FLD21.140 and FLD20.19, but not FLA5.10, were also therapeutically active in vivo against the Clade II virus A/Indonesia/5/2005 (H5N1). CONCLUSIONS: These studies provide proof of concept that fully human mAbs with neutralizing activity can be rapidly generated from the peripheral blood of convalescent patients and that these mAbs are effective for the prevention and treatment of H5N1 infection in a mouse model. A panel of neutralizing, cross-reactive mAbs might be useful for prophylaxis or adjunctive treatment of human cases of H5N1 influenza.",2007 May 29,"['Simmons, Cameron P', 'Bernasconi, Nadia L', 'Suguitan, Amorsolo L', 'Mills, Kimberly', 'Ward, Jerrold M', 'Chau, Nguyen Van Vinh', 'Hien, Tran Tinh', 'Sallusto, Federica', 'Ha, Do Quang', 'Farrar, Jeremy', 'de Jong, Menno D', 'Lanzavecchia, Antonio', 'Subbarao, Kanta']",PLoS Med,,,True
2871cf7a741e9af5c94009d2cf5f368932f6f47e,PMC,How Is WHO Responding to Global Public Health Threats?,http://dx.doi.org/10.1371/journal.pmed.0040197,PMC1880862,17535110,CC BY,The editors discuss two recent WHO initiatives on preparing for and responding to global public health threats: the WHO Rapid Advice Guidelines Group and the new revision of the International Health Regulations.,2007 May 29,,PLoS Med,,,True
1ff2f23a621ca476cd59ade285f8b9198ca178fd,PMC,Arthritis suppression by NADPH activation operates through an interferon-β pathway,http://dx.doi.org/10.1186/1741-7007-5-19,PMC1884140,17490473,CC BY,"BACKGROUND: A polymorphism in the activating component of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, neutrophil cytosolic factor 1 (NCF1), has previously been identified as a regulator of arthritis severity in mice and rats. This discovery resulted in a search for NADPH oxidase-activating substances as a potential new approach to treat autoimmune disorders such as rheumatoid arthritis (RA). We have recently shown that compounds inducing NCF1-dependent oxidative burst, e.g. phytol, have a strong ameliorating effect on arthritis in rats. However, the underlying molecular mechanism is still not clearly understood. The aim of this study was to use gene-expression profiling to understand the protective effect against arthritis of activation of NADPH oxidase in the immune system. RESULTS: Subcutaneous administration of phytol leads to an accumulation of the compound in the inguinal lymph nodes, with peak levels being reached approximately 10 days after administration. Hence, global gene-expression profiling on inguinal lymph nodes was performed 10 days after the induction of pristane-induced arthritis (PIA) and phytol administration. The differentially expressed genes could be divided into two pathways, consisting of genes regulated by different interferons. IFN-γ regulated the pathway associated with arthritis development, whereas IFN-β regulated the pathway associated with disease protection through phytol. Importantly, these two molecular pathways were also confirmed to differentiate between the arthritis-susceptible dark agouti (DA) rat, (with an Ncf-1(DA )allele that allows only low oxidative burst), and the arthritis-protected DA.Ncf-1(E3 )rat (with an Ncf1(E3 )allele that allows a stronger oxidative burst). CONCLUSION: Naturally occurring genetic polymorphisms in the Ncf-1 gene modulate the activity of the NADPH oxidase complex, which strongly regulates the severity of arthritis. We now show that the Ncf-1 allele that enhances oxidative burst and protects against arthritis is operating through an IFN-β-associated pathway, whereas the arthritis-driving allele operates through an IFN-γ-associated pathway. Treatment of arthritis-susceptible rats with an NADPH oxidase-activating substance, phytol, protects against arthritis. Interestingly, the treatment led to a restoration of the oxidative-burst effect and induction of a strikingly similar IFN-β-dependent pathway, as seen with the disease-protective Ncf1 polymorphism.",2007 May 9,"['Olofsson, Peter', 'Nerstedt, Annika', 'Hultqvist, Malin', 'Nilsson, Elisabeth C', 'Andersson, Sofia', 'Bergelin, Anna', 'Holmdahl, Rikard']",BMC Biol,,,True
6e2b123ad273e69afefb875594ac0fac7c785c74,PMC,Expression stability of commonly used reference genes in canine articular connective tissues,http://dx.doi.org/10.1186/1746-6148-3-7,PMC1884148,17484782,CC BY,"BACKGROUND: The quantification of gene expression in tissue samples requires the use of reference genes to normalise transcript numbers between different samples. Reference gene stability may vary between different tissues, and between the same tissue in different disease states. We evaluated the stability of 9 reference genes commonly used in human gene expression studies. Real-time reverse transcription PCR and a mathematical algorithm were used to establish which reference genes were most stably expressed in normal and diseased canine articular tissues and two canine cell lines stimulated with lipolysaccaride (LPS). RESULTS: The optimal reference genes for comparing gene expression data between normal and diseased infrapatella fat pad were RPL13A and YWHAZ (M = 0.56). The ideal reference genes for comparing normal and osteoarthritic (OA) cartilage were RPL13A and SDHA (M = 0.57). The best reference genes for comparing normal and ruptured canine cranial cruciate ligament were B2M and TBP (M = 0.59). The best reference genes for normalising gene expression data from normal and LPS stimulated cell lines were SDHA and YWHAZ (K6) or SDHA and HMBS (DH82), which had expression stability (M) values of 0.05 (K6) and 0.07 (DH82) respectively. The number of reference genes required to reduce pairwise variation (V) to <0.20 was 4 for cell lines, 5 for cartilage, 7 for cranial cruciate ligament and 8 for fat tissue. Reference gene stability was not related to the level of gene expression. CONCLUSION: The reference genes demonstrating the most stable expression within each different canine articular tissue were identified, but no single reference gene was identified as having stable expression in all different tissue types. This study underlines the necessity to select reference genes on the basis of tissue and disease specific expression profile evaluation and highlights the requirement for the identification of new reference genes with greater expression stability for use in canine articular tissue gene expression studies.",2007 May 7,"['Ayers, Duncan', 'Clements, Dylan N', 'Salway, Fiona', 'Day, Philip JR']",BMC Vet Res,,,True
37fe4be4d997e01fa069ab31bbe1a0090356500a,PMC,Early efforts in modeling the incubation period of infectious diseases with an acute course of illness,http://dx.doi.org/10.1186/1742-7622-4-2,PMC1884151,17466070,CC BY,"The incubation period of infectious diseases, the time from infection with a microorganism to onset of disease, is directly relevant to prevention and control. Since explicit models of the incubation period enhance our understanding of the spread of disease, previous classic studies were revisited, focusing on the modeling methods employed and paying particular attention to relatively unknown historical efforts. The earliest study on the incubation period of pandemic influenza was published in 1919, providing estimates of the incubation period of Spanish flu using the daily incidence on ships departing from several ports in Australia. Although the study explicitly dealt with an unknown time of exposure, the assumed periods of exposure, which had an equal probability of infection, were too long, and thus, likely resulted in slight underestimates of the incubation period. After the suggestion that the incubation period follows lognormal distribution, Japanese epidemiologists extended this assumption to estimates of the time of exposure during a point source outbreak. Although the reason why the incubation period of acute infectious diseases tends to reveal a right-skewed distribution has been explored several times, the validity of the lognormal assumption is yet to be fully clarified. At present, various different distributions are assumed, and the lack of validity in assuming lognormal distribution is particularly apparent in the case of slowly progressing diseases. The present paper indicates that (1) analysis using well-defined short periods of exposure with appropriate statistical methods is critical when the exact time of exposure is unknown, and (2) when assuming a specific distribution for the incubation period, comparisons using different distributions are needed in addition to estimations using different datasets, analyses of the determinants of incubation period, and an understanding of the underlying disease mechanisms.",2007 May 11,"Nishiura, Hiroshi",Emerg Themes Epidemiol,,,True
f34b80981d443f5ea437f156a047bfbd66a51090,PMC,Early efforts in modeling the incubation period of infectious diseases with an acute course of illness,http://dx.doi.org/10.1186/1742-7622-4-2,PMC1884151,17466070,CC BY,"The incubation period of infectious diseases, the time from infection with a microorganism to onset of disease, is directly relevant to prevention and control. Since explicit models of the incubation period enhance our understanding of the spread of disease, previous classic studies were revisited, focusing on the modeling methods employed and paying particular attention to relatively unknown historical efforts. The earliest study on the incubation period of pandemic influenza was published in 1919, providing estimates of the incubation period of Spanish flu using the daily incidence on ships departing from several ports in Australia. Although the study explicitly dealt with an unknown time of exposure, the assumed periods of exposure, which had an equal probability of infection, were too long, and thus, likely resulted in slight underestimates of the incubation period. After the suggestion that the incubation period follows lognormal distribution, Japanese epidemiologists extended this assumption to estimates of the time of exposure during a point source outbreak. Although the reason why the incubation period of acute infectious diseases tends to reveal a right-skewed distribution has been explored several times, the validity of the lognormal assumption is yet to be fully clarified. At present, various different distributions are assumed, and the lack of validity in assuming lognormal distribution is particularly apparent in the case of slowly progressing diseases. The present paper indicates that (1) analysis using well-defined short periods of exposure with appropriate statistical methods is critical when the exact time of exposure is unknown, and (2) when assuming a specific distribution for the incubation period, comparisons using different distributions are needed in addition to estimations using different datasets, analyses of the determinants of incubation period, and an understanding of the underlying disease mechanisms.",2007 May 11,"Nishiura, Hiroshi",Emerg Themes Epidemiol,,,False
98d0756af42f78bb74a9df2846729c36ba2f05ad,PMC,Early efforts in modeling the incubation period of infectious diseases with an acute course of illness,http://dx.doi.org/10.1186/1742-7622-4-2,PMC1884151,17466070,CC BY,"The incubation period of infectious diseases, the time from infection with a microorganism to onset of disease, is directly relevant to prevention and control. Since explicit models of the incubation period enhance our understanding of the spread of disease, previous classic studies were revisited, focusing on the modeling methods employed and paying particular attention to relatively unknown historical efforts. The earliest study on the incubation period of pandemic influenza was published in 1919, providing estimates of the incubation period of Spanish flu using the daily incidence on ships departing from several ports in Australia. Although the study explicitly dealt with an unknown time of exposure, the assumed periods of exposure, which had an equal probability of infection, were too long, and thus, likely resulted in slight underestimates of the incubation period. After the suggestion that the incubation period follows lognormal distribution, Japanese epidemiologists extended this assumption to estimates of the time of exposure during a point source outbreak. Although the reason why the incubation period of acute infectious diseases tends to reveal a right-skewed distribution has been explored several times, the validity of the lognormal assumption is yet to be fully clarified. At present, various different distributions are assumed, and the lack of validity in assuming lognormal distribution is particularly apparent in the case of slowly progressing diseases. The present paper indicates that (1) analysis using well-defined short periods of exposure with appropriate statistical methods is critical when the exact time of exposure is unknown, and (2) when assuming a specific distribution for the incubation period, comparisons using different distributions are needed in addition to estimations using different datasets, analyses of the determinants of incubation period, and an understanding of the underlying disease mechanisms.",2007 May 11,"Nishiura, Hiroshi",Emerg Themes Epidemiol,,,True
2616c5aef5cc1449e5a6b07264e1611efc93f4df,PMC,Accurate Reproduction of 161 Small-Molecule Complex Crystal Structures using the EUDOC Program: Expanding the Use of EUDOC to Supramolecular Chemistry,http://dx.doi.org/10.1371/journal.pone.0000531,PMC1888730,17565384,CC BY,"EUDOC is a docking program that has successfully predicted small-molecule-bound protein complexes and identified drug leads from chemical databases. To expand the application of the EUDOC program to supramolecular chemistry, we tested its ability to reproduce crystal structures of small-molecule complexes. Of 161 selected crystal structures of small-molecule guest-host complexes, EUDOC reproduced all these crystal structures with guest structure mass-weighted root mean square deviations (mwRMSDs) of <1.0 Å relative to the corresponding crystal structures. In addition, the average interaction energy of these 161 guest-host complexes (−50.1 kcal/mol) was found to be nearly half of that of 153 previously tested small-molecule-bound protein complexes (−108.5 kcal/mol), according to the interaction energies calculated by EUDOC. 31 of the 161 complexes could not be reproduced with mwRMSDs of <1.0 Å if neighboring hosts in the crystal structure of a guest-host complex were not included as part of the multimeric host system, whereas two of the 161 complexes could not be reproduced with mwRMSDs of <1.0 Å if water molecules were excluded from the host system. These results demonstrate the significant influence of crystal packing on small molecule complexation and suggest that EUDOC is able to predict small-molecule complexes and that it is useful for the design of new materials, molecular sensors, and multimeric inhibitors of protein-protein interactions.",2007 Jun 13,"['Wang, Qi', 'Pang, Yuan-Ping']",PLoS One,,,True
eb07f3436bd925c0de35ecbe26930536e8bcf200,PMC,"Time variations in the transmissibility of pandemic influenza in Prussia, Germany, from 1918–19",http://dx.doi.org/10.1186/1742-4682-4-20,PMC1892008,17547753,CC BY,"BACKGROUND: Time variations in transmission potential have rarely been examined with regard to pandemic influenza. This paper reanalyzes the temporal distribution of pandemic influenza in Prussia, Germany, from 1918–19 using the daily numbers of deaths, which totaled 8911 from 29 September 1918 to 1 February 1919, and the distribution of the time delay from onset to death in order to estimate the effective reproduction number, Rt, defined as the actual average number of secondary cases per primary case at a given time. RESULTS: A discrete-time branching process was applied to back-calculated incidence data, assuming three different serial intervals (i.e. 1, 3 and 5 days). The estimated reproduction numbers exhibited a clear association between the estimates and choice of serial interval; i.e. the longer the assumed serial interval, the higher the reproduction number. Moreover, the estimated reproduction numbers did not decline monotonically with time, indicating that the patterns of secondary transmission varied with time. These tendencies are consistent with the differences in estimates of the reproduction number of pandemic influenza in recent studies; high estimates probably originate from a long serial interval and a model assumption about transmission rate that takes no account of time variation and is applied to the entire epidemic curve. CONCLUSION: The present findings suggest that in order to offer robust assessments it is critically important to clarify in detail the natural history of a disease (e.g. including the serial interval) as well as heterogeneous patterns of transmission. In addition, given that human contact behavior probably influences transmissibility, individual countermeasures (e.g. household quarantine and mask-wearing) need to be explored to construct effective non-pharmaceutical interventions.",2007 Jun 4,"Nishiura, Hiroshi",Theor Biol Med Model,,,True
82946d26f79e85f1b37f6fd965dc1d8a2ceb0c4d,PMC,Cyclooxygenase activity is important for efficient replication of mouse hepatitis virus at an early stage of infection,http://dx.doi.org/10.1186/1743-422X-4-55,PMC1892777,17555580,CC BY,"Cyclooxygenases (COXs) play a significant role in many different viral infections with respect to replication and pathogenesis. Here we investigated the role of COXs in the mouse hepatitis coronavirus (MHV) infection cycle. Blocking COX activity by different inhibitors or by RNA interference affected MHV infection in different cells. The COX inhibitors reduced MHV infection at a post-binding step, but early in the replication cycle. Both viral RNA and viral protein synthesis were affected with subsequent loss of progeny virus production. Thus, COX activity appears to be required for efficient MHV replication, providing a potential target for anti-coronaviral therapy.",2007 Jun 7,"['Raaben, Matthijs', 'Einerhand, Alexandra WC', 'Taminiau, Lucas JA', 'van Houdt, Michel', 'Bouma, Janneke', 'Raatgeep, Rolien H', 'Büller, Hans A', 'de Haan, Cornelis AM', 'Rossen, John WA']",Virol J,,,True
418f1b85e589f3ac37ffc37075b6e558e510fa74,PMC,Designing and conducting tabletop exercises to assess public health preparedness for manmade and naturally occurring biological threats,http://dx.doi.org/10.1186/1471-2458-7-92,PMC1894789,17535426,CC BY,"BACKGROUND: Since 2001, state and local health departments in the United States (US) have accelerated efforts to prepare for high-impact public health emergencies. One component of these activities has been the development and conduct of exercise programs to assess capabilities, train staff and build relationships. This paper summarizes lessons learned from tabletop exercises about public health emergency preparedness and about the process of developing, conducting, and evaluating them. METHODS: We developed, conducted, and evaluated 31 tabletop exercises in partnership with state and local health departments throughout the US from 2003 to 2006. Participant self evaluations, after action reports, and tabletop exercise evaluation forms were used to identify aspects of the exercises themselves, as well as public health emergency responses that participants found more or less challenging, and to highlight lessons learned about tabletop exercise design. RESULTS: Designing the exercises involved substantial collaboration with representatives from participating health departments to assure that the scenarios were credible, focused attention on local preparedness needs and priorities, and were logistically feasible to implement. During execution of the exercises, nearly all health departments struggled with a common set of challenges relating to disease surveillance, epidemiologic investigations, communications, command and control, and health care surge capacity. In contrast, performance strengths were more varied across participating sites, reflecting specific attributes of individual health departments or communities, experience with actual public health emergencies, or the emphasis of prior preparedness efforts. CONCLUSION: The design, conduct, and evaluation of the tabletop exercises described in this report benefited from collaborative planning that involved stakeholders from participating health departments and exercise developers and facilitators from outside the participating agencies. While these exercises identified both strengths and vulnerabilities in emergency preparedness, additional work is needed to develop reliable metrics to gauge exercise performance, inform follow-up action steps, and to develop re-evaluation exercise designs that assess the impact of post-exercise interventions.",2007 May 29,"['Dausey, David J', 'Buehler, James W', 'Lurie, Nicole']",BMC Public Health,,,True
d508ee56bf2773ed13b19b85295c8e8709781bb7,PMC,Population mortality during the outbreak of Severe Acute Respiratory Syndrome in Toronto,http://dx.doi.org/10.1186/1471-2458-7-93,PMC1894965,17535440,CC BY,"BACKGROUND: Extraordinary infection control measures limited access to medical care in the Greater Toronto Area during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak. The objective of this study was to determine if the period of these infection control measures was associated with changes in overall population mortality due to causes other than SARS. METHODS: Observational study of death registry data, using Poisson regression and interrupted time-series analysis to examine all-cause mortality rates (excluding deaths due to SARS) before, during, and after the SARS outbreak. The population of Ontario was grouped into the Greater Toronto Area (N = 2.9 million) and the rest of Ontario (N = 9.3 million) based upon the level of restrictions on delivery of clinical services during the SARS outbreak. RESULTS: There was no significant change in mortality in the Greater Toronto Area before, during, and after the period of the SARS outbreak in 2003 compared to the corresponding time periods in 2002 and 2001. The rate ratio for all-cause mortality during the SARS outbreak was 0.99 [95% Confidence Interval (CI) 0.93–1.06] compared to 2002 and 0.96 [95% CI 0.90–1.03] compared to 2001. An interrupted time series analysis found no significant change in mortality rates in the Greater Toronto Area associated with the period of the SARS outbreak. CONCLUSION: Limitations on access to medical services during the 2003 SARS outbreak in Toronto had no observable impact on short-term population mortality. Effects on morbidity and long-term mortality were not assessed. Efforts to contain future infectious disease outbreaks due to influenza or other agents must consider effects on access to essential health care services.",2007 May 29,"['Hwang, Stephen W', 'Cheung, Angela M', 'Moineddin, Rahim', 'Bell, Chaim M']",BMC Public Health,,,True
fe8ae98f3112f0ecf862177dd5745232b9d1f966,PMC,An Epidemiological Network Model for Disease Outbreak Detection,http://dx.doi.org/10.1371/journal.pmed.0040210,PMC1896205,17593895,CC BY,"BACKGROUND: Advanced disease-surveillance systems have been deployed worldwide to provide early detection of infectious disease outbreaks and bioterrorist attacks. New methods that improve the overall detection capabilities of these systems can have a broad practical impact. Furthermore, most current generation surveillance systems are vulnerable to dramatic and unpredictable shifts in the health-care data that they monitor. These shifts can occur during major public events, such as the Olympics, as a result of population surges and public closures. Shifts can also occur during epidemics and pandemics as a result of quarantines, the worried-well flooding emergency departments or, conversely, the public staying away from hospitals for fear of nosocomial infection. Most surveillance systems are not robust to such shifts in health-care utilization, either because they do not adjust baselines and alert-thresholds to new utilization levels, or because the utilization shifts themselves may trigger an alarm. As a result, public-health crises and major public events threaten to undermine health-surveillance systems at the very times they are needed most. METHODS AND FINDINGS: To address this challenge, we introduce a class of epidemiological network models that monitor the relationships among different health-care data streams instead of monitoring the data streams themselves. By extracting the extra information present in the relationships between the data streams, these models have the potential to improve the detection capabilities of a system. Furthermore, the models' relational nature has the potential to increase a system's robustness to unpredictable baseline shifts. We implemented these models and evaluated their effectiveness using historical emergency department data from five hospitals in a single metropolitan area, recorded over a period of 4.5 y by the Automated Epidemiological Geotemporal Integrated Surveillance real-time public health–surveillance system, developed by the Children's Hospital Informatics Program at the Harvard-MIT Division of Health Sciences and Technology on behalf of the Massachusetts Department of Public Health. We performed experiments with semi-synthetic outbreaks of different magnitudes and simulated baseline shifts of different types and magnitudes. The results show that the network models provide better detection of localized outbreaks, and greater robustness to unpredictable shifts than a reference time-series modeling approach. CONCLUSIONS: The integrated network models of epidemiological data streams and their interrelationships have the potential to improve current surveillance efforts, providing better localized outbreak detection under normal circumstances, as well as more robust performance in the face of shifts in health-care utilization during epidemics and major public events.",2007 Jun 26,"['Reis, Ben Y', 'Kohane, Isaac S', 'Mandl, Kenneth D']",PLoS Med,,,True
853fa72687a51e0a938d05ef0c6c6fde3fbc361f,PMC,The association of RANTES polymorphism with severe acute respiratory syndrome in Hong Kong and Beijing Chinese,http://dx.doi.org/10.1186/1471-2334-7-50,PMC1899505,17540042,CC BY,"BACKGROUND: Chemokines play important roles in inflammation and antiviral action. We examined whether polymorphisms of RANTES, IP-10 and Mig affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). METHODS: We tested the polymorphisms of RANTES, IP-10 and Mig for their associations with SARS in 495 Hong Kong Chinese SARS patients and 578 controls. Then we tried to confirm the results in 356 Beijing Chinese SARS patients and 367 controls. RESULTS: RANTES -28 G allele was associated with SARS susceptibility in Hong Kong Chinese (P < 0.0001, OR = 2.80, 95%CI:2.11–3.71). Individuals with RANTES -28 CG and GG genotypes had a 3.28-fold (95%CI:2.32–4.64) and 3.06-fold (95%CI:1.47–6.39) increased risk of developing SARS respectively (P < 0.0001). This -28 G allele conferred risk of death in a gene-dosage dependent manner (P = 0.014) with CG and GG individuals having a 2.12-fold (95% CI: 1.11–4.06) and 4.01-fold (95% CI: 1.30–12.4) increased risk. For the replication of RANTES data in Beijing Chinese, the -28 G allele was not associated with susceptibility to SARS. However, -28 CG (OR = 4.27, 95%CI:1.64–11.1) and GG (OR = 3.34, 95%CI:0.37–30.7) were associated with admission to intensive care units or death due to SARS (P = 0.011). CONCLUSION: RANTES -28 G allele plays a role in the pathogenesis of SARS.",2007 Jun 1,"['Ng, Man Wai', 'Zhou, Gangqiao', 'Chong, Wai Po', 'Lee, Loretta Wing Yan', 'Law, Helen Ka Wai', 'Zhang, Hongxing', 'Wong, Wilfred Hing Sang', 'Fok, Susanna Fung Shan', 'Zhai, Yun', 'Yung, Raymond WH', 'Chow, Eudora Y', 'Au, Ka Leung', 'Chan, Eric YT', 'Lim, Wilina', 'Peiris, JS Malik', 'He, Fuchu', 'Lau, Yu Lung']",BMC Infect Dis,,,True
8f7db32196a87deaa43589b325f60156efc5a63a,PMC,Transfusion-transmitted infections,http://dx.doi.org/10.1186/1479-5876-5-25,PMC1904179,17553144,CC BY,"Although the risk of transfusion-transmitted infections today is lower than ever, the supply of safe blood products remains subject to contamination with known and yet to be identified human pathogens. Only continuous improvement and implementation of donor selection, sensitive screening tests and effective inactivation procedures can ensure the elimination, or at least reduction, of the risk of acquiring transfusion transmitted infections. In addition, ongoing education and up-to-date information regarding infectious agents that are potentially transmitted via blood components is necessary to promote the reporting of adverse events, an important component of transfusion transmitted disease surveillance. Thus, the collaboration of all parties involved in transfusion medicine, including national haemovigilance systems, is crucial for protecting a secure blood product supply from known and emerging blood-borne pathogens.",2007 Jun 6,"['Bihl, Florian', 'Castelli, Damiano', 'Marincola, Francesco', 'Dodd, Roger Y', 'Brander, Christian']",J Transl Med,,,True
2bf62ecb50fd95973de0bf6c1285ac3475fc4cc8,PMC,Transcript-level annotation of Affymetrix probesets improves the interpretation of gene expression data,http://dx.doi.org/10.1186/1471-2105-8-194,PMC1913542,17559689,CC BY,"BACKGROUND: The wide use of Affymetrix microarray in broadened fields of biological research has made the probeset annotation an important issue. Standard Affymetrix probeset annotation is at gene level, i.e. a probeset is precisely linked to a gene, and probeset intensity is interpreted as gene expression. The increased knowledge that one gene may have multiple transcript variants clearly brings up the necessity of updating this gene-level annotation to a refined transcript-level. RESULTS: Through performing rigorous alignments of the Affymetrix probe sequences against a comprehensive pool of currently available transcript sequences, and further linking the probesets to the International Protein Index, we generated transcript-level or protein-level annotation tables for two popular Affymetrix expression arrays, Mouse Genome 430A 2.0 Array and Human Genome U133A Array. Application of our new annotations in re-examining existing expression data sets shows increased expression consistency among synonymous probesets and strengthened expression correlation between interacting proteins. CONCLUSION: By refining the standard Affymetrix annotation of microarray probesets from the gene level to the transcript level and protein level, one can achieve a more reliable interpretation of their experimental data, which may lead to discovery of more profound regulatory mechanism.",2007 Jun 11,"['Yu, Hui', 'Wang, Feng', 'Tu, Kang', 'Xie, Lu', 'Li, Yuan-Yuan', 'Li, Yi-Xue']",BMC Bioinformatics,,,True
2ddd50da1dd398931c5db3d1734948ef27b705bd,PMC,Automated real time constant-specificity surveillance for disease outbreaks,http://dx.doi.org/10.1186/1472-6947-7-15,PMC1919360,17567912,CC BY,"BACKGROUND: For real time surveillance, detection of abnormal disease patterns is based on a difference between patterns observed, and those predicted by models of historical data. The usefulness of outbreak detection strategies depends on their specificity; the false alarm rate affects the interpretation of alarms. RESULTS: We evaluate the specificity of five traditional models: autoregressive, Serfling, trimmed seasonal, wavelet-based, and generalized linear. We apply each to 12 years of emergency department visits for respiratory infection syndromes at a pediatric hospital, finding that the specificity of the five models was almost always a non-constant function of the day of the week, month, and year of the study (p < 0.05). We develop an outbreak detection method, called the expectation-variance model, based on generalized additive modeling to achieve a constant specificity by accounting for not only the expected number of visits, but also the variance of the number of visits. The expectation-variance model achieves constant specificity on all three time scales, as well as earlier detection and improved sensitivity compared to traditional methods in most circumstances. CONCLUSION: Modeling the variance of visit patterns enables real-time detection with known, constant specificity at all times. With constant specificity, public health practitioners can better interpret the alarms and better evaluate the cost-effectiveness of surveillance systems.",2007 Jun 13,"['Wieland, Shannon C', 'Brownstein, John S', 'Berger, Bonnie', 'Mandl, Kenneth D']",BMC Med Inform Decis Mak,,,True
8309dc172cf91ff580779bbc1394a9692b798a86,PMC,Screen for ISG15-crossreactive Deubiquitinases,http://dx.doi.org/10.1371/journal.pone.0000679,PMC1919423,17653289,CC BY,"BACKGROUND: The family of ubiquitin-like molecules (UbLs) comprises several members, each of which has sequence, structural, or functional similarity to ubiquitin. ISG15 is a homolog of ubiquitin in vertebrates and is strongly upregulated following induction by type I interferon. ISG15 can be covalently attached to proteins, analogous to ubiquitination and with actual support of ubiquitin conjugating factors. Specific proteases are able to reverse modification with ubiquitin or UbLs by hydrolyzing the covalent bond between their C-termini and substrate proteins. The tail regions of ubiquitin and ISG15 are identical and we therefore hypothesized that promiscuous deubiquitinating proteases (DUBs) might exist, capable of recognizing both ubiquitin and ISG15. RESULTS: We have cloned and expressed 22 human DUBs, representing the major clades of the USP protease family. Utilizing suicide inhibitors based on ubiquitin and ISG15, we have identified USP2, USP5 (IsoT1), USP13 (IsoT3), and USP14 as ISG15-reactive proteases, in addition to the bona fide ISG15-specific protease USP18 (UBP43). USP14 is a proteasome-associated DUB, and its ISG15 isopeptidase activity increases when complexed with the proteasome. CONCLUSIONS: By evolutionary standards, ISG15 is a newcomer among the UbLs and it apparently not only utilizes the conjugating but also the deconjugating machinery of its more established relative ubiquitin. Functional overlap between these two posttranslational modifiers might therefore be more extensive than previously appreciated and explain the rather innocuous phenotype of ISG15 null mice.",2007 Jul 25,"['Catic, André', 'Fiebiger, Edda', 'Korbel, Gregory A.', 'Blom, Daniël', 'Galardy, Paul J.', 'Ploegh, Hidde L.']",PLoS One,,,True
4994fa72322bbf19120592304d92629226948d8e,PMC,Rapid Identification of Malaria Vaccine Candidates Based on α-Helical Coiled Coil Protein Motif,http://dx.doi.org/10.1371/journal.pone.0000645,PMC1920550,17653272,CC BY,"To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. The corresponding synthetic peptides are expected to mimic structurally “native” epitopes. Indeed the 95 chemically synthesized peptides were all specifically recognized by human immune sera, though at various prevalence. Peptide specific antibodies were obtained both by affinity-purification from malaria immune sera and by immunization of mice. These antibodies did not show significant cross reactions, i.e., they were specific for the original peptide, reacted with native parasite proteins in infected erythrocytes and several were active in inhibiting in vitro parasite growth. Circular dichroism studies indicated that the selected peptides assumed partial or high α-helical content. Thus, we demonstrate that the bioinformatics/chemical synthesis approach described here can lead to the rapid identification of molecules which target biologically active antibodies, thus identifying suitable vaccine candidates. This strategy can be, in principle, extended to vaccine discovery in a wide range of other pathogens.",2007 Jul 25,"['Villard, Viviane', 'Agak, George W.', 'Frank, Géraldine', 'Jafarshad, Ali', 'Servis, Catherine', 'Nébié, Issa', 'Sirima, Sodiomon B.', 'Felger, Ingrid', 'Arevalo-Herrera, Myriam', 'Herrera, Socrates', 'Heitz, Frederic', 'Bäcker, Volker', 'Druilhe, Pierre', 'Kajava, Andrey V.', 'Corradin, Giampietro']",PLoS One,,,True
deeacb8558e3403c69cd8db9f4e8e5214fd85c46,PMC,Identification and characterisation of the angiotensin converting enzyme-3 (ACE3) gene: a novel mammalian homologue of ACE,http://dx.doi.org/10.1186/1471-2164-8-194,PMC1925091,17597519,CC BY,"BACKGROUND: Mammalian angiotensin converting enzyme (ACE) plays a key role in blood pressure regulation. Although multiple ACE-like proteins exist in non-mammalian organisms, to date only one other ACE homologue, ACE2, has been identified in mammals. RESULTS: Here we report the identification and characterisation of the gene encoding a third homologue of ACE, termed ACE3, in several mammalian genomes. The ACE3 gene is located on the same chromosome downstream of the ACE gene. Multiple sequence alignment and molecular modelling have been employed to characterise the predicted ACE3 protein. In mouse, rat, cow and dog, the predicted protein has mutations in some of the critical residues involved in catalysis, including the catalytic Glu in the HEXXH zinc binding motif which is Gln, and ESTs or reverse-transcription PCR indicate that the gene is expressed. In humans, the predicted ACE3 protein has an intact HEXXH motif, but there are other deletions and insertions in the gene and no ESTs have been identified. CONCLUSION: In the genomes of several mammalian species there is a gene that encodes a novel, single domain ACE-like protein, ACE3. In mouse, rat, cow and dog ACE3, the catalytic Glu is replaced by Gln in the putative zinc binding motif, indicating that in these species ACE3 would lack catalytic activity as a zinc metalloprotease. In humans, no evidence was found that the ACE3 gene is expressed and the presence of deletions and insertions in the sequence indicate that ACE3 is a pseudogene.",2007 Jun 27,"['Rella, Monika', 'Elliot, Joann L', 'Revett, Timothy J', 'Lanfear, Jerry', 'Phelan, Anne', 'Jackson, Richard M', 'Turner, Anthony J', 'Hooper, Nigel M']",BMC Genomics,,,True
40e94ea7aba6cfaed881217032da16d4a5c2fd1d,PMC,Optimization and clinical validation of a pathogen detection microarray,http://dx.doi.org/10.1186/gb-2007-8-5-r93,PMC1929155,17531104,CC BY,"DNA microarrays used as 'genomic sensors' have great potential in clinical diagnostics. Biases inherent in random PCR-amplification, cross-hybridization effects, and inadequate microarray analysis, however, limit detection sensitivity and specificity. Here, we have studied the relationships between viral amplification efficiency, hybridization signal, and target-probe annealing specificity using a customized microarray platform. Novel features of this platform include the development of a robust algorithm that accurately predicts PCR bias during DNA amplification and can be used to improve PCR primer design, as well as a powerful statistical concept for inferring pathogen identity from probe recognition signatures. Compared to real-time PCR, the microarray platform identified pathogens with 94% accuracy (76% sensitivity and 100% specificity) in a panel of 36 patient specimens. Our findings show that microarrays can be used for the robust and accurate diagnosis of pathogens, and further substantiate the use of microarray technology in clinical diagnostics.",2007 May 28,"['Wong, Christopher W', 'Heng, Charlie Lee Wah', 'Wan Yee, Leong', 'Soh, Shirlena WL', 'Kartasasmita, Cissy B', 'Simoes, Eric AF', 'Hibberd, Martin L', 'Sung, Wing-Kin', 'Miller, Lance D']",Genome Biol,,,True
25a348f34236403317091db876b29fd5063528ed,PMC,Influenza pandemic preparedness: motivation for protection among small and medium businesses in Australia,http://dx.doi.org/10.1186/1471-2458-7-157,PMC1934907,17634112,CC BY,"BACKGROUND: Community-wide preparedness for pandemic influenza is an issue that has featured prominently in the recent news media, and is currently a priority for health authorities in many countries. The small and medium business sector is a major provider of private sector employment in Australia, yet we have little information about the preparedness of this sector for pandemic influenza. This study aimed to investigate the association between individual perceptions and preparedness for pandemic influenza among small and medium business owners and managers. METHODS: Semi-structured face-to-face interviews were conducted with 201 small and medium business owners or managers in New South Wales and Western Australia. Eligible small or medium businesses were defined as those that had less than 200 employees. Binomial logistic regression analysis was used to identify the predictors of having considered the impact of, having a plan for, and needing help to prepare for pandemic influenza. RESULTS: Approximately 6 per cent of participants reported that their business had a plan for pandemic influenza, 39 per cent reported that they had not thought at all about the impact of pandemic influenza on their business, and over 60 per cent stated that they required help to prepare for a pandemic. Beliefs about the severity of pandemic influenza and the ability to respond were significant independent predictors of having a plan for pandemic influenza, and the perception of the risk of pandemic influenza was the most important predictor of both having considered the impact of, and needing help to prepare for a pandemic. CONCLUSION: Our findings suggest that small and medium businesses in Australia are not currently well prepared for pandemic influenza. We found that beliefs about the risk, severity, and the ability to respond effectively to the threat of pandemic influenza are important predictors of preparedness. Campaigns targeting small and medium businesses should emphasise the severity of the consequences to their businesses if a pandemic were to occur, and, at the same time, reassure them that there are effective strategies capable of being implemented by small and medium businesses to deal with a pandemic.",2007 Jul 17,"['Watkins, Rochelle E', 'Cooke, Feonagh C', 'Donovan, Robert J', 'MacIntyre, C Raina', 'Itzwerth, Ralf', 'Plant, Aileen J']",BMC Public Health,,,True
555bbbbd23da02c97c6a4238937e31b5781438a9,PMC,Influenza pandemic intervention planning using InfluSim: pharmaceutical and non- pharmaceutical interventions,http://dx.doi.org/10.1186/1471-2334-7-76,PMC1939851,17629919,CC BY,"BACKGROUND: Influenza pandemic preparedness plans are currently developed and refined on national and international levels. Much attention has been given to the administration of antiviral drugs, but contact reduction can also be an effective part of mitigation strategies and has the advantage to be not limited per se. The effectiveness of these interventions depends on various factors which must be explored by sensitivity analyses, based on mathematical models. METHODS: We use the freely available planning tool InfluSim to investigate how pharmaceutical and non-pharmaceutical interventions can mitigate an influenza pandemic. In particular, we examine how intervention schedules, restricted stockpiles and contact reduction (social distancing measures and isolation of cases) determine the course of a pandemic wave and the success of interventions. RESULTS: A timely application of antiviral drugs combined with a quick implementation of contact reduction measures is required to substantially protract the peak of the epidemic and reduce its height. Delays in the initiation of antiviral treatment (e.g. because of parsimonious use of a limited stockpile) result in much more pessimistic outcomes and can even lead to the paradoxical effect that the stockpile is depleted earlier compared to early distribution of antiviral drugs. CONCLUSION: Pharmaceutical and non-pharmaceutical measures should not be used exclusively. The protraction of the pandemic wave is essential to win time while waiting for vaccine development and production. However, it is the height of the peak of an epidemic which can easily overtax general practitioners, hospitals or even whole public health systems, causing bottlenecks in basic and emergency medical care.",2007 Jul 13,"['Duerr, Hans P', 'Brockmann, Stefan O', 'Piechotowski, Isolde', 'Schwehm, Markus', 'Eichner, Martin']",BMC Infect Dis,,,True
a5701c6fbac36d0fcac9dc32cd78288f3f27f24b,PMC,Factor structure of the General Health Questionnaire (GHQ-12) in subjects who had suffered from the 2004 Niigata-Chuetsu Earthquake in Japan: a community-based study,http://dx.doi.org/10.1186/1471-2458-7-175,PMC1939990,17650342,CC BY,"BACKGROUND: Factor structure of the 12-item General Health Questionnaire (GHQ-12) was studied by a survey of subjects who had experienced the 2004 Niigata-Chuetsu earthquake (6.8 on the Richter scale) in Japan. METHODS: Psychological distress was measured at two years after the earthquake by using GHQ-12 in 2,107 subjects (99.0% response rate) who suffered the earthquake. GHQ-12 was scored by binary, chronic and Likert scoring method. Confirmatory factor analysis was used to reveal the factor structure of GHQ-12. Categorical regression analysis was performed to evaluate the relationships between various background factors and GHQ-12 scores. RESULTS: Confirmatory factor analysis revealed that the model consisting of the two factors and using chronic method gave the best goodness-of-fit among the various models for factor structure. Recovery in the scale for the factor 'social dysfunction' was remarkably impaired compared with that of the factor 'dysphoria'. Categorical regression analysis revealed that various factors, including advanced age, were associated with psychological distress. Advanced age affected the impaired recovery of factor 'social dysfunction' score as well as total GHQ score. CONCLUSION: The two-factor structure of GHQ-12 was conserved between the survey at five month and that at two years after the earthquake. Impaired recovery in the ability to cope with daily problems in the subjects who had experienced the earthquake was remarkable even at two years after the earthquake.",2007 Jul 24,"['Toyabe, Shin-ichi', 'Shioiri, Toshiki', 'Kobayashi, Kuriko', 'Kuwabara, Hideki', 'Koizumi, Masataka', 'Endo, Taro', 'Ito, Miki', 'Honma, Hiroko', 'Fukushima, Noboru', 'Someya, Toshiyuki', 'Akazawa, Kouhei']",BMC Public Health,,,True
c99be1ffda777de5b7f9e0ed6c04fd70ce0bc3e1,PMC,Coronavirus Non-Structural Protein 1 Is a Major Pathogenicity Factor: Implications for the Rational Design of Coronavirus Vaccines,http://dx.doi.org/10.1371/journal.ppat.0030109,PMC1941747,17696607,CC BY,"Attenuated viral vaccines can be generated by targeting essential pathogenicity factors. We report here the rational design of an attenuated recombinant coronavirus vaccine based on a deletion in the coding sequence of the non-structural protein 1 (nsp1). In cell culture, nsp1 of mouse hepatitis virus (MHV), like its SARS-coronavirus homolog, strongly reduced cellular gene expression. The effect of nsp1 on MHV replication in vitro and in vivo was analyzed using a recombinant MHV encoding a deletion in the nsp1-coding sequence. The recombinant MHV nsp1 mutant grew normally in tissue culture, but was severely attenuated in vivo. Replication and spread of the nsp1 mutant virus was restored almost to wild-type levels in type I interferon (IFN) receptor-deficient mice, indicating that nsp1 interferes efficiently with the type I IFN system. Importantly, replication of nsp1 mutant virus in professional antigen-presenting cells such as conventional dendritic cells and macrophages, and induction of type I IFN in plasmacytoid dendritic cells, was not impaired. Furthermore, even low doses of nsp1 mutant MHV elicited potent cytotoxic T cell responses and protected mice against homologous and heterologous virus challenge. Taken together, the presented attenuation strategy provides a paradigm for the development of highly efficient coronavirus vaccines.",2007 Aug 10,"['Züst, Roland', 'Cervantes-Barragán, Luisa', 'Kuri, Thomas', 'Blakqori, Gjon', 'Weber, Friedemann', 'Ludewig, Burkhard', 'Thiel, Volker']",PLoS Pathog,,,True
0e24e06b66ebf676c3d15bbcaf7120dc60413702,PMC,Functional Genomics Highlights Differential Induction of Antiviral Pathways in the Lungs of SARS-CoV–Infected Macaques,http://dx.doi.org/10.1371/journal.ppat.0030112,PMC1941749,17696609,CC BY,"The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis) that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL)-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs) and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS.",2007 Aug 10,"['de Lang, Anna', 'Baas, Tracey', 'Teal, Thomas', 'Leijten, Lonneke M', 'Rain, Brandon', 'Osterhaus, Albert D', 'Haagmans, Bart L', 'Katze, Michael G']",PLoS Pathog,,,True
77a8c567572cf005f58dc577dc44f711aabe3fd4,PMC,Three-Dimensional Analysis of a Viral RNA Replication Complex Reveals a Virus-Induced Mini-Organelle,http://dx.doi.org/10.1371/journal.pbio.0050220,PMC1945040,17696647,CC BY,"Positive-strand RNA viruses are the largest genetic class of viruses and include many serious human pathogens. All positive-strand RNA viruses replicate their genomes in association with intracellular membrane rearrangements such as single- or double-membrane vesicles. However, the exact sites of RNA synthesis and crucial topological relationships between relevant membranes, vesicle interiors, surrounding lumens, and cytoplasm generally are poorly defined. We applied electron microscope tomography and complementary approaches to flock house virus (FHV)–infected Drosophila cells to provide the first 3-D analysis of such replication complexes. The sole FHV RNA replication factor, protein A, and FHV-specific 5-bromouridine 5'-triphosphate incorporation localized between inner and outer mitochondrial membranes inside ∼50-nm vesicles (spherules), which thus are FHV-induced compartments for viral RNA synthesis. All such FHV spherules were outer mitochondrial membrane invaginations with interiors connected to the cytoplasm by a necked channel of ∼10-nm diameter, which is sufficient for ribonucleotide import and product RNA export. Tomographic, biochemical, and other results imply that FHV spherules contain, on average, three RNA replication intermediates and an interior shell of ∼100 membrane-spanning, self-interacting protein As. The results identify spherules as the site of protein A and nascent RNA accumulation and define spherule topology, dimensions, and stoichiometry to reveal the nature and many details of the organization and function of the FHV RNA replication complex. The resulting insights appear relevant to many other positive-strand RNA viruses and support recently proposed structural and likely evolutionary parallels with retrovirus and double-stranded RNA virus virions.",2007 Sep 14,"['Kopek, Benjamin G', 'Perkins, Guy', 'Miller, David J', 'Ellisman, Mark H', 'Ahlquist, Paul']",PLoS Biol,,,True
b6eed04e43ad653c06247b10ab05d03bdccf04bc,PMC,Estimating Individual and Household Reproduction Numbers in an Emerging Epidemic,http://dx.doi.org/10.1371/journal.pone.0000758,PMC1950082,17712406,CC BY,"Reproduction numbers, defined as averages of the number of people infected by a typical case, play a central role in tracking infectious disease outbreaks. The aim of this paper is to develop methods for estimating reproduction numbers which are simple enough that they could be applied with limited data or in real time during an outbreak. I present a new estimator for the individual reproduction number, which describes the state of the epidemic at a point in time rather than tracking individuals over time, and discuss some potential benefits. Then, to capture more of the detail that micro-simulations have shown is important in outbreak dynamics, I analyse a model of transmission within and between households, and develop a method to estimate the household reproduction number, defined as the number of households infected by each infected household. This method is validated by numerical simulations of the spread of influenza and measles using historical data, and estimates are obtained for would-be emerging epidemics of these viruses. I argue that the household reproduction number is useful in assessing the impact of measures that target the household for isolation, quarantine, vaccination or prophylactic treatment, and measures such as social distancing and school or workplace closures which limit between-household transmission, all of which play a key role in current thinking on future infectious disease mitigation.",2007 Aug 22,"Fraser, Christophe",PLoS One,,,True
aa244b14aba85cb4dc31dedbf92e9d6ac1dd25f3,PMC,Estimating Individual and Household Reproduction Numbers in an Emerging Epidemic,http://dx.doi.org/10.1371/journal.pone.0000758,PMC1950082,17712406,CC BY,"Reproduction numbers, defined as averages of the number of people infected by a typical case, play a central role in tracking infectious disease outbreaks. The aim of this paper is to develop methods for estimating reproduction numbers which are simple enough that they could be applied with limited data or in real time during an outbreak. I present a new estimator for the individual reproduction number, which describes the state of the epidemic at a point in time rather than tracking individuals over time, and discuss some potential benefits. Then, to capture more of the detail that micro-simulations have shown is important in outbreak dynamics, I analyse a model of transmission within and between households, and develop a method to estimate the household reproduction number, defined as the number of households infected by each infected household. This method is validated by numerical simulations of the spread of influenza and measles using historical data, and estimates are obtained for would-be emerging epidemics of these viruses. I argue that the household reproduction number is useful in assessing the impact of measures that target the household for isolation, quarantine, vaccination or prophylactic treatment, and measures such as social distancing and school or workplace closures which limit between-household transmission, all of which play a key role in current thinking on future infectious disease mitigation.",2007 Aug 22,"Fraser, Christophe",PLoS One,,,False
86febf1edc351777b6424be2ee9a2e521176dd98,PMC,Virus detection and identification using random multiplex (RT)-PCR with 3'-locked random primers,http://dx.doi.org/10.1186/1743-422X-4-65,PMC1950496,17598900,CC BY,"BACKGROUND: PCR-based detection and identification of viruses assumes a known, relatively stable genome. Unfortunately, high mutation rates may lead to extensive changes in viral nucleic acid sequences making dedicated PCR primer use problematic. Furthermore, in bioterrorism, viral consensus sequences can be genetically modified as a countermeasure to RT-PCR and DNA chip detection. Accordingly, there is a great need for the development of rapid and universal virus detection and identification technologies. RESULTS: We report herein that viral genomic DNA or RNA can be separated from host nucleic acids in plasma by filtration and nuclease digestion, and randomly amplified in a single PCR using a mixture of primers designed to be resistant to primer-dimer amplification (5'-VVVVVVVVAA-3', V = A, G or C; 3(8 )or 6561 primers). We have termed this novel PCR method Random Multiplex (RT)-PCR since hundreds of overlapping PCR amplifications occur simultaneously. Using this method, we have successfullydetected and partially sequenced 3 separate viruses in human plasma without using virus-specific reagents (i.e., Adenovirus Type 17, Coxsackievirus A7, and Respiratory Syncytial Virus B). The method is sensitive to ~1000 genome equivalents/ml and may represent the fastest means of detection of unknown viruses. CONCLUSION: These studies suggest that the further development of random multiplex (RT)-PCR may lead to a diagnostic assay that can universally detect viruses in donated blood products as well as in patients suffering with idiopathic disease states of possible viral etiology.",2007 Jun 28,"['Clem, Amy L', 'Sims, Jonathan', 'Telang, Sucheta', 'Eaton, John W', 'Chesney, Jason']",Virol J,,,True
fb3c146b1766b4aa33df1637742bf93159967289,PMC,Natural Killer Cells Promote Early CD8 T Cell Responses against Cytomegalovirus,http://dx.doi.org/10.1371/journal.ppat.0030123,PMC1950948,17722980,CC BY,"Understanding the mechanisms that help promote protective immune responses to pathogens is a major challenge in biomedical research and an important goal for the design of innovative therapeutic or vaccination strategies. While natural killer (NK) cells can directly contribute to the control of viral replication, whether, and how, they may help orchestrate global antiviral defense is largely unknown. To address this question, we took advantage of the well-defined molecular interactions involved in the recognition of mouse cytomegalovirus (MCMV) by NK cells. By using congenic or mutant mice and wild-type versus genetically engineered viruses, we examined the consequences on antiviral CD8 T cell responses of specific defects in the ability of the NK cells to control MCMV. This system allowed us to demonstrate, to our knowledge for the first time, that NK cells accelerate CD8 T cell responses against a viral infection in vivo. Moreover, we identify the underlying mechanism as the ability of NK cells to limit IFN-α/β production to levels not immunosuppressive to the host. This is achieved through the early control of cytomegalovirus, which dramatically reduces the activation of plasmacytoid dendritic cells (pDCs) for cytokine production, preserves the conventional dendritic cell (cDC) compartment, and accelerates antiviral CD8 T cell responses. Conversely, exogenous IFN-α administration in resistant animals ablates cDCs and delays CD8 T cell activation in the face of NK cell control of viral replication. Collectively, our data demonstrate that the ability of NK cells to respond very early to cytomegalovirus infection critically contributes to balance the intensity of other innate immune responses, which dampens early immunopathology and promotes optimal initiation of antiviral CD8 T cell responses. Thus, the extent to which NK cell responses benefit the host goes beyond their direct antiviral effects and extends to the prevention of innate cytokine shock and to the promotion of adaptive immunity.",2007 Aug 24,"['Robbins, Scott H', 'Bessou, Gilles', 'Cornillon, Amélie', 'Zucchini, Nicolas', 'Rupp, Brigitte', 'Ruzsics, Zsolt', 'Sacher, Torsten', 'Tomasello, Elena', 'Vivier, Eric', 'Koszinowski, Ulrich H', 'Dalod, Marc']",PLoS Pathog,,,True
b0218dd5c965f2c92348a50f46ea2e271a56c7c8,PMC,Persistent Infection and Promiscuous Recombination of Multiple Genotypes of an RNA Virus within a Single Host Generate Extensive Diversity,http://dx.doi.org/10.1371/journal.pone.0000917,PMC1975466,17878952,CC BY,"Recombination and reassortment of viral genomes are major processes contributing to the creation of new, emerging viruses. These processes are especially significant in long-term persistent infections where multiple viral genotypes co-replicate in a single host, generating abundant genotypic variants, some of which may possess novel host-colonizing and pathogenicity traits. In some plants, successive vegetative propagation of infected tissues and introduction of new genotypes of a virus by vector transmission allows for viral populations to increase in complexity for hundreds of years allowing co-replication and subsequent recombination of the multiple viral genotypes. Using a resequencing microarray, we examined a persistent infection by a Citrus tristeza virus (CTV) complex in citrus, a vegetatively propagated, globally important fruit crop, and found that the complex comprised three major and a number of minor genotypes. Subsequent deep sequencing analysis of the viral population confirmed the presence of the three major CTV genotypes and, in addition, revealed that the minor genotypes consisted of an extraordinarily large number of genetic variants generated by promiscuous recombination between the major genotypes. Further analysis provided evidence that some of the recombinants underwent subsequent divergence, further increasing the genotypic complexity. These data demonstrate that persistent infection of multiple viral genotypes within a host organism is sufficient to drive the large-scale production of viral genetic variants that may evolve into new and emerging viruses.",2007 Sep 19,"['Weng, Ziming', 'Barthelson, Roger', 'Gowda, Siddarame', 'Hilf, Mark E.', 'Dawson, William O.', 'Galbraith, David W.', 'Xiong, Zhongguo']",PLoS One,,,True
c235de11eceb5f9f55e0b361818e959d4482b621,PMC,Persistent Infection and Promiscuous Recombination of Multiple Genotypes of an RNA Virus within a Single Host Generate Extensive Diversity,http://dx.doi.org/10.1371/journal.pone.0000917,PMC1975466,17878952,CC BY,"Recombination and reassortment of viral genomes are major processes contributing to the creation of new, emerging viruses. These processes are especially significant in long-term persistent infections where multiple viral genotypes co-replicate in a single host, generating abundant genotypic variants, some of which may possess novel host-colonizing and pathogenicity traits. In some plants, successive vegetative propagation of infected tissues and introduction of new genotypes of a virus by vector transmission allows for viral populations to increase in complexity for hundreds of years allowing co-replication and subsequent recombination of the multiple viral genotypes. Using a resequencing microarray, we examined a persistent infection by a Citrus tristeza virus (CTV) complex in citrus, a vegetatively propagated, globally important fruit crop, and found that the complex comprised three major and a number of minor genotypes. Subsequent deep sequencing analysis of the viral population confirmed the presence of the three major CTV genotypes and, in addition, revealed that the minor genotypes consisted of an extraordinarily large number of genetic variants generated by promiscuous recombination between the major genotypes. Further analysis provided evidence that some of the recombinants underwent subsequent divergence, further increasing the genotypic complexity. These data demonstrate that persistent infection of multiple viral genotypes within a host organism is sufficient to drive the large-scale production of viral genetic variants that may evolve into new and emerging viruses.",2007 Sep 19,"['Weng, Ziming', 'Barthelson, Roger', 'Gowda, Siddarame', 'Hilf, Mark E.', 'Dawson, William O.', 'Galbraith, David W.', 'Xiong, Zhongguo']",PLoS One,,,True
8d14b700a065187eb4d8b01e0e9b6e3e37e5d09b,PMC,Prediction of RNA Pseudoknots Using Heuristic Modeling with Mapping and Sequential Folding,http://dx.doi.org/10.1371/journal.pone.0000905,PMC1975678,17878940,CC BY,"Predicting RNA secondary structure is often the first step to determining the structure of RNA. Prediction approaches have historically avoided searching for pseudoknots because of the extreme combinatorial and time complexity of the problem. Yet neglecting pseudoknots limits the utility of such approaches. Here, an algorithm utilizing structure mapping and thermodynamics is introduced for RNA pseudoknot prediction that finds the minimum free energy and identifies information about the flexibility of the RNA. The heuristic approach takes advantage of the 5′ to 3′ folding direction of many biological RNA molecules and is consistent with the hierarchical folding hypothesis and the contact order model. Mapping methods are used to build and analyze the folded structure for pseudoknots and to add important 3D structural considerations. The program can predict some well known pseudoknot structures correctly. The results of this study suggest that many functional RNA sequences are optimized for proper folding. They also suggest directions we can proceed in the future to achieve even better results.",2007 Sep 19,"['Dawson, Wayne K.', 'Fujiwara, Kazuya', 'Kawai, Gota']",PLoS One,,,True
fb77f295f754abf6a7e99a90dad5626180c5b177,PMC,Prediction of RNA Pseudoknots Using Heuristic Modeling with Mapping and Sequential Folding,http://dx.doi.org/10.1371/journal.pone.0000905,PMC1975678,17878940,CC BY,"Predicting RNA secondary structure is often the first step to determining the structure of RNA. Prediction approaches have historically avoided searching for pseudoknots because of the extreme combinatorial and time complexity of the problem. Yet neglecting pseudoknots limits the utility of such approaches. Here, an algorithm utilizing structure mapping and thermodynamics is introduced for RNA pseudoknot prediction that finds the minimum free energy and identifies information about the flexibility of the RNA. The heuristic approach takes advantage of the 5′ to 3′ folding direction of many biological RNA molecules and is consistent with the hierarchical folding hypothesis and the contact order model. Mapping methods are used to build and analyze the folded structure for pseudoknots and to add important 3D structural considerations. The program can predict some well known pseudoknot structures correctly. The results of this study suggest that many functional RNA sequences are optimized for proper folding. They also suggest directions we can proceed in the future to achieve even better results.",2007 Sep 19,"['Dawson, Wayne K.', 'Fujiwara, Kazuya', 'Kawai, Gota']",PLoS One,,,True
898be097851a56d857d6cdb8ccbbdd3666eb4963,PMC,Prediction of RNA Pseudoknots Using Heuristic Modeling with Mapping and Sequential Folding,http://dx.doi.org/10.1371/journal.pone.0000905,PMC1975678,17878940,CC BY,"Predicting RNA secondary structure is often the first step to determining the structure of RNA. Prediction approaches have historically avoided searching for pseudoknots because of the extreme combinatorial and time complexity of the problem. Yet neglecting pseudoknots limits the utility of such approaches. Here, an algorithm utilizing structure mapping and thermodynamics is introduced for RNA pseudoknot prediction that finds the minimum free energy and identifies information about the flexibility of the RNA. The heuristic approach takes advantage of the 5′ to 3′ folding direction of many biological RNA molecules and is consistent with the hierarchical folding hypothesis and the contact order model. Mapping methods are used to build and analyze the folded structure for pseudoknots and to add important 3D structural considerations. The program can predict some well known pseudoknot structures correctly. The results of this study suggest that many functional RNA sequences are optimized for proper folding. They also suggest directions we can proceed in the future to achieve even better results.",2007 Sep 19,"['Dawson, Wayne K.', 'Fujiwara, Kazuya', 'Kawai, Gota']",PLoS One,,,True
c42f08c1803b6a13e7ff20041f34d336e4b0c7e9,PMC,Identification of new reference genes for the normalisation of canine osteoarthritic joint tissue transcripts from microarray data,http://dx.doi.org/10.1186/1471-2199-8-62,PMC1976117,17651481,CC BY,"BACKGROUND: Real-time reverse transcriptase quantitative polymerase chain reaction (real-time RT-qPCR) is the most accurate measure of gene expression in biological systems. The comparison of different samples requires the transformation of data through a process called normalisation. Reference or housekeeping genes are candidate genes which are selected on the basis of constitutive expression across samples, and allow the quantification of changes in gene expression. At present, no reference gene has been identified for any organism which is universally optimal for use across different tissue types or disease situations. We used microarray data to identify new reference genes generated from total RNA isolated from normal and osteoarthritic canine articular tissues (bone, ligament, cartilage, synovium and fat). RT-qPCR assays were designed and applied to each different articular tissue. Reference gene expression stability and ranking was compared using three different mathematical algorithms. RESULTS: Twelve new potential reference genes were identified from microarray data. One gene (mitochondrial ribosomal protein S7 [MRPS7]) was stably expressed in all five of the articular tissues evaluated. One gene HIRA interacting protein 5 isoform 2 [HIRP5]) was stably expressed in four of the tissues evaluated. A commonly used reference gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was not stably expressed in any of the tissues evaluated. Most consistent agreement between rank ordering of reference genes was observed between Bestkeeper© and geNorm, although each method tended to agree on the identity of the most stably expressed genes and the least stably expressed genes for each tissue. New reference genes identified using microarray data normalised in a conventional manner were more stable than those identified by microarray data normalised by using a real-time RT-qPCR methodology. CONCLUSION: Microarray data normalised by a conventional manner can be filtered using a simple stepwise procedure to identify new reference genes, some of which will demonstrate good measures of stability. Mitochondrial ribosomal protein S7 is a new reference gene worthy of investigation in other canine tissues and diseases. Different methods of reference gene stability assessment will generally agree on the most and least stably expressed genes, when co-regulation is not present.",2007 Jul 25,"['Maccoux, Lindsey J', 'Clements, Dylan N', 'Salway, Fiona', 'Day, Philip JR']",BMC Mol Biol,,,True
753d7438fe0a32b2c68985a255f92661145d46d2,PMC,Identification of Upper Respiratory Tract Pathogens Using Electrochemical Detection on an Oligonucleotide Microarray,http://dx.doi.org/10.1371/journal.pone.0000924,PMC1976596,17895966,CC0,"Bacterial and viral upper respiratory infections (URI) produce highly variable clinical symptoms that cannot be used to identify the etiologic agent. Proper treatment, however, depends on correct identification of the pathogen involved as antibiotics provide little or no benefit with viral infections. Here we describe a rapid and sensitive genotyping assay and microarray for URI identification using standard amplification and hybridization techniques, with electrochemical detection (ECD) on a semiconductor-based oligonucleotide microarray. The assay was developed to detect four bacterial pathogens (Bordetella pertussis, Streptococcus pyogenes, Chlamydia pneumoniae and Mycoplasma pneumoniae) and 9 viral pathogens (adenovirus 4, coronavirus OC43, 229E and HK, influenza A and B, parainfluinza types 1, 2, and 3 and respiratory syncytial virus. This new platform forms the basis for a fully automated diagnostics system that is very flexible and can be customized to suit different or additional pathogens. Multiple probes on a flexible platform allow one to test probes empirically and then select highly reactive probes for further iterative evaluation. Because ECD uses an enzymatic reaction to create electrical signals that can be read directly from the array, there is no need for image analysis or for expensive and delicate optical scanning equipment. We show assay sensitivity and specificity that are excellent for a multiplexed format.",2007 Sep 26,"['Lodes, Michael J.', 'Suciu, Dominic', 'Wilmoth, Jodi L.', 'Ross, Marty', 'Munro, Sandra', 'Dix, Kim', 'Bernards, Karen', 'Stöver, Axel G.', 'Quintana, Miguel', 'Iihoshi, Naomi', 'Lyon, Wanda J.', 'Danley, David L.', 'McShea, Andrew']",PLoS One,,,True
d1f82bd6a621efe50dc1888f875c82c7d948a547,PMC,A Diverse Group of Previously Unrecognized Human Rhinoviruses Are Common Causes of Respiratory Illnesses in Infants,http://dx.doi.org/10.1371/journal.pone.0000966,PMC1989136,17912345,CC BY,"BACKGROUND: Human rhinoviruses (HRVs) are the most prevalent human pathogens, and consist of 101 serotypes that are classified into groups A and B according to sequence variations. HRV infections cause a wide spectrum of clinical outcomes ranging from asymptomatic infection to severe lower respiratory symptoms. Defining the role of specific strains in various HRV illnesses has been difficult because traditional serology, which requires viral culture and neutralization tests using 101 serotype-specific antisera, is insensitive and laborious. METHODS AND FINDINGS: To directly type HRVs in nasal secretions of infants with frequent respiratory illnesses, we developed a sensitive molecular typing assay based on phylogenetic comparisons of a 260-bp variable sequence in the 5' noncoding region with homologous sequences of the 101 known serotypes. Nasal samples from 26 infants were first tested with a multiplex PCR assay for respiratory viruses, and HRV was the most common virus found (108 of 181 samples). Typing was completed for 101 samples and 103 HRVs were identified. Surprisingly, 54 (52.4%) HRVs did not match any of the known serotypes and had 12–35% nucleotide divergence from the nearest reference HRVs. Of these novel viruses, 9 strains (17 HRVs) segregated from HRVA, HRVB and human enterovirus into a distinct genetic group (“C”). None of these new strains could be cultured in traditional cell lines. CONCLUSIONS: By molecular analysis, over 50% of HRV detected in sick infants were previously unrecognized strains, including 9 strains that may represent a new HRV group. These findings indicate that the number of HRV strains is considerably larger than the 101 serotypes identified with traditional diagnostic techniques, and provide evidence of a new HRV group.",2007 Oct 3,"['Lee, Wai-Ming', 'Kiesner, Christin', 'Pappas, Tressa', 'Lee, Iris', 'Grindle, Kris', 'Jartti, Tuomas', 'Jakiela, Bogdan', 'Lemanske, Robert F.', 'Shult, Peter A.', 'Gern, James E.']",PLoS One,,,True
a1213a37009cf0d561bdfe620cbeabf8de2778d1,PMC,Conformational Reorganization of the SARS Coronavirus Spike Following Receptor Binding: Implications for Membrane Fusion,http://dx.doi.org/10.1371/journal.pone.0001082,PMC2034598,17957264,CC BY,"The SARS coronavirus (SARS-CoV) spike is the largest known viral spike molecule, and shares a similar function with all class 1 viral fusion proteins. Previous structural studies of membrane fusion proteins have largely used crystallography of static molecular fragments, in isolation of their transmembrane domains. In this study we have produced purified, irradiated SARS-CoV virions that retain their morphology, and are fusogenic in cell culture. We used cryo-electron microscopy and image processing to investigate conformational changes that occur in the entire spike of intact virions when they bind to the viral receptor, angiotensin-converting enzyme 2 (ACE2). We have shown that ACE2 binding results in structural changes that appear to be the initial step in viral membrane fusion, and precisely localized the receptor-binding and fusion core domains within the entire spike. Furthermore, our results show that receptor binding and subsequent membrane fusion are distinct steps, and that each spike can bind up to three ACE2 molecules. The SARS-CoV spike provides an ideal model system to study receptor binding and membrane fusion in the native state, employing cryo-electron microscopy and single-particle image analysis.",2007 Oct 24,"['Beniac, Daniel R.', 'deVarennes, Shauna L.', 'Andonov, Anton', 'He, Runtao', 'Booth, Tim F.']",PLoS One,,,True
89cc8249f1595458ab949c3e6fad98dbb19a40d2,PMC,Non-pharmaceutical public health interventions for pandemic influenza: an evaluation of the evidence base,http://dx.doi.org/10.1186/1471-2458-7-208,PMC2040158,17697389,CC BY,"BACKGROUND: In an influenza pandemic, the benefit of vaccines and antiviral medications will be constrained by limitations on supplies and effectiveness. Non-pharmaceutical public health interventions will therefore be vital in curtailing disease spread. However, the most comprehensive assessments of the literature to date recognize the generally poor quality of evidence on which to base non-pharmaceutical pandemic planning decisions. In light of the need to prepare for a possible pandemic despite concerns about the poor quality of the literature, combining available evidence with expert opinion about the relative merits of non-pharmaceutical interventions for pandemic influenza may lead to a more informed and widely accepted set of recommendations. We evaluated the evidence base for non-pharmaceutical public health interventions. Then, based on the collective evidence, we identified a set of recommendations for and against interventions that are specific to both the setting in which an intervention may be used and the pandemic phase, and which can be used by policymakers to prepare for a pandemic until scientific evidence can definitively respond to planners' needs. METHODS: Building on reviews of past pandemics and recent historical inquiries, we evaluated the relative merits of non-pharmaceutical interventions by combining available evidence from the literature with qualitative and quantitative expert opinion. Specifically, we reviewed the recent scientific literature regarding the prevention of human-to-human transmission of pandemic influenza, convened a meeting of experts from multiple disciplines, and elicited expert recommendation about the use of non-pharmaceutical public health interventions in a variety of settings (healthcare facilities; community-based institutions; private households) and pandemic phases (no pandemic; no US pandemic; early localized US pandemic; advanced US pandemic). RESULTS: The literature contained a dearth of evidence on the efficacy or effectiveness of most non-pharmaceutical interventions for influenza. In an effort to inform decision-making in the absence of strong scientific evidence, the experts ultimately endorsed hand hygiene and respiratory etiquette, surveillance and case reporting, and rapid viral diagnosis in all settings and during all pandemic phases. They also encouraged patient and provider use of masks and other personal protective equipment as well as voluntary self-isolation of patients during all pandemic phases. Other non-pharmaceutical interventions including mask-use and other personal protective equipment for the general public, school and workplace closures early in an epidemic, and mandatory travel restrictions were rejected as likely to be ineffective, infeasible, or unacceptable to the public. CONCLUSION: The demand for scientific evidence on non-pharmaceutical public health interventions for influenza is pervasive, and present policy recommendations must rely heavily on expert judgment. In the absence of a definitive science base, our assessment of the evidence identified areas for further investigation as well as non-pharmaceutical public health interventions that experts believe are likely to be beneficial, feasible and widely acceptable in an influenza pandemic.",2007 Aug 15,"['Aledort, Julia E', 'Lurie, Nicole', 'Wasserman, Jeffrey', 'Bozzette, Samuel A']",BMC Public Health,,,True
1b401888b1faf175680ef5a940c16b14811c301a,PMC,Non-pharmaceutical public health interventions for pandemic influenza: an evaluation of the evidence base,http://dx.doi.org/10.1186/1471-2458-7-208,PMC2040158,17697389,CC BY,"BACKGROUND: In an influenza pandemic, the benefit of vaccines and antiviral medications will be constrained by limitations on supplies and effectiveness. Non-pharmaceutical public health interventions will therefore be vital in curtailing disease spread. However, the most comprehensive assessments of the literature to date recognize the generally poor quality of evidence on which to base non-pharmaceutical pandemic planning decisions. In light of the need to prepare for a possible pandemic despite concerns about the poor quality of the literature, combining available evidence with expert opinion about the relative merits of non-pharmaceutical interventions for pandemic influenza may lead to a more informed and widely accepted set of recommendations. We evaluated the evidence base for non-pharmaceutical public health interventions. Then, based on the collective evidence, we identified a set of recommendations for and against interventions that are specific to both the setting in which an intervention may be used and the pandemic phase, and which can be used by policymakers to prepare for a pandemic until scientific evidence can definitively respond to planners' needs. METHODS: Building on reviews of past pandemics and recent historical inquiries, we evaluated the relative merits of non-pharmaceutical interventions by combining available evidence from the literature with qualitative and quantitative expert opinion. Specifically, we reviewed the recent scientific literature regarding the prevention of human-to-human transmission of pandemic influenza, convened a meeting of experts from multiple disciplines, and elicited expert recommendation about the use of non-pharmaceutical public health interventions in a variety of settings (healthcare facilities; community-based institutions; private households) and pandemic phases (no pandemic; no US pandemic; early localized US pandemic; advanced US pandemic). RESULTS: The literature contained a dearth of evidence on the efficacy or effectiveness of most non-pharmaceutical interventions for influenza. In an effort to inform decision-making in the absence of strong scientific evidence, the experts ultimately endorsed hand hygiene and respiratory etiquette, surveillance and case reporting, and rapid viral diagnosis in all settings and during all pandemic phases. They also encouraged patient and provider use of masks and other personal protective equipment as well as voluntary self-isolation of patients during all pandemic phases. Other non-pharmaceutical interventions including mask-use and other personal protective equipment for the general public, school and workplace closures early in an epidemic, and mandatory travel restrictions were rejected as likely to be ineffective, infeasible, or unacceptable to the public. CONCLUSION: The demand for scientific evidence on non-pharmaceutical public health interventions for influenza is pervasive, and present policy recommendations must rely heavily on expert judgment. In the absence of a definitive science base, our assessment of the evidence identified areas for further investigation as well as non-pharmaceutical public health interventions that experts believe are likely to be beneficial, feasible and widely acceptable in an influenza pandemic.",2007 Aug 15,"['Aledort, Julia E', 'Lurie, Nicole', 'Wasserman, Jeffrey', 'Bozzette, Samuel A']",BMC Public Health,,,False
0bbe5dfd223ce7b53d68fb0dfc3286f5bd3fc404,PMC,Non-pharmaceutical public health interventions for pandemic influenza: an evaluation of the evidence base,http://dx.doi.org/10.1186/1471-2458-7-208,PMC2040158,17697389,CC BY,"BACKGROUND: In an influenza pandemic, the benefit of vaccines and antiviral medications will be constrained by limitations on supplies and effectiveness. Non-pharmaceutical public health interventions will therefore be vital in curtailing disease spread. However, the most comprehensive assessments of the literature to date recognize the generally poor quality of evidence on which to base non-pharmaceutical pandemic planning decisions. In light of the need to prepare for a possible pandemic despite concerns about the poor quality of the literature, combining available evidence with expert opinion about the relative merits of non-pharmaceutical interventions for pandemic influenza may lead to a more informed and widely accepted set of recommendations. We evaluated the evidence base for non-pharmaceutical public health interventions. Then, based on the collective evidence, we identified a set of recommendations for and against interventions that are specific to both the setting in which an intervention may be used and the pandemic phase, and which can be used by policymakers to prepare for a pandemic until scientific evidence can definitively respond to planners' needs. METHODS: Building on reviews of past pandemics and recent historical inquiries, we evaluated the relative merits of non-pharmaceutical interventions by combining available evidence from the literature with qualitative and quantitative expert opinion. Specifically, we reviewed the recent scientific literature regarding the prevention of human-to-human transmission of pandemic influenza, convened a meeting of experts from multiple disciplines, and elicited expert recommendation about the use of non-pharmaceutical public health interventions in a variety of settings (healthcare facilities; community-based institutions; private households) and pandemic phases (no pandemic; no US pandemic; early localized US pandemic; advanced US pandemic). RESULTS: The literature contained a dearth of evidence on the efficacy or effectiveness of most non-pharmaceutical interventions for influenza. In an effort to inform decision-making in the absence of strong scientific evidence, the experts ultimately endorsed hand hygiene and respiratory etiquette, surveillance and case reporting, and rapid viral diagnosis in all settings and during all pandemic phases. They also encouraged patient and provider use of masks and other personal protective equipment as well as voluntary self-isolation of patients during all pandemic phases. Other non-pharmaceutical interventions including mask-use and other personal protective equipment for the general public, school and workplace closures early in an epidemic, and mandatory travel restrictions were rejected as likely to be ineffective, infeasible, or unacceptable to the public. CONCLUSION: The demand for scientific evidence on non-pharmaceutical public health interventions for influenza is pervasive, and present policy recommendations must rely heavily on expert judgment. In the absence of a definitive science base, our assessment of the evidence identified areas for further investigation as well as non-pharmaceutical public health interventions that experts believe are likely to be beneficial, feasible and widely acceptable in an influenza pandemic.",2007 Aug 15,"['Aledort, Julia E', 'Lurie, Nicole', 'Wasserman, Jeffrey', 'Bozzette, Samuel A']",BMC Public Health,,,False
d4f8fcc4360079a02215dd83c280e4ff2b2363be,PMC,An evaluation of Comparative Genome Sequencing (CGS) by comparing two previously-sequenced bacterial genomes,http://dx.doi.org/10.1186/1471-2164-8-274,PMC2072959,17697331,CC BY,"BACKGROUND: With the development of new technology, it has recently become practical to resequence the genome of a bacterium after experimental manipulation. It is critical though to know the accuracy of the technique used, and to establish confidence that all of the mutations were detected. RESULTS: In order to evaluate the accuracy of genome resequencing using the microarray-based Comparative Genome Sequencing service provided by Nimblegen Systems Inc., we resequenced the E. coli strain W3110 Kohara using MG1655 as a reference, both of which have been completely sequenced using traditional sequencing methods. CGS detected 7 of 8 small sequence differences, one large deletion, and 9 of 12 IS element insertions present in W3110, but did not detect a large chromosomal inversion. In addition, we confirmed that CGS also detected 2 SNPs, one deletion and 7 IS element insertions that are not present in the genome sequence, which we attribute to changes that occurred after the creation of the W3110 lambda clone library. The false positive rate for SNPs was one per 244 Kb of genome sequence. CONCLUSION: CGS is an effective way to detect multiple mutations present in one bacterium relative to another, and while highly cost-effective, is prone to certain errors. Mutations occurring in repeated sequences or in sequences with a high degree of secondary structure may go undetected. It is also critical to follow up on regions of interest in which SNPs were not called because they often indicate deletions or IS element insertions.",2007 Aug 14,"['Herring, Christopher D', 'Palsson, Bernhard Ø']",BMC Genomics,,,True
ab1dfbe0d723b54d14e414d732fbedcd40adb021,PMC,Sharing H5N1 Viruses to Stop a Global Influenza Pandemic,http://dx.doi.org/10.1371/journal.pmed.0040330,PMC2080649,18031197,CC BY,"Indonesia's refusal to share samples of H5N1 virus with World Health Organization for most of 2007 is distressing and potentially dangerous for global public health, argue the authors.",2007 Nov 20,"['Garrett, Laurie', 'Fidler, David P']",PLoS Med,,,True
9992ffbec7c8256d057b05a858cde82d36d64ae3,PMC,Antibody-Based HIV-1 Vaccines: Recent Developments and Future Directions: A summary report from a Global HIV Vaccine Enterprise Working Group,http://dx.doi.org/10.1371/journal.pmed.0040348,PMC2100141,18052607,CC BY,The authors discuss humoral immune responses to HIV and approaches to designing vaccines that induce viral neutralizing and other potentially protective antibodies.,2007 Dec 1,"['Montefiori, David', 'Sattentau, Quentin', 'Flores, Jorge', 'Esparza, José', 'Mascola, John', None]",PLoS Med,,,True
63008713691bdb1d8eed016dbc54332f11d43739,PMC,Host Gene Expression Profiling of Dengue Virus Infection in Cell Lines and Patients,http://dx.doi.org/10.1371/journal.pntd.0000086,PMC2100376,18060089,CC BY,"BACKGROUND: Despite the seriousness of dengue-related disease, with an estimated 50–100 million cases of dengue fever and 250,000–500,000 cases of dengue hemorrhagic fever/dengue shock syndrome each year, a clear understanding of dengue pathogenesis remains elusive. Because of the lack of a disease model in animals and the complex immune interaction in dengue infection, the study of host response and immunopathogenesis is difficult. The development of genomics technology, microarray and high throughput quantitative PCR have allowed researchers to study gene expression changes on a much broader scale. We therefore used this approach to investigate the host response in dengue virus-infected cell lines and in patients developing dengue fever. METHODOLOGY/PRINCIPAL FINDINGS: Using microarray and high throughput quantitative PCR method to monitor the host response to dengue viral replication in cell line infection models and in dengue patient blood samples, we identified differentially expressed genes along three major pathways; NF-κB initiated immune responses, type I interferon (IFN) and the ubiquitin proteasome pathway. Among the most highly upregulated genes were the chemokines IP-10 and I-TAC, both ligands of the CXCR3 receptor. Increased expression of IP-10 and I-TAC in the peripheral blood of ten patients at the early onset of fever was confirmed by ELISA. A highly upregulated gene in the IFN pathway, viperin, was overexpressed in A549 cells resulting in a significant reduction in viral replication. The upregulation of genes in the ubiquitin-proteasome pathway prompted the testing of proteasome inhibitors MG-132 and ALLN, both of which reduced viral replication. CONCLUSION/SIGNIFICANCE: Unbiased gene expression analysis has identified new host genes associated with dengue infection, which we have validated in functional studies. We showed that some parts of the host response can be used as potential biomarkers for the disease while others can be used to control dengue viral replication, thus representing viable targets for drug therapy.",2007 Nov 21,"['Fink, Joshua', 'Gu, Feng', 'Ling, Ling', 'Tolfvenstam, Thomas', 'Olfat, Farzad', 'Chin, Keh Chuang', 'Aw, Pauline', 'George, Joshy', 'Kuznetsov, Vladimir A.', 'Schreiber, Mark', 'Vasudevan, Subhash G.', 'Hibberd, Martin L.']",PLoS Negl Trop Dis,,,True
0e046152bb9c537c62ed4c4616a0b627ccfc992a,PMC,Rapid generation of an anthrax immunotherapeutic from goats using a novel non-toxic muramyl dipeptide adjuvant,http://dx.doi.org/10.1186/1476-8518-5-11,PMC2104530,17953756,CC BY,"BACKGROUND: There is a clear need for vaccines and therapeutics for potential biological weapons of mass destruction and emerging diseases. Anthrax, caused by the bacterium Bacillus anthracis, has been used as both a biological warfare agent and bioterrorist weapon previously. Although antibiotic therapy is effective in the early stages of anthrax infection, it does not have any effect once exposed individuals become symptomatic due to B. anthracis exotoxin accumulation. The bipartite exotoxins are the major contributing factors to the morbidity and mortality observed in acute anthrax infections. METHODS: Using recombinant B. anthracis protective antigen (PA83), covalently coupled to a novel non-toxic muramyl dipeptide (NT-MDP) derivative we hyper-immunized goats three times over the course of 14 weeks. Goats were plasmapheresed and the IgG fraction (not affinity purified) and F(ab')(2 )derivatives were characterized in vitro and in vivo for protection against lethal toxin mediated intoxication. RESULTS: Anti-PA83 IgG conferred 100% protection at 7.5 μg in a cell toxin neutralization assay. Mice exposed to 5 LD(50 )of Bacillus anthracis Ames spores by intranares inoculation demonstrated 60% survival 14 d post-infection when administered a single bolus dose (32 mg/kg body weight) of anti-PA83 IgG at 24 h post spore challenge. Anti-PA83 F(ab')(2 )fragments retained similar neutralization and protection levels both in vitro and in vivo. CONCLUSION: The protection afforded by these GMP-grade caprine immunotherapeutics post-exposure in the pilot murine model suggests they could be used effectively to treat post-exposure, symptomatic human anthrax patients following a bioterrorism event. These results also indicate that recombinant PA83 coupled to NT-MDP is a potent inducer of neutralizing antibodies and suggest it would be a promising vaccine candidate for anthrax. The ease of production, ease of covalent attachment, and immunostimulatory activity of the NT-MDP indicate it would be a superior adjuvant to alum or other traditional adjuvants in vaccine formulations.",2007 Oct 22,"['Kelly, Cassandra D', ""O'Loughlin, Chris"", 'Gelder, Frank B', 'Peterson, Johnny W', 'Sower, Laurie E', 'Cirino, Nick M']",J Immune Based Ther Vaccines,,,True
6a0f0170d5ad8bb5c0f2af642c0fc37e48dbd3a4,PMC,Species-specific evolution of immune receptor tyrosine based activation motif-containing CEACAM1-related immune receptors in the dog,http://dx.doi.org/10.1186/1471-2148-7-196,PMC2110893,17945019,CC BY,"BACKGROUND: Although the impact of pathogens on the evolution of the mammalian immune system is still under debate, proteins, which both regulate immune responses and serve as cellular receptors for pathogens should be at the forefront of pathogen-driven host evolution. The CEA (carcinoembryonic antigen) gene family codes for such proteins and indeed shows tremendous species-specific variation between human and rodents. Since little is known about the CEA gene family in other lineages of placental mammals, we expected to gain new insights into the evolution of the rapidly diverging CEA family by analyzing the CEA family of the dog. RESULTS: Here we describe the complete CEA gene family in the dog. We found that the gene coding for the ITIM-bearing immunoregulatory molecule CEACAM1 gave rise to a recent expansion of the canine CEA gene family by gene duplication, similar to that previously found in humans and mice. However, while the murine and human CEACAMs (carcinoembryonic antigen-related cell adhesion molecules) are predominantly secreted and GPI-anchored, respectively, in the dog, most of the CEACAMs represent ITAM-bearing transmembrane proteins. One of these proteins, CEACAM28, exhibits nearly complete sequence identity with the ligand-binding N domain of CEACAM1, but antagonizing signaling motifs in the cytoplasmic tail. Comparison of nonsynonymous and synonymous substitutions indicates that the CEACAM28 N domain is under the strongest purifying selection of all canine CEACAM1-related CEACAMs. In addition, CEACAM28 shows a similar expression pattern in resting immune cells and tissues as CEACAM1. However, upon activation CEACAM28 mRNA and CEACAM1 mRNA are differentially regulated. CONCLUSION: Thus, CEACAM1 and CEACAM28 are the first paired immune receptors identified within the CEA gene family, which are expressed on T cells and are most likely involved in the fine-tuning of T cell responses. The direction of gene conversion accompanied by purifying selection and expression in immune cells suggests the possibility that CEACAM28 evolved in response to selective pressure imposed by species-specific pathogens.",2007 Oct 18,"['Kammerer, Robert', 'Popp, Tanja', 'Härtle, Stefan', 'Singer, Bernhard B', 'Zimmermann, Wolfgang']",BMC Evol Biol,,,True
296e24d0dc3c17633eeffea57bd23e968a1c8a5e,PMC,Elevated adipogenesis of marrow mesenchymal stem cells during early steroid-associated osteonecrosis development,http://dx.doi.org/10.1186/1749-799X-2-15,PMC2146995,17937789,CC BY,"BACKGROUND: Increased bone marrow lipid deposition in steroid-associated osteonecrosis (ON) implies that abnormalities in fat metabolism play an important role in ON development. The increase in lipid deposition might be explained by elevated adipogenesis of marrow mesenchymal stem cells (MSCs). However, it remains unclear whether there is a close association between elevated adipogenesis and steroid-associated ON development. OBJECTIVE: The present study was designed to test the hypothesis that there might be a close association between elevated adipogenesis and steroid-associated ON development. METHODS: ON rabbit model was induced based on our established protocol. Dynamic-MRI was employed for local intra-osseous perfusion evaluation in bilateral femora. Two weeks after induction, bone marrow was harvested for evaluating the ability of adipogenic differentiation of marrow MSCs at both cellular and mRNA level involving adipogenesis-related gene peroxisome proliferator-activated receptor gamma2 (PPARγ2). The bilateral femora were dissected for examining marrow lipid deposition by quantifying fat cell number, fat cell size, lipid deposition area and ON lesions. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON occurrence, the rabbits were divided into ON(+ )(with at least one ON lesion) group and ON(- )(without ON lesion) group. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON extension, the ON(+ )rabbits were further divided into sub-single-lesion group (SON group: with one ON lesion) and sub-multiple-lesion group (MON group: with more than one ON lesion). RESULTS: Local intra-osseous perfusion index was found lower in either ON(+ )or MON group when compared to either ON(- )or SON group, whereas the marrow fat cells number and area were much larger in either ON(+ )or MON group as compared with ON(- )and SON group. The adipogenic differentiation ability of MSCs and PPARγ2 expression in either ON(+ )or MON group were elevated significantly as compared with either ON(- )or SON group. CONCLUSION: These findings support our hypothesis that there is a close association between elevated adipogenesis and steroid-associated osteonecrosis development.",2007 Oct 15,"['Sheng, Hui H', 'Zhang, Ge G', 'Cheung, Wing Hoi WH', 'Chan, Chun Wai CW', 'Wang, Yi Xiang YX', 'Lee, Kwong Man KM', 'Wang, Hong Fu HF', 'Leung, Kwok Sui KS', 'Qin, Ling L']",J Orthop Surg,,,True
e45d3e45dd952470cbbac928b949fc6339e3ec81,PMC,Saccharomyces cerevisiae: a versatile eukaryotic system in virology,http://dx.doi.org/10.1186/1475-2859-6-32,PMC2148055,17927824,CC BY,"The yeast Saccharomyces cerevisiae is a well-established model system for understanding fundamental cellular processes relevant to higher eukaryotic organisms. Less known is its value for virus research, an area in which Saccharomyces cerevisiae has proven to be very fruitful as well. The present review will discuss the main achievements of yeast-based studies in basic and applied virus research. These include the analysis of the function of individual proteins from important pathogenic viruses, the elucidation of key processes in viral replication through the development of systems that allow the replication of higher eukayotic viruses in yeast, and the use of yeast in antiviral drug development and vaccine production.",2007 Oct 10,"['Galao, Rui P', 'Scheller, Nicoletta', 'Alves-Rodrigues, Isabel', 'Breinig, Tanja', 'Meyerhans, Andreas', 'Díez, Juana']",Microb Cell Fact,,,True
2c5d1ebec404ad8061eb81e94effbe52a6dbe809,PMC,Receptor-Induced Thiolate Couples Env Activation to Retrovirus Fusion and Infection,http://dx.doi.org/10.1371/journal.ppat.0030198,PMC2151085,18260686,CC BY,"According to current models of retrovirus infection, receptor binding to the surface subunit (SU) of the envelope glycoprotein (Env) triggers a conformational change in the transmembrane subunit (TM) that mediates virus fusion to cell membranes. To understand how this occurs, we investigated the role of the receptor Tva in avian leukosis virus-A (ALV-A) infection. We find that Tva binding induced the formation of a reactive thiolate on Cys38 (Cys38-S(−)) in SU. Both chemical and genetic inactivation of Cys38-S(−) completely abrogated ALV fusion and infection. Remarkably, Cys38-S(−) does not mediate isomerization of the SU-TM disulfide bond and is not required for Tva-induced activation of TM, including pre-hairpin association with membranes and low pH assembly of helical bundles. These findings indicate that, contrary to current models, receptor activation of TM is not sufficient for ALV fusion and infection and that formation of a reactive thiolate is an additional receptor-dependent step.",2007 Dec 21,"['Smith, Jason G', 'Cunningham, James M']",PLoS Pathog,,,True
8a18be6bbec92094276f843c39fa9ea509e20215,PMC,"Plague: Past, Present, and Future",http://dx.doi.org/10.1371/journal.pmed.0050003,PMC2194748,18198939,CC0,The authors argue that plague should be taken much more seriously by the international health community.,2008 Jan 15,"['Stenseth, Nils Chr', 'Atshabar, Bakyt B', 'Begon, Mike', 'Belmain, Steven R', 'Bertherat, Eric', 'Carniel, Elisabeth', 'Gage, Kenneth L', 'Leirs, Herwig', 'Rahalison, Lila']",PLoS Med,,,True
7a0851e43f82ced2223468ad1280a914fed947b2,PMC,"Plague: Past, Present, and Future",http://dx.doi.org/10.1371/journal.pmed.0050003,PMC2194748,18198939,CC0,The authors argue that plague should be taken much more seriously by the international health community.,2008 Jan 15,"['Stenseth, Nils Chr', 'Atshabar, Bakyt B', 'Begon, Mike', 'Belmain, Steven R', 'Bertherat, Eric', 'Carniel, Elisabeth', 'Gage, Kenneth L', 'Leirs, Herwig', 'Rahalison, Lila']",PLoS Med,,,True
99da41d8c3a3aebdaf5d889c3958181ae52ff6a9,PMC,"Plague: Past, Present, and Future",http://dx.doi.org/10.1371/journal.pmed.0050003,PMC2194748,18198939,CC0,The authors argue that plague should be taken much more seriously by the international health community.,2008 Jan 15,"['Stenseth, Nils Chr', 'Atshabar, Bakyt B', 'Begon, Mike', 'Belmain, Steven R', 'Bertherat, Eric', 'Carniel, Elisabeth', 'Gage, Kenneth L', 'Leirs, Herwig', 'Rahalison, Lila']",PLoS Med,,,True
139b81bc9c99d76cffc2014c4851942d2f592950,PMC,Modeling and detection of respiratory-related outbreak signatures,http://dx.doi.org/10.1186/1472-6947-7-28,PMC2203979,17919318,CC BY,"BACKGROUND: Time series methods are commonly used to detect disease outbreak signatures (e.g., signals due to influenza outbreaks and anthrax attacks) from varying respiratory-related diagnostic or syndromic data sources. Typically this involves two components: (i) Using time series methods to model the baseline background distribution (the time series process that is assumed to contain no outbreak signatures), (ii) Detecting outbreak signatures using filter-based time series methods. METHODS: We consider time series models for chest radiograph data obtained from Midwest children's emergency departments. These models incorporate available covariate information such as patient visit counts and smoothed ambient temperature series, as well as time series dependencies on daily and weekly seasonal scales. Respiratory-related outbreak signature detection is based on filtering the one-step-ahead prediction errors obtained from the time series models for the respiratory-complaint background. RESULTS: Using simulation experiments based on a stochastic model for an anthrax attack, we illustrate the effect of the choice of filter and the statistical models upon radiograph-attributed outbreak signature detection. CONCLUSION: We demonstrate the importance of using seasonal autoregressive integrated average time series models (SARIMA) with covariates in the modeling of respiratory-related time series data. We find some homogeneity in the time series models for the respiratory-complaint backgrounds across the Midwest emergency departments studied. Our simulations show that the balance between specificity, sensitivity, and timeliness to detect an outbreak signature differs by the emergency department and the choice of filter. The linear and exponential filters provide a good balance.",2007 Oct 5,"['Craigmile, Peter F', 'Kim, Namhee', 'Fernandez, Soledad A', 'Bonsu, Bema K']",BMC Med Inform Decis Mak,,,True
8d355f050721e1e9d9288c7824cc38546b6ef2a6,PMC,The costs of preventing the spread of respiratory infection in family physician offices: a threshold analysis,http://dx.doi.org/10.1186/1472-6963-7-181,PMC2204002,17999757,CC BY,"BACKGROUND: Influenza poses concerns about epidemic respiratory infection. Interventions designed to prevent the spread of respiratory infection within family physician (FP) offices could potentially have a significant positive influence on the health of Canadians. The main purpose of this paper is to estimate the explicit costs of such an intervention. METHODS: A cost analysis of a respiratory infection control was conducted. The costs were estimated from the perspective of provincial government. In addition, a threshold analysis was conducted to estimate a threshold value of the intervention's effectiveness that could generate potential savings in terms of averted health-care costs by the intervention that exceed the explicit costs. The informational requirements for these implicit costs savings are high, however. Some of these elements, such as the cost of hospitalization in the event of contacting influenza, and the number of patients passing through the physicians' office, were readily available. Other pertinent points of information, such as the proportion of infected people who require hospitalization, could be imported from the existing literature. We take an indirect approach to calculate a threshold value for the most uncertain piece of information, namely the reduction in the probability of the infection spreading as a direct result of the intervention, at which the intervention becomes worthwhile. RESULTS: The 5-week intervention costs amounted to a total of $52,810.71, or $131,094.73 prorated according to the length of the flu season, or $512,729.30 prorated for the entire calendar year. The variable costs that were incurred for this 5-week project amounted to approximately $923.16 per participating medical practice. The (fixed) training costs per practice were equivalent to $73.27 for the 5-week intervention, or $28.14 for 13-week flu season, or $7.05 for an entire one-year period. CONCLUSION: Based on our conservative estimates for the direct cost savings, there are indications that the outreach facilitation intervention program would be cost effective if it can achieve a reduction in the probability of infection on the order of 0.83 (0.77, 1.05) percentage points. A facilitation intervention initiative tailored to the environment and needs of the family medical practice and walk-in clinics is of promise for improving respiratory infection control in the physicians' offices.",2007 Nov 13,"['Hogg, William', 'Gray, David', 'Huston, Patricia', 'Zhang, Wei']",BMC Health Serv Res,,,True
26b43aa70c7a8314456956b5ada051dc6807dc56,PMC,Optimal design and validation of antiviral siRNA for targeting HIV-1,http://dx.doi.org/10.1186/1742-4690-4-80,PMC2204037,17996047,CC BY,"We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.",2007 Nov 8,"['Naito, Yuki', 'Nohtomi, Kyoko', 'Onogi, Toshinari', 'Uenishi, Rie', 'Ui-Tei, Kumiko', 'Saigo, Kaoru', 'Takebe, Yutaka']",Retrovirology,,,True
69f030af7402d525617886c4ab8a9bbe413c01c0,PMC,Optimal design and validation of antiviral siRNA for targeting HIV-1,http://dx.doi.org/10.1186/1742-4690-4-80,PMC2204037,17996047,CC BY,"We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.",2007 Nov 8,"['Naito, Yuki', 'Nohtomi, Kyoko', 'Onogi, Toshinari', 'Uenishi, Rie', 'Ui-Tei, Kumiko', 'Saigo, Kaoru', 'Takebe, Yutaka']",Retrovirology,,,False
05a3101918abeee449871529fb0b788dd90df479,PMC,Optimal design and validation of antiviral siRNA for targeting HIV-1,http://dx.doi.org/10.1186/1742-4690-4-80,PMC2204037,17996047,CC BY,"We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.",2007 Nov 8,"['Naito, Yuki', 'Nohtomi, Kyoko', 'Onogi, Toshinari', 'Uenishi, Rie', 'Ui-Tei, Kumiko', 'Saigo, Kaoru', 'Takebe, Yutaka']",Retrovirology,,,True
5978486a06f337a76f6dda4dec594be3fac4d646,PMC,Optimal design and validation of antiviral siRNA for targeting HIV-1,http://dx.doi.org/10.1186/1742-4690-4-80,PMC2204037,17996047,CC BY,"We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.",2007 Nov 8,"['Naito, Yuki', 'Nohtomi, Kyoko', 'Onogi, Toshinari', 'Uenishi, Rie', 'Ui-Tei, Kumiko', 'Saigo, Kaoru', 'Takebe, Yutaka']",Retrovirology,,,False
4b88c761100af90fc95bc20644cbf9dda06febb1,PMC,Optimal design and validation of antiviral siRNA for targeting HIV-1,http://dx.doi.org/10.1186/1742-4690-4-80,PMC2204037,17996047,CC BY,"We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.",2007 Nov 8,"['Naito, Yuki', 'Nohtomi, Kyoko', 'Onogi, Toshinari', 'Uenishi, Rie', 'Ui-Tei, Kumiko', 'Saigo, Kaoru', 'Takebe, Yutaka']",Retrovirology,,,False
a24f5d43a265d352f8aafdde4d2f7369ff4d49d5,PMC,Optimal design and validation of antiviral siRNA for targeting HIV-1,http://dx.doi.org/10.1186/1742-4690-4-80,PMC2204037,17996047,CC BY,"We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.",2007 Nov 8,"['Naito, Yuki', 'Nohtomi, Kyoko', 'Onogi, Toshinari', 'Uenishi, Rie', 'Ui-Tei, Kumiko', 'Saigo, Kaoru', 'Takebe, Yutaka']",Retrovirology,,,False
f83cf1bf40760964918e556f51bf628891da95e5,PMC,Optimal design and validation of antiviral siRNA for targeting HIV-1,http://dx.doi.org/10.1186/1742-4690-4-80,PMC2204037,17996047,CC BY,"We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.",2007 Nov 8,"['Naito, Yuki', 'Nohtomi, Kyoko', 'Onogi, Toshinari', 'Uenishi, Rie', 'Ui-Tei, Kumiko', 'Saigo, Kaoru', 'Takebe, Yutaka']",Retrovirology,,,False
28e3c0e0e0dbbf0d60f6033ef5254c5ccf138b37,PMC,Optimal design and validation of antiviral siRNA for targeting HIV-1,http://dx.doi.org/10.1186/1742-4690-4-80,PMC2204037,17996047,CC BY,"We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.",2007 Nov 8,"['Naito, Yuki', 'Nohtomi, Kyoko', 'Onogi, Toshinari', 'Uenishi, Rie', 'Ui-Tei, Kumiko', 'Saigo, Kaoru', 'Takebe, Yutaka']",Retrovirology,,,False
5abea4a5497c9cfa476bf766b8360f73c12e8122,PMC,Coronavirus Spike Protein Inhibits Host Cell Translation by Interaction with eIF3f,http://dx.doi.org/10.1371/journal.pone.0001494,PMC2204050,18231581,CC BY,"In response to viral infection, the expression of numerous host genes, including predominantly a number of proinflammatory cytokines and chemokines, is usually up-regulated at both transcriptional and translational levels. It was noted that in cells infected with coronavirus, transcription and translation of some of these genes were differentially induced. Drastic induction of their expression at the transcriptional level was observed in cells infected with coronavirus. However, induction of the same genes at the translational level was usually found to be minimal to moderate. To investigate the underlying mechanisms, yeast two-hybrid screen was carried out using SARS-CoV proteins as baits, revealing that a subunit of the eukaryotic initiation factor 3 (eIF3), eIF3f, may interact with the N-terminal region of the SARS-CoV spike (S) protein. This interaction was subsequently confirmed by co-immunoprecipitation and immunofluorescent staining. Meanwhile, parallel experiments confirmed that eIF3f could also interact with the S protein of another coronavirus, the avian coronavirus infectious bronchitis virus (IBV). These interactions led to the inhibition of translation of a reporter gene in both in vitro expression system and intact cells. Interestingly, IBV-infected cells stably expressing a Flag-tagged eIF3f showed much higher translation of IL-6 and IL-8, suggesting that the interaction between coronavirus S protein and eIF3f plays a functional role in controlling the expression of host genes, especially genes that are induced during coronavirus infection cycles. This study reveals a novel mechanism exploited by coronavirus to regulate viral pathogenesis.",2008 Jan 30,"['Xiao, Han', 'Xu, Ling Hui', 'Yamada, Yoshiyuki', 'Liu, Ding Xiang']",PLoS One,,,True
16ffa1f7efaf96880e6f3c22d2de9c5672169303,PMC,Transmissibility of the Influenza Virus in the 1918 Pandemic,http://dx.doi.org/10.1371/journal.pone.0001498,PMC2204055,18231585,CC BY,"BACKGROUND: With a heightened increase in concern for an influenza pandemic we sought to better understand the 1918 Influenza pandemic, the most devastating epidemic of the previous century. METHODOLOGY/PRINCIPAL FINDINGS: We use data from several communities in Maryland, USA as well as two ships that experienced well-documented outbreaks of influenza in 1918. Using a likelihood-based method and a nonparametric method, we estimate the serial interval and reproductive number throughout the course of each outbreak. This analysis shows the basic reproductive number to be slightly lower in the Maryland communities (between 1.34 and 3.21) than for the enclosed populations on the ships (R(0) = 4.97, SE = 3.31). Additionally the effective reproductive number declined to sub epidemic levels more quickly on the ships (within around 10 days) than in the communities (within 30–40 days). The mean serial interval for the ships was consistent (3.33, SE = 5.96 and 3.81, SE = 3.69), while the serial intervals in the communities varied substantially (between 2.83, SE = 0.53 and 8.28, SE = 951.95). CONCLUSIONS/SIGNIFICANCE: These results illustrate the importance of considering the population dynamics when making statements about the epidemiological parameters of Influenza. The methods that we employ for estimation of the reproductive numbers and the serial interval can be easily replicated in other populations and with other diseases.",2008 Jan 30,"['White, Laura Forsberg', 'Pagano, Marcello']",PLoS One,,,True
c899a0907dc026208ece3df9c6d4b3c909c6dd46,PMC,"Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study",http://dx.doi.org/10.1186/cc5723,PMC2206456,17362525,CC BY,"INTRODUCTION: Accurate and timely diagnosis of community-acquired bacterial infections in patients with systemic inflammation remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis and thereby survival. We therefore compared the diagnostic characteristics of novel and routinely used biomarkers of sepsis alone and in combination. METHODS: This prospective cohort study included patients with systemic inflammatory response syndrome who were suspected of having community-acquired infections. It was conducted in a medical emergency department and department of infectious diseases at a university hospital. A multiplex immunoassay measuring soluble urokinase-type plasminogen activator (suPAR) and soluble triggering receptor expressed on myeloid cells (sTREM)-1 and macrophage migration inhibitory factor (MIF) was used in parallel with standard measurements of C-reactive protein (CRP), procalcitonin (PCT), and neutrophils. Two composite markers were constructed – one including a linear combination of the three best performing markers and another including all six – and the area under the receiver operating characteristic curve (AUC) was used to compare their performance and those of the individual markers. RESULTS: A total of 151 patients were eligible for analysis. Of these, 96 had bacterial infections. The AUCs for detection of a bacterial cause of inflammation were 0.50 (95% confidence interval [CI] 0.40 to 0.60) for suPAR, 0.61 (95% CI 0.52 to 0.71) for sTREM-1, 0.63 (95% CI 0.53 to 0.72) for MIF, 0.72 (95% CI 0.63 to 0.79) for PCT, 0.74 (95% CI 0.66 to 0.81) for neutrophil count, 0.81 (95% CI 0.73 to 0.86) for CRP, 0.84 (95% CI 0.71 to 0.91) for the composite three-marker test, and 0.88 (95% CI 0.81 to 0.92) for the composite six-marker test. The AUC of the six-marker test was significantly greater than that of the single markers. CONCLUSION: Combining information from several markers improves diagnostic accuracy in detecting bacterial versus nonbacterial causes of inflammation. Measurements of suPAR, sTREM-1 and MIF had limited value as single markers, whereas PCT and CRP exhibited acceptable diagnostic characteristics. TRIAL REGISTRATION: NCT 00389337",2007 Mar 16,"['Kofoed, Kristian', 'Andersen, Ove', 'Kronborg, Gitte', 'Tvede, Michael', 'Petersen, Janne', 'Eugen-Olsen, Jesper', 'Larsen, Klaus']",Crit Care,,,True
e035002c8135dab46801a3fc8a43b87240dbef8d,PMC,Predictability and epidemic pathways in global outbreaks of infectious diseases: the SARS case study,http://dx.doi.org/10.1186/1741-7015-5-34,PMC2213648,18031574,CC BY,"BACKGROUND: The global spread of the severe acute respiratory syndrome (SARS) epidemic has clearly shown the importance of considering the long-range transportation networks in the understanding of emerging diseases outbreaks. The introduction of extensive transportation data sets is therefore an important step in order to develop epidemic models endowed with realism. METHODS: We develop a general stochastic meta-population model that incorporates actual travel and census data among 3 100 urban areas in 220 countries. The model allows probabilistic predictions on the likelihood of country outbreaks and their magnitude. The level of predictability offered by the model can be quantitatively analyzed and related to the appearance of robust epidemic pathways that represent the most probable routes for the spread of the disease. RESULTS: In order to assess the predictive power of the model, the case study of the global spread of SARS is considered. The disease parameter values and initial conditions used in the model are evaluated from empirical data for Hong Kong. The outbreak likelihood for specific countries is evaluated along with the emerging epidemic pathways. Simulation results are in agreement with the empirical data of the SARS worldwide epidemic. CONCLUSION: The presented computational approach shows that the integration of long-range mobility and demographic data provides epidemic models with a predictive power that can be consistently tested and theoretically motivated. This computational strategy can be therefore considered as a general tool in the analysis and forecast of the global spreading of emerging diseases and in the definition of containment policies aimed at reducing the effects of potentially catastrophic outbreaks.",2007 Nov 21,"['Colizza, Vittoria', 'Barrat, Alain', 'Barthélemy, Marc', 'Vespignani, Alessandro']",BMC Med,,,True
59f7edc22693dec7a22ed949597d2bbc06002325,PMC,Predictability and epidemic pathways in global outbreaks of infectious diseases: the SARS case study,http://dx.doi.org/10.1186/1741-7015-5-34,PMC2213648,18031574,CC BY,"BACKGROUND: The global spread of the severe acute respiratory syndrome (SARS) epidemic has clearly shown the importance of considering the long-range transportation networks in the understanding of emerging diseases outbreaks. The introduction of extensive transportation data sets is therefore an important step in order to develop epidemic models endowed with realism. METHODS: We develop a general stochastic meta-population model that incorporates actual travel and census data among 3 100 urban areas in 220 countries. The model allows probabilistic predictions on the likelihood of country outbreaks and their magnitude. The level of predictability offered by the model can be quantitatively analyzed and related to the appearance of robust epidemic pathways that represent the most probable routes for the spread of the disease. RESULTS: In order to assess the predictive power of the model, the case study of the global spread of SARS is considered. The disease parameter values and initial conditions used in the model are evaluated from empirical data for Hong Kong. The outbreak likelihood for specific countries is evaluated along with the emerging epidemic pathways. Simulation results are in agreement with the empirical data of the SARS worldwide epidemic. CONCLUSION: The presented computational approach shows that the integration of long-range mobility and demographic data provides epidemic models with a predictive power that can be consistently tested and theoretically motivated. This computational strategy can be therefore considered as a general tool in the analysis and forecast of the global spreading of emerging diseases and in the definition of containment policies aimed at reducing the effects of potentially catastrophic outbreaks.",2007 Nov 21,"['Colizza, Vittoria', 'Barrat, Alain', 'Barthélemy, Marc', 'Vespignani, Alessandro']",BMC Med,,,False
910f8cb2d8f7ceb37d996bcbf327b4f5b26ed6d5,PMC,Determination of suitable housekeeping genes for normalisation of quantitative real time PCR analysis of cells infected with human immunodeficiency virus and herpes viruses,http://dx.doi.org/10.1186/1743-422X-4-130,PMC2216015,18053162,CC BY,"The choice of an appropriate housekeeping gene for normalisation purposes has now become an essential requirement when designing QPCR experiments. This is of particular importance when using QPCR to measure viral and cellular gene transcription levels in the context of viral infections as viruses can significantly interfere with host cell pathways, the components of which traditional housekeeping genes often encode. In this study we have determined the reliability of 10 housekeeping genes in context of four heavily studied viral infections; human immunodeficiency virus type 1, herpes simplex virus type 1, cytomegalovirus and varicella zoster virus infections using a variety of cell types and virus strains. This provides researchers of these viruses with a shortlist of potential housekeeping genes to use as normalisers for QPCR experiments.",2007 Dec 3,"['Watson, Sarah', 'Mercier, Sarah', 'Bye, Chris', 'Wilkinson, John', 'Cunningham, Anthony L', 'Harman, Andrew N']",Virol J,,,True
ab1f467d067233119dcffc5c542a88cbd7794397,PMC,"C-ME: A 3D Community-Based, Real-Time Collaboration Tool for Scientific Research and Training",http://dx.doi.org/10.1371/journal.pone.0001621,PMC2229842,18286178,CC BY,"The need for effective collaboration tools is growing as multidisciplinary proteome-wide projects and distributed research teams become more common. The resulting data is often quite disparate, stored in separate locations, and not contextually related. Collaborative Molecular Modeling Environment (C-ME) is an interactive community-based collaboration system that allows researchers to organize information, visualize data on a two-dimensional (2-D) or three-dimensional (3-D) basis, and share and manage that information with collaborators in real time. C-ME stores the information in industry-standard databases that are immediately accessible by appropriate permission within the computer network directory service or anonymously across the internet through the C-ME application or through a web browser. The system addresses two important aspects of collaboration: context and information management. C-ME allows a researcher to use a 3-D atomic structure model or a 2-D image as a contextual basis on which to attach and share annotations to specific atoms or molecules or to specific regions of a 2-D image. These annotations provide additional information about the atomic structure or image data that can then be evaluated, amended or added to by other project members.",2008 Feb 20,"['Kolatkar, Anand', 'Kennedy, Kevin', 'Halabuk, Dan', 'Kunken, Josh', 'Marrinucci, Dena', 'Bethel, Kelly', 'Guzman, Rodney', 'Huckaby, Tim', 'Kuhn, Peter']",PLoS One,,,True
7d7dbaff8c306dacea117552f6c97cb0b2b79ce3,PMC,Leptospirosis vaccines,http://dx.doi.org/10.1186/1475-2859-6-39,PMC2231387,18072968,CC BY,"Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP) vaccines, lipopolysaccharide (LPS) vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool.",2007 Dec 11,"['Wang, Zhijun', 'Jin, Li', 'Węgrzyn, Alicja']",Microb Cell Fact,,,True
9d0ae9643da1b47c2234dd758a36ed3c3abc1aa2,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,True
cc724dd07268172a4d5b9d83df29fe32757dee98,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,True
0ed28158b9c944a36a22e6bb70ced547b0755ce3,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
8af5e1ddf29c2597dc841ca2d98f66947c232efb,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
4fbdae4fb7137b1db67c84619a04c7e4450a99fc,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
edbbf63540091284b702964a7c675bed500ec6ff,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
00ab80b71e43170669f4d5e762e102955e8e65d2,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
45897239ea14ad999550f9658168e4c59f7a64c8,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
5745f2adfd8f187f6d80ff4b6107e4c98c4fdade,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
1c189a9d2d493dff4bc906c03d5543dd7569d85d,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
0fc2fd4157d793fbcbb1b155c62f6e051a629b2d,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
368f95b18acbb5d7ac2c3fc58a2256e356b14212,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
35446cde6846ab1bf25e5e4db69ef202ac2e6043,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
452bccd188bdb4d74dafecdb234f031d822b084c,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
a7b6a9784c14b8fd02756ceaeb5c722095ae40be,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
fe2946af76126343fa6398ee9101da1b84f75a24,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
f0af5c3c75acfecfb4f50efe03b16cd3fced7b80,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
7d18def448c40e3f7a9e1875ed3a641306c95b00,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
a5edf71b28d875a8c2761850356e0ed5b62e3265,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
44f3796bf7bdaa361b977d350bc71190b31cf558,PMC,Analysis and prediction of protective continuous B-cell epitopes on pathogen proteins,http://dx.doi.org/10.1186/1745-7580-4-1,PMC2244602,18179690,CC BY,"BACKGROUND: The application of peptide based diagnostics and therapeutics mimicking part of protein antigen is experiencing renewed interest. So far selection and design rationale for such peptides is usually driven by T-cell epitope prediction, available experimental and modelled 3D structure, B-cell epitope predictions such as hydrophilicity plots or experience. If no structure is available the rational selection of peptides for the production of functionally altering or neutralizing antibodies is practically impossible. Specifically if many alternative antigens are available the reduction of required synthesized peptides until one successful candidate is found is of central technical interest. We have investigated the integration of B-cell epitope prediction with the variability of antigen and the conservation of patterns for post-translational modification (PTM) prediction to improve over state of the art in the field. In particular the application of machine-learning methods shows promising results. RESULTS: We find that protein regions leading to the production of functionally altering antibodies are often characterized by a distinct increase in the cumulative sum of three presented parameters. Furthermore the concept to maximize antigenicity, minimize variability and minimize the likelihood of post-translational modification for the identification of relevant sites leads to biologically interesting observations. Primarily, for about 50% of antigen the approach works well with individual area under the ROC curve (AROC) values of at least 0.65. On the other hand a significant portion reveals equivalently low AROC values of < = 0.35 indicating an overall non-Gaussian distribution. While about a third of 57 antigens are seemingly intangible by our approach our results suggest the existence of at least two distinct classes of bioinformatically detectable epitopes which should be predicted separately. As a side effect of our study we present a hand curated dataset for the validation of protectivity classification. Based on this dataset machine-learning methods further improve predictive power to a class separation in an equilibrated dataset of up to 83%. CONCLUSION: We present a computational method to automatically select and rank peptides for the stimulation of potentially protective or otherwise functionally altering antibodies. It can be shown that integration of variability, post-translational modification pattern conservation and B-cell antigenicity improve rational selection over random guessing. Probably more important, we find that for about 50% of antigen the approach works substantially better than for the overall dataset of 57 proteins. Essentially as a side effect our method optimizes for presumably best applicable peptides as they tend to be likely unmodified and as invariable as possible which is answering needs in diagnosis and treatment of pathogen infection. In addition we show the potential for further improvement by the application of machine-learning methods, in particular Random Forests.",2008 Jan 7,"['Sollner, Johannes', 'Grohmann, Rainer', 'Rapberger, Ronald', 'Perco, Paul', 'Lukas, Arno', 'Mayer, Bernd']",Immunome Res,,,True
98b07ff87d658b09a3284a78b88ebe5687475d5a,PMC,HLA class I supertypes: a revised and updated classification,http://dx.doi.org/10.1186/1471-2172-9-1,PMC2245908,18211710,CC BY,"BACKGROUND: Class I major histocompatibility complex (MHC) molecules bind, and present to T cells, short peptides derived from intracellular processing of proteins. The peptide repertoire of a specific molecule is to a large extent determined by the molecular structure accommodating so-called main anchor positions of the presented peptide. These receptors are extremely polymorphic, and much of the polymorphism influences the peptide-binding repertoire. However, despite this polymorphism, class I molecules can be clustered into sets of molecules that bind largely overlapping peptide repertoires. Almost a decade ago we introduced this concept of clustering human leukocyte antigen (HLA) alleles and defined nine different groups, denominated as supertypes, on the basis of their main anchor specificity. The utility of this original supertype classification, as well several other subsequent arrangements derived by others, has been demonstrated in a large number of epitope identification studies. RESULTS: Following our original approach, in the present report we provide an updated classification of HLA-A and -B class I alleles into supertypes. The present analysis incorporates the large amount of class I MHC binding data and sequence information that has become available in the last decade. As a result, over 80% of the 945 different HLA-A and -B alleles examined to date can be assigned to one of the original nine supertypes. A few alleles are expected to be associated with repertoires that overlap multiple supertypes. Interestingly, the current analysis did not identify any additional supertype specificities. CONCLUSION: As a result of this updated analysis, HLA supertype associations have been defined for over 750 different HLA-A and -B alleles. This information is expected to facilitate epitope identification and vaccine design studies, as well as investigations into disease association and correlates of immunity. In addition, the approach utilized has been made more transparent, allowing others to utilize the classification approach going forward.",2008 Jan 22,"['Sidney, John', 'Peters, Bjoern', 'Frahm, Nicole', 'Brander, Christian', 'Sette, Alessandro']",BMC Immunol,,,True
20d1c063410f32eb59b3f3063d506c4888c80bec,PMC,Role of receptor polymorphism and glycosylation in syncytium induction and host range variation of ecotropic mouse gammaretroviruses,http://dx.doi.org/10.1186/1742-4690-5-2,PMC2248597,18186934,CC BY,"BACKGROUND: We previously identified unusual variants of Moloney and Friend ecotropic mouse gammaretroviruses that have altered host range and are cytopathic in cells of the wild mouse species Mus dunni. Cytopathicity was attributed to different amino acid substitutions at the same critical env residue involved in receptor interaction: S82F in the Moloney variant Spl574, and S84A in the Friend mouse leukemia virus F-S MLV. Because M. dunni cells carry a variant CAT-1 cell surface virus receptor (dCAT-1), we examined the role of this receptor variant in cytopathicity and host range. RESULTS: We expressed dCAT-1 or mCAT-1 of NIH 3T3 origin in cells that are not normally infectible with ecotropic MLVs and evaluated the transfectants for susceptibility to virus infection and to virus-induced syncytium formation. The dCAT-1 transfectants, but not the mCAT-1 transfectants, were susceptible to virus-induced cytopathicity, and this cytopathic response was accompanied by the accumulation of unintegrated viral DNA. The dCAT-1 transfectants, however, did not also reproduce the relative resistance of M. dunni cells to Moloney MLV, and the mCAT-1 transfectants did not show the relative resistance of NIH 3T3 cells to Spl574. Western analysis, use of glycosylation inhibitors and mutagenesis to remove receptor glycosylation sites identified a possible role for cell-specific glycosylation in the modulation of virus entry. CONCLUSION: Virus entry and virus-induced syncytium formation using the CAT-1 receptor are mediated by a small number of critical amino acid residues in receptor and virus Env. Virus entry is modulated by glycosylation of cellular proteins, and this effect is cell and virus-specific.",2008 Jan 10,"['Yan, Yuhe', 'Jung, Yong T', 'Wu, Tiyun', 'Kozak, Christine A']",Retrovirology,,,True
63f04bb7051a4d43795615877a0a351ca5d79740,PMC,Establishing a nationwide emergency department-based syndromic surveillance system for better public health responses in Taiwan,http://dx.doi.org/10.1186/1471-2458-8-18,PMC2249581,18201388,CC BY,"BACKGROUND: With international concern over emerging infectious diseases (EID) and bioterrorist attacks, public health is being required to have early outbreak detection systems. A disease surveillance team was organized to establish a hospital emergency department-based syndromic surveillance system (ED-SSS) capable of automatically transmitting patient data electronically from the hospitals responsible for emergency care throughout the country to the Centers for Disease Control in Taiwan (Taiwan-CDC) starting March, 2004. This report describes the challenges and steps involved in developing ED-SSS and the timely information it provides to improve in public health decision-making. METHODS: Between June 2003 and March 2004, after comparing various surveillance systems used around the world and consulting with ED physicians, pediatricians and internal medicine physicians involved in infectious disease control, the Syndromic Surveillance Research Team in Taiwan worked with the Real-time Outbreak and Disease Surveillance (RODS) Laboratory at the University of Pittsburgh to create Taiwan's ED-SSS. The system was evaluated by analyzing daily electronic ED data received in real-time from the 189 hospitals participating in this system between April 1, 2004 and March 31, 2005. RESULTS: Taiwan's ED-SSS identified winter and summer spikes in two syndrome groups: influenza-like illnesses and respiratory syndrome illnesses, while total numbers of ED visits were significantly higher on weekends, national holidays and the days of Chinese lunar new year than weekdays (p < 0.001). It also identified increases in the upper, lower, and total gastrointestinal (GI) syndrome groups starting in November 2004 and two clear spikes in enterovirus-like infections coinciding with the two school semesters. Using ED-SSS for surveillance of influenza-like illnesses and enteroviruses-related infections has improved Taiwan's pandemic flu preparedness and disease control capabilities. CONCLUSION: Taiwan's ED-SSS represents the first nationwide real-time syndromic surveillance system ever established in Asia. The experiences reported herein can encourage other countries to develop their own surveillance systems. The system can be adapted to other cultural and language environments for better global surveillance of infectious diseases and international collaboration.",2008 Jan 18,"['Wu, Tsung-Shu Joseph', 'Shih, Fuh-Yuan Frank', 'Yen, Muh-Yong', 'Wu, Jiunn-Shyan Julian', 'Lu, Shiou-Wen', 'Chang, Kevin Chi-Ming', 'Hsiung, Chao', 'Chou, Jr-How', 'Chu, Yu-Tseng', 'Chang, Hang', 'Chiu, Chan-Hsien', 'Tsui, Fu-Chiang Richard', 'Wagner, Michael M', 'Su, Ih-Jen', 'King, Chwan-Chuen']",BMC Public Health,,,True
f89c1c613071fcb7fdb5d956e91a807b83456ea3,PMC,Effects of intranasal TNFα on granulocyte recruitment and activity in healthy subjects and patients with allergic rhinitis,http://dx.doi.org/10.1186/1465-9921-9-15,PMC2253533,18234086,CC BY,"BACKGROUND: TNFα may contribute to the pathophysiology of airway inflammation. For example, we have recently shown that nasal administration of TNFα produces late phase co-appearance of granulocyte and plasma exudation markers on the mucosal surface. The objective of the present study was to examine indices of granulocyte presence and activity in response to intranasal TNFα challenge. METHODS: Healthy subjects and patients with allergic rhinitis (examined out of season) were subjected to nasal challenge with TNFα (10 μg) in a sham-controlled and crossover design. Nasal lavages were carried out prior to and 24 hours post challenge. Nasal biopsies were obtained post challenge. Nasal lavage fluid levels of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were analyzed as indices of neutrophil and eosinophil activity. Moreover, IL-8 and α(2)-macroglobulin were analyzed as markers of pro-inflammatory cytokine production and plasma exudation. Nasal biopsy numbers of neutrophils and eosinophils were monitored. RESULTS: Nasal lavage fluid levels of MPO recorded 24 hours post TNFα challenge were increased in healthy subjects (p = 0.0081) and in patients with allergic rhinitis (p = 0.0081) (c.f. sham challenge). Similarly, α(2)-macroglobulin was increased in healthy subjects (p = 0.014) and in patients with allergic rhinitis (p = 0.0034). Lavage fluid levels of ECP and IL-8 were not affected by TNFα challenge. TNFα increased the numbers of subepithelial neutrophils (p = 0.0021), but not the numbers of eosinophils. CONCLUSION: TNFα produces a nasal inflammatory response in humans that is characterised by late phase (i.e., 24 hours post challenge) neutrophil activity and plasma exudation.",2008 Jan 30,"['Widegren, Henrik', 'Erjefält, Jonas', 'Korsgren, Magnus', 'Andersson, Morgan', 'Greiff, Lennart']",Respir Res,,,True
06795e24716acde6e56c25d7845c92a97fa0268c,PMC,Viral genome sequencing by random priming methods,http://dx.doi.org/10.1186/1471-2164-9-5,PMC2254600,18179705,CC BY,"BACKGROUND: Most emerging health threats are of zoonotic origin. For the overwhelming majority, their causative agents are RNA viruses which include but are not limited to HIV, Influenza, SARS, Ebola, Dengue, and Hantavirus. Of increasing importance therefore is a better understanding of global viral diversity to enable better surveillance and prediction of pandemic threats; this will require rapid and flexible methods for complete viral genome sequencing. RESULTS: We have adapted the SISPA methodology [1-3] to genome sequencing of RNA and DNA viruses. We have demonstrated the utility of the method on various types and sources of viruses, obtaining near complete genome sequence of viruses ranging in size from 3,000–15,000 kb with a median depth of coverage of 14.33. We used this technique to generate full viral genome sequence in the presence of host contaminants, using viral preparations from cell culture supernatant, allantoic fluid and fecal matter. CONCLUSION: The method described is of great utility in generating whole genome assemblies for viruses with little or no available sequence information, viruses from greatly divergent families, previously uncharacterized viruses, or to more fully describe mixed viral infections.",2008 Jan 7,"['Djikeng, Appolinaire', 'Halpin, Rebecca', 'Kuzmickas, Ryan', 'DePasse, Jay', 'Feldblyum, Jeremy', 'Sengamalay, Naomi', 'Afonso, Claudio', 'Zhang, Xinsheng', 'Anderson, Norman G', 'Ghedin, Elodie', 'Spiro, David J']",BMC Genomics,,,True
308e91d0c4575362a0d169b9ed31c60f79a86437,PMC,Tear lipocalin is the major endonuclease in tears,,PMC2254967,18334931,CC BY,"PURPOSE: Human endonucleases are integral to apoptosis in which unwanted or potentially harmful cells are eliminated. The rapid turnover of ocular surface epithelium and microbial colonization of the eyelids are continual sources of DNA in tears. Here, we determine the principal sources of endonuclease activity in tears. METHODS: Endonucleases in human tears were identified after Sephadex G100 gel filtration. DNA hydrolyzing activity was measured by the conversion pUC19 plasmid DNA to its circular form in agarose gels. Fractions with endonuclease activity were further isolated using a combination ConA-Sepharose DNA, oligo (dT) cellulose, and anion exchange chromatographies. The molecular weights of the DNA hydrolyzing proteins were estimated in zymograms and by calibration of size exclusion chromatography. DNase activities were characterized for activity at a variety of pH and ion concentrations as well as in the presence of inhibitors including NiCl(2), ZnCl(2), G-actin, and aurintricarboxylic acid (ATA). To determine the mode of hydrolysis, the cleaved ends of the DNA digested by tear DNases were analyzed by 3′ and 5′ end labeling using either terminal deoxynucleotidyl transferase or polynucleotide kinase with or without pretreatment with alkaline phosphatase. RESULTS: Tear lipocalin (TL) accounts for over 75% of the DNA catalytic activity in tears while a second endonuclease, ~34 kDa, is responsible for less than 24% of the activity. Both are Mg(2+) dependent enzyme endonucleases that are enhanced by Ca(2+), active at physiologic pH, inhibited by aurintricarboxylic acid, and catalyze hydrolysis of DNA to produce 3′-OH/5′P ends. However, the two enzymes can be distinguished by the inhibitory effect of NiCl(2) and the sizes of the cleaved DNA fragments. CONCLUSIONS: Two magnesium dependent extracellular endonucleases were identified in tears that are different from other major human extracellular nucleases. TL is the principal endonuclease in human tear fluid. Tear endonucleases have unique characteristics that differ from other known human endonucleases.",2008 Jan 29,"['Yusifov, Taleh N.', 'Abduragimov, Adil R.', 'Narsinh, Kiran', 'Gasymov, Oktay K.', 'Glasgow, Ben J.']",Mol Vis,,,True
eb4b8f43f68db5e493984b7e4e56d9f804d7e885,PMC,Can the concept of Health Promoting Schools help to improve students' health knowledge and practices to combat the challenge of communicable diseases: Case study in Hong Kong?,http://dx.doi.org/10.1186/1471-2458-8-42,PMC2258284,18234083,CC BY,"BACKGROUND: The growing epidemics of emerging infectious diseases has raised the importance of a setting approach and include the Health Promoting School (HPS) framework to promote better health and hygiene. Built on the concept of 'the' HPS framework, the Hong Kong Healthy Schools Award scheme includes ""Personal Health Skills"" as one of its key aspects to improve student hygiene knowledge and practices. This study examines the differences in student perceptions, knowledge and health behaviours between those schools that have adopted the HPS framework and those that have not adopted. METHODS: A cross-sectional study using multi-stage random sampling was conducted among schools with awards (HSA) and those schools not involved in the award scheme nor adopting the concept of HPS (non-HPS). For HSA group, 5 primary schools and 7 secondary schools entered the study with 510 students and 789 students sampled respectively. For the 'Non-HPS' group, 8 primary schools and 7 secondary schools entered the study with 676 students and 725 students sampled respectively. A self-administered questionnaire was used as the measuring instrument. RESULTS: Students in the HSA category were found to be better with statistical significance in personal hygiene practice, knowledge on health and hygiene, as well as access to health information. HSA schools were reported to have better school health policy, higher degrees of community participation, and better hygienic environment. CONCLUSION: Students in schools that had adopted the HPS framework had a more positive health behaviour profile than those in non-HPS schools. Although a causal relationship is yet to be established, the HPS appears to be a viable approach for addressing communicable diseases.",2008 Jan 30,"['Lee, Albert', 'Wong, Martin CS', 'Keung, Vera MW', 'Yuen, Hilda SK', 'Cheng, Frances', 'Mok, Jennifer SY']",BMC Public Health,,,True
d77dcb77a4a620fd1de81f309bff0e04e2578272,PMC,Hotspot Hunter: a computational system for large-scale screening and selection of candidate immunological hotspots in pathogen proteomes,http://dx.doi.org/10.1186/1471-2105-9-S1-S19,PMC2259420,18315850,CC BY,"BACKGROUND: T-cell epitopes that promiscuously bind to multiple alleles of a human leukocyte antigen (HLA) supertype are prime targets for development of vaccines and immunotherapies because they are relevant to a large proportion of the human population. The presence of clusters of promiscuous T-cell epitopes, immunological hotspots, has been observed in several antigens. These clusters may be exploited to facilitate the development of epitope-based vaccines by selecting a small number of hotspots that can elicit all of the required T-cell activation functions. Given the large size of pathogen proteomes, including of variant strains, computational tools are necessary for automated screening and selection of immunological hotspots. RESULTS: Hotspot Hunter is a web-based computational system for large-scale screening and selection of candidate immunological hotspots in pathogen proteomes through analysis of antigenic diversity. It allows screening and selection of hotspots specific to four common HLA supertypes, namely HLA class I A2, A3, B7 and class II DR. The system uses Artificial Neural Network and Support Vector Machine methods as predictive engines. Soft computing principles were employed to integrate the prediction results produced by both methods for robust prediction performance. Experimental validation of the predictions showed that Hotspot Hunter can successfully identify majority of the real hotspots. Users can predict hotspots from a single protein sequence, or from a set of aligned protein sequences representing pathogen proteome. The latter feature provides a global view of the localizations of the hotspots in the proteome set, enabling analysis of antigenic diversity and shift of hotspots across protein variants. The system also allows the integration of prediction results of the four supertypes for identification of hotspots common across multiple supertypes. The target selection feature of the system shortlists candidate peptide hotspots for the formulation of an epitope-based vaccine that could be effective against multiple variants of the pathogen and applicable to a large proportion of the human population. CONCLUSION: Hotspot Hunter is publicly accessible at . It is a new generation computational tool aiding in epitope-based vaccine design.",2008 Feb 13,"['Zhang, Guang Lan', 'Khan, Asif M', 'Srinivasan, Kellathur N', 'Heiny, AT', 'Lee, KX', 'Kwoh, Chee Keong', 'August, J Thomas', 'Brusic, Vladimir']",BMC Bioinformatics,,,True
111968f7fb102882c193488965e41d5d0f0103dc,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,True
40a9af5b24845df11d024ef657f7c91ffd6871f4,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
02f6c1a9ceadd3a52df836f08c84f0c37d01fc92,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
f27cd7dcbc541ade60e624d3b8a01271b8bc0994,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
3780a3ec4d25889c7a447b1c664d4c35e5031b0d,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
7a3ae584544d0a1c7bf4fd406dd23216e30e45e8,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
94958f7e5269bf74f113e80e2ec1b26a95a44d50,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
279ac6b430bb584496e226d0ae4bb19aace9bcff,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
70b0b8c7e82529cbdf874ec2932446edff21aa74,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
153dc20c0306ef3ec12ea5d4316b63d8ddc78ca1,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
cb00f85d57af6c0f4b1e24f81e121641f53715a5,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
0dd0ea8ef4cd2637dff19c517d7b0f21b323c0c8,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
e11481664a0ba85ec7117fa32f147c10681065ef,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
db5b99eac0c11848467c40af5744442e0b869870,PMC,Universal primers that amplify RNA from all three flavivirus subgroups,http://dx.doi.org/10.1186/1743-422X-5-16,PMC2263041,18218114,CC BY,"BACKGROUND: Species within the Flavivirus genus pose public health problems around the world. Increasing cases of Dengue and Japanese encephalitis virus in Asia, frequent outbreaks of Yellow fever virus in Africa and South America, and the ongoing spread of West Nile virus throughout the Americas, show the geographical burden of flavivirus diseases. Flavivirus infections are often indistinct from and confused with other febrile illnesses. Here we review the specificity of published primers, and describe a new universal primer pair that can detect a wide range of flaviviruses, including viruses from each of the recognised subgroups. RESULTS: Bioinformatic analysis of 257 published full-length Flavivirus genomes revealed conserved regions not previously targeted by primers. Two degenerate primers, Flav100F and Flav200R were designed from these regions and used to generate an 800 base pair cDNA product. The region amplified encoded part of the methyltransferase and most of the RNA-dependent-RNA-polymerase (NS5) coding sequence. One-step RT-PCR testing was successful using standard conditions with RNA from over 60 different flavivirus strains representing about 50 species. The cDNA from each virus isolate was sequenced then used in phylogenetic analyses and database searches to confirm the identity of the template RNA. CONCLUSION: Comprehensive testing has revealed the broad specificity of these primers. We briefly discuss the advantages and uses of these universal primers.",2008 Jan 24,"['Maher-Sturgess, Sheryl L', 'Forrester, Naomi L', 'Wayper, Paul J', 'Gould, Ernest A', 'Hall, Roy A', 'Barnard, Ross T', 'Gibbs, Mark J']",Virol J,,,True
aae7699e079d2964df8078931cd0f94d4b1423d9,PMC,Amino Acid Similarity Accounts for T Cell Cross-Reactivity and for “Holes” in the T Cell Repertoire,http://dx.doi.org/10.1371/journal.pone.0001831,PMC2263130,18350167,CC0,"BACKGROUND: Cytotoxic T cell (CTL) cross-reactivity is believed to play a pivotal role in generating immune responses but the extent and mechanisms of CTL cross-reactivity remain largely unknown. Several studies suggest that CTL clones can recognize highly diverse peptides, some sharing no obvious sequence identity. The emerging realization in the field is that T cell receptors (TcR) recognize multiple distinct ligands. PRINCIPAL FINDINGS: First, we analyzed peptide scans of the HIV epitope SLFNTVATL (SFL9) and found that TCR specificity is position dependent and that biochemically similar amino acid substitutions do not drastically affect recognition. Inspired by this, we developed a general model of TCR peptide recognition using amino acid similarity matrices and found that such a model was able to predict the cross-reactivity of a diverse set of CTL epitopes. With this model, we were able to demonstrate that seemingly distinct T cell epitopes, i.e., ones with low sequence identity, are in fact more biochemically similar than expected. Additionally, an analysis of HIV immunogenicity data with our model showed that CTLs have the tendency to respond mostly to peptides that do not resemble self-antigens. CONCLUSIONS: T cell cross-reactivity can thus, to an extent greater than earlier appreciated, be explained by amino acid similarity. The results presented in this paper will help resolving some of the long-lasting discussions in the field of T cell cross-reactivity.",2008 Mar 19,"['Frankild, Sune', 'de Boer, Rob J.', 'Lund, Ole', 'Nielsen, Morten', 'Kesmir, Can']",PLoS One,,,True
15372a2da42ddcb56ac4edc88090a6a425c5fad0,PMC,The cost of community-managed viral respiratory illnesses in a cohort of healthy preschool-aged children,http://dx.doi.org/10.1186/1465-9921-9-11,PMC2266731,18215329,CC BY,"BACKGROUND: Acute respiratory illnesses (ARIs) during childhood are often caused by respiratory viruses, result in significant morbidity, and have associated costs for families and society. Despite their ubiquity, there is a lack of interdisciplinary epidemiologic and economic research that has collected primary impact data, particularly associated with indirect costs, from families during ARIs in children. METHODS: We conducted a 12-month cohort study in 234 preschool children with impact diary recording and PCR testing of nose-throat swabs for viruses during an ARI. We used applied values to estimate a virus-specific mean cost of ARIs. RESULTS: Impact diaries were available for 72% (523/725) of community-managed illnesses between January 2003 and January 2004. The mean cost of ARIs was AU$309 (95% confidence interval $263 to $354). Influenza illnesses had a mean cost of $904, compared with RSV, $304, the next most expensive single-virus illness, although confidence intervals overlapped. Mean carer time away from usual activity per day was two hours for influenza ARIs and between 30 and 45 minutes for all other ARI categories. CONCLUSION: From a societal perspective, community-managed ARIs are a significant cost burden on families and society. The point estimate of the mean cost of community-managed influenza illnesses in healthy preschool aged children is three times greater than those illnesses caused by RSV and other respiratory viruses. Indirect costs, particularly carer time away from usual activity, are the key cost drivers for ARIs in children. The use of parent-collected specimens may enhance ARI surveillance and reduce any potential Hawthorne effect caused by compliance with study procedures. These findings reinforce the need for further integrated epidemiologic and economic research of ARIs in children to allow for comprehensive cost-effectiveness assessments of preventive and therapeutic options.",2008 Jan 24,"['Lambert, Stephen B', 'Allen, Kelly M', 'Carter, Robert C', 'Nolan, Terence M']",Respir Res,,,True
ab54f13666ed771c15684d73ff6bcc7c92b8ae05,PMC,Validity of the Common Cold Questionnaire (CCQ) in Asthma Exacerbations,http://dx.doi.org/10.1371/journal.pone.0001802,PMC2266793,18350141,CC BY,"BACKGROUND: The common cold questionnaire (CCQ) is used to discriminate those with and without a viral infection. Its usefulness in people with acute asthma is unknown. Our aim was to assess the ability of the CCQ to detect viral infection and to monitor recovery during a viral induced asthma exacerbation and confirmed by virological testing. METHODOLOGY/PRINCIPAL FINDINGS: We studied subjects (≥7 yrs) admitted to hospital with acute asthma and diagnosed as positive (n = 63), or negative to viral infection (n = 27) according to molecular and virological testing from respiratory samples. CCQ, asthma history and asthma control questionnaires were completed and repeated 4–6 weeks later. Sensitivity, specificity, and response to change of the CCQ were assessed by receiver operator curve (ROC) analysis and effect size calculation respectively. The CCQ did not discriminate between viral and non-viral infection for subjects with asthma (sensitivity = 76.2%; specificity = 29.6%). ROC analysis could not differentiate between positive or negative virus in subjects with asthma. The CCQ had a large response to change following recovery (effect size = 1.01). 39% of subjects recovering from viral exacerbation remained positive to virological testing at follow-up despite improvement in clinical symptoms. The CCQ reflected clinical improvement in these subjects, thus providing additional information to complement virological testing. CONCLUSIONS/SIGNIFICANCE: The CCQ is a useful instrument for monitoring response to viral infection in people with asthma. Reliable differentiation between viral and non-viral asthma exacerbations was not achieved with the CCQ and requires specific virological testing. When combined with virological testing, the CCQ should be a useful outcome measure for evaluating therapies in viral-induced asthma.",2008 Mar 19,"['Powell, Heather', 'Smart, Joanne', 'Wood, Lisa G.', 'Grissell, Terry', 'Shafren, Darren R.', 'Hensley, Michael J.', 'Gibson, Peter G.']",PLoS One,,,True
e6f54fcf3460165fb558903e975a526bc98e4eba,PMC,A Virus-Encoded Cell–Cell Fusion Machine Dependent on Surrogate Adhesins,http://dx.doi.org/10.1371/journal.ppat.1000016,PMC2267009,18369467,CC BY,"The reovirus fusion-associated small transmembrane (FAST) proteins function as virus-encoded cellular fusogens, mediating efficient cell–cell rather than virus–cell membrane fusion. With ectodomains of only ∼20–40 residues, it is unclear how such diminutive viral fusion proteins mediate the initial stages (i.e. membrane contact and close membrane apposition) of the fusion reaction that precede actual membrane merger. We now show that the FAST proteins lack specific receptor-binding activity, and in their natural biological context of promoting cell–cell fusion, rely on cadherins to promote close membrane apposition. The FAST proteins, however, are not specifically reliant on cadherin engagement to mediate membrane apposition as indicated by their ability to efficiently utilize other adhesins in the fusion reaction. Results further indicate that surrogate adhesion proteins that bridge membranes as close as 13 nm apart enhance FAST protein-induced cell–cell fusion, but active actin remodelling is required for maximal fusion activity. The FAST proteins are the first example of membrane fusion proteins that have specifically evolved to function as opportunistic fusogens, designed to exploit and convert naturally occurring adhesion sites into fusion sites. The capacity of surrogate, non-cognate adhesins and active actin remodelling to enhance the cell–cell fusion activity of the FAST proteins are features perfectly suited to the structural and functional evolution of these fusogens as the minimal fusion component of a virus-encoded cellular fusion machine. These results also provide a basis for reconciling the rudimentary structure of the FAST proteins with their capacity to fuse cellular membranes.",2008 Mar 7,"['Salsman, Jayme', 'Top, Deniz', 'Barry, Christopher', 'Duncan, Roy']",PLoS Pathog,,,True
3f7c34653f6fcd0675f13b47461b74cd0f0a51fd,PMC,Membrane interaction and structure of the transmembrane domain of influenza hemagglutinin and its fusion peptide complex,http://dx.doi.org/10.1186/1741-7007-6-2,PMC2267159,18197965,CC BY,"BACKGROUND: To study the organization and interaction with the fusion domain (or fusion peptide, FP) of the transmembrane domain (TMD) of influenza virus envelope glycoprotein for its role in membrane fusion which is also essential in the cellular trafficking of biomolecules and sperm-egg fusion. RESULTS: The fluorescence and gel electrophoresis experiments revealed a tight self-assembly of TMD in the model membrane. A weak but non-random interaction between TMD and FP in the membrane was found. In the complex, the central TMD oligomer was packed by FP in an antiparallel fashion. FP insertion into the membrane was altered by binding to TMD. An infrared study exhibited an enhanced membrane perturbation by the complex formation. A model was built to illustrate the role of TMD in the late stages of influenza virus-mediated membrane fusion reaction. CONCLUSION: The TMD oligomer anchors the fusion protein in the membrane with minimal destabilization to the membrane. Upon associating with FP, the complex exerts a synergistic effect on the membrane perturbation. This effect is likely to contribute to the complete membrane fusion during the late phase of fusion protein-induced fusion cascade. The results presented in the work characterize the nature of the interaction of TMD with the membrane and TMD in a complex with FP in the steps leading to pore initiation and dilation during virus-induced fusion. Our data and proposed fusion model highlight the key role of TMD-FP interaction and have implications on the fusion reaction mediated by other type I viral fusion proteins. Understanding the molecular mechanism of membrane fusion may assist in the design of anti-viral drugs.",2008 Jan 15,"['Chang, Ding-Kwo', 'Cheng, Shu-Fang', 'Kantchev, Eric Aseen B', 'Lin, Chi-Hui', 'Liu, Yu-Tsan']",BMC Biol,,,True
00acd3fd31ed0cde8df286697caefc5298e54df1,PMC,"Distinguishing Molecular Features and Clinical Characteristics of a Putative New Rhinovirus Species, Human Rhinovirus C (HRV C)",http://dx.doi.org/10.1371/journal.pone.0001847,PMC2268738,18382652,CC BY,"BACKGROUND: Human rhinoviruses (HRVs) are the most frequently detected pathogens in acute respiratory tract infections (ARTIs) and yet little is known about the prevalence, recurrence, structure and clinical impact of individual members. During 2007, the complete coding sequences of six previously unknown and highly divergent HRV strains were reported. To catalogue the molecular and clinical features distinguishing the divergent HRV strains, we undertook, for the first time, in silico analyses of all available polyprotein sequences and performed retrospective reviews of the medical records of cases in which variants of the prototype strain, HRV-QPM, had been detected. METHODOLOGY/PRINCIPLE FINDINGS: Genomic analyses revealed that the six divergent strains, residing within a clade we previously called HRV A2, had the shortest polyprotein of all picornaviruses investigated. Structure-based amino acid alignments identified conserved motifs shared among members of the genus Rhinovirus as well as substantive deletions and insertions unique to the divergent strains. Deletions mostly affected regions encoding proteins traditionally involved in antigenicity and serving as HRV and HEV receptor footprints. Because the HRV A2 strains cannot yet be cultured, we created homology models of predicted HRV-QPM structural proteins. In silico comparisons confirmed that HRV-QPM was most closely related to the major group HRVs. HRV-QPM was most frequently detected in infants with expiratory wheezing or persistent cough who had been admitted to hospital and required supplemental oxygen. It was the only virus detected in 65% of positive individuals. These observations contributed to an objective clinical impact ranging from mild to severe. CONCLUSIONS: The divergent strains did not meet classification requirements for any existing species of the genus Rhinovirus or Enterovirus. HRV A2 strains should be partitioned into at least one new species, putatively called Human rhinovirus C, populated by members detected with high frequency, from individuals with respiratory symptoms requiring hospital admission.",2008 Apr 2,"['McErlean, Peter', 'Shackelton, Laura A.', 'Andrews, Emily', 'Webster, Dale R.', 'Lambert, Stephen B.', 'Nissen, Michael D.', 'Sloots, Theo P.', 'Mackay, Ian M.']",PLoS One,,,True
808dfc4c59f3e2e9150aa5542ea227718741388b,PMC,Towards a Coronavirus-Based HIV Multigene Vaccine,http://dx.doi.org/10.1080/17402520600579168,PMC2270750,17162377,CC BY,"Human immunodeficiency virus (HIV) infection represents one of the major health threats in the developing world. The costly treatment of infected individuals with multiple highly efficient anti-HIV drugs is only affordable in industrialized countries. Thus, an efficient vaccination strategy is required to prevent the further spread of the infection. The molecular biology of coronaviruses and particular features of the human coronavirus 229E (HCoV 229E) indicate that HCoV 229E-based vaccine vectors can become a new class of highly efficient vaccines. First, the receptor of HCoV 229E, human aminopeptidase N (hAPN or CD13) is expressed mainly on human dendritic cells (DCs) and macrophages indicating that targeting of HCoV 229E-based vectors to professional antigen presenting cells can be achieved by receptor-mediated transduction. Second, HCoV 229E structural genes can be replaced by multiple transcriptional units encoding various antigens. These virus-like particles (VLPs) containing HCoV 229E-based vector RNA have the ability to transduce human DCs and to mediate heterologous gene expression in these cells. Finally, coronavirus infections are associated with mainly respiratory and enteric diseases, and natural transmission of coronaviruses occurs via mucosal surfaces. In humans, HCoV 229E causes common cold by infecting the upper respiratory tract. HCoV 229E infections are mainly encountered in children and re-infection occurs frequently in adults. It is thus most likely that pre-existing immunity against HCoV 229E will not significantly impact on the vaccination efficiency if HCoV 229E-based vectors are used in humans.",2006 Jun-Dec,"['Eriksson, Klara K.', 'Makia, Divine', 'Maier, Reinhard', 'Ludewig, Burkhard', 'Thiel, Volker']",Clin Dev Immunol,,,True
5e2457559eab2f9b131de9084d5dfc66bd875aee,PMC,Identification of a contemporary human parechovirus type 1 by VIDISCA and characterisation of its full genome,http://dx.doi.org/10.1186/1743-422X-5-26,PMC2270820,18269761,CC BY,"BACKGROUND: Enteritis is caused by a spectrum of viruses that is most likely not fully characterised. When testing stool samples by cell culture, virus isolates are sometimes obtained which cannot be typed by current methods. In this study we used VIDISCA, a virus identification method which has not yet been widely applied, on such an untyped virus isolate. RESULTS: We found a human parechovirus (HPeV) type 1 (strain designation: BNI-788st). Because genomes of contemporary HPeV1 were not available, we determined its complete genome sequence. We found that the novel strain was likely the result of recombination between structural protein genes of an ancestor of contemporary HPeV1 strains and nonstructural protein genes from an unknown ancestor, most closely related to HPeV3. In contrast to the non-structural protein genes of other HPeV prototype strains, the non-structural protein genes of BNI-788st and HPeV3 prototype strains did not co-segregate in bootscan analysis with that of other prototype strains. CONCLUSION: HPeV3 nonstructural protein genes may form a distinct element in a pool of circulating HPeV non-structural protein genes. More research into the complex HPeV evolution is required to connect virus ecology with disease patterns in humans.",2008 Feb 12,"['de Souza Luna, Luciano Kleber', 'Baumgarte, Sigrid', 'Grywna, Klaus', 'Panning, Marcus', 'Drexler, Jan Felix', 'Drosten, Christian']",Virol J,,,True
eb4e468f68974db552de7a9f4e41d95607b0c461,PMC,"Genomic organization, sequence divergence, and recombination of feline immunodeficiency virus from lions in the wild",http://dx.doi.org/10.1186/1471-2164-9-66,PMC2270836,18251995,CC BY,"BACKGROUND: Feline immunodeficiency virus (FIV) naturally infects multiple species of cat and is related to human immunodeficiency virus in humans. FIV infection causes AIDS-like disease and mortality in the domestic cat (Felis catus) and serves as a natural model for HIV infection in humans. In African lions (Panthera leo) and other exotic felid species, disease etiology introduced by FIV infection are less clear, but recent studies indicate that FIV causes moderate to severe CD4 depletion. RESULTS: In this study, comparative genomic methods are used to evaluate the full proviral genome of two geographically distinct FIV subtypes isolated from free-ranging lions. Genome organization of FIV(Ple )subtype B (9891 bp) from lions in the Serengeti National Park in Tanzania and FIV(Ple )subtype E (9899 bp) isolated from lions in the Okavango Delta in Botswana, both resemble FIV genome sequence from puma, Pallas cat and domestic cat across 5' LTR, gag, pol, vif, orfA, env, rev and 3'LTR regions. Comparative analyses of available full-length FIV consisting of subtypes A, B and C from FIV(Fca), Pallas cat FIV(Oma )and two puma FIV(Pco )subtypes A and B recapitulate the species-specific monophyly of FIV marked by high levels of genetic diversity both within and between species. Across all FIV(Ple )gene regions except env, lion subtypes B and E are monophyletic, and marginally more similar to Pallas cat FIV(Oma )than to other FIV. Sequence analyses indicate the SU and TM regions of env vary substantially between subtypes, with FIV(Ple )subtype E more related to domestic cat FIV(Fca )than to FIV(Ple) subtype B and FIV(Oma )likely reflecting recombination between strains in the wild. CONCLUSION: This study demonstrates the necessity of whole-genome analysis to complement population/gene-based studies, which are of limited utility in uncovering complex events such as recombination that may lead to functional differences in virulence and pathogenicity. These full-length lion lentiviruses are integral to the advancement of comparative genomics of human pathogens, as well as emerging disease in wild populations of endangered species.",2008 Feb 5,"['Pecon-Slattery, Jill', 'McCracken, Carrie L', 'Troyer, Jennifer L', 'VandeWoude, Sue', 'Roelke, Melody', 'Sondgeroth, Kerry', 'Winterbach, Christiaan', 'Winterbach, Hanlie', ""O'Brien, Stephen J""]",BMC Genomics,,,True
aa34a2ba35c3daf0b882dfa8b96e65aa251b5ea8,PMC,Epigrass: a tool to study disease spread in complex networks,http://dx.doi.org/10.1186/1751-0473-3-3,PMC2275240,18302744,CC BY,"BACKGROUND: The construction of complex spatial simulation models such as those used in network epidemiology, is a daunting task due to the large amount of data involved in their parameterization. Such data, which frequently resides on large geo-referenced databases, has to be processed and assigned to the various components of the model. All this just to construct the model, then it still has to be simulated and analyzed under different epidemiological scenarios. This workflow can only be achieved efficiently by computational tools that can automate most, if not all, these time-consuming tasks. In this paper, we present a simulation software, Epigrass, aimed to help designing and simulating network-epidemic models with any kind of node behavior. RESULTS: A Network epidemiological model representing the spread of a directly transmitted disease through a bus-transportation network connecting mid-size cities in Brazil. Results show that the topological context of the starting point of the epidemic is of great importance from both control and preventive perspectives. CONCLUSION: Epigrass is shown to facilitate greatly the construction, simulation and analysis of complex network models. The output of model results in standard GIS file formats facilitate the post-processing and analysis of results by means of sophisticated GIS software.",2008 Feb 26,"['Coelho, Flávio C', 'Cruz, Oswaldo G', 'Codeço, Cláudia T']",Source Code Biol Med,,,True
66f425e847bc112e32f81cac4c2c57b1b6d0f284,PMC,Autoimmune Cholangitis in the SJL/J Mouse is Antigen Non-specific,http://dx.doi.org/10.1080/1044667021000096455,PMC2276095,12739787,CC BY,"Primary biliary cirrhosis (PBC) is an autoimmune disease characterized by intrahepatic bile duct destruction and the production of anti-mitochondrial antibodies (AMA). The absence of an animal model has been a striking impedance in defining the molecular basis of disease. Previous work has suggested that SJL/J mice immunize with the pyruvate dehydrogenase complex (PDC-E2), the major mitochondrial autoantigen of PBC, leads to the development of lymphoid cell infiltration in portal tracts and a model system coined autoimmune cholangitis. We hypothesized that this pathology would be augmented if immunization occurred in the presence of IFN-γ injections. Accordingly, SJL/J mice were immunized with PDC-E2 and, for purpose of control, α-casein. Subgroups of mice were also treated with exogenous IFN-γ. As expected, mice immunized with PDC-E2, with or without IFN-γ, developed high titer AMAs. In contrast, mice immunized with α-casein, develop antinuclear antibodies. More importantly, the livers from mice immunized with PDC-E2 and/or those immunized with α-casein all displayed lymphoid cell infiltration to the portal tracts, irrespective of bile duct size. Indeed, there was no significant difference between the experimental and the control groups by histologic analysis. Thus, autoimmune cholangitis in these mice is antigen non-specific.",2002 Jun,"['Sasaki, Motoko', 'Allina, Jorge', 'Odin, Joseph A.', 'Thung, Swan N.', 'Coppel, Ross', 'Nakanuma, Yasuni', 'Gershwin, M. Eric']",Dev Immunol,,,True
060201d43460ac305a26ac4b0acca66cd41c151a,PMC,The Search for a Practical Approach to Emerging Diseases: The Case of Severe Acute Respiratory Syndrome (SARS),http://dx.doi.org/10.1080/1044667031000137575,PMC2276106,12885151,CC BY,"The plague, which the Board of Health had feared might enter with the German troops into the Milanese, had entered it indeed, as is well known; and it is likewise well known, that it paused not here, but invaded and ravaged a great part of Italy. (A. Manzoni, The Bethrothed, 1826)",2002 Sep,"['Selmi, Carlo', 'Ansari, Aftab A.', 'Invernizzi, Pietro', 'Podda, Mauro', 'Gershwin, M. Eric']",Dev Immunol,,,True
050e73f86cfa4ab3f3fc84b0cb55ac779fb9abc2,PMC,"La Crosse virus infectivity, pathogenesis, and immunogenicity in mice and monkeys",http://dx.doi.org/10.1186/1743-422X-5-25,PMC2276200,18267012,CC BY,"BACKGROUND: La Crosse virus (LACV), family Bunyaviridae, was first identified as a human pathogen in 1960 after its isolation from a 4 year-old girl with fatal encephalitis in La Crosse, Wisconsin. LACV is a major cause of pediatric encephalitis in North America and infects up to 300,000 persons each year of which 70–130 result in severe disease of the central nervous system (CNS). As an initial step in the establishment of useful animal models to support vaccine development, we examined LACV infectivity, pathogenesis, and immunogenicity in both weanling mice and rhesus monkeys. RESULTS: Following intraperitoneal inoculation of mice, LACV replicated in various organs before reaching the CNS where it replicates to high titer causing death from neurological disease. The peripheral site where LACV replicates to highest titer is the nasal turbinates, and, presumably, LACV can enter the CNS via the olfactory neurons from nasal olfactory epithelium. The mouse infectious dose(50 )and lethal dose(50 )was similar for LACV administered either intranasally or intraperitoneally. LACV was highly infectious for rhesus monkeys and infected 100% of the animals at 10 PFU. However, the infection was asymptomatic, and the monkeys developed a strong neutralizing antibody response. CONCLUSION: In mice, LACV likely gains access to the CNS via the blood stream or via olfactory neurons. The ability to efficiently infect mice intranasally raises the possibility that LACV might use this route to infect its natural hosts. Rhesus monkeys are susceptible to LACV infection and develop strong neutralizing antibody responses after inoculation with as little as 10 PFU. Mice and rhesus monkeys are useful animal models for LACV vaccine immunologic testing although the rhesus monkey model is not optimal.",2008 Feb 11,"['Bennett, Richard S', 'Cress, Christina M', 'Ward, Jerrold M', 'Firestone, Cai-Yen', 'Murphy, Brian R', 'Whitehead, Stephen S']",Virol J,,,True
3370214f4f7242b2a6ef23df718ef0f8b863a04c,PMC,Transmission Pathways of Foot-and-Mouth Disease Virus in the United Kingdom in 2007,http://dx.doi.org/10.1371/journal.ppat.1000050,PMC2277462,18421380,CC BY,"Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs. Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contaminated persons, objects, and aerosols). Here, we show that the outbreaks of FMD in the United Kingdom in August 2007 were caused by a derivative of FMDV O(1) BFS 1860, a virus strain handled at two FMD laboratories located on a single site at Pirbright in Surrey. Genetic analysis of complete viral genomes generated in real-time reveals a probable chain of transmission events, predicting undisclosed infected premises, and connecting the second cluster of outbreaks in September to those in August. Complete genome sequence analysis of FMD viruses conducted in real-time have identified the initial and intermediate sources of these outbreaks and demonstrate the value of such techniques in providing information useful to contemporary disease control programmes.",2008 Apr 18,"['Cottam, Eleanor M.', 'Wadsworth, Jemma', 'Shaw, Andrew E.', 'Rowlands, Rebecca J.', 'Goatley, Lynnette', 'Maan, Sushila', 'Maan, Narender S.', 'Mertens, Peter P. C.', 'Ebert, Katja', 'Li, Yanmin', 'Ryan, Eoin D.', 'Juleff, Nicholas', 'Ferris, Nigel P.', 'Wilesmith, John W.', 'Haydon, Daniel T.', 'King, Donald P.', 'Paton, David J.', 'Knowles, Nick J.']",PLoS Pathog,,,True
444faa5fa90cd457f9f318f5151cc6c93017bae5,PMC,Transmission Pathways of Foot-and-Mouth Disease Virus in the United Kingdom in 2007,http://dx.doi.org/10.1371/journal.ppat.1000050,PMC2277462,18421380,CC BY,"Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs. Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contaminated persons, objects, and aerosols). Here, we show that the outbreaks of FMD in the United Kingdom in August 2007 were caused by a derivative of FMDV O(1) BFS 1860, a virus strain handled at two FMD laboratories located on a single site at Pirbright in Surrey. Genetic analysis of complete viral genomes generated in real-time reveals a probable chain of transmission events, predicting undisclosed infected premises, and connecting the second cluster of outbreaks in September to those in August. Complete genome sequence analysis of FMD viruses conducted in real-time have identified the initial and intermediate sources of these outbreaks and demonstrate the value of such techniques in providing information useful to contemporary disease control programmes.",2008 Apr 18,"['Cottam, Eleanor M.', 'Wadsworth, Jemma', 'Shaw, Andrew E.', 'Rowlands, Rebecca J.', 'Goatley, Lynnette', 'Maan, Sushila', 'Maan, Narender S.', 'Mertens, Peter P. C.', 'Ebert, Katja', 'Li, Yanmin', 'Ryan, Eoin D.', 'Juleff, Nicholas', 'Ferris, Nigel P.', 'Wilesmith, John W.', 'Haydon, Daniel T.', 'King, Donald P.', 'Paton, David J.', 'Knowles, Nick J.']",PLoS Pathog,,,False
f14d0b6eecd99d0bc6afefbb3db486a895ce2efc,PMC,Transmission Pathways of Foot-and-Mouth Disease Virus in the United Kingdom in 2007,http://dx.doi.org/10.1371/journal.ppat.1000050,PMC2277462,18421380,CC BY,"Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs. Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contaminated persons, objects, and aerosols). Here, we show that the outbreaks of FMD in the United Kingdom in August 2007 were caused by a derivative of FMDV O(1) BFS 1860, a virus strain handled at two FMD laboratories located on a single site at Pirbright in Surrey. Genetic analysis of complete viral genomes generated in real-time reveals a probable chain of transmission events, predicting undisclosed infected premises, and connecting the second cluster of outbreaks in September to those in August. Complete genome sequence analysis of FMD viruses conducted in real-time have identified the initial and intermediate sources of these outbreaks and demonstrate the value of such techniques in providing information useful to contemporary disease control programmes.",2008 Apr 18,"['Cottam, Eleanor M.', 'Wadsworth, Jemma', 'Shaw, Andrew E.', 'Rowlands, Rebecca J.', 'Goatley, Lynnette', 'Maan, Sushila', 'Maan, Narender S.', 'Mertens, Peter P. C.', 'Ebert, Katja', 'Li, Yanmin', 'Ryan, Eoin D.', 'Juleff, Nicholas', 'Ferris, Nigel P.', 'Wilesmith, John W.', 'Haydon, Daniel T.', 'King, Donald P.', 'Paton, David J.', 'Knowles, Nick J.']",PLoS Pathog,,,False
330c656592e9917ebc7c9c1703ddaa3d9df809bf,PMC,Proteomics computational analyses suggest that baculovirus GP64 superfamily proteins are class III penetrenes,http://dx.doi.org/10.1186/1743-422X-5-28,PMC2288602,18282283,CC BY,"BACKGROUND: Members of the Baculoviridae encode two types of proteins that mediate virus:cell membrane fusion and penetration into the host cell. Alignments of primary amino acid sequences indicate that baculovirus fusion proteins of group I nucleopolyhedroviruses (NPV) form the GP64 superfamily. The structure of these viral penetrenes has not been determined. The GP64 superfamily includes the glycoprotein (GP) encoded by members of the Thogotovirus genus of the Orthomyxoviridae. The entry proteins of other baculoviruses, group II NPV and granuloviruses, are class I penetrenes. RESULTS: Class III penetrenes encoded by members of the Rhabdoviridae and Herpesviridae have an internal fusion domain comprised of beta sheets, other beta sheet domains, an extended alpha helical domain, a membrane proximal stem domain and a carboxyl terminal anchor. Similar sequences and structural/functional motifs that characterize class III penetrenes are located collinearly in GP64 of group I baculoviruses and related glycoproteins encoded by thogotoviruses. Structural models based on a prototypic class III penetrene, vesicular stomatitis virus glycoprotein (VSV G), were established for Thogoto virus (THOV) GP and Autographa california multiple NPV (AcMNPV) GP64 demonstrating feasible cysteine linkages. Glycosylation sites in THOV GP and AcMNPV GP64 appear in similar model locations to the two glycosylation sites of VSV G. CONCLUSION: These results suggest that proteins in the GP64 superfamily are class III penetrenes.",2008 Feb 18,"['Garry, Courtney E', 'Garry, Robert F']",Virol J,,,True
6567692317d79659efda807e54ced960c8588ffb,PMC,Activation of Interleukin-32 Pro-Inflammatory Pathway in Response to Influenza A Virus Infection,http://dx.doi.org/10.1371/journal.pone.0001985,PMC2288676,18414668,CC BY,"BACKGROUND: Interleukin (IL)-32 is a recently described pro-inflammatory cytokine that has been reported to be induced by bacteria treatment in culture cells. Little is known about IL-32 production by exogenous pathogens infection in human individuals. METHODS AND FINDINGS: In this study, we found that IL-32 level was increased by 58.2% in the serum samples from a cohort of 108 patients infected by influenza A virus comparing to that of 115 healthy individuals. Another pro-inflammatory factor cyclooxygenase (COX)-2-associated prostaglandin E2 was also upregulated by 2.7-fold. Expression of IL-32 in influenza A virus infected A549 human lung epithelial cells was blocked by either selective COX-2 inhibitor NS398 or Aspirin, a known anti-inflammatory drug, indicating IL-32 was induced through COX-2 in the inflammatory cascade. Interestingly, we found that COX-2-associate PGE(2) production activated by influenza virus infection was significantly suppressed by over-expression of IL-32 but increased by IL-32-specific siRNA, suggesting there was a feedback mechanism between IL-32 and COX-2. CONCLUSIONS: IL-32 is induced by influenza A virus infection via COX-2 in the inflammatory cascade. Our results provide that IL-32 is a potential target for anti-inflammatory medicine screening.",2008 Apr 16,"['Li, Wei', 'Liu, Yan', 'Mukhtar, Muhammad Mahmood', 'Gong, Rui', 'Pan, Ying', 'Rasool, Sahibzada T.', 'Gao, Yecheng', 'Kang, Lei', 'Hao, Qian', 'Peng, Guiqing', 'Chen, Yanni', 'Chen, Xin', 'Wu, Jianguo', 'Zhu, Ying']",PLoS One,,,True
b61e1ca6b1b5a83aa20344e4832ac9ee1eb1dfa9,PMC,The Cuyahoga Is Still Burning,http://dx.doi.org/10.1289/ehp.11419,PMC2290999,18414602,CC0,,2008 Apr,"['Silbergeld, Ellen K.', 'Graham, Jay P.']",Environ Health Perspect,,,False
4e951550757b4a9f7b9b5167c9774a1113c787e9,PMC,Safety and immunogenicity of an MF59™-adjuvanted subunit influenza vaccine in elderly Chinese subjects,http://dx.doi.org/10.1186/1742-4933-5-2,PMC2291031,18289372,CC BY,"BACKGROUND: The safety and immunogenicity of an MF59™-adjuvanted subunit influenza vaccine (Sub/MF59™; FLUAD(®), Novartis Vaccines) was evaluated among elderly Chinese subjects (≥ 60 years of age). After a preliminary Phase I, open-label study (n = 25) to assess safety 1–14 days post-vaccination, a comparative observer-blind, randomised, controlled clinical trial (n = 600) was performed to assess safety and immunogenicity versus a non-adjuvanted subunit influenza vaccine (Subunit; Agrippal(®), Novartis Vaccines). Subjects were randomised (2:1) to receive Sub/MF59™ or Subunit. RESULTS: Both vaccines were well tolerated, with no vaccine-related serious adverse events reported during the Phase I trial. During the observer-blind study, local and systemic reactions were generally similar for both vaccines 1–22 days post-vaccination; however, injection-site induration was more frequent among the Subunit group (P < 0.05), and mild pain at the injection site and fever were more frequent among Sub/MF59™ recipients (P ≤ 0.005). Both vaccines induced a significant (P < 0.001) increase in geometric mean titres (GMTs) for the three strains tested, versus baseline; GMTs against A/H1N1, A/H3N2 and B were significantly higher in the Sub/MF59™ group (P = 0.034, P < 0.001 and P = 0.005, respectively). GMT ratios against A/H1N1, A/H3N2 and B were also significantly higher in the Sub/MF59™ group (P = 0.038, P < 0.001 and P = 0.006, respectively). Similarly, the percentage of subjects achieving seroprotection or seroconversion on Day 22 was greater for Sub/MF59™ recipients, reaching significance for A/H3N2 (P < 0.001). CONCLUSION: MF59™-adjuvanted subunit influenza vaccine is well tolerated by elderly Chinese subjects and induces a higher level of immunogenicity than a non-adjuvanted subunit influenza vaccine in this population that is at high risk of influenza-related complications. CLINICAL TRIAL REGISTRY: , NCT00310648",2008 Feb 20,"['Li, Rongcheng', 'Fang, Hanhua', 'Li, Yanping', 'Liu, Youping', 'Pellegrini, Michele', 'Podda, Audino']",Immun Ageing,,,True
5e9ccecdd40825f5c30da3a900fc5cf1b063b47d,PMC,Roles of TNF-α gene polymorphisms in the occurrence and progress of SARS-Cov infection: A case-control study,http://dx.doi.org/10.1186/1471-2334-8-27,PMC2291466,18312678,CC BY,"BACKGROUND: Host genetic factors may play a role in the occurrence and progress of SARS-Cov infection. This study was to investigate the relationship between tumor necrosis factor (TNF)-α gene polymorphisms with the occurrence of SARS-CoV infection and its role in prognosis of patients with lung interstitial fibrosis and femoral head osteonecrosis. METHODS: The association between genetic polymorphisms of TNF-α gene and susceptibility to severe acute respiratory syndromes (SARS) was conducted in a hospital-based case-control study including 75 SARS patients, 41 health care workers and 92 healthy controls. Relationships of TNF-α gene polymorphisms with interstitial lung fibrosis and femoral head osteonecrosis were carried out in two case-case studies in discharged SARS patients. PCR sequencing based typing (PCR-SBT) method was used to determine the polymorphisms of TNF-α gene in locus of the promoter region and univariate logistic analysis was conducted in analyzing the collected data. RESULTS: Compared to TT genotype, the CT genotype at the -204 locus was found associated with a protective effect on SARS with OR(95%CI) of 0.95(0.90–0.99). Also, TT genotype, CT and CC were found associated with a risk effect on femoral head necrosis with ORs(95%CI) of 5.33(1.39–20.45) and 5.67(2.74–11.71), respectively and the glucocorticoid adjusted OR of CT was 5.25(95%CI 1.18–23.46) and the combined (CT and CC) genotype OR was 6.0 (95%CI 1.60–22.55) at -1031 site of TNF-α gene. At the same time, the -863 AC genotype was manifested as another risk effect associated with femoral head necrosis with OR(95%CI) of 6.42(1.53–26.88) and the adjusted OR was 8.40(95%CI 1.76–40.02) in cured SARS patients compared to CC genotype. CONCLUSION: SNPs of TNF-α gene of promoter region may not associate with SARS-CoV infection. And these SNPs may not affect interstitial lung fibrosis in cured SARS patients. However, the -1031CT/CC and -863 AC genotypes may be risk factors of femoral head necrosis in discharged SARS patients.",2008 Feb 29,"['Wang, Shixin', 'Wei, Maoti', 'Han, Yi', 'Zhang, Keju', 'He, Li', 'Yang, Zhen', 'Su, Bing', 'Zhang, Zhilun', 'Hu, Yilan', 'Hui, Wuli']",BMC Infect Dis,,,True
6b18741fd5c6ab895acb11a559286c68b43eb9d4,PMC,Bioinformatics in China: A Personal Perspective,http://dx.doi.org/10.1371/journal.pcbi.1000020,PMC2291564,18437216,CC BY,,2008 Apr 25,"['Wei, Liping', 'Yu, Jun']",PLoS Comput Biol,,,True
f40d65d9dcb0b71bd266e62f77bc51d4c449eed1,PMC,The United States and Canada as a coupled epidemiological system: An example from hepatitis A,http://dx.doi.org/10.1186/1471-2334-8-23,PMC2292190,18307785,CC BY,"BACKGROUND: Hepatitis A (HA) is a low-incidence, non-endemic disease in Canada and the United States (US). However, a large difference in HA incidence between Canada and HA-endemic countries has made travel an important contributor to hepatitis A prevalence in Canada. There is also a (smaller) incidence differential between Canada and the US. Although the US has only moderately higher HA incidence, the volume of travel by Canadians to the US is many times higher than travel volume to endemic countries. Hence, travel to the US may constitute a source of low to moderate risk for Canadian travelers. To our knowledge, travel to the US has never been included as a potential risk factor for HA infection in Canadian epidemiologic analyses. The objective of this study was to use dynamic models to investigate the possible effects on hepatitis A incidence in Canada due to (1) implementing vaccination in the US, and (2) varying the volume of travel by Canadians to the US. METHODS: We developed and analyzed age-structured compartmental models for the transmission and vaccination of hepatitis A, for both Canada and the US. Models were parameterized using data on seroprevalence, case reporting, and travel patterns. The potential effect of hepatitis A prevalence in the US on hepatitis A prevalence in Canada was captured through a term representing infection of Canadians due to travel in the US. RESULTS: The model suggests that approximately 22% of HA cases in Canada in the mid 1990s may have been attributable to travel to the US. A universal vaccination programme that attained 70% coverage in young children in the US in the mid 1990s could have reduced Canadian incidence by 21% within 5 years. CONCLUSION: Since not all necessary data were available to parameterize the model, the results should be considered exploratory. However, the analysis shows that, under plausible assumptions, the US may be more important for determining HA prevalence in Canada than is currently supposed. As international travel continues to grow, making vaccination policies ever more relevant to populations beyond a country's borders, such multi-country models will most likely come into wider use as predictive aids for policy development.",2008 Feb 28,"['Amariei, Raluca', 'Willms, Allan R', 'Bauch, Chris T']",BMC Infect Dis,,,True
0e7e8aa9e5d952e8486bc9599764a9fcddd7f579,PMC,Improved production of human type II procollagen in the yeast Pichia pastoris in shake flasks by a wireless-controlled fed-batch system,http://dx.doi.org/10.1186/1472-6750-8-33,PMC2315644,18371201,CC BY,"BACKGROUND: Here we describe a new technical solution for optimization of Pichia pastoris shake flask cultures with the example of production of stable human type II collagen. Production of recombinant proteins in P. pastoris is usually performed by controlling gene expression with the strong AOX1 promoter, which is induced by addition of methanol. Optimization of processes using the AOX1 promoter in P. pastoris is generally done in bioreactors by fed-batch fermentation with a controlled continuous addition of methanol for avoiding methanol toxification and carbon/energy starvation. The development of feeding protocols and the study of AOX1-controlled recombinant protein production have been largely made in shake flasks, although shake flasks have very limited possibilities for measurement and control. RESULTS: By applying on-line pO(2 )monitoring we demonstrate that the widely used pulse feeding of methanol results in long phases of methanol exhaustion and consequently low expression of AOX1 controlled genes. Furthermore, we provide a solution to apply the fed-batch strategy in shake flasks. The presented solution applies a wireless feeding unit which can be flexibly positioned and allows the use of computer-controlled feeding profiles. By using the human collagen II as an example we show that a quasi-continuous feeding profile, being the simplest way of a fed-batch fermentation, results in a higher production level of human collagen II. Moreover, the product has a higher proteolytic stability compared to control cultures due to the increased expression of human collagen prolyl 4-hydroxylase as monitored by mRNA and protein levels. CONCLUSION: The recommended standard protocol for methanol addition in shake flasks using pulse feeding is non-optimal and leads to repeated long phases of methanol starvation. The problem can be solved by applying the fed-batch technology. The presented wireless feeding unit, together with an on-line monitoring system offers a flexible, simple, and low-cost solution for initial optimization of the production in shake flasks which can be performed in parallel. By this way the fed-batch strategy can be applied from the early screening steps also in laboratories which do not have access to high-cost and complicated bioreactor systems.",2008 Mar 27,"['Ruottinen, Maria', 'Bollok, Monika', 'Kögler, Martin', 'Neubauer, Antje', 'Krause, Mirja', 'Hämäläinen, Eija-Riitta', 'Myllyharju, Johanna', 'Vasala, Antti', 'Neubauer, Peter']",BMC Biotechnol,,,True
95beff3302bdaccd3ce824cdbf374a20b1a987b8,PMC,SARS-Coronavirus Replication/Transcription Complexes Are Membrane-Protected and Need a Host Factor for Activity In Vitro,http://dx.doi.org/10.1371/journal.ppat.1000054,PMC2322833,18451981,CC BY,"SARS-coronavirus (SARS-CoV) replication and transcription are mediated by a replication/transcription complex (RTC) of which virus-encoded, non-structural proteins (nsps) are the primary constituents. The 16 SARS-CoV nsps are produced by autoprocessing of two large precursor polyproteins. The RTC is believed to be associated with characteristic virus-induced double-membrane structures in the cytoplasm of SARS-CoV-infected cells. To investigate the link between these structures and viral RNA synthesis, and to dissect RTC organization and function, we isolated active RTCs from infected cells and used them to develop the first robust assay for their in vitro activity. The synthesis of genomic RNA and all eight subgenomic mRNAs was faithfully reproduced by the RTC in this in vitro system. Mainly positive-strand RNAs were synthesized and protein synthesis was not required for RTC activity in vitro. All RTC activity, enzymatic and putative membrane-spanning nsps, and viral RNA cosedimented with heavy membrane structures. Furthermore, the pelleted RTC required the addition of a cytoplasmic host factor for reconstitution of its in vitro activity. Newly synthesized subgenomic RNA appeared to be released, while genomic RNA remained predominantly associated with the RTC-containing fraction. RTC activity was destroyed by detergent treatment, suggesting an important role for membranes. The RTC appeared to be protected by membranes, as newly synthesized viral RNA and several replicase/transcriptase subunits were protease- and nuclease-resistant and became susceptible to degradation only upon addition of a non-ionic detergent. Our data establish a vital functional dependence of SARS-CoV RNA synthesis on virus-induced membrane structures.",2008 May 2,"['van Hemert, Martijn J.', 'van den Worm, Sjoerd H. E.', 'Knoops, Kèvin', 'Mommaas, A. Mieke', 'Gorbalenya, Alexander E.', 'Snijder, Eric J.']",PLoS Pathog,,,True
b281ffd13e1ca8492cc60ae608b6b24a7be46a1f,PMC,Methods for simultaneously identifying coherent local clusters with smooth global patterns in gene expression profiles,http://dx.doi.org/10.1186/1471-2105-9-155,PMC2322988,18366693,CC BY,"BACKGROUND: The hierarchical clustering tree (HCT) with a dendrogram [1] and the singular value decomposition (SVD) with a dimension-reduced representative map [2] are popular methods for two-way sorting the gene-by-array matrix map employed in gene expression profiling. While HCT dendrograms tend to optimize local coherent clustering patterns, SVD leading eigenvectors usually identify better global grouping and transitional structures. RESULTS: This study proposes a flipping mechanism for a conventional agglomerative HCT using a rank-two ellipse (R2E, an improved SVD algorithm for sorting purpose) seriation by Chen [3] as an external reference. While HCTs always produce permutations with good local behaviour, the rank-two ellipse seriation gives the best global grouping patterns and smooth transitional trends. The resulting algorithm automatically integrates the desirable properties of each method so that users have access to a clustering and visualization environment for gene expression profiles that preserves coherent local clusters and identifies global grouping trends. CONCLUSION: We demonstrate, through four examples, that the proposed method not only possesses better numerical and statistical properties, it also provides more meaningful biomedical insights than other sorting algorithms. We suggest that sorted proximity matrices for genes and arrays, in addition to the gene-by-array expression matrix, can greatly aid in the search for comprehensive understanding of gene expression structures. Software for the proposed methods can be obtained at .",2008 Mar 20,"['Tien, Yin-Jing', 'Lee, Yun-Shien', 'Wu, Han-Ming', 'Chen, Chun-Houh']",BMC Bioinformatics,,,True
46795b2f533aa0d3e20b1df752cf6c18455ad862,PMC,Pathogen Discovery,http://dx.doi.org/10.1371/journal.ppat.1000002,PMC2329853,18437241,CC BY,,2008 Apr 25,"Lipkin, W. Ian",PLoS Pathog,,,True
0e1c072b035756104151484e6548cac0517cc5f2,PMC,Synonym set extraction from the biomedical literature by lexical pattern discovery,http://dx.doi.org/10.1186/1471-2105-9-159,PMC2335115,18366721,CC BY,"BACKGROUND: Although there are a large number of thesauri for the biomedical domain many of them lack coverage in terms and their variant forms. Automatic thesaurus construction based on patterns was first suggested by Hearst [1], but it is still not clear how to automatically construct such patterns for different semantic relations and domains. In particular it is not certain which patterns are useful for capturing synonymy. The assumption of extant resources such as parsers is also a limiting factor for many languages, so it is desirable to find patterns that do not use syntactical analysis. Finally to give a more consistent and applicable result it is desirable to use these patterns to form synonym sets in a sound way. RESULTS: We present a method that automatically generates regular expression patterns by expanding seed patterns in a heuristic search and then develops a feature vector based on the occurrence of term pairs in each developed pattern. This allows for a binary classifications of term pairs as synonymous or non-synonymous. We then model this result as a probability graph to find synonym sets, which is equivalent to the well-studied problem of finding an optimal set cover. We achieved 73.2% precision and 29.7% recall by our method, out-performing hand-made resources such as MeSH and Wikipedia. CONCLUSION: We conclude that automatic methods can play a practical role in developing new thesauri or expanding on existing ones, and this can be done with only a small amount of training data and no need for resources such as parsers. We also concluded that the accuracy can be improved by grouping into synonym sets.",2008 Mar 24,"['McCrae, John', 'Collier, Nigel']",BMC Bioinformatics,,,True
5ed3b0cd33b9af56879a3b5f10d6b7399ae86785,PMC,Nanopolymers improve delivery of exon skipping oligonucleotides and concomitant dystrophin expression in skeletal muscle of mdx mice,http://dx.doi.org/10.1186/1472-6750-8-35,PMC2362111,18384691,CC BY,"BACKGROUND: Exon skipping oligonucleotides (ESOs) of 2'O-Methyl (2'OMe) and morpholino chemistry have been shown to restore dystrophin expression in muscle fibers from the mdx mouse, and are currently being tested in phase I clinical trials for Duchenne Muscular Dystrophy (DMD). However, ESOs remain limited in their effectiveness because of an inadequate delivery profile. Synthetic cationic copolymers of poly(ethylene imine) (PEI) and poly(ethylene glycol) (PEG) are regarded as effective agents for enhanced delivery of nucleic acids in various applications. RESULTS: We examined whether PEG-PEI copolymers can facilitate ESO-mediated dystrophin expression after intramuscular injections into tibialis anterior (TA) muscles of mdx mice. We utilized a set of PEG-PEI copolymers containing 2 kDa PEI and either 550 Da or 5 kDa PEG, both of which bind 2'OMe ESOs with high affinity and form stable nanoparticulates with a relatively low surface charge. Three weekly intramuscular injections of 5 μg of ESO complexed with PEI2K-PEG550 copolymers resulted in about 500 dystrophin-positive fibers and about 12% of normal levels of dystrophin expression at 3 weeks after the initial injection, which is significantly greater than for injections of ESO alone, which are known to be almost completely ineffective. In an effort to enhance biocompatibility and cellular uptake, the PEI2K-PEG550 and PEI2K-PEG5K copolymers were functionalized by covalent conjugation with nanogold (NG) or adsorbtion of colloidal gold (CG), respectively. Surprisingly, using the same injection and dosing regimen, we found no significant difference in dystrophin expression by Western blot between the NG-PEI2K-PEG550, CG-PEI2K-PEG5K, and non-functionalized PEI2K-PEG550 copolymers. Dose-response experiments using the CG-PEI2K-PEG5K copolymer with total ESO ranging from 3–60 μg yielded a maximum of about 15% dystrophin expression. Further improvements in dystrophin expression up to 20% of normal levels were found at 6 weeks after 10 twice-weekly injections of the NG-PEI2K-PEG550 copolymer complexed with 5 μg of ESO per injection. This injection and dosing regimen showed over 1000 dystrophin-positive fibers. H&E staining of all treated muscle groups revealed no overt signs of cytotoxicity. CONCLUSION: We conclude that PEGylated PEI2K copolymers are efficient carriers for local delivery of 2'OMe ESOs and warrant further development as potential therapeutics for treatment of DMD.",2008 Apr 2,"['Williams, Jason H', 'Schray, Rebecca C', 'Sirsi, Shashank R', 'Lutz, Gordon J']",BMC Biotechnol,,,True
702d0144bdeae0782bbebcbe41d432fa7ae41415,PMC,Functional Analysis of the 5′ Genomic Sequence of a Bovine Norovirus,http://dx.doi.org/10.1371/journal.pone.0002169,PMC2364642,18478070,CC BY,"BACKGROUND: Jena Virus (JV), a bovine Norovirus, causes enteric disease in cattle and represents a potential model for the study of enteric norovirus infection and pathogenesis. The positive sense RNA genome of JV is organised into ORF1 (non-structural proteins), ORF2 (major capsid protein) and ORF3 (minor capsid protein). The lack of a cell culture system for studying JV replication has meant that work to date has relied upon in vitro systems to study non-structural protein synthesis and processing. PRINCIPAL FINDINGS: Only two of the three major ORF1 proteins were identified (p110 and 2C) following in vitro translation of JV RNA, the N-term protein was not detected. The N-term encoding genomic sequence (5′GS) was tested for IRES-like function in a bi-cistronic system and displayed no evidence of IRES-like activity. The site of translation initiation in JV was determined to be at the predicted nucleotide 22. Following the insertion of an epitope within the 5′GS the JV N-term protein was identified in vitro and within RNA transfected cells. CONCLUSIONS: The in vitro transcription/translation system is currently the best system for analysing protein synthesis and processing in JV. Unlike similarly studied human noroviruses JV initially did not appear to express the N-terminal protein, presenting the possibility that the encoding RNA sequence had a regulatory function, most likely involved in translation initiation in an IRES-like manner. This was not the case and, following determination of the site of translation initiation the N-term protein was detected using an epitope tag, both in vitro and in vivo. Although slightly larger than predicted the N-term protein was detected in a processed form in vivo, thus not only demonstrating initial translation of the ORF1 polyprotein but also activity of the viral protease. These findings indicate that the block to noroviral replication in cultured cells lies elsewhere.",2008 May 14,"['Salim, Omar', 'Clarke, Ian N.', 'Lambden, Paul R.']",PLoS One,,,True
d94115064a8168415d634f654869a4009e4c3c70,PMC,Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households,http://dx.doi.org/10.1371/journal.pone.0002101,PMC2364646,18461182,CC0,"BACKGROUND: There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza. We implemented a study of the feasibility and efficacy of face masks and hand hygiene to reduce influenza transmission among Hong Kong household members. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cluster randomized controlled trial of households (composed of at least 3 members) where an index subject presented with influenza-like-illness of <48 hours duration. After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test, the household of the index subject was randomized to 1) control or 2) surgical face masks or 3) hand hygiene. Households were visited within 36 hours, and 3, 6 and 9 days later. Nose and throat swabs were collected from index subjects and all household contacts at each home visit and tested by viral culture. The primary outcome measure was laboratory culture confirmed influenza in a household contact; the secondary outcome was clinically diagnosed influenza (by self-reported symptoms). We randomized 198 households and completed follow up home visits in 128; the index cases in 122 of those households had laboratory-confirmed influenza. There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6%. Clinical secondary attack ratios varied from 5% to 18% depending on case definitions. The laboratory-based or clinical secondary attack ratios did not significantly differ across the intervention arms. Adherence to interventions was variable. CONCLUSIONS/SIGNIFICANCE: The secondary attack ratios were lower than anticipated, and lower than reported in other countries, perhaps due to differing patterns of susceptibility, lack of significant antigenic drift in circulating influenza virus strains recently, and/or issues related to the symptomatic recruitment design. Lessons learnt from this pilot have informed changes for the main study in 2008. TRIAL REGISTRATION: ClinicalTrials.gov NCT00425893 HKClinicalTrials.com HKCTR-365",2008 May 7,"['Cowling, Benjamin J.', 'Fung, Rita O. P.', 'Cheng, Calvin K. Y.', 'Fang, Vicky J.', 'Chan, Kwok Hung', 'Seto, Wing Hong', 'Yung, Raymond', 'Chiu, Billy', 'Lee, Paco', 'Uyeki, Timothy M.', 'Houck, Peter M.', 'Peiris, J. S. Malik', 'Leung, Gabriel M.']",PLoS One,,,True
3d2962558f0a2ed4ddc00989168efe60856bd792,PMC,Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households,http://dx.doi.org/10.1371/journal.pone.0002101,PMC2364646,18461182,CC0,"BACKGROUND: There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza. We implemented a study of the feasibility and efficacy of face masks and hand hygiene to reduce influenza transmission among Hong Kong household members. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cluster randomized controlled trial of households (composed of at least 3 members) where an index subject presented with influenza-like-illness of <48 hours duration. After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test, the household of the index subject was randomized to 1) control or 2) surgical face masks or 3) hand hygiene. Households were visited within 36 hours, and 3, 6 and 9 days later. Nose and throat swabs were collected from index subjects and all household contacts at each home visit and tested by viral culture. The primary outcome measure was laboratory culture confirmed influenza in a household contact; the secondary outcome was clinically diagnosed influenza (by self-reported symptoms). We randomized 198 households and completed follow up home visits in 128; the index cases in 122 of those households had laboratory-confirmed influenza. There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6%. Clinical secondary attack ratios varied from 5% to 18% depending on case definitions. The laboratory-based or clinical secondary attack ratios did not significantly differ across the intervention arms. Adherence to interventions was variable. CONCLUSIONS/SIGNIFICANCE: The secondary attack ratios were lower than anticipated, and lower than reported in other countries, perhaps due to differing patterns of susceptibility, lack of significant antigenic drift in circulating influenza virus strains recently, and/or issues related to the symptomatic recruitment design. Lessons learnt from this pilot have informed changes for the main study in 2008. TRIAL REGISTRATION: ClinicalTrials.gov NCT00425893 HKClinicalTrials.com HKCTR-365",2008 May 7,"['Cowling, Benjamin J.', 'Fung, Rita O. P.', 'Cheng, Calvin K. Y.', 'Fang, Vicky J.', 'Chan, Kwok Hung', 'Seto, Wing Hong', 'Yung, Raymond', 'Chiu, Billy', 'Lee, Paco', 'Uyeki, Timothy M.', 'Houck, Peter M.', 'Peiris, J. S. Malik', 'Leung, Gabriel M.']",PLoS One,,,True
eed4a68d4e44f9887b3219ad5813eed5f0c4d42b,PMC,Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households,http://dx.doi.org/10.1371/journal.pone.0002101,PMC2364646,18461182,CC0,"BACKGROUND: There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza. We implemented a study of the feasibility and efficacy of face masks and hand hygiene to reduce influenza transmission among Hong Kong household members. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cluster randomized controlled trial of households (composed of at least 3 members) where an index subject presented with influenza-like-illness of <48 hours duration. After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test, the household of the index subject was randomized to 1) control or 2) surgical face masks or 3) hand hygiene. Households were visited within 36 hours, and 3, 6 and 9 days later. Nose and throat swabs were collected from index subjects and all household contacts at each home visit and tested by viral culture. The primary outcome measure was laboratory culture confirmed influenza in a household contact; the secondary outcome was clinically diagnosed influenza (by self-reported symptoms). We randomized 198 households and completed follow up home visits in 128; the index cases in 122 of those households had laboratory-confirmed influenza. There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6%. Clinical secondary attack ratios varied from 5% to 18% depending on case definitions. The laboratory-based or clinical secondary attack ratios did not significantly differ across the intervention arms. Adherence to interventions was variable. CONCLUSIONS/SIGNIFICANCE: The secondary attack ratios were lower than anticipated, and lower than reported in other countries, perhaps due to differing patterns of susceptibility, lack of significant antigenic drift in circulating influenza virus strains recently, and/or issues related to the symptomatic recruitment design. Lessons learnt from this pilot have informed changes for the main study in 2008. TRIAL REGISTRATION: ClinicalTrials.gov NCT00425893 HKClinicalTrials.com HKCTR-365",2008 May 7,"['Cowling, Benjamin J.', 'Fung, Rita O. P.', 'Cheng, Calvin K. Y.', 'Fang, Vicky J.', 'Chan, Kwok Hung', 'Seto, Wing Hong', 'Yung, Raymond', 'Chiu, Billy', 'Lee, Paco', 'Uyeki, Timothy M.', 'Houck, Peter M.', 'Peiris, J. S. Malik', 'Leung, Gabriel M.']",PLoS One,,,True
af1eb3ba403f1baa08d494a446fab866d82e69d9,PMC,Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households,http://dx.doi.org/10.1371/journal.pone.0002101,PMC2364646,18461182,CC0,"BACKGROUND: There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza. We implemented a study of the feasibility and efficacy of face masks and hand hygiene to reduce influenza transmission among Hong Kong household members. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cluster randomized controlled trial of households (composed of at least 3 members) where an index subject presented with influenza-like-illness of <48 hours duration. After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test, the household of the index subject was randomized to 1) control or 2) surgical face masks or 3) hand hygiene. Households were visited within 36 hours, and 3, 6 and 9 days later. Nose and throat swabs were collected from index subjects and all household contacts at each home visit and tested by viral culture. The primary outcome measure was laboratory culture confirmed influenza in a household contact; the secondary outcome was clinically diagnosed influenza (by self-reported symptoms). We randomized 198 households and completed follow up home visits in 128; the index cases in 122 of those households had laboratory-confirmed influenza. There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6%. Clinical secondary attack ratios varied from 5% to 18% depending on case definitions. The laboratory-based or clinical secondary attack ratios did not significantly differ across the intervention arms. Adherence to interventions was variable. CONCLUSIONS/SIGNIFICANCE: The secondary attack ratios were lower than anticipated, and lower than reported in other countries, perhaps due to differing patterns of susceptibility, lack of significant antigenic drift in circulating influenza virus strains recently, and/or issues related to the symptomatic recruitment design. Lessons learnt from this pilot have informed changes for the main study in 2008. TRIAL REGISTRATION: ClinicalTrials.gov NCT00425893 HKClinicalTrials.com HKCTR-365",2008 May 7,"['Cowling, Benjamin J.', 'Fung, Rita O. P.', 'Cheng, Calvin K. Y.', 'Fang, Vicky J.', 'Chan, Kwok Hung', 'Seto, Wing Hong', 'Yung, Raymond', 'Chiu, Billy', 'Lee, Paco', 'Uyeki, Timothy M.', 'Houck, Peter M.', 'Peiris, J. S. Malik', 'Leung, Gabriel M.']",PLoS One,,,False
45413d24ce4a3a305bd77754c506c525d308396b,PMC,Real Time Bayesian Estimation of the Epidemic Potential of Emerging Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0002185,PMC2366072,18478118,CC BY,"BACKGROUND: Fast changes in human demographics worldwide, coupled with increased mobility, and modified land uses make the threat of emerging infectious diseases increasingly important. Currently there is worldwide alert for H5N1 avian influenza becoming as transmissible in humans as seasonal influenza, and potentially causing a pandemic of unprecedented proportions. Here we show how epidemiological surveillance data for emerging infectious diseases can be interpreted in real time to assess changes in transmissibility with quantified uncertainty, and to perform running time predictions of new cases and guide logistics allocations. METHODOLOGY/PRINCIPAL FINDINGS: We develop an extension of standard epidemiological models, appropriate for emerging infectious diseases, that describes the probabilistic progression of case numbers due to the concurrent effects of (incipient) human transmission and multiple introductions from a reservoir. The model is cast in terms of surveillance observables and immediately suggests a simple graphical estimation procedure for the effective reproductive number R (mean number of cases generated by an infectious individual) of standard epidemics. For emerging infectious diseases, which typically show large relative case number fluctuations over time, we develop a Bayesian scheme for real time estimation of the probability distribution of the effective reproduction number and show how to use such inferences to formulate significance tests on future epidemiological observations. CONCLUSIONS/SIGNIFICANCE: Violations of these significance tests define statistical anomalies that may signal changes in the epidemiology of emerging diseases and should trigger further field investigation. We apply the methodology to case data from World Health Organization reports to place bounds on the current transmissibility of H5N1 influenza in humans and establish a statistical basis for monitoring its evolution in real time.",2008 May 14,"['Bettencourt, Luís M. A.', 'Ribeiro, Ruy M.']",PLoS One,,,True
2000b56ab7a60199d3bbb2148295370ae87b3d58,PMC,Real Time Bayesian Estimation of the Epidemic Potential of Emerging Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0002185,PMC2366072,18478118,CC BY,"BACKGROUND: Fast changes in human demographics worldwide, coupled with increased mobility, and modified land uses make the threat of emerging infectious diseases increasingly important. Currently there is worldwide alert for H5N1 avian influenza becoming as transmissible in humans as seasonal influenza, and potentially causing a pandemic of unprecedented proportions. Here we show how epidemiological surveillance data for emerging infectious diseases can be interpreted in real time to assess changes in transmissibility with quantified uncertainty, and to perform running time predictions of new cases and guide logistics allocations. METHODOLOGY/PRINCIPAL FINDINGS: We develop an extension of standard epidemiological models, appropriate for emerging infectious diseases, that describes the probabilistic progression of case numbers due to the concurrent effects of (incipient) human transmission and multiple introductions from a reservoir. The model is cast in terms of surveillance observables and immediately suggests a simple graphical estimation procedure for the effective reproductive number R (mean number of cases generated by an infectious individual) of standard epidemics. For emerging infectious diseases, which typically show large relative case number fluctuations over time, we develop a Bayesian scheme for real time estimation of the probability distribution of the effective reproduction number and show how to use such inferences to formulate significance tests on future epidemiological observations. CONCLUSIONS/SIGNIFICANCE: Violations of these significance tests define statistical anomalies that may signal changes in the epidemiology of emerging diseases and should trigger further field investigation. We apply the methodology to case data from World Health Organization reports to place bounds on the current transmissibility of H5N1 influenza in humans and establish a statistical basis for monitoring its evolution in real time.",2008 May 14,"['Bettencourt, Luís M. A.', 'Ribeiro, Ruy M.']",PLoS One,,,True
7a5478dfe79fbf67551ac9261f190d899ba719b3,PMC,IL-12 RB1 Genetic Variants Contribute to Human Susceptibility to Severe Acute Respiratory Syndrome Infection among Chinese,http://dx.doi.org/10.1371/journal.pone.0002183,PMC2367437,18478121,CC BY,"BACKGROUND: Cytokines play important roles in antiviral action. We examined whether polymorphisms of interleukin (IL)-12 receptor B1 (IL-12RB1) affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). METHODS: A case-control study was carried out in Chinese SARS patients and healthy controls. The genotypes of 4SNPs on IL-12 RB1 gene, +705A/G,+1158T/C, +1196G/C and +1664 C/T, were determined by PCR-RFLP. Haplotypes were estimated from the genotype data using the expectation-maximisation algorithm. RESULTS: Comparison between patients and close contacts showed that individuals with the +1664 C/T (CT and TT) genotype had a 2.09-fold (95% confidence interval [CI], 1.90–7.16) and 2.34-fold (95% CI, 1.79–13.37) increased risk of developing SARS, respectively. For any of the other three polymorphisms, however, no significant difference can be detected in allele or genotype frequencies between patients and controls. Additionally, estimation of the frequencies of multiple-locus haplotypes revealed potential risk haplotypes (GCCT) for SARS infection. CONCLUSIONS: Our data indicate that genetic variants of IL12RB1confer genetic susceptibility to SARS infection, but not necessary associated with the progression of the disease in Chinese population.",2008 May 14,"['Tang, Fang', 'Liu, Wei', 'Zhang, Fang', 'Xin, Zhong-Tao', 'Wei, Mao-Ti', 'Zhang, Pan-He', 'Yang, Hong', 'Ly, Hinh', 'Cao, Wu-Chun']",PLoS One,,,True
92ed9b003b6c24304a7bad059d22c286735ed839,PMC,"DetectiV: visualization, normalization and significance testing for pathogen-detection microarray data",http://dx.doi.org/10.1186/gb-2007-8-9-r190,PMC2375028,17868443,CC BY,"DNA microarrays offer the possibility of testing for the presence of thousands of micro-organisms in a single experiment. However, there is a lack of reliable bioinformatics tools for the analysis of such data. We have developed DetectiV, a package for the statistical software R. DetectiV offers powerful yet simple visualization, normalization and significance testing tools. We show that DetectiV performs better than previously published software on a large, publicly available dataset.",2007 Sep 14,"['Watson, Michael', 'Dukes, Juliet', 'Abu-Median, Abu-Bakr', 'King, Donald P', 'Britton, Paul']",Genome Biol,,,True
857137889eef45edb1a66c1950f0e0ca27ad63a4,PMC,Viral Control of Mitochondrial Apoptosis,http://dx.doi.org/10.1371/journal.ppat.1000018,PMC2376094,18516228,CC BY,"Throughout the process of pathogen–host co-evolution, viruses have developed a battery of distinct strategies to overcome biochemical and immunological defenses of the host. Thus, viruses have acquired the capacity to subvert host cell apoptosis, control inflammatory responses, and evade immune reactions. Since the elimination of infected cells via programmed cell death is one of the most ancestral defense mechanisms against infection, disabling host cell apoptosis might represent an almost obligate step in the viral life cycle. Conversely, viruses may take advantage of stimulating apoptosis, either to kill uninfected cells from the immune system, or to induce the breakdown of infected cells, thereby favoring viral dissemination. Several viral polypeptides are homologs of host-derived apoptosis-regulatory proteins, such as members of the Bcl-2 family. Moreover, viral factors with no homology to host proteins specifically target key components of the apoptotic machinery. Here, we summarize the current knowledge on the viral modulation of mitochondrial apoptosis, by focusing in particular on the mechanisms by which viral proteins control the host cell death apparatus.",2008 May 30,"['Galluzzi, Lorenzo', 'Brenner, Catherine', 'Morselli, Eugenia', 'Touat, Zahia', 'Kroemer, Guido']",PLoS Pathog,,,True
235855da90347b259f4d6b244821f3c1c264c04e,PMC,Expression of Foot-and-Mouth Disease Virus Capsid Proteins in Silkworm-Baculovirus Expression System and Its Utilization as a Subunit Vaccine,http://dx.doi.org/10.1371/journal.pone.0002273,PMC2386233,18509464,CC BY,"BACKGROUND: Foot-and-mouth disease (FMD) is a highly contagious disease of livestock that causes severe economic loss in susceptible cloven-hoofed animals. Although the traditional inactivated vaccine has been proved effective, it may lead to a new outbreak of FMD because of either incomplete inactivation of FMDV or the escape of live virus from vaccine production workshop. Thus, it is urgent to develop a novel FMDV vaccine that is safer, more effective and more economical than traditional vaccines. METHODOLOGY AND PRINCIPAL FINDINGS: A recombinant silkworm baculovirus Bm-P12A3C which contained the intact P1-2A and 3C protease coding regions of FMDV Asia 1/HNK/CHA/05 was developed. Indirect immunofluorescence test and sandwich-ELISA were used to verify that Bm-P12A3C could express the target cassette. Expression products from silkworm were diluted to 30 folds and used as antigen to immunize cattle. Specific antibody was induced in all vaccinated animals. After challenge with virulent homologous virus, four of the five animals were completely protected, and clinical symptoms were alleviated and delayed in the remaining one. Furthermore, a PD(50) (50% bovine protective dose) test was performed to assess the bovine potency of the subunit vaccine. The result showed the subunit vaccine could achieve 6.34 PD(50) per dose. CONCLUSION: The results suggest that this strategy might be used to develop the new subunit FMDV vaccine.",2008 May 28,"['Li, Zhiyong', 'Yi, Yongzhu', 'Yin, Xiangping', 'Zhang, Zhifang', 'Liu, Jixing']",PLoS One,,,True
b67b75854801b20d8d89d71adf85199ec70c3daa,PMC,A flexibly shaped space-time scan statistic for disease outbreak detection and monitoring,http://dx.doi.org/10.1186/1476-072X-7-14,PMC2386448,18402711,CC BY,"BACKGROUND: Early detection of disease outbreaks enables public health officials to implement disease control and prevention measures at the earliest possible time. A time periodic geographical disease surveillance system based on a cylindrical space-time scan statistic has been used extensively for disease surveillance along with the SaTScan software. In the purely spatial setting, many different methods have been proposed to detect spatial disease clusters. In particular, some spatial scan statistics are aimed at detecting irregularly shaped clusters which may not be detected by the circular spatial scan statistic. RESULTS: Based on the flexible purely spatial scan statistic, we propose a flexibly shaped space-time scan statistic for early detection of disease outbreaks. The performance of the proposed space-time scan statistic is compared with that of the cylindrical scan statistic using benchmark data. In order to compare their performances, we have developed a space-time power distribution by extending the purely spatial bivariate power distribution. Daily syndromic surveillance data in Massachusetts, USA, are used to illustrate the proposed test statistic. CONCLUSION: The flexible space-time scan statistic is well suited for detecting and monitoring disease outbreaks in irregularly shaped areas.",2008 Apr 11,"['Takahashi, Kunihiko', 'Kulldorff, Martin', 'Tango, Toshiro', 'Yih, Katherine']",Int J Health Geogr,,,True
3f6a8fc2249ec3b9bc431c5eded7f6234c75c49d,PMC,The effect of network mixing patterns on epidemic dynamics and the efficacy of disease contact tracing,http://dx.doi.org/10.1098/rsif.2007.1272,PMC2386895,18055417,CC BY,"In networks, nodes may preferentially contact other nodes with similar (assortatively mixed) or dissimilar (disassortatively mixed) numbers of contacts. Different patterns of contact support different epidemic dynamics, potentially affecting the efficacy of control measures such as contact tracing, which aims to identify and isolate nodes with infectious contacts. We used stochastic simulations to investigate the effects of mixing patterns on epidemic dynamics and contact-tracing efficacy. For uncontrolled epidemics, outbreaks occur at lower infection rates for more assortatively mixed networks, with faster initial epidemic growth rate and shorter epidemic duration than for disassortatively mixed networks. Contact tracing performs better for assortative mixing where epidemic size is large and tracing rate low, but it performs better for disassortative mixing at higher contact rates. For assortatively mixed networks, disease spreads first to highly connected nodes, but this is balanced by contact tracing quickly identifying these same nodes. The converse is true for disassortative mixing, where both disease and tracing are less likely to target highly connected nodes. For small epidemics, contact tracing is more effective on disassortative networks due to the greater resilience of assortative networks to link removal. Multi-step contact tracing is more effective than single-step tracing for assortative mixing, but this effect is smaller for disassortatively mixed networks.",2008 Jul 6,"['Kiss, Istvan Z', 'Green, Darren M', 'Kao, Rowland R']",J R Soc Interface,,,True
646484c8081b3f1bf336bae89411c2aa86885788,PMC,General Practice and Pandemic Influenza: A Framework for Planning and Comparison of Plans in Five Countries,http://dx.doi.org/10.1371/journal.pone.0002269,PMC2386973,18509538,CC BY,"BACKGROUND: Although primary health care, and in particular, general practice will be at the frontline in the response to pandemic influenza, there are no frameworks to guide systematic planning for this task or to appraise available plans for their relevance to general practice. We aimed to develop a framework that will facilitate planning for general practice, and used it to appraise pandemic plans from Australia, England, USA, New Zealand and Canada. METHODOLOGY/PRINCIPAL FINDINGS: We adapted the Haddon matrix to develop the framework, populating its cells through a multi-method study that incorporated the peer-reviewed and grey literature, interviews with general practitioners, practice nurses and senior decision-makers, and desktop simulation exercises. We used the framework to analyse 89 publicly-available jurisdictional plans at similar managerial levels in the five countries. The framework identifies four functional domains: clinical care for influenza and other needs, public health responsibilities, the internal environment and the macro-environment of general practice. No plan addressed all four domains. Most plans either ignored or were sketchy about non-influenza clinical needs, and about the contribution of general practice to public health beyond surveillance. Collaborations between general practices were addressed in few plans, and inter-relationships with the broader health system, even less frequently. CONCLUSIONS: This is the first study to provide a framework to guide general practice planning for pandemic influenza. The framework helped identify critical shortcomings in available plans. Engaging general practice effectively in planning is challenging, particularly where governance structures for primary health care are weak. We identify implications for practice and for research.",2008 May 28,"['Patel, Mahomed S.', 'Phillips, Christine B.', 'Pearce, Christopher', 'Kljakovic, Marjan', 'Dugdale, Paul', 'Glasgow, Nicholas']",PLoS One,,,True
f080c95434a5112c5e2da4e3f93131fed6207fe7,PMC,"Gene expression analyses in Atlantic salmon challenged with infectious salmon anemia virus reveal differences between individuals with early, intermediate and late mortality",http://dx.doi.org/10.1186/1471-2164-9-179,PMC2387173,18423000,CC BY,"BACKGROUND: Infectious salmon anemia virus (ISAV) causes a multisystemic disease responsible for severe losses in salmon aquaculture. Better understanding of factors that explain variations in resistance between individuals and families is essential for development of strategies for disease control. To approach this, we compared global gene expression using microarrays in fish dying early and late in the time course following infection from a highly pathogenic ISAV. RESULTS: Tissues (gill, heart, liver and spleen) from infected Atlantic salmon (cohabitation, ISAV Glesvaer 2/90 isolate) were collected from three stages over the time course of the experiment; early (EM, 0–10% cumulative mortality (CM), 21–25 days post-infection (DPI)), intermediate (IM, 35–55% CM, 28–31 DPI) and late (LM, 75–85% CM, 37–48 DPI) mortality. Viral loads were equal in EM and IM but dropped markedly in LM fish. Gene expression analyses using a 1.8 K salmonid fish cDNA microarray (SFA2.0) and real-time qPCR revealed a large group of genes highly up-regulated across tissues in EM, which were mainly implicated in innate antiviral responses and cellular stress. Despite equal levels of MHC class I in EM and LM, increase of splenic and cardiac expression of immunoglobulin-like genes was found only in LM while a suite of adaptive immunity markers were activated already in IM. The hepatic responses to ISAV were characterized by difference between EM and LM in expression of chaperones and genes involved in eicosanoid metabolism. To develop classification of high and low resistance phenotypes based on a small number of genes, we processed results from qPCR analyses of liver using a linear discriminant analysis. Four genes (5-lipoxygenase activating protein, cytochrome P450 2K4-1, galectin-9 and annexin A1) were sufficient for correct assignment of individuals to EM, LM and uninfected groups, while IM was inseparable from EM. Three of four prognostic markers are involved in metabolism of inflammatory regulators. CONCLUSION: This study adds to the understanding of molecular determinants for resistance to acute ISAV infection. The most susceptible individuals were characterized by high viral replication and dramatic activation of innate immune responses, which did not provide protection. The ability to endure high levels of infection for sustained periods could be associated with lower inflammatory responses while subsequent protection and viral clearance was most likely conferred by activation of adaptive immunity.",2008 Apr 18,"['Jørgensen, Sven Martin', 'Afanasyev, Sergey', 'Krasnov, Aleksei']",BMC Genomics,,,True
578d296ec1f6acc01c08cc5a9861bac6d47ddfda,PMC,Cellular Proteins in Influenza Virus Particles,http://dx.doi.org/10.1371/journal.ppat.1000085,PMC2390764,18535660,CC BY,"Virions are thought to contain all the essential proteins that govern virus egress from the host cell and initiation of replication in the target cell. It has been known for some time that influenza virions contain nine viral proteins; however, analyses of other enveloped viruses have revealed that proteins from the host cell can also be detected in virions. To address whether the same is true for influenza virus, we used two complementary mass spectrometry approaches to perform a comprehensive proteomic analysis of purified influenza virus particles. In addition to the aforementioned nine virus-encoded proteins, we detected the presence of 36 host-encoded proteins. These include both cytoplasmic and membrane-bound proteins that can be grouped into several functional categories, such as cytoskeletal proteins, annexins, glycolytic enzymes, and tetraspanins. Interestingly, a significant number of these have also been reported to be present in virions of other virus families. Protease treatment of virions combined with immunoblot analysis was used to verify the presence of the cellular protein and also to determine whether it is located in the core of the influenza virus particle. Immunogold labeling confirmed the presence of membrane-bound host proteins on the influenza virus envelope. The identification of cellular constituents of influenza virions has important implications for understanding the interactions of influenza virus with its host and brings us a step closer to defining the cellular requirements for influenza virus replication. While not all of the host proteins are necessarily incorporated specifically, those that are and are found to have an essential role represent novel targets for antiviral drugs and for attenuation of viruses for vaccine purposes.",2008 Jun 6,"['Shaw, Megan L.', 'Stone, Kathryn L.', 'Colangelo, Christopher M.', 'Gulcicek, Erol E.', 'Palese, Peter']",PLoS Pathog,,,True
4cd8e92fcab8da2c840ff39f14ca35bf5ba6e444,PMC,Graphical presentation of diagnostic information,http://dx.doi.org/10.1186/1471-2288-8-20,PMC2394529,18405357,CC BY,"BACKGROUND: Graphical displays of results allow researchers to summarise and communicate the key findings of their study. Diagnostic information should be presented in an easily interpretable way, which conveys both test characteristics (diagnostic accuracy) and the potential for use in clinical practice (predictive value). METHODS: We discuss the types of graphical display commonly encountered in primary diagnostic accuracy studies and systematic reviews of such studies, and systematically review the use of graphical displays in recent diagnostic primary studies and systematic reviews. RESULTS: We identified 57 primary studies and 49 systematic reviews. Fifty-six percent of primary studies and 53% of systematic reviews used graphical displays to present results. Dot-plot or box-and- whisker plots were the most commonly used graph in primary studies and were included in 22 (39%) studies. ROC plots were the most common type of plot included in systematic reviews and were included in 22 (45%) reviews. One primary study and five systematic reviews included a probability-modifying plot. CONCLUSION: Graphical displays are currently underused in primary diagnostic accuracy studies and systematic reviews of such studies. Diagnostic accuracy studies need to include multiple types of graphic in order to provide both a detailed overview of the results (diagnostic accuracy) and to communicate information that can be used to inform clinical practice (predictive value). Work is required to improve graphical displays, to better communicate the utility of a test in clinical practice and the implications of test results for individual patients.",2008 Apr 11,"['Whiting, Penny F', 'Sterne, Jonathan AC', 'Westwood, Marie E', 'Bachmann, Lucas M', 'Harbord, Roger', 'Egger, Matthias', 'Deeks, Jonathan J']",BMC Med Res Methodol,,,True
b04df94d885c540b1a5adba12f6fb402e9a09b0c,PMC,Improved microarray gene expression profiling of virus-infected cells after removal of viral RNA,http://dx.doi.org/10.1186/1471-2164-9-221,PMC2397413,18479515,CC BY,"BACKGROUND: Sensitivity and accuracy are key points when using microarrays to detect alterations in gene expression under different conditions. Critical to the acquisition of reliable results is the preparation of the RNA. In the field of virology, when analyzing the host cell's reaction to infection, the often high representation of viral RNA (vRNA) within total RNA preparations from infected cells is likely to interfere with microarray analysis. Yet, this effect has not been investigated despite the many reports that describe gene expression profiling of virus-infected cells using microarrays. RESULTS: In this study we used coronaviruses as a model to show that vRNA indeed interferes with microarray analysis, decreasing both sensitivity and accuracy. We also demonstrate that the removal of vRNA from total RNA samples, by means of virus-specific oligonucleotide capturing, significantly reduced the number of false-positive hits and increased the sensitivity of the method as tested on different array platforms. CONCLUSION: We therefore recommend the specific removal of vRNA, or of any other abundant 'contaminating' RNAs, from total RNA samples to improve the quality and reliability of microarray analyses.",2008 May 14,"['Raaben, Matthijs', 'Whitley, Penn', 'Bouwmeester, Diane', 'Setterquist, Robert A', 'Rottier, Peter JM', 'de Haan, Cornelis AM']",BMC Genomics,,,True
c36cd2c280cc73cdb747ef5c6058b3657859c767,PMC,Improved microarray gene expression profiling of virus-infected cells after removal of viral RNA,http://dx.doi.org/10.1186/1471-2164-9-221,PMC2397413,18479515,CC BY,"BACKGROUND: Sensitivity and accuracy are key points when using microarrays to detect alterations in gene expression under different conditions. Critical to the acquisition of reliable results is the preparation of the RNA. In the field of virology, when analyzing the host cell's reaction to infection, the often high representation of viral RNA (vRNA) within total RNA preparations from infected cells is likely to interfere with microarray analysis. Yet, this effect has not been investigated despite the many reports that describe gene expression profiling of virus-infected cells using microarrays. RESULTS: In this study we used coronaviruses as a model to show that vRNA indeed interferes with microarray analysis, decreasing both sensitivity and accuracy. We also demonstrate that the removal of vRNA from total RNA samples, by means of virus-specific oligonucleotide capturing, significantly reduced the number of false-positive hits and increased the sensitivity of the method as tested on different array platforms. CONCLUSION: We therefore recommend the specific removal of vRNA, or of any other abundant 'contaminating' RNAs, from total RNA samples to improve the quality and reliability of microarray analyses.",2008 May 14,"['Raaben, Matthijs', 'Whitley, Penn', 'Bouwmeester, Diane', 'Setterquist, Robert A', 'Rottier, Peter JM', 'de Haan, Cornelis AM']",BMC Genomics,,,False
a6748cf5afbb792757eb09e822f8f2d49cd127b5,PMC,Improved microarray gene expression profiling of virus-infected cells after removal of viral RNA,http://dx.doi.org/10.1186/1471-2164-9-221,PMC2397413,18479515,CC BY,"BACKGROUND: Sensitivity and accuracy are key points when using microarrays to detect alterations in gene expression under different conditions. Critical to the acquisition of reliable results is the preparation of the RNA. In the field of virology, when analyzing the host cell's reaction to infection, the often high representation of viral RNA (vRNA) within total RNA preparations from infected cells is likely to interfere with microarray analysis. Yet, this effect has not been investigated despite the many reports that describe gene expression profiling of virus-infected cells using microarrays. RESULTS: In this study we used coronaviruses as a model to show that vRNA indeed interferes with microarray analysis, decreasing both sensitivity and accuracy. We also demonstrate that the removal of vRNA from total RNA samples, by means of virus-specific oligonucleotide capturing, significantly reduced the number of false-positive hits and increased the sensitivity of the method as tested on different array platforms. CONCLUSION: We therefore recommend the specific removal of vRNA, or of any other abundant 'contaminating' RNAs, from total RNA samples to improve the quality and reliability of microarray analyses.",2008 May 14,"['Raaben, Matthijs', 'Whitley, Penn', 'Bouwmeester, Diane', 'Setterquist, Robert A', 'Rottier, Peter JM', 'de Haan, Cornelis AM']",BMC Genomics,,,False
4ace931a12cf4c36b131fcf16b49bf36eb15f8e3,PMC,Virus Adaptation by Manipulation of Host's Gene Expression,http://dx.doi.org/10.1371/journal.pone.0002397,PMC2398778,18545680,CC BY,"Viruses adapt to their hosts by evading defense mechanisms and taking over cellular metabolism for their own benefit. Alterations in cell metabolism as well as side-effects of antiviral responses contribute to symptoms development and virulence. Sometimes, a virus may spill over from its usual host species into a novel one, where usually will fail to successfully infect and further transmit to new host. However, in some cases, the virus transmits and persists after fixing beneficial mutations that allow for a better exploitation of the new host. This situation would represent a case for a new emerging virus. Here we report results from an evolution experiment in which a plant virus was allowed to infect and evolve on a naïve host. After 17 serial passages, the viral genome has accumulated only five changes, three of which were non-synonymous. An amino acid substitution in the viral VPg protein was responsible for the appearance of symptoms, whereas one substitution in the viral P3 protein the epistatically contributed to exacerbate severity. DNA microarray analyses show that the evolved and ancestral viruses affect the global patterns of host gene expression in radically different ways. A major difference is that genes involved in stress and pathogen response are not activated upon infection with the evolved virus, suggesting that selection has favored viral strategies to escape from host defenses.",2008 Jun 11,"['Agudelo-Romero, Patricia', 'Carbonell, Pablo', 'Perez-Amador, Miguel A.', 'Elena, Santiago F.']",PLoS One,,,True
566bdd537595b38dc6ab764b13d6d9ae33f9c9af,PMC,Mouse Hepatitis Coronavirus RNA Replication Depends on GBF1-Mediated ARF1 Activation,http://dx.doi.org/10.1371/journal.ppat.1000088,PMC2398782,18551169,CC BY,"Coronaviruses induce in infected cells the formation of double membrane vesicles, which are the sites of RNA replication. Not much is known about the formation of these vesicles, although recent observations indicate an important role for the endoplasmic reticulum in the formation of the mouse hepatitis coronavirus (MHV) replication complexes (RCs). We now show that MHV replication is sensitive to brefeldin A (BFA). Consistently, expression of a dominant-negative mutant of ARF1, known to mimic the action of the drug, inhibited MHV infection profoundly. Immunofluorescence analysis and quantitative electron microscopy demonstrated that BFA did not block the formation of RCs per se, but rather reduced their number. MHV RNA replication was not sensitive to BFA in MDCK cells, which are known to express the BFA-resistant guanine nucleotide exchange factor GBF1. Accordingly, individual knockdown of the Golgi-resident targets of BFA by transfection of small interfering RNAs (siRNAs) showed that GBF1, but not BIG1 or BIG2, was critically involved in MHV RNA replication. ARF1, the cellular effector of GBF1, also appeared to be involved in MHV replication, as siRNAs targeting this small GTPase inhibited MHV infection significantly. Collectively, our results demonstrate that GBF1-mediated ARF1 activation is required for efficient MHV RNA replication and reveal that the early secretory pathway and MHV replication complex formation are closely connected.",2008 Jun 13,"['Verheije, Monique H.', 'Raaben, Matthijs', 'Mari, Muriel', 'te Lintelo, Eddie G.', 'Reggiori, Fulvio', 'van Kuppeveld, Frank J. M.', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.']",PLoS Pathog,,,True
0132b8c2721692d9f53bd33a738fa94618bb4e91,PMC,Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays,http://dx.doi.org/10.1186/1471-2180-8-76,PMC2408589,18482458,CC BY,"BACKGROUND: Syphilis spirochete Treponema pallidum ssp. pallidum remains the enigmatic pathogen, since no virulence factors have been identified and the pathogenesis of the disease is poorly understood. Increasing rates of new syphilis cases per year have been observed recently. RESULTS: The genome of the SS14 strain was sequenced to high accuracy by an oligonucleotide array strategy requiring hybridization to only three arrays (Comparative Genome Sequencing, CGS). Gaps in the resulting sequence were filled with targeted dideoxy-terminators (DDT) sequencing and the sequence was confirmed by whole genome fingerprinting (WGF). When compared to the Nichols strain, 327 single nucleotide substitutions (224 transitions, 103 transversions), 14 deletions, and 18 insertions were found. On the proteome level, the highest frequency of amino acid-altering substitution polymorphisms was in novel genes, while the lowest was in housekeeping genes, as expected by their evolutionary conservation. Evidence was also found for hypervariable regions and multiple regions showing intrastrain heterogeneity in the T. pallidum chromosome. CONCLUSION: The observed genetic changes do not have influence on the ability of Treponema pallidum to cause syphilitic infection, since both SS14 and Nichols are virulent in rabbit. However, this is the first assessment of the degree of variation between the two syphilis pathogens and paves the way for phylogenetic studies of this fascinating organism.",2008 May 15,"['Matějková, Petra', 'Strouhal, Michal', 'Šmajs, David', 'Norris, Steven J', 'Palzkill, Timothy', 'Petrosino, Joseph F', 'Sodergren, Erica', 'Norton, Jason E', 'Singh, Jaz', 'Richmond, Todd A', 'Molla, Michael N', 'Albert, Thomas J', 'Weinstock, George M']",BMC Microbiol,,,True
0db939582f9ab5bb71581348ca000231d901c2f8,PMC,Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays,http://dx.doi.org/10.1186/1471-2180-8-76,PMC2408589,18482458,CC BY,"BACKGROUND: Syphilis spirochete Treponema pallidum ssp. pallidum remains the enigmatic pathogen, since no virulence factors have been identified and the pathogenesis of the disease is poorly understood. Increasing rates of new syphilis cases per year have been observed recently. RESULTS: The genome of the SS14 strain was sequenced to high accuracy by an oligonucleotide array strategy requiring hybridization to only three arrays (Comparative Genome Sequencing, CGS). Gaps in the resulting sequence were filled with targeted dideoxy-terminators (DDT) sequencing and the sequence was confirmed by whole genome fingerprinting (WGF). When compared to the Nichols strain, 327 single nucleotide substitutions (224 transitions, 103 transversions), 14 deletions, and 18 insertions were found. On the proteome level, the highest frequency of amino acid-altering substitution polymorphisms was in novel genes, while the lowest was in housekeeping genes, as expected by their evolutionary conservation. Evidence was also found for hypervariable regions and multiple regions showing intrastrain heterogeneity in the T. pallidum chromosome. CONCLUSION: The observed genetic changes do not have influence on the ability of Treponema pallidum to cause syphilitic infection, since both SS14 and Nichols are virulent in rabbit. However, this is the first assessment of the degree of variation between the two syphilis pathogens and paves the way for phylogenetic studies of this fascinating organism.",2008 May 15,"['Matějková, Petra', 'Strouhal, Michal', 'Šmajs, David', 'Norris, Steven J', 'Palzkill, Timothy', 'Petrosino, Joseph F', 'Sodergren, Erica', 'Norton, Jason E', 'Singh, Jaz', 'Richmond, Todd A', 'Molla, Michael N', 'Albert, Thomas J', 'Weinstock, George M']",BMC Microbiol,,,False
84a964d5dde5ffc12076b7c43ac5fff52210ad61,PMC,Comparative analysis of full genomic sequences among different genotypes of dengue virus type 3,http://dx.doi.org/10.1186/1743-422X-5-63,PMC2413216,18495043,CC BY,"BACKGROUND: Although the previous study demonstrated the envelope protein of dengue viruses is under purifying selection pressure, little is known about the genetic differences of full-length viral genomes of DENV-3. In our study, complete genomic sequencing of DENV-3 strains collected from different geographical locations and isolation years were determined and the sequence diversity as well as selection pressure sites in the DENV genome other than within the E gene were also analyzed. RESULTS: Using maximum likelihood and Bayesian approaches, our phylogenetic analysis revealed that the Taiwan's indigenous DENV-3 isolated from 1994 and 1998 dengue/DHF epidemics and one 1999 sporadic case were of the three different genotypes – I, II, and III, each associated with DENV-3 circulating in Indonesia, Thailand and Sri Lanka, respectively. Sequence diversity and selection pressure of different genomic regions among DENV-3 different genotypes was further examined to understand the global DENV-3 evolution. The highest nucleotide sequence diversity among the fully sequenced DENV-3 strains was found in the nonstructural protein 2A (mean ± SD: 5.84 ± 0.54) and envelope protein gene regions (mean ± SD: 5.04 ± 0.32). Further analysis found that positive selection pressure of DENV-3 may occur in the non-structural protein 1 gene region and the positive selection site was detected at position 178 of the NS1 gene. CONCLUSION: Our study confirmed that the envelope protein is under purifying selection pressure although it presented higher sequence diversity. The detection of positive selection pressure in the non-structural protein along genotype II indicated that DENV-3 originated from Southeast Asia needs to monitor the emergence of DENV strains with epidemic potential for better epidemic prevention and vaccine development.",2008 May 21,"['King, Chwan-Chuen', 'Chao, Day-Yu', 'Chien, Li-Jung', 'Chang, Gwong-Jen J', 'Lin, Ting-Hsiang', 'Wu, Yin-Chang', 'Huang, Jyh-Hsiung']",Virol J,,,True
86680d2981c3e641e014e777c8769031b89f933e,PMC,Healthcare workers' attitudes towards working during pandemic influenza: A multi method study,http://dx.doi.org/10.1186/1471-2458-8-192,PMC2423372,18518971,CC BY,"BACKGROUND: Healthcare workers (HCWs) will be key players in any response to pandemic influenza, and will be in the front line of exposure to infection. Responding effectively to a pandemic relies on the majority of medical, nursing, laboratory and hotel services staff continuing to work normally. Planning assumes that during a pandemic normal healthcare service levels will be provided, although it anticipates that as caseloads increase only essential care will be provided. The ability of the NHS to provide expected service levels is entirely dependent upon HCWs continuing to work as normal. METHODS/DESIGN: This study is designed as a two-phase multi-method study, incorporating focus groups and a questionnaire survey. In phase one, qualitative methods will be used to collect the views of a purposive sample of HCWs, to determine the range of factors associated with their responses to the prospect of working through pandemic influenza. In phase two, the findings from the focus groups, combined with the available literature, will be used to inform the design of a survey to determine the generalisability of these factors, enabling the estimation of the likely proportion of HCWs affected by each factor, and how likely it is that they would be willing and/or able to continue to work during an influenza pandemic. DISCUSSION: There are potentially greater than normal health risks for some healthcare workers working during a pandemic, and these workers may be concerned about infecting family members/friends. HCWs will be as liable as other workers to care for sick family members and friends. It is vital to have information about how motivated HCWs will be to continue to work during such a crisis, and what factors might influence their decision to work/not to work. Through the identification and subsequent management of these factors it may be possible to implement strategies that will alleviate the concerns and fears of HCWs and remove potential barriers to working.",2008 Jun 2,"['Draper, Heather', 'Wilson, Sue', 'Ives, Jonathan', 'Gratus, Christine', 'Greenfield, Sheila', 'Parry, Jayne', 'Petts, Judith', 'Sorell, Tom']",BMC Public Health,,,True
4873db67f7f48325e1c63ccfa093d5077a9c9b50,PMC,HyperISGylation of Old World Monkey ISG15 in Human Cells,http://dx.doi.org/10.1371/journal.pone.0002427,PMC2423471,18560560,CC BY,"BACKGROUND: ISG15 is an Ubiquitin-like protein, highly induced by Type I Interferons. Upon the cooperative activity of specific Ubiquitinating enzymes, ISG15 can be conjugated to its substrates. Increasing evidence points to a role for protein ISGylation in anti-viral and anti-tumoral defense. PRINCIPAL FINDINGS: We identified ISG15 from Old World Monkeys (OWm) as a hyper-efficient protein modifier. Western blot analysis visualized more efficient conjugation of OWmISG15 relative to HuISG15 in human (Hu), monkey and mouse (Mo) cell-lines. Moreover, the substrates of OWmISG15 identified upon Tandem Affinity Purification followed by LC-MS/MS identification largely outnumbered these of HuISG15 itself. Several Ubiquitin-Conjugating enzymes were identified as novel ISGylated substrates. Introduction of a N89D mutation in HuISG15 improved its ISGylation capacity, and additional Q31K/T33A/D133N mutations yielded a HuISG15 variant with an ISGylation efficiency comparable to OWmISG15. Homology modeling and structural superposition situate N89 in the interaction interface with the Activating enzyme. Analysis of the UbE1L residues in this interface revealed a striking homology between OWmUbE1L and HuUbE1, the Activating enzyme of Ubiquitin. In line with this observation, we found efficient activation of AgmISG15, but not HuISG15 or MoISG15, by HuUbE1, thus providing a likely explanation for OWm hyperISGylation. CONCLUSIONS: This study discloses the poor conjugation competence of HuISG15 compared to OWmISG15 and maps the critical determinants for efficient conjugation. HyperISGylation may greatly assist ISGylation studies and may enhance its function as positive regulator of Interferon-related immune responses or as anti-tumoral modulator.",2008 Jun 18,"['Pattyn, Els', 'Verhee, Annick', 'Uyttendaele, Isabel', 'Piessevaux, Julie', 'Timmerman, Evy', 'Gevaert, Kris', 'Vandekerckhove, Joël', 'Peelman, Frank', 'Tavernier, Jan']",PLoS One,,,True
976496c92ea74a516df11ebb445433f724e7f522,PMC,Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters,http://dx.doi.org/10.1186/1743-422X-5-69,PMC2426676,18519001,CC BY,"BACKGROUND: Human metapneumovirus (hMPV) infection can cause acute lower respiratory tract illness in infants, the immunocompromised, and the elderly. Currently there are no licensed preventative measures for hMPV infections. Using a variant of hMPV/NL/1/00 that does not require trypsin supplementation for growth in tissue culture, we deleted the M2-2 gene and evaluated the replication of rhMPV/ΔM2-2 virus in vitro and in vivo. RESULTS: In vitro studies showed that the ablation of M2-2 increased the propensity for insertion of U nucleotides in poly-U tracts of the genomic RNA. In addition, viral transcription was up-regulated although the level of genomic RNA remained comparable to rhMPV. Thus, deletion of M2-2 alters the ratio between hMPV genome copies and transcripts. In vivo, rhMPV/ΔM2-2 was attenuated compared to rhMPV in the lungs and nasal turbinates of hamsters. Hamsters immunized with one dose of rhMPV/ΔM2-2 were protected from challenge with 10(6 )PFU of wild type (wt) hMPV/NL/1/00. CONCLUSION: Our results suggest that hMPV M2-2 alters regulation of transcription and influences the fidelity of the polymerase complex during viral genome replication. In the hamster model, rhMPVΔM2-2 is attenuated and protective suggesting that deletion of M2-2 may result in a potential live vaccine candidate. A more thorough knowledge of the hMPV polymerase complex and the role of M2-2 during hMPV replication are being studied as we develop a potential live hMPV vaccine candidate that lacks M2-2 expression.",2008 Jun 3,"['Schickli, Jeanne H', 'Kaur, Jasmine', 'MacPhail, Mia', 'Guzzetta, Jeanne M', 'Spaete, Richard R', 'Tang, Roderick S']",Virol J,,,True
9e45efb86c7c552be221e4d1356d9374a7ebc204,PMC,Ubiquitination Is Required for Effective Replication of Coxsackievirus B3,http://dx.doi.org/10.1371/journal.pone.0002585,PMC2440516,18612413,CC BY,"BACKGROUND: Protein ubiquitination and/or degradation by the ubiquitin/proteasome system (UPS) have been recognized as critical mechanisms in the regulation of numerous essential cellular functions. The importance of the UPS in viral pathogenesis has become increasingly apparent. Using murine cardiomyocytes, we have previously demonstrated that the UPS plays a key role in the replication of coxsackievirus B3 (CVB3), an important human pathogen associated with various diseases. To further elucidate the underlying mechanisms, we examined the interplay between the UPS and CVB3, focusing on the role of ubiquitination in viral lifecycle. METHODOLOGY/PRINCIPAL FINDINGS: As assessed by in situ hybridization, Western blot, and plaque assay, we showed that proteasome inhibition decreased CVB3 RNA replication, protein synthesis, and viral titers in HeLa cells. There were no apparent changes in 20S proteasome activities following CVB3 infection. However, we found viral infection led to an accumulation of protein-ubiquitin conjugates, accompanied by a decreased protein expression of free ubiquitin, implicating an important role of ubiquitination in the UPS-mediated viral replication. Using small-interfering RNA, we demonstrated that gene-silencing of ubiquitin significantly reduced viral titers, possibly through downregulation of protein ubiquitination and subsequent alteration of protein function and/or degradation. Inhibition of deubiquitinating enzymes apparently enhances the inhibitory effects of proteasome inhibitors on CVB3 replication. Finally, by immunoprecipitation, we showed that coxsackieviral polymerase 3D was post-translationally modified by ubiquitination and such modification might be a prerequisite for its function in transcriptional regulation of viral genome. CONCLUSION: Coxsackievirus infection promotes protein ubiquitination, contributing to effective viral replication, probably through ubiquitin modification of viral polymerase.",2008 Jul 9,"['Si, Xiaoning', 'Gao, Guang', 'Wong, Jerry', 'Wang, Yahong', 'Zhang, Jingchun', 'Luo, Honglin']",PLoS One,,,True
6bfd7a2e092c039e792bae569c8406f2a47c2759,PMC,Professional and Home-Made Face Masks Reduce Exposure to Respiratory Infections among the General Population,http://dx.doi.org/10.1371/journal.pone.0002618,PMC2440799,18612429,CC BY,"BACKGROUND: Governments are preparing for a potential influenza pandemic. Therefore they need data to assess the possible impact of interventions. Face-masks worn by the general population could be an accessible and affordable intervention, if effective when worn under routine circumstances. METHODOLOGY: We assessed transmission reduction potential provided by personal respirators, surgical masks and home-made masks when worn during a variety of activities by healthy volunteers and a simulated patient. PRINCIPAL FINDINGS: All types of masks reduced aerosol exposure, relatively stable over time, unaffected by duration of wear or type of activity, but with a high degree of individual variation. Personal respirators were more efficient than surgical masks, which were more efficient than home-made masks. Regardless of mask type, children were less well protected. Outward protection (mask wearing by a mechanical head) was less effective than inward protection (mask wearing by healthy volunteers). CONCLUSIONS/SIGNIFICANCE: Any type of general mask use is likely to decrease viral exposure and infection risk on a population level, in spite of imperfect fit and imperfect adherence, personal respirators providing most protection. Masks worn by patients may not offer as great a degree of protection against aerosol transmission.",2008 Jul 9,"['van der Sande, Marianne', 'Teunis, Peter', 'Sabel, Rob']",PLoS One,,,True
0cd96fd42139b22b63e5752eda2c38990a18763a,PMC,Oct-4 Expression Maintained Cancer Stem-Like Properties in Lung Cancer-Derived CD133-Positive Cells,http://dx.doi.org/10.1371/journal.pone.0002637,PMC2440807,18612434,CC BY,"CD133 (prominin-1), a 5-transmembrane glycoprotein, has recently been considered to be an important marker that represents the subset population of cancer stem-like cells. Herein we report the isolation of CD133-positive cells (LC-CD133(+)) and CD133-negative cells (LC-CD133(−)) from tissue samples of ten patients with non-small cell lung cancer (LC) and five LC cell lines. LC-CD133(+) displayed higher Oct-4 expressions with the ability to self-renew and may represent a reservoir with proliferative potential for generating lung cancer cells. Furthermore, LC-CD133(+), unlike LC-CD133(−), highly co-expressed the multiple drug-resistant marker ABCG2 and showed significant resistance to chemotherapy agents (i.e., cisplatin, etoposide, doxorubicin, and paclitaxel) and radiotherapy. The treatment of Oct-4 siRNA with lentiviral vector can specifically block the capability of LC-CD133(+) to form spheres and can further facilitate LC-CD133(+) to differentiate into LC-CD133(−). In addition, knock-down of Oct-4 expression in LC-CD133(+) can significantly inhibit the abilities of tumor invasion and colony formation, and increase apoptotic activities of caspase 3 and poly (ADP-ribose) polymerase (PARP). Finally, in vitro and in vivo studies further confirm that the treatment effect of chemoradiotherapy for LC-CD133(+) can be improved by the treatment of Oct-4 siRNA. In conclusion, we demonstrated that Oct-4 expression plays a crucial role in maintaining the self-renewing, cancer stem-like, and chemoradioresistant properties of LC-CD133(+). Future research is warranted regarding the up-regulated expression of Oct-4 in LC-CD133(+) and malignant lung cancer.",2008 Jul 9,"['Chen, Yu-Chih', 'Hsu, Han-Shui', 'Chen, Yi-Wei', 'Tsai, Tung-Hu', 'How, Chorng-Kuang', 'Wang, Chien-Ying', 'Hung, Shih-Chieh', 'Chang, Yuh-Lih', 'Tsai, Ming-Long', 'Lee, Yi-Yen', 'Ku, Hung-Hai', 'Chiou, Shih-Hwa']",PLoS One,,,True
505d4036449010b44702841ae2564d6a55a3fbcd,PMC,Virus-Like Particles of SARS-Like Coronavirus Formed by Membrane Proteins from Different Origins Demonstrate Stimulating Activity in Human Dendritic Cells,http://dx.doi.org/10.1371/journal.pone.0002685,PMC2441860,18628832,CC BY,"The pathogenesis of SARS coronavirus (CoV) remains poorly understood. In the current study, two recombinant baculovirus were generated to express the spike (S) protein of SARS-like coronavirus (SL-CoV) isolated from bats (vAcBS) and the envelope (E) and membrane (M) proteins of SARS-CoV, respectively. Co-infection of insect cells with these two recombinant baculoviruses led to self-assembly of virus-like particles (BVLPs) as demonstrated by electron microscopy. Incorporation of S protein of vAcBS (BS) into VLPs was confirmed by western blot and immunogold labeling. Such BVLPs up-regulated the level of CD40, CD80, CD86, CD83, and enhanced the secretion of IL-6, IL-10 and TNF-α in immature dendritic cells (DCs). Immune responses were compared in immature DCs inoculated with BVLPs or with VLPs formed by S, E and M proteins of human SARS-CoV. BVLPs showed a stronger ability to stimulate DCs in terms of cytokine induction as evidenced by 2 to 6 fold higher production of IL-6 and TNF-α. Further study indicated that IFN-γ+ and IL-4+ populations in CD4+ T cells increased upon co-cultivation with DCs pre-exposed with BVLPs or SARS-CoV VLPs. The observed difference in DC-stimulating activity between BVLPs and SARS CoV VLPs was very likely due to the S protein. In agreement, SL-CoV S DNA vaccine evoked a more vigorous antibody response and a stronger T cell response than SARS-CoV S DNA in mice. Our data have demonstrated for the first time that SL-CoV VLPs formed by membrane proteins of different origins, one from SL-CoV isolated from bats (BS) and the other two from human SARS-CoV (E and M), activated immature DCs and enhanced the expression of co-stimulatory molecules and the secretion of cytokines. Finding in this study may provide important information for vaccine development as well as for understanding the pathogenesis of SARS-like CoV.",2008 Jul 16,"['Bai, Bingke', 'Hu, Qinxue', 'Hu, Hui', 'Zhou, Peng', 'Shi, Zhengli', 'Meng, Jin', 'Lu, Baojing', 'Huang, Yi', 'Mao, Panyong', 'Wang, Hanzhong']",PLoS One,,,True
1b7c700ee3a33c0a675a5f7e71a20ce62467b900,PMC,Expression of HIV-1 antigens in plants as potential subunit vaccines,http://dx.doi.org/10.1186/1472-6750-8-53,PMC2443125,18573204,CC BY,"BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) has infected more than 40 million people worldwide, mainly in sub-Saharan Africa. The high prevalence of HIV-1 subtype C in southern Africa necessitates the development of cheap, effective vaccines. One means of production is the use of plants, for which a number of different techniques have been successfully developed. HIV-1 Pr55Gag is a promising HIV-1 vaccine candidate: we compared the expression of this and a truncated Gag (p17/p24) and the p24 capsid subunit in Nicotiana spp. using transgenic plants and transient expression via Agrobacterium tumefaciens and recombinant tobamovirus vectors. We also investigated the influence of subcellular localisation of recombinant protein to the chloroplast and the endoplasmic reticulum (ER) on protein yield. We partially purified a selected vaccine candidate and tested its stimulation of a humoral and cellular immune response in mice. RESULTS: Both transient and transgenic expression of the HIV antigens were successful, although expression of Pr55Gag was low in all systems; however, the Agrobacterium-mediated transient expression of p24 and p17/p24 yielded best, to more than 1 mg p24/kg fresh weight. Chloroplast targeted protein levels were highest in transient and transgenic expression of p24 and p17/p24. The transiently-expressed p17/p24 was not immunogenic in mice as a homologous vaccine, but it significantly boosted a humoral and T cell immune response primed by a gag DNA vaccine, pTHGagC. CONCLUSION: Transient agroinfiltration was best for expression of all of the recombinant proteins tested, and p24 and p17/p24 were expressed at much higher levels than Pr55Gag. Our results highlight the usefulness of plastid signal peptides in enhancing the production of recombinant proteins meant for use as vaccines. The p17/p24 protein effectively boosted T cell and humoral responses in mice primed by the DNA vaccine pTHGagC, showing that this plant-produced protein has potential for use as a vaccine.",2008 Jun 23,"['Meyers, Ann', 'Chakauya, Ereck', 'Shephard, Enid', 'Tanzer, Fiona L', 'Maclean, James', 'Lynch, Alisson', 'Williamson, Anna-Lise', 'Rybicki, Edward P']",BMC Biotechnol,,,True
77138f50684f6b8c48752afd24cbb63abaad4aa4,PMC,"Gatekeepers of health: A qualitative assessment of child care centre staff's perspectives, practices and challenges to enteric illness prevention and management in child care centres",http://dx.doi.org/10.1186/1471-2458-8-212,PMC2443801,18554408,CC BY,"BACKGROUND: Enteric outbreaks associated with child care centres (CCC) have been well documented internationally and in Canada. The current literature focuses on identifying potential risk factors for introduction and transmission of enteric disease, but does not examine why these risk factors happen, how the risk is understood and managed by the staff of CCCs, or what challenges they experience responding to enteric illness. The purpose of this study was to explore the understanding, knowledge and actions of CCC staff regarding enteric illness and outbreaks, and to identify challenges that staff encounter while managing them. METHODS: Focus groups were conducted with staff of regulated CCCs in Southern Ontario. Five focus groups were held with 40 participants. An open ended style of interviewing was used. Data were analyzed using content analysis. RESULTS: CCC staff play an important role in preventing and managing enteric illness. Staff used in-depth knowledge of the children, the centre and their personal experiences to assist in making decisions related to enteric illness. The decisions and actions may differ from guidance provided by public health officials, particularly when faced with challenges related to time, money, staffing and parents. CONCLUSION: CCC staff relied on experience and judgment in coordination with public health information to assist decision-making in the management of enteric illness and outbreaks. Advice and guidance from public health officials to CCC staff needs to be consistent yet flexible so that it may be adapted in a variety of situations and meet regulatory and public health requirements.",2008 Jun 13,"['Taylor, Marsha', 'Adams, Cindy L', 'Ellis, Andrea']",BMC Public Health,,,True
341a9a57e865081e81a9c60b97802773761ce8c4,PMC,Dating the time of viral subtype divergence,http://dx.doi.org/10.1186/1471-2148-8-172,PMC2443812,18541033,CC BY,"Precise dating of viral subtype divergence enables researchers to correlate divergence with geographic and demographic occurrences. When historical data are absent (that is, the overwhelming majority), viral sequence sampling on a time scale commensurate with the rate of substitution permits the inference of the times of subtype divergence. Currently, researchers use two strategies to approach this task, both requiring strong conditions on the molecular clock assumption of substitution rate. As the underlying structure of the substitution rate process at the time of subtype divergence is not understood and likely highly variable, we present a simple method that estimates rates of substitution, and from there, times of divergence, without use of an assumed molecular clock. We accomplish this by blending estimates of the substitution rate for triplets of dated sequences where each sequence draws from a distinct viral subtype, providing a zeroth-order approximation for the rate between subtypes. As an example, we calculate the time of divergence for three genes among influenza subtypes A-H3N2 and B using subtype C as an outgroup. We show a time of divergence approximately 100 years ago, substantially more recent than previous estimates which range from 250 to 3800 years ago.",2008 Jun 9,"[""O'Brien, John D"", 'She, Zhen-Su', 'Suchard, Marc A']",BMC Evol Biol,,,True
d73eaecdf6e03c65d962791c98563c8a7d5cf79a,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.60,PMC2447222,,CC BY,,2001 Dec,,Comp Funct Genomics,,,True
17d0d25ab7105e239f9d13e41489d01d9a40c34a,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.231,PMC2447311,,CC BY,,2003 Dec,,Comp Funct Genomics,,,True
692bdad285cb5d0d0f00e949bb323fc13cc56750,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.350,PMC2447323,,CC BY,,2004 Feb,,Comp Funct Genomics,,,False
d9f0fd49a89212c8d2089c84cd9a9d8573277288,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.355,PMC2447430,,CC BY,,2004 Aug-Oct,,Comp Funct Genomics,,,True
f670f4bb6f79e54d7603f8520853b1f0d105b588,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.353,PMC2447453,,CC BY,,2004 Jun,,Comp Funct Genomics,,,True
bc403b497ddc13f1a5352d7eef9d0fdaeccbc028,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.357,PMC2447475,,CC BY,,2004 Dec,,Comp Funct Genomics,,,True
cfacb72c36e1bb7fade469d8bf5ebc12143e0b3e,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.421,PMC2447482,,CC BY,,2005 Jun,,Comp Funct Genomics,,,True
e8b3d7f86dd48b422693465d39ce72280df5527c,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.425,PMC2447491,,CC BY,,2005 Oct-Dec,,Comp Funct Genomics,,,True
cef34a0d6cfce0c84ac90fb01338bb2429693d9e,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.422,PMC2447508,,CC BY,,2005 Jul-Aug,,Comp Funct Genomics,,,True
2eb279d1dfd4b3649ed0ff00c4e5a72261d445a0,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.419,PMC2448604,,CC BY,,2005 Feb-Mar,,Comp Funct Genomics,,,True
023dff96542ca1e77e3a1d08a2f3893ca1ebc057,PMC,"Sequences, Annotation and Single Nucleotide Polymorphism of the Major Histocompatibility Complex in the Domestic Cat",http://dx.doi.org/10.1371/journal.pone.0002674,PMC2453318,18629345,CC0,"Two sequences of major histocompatibility complex (MHC) regions in the domestic cat, 2.976 and 0.362 Mbps, which were separated by an ancient chromosome break (55–80 MYA) and followed by a chromosomal inversion were annotated in detail. Gene annotation of this MHC was completed and identified 183 possible coding regions, 147 human homologues, possible functional genes and 36 pseudo/unidentified genes) by GENSCAN and BLASTN, BLASTP RepeatMasker programs. The first region spans 2.976 Mbp sequence, which encodes six classical class II antigens (three DRA and three DRB antigens) lacking the functional DP, DQ regions, nine antigen processing molecules (DOA/DOB, DMA/DMB, TAPASIN, and LMP2/LMP7,TAP1/TAP2), 52 class III genes, nineteen class I genes/gene fragments (FLAI-A to FLAI-S). Three class I genes (FLAI-H, I-K, I-E) may encode functional classical class I antigens based on deduced amino acid sequence and promoter structure. The second region spans 0.362 Mbp sequence encoding no class I genes and 18 cross-species conserved genes, excluding class I, II and their functionally related/associated genes, namely framework genes, including three olfactory receptor genes. One previously identified feline endogenous retrovirus, a baboon retrovirus derived sequence (ECE1) and two new endogenous retrovirus sequences, similar to brown bat endogenous retrovirus (FERVmlu1, FERVmlu2) were found within a 140 Kbp interval in the middle of class I region. MHC SNPs were examined based on comparisons of this BAC sequence and MHC homozygous 1.9× WGS sequences and found that 11,654 SNPs in 2.84 Mbp (0.00411 SNP per bp), which is 2.4 times higher rate than average heterozygous region in the WGS (0.0017 SNP per bp genome), and slightly higher than the SNP rate observed in human MHC (0.00337 SNP per bp).",2008 Jul 16,"['Yuhki, Naoya', 'Mullikin, James C.', 'Beck, Thomas', 'Stephens, Robert', ""O'Brien, Stephen J.""]",PLoS One,,,True
103c89c60d7d24bb8432c4b7a61379f9e44fe6ea,PMC,Does Pathogen Spillover from Commercially Reared Bumble Bees Threaten Wild Pollinators?,http://dx.doi.org/10.1371/journal.pone.0002771,PMC2464710,18648661,CC BY,"The conservation of insect pollinators is drawing attention because of reported declines in bee species and the ‘ecosystem services’ they provide. This issue has been brought to a head by recent devastating losses of honey bees throughout North America (so called, ‘Colony Collapse Disorder’); yet, we still have little understanding of the cause(s) of bee declines. Wild bumble bees (Bombus spp.) have also suffered serious declines and circumstantial evidence suggests that pathogen ‘spillover’ from commercially reared bumble bees, which are used extensively to pollinate greenhouse crops, is a possible cause. We constructed a spatially explicit model of pathogen spillover in bumble bees and, using laboratory experiments and the literature, estimated parameter values for the spillover of Crithidia bombi, a destructive pathogen commonly found in commercial Bombus. We also monitored wild bumble bee populations near greenhouses for evidence of pathogen spillover, and compared the fit of our model to patterns of C. bombi infection observed in the field. Our model predicts that, during the first three months of spillover, transmission from commercial hives would infect up to 20% of wild bumble bees within 2 km of the greenhouse. However, a travelling wave of disease is predicted to form suddenly, infecting up to 35–100% of wild Bombus, and spread away from the greenhouse at a rate of 2 km/wk. In the field, although we did not observe a large epizootic wave of infection, the prevalences of C. bombi near greenhouses were consistent with our model. Indeed, we found that spillover has allowed C. bombi to invade several wild bumble bee species near greenhouses. Given the available evidence, it is likely that pathogen spillover from commercial bees is contributing to the ongoing decline of wild Bombus in North America. Improved management of domestic bees, for example by reducing their parasite loads and their overlap with wild congeners, could diminish or even eliminate pathogen spillover.",2008 Jul 23,"['Otterstatter, Michael C.', 'Thomson, James D.']",PLoS One,,,True
78b008cc190700f5c0291d67cca3112f6b54aa1f,PMC,Temporal trends in the discovery of human viruses,http://dx.doi.org/10.1098/rspb.2008.0294,PMC2475551,18505720,CC BY,"On average, more than two new species of human virus are reported every year. We constructed the cumulative species discovery curve for human viruses going back to 1901. We fitted a statistical model to these data; the shape of the curve strongly suggests that the process of virus discovery is far from complete. We generated a 95% credible interval for the pool of as yet undiscovered virus species of 38–562. We extrapolated the curve and generated an estimate of 10–40 new species to be discovered by 2020. Although we cannot predict the level of health threat that these new viruses will present, we conclude that novel virus species must be anticipated in public health planning. More systematic virus discovery programmes, covering both humans and potential animal reservoirs of human viruses, should be considered.",2008 Sep 22,"['Woolhouse, Mark E.J', 'Howey, Richard', 'Gaunt, Eleanor', 'Reilly, Liam', 'Chase-Topping, Margo', 'Savill, Nick']",Proc Biol Sci,,,True
72f9a628e9d59676c5cbed4485e64c5757a4c78a,PMC,Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997–2006),http://dx.doi.org/10.1371/journal.pone.0002768,PMC2481298,18648550,CC BY,"BACKGROUND: The underlying basis for the seasonality of influenza A viruses is still uncertain. Phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: 281 complete hemagglutinin (HA) and neuraminidase (NA) sequences were obtained from influenza A(H3N2) viruses, collected over 10 years (1997–2006) from Hong Kong. These dated sequences were analyzed with influenza A(H3N2) vaccine strain sequences (Syd/5/97, Mos/10/99, Fuj/411/02, Cal/7/04) and 315 other publicly available dated sequences from elsewhere, worldwide. In addition, the NA sequence alignment was inspected for the presence of any naturally occurring, known, neuraminidase inhibitor (NAI) resistance-associated amino acid mutations (R292K and E119V). Before 2001, the Hong Kong HA and NA sequences clustered more closely with the older vaccine sequences (Syd/5/97, Mos/10/99) than did sequences from elsewhere. After 2001, this trend reversed with significant clusters containing HA and NA sequences from different locations, isolated at different times, suggesting that viral migration may account for much of the influenza A(H3N2) seasonality during this 10-year period. However, at least one example from Hong Kong was found suggesting that in some years, influenza A(H3N2) viruses may persist in the same location, perhaps continuing to circulate, sub-clinically, at low levels between seasons, to re-emerge in the influenza season the following year, relatively unchanged. None of these Hong Kong influenza A(H3N2) NA sequences contained any of the known NAI-resistance associated mutations. CONCLUSIONS/SIGNIFICANCE: The seasonality of influenza A(H3N2) may be largely due to global migration, with similar viruses appearing in different countries at different times. However, occasionally, some viruses may remain within a single location and continue to circulate within that population, to re-emerge during the next influenza season, with relatively little genetic change. Naturally occurring NAI resistance mutations were absent or, at least, very rare in this population.",2008 Jul 23,"['Tang, Julian W.', 'Ngai, Karry L. K.', 'Lam, Wai Y.', 'Chan, Paul K. S.']",PLoS One,,,True
6cd550c5672e5101c0047c22993ec1466e3ac185,PMC,Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997–2006),http://dx.doi.org/10.1371/journal.pone.0002768,PMC2481298,18648550,CC BY,"BACKGROUND: The underlying basis for the seasonality of influenza A viruses is still uncertain. Phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: 281 complete hemagglutinin (HA) and neuraminidase (NA) sequences were obtained from influenza A(H3N2) viruses, collected over 10 years (1997–2006) from Hong Kong. These dated sequences were analyzed with influenza A(H3N2) vaccine strain sequences (Syd/5/97, Mos/10/99, Fuj/411/02, Cal/7/04) and 315 other publicly available dated sequences from elsewhere, worldwide. In addition, the NA sequence alignment was inspected for the presence of any naturally occurring, known, neuraminidase inhibitor (NAI) resistance-associated amino acid mutations (R292K and E119V). Before 2001, the Hong Kong HA and NA sequences clustered more closely with the older vaccine sequences (Syd/5/97, Mos/10/99) than did sequences from elsewhere. After 2001, this trend reversed with significant clusters containing HA and NA sequences from different locations, isolated at different times, suggesting that viral migration may account for much of the influenza A(H3N2) seasonality during this 10-year period. However, at least one example from Hong Kong was found suggesting that in some years, influenza A(H3N2) viruses may persist in the same location, perhaps continuing to circulate, sub-clinically, at low levels between seasons, to re-emerge in the influenza season the following year, relatively unchanged. None of these Hong Kong influenza A(H3N2) NA sequences contained any of the known NAI-resistance associated mutations. CONCLUSIONS/SIGNIFICANCE: The seasonality of influenza A(H3N2) may be largely due to global migration, with similar viruses appearing in different countries at different times. However, occasionally, some viruses may remain within a single location and continue to circulate within that population, to re-emerge during the next influenza season, with relatively little genetic change. Naturally occurring NAI resistance mutations were absent or, at least, very rare in this population.",2008 Jul 23,"['Tang, Julian W.', 'Ngai, Karry L. K.', 'Lam, Wai Y.', 'Chan, Paul K. S.']",PLoS One,,,False
d1d195d19219b396b2cf7dcaf3e3911aa3d6c516,PMC,Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997–2006),http://dx.doi.org/10.1371/journal.pone.0002768,PMC2481298,18648550,CC BY,"BACKGROUND: The underlying basis for the seasonality of influenza A viruses is still uncertain. Phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: 281 complete hemagglutinin (HA) and neuraminidase (NA) sequences were obtained from influenza A(H3N2) viruses, collected over 10 years (1997–2006) from Hong Kong. These dated sequences were analyzed with influenza A(H3N2) vaccine strain sequences (Syd/5/97, Mos/10/99, Fuj/411/02, Cal/7/04) and 315 other publicly available dated sequences from elsewhere, worldwide. In addition, the NA sequence alignment was inspected for the presence of any naturally occurring, known, neuraminidase inhibitor (NAI) resistance-associated amino acid mutations (R292K and E119V). Before 2001, the Hong Kong HA and NA sequences clustered more closely with the older vaccine sequences (Syd/5/97, Mos/10/99) than did sequences from elsewhere. After 2001, this trend reversed with significant clusters containing HA and NA sequences from different locations, isolated at different times, suggesting that viral migration may account for much of the influenza A(H3N2) seasonality during this 10-year period. However, at least one example from Hong Kong was found suggesting that in some years, influenza A(H3N2) viruses may persist in the same location, perhaps continuing to circulate, sub-clinically, at low levels between seasons, to re-emerge in the influenza season the following year, relatively unchanged. None of these Hong Kong influenza A(H3N2) NA sequences contained any of the known NAI-resistance associated mutations. CONCLUSIONS/SIGNIFICANCE: The seasonality of influenza A(H3N2) may be largely due to global migration, with similar viruses appearing in different countries at different times. However, occasionally, some viruses may remain within a single location and continue to circulate within that population, to re-emerge during the next influenza season, with relatively little genetic change. Naturally occurring NAI resistance mutations were absent or, at least, very rare in this population.",2008 Jul 23,"['Tang, Julian W.', 'Ngai, Karry L. K.', 'Lam, Wai Y.', 'Chan, Paul K. S.']",PLoS One,,,False
8467a3df4f6a9a8e33efd8134bc13394c70c6740,PMC,Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997–2006),http://dx.doi.org/10.1371/journal.pone.0002768,PMC2481298,18648550,CC BY,"BACKGROUND: The underlying basis for the seasonality of influenza A viruses is still uncertain. Phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: 281 complete hemagglutinin (HA) and neuraminidase (NA) sequences were obtained from influenza A(H3N2) viruses, collected over 10 years (1997–2006) from Hong Kong. These dated sequences were analyzed with influenza A(H3N2) vaccine strain sequences (Syd/5/97, Mos/10/99, Fuj/411/02, Cal/7/04) and 315 other publicly available dated sequences from elsewhere, worldwide. In addition, the NA sequence alignment was inspected for the presence of any naturally occurring, known, neuraminidase inhibitor (NAI) resistance-associated amino acid mutations (R292K and E119V). Before 2001, the Hong Kong HA and NA sequences clustered more closely with the older vaccine sequences (Syd/5/97, Mos/10/99) than did sequences from elsewhere. After 2001, this trend reversed with significant clusters containing HA and NA sequences from different locations, isolated at different times, suggesting that viral migration may account for much of the influenza A(H3N2) seasonality during this 10-year period. However, at least one example from Hong Kong was found suggesting that in some years, influenza A(H3N2) viruses may persist in the same location, perhaps continuing to circulate, sub-clinically, at low levels between seasons, to re-emerge in the influenza season the following year, relatively unchanged. None of these Hong Kong influenza A(H3N2) NA sequences contained any of the known NAI-resistance associated mutations. CONCLUSIONS/SIGNIFICANCE: The seasonality of influenza A(H3N2) may be largely due to global migration, with similar viruses appearing in different countries at different times. However, occasionally, some viruses may remain within a single location and continue to circulate within that population, to re-emerge during the next influenza season, with relatively little genetic change. Naturally occurring NAI resistance mutations were absent or, at least, very rare in this population.",2008 Jul 23,"['Tang, Julian W.', 'Ngai, Karry L. K.', 'Lam, Wai Y.', 'Chan, Paul K. S.']",PLoS One,,,False
596e771e860af036be53a0f54e56d815348c329c,PMC,Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997–2006),http://dx.doi.org/10.1371/journal.pone.0002768,PMC2481298,18648550,CC BY,"BACKGROUND: The underlying basis for the seasonality of influenza A viruses is still uncertain. Phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: 281 complete hemagglutinin (HA) and neuraminidase (NA) sequences were obtained from influenza A(H3N2) viruses, collected over 10 years (1997–2006) from Hong Kong. These dated sequences were analyzed with influenza A(H3N2) vaccine strain sequences (Syd/5/97, Mos/10/99, Fuj/411/02, Cal/7/04) and 315 other publicly available dated sequences from elsewhere, worldwide. In addition, the NA sequence alignment was inspected for the presence of any naturally occurring, known, neuraminidase inhibitor (NAI) resistance-associated amino acid mutations (R292K and E119V). Before 2001, the Hong Kong HA and NA sequences clustered more closely with the older vaccine sequences (Syd/5/97, Mos/10/99) than did sequences from elsewhere. After 2001, this trend reversed with significant clusters containing HA and NA sequences from different locations, isolated at different times, suggesting that viral migration may account for much of the influenza A(H3N2) seasonality during this 10-year period. However, at least one example from Hong Kong was found suggesting that in some years, influenza A(H3N2) viruses may persist in the same location, perhaps continuing to circulate, sub-clinically, at low levels between seasons, to re-emerge in the influenza season the following year, relatively unchanged. None of these Hong Kong influenza A(H3N2) NA sequences contained any of the known NAI-resistance associated mutations. CONCLUSIONS/SIGNIFICANCE: The seasonality of influenza A(H3N2) may be largely due to global migration, with similar viruses appearing in different countries at different times. However, occasionally, some viruses may remain within a single location and continue to circulate within that population, to re-emerge during the next influenza season, with relatively little genetic change. Naturally occurring NAI resistance mutations were absent or, at least, very rare in this population.",2008 Jul 23,"['Tang, Julian W.', 'Ngai, Karry L. K.', 'Lam, Wai Y.', 'Chan, Paul K. S.']",PLoS One,,,False
1e2989b7156dc944d0a24b596fd17aaa08b3b56c,PMC,A phase 1 trial of nebulised heparin in acute lung injury,http://dx.doi.org/10.1186/cc6894,PMC2481447,18460218,CC BY,"INTRODUCTION: Animal studies of acute lung injury (ALI) suggest nebulised heparin may limit damage from fibrin deposition in the alveolar space and microcirculation. No human studies have been undertaken to date. We assessed the feasibility, safety and potential anticoagulant effects of administration of nebulised heparin to patients with ALI. METHODS: An open label phase 1 trial of four escalating doses of nebulised heparin was performed. A total of 16 ventilated patients with ALI were studied. The first group was administered a total of 50,000 U/day, the second group 100,000 U/day, the third group 200,000 U/day and the fourth group 400,000 U/day. Assessments of lung function included the PaO(2)/FiO(2 )ratio, lung compliance and the alveolar dead space fraction. Monitoring of anticoagulation included the activated partial thromboplastin time (APTT) and the thrombin clotting time. Bronchoalveolar lavage fluid was collected and the prothrombin fragment and tissue plasminogen activator levels were assessed. Analysis of variance was used to compare the effects of dose. RESULTS: No serious adverse events occurred for any dose. The changes over time for the PaO(2)/FiO(2 )ratio, lung compliance and the alveolar dead space fraction levels were similar for all doses. A trend to increased APTT and thrombin clotting time levels was present with higher doses (P = 0.09 and P = 0.1, respectively). For the highest dose, the APTT reached 64 seconds; following cessation of nebulised heparin, the APTT fell to 39 seconds (P = 0.06). In bronchoalveolar lavage samples a trend to reduced prothrombin fragment levels was present with higher doses (P = 0.1), while tissue plasminogen activator levels were similar for all doses. CONCLUSION: Administration of nebulised heparin to mechanically ventilated patients with ALI is feasible. Nebulised heparin was not associated with any serious adverse events, and at higher doses it increased APTT levels. Larger trials are required to further investigate the safety and efficacy of nebulised heparin. In these trials due consideration must be given to systemic anticoagulant effects. TRIAL REGISTRATION: Australian Clinical trials registry ACTRN12606000388516.",2008 May 6,"['Dixon, Barry', 'Santamaria, John D', 'Campbell, Duncan J']",Crit Care,,,True
6ed1c5f102cce4bbcbd9d5438b6b8be3d4746484,PMC,H5N1 and 1918 Pandemic Influenza Virus Infection Results in Early and Excessive Infiltration of Macrophages and Neutrophils in the Lungs of Mice,http://dx.doi.org/10.1371/journal.ppat.1000115,PMC2483250,18670648,CC0,"Fatal human respiratory disease associated with the 1918 pandemic influenza virus and potentially pandemic H5N1 viruses is characterized by severe lung pathology, including pulmonary edema and extensive inflammatory infiltrate. Here, we quantified the cellular immune response to infection in the mouse lung by flow cytometry and demonstrate that mice infected with highly pathogenic (HP) H1N1 and H5N1 influenza viruses exhibit significantly high numbers of macrophages and neutrophils in the lungs compared to mice infected with low pathogenic (LP) viruses. Mice infected with the 1918 pandemic virus and a recent H5N1 human isolate show considerable similarities in overall lung cellularity, lung immune cell sub-population composition and cellular immune temporal dynamics. Interestingly, while these similarities were observed, the HP H5N1 virus consistently elicited significantly higher levels of pro-inflammatory cytokines in whole lungs and primary human macrophages, revealing a potentially critical difference in the pathogenesis of H5N1 infections. These results together show that infection with HP influenza viruses such as H5N1 and the 1918 pandemic virus leads to a rapid cell recruitment of macrophages and neutrophils into the lungs, suggesting that these cells play a role in acute lung inflammation associated with HP influenza virus infection. In addition, primary macrophages and dendritic cells were also susceptible to 1918 and H5N1 influenza virus infection in vitro and in infected mouse lung tissue.",2008 Aug 1,"['Perrone, Lucy A.', 'Plowden, Julie K.', 'García-Sastre, Adolfo', 'Katz, Jacqueline M.', 'Tumpey, Terrence M.']",PLoS Pathog,,,True
17b8edaf62be1b907bf750a94c4b881f3db1f7be,PMC,Gene silencing by RNAi in mouse Sertoli cells,http://dx.doi.org/10.1186/1477-7827-6-29,PMC2483279,18620581,CC BY,"BACKGROUND: RNA interference (RNAi) is a valuable tool in the investigation of gene function. The purpose of this study was to examine the availability, target cell types and efficiency of RNAi in the mouse seminiferous epithelium. METHODS: The experimental model was based on transgenic mice expressing EGFP (enhanced green fluorescent protein). RNAi was induced by in vivo transfection of plasmid vectors encoding for short hairpin RNAs (shRNAs) targeting EGFP. shRNAs were transfected in vivo by microinjection into the seminiferous tubules via the rete testis followed by square wave electroporation. As a transfection reporter, expression of red fluorescent protein (HcRed 1) was used. Cell types, the efficiency of both transfections and RNAi were all evaluated. RESULTS: Sertoli cells were the main transfected cells. A reduction of about 40% in the level of EGFP protein was detected in cells successfully transfected both in vivo and in vitro. However, the efficiency of in vivo transfection was low. CONCLUSION: In adult seminiferous epithelial cells, in vivo post-transcriptional gene silencing mediated by RNAi via shRNA is efficient in Sertoli cells. Similar levels of RNAi were detected both in vivo and in vitro. This also indicates that Sertoli cells have the necessary silencing machinery to repress the expression of endogenous genes via RNAi.",2008 Jul 11,"['González-González, Emilio', 'López-Casas, Pedro P', 'del Mazo, Jesús']",Reprod Biol Endocrinol,,,True
01c6c44650ad5466cdb134a28d0b14700fa3906d,PMC,Patterns of Positive Selection in Six Mammalian Genomes,http://dx.doi.org/10.1371/journal.pgen.1000144,PMC2483296,18670650,CC BY,"Genome-wide scans for positively selected genes (PSGs) in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes. However, previous scans have been limited in power and accuracy owing to small numbers of available genomes. Here we present the most comprehensive examination of mammalian PSGs to date, using the six high-coverage genome assemblies now available for eutherian mammals. The increased phylogenetic depth of this dataset results in substantially improved statistical power, and permits several new lineage- and clade-specific tests to be applied. Of ∼16,500 human genes with high-confidence orthologs in at least two other species, 400 genes showed significant evidence of positive selection (FDR<0.05), according to a standard likelihood ratio test. An additional 144 genes showed evidence of positive selection on particular lineages or clades. As in previous studies, the identified PSGs were enriched for roles in defense/immunity, chemosensory perception, and reproduction, but enrichments were also evident for more specific functions, such as complement-mediated immunity and taste perception. Several pathways were strongly enriched for PSGs, suggesting possible co-evolution of interacting genes. A novel Bayesian analysis of the possible “selection histories” of each gene indicated that most PSGs have switched multiple times between positive selection and nonselection, suggesting that positive selection is often episodic. A detailed analysis of Affymetrix exon array data indicated that PSGs are expressed at significantly lower levels, and in a more tissue-specific manner, than non-PSGs. Genes that are specifically expressed in the spleen, testes, liver, and breast are significantly enriched for PSGs, but no evidence was found for an enrichment for PSGs among brain-specific genes. This study provides additional evidence for widespread positive selection in mammalian evolution and new genome-wide insights into the functional implications of positive selection.",2008 Aug 1,"['Kosiol, Carolin', 'Vinař, Tomáš', 'da Fonseca, Rute R.', 'Hubisz, Melissa J.', 'Bustamante, Carlos D.', 'Nielsen, Rasmus', 'Siepel, Adam']",PLoS Genet,,,True
ac7dab707a31d84f05dbc9136dba4cf3770183dd,PMC,Patterns of Positive Selection in Six Mammalian Genomes,http://dx.doi.org/10.1371/journal.pgen.1000144,PMC2483296,18670650,CC BY,"Genome-wide scans for positively selected genes (PSGs) in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes. However, previous scans have been limited in power and accuracy owing to small numbers of available genomes. Here we present the most comprehensive examination of mammalian PSGs to date, using the six high-coverage genome assemblies now available for eutherian mammals. The increased phylogenetic depth of this dataset results in substantially improved statistical power, and permits several new lineage- and clade-specific tests to be applied. Of ∼16,500 human genes with high-confidence orthologs in at least two other species, 400 genes showed significant evidence of positive selection (FDR<0.05), according to a standard likelihood ratio test. An additional 144 genes showed evidence of positive selection on particular lineages or clades. As in previous studies, the identified PSGs were enriched for roles in defense/immunity, chemosensory perception, and reproduction, but enrichments were also evident for more specific functions, such as complement-mediated immunity and taste perception. Several pathways were strongly enriched for PSGs, suggesting possible co-evolution of interacting genes. A novel Bayesian analysis of the possible “selection histories” of each gene indicated that most PSGs have switched multiple times between positive selection and nonselection, suggesting that positive selection is often episodic. A detailed analysis of Affymetrix exon array data indicated that PSGs are expressed at significantly lower levels, and in a more tissue-specific manner, than non-PSGs. Genes that are specifically expressed in the spleen, testes, liver, and breast are significantly enriched for PSGs, but no evidence was found for an enrichment for PSGs among brain-specific genes. This study provides additional evidence for widespread positive selection in mammalian evolution and new genome-wide insights into the functional implications of positive selection.",2008 Aug 1,"['Kosiol, Carolin', 'Vinař, Tomáš', 'da Fonseca, Rute R.', 'Hubisz, Melissa J.', 'Bustamante, Carlos D.', 'Nielsen, Rasmus', 'Siepel, Adam']",PLoS Genet,,,False
63e7c7d005ecaf98cbd7daa6bdbe66998c4c4322,PMC,Patterns of Positive Selection in Six Mammalian Genomes,http://dx.doi.org/10.1371/journal.pgen.1000144,PMC2483296,18670650,CC BY,"Genome-wide scans for positively selected genes (PSGs) in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes. However, previous scans have been limited in power and accuracy owing to small numbers of available genomes. Here we present the most comprehensive examination of mammalian PSGs to date, using the six high-coverage genome assemblies now available for eutherian mammals. The increased phylogenetic depth of this dataset results in substantially improved statistical power, and permits several new lineage- and clade-specific tests to be applied. Of ∼16,500 human genes with high-confidence orthologs in at least two other species, 400 genes showed significant evidence of positive selection (FDR<0.05), according to a standard likelihood ratio test. An additional 144 genes showed evidence of positive selection on particular lineages or clades. As in previous studies, the identified PSGs were enriched for roles in defense/immunity, chemosensory perception, and reproduction, but enrichments were also evident for more specific functions, such as complement-mediated immunity and taste perception. Several pathways were strongly enriched for PSGs, suggesting possible co-evolution of interacting genes. A novel Bayesian analysis of the possible “selection histories” of each gene indicated that most PSGs have switched multiple times between positive selection and nonselection, suggesting that positive selection is often episodic. A detailed analysis of Affymetrix exon array data indicated that PSGs are expressed at significantly lower levels, and in a more tissue-specific manner, than non-PSGs. Genes that are specifically expressed in the spleen, testes, liver, and breast are significantly enriched for PSGs, but no evidence was found for an enrichment for PSGs among brain-specific genes. This study provides additional evidence for widespread positive selection in mammalian evolution and new genome-wide insights into the functional implications of positive selection.",2008 Aug 1,"['Kosiol, Carolin', 'Vinař, Tomáš', 'da Fonseca, Rute R.', 'Hubisz, Melissa J.', 'Bustamante, Carlos D.', 'Nielsen, Rasmus', 'Siepel, Adam']",PLoS Genet,,,False
9bc181d540a6368fb97eaa7cf4e0f852c22e7826,PMC,Patterns of Positive Selection in Six Mammalian Genomes,http://dx.doi.org/10.1371/journal.pgen.1000144,PMC2483296,18670650,CC BY,"Genome-wide scans for positively selected genes (PSGs) in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes. However, previous scans have been limited in power and accuracy owing to small numbers of available genomes. Here we present the most comprehensive examination of mammalian PSGs to date, using the six high-coverage genome assemblies now available for eutherian mammals. The increased phylogenetic depth of this dataset results in substantially improved statistical power, and permits several new lineage- and clade-specific tests to be applied. Of ∼16,500 human genes with high-confidence orthologs in at least two other species, 400 genes showed significant evidence of positive selection (FDR<0.05), according to a standard likelihood ratio test. An additional 144 genes showed evidence of positive selection on particular lineages or clades. As in previous studies, the identified PSGs were enriched for roles in defense/immunity, chemosensory perception, and reproduction, but enrichments were also evident for more specific functions, such as complement-mediated immunity and taste perception. Several pathways were strongly enriched for PSGs, suggesting possible co-evolution of interacting genes. A novel Bayesian analysis of the possible “selection histories” of each gene indicated that most PSGs have switched multiple times between positive selection and nonselection, suggesting that positive selection is often episodic. A detailed analysis of Affymetrix exon array data indicated that PSGs are expressed at significantly lower levels, and in a more tissue-specific manner, than non-PSGs. Genes that are specifically expressed in the spleen, testes, liver, and breast are significantly enriched for PSGs, but no evidence was found for an enrichment for PSGs among brain-specific genes. This study provides additional evidence for widespread positive selection in mammalian evolution and new genome-wide insights into the functional implications of positive selection.",2008 Aug 1,"['Kosiol, Carolin', 'Vinař, Tomáš', 'da Fonseca, Rute R.', 'Hubisz, Melissa J.', 'Bustamante, Carlos D.', 'Nielsen, Rasmus', 'Siepel, Adam']",PLoS Genet,,,False
c86eba5cb05531b033922afbe3f9148d1cd3c5dc,PMC,Patterns of Positive Selection in Six Mammalian Genomes,http://dx.doi.org/10.1371/journal.pgen.1000144,PMC2483296,18670650,CC BY,"Genome-wide scans for positively selected genes (PSGs) in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes. However, previous scans have been limited in power and accuracy owing to small numbers of available genomes. Here we present the most comprehensive examination of mammalian PSGs to date, using the six high-coverage genome assemblies now available for eutherian mammals. The increased phylogenetic depth of this dataset results in substantially improved statistical power, and permits several new lineage- and clade-specific tests to be applied. Of ∼16,500 human genes with high-confidence orthologs in at least two other species, 400 genes showed significant evidence of positive selection (FDR<0.05), according to a standard likelihood ratio test. An additional 144 genes showed evidence of positive selection on particular lineages or clades. As in previous studies, the identified PSGs were enriched for roles in defense/immunity, chemosensory perception, and reproduction, but enrichments were also evident for more specific functions, such as complement-mediated immunity and taste perception. Several pathways were strongly enriched for PSGs, suggesting possible co-evolution of interacting genes. A novel Bayesian analysis of the possible “selection histories” of each gene indicated that most PSGs have switched multiple times between positive selection and nonselection, suggesting that positive selection is often episodic. A detailed analysis of Affymetrix exon array data indicated that PSGs are expressed at significantly lower levels, and in a more tissue-specific manner, than non-PSGs. Genes that are specifically expressed in the spleen, testes, liver, and breast are significantly enriched for PSGs, but no evidence was found for an enrichment for PSGs among brain-specific genes. This study provides additional evidence for widespread positive selection in mammalian evolution and new genome-wide insights into the functional implications of positive selection.",2008 Aug 1,"['Kosiol, Carolin', 'Vinař, Tomáš', 'da Fonseca, Rute R.', 'Hubisz, Melissa J.', 'Bustamante, Carlos D.', 'Nielsen, Rasmus', 'Siepel, Adam']",PLoS Genet,,,True
9d08aa9bb599cb599ceaa62f31cb480a5708a5d1,PMC,Delayed Treatment of Diagnosed Pulmonary Tuberculosis in Taiwan,http://dx.doi.org/10.1186/1471-2458-8-236,PMC2483710,18620595,CC BY,"BACKGROUND: Mycobacterium tuberculosis infection is an ongoing public health problem in Taiwan. The National Tuberculosis Registry Campaign, a case management system, was implemented in 1997. This study examined this monitoring system to identify and characterize delayed treatment of TB patients. METHODS: Records of all tuberculosis cases treated in Taiwan from 2002 through 2005 were obtained from the National Tuberculosis Registry Campaign. Initiation of treatment more than 7 days after diagnosis was considered a long treatment delay. RESULTS: The study included 31,937 patients. The mean day of delayed treatment was 3.6 days. Most patients were treated immediately after diagnosis. The relationship between number of TB patients and days of delayed treatment after diagnosis exhibited a Power-law distribution. The long tail of the power-law distribution indicated that an extreme number occur cannot be neglected. Tuberculosis patients treated after an unusually long delay require close observation and follow up. CONCLUSION: This study found that TB control is generally acceptabl in Taiwan; however, delayed treatment increases the risk of transmission. Improving the protocol for managing confirmed TB cases can minimize disease transmission.",2008 Jul 13,"['Chern, Jimmy PS', 'Chen, Duan-Rung', 'Wen, Tzai-Hung']",BMC Public Health,,,True
3fbbb5c2047570f4c33a88cb927a6f54e83de658,PMC,Mathematical Analysis of Copy Number Variation in a DNA Sample Using Digital PCR on a Nanofluidic Device,http://dx.doi.org/10.1371/journal.pone.0002876,PMC2483940,18682853,CC BY,"Copy Number Variations (CNVs) of regions of the human genome have been associated with multiple diseases. We present an algorithm which is mathematically sound and computationally efficient to accurately analyze CNV in a DNA sample utilizing a nanofluidic device, known as the digital array. This numerical algorithm is utilized to compute copy number variation and the associated statistical confidence interval and is based on results from probability theory and statistics. We also provide formulas which can be used as close approximations.",2008 Aug 6,"['Dube, Simant', 'Qin, Jian', 'Ramakrishnan, Ramesh']",PLoS One,,,True
176274e5fb44083ebc8c91d87e013d624533c7f6,PMC,Conservation and Variability of Dengue Virus Proteins: Implications for Vaccine Design,http://dx.doi.org/10.1371/journal.pntd.0000272,PMC2491585,18698358,CC BY,"BACKGROUND: Genetic variation and rapid evolution are hallmarks of RNA viruses, the result of high mutation rates in RNA replication and selection of mutants that enhance viral adaptation, including the escape from host immune responses. Variability is uneven across the genome because mutations resulting in a deleterious effect on viral fitness are restricted. RNA viruses are thus marked by protein sites permissive to multiple mutations and sites critical to viral structure-function that are evolutionarily robust and highly conserved. Identification and characterization of the historical dynamics of the conserved sites have relevance to multiple applications, including potential targets for diagnosis, and prophylactic and therapeutic purposes. METHODOLOGY/PRINCIPAL FINDINGS: We describe a large-scale identification and analysis of evolutionarily highly conserved amino acid sequences of the entire dengue virus (DENV) proteome, with a focus on sequences of 9 amino acids or more, and thus immune-relevant as potential T-cell determinants. DENV protein sequence data were collected from the NCBI Entrez protein database in 2005 (9,512 sequences) and again in 2007 (12,404 sequences). Forty-four (44) sequences (pan-DENV sequences), mainly those of nonstructural proteins and representing ∼15% of the DENV polyprotein length, were identical in 80% or more of all recorded DENV sequences. Of these 44 sequences, 34 (∼77%) were present in ≥95% of sequences of each DENV type, and 27 (∼61%) were conserved in other Flaviviruses. The frequencies of variants of the pan-DENV sequences were low (0 to ∼5%), as compared to variant frequencies of ∼60 to ∼85% in the non pan-DENV sequence regions. We further showed that the majority of the conserved sequences were immunologically relevant: 34 contained numerous predicted human leukocyte antigen (HLA) supertype-restricted peptide sequences, and 26 contained T-cell determinants identified by studies with HLA-transgenic mice and/or reported to be immunogenic in humans. CONCLUSIONS/SIGNIFICANCE: Forty-four (44) pan-DENV sequences of at least 9 amino acids were highly conserved and identical in 80% or more of all recorded DENV sequences, and the majority were found to be immune-relevant by their correspondence to known or putative HLA-restricted T-cell determinants. The conservation of these sequences through the entire recorded DENV genetic history supports their possible value for diagnosis, prophylactic and/or therapeutic applications. The combination of bioinformatics and experimental approaches applied herein provides a framework for large-scale and systematic analysis of conserved and variable sequences of other pathogens, in particular, for rapidly mutating viruses, such as influenza A virus and HIV.",2008 Aug 13,"['Khan, Asif M.', 'Miotto, Olivo', 'Nascimento, Eduardo J. M.', 'Srinivasan, K. N.', 'Heiny, A. T.', 'Zhang, Guang Lan', 'Marques, E. T.', 'Tan, Tin Wee', 'Brusic, Vladimir', 'Salmon, Jerome', 'August, J. Thomas']",PLoS Negl Trop Dis,,,True
d3738503734864a3cb54929b145611300ebcd4de,PMC,Conservation and Variability of Dengue Virus Proteins: Implications for Vaccine Design,http://dx.doi.org/10.1371/journal.pntd.0000272,PMC2491585,18698358,CC BY,"BACKGROUND: Genetic variation and rapid evolution are hallmarks of RNA viruses, the result of high mutation rates in RNA replication and selection of mutants that enhance viral adaptation, including the escape from host immune responses. Variability is uneven across the genome because mutations resulting in a deleterious effect on viral fitness are restricted. RNA viruses are thus marked by protein sites permissive to multiple mutations and sites critical to viral structure-function that are evolutionarily robust and highly conserved. Identification and characterization of the historical dynamics of the conserved sites have relevance to multiple applications, including potential targets for diagnosis, and prophylactic and therapeutic purposes. METHODOLOGY/PRINCIPAL FINDINGS: We describe a large-scale identification and analysis of evolutionarily highly conserved amino acid sequences of the entire dengue virus (DENV) proteome, with a focus on sequences of 9 amino acids or more, and thus immune-relevant as potential T-cell determinants. DENV protein sequence data were collected from the NCBI Entrez protein database in 2005 (9,512 sequences) and again in 2007 (12,404 sequences). Forty-four (44) sequences (pan-DENV sequences), mainly those of nonstructural proteins and representing ∼15% of the DENV polyprotein length, were identical in 80% or more of all recorded DENV sequences. Of these 44 sequences, 34 (∼77%) were present in ≥95% of sequences of each DENV type, and 27 (∼61%) were conserved in other Flaviviruses. The frequencies of variants of the pan-DENV sequences were low (0 to ∼5%), as compared to variant frequencies of ∼60 to ∼85% in the non pan-DENV sequence regions. We further showed that the majority of the conserved sequences were immunologically relevant: 34 contained numerous predicted human leukocyte antigen (HLA) supertype-restricted peptide sequences, and 26 contained T-cell determinants identified by studies with HLA-transgenic mice and/or reported to be immunogenic in humans. CONCLUSIONS/SIGNIFICANCE: Forty-four (44) pan-DENV sequences of at least 9 amino acids were highly conserved and identical in 80% or more of all recorded DENV sequences, and the majority were found to be immune-relevant by their correspondence to known or putative HLA-restricted T-cell determinants. The conservation of these sequences through the entire recorded DENV genetic history supports their possible value for diagnosis, prophylactic and/or therapeutic applications. The combination of bioinformatics and experimental approaches applied herein provides a framework for large-scale and systematic analysis of conserved and variable sequences of other pathogens, in particular, for rapidly mutating viruses, such as influenza A virus and HIV.",2008 Aug 13,"['Khan, Asif M.', 'Miotto, Olivo', 'Nascimento, Eduardo J. M.', 'Srinivasan, K. N.', 'Heiny, A. T.', 'Zhang, Guang Lan', 'Marques, E. T.', 'Tan, Tin Wee', 'Brusic, Vladimir', 'Salmon, Jerome', 'August, J. Thomas']",PLoS Negl Trop Dis,,,False
26a931d514eb3f80a779ec6d06997e1d77278dd4,PMC,"Topology of evolving, mutagenized viral populations: quasispecies expansion, compression, and operation of negative selection",http://dx.doi.org/10.1186/1471-2148-8-207,PMC2515104,18637173,CC BY,"BACKGROUND: The molecular events and evolutionary forces underlying lethal mutagenesis of virus (or virus extinction through an excess of mutations) are not well understood. Here we apply for the first time phylogenetic methods and Partition Analysis of Quasispecies (PAQ) to monitor genetic distances and intra-population structures of mutant spectra of foot-and-mouth disease virus (FMDV) quasispecies subjected to mutagenesis by base and nucleoside analogues. RESULTS: Phylogenetic and PAQ analyses have revealed a highly dynamic variation of intrapopulation diversity of FMDV quasispecies. The population diversity first suffers striking expansions in the presence of mutagens and then compressions either when the presence of the mutagenic analogue was discontinued or when a mutation that decreased sensitivity to a mutagen was selected. The pattern of mutations found in the populations was in agreement with the behavior of the corresponding nucleotide analogues with FMDV in vitro. Mutations accumulated at preferred genomic sites, and dn/ds ratios indicate the operation of negative (or purifying) selection in populations subjected to mutagenesis. No evidence of unusually elevated genetic distances has been obtained for FMDV populations approaching extinction. CONCLUSION: Phylogenetic and PAQ analysis provide adequate procedures to describe the evolution of viral sequences subjected to lethal mutagenesis. These methods define the changes of intra-population structure more precisely than mutation frequencies and Shannon entropies. PAQ is very sensitive to variations of intrapopulation genetic distances. Strong negative (or purifying) selection operates in FMDV populations subjected to enhanced mutagenesis. The quantifications provide evidence that extinction does not imply unusual increases of intrapopulation complexity, in support of the lethal defection model of virus extinction.",2008 Jul 17,"['Ojosnegros, Samuel', 'Agudo, Rubén', 'Sierra, Macarena', 'Briones, Carlos', 'Sierra, Saleta', 'González- López, Claudia', 'Domingo, Esteban', 'Cristina, Juan']",BMC Evol Biol,,,True
1d45a0c89997d27fe2e01fbee4b407e01cc595c4,PMC,Evolutionary and Transmission Dynamics of Reassortant H5N1 Influenza Virus in Indonesia,http://dx.doi.org/10.1371/journal.ppat.1000130,PMC2515348,18725937,CC BY,"H5N1 highly pathogenic avian influenza (HPAI) viruses have seriously affected the Asian poultry industry since their recurrence in 2003. The viruses pose a threat of emergence of a global pandemic influenza through point mutation or reassortment leading to a strain that can effectively transmit among humans. In this study, we present phylogenetic evidences for the interlineage reassortment among H5N1 HPAI viruses isolated from humans, cats, and birds in Indonesia, and identify the potential genetic parents of the reassorted genome segments. Parsimony analyses of viral phylogeography suggest that the reassortant viruses may have originated from greater Jakarta and surroundings, and subsequently spread to other regions in the West Java province. In addition, Bayesian methods were used to elucidate the genetic diversity dynamics of the reassortant strain and one of its genetic parents, which revealed a more rapid initial growth of genetic diversity in the reassortant viruses relative to their genetic parent. These results demonstrate that interlineage exchange of genetic information may play a pivotal role in determining viral genetic diversity in a focal population. Moreover, our study also revealed significantly stronger diversifying selection on the M1 and PB2 genes in the lineages preceding and subsequent to the emergence of the reassortant viruses, respectively. We discuss how the corresponding mutations might drive the adaptation and onward transmission of the newly formed reassortant viruses.",2008 Aug 22,"['Lam, Tommy Tsan-Yuk', 'Hon, Chung-Chau', 'Pybus, Oliver G.', 'Kosakovsky Pond, Sergei L.', 'Wong, Raymond Tze-Yeung', 'Yip, Chi-Wai', 'Zeng, Fanya', 'Leung, Frederick Chi-Ching']",PLoS Pathog,,,True
402fd2b6ffd34c3d1fb4aca45d84bd7079284d99,PMC,Sampling for Global Epidemic Models and the Topology of an International Airport Network,http://dx.doi.org/10.1371/journal.pone.0003154,PMC2522280,18776932,CC BY,"Mathematical models that describe the global spread of infectious diseases such as influenza, severe acute respiratory syndrome (SARS), and tuberculosis (TB) often consider a sample of international airports as a network supporting disease spread. However, there is no consensus on how many cities should be selected or on how to select those cities. Using airport flight data that commercial airlines reported to the Official Airline Guide (OAG) in 2000, we have examined the network characteristics of network samples obtained under different selection rules. In addition, we have examined different size samples based on largest flight volume and largest metropolitan populations. We have shown that although the bias in network characteristics increases with the reduction of the sample size, a relatively small number of areas that includes the largest airports, the largest cities, the most-connected cities, and the most central cities is enough to describe the dynamics of the global spread of influenza. The analysis suggests that a relatively small number of cities (around 200 or 300 out of almost 3000) can capture enough network information to adequately describe the global spread of a disease such as influenza. Weak traffic flows between small airports can contribute to noise and mask other means of spread such as the ground transportation.",2008 Sep 8,"['Bobashev, Georgiy', 'Morris, Robert J.', 'Goedecke, D. Michael']",PLoS One,,,True
ba4cb142734825c7a8f759f10edfbc58ff798f9c,PMC,Life threatening pneumonia in a lupus patient: a case report,http://dx.doi.org/10.1186/1757-1626-1-70,PMC2526065,18671866,CC BY,"We report a case of systemic lupus erythematosus (SLE) in a 44-year old Caucasian woman complicated with pneumonia and severe respiratory failure requiring ICU treatment and mechanical ventilation. Symptoms developed in a generally well controlled SLE course after sudden stop in immunosupresant therapy (methotrexate, cyclosporin and methylprednisolone). A fulminant course of the disease, an interstitial pattern in a high resolution computed tomography (HRCT) and negative repeated sputum, blood and bronchoaspirate cultures enabled diagnosis of fulminant lupus pneumonitis. The response to pulses of cyclophosphamide and methylprednisolone was good but complicated with a significant leukopenia. HRCT confirmed significant remission of pulmonary changes. Fulminant lupus pneumonitis is a rare but potentially life threatening complication of SLE. Differential diagnosis requires exclusion of pneumonia induced by pathogens such as Pneumocystis jirovevecii (carinii) and Mycobacterium sp. Intensive immunosuppressive therapy and close cooperation between ICU, pulmonology and rheumatology departments is necessary in such a case to minimalize the risk of fatal outcome.",2008 Jul 31,"['Kupczyk, Maciej', 'Antczak, Adam', 'Kuna, Piotr', 'Górski, Paweł']",Cases J,,,True
c851a889568efd469f724ebacfe3270946f3e04f,PMC,Endothelial Cells Support Persistent Gammaherpesvirus 68 Infection,http://dx.doi.org/10.1371/journal.ppat.1000152,PMC2526176,18787698,CC BY,"A variety of human diseases are associated with gammaherpesviruses, including neoplasms of lymphocytes (e.g. Burkitt's lymphoma) and endothelial cells (e.g. Kaposi's sarcoma). Gammaherpesvirus infections usually result in either a productive lytic infection, characterized by expression of all viral genes and rapid cell lysis, or latent infection, characterized by limited viral gene expression and no cell lysis. Here, we report characterization of endothelial cell infection with murine gammaherpesvirus 68 (γHV68), a virus phylogenetically related and biologically similar to the human gammaherpesviruses. Endothelial cells supported γHV68 replication in vitro, but were unique in that a significant proportion of the cells escaped lysis, proliferated, and remained viable in culture for an extended time. Upon infection, endothelial cells became non-adherent and altered in size, complexity, and cell-surface protein expression. These cells were uniformly infected and expressed the lytic transcription program based on detection of abundant viral gene transcripts, GFP fluorescence from the viral genome, and viral surface protein expression. Additionally, endothelial cells continued to produce new infectious virions as late as 30 days post-infection. The outcome of this long-term infection was promoted by the γHV68 v-cyclin, because in the absence of the v-cyclin, viability was significantly reduced following infection. Importantly, infected primary endothelial cells also demonstrated increased viability relative to infected primary fibroblasts, and this increased viability was dependent on the v-cyclin. Finally, we provide evidence for infection of endothelial cells in vivo in immune-deficient mice. The extended viability and virus production of infected endothelial cells indicated that endothelial cells provided a source of prolonged virus production and identify a cell-type specific adaptation of gammaherpesvirus replication. While infected endothelial cells would likely be cleared in a healthy individual, persistently infected endothelial cells could provide a source of continued virus replication in immune-compromised individuals, a context in which gammaherpesvirus-associated pathology frequently occurs.",2008 Sep 12,"['Suárez, Andrea Luísa', 'van Dyk, Linda Faye']",PLoS Pathog,,,True
35808155b612d2189d338168dc1cc0e0b7401661,PMC,Selection of reference genes for qRT-PCR examination of wild populations of Atlantic cod Gadus morhua,http://dx.doi.org/10.1186/1756-0500-1-47,PMC2527504,18710500,CC BY,"BACKGROUND: Extensive sequencing efforts have been taking place for the Atlantic cod (Gadus morhua) in recent years, the number of ESTs in the Genbank has reached more than 140.000. Despite its importance in North Atlantic fisheries and potential use in aquaculture, relatively few gene expression examination exists for this species, and systematic evaluations of reference gene stability in quantitative real-time RT-PCR (qRT-PCR) studies are lacking. RESULTS: The stability of 10 potential reference genes was examined in six tissues of Atlantic cod obtained from four populations, to determine the most suitable genes to be used in qRT-PCR analyses. Relative transcription levels of genes encoding β-actin (ACTB), elongation factor 1A (EF1A), actin-related protein-2 (ARP-2), glyceraldehyde-3P-dehydrogenase (GAPDH), ubiquitin (Ubi), acidic ribosomal protein (ARP), ribosomal protein S9 (S9), ribosomal protein L4 (RPL4), RPL22 and RPL37 were quantified in gills, brain, liver, head kidney, muscle and middle intestine in six juvenile fish from three wild populations and from farmed Atlantic cod. Reference gene stability was investigated using the geNorm and NormFinder tools. Based on calculations performed with the geNorm, which determines the most stable genes from a set of tested genes in a given cDNA sample, ARP, Ubi, S9 and RPL37 were among the most stable genes in all tissues. When the same calculations were done with NormFinder, the same genes plus RPL4 and EF1A were ranked as the preferable genes. CONCLUSION: Overall, this work suggests that the Ubi and ARP can be useful as reference genes in qRT-PCR examination of gene expression studying wild populations of Atlantic cod.",2008 Jul 16,"['Olsvik, Pål A', 'Søfteland, Liv', 'Lie, Kai K']",BMC Res Notes,,,True
524020333ab93c945ffd02838cb08672703724c1,PMC,Lentivirus Display: Stable Expression of Human Antibodies on the Surface of Human Cells and Virus Particles,http://dx.doi.org/10.1371/journal.pone.0003181,PMC2527531,18784843,CC BY,"BACKGROUND: Isolation of human antibodies using current display technologies can be limited by constraints on protein expression, folding and post-translational modifications. Here we describe a discovery platform that utilizes self-inactivating (SIN) lentiviral vectors for the surface display of high-affinity single-chain variable region (scFv) antibody fragments on human cells and lentivirus particles. METHODOLOGY/PRINCIPAL FINDINGS: Bivalent scFvFc human antibodies were fused in frame with different transmembrane (TM) anchoring moieties to allow efficient high-level expression on human cells and the optimal TM was identified. The addition of an eight amino acid HIV-1 gp41 envelope incorporation motif further increased scFvFc expression on human cells and incorporation into lentiviral particles. Both antibody-displaying human cells and virus particles bound antigen specifically. Sulfation of CDR tyrosine residues, a property recently shown to broaden antibody binding affinity and antigen recognition was also demonstrated. High level scFvFc expression and stable integration was achieved in human cells following transduction with IRES containing bicistronic SIN lentivectors encoding ZsGreen when scFvFc fusion proteins were expressed from the first cassette. Up to 10(6)-fold enrichment of antibody expressing cells was achieved with one round of antigen coupled magnetic bead pre-selection followed by FACS sorting. Finally, the scFvFc displaying human cells could be used directly in functional biological screens with remarkable sensitivity. CONCLUSIONS/SIGNIFICANCE: This antibody display platform will complement existing technologies by virtue of providing properties unique to lentiviruses and antibody expression in human cells, which, in turn, may aid the discovery of novel therapeutic human mAbs.",2008 Sep 11,"['Taube, Ran', 'Zhu, Quan', 'Xu, Chen', 'Diaz-Griffero, Felipe', 'Sui, Jianhua', 'Kamau, Erick', 'Dwyer, Markryan', 'Aird, Daniel', 'Marasco, Wayne A.']",PLoS One,,,True
2afcf2ab2330cb56ec493f82d87fa0c5b5f076e9,PMC,Improving antibiotic prescribing for adults with community acquired pneumonia: Does a computerised decision support system achieve more than academic detailing alone? – a time series analysis,http://dx.doi.org/10.1186/1472-6947-8-35,PMC2527556,18667084,CC BY,"BACKGROUND: The ideal method to encourage uptake of clinical guidelines in hospitals is not known. Several strategies have been suggested. This study evaluates the impact of academic detailing and a computerised decision support system (CDSS) on clinicians' prescribing behaviour for patients with community acquired pneumonia (CAP). METHODS: The management of all patients presenting to the emergency department over three successive time periods was evaluated; the baseline, academic detailing and CDSS periods. The rate of empiric antibiotic prescribing that was concordant with recommendations was studied over time comparing pre and post periods and using an interrupted time series analysis. RESULTS: The odds ratio for concordant therapy in the academic detailing period, after adjustment for age, illness severity and suspicion of aspiration, compared with the baseline period was OR = 2.79 [1.88, 4.14], p < 0.01, and for the computerised decision support period compared to the academic detailing period was OR = 1.99 [1.07, 3.69], p = 0.02. During the first months of the computerised decision support period an improvement in the appropriateness of antibiotic prescribing was demonstrated, which was greater than that expected to have occurred with time and academic detailing alone, based on predictions from a binary logistic model. CONCLUSION: Deployment of a computerised decision support system was associated with an early improvement in antibiotic prescribing practices which was greater than the changes seen with academic detailing. The sustainability of this intervention requires further evaluation.",2008 Jul 31,"['Buising, Kirsty L', 'Thursky, Karin A', 'Black, James F', 'MacGregor, Lachlan', 'Street, Alan C', 'Kennedy, Marcus P', 'Brown, Graham V']",BMC Med Inform Decis Mak,,,True
b890aa8cb8a15fec0f4bb8e970f5a21fd2dfda33,PMC,Loop-mediated isothermal amplification as an emerging technology for detection of Yersinia ruckeri the causative agent of enteric red mouth disease in fish,http://dx.doi.org/10.1186/1746-6148-4-31,PMC2531098,18700011,CC BY,"BACKGROUND: Enteric Redmouth (ERM) disease also known as Yersiniosis is a contagious disease affecting salmonids, mainly rainbow trout. The causative agent is the gram-negative bacterium Yersinia ruckeri. The disease can be diagnosed by isolation and identification of the causative agent, or detection of the Pathogen using fluorescent antibody tests, ELISA and PCR assays. These diagnostic methods are laborious, time consuming and need well trained personnel. RESULTS: A loop-mediated isothermal amplification (LAMP) assay was developed and evaluated for detection of Y. ruckeri the etiological agent of enteric red mouth (ERM) disease in salmonids. The assay was optimised to amplify the yruI/yruR gene, which encodes Y. ruckeri quorum sensing system, in the presence of a specific primer set and Bst DNA polymerase at an isothermal temperature of 63°C for one hour. Amplification products were detected by visual inspection, agarose gel electrophoresis and by real-time monitoring of turbidity resulted by formation of LAMP amplicons. Digestion with HphI restriction enzyme demonstrated that the amplified product was unique. The specificity of the assay was verified by the absence of amplification products when tested against related bacteria. The assay had 10-fold higher sensitivity compared with conventional PCR and successfully detected Y. ruckeri not only in pure bacterial culture but also in tissue homogenates of infected fish. CONCLUSION: The ERM-LAMP assay represents a practical alternative to the microbiological approach for rapid, sensitive and specific detection of Y. ruckeri in fish farms. The assay is carried out in one hour and needs only a heating block or water bath as laboratory furniture. The advantages of the ERM-LAMP assay make it a promising tool for molecular detection of enteric red mouth disease in fish farms.",2008 Aug 12,"['Saleh, Mona', 'Soliman, Hatem', 'El-Matbouli, Mansour']",BMC Vet Res,,,True
3df8818685d06d65f93674101b8ca899731efc36,PMC,Rabies trend in China (1990–2007) and post-exposure prophylaxis in the Guangdong province,http://dx.doi.org/10.1186/1471-2334-8-113,PMC2532688,18717989,CC BY,"BACKGROUND: Rabies is a major public-health problem in developing countries such as China. Although the recent re-emergence of human rabies in China was noted in several epidemiological studies, little attention was paid to the reasons behind this phenomenon paralleling the findings of the previous reports. The purpose of this study is thus first to characterize the current trends of human rabies in China from 1990 to 2007, and then to define better recommendations for improving the post-exposure prophylaxis (PEP) schedules delivered to rabies patients. METHODS: The most updated epidemiological data for 22527 human rabies cases from January 1990 to July 2007, retrieved from the surveillance database of reportable diseases managed by the Ministry of Health of China, were analysed. To investigate the efficiency for the post-exposure treatment of rabies, the details of 244 rabies patients, including their anti-rabies treatment of injuries or related incidents, were ascertained in Guangdong provincial jurisdiction. The risk factors to which the patients were predisposed or the regimens given to 80 patients who received any type of PEP were analysed to identify the reasons for the PEP failures. RESULTS: The results from analysis of the large number of human rabies cases showed that rabies in China was largely under control during the period 1990–1996. However, there has been a large jump in the number of reported rabies cases since 2001 up to a new peak (with an incidence rate of 0.20 per 100000 people) that was reached in 2004, and where the level has remained until present. Then, we analysed the PEP in 244 rabies cases collected in the Guangdong province in 2003 and 2004, and found that 67.2% of the patients did not seek medical services or did not receive any PEP. Further analysis of PEP for the 80 rabies patients who received any type of PEP indicated that almost all of the patients did not receive proper or timely treatment on the wounds or post-exposure vaccination or rabies immunoglobulins. CONCLUSION: While the issue of under-reporting of rabies in previous years may well be a factor in the apparent upwards trend of human rabies in recent years, the analysis of PEP in the Guangdong province provides evidence that suggests that the failure to receive PEP was a major factor in the number of human cases in China. Thus, the data underline the need for greatly improved availability and timely application of high-quality anti-rabies biologicals, both vaccines and immunoglobulins, in the treatment of human bite victims. Controlling dog rabies through pet vaccination schemes may also play a huge role in reducing the rate of human exposure. Education of the public, health care staff and veterinarians will also help to change the current situation.",2008 Aug 21,"['Si, Han', 'Guo, Zhong-Min', 'Hao, Yuan-Tao', 'Liu, Yu-Ge', 'Zhang, Ding-Mei', 'Rao, Shao-Qi', 'Lu, Jia-Hai']",BMC Infect Dis,,,True
4d0b62b91c66f47c6aff69dfa0ed2c25ffe064ae,PMC,Rapid Identification of Known and New RNA Viruses from Animal Tissues,http://dx.doi.org/10.1371/journal.ppat.1000163,PMC2533695,18818738,CC BY,"Viral surveillance programs or diagnostic labs occasionally obtain infectious samples that fail to be typed by available cell culture, serological, or nucleic acid tests. Five such samples, originating from insect pools, skunk brain, human feces and sewer effluent, collected between 1955 and 1980, resulted in pathology when inoculated into suckling mice. In this study, sequence-independent amplification of partially purified viral nucleic acids and small scale shotgun sequencing was used on mouse brain and muscle tissues. A single viral agent was identified in each sample. For each virus, between 16% to 57% of the viral genome was acquired by sequencing only 42–108 plasmid inserts. Viruses derived from human feces or sewer effluent belonged to the Picornaviridae family and showed between 80% to 91% amino acid identities to known picornaviruses. The complete polyprotein sequence of one virus showed strong similarity to a simian picornavirus sequence in the provisional Sapelovirus genus. Insects and skunk derived viral sequences exhibited amino acid identities ranging from 25% to 98% to the segmented genomes of viruses within the Reoviridae family. Two isolates were highly divergent: one is potentially a new species within the orthoreovirus genus, and the other is a new species within the orbivirus genus. We demonstrate that a simple, inexpensive, and rapid metagenomics approach is effective for identifying known and highly divergent new viruses in homogenized tissues of acutely infected mice.",2008 Sep 26,"['Victoria, Joseph G.', 'Kapoor, Amit', 'Dupuis, Kent', 'Schnurr, David P.', 'Delwart, Eric L.']",PLoS Pathog,,,True
82ef5d93dc7dd6b35e8411969e33633b402e5acc,PMC,SARS-Coronavirus Replication Is Supported by a Reticulovesicular Network of Modified Endoplasmic Reticulum,http://dx.doi.org/10.1371/journal.pbio.0060226,PMC2535663,18798692,CC BY,"Positive-strand RNA viruses, a large group including human pathogens such as SARS-coronavirus (SARS-CoV), replicate in the cytoplasm of infected host cells. Their replication complexes are commonly associated with modified host cell membranes. Membrane structures supporting viral RNA synthesis range from distinct spherular membrane invaginations to more elaborate webs of packed membranes and vesicles. Generally, their ultrastructure, morphogenesis, and exact role in viral replication remain to be defined. Poorly characterized double-membrane vesicles (DMVs) were previously implicated in SARS-CoV RNA synthesis. We have now applied electron tomography of cryofixed infected cells for the three-dimensional imaging of coronavirus-induced membrane alterations at high resolution. Our analysis defines a unique reticulovesicular network of modified endoplasmic reticulum that integrates convoluted membranes, numerous interconnected DMVs (diameter 200–300 nm), and “vesicle packets” apparently arising from DMV merger. The convoluted membranes were most abundantly immunolabeled for viral replicase subunits. However, double-stranded RNA, presumably revealing the site of viral RNA synthesis, mainly localized to the DMV interior. Since we could not discern a connection between DMV interior and cytosol, our analysis raises several questions about the mechanism of DMV formation and the actual site of SARS-CoV RNA synthesis. Our data document the extensive virus-induced reorganization of host cell membranes into a network that is used to organize viral replication and possibly hide replicating RNA from antiviral defense mechanisms. Together with biochemical studies of the viral enzyme complex, our ultrastructural description of this “replication network” will aid to further dissect the early stages of the coronavirus life cycle and its virus-host interactions.",2008 Sep 16,"['Knoops, Kèvin', 'Kikkert, Marjolein', 'van den Worm, Sjoerd H. E.', 'Zevenhoven-Dobbe, Jessika C', 'van der Meer, Yvonne', 'Koster, Abraham J', 'Mommaas, A. Mieke', 'Snijder, Eric J']",PLoS Biol,,,True
155cca2a90a5430ac391b46983efa4c13f193289,PMC,Phi29 polymerase based random amplification of viral RNA as an alternative to random RT-PCR,http://dx.doi.org/10.1186/1471-2199-9-77,PMC2535778,18771595,CC BY,"BACKGROUND: Phi29 polymerase based amplification methods provides amplified DNA with minimal changes in sequence and relative abundance for many biomedical applications. RNA virus detection using microarrays, however, can present a challenge because phi29 DNA polymerase cannot amplify RNA nor small cDNA fragments (<2000 bases) obtained by reverse transcription of certain viral RNA genomes. Therefore, ligation of cDNA fragments is necessary prior phi29 polymerase based amplification. We adapted the QuantiTect Whole Transcriptome Kit (Qiagen) to our purposes and designated the method as Whole Transcriptome Amplification (WTA). RESULTS: WTA successfully amplified cDNA from a panel of RNA viruses representing the diversity of ribovirus genome sizes. We amplified a range of genome copy numbers from 15 to 4 × 10(7 )using WTA, which yielded quantities of amplified DNA as high as 1.2 μg/μl or 10(10 )target copies. The amplification factor varied between 10(9 )and 10(6). We also demonstrated that co-amplification occurred when viral RNA was mixed with bacterial DNA. CONCLUSION: This is the first report in the scientific literature showing that a modified WGA (WTA) approach can be successfully applied to viral genomic RNA of all sizes. Amplifying viral RNA by WTA provides considerably better sensitivity and accuracy of detection compared to random RT-PCR.",2008 Sep 4,"['Berthet, Nicolas', 'Reinhardt, Anita K', 'Leclercq, India', 'van Ooyen, Sven', 'Batéjat, Christophe', 'Dickinson, Philip', 'Stamboliyska, Rayna', 'Old, Iain G', 'Kong, Katherine A', 'Dacheux, Laurent', 'Bourhy, Hervé', 'Kennedy, Giulia C', 'Korfhage, Christian', 'Cole, Stewart T', 'Manuguerra, Jean-Claude']",BMC Mol Biol,,,True
06cf324e3d0f793e5c722894c6ea6949655b1f10,PMC,Development of human antibody fragments using antibody phage display for the detection and diagnosis of Venezuelan equine encephalitis virus (VEEV),http://dx.doi.org/10.1186/1472-6750-8-66,PMC2543005,18764933,CC BY,"BACKGROUND: Venezuelan equine encephalitis virus (VEEV) belongs to the Alphavirus group. Several species of this family are also pathogenic to humans and are recognized as potential agents of biological warfare and terrorism. The objective of this work was the generation of recombinant antibodies for the detection of VEEV after a potential bioterrorism assault or an natural outbreak of VEEV. RESULTS: In this work, human anti-VEEV single chain Fragments variable (scFv) were isolated for the first time from a human naïve antibody gene library using optimized selection processes. In total eleven different scFvs were identified and their immunological specificity was assessed. The specific detection of the VEEV strains TC83, H12/93 and 230 by the selected antibody fragments was proved. Active as well as formalin inactivated virus particles were recognized by the selected antibody fragments which could be also used for Western blot analysis of VEEV proteins and immunohistochemistry of VEEV infected cells. The anti-VEEV scFv phage clones did not show any cross-reactivity with Alphavirus species of the Western equine encephalitis virus (WEEV) and Eastern equine encephalitis virus (EEEV) antigenic complex, nor did they react with Chikungunya virus (CHIKV), if they were used as detection reagent. CONCLUSION: For the first time, this study describes the selection of antibodies against a human pathogenic virus from a human naïve scFv antibody gene library using complete, active virus particles as antigen. The broad and sensitive applicability of scFv-presenting phage for the immunological detection and diagnosis of Alphavirus species was demonstrated. The selected antibody fragments will improve the fast identification of VEEV in case of a biological warfare or terroristic attack or a natural outbreak.",2008 Sep 2,"['Kirsch, Martina Inga', 'Hülseweh, Birgit', 'Nacke, Christoph', 'Rülker, Torsten', 'Schirrmann, Thomas', 'Marschall, Hans-Jürgen', 'Hust, Michael', 'Dübel, Stefan']",BMC Biotechnol,,,True
52264dd990e495e82f511cfa80a14b52ec063722,PMC,Control of asthma triggers in indoor air with air cleaners: a modeling analysis,http://dx.doi.org/10.1186/1476-069X-7-43,PMC2543006,18684328,CC BY,"BACKGROUND: Reducing exposure to environmental agents indoors shown to increase asthma symptoms or lead to asthma exacerbations is an important component of a strategy to manage asthma for individuals. Numerous investigations have demonstrated that portable air cleaning devices can reduce concentrations of asthma triggers in indoor air; however, their benefits for breathing problems have not always been reproducible. The potential exposure benefits of whole house high efficiency in-duct air cleaners for sensitive subpopulations have yet to be evaluated. METHODS: We used an indoor air quality modeling system (CONTAM) developed by NIST to examine peak and time-integrated concentrations of common asthma triggers present in indoor air over a year as a function of natural ventilation, portable air cleaners, and forced air ventilation equipped with conventional and high efficiency filtration systems. Emission rates for asthma triggers were based on experimental studies published in the scientific literature. RESULTS: Forced air systems with high efficiency filtration were found to provide the best control of asthma triggers: 30–55% lower cat allergen levels, 90–99% lower risk of respiratory infection through the inhalation route of exposure, 90–98% lower environmental tobacco smoke (ETS) levels, and 50–75% lower fungal spore levels than the other ventilation/filtration systems considered. These results indicate that the use of high efficiency in-duct air cleaners provide an effective means of controlling allergen levels not only in a single room, like a portable air cleaner, but the whole house. CONCLUSION: These findings are useful for evaluating potential benefits of high efficiency in-duct filtration systems for controlling exposure to asthma triggers indoors and for the design of trials of environmental interventions intended to evaluate their utility in practice.",2008 Aug 6,"['Myatt, Theodore A', 'Minegishi, Taeko', 'Allen, Joseph G', 'MacIntosh, David L']",Environ Health,,,True
61974b05fc434de7782d10056e719e7d1bdda66d,PMC,Control of asthma triggers in indoor air with air cleaners: a modeling analysis,http://dx.doi.org/10.1186/1476-069X-7-43,PMC2543006,18684328,CC BY,"BACKGROUND: Reducing exposure to environmental agents indoors shown to increase asthma symptoms or lead to asthma exacerbations is an important component of a strategy to manage asthma for individuals. Numerous investigations have demonstrated that portable air cleaning devices can reduce concentrations of asthma triggers in indoor air; however, their benefits for breathing problems have not always been reproducible. The potential exposure benefits of whole house high efficiency in-duct air cleaners for sensitive subpopulations have yet to be evaluated. METHODS: We used an indoor air quality modeling system (CONTAM) developed by NIST to examine peak and time-integrated concentrations of common asthma triggers present in indoor air over a year as a function of natural ventilation, portable air cleaners, and forced air ventilation equipped with conventional and high efficiency filtration systems. Emission rates for asthma triggers were based on experimental studies published in the scientific literature. RESULTS: Forced air systems with high efficiency filtration were found to provide the best control of asthma triggers: 30–55% lower cat allergen levels, 90–99% lower risk of respiratory infection through the inhalation route of exposure, 90–98% lower environmental tobacco smoke (ETS) levels, and 50–75% lower fungal spore levels than the other ventilation/filtration systems considered. These results indicate that the use of high efficiency in-duct air cleaners provide an effective means of controlling allergen levels not only in a single room, like a portable air cleaner, but the whole house. CONCLUSION: These findings are useful for evaluating potential benefits of high efficiency in-duct filtration systems for controlling exposure to asthma triggers indoors and for the design of trials of environmental interventions intended to evaluate their utility in practice.",2008 Aug 6,"['Myatt, Theodore A', 'Minegishi, Taeko', 'Allen, Joseph G', 'MacIntosh, David L']",Environ Health,,,False
f818f2753bb690f66cdd53852c07db6e0c1d46f3,PMC,Control of asthma triggers in indoor air with air cleaners: a modeling analysis,http://dx.doi.org/10.1186/1476-069X-7-43,PMC2543006,18684328,CC BY,"BACKGROUND: Reducing exposure to environmental agents indoors shown to increase asthma symptoms or lead to asthma exacerbations is an important component of a strategy to manage asthma for individuals. Numerous investigations have demonstrated that portable air cleaning devices can reduce concentrations of asthma triggers in indoor air; however, their benefits for breathing problems have not always been reproducible. The potential exposure benefits of whole house high efficiency in-duct air cleaners for sensitive subpopulations have yet to be evaluated. METHODS: We used an indoor air quality modeling system (CONTAM) developed by NIST to examine peak and time-integrated concentrations of common asthma triggers present in indoor air over a year as a function of natural ventilation, portable air cleaners, and forced air ventilation equipped with conventional and high efficiency filtration systems. Emission rates for asthma triggers were based on experimental studies published in the scientific literature. RESULTS: Forced air systems with high efficiency filtration were found to provide the best control of asthma triggers: 30–55% lower cat allergen levels, 90–99% lower risk of respiratory infection through the inhalation route of exposure, 90–98% lower environmental tobacco smoke (ETS) levels, and 50–75% lower fungal spore levels than the other ventilation/filtration systems considered. These results indicate that the use of high efficiency in-duct air cleaners provide an effective means of controlling allergen levels not only in a single room, like a portable air cleaner, but the whole house. CONCLUSION: These findings are useful for evaluating potential benefits of high efficiency in-duct filtration systems for controlling exposure to asthma triggers indoors and for the design of trials of environmental interventions intended to evaluate their utility in practice.",2008 Aug 6,"['Myatt, Theodore A', 'Minegishi, Taeko', 'Allen, Joseph G', 'MacIntosh, David L']",Environ Health,,,False
43f0ed0ead4058d6f92c7390c15d0d9fe66af448,PMC,Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: Identification of a candidate etiologic agent,http://dx.doi.org/10.1186/1743-422X-5-88,PMC2546392,18671869,CC BY,"BACKGROUND: Proventricular dilatation disease (PDD) is a fatal disorder threatening domesticated and wild psittacine birds worldwide. It is characterized by lymphoplasmacytic infiltration of the ganglia of the central and peripheral nervous system, leading to central nervous system disorders as well as disordered enteric motility and associated wasting. For almost 40 years, a viral etiology for PDD has been suspected, but to date no candidate etiologic agent has been reproducibly linked to the disease. RESULTS: Analysis of 2 PDD case-control series collected independently on different continents using a pan-viral microarray revealed a bornavirus hybridization signature in 62.5% of the PDD cases (5/8) and none of the controls (0/8). Ultra high throughput sequencing was utilized to recover the complete viral genome sequence from one of the virus-positive PDD cases. This revealed a bornavirus-like genome organization for this agent with a high degree of sequence divergence from all prior bornavirus isolates. We propose the name avian bornavirus (ABV) for this agent. Further specific ABV PCR analysis of an additional set of independently collected PDD cases and controls yielded a significant difference in ABV detection rate among PDD cases (71%, n = 7) compared to controls (0%, n = 14) (P = 0.01; Fisher's Exact Test). Partial sequence analysis of a total of 16 ABV isolates we have now recovered from these and an additional set of cases reveals at least 5 distinct ABV genetic subgroups. CONCLUSION: These studies clearly demonstrate the existence of an avian reservoir of remarkably diverse bornaviruses and provide a compelling candidate in the search for an etiologic agent of PDD.",2008 Jul 31,"['Kistler, Amy L', 'Gancz, Ady', 'Clubb, Susan', 'Skewes-Cox, Peter', 'Fischer, Kael', 'Sorber, Katherine', 'Chiu, Charles Y', 'Lublin, Avishai', 'Mechani, Sara', 'Farnoushi, Yigal', 'Greninger, Alexander', 'Wen, Christopher C', 'Karlene, Scott B', 'Ganem, Don', 'DeRisi, Joseph L']",Virol J,,,True
15cded6cc0f782faabb4abb5dfd91c48a831e2a3,PMC,Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: Identification of a candidate etiologic agent,http://dx.doi.org/10.1186/1743-422X-5-88,PMC2546392,18671869,CC BY,"BACKGROUND: Proventricular dilatation disease (PDD) is a fatal disorder threatening domesticated and wild psittacine birds worldwide. It is characterized by lymphoplasmacytic infiltration of the ganglia of the central and peripheral nervous system, leading to central nervous system disorders as well as disordered enteric motility and associated wasting. For almost 40 years, a viral etiology for PDD has been suspected, but to date no candidate etiologic agent has been reproducibly linked to the disease. RESULTS: Analysis of 2 PDD case-control series collected independently on different continents using a pan-viral microarray revealed a bornavirus hybridization signature in 62.5% of the PDD cases (5/8) and none of the controls (0/8). Ultra high throughput sequencing was utilized to recover the complete viral genome sequence from one of the virus-positive PDD cases. This revealed a bornavirus-like genome organization for this agent with a high degree of sequence divergence from all prior bornavirus isolates. We propose the name avian bornavirus (ABV) for this agent. Further specific ABV PCR analysis of an additional set of independently collected PDD cases and controls yielded a significant difference in ABV detection rate among PDD cases (71%, n = 7) compared to controls (0%, n = 14) (P = 0.01; Fisher's Exact Test). Partial sequence analysis of a total of 16 ABV isolates we have now recovered from these and an additional set of cases reveals at least 5 distinct ABV genetic subgroups. CONCLUSION: These studies clearly demonstrate the existence of an avian reservoir of remarkably diverse bornaviruses and provide a compelling candidate in the search for an etiologic agent of PDD.",2008 Jul 31,"['Kistler, Amy L', 'Gancz, Ady', 'Clubb, Susan', 'Skewes-Cox, Peter', 'Fischer, Kael', 'Sorber, Katherine', 'Chiu, Charles Y', 'Lublin, Avishai', 'Mechani, Sara', 'Farnoushi, Yigal', 'Greninger, Alexander', 'Wen, Christopher C', 'Karlene, Scott B', 'Ganem, Don', 'DeRisi, Joseph L']",Virol J,,,False
a2c3e84cdf13b1c02cdeb286515e4745d33bfc10,PMC,Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: Identification of a candidate etiologic agent,http://dx.doi.org/10.1186/1743-422X-5-88,PMC2546392,18671869,CC BY,"BACKGROUND: Proventricular dilatation disease (PDD) is a fatal disorder threatening domesticated and wild psittacine birds worldwide. It is characterized by lymphoplasmacytic infiltration of the ganglia of the central and peripheral nervous system, leading to central nervous system disorders as well as disordered enteric motility and associated wasting. For almost 40 years, a viral etiology for PDD has been suspected, but to date no candidate etiologic agent has been reproducibly linked to the disease. RESULTS: Analysis of 2 PDD case-control series collected independently on different continents using a pan-viral microarray revealed a bornavirus hybridization signature in 62.5% of the PDD cases (5/8) and none of the controls (0/8). Ultra high throughput sequencing was utilized to recover the complete viral genome sequence from one of the virus-positive PDD cases. This revealed a bornavirus-like genome organization for this agent with a high degree of sequence divergence from all prior bornavirus isolates. We propose the name avian bornavirus (ABV) for this agent. Further specific ABV PCR analysis of an additional set of independently collected PDD cases and controls yielded a significant difference in ABV detection rate among PDD cases (71%, n = 7) compared to controls (0%, n = 14) (P = 0.01; Fisher's Exact Test). Partial sequence analysis of a total of 16 ABV isolates we have now recovered from these and an additional set of cases reveals at least 5 distinct ABV genetic subgroups. CONCLUSION: These studies clearly demonstrate the existence of an avian reservoir of remarkably diverse bornaviruses and provide a compelling candidate in the search for an etiologic agent of PDD.",2008 Jul 31,"['Kistler, Amy L', 'Gancz, Ady', 'Clubb, Susan', 'Skewes-Cox, Peter', 'Fischer, Kael', 'Sorber, Katherine', 'Chiu, Charles Y', 'Lublin, Avishai', 'Mechani, Sara', 'Farnoushi, Yigal', 'Greninger, Alexander', 'Wen, Christopher C', 'Karlene, Scott B', 'Ganem, Don', 'DeRisi, Joseph L']",Virol J,,,False
28619df1e1f9d348dd517aeb7d20e7c4bfa5790a,PMC,Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: Identification of a candidate etiologic agent,http://dx.doi.org/10.1186/1743-422X-5-88,PMC2546392,18671869,CC BY,"BACKGROUND: Proventricular dilatation disease (PDD) is a fatal disorder threatening domesticated and wild psittacine birds worldwide. It is characterized by lymphoplasmacytic infiltration of the ganglia of the central and peripheral nervous system, leading to central nervous system disorders as well as disordered enteric motility and associated wasting. For almost 40 years, a viral etiology for PDD has been suspected, but to date no candidate etiologic agent has been reproducibly linked to the disease. RESULTS: Analysis of 2 PDD case-control series collected independently on different continents using a pan-viral microarray revealed a bornavirus hybridization signature in 62.5% of the PDD cases (5/8) and none of the controls (0/8). Ultra high throughput sequencing was utilized to recover the complete viral genome sequence from one of the virus-positive PDD cases. This revealed a bornavirus-like genome organization for this agent with a high degree of sequence divergence from all prior bornavirus isolates. We propose the name avian bornavirus (ABV) for this agent. Further specific ABV PCR analysis of an additional set of independently collected PDD cases and controls yielded a significant difference in ABV detection rate among PDD cases (71%, n = 7) compared to controls (0%, n = 14) (P = 0.01; Fisher's Exact Test). Partial sequence analysis of a total of 16 ABV isolates we have now recovered from these and an additional set of cases reveals at least 5 distinct ABV genetic subgroups. CONCLUSION: These studies clearly demonstrate the existence of an avian reservoir of remarkably diverse bornaviruses and provide a compelling candidate in the search for an etiologic agent of PDD.",2008 Jul 31,"['Kistler, Amy L', 'Gancz, Ady', 'Clubb, Susan', 'Skewes-Cox, Peter', 'Fischer, Kael', 'Sorber, Katherine', 'Chiu, Charles Y', 'Lublin, Avishai', 'Mechani, Sara', 'Farnoushi, Yigal', 'Greninger, Alexander', 'Wen, Christopher C', 'Karlene, Scott B', 'Ganem, Don', 'DeRisi, Joseph L']",Virol J,,,False
a2e4c6efa8b851cd3519485c77941d2ec4c4b15c,PMC,Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: Identification of a candidate etiologic agent,http://dx.doi.org/10.1186/1743-422X-5-88,PMC2546392,18671869,CC BY,"BACKGROUND: Proventricular dilatation disease (PDD) is a fatal disorder threatening domesticated and wild psittacine birds worldwide. It is characterized by lymphoplasmacytic infiltration of the ganglia of the central and peripheral nervous system, leading to central nervous system disorders as well as disordered enteric motility and associated wasting. For almost 40 years, a viral etiology for PDD has been suspected, but to date no candidate etiologic agent has been reproducibly linked to the disease. RESULTS: Analysis of 2 PDD case-control series collected independently on different continents using a pan-viral microarray revealed a bornavirus hybridization signature in 62.5% of the PDD cases (5/8) and none of the controls (0/8). Ultra high throughput sequencing was utilized to recover the complete viral genome sequence from one of the virus-positive PDD cases. This revealed a bornavirus-like genome organization for this agent with a high degree of sequence divergence from all prior bornavirus isolates. We propose the name avian bornavirus (ABV) for this agent. Further specific ABV PCR analysis of an additional set of independently collected PDD cases and controls yielded a significant difference in ABV detection rate among PDD cases (71%, n = 7) compared to controls (0%, n = 14) (P = 0.01; Fisher's Exact Test). Partial sequence analysis of a total of 16 ABV isolates we have now recovered from these and an additional set of cases reveals at least 5 distinct ABV genetic subgroups. CONCLUSION: These studies clearly demonstrate the existence of an avian reservoir of remarkably diverse bornaviruses and provide a compelling candidate in the search for an etiologic agent of PDD.",2008 Jul 31,"['Kistler, Amy L', 'Gancz, Ady', 'Clubb, Susan', 'Skewes-Cox, Peter', 'Fischer, Kael', 'Sorber, Katherine', 'Chiu, Charles Y', 'Lublin, Avishai', 'Mechani, Sara', 'Farnoushi, Yigal', 'Greninger, Alexander', 'Wen, Christopher C', 'Karlene, Scott B', 'Ganem, Don', 'DeRisi, Joseph L']",Virol J,,,False
0a00a6df208e068e7aa369fb94641434ea0e6070,PMC,Novel genome polymorphisms in BCG vaccine strains and impact on efficacy,http://dx.doi.org/10.1186/1471-2164-9-413,PMC2553098,18793412,CC BY,"Bacille Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis currently used as a vaccine against tuberculosis. Global distribution and propagation of BCG has contributed to the in vitro evolution of the vaccine strain and is thought to partially account for the different outcomes of BCG vaccine trials. Previous efforts by several molecular techniques effectively identified large sequence polymorphisms among BCG daughter strains, but lacked the resolution to identify smaller changes. In this study, we have used a NimbleGen tiling array for whole genome comparison of 13 BCG strains. Using this approach, in tandem with DNA resequencing, we have identified six novel large sequence polymorphisms including four deletions and two duplications in specific BCG strains. Moreover, we have uncovered various polymorphisms in the phoP-phoR locus. Importantly, these polymorphisms affect genes encoding established virulence factors including cell wall complex lipids, ESX secretion systems, and the PhoP-PhoR two-component system. Our study demonstrates that major virulence factors are different among BCG strains, which provide molecular mechanisms for important vaccine phenotypes including adverse effect profile, tuberculin reactivity and protective efficacy. These findings have important implications for the development of a new generation of vaccines.",2008 Sep 15,"['Leung, Andrea S', 'Tran, Vanessa', 'Wu, Zuowei', 'Yu, Xuping', 'Alexander, David C', 'Gao, George Fu', 'Zhu, Baoli', 'Liu, Jun']",BMC Genomics,,,True
bbbeb27419905cbacf36b6932302650784570099,PMC,Genome-Wide Analysis of Protein-Protein Interactions and Involvement of Viral Proteins in SARS-CoV Replication,http://dx.doi.org/10.1371/journal.pone.0003299,PMC2553179,18827877,CC BY,"Analyses of viral protein-protein interactions are an important step to understand viral protein functions and their underlying molecular mechanisms. In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV) and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Three pairs of the interactions identified were detected in both directions: non-structural protein (nsp) 10 and nsp14, nsp10 and nsp16, and nsp7 and nsp8. The interactions between the multifunctional nsp10 and nsp14 or nsp16, which are the unique proteins found in the members of Nidovirales with large RNA genomes including coronaviruses and toroviruses, may have important implication for the mechanisms of replication/transcription complex assembly and functions of these viruses. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12) provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. Collectively, our findings provide a basis and platform for further characterization of the functions and mechanisms of coronavirus proteins.",2008 Oct 1,"[""Pan, Ji'An"", 'Peng, Xiaoxue', 'Gao, Yajing', 'Li, Zhilin', 'Lu, Xiaolu', 'Chen, Yingzhao', 'Ishaq, Musarat', 'Liu, Dan', 'DeDiego, Marta L.', 'Enjuanes, Luis', 'Guo, Deyin']",PLoS One,,,True
010ad052b58172981e089bc73b9ad16a732960f2,PMC,Activation of the Unfolded Protein Response Is Required for Defenses against Bacterial Pore-Forming Toxin In Vivo,http://dx.doi.org/10.1371/journal.ppat.1000176,PMC2553261,18846208,CC BY,"Pore-forming toxins (PFTs) constitute the single largest class of proteinaceous bacterial virulence factors and are made by many of the most important bacterial pathogens. Host responses to these toxins are complex and poorly understood. We find that the endoplasmic reticulum unfolded protein response (UPR) is activated upon exposure to PFTs both in Caenorhabditis elegans and in mammalian cells. Activation of the UPR is protective in vivo against PFTs since animals that lack either the ire-1-xbp-1 or the atf-6 arms of the UPR are more sensitive to PFT than wild-type animals. The UPR acts directly in the cells targeted by the PFT. Loss of the UPR leads to a normal response against unrelated toxins or a pathogenic bacterium, indicating its PFT-protective role is specific. The p38 mitogen-activated protein (MAPK) kinase pathway has been previously shown to be important for cellular defenses against PFTs. We find here that the UPR is one of the key downstream targets of the p38 MAPK pathway in response to PFT since loss of a functional p38 MAPK pathway leads to a failure of PFT to properly activate the ire-1-xbp-1 arm of the UPR. The UPR-mediated activation and response to PFTs is distinct from the canonical UPR-mediated response to unfolded proteins both in terms of its activation and functional sensitivities. These data demonstrate that the UPR, a fundamental intracellular pathway, can operate in intrinsic cellular defenses against bacterial attack.",2008 Oct 10,"['Bischof, Larry J.', 'Kao, Cheng-Yuan', 'Los, Ferdinand C. O.', 'Gonzalez, Manuel R.', 'Shen, Zhouxin', 'Briggs, Steven P.', 'van der Goot, F. Gisou', 'Aroian, Raffi V.']",PLoS Pathog,,,True
b19a29c5c29055c01ee2e63ec63a395c0f7ddb17,PMC,LOMA: A fast method to generate efficient tagged-random primers despite amplification bias of random PCR on pathogens,http://dx.doi.org/10.1186/1471-2105-9-368,PMC2553803,18783594,CC BY,"BACKGROUND: Pathogen detection using DNA microarrays has the potential to become a fast and comprehensive diagnostics tool. However, since pathogen detection chips currently utilize random primers rather than specific primers for the RT-PCR step, bias inherent in random PCR amplification becomes a serious problem that causes large inaccuracies in hybridization signals. RESULTS: In this paper, we study how the efficiency of random PCR amplification affects hybridization signals. We describe a model that predicts the amplification efficiency of a given random primer on a target viral genome. The prediction allows us to filter false-negative probes of the genome that lie in regions of poor random PCR amplification and improves the accuracy of pathogen detection. Subsequently, we propose LOMA, an algorithm to generate random primers that have good amplification efficiency. Wet-lab validation showed that the generated random primers improve the amplification efficiency significantly. CONCLUSION: The blind use of a random primer with attached universal tag (random-tagged primer) in a PCR reaction on a pathogen sample may not lead to a successful amplification. Thus, the design of random-tagged primers is an important consideration when performing PCR.",2008 Sep 10,"['Lee, Wah Heng', 'Wong, Christopher W', 'Leong, Wan Yee', 'Miller, Lance D', 'Sung, Wing Kin']",BMC Bioinformatics,,,True
16627f4c7134394da448b1417a771d13ad7cca4a,PMC,Pandemic influenza in Australia: Using telephone surveys to measure perceptions of threat and willingness to comply,http://dx.doi.org/10.1186/1471-2334-8-117,PMC2556339,18793441,CC BY,"BACKGROUND: Baseline data is necessary for monitoring how a population perceives the threat of pandemic influenza, and perceives how it would behave in the event of pandemic influenza. Our aim was to develop a module of questions for use in telephone health surveys on perceptions of threat of pandemic influenza, and on preparedness to comply with specific public health behaviours in the event of pandemic influenza. METHODS: A module of questions was developed and field tested on 192 adults using the New South Wales Department of Health's in-house Computer Assisted Telephone Interviewing (CATI) facility. The questions were then modified and re field tested on 202 adults. The module was then incorporated into the New South Wales Population Health Survey in the first quarter of 2007. A representative sample of 2,081 adults completed the module. Their responses were weighted against the state population. RESULTS: The reliability of the questions was acceptable with kappa ranging between 0.25 and 0.51. Overall 14.9% of the state population thought pandemic influenza was very or extremely likely to occur; 45.5% were very or extremely concerned that they or their family would be affected by pandemic influenza if it occurred; and 23.8% had made some level of change to the way they live their life because of the possibility of pandemic influenza. In the event of pandemic influenza, the majority of the population were willing to: be vaccinated (75.4%), be isolated (70.2%), and wear a face mask (59.9%). People with higher levels of threat perception are significantly more likely to be willing to comply with specific public health behaviours. CONCLUSION: While only 14.9% of the state population thought pandemic influenza was very or extremely likely to occur, a significantly higher proportion were concerned for self and family should a pandemic actually occur. The baseline data collected in this survey will be useful for monitoring changes over time in the population's perceptions of threat, and preparedness to comply with specific public health behaviours.",2008 Sep 15,"['Barr, Margo', 'Raphael, Beverley', 'Taylor, Melanie', 'Stevens, Garry', 'Jorm, Louisa', 'Giffin, Michael', 'Lujic, Sanja']",BMC Infect Dis,,,True
e5c1960487379bc9bd2cdfef08fc1b6e515abf73,PMC,Composition and Function of Haemolymphatic Tissues in the European Common Shrew,http://dx.doi.org/10.1371/journal.pone.0003413,PMC2561066,18923707,CC BY,"BACKGROUND: Studies of wild animals responding to their native parasites are essential if we are to understand how the immune system functions in the natural environment. While immune defence may bring increased survival, this may come at a resource cost to other physiological traits, including reproduction. Here, we tested the hypothesis that wild common shrews (Sorex araneus), which produce large numbers of offspring during the one breeding season of their short life span, forgo investment in immunity and immune system maintenance, as increased longevity is unlikely to bring further opportunities for mating. In particular, we predicted that adult shrews, with shorter expected lifespans, would not respond as effectively as young animals to infection. METHODOLOGY/PRINCIPAL FINDINGS: We examined haemolymphatic tissues from wild-caught common shrews using light and transmission electron microscopy, applied in conjunction with immunohistology. We compared composition and function of these tissues in shrews of different ages, and the extent and type of inflammatory reactions observed in response to natural parasitic infections. All ages seemed able to mount systemic, specific immune responses, but adult shrews showed some signs of lymphatic tissue exhaustion: lymphatic follicles in adults (n = 21) were both smaller than those in sub-adults (n = 18; Wald = 11.1, p<0.05) and exhibited greater levels of depletion (Wald = 13.3, p<0.05). CONCLUSIONS/SIGNIFICANCE: Contrary to our expectations, shrews respond effectively to their natural parasites, and show little indication of immunosenescence as adults. The pancreas of Aselli, a unique lymphoid organ, may aid in providing efficient immune responses through the storage of large numbers of plasma cells. This may allow older animals to react effectively to previously encountered parasites, but infection by novel agents, and eventual depletion of plasma cell reserves, could both still be factors in the near-synchronous mortality of adult shrews observed shortly after breeding.",2008 Oct 15,"['Bray, Daniel P.', 'Bennett, Malcolm', 'Stockley, Paula', 'Hurst, Jane L.', 'Kipar, Anja']",PLoS One,,,True
daffb9a10450c4d9217cf3819a559c31cd49970c,PMC,Prevention of Cytotoxic T Cell Escape Using a Heteroclitic Subdominant Viral T Cell Determinant,http://dx.doi.org/10.1371/journal.ppat.1000186,PMC2563037,18949029,CC BY,"High affinity antigen-specific T cells play a critical role during protective immune responses. Epitope enhancement can elicit more potent T cell responses and can subsequently lead to a stronger memory pool; however, the molecular basis of such enhancement is unclear. We used the consensus peptide-binding motif for the Major Histocompatibility Complex molecule H-2K(b) to design a heteroclitic version of the mouse hepatitis virus-specific subdominant S598 determinant. We demonstrate that a single amino acid substitution at a secondary anchor residue (Q to Y at position 3) increased the stability of the engineered determinant in complex with H-2K(b). The structural basis for this enhanced stability was associated with local alterations in the pMHC conformation as a result of the Q to Y substitution. Recombinant viruses encoding this engineered determinant primed CTL responses that also reacted to the wildtype epitope with significantly higher functional avidity, and protected against selection of virus mutated at a second CTL determinant and consequent disease progression in persistently infected mice. Collectively, our findings provide a basis for the enhanced immunogenicity of an engineered determinant that will serve as a template for guiding the development of heteroclitic T cell determinants with applications in prevention of CTL escape in chronic viral infections as well as in tumor immunity.",2008 Oct 24,"['Butler, Noah S.', 'Theodossis, Alex', 'Webb, Andrew I.', 'Nastovska, Roza', 'Ramarathinam, Sri Harsha', 'Dunstone, Michelle A.', 'Rossjohn, Jamie', 'Purcell, Anthony W.', 'Perlman, Stanley']",PLoS Pathog,,,True
0951f5ec3710990a5c181e04fa8fdf7d9a0376e5,PMC,HIV-Specific T-Cells Accumulate in the Liver in HCV/HIV Co-Infection,http://dx.doi.org/10.1371/journal.pone.0003454,PMC2565067,18941622,CC BY,"BACKGROUND AND AIMS: Hepatitis C Virus (HCV)-related liver disease progresses more rapidly in individuals co-infected with Human Immunodeficiency Virus-1 (HIV), although the underlying immunologic mechanisms are unknown. We examined whether HIV-specific T-cells are identified in the liver of HCV/HIV co-infected individuals and promote liver inflammation through bystander immune responses. METHODS: Ex-vivo intra-hepatic lymphocytes from HCV mono-infected and HCV/HIV co-infected individuals were assessed for immune responses to HIV and HCV antigens by polychromatic flow cytometry. RESULTS: HCV/HIV liver biopsies had similar frequencies of lymphocytes but lower percentages of CD4(+) T-cells compared to HCV biopsies. In co-infection, intra-hepatic HIV-specific CD8(+) and CD4(+) T-cells producing IFN-γ and TNF-α were detected and were comparable in frequency to those that were HCV-specific. In co-infected individuals, viral-specific CD8(+) T-cells produced more of the fibrogenic cytokine, TNF-α. In both mono- and co-infected individuals, intra-hepatic HCV-specific T-cells were poorly functional compared to HIV-specific T-cells. In co-infection, HAART was not associated with a reconstitution of intra-hepatic CD4(+) T-cells and was associated with reduction in both HIV and HCV-specific intra-hepatic cytokine responses. CONCLUSION: The accumulation of functional HIV-specific T-cells in the liver during HCV/HIV co-infection may represent a bystander role for HIV in inducing faster progression of liver disease.",2008 Oct 20,"['Vali, Bahareh', 'Yue, Feng Yun', 'Jones, R. Brad', 'Sheth, Prameet M.', 'Kaul, Rupert', 'Betts, Michael R.', 'Wong, David', 'Kovacs, Colin', 'Loutfy, Mona', 'Common, Andrew', 'Halpenny, Roberta', 'Ostrowski, Mario A.']",PLoS One,,,True
2a98b0a9e3e89d1aff14a6f64e25374b4e2855a8,PMC,Predicting the sensitivity and specificity of published real-time PCR assays,http://dx.doi.org/10.1186/1476-0711-7-18,PMC2566554,18817537,CC BY,"BACKGROUND: In recent years real-time PCR has become a leading technique for nucleic acid detection and quantification. These assays have the potential to greatly enhance efficiency in the clinical laboratory. Choice of primer and probe sequences is critical for accurate diagnosis in the clinic, yet current primer/probe signature design strategies are limited, and signature evaluation methods are lacking. METHODS: We assessed the quality of a signature by predicting the number of true positive, false positive and false negative hits against all available public sequence data. We found real-time PCR signatures described in recent literature and used a BLAST search based approach to collect all hits to the primer-probe combinations that should be amplified by real-time PCR chemistry. We then compared our hits with the sequences in the NCBI taxonomy tree that the signature was designed to detect. RESULTS: We found that many published signatures have high specificity (almost no false positives) but low sensitivity (high false negative rate). Where high sensitivity is needed, we offer a revised methodology for signature design which may designate that multiple signatures are required to detect all sequenced strains. We use this methodology to produce new signatures that are predicted to have higher sensitivity and specificity. CONCLUSION: We show that current methods for real-time PCR assay design have unacceptably low sensitivities for most clinical applications. Additionally, as new sequence data becomes available, old assays must be reassessed and redesigned. A standard protocol for both generating and assessing the quality of these assays is therefore of great value. Real-time PCR has the capacity to greatly improve clinical diagnostics. The improved assay design and evaluation methods presented herein will expedite adoption of this technique in the clinical lab.",2008 Sep 25,"['Lemmon, Gordon H', 'Gardner, Shea N']",Ann Clin Microbiol Antimicrob,,,True
9f9e925d9999ab39745f2ee8be3efffb5277d082,PMC,Molecular evidence for the evolution of ichnoviruses from ascoviruses by symbiogenesis,http://dx.doi.org/10.1186/1471-2148-8-253,PMC2567993,18801176,CC BY,"BACKGROUND: Female endoparasitic ichneumonid wasps inject virus-like particles into their caterpillar hosts to suppress immunity. These particles are classified as ichnovirus virions and resemble ascovirus virions, which are also transmitted by parasitic wasps and attack caterpillars. Ascoviruses replicate DNA and produce virions. Polydnavirus DNA consists of wasp DNA replicated by the wasp from its genome, which also directs particle synthesis. Structural similarities between ascovirus and ichnovirus particles and the biology of their transmission suggest that ichnoviruses evolved from ascoviruses, although molecular evidence for this hypothesis is lacking. RESULTS: Here we show that a family of unique pox-D5 NTPase proteins in the Glypta fumiferanae ichnovirus are related to three Diadromus pulchellus ascovirus proteins encoded by ORFs 90, 91 and 93. A new alignment technique also shows that two proteins from a related ichnovirus are orthologs of other ascovirus virion proteins. CONCLUSION: Our results provide molecular evidence supporting the origin of ichnoviruses from ascoviruses by lateral transfer of ascoviral genes into ichneumonid wasp genomes, perhaps the first example of symbiogenesis between large DNA viruses and eukaryotic organisms. We also discuss the limits of this evidence through complementary studies, which revealed that passive lateral transfer of viral genes among polydnaviral, bacterial, and wasp genomes may have occurred repeatedly through an intimate coupling of both recombination and replication of viral genomes during evolution. The impact of passive lateral transfers on evolutionary relationships between polydnaviruses and viruses with large double-stranded genomes is considered in the context of the theory of symbiogenesis.",2008 Sep 18,"['Bigot, Yves', 'Samain, Sylvie', 'Augé-Gouillou, Corinne', 'Federici, Brian A']",BMC Evol Biol,,,True
dad72c9c3422ef1c9b9149e8dd567de494d46a8a,PMC,Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice,http://dx.doi.org/10.1371/journal.pone.0003548,PMC2569416,18958172,CC BY,"Pre-existing immunity to human adenovirus serotype 5 (Ad5) is common in the general population. Bypassing pre-existing immunity could maximize Ad5 vaccine efficacy. Vaccination by the intramuscular (I.M.), nasal (I.N.) or oral (P.O.) route with Ad5 expressing Ebola Zaire glycoprotein (Ad5-ZGP) fully protected naïve mice against lethal challenge with Ebola. In the presence of pre-existing immunity, only mice vaccinated I.N. survived. The frequency of IFN-γ+ CD8+ T cells was reduced by 80% and by 15% in animals vaccinated by the I.M. and P.O. routes respectively. Neutralizing antibodies could not be detected in serum from either treatment group. Pre-existing immunity did not compromise the frequency of IFN-γ+ CD8+ T cells (3.9±1% naïve vs. 3.6±1% pre-existing immunity, PEI) nor anti-Ebola neutralizing antibody (NAB, 40±10 reciprocal dilution, both groups). The number of INF-γ+ CD8+ cells detected in bronchioalveolar lavage fluid (BAL) after I.N. immunization was not compromised by pre-existing immunity to Ad5 (146±14, naïve vs. 120±16 SFC/million MNCs, PEI). However, pre-existing immunity reduced NAB levels in BAL by ∼25% in this group. To improve the immune response after oral vaccination, the Ad5-based vaccine was PEGylated. Mice given the modified vaccine did not survive challenge and had reduced levels of IFN-γ+ CD8+ T cells 10 days after administration (0.3±0.3% PEG vs. 1.7±0.5% unmodified). PEGylation did increase NAB levels 2-fold. These results provide some insight about the degree of T and B cell mediated immunity necessary for protection against Ebola virus and suggest that modification of the virus capsid can influence the type of immune response elicited by an Ad5-based vaccine.",2008 Oct 29,"['Croyle, Maria A.', 'Patel, Ami', 'Tran, Kaylie N.', 'Gray, Michael', 'Zhang, Yi', 'Strong, James E.', 'Feldmann, Heinz', 'Kobinger, Gary P.']",PLoS One,,,True
9e716720f4daa4c2f5f85df4b4ee6838255d4f80,PMC,Hantaviruses and TNF-alpha act synergistically to induce ERK1/2 inactivation in Vero E6 cells,http://dx.doi.org/10.1186/1743-422X-5-110,PMC2569924,18822184,CC BY,"BACKGROUND: We have previously reported that the apathogenic Tula hantavirus induces apoptosis in Vero E6 epithelial cells. To assess the molecular mechanisms behind the induced apoptosis we studied the effects of hantavirus infection on cellular signaling pathways which promote cell survival. We previously also observed that the Tula virus-induced cell death process is augmented by external TNF-α. Since TNF-α is involved in the pathogenesis of hantavirus-caused hemorrhagic fever with renal syndrome (HFRS) we investigated its effects on HFRS-causing hantavirus-infected cells. RESULTS: We studied both apathogenic (Tula and Topografov) and pathogenic (Puumala and Seoul) hantaviruses for their ability to regulate cellular signaling pathways and observed a direct virus-mediated down-regulation of external signal-regulated kinases 1 and 2 (ERK1/2) survival pathway activity, which was dramatically enhanced by TNF-α. The fold of ERK1/2 inhibition correlated with viral replication efficiencies, which varied drastically between the hantaviruses studied. CONCLUSION: We demonstrate that in the presence of a cytokine TNF-α, which is increased in HFRS patients, hantaviruses are capable of inactivating proteins that promote cell survival (ERK1/2). These results imply that hantavirus-infected epithelial cell barrier functions might be compromised in diseased individuals and could at least partially explain the mechanisms of renal dysfunction and the resulting proteinuria seen in HFRS patients.",2008 Sep 29,"['Strandin, Tomas', 'Hepojoki, Jussi', 'Wang, Hao', 'Vaheri, Antti', 'Lankinen, Hilkka']",Virol J,,,True
357f5b1caf114fdb8a60870473af88bc9017bf14,PMC,Factors influencing psychological distress during a disease epidemic: Data from Australia's first outbreak of equine influenza,http://dx.doi.org/10.1186/1471-2458-8-347,PMC2571100,18831770,CC BY,"BACKGROUND: In 2007 Australia experienced its first outbreak of highly infectious equine influenza. Government disease control measures were put in place to control, contain, and eradicate the disease; these measures included movement restrictions and quarantining of properties. This study was conducted to assess the psycho-social impacts of this disease, and this paper reports the prevalence of, and factors influencing, psychological distress during this outbreak. METHODS: Data were collected using an online survey, with a link directed to the affected population via a number of industry groups. Psychological distress, as determined by the Kessler 10 Psychological Distress Scale, was the main outcome measure. RESULTS: In total, 2760 people participated in this study. Extremely high levels of non-specific psychological distress were reported by respondents in this study, with 34% reporting high psychological distress (K10 > 22), compared to levels of around 12% in the Australian general population. Analysis, using backward stepwise binary logistic regression analysis, revealed that those living in high risk infection (red) zones (OR = 2.00; 95% CI: 1.57–2.55; p < 0.001) and disease buffer (amber) zones (OR = 1.83; 95% CI: 1.36–2.46; p < 0.001) were at much greater risk of high psychological distress than those living in uninfected (white zones). Although prevalence of high psychological distress was greater in infected EI zones and States, elevated levels of psychological distress were experienced in horse-owners nationally. Statistical analysis indicated that certain groups were more vulnerable to high psychological distress; specifically younger people, and those with lower levels of formal educational qualifications. Respondents whose principal source of income was from horse-related industry were more than twice as likely to have high psychological distress than those whose primary source of income was not linked to horse-related industry (OR = 2.23; 95% CI: 1.82–2.73; p < 0.001). CONCLUSION: Although, methodologically, this study had good internal validity, it has limited generalisability because it was not possible to identify, bound, or sample the target population accurately. However, this study is the first to collect psychological distress data from an affected population during such a disease outbreak and has potential to inform those involved in assessing the potential psychological impacts of human infectious diseases, such as pandemic influenza.",2008 Oct 3,"['Taylor, Melanie R', 'Agho, Kingsley E', 'Stevens, Garry J', 'Raphael, Beverley']",BMC Public Health,,,True
ee0d298d09635c5ae72d4584fba105a705d25afb,PMC,Broadening of Neutralization Activity to Directly Block a Dominant Antibody-Driven SARS-Coronavirus Evolution Pathway,http://dx.doi.org/10.1371/journal.ppat.1000197,PMC2572002,18989460,CC0,"Phylogenetic analyses have provided strong evidence that amino acid changes in spike (S) protein of animal and human SARS coronaviruses (SARS-CoVs) during and between two zoonotic transfers (2002/03 and 2003/04) are the result of positive selection. While several studies support that some amino acid changes between animal and human viruses are the result of inter-species adaptation, the role of neutralizing antibodies (nAbs) in driving SARS-CoV evolution, particularly during intra-species transmission, is unknown. A detailed examination of SARS-CoV infected animal and human convalescent sera could provide evidence of nAb pressure which, if found, may lead to strategies to effectively block virus evolution pathways by broadening the activity of nAbs. Here we show, by focusing on a dominant neutralization epitope, that contemporaneous- and cross-strain nAb responses against SARS-CoV spike protein exist during natural infection. In vitro immune pressure on this epitope using 2002/03 strain-specific nAb 80R recapitulated a dominant escape mutation that was present in all 2003/04 animal and human viruses. Strategies to block this nAb escape/naturally occurring evolution pathway by generating broad nAbs (BnAbs) with activity against 80R escape mutants and both 2002/03 and 2003/04 strains were explored. Structure-based amino acid changes in an activation-induced cytidine deaminase (AID) “hot spot” in a light chain CDR (complementarity determining region) alone, introduced through shuffling of naturally occurring non-immune human VL chain repertoire or by targeted mutagenesis, were successful in generating these BnAbs. These results demonstrate that nAb-mediated immune pressure is likely a driving force for positive selection during intra-species transmission of SARS-CoV. Somatic hypermutation (SHM) of a single VL CDR can markedly broaden the activity of a strain-specific nAb. The strategies investigated in this study, in particular the use of structural information in combination of chain-shuffling as well as hot-spot CDR mutagenesis, can be exploited to broaden neutralization activity, to improve anti-viral nAb therapies, and directly manipulate virus evolution.",2008 Nov 7,"['Sui, Jianhua', 'Aird, Daniel R.', 'Tamin, Azaibi', 'Murakami, Akikazu', 'Yan, Meiying', 'Yammanuru, Anuradha', 'Jing, Huaiqi', 'Kan, Biao', 'Liu, Xin', 'Zhu, Quan', 'Yuan, Qing-an', 'Adams, Gregory P.', 'Bellini, William J.', 'Xu, Jianguo', 'Anderson, Larry J.', 'Marasco, Wayne A.']",PLoS Pathog,,,True
7ee508ec11743a3ef6f496edaee487e68ace2368,PMC,Influenza A Virus Inhibits Type I IFN Signaling via NF-κB-Dependent Induction of SOCS-3 Expression,http://dx.doi.org/10.1371/journal.ppat.1000196,PMC2572141,18989459,CC BY,"The type I interferon (IFN) system is a first line of defense against viral infections. Viruses have developed various mechanisms to counteract this response. So far, the interferon antagonistic activity of influenza A viruses was mainly observed on the level of IFNβ gene induction via action of the viral non-structural protein 1 (NS1). Here we present data indicating that influenza A viruses not only suppress IFNβ gene induction but also inhibit type I IFN signaling through a mechanism involving induction of the suppressor of cytokine signaling-3 (SOCS-3) protein. Our study was based on the observation that in cells that were infected with influenza A virus and subsequently stimulated with IFNα/β, phosphorylation of the signal transducer and activator of transcription protein 1 (STAT1) was strongly reduced. This impaired STAT1 activation was not due to the action of viral proteins but rather appeared to be induced by accumulation of viral 5′ triphosphate RNA in the cell. SOCS proteins are potent endogenous inhibitors of Janus kinase (JAK)/STAT signaling. Closer examination revealed that SOCS-3 but not SOCS-1 mRNA levels increase in an RNA- and nuclear factor kappa B (NF-κB)-dependent but type I IFN-independent manner early in the viral replication cycle. This direct viral induction of SOCS-3 mRNA and protein expression appears to be relevant for suppression of the antiviral response since in SOCS-3 deficient cells a sustained phosphorylation of STAT1 correlated with elevated expression of type I IFN-dependent genes. As a consequence, progeny virus titers were reduced in SOCS-3 deficient cells or in cells were SOCS-3 expression was knocked-down by siRNA. These data provide the first evidence that influenza A viruses suppress type I IFN signaling on the level of JAK/STAT activation. The inhibitory effect is at least in part due to the induction of SOCS-3 gene expression, which results in an impaired antiviral response.",2008 Nov 7,"['Pauli, Eva-K.', 'Schmolke, Mirco', 'Wolff, Thorsten', 'Viemann, Dorothee', 'Roth, Johannes', 'Bode, Johannes G.', 'Ludwig, Stephan']",PLoS Pathog,,,True
f2af8027b6801850481d09ad0d4c5eb8e31c7d7f,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,True
b8897cea528329455c8e8844a01a5564f34e0e5b,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
66c71e446eadea81cba685fd60bb998990ae6152,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
ceabefd03cf7f09d8c21c9a4a2a784264a6863ab,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
6bfdcf172d10bb3c2e525e7663c65e68ca46f141,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
d22d9e23166f9616aba549098abb323b755b8e7f,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
6d15a3df85701850bd4ebb87f53ca9067e1a9c28,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
57dde8dc0635466830e49cbe6f637f60d2a5548b,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
558daeea8c79f3d8cdbbe23ac1d56dd3880b483a,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
1dafb500595e1264149df72ffc5376c0ddefab27,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
88967166e15bd6cbe70cfd4a3da2fabf467d774a,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
2e677b4ce2466577ae6c79a61e6b8bda482b24b3,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
c70f403fc3480350ea777cc469e5a726154b6ee3,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
0f20ec4a5e8c127bd73cc8fe068f7b3968109671,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
d2b4782c75bfa05865a5f3191614a20dcd1f38a5,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
ca2a9474b1355a82b175767d68aaba4995e60681,PMC,Seeking Membranes: Positive-Strand RNA Virus Replication Complexes,http://dx.doi.org/10.1371/journal.pbio.0060270,PMC2573941,18959488,CC BY,How much do we really understand about how +RNA viruses usurp and transform the intracellular architecture of host cells when they replicate?,2008 Oct 28,"Denison, Mark R",PLoS Biol,,,True
3ee10f61fbf042f0e6c1f90b5e26a1199c13f177,PMC,Could FIV zoonosis responsible of the breakdown of the pathocenosis which has reduced the European CCR5-Delta32 allele frequencies?,http://dx.doi.org/10.1186/1743-422X-5-119,PMC2575341,18925940,CC BY,"BACKGROUND: In Europe, the north-south downhill cline frequency of the chemokine receptor CCR5 allele with a 32-bp deletion (CCR5-Δ32) raises interesting questions for evolutionary biologists. We had suggested first that, in the past, the European colonizers, principally Romans, might have been instrumental of a progressively decrease of the frequencies southwards. Indeed, statistical analyses suggested strong negative correlations between the allele frequency and historical parameters including the colonization dates by Mediterranean civilisations. The gene flows from colonizers to native populations were extremely low but colonizers are responsible of the spread of several diseases suggesting that the dissemination of parasites in naive populations could have induced a breakdown rupture of the fragile pathocenosis changing the balance among diseases. The new equilibrium state has been reached through a negative selection of the null allele. RESULTS: Most of the human diseases are zoonoses and cat might have been instrumental in the decrease of the allele frequency, because its diffusion through Europe was a gradual process, due principally to Romans; and that several cat zoonoses could be transmitted to man. The possible implication of a feline lentivirus (FIV) which does not use CCR5 as co-receptor is discussed. This virus can infect primate cells in vitro and induces clinical signs in macaque. Moreover, most of the historical regions with null or low frequency of CCR5-Δ32 allele coincide with historical range of the wild felid species which harbor species-specific FIVs. CONCLUSION: We proposed the hypothesis that the actual European CCR5 allelic frequencies are the result of a negative selection due to a disease spreading. A cat zoonosis, could be the most plausible hypothesis. Future studies could provide if CCR5 can play an antimicrobial role in FIV pathogenesis. Moreover, studies of ancient DNA could provide more evidences regarding the implications of zoonoses in the actual CCR5-Δ32 distribution.",2008 Oct 16,"Faure, Eric",Virol J,,,True
9c33102dc55e225f5836f9cf9c9d5f5b918820d8,PMC,Key Role of Splenic Myeloid DCs in the IFN-αβ Response to Adenoviruses In Vivo,http://dx.doi.org/10.1371/journal.ppat.1000208,PMC2576454,19008951,CC BY,"The early systemic production of interferon (IFN)-αβ is an essential component of the antiviral host defense mechanisms, but is also thought to contribute to the toxic side effects accompanying gene therapy with adenoviral vectors. Here we investigated the IFN-αβ response to human adenoviruses (Ads) in mice. By comparing the responses of normal, myeloid (m)DC- and plasmacytoid (p)DC-depleted mice and by measuring IFN-αβ mRNA expression in different organs and cells types, we show that in vivo, Ads elicit strong and rapid IFN-αβ production, almost exclusively in splenic mDCs. Using knockout mice, various strains of Ads (wild type, mutant and UV-inactivated) and MAP kinase inhibitors, we demonstrate that the Ad-induced IFN-αβ response does not require Toll-like receptors (TLR), known cytosolic sensors of RNA (RIG-I/MDA-5) and DNA (DAI) recognition and interferon regulatory factor (IRF)-3, but is dependent on viral endosomal escape, signaling via the MAP kinase SAPK/JNK and IRF-7. Furthermore, we show that Ads induce IFN-αβ and IL-6 in vivo by distinct pathways and confirm that IFN-αβ positively regulates the IL-6 response. Finally, by measuring TNF-α responses to LPS in Ad-infected wild type and IFN-αβR(−/−) mice, we show that IFN-αβ is the key mediator of Ad-induced hypersensitivity to LPS. These findings indicate that, like endosomal TLR signaling in pDCs, TLR-independent virus recognition in splenic mDCs can also produce a robust early IFN-αβ response, which is responsible for the bulk of IFN-αβ production induced by adenovirus in vivo. The signaling requirements are different from known TLR-dependent or cytosolic IFN-αβ induction mechanisms and suggest a novel cytosolic viral induction pathway. The hypersensitivity to components of the microbial flora and invading pathogens may in part explain the toxic side effects of adenoviral gene therapy and contribute to the pathogenesis of adenoviral disease.",2008 Nov 14,"['Fejer, György', 'Drechsel, Lisa', 'Liese, Jan', 'Schleicher, Ulrike', 'Ruzsics, Zsolt', 'Imelli, Nicola', 'Greber, Urs F.', 'Keck, Simone', 'Hildenbrand, Bernd', 'Krug, Anne', 'Bogdan, Christian', 'Freudenberg, Marina A.']",PLoS Pathog,,,True
312f1e49512a7626113891f7796d4c2c318c7e39,PMC,Genetic immunization with Hantavirus vaccine combining expression of G2 glycoprotein and fused interleukin-2,http://dx.doi.org/10.1186/1479-0556-6-15,PMC2577087,18940009,CC BY,"In this research, we developed a novel chimeric HTNV-IL-2-G2 DNA vaccine plasmid by genetically linking IL-2 gene to the G2 segment DNA and tested whether it could be a candidate vaccine. Chimeric gene was first expressed in eukaryotic expression system pcDNA3.1 (+). The HTNV-IL-2-G2 expressed a 72 kDa fusion protein in COS-7 cells. Meanwhile, the fusion protein kept the activity of its parental proteins. Furthermore, BALB/c mice were vaccinated by the chimeric gene. ELISA, cell microculture neutralization test in vitro were used to detect the humoral immune response in immunized BALB/c mice. Lymphocyte proliferation assay was used to detect the cellular immune response.- The results showed that the chimeric gene could simultaneously evoke specific antibody against G2 glycoprotein and IL-2. And the immunized mice of every group elicited neutralizing antibodies with different titers. Lymphocyte proliferation assay results showed that the stimulation indexes of splenocytes of chimeric gene to G2 and IL-2 were significantly higher than that of other groups. Our results suggest that IL-2-based HTNV G2 DNA can induce both humoral and cellular immune response specific for HTNV G2 and can be a candidate DNA vaccine for HTNV infection.",2008 Oct 22,"['Hao, Huang', 'Xiu, Li', 'Zehua, Zhang', 'Min, Jia', 'Hongbo, Hu', 'Zhihong, Wu', 'Zhenhua, Zhu', 'Xiaohong, Wan', 'Hanju, Huang']",Genet Vaccines Ther,,,True
9f7ed2037968c63fa97eb6fc7c35e9738a654541,PMC,Gender difference in knowledge of tuberculosis and associated health-care seeking behaviors: a cross-sectional study in a rural area of China,http://dx.doi.org/10.1186/1471-2458-8-354,PMC2577657,18842127,CC BY,"BACKGROUND: Tuberculosis (TB) detection under the national TB control program in China follows passive case-finding guidelines, which could be influenced by the accessibility of health service and patient's health-care seeking behaviors. One intriguing topic is the correlation between men and women's knowledge on TB and their health-care seeking behaviors. METHODS: Two cross-sectional studies were separately carried out in Yangzhong County, a rural area of China. One study, by using systematic sampling method, including 1,200 subjects, was conducted to investigate the TB knowledge among general population. Another study in the same source population screened 33,549 people aged 15 years or over among 20 stratified cluster-sampled villages for identifying prolonged cough patients at households and individual interviews were then carried out. Gender difference in the knowledge of TB and health-care seeking behaviors was analyzed particularly. RESULTS: Among general population, only 16.0% (men 17.1% vs. women 15.0%) knew the prolonged cough with the duration of 3 weeks or longer was a symptom for suspicious TB. Fewer women than men knew the local appointed health facility for TB diagnosis and treatment as well as the current free TB service policy. Moreover, women were less likely to learn information about TB and share it with others on their own initiatives. On the contrary, after the onset of the prolonged cough, women (79.2%) were more likely to seek health-care than men (58.6%) did. However, a large part of women preferred to visit the lower level non-hospital health facilities at first such as village clinics and drugstores. CONCLUSION: TB and DOTS program were not well known by rural Chinese. Gender issues should be considered to reduce diagnostic delay of TB and improve both men and women's access to qualified health facility for TB care. Strengthening awareness of TB and improving the accessibility of health-care service is essential in TB control strategy, especially under the current vertical TB control system.",2008 Oct 8,"['Wang, Jianming', 'Fei, Yang', 'Shen, Hongbing', 'Xu, Biao']",BMC Public Health,,,True
de707f97b534ca340482600ed1f008b20d7b1b8e,PMC,Procalcitonin levels in acute exacerbation of COPD admitted in ICU: a prospective cohort study,http://dx.doi.org/10.1186/1471-2334-8-145,PMC2577677,18947382,CC BY,"BACKGROUND: Antibiotics are recommended for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to intensive care units (ICU). Serum procalcitonin (PCT) could be a useful tool for selecting patients with a lower probability of developing bacterial infection, but its measurement has not been investigated in this population. METHODS: We conducted a single center prospective cohort study in consecutive COPD patients admitted to the ICU for AECOPD between September 2005 and September 2006. Sputum samples or tracheal aspirates were tested for the presence of bacteria and viruses. PCT levels were measured at the time of admittance, six hours, and 24 hours using a sensitive immunoassay. RESULTS: Thirty nine AECOPD patients were included, 31 of which (79%) required a ventilator support at admission. The median [25%–75% interquartile range] PCT level, assessed in 35/39 patients, was: 0.096 μg/L [IQR, 0.065 to 0.178] at the time of admission, 0.113 μg/L [IQR, 0.074 to 0.548] at six hours, and 0.137 μg/L [IQR, 0.088 to 0.252] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 μg/L in 14/35 (40%) patients and more than 0.25 μg/L in 10/35 (29%) patients, suggesting low and high probability of bacterial infection, respectively. Five species of bacteria and nine species of viruses were detected in 12/39 (31%) patients. Among the four patients positive for Pseudomonas aeruginosa, one had a PCTmax less than 0.25 μg/L and three had a PCTmax less than 0.1 μg/L. The one patient positive for Haemophilus influenzae had a PCTmax more than 0.25 μg/L. The presence or absence of viruses did not influence PCT at time of admission (0.068 vs 0.098 μg/L respectively, P = 0.80). CONCLUSION: The likelihood of bacterial infection is low among COPD patients admitted to ICU for AECOPD (40% with PCT < 0.1 μg/L) suggesting a possible inappropriate use of antibiotics. Further studies are necessary to assess the impact of a procalcitonin-based therapeutic strategy in critically ill COPD patients.",2008 Oct 23,"['Daubin, Cédric', 'Parienti, Jean-Jacques', 'Vabret, Astrid', 'Ramakers, Michel', 'Fradin, Sabine', 'Terzi, Nicolas', 'Freymuth, François', 'Charbonneau, Pierre', 'du Cheyron, Damien']",BMC Infect Dis,,,True
1ff38c46bce64adb553080443f72ff90e61dcbc3,PMC,Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates,http://dx.doi.org/10.1371/journal.ppat.1000225,PMC2582959,19043556,CC0,"Ebola virus (EBOV) is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV) is particularly robust, as it can also confer protection when administered as a postexposure treatment. A concern that has been raised regarding the replication-competent VSV vectors that express EBOV glycoproteins is how these vectors would be tolerated by individuals with altered or compromised immune systems such as patients infected with HIV. This is especially important as all EBOV outbreaks to date have occurred in areas of Central and Western Africa with high HIV incidence rates in the population. In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVΔG/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). All six animals showed no evidence of illness associated with the VSVΔG/ZEBOVGP vaccine, suggesting that this vaccine may be safe in immunocompromised populations. While one goal of the study was to evaluate the safety of the candidate vaccine platform, it was also of interest to determine if altered immune status would affect vaccine efficacy. The vaccine protected 4 of 6 SHIV-infected macaques from death following ZEBOV challenge. Evaluation of CD4+ T cells in all animals showed that the animals that succumbed to lethal ZEBOV challenge had the lowest CD4+ counts, suggesting that CD4+ T cells may play a role in mediating protection against ZEBOV.",2008 Nov 28,"['Geisbert, Thomas W.', 'Daddario-DiCaprio, Kathleen M.', 'Lewis, Mark G.', 'Geisbert, Joan B.', 'Grolla, Allen', 'Leung, Anders', 'Paragas, Jason', 'Matthias, Lennox', 'Smith, Mark A.', 'Jones, Steven M.', 'Hensley, Lisa E.', 'Feldmann, Heinz', 'Jahrling, Peter B.']",PLoS Pathog,,,True
0ab32c7726deaff1ef10c2ee762c2cb917d92929,PMC,Identification and Characterization of a New Orthoreovirus from Patients with Acute Respiratory Infections,http://dx.doi.org/10.1371/journal.pone.0003803,PMC2583042,19030226,CC BY,"First discovered in the early 1950s, reoviruses (respiratory enteric orphan viruses) were not associated with any known disease, and hence named orphan viruses. Recently, our group reported the isolation of the Melaka virus from a patient with acute respiratory disease and provided data suggesting that this new orthoreovirus is capable of human-to-human transmission and is probably of bat origin. Here we report yet another Melaka-like reovirus (named Kampar virus) isolated from the throat swab of a 54 year old male patient in Kampar, Perak, Malaysia who was suffering from high fever, acute respiratory disease and vomiting at the time of virus isolation. Serological studies indicated that Kampar virus was transmitted from the index case to at least one other individual and caused respiratory disease in the contact case. Sequence analysis of the four small class genome segments indicated that Kampar and Melaka viruses are closely related. This was confirmed by virus neutralization assay, showing an effective two-way cross neutralization, i.e., the serum against one virus was able to neutralize the other. Although the exact origin of Kampar virus is unknown, epidemiological tracing revealed that the house of the index case is surrounded by fruit trees frequently visited by fruit bats. There is a high probability that Kampar virus originated from bats and was transmitted to humans via bat droppings or contaminated fruits. The discovery of Kampar virus highlights the increasing trend of emergence of bat zoonotic viruses and the need to expand our understanding of bats as a source of many unknown viruses.",2008 Nov 25,"['Chua, Kaw Bing', 'Voon, Kenny', 'Crameri, Gary', 'Tan, Hui Siu', 'Rosli, Juliana', 'McEachern, Jennifer A.', 'Suluraju, Sivagami', 'Yu, Meng', 'Wang, Lin-Fa']",PLoS One,,,True
727602c6861782ad9eb87bfff3fc6824b7008af5,PMC,Widespread distribution and a new recombinant species of Brazilian virus associated with cotton blue disease,http://dx.doi.org/10.1186/1743-422X-5-123,PMC2583970,18937850,CC BY,"BACKGROUND: Cotton blue disease (CBD), an important global cotton crop pathology responsible for major economic losses, is prevalent in the major cotton-producing states of Brazil. Typical CBD symptoms include stunting due to internodal shortening, leaf rolling, intense green foliage, and yellowing veins. Atypical CBD symptoms, including reddish and withered leaves, were also observed in Brazilian cotton fields in 2007. Recently, a Polerovirus named Cotton leafroll dwarf virus (CLRDV) was shown to be associated with CBD. RESULTS: To understand the distribution and genetic diversity of CLRDV in Brazil, we analyzed 23 CBD-symptomatic plants from susceptible cotton varieties originating from five of the six most important cotton-growing states, from 2004–2007. Here, we report on CLRDV diversity in plants with typical or atypical CBD symptoms by comparing viral coat protein, RNA polymerase (RdRp), and intergenic region genomic sequences. CONCLUSION: The virus had a widespread distribution with a low genetic diversity; however, three divergent isolates were associated with atypical CBD symptoms. These divergent isolates had a CLRDV-related coat protein but a distinct RdRp sequence, and probably arose from recombination events. Based on the taxonomic rules for the family Luteoviridae, we propose that these three isolates represent isolates of a new species in the genus Polerovirus.",2008 Oct 20,"['Silva, TF', 'Corrêa, RL', 'Castilho, Y', 'Silvie, P', 'Bélot, J-L', 'Vaslin, MFS']",Virol J,,,True
36885622f4e863ce69c521612093f1682fed1a5d,PMC,The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile,http://dx.doi.org/10.1186/1755-8794-1-54,PMC2584050,18950519,CC BY,"BACKGROUND: Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints. METHODS: Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides) was used for validation. RESULTS: By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (p < 0.01). Multimarker clustering showed two distinctive proteomic profiles independent of age and ethnicity. Eighteen of 19 cancer samples clustered together (sensitivity 95%) while 27/36 of non-cancer samples clustered in a second group. Nine non-cancer samples that clustered with cancer samples included 5 pre-malignant lesions (1 adenomatous polyp and 4 intestinal metaplasia). Validation using a second sample set showed the sensitivity and specificity to be 88% and 93%, respectively. Positive predictive value of the combined data was 0.80. Selected peptide sequencing identified pepsinogen C and pepsin A activation peptide as significantly down-regulated and alpha-defensin as significantly up-regulated. CONCLUSION: This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.",2008 Oct 25,"['Kon, Oi Lian', 'Yip, Tai-Tung', 'Ho, Meng Fatt', 'Chan, Weng Hoong', 'Wong, Wai Keong', 'Tan, Soo Yong', 'Ng, Wai Har', 'Kam, Siok Yuen', 'Eng, Alvin KH', 'Ho, Patrick', 'Viner, Rosa', 'Ong, Hock Soo', 'Kumarasinghe, M Priyanthi']",BMC Med Genomics,,,True
1a5bdcd1c259d4b40800f9e96219641aafd5f6b9,PMC,Type I feline coronavirus spike glycoprotein fails to recognize aminopeptidase N as a functional receptor on feline cell lines,http://dx.doi.org/10.1099/vir.0.82666-0,PMC2584236,17485536,CC BY,"There are two types of feline coronaviruses that can be distinguished by serology and sequence analysis. Type I viruses, which are prevalent in the field but are difficult to isolate and propagate in cell culture, and type II viruses, which are less prevalent but replicate well in cell culture. An important determinant of coronavirus infection, in vivo and in cell culture, is the interaction of the virus surface glycoprotein with a cellular receptor. It is generally accepted that feline aminopeptidase N can act as a receptor for the attachment and entry of type II strains, and it has been proposed that the same molecule acts as a receptor for type I viruses. However, the experimental data are inconclusive. The aim of the studies reported here was to provide evidence for or against the involvement of feline aminopeptidase N as a receptor for type I feline coronaviruses. Our approach was to produce retroviral pseudotypes that bear the type I or type II feline coronavirus surface glycoprotein and to screen a range of feline cell lines for the expression of a functional receptor for attachment and entry. Our results show that type I feline coronavirus surface glycoprotein fails to recognize feline aminopeptidase N as a functional receptor on three continuous feline cell lines. This suggests that feline aminopeptidase N is not a receptor for type I feline coronaviruses. Our results also indicate that it should be possible to use retroviral pseudotypes to identify and characterize the cellular receptor for type I feline coronaviruses.",2007 Jun,"['Dye, Charlotte', 'Temperton, Nigel', 'Siddell, Stuart G.']",J Gen Virol,,,True
8e9e154ec04f065cca2b000ebc1e86239ef11c54,PMC,Type I feline coronavirus spike glycoprotein fails to recognize aminopeptidase N as a functional receptor on feline cell lines,http://dx.doi.org/10.1099/vir.0.82666-0,PMC2584236,17485536,CC BY,"There are two types of feline coronaviruses that can be distinguished by serology and sequence analysis. Type I viruses, which are prevalent in the field but are difficult to isolate and propagate in cell culture, and type II viruses, which are less prevalent but replicate well in cell culture. An important determinant of coronavirus infection, in vivo and in cell culture, is the interaction of the virus surface glycoprotein with a cellular receptor. It is generally accepted that feline aminopeptidase N can act as a receptor for the attachment and entry of type II strains, and it has been proposed that the same molecule acts as a receptor for type I viruses. However, the experimental data are inconclusive. The aim of the studies reported here was to provide evidence for or against the involvement of feline aminopeptidase N as a receptor for type I feline coronaviruses. Our approach was to produce retroviral pseudotypes that bear the type I or type II feline coronavirus surface glycoprotein and to screen a range of feline cell lines for the expression of a functional receptor for attachment and entry. Our results show that type I feline coronavirus surface glycoprotein fails to recognize feline aminopeptidase N as a functional receptor on three continuous feline cell lines. This suggests that feline aminopeptidase N is not a receptor for type I feline coronaviruses. Our results also indicate that it should be possible to use retroviral pseudotypes to identify and characterize the cellular receptor for type I feline coronaviruses.",2007 Jun,"['Dye, Charlotte', 'Temperton, Nigel', 'Siddell, Stuart G.']",J Gen Virol,,,False
0d80c3f53b8900bb8d958492553dc052c2b3c628,PMC,The role of interleukin-12 in the heavy metal-elicited immunomodulation: relevance of various evaluation methods,http://dx.doi.org/10.1186/1745-6673-3-25,PMC2585571,18990205,CC BY,"BACKGROUND: Increasing evidence exists that heavy metals modulate T helper cell (Th) responses and thereby elicit various pathological manifestation. Interleukin (IL)-12, a crucial innate cytokine, was found to be regulated by such xenobiotic agents. This study aimed at testing whether IL-12 profiles may be indicative of heavy metals-induced immunomodulation. METHODS: Human immunocompetent cells, activated either by monoclonal antibodies or heat-killed Salmonella enterica, were cultured in the absence or presence of cadmium (Cd) acetate or mercuric (Hg) chloride. In vivo experiments were set up where BALB/c mice were exposed to sub-lethal doses of Cd or Hg salts for 3 or 5 weeks. Cytotoxicity was assessed by MTT-reduction assay. Modulation of cytokine profiles was evaluated by enzyme-linked immunosorbent assay (ELISA), cytometric bead-based array (CBA) and real-time polymerase chain reaction (RT-PCR); the relevance of these methods of cytokine quantification was explored. RESULTS: Modulation of IL-12 profiles in Cd- or Hg-exposed human PBMC was dose-dependent and significantly related to IFN-γ levels as well as to the Th1- or Th2-polarized responses. Similarly, skewing the Th1/Th2 ratios in vivo correlated significantly with up- or down-regulation of IL-12 levels in both cases of investigated metals. CONCLUSION: It can be inferred that: (i) IL-12 profiles alone may represent a relevant indicator of heavy metal-induced immune modulation; (ii) evaluating cytokine profiles by CBA is relevant and can adequately replace other methods such as ELISA and RT-PCR in basic research as well as in immune diagnostics; and (iii) targeting IL-12 in therapeutic approaches may be promising to modify Th1/Th2-associated immune disorders.",2008 Nov 6,"Hemdan, Nasr YA",J Occup Med Toxicol,,,True
eec9198400dee7d7ec27088377bced55c01a126a,PMC,Immune Mechanisms Responsible for Vaccination against and Clearance of Mucosal and Lymphatic Norovirus Infection,http://dx.doi.org/10.1371/journal.ppat.1000236,PMC2587711,19079577,CC BY,"Two cardinal manifestations of viral immunity are efficient clearance of acute infection and the capacity to vaccinate against secondary viral exposure. For noroviruses, the contributions of T cells to viral clearance and vaccination have not been elucidated. We report here that both CD4 and CD8 T cells are required for efficient clearance of primary murine norovirus (MNV) infection from the intestine and intestinal lymph nodes. Further, long-lasting protective immunity was generated by oral live virus vaccination. Systemic vaccination with the MNV capsid protein also effectively protected against mucosal challenge, while vaccination with the capsid protein of the distantly related human Lordsdale virus provided partial protection. Fully effective vaccination required a broad immune response including CD4 T cells, CD8 T cells, and B cells, but the importance of specific immune cell types varied between the intestine and intestinal lymph nodes. Perforin, but not interferon gamma, was required for clearance of MNV infection by adoptively transferred T lymphocytes from vaccinated hosts. These studies prove the feasibility of both mucosal and systemic vaccination against mucosal norovirus infection, demonstrate tissue specificity of norovirus immune cells, and indicate that efficient vaccination strategies should induce potent CD4 and CD8 T cell responses.",2008 Dec 12,"['Chachu, Karen A.', 'LoBue, Anna D.', 'Strong, David W.', 'Baric, Ralph S.', 'Virgin, Herbert W.']",PLoS Pathog,,,True
6825e9b1b3377b18ec3725a954b15d2760603a28,PMC,MyD88 Is Required for Protection from Lethal Infection with a Mouse-Adapted SARS-CoV,http://dx.doi.org/10.1371/journal.ppat.1000240,PMC2587915,19079579,CC BY,"A novel human coronavirus, SARS-CoV, emerged suddenly in 2003, causing approximately 8000 human cases and more than 700 deaths worldwide. Since most animal models fail to faithfully recapitulate the clinical course of SARS-CoV in humans, the virus and host factors that mediate disease pathogenesis remain unclear. Recently, our laboratory and others developed a recombinant mouse-adapted SARS-CoV (rMA15) that was lethal in BALB/c mice. In contrast, intranasal infection of young 10-week-old C57BL/6 mice with rMA15 results in a nonlethal infection characterized by high titer replication within the lungs, lung inflammation, destruction of lung tissue, and loss of body weight, thus providing a useful model to identify host mediators of protection. Here, we report that mice deficient in MyD88 (MyD88(−/−)), an adapter protein that mediates Toll-like receptor (TLR), IL-1R, and IL-18R signaling, are far more susceptible to rMA15 infection. The genetic absence of MyD88 resulted in enhanced pulmonary pathology and greater than 90% mortality by day 6 post-infection. MyD88(−/−) mice had significantly higher viral loads in lung tissue throughout the course of infection. Despite increased viral loads, the expression of multiple proinflammatory cytokines and chemokines within lung tissue and recruitment of inflammatory monocytes/macrophages to the lung was severely impaired in MyD88(−/−) mice compared to wild-type mice. Furthermore, mice deficient in chemokine receptors that contribute to monocyte recruitment to the lung were more susceptible to rMA15-induced disease and exhibited severe lung pathology similar to that seen in MyD88(−/−)mice. These data suggest that MyD88-mediated innate immune signaling and inflammatory cell recruitment to the lung are required for protection from lethal rMA15 infection.",2008 Dec 12,"['Sheahan, Timothy', 'Morrison, Thomas E.', 'Funkhouser, William', 'Uematsu, Satoshi', 'Akira, Shizou', 'Baric, Ralph S.', 'Heise, Mark T.']",PLoS Pathog,,,True
fbcfed5be85b5356dd0d103c8b6ab37296035cf5,PMC,Avian Influenza: a global threat needing a global solution,http://dx.doi.org/10.1186/1447-056X-7-5,PMC2588555,19014538,CC BY,"There have been three influenza pandemics since the 1900s, of which the 1919–1919 flu pandemic had the highest mortality rates. The influenza virus infects both humans and birds, and mutates using two mechanisms: antigenic drift and antigenic shift. Currently, the H5N1 avian flu virus is limited to outbreaks among poultry and persons in direct contact to infected poultry, but the mortality rate among infected humans is high. Avian influenza (AI) is endemic in Asia as a result of unregulated poultry rearing in rural areas. Such birds often live in close proximity to humans and this increases the chance of genetic re-assortment between avian and human influenza viruses which may produce a mutant strain that is easily transmitted between humans. Once this happens, a global pandemic is likely. Unlike SARS, a person with influenza infection is contagious before the onset of case-defining symptoms which limits the effectiveness of case isolation as a control strategy. Researchers have shown that carefully orchestrated of public health measures could potentially limit the spread of an AI pandemic if implemented soon after the first cases appear. To successfully contain and control an AI pandemic, both national and global strategies are needed. National strategies include source surveillance and control, adequate stockpiles of anti-viral agents, timely production of flu vaccines and healthcare system readiness. Global strategies such as early integrated response, curbing the disease outbreak at source, utilization of global resources, continuing research and open communication are also critical.",2008 Nov 13,"['Koh, GCH', 'Wong, TY', 'Cheong, SK', 'Koh, DSQ']",Asia Pac Fam Med,,,True
635bc39e204a9e098961ccaef51d67e83226b07e,PMC,"Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection",http://dx.doi.org/10.1186/1742-2094-5-48,PMC2588578,18947414,CC BY,"BACKGROUND: Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. METHODS: To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied. RESULTS: Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap), effects on host cell protein processing (ubiquitin ligase), synapse remodeling (Complement 1q), and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection) and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease). Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of Sylvius and hippocampus, CD4+ and CD8+ T cells, and activated microglia in perivascular areas and brain parenchyma. Genetically resistant, chronically infected mice had substantially less inflammation. CONCLUSION: In outbred mice, chronic, adult acquired T. gondii infection causes neurologic and behavioral abnormalities secondary to inflammation and loss of brain parenchyma. Perivascular inflammation is prominent particularly contiguous to the aqueduct of Sylvius and hippocampus. Even resistant mice have perivascular inflammation. This mouse model of chronic T. gondii infection raises questions of whether persistence of this parasite in brain can cause inflammation or neurodegeneration in genetically susceptible hosts.",2008 Oct 23,"['Hermes, Gretchen', 'Ajioka, James W', 'Kelly, Krystyna A', 'Mui, Ernest', 'Roberts, Fiona', 'Kasza, Kristen', 'Mayr, Thomas', 'Kirisits, Michael J', 'Wollmann, Robert', 'Ferguson, David JP', 'Roberts, Craig W', 'Hwang, Jong-Hee', 'Trendler, Toria', 'Kennan, Richard P', 'Suzuki, Yasuhiro', 'Reardon, Catherine', 'Hickey, William F', 'Chen, Lieping', 'McLeod, Rima']",J Neuroinflammation,,,True
26670350d15f4a1f0a7072ad985d98b21c28fd5a,PMC,Self-Interest versus Group-Interest in Antiviral Control,http://dx.doi.org/10.1371/journal.pone.0001558,PMC2592701,19050769,CC BY,"Antiviral agents have been hailed to hold considerable promise for the treatment and prevention of emerging viral diseases like H5N1 avian influenza and SARS. However, antiviral drugs are not completely harmless, and the conditions under which individuals are willing to participate in a large-scale antiviral drug treatment program are as yet unknown. We provide population dynamical and game theoretical analyses of large-scale prophylactic antiviral treatment programs. Throughout we compare the antiviral control strategy that is optimal from the public health perspective with the control strategy that would evolve if individuals make their own, rational decisions. To this end we investigate the conditions under which a large-scale antiviral control program can prevent an epidemic, and we analyze at what point in an unfolding epidemic the risk of infection starts to outweigh the cost of antiviral treatment. This enables investigation of how the optimal control strategy is moulded by the efficacy of antiviral drugs, the risk of mortality by antiviral prophylaxis, and the transmissibility of the pathogen. Our analyses show that there can be a strong incentive for an individual to take less antiviral drugs than is optimal from the public health perspective. In particular, when public health asks for early and aggressive control to prevent or curb an emerging pathogen, for the individual antiviral drug treatment is attractive only when the risk of infection has become non-negligible. It is even possible that from a public health perspective a situation in which everybody takes antiviral drugs is optimal, while the process of individual choice leads to a situation where nobody is willing to take antiviral drugs.",2008 Feb 13,"['van Boven, Michiel', 'Klinkenberg, Don', 'Pen, Ido', 'Weissing, Franz J.', 'Heesterbeek, Hans']",PLoS One,,,True
6a8a9b70b5eac41b7aebe94c6ed55930696aac59,PMC,Self-Interest versus Group-Interest in Antiviral Control,http://dx.doi.org/10.1371/journal.pone.0001558,PMC2592701,19050769,CC BY,"Antiviral agents have been hailed to hold considerable promise for the treatment and prevention of emerging viral diseases like H5N1 avian influenza and SARS. However, antiviral drugs are not completely harmless, and the conditions under which individuals are willing to participate in a large-scale antiviral drug treatment program are as yet unknown. We provide population dynamical and game theoretical analyses of large-scale prophylactic antiviral treatment programs. Throughout we compare the antiviral control strategy that is optimal from the public health perspective with the control strategy that would evolve if individuals make their own, rational decisions. To this end we investigate the conditions under which a large-scale antiviral control program can prevent an epidemic, and we analyze at what point in an unfolding epidemic the risk of infection starts to outweigh the cost of antiviral treatment. This enables investigation of how the optimal control strategy is moulded by the efficacy of antiviral drugs, the risk of mortality by antiviral prophylaxis, and the transmissibility of the pathogen. Our analyses show that there can be a strong incentive for an individual to take less antiviral drugs than is optimal from the public health perspective. In particular, when public health asks for early and aggressive control to prevent or curb an emerging pathogen, for the individual antiviral drug treatment is attractive only when the risk of infection has become non-negligible. It is even possible that from a public health perspective a situation in which everybody takes antiviral drugs is optimal, while the process of individual choice leads to a situation where nobody is willing to take antiviral drugs.",2008 Feb 13,"['van Boven, Michiel', 'Klinkenberg, Don', 'Pen, Ido', 'Weissing, Franz J.', 'Heesterbeek, Hans']",PLoS One,,,False
6783ff6a7398428f7a6bb894d39c44746b85cf73,PMC,A quality assessment of genetic association studies supporting susceptibility and outcome in acute lung injury,http://dx.doi.org/10.1186/cc7098,PMC2592769,18950526,CC BY,"INTRODUCTION: Clinical observations and animal models provide evidence that the development of acute lung injury (ALI), a phenomenon of acute diffuse lung inflammation in critically ill patients, is influenced by genetic factors. Association studies are the main tool for exploring common genetic variations underlying ALI susceptibility and/or outcome. We aimed to assess the quality of positive genetic association studies with ALI susceptibility and/or outcome in adults in order to highlight their consistency and major limitations. METHODS: We conducted a broad PubMed literature search from 1996 to June 2008 for original articles in English supporting a positive association (P ≤ 0.05) of genetic variants contributing to all-cause ALI susceptibility and/or outcome. Studies were evaluated based on current recommendations using a 10-point quality scoring system derived from 14 criteria, and the gene was considered as the unit of replication. Genes were also categorized according to biological processes using the Gene Ontology. RESULTS: Our search identified a total of 29 studies reporting positive findings for 16 genes involved mainly in the response to external stimulus and cell signal transduction. The genes encoding for interleukin-6, mannose-binding lectin, surfactant protein B, and angiotensin-converting enzyme were the most replicated across the studies. On average, the studies had an intermediate quality score (median of 4.62 and interquartile range of 3.33 to 6.15). CONCLUSIONS: Although the quality of association studies seems to have improved over the years, more and better designed studies, including the replication of previous findings, with larger sample sizes extended to population groups other than those of European descent, are needed for identifying firm genetic modifiers of ALI.",2008 Oct 25,"['Flores, Carlos', 'del Mar Pino-Yanes, Maria', 'Villar, Jesús']",Crit Care,,,True
25e0a5092935b57609da913715f5e1e5e6ecb91f,PMC,Plaque assay for human coronavirus NL63 using human colon carcinoma cells,http://dx.doi.org/10.1186/1743-422X-5-138,PMC2603006,19014487,CC BY,"BACKGROUND: Coronaviruses cause a broad range of diseases in animals and humans. Human coronavirus (hCoV) NL63 is associated with up to 10% of common colds. Viral plaque assays enable the characterization of virus infectivity and allow for purifying virus stock solutions. They are essential for drug screening. Hitherto used cell cultures for hCoV-NL63 show low levels of virus replication and weak and diffuse cytopathogenic effects. It has not yet been possible to establish practicable plaque assays for this important human pathogen. RESULTS: 12 different cell cultures were tested for susceptibility to hCoV-NL63 infection. Human colon carcinoma cells (CaCo-2) replicated virus more than 100 fold more efficiently than commonly used African green monkey kidney cells (LLC-MK2). CaCo-2 cells showed cytopathogenic effects 4 days post infection. Avicel, agarose and carboxymethyl-cellulose overlays proved suitable for plaque assays. Best results were achieved with Avicel, which produced large and clear plaques from the 4(th )day of infection. The utility of plaque assays with agrose overlay was demonstrated for purifying virus, thereby increasing viral infectivity by 1 log 10 PFU/mL. CONCLUSION: CaCo-2 cells support hCoV-NL63 better than LLC-MK2 cells and enable cytopathogenic plaque assays. Avicel overlay is favourable for plaque quantification, and agarose overlay is preferred for plaque purification. HCoV-NL63 virus stock of increased infectivity will be beneficial in antiviral screening, animal modelling of disease, and other experimental tasks.",2008 Nov 12,"['Herzog, Petra', 'Drosten, Christian', 'Müller, Marcel A']",Virol J,,,True
b41f3634a764bf08cbc4588f37d7d422a02fa541,PMC,Development and evaluation of a leadership training program for public health emergency response: results from a Chinese study,http://dx.doi.org/10.1186/1471-2458-8-377,PMC2605461,18973664,CC BY,"BACKGROUND: Since the 9/11 attack and severe acute respiratory syndrome (SARS), the development of qualified and able public health leaders has become a new urgency in building the infrastructure needed to address public health emergencies. Although previous studies have reported that the training of individual leaders is an important approach, the systemic and scientific training model need further improvement and development. The purpose of this study was to develop, deliver, and evaluate a participatory leadership training program for emergency response. METHODS: Forty-one public health leaders (N = 41) from five provinces completed the entire emergency preparedness training program in China. The program was evaluated by anonymous questionnaires and semi-structured interviews held prior to training, immediately post-training and 12-month after training (Follow-up). RESULTS: The emergency preparedness training resulted in positive shifts in knowledge, self-assessment of skills for public health leaders. More than ninety-five percent of participants reported that the training model was scientific and feasible. Moreover, the response of participants in the program to the avian influenza outbreak, as well as the planned evaluations for this leadership training program, further demonstrated both the successful approaches and methods and the positive impact of this integrated leadership training initiative. CONCLUSION: The emergency preparedness training program met its aims and objectives satisfactorily, and improved the emergency capability of public health leaders. This suggests that the leadership training model was effective and feasible in improving the emergency preparedness capability.",2008 Oct 30,"['Wang, Chongjian', 'Wei, Sheng', 'Xiang, Hao', 'Wu, Jing', 'Xu, Yihua', 'Liu, Li', 'Nie, Shaofa']",BMC Public Health,,,True
0a41b85153ef8a084f7b3476d4d38832f533e914,PMC,Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference,http://dx.doi.org/10.1371/journal.pone.0004118,PMC2606062,19122813,CC BY,"BACKGROUND: Equine herpesvirus type 1 (EHV-1), a member of the Alphaherpesvirinae, is spread via nasal secretions and causes respiratory disease, neurological disorders and abortions. The virus is a significant equine pathogen, but current EHV-1 vaccines are only partially protective and effective metaphylactic and therapeutic agents are not available. Small interfering RNAs (siRNA's), delivered intranasally, could prove a valuable alternative for infection control. siRNA's against two essential EHV-1 genes, encoding the viral helicase (Ori) and glycoprotein B, were evaluated for their potential to decrease EHV-1 infection in a mouse model. METHODOLOGY/PRINCIPAL FNDINGS: siRNA therapy in vitro significantly reduced virus production and plaque size. Viral titers were reduced 80-fold with 37.5 pmol of a single siRNA or with as little as 6.25 pmol of each siRNA when used in combination. siRNA therapy in vivo significantly reduced viral replication and clinical signs. Intranasal treatment did not require a transport vehicle and proved effective when given up to 12 h before or after infection. CONCLUSIONS/SIGNIFICANCE: siRNA treatment has potential for both prevention and early treatment of EHV-1 infections.",2009 Jan 5,"['Fulton, Amy', 'Peters, Sarah T.', 'Perkins, Gillian A.', 'Jarosinski, Keith W.', 'Damiani, Armando', 'Brosnahan, Margaret', 'Buckles, Elizabeth L.', 'Osterrieder, Nikolaus', 'Van de Walle, Gerlinde R.']",PLoS One,,,True
9693080ead2c95fe79e8bf077637b5585cac664f,PMC,Resequencing microarray probe design for typing genetically diverse viruses: human rhinoviruses and enteroviruses,http://dx.doi.org/10.1186/1471-2164-9-577,PMC2607299,19046445,CC BY,"BACKGROUND: Febrile respiratory illness (FRI) has a high impact on public health and global economics and poses a difficult challenge for differential diagnosis. A particular issue is the detection of genetically diverse pathogens, i.e. human rhinoviruses (HRV) and enteroviruses (HEV) which are frequent causes of FRI. Resequencing Pathogen Microarray technology has demonstrated potential for differential diagnosis of several respiratory pathogens simultaneously, but a high confidence design method to select probes for genetically diverse viruses is lacking. RESULTS: Using HRV and HEV as test cases, we assess a general design strategy for detecting and serotyping genetically diverse viruses. A minimal number of probe sequences (26 for HRV and 13 for HEV), which were potentially capable of detecting all serotypes of HRV and HEV, were determined and implemented on the Resequencing Pathogen Microarray RPM-Flu v.30/31 (Tessarae RPM-Flu). The specificities of designed probes were validated using 34 HRV and 28 HEV strains. All strains were successfully detected and identified at least to species level. 33 HRV strains and 16 HEV strains could be further differentiated to serotype level. CONCLUSION: This study provides a fundamental evaluation of simultaneous detection and differential identification of genetically diverse RNA viruses with a minimal number of prototype sequences. The results demonstrated that the newly designed RPM-Flu v.30/31 can provide comprehensive and specific analysis of HRV and HEV samples which implicates that this design strategy will be applicable for other genetically diverse viruses.",2008 Dec 1,"['Wang, Zheng', 'Malanoski, Anthony P', 'Lin, Baochuan', 'Kidd, Carolyn', 'Long, Nina C', 'Blaney, Kate M', 'Thach, Dzung C', 'Tibbetts, Clark', 'Stenger, David A']",BMC Genomics,,,True
e63eaf2a9904a7212185d87824ddd187ab110272,PMC,The expression and antigenicity of a truncated spike-nucleocapsid fusion protein of severe acute respiratory syndrome-associated coronavirus,http://dx.doi.org/10.1186/1471-2180-8-207,PMC2613400,19038059,CC BY,"BACKGROUND: In the absence of effective drugs, controlling SARS relies on the rapid identification of cases and appropriate management of the close contacts, or effective vaccines for SARS. Therefore, developing specific and sensitive laboratory tests for SARS as well as effective vaccines are necessary for national authorities. RESULTS: Genes encoding truncated nucleocapsid (N) and spike (S) proteins of SARSCoV were cloned into the expression vector pQE30 and fusionally expressed in Escherichia coli M15. The fusion protein was analyzed for reactivity with SARS patients' sera and with anti-sera against the two human coronaviruses HCoV 229E and HCoV OC43 by ELISA, IFA and immunoblot assays. Furthermore, to evaluate the antigen-specific humoral antibody and T-cell responses in mice, the fusion protein was injected into 6-week-old BALB/c mice and a neutralization test as well as a T-cell analysis was performed. To evaluate the antiviral efficacy of immunization, BALB/c mice were challenged intranasally with SARSCoV at day 33 post injection and viral loads were determined by fluorescent quantitative RT-PCR. Serological results showed that the diagnostic sensitivity and specificity of the truncated S-N fusion protein derived the SARS virus were > 99% (457/460) and 100.00% (650/650), respectively. Furthermore there was no cross-reactivity with other two human coronaviruses. High titers of antibodies to SRASCoV appeared in the immunized mice and the neutralization test showed that antibodies to the fusion protein could inhibit SARSCoV. The T cell proliferation showed that the fusion protein could induce an antigen-specific T-cell response. Fluorescent quantitative RT-PCR showed that BALB/c mice challenged intranasally with SARSCoV at day 33 post injection were completely protected from virus replication. CONCLUSION: The truncated S-N fusion protein is a suitable immunodiagnostic antigen and vaccine candidate.",2008 Nov 28,"['Mu, Feng', 'Niu, Dongsheng', 'Mu, Jingsong', 'He, Bo', 'Han, Weiguo', 'Fan, Baoxing', 'Huang, Shengyong', 'Qiu, Yan', 'You, Bo', 'Chen, Weijun']",BMC Microbiol,,,True
c4fc28f1a66e4664a3dc12f5b121ee97aa9f122d,PMC,A Novel Replication-Competent Vaccinia Vector MVTT Is Superior to MVA for Inducing High Levels of Neutralizing Antibody via Mucosal Vaccination,http://dx.doi.org/10.1371/journal.pone.0004180,PMC2613559,19159014,CC BY,"Mucosal vaccination offers great advantage for inducing protective immune response to prevent viral transmission and dissemination. Here, we report our findings of a head-to-head comparison of two viral vectors modified vaccinia Ankara (MVA) and a novel replication-competent modified vaccinia Tian Tan (MVTT) for inducing neutralizing antibodies (Nabs) via intramuscular and mucosal vaccinations in mice. MVTT is an attenuated variant of the wild-type VTT, which was historically used as a smallpox vaccine for millions of Chinese people. The spike glycoprotein (S) of SARS-CoV was used as the test antigen after the S gene was constructed in the identical genomic location of two vectors to generate vaccine candidates MVTT-S and MVA-S. Using identical doses, MVTT-S induced lower levels (∼2-3-fold) of anti- SARS-CoV neutralizing antibodies (Nabs) than MVA-S through intramuscular inoculation. MVTT-S, however, was capable of inducing consistently 20-to-100-fold higher levels of Nabs than MVA-S when inoculated via either intranasal or intraoral routes. These levels of MVTT-S-induced Nab responses were substantially (∼10-fold) higher than that induced via the intramuscular route in the same experiments. Moreover, pre-exposure to the wild-type VTT via intranasal or intraoral route impaired the Nab response via the same routes of MVTT-S vaccination probably due to the pre-existing anti-VTT Nab response. The efficacy of intranasal or intraoral vaccination, however, was still 20-to-50-fold better than intramuscular inoculation despite the subcutaneous pre-exposure to wild-type VTT. Our data have implications for people who maintain low levels of anti-VTT Nabs after historical smallpox vaccination. MVTT is therefore an attractive live viral vector for mucosal vaccination.",2009 Jan 13,"['Huang, Xiaoxing', 'Lu, Bin', 'Yu, Wenbo', 'Fang, Qing', 'Liu, Li', 'Zhuang, Ke', 'Shen, Tingting', 'Wang, Haibo', 'Tian, Po', 'Zhang, Linqi', 'Chen, Zhiwei']",PLoS One,,,True
eb83b27bafc37b40794c2c7cc1b921cbcdb4138c,PMC,Augmented Lung Inflammation Protects against Influenza A Pneumonia,http://dx.doi.org/10.1371/journal.pone.0004176,PMC2613561,19137067,CC BY,"BACKGROUND: Influenza pneumonia causes high mortality every year, and pandemic episodes kill millions of people. Influenza-related mortality has been variously ascribed to an ineffective host response that fails to limit viral replication, an excessive host inflammatory response that results in lung injury and impairment of gas exchange, or to bacterial superinfection. We sought to determine whether lung inflammation promoted or impaired host survival in influenza pneumonia. METHODS AND FINDINGS: To distinguish among these possible causes of influenza-related death, we induced robust lung inflammation by exposing mice to an aerosolized bacterial lysate prior to challenge with live virus. The treatment induced expression of the inflammatory cytokines IL-6 and TNF in bronchoalveolar lavage fluid 8- and 40-fold greater, respectively, than that caused by lethal influenza infection. Yet, this augmented inflammation was associated with striking resistance to host mortality (0% vs 90% survival, p = 0.0001) and reduced viral titers (p = 0.004). Bacterial superinfection of virus infected lungs was not observed. When mice were repeatedly exposed to the bacterial lysate, as would be clinically desirable during an influenza epidemic, there was no tachyphylaxis of the induced viral resistance. When the bacterial lysate was administered after the viral challenge, there was still some mortality benefit, and when ribavirin was added to the aerosolized bacterial lysate, host survival was synergistically improved (0% vs 93.3% survival, p<0.0001). CONCLUSIONS: Together, these data indicate that innate immune resistance to influenza can be effectively stimulated, and suggest that ineffective rather than excessive inflammation is the major cause of mortality in influenza pneumonia.",2009 Jan 12,"['Tuvim, Michael J.', 'Evans, Scott E.', 'Clement, Cecilia G.', 'Dickey, Burton F.', 'Gilbert, Brian E.']",PLoS One,,,True
b5f778aafd8e2a94701f7398641519a2041ab303,PMC,The impact of SARS on hospital performance,http://dx.doi.org/10.1186/1472-6963-8-228,PMC2613902,18990210,CC BY,"BACKGROUND: During the SARS epidemic, healthcare utilization and medical services decreased significantly. However, the long-term impact of SARS on hospital performance needs to be further discussed. METHODS: A municipal hospital in Taipei City was shut down for a month due to SARS and then became the designated SARS and infectious disease hospital for the city. This study collected the outpatient, inpatient and emergency service volumes for every year from April to March over four years. Average monthly service amount ± standard deviation were used to compare patient volume for the whole hospital, as well as the outpatient numbers accessing different departments. The ARIMA model of outpatient volume in the pre-SARS year was developed. RESULTS: The average monthly service volume of outpatient visits for the base year 2002 was 52317 ± 4204 visits per month, and number for 2003 and the following two years were 55%, 82% and 84% of the base year respectively. The average emergency service volume was 4382 ± 356 visits per month at the base year and this became 45%, 77% and 87% of the base year for the following three years respectively. Average inpatient service volume was 8520 ± 909 inpatient days per month at the base year becoming 43%, 81% and 87% of the base year for the following three years respectively. Only the emergency service volume had recovered to the level of a non-significant difference at the second year after SARS. In addition, the departments of family medicine, metabolism and nephrology reached the 2002 patient number in 2003. The ARIMA (2,1,0) model was the most suitable for outpatient volume in pre-SARS year. The MAPE of the ARIMA (2,1,0) model for the pre-SARS year was 6.9%, and 43.2%, 10.6%, 6.2% for following 3 years. CONCLUSION: This study demonstrates that if a hospital is completely shut down due to SARS or a similar disease, the impact is longer than previous reported and different departments may experience different recover periods. The findings of this study identify subspecialties that are particularly vulnerable in an infectious disease designated hospital and such hospitals need to consider which subspecialties should be included in their medical structure.",2008 Nov 6,"['Chu, Dachen', 'Chen, Ran-Chou', 'Ku, Chia-Yu', 'Chou, Pesus']",BMC Health Serv Res,,,True
323c52cddef7a35732afdc41dac2a1aa6cb60f16,PMC,"Bayesian, Maximum Parsimony and UPGMA Models for Inferring the Phylogenies of Antelopes Using Mitochondrial Markers",,PMC2614192,19204824,CC BY,"This investigation was aimed to compare the inference of antelope phylogenies resulting from the 16S rRNA, cytochrome-b (cyt-b) and d-loop segments of mitochondrial DNA using three different computational models including Bayesian (BA), maximum parsimony (MP) and unweighted pair group method with arithmetic mean (UPGMA). The respective nucleotide sequences of three Oryx species (Oryx leucoryx, Oryx dammah and Oryx gazella) and an out-group (Addax nasomaculatus) were aligned and subjected to BA, MP and UPGMA models for comparing the topologies of respective phylogenetic trees. The 16S rRNA region possessed the highest frequency of conserved sequences (97.65%) followed by cyt-b (94.22%) and d-loop (87.29%). There were few transitions (2.35%) and none transversions in 16S rRNA as compared to cyt-b (5.61% transitions and 0.17% transversions) and d-loop (11.57% transitions and 1.14% transversions) while comparing the four taxa. All the three mitochondrial segments clearly differentiated the genus Addax from Oryx using the BA or UPGMA models. The topologies of all the gamma-corrected Bayesian trees were identical irrespective of the marker type. The UPGMA trees resulting from 16S rRNA and d-loop sequences were also identical (Oryx dammah grouped with Oryx leucoryx) to Bayesian trees except that the UPGMA tree based on cyt-b showed a slightly different phylogeny (Oryx dammah grouped with Oryx gazella) with a low bootstrap support. However, the MP model failed to differentiate the genus Addax from Oryx. These findings demonstrate the efficiency and robustness of BA and UPGMA methods for phylogenetic analysis of antelopes using mitochondrial markers.",2008 Oct 6,"['Khan, Haseeb A.', 'Arif, Ibrahim A.', 'Bahkali, Ali H.', 'Al Farhan, Ahmad H.', 'Al Homaidan, Ali A.']",Evol Bioinform Online,,,True
18e4bf7e0c2d81caa5795174a4f25d5a035e09b1,PMC,A Novel Peptide Enhances Therapeutic Efficacy of Liposomal Anti-Cancer Drugs in Mice Models of Human Lung Cancer,http://dx.doi.org/10.1371/journal.pone.0004171,PMC2614347,19137069,CC BY,"Lung cancer is the leading cause of cancer-related mortality worldwide. The lack of tumor specificity remains a major drawback for effective chemotherapies and results in dose-limiting toxicities. However, a ligand-mediated drug delivery system should be able to render chemotherapy more specific to tumor cells and less toxic to normal tissues. In this study, we isolated a novel peptide ligand from a phage-displayed peptide library that bound to non-small cell lung cancer (NSCLC) cell lines. The targeting phage bound to several NSCLC cell lines but not to normal cells. Both the targeting phage and the synthetic peptide recognized the surgical specimens of NSCLC with a positive rate of 75% (27 of 36 specimens). In severe combined immunodeficiency (SCID) mice bearing NSCLC xenografts, the targeting phage specifically bound to tumor masses. The tumor homing ability of the targeting phage was inhibited by the cognate synthetic peptide, but not by a control or a WTY-mutated peptide. When the targeting peptide was coupled to liposomes carrying doxorubicin or vinorelbine, the therapeutic index of the chemotherapeutic agents and the survival rates of mice with human lung cancer xenografts markedly increased. Furthermore, the targeting liposomes increased drug accumulation in tumor tissues by 5.7-fold compared with free drugs and enhanced cancer cell apoptosis resulting from a higher concentration of bioavailable doxorubicin. The current study suggests that this tumor-specific peptide may be used to create chemotherapies specifically targeting tumor cells in the treatment of NSCLC and to design targeted gene transfer vectors or it may be used one in the diagnosis of this malignancy.",2009 Jan 12,"['Chang, De-Kuan', 'Lin, Chin-Tarng', 'Wu, Chien-Hsun', 'Wu, Han-Chung']",PLoS One,,,True
c63c4d58d170136b8d3b5a66424b5ac3f73a92d9,PMC,Viral Discovery and Sequence Recovery Using DNA Microarrays,http://dx.doi.org/10.1371/journal.pbio.0000002,PMC261870,14624234,CC BY,"Because of the constant threat posed by emerging infectious diseases and the limitations of existing approaches used to identify new pathogens, there is a great demand for new technological methods for viral discovery. We describe herein a DNA microarray-based platform for novel virus identification and characterization. Central to this approach was a DNA microarray designed to detect a wide range of known viruses as well as novel members of existing viral families; this microarray contained the most highly conserved 70mer sequences from every fully sequenced reference viral genome in GenBank. During an outbreak of severe acute respiratory syndrome (SARS) in March 2003, hybridization to this microarray revealed the presence of a previously uncharacterized coronavirus in a viral isolate cultivated from a SARS patient. To further characterize this new virus, approximately 1 kb of the unknown virus genome was cloned by physically recovering viral sequences hybridized to individual array elements. Sequencing of these fragments confirmed that the virus was indeed a new member of the coronavirus family. This combination of array hybridization followed by direct viral sequence recovery should prove to be a general strategy for the rapid identification and characterization of novel viruses and emerging infectious disease.",2003 Nov 17,"['Wang, David', 'Urisman, Anatoly', 'Liu, Yu-Tsueng', 'Springer, Michael', 'Ksiazek, Thomas G', 'Erdman, Dean D', 'Mardis, Elaine R', 'Hickenbotham, Matthew', 'Magrini, Vincent', 'Eldred, James', 'Latreille, J. Phillipe', 'Wilson, Richard K', 'Ganem, Don', 'DeRisi, Joseph L']",PLoS Biol,,,True
23b1f3033a86c0f53ee90b9ba14634e956f8610b,PMC,"IL-1β, IL-6, and RANTES as Biomarkers of Chikungunya Severity",http://dx.doi.org/10.1371/journal.pone.0004261,PMC2625438,19156204,CC BY,"BACKGROUND: Little is known about the immunopathogenesis of Chikungunya virus. Circulating levels of immune mediators and growth factors were analyzed from patients infected during the first Singaporean Chikungunya fever outbreak in early 2008 to establish biomarkers associated with infection and/or disease severity. METHODS AND FINDINGS: Adult patients with laboratory-confirmed Chikungunya fever infection, who were referred to the Communicable Disease Centre/Tan Tock Seng Hospital during the period from January to February 2008, were included in this retrospective study. Plasma fractions were analyzed using a multiplex-microbead immunoassay. Among the patients, the most common clinical features were fever (100%), arthralgia (90%), rash (50%) and conjunctivitis (40%). Profiles of 30 cytokines, chemokines, and growth factors were able to discriminate the clinical forms of Chikungunya from healthy controls, with patients classified as non-severe and severe disease. Levels of 8 plasma cytokines and 4 growth factors were significantly elevated. Statistical analysis showed that an increase in IL-1β, IL-6 and a decrease in RANTES were associated with disease severity. CONCLUSIONS: This is the first comprehensive report on the production of cytokines, chemokines, and growth factors during acute Chikungunya virus infection. Using these biomarkers, we were able to distinguish between mild disease and more severe forms of Chikungunya fever, thus enabling the identification of patients with poor prognosis and monitoring of the disease.",2009 Jan 21,"['Ng, Lisa F. P.', 'Chow, Angela', 'Sun, Yong-Jiang', 'Kwek, Dyan J. C.', 'Lim, Poh-Lian', 'Dimatatac, Frederico', 'Ng, Lee-Ching', 'Ooi, Eng-Eong', 'Choo, Khar-Heng', 'Her, Zhisheng', 'Kourilsky, Philippe', 'Leo, Yee-Sin']",PLoS One,,,True
672ae4f77f6a2cc3358bfe1e492c268e2dbe3d7a,PMC,Direct Metagenomic Detection of Viral Pathogens in Nasal and Fecal Specimens Using an Unbiased High-Throughput Sequencing Approach,http://dx.doi.org/10.1371/journal.pone.0004219,PMC2625441,19156205,CC BY,"With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a “next-generation” parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu) infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.1–0.25 ml of nasopharyngeal aspirates (N = 3) and fecal specimens (N = 5), and more than 10 µg of cDNA was synthesized. Unbiased high-throughput sequencing of these 8 samples yielded 15,298–32,335 (average 24,738) reads in a single 7.5 h run. In nasopharyngeal samples, although whole genome analysis was not available because the majority (>90%) of reads were host genome–derived, 20–460 Flu-reads were detected, which was sufficient for subtype identification. In fecal samples, bacteria and host cells were removed by centrifugation, resulting in gain of 484–15,260 reads of norovirus sequence (78–98% of the whole genome was covered), except for one specimen that was under-detectable by RT-PCR. These results suggest that our unbiased high-throughput sequencing approach is useful for directly detecting pathogenic viruses without advance genetic information. Although its cost and technological availability make it unlikely that this system will very soon be the diagnostic standard worldwide, this system could be useful for the earlier discovery of novel emerging viruses and bioterrorism, which are difficult to detect with conventional procedures.",2009 Jan 19,"['Nakamura, Shota', 'Yang, Cheng-Song', 'Sakon, Naomi', 'Ueda, Mayo', 'Tougan, Takahiro', 'Yamashita, Akifumi', 'Goto, Naohisa', 'Takahashi, Kazuo', 'Yasunaga, Teruo', 'Ikuta, Kazuyoshi', 'Mizutani, Tetsuya', 'Okamoto, Yoshiko', 'Tagami, Michihira', 'Morita, Ryoji', 'Maeda, Norihiro', 'Kawai, Jun', 'Hayashizaki, Yoshihide', 'Nagai, Yoshiyuki', 'Horii, Toshihiro', 'Iida, Tetsuya', 'Nakaya, Takaaki']",PLoS One,,,True
702a827446e87746c8cd4a843ec2fcf0d306d102,PMC,Direct Metagenomic Detection of Viral Pathogens in Nasal and Fecal Specimens Using an Unbiased High-Throughput Sequencing Approach,http://dx.doi.org/10.1371/journal.pone.0004219,PMC2625441,19156205,CC BY,"With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a “next-generation” parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu) infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.1–0.25 ml of nasopharyngeal aspirates (N = 3) and fecal specimens (N = 5), and more than 10 µg of cDNA was synthesized. Unbiased high-throughput sequencing of these 8 samples yielded 15,298–32,335 (average 24,738) reads in a single 7.5 h run. In nasopharyngeal samples, although whole genome analysis was not available because the majority (>90%) of reads were host genome–derived, 20–460 Flu-reads were detected, which was sufficient for subtype identification. In fecal samples, bacteria and host cells were removed by centrifugation, resulting in gain of 484–15,260 reads of norovirus sequence (78–98% of the whole genome was covered), except for one specimen that was under-detectable by RT-PCR. These results suggest that our unbiased high-throughput sequencing approach is useful for directly detecting pathogenic viruses without advance genetic information. Although its cost and technological availability make it unlikely that this system will very soon be the diagnostic standard worldwide, this system could be useful for the earlier discovery of novel emerging viruses and bioterrorism, which are difficult to detect with conventional procedures.",2009 Jan 19,"['Nakamura, Shota', 'Yang, Cheng-Song', 'Sakon, Naomi', 'Ueda, Mayo', 'Tougan, Takahiro', 'Yamashita, Akifumi', 'Goto, Naohisa', 'Takahashi, Kazuo', 'Yasunaga, Teruo', 'Ikuta, Kazuyoshi', 'Mizutani, Tetsuya', 'Okamoto, Yoshiko', 'Tagami, Michihira', 'Morita, Ryoji', 'Maeda, Norihiro', 'Kawai, Jun', 'Hayashizaki, Yoshihide', 'Nagai, Yoshiyuki', 'Horii, Toshihiro', 'Iida, Tetsuya', 'Nakaya, Takaaki']",PLoS One,,,False
957f2e312b2e2b190e6a2a2b623ecd4b9d4d85ed,PMC,Direct Metagenomic Detection of Viral Pathogens in Nasal and Fecal Specimens Using an Unbiased High-Throughput Sequencing Approach,http://dx.doi.org/10.1371/journal.pone.0004219,PMC2625441,19156205,CC BY,"With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a “next-generation” parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu) infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.1–0.25 ml of nasopharyngeal aspirates (N = 3) and fecal specimens (N = 5), and more than 10 µg of cDNA was synthesized. Unbiased high-throughput sequencing of these 8 samples yielded 15,298–32,335 (average 24,738) reads in a single 7.5 h run. In nasopharyngeal samples, although whole genome analysis was not available because the majority (>90%) of reads were host genome–derived, 20–460 Flu-reads were detected, which was sufficient for subtype identification. In fecal samples, bacteria and host cells were removed by centrifugation, resulting in gain of 484–15,260 reads of norovirus sequence (78–98% of the whole genome was covered), except for one specimen that was under-detectable by RT-PCR. These results suggest that our unbiased high-throughput sequencing approach is useful for directly detecting pathogenic viruses without advance genetic information. Although its cost and technological availability make it unlikely that this system will very soon be the diagnostic standard worldwide, this system could be useful for the earlier discovery of novel emerging viruses and bioterrorism, which are difficult to detect with conventional procedures.",2009 Jan 19,"['Nakamura, Shota', 'Yang, Cheng-Song', 'Sakon, Naomi', 'Ueda, Mayo', 'Tougan, Takahiro', 'Yamashita, Akifumi', 'Goto, Naohisa', 'Takahashi, Kazuo', 'Yasunaga, Teruo', 'Ikuta, Kazuyoshi', 'Mizutani, Tetsuya', 'Okamoto, Yoshiko', 'Tagami, Michihira', 'Morita, Ryoji', 'Maeda, Norihiro', 'Kawai, Jun', 'Hayashizaki, Yoshihide', 'Nagai, Yoshiyuki', 'Horii, Toshihiro', 'Iida, Tetsuya', 'Nakaya, Takaaki']",PLoS One,,,False
df813efa8268b627ab35cc9920d201fe70f45a03,PMC,Direct Metagenomic Detection of Viral Pathogens in Nasal and Fecal Specimens Using an Unbiased High-Throughput Sequencing Approach,http://dx.doi.org/10.1371/journal.pone.0004219,PMC2625441,19156205,CC BY,"With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a “next-generation” parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu) infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.1–0.25 ml of nasopharyngeal aspirates (N = 3) and fecal specimens (N = 5), and more than 10 µg of cDNA was synthesized. Unbiased high-throughput sequencing of these 8 samples yielded 15,298–32,335 (average 24,738) reads in a single 7.5 h run. In nasopharyngeal samples, although whole genome analysis was not available because the majority (>90%) of reads were host genome–derived, 20–460 Flu-reads were detected, which was sufficient for subtype identification. In fecal samples, bacteria and host cells were removed by centrifugation, resulting in gain of 484–15,260 reads of norovirus sequence (78–98% of the whole genome was covered), except for one specimen that was under-detectable by RT-PCR. These results suggest that our unbiased high-throughput sequencing approach is useful for directly detecting pathogenic viruses without advance genetic information. Although its cost and technological availability make it unlikely that this system will very soon be the diagnostic standard worldwide, this system could be useful for the earlier discovery of novel emerging viruses and bioterrorism, which are difficult to detect with conventional procedures.",2009 Jan 19,"['Nakamura, Shota', 'Yang, Cheng-Song', 'Sakon, Naomi', 'Ueda, Mayo', 'Tougan, Takahiro', 'Yamashita, Akifumi', 'Goto, Naohisa', 'Takahashi, Kazuo', 'Yasunaga, Teruo', 'Ikuta, Kazuyoshi', 'Mizutani, Tetsuya', 'Okamoto, Yoshiko', 'Tagami, Michihira', 'Morita, Ryoji', 'Maeda, Norihiro', 'Kawai, Jun', 'Hayashizaki, Yoshihide', 'Nagai, Yoshiyuki', 'Horii, Toshihiro', 'Iida, Tetsuya', 'Nakaya, Takaaki']",PLoS One,,,False
418d9b50173b09a1dc9f31d77b539213b63cb9ea,PMC,Direct Metagenomic Detection of Viral Pathogens in Nasal and Fecal Specimens Using an Unbiased High-Throughput Sequencing Approach,http://dx.doi.org/10.1371/journal.pone.0004219,PMC2625441,19156205,CC BY,"With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a “next-generation” parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu) infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.1–0.25 ml of nasopharyngeal aspirates (N = 3) and fecal specimens (N = 5), and more than 10 µg of cDNA was synthesized. Unbiased high-throughput sequencing of these 8 samples yielded 15,298–32,335 (average 24,738) reads in a single 7.5 h run. In nasopharyngeal samples, although whole genome analysis was not available because the majority (>90%) of reads were host genome–derived, 20–460 Flu-reads were detected, which was sufficient for subtype identification. In fecal samples, bacteria and host cells were removed by centrifugation, resulting in gain of 484–15,260 reads of norovirus sequence (78–98% of the whole genome was covered), except for one specimen that was under-detectable by RT-PCR. These results suggest that our unbiased high-throughput sequencing approach is useful for directly detecting pathogenic viruses without advance genetic information. Although its cost and technological availability make it unlikely that this system will very soon be the diagnostic standard worldwide, this system could be useful for the earlier discovery of novel emerging viruses and bioterrorism, which are difficult to detect with conventional procedures.",2009 Jan 19,"['Nakamura, Shota', 'Yang, Cheng-Song', 'Sakon, Naomi', 'Ueda, Mayo', 'Tougan, Takahiro', 'Yamashita, Akifumi', 'Goto, Naohisa', 'Takahashi, Kazuo', 'Yasunaga, Teruo', 'Ikuta, Kazuyoshi', 'Mizutani, Tetsuya', 'Okamoto, Yoshiko', 'Tagami, Michihira', 'Morita, Ryoji', 'Maeda, Norihiro', 'Kawai, Jun', 'Hayashizaki, Yoshihide', 'Nagai, Yoshiyuki', 'Horii, Toshihiro', 'Iida, Tetsuya', 'Nakaya, Takaaki']",PLoS One,,,False
e4d4fde9df50047757fa69030407e861748c0eb3,PMC,Complete genomic sequence analysis of infectious bronchitis virus Ark DPI strain and its evolution by recombination,http://dx.doi.org/10.1186/1743-422X-5-157,PMC2628353,19102764,CC BY,"An infectious bronchitis virus Arkansas DPI (Ark DPI) virulent strain was sequenced, analyzed and compared with many different IBV strains and coronaviruses. The genome of Ark DPI consists of 27,620 nucleotides, excluding poly (A) tail, and comprises ten open reading frames. Comparative sequence analysis of Ark DPI with other IBV strains shows striking similarity to the Conn, Gray, JMK, and Ark 99, which were circulating during that time period. Furthermore, comparison of the Ark genome with other coronaviruses demonstrates a close relationship to turkey coronavirus. Among non-structural genes, the 5'untranslated region (UTR), 3C-like proteinase (3CL(pro)) and the polymerase (RdRp) sequences are 100% identical to the Gray strain. Among structural genes, S1 has 97% identity with Ark 99; S2 has 100% identity with JMK and 96% to Conn; 3b 99%, and 3C to N is 100% identical to Conn strain. Possible recombination sites were found at the intergenic region of spike gene, 3'end of S1 and 3a gene. Independent recombination events may have occurred in the entire genome of Ark DPI, involving four different IBV strains, suggesting that genomic RNA recombination may occur in any part of the genome at number of sites. Hence, we speculate that the Ark DPI strain originated from the Conn strain, but diverged and evolved independently by point mutations and recombination between field strains.",2008 Dec 22,"['Ammayappan, Arun', 'Upadhyay, Chitra', 'Gelb, Jack', 'Vakharia, Vikram N']",Virol J,,,True
859085c2184a2ca5829809632648e1c80c725d2b,PMC,"Sequence space coverage, entropy of genomes and the potential to detect non-human DNA in human samples",http://dx.doi.org/10.1186/1471-2164-9-509,PMC2628393,18973670,CC BY,"BACKGROUND: Genomes store information for building and maintaining organisms. Complete sequencing of many genomes provides the opportunity to study and compare global information properties of those genomes. RESULTS: We have analyzed aspects of the information content of Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Saccharomyces cerevisiae, and Escherichia coli (K-12) genomes. Virtually all possible (> 98%) 12 bp oligomers appear in vertebrate genomes while < 2% of 19 bp oligomers are present. Other species showed different ranges of > 98% to < 2% of possible oligomers in D. melanogaster (12–17 bp), C. elegans (11–17 bp), A. thaliana (11–17 bp), S. cerevisiae (10–16 bp) and E. coli (9–15 bp). Frequencies of unique oligomers in the genomes follow similar patterns. We identified a set of 2.6 M 15-mers that are more than 1 nucleotide different from all 15-mers in the human genome and so could be used as probes to detect microbes in human samples. In a human sample, these probes would detect 100% of the 433 currently fully sequenced prokaryotes and 75% of the 3065 fully sequenced viruses. The human genome is significantly more compact in sequence space than a random genome. We identified the most frequent 5- to 20-mers in the human genome, which may prove useful as PCR primers. We also identified a bacterium, Anaeromyxobacter dehalogenans, which has an exceptionally low diversity of oligomers given the size of its genome and its GC content. The entropy of coding regions in the human genome is significantly higher than non-coding regions and chromosomes. However chromosomes 1, 2, 9, 12 and 14 have a relatively high proportion of coding DNA without high entropy, and chromosome 20 is the opposite with a low frequency of coding regions but relatively high entropy. CONCLUSION: Measures of the frequency of oligomers are useful for designing PCR assays and for identifying chromosomes and organisms with hidden structure that had not been previously recognized. This information may be used to detect novel microbes in human tissues.",2008 Oct 30,"['Liu, Zhandong', 'Venkatesh, Santosh S', 'Maley, Carlo C']",BMC Genomics,,,True
aba67455b71206b20d9b978e994cb571392dd404,PMC,"Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells",http://dx.doi.org/10.1186/1479-5876-6-78,PMC2628881,19077207,CC BY,"Members of the carcinoembryonic antigen family (CEACAMs) are widely expressed, and, depending on the tissue, capable of regulating diverse functions including tumor promotion, tumor suppression, angiogenesis, and neutrophil activation. Four members of this family, CEACAM1, CEACAM8, CEACAM6, and CEACAM3 (recognized by CD66a, CD66b, CD66c, and CD66d mAbs, respectively), are expressed on human neutrophils. CD66a, CD66b, CD66c, and CD66d antibodies each increase neutrophil adhesion to human umbilical vein endothelial cell monolayers. This increase in neutrophil adhesion caused by CD66 antibodies is blocked by CD18 mAbs and is associated with upregulation of CD11/CD18 on the neutrophil surface. To examine potential interactions of CEACAMs in neutrophil signaling, the effects on neutrophil adhesion to human umbilical vein endothelial cells of a set of CD66 mAbs was tested following desensitization to stimulation by various combinations of these mAbs. Addition of a CD66 mAb in the absence of calcium results in desensitization of neutrophils to stimulation by that CD66 mAb. The current data show that desensitization of neutrophils to any two CEACAMs results in selective desensitization to those two CEACAMs, while the cells remain responsive to the other two neutrophil CEACAMs. In addition, cells desensitized to CEACAM-3, -6, and -8 were still responsive to stimulation of CEACAM1 by CD66a mAbs. In contrast, desensitization of cells to CEACAM1 and any two of the other CEACAMs left the cells unresponsive to all CD66 mAbs. Cells desensitized to any combination of CEACAMs remained responsive to the unrelated control protein CD63. Thus, while there is significant independence of the four neutrophil CEACAMs in signaling, CEACAM1 appears to play a unique role among the neutrophil CEACAMs. A model in which CEACAMs dimerize to form signaling complexes could accommodate the observations. Similar interactions may occur in other cells expressing CEACAMs.",2008 Dec 10,"['Skubitz, Keith M', 'Skubitz, Amy PN']",J Transl Med,,,True
7234aab6f4e46d4349fee1e8b38412a5eaebbe3f,PMC,Rift Valley Fever Virus NSs Protein Promotes Post-Transcriptional Downregulation of Protein Kinase PKR and Inhibits eIF2α Phosphorylation,http://dx.doi.org/10.1371/journal.ppat.1000287,PMC2629125,19197350,CC BY,"Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is a negative-stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, and fever and high rates of abortions in livestock. A nonstructural RVFV NSs protein inhibits the transcription of host mRNAs, including interferon-β mRNA, and is a major virulence factor. The present study explored a novel function of the RVFV NSs protein by testing the replication of RVFV lacking the NSs gene in the presence of actinomycin D (ActD) or α-amanitin, both of which served as a surrogate of the host mRNA synthesis suppression function of the NSs. In the presence of the host-transcriptional inhibitors, the replication of RVFV lacking the NSs protein, but not that carrying NSs, induced double-stranded RNA-dependent protein kinase (PKR)–mediated eukaryotic initiation factor (eIF)2α phosphorylation, leading to the suppression of host and viral protein translation. RVFV NSs promoted post-transcriptional downregulation of PKR early in the course of the infection and suppressed the phosphorylated eIF2α accumulation. These data suggested that a combination of RVFV replication and NSs-induced host transcriptional suppression induces PKR-mediated eIF2α phosphorylation, while the NSs facilitates efficient viral translation by downregulating PKR and inhibiting PKR-mediated eIF2α phosphorylation. Thus, the two distinct functions of the NSs, i.e., the suppression of host transcription, including that of type I interferon mRNAs, and the downregulation of PKR, work together to prevent host innate antiviral functions, allowing efficient replication and survival of RVFV in infected mammalian hosts.",2009 Feb 6,"['Ikegami, Tetsuro', 'Narayanan, Krishna', 'Won, Sungyong', 'Kamitani, Wataru', 'Peters, C. J.', 'Makino, Shinji']",PLoS Pathog,,,True
f997749a5fc2672a931ecc329c5f3e1c4c6cae9b,PMC,Bear bile: dilemma of traditional medicinal use and animal protection,http://dx.doi.org/10.1186/1746-4269-5-2,PMC2630947,19138420,CC BY,"Bear bile has been used in Traditional Chinese Medicine (TCM) for thousands of years. Modern investigations showed that it has a wide range of pharmacological actions with little toxicological side effect and the pure compounds have been used for curing hepatic and biliary disorders for decades. However, extensive consumption of bear bile made bears endangered species. In the 1980's, bear farming was established in China to extract bear bile from living bears with ""Free-dripping Fistula Technique"". Bear farming is extremely inhumane and many bears died of illness such as chronic infections and liver cancer. Efforts are now given by non-governmental organizations, mass media and Chinese government to end bear farming ultimately. At the same time, systematic research has to be done to find an alternative for bear bile. In this review, we focused on the literature, laboratory and clinical results related to bear bile and its substitutes or alternative in English and Chinese databases. We examined the substitutes or alternative of bear bile from three aspects: pure compounds derived from bear bile, biles from other animals and herbs from TCM. We then discussed the strategy for stopping the trading of bear bile and issues of bear bile related to potential alternative candidates, existing problems in alternative research and work to be done in the future.",2009 Jan 12,"['Feng, Yibin', 'Siu, Kayu', 'Wang, Ning', 'Ng, Kwan-Ming', 'Tsao, Sai-Wah', 'Nagamatsu, Tadashi', 'Tong, Yao']",J Ethnobiol Ethnomed,,,True
90662d7dc7b09e018829ae2bc13e167b218931d8,PMC,Generation of potent neutralizing human monoclonal antibodies against cytomegalovirus infection from immune B cells,http://dx.doi.org/10.1186/1472-6750-8-85,PMC2631500,19014469,CC BY,"BACKGROUND: Human monoclonal antibodies (mAbs) generated as a result of the immune response are likely to be the most effective therapeutic antibodies, particularly in the case of infectious diseases against which the immune response is protective. Human cytomegalovirus (HCMV) is an ubiquitous opportunistic virus that is the most serious pathogenic agent in transplant patients. The available therapeutic armamentarium (e.g. HCMV hyperimmune globulins or antivirals) is associated with severe side effects and the emergence of drug-resistant strains; therefore, neutralizing human mAb may be a decisive alternative in the prevention of primary and re-activated HCMV infections in these patients. RESULTS: The purpose of this study was to generate neutralizing mAb against HCMV from the immunological repertoire of immune donors. To this aim, we designed an efficient technology relying on two discrete and sequential steps: first, human B-lymphocytes are stimulated with TLR9-agonists and IL-2; second, after both additives are removed, the cells are infected with EBV. Using this strategy we obtained 29 clones secreting IgG neutralizing the HCMV infectivity; four among these were further characterized. All of the mAbs neutralize the infection in different combinations of HCMV strains and target cells, with a potency ~20 fold higher than that of the HCMV hyperimmune globulins, currently used in transplant recipients. Recombinant human monoclonal IgG1 suitable as a prophylactic or therapeutic tool in clinical applications has been generated. CONCLUSION: The technology described has proven to be more reproducible, efficient and rapid than previously reported techniques, and can be adopted at low overall costs by any cell biology laboratory for the development of fully human mAbs for immunotherapeutic uses.",2008 Nov 12,"['Funaro, Ada', 'Gribaudo, Giorgio', 'Luganini, Anna', 'Ortolan, Erika', 'Lo Buono, Nicola', 'Vicenzi, Elisa', 'Cassetta, Luca', 'Landolfo, Santo', 'Buick, Richard', 'Falciola, Luca', 'Murphy, Marianne', 'Garotta, Gianni', 'Malavasi, Fabio']",BMC Biotechnol,,,True
eb824213356f63dbaabe4c3f454914e24d6e6a71,PMC,DDESC: Dragon database for exploration of sodium channels in human,http://dx.doi.org/10.1186/1471-2164-9-622,PMC2631582,19099596,CC BY,"BACKGROUND: Sodium channels are heteromultimeric, integral membrane proteins that belong to a superfamily of ion channels. The mutations in genes encoding for sodium channel proteins have been linked with several inherited genetic disorders such as febrile epilepsy, Brugada syndrome, ventricular fibrillation, long QT syndrome, or channelopathy associated insensitivity to pain. In spite of these significant effects that sodium channel proteins/genes could have on human health, there is no publicly available resource focused on sodium channels that would support exploration of the sodium channel related information. RESULTS: We report here Dragon Database for Exploration of Sodium Channels in Human (DDESC), which provides comprehensive information related to sodium channels regarding different entities, such as ""genes and proteins"", ""metabolites and enzymes"", ""toxins"", ""chemicals with pharmacological effects"", ""disease concepts"", ""human anatomy"", ""pathways and pathway reactions"" and their potential links. DDESC is compiled based on text- and data-mining. It allows users to explore potential associations between different entities related to sodium channels in human, as well as to automatically generate novel hypotheses. CONCLUSION: DDESC is first publicly available resource where the information related to sodium channels in human can be explored at different levels. This database is freely accessible for academic and non-profit users via the worldwide web .",2008 Dec 20,"['Sagar, Sunil', 'Kaur, Mandeep', 'Dawe, Adam', 'Seshadri, Sundararajan Vijayaraghava', 'Christoffels, Alan', 'Schaefer, Ulf', 'Radovanovic, Aleksandar', 'Bajic, Vladimir B']",BMC Genomics,,,True
ad7c54f9cbd1779ce878360e15699bebcbd80cd6,PMC,Molecular characterisation of a bovine-like rotavirus detected from a giraffe,http://dx.doi.org/10.1186/1746-6148-4-46,PMC2632637,19014526,CC BY,"BACKGROUND: Rotavirus (RV), is a member of the Reoviridae family and an important etiological agent of acute viral gastroenteritis in the young. Rotaviruses have a wide host range infecting a broad range of animal species, however little is known about rotavirus infection in exotic animals. In this paper we report the first characterisation of a RV strain from a giraffe calf. RESULTS: This report describes the identification and detailed molecular characterisation of a rotavirus strain detected from a 14-day-old Giraffe (Giraffa camelopardalis), presenting with acute diarrhea. The RV strain detected from the giraffe was characterized molecularly as G10P[11]. Detailed sequence analysis of VP4 and VP7 revealed significant identity at the amino acid sequence level to Bovine RV (BoRV). CONCLUSION: This study demonstrates the need for continuous surveillance of RV strains in various animal populations, which will facilitate the identification of rotavirus hosts not previously reported. Furthermore, extending typical epidemiology studies to a broader host range will contribute to the timely identification of new emerging strain types.",2008 Nov 13,"['Mulherin, Emily', 'Bryan, Jill', 'Beltman, Marijke', ""O'Grady, Luke"", 'Pidgeon, Eugene', 'Garon, Lucie', 'Lloyd, Andrew', 'Bainbridge, John', ""O'Shea, Helen"", 'Whyte, Paul', 'Fanning, Séamus']",BMC Vet Res,,,True
27bafe2069fadba9638ec9eb5ae1afaf3c78cfb8,PMC,Mechanisms of HIV non-progression; robust and sustained CD4+ T-cell proliferative responses to p24 antigen correlate with control of viraemia and lack of disease progression after long-term transfusion-acquired HIV-1 infection,http://dx.doi.org/10.1186/1742-4690-5-112,PMC2633348,19077215,CC BY,"BACKGROUND: Elite non-progressors (plasma viral load <50 copies/ml while antiretroviral naive) constitute a tiny fraction of HIV-infected individuals. After 12 years follow-up of a cohort of 13 long-term non-progressors (LTNP) identified from 135 individuals with transfusion-acquired HIV infection, 5 remained LTNP after 23 to 26 years infection, but only 3 retained elite LTNP status. We examined the mechanisms that differentiated delayed progressors from LTNP in this cohort. RESULTS: A survival advantage was conferred on 12 of 13 subjects, who had at least one host genetic factor (HLA, chemokine receptor or TLR polymorphisms) or viral attenuating factor (defective nef) associated with slow progression. However, antiviral immune responses differentiated the course of disease into and beyond the second decade of infection. A stable p24-specific proliferative response was associated with control of viraemia and retention of non-progressor status, but this p24 response was absent or declined in viraemic subjects. Strong Gag-dominant cytotoxic T lymphocyte (CTL) responses were identified in most LTNP, or Pol dominant-CTL in those with nef-defective HIV infection. CTL were associated with control of viraemia when combined with p24 proliferative responses. However, CTL did not prevent late disease progression. Individuals with sustained viral suppression had CTL recognising numerous Gag epitopes, while strong but restricted responses to one or two immunodominant epitopes was effective for some time, but failed to contain viraemia over the course of this study. Viral escape mutants at a HLA B27-restricted Gag-p24 epitope were detected in only 1 of 3 individuals, whereas declining or negative p24 proliferative responses occurred in all 3 concurrent with an increase in viraemia. CONCLUSION: Detectable viraemia at study entry was predictive of loss of LTNP status and/or disease progression in 6 of 8, and differentiated slow progressors from elite LTNP who retained potent virological control. Sustained immunological suppression of viraemia was independently associated with preserved p24 proliferative responses, regardless of the strength and breadth of the CTL response. A decline in this protective p24 response preceded or correlated with loss of non-progressor status and/or signs of disease progression.",2008 Dec 11,"['Dyer, Wayne B', 'Zaunders, John J', 'Yuan, Fang Fang', 'Wang, Bin', 'Learmont, Jennifer C', 'Geczy, Andrew F', 'Saksena, Nitin K', 'McPhee, Dale A', 'Gorry, Paul R', 'Sullivan, John S']",Retrovirology,,,True
1f3077db9137fe7b7cc858899628f1625cbf0644,PMC,Survey of Slaughtered Pigs for Occurrence of Ochratoxin A and Porcine Nephropathy in Serbia,http://dx.doi.org/10.3390/ijms9112169,PMC2635621,19330066,CC BY,"Samples of blood, kidney and liver were randomly selected from slaughtered pigs (n=90) and analyzed for ochratoxin A by HPLC. In addition, in order to obtain information on the occurrence of nephropathy, histological examinations were carried out. Of the 90 liver samples, 26.6% contained OTA in the range of 0.22–14.5 ng/g. The incidence of OTA in serum and kidney were very similar (31%, 33.3%), with a maximum concentration of 220.8 ng/mL, and 52.5 ng/g, respectively. Histopathological examination of kidneys confirmed tubulopathies with edema and cell vacuolization. In addition, hemorrhages and necrosis of proximal kidney tubules’ cells were found.",2008 Nov 7,"['Milićević, Dragan', 'Jurić, Verica', 'Stefanović, Srđan', 'Jovanović, Milijan', 'Janković, Saša']",Int J Mol Sci,,,True
910a5b6256028ed6f3d360a28f14f49488b56db4,PMC,Recent Developments in Peptide-Based Nucleic Acid Delivery,http://dx.doi.org/10.3390/ijms9071276,PMC2635728,19325804,CC BY,"Despite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among these synthetic vectors are cationic polymers, branched dendrimers, cationic liposomes and cell-penetrating peptides (CPPs). The latter represent an assortment of fairly unrelated sequences essentially characterised by a high content of basic amino acids and a length of 10–30 residues. CPPs are capable of mediating the cellular uptake of hydrophilic macromolecules like peptides and nucleic acids (e.g. siRNAs, aptamers and antisense-oligonucleotides), which are internalised by cells at a very low rate when applied alone. Up to now, numerous sequences have been reported to show cell-penetrating properties and many of them have been used to successfully transport a variety of different cargos into mammalian cells. In recent years, it has become apparent that endocytosis is a major route of internalisation even though the mechanisms underlying the cellular translocation of CPPs are poorly understood and still subject to controversial discussions. In this review, we will summarise the latest developments in peptide-based cellular delivery of nucleic acid cargos. We will discuss different mechanisms of entry, the intracellular fate of the cargo, correlation studies of uptake versus biological activity of the cargo as well as technical problems and pitfalls.",2008 Jul 16,"['Veldhoen, Sandra', 'Laufer, Sandra D.', 'Restle, Tobias']",Int J Mol Sci,,,True
fd955af6faa247ced61613abf842cf3affac6bb2,PMC,Broad-Spectrum Drugs Against Viral Agents,http://dx.doi.org/10.3390/ijms9091561,PMC2635754,19325820,CC BY,"Development of antivirals has focused primarily on vaccines and on treatments for specific viral agents. Although effective, these approaches may be limited in situations where the etiologic agent is unknown or when the target virus has undergone mutation, recombination or reassortment. Augmentation of the innate immune response may be an effective alternative for disease amelioration. Nonspecific, broad-spectrum immune responses can be induced by double-stranded (ds)RNAs such as poly (ICLC), or oligonucleotides (ODNs) containing unmethylated deocycytidyl-deoxyguanosinyl (CpG) motifs. These may offer protection against various bacterial and viral pathogens regardless of their genetic makeup, zoonotic origin or drug resistance.",2008 Sep 1,"['Christopher, Mary E.', 'Wong, Jonathan P.']",Int J Mol Sci,,,True
184c8c4637d343cd81dddd0d3f5e6c922f538afe,PMC,In Very Young Infants Severity of Acute Bronchiolitis Depends On Carried Viruses,http://dx.doi.org/10.1371/journal.pone.0004596,PMC2644758,19240806,CC BY,"BACKGROUND: RT amplification reaction has revealed that various single viruses or viral co-infections caused acute bronchiolitis in infants, and RV appeared to have a growing involvement in early respiratory diseases. Because remaining controversial, the objective was to determine prospectively the respective role of RSV, RV, hMPV and co-infections on the severity of acute bronchiolitis in very young infants. METHODS AND PRINCIPAL FINDINGS: 209 infants (median age: 2.4 months) were enrolled in a prospective study of infants <1 year old, hospitalized for a first episode of bronchiolitis during the winter epidemic season and with no high risk for severe disease. The severity was assessed by recording SaO(2)% at admission, a daily clinical score (scale 0–18), the duration of oxygen supplementation and the length of hospitalization. Viruses were identified in 94.7% by RT amplification reaction: RSV only (45.8%), RV only (7.2%), hMPV only (3.8%), dual RSV/RV (14.3%), and other virus only (2%) or coinfections (9%). RV compared respectively with RSV and dual RSV/RV infection caused a significant less severe disease with a lower clinical score (5[3.2–6] vs. 6[4–8], p = 0.01 and 5.5[5–7], p = 0.04), a shorter time in oxygen supplementation (0[0–1] days vs. 2[0–3] days, p = 0.02 and 2[0–3] days, p = 0.03) and a shorter hospital stay (3[3–4.7] days vs.6 [5–8] days, p = 0.001 and 5[4–6] days, p = 0.04). Conversely, RSV infants had also longer duration of hospitalization in comparison with RSV/RV (p = 0.01) and hMPV (p = 0.04). The multivariate analyses showed that the type of virus carried was independently associated with the duration of hospitalization. CONCLUSION: This study underlined the role of RV in early respiratory diseases, as frequently carried by young infants with a first acute bronchiolitis. RSV caused the more severe disease and conversely RV the lesser severity. No additional effect of dual RSV/RV infection was observed on the severity.",2009 Feb 25,"['Marguet, Christophe', 'Lubrano, Marc', 'Gueudin, Marie', 'Le Roux, Pascal', 'Deschildre, Antoine', 'Forget, Chantal', 'Couderc, Laure', 'Siret, Daniel', 'Donnou, Marie-Dominique', 'Bubenheim, Michael', 'Vabret, Astrid', 'Freymuth, François']",PLoS One,,,True
f3de553d9173bab4ad066e7d00994c165a7d9a41,PMC,The HLA Region and Autoimmune Disease: Associations and Mechanisms of Action,http://dx.doi.org/10.2174/138920207783591690,PMC2647156,19412418,CC BY,"The HLA region encodes several molecules that play key roles in the immune system. Strong association between the HLA region and autoimmune disease (AID) has been established for over fifty years. Association of components of the HLA class II encoded HLA-DRB1-DQA1-DQB1 haplotype has been detected with several AIDs, including rheumatoid arthritis, type 1 diabetes and Graves’ disease. Molecules encoded by this region play a key role in exogenous antigen presentation to CD4+ Th cells, indicating the importance of this pathway in AID initiation and progression. Although other components of the HLA class I and III regions have also been investigated for association with AID, apart from the association of HLA-B*27 with ankylosing spondylitis, it has been difficult to determine additional susceptibility loci independent of the strong linkage disequilibrium (LD) with the HLA class II genes. Recent advances in the statistical analysis of LD and the recruitment of large AID datasets have allowed investigation of the HLA class I and III regions to be re-visited. Association of the HLA class I region, independent of known HLA class II effects, has now been detected for several AIDs, including strong association of HLA-B with type 1 diabetes and HLA-C with multiple sclerosis and Graves’ disease. These results provide further evidence of a possible role for bacterial or viral infection and CD8+ T cells in AID onset. The advances being made in determining the primary associations within the HLA region and AIDs will not only increase our understanding of the mechanisms behind disease pathogenesis but may also aid in the development of novel therapeutic targets in the future.",2007 Nov,"['Gough, S.C.L', 'Simmonds, M.J']",Curr Genomics,,,True
7af827f235679f6d05974e8e5c5ca434642eeda2,PMC,A Discontinuous RNA Platform Mediates RNA Virus Replication: Building an Integrated Model for RNA–based Regulation of Viral Processes,http://dx.doi.org/10.1371/journal.ppat.1000323,PMC2648310,19266082,CC BY,"Plus-strand RNA viruses contain RNA elements within their genomes that mediate a variety of fundamental viral processes. The traditional view of these elements is that of local RNA structures. This perspective, however, is changing due to increasing discoveries of functional viral RNA elements that are formed by long-range RNA–RNA interactions, often spanning thousands of nucleotides. The plus-strand RNA genomes of tombusviruses exemplify this concept by possessing different long-range RNA–RNA interactions that regulate both viral translation and transcription. Here we report that a third fundamental tombusvirus process, viral genome replication, requires a long-range RNA–based interaction spanning ∼3000 nts. In vivo and in vitro analyses suggest that the discontinuous RNA platform formed by the interaction facilitates efficient assembly of the viral RNA replicase. This finding has allowed us to build an integrated model for the role of global RNA structure in regulating the reproduction of a eukaryotic RNA virus, and the insights gained have extended our understanding of the multifunctional nature of viral RNA genomes.",2009 Mar 6,"['Wu, Baodong', 'Pogany, Judit', 'Na, Hong', 'Nicholson, Beth L.', 'Nagy, Peter D.', 'White, K. Andrew']",PLoS Pathog,,,True
e5e8b3747bbc731a8ef8ceab73882ec5cff818ef,PMC,A Discontinuous RNA Platform Mediates RNA Virus Replication: Building an Integrated Model for RNA–based Regulation of Viral Processes,http://dx.doi.org/10.1371/journal.ppat.1000323,PMC2648310,19266082,CC BY,"Plus-strand RNA viruses contain RNA elements within their genomes that mediate a variety of fundamental viral processes. The traditional view of these elements is that of local RNA structures. This perspective, however, is changing due to increasing discoveries of functional viral RNA elements that are formed by long-range RNA–RNA interactions, often spanning thousands of nucleotides. The plus-strand RNA genomes of tombusviruses exemplify this concept by possessing different long-range RNA–RNA interactions that regulate both viral translation and transcription. Here we report that a third fundamental tombusvirus process, viral genome replication, requires a long-range RNA–based interaction spanning ∼3000 nts. In vivo and in vitro analyses suggest that the discontinuous RNA platform formed by the interaction facilitates efficient assembly of the viral RNA replicase. This finding has allowed us to build an integrated model for the role of global RNA structure in regulating the reproduction of a eukaryotic RNA virus, and the insights gained have extended our understanding of the multifunctional nature of viral RNA genomes.",2009 Mar 6,"['Wu, Baodong', 'Pogany, Judit', 'Na, Hong', 'Nicholson, Beth L.', 'Nagy, Peter D.', 'White, K. Andrew']",PLoS Pathog,,,False
ec84301b786a7e9bb2745f5a4141a69e484a92f3,PMC,Smallpox and Season: Reanalysis of Historical Data,http://dx.doi.org/10.1155/2009/591935,PMC2648660,19266090,CC BY,"Seasonal variation in smallpox transmission is one of the most pressing ecological questions and is relevant to bioterrorism preparedness. The present study reanalyzed 7 historical datasets which recorded monthly cases or deaths. In addition to time series analyses of reported data, an estimation and spectral analysis of the effective reproduction number at calendar time t, R(t), were made. Meteorological variables were extracted from a report in India from 1890–1921 and compared with smallpox mortality as well as R(t). Annual cycles of smallpox transmission were clearly shown not only in monthly reports but also in the estimates of R(t). Even short-term epidemic data clearly exhibited an annual peak every January. Both mortality and R(t) revealed significant negative association (P < .01) and correlation (P < .01), respectively, with humidity. These findings suggest that smallpox transmission greatly varies with season and is most likely enhanced by dry weather.",2009 Jan 4,"['Nishiura, Hiroshi', 'Kashiwagi, Tomoko']",Interdiscip Perspect Infect Dis,,,True
741b4227809cd635e7f0f06cf4f70331a9764b5f,PMC,A computational analysis of SARS cysteine proteinase-octapeptide substrate interaction: implication for structure and active site binding mechanism,http://dx.doi.org/10.1186/1471-2105-10-S1-S48,PMC2648740,19208150,CC BY,"BACKGROUND: SARS coronavirus main proteinase (SARS CoVMpro) is an important enzyme for the replication of Severe Acute Respiratory Syndrome virus. The active site region of SARS CoVMpro is divided into 8 subsites. Understanding the binding mode of SARS CoVMpro with a specific substrate is useful and contributes to structural-based drug design. The purpose of this research is to investigate the binding mode between the SARS CoVMpro and two octapeptides, especially in the region of the S3 subsite, through a molecular docking and molecular dynamics (MD) simulation approach. RESULTS: The one turn α-helix chain (residues 47–54) of the SARS CoVMpro was directly involved in the induced-fit model of the enzyme-substrate complex. The S3 subsite of the enzyme had a negatively charged region due to the presence of Glu47. During MD simulations, Glu47 of the enzyme was shown to play a key role in electrostatic bonding with the P3Lys of the octapeptide. CONCLUSION: MD simulations were carried out on the SARS CoVMpro-octapeptide complex. The hypothesis proposed that Glu47 of SARS CoVMpro is an important residue in the S3 subsite and is involved in binding with P3Lys of the octapeptide.",2009 Jan 30,"['Phakthanakanok, Krongsakda', 'Ratanakhanokchai, Khanok', 'Kyu, Khin Lay', 'Sompornpisut, Pornthep', 'Watts, Aaron', 'Pinitglang, Surapong']",BMC Bioinformatics,,,True
084df43c5fc9b52ac507f090c6d892b69e5b0999,PMC,Feline Leukemia Virus and Other Pathogens as Important Threats to the Survival of the Critically Endangered Iberian Lynx (Lynx pardinus),http://dx.doi.org/10.1371/journal.pone.0004744,PMC2649436,19270739,CC BY,"BACKGROUND: The Iberian lynx (Lynx pardinus) is considered the most endangered felid species in the world. In order to save this species, the Spanish authorities implemented a captive breeding program recruiting lynxes from the wild. In this context, a retrospective survey on prevalence of selected feline pathogens in free-ranging lynxes was initiated. METHODOLOGY/ PRINCIPAL FINDINGS: We systematically analyzed the prevalence and importance of seven viral, one protozoan (Cytauxzoon felis), and several bacterial (e.g., hemotropic mycoplasma) infections in 77 of approximately 200 remaining free-ranging Iberian lynxes of the Doñana and Sierra Morena areas, in Southern Spain, between 2003 and 2007. With the exception of feline immunodeficiency virus (FIV), evidence of infection by all tested feline pathogens was found in Iberian lynxes. Fourteen lynxes were feline leukemia virus (FeLV) provirus-positive; eleven of these were antigenemic (FeLV p27 positive). All 14 animals tested negative for other viral infections. During a six-month period in 2007, six of the provirus-positive antigenemic lynxes died. Infection with FeLV but not with other infectious agents was associated with mortality (p<0.001). Sequencing of the FeLV surface glycoprotein gene revealed a common origin for ten of the eleven samples. The ten sequences were closely related to FeLV-A/61E, originally isolated from cats in the USA. Endogenous FeLV sequences were not detected. CONCLUSIONS/SIGNIFICANCE: It was concluded that the FeLV infection most likely originated from domestic cats invading the lynx's habitats. Data available regarding the time frame, co-infections, and outcome of FeLV-infections suggest that, in contrast to the domestic cat, the FeLV strain affecting the lynxes in 2007 is highly virulent to this species. Our data argue strongly for vaccination of lynxes and domestic cats in and around lynx's habitats in order to prevent further spread of the virus as well as reduction the domestic cat population if the lynx population is to be maintained.",2009 Mar 9,"['Meli, Marina L.', 'Cattori, Valentino', 'Martínez, Fernando', 'López, Guillermo', 'Vargas, Astrid', 'Simón, Miguel A.', 'Zorrilla, Irene', 'Muñoz, Alvaro', 'Palomares, Francisco', 'López-Bao, Jose V.', 'Pastor, Josep', 'Tandon, Ravi', 'Willi, Barbara', 'Hofmann-Lehmann, Regina', 'Lutz, Hans']",PLoS One,,,True
c3f83fef0e35a95a6ff12ffacf58969db6172761,PMC,Ciliary Beating Recovery in Deficient Human Airway Epithelial Cells after Lentivirus Ex Vivo Gene Therapy,http://dx.doi.org/10.1371/journal.pgen.1000422,PMC2650261,19300481,CC BY,"Primary Ciliary Dyskinesia is a heterogeneous genetic disease that is characterized by cilia dysfunction of the epithelial cells lining the respiratory tracts, resulting in recurrent respiratory tract infections. Despite lifelong physiological therapy and antibiotics, the lungs of affected patients are progressively destroyed, leading to respiratory insufficiency. Recessive mutations in Dynein Axonemal Intermediate chain type 1 (DNAI1) gene have been described in 10% of cases of Primary Ciliary Dyskinesia. Our goal was to restore normal ciliary beating in DNAI1–deficient human airway epithelial cells. A lentiviral vector based on Simian Immunodeficiency Virus pseudotyped with Vesicular Stomatitis Virus Glycoprotein was used to transduce cultured human airway epithelial cells with a cDNA of DNAI1 driven by the Elongation Factor 1 promoter. Transcription and translation of the transduced gene were tested by RT–PCR and western blot, respectively. Human airway epithelial cells that were DNAI1–deficient due to compound heterozygous mutations, and consequently had immotile cilia and no outer dynein arm, were transduced by the lentivirus. Cilia beating was recorded and electron microscopy of the cilia was performed. Transcription and translation of the transduced DNAI1 gene were detected in human cells treated with the lentivirus. In addition, immotile cilia recovered a normal beat and outer dynein arms reappeared. We demonstrated that it is possible to obtain a normalization of ciliary beat frequency of deficient human airway epithelial cells by using a lentivirus to transduce cells with the therapeutic gene. This preliminary step constitutes a conceptual proof that is indispensable in the perspective of Primary Ciliary Dyskinesia's in vivo gene therapy. This is the first time that recovery of cilia beating is demonstrated in this disease.",2009 Mar 20,"['Chhin, Brigitte', 'Negre, Didier', 'Merrot, Olivier', 'Pham, Jacqueline', 'Tourneur, Yves', 'Ressnikoff, Denis', 'Jaspers, Martine', 'Jorissen, Mark', 'Cosset, François-Loïc', 'Bouvagnet, Patrice']",PLoS Genet,,,True
ce4252922cce80f4284eae7607b1967b35596ef5,PMC,Ciliary Beating Recovery in Deficient Human Airway Epithelial Cells after Lentivirus Ex Vivo Gene Therapy,http://dx.doi.org/10.1371/journal.pgen.1000422,PMC2650261,19300481,CC BY,"Primary Ciliary Dyskinesia is a heterogeneous genetic disease that is characterized by cilia dysfunction of the epithelial cells lining the respiratory tracts, resulting in recurrent respiratory tract infections. Despite lifelong physiological therapy and antibiotics, the lungs of affected patients are progressively destroyed, leading to respiratory insufficiency. Recessive mutations in Dynein Axonemal Intermediate chain type 1 (DNAI1) gene have been described in 10% of cases of Primary Ciliary Dyskinesia. Our goal was to restore normal ciliary beating in DNAI1–deficient human airway epithelial cells. A lentiviral vector based on Simian Immunodeficiency Virus pseudotyped with Vesicular Stomatitis Virus Glycoprotein was used to transduce cultured human airway epithelial cells with a cDNA of DNAI1 driven by the Elongation Factor 1 promoter. Transcription and translation of the transduced gene were tested by RT–PCR and western blot, respectively. Human airway epithelial cells that were DNAI1–deficient due to compound heterozygous mutations, and consequently had immotile cilia and no outer dynein arm, were transduced by the lentivirus. Cilia beating was recorded and electron microscopy of the cilia was performed. Transcription and translation of the transduced DNAI1 gene were detected in human cells treated with the lentivirus. In addition, immotile cilia recovered a normal beat and outer dynein arms reappeared. We demonstrated that it is possible to obtain a normalization of ciliary beat frequency of deficient human airway epithelial cells by using a lentivirus to transduce cells with the therapeutic gene. This preliminary step constitutes a conceptual proof that is indispensable in the perspective of Primary Ciliary Dyskinesia's in vivo gene therapy. This is the first time that recovery of cilia beating is demonstrated in this disease.",2009 Mar 20,"['Chhin, Brigitte', 'Negre, Didier', 'Merrot, Olivier', 'Pham, Jacqueline', 'Tourneur, Yves', 'Ressnikoff, Denis', 'Jaspers, Martine', 'Jorissen, Mark', 'Cosset, François-Loïc', 'Bouvagnet, Patrice']",PLoS Genet,,,True
a5e0a0ed5bd96d5d8bda79b3b77b68ade21eaee0,PMC,Novel concepts in virally induced asthma,http://dx.doi.org/10.1186/1476-7961-7-2,PMC2651109,19154602,CC BY,"Viruses are the predominant infectious cause of asthma exacerbations in the developed world. In addition, recent evidence strongly suggests that viral infections may also have a causal role in the development of childhood asthma. In this article, we will briefly describe the general perception of how the link between infections and asthma has changed over the last century, and then focus on very recent developments that have provided new insights into the contribution of viruses to asthma pathogenesis. Highlighted areas include the contribution of severe early life viral infections to asthma inception, genetic determinants of severe viral infections in infancy, the differences in innate and adaptive immune system cytokine responses to viral infection between asthmatic and nonasthmatic subjects, and a potential vaccine strategy to prevent severe early life virally-induced illness.",2009 Jan 20,"['Huckabee, Matthew M', 'Peebles, R Stokes']",Clin Mol Allergy,,,True
31b039f27dbcd96df12be89f281f576d26fe80e1,PMC,The Complete Genome and Proteome of Laribacter hongkongensis Reveal Potential Mechanisms for Adaptations to Different Temperatures and Habitats,http://dx.doi.org/10.1371/journal.pgen.1000416,PMC2652115,19283063,CC BY,"Laribacter hongkongensis is a newly discovered Gram-negative bacillus of the Neisseriaceae family associated with freshwater fish–borne gastroenteritis and traveler's diarrhea. The complete genome sequence of L. hongkongensis HLHK9, recovered from an immunocompetent patient with severe gastroenteritis, consists of a 3,169-kb chromosome with G+C content of 62.35%. Genome analysis reveals different mechanisms potentially important for its adaptation to diverse habitats of human and freshwater fish intestines and freshwater environments. The gene contents support its phenotypic properties and suggest that amino acids and fatty acids can be used as carbon sources. The extensive variety of transporters, including multidrug efflux and heavy metal transporters as well as genes involved in chemotaxis, may enable L. hongkongensis to survive in different environmental niches. Genes encoding urease, bile salts efflux pump, adhesin, catalase, superoxide dismutase, and other putative virulence factors—such as hemolysins, RTX toxins, patatin-like proteins, phospholipase A1, and collagenases—are present. Proteomes of L. hongkongensis HLHK9 cultured at 37°C (human body temperature) and 20°C (freshwater habitat temperature) showed differential gene expression, including two homologous copies of argB, argB-20, and argB-37, which encode two isoenzymes of N-acetyl-L-glutamate kinase (NAGK)—NAGK-20 and NAGK-37—in the arginine biosynthesis pathway. NAGK-20 showed higher expression at 20°C, whereas NAGK-37 showed higher expression at 37°C. NAGK-20 also had a lower optimal temperature for enzymatic activities and was inhibited by arginine probably as negative-feedback control. Similar duplicated copies of argB are also observed in bacteria from hot springs such as Thermus thermophilus, Deinococcus geothermalis, Deinococcus radiodurans, and Roseiflexus castenholzii, suggesting that similar mechanisms for temperature adaptation may be employed by other bacteria. Genome and proteome analysis of L. hongkongensis revealed novel mechanisms for adaptations to survival at different temperatures and habitats.",2009 Mar 13,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Tse, Herman', 'Teng, Jade L. L.', 'Curreem, Shirly O. T.', 'Tsang, Alan K. L.', 'Fan, Rachel Y. Y.', 'Wong, Gilman K. M.', 'Huang, Yi', 'Loman, Nicholas J.', 'Snyder, Lori A. S.', 'Cai, James J.', 'Huang, Jian-Dong', 'Mak, William', 'Pallen, Mark J.', 'Lok, Si', 'Yuen, Kwok-Yung']",PLoS Genet,,,True
3dd8a16b73bc8a692aa50ed576665adfe598db84,PMC,The Complete Genome and Proteome of Laribacter hongkongensis Reveal Potential Mechanisms for Adaptations to Different Temperatures and Habitats,http://dx.doi.org/10.1371/journal.pgen.1000416,PMC2652115,19283063,CC BY,"Laribacter hongkongensis is a newly discovered Gram-negative bacillus of the Neisseriaceae family associated with freshwater fish–borne gastroenteritis and traveler's diarrhea. The complete genome sequence of L. hongkongensis HLHK9, recovered from an immunocompetent patient with severe gastroenteritis, consists of a 3,169-kb chromosome with G+C content of 62.35%. Genome analysis reveals different mechanisms potentially important for its adaptation to diverse habitats of human and freshwater fish intestines and freshwater environments. The gene contents support its phenotypic properties and suggest that amino acids and fatty acids can be used as carbon sources. The extensive variety of transporters, including multidrug efflux and heavy metal transporters as well as genes involved in chemotaxis, may enable L. hongkongensis to survive in different environmental niches. Genes encoding urease, bile salts efflux pump, adhesin, catalase, superoxide dismutase, and other putative virulence factors—such as hemolysins, RTX toxins, patatin-like proteins, phospholipase A1, and collagenases—are present. Proteomes of L. hongkongensis HLHK9 cultured at 37°C (human body temperature) and 20°C (freshwater habitat temperature) showed differential gene expression, including two homologous copies of argB, argB-20, and argB-37, which encode two isoenzymes of N-acetyl-L-glutamate kinase (NAGK)—NAGK-20 and NAGK-37—in the arginine biosynthesis pathway. NAGK-20 showed higher expression at 20°C, whereas NAGK-37 showed higher expression at 37°C. NAGK-20 also had a lower optimal temperature for enzymatic activities and was inhibited by arginine probably as negative-feedback control. Similar duplicated copies of argB are also observed in bacteria from hot springs such as Thermus thermophilus, Deinococcus geothermalis, Deinococcus radiodurans, and Roseiflexus castenholzii, suggesting that similar mechanisms for temperature adaptation may be employed by other bacteria. Genome and proteome analysis of L. hongkongensis revealed novel mechanisms for adaptations to survival at different temperatures and habitats.",2009 Mar 13,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Tse, Herman', 'Teng, Jade L. L.', 'Curreem, Shirly O. T.', 'Tsang, Alan K. L.', 'Fan, Rachel Y. Y.', 'Wong, Gilman K. M.', 'Huang, Yi', 'Loman, Nicholas J.', 'Snyder, Lori A. S.', 'Cai, James J.', 'Huang, Jian-Dong', 'Mak, William', 'Pallen, Mark J.', 'Lok, Si', 'Yuen, Kwok-Yung']",PLoS Genet,,,False
b710adc78b56eb091aa40bc4cf5bc015e3f567e4,PMC,Genetic Drift of HIV Populations in Culture,http://dx.doi.org/10.1371/journal.pgen.1000431,PMC2652835,19300501,CC BY,"Populations of Human Immunodeficiency Virus type 1 (HIV-1) undergo a surprisingly large amount of genetic drift in infected patients despite very large population sizes, which are predicted to be mostly deterministic. Several models have been proposed to explain this phenomenon, but all of them implicitly assume that the process of virus replication itself does not contribute to genetic drift. We developed an assay to measure the amount of genetic drift for HIV populations replicating in cell culture. The assay relies on creation of HIV populations of known size and measurements of variation in frequency of a neutral allele. Using this assay, we show that HIV undergoes approximately ten times more genetic drift than would be expected from its population size, which we defined as the number of infected cells in the culture. We showed that a large portion of the increase in genetic drift is due to non-synchronous infection of target cells. When infections are synchronized, genetic drift for the virus is only 3-fold higher than expected from its population size. Thus, the stochastic nature of biological processes involved in viral replication contributes to increased genetic drift in HIV populations. We propose that appreciation of these effects will allow better understanding of the evolutionary forces acting on HIV in infected patients.",2009 Mar 20,"['Voronin, Yegor', 'Holte, Sarah', 'Overbaugh, Julie', 'Emerman, Michael']",PLoS Genet,,,True
319da4b3a356bea3794d401087176bcd055ba23d,PMC,Transmission Dynamics and Prospects for the Elimination of Canine Rabies,http://dx.doi.org/10.1371/journal.pbio.1000053,PMC2653555,19278295,CC BY,"Rabies has been eliminated from domestic dog populations in Western Europe and North America, but continues to kill many thousands of people throughout Africa and Asia every year. A quantitative understanding of transmission dynamics in domestic dog populations provides critical information to assess whether global elimination of canine rabies is possible. We report extensive observations of individual rabid animals in Tanzania and generate a uniquely detailed analysis of transmission biology, which explains important epidemiological features, including the level of variation in epidemic trajectories. We found that the basic reproductive number for rabies, R(0), is very low in our study area in rural Africa (∼1.2) and throughout its historic global range (<2). This finding provides strong support for the feasibility of controlling endemic canine rabies by vaccination, even near wildlife areas with large wild carnivore populations. However, we show that rapid turnover of domestic dog populations has been a major obstacle to successful control in developing countries, thus regular pulse vaccinations will be required to maintain population-level immunity between campaigns. Nonetheless our analyses suggest that with sustained, international commitment, global elimination of rabies from domestic dog populations, the most dangerous vector to humans, is a realistic goal.",2009 Mar 10,"['Hampson, Katie', 'Dushoff, Jonathan', 'Cleaveland, Sarah', 'Haydon, Daniel T', 'Kaare, Magai', 'Packer, Craig', 'Dobson, Andy']",PLoS Biol,,,True
7379b8c28321b7f9c78d2b4d35109a87b35cf883,PMC,Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding,http://dx.doi.org/10.1371/journal.pone.0004908,PMC2653722,19287488,CC BY,"Coronavirus M protein is an essential component of virion and plays pivotal roles in virion assembly, budding and maturation. The M protein is integrated into the viral envelope with three transmembrane domains flanked by a short amino-terminal ectodomain and a large carboxy-terminal endodomain. In this study, we showed co-purification of the M protein from coronavirus infectious bronchitis virus (IBV) with actin. To understand the cellular factors that may be involved in virion assembly, budding and maturation processes, IBV M was used as the bait in a yeast two-hybrid screen, resulting in the identification of β-actin as a potentially interacting partner. This interaction was subsequently confirmed by coimmunoprecipitation and immunofluorescence microscopy in mammalian cells, and mutation of amino acids A159 and K160 on the M protein abolished the interaction. Introduction of the A159-K160 mutation into an infectious IBV clone system blocks the infectivity of the clone, although viral RNA replication and subgenomic mRNA transcription were actively detected. Disruption of actin filaments with cell-permeable agent cytochalasin D at early stages of the infection cycle led to the detection of viral protein synthesis in infected cells but not release of virus particles to the cultured media. However, the same treatment at late stages of the infection cycle did not affect the release of virus particles to the media, suggesting that disruption of the actin filaments might block virion assembly and budding, but not release of the virus particles. This study reveals an essential function of actin in the replication cycle of coronavirus.",2009 Mar 16,"['Wang, Jibin', 'Fang, Shouguo', 'Xiao, Han', 'Chen, Bo', 'Tam, James P.', 'Liu, Ding Xiang']",PLoS One,,,True
c337fa83ebb25e4600c0f9333ee0cb0fa938e947,PMC,Healthcare workers' attitudes to working during pandemic influenza: a qualitative study,http://dx.doi.org/10.1186/1471-2458-9-56,PMC2654560,19216738,CC BY,"BACKGROUND: Healthcare workers (HCWs) will play a key role in any response to pandemic influenza, and the UK healthcare system's ability to cope during an influenza pandemic will depend, to a large extent, on the number of HCWs who are able and willing to work through the crisis. UK emergency planning will be improved if planners have a better understanding of the reasons UK HCWs may have for their absenteeism, and what might motivate them to work during an influenza pandemic. This paper reports the results of a qualitative study that explored UK HCWs' views (n = 64) about working during an influenza pandemic, in order to identify factors that might influence their willingness and ability to work and to identify potential sources of any perceived duty on HCWs to work. METHODS: A qualitative study, using focus groups (n = 9) and interviews (n = 5). RESULTS: HCWs across a range of roles and grades tended to feel motivated by a sense of obligation to work through an influenza pandemic. A number of significant barriers that may prevent them from doing so were also identified. Perceived barriers to the ability to work included being ill oneself, transport difficulties, and childcare responsibilities. Perceived barriers to the willingness to work included: prioritising the wellbeing of family members; a lack of trust in, and goodwill towards, the NHS; a lack of information about the risks and what is expected of them during the crisis; fear of litigation; and the feeling that employers do not take the needs of staff seriously. Barriers to ability and barriers to willingness, however, are difficult to separate out. CONCLUSION: Although our participants tended to feel a general obligation to work during an influenza pandemic, there are barriers to working, which, if generalisable, may significantly reduce the NHS workforce during a pandemic. The barriers identified are both barriers to willingness and to ability. This suggests that pandemic planning needs to take into account the possibility that staff may be absent for reasons beyond those currently anticipated in UK planning documents. In particular, staff who are physically able to attend work may nonetheless be unwilling to do so. Although there are some barriers that cannot be mitigated by employers (such as illness, transport infrastructure etc.), there are a number of remedial steps that can be taken to lesson the impact of others (providing accommodation, building reciprocity, provision of information and guidance etc). We suggest that barriers to working lie along an ability/willingness continuum, and that absenteeism may be reduced by taking steps to prevent barriers to willingness becoming perceived barriers to ability.",2009 Feb 12,"['Ives, Jonathan', 'Greenfield, Sheila', 'Parry, Jayne M', 'Draper, Heather', 'Gratus, Christine', 'Petts, Judith I', 'Sorell, Tom', 'Wilson, Sue']",BMC Public Health,,,True
ebc8f68d591a7979fcde0afc4cfcae3a9dac58af,PMC,An Amphipathic α-Helix Controls Multiple Roles of Brome Mosaic Virus Protein 1a in RNA Replication Complex Assembly and Function,http://dx.doi.org/10.1371/journal.ppat.1000351,PMC2654722,19325881,CC BY,"Brome mosaic virus (BMV) protein 1a has multiple key roles in viral RNA replication. 1a localizes to perinuclear endoplasmic reticulum (ER) membranes as a peripheral membrane protein, induces ER membrane invaginations in which RNA replication complexes form, and recruits and stabilizes BMV 2a polymerase (2a(Pol)) and RNA replication templates at these sites to establish active replication complexes. During replication, 1a provides RNA capping, NTPase and possibly RNA helicase functions. Here we identify in BMV 1a an amphipathic α-helix, helix A, and use NMR analysis to define its structure and propensity to insert in hydrophobic membrane-mimicking micelles. We show that helix A is essential for efficient 1a–ER membrane association and normal perinuclear ER localization, and that deletion or mutation of helix A abolishes RNA replication. Strikingly, mutations in helix A give rise to two dramatically opposite 1a function phenotypes, implying that helix A acts as a molecular switch regulating the intricate balance between separable 1a functions. One class of helix A deletions and amino acid substitutions markedly inhibits 1a–membrane association and abolishes ER membrane invagination, viral RNA template recruitment, and replication, but doubles the 1a-mediated increase in 2a(Pol) accumulation. The second class of helix A mutations not only maintains efficient 1a–membrane association but also amplifies the number of 1a-induced membrane invaginations 5- to 8-fold and enhances viral RNA template recruitment, while failing to stimulate 2a(Pol) accumulation. The results provide new insights into the pathways of RNA replication complex assembly and show that helix A is critical for assembly and function of the viral RNA replication complex, including its central role in targeting replication components and controlling modes of 1a action.",2009 Mar 27,"['Liu, Ling', 'Westler, William M.', 'den Boon, Johan A.', 'Wang, Xiaofeng', 'Diaz, Arturo', 'Steinberg, H. Adam', 'Ahlquist, Paul']",PLoS Pathog,,,True
0596a285261bc529af5a4bea0447bc838f45866f,PMC,Viruses and thyroiditis: an update,http://dx.doi.org/10.1186/1743-422X-6-5,PMC2654877,19138419,CC BY,"Viral infections are frequently cited as a major environmental factor involved in subacute thyroiditis and autoimmune thyroid diseases This review examines the data related to the role of viruses in the development of thyroiditis. Our research has been focused on human data. We have reviewed virological data for each type of thyroiditis at different levels of evidence; epidemiological data, serological data or research on circulating viruses, direct evidence of thyroid tissue infection. Interpretation of epidemiological and serological data must be cautious as they don't prove that this pathogen is responsible for the disease. However, direct evidence of the presence of viruses or their components in the organ are available for retroviruses (HFV) and mumps in subacute thyroiditis, for retroviruses (HTLV-1, HFV, HIV and SV40) in Graves's disease and for HTLV-1, enterovirus, rubella, mumps virus, HSV, EBV and parvovirus in Hashimoto's thyroiditis. However, it remains to determine whether they are responsible for thyroid diseases or whether they are just innocent bystanders. Further studies are needed to clarify the relationship between viruses and thyroid diseases, in order to develop new strategies for prevention and/or treatment.",2009 Jan 12,"['Desailloud, Rachel', 'Hober, Didier']",Virol J,,,True
3f842ddde61088937e203ddec6ace954e479499e,PMC,Detection of genetically modified organisms (GMOs) using isothermal amplification of target DNA sequences,http://dx.doi.org/10.1186/1472-6750-9-7,PMC2656497,19187544,CC BY,"BACKGROUND: The most common method of GMO detection is based upon the amplification of GMO-specific DNA amplicons using the polymerase chain reaction (PCR). Here we have applied the loop-mediated isothermal amplification (LAMP) method to amplify GMO-related DNA sequences, 'internal' commonly-used motifs for controlling transgene expression and event-specific (plant-transgene) junctions. RESULTS: We have tested the specificity and sensitivity of the technique for use in GMO studies. Results show that detection of 0.01% GMO in equivalent background DNA was possible and dilutions of template suggest that detection from single copies of the template may be possible using LAMP. CONCLUSION: This work shows that GMO detection can be carried out using LAMP for routine screening as well as for specific events detection. Moreover, the sensitivity and ability to amplify targets, even with a high background of DNA, here demonstrated, highlights the advantages of this isothermal amplification when applied for GMO detection.",2009 Feb 2,"['Lee, David', 'La Mura, Maurizio', 'Allnutt, Theo R', 'Powell, Wayne']",BMC Biotechnol,,,True
ee3d6fcf2ed5408aef9c152f2e7145d916a1baee,PMC,Different inflammatory responses are associated with Ureaplasma parvum-induced UTI and urolith formation,http://dx.doi.org/10.1186/1471-2334-9-9,PMC2656517,19171043,CC BY,"BACKGROUND: Epidemiologic studies show a strong association between Ureaplasmas and urogenital tract disease in humans. Since healthy humans can be colonized with Ureaplasmas, its role as a pathogen remains controversial. In order to begin to define the role of the host in disease, we developed a rodent model of urinary tract infection (UTI) using Fischer 344 (F344) rats. Animals were inoculated with sterile broth, 10(1), 10(3), 10(5), 10(7), or 10(9 )log CFU of a rat-adapted strain of Ureaplasma parvum. RESULTS: Infected animals exhibited two distinct profiles, asymptomatic UTI and UTI complicated with struvite urolithiasis. Inoculum dose of U. parvum affected the incidence of UTI, and 50% to 57% of animals inoculated with ≥ 10(7 )CFU of U. parvum remained infected (p < 0.04). However, inoculum dose did not influence immune response to U. parvum. Asymptomatic UTI was characterized by a minimal immune response that was predominantly monocytic and lymphocytic, with limited lesions, and elevated urinary levels of IFN-γ, IL-18 and MCP-1 (P ≤ 0.02). UTI complicated with struvite formation was characterized by an exaggerated immune response that was mostly neutrophilic (P ≤ 0.0001), with lesions that showed extensive uroepithelial hyperplasia (P ≤ 0.0001), and a predominance of IL-1α, IL-1β, and GRO/KC in the urine (P ≤ 0.02). Animals with asymptomatic UTI also had a significantly high rate of kidney infection (P ≤ 0.0005). CONCLUSION: Complications associated with U. parvum infection are primarily dependent upon host-specific factors rather than Ureaplasma microbial load. The immune response in F344 rats is similar to that which occurs in humans with ureaplasmal associated disease. Therefore, this model of infection is a useful tool for elucidating U. parvum-host interactions that confer UTI and disease.",2009 Jan 26,"['Reyes, Leticia', 'Reinhard, Mary', 'Brown, Mary B']",BMC Infect Dis,,,True
ef872b80cf38917f64c42bfa52a57beb4399897a,PMC,Multivalent HA DNA Vaccination Protects against Highly Pathogenic H5N1 Avian Influenza Infection in Chickens and Mice,http://dx.doi.org/10.1371/journal.pone.0002432,PMC2657001,19293944,CC0,"BACKGROUND: Sustained outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in avian species increase the risk of reassortment and adaptation to humans. The ability to contain its spread in chickens would reduce this threat and help maintain the capacity for egg-based vaccine production. While vaccines offer the potential to control avian disease, a major concern of current vaccines is their potency and inability to protect against evolving avian influenza viruses. METHODOLOGY / PRINCIPAL FINDINGS: The ability of DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. These vaccines elicited antibodies that neutralized multiple strains of HPAI H5N1 when given in combinations containing up to 10 HAs. The response was dose-dependent, and breadth was determined by the choice of the influenza virus HA in the vaccine. Monovalent and trivalent HA vaccines were tested first in mice and conferred protection against lethal H5N1 A/Vietnam/1203/2004 challenge 68 weeks after vaccination. In chickens, protection was observed against heterologous strains of HPAI H5N1 after vaccination with a trivalent H5 serotype DNA vaccine with doses as low as 5 µg DNA given twice either by intramuscular needle injection or with a needle-free device. CONCLUSIONS/SIGNIFICANCE: DNA vaccines offer a generic approach to influenza virus immunization applicable to multiple animal species. In addition, the ability to substitute plasmids encoding different strains enables rapid adaptation of the vaccine to newly evolving field isolates.",2008 Jun 18,"['Rao, Srinivas', 'Kong, Wing-Pui', 'Wei, Chih-Jen', 'Yang, Zhi-Yong', 'Nason, Martha', 'Styles, Darrel', 'DeTolla, Louis J.', 'Sorrell, Erin M.', 'Song, Haichen', 'Wan, Hongquan', 'Ramirez-Nieto, Gloria C.', 'Perez, Daniel', 'Nabel, Gary J.']",PLoS One,,,True
60bc864d9515f3919e673bf5eeadfbd60ef84770,PMC,Immunohistochemistry for detection of avian infectious bronchitis virus strain M41 in the proventriculus and nervous system of experimentally infected chicken embryos,http://dx.doi.org/10.1186/1743-422X-6-15,PMC2657138,19196466,CC BY,"BACKGROUND: Infectious bronchitis virus primarily induces a disease of the respiratory system, different IBV strains may show variable tissue tropisms and also affect the oviduct and the kidneys. Proventriculitis was also associated with some new IBV strains. Aim of this study was to investigate by immunohistochemistry (IHC) the tissue tropism of avian infectious bronchitis virus (IBV) strain M41 in experimentally infected chicken embryos. RESULTS: To this end chicken embryos were inoculated in the allantoic sac with 10(3 )EID(50 )of IBV M41 at 10 days of age. At 48, 72, and 120 h postinoculation (PI), embryos and chorioallantoic membranes (CAM) were sampled, fixed, and paraffin-wax embedded. Allantoic fluid was also collected and titrated in chicken embryo kidney cells (CEK). The sensitivity of IHC in detecting IBV antigens in the CAM of inoculated eggs matched the virus reisolation and detection in CEK. Using IHC, antigens of IBV were detected in nasal epithelium, trachea, lung, spleen, myocardial vasculature, liver, gastrointestinal tract, kidney, skin, sclera of the eye, spinal cord, as well as in brain neurons of the inoculated embryos. These results were consistent with virus isolation and denote the wide tissue tropism of IBV M41 in the chicken embryo. Most importantly, we found infection of vasculature and smooth muscle of the proventriculus which has not seen before with IBV strain M41. CONCLUSION: IHC can be an additional useful tool for diagnosis of IBV infection in chickens and allows further studies to foster a deeper understanding of the pathogenesis of infections with IBV strains of different virulence. Moreover, these results underline that embryonic tissues in addition to CAM could be also used as possible source to generate IBV antigens for diagnostic purposes.",2009 Feb 5,"['Abdel-Moneim, Ahmed S', 'Zlotowski, Priscila', 'Veits, Jutta', 'Keil, Günther M', 'Teifke, Jens P']",Virol J,,,True
b23a403b1daf18cd8a06665ad3111e92453bd61b,PMC,Metabolite profiling studies in Saccharomyces cerevisiae: an assisting tool to prioritize host targets for antiviral drug screening,http://dx.doi.org/10.1186/1475-2859-8-12,PMC2658664,19183481,CC BY,"BACKGROUND: The cellular proteins Pat1p, Lsm1p, and Dhh1p are required for the replication of some positive-strand viruses and therefore are potential targets for new antiviral drugs. To prioritize host targets for antiviral drug screening a comparative metabolome analysis in Saccharomyces cerevisiae reference strain BY4742 Matα his3Δ1 leu2Δ0 lys2Δ0 ura3Δ0 and deletion strains pat1Δ, lsm1Δ and dhh1Δ was performed. RESULTS: GC/MS analysis permitted the quantification of 47 polar metabolites and the identification of 41 of them. Metabolites with significant variation between the strains were identified using partial least squares to latent structures discriminate analysis (PLS-DA). The analysis revealed least differences of pat1Δ to the reference strain as characterized by Euclidian distance of normalized peak areas. The growth rate and specific production rates of ethanol and glycerol were also most similar with this strain. CONCLUSION: From these results we hypothesize that the human analog of yeast Pat1p is most likely the best drug target candidate.",2009 Jan 30,"['Schneider, Konstantin', 'Krömer, Jens Olaf', 'Wittmann, Christoph', 'Alves-Rodrigues, Isabel', 'Meyerhans, Andreas', 'Diez, Juana', 'Heinzle, Elmar']",Microb Cell Fact,,,True
5229e54b1866448ee22e138bb7c12ab67547ccac,PMC,Host-Species Transferrin Receptor 1 Orthologs Are Cellular Receptors for Nonpathogenic New World Clade B Arenaviruses,http://dx.doi.org/10.1371/journal.ppat.1000358,PMC2658809,19343214,CC0,"The ability of a New World (NW) clade B arenavirus to enter cells using human transferrin receptor 1 (TfR1) strictly correlates with its ability to cause hemorrhagic fever. Amapari (AMAV) and Tacaribe (TCRV), two nonpathogenic NW clade B arenaviruses that do not use human TfR1, are closely related to the NW arenaviruses that cause hemorrhagic fevers. Here we show that pseudotyped viruses bearing the surface glycoprotein (GP) of AMAV or TCRV can infect cells using the TfR1 orthologs of several mammalian species, including those of their respective natural hosts, the small rodent Neacomys spinosus and the fruit bat Artibeus jamaicensis. Mutation of one residue in human TfR1 makes it a functional receptor for TCRV, and mutation of four residues makes it a functional receptor for AMAV. Our data support an in vivo role for TfR1 in the replication of most, if not all, NW clade B arenaviruses, and suggest that with modest changes in their GPs the nonpathogenic arenaviruses could use human TfR1 and emerge as human pathogens.",2009 Apr 3,"['Abraham, Jonathan', 'Kwong, Jo Ann', 'Albariño, César G.', 'Lu, Jiajie G.', 'Radoshitzky, Sheli R.', 'Salazar-Bravo, Jorge', 'Farzan, Michael', 'Spiropoulou, Christina F.', 'Choe, Hyeryun']",PLoS Pathog,,,True
27869d617d1c3766400b9f33f31e28f8fb1bdbd0,PMC,Understanding Haemophilus parasuis infection in porcine spleen through a transcriptomics approach,http://dx.doi.org/10.1186/1471-2164-10-64,PMC2660370,19196461,CC BY,"BACKGROUND: Haemophilus parasuis (HPS) is an important swine pathogen that causes Glässer's disease, which is characterized by fibrinous polyserositis, meningitis and arthritis. The molecular mechanisms that underlie the pathogenesis of the disease remain poorly understood, particularly the resistance of porcine immune system to HPS invasion. In this study, we investigated the global changes in gene expression in the spleen following HPS infection using the Affymetrix Porcine Genechip™. RESULTS: A total of 931 differentially expressed (DE) transcripts were identified in the porcine spleen 7 days after HPS infection; of these, 92 unique genes showed differential expression patterns based on analysis using BLASTX and Gene Ontology. The DE genes involved in the immune response included genes for inflammasomes (RETN, S100A8, S100A9, S100A12), adhesion molecules (CLDN3, CSPG2, CD44, LGALS8), transcription factors (ZBTB16, SLC39A14, CEBPD, CEBPB), acute-phase proteins and complement (SAA1, LTF, HP, C3), differentiation genes for epithelial cells and keratinocytes (TGM1, MS4A8B, CSTA), and genes related to antigen processing and presentation (HLA-B, HLA-DRB1). Further immunostimulation analyses indicated that mRNA levels of S100A8, S100A9, and S100A12 in porcine PK-15 cells increased within 48 h and were sustained after administration of lipopolysaccharide (LPS) and Poly(I:C) respectively. In addition, mapping of DE genes to porcine health traits QTL regions showed that 70 genes were distributed in 7 different known porcine QTL regions. Finally, 10 DE genes were validated by quantitative PCR. CONCLUSION: Our findings demonstrate previously unrecognized changes in gene transcription that are associated with HPS infection in vivo, and many potential cascades identified in the study clearly merit further investigation. Our data provide new clues to the nature of the immune response in mammals, and we have identified candidate genes that are related to resistance to HPS.",2009 Feb 5,"['Chen, Hongbo', 'Li, Changchun', 'Fang, Mingdi', 'Zhu, Mengjin', 'Li, Xinyun', 'Zhou, Rui', 'Li, Kui', 'Zhao, Shuhong']",BMC Genomics,,,True
aec5514aada77bb18c23a36f314ce949ba0ff846,PMC,"""Will they just pack up and leave?"" – attitudes and intended behaviour of hospital health care workers during an influenza pandemic",http://dx.doi.org/10.1186/1472-6963-9-30,PMC2661074,19216792,CC BY,"BACKGROUND: There is a general consensus that another influenza pandemic is inevitable. Although health care workers (HCWs) are essential to the health system response, there are few studies exploring HCW attitudes to pandemic influenza. The aim of this study was to explore HCWs knowledge, attitudes and intended behaviour towards pandemic influenza. METHODS: Cross-sectional investigation of a convenience sample of clinical and non-clinical HCWs from two tertiary-referral teaching hospitals in Sydney, Australia was conducted between June 4 and October 19, 2007. The self-administered questionnaire was distributed to hospital personal from 40 different wards and departments. The main outcome measures were intentions regarding work attendance and quarantine, antiviral use and perceived preparation. RESULTS: Respondents were categorized into four main groups by occupation: Nursing (47.5%), Medical (26.0%), Allied (15.3%) and Ancillary (11.2%). Our study found that most HCWs perceived pandemic influenza to be very serious (80.9%, n = 873) but less than half were able to correctly define it (43.9%, n = 473). Only 24.8% of respondents believed their department to be prepared for a pandemic, but nonetheless most were willing to work during a pandemic if a patient or colleague had influenza. The main determinants of variation in our study were occupational factors, demographics and health beliefs. Non-clinical staff were significantly most likely to be unsure of their intentions (OR 1.43, p < 0.001). Only 42.5% (n = 459) of respondents considered that neuraminidase inhibitor antiviral medications (oseltamivir/zanamivir) would protect them against pandemic influenza, whereas 77.5% (n = 836) believed that vaccination would be of benefit. CONCLUSION: We identified two issues that could undermine the best of pandemic plans – the first, a low level of confidence in antivirals as an effective measure; secondly, that non-clinical workers are an overlooked group whose lack of knowledge and awareness could undermine pandemic plans. Other issues included a high level of confidence in dietary measures to protect against influenza, and a belief among ancillary workers that antibiotics would be protective. All health care worker strategies should include non clinical and ancillary staff to ensure adequate business continuity for hospitals. HCW education, psychosocial support and staff communication could improve knowledge of appropriate pandemic interventions and confidence in antivirals.",2009 Feb 13,"['Seale, Holly', 'Leask, Julie', 'Po, Kieren', 'MacIntyre, C Raina']",BMC Health Serv Res,,,True
2fba918741f8128e992b17b14c8a631b36801e3f,PMC,Interferon-gamma coordinates CCL3-mediated neutrophil recruitment in vivo,http://dx.doi.org/10.1186/1471-2172-10-14,PMC2662797,19298652,CC BY,"BACKGROUND: We have shown previously that acute infection with the respiratory pathogen, pneumonia virus of mice (PVM), results in local production of the proinflammatory chemokine, CCL3, and that neutrophil recruitment in response to PVM infection is reduced dramatically in CCL3 -/- mice. RESULTS: In this work, we demonstrate that CCL3-mediated neutrophil recruitment is coordinated by interferon-gamma (IFNγ). Neutrophil recruitment in response to PVM infection was diminished five-fold in IFNγ receptor gene-deleted mice, although neutrophils from IFNγR -/- mice expressed transcripts for the CCL3 receptor, CCR1 and responded functionally to CCL3 ex vivo. Similarly, in the absence of PVM infection, CCL3 overexpression alone could not elicit neutrophil recruitment in the absence of IFNγ. Interestingly, although supplemental IFNγ restored neutrophil recruitment and resulted in a sustained weight loss among CCL3-overexpressing IFNγ -/- mice, CCL3-mediated neutrophil recruitment alone did not result in the pulmonary edema or respiratory failure characteristic of severe viral infection, suggesting that CCL3 and IFN-γ together are sufficient to promote neutrophil recruitment but not pathologic activation. CONCLUSION: Our findings reveal a heretofore unrecognized hierarchical interaction between the IFNγ and CCL3, which demonstrate that IFNγ is crucial for CCL3-mediated neutrophil recruitment in vivo.",2009 Mar 19,"['Bonville, Cynthia A', 'Percopo, Caroline M', 'Dyer, Kimberly D', 'Gao, Jiliang', 'Prussin, Calman', 'Foster, Barbara', 'Rosenberg, Helene F', 'Domachowske, Joseph B']",BMC Immunol,,,True
aed44d8b5c29a7cdf02ed56dc2cbac07dd1d6eed,PMC,Hemoglobin Cleavage Site-Specificity of the Plasmodium falciparum Cysteine Proteases Falcipain-2 and Falcipain-3,http://dx.doi.org/10.1371/journal.pone.0005156,PMC2663817,19357776,CC BY,"The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 degrade host hemoglobin to provide free amino acids for parasite protein synthesis. Hemoglobin hydrolysis has been described as an ordered process initiated by aspartic proteases, but cysteine protease inhibitors completely block the process, suggesting that cysteine proteases can also initiate hemoglobin hydrolysis. To characterize the specific roles of falcipains, we used three approaches. First, using random P(1) – P(4) amino acid substrate libraries, falcipain-2 and falcipain-3 demonstrated strong preference for cleavage sites with Leu at the P(2) position. Second, with overlapping peptides spanning α and β globin and proteolysis-dependent (18)O labeling, hydrolysis was seen at many cleavage sites. Third, with intact hemoglobin, numerous cleavage products were identified. Our results suggest that hemoglobin hydrolysis by malaria parasites is not a highly ordered process, but rather proceeds with rapid cleavage by falcipains at multiple sites. However, falcipain-2 and falcipain-3 show strong specificity for P(2) Leu in small peptide substrates, in agreement with the specificity in optimized small molecule inhibitors that was identified previously. These results are consistent with a principal role of falcipain-2 and falcipain-3 in the hydrolysis of hemoglobin by P. falciparum and with the possibility of developing small molecule inhibitors with optimized specificity as antimalarial agents.",2009 Apr 9,"['Subramanian, Shoba', 'Hardt, Markus', 'Choe, Youngchool', 'Niles, Richard K.', 'Johansen, Eric B.', 'Legac, Jennifer', 'Gut, Jiri', 'Kerr, Iain D.', 'Craik, Charles S.', 'Rosenthal, Philip J.']",PLoS One,,,True
710bf21a0b14c7512f2680ba1413c518432d7278,PMC,A Novel Bocavirus Associated with Acute Gastroenteritis in Australian Children,http://dx.doi.org/10.1371/journal.ppat.1000391,PMC2663820,19381259,CC BY,"Acute gastroenteritis (AGE) is a common illness affecting all age groups worldwide, causing an estimated three million deaths annually. Viruses such as rotavirus, adenovirus, and caliciviruses are a major cause of AGE, but in many patients a causal agent cannot be found despite extensive diagnostic testing. Proposing that novel viruses are the reason for this diagnostic gap, we used molecular screening to investigate a cluster of undiagnosed cases that were part of a larger case control study into the etiology of pediatric AGE. Degenerate oligonucleotide primed (DOP) PCR was used to non-specifically amplify viral DNA from fecal specimens. The amplified DNA was then cloned and sequenced for analysis. A novel virus was detected. Elucidation and analysis of the genome indicates it is a member of the Bocavirus genus of the Parvovirinae, 23% variant at the nucleotide level from its closest formally recognized relative, the Human Bocavirus (HBoV), and similar to the very recently proposed second species of Bocavirus (HBoV2). Fecal samples collected from case control pairs during 2001 for the AGE study were tested with a bocavirus-specific PCR, and HBoV2 (sequence confirmed) was detected in 32 of 186 cases with AGE (prevalence 17.2%) compared with only 15 controls (8.1%). In this same group of children, HBoV2 prevalence was exceeded only by rotavirus (39.2%) and astrovirus (21.5%) and was more prevalent than norovirus genogroup 2 (13.4%) and adenovirus (4.8%). In a univariate analysis of the matched pairs (McNemar's Test), the odds ratio for the association of AGE with HBoV2 infection was 2.6 (95% confidence interval 1.2–5.7); P = 0.007. During the course of this screening, a second novel bocavirus was detected which we have designated HBoV species 3 (HBoV3). The prevalence of HBoV3 was low (2.7%), and it was not associated with AGE. HBoV2 and HBoV3 are newly discovered bocaviruses, of which HBoV2 is the thirdmost-prevalent virus, after rotavirus and astrovirus, associated with pediatric AGE in this study.",2009 Apr 17,"['Arthur, Jane L.', 'Higgins, Geoffrey D.', 'Davidson, Geoffrey P.', 'Givney, Rodney C.', 'Ratcliff, Rodney M.']",PLoS Pathog,,,True
1eef10e356884a9f63b17f13df74ac185700ab06,PMC,What can health care professionals in the United Kingdom learn from Malawi?,http://dx.doi.org/10.1186/1478-4491-7-26,PMC2666626,19327137,CC BY,"Debate on how resource-rich countries and their health care professionals should help the plight of sub-Saharan Africa appears locked in a mind-set dominated by gloomy statistics and one-way monetary aid. Having established a project to link primary care clinics based on two-way sharing of education rather than one-way aid, our United Kingdom colleagues often ask us: ""But what can we learn from Malawi?"" A recent fact-finding visit to Malawi helped us clarify some aspects of health care that may be of relevance to health care professionals in the developed world, including the United Kingdom. This commentary article is focused on encouraging debate and discussion as to how we might wish to re-think our relationship with colleagues in other health care environments and consider how we can work together on a theme of two-way shared learning rather than one-way aid.",2009 Mar 27,"['Neville, Ron', 'Neville, Jemma']",Hum Resour Health,,,True
cdbdc0b6176729a11ba5e08c708408592d189657,PMC,Spatial analysis of falls in an urban community of Hong Kong,http://dx.doi.org/10.1186/1476-072X-8-14,PMC2666650,19291326,CC BY,"BACKGROUND: Falls are an issue of great public health concern. This study focuses on outdoor falls within an urban community in Hong Kong. Urban environmental hazards are often place-specific and dependent upon the built features, landscape characteristics, and habitual activities. Therefore, falls must be examined with respect to local situations. RESULTS: This paper uses spatial analysis methods to map fall occurrences and examine possible environmental attributes of falls in an urban community of Hong Kong. The Nearest neighbour hierarchical (Nnh) and Standard Deviational Ellipse (SDE) techniques can offer additional insights about the circumstances and environmental factors that contribute to falls. The results affirm the multi-factorial nature of falls at specific locations and for selected groups of the population. CONCLUSION: The techniques to detect hot spots of falls yield meaningful results that enable the identification of high risk locations. The combined use of descriptive and spatial analyses can be beneficial to policy makers because different preventive measures can be devised based on the types of environmental risk factors identified. The analyses are also important preludes to establishing research hypotheses for more focused studies.",2009 Mar 17,"['Lai, Poh C', 'Low, Chien T', 'Wong, Martin', 'Wong, Wing C', 'Chan, Ming H']",Int J Health Geogr,,,True
844b876f1636f5d031fe856cd7a63ae5f5c11fe7,PMC,The impact of surfactant protein-A on ozone-induced changes in the mouse bronchoalveolar lavage proteome,http://dx.doi.org/10.1186/1477-5956-7-12,PMC2666657,19323824,CC BY,"BACKGROUND: Ozone is a major component of air pollution. Exposure to this powerful oxidizing agent can cause or exacerbate many lung conditions, especially those involving innate immunity. Surfactant protein-A (SP-A) plays many roles in innate immunity by participating directly in host defense as it exerts opsonin function, or indirectly via its ability to regulate alveolar macrophages and other innate immune cells. The mechanism(s) responsible for ozone-induced pathophysiology, while likely related to oxidative stress, are not well understood. METHODS: We employed 2-dimensional difference gel electrophoresis (2D-DIGE), a discovery proteomics approach, coupled with MALDI-ToF/ToF to compare the bronchoalveolar lavage (BAL) proteomes in wild type (WT) and SP-A knockout (KO) mice and to assess the impact of ozone or filtered air on the expression of BAL proteins. Using the PANTHER database and the published literature most identified proteins were placed into three functional groups. RESULTS: We identified 66 proteins and focused our analysis on these proteins. Many of them fell into three categories: defense and immunity; redox regulation; and protein metabolism, modification and chaperones. In response to the oxidative stress of acute ozone exposure (2 ppm; 3 hours) there were many significant changes in levels of expression of proteins in these groups. Most of the proteins in the redox group were decreased, the proteins involved in protein metabolism increased, and roughly equal numbers of increases and decreases were seen in the defense and immunity group. Responses between WT and KO mice were similar in many respects. However, the percent change was consistently greater in the KO mice and there were more changes that achieved statistical significance in the KO mice, with levels of expression in filtered air-exposed KO mice being closer to ozone-exposed WT mice than to filtered air-exposed WT mice. CONCLUSION: We postulate that SP-A plays a role in reactive oxidant scavenging in WT mice and that its absence in the KO mice in the presence or absence of ozone exposure results in more pronounced, and presumably chronic, oxidative stress.",2009 Mar 26,"['Haque, Rizwanul', 'Umstead, Todd M', 'Freeman, Willard M', 'Floros, Joanna', 'Phelps, David S']",Proteome Sci,,,True
58ebd3ddb3543355def684c9762e4e24388c61bb,PMC,Which preventive measures might protect health care workers from SARS?,http://dx.doi.org/10.1186/1471-2458-9-81,PMC2666722,19284644,CC BY,"BACKGROUND: Despite the use of a series of preventive measures, a high incidence of severe acute respiratory syndrome (SARS) was observed among health care workers (HCWs) during the SARS epidemic. This study aimed to determine which preventive measures may have been effective in protecting HCWs from infection, and which were not effective. METHODS: A retrospective study was performed among 758 'frontline' health care workers who cared for SARS patients at the Second Affiliated Hospital and the Third Affiliated Hospital of Sun Yat-sen University. The HCWs with IgG against SARS and those without IgG against SARS were respectively defined as the ""case group"" and the ""control group"", and logistic regression was conducted to explore the risk factors for SARS infection in HCWs. RESULTS: After adjusting for age, gender, marital status, educational level, professional title, and the department in which an individual worked, the results of a multivariate logistic regression analysis indicated that incidence of SARS among HCWs was significantly and positively associated with: performing tracheal intubations for SARS patients, methods used for air ventilation in wards, avoiding face-to-face interaction with SARS patients, the number of pairs of gloves worn by HCWs, and caring for serious SARS cases. CONCLUSION: Some measures, particularly good air ventilation in SARS wards, may be effective in minimizing or preventing SARS transmission among HCWs in hospitals.",2009 Mar 13,"['Chen, Wei-Qing', 'Ling, Wen-Hua', 'Lu, Ci-Yong', 'Hao, Yuan-Tao', 'Lin, Zhong-Ning', 'Ling, Li', 'Huang, Jian', 'Li, Gang', 'Yan, Guang-Mei']",BMC Public Health,,,True
aea331cddd5eef46512ecea34503ed02af95d23e,PMC,Proteolytic processing of a precursor protein for a growth-promoting peptide by a subtilisin serine protease in Arabidopsis,http://dx.doi.org/10.1111/j.1365-313X.2008.03598.x,PMC2667306,18643977,CC BY,"Phytosulfokines (PSKs) are secreted, sulfated peptide hormones derived from larger prepropeptide precursors. Proteolytic processing of one of the precursors, AtPSK4, was demonstrated by cleavage of a preproAtPSK4–myc transgene product to AtPSK4–myc. Cleavage of proAtPSK4 was induced by placing root explants in tissue culture. The processing of proAtPSK4 was dependent on AtSBT1.1, a subtilisin-like serine protease, encoded by one of 56 subtilase genes in Arabidopsis. The gene encoding AtSBT1.1 was up-regulated following the transfer of root explants to tissue culture, suggesting that activation of the proteolytic machinery that cleaves proAtPSK4 is dependent on AtSBT1.1 expression. We also demonstrated that a fluorogenic peptide representing the putative subtilase recognition site in proAtPSK4 is cleaved in vitro by affinity-purified AtSBT1.1. An alanine scan through the recognition site peptide indicated that AtSBT1.1 is fairly specific for the AtPSK4 precursor. Thus, this peptide growth factor, which promotes callus formation in culture, is proteolytically cleaved from its precursor by a specific plant subtilase encoded by a gene that is up-regulated during the process of transfering root explants to tissue culture.",2008 Oct 1,"['Srivastava, Renu', 'Liu, Jian-Xiang', 'Howell, Stephen H']",Plant J,,,True
e0eb2e56b8dcac84960183ca6af7a43130064de4,PMC,Proteolytic processing of a precursor protein for a growth-promoting peptide by a subtilisin serine protease in Arabidopsis,http://dx.doi.org/10.1111/j.1365-313X.2008.03598.x,PMC2667306,18643977,CC BY,"Phytosulfokines (PSKs) are secreted, sulfated peptide hormones derived from larger prepropeptide precursors. Proteolytic processing of one of the precursors, AtPSK4, was demonstrated by cleavage of a preproAtPSK4–myc transgene product to AtPSK4–myc. Cleavage of proAtPSK4 was induced by placing root explants in tissue culture. The processing of proAtPSK4 was dependent on AtSBT1.1, a subtilisin-like serine protease, encoded by one of 56 subtilase genes in Arabidopsis. The gene encoding AtSBT1.1 was up-regulated following the transfer of root explants to tissue culture, suggesting that activation of the proteolytic machinery that cleaves proAtPSK4 is dependent on AtSBT1.1 expression. We also demonstrated that a fluorogenic peptide representing the putative subtilase recognition site in proAtPSK4 is cleaved in vitro by affinity-purified AtSBT1.1. An alanine scan through the recognition site peptide indicated that AtSBT1.1 is fairly specific for the AtPSK4 precursor. Thus, this peptide growth factor, which promotes callus formation in culture, is proteolytically cleaved from its precursor by a specific plant subtilase encoded by a gene that is up-regulated during the process of transfering root explants to tissue culture.",2008 Oct 1,"['Srivastava, Renu', 'Liu, Jian-Xiang', 'Howell, Stephen H']",Plant J,,,False
bd0a970593b33e212262cce0e5a9be28b555f18e,PMC,Conducting Research in Disease Outbreaks,http://dx.doi.org/10.1371/journal.pntd.0000335,PMC2669128,19399167,CC BY,,2009 Apr 28,"['Macklin, Ruth', 'Cowan, Ethan']",PLoS Negl Trop Dis,,,True
bc4e3f1afdbc64641df9ffa7707910d13014d529,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,True
38f132558364bdc7b9d8c509641d8aa15cfc6e62,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,False
898b2d11e25f2f6ccc7dab4b572f6c6f0628639f,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,False
ca5f8c2caf2ab03fcb4a59770cf9f319d87123ea,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,False
225a753b7007314d6d5c1afd339b30d032f33c7d,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,False
794abd55244633dadcc6a225ff7c8f0d551e3a66,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,False
24cd9a024288d5259cb0a8d140efa70a25f73bc0,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,False
59e9689301d4f10b7d2d5cc6d183ec23afcfcc98,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,False
854484745a732a6229fe917030fd35198ffac799,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,False
bd55c44a2d6e3ec7d067fd6c46d569e4cc869d70,PMC,Quarantine for pandemic influenza control at the borders of small island nations,http://dx.doi.org/10.1186/1471-2334-9-27,PMC2670846,19284571,CC BY,"BACKGROUND: Although border quarantine is included in many influenza pandemic plans, detailed guidelines have yet to be formulated, including considerations for the optimal quarantine length. Motivated by the situation of small island nations, which will probably experience the introduction of pandemic influenza via just one airport, we examined the potential effectiveness of quarantine as a border control measure. METHODS: Analysing the detailed epidemiologic characteristics of influenza, the effectiveness of quarantine at the borders of islands was modelled as the relative reduction of the risk of releasing infectious individuals into the community, explicitly accounting for the presence of asymptomatic infected individuals. The potential benefit of adding the use of rapid diagnostic testing to the quarantine process was also considered. RESULTS: We predict that 95% and 99% effectiveness in preventing the release of infectious individuals into the community could be achieved with quarantine periods of longer than 4.7 and 8.6 days, respectively. If rapid diagnostic testing is combined with quarantine, the lengths of quarantine to achieve 95% and 99% effectiveness could be shortened to 2.6 and 5.7 days, respectively. Sensitivity analysis revealed that quarantine alone for 8.7 days or quarantine for 5.7 days combined with using rapid diagnostic testing could prevent secondary transmissions caused by the released infectious individuals for a plausible range of prevalence at the source country (up to 10%) and for a modest number of incoming travellers (up to 8000 individuals). CONCLUSION: Quarantine at the borders of island nations could contribute substantially to preventing the arrival of pandemic influenza (or at least delaying the arrival date). For small island nations we recommend consideration of quarantine alone for 9 days or quarantine for 6 days combined with using rapid diagnostic testing (if available).",2009 Mar 11,"['Nishiura, Hiroshi', 'Wilson, Nick', 'Baker, Michael G']",BMC Infect Dis,,,True
74f823e968a2920c96c87977da7289f5363979da,PMC,Molecular Mechanisms of Recombination Restriction in the Envelope Gene of the Human Immunodeficiency Virus,http://dx.doi.org/10.1371/journal.ppat.1000418,PMC2671596,19424420,CC BY,"The ability of pathogens to escape the host's immune response is crucial for the establishment of persistent infections and can influence virulence. Recombination has been observed to contribute to this process by generating novel genetic variants. Although distinctive recombination patterns have been described in many viral pathogens, little is known about the influence of biases in the recombination process itself relative to selective forces acting on newly formed recombinants. Understanding these influences is important for determining how recombination contributes to pathogen genome and proteome evolution. Most previous research on recombination-driven protein evolution has focused on relatively simple proteins, usually in the context of directed evolution experiments. Here, we study recombination in the envelope gene of HIV-1 between primary isolates belonging to subtypes that recombine naturally in the HIV/AIDS pandemic. By characterizing the early steps in the generation of recombinants, we provide novel insights into the evolutionary forces that shape recombination patterns within viral populations. Specifically, we show that the combined effects of mechanistic processes that determine the locations of recombination breakpoints across the HIV-1 envelope gene, and purifying selection acting against dysfunctional recombinants, can explain almost the entire distribution of breakpoints found within this gene in nature. These constraints account for the surprising paucity of recombination breakpoints found in infected individuals within this highly variable gene. Thus, the apparent randomness of HIV evolution via recombination may in fact be relatively more predictable than anticipated. In addition, the dominance of purifying selection in localized areas of the HIV genome defines regions where functional constraints on recombinants appear particularly strong, pointing to vulnerable aspects of HIV biology.",2009 May 8,"['Simon-Loriere, Etienne', 'Galetto, Roman', 'Hamoudi, Meriem', 'Archer, John', 'Lefeuvre, Pierre', 'Martin, Darren P.', 'Robertson, David L.', 'Negroni, Matteo']",PLoS Pathog,,,True
cf0dd4d9f9f906626d5bc4a01e1f1eb21806291c,PMC,Strengthening field-based training in low and middle-income countries to build public health capacity: Lessons from Australia's Master of Applied Epidemiology program,http://dx.doi.org/10.1186/1743-8462-6-5,PMC2672090,19358710,CC BY,"BACKGROUND: The International Health Regulations (2005) and the emergence and global spread of infectious diseases have triggered a re-assessment of how rich countries should support capacity development for communicable disease control in low and medium income countries (LMIC). In LMIC, three types of public health training have been tried: the university-based model; streamed training for specialised workers; and field-based programs. The first has low rates of production and teaching may not always be based on the needs and priorities of the host country. The second model is efficient, but does not accord the workers sufficient status to enable them to impact on policy. The third has the most potential as a capacity development measure for LMIC, but in practice faces challenges which may limit its ability to promote capacity development. DISCUSSION: We describe Australia's first Master of Applied Epidemiology (MAE) model (established in 1991), which uses field-based training to strengthen the control of communicable diseases. A central attribute of this model is the way it partners and complements health department initiatives to enhance workforce skills, health system performance and the evidence-base for policies, programs and practice. SUMMARY: The MAE experience throws light on ways Australia could collaborate in regional capacity development initiatives. Key needs are a shared vision for a regional approach to integrate training with initiatives that strengthen service and research, and the pooling of human, financial and technical resources. We focus on communicable diseases, but our findings and recommendations are generalisable to other areas of public health.",2009 Apr 9,"['Patel, Mahomed S', 'Phillips, Christine B']",Aust New Zealand Health Policy,,,True
0162b627476379a84d5a92480a881efdd3063f66,PMC,Avian Influenza Virus Glycoproteins Restrict Virus Replication and Spread through Human Airway Epithelium at Temperatures of the Proximal Airways,http://dx.doi.org/10.1371/journal.ppat.1000424,PMC2673688,19436701,CC0,"Transmission of avian influenza viruses from bird to human is a rare event even though avian influenza viruses infect the ciliated epithelium of human airways in vitro and ex vivo. Using an in vitro model of human ciliated airway epithelium (HAE), we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37°C), avian, but not human, influenza viruses are restricted for infection at the cooler temperatures of the human proximal airways (32°C). These data support the hypothesis that avian influenza viruses, ordinarily adapted to the temperature of the avian enteric tract (40°C), rarely infect humans, in part due to differences in host airway regional temperatures. Previously, a critical residue at position 627 in the avian influenza virus polymerase subunit, PB2, was identified as conferring temperature-dependency in mammalian cells. Here, we use reverse genetics to show that avianization of residue 627 attenuates a human virus, but does not account for the different infection between 32°C and 37°C. To determine the mechanism of temperature restriction of avian influenza viruses in HAE at 32°C, we generated recombinant human influenza viruses in either the A/Victoria/3/75 (H3N2) or A/PR/8/34 (H1N1) genetic background that contained avian or avian-like glycoproteins. Two of these viruses, A/Victoria/3/75 with L226Q and S228G mutations in hemagglutinin (HA) and neuraminidase (NA) from A/Chick/Italy/1347/99 and A/PR/8/34 containing the H7 and N1 from A/Chick/Italy/1347/99, exhibited temperature restriction approaching that of wholly avian influenza viruses. These data suggest that influenza viruses bearing avian or avian-like surface glycoproteins have a reduced capacity to establish productive infection at the temperature of the human proximal airways. This temperature restriction may limit zoonotic transmission of avian influenza viruses and suggests that adaptation of avian influenza viruses to efficient infection at 32°C may represent a critical evolutionary step enabling human-to-human transmission.",2009 May 15,"['Scull, Margaret A.', 'Gillim-Ross, Laura', 'Santos, Celia', 'Roberts, Kim L.', 'Bordonali, Elena', 'Subbarao, Kanta', 'Barclay, Wendy S.', 'Pickles, Raymond J.']",PLoS Pathog,,,True
3f962f74bcf72c06a4f0941b8da40742024dae3f,PMC,The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes,http://dx.doi.org/10.1371/journal.ppat.1000428,PMC2674928,19436709,CC BY,"Since the outbreak of severe acute respiratory syndrome (SARS) in 2003, the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus (SARS-CoV), the non-structural proteins (Nsps), have been determined. However, within the large Nsp3 (1922 amino-acid residues), the structure and function of the so-called SARS-unique domain (SUD) have remained elusive. SUD occurs only in SARS-CoV and the highly related viruses found in certain bats, but is absent from all other coronaviruses. Therefore, it has been speculated that it may be involved in the extreme pathogenicity of SARS-CoV, compared to other coronaviruses, most of which cause only mild infections in humans. In order to help elucidate the function of the SUD, we have determined crystal structures of fragment 389–652 (“SUD(core)”) of Nsp3, which comprises 264 of the 338 residues of the domain. Both the monoclinic and triclinic crystal forms (2.2 and 2.8 Å resolution, respectively) revealed that SUD(core) forms a homodimer. Each monomer consists of two subdomains, SUD-N and SUD-M, with a macrodomain fold similar to the SARS-CoV X-domain. However, in contrast to the latter, SUD fails to bind ADP-ribose, as determined by zone-interference gel electrophoresis. Instead, the entire SUD(core) as well as its individual subdomains interact with oligonucleotides known to form G-quadruplexes. This includes oligodeoxy- as well as oligoribonucleotides. Mutations of selected lysine residues on the surface of the SUD-N subdomain lead to reduction of G-quadruplex binding, whereas mutations in the SUD-M subdomain abolish it. As there is no evidence for Nsp3 entering the nucleus of the host cell, the SARS-CoV genomic RNA or host-cell mRNA containing long G-stretches may be targets of SUD. The SARS-CoV genome is devoid of G-stretches longer than 5–6 nucleotides, but more extended G-stretches are found in the 3′-nontranslated regions of mRNAs coding for certain host-cell proteins involved in apoptosis or signal transduction, and have been shown to bind to SUD in vitro. Therefore, SUD may be involved in controlling the host cell's response to the viral infection. Possible interference with poly(ADP-ribose) polymerase-like domains is also discussed.",2009 May 15,"['Tan, Jinzhi', 'Vonrhein, Clemens', 'Smart, Oliver S.', 'Bricogne, Gerard', 'Bollati, Michela', 'Kusov, Yuri', 'Hansen, Guido', 'Mesters, Jeroen R.', 'Schmidt, Christian L.', 'Hilgenfeld, Rolf']",PLoS Pathog,,,True
cfd27fc9582d326ef3b09be615d649e3b6e85c61,PMC,The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes,http://dx.doi.org/10.1371/journal.ppat.1000428,PMC2674928,19436709,CC BY,"Since the outbreak of severe acute respiratory syndrome (SARS) in 2003, the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus (SARS-CoV), the non-structural proteins (Nsps), have been determined. However, within the large Nsp3 (1922 amino-acid residues), the structure and function of the so-called SARS-unique domain (SUD) have remained elusive. SUD occurs only in SARS-CoV and the highly related viruses found in certain bats, but is absent from all other coronaviruses. Therefore, it has been speculated that it may be involved in the extreme pathogenicity of SARS-CoV, compared to other coronaviruses, most of which cause only mild infections in humans. In order to help elucidate the function of the SUD, we have determined crystal structures of fragment 389–652 (“SUD(core)”) of Nsp3, which comprises 264 of the 338 residues of the domain. Both the monoclinic and triclinic crystal forms (2.2 and 2.8 Å resolution, respectively) revealed that SUD(core) forms a homodimer. Each monomer consists of two subdomains, SUD-N and SUD-M, with a macrodomain fold similar to the SARS-CoV X-domain. However, in contrast to the latter, SUD fails to bind ADP-ribose, as determined by zone-interference gel electrophoresis. Instead, the entire SUD(core) as well as its individual subdomains interact with oligonucleotides known to form G-quadruplexes. This includes oligodeoxy- as well as oligoribonucleotides. Mutations of selected lysine residues on the surface of the SUD-N subdomain lead to reduction of G-quadruplex binding, whereas mutations in the SUD-M subdomain abolish it. As there is no evidence for Nsp3 entering the nucleus of the host cell, the SARS-CoV genomic RNA or host-cell mRNA containing long G-stretches may be targets of SUD. The SARS-CoV genome is devoid of G-stretches longer than 5–6 nucleotides, but more extended G-stretches are found in the 3′-nontranslated regions of mRNAs coding for certain host-cell proteins involved in apoptosis or signal transduction, and have been shown to bind to SUD in vitro. Therefore, SUD may be involved in controlling the host cell's response to the viral infection. Possible interference with poly(ADP-ribose) polymerase-like domains is also discussed.",2009 May 15,"['Tan, Jinzhi', 'Vonrhein, Clemens', 'Smart, Oliver S.', 'Bricogne, Gerard', 'Bollati, Michela', 'Kusov, Yuri', 'Hansen, Guido', 'Mesters, Jeroen R.', 'Schmidt, Christian L.', 'Hilgenfeld, Rolf']",PLoS Pathog,,,False
1560867701aecc60f73407501a5c5c85e53c8522,PMC,MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins,http://dx.doi.org/10.1371/journal.pone.0005466,PMC2674933,19404494,CC BY,"BACKGROUND: Host responses to viral infection include both immune activation and programmed cell death. The mitochondrial antiviral signaling adaptor, MAVS (IPS-1, VISA or Cardif) is critical for host defenses to viral infection by inducing type-1 interferons (IFN-I), however its role in virus-induced apoptotic responses has not been elucidated. PRINCIPAL FINDINGS: We show that MAVS causes apoptosis independent of its function in initiating IFN-I production. MAVS-induced cell death requires mitochondrial localization, is caspase dependent, and displays hallmarks of apoptosis. Furthermore, MAVS(−/−) fibroblasts are resistant to Sendai virus-induced apoptosis. A functional screen identifies the hepatitis C virus NS3/4A and the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) nonstructural protein (NSP15) as inhibitors of MAVS-induced apoptosis, possibly as a method of immune evasion. SIGNIFICANCE: This study describes a novel role for MAVS in controlling viral infections through the induction of apoptosis, and identifies viral proteins which inhibit this host response.",2009 Mar 7,"['Lei, Yu', 'Moore, Chris B.', 'Liesman, Rachael M.', ""O'Connor, Brian P."", 'Bergstralh, Daniel T.', 'Chen, Zhijian J.', 'Pickles, Raymond J.', 'Ting, Jenny P.-Y.']",PLoS One,,,True
5f8d96a8606eb6c9a89a1160f8b498c6c0efecba,PMC,Targeted Strategies for Henipavirus Therapeutics,http://dx.doi.org/10.2174/1874357900701010014,PMC2675550,19440455,CC BY,"Hendra and Nipah viruses are related emergent paramyxoviruses that infect and cause disease in animals and humans. Disease manifests as a generalized vasculitis affecting multiple organs, but is the most severe in the respiratory and central nervous systems. The high case fatality and person-to-person transmission associated with the most recent NiV outbreaks, and the recent re-emergence of HeV, emphasize the importance and necessity of effective therapeutics for these novel agents. In recent years henipavirus research has revealed a more complete understanding of pathogenesis and, as a consequence, viable approaches towards vaccines and therapeutics have emerged. All strategies target early steps in viral replication including receptor binding and membrane fusion. Animal models have been developed, some of which may prove more valuable than others for evaluating the efficacy of therapeutic agents and regimes. Assessments of protective host immunity and drug pharmacokinetics will be crucial to the further advancement of therapeutic compounds.",2007 Sep 28,"['Bossart, Katharine N', 'Bingham, John', 'Middleton, Deborah']",Open Virol J,,,True
9179c5c9df6bf1ac1aab2f413d18c1954e680fd2,PMC,Differential stepwise evolution of SARS coronavirus functional proteins in different host species,http://dx.doi.org/10.1186/1471-2148-9-52,PMC2676248,19261195,CC BY,"BACKGROUND: SARS coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and extensive investigations indicated that it originated from an animal source (probably bats) and was recently introduced into the human population via wildlife animals from wet markets in southern China. Previous studies revealed that the spike (S) protein of SARS had experienced adaptive evolution, but whether other functional proteins of SARS have undergone adaptive evolution is not known. RESULTS: We employed several methods to investigate selective pressure among different SARS-CoV groups representing different epidemic periods and hosts. Our results suggest that most functional proteins of SARS-CoV have experienced a stepwise adaptive evolutionary pathway. Similar to previous studies, the spike protein underwent strong positive selection in the early and middle phases, and became stabilized in the late phase. In addition, the replicase experienced positive selection only in human patients, whereas assembly proteins experienced positive selection mainly in the middle and late phases. No positive selection was found in any proteins of bat SARS-like-CoV. Furthermore, specific amino acid sites that may be the targets of positive selection in each group are identified. CONCLUSION: This extensive evolutionary analysis revealed the stepwise evolution of different functional proteins of SARS-CoVs at different epidemic stages and different hosts. These results support the hypothesis that SARS-CoV originated from bats and that the spill over into civets and humans were more recent events.",2009 Mar 5,"['Tang, Xianchun', 'Li, Gang', 'Vasilakis, Nikos', 'Zhang, Yuan', 'Shi, Zhengli', 'Zhong, Yang', 'Wang, Lin-Fa', 'Zhang, Shuyi']",BMC Evol Biol,,,True
c2a6c7620806625deff2f67d0b5924ac1c52499e,PMC,Differential stepwise evolution of SARS coronavirus functional proteins in different host species,http://dx.doi.org/10.1186/1471-2148-9-52,PMC2676248,19261195,CC BY,"BACKGROUND: SARS coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and extensive investigations indicated that it originated from an animal source (probably bats) and was recently introduced into the human population via wildlife animals from wet markets in southern China. Previous studies revealed that the spike (S) protein of SARS had experienced adaptive evolution, but whether other functional proteins of SARS have undergone adaptive evolution is not known. RESULTS: We employed several methods to investigate selective pressure among different SARS-CoV groups representing different epidemic periods and hosts. Our results suggest that most functional proteins of SARS-CoV have experienced a stepwise adaptive evolutionary pathway. Similar to previous studies, the spike protein underwent strong positive selection in the early and middle phases, and became stabilized in the late phase. In addition, the replicase experienced positive selection only in human patients, whereas assembly proteins experienced positive selection mainly in the middle and late phases. No positive selection was found in any proteins of bat SARS-like-CoV. Furthermore, specific amino acid sites that may be the targets of positive selection in each group are identified. CONCLUSION: This extensive evolutionary analysis revealed the stepwise evolution of different functional proteins of SARS-CoVs at different epidemic stages and different hosts. These results support the hypothesis that SARS-CoV originated from bats and that the spill over into civets and humans were more recent events.",2009 Mar 5,"['Tang, Xianchun', 'Li, Gang', 'Vasilakis, Nikos', 'Zhang, Yuan', 'Shi, Zhengli', 'Zhong, Yang', 'Wang, Lin-Fa', 'Zhang, Shuyi']",BMC Evol Biol,,,False
9d811a663f9c0c0eb76946d3dd7d11369ce5ef2a,PMC,Differential stepwise evolution of SARS coronavirus functional proteins in different host species,http://dx.doi.org/10.1186/1471-2148-9-52,PMC2676248,19261195,CC BY,"BACKGROUND: SARS coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and extensive investigations indicated that it originated from an animal source (probably bats) and was recently introduced into the human population via wildlife animals from wet markets in southern China. Previous studies revealed that the spike (S) protein of SARS had experienced adaptive evolution, but whether other functional proteins of SARS have undergone adaptive evolution is not known. RESULTS: We employed several methods to investigate selective pressure among different SARS-CoV groups representing different epidemic periods and hosts. Our results suggest that most functional proteins of SARS-CoV have experienced a stepwise adaptive evolutionary pathway. Similar to previous studies, the spike protein underwent strong positive selection in the early and middle phases, and became stabilized in the late phase. In addition, the replicase experienced positive selection only in human patients, whereas assembly proteins experienced positive selection mainly in the middle and late phases. No positive selection was found in any proteins of bat SARS-like-CoV. Furthermore, specific amino acid sites that may be the targets of positive selection in each group are identified. CONCLUSION: This extensive evolutionary analysis revealed the stepwise evolution of different functional proteins of SARS-CoVs at different epidemic stages and different hosts. These results support the hypothesis that SARS-CoV originated from bats and that the spill over into civets and humans were more recent events.",2009 Mar 5,"['Tang, Xianchun', 'Li, Gang', 'Vasilakis, Nikos', 'Zhang, Yuan', 'Shi, Zhengli', 'Zhong, Yang', 'Wang, Lin-Fa', 'Zhang, Shuyi']",BMC Evol Biol,,,False
22351fd6861be2afb9543f84031ac903e22dd0bb,PMC,Differential stepwise evolution of SARS coronavirus functional proteins in different host species,http://dx.doi.org/10.1186/1471-2148-9-52,PMC2676248,19261195,CC BY,"BACKGROUND: SARS coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and extensive investigations indicated that it originated from an animal source (probably bats) and was recently introduced into the human population via wildlife animals from wet markets in southern China. Previous studies revealed that the spike (S) protein of SARS had experienced adaptive evolution, but whether other functional proteins of SARS have undergone adaptive evolution is not known. RESULTS: We employed several methods to investigate selective pressure among different SARS-CoV groups representing different epidemic periods and hosts. Our results suggest that most functional proteins of SARS-CoV have experienced a stepwise adaptive evolutionary pathway. Similar to previous studies, the spike protein underwent strong positive selection in the early and middle phases, and became stabilized in the late phase. In addition, the replicase experienced positive selection only in human patients, whereas assembly proteins experienced positive selection mainly in the middle and late phases. No positive selection was found in any proteins of bat SARS-like-CoV. Furthermore, specific amino acid sites that may be the targets of positive selection in each group are identified. CONCLUSION: This extensive evolutionary analysis revealed the stepwise evolution of different functional proteins of SARS-CoVs at different epidemic stages and different hosts. These results support the hypothesis that SARS-CoV originated from bats and that the spill over into civets and humans were more recent events.",2009 Mar 5,"['Tang, Xianchun', 'Li, Gang', 'Vasilakis, Nikos', 'Zhang, Yuan', 'Shi, Zhengli', 'Zhong, Yang', 'Wang, Lin-Fa', 'Zhang, Shuyi']",BMC Evol Biol,,,False
61f80012b6b8ea03a65fe97eefc30480990b11be,PMC,P58(IPK): A Novel “CIHD” Member of the Host Innate Defense Response against Pathogenic Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1000438,PMC2677460,19461876,CC0,"To support their replication, viruses take advantage of numerous cellular factors and processes. Recent large-scale screens have identified hundreds of such factors, yet little is known about how viruses exploit any of these. Influenza virus infection post-translationally activates P58(IPK), a cellular inhibitor of the interferon-induced, dsRNA-activated eIF2α kinase, PKR. Here, we report that infection of P58(IPK) knockout mice with influenza virus resulted in increased lung pathology, immune cell apoptosis, PKR activation, and mortality. Analysis of lung transcriptional profiles, including those induced by the reconstructed 1918 pandemic virus, revealed increased expression of genes associated with the cell death, immune, and inflammatory responses. These experiments represent the first use of a mammalian infection model to demonstrate the role of P58(IPK) in the antiviral response. Our results suggest that P58(IPK) represents a new class of molecule, a cellular inhibitor of the host defense (CIHD), as P58(IPK) is activated during virus infection to inhibit virus-induced apoptosis and inflammation to prolong host survival, even while prolonging viral replication.",2009 May 22,"['Goodman, Alan G.', 'Fornek, Jamie L.', 'Medigeshi, Guruprasad R.', 'Perrone, Lucy A.', 'Peng, Xinxia', 'Dyer, Matthew D.', 'Proll, Sean C.', 'Knoblaugh, Sue E.', 'Carter, Victoria S.', 'Korth, Marcus J.', 'Nelson, Jay A.', 'Tumpey, Terrence M.', 'Katze, Michael G.']",PLoS Pathog,,,True
61f7459a82d39c89e72c2c8068dbb87f7652dba9,PMC,Acclimatory responses of the Daphnia pulex proteome to environmental changes. II. Chronic exposure to different temperatures (10 and 20°C) mainly affects protein metabolism,http://dx.doi.org/10.1186/1472-6793-9-8,PMC2678069,19383147,CC BY,"BACKGROUND: Temperature affects essentially every aspect of the biology of poikilothermic animals including the energy and mass budgets, activity, growth, and reproduction. While thermal effects in ecologically important groups such as daphnids have been intensively studied at the ecosystem level and at least partly at the organismic level, much less is known about the molecular mechanisms underlying the acclimation to different temperatures. By using 2D gel electrophoresis and mass spectrometry, the present study identified the major elements of the temperature-induced subset of the proteome from differently acclimated Daphnia pulex. RESULTS: Specific sets of proteins were found to be differentially expressed in 10°C or 20°C acclimated D. pulex. Most cold-repressed proteins comprised secretory enzymes which are involved in protein digestion (trypsins, chymotrypsins, astacin, carboxypeptidases). The cold-induced sets of proteins included several vitellogenin and actin isoforms (cytoplasmic and muscle-specific), and an AAA+ ATPase. Carbohydrate-modifying enzymes were constitutively expressed or down-regulated in the cold. CONCLUSION: Specific sets of cold-repressed and cold-induced proteins in D. pulex can be related to changes in the cellular demand for amino acids or to the compensatory control of physiological processes. The increase of proteolytic enzyme concentration and the decrease of vitellogenin, actin and total protein concentration between 10°C and 20°C acclimated animals reflect the increased amino-acids demand and the reduced protein reserves in the animal's body. Conversely, the increase of actin concentration in cold-acclimated animals may contribute to a compensatory mechanism which ensures the relative constancy of muscular performance. The sheer number of peptidase genes (serine-peptidase-like: > 200, astacin-like: 36, carboxypeptidase-like: 30) in the D. pulex genome suggests large-scaled gene family expansions that might reflect specific adaptations to the lifestyle of a planktonic filter feeder in a highly variable aquatic environment.",2009 Apr 21,"['Schwerin, Susanne', 'Zeis, Bettina', 'Lamkemeyer, Tobias', 'Paul, Rüdiger J', 'Koch, Marita', 'Madlung, Johannes', 'Fladerer, Claudia', 'Pirow, Ralph']",BMC Physiol,,,True
faef77dd02384453eb8aef0159dc8bf52499a071,PMC,Acclimatory responses of the Daphnia pulex proteome to environmental changes. II. Chronic exposure to different temperatures (10 and 20°C) mainly affects protein metabolism,http://dx.doi.org/10.1186/1472-6793-9-8,PMC2678069,19383147,CC BY,"BACKGROUND: Temperature affects essentially every aspect of the biology of poikilothermic animals including the energy and mass budgets, activity, growth, and reproduction. While thermal effects in ecologically important groups such as daphnids have been intensively studied at the ecosystem level and at least partly at the organismic level, much less is known about the molecular mechanisms underlying the acclimation to different temperatures. By using 2D gel electrophoresis and mass spectrometry, the present study identified the major elements of the temperature-induced subset of the proteome from differently acclimated Daphnia pulex. RESULTS: Specific sets of proteins were found to be differentially expressed in 10°C or 20°C acclimated D. pulex. Most cold-repressed proteins comprised secretory enzymes which are involved in protein digestion (trypsins, chymotrypsins, astacin, carboxypeptidases). The cold-induced sets of proteins included several vitellogenin and actin isoforms (cytoplasmic and muscle-specific), and an AAA+ ATPase. Carbohydrate-modifying enzymes were constitutively expressed or down-regulated in the cold. CONCLUSION: Specific sets of cold-repressed and cold-induced proteins in D. pulex can be related to changes in the cellular demand for amino acids or to the compensatory control of physiological processes. The increase of proteolytic enzyme concentration and the decrease of vitellogenin, actin and total protein concentration between 10°C and 20°C acclimated animals reflect the increased amino-acids demand and the reduced protein reserves in the animal's body. Conversely, the increase of actin concentration in cold-acclimated animals may contribute to a compensatory mechanism which ensures the relative constancy of muscular performance. The sheer number of peptidase genes (serine-peptidase-like: > 200, astacin-like: 36, carboxypeptidase-like: 30) in the D. pulex genome suggests large-scaled gene family expansions that might reflect specific adaptations to the lifestyle of a planktonic filter feeder in a highly variable aquatic environment.",2009 Apr 21,"['Schwerin, Susanne', 'Zeis, Bettina', 'Lamkemeyer, Tobias', 'Paul, Rüdiger J', 'Koch, Marita', 'Madlung, Johannes', 'Fladerer, Claudia', 'Pirow, Ralph']",BMC Physiol,,,False
13c8501740d1be695a284293351dd9181c0aba9a,PMC,Acclimatory responses of the Daphnia pulex proteome to environmental changes. II. Chronic exposure to different temperatures (10 and 20°C) mainly affects protein metabolism,http://dx.doi.org/10.1186/1472-6793-9-8,PMC2678069,19383147,CC BY,"BACKGROUND: Temperature affects essentially every aspect of the biology of poikilothermic animals including the energy and mass budgets, activity, growth, and reproduction. While thermal effects in ecologically important groups such as daphnids have been intensively studied at the ecosystem level and at least partly at the organismic level, much less is known about the molecular mechanisms underlying the acclimation to different temperatures. By using 2D gel electrophoresis and mass spectrometry, the present study identified the major elements of the temperature-induced subset of the proteome from differently acclimated Daphnia pulex. RESULTS: Specific sets of proteins were found to be differentially expressed in 10°C or 20°C acclimated D. pulex. Most cold-repressed proteins comprised secretory enzymes which are involved in protein digestion (trypsins, chymotrypsins, astacin, carboxypeptidases). The cold-induced sets of proteins included several vitellogenin and actin isoforms (cytoplasmic and muscle-specific), and an AAA+ ATPase. Carbohydrate-modifying enzymes were constitutively expressed or down-regulated in the cold. CONCLUSION: Specific sets of cold-repressed and cold-induced proteins in D. pulex can be related to changes in the cellular demand for amino acids or to the compensatory control of physiological processes. The increase of proteolytic enzyme concentration and the decrease of vitellogenin, actin and total protein concentration between 10°C and 20°C acclimated animals reflect the increased amino-acids demand and the reduced protein reserves in the animal's body. Conversely, the increase of actin concentration in cold-acclimated animals may contribute to a compensatory mechanism which ensures the relative constancy of muscular performance. The sheer number of peptidase genes (serine-peptidase-like: > 200, astacin-like: 36, carboxypeptidase-like: 30) in the D. pulex genome suggests large-scaled gene family expansions that might reflect specific adaptations to the lifestyle of a planktonic filter feeder in a highly variable aquatic environment.",2009 Apr 21,"['Schwerin, Susanne', 'Zeis, Bettina', 'Lamkemeyer, Tobias', 'Paul, Rüdiger J', 'Koch, Marita', 'Madlung, Johannes', 'Fladerer, Claudia', 'Pirow, Ralph']",BMC Physiol,,,False
1eb37c6ac1e51907a8a1d5f31c45fff08737cb36,PMC,Systems biology coupled with label-free high-throughput detection as a novel approach for diagnosis of chronic obstructive pulmonary disease,http://dx.doi.org/10.1186/1465-9921-10-29,PMC2678087,19386108,CC BY,"Chronic obstructive pulmonary disease (COPD) is a treatable and preventable disease state, characterised by progressive airflow limitation that is not fully reversible. Although COPD is primarily a disease of the lungs there is now an appreciation that many of the manifestations of disease are outside the lung, leading to the notion that COPD is a systemic disease. Currently, diagnosis of COPD relies on largely descriptive measures to enable classification, such as symptoms and lung function. Here the limitations of existing diagnostic strategies of COPD are discussed and systems biology approaches to diagnosis that build upon current molecular knowledge of the disease are described. These approaches rely on new 'label-free' sensing technologies, such as high-throughput surface plasmon resonance (SPR), that we also describe.",2009 Apr 22,"['Richens, Joanna L', 'Urbanowicz, Richard A', 'Lunt, Elizabeth AM', 'Metcalf, Rebecca', 'Corne, Jonathan', 'Fairclough, Lucy', ""O'Shea, Paul""]",Respir Res,,,True
aaaf05c5781726bd7c58cffa351a651580893257,PMC,Linkages between animal and human health sentinel data,http://dx.doi.org/10.1186/1746-6148-5-15,PMC2679002,19389228,CC BY,"INTRODUCTION: In order to identify priorities for building integrated surveillance systems that effectively model and predict human risk of zoonotic diseases, there is a need for improved understanding of the practical options for linking surveillance data of animals and humans. We conducted an analysis of the literature and characterized the linkage between animal and human health data. We discuss the findings in relation to zoonotic surveillance and the linkage of human and animal data. METHODS: The Canary Database, an online bibliographic database of animal-sentinel studies was searched and articles were classified according to four linkage categories. RESULTS: 465 studies were identified and assigned to linkage categories involving: descriptive, analytic, molecular, or no human outcomes of human and animal health. Descriptive linkage was the most common, whereby both animal and human health outcomes were presented, but without quantitative linkage between the two. Rarely, analytic linkage was utilized in which animal data was used to quantitatively predict human risk. The other two categories included molecular linkage, and no human outcomes, which present health outcomes in animals but not humans. DISCUSSION: We found limited use of animal data to quantitatively predict human risk and listed the methods from the literature that performed analytic linkage. The lack of analytic linkage in the literature might not be solely related to technological barriers including access to electronic database, statistical software packages, and Geographical Information System (GIS). Rather, the problem might be from a lack of understanding by researchers of the importance of animal data as a 'sentinel' for human health. Researchers performing zoonotic surveillance should be aware of the value of animal-sentinel approaches for predicting human risk and consider analytic methods for linking animal and human data. Qualitative work needs to be done in order to examine researchers' decisions in linkage strategies between animal and human data.",2009 Apr 23,"['Scotch, Matthew', 'Odofin, Lynda', 'Rabinowitz, Peter']",BMC Vet Res,,,True
3a693a23a7b7c13330611d995ea9d8861203c8b9,PMC,Wild canids as sentinels of ecological health: a conservation medicine perspective,http://dx.doi.org/10.1186/1756-3305-2-S1-S7,PMC2679399,19426446,CC BY,"The extinction of species across the globe is accelerating, directly or indirectly due to human activities. Biological impoverishment, habitat fragmentation, climate change, increasing toxification, and the rapid global movement of people and other living organisms have worked synergistically to diminish ecosystem function. This has resulted in unprecedented levels of disease emergence, driven by human-induced environmental degradation, which poses a threat to the survival and health of biodiversity. The emerging discipline of conservation medicine addresses these concerns through the following entities: humans; global climate; habitat destruction and alteration; biodiversity, including wildlife populations; domestic animals; and pathogens, parasites and pollutants. Furthermore, conservation medicine focuses on explicit linkages between these entities. As a crisis discipline, the usefulness of conservation medicine ultimately will depend on its applicability to solving problems. The perspectives and scientific findings of conservation medicine provide input into biomedical education; and policy and management of ecosystems, habitats and imperiled species. A sentinel species is one that has presented itself, or has been selected, to provide insight into the state (health) of an ecosystem, based on user-defined (e.g., researchers, conservationists or policymakers) objectives (e.g., disease, parasites, toxics, climate change, habitat destruction), coupled with the utility and vulnerability of this species to the perceived stress. The scientific information generated by the sentinel species should empower stakeholders and decision-makers to take mitigative action or support predictive capabilities; the ""utility"" of the species selected should consider its value and relevance to conservationists and to society at large (e.g., education and outreach; social sciences). Wild canids may serve as excellent sentinel species of emerging canine vector-borne diseases. Several canine vector-borne diseases or antibodies to these pathogens have been identified in wild canids including visceral leishmaniosis, Lyme disease, heartworm, hepatozoonosis and anaplasmosis to name a few. These reports are relatively recent as they relate to wildlife-domestic animal interactions, globalisation, translocations, habitat fragmentation and climate change. These pathogens and their relationship to wild canids are described herein. Further research needs to be performed to elucidate the role of the 36 extant species of wild canids in the epidemiology of canine vector-borne diseases.",2009 Mar 26,"Aguirre, A Alonso",Parasit Vectors,,,True
10fc3f71e291a910975b698e2158d15e96658bab,PMC,Autonomous Tetramerization Domains in the Glycan-binding Receptors DC-SIGN and DC-SIGNR,http://dx.doi.org/10.1016/j.jmb.2009.02.046,PMC2680971,19249311,CC BY,"Multivalent binding of glycans on pathogens and on mammalian cells by the receptors DC-SIGN (CD209) and DC-SIGNR (L-SIGN, CD299) is dependent on correct disposition of the C-type carbohydrate-recognition domains projected at the C-terminal ends of necks at the cell surface. In the work reported here, neck domains of DC-SIGN and DC-SIGNR expressed in isolation are shown to form tetramers in the absence of the CRDs. Stability analysis indicates that interactions between the neck domains account fully for the stability of the tetrameric extracellular portions of the receptors. The neck domains are approximately 40% α-helical based on circular dichroism analysis. However, in contrast to other glycan-binding receptors in which fully helical neck regions are intimately associated with C-terminal C-type CRDs, the neck domains in DC-SIGN and DC-SIGNR act as autonomous tetramerization domains and the neck domains and CRDs are organized independently. Neck domains from polymorphic forms of DC-SIGNR that lack some of the repeat sequences show modestly reduced stability, but differences near the C-terminal end of the neck domains lead to significantly enhanced stability of DC-SIGNR tetramers compared to DC-SIGN.",2009 Apr 17,"['Yu, Quan D.', 'Oldring, Asa P.', 'Powlesland, Alex S.', 'Tso, Cynthia K.W.', 'Yang, Chunxuan', 'Drickamer, Kurt', 'Taylor, Maureen E.']",J Mol Biol,,,False
920282c7a0656a43143be9b656b36367cf871c08,PMC,Combination Therapy Using Chimeric Monoclonal Antibodies Protects Mice from Lethal H5N1 Infection and Prevents Formation of Escape Mutants,http://dx.doi.org/10.1371/journal.pone.0005672,PMC2682562,19478856,CC BY,"BACKGROUND: Given that there is a possibility of a human H5N1 pandemic and the fact that the recent H5N1 viruses are resistant to the anti-viral drugs, newer strategies for effective therapy are warranted. Previous studies show that single mAbs in immune prophylaxis can be protective against H5N1 infection. But a single mAb may not be effective in neutralization of a broad range of different strains of H5N1 and control of potential neutralization escape mutants. METHODS/PRINCIPAL FINDINGS: We selected two mAbs which recognized different epitopes on the hemagglutinin molecule. These two mAbs could each neutralize in vitro escape mutants to the other and in combination could effectively neutralize viruses from clades 0, 1, 2.1, 2.2, 2.3, 4, 7 and 8 of influenza A H5N1 viruses. This combination of chimeric mAbs when administered passively, pre or post challenge with 10 MLD50 (50% mouse lethal dose) HPAI H5N1 influenza A viruses could protect 100% of the mice from two different clades of viruses (clades 1 and 2.1). We also tested the efficacy of a single dose of the combination of mAbs versus two doses. Two doses of the combination therapy not only affected early clearance of the virus from the lung but could completely prevent lung pathology of the H5N1 infected mice. No escape variants were detected after therapy. CONCLUSIONS/SIGNIFICANCE: Our studies provide proof of concept that the synergistic action of two or more mAbs in combination is required for preventing the generation of escape mutants and also to enhance the therapeutic efficacy of passive therapy against H5N1 infection. Combination therapy may allow for a lower dose of antibody to be administered for passive therapy of influenza infection and hence can be made available at reduced economic costs during an outbreak.",2009 May 22,"['Prabakaran, Mookkan', 'Prabhu, Nayana', 'He, Fang', 'Hongliang, Qian', 'Ho, Hui-Ting', 'Qiang, Jia', 'TaoMeng,', 'Goutama, Michael', 'Kwang, Jimmy']",PLoS One,,,True
404bf0836c388f561f796369c26d0bbf6f37b407,PMC,Small Interfering RNA Targeting M2 Gene Induces Effective and Long Term Inhibition of Influenza A Virus Replication,http://dx.doi.org/10.1371/journal.pone.0005671,PMC2682565,19479060,CC BY,"RNA interference (RNAi) provides a powerful new means to inhibit viral infection specifically. However, the selection of siRNA-resistant viruses is a major concern in the use of RNAi as antiviral therapeutics. In this study, we conducted a lentiviral vector with a H1-short hairpin RNA (shRNA) expression cassette to deliver small interfering RNAs (siRNAs) into mammalian cells. Using this vector that also expresses enhanced green fluorescence protein (EGFP) as surrogate marker, stable shRNA-expressing cell lines were successfully established and the inhibition efficiencies of rationally designed siRNAs targeting to conserved regions of influenza A virus genome were assessed. The results showed that a siRNA targeting influenza M2 gene (siM2) potently inhibited viral replication. The siM2 was not only effective for H1N1 virus but also for highly pathogenic avian influenza virus H5N1. In addition to its M2 inhibition, the siM2 also inhibited NP mRNA accumulation and protein expression. A long term inhibition effect of the siM2 was demonstrated and the emergence of siRNA-resistant mutants in influenza quasispecies was not observed. Taken together, our study suggested that M2 gene might be an optimal RNAi target for antiviral therapy. These findings provide useful information for the development of RNAi-based prophylaxis and therapy for human influenza virus infection.",2009 May 22,"['Sui, Hong-Yan', 'Zhao, Guang-Yu', 'Huang, Jian-Dong', 'Jin, Dong-Yan', 'Yuen, Kwok-Yung', 'Zheng, Bo-Jian']",PLoS One,,,True
20b02257b13e1631fe457bc81ed2b6033baee43e,PMC,Lack of association between polymorphisms of MASP2 and susceptibility to SARS coronavirus infection,http://dx.doi.org/10.1186/1471-2334-9-51,PMC2683852,19405982,CC BY,"BACKGROUND: The pathogenesis of severe acute respiratory disease syndrome (SARS) is not fully understood. One case-control study has reported an association between susceptibility to SARS and mannan-binding lectin (MBL) in China. As the downstream protein of MBL, variants of the MBL-associated serine protease-2 (MASP2) gene may be associated with SARS coronavirus (SARS-CoV) infection in the same population. METHODS: Thirty individuals with SARS were chosen for analysis of MASP2 polymorphisms by means of PCR direct sequencing. Tag single nucleotide polymorphisms (tagSNPs) were chosen using pairwise tagging algorithms. The frequencies of four tag SNPs (rs12711521, rs2261695, rs2273346 and rs7548659) were ascertained in 376 SARS patients and 523 control subjects, using the Beckman SNPstream Ultra High Throughput genotyping platform. RESULTS: There is no significant association between alleles or genotypes of the MASP2 tagSNP and susceptibility to SARS-CoV in both Beijing and Guangzhou populations. Diplotype (rs2273346 and rs12711521)were analyzed for association with susceptibility to SARS, no statistically significant evidence of association was observed. The Beijing and Guangzhou sample groups were homogeneous regarding demographic and genetic parameters, a joined analysis also showed no statistically significant evidence of association. CONCLUSION: Our data do not suggest a role for MASP2 polymorphisms in SARS susceptibility in northern and southern China.",2009 May 1,"['Wang, Yan', 'Yan, Jiangwei', 'Shi, Yuling', 'Li, Ping', 'Liu, Chuanxuan', 'Ma, Qingjun', 'Yang, Ruifu', 'Wang, Xiaoyi', 'zhu, Lina', 'Yang, Xiao', 'Cao, Cheng']",BMC Infect Dis,,,True
e30e44f2eb7f2effe677e665ad14ad511ac17c3f,PMC,Non-Molecular-Clock-Like Evolution following Viral Origins in Homo sapiens,,PMC2684125,19461973,CC BY,"Researchers routinely adopt molecular clock assumptions in conducting sequence analyses to estimate dates for viral origins in humans. We used computational methods to examine the extent to which this practice can result in inaccurate ‘retrodiction.’ Failing to account for dynamic molecular evolution can affect greatly estimating index case dates, resulting in an overestimated age for the SARS-CoV-human infection, for instance.",2007 Sep 26,"['Mok, Wendy', 'Seto, Kelly', 'Stone, Jon']",Evol Bioinform Online,,,True
d3b9423ca41bdd129766dce07506a87b9eec22a7,PMC,"Genome Signatures, Self-Organizing Maps and Higher Order Phylogenies: A Parametric Analysis",,PMC2684143,19468314,CC BY,"Genome signatures are data vectors derived from the compositional statistics of DNA. The self-organizing map (SOM) is a neural network method for the conceptualisation of relationships within complex data, such as genome signatures. The various parameters of the SOM training phase are investigated for their effect on the accuracy of the resulting output map. It is concluded that larger SOMs, as well as taking longer to train, are less sensitive in phylogenetic classification of unknown DNA sequences. However, where a classification can be made, a larger SOM is more accurate. Increasing the number of iterations in the training phase of the SOM only slightly increases accuracy, without improving sensitivity. The optimal length of the DNA sequence k-mer from which the genome signature should be derived is 4 or 5, but shorter values are almost as effective. In general, these results indicate that small, rapidly trained SOMs are generally as good as larger, longer trained ones for the analysis of genome signatures. These results may also be more generally applicable to the use of SOMs for other complex data sets, such as microarray data.",2007 Sep 17,"Gatherer, Derek",Evol Bioinform Online,,,True
8013bbf01944aa3f25d0faf16386ea51c7586066,PMC,Generation of Phaseolus vulgaris ESTs and investigation of their regulation upon Uromyces appendiculatus infection,http://dx.doi.org/10.1186/1471-2229-9-46,PMC2684537,19397807,CC BY,"BACKGROUND: Phaseolus vulgaris (common bean) is the second most important legume crop in the world after soybean. Consequently, yield losses due to fungal infection, like Uromyces appendiculatus (bean rust), have strong consequences. Several resistant genes were identified that confer resistance to bean rust infection. However, the downstream genes and mechanisms involved in bean resistance to infection are poorly characterized. RESULTS: A subtractive bean cDNA library composed of 10,581 unisequences was constructed and enriched in sequences regulated by either bean rust race 41, a virulent strain, or race 49, an avirulent strain on cultivar Early Gallatin carrying the resistance gene Ur-4. The construction of this library allowed the identification of 6,202 new bean ESTs, significantly adding to the available sequences for this plant. Regulation of selected bean genes in response to bean rust infection was confirmed by qRT-PCR. Plant gene expression was similar for both race 41 and 49 during the first 48 hours of the infection process but varied significantly at the later time points (72–96 hours after inoculation) mainly due to the presence of the Avr4 gene in the race 49 leading to a hypersensitive response in the bean plants. A biphasic pattern of gene expression was observed for several genes regulated in response to fungal infection. CONCLUSION: The enrichment of the public database with over 6,000 bean ESTs significantly adds to the genomic resources available for this important crop plant. The analysis of these genes in response to bean rust infection provides a foundation for further studies of the mechanism of fungal disease resistance. The expression pattern of 90 bean genes upon rust infection shares several features with other legumes infected by biotrophic fungi. This finding suggests that the P. vulgaris-U. appendiculatus pathosystem could serve as a model to explore legume-rust interaction.",2009 Apr 27,"['Thibivilliers, Sandra', 'Joshi, Trupti', 'Campbell, Kimberly B', 'Scheffler, Brian', 'Xu, Dong', 'Cooper, Bret', 'Nguyen, Henry T', 'Stacey, Gary']",BMC Plant Biol,,,True
75435342678d143b3fea48a288d1baa113d28a42,PMC,Applying the balanced scorecard to local public health performance measurement: deliberations and decisions,http://dx.doi.org/10.1186/1471-2458-9-127,PMC2684743,19426508,CC BY,"BACKGROUND: All aspects of the heath care sector are being asked to account for their performance. This poses unique challenges for local public health units with their traditional focus on population health and their emphasis on disease prevention, health promotion and protection. Reliance on measures of health status provides an imprecise and partial picture of the performance of a health unit. In 2004 the provincial Institute for Clinical Evaluative Sciences based in Ontario, Canada introduced a public-health specific balanced scorecard framework. We present the conceptual deliberations and decisions undertaken by a health unit while adopting the framework. DISCUSSION: Posing, pondering and answering key questions assisted in applying the framework and developing indicators. Questions such as: Who should be involved in developing performance indicators? What level of performance should be measured? Who is the primary intended audience? Where and how do we begin? What types of indicators should populate the health status and determinants quadrant? What types of indicators should populate the resources and services quadrant? What type of indicators should populate the community engagement quadrant? What types of indicators should populate the integration and responsiveness quadrants? Should we try to link the quadrants? What comparators do we use? How do we move from a baseline report card to a continuous quality improvement management tool? SUMMARY: An inclusive, participatory process was chosen for defining and creating indicators to populate the four quadrants. Examples of indicators that populate the four quadrants of the scorecard are presented and key decisions are highlighted that facilitated the process.",2009 May 8,"['Weir, Erica', ""d'Entremont, Nadine"", 'Stalker, Shelley', 'Kurji, Karim', 'Robinson, Victoria']",BMC Public Health,,,True
7433a628e7fe85066cddc5c25a416fea3ffa87e5,PMC,Inhibition of Lassa Virus Glycoprotein Cleavage and Multicycle Replication by Site 1 Protease-Adapted α(1)-Antitrypsin Variants,http://dx.doi.org/10.1371/journal.pntd.0000446,PMC2685025,19488405,CC BY,"BACKGROUND: Proteolytic processing of the Lassa virus envelope glycoprotein precursor GP-C by the host proprotein convertase site 1 protease (S1P) is a prerequisite for the incorporation of the subunits GP-1 and GP-2 into viral particles and, hence, essential for infectivity and virus spread. Therefore, we tested in this study the concept of using S1P as a target to block efficient virus replication. METHODOLOGY/PRINCIPAL FINDING: We demonstrate that stable cell lines inducibly expressing S1P-adapted α(1)-antitrypsin variants inhibit the proteolytic maturation of GP-C. Introduction of the S1P recognition motifs RRIL and RRLL into the reactive center loop of α(1)-antitrypsin resulted in abrogation of GP-C processing by endogenous S1P to a similar level observed in S1P-deficient cells. Moreover, S1P-specific α(1)-antitrypsins significantly inhibited replication and spread of a replication-competent recombinant vesicular stomatitis virus expressing the Lassa virus glycoprotein GP as well as authentic Lassa virus. Inhibition of viral replication correlated with the ability of the different α(1)-antitrypsin variants to inhibit the processing of the Lassa virus glycoprotein precursor. CONCLUSIONS/SIGNIFICANCE: Our data suggest that glycoprotein cleavage by S1P is a promising target for the development of novel anti-arenaviral strategies.",2009 Jun 2,"['Maisa, Anna', 'Ströher, Ute', 'Klenk, Hans-Dieter', 'Garten, Wolfgang', 'Strecker, Thomas']",PLoS Negl Trop Dis,,,True
8f974201b04925c9627c032739f86f06cf5fdcf5,PMC,Inhibition of Lassa Virus Glycoprotein Cleavage and Multicycle Replication by Site 1 Protease-Adapted α(1)-Antitrypsin Variants,http://dx.doi.org/10.1371/journal.pntd.0000446,PMC2685025,19488405,CC BY,"BACKGROUND: Proteolytic processing of the Lassa virus envelope glycoprotein precursor GP-C by the host proprotein convertase site 1 protease (S1P) is a prerequisite for the incorporation of the subunits GP-1 and GP-2 into viral particles and, hence, essential for infectivity and virus spread. Therefore, we tested in this study the concept of using S1P as a target to block efficient virus replication. METHODOLOGY/PRINCIPAL FINDING: We demonstrate that stable cell lines inducibly expressing S1P-adapted α(1)-antitrypsin variants inhibit the proteolytic maturation of GP-C. Introduction of the S1P recognition motifs RRIL and RRLL into the reactive center loop of α(1)-antitrypsin resulted in abrogation of GP-C processing by endogenous S1P to a similar level observed in S1P-deficient cells. Moreover, S1P-specific α(1)-antitrypsins significantly inhibited replication and spread of a replication-competent recombinant vesicular stomatitis virus expressing the Lassa virus glycoprotein GP as well as authentic Lassa virus. Inhibition of viral replication correlated with the ability of the different α(1)-antitrypsin variants to inhibit the processing of the Lassa virus glycoprotein precursor. CONCLUSIONS/SIGNIFICANCE: Our data suggest that glycoprotein cleavage by S1P is a promising target for the development of novel anti-arenaviral strategies.",2009 Jun 2,"['Maisa, Anna', 'Ströher, Ute', 'Klenk, Hans-Dieter', 'Garten, Wolfgang', 'Strecker, Thomas']",PLoS Negl Trop Dis,,,False
061f81e4132c9d443b9afa644a32fb23d75db2f7,PMC,Inhibition of Lassa Virus Glycoprotein Cleavage and Multicycle Replication by Site 1 Protease-Adapted α(1)-Antitrypsin Variants,http://dx.doi.org/10.1371/journal.pntd.0000446,PMC2685025,19488405,CC BY,"BACKGROUND: Proteolytic processing of the Lassa virus envelope glycoprotein precursor GP-C by the host proprotein convertase site 1 protease (S1P) is a prerequisite for the incorporation of the subunits GP-1 and GP-2 into viral particles and, hence, essential for infectivity and virus spread. Therefore, we tested in this study the concept of using S1P as a target to block efficient virus replication. METHODOLOGY/PRINCIPAL FINDING: We demonstrate that stable cell lines inducibly expressing S1P-adapted α(1)-antitrypsin variants inhibit the proteolytic maturation of GP-C. Introduction of the S1P recognition motifs RRIL and RRLL into the reactive center loop of α(1)-antitrypsin resulted in abrogation of GP-C processing by endogenous S1P to a similar level observed in S1P-deficient cells. Moreover, S1P-specific α(1)-antitrypsins significantly inhibited replication and spread of a replication-competent recombinant vesicular stomatitis virus expressing the Lassa virus glycoprotein GP as well as authentic Lassa virus. Inhibition of viral replication correlated with the ability of the different α(1)-antitrypsin variants to inhibit the processing of the Lassa virus glycoprotein precursor. CONCLUSIONS/SIGNIFICANCE: Our data suggest that glycoprotein cleavage by S1P is a promising target for the development of novel anti-arenaviral strategies.",2009 Jun 2,"['Maisa, Anna', 'Ströher, Ute', 'Klenk, Hans-Dieter', 'Garten, Wolfgang', 'Strecker, Thomas']",PLoS Negl Trop Dis,,,False
a0c2551d031c6dd3f59392c3f75dffc7b694a186,PMC,T. cruzi OligoC-TesT: A Simplified and Standardized Polymerase Chain Reaction Format for Diagnosis of Chagas Disease,http://dx.doi.org/10.1371/journal.pntd.0000450,PMC2685481,19503815,CC BY,"BACKGROUND: PCR has evolved into one of the most promising tools for T. cruzi detection in the diagnosis and control of Chagas disease. However, general use of the technique is hampered by its complexity and the lack of standardization. METHODOLOGY: We here present the development and phase I evaluation of the T. cruzi OligoC-TesT, a simple and standardized dipstick format for detection of PCR amplified T. cruzi DNA. The specificity and sensitivity of the assay were evaluated on blood samples from 60 Chagas non-endemic and 48 endemic control persons and on biological samples from 33 patients, 7 reservoir animals, and 14 vectors collected in Chile. PRINCIPAL FINDINGS: The lower detection limits of the T. cruzi OligoC-TesT were 1 pg and 1 to 10 fg of DNA from T. cruzi lineage I and II, respectively. The test showed a specificity of 100% (95% confidence interval [CI]: 96.6%–100%) on the control samples and a sensitivity of 93.9% (95% CI: 80.4%–98.3%), 100% (95% CI: 64.6%–100%), and 100% (95% CI: 78.5%–100%) on the human, rodent, and vector samples, respectively. CONCLUSIONS: The T. cruzi OligoC-TesT showed high sensitivity and specificity on a diverse panel of biological samples. The new tool is an important step towards simplified and standardized molecular diagnosis of Chagas disease.",2009 Jun 2,"['Deborggraeve, Stijn', 'Coronado, Ximena', 'Solari, Aldo', 'Zulantay, Ines', 'Apt, Werner', 'Mertens, Pascal', 'Laurent, Thierry', 'Leclipteux, Thierry', 'Stessens, Tim', 'Dujardin, Jean-Claude', 'Herdewijn, Piet', 'Büscher, Philippe']",PLoS Negl Trop Dis,,,True
46ee8e5fc43eba4d4efe8979ba75a36991d9e283,PMC,The study on the outsourcing of Taiwan's hospitals: a questionnaire survey research,http://dx.doi.org/10.1186/1472-6963-9-78,PMC2685796,19435526,CC BY,"BACKGROUND: The aim of this study was to assess the outsourcing situation in Taiwanese hospitals and compares the differences in hospital ownership and in accreditation levels. METHODS: This research combined two kinds of methods: a questionnaire survey and the in-depth interview to two CEOs of the sample hospitals. One hospital is not-for-profit, while the other is a public hospital and the research samples are from the hospital data from Taiwan's 2005 to 2007 Department of Health qualifying lists of hospital accreditation. The returned questionnaires were analyzed with STATISTICA(® )7.1 version software. RESULTS: The results for non-medical items showed medical waste and common trash both have the highest rate (94.6 percent) of being outsourced. The gift store (75 percent) and linen (73 percent) follow close behind, while the lowest rate of outsourcing is in utility maintenance (13.5 percent). For medical items, the highest rate of outsourcing is in the ambulance units (51.4 percent), while the hemodialysis center follows close behind with a rate of 50 percent. For departments of nutrition, pharmacy, and nursing however, the outsourcing rate is lower than 3 percent. This shows that Taiwan's hospitals are still conservative in their willingness to outsource for medical items. The results of the satisfaction paired t-test show that the non-medical items have a higher score than the medical items. The factor analysis showed the three significant factors in of non medical items' outsourcing are ""performance"", ""finance"", and ""human resource"". For medical items, the two factors are ""operation"" and satisfaction"". To further exam the factor validity and reliability of the satisfaction model, a confirmative factor analysis (CFA) was conducted using structure equation modeling (SEM) method and found the model fitting well. CONCLUSION: Hospitals, especially for public hospitals, can get benefits from outsourcing to revive the full-time-equivalent and human resource limitation.",2009 May 13,"['Hsiao, Chih-Tung', 'Pai, Jar-Yuan', 'Chiu, Hero']",BMC Health Serv Res,,,True
5f14950df2d6d428b1dff4d58e7775f92da020d7,PMC,Detection of Colorectal Cancer by Serum and Tissue Protein Profiling: A Prospective Study in a Population at Risk,,PMC2688344,19578519,CC BY,"Colorectal cancer (CRC) is the second most common cause of cancer-related death in Europe and its prognosis is largely dependent on stage at diagnosis. Currently, there are no suitable tumour markers for early detection of CRC. In a retrospective study we previously found discriminative CRC serum protein profiles with surface enhanced laser desorption ionisation—time of flight mass spectrometry (SELDI-TOF MS). We now aimed at prospective validation of these profiles. Additionally, we assessed their applicability for follow-up after surgery and investigated tissue protein profiles of patients with CRC and adenomatous polyps (AP). Serum and tissue samples were collected from patients without known malignancy with an indication for colonoscopy and patients with AP and CRC during colonoscopy. Serum samples of controls (CON; n = 359), patients with AP (n = 177) and CRC (n = 73), as well as tissue samples from AP (n = 52) and CRC (n = 47) were analysed as described previously. Peak intensities were compared by non-parametric testing. Discriminative power of differentially expressed proteins was assessed with support vector machines (SVM). We confirmed the decreased serum levels of apolipoprotein C-1 in CRC in the current population. No differences were observed between CON and AP. Apolipoprotein C-I levels did not change significantly within 1 month post-surgery, although a gradual return to normal levels was observed. Several proteins differed between AP and CRC tissue, among which a peak with similar mass as apolipoprotein C-1. This peak was increased in CRC compared to AP. Although we prospectively validated the serum decrease of apolipoprotein C-1 in CRC, serum protein profiles did not yield SVM classifiers with suitable sensitivity and specificity for classification of our patient groups.",2008 Jul 2,"['Engwegen, Judith Y.M.N.', 'Depla, Annekatrien C.T.M.', 'Smits, Marianne E.', 'Cats, Annemieke', 'Tuynman, Henriëtte', 'van Heukelem, Henk A.', 'Snel, Pleun', 'Meuleman, Wouter', 'Wessels, Lodewyk F.', 'Schellens, Jan H.M.', 'Beijnen, Jos H.']",Biomark Insights,,,True
d5794d9e687b1087383f2bca0c5beaf31ebc2955,PMC,A Statistical Framework for the Adaptive Management of Epidemiological Interventions,http://dx.doi.org/10.1371/journal.pone.0005807,PMC2688756,19503812,CC BY,"BACKGROUND: Epidemiological interventions aim to control the spread of infectious disease through various mechanisms, each carrying a different associated cost. METHODOLOGY: We describe a flexible statistical framework for generating optimal epidemiological interventions that are designed to minimize the total expected cost of an emerging epidemic while simultaneously propagating uncertainty regarding the underlying disease model parameters through to the decision process. The strategies produced through this framework are adaptive: vaccination schedules are iteratively adjusted to reflect the anticipated trajectory of the epidemic given the current population state and updated parameter estimates. CONCLUSIONS: Using simulation studies based on a classic influenza outbreak, we demonstrate the advantages of adaptive interventions over non-adaptive ones, in terms of cost and resource efficiency, and robustness to model misspecification.",2009 Jun 5,"['Merl, Daniel', 'Johnson, Leah R.', 'Gramacy, Robert B.', 'Mangel, Marc']",PLoS One,,,True
7c0a15a70be63f9707358fb640e01b464e54dfd0,PMC,Strategies for successful recombinant expression of disulfide bond-dependent proteins in Escherichia coli,http://dx.doi.org/10.1186/1475-2859-8-26,PMC2689190,19442264,CC BY,"Bacteria are simple and cost effective hosts for producing recombinant proteins. However, their physiological features may limit their use for obtaining in native form proteins of some specific structural classes, such as for instance polypeptides that undergo extensive post-translational modifications. To some extent, also the production of proteins that depending on disulfide bridges for their stability has been considered difficult in E. coli. Both eukaryotic and prokaryotic organisms keep their cytoplasm reduced and, consequently, disulfide bond formation is impaired in this subcellular compartment. Disulfide bridges can stabilize protein structure and are often present in high abundance in secreted proteins. In eukaryotic cells such bonds are formed in the oxidizing environment of endoplasmic reticulum during the export process. Bacteria do not possess a similar specialized subcellular compartment, but they have both export systems and enzymatic activities aimed at the formation and at the quality control of disulfide bonds in the oxidizing periplasm. This article reviews the available strategies for exploiting the physiological mechanisms of bactera to produce properly folded disulfide-bonded proteins.",2009 May 14,"de Marco, Ario",Microb Cell Fact,,,True
3bd416cb6ace33b8879fa9e93778de31ae256773,PMC,What Is the Optimal Therapy for Patients with H5N1 Influenza?,http://dx.doi.org/10.1371/journal.pmed.1000091,PMC2694988,19554084,CC BY,"In a 2007 article in PLoS Medicine [10], Holger J. Schünemann and colleagues described a new process used by the World Health Organization for rapidly developing clinical management guidelines in emergency situations. These situations include outbreaks of emerging infectious diseases. The authors discussed how they developed such a “rapid advice” guideline for the pharmacological management of avian influenza A (H5N1) virus infection. The guideline recommends giving the antiviral drug oseltamivir at a dose of 75 mg twice daily for five days. In this Debate, Nicholas White argues that such dosing is inadequate, Robert Webster and Elena Govorkova say that combination antiviral therapy should be used, and Tim Uyeki reminds us that clinical care of patients with H5N1 entails much more than antiviral treatment. These issues may also apply to therapy of patients hospitalized with severe disease due to novel swine-origin influenza A (H1N1) virus infection.",2009 Jun 23,"['White, Nicholas J.', 'Webster, Robert G.', 'Govorkova, Elena A.', 'Uyeki, Timothy M.']",PLoS Med,,,True
5813a786b66940f45bd1083081448cc53edcadd4,PMC,Development of TaqMan(® )MGB fluorescent real-time PCR assay for the detection of anatid herpesvirus 1,http://dx.doi.org/10.1186/1743-422X-6-71,PMC2696427,19497115,CC BY,"BACKGROUND: Anatid herpesvirus 1 (AHV-1) is an alphaherpesvirus associated with latent infection and mortality in ducks and geese and is currently affecting the world-wide waterfowl production severely. Here we describe a fluorescent quantitative real-time PCR (FQ-PCR) method developed for fast measurement of AHV-1 DNA based on TaqMan MGB technology. RESULTS: The detection limit of the assay was 1 × 10(1 )standard DNA copies, with a sensitivity of 2 logs higher than that of the conventional gel-based PCR assay targeting the same gene. The real-time PCR was reproducible, as shown by satisfactory low intra-assay and inter-assay coefficients of variation. CONCLUSION: The high sensitivity, specificity, simplicity and reproducibility of the AHV-1 fluorogenic PCR assay, combined with its wide dynamic range and high throughput, make this method suitable for a broad spectrum of AHV-1 etiologically related application.",2009 Jun 4,"['Guo, Yufei', 'Cheng, Anchun', 'Wang, Mingshu', 'Shen, Chanjuan', 'Jia, Renyong', 'Chen, Shun', 'Zhang, Na']",Virol J,,,True
e3785336f334b853b3d269a8301dfc564f5fae74,PMC,Association of the shuffling of Streptococcus pyogenes clones and the fluctuation of scarlet fever cases between 2000 and 2006 in central Taiwan,http://dx.doi.org/10.1186/1471-2180-9-115,PMC2697166,19486515,CC BY,"BACKGROUND: The number of scarlet fever occurrences reported between 2000 and 2006 fluctuated considerably in central Taiwan and throughout the nation. Isolates of Streptococcus pyogenes were collected from scarlet fever patients in central Taiwan and were characterized by emm sequencing and a standardized pulsed-field gel electrophoresis (PFGE) method. National weekly report data were collected for investigating epidemiological trends. RESULTS: A total of 23 emm types were identified in 1,218 S. pyogenes isolates. The five most prevalent emm types were emm12 (50.4%), emm4 (23.2%), emm1 (16.4%), emm6 (3.8%) and emm22 (3.0%). PFGE analysis with SmaI suggested that, with a few exceptions, strains with a common emm type belonged to the same clone. There were two large emm12 clones, one with DNA resistant to cleavage by SmaI. Each prevalent emm clone had major PFGE strain(s) and many minor strains. Most of the minor strains emerged in the population and disappeared soon after. Even some major strains remained prevalent for only 2–3 years before declining. The large fluctuation of scarlet fever cases between 2000 and 2006 was associated with the shuffling of six prevalent emm clones. In 2003, the dramatic drop in scarlet fever cases in central Taiwan and throughout the whole country was associated with the occurrence of a severe acute respiratory syndrome (SARS) outbreak that occurred between late-February and mid-June in Taiwan. CONCLUSION: The occurrences of scarlet fever in central Taiwan in 2000–2006 were primarily caused by five emm types, which accounted for 96.8% of the isolates collected. Most of the S. pyogenes strains (as defined by PFGE genotypes) emerged and lasted for only a few years. The fluctuation in the number of scarlet fever cases during the seven years can be primarily attributed to the shuffling of six prevalent emm clones and to the SARS outbreak in 2003.",2009 Jun 1,"['Chiou, Chien-Shun', 'Wang, You-Wun', 'Chen, Pei-Ling', 'Wang, Wan-Ling', 'Wu, Ping-Fuai', 'Wei, Hsiao-Lun']",BMC Microbiol,,,True
17d6161faae981aa6c56ac58d9c1d30ed581b05f,PMC,IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,http://dx.doi.org/10.1186/1471-2105-10-160,PMC2698906,19473520,CC BY,"BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.",2009 May 27,"['Wu, Tzong-Yuan', 'Hsieh, Chi-Chun', 'Hong, Jun-Jie', 'Chen, Chung-Yung', 'Tsai, Yuh-Show']",BMC Bioinformatics,,,True
f1b4911a5d641bccc19aec9b8b2cd02e1f0e11dd,PMC,IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,http://dx.doi.org/10.1186/1471-2105-10-160,PMC2698906,19473520,CC BY,"BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.",2009 May 27,"['Wu, Tzong-Yuan', 'Hsieh, Chi-Chun', 'Hong, Jun-Jie', 'Chen, Chung-Yung', 'Tsai, Yuh-Show']",BMC Bioinformatics,,,False
5e85e7bcf8d9f02e744c9fba06e78a2653a0e238,PMC,IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,http://dx.doi.org/10.1186/1471-2105-10-160,PMC2698906,19473520,CC BY,"BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.",2009 May 27,"['Wu, Tzong-Yuan', 'Hsieh, Chi-Chun', 'Hong, Jun-Jie', 'Chen, Chung-Yung', 'Tsai, Yuh-Show']",BMC Bioinformatics,,,False
9861f6865482d2353d77c8695eef0079539feeb0,PMC,IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,http://dx.doi.org/10.1186/1471-2105-10-160,PMC2698906,19473520,CC BY,"BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.",2009 May 27,"['Wu, Tzong-Yuan', 'Hsieh, Chi-Chun', 'Hong, Jun-Jie', 'Chen, Chung-Yung', 'Tsai, Yuh-Show']",BMC Bioinformatics,,,False
b79bd179bc542b31f7c76f7115c5a338dfa3c614,PMC,IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,http://dx.doi.org/10.1186/1471-2105-10-160,PMC2698906,19473520,CC BY,"BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.",2009 May 27,"['Wu, Tzong-Yuan', 'Hsieh, Chi-Chun', 'Hong, Jun-Jie', 'Chen, Chung-Yung', 'Tsai, Yuh-Show']",BMC Bioinformatics,,,False
97fa68ad1301de1773b18140530ef974ba6262a2,PMC,IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,http://dx.doi.org/10.1186/1471-2105-10-160,PMC2698906,19473520,CC BY,"BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.",2009 May 27,"['Wu, Tzong-Yuan', 'Hsieh, Chi-Chun', 'Hong, Jun-Jie', 'Chen, Chung-Yung', 'Tsai, Yuh-Show']",BMC Bioinformatics,,,False
ab5841bc722a51ed45cff24f1d419916b3a83427,PMC,IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,http://dx.doi.org/10.1186/1471-2105-10-160,PMC2698906,19473520,CC BY,"BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.",2009 May 27,"['Wu, Tzong-Yuan', 'Hsieh, Chi-Chun', 'Hong, Jun-Jie', 'Chen, Chung-Yung', 'Tsai, Yuh-Show']",BMC Bioinformatics,,,False
251158df2bf3b5bb57e84ff466737b9917df0fd1,PMC,IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,http://dx.doi.org/10.1186/1471-2105-10-160,PMC2698906,19473520,CC BY,"BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.",2009 May 27,"['Wu, Tzong-Yuan', 'Hsieh, Chi-Chun', 'Hong, Jun-Jie', 'Chen, Chung-Yung', 'Tsai, Yuh-Show']",BMC Bioinformatics,,,False
bad87b7effc9c6f6a9ef4ca024f7fe86daff4f45,PMC,Emerging trends in plasma-free manufacturing of recombinant protein therapeutics expressed in mammalian cells,http://dx.doi.org/10.1002/biot.200800241,PMC2699044,19226552,CC BY,"Mammalian cells are the expression system of choice for therapeutic proteins, especially those requiring complex post-translational modifications. Traditionally, these cells are grown in medium supplemented with serum and other animal-or human-derived components to support viability and productivity. Such proteins are also typically added as excipients and stabilizers in the final drug formulation. However, the transmission of hepatitis B in the 1970s and of hepatitis C and HIV in the 1980s through plasma-derived factor VIII concentrates had catastrophic consequences for hemophilia patients. Thus, due to regulatory concerns about the inherent potential for transmission of infectious agents as well as the heterogeneity and lack of reliability of the serum supply, a trend has emerged to eliminate the use of plasma-derived additives in the production and formulation of recombinant protein therapeutics. This practice began with products used in the treatment of hemophilia and is progressively expanding throughout the entire industry. The plasma-free method of producing recombinant therapeutics is accomplished by the use of both cell culture media and final product formulations that do not contain animal-or human-derived additives. A number of recombinant therapeutic proteins for the treatment of several different diseases have been produced by plasma-free processes, with the objective of improving safety by eliminating blood-borne pathogens or by reducing immunogenicity. This review describes the factors that drove the development of plasma-free protein therapeutics and provides examples of advances in manufacturing that have made possible the removal of human and animal-derived products from all steps of recombinant protein production.",2009 Feb,"['Grillberger, Leopold', 'Kreil, Thomas R', 'Nasr, Sonia', 'Reiter, Manfred']",Biotechnol J,,,True
c7b16abf574515b631f758dc51170ef757fd58b4,PMC,Lactate Dehydrogenase-Elevating Virus Induces Systemic Lymphocyte Activation via TLR7-Dependent IFNα Responses by Plasmacytoid Dendritic Cells,http://dx.doi.org/10.1371/journal.pone.0006105,PMC2699471,19568424,CC0,"BACKGROUND: Lactate dehydrogenase-elevating virus (LDV) is a natural infectious agent of mice. Like several other viruses, LDV causes widespread and very rapid but transient activation of both B cells and T cells in lymphoid tissues and the blood. The mechanism of this activation has not been fully described and is the focus of the current studies. PRINCIPAL FINDINGS: A known inducer of early lymphocyte activation is IFNα, a cytokine strongly induced by LDV infection. Neutralization of IFNα in the plasma from infected mice ablated its ability to activate lymphocytes in vitro. Since the primary source of virus-induced IFNα in vivo is often plasmacytoid dendritic cells (pDC's), we depleted these cells prior to LDV infection and tested for lymphocyte activation. Depletion of pDC's in vivo eradicated both the LDV-induced IFNα response and lymphocyte activation. A primary receptor in pDC's for single stranded RNA viruses such as LDV is the toll-like receptor 7 (TLR7) pattern recognition receptor. Infection of TLR7-knockout mice revealed that both the IFNα response and lymphocyte activation were dependent on TLR7 signaling in vivo. Interestingly, virus levels in both TLR7 knockout mice and pDC-depleted mice were indistinguishable from controls indicating that LDV is largely resistant to the systemic IFNα response. CONCLUSION: Results indicate that LDV-induced activation of lymphocytes is due to recognition of LDV nucleic acid by TLR7 pattern recognition receptors in pDC's that respond with a lymphocyte-inducing IFNα response.",2009 Jul 1,"['Ammann, Christoph G.', 'Messer, Ronald J.', 'Peterson, Karin E.', 'Hasenkrug, Kim J.']",PLoS One,,,True
6f048749badc8f1c756857ceb24421f5e6c05e62,PMC,Patterns of perception toward influenza pandemic among the front-line responsible health personnel in southern Thailand: a Q methodology approach,http://dx.doi.org/10.1186/1471-2458-9-161,PMC2700101,19473550,CC BY,"BACKGROUND: Thailand has joined the World Health Organization effort to prepare against a threat of an influenza pandemic. Regular monitoring on preparedness of health facilities and assessment on perception of the front-line responsible health personnel has never been done. This study aimed to document the patterns of perception of health personnel toward the threat of an influenza pandemic. METHODS: Q methodology was applied to a set of 385 health personnel in charge of influenza pandemic preparedness in the three southernmost provinces of Thailand. Subjects were asked to rank 33 statements about various issues of influenza pandemic according to a pre-designed score sheet having a quasi-normal distribution on a continuous 9-point bipolar scale ranging from -4 for strongly disagree to +4 for strongly agree. The Q factor analysis method was employed to identify patterns based on the similarity and dissimilarity among health personnel. RESULTS: There were three main patterns of perception toward influenza pandemic with moderate correlation coefficients between patterns ranging from 0.37 to 0.55. Pattern I, health personnel, which we labeled pessimistic, perceived themselves as having a low self-efficacy. Pattern II, which we labeled optimistic, perceived the threat to be low severity and low vulnerability. Pattern III, which we labeled mixed, perceived low self-efficacy but low vulnerability. Across the three patterns, almost all the subjects had a high expectancy that execution of recommended measures can mitigate impacts of the threat of an influenza pandemic, particularly on multi-measures with high factor scores of 4 in all patterns. The most conflicting area was vulnerability on the possible impacts of an influenza pandemic, having factor scores of high (3), low (-4), and neutral (0) for patterns I, II, and III, respectively. CONCLUSION: Strong consistent perceptions of response efficacy against an influenza pandemic may suggest a low priority to convince health personnel on the efficacy of the recommended measures. Lack of self-efficacy in certain sub-groups indicates the need for program managers to improve self-confidence of health personnel to participate in an emergency response.",2009 May 28,"['Prateepko, Tapanan', 'Chongsuvivatwong, Virasakdi']",BMC Public Health,,,True
b7bd823d7175ee551d3ba8508e5457d650056fd6,PMC,Acquisition of Cell–Cell Fusion Activity by Amino Acid Substitutions in Spike Protein Determines the Infectivity of a Coronavirus in Cultured Cells,http://dx.doi.org/10.1371/journal.pone.0006130,PMC2700284,19572016,CC BY,"Coronavirus host and cell specificities are determined by specific interactions between the viral spike (S) protein and host cell receptor(s). Avian coronavirus infectious bronchitis (IBV) has been adapted to embryonated chicken eggs, primary chicken kidney (CK) cells, monkey kidney cell line Vero, and other human and animal cells. Here we report that acquisition of the cell–cell fusion activity by amino acid mutations in the S protein determines the infectivity of IBV in cultured cells. Expression of S protein derived from Vero- and CK-adapted strains showed efficient induction of membrane fusion. However, expression of S protein cloned from the third passage of IBV in chicken embryo (EP3) did not show apparent syncytia formation. By construction of chimeric S constructs and site-directed mutagenesis, a point mutation (L857-F) at amino acid position 857 in the heptad repeat 1 region of S protein was shown to be responsible for its acquisition of the cell–cell fusion activity. Furthermore, a G405-D point mutation in the S1 domain, which was acquired during further propagation of Vero-adapted IBV in Vero cells, could enhance the cell–cell fusion activity of the protein. Re-introduction of L857 back to the S gene of Vero-adapted IBV allowed recovery of variants that contain the introduced L857. However, compensatory mutations in S1 and some distant regions of S2 were required for restoration of the cell–cell fusion activity of S protein carrying L857 and for the infectivity of the recovered variants in cultured cells. This study demonstrates that acquisition of the cell–cell fusion activity in S protein determines the selection and/or adaptation of a coronavirus from chicken embryo to cultured cells of human and animal origins.",2009 Jul 2,"['Yamada, Yoshiyuki', 'Liu, Xiao Bo', 'Fang, Shou Guo', 'Tay, Felicia P. L.', 'Liu, Ding Xiang']",PLoS One,,,True
a600310d78ebe675d0d7bc5d9188a77d73e0e79a,PMC,"Toll-like receptors, chemokine receptors and death receptor ligands responses in SARS coronavirus infected human monocyte derived dendritic cells",http://dx.doi.org/10.1186/1471-2172-10-35,PMC2700820,19505311,CC BY,"BACKGROUND: The SARS outbreak in 2003 provides a unique opportunity for the study of human responses to a novel virus. We have previously reported that dendritic cells (DCs) might be involved in the immune escape mechanisms for SARS-CoV. In this study, we focussed on the gene expression of toll-like receptors (TLRs), chemokine receptors (CCRs) and death receptor ligands in SARS-CoV infected DCs. We also compared adult and cord blood (CB) DCs to find a possible explanation for the age-dependent severity of SARS. RESULTS: Our results demonstrates that SARS-CoV did not modulate TLR-1 to TLR-10 gene expression but significantly induced the expression of CCR-1, CCR-3, and CCR-5. There was also strong induction of TNF-related apoptosis-inducing ligand (TRAIL), but not Fas ligand gene expression in SARS-CoV infected DCs. Interestingly, the expressions of most genes studied were higher in CB DCs than adult DCs. CONCLUSION: The upregulation of chemokines and CCRs may facilitate DC migration from the infection site to the lymph nodes, whereas the increase of TRAIL may induce lymphocyte apoptosis. These findings may explain the increased lung infiltrations and lymphoid depletion in SARS patients. Further explorations of the biological significance of these findings are warranted.",2009 Jun 8,"['Law, Helen KW', 'Cheung, Chung Yan', 'Sia, Sin Fun', 'Chan, Yuk On', 'Peiris, JS Malik', 'Lau, Yu Lung']",BMC Immunol,,,True
3576b9e0d1895a2d2cb0231304425e1633e86e82,PMC,The Y271 and I274 Amino Acids in Reverse Transcriptase of Human Immunodeficiency Virus-1 Are Critical to Protein Stability,http://dx.doi.org/10.1371/journal.pone.0006108,PMC2701634,19578544,CC BY,"Reverse transcriptase (RT) of human immunodeficiency virus (HIV)-1 plays a key role in initiating viral replication and is an important target for developing anti-HIV drugs. Our previous study showed that two mutations (Y271A and I274A) in the turn RT (Gln(269)-Arg(277)) abrogated viral replication, but the replication capacity and RT activity was discordant. In this study, we further investigated why alanine substitutions at these two sites would affect viral replication. We found that both RT activity and RT protein were almost undetectable in viral particles of these two mutants, although the Pr160(gag-pol) mutants were properly expressed, transported and incorporated. Using protease inhibition assay, we demonstrated a correlation between the degradation of the RT mutants and the activity of viral protease. Our native gel analysis indicated that the mutations at 271 and 274 amino acids might cause conformational changes, leading to the formation of higher order oligomers instead of dimers, resulting in increased protein instability and susceptibility to viral protease. Thus, residues 271 and 274 are critical to RT stability and resistance to viral protease. The conservation of the two amino acid residues among different strains of HIV-1 lent further support to this conclusion. The knowledge gained here may prove useful in drug design.",2009 Jul 3,"['Zhang, Hao-Jie', 'Wang, Yong-Xiang', 'Wu, Hao', 'Jin, Dong-Yan', 'Wen, Yu-Mei', 'Zheng, Bo-Jian']",PLoS One,,,True
d09827278115fad7feb41c47b6da245f54ba1453,PMC,Structure and Inhibition of the SARS Coronavirus Envelope Protein Ion Channel,http://dx.doi.org/10.1371/journal.ppat.1000511,PMC2702000,19593379,CC BY,"The envelope (E) protein from coronaviruses is a small polypeptide that contains at least one α-helical transmembrane domain. Absence, or inactivation, of E protein results in attenuated viruses, due to alterations in either virion morphology or tropism. Apart from its morphogenetic properties, protein E has been reported to have membrane permeabilizing activity. Further, the drug hexamethylene amiloride (HMA), but not amiloride, inhibited in vitro ion channel activity of some synthetic coronavirus E proteins, and also viral replication. We have previously shown for the coronavirus species responsible for severe acute respiratory syndrome (SARS-CoV) that the transmembrane domain of E protein (ETM) forms pentameric α-helical bundles that are likely responsible for the observed channel activity. Herein, using solution NMR in dodecylphosphatidylcholine micelles and energy minimization, we have obtained a model of this channel which features regular α-helices that form a pentameric left-handed parallel bundle. The drug HMA was found to bind inside the lumen of the channel, at both the C-terminal and the N-terminal openings, and, in contrast to amiloride, induced additional chemical shifts in ETM. Full length SARS-CoV E displayed channel activity when transiently expressed in human embryonic kidney 293 (HEK-293) cells in a whole-cell patch clamp set-up. This activity was significantly reduced by hexamethylene amiloride (HMA), but not by amiloride. The channel structure presented herein provides a possible rationale for inhibition, and a platform for future structure-based drug design of this potential pharmacological target.",2009 Jul 10,"['Pervushin, Konstantin', 'Tan, Edward', 'Parthasarathy, Krupakar', 'Lin, Xin', 'Jiang, Feng Li', 'Yu, Dejie', 'Vararattanavech, Ardcharaporn', 'Soong, Tuck Wah', 'Liu, Ding Xiang', 'Torres, Jaume']",PLoS Pathog,,,True
610adc2e0b9fea5bdaa4ea21b46e4bd6b02d558d,PMC,Structure and Inhibition of the SARS Coronavirus Envelope Protein Ion Channel,http://dx.doi.org/10.1371/journal.ppat.1000511,PMC2702000,19593379,CC BY,"The envelope (E) protein from coronaviruses is a small polypeptide that contains at least one α-helical transmembrane domain. Absence, or inactivation, of E protein results in attenuated viruses, due to alterations in either virion morphology or tropism. Apart from its morphogenetic properties, protein E has been reported to have membrane permeabilizing activity. Further, the drug hexamethylene amiloride (HMA), but not amiloride, inhibited in vitro ion channel activity of some synthetic coronavirus E proteins, and also viral replication. We have previously shown for the coronavirus species responsible for severe acute respiratory syndrome (SARS-CoV) that the transmembrane domain of E protein (ETM) forms pentameric α-helical bundles that are likely responsible for the observed channel activity. Herein, using solution NMR in dodecylphosphatidylcholine micelles and energy minimization, we have obtained a model of this channel which features regular α-helices that form a pentameric left-handed parallel bundle. The drug HMA was found to bind inside the lumen of the channel, at both the C-terminal and the N-terminal openings, and, in contrast to amiloride, induced additional chemical shifts in ETM. Full length SARS-CoV E displayed channel activity when transiently expressed in human embryonic kidney 293 (HEK-293) cells in a whole-cell patch clamp set-up. This activity was significantly reduced by hexamethylene amiloride (HMA), but not by amiloride. The channel structure presented herein provides a possible rationale for inhibition, and a platform for future structure-based drug design of this potential pharmacological target.",2009 Jul 10,"['Pervushin, Konstantin', 'Tan, Edward', 'Parthasarathy, Krupakar', 'Lin, Xin', 'Jiang, Feng Li', 'Yu, Dejie', 'Vararattanavech, Ardcharaporn', 'Soong, Tuck Wah', 'Liu, Ding Xiang', 'Torres, Jaume']",PLoS Pathog,,,True
9ad61dcfb0a71ebe88c497995cf569eba5e73f8c,PMC,"Enhancement of the expression of HCV core gene does not enhance core-specific immune response in DNA immunization: advantages of the heterologous DNA prime, protein boost immunization regimen",http://dx.doi.org/10.1186/1479-0556-7-7,PMC2702340,19505299,CC BY,"BACKGROUND: Hepatitis C core protein is an attractive target for HCV vaccine aimed to exterminate HCV infected cells. However, although highly immunogenic in natural infection, core appears to have low immunogenicity in experimental settings. We aimed to design an HCV vaccine prototype based on core, and devise immunization regimens that would lead to potent anti-core immune responses which circumvent the immunogenicity limitations earlier observed. METHODS: Plasmids encoding core with no translation initiation signal (pCMVcore); with Kozak sequence (pCMVcoreKozak); and with HCV IRES (pCMVcoreIRES) were designed and expressed in a variety of eukaryotic cells. Polyproteins corresponding to HCV 1b amino acids (aa) 1–98 and 1–173 were expressed in E. coli. C57BL/6 mice were immunized with four 25-μg doses of pCMVcoreKozak, or pCMV (I). BALB/c mice were immunized with 100 μg of either pCMVcore, or pCMVcoreKozak, or pCMVcoreIRES, or empty pCMV (II). Lastly, BALB/c mice were immunized with 20 μg of core aa 1–98 in prime and boost, or with 100 μg of pCMVcoreKozak in prime and 20 μg of core aa 1–98 in boost (III). Antibody response, [(3)H]-T-incorporation, and cytokine secretion by core/core peptide-stimulated splenocytes were assessed after each immunization. RESULTS: Plasmids differed in core-expression capacity: mouse fibroblasts transfected with pCMVcore, pCMVcoreIRES and pCMVcoreKozak expressed 0.22 ± 0.18, 0.83 ± 0.5, and 13 ± 5 ng core per cell, respectively. Single immunization with highly expressing pCMVcoreKozak induced specific IFN-γ and IL-2, and weak antibody response. Single immunization with plasmids directing low levels of core expression induced similar levels of cytokines, strong T-cell proliferation (pCMVcoreIRES), and antibodies in titer 10(3)(pCMVcore). Boosting with pCMVcoreKozak induced low antibody response, core-specific T-cell proliferation and IFN-γ secretion that subsided after the 3rd plasmid injection. The latter also led to a decrease in specific IL-2 secretion. The best was the heterologous pCMVcoreKozak prime/protein boost regimen that generated mixed Th1/Th2-cellular response with core-specific antibodies in titer ≥ 3 × 10(3). CONCLUSION: Thus, administration of highly expressed HCV core gene, as one large dose or repeated injections of smaller doses, may suppress core-specific immune response. Instead, the latter is induced by a heterologous DNA prime/protein boost regimen that circumvents the negative effects of intracellular core expression.",2009 Jun 8,"['Alekseeva, Ekaterina', 'Sominskaya, Irina', 'Skrastina, Dace', 'Egorova, Irina', 'Starodubova, Elizaveta', 'Kushners, Eriks', 'Mihailova, Marija', 'Petrakova, Natalia', 'Bruvere, Ruta', 'Kozlovskaya, Tatyana', 'Isaguliants, Maria', 'Pumpens, Paul']",Genet Vaccines Ther,,,True
323e747a1a351a6ec4053512e45718fc27d242d3,PMC,The impact on neonatal mortality of shifting childbirth services among levels of hospitals: Taiwan's experience,http://dx.doi.org/10.1186/1472-6963-9-94,PMC2703635,19505330,CC BY,"BACKGROUND: There is considerable discussion surrounding whether advanced hospitals provide better childbirth care than local community hospitals. This study examines the effect of shifting childbirth services from advanced hospitals (i.e., medical centers and regional hospitals) to local community hospitals (i.e., clinics and district hospitals). The sample population was tracked over a seven-year period, which includes the four months of the 2003 severe acute respiratory syndrome (SARS) epidemic in Taiwan. During the SARS epidemic, pregnant women avoided using maternity services in advanced hospitals. Concerns have been raised about maintaining the quality of maternity care with increased demands on childbirth services in local community hospitals. In this study, we analyzed the impact of shifting maternity services among hospitals of different levels on neonatal mortality and maternal deaths. METHODS: A population-based study was conducted using data from Taiwan's National Health Insurance annual statistics of monthly county neonatal morality rates. Based on a pre-SARS sample from January 1998 to December 2002, we estimated a linear regression model which included ""trend,"" a continuous variable representing the effect of yearly changes, and two binary variables, ""month"" and ""county,"" controlling for seasonal and county-specific effects. With the estimated coefficients, we obtained predicted neonatal mortality rates for each county-month. We compared the differences between observed mortality rates of the SARS period and predicted rates to examine whether the shifting in maternity services during the SARS epidemic significantly affected neonatal mortality rates. RESULTS: With an analysis of a total of 1,848 observations between 1998 and 2004, an insignificantly negative mean of standardized predicted errors during the SARS period was found. The result of a sub-sample containing areas with advanced hospitals showed a significant negative mean of standardized predicted errors during the SARS period. These findings indicate that despite increased use of local community hospitals, neonatal mortality during the SARS epidemic did not increase, and even decreased in areas with advanced hospitals. CONCLUSION: An increased use of maternity services in local community hospitals occurred during the SARS epidemic in Taiwan. However, we observed no increase in neonatal and maternity mortality associated with these increased demands on local community hospitals.",2009 Jun 8,"['Wang, Shi-Yi', 'Hsu, Sylvia H', 'Chen, Li-Kuei']",BMC Health Serv Res,,,True
eb49cb90e8f1868b1d73beef301de0ebc481f183,PMC,High-titer preparation of Bombyx mori nucleopolyhedrovirus (BmNPV) displaying recombinant protein in silkworm larvae by size exclusion chromatography and its characterization,http://dx.doi.org/10.1186/1472-6750-9-55,PMC2703641,19523201,CC BY,"BACKGROUND: Budded baculoviruses are utilized for vaccine, the production of antibody and functional analysis of transmembrane proteins. In this study, we tried to produce and purify the recombinant Bombyx mori nucleopolyhedrovirus (rBmNPV-hPRR) that displayed human (pro)renin receptor (hPRR) connected with FLAG peptide sequence on its own surface. These particles were used for further binding analysis of hPRR to human prorenin. The rBmNPV-hPRR was produced in silkworm larvae and purified from its hemolymph using size exclusion chromatography (SEC). RESULTS: A rapid method of BmNPV titer determination in hemolymph was performed using quantitative real-time PCR (Q-PCR). A correlation coefficient of BmNPV determination between end-point dilution and Q-PCR methods was found to be 0.99. rBmNPV-hPRR bacmid-injected silkworm larvae produced recombinant baculovirus of 1.31 × 10(8 )plaque forming unit (pfu) in hemolymph, which was 2.8 × 10(4 )times higher than transfection solution in Bm5 cells. Its purification yield by Sephacryl S-1000 SF column chromatography was 264 fold from larval hemolymph at 4 days post-injection (p.i.), but 35 or 39 fold at 4.5 or 5 days p.i., respectively. Protein patterns of rBmNPV-hPRR purified at 4 and 5 days were the same and ratio of envelope proteins (76, 45 and 35 kDa) to VP39, one of nucleocapsid proteins, increased at 5 days p.i. hPRR was detected in only purified rBmNPV-hPRR at 5 days p.i.. CONCLUSION: The successful purification of rBmNPV-hPRR indicates that baculovirus production using silkworm larvae and its purification from hemolymph by Sephacryl S-1000 SF column chromatography can provide an economical approach in obtaining the purified BmNPV stocks with high titer for large-scale production of hPRR. Also, it can be utilized for further binding analysis and screening of inhibitors of hPRR.",2009 Jun 12,"['Kato, Tatsuya', 'Manoha, Suganthi Lavender', 'Tanaka, Shigeyasu', 'Park, Enoch Y']",BMC Biotechnol,,,True
76dae8b8fd43335310edca09c522640ac9027edf,PMC,Crystal Structure of the C-Terminal Cytoplasmic Domain of Non-Structural Protein 4 from Mouse Hepatitis Virus A59,http://dx.doi.org/10.1371/journal.pone.0006217,PMC2703826,19593433,CC BY,"BACKGROUND: The replication of coronaviruses takes place on cytoplasmic double membrane vesicles (DMVs) originating in the endoplasmic reticulum (ER). Three trans-membrane non-structural proteins, nsp3, nsp4 and nsp6, are understood to be membrane anchors of the coronavirus replication complex. Nsp4 is localized to the ER membrane when expressed alone but is recruited into the replication complex in infected cells. It is revealed to contain four trans-membrane regions and its N- and C-termini are exposed to the cytosol. METHODOLOGY/PRINCIPAL FINDINGS: We have determined the crystal structures of the C-terminal hydrophilic domain of nsp4 (nsp4C) from MHV strain A59 and a C425S site-directed mutant. The highly conserved 89 amino acid region from T408 to Q496 is shown to possess a new fold. The wild-type (WT) structure features two monomers linked by a Cys425-Cys425 disulfide bond in one asymmetric unit. The monomers are arranged with their N- and C-termini in opposite orientations to form an “open” conformation. Mutation of Cys425 to Ser did not affect the monomer structure, although the mutant dimer adopts strikingly different conformations by crystal packing, with the cross-linked C-termini and parallel N-termini of two monomers forming a “closed” conformation. The WT nsp4C exists as a dimer in solution and can dissociate easily into monomers in a reducing environment. CONCLUSIONS/SIGNIFICANCE: As nsp4C is exposed in the reducing cytosol, the monomer of nsp4C should be physiological. This structure may serve as a basis for further functional studies of nsp4.",2009 Jul 10,"['Xu, Xiaoling', 'Lou, Zhiyong', 'Ma, Yanlin', 'Chen, Xuehui', 'Yang, Zhangsheng', 'Tong, Xiaohang', 'Zhao, Qi', 'Xu, Yuanyuan', 'Deng, Hongyu', 'Bartlam, Mark', 'Rao, Zihe']",PLoS One,,,True
a6761d94a9d2827b88e04a42b2e2ddd8036ba410,PMC,CFTR Delivery to 25% of Surface Epithelial Cells Restores Normal Rates of Mucus Transport to Human Cystic Fibrosis Airway Epithelium,http://dx.doi.org/10.1371/journal.pbio.1000155,PMC2705187,19621064,CC0,"Dysfunction of CFTR in cystic fibrosis (CF) airway epithelium perturbs the normal regulation of ion transport, leading to a reduced volume of airway surface liquid (ASL), mucus dehydration, decreased mucus transport, and mucus plugging of the airways. CFTR is normally expressed in ciliated epithelial cells of the surface and submucosal gland ductal epithelium and submucosal gland acinar cells. Critical questions for the development of gene transfer strategies for CF airway disease are what airway regions require CFTR function and how many epithelial cells require CFTR expression to restore normal ASL volume regulation and mucus transport to CF airway epithelium? An in vitro model of human CF ciliated surface airway epithelium (CF HAE) was used to test whether a human parainfluenza virus (PIV) vector engineered to express CFTR (PIVCFTR) could deliver sufficient CFTR to CF HAE to restore mucus transport, thus correcting the CF phenotype. PIVCFTR delivered CFTR to >60% of airway surface epithelial cells and expressed CFTR protein in CF HAE approximately 100-fold over endogenous levels in non-CF HAE. This efficiency of CFTR delivery fully corrected the basic bioelectric defects of Cl(−) and Na(+) epithelial ion transport and restored ASL volume regulation and mucus transport to levels approaching those of non-CF HAE. To determine the numbers of CF HAE surface epithelial cells required to express CFTR for restoration of mucus transport to normal levels, different amounts of PIVCFTR were used to express CFTR in 3%–65% of the surface epithelial cells of CF HAE and correlated to increasing ASL volumes and mucus transport rates. These data demonstrate for the first time, to our knowledge, that restoration of normal mucus transport rates in CF HAE was achieved after CFTR delivery to 25% of surface epithelial cells. In vivo experimentation in appropriate models will be required to determine what level of mucus transport will afford clinical benefit to CF patients, but we predict that a future goal for corrective gene transfer to the CF human airways in vivo would attempt to target at least 25% of surface epithelial cells to achieve mucus transport rates comparable to those in non-CF airways.",2009 Jul 21,"['Zhang, Liqun', 'Button, Brian', 'Gabriel, Sherif E.', 'Burkett, Susan', 'Yan, Yu', 'Skiadopoulos, Mario H.', 'Dang, Yan Li', 'Vogel, Leatrice N.', 'McKay, Tristan', 'Mengos, April', 'Boucher, Richard C.', 'Collins, Peter L.', 'Pickles, Raymond J.']",PLoS Biol,,,True
f4016789973bc61cdb84c457c95e15426e2143b3,PMC,"Occurrence of HSV-1-induced pneumonitis in patients under standard immunosuppressive therapy for rheumatic, vasculitic, and connective tissue disease",http://dx.doi.org/10.1186/1471-2466-9-22,PMC2705343,19450259,CC BY,"BACKGROUND: Herpes simplex virus type-1 (HSV-1) has been described to cause respiratory tract infections in critically ill patients or in individuals that are immunocompromised. It is a continuing matter of debate under which circumstances HSV-1 is a relevant pathogen for pneumonitis. While its role during critical illness has been investigated by prospective interventional studies, comparatively little systematic data is available on the role of HSV-1 for pneumonitis in outpatients with autoimmune disease under a maintenance regimen of immunosuppression. METHODS: We retrospectively reviewed the charts of ~1400 patients with rheumatoid arthritis, vasculitis, and systemic lupus erythematosus (SLE) that were followed at the outpatient clinic of a German University hospital during the years 2000–2007. Episodes of admission to a ward resulting in the diagnosis of pneumonia/pneumonitis were identified, and the type of pneumonia and clinical features retrospectively studied. RESULTS: 63 patients with rheumatoid arthritis, vasculitis, or SLE were admitted to a ward and diagnosed to have pneumonia/pneumonitis. Using bronchoscopy a total of 6 cases of pulmonary infection associated with HSV-1 in the lower respiratory tract were identified. Among those, 2 cases suggested a causative role of HSV-1 as the sole agent causing pneumonitis that proved clinically responsive to antiviral treatment. In the remaining 4 cases HSV-1 appeared as a bystander of bacterial infection. Maintenance therapy with leflunomide, which inhibits HSV-1 assembly in vitro, was associated with a milder course of pneumonitis in one patient. Detection of HSV-1 was associated with stronger immunosuppressive regimens and vasculitic disease. CONCLUSION: The present study analyzed the frequency and hallmarks of cases of HSV-1 associated pneumonitis that occurred in a comparatively large cohort of patients with rheumatologic autoimmune diseases. In an area of controversy, this study provides further evidence that HSV-1 causes isolated pneumonitis in the immunocompromised. The study may provide an estimate on the frequency of relevant HSV-1 infection and bacterial agents in outpatients with autoimmune disease.",2009 May 18,"['Witt, Matthias N', 'Braun, Gerald S', 'Ihrler, Stephan', 'Schmid, Holger']",BMC Pulm Med,,,True
4395141eef1089f1c75a14912fade412fd694c19,PMC,"Studies on membrane topology, N-glycosylation and functionality of SARS-CoV membrane protein",http://dx.doi.org/10.1186/1743-422X-6-79,PMC2705359,19534833,CC BY,"The glycosylated membrane protein M of the severe acute respiratory syndrome associated coronavirus (SARS-CoV) is the main structural component of the virion and mediates assembly and budding of viral particles. The membrane topology of SARS-CoV M and the functional significance of its N-glycosylation are not completely understood as is its interaction with the surface glycoprotein S. Using biochemical and immunofluorescence analyses we found that M consists of a short glycosylated N-terminal ectodomain, three transmembrane segments and a long, immunogenic C-terminal endodomain. Although the N-glycosylation site of M seems to be highly conserved between group 1 and 3 coronaviruses, studies using a recombinant SARS-CoV expressing a glycosylation-deficient M revealed that N-glycosylation of M neither influence the shape of the virions nor their infectivity in cell culture. Further functional analysis of truncated M proteins showed that the N-terminal 134 amino acids comprising the three transmembrane domains are sufficient to mediate accumulation of M in the Golgi complex and to enforce recruitment of the viral spike protein S to the sites of virus assembly and budding in the ERGIC.",2009 Jun 18,"['Voß, Daniel', 'Pfefferle, Susanne', 'Drosten, Christian', 'Stevermann, Lea', 'Traggiai, Elisabetta', 'Lanzavecchia, Antonio', 'Becker, Stephan']",Virol J,,,True
9becd2019e0ff5052d47d3d23201cc521375cb03,PMC,Toward unsupervised outbreak detection through visual perception of new patterns,http://dx.doi.org/10.1186/1471-2458-9-179,PMC2706246,19515246,CC BY,"BACKGROUND: Statistical algorithms are routinely used to detect outbreaks of well-defined syndromes, such as influenza-like illness. These methods cannot be applied to the detection of emerging diseases for which no preexisting information is available. This paper presents a method aimed at facilitating the detection of outbreaks, when there is no a priori knowledge of the clinical presentation of cases. METHODS: The method uses a visual representation of the symptoms and diseases coded during a patient consultation according to the International Classification of Primary Care 2(nd )version (ICPC-2). The surveillance data are transformed into color-coded cells, ranging from white to red, reflecting the increasing frequency of observed signs. They are placed in a graphic reference frame mimicking body anatomy. Simple visual observation of color-change patterns over time, concerning a single code or a combination of codes, enables detection in the setting of interest. RESULTS: The method is demonstrated through retrospective analyses of two data sets: description of the patients referred to the hospital by their general practitioners (GPs) participating in the French Sentinel Network and description of patients directly consulting at a hospital emergency department (HED). Informative image color-change alert patterns emerged in both cases: the health consequences of the August 2003 heat wave were visualized with GPs' data (but passed unnoticed with conventional surveillance systems), and the flu epidemics, which are routinely detected by standard statistical techniques, were recognized visually with HED data. CONCLUSION: Using human visual pattern-recognition capacities to detect the onset of unexpected health events implies a convenient image representation of epidemiological surveillance and well-trained ""epidemiology watchers"". Once these two conditions are met, one could imagine that the epidemiology watchers could signal epidemiological alerts, based on ""image walls"" presenting the local, regional and/or national surveillance patterns, with specialized field epidemiologists assigned to validate the signals detected.",2009 Jun 10,"['Lévy, Pierre P', 'Valleron, Alain-Jacques']",BMC Public Health,,,True
049294a884d39102b06a634ba0f4bd3185fcc478,PMC,"Klassevirus 1, a previously undescribed member of the family Picornaviridae, is globally widespread",http://dx.doi.org/10.1186/1743-422X-6-86,PMC2706813,19552824,CC BY,"BACKGROUND: Diarrhea is the third leading infectious cause of death worldwide and is estimated to be responsible for approximately 2 million deaths a year. While many infectious causes of diarrhea have been established, approximately 40% of all diarrhea cases are of unknown etiology. In an effort to identify novel viruses that may be causal agents of diarrhea, we used high throughput mass sequencing to analyze stool samples collected from patients with acute diarrhea. RESULTS: Sequences with limited similarity to known picornaviruses were detected in a stool sample collected in Australia from a child with acute diarrhea. Using a combination of mass sequencing, RT-PCR, 5' RACE and 3' RACE, a 6383 bp fragment of the viral genome was sequenced. Phylogenetic analysis demonstrated that this virus was highly divergent from, but most closely related to, members of the genus Kobuvirus. We have tentatively named this novel virus klassevirus 1. We also detected klassevirus 1 by RT-PCR in a diarrhea specimen collected from a patient in St. Louis, United States as well as in untreated sewage collected in Barcelona, Spain. CONCLUSION: Klassevirus 1 is a previously undescribed picornavirus that is globally widespread and present on at least three continents. Further investigations to determine whether klassevirus 1 is a human pathogen are needed.",2009 Jun 24,"['Holtz, Lori R', 'Finkbeiner, Stacy R', 'Zhao, Guoyan', 'Kirkwood, Carl D', 'Girones, Rosina', 'Pipas, James M', 'Wang, David']",Virol J,,,True
63205fe99a388f19fde06f422c9ce6c1ddfc52f4,PMC,"Remission of Invasive, Cancer Stem-Like Glioblastoma Xenografts Using Lentiviral Vector-Mediated Suicide Gene Therapy",http://dx.doi.org/10.1371/journal.pone.0006314,PMC2707627,19617915,CC BY,"BACKGROUND: Glioblastoma is the most frequent and most malignant primary brain tumor with a poor prognosis. The translation of therapeutic strategies for glioblastoma from the experimental phase into the clinic has been limited by insufficient animal models, which lack important features of human tumors. Lentiviral gene therapy is an attractive therapeutic option for human glioblastoma, which we validated in a clinically relevant animal model. METHODOLOGY/PRINCIPAL FINDINGS: We used a rodent xenograft model that recapitulates the invasive and angiogenic features of human glioblastoma to analyze the transduction pattern and therapeutic efficacy of lentiviral pseudotyped vectors. Both, lymphocytic choriomeningitis virus glycoprotein (LCMV-GP) and vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentiviral vectors very efficiently transduced human glioblastoma cells in vitro and in vivo. In contrast, pseudotyped gammaretroviral vectors, similar to those evaluated for clinical therapy of glioblastoma, showed inefficient gene transfer in vitro and in vivo. Both pseudotyped lentiviral vectors transduced cancer stem-like cells characterized by their CD133-, nestin- and SOX2-expression, the ability to form spheroids in neural stem cell medium and to express astrocytic and neuronal differentiation markers under serum conditions. In a therapeutic approach using the suicide gene herpes simplex virus thymidine kinase (HSV-1-tk) fused to eGFP, both lentiviral vectors mediated a complete remission of solid tumors as seen on MRI resulting in a highly significant survival benefit (p<0.001) compared to control groups. In all recurrent tumors, surviving eGFP-positive tumor cells were found, advocating prodrug application for several cycles to even enhance and prolong the therapeutic effect. CONCLUSIONS/SIGNIFICANCE: In conclusion, lentiviral pseudotyped vectors are promising candidates for gene therapy of glioma in patients. The inefficient gene delivery by gammaretroviral vectors is in line with the results obtained in clinical therapy for GBM and thus confirms the high reproducibility of the invasive glioma animal model for translational research.",2009 Jul 20,"['Huszthy, Peter C.', 'Giroglou, Tsanan', 'Tsinkalovsky, Oleg', 'Euskirchen, Philipp', 'Skaftnesmo, Kai Ove', 'Bjerkvig, Rolf', 'von Laer, Dorothee', 'Miletic, Hrvoje']",PLoS One,,,True
d0ce640c27c2c8ef5f83e71bec07d829327d69d6,PMC,Protein Never in Mitosis Gene A Interacting-1 regulates calpain activity and the degradation of cyclooxygenase-2 in endothelial cells,http://dx.doi.org/10.1186/1476-9255-6-20,PMC2708161,19545424,CC BY,"BACKGROUND: The peptidyl-proline isomerase, Protein Never in Mitosis Gene A Interacting-1 (PIN1), regulates turnover of inducible nitric oxide synthase (iNOS) in murine aortic endothelial cells (MAEC) stimulated with E. coli endotoxin (LPS) and interferon-γ (IFN). Degradation of iNOS was reduced by a calpain inhibitor, suggesting that PIN1 may affect induction of other calpain-sensitive inflammatory proteins, such as cyclooxygenase (COX)-2, in MAEC. METHODS: MAEC, transduced with lentivirus encoding an inactive control short hairpin (sh) RNA or one targeting PIN1 that reduced PIN1 by 85%, were used. Cells were treated with LPS/IFN, calpain inhibitors (carbobenzoxy-valinyl-phenylalaninal (zVF), PD150606), cycloheximide and COX inhibitors to determine the effect of PIN1 depletion on COX-2 and calpain. RESULTS: LPS or IFN alone did not induce COX-2. However, treatment with 10 μg LPS plus 20 ng IFN per ml induced COX-2 protein 10-fold in Control shRNA MAEC. Induction was significantly greater (47-fold) in PIN1 shRNA cells. COX-2-dependent prostaglandin E2 production increased 3-fold in KD MAEC, but did not increase in Control cells. The additional increase in COX-2 protein due to PIN1 depletion was post-transcriptional, as induction of COX-2 mRNA by LPS/IFN was the same in cells containing or lacking PIN1. Instead, the loss of COX-2 protein, after treatment with cycloheximide to block protein synthesis, was reduced in cells lacking PIN1 in comparison with Control cells, indicating that degradation of the enzyme was reduced. zVF and PD150606 each enhanced the induction of COX-2 by LPS/IFN. zVF also slowed the loss of COX-2 after treatment with cycloheximide, and COX-2 was degraded by exogenous μ-calpain in vitro. In contrast to iNOS, physical interaction between COX-2 and PIN1 was not detected, suggesting that effects of PIN1 on calpain, rather than COX-2 itself, affect COX-2 degradation. While cathepsin activity was unaltered, depletion of PIN1 reduced calpain activity by 55% in comparison with Control shRNA cells. CONCLUSION: PIN1 reduced calpain activity and slowed the degradation of COX-2 in MAEC, an effect recapitulated by an inhibitor of calpain. Given the sensitivity of COX-2 and iNOS to calpain, PIN1 may normally limit induction of these and other calpain substrates by maintaining calpain activity in endothelial cells.",2009 Jun 22,"['Liu, Tongzheng', 'Schneider, Ryan A', 'Shah, Vaibhav', 'Huang, Yongcheng', 'Likhotvorik, Rostislav I', 'Keshvara, Lakhu', 'Hoyt, Dale G']",J Inflamm (Lond),,,True
b15e513ac2f5696b1e51324fb0a3118c44a6a9e9,PMC,Models of epidemics: when contact repetition and clustering should be included,http://dx.doi.org/10.1186/1742-4682-6-11,PMC2709892,19563624,CC BY,"BACKGROUND: The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. METHODS: We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. RESULTS: The simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. CONCLUSION: We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.",2009 Jun 29,"['Smieszek, Timo', 'Fiebig, Lena', 'Scholz, Roland W']",Theor Biol Med Model,,,True
2b4187e81b56790a8c7390d631eb8081c0ab5c2b,PMC,Models of epidemics: when contact repetition and clustering should be included,http://dx.doi.org/10.1186/1742-4682-6-11,PMC2709892,19563624,CC BY,"BACKGROUND: The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. METHODS: We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. RESULTS: The simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. CONCLUSION: We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.",2009 Jun 29,"['Smieszek, Timo', 'Fiebig, Lena', 'Scholz, Roland W']",Theor Biol Med Model,,,False
d0235ece6d613b700d5c4b369eaecb2dc81e5168,PMC,Models of epidemics: when contact repetition and clustering should be included,http://dx.doi.org/10.1186/1742-4682-6-11,PMC2709892,19563624,CC BY,"BACKGROUND: The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. METHODS: We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. RESULTS: The simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. CONCLUSION: We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.",2009 Jun 29,"['Smieszek, Timo', 'Fiebig, Lena', 'Scholz, Roland W']",Theor Biol Med Model,,,False
86a5eec529af27298f88a24a32561946cb2e8f8d,PMC,Models of epidemics: when contact repetition and clustering should be included,http://dx.doi.org/10.1186/1742-4682-6-11,PMC2709892,19563624,CC BY,"BACKGROUND: The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. METHODS: We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. RESULTS: The simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. CONCLUSION: We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.",2009 Jun 29,"['Smieszek, Timo', 'Fiebig, Lena', 'Scholz, Roland W']",Theor Biol Med Model,,,False
754eb3d52a722efaeee91ef19bba2d5c62fe0eae,PMC,Models of epidemics: when contact repetition and clustering should be included,http://dx.doi.org/10.1186/1742-4682-6-11,PMC2709892,19563624,CC BY,"BACKGROUND: The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. METHODS: We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. RESULTS: The simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. CONCLUSION: We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.",2009 Jun 29,"['Smieszek, Timo', 'Fiebig, Lena', 'Scholz, Roland W']",Theor Biol Med Model,,,False
82f3e5abcabd0756aae8c054832a80658915bde3,PMC,Rapid and High-Throughput pan-Orthopoxvirus Detection and Identification using PCR and Mass Spectrometry,http://dx.doi.org/10.1371/journal.pone.0006342,PMC2710004,19623263,CC BY,"The genus Orthopoxvirus contains several species of related viruses, including the causative agent of smallpox (Variola virus). In addition to smallpox, several other members of the genus are capable of causing human infection, including monkeypox, cowpox, and other zoonotic rodent-borne poxviruses. Therefore, a single assay that can accurately identify all orthopoxviruses could provide a valuable tool for rapid broad orthopovirus identification. We have developed a pan-Orthopoxvirus assay for identification of all members of the genus based on four PCR reactions targeting Orthopoxvirus DNA and RNA helicase and polymerase genes. The amplicons are detected using electrospray ionization-mass spectrometry (PCR/ESI-MS) on the Ibis T5000 system. We demonstrate that the assay can detect and identify a diverse collection of orthopoxviruses, provide sub-species information and characterize viruses from the blood of rabbitpox infected rabbits. The assay is sensitive at the stochastic limit of PCR and detected virus in blood containing approximately six plaque-forming units per milliliter from a rabbitpox virus-infected rabbit.",2009 Jul 22,"['Eshoo, Mark W.', 'Whitehouse, Chris A.', 'Nalca, Aysegul', 'Zoll, Scott', 'Ecker, Joseph A.', 'Hall, Thomas A.', 'Pennella, Thuy-Trang D.', 'Duncan, David D.', 'Desai, Anjali', 'Moradi, Emily K.', 'Rudnick, Karl', 'Libby, Brian', 'Ranken, Raymond', 'Sampath, Rangarajan', 'Hofstadler, Steven A.', 'Ecker, David J.', 'Blyn, Lawrence B.']",PLoS One,,,True
49b325fc505d265149ed0c2e9131662626c16939,PMC,Pandemic influenza: implications for occupational medicine,http://dx.doi.org/10.1186/1745-6673-4-15,PMC2710320,19549302,CC BY,"This article reviews the biological and occupational medicine literature related to H5N1 pandemic influenza and its impact on infection control, cost and business continuity in settings outside the health care community. The literature on H5N1 biology is reviewed including the treatment and infection control mechanisms as they pertain to occupational medicine. Planning activity for the potential arrival of pandemic avian influenza is growing rapidly. Much has been published on the molecular biology of H5N1 but there remains a paucity of literature on the occupational medicine impacts to organizations. This review summarizes some of the basic science surrounding H5N1 influenza and raises some key concerns in pandemic planning for the occupational medicine professional. Workplaces other than health care settings will be impacted greatly by an H5N1 pandemic and the occupational physician will play an essential role in corporate preparation, response, and business continuity strategies.",2009 Jun 23,"['Journeay, W Shane', 'Burnstein, Matthew D']",J Occup Med Toxicol,,,True
8d095d0275e474dbb9d9b63a75591ff2c0667d73,PMC,Evidence of Recombination and Genetic Diversity in Human Rhinoviruses in Children with Acute Respiratory Infection,http://dx.doi.org/10.1371/journal.pone.0006355,PMC2712091,19633719,CC BY,"BACKGROUND: Human rhinoviruses (HRVs) are a highly prevalent cause of acute respiratory infection in children. They are classified into at least three species, HRV-A, HRV-B and HRV-C, which are characterized by sequencing the 5′ untranslated region (UTR) or the VP4/VP2 region of the genome. Given the increased interest for novel HRV strain identification and their worldwide distribution, we have carried out clinical and molecular diagnosis of HRV strains in a 2-year study of children with acute respiratory infection visiting one district hospital in Shanghai. METHODOLOGY/FINDINGS: We cloned and sequenced a 924-nt fragment that covered part of the 5′UTR and the VP4/VP2 capsid genes. Sixty-four HRV-infected outpatients were diagnosed amongst 827 children with acute low respiratory tract infection. Two samples were co-infected with HRV-A and HRV-B or HRV-C. By comparative analysis of the VP4/VP2 sequences of the 66 HRVs, we showed a high diversity of strains in HRV-A and HRV-B species, and a prevalence of 51.5% of strains that belonged to the recently identified HRV-C species. When analyzing a fragment of the 5′ UTR, we characterized at least two subspecies of HRV-C: HRV-Cc, which clustered differently from HRV-A and HRV-B, and HRV-Ca, which resulted from previous recombination in this region with sequences related to HRV-A. The full-length sequence of one strain of each HRV-Ca and HRV-Cc subspecies was obtained for comparative analysis. We confirmed the close relationship of their structural proteins but showed apparent additional recombination events in the 2A gene and 3′UTR of the HRV-Ca strain. Double or triple infections with HRV-C and respiratory syncytial virus and/or bocavirus were diagnosed in 33.3% of the HRV-infected patients, but no correlation with severity of clinical outcome was observed. CONCLUSION: Our study showed a high diversity of HRV strains that cause bronchitis and pneumonia in children. A predominance of HRV-C over HRV-A and HRV-B was observed, and two subspecies of HRV-C were identified, the diversity of which seemed to be related to recombination with former HRV-A strains. None of the HRV-C strains appeared to have a higher clinical impact than HRV-A or HRV-B on respiratory compromise.",2009 Jul 27,"['Huang, Ting', 'Wang, Wei', 'Bessaud, Mael', 'Ren, Peijun', 'Sheng, Jun', 'Yan, Huajie', 'Zhang, Jing', 'Lin, Xin', 'Wang, Yongjin', 'Delpeyroux, Francis', 'Deubel, Vincent']",PLoS One,,,True
f415c477bac80d18eec2b6775efd8d660a7688ba,PMC,Novel Mechanistic Insights into Viral Modulation of Immune Receptor Signaling,http://dx.doi.org/10.1371/journal.ppat.1000404,PMC2712764,19649322,CC BY,,2009 Jul 31,"Sigalov, Alexander B.",PLoS Pathog,,,True
347d44e7849c7abbf867722925ffc5996b0f9a11,PMC,Influence of Dendritic Cells on Viral Pathogenicity,http://dx.doi.org/10.1371/journal.ppat.1000384,PMC2712770,19649323,CC BY,"Although most viral infections cause minor, if any, symptoms, a certain number result in serious illness. Viral disease symptoms result both from direct viral replication within host cells and from indirect immunopathological consequences. Dendritic cells (DCs) are key determinants of viral disease outcome; they activate immune responses during viral infection and direct T cells toward distinct T helper type responses. Certain viruses are able to skew cytokine secretion by DCs inducing and/or downregulating the immune system with the aim of facilitating and prolonging release of progeny. Thus, the interaction of DCs with viruses most often results in the absence of disease or complete recovery when natural functions of DCs prevail, but may lead to chronic illness or death when these functions are outmanoeuvred by viruses in the exploitation of DCs.",2009 Jul 31,"['Freer, Giulia', 'Matteucci, Donatella']",PLoS Pathog,,,True
baa419d7be9ab01f85ff19c108df77103b29cb50,PMC,Constitutional Flavonoids Derived from Epimedium Dose-Dependently Reduce Incidence of Steroid-Associated Osteonecrosis Not via Direct Action by Themselves on Potential Cellular Targets,http://dx.doi.org/10.1371/journal.pone.0006419,PMC2713419,19641620,CC BY,"Intravascular-thrombosis and extravascular-lipid-deposit are the two key pathogenic events considered to interrupt intraosseous blood supply during development of steroid-associated osteonecrosis (ON). However, there are no clinically employed agents capable of simultaneously targeting these two key pathogenic events. The present experimental study demonstrated that constitutional flavonoid glycosides derived from herb Epimedium (EF, composed of seven flavonoid compounds with common stem nuclear) exerted dose-dependent effect on inhibition of both thrombosis and lipid-deposition and accordingly reducing incidence of steroid-associated ON in rabbits, which was not via direct action by themselves rather by their common metabolite on potential cellular targets involved in the two pathogenic pathways. The underlying mechanism could be explained by counteracting endothelium injury and excessive adipogenesis. These findings encourage designing clinical trials to investigate potential of EF in prevention of steroid-associated ON.",2009 Jul 29,"['Zhang, Ge', 'Wang, Xin-Luan', 'Sheng, Hui', 'Xie, Xin-Hui', 'He, Yi-Xin', 'Yao, Xin-Sheng', 'Li, Zi-Rong', 'Lee, Kwong-Man', 'He, Wei', 'Leung, Kwok-Sui', 'Qin, Ling']",PLoS One,,,True
8ef0cd02635a7841b2b26cb159038427c31c39b3,PMC,Is dengue a threat to the blood supply?,http://dx.doi.org/10.1111/j.1365-3148.2009.00916.x,PMC2713854,19392949,CC BY,"Dengue is the most common arthropod-borne infection worldwide, affecting at least 50 million people every year and endemic in more than 100 countries. The dengue virus is a single-stranded RNA virus with four major serotypes. Infection with one serotype confers homotypic immunity but not heterologous immunity, and secondary infection with another serotype may lead to more severe disease. The major route of transmission occurs through the Aedes aegypti mosquito vector, but dengue has also been transmitted through blood transfusion and organ transplantation. Infection results in a spectrum of clinical illness ranging from asymptomatic infection, undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF) to dengue shock syndrome (DSS). Dengue is spreading rapidly to new areas and with increasing frequency of major outbreaks. A trend has also been observed towards increasing age among infected patients. This will impact blood supply availability as more blood donors are deferred because of dengue infection or exposure to infection. The risk of transmission through transfusion of blood from asymptomatic viraemic donors will also increase. Although screening tests for dengue and effective pathogen reduction processes are now available for the blood supply, the value of implementing these costly measures needs to be carefully considered. Demand for platelets and fresh frozen plasma will rise with increasing number of DHF/DSS. Evidence-based guidelines for the clinical use of these blood components in the management of patients with DHF/DSS have not been well established, and inappropriate use will contribute to the challenges faced by blood services.",2009 Apr,"['Teo, D', 'Ng, L C', 'Lam, S']",Transfus Med,,,True
f318f02676fa086210640feb3fb488ae9522ba95,PMC,Structure of the C-terminal domain of nsp4 from feline coronavirus,http://dx.doi.org/10.1107/S0907444909018253,PMC2714721,19622868,CC BY,"Coronaviruses are a family of positive-stranded RNA viruses that includes important pathogens of humans and other animals. The large coronavirus genome (26–31 kb) encodes 15–16 nonstructural proteins (nsps) that are derived from two replicase polyproteins by autoproteolytic processing. The nsps assemble into the viral replication–transcription complex and nsp3, nsp4 and nsp6 are believed to anchor this enzyme complex to modified intracellular membranes. The largest part of the coronavirus nsp4 subunit is hydrophobic and is predicted to be embedded in the membranes. In this report, a conserved C-terminal domain (∼100 amino-acid residues) has been delineated that is predicted to face the cytoplasm and has been isolated as a soluble domain using library-based construct screening. A prototypical crystal structure at 2.8 Å resolution was obtained using nsp4 from feline coronavirus. Unmodified and SeMet-substituted proteins were crystallized under similar conditions, resulting in tetragonal crystals that belonged to space group P4(3). The phase problem was initially solved by single isomorphous replacement with anomalous scattering (SIRAS), followed by molecular replacement using a SIRAS-derived composite model. The structure consists of a single domain with a predominantly α-helical content displaying a unique fold that could be engaged in protein–protein interactions.",2009 Aug 1,"['Manolaridis, Ioannis', 'Wojdyla, Justyna A.', 'Panjikar, Santosh', 'Snijder, Eric J.', 'Gorbalenya, Alexander E.', 'Berglind, Hanna', 'Nordlund, Pär', 'Coutard, Bruno', 'Tucker, Paul A.']",Acta Crystallogr D Biol Crystallogr,,,True
e296fa71274bad6cabcf683a2ba47e58b1326877,PMC,Musings on privacy issues in health research involving disaggregate geographic data about individuals,http://dx.doi.org/10.1186/1476-072X-8-46,PMC2716332,19619311,CC BY,"This paper offers a state-of-the-art overview of the intertwined privacy, confidentiality, and security issues that are commonly encountered in health research involving disaggregate geographic data about individuals. Key definitions are provided, along with some examples of actual and potential security and confidentiality breaches and related incidents that captured mainstream media and public interest in recent months and years. The paper then goes on to present a brief survey of the research literature on location privacy/confidentiality concerns and on privacy-preserving solutions in conventional health research and beyond, touching on the emerging privacy issues associated with online consumer geoinformatics and location-based services. The 'missing ring' (in many treatments of the topic) of data security is also discussed. Personal information and privacy legislations in two countries, Canada and the UK, are covered, as well as some examples of recent research projects and events about the subject. Select highlights from a June 2009 URISA (Urban and Regional Information Systems Association) workshop entitled 'Protecting Privacy and Confidentiality of Geographic Data in Health Research' are then presented. The paper concludes by briefly charting the complexity of the domain and the many challenges associated with it, and proposing a novel, 'one stop shop' case-based reasoning framework to streamline the provision of clear and individualised guidance for the design and approval of new research projects (involving geographical identifiers about individuals), including crisp recommendations on which specific privacy-preserving solutions and approaches would be suitable in each case.",2009 Jul 20,"['Boulos, Maged N Kamel', 'Curtis, Andrew J', 'AbdelMalik, Philip']",Int J Health Geogr,,,True
b00ed3b8efc4531b84e5035419418056eea0799b,PMC,Musings on privacy issues in health research involving disaggregate geographic data about individuals,http://dx.doi.org/10.1186/1476-072X-8-46,PMC2716332,19619311,CC BY,"This paper offers a state-of-the-art overview of the intertwined privacy, confidentiality, and security issues that are commonly encountered in health research involving disaggregate geographic data about individuals. Key definitions are provided, along with some examples of actual and potential security and confidentiality breaches and related incidents that captured mainstream media and public interest in recent months and years. The paper then goes on to present a brief survey of the research literature on location privacy/confidentiality concerns and on privacy-preserving solutions in conventional health research and beyond, touching on the emerging privacy issues associated with online consumer geoinformatics and location-based services. The 'missing ring' (in many treatments of the topic) of data security is also discussed. Personal information and privacy legislations in two countries, Canada and the UK, are covered, as well as some examples of recent research projects and events about the subject. Select highlights from a June 2009 URISA (Urban and Regional Information Systems Association) workshop entitled 'Protecting Privacy and Confidentiality of Geographic Data in Health Research' are then presented. The paper concludes by briefly charting the complexity of the domain and the many challenges associated with it, and proposing a novel, 'one stop shop' case-based reasoning framework to streamline the provision of clear and individualised guidance for the design and approval of new research projects (involving geographical identifiers about individuals), including crisp recommendations on which specific privacy-preserving solutions and approaches would be suitable in each case.",2009 Jul 20,"['Boulos, Maged N Kamel', 'Curtis, Andrew J', 'AbdelMalik, Philip']",Int J Health Geogr,,,True
dcf12f1f76ae03b3107f00aadea540298105d312,PMC,Temporal Variability and Social Heterogeneity in Disease Transmission: The Case of SARS in Hong Kong,http://dx.doi.org/10.1371/journal.pcbi.1000471,PMC2717369,19696879,CC BY,"The extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. This study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. The 2002–2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong, where 27% of cases were healthcare workers, was used as an example. A stochastic compartmental SEIR (susceptible-exposed-infectious-removed) model was used: the population was split into healthcare workers, hospitalized people and general population. Super spreading events (SSEs) were taken into account in the model. The temporal evolutions of the daily effective contact rates in the community and hospitals were modeled with smooth functions. Data augmentation techniques and Markov chain Monte Carlo (MCMC) methods were applied to estimate SARS epidemiological parameters. In particular, estimates of daily reproduction numbers were provided for each subpopulation. The average duration of the SARS infectious period was estimated to be 9.3 days (±0.3 days). The model was able to disentangle the impact of the two SSEs from background transmission rates. The effective contact rates, which were estimated on a daily basis, decreased with time, reaching zero inside hospitals. This observation suggests that public health measures and possible changes in individual behaviors effectively reduced transmission, especially in hospitals. The temporal patterns of reproduction numbers were similar for healthcare workers and the general population, indicating that on average, an infectious healthcare worker did not infect more people than any other infectious person. We provide a general method to estimate time dependence of parameters in structured epidemic models, which enables investigation of the impact of control measures and behavioral changes in different settings.",2009 Aug 21,"['Cori, Anne', 'Boëlle, Pierre-Yves', 'Thomas, Guy', 'Leung, Gabriel M.', 'Valleron, Alain-Jacques']",PLoS Comput Biol,,,True
1f47ecc5657834cf9676ecdfd1f3f170b204b9c0,PMC,Temporal Variability and Social Heterogeneity in Disease Transmission: The Case of SARS in Hong Kong,http://dx.doi.org/10.1371/journal.pcbi.1000471,PMC2717369,19696879,CC BY,"The extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. This study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. The 2002–2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong, where 27% of cases were healthcare workers, was used as an example. A stochastic compartmental SEIR (susceptible-exposed-infectious-removed) model was used: the population was split into healthcare workers, hospitalized people and general population. Super spreading events (SSEs) were taken into account in the model. The temporal evolutions of the daily effective contact rates in the community and hospitals were modeled with smooth functions. Data augmentation techniques and Markov chain Monte Carlo (MCMC) methods were applied to estimate SARS epidemiological parameters. In particular, estimates of daily reproduction numbers were provided for each subpopulation. The average duration of the SARS infectious period was estimated to be 9.3 days (±0.3 days). The model was able to disentangle the impact of the two SSEs from background transmission rates. The effective contact rates, which were estimated on a daily basis, decreased with time, reaching zero inside hospitals. This observation suggests that public health measures and possible changes in individual behaviors effectively reduced transmission, especially in hospitals. The temporal patterns of reproduction numbers were similar for healthcare workers and the general population, indicating that on average, an infectious healthcare worker did not infect more people than any other infectious person. We provide a general method to estimate time dependence of parameters in structured epidemic models, which enables investigation of the impact of control measures and behavioral changes in different settings.",2009 Aug 21,"['Cori, Anne', 'Boëlle, Pierre-Yves', 'Thomas, Guy', 'Leung, Gabriel M.', 'Valleron, Alain-Jacques']",PLoS Comput Biol,,,False
933a1b843db9eb0d98835f9359622ba8cb8bdc05,PMC,Temporal Variability and Social Heterogeneity in Disease Transmission: The Case of SARS in Hong Kong,http://dx.doi.org/10.1371/journal.pcbi.1000471,PMC2717369,19696879,CC BY,"The extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. This study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. The 2002–2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong, where 27% of cases were healthcare workers, was used as an example. A stochastic compartmental SEIR (susceptible-exposed-infectious-removed) model was used: the population was split into healthcare workers, hospitalized people and general population. Super spreading events (SSEs) were taken into account in the model. The temporal evolutions of the daily effective contact rates in the community and hospitals were modeled with smooth functions. Data augmentation techniques and Markov chain Monte Carlo (MCMC) methods were applied to estimate SARS epidemiological parameters. In particular, estimates of daily reproduction numbers were provided for each subpopulation. The average duration of the SARS infectious period was estimated to be 9.3 days (±0.3 days). The model was able to disentangle the impact of the two SSEs from background transmission rates. The effective contact rates, which were estimated on a daily basis, decreased with time, reaching zero inside hospitals. This observation suggests that public health measures and possible changes in individual behaviors effectively reduced transmission, especially in hospitals. The temporal patterns of reproduction numbers were similar for healthcare workers and the general population, indicating that on average, an infectious healthcare worker did not infect more people than any other infectious person. We provide a general method to estimate time dependence of parameters in structured epidemic models, which enables investigation of the impact of control measures and behavioral changes in different settings.",2009 Aug 21,"['Cori, Anne', 'Boëlle, Pierre-Yves', 'Thomas, Guy', 'Leung, Gabriel M.', 'Valleron, Alain-Jacques']",PLoS Comput Biol,,,True
d7a89e6c00e3e927a2c521c347629fcc0950a5d6,PMC,Temporal Variability and Social Heterogeneity in Disease Transmission: The Case of SARS in Hong Kong,http://dx.doi.org/10.1371/journal.pcbi.1000471,PMC2717369,19696879,CC BY,"The extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. This study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. The 2002–2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong, where 27% of cases were healthcare workers, was used as an example. A stochastic compartmental SEIR (susceptible-exposed-infectious-removed) model was used: the population was split into healthcare workers, hospitalized people and general population. Super spreading events (SSEs) were taken into account in the model. The temporal evolutions of the daily effective contact rates in the community and hospitals were modeled with smooth functions. Data augmentation techniques and Markov chain Monte Carlo (MCMC) methods were applied to estimate SARS epidemiological parameters. In particular, estimates of daily reproduction numbers were provided for each subpopulation. The average duration of the SARS infectious period was estimated to be 9.3 days (±0.3 days). The model was able to disentangle the impact of the two SSEs from background transmission rates. The effective contact rates, which were estimated on a daily basis, decreased with time, reaching zero inside hospitals. This observation suggests that public health measures and possible changes in individual behaviors effectively reduced transmission, especially in hospitals. The temporal patterns of reproduction numbers were similar for healthcare workers and the general population, indicating that on average, an infectious healthcare worker did not infect more people than any other infectious person. We provide a general method to estimate time dependence of parameters in structured epidemic models, which enables investigation of the impact of control measures and behavioral changes in different settings.",2009 Aug 21,"['Cori, Anne', 'Boëlle, Pierre-Yves', 'Thomas, Guy', 'Leung, Gabriel M.', 'Valleron, Alain-Jacques']",PLoS Comput Biol,,,False
5a55cfceb7365142481967c11c4f70b359a1e4b1,PMC,Temporal Variability and Social Heterogeneity in Disease Transmission: The Case of SARS in Hong Kong,http://dx.doi.org/10.1371/journal.pcbi.1000471,PMC2717369,19696879,CC BY,"The extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. This study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. The 2002–2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong, where 27% of cases were healthcare workers, was used as an example. A stochastic compartmental SEIR (susceptible-exposed-infectious-removed) model was used: the population was split into healthcare workers, hospitalized people and general population. Super spreading events (SSEs) were taken into account in the model. The temporal evolutions of the daily effective contact rates in the community and hospitals were modeled with smooth functions. Data augmentation techniques and Markov chain Monte Carlo (MCMC) methods were applied to estimate SARS epidemiological parameters. In particular, estimates of daily reproduction numbers were provided for each subpopulation. The average duration of the SARS infectious period was estimated to be 9.3 days (±0.3 days). The model was able to disentangle the impact of the two SSEs from background transmission rates. The effective contact rates, which were estimated on a daily basis, decreased with time, reaching zero inside hospitals. This observation suggests that public health measures and possible changes in individual behaviors effectively reduced transmission, especially in hospitals. The temporal patterns of reproduction numbers were similar for healthcare workers and the general population, indicating that on average, an infectious healthcare worker did not infect more people than any other infectious person. We provide a general method to estimate time dependence of parameters in structured epidemic models, which enables investigation of the impact of control measures and behavioral changes in different settings.",2009 Aug 21,"['Cori, Anne', 'Boëlle, Pierre-Yves', 'Thomas, Guy', 'Leung, Gabriel M.', 'Valleron, Alain-Jacques']",PLoS Comput Biol,,,True
25f4a5990fcb174f80bc472629eb47be50d5b3f7,PMC,"Distribution and seasonality of rhinovirus and other respiratory viruses in a cross-section of asthmatic children in Trinidad, West Indies",http://dx.doi.org/10.1186/1824-7288-35-16,PMC2717562,19555507,CC BY,"BACKGROUND: Childhood asthma in the Caribbean is advancing in prevalence and morbidity. Though viral respiratory tract infections are reported triggers for exacerbations, information on these infections with asthma is sparse in Caribbean territories. We examined the distribution of respiratory viruses and their association with seasons in acute and stable asthmatic children in Trinidad. METHODS: In a cross-sectional study of 70 wheezing children attending the emergency department for nebulisation and 80 stable control subjects (2 to 16 yr of age) in the asthma clinic, nasal specimens were collected during the dry (n = 38, January to May) and rainy (n = 112, June to December) seasons. A multitarget, sensitive, specific high-throughput Respiratory MultiCode assay tested for respiratory-virus sequences for eight distinct groups: human rhinovirus, respiratory syncytial virus, parainfluenza virus, influenza virus, metapneumovirus, adenovirus, coronavirus, and enterovirus. RESULTS: Wheezing children had a higher [χ(2 )= 5.561, p = 0.018] prevalence of respiratory viruses compared with stabilized asthmatics (34.3% (24) versus (vs.) 17.5% (14)). Acute asthmatics were thrice as likely to be infected with a respiratory virus (OR = 2.5, 95% CI = 1.2 – 5.3). The predominant pathogens detected in acute versus stable asthmatics were the rhinovirus (RV) (n = 18, 25.7% vs. n = 7, 8.8%; p = 0.005), respiratory syncytial virus B (RSV B) (n = 2, 2.9% vs. n = 4, 5.0%), and enterovirus (n = 1, 1.4% vs. n = 2, 2.5%). Strong odds for rhinoviral infection were observed among nebulised children compared with stable asthmatics (p = 0.005, OR = 3.6, 95% CI = 1.4 – 9.3,). RV was prevalent throughout the year (Dry, n = 6, 15.8%; Rainy, n = 19, 17.0%) and without seasonal association [χ(2 )= 0.028, p = 0.867]. However it was the most frequently detected virus [Dry = 6/10, (60.0%); Rainy = 19/28, (67.9%)] in both seasons. CONCLUSION: Emergent wheezing illnesses during childhood can be linked to infection with rhinovirus in Trinidad's tropical environment. Viral-induced exacerbations of asthma are independent of seasons in this tropical climate. Further clinical and virology investigations are recommended on the role of infections with the rhinovirus in Caribbean childhood wheeze.",2009 Jun 25,"['Matthew, Jason', 'Pinto Pereira, Lexley M', 'Pappas, Tressa E', 'Swenson, Cheri A', 'Grindle, Kris A', 'Roberg, Kathy A', 'Lemanske, Robert F', 'Lee, Wai-Ming', 'Gern, James E']",Ital J Pediatr,,,True
c77f37d083293f7461d47471caa670e765270948,PMC,Using LongSAGE to Detect Biomarkers of Cervical Cancer Potentially Amenable to Optical Contrast Agent Labelling,,PMC2717845,19662225,CC BY,"Sixteen longSAGE libraries from four different clinical stages of cervical intraepithelial neoplasia have enabled us to identify novel cell-surface biomarkers indicative of CIN stage. By comparing gene expression profiles of cervical tissue at early and advanced stages of CIN, several genes are identified to be novel genetic markers. We present fifty-six cell-surface gene products differentially expressed during progression of CIN. These cell surface proteins are being examined to establish their capacity for optical contrast agent binding. Contrast agent visualization will allow real-time assessment of the physiological state of the disease process bringing vast benefit to cancer care. The data discussed in this publication have been submitted to NCBIs Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) and are accessible through GEO Series accession number GSE6252.",2007 Dec 11,"['Kneller, Julie M.', 'Ehlen, Thomas', 'Matisic, Jasenka P.', 'Miller, Dianne', 'Van Niekerk, Dirk', 'Lam, Wan L.', 'Marra, Marco', 'Richards-Kortum, Rebecca', 'Follen, Michelle', 'MacAulay, Calum', 'Jones, Steven J. M.']",Biomark Insights,,,True
541e4b9cc19cdef991c78ff39e6ad79c1f5ecb09,PMC,The role of NH(4)Cl and cysteine proteases in Human Papillomavirus type 16 infection,http://dx.doi.org/10.1186/1743-422X-6-109,PMC2718874,19619315,CC BY,"BACKGROUND: The infectious pathway of the non-enveloped Human Papillomavirus Type 16 (HPV16) includes binding to the cell surface, clathrin-mediated endocytosis, and penetration into an endosome. HPV16 infection was shown to decrease in the presence of the lysosomotrophic neutralizing agent ammonium chloride (NH(4)Cl). NH(4)Cl neutralizes acidic endo-lysosome compartments, thus suggesting that pH was responsible for PV capsid conformational changes leading endosome escape. RESULTS: However, our data suggested that NH(4)Cl blocked infection by preventing the movement of PV viral particles from the early endosome to the caveosome as was shown for JC virus [1,2]. We have confirmed that HPV 16 infection requires the trafficking of reporter-virions to the caveosome as is the case for BPV1 [3,4]. In this manuscript we propose that the observed decrease in infection of PV in the presence of NH(4)Cl was due to a loss of movement of reporter-virions to caveosomes. We also demonstrate that cysteine proteases are involved in the infectious process, and that cathepsin B treatment of viral particles was shown to overcome the block of infection observed in the presence of furin inhibition. We confirmed the need for cathepsin B in HPV16 infection using cathepsin B null mouse embryonic fibroblasts. CONCLUSION: We present data that suggest HPV16 infection is in part mediated by cysteine proteases, and that NH(4)Cl blocks the intracellular trafficking of infectious viral particles. To our knowledge this is the first demonstration that cysteine proteases influence the infection of a non-enveloped virus.",2009 Jul 20,"['Dabydeen, Sarah A', 'Meneses, Patricio I']",Virol J,,,True
013602fc7c2a0e0c4fcfb0e50f6b09fd2c2faa34,PMC,The role of NH(4)Cl and cysteine proteases in Human Papillomavirus type 16 infection,http://dx.doi.org/10.1186/1743-422X-6-109,PMC2718874,19619315,CC BY,"BACKGROUND: The infectious pathway of the non-enveloped Human Papillomavirus Type 16 (HPV16) includes binding to the cell surface, clathrin-mediated endocytosis, and penetration into an endosome. HPV16 infection was shown to decrease in the presence of the lysosomotrophic neutralizing agent ammonium chloride (NH(4)Cl). NH(4)Cl neutralizes acidic endo-lysosome compartments, thus suggesting that pH was responsible for PV capsid conformational changes leading endosome escape. RESULTS: However, our data suggested that NH(4)Cl blocked infection by preventing the movement of PV viral particles from the early endosome to the caveosome as was shown for JC virus [1,2]. We have confirmed that HPV 16 infection requires the trafficking of reporter-virions to the caveosome as is the case for BPV1 [3,4]. In this manuscript we propose that the observed decrease in infection of PV in the presence of NH(4)Cl was due to a loss of movement of reporter-virions to caveosomes. We also demonstrate that cysteine proteases are involved in the infectious process, and that cathepsin B treatment of viral particles was shown to overcome the block of infection observed in the presence of furin inhibition. We confirmed the need for cathepsin B in HPV16 infection using cathepsin B null mouse embryonic fibroblasts. CONCLUSION: We present data that suggest HPV16 infection is in part mediated by cysteine proteases, and that NH(4)Cl blocks the intracellular trafficking of infectious viral particles. To our knowledge this is the first demonstration that cysteine proteases influence the infection of a non-enveloped virus.",2009 Jul 20,"['Dabydeen, Sarah A', 'Meneses, Patricio I']",Virol J,,,False
e4fa5f794163e9b5cd12131d334f83a7818e0838,PMC,The role of NH(4)Cl and cysteine proteases in Human Papillomavirus type 16 infection,http://dx.doi.org/10.1186/1743-422X-6-109,PMC2718874,19619315,CC BY,"BACKGROUND: The infectious pathway of the non-enveloped Human Papillomavirus Type 16 (HPV16) includes binding to the cell surface, clathrin-mediated endocytosis, and penetration into an endosome. HPV16 infection was shown to decrease in the presence of the lysosomotrophic neutralizing agent ammonium chloride (NH(4)Cl). NH(4)Cl neutralizes acidic endo-lysosome compartments, thus suggesting that pH was responsible for PV capsid conformational changes leading endosome escape. RESULTS: However, our data suggested that NH(4)Cl blocked infection by preventing the movement of PV viral particles from the early endosome to the caveosome as was shown for JC virus [1,2]. We have confirmed that HPV 16 infection requires the trafficking of reporter-virions to the caveosome as is the case for BPV1 [3,4]. In this manuscript we propose that the observed decrease in infection of PV in the presence of NH(4)Cl was due to a loss of movement of reporter-virions to caveosomes. We also demonstrate that cysteine proteases are involved in the infectious process, and that cathepsin B treatment of viral particles was shown to overcome the block of infection observed in the presence of furin inhibition. We confirmed the need for cathepsin B in HPV16 infection using cathepsin B null mouse embryonic fibroblasts. CONCLUSION: We present data that suggest HPV16 infection is in part mediated by cysteine proteases, and that NH(4)Cl blocks the intracellular trafficking of infectious viral particles. To our knowledge this is the first demonstration that cysteine proteases influence the infection of a non-enveloped virus.",2009 Jul 20,"['Dabydeen, Sarah A', 'Meneses, Patricio I']",Virol J,,,False
a28137c598e91a3214a936363e59a1ee1f0717ef,PMC,The role of NH(4)Cl and cysteine proteases in Human Papillomavirus type 16 infection,http://dx.doi.org/10.1186/1743-422X-6-109,PMC2718874,19619315,CC BY,"BACKGROUND: The infectious pathway of the non-enveloped Human Papillomavirus Type 16 (HPV16) includes binding to the cell surface, clathrin-mediated endocytosis, and penetration into an endosome. HPV16 infection was shown to decrease in the presence of the lysosomotrophic neutralizing agent ammonium chloride (NH(4)Cl). NH(4)Cl neutralizes acidic endo-lysosome compartments, thus suggesting that pH was responsible for PV capsid conformational changes leading endosome escape. RESULTS: However, our data suggested that NH(4)Cl blocked infection by preventing the movement of PV viral particles from the early endosome to the caveosome as was shown for JC virus [1,2]. We have confirmed that HPV 16 infection requires the trafficking of reporter-virions to the caveosome as is the case for BPV1 [3,4]. In this manuscript we propose that the observed decrease in infection of PV in the presence of NH(4)Cl was due to a loss of movement of reporter-virions to caveosomes. We also demonstrate that cysteine proteases are involved in the infectious process, and that cathepsin B treatment of viral particles was shown to overcome the block of infection observed in the presence of furin inhibition. We confirmed the need for cathepsin B in HPV16 infection using cathepsin B null mouse embryonic fibroblasts. CONCLUSION: We present data that suggest HPV16 infection is in part mediated by cysteine proteases, and that NH(4)Cl blocks the intracellular trafficking of infectious viral particles. To our knowledge this is the first demonstration that cysteine proteases influence the infection of a non-enveloped virus.",2009 Jul 20,"['Dabydeen, Sarah A', 'Meneses, Patricio I']",Virol J,,,False
44efcab56950c5fa796c22e0c46f3537adcf9171,PMC,The role of NH(4)Cl and cysteine proteases in Human Papillomavirus type 16 infection,http://dx.doi.org/10.1186/1743-422X-6-109,PMC2718874,19619315,CC BY,"BACKGROUND: The infectious pathway of the non-enveloped Human Papillomavirus Type 16 (HPV16) includes binding to the cell surface, clathrin-mediated endocytosis, and penetration into an endosome. HPV16 infection was shown to decrease in the presence of the lysosomotrophic neutralizing agent ammonium chloride (NH(4)Cl). NH(4)Cl neutralizes acidic endo-lysosome compartments, thus suggesting that pH was responsible for PV capsid conformational changes leading endosome escape. RESULTS: However, our data suggested that NH(4)Cl blocked infection by preventing the movement of PV viral particles from the early endosome to the caveosome as was shown for JC virus [1,2]. We have confirmed that HPV 16 infection requires the trafficking of reporter-virions to the caveosome as is the case for BPV1 [3,4]. In this manuscript we propose that the observed decrease in infection of PV in the presence of NH(4)Cl was due to a loss of movement of reporter-virions to caveosomes. We also demonstrate that cysteine proteases are involved in the infectious process, and that cathepsin B treatment of viral particles was shown to overcome the block of infection observed in the presence of furin inhibition. We confirmed the need for cathepsin B in HPV16 infection using cathepsin B null mouse embryonic fibroblasts. CONCLUSION: We present data that suggest HPV16 infection is in part mediated by cysteine proteases, and that NH(4)Cl blocks the intracellular trafficking of infectious viral particles. To our knowledge this is the first demonstration that cysteine proteases influence the infection of a non-enveloped virus.",2009 Jul 20,"['Dabydeen, Sarah A', 'Meneses, Patricio I']",Virol J,,,False
a0f9f661ac6e00d87e9b40d93ee4a4ae4605139f,PMC,The role of NH(4)Cl and cysteine proteases in Human Papillomavirus type 16 infection,http://dx.doi.org/10.1186/1743-422X-6-109,PMC2718874,19619315,CC BY,"BACKGROUND: The infectious pathway of the non-enveloped Human Papillomavirus Type 16 (HPV16) includes binding to the cell surface, clathrin-mediated endocytosis, and penetration into an endosome. HPV16 infection was shown to decrease in the presence of the lysosomotrophic neutralizing agent ammonium chloride (NH(4)Cl). NH(4)Cl neutralizes acidic endo-lysosome compartments, thus suggesting that pH was responsible for PV capsid conformational changes leading endosome escape. RESULTS: However, our data suggested that NH(4)Cl blocked infection by preventing the movement of PV viral particles from the early endosome to the caveosome as was shown for JC virus [1,2]. We have confirmed that HPV 16 infection requires the trafficking of reporter-virions to the caveosome as is the case for BPV1 [3,4]. In this manuscript we propose that the observed decrease in infection of PV in the presence of NH(4)Cl was due to a loss of movement of reporter-virions to caveosomes. We also demonstrate that cysteine proteases are involved in the infectious process, and that cathepsin B treatment of viral particles was shown to overcome the block of infection observed in the presence of furin inhibition. We confirmed the need for cathepsin B in HPV16 infection using cathepsin B null mouse embryonic fibroblasts. CONCLUSION: We present data that suggest HPV16 infection is in part mediated by cysteine proteases, and that NH(4)Cl blocks the intracellular trafficking of infectious viral particles. To our knowledge this is the first demonstration that cysteine proteases influence the infection of a non-enveloped virus.",2009 Jul 20,"['Dabydeen, Sarah A', 'Meneses, Patricio I']",Virol J,,,False
1a9fdd51745b132ee92107b4e9c68597d3767b7e,PMC,Beyond traditional surveillance: applying syndromic surveillance to developing settings – opportunities and challenges,http://dx.doi.org/10.1186/1471-2458-9-242,PMC2718884,19607669,CC BY,"BACKGROUND: All countries need effective disease surveillance systems for early detection of outbreaks. The revised International Health Regulations [IHR], which entered into force for all 194 World Health Organization member states in 2007, have expanded traditional infectious disease notification to include surveillance for public health events of potential international importance, even if the causative agent is not yet known. However, there are no clearly established guidelines for how countries should conduct this surveillance, which types of emerging disease syndromes should be reported, nor any means for enforcement. DISCUSSION: The commonly established concept of syndromic surveillance in developed regions encompasses the use of pre-diagnostic information in a near real time fashion for further investigation for public health action. Syndromic surveillance is widely used in North America and Europe, and is typically thought of as a highly complex, technology driven automated tool for early detection of outbreaks. Nonetheless, low technology applications of syndromic surveillance are being used worldwide to augment traditional surveillance. SUMMARY: In this paper, we review examples of these novel applications in the detection of vector-borne diseases, foodborne illness, and sexually transmitted infections. We hope to demonstrate that syndromic surveillance in its basic version is a feasible and effective tool for surveillance in developing countries and may facilitate compliance with the new IHR guidelines.",2009 Jul 16,"['May, Larissa', 'Chretien, Jean-Paul', 'Pavlin, Julie A']",BMC Public Health,,,True
f9a61ae749c3d53492b38119c9fbe5f0e448b52a,PMC,What infection control measures will people carry out to reduce transmission of pandemic influenza? A focus group study,http://dx.doi.org/10.1186/1471-2458-9-258,PMC2720966,19627568,CC BY,"BACKGROUND: Pandemic influenza poses a future health threat against which infection control behaviours may be an important defence. However, there is little qualitative research examining perceptions of infection control measures in the context of pandemic influenza. METHODS: Eight focus groups and one interview were conducted with a purposive sample of 31 participants. Participants were invited to discuss their perceptions of infection transmission and likely adherence to infection control measures in both non-pandemic and pandemic contexts. Infection control measures discussed included handwashing, social distancing and cough hygiene (e.g. covering mouth, disposing of tissues immediately etc.). RESULTS: Thematic analysis revealed that although participants were knowledgeable about infection transmission, most expressed unfavourable attitudes toward control behaviours in non-pandemic situations. However, with the provision of adequate education about control measures and appropriate practical support (e.g. memory aids, access to facilities), most individuals report that they are likely to adhere to infection control protocols in the event of a pandemic. Of the behaviours likely to influence infection transmission, handwashing was regarded by our participants as more feasible than cough and sneeze hygiene and more acceptable than social distancing. CONCLUSION: Handwashing could prove a useful target for health promotion, but interventions to promote infection control may need to address a number of factors identified within this study as potential barriers to carrying out infection control behaviours.",2009 Jul 23,"['Morrison, Leanne G', 'Yardley, Lucy']",BMC Public Health,,,True
e1c0a2349d7445ba4cfd01185dbff3b8346afe45,PMC,What infection control measures will people carry out to reduce transmission of pandemic influenza? A focus group study,http://dx.doi.org/10.1186/1471-2458-9-258,PMC2720966,19627568,CC BY,"BACKGROUND: Pandemic influenza poses a future health threat against which infection control behaviours may be an important defence. However, there is little qualitative research examining perceptions of infection control measures in the context of pandemic influenza. METHODS: Eight focus groups and one interview were conducted with a purposive sample of 31 participants. Participants were invited to discuss their perceptions of infection transmission and likely adherence to infection control measures in both non-pandemic and pandemic contexts. Infection control measures discussed included handwashing, social distancing and cough hygiene (e.g. covering mouth, disposing of tissues immediately etc.). RESULTS: Thematic analysis revealed that although participants were knowledgeable about infection transmission, most expressed unfavourable attitudes toward control behaviours in non-pandemic situations. However, with the provision of adequate education about control measures and appropriate practical support (e.g. memory aids, access to facilities), most individuals report that they are likely to adhere to infection control protocols in the event of a pandemic. Of the behaviours likely to influence infection transmission, handwashing was regarded by our participants as more feasible than cough and sneeze hygiene and more acceptable than social distancing. CONCLUSION: Handwashing could prove a useful target for health promotion, but interventions to promote infection control may need to address a number of factors identified within this study as potential barriers to carrying out infection control behaviours.",2009 Jul 23,"['Morrison, Leanne G', 'Yardley, Lucy']",BMC Public Health,,,False
271eaab0cdf64e3274bd45a4264eeac8f2d1b0d1,PMC,Radiotherapy for oncologic emergencies on weekends: examining reasons for treatment and patterns of practice at a Canadian cancer centre,,PMC2722059,19672425,CC BY,"PURPOSE: Radiotherapy for oncologic emergencies is an important aspect of the management of cancer patients. These emergencies—which include malignant spinal cord compression, brain metastases, superior vena cava obstruction, and uncontrolled tumour hemorrhage —may require treatment outside of hospital hours, particularly on weekends and hospital holidays. To date, there remains no consensus among radiation oncologists regarding the indications and appropriateness of radiotherapy treatment on weekends, and treatment decisions remain largely subjective. The main aim of the present study was to document the incidence and indications for patients receiving emergency treatment on weekends or scheduled hospital holidays at a single institution. The secondary aim was to investigate the compliance of such treatment with the institution’s quality assurance policies, both local and provincial. METHODS: From September 1, 2002, to September 30, 2004, patients being treated over weekends (defined as commencing at 6 pm on a Friday and concluding at 8 am of the next scheduled workday) and hospital holidays were retrospectively identified using the Oncology Patient Information System scheduling module. Relevant patient data—including patient age, sex, primary cancer site, specific radiation field, rationale for treatment, referring hospital, total treatment dose, radiation dose fractionation, inpatient or outpatient status, and duration of treatment—were collected and subsequently analyzed. Comparison to local policy was performed subjectively. RESULTS: Over the 2-year period, 161 patients were prescribed urgent radiotherapy over a weekend or on a hospital holiday. Of this cohort, 68% were treated on both Saturday and Sunday, 22% on Saturday alone, and 10% on Sunday alone. Most patients presented with lung (31%), prostate (18%), and breast cancer (17%). The top reasons for referral for emergency weekend treatment included spinal cord compression (56%), brain metastases (15%), and superior vena cava obstruction (6%). Most of the indications for treatment generally followed the quality assurance policies implemented both locally and provincially. CONCLUSIONS: Patients treated over a weekend or on a hospital holiday were generally found to be treated with appropriate intent. Most treatment indications within this study both complied with provincial policy and showed a pattern of care similar to that seen in other studies in the literature. Local policy appears to be robust; however, policy improvements may allow for more cohesiveness across radiation oncologists in patterns of care in this important group of patients. Comparisons with practice at other institutions would be valuable and also a key step in developing sound guidelines for all members of the radiotherapy community to follow.",2009 Aug,"['Mitera, G.', 'Swaminath, A.', 'Wong, S.', 'Goh, P.', 'Robson, S.', 'Sinclair, E.', 'Danjoux, C.', 'Chow, E.']",Curr Oncol,,,True
9ebef419c2970287a5fd24ea38695453e0bbfffa,PMC,Retrospective analysis of nosocomial infections in the intensive care unit of a tertiary hospital in China during 2003 and 2007,http://dx.doi.org/10.1186/1471-2334-9-115,PMC2722662,19630992,CC BY,"BACKGROUND: Nosocomial infections are a major threat to patients in the intensive care unit (ICU). Limited data exist on the epidemiology of ICU-acquired infections in China. This retrospective study was carried out to determine the current status of nosocomial infection in China. METHODS: A retrospective review of nococomial infections in the ICU of a tertiary hospital in East China between 2003 and 2007 was performed. Nosocomial infections were defined according to the definitions of Centers for Disease Control and Prevention. The overall patient nosocomial infection rate, the incidence density rate of nosocomial infections, the excess length of stay, and distribution of nosocomial infection sites were determined. Then, pathogen and antimicrobial susceptibility profiles were further investigated. RESULTS: Among 1980 patients admitted over the period of time, the overall patient nosocomial infection rate was 26.8% or 51.0 per 1000 patient days., Lower respiratory tract infections (LRTI) accounted for most of the infections (68.4%), followed by urinary tract infections (UTI, 15.9%), bloodstream (BSI, 5.9%), and gastrointestinal tract (GI, 2.5%) infections. There was no significant change in LRTI, UTI and BSI infection rates during the 5 years. However, GI rate was significantly decreased from 5.5% in 2003 to 0.4% in 2007. In addition, A. baumannii, C. albicans and S. epidermidis were the most frequent pathogens isolated in patients with LRTIs, UTIs and BSIs, respectively. The rates of isolates resistant to commonly used antibiotics ranged from 24.0% to 93.1%. CONCLUSION: There was a high and relatively stable rate of nosocomial infections in the ICU of a tertiary hospital in China through year 2003–2007, with some differences in the distribution of the infection sites, and pathogen and antibiotic susceptibility profiles from those reported from the Western countries. Guidelines for surveillance and prevention of nosocomial infections must be implemented in order to reduce the rate.",2009 Jul 25,"['Ding, Ji-Guang', 'Sun, Qing-Feng', 'Li, Ke-Cheng', 'Zheng, Ming-Hua', 'Miao, Xiao-Hui', 'Ni, Wu', 'Hong, Liang', 'Yang, Jin-Xian', 'Ruan, Zhan-Wei', 'Zhou, Rui-Wei', 'Zhou, Hai-Jiao', 'He, Wen-Fei']",BMC Infect Dis,,,True
f3a5b128f4800dbbb0f49ee409acb2c0216e24dc,PMC,Estimating Sensitivity of Laboratory Testing for Influenza in Canada through Modelling,http://dx.doi.org/10.1371/journal.pone.0006681,PMC2722738,19688094,CC BY,"BACKGROUND: The weekly proportion of laboratory tests that are positive for influenza is used in public health surveillance systems to identify periods of influenza activity. We aimed to estimate the sensitivity of influenza testing in Canada based on results of a national respiratory virus surveillance system. METHODS AND FINDINGS: The weekly number of influenza-negative tests from 1999 to 2006 was modelled as a function of laboratory-confirmed positive tests for influenza, respiratory syncytial virus (RSV), adenovirus and parainfluenza viruses, seasonality, and trend using Poisson regression. Sensitivity was calculated as the number of influenza positive tests divided by the number of influenza positive tests plus the model-estimated number of false negative tests. The sensitivity of influenza testing was estimated to be 33% (95%CI 32–34%), varying from 30–40% depending on the season and region. CONCLUSIONS: The estimated sensitivity of influenza tests reported to this national laboratory surveillance system is considerably less than reported test characteristics for most laboratory tests. A number of factors may explain this difference, including sample quality and specimen procurement issues as well as test characteristics. Improved diagnosis would permit better estimation of the burden of influenza.",2009 Aug 18,"['Schanzer, Dena L.', 'Garner, Michael J.', 'Hatchette, Todd F.', 'Langley, Joanne M.', 'Aziz, Samina', 'Tam, Theresa W. S.']",PLoS One,,,True
8987e37e0598cf67e121bc72d1b95b8f1d9fde73,PMC,Rooting human parechovirus evolution in time,http://dx.doi.org/10.1186/1471-2148-9-164,PMC2723090,19604368,CC BY,"BACKGROUND: The Picornaviridae family contains a number of important pathogenic viruses, among which the recently reclassified human parechoviruses (HPeVs). These viruses are widespread and can be grouped in several types. Understanding the evolutionary history of HPeV could answer questions such as how long the circulating lineages last shared a common ancestor and how the evolution of this viral species is shaped by its population dynamics. Using both strict and relaxed clock Bayesian phylogenetics we investigated 1) the substitutions rates of the structural P1 and capsid VP1 regions and 2) evolutionary timescale of currently circulating HPeV lineages. RESULTS: Our estimates reveal that human parechoviruses exhibit high substitution rates for both structural P1 and capsid VP1 regions, respectively 2.21 × 10(-3 )(0.48 – 4.21 × 10(-3)) and 2.79 × 10(-3 )(2.05 – 3.66 × 10(-3)) substitutions per site per year. These are within the range estimated for other picornaviruses. By employing a constant population size coalescent prior, the date of the most recent common ancestor was estimated to be at around 1600 (1427–1733). In addition, by looking at the frequency of synonymous and non-synonymous substitutions within the VP1 gene we show that purifying selection constitutes the dominating evolutionary force leading to strong amino acid conservation. CONCLUSION: In conclusion, our estimates provide a timescale for the evolution of HPeVs and suggest that genetic diversity of current circulating HPeV types has arisen about 400 years ago.",2009 Jul 15,"['Faria, Nuno R', 'de Vries, Michel', 'van Hemert, Formijn J', 'Benschop, Kimberley', 'van der Hoek, Lia']",BMC Evol Biol,,,True
974dbdc07629400038b879b1f76975edfedc442d,PMC,Rooting human parechovirus evolution in time,http://dx.doi.org/10.1186/1471-2148-9-164,PMC2723090,19604368,CC BY,"BACKGROUND: The Picornaviridae family contains a number of important pathogenic viruses, among which the recently reclassified human parechoviruses (HPeVs). These viruses are widespread and can be grouped in several types. Understanding the evolutionary history of HPeV could answer questions such as how long the circulating lineages last shared a common ancestor and how the evolution of this viral species is shaped by its population dynamics. Using both strict and relaxed clock Bayesian phylogenetics we investigated 1) the substitutions rates of the structural P1 and capsid VP1 regions and 2) evolutionary timescale of currently circulating HPeV lineages. RESULTS: Our estimates reveal that human parechoviruses exhibit high substitution rates for both structural P1 and capsid VP1 regions, respectively 2.21 × 10(-3 )(0.48 – 4.21 × 10(-3)) and 2.79 × 10(-3 )(2.05 – 3.66 × 10(-3)) substitutions per site per year. These are within the range estimated for other picornaviruses. By employing a constant population size coalescent prior, the date of the most recent common ancestor was estimated to be at around 1600 (1427–1733). In addition, by looking at the frequency of synonymous and non-synonymous substitutions within the VP1 gene we show that purifying selection constitutes the dominating evolutionary force leading to strong amino acid conservation. CONCLUSION: In conclusion, our estimates provide a timescale for the evolution of HPeVs and suggest that genetic diversity of current circulating HPeV types has arisen about 400 years ago.",2009 Jul 15,"['Faria, Nuno R', 'de Vries, Michel', 'van Hemert, Formijn J', 'Benschop, Kimberley', 'van der Hoek, Lia']",BMC Evol Biol,,,False
ff4fffe02138b0b232334d997965d11fd936916b,PMC,RNA viruses in community-acquired childhood pneumonia in semi-urban Nepal; a cross-sectional study,http://dx.doi.org/10.1186/1741-7015-7-35,PMC2727531,19635124,CC BY,"BACKGROUND: Pneumonia is among the main causes of illness and death in children <5 years of age. There is a need to better describe the epidemiology of viral community-acquired pneumonia (CAP) in developing countries. METHODS: From July 2004 to June 2007, we examined nasopharyngeal aspirates (NPA) from 2,230 cases of pneumonia (World Health Organization criteria) in children 2 to 35 months old recruited in a randomized trial of zinc supplementation at a field clinic in Bhaktapur, Nepal. The specimens were examined for respiratory syncytial virus (RSV), influenza virus type A (InfA) and B (InfB), parainfluenza virus types 1, 2 and 3 (PIV1, PIV2, and PIV3), and human metapneumovirus (hMPV) using a multiplex reverse transcriptase polymerase chain reaction (PCR) assay. RESULTS: We identified 919 virus isolates in 887 (40.0%) of the 2,219 NPA specimens with a valid PCR result, of which 334 (15.1%) yielded RSV, 164 (7.4%) InfA, 129 (5.8%) PIV3, 98 (4.4%) PIV1, 93 (4.2%) hMPV, 84 (3.8%) InfB, and 17 (0.8%) PIV2. CAP occurred in an epidemic pattern with substantial temporal variation during the three years of study. The largest peaks of pneumonia occurrence coincided with peaks of RSV infection, which occurred in epidemics during the rainy season and in winter. The monthly number of RSV infections was positively correlated with relative humidity (r(s )= 0.40, P = 0.01), but not with temperature or rainfall. An hMPV epidemic occurred during one of the three winter seasons and the monthly number of hMPV cases was also associated with relative humidity (r(s )= 0.55, P = 0.0005). CONCLUSION: Respiratory RNA viruses were detected from NPA in 40% of CAP cases in our study. The most commonly isolated viruses were RSV, InfA, and PIV3. RSV infections contributed substantially to the observed CAP epidemics. The occurrence of viral CAP in this community seemed to reflect more or less overlapping micro-epidemics with several respiratory viruses, highlighting the challenges of developing and implementing effective public health control measures.",2009 Jul 27,"['Mathisen, Maria', 'Strand, Tor A', 'Sharma, Biswa N', 'Chandyo, Ram K', 'Valentiner-Branth, Palle', 'Basnet, Sudha', 'Adhikari, Ramesh K', 'Hvidsten, Dag', 'Shrestha, Prakash S', 'Sommerfelt, Halvor']",BMC Med,,,True
0953fa36903063f60627e07f7b4e07f0aec3c4d3,PMC,Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo,http://dx.doi.org/10.1186/1471-2164-10-350,PMC2728740,19650917,CC BY,"BACKGROUND: The role of type I IFNs in protecting against coronavirus (CoV) infections is not fully understood. While CoVs are poor inducers of type I IFNs in tissue culture, several studies have demonstrated the importance of the type I IFN response in controlling MHV infection in animals. The protective effectors against MHV infection are, however, still unknown. RESULTS: In order to get more insight into the antiviral gene expression induced in the brains of MHV-infected mice, we performed whole-genome expression profiling. Three different mouse strains, differing in their susceptibility to infection with MHV, were used. In BALB/c mice, which display high viral loads but are able to control the infection, 57 and 121 genes were significantly differentially expressed (≥ 1.5 fold change) upon infection at 2 and 5 days post infection, respectively. Functional association network analyses demonstrated a strong type I IFN response, with Irf1 and Irf7 as the central players. At 5 days post infection, a type II IFN response also becomes apparent. Both the type I and II IFN response, which were more pronounced in mice with a higher viral load, were not observed in 129SvEv mice, which are much less susceptible to infection with MHV. 129SvEv mice lacking the type I interferon receptor (IFNAR-/-), however, were not able to control the infection. Gene expression profiling of these mice identified type I IFN-independent responses to infection, with IFN-γ as the central player. As the BALB/c and the IFNAR-/- 129SvEv mice demonstrated very similar viral loads in their brains, we also compared their gene expression profiles upon infection with MHV in order to identify type I IFN-dependent transcriptional responses. Many known IFN-inducible genes were detected, several of which have previously been shown to play an important protective role against virus infections. We speculate that the additional type I IFN-dependent genes that we discovered may also be important for protection against MHV infection. CONCLUSION: Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. Profiling of IFNAR-/- mice allowed us to identify type I IFN-independent and -dependent responses. Overall, this study broadens our present knowledge of the type I and II IFN-mediated effector responses during CoV infection in vivo.",2009 Aug 3,"['Raaben, Matthijs', 'Groot Koerkamp, Marian   JA', 'Rottier, Peter JM', 'de Haan, Cornelis AM']",BMC Genomics,,,True
2850eb77e47a839ceca6b3b5d9ac3c1ed988bcad,PMC,Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo,http://dx.doi.org/10.1186/1471-2164-10-350,PMC2728740,19650917,CC BY,"BACKGROUND: The role of type I IFNs in protecting against coronavirus (CoV) infections is not fully understood. While CoVs are poor inducers of type I IFNs in tissue culture, several studies have demonstrated the importance of the type I IFN response in controlling MHV infection in animals. The protective effectors against MHV infection are, however, still unknown. RESULTS: In order to get more insight into the antiviral gene expression induced in the brains of MHV-infected mice, we performed whole-genome expression profiling. Three different mouse strains, differing in their susceptibility to infection with MHV, were used. In BALB/c mice, which display high viral loads but are able to control the infection, 57 and 121 genes were significantly differentially expressed (≥ 1.5 fold change) upon infection at 2 and 5 days post infection, respectively. Functional association network analyses demonstrated a strong type I IFN response, with Irf1 and Irf7 as the central players. At 5 days post infection, a type II IFN response also becomes apparent. Both the type I and II IFN response, which were more pronounced in mice with a higher viral load, were not observed in 129SvEv mice, which are much less susceptible to infection with MHV. 129SvEv mice lacking the type I interferon receptor (IFNAR-/-), however, were not able to control the infection. Gene expression profiling of these mice identified type I IFN-independent responses to infection, with IFN-γ as the central player. As the BALB/c and the IFNAR-/- 129SvEv mice demonstrated very similar viral loads in their brains, we also compared their gene expression profiles upon infection with MHV in order to identify type I IFN-dependent transcriptional responses. Many known IFN-inducible genes were detected, several of which have previously been shown to play an important protective role against virus infections. We speculate that the additional type I IFN-dependent genes that we discovered may also be important for protection against MHV infection. CONCLUSION: Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. Profiling of IFNAR-/- mice allowed us to identify type I IFN-independent and -dependent responses. Overall, this study broadens our present knowledge of the type I and II IFN-mediated effector responses during CoV infection in vivo.",2009 Aug 3,"['Raaben, Matthijs', 'Groot Koerkamp, Marian   JA', 'Rottier, Peter JM', 'de Haan, Cornelis AM']",BMC Genomics,,,False
46f10cdcf6e3db46ebfcb52f4f5cbae7a46b50f0,PMC,Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo,http://dx.doi.org/10.1186/1471-2164-10-350,PMC2728740,19650917,CC BY,"BACKGROUND: The role of type I IFNs in protecting against coronavirus (CoV) infections is not fully understood. While CoVs are poor inducers of type I IFNs in tissue culture, several studies have demonstrated the importance of the type I IFN response in controlling MHV infection in animals. The protective effectors against MHV infection are, however, still unknown. RESULTS: In order to get more insight into the antiviral gene expression induced in the brains of MHV-infected mice, we performed whole-genome expression profiling. Three different mouse strains, differing in their susceptibility to infection with MHV, were used. In BALB/c mice, which display high viral loads but are able to control the infection, 57 and 121 genes were significantly differentially expressed (≥ 1.5 fold change) upon infection at 2 and 5 days post infection, respectively. Functional association network analyses demonstrated a strong type I IFN response, with Irf1 and Irf7 as the central players. At 5 days post infection, a type II IFN response also becomes apparent. Both the type I and II IFN response, which were more pronounced in mice with a higher viral load, were not observed in 129SvEv mice, which are much less susceptible to infection with MHV. 129SvEv mice lacking the type I interferon receptor (IFNAR-/-), however, were not able to control the infection. Gene expression profiling of these mice identified type I IFN-independent responses to infection, with IFN-γ as the central player. As the BALB/c and the IFNAR-/- 129SvEv mice demonstrated very similar viral loads in their brains, we also compared their gene expression profiles upon infection with MHV in order to identify type I IFN-dependent transcriptional responses. Many known IFN-inducible genes were detected, several of which have previously been shown to play an important protective role against virus infections. We speculate that the additional type I IFN-dependent genes that we discovered may also be important for protection against MHV infection. CONCLUSION: Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. Profiling of IFNAR-/- mice allowed us to identify type I IFN-independent and -dependent responses. Overall, this study broadens our present knowledge of the type I and II IFN-mediated effector responses during CoV infection in vivo.",2009 Aug 3,"['Raaben, Matthijs', 'Groot Koerkamp, Marian   JA', 'Rottier, Peter JM', 'de Haan, Cornelis AM']",BMC Genomics,,,False
f26570ca165e9c5560e68b3cd897614d70401f80,PMC,Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo,http://dx.doi.org/10.1186/1471-2164-10-350,PMC2728740,19650917,CC BY,"BACKGROUND: The role of type I IFNs in protecting against coronavirus (CoV) infections is not fully understood. While CoVs are poor inducers of type I IFNs in tissue culture, several studies have demonstrated the importance of the type I IFN response in controlling MHV infection in animals. The protective effectors against MHV infection are, however, still unknown. RESULTS: In order to get more insight into the antiviral gene expression induced in the brains of MHV-infected mice, we performed whole-genome expression profiling. Three different mouse strains, differing in their susceptibility to infection with MHV, were used. In BALB/c mice, which display high viral loads but are able to control the infection, 57 and 121 genes were significantly differentially expressed (≥ 1.5 fold change) upon infection at 2 and 5 days post infection, respectively. Functional association network analyses demonstrated a strong type I IFN response, with Irf1 and Irf7 as the central players. At 5 days post infection, a type II IFN response also becomes apparent. Both the type I and II IFN response, which were more pronounced in mice with a higher viral load, were not observed in 129SvEv mice, which are much less susceptible to infection with MHV. 129SvEv mice lacking the type I interferon receptor (IFNAR-/-), however, were not able to control the infection. Gene expression profiling of these mice identified type I IFN-independent responses to infection, with IFN-γ as the central player. As the BALB/c and the IFNAR-/- 129SvEv mice demonstrated very similar viral loads in their brains, we also compared their gene expression profiles upon infection with MHV in order to identify type I IFN-dependent transcriptional responses. Many known IFN-inducible genes were detected, several of which have previously been shown to play an important protective role against virus infections. We speculate that the additional type I IFN-dependent genes that we discovered may also be important for protection against MHV infection. CONCLUSION: Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. Profiling of IFNAR-/- mice allowed us to identify type I IFN-independent and -dependent responses. Overall, this study broadens our present knowledge of the type I and II IFN-mediated effector responses during CoV infection in vivo.",2009 Aug 3,"['Raaben, Matthijs', 'Groot Koerkamp, Marian   JA', 'Rottier, Peter JM', 'de Haan, Cornelis AM']",BMC Genomics,,,False
d9c67ce0ec43104c6b6252fac340320752efd6e7,PMC,Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo,http://dx.doi.org/10.1186/1471-2164-10-350,PMC2728740,19650917,CC BY,"BACKGROUND: The role of type I IFNs in protecting against coronavirus (CoV) infections is not fully understood. While CoVs are poor inducers of type I IFNs in tissue culture, several studies have demonstrated the importance of the type I IFN response in controlling MHV infection in animals. The protective effectors against MHV infection are, however, still unknown. RESULTS: In order to get more insight into the antiviral gene expression induced in the brains of MHV-infected mice, we performed whole-genome expression profiling. Three different mouse strains, differing in their susceptibility to infection with MHV, were used. In BALB/c mice, which display high viral loads but are able to control the infection, 57 and 121 genes were significantly differentially expressed (≥ 1.5 fold change) upon infection at 2 and 5 days post infection, respectively. Functional association network analyses demonstrated a strong type I IFN response, with Irf1 and Irf7 as the central players. At 5 days post infection, a type II IFN response also becomes apparent. Both the type I and II IFN response, which were more pronounced in mice with a higher viral load, were not observed in 129SvEv mice, which are much less susceptible to infection with MHV. 129SvEv mice lacking the type I interferon receptor (IFNAR-/-), however, were not able to control the infection. Gene expression profiling of these mice identified type I IFN-independent responses to infection, with IFN-γ as the central player. As the BALB/c and the IFNAR-/- 129SvEv mice demonstrated very similar viral loads in their brains, we also compared their gene expression profiles upon infection with MHV in order to identify type I IFN-dependent transcriptional responses. Many known IFN-inducible genes were detected, several of which have previously been shown to play an important protective role against virus infections. We speculate that the additional type I IFN-dependent genes that we discovered may also be important for protection against MHV infection. CONCLUSION: Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. Profiling of IFNAR-/- mice allowed us to identify type I IFN-independent and -dependent responses. Overall, this study broadens our present knowledge of the type I and II IFN-mediated effector responses during CoV infection in vivo.",2009 Aug 3,"['Raaben, Matthijs', 'Groot Koerkamp, Marian   JA', 'Rottier, Peter JM', 'de Haan, Cornelis AM']",BMC Genomics,,,False
44729b69ab4b60fc3e863c655d1dcc0bd02db6de,PMC,"Liquorice Health Check, Oro-Dental Implications, and a Case Report",http://dx.doi.org/10.1155/2009/170735,PMC2729489,19707475,CC BY,"Liquorice has an active substance, Glycyrrhizin which inhibits the conversion of precursor cortisol to cortisone by inhibiting the enzyme 11-betahydroxysteroid dehydrogenase. When imbibed, liquorice acts like hyperaldosteronism which presents with typical symptoms including high blood pressure, low blood potassium, and muscle pain and weakness. This article appraises physiological and pharmacological effects on health of liquorice, critiques products containing liquorice, describes a typical case report of liquorice-induced hypertension, and appraises oral effects from consumption of liquorice products.",2009 Jul 8,"Touyz, Louis Z. G.",Case Rep Med,,,True
a2759c88de238c2a28c8084c108538c8985104a4,PMC,'ONE HEALTH' and parasitology,http://dx.doi.org/10.1186/1756-3305-2-36,PMC2729733,19674442,CC BY,,2009 Aug 12,"['Kaplan, Bruce', 'Kahn, Laura H', 'Monath, Thomas P', 'Woodall, Jack']",Parasit Vectors,,,True
4424d28032612c98a50bf8654f61badc6cd22c55,PMC,Early Epidemiological Assessment of the Virulence of Emerging Infectious Diseases: A Case Study of an Influenza Pandemic,http://dx.doi.org/10.1371/journal.pone.0006852,PMC2729920,19718434,CC BY,"BACKGROUND: The case fatality ratio (CFR), the ratio of deaths from an infectious disease to the number of cases, provides an assessment of virulence. Calculation of the ratio of the cumulative number of deaths to cases during the course of an epidemic tends to result in a biased CFR. The present study develops a simple method to obtain an unbiased estimate of confirmed CFR (cCFR), using only the confirmed cases as the denominator, at an early stage of epidemic, even when there have been only a few deaths. METHODOLOGY/PRINCIPAL FINDINGS: Our method adjusts the biased cCFR by a factor of underestimation which is informed by the time from symptom onset to death. We first examine the approach by analyzing an outbreak of severe acute respiratory syndrome in Hong Kong (2003) with known unbiased cCFR estimate, and then investigate published epidemiological datasets of novel swine-origin influenza A (H1N1) virus infection in the USA and Canada (2009). Because observation of a few deaths alone does not permit estimating the distribution of the time from onset to death, the uncertainty is addressed by means of sensitivity analysis. The maximum likelihood estimate of the unbiased cCFR for influenza may lie in the range of 0.16–4.48% within the assumed parameter space for a factor of underestimation. The estimates for influenza suggest that the virulence is comparable to the early estimate in Mexico. Even when there have been no deaths, our model permits estimating a conservative upper bound of the cCFR. CONCLUSIONS: Although one has to keep in mind that the cCFR for an entire population is vulnerable to its variations among sub-populations and underdiagnosis, our method is useful for assessing virulence at the early stage of an epidemic and for informing policy makers and the public.",2009 Aug 31,"['Nishiura, Hiroshi', 'Klinkenberg, Don', 'Roberts, Mick', 'Heesterbeek, Johan A. P.']",PLoS One,,,True
3aeb264d986c987ced699cb2c711eb022b697d5a,PMC,Empirical Relationship between Intra-Purine and Intra-Pyrimidine Differences in Conserved Gene Sequences,http://dx.doi.org/10.1371/journal.pone.0006829,PMC2730015,19714250,CC BY,"DNA sequences seen in the normal character-based representation appear to have a formidable mixing of the four nucleotides without any apparent order. Nucleotide frequencies and distributions in the sequences have been studied extensively, since the simple rule given by Chargaff almost a century ago that equates the total number of purines to the pyrimidines in a duplex DNA sequence. While it is difficult to trace any relationship between the bases from studies in the character representation of a DNA sequence, graphical representations may provide a clue. These novel representations of DNA sequences have been useful in providing an overview of base distribution and composition of the sequences and providing insights into many hidden structures. We report here our observation based on a graphical representation that the intra-purine and intra-pyrimidine differences in sequences of conserved genes generally follow a quadratic distribution relationship and show that this may have arisen from mutations in the sequences over evolutionary time scales. From this hitherto undescribed relationship for the gene sequences considered in this report we hypothesize that such relationships may be characteristic of these sequences and therefore could become a barrier to large scale sequence alterations that override such characteristics, perhaps through some monitoring process inbuilt in the DNA sequences. Such relationship also raises the possibility of intron sequences playing an important role in maintaining the characteristics and could be indicative of possible intron-late phenomena.",2009 Aug 28,"Nandy, Ashesh",PLoS One,,,True
41b92c19649c6e5cd6a4e883e7edf9a43589bcdd,PMC,Identification of protein functions using a machine-learning approach based on sequence-derived properties,http://dx.doi.org/10.1186/1477-5956-7-27,PMC2731080,19664241,CC BY,"BACKGROUND: Predicting the function of an unknown protein is an essential goal in bioinformatics. Sequence similarity-based approaches are widely used for function prediction; however, they are often inadequate in the absence of similar sequences or when the sequence similarity among known protein sequences is statistically weak. This study aimed to develop an accurate prediction method for identifying protein function, irrespective of sequence and structural similarities. RESULTS: A highly accurate prediction method capable of identifying protein function, based solely on protein sequence properties, is described. This method analyses and identifies specific features of the protein sequence that are highly correlated with certain protein functions and determines the combination of protein sequence features that best characterises protein function. Thirty-three features that represent subtle differences in local regions and full regions of the protein sequences were introduced. On the basis of 484 features extracted solely from the protein sequence, models were built to predict the functions of 11 different proteins from a broad range of cellular components, molecular functions, and biological processes. The accuracy of protein function prediction using random forests with feature selection ranged from 94.23% to 100%. The local sequence information was found to have a broad range of applicability in predicting protein function. CONCLUSION: We present an accurate prediction method using a machine-learning approach based solely on protein sequence properties. The primary contribution of this paper is to propose new PNPRD features representing global and/or local differences in sequences, based on positively and/or negatively charged residues, to assist in predicting protein function. In addition, we identified a compact and useful feature subset for predicting the function of various proteins. Our results indicate that sequence-based classifiers can provide good results among a broad range of proteins, that the proposed features are useful in predicting several functions, and that the combination of our and traditional features may support the creation of a discriminative feature set for specific protein functions.",2009 Aug 9,"['Lee, Bum Ju', 'Shin, Moon Sun', 'Oh, Young Joon', 'Oh, Hae Seok', 'Ryu, Keun Ho']",Proteome Sci,,,True
d0a8b7f4cb8c1c634db8716057ae04282f65687f,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,True
e5a9130fe91644dc7bd9ef4f8d26e1d07faaca08,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,True
1a009c62e2e9971384488abc4711a6be0ef2b7c2,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
d3909545537c084455f830501a1c963e86ea7d4a,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
1d96351438bef1bb2201e1df8b0825cadde42d18,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
a15c6c90166e58a98c9d77cbc91709e106287822,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
cb96cf78ed9921212f87428bd2fe645f5f8f297e,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
bb67ff9a080a6fa65beec9c32112a630a751cf22,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
e7bc5cd2fa92efa6d0cf8b86fcc091ecf6871d6e,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
e887d0bb480276ab8336f933cf2b4fa386f40a83,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
335e0b9c181449a0f69d1d30b735ec16634c56e8,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
eb2b8dfa100caf17efae9694e4d79b529c08d625,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
af756126a149f2b19d5aeaa1c43342a1c1925722,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
10ccc558b53162f044ff17644fe0aff4871004f0,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
d23e47433d01c5edfcb3b2a3b7fd2d4be86e8486,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
64d2865dc52601e41e19d7750e1caf7f1882e4f0,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
d99d0f3c265c5bb1df189303705a530165efad3b,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
41b565d9cc80b5722f2a956316337a78156bcfe6,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
a7996cf11400a57648b6220050af479e409e90d4,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
5fbef12339e19adcc9061cf8fe0dbedb4c88f01d,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
cea8ca13bca61f7708da98cb4550976fb6a8c1b5,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
1839b151394acdff904f028d3b72ca7c055f3dd1,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
cb053f909b2187a64b73a5e7ec073801ebed4a29,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
48b442add80b6679538a8394240b016324dd8744,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
2fc6a88c3419a5ab1df09b24a094fe33e096facb,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
f169b544b6a8b585490f106910624bb1935f7afd,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
f5dd0ff704b7ebae917bb175835471471b3947e1,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
faced14dbb3af799525a67f97bd6d5b904a365e3,PMC,The Application of Genomics to Emerging Zoonotic Viral Diseases,http://dx.doi.org/10.1371/journal.ppat.1000557,PMC2734983,19855817,CC BY,"Interspecies transmission of pathogens may result in the emergence of new infectious diseases in humans as well as in domestic and wild animals. Genomics tools such as high-throughput sequencing, mRNA expression profiling, and microarray-based analysis of single nucleotide polymorphisms are providing unprecedented ways to analyze the diversity of the genomes of emerging pathogens as well as the molecular basis of the host response to them. By comparing and contrasting the outcomes of an emerging infection with those of closely related pathogens in different but related host species, we can further delineate the various host pathways determining the outcome of zoonotic transmission and adaptation to the newly invaded species. The ultimate challenge is to link pathogen and host genomics data with biological outcomes of zoonotic transmission and to translate the integrated data into novel intervention strategies that eventually will allow the effective control of newly emerging infectious diseases.",2009 Oct 26,"['Haagmans, Bart L.', 'Andeweg, Arno C.', 'Osterhaus, Albert D. M. E.']",PLoS Pathog,,,True
fe2000f280297c40bc53ce95d703a9ca6aac19fd,PMC,Differential Regulation of Type I Interferon and Epidermal Growth Factor Pathways by a Human Respirovirus Virulence Factor,http://dx.doi.org/10.1371/journal.ppat.1000587,PMC2736567,19806178,CC BY,"A number of paramyxoviruses are responsible for acute respiratory infections in children, elderly and immuno-compromised individuals, resulting in airway inflammation and exacerbation of chronic diseases like asthma. To understand the molecular pathogenesis of these infections, we searched for cellular targets of the virulence protein C of human parainfluenza virus type 3 (hPIV3-C). We found that hPIV3-C interacts directly through its C-terminal domain with STAT1 and GRB2, whereas C proteins from measles or Nipah viruses failed to do so. Binding to STAT1 explains the previously reported capacity of hPIV3-C to block type I interferon signaling, but the interaction with GRB2 was unexpected. This adaptor protein bridges Epidermal Growth Factor (EGF) receptor to MAPK/ERK pathway, a signaling cascade recently found to be involved in airway inflammatory response. We report that either hPIV3 infection or transient expression of hPIV3-C both increase cellular response to EGF, as assessed by Elk1 transactivation and phosphorylation levels of ERK1/2, 40S ribosomal subunit protein S6 and translation initiation factor 4E (eIF4E). Furthermore, inhibition of MAPK/ERK pathway with U0126 prevented viral protein expression in infected cells. Altogether, our data provide molecular basis to explain the role of hPIV3-C as a virulence factor and determinant of pathogenesis and demonstrate that Paramyxoviridae have evolved a single virulence factor to block type I interferon signaling and to boost simultaneous cellular response to growth factors.",2009 Sep 18,"['Caignard, Grégory', 'Komarova, Anastassia V.', 'Bouraï, Mehdi', 'Mourez, Thomas', 'Jacob, Yves', 'Jones, Louis M.', 'Rozenberg, Flore', 'Vabret, Astrid', 'Freymuth, François', 'Tangy, Frédéric', 'Vidalain, Pierre-Olivier']",PLoS Pathog,,,True
4d7ed140eb8fb2b02900f7ed3ad33e99dc438989,PMC,Identification and validation of suitable endogenous reference genes for gene expression studies in human peripheral blood,http://dx.doi.org/10.1186/1755-8794-2-49,PMC2736983,19656400,CC BY,"BACKGROUND: Gene expression studies require appropriate normalization methods. One such method uses stably expressed reference genes. Since suitable reference genes appear to be unique for each tissue, we have identified an optimal set of the most stably expressed genes in human blood that can be used for normalization. METHODS: Whole-genome Affymetrix Human 2.0 Plus arrays were examined from 526 samples of males and females ages 2 to 78, including control subjects and patients with Tourette syndrome, stroke, migraine, muscular dystrophy, and autism. The top 100 most stably expressed genes with a broad range of expression levels were identified. To validate the best candidate genes, we performed quantitative RT-PCR on a subset of 10 genes (TRAP1, DECR1, FPGS, FARP1, MAPRE2, PEX16, GINS2, CRY2, CSNK1G2 and A4GALT), 4 commonly employed reference genes (GAPDH, ACTB, B2M and HMBS) and PPIB, previously reported to be stably expressed in blood. Expression stability and ranking analysis were performed using GeNorm and NormFinder algorithms. RESULTS: Reference genes were ranked based on their expression stability and the minimum number of genes needed for nomalization as calculated using GeNorm showed that the fewest, most stably expressed genes needed for acurate normalization in RNA expression studies of human whole blood is a combination of TRAP1, FPGS, DECR1 and PPIB. We confirmed the ranking of the best candidate control genes by using an alternative algorithm (NormFinder). CONCLUSION: The reference genes identified in this study are stably expressed in whole blood of humans of both genders with multiple disease conditions and ages 2 to 78. Importantly, they also have different functions within cells and thus should be expressed independently of each other. These genes should be useful as normalization genes for microarray and RT-PCR whole blood studies of human physiology, metabolism and disease.",2009 Aug 5,"['Stamova, Boryana S', 'Apperson, Michelle', 'Walker, Wynn L', 'Tian, Yingfang', 'Xu, Huichun', 'Adamczy, Peter', 'Zhan, Xinhua', 'Liu, Da-Zhi', 'Ander, Bradley P', 'Liao, Isaac H', 'Gregg, Jeffrey P', 'Turner, Renee J', 'Jickling, Glen', 'Lit, Lisa', 'Sharp, Frank R']",BMC Med Genomics,,,True
335b0a3f21f764adcbe20ff71e422d823c410098,PMC,A Serological Survey of Infectious Disease in Yellowstone National Park’s Canid Community,http://dx.doi.org/10.1371/journal.pone.0007042,PMC2738425,19756151,CC0,"BACKGROUND: Gray wolves (Canis lupus) were reintroduced into Yellowstone National Park (YNP) after a >70 year absence, and as part of recovery efforts, the population has been closely monitored. In 1999 and 2005, pup survival was significantly reduced, suggestive of disease outbreaks. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed sympatric wolf, coyote (Canis latrans), and red fox (Vulpes vulpes) serologic data from YNP, spanning 1991–2007, to identify long-term patterns of pathogen exposure, identify associated risk factors, and examine evidence for disease-induced mortality among wolves for which there were survival data. We found high, constant exposure to canine parvovirus (wolf seroprevalence: 100%; coyote: 94%), canine adenovirus-1 (wolf pups [0.5–0.9 yr]: 91%, adults [≥1 yr]: 96%; coyote juveniles [0.5–1.5 yrs]: 18%, adults [≥1.6 yrs]: 83%), and canine herpesvirus (wolf: 87%; coyote juveniles: 23%, young adults [1.6–4.9 yrs]: 51%, old adults [≥5 yrs]: 87%) suggesting that these pathogens were enzootic within YNP wolves and coyotes. An average of 50% of wolves exhibited exposure to the protozoan parasite, Neospora caninum, although individuals’ odds of exposure tended to increase with age and was temporally variable. Wolf, coyote, and fox exposure to canine distemper virus (CDV) was temporally variable, with evidence for distinct multi-host outbreaks in 1999 and 2005, and perhaps a smaller, isolated outbreak among wolves in the interior of YNP in 2002. The years of high wolf-pup mortality in 1999 and 2005 in the northern region of the park were correlated with peaks in CDV seroprevalence, suggesting that CDV contributed to the observed mortality. CONCLUSIONS/SIGNIFICANCE: Of the pathogens we examined, none appear to jeopardize the long-term population of canids in YNP. However, CDV appears capable of causing short-term population declines. Additional information on how and where CDV is maintained and the frequency with which future epizootics might be expected might be useful for future management of the Northern Rocky Mountain wolf population.",2009 Sep 16,"['Almberg, Emily S.', 'Mech, L. David', 'Smith, Douglas W.', 'Sheldon, Jennifer W.', 'Crabtree, Robert L.']",PLoS One,,,True
47266ea82145a11ad6e82db70a4d0fbd86a27cb2,PMC,SNAD: sequence name annotation-based designer,http://dx.doi.org/10.1186/1471-2105-10-251,PMC2739203,19682364,CC BY,"BACKGROUND: A growing diversity of biological data is tagged with unique identifiers (UIDs) associated with polynucleotides and proteins to ensure efficient computer-mediated data storage, maintenance, and processing. These identifiers, which are not informative for most people, are often substituted by biologically meaningful names in various presentations to facilitate utilization and dissemination of sequence-based knowledge. This substitution is commonly done manually that may be a tedious exercise prone to mistakes and omissions. RESULTS: Here we introduce SNAD (Sequence Name Annotation-based Designer) that mediates automatic conversion of sequence UIDs (associated with multiple alignment or phylogenetic tree, or supplied as plain text list) into biologically meaningful names and acronyms. This conversion is directed by precompiled or user-defined templates that exploit wealth of annotation available in cognate entries of external databases. Using examples, we demonstrate how this tool can be used to generate names for practical purposes, particularly in virology. CONCLUSION: A tool for controllable annotation-based conversion of sequence UIDs into biologically meaningful names and acronyms has been developed and placed into service, fostering links between quality of sequence annotation, and efficiency of communication and knowledge dissemination among researchers.",2009 Aug 14,"['Sidorov, Igor A', 'Reshetov, Denis A', 'Gorbalenya, Alexander E']",BMC Bioinformatics,,,True
79316a90d0cd339b0d8d40407555b253994fd833,PMC,Gene Expression Profiling in Cells with Enhanced γ-Secretase Activity,http://dx.doi.org/10.1371/journal.pone.0006952,PMC2739295,19763259,CC BY,"BACKGROUND: Processing by γ-secretase of many type-I membrane protein substrates triggers signaling cascades by releasing intracellular domains (ICDs) that, following nuclear translocation, modulate the transcription of different genes regulating a diverse array of cellular and biological processes. Because the list of γ-secretase substrates is growing quickly and this enzyme is a cancer and Alzheimer's disease therapeutic target, the mapping of γ-secretase activity susceptible gene transcription is important for sharpening our view of specific affected genes, molecular functions and biological pathways. METHODOLOGY/PRINCIPAL FINDINGS: To identify genes and molecular functions transcriptionally affected by γ-secretase activity, the cellular transcriptomes of Chinese hamster ovary (CHO) cells with enhanced and inhibited γ-secretase activity were analyzed and compared by cDNA microarray. The functional clustering by FatiGO of the 1,981 identified genes revealed over- and under-represented groups with multiple activities and functions. Single genes with the most pronounced transcriptional susceptibility to γ-secretase activity were evaluated by real-time PCR. Among the 21 validated genes, the strikingly decreased transcription of PTPRG and AMN1 and increased transcription of UPP1 potentially support data on cell cycle disturbances relevant to cancer, stem cell and neurodegenerative diseases' research. The mapping of interactions of proteins encoded by the validated genes exclusively relied on evidence-based data and revealed broad effects on Wnt pathway members, including WNT3A and DVL3. Intriguingly, the transcription of TERA, a gene of unknown function, is affected by γ-secretase activity and was significantly altered in the analyzed human Alzheimer's disease brain cortices. CONCLUSIONS/SIGNIFICANCE: Investigating the effects of γ-secretase activity on gene transcription has revealed several affected clusters of molecular functions and, more specifically, 21 genes that hold significant potential for a better understanding of the biology of γ-secretase and its roles in cancer and Alzheimer's disease pathology.",2009 Sep 18,"['Magold, Alexandra I.', 'Cacquevel, Matthias', 'Fraering, Patrick C.']",PLoS One,,,True
963285bb042097a1c7b9053b74db098d24818b25,PMC,Reverse genetic characterization of the natural genomic deletion in SARS-Coronavirus strain Frankfurt-1 open reading frame 7b reveals an attenuating function of the 7b protein in-vitro and in-vivo,http://dx.doi.org/10.1186/1743-422X-6-131,PMC2739521,19698190,CC BY,"During the outbreak of SARS in 2002/3, a prototype virus was isolated from a patient in Frankfurt/Germany (strain Frankfurt-1). As opposed to all other SARS-Coronavirus strains, Frankfurt-1 has a 45-nucleotide deletion in the transmembrane domain of its ORF 7b protein. When over-expressed in HEK 293 cells, the full-length protein but not the variant with the deletion caused interferon beta induction and cleavage of procaspase 3. To study the role of ORF 7b in the context of virus replication, we cloned a full genome cDNA copy of Frankfurt-1 in a bacterial artificial chromosome downstream of a T7 RNA polymerase promoter. Transfection of capped RNA transcribed from this construct yielded infectious virus that was indistinguishable from the original virus isolate. The presumed Frankfurt-1 ancestor with an intact ORF 7b was reconstructed. In CaCo-2 and HUH7 cells, but not in Vero cells, the variant carrying the ORF 7b deletion had a replicative advantage against the parental virus (4- and 6-fold increase of virus RNA in supernatant, respectively). This effect was neither associated with changes in the induction or secretion of type I interferon, nor with altered induction of apoptosis in cell culture. However, pretreatment of cells with interferon beta caused the deleted virus to replicate to higher titers than the parental strain (3.4-fold in Vero cells, 7.9-fold in CaCo-2 cells). In Syrian Golden Hamsters inoculated intranasally with 10e4 plaque forming units of either virus, mean titers of infectious virus and viral RNA in the lungs after 24 h were increased 23- and 94.8-fold, respectively, with the deleted virus. This difference could explain earlier observations of enhanced virulence of Frankfurt-1 in Hamsters as compared to other SARS-Coronavirus reference strains and identifies the SARS-CoV 7b protein as an attenuating factor with the SARS-Coronavirus genome. Because attenuation was focused on the early phase of infection in-vivo, ORF 7b might have contributed to the delayed accumulation of virus in patients that was suggested to have limited the spread of the SARS epidemic.",2009 Aug 24,"['Pfefferle, Susanne', 'Krähling, Verena', 'Ditt, Vanessa', 'Grywna, Klaus', 'Mühlberger, Elke', 'Drosten, Christian']",Virol J,,,True
99e788920d9bc9e4792a54d4daa546045c04f9cc,PMC,Different altered stage correlative expression of high abundance acute-phase proteins in sera of patients with epithelial ovarian carcinoma,http://dx.doi.org/10.1186/1756-8722-2-37,PMC2739531,19709441,CC BY,"BACKGROUND: The general enhanced expression of α(1)-antichymotrypsin (ACT), clusterin (CLU), α(1)-antitrypsin (AAT), haptoglobin β-chain (HAP), and leucine rich glycoprotein (LRG) in the sera of patients with epithelial ovarian carcinoma (EOCa) was recently reported. In the present study, we compared the expression of the serum acute-phase proteins (APPs) in the patients according to their stages of cancer. RESULTS: Different altered stage correlative expression of the high abundance serum APPs was demonstrated in sera of the patients studied. While the expression of ACT, HAP and AAT appeared to demonstrate positive correlation with the three initial stages of the cancer, inverse correlation was apparently detected in the expression of LRG and CLU. For patients who were diagnosed with stage IV of the cancer, expression of the serum APPs did not conform to the altered progression changes. CONCLUSION: Our results highlight the potential prognostic significance of selective high abundance serum APPs in patients with EOCa.",2009 Aug 27,"['Chen, Yeng', 'Lim, Boon-Kiong', 'Hashim, Onn H']",J Hematol Oncol,,,True
f06b500cbbffe7641b716dbbb90f0d40ed7839d6,PMC,Bayesian Phylogeography Finds Its Roots,http://dx.doi.org/10.1371/journal.pcbi.1000520,PMC2740835,19779555,CC BY,"As a key factor in endemic and epidemic dynamics, the geographical distribution of viruses has been frequently interpreted in the light of their genetic histories. Unfortunately, inference of historical dispersal or migration patterns of viruses has mainly been restricted to model-free heuristic approaches that provide little insight into the temporal setting of the spatial dynamics. The introduction of probabilistic models of evolution, however, offers unique opportunities to engage in this statistical endeavor. Here we introduce a Bayesian framework for inference, visualization and hypothesis testing of phylogeographic history. By implementing character mapping in a Bayesian software that samples time-scaled phylogenies, we enable the reconstruction of timed viral dispersal patterns while accommodating phylogenetic uncertainty. Standard Markov model inference is extended with a stochastic search variable selection procedure that identifies the parsimonious descriptions of the diffusion process. In addition, we propose priors that can incorporate geographical sampling distributions or characterize alternative hypotheses about the spatial dynamics. To visualize the spatial and temporal information, we summarize inferences using virtual globe software. We describe how Bayesian phylogeography compares with previous parsimony analysis in the investigation of the influenza A H5N1 origin and H5N1 epidemiological linkage among sampling localities. Analysis of rabies in West African dog populations reveals how virus diffusion may enable endemic maintenance through continuous epidemic cycles. From these analyses, we conclude that our phylogeographic framework will make an important asset in molecular epidemiology that can be easily generalized to infer biogeogeography from genetic data for many organisms.",2009 Sep 25,"['Lemey, Philippe', 'Rambaut, Andrew', 'Drummond, Alexei J.', 'Suchard, Marc A.']",PLoS Comput Biol,,,True
d582ab2a736fc7555df7ad6512afbdcd74056201,PMC,Increased ATP generation in the host cell is required for efficient vaccinia virus production,http://dx.doi.org/10.1186/1423-0127-16-80,PMC2741444,19725950,CC BY,"To search for cellular genes up-regulated by vaccinia virus (VV) infection, differential display-reverse transcription-polymerase chain reaction (ddRT-PCR) assays were used to examine the expression of mRNAs from mock-infected and VV-infected HeLa cells. Two mitochondrial genes for proteins that are part of the electron transport chain that generates ATP, ND4 and CO II, were up-regulated after VV infection. Up-regulation of ND4 level by VV infection was confirmed by Western blotting analysis. Up-regulation of ND4 was reduced by the MAPK inhibitor, apigenin, which has been demonstrated elsewhere to inhibit VV replication. The induction of ND4 expression occurred after viral DNA replication since ara C, an inhibitor of poxviral DNA replication, could block this induction. ATP production was increased in the host cells after VV infection. Moreover, 4.5 μM oligomycin, an inhibitor of ATP production, reduced the ATP level 13 hr after virus infection to that of mock-infected cells and inhibited viral protein expression and virus production, suggesting that increased ATP production is required for efficient VV production. Our results further suggest that induction of ND4 expression is through a Bcl-2 independent pathway.",2009 Sep 2,"['Chang, Chia-Wei', 'Li, Hui-Chun', 'Hsu, Che-Fang', 'Chang, Chiao-Yen', 'Lo, Shih-Yen']",J Biomed Sci,,,True
b7e7ff011d768680bee745105bd24389068a5a1f,PMC,Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways,http://dx.doi.org/10.1371/journal.ppat.1000594,PMC2741593,19763269,CC0,"One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.",2009 Sep 18,"['Rong, Rong', 'Li, Bing', 'Lynch, Rebecca M.', 'Haaland, Richard E.', 'Murphy, Megan K.', 'Mulenga, Joseph', 'Allen, Susan A.', 'Pinter, Abraham', 'Shaw, George M.', 'Hunter, Eric', 'Robinson, James E.', 'Gnanakaran, S.', 'Derdeyn, Cynthia A.']",PLoS Pathog,,,True
fc473cd495077e770af4646766ab52ec5f69ea5c,PMC,Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways,http://dx.doi.org/10.1371/journal.ppat.1000594,PMC2741593,19763269,CC0,"One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.",2009 Sep 18,"['Rong, Rong', 'Li, Bing', 'Lynch, Rebecca M.', 'Haaland, Richard E.', 'Murphy, Megan K.', 'Mulenga, Joseph', 'Allen, Susan A.', 'Pinter, Abraham', 'Shaw, George M.', 'Hunter, Eric', 'Robinson, James E.', 'Gnanakaran, S.', 'Derdeyn, Cynthia A.']",PLoS Pathog,,,False
660a2426bce5b77f9977be2c5149b548523d601b,PMC,Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways,http://dx.doi.org/10.1371/journal.ppat.1000594,PMC2741593,19763269,CC0,"One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.",2009 Sep 18,"['Rong, Rong', 'Li, Bing', 'Lynch, Rebecca M.', 'Haaland, Richard E.', 'Murphy, Megan K.', 'Mulenga, Joseph', 'Allen, Susan A.', 'Pinter, Abraham', 'Shaw, George M.', 'Hunter, Eric', 'Robinson, James E.', 'Gnanakaran, S.', 'Derdeyn, Cynthia A.']",PLoS Pathog,,,False
4204ef31e94508ac502575600aa56747d7674adb,PMC,Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways,http://dx.doi.org/10.1371/journal.ppat.1000594,PMC2741593,19763269,CC0,"One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.",2009 Sep 18,"['Rong, Rong', 'Li, Bing', 'Lynch, Rebecca M.', 'Haaland, Richard E.', 'Murphy, Megan K.', 'Mulenga, Joseph', 'Allen, Susan A.', 'Pinter, Abraham', 'Shaw, George M.', 'Hunter, Eric', 'Robinson, James E.', 'Gnanakaran, S.', 'Derdeyn, Cynthia A.']",PLoS Pathog,,,False
f117152847c55af7a94ce6953a96e7d3f056c216,PMC,Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways,http://dx.doi.org/10.1371/journal.ppat.1000594,PMC2741593,19763269,CC0,"One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.",2009 Sep 18,"['Rong, Rong', 'Li, Bing', 'Lynch, Rebecca M.', 'Haaland, Richard E.', 'Murphy, Megan K.', 'Mulenga, Joseph', 'Allen, Susan A.', 'Pinter, Abraham', 'Shaw, George M.', 'Hunter, Eric', 'Robinson, James E.', 'Gnanakaran, S.', 'Derdeyn, Cynthia A.']",PLoS Pathog,,,False
4f586b0b5a0c46d2b3e3079ed5d4f15ddbc44496,PMC,Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways,http://dx.doi.org/10.1371/journal.ppat.1000594,PMC2741593,19763269,CC0,"One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.",2009 Sep 18,"['Rong, Rong', 'Li, Bing', 'Lynch, Rebecca M.', 'Haaland, Richard E.', 'Murphy, Megan K.', 'Mulenga, Joseph', 'Allen, Susan A.', 'Pinter, Abraham', 'Shaw, George M.', 'Hunter, Eric', 'Robinson, James E.', 'Gnanakaran, S.', 'Derdeyn, Cynthia A.']",PLoS Pathog,,,False
f631f484f2f69474e722bfbe18a51b3957ff1047,PMC,Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways,http://dx.doi.org/10.1371/journal.ppat.1000594,PMC2741593,19763269,CC0,"One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.",2009 Sep 18,"['Rong, Rong', 'Li, Bing', 'Lynch, Rebecca M.', 'Haaland, Richard E.', 'Murphy, Megan K.', 'Mulenga, Joseph', 'Allen, Susan A.', 'Pinter, Abraham', 'Shaw, George M.', 'Hunter, Eric', 'Robinson, James E.', 'Gnanakaran, S.', 'Derdeyn, Cynthia A.']",PLoS Pathog,,,False
178363fb71ad0ae91e621e6e51fc03bb521f5695,PMC,Crystal Structure of the N-Acetylmannosamine Kinase Domain of GNE,http://dx.doi.org/10.1371/journal.pone.0007165,PMC2742894,19841673,CC BY,"BACKGROUND: UDP-GlcNAc 2-epimerase/ManNAc 6-kinase, GNE, is a bi-functional enzyme that plays a key role in sialic acid biosynthesis. Mutations of the GNE protein cause sialurea or autosomal recessive inclusion body myopathy/Nonaka myopathy. GNE is the only human protein that contains a kinase domain belonging to the ROK (repressor, ORF, kinase) family. PRINCIPAL FINDINGS: We solved the structure of the GNE kinase domain in the ligand-free state. The protein exists predominantly as a dimer in solution, with small populations of monomer and higher-order oligomer in equilibrium with the dimer. Crystal packing analysis reveals the existence of a crystallographic hexamer, and that the kinase domain dimerizes through the C-lobe subdomain. Mapping of disease-related missense mutations onto the kinase domain structure revealed that the mutation sites could be classified into four different groups based on the location – dimer interface, interlobar helices, protein surface, or within other secondary structural elements. CONCLUSIONS: The crystal structure of the kinase domain of GNE provides a structural basis for understanding disease-causing mutations and a model of hexameric wild type full length enzyme. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.",2009 Oct 20,"['Tong, Yufeng', 'Tempel, Wolfram', 'Nedyalkova, Lyudmila', 'MacKenzie, Farrell', 'Park, Hee-Won']",PLoS One,,,True
7f37a4d0fbe40b259fc13a04449eec3983d45c4e,PMC,Crystal Structure of the N-Acetylmannosamine Kinase Domain of GNE,http://dx.doi.org/10.1371/journal.pone.0007165,PMC2742894,19841673,CC BY,"BACKGROUND: UDP-GlcNAc 2-epimerase/ManNAc 6-kinase, GNE, is a bi-functional enzyme that plays a key role in sialic acid biosynthesis. Mutations of the GNE protein cause sialurea or autosomal recessive inclusion body myopathy/Nonaka myopathy. GNE is the only human protein that contains a kinase domain belonging to the ROK (repressor, ORF, kinase) family. PRINCIPAL FINDINGS: We solved the structure of the GNE kinase domain in the ligand-free state. The protein exists predominantly as a dimer in solution, with small populations of monomer and higher-order oligomer in equilibrium with the dimer. Crystal packing analysis reveals the existence of a crystallographic hexamer, and that the kinase domain dimerizes through the C-lobe subdomain. Mapping of disease-related missense mutations onto the kinase domain structure revealed that the mutation sites could be classified into four different groups based on the location – dimer interface, interlobar helices, protein surface, or within other secondary structural elements. CONCLUSIONS: The crystal structure of the kinase domain of GNE provides a structural basis for understanding disease-causing mutations and a model of hexameric wild type full length enzyme. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.",2009 Oct 20,"['Tong, Yufeng', 'Tempel, Wolfram', 'Nedyalkova, Lyudmila', 'MacKenzie, Farrell', 'Park, Hee-Won']",PLoS One,,,False
5aa7bb757f909abc71347a4add89dcdde3f9b7b1,PMC,Inducible Bronchus-Associated Lymphoid Tissue Elicited by a Protein Cage Nanoparticle Enhances Protection in Mice against Diverse Respiratory Viruses,http://dx.doi.org/10.1371/journal.pone.0007142,PMC2743193,19774076,CC BY,"BACKGROUND: Destruction of the architectural and subsequently the functional integrity of the lung following pulmonary viral infections is attributable to both the extent of pathogen replication and to the host-generated inflammation associated with the recruitment of immune responses. The presence of antigenically disparate pulmonary viruses and the emergence of novel viruses assures the recurrence of lung damage with infection and resolution of each primary viral infection. Thus, there is a need to develop safe broad spectrum immunoprophylactic strategies capable of enhancing protective immune responses in the lung but which limits immune-mediated lung damage. The immunoprophylactic strategy described here utilizes a protein cage nanoparticle (PCN) to significantly accelerate clearance of diverse respiratory viruses after primary infection and also results in a host immune response that causes less lung damage. METHODOLOGY/PRINCIPAL FINDINGS: Mice pre-treated with PCN, independent of any specific viral antigens, were protected against both sub-lethal and lethal doses of two different influenza viruses, a mouse-adapted SARS-coronavirus, or mouse pneumovirus. Treatment with PCN significantly increased survival and was marked by enhanced viral clearance, accelerated induction of viral-specific antibody production, and significant decreases in morbidity and lung damage. The enhanced protection appears to be dependent upon the prior development of inducible bronchus-associated lymphoid tissue (iBALT) in the lung in response to the PCN treatment and to be mediated through CD4+ T cell and B cell dependent mechanisms. CONCLUSIONS/SIGNIFICANCE: The immunoprophylactic strategy described utilizes an infection-independent induction of naturally occurring iBALT prior to infection by a pulmonary viral pathogen. This strategy non-specifically enhances primary immunity to respiratory viruses and is not restricted by the antigen specificities inherent in typical vaccination strategies. PCN treatment is asymptomatic in its application and importantly, ameliorates the damaging inflammation normally associated with the recruitment of immune responses into the lung.",2009 Sep 23,"['Wiley, James A.', 'Richert, Laura E.', 'Swain, Steve D.', 'Harmsen, Ann', 'Barnard, Dale L.', 'Randall, Troy D.', 'Jutila, Mark', 'Douglas, Trevor', 'Broomell, Chris', 'Young, Mark', 'Harmsen, Allen']",PLoS One,,,True
f43e2e8087f69f1fd27714d2f600d66321d8f0e9,PMC,"Optimism/pessimism and health-related quality of life during pregnancy across three continents: a matched cohort study in China, Ghana, and the United States",http://dx.doi.org/10.1186/1471-2393-9-39,PMC2744663,19723332,CC BY,"BACKGROUND: Little is known about how optimism/pessimism and health-related quality of life compare across cultures. METHODS: Three samples of pregnant women in their final trimester were recruited from China, Ghana, and the United States (U.S.). Participants completed a survey that included the Life Orientation Test - Revised (LOT-R, an optimism/pessimism measure), the Short Form 12 (SF-12, a quality of life measure), and questions addressing health and demographic factors. A three-country set was created for analysis by matching women on age, gestational age at enrollment, and number of previous pregnancies. Anovas with post-hoc pairwise comparisons were used to compare results across the cohorts. Multivariate regression analysis was used to create a model to identify those variables most strongly associated with optimism/pessimism. RESULTS: LOT-R scores varied significantly across cultures in these samples, with Ghanaian pregnant women being the most optimistic and least pessimistic and Chinese pregnant women being the least optimistic overall and the least pessimistic in subscale analysis. Four key variables predicted approximately 20% of the variance in overall optimism scores: country of origin (p = .006), working for money (p = .05); level of education (p = .002), and ever being treated for emotional issues with medication (p < .001). Quality of life scores also varied by country in these samples, with the most pronounced difference occurring in the vitality measure. U.S. pregnant women reported far lower vitality scores than both Chinese and Ghanaian pregnant women in our sample. CONCLUSION: This research raises important questions regarding what it is about country of origin that so strongly influences optimism/pessimism among pregnant women. Further research is warranted exploring underlying conceptualization of optimism/pessimism and health related quality of life across countries.",2009 Sep 1,"['Moyer, Cheryl A', 'Yang, Huixia', 'Kwawukume, Yao', 'Gupta, Anu', 'Zhu, YuChun', 'Koranteng, Isaac', 'Elsayed, Yasmin', 'Wei, YuMei', 'Greene, Jonathan', 'Calhoun, Cecilia', 'Ekpo, Geraldine', 'Beems, Megan', 'Ryan, Megan', 'Adanu, Richard', 'Anderson, Frank']",BMC Pregnancy Childbirth,,,True
589bb887a113e04b714724a7ec3589037449dc39,PMC,RNase L Mediated Protection from Virus Induced Demyelination,http://dx.doi.org/10.1371/journal.ppat.1000602,PMC2745574,19798426,CC BY,"IFN-α/β plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-α/β dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-α/β pathway through RNA degradation intermediates. Infection of RNase L deficient (RL(−/−)) mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-α/β expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL(−/−) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-α/β mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination.",2009 Oct 2,"['Ireland, Derek D. C.', 'Stohlman, Stephen A.', 'Hinton, David R.', 'Kapil, Parul', 'Silverman, Robert H.', 'Atkinson, Roscoe A.', 'Bergmann, Cornelia C.']",PLoS Pathog,,,True
561bde3336a2cd2006251effb54e5428c4edf3b9,PMC,Systems Integration of Biodefense Omics Data for Analysis of Pathogen-Host Interactions and Identification of Potential Targets,http://dx.doi.org/10.1371/journal.pone.0007162,PMC2745575,19779614,CC BY,"The NIAID (National Institute for Allergy and Infectious Diseases) Biodefense Proteomics program aims to identify targets for potential vaccines, therapeutics, and diagnostics for agents of concern in bioterrorism, including bacterial, parasitic, and viral pathogens. The program includes seven Proteomics Research Centers, generating diverse types of pathogen-host data, including mass spectrometry, microarray transcriptional profiles, protein interactions, protein structures and biological reagents. The Biodefense Resource Center (www.proteomicsresource.org) has developed a bioinformatics framework, employing a protein-centric approach to integrate and support mining and analysis of the large and heterogeneous data. Underlying this approach is a data warehouse with comprehensive protein + gene identifier and name mappings and annotations extracted from over 100 molecular databases. Value-added annotations are provided for key proteins from experimental findings using controlled vocabulary. The availability of pathogen and host omics data in an integrated framework allows global analysis of the data and comparisons across different experiments and organisms, as illustrated in several case studies presented here. (1) The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells) infected by different bacterial (Bacillus anthracis and Salmonella typhimurium) and viral (orthopox) pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. (2) The analysis of a vaccinia-human protein interaction network supplemented with protein accumulation levels led to the identification of human Keratin, type II cytoskeletal 4 protein as a potential therapeutic target. (3) Comparison of complete genomes from pathogenic variants coupled with experimental information on complete proteomes allowed the identification and prioritization of ten potential diagnostic targets from Bacillus anthracis. The integrative analysis across data sets from multiple centers can reveal potential functional significance and hidden relationships between pathogen and host proteins, thereby providing a systems approach to basic understanding of pathogenicity and target identification.",2009 Sep 25,"['McGarvey, Peter B.', 'Huang, Hongzhan', 'Mazumder, Raja', 'Zhang, Jian', 'Chen, Yongxing', 'Zhang, Chengdong', 'Cammer, Stephen', 'Will, Rebecca', 'Odle, Margie', 'Sobral, Bruno', 'Moore, Margaret', 'Wu, Cathy H.']",PLoS One,,,True
c6fde7aab8fedbe212cac83d89064d4fb74089b9,PMC,Emerging Technologies for the Detection of Rabies Virus: Challenges and Hopes in the 21st Century,http://dx.doi.org/10.1371/journal.pntd.0000530,PMC2745658,19787037,CC BY,"The diagnosis of rabies is routinely based on clinical and epidemiological information, especially when exposures are reported in rabies-endemic countries. Diagnostic tests using conventional assays that appear to be negative, even when undertaken late in the disease and despite the clinical diagnosis, have a tendency, at times, to be unreliable. These tests are rarely optimal and entirely dependent on the nature and quality of the sample supplied. In the course of the past three decades, the application of molecular biology has aided in the development of tests that result in a more rapid detection of rabies virus. These tests enable viral strain identification from clinical specimens. Currently, there are a number of molecular tests that can be used to complement conventional tests in rabies diagnosis. Indeed the challenges in the 21st century for the development of rabies diagnostics are not of a technical nature; these tests are available now. The challenges in the 21st century for diagnostic test developers are two-fold: firstly, to achieve internationally accepted validation of a test that will then lead to its acceptance by organisations globally. Secondly, the areas of the world where such tests are needed are mainly in developing regions where financial and logistical barriers prevent their implementation. Although developing countries with a poor healthcare infrastructure recognise that molecular-based diagnostic assays will be unaffordable for routine use, the cost/benefit ratio should still be measured. Adoption of rapid and affordable rabies diagnostic tests for use in developing countries highlights the importance of sharing and transferring technology through laboratory twinning between the developed and the developing countries. Importantly for developing countries, the benefit of molecular methods as tools is the capability for a differential diagnosis of human diseases that present with similar clinical symptoms. Antemortem testing for human rabies is now possible using molecular techniques. These barriers are not insurmountable and it is our expectation that if such tests are accepted and implemented where they are most needed, they will provide substantial improvements for rabies diagnosis and surveillance. The advent of molecular biology and new technological initiatives that combine advances in biology with other disciplines will support the development of techniques capable of high throughput testing with a low turnaround time for rabies diagnosis.",2009 Sep 29,"['Fooks, Anthony R.', 'Johnson, Nicholas', 'Freuling, Conrad M.', 'Wakeley, Philip R.', 'Banyard, Ashley C.', 'McElhinney, Lorraine M.', 'Marston, Denise A.', 'Dastjerdi, Akbar', 'Wright, Edward', 'Weiss, Robin A.', 'Müller, Thomas']",PLoS Negl Trop Dis,,,True
c9df58c92109a1057c10b24867cb3566ffb46408,PMC,Prospects for control of emerging infectious diseases with plasmid DNA vaccines,http://dx.doi.org/10.1186/1476-8518-7-3,PMC2746192,19735569,CC BY,"Experiments almost 20 years ago demonstrated that injections of a sequence of DNA encoding part of a pathogen could stimulate immunity. It was soon realized that ""DNA vaccination"" had numerous potential advantages over conventional vaccine approaches including inherent safety and a more rapid production time. These and other attributes make DNA vaccines ideal for development against emerging pathogens. Recent advances in optimizing various aspects of DNA vaccination have accelerated this approach from concept to reality in contemporary human trials. Although not yet licensed for human use, several DNA vaccines have now been approved for animal health indications. The rapid manufacturing capabilities of DNA vaccines may be particularly important for emerging infectious diseases including the current novel H1N1 Influenza A pandemic, where pre-existing immunity is limited. Because of recent advances in DNA vaccination, this approach has the potential to be a powerful new weapon in protecting against emerging and potentially pandemic human pathogens.",2009 Sep 7,"Moss, Ronald B",J Immune Based Ther Vaccines,,,True
de4ab44a9e3ff11c0f831a0ab5a421191c78c6dc,PMC,Nationwide epidemiological study of severe gallstone disease in Taiwan,http://dx.doi.org/10.1186/1471-230X-9-63,PMC2746226,19698126,CC BY,"BACKGROUND: Our study aimed to assess the nationwide trends in the incidence of severe gallstone disease in Taiwan among adults aged ≥20. METHODS: A retrospective longitudinal study was conducted using Taiwan National Health Insurance Research Database collected during 1997–2005. Patients with incident severe gallstone disease (acute cholecystitis, biliary pancreatitis, acute cholangitis) and gallstone-related procedures (elective and non-elective cholecystectomy, endoscopic retrograde cholangiopancreatography [ERCP]) that led to hospital admission were identified using ICD-9-CM diagnostic and procedure codes. Annual incidence rates of gallstone-related complications and procedures were calculated and their 95% confidence intervals (CI) were estimated assuming a Poisson distribution. RESULTS: The hospital admission rate for severe gallstone disease increased with advancing age and the age-standardized rate (95% CI) per 1000 population was 0.60 (0.59–0.60) for men and 0.59 (0.59–0.60) for women. Men had a higher rate of acute cholecystitis, probably due to the substantially lower rate of elective cholecystectomy among men than women. For those aged 20–39, hospital admissions for all gallstone-related complications and procedures increased significantly. For those aged ≥60, incidences of biliary pancreatitis, acute cholangitis, and hospital admission for gallstone receiving ERCP increased significantly without substantial change in the incidence of acute cholecystitis and despite a decreased rate of elective cholecystectomy. CONCLUSION: This population-based study found a substantial increase in the rate of admission for severe gallstone disease among those aged 20–39. Concurrently, the incidences of biliary pancreatitis and acute cholangitis have risen among those aged ≥60.",2009 Aug 22,"['Huang, John', 'Chang, Chia-Hsuin', 'Wang, Juin-Ling', 'Kuo, Hsu-Ko', 'Lin, Jou-Wei', 'Shau, Wen-Yi', 'Lee, Po-Huang']",BMC Gastroenterol,,,True
2a8339ac2c0891d5113f221ebd214f2b1d903d38,PMC,High quality protein microarray using in situ protein purification,http://dx.doi.org/10.1186/1472-6750-9-72,PMC2746808,19698181,CC BY,"BACKGROUND: In the postgenomic era, high throughput protein expression and protein microarray technologies have progressed markedly permitting screening of therapeutic reagents and discovery of novel protein functions. Hexa-histidine is one of the most commonly used fusion tags for protein expression due to its small size and convenient purification via immobilized metal ion affinity chromatography (IMAC). This purification process has been adapted to the protein microarray format, but the quality of in situ His-tagged protein purification on slides has not been systematically evaluated. We established methods to determine the level of purification of such proteins on metal chelate-modified slide surfaces. Optimized in situ purification of His-tagged recombinant proteins has the potential to become the new gold standard for cost-effective generation of high-quality and high-density protein microarrays. RESULTS: Two slide surfaces were examined, chelated Cu(2+ )slides suspended on a polyethylene glycol (PEG) coating and chelated Ni(2+ )slides immobilized on a support without PEG coating. Using PEG-coated chelated Cu(2+ )slides, consistently higher purities of recombinant proteins were measured. An optimized wash buffer (PBST) composed of 10 mM phosphate buffer, 2.7 mM KCl, 140 mM NaCl and 0.05% Tween 20, pH 7.4, further improved protein purity levels. Using Escherichia coli cell lysates expressing 90 recombinant Streptococcus pneumoniae proteins, 73 proteins were successfully immobilized, and 66 proteins were in situ purified with greater than 90% purity. We identified several antigens among the in situ-purified proteins via assays with anti-S. pneumoniae rabbit antibodies and a human patient antiserum, as a demonstration project of large scale microarray-based immunoproteomics profiling. The methodology is compatible with higher throughput formats of in vivo protein expression, eliminates the need for resin-based purification and circumvents protein solubility and denaturation problems caused by buffer exchange steps and freeze-thaw cycles, which are associated with resin-based purification, intermittent protein storage and deposition on microarrays. CONCLUSION: An optimized platform for in situ protein purification on microarray slides using His-tagged recombinant proteins is a desirable tool for the screening of novel protein functions and protein-protein interactions. In the context of immunoproteomics, such protein microarrays are complimentary to approaches using non-recombinant methods to discover and characterize bacterial antigens.",2009 Aug 23,"['Kwon, Keehwan', 'Grose, Carissa', 'Pieper, Rembert', 'Pandya, Gagan A', 'Fleischmann, Robert D', 'Peterson, Scott N']",BMC Biotechnol,,,True
d0d3db0b7401dbecdab05576f43883e00fbd41db,PMC,High quality protein microarray using in situ protein purification,http://dx.doi.org/10.1186/1472-6750-9-72,PMC2746808,19698181,CC BY,"BACKGROUND: In the postgenomic era, high throughput protein expression and protein microarray technologies have progressed markedly permitting screening of therapeutic reagents and discovery of novel protein functions. Hexa-histidine is one of the most commonly used fusion tags for protein expression due to its small size and convenient purification via immobilized metal ion affinity chromatography (IMAC). This purification process has been adapted to the protein microarray format, but the quality of in situ His-tagged protein purification on slides has not been systematically evaluated. We established methods to determine the level of purification of such proteins on metal chelate-modified slide surfaces. Optimized in situ purification of His-tagged recombinant proteins has the potential to become the new gold standard for cost-effective generation of high-quality and high-density protein microarrays. RESULTS: Two slide surfaces were examined, chelated Cu(2+ )slides suspended on a polyethylene glycol (PEG) coating and chelated Ni(2+ )slides immobilized on a support without PEG coating. Using PEG-coated chelated Cu(2+ )slides, consistently higher purities of recombinant proteins were measured. An optimized wash buffer (PBST) composed of 10 mM phosphate buffer, 2.7 mM KCl, 140 mM NaCl and 0.05% Tween 20, pH 7.4, further improved protein purity levels. Using Escherichia coli cell lysates expressing 90 recombinant Streptococcus pneumoniae proteins, 73 proteins were successfully immobilized, and 66 proteins were in situ purified with greater than 90% purity. We identified several antigens among the in situ-purified proteins via assays with anti-S. pneumoniae rabbit antibodies and a human patient antiserum, as a demonstration project of large scale microarray-based immunoproteomics profiling. The methodology is compatible with higher throughput formats of in vivo protein expression, eliminates the need for resin-based purification and circumvents protein solubility and denaturation problems caused by buffer exchange steps and freeze-thaw cycles, which are associated with resin-based purification, intermittent protein storage and deposition on microarrays. CONCLUSION: An optimized platform for in situ protein purification on microarray slides using His-tagged recombinant proteins is a desirable tool for the screening of novel protein functions and protein-protein interactions. In the context of immunoproteomics, such protein microarrays are complimentary to approaches using non-recombinant methods to discover and characterize bacterial antigens.",2009 Aug 23,"['Kwon, Keehwan', 'Grose, Carissa', 'Pieper, Rembert', 'Pandya, Gagan A', 'Fleischmann, Robert D', 'Peterson, Scott N']",BMC Biotechnol,,,False
c8eb13b64a5392a43ac16027e68b30573a9d0df0,PMC,Validation of a short form Wisconsin Upper Respiratory Symptom Survey (WURSS-21),http://dx.doi.org/10.1186/1477-7525-7-76,PMC2748069,19674476,CC BY,"BACKGROUND: The Wisconsin Upper Respiratory Symptom Survey (WURSS) is an illness-specific health-related quality-of-life questionnaire outcomes instrument. OBJECTIVES: Research questions were: 1) How well does the WURSS-21 assess the symptoms and functional impairments associated with common cold? 2) How well can this instrument measure change over time (responsiveness)? 3) What is the minimal important difference (MID) that can be detected by the WURSS-21? 4) What are the descriptive statistics for area under the time severity curve (AUC)? 5) What sample sizes would trials require to detect MID or AUC criteria? 6) What does factor analysis tell us about the underlying dimensional structure of the common cold? 7) How reliable are items, domains, and summary scores represented in WURSS? 8) For each of these considerations, how well does the WURSS-21 compare to the WURSS-44, Jackson, and SF-8? STUDY DESIGN AND SETTING: People with Jackson-defined colds were recruited from the community in and around Madison, Wisconsin. Participants were enrolled within 48 hours of first cold symptom and monitored for up to 14 days of illness. Half the sample filled out the WURSS-21 in the morning and the WURSS-44 in the evening, with the other half reversing the daily order. External comparators were the SF-8, a 24-hour recall general health measure yielding separate physical and mental health scores, and the eight-item Jackson cold index, which assesses symptoms, but not functional impairment or quality of life. RESULTS: In all, 230 participants were monitored for 2,457 person-days. Participants were aged 14 to 83 years (mean 34.1, SD 13.6), majority female (66.5%), mostly white (86.0%), and represented substantive education and income diversity. WURSS-21 items demonstrated similar performance when embedded within the WURSS-44 or in the stand-alone WURSS-21. Minimal important difference (MID) and Guyatt's responsiveness index were 10.3, 0.71 for the WURSS-21 and 18.5, 0.75 for the WURSS-44. Factorial analysis suggested an eight dimension structure for the WURSS-44 and a three dimension structure for the WURSS-21, with composite reliability coefficients ranging from 0.87 to 0.97, and Cronbach's alpha ranging from 0.76 to 0.96. Both WURSS versions correlated significantly with the Jackson scale (W-21 R = 0.85; W-44 R = 0.88), with the SF-8 physical health (W-21 R = -0.79; W-44 R = -0.80) and SF-8 mental health (W-21 R = -0.55; W-44 R = -0.60). CONCLUSION: The WURSS-44 and WURSS-21 perform well as illness-specific quality-of-life evaluative outcome instruments. Construct validity is supported by the data presented here. While the WURSS-44 covers more symptoms, the WURSS-21 exhibits similar performance in terms of reliability, responsiveness, importance-to-patients, and convergence with other measures.",2009 Aug 12,"['Barrett, Bruce', 'Brown, Roger L', 'Mundt, Marlon P', 'Thomas, Gay R', 'Barlow, Shari K', 'Highstrom, Alex D', 'Bahrainian, Mozhdeh']",Health Qual Life Outcomes,,,True
38f12e7be8d0f29aabe77ac96fa19d62407c0898,PMC,A case for a CUG-initiated coding sequence overlapping torovirus ORF1a and encoding a novel 30 kDa product,http://dx.doi.org/10.1186/1743-422X-6-136,PMC2749830,19737402,CC BY,"The genus Torovirus (order Nidovirales) includes a number of species that infect livestock. These viruses have a linear positive-sense ssRNA genome of ~25-30 kb, encoding a large polyprotein that is expressed from the genomic RNA, and several additional proteins expressed from a nested set of 3'-coterminal subgenomic RNAs. In this brief report, we describe the bioinformatic discovery of a new, apparently coding, ORF that overlaps the 5' end of the polyprotein coding sequence, ORF1a, in the +2 reading frame. The new ORF has a strong coding signature and, in fact, is more conserved at the amino acid level than the overlapping region of ORF1a. We propose that the new ORF utilizes a non-AUG initiation codon - namely a conserved CUG codon in a strong Kozak context - upstream of the ORF1a AUG initiation codon, resulting in a novel 258 amino acid protein, dubbed '30K'.",2009 Sep 8,"['Firth, Andrew E', 'Atkins, John F']",Virol J,,,True
3bac7494aeafbb2f2cff25690dac67e99c120029,PMC,Development of a fluorescent quantitative real-time polymerase chain reaction assay for the detection of Goose parvovirus in vivo,http://dx.doi.org/10.1186/1743-422X-6-142,PMC2751755,19754946,CC BY,"BACKGROUND: Goose parvovirus (GPV) is a Dependovirus associated with latent infection and mortality in geese. Currently, it severely affects geese production worldwide. The objective of this study was to develop a fluorescent quantitative real-time polymerase chain reaction (PCR) (FQ-PCR) assay for fast and accurate quantification of GPV DNA in infected goslings, which can aid in the understanding of the regular distribution pattern and the nosogenesis of GPV in vivo. RESULTS: The detection limit of the assay was 2.8 × 10(1 )standard DNA copies, with a sensitivity of 3 logs higher than that of the conventional gel-based PCR assay targeting the same gene. The real-time PCR was reproducible, as shown by satisfactory low intraassay and interassay coefficients of variation. CONCLUSION: The high sensitivity, specificity, simplicity, and reproducibility of the GPV fluorogenic PCR assay, combined with a high throughput, make this method suitable for a broad spectrum of GPV etiology-related applications.",2009 Sep 15,"['Yang, Jin-Long', 'Cheng, An-Chun', 'Wang, Ming-Shu', 'Pan, Kang-Cheng', 'Li, Min', 'Guo, Yu-Fei', 'Li, Chuan-Feng', 'Zhu, De-Kang', 'Chen, Xiao-Yue']",Virol J,,,True
9a1ed211481f2c4e15f48ec3f712e73901eb628a,PMC,The Key Role of Genomics in Modern Vaccine and Drug Design for Emerging Infectious Diseases,http://dx.doi.org/10.1371/journal.pgen.1000612,PMC2752168,19855822,CC BY,"It can be argued that the arrival of the “genomics era” has significantly shifted the paradigm of vaccine and therapeutics development from microbiological to sequence-based approaches. Genome sequences provide a previously unattainable route to investigate the mechanisms that underpin pathogenesis. Genomics, transcriptomics, metabolomics, structural genomics, proteomics, and immunomics are being exploited to perfect the identification of targets, to design new vaccines and drugs, and to predict their effects in patients. Furthermore, human genomics and related studies are providing insights into aspects of host biology that are important in infectious disease. This ever-growing body of genomic data and new genome-based approaches will play a critical role in the future to enable timely development of vaccines and therapeutics to control emerging infectious diseases.",2009 Oct 26,"['Seib, Kate L.', 'Dougan, Gordon', 'Rappuoli, Rino']",PLoS Genet,,,True
0d12fa6f695fdb75443b00c49514e7850ef461e5,PMC,Functional Genetic Variants in DC-SIGNR Are Associated with Mother-to-Child Transmission of HIV-1,http://dx.doi.org/10.1371/journal.pone.0007211,PMC2752805,19809496,CC BY,"BACKGROUND: Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Given that the C-type lectin receptor, dendritic cell-specific ICAM-grabbing non-integrin-related (DC-SIGNR, also known as CD209L or liver/lymph node–specific ICAM-grabbing non-integrin (L-SIGN)), can interact with pathogens including HIV-1 and is expressed at the maternal-fetal interface, we hypothesized that it could influence MTCT of HIV-1. METHODS AND FINDINGS: To investigate the potential role of DC-SIGNR in MTCT of HIV-1, we carried out a genetic association study of DC-SIGNR in a well-characterized cohort of 197 HIV-infected mothers and their infants recruited in Harare, Zimbabwe. Infants harbouring two copies of DC-SIGNR H1 and/or H3 haplotypes (H1-H1, H1-H3, H3-H3) had a 3.6-fold increased risk of in utero (IU) (P = 0.013) HIV-1 infection and a 5.7-fold increased risk of intrapartum (IP) (P = 0.025) HIV-1 infection after adjusting for a number of maternal factors. The implicated H1 and H3 haplotypes share two single nucleotide polymorphisms (SNPs) in promoter region (p-198A) and intron 2 (int2-180A) that were associated with increased risk of both IU (P = 0.045 and P = 0.003, respectively) and IP (P = 0.025, for int2-180A) HIV-1 infection. The promoter variant reduced transcriptional activity in vitro. In homozygous H1 infants bearing both the p-198A and int2-180A mutations, we observed a 4-fold decrease in the level of placental DC-SIGNR transcripts, disproportionately affecting the expression of membrane-bound isoforms compared to infant noncarriers (P = 0.011). CONCLUSION: These results suggest that DC-SIGNR plays a crucial role in MTCT of HIV-1 and that impaired placental DC-SIGNR expression increases risk of transmission.",2009 Oct 7,"['Boily-Larouche, Geneviève', 'Iscache, Anne-Laure', 'Zijenah, Lynn S.', 'Humphrey, Jean H.', 'Mouland, Andrew J.', 'Ward, Brian J.', 'Roger, Michel']",PLoS One,,,True
0f157fb0a719dd0d52fb921fb1369ccb6477636e,PMC,Proteomics computational analyses suggest that the bornavirus glycoprotein is a class III viral fusion protein (γ penetrene),http://dx.doi.org/10.1186/1743-422X-6-145,PMC2753318,19765297,CC BY,"BACKGROUND: Borna disease virus (BDV) is the type member of the Bornaviridae, a family of viruses that induce often fatal neurological diseases in horses, sheep and other animals, and have been proposed to have roles in certain psychiatric diseases of humans. The BDV glycoprotein (G) is an extensively glycosylated protein that migrates with an apparent molecular mass of 84,000 to 94,000 kilodaltons (kDa). BDV G is post-translationally cleaved by the cellular subtilisin-like protease furin into two subunits, a 41 kDa amino terminal protein GP1 and a 43 kDa carboxyl terminal protein GP2. RESULTS: Class III viral fusion proteins (VFP) encoded by members of the Rhabdoviridae, Herpesviridae and Baculoviridae have an internal fusion domain comprised of beta sheets, other beta sheet domains, an extended alpha helical domain, a membrane proximal stem domain and a carboxyl terminal anchor. Proteomics computational analyses suggest that the structural/functional motifs that characterize class III VFP are located collinearly in BDV G. Structural models were established for BDV G based on the post-fusion structure of a prototypic class III VFP, vesicular stomatitis virus glycoprotein (VSV G). CONCLUSION: These results suggest that G encoded by members of the Bornavirdae are class III VFPs (gamma-penetrenes).",2009 Sep 18,"['Garry, Courtney E', 'Garry, Robert F']",Virol J,,,True
8c78151fa23bf78cc20b2e2c5c0b47d79d12a1a6,PMC,An effective docking strategy for virtual screening based on multi-objective optimization algorithm,http://dx.doi.org/10.1186/1471-2105-10-58,PMC2753843,19210777,CC BY,"BACKGROUND: Development of a fast and accurate scoring function in virtual screening remains a hot issue in current computer-aided drug research. Different scoring functions focus on diverse aspects of ligand binding, and no single scoring can satisfy the peculiarities of each target system. Therefore, the idea of a consensus score strategy was put forward. Integrating several scoring functions, consensus score re-assesses the docked conformations using a primary scoring function. However, it is not really robust and efficient from the perspective of optimization. Furthermore, to date, the majority of available methods are still based on single objective optimization design. RESULTS: In this paper, two multi-objective optimization methods, called MOSFOM, were developed for virtual screening, which simultaneously consider both the energy score and the contact score. Results suggest that MOSFOM can effectively enhance enrichment and performance compared with a single score. For three different kinds of binding sites, MOSFOM displays an excellent ability to differentiate active compounds through energy and shape complementarity. EFMOGA performed particularly well in the top 2% of database for all three cases, whereas MOEA_Nrg and MOEA_Cnt performed better than the corresponding individual scoring functions if the appropriate type of binding site was selected. CONCLUSION: The multi-objective optimization method was successfully applied in virtual screening with two different scoring functions that can yield reasonable binding poses and can furthermore, be ranked with the potentially compromised conformations of each compound, abandoning those conformations that can not satisfy overall objective functions.",2009 Feb 11,"['Li, Honglin', 'Zhang, Hailei', 'Zheng, Mingyue', 'Luo, Jie', 'Kang, Ling', 'Liu, Xiaofeng', 'Wang, Xicheng', 'Jiang, Hualiang']",BMC Bioinformatics,,,True
73687cb6e2232dce920704c44684080babf9cbfa,PMC,An effective docking strategy for virtual screening based on multi-objective optimization algorithm,http://dx.doi.org/10.1186/1471-2105-10-58,PMC2753843,19210777,CC BY,"BACKGROUND: Development of a fast and accurate scoring function in virtual screening remains a hot issue in current computer-aided drug research. Different scoring functions focus on diverse aspects of ligand binding, and no single scoring can satisfy the peculiarities of each target system. Therefore, the idea of a consensus score strategy was put forward. Integrating several scoring functions, consensus score re-assesses the docked conformations using a primary scoring function. However, it is not really robust and efficient from the perspective of optimization. Furthermore, to date, the majority of available methods are still based on single objective optimization design. RESULTS: In this paper, two multi-objective optimization methods, called MOSFOM, were developed for virtual screening, which simultaneously consider both the energy score and the contact score. Results suggest that MOSFOM can effectively enhance enrichment and performance compared with a single score. For three different kinds of binding sites, MOSFOM displays an excellent ability to differentiate active compounds through energy and shape complementarity. EFMOGA performed particularly well in the top 2% of database for all three cases, whereas MOEA_Nrg and MOEA_Cnt performed better than the corresponding individual scoring functions if the appropriate type of binding site was selected. CONCLUSION: The multi-objective optimization method was successfully applied in virtual screening with two different scoring functions that can yield reasonable binding poses and can furthermore, be ranked with the potentially compromised conformations of each compound, abandoning those conformations that can not satisfy overall objective functions.",2009 Feb 11,"['Li, Honglin', 'Zhang, Hailei', 'Zheng, Mingyue', 'Luo, Jie', 'Kang, Ling', 'Liu, Xiaofeng', 'Wang, Xicheng', 'Jiang, Hualiang']",BMC Bioinformatics,,,False
670ade9d86b2fb507104d011a048323450e21b59,PMC,Efficient oligonucleotide probe selection for pan-genomic tiling arrays,http://dx.doi.org/10.1186/1471-2105-10-293,PMC2753849,19758451,CC BY,"BACKGROUND: Array comparative genomic hybridization is a fast and cost-effective method for detecting, genotyping, and comparing the genomic sequence of unknown bacterial isolates. This method, as with all microarray applications, requires adequate coverage of probes targeting the regions of interest. An unbiased tiling of probes across the entire length of the genome is the most flexible design approach. However, such a whole-genome tiling requires that the genome sequence is known in advance. For the accurate analysis of uncharacterized bacteria, an array must query a fully representative set of sequences from the species' pan-genome. Prior microarrays have included only a single strain per array or the conserved sequences of gene families. These arrays omit potentially important genes and sequence variants from the pan-genome. RESULTS: This paper presents a new probe selection algorithm (PanArray) that can tile multiple whole genomes using a minimal number of probes. Unlike arrays built on clustered gene families, PanArray uses an unbiased, probe-centric approach that does not rely on annotations, gene clustering, or multi-alignments. Instead, probes are evenly tiled across all sequences of the pan-genome at a consistent level of coverage. To minimize the required number of probes, probes conserved across multiple strains in the pan-genome are selected first, and additional probes are used only where necessary to span polymorphic regions of the genome. The viability of the algorithm is demonstrated by array designs for seven different bacterial pan-genomes and, in particular, the design of a 385,000 probe array that fully tiles the genomes of 20 different Listeria monocytogenes strains with overlapping probes at greater than twofold coverage. CONCLUSION: PanArray is an oligonucleotide probe selection algorithm for tiling multiple genome sequences using a minimal number of probes. It is capable of fully tiling all genomes of a species on a single microarray chip. These unique pan-genome tiling arrays provide maximum flexibility for the analysis of both known and uncharacterized strains.",2009 Sep 16,"['Phillippy, Adam M', 'Deng, Xiangyu', 'Zhang, Wei', 'Salzberg, Steven L']",BMC Bioinformatics,,,True
265121b026dccf527cd9cc00dbd28a425ba5510f,PMC,"Nutritional Status, Breastfeeding, and Evolution of Infants with Acute Viral Bronchiolitis",,PMC2754025,18330067,CC BY,"Acute viral bronchiolitis is a common respiratory infectious disease of infancy. A prospective study was carried out with 175 infants aged up to six months to evaluate their nutritional and breastfeeding status as possible risk factors for unfavourable evolution of previously-healthy infants from a care hospital. Immunofluorescence test for virus and anthropometric assessment were performed. Outcomes were length of oxygen-use, length of hospital stay, and type of hospital unit needed. Seventy-three percent of the infants were well-nourished, 6% undernourished, 8.6% at a nutritional risk, 10.9% overweight, and 1.7% obese. Eighty-one percent of the undernourished and nutritionally at-risk infants and 72% of the well-nourished, overweight, and obese infants did not receive exclusive breastfeeding. The median length of hospital stay was four days and of oxygen-use was 60 hours. The nutritional status did not affect the clinical course of previously-healthy infants with acute viral brochiolitis. The duration of exclusive breastfeeding, but not type of breastfeeding, was inversely related to the length of oxygen-use and the length of hospital stay. Shorter exclusive breastfeeding was observed in infants who were assigned to a paediatric ward or to an intensive care unit. In conclusion, longer duration of breastfeeding was associated with better clinical outcomes.",2007 Sep,"['Dornelles, Cristina T.L.', 'Piva, Jefferson P.', 'Marostica, Paulo J.C.']",J Health Popul Nutr,,,True
fe83b78b82d15a20c4c1b07f472785d851b5f982,PMC,Procalcitonin levels and bacterial aetiology among COPD patients admitted to the ICU with severe pneumonia: a prospective cohort study,http://dx.doi.org/10.1186/1471-2334-9-157,PMC2754485,19772586,CC BY,"BACKGROUND: Serum procalcitonin (PCT) is considered useful in predicting the likeliness of developing bacterial infections in emergency setting. In this study, we describe PCT levels overtime and their relationship with bacterial infection in chronic obstructive pulmonary disease (COPD) critically ill patients with pneumonia. METHODS: We conducted a prospective cohort study in an ICU of a University Hospital. All consecutive COPD patients admitted for pneumonia between September 2005 and September 2006 were included. Respiratory samples were tested for the presence of bacteria and viruses. Procalcitonin was sequentially assessed and patients classified according to the probability of the presence of a bacterial infection. RESULTS: Thirty four patients were included. The PCT levels were assessed in 32/34 patients, median values were: 0.493 μg/L [IQR, 0.131 to 1.471] at the time of admission, 0.724 μg/L [IQR, 0.167 to 2.646] at six hours, and 0.557 μg/L [IQR, 0.123 to 3.4] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 μg/L in 3/32 (9%) patients and greater than 0.25 μg/L in 22/32 (69%) patients, suggesting low and high probability of bacterial infection, respectively. Fifteen bacteria and five viruses were detected in 15/34 (44%) patients. Bacteria were not detected in patients with PCTmax levels < 0.1 μg/L. In contrast, bacteria were detected in 4/7 (57%) patients estimated unlikely to have a bacterial infection by PCT levels (PCTmax > 0.1 and < 0.25 μg/L). CONCLUSION: Based on these results we suggest that a PCT level cut off > 0.1 μg/L may be more appropriate than 0.25 μg/L (previously proposed for non severe lower respiratory tract infection) to predict the probability of a bacterial infection in severe COPD patients with pneumonia. Further studies testing procalcitonin-based antibiotic strategies are needed in COPD patients with severe pneumonia.",2009 Sep 21,"['Daubin, Cédric', 'Parienti, Jean-Jacques', 'Fradin, Sabine', 'Vabret, Astrid', 'Ramakers, Michel', 'Terzi, Nicolas', 'Freymuth, François', 'Charbonneau, Pierre', 'du Cheyron, Damien']",BMC Infect Dis,,,True
3041d890310a050dfc5725636a7b26a23b9d40aa,PMC,The Replicase Gene of Avian Coronavirus Infectious Bronchitis Virus Is a Determinant of Pathogenicity,http://dx.doi.org/10.1371/journal.pone.0007384,PMC2754531,19816578,CC BY,"We have previously demonstrated that the replacement of the S gene from an avirulent strain (Beaudette) of infectious bronchitis virus (IBV) with an S gene from a virulent strain (M41) resulted in a recombinant virus (BeauR-M41(S)) with the in vitro cell tropism of the virulent virus but that was still avirulent. In order to investigate whether any of the other structural or accessory genes played a role in pathogenicity we have now replaced these from the Beaudette strain with those from M41. The recombinant IBV was in effect a chimaeric virus with the replicase gene derived from Beaudette and the rest of the genome from M41. This demonstrated that it is possible to exchange a large region of the IBV genome, approximately 8.4 kb, using our transient dominant selection method. Recovery of a viable recombinant IBV also demonstrated that it is possible to interchange a complete replicase gene as we had in effect replaced the M41 replicase gene with the Beaudette derived gene. Analysis of the chimaeric virus showed that it was avirulent indicating that none of the structural or accessory genes derived from a virulent isolate of IBV were able to restore virulence and that therefore, the loss of virulence associated with the Beaudette strain resides in the replicase gene.",2009 Oct 9,"['Armesto, Maria', 'Cavanagh, Dave', 'Britton, Paul']",PLoS One,,,True
85581e91ad30b4385cbd57496aaaf5f19ff33080,PMC,Computational Resources in Infectious Disease: Limitations and Challenges,http://dx.doi.org/10.1371/journal.pcbi.1000481,PMC2756590,19855825,CC BY,,2009 Oct 26,"['Berglund, Eva C.', 'Nystedt, Björn', 'Andersson, Siv G. E.']",PLoS Comput Biol,,,True
45f1fd0f1962aa8162216270b1a97e57e0708b18,PMC,"The Role of Genomics in the Identification, Prediction, and Prevention of Biological Threats",http://dx.doi.org/10.1371/journal.pbio.1000217,PMC2757898,19855827,CC BY,"In all likelihood, it is only a matter of time before our public health system will face a major biological threat, whether intentionally dispersed or originating from a known or newly emerging infectious disease. It is necessary not only to increase our reactive “biodefense,” but also to be proactive and increase our preparedness. To achieve this goal, it is essential that the scientific and public health communities fully embrace the genomic revolution, and that novel bioinformatic and computing tools necessary to make great strides in our understanding of these novel and emerging threats be developed. Genomics has graduated from a specialized field of science to a research tool that soon will be routine in research laboratories and clinical settings. Because the technology is becoming more affordable, genomics can and should be used proactively to build our preparedness and responsiveness to biological threats. All pieces, including major continued funding, advances in next-generation sequencing technologies, bioinformatics infrastructures, and open access to data and metadata, are being set in place for genomics to play a central role in our public health system.",2009 Oct 26,"['Fricke, W. Florian', 'Rasko, David A.', 'Ravel, Jacques']",PLoS Biol,,,True
02974b9466bf593193d05ada669d7ff0567bb657,PMC,Can an Infectious Disease Genomics Project Predict and Prevent the Next Pandemic?,http://dx.doi.org/10.1371/journal.pbio.1000219,PMC2757903,19855828,CC BY,Infectious diseases need a globally coordinated genomic-based movement linking sequencing efforts to development of response tools to mitigate the impact of existing and emerging threats.,2009 Oct 26,"['Gupta, Rajesh', 'Michalski, Mark H.', 'Rijsberman, Frank R.']",PLoS Biol,,,True
f8bd14ffe1272be4d4c25d0d6f23f2479c0d1475,PMC,Inhibition of RNA Recruitment and Replication of an RNA Virus by Acridine Derivatives with Known Anti-Prion Activities,http://dx.doi.org/10.1371/journal.pone.0007376,PMC2757906,19823675,CC BY,"BACKGROUND: Small molecule inhibitors of RNA virus replication are potent antiviral drugs and useful to dissect selected steps in the replication process. To identify antiviral compounds against Tomato bushy stunt virus (TBSV), a model positive stranded RNA virus, we tested acridine derivatives, such as chlorpromazine (CPZ) and quinacrine (QC), which are active against prion-based diseases. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that CPZ and QC compounds inhibited TBSV RNA accumulation in plants and in protoplasts. In vitro assays revealed that the inhibitory effects of these compounds were manifested at different steps of TBSV replication. QC was shown to have an effect on multiple steps, including: (i) inhibition of the selective binding of the p33 replication protein to the viral RNA template, which is required for recruitment of viral RNA for replication; (ii) reduction of minus-strand synthesis by the tombusvirus replicase; and (iii) inhibition of translation of the uncapped TBSV genomic RNA. In contrast, CPZ was shown to inhibit the in vitro assembly of the TBSV replicase, likely due to binding of CPZ to intracellular membranes, which are important for RNA virus replication. CONCLUSION/SIGNIFICANCE: Since we found that CPZ was also an effective inhibitor of other plant viruses, including Tobacco mosaic virus and Turnip crinkle virus, it seems likely that CPZ has a broad range of antiviral activity. Thus, these inhibitors constitute effective tools to study similarities in replication strategies of various RNA viruses.",2009 Oct 13,"['Sasvari, Zsuzsanna', 'Bach, Stéphane', 'Blondel, Marc', 'Nagy, Peter D.']",PLoS One,,,True
341032e0d9e1730bdf19b1742d4f9e32c544d083,PMC,Genomics of Emerging Infectious Disease: A PLoS Collection,http://dx.doi.org/10.1371/journal.pbio.1000224,PMC2757914,19855830,CC BY,,2009 Oct 26,"['Eisen, Jonathan A.', 'MacCallum, Catriona J.']",PLoS Biol,,,True
82ec1cd41017fab2d523840ae9fb3f30dbeeab55,PMC,Up-Regulation of Hepatitis C Virus Replication and Production by Inhibition of MEK/ERK Signaling,http://dx.doi.org/10.1371/journal.pone.0007498,PMC2759292,19834602,CC BY,"BACKGROUND: Viruses interact with and exploit the host cellular machinery for their multiplication and propagation. The MEK/ERK signaling pathway positively regulates replication of many RNA viruses. However, whether and how this signaling pathway affects hepatitis C virus (HCV) replication and production is not well understood. METHODS AND RESULTS: In this study, we took advantage of two well-characterized MEK/ERK inhibitors and MEK/ERK dominant negative mutants and investigated the roles of the MEK/ERK signaling pathway in HCV gene expression and replication. We showed that inhibition of MEK/ERK signaling enhanced HCV gene expression, plus- and minus-strand RNA synthesis, and virus production. In addition, we showed that this enhancement was independent of interferon-α (IFN-α) antiviral activity and did not require prior activation of the MEK/ERK signaling pathway. Furthermore, we showed that only MEK and ERK-2 but not ERK-1 was involved in HCV replication, likely through regulation of HCV RNA translation. CONCLUSIONS: Taken together, these results demonstrate a negative regulatory role of the MEK/ERK signaling pathway in HCV replication and suggest a potential risk in targeting this signaling pathway to treat and prevent neoplastic transformation of HCV-infected liver cells.",2009 Oct 16,"['Ndjomou, Jean', 'Park, In-woo', 'Liu, Ying', 'Mayo, Lindsey D.', 'He, Johnny J.']",PLoS One,,,True
4ea207323d2fedf5b4f5a4cbb8fd1acd100df8a8,PMC,Mutagenesis of the fusion peptide-like domain of hepatitis C virus E1 glycoprotein: involvement in cell fusion and virus entry,http://dx.doi.org/10.1186/1423-0127-16-89,PMC2759930,19778418,CC BY,"BACKGROUND: Envelope (E) glycoprotein E2 of the hepatitis C virus (HCV) mediates binding of the virus to target cell receptors. Nevertheless, the precise role of E1 in viral entry remains elusive. METHODS: To understand the involvement of the fusion peptide-like domain positioned at residues 264 to 290 within envelope glycoprotein E1 in HCV infection, mutants with Ala and Asn substitutions for residues conserved between HCV and E proteins of flaviviruses or the fusion proteins of paramyxoviruses were constructed by site-directed mutagenesis and their effects on membrane fusion and viral infectivity were examined. RESULTS: None of these mutations affected the synthesis or cell surface expression of envelope proteins, nor did they alter the formation of a non-covalent E1-E2 heterodimer or E2 binding to the large extracellular loop of CD81. The Cys residues located at positions 272 and 281 were unlikely involved in intra- or intermolecular disulfide bond formation. With the exception of the G267A mutant, which showed increased cell fusion, other mutants displayed reduced or marginally inhibited cell fusion capacities compared to the wild-type (WT) E1E2. The G267A mutant was also an exception in human immunodeficiency virus type 1 (HIV-1)/HCV E1E2 pseudotyping analyses, in that it showed higher one-cycle infectivity; all other mutants exhibited greatly or partially reduced viral entry versus the WT pseudotype. All but the G278A and D279N mutants showed a WT-like profile of E1E2 incorporation into HIV-1 particles. Since C272A, C281A, G282A, and G288A pseudotypes bound to Huh7 cells as effectively as did the WT pseudotype, the reduced infectivity of these pseudotypes was due to their ability to inhibit cell fusion. CONCLUSION: Our results indicate that specific residues, but not the structure, of this fusion peptide-like domain are required for mediating cell fusion and viral entry.",2009 Sep 24,"['Li, Hsiao-Fen', 'Huang, Chia-Hsuan', 'Ai, Li-Shuang', 'Chuang, Chin-Kai', 'Chen, Steve SL']",J Biomed Sci,,,True
80a735987ea3897dc5e33a859e1a80310babb2da,PMC,Detection of HIV-1 RNA/DNA and CD4 mRNA in feces and urine from chronic HIV-1 infected subjects with and without anti-retroviral therapy,http://dx.doi.org/10.1186/1742-6405-6-20,PMC2761414,19799780,CC BY,"HIV-1 infects gut associated lymphoid tissues (GALT) very early after transmission by multiple routes. The infected GALT consequently serves as the major reservoir for HIV-1 infection and could constantly shed HIV-1 and CD4(+ )T cells into the intestinal lumen. To examine this hypothesis, we monitored HIV-1 RNA/DNA and CD4 mRNA in fecal samples of chronically infected subjects with and without antiretroviral therapy (ART). We compared this to levels of HIV-1 RNA/DNA in urine and blood from the same subjects. Our results show that HIV-1 DNA, RNA and CD4 mRNA were detected in 8%, 19% and 31% respectively, of feces samples from infected subjects with detectable plasma viral load, and were not detected in any of subjects on ART with undetectable plasma viral load. In urine samples, HIV-1 DNA was detected in 24% of infected subjects with detectable plasma viral load and 23% of subjects on ART with undetectable plasma viral load. Phylogenetic analysis of the envelope sequences of HIV-1 revealed distinct virus populations in concurrently collected serum, feces and urine samples from one subject. In addition, our study demonstrated for the first time the presence of CD4 mRNA in fecal specimens of HIV-1 infected subjects, which could be used to assess GALT pathogenesis in HIV-1 infection.",2009 Oct 2,"['Chakrabarti, Ayan K', 'Caruso, Lori', 'Ding, Ming', 'Shen, Chengli', 'Buchanan, William', 'Gupta, Phalguni', 'Rinaldo, Charles R', 'Chen, Yue']",AIDS Res Ther,,,True
69422fc5757c3c88a574d830594a4dc1a06337b9,PMC,Small islands and pandemic influenza: Potential benefits and limitations of travel volume reduction as a border control measure,http://dx.doi.org/10.1186/1471-2334-9-160,PMC2761921,19788751,CC BY,"BACKGROUND: Some island nations have explicit components of their influenza pandemic plans for providing travel warnings and restricting incoming travellers. But the potential value of such restrictions has not been quantified. METHODS: We developed a probabilistic model and used parameters from a published model (i.e., InfluSim) and travel data from Pacific Island Countries and Territories (PICTs). RESULTS: The results indicate that of the 17 PICTs with travel data, only six would be likely to escape a major pandemic with a viral strain of relatively low contagiousness (i.e., for R(0 )= 1.5) even when imposing very tight travel volume reductions of 99% throughout the course of the pandemic. For a more contagious viral strain (R(0 )= 2.25) only five PICTs would have a probability of over 50% to escape. The total number of travellers during the pandemic must not exceed 115 (for R(0 )= 3.0) or 380 (for R(0 )= 1.5) if a PICT aims to keep the probability of pandemic arrival below 50%. CONCLUSION: These results suggest that relatively few island nations could successfully rely on intensive travel volume restrictions alone to avoid the arrival of pandemic influenza (or subsequent waves). Therefore most island nations may need to plan for multiple additional interventions (e.g., screening and quarantine) to raise the probability of remaining pandemic free or achieving substantial delay in pandemic arrival.",2009 Sep 29,"['Eichner, Martin', 'Schwehm, Markus', 'Wilson, Nick', 'Baker, Michael G']",BMC Infect Dis,,,True
ab23c1ed37392d4e2dbbd809e62171775e75369b,PMC,Evasion by Stealth: Inefficient Immune Activation Underlies Poor T Cell Response and Severe Disease in SARS-CoV-Infected Mice,http://dx.doi.org/10.1371/journal.ppat.1000636,PMC2762542,19851468,CC BY,"Severe Acute Respiratory Syndrome caused substantial morbidity and mortality during the 2002–2003 epidemic. Many of the features of the human disease are duplicated in BALB/c mice infected with a mouse-adapted version of the virus (MA15), which develop respiratory disease with high morbidity and mortality. Here, we show that severe disease is correlated with slow kinetics of virus clearance and delayed activation and transit of respiratory dendritic cells (rDC) to the draining lymph nodes (DLN) with a consequent deficient virus-specific T cell response. All of these defects are corrected when mice are treated with liposomes containing clodronate, which deplete alveolar macrophages (AM). Inhibitory AMs are believed to prevent the development of immune responses to environmental antigens and allergic responses by interacting with lung dendritic cells and T cells. The inhibitory effects of AM can also be nullified if mice or AMs are pretreated with poly I:C, which directly activate AMs and rDCs through toll-like receptors 3 (TLR3). Further, adoptive transfer of activated but not resting bone marrow–derived dendritic cells (BMDC) protect mice from lethal MA15 infection. These results may be relevant for SARS in humans, which is also characterized by prolonged virus persistence and delayed development of a SARS-CoV-specific immune response in individuals with severe disease.",2009 Oct 23,"['Zhao, Jincun', 'Zhao, Jingxian', 'Van Rooijen, Nico', 'Perlman, Stanley']",PLoS Pathog,,,True
9721af1b88d60abbff468d841941f85a13731861,PMC,Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis,http://dx.doi.org/10.1136/thx.2008.112466,PMC2764123,19574243,CC BY,"BACKGROUND: Pseudomonas aeruginosa is the most common bacterial pathogen in patients with cystic fibrosis (CF). Current infection control guidelines aim to prevent transmission via contact and respiratory droplet routes and do not consider the possibility of airborne transmission. It was hypothesised that subjects with CF produce viable respirable bacterial aerosols with coughing. METHODS: A cross-sectional study was undertaken of 15 children and 13 adults with CF, 26 chronically infected with P aeruginosa. A cough aerosol sampling system enabled fractioning of respiratory particles of different sizes and culture of viable Gram-negative non-fermentative bacteria. Cough aerosols were collected during 5 min of voluntary coughing and during a sputum induction procedure when tolerated. Standardised quantitative culture and genotyping techniques were used. RESULTS: P aeruginosa was isolated in cough aerosols of 25 subjects (89%), 22 of whom produced sputum samples. P aeruginosa from sputum and paired cough aerosols were indistinguishable by molecular typing. In four cases the same genotype was isolated from ambient room air. Approximately 70% of viable aerosols collected during voluntary coughing were of particles ⩽3.3 μm aerodynamic diameter. P aeruginosa, Burkholderia cenocepacia, Stenotrophomonas maltophilia and Achromobacter xylosoxidans were cultivated from respiratory particles in this size range. Positive room air samples were associated with high total counts in cough aerosols (p = 0.003). The magnitude of cough aerosols was associated with higher forced expiratory volume in 1 s (r = 0.45, p = 0.02) and higher quantitative sputum culture results (r = 0.58, p = 0.008). CONCLUSION: During coughing, patients with CF produce viable aerosols of P aeruginosa and other Gram-negative bacteria of respirable size range, suggesting the potential for airborne transmission.",2009 Nov 1,"['Wainwright, C E', 'France, M W', 'O’Rourke, P', 'Anuj, S', 'Kidd, T J', 'Nissen, M D', 'Sloots, T P', 'Coulter, C', 'Ristovski, Z', 'Hargreaves, M', 'Rose, B R', 'Harbour, C', 'Bell, S C', 'Fennelly, K P']",Thorax,,,True
ffef8194e52de95fe345db7dd12fe3185d786978,PMC,Evidence of HIV-1 adaptation to host HLA alleles following chimp-to-human transmission,http://dx.doi.org/10.1186/1743-422X-6-164,PMC2765438,19818146,CC BY,"BACKGROUND: The cytotoxic T-lymphocyte immune response is important in controlling HIV-1 replication in infected humans. In this immune pathway, viral peptides within infected cells are presented to T-lymphocytes by the polymorphic human leukocyte antigens (HLA). HLA alleles exert selective pressure on the peptide regions and immune escape mutations that occur at some of the targeted sites can enable the virus to adapt to the infected host. The pattern of ongoing immune escape and reversion associated with several human HLA alleles has been studied extensively. Such mutations revert upon transmission to a host without the HLA allele because the escape mutation incurs a fitness cost. However, to-date there has been little attempt to study permanent loss of CTL epitopes due to escape mutations without an effect on fitness. RESULTS: Here, we set out to determine the extent of adaptation of HIV-1 to three well-characterized HLA alleles during the initial exposure of the virus to the human cytotoxic immune responses following transmission from chimpanzee. We generated a chimpanzee consensus sequence to approximate the virus sequence that was initially transmitted to the human host and used a method based on peptide binding affinity to HLA crystal structures to predict peptides that were potentially targeted by the HLA alleles on this sequence. Next, we used codon-based phylogenetic models to quantify the average selective pressure that acted on these regions during the period immediately following the zoonosis event, corresponding to the branch of the phylogenetic tree leading to the common ancestor of all of the HIV-1 sequences. Evidence for adaptive evolution during this period was observed at regions recognised by HLA A*6801 and A*0201, both of which are common in African populations. No evidence of adaptive evolution was observed at sites targeted by HLA-B*2705, which is a rare allele in African populations. CONCLUSION: Our results suggest that the ancestral HIV-1 virus experienced a period of positive selective pressure due to immune responses associated with HLA alleles that were common in the infected human population. We propose that this resulted in permanent escape from immune responses targeting unconstrained regions of the virus.",2009 Oct 10,"['Ngandu, Nobubelo K', 'Seoighe, Cathal', 'Scheffler, Konrad']",Virol J,,,True
9ffa106061fd815e4bb93389274819e640dfb840,PMC,"Initial psychological responses to Influenza A, H1N1 (""Swine flu"")",http://dx.doi.org/10.1186/1471-2334-9-166,PMC2765446,19807908,CC BY,"BACKGROUND: The outbreak of the pandemic flu, Influenza A H1N1 (Swine Flu) in early 2009, provided a major challenge to health services around the world. Previous pandemics have led to stockpiling of goods, the victimisation of particular population groups, and the cancellation of travel and the boycotting of particular foods (e.g. pork). We examined initial behavioural and attitudinal responses towards Influenza A, H1N1 (""Swine flu"") in the six days following the WHO pandemic alert level 5, and regional differences in these responses. METHODS: 328 respondents completed a cross-sectional Internet or paper-based questionnaire study in Malaysia (N = 180) or Europe (N = 148). Measures assessed changes in transport usage, purchase of preparatory goods for a pandemic, perceived risk groups, indicators of anxiety, assessed estimated mortality rates for seasonal flu, effectiveness of seasonal flu vaccination, and changes in pork consumption RESULTS: 26% of the respondents were 'very concerned' about being a flu victim (42% Malaysians, 5% Europeans, p < .001). 36% reported reduced public transport use (48% Malaysia, 22% Europe, p < .001), 39% flight cancellations (56% Malaysia, 17% Europe, p < .001). 8% had purchased preparatory materials (e.g. face masks: 8% Malaysia, 7% Europe), 41% Malaysia (15% Europe) intended to do so (p < .001). 63% of Europeans, 19% of Malaysians had discussed the pandemic with friends (p < .001). Groups seen as at 'high risk' of infection included the immune compromised (mentioned by 87% respondents), pig farmers (70%), elderly (57%), prostitutes/highly sexually active (53%), and the homeless (53%). In data collected only in Europe, 64% greatly underestimated the mortality rates of seasonal flu, 26% believed seasonal flu vaccination gave protection against swine flu. 7% had reduced/stopped eating pork. 3% had purchased anti-viral drugs for use at home, while 32% intended to do so if the pandemic worsened. CONCLUSION: Initial responses to Influenza A show large regional differences in anxiety, with Malaysians more anxious and more likely to reduce travel and to buy masks and food. Discussions with family and friends may reinforce existing anxiety levels. Particular groups (homosexuals, prostitutes, the homeless) are perceived as at greater risk, potentially leading to increased prejudice during a pandemic. Europeans underestimated mortality of seasonal flu, and require more information about the protection given by seasonal flu inoculation.",2009 Oct 6,"['Goodwin, Robin', 'Haque, Shamsul', 'Neto, Felix', 'Myers, Lynn B']",BMC Infect Dis,,,True
74813899dfd7ad7de15228fd014c735c3410d9d9,PMC,A Neutralizing Human Monoclonal Antibody Protects against Lethal Disease in a New Ferret Model of Acute Nipah Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1000642,PMC2765826,19888339,CC0,"Nipah virus is a broadly tropic and highly pathogenic zoonotic paramyxovirus in the genus Henipavirus whose natural reservoirs are several species of Pteropus fruit bats. Nipah virus has repeatedly caused outbreaks over the past decade associated with a severe and often fatal disease in humans and animals. Here, a new ferret model of Nipah virus pathogenesis is described where both respiratory and neurological disease are present in infected animals. Severe disease occurs with viral doses as low as 500 TCID(50) within 6 to 10 days following infection. The underlying pathology seen in the ferret closely resembles that seen in Nipah virus infected humans, characterized as a widespread multisystemic vasculitis, with virus replicating in highly vascular tissues including lung, spleen and brain, with recoverable virus from a variety of tissues. Using this ferret model a cross-reactive neutralizing human monoclonal antibody, m102.4, targeting the henipavirus G glycoprotein was evaluated in vivo as a potential therapeutic agent. All ferrets that received m102.4 ten hours following a high dose oral-nasal Nipah virus challenge were protected from disease while all controls died. This study is the first successful post-exposure passive antibody therapy for Nipah virus using a human monoclonal antibody.",2009 Oct 30,"['Bossart, Katharine N.', 'Zhu, Zhongyu', 'Middleton, Deborah', 'Klippel, Jessica', 'Crameri, Gary', 'Bingham, John', 'McEachern, Jennifer A.', 'Green, Diane', 'Hancock, Timothy J.', 'Chan, Yee-Peng', 'Hickey, Andrew C.', 'Dimitrov, Dimiter S.', 'Wang, Lin-Fa', 'Broder, Christopher C.']",PLoS Pathog,,,True
a6d3a67189b0d60da49032d2192a681dc06f5459,PMC,The influenza A(H1N1) epidemic in Mexico. Lessons learned,http://dx.doi.org/10.1186/1478-4505-7-21,PMC2765941,19785747,CC BY,"Several influenza pandemics have taken place throughout history and it was assumed that the pandemic would emerge from a new human virus resulting from the adaptation of an avian virus strain. Mexico, since 2003 had developed a National Preparedness and Response Plan for an Influenza Pandemic focused in risk communication, health promotion, healthcare, epidemiological surveillance, strategic stockpile, research and development. This plan was challenged on April 2009, when a new influenza A(H1N1) strain of swine origen was detected in Mexico. The situation faced, the decisions and actions taken, allowed to control the first epidemic wave in the country. This document describes the critical moments faced and explicitly point out the lessons learned focused on the decided support by the government, the National Pandemic Influenza Plan, the coordination among all the government levels, the presence and solidarity of international organizations with timely and daily information, diagnosis and the positive effect on the population following the preventive hygienic measures recommended by the health authorities. The international community will be able to use the Mexican experience in the interest of global health.",2009 Sep 28,"['Córdova-Villalobos, José A', 'Sarti, Elsa', 'Arzoz-Padrés, Jacqueline', 'Manuell-Lee, Gabriel', 'Méndez, Josefina Romero', 'Kuri-Morales, Pablo']",Health Res Policy Syst,,,True
c851e8a17951dc6f713c2a832e6a516f72154a79,PMC,A Protective Role for ELR+ Chemokines during Acute Viral Encephalomyelitis,http://dx.doi.org/10.1371/journal.ppat.1000648,PMC2766051,19893623,CC BY,"The functional role of ELR-positive CXC chemokines in host defense during acute viral-induced encephalomyelitis was determined. Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of mice resulted in the rapid mobilization of PMNs expressing the chemokine receptor CXCR2 into the blood. Migration of PMNs to the CNS coincided with increased expression of transcripts specific for the CXCR2 ELR-positive chemokine ligands CXCL1, CXCL2, and CXCL5 within the brain. Treatment of JHMV-infected mice with anti-CXCR2 blocking antibody reduced PMN trafficking into the CNS by >95%, dampened MMP-9 activity, and abrogated blood-brain-barrier (BBB) breakdown. Correspondingly, CXCR2 neutralization resulted in diminished infiltration of virus-specific T cells, an inability to control viral replication within the brain, and 100% mortality. Blocking CXCR2 signaling did not impair the generation of virus-specific T cells, indicating that CXCR2 is not required to tailor anti-JHMV T cell responses. Evaluation of mice in which CXCR2 is genetically silenced (CXCR2−/− mice) confirmed that PMNs neither expressed CXCR2 nor migrated in response to ligands CXCL1, CXCL2, or CXCL5 in an in vitro chemotaxis assay. Moreover, JHMV infection of CXCR2−/− mice resulted in an approximate 60% reduction of PMN migration into the CNS, yet these mice survived infection and controlled viral replication within the brain. Treatment of JHMV-infected CXCR2−/− mice with anti-CXCR2 antibody did not modulate PMN migration nor alter viral clearance or mortality, indicating the existence of compensatory mechanisms that facilitate sufficient migration of PMNs into the CNS in the absence of CXCR2. Collectively, these findings highlight a previously unappreciated role for ELR-positive chemokines in enhancing host defense during acute viral infections of the CNS.",2009 Nov 6,"['Hosking, Martin P.', 'Liu, Liping', 'Ransohoff, Richard M.', 'Lane, Thomas E.']",PLoS Pathog,,,True
e15d2db8625e8442fd8c535564897d49258d1635,PMC,A Protective Role for ELR+ Chemokines during Acute Viral Encephalomyelitis,http://dx.doi.org/10.1371/journal.ppat.1000648,PMC2766051,19893623,CC BY,"The functional role of ELR-positive CXC chemokines in host defense during acute viral-induced encephalomyelitis was determined. Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of mice resulted in the rapid mobilization of PMNs expressing the chemokine receptor CXCR2 into the blood. Migration of PMNs to the CNS coincided with increased expression of transcripts specific for the CXCR2 ELR-positive chemokine ligands CXCL1, CXCL2, and CXCL5 within the brain. Treatment of JHMV-infected mice with anti-CXCR2 blocking antibody reduced PMN trafficking into the CNS by >95%, dampened MMP-9 activity, and abrogated blood-brain-barrier (BBB) breakdown. Correspondingly, CXCR2 neutralization resulted in diminished infiltration of virus-specific T cells, an inability to control viral replication within the brain, and 100% mortality. Blocking CXCR2 signaling did not impair the generation of virus-specific T cells, indicating that CXCR2 is not required to tailor anti-JHMV T cell responses. Evaluation of mice in which CXCR2 is genetically silenced (CXCR2−/− mice) confirmed that PMNs neither expressed CXCR2 nor migrated in response to ligands CXCL1, CXCL2, or CXCL5 in an in vitro chemotaxis assay. Moreover, JHMV infection of CXCR2−/− mice resulted in an approximate 60% reduction of PMN migration into the CNS, yet these mice survived infection and controlled viral replication within the brain. Treatment of JHMV-infected CXCR2−/− mice with anti-CXCR2 antibody did not modulate PMN migration nor alter viral clearance or mortality, indicating the existence of compensatory mechanisms that facilitate sufficient migration of PMNs into the CNS in the absence of CXCR2. Collectively, these findings highlight a previously unappreciated role for ELR-positive chemokines in enhancing host defense during acute viral infections of the CNS.",2009 Nov 6,"['Hosking, Martin P.', 'Liu, Liping', 'Ransohoff, Richard M.', 'Lane, Thomas E.']",PLoS Pathog,,,False
dd6da0893e5676f45747ab0ef6a4fa98007cc113,PMC,A Protective Role for ELR+ Chemokines during Acute Viral Encephalomyelitis,http://dx.doi.org/10.1371/journal.ppat.1000648,PMC2766051,19893623,CC BY,"The functional role of ELR-positive CXC chemokines in host defense during acute viral-induced encephalomyelitis was determined. Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of mice resulted in the rapid mobilization of PMNs expressing the chemokine receptor CXCR2 into the blood. Migration of PMNs to the CNS coincided with increased expression of transcripts specific for the CXCR2 ELR-positive chemokine ligands CXCL1, CXCL2, and CXCL5 within the brain. Treatment of JHMV-infected mice with anti-CXCR2 blocking antibody reduced PMN trafficking into the CNS by >95%, dampened MMP-9 activity, and abrogated blood-brain-barrier (BBB) breakdown. Correspondingly, CXCR2 neutralization resulted in diminished infiltration of virus-specific T cells, an inability to control viral replication within the brain, and 100% mortality. Blocking CXCR2 signaling did not impair the generation of virus-specific T cells, indicating that CXCR2 is not required to tailor anti-JHMV T cell responses. Evaluation of mice in which CXCR2 is genetically silenced (CXCR2−/− mice) confirmed that PMNs neither expressed CXCR2 nor migrated in response to ligands CXCL1, CXCL2, or CXCL5 in an in vitro chemotaxis assay. Moreover, JHMV infection of CXCR2−/− mice resulted in an approximate 60% reduction of PMN migration into the CNS, yet these mice survived infection and controlled viral replication within the brain. Treatment of JHMV-infected CXCR2−/− mice with anti-CXCR2 antibody did not modulate PMN migration nor alter viral clearance or mortality, indicating the existence of compensatory mechanisms that facilitate sufficient migration of PMNs into the CNS in the absence of CXCR2. Collectively, these findings highlight a previously unappreciated role for ELR-positive chemokines in enhancing host defense during acute viral infections of the CNS.",2009 Nov 6,"['Hosking, Martin P.', 'Liu, Liping', 'Ransohoff, Richard M.', 'Lane, Thomas E.']",PLoS Pathog,,,False
2d260d046e4a6ba91ec7c811f0362340f4d4a3d4,PMC,A Protective Role for ELR+ Chemokines during Acute Viral Encephalomyelitis,http://dx.doi.org/10.1371/journal.ppat.1000648,PMC2766051,19893623,CC BY,"The functional role of ELR-positive CXC chemokines in host defense during acute viral-induced encephalomyelitis was determined. Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of mice resulted in the rapid mobilization of PMNs expressing the chemokine receptor CXCR2 into the blood. Migration of PMNs to the CNS coincided with increased expression of transcripts specific for the CXCR2 ELR-positive chemokine ligands CXCL1, CXCL2, and CXCL5 within the brain. Treatment of JHMV-infected mice with anti-CXCR2 blocking antibody reduced PMN trafficking into the CNS by >95%, dampened MMP-9 activity, and abrogated blood-brain-barrier (BBB) breakdown. Correspondingly, CXCR2 neutralization resulted in diminished infiltration of virus-specific T cells, an inability to control viral replication within the brain, and 100% mortality. Blocking CXCR2 signaling did not impair the generation of virus-specific T cells, indicating that CXCR2 is not required to tailor anti-JHMV T cell responses. Evaluation of mice in which CXCR2 is genetically silenced (CXCR2−/− mice) confirmed that PMNs neither expressed CXCR2 nor migrated in response to ligands CXCL1, CXCL2, or CXCL5 in an in vitro chemotaxis assay. Moreover, JHMV infection of CXCR2−/− mice resulted in an approximate 60% reduction of PMN migration into the CNS, yet these mice survived infection and controlled viral replication within the brain. Treatment of JHMV-infected CXCR2−/− mice with anti-CXCR2 antibody did not modulate PMN migration nor alter viral clearance or mortality, indicating the existence of compensatory mechanisms that facilitate sufficient migration of PMNs into the CNS in the absence of CXCR2. Collectively, these findings highlight a previously unappreciated role for ELR-positive chemokines in enhancing host defense during acute viral infections of the CNS.",2009 Nov 6,"['Hosking, Martin P.', 'Liu, Liping', 'Ransohoff, Richard M.', 'Lane, Thomas E.']",PLoS Pathog,,,False
a7eabb9cc3d54246f76429da3a972e819d075a1d,PMC,A Protective Role for ELR+ Chemokines during Acute Viral Encephalomyelitis,http://dx.doi.org/10.1371/journal.ppat.1000648,PMC2766051,19893623,CC BY,"The functional role of ELR-positive CXC chemokines in host defense during acute viral-induced encephalomyelitis was determined. Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of mice resulted in the rapid mobilization of PMNs expressing the chemokine receptor CXCR2 into the blood. Migration of PMNs to the CNS coincided with increased expression of transcripts specific for the CXCR2 ELR-positive chemokine ligands CXCL1, CXCL2, and CXCL5 within the brain. Treatment of JHMV-infected mice with anti-CXCR2 blocking antibody reduced PMN trafficking into the CNS by >95%, dampened MMP-9 activity, and abrogated blood-brain-barrier (BBB) breakdown. Correspondingly, CXCR2 neutralization resulted in diminished infiltration of virus-specific T cells, an inability to control viral replication within the brain, and 100% mortality. Blocking CXCR2 signaling did not impair the generation of virus-specific T cells, indicating that CXCR2 is not required to tailor anti-JHMV T cell responses. Evaluation of mice in which CXCR2 is genetically silenced (CXCR2−/− mice) confirmed that PMNs neither expressed CXCR2 nor migrated in response to ligands CXCL1, CXCL2, or CXCL5 in an in vitro chemotaxis assay. Moreover, JHMV infection of CXCR2−/− mice resulted in an approximate 60% reduction of PMN migration into the CNS, yet these mice survived infection and controlled viral replication within the brain. Treatment of JHMV-infected CXCR2−/− mice with anti-CXCR2 antibody did not modulate PMN migration nor alter viral clearance or mortality, indicating the existence of compensatory mechanisms that facilitate sufficient migration of PMNs into the CNS in the absence of CXCR2. Collectively, these findings highlight a previously unappreciated role for ELR-positive chemokines in enhancing host defense during acute viral infections of the CNS.",2009 Nov 6,"['Hosking, Martin P.', 'Liu, Liping', 'Ransohoff, Richard M.', 'Lane, Thomas E.']",PLoS Pathog,,,False
75aa45fec583443ad040672ab48b2c90825a94bb,PMC,New journal selection for quantitative survey of infectious disease research: application for Asian trend analysis,http://dx.doi.org/10.1186/1471-2288-9-67,PMC2766390,19804650,CC BY,"BACKGROUND: Quantitative survey of research articles, as an application of bibliometrics, is an effective tool for grasping overall trends in various medical research fields. This type of survey has been also applied to infectious disease research; however, previous studies were insufficient as they underestimated articles published in non-English or regional journals. METHODS: Using a combination of Scopus™ and PubMed, the databases of scientific literature, and English and non-English keywords directly linked to infectious disease control, we identified international and regional infectious disease journals. In order to ascertain whether the newly selected journals were appropriate to survey a wide range of research articles, we compared the number of original articles and reviews registered in the selected journals to those in the 'Infectious Disease Category' of the Science Citation Index Expanded™ (SCI Infectious Disease Category) during 1998-2006. Subsequently, we applied the newly selected journals to survey the number of original articles and reviews originating from 11 Asian countries during the same period. RESULTS: One hundred journals, written in English or 7 non-English languages, were newly selected as infectious disease journals. The journals published 14,156 original articles and reviews of Asian origin and 118,158 throughout the world, more than those registered in the SCI Infectious Disease Category (4,621 of Asian origin and 66,518 of the world in the category). In Asian trend analysis of the 100 journals, Japan had the highest percentage of original articles and reviews in the area, and no noticeable increase in articles was revealed during the study period. China, India and Taiwan had relatively large numbers and a high increase rate of original articles among Asian countries. When adjusting the publication of original articles according to the country population and the gross domestic product (GDP), Singapore and Taiwan were the most productive. CONCLUSION: A survey of 100 selected journals is more sensitive than the SCI Infectious Disease Category from the viewpoint of avoiding underestimating the number of infectious disease research articles of Asian origin. The survey method is applicable to grasp global trends in disease research, although the method may require further development.",2009 Oct 6,"['Takahashi-Omoe, Hiromi', 'Omoe, Katsuhiko', 'Okabe, Nobuhiko']",BMC Med Res Methodol,,,True
c248b6eb16165b2b06281401eaeb99df0ba7f211,PMC,Barriers and supports to implementation of MDI/spacer use in nine Canadian pediatric emergency departments: a qualitative study,http://dx.doi.org/10.1186/1748-5908-4-65,PMC2766417,19828086,CC BY,"BACKGROUND: Despite recent research supporting the use of metered dose inhalers with spacer devices (MDI/spacers) in pediatric emergency departments (PEDs) for acute exacerbations of asthma, uptake of this practice has been slow. The objectives of this study were to determine the barriers and supports to implementing MDI/spacer research and to identify factors associated with early and late adoption of MDI/spacers in Canadian PEDs. METHODS: Using a comparative case study design, we classified nine tertiary care pediatric hospital PEDs based on their stage of implementation. Data were collected using focus group interviews with physicians, registered nurses (RNs), and respiratory therapists (RTs), and individual interviews with both patient care and medical directors at each site. Initial coding was based on the Ottawa Model of Research Use (OMRU) categories of elements known to influence the uptake of innovations. RESULTS: One hundred and fifty healthcare professionals from nine different healthcare institutions participated in this study. Lack of leadership in the form of a research champion, a lack of consensus about the benefits of MDI/spacers among staff, perceived resistance from patients/parents, and perceived increased cost and workload associated with MDI/spacer use were the most prevalent barriers to the adoption of the MDI/spacer. Common strategies used by early-adopting sites included the active participation of all professional groups in the adoption process in addition to a well-planned and executed educational component for staff, patients, and families. Early adopter sites were also more likely to have the MDI/spacer included in a clinical protocol/pathway. CONCLUSION: Potential barriers and supports to implementation have been identified that will help EDs adopt MDI/spacer use. Future interventions intended to increase MDI/spacer use in PEDs will need to be sensitive to the barriers identified in this study.",2009 Oct 13,"['Scott, Shannon D', 'Osmond, Martin H', ""O'Leary, Kathy A"", 'Graham, Ian D', 'Grimshaw, Jeremy', 'Klassen, Terry', None]",Implement Sci,,,True
f8710043513b5790e20921e8a36d1cc94b402701,PMC,Analysis of virion associated host proteins in vesicular stomatitis virus using a proteomics approach,http://dx.doi.org/10.1186/1743-422X-6-166,PMC2770056,19821998,CC BY,"BACKGROUND: Vesicular stomatitis virus (VSV) is the prototypic rhabdovirus and the best studied member of the order Mononegavirales. There is now compelling evidence that enveloped virions released from infected cells carry numerous host (cellular) proteins some of which may play an important role in viral replication. Although several cellular proteins have been previously shown to be incorporated into VSV virions, no systematic study has been done to reveal the host protein composition for virions of VSV or any other member of Mononegavirales. RESULTS: Here we used a proteomics approach to identify cellular proteins within purified VSV virions, thereby creating a ""snapshot"" of one stage of virus/host interaction that can guide future experiments aimed at understanding molecular mechanisms of virus-cell interactions. Highly purified preparations of VSV virions from three different cell lines of human, mouse and hamster origin were analyzed for the presence of cellular proteins using mass spectrometry. We have successfully confirmed the presence of several previously-identified cellular proteins within VSV virions and identified a number of additional proteins likely to also be present within the virions. In total, sixty-four cellular proteins were identified, of which nine were found in multiple preparations. A combination of immunoblotting and proteinase K protection assay was used to verify the presence of several of these proteins (integrin β1, heat shock protein 90 kDa, heat shock cognate 71 kDa protein, annexin 2, elongation factor 1a) within the virions. CONCLUSION: This is, to our knowledge, the first systematic study of the host protein composition for virions of VSV or any other member of the order Mononegavirales. Future experiments are needed to determine which of the identified proteins have an interaction with VSV and whether these interactions are beneficial, neutral or antiviral with respect to VSV replication. Identification of host proteins-virus interactions beneficial for virus would be particularly exciting as they can provide new ways to combat viral infections via control of host components.",2009 Oct 12,"['Moerdyk-Schauwecker, Megan', 'Hwang, Sun-Il', 'Grdzelishvili, Valery Z']",Virol J,,,True
600e8fba699669f496224f1ab80caa3df030a77a,PMC,Using Dynamic Stochastic Modelling to Estimate Population Risk Factors in Infectious Disease: The Example of FIV in 15 Cat Populations,http://dx.doi.org/10.1371/journal.pone.0007377,PMC2770169,19888418,CC BY,"BACKGROUND: In natural cat populations, Feline Immunodeficiency Virus (FIV) is transmitted through bites between individuals. Factors such as the density of cats within the population or the sex-ratio can have potentially strong effects on the frequency of fight between individuals and hence appear as important population risk factors for FIV. METHODOLOGY/PRINCIPAL FINDINGS: To study such population risk factors, we present data on FIV prevalence in 15 cat populations in northeastern France. We investigate five key social factors of cat populations; the density of cats, the sex-ratio, the number of males and the mean age of males and females within the population. We overcome the problem of dependence in the infective status data using sexually-structured dynamic stochastic models. Only the age of males and females had an effect (p = 0.043 and p = 0.02, respectively) on the male-to-female transmission rate. Due to multiple tests, it is even likely that these effects are, in reality, not significant. Finally we show that, in our study area, the data can be explained by a very simple model that does not invoke any risk factor. CONCLUSION: Our conclusion is that, in host-parasite systems in general, fluctuations due to stochasticity in the transmission process are naturally very large and may alone explain a larger part of the variability in observed disease prevalence between populations than previously expected. Finally, we determined confidence intervals for the simple model parameters that can be used to further aid in management of the disease.",2009 Oct 16,"['Fouchet, David', 'Leblanc, Guillaume', 'Sauvage, Frank', 'Guiserix, Micheline', 'Poulet, Hervé', 'Pontier, Dominique']",PLoS One,,,True
f07550405043e5c3820e2c85a0b8003b64e8e163,PMC,Cleavage of the SARS Coronavirus Spike Glycoprotein by Airway Proteases Enhances Virus Entry into Human Bronchial Epithelial Cells In Vitro,http://dx.doi.org/10.1371/journal.pone.0007870,PMC2773421,19924243,CC BY,"BACKGROUND: Entry of enveloped viruses into host cells requires the activation of viral envelope glycoproteins through cleavage by either intracellular or extracellular proteases. In order to gain insight into the molecular basis of protease cleavage and its impact on the efficiency of viral entry, we investigated the susceptibility of a recombinant native full-length S-protein trimer (triSpike) of the severe acute respiratory syndrome coronavirus (SARS-CoV) to cleavage by various airway proteases. METHODOLOGY/PRINCIPAL FINDINGS: Purified triSpike proteins were readily cleaved in vitro by three different airway proteases: trypsin, plasmin and TMPRSS11a. High Performance Liquid Chromatography (HPLC) and amino acid sequencing analyses identified two arginine residues (R667 and R797) as potential protease cleavage site(s). The effect of protease-dependent enhancement of SARS-CoV infection was demonstrated with ACE2 expressing human bronchial epithelial cells 16HBE. Airway proteases regulate the infectivity of SARS-CoV in a fashion dependent on previous receptor binding. The role of arginine residues was further shown with mutant constructs (R667A, R797A or R797AR667A). Mutation of R667 or R797 did not affect the expression of S-protein but resulted in a differential efficacy of pseudotyping into SARS-CoVpp. The R667A SARS-CoVpp mutant exhibited a lack of virus entry enhancement following protease treatment. CONCLUSIONS/SIGNIFICANCE: These results suggest that SARS S-protein is susceptible to airway protease cleavage and, furthermore, that protease mediated enhancement of virus entry depends on specific conformation of SARS S-protein upon ACE2 binding. These data have direct implications for the cell entry mechanism of SARS-CoV along the respiratory system and, furthermore expand the possibility of identifying potential therapeutic agents against SARS-CoV.",2009 Nov 17,"['Kam, Yiu-Wing', 'Okumura, Yuushi', 'Kido, Hiroshi', 'Ng, Lisa F. P.', 'Bruzzone, Roberto', 'Altmeyer, Ralf']",PLoS One,,,True
4d0d82be6ba94422e252ff243a2cd89d13ea736a,PMC,MicroRNome Analysis Unravels the Molecular Basis of SARS Infection in Bronchoalveolar Stem Cells,http://dx.doi.org/10.1371/journal.pone.0007837,PMC2773932,19915717,CC BY,"Severe acute respiratory syndrome (SARS), caused by the coronavirus SARS-CoV, is an acute infectious disease with significant mortality. A typical clinical feature associated with SARS is pulmonary fibrosis and associated lung failure. In the aftermath of the SARS epidemic, although significant progress towards understanding the underlying molecular mechanism of the infection has been made, a large gap still remains in our knowledge regarding how SARS-CoV interacts with the host cell at the onset of infection. The rapidly changing viral genome adds another variable to this equation. We have focused on a novel concept of microRNA (miRNA)–mediated host–virus interactions in bronchoalveolar stem cells (BASCs) at the onset of infection by correlating the “BASC–microRNome” with their targets within BASCs and viral genome. This work encompasses miRNA array data analysis, target prediction, and miRNA–mRNA enrichment analysis and develops a complex interaction map among disease-related factors, miRNAs, and BASCs in SARS pathway, which will provide some clues for diagnostic markers to view an overall interplay leading to disease progression. Our observation reveals the BASCs (Sca-1+ CD34+ CD45- Pecam-), a subset of Oct-4+ ACE2+ epithelial colony cells at the broncho-alveolar duct junction, to be the prime target cells of SARS-CoV infection. Upregulated BASC miRNAs-17*, -574-5p, and -214 are co-opted by SARS-CoV to suppress its own replication and evade immune elimination until successful transmission takes place. Viral Nucleocapsid and Spike protein targets seem to co-opt downregulated miR-223 and miR-98 respectively within BASCs to control the various stages of BASC differentiation, activation of inflammatory chemokines, and downregulation of ACE2. All these effectively accounts for a successful viral transmission and replication within BASCs causing continued deterioration of lung tissues and apparent loss of capacity for lung repair. Overall, this investigation reveals another mode of exploitation of cellular miRNA machinery by virus to their own advantage.",2009 Nov 13,"['Mallick, Bibekanand', 'Ghosh, Zhumur', 'Chakrabarti, Jayprokas']",PLoS One,,,True
6efde6b65a96f7b14d75d637f5dd77f8e6e1c51c,PMC,Taipei's Use of a Multi-Channel Mass Risk Communication Program to Rapidly Reverse an Epidemic of Highly Communicable Disease,http://dx.doi.org/10.1371/journal.pone.0007962,PMC2776508,19956722,CC BY,"BACKGROUND: In September 2007, an outbreak of acute hemorrhagic conjunctivitis (AHC) occurred in Keelung City and spread to Taipei City. In response to the epidemic, a new crisis management program was implemented and tested in Taipei. METHODOLOGY AND PRINCIPAL FINDINGS: Having noticed that transmission surged on weekends during the Keelung epidemic, Taipei City launched a multi-channel mass risk communications program that included short message service (SMS) messages sent directly to approximately 2.2 million Taipei residents on Friday, October 12th, 2007. The public was told to keep symptomatic students from schools and was provided guidelines for preventing the spread of the disease at home. Epidemiological characteristics of Taipei's outbreak were analyzed from 461 sampled AHC cases. Median time from exposure to onset of the disease was 1 day. This was significantly shorter for cases occurring in family clusters than in class clusters (mean±SD: 2.6±3.2 vs. 4.39±4.82 days, p = 0.03), as well as for cases occurring in larger family clusters as opposed to smaller ones (1.2±1.7 days vs. 3.9±4.0 days, p<0.01). Taipei's program had a significant impact on patient compliance. Home confinement of symptomatic children increased from 10% to 60% (p<0.05) and helped curb the spread of AHC. Taipei experienced a rapid decrease in AHC cases between the Friday of the SMS announcement and the following Monday, October 15, (0.70% vs. 0.36%). By October 26, AHC cases reduced to 0.01%. The success of this risk communication program in Taipei (as compared to Keelung) is further reflected through rapid improvements in three epidemic indicators: (1) significantly lower crude attack rates (1.95% vs. 14.92%, p<0.001), (2) a short epidemic period of AHC (13 vs. 34 days), and (3) a quick drop in risk level (1∼2 weeks) in Taipei districts that border Keelung (the original domestic epicenter). CONCLUSIONS AND SIGNIFICANCE: The timely launch of this systematic, communication-based intervention proved effective at preventing a dangerous spike in AHC and was able to bring this high-risk disease under control. We recommend that public health officials incorporate similar methods into existing guidelines for preventing pandemic influenza and other emerging infectious diseases.",2009 Nov 23,"['Yen, Muh-Yong', 'Wu, Tsung-Shu Joseph', 'Chiu, Allen Wen-Hsiang', 'Wong, Wing-Wai', 'Wang, Po-En', 'Chan, Ta-Chien', 'King, Chwan-Chuen']",PLoS One,,,True
095bdb615ea39929bf971754be5f9250d327cfb5,PMC,Taipei's Use of a Multi-Channel Mass Risk Communication Program to Rapidly Reverse an Epidemic of Highly Communicable Disease,http://dx.doi.org/10.1371/journal.pone.0007962,PMC2776508,19956722,CC BY,"BACKGROUND: In September 2007, an outbreak of acute hemorrhagic conjunctivitis (AHC) occurred in Keelung City and spread to Taipei City. In response to the epidemic, a new crisis management program was implemented and tested in Taipei. METHODOLOGY AND PRINCIPAL FINDINGS: Having noticed that transmission surged on weekends during the Keelung epidemic, Taipei City launched a multi-channel mass risk communications program that included short message service (SMS) messages sent directly to approximately 2.2 million Taipei residents on Friday, October 12th, 2007. The public was told to keep symptomatic students from schools and was provided guidelines for preventing the spread of the disease at home. Epidemiological characteristics of Taipei's outbreak were analyzed from 461 sampled AHC cases. Median time from exposure to onset of the disease was 1 day. This was significantly shorter for cases occurring in family clusters than in class clusters (mean±SD: 2.6±3.2 vs. 4.39±4.82 days, p = 0.03), as well as for cases occurring in larger family clusters as opposed to smaller ones (1.2±1.7 days vs. 3.9±4.0 days, p<0.01). Taipei's program had a significant impact on patient compliance. Home confinement of symptomatic children increased from 10% to 60% (p<0.05) and helped curb the spread of AHC. Taipei experienced a rapid decrease in AHC cases between the Friday of the SMS announcement and the following Monday, October 15, (0.70% vs. 0.36%). By October 26, AHC cases reduced to 0.01%. The success of this risk communication program in Taipei (as compared to Keelung) is further reflected through rapid improvements in three epidemic indicators: (1) significantly lower crude attack rates (1.95% vs. 14.92%, p<0.001), (2) a short epidemic period of AHC (13 vs. 34 days), and (3) a quick drop in risk level (1∼2 weeks) in Taipei districts that border Keelung (the original domestic epicenter). CONCLUSIONS AND SIGNIFICANCE: The timely launch of this systematic, communication-based intervention proved effective at preventing a dangerous spike in AHC and was able to bring this high-risk disease under control. We recommend that public health officials incorporate similar methods into existing guidelines for preventing pandemic influenza and other emerging infectious diseases.",2009 Nov 23,"['Yen, Muh-Yong', 'Wu, Tsung-Shu Joseph', 'Chiu, Allen Wen-Hsiang', 'Wong, Wing-Wai', 'Wang, Po-En', 'Chan, Ta-Chien', 'King, Chwan-Chuen']",PLoS One,,,False
6507acff69dc9963ee7fdffc4a7f4edae0b5f609,PMC,Experimental infection in calves with a specific subtype of verocytotoxin-producing Escherichia coli O157:H7 of bovine origin,http://dx.doi.org/10.1186/1751-0147-51-43,PMC2776595,19878595,CC BY,"BACKGROUND: In Sweden, a particular subtype of verocytotoxin-producing Escherichia coli (VTEC) O157:H7, originally defined as being of phage type 4, and carrying two vtx(2 )genes, has been found to cause the majority of reported human infections during the past 15 years, including both sporadic cases and outbreaks. One plausible explanation for this could be that this particular subtype is better adapted to colonise cattle, and thereby may be excreted in greater concentrations and for longer periods than other VTEC O157:H7 subtypes. METHODS: In an experimental study, 4 calves were inoculated with 10(9 )colony forming units (cfu) of strain CCUG 53931, representative of the subtype VTEC O157:H7 (PT4;vtx(2);vtx(2c)). Two un-inoculated calves were co-housed with the inoculated calves. Initially, the VTEC O157:H7 strain had been isolated from a dairy herd with naturally occurring infection and the farm had previously also been linked to human infection with the same strain. Faecal samples were collected over up to a 2-month period and analysed for VTEC O157 by immuno-magnetic separation (IMS), and IMS positive samples were further analysed by direct plating to elucidate the shedding pattern. Samples were also collected from the pharynx. RESULTS: All inoculated calves proved culture-positive in faeces within 24 hours after inoculation and the un-inoculated calves similarly on days 1 and 3 post-inoculation. One calf was persistently culture-positive for 43 days; in the remainder, the VTEC O157:H7 count in faeces decreased over the first 2 weeks. All pharyngeal samples were culture-negative for VTEC O157:H7. CONCLUSION: This study contributes with information concerning the dynamics of a specific subtype of VTEC O157:H7 colonisation in dairy calves. This subtype, VTEC O157:H7 (PT4;vtx(2;)vtx(2c)), is frequently isolated from Swedish cattle and has also been found to cause the majority of reported human infections in Sweden during the past 15 years. In most calves, inoculated with a representative strain of this specific subtype, the numbers of shed bacteria declined over the first two weeks. One calf could possibly be classified as a high-shedder, excreting high levels of the bacterium for a prolonged period.",2009 Oct 31,"['Jonsson, Malin E', 'Eriksson, Erik', 'Boqvist, Sofia', 'Urdahl, Anne Margrete', 'Aspán, Anna']",Acta Vet Scand,,,True
28cfe86a8fa13dacd3f447dcb095ac9a9f99a33a,PMC,Immunoglobulin Superfamily Virus Receptors and the Evolution of Adaptive Immunity,http://dx.doi.org/10.1371/journal.ppat.1000481,PMC2777377,19956667,CC BY,,2009 Nov 26,"['Dermody, Terence S.', 'Kirchner, Eva', 'Guglielmi, Kristen M.', 'Stehle, Thilo']",PLoS Pathog,,,True
10829aeda495398ba475afbd713e36bdc58cfcd0,PMC,Peptide-Mediated Cellular Delivery of Oligonucleotide-Based Therapeutics In Vitro: Quantitative Evaluation of Overall Efficacy Employing Easy to Handle Reporter Systems,http://dx.doi.org/10.2174/138161208786898806,PMC2778081,19075740,CC BY,"Cellular uptake of therapeutic oligonucleotides and subsequent intracellular trafficking to their target sites represents the major technical hurdle for the biological effectiveness of these potential drugs. Accordingly, laboratories worldwide focus on the development of suitable delivery systems. Among the different available non-viral systems like cationic polymers, cationic liposomes and polymeric nanoparticles, cell-penetrating peptides (CPPs) represent an attractive concept to bypass the problem of poor membrane permeability of these charged macromolecules. While uptake per se in most cases does not represent the main obstacle of nucleic acid delivery in vitro, it becomes increasingly apparent that intracellular trafficking is the bottleneck. As a consequence, in order to optimize a given delivery system, a side-by-side analysis of nucleic acid cargo internalized and the corresponding biological effect is required to determine the overall efficacy. In this review, we will concentrate on peptide-mediated delivery of siRNAs and steric block oligonucleotides and discuss different methods for quantitative assessment of the amount of cargo taken up and how to correlate those numbers with biological effects by applying easy to handle reporter systems. To illustrate current limitations of non-viral nucleic acid delivery systems, we present own data as an example and discuss options of how to enhance trafficking of molecules entrapped in cellular compartments.",2008 Dec,"['Laufer, S.D', 'Restle, T']",Curr Pharm Des,,,True
75cc9a3d0d2fc4baea735c4090944046019c8d39,PMC,"A Novel Enediynyl Peptide Inhibitor of Furin That Blocks Processing of proPDGF-A, B and proVEGF-C",http://dx.doi.org/10.1371/journal.pone.0007700,PMC2778948,19956642,CC BY,"BACKGROUND: Furin represents a crucial member of secretory mammalian subtilase, the Proprotein Convertase (PC) or Proprotein Convertase Subtilisin/Kexin (PCSK) superfamily. It has been linked to cancer, tumorgenesis, viral and bacterial pathogenesis. As a result it is considered a major target for intervention of these diseases. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we report, for the first time, the synthesis and biological evaluation of a newly designed potent furin inhibitor that contains a highly reactive beta-turn inducing and radical generating “enediynyl amino acid” (Eda) moiety. “Eda” was inserted between P1 and P1′ residues of hfurin(98–112) peptide, derived from the primary cleavage site of furin's own prodomain. The resulting hexadecapeptide derivative inhibited furin in vitro with IC(50) ∼40 nM when measured against the fluorogenic substrate Boc-RVRR-MCA. It also inhibited furin-mediated cleavage of a fluorogenic peptide derived from hSARS-CoV spike protein with IC(50) ∼193 nM. Additionally it also blocked furin-processing of growth factors proPDGF-A, B and VEGF-C that are linked to tumor genesis and cancer. Circular dichroism study showed that this inhibitor displayed a predominantly beta-turn structure while western blots confirmed its ability to protect furin protein from self degradation. CONCLUSION/SIGNIFICANCE: These findings imply its potential as a therapeutic agent for intervention of cancer and other furin-associated diseases.",2009 Nov 26,"['Basak, Ajoy', 'Khatib, Abdel-Majid', 'Mohottalage, Dayani', 'Basak, Sarmistha', 'Kolajova, Maria', 'Bag, Subhendu Sekhar', 'Basak, Amit']",PLoS One,,,True
7384db26f7f0a5f8c75844b2225b1783e6d783e5,PMC,"Human pregnancy-associated malaria-specific B cells target polymorphic, conformational epitopes in VAR2CSA",http://dx.doi.org/10.1111/j.1365-2958.2006.05503.x,PMC2779471,17176260,CC BY,"Pregnancy-associated malaria (PAM) is caused by Plasmodium falciparum-infected erythrocytes (IEs) that bind to chondroitin sulphate A (CSA) in the placenta by PAM-associated clonally variant surface antigens (VSA). Pregnancy-specific VSA (VSA(PAM)), which include the PfEMP1 variant VAR2CSA, are targets of IgG-mediated protective immunity to PAM. Here, we report an investigation of the specificity of naturally acquired immunity to PAM, using eight human monoclonal IgG1 antibodies that react exclusively with intact CSA-adhering IEs expressing VSA(PAM). Four reacted in Western blotting with high-molecular-weight (> 200 kDa) proteins, while seven reacted with either the DBL3-X or the DBL5-ε domains of VAR2CSA expressed either as Baculovirus constructs or on the surface of transfected Jurkat cells. We used a panel of recombinant antigens representing DBL3-X domains from P. falciparum field isolates to evaluate B-cell epitope diversity among parasite isolates, and identified the binding site of one monoclonal antibody using a chimeric DBL3-X construct. Our findings show that there is a high-frequency memory response to VSA(PAM), indicating that VAR2CSA is a primary target of naturally acquired PAM-specific protective immunity, and demonstrate the value of human monoclonal antibodies and conformationally intact recombinant antigens in VSA characterization.",2007 Jan,"['Barfod, Lea', 'Bernasconi, Nadia L', 'Dahlbäck, Madeleine', 'Jarrossay, David', 'Andersen, Pernille Haste', 'Salanti, Ali', 'Ofori, Michael F', 'Turner, Louise', 'Resende, Mafalda', 'Nielsen, Morten A', 'Theander, Thor G', 'Sallusto, Federica', 'Lanzavecchia, Antonio', 'Hviid, Lars']",Mol Microbiol,,,True
957ab1fcf790e8dd9d681f1f216287db1177cb78,PMC,Mathematical epidemiology is not an oxymoron,http://dx.doi.org/10.1186/1471-2458-9-S1-S2,PMC2779504,19922686,CC BY,"A brief description of the importance of communicable diseases in history and the development of mathematical modelling of disease transmission is given. This includes reasons for mathematical modelling, the history of mathematical modelling from the foundations laid in the late nineteenth century to the present, some of the accomplishments of mathematical modelling, and some challenges for the future. Our purpose is to demonstrate the importance of mathematical modelling for the understanding and management of infectious disease transmission.",2009 Nov 18,"Brauer, Fred",BMC Public Health,,,True
076d18c2ee294256a400299b5c4631aac187d47a,PMC,Early Assessment of Anxiety and Behavioral Response to Novel Swine-Origin Influenza A(H1N1),http://dx.doi.org/10.1371/journal.pone.0008032,PMC2779851,19997505,CC BY,"BACKGROUND: Since late April, 2009, a novel influenza virus A (H1N1), generally referred to as the “swine flu,” has spread around the globe and infected hundreds of thousands of people. During the first few days after the initial outbreak in Mexico, extensive media coverage together with a high degree of uncertainty about the transmissibility and mortality rate associated with the virus caused widespread concern in the population. The spread of an infectious disease can be strongly influenced by behavioral changes (e.g., social distancing) during the early phase of an epidemic, but data on risk perception and behavioral response to a novel virus is usually collected with a substantial delay or after an epidemic has run its course. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the results from an online survey that gathered data (n = 6,249) about risk perception of the Influenza A(H1N1) outbreak during the first few days of widespread media coverage (April 28 - May 5, 2009). We find that after an initially high level of concern, levels of anxiety waned along with the perception of the virus as an immediate threat. Overall, our data provide evidence that emotional status mediates behavioral response. Intriguingly, principal component analysis revealed strong clustering of anxiety about swine flu, bird flu and terrorism. All three of these threats receive a great deal of media attention and their fundamental uncertainty is likely to generate an inordinate amount of fear vis-a-vis their actual threat. CONCLUSIONS/SIGNIFICANCE: Our results suggest that respondents' behavior varies in predictable ways. Of particular interest, we find that affective variables, such as self-reported anxiety over the epidemic, mediate the likelihood that respondents will engage in protective behavior. Understanding how protective behavior such as social distancing varies and the specific factors that mediate it may help with the design of epidemic control strategies.",2009 Dec 3,"['Jones, James Holland', 'Salathé, Marcel']",PLoS One,,,True
53c533539d95b75bb8f88fe08e4693f299fd116e,PMC,Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells,http://dx.doi.org/10.1186/1465-9921-10-102,PMC2780994,19874627,CC BY,"BACKGROUND: Highly pathogenic avian influenza (HPAI) H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease. AIM: To study influenza A (H5N1) virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease. METHODS: We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces. RESULTS: We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our data suggests that viremia, secondary to, for example, gastro-intestinal infection, can potentially lead to infection of the lung. HPAI H5N1 virus was a more potent inducer of cytokines (e.g. IP-10, RANTES, IL-6) in comparison to H1N1 virus in alveolar epithelial cells, and these virus-induced chemokines were secreted onto both the apical and basolateral aspects of the polarized alveolar epithelium. CONCLUSION: The predilection of viruses for different routes of entry and egress from the infected cell is important in understanding the pathogenesis of influenza H5N1 infection and may help unravel the pathogenesis of human H5N1 disease.",2009 Oct 30,"['Chan, Michael CW', 'Chan, Renee WY', 'Yu, Wendy CL', 'Ho, Carol CC', 'Chui, WH', 'Lo, CK', 'Yuen, Kit M', 'Guan, Yi', 'Nicholls, John M', 'Peiris, JS Malik']",Respir Res,,,True
4961ab3b26b0165a3f1b267fc776329d792fc5f2,PMC,Comparison of distance measures in spatial analytical modeling for health service planning,http://dx.doi.org/10.1186/1472-6963-9-200,PMC2781002,19895692,CC BY,"BACKGROUND: Several methodological approaches have been used to estimate distance in health service research. In this study, focusing on cardiac catheterization services, Euclidean, Manhattan, and the less widely known Minkowski distance metrics are used to estimate distances from patient residence to hospital. Distance metrics typically produce less accurate estimates than actual measurements, but each metric provides a single model of travel over a given network. Therefore, distance metrics, unlike actual measurements, can be directly used in spatial analytical modeling. Euclidean distance is most often used, but unlikely the most appropriate metric. Minkowski distance is a more promising method. Distances estimated with each metric are contrasted with road distance and travel time measurements, and an optimized Minkowski distance is implemented in spatial analytical modeling. METHODS: Road distance and travel time are calculated from the postal code of residence of each patient undergoing cardiac catheterization to the pertinent hospital. The Minkowski metric is optimized, to approximate travel time and road distance, respectively. Distance estimates and distance measurements are then compared using descriptive statistics and visual mapping methods. The optimized Minkowski metric is implemented, via the spatial weight matrix, in a spatial regression model identifying socio-economic factors significantly associated with cardiac catheterization. RESULTS: The Minkowski coefficient that best approximates road distance is 1.54; 1.31 best approximates travel time. The latter is also a good predictor of road distance, thus providing the best single model of travel from patient's residence to hospital. The Euclidean metric and the optimal Minkowski metric are alternatively implemented in the regression model, and the results compared. The Minkowski method produces more reliable results than the traditional Euclidean metric. CONCLUSION: Road distance and travel time measurements are the most accurate estimates, but cannot be directly implemented in spatial analytical modeling. Euclidean distance tends to underestimate road distance and travel time; Manhattan distance tends to overestimate both. The optimized Minkowski distance partially overcomes their shortcomings; it provides a single model of travel over the network. The method is flexible, suitable for analytical modeling, and more accurate than the traditional metrics; its use ultimately increases the reliability of spatial analytical models.",2009 Nov 6,"['Shahid, Rizwan', 'Bertazzon, Stefania', 'Knudtson, Merril L', 'Ghali, William A']",BMC Health Serv Res,,,True
ad898b084d41c346f3da45e58960ae7925d52100,PMC,Influenza in Africa,http://dx.doi.org/10.1371/journal.pmed.1000182,PMC2782135,20016686,CC BY,"Maria Yazdanbakhsh and Peter Kremsner argue that there needs to be better awareness, surveillance, and clinical management of common febrile diseases in Africa, especially influenza.",2009 Dec 15,"['Yazdanbakhsh, Maria', 'Kremsner, Peter G.']",PLoS Med,,,True
2cbb038739adbd4487fa3c529e404189637e59d4,PMC,Rapid detection of ERG11 gene mutations in clinical Candida albicans isolates with reduced susceptibility to fluconazole by rolling circle amplification and DNA sequencing,http://dx.doi.org/10.1186/1471-2180-9-167,PMC2782262,19682357,CC BY,"BACKGROUND: Amino acid substitutions in the target enzyme Erg11p of azole antifungals contribute to clinically-relevant azole resistance in Candida albicans. A simple molecular method for rapid detection of ERG11 gene mutations would be an advantage as a screening tool to identify potentially-resistant strains and to track their movement. To complement DNA sequencing, we developed a padlock probe and rolling circle amplification (RCA)-based method to detect a series of mutations in the C. albicans ERG11 gene using ""reference"" azole-resistant isolates with known mutations. The method was then used to estimate the frequency of ERG11 mutations and their type in 25 Australian clinical C. albicans isolates with reduced susceptibility to fluconazole and in 23 fluconazole-susceptible isolates. RCA results were compared DNA sequencing. RESULTS: The RCA assay correctly identified all ERG11 mutations in eight ""reference"" C. albicans isolates. When applied to 48 test strains, the RCA method showed 100% agreement with DNA sequencing where an ERG11 mutation-specific probe was used. Of 20 different missense mutations detected by sequencing in 24 of 25 (96%) isolates with reduced fluconazole susceptibility, 16 were detected by RCA. Five missense mutations were detected by both methods in 18 of 23 (78%) fluconazole-susceptible strains. DNA sequencing revealed that mutations in non-susceptible isolates were all due to homozygous nucleotide changes. With the exception of the mutations leading to amino acid substitution E266D, those in fluconazole-susceptible strains were heterozygous. Amino acid substitutions common to both sets of isolates were D116E, E266D, K128T, V437I and V488I. Substitutions unique to isolates with reduced fluconazole susceptibility were G464 S (n = 4 isolates), G448E (n = 3), G307S (n = 3), K143R (n = 3) and Y123H, S405F and R467K (each n = 1). DNA sequencing revealed a novel substitution, G450V, in one isolate. CONCLUSION: The sensitive RCA assay described here is a simple, robust and rapid (2 h) method for the detection of ERG11 polymorphisms. It showed excellent concordance with ERG11 sequencing and is a potentially valuable tool to track the emergence and spread of azole-resistant C. albicans and to study the epidemiology of ERG11 mutations. The RCA method is applicable to the study of azole resistance in other fungi.",2009 Aug 14,"['Wang, Huiping', 'Kong, Fanrong', 'Sorrell, Tania C', 'Wang, Bin', 'McNicholas, Paul', 'Pantarat, Namfon', 'Ellis, David', 'Xiao, Meng', 'Widmer, Fred', 'Chen, Sharon CA']",BMC Microbiol,,,True
41c7a01f11ed47591d99f45774e43e45aeba0619,PMC,CAPIH: A Web interface for comparative analyses and visualization of host-HIV protein-protein interactions,http://dx.doi.org/10.1186/1471-2180-9-164,PMC2782265,19674441,CC BY,"BACKGROUND: The Human Immunodeficiency Virus type one (HIV-1) is the major causing pathogen of the Acquired Immune Deficiency Syndrome (AIDS). A large number of HIV-1-related studies are based on three non-human model animals: chimpanzee, rhesus macaque, and mouse. However, the differences in host-HIV-1 interactions between human and these model organisms have remained unexplored. DESCRIPTION: Here we present CAPIH (Comparative Analysis of Protein Interactions for HIV-1), the first web-based interface to provide comparative information between human and the three model organisms in the context of host-HIV-1 protein interactions. CAPIH identifies genetic changes that occur in HIV-1-interacting host proteins. In a total of 1,370 orthologous protein sets, CAPIH identifies ~86,000 amino acid substitutions, ~21,000 insertions/deletions, and ~33,000 potential post-translational modifications that occur only in one of the four compared species. CAPIH also provides an interactive interface to display the host-HIV-1 protein interaction networks, the presence/absence of orthologous proteins in the model organisms in the networks, the genetic changes that occur in the protein nodes, and the functional domains and potential protein interaction hot sites that may be affected by the genetic changes. The CAPIH interface is freely accessible at http://bioinfo-dbb.nhri.org.tw/capih. CONCLUSION: CAPIH exemplifies that large divergences exist in disease-associated proteins between human and the model animals. Since all of the newly developed medications must be tested in model animals before entering clinical trials, it is advisable that comparative analyses be performed to ensure proper translations of animal-based studies. In the case of AIDS, the host-HIV-1 protein interactions apparently have differed to a great extent among the compared species. An integrated protein network comparison among the four species will probably shed new lights on AIDS studies.",2009 Aug 12,"['Lin, Fan-Kai', 'Pan, Chia-Lin', 'Yang, Jinn-Moon', 'Chuang, Trees-Juen', 'Chen, Feng-Chi']",BMC Microbiol,,,True
1638100b254164ee9af7d66be61794a7efa07b78,PMC,Pulmonary fibrosis induced by H5N1 viral infection in mice,http://dx.doi.org/10.1186/1465-9921-10-107,PMC2783028,19909524,CC BY,"BACKGROUND: Inflammatory process results in lung injury that may lead to pulmonary fibrosis (PF). Here, we described PF in mice infected with H5N1 virus. METHODS: Eight-week-old BALB/c mice were inoculated intranasally with 1 × 10(1 )MID(50 )of A/Chicken/Hebei/108/2002(H5N1) viruses. Lung injury/fibrosis was evaluated by observation of hydroxyproline concentrations, lung indexes, and histopathology on days 7, 14, and 30 postinoculation. RESULTS: H5N1-inoculated mice presented two stages of pulmonary disease over a 30-d period after infection. At acute stage, infected-mice showed typical diffuse pneumonia with inflammatory cellular infiltration, alveolar and interstitial edema and hemorrhage on day 7 postinoculation. At restoration stage, most infected-mice developed PF of different severities on day 30 postinoculation, and 18% of the survived mice underwent severe interstitial and intra-alveolar fibrosis with thickened alveolar walls, collapsed alveoli and large fibrotic areas. The dramatically elevated hydroxyproline levels in H5N1-infected mice showed deposition of collagen in lungs, and confirmed fibrosis of lungs. The dry lung-to-body weight ratio was significantly increased in infected group, which might be associated with the formation of PF in H5N1-infected mice. CONCLUSION: Our findings show that H5N1-infected mice develop the typical PF during restoration period, which will contribute to the investigation of fibrogenesis and potential therapeutic intervention in human H5N1 disease.",2009 Nov 12,"['Qiao, Jian', 'Zhang, Miaojie', 'Bi, Jianmin', 'Wang, Xun', 'Deng, Guangcun', 'He, Guimei', 'Luan, Zhihua', 'Lv, Nana', 'Xu, Tong', 'Zhao, Lihong']",Respir Res,,,True
513a25eb7a96ba7f7ae433498caf4791eb19e97c,PMC,Apolipoprotein D in Lipid Metabolism and Its Functional                         Implication in Atherosclerosis and Aging,,PMC2784685,19946382,CC BY,"Dyslipidemia is characterized by increased triglyceride and low-density lipoprotein (LDL) levels, and decreased high-density lipoprotein (HDL) levels. Such an atherogenic lipid profile often predisposes an at risk individual to coronary artery disease with incompletely understood mechanisms. Apolipoprotein D (apoD) is an atypical apolipoprotein. Unlike canonical apolipoproteins that are produced mainly in liver and intestine, apoD is expressed widely in mammalian tissues. ApoD does not share significant degrees of homology in amino acid sequence with other apolipoproteins. Instead, apoD is structurally similar to lipocalins, a diverse family of lipid-binding proteins that are responsible for transporting lipids and other small hydrophobic molecules for metabolism. Plasma ApoD is present mainly in HDL and to a lesser extent in low density lipoproteins (LDL) and very low-density lipoproteins (VLDL). Genetic variants of apoD are associated with abnormal lipid metabolism and increased risk of developing metabolic syndrome. Increased apoD deposition is detectable in atherosclerotic lesions of humans with established cardiovascular disease as well as mice with premature atherosclerosis. Moreover, apoD is associated with anti-oxidation and anti-stress activities, contributing to lifespan expansion in fruit flies. Elderly subjects and patients with Alzheimer exhibit markedly elevated apoD production in the brain. Thus, apoD is emerged as a significant player in lipid metabolism and aging. Here we focus our review on recent advances toward our understanding of apoD in lipid metabolism and address whether apoD dysregulation contributes to the pathogenesis of dyslipidemia and atherosclerosis. We will also discuss the functional implication of apoD in aging.",2008 Dec 12,"['Perdomo, German', 'Dong, H. Henry']",Aging (Albany NY),,,True
da867b3ea92b5191c4fbdc4d09c0712a73da7766,PMC,A “One Health” Approach to Address Emerging Zoonoses: The HALI Project in Tanzania,http://dx.doi.org/10.1371/journal.pmed.1000190,PMC2784942,20016689,CC BY,"Jonna Mazet and colleagues describe their work in the Tanzania-based HALI Project, which adopts the “One Health” approach to address emerging zoonoses and that recognizes the interconnectedness of human, animal, and environmental health.",2009 Dec 15,"['Mazet, Jonna A. K.', 'Clifford, Deana L.', 'Coppolillo, Peter B.', 'Deolalikar, Anil B.', 'Erickson, Jon D.', 'Kazwala, Rudovick R.']",PLoS Med,,,True
57694e4ef5e2af0338dc7ba54cf154b2b0cdda76,PMC,Automated vocabulary discovery for geo-parsing online epidemic intelligence,http://dx.doi.org/10.1186/1471-2105-10-385,PMC2787530,19930702,CC BY,"BACKGROUND: Automated surveillance of the Internet provides a timely and sensitive method for alerting on global emerging infectious disease threats. HealthMap is part of a new generation of online systems designed to monitor and visualize, on a real-time basis, disease outbreak alerts as reported by online news media and public health sources. HealthMap is of specific interest for national and international public health organizations and international travelers. A particular task that makes such a surveillance useful is the automated discovery of the geographic references contained in the retrieved outbreak alerts. This task is sometimes referred to as ""geo-parsing"". A typical approach to geo-parsing would demand an expensive training corpus of alerts manually tagged by a human. RESULTS: Given that human readers perform this kind of task by using both their lexical and contextual knowledge, we developed an approach which relies on a relatively small expert-built gazetteer, thus limiting the need of human input, but focuses on learning the context in which geographic references appear. We show in a set of experiments, that this approach exhibits a substantial capacity to discover geographic locations outside of its initial lexicon. CONCLUSION: The results of this analysis provide a framework for future automated global surveillance efforts that reduce manual input and improve timeliness of reporting.",2009 Nov 24,"['Keller, Mikaela', 'Freifeld, Clark C', 'Brownstein, John S']",BMC Bioinformatics,,,True
08e78c0222e84457195ccefb2e371f1847670436,PMC,"Establishment, Immortalisation and Characterisation of Pteropid Bat Cell Lines",http://dx.doi.org/10.1371/journal.pone.0008266,PMC2788226,20011515,CC BY,"BACKGROUND: Bats are the suspected natural reservoir hosts for a number of new and emerging zoonotic viruses including Nipah virus, Hendra virus, severe acute respiratory syndrome coronavirus and Ebola virus. Since the discovery of SARS-like coronaviruses in Chinese horseshoe bats, attempts to isolate a SL-CoV from bats have failed and attempts to isolate other bat-borne viruses in various mammalian cell lines have been similarly unsuccessful. New stable bat cell lines are needed to help with these investigations and as tools to assist in the study of bat immunology and virus-host interactions. METHODOLOGY/FINDINGS: Black flying foxes (Pteropus alecto) were captured from the wild and transported live to the laboratory for primary cell culture preparation using a variety of different methods and culture media. Primary cells were successfully cultured from 20 different organs. Cell immortalisation can occur spontaneously, however we used a retroviral system to immortalise cells via the transfer and stable production of the Simian virus 40 Large T antigen and the human telomerase reverse transcriptase protein. Initial infection experiments with both cloned and uncloned cell lines using Hendra and Nipah viruses demonstrated varying degrees of infection efficiency between the different cell lines, although it was possible to infect cells in all tissue types. CONCLUSIONS/SIGNIFICANCE: The approaches developed and optimised in this study should be applicable to bats of other species. We are in the process of generating further cell lines from a number of different bat species using the methodology established in this study.",2009 Dec 11,"['Crameri, Gary', 'Todd, Shawn', 'Grimley, Samantha', 'McEachern, Jennifer A.', 'Marsh, Glenn A.', 'Smith, Craig', 'Tachedjian, Mary', 'De Jong, Carol', 'Virtue, Elena R.', 'Yu, Meng', 'Bulach, Dieter', 'Liu, Jun-Ping', 'Michalski, Wojtek P.', 'Middleton, Deborah', 'Field, Hume E.', 'Wang, Lin-Fa']",PLoS One,,,True
3799479a8ad2b8db9f21c68f88dfae6410d0fed0,PMC,A comprehensive assessment of N-terminal signal peptides prediction methods,http://dx.doi.org/10.1186/1471-2105-10-S15-S2,PMC2788353,19958512,CC BY,"BACKGROUND: Amino-terminal signal peptides (SPs) are short regions that guide the targeting of secretory proteins to the correct subcellular compartments in the cell. They are cleaved off upon the passenger protein reaching its destination. The explosive growth in sequencing technologies has led to the deposition of vast numbers of protein sequences necessitating rapid functional annotation techniques, with subcellular localization being a key feature. Of the myriad software prediction tools developed to automate the task of assigning the SP cleavage site of these new sequences, we review here, the performance and reliability of commonly used SP prediction tools. RESULTS: The available signal peptide data has been manually curated and organized into three datasets representing eukaryotes, Gram-positive and Gram-negative bacteria. These datasets are used to evaluate thirteen prediction tools that are publicly available. SignalP (both the HMM and ANN versions) maintains consistency and achieves the best overall accuracy in all three benchmarking experiments, ranging from 0.872 to 0.914 although other prediction tools are narrowing the performance gap. CONCLUSION: The majority of the tools evaluated in this study encounter no difficulty in discriminating between secretory and non-secretory proteins. The challenge clearly remains with pinpointing the correct SP cleavage site. The composite scoring schemes employed by SignalP may help to explain its accuracy. Prediction task is divided into a number of separate steps, thus allowing each score to tackle a particular aspect of the prediction.",2009 Dec 3,"['Choo, Khar Heng', 'Tan, Tin Wee', 'Ranganathan, Shoba']",BMC Bioinformatics,,,True
30f0103086a7458f1bdb18024f372814d88a9b4e,PMC,Efficient Assembly and Secretion of Recombinant Subviral Particles of the Four Dengue Serotypes Using Native prM and E Proteins,http://dx.doi.org/10.1371/journal.pone.0008325,PMC2790604,20016834,CC BY,"BACKGROUND: Flavivirus infected cells produce infectious virions and subviral particles, both of which are formed by the assembly of prM and E envelope proteins and are believed to undergo the same maturation process. Dengue recombinant subviral particles have been produced in cell cultures with either modified or chimeric proteins but not using the native forms of prM and E. METHODOLOGY/PRINCIPAL FINDINGS: We have used a codon optimization strategy to obtain an efficient expression of native viral proteins and production of recombinant subviral particles (RSPs) for all four dengue virus (DV) serotypes. A stable HeLa cell line expressing DV1 prME was established (HeLa-prME) and RSPs were analyzed by immunofluorescence and transmission electron microscopy. We found that E protein is mainly present in the endoplasmic reticulum (ER) where assembly of RSPs could be observed. Biochemical characterization of DV1 RSPs secretion revealed both prM protein cleavage and homodimerization of E proteins before their release into the supernatant, indicating that RSPs undergo a similar maturation process as dengue virus. Pulse chase experiment showed that 8 hours are required for the secretion of DV1 RSPs. We have used HeLa-prME to develop a semi-quantitative assay and screened a human siRNA library targeting genes involved in membrane trafficking. Knockdown of 23 genes resulted in a significant reduction in DV RSP secretion, whereas for 22 others we observed an increase of RSP levels in cell supernatant. CONCLUSIONS/SIGNIFICANCE: Our data describe the efficient production of RSPs containing native prM and E envelope proteins for all dengue serotypes. Dengue RSPs and corresponding producing cell lines are safe and novel tools that can be used in the study of viral egress as well as in the development of vaccine and drugs against dengue virus.",2009 Dec 15,"['Wang, Pei-Gang', 'Kudelko, Mateusz', 'Lo, Joanne', 'Siu, Lewis Yu Lam', 'Kwok, Kevin Tsz Hin', 'Sachse, Martin', 'Nicholls, John M.', 'Bruzzone, Roberto', 'Altmeyer, Ralf M.', 'Nal, Béatrice']",PLoS One,,,True
8e4a1132b0301964add6af40ca83b222d7f6d9e3,PMC,Rhodopsin Molecular Evolution in Mammals Inhabiting Low Light Environments,http://dx.doi.org/10.1371/journal.pone.0008326,PMC2790605,20016835,CC BY,"The ecological radiation of mammals to inhabit a variety of light environments is largely attributed to adaptive changes in their visual systems. Visual capabilities are conferred by anatomical features of the eyes as well as the combination and properties of their constituent light sensitive pigments. To test whether evolutionary switches to different niches characterized by dim-light conditions coincided with molecular adaptation of the rod pigment rhodopsin, we sequenced the rhodopsin gene in twenty-two mammals including several bats and subterranean mole-rats. We compared these to thirty-seven published mammal rhodopsin sequences, from species with divergent visual ecologies, including nocturnal, diurnal and aquatic groups. All taxa possessed an intact functional rhodopsin; however, phylogenetic tree reconstruction recovered a gene tree in which rodents were not monophyletic, and also in which echolocating bats formed a monophyletic group. These conflicts with the species tree appear to stem from accelerated evolution in these groups, both of which inhabit low light environments. Selection tests confirmed divergent selection pressures in the clades of subterranean rodents and bats, as well as in marine mammals that live in turbid conditions. We also found evidence of divergent selection pressures among groups of bats with different sensory modalities based on vision and echolocation. Sliding window analyses suggest most changes occur in transmembrane domains, particularly obvious within the pinnipeds; however, we found no obvious pattern between photopic niche and predicted spectral sensitivity based on known critical amino acids. This study indicates that the independent evolution of rhodopsin vision in ecologically specialised groups of mammals has involved molecular evolution at the sequence level, though such changes might not mediate spectral sensitivity directly.",2009 Dec 16,"['Zhao, Huabin', 'Ru, Binghua', 'Teeling, Emma C.', 'Faulkes, Christopher G.', 'Zhang, Shuyi', 'Rossiter, Stephen J.']",PLoS One,,,True
a3b545a34bc8511e9c5fd6ff71443e92bd6cc915,PMC,Rhodopsin Molecular Evolution in Mammals Inhabiting Low Light Environments,http://dx.doi.org/10.1371/journal.pone.0008326,PMC2790605,20016835,CC BY,"The ecological radiation of mammals to inhabit a variety of light environments is largely attributed to adaptive changes in their visual systems. Visual capabilities are conferred by anatomical features of the eyes as well as the combination and properties of their constituent light sensitive pigments. To test whether evolutionary switches to different niches characterized by dim-light conditions coincided with molecular adaptation of the rod pigment rhodopsin, we sequenced the rhodopsin gene in twenty-two mammals including several bats and subterranean mole-rats. We compared these to thirty-seven published mammal rhodopsin sequences, from species with divergent visual ecologies, including nocturnal, diurnal and aquatic groups. All taxa possessed an intact functional rhodopsin; however, phylogenetic tree reconstruction recovered a gene tree in which rodents were not monophyletic, and also in which echolocating bats formed a monophyletic group. These conflicts with the species tree appear to stem from accelerated evolution in these groups, both of which inhabit low light environments. Selection tests confirmed divergent selection pressures in the clades of subterranean rodents and bats, as well as in marine mammals that live in turbid conditions. We also found evidence of divergent selection pressures among groups of bats with different sensory modalities based on vision and echolocation. Sliding window analyses suggest most changes occur in transmembrane domains, particularly obvious within the pinnipeds; however, we found no obvious pattern between photopic niche and predicted spectral sensitivity based on known critical amino acids. This study indicates that the independent evolution of rhodopsin vision in ecologically specialised groups of mammals has involved molecular evolution at the sequence level, though such changes might not mediate spectral sensitivity directly.",2009 Dec 16,"['Zhao, Huabin', 'Ru, Binghua', 'Teeling, Emma C.', 'Faulkes, Christopher G.', 'Zhang, Shuyi', 'Rossiter, Stephen J.']",PLoS One,,,False
c8be435bb37880f219f7c0c124a6acf18df46e07,PMC,Rhodopsin Molecular Evolution in Mammals Inhabiting Low Light Environments,http://dx.doi.org/10.1371/journal.pone.0008326,PMC2790605,20016835,CC BY,"The ecological radiation of mammals to inhabit a variety of light environments is largely attributed to adaptive changes in their visual systems. Visual capabilities are conferred by anatomical features of the eyes as well as the combination and properties of their constituent light sensitive pigments. To test whether evolutionary switches to different niches characterized by dim-light conditions coincided with molecular adaptation of the rod pigment rhodopsin, we sequenced the rhodopsin gene in twenty-two mammals including several bats and subterranean mole-rats. We compared these to thirty-seven published mammal rhodopsin sequences, from species with divergent visual ecologies, including nocturnal, diurnal and aquatic groups. All taxa possessed an intact functional rhodopsin; however, phylogenetic tree reconstruction recovered a gene tree in which rodents were not monophyletic, and also in which echolocating bats formed a monophyletic group. These conflicts with the species tree appear to stem from accelerated evolution in these groups, both of which inhabit low light environments. Selection tests confirmed divergent selection pressures in the clades of subterranean rodents and bats, as well as in marine mammals that live in turbid conditions. We also found evidence of divergent selection pressures among groups of bats with different sensory modalities based on vision and echolocation. Sliding window analyses suggest most changes occur in transmembrane domains, particularly obvious within the pinnipeds; however, we found no obvious pattern between photopic niche and predicted spectral sensitivity based on known critical amino acids. This study indicates that the independent evolution of rhodopsin vision in ecologically specialised groups of mammals has involved molecular evolution at the sequence level, though such changes might not mediate spectral sensitivity directly.",2009 Dec 16,"['Zhao, Huabin', 'Ru, Binghua', 'Teeling, Emma C.', 'Faulkes, Christopher G.', 'Zhang, Shuyi', 'Rossiter, Stephen J.']",PLoS One,,,False
cc49a6aeb47e524e172e40b0633745f66ac04f5b,PMC,Rhodopsin Molecular Evolution in Mammals Inhabiting Low Light Environments,http://dx.doi.org/10.1371/journal.pone.0008326,PMC2790605,20016835,CC BY,"The ecological radiation of mammals to inhabit a variety of light environments is largely attributed to adaptive changes in their visual systems. Visual capabilities are conferred by anatomical features of the eyes as well as the combination and properties of their constituent light sensitive pigments. To test whether evolutionary switches to different niches characterized by dim-light conditions coincided with molecular adaptation of the rod pigment rhodopsin, we sequenced the rhodopsin gene in twenty-two mammals including several bats and subterranean mole-rats. We compared these to thirty-seven published mammal rhodopsin sequences, from species with divergent visual ecologies, including nocturnal, diurnal and aquatic groups. All taxa possessed an intact functional rhodopsin; however, phylogenetic tree reconstruction recovered a gene tree in which rodents were not monophyletic, and also in which echolocating bats formed a monophyletic group. These conflicts with the species tree appear to stem from accelerated evolution in these groups, both of which inhabit low light environments. Selection tests confirmed divergent selection pressures in the clades of subterranean rodents and bats, as well as in marine mammals that live in turbid conditions. We also found evidence of divergent selection pressures among groups of bats with different sensory modalities based on vision and echolocation. Sliding window analyses suggest most changes occur in transmembrane domains, particularly obvious within the pinnipeds; however, we found no obvious pattern between photopic niche and predicted spectral sensitivity based on known critical amino acids. This study indicates that the independent evolution of rhodopsin vision in ecologically specialised groups of mammals has involved molecular evolution at the sequence level, though such changes might not mediate spectral sensitivity directly.",2009 Dec 16,"['Zhao, Huabin', 'Ru, Binghua', 'Teeling, Emma C.', 'Faulkes, Christopher G.', 'Zhang, Shuyi', 'Rossiter, Stephen J.']",PLoS One,,,False
6e1ec9619b8e1f05cb76a414941e6eecb198ae07,PMC,Rhodopsin Molecular Evolution in Mammals Inhabiting Low Light Environments,http://dx.doi.org/10.1371/journal.pone.0008326,PMC2790605,20016835,CC BY,"The ecological radiation of mammals to inhabit a variety of light environments is largely attributed to adaptive changes in their visual systems. Visual capabilities are conferred by anatomical features of the eyes as well as the combination and properties of their constituent light sensitive pigments. To test whether evolutionary switches to different niches characterized by dim-light conditions coincided with molecular adaptation of the rod pigment rhodopsin, we sequenced the rhodopsin gene in twenty-two mammals including several bats and subterranean mole-rats. We compared these to thirty-seven published mammal rhodopsin sequences, from species with divergent visual ecologies, including nocturnal, diurnal and aquatic groups. All taxa possessed an intact functional rhodopsin; however, phylogenetic tree reconstruction recovered a gene tree in which rodents were not monophyletic, and also in which echolocating bats formed a monophyletic group. These conflicts with the species tree appear to stem from accelerated evolution in these groups, both of which inhabit low light environments. Selection tests confirmed divergent selection pressures in the clades of subterranean rodents and bats, as well as in marine mammals that live in turbid conditions. We also found evidence of divergent selection pressures among groups of bats with different sensory modalities based on vision and echolocation. Sliding window analyses suggest most changes occur in transmembrane domains, particularly obvious within the pinnipeds; however, we found no obvious pattern between photopic niche and predicted spectral sensitivity based on known critical amino acids. This study indicates that the independent evolution of rhodopsin vision in ecologically specialised groups of mammals has involved molecular evolution at the sequence level, though such changes might not mediate spectral sensitivity directly.",2009 Dec 16,"['Zhao, Huabin', 'Ru, Binghua', 'Teeling, Emma C.', 'Faulkes, Christopher G.', 'Zhang, Shuyi', 'Rossiter, Stephen J.']",PLoS One,,,False
7bf733ca3c79a629454e7fb356e9510ddc219831,PMC,Rhodopsin Molecular Evolution in Mammals Inhabiting Low Light Environments,http://dx.doi.org/10.1371/journal.pone.0008326,PMC2790605,20016835,CC BY,"The ecological radiation of mammals to inhabit a variety of light environments is largely attributed to adaptive changes in their visual systems. Visual capabilities are conferred by anatomical features of the eyes as well as the combination and properties of their constituent light sensitive pigments. To test whether evolutionary switches to different niches characterized by dim-light conditions coincided with molecular adaptation of the rod pigment rhodopsin, we sequenced the rhodopsin gene in twenty-two mammals including several bats and subterranean mole-rats. We compared these to thirty-seven published mammal rhodopsin sequences, from species with divergent visual ecologies, including nocturnal, diurnal and aquatic groups. All taxa possessed an intact functional rhodopsin; however, phylogenetic tree reconstruction recovered a gene tree in which rodents were not monophyletic, and also in which echolocating bats formed a monophyletic group. These conflicts with the species tree appear to stem from accelerated evolution in these groups, both of which inhabit low light environments. Selection tests confirmed divergent selection pressures in the clades of subterranean rodents and bats, as well as in marine mammals that live in turbid conditions. We also found evidence of divergent selection pressures among groups of bats with different sensory modalities based on vision and echolocation. Sliding window analyses suggest most changes occur in transmembrane domains, particularly obvious within the pinnipeds; however, we found no obvious pattern between photopic niche and predicted spectral sensitivity based on known critical amino acids. This study indicates that the independent evolution of rhodopsin vision in ecologically specialised groups of mammals has involved molecular evolution at the sequence level, though such changes might not mediate spectral sensitivity directly.",2009 Dec 16,"['Zhao, Huabin', 'Ru, Binghua', 'Teeling, Emma C.', 'Faulkes, Christopher G.', 'Zhang, Shuyi', 'Rossiter, Stephen J.']",PLoS One,,,False
d2595ff8328dfa3ea1479890056006db702b95c1,PMC,Rhodopsin Molecular Evolution in Mammals Inhabiting Low Light Environments,http://dx.doi.org/10.1371/journal.pone.0008326,PMC2790605,20016835,CC BY,"The ecological radiation of mammals to inhabit a variety of light environments is largely attributed to adaptive changes in their visual systems. Visual capabilities are conferred by anatomical features of the eyes as well as the combination and properties of their constituent light sensitive pigments. To test whether evolutionary switches to different niches characterized by dim-light conditions coincided with molecular adaptation of the rod pigment rhodopsin, we sequenced the rhodopsin gene in twenty-two mammals including several bats and subterranean mole-rats. We compared these to thirty-seven published mammal rhodopsin sequences, from species with divergent visual ecologies, including nocturnal, diurnal and aquatic groups. All taxa possessed an intact functional rhodopsin; however, phylogenetic tree reconstruction recovered a gene tree in which rodents were not monophyletic, and also in which echolocating bats formed a monophyletic group. These conflicts with the species tree appear to stem from accelerated evolution in these groups, both of which inhabit low light environments. Selection tests confirmed divergent selection pressures in the clades of subterranean rodents and bats, as well as in marine mammals that live in turbid conditions. We also found evidence of divergent selection pressures among groups of bats with different sensory modalities based on vision and echolocation. Sliding window analyses suggest most changes occur in transmembrane domains, particularly obvious within the pinnipeds; however, we found no obvious pattern between photopic niche and predicted spectral sensitivity based on known critical amino acids. This study indicates that the independent evolution of rhodopsin vision in ecologically specialised groups of mammals has involved molecular evolution at the sequence level, though such changes might not mediate spectral sensitivity directly.",2009 Dec 16,"['Zhao, Huabin', 'Ru, Binghua', 'Teeling, Emma C.', 'Faulkes, Christopher G.', 'Zhang, Shuyi', 'Rossiter, Stephen J.']",PLoS One,,,False
506b8507912862c6a87723c6a5babf2132748503,PMC,Expanding the Paradigms of Plant Pathogen Life History and Evolution of Parasitic Fitness beyond Agricultural Boundaries,http://dx.doi.org/10.1371/journal.ppat.1000693,PMC2790610,20041212,CC BY,,2009 Dec 24,"['Morris, Cindy E.', 'Bardin, Marc', 'Kinkel, Linda L.', 'Moury, Benoit', 'Nicot, Philippe C.', 'Sands, David C.']",PLoS Pathog,,,True
cf6c6fa2a4cf3fd624d4ef8291804a3fab3f1b2a,PMC,The SARS Coronavirus 3a Protein Causes Endoplasmic Reticulum Stress and Induces Ligand-Independent Downregulation of the Type 1 Interferon Receptor,http://dx.doi.org/10.1371/journal.pone.0008342,PMC2791231,20020050,CC BY,"The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is reported to cause apoptosis of infected cells and several of its proteins including the 3a accessory protein, are pro-apoptotic. Since the 3a protein localizes to the endoplasmic reticulum (ER)-Golgi compartment, its role in causing ER stress was investigated in transiently transfected cells. Cells expressing the 3a proteins showed ER stress based on activation of genes for the ER chaperones GRP78 and GRP94. Since ER stress can cause differential modulation of the unfolded protein response (UPR), which includes the inositol-requiring enzyme 1 (IRE-1), activating transcription factor 6 (ATF6) and PKR-like ER kinase (PERK) pathways, these were individually tested in 3a-expressing cells. Only the PERK pathway was found to be activated in 3a-expressing cells based on (1) increased phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) and inhibitory effects of a dominant-negative form of eIF2α on GRP78 promoter activity, (2) increased translation of activating transcription factor 4 (ATF4) mRNA, and (3) ATF4-dependent activation of the C/EBP homologous protein (CHOP) gene promoter. Activation of PERK affects innate immunity by suppression of type 1 interferon (IFN) signaling. The 3a protein was found to induce serine phosphorylation within the IFN alpha-receptor subunit 1 (IFNAR1) degradation motif and to increase IFNAR1 ubiquitination. Confocal microscopic analysis showed increased translocation of IFNAR1 into the lysosomal compartment and flow cytometry showed reduced levels of IFNAR1 in 3a-expressing cells. These results provide further mechanistic details of the pro-apoptotic effects of the SARS-CoV 3a protein, and suggest a potential role for it in attenuating interferon responses and innate immunity.",2009 Dec 17,"['Minakshi, Rinki', 'Padhan, Kartika', 'Rani, Manjusha', 'Khan, Nabab', 'Ahmad, Faizan', 'Jameel, Shahid']",PLoS One,,,True
557a14f4857aab6fa0b5d3b980aa241b113977ba,PMC,Breaking the Waves: Modelling the Potential Impact of Public Health Measures to Defer the Epidemic Peak of Novel Influenza A/H1N1,http://dx.doi.org/10.1371/journal.pone.0008356,PMC2791869,20027293,CC BY,"BACKGROUND: On June 11, 2009, the World Health Organization declared phase 6 of the novel influenza A/H1N1 pandemic. Although by the end of September 2009, the novel virus had been reported from all continents, the impact in most countries of the northern hemisphere has been limited. The return of the virus in a second wave would encounter populations that are still nonimmune and not vaccinated yet. We modelled the effect of control strategies to reduce the spread with the goal to defer the epidemic wave in a country where it is detected in a very early stage. METHODOLOGY/PRINCIPAL FINDINGS: We constructed a deterministic SEIR model using the age distribution and size of the population of Germany based on the observed number of imported cases and the early findings for the epidemiologic characteristics described by Fraser (Science, 2009). We propose a two-step control strategy with an initial effort to trace, quarantine, and selectively give prophylactic treatment to contacts of the first 100 to 500 cases. In the second step, the same measures are focused on the households of the next 5,000 to 10,000 cases. As a result, the peak of the epidemic could be delayed up to 7.6 weeks if up to 30% of cases are detected. However, the cumulative attack rates would not change. Necessary doses of antivirals would be less than the number of treatment courses for 0.1% of the population. In a sensitivity analysis, both case detection rate and the variation of R0 have major effects on the resulting delay. CONCLUSIONS/SIGNIFICANCE: Control strategies that reduce the spread of the disease during the early phase of a pandemic wave may lead to a substantial delay of the epidemic. Since prophylactic treatment is only offered to the contacts of the first 10,000 cases, the amount of antivirals needed is still very limited.",2009 Dec 21,"['an der Heiden, Matthias', 'Buchholz, Udo', 'Krause, Gérard', 'Kirchner, Göran', 'Claus, Hermann', 'Haas, Walter H.']",PLoS One,,,True
7045ec55df870b7d611154081ae7e469883f64c4,PMC,Aurintricarboxylic Acid Is a Potent Inhibitor of Influenza A and B Virus Neuraminidases,http://dx.doi.org/10.1371/journal.pone.0008350,PMC2792043,20020057,CC BY,"BACKGROUND: Influenza viruses cause serious infections that can be prevented or treated using vaccines or antiviral agents, respectively. While vaccines are effective, they have a number of limitations, and influenza strains resistant to currently available anti-influenza drugs are increasingly isolated. This necessitates the exploration of novel anti-influenza therapies. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the potential of aurintricarboxylic acid (ATA), a potent inhibitor of nucleic acid processing enzymes, to protect Madin-Darby canine kidney cells from influenza infection. We found, by neutral red assay, that ATA was protective, and by RT-PCR and ELISA, respectively, confirmed that ATA reduced viral replication and release. Furthermore, while pre-treating cells with ATA failed to inhibit viral replication, pre-incubation of virus with ATA effectively reduced viral titers, suggesting that ATA may elicit its inhibitory effects by directly interacting with the virus. Electron microscopy revealed that ATA induced viral aggregation at the cell surface, prompting us to determine if ATA could inhibit neuraminidase. ATA was found to compromise the activities of virus-derived and recombinant neuraminidase. Moreover, an oseltamivir-resistant H1N1 strain with H274Y was also found to be sensitive to ATA. Finally, we observed additive protective value when infected cells were simultaneously treated with ATA and amantadine hydrochloride, an anti-influenza drug that inhibits M2-ion channels of influenza A virus. CONCLUSIONS/SIGNIFICANCE: Collectively, these data suggest that ATA is a potent anti-influenza agent by directly inhibiting the neuraminidase and could be a more effective antiviral compound when used in combination with amantadine hydrochloride.",2009 Dec 17,"['Hashem, Anwar M.', 'Flaman, Anathea S.', 'Farnsworth, Aaron', 'Brown, Earl G.', 'Van Domselaar, Gary', 'He, Runtao', 'Li, Xuguang']",PLoS One,,,True
0ced1f946cce007aa319a0ba38aef2c4b14dab0e,PMC,Identification of a novel conserved HLA-A*0201-restricted epitope from the spike protein of SARS-CoV,http://dx.doi.org/10.1186/1471-2172-10-61,PMC2792222,19958537,CC BY,"BACKGROUND: The spike (S) protein is a major structural glycoprotein of coronavirus (CoV), the causal agent of severe acute respiratory syndrome (SARS). The S protein is a potent target for SARS-specific cell-mediated immune responses. However, the mechanism CoV pathogenesis in SARS and the role of special CTLs in virus clearance are still largely uncharacterized. Here, we describe a study that leads to the identification of a novel HLA-A*0201-restricted epitope from conserved regions of S protein. RESULTS: First, different SARS-CoV sequences were analyzed to predict eight candidate peptides from conserved regions of the S protein based upon HLA-A*0201 binding and proteosomal cleavage. Four of eight candidate peptides were tested by HLA-A*0201 binding assays. Among the four candidate peptides, Sp8 (S(958-966), VLNDILSRL) induced specific CTLs both ex vivo in PBLs of healthy HLA-A2(+ )donors and in HLA-A2.1/K(b )transgenic mice immunized with a plasmid encoding full-length S protein. The immunized mice released IFN-γ and lysed target cells upon stimulation with Sp8 peptide-pulsed autologous dendritic cells in comparison to other candidates. CONCLUSION: These results suggest that Sp8 is a naturally processed epitope. We propose that Sp8 epitope should help in the characterization of mechanisms of virus control and immunopathology in SARS-CoV infection.",2009 Dec 3,"['Lv, Yanbo', 'Ruan, Zhihua', 'Wang, Li', 'Ni, Bing', 'Wu, Yuzhang']",BMC Immunol,,,True
98c1b2325128b3573b2793ba5d77dc07329c0195,PMC,Expression of the VP2 Protein of Murine Norovirus by a Translation Termination-Reinitiation Strategy,http://dx.doi.org/10.1371/journal.pone.0008390,PMC2793014,20027307,CC BY,"BACKGROUND: Expression of the minor virion structural protein VP2 of the calicivirus murine norovirus (MNV) is believed to occur by the unusual mechanism of termination codon-dependent reinitiation of translation. In this process, following translation of an upstream open reading frame (ORF) and termination at the stop codon, a proportion of 40S subunits remain associated with the mRNA and reinitiate at the AUG of a downstream ORF, which is typically in close proximity. Consistent with this, the VP2 start codon (AUG) of MNV overlaps the stop codon of the upstream VP1 ORF (UAA) in the pentanucleotide UAA UG. PRINCIPAL FINDINGS: Here, we confirm that MNV VP2 expression is regulated by termination-reinitiation and define the mRNA sequence requirements. Efficient reintiation is dependent upon 43 nt of RNA immediately upstream of the UAA UG site. Chemical and enzymatic probing revealed that the RNA in this region is not highly structured and includes an essential stretch of bases complementary to 18S rRNA helix 26 (Motif 1). The relative position of Motif 1 with respect to the UAA UG site impacts upon the efficiency of the process. Termination-reinitiation in MNV was also found to be relatively insensitive to the initiation inhibitor edeine. CONCLUSIONS: The termination-reinitiation signal of MNV most closely resembles that of influenza BM2. Similar to other viruses that use this strategy, base-pairing between mRNA and rRNA is likely to play a role in tethering the 40S subunit to the mRNA following termination at the VP1 stop codon. Our data also indicate that accurate recognition of the VP2 ORF AUG is not a pre-requisite for efficient reinitiation of translation in this system.",2009 Dec 22,"['Napthine, Sawsan', 'Lever, Robert A.', 'Powell, Michael L.', 'Jackson, Richard J.', 'Brown, T. David K.', 'Brierley, Ian']",PLoS One,,,True
99560951f295587952ccb543ccc8c214e6df62ae,PMC,"Genetics, Recombination and Clinical Features of Human Rhinovirus Species C (HRV-C) Infections; Interactions of HRV-C with Other Respiratory Viruses",http://dx.doi.org/10.1371/journal.pone.0008518,PMC2794544,20041158,CC0,"To estimate the frequency, molecular epidemiological and clinical associations of infection with the newly described species C variants of human rhinoviruses (HRV), 3243 diagnostic respiratory samples referred for diagnostic testing in Edinburgh were screened using a VP4-encoding region-based selective polymerase chain reaction (PCR) for HRV-C along with parallel PCR testing for 13 other respiratory viruses. HRV-C was the third most frequently detected behind respiratory syncytial virus (RSV) and adenovirus, with 141 infection episodes detected among 1885 subjects over 13 months (7.5%). Infections predominantly targeted the very young (median age 6–12 months; 80% of infections in those <2 years), occurred throughout the year but with peak incidence in early winter months. HRV-C was detected significantly more frequently among subjects with lower (LRT) and upper respiratory tract (URT) disease than controls without respiratory symptoms; HRV-C mono-infections were the second most frequently detected virus (behind RSV) in both disease presentations (6.9% and 7.8% of all cases respectively). HRV variants were classified by VP4/VP2 sequencing into 39 genotypically defined types, increasing the current total worldwide to 60. Through sequence comparisons of the 5′untranslated region (5′UTR), the majority grouped with species A (n = 96; 68%, described as HRV-Ca), the remainder forming a phylogenetically distinct 5′UTR group (HRV-Cc). Multiple and bidirectional recombination events between HRV-Ca and HRV-Cc variants and with HRV species A represents the most parsimonious explanation for their interspersed phylogeny relationships in the VP4/VP2-encoding region. No difference in age distribution, seasonality or disease associations was identified between HRV-Ca and HRV-Cc variants. HRV-C-infected subjects showed markedly reduced detection frequencies of RSV and other respiratory viruses, providing evidence for a major interfering effect of HRV-C on susceptibility to other respiratory virus infections. HRV-C's disease associations, its prevalence and evidence for interfering effects on other respiratory viruses mandates incorporation of rhinoviruses into future diagnostic virology screening.",2009 Dec 30,"['Wisdom, Anne', 'Kutkowska, Aldona E.', 'McWilliam Leitch, E. Carol', 'Gaunt, Eleanor', 'Templeton, Kate', 'Harvala, Heli', 'Simmonds, Peter']",PLoS One,,,True
73eb67835207270107c1e76b4675a92b3b58a575,PMC,Streptococcus pneumoniae Coinfection Is Correlated with the Severity of H1N1 Pandemic Influenza,http://dx.doi.org/10.1371/journal.pone.0008540,PMC2795195,20046873,CC BY,"BACKGROUND: Initial reports in May 2009 of the novel influenza strain H1N1pdm estimated a case fatality rate (CFR) of 0.6%, similar to that of seasonal influenza. In July 2009, however, Argentina reported 3056 cases with 137 deaths, representing a CFR of 4.5%. Potential explanations for increased CFR included virus reassortment or genetic drift, or infection of a more vulnerable population. Virus genomic sequencing of 26 Argentinian samples representing both severe and mild disease indicated no evidence of reassortment, mutations associated with resistance to antiviral drugs, or genetic drift that might contribute to virulence. Furthermore, no evidence was found for increased frequency of risk factors for H1N1pdm disease. METHODS/PRINCIPAL FINDINGS: We examined nasopharyngeal swab samples (NPS) from 199 cases of H1N1pdm infection from Argentina with MassTag PCR, testing for 33 additional microbial agents. The study population consisted of 199 H1N1pdm-infected subjects sampled between 23 June and 4 July 2009. Thirty-nine had severe disease defined as death (n = 20) or hospitalization (n = 19); 160 had mild disease. At least one additional agent of potential pathogenic importance was identified in 152 samples (76%), including Streptococcus pneumoniae (n = 62); Haemophilus influenzae (n = 104); human respiratory syncytial virus A (n = 11) and B (n = 1); human rhinovirus A (n = 1) and B (n = 4); human coronaviruses 229E (n = 1) and OC43 (n = 2); Klebsiella pneumoniae (n = 2); Acinetobacter baumannii (n = 2); Serratia marcescens (n = 1); and Staphylococcus aureus (n = 35) and methicillin-resistant S. aureus (MRSA, n = 6). The presence of S. pneumoniae was strongly correlated with severe disease. S. pneumoniae was present in 56.4% of severe cases versus 25% of mild cases; more than one-third of H1N1pdm NPS with S. pneumoniae were from subjects with severe disease (22 of 62 S. pneumoniae-positive NPS, p = 0.0004). In subjects 6 to 55 years of age, the adjusted odds ratio (OR) of severe disease in the presence of S. pneumoniae was 125.5 (95% confidence interval [CI], 16.95, 928.72; p<0.0001). CONCLUSIONS/SIGNIFICANCE: The association of S. pneumoniae with morbidity and mortality is established in the current and previous influenza pandemics. However, this study is the first to demonstrate the prognostic significance of non-invasive antemortem diagnosis of S. pneumoniae infection and may provide insights into clinical management.",2009 Dec 31,"['Palacios, Gustavo', 'Hornig, Mady', 'Cisterna, Daniel', 'Savji, Nazir', 'Bussetti, Ana Valeria', 'Kapoor, Vishal', 'Hui, Jeffrey', 'Tokarz, Rafal', 'Briese, Thomas', 'Baumeister, Elsa', 'Lipkin, W. Ian']",PLoS One,,,True
1b62107420aac57e1b7e2d496183036dec1ab905,PMC,Outdoor environments and human pathogens in air,http://dx.doi.org/10.1186/1476-069X-8-S1-S15,PMC2796493,20102582,CC BY,"Are pathogens in outdoor air a health issue at present or will they become a problem in the future? A working group called AirPath - Outdoor Environments and Human Pathogens in Air was set up in 2007 at University College London, UK with the aim of opening new discussion and creating a research network to investigate the science and impacts of outdoor pathogens. Our objective in this paper is to review and discuss the following areas: What is the source of human pathogens in outdoor air? What current, developing and future techniques do we need? Can we identify at-risk groups in relation to their activities and environments? How do we prepare for the anticipated challenges of environmental change and new and emerging diseases? And how can we control for and prevent pathogens in outdoor environments? We think that this work can benefit the wider research community and policy makers by providing a concise overview of various research aspects and considerations which may be important to their work.",2009 Dec 21,"['Lai, Ka man', 'Emberlin, Jean', 'Colbeck, Ian']",Environ Health,,,True
3a324b07dddba6a95b23d5cf90c4f0756b87afe4,PMC,"Let the sun shine in: effects of ultraviolet radiation on invasive pneumococcal disease risk in Philadelphia, Pennsylvania",http://dx.doi.org/10.1186/1471-2334-9-196,PMC2797517,19961583,CC BY,"BACKGROUND: Streptococcus pneumoniae is a common cause of community acquired pneumonia and bacteremia. Excess wintertime mortality related to pneumonia has been noted for over a century, but the seasonality of invasive pneumococcal disease (IPD) has been described relatively recently and is poorly understood. Improved understanding of environmental influence on disease seasonality has taken on new urgency due to global climate change. METHODS: We evaluated 602 cases of IPD reported in Philadelphia County, Pennsylvania, from 2002 to 2007. Poisson regression models incorporating seasonal smoothers were used to identify associations between weekly weather patterns and case counts. Associations between acute (day-to-day) environmental fluctuations and IPD occurrence were evaluated using a case-crossover approach. Effect modification across age and sex strata was explored, and meta-regression models were created using stratum-specific estimates for effect. RESULTS: IPD incidence was greatest in the wintertime, and spectral decomposition revealed a peak at 51.0 weeks, consistent with annual periodicity. After adjustment for seasonality, yearly increases in reporting, and temperature, weekly incidence was found to be associated with clear-sky UV index (IRR per unit increase in index: 0.70 [95% CI 0.54-0.91]). The effect of UV index was highest among young strata and decreased with age. At shorter time scales, only an association with increases in ambient sulphur oxides was linked to disease risk (OR for highest tertile of exposure 0.75, 95% CI 0.60 to 0.93). CONCLUSION: We confirmed the wintertime predominance of IPD in a major urban center. The major predictor of IPD in Philadelphia is extended periods of low UV radiation, which may explain observed wintertime seasonality. The mechanism of action of diminished light exposure on disease occurrence may be due to direct effects on pathogen survival or host immune function via altered 1,25-(OH)(2)-vitamin-D metabolism. These findings may suggest less diminution in future IPD risk with climate change than would be expected if wintertime seasonality was driven by temperature.",2009 Dec 4,"['White, Alexander NJ', 'Ng, Victoria', 'Spain, C Victor', 'Johnson, Caroline C', 'Kinlin, Laura M', 'Fisman, David N']",BMC Infect Dis,,,True
408c98fbba5d5584cc7fda96ec9b307d1cbd73bc,PMC,Recombinant porcine rotavirus VP4 and VP4-LTB expressed in Lactobacillus casei induced mucosal and systemic antibody responses in mice,http://dx.doi.org/10.1186/1471-2180-9-249,PMC2797526,19958557,CC BY,BACKGROUND: Porcine rotavirus infection is a significant cause of morbidity and mortality in the swine industry necessitating the development of effective vaccines for the prevention of infection. Immune responses associated with protection are primarily mucosal in nature and induction of mucosal immunity is important for preventing porcine rotavirus infection. RESULTS: Lactobacillus casei expressing the major protective antigen VP4 of porcine rotavirus (pPG612.1-VP4) or VP4-LTB (heat-labile toxin B subunit from Echerichia coli) (pPG612.1-VP4-LTB) fusion protein was used to immunize mice orally. The expression of recombinant pPG612.1-VP4 and pPG612.1-VP4-LTB was confirmed by SDS-PAGE and Western blot analysis and surface-displayed expression on L. casei was verified by immunofluorescence. Mice orally immunized with recombinant protein-expressing L. casei produced high levels of serum immunoglobulin G (IgG) and mucosal IgA. The IgA titters from mice immunized with pPG612.1-VP4-LTB were higher than titters from pPG612.1-VP4-immunized mice. The induced antibodies demonstrated neutralizing effects on RV infection. CONCLUSION: These results demonstrated that VP4 administered in the context of an L. casei expression system is an effective method for stimulating mucosal immunity and that LTB served to further stimulate mucosal immunity suggesting that this strategy can be adapted for use in pigs.,2009 Dec 4,"['Qiao, Xinyuan', 'Li, Guiwei', 'Wang, Xiangqing', 'Li, Xiaojing', 'Liu, Min', 'Li, Yijing']",BMC Microbiol,,,True
89dc30e7b46b476142978f461feb4ecca1bf89b7,PMC,Listeriolysin O Is Necessary and Sufficient to Induce Autophagy during Listeria monocytogenes Infection,http://dx.doi.org/10.1371/journal.pone.0008610,PMC2797616,20062534,CC BY,"BACKGROUND: Recent studies have suggested that autophagy is utilized by cells as a protective mechanism against Listeria monocytogenes infection. METHODOLOGY/PRINCIPAL FINDINGS: However we find autophagy has no measurable role in vacuolar escape and intracellular growth in primary cultured bone marrow derived macrophages (BMDMs) deficient for autophagy (atg5(−/−)). Nevertheless, we provide evidence that the pore forming activity of the cholesterol-dependent cytolysin listeriolysin O (LLO) can induce autophagy subsequent to infection by L. monocytogenes. Infection of BMDMs with L. monocytogenes induced microtubule-associated protein light chain 3 (LC3) lipidation, consistent with autophagy activation, whereas a mutant lacking LLO did not. Infection of BMDMs that express LC3-GFP demonstrated that wild-type L. monocytogenes was encapsulated by LC3-GFP, consistent with autophagy activation, whereas a mutant lacking LLO was not. Bacillus subtilis expressing either LLO or a related cytolysin, perfringolysin O (PFO), induced LC3 colocalization and LC3 lipidation. Further, LLO-containing liposomes also recruited LC3-GFP, indicating that LLO was sufficient to induce targeted autophagy in the absence of infection. The role of autophagy had variable effects depending on the cell type assayed. In atg5(−/−) mouse embryonic fibroblasts, L. monocytogenes had a primary vacuole escape defect. However, the bacteria escaped and grew normally in atg5(−/−) BMDMs. CONCLUSIONS/SIGNIFICANCE: We propose that membrane damage, such as that caused by LLO, triggers bacterial-targeted autophagy, although autophagy does not affect the fate of wild-type intracellular L. monocytogenes in primary BMDMs.",2010 Jan 6,"['Meyer-Morse, Nicole', 'Robbins, Jennifer R.', 'Rae, Chris S.', 'Mochegova, Sofia N.', 'Swanson, Michele S.', 'Zhao, Zijiang', 'Virgin, Herbert W.', 'Portnoy, Daniel']",PLoS One,,,True
5ab2ff8df3b1bc8a71ab66025f5dcee729242583,PMC,Intracranial Administration of P Gene siRNA Protects Mice from Lethal Chandipura Virus Encephalitis,http://dx.doi.org/10.1371/journal.pone.0008615,PMC2797643,20062542,CC BY,"BACKGROUND: In parts of India, Chandipura Virus (CHPV) has emerged as an encephalitis causing pathogen in both epidemic and sporadic forms. This pediatric disease follows rapid course leading to 55–75% mortality. In the absence of specific treatment, effectiveness of RNA interference (RNAi) was evaluated. METHODS AND FINDINGS: Efficacy of synthetic short interfering RNA (siRNA) or short hairpin RNA (shRNA) in protecting mice from CHPV infection was assessed. The target genes were P and M genes primarily because important role of the former in viral replication and lethal nature of the latter. Real time one step RT-PCR and plaque assay were used for the assessment of gene silencing. Using pAcGFP1N1-CHPV-P, we showed that P-2 siRNA was most efficient in reducing the expression of P gene in-vitro. Both quantitative assays documented 2logs reduction in the virus titer when P-2, M-5 or M-6 siRNAs were transfected 2hr post infection (PI). Use of these siRNAs in combination did not result in enhanced efficiency. P-2 siRNA was found to tolerate four mismatches in the center. As compared to five different shRNAs, P-2 siRNA was most effective in inhibiting CHPV replication. An extended survival was noted when mice infected intracranially with 100 LD(50) CHPV were treated with cationic lipid complexed 5 µg P-2 siRNA simultaneously. Infection with 10LD(50) and treatment with two doses of siRNA first, simultaneously and second 24 hr PI, resulted in 70% survival. Surviving mice showed 4logs less CHPV titers in brain without histopathological changes or antibody response. Gene expression profiles of P-2 siRNA treated mice showed no interferon response. First dose of siRNA at 2hr or 4hr PI with second dose at 24hr resulted in 40% and 20% survival respectively suggesting potential application in therapy. CONCLUSIONS: The results highlight therapeutic potential of siRNA in treating rapid and fatal Chandipura encephalitis.",2010 Jan 7,"['Kumar, Satyendra', 'Arankalle, Vidya A.']",PLoS One,,,True
d55f09671ad483ed5c25dbff97c970e08c6be947,PMC,The neck-region polymorphism of DC-SIGNR in peri-centenarian from Han Chinese Population,http://dx.doi.org/10.1186/1471-2350-10-134,PMC2797785,20003397,CC BY,"BACKGROUND: DC-SIGNR (also called CD209L) has been extensively studied on its role in host genetic predisposition to viral infection. In particular, variable number tandem repeat (VNTR) of the neck-region of DC-SIGNR is highly polymorphic and the polymorphism has been investigated for genetic predisposition to various infectious diseases, though conflicting results had been reported. As infection is a major cause of human death and a mechanism of natural selection, we hypothesized that VNTR polymorphism of DC-SIGNR might have an effect on human life span. METHODS: Here we collected 361 peri-centenarian individuals (age ≥94 for female and age ≥90 for male) and 342 geographically matched controls (age 22-53, mean 35.0 ± 12.0) from Han Chinese. The VNTR polymorphism of the neck region was determined by PCR and genotype was called by separating the PCR products in agarose gel. RESULTS: A total of 11 genotypes and 5 alleles were found in our population. The genotype distribution, allele frequencies and homozygote proportion did not show a significant difference between peri-centenarian and control group. As gender differences in lifespan are ubiquitously observed throughout the animal kingdom, we then stratified the samples by gender. There was more 6/7 genotypes in female peri-centenarian group than that in female control group, at a marginal level of significance (5.56 vs. 1.28%, p = 0.041). The difference was not significant after correction by Bonferroni method. It suggests a possible differential effect of DC-SIGNR VNTR genotypes between sexes. Further studies are warranted to confirm our preliminary findings and investigate the mechanisms of the underlying functions. CONCLUSIONS: Our study indicated that there was absence of association between the neck region polymorphism of DC-SIGNR and longevity in Han Chinese population. But the question of whether the DC-SIGNR could affect longevity in a gender-specific pattern remains open.",2009 Dec 14,"['Li, Hui', 'Wang, Cheng-Ye', 'Wang, Jia-Xin', 'Tang, Nelson Leung-Sang', 'Xie, Liang', 'Gong, Yuan-Ying', 'Yang, Zhao', 'Xu, Liang-You', 'Kong, Qing-Peng', 'Zhang, Ya-Ping']",BMC Med Genet,,,True
55cc676ae1d05bf9cacceacd765846abfeae92a9,PMC,Translational Studies of Alcoholism: Bridging the Gap,,PMC2798743,20041042,CC0,"Human studies are necessary to identify and classify the brain systems predisposing individuals to develop alcohol use disorders and those modified by alcohol, while animal models of alcoholism are essential for a mechanistic understanding of how chronic voluntary alcohol consumption becomes compulsive, how brain systems become damaged, and how damage resolves. Our current knowledge of the neuroscience of alcohol dependence has evolved from the interchange of information gathered from both human alcoholics and animal models of alcoholism. Together, studies in humans and animal models have provided support for the involvement of specific brain structures over the course of alcohol addiction, including the prefrontal cortex, basal ganglia, cerebellum, amygdala, hippocampus, and the hypothalamic–pituitary–adrenal axis.",2008,"['Zahr, Natalie M.', 'Sullivan, Edith V.']",Alcohol Res Health,,,True
73af6e73949ec28b7c3b13d24a9168e891d7bb23,PMC,Developing 21(st )century accreditation standards for teaching hospitals: the Taiwan experience,http://dx.doi.org/10.1186/1472-6963-9-232,PMC2801490,20003505,CC BY,"BACKGROUND: The purpose of this study is to establish teaching hospital accreditation standards anew with the hope that Taiwan's teaching hospitals can live up to the expectations of our society and ensure quality teaching. METHODS: The development process lasted two years, 2005-2006, and was separated into three stages. The first stage centered on leadership meetings and consensus building, the second on drafting the new standards with expert focus groups, and the third on a pilot study and subsequent revision. RESULTS: Our new teaching hospital accreditation standards have six categories and 95 standards as follows: educational resources (20 items), teaching and training plans and outcomes (42 items), research and results (9 items), development of clinical faculty and continuing education (8 items), academic exchanges and community education (8 items), and administration (8 items). CONCLUSIONS: The new standards have proven feasible and posed reasonable challenges in the pilot study. We hope the new standards will strengthen teaching and research, and improve the quality of hospital services at the same time.",2009 Dec 15,"['Huang, Chung-I', 'Wung, Cathy', 'Yang, Che-Ming']",BMC Health Serv Res,,,True
0f3fae76f66b8f351abbef071fdf7e6efc1c325c,PMC,Development of a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) system for a highly sensitive detection of enterovirus in the stool samples of acute flaccid paralysis cases,http://dx.doi.org/10.1186/1471-2334-9-208,PMC2803793,20015403,CC BY,"BACKGROUND: In the global eradication program for poliomyelitis, the laboratory diagnosis plays a critical role by isolating poliovirus (PV) from the stool samples of acute flaccid paralysis (AFP) cases. In this study, we developed a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) system for a rapid and highly sensitive detection of enterovirus including PV to identify stool samples positive for enterovirus including PV. METHODS: A primer set was designed for RT-LAMP to detect enterovirus preferably those with PV-like 5'NTRs of the viral genome. The sensitivity of RT-LAMP system was evaluated with prototype strains of enterovirus. Detection of enterovirus from stool extracts was examined by using RT-LAMP system. RESULTS: We detected at least 400 copies of the viral genomes of PV(Sabin) strains within 90 min by RT-LAMP with the primer set. This RT-LAMP system showed a preference for Human enterovirus species C (HEV-C) strains including PV, but exhibited less sensitivity to the prototype strains of HEV-A and HEV-B (detection limits of 7,400 to 28,000 copies). Stool extracts, from which PV, HEV-C, or HEV-A was isolated in the cell culture system, were mostly positive by RT-LAMP method (positive rates of 15/16 (= 94%), 13/14 (= 93%), and 4/4 (= 100%), respectively). The positive rate of this RT-LAMP system for stool extracts from which HEV-B was isolated was lower than that of HEV-C (positive rate of 11/21 (= 52%)). In the stool samples, which were negative for enterovirus isolation by the cell culture system, we found that two samples were positive for RT-LAMP (positive rates of 2/38 (= 5.3%)). In these samples, enterovirus 96 was identified by sequence analysis utilizing a seminested PCR system. CONCLUSIONS: RT-LAMP system developed in this study showed a high sensitivity comparable to that of the cell culture system for the detection of PV, HEV-A, and HEV-C, but less sensitivity to HEV-B. This RT-LAMP system would be useful for the direct detection of enterovirus from the stool extracts.",2009 Dec 16,"['Arita, Minetaro', 'Ling, Hua', 'Yan, Dongmei', 'Nishimura, Yorihiro', 'Yoshida, Hiromu', 'Wakita, Takaji', 'Shimizu, Hiroyuki']",BMC Infect Dis,,,True
53003a256222203353a3aec2be3ada210544775f,PMC,Diagnosis of Parasitic Diseases: Old and New Approaches,http://dx.doi.org/10.1155/2009/278246,PMC2804041,20069111,CC BY,"Methods for the diagnosis of infectious diseases have stagnated in the last 20–30 years. Few major advances in clinical diagnostic testing have been made since the introduction of PCR, although new technologies are being investigated. Many tests that form the backbone of the “modern” microbiology laboratory are based on very old and labour-intensive technologies such as microscopy for malaria. Pressing needs include more rapid tests without sacrificing sensitivity, value-added tests, and point-of-care tests for both high- and low-resource settings. In recent years, research has been focused on alternative methods to improve the diagnosis of parasitic diseases. These include immunoassays, molecular-based approaches, and proteomics using mass spectrometry platforms technology. This review summarizes the progress in new approaches in parasite diagnosis and discusses some of the merits and disadvantages of these tests.",2009 Dec 30,"Ndao, Momar",Interdiscip Perspect Infect Dis,,,True
5e8669392733113d4bbaeebd9347764807872fa2,PMC,Prophylactic and therapeutic activity of fully human monoclonal antibodies directed against Influenza A M2 protein,http://dx.doi.org/10.1186/1743-422X-6-224,PMC2804611,20025741,CC BY,"Influenza virus infection is a prevalent disease in humans. Antibodies against hemagglutinin have been shown to prevent infection and hence hemagglutinin is the major constituent of current vaccines. Antibodies directed against the highly conserved extracellular domain of M2 have also been shown to mediate protection against Influenza A infection in various animal models. Active vaccination is generally considered the best approach to combat viral diseases. However, passive immunization is an attractive alternative, particularly in acutely exposed or immune compromized individuals, young children and the elderly. We recently described a novel method for the rapid isolation of natural human antibodies by mammalian cell display. Here we used this approach to isolate human monoclonal antibodies directed against the highly conserved extracellular domain of the Influenza A M2 protein. The identified antibodies bound M2 peptide with high affinities, recognized native cell-surface expressed M2 and protected mice from a lethal influenza virus challenge. Moreover, therapeutic treatment up to 2 days after infection was effective, suggesting that M2-specific monoclonals have a great potential as immunotherapeutic agents against Influenza infection.",2009 Dec 21,"['Beerli, Roger R', 'Bauer, Monika', 'Schmitz, Nicole', 'Buser, Regula B', 'Gwerder, Myriam', 'Muntwiler, Simone', 'Renner, Wolfgang A', 'Saudan, Philippe', 'Bachmann, Martin F']",Virol J,,,True
c6e819e9d3fdfd19cafd2ddf160b9ed2cfd9a27a,PMC,Public perceptions of quarantine: community-based telephone survey following an infectious disease outbreak,http://dx.doi.org/10.1186/1471-2458-9-470,PMC2804616,20015400,CC BY,"BACKGROUND: The use of restrictive measures such as quarantine draws into sharp relief the dynamic interplay between the individual rights of the citizen on the one hand and the collective rights of the community on the other. Concerns regarding infectious disease outbreaks (SARS, pandemic influenza) have intensified the need to understand public perceptions of quarantine and other social distancing measures. METHODS: We conducted a telephone survey of the general population in the Greater Toronto Area in Ontario, Canada. Computer-assisted telephone interviewing (CATI) technology was used. A final sample of 500 individuals was achieved through standard random-digit dialing. RESULTS: Our data indicate strong public support for the use of quarantine when required and for serious legal sanctions against those who fail to comply. This support is contingent both on the implementation of legal safeguards to protect against inappropriate use and on the provision of psychosocial supports for those affected. CONCLUSION: To engender strong public support for quarantine and other restrictive measures, government officials and public health policy-makers would do well to implement a comprehensive system of supports and safeguards, to educate and inform frontline public health workers, and to engage the public at large in an open dialogue on the ethical use of restrictive measures during infectious disease outbreaks.",2009 Dec 16,"['Tracy, C Shawn', 'Rea, Elizabeth', 'Upshur, Ross EG']",BMC Public Health,,,True
f6ed1f1e9999e57793addb1c9c54f61c7861a995,PMC,A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1,http://dx.doi.org/10.1186/1471-2172-10-64,PMC2804704,20017901,CC BY,"BACKGROUND: Mycobacterium tuberculosis (MTB) is a major cause of morbidity and mortality in the world. To combat against this pathogen, immune cells release cytokines including tumor necrosis factor-α (TNF-α), which is pivotal in the development of protective granulomas. Our previous results showed that Bacillus Calmette Guerin (BCG), a mycobacterium used as a model to investigate the immune response against MTB, stimulates the induction of TNF-α via mitogen-activated protein kinase (MAPK) in human blood monocytes. Since MAPK phosphatase-1 (MKP-1) is known to regulate MAPK activities, we examined whether MKP-1 plays a role in BCG-induced MAPK activation and cytokine expression. RESULTS: Primary human blood monocytes were treated with BCG and assayed for MKP-1 expression. Our results demonstrated that following exposure to BCG, there was an increase in the expression of MKP-1. Additionally, the induction of MKP-1 was regulated by p38 MAPK and extracellular signal-regulated kinase 1 and 2 (ERK1/2). Surprisingly, when MKP-1 expression was blocked by its specific siRNA, there was a significant decrease in the levels of phospho-MAPK (p38 MAPK and ERK1/2) and TNF-α inducible by BCG. CONCLUSIONS: Since TNF-α is pivotal in granuloma formation, the results indicated an unexpected positive function of MKP-1 against mycobacterial infection as opposed to its usual phosphatase activity.",2009 Dec 17,"['Cheung, Benny KW', 'Yim, Howard CH', 'Lee, Norris CM', 'Lau, Allan SY']",BMC Immunol,,,True
331d9c08ce93e1ca8843610514f7ecb1d83dd883,PMC,Mutagenesis of the transmembrane domain of the SARS coronavirus spike glycoprotein: refinement of the requirements for SARS coronavirus cell entry,http://dx.doi.org/10.1186/1743-422X-6-230,PMC2805634,20034394,CC BY,"BACKGROUND: The spike protein (S) of SARS Coronavirus (SARS-CoV) mediates entry of the virus into target cells, including receptor binding and membrane fusion. Close to or in the viral membrane, the S protein contains three distinct motifs: a juxtamembrane aromatic part, a central highly hydrophobic stretch and a cysteine rich motif. Here, we investigate the role of aromatic and hydrophobic parts of S in the entry of SARS CoV and in cell-cell fusion. This was investigated using the previously described SARS pseudotyped particles system (SARSpp) and by fluorescence-based cell-cell fusion assays. RESULTS: Mutagenesis showed that the aromatic domain was crucial for SARSpp entry into cells, with a likely role in pore enlargement. Introduction of lysine residues in the hydrophobic stretch of S also resulted in a block of entry, suggesting the borders of the actual transmembrane domain. Surprisingly, replacement of a glycine residue, situated close to the aromatic domain, with a lysine residue was tolerated, whereas the introduction of a lysine adjacent to the glycine, was not. In a model, we propose that during fusion, the lateral flexibility of the transmembrane domain plays a critical role, as do the tryptophans and the cysteines. CONCLUSIONS: The aromatic domain plays a crucial role in the entry of SARS CoV into target cells. The positioning of the aromatic domain and the hydrophobic domain relative to each other is another essential characteristic of this membrane fusion process.",2009 Dec 24,"['Corver, Jeroen', 'Broer, Rene', 'van Kasteren, Puck', 'Spaan, Willy']",Virol J,,,True
ecf15cf19a780b1f9e58e9a5b35402ca5886adab,PMC,EBNA3C interacts with Gadd34 and counteracts the unfolded protein response,http://dx.doi.org/10.1186/1743-422X-6-231,PMC2805635,20040105,CC BY,"EBNA3C is an EBV-encoded nuclear protein, essential for proliferation of EBV infected B-lymphocytes. Using EBNA3C amino acids 365-545 in a yeast two hybrid screen, we found an interaction with the Growth Arrest and DNA-damage protein, Gadd34. When both proteins are overexpressed, Gadd34 can interact with EBNA3C in both nuclear and cytoplasmic compartments. Amino acids 483-610 of Gadd34, including the two PP1a interaction, and the HSV-1 ICPγ34.5 homology domains, are required for the interaction. Furthermore, interaction is lost with a mutant of EBNA3C ((509 )DVIEVID (515)→AVIAVIA), that abolishes EBNA3C coactivation ability as well as SUMO interaction[1]. In B-cells, Gadd34, and EBNA3C are present in a complex with PP1a using microcystin sepharose affinity purification, Using a lymphoblastoid cell line in which EBNA3C protein levels are conditional on hydroxytamoxifen, surprisingly, we found that (i) EBNA3C maintains phosphorylation of eIF2α at serine 51, and (ii) protects against ER stress induced activation of the unfolded protein response as measured by XBP1 (u) versus XBP1(s) protein expression and N-terminal ATF6 cleavage. In reporter assays, overexpression of Gadd34 enhances EBNA3C's ability to co-activate EBNA2 activation of the LMP1 promoter. Collectively the data suggest that EBNA3C interacts with Gadd34, activating the upstream component of the UPR (eIF2α phosphorylation) while preventing downstream UPR events (XBP1 activation and ATF6 cleavage).",2009 Dec 29,"['Garrido, Jose L', 'Maruo, Seijii', 'Takada, Kenzo', 'Rosendorff, Adam']",Virol J,,,True
b4e5ee4be574a65dee1c7fca178580f9db58087f,PMC,Global Expression Profiling in Epileptogenesis: Does It Add to the Confusion?,http://dx.doi.org/10.1111/j.1750-3639.2008.00254.x,PMC2805866,19243383,CC BY,"Since the inception of global gene expression profiling platforms in the mid-1990s, there has been a significant increase in publications of differentially expressed genes in the process of epileptogenesis. In particular for mesial temporal lobe epilepsy, the presence of a latency period between the first manifestation of seizures to chronic epilepsy provides the opportunity for therapeutic interventions at the molecular biology level. Using global expression profiling techniques, approximately 2000 genes have been published demonstrating differential expression in mesial temporal epilepsy. The majority of these changes, however, are specific to laboratory or experimental conditions with only 53 genes demonstrating changes in more than two publications. To this end, we review the current status of gene expression profiling in epileptogenesis and suggest standard guidelines to be followed for greater accuracy and reproducibility of results.",2010 Jan,"['Wang, Yi Yuen', 'Smith, Paul', 'Murphy, Michael', 'Cook, Mark']",Brain Pathol,,,True
a8b801f23efa409e89226176fec4c0517e330717,PMC,Linking mechanistic and behavioral responses to sublethal esfenvalerate exposure in the endangered delta smelt; Hypomesus transpacificus (Fam. Osmeridae),http://dx.doi.org/10.1186/1471-2164-10-608,PMC2806348,20003521,CC BY,"BACKGROUND: The delta smelt (Hypomesus transpacificus) is a pelagic fish species listed as endangered under both the USA Federal and Californian State Endangered Species Acts and considered an indicator of ecosystem health in its habitat range, which is limited to the Sacramento-San Joaquin estuary in California, USA. Anthropogenic contaminants are one of multiple stressors affecting this system, and among them, current-use insecticides are of major concern. Interrogative tools are required to successfully monitor effects of contaminants on the delta smelt, and to research potential causes of population decline in this species. We have created a microarray to investigate genome-wide effects of potentially causative stressors, and applied this tool to assess effects of the pyrethroid insecticide esfenvalerate on larval delta smelt. Selected genes were further investigated as molecular biomarkers using quantitative PCR analyses. RESULTS: Exposure to esfenvalerate affected swimming behavior of larval delta smelt at concentrations as low as 0.0625 μg.L(-1), and significant differences in expression were measured in genes involved in neuromuscular activity. Alterations in the expression of genes associated with immune responses, along with apoptosis, redox, osmotic stress, detoxification, and growth and development appear to have been invoked by esfenvalerate exposure. Swimming impairment correlated significantly with expression of aspartoacylase (ASPA), an enzyme involved in brain cell function and associated with numerous human diseases. Selected genes were investigated for their use as molecular biomarkers, and strong links were determined between measured downregulation in ASPA and observed behavioral responses in fish exposed to environmentally relevant pyrethroid concentrations. CONCLUSIONS: The results of this study show that microarray technology is a useful approach in screening for, and generation of molecular biomarkers in endangered, non-model organisms, identifying specific genes that can be directly linked with sublethal toxicological endpoints; such as changes in expression levels of neuromuscular genes resulting in measurable swimming impairments. The developed microarrays were successfully applied on larval fish exposed to esfenvalerate, a known contaminant of the Sacramento-San Joaquin estuary, and has permitted the identification of specific biomarkers which could provide insight into the factors contributing to delta smelt population decline.",2009 Dec 15,"['Connon, Richard E', 'Geist, Juergen', 'Pfeiff, Janice', 'Loguinov, Alexander V', ""D'Abronzo, Leandro S"", 'Wintz, Henri', 'Vulpe, Christopher D', 'Werner, Inge']",BMC Genomics,,,True
87a937ec2cd698b7d24ade1803a22852747ec8c7,PMC,Efficacy and safety of 2-hour urokinase regime in acute pulmonary embolism: a randomized controlled trial,http://dx.doi.org/10.1186/1465-9921-10-128,PMC2806365,20040086,CC BY,"BACKGROUNDS: Urokinase (UK) 2 200 U/kg·h for 12 hours infusion(UK-12 h)is an ACCP recommended regimen in treating acute pulmonary embolism (PE). It is unclear whether this dose and time can be reduced further. We compared the efficacy and safety of 20, 000 U/kg for 2 hours (UK-2 h) with the UK-12 h regime in selected PE patients. METHODS: A randomized trial involving 129 patients was conducted. Patients with acute PE were randomly assigned to receive either UK-12 h (n = 70), or UK-2 h (n = 59). The efficacy was determined by the improvement of right heart dysfunction and perfusion defect at 24 h and 14 d post UK treatment. The bleeding incidence, death rate and PE recurrence were also evaluated. RESULTS: Similarly significant improvements in right heart dysfunction and lung perfusion defects were observed in both groups. Overall bleeding incidents were low in both groups. Major bleeding directly associated with UK infusion occurred in one patient in the UK-2 h group and one in the UK-12 h group. Mortality rates were low, with one reported fatal recurrent in the UK-12 h group and none in the UK-2 h group. When the rate of bleeding, death and PE recurrence were compared separately in the hemodynamic instability and the massive anatomic obstruction subgroups, no significant difference was found. CONCLUSIONS: The UK-2 h regimen exhibits similar efficacy and safety as the UK-12 h regimen for acute PE. TRIAL REGISTRATION: Clinical trial registered with http://clinicaltrials.gov/ct2/show/NCT00799968 (Identifier: NCT 00799968)",2009 Dec 29,"['Wang, Chen', 'Zhai, Zhenguo', 'Yang, Yuanhua', 'Yuan, Yadong', 'Cheng, Zhaozhong', 'Liang, Lirong', 'Dai, Huaping', 'Huang, Kewu', 'Lu, Weixuan', 'Zhang, Zhonghe', 'Cheng, Xiansheng', 'Shen, Ying H', None]",Respir Res,,,True
8f5fc8690f47c0c30dd99bd8d84f9e80f25fdcc8,PMC,Influenza H5N1 and H1N1 Virus Replication and Innate Immune Responses in Bronchial Epithelial Cells Are Influenced by the State of Differentiation,http://dx.doi.org/10.1371/journal.pone.0008713,PMC2806912,20090947,CC BY,"Influenza H5N1 virus continues to be enzootic in poultry and transmits zoonotically to humans. Although a swine-origin H1N1 virus has emerged to become pandemic, its virulence for humans remains modest in comparison to that seen in zoonotic H5N1 disease. As human respiratory epithelium is the primary target cells for influenza viruses, elucidating the viral tropism and host innate immune responses of influenza H5N1 virus in human bronchial epithelium may help to understand the pathogenesis. Here we established primary culture of undifferentiated and well differentiated normal human bronchial epithelial (NHBE) cells and infected with highly pathogenic influenza H5N1 virus (A/Vietnam/3046/2004) and a seasonal influenza H1N1 virus (A/Hong Kong/54/1998), the viral replication kinetics and cytokine and chemokine responses were compared by qPCR and ELISA. We found that the in vitro culture of the well differentiated NHBE cells acquired the physiological properties of normal human bronchi tissue which express high level of α2-6-linked sialic acid receptors and human airway trypsin-like (HAT) protease, in contrast to the low expression in the non-differentiated NHBE cells. When compared to H1N1 virus, the H5N1 virus replicated more efficiently and induced a stronger type I interferon response in the undifferentiated NHBE cells. In contrast, in well differentiated cultures, H5N1 virus replication was less efficient and elicited a lower interferon-beta response in comparison with H1N1 virus. Our data suggest that the differentiation of bronchial epithelial cells has a major influence in cells' permissiveness to human H1N1 and avian H5N1 viruses and the host innate immune responses. The reduced virus replication efficiency partially accounts for the lower interferon-beta responses in influenza H5N1 virus infected well differentiated NHBE cells. Since influenza infection in the bronchial epithelium will lead to tissue damage and associate with the epithelium regeneration, the data generated from the undifferentiated NHBE cultures may also be relevant to disease pathogenesis.",2010 Jan 15,"['Chan, Renee W. Y.', 'Yuen, Kit M.', 'Yu, Wendy C. L.', 'Ho, Carol C. C.', 'Nicholls, John M.', 'Peiris, J. S. Malik', 'Chan, Michael C. W.']",PLoS One,,,True
0e23b62f7dca85c31f4f90603d2a28dfc7177947,PMC,Dynamic Innate Immune Responses of Human Bronchial Epithelial Cells to Severe Acute Respiratory Syndrome-Associated Coronavirus Infection,http://dx.doi.org/10.1371/journal.pone.0008729,PMC2806919,20090954,CC BY,"Human lung epithelial cells are likely among the first targets to encounter invading severe acute respiratory syndrome-associated coronavirus (SARS-CoV). Not only can these cells support the growth of SARS-CoV infection, but they are also capable of secreting inflammatory cytokines to initiate and, eventually, aggravate host innate inflammatory responses, causing detrimental immune-mediated pathology within the lungs. Thus, a comprehensive evaluation of the complex epithelial signaling to SARS-CoV is crucial for paving the way to better understand SARS pathogenesis. Based on microarray-based functional genomics, we report here the global gene response of 2B4 cells, a cloned bronchial epithelial cell line derived from Calu-3 cells. Specifically, we found a temporal and spatial activation of nuclear factor (NF)κB, activator protein (AP)-1, and interferon regulatory factor (IRF)-3/7 in infected 2B4 cells at 12-, 24-, and 48-hrs post infection (p.i.), resulting in the activation of many antiviral genes, including interferon (IFN)-β, -λs, inflammatory mediators, and many IFN-stimulated genes (ISGs). We also showed, for the first time, that IFN-β and IFN-λs were capable of exerting previously unrecognized, non-redundant, and complementary abilities to limit SARS-CoV replication, even though their expression could not be detected in infected 2B4 bronchial epithelial cells until 48 hrs p.i. Collectively, our results highlight the mechanics of the sequential events of antiviral signaling pathway/s triggered by SARS-CoV in bronchial epithelial cells and identify novel cellular targets for future studies, aiming at advancing strategies against SARS.",2010 Jan 15,"['Yoshikawa, Tomoki', 'Hill, Terence E.', 'Yoshikawa, Naoko', 'Popov, Vsevolod L.', 'Galindo, Cristi L.', 'Garner, Harold R.', 'Peters, C. J.', 'Tseng, Chien-Te (Kent)']",PLoS One,,,True
31b6292728805572de28133c6eb02ed1d44ef211,PMC,Automated Detection of Conformational Epitopes Using Phage Display Peptide Sequences,,PMC2808184,20140073,CC BY,"BACKGROUND: Precise determination of conformational epitopes of neutralizing antibodies represents a key step in the rational design of novel vaccines. A powerful experimental method to gain insights on the physical chemical nature of conformational epitopes is the selection of linear peptides that bind with high affinities to a monoclonal antibody of interest by phage display technology. However, the structural characterization of conformational epitopes from these mimotopes is not straightforward, and in the past the interpretation of peptide sequences from phage display experiments focused on linear sequence analysis to find a consensus sequence or common sequence motifs. RESULTS: We present a fully automated search method, EpiSearch that predicts the possible location of conformational epitopes on the surface of an antigen. The algorithm uses peptide sequences from phage display experiments as input, and ranks all surface exposed patches according to the frequency distribution of similar residues in the peptides and in the patch. We have tested the performance of the EpiSearch algorithm for six experimental data sets of phage display experiments, the human epidermal growth factor receptor-2 (HER-2/neu), the antibody mAb Bo2C11 targeting the C(2) domain of FVIII, antibodies mAb 17b and mAb b12 of the HIV envelope protein gp120, mAb 13b5 targeting HIV-1 capsid protein and 80R of the SARS coronavirus spike protein. In all these examples the conformational epitopes as determined by the X-ray crystal structures of the antibody-antigen complexes, were found within the highest scoring patches of EpiSearch, covering in most cases more than 50% residues of experimental observed conformational epitopes. Input options of the program include mapping of a single peptide or a set of peptides on the antigen structure, and the results of the calculation can be visualized on our interactive web server. AVAILABILITY: Users can access the EpiSearch from our web server http://curie.utmb.edu/episearch.html",2009 Jul 1,"['Negi, Surendra S', 'Braun, Werner']",Bioinform Biol Insights,,,True
7a4c5c15a8bbf8fdb5694b2ce8aaf72991784476,PMC,Quantifying the impact of community quarantine on SARS transmission in Ontario: estimation of secondary case count difference and number needed to quarantine,http://dx.doi.org/10.1186/1471-2458-9-488,PMC2808319,20034405,CC BY,"BACKGROUND: Community quarantine is controversial, and the decision to use and prepare for it should be informed by specific quantitative evidence of benefit. Case-study reports on 2002-2004 SARS outbreaks have discussed the role of quarantine in the community in transmission. However, this literature has not yielded quantitative estimates of the reduction in secondary cases attributable to quarantine as would be seen in other areas of health policy and cost-effectiveness analysis. METHODS: Using data from the 2003 Ontario, Canada, SARS outbreak, two novel expressions for the impact of quarantine are presented. Secondary Case Count Difference (SCCD) reflects reduction in the average number of transmissions arising from a SARS case in quarantine, relative to not in quarantine, at onset of symptoms. SCCD was estimated using Poisson and negative binomial regression models (with identity link function) comparing the number of secondary cases to each index case for quarantine relative to non-quarantined index cases. The inverse of this statistic is proposed as the number needed to quarantine (NNQ) to prevent one additional secondary transmission. RESULTS: Our estimated SCCD was 0.133 fewer secondary cases per quarantined versus non-quarantined index case; and a NNQ of 7.5 exposed individuals to be placed in community quarantine to prevent one additional case of transmission in the community. This analysis suggests quarantine can be an effective preventive measure, although these estimates lack statistical precision. CONCLUSIONS: Relative to other health policy areas, literature on quarantine tends to lack in quantitative expressions of effectiveness, or agreement on how best to report differences in outcomes attributable to control measure. We hope to further this discussion through presentation of means to calculate and express the impact of population control measures. The study of quarantine effectiveness presents several methodological and statistical challenges. Further research and discussion are needed to understand the costs and benefits of enacting quarantine, and this includes a discussion of how quantitative benefit should be communicated to decision-makers and the public, and evaluated.",2009 Dec 24,"['Bondy, Susan J', 'Russell, Margaret L', 'Laflèche, Julie ML', 'Rea, Elizabeth']",BMC Public Health,,,True
88d360849c4d9dddb7c9d16db3e9c4bbb52b7b75,PMC,Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals,http://dx.doi.org/10.1371/journal.pone.0008805,PMC2808385,20098712,CC BY,"BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.",2010 Jan 20,"['Corti, Davide', 'Langedijk, Johannes P. M.', 'Hinz, Andreas', 'Seaman, Michael S.', 'Vanzetta, Fabrizia', 'Fernandez-Rodriguez, Blanca M.', 'Silacci, Chiara', 'Pinna, Debora', 'Jarrossay, David', 'Balla-Jhagjhoorsingh, Sunita', 'Willems, Betty', 'Zekveld, Maria J.', 'Dreja, Hanna', ""O'Sullivan, Eithne"", 'Pade, Corinna', 'Orkin, Chloe', 'Jeffs, Simon A.', 'Montefiori, David C.', 'Davis, David', 'Weissenhorn, Winfried', 'McKnight, Áine', 'Heeney, Jonathan L.', 'Sallusto, Federica', 'Sattentau, Quentin J.', 'Weiss, Robin A.', 'Lanzavecchia, Antonio']",PLoS One,,,True
7bfb92f7dd06c758acfeecdccf82ccc541e7a250,PMC,Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals,http://dx.doi.org/10.1371/journal.pone.0008805,PMC2808385,20098712,CC BY,"BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.",2010 Jan 20,"['Corti, Davide', 'Langedijk, Johannes P. M.', 'Hinz, Andreas', 'Seaman, Michael S.', 'Vanzetta, Fabrizia', 'Fernandez-Rodriguez, Blanca M.', 'Silacci, Chiara', 'Pinna, Debora', 'Jarrossay, David', 'Balla-Jhagjhoorsingh, Sunita', 'Willems, Betty', 'Zekveld, Maria J.', 'Dreja, Hanna', ""O'Sullivan, Eithne"", 'Pade, Corinna', 'Orkin, Chloe', 'Jeffs, Simon A.', 'Montefiori, David C.', 'Davis, David', 'Weissenhorn, Winfried', 'McKnight, Áine', 'Heeney, Jonathan L.', 'Sallusto, Federica', 'Sattentau, Quentin J.', 'Weiss, Robin A.', 'Lanzavecchia, Antonio']",PLoS One,,,False
96b7cea86d9ad33fc927ddd3662c4283d0bb1aa7,PMC,Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals,http://dx.doi.org/10.1371/journal.pone.0008805,PMC2808385,20098712,CC BY,"BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.",2010 Jan 20,"['Corti, Davide', 'Langedijk, Johannes P. M.', 'Hinz, Andreas', 'Seaman, Michael S.', 'Vanzetta, Fabrizia', 'Fernandez-Rodriguez, Blanca M.', 'Silacci, Chiara', 'Pinna, Debora', 'Jarrossay, David', 'Balla-Jhagjhoorsingh, Sunita', 'Willems, Betty', 'Zekveld, Maria J.', 'Dreja, Hanna', ""O'Sullivan, Eithne"", 'Pade, Corinna', 'Orkin, Chloe', 'Jeffs, Simon A.', 'Montefiori, David C.', 'Davis, David', 'Weissenhorn, Winfried', 'McKnight, Áine', 'Heeney, Jonathan L.', 'Sallusto, Federica', 'Sattentau, Quentin J.', 'Weiss, Robin A.', 'Lanzavecchia, Antonio']",PLoS One,,,False
c5c5caecb4512142fc02aaad1c784183ae424d42,PMC,Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals,http://dx.doi.org/10.1371/journal.pone.0008805,PMC2808385,20098712,CC BY,"BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.",2010 Jan 20,"['Corti, Davide', 'Langedijk, Johannes P. M.', 'Hinz, Andreas', 'Seaman, Michael S.', 'Vanzetta, Fabrizia', 'Fernandez-Rodriguez, Blanca M.', 'Silacci, Chiara', 'Pinna, Debora', 'Jarrossay, David', 'Balla-Jhagjhoorsingh, Sunita', 'Willems, Betty', 'Zekveld, Maria J.', 'Dreja, Hanna', ""O'Sullivan, Eithne"", 'Pade, Corinna', 'Orkin, Chloe', 'Jeffs, Simon A.', 'Montefiori, David C.', 'Davis, David', 'Weissenhorn, Winfried', 'McKnight, Áine', 'Heeney, Jonathan L.', 'Sallusto, Federica', 'Sattentau, Quentin J.', 'Weiss, Robin A.', 'Lanzavecchia, Antonio']",PLoS One,,,False
012bbad97aa874f5f32645d80cee5526db164dd1,PMC,Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals,http://dx.doi.org/10.1371/journal.pone.0008805,PMC2808385,20098712,CC BY,"BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.",2010 Jan 20,"['Corti, Davide', 'Langedijk, Johannes P. M.', 'Hinz, Andreas', 'Seaman, Michael S.', 'Vanzetta, Fabrizia', 'Fernandez-Rodriguez, Blanca M.', 'Silacci, Chiara', 'Pinna, Debora', 'Jarrossay, David', 'Balla-Jhagjhoorsingh, Sunita', 'Willems, Betty', 'Zekveld, Maria J.', 'Dreja, Hanna', ""O'Sullivan, Eithne"", 'Pade, Corinna', 'Orkin, Chloe', 'Jeffs, Simon A.', 'Montefiori, David C.', 'Davis, David', 'Weissenhorn, Winfried', 'McKnight, Áine', 'Heeney, Jonathan L.', 'Sallusto, Federica', 'Sattentau, Quentin J.', 'Weiss, Robin A.', 'Lanzavecchia, Antonio']",PLoS One,,,False
dccd778c1e8d73adf7919681c1b0ff95395646f8,PMC,Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals,http://dx.doi.org/10.1371/journal.pone.0008805,PMC2808385,20098712,CC BY,"BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.",2010 Jan 20,"['Corti, Davide', 'Langedijk, Johannes P. M.', 'Hinz, Andreas', 'Seaman, Michael S.', 'Vanzetta, Fabrizia', 'Fernandez-Rodriguez, Blanca M.', 'Silacci, Chiara', 'Pinna, Debora', 'Jarrossay, David', 'Balla-Jhagjhoorsingh, Sunita', 'Willems, Betty', 'Zekveld, Maria J.', 'Dreja, Hanna', ""O'Sullivan, Eithne"", 'Pade, Corinna', 'Orkin, Chloe', 'Jeffs, Simon A.', 'Montefiori, David C.', 'Davis, David', 'Weissenhorn, Winfried', 'McKnight, Áine', 'Heeney, Jonathan L.', 'Sallusto, Federica', 'Sattentau, Quentin J.', 'Weiss, Robin A.', 'Lanzavecchia, Antonio']",PLoS One,,,False
19127add559e55feb42f8f2f97cda34f2d1e631e,PMC,Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals,http://dx.doi.org/10.1371/journal.pone.0008805,PMC2808385,20098712,CC BY,"BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.",2010 Jan 20,"['Corti, Davide', 'Langedijk, Johannes P. M.', 'Hinz, Andreas', 'Seaman, Michael S.', 'Vanzetta, Fabrizia', 'Fernandez-Rodriguez, Blanca M.', 'Silacci, Chiara', 'Pinna, Debora', 'Jarrossay, David', 'Balla-Jhagjhoorsingh, Sunita', 'Willems, Betty', 'Zekveld, Maria J.', 'Dreja, Hanna', ""O'Sullivan, Eithne"", 'Pade, Corinna', 'Orkin, Chloe', 'Jeffs, Simon A.', 'Montefiori, David C.', 'Davis, David', 'Weissenhorn, Winfried', 'McKnight, Áine', 'Heeney, Jonathan L.', 'Sallusto, Federica', 'Sattentau, Quentin J.', 'Weiss, Robin A.', 'Lanzavecchia, Antonio']",PLoS One,,,False
95d6b47d51b17a1f41ab4df0ed64086ebc11e589,PMC,Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza,http://dx.doi.org/10.1186/cc8208,PMC2811892,20003352,CC BY,"INTRODUCTION: Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. METHODS: We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. RESULTS: Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1β), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-γ) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-α, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. CONCLUSIONS: While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness.",2009 Dec 11,"['Bermejo-Martin, Jesus F', 'Ortiz de Lejarazu, Raul', 'Pumarola, Tomas', 'Rello, Jordi', 'Almansa, Raquel', 'Ramírez, Paula', 'Martin-Loeches, Ignacio', 'Varillas, David', 'Gallegos, Maria C', 'Serón, Carlos', 'Micheloud, Dariela', 'Gomez, Jose Manuel', 'Tenorio-Abreu, Alberto', 'Ramos, María J', 'Molina, M Lourdes', 'Huidobro, Samantha', 'Sanchez, Elia', 'Gordón, Mónica', 'Fernández, Victoria', 'del Castillo, Alberto', 'Marcos, Ma Ángeles', 'Villanueva, Beatriz', 'López, Carlos Javier', 'Rodríguez-Domínguez, Mario', 'Galan, Juan-Carlos', 'Cantón, Rafael', 'Lietor, Aurora', 'Rojo, Silvia', 'Eiros, Jose M', 'Hinojosa, Carmen', 'Gonzalez, Isabel', 'Torner, Nuria', 'Banner, David', 'Leon, Alberto', 'Cuesta, Pablo', 'Rowe, Thomas', 'Kelvin, David J']",Crit Care,,,True
02783b0989ab6a54fd4af139d787b69b9d9d009e,PMC,"Single Assay for Simultaneous Detection and Differential Identification of Human and Avian Influenza Virus Types, Subtypes, and Emergent Variants",http://dx.doi.org/10.1371/journal.pone.0008995,PMC2815781,20140251,CC0,"For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based) or remarkably insensitive (antibody-based). Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR) have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu) is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A/HN subtype, virulence, host-range, and resistance to antiviral agents.",2010 Feb 3,"['Metzgar, David', 'Myers, Christopher A.', 'Russell, Kevin L.', 'Faix, Dennis', 'Blair, Patrick J.', 'Brown, Jason', 'Vo, Scott', 'Swayne, David E.', 'Thomas, Colleen', 'Stenger, David A.', 'Lin, Baochuan', 'Malanoski, Anthony P.', 'Wang, Zheng', 'Blaney, Kate M.', 'Long, Nina C.', 'Schnur, Joel M.', 'Saad, Magdi D.', 'Borsuk, Lisa A.', 'Lichanska, Agnieszka M.', 'Lorence, Matthew C.', 'Weslowski, Brian', 'Schafer, Klaus O.', 'Tibbetts, Clark']",PLoS One,,,True
284790100b67133f3228466016a8f98ad096e24d,PMC,Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates,http://dx.doi.org/10.1371/journal.ppat.1000756,PMC2816697,20140198,CC BY,"The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.",2010 Feb 5,"['Smits, Saskia L.', 'de Lang, Anna', 'van den Brand, Judith M. A.', 'Leijten, Lonneke M.', 'van IJcken, Wilfred F.', 'Eijkemans, Marinus J. C.', 'van Amerongen, Geert', 'Kuiken, Thijs', 'Andeweg, Arno C.', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.']",PLoS Pathog,,,True
e2dd36baf975d279561e30fc21893f93dc006c24,PMC,Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates,http://dx.doi.org/10.1371/journal.ppat.1000756,PMC2816697,20140198,CC BY,"The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.",2010 Feb 5,"['Smits, Saskia L.', 'de Lang, Anna', 'van den Brand, Judith M. A.', 'Leijten, Lonneke M.', 'van IJcken, Wilfred F.', 'Eijkemans, Marinus J. C.', 'van Amerongen, Geert', 'Kuiken, Thijs', 'Andeweg, Arno C.', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.']",PLoS Pathog,,,False
89cef46c775f7e515544ba4e7c937a9793dabbc9,PMC,Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates,http://dx.doi.org/10.1371/journal.ppat.1000756,PMC2816697,20140198,CC BY,"The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.",2010 Feb 5,"['Smits, Saskia L.', 'de Lang, Anna', 'van den Brand, Judith M. A.', 'Leijten, Lonneke M.', 'van IJcken, Wilfred F.', 'Eijkemans, Marinus J. C.', 'van Amerongen, Geert', 'Kuiken, Thijs', 'Andeweg, Arno C.', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.']",PLoS Pathog,,,False
706e03d60c9ad429bc4c10195e0bc4adf189a409,PMC,Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates,http://dx.doi.org/10.1371/journal.ppat.1000756,PMC2816697,20140198,CC BY,"The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.",2010 Feb 5,"['Smits, Saskia L.', 'de Lang, Anna', 'van den Brand, Judith M. A.', 'Leijten, Lonneke M.', 'van IJcken, Wilfred F.', 'Eijkemans, Marinus J. C.', 'van Amerongen, Geert', 'Kuiken, Thijs', 'Andeweg, Arno C.', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.']",PLoS Pathog,,,False
cd9172cf6716c4ea412f4faefa5209cef6d403fb,PMC,Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates,http://dx.doi.org/10.1371/journal.ppat.1000756,PMC2816697,20140198,CC BY,"The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.",2010 Feb 5,"['Smits, Saskia L.', 'de Lang, Anna', 'van den Brand, Judith M. A.', 'Leijten, Lonneke M.', 'van IJcken, Wilfred F.', 'Eijkemans, Marinus J. C.', 'van Amerongen, Geert', 'Kuiken, Thijs', 'Andeweg, Arno C.', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.']",PLoS Pathog,,,False
808ff5aadc2181b9993ff7c050b4db8bd7f9625c,PMC,Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates,http://dx.doi.org/10.1371/journal.ppat.1000756,PMC2816697,20140198,CC BY,"The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.",2010 Feb 5,"['Smits, Saskia L.', 'de Lang, Anna', 'van den Brand, Judith M. A.', 'Leijten, Lonneke M.', 'van IJcken, Wilfred F.', 'Eijkemans, Marinus J. C.', 'van Amerongen, Geert', 'Kuiken, Thijs', 'Andeweg, Arno C.', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.']",PLoS Pathog,,,False
513d5ea4db4eb8e94c14c46b018c6041d78119cf,PMC,IPS-1 Is Essential for the Control of West Nile Virus Infection and Immunity,http://dx.doi.org/10.1371/journal.ppat.1000757,PMC2816698,20140199,CC BY,"The innate immune response is essential for controlling West Nile virus (WNV) infection but how this response is propagated and regulates adaptive immunity in vivo are not defined. Herein, we show that IPS-1, the central adaptor protein to RIG-I-like receptor (RLR) signaling, is essential for triggering of innate immunity and for effective development and regulation of adaptive immunity against pathogenic WNV. IPS-1(−/−) mice exhibited increased susceptibility to WNV infection marked by enhanced viral replication and dissemination with early viral entry into the CNS. Infection of cultured bone-marrow (BM) derived dendritic cells (DCs), macrophages (Macs), and primary cortical neurons showed that the IPS-1-dependent RLR signaling was essential for triggering IFN defenses and controlling virus replication in these key target cells of infection. Intriguingly, infected IPS-1(−/−) mice displayed uncontrolled inflammation that included elevated systemic type I IFN, proinflammatory cytokine and chemokine responses, increased numbers of inflammatory DCs, enhanced humoral responses marked by complete loss of virus neutralization activity, and increased numbers of virus-specific CD8+ T cells and non-specific immune cell proliferation in the periphery and in the CNS. This uncontrolled inflammatory response was associated with a lack of regulatory T cell expansion that normally occurs during acute WNV infection. Thus, the enhanced inflammatory response in the absence of IPS-1 was coupled with a failure to protect against WNV infection. Our data define an innate/adaptive immune interface mediated through IPS-1-dependent RLR signaling that regulates the quantity, quality, and balance of the immune response to WNV infection.",2010 Feb 5,"['Suthar, Mehul S.', 'Ma, Daphne Y.', 'Thomas, Sunil', 'Lund, Jennifer M.', 'Zhang, Nu', 'Daffis, Stephane', 'Rudensky, Alexander Y.', 'Bevan, Michael J.', 'Clark, Edward A.', 'Kaja, Murali-Krishna', 'Diamond, Michael S.', 'Gale, Michael']",PLoS Pathog,,,True
10abe76a05511196ea1f252383f0c70d592e7444,PMC,New Class of Monoclonal Antibodies against Severe Influenza: Prophylactic and Therapeutic Efficacy in Ferrets,http://dx.doi.org/10.1371/journal.pone.0009106,PMC2817000,20161706,CC BY,"BACKGROUND: The urgent medical need for innovative approaches to control influenza is emphasized by the widespread resistance of circulating subtype H1N1 viruses to the leading antiviral drug oseltamivir, the pandemic threat posed by the occurrences of human infections with highly pathogenic avian H5N1 viruses, and indeed the evolving swine-origin H1N1 influenza pandemic. A recently discovered class of human monoclonal antibodies with the ability to neutralize a broad spectrum of influenza viruses (including H1, H2, H5, H6 and H9 subtypes) has the potential to prevent and treat influenza in humans. Here we report the latest efficacy data for a representative antibody of this novel class. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. Survival rates, clinically relevant disease signs such as changes in body weight and temperature, virus replication in lungs and upper respiratory tract, as well as macro- and microscopic pathology were investigated. Prophylactic administration of 30 and 10 mg/kg CR6261 prior to viral challenge completely prevented mortality, weight loss and reduced the amount of infectious virus in the lungs by more than 99.9%, abolished shedding of virus in pharyngeal secretions and largely prevented H5N1-induced lung pathology. When administered therapeutically 1 day after challenge, 30 mg/kg CR6261 prevented death in all animals and blunted disease, as evidenced by decreased weight loss and temperature rise, reduced lung viral loads and shedding, and less lung damage. CONCLUSIONS/SIGNIFICANCE: These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza.",2010 Feb 8,"['Friesen, Robert H. E.', 'Koudstaal, Wouter', 'Koldijk, Martin H.', 'Weverling, Gerrit Jan', 'Brakenhoff, Just P. J.', 'Lenting, Peter J.', 'Stittelaar, Koert J.', 'Osterhaus, Albert D. M. E.', 'Kompier, Ronald', 'Goudsmit, Jaap']",PLoS One,,,True
0768babd4f340cc1b5eb49540be3decfc480eb8b,PMC,Synonymous Codon Usage Analysis of Thirty Two Mycobacteriophage Genomes,http://dx.doi.org/10.1155/2009/316936,PMC2817497,20150956,CC BY,"Synonymous codon usage of protein coding genes of thirty two completely sequenced mycobacteriophage genomes was studied using multivariate statistical analysis. One of the major factors influencing codon usage is identified to be compositional bias. Codons ending with either C or G are preferred in highly expressed genes among which C ending codons are highly preferred over G ending codons. A strong negative correlation between effective number of codons (Nc) and GC3s content was also observed, showing that the codon usage was effected by gene nucleotide composition. Translational selection is also identified to play a role in shaping the codon usage operative at the level of translational accuracy. High level of heterogeneity is seen among and between the genomes. Length of genes is also identified to influence the codon usage in 11 out of 32 phage genomes. Mycobacteriophage Cooper is identified to be the highly biased genome with better translation efficiency comparing well with the host specific tRNA genes.",2009 Feb 1,"['Hassan, Sameer', 'Mahalingam, Vasantha', 'Kumar, Vanaja']",Adv Bioinformatics,,,True
cafc9ffe47534a504ae1036e5b7299d80f49beb5,PMC,Paleovirology—Modern Consequences of Ancient Viruses,http://dx.doi.org/10.1371/journal.pbio.1000301,PMC2817711,20161719,CC BY,,2010 Feb 9,"['Emerman, Michael', 'Malik, Harmit S.']",PLoS Biol,,,True
b0a17b1f4447f0a81d2e93f2e23720feadee96cd,PMC,Mathematical Modeling of the Effectiveness of Facemasks in Reducing the Spread of Novel Influenza A (H1N1),http://dx.doi.org/10.1371/journal.pone.0009018,PMC2818714,20161764,CC BY,"On June 11, 2009, the World Health Organization declared the outbreak of novel influenza A (H1N1) a pandemic. With limited supplies of antivirals and vaccines, countries and individuals are looking at other ways to reduce the spread of pandemic (H1N1) 2009, particularly options that are cost effective and relatively easy to implement. Recent experiences with the 2003 SARS and 2009 H1N1 epidemics have shown that people are willing to wear facemasks to protect themselves against infection; however, little research has been done to quantify the impact of using facemasks in reducing the spread of disease. We construct and analyze a mathematical model for a population in which some people wear facemasks during the pandemic and quantify impact of these masks on the spread of influenza. To estimate the parameter values used for the effectiveness of facemasks, we used available data from studies on N95 respirators and surgical facemasks. The results show that if N95 respirators are only 20% effective in reducing susceptibility and infectivity, only 10% of the population would have to wear them to reduce the number of influenza A (H1N1) cases by 20%. We can conclude from our model that, if worn properly, facemasks are an effective intervention strategy in reducing the spread of pandemic (H1N1) 2009.",2010 Feb 10,"['Tracht, Samantha M.', 'Del Valle, Sara Y.', 'Hyman, James M.']",PLoS One,,,True
aa8a9f4a432fa52294b1fa674b3ffbeadeff563f,PMC,Human Coronavirus NL63 Open Reading Frame 3 encodes a virion-incorporated N-glycosylated membrane protein,http://dx.doi.org/10.1186/1743-422X-7-6,PMC2819038,20078868,CC BY,"BACKGROUND: Human pathogenic coronavirus NL63 (hCoV-NL63) is a group 1 (alpha) coronavirus commonly associated with respiratory tract infections. In addition to known non-structural and structural proteins all coronaviruses have one or more accessory proteins whose functions are mostly unknown. Our study focuses on hCoV-NL63 open reading frame 3 (ORF 3) which is a highly conserved accessory protein among coronaviruses. RESULTS: In-silico analysis of the 225 amino acid sequence of hCoV-NL63 ORF 3 predicted a triple membrane-spanning protein. Expression in infected CaCo-2 and LLC-MK2 cells was confirmed by immunofluorescence and Western blot analysis. The protein was detected within the endoplasmatic reticulum/Golgi intermediate compartment (ERGIC) where coronavirus assembly and budding takes place. Subcellular localization studies using recombinant ORF 3 protein transfected in Huh-7 cells revealed occurrence in ERGIC, Golgi- and lysosomal compartments. By fluorescence microscopy of differently tagged envelope (E), membrane (M) and nucleocapsid (N) proteins it was shown that ORF 3 protein colocalizes extensively with E and M within the ERGIC. Using N-terminally FLAG-tagged ORF 3 protein and an antiserum specific to the C-terminus we verified the proposed topology of an extracellular N-terminus and a cytosolic C-terminus. By in-vitro translation analysis and subsequent endoglycosidase H digestion we showed that ORF 3 protein is N-glycosylated at the N-terminus. Analysis of purified viral particles revealed that ORF 3 protein is incorporated into virions and is therefore an additional structural protein. CONCLUSIONS: This study is the first extensive expression analysis of a group 1 hCoV-ORF 3 protein. We give evidence that ORF 3 protein is a structural N-glycosylated and virion-incorporated protein.",2010 Jan 15,"['Müller, Marcel A', 'van der Hoek, Lia', 'Voss, Daniel', 'Bader, Oliver', 'Lehmann, Dörte', 'Schulz, Axel R', 'Kallies, Stephan', 'Suliman, Tasnim', 'Fielding, Burtram C', 'Drosten, Christian', 'Niedrig, Matthias']",Virol J,,,True
fe1dea09375e7ab4f239b5c57cd522fc05ff3e37,PMC,"Avian Colibacillosis and Salmonellosis: A Closer Look at Epidemiology, Pathogenesis, Diagnosis, Control and Public Health Concerns",http://dx.doi.org/10.3390/ijerph7010089,PMC2819778,20195435,CC BY,"Avian colibacillosis and salmonellosis are considered to be the major bacterial diseases in the poultry industry world-wide. Colibacillosis and salmonellosis are the most common avian diseases that are communicable to humans. This article provides the vital information on the epidemiology, pathogenesis, diagnosis, control and public health concerns of avian colibacillosis and salmonellosis. A better understanding of the information addressed in this review article will assist the poultry researchers and the poultry industry in continuing to make progress in reducing and eliminating avian colibacillosis and salmonellosis from the poultry flocks, thereby reducing potential hazards to the public health posed by these bacterial diseases.",2010 Jan 12,"Lutful Kabir, S. M.",Int J Environ Res Public Health,,,True
e4d6c7b63c33ac798572f0e53ab6b53a2f71b452,PMC,Correcting the Actual Reproduction Number: A Simple Method to Estimate R(0) from Early Epidemic Growth Data,http://dx.doi.org/10.3390/ijerph7010291,PMC2819789,20195446,CC BY,"The basic reproduction number, R(0), a summary measure of the transmission potential of an infectious disease, is estimated from early epidemic growth rate, but a likelihood-based method for the estimation has yet to be developed. The present study corrects the concept of the actual reproduction number, offering a simple framework for estimating R(0) without assuming exponential growth of cases. The proposed method is applied to the HIV epidemic in European countries, yielding R(0) values ranging from 3.60 to 3.74, consistent with those based on the Euler-Lotka equation. The method also permits calculating the expected value of R(0) using a spreadsheet.",2010 Jan 21,"Nishiura, Hiroshi",Int J Environ Res Public Health,,,True
c41cd165529d51d5418e2628ceda43970f8ca399,PMC,Evidence that Gag facilitates HIV-1 envelope association both in GPI-enriched plasma membrane and detergent resistant membranes and facilitates envelope incorporation onto virions in primary CD4(+ )T cells,http://dx.doi.org/10.1186/1743-422X-7-3,PMC2820015,20064199,CC BY,"HIV-1 particle assembly mediated by viral Gag protein occurs predominantly at plasma membrane. While colocalization of HIV-1 envelope with lipid rich microenvironment have been shown in T cells, the significance of viral proteins modulating envelope association in such microdomains in plasma membrane enriched in glycosylphosphatidylinositol-anchored proteins in primary CD4(+ )T cells that are natural targets of HIV-1 is poorly understood. Here we show that in primary CD4(+ )T cells that are natural targets of HIV-1 in vivo, Gag modulates HIV-1 envelope association with GM1 ganglioside and CD59 rich cellular compartments as well as with detergent resistant membranes. Our data strengthen evidence that Gag-Env interaction is important in envelope association with lipid rafts containing GPI-anchored proteins for efficient assembly onto mature virions resulting in productive infection of primary CD4(+ )T cells.",2010 Jan 8,"['Patil, Ajit', 'Gautam, Archana', 'Bhattacharya, Jayanta']",Virol J,,,True
1cf0ff471514dc73eaa490d65d0d4a35f1345f6e,PMC,"Novel Virus Influenza A (H1N1sw) in South-Eastern France, April-August 2009",http://dx.doi.org/10.1371/journal.pone.0009214,PMC2822845,20174643,CC BY,"BACKGROUND: In April 2009, the first cases of pandemic (H1N1)-2009 influenza [H1N1sw] virus were detected in France. Virological surveillance was undertaken in reference laboratories of the seven French Defence Zones. METHODOLOGY/PRINCIPAL FINDINGS: We report results of virological analyses performed in the Public Hospitals of Marseille during the first months of the outbreak. (i) Nasal swabs were tested using rapid influenza diagnostic test (RIDT) and two RT-PCR assays. Epidemiological characteristics of the 99 first suspected cases were analyzed, including detection of influenza virus and 18 other respiratory viruses. During three months, a total of 1,815 patients were tested (including 236 patients infected H1N1sw virus) and distribution in age groups and results of RIDT were analyzed. (ii) 600 sera received before April 2009 and randomly selected from in-patients were tested by a standard hemagglutination inhibition assay for antibody to the novel H1N1sw virus. (iii) One early (May 2009) and one late (July 2009) viral isolates were characterized by sequencing the complete hemagglutinine and neuraminidase genes. (iiii) Epidemiological characteristics of a cluster of cases that occurred in July 2009 in a summer camp were analyzed. CONCLUSIONS/SIGNIFICANCE: This study presents new virological and epidemiological data regarding infection by the pandemic A/H1N1 virus in Europe. Distribution in age groups was found to be similar to that previously reported for seasonal H1N1. The first seroprevalence data made available for a European population suggest a previous exposure of individuals over 40 years old to influenza viruses antigenically related to the pandemic (H1N1)-2009 virus. Genomic analysis indicates that strains harbouring a new amino-acid pattern in the neuraminidase gene appeared secondarily and tended to supplant the first strains. Finally, in contrast with previous reports, our data support the use of RIDT for the detection of infection in children, especially in the context of the investigation of grouped cases.",2010 Feb 17,"['Nougairède, Antoine', 'Ninove, Laetitia', 'Zandotti, Christine', 'Salez, Nicolas', 'Mantey, Karine', 'Resseguier, Noémie', 'Gazin, Céline', 'Raoult, Didier', 'Charrel, Rémi N.', 'de Lamballerie, Xavier']",PLoS One,,,True
e5db7954926b0072fa6bf086899e4faf42c15f3a,PMC,An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses,http://dx.doi.org/10.1186/1743-422X-7-9,PMC2823673,20082709,CC BY,"BACKGROUND: A growing concern has raised regarding the pandemic potential of the highly pathogenic avian influenza (HPAI) H5N1 viruses. Consequently, there is an urgent need to develop an effective and safe vaccine against the divergent H5N1 influenza viruses. In the present study, we designed a tetra-branched multiple antigenic peptide (MAP)-based vaccine, designated M2e-MAP, which contains the sequence overlapping the highly conserved extracellular domain of matrix protein 2 (M2e) of a HPAI H5N1 virus, and investigated its immune responses and cross-protection against different clades of H5N1 viruses. RESULTS: Our results showed that M2e-MAP vaccine induced strong M2e-specific IgG antibody responses following 3-dose immunization of mice with M2e-MAP in the presence of Freunds' or aluminium (alum) adjuvant. M2e-MAP vaccination limited viral replication and attenuated histopathological damage in the challenged mouse lungs. The M2e-MAP-based vaccine protected immunized mice against both clade1: VN/1194 and clade2.3.4: SZ/406H H5N1 virus challenge, being able to counteract weight lost and elevate survival rate following lethal challenge of H5N1 viruses. CONCLUSIONS: These results suggest that M2e-MAP presenting M2e of H5N1 virus has a great potential to be developed into an effective subunit vaccine for the prevention of infection by a broad spectrum of HPAI H5N1 viruses.",2010 Jan 18,"['Zhao, Guangyu', 'Lin, Yongping', 'Du, Lanying', 'Guan, Jie', 'Sun, Shihui', 'Sui, Hongyan', 'Kou, Zhihua', 'Chan, Chris CS', 'Guo, Yan', 'Jiang, Shibo', 'Zheng, Bo-Jian', 'Zhou, Yusen']",Virol J,,,True
3568da162b8d9f5356c9264193b6292efa3d9556,PMC,Arterivirus Nsp1 Modulates the Accumulation of Minus-Strand Templates to Control the Relative Abundance of Viral mRNAs,http://dx.doi.org/10.1371/journal.ppat.1000772,PMC2824749,20174607,CC BY,"The gene expression of plus-strand RNA viruses with a polycistronic genome depends on translation and replication of the genomic mRNA, as well as synthesis of subgenomic (sg) mRNAs. Arteriviruses and coronaviruses, distantly related members of the nidovirus order, employ a unique mechanism of discontinuous minus-strand RNA synthesis to generate subgenome-length templates for the synthesis of a nested set of sg mRNAs. Non-structural protein 1 (nsp1) of the arterivirus equine arteritis virus (EAV), a multifunctional regulator of viral RNA synthesis and virion biogenesis, was previously implicated in controlling the balance between genome replication and sg mRNA synthesis. Here, we employed reverse and forward genetics to gain insight into the multiple regulatory roles of nsp1. Our analysis revealed that the relative abundance of viral mRNAs is tightly controlled by an intricate network of interactions involving all nsp1 subdomains. Distinct nsp1 mutations affected the quantitative balance among viral mRNA species, and our data implicate nsp1 in controlling the accumulation of full-length and subgenome-length minus-strand templates for viral mRNA synthesis. The moderate differential changes in viral mRNA abundance of nsp1 mutants resulted in similarly altered viral protein levels, but progeny virus yields were greatly reduced. Pseudorevertant analysis provided compelling genetic evidence that balanced EAV mRNA accumulation is critical for efficient virus production. This first report on protein-mediated, mRNA-specific control of nidovirus RNA synthesis reveals the existence of an integral control mechanism to fine-tune replication, sg mRNA synthesis, and virus production, and establishes a major role for nsp1 in coordinating the arterivirus replicative cycle.",2010 Feb 19,"['Nedialkova, Danny D.', 'Gorbalenya, Alexander E.', 'Snijder, Eric J.']",PLoS Pathog,,,True
d9e06d074df536664275030a32f54ff8d8bb0361,PMC,The Disulfide Bonds in Glycoprotein E2 of Hepatitis C Virus Reveal the Tertiary Organization of the Molecule,http://dx.doi.org/10.1371/journal.ppat.1000762,PMC2824758,20174556,CC BY,"Hepatitis C virus (HCV), a major cause of chronic liver disease in humans, is the focus of intense research efforts worldwide. Yet structural data on the viral envelope glycoproteins E1 and E2 are scarce, in spite of their essential role in the viral life cycle. To obtain more information, we developed an efficient production system of recombinant E2 ectodomain (E2e), truncated immediately upstream its trans-membrane (TM) region, using Drosophila melanogaster cells. This system yields a majority of monomeric protein, which can be readily separated chromatographically from contaminating disulfide-linked aggregates. The isolated monomeric E2e reacts with a number of conformation-sensitive monoclonal antibodies, binds the soluble CD81 large external loop and efficiently inhibits infection of Huh7.5 cells by infectious HCV particles (HCVcc) in a dose-dependent manner, suggesting that it adopts a native conformation. These properties of E2e led us to experimentally determine the connectivity of its 9 disulfide bonds, which are strictly conserved across HCV genotypes. Furthermore, circular dichroism combined with infrared spectroscopy analyses revealed the secondary structure contents of E2e, indicating in particular about 28% β-sheet, in agreement with the consensus secondary structure predictions. The disulfide connectivity pattern, together with data on the CD81 binding site and reported E2 deletion mutants, enabled the threading of the E2e polypeptide chain onto the structural template of class II fusion proteins of related flavi- and alphaviruses. The resulting model of the tertiary organization of E2 gives key information on the antigenicity determinants of the virus, maps the receptor binding site to the interface of domains I and III, and provides insight into the nature of a putative fusogenic conformational change.",2010 Feb 19,"['Krey, Thomas', ""d'Alayer, Jacques"", 'Kikuti, Carlos M.', 'Saulnier, Aure', 'Damier-Piolle, Laurence', 'Petitpas, Isabelle', 'Johansson, Daniel X.', 'Tawar, Rajiv G.', 'Baron, Bruno', 'Robert, Bruno', 'England, Patrick', 'Persson, Mats A. A.', 'Martin, Annette', 'Rey, Félix A.']",PLoS Pathog,,,True
d819ba39c114acf69059a2d37f21246f30edaf56,PMC,The Disulfide Bonds in Glycoprotein E2 of Hepatitis C Virus Reveal the Tertiary Organization of the Molecule,http://dx.doi.org/10.1371/journal.ppat.1000762,PMC2824758,20174556,CC BY,"Hepatitis C virus (HCV), a major cause of chronic liver disease in humans, is the focus of intense research efforts worldwide. Yet structural data on the viral envelope glycoproteins E1 and E2 are scarce, in spite of their essential role in the viral life cycle. To obtain more information, we developed an efficient production system of recombinant E2 ectodomain (E2e), truncated immediately upstream its trans-membrane (TM) region, using Drosophila melanogaster cells. This system yields a majority of monomeric protein, which can be readily separated chromatographically from contaminating disulfide-linked aggregates. The isolated monomeric E2e reacts with a number of conformation-sensitive monoclonal antibodies, binds the soluble CD81 large external loop and efficiently inhibits infection of Huh7.5 cells by infectious HCV particles (HCVcc) in a dose-dependent manner, suggesting that it adopts a native conformation. These properties of E2e led us to experimentally determine the connectivity of its 9 disulfide bonds, which are strictly conserved across HCV genotypes. Furthermore, circular dichroism combined with infrared spectroscopy analyses revealed the secondary structure contents of E2e, indicating in particular about 28% β-sheet, in agreement with the consensus secondary structure predictions. The disulfide connectivity pattern, together with data on the CD81 binding site and reported E2 deletion mutants, enabled the threading of the E2e polypeptide chain onto the structural template of class II fusion proteins of related flavi- and alphaviruses. The resulting model of the tertiary organization of E2 gives key information on the antigenicity determinants of the virus, maps the receptor binding site to the interface of domains I and III, and provides insight into the nature of a putative fusogenic conformational change.",2010 Feb 19,"['Krey, Thomas', ""d'Alayer, Jacques"", 'Kikuti, Carlos M.', 'Saulnier, Aure', 'Damier-Piolle, Laurence', 'Petitpas, Isabelle', 'Johansson, Daniel X.', 'Tawar, Rajiv G.', 'Baron, Bruno', 'Robert, Bruno', 'England, Patrick', 'Persson, Mats A. A.', 'Martin, Annette', 'Rey, Félix A.']",PLoS Pathog,,,True
e9bcf05233a1b2f6b7a37e98d950ee976ae592e1,PMC,The Disulfide Bonds in Glycoprotein E2 of Hepatitis C Virus Reveal the Tertiary Organization of the Molecule,http://dx.doi.org/10.1371/journal.ppat.1000762,PMC2824758,20174556,CC BY,"Hepatitis C virus (HCV), a major cause of chronic liver disease in humans, is the focus of intense research efforts worldwide. Yet structural data on the viral envelope glycoproteins E1 and E2 are scarce, in spite of their essential role in the viral life cycle. To obtain more information, we developed an efficient production system of recombinant E2 ectodomain (E2e), truncated immediately upstream its trans-membrane (TM) region, using Drosophila melanogaster cells. This system yields a majority of monomeric protein, which can be readily separated chromatographically from contaminating disulfide-linked aggregates. The isolated monomeric E2e reacts with a number of conformation-sensitive monoclonal antibodies, binds the soluble CD81 large external loop and efficiently inhibits infection of Huh7.5 cells by infectious HCV particles (HCVcc) in a dose-dependent manner, suggesting that it adopts a native conformation. These properties of E2e led us to experimentally determine the connectivity of its 9 disulfide bonds, which are strictly conserved across HCV genotypes. Furthermore, circular dichroism combined with infrared spectroscopy analyses revealed the secondary structure contents of E2e, indicating in particular about 28% β-sheet, in agreement with the consensus secondary structure predictions. The disulfide connectivity pattern, together with data on the CD81 binding site and reported E2 deletion mutants, enabled the threading of the E2e polypeptide chain onto the structural template of class II fusion proteins of related flavi- and alphaviruses. The resulting model of the tertiary organization of E2 gives key information on the antigenicity determinants of the virus, maps the receptor binding site to the interface of domains I and III, and provides insight into the nature of a putative fusogenic conformational change.",2010 Feb 19,"['Krey, Thomas', ""d'Alayer, Jacques"", 'Kikuti, Carlos M.', 'Saulnier, Aure', 'Damier-Piolle, Laurence', 'Petitpas, Isabelle', 'Johansson, Daniel X.', 'Tawar, Rajiv G.', 'Baron, Bruno', 'Robert, Bruno', 'England, Patrick', 'Persson, Mats A. A.', 'Martin, Annette', 'Rey, Félix A.']",PLoS Pathog,,,False
b85794a3749932e7585c864b7fbb766f38dd97f6,PMC,Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach,http://dx.doi.org/10.1371/journal.pgen.1000849,PMC2824813,20174570,CC BY,"Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of different viruses in a geographic region) was used to measure virus-driven selective pressure. Results showed an excess of variants correlated with virus diversity in genes involved in immune response and in the biosynthesis of glycan structures functioning as viral receptors; a significantly higher than expected number of variants was also seen in genes encoding proteins that directly interact with viral components. Genome-wide analyses identified 441 variants significantly associated with virus-diversity; these are more frequently located within gene regions than expected, and they map to 139 human genes. Analysis of functional relationships among genes subjected to virus-driven selective pressure identified a complex network enriched in viral products-interacting proteins. The novel approach to the study of infectious disease epidemiology presented herein may represent an alternative to classic genome-wide association studies and provides a large set of candidate susceptibility variants for viral infections.",2010 Feb 19,"['Fumagalli, Matteo', 'Pozzoli, Uberto', 'Cagliani, Rachele', 'Comi, Giacomo P.', 'Bresolin, Nereo', 'Clerici, Mario', 'Sironi, Manuela']",PLoS Genet,,,True
0d543b40bcecd9573a4dbe14f2231f48554da3c1,PMC,Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach,http://dx.doi.org/10.1371/journal.pgen.1000849,PMC2824813,20174570,CC BY,"Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of different viruses in a geographic region) was used to measure virus-driven selective pressure. Results showed an excess of variants correlated with virus diversity in genes involved in immune response and in the biosynthesis of glycan structures functioning as viral receptors; a significantly higher than expected number of variants was also seen in genes encoding proteins that directly interact with viral components. Genome-wide analyses identified 441 variants significantly associated with virus-diversity; these are more frequently located within gene regions than expected, and they map to 139 human genes. Analysis of functional relationships among genes subjected to virus-driven selective pressure identified a complex network enriched in viral products-interacting proteins. The novel approach to the study of infectious disease epidemiology presented herein may represent an alternative to classic genome-wide association studies and provides a large set of candidate susceptibility variants for viral infections.",2010 Feb 19,"['Fumagalli, Matteo', 'Pozzoli, Uberto', 'Cagliani, Rachele', 'Comi, Giacomo P.', 'Bresolin, Nereo', 'Clerici, Mario', 'Sironi, Manuela']",PLoS Genet,,,False
c5519427a4559ac86ef69166403d0c2e9a90b690,PMC,Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach,http://dx.doi.org/10.1371/journal.pgen.1000849,PMC2824813,20174570,CC BY,"Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of different viruses in a geographic region) was used to measure virus-driven selective pressure. Results showed an excess of variants correlated with virus diversity in genes involved in immune response and in the biosynthesis of glycan structures functioning as viral receptors; a significantly higher than expected number of variants was also seen in genes encoding proteins that directly interact with viral components. Genome-wide analyses identified 441 variants significantly associated with virus-diversity; these are more frequently located within gene regions than expected, and they map to 139 human genes. Analysis of functional relationships among genes subjected to virus-driven selective pressure identified a complex network enriched in viral products-interacting proteins. The novel approach to the study of infectious disease epidemiology presented herein may represent an alternative to classic genome-wide association studies and provides a large set of candidate susceptibility variants for viral infections.",2010 Feb 19,"['Fumagalli, Matteo', 'Pozzoli, Uberto', 'Cagliani, Rachele', 'Comi, Giacomo P.', 'Bresolin, Nereo', 'Clerici, Mario', 'Sironi, Manuela']",PLoS Genet,,,False
ec3316b6d33659c1070099a4395a1c25eeacc446,PMC,"Triple Combination of Amantadine, Ribavirin, and Oseltamivir Is Highly Active and Synergistic against Drug Resistant Influenza Virus Strains In Vitro",http://dx.doi.org/10.1371/journal.pone.0009332,PMC2825274,20179772,CC0,"The rapid emergence and subsequent spread of the novel 2009 Influenza A/H1N1 virus (2009 H1N1) has prompted the World Health Organization to declare the first pandemic of the 21(st) century, highlighting the threat of influenza to public health and healthcare systems. Widespread resistance to both classes of influenza antivirals (adamantanes and neuraminidase inhibitors) occurs in both pandemic and seasonal viruses, rendering these drugs to be of marginal utility in the treatment modality. Worldwide, virtually all 2009 H1N1 and seasonal H3N2 strains are resistant to the adamantanes (rimantadine and amantadine), and the majority of seasonal H1N1 strains are resistant to oseltamivir, the most widely prescribed neuraminidase inhibitor (NAI). To address the need for more effective therapy, we evaluated the in vitro activity of a triple combination antiviral drug (TCAD) regimen composed of drugs with different mechanisms of action against drug-resistant seasonal and 2009 H1N1 influenza viruses. Amantadine, ribavirin, and oseltamivir, alone and in combination, were tested against amantadine- and oseltamivir-resistant influenza A viruses using an in vitro infection model in MDCK cells. Our data show that the triple combination was highly synergistic against drug-resistant viruses, and the synergy of the triple combination was significantly greater than the synergy of any double combination tested (P<0.05), including the combination of two NAIs. Surprisingly, amantadine and oseltamivir contributed to the antiviral activity of the TCAD regimen against amantadine- and oseltamivir-resistant viruses, respectively, at concentrations where they had no activity as single agents, and at concentrations that were clinically achievable. Our data demonstrate that the TCAD regimen composed of amantadine, ribavirin, and oseltamivir is highly synergistic against resistant viruses, including 2009 H1N1. The TCAD regimen overcomes baseline drug resistance to both classes of approved influenza antivirals, and thus may represent a highly active antiviral therapy for seasonal and pandemic influenza.",2010 Feb 22,"['Nguyen, Jack T.', 'Hoopes, Justin D.', 'Le, Minh H.', 'Smee, Donald F.', 'Patick, Amy K.', 'Faix, Dennis J.', 'Blair, Patrick J.', 'de Jong, Menno D.', 'Prichard, Mark N.', 'Went, Gregory T.']",PLoS One,,,True
165d5a3cf0dc10f8229b0c6fcf149cd244cbd73a,PMC,Evolution and emergence of novel human infections,http://dx.doi.org/10.1098/rspb.2009.1059,PMC2825776,19692402,CC BY,"Some zoonotic pathogens cause sporadic infection in humans but rarely propagate further, while others have succeeded in overcoming the species barrier and becoming established in the human population. Adaptation, driven by selection pressure in human hosts, can play a significant role in allowing pathogens to cross this species barrier. Here we use a simple mathematical model to study potential epidemiological markers of adaptation. We ask: under what circumstances could ongoing adaptation be signalled by large clusters of human infection? If a pathogen has caused hundreds of cases but with little transmission, does this indicate that the species barrier cannot be crossed? Finally, how can case reports be monitored to detect an imminent emergence event? We distinguish evolutionary scenarios under which adaptation is likely to be signalled by large clusters of infection and under which emergence is likely to occur without any prior warning. Moreover, we show that a lack of transmission never rules out adaptability, regardless of how many zoonoses have occurred. Indeed, after the first 100 zoonotic cases, continuing sporadic zoonotic infections without onward, human-to-human transmission offer little extra information on pathogen adaptability. Finally, we present a simple method for monitoring outbreaks for signs of emergence and discuss public health implications.",2009 Nov 22,"['Arinaminpathy, N.', 'McLean, A. R.']",Proc Biol Sci,,,True
f5dd178e6cfe607d118df9d16716cd68605dbee4,PMC,The Feasibility of Canine Rabies Elimination in Africa: Dispelling Doubts with Data,http://dx.doi.org/10.1371/journal.pntd.0000626,PMC2826407,20186330,CC BY,"BACKGROUND: Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent. METHODOLOGY/PRINCIPAL FINDINGS: This paper identifies four common reasons given for the lack of effective canine rabies control in Africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. We address each of these issues in turn, presenting data from field studies and modelling approaches used in Tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention. CONCLUSIONS/SIGNIFICANCE: We conclude that there are no insurmountable problems to canine rabies control in most of Africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths.",2010 Feb 23,"['Lembo, Tiziana', 'Hampson, Katie', 'Kaare, Magai T.', 'Ernest, Eblate', 'Knobel, Darryn', 'Kazwala, Rudovick R.', 'Haydon, Daniel T.', 'Cleaveland, Sarah']",PLoS Negl Trop Dis,,,True
3ebd3fb346c40a654f1f9d8e48ef8daa1902d406,PMC,Descriptive distribution and phylogenetic analysis of feline infectious peritonitis virus isolates of Malaysia,http://dx.doi.org/10.1186/1751-0147-52-1,PMC2828449,20053278,CC BY,"The descriptive distribution and phylogeny of feline coronaviruses (FCoVs) were studied in cats suspected of having feline infectious peritonitis (FIP) in Malaysia. Ascitic fluids and/or biopsy samples were subjected to a reverse transcription polymerase chain reaction (RT-PCR) targeted for a conserved region of 3'untranslated region (3'UTR) of the FCoV genome. Eighty nine percent of the sampled animals were positive for the presence of FCoV. Among the FCoV positive cats, 80% of cats were males and 64% were below 2 years of age. The FCoV positive cases included 56% domestic short hair (DSH), 40% Persian, and 4% Siamese cats. The nucleotide sequences of 10 selected amplified products from FIP cases were determined. The sequence comparison revealed that the field isolates had 96% homology with a few point mutations. The extent of homology decreased to 93% when compared with reference strains. The overall branching pattern of phylogenetic tree showed two distinct clusters, where all Malaysian isolates fall into one main genetic cluster. These findings provided the first genetic information of FCoV in Malaysia.",2010 Jan 6,"['Sharif, Saeed', 'Arshad, Siti S', 'Hair-Bejo, Mohd', 'Omar, Abdul R', 'Zeenathul, Nazariah A', 'Fong, Lau S', 'Rahman, Nor-Alimah', 'Arshad, Habibah', 'Shamsudin, Shahirudin', 'Isa, Mohd-Kamarudin A']",Acta Vet Scand,,,True
c92099607cfae94a24e03a111d12994535cc2eae,PMC,A new therapeutic strategy for lung tissue injury induced by influenza with CR2 targeting complement inhibitior,http://dx.doi.org/10.1186/1743-422X-7-30,PMC2829536,20144216,CC BY,"BACKGROUND: Influenza is a respiratory disease that seriously threatens human health. In fact, influenza virus itself does not make critical contribution to mortality induced by influenza, but ""cytokine storm"" produced by the excessive immune response triggered by the virus can result in inflammatory reaction of lung tissues and fatal lung tissue injury, and thus increase influenza mortality. Therefore, besides antiviral drugs, immunosuppression drugs should also be included in infection treatment. PRESENTATION OF THE HYPOTHESIS: Complement is the center of inflammatory reaction. If complement system is over activated, the body will have strong inflammatory reaction or tissue injury, resulting in pathological process. Many studies have proved that, inflammatory injury of lung tissues caused by influenza virus is closely related to complement activation. Therefore, inhibiting complement activation can significantly reduce inflammatory injury in lung tissues. As complement is both a physiological defense and pathological damage medium, systematic inhibition may result in side effects including infection. Therefore, we design targeting complement inhibitors for complement activation sites, i.e. with CR2 as targeting vector, complement inhibitors like CD59 and Crry are targeted to inflammatory sites to specially inhibit the complement activation in local injury, thus local inflammatory reaction is inhibited. TESTING THE HYPOTHESIS: CR2-CD59 and CR2-Crry targeting complement inhibitors are fusion-expressed, and their biological activity is examined via in vivo and in vitro tests. CR2 targeting complement inhibitors are used to treat mouse influenza viral pneumonia model, with PBS treatment group as the control. The survival and lung tissue injury of the mice is observed and the effect of CR2 targeting complement inhibitors on pneumonia induced by influenza virus is evaluated. IMPLICATIONS OF THE HYPOTHESIS: CR2 targeting complement inhibitors are expected to be ideal drugs for viral pneumonia.",2010 Feb 9,"['Zhang, Chuanfu', 'Xu, Yuanyong', 'Jia, Leili', 'Yang, Yutao', 'Wang, Yong', 'Sun, Yansong', 'Huang, Liuyu', 'Qiao, Fei', 'Tomlinson, Stephen', 'Liu, Xuelin', 'Zhou, Yusen', 'Song, Hongbin']",Virol J,,,True
b187316c24eb26f96af6ebbc243e90cfc504d94b,PMC,High-level expression and purification of soluble recombinant FGF21 protein by SUMO fusion in Escherichia coli,http://dx.doi.org/10.1186/1472-6750-10-14,PMC2831817,20163718,CC BY,"BACKGROUND: Fibroblast growth factor 21 (FGF21) is a promising drug candidate to combat metabolic diseases. However, high-level expression and purification of recombinant FGF21 (rFGF21) in Escherichia coli (E. coli) is difficult because rFGF21 forms inclusion bodies in the bacteria making it difficult to purify and obtain high concentrations of bioactive rFGF21. To overcome this problem, we fused the FGF21 with SUMO (Small ubiquitin-related modifier) by polymerase chain reaction (PCR), and expressed the fused gene in E. coli BL21(DE3). RESULTS: By inducing with IPTG, SUMO-FGF21 was expressed at a high level. Its concentration reached 30% of total protein, and exceeded 95% of all soluble proteins. The fused protein was purified by DEAE sepharose FF and Ni-NTA affinity chromatography. Once cleaved by the SUMO protease, the purity of rFGF21 by high performance liquid chromatography (HPLC) was shown to be higher than 96% with low endotoxin level (<1.0 EU/ml). The results of in vivo animal experiments showed that rFGF21 produced by using this method, could decrease the concentration of plasma glucose in diabetic rats by streptozotocin (STZ) injection. CONCLUSIONS: This study demonstrated that SUMO, when fused with FGF21, was able to promote its soluble expression of the latter in E. coli, making it more convenient to purify rFGF21 than previously. This may be a better method to produce rFGF21 for pharmaceutical research and development.",2010 Feb 17,"['Wang, Huiyan', 'Xiao, Yechen', 'Fu, Lianjun', 'Zhao, Hongxin', 'Zhang, Yaofang', 'Wan, Xiaoshan', 'Qin, Yuxia', 'Huang, Yadong', 'Gao, Hongchang', 'Li, Xiaokun']",BMC Biotechnol,,,True
6f94dde3cf8c2776d869b8490fb491d7416088f0,PMC,Surveillance of febrile patients in a district and evaluation of their spatiotemporal associations: a pilot study,http://dx.doi.org/10.1186/1471-2458-10-84,PMC2831836,20170529,CC BY,"BACKGROUND: Fever is an undifferentiated clinical feature that may enhance the sensitivity of syndromic surveillance systems. By studying the spatiotemporal associations of febrile patients, it may allow early detection of case clustering that indicates imminent threat of infectious disease outbreaks in the community. METHODS: We captured consecutive emergency department visits that led to hospitalization in a district hospital in Hong Kong during the period of 12 Sep 2005 to 14 Oct 2005. We recorded demographic data, provisional diagnoses, temperature on presentation and residential location for each patient-episode, and geocoded the residential addresses. We applied Geographical Information System technology to study the geographical distribution these cases, and their associations within a 50-m buffer zone spatially. A case cluster was defined by three or more spatially associated febrile patients within each three consecutive days. RESULTS: One thousand and sixty six patient-episodes were eligible for analysis; 42% of them had fever (>37°C; oral temperature) on presentation. Two hundred and four patient-episodes (19.1%) came from residential care homes for elderly (RCHE). We detected a total of 40 case clusters during the study period. Clustered cases were of older age; 57 (33.3%) were residents of RCHE. We found a median of 3 patients (range: 3 - 8) and time span of 3 days (range: 2 - 8 days) in each cluster. Twenty five clusters had 2 or more patients living in the same building block; 18 of them were from RCHE. CONCLUSIONS: It is technically feasible to perform surveillance on febrile patients and studying their spatiotemporal associations. The information is potentially useful for early detection of impending infectious disease threats.",2010 Feb 20,"['Choi, Kin-wing', 'Wong, Ngai-sze', 'Lee, Lap-yip', 'Lee, Shui-shan']",BMC Public Health,,,True
4b3e454f57edd89563485c04da1df5f95ebd2b5e,PMC,SARS coronavirus protein 7a interacts with human Ap(4)A-hydrolase,http://dx.doi.org/10.1186/1743-422X-7-31,PMC2831879,20144233,CC BY,"The SARS coronavirus (SARS-CoV) open reading frame 7a (ORF 7a) encodes a 122 amino acid accessory protein. It has no significant sequence homology with any other known proteins. The 7a protein is present in the virus particle and has been shown to interact with several host proteins; thereby implicating it as being involved in several pathogenic processes including apoptosis, inhibition of cellular protein synthesis, and activation of p38 mitogen activated protein kinase. In this study we present data demonstrating that the SARS-CoV 7a protein interacts with human Ap(4)A-hydrolase (asymmetrical diadenosine tetraphosphate hydrolase, EC 3.6.1.17). Ap(4)A-hydrolase is responsible for metabolizing the ""allarmone"" nucleotide Ap(4)A and therefore likely involved in regulation of cell proliferation, DNA replication, RNA processing, apoptosis and DNA repair. The interaction between 7a and Ap(4)A-hydrolase was identified using yeast two-hybrid screening. The interaction was confirmed by co-immunoprecipitation from cultured human cells transiently expressing V5-His tagged 7a and HA tagged Ap(4)A-hydrolase. Human tissue culture cells transiently expressing 7a and Ap(4)A-hydrolase tagged with EGFP and Ds-Red2 respectively show these proteins co-localize in the cytoplasm.",2010 Feb 9,"['Vasilenko, Natalia', 'Moshynskyy, Igor', 'Zakhartchouk, Alexander']",Virol J,,,True
f4714dd09f8ab317ec688ba087e67239b2b93367,PMC,Coevolution of activating and inhibitory receptors within mammalian carcinoembryonic antigen families,http://dx.doi.org/10.1186/1741-7007-8-12,PMC2832619,20132533,CC BY,"BACKGROUND: Most rapidly evolving gene families are involved in immune responses and reproduction, two biological functions which have been assigned to the carcinoembryonic antigen (CEA) gene family. To gain insights into evolutionary forces shaping the CEA gene family we have analysed this gene family in 27 mammalian species including monotreme and marsupial lineages. RESULTS: Phylogenetic analysis provided convincing evidence that the primordial CEA gene family in mammals consisted of five genes, including the immune inhibitory receptor-encoding CEACAM1 (CEA-related cell adhesion molecule) ancestor. Our analysis of the substitution rates within the nucleotide sequence which codes for the ligand binding domain of CEACAM1 indicates that the selection for diversification is, perhaps, a consequence of the exploitation of CEACAM1 by a variety of viral and bacterial pathogens as their cellular receptor. Depending on the extent of the amplification of an ancestral CEACAM1, the number of CEACAM1-related genes varies considerably between mammalian species from less than five in lagomorphs to more than 100 in bats. In most analysed species, ITAM (immunoreceptor tyrosine-based activation motifs) or ITAM-like motif-containing proteins exist which contain Ig-V-like, ligand binding domains closely related to that of CEACAM1. Human CEACAM3 is one such protein which can function as a CEACAM1 decoy receptor in granulocytes by mediating the uptake and destruction of specific bacterial pathogens via its ITAM-like motif. The close relationship between CEACAM1 and its ITAM-encoding relatives appears to be maintained by gene conversion and reciprocal recombination. Surprisingly, secreted CEACAMs resembling immunomodulatory CEACAM1-related trophoblast-specific pregnancy-specific glycoproteins (PSGs) found in humans and rodents evolved only in a limited set of mammals. The appearance of PSG-like genes correlates with invasive trophoblast growth in these species. CONCLUSIONS: These phylogenetic studies provide evidence that pathogen/host coevolution and a possible participation in fetal-maternal conflict processes led to a highly species-specific diversity of mammalian CEA gene families.",2010 Feb 4,"['Kammerer, Robert', 'Zimmermann, Wolfgang']",BMC Biol,,,True
f72764a9a0f911eb892cf04752566d6ef4ee54c4,PMC,Binding of Herpes Simplex Virus Type-1 Virions Leads to the Induction of Intracellular Signalling in the Absence of Virus Entry,http://dx.doi.org/10.1371/journal.pone.0009560,PMC2832691,20221426,CC BY,"The envelope of HSV-1 contains a number of glycoproteins, four of which are essential for virus entry. Virus particles lacking gB, gD, gH or gL are entry-defective, although these viruses retain the ability to bind to the plasma membrane via the remaining glycoproteins. Soluble forms of gD have been shown to trigger the nuclear translocation of the NF-κB transcriptional complex in addition to stimulating the production of Type I interferon. By taking advantage of the entry-defective phenotype of glycoprotein-deficient HSV-1 virus particles, the results presented here show that binding of virions to cellular receptors on the plasma membrane is sufficient to stimulate a change in cellular gene expression. Preliminary microarray studies, validated by quantitative real-time PCR, identified the differential expression of cellular genes associated with the NF-κB, PI3K/Akt, Jak/Stat and related Jak/Src pathways by virions lacking gB or gH but not gD. Gene induction occurred at a few particles per cell, corresponding to physiological conditions during primary infection. Reporter assay studies determined that NF-κB transcriptional activity is stimulated within an hour of HSV-1 binding, peaks between two and three hours post-binding and declines to background levels by five hours after induction. The immediate, transient nature of these signalling events suggests that HSV-1 glycoproteins, particularly gD, may alter the cellular environment pre-entry so as to condition the cell for viral replication.",2010 Mar 5,"['MacLeod, Iain J.', 'Minson, Tony']",PLoS One,,,True
9f7729a11b54369146911c3ce8d0d9a299925080,PMC,Binding of Herpes Simplex Virus Type-1 Virions Leads to the Induction of Intracellular Signalling in the Absence of Virus Entry,http://dx.doi.org/10.1371/journal.pone.0009560,PMC2832691,20221426,CC BY,"The envelope of HSV-1 contains a number of glycoproteins, four of which are essential for virus entry. Virus particles lacking gB, gD, gH or gL are entry-defective, although these viruses retain the ability to bind to the plasma membrane via the remaining glycoproteins. Soluble forms of gD have been shown to trigger the nuclear translocation of the NF-κB transcriptional complex in addition to stimulating the production of Type I interferon. By taking advantage of the entry-defective phenotype of glycoprotein-deficient HSV-1 virus particles, the results presented here show that binding of virions to cellular receptors on the plasma membrane is sufficient to stimulate a change in cellular gene expression. Preliminary microarray studies, validated by quantitative real-time PCR, identified the differential expression of cellular genes associated with the NF-κB, PI3K/Akt, Jak/Stat and related Jak/Src pathways by virions lacking gB or gH but not gD. Gene induction occurred at a few particles per cell, corresponding to physiological conditions during primary infection. Reporter assay studies determined that NF-κB transcriptional activity is stimulated within an hour of HSV-1 binding, peaks between two and three hours post-binding and declines to background levels by five hours after induction. The immediate, transient nature of these signalling events suggests that HSV-1 glycoproteins, particularly gD, may alter the cellular environment pre-entry so as to condition the cell for viral replication.",2010 Mar 5,"['MacLeod, Iain J.', 'Minson, Tony']",PLoS One,,,False
02e34b2fe0968cb8a46313fe767858da7e2691b1,PMC,"Candidates in Astroviruses, Seadornaviruses, Cytorhabdoviruses and Coronaviruses for +1 frame overlapping genes accessed by leaky scanning",http://dx.doi.org/10.1186/1743-422X-7-17,PMC2832772,20100346,CC BY,"BACKGROUND: Overlapping genes are common in RNA viruses where they serve as a mechanism to optimize the coding potential of compact genomes. However, annotation of overlapping genes can be difficult using conventional gene-finding software. Recently we have been using a number of complementary approaches to systematically identify previously undetected overlapping genes in RNA virus genomes. In this article we gather together a number of promising candidate new overlapping genes that may be of interest to the community. RESULTS: Overlapping gene predictions are presented for the astroviruses, seadornaviruses, cytorhabdoviruses and coronaviruses (families Astroviridae, Reoviridae, Rhabdoviridae and Coronaviridae, respectively).",2010 Jan 25,"['Firth, Andrew E', 'Atkins, John F']",Virol J,,,True
b9b85a4893f9ed75881adcedbf142098bd7edc93,PMC,Thermal stability and inactivation of hepatitis C virus grown in cell culture,http://dx.doi.org/10.1186/1743-422X-7-40,PMC2834657,20167059,CC BY,"BACKGROUND: Hepatitis C virus (HCV) is a blood-borne flavivirus that infects many millions of people worldwide. Relatively little is known, however, concerning the stability of HCV and reliable procedures for inactivating this virus. METHODS: In the current study, the thermostability of cell culture-derived HCV (HCVcc, JFH-1 strain) under different environmental temperatures (37°C, room temperature, and 4°C) and the ability of heat, UVC light irradiation, and aldehyde and detergent treatments to inactivate HCVcc were evaluated. The infectious titers of treated viral samples were determined by focus-forming unit (FFU) assay using an indirect immunofluorescence assay for HCV NS3 in hepatoma Huh7-25-CD81 cells highly permissive for HCVcc infection. MTT cytotoxicity assay was performed to determine the concentrations of aldehydes or detergents at which they were no longer cytotoxic. RESULTS: HCVcc in culture medium was found to survive 37°C and room temperature (RT, 25 ± 2°C) for 2 and 16 days, respectively, while the virus was relatively stable at 4°C without drastic loss of infectivity for at least 6 weeks. HCVcc in culture medium was sensitive to heat and could be inactivated in 8 and 4 min when incubated at 60°C and 65°C, respectively. However, at 56°C, 40 min were required to eliminate HCVcc infectivity. Addition of normal human serum to HCVcc did not significantly alter viral stability at RT or its susceptibility to heat. UVC light irradiation (wavelength = 253.7 nm) with an intensity of 450 μW/cm(2 )efficiently inactivated HCVcc within 2 min. Exposures to formaldehyde, glutaraldehyde, ionic or nonionic detergents all destroyed HCVcc infectivity effectively, regardless of whether the treatments were conducted in the presence of cell culture medium or human serum. CONCLUSIONS: The results provide quantitative evidence for the potential use of a variety of approaches for inactivating HCV. The ability of HCVcc to survive ambient temperatures warrants precautions in handling and disposing of objects and materials that may have been contaminated with HCV.",2010 Feb 18,"['Song, Hongshuo', 'Li, Jin', 'Shi, Shuang', 'Yan, Ling', 'Zhuang, Hui', 'Li, Kui']",Virol J,,,True
9fdb08f94d250800ca69a84cb21c110adbe1476b,PMC,"New Approaches to Preventing, Diagnosing, and Treating Neonatal Sepsis",http://dx.doi.org/10.1371/journal.pmed.1000213,PMC2834705,20231868,CC BY,Karen Edmond and Anita Zaidi highlight new approaches that could reduce the burden of neonatal sepsis worldwide.,2010 Mar 9,"['Edmond, Karen', 'Zaidi, Anita']",PLoS Med,,,True
af10fafcbc7f54b2c2cf780db5ccf5a2b4a1c985,PMC,Murine Coronavirus Cell Type Dependent Interaction with the Type I Interferon Response,http://dx.doi.org/10.3390/v1030689,PMC2835314,20221421,CC BY,"Coronaviruses infect many species of animal including humans, causing acute and chronic diseases of many organ systems. Murine coronavirus, mouse hepatitis virus (MHV) infection of the mouse, provides animal models for the study of central nervous system disease, including encephalitis and demyelinating diseases such as Multiple Sclerosis and for hepatitis. While there are many studies of the adaptive immune response to MHV, there has until recently been scant information on the type I interferon (IFN) response to MHV. The relationship between MHV and the IFN-α/β response is paradoxical. While the type I IFN response is a crucial aspect of host defense against MHV in its natural host, there is little if any induction of IFN following infection of mouse fibroblast cell lines in vitro. Furthermore, MHV is relatively resistant to the antiviral effects of IFN-α/β in mouse fibroblast cell lines and in human 293T cells. MHV can, under some circumstances, compromise the antiviral effects of IFN signaling. The nucleocapsid protein as well as the nsp1 and nsp3 proteins of MHV has been reported to have IFN antagonist activity. However, in primary cell types such as plasmacytoid dendritic cells (pDC) and macrophages, IFN is induced by MHV infection and an antiviral state is established. Other primary cell types such as neurons, astrocytes and hepatocytes fail to produce IFN following infection and, in vivo, likely depend on IFN produced by pDCs and macrophages for protection from MHV. Thus MHV induction of IFN-α/β and the ability to induce an antiviral state in response to interferon is extremely cell type dependent. IFN induced protection from MHV pathogenesis likely requires the orchestrated activities of several cell types, however, the cell types involved in limiting MHV replication may be different in the liver and in the immune privileged CNS.",2009 Nov 4,"['Rose, Kristine M.', 'Weiss, Susan R.']",Viruses,,,True
0ddcebebb542f8a0905a3cf82a59f404158d3de2,PMC,Simultaneous Detection of CDC Category “A” DNA and RNA Bioterrorism Agents by Use of Multiplex PCR & RT-PCR Enzyme Hybridization Assays,http://dx.doi.org/10.3390/v1030441,PMC2836126,20224751,CC BY,"Assays to simultaneously detect multiple potential agents of bioterrorism are limited. Two multiplex PCR and RT-PCR enzyme hybridization assays (mPCR-EHA, mRT-PCR-EHA) were developed to simultaneously detect many of the CDC category “A” bioterrorism agents. The “Bio T” DNA assay was developed to detect: Variola major (VM), Bacillus anthracis (BA), Yersinia pestis (YP), Francisella tularensis (FT) and Varicella zoster virus (VZV). The “Bio T” RNA assay (mRT-PCR-EHA) was developed to detect: Ebola virus (Ebola), Lassa fever virus (Lassa), Rift Valley fever (RVF), Hantavirus Sin Nombre species (HSN) and dengue virus (serotypes 1–4). Sensitivity and specificity of the 2 assays were tested by using genomic DNA, recombinant plasmid positive controls, RNA transcripts controls, surrogate (spiked) clinical samples and common respiratory pathogens. The analytical sensitivity (limit of detection (LOD)) of the DNA asssay for genomic DNA was 1×10(0)∼1×10(2) copies/mL for BA, FT and YP. The LOD for VZV whole organism was 1×10(−2) TCID(50)/mL. The LOD for recombinant controls ranged from 1×10(2)∼1×10(3)copies/mL for BA, FT, YP and VM. The RNA assay demonstrated LOD for RNA transcript controls of 1×10(4)∼1×10(6) copies/mL without extraction and 1×10(5)∼1×10(6) copies/mL with extraction for Ebola, RVF, Lassa and HSN. The LOD for dengue whole organisms was ∼1×10(−4) dilution for dengue 1 and 2, 1×10(4) LD(50)/mL and 1×10(2) LD(50)/mL for dengue 3 and 4. The LOD without extraction for recombinant plasmid DNA controls was ∼1×10(3) copies/mL (1.5 input copies/reaction) for Ebola, RVF, Lassa and HSN. No cross-reactivity of primers and probes used in both assays was detected with common respiratory pathogens or between targeted analytes. Clinical sensitivity was estimated using 264 surrogate clinical samples tested with the BioT DNA assay and 549 samples tested with the BioT RNA assay. The clinical specificity is 99.6% and 99.8% for BioT DNA assay and BioT RNA assay, respectively. The surrogate sensitivities of these two assays were 100% (95%CI 83–100) for FT, BA (pX02), YP, VM, VZV, dengue 2,3,4 and 95% (95%CI 75–100) for BA (pX01) and dengue 1 using spiked clinical specimens. The specificity of both BioT multiplex assays on spiked specimens was 100% (95% CI 99–100). Compared to other available assays (culture, serology, PCR, etc.) both the BioT DNA mPCR-EHA and BioT RNA mRT-PCR-EHA are rapid, sensitive and specific assays for detecting many category “A” Bioterrorism agents using a standard thermocycler.",2009 Oct 20,"['He, Jie', 'Kraft, Andrea J.', 'Fan, Jiang', 'Van Dyke, Meredith', 'Wang, Lihua', 'Bose, Michael E.', 'Khanna, Marilyn', 'Metallo, Jacob A.', 'Henrickson, Kelly J.']",Viruses,,,True
f8243fd9214e2e45a222a43aad977d882f17e1e9,PMC,Computational analysis and determination of a highly conserved surface exposed segment in H5N1 avian flu and H1N1 swine flu neuraminidase,http://dx.doi.org/10.1186/1472-6807-10-6,PMC2836360,20170556,CC BY,"BACKGROUND: Catalytic activity of influenza neuraminidase (NA) facilitates elution of progeny virions from infected cells and prevents their self-aggregation mediated by the catalytic site located in the body region. Research on the active site of the molecule has led to development of effective inhibitors like oseltamivir, zanamivir etc, but the high rate of mutation and interspecies reassortment in viral sequences and the recent reports of oseltamivir resistant strains underlines the importance of determining additional target sites for developing future antiviral compounds. In a recent computational study of 173 H5N1 NA gene sequences we had identified a 50-base highly conserved region in 3'-terminal end of the NA gene. RESULTS: We extend the graphical and numerical analyses to a larger number of H5N1 NA sequences (514) and H1N1 swine flu sequences (425) accessed from GenBank. We use a 2D graphical representation model for the gene sequences and a Graphical Sliding Window Method (GSWM) for protein sequences scanning the sequences as a block of 16 amino acids at a time. Using a protein sequence descriptor defined in our model, the protein sliding scan method allowed us to compare the different strains for block level variability, which showed significant statistical correlation to average solvent accessibility of the residue blocks; single amino acid position variability results in no correlation, indicating the impact of stretch variability in chemical environment. Close to the C-terminal end the GSWM showed less descriptor-variability with increased average solvent accessibility (ASA) that is also supported by conserved predicted secondary structure of 3' terminal RNA and visual evidence from 3D crystallographic structure. CONCLUSION: The identified terminal segment, strongly conserved in both RNA and protein sequences, is especially significant as it is surface exposed and structural chemistry reveals the probable role of this stretch in tetrameric stabilization. It could also participate in other biological processes associated with conserved surface residues. A RNA double hairpin secondary structure found in this segment in a majority of the H5N1 strains also supports this observation. In this paper we propose this conserved region as a probable site for designing inhibitors for broad-spectrum pandemic control of flu viruses with similar NA structure.",2010 Feb 22,"['Ghosh, Ambarnil', 'Nandy, Ashesh', 'Nandy, Papiya']",BMC Struct Biol,,,True
89d0e2ff08a2a140032fffa032af6dffb1ddae07,PMC,Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features,http://dx.doi.org/10.1371/journal.pone.0009603,PMC2836373,20300175,CC BY,"BACKGROUND: Study of drug-target interaction networks is an important topic for drug development. It is both time-consuming and costly to determine compound-protein interactions or potential drug-target interactions by experiments alone. As a complement, the in silico prediction methods can provide us with very useful information in a timely manner. METHODS/PRINCIPAL FINDINGS: To realize this, drug compounds are encoded with functional groups and proteins encoded by biological features including biochemical and physicochemical properties. The optimal feature selection procedures are adopted by means of the mRMR (Maximum Relevance Minimum Redundancy) method. Instead of classifying the proteins as a whole family, target proteins are divided into four groups: enzymes, ion channels, G-protein- coupled receptors and nuclear receptors. Thus, four independent predictors are established using the Nearest Neighbor algorithm as their operation engine, with each to predict the interactions between drugs and one of the four protein groups. As a result, the overall success rates by the jackknife cross-validation tests achieved with the four predictors are 85.48%, 80.78%, 78.49%, and 85.66%, respectively. CONCLUSION/SIGNIFICANCE: Our results indicate that the network prediction system thus established is quite promising and encouraging.",2010 Mar 11,"['He, Zhisong', 'Zhang, Jian', 'Shi, Xiao-He', 'Hu, Le-Le', 'Kong, Xiangyin', 'Cai, Yu-Dong', 'Chou, Kuo-Chen']",PLoS One,,,True
345180770287ab9188e2dcfa2fd2ba0cd58214bb,PMC,Associations between attributes of live poultry trade and HPAI H5N1 outbreaks: a descriptive and network analysis study in northern Vietnam,http://dx.doi.org/10.1186/1746-6148-6-10,PMC2837645,20175881,CC BY,"BACKGROUND: The structure of contact between individuals plays an important role in the incursion and spread of contagious diseases in both human and animal populations. In the case of avian influenza, the movement of live birds is a well known risk factor for the geographic dissemination of the virus among poultry flocks. Live bird markets (LBM's) contribute to the epidemiology of avian influenza due to their demographic characteristics and the presence of HPAI H5N1 virus lineages. The relationship between poultry producers and live poultry traders (LPT's) that operate in LBM's has not been adequately documented in HPAI H5N1-affected SE Asian countries. The aims of this study were to document and study the flow of live poultry in a poultry trade network in northern Vietnam, and explore its potential role in the risk for HPAI H5N1 during 2003 to 2006. RESULTS: Our results indicate that LPT's trading for less than a year and operating at retail markets are more likely to source poultry from flocks located in communes with a past history of HPAI H5N1 outbreaks during 2003 to 2006 than LPT's trading longer than a year and operating at wholesale markets. The results of the network analysis indicate that LPT's tend to link communes of similar infection status. CONCLUSIONS: Our study provides evidence which can be used for informing policies aimed at encouraging more biosecure practices of LPT's operating at authorised LBM's. The results suggest that LPT's play a role in HPAI H5N1 transmission and may contribute to perpetuating HPAI H5N1 virus circulation amongst certain groups of communes. The impact of current disease prevention and control interventions could be enhanced by disseminating information about outbreak risk and the implementation of a formal data recording scheme at LBM's for all incoming and outgoing LPT's.",2010 Feb 22,"['Soares Magalhães, Ricardo J', 'Ortiz-Pelaez, Angel', 'Thi, Kim Lan Lai', 'Dinh, Quoc Hoang', 'Otte, Joachim', 'Pfeiffer, Dirk U']",BMC Vet Res,,,True
73d7ae5e79b6ba07548cf38ddcaa2979bee6916b,PMC,Origin of measles virus: divergence from rinderpest virus between the 11(th )and 12(th )centuries,http://dx.doi.org/10.1186/1743-422X-7-52,PMC2838858,20202190,CC BY,"Measles, caused by measles virus (MeV), is a common infection in children. MeV is a member of the genus Morbillivirus and is most closely related to rinderpest virus (RPV), which is a pathogen of cattle. MeV is thought to have evolved in an environment where cattle and humans lived in close proximity. Understanding the evolutionary history of MeV could answer questions related to divergence times of MeV and RPV. We investigated divergence times using relaxed clock Bayesian phylogenetics. Our estimates reveal that MeV had an evolutionary rate of 6.0 - 6.5 × 10(-4 )substitutions/site/year. It was concluded that the divergence time of the most recent common ancestor of current MeV was the early 20(th )century. And, divergence between MeV and RPV occurred around the 11(th )to 12(th )centuries. The result was unexpected because emergence of MeV was previously considered to have occurred in the prehistoric age. MeV may have originated from virus of non-human species and caused emerging infectious diseases around the 11(th )to 12(th )centuries. In such cases, investigating measles would give important information about the course of emerging infectious diseases.",2010 Mar 4,"['Furuse, Yuki', 'Suzuki, Akira', 'Oshitani, Hitoshi']",Virol J,,,True
31042ccf8374ad96d39d8156d9e2ced042734ba9,PMC,High-throughput detection of mutations responsible for childhood hearing loss using resequencing microarrays,http://dx.doi.org/10.1186/1472-6750-10-10,PMC2841091,20146813,CC BY,"BACKGROUND: Despite current knowledge of mutations in 45 genes that can cause nonsyndromic sensorineural hearing loss (SNHL), no unified clinical test has been developed that can comprehensively detect mutations in multiple genes. We therefore designed Affymetrix resequencing microarrays capable of resequencing 13 genes mutated in SNHL (GJB2, GJB6, CDH23, KCNE1, KCNQ1, MYO7A, OTOF, PDS, MYO6, SLC26A5, TMIE, TMPRSS3, USH1C). We present results from hearing loss arrays developed in two different research facilities and highlight some of the approaches we adopted to enhance the applicability of resequencing arrays in a clinical setting. RESULTS: We leveraged sequence and intensity pattern features responsible for diminished coverage and accuracy and developed a novel algorithm, sPROFILER, which resolved >80% of no-calls from GSEQ and allowed 99.6% (range: 99.2-99.8%) of sequence to be called, while maintaining overall accuracy at >99.8% based upon dideoxy sequencing comparison. CONCLUSIONS: Together, these findings provide insight into critical issues for disease-centered resequencing protocols suitable for clinical application and support the use of array-based resequencing technology as a valuable molecular diagnostic tool for pediatric SNHL and other genetic diseases with substantial genetic heterogeneity.",2010 Feb 10,"['Kothiyal, Prachi', 'Cox, Stephanie', 'Ebert, Jonathan', 'Husami, Ammar', 'Kenna, Margaret A', 'Greinwald, John H', 'Aronow, Bruce J', 'Rehm, Heidi L']",BMC Biotechnol,,,True
4faf1ac964c605b384dda60bc37df300766401b9,PMC,NSs Encoded by Groundnut Bud Necrosis Virus Is a Bifunctional Enzyme,http://dx.doi.org/10.1371/journal.pone.0009757,PMC2841200,20305786,CC BY,"Groundnut bud necrosis virus (GBNV), a member of genus Tospovirus in the family Bunyaviridae, infects a large number of leguminosae and solanaceae plants in India. With a view to elucidate the function of nonstructural protein, NSs encoded by the small RNA genome (S RNA), the NSs protein of GBNV- tomato (Karnataka) [1] was over-expressed in E. coli and purified by Ni-NTA chromatography. The purified rNSs protein exhibited an RNA stimulated NTPase activity. Further, this activity was metal ion dependent and was inhibited by adenosine 5′ (β, γ imido) triphosphate, an ATP analog. The rNSs could also hydrolyze dATP. Interestingly, in addition to the NTPase and dATPase activities, the rNSs exhibited ATP independent 5′ RNA/DNA phosphatase activity that was completely inhibited by AMP. The 5′ α phosphate could be removed from ssDNA, ssRNA, dsDNA and dsRNA thus confirming that rNSs has a novel 5′ α phosphatase activity. K189A mutation in the Walker motif A (GxxxxGKT) resulted in complete loss of ATPase activity, but the 5′ phosphatase activity was unaffected. On the other hand, D159A mutation in the Walker motif B (DExx) resulted in partial loss of both the activities. These results demonstrate for the first time that NSs is a bifunctional enzyme, which could participate in viral movement, replication or in suppression of the host defense mechanism.",2010 Mar 18,"['Lokesh, Bhushan', 'Rashmi, Panigrahi R.', 'Amruta, Bhat S.', 'Srisathiyanarayanan, Dharmaiah', 'Murthy, Mathur R. N.', 'Savithri, Handanahal S.']",PLoS One,,,True
05a94d5f5083ff58320c659cd519536d3e6aa4a3,PMC,A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry,http://dx.doi.org/10.1371/journal.ppat.1000808,PMC2841620,20333243,CC BY,"Viruses use cellular machinery to enter and infect cells. In this study we address the cell entry mechanisms of nonenveloped adenoviruses (Ads). We show that protein VI, an internal capsid protein, is rapidly exposed after cell surface attachment and internalization and remains partially associated with the capsid during intracellular transport. We found that a PPxY motif within protein VI recruits Nedd4 E3 ubiquitin ligases to bind and ubiquitylate protein VI. We further show that this PPxY motif is involved in rapid, microtubule-dependent intracellular movement of protein VI. Ads with a mutated PPxY motif can efficiently escape endosomes but are defective in microtubule-dependent trafficking toward the nucleus. Likewise, depletion of Nedd4 ligases attenuates nuclear accumulation of incoming Ad particles and infection. Our data provide the first evidence that virus-encoded PPxY motifs are required during virus entry, which may be of significance for several other pathogens.",2010 Mar 19,"['Wodrich, Harald', 'Henaff, Daniel', 'Jammart, Baptist', 'Segura-Morales, Carolina', 'Seelmeir, Sigrid', 'Coux, Olivier', 'Ruzsics, Zsolt', 'Wiethoff, Christopher M.', 'Kremer, Eric J.']",PLoS Pathog,,,True
73939a4a3eff4347a97d4dbe05c46a3a1fc08a82,PMC,University life and pandemic influenza: Attitudes and intended behaviour of staff and students towards pandemic (H1N1) 2009,http://dx.doi.org/10.1186/1471-2458-10-130,PMC2841672,20226093,CC BY,"BACKGROUND: In a pandemic young adults are more likely to be infected, increasing the potential for Universities to be explosive disease outbreak centres. Outbreak management is essential to reduce the impact in both the institution and the surrounding community. Through the use of an online survey, we aimed to measure the perceptions and responses of staff and students towards pandemic (H1N1) 2009 at a major university in Sydney, Australia. METHODS: The survey was available online from 29 June to 30 September 2009. The sample included academic staff, general staff and students of the University. RESULTS: A total of 2882 surveys were completed. Nearly all respondents (99.6%, 2870/2882) were aware of the Australian pandemic situation and 64.2% (1851/2882) reported either ""no anxiety"" or ""disinterest."" Asian-born respondents were significantly (p < 0.001) more likely to believe that the pandemic was serious compared to respondents from other regions. 75.9% (2188/2882) of respondents had not made any lifestyle changes as a result of the pandemic. Most respondents had not adopted any specific behaviour change, and only 20.8% (600/2882) had adopted the simplest health behaviour, i.e. hand hygiene. Adoption of a specific behaviour change was linked to anxiety and Asian origin. Students were more likely to attend the university if unwell compared with staff members. Positive responses from students strongly indicate the potential for expanding online teaching and learning resources for continuing education in disaster settings. Willingness to receive the pandemic vaccine was associated with seasonal influenza vaccination uptake over the previous 3 years. CONCLUSIONS: Responses to a pandemic are subject to change in its pre-, early and mid-outbreak stages. Lessons for these institutions in preparation for a second wave and future disease outbreaks include the need to promote positive public health behaviours amongst young people and students.",2010 Mar 14,"['Van, Debbie', 'McLaws, Mary-Louise', 'Crimmins, Jacinta', 'MacIntyre, C Raina', 'Seale, Holly']",BMC Public Health,,,True
91b6e6a867abca446f467eeadcdbbfda198af6a1,PMC,Plug-and-play inference for disease dynamics: measles in large and small populations as a case study,http://dx.doi.org/10.1098/rsif.2009.0151,PMC2842609,19535416,CC BY,"Statistical inference for mechanistic models of partially observed dynamic systems is an active area of research. Most existing inference methods place substantial restrictions upon the form of models that can be fitted and hence upon the nature of the scientific hypotheses that can be entertained and the data that can be used to evaluate them. In contrast, the so-called plug-and-play methods require only simulations from a model and are thus free of such restrictions. We show the utility of the plug-and-play approach in the context of an investigation of measles transmission dynamics. Our novel methodology enables us to ask and answer questions that previous analyses have been unable to address. Specifically, we demonstrate that plug-and-play methods permit the development of a modelling and inference framework applicable to data from both large and small populations. We thereby obtain novel insights into the nature of heterogeneity in mixing and comment on the importance of including extra-demographic stochasticity as a means of dealing with environmental stochasticity and model misspecification. Our approach is readily applicable to many other epidemiological and ecological systems.",2010 Feb 6,"['He, Daihai', 'Ionides, Edward L.', 'King, Aaron A.']",J R Soc Interface,,,True
f2ab1be1bbd80c0f102714fdc90597af2739442c,PMC,"Comparative Efficacy of Hemagglutinin, Nucleoprotein, and Matrix 2 Protein Gene-Based Vaccination against H5N1 Influenza in Mouse and Ferret",http://dx.doi.org/10.1371/journal.pone.0009812,PMC2843722,20352112,CC0,"Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products. The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes. Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus. In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA. However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased. To explore this question in a model relevant to human disease, ferrets were immunized with DNA/rAd5 vaccines encoding NP, M2, HA, NP+M2 or HA+NP+M2. Only HA or HA+NP+M2 vaccination conferred protection against a stringent virus challenge. Therefore, while gene-based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets. These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge.",2010 Mar 23,"['Rao, Srinivas S.', 'Kong, Wing-Pui', 'Wei, Chih-Jen', 'Van Hoeven, Neal', 'Gorres, J. Patrick', 'Nason, Martha', 'Andersen, Hanne', 'Tumpey, Terrence M.', 'Nabel, Gary J.']",PLoS One,,,True
94cd1610fd21b8fc289d65a96973216217a955dd,PMC,"Awareness, attitudes, and practices related to the swine influenza pandemic among the Saudi public",http://dx.doi.org/10.1186/1471-2334-10-42,PMC2844401,20187976,CC BY,"BACKGROUND: During an infectious disease outbreak, it is critical to learn as much as possible about the concerns, knowledge, attitudes, and behavior of the public. Such information can be crucial to the improvement of communication efforts by public health officials and clinicians. The aim of this study was to identify awareness, attitudes, and practices related to influenza A (H1N1) among the Saudi public. METHODS: A cross-sectional study of 1,548 adult subjects recruited from various shopping malls in Riyadh and Jeddah was conducted. All of the subjects were interviewed using a questionnaire that tested their knowledge, attitudes, and use of precautionary measures in relation to the H1N1 influenza pandemic. RESULTS: More than half (54.3%, 840/1548) of the participants showed high concern, 43.7%(677/1548) showed a low level of knowledge, and 60.8%(941/1548) had taken minimal or no precautionary measures. After adjusting for other variables, education level was the only significant predictor of the level of concern (p < 0.001), while greater precautionary measures were taken by participants who were male (p < 0.001), older (p = 0.047), better educated (p = 0.04), and more knowledgeable (p < 0.001). More than one-third (38.3%) of participants were not convinced that the MOH reports about the disease were true, and only 16.1% of the participants reported receiving information from health providers. CONCLUSIONS: High concern did not translate into a higher compliance with precautionary recommendations, possibly due to the low level of knowledge about the disease among the public. Frequent communication between physicians and the public is recommended to help dispel myths about the disease and to spread better information about the role that the public can play in limiting the spread of the disease.",2010 Feb 28,"['Balkhy, Hanan H', 'Abolfotouh, Mostafa A', 'Al-Hathlool, Rawabi H', 'Al-Jumah, Mohammad A']",BMC Infect Dis,,,True
bf3ec9cb72885b43173311a92e237c5417a53883,PMC,The Impact of Contact Tracing in Clustered Populations,http://dx.doi.org/10.1371/journal.pcbi.1000721,PMC2845652,20361048,CC BY,"The tracing of potentially infectious contacts has become an important part of the control strategy for many infectious diseases, from early cases of novel infections to endemic sexually transmitted infections. Here, we make use of mathematical models to consider the case of partner notification for sexually transmitted infection, however these models are sufficiently simple to allow more general conclusions to be drawn. We show that, when contact network structure is considered in addition to contact tracing, standard “mass action” models are generally inadequate. To consider the impact of mutual contacts (specifically clustering) we develop an improvement to existing pairwise network models, which we use to demonstrate that ceteris paribus, clustering improves the efficacy of contact tracing for a large region of parameter space. This result is sometimes reversed, however, for the case of highly effective contact tracing. We also develop stochastic simulations for comparison, using simple re-wiring methods that allow the generation of appropriate comparator networks. In this way we contribute to the general theory of network-based interventions against infectious disease.",2010 Mar 26,"['House, Thomas', 'Keeling, Matt J.']",PLoS Comput Biol,,,True
de33cc55be6bb27a8f52e33fe21836c670252e28,PMC,Serological Profiling of a Candida albicans Protein Microarray Reveals Permanent Host-Pathogen Interplay and Stage-Specific Responses during Candidemia,http://dx.doi.org/10.1371/journal.ppat.1000827,PMC2845659,20361054,CC0,"Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection.",2010 Mar 26,"['Mochon, A. Brian', 'Ye, Jin', 'Kayala, Matthew A.', 'Wingard, John R.', 'Clancy, Cornelius J.', 'Nguyen, M. Hong', 'Felgner, Philip', 'Baldi, Pierre', 'Liu, Haoping']",PLoS Pathog,,,True
808bc72c8ec0d2cb6bc74492c1155f0528057417,PMC,Serological Profiling of a Candida albicans Protein Microarray Reveals Permanent Host-Pathogen Interplay and Stage-Specific Responses during Candidemia,http://dx.doi.org/10.1371/journal.ppat.1000827,PMC2845659,20361054,CC0,"Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection.",2010 Mar 26,"['Mochon, A. Brian', 'Ye, Jin', 'Kayala, Matthew A.', 'Wingard, John R.', 'Clancy, Cornelius J.', 'Nguyen, M. Hong', 'Felgner, Philip', 'Baldi, Pierre', 'Liu, Haoping']",PLoS Pathog,,,False
28ac05c52a6ce75d7a7b9ae00a335dbb7c1d4883,PMC,Serological Profiling of a Candida albicans Protein Microarray Reveals Permanent Host-Pathogen Interplay and Stage-Specific Responses during Candidemia,http://dx.doi.org/10.1371/journal.ppat.1000827,PMC2845659,20361054,CC0,"Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection.",2010 Mar 26,"['Mochon, A. Brian', 'Ye, Jin', 'Kayala, Matthew A.', 'Wingard, John R.', 'Clancy, Cornelius J.', 'Nguyen, M. Hong', 'Felgner, Philip', 'Baldi, Pierre', 'Liu, Haoping']",PLoS Pathog,,,False
f7c515de412154ba8b4e23343ce1d03ec897cc77,PMC,Serological Profiling of a Candida albicans Protein Microarray Reveals Permanent Host-Pathogen Interplay and Stage-Specific Responses during Candidemia,http://dx.doi.org/10.1371/journal.ppat.1000827,PMC2845659,20361054,CC0,"Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection.",2010 Mar 26,"['Mochon, A. Brian', 'Ye, Jin', 'Kayala, Matthew A.', 'Wingard, John R.', 'Clancy, Cornelius J.', 'Nguyen, M. Hong', 'Felgner, Philip', 'Baldi, Pierre', 'Liu, Haoping']",PLoS Pathog,,,False
e68377f2ea4468c026ad36b35be9f08f48c9a24b,PMC,Serological Profiling of a Candida albicans Protein Microarray Reveals Permanent Host-Pathogen Interplay and Stage-Specific Responses during Candidemia,http://dx.doi.org/10.1371/journal.ppat.1000827,PMC2845659,20361054,CC0,"Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection.",2010 Mar 26,"['Mochon, A. Brian', 'Ye, Jin', 'Kayala, Matthew A.', 'Wingard, John R.', 'Clancy, Cornelius J.', 'Nguyen, M. Hong', 'Felgner, Philip', 'Baldi, Pierre', 'Liu, Haoping']",PLoS Pathog,,,False
2a71668dd2b73cbbeb5005a2905688ed276603a9,PMC,Searching for the elusive typhoid diagnostic,http://dx.doi.org/10.1186/1471-2334-10-45,PMC2846943,20205702,CC BY,"Typhoid (enteric) fever is still a common disease in many developing countries but current diagnostic tests are inadequate. Studies on pathogenesis and genomics have provided new insight into the organisms that cause enteric fever. Better understanding of the microorganisms explains, in part, why our current typhoid methodologies are limited in their diagnostic information and why developing new strategies may be a considerable challenge. Here we discuss the current position of typhoid diagnostics, highlight the need for technological improvements and suggest potential ways of advancing this area.",2010 Mar 5,"['Baker, Stephen', 'Favorov, Michael', 'Dougan, Gordon']",BMC Infect Dis,,,True
7e9494784505c616553ef19805fb9dd82c89dea9,PMC,"A comparative epidemiologic analysis of SARS in Hong Kong, Beijing and Taiwan",http://dx.doi.org/10.1186/1471-2334-10-50,PMC2846944,20205928,CC BY,"BACKGROUND: The 2002-2003 Severe Acute Respiratory Syndrome (SARS) outbreak infected 8,422 individuals leading to 916 deaths around the world. However, there have been few epidemiological studies of SARS comparing epidemiologic features across regions. The aim of this study is to identify similarities and differences in SARS epidemiology in three populations with similar host and viral genotype. METHODS: We present a comparative epidemiologic analysis of SARS, based on an integrated dataset with 3,336 SARS patients from Hong Kong, Beijing and Taiwan, epidemiological and clinical characteristics such as incubation, onset-to-admission, onset-to-discharge and onset-to-death periods, case fatality ratios (CFRs) and presenting symptoms are described and compared between regions. We further explored the influence of demographic and clinical variables on the apparently large differences in CFRs between the three regions. RESULTS: All three regions showed similar incubation periods and progressive shortening of the onset-to-admission interval through the epidemic. Adjusted for sex, health care worker status and nosocomial setting, older age was associated with a higher fatality, with adjusted odds ratio (AOR): 2.10 (95% confidence interval: 1.45, 3.04) for those aged 51-60; AOR: 4.57 (95% confidence interval: 3.32, 7.30) for those aged above 60 compared to those aged 41-50 years. Presence of pre-existing comorbid conditions was also associated with greater mortality (AOR: 1.74; 95% confidence interval: 1.36, 2.21). CONCLUSION: The large discrepancy in crude fatality ratios across the three regions can only be partly explained by epidemiological and clinical heterogeneities. Our findings underline the importance of a common data collection platform, especially in an emerging epidemic, in order to identify and explain consistencies and differences in the eventual clinical and public health outcomes of infectious disease outbreaks, which is becoming increasingly important in our highly interconnected world.",2010 Mar 6,"['Lau, Eric HY', 'Hsiung, C Agnes', 'Cowling, Benjamin J', 'Chen, Chang-Hsun', 'Ho, Lai-Ming', 'Tsang, Thomas', 'Chang, Chiu-Wen', 'Donnelly, Christl A', 'Leung, Gabriel M']",BMC Infect Dis,,,True
2a8a6ddd84f0c80ce33fed8960c3201c08e56854,PMC,Nucleolar localization of influenza A NS1: striking differences between mammalian and avian cells,http://dx.doi.org/10.1186/1743-422X-7-63,PMC2847567,20236536,CC BY,"In mammalian cells, nucleolar localization of influenza A NS1 requires the presence of a C-terminal nucleolar localization signal. This nucleolar localization signal is present only in certain strains of influenza A viruses. Therefore, only certain NS1 accumulate in the nucleolus of mammalian cells. In contrast, we show that all NS1 tested in this study accumulated in the nucleolus of avian cells even in the absence of the above described C-terminal nucleolar localization signal. Thus, nucleolar localization of NS1 in avian cells appears to rely on a different nucleolar localization signal that is more conserved among influenza virus strains.",2010 Mar 17,"['Volmer, Romain', 'Mazel-Sanchez, Beryl', 'Volmer, Christelle', 'Soubies, Sébastien M', 'Guérin, Jean-Luc']",Virol J,,,True
846f108dcf44ed854491112e1de0c86b5193cb86,PMC,Self-reported anticipated compliance with physician advice to stay home during pandemic (H1N1) 2009: Results from the 2009 Queensland Social Survey,http://dx.doi.org/10.1186/1471-2458-10-138,PMC2847980,20233450,CC BY,"BACKGROUND: One strategy available to public health officials during a pandemic is physician recommendations for isolation of infected individuals. This study was undertaken during the height of the Australian pandemic (H1N1) 2009 outbreak to measure self-reported willingness to comply with physician recommendations to stay home for seven days, and to compare responses for the current strain of pandemic influenza, avian influenza, seasonal influenza, and the common cold. METHODS: Data were collected as part of the Queensland Social Survey (QSS) 2009, which consisted of a standardized introduction, 37 demographic questions, and research questions incorporated through a cost-sharing arrangement. Four questions related to respondents' anticipated compliance with a physician's advice to stay home if they had a common cold, seasonal influenza, pandemic (H1N1) 2009 influenza or avian influenza were incorporated into QSS 2009, with responses recorded using a balanced Likert scale ranging from ""very unlikely"" to ""very likely."" Discordance between responses for different diseases was analysed using McNemar's test. Associations between demographic variables and anticipated compliance were analysed using Pearson's chi-square or chi-square for linear-by-linear association, and confirmed using multivariate logistic regression; p < 0.05 was used to establish statistical significance. RESULTS: Self-reported anticipated compliance increased from 59.9% for the common cold to 71.3% for seasonal influenza (p < .001), and to 95.0% for pandemic (H1N1) 2009 influenza and 94.7% for avian influenza (p < 0.001 for both versus seasonal influenza). Anticipated compliance did not differ for pandemic (H1N1) 2009 and avian influenza (p = 0.815). Age and sex were both associated with anticipated compliance in the setting of seasonal influenza and the common cold. Notably, 27.1% of health and community service workers would not comply with physician advice to stay home for seasonal influenza. CONCLUSIONS: Ninety-five percent of people report they would comply with a physicians' advice to stay home for seven days if they are diagnosed with pandemic (H1N1) 2009 or avian influenza, but only 71% can be expected to comply in the setting of seasonal influenza and fewer still can be expected to comply if they are diagnosed with a common cold. Sub-populations that might be worthwhile targets for public health messages aimed at increasing the rate of self-imposed isolation for seasonal influenza include males, younger people, and healthcare workers.",2010 Mar 16,"['Brown, Lawrence H', 'Aitken, Peter', 'Leggat, Peter A', 'Speare, Richard']",BMC Public Health,,,True
50aa060bb87a548227b5b972c63920faef016f05,PMC,"Healthcare workers and health care-associated infections: knowledge, attitudes, and behavior in emergency departments in Italy",http://dx.doi.org/10.1186/1471-2334-10-35,PMC2848042,20178573,CC BY,"BACKGROUND: This survey assessed knowledge, attitudes, and compliance regarding standard precautions about health care-associated infections (HAIs) and the associated determinants among healthcare workers (HCWs) in emergency departments in Italy. METHODS: An anonymous questionnaire, self-administered by all HCWs in eight randomly selected non-academic acute general public hospitals, comprised questions on demographic and occupational characteristics; knowledge about the risks of acquiring and/or transmitting HAIs from/to a patient and standard precautions; attitudes toward guidelines and risk perceived of acquiring a HAI; practice of standard precautions; and sources of information. RESULTS: HCWs who know the risk of acquiring Hepatitis C (HCV) and Human Immunodeficiency Virus (HIV) from a patient were in practice from less years, worked fewer hours per week, knew that a HCW can transmit HCV and HIV to a patient, knew that HCV and HIV infections can be serious, and have received information from educational courses and scientific journals. Those who know that gloves, mask, protective eyewear, and hands hygiene after removing gloves are control measures were nurses, provided care to fewer patients, knew that HCWs' hands are vehicle for transmission of nosocomial pathogens, did not know that a HCW can transmit HCV and HIV to a patient, and have received information from educational courses and scientific journals. Being a nurse, knowing that HCWs' hands are vehicle for transmission of nosocomial pathogens, obtaining information from educational courses and scientific journals, and needing information were associated with a higher perceived risk of acquiring a HAI. HCWs who often or always used gloves and performed hands hygiene measures after removing gloves were nurses, provided care to fewer patients, and knew that hands hygiene after removing gloves was a control measure. CONCLUSIONS: HCWs have high knowledge, positive attitudes, but low compliance concerning standard precautions. Nurses had higher knowledge, perceived risk, and appropriate HAIs' control measures than physicians and HCWs answered correctly and used appropriately control measures if have received information from educational courses and scientific journals.",2010 Feb 23,"['Parmeggiani, Cristiana', 'Abbate, Rossella', 'Marinelli, Paolo', 'Angelillo, Italo F']",BMC Infect Dis,,,True
140cdf5d99f486ccd0346d07cad3fa66b2567c42,PMC,Rapid Accumulation of Virulent Rift Valley Fever Virus in Mice from an Attenuated Virus Carrying a Single Nucleotide Substitution in the M RNA,http://dx.doi.org/10.1371/journal.pone.0009986,PMC2848673,20376320,CC BY,"BACKGROUND: Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, is a negative-stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, while in livestock it causes fever and high abortion rates. METHODOLOGY/PRINCIPAL FINDINGS: Sequence analysis showed that a wild-type RVFV ZH501 preparation consisted of two major viral subpopulations, with a single nucleotide heterogeneity at nucleotide 847 of M segment (M847); one had a G residue at M847 encoding glycine in a major viral envelope Gn protein, while the other carried A residue encoding glutamic acid at the corresponding site. Two ZH501-derived viruses, rZH501-M847-G and rZH501-M847-A, carried identical genomic sequences, except that the former and the latter had G and A, respectively, at M847 were recovered by using a reverse genetics system. Intraperitoneal inoculation of rZH501-M847-A into mice caused a rapid and efficient viral accumulation in the sera, livers, spleens, kidneys and brains, and killed most of the mice within 8 days, whereas rZH501-M847-G caused low viremia titers, did not replicate as efficiently as did rZH501-M847-A in these organs, and had attenuated virulence to mice. Remarkably, as early as 2 days postinfection with rZH501-M847-G, the viruses carrying A at M847 emerged and became the major virus population thereafter, while replicating viruses retained the input A residue at M847 in rZH501-M847-A-infected mice. CONCLUSIONS/SIGNIFICANCE: These data demonstrated that the single nucleotide substitution in the Gn protein substantially affected the RVFV mouse virulence and that a virus population carrying the virulent viral genotype quickly emerged and became the major viral population within a few days in mice that were inoculated with the attenuated virus.",2010 Apr 1,"['Morrill, John C.', 'Ikegami, Tetsuro', 'Yoshikawa-Iwata, Naoko', 'Lokugamage, Nandadeva', 'Won, Sungyong', 'Terasaki, Kaori', 'Zamoto-Niikura, Aya', 'Peters, C. J.', 'Makino, Shinji']",PLoS One,,,True
5b454b34b6611cd015799280a78b9fed001068cb,PMC,An optimal control theory approach to non-pharmaceutical interventions,http://dx.doi.org/10.1186/1471-2334-10-32,PMC2850906,20170501,CC BY,"BACKGROUND: Non-pharmaceutical interventions (NPI) are the first line of defense against pandemic influenza. These interventions dampen virus spread by reducing contact between infected and susceptible persons. Because they curtail essential societal activities, they must be applied judiciously. Optimal control theory is an approach for modeling and balancing competing objectives such as epidemic spread and NPI cost. METHODS: We apply optimal control on an epidemiologic compartmental model to develop triggers for NPI implementation. The objective is to minimize expected person-days lost from influenza related deaths and NPI implementations for the model. We perform a multivariate sensitivity analysis based on Latin Hypercube Sampling to study the effects of input parameters on the optimal control policy. Additional studies investigated the effects of departures from the modeling assumptions, including exponential terminal time and linear NPI implementation cost. RESULTS: An optimal policy is derived for the control model using a linear NPI implementation cost. Linear cost leads to a ""bang-bang"" policy in which NPIs are applied at maximum strength when certain state criteria are met. Multivariate sensitivity analyses are presented which indicate that NPI cost, death rate, and recovery rate are influential in determining the policy structure. Further death rate, basic reproductive number and recovery rate are the most influential in determining the expected cumulative death. When applying the NPI policy, the cumulative deaths under exponential and gamma terminal times are close, which implies that the outcome of applying the ""bang-bang"" policy is insensitive to the exponential assumption. Quadratic cost leads to a multi-level policy in which NPIs are applied at varying strength levels, again based on certain state criteria. Results indicate that linear cost leads to more costly implementation resulting in fewer deaths. CONCLUSIONS: The application of optimal control theory can provide valuable insight to developing effective control strategies for pandemic. Our findings highlight the importance of establishing a sensitive and timely surveillance system for pandemic preparedness.",2010 Feb 19,"['Lin, Feng', 'Muthuraman, Kumar', 'Lawley, Mark']",BMC Infect Dis,,,True
476c677579fa461c4fbe5822f1df9a687a6d8928,PMC,Dynamics and Control of Diseases in Networks with Community Structure,http://dx.doi.org/10.1371/journal.pcbi.1000736,PMC2851561,20386735,CC BY,"The dynamics of infectious diseases spread via direct person-to-person transmission (such as influenza, smallpox, HIV/AIDS, etc.) depends on the underlying host contact network. Human contact networks exhibit strong community structure. Understanding how such community structure affects epidemics may provide insights for preventing the spread of disease between communities by changing the structure of the contact network through pharmaceutical or non-pharmaceutical interventions. We use empirical and simulated networks to investigate the spread of disease in networks with community structure. We find that community structure has a major impact on disease dynamics, and we show that in networks with strong community structure, immunization interventions targeted at individuals bridging communities are more effective than those simply targeting highly connected individuals. Because the structure of relevant contact networks is generally not known, and vaccine supply is often limited, there is great need for efficient vaccination algorithms that do not require full knowledge of the network. We developed an algorithm that acts only on locally available network information and is able to quickly identify targets for successful immunization intervention. The algorithm generally outperforms existing algorithms when vaccine supply is limited, particularly in networks with strong community structure. Understanding the spread of infectious diseases and designing optimal control strategies is a major goal of public health. Social networks show marked patterns of community structure, and our results, based on empirical and simulated data, demonstrate that community structure strongly affects disease dynamics. These results have implications for the design of control strategies.",2010 Apr 8,"['Salathé, Marcel', 'Jones, James H.']",PLoS Comput Biol,,,True
68ac410cd36c5699f58d2b76b0eeb84956573f77,PMC,"SARS-CoV Pathogenesis Is Regulated by a STAT1 Dependent but a Type I, II and III Interferon Receptor Independent Mechanism",http://dx.doi.org/10.1371/journal.ppat.1000849,PMC2851658,20386712,CC0,"Severe acute respiratory syndrome coronavirus (SARS-CoV) infection often caused severe end stage lung disease and organizing phase diffuse alveolar damage, especially in the elderly. The virus-host interactions that governed development of these acute end stage lung diseases and death are unknown. To address this question, we evaluated the role of innate immune signaling in protection from human (Urbani) and a recombinant mouse adapted SARS-CoV, designated rMA15. In contrast to most models of viral pathogenesis, infection of type I, type II or type III interferon knockout mice (129 background) with either Urbani or MA15 viruses resulted in clinical disease outcomes, including transient weight loss, denuding bronchiolitis and alveolar inflammation and recovery, identical to that seen in infection of wildtype mice. This suggests that type I, II and III interferon signaling play minor roles in regulating SARS pathogenesis in mouse models. In contrast, infection of STAT1−/− mice resulted in severe disease, high virus titer, extensive pulmonary lesions and 100% mortality by day 9 and 30 post-infection with rMA15 or Urbani viruses, respectively. Non-lethal in BALB/c mice, Urbani SARS-CoV infection in STAT1−/− mice caused disseminated infection involving the liver, spleen and other tissues after day 9. These findings demonstrated that SARS-CoV pathogenesis is regulated by a STAT1 dependent but type I, II and III interferon receptor independent, mechanism. In contrast to a well documented role in innate immunity, we propose that STAT1 also protects mice via its role as an antagonist of unrestrained cell proliferation.",2010 Apr 8,"['Frieman, Matthew B.', 'Chen, Jun', 'Morrison, Thomas E.', 'Whitmore, Alan', 'Funkhouser, William', 'Ward, Jerrold M.', 'Lamirande, Elaine W.', 'Roberts, Anjeanette', 'Heise, Mark', 'Subbarao, Kanta', 'Baric, Ralph S.']",PLoS Pathog,,,True
8d882efc1f6cf141ce6b4283acd7f87b1b280313,PMC,Computer-assisted resilience training to prepare healthcare workers for pandemic influenza: a randomized trial of the optimal dose of training,http://dx.doi.org/10.1186/1472-6963-10-72,PMC2851711,20307302,CC BY,"BACKGROUND: Working in a hospital during an extraordinary infectious disease outbreak can cause significant stress and contribute to healthcare workers choosing to reduce patient contact. Psychological training of healthcare workers prior to an influenza pandemic may reduce stress-related absenteeism, however, established training methods that change behavior and attitudes are too resource-intensive for widespread use. This study tests the feasibility and effectiveness of a less expensive alternative - an interactive, computer-assisted training course designed to build resilience to the stresses of working during a pandemic. METHODS: A ""dose-finding"" study compared pre-post changes in three different durations of training. We measured variables that are likely to mediate stress-responses in a pandemic before and after training: confidence in support and training, pandemic-related self-efficacy, coping style and interpersonal problems. RESULTS: 158 hospital workers took the course and were randomly assigned to the short (7 sessions, median cumulative duration 111 minutes), medium (12 sessions, 158 minutes) or long (17 sessions, 223 minutes) version. Using an intention-to-treat analysis, the course was associated with significant improvements in confidence in support and training, pandemic self-efficacy and interpersonal problems. Participants who under-utilized coping via problem-solving or seeking support or over-utilized escape-avoidance experienced improved coping. Comparison of doses showed improved interpersonal problems in the medium and long course but not in the short course. There was a trend towards higher drop-out rates with longer duration of training. CONCLUSIONS: Computer-assisted resilience training in healthcare workers appears to be of significant benefit and merits further study under pandemic conditions. Comparing three ""doses"" of the course suggested that the medium course was optimal.",2010 Mar 22,"['Maunder, Robert G', 'Lancee, William J', 'Mae, Reet', 'Vincent, Leslie', 'Peladeau, Nathalie', 'Beduz, Mary Agnes', 'Hunter, Jonathan J', 'Leszcz, Molyn']",BMC Health Serv Res,,,True
6204b15a79e3551e09c29cd4865fae0497462ec3,PMC,Generation of Human CEACAM1 Transgenic Mice and Binding of Neisseria Opa Protein to Their Neutrophils,http://dx.doi.org/10.1371/journal.pone.0010067,PMC2852402,20404914,CC BY,"BACKGROUND: Human CEACAM1 is a cell-cell adhesion molecule with multiple functions including insulin clearance in the liver, vasculogenesis in endothelial cells, lumen formation in the mammary gland, and binding of certain human pathogens. PRINCIPAL FINDINGS: Three genomic BAC clones containing the human CEACAM1 gene were microinjected into pronuclei of fertilized FVB mouse oocytes. The embryos were implanted in the oviducts of pseudopregnant females and allowed to develop to term. DNA from newborn mice was evaluated by PCR for the presence of the human CEACAM1 gene. Feces of the PCR positive offspring screened for expression of human CEACAM1. Using this assay, one out of five PCR positive lines was positive for human CEACAM1 expression and showed stable transmission to the F1 generation with the expected transmission frequency (0.5) for heterozygotes. Liver, lung, intestine, kidney, mammary gland, and prostate were strongly positive for the dual expression of both murine and human CEACAM1 and mimic that seen in human tissue. Peripheral blood and bone marrow granulocytes stained strongly for human CEACAM1 and bound Neisseria Opa proteins similar to that in human neutrophils. CONCLUSION: These transgenic animals may serve as a model for the binding of human pathogens to human CEACAM1.",2010 Apr 9,"['Gu, Angel', 'Zhang, Zhifang', 'Zhang, Nan', 'Tsark, Walter', 'Shively, John E.']",PLoS One,,,True
60cd26dae93a4048b5aceb66c68bec325392fdf0,PMC,BioTorrents: A File Sharing Service for Scientific Data,http://dx.doi.org/10.1371/journal.pone.0010071,PMC2854681,20418944,CC BY,"The transfer of scientific data has emerged as a significant challenge, as datasets continue to grow in size and demand for open access sharing increases. Current methods for file transfer do not scale well for large files and can cause long transfer times. In this study we present BioTorrents, a website that allows open access sharing of scientific data and uses the popular BitTorrent peer-to-peer file sharing technology. BioTorrents allows files to be transferred rapidly due to the sharing of bandwidth across multiple institutions and provides more reliable file transfers due to the built-in error checking of the file sharing technology. BioTorrents contains multiple features, including keyword searching, category browsing, RSS feeds, torrent comments, and a discussion forum. BioTorrents is available at http://www.biotorrents.net.",2010 Apr 14,"['Langille, Morgan G. I.', 'Eisen, Jonathan A.']",PLoS One,,,True
5484795b90c22596ead5f0b9ccf08d95a3e6f5c2,PMC,In Vitro Reconstitution of SARS-Coronavirus mRNA Cap Methylation,http://dx.doi.org/10.1371/journal.ppat.1000863,PMC2858705,20421945,CC BY,"SARS-coronavirus (SARS-CoV) genome expression depends on the synthesis of a set of mRNAs, which presumably are capped at their 5′ end and direct the synthesis of all viral proteins in the infected cell. Sixteen viral non-structural proteins (nsp1 to nsp16) constitute an unusually large replicase complex, which includes two methyltransferases putatively involved in viral mRNA cap formation. The S-adenosyl-L-methionine (AdoMet)-dependent (guanine-N7)-methyltransferase (N7-MTase) activity was recently attributed to nsp14, whereas nsp16 has been predicted to be the AdoMet-dependent (nucleoside-2′O)-methyltransferase. Here, we have reconstituted complete SARS-CoV mRNA cap methylation in vitro. We show that mRNA cap methylation requires a third viral protein, nsp10, which acts as an essential trigger to complete RNA cap-1 formation. The obligate sequence of methylation events is initiated by nsp14, which first methylates capped RNA transcripts to generate cap-0 (7Me)GpppA-RNAs. The latter are then selectively 2′O-methylated by the 2′O-MTase nsp16 in complex with its activator nsp10 to give rise to cap-1 (7Me)GpppA(2′OMe)-RNAs. Furthermore, sensitive in vitro inhibition assays of both activities show that aurintricarboxylic acid, active in SARS-CoV infected cells, targets both MTases with IC(50) values in the micromolar range, providing a validated basis for anti-coronavirus drug design.",2010 Apr 22,"['Bouvet, Mickaël', 'Debarnot, Claire', 'Imbert, Isabelle', 'Selisko, Barbara', 'Snijder, Eric J.', 'Canard, Bruno', 'Decroly, Etienne']",PLoS Pathog,,,True
5ca920dabf09c2c2dd2c62f8ef5917e3bd72f087,PMC,The Effect of Vaccination on the Evolution and Population Dynamics of Avian Paramyxovirus-1,http://dx.doi.org/10.1371/journal.ppat.1000872,PMC2858710,20421950,CC BY,"Newcastle Disease Virus (NDV) is a pathogenic strain of avian paramyxovirus (aPMV-1) that is among the most serious of disease threats to the poultry industry worldwide. Viral diversity is high in aPMV-1; eight genotypes are recognized based on phylogenetic reconstruction of gene sequences. Modified live vaccines have been developed to decrease the economic losses caused by this virus. Vaccines derived from avirulent genotype II strains were developed in the 1950s and are in use globally, whereas Australian strains belonging to genotype I were developed as vaccines in the 1970s and are used mainly in Asia. In this study, we evaluated the consequences of attenuated live virus vaccination on the evolution of aPMV-1 genotypes. There was phylogenetic incongruence among trees based on individual genes and complete coding region of 54 full length aPMV-1 genomes, suggesting that recombinant sequences were present in the data set. Subsequently, five recombinant genomes were identified, four of which contained sequences from either genotype I or II. The population history of vaccine-related genotype II strains was distinct from other aPMV-1 genotypes; genotype II emerged in the late 19(th) century and is evolving more slowly than other genotypes, which emerged in the 1960s. Despite vaccination efforts, genotype II viruses have experienced constant population growth to the present. In contrast, other contemporary genotypes showed population declines in the late 1990s. Additionally, genotype I and II viruses, which are circulating in the presence of homotypic vaccine pressure, have unique selection profiles compared to nonvaccine-related strains. Collectively, these data show that vaccination with live attenuated viruses has changed the evolution of aPMV-1 by maintaining a large effective population size of a vaccine-related genotype, allowing for coinfection and recombination of vaccine and wild type strains, and by applying unique selective pressures on viral glycoproteins.",2010 Apr 22,"['Chong, Yee Ling', 'Padhi, Abinash', 'Hudson, Peter J.', 'Poss, Mary']",PLoS Pathog,,,True
f7c3160bef4169d29e2a8bdd79dd6e9056d4774c,PMC,Chikungunya: A Potentially Emerging Epidemic?,http://dx.doi.org/10.1371/journal.pntd.0000623,PMC2860491,20436958,CC BY,"Chikungunya virus is a mosquito-borne emerging pathogen that has a major health impact in humans and causes fever disease, headache, rash, nausea, vomiting, myalgia, and arthralgia. Indigenous to tropical Africa, recent large outbreaks have been reported in parts of South East Asia and several of its neighboring islands in 2005–07 and in Europe in 2007. Furthermore, positive cases have been confirmed in the United States in travelers returning from known outbreak areas. Currently, there is no vaccine or antiviral treatment. With the threat of an emerging global pandemic, the peculiar problems associated with the more immediate and seasonal epidemics warrant the development of an effective vaccine. In this review, we summarize the evidence supporting these concepts.",2010 Apr 27,"['Thiboutot, Michelle M.', 'Kannan, Senthil', 'Kawalekar, Omkar U.', 'Shedlock, Devon J.', 'Khan, Amir S.', 'Sarangan, Gopalsamy', 'Srikanth, Padma', 'Weiner, David B.', 'Muthumani, Karuppiah']",PLoS Negl Trop Dis,,,True
d69356747d4f5a940f9d2ee6e643d895b33f678e,PMC,China's Engagement with Global Health Diplomacy: Was SARS a Watershed?,http://dx.doi.org/10.1371/journal.pmed.1000266,PMC2860492,20436959,CC BY,"As part of the PLoS Medicine series on Global Health Diplomacy, Lai-Han Chan and colleagues provide a case study of China's growing engagement in global health diplomacy following the SARS epidemic.",2010 Apr 27,"['Chan, Lai-Ha', 'Chen, Lucy', 'Xu, Jin']",PLoS Med,,,True
f407fa076e02563e41223d43873e7fd604bdd637,PMC,Chloroquine and Its Derivatives Exacerbate B19V-Associated Anemia by Promoting Viral Replication,http://dx.doi.org/10.1371/journal.pntd.0000669,PMC2860510,20436917,CC BY,"BACKGROUND: An unexpectedly high seroprevalence and pathogenic potential of human parvovirus B19 (B19V) have been observed in certain malaria-endemic countries in parallel with local use of chloroquine (CQ) as first-line treatment for malaria. The aims of this study were to assess the effect of CQ and other common antimalarial drugs on B19V infection in vitro and the possible epidemiological consequences for children from Papua New Guinea (PNG). METHODOLOGY/PRINCIPAL FINDINGS: Viral RNA, DNA and proteins were analyzed in different cell types following infection with B19V in the presence of a range of antimalarial drugs. Relationships between B19V infection status, prior 4-aminoquinoline use and anemia were assessed in 200 PNG children <10 years of age participating in a case-control study of severe infections. In CQ-treated cells, the synthesis of viral RNA, DNA and proteins was significantly higher and occurred earlier than in control cells. CQ facilitates B19V infection by minimizing intracellular degradation of incoming particles. Only amodiaquine amongst other antimalarial drugs had a similar effect. B19V IgM seropositivity was more frequent in 111 children with severe anemia (hemoglobin <50 g/L) than in 89 healthy controls (15.3% vs 3.4%; P = 0.008). In children who were either B19V IgM or PCR positive, 4-aminoquinoline use was associated with a significantly lower admission hemoglobin concentration. CONCLUSIONS/SIGNIFICANCE: Our data strongly suggest that 4-aminoquinoline drugs and their metabolites exacerbate B19V-associated anemia by promoting B19V replication. Consideration should be given for choosing a non-4-aminoquinoline drug to partner artemisinin compounds in combination antimalarial therapy.",2010 Apr 27,"['Bönsch, Claudia', 'Kempf, Christoph', 'Mueller, Ivo', 'Manning, Laurens', 'Laman, Moses', 'Davis, Timothy M. E.', 'Ros, Carlos']",PLoS Negl Trop Dis,,,True
c0f7f46699d0ecf0c7ead699d564d952508e6f81,PMC,Behavioural intentions in response to an influenza pandemic,http://dx.doi.org/10.1186/1471-2458-10-174,PMC2861057,20353568,CC BY,"BACKGROUND: Little is known regarding which behavioural responses can be expected if an influenza pandemic were to occur. METHODS: A survey comprising questions based on risk perception theories, in particular PMT, was conducted with a Dutch sample. RESULTS: Although fear that an influenza pandemic may occur was high, participants do not feel well informed. General practitioners and local health authorities were considered trustworthy sources of information and the information considered most urgent pertained to which protective measures should be taken. Participants reported an intention to comply with recommendations regarding protective measures. However, response and self efficacy were low. Maladaptive behaviours can be expected. Increasing numbers of ill individuals and school closures are also expected to lead to a decreased work force. Participants indicated wanting antiviral drugs even if the supply were to be insufficient. CONCLUSIONS: Messages regarding health protective behaviours from local health authorities should anticipate the balance between overreacting and underreacting. Also, when protective recommendations from health professionals conflict with company policies, it is unclear how employees will react.",2010 Mar 30,"['Kok, Gerjo', 'Jonkers, Ruud', 'Gelissen, Roger', 'Meertens, Ree', 'Schaalma, Herman', 'de Zwart, Onno']",BMC Public Health,,,True
6fb63e6ddb93b95e451c44a18ca67e506e126c3d,PMC,Syndromic Surveillance for Local Outbreaks of Lower-Respiratory Infections: Would It Work?,http://dx.doi.org/10.1371/journal.pone.0010406,PMC2861591,20454449,CC BY,"BACKGROUND: Although syndromic surveillance is increasingly used to detect unusual illness, there is a debate whether it is useful for detecting local outbreaks. We evaluated whether syndromic surveillance detects local outbreaks of lower-respiratory infections (LRIs) without swamping true signals by false alarms. METHODS AND FINDINGS: Using retrospective hospitalization data, we simulated prospective surveillance for LRI-elevations. Between 1999–2006, a total of 290762 LRIs were included by date of hospitalization and patients place of residence (>80% coverage, 16 million population). Two large outbreaks of Legionnaires disease in the Netherlands were used as positive controls to test whether these outbreaks could have been detected as local LRI elevations. We used a space-time permutation scan statistic to detect LRI clusters. We evaluated how many LRI-clusters were detected in 1999–2006 and assessed likely causes for the cluster-signals by looking for significantly higher proportions of specific hospital discharge diagnoses (e.g. Legionnaires disease) and overlap with regional influenza elevations. We also evaluated whether the number of space-time signals can be reduced by restricting the scan statistic in space or time. In 1999–2006 the scan-statistic detected 35 local LRI clusters, representing on average 5 clusters per year. The known Legionnaires' disease outbreaks in 1999 and 2006 were detected as LRI-clusters, since cluster-signals were generated with an increased proportion of Legionnaires disease patients (p:<0.0001). 21 other clusters coincided with local influenza and/or respiratory syncytial virus activity, and 1 cluster appeared to be a data artifact. For 11 clusters no likely cause was defined, some possibly representing as yet undetected LRI-outbreaks. With restrictions on time and spatial windows the scan statistic still detected the Legionnaires' disease outbreaks, without loss of timeliness and with less signals generated in time (up to 42% decline). CONCLUSIONS: To our knowledge this is the first study that systematically evaluates the performance of space-time syndromic surveillance with nationwide high coverage data over a longer period. The results show that syndromic surveillance can detect local LRI-outbreaks in a timely manner, independent of laboratory-based outbreak detection. Furthermore, since comparatively few new clusters per year were observed that would prompt investigation, syndromic hospital-surveillance could be a valuable tool for detection of local LRI-outbreaks.",2010 Apr 29,"['van den Wijngaard, Cees C.', 'van Asten, Liselotte', 'van Pelt, Wilfrid', 'Doornbos, Gerda', 'Nagelkerke, Nico J. D.', 'Donker, Gé A.', 'van der Hoek, Wim', 'Koopmans, Marion P. G.']",PLoS One,,,True
44ab6aecdacb870226ce4ce36606e227f0a6ac00,PMC,Electron Tomography Reveals the Steps in Filovirus Budding,http://dx.doi.org/10.1371/journal.ppat.1000875,PMC2861712,20442788,CC BY,"The filoviruses, Marburg and Ebola, are non-segmented negative-strand RNA viruses causing severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. The sequence of events that leads to release of filovirus particles from cells is poorly understood. Two contrasting mechanisms have been proposed, one proceeding via a “submarine-like” budding with the helical nucleocapsid emerging parallel to the plasma membrane, and the other via perpendicular “rocket-like” protrusion. Here we have infected cells with Marburg virus under BSL-4 containment conditions, and reconstructed the sequence of steps in the budding process in three dimensions using electron tomography of plastic-embedded cells. We find that highly infectious filamentous particles are released at early stages in infection. Budding proceeds via lateral association of intracellular nucleocapsid along its whole length with the plasma membrane, followed by rapid envelopment initiated at one end of the nucleocapsid, leading to a protruding intermediate. Scission results in local membrane instability at the rear of the virus. After prolonged infection, increased vesiculation of the plasma membrane correlates with changes in shape and infectivity of released viruses. Our observations demonstrate a cellular determinant of virus shape. They reconcile the contrasting models of filovirus budding and allow us to describe the sequence of events taking place during budding and release of Marburg virus. We propose that this represents a general sequence of events also followed by other filamentous and rod-shaped viruses.",2010 Apr 29,"['Welsch, Sonja', 'Kolesnikova, Larissa', 'Krähling, Verena', 'Riches, James D.', 'Becker, Stephan', 'Briggs, John A. G.']",PLoS Pathog,,,True
58a9c23ad5702fdc007f682342e3a77fe5516a8f,PMC,HAb18G/CD147 cell-cell contacts confer resistance of a HEK293 subpopulation to anoikis in an E-cadherin-dependent manner,http://dx.doi.org/10.1186/1471-2121-11-27,PMC2864199,20398401,CC BY,"BACKGROUND: Acquisition of resistance to ""anoikis"" facilitates the survival of cells under independent matrix-deficient conditions, such as cells in tumor progression and the production of suspension culture cells for biomedical engineering. There is evidence suggesting that CD147, an adhesion molecule associated with survival of cells in tumor metastasis and cell-cell contacts, plays an important role in resistance to anoikis. However, information regarding the functions of CD147 in mediating cell-cell contacts and anoikis-resistance remains limited and even self-contradictory. RESULTS: An anoikis-resistant clone (HEK293ar), derived from anoikis-sensitive parental Human Embryonic Kidney 293 cells, survived anoikis by the formation of cell-cell contacts. The expression of HAb18G/CD147 (a member of the CD147 family) was upregulated and the protein was located at cell-cell junctions. Upregulation of HAb18G/CD147 in suspended HEK293ar cells suppressed anoikis by mediating the formation of cell-cell adhesions. Anoikis resistance in HEK293ar cells also required E-cadherin-mediated cell-cell contacts. Knock-down of HAb18G/CD147 and E-cadherin inhibited cell-cell contacts formation and increased anoikis sensitivity respectively. When HAb18G/CD147 was downregulated, E-cadherin expression in HEK293ar cells was significantly suppressed; however, knockdown of E-cadherin by E-cadherin siRNA or blocking of E-cadherin binding activity with a specific antibody and EDTA had no significant effect on HAb18G/CD147 expression. Finally, pretreatment with LY294002, a phosphoinositide 3-kinase (PI3K/AKT) inhibitor, disrupted cell-cell contacts and decreased cell number, but this was not the case in cells treated with the extracellular signal-regulated kinase (ERK) inhibitor PD98059. CONCLUSIONS: Our results provide new evidence that HAb18G/CD147-mediated cell-cell contact confers anoikis resistance in an E-cadherin-dependent manner; and cell-cell contact mediated resistance to anoikis implicates PI3K pathway in a highly relevant cell model (HEK293ar). Understanding of the role of HAb18G/CD147 cell-cell contacts in anoikis resistance may help in understanding the survival of cells in anchorage-independent growth, such as cells in tumor metastasis and suspension culture produced for biomedical engineering. Our results also contribute to a better understanding of the biology of HEK293 cell spheroids, a major workhorse for producing human therapeutic agents and viral vaccines.",2010 Apr 17,"['Ma, Xiao-Kui', 'Wang, Li', 'Li, Yu', 'Yang, Xiang-Ming', 'Zhao, Pu', 'HaoTang', 'Zhu, Ping', 'Li, Ling', 'Chen, Zhi-Nan']",BMC Cell Biol,,,True
8e67618920b0226e661e20a2c36b4436857d9590,PMC,Why do I need it? I am not at risk! Public perceptions towards the pandemic (H1N1) 2009 vaccine,http://dx.doi.org/10.1186/1471-2334-10-99,PMC2864274,20403201,CC BY,"BACKGROUND: On the 30th September 2009, the pandemic (H1N1) 2009 influenza vaccine was made available to adults and children aged 10 years and over, in Australia. Acceptance of a novel vaccine is influenced by perceptions of risk including risk of infection, risk of death or severe illness and risk of serious vaccine side-effects. We surveyed a sample of residents from Sydney, Australia to ascertain their risk perception, attitudes towards the pandemic and willingness to accept the pandemic (H1N1) 2009 influenza vaccine. METHODS: We sampled residents using a cross-sectional intercept design during the WHO Phase 6. Members of the public were approached in shopping and pedestrian malls to undertake the survey during September and October 2009. The survey measured perceived risk, seriousness of disease, recent behavioural changes, likely acceptance of the pandemic (H1N1) 2009 vaccine and issues relating to uptake and perceived safety. RESULTS: Of the 627 respondents, the majority felt that they had a ""very low to low"" (332/627, 52.9%) risk of acquiring H1N1. 24.5% (154/627) of respondents believed that the disease would ""very seriously or extremely"" affect their health. Nearly half (305/627, 48.6%) reported that in response to the ""swine flu"" outbreak they had undertaken one or more of the investigated behavioural changes. Overall, the self-reported likelihood of accepting vaccination against novel H1N1 was 54.7% (343/627). CONCLUSIONS: While, most participants did not believe they were at high risk of acquiring pandemic H1N1 2009, over half of the sample indicated that they would accept the vaccine. Participants who were vaccinated against the seasonal influenza were more likely to receive the H1N1 vaccine. Concerns about safety, the possibility of side effects and the vaccine development process need to be addressed.",2010 Apr 19,"['Seale, Holly', 'Heywood, Anita E', 'McLaws, Mary-Louise', 'Ward, Kirsten F', 'Lowbridge, Chris P', 'Van, Debbie', 'MacIntyre, C Raina']",BMC Infect Dis,,,True
859e22ac7ded4f546d8f58cc6d8515bd261b5289,PMC,Anatomy of the Epidemiological Literature on the 2003 SARS Outbreaks in Hong Kong and Toronto: A Time-Stratified Review,http://dx.doi.org/10.1371/journal.pmed.1000272,PMC2864302,20454570,CC BY,"BACKGROUND: Outbreaks of emerging infectious diseases, especially those of a global nature, require rapid epidemiological analysis and information dissemination. The final products of those activities usually comprise internal memoranda and briefs within public health authorities and original research published in peer-reviewed journals. Using the 2003 severe acute respiratory syndrome (SARS) epidemic as an example, we conducted a comprehensive time-stratified review of the published literature to describe the different types of epidemiological outputs. METHODS AND FINDINGS: We identified and analyzed all published articles on the epidemiology of the SARS outbreak in Hong Kong or Toronto. The analysis was stratified by study design, research domain, data collection, and analytical technique. We compared the SARS-case and matched-control non-SARS articles published according to the timeline of submission, acceptance, and publication. The impact factors of the publishing journals were examined according to the time of publication of SARS articles, and the numbers of citations received by SARS-case and matched-control articles submitted during and after the epidemic were compared. Descriptive, analytical, theoretical, and experimental epidemiology concerned, respectively, 54%, 30%, 11%, and 6% of the studies. Only 22% of the studies were submitted, 8% accepted, and 7% published during the epidemic. The submission-to-acceptance and acceptance-to-publication intervals of the SARS articles submitted during the epidemic period were significantly shorter than the corresponding intervals of matched-control non-SARS articles published in the same journal issues (p<0.001 and p<0.01, respectively). The differences of median submission-to-acceptance intervals and median acceptance-to-publication intervals between SARS articles and their corresponding control articles were 106.5 d (95% confidence interval [CI] 55.0–140.1) and 63.5 d (95% CI 18.0–94.1), respectively. The median numbers of citations of the SARS articles submitted during the epidemic and over the 2 y thereafter were 17 (interquartile range [IQR] 8.0–52.0) and 8 (IQR 3.2–21.8), respectively, significantly higher than the median numbers of control article citations (15, IQR 8.5–16.5, p<0.05, and 7, IQR 3.0–12.0, p<0.01, respectively). CONCLUSIONS: A majority of the epidemiological articles on SARS were submitted after the epidemic had ended, although the corresponding studies had relevance to public health authorities during the epidemic. To minimize the lag between research and the exigency of public health practice in the future, researchers should consider adopting common, predefined protocols and ready-to-use instruments to improve timeliness, and thus, relevance, in addition to standardizing comparability across studies. To facilitate information dissemination, journal managers should reengineer their fast-track channels, which should be adapted to the purpose of an emerging outbreak, taking into account the requirement of high standards of quality for scientific journals and competition with other online resources. Please see later in the article for the Editors' Summary",2010 May 4,"['Xing, Weijia', 'Hejblum, Gilles', 'Leung, Gabriel M.', 'Valleron, Alain-Jacques']",PLoS Med,,,True
5ac30e981ededacfc6671f36634a88e6ce139e39,PMC,Anatomy of the Epidemiological Literature on the 2003 SARS Outbreaks in Hong Kong and Toronto: A Time-Stratified Review,http://dx.doi.org/10.1371/journal.pmed.1000272,PMC2864302,20454570,CC BY,"BACKGROUND: Outbreaks of emerging infectious diseases, especially those of a global nature, require rapid epidemiological analysis and information dissemination. The final products of those activities usually comprise internal memoranda and briefs within public health authorities and original research published in peer-reviewed journals. Using the 2003 severe acute respiratory syndrome (SARS) epidemic as an example, we conducted a comprehensive time-stratified review of the published literature to describe the different types of epidemiological outputs. METHODS AND FINDINGS: We identified and analyzed all published articles on the epidemiology of the SARS outbreak in Hong Kong or Toronto. The analysis was stratified by study design, research domain, data collection, and analytical technique. We compared the SARS-case and matched-control non-SARS articles published according to the timeline of submission, acceptance, and publication. The impact factors of the publishing journals were examined according to the time of publication of SARS articles, and the numbers of citations received by SARS-case and matched-control articles submitted during and after the epidemic were compared. Descriptive, analytical, theoretical, and experimental epidemiology concerned, respectively, 54%, 30%, 11%, and 6% of the studies. Only 22% of the studies were submitted, 8% accepted, and 7% published during the epidemic. The submission-to-acceptance and acceptance-to-publication intervals of the SARS articles submitted during the epidemic period were significantly shorter than the corresponding intervals of matched-control non-SARS articles published in the same journal issues (p<0.001 and p<0.01, respectively). The differences of median submission-to-acceptance intervals and median acceptance-to-publication intervals between SARS articles and their corresponding control articles were 106.5 d (95% confidence interval [CI] 55.0–140.1) and 63.5 d (95% CI 18.0–94.1), respectively. The median numbers of citations of the SARS articles submitted during the epidemic and over the 2 y thereafter were 17 (interquartile range [IQR] 8.0–52.0) and 8 (IQR 3.2–21.8), respectively, significantly higher than the median numbers of control article citations (15, IQR 8.5–16.5, p<0.05, and 7, IQR 3.0–12.0, p<0.01, respectively). CONCLUSIONS: A majority of the epidemiological articles on SARS were submitted after the epidemic had ended, although the corresponding studies had relevance to public health authorities during the epidemic. To minimize the lag between research and the exigency of public health practice in the future, researchers should consider adopting common, predefined protocols and ready-to-use instruments to improve timeliness, and thus, relevance, in addition to standardizing comparability across studies. To facilitate information dissemination, journal managers should reengineer their fast-track channels, which should be adapted to the purpose of an emerging outbreak, taking into account the requirement of high standards of quality for scientific journals and competition with other online resources. Please see later in the article for the Editors' Summary",2010 May 4,"['Xing, Weijia', 'Hejblum, Gilles', 'Leung, Gabriel M.', 'Valleron, Alain-Jacques']",PLoS Med,,,False
936d646d345dd1d9e2df55574f53ebae22c29146,PMC,Anatomy of the Epidemiological Literature on the 2003 SARS Outbreaks in Hong Kong and Toronto: A Time-Stratified Review,http://dx.doi.org/10.1371/journal.pmed.1000272,PMC2864302,20454570,CC BY,"BACKGROUND: Outbreaks of emerging infectious diseases, especially those of a global nature, require rapid epidemiological analysis and information dissemination. The final products of those activities usually comprise internal memoranda and briefs within public health authorities and original research published in peer-reviewed journals. Using the 2003 severe acute respiratory syndrome (SARS) epidemic as an example, we conducted a comprehensive time-stratified review of the published literature to describe the different types of epidemiological outputs. METHODS AND FINDINGS: We identified and analyzed all published articles on the epidemiology of the SARS outbreak in Hong Kong or Toronto. The analysis was stratified by study design, research domain, data collection, and analytical technique. We compared the SARS-case and matched-control non-SARS articles published according to the timeline of submission, acceptance, and publication. The impact factors of the publishing journals were examined according to the time of publication of SARS articles, and the numbers of citations received by SARS-case and matched-control articles submitted during and after the epidemic were compared. Descriptive, analytical, theoretical, and experimental epidemiology concerned, respectively, 54%, 30%, 11%, and 6% of the studies. Only 22% of the studies were submitted, 8% accepted, and 7% published during the epidemic. The submission-to-acceptance and acceptance-to-publication intervals of the SARS articles submitted during the epidemic period were significantly shorter than the corresponding intervals of matched-control non-SARS articles published in the same journal issues (p<0.001 and p<0.01, respectively). The differences of median submission-to-acceptance intervals and median acceptance-to-publication intervals between SARS articles and their corresponding control articles were 106.5 d (95% confidence interval [CI] 55.0–140.1) and 63.5 d (95% CI 18.0–94.1), respectively. The median numbers of citations of the SARS articles submitted during the epidemic and over the 2 y thereafter were 17 (interquartile range [IQR] 8.0–52.0) and 8 (IQR 3.2–21.8), respectively, significantly higher than the median numbers of control article citations (15, IQR 8.5–16.5, p<0.05, and 7, IQR 3.0–12.0, p<0.01, respectively). CONCLUSIONS: A majority of the epidemiological articles on SARS were submitted after the epidemic had ended, although the corresponding studies had relevance to public health authorities during the epidemic. To minimize the lag between research and the exigency of public health practice in the future, researchers should consider adopting common, predefined protocols and ready-to-use instruments to improve timeliness, and thus, relevance, in addition to standardizing comparability across studies. To facilitate information dissemination, journal managers should reengineer their fast-track channels, which should be adapted to the purpose of an emerging outbreak, taking into account the requirement of high standards of quality for scientific journals and competition with other online resources. Please see later in the article for the Editors' Summary",2010 May 4,"['Xing, Weijia', 'Hejblum, Gilles', 'Leung, Gabriel M.', 'Valleron, Alain-Jacques']",PLoS Med,,,True
a4ee99345c99a1f9806c8d17dc7e6accaf5309d6,PMC,Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy,http://dx.doi.org/10.1155/2010/723798,PMC2864512,20454584,CC BY,"Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.",2010 May 5,"['Wu, Han-Chung', 'Chang, De-Kuan']",J Oncol,,,True
c9b0389a55de2f9cbfe37049d1072e0984613923,PMC,Elevation of Intact and Proteolytic Fragments of Acute Phase Proteins Constitutes the Earliest Systemic Antiviral Response in HIV-1 Infection,http://dx.doi.org/10.1371/journal.ppat.1000893,PMC2865525,20463814,CC BY,"The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI) exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages and DCs, NK cells, β-defensins, complement and other anti-microbial factors, which have all been implicated in modulating HIV infection, may play particularly important roles. A proteomics-based screen was performed on a cohort from whom samples were available at time points prior to the earliest positive HIV detection. The ability of selected factors found to be elevated in the plasma during AHI to inhibit HIV-1 replication was analyzed using in vitro PBMC and DC infection models. Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI. Induction of acute phase protein serum amyloid A (A-SAA) occurred as early as 5–7 days prior to the first detection of plasma viral RNA, considerably prior to any elevation in systemic cytokine levels. Furthermore, a proteolytic fragment of alpha–1-antitrypsin (AAT), termed virus inhibitory peptide (VIRIP), was observed in plasma coincident with viremia. Both A-SAA and VIRIP have anti-viral activity in vitro and quantitation of their plasma levels indicated that circulating concentrations are likely to be within the range of their inhibitory activity. Our results provide evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses. Insights gained into the mechanism of action of acute-phase reactants and other innate molecules against HIV and how they are induced could be exploited for the future development of more efficient prophylactic vaccine strategies.",2010 May 6,"['Kramer, Holger B.', 'Lavender, Kerry J.', 'Qin, Li', 'Stacey, Andrea R.', 'Liu, Michael K. P.', 'di Gleria, Katalin', 'Simmons, Alison', 'Gasper-Smith, Nancy', 'Haynes, Barton F.', 'McMichael, Andrew J.', 'Borrow, Persephone', 'Kessler, Benedikt M.']",PLoS Pathog,,,True
f34ff3679970e1119e87bc6df13848be35a217a4,PMC,Elevation of Intact and Proteolytic Fragments of Acute Phase Proteins Constitutes the Earliest Systemic Antiviral Response in HIV-1 Infection,http://dx.doi.org/10.1371/journal.ppat.1000893,PMC2865525,20463814,CC BY,"The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI) exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages and DCs, NK cells, β-defensins, complement and other anti-microbial factors, which have all been implicated in modulating HIV infection, may play particularly important roles. A proteomics-based screen was performed on a cohort from whom samples were available at time points prior to the earliest positive HIV detection. The ability of selected factors found to be elevated in the plasma during AHI to inhibit HIV-1 replication was analyzed using in vitro PBMC and DC infection models. Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI. Induction of acute phase protein serum amyloid A (A-SAA) occurred as early as 5–7 days prior to the first detection of plasma viral RNA, considerably prior to any elevation in systemic cytokine levels. Furthermore, a proteolytic fragment of alpha–1-antitrypsin (AAT), termed virus inhibitory peptide (VIRIP), was observed in plasma coincident with viremia. Both A-SAA and VIRIP have anti-viral activity in vitro and quantitation of their plasma levels indicated that circulating concentrations are likely to be within the range of their inhibitory activity. Our results provide evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses. Insights gained into the mechanism of action of acute-phase reactants and other innate molecules against HIV and how they are induced could be exploited for the future development of more efficient prophylactic vaccine strategies.",2010 May 6,"['Kramer, Holger B.', 'Lavender, Kerry J.', 'Qin, Li', 'Stacey, Andrea R.', 'Liu, Michael K. P.', 'di Gleria, Katalin', 'Simmons, Alison', 'Gasper-Smith, Nancy', 'Haynes, Barton F.', 'McMichael, Andrew J.', 'Borrow, Persephone', 'Kessler, Benedikt M.']",PLoS Pathog,,,False
97c030ade92e5f7583a228b3332b848e1825cb6d,PMC,Elevation of Intact and Proteolytic Fragments of Acute Phase Proteins Constitutes the Earliest Systemic Antiviral Response in HIV-1 Infection,http://dx.doi.org/10.1371/journal.ppat.1000893,PMC2865525,20463814,CC BY,"The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI) exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages and DCs, NK cells, β-defensins, complement and other anti-microbial factors, which have all been implicated in modulating HIV infection, may play particularly important roles. A proteomics-based screen was performed on a cohort from whom samples were available at time points prior to the earliest positive HIV detection. The ability of selected factors found to be elevated in the plasma during AHI to inhibit HIV-1 replication was analyzed using in vitro PBMC and DC infection models. Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI. Induction of acute phase protein serum amyloid A (A-SAA) occurred as early as 5–7 days prior to the first detection of plasma viral RNA, considerably prior to any elevation in systemic cytokine levels. Furthermore, a proteolytic fragment of alpha–1-antitrypsin (AAT), termed virus inhibitory peptide (VIRIP), was observed in plasma coincident with viremia. Both A-SAA and VIRIP have anti-viral activity in vitro and quantitation of their plasma levels indicated that circulating concentrations are likely to be within the range of their inhibitory activity. Our results provide evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses. Insights gained into the mechanism of action of acute-phase reactants and other innate molecules against HIV and how they are induced could be exploited for the future development of more efficient prophylactic vaccine strategies.",2010 May 6,"['Kramer, Holger B.', 'Lavender, Kerry J.', 'Qin, Li', 'Stacey, Andrea R.', 'Liu, Michael K. P.', 'di Gleria, Katalin', 'Simmons, Alison', 'Gasper-Smith, Nancy', 'Haynes, Barton F.', 'McMichael, Andrew J.', 'Borrow, Persephone', 'Kessler, Benedikt M.']",PLoS Pathog,,,False
eaa85bd1e79e97031aa9a666081d4ad550381fef,PMC,Elevation of Intact and Proteolytic Fragments of Acute Phase Proteins Constitutes the Earliest Systemic Antiviral Response in HIV-1 Infection,http://dx.doi.org/10.1371/journal.ppat.1000893,PMC2865525,20463814,CC BY,"The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI) exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages and DCs, NK cells, β-defensins, complement and other anti-microbial factors, which have all been implicated in modulating HIV infection, may play particularly important roles. A proteomics-based screen was performed on a cohort from whom samples were available at time points prior to the earliest positive HIV detection. The ability of selected factors found to be elevated in the plasma during AHI to inhibit HIV-1 replication was analyzed using in vitro PBMC and DC infection models. Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI. Induction of acute phase protein serum amyloid A (A-SAA) occurred as early as 5–7 days prior to the first detection of plasma viral RNA, considerably prior to any elevation in systemic cytokine levels. Furthermore, a proteolytic fragment of alpha–1-antitrypsin (AAT), termed virus inhibitory peptide (VIRIP), was observed in plasma coincident with viremia. Both A-SAA and VIRIP have anti-viral activity in vitro and quantitation of their plasma levels indicated that circulating concentrations are likely to be within the range of their inhibitory activity. Our results provide evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses. Insights gained into the mechanism of action of acute-phase reactants and other innate molecules against HIV and how they are induced could be exploited for the future development of more efficient prophylactic vaccine strategies.",2010 May 6,"['Kramer, Holger B.', 'Lavender, Kerry J.', 'Qin, Li', 'Stacey, Andrea R.', 'Liu, Michael K. P.', 'di Gleria, Katalin', 'Simmons, Alison', 'Gasper-Smith, Nancy', 'Haynes, Barton F.', 'McMichael, Andrew J.', 'Borrow, Persephone', 'Kessler, Benedikt M.']",PLoS Pathog,,,False
e4007988dba3dcfa65314d50324bdff1ba7f55c2,PMC,Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing,http://dx.doi.org/10.1371/journal.ppat.1000896,PMC2865531,20463816,CC BY,"Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.",2010 May 6,"['Eckerle, Lance D.', 'Becker, Michelle M.', 'Halpin, Rebecca A.', 'Li, Kelvin', 'Venter, Eli', 'Lu, Xiaotao', 'Scherbakova, Sana', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Stockwell, Timothy B.', 'Spiro, David J.', 'Denison, Mark R.']",PLoS Pathog,,,True
dd84d0eafb5b8a5eaaa188b96cee26d26cafce9b,PMC,Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing,http://dx.doi.org/10.1371/journal.ppat.1000896,PMC2865531,20463816,CC BY,"Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.",2010 May 6,"['Eckerle, Lance D.', 'Becker, Michelle M.', 'Halpin, Rebecca A.', 'Li, Kelvin', 'Venter, Eli', 'Lu, Xiaotao', 'Scherbakova, Sana', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Stockwell, Timothy B.', 'Spiro, David J.', 'Denison, Mark R.']",PLoS Pathog,,,False
1d48922e36416e5ca9ccc82b36e08c6141e122ae,PMC,Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing,http://dx.doi.org/10.1371/journal.ppat.1000896,PMC2865531,20463816,CC BY,"Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.",2010 May 6,"['Eckerle, Lance D.', 'Becker, Michelle M.', 'Halpin, Rebecca A.', 'Li, Kelvin', 'Venter, Eli', 'Lu, Xiaotao', 'Scherbakova, Sana', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Stockwell, Timothy B.', 'Spiro, David J.', 'Denison, Mark R.']",PLoS Pathog,,,False
242dcea1de6547489b801ddac02df1d76dfed56e,PMC,Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing,http://dx.doi.org/10.1371/journal.ppat.1000896,PMC2865531,20463816,CC BY,"Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.",2010 May 6,"['Eckerle, Lance D.', 'Becker, Michelle M.', 'Halpin, Rebecca A.', 'Li, Kelvin', 'Venter, Eli', 'Lu, Xiaotao', 'Scherbakova, Sana', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Stockwell, Timothy B.', 'Spiro, David J.', 'Denison, Mark R.']",PLoS Pathog,,,False
79c01be9a0994df6f3574664c006f27f64d95c91,PMC,Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing,http://dx.doi.org/10.1371/journal.ppat.1000896,PMC2865531,20463816,CC BY,"Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.",2010 May 6,"['Eckerle, Lance D.', 'Becker, Michelle M.', 'Halpin, Rebecca A.', 'Li, Kelvin', 'Venter, Eli', 'Lu, Xiaotao', 'Scherbakova, Sana', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Stockwell, Timothy B.', 'Spiro, David J.', 'Denison, Mark R.']",PLoS Pathog,,,False
a20dd031ddcc9073931bc7021026cbce2d331441,PMC,Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing,http://dx.doi.org/10.1371/journal.ppat.1000896,PMC2865531,20463816,CC BY,"Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.",2010 May 6,"['Eckerle, Lance D.', 'Becker, Michelle M.', 'Halpin, Rebecca A.', 'Li, Kelvin', 'Venter, Eli', 'Lu, Xiaotao', 'Scherbakova, Sana', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Stockwell, Timothy B.', 'Spiro, David J.', 'Denison, Mark R.']",PLoS Pathog,,,False
972358c8d4c09b7ace5d8869323a225e41d13c59,PMC,Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing,http://dx.doi.org/10.1371/journal.ppat.1000896,PMC2865531,20463816,CC BY,"Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.",2010 May 6,"['Eckerle, Lance D.', 'Becker, Michelle M.', 'Halpin, Rebecca A.', 'Li, Kelvin', 'Venter, Eli', 'Lu, Xiaotao', 'Scherbakova, Sana', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Stockwell, Timothy B.', 'Spiro, David J.', 'Denison, Mark R.']",PLoS Pathog,,,False
9ceb55e16e0547f12dd8f895b3781a05429fd7b2,PMC,Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing,http://dx.doi.org/10.1371/journal.ppat.1000896,PMC2865531,20463816,CC BY,"Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.",2010 May 6,"['Eckerle, Lance D.', 'Becker, Michelle M.', 'Halpin, Rebecca A.', 'Li, Kelvin', 'Venter, Eli', 'Lu, Xiaotao', 'Scherbakova, Sana', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Stockwell, Timothy B.', 'Spiro, David J.', 'Denison, Mark R.']",PLoS Pathog,,,False
241ba286b5b231ad009c7e9a28c85aacbdff49a9,PMC,Combined analysis of cell growth and apoptosis-regulating proteins in HPVs associated anogenital tumors,http://dx.doi.org/10.1186/1471-2407-10-118,PMC2868050,20346172,CC BY,"BACKGROUND: The clinical course of human papillomavirus (HPV) associated with Bowenoid papulosis and condyloma acuminatum of anogenital tumors are still unknown. Here we evaluated molecules that are relevant to cellular proliferation and regulation of apoptosis in HPV associated anogenital tumors. METHODS: We investigated the levels of telomerase activity, and inhibitor of apoptosis proteins (IAPs) family (c-IAP1, c-IAP2, XIAP) and c-Myc mRNA expression levels in 20 specimens of Bowenoid papulosis and 36 specimens of condyloma acuminatum in anogenital areas. Overall, phosphorylated (p-) AKT, p-ribosomal protein S6 (S6) and p-4E-binding protein 1 (4EBP1) expression levels were examined by immunohistochemistry in anogenital tumors both with and without positive telomerase activity. RESULTS: Positive telomerase activity was detected in 41.7% of Bowenoid papulosis and 27.3% of condyloma acuminatum compared to normal skin (p < 0.001). In contrast, the expression levels of Bowenoid papulosis indicated that c-IAP1, c-IAP2 and XIAP mRNA were significantly upregulated compared to those in both condyloma acuminatum samples (p < 0.001, p < 0.001, p = 0.022, respectively) and normal skin (p < 0.001, p = 0.002, p = 0.034, respectively). Overall, 30% of Bowenoid papulosis with high risk HPV strongly promoted IAPs family and c-Myc but condyloma acuminatum did not significantly activate those genes. Immunohistochemically, p-Akt and p-S6 expressions were associated with positive telomerase activity but not with p-4EBP1 expression. CONCLUSION: Combined analysis of the IAPs family, c-Myc mRNA expression, telomerase activity levels and p-Akt/p-S6 expressions may provide clinically relevant molecular markers in HPV associated anogenital tumors.",2010 Mar 27,"['Mitsuishi, Tsuyoshi', 'Iwabu, Yukie', 'Tokunaga, Kenzo', 'Sata, Tetsutaro', 'Kaneko, Takehiko', 'Ohara, Kuniaki', 'Ohsawa, Ikuroh', 'Oda, Fumino', 'Yamada, Yuko', 'Kawana, Seiji', 'Ozaki, Kohji', 'Nakatake, Mayuka', 'Yamada, Osamu']",BMC Cancer,,,True
ae3594fcd839554d0a4ea161dc9bbd3d1f6dbaa9,PMC,Proper Distance Metrics for Phylogenetic Analysis Using Complete Genomes without Sequence Alignment,http://dx.doi.org/10.3390/ijms11031141,PMC2869232,20480005,CC BY,A shortcoming of most correlation distance methods based on the composition vectors without alignment developed for phylogenetic analysis using complete genomes is that the “distances” are not proper distance metrics in the strict mathematical sense. In this paper we propose two new correlation-related distance metrics to replace the old one in our dynamical language approach. Four genome datasets are employed to evaluate the effects of this replacement from a biological point of view. We find that the two proper distance metrics yield trees with the same or similar topologies as/to those using the old “distance” and agree with the tree of life based on 16S rRNA in a majority of the basic branches. Hence the two proper correlation-related distance metrics proposed here improve our dynamical language approach for phylogenetic analysis.,2010 Mar 18,"['Yu, Zu-Guo', 'Zhan, Xiao-Wen', 'Han, Guo-Sheng', 'Wang, Roger W.', 'Anh, Vo', 'Chu, Ka Hou']",Int J Mol Sci,,,True
2181d2f31f1f4b8c6203668dee4f6b3f382af799,PMC,QSAR Studies on Andrographolide Derivatives as α-Glucosidase Inhibitors,http://dx.doi.org/10.3390/ijms11030880,PMC2869241,20479989,CC BY,"Andrographolide derivatives were shown to inhibit α-glucosidase. To investigate the relationship between activities and structures of andrographolide derivatives, a training set was chosen from 25 andrographolide derivatives by the principal component analysis (PCA) method, and a quantitative structure-activity relationship (QSAR) was established by 2D and 3D QSAR methods. The cross-validation r(2) (0.731) and standard error (0.225) illustrated that the 2D-QSAR model was able to identify the important molecular fragments and the cross-validation r(2) (0.794) and standard error (0.127) demonstrated that the 3D-QSAR model was capable of exploring the spatial distribution of important fragments. The obtained results suggested that proposed combination of 2D and 3D QSAR models could be useful in predicting the α-glucosidase inhibiting activity of andrographolide derivatives.",2010 Mar 2,"['Xu, Jun', 'Huang, Sichao', 'Luo, Haibin', 'Li, Guoji', 'Bao, Jiaolin', 'Cai, Shaohui', 'Wang, Yuqiang']",Int J Mol Sci,,,True
6522e893e7f5739f96db413b61932c949e5fad2d,PMC,A Single Immunization with Soluble Recombinant Trimeric Hemagglutinin Protects Chickens against Highly Pathogenic Avian Influenza Virus H5N1,http://dx.doi.org/10.1371/journal.pone.0010645,PMC2871037,20498717,CC BY,"BACKGROUND: The highly pathogenic avian influenza (HPAI) virus H5N1 causes multi-organ disease and death in poultry, resulting in significant economic losses in the poultry industry. In addition, it poses a major public health threat as it can be transmitted directly from infected poultry to humans with very high (60%) mortality rate. Effective vaccination against HPAI H5N1 would protect commercial poultry and would thus provide an important control measure by reducing the likelihood of bird-to-bird and bird-to-human transmission. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we evaluated the vaccine potential of recombinant soluble trimeric subtype 5 hemagglutinin (sH5(3)) produced in mammalian cells. The secreted, purified sH5(3) was biologically active as demonstrated by its binding to ligands in a sialic acid-dependent manner. It was shown to protect chickens, in a dose-dependent manner, against a lethal challenge with H5N1 after a single vaccination. Protected animals did not shed challenge virus as determined by a quantitative RT-PCR on RNA isolated from trachea and cloaca swabs. Also in mice, vaccination with sH5(3) provided complete protection against challenge with HPAI H5N1. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that sH5(3) constitutes an attractive vaccine antigen for protection of chickens and mammals against HPAI H5N1. As these recombinant soluble hemagglutinin preparations can be produced with high yields and with relatively short lead time, they enable a rapid response to circulating and potentially pandemic influenza viruses.",2010 May 14,"['Cornelissen, Lisette A. H. M.', 'de Vries, Robert P.', 'de Boer-Luijtze, Els A.', 'Rigter, Alan', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.']",PLoS One,,,True
b747413330a7699f64ee1acbc773808fba975fb3,PMC,Hospital Triage System for Adult Patients Using an Influenza-Like Illness Scoring System during the 2009 Pandemic—Mexico,http://dx.doi.org/10.1371/journal.pone.0010658,PMC2871038,20498718,CC0,"BACKGROUND: Pandemic influenza A (H1N1) virus emerged during 2009. To help clinicians triage adults with acute respiratory illness, a scoring system for influenza-like illness (ILI) was implemented at Hospital Civil de Guadalajara, Mexico. METHODS: A medical history, laboratory and radiology results were collected on emergency room (ER) patients with acute respiratory illness to calculate an ILI-score. Patients were evaluated for admission by their ILI-score and clinicians' assessment of risk for developing complications. Nasal and throat swabs were collected from intermediate and high-risk patients for influenza testing by RT-PCR. The disposition and ILI-score of those oseltamivir-treated versus untreated, clinical characteristics of 2009 pandemic influenza A (H1N1) patients versus test-negative patients were compared by Pearson's Χ(2), Fisher's Exact, and Wilcoxon rank-sum tests. RESULTS: Of 1840 ER patients, 230 were initially hospitalized (mean ILI-score = 15), and the rest were discharged, including 286 ambulatory patients given oseltamivir (median ILI-score = 11), and 1324 untreated (median ILI-score = 5). Fourteen (1%) untreated patients returned, and 3 were hospitalized on oseltamivir (median ILI-score  = 19). Of 371 patients tested by RT-PCR, 104 (28%) had pandemic influenza and 42 (11%) had seasonal influenza A detected. Twenty (91%) of 22 imaged hospitalized pandemic influenza patients had bilateral infiltrates compared to 23 (38%) of 61 imaged hospital test-negative patients (p<0.001). One patient with confirmed pandemic influenza presented 6 days after symptom onset, required mechanical ventilation, and died. CONCLUSIONS: The triaging system that used an ILI-score complimented clinicians' judgment of who needed oseltamivir and inpatient care and helped hospital staff manage a surge in demand for services.",2010 May 14,"['Rodriguez-Noriega, Eduardo', 'Gonzalez-Diaz, Esteban', 'Morfin-Otero, Rayo', 'Gomez-Abundis, Gerardo F.', 'Briseño-Ramirez, Jaime', 'Perez-Gomez, Hector Raul', 'Lopez-Gatell, Hugo', 'Alpuche-Aranda, Celia M.', 'Ramírez, Ernesto', 'López, Irma', 'Iguala, Miguel', 'Chapela, Ietza Bojórquez', 'Zavala, Ethel Palacios', 'Hernández, Mauricio', 'Stuart, Tammy L.', 'Villarino, Margarita Elsa', 'Widdowson, Marc-Alain', 'Waterman, Steve', 'Uyeki, Timothy', 'Azziz-Baumgartner, Eduardo', None, None]",PLoS One,,,True
3ed3ca15292f7b5c1ace98e0cece9a60609d8138,PMC,CEACAM1 recognition by bacterial pathogens is species-specific,http://dx.doi.org/10.1186/1471-2180-10-117,PMC2871271,20406467,CC BY,"BACKGROUND: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), an immunoglobulin (Ig)-related glycoprotein, serves as cellular receptor for a variety of Gram-negative bacterial pathogens associated with the human mucosa. In particular, Neisseria gonorrhoeae, N. meningitidis, Moraxella catarrhalis, and Haemophilus influenzae possess well-characterized CEACAM1-binding adhesins. CEACAM1 is typically involved in cell-cell attachment, epithelial differentiation, neovascularisation and regulation of T-cell proliferation, and is one of the few CEACAM family members with homologues in different mammalian lineages. However, it is unknown whether bacterial adhesins of human pathogens can recognize CEACAM1 orthologues from other mammals. RESULTS: Sequence comparisons of the amino-terminal Ig-variable-like domain of CEACAM1 reveal that the highest sequence divergence between human, murine, canine and bovine orthologues is found in the β-strands comprising the bacteria-binding CC'FG-face of the Ig-fold. Using GFP-tagged, soluble amino-terminal domains of CEACAM1, we demonstrate that bacterial pathogens selectively associate with human, but not other mammalian CEACAM1 orthologues. Whereas full-length human CEACAM1 can mediate internalization of Neisseria gonorrhoeae in transfected cells, murine CEACAM1 fails to support bacterial internalization, demonstrating that the sequence divergence of CEACAM1 orthologues has functional consequences with regard to bacterial recognition and cellular invasion. CONCLUSIONS: Our results establish the selective interaction of several human-restricted bacterial pathogens with human CEACAM1 and suggest that co-evolution of microbial adhesins with their corresponding receptors on mammalian cells contributes to the limited host range of these highly adapted infectious agents.",2010 Apr 20,"['Voges, Maike', 'Bachmann, Verena', 'Kammerer, Robert', 'Gophna, Uri', 'Hauck, Christof R']",BMC Microbiol,,,True
4922ec2dbaef5cf37c816d3b8bf8ef2003466949,PMC,The Impact of Schistosoma japonicum Infection and Treatment on Ultrasound-Detectable Morbidity: A Five-Year Cohort Study in Southwest China,http://dx.doi.org/10.1371/journal.pntd.0000685,PMC2872638,20502515,CC BY,"BACKGROUND: Ultrasonography allows for non-invasive examination of the liver and spleen and can further our understanding of schistosomiasis morbidity. METHODOLOGY/PRINCIPAL FINDINGS: We followed 578 people in Southwest China for up to five years. Participants were tested for Schistosoma japonicum infection in stool and seven standard measures of the liver and spleen were obtained using ultrasound to evaluate the relationship between schistosomiasis infection and ultrasound-detectable pathology, and the impact of targeted treatment on morbidity. Parenchymal fibrosis, a network pattern of the liver unique to S. japonicum, was associated with infection at the time of ultrasound (OR 1.40, 95% CI: 1.03–1.90) and infection intensity (test for trend, p = 0.002), adjusting for age, sex and year, and more strongly associated with prior infection status and intensity (adjusted OR 1.84, 95% CI: 1.30–2.60; test for trend: p<0.001 respectively), despite prompt treatment of infections. While declines in parenchymal fibrosis over time were statistically significant, only 28% of individuals with severe parenchymal fibrosis (grades 2 or 3) at enrollment reversed to normal or grade 1 within five years. Other liver abnormalities were less consistently associated with S. japonicum infection. CONCLUSIONS/SIGNIFICANCE: Parenchymal fibrosis is an appropriate measure of S. japonicum morbidity and can document reductions in disease following control efforts. Other ultrasound measures may have limited epidemiological value in regions with similar infection levels. Because severe fibrosis may not reverse quickly following treatment, efforts to reduce exposure to S. japonicum should be considered in combination with treatment to prevent schistosomiasis morbidity.",2010 May 18,"['Carlton, Elizabeth J.', 'Hsiang, Michelle', 'Zhang, Yi', 'Johnson, Sarah', 'Hubbard, Alan', 'Spear, Robert C.']",PLoS Negl Trop Dis,,,True
2246e28681bde69c65dc9081df367bb661997f19,PMC,"Secondary Syphilis in Cali, Colombia: New Concepts in Disease Pathogenesis",http://dx.doi.org/10.1371/journal.pntd.0000690,PMC2872645,20502522,CC0,"Venereal syphilis is a multi-stage, sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum (Tp). Herein we describe a cohort of 57 patients (age 18–68 years) with secondary syphilis (SS) identified through a network of public sector primary health care providers in Cali, Colombia. To be eligible for participation, study subjects were required to have cutaneous lesions consistent with SS, a reactive Rapid Plasma Reagin test (RPR-titer ≥1∶4), and a confirmatory treponemal test (Fluorescent Treponemal Antibody Absorption test- FTA-ABS). Most subjects enrolled were women (64.9%), predominantly Afro-Colombian (38.6%) or mestizo (56.1%), and all were of low socio-economic status. Three (5.3%) subjects were newly diagnosed with HIV infection at study entry. The duration of signs and symptoms in most patients (53.6%) was less than 30 days; however, some patients reported being symptomatic for several months (range 5–240 days). The typical palmar and plantar exanthem of SS was the most common dermal manifestation (63%), followed by diffuse hypo- or hyperpigmented macules and papules on the trunk, abdomen and extremities. Three patients had patchy alopecia. Whole blood (WB) samples and punch biopsy material from a subset of SS patients were assayed for the presence of Tp DNA polymerase I gene (polA) target by real-time qualitative and quantitative PCR methods. Twelve (46%) of the 26 WB samples studied had quantifiable Tp DNA (ranging between 194.9 and 1954.2 Tp polA copies/ml blood) and seven (64%) were positive when WB DNA was extracted within 24 hours of collection. Tp DNA was also present in 8/12 (66%) skin biopsies available for testing. Strain typing analysis was attempted in all skin and WB samples with detectable Tp DNA. Using arp repeat size analysis and tpr RFLP patterns four different strain types were identified (14d, 16d, 13d and 22a). None of the WB samples had sufficient DNA for typing. The clinical and microbiologic observations presented herein, together with recent Cali syphilis seroprevalence data, provide additional evidence that venereal syphilis is highly endemic in this region of Colombia, thus underscoring the need for health care providers in the region to be acutely aware of the clinical manifestations of SS. This study also provides, for the first time, quantitative evidence that a significant proportion of untreated SS patients have substantial numbers of circulating spirochetes. How Tp is able to persist in the blood and skin of SS patients, despite the known presence of circulating treponemal opsonizing antibodies and the robust pro-inflammatory cellular immune responses characteristic of this stage of the disease, is not fully understood and requires further study.",2010 May 18,"['Cruz, Adriana R.', 'Pillay, Allan', 'Zuluaga, Ana V.', 'Ramirez, Lady G.', 'Duque, Jorge E.', 'Aristizabal, Gloria E.', 'Fiel-Gan, Mary D.', 'Jaramillo, Roberto', 'Trujillo, Rodolfo', 'Valencia, Carlos', 'Jagodzinski, Linda', 'Cox, David L.', 'Radolf, Justin D.', 'Salazar, Juan C.']",PLoS Negl Trop Dis,,,True
759978859d988aaba2d6dcfde90663d797f89550,PMC,Reduction of Natural Killer but Not Effector CD8 T Lymphoyctes in Three Consecutive Cases of Severe/Lethal H1N1/09 Influenza A Virus Infection,http://dx.doi.org/10.1371/journal.pone.0010675,PMC2872666,20502691,CC BY,"BACKGROUND: The cause of severe disease in some patients infected with pandemic influenza A virus is unclear. METHODOLOGY/PRINCIPAL FINDINGS: We present the cellular immunology profile in the blood, and detailed clinical (and post-mortem) findings of three patients with rapidly progressive infection, including a pregnant patient who died. The striking finding is of reduction in natural killer (NK) cells but preservation of activated effector CD8 T lymphocytes; with viraemia in the patient who had no NK cells. Comparison with control groups suggests that the reduction of NK cells is unique to these severely ill patients. CONCLUSION/SIGNIFICANCE: Our report shows markedly reduced NK cells in the three patients that we sampled and raises the hypothesis that NK may have a more significant role than T lymphocytes in controlling viral burden when the host is confronted with a new influenza A virus subtype.",2010 May 18,"['Denney, Laura', 'Aitken, Celia', 'Li, Chris Ka-Fai', 'Wilson-Davies, Eleri', 'Kok, Wai Ling', 'Clelland, Colin', 'Rooney, Kevin', 'Young, Duncan', 'Dong, Tao', 'McMichael, Andrew J.', 'Carman, William F.', 'Ho, Ling-Pei']",PLoS One,,,True
43eaa4d7209e389a360aeab2b3b44e76fd89f5c2,PMC,An evaluation of potential reference genes for stability of expression in two salmonid cell lines after infection with either Piscirickettsia salmonis or IPNV,http://dx.doi.org/10.1186/1756-0500-3-101,PMC2873344,20398263,CC BY,"BACKGROUND: Due to the limited number of species specific antibodies against fish proteins, differential gene expression analyses are vital for the study of host immune responses. Quantitative real-time reverse transcription PCR (qRT-PCR) is one of the most powerful tools for this purpose. Nevertheless, the accuracy of the method will depend on the careful selection of genes whose expression are stable and can be used as internal controls for a particular experimental setting. FINDINGS: The expression stability of five commonly used housekeeping genes [beta-actin (ACTB), elongation factor 1-alpha (EF1A), ubiquitin (UBQ), glyceraldehyd-3-phosphate dehydrogenase (GAPDH) and tubulin alpha (TUBA)] were monitored in salmonid cell lines CHSE-214 and RTS11 after infection with two of the most fastidious fish pathogens, the facultative bacterium Piscirickettsia salmonis and the aquabirnavirus IPNV (Infectious Pancreatic Necrosis Virus). After geNorm analysis, UBQ and EF1A appeared as the most stable, although EF1A was slightly upregulated at late stages of P. salmonis infection in RTS11. ACTB instead, showed a good performance in each case, being always considered within the three most stable genes of the panel. In contrast, infection-dependent differential regulation of GAPDH and TUBA was also demonstrated. CONCLUSION: Based on the data presented here with the cell culture models CHSE-214 and RTS11, we suggest the initial choice of UBQ, ACTB and EF1A as reference genes in qRT-PCR assays for studying the effect of P. salmonis and IPNV on the host immune response.",2010 Apr 14,"['Peña, Andrea A', 'Bols, Niels C', 'Marshall, Sergio H']",BMC Res Notes,,,True
0877aadd2c55095b8a663597fbb39150614f335e,PMC,Collection by trained pediatricians or parents of mid-turbinate nasal flocked swabs for the detection of influenza viruses in childhood,http://dx.doi.org/10.1186/1743-422X-7-85,PMC2873380,20433729,CC BY,"This study evaluated the efficiency of pediatric mid-turbinate nasal flocked swabs used by parents in 203 children aged 6 months to 5 years with signs and symptoms of respiratory disease. Two nasal samples were collected from each child in a randomised sequence: one by a trained pediatrician and one by a parent. The real-time polymerase chain reaction influenza virus detection rates were similar in the samples collected using the two methods (Cohen's kappa = 0.86), as were the cycle threshold values. In comparison with the pediatrician-collected samples, the sensitivity and specificity of the parental collections were respectively 89.3% (95% confidence interval [CI]: 77.8-100%) and 97.7% (95% CI: 95.5-100%), and the positive and negative predictive values were respectively 86.2% (95% CI: 73.7-95.1%) and 98.2% (95% CI: 96.4-100%). The children were significantly more satisfied with the parental collections (median values ± standard deviation, 1.59 ± 0.55 vs 3.51 ± 0.36; p < 0.0001). These findings show that mid-turbinate nasal flocked swabs specifically designed for infants and children can be used by parents without reducing the influenza virus detection rate. Moreover, the direct involvement of parents significantly increases patient acceptance, thus simplifying collection and suggesting that this novel swab design should be considered for epidemiological surveys and vaccine efficacy studies.",2010 Apr 30,"['Esposito, Susanna', 'Molteni, Claudio G', 'Daleno, Cristina', 'Valzano, Antonia', 'Tagliabue, Claudia', 'Galeone, Carlotta', 'Milani, Gregorio', 'Fossali, Emilio', 'Marchisio, Paola', 'Principi, Nicola']",Virol J,,,True
3c1893f7c0ec143b4f173980381354e5cfe6416f,PMC,"Risk Factors for SARS Transmission from Patients Requiring Intubation: A Multicentre Investigation in Toronto, Canada",http://dx.doi.org/10.1371/journal.pone.0010717,PMC2873403,20502660,CC BY,"BACKGROUND: In the 2003 Toronto SARS outbreak, SARS-CoV was transmitted in hospitals despite adherence to infection control procedures. Considerable controversy resulted regarding which procedures and behaviours were associated with the greatest risk of SARS-CoV transmission. METHODS: A retrospective cohort study was conducted to identify risk factors for transmission of SARS-CoV during intubation from laboratory confirmed SARS patients to HCWs involved in their care. All SARS patients requiring intubation during the Toronto outbreak were identified. All HCWs who provided care to intubated SARS patients during treatment or transportation and who entered a patient room or had direct patient contact from 24 hours before to 4 hours after intubation were eligible for this study. Data was collected on patients by chart review and on HCWs by interviewer-administered questionnaire. Generalized estimating equation (GEE) logistic regression models and classification and regression trees (CART) were used to identify risk factors for SARS transmission. RESULTS: 45 laboratory-confirmed intubated SARS patients were identified. Of the 697 HCWs involved in their care, 624 (90%) participated in the study. SARS-CoV was transmitted to 26 HCWs from 7 patients; 21 HCWs were infected by 3 patients. In multivariate GEE logistic regression models, presence in the room during fiberoptic intubation (OR = 2.79, p = .004) or ECG (OR = 3.52, p = .002), unprotected eye contact with secretions (OR = 7.34, p = .001), patient APACHE II score ≥20 (OR = 17.05, p = .009) and patient Pa0(2)/Fi0(2) ratio ≤59 (OR = 8.65, p = .001) were associated with increased risk of transmission of SARS-CoV. In CART analyses, the four covariates which explained the greatest amount of variation in SARS-CoV transmission were covariates representing individual patients. CONCLUSION: Close contact with the airway of severely ill patients and failure of infection control practices to prevent exposure to respiratory secretions were associated with transmission of SARS-CoV. Rates of transmission of SARS-CoV varied widely among patients.",2010 May 19,"['Raboud, Janet', 'Shigayeva, Altynay', 'McGeer, Allison', 'Bontovics, Erika', 'Chapman, Martin', 'Gravel, Denise', 'Henry, Bonnie', 'Lapinsky, Stephen', 'Loeb, Mark', 'McDonald, L. Clifford', 'Ofner, Marianna', 'Paton, Shirley', 'Reynolds, Donna', 'Scales, Damon', 'Shen, Sandy', 'Simor, Andrew', 'Stewart, Thomas', 'Vearncombe, Mary', 'Zoutman, Dick', 'Green, Karen']",PLoS One,,,True
da2b69c89152ddb6f2df6c836bd84aebba2a0b65,PMC,Transcriptome sequencing and development of an expression microarray platform for the domestic ferret,http://dx.doi.org/10.1186/1471-2164-11-251,PMC2873475,20403183,CC BY,"BACKGROUND: The ferret (Mustela putorius furo) represents an attractive animal model for the study of respiratory diseases, including influenza. Despite its importance for biomedical research, the number of reagents for molecular and immunological analysis is restricted. We present here a parallel sequencing effort to produce an extensive EST (expressed sequence tags) dataset derived from a normalized ferret cDNA library made from mRNA from ferret blood, liver, lung, spleen and brain. RESULTS: We produced more than 500000 sequence reads that were assembled into 16000 partial ferret genes. These genes were combined with the available ferret sequences in the GenBank to develop a ferret specific microarray platform. Using this array, we detected tissue specific expression patterns which were confirmed by quantitative real time PCR assays. We also present a set of 41 ferret genes with even transcription profiles across the tested tissues, indicating their usefulness as housekeeping genes. CONCLUSION: The tools developed in this study allow for functional genomic analysis and make further development of reagents for the ferret model possible.",2010 Apr 19,"['Bruder, Carl E', 'Yao, Suxia', 'Larson, Francis', 'Camp, Jeremy V', 'Tapp, Ronald', 'McBrayer, Alexis', 'Powers, Nicholas', 'Valdivia Granda, Willy', 'Jonsson, Colleen B']",BMC Genomics,,,True
a762208186ddb3827966e6d7bec5a4fb8a0124cf,PMC,Treatment with Imiquimod enhances antitumor immunity induced by therapeutic HPV DNA vaccination,http://dx.doi.org/10.1186/1423-0127-17-32,PMC2873498,20426849,CC BY,"BACKGROUND: There is an urgent need to develop new innovative therapies for the control of advanced cancer. The combination of antigen-specific immunotherapy with the employment of immunomodulatory agents has emerged as a potentially plausible approach for the control of advanced cancer. METHODS: In the current study, we explored the combination of the DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 (HPV-16) E7 antigen (CRT/E7) with the TLR7 agonist imiquimod for their ability to generate E7-specific immune responses and antitumor effects in tumor-bearing mice. RESULTS: We observed that treatment with CRT/E7 DNA in combination with imiquimod leads to an enhancement in the E7-specific CD8+ T cell immune responses and a decrease in the number of myeloid-derived suppressor cells in the tumor microenvironment of tumor-bearing mice. Furthermore, treatment with CRT/E7 DNA in combination with imiquimod leads to significantly improved antitumor effects and prolonged survival in treated mice. In addition, treatment with imiquimod led to increased number of NK1.1+ cells and F4/80+ cells in the tumor microenvironment. Macrophages and NK1.1+ cells were found to play an important role in the antitumor effects mediated by treatment with CRT/E7 DNA in combination with imiquimod. CONCLUSIONS: Thus, our data suggests that the combination of therapeutic HPV DNA vaccination with topical treatment with the TLR7 agonist imiquimod enhances the antitumor immunity induced by DNA vaccination. The current study has significant implications for future clinical translation.",2010 Apr 28,"['Chuang, Chi-Mu', 'Monie, Archana', 'Hung, Chien-Fu', 'Wu, T-C']",J Biomed Sci,,,True
0469d052ac583aa5b739be7fedecec5307548d49,PMC,Perception of epidemic's related anxiety in the General French Population: a cross-sectional study in the Rhône-Alpes region,http://dx.doi.org/10.1186/1471-2458-10-191,PMC2874530,20385030,CC BY,"BACKGROUND: To efficiently plan appropriate public health interventions during possible epidemics, governments must take into consideration the following factors about the general population: their knowledge of epidemics, their fears of and psychological responses to them, their level of compliance with government measures and their communities' trusted sources of information. However, such surveys among the French general population are rare. METHODS: A cross-sectional study was conducted in 2006 in a representative sample of 600 subjects living in the Rhône-Alpes region (south-east France) to investigate self-reported knowledge about infectious diseases and anxiety generated by epidemic risk with particular reference to avian influenza. Data on reactions to potentially new epidemics and the confidence level in various sources of information were also collected. RESULTS: Respondents were most knowledgeable about AIDS, followed by avian influenza. Overall, 75% of respondents had adequate knowledge of avian influenza. The percentage was even higher (88%) among inhabitants of the Ain district, where an avian influenza epidemic had previously been reported. However, 39% expressed anxiety about this disease. In total, 20% of respondents with knowledge about avian influenza stated that they had changed their behaviours during the epizooty. Epidemics were perceived as a real threat by 27% of respondents. In the event of a highly contagious outbreak, the majority of respondents said they would follow the advice given by authorities. The study population expressed a high level of confidence in physicians and scientists, but had strong reservations about politicians, deputies and the media. CONCLUSIONS: Although the survey was conducted only four months after the avian influenza outbreak, epidemics were not perceived as a major threat by the study population. The results showed that in the event of a highly infectious disease, the population would comply with advice given by public authorities.",2010 Apr 13,"['Saadatian-Elahi, Mitra', 'Facy, Françoise', 'Del Signore, Corinne', 'Vanhems, Philippe']",BMC Public Health,,,True
008c1ceaeffe7abc87b031af39fae2632fa72897,PMC,AMS 3.0: prediction of post-translational modifications,http://dx.doi.org/10.1186/1471-2105-11-210,PMC2874555,20423529,CC BY,"BACKGROUND: We present here the recent update of AMS algorithm for identification of post-translational modification (PTM) sites in proteins based only on sequence information, using artificial neural network (ANN) method. The query protein sequence is dissected into overlapping short sequence segments. Ten different physicochemical features describe each amino acid; therefore nine residues long segment is represented as a point in a 90 dimensional space. The database of sequence segments with confirmed by experiments post-translational modification sites are used for training a set of ANNs. RESULTS: The efficiency of the classification for each type of modification and the prediction power of the method is estimated here using recall (sensitivity), precision values, the area under receiver operating characteristic (ROC) curves and leave-one-out tests (LOOCV). The significant differences in the performance for differently optimized neural networks are observed, yet the AMS 3.0 tool integrates those heterogeneous classification schemes into the single consensus scheme, and it is able to boost the precision and recall values independent of a PTM type in comparison with the currently available state-of-the art methods. CONCLUSIONS: The standalone version of AMS 3.0 presents an efficient way to indentify post-translational modifications for whole proteomes. The training datasets, precompiled binaries for AMS 3.0 tool and the source code are available at http://code.google.com/p/automotifserver under the Apache 2.0 license scheme.",2010 Apr 28,"['Basu, Subhadip', 'Plewczynski, Dariusz']",BMC Bioinformatics,,,True
a533da998e4132f8192e41a197f5d8cd065df996,PMC,"Journals, Academics, and Pandemics",http://dx.doi.org/10.1371/journal.pmed.1000282,PMC2876121,20520802,CC BY,"In the wake of the SARS epidemic and the H1N1 pandemic, the PLoS Medicine editors ask whether journal publishing is an efficient enough mechanism for information sharing.",2010 May 25,,PLoS Med,,,True
e12e72939bfeb49c8865a15d0c1bc9a4f99c0ece,PMC,Rotavirus Structural Proteins and dsRNA Are Required for the Human Primary Plasmacytoid Dendritic Cell IFNα Response,http://dx.doi.org/10.1371/journal.ppat.1000931,PMC2880586,20532161,CC BY,"Rotaviruses are the leading cause of severe dehydrating diarrhea in children worldwide. Rotavirus-induced immune responses, especially the T and B cell responses, have been extensively characterized; however, little is known about innate immune mechanisms involved in the control of rotavirus infection. Although increased levels of systemic type I interferon (IFNα and β) correlate with accelerated resolution of rotavirus disease, multiple rotavirus strains, including rhesus rotavirus (RRV), have been demonstrated to antagonize type I IFN production in a variety of epithelial and fibroblast cell types through several mechanisms, including degradation of multiple interferon regulatory factors by a viral nonstructural protein. This report demonstrates that stimulation of highly purified primary human peripheral plasmacytoid dendritic cells (pDCs) with either live or inactivated RRV induces substantial IFNα production by a subset of pDCs in which RRV does not replicate. Characterization of pDC responses to viral stimulus by flow cytometry and Luminex revealed that RRV replicates in a small subset of human primary pDCs and, in this RRV-permissive small subset, IFNα production is diminished. pDC activation and maturation were observed independently of viral replication and were enhanced in cells in which virus replicates. Production of IFNα by pDCs following RRV exposure required viral dsRNA and surface proteins, but neither viral replication nor activation by trypsin cleavage of VP4. These results demonstrate that a minor subset of purified primary human peripheral pDCs are permissive to RRV infection, and that pDCs retain functionality following RRV stimulus. Additionally, this study demonstrates trypsin-independent infection of primary peripheral cells by rotavirus, which may allow for the establishment of extraintestinal viremia and antigenemia. Importantly, these data provide the first evidence of IFNα induction in primary human pDCs by a dsRNA virus, while simultaneously demonstrating impaired IFNα production in primary human cells in which RRV replicates. Rotavirus infection of primary human pDCs provides a powerful experimental system for the study of mechanisms underlying pDC-mediated innate immunity to viral infection and reveals a potentially novel dsRNA-dependent pathway of IFNα induction.",2010 Jun 3,"['Deal, Emily M.', 'Jaimes, Maria C.', 'Crawford, Sue E.', 'Estes, Mary K.', 'Greenberg, Harry B.']",PLoS Pathog,,,True
8a05548f8c34051d47f568ce2135978de0f9515d,PMC,A multiplex reverse transcription-nested polymerase chain reaction for detection and differentiation of wild-type and vaccine strains of canine distemper virus,http://dx.doi.org/10.1186/1743-422X-7-86,PMC2880969,20433759,CC BY,"A multiplex reverse transcription-nested polymerase chain reaction (RT-nPCR) method was developed for the detection and differentiation of wild-type and vaccine strains of canine distemper virus (CDV). A pair of primers (P1 and P4) specific for CDV corresponding to the highly conserved region of the CDV genome were used as a common primer pair in the first-round PCR of the nested PCR. Primers P2 specific for CDV wild-type strains, were used as the forward primer together with the common reverse primer P4 in the second round of nested PCR. Primers P3, P5 specific for CDV wild-type strain or vaccine strain, were used as the forward primer together with the common reverse primer P4+P6 in the second round of nested PCR. A fragment of 177 bp was amplified from vaccine strain genomic RNA, and a fragment of 247 bp from wild-type strain genomic RNA in the RT-nPCR, and two fragments of 247 bp and 177 bp were amplified from the mixed samples of vaccine and wild-type strains. No amplification was achieved for uninfected cells, or cells infected with Newcastle disease virus (NDV), canine parvovirus (CPV), canine coronavirus (CCV), rabies virus (RV), or canine adenovirus (CAV). The RT-nPCR method was used to detect 30 field samples suspected of canine distemper from Heilongjiang and Jilin Provinces, and 51 samples in Shandong province. As a result of 30 samples, were found to be wild-type-like, and 5 to be vaccine-strain-like. The RT-nPCR method can be used to effectively detect and differentiate wild-type CDV-infected dogs from dogs vaccinated with CDV vaccine, and thus can be used in clinical detection and epidemiological surveillance.",2010 May 1,"['Si, Wei', 'Zhou, Shun', 'Wang, Zhao', 'Cui, Shang-jin']",Virol J,,,True
a71e4139dc4ba7ca03da5d99cac0781f092d5223,PMC,Rapid semi-automated quantitative multiplex tandem PCR (MT-PCR) assays for the differential diagnosis of influenza-like illness,http://dx.doi.org/10.1186/1471-2334-10-113,PMC2881921,20459845,CC BY,"BACKGROUND: Influenza A, including avian influenza, is a major public health threat in developed and developing countries. Rapid and accurate detection is a key component of strategies to contain spread of infection, and the efficient diagnosis of influenza-like-illness is essential to protect health infrastructure in the event of a major influenza outbreak. METHODS: We developed a multiplexed PCR (MT-PCR) assay for the simultaneous diagnosis of respiratory viruses causing influenza-like illness, including the specific recognition of influenza A haemagglutinin subtypes H1, H3, and H5. We tested several hundred clinical specimens in two diagnostic reference laboratories and compared the results with standard techniques. RESULTS: The sensitivity and specificity of these assays was higher than individual assays based on direct antigen detection and standard PCR against a range of control templates and in several hundred clinical specimens. The MT-PCR assays provided differential diagnoses as well as potentially useful quantitation of virus in clinical samples. CONCLUSIONS: MT-PCR is a potentially powerful tool for the differential diagnosis of influenza-like illness in the clinical diagnostic laboratory.",2010 May 11,"['Szewczuk, Elektra', 'Thapa, Kiran', 'Anninos, Terry', 'McPhie, Kenneth', 'Higgins, Geoff', 'Dwyer, Dominic E', 'Stanley, Keith K', 'Iredell, Jonathan R']",BMC Infect Dis,,,True
926d8dc84a667e11dfea30fac3824fd17e175398,PMC,A Crucial Role for Infected-Cell/Antibody Immune Complexes in the Enhancement of Endogenous Antiviral Immunity by Short Passive Immunotherapy,http://dx.doi.org/10.1371/journal.ppat.1000948,PMC2883599,20548955,CC BY,"Antiviral monoclonal antibodies (mAbs) represent promising therapeutics. However, most mAbs-based immunotherapies conducted so far have only considered the blunting of viral propagation and not other possible therapeutic effects independent of virus neutralization, namely the modulation of the endogenous immune response. As induction of long-term antiviral immunity still remains a paramount challenge for treating chronic infections, we have asked here whether neutralizing mAbs can, in addition to blunting viral propagation, exert immunomodulatory effects with protective outcomes. Supporting this idea, we report here that mice infected with the FrCas(E) murine retrovirus on day 8 after birth die of leukemia within 4–5 months and mount a non-protective immune response, whereas those rapidly subjected to short immunotherapy with a neutralizing mAb survive healthy and mount a long-lasting protective antiviral immunity with strong humoral and cellular immune responses. Interestingly, the administered mAb mediates lysis of infected cells through an antibody-dependent cell cytotoxicity (ADCC) mechanism. In addition, it forms immune complexes (ICs) with infected cells that enhance antiviral CTL responses through FcγR-mediated binding to dendritic cells (DCs). Importantly, the endogenous antiviral antibodies generated in mAb-treated mice also display the same properties, allowing containment of viral propagation and enhancement of memory cellular responses after disappearance of the administered mAb. Thus, our data demonstrate that neutralizing antiviral mAbs can act as immunomodulatory agents capable of stimulating a protective immunity lasting long after the end of the treatment. They also show an important role of infected-cells/antibody complexes in the induction and the maintenance of protective immunity through enhancement of both primary and memory antiviral T-cell responses. They also indicate that targeting infected cells, and not just viruses, by antibodies can be crucial for elicitation of efficient, long-lasting antiviral T-cell responses. This must be considered when designing antiviral mAb-based immunotherapies.",2010 Jun 10,"['Michaud, Henri-Alexandre', 'Gomard, Tiphanie', 'Gros, Laurent', 'Thiolon, Kevin', 'Nasser, Roudaina', 'Jacquet, Chantal', 'Hernandez, Javier', 'Piechaczyk, Marc', 'Pelegrin, Mireia']",PLoS Pathog,,,True
dbe74afc075c179f7c6298934ce53e6e6bdae4ea,PMC,Phylogenetic nomenclature and evolution of mannose-binding lectin (MBL2) haplotypes,http://dx.doi.org/10.1186/1471-2156-11-38,PMC2885306,20465856,CC BY,"BACKGROUND: Polymorphisms of the mannose-binding lectin gene (MBL2) affect the concentration and functional efficiency of the protein. We recently used haplotype-specific sequencing to identify 23 MBL2 haplotypes, associated with enhanced susceptibility to several diseases. RESULTS: In this work, we applied the same method in 288 and 470 chromosomes from Gabonese and European adults, respectively, and found three new haplotypes in the last group. We propose a phylogenetic nomenclature to standardize MBL2 studies and found two major phylogenetic branches due to six strongly linked polymorphisms associated with high MBL production. They presented high Fst values and were imbedded in regions with high nucleotide diversity and significant Tajima's D values. Compared to others using small sample sizes and unphased genotypic data, we found differences in haplotyping, frequency estimation, Fu and Li's D* and Fst results. CONCLUSION: Using extensive testing for selective neutrality, we confirmed that stochastic evolutionary factors have had a major role in shaping this polymorphic gene worldwide.",2010 May 14,"['Boldt, Angelica BW', 'Messias-Reason, Iara J', 'Meyer, Diogo', 'Schrago, Carlos G', 'Lang, Florian', 'Lell, Bertrand', 'Dietz, Klaus', 'Kremsner, Peter G', 'Petzl-Erler, Maria Luiza', 'Kun, Jürgen FJ']",BMC Genet,,,True
a5f1fd1f2782b89068dd76bde0acbffc35632895,PMC,"Incorporation of podoplanin into HIV released from HEK-293T cells, but not PBMC, is required for efficient binding to the attachment factor CLEC-2",http://dx.doi.org/10.1186/1742-4690-7-47,PMC2885308,20482880,CC BY,"BACKGROUND: Platelets are associated with HIV in the blood of infected individuals and might modulate viral dissemination, particularly if the virus is directly transmitted into the bloodstream. The C-type lectin DC-SIGN and the novel HIV attachment factor CLEC-2 are expressed by platelets and facilitate HIV transmission from platelets to T-cells. Here, we studied the molecular mechanisms behind CLEC-2-mediated HIV-1 transmission. RESULTS: Binding studies with soluble proteins indicated that CLEC-2, in contrast to DC-SIGN, does not recognize the viral envelope protein, but a cellular factor expressed on kidney-derived 293T cells. Subsequent analyses revealed that the cellular mucin-like membranous glycoprotein podoplanin, a CLEC-2 ligand, was expressed on 293T cells and incorporated into virions released from these cells. Knock-down of podoplanin in 293T cells by shRNA showed that virion incorporation of podoplanin was required for efficient CLEC-2-dependent HIV-1 interactions with cell lines and platelets. Flow cytometry revealed no evidence for podoplanin expression on viable T-cells and peripheral blood mononuclear cells (PBMC). Podoplanin was also not detected on HIV-1 infected T-cells. However, apoptotic bystander cells in HIV-1 infected cultures reacted with anti-podoplanin antibodies, and similar results were obtained upon induction of apoptosis in a cell line and in PBMCs suggesting an unexpected link between apoptosis and podoplanin expression. Despite the absence of detectable podoplanin expression, HIV-1 produced in PBMC was transmitted to T-cells in a CLEC-2-dependent manner, indicating that T-cells might express an as yet unidentified CLEC-2 ligand. CONCLUSIONS: Virion incorporation of podoplanin mediates CLEC-2 interactions of HIV-1 derived from 293T cells, while incorporation of a different cellular factor seems to be responsible for CLEC-2-dependent capture of PBMC-derived viruses. Furthermore, evidence was obtained that podoplanin expression is connected to apoptosis, a finding that deserves further investigation.",2010 May 19,"['Chaipan, Chawaree', 'Steffen, Imke', 'Tsegaye, Theodros Solomon', 'Bertram, Stephanie', 'Glowacka, Ilona', 'Kato, Yukinari', 'Schmökel, Jan', 'Münch, Jan', 'Simmons, Graham', 'Gerardy-Schahn, Rita', 'Pöhlmann, Stefan']",Retrovirology,,,True
34dfd4d983484d85d797e915cb47041aeb4ced86,PMC,An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of Hand Foot and Mouth Disease in Fuyang city of China,http://dx.doi.org/10.1186/1743-422X-7-94,PMC2885340,20459851,CC BY,"Hand, foot and mouth disease (HFMD), a common contagious disease that usually affects children, is normally mild but can have life-threatening manifestations. It can be caused by enteroviruses, particularly Coxsackieviruses and human enterovirus 71 (HEV71) with highly variable clinical manifestations. In the spring of 2008, a large, unprecedented HFMD outbreak in Fuyang city of Anhui province in the central part of southeastern China resulted in a high aggregation of fatal cases. In this study, epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak. Of the 6,049 cases reported between 1 March and 9 May of 2008, 3023 (50%) were hospitalized, 353 (5.8%) were severe and 22 (0.36%) were fatal. HEV71 was confirmed as the etiological pathogen of the outbreak. Phylogenetic analyses of entire VP1 capsid protein sequence of 45 Fuyang HEV71 isolates showed that they belong to C4a cluster of the C4 subgenotype. In addition, genetic recombinations were found in the 3D region (RNA-dependent RNA polymerase, a major component of the viral replication complex of the genome) between the Fuyang HEV71 strain and Coxsackievirus A16 (CV-A16), resulting in a recombination virus. In conclusion, an emerging recombinant HEV71 was responsible for the HFMD outbreak in Fuyang City of China, 2008.",2010 May 12,"['Zhang, Yan', 'Zhu, Zhen', 'Yang, Weizhong', 'Ren, Jun', 'Tan, Xiaojuan', 'Wang, Yu', 'Mao, Naiying', 'Xu, Songtao', 'Zhu, Shuangli', 'Cui, Aili', 'Zhang, Yong', 'Yan, Dongmei', 'Li, Qun', 'Dong, Xiaoping', 'Zhang, Jing', 'Zhao, Yueping', 'Wan, Junfeng', 'Feng, Zijian', 'Sun, Junling', 'Wang, Shiwen', 'Li, Dexin', 'Xu, Wenbo']",Virol J,,,True
b1b2eb98641f5fbf2b51cb26566196ae59a7ad96,PMC,Monitoring of risk perceptions and correlates of precautionary behaviour related to human avian influenza during 2006 - 2007 in the Netherlands: results of seven consecutive surveys,http://dx.doi.org/10.1186/1471-2334-10-114,PMC2885389,20462419,CC BY,"BACKGROUND: Avian influenza (AI) is a public health challenge because of ongoing spread and pandemic potential. Non-pharmaceutical measures are important to prevent the spread of AI and to contain a pandemic. The effectiveness of such measures is largely dependent on the behaviour of the population. Risk perception is a central element in changing behaviour. This study aimed to investigate perceived vulnerability, severity and precautionary behaviour related to AI in the Netherlands during seven consecutive surveys in 2006 - 2007 as well as possible trends in risk perception and self-reported precautionary behaviours. METHODS: Seven web-based surveys were conducted including 3,840 respondents over a one-year period. Time trends were analyzed with linear regression analyses. Multivariate analysis was used to study determinants of precautionary behaviour. RESULTS: While infection with AI was considered a very severe health problem with mean score of 4.57 (scale 1 - 5); perceived vulnerability was much lower, with a mean score of 1.69. While perceived severity remained high, perceived vulnerability decreased slightly during a one-year period covering part of 2006 and 2007. Almost half of the respondents (46%) reported taking one or more preventive measures, with 36% reporting to have stayed away from (wild) birds or poultry. In multivariate logistic regression analysis the following factors were significantly associated with taking preventive measures: time of the survey, higher age, lower level of education, non-Dutch ethnicity, vaccinated against influenza, higher perceived severity, higher perceived vulnerability, higher self efficacy, lower level of knowledge, more information about AI, and thinking more about AI. Self efficacy was a stronger predictor of precautionary behaviour for those who never or seldom think about AI (OR 2.3, 95% CI 1.9 - 2.7), compared to those who think about AI more often (OR 1.5, 95% CI 1.2 - 1.9). CONCLUSIONS: The fact that perceived severity of AI appears to be high and remains so over time offers a good point of departure for more specific risk communications to promote precautionary actions. Such communications should aim at improving knowledge about the disease and preventive actions, and focus on perceived personal vulnerability and self efficacy in taking preventive measures.",2010 May 12,"['de Zwart, Onno', 'Veldhuijzen, Irene K', 'Richardus, Jan Hendrik', 'Brug, Johannes']",BMC Infect Dis,,,True
351ea0aee67d40885b15698e3c38134f67590a9a,PMC,Serum 25-Hydroxyvitamin D and the Incidence of Acute Viral Respiratory Tract Infections in Healthy Adults,http://dx.doi.org/10.1371/journal.pone.0011088,PMC2885414,20559424,CC BY,"BACKGROUND: Declining serum concentrations of 25-hydroxyvitamin D seen in the fall and winter as distance increases from the equator may be a factor in the seasonal increased prevalence of influenza and other viral infections. This study was done to determine if serum 25-hydroxyvitamin D concentrations correlated with the incidence of acute viral respiratory tract infections. METHODOLOGY/FINDINGS: In this prospective cohort study serial monthly concentrations of 25-hydroxyvitamin D were measured over the fall and winter 2009–2010 in 198 healthy adults, blinded to the nature of the substance being measured. The participants were evaluated for the development of any acute respiratory tract infections by investigators blinded to the 25-hydroxyvitamin D concentrations. The incidence of infection in participants with different concentrations of vitamin D was determined. One hundred ninety-five (98.5%) of the enrolled participants completed the study. Light skin pigmentation, lean body mass, and supplementation with vitamin D were found to correlate with higher concentrations of 25-hydroxyvitamin D. Concentrations of 38 ng/ml or more were associated with a significant (p<0.0001) two-fold reduction in the risk of developing acute respiratory tract infections and with a marked reduction in the percentages of days ill. CONCLUSIONS/SIGNIFICANCE: Maintenance of a 25-hydroxyvitamin D serum concentration of 38 ng/ml or higher should significantly reduce the incidence of acute viral respiratory tract infections and the burden of illness caused thereby, at least during the fall and winter in temperate zones. The findings of the present study provide direction for and call for future interventional studies examining the efficacy of vitamin D supplementation in reducing the incidence and severity of specific viral infections, including influenza, in the general population and in subpopulations with lower 25-hydroxyvitamin D concentrations, such as pregnant women, dark skinned individuals, and the obese.",2010 Jun 14,"['Sabetta, James R.', 'DePetrillo, Paolo', 'Cipriani, Ralph J.', 'Smardin, Joanne', 'Burns, Lillian A.', 'Landry, Marie L.']",PLoS One,,,True
9bbf07c4bf022a0695b79b87cb4299f6a8d18831,PMC,EST analysis reveals putative genes involved in glycyrrhizin biosynthesis,http://dx.doi.org/10.1186/1471-2164-11-268,PMC2886062,20423525,CC BY,"BACKGROUND: Glycyrrhiza uralensis is one of the most popular medicinal plants in the world and is also widely used in the flavoring of food and tobacco. Due to limited genomic and transcriptomic data, the biosynthetic pathway of glycyrrhizin, the major bioactive compound in G. uralensis, is currently unclear. Identification of candidate genes involved in the glycyrrhizin biosynthetic pathway will significantly contribute to the understanding of the biosynthetic and medicinal chemistry of this compound. RESULTS: We used the 454 GS FLX platform and Titanium regents to produce a substantial expressed sequence tag (EST) dataset from the vegetative organs of G. uralensis. A total of 59,219 ESTs with an average read length of 409 bp were generated. 454 ESTs were combined with the 50,666 G. uralensis ESTs in GenBank. The combined ESTs were assembled into 27,229 unique sequences (11,694 contigs and 15,535 singletons). A total of 20,437 unique gene elements representing approximately 10,000 independent transcripts were annotated using BLAST searches (e-value ≤ 1e-5) against the SwissProt, KEGG, TAIR, Nr and Nt databases. The assembled sequences were annotated with gene names and Gene Ontology (GO) terms. With respect to the genes related to glycyrrhizin metabolism, genes encoding 16 enzymes of the 18 total steps of the glycyrrhizin skeleton synthesis pathway were found. To identify novel genes that encode cytochrome P450 enzymes and glycosyltransferases, which are related to glycyrrhizin metabolism, a total of 125 and 172 unigenes were found to be homologous to cytochrome P450s and glycosyltransferases, respectively. The cytochrome P450 candidate genes were classified into 32 CYP families, while the glycosyltransferase candidate genes were classified into 45 categories by GO analysis. Finally, 3 cytochrome P450 enzymes and 6 glycosyltransferases were selected as the candidates most likely to be involved in glycyrrhizin biosynthesis through an organ-specific expression pattern analysis based on real-time PCR. CONCLUSIONS: Using the 454 GS FLX platform and Titanium reagents, our study provides a high-quality EST database for G. uralensis. Based on the EST analysis, novel candidate genes related to the secondary metabolite pathway of glycyrrhizin, including novel genes encoding cytochrome P450s and glycosyltransferases, were found. With the assistance of organ-specific expression pattern analysis, 3 unigenes encoding cytochrome P450s and 6 unigenes encoding glycosyltransferases were selected as the candidates most likely to be involved in glycyrrhizin biosynthesis.",2010 Apr 28,"['Li, Ying', 'Luo, Hong-Mei', 'Sun, Chao', 'Song, Jing-Yuan', 'Sun, Yong-Zhen', 'Wu, Qiong', 'Wang, Ning', 'Yao, Hui', 'Steinmetz, André', 'Chen, Shi-Lin']",BMC Genomics,,,True
b0eabdda18ddcbe7d2c1ed0932ee123d7eb6dbbf,PMC,Investigating antibody neutralization of lyssaviruses using lentiviral pseudotypes: a cross-species comparison,http://dx.doi.org/10.1099/vir.0.2008/000349-0,PMC2886951,18753230,CC BY,"Cross-neutralization between rabies virus (RABV) and two European bat lyssaviruses (EBLV-1 and -2) was analysed using lentiviral pseudotypes as antigen vectors. Glycoprotein (G-protein) cDNA from RABV challenge virus standard-11 (CVS-11) and EBLV-1 and -2 were cloned and co-expressed with human immunodeficiency virus (HIV) or murine leukemia virus (MLV) gag–pol and packageable green fluorescent protein (GFP) or luciferase reporter genes in human cells. The harvested lentiviral (HIV) vector infected over 40 % of baby hamster kidney (BHK) target cells, providing high-titre pseudotype stocks. Tests on blinded antibody-positive (n=15) and -negative (n=45) sera, predetermined by the fluorescent antibody virus neutralization (FAVN) test approved by the World Health Organization (WHO) and Office International des Epizooties (OIE), revealed that the CVS-11 pseudotype assay had 100 % concordance with FAVN and strongly correlated with neutralization titres (r(2)=0.89). Cross-neutralization tests using sera from RABV-vaccinated humans and animals on pseudotypes with CVS-11, EBLV-1 and EBLV-2 envelopes showed that the relative neutralization titres correlated broadly with the degree of G-protein diversity. Pseudotypes have three major advantages over live-virus neutralization tests: (i) they can be handled in low-biohazard-level laboratories; (ii) the use of reporter genes such as GFP or β-galactosidase will allow the assay to be undertaken at low cost in laboratories worldwide; (iii) each assay requires <10 μl serum. This robust microassay will improve our understanding of the protective humoral immunity that current rabies vaccines confer against emerging lyssaviruses, and will be applicable to surveillance studies, thus helping to control the spread of rabies.",2008 Sep,"['Wright, Edward', 'Temperton, Nigel J.', 'Marston, Denise A.', 'McElhinney, Lorraine M.', 'Fooks, Anthony R.', 'Weiss, Robin A.']",J Gen Virol,,,True
0f258dbe201ef5c1419ecfceeb46634cd8451c8e,PMC,Investigating antibody neutralization of lyssaviruses using lentiviral pseudotypes: a cross-species comparison,http://dx.doi.org/10.1099/vir.0.2008/000349-0,PMC2886951,18753230,CC BY,"Cross-neutralization between rabies virus (RABV) and two European bat lyssaviruses (EBLV-1 and -2) was analysed using lentiviral pseudotypes as antigen vectors. Glycoprotein (G-protein) cDNA from RABV challenge virus standard-11 (CVS-11) and EBLV-1 and -2 were cloned and co-expressed with human immunodeficiency virus (HIV) or murine leukemia virus (MLV) gag–pol and packageable green fluorescent protein (GFP) or luciferase reporter genes in human cells. The harvested lentiviral (HIV) vector infected over 40 % of baby hamster kidney (BHK) target cells, providing high-titre pseudotype stocks. Tests on blinded antibody-positive (n=15) and -negative (n=45) sera, predetermined by the fluorescent antibody virus neutralization (FAVN) test approved by the World Health Organization (WHO) and Office International des Epizooties (OIE), revealed that the CVS-11 pseudotype assay had 100 % concordance with FAVN and strongly correlated with neutralization titres (r(2)=0.89). Cross-neutralization tests using sera from RABV-vaccinated humans and animals on pseudotypes with CVS-11, EBLV-1 and EBLV-2 envelopes showed that the relative neutralization titres correlated broadly with the degree of G-protein diversity. Pseudotypes have three major advantages over live-virus neutralization tests: (i) they can be handled in low-biohazard-level laboratories; (ii) the use of reporter genes such as GFP or β-galactosidase will allow the assay to be undertaken at low cost in laboratories worldwide; (iii) each assay requires <10 μl serum. This robust microassay will improve our understanding of the protective humoral immunity that current rabies vaccines confer against emerging lyssaviruses, and will be applicable to surveillance studies, thus helping to control the spread of rabies.",2008 Sep,"['Wright, Edward', 'Temperton, Nigel J.', 'Marston, Denise A.', 'McElhinney, Lorraine M.', 'Fooks, Anthony R.', 'Weiss, Robin A.']",J Gen Virol,,,False
d00f2e117b4d930186ab62bb1a94f929435f9aaf,PMC,Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2,http://dx.doi.org/10.1099/vir.0.2008/003962-0,PMC2886958,18931070,CC BY,"Although in different groups, the coronaviruses severe acute respiratory syndrome-coronavirus (SARS-CoV) and NL63 use the same receptor, angiotensin converting enzyme (ACE)-2, for entry into the host cell. Despite this common receptor, the consequence of entry is very different; severe respiratory distress in the case of SARS-CoV but frequently only a mild respiratory infection for NL63. Using a wholly recombinant system, we have investigated the ability of each virus receptor-binding protein, spike or S protein, to bind to ACE-2 in solution and on the cell surface. In both assays, we find that the NL63 S protein has a weaker interaction with ACE-2 than the SARS-CoV S protein, particularly in solution binding, but the residues required for contact are similar. We also confirm that the ACE-2-binding site of NL63 S lies between residues 190 and 739. A lower-affinity interaction with ACE-2 might partly explain the different pathological consequences of infection by SARS-CoV and NL63.",2008 Nov,"['Mathewson, Alison C.', 'Bishop, Alexandra', 'Yao, Yongxiu', 'Kemp, Fred', 'Ren, Junyuan', 'Chen, Hongying', 'Xu, Xiaodong', 'Berkhout, Ben', 'van der Hoek, Lia', 'Jones, Ian M.']",J Gen Virol,,,True
f8f601687c9a9a4debc34112cec0165ad81fb15d,PMC,Immune Response to Lactobacillus plantarum Expressing Borrelia burgdorferi OspA Is Modulated by the Lipid Modification of the Antigen,http://dx.doi.org/10.1371/journal.pone.0011199,PMC2887847,20585451,CC BY,"BACKGROUND: Over the past decade there has been increasing interest in the use of lactic acid bacteria as mucosal delivery vehicles for vaccine antigens, microbicides and therapeutics. We investigated the mechanism by which a mucosal vaccine based in recombinant lactic acid bacteria breaks the immunological tolerance of the gut in order to elicit a protective immune response. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed how the lipid modification of OspA affects the localization of the antigen in our delivery vehicle using a number of biochemistry techniques. Furthermore, we examined how OspA-expressing L. plantarum breaks the oral tolerance of the gut by stimulating human intestinal epithelial cells, peripheral blood mononuclear cells and monocyte derived dendritic cells and measuring cytokine production. We show that the leader peptide of OspA targets the protein to the cell envelope of L. plantarum, and it is responsible for protein export across the membrane. Mutation of the lipidation site in OspA redirects protein localization within the cell envelope. Further, we show that lipidated-OspA-expressing L. plantarum does not induce secretion of the pro-inflammatory cytokine IL-8 by intestinal epithelial cells. In addition, it breaks oral tolerance of the gut via Th1/Th2 cell mediated immunity, as shown by the production of pro- and anti-inflammatory cytokines by human dendritic cells, and by the production of IgG2a and IgG1 antibodies, respectively. CONCLUSIONS/SIGNIFICANCE: Lipid modification of OspA expressed in L. plantarum modulates the immune response to this antigen through a Th1/Th2 immune response.",2010 Jun 18,"['del Rio, Beatriz', 'Seegers, Jos F. M. L.', 'Gomes-Solecki, Maria']",PLoS One,,,True
c498ea64810a8da9cb26c48e1f5e96973537338d,PMC,Imported Episodic Rabies Increases Patient Demand for and Physician Delivery of Antirabies Prophylaxis,http://dx.doi.org/10.1371/journal.pntd.0000723,PMC2889823,20582307,CC BY,"BACKGROUND: Imported cases threaten rabies reemergence in rabies-free areas. During 2000–2005, five dog and one human rabies cases were imported into France, a rabies-free country since 2001. The Summer 2004 event led to unprecedented media warnings by the French Public Health Director. We investigated medical practice evolution following the official elimination of rabies in 2001; impact of subsequent episodic rabies importations and national newspaper coverage on demand for and delivery of antirabies prophylaxis; regular transmission of epidemiological developments within the French Antirabies Medical Center (ARMC) network; and ARMC discussions on indications of rabies post-exposure prophylaxis (RPEP). METHODOLOGY/PRINCIPAL FINDINGS: Annual data collected by the National Reference Center for Rabies NRCR (1989–2006) and the exhaustive database (2000–2005) of 56 ARMC were analyzed. Weekly numbers of patients consulting at ARMC and their RPEP- and antirabies-immunoglobulin (ARIG) prescription rates were determined. Autoregressive integrated moving-average modeling and regression with autocorrelated errors were applied to examine how 2000–2005 episodic rabies events and their related national newspaper coverage affected demand for and delivery of RPEP. A slight, continuous decline of rabies-dedicated public health facility attendance was observed from 2000 to 2004. Then, during the Summer 2004 event, patient consultations and RPEP and ARIG prescriptions increased by 84%, 19.7% and 43.4%, respectively. Moreover, elevated medical resource use persisted in 2005, despite communication efforts, without any secondary human or animal case. CONCLUSIONS: Our findings demonstrated appropriate responsiveness to reemerging rabies cases and effective newspaper reporting, as no secondary case occurred. However, the ensuing demand on medical resources had immediate and long-lasting effects on rabies-related public health resources and expenses. Henceforth, when facing such an event, decision-makers must anticipate the broad impact of their media communications to counter the emerging risk on maintaining an optimal public health organization and implement a post-crisis communication strategy.",2010 Jun 22,"['Lardon, Zélie', 'Watier, Laurence', 'Brunet, Audrey', 'Bernède, Claire', 'Goudal, Maryvonne', 'Dacheux, Laurent', 'Rotivel, Yolande', 'Guillemot, Didier', 'Bourhy, Hervé']",PLoS Negl Trop Dis,,,True
f60263668f8bb59ae4bd30498e2f04c18157773e,PMC,Structural Optimization and De Novo Design of Dengue Virus Entry Inhibitory Peptides,http://dx.doi.org/10.1371/journal.pntd.0000721,PMC2889824,20582308,CC0,"Viral fusogenic envelope proteins are important targets for the development of inhibitors of viral entry. We report an approach for the computational design of peptide inhibitors of the dengue 2 virus (DENV-2) envelope (E) protein using high-resolution structural data from a pre-entry dimeric form of the protein. By using predictive strategies together with computational optimization of binding “pseudoenergies”, we were able to design multiple peptide sequences that showed low micromolar viral entry inhibitory activity. The two most active peptides, DN57opt and 1OAN1, were designed to displace regions in the domain II hinge, and the first domain I/domain II beta sheet connection, respectively, and show fifty percent inhibitory concentrations of 8 and 7 µM respectively in a focus forming unit assay. The antiviral peptides were shown to interfere with virus:cell binding, interact directly with the E proteins and also cause changes to the viral surface using biolayer interferometry and cryo-electron microscopy, respectively. These peptides may be useful for characterization of intermediate states in the membrane fusion process, investigation of DENV receptor molecules, and as lead compounds for drug discovery.",2010 Jun 22,"['Costin, Joshua M.', 'Jenwitheesuk, Ekachai', 'Lok, Shee-Mei', 'Hunsperger, Elizabeth', 'Conrads, Kelly A.', 'Fontaine, Krystal A.', 'Rees, Craig R.', 'Rossmann, Michael G.', 'Isern, Sharon', 'Samudrala, Ram', 'Michael, Scott F.']",PLoS Negl Trop Dis,,,True
f021d8bdb3482a6965a104dddb2516d179bd9c34,PMC,Hopefulness predicts resilience after hereditary colorectal cancer genetic testing: a prospective outcome trajectories study,http://dx.doi.org/10.1186/1471-2407-10-279,PMC2891641,20537192,CC BY,"BACKGROUND -: Genetic testing for hereditary colorectal cancer (HCRC) had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict psychological resilience in adults undergoing genetic testing for HCRC. METHODS -: A longitudinal study was carried out from April 2003 to August 2006 on Hong Kong Chinese HCRC family members who were recruited and offered genetic testing by the Hereditary Gastrointestinal Cancer Registry to determine psychological outcomes after genetic testing. Self-completed questionnaires were administered immediately before (pre-disclosure baseline) and 2 weeks, 4 months and 1 year after result disclosure. Using validated psychological inventories, the cognitive style of hope was measured at baseline, and the psychological distress of depression and anxiety was measured at all time points. RESULTS -: Of the 76 participating subjects, 71 individuals (43 men and 28 women; mean age 38.9 ± 9.2 years) from nine FAP and 24 HNPCC families completed the study, including 39 mutated gene carriers. Four patterns of outcome trajectories were created using established norms for the specified outcome measures of depression and anxiety. These included chronic dysfunction (13% and 8.7%), recovery (0% and 4.3%), delayed dysfunction (13% and 15.9%) and resilience (76.8% and 66.7%). Two logistic regression analyses were conducted using hope at baseline to predict resilience, with depression and anxiety employed as outcome indicators. Because of the small number of participants, the chronic dysfunction and delayed dysfunction groups were combined into a non-resilient group for comparison with the resilient group in all subsequent analysis. Because of low frequencies, participants exhibiting a recovery trajectory (n = 3 for anxiety and n = 0 for depression) were excluded from further analysis. Both regression equations were significant. Baseline hope was a significant predictor of a resilience outcome trajectory for depression (B = -0.24, p < 0.01 for depression); and anxiety (B = -0.11, p = 0.05 for anxiety). CONCLUSIONS -: The current findings suggest that hopefulness may predict resilience after HCRC genetic testing in Hong Kong Chinese. Interventions to increase the level of hope may be beneficial to the psychological adjustment of CRC genetic testing recipients.",2010 Jun 11,"['Ho, Samuel MY', 'Ho, Judy WC', 'Bonanno, George A', 'Chu, Annie TW', 'Chan, Emily MS']",BMC Cancer,,,True
68aa709cc13d459268d903c0a505c56dda9bcc81,PMC,Avoidance behaviors and negative psychological responses in the general population in the initial stage of the H1N1 pandemic in Hong Kong,http://dx.doi.org/10.1186/1471-2334-10-139,PMC2891756,20509887,CC BY,"BACKGROUND: During the SARS pandemic in Hong Kong, panic and worry were prevalent in the community and the general public avoided staying in public areas. Such avoidance behaviors could greatly impact daily routines of the community and the local economy. This study examined the prevalence of the avoidance behaviors (i.e. avoiding going out, visiting crowded places and visiting hospitals) and negative psychological responses of the general population in Hong Kong at the initial stage of the H1N1 epidemic. METHODS: A sample of 999 respondents was recruited in a population-based survey. Using random telephone numbers, respondents completed a structured questionnaire by telephone interviews at the 'pre-community spread phase' of the H1N1 epidemic in Hong Kong. RESULTS: This study found that 76.5% of the respondents currently avoided going out or visiting crowded places or hospitals, whilst 15% felt much worried about contracting H1N1 and 6% showed signs of emotional distress. Females, older respondents, those having unconfirmed beliefs about modes of transmissions, and those feeling worried and emotionally distressed due to H1N1 outbreak were more likely than others to adopt some avoidance behaviors. Those who perceived high severity and susceptibility of getting H1N1 and doubted the adequacy of governmental preparedness were more likely than others to feel emotionally distressed. CONCLUSIONS: The prevalence of avoidance behaviors was very high. Cognitions, including unconfirmed beliefs about modes of transmission, perceived severity and susceptibility were associated with some of the avoidance behaviors and emotional distress variables. Public health education should therefore provide clear messages to rectify relevant perceptions.",2010 May 28,"['Lau, Joseph TF', 'Griffiths, Sian', 'Choi, Kai Chow', 'Tsui, Hi Yi']",BMC Infect Dis,,,True
2d78b0600b84cfd57e11ba249ee58c159fe517ae,PMC,"The relationship between antibody status to bovine corona virus and bovine respiratory syncytial virus and disease incidence, reproduction and herd characteristics in dairy herds",http://dx.doi.org/10.1186/1751-0147-52-37,PMC2891787,20525326,CC BY,"BACKGROUND: Bovine respiratory syncytial virus (BRSV) and bovine corona virus (BCV) affects cattle worldwide. Our objective was to evaluate the effects of these infections on general health and reproduction parameters measurable on herd level and to explore the association between antibody status and some herd characteristics. METHODS: We collected a pooled milk sample from five primiparous cows from 79 Swedish dairy herds in September 2006. The samples were analysed for immunoglobulin G antibodies to BCV and BRSV with indirect enzyme-linked immunosorbent assays. Herd level data from 1 September 2005 to 30 August 2006 were accessed retrospectively. The location of the herds was mapped using a geographical information system. RESULTS: Ten herds were antibody negative to both viruses and were compared with 69 herds positive to BCV or BRSV or both. Positive herds had a higher (P = 0.001) bulk tank milk somatic cell count (BMSCC) compared with negative herds. The medians for all other analyzed health and reproductive parameters were consistently in favour of the herds negative to both viruses although the differences were not statistically significant. A higher proportion (P = 0.01) of herds used professional technicians for artificial insemination, rather than farm personnel, amongst the 33 herds negative to BCV compared with the 46 positive herds. CONCLUSIONS: Our result shows that herds that were antibody positive to BCV and/or BRSV had a higher BMSCC compared with herds negative to BCV and BRSV. There was also tendency that negative herds had a better general herd health compared with positive. A higher proportion amongst the BCV negative herds used external technicians for AI instead of farm personnel, indicating that it is possible to avoid infection although having regular visits. Negative herds were located in close proximity to positive herds, indicating that local spread and airborne transmission between herds might not be of great importance and that herds can stay free from these infection transmission although virus is circulating in the area.",2010 Jun 4,"['Ohlson, Anna', 'Emanuelson, Ulf', 'Tråvén, Madeleine', 'Alenius, Stefan']",Acta Vet Scand,,,True
d92ab60000f93cb3e6e10a1055b77224c8e9bae5,PMC,Entry and Fusion of Emerging Paramyxoviruses,http://dx.doi.org/10.1371/journal.ppat.1000881,PMC2891828,20585631,CC BY,,2010 Jun 24,"Dutch, Rebecca Ellis",PLoS Pathog,,,True
9e4f6e2dd8f847c11cc774c7083aa426f42a530e,PMC,Detection of Plant DNA in the Bronchoalveolar Lavage of Patients with Ventilator-Associated Pneumonia,http://dx.doi.org/10.1371/journal.pone.0011298,PMC2891989,20585574,CC BY,"BACKGROUND: Hospital-acquired infections such as nosocomial pneumonia are a serious cause of mortality for hospitalized patients, especially for those admitted to intensive care units (ICUs). Despite the number of the studies reported to date, the causative agents of pneumonia are not completely known. Herein, we found by molecular technique that vegetable and tobacco DNA may be detected in the bronchoalveolar lavage from patients with ventilator-associated pneumonia (VAP). METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we studied bronchoalveolar lavage (BAL) from patients admitted to ICUs with ventilator-associated pneumonia. BAL fluids were assessed with molecular tests, culture and blood culture. We successfully identified plant DNA in six patients out of 106 (6%) with ventilator-associated pneumonia. Inhalation was confirmed in four cases and suspected in the other two cases. Inhalation was significantly frequent in patients with plant DNA (four out of six patients) than those without plant DNA (three out of 100 patients) (P<0.001). Nicotiana tabacum chloroplast DNA was identified in three patients who were smokers (cases 2, 3 and 6). Cucurbita pepo, Morus bombycis and Triticum aestivum DNA were identified in cases 1, 4 and 5 respectively. Twenty-three different bacterial species, two viruses and five fungal species were identified from among these six patients by using molecular and culture techniques. Several of the pathogenic microorganisms identified are reported to be food-borne or tobacco plant-associated pathogens. CONCLUSIONS/SIGNIFICANCE: Our study shows that plants DNA may be identified in the BAL fluid of pneumonia patients, especially when exploring aspiration pneumonia, but the significance of the presence of plant DNA and its role in the pathogenesis of pneumonia is unknown and remains to be investigated. However, the identification of these plants may be a potential marker of aspiration in patients with pneumonia.",2010 Jun 24,"['Bousbia, Sabri', 'Papazian, Laurent', 'La Scola, Bernard', 'Raoult, Didier']",PLoS One,,,True
1054ed358dfede6e22877513169bef30c491c363,PMC,Class II Transactivator (CIITA) Enhances Cytoplasmic Processing of HIV-1 Pr55Gag,http://dx.doi.org/10.1371/journal.pone.0011304,PMC2892040,20585587,CC BY,"BACKGROUND: The Pr55(gag) (Gag) polyprotein of HIV serves as a scaffold for virion assembly and is thus essential for progeny virion budding and maturation. Gag localizes to the plasma membrane (PM) and membranes of late endosomes, allowing for release of infectious virus directly from the cell membrane and/or upon exocytosis. The host factors involved in Gag trafficking to these sites are largely unknown. Upon activation, CD4+ T cells, the primary target of HIV infection, express the class II transcriptional activator (CIITA) and therefore the MHC class II isotype, HLA-DR. Similar to Gag, HLA-DR localizes to the PM and at the membranes of endosomes and specialized vesicular MHC class II compartments (MIICs). In HIV producer cells, transient HLA-DR expression induces intracellular Gag accumulation and impairs virus release. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. However, neither of these phenomena is due to recapitulation of the class II antigen presentation pathway or CIITA-mediated transcriptional activation of virus genes. Interestingly, we demonstrate that CIITA, apart from its transcriptional effects, acts cytoplasmically to enhance Pr160(gag-pol) (Gag-Pol) levels and thereby the viral protease and Gag processing, accounting for the increased infectivity of virions from CIITA-expressing cells. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that CIITA enhances HIV Gag processing, and provides the first evidence of a novel, post-transcriptional, cytoplasmic function for a well-known transactivator.",2010 Jun 24,"['Porter, Kristen A.', 'Kelley, Lauren N.', 'George, Annette', 'Harton, Jonathan A.', 'Duus, Karen M.']",PLoS One,,,True
63c9d5537c05b45dde4b7584c66a95e839b582ff,PMC,A duplex real-time RT-PCR assay for detecting H5N1 avian influenza virus and pandemic H1N1 influenza virus,http://dx.doi.org/10.1186/1743-422X-7-113,PMC2892456,20515509,CC BY,"A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009) influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID(50 )(50% tissue culture infective dose) for H5N1 and 0.2 TCID(50 )for the pandemic H1N1, which was the same as that of each single-target RT-PCR for pandemic H1N1 and even more sensitive for H5N1 with the same primers and probes. No cross reactivity of detecting other subtype influenza viruses or respiratory tract viruses was observed. Two hundred and thirty-six clinical specimens were tested by comparing with single real-time RT-PCR and result from the duplex assay was 100% consistent with the results of single real-time RT-PCR and sequence analysis.",2010 Jun 2,"['Kang, Xiao-ping', 'Jiang, Tao', 'Li, Yong-qiang', 'Lin, Fang', 'Liu, Hong', 'Chang, Guo-hui', 'Zhu, Qing-yu', 'Qin, E-de', 'Qin, Cheng-feng', 'Yang, Yin-hui']",Virol J,,,True
18910856b917289b6bb3cc2cef0f78ff82ad4b02,PMC,The Impact of Matching Vaccine Strains and Post-SARS Public Health Efforts on Reducing Influenza-Associated Mortality among the Elderly,http://dx.doi.org/10.1371/journal.pone.0011317,PMC2892467,20592764,CC BY,"Public health administrators do not have effective models to predict excess influenza-associated mortality and monitor viral changes associated with it. This study evaluated the effect of matching/mismatching vaccine strains, type/subtype pattern changes in Taiwan's influenza viruses, and the impact of post-SARS (severe acute respiratory syndrome) public health efforts on excess influenza-associated mortalities among the elderly. A negative binomial model was developed to estimate Taiwan's monthly influenza-associated mortality among the elderly. We calculated three winter and annual excess influenza-associated mortalities [pneumonia and influenza (P&I), respiratory and circulatory, and all-cause] from the 1999–2000 through the 2006–2007 influenza seasons. Obtaining influenza virus sequences from the months/years in which death from P&I was excessive, we investigated molecular variation in vaccine-mismatched influenza viruses by comparing hemagglutinin 1 (HA1) of the circulating and vaccine strains. We found that the higher the isolation rate of A (H3N2) and vaccine-mismatched influenza viruses, the greater the monthly P&I mortality. However, this significant positive association became negative for higher matching of A (H3N2) and public health efforts with post-SARS effect. Mean excess P&I mortality for winters was significantly higher before 2003 than after that year [mean ± S.D.: 1.44±1.35 vs. 0.35±1.13, p = 0.04]. Further analysis revealed that vaccine-matched circulating influenza A viruses were significantly associated with lower excess P&I mortality during post-SARS winters (i.e., 2005–2007) than during pre-SARS winters [0.03±0.06 vs. 1.57±1.27, p = 0.01]. Stratification of these vaccine-matching and post-SARS effect showed substantial trends toward lower elderly excess P&I mortalities in winters with either mismatching vaccines during the post-SARS period or matching vaccines during the pre-SARS period. Importantly, all three excess mortalities were at their highest in May, 2003, when inter-hospital nosocomial infections were peaking. Furthermore, vaccine-mismatched H3N2 viruses circulating in the years with high excess P&I mortality exhibited both a lower amino acid identity percentage of HA1 between vaccine and circulating strains and a higher numbers of variations at epitope B. Our model can help future decision makers to estimate excess P&I mortality effectively, select and test virus strains for antigenic variation, and evaluate public health strategy effectiveness.",2010 Jun 25,"['Chan, Ta-Chien', 'Hsiao, Chuhsing Kate', 'Lee, Chang-Chun', 'Chiang, Po-Huang', 'Kao, Chuan-Liang', 'Liu, Chung-Ming', 'King, Chwan-Chuen']",PLoS One,,,True
17a5e67e3855ae5fa7d1a711f3249b6813c28386,PMC,"Insulin Degrading Enzyme Induces a Conformational Change in Varicella-Zoster Virus gE, and Enhances Virus Infectivity and Stability",http://dx.doi.org/10.1371/journal.pone.0011327,PMC2892511,20593027,CC0,"Varicella-zoster virus (VZV) glycoprotein E (gE) is essential for virus infectivity and binds to a cellular receptor, insulin-degrading enzyme (IDE), through its unique amino terminal extracellular domain. Previous work has shown IDE plays an important role in VZV infection and virus cell-to-cell spread, which is the sole route for VZV spread in vitro. Here we report that a recombinant soluble IDE (rIDE) enhances VZV infectivity at an early step of infection associated with an increase in virus internalization, and increases cell-to-cell spread. VZV mutants lacking the IDE binding domain of gE were impaired for syncytia formation and membrane fusion. Pre-treatment of cell-free VZV with rIDE markedly enhanced the stability of the virus over a range of conditions. rIDE interacted with gE to elicit a conformational change in gE and rendered it more susceptible to proteolysis. Co-incubation of rIDE with gE modified the size of gE. We propose that the conformational change in gE elicited by IDE enhances infectivity and stability of the virus and leads to increased fusogenicity during VZV infection. The ability of rIDE to enhance infectivity of cell-free VZV over a wide range of incubation times and temperatures suggests that rIDE may be useful for increasing the stability of varicella or zoster vaccines.",2010 Jun 25,"['Li, Qingxue', 'Ali, Mir A.', 'Wang, Kening', 'Sayre, Dean', 'Hamel, Frederick G.', 'Fischer, Elizabeth R.', 'Bennett, Robert G.', 'Cohen, Jeffrey I.']",PLoS One,,,True
5f1378b1fa0165baf6bd31d9e4d0d66d818a37c6,PMC,Aerosol influenza transmission risk contours: A study of humid tropics versus winter temperate zone,http://dx.doi.org/10.1186/1743-422X-7-98,PMC2893155,20470403,CC BY,"BACKGROUND: In recent years, much attention has been given to the spread of influenza around the world. With the continuing human outbreak of H5N1 beginning in 2003 and the H1N1 pandemic in 2009, focus on influenza and other respiratory viruses has been increased. It has been accepted for decades that international travel via jet aircraft is a major vector for global spread of influenza, and epidemiological differences between tropical and temperate regions observed. Thus we wanted to study how indoor environmental conditions (enclosed locations) in the tropics and winter temperate zones contribute to the aerosol spread of influenza by travelers. To this end, a survey consisting of 632 readings of temperature (T) versus relative humidity (RH) in 389 different enclosed locations air travelers are likely to visit in 8 tropical nations were compared to 102 such readings in 2 Australian cities, including ground transport, hotels, shops, offices and other publicly accessible locations, along with 586 time course readings from aircraft. RESULTS: An influenza transmission risk contour map was developed for T versus RH. Empirical equations were created for estimating: 1. risk relative to temperature and RH, and 2. time parameterized influenza transmission risk. Using the transmission risk contours and equations, transmission risk for each country's locations was compared with influenza reports from the countries. Higher risk enclosed locations in the tropics included new automobile transport, luxury buses, luxury hotels, and bank branches. Most temperate locations were high risk. CONCLUSION: Environmental control is recommended for public health mitigation focused on higher risk enclosed locations. Public health can make use of the methods developed to track potential vulnerability to aerosol influenza. The methods presented can also be used in influenza modeling. Accounting for differential aerosol transmission using T and RH can potentially explain anomalies of influenza epidemiology in addition to seasonality in temperate climates.",2010 May 14,"['Hanley, Brian P', 'Borup, Birthe']",Virol J,,,True
c24060d084e314b214e061995b5528b2e0071e31,PMC,CXCR2 Signaling Protects Oligodendrocytes and Restricts Demyelination in a Mouse Model of Viral-Induced Demyelination,http://dx.doi.org/10.1371/journal.pone.0011340,PMC2893165,20596532,CC BY,"BACKGROUND: The functional role of ELR-positive CXC chemokines during viral – induced demyelination was assessed. Inoculation of the neuroattenuated JHM strain of mouse hepatitis virus (JHMV) into the CNS of susceptible mice results in an acute encephalomyelitis that evolves into a chronic demyelinating disease, modeling white matter pathology observed in the human demyelinating disease Multiple Sclerosis. METHODOLOGY/PRINCIPAL FINDINGS: JHMV infection induced the rapid and sustained expression of transcripts specific for the ELR (+) chemokine ligands CXCL1 and CXCL2, as well as their binding receptor CXCR2, which was enriched within the spinal cord during chronic infection. Inhibiting CXCR2 signaling with neutralizing antiserum significantly (p<0.03) delayed clinical recovery. Moreover, CXCR2 neutralization was associated with an increase in the severity of demyelination that was independent of viral recrudescence or modulation of neuroinflammation. Rather, blocking CXCR2 was associated with increased numbers of apoptotic cells primarily within white matter tracts, suggesting that oligodendrocytes were affected. JHMV infection of enriched oligodendrocyte progenitor cell (OPC) cultures revealed that apoptosis was associated with elevated expression of cleaved caspase 3 and muted Bcl-2 expression. Inclusion of CXCL1 within JHMV infected cultures restricted caspase 3 cleavage and increased Bcl-2 expression that was associated with a significant (p<0.001) decrease in apoptosis. CXCR2 deficient oligodendrocytes were refractory to CXCL1 mediated protection from JHMV – induced apoptosis, readily activating caspase 3 and down regulating Bcl-2. CONCLUSION/SIGNIFICANCE: These findings highlight a previously unappreciated role for CXCR2 signaling in protecting oligodendrocyte lineage cells from apoptosis during inflammatory demyelination initiated by viral infection of the CNS.",2010 Jun 28,"['Hosking, Martin P.', 'Tirotta, Emanuele', 'Ransohoff, Richard M.', 'Lane, Thomas E.']",PLoS One,,,True
8126e29c1a00af5300f325021430faf4dfecbdc0,PMC,Pandemic (H1N1) 2009 Influenza Community Transmission Was Established in One Australian State When the Virus Was First Identified in North America,http://dx.doi.org/10.1371/journal.pone.0011341,PMC2893203,20596536,CC BY,"BACKGROUND: In mid-June 2009 the State of Victoria in Australia appeared to have the highest notification rate of pandemic (H1N1) 2009 influenza in the world. We hypothesise that this was because community transmission of pandemic influenza was already well established in Victoria at the time testing for the novel virus commenced. In contrast, this was not true for the pandemic in other parts of Australia, including Western Australia (WA). METHODS: We used data from detailed case follow-up of patients with confirmed infection in Victoria and WA to demonstrate the difference in the pandemic curve in two Australian states on opposite sides of the continent. We modelled the pandemic in both states, using a susceptible-infected-removed model with Bayesian inference accounting for imported cases. RESULTS: Epidemic transmission occurred earlier in Victoria and later in WA. Only 5% of the first 100 Victorian cases were not locally acquired and three of these were brothers in one family. By contrast, 53% of the first 102 cases in WA were associated with importation from Victoria. Using plausible model input data, estimation of the effective reproductive number for the Victorian epidemic required us to invoke an earlier date for commencement of transmission to explain the observed data. This was not required in modelling the epidemic in WA. CONCLUSION: Strong circumstantial evidence, supported by modelling, suggests community transmission of pandemic influenza was well established in Victoria, but not in WA, at the time testing for the novel virus commenced in Australia. The virus is likely to have entered Victoria and already become established around the time it was first identified in the US and Mexico.",2010 Jun 28,"['Kelly, Heath A.', 'Mercer, Geoff N.', 'Fielding, James E.', 'Dowse, Gary K.', 'Glass, Kathryn', 'Carcione, Dale', 'Grant, Kristina A.', 'Effler, Paul V.', 'Lester, Rosemary A.']",PLoS One,,,True
4a326f7b32461745b6e168b454a214839b704865,PMC,A Clathrin Independent Macropinocytosis-Like Entry Mechanism Used by Bluetongue Virus-1 during Infection of BHK Cells,http://dx.doi.org/10.1371/journal.pone.0011360,PMC2894058,20613878,CC BY,"Acid dependent infection of Hela and Vero cells by BTV-10 occurs from within early-endosomes following virus uptake by clathrin-mediated endocytosis (Forzan et al., 2007: J Virol 81: 4819–4827). Here we report that BTV-1 infection of BHK cells is also dependent on a low endosomal pH; however, virus entry and infection were not inhibited by dominant-negative mutants of Eps15, AP180 or the ‘aa’ splice variant of dynamin-2, which were shown to inhibit clathrin-mediated endocytosis. In addition, infection was not inhibited by depletion of cellular cholesterol, which suggests that virus entry is not mediated by a lipid-raft dependent process such as caveolae-mediated endocytosis. Although virus entry and infection were not inhibited by the dominant-negative dynamin-2 mutant, entry was inhibited by the general dynamin inhibitor, dynasore, indicating that virus entry is dynamin dependent. During entry, BTV-1 co-localised with LAMP-1 but not with transferrin, suggesting that virus is delivered to late-endosomal compartments without first passing through early-endosomes. BTV-1 entry and infection were inhibited by EIPA and cytochalasin-D, known macropinocytosis inhibitors, and during entry virus co-localised with dextran, a known marker for macropinocytosis/fluid-phase uptake. Our results extend earlier observations with BTV-10, and show that BTV-1 can infect BHK cells via an entry mechanism that is clathrin and cholesterol-independent, but requires dynamin, and shares certain characteristics in common with macropinocytosis.",2010 Jun 29,"['Gold, Sarah', 'Monaghan, Paul', 'Mertens, Peter', 'Jackson, Terry']",PLoS One,,,True
eaccbbd4d93f295b6c22ae217f159c288b29deb6,PMC,Understanding PRRSV Infection in Porcine Lung Based on Genome-Wide Transcriptome Response Identified by Deep Sequencing,http://dx.doi.org/10.1371/journal.pone.0011377,PMC2894071,20614006,CC BY,"Porcine reproductive and respiratory syndrome (PRRS) has been one of the most economically important diseases affecting swine industry worldwide and causes great economic losses each year. PRRS virus (PRRSV) replicates mainly in porcine alveolar macrophages (PAMs) and dendritic cells (DCs) and develops persistent infections, antibody-dependent enhancement (ADE), interstitial pneumonia and immunosuppression. But the molecular mechanisms of PRRSV infection still are poorly understood. Here we report on the first genome-wide host transcriptional responses to classical North American type PRRSV (N-PRRSV) strain CH 1a infection using Solexa/Illumina's digital gene expression (DGE) system, a tag-based high-throughput transcriptome sequencing method, and analyse systematically the relationship between pulmonary gene expression profiles after N-PRRSV infection and infection pathology. Our results suggest that N-PRRSV appeared to utilize multiple strategies for its replication and spread in infected pigs, including subverting host innate immune response, inducing an anti-apoptotic and anti-inflammatory state as well as developing ADE. Upregulation expression of virus-induced pro-inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes and inflammatory cells, antibodies, complement activation were likely to result in the development of inflammatory responses during N-PRRSV infection processes. N-PRRSV-induced immunosuppression might be mediated by apoptosis of infected cells, which caused depletion of immune cells and induced an anti-inflammatory cytokine response in which they were unable to eradicate the primary infection. Our systems analysis will benefit for better understanding the molecular pathogenesis of N-PRRSV infection, developing novel antiviral therapies and identifying genetic components for swine resistance/susceptibility to PRRS.",2010 Jun 29,"['Xiao, Shuqi', 'Jia, Jianyu', 'Mo, Delin', 'Wang, Qiwei', 'Qin, Limei', 'He, Zuyong', 'Zhao, Xiao', 'Huang, Yuankai', 'Li, Anning', 'Yu, Jingwei', 'Niu, Yuna', 'Liu, Xiaohong', 'Chen, Yaosheng']",PLoS One,,,True
3e339ee119ba0065cad4c40897cd1bc9dd0f118a,PMC,Interactions of SARS Coronavirus Nucleocapsid Protein with the host cell proteasome subunit p42,http://dx.doi.org/10.1186/1743-422X-7-99,PMC2894783,20478047,CC BY,"BACKGROUND: Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spreads rapidly and has a high case-mortality rate. The nucleocapsid protein (NP) of SARS-CoV may be critical for pathogenicity. This study sought to discover the host proteins that interact with SARS-CoV NP. RESULTS: Using surface plasmon resonance biomolecular interaction analysis (SPR/BIA) and matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry, we found that only the proteasome subunit p42 from human fetal lung diploid fibroblast (2BS) cells bound to SARS-CoV NP. This interaction was confirmed by the glutathione S-transferase (GST) fusion protein pulldown technique. The co-localization signal of SARS-CoV NP and proteasome subunit p42 in 2BS cells was detected using indirect immunofluorescence and confocal microscopy. p42 is a subunit of the 26S proteasome; this large, multi-protein complex is a component of the ubiquitin-proteasome pathway, which is involved in a variety of basic cellular processes and inflammatory responses. CONCLUSION: To our knowledge, this is the first report that SARS-CoV NP interacts with the proteasome subunit p42 within host cells. These data enhance our understanding of the molecular mechanisms of SARS-CoV pathogenicity and the means by which SARS-CoV interacts with host cells.",2010 May 17,"['Wang, Qin', 'Li, Chuan', 'Zhang, Quanfu', 'Wang, Tao', 'Li, Jiandong', 'Guan, Wuxiang', 'Yu, Jianshi', 'Liang, Mifang', 'Li, Dexin']",Virol J,,,True
f5133d66a71eb5add9881ec5f254fc0757a7ee06,PMC,A dynamic estimation of the daily cumulative cases during infectious disease surveillance: application to dengue fever,http://dx.doi.org/10.1186/1471-2334-10-136,PMC2894833,20504379,CC BY,"BACKGROUND: In infectious disease surveillance, when the laboratory confirmation of the cases is time-consuming, there is often a time lag between the number of suspect cases and the number of confirmed cases. This study proposes a dynamic statistical model to estimate the daily number of new cases and the daily cumulative number of infected cases, which was then applied to historic dengue fever data. METHODS: The duration between the date of disease onset and date of laboratory confirmation was assumed to follow a gamma distribution or a nonparametric distribution. A conditional probability of a case being a real case among the unconfirmed cases on a given date was then calculated. This probability along with the observed confirmed cases was integrated to estimate the daily number of new cases and the cumulative number of infected cases. RESULTS: The distribution of the onset-to-confirmation time for the positive cases was different from that of the negative cases. The daily new cases and cumulative epidemic curves estimated by the proposed method have a lower absolute relative bias than the values estimated solely based on the available daily-confirmed cases. CONCLUSION: The proposed method provides a more accurate real-time estimation of the daily new cases and daily cumulative number of infected cases. The model makes use of the most recent ""moving window"" of information relative to suspect cases and dynamically updates the parameters. The proposed method will be useful for the real-time evaluation of a disease outbreak when case classification requires a time-consuming laboratory process to identify a confirmed case.",2010 May 27,"['Chuang, Pei-Hung', 'Chuang, Jen-Hsiang', 'Lin, I-Feng']",BMC Infect Dis,,,True
bc7b2271acba0248f021e9e11cb91cec6358d924,PMC,Assessing the human immune system through blood transcriptomics,http://dx.doi.org/10.1186/1741-7007-8-84,PMC2895587,20619006,CC BY,Blood is the pipeline of the immune system. Assessing changes in transcript abundance in blood on a genome-wide scale affords a comprehensive view of the status of the immune system in health and disease. This review summarizes the work that has used this approach to identify therapeutic targets and biomarker signatures in the field of autoimmunity and infectious disease. Recent technological and methodological advances that will carry the blood transcriptome research field forward are also discussed.,2010 Jul 1,"['Chaussabel, Damien', 'Pascual, Virginia', 'Banchereau, Jacques']",BMC Biol,,,True
b5e924927b31aface620ada453f904e6e9ebb203,PMC,Bid Regulates the Pathogenesis of Neurotropic Reovirus,http://dx.doi.org/10.1371/journal.ppat.1000980,PMC2895667,20617182,CC BY,"Reovirus infection leads to apoptosis in both cultured cells and the murine central nervous system (CNS). NF-κB-driven transcription of proapoptotic cellular genes is required for the effector phase of the apoptotic response. Although both extrinsic death-receptor signaling pathways and intrinsic pathways involving mitochondrial injury are implicated in reovirus-induced apoptosis, mechanisms by which either of these pathways are activated and their relationship to NF-κB signaling following reovirus infection are unknown. The proapoptotic Bcl-2 family member, Bid, is activated by proteolytic cleavage following reovirus infection. To understand how reovirus integrates host signaling circuits to induce apoptosis, we examined proapoptotic signaling following infection of Bid-deficient cells. Although reovirus growth was not affected by the absence of Bid, cells lacking Bid failed to undergo apoptosis. Furthermore, we found that NF-κB activation is required for Bid cleavage and subsequent proapoptotic signaling. To examine the functional significance of Bid-dependent apoptosis in reovirus disease, we monitored fatal encephalitis caused by reovirus in the presence and absence of Bid. Survival of Bid-deficient mice was significantly enhanced in comparison to wild-type mice following either peroral or intracranial inoculation of reovirus. Decreased reovirus virulence in Bid-null mice was accompanied by a reduction in viral yield. These findings define a role for NF-κB-dependent cleavage of Bid in the cell death program initiated by viral infection and link Bid to viral virulence.",2010 Jul 1,"['Danthi, Pranav', 'Pruijssers, Andrea J.', 'Berger, Angela K.', 'Holm, Geoffrey H.', 'Zinkel, Sandra S.', 'Dermody, Terence S.']",PLoS Pathog,,,True
30fc9806c9b1ba0d786a31cad4a1d98b6642462d,PMC,Pandemic influenza preparedness and health systems challenges in Asia: results from rapid analyses in 6 Asian countries,http://dx.doi.org/10.1186/1471-2458-10-322,PMC2896940,20529345,CC BY,"BACKGROUND: Since 2003, Asia-Pacific, particularly Southeast Asia, has received substantial attention because of the anticipation that it could be the epicentre of the next pandemic. There has been active investment but earlier review of pandemic preparedness plans in the region reveals that the translation of these strategic plans into operational plans is still lacking in some countries particularly those with low resources. The objective of this study is to understand the pandemic preparedness programmes, the health systems context, and challenges and constraints specific to the six Asian countries namely Cambodia, Indonesia, Lao PDR, Taiwan, Thailand, and Viet Nam in the prepandemic phase before the start of H1N1/2009. METHODS: The study relied on the Systemic Rapid Assessment (SYSRA) toolkit, which evaluates priority disease programmes by taking into account the programmes, the general health system, and the wider socio-cultural and political context. The components under review were: external context; stewardship and organisational arrangements; financing, resource generation and allocation; healthcare provision; and information systems. Qualitative and quantitative data were collected in the second half of 2008 based on a review of published data and interviews with key informants, exploring past and current patterns of health programme and pandemic response. RESULTS: The study shows that health systems in the six countries varied in regard to the epidemiological context, health care financing, and health service provision patterns. For pandemic preparation, all six countries have developed national governance on pandemic preparedness as well as national pandemic influenza preparedness plans and Avian and Human Influenza (AHI) response plans. However, the governance arrangements and the nature of the plans differed. In the five developing countries, the focus was on surveillance and rapid containment of poultry related transmission while preparation for later pandemic stages was limited. The interfaces and linkages between health system contexts and pandemic preparedness programmes in these countries were explored. CONCLUSION: Health system context influences how the six countries have been preparing themselves for a pandemic. At the same time, investment in pandemic preparation in the six Asian countries has contributed to improvement in health system surveillance, laboratory capacity, monitoring and evaluation and public communications. A number of suggestions for improvement were presented to strengthen the pandemic preparation and mitigation as well as to overcome some of the underlying health system constraints.",2010 Jun 8,"['Hanvoravongchai, Piya', 'Adisasmito, Wiku', 'Chau, Pham Ngoc', 'Conseil, Alexandra', 'de Sa, Joia', 'Krumkamp, Ralf', 'Mounier-Jack, Sandra', 'Phommasack, Bounlay', 'Putthasri, Weerasak', 'Shih, Chin-Shui', 'Touch, Sok', 'Coker, Richard']",BMC Public Health,,,True
876ae65a682f1bf2941f54851442532ae722382c,PMC,Whole-proteome phylogeny of large dsDNA viruses and parvoviruses through a composition vector method related to dynamical language model,http://dx.doi.org/10.1186/1471-2148-10-192,PMC2898692,20565983,CC BY,"BACKGROUND: The vast sequence divergence among different virus groups has presented a great challenge to alignment-based analysis of virus phylogeny. Due to the problems caused by the uncertainty in alignment, existing tools for phylogenetic analysis based on multiple alignment could not be directly applied to the whole-genome comparison and phylogenomic studies of viruses. There has been a growing interest in alignment-free methods for phylogenetic analysis using complete genome data. Among the alignment-free methods, a dynamical language (DL) method proposed by our group has successfully been applied to the phylogenetic analysis of bacteria and chloroplast genomes. RESULTS: In this paper, the DL method is used to analyze the whole-proteome phylogeny of 124 large dsDNA viruses and 30 parvoviruses, two data sets with large difference in genome size. The trees from our analyses are in good agreement to the latest classification of large dsDNA viruses and parvoviruses by the International Committee on Taxonomy of Viruses (ICTV). CONCLUSIONS: The present method provides a new way for recovering the phylogeny of large dsDNA viruses and parvoviruses, and also some insights on the affiliation of a number of unclassified viruses. In comparison, some alignment-free methods such as the CV Tree method can be used for recovering the phylogeny of large dsDNA viruses, but they are not suitable for resolving the phylogeny of parvoviruses with a much smaller genome size.",2010 Jun 22,"['Yu, Zu-Guo', 'Chu, Ka Hou', 'Li, Chi Pang', 'Anh, Vo', 'Zhou, Li-Qian', 'Wang, Roger Wei']",BMC Evol Biol,,,True
9940375ae218bef442080efc4b430cf27323a4a6,PMC,Co-lethality studied as an asset against viral drug escape: the HIV protease case,http://dx.doi.org/10.1186/1745-6150-5-40,PMC2898770,20565756,CC BY,"BACKGROUND: Co-lethality, or synthetic lethality is the documented genetic situation where two, separately non-lethal mutations, become lethal when combined in one genome. Each mutation is called a ""synthetic lethal"" (SL) or a co-lethal. Like invariant positions, SL sets (SL linked couples) are choice targets for drug design against fast-escaping RNA viruses: mutational viral escape by loss of affinity to the drug may induce (synthetic) lethality. RESULTS: From an amino acid sequence alignment of the HIV protease, we detected the potential SL couples, potential SL sets, and invariant positions. From the 3D structure of the same protein we focused on the ones that were close to each other and accessible on the protein surface, to possibly bind putative drugs. We aligned 24,155 HIV protease amino acid sequences and identified 290 potential SL couples and 25 invariant positions. After applying the distance and accessibility filter, three candidate drug design targets of respectively 7 (under the flap), 4 (in the cantilever) and 5 (in the fulcrum) amino acid positions were found. CONCLUSIONS: These three replication-critical targets, located outside of the active site, are key to our anti-escape strategy. Indeed, biological evidence shows that 2/3 of those target positions perform essential biological functions. Their mutational variations to escape antiviral medication could be lethal, thus limiting the apparition of drug-resistant strains. REVIEWERS: This article was reviewed by Arcady Mushegian, Shamil Sunyaev and Claus Wilke.",2010 Jun 17,"['Brouillet, Sophie', 'Valere, Thomas', 'Ollivier, Emmanuelle', 'Marsan, Laurent', 'Vanet, Anne']",Biol Direct,,,True
31f9d7bce1db40d866a3e93b06ff9515c34fc3b7,PMC,Spatial patterns of Bovine Corona Virus and Bovine Respiratory Syncytial Virus in the Swedish beef cattle population,http://dx.doi.org/10.1186/1751-0147-52-33,PMC2898781,20492637,CC BY,"BACKGROUND: Both bovine coronavirus (BCV) and bovine respiratory syncytial virus (BRSV) infections are currently wide-spread in the Swedish dairy cattle population. Surveys of antibody levels in bulk tank milk have shown very high nationwide prevalences of both BCV and BRSV, with large variations between regions. In the Swedish beef cattle population however, no investigations have yet been performed regarding the prevalence and geographical distribution of BCV and BRSV. A cross-sectional serological survey for BCV and BRSV was carried out in Swedish beef cattle to explore any geographical patterns of these infections. METHODS: Blood samples were collected from 2,763 animals located in 2,137 herds and analyzed for presence of antibodies to BCV and BRSV. Moran's I was calculated to assess spatial autocorrelation, and identification of geographical cluster was performed using spatial scan statistics. RESULTS: Animals detected positive to BCV or BRSV were predominately located in the central-western and some southern parts of Sweden. Moran's I indicated global spatial autocorrelation. BCV and BRSV appeared to be spatially related: two areas in southern Sweden (Skaraborg and Skåne) had a significantly higher prevalence of BCV (72.5 and 65.5% respectively); almost the same two areas were identified as being high-prevalence clusters for BRSV (69.2 and 66.8% respectively). An area in south-east Sweden (Kronoberg-Blekinge) had lower prevalences for both infections than expected (23.8 and 20.7% for BCV and BRSV respectively). Another area in middle-west Sweden (Värmland-Dalarna) had also a lower prevalence for BRSV (7.9%). Areas with beef herd density > 10 per 100 km(2 )were found to be at significantly higher risk of being part of high-prevalence clusters. CONCLUSION: These results form a basis for further investigations of between-herds dynamics and risk factors for these infections in order to design effective control strategies.",2010 May 21,"['Beaudeau, Francois', 'Björkman, Camilla', 'Alenius, Stefan', 'Frössling, Jenny']",Acta Vet Scand,,,True
2183478af3f9343c0f566eee8b5d95a1abea6754,PMC,The First Human Epitope Map of the Alphaviral E1 and E2 Proteins Reveals a New E2 Epitope with Significant Virus Neutralizing Activity,http://dx.doi.org/10.1371/journal.pntd.0000739,PMC2903468,20644615,CC0,"BACKGROUND: Venezuelan equine encephalitis virus (VEEV) is responsible for VEE epidemics that occur in South and Central America and the U.S. The VEEV envelope contains two glycoproteins E1 (mediates cell membrane fusion) and E2 (binds receptor and elicits virus neutralizing antibodies). Previously we constructed E1 and E2 epitope maps using murine monoclonal antibodies (mMAbs). Six E2 epitopes (E2(c,d,e,f,g,h)) bound VEEV-neutralizing antibody and mapped to amino acids (aa) 182–207. Nothing is known about the human antibody repertoire to VEEV or epitopes that engage human virus-neutralizing antibodies. There is no specific treatment for VEE; however virus-neutralizing mMAbs are potent protective and therapeutic agents for mice challenged with VEEV by either peripheral or aerosol routes. Therefore, fully human MAbs (hMAbs) with virus-neutralizing activity should be useful for prevention or clinical treatment of human VEE. METHODS: We used phage-display to isolate VEEV-specific hFabs from human bone marrow donors. These hFabs were characterized by sequencing, specificity testing, VEEV subtype cross-reactivity using indirect ELISA, and in vitro virus neutralization capacity. One E2-specific neutralizing hFAb, F5n, was converted into IgG, and its binding site was identified using competitive ELISA with mMAbs and by preparing and sequencing antibody neutralization-escape variants. FINDINGS: Using 11 VEEV-reactive hFabs we constructed the first human epitope map for the alphaviral surface proteins E1 and E2. We identified an important neutralization-associated epitope unique to the human immune response, E2 aa115–119. Using a 9 Å resolution cryo-electron microscopy map of the Sindbis virus E2 protein, we showed the probable surface location of this human VEEV epitope. CONCLUSIONS: The VEEV-neutralizing capacity of the hMAb F5 nIgG is similar to that exhibited by the humanized mMAb Hy4 IgG. The Hy4 IgG has been shown to limit VEEV infection in mice both prophylactically and therapeutically. Administration of a cocktail of F5n and Hy4 IgGs, which bind to different E2 epitopes, could provide enhanced prophylaxis or immunotherapy for VEEV, while reducing the possibility of generating possibly harmful virus neutralization-escape variants in vivo.",2010 Jul 13,"['Hunt, Ann R.', 'Frederickson, Shana', 'Maruyama, Toshiaki', 'Roehrig, John T.', 'Blair, Carol D.']",PLoS Negl Trop Dis,,,True
b29aec7c51b6c428e566fa6e092797fc4da21b29,PMC,The Battle between Virus and Host: Modulation of Toll-Like Receptor Signaling Pathways by Virus Infection,http://dx.doi.org/10.1155/2010/184328,PMC2903949,20672047,CC BY,"In order to establish an infection, viruses need to either suppress or escape from host immune defense systems. Recent immunological research has focused on innate immunity as the first line of host defense, especially pattern recognition molecules such as Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and NOD-like receptors (NLRs). Various microbial components are recognized by their vague and common molecular shapes so-called, pathogen-associated molecular patterns (PAMPs). PAMPs induce inflammatory reactions mediated by the activation of the transcription factor, NF-κB, and by interferons, which lead to an antiviral immune response. Viruses have the capacity to suppress or escape from this pattern recognition molecule-mediated antimicrobial response in various ways. In this paper, we review the various strategies used by viruses to modulate the pattern recognition molecule-mediated innate immune response.",2010 Jun 16,"['Yokota, Shin-ichi', 'Okabayashi, Tamaki', 'Fujii, Nobuhiro']",Mediators Inflamm,,,True
6af49373c566eac05d2609e3474e847157cafb3b,PMC,Proteomic analysis of primary duck hepatocytes infected with duck hepatitis B virus,http://dx.doi.org/10.1186/1477-5956-8-28,PMC2904733,20529248,CC BY,"BACKGROUND: Hepatitis B virus (HBV) is a major cause of liver infection in human. Because of the lack of an appropriate cell culture system for supporting HBV infection efficiently, the cellular and molecular mechanisms of hepadnavirus infection remain incompletely understood. Duck heptatitis B virus (DHBV) can naturally infect primary duck hepatocytes (PDHs) that provide valuable model systems for studying hepadnavirus infection in vitro. In this report, we explored global changes in cellular protein expression in DHBV infected PDHs by two-dimension gel electrophoresis (2-DE) combined with MALDI-TOF/TOF tandem mass spectrometry (MS/MS). RESULTS: The effects of hepadnavirus infection on hepatocytes were investigated in DHBV infected PDHs by the 2-DE analysis. Proteomic profile of PDHs infected with DHBV were analyzed at 24, 72 and 120 h post-infection by comparing with uninfected PDHs, and 75 differentially expressed protein spots were revealed by 2-DE analysis. Among the selected protein spots, 51 spots were identified corresponding to 42 proteins by MS/MS analysis; most of them were matched to orthologous proteins of Gallus gallus, Anas platyrhynchos or other avian species, including alpha-enolase, lamin A, aconitase 2, cofilin-2 and annexin A2, etc. The down-regulated expression of beta-actin and annexin A2 was confirmed by Western blot analysis, and potential roles of some differentially expressed proteins in the virus-infected cells have been discussed. CONCLUSIONS: Differentially expressed proteins of DHBV infected PDHs revealed by 2-DE, are involved in carbohydrate metabolism, amino acid metabolism, stress responses and cytoskeleton processes etc, providing the insight to understanding of interactions between hepadnavirus and hepatocytes and molecular mechanisms of hepadnavirus pathogenesis.",2010 Jun 7,"['Zhao, Yanfeng', 'Ben, Haijing', 'Qu, Su', 'Zhou, Xinwen', 'Yan, Liang', 'Xu, Bin', 'Zhou, Shuangcheng', 'Lou, Qiang', 'Ye, Rong', 'Zhou, Tianlun', 'Yang, Pengyuan', 'Qu, Di']",Proteome Sci,,,True
7ce8b2a6ee1373cf063fa46c1cdc81151babc7e1,PMC,The identification of unique serum proteins of HIV-1 latently infected long-term non-progressor patients,http://dx.doi.org/10.1186/1742-6405-7-21,PMC2908552,20604950,CC BY,"BACKGROUND: The search for disease biomarkers within human peripheral fluids has become a favorable approach to preventative therapeutics throughout the past few years. The comparison of normal versus disease states can identify an overexpression or a suppression of critical proteins where illness has directly altered a patient's cellular homeostasis. In particular, the analysis of HIV-1 infected serum is an attractive medium with which to identify altered protein expression due to the ease and non-invasive methods of collecting samples as well as the corresponding insight into the in vivo interaction of the virus with infected cells/tissue. The utilization of proteomic techniques to globally identify differentially expressed serum proteins in response to HIV-1 infection is a significant undertaking that is complicated due to the innate protein profile of human serum. RESULTS: Here, the depletion of 12 of the most abundant serum proteins, followed by two-dimensional gel electrophoresis coupled with identification of these proteins using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, has allowed for the identification of differentially expressed, low abundant serum proteins. We have analyzed and compared serum samples from HIV-1 infected subjects who are being treated using highly active antiretroviral therapy (HAART) to those who are latently infected but have not progressed to AIDS despite the absence of treatment, i.e. long term non-progressors (LTNPs). Here we have identified unique serum proteins that are differentially expressed in LTNP HIV-1 patients and may contribute to the ability of these patients to combat HIV-1 infection in the absence of HAART. We focused on the cdk4/6 cell cycle inhibitor p16(INK4A )and found that the treatment of HIV-1 latently infected cell lines with p16(INK4A )decreases viral production despite it not being expressed endogenously in these cells. CONCLUSIONS: Identification of these unique proteins may serve as an indication of altered viral states in response to infection as well as a natural phenotypic variability in response to HIV-1 infection in a given population.",2010 Jul 6,"['Van Duyne, Rachel', 'Guendel, Irene', 'Kehn-Hall, Kylene', 'Easley, Rebecca', 'Klase, Zachary', 'Liu, Chenglong', 'Young, Mary', 'Kashanchi, Fatah']",AIDS Res Ther,,,True
00cf719db65d07c0c7bdea9defaea448fc5f5786,PMC,A Systems Immunology Approach to Plasmacytoid Dendritic Cell Function in Cytopathic Virus Infections,http://dx.doi.org/10.1371/journal.ppat.1001017,PMC2908624,20661432,CC BY,"Plasmacytoid dendritic cell (pDC)-mediated protection against cytopathic virus infection involves various molecular, cellular, tissue-scale, and organism-scale events. In order to better understand such multiscale interactions, we have implemented a systems immunology approach focusing on the analysis of the structure, dynamics and operating principles of virus-host interactions which constrain the initial spread of the pathogen. Using high-resolution experimental data sets coming from the well-described mouse hepatitis virus (MHV) model, we first calibrated basic modules including MHV infection of its primary target cells, i.e. pDCs and macrophages (Mφs). These basic building blocks were used to generate and validate an integrative mathematical model for in vivo infection dynamics. Parameter estimation for the system indicated that on a per capita basis, one infected pDC secretes sufficient type I IFN to protect 10(3) to 10(4) Mφs from cytopathic viral infection. This extremely high protective capacity of pDCs secures the spleen's capability to function as a ‘sink’ for the virus produced in peripheral organs such as the liver. Furthermore, our results suggest that the pDC population in spleen ensures a robust protection against virus variants which substantially down-modulate IFN secretion. However, the ability of pDCs to protect against severe disease caused by virus variants exhibiting an enhanced liver tropism and higher replication rates appears to be rather limited. Taken together, this systems immunology analysis suggests that antiviral therapy against cytopathic viruses should primarily limit viral replication within peripheral target organs.",2010 Jul 22,"['Bocharov, Gennady', 'Züst, Roland', 'Cervantes-Barragan, Luisa', 'Luzyanina, Tatyana', 'Chiglintsev, Egor', 'Chereshnev, Valery A.', 'Thiel, Volker', 'Ludewig, Burkhard']",PLoS Pathog,,,True
448c6dce11a897a8baa0815f46a77307b16049db,PMC,Nonparametric methods for the analysis of single-color pathogen microarrays,http://dx.doi.org/10.1186/1471-2105-11-354,PMC2909221,20584331,CC BY,"BACKGROUND: The analysis of oligonucleotide microarray data in pathogen surveillance and discovery is a challenging task. Target template concentration, nucleic acid integrity, and host nucleic acid composition can each have a profound effect on signal distribution. Exploratory analysis of fluorescent signal distribution in clinical samples has revealed deviations from normality, suggesting that distribution-free approaches should be applied. RESULTS: Positive predictive value and false positive rates were examined to assess the utility of three well-established nonparametric methods for the analysis of viral array hybridization data: (1) Mann-Whitney U, (2) the Spearman correlation coefficient and (3) the chi-square test. Of the three tests, the chi-square proved most useful. CONCLUSIONS: The acceptance of microarray use for routine clinical diagnostics will require that the technology be accompanied by simple yet reliable analytic methods. We report that our implementation of the chi-square test yielded a combination of low false positive rates and a high degree of predictive accuracy.",2010 Jun 28,"['Jabado, Omar J', 'Conlan, Sean', 'Quan, Phenix-Lan', 'Hui, Jeffrey', 'Palacios, Gustavo', 'Hornig, Mady', 'Briese, Thomas', 'Lipkin, W Ian']",BMC Bioinformatics,,,True
99a643136f67ee7f56c5abdea714a2a2ca89c10e,PMC,"Pneumonia Incidence and Mortality in Mainland China: Systematic Review of Chinese and English Literature, 1985–2008",http://dx.doi.org/10.1371/journal.pone.0011721,PMC2909231,20668535,CC0,"BACKGROUND: Pneumonia is a leading infectious disease killer worldwide, yet the burden in China is not well understood as much of the data is published in the non-English literature. METHODOLOGY/PRINCIPAL FINDINGS: We systematically reviewed the Chinese- and English-language literature for studies with primary data on pneumonia incidence and mortality in mainland China. Between 1985 and 2008, 37 studies met the inclusion criteria. The quality of the studies was highly variable. For children <5 years, incidence ranged from 0.06–0.27 episodes per person-year and mortality ranged from 184–1,223 deaths per 100,000 population. Overall incidence and mortality were stable or decreased over the study period and were higher in rural compared to urban areas. CONCLUSIONS/SIGNIFICANCE: Pneumonia continues to be a major public health challenge in young children in China, and estimates of pneumonia incidence and mortality vary widely. Reliable surveillance data and new prevention efforts may be needed to achieve and document additional declines, especially in areas with higher incidence and mortality such as rural settings.",2010 Jul 23,"['Guan, Xuhua', 'Silk, Benjamin J.', 'Li, Wenkai', 'Fleischauer, Aaron T.', 'Xing, Xuesen', 'Jiang, Xiaoqing', 'Yu, Hongjie', 'Olsen, Sonja J.', 'Cohen, Adam L.']",PLoS One,,,True
a3778f543ef74ff3a0dd90250221b77ee38d7533,PMC,Inverse folding of RNA pseudoknot structures,http://dx.doi.org/10.1186/1748-7188-5-27,PMC2909241,20573197,CC BY,"BACKGROUND: RNA exhibits a variety of structural configurations. Here we consider a structure to be tantamount to the noncrossing Watson-Crick and G-U-base pairings (secondary structure) and additional cross-serial base pairs. These interactions are called pseudoknots and are observed across the whole spectrum of RNA functionalities. In the context of studying natural RNA structures, searching for new ribozymes and designing artificial RNA, it is of interest to find RNA sequences folding into a specific structure and to analyze their induced neutral networks. Since the established inverse folding algorithms, RNAinverse, RNA-SSD as well as INFO-RNA are limited to RNA secondary structures, we present in this paper the inverse folding algorithm Inv which can deal with 3-noncrossing, canonical pseudoknot structures. RESULTS: In this paper we present the inverse folding algorithm Inv. We give a detailed analysis of Inv, including pseudocodes. We show that Inv allows to design in particular 3-noncrossing nonplanar RNA pseudoknot 3-noncrossing RNA structures-a class which is difficult to construct via dynamic programming routines. Inv is freely available at http://www.combinatorics.cn/cbpc/inv.html. CONCLUSIONS: The algorithm Inv extends inverse folding capabilities to RNA pseudoknot structures. In comparison with RNAinverse it uses new ideas, for instance by considering sets of competing structures. As a result, Inv is not only able to find novel sequences even for RNA secondary structures, it does so in the context of competing structures that potentially exhibit cross-serial interactions.",2010 Jun 23,"['Gao, James ZM', 'Li, Linda YM', 'Reidys, Christian M']",Algorithms Mol Biol,,,True
8d1543ffb6bf876bc0a8fb927068f6f3c6938497,PMC,Proteomic analysis of purified coronavirus infectious bronchitis virus particles,http://dx.doi.org/10.1186/1477-5956-8-29,PMC2909931,20534109,CC BY,"BACKGROUND: Infectious bronchitis virus (IBV) is the coronavirus of domestic chickens causing major economic losses to the poultry industry. Because of the complexity of the IBV life cycle and the small number of viral structural proteins, important virus-host relationships likely remain to be discovered. Toward this goal, we performed two-dimensional gel electrophoresis fractionation coupled to mass spectrometry identification approaches to perform a comprehensive proteomic analysis of purified IBV particles. RESULTS: Apart from the virus-encoded structural proteins, we detected 60 host proteins in the purified virions which can be grouped into several functional categories including intracellular trafficking proteins (20%), molecular chaperone (18%), macromolcular biosynthesis proteins (17%), cytoskeletal proteins (15%), signal transport proteins (15%), protein degradation (8%), chromosome associated proteins (2%), ribosomal proteins (2%), and other function proteins (3%). Interestingly, 21 of the total host proteins have not been reported to be present in virions of other virus families, such as major vault protein, TENP protein, ovalbumin, and scavenger receptor protein. Following identification of the host proteins by proteomic methods, the presence of 4 proteins in the purified IBV preparation was verified by western blotting and immunogold labeling detection. CONCLUSIONS: The results present the first standard proteomic profile of IBV and may facilitate the understanding of the pathogenic mechanisms.",2010 Jun 9,"['Kong, Qingming', 'Xue, Chunyi', 'Ren, Xiangpeng', 'Zhang, Chengwen', 'Li, Linlin', 'Shu, Dingming', 'Bi, Yingzuo', 'Cao, Yongchang']",Proteome Sci,,,True
964442dc964b2d97ceef1883ce2353e866efd8c2,PMC,Difference of clinical features in childhood Mycoplasma pneumoniae pneumonia,http://dx.doi.org/10.1186/1471-2431-10-48,PMC2910686,20604923,CC BY,"BACKGROUND: M. pneumoniae pneumonia (MP) has been reported in 10-40% of community-acquired pneumonia cases. We aimed to evaluate the difference of clinical features in children with MP, according to their age and chest radiographic patterns. METHODS: The diagnosis of MP was made by examinations at both admission and discharge and by two serologic tests: the indirect microparticle agglutinin assay (≥1:40) and the cold agglutinins titer (≥1:32). A total of 191 children with MP were grouped by age: ≤2 years of age (29 patients), 3-5 years of age (81 patients), and ≥6 years of age (81 patients). They were also grouped by pneumonia pattern: bronchopneumonia group (96 patients) and segmental/lobar pneumonia group (95 patients). RESULTS: Eighty-six patients (45%) were seroconverters, and the others showed increased antibody titers during hospitalization. Among the three age groups, the oldest children showed the longest duration of fever, highest C-reactive protein (CRP) values, and the most severe pneumonia pattern. The patients with segmental/lobar pneumonia were older and had longer fever duration and lower white blood cell (WBC) and lymphocyte counts, compared with those with bronchopneumonia. The patient group with the most severe pulmonary lesions had the most prolonged fever, highest CRP, highest rate of seroconverters, and lowest lymphocyte counts. Thrombocytosis was observed in 8% of patients at admission, but in 33% of patients at discharge. CONCLUSIONS: In MP, older children had more prolonged fever and more severe pulmonary lesions. The severity of pulmonary lesions was associated with the absence of diagnostic IgM antibodies at presentation and lymphocyte count. Short-term paired IgM serologic test may be mandatory for early and definitive diagnosis of MP.",2010 Jul 6,"['Youn, You-Sook', 'Lee, Kyung-Yil', 'Hwang, Ja-Young', 'Rhim, Jung-Woo', 'Kang, Jin-Han', 'Lee, Joon-Sung', 'Kim, Ji-Chang']",BMC Pediatr,,,True
fac2afdb0450de6c766a24baf26e3ce6e03e09e2,PMC,HIV Antigen Incorporation within Adenovirus Hexon Hypervariable 2 for a Novel HIV Vaccine Approach,http://dx.doi.org/10.1371/journal.pone.0011815,PMC2910733,20676400,CC BY,"Adenoviral (Ad) vectors have been used for a variety of vaccine applications including cancer and infectious diseases. Traditionally, Ad-based vaccines are designed to express antigens through transgene expression of a given antigen. However, in some cases these conventional Ad-based vaccines have had sub-optimal clinical results. These sub-optimal results are attributed in part to pre-existing Ad serotype 5 (Ad5) immunity. In order to circumvent the need for antigen expression via transgene incorporation, the “antigen capsid-incorporation” strategy has been developed and used for Ad-based vaccine development in the context of a few diseases. This strategy embodies the incorporation of antigenic peptides within the capsid structure of viral vectors. The major capsid protein hexon has been utilized for these capsid incorporation strategies due to hexon's natural role in the generation of anti-Ad immune response and its numerical representation within the Ad virion. Using this strategy, we have developed the means to incorporate heterologous peptide epitopes specifically within the major surface-exposed domains of the Ad capsid protein hexon. Our study herein focuses on generation of multivalent vaccine vectors presenting HIV antigens within the Ad capsid protein hexon, as well as expressing an HIV antigen as a transgene. These novel vectors utilize HVR2 as an incorporation site for a twenty-four amino acid region of the HIV membrane proximal ectodomain region (MPER), derived from HIV glycoprotein gp41 (gp41). Our study herein illustrates that our multivalent anti-HIV vectors elicit a cellular anti-HIV response. Furthermore, vaccinations with these vectors, which present HIV antigens at HVR2, elicit a HIV epitope-specific humoral immune response.",2010 Jul 27,"['Matthews, Qiana L.', 'Fatima, Aiman', 'Tang, Yizhe', 'Perry, Brian A.', 'Tsuruta, Yuko', 'Komarova, Svetlana', 'Timares, Laura', 'Zhao, Chunxia', 'Makarova, Natalia', 'Borovjagin, Anton V.', 'Stewart, Phoebe L.', 'Wu, Hongju', 'Blackwell, Jerry L.', 'Curiel, David T.']",PLoS One,,,True
3bf0902346541d9c58458ab14fc97d2f95e2f63d,PMC,Coping flexibility in college students with depressive symptoms,http://dx.doi.org/10.1186/1477-7525-8-66,PMC2911409,20626865,CC BY,"BACKGROUND: The current study explored the prevalence of depressed mood among Chinese undergraduate students and examined the coping patterns and degree of flexibility of flexibility of such patterns associated with such mood. METHODS: A set of questionnaire assessing coping patterns, coping flexibility, and depressive symptoms were administered to 428 students (234 men and 194 women). RESULTS: A total of 266 participants both completed the entire set of questionnaires and reported a frequency of two or more stressful life events (the criterion needed to calculate variance in perceived controllability). Findings showed that higher levels of depressive symptoms were significantly associated with higher levels of both event frequency (r = .368, p < .001) and event impact (r = .245, p < .001) and lower levels of perceived controllability (r = -.261, p < .001), coping effectiveness (r = -.375, p < .001), and ratio of strategy to situation fit (r = -.108, p < .05). Depressive symptoms were not significantly associated with cognitive flexibility (variance of perceived controllability; r = .031, p = .527), Gender was not a significant moderator of any of the reported associations. CONCLUSIONS: Findings indicate that Chinese university students with depressive symptoms reported experiencing a greater number of negative events than did non-depressed university students. In addition, undergraduates with depressive symptoms were more likely than other undergraduates to utilize maladaptive coping methods. Such findings highlight the potential importance of interventions aimed at helping undergraduate students with a lower coping flexibility develop skills to cope with stressful life events.",2010 Jul 13,"['Zong, Ji-Gang', 'Cao, Xiao-Yan', 'Cao, Yuan', 'Shi, Yan-Fang', 'Wang, Yu-Na', 'Yan, Chao', 'Abela, John RZ', 'Gan, Yi-Qun', 'Gong, Qi-Yong', 'Chan, Raymond CK']",Health Qual Life Outcomes,,,True
284b00ca025a939e64aefb5129b9e942c065baaf,PMC,Vaccination with attenuated Salmonella enterica Dublin expressing E coli O157:H7 outer membrane protein Intimin induces transient reduction of fecal shedding of E coli O157:H7 in cattle,http://dx.doi.org/10.1186/1746-6148-6-35,PMC2912257,20609252,CC BY,"BACKGROUND: Escherichia coli serogroup O157:H7 has emerged as an important zoonotic bacterial pathogen, causing a range of symptoms from self-limiting bloody diarrhea to severe hemorrhagic colitis and hemolytic-uremic syndrome in humans. Beef and dairy cattle are considered the most important animal reservoirs for this pathogen. One of the important virulence characteristics of E. coli O157:H7 is the eaeA gene encoding the 97 kDa surface protein intimin. Intimin is required for attachment and effacement during the interaction of enterohemorrhagic E. coli with human and bovine neonatal enterocytes. The present study was undertaken to test the hypothesis that an adaptive mucosal immune response directed against intimin will reduce or prevent enteric colonization and fecal shedding of E. coli O157:H7 in cattle. RESULTS: Cattle were orally inoculated with either milk (control), milk with live attenuated Salmonella enterica serovar Dublin (vector), or milk with live attenuated recombinant S. Dublin expressing intimin (vaccinated) on days 0, 14 and 28. On day 98, all calves were challenged orally with E. coli O157:H7 to evaluate whether vaccination with the recombinant S. Dublin expressing intimin would reduce the level of E. coli O157:H7 fecal shedding. During the first 28 days, vaccinated calves shed both the vector strain and the intimin-expressing S. Dublin strain at a similar level. The vector strain was shed for a significantly longer period as compared to the level of recombinant vaccine strain. Calves that received the intimin-expressed vaccine ceased shedding S. Dublin from day 28 to day 63. All calves were challenged with E. coli O157:H7 on day 98 to determine the effect on fecal shedding of E. coli O157:H7. The amount of E. coli O157:H7 in feces was measured for 30 days post-challenge. We observed a transient clearance of E. coli O157:H7 from the feces in the vaccinated calves. The magnitude of fecal E. coli O157:H7 shedding did not correlate with the presence of intimin-specific fecal IgA. CONCLUSION: Oral vaccination with live attenuated recombinant S. Dublin expressing intimin reduced enteric colonization and fecal shedding of E. coli O157:H7. However, the transient clearance of E. coli O157:H7 was not associated with an enhanced IgA-mediated mucosal immune response.",2010 Jul 7,"['Khare, Sangeeta', 'Alali, Walid', 'Zhang, Shuping', 'Hunter, Doris', 'Pugh, Roberta', 'Fang, Ferric C', 'Libby, Stephen J', 'Adams, L Garry']",BMC Vet Res,,,True
8cd344d423cfae8a07936b58eb1e172fa62bcc5d,PMC,The Role of Chemokines during Viral Infection of the CNS,http://dx.doi.org/10.1371/journal.ppat.1000937,PMC2912390,20686655,CC BY,,2010 Jul 29,"['Hosking, Martin P.', 'Lane, Thomas E.']",PLoS Pathog,,,True
fa47af75688fa3fab2afde5ed3f1a7fdd9624746,PMC,Lessons from SARS: A retrospective study of outpatient care during an infectious disease outbreak,http://dx.doi.org/10.1186/1471-2431-10-51,PMC2914048,20646293,CC BY,"BACKGROUND: During severe acute respiratory syndrome (SARS) outbreak in Toronto, outpatient clinics at SickKids Hospital were closed to prevent further disease transmission. In response, a decision was made by the neonatal neuro-developmental follow up (NNFU) clinic staff to select patients with scheduled appointments to have a mail/telephone assessment using Ages and Stages Questionnaire (ASQ) or to postpone/skip their visit. The objective of this study was to compare the developmental assessment and its outcome in two groups of NNFU clinic patients, SARS versus non-SARS, over three standard clinic appointments. METHODS: We compared the diagnostic accuracy (identification of developmental delay), and patient management (referral for therapy or communication of a new diagnosis) of the strategies used during SARS, April/May 2003, to the standard assessment methods used for patients seen in April/May 2005 (non-SARS). In all cases data were obtained for 3 patient visits: before, during and after these 2 months and were compared using descriptive statistics. RESULTS: There were 95 patients in the SARS group and 99 non-SARS patients. The gestational age, sex, entry diagnosis and age at the clinic visit was not different between the groups. The NNFU clinic staff mailed ASQ to 27 families during SARS, 17 (63%) were returned, and 8 of the 17 were then contacted by telephone. Criteria used to identify infants at risk selected for either mailed ASQ or phone interviews were not clearly defined in the patients' charts. There was a significant under identification of developmental delay during SARS (18% versus 45%). Of those who responded to the mailed questionnaire, referrals for therapy rates were similar to non-SARS group. The lost to follow up rate was 24% for the SARS group compared with 7% for non-SARS. There was no difference in the overall rate of developmental delay in the two groups as identified at the 'after' visit. CONCLUSIONS: Poor advanced planning led to a haphazard assessment of patients during this infectious disease outbreak. Future pandemic plans should consider planning for outpatient care as well as in hospital management of patients.",2010 Jul 20,"['Nasef, Nehad', ""O'Brien, Karel"", 'Wylie, Lesley', 'Unger, Sharon']",BMC Pediatr,,,True
08174b668145c88e0e719dac2a03b30fb68f5de5,PMC,Serodiagnosis of Echinococcus spp. Infection: Explorative Selection of Diagnostic Antigens by Peptide Microarray,http://dx.doi.org/10.1371/journal.pntd.0000771,PMC2914747,20689813,CC BY,"BACKGROUND: Production of native antigens for serodiagnosis of helminthic infections is laborious and hampered by batch-to-batch variation. For serodiagnosis of echinococcosis, especially cystic disease, most screening tests rely on crude or purified Echinococcus granulosus hydatid cyst fluid. To resolve limitations associated with native antigens in serological tests, the use of standardized and highly pure antigens produced by chemical synthesis offers considerable advantages, provided appropriate diagnostic sensitivity and specificity is achieved. METHODOLOGY/PRINCIPAL FINDINGS: Making use of the growing collection of genomic and proteomic data, we applied a set of bioinformatic selection criteria to a collection of protein sequences including conceptually translated nucleotide sequence data of two related tapeworms, Echinococcus multilocularis and Echinococcus granulosus. Our approach targeted alpha-helical coiled-coils and intrinsically unstructured regions of parasite proteins potentially exposed to the host immune system. From 6 proteins of E. multilocularis and 5 proteins of E. granulosus, 45 peptides between 24 and 30 amino acids in length were designed. These peptides were chemically synthesized, spotted on microarrays and screened for reactivity with sera from infected humans. Peptides reacting above the cut-off were validated in enzyme-linked immunosorbent assays (ELISA). Peptides identified failed to differentiate between E. multilocularis and E. granulosus infection. The peptide performing best reached 57% sensitivity and 94% specificity. This candidate derived from Echinococcus multilocularis antigen B8/1 and showed strong reactivity to sera from patients infected either with E. multilocularis or E. granulosus. CONCLUSIONS/SIGNIFICANCE: This study provides proof of principle for the discovery of diagnostically relevant peptides by bioinformatic selection complemented with screening on a high-throughput microarray platform. Our data showed that a single peptide cannot provide sufficient diagnostic sensitivity whereas pooling several peptide antigens improved sensitivity; thus combinations of several peptides may lead the way to new diagnostic tests that replace, or at least complement conventional immunodiagnosis of echinococcosis. Our strategy could prove useful for diagnostic developments in other pathogens.",2010 Aug 3,"['List, Claudia', 'Qi, Weihong', 'Maag, Eva', 'Gottstein, Bruno', 'Müller, Norbert', 'Felger, Ingrid']",PLoS Negl Trop Dis,,,True
743c5db7611d4af74204901e0ed3b6317a0bb3c4,PMC,"Knowledge, attitudes and practices towards pandemic influenza among cases, close contacts, and healthcare workers in tropical Singapore: a cross-sectional survey",http://dx.doi.org/10.1186/1471-2458-10-442,PMC2916908,20667076,CC BY,"BACKGROUND: Effective influenza pandemic management requires understanding of the factors influencing behavioral changes. We aim to determine the differences in knowledge, attitudes and practices in various different cohorts and explore the pertinent factors that influenced behavior in tropical Singapore. METHODS: We performed a cross-sectional knowledge, attitudes and practices survey in the Singapore military from mid-August to early-October 2009, among 3054 personnel in four exposure groups - laboratory-confirmed H1N1-2009 cases, close contacts of cases, healthcare workers, and general personnel. RESULTS: 1063 (34.8%) participants responded. The mean age was 21.4 (SE 0.2) years old. Close contacts had the highest knowledge score (71.7%, p = 0.004) while cases had the highest practice scores (58.8%, p < 0.001). There was a strong correlation between knowledge and practice scores (r = 0.27, p < 0.01) and knowledge and attitudes scores (r = 0.21, p < 0.01). The significant predictors of higher practice scores were higher knowledge scores (p < 0.001), Malay ethnicity (p < 0.001), exposure group (p < 0.05) and lower education level (p < 0.05). The significant predictors for higher attitudes scores were Malay ethnicity (p = 0.014) and higher knowledge scores (p < 0.001). The significant predictor for higher knowledge score was being a contact (p = 0.007). CONCLUSION: Knowledge is a significant influence on attitudes and practices in a pandemic, and personal experience influences practice behaviors. Efforts should be targeted at educating the general population to improve practices in the current pandemic, as well as for future epidemics.",2010 Jul 28,"['Yap, Jonathan', 'Lee, Vernon J', 'Yau, Teng Yan', 'Ng, Tze Pin', 'Tor, Phern-Chern']",BMC Public Health,,,True
545def8771357b4cb2875f5795a0760e97534cc9,PMC,Knowledge and attitudes of university students toward pandemic influenza: a cross-sectional study from Turkey,http://dx.doi.org/10.1186/1471-2458-10-413,PMC2918554,20626872,CC BY,"BACKGROUND: During an influenza pandemic, higher education institutions with large populations of young adults can become serious outbreak centers. Since outbreak management is essential to disease control, we aimed to examine university students' knowledge of and attitudes toward the pandemic influenza A/H1N1 and vaccination and other preventive measures. METHODS: A cross-sectional study was conducted among 402 first year university students at Yeditepe University in Istanbul, Turkey between 1(st )and 30(th )of November 2009. Data regarding socio-demographic characteristics of the students, perceptions, level of knowledge and attitudes toward influenza pandemic and prevention measures were collected by means of a self-administered questionnaire. The questionnaire was distributed by the students affiliated with SANITAS, a university club of students in health related sciences. RESULTS: 25.1% (101/402) of the study group perceived their personal risk of influenza as ""high"", while 40.5% (163/402) perceived it as ""moderate"", 20.6% (107/402) viewed it as ""low"" and 7.7% (31/402) indicated that it was ""unknown"". The risk perception of males was significantly lower than that of females (p = 0.004) and the risk perception among the students of health sciences was significantly lower than that of students of other sciences (p = 0.037). Within the study group, 72.1% (290/402) indicated that their main information source regarding H1N1 was the mass media. Health sciences students tended to rely more on the internet as an information source than other students (p = 0.015). The vast majority (92.8%; 373/402) of those interviewed indicated that they would not be vaccinated. The major concerns regarding vaccination had to do with the safety and side effects of the vaccine. Most of the participants (343/402, 85.3%) were carrying out one of prevention measures and the vast majority believed that hand washing, face mask and quarantina were effective measures for prevention. CONCLUSION: The participants had enough knowledge about H1N1 pandemic about the disease although there were still gaps and confusions in some areas. In the future, when planning management strategies regarding pandemics or outbreaks in higher education institutions, new strategies should be developed to promote positive health behaviour among university students compatible with the international guidelines. Main information source is mass media, so it seems that new policies must be developed to attract attention of students to use different and more scientific-based information sources.",2010 Jul 13,"['Akan, Hulya', 'Gurol, Yesim', 'Izbirak, Guldal', 'Ozdatlı, Sukran', 'Yilmaz, Gulden', 'Vitrinel, Ayca', 'Hayran, Osman']",BMC Public Health,,,True
af2d96a09d1d6fcfef38c823fac66da0dcbb299e,PMC,Influenza or not influenza: Analysis of a case of high fever that happened 2000 years ago in Biblical time,http://dx.doi.org/10.1186/1743-422X-7-169,PMC2918564,20663162,CC BY,"The Bible describes the case of a woman with high fever cured by our Lord Jesus Christ. Based on the information provided by the gospels of Mark, Matthew and Luke, the diagnosis and the possible etiology of the febrile illness is discussed. Infectious diseases continue to be a threat to humanity, and influenza has been with us since the dawn of human history. If the postulation is indeed correct, the woman with fever in the Bible is among one of the very early description of human influenza disease. Infectious diseases continue to be a threat to humanity, and influenza has been with us since the dawn of human history. We analysed a case of high fever that happened 2000 years ago in Biblical time and discussed possible etiologies.",2010 Jul 21,"['Hon, Kam LE', 'Ng, Pak C', 'Leung, Ting F']",Virol J,,,True
6fc8c1b4cfbd790cbe02c825fd6f9181b1fc6645,PMC,Reassuring and managing patients with concerns about swine flu: Qualitative interviews with callers to NHS Direct,http://dx.doi.org/10.1186/1471-2458-10-451,PMC2919480,20678192,CC BY,"BACKGROUND: During the early stages of the 2009 swine flu (influenza H1N1) outbreak, the large majority of patients who contacted the health services about the illness did not have it. In the UK, the NHS Direct telephone service was used by many of these patients. We used qualitative interviews to identify the main reasons why people approached NHS Direct with concerns about swine flu and to identify aspects of their contact which were reassuring, using a framework approach. METHODS: 33 patients participated in semi-structured interviews. All patients had telephoned NHS Direct between 11 and 14 May with concerns about swine flu and had been assessed as being unlikely to have the illness. RESULTS: Reasons for seeking advice about swine flu included: the presence of unexpectedly severe flu-like symptoms; uncertainties about how one can catch swine flu; concern about giving it to others; pressure from friends or employers; and seeking 'peace of mind.' Most participants found speaking to NHS Direct reassuring or useful. Helpful aspects included: having swine flu ruled out; receiving an alternative explanation for symptoms; clarification on how swine flu is transmitted; and the perceived credibility of NHS Direct. No-one reported anything that had increased their anxiety and only one participant subsequently sought additional advice about swine flu from elsewhere. CONCLUSIONS: Future major incidents involving other forms of chemical, biological or radiological hazards may also cause large numbers of unexposed people to seek health advice. Our data suggest that providing telephone triage and information is helpful in such instances, particularly where advice can be given via a trusted, pre-existing service.",2010 Aug 2,"['Rubin, G James', 'Amlôt, Richard', 'Carter, Holly', 'Large, Shirley', 'Wessely, Simon', 'Page, Lisa']",BMC Public Health,,,True
2b0d5260ad731335898da719538d30d414a9e39f,PMC,Mixed infections with Chlamydia and porcine epidemic diarrhea virus - a new in vitro model of chlamydial persistence,http://dx.doi.org/10.1186/1471-2180-10-201,PMC2919482,20663197,CC BY,"BACKGROUND: Chlamydiae induce persistent infections, which have been associated with a wide range of chronic diseases in humans and animals. Mixed infections with Chlamydia and porcine epidemic diarrhea virus (PEDV) may result in generation of persistent chlamydial infections. To test this hypothesis, an in vitro model of dual infection with cell culture-adapted PEDV and Chlamydia abortus or Chlamydia pecorum in Vero cells was established. RESULTS: Infected cultures were investigated by immunofluorescence (IF), transmission electron microscopy (TEM) and re-infection experiments. By IF, Chlamydia-infected cells showed normal inclusions after 39 hpi. Dual infections with Chlamydia abortus revealed a heterogenous mix of inclusion types including small inclusions consisting of aberrant bodies (ABs), medium-sized inclusions consisting of ABs and reticulate bodies and normal inclusions. Only aberrant inclusions were observable in dual infection experiments with Chlamydia pecorum and PEDV. TEM examinations of mixed infections with Chlamydia abortus and Chlamydia pecorum revealed aberrant chlamydial inclusions containing reticulate-like, pleomorphic ABs, which were up to 2 μm in diameter. No re-differentiation into elementary bodies (EBs) was detected. In re-infection experiments, co-infected cells produced fewer EBs than monoinfected cells. CONCLUSIONS: In the present study we confirm that PEDV co-infection alters the developmental cycle of member species of the family Chlamydiaceae, in a similar manner to other well-described persistence induction methods. Interestingly, this effect appears to be partially species-specific as Chlamydia pecorum appears more sensitive to PEDV co-infection than Chlamydia abortus, as evidenced by TEM and IF observations of a homogenous population of aberrant inclusions in PEDV - Chlamydia pecorum co-infections.",2010 Jul 27,"['Borel, Nicole', 'Dumrese, Claudia', 'Ziegler, Urs', 'Schifferli, Andrea', 'Kaiser, Carmen', 'Pospischil, Andreas']",BMC Microbiol,,,True
aa1f783a1af8b14cdbee5ea50cc0a78c56d7442e,PMC,Protective Efficacy of Cross-Reactive CD8(+) T Cells Recognising Mutant Viral Epitopes Depends on Peptide-MHC-I Structural Interactions and T Cell Activation Threshold,http://dx.doi.org/10.1371/journal.ppat.1001039,PMC2920842,20711359,CC BY,"Emergence of a new influenza strain leads to a rapid global spread of the virus due to minimal antibody immunity. Pre-existing CD8(+) T-cell immunity directed towards conserved internal viral regions can greatly ameliorate the disease. However, mutational escape within the T cell epitopes is a substantial issue for virus control and vaccine design. Although mutations can result in a loss of T cell recognition, some variants generate cross-reactive T cell responses. In this study, we used reverse genetics to modify the influenza NP(336–374) peptide at a partially-solvent exposed residue (N->A, NPN3A mutation) to assess the availability, effectiveness and mechanism underlying influenza-specific cross-reactive T cell responses. The engineered virus induced a diminished CD8(+) T cell response and selected a narrowed T cell receptor (TCR) repertoire within two Vβ regions (Vβ8.3 and Vβ9). This can be partially explained by the H-2D(b)NPN3A structure that showed a loss of several contacts between the NPN3A peptide and H-2D(b), including a contact with His155, a position known to play an important role in mediating TCR-pMHC-I interactions. Despite these differences, common cross-reactive TCRs were detected in both the naïve and immune NPN3A-specific TCR repertoires. However, while the NPN3A epitope primes memory T-cells that give an equivalent recall response to the mutant or wild-type (wt) virus, both are markedly lower than wt->wt challenge. Such decreased CD8(+) responses elicited after heterologous challenge resulted in delayed viral clearance from the infected lung. Furthermore, mice first exposed to the wt virus give a poor, low avidity response following secondary infection with the mutant. Thus, the protective efficacy of cross-reactive CD8(+) T cells recognising mutant viral epitopes depend on peptide-MHC-I structural interactions and functional avidity. Our study does not support vaccine strategies that include immunization against commonly selected cross-reactive variants with mutations at partially-solvent exposed residues that have characteristics comparable to NPN3A.",2010 Aug 12,"['Valkenburg, Sophie A.', 'Gras, Stephanie', 'Guillonneau, Carole', 'La Gruta, Nicole L.', 'Thomas, Paul G.', 'Purcell, Anthony W.', 'Rossjohn, Jamie', 'Doherty, Peter C.', 'Turner, Stephen J.', 'Kedzierska, Katherine']",PLoS Pathog,,,True
afc498abcb287239b8ea84ff535adf09158b0cfe,PMC,ANDES: Statistical tools for the ANalyses of DEep Sequencing,http://dx.doi.org/10.1186/1756-0500-3-199,PMC2921379,20633290,CC BY,"BACKGROUND: The advancements in DNA sequencing technologies have allowed researchers to progress from the analyses of a single organism towards the deep sequencing of a sample of organisms. With sufficient sequencing depth, it is now possible to detect subtle variations between members of the same species, or between mixed species with shared biomarkers, such as the 16S rRNA gene. However, traditional sequencing analyses of samples from largely homogeneous populations are often still based on multiple sequence alignments (MSA), where each sequence is placed along a separate row and similarities between aligned bases can be followed down each column. While this visual format is intuitive for a small set of aligned sequences, the representation quickly becomes cumbersome as sequencing depths cover loci hundreds or thousands of reads deep. FINDINGS: We have developed ANDES, a software library and a suite of applications, written in Perl and R, for the statistical ANalyses of DEep Sequencing. The fundamental data structure underlying ANDES is the position profile, which contains the nucleotide distributions for each genomic position resultant from a multiple sequence alignment (MSA). Tools include the root mean square deviation (RMSD) plot, which allows for the visual comparison of multiple samples on a position-by-position basis, and the computation of base conversion frequencies (transition/transversion rates), variation (Shannon entropy), inter-sample clustering and visualization (dendrogram and multidimensional scaling (MDS) plot), threshold-driven consensus sequence generation and polymorphism detection, and the estimation of empirically determined sequencing quality values. CONCLUSIONS: As new sequencing technologies evolve, deep sequencing will become increasingly cost-efficient and the inter and intra-sample comparisons of largely homogeneous sequences will become more common. We have provided a software package and demonstrated its application on various empirically-derived datasets. Investigators may download the software from Sourceforge at https://sourceforge.net/projects/andestools.",2010 Jul 15,"['Li, Kelvin', 'Venter, Eli', 'Yooseph, Shibu', 'Stockwell, Timothy B', 'Eckerle, Lance D', 'Denison, Mark R', 'Spiro, David J', 'Methé, Barbara A']",BMC Res Notes,,,True
40a30eb6f76c29d52d4ee9c7619f9f8bbfef796a,PMC,Perceptions and behaviors related to hand hygiene for the prevention of H1N1 influenza transmission among Korean university students during the peak pandemic period,http://dx.doi.org/10.1186/1471-2334-10-222,PMC2922213,20663229,CC BY,"BACKGROUND: This study was performed to better assess the perceptions, motivating factors, and behaviors associated with the use of hand washing to prevent H1N1 influenza transmission during the peak pandemic period in Korea. METHODS: A cross-sectional survey questionnaire was completed by 942 students at a university campus in Suwon, Korea, between December 1 and 8, 2009. The survey included questions regarding individual perceptions, motivating factors, and behaviors associated with hand washing for the prevention of H1N1 influenza transmission. RESULTS: Compared to one year prior, 30.3% of participants reported increasing their hand washing frequency. Female students were more likely to practice more frequent hand washing. Women also perceived the effectiveness of hand washing to be lower, and illness severity and personal susceptibility to H1N1 infection to be higher. Study participants who were female (OR: 1.79-3.90) who perceived of hand washing to be effective (OR: 1.34-12.15) and illness severity to be greater (OR: 1.00-3.12) washed their hands more frequently. CONCLUSIONS: Korean students increased their frequency of hand hygiene practices during the pandemic, with significant gender differences existing in the attitudes and behaviors related to the use of hand hygiene as a means of disease prevention. Here, the factors that affected hand washing behavior were similar to those identified at the beginning of the H1N1 or SARS pandemics, suggesting that public education campaigns regarding hand hygiene are effective in altering individual hand hygiene habits during the peak periods of influenza transmission.",2010 Jul 28,"['Park, Jae-Hyun', 'Cheong, Hae-Kwan', 'Son, Dae-Yong', 'Kim, Seon-Ung', 'Ha, Chang-Min']",BMC Infect Dis,,,True
1552cf77b6385950e197c67c2ed55ed6e1879ced,PMC,"Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold",http://dx.doi.org/10.1186/1465-9921-11-108,PMC2923116,20696083,CC BY,"BACKGROUND: The common cold, the most prevalent contagious viral disease in humans still lacks a safe and effective antiviral treatment. Iota-Carrageenan is broadly active against respiratory viruses in-vitro and has an excellent safety profile. This study investigated the efficacy and safety of an Iota-Carrageenan nasal spray in patients with common cold symptoms. METHODS: In a randomized, double-blind, placebo-controlled exploratory trial, 35 human subjects suffering from early symptoms of common cold received Iota-Carrageenan (0.12%) in a saline solution three times daily for 4 days, compared to placebo. RESULTS: Administration of Iota-Carrageenan nasal spray reduced the symptoms of common cold (p = 0.046) and the viral load in nasal lavages (p = 0.009) in patients with early symptoms of common cold. Pro-inflammatory mediators FGF-2, Fractalkine, GRO, G-CSF, IL-8, IL-1α, IP-10, IL-10, and IFN-α2 were reduced in the Iota-Carrageenan group. CONCLUSIONS: Iota-Carrageenan nasal spray appears to be a promising treatment for safe and effective treatment of early symptoms of common cold. Larger trials are indicated to confirm the results.",2010 Aug 10,"['Eccles, Ron', 'Meier, Christiane', 'Jawad, Martez', 'Weinmüllner, Regina', 'Grassauer, Andreas', 'Prieschl-Grassauer, Eva']",Respir Res,,,True
95c1dc78f1775a83d61ad2517a26844f9a3c46b9,PMC,Enterovirus type 71 2A protease functions as a transcriptional activator in yeast,http://dx.doi.org/10.1186/1423-0127-17-65,PMC2923119,20682079,CC BY,"Enterovirus type 71 (EV71) 2A protease exhibited strong transcriptional activity in yeast cells. The transcriptional activity of 2A protease was independent of its protease activity. EV71 2A protease retained its transcriptional activity after truncation of 40 amino acids at the N-terminus but lost this activity after truncation of 60 amino acids at the N-terminus or deletion of 20 amino acids at the C-terminus. Thus, the acidic domain at the C-terminus of this protein is essential for its transcriptional activity. Indeed, deletion of amino acids from 146 to 149 (EAME) in this acidic domain lost the transcriptional activity of EV71 2A protein though still retained its protease activity. EV71 2A protease was detected both in the cytoplasm and nucleus using confocal microscopy analysis. Coxsackie virus B3 2A protease also exhibited transcriptional activity in yeast cells. As expected, an acidic domain in the C-terminus of Coxsackie virus B3 2A protease was also identified. Truncation of this acidic domain resulted in the loss of transcriptional activity. Interestingly, this acidic region of poliovirus 2A protease is critical for viral RNA replication. The transcriptional activity of the EV71 or Coxsackie virus B3 2A protease should play a role in viral replication and/or pathogenesis.",2010 Aug 4,"['Yang, Chee-Hing', 'Li, Hui-Chun', 'Jiang, Jeng-Geng', 'Hsu, Che-Fang', 'Wang, Yi-Jen', 'Lai, Meng-Jiun', 'Juang, Yue-Li', 'Lo, Shih-Yen']",J Biomed Sci,,,True
ab371ed38caa53c720fd4c0333e1bf4de84550f1,PMC,Cancer Biomarker Discovery: The Entropic Hallmark,http://dx.doi.org/10.1371/journal.pone.0012262,PMC2923618,20805891,CC BY,"BACKGROUND: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. METHODOLOGY/PRINCIPAL FINDINGS: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. CONCLUSIONS/SIGNIFICANCE: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-througput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases.",2010 Aug 18,"['Berretta, Regina', 'Moscato, Pablo']",PLoS One,,,True
a0016598cd0ea40803d8ab461f4ebdba9abe94c1,PMC,Adaptive Contact Networks Change Effective Disease Infectiousness and Dynamics,http://dx.doi.org/10.1371/journal.pcbi.1000895,PMC2924249,20808884,CC BY,"Human societies are organized in complex webs that are constantly reshaped by a social dynamic which is influenced by the information individuals have about others. Similarly, epidemic spreading may be affected by local information that makes individuals aware of the health status of their social contacts, allowing them to avoid contact with those infected and to remain in touch with the healthy. Here we study disease dynamics in finite populations in which infection occurs along the links of a dynamical contact network whose reshaping may be biased based on each individual's health status. We adopt some of the most widely used epidemiological models, investigating the impact of the reshaping of the contact network on the disease dynamics. We derive analytical results in the limit where network reshaping occurs much faster than disease spreading and demonstrate numerically that this limit extends to a much wider range of time scales than one might anticipate. Specifically, we show that from a population-level description, disease propagation in a quickly adapting network can be formulated equivalently as disease spreading on a well-mixed population but with a rescaled infectiousness. We find that for all models studied here – SI, SIS and SIR – the effective infectiousness of a disease depends on the population size, the number of infected in the population, and the capacity of healthy individuals to sever contacts with the infected. Importantly, we indicate how the use of available information hinders disease progression, either by reducing the average time required to eradicate a disease (in case recovery is possible), or by increasing the average time needed for a disease to spread to the entire population (in case recovery or immunity is impossible).",2010 Aug 19,"['Van Segbroeck, Sven', 'Santos, Francisco C.', 'Pacheco, Jorge M.']",PLoS Comput Biol,,,True
d61d66e22524793eb025db202a84eaaae50da2bf,PMC,Adaptive Contact Networks Change Effective Disease Infectiousness and Dynamics,http://dx.doi.org/10.1371/journal.pcbi.1000895,PMC2924249,20808884,CC BY,"Human societies are organized in complex webs that are constantly reshaped by a social dynamic which is influenced by the information individuals have about others. Similarly, epidemic spreading may be affected by local information that makes individuals aware of the health status of their social contacts, allowing them to avoid contact with those infected and to remain in touch with the healthy. Here we study disease dynamics in finite populations in which infection occurs along the links of a dynamical contact network whose reshaping may be biased based on each individual's health status. We adopt some of the most widely used epidemiological models, investigating the impact of the reshaping of the contact network on the disease dynamics. We derive analytical results in the limit where network reshaping occurs much faster than disease spreading and demonstrate numerically that this limit extends to a much wider range of time scales than one might anticipate. Specifically, we show that from a population-level description, disease propagation in a quickly adapting network can be formulated equivalently as disease spreading on a well-mixed population but with a rescaled infectiousness. We find that for all models studied here – SI, SIS and SIR – the effective infectiousness of a disease depends on the population size, the number of infected in the population, and the capacity of healthy individuals to sever contacts with the infected. Importantly, we indicate how the use of available information hinders disease progression, either by reducing the average time required to eradicate a disease (in case recovery is possible), or by increasing the average time needed for a disease to spread to the entire population (in case recovery or immunity is impossible).",2010 Aug 19,"['Van Segbroeck, Sven', 'Santos, Francisco C.', 'Pacheco, Jorge M.']",PLoS Comput Biol,,,True
217e7ecb495478a12b89de6ab9d03e629f478752,PMC,Up-regulation of p21 and TNF-α is mediated in lycorine-induced death of HL-60 cells,http://dx.doi.org/10.1186/1475-2867-10-25,PMC2924328,20682078,CC BY,"BACKGROUND: Leukemia is one of the most life-threatening cancers today, and acute promyelogenous leukemia (APL) is a common type of leukemia. Many natural compounds have already been found to exhibit significant anti-tumor effects. Lycorine, a natural alkaloid extracted from Amaryllidaceae, exhibited anti-leukemia effects in vitro and in vivo. The survival rate of HL-60 cells exposed to lycorine was decreased, cell growth was slowed down, and cell regeneration potential was inhibited. HL-60 cells exhibited typical apoptotic characteristic. Lycorine can suppress leukemia growth and reduce cell survival and inducing apoptosis of tumor cells. The purpose of this work is to elucidate the mechanism by which lycorine induces APL cells. RESULTS: When HL-60 cells were treated with different concentration of lycorine, the expression of p21 and TNF-α was up-regulated in a concentration-dependent manner as shown by real-time quantitative reverse transcriptase-polymerase chain reaction and Western blotting. Lycorine also down-regulated p21-related gene expression, including Cdc2, Cyclin B, Cdk2 and Cyclin E, promoted Bid truncation, decreased IκB phosphorylation and blocked NF-κB nuclear import. Cytochrome c was released from mitochondria as observed with confocal laser microscopy. CONCLUSIONS: The TNF-α signal transduction pathway and p21-mediated cell-cycle inhibition were involved in the apoptosis of HL-60 cells induced by lycorine. These results contribute to the development of new lycorine-based anti-leukemia drugs.",2010 Aug 4,"['Liu, Jing', 'Hu, Ji-liang', 'Shi, Bi-Wei', 'He, Yan', 'Hu, Wei-Xin']",Cancer Cell Int,,,True
ffaa82089f00d6e0b4710f59b4016c59c5879ea7,PMC,Diagnostic Methods for Feline Coronavirus: A Review,http://dx.doi.org/10.4061/2010/809480,PMC2926681,20798771,CC BY,"Feline coronaviruses (FCoVs) are found throughout the world. Infection with FCoV can result in a diverse range of signs from clinically inapparent infections to a highly fatal disease called feline infectious peritonitis (FIP). FIP is one of the most serious viral diseases of cats. While there is neither an effective vaccine, nor a curative treatment for FIP, a diagnostic protocol for FCoV would greatly assist in the management and control of the virus. Clinical findings in FIP are non-specific and not helpful in making a differential diagnosis. Haematological and biochemical abnormalities in FIP cases are also non-specific. The currently available serological tests have low specificity and sensitivity for detection of active infection and cross-react with FCoV strains of low pathogenicity, the feline enteric coronaviruses (FECV). Reverse transcriptase polymerase chain reaction (RT-PCR) has been used to detect FCoV and is rapid and sensitive, but results must be interpreted in the context of clinical findings. At present, a definitive diagnosis of FIP can be established only by histopathological examination of biopsies. This paper describes and compares diagnostic methods for FCoVs and includes a brief account of the virus biology, epidemiology, and pathogenesis.",2010 Jul 28,"['Sharif, Saeed', 'Arshad, Siti Suri', 'Hair-Bejo, Mohd', 'Omar, Abdul Rahman', 'Zeenathul, Nazariah Allaudin', 'Alazawy, Amer']",Vet Med Int,,,True
7875c1a9783593b90bb90b99f285583067a3f433,PMC,Establishment of Fruit Bat Cells (Rousettus aegyptiacus) as a Model System for the Investigation of Filoviral Infection,http://dx.doi.org/10.1371/journal.pntd.0000802,PMC2927428,20808767,CC BY,"BACKGROUND: The fruit bat species Rousettus aegyptiacus was identified as a potential reservoir for the highly pathogenic filovirus Marburg virus. To establish a basis for a molecular understanding of the biology of filoviruses in the reservoir host, we have adapted a set of molecular tools for investigation of filovirus replication in a recently developed cell line, R06E, derived from the species Rousettus aegyptiacus. METHODOLOGY/PRINCIPAL FINDINGS: Upon infection with Ebola or Marburg viruses, R06E cells produced viral titers comparable to VeroE6 cells, as shown by TCID(50) analysis. Electron microscopic analysis of infected cells revealed morphological signs of filovirus infection as described for human- and monkey-derived cell lines. Using R06E cells, we detected an unusually high amount of intracellular viral proteins, which correlated with the accumulation of high numbers of filoviral nucleocapsids in the cytoplasm. We established protocols to produce Marburg infectious virus-like particles from R06E cells, which were then used to infect naïve target cells to investigate primary transcription. This was not possible with other cell lines previously tested. Moreover, we established protocols to reliably rescue recombinant Marburg viruses from R06E cells. CONCLUSION/SIGNIFICANCE: These data indicated that R06E cells are highly suitable to investigate the biology of filoviruses in cells derived from their presumed reservoir.",2010 Aug 24,"['Krähling, Verena', 'Dolnik, Olga', 'Kolesnikova, Larissa', 'Schmidt-Chanasit, Jonas', 'Jordan, Ingo', 'Sandig, Volker', 'Günther, Stephan', 'Becker, Stephan']",PLoS Negl Trop Dis,,,True
eb6bcd87e93e2bac6bd7b03367102b0a05e458e3,PMC,Ferret badger rabies origin and its revisited importance as potential source of rabies transmission in Southeast China,http://dx.doi.org/10.1186/1471-2334-10-234,PMC2927599,20691095,CC BY,"BACKGROUND: The frequent occurrence of ferret badger-associated human rabies cases in southeast China highlights the lack of laboratory-based surveillance and urges revisiting the potential importance of this animal in rabies transmission. To determine if the ferret badgers actually contribute to human and dog rabies cases, and the possible origin of the ferret badger-associated rabies in the region, an active rabies survey was conducted to determine the frequency of rabies infection and seroprevalence in dogs and ferret badgers. METHODS: A retrospective survey on rabies epidemics was performed in Zhejiang, Jiangxi and Anhui provinces in southeast China. The brain tissues from ferret badgers and dogs were assayed by fluorescent antibody test. Rabies virus was isolated and sequenced for phylogenetic analysis. The sera from ferret badgers and dogs were titrated using rabies virus neutralizing antibodies (VNA) test. RESULTS: The ferret badgers presented a higher percentage of rabies seroconversion than dogs did in the endemic region, reaching a maximum of 95% in the collected samples. Nine ferret badger-associated rabies viruses were isolated, sequenced, and were phylogenetically clustered as a separate group. Nucleotide sequence revealed 99.4-99.8% homology within the ferret badger isolates, and 83-89% homology to the dog isolates in the nucleoprotein and glycoprotein genes in the same rabies endemic regions. CONCLUSIONS: Our data suggest ferret badger-associated rabies has likely formed as an independent enzootic originating from dogs during the long-term rabies infestation in southeast China. The eventual role of FB rabies in public health remains unclear. However, management of ferret badger bites, rabies awareness and control in the related regions should be an immediate need.",2010 Aug 6,"['Liu, Ye', 'Zhang, Shoufeng', 'Wu, Xianfu', 'Zhao, Jinghui', 'Hou, Yanli', 'Zhang, Fei', 'Velasco-Villa, Andres', 'Rupprecht, Charles E', 'Hu, Rongliang']",BMC Infect Dis,,,True
8a1127271041cb420bec9aa4be4afa5d62b2b3b7,PMC,Proteomics Comparison of Cerebrospinal Fluid of Relapsing Remitting and Primary Progressive Multiple Sclerosis,http://dx.doi.org/10.1371/journal.pone.0012442,PMC2929207,20805994,CC BY,"BACKGROUND: Based on clinical representation of disease symptoms multiple sclerosis (MScl) patients can be divided into two major subtypes; relapsing remitting (RR) MScl (85–90%) and primary progressive (PP) MScl (10–15%). Proteomics analysis of cerebrospinal fluid (CSF) has detected a number of proteins that were elevated in MScl patients. Here we specifically aimed to differentiate between the PP and RR subtypes of MScl by comparing CSF proteins. METHODOLOGY/PRINCIPAL FINDINGS: CSF samples (n = 31) were handled according to the same protocol for quantitative mass spectrometry measurements we reported previously. In the comparison of PP MScl versus RR MScl we observed a number of differentially abundant proteins, such as protein jagged-1 and vitamin D-binding protein. Protein jagged-1 was over three times less abundant in PP MScl compared to RR MScl. Vitamin D-binding protein was only detected in the RR MScl samples. These two proteins were validated by independent techniques (western blot and ELISA) as differentially abundant in the comparison between both MScl types. CONCLUSIONS/SIGNIFICANCE: The main finding of this comparative study is the observation that the proteome profiles of CSF in PP and RR MScl patients overlap to a large extent. Still, a number of differences could be observed. Protein jagged-1 is a ligand for multiple Notch receptors and involved in the mediation of Notch signaling. It is suggested in literature that the Notch pathway is involved in the remyelination of MScl lesions. Aberration of normal homeostasis of Vitamin D, of which approximately 90% is bound to vitamin D-binding protein, has been widely implicated in MScl for some years now. Vitamin D directly and indirectly regulates the differentiation, activation of CD4+ T-lymphocytes and can prevent the development of autoimmune processes, and so it may be involved in neuroprotective elements in MScl.",2010 Aug 27,"['Stoop, Marcel P.', 'Singh, Vaibhav', 'Dekker, Lennard J.', 'Titulaer, Mark K.', 'Stingl, Christoph', 'Burgers, Peter C.', 'Sillevis Smitt, Peter A. E.', 'Hintzen, Rogier Q.', 'Luider, Theo M.']",PLoS One,,,True
797c6ecb7d0eb5d6eb5ea5f081a3c4cc78be5bd2,PMC,Including the public in pandemic planning: a deliberative approach,http://dx.doi.org/10.1186/1471-2458-10-501,PMC2931476,20718996,CC BY,"BACKGROUND: Against a background of pandemic threat posed by SARS and avian H5N1 influenza, this study used deliberative forums to elucidate informed community perspectives on aspects of pandemic planning. METHODS: Two deliberative forums were carried out with members of the South Australian community. The forums were supported by a qualitative study with adults and youths, systematic reviews of the literature and the involvement of an extended group of academic experts and policy makers. The forum discussions were recorded with simultaneous transcription and analysed thematically. RESULTS: Participants allocated scarce resources of antiviral drugs and pandemic vaccine based on a desire to preserve society function in a time of crisis. Participants were divided on the acceptability of social distancing and quarantine measures. However, should such measures be adopted, they thought that reasonable financial, household and psychological support was essential. In addition, provided such support was present, the participants, in general, were willing to impose strict sanctions on those who violated quarantine and social distancing measures. CONCLUSIONS: The recommendations from the forums suggest that the implementation of pandemic plans in a severe pandemic will be challenging, but not impossible. Implementation may be more successful if the public is engaged in pandemic planning before a pandemic, effective communication of key points is practiced before and during a pandemic and if judicious use is made of supportive measures to assist those in quarantine or affected by social isolation measures.",2010 Aug 19,"['Braunack-Mayer, Annette J', 'Street, Jackie M', 'Rogers, Wendy A', 'Givney, Rodney', 'Moss, John R', 'Hiller, Janet E']",BMC Public Health,,,True
6598644894c24fccef62e4df45e859f023bea4c6,PMC,Risk factors for the evolutionary emergence of pathogens,http://dx.doi.org/10.1098/rsif.2010.0123,PMC2935601,20410190,CC BY,"Recent outbreaks of novel infectious diseases (e.g. SARS, influenza H1N1) have highlighted the threat of cross-species pathogen transmission. When first introduced to a population, a pathogen is often poorly adapted to its new host and must evolve in order to escape extinction. Theoretical arguments and empirical studies have suggested various factors to explain why some pathogens emerge and others do not, including host contact structure, pathogen adaptive pathways and mutation rates. Using a multi-type branching process, we model the spread of an introduced pathogen evolving through several strains. Extending previous models, we use a network-based approach to separate host contact patterns from pathogen transmissibility. We also allow for arbitrary adaptive pathways. These generalizations lead to novel predictions regarding the impact of hypothesized risk factors. Pathogen fitness depends on the host population in which it circulates, and the ‘riskiest’ contact distribution and adaptive pathway depend on initial transmissibility. Emergence probability is sensitive to mutation probabilities and number of adaptive steps required, with the possibility of large adaptive steps (e.g. simultaneous point mutations or recombination) having a dramatic effect. In most situations, increasing overall mutation probability increases the risk of emergence; however, notable exceptions arise when deleterious mutations are available.",2010 Oct 6,"['Alexander, H. K.', 'Day, T.']",J R Soc Interface,,,True
b1d31bf64148c3dabdd5b8a288b78c0c6d3a7cea,PMC,Curating the innate immunity interactome,http://dx.doi.org/10.1186/1752-0509-4-117,PMC2936296,20727158,CC BY,"BACKGROUND: The innate immune response is the first line of defence against invading pathogens and is regulated by complex signalling and transcriptional networks. Systems biology approaches promise to shed new light on the regulation of innate immunity through the analysis and modelling of these networks. A key initial step in this process is the contextual cataloguing of the components of this system and the molecular interactions that comprise these networks. InnateDB (http://www.innatedb.com) is a molecular interaction and pathway database developed to facilitate systems-level analyses of innate immunity. RESULTS: Here, we describe the InnateDB curation project, which is manually annotating the human and mouse innate immunity interactome in rich contextual detail, and present our novel curation software system, which has been developed to ensure interactions are curated in a highly accurate and data-standards compliant manner. To date, over 13,000 interactions (protein, DNA and RNA) have been curated from the biomedical literature. Here, we present data, illustrating how InnateDB curation of the innate immunity interactome has greatly enhanced network and pathway annotation available for systems-level analysis and discuss the challenges that face such curation efforts. Significantly, we provide several lines of evidence that analysis of the innate immunity interactome has the potential to identify novel signalling, transcriptional and post-transcriptional regulators of innate immunity. Additionally, these analyses also provide insight into the cross-talk between innate immunity pathways and other biological processes, such as adaptive immunity, cancer and diabetes, and intriguingly, suggests links to other pathways, which as yet, have not been implicated in the innate immune response. CONCLUSIONS: In summary, curation of the InnateDB interactome provides a wealth of information to enable systems-level analysis of innate immunity.",2010 Aug 20,"['Lynn, David J', 'Chan, Calvin', 'Naseer, Misbah', 'Yau, Melissa', 'Lo, Raymond', 'Sribnaia, Anastasia', 'Ring, Giselle', 'Que, Jaimmie', 'Wee, Kathleen', 'Winsor, Geoffrey L', 'Laird, Matthew R', 'Breuer, Karin', 'Foroushani, Amir K', 'Brinkman, Fiona SL', 'Hancock, Robert EW']",BMC Syst Biol,,,True
1b5d310d0656503b1d2fbc612625496a3266ae16,PMC,Serological characterization of guinea pigs infected with H3N2 human influenza or immunized with hemagglutinin protein,http://dx.doi.org/10.1186/1743-422X-7-200,PMC2939558,20735849,CC BY,"BACKGROUND: Recent and previous studies have shown that guinea pigs can be infected with, and transmit, human influenza viruses. Therefore guinea pig may be a useful animal model for better understanding influenza infection and assessing vaccine strategies. To more fully characterize the model, antibody responses following either infection/re-infection with human influenza A/Wyoming/03/2003 H3N2 or immunization with its homologous recombinant hemagglutinin (HA) protein were studied. RESULTS: Serological samples were collected and tested for anti-HA immunoglobulin by ELISA, antiviral antibodies by hemagglutination inhibition (HI), and recognition of linear epitopes by peptide scanning (PepScan). Animals inoculated with infectious virus demonstrated pronounced viral replication and subsequent serological conversion. Animals either immunized with the homologous HA antigen or infected, showed a relatively rapid rise in antibody titers to the HA glycoprotein in ELISA assays. Antiviral antibodies, measured by HI assay, were detectable after the second inoculation. PepScan data identified both previously recognized and newly defined linear epitopes. CONCLUSIONS: Infection and/or recombinant HA immunization of guinea pigs with H3N2 Wyoming influenza virus resulted in a relatively rapid production of viral-specific antibody thus demonstrating the strong immunogenicity of the major viral structural proteins in this animal model for influenza infection. The sensitivity of the immune response supports the utility of the guinea pig as a useful animal model of influenza infection and immunization.",2010 Aug 24,"['Bushnell, Ruth V', 'Tobin, John K', 'Long, Jinxue', 'Schultz-Cherry, Stacey', 'Chaudhuri, A Ray', 'Nara, Peter L', 'Tobin, Gregory J']",Virol J,,,True
24d774f5b08d9ca987d0d23927d92ba23f131931,PMC,Detection of swine transmissible gastroenteritis coronavirus using loop-mediated isothermal amplification,http://dx.doi.org/10.1186/1743-422X-7-206,PMC2939561,20799985,CC BY,"A conserved nucleic acid fragment of the nucleocapsid gene of Swine Transmissible Gastroenteritis Coronavirus (TGEV) was chosen as the target, six special primers were designed successfully. Loop-mediated isothermal amplification (LAMP) was developed to detect the TGEV by incubation at 60°C for 1 h and the product specificity was confirmed by HphI digestion. Standard curves with high accuracy for TGEV quantization was constructed by adding 1 × SYBR greenI in the LAMP reaction. The assay established in this study was found to detect only the TGEV and no cross-reaction with other viruses, demonstrating its high specificity. By using serial sample dilutions as templates, the detection limit of LAMP was about 10 pg RNA, 10 times more sensitive than that of PCR and could be comparable to the nest-PCR.",2010 Aug 29,"['Chen, Qin', 'Li, Jian', 'Fang, Xue-En', 'Xiong, Wei']",Virol J,,,True
22f1e46f69ea11771ee26f499b234bd3ff1bb88b,PMC,Predictive Power of Air Travel and Socio-Economic Data for Early Pandemic Spread,http://dx.doi.org/10.1371/journal.pone.0012763,PMC2939898,20856678,CC BY,"BACKGROUND: Controlling the pandemic spread of newly emerging diseases requires rapid, targeted allocation of limited resources among nations. Critical, early control steps would be greatly enhanced if the key risk factors can be identified that accurately predict early disease spread immediately after emergence. METHODOLOGY/PRINCIPAL FINDINGS: Here, we examine the role of travel, trade, and national healthcare resources in predicting the emergence and initial spread of 2009 A/H1N1 influenza. We find that incorporating national healthcare resource data into our analyses allowed a much greater capacity to predict the international spread of this virus. In countries with lower healthcare resources, the reporting of 2009 A/H1N1 cases was significantly delayed, likely reflecting a lower capacity for testing and reporting, as well as other socio-political issues. We also report substantial international trade in live swine and poultry in the decade preceding the pandemic which may have contributed to the emergence and mixed genotype of this pandemic strain. However, the lack of knowledge of recent evolution of each H1N1 viral gene segment precludes the use of this approach to determine viral origins. CONCLUSIONS/SIGNIFICANCE: We conclude that strategies to prevent pandemic influenza virus emergence and spread in the future should include: 1) enhanced surveillance for strains resulting from reassortment in traded livestock; 2) rapid deployment of control measures in the initial spreading phase to countries where travel data predict the pathogen will reach and to countries where lower healthcare resources will likely cause delays in reporting. Our results highlight the benefits, for all parties, when higher income countries provide additional healthcare resources for lower income countries, particularly those that have high air traffic volumes. In particular, international authorities should prioritize aid to those poorest countries where both the risk of emerging infectious diseases and air traffic volume is highest. This strategy will result in earlier detection of pathogens and a reduction in the impact of future pandemics.",2010 Sep 15,"['Hosseini, Parviez', 'Sokolow, Susanne H.', 'Vandegrift, Kurt J.', 'Kilpatrick, A. Marm', 'Daszak, Peter']",PLoS One,,,True
9d2d0abefdd08e5ab7311a1f9dd2c8ad9d34d4dd,PMC,Predictive Power of Air Travel and Socio-Economic Data for Early Pandemic Spread,http://dx.doi.org/10.1371/journal.pone.0012763,PMC2939898,20856678,CC BY,"BACKGROUND: Controlling the pandemic spread of newly emerging diseases requires rapid, targeted allocation of limited resources among nations. Critical, early control steps would be greatly enhanced if the key risk factors can be identified that accurately predict early disease spread immediately after emergence. METHODOLOGY/PRINCIPAL FINDINGS: Here, we examine the role of travel, trade, and national healthcare resources in predicting the emergence and initial spread of 2009 A/H1N1 influenza. We find that incorporating national healthcare resource data into our analyses allowed a much greater capacity to predict the international spread of this virus. In countries with lower healthcare resources, the reporting of 2009 A/H1N1 cases was significantly delayed, likely reflecting a lower capacity for testing and reporting, as well as other socio-political issues. We also report substantial international trade in live swine and poultry in the decade preceding the pandemic which may have contributed to the emergence and mixed genotype of this pandemic strain. However, the lack of knowledge of recent evolution of each H1N1 viral gene segment precludes the use of this approach to determine viral origins. CONCLUSIONS/SIGNIFICANCE: We conclude that strategies to prevent pandemic influenza virus emergence and spread in the future should include: 1) enhanced surveillance for strains resulting from reassortment in traded livestock; 2) rapid deployment of control measures in the initial spreading phase to countries where travel data predict the pathogen will reach and to countries where lower healthcare resources will likely cause delays in reporting. Our results highlight the benefits, for all parties, when higher income countries provide additional healthcare resources for lower income countries, particularly those that have high air traffic volumes. In particular, international authorities should prioritize aid to those poorest countries where both the risk of emerging infectious diseases and air traffic volume is highest. This strategy will result in earlier detection of pathogens and a reduction in the impact of future pandemics.",2010 Sep 15,"['Hosseini, Parviez', 'Sokolow, Susanne H.', 'Vandegrift, Kurt J.', 'Kilpatrick, A. Marm', 'Daszak, Peter']",PLoS One,,,False
8228f444067a2fb0122111798ff462a4a92b59a6,PMC,Predictive Power of Air Travel and Socio-Economic Data for Early Pandemic Spread,http://dx.doi.org/10.1371/journal.pone.0012763,PMC2939898,20856678,CC BY,"BACKGROUND: Controlling the pandemic spread of newly emerging diseases requires rapid, targeted allocation of limited resources among nations. Critical, early control steps would be greatly enhanced if the key risk factors can be identified that accurately predict early disease spread immediately after emergence. METHODOLOGY/PRINCIPAL FINDINGS: Here, we examine the role of travel, trade, and national healthcare resources in predicting the emergence and initial spread of 2009 A/H1N1 influenza. We find that incorporating national healthcare resource data into our analyses allowed a much greater capacity to predict the international spread of this virus. In countries with lower healthcare resources, the reporting of 2009 A/H1N1 cases was significantly delayed, likely reflecting a lower capacity for testing and reporting, as well as other socio-political issues. We also report substantial international trade in live swine and poultry in the decade preceding the pandemic which may have contributed to the emergence and mixed genotype of this pandemic strain. However, the lack of knowledge of recent evolution of each H1N1 viral gene segment precludes the use of this approach to determine viral origins. CONCLUSIONS/SIGNIFICANCE: We conclude that strategies to prevent pandemic influenza virus emergence and spread in the future should include: 1) enhanced surveillance for strains resulting from reassortment in traded livestock; 2) rapid deployment of control measures in the initial spreading phase to countries where travel data predict the pathogen will reach and to countries where lower healthcare resources will likely cause delays in reporting. Our results highlight the benefits, for all parties, when higher income countries provide additional healthcare resources for lower income countries, particularly those that have high air traffic volumes. In particular, international authorities should prioritize aid to those poorest countries where both the risk of emerging infectious diseases and air traffic volume is highest. This strategy will result in earlier detection of pathogens and a reduction in the impact of future pandemics.",2010 Sep 15,"['Hosseini, Parviez', 'Sokolow, Susanne H.', 'Vandegrift, Kurt J.', 'Kilpatrick, A. Marm', 'Daszak, Peter']",PLoS One,,,False
d7a0bbfc13566c612f060bab06c96edf195be539,PMC,Predictive Power of Air Travel and Socio-Economic Data for Early Pandemic Spread,http://dx.doi.org/10.1371/journal.pone.0012763,PMC2939898,20856678,CC BY,"BACKGROUND: Controlling the pandemic spread of newly emerging diseases requires rapid, targeted allocation of limited resources among nations. Critical, early control steps would be greatly enhanced if the key risk factors can be identified that accurately predict early disease spread immediately after emergence. METHODOLOGY/PRINCIPAL FINDINGS: Here, we examine the role of travel, trade, and national healthcare resources in predicting the emergence and initial spread of 2009 A/H1N1 influenza. We find that incorporating national healthcare resource data into our analyses allowed a much greater capacity to predict the international spread of this virus. In countries with lower healthcare resources, the reporting of 2009 A/H1N1 cases was significantly delayed, likely reflecting a lower capacity for testing and reporting, as well as other socio-political issues. We also report substantial international trade in live swine and poultry in the decade preceding the pandemic which may have contributed to the emergence and mixed genotype of this pandemic strain. However, the lack of knowledge of recent evolution of each H1N1 viral gene segment precludes the use of this approach to determine viral origins. CONCLUSIONS/SIGNIFICANCE: We conclude that strategies to prevent pandemic influenza virus emergence and spread in the future should include: 1) enhanced surveillance for strains resulting from reassortment in traded livestock; 2) rapid deployment of control measures in the initial spreading phase to countries where travel data predict the pathogen will reach and to countries where lower healthcare resources will likely cause delays in reporting. Our results highlight the benefits, for all parties, when higher income countries provide additional healthcare resources for lower income countries, particularly those that have high air traffic volumes. In particular, international authorities should prioritize aid to those poorest countries where both the risk of emerging infectious diseases and air traffic volume is highest. This strategy will result in earlier detection of pathogens and a reduction in the impact of future pandemics.",2010 Sep 15,"['Hosseini, Parviez', 'Sokolow, Susanne H.', 'Vandegrift, Kurt J.', 'Kilpatrick, A. Marm', 'Daszak, Peter']",PLoS One,,,False
c73aa8452ccd63758df52737aae67450f078e76b,PMC,The N-Terminal Domain of the Arenavirus L Protein Is an RNA Endonuclease Essential in mRNA Transcription,http://dx.doi.org/10.1371/journal.ppat.1001038,PMC2940758,20862324,CC BY,"Arenaviridae synthesize viral mRNAs using short capped primers presumably acquired from cellular transcripts by a ‘cap-snatching’ mechanism. Here, we report the crystal structure and functional characterization of the N-terminal 196 residues (NL1) of the L protein from the prototypic arenavirus: lymphocytic choriomeningitis virus. The NL1 domain is able to bind and cleave RNA. The 2.13 Å resolution crystal structure of NL1 reveals a type II endonuclease α/β architecture similar to the N-terminal end of the influenza virus PA protein. Superimposition of both structures, mutagenesis and reverse genetics studies reveal a unique spatial arrangement of key active site residues related to the PD…(D/E)XK type II endonuclease signature sequence. We show that this endonuclease domain is conserved and active across the virus families Arenaviridae, Bunyaviridae and Orthomyxoviridae and propose that the arenavirus NL1 domain is the Arenaviridae cap-snatching endonuclease.",2010 Sep 16,"['Morin, Benjamin', 'Coutard, Bruno', 'Lelke, Michaela', 'Ferron, François', 'Kerber, Romy', 'Jamal, Saïd', 'Frangeul, Antoine', 'Baronti, Cécile', 'Charrel, Rémi', 'de Lamballerie, Xavier', 'Vonrhein, Clemens', 'Lescar, Julien', 'Bricogne, Gérard', 'Günther, Stephan', 'Canard, Bruno']",PLoS Pathog,,,True
d7e90855b317646bba5751946a9a5e675ea90fdc,PMC,"Hospitalized adult patients with 2009 influenza A(H1N1) in Beijing, China: risk factors for hospital mortality",http://dx.doi.org/10.1186/1471-2334-10-256,PMC2941683,20799934,CC BY,"BACKGROUND: In April 2009, the pandemic influenza A(H1N1) virus emerged and spread globally. The objective of this study was to describe the independent risk factors for hospital mortality and the treatment effect of corticosteroids among patients with 2009 influenza A(H1N1) infection. METHODS: We retrospectively obtained clinical data of 155 adult patients with confirmed infection of 2009 influenza A(H1N1) in 23 hospitals in Beijing, China from October 1 to December 23, 2009. Risk factors for hospital mortality were identified with multivariate logistic regression analysis. RESULTS: Among the 155 patients, 90 (58.1%) were male, and mean age was 43.0 ± 18.6 years, and comorbidities were present in 81 (52.3%) patients. The most common organ dysfunctions included acute respiratory failure, altered mental status, septic shock, and acute renal failure. Oseltamivir was initiated in 125 patients (80.6%), only 16 patients received antiviral therapy within 48 hours after symptom onset. Fifty-two patients (33.5%) were treated with systemic corticosteroids, with a median daily dose of 80 mg. Twenty-seven patients (17.4%) died during hospital stay. Diabetes [odds ratio (OR) 8.830, 95% confidence interval [CI] 2.041 to 38.201, p = 0.004) and lactate dehydrogenase (LDH) level (OR 1.240, 95% CI 1.025 to 1.500, p = 0.027) were independent risk factors of hospital death, as were septic shock and altered mental status. Corticosteroids use was associated with a trend toward higher hospital mortality (OR 3.668, 95% CI 0.987 to 13.640, p = 0.052). CONCLUSIONS: Hospitalized patients with 2009 H1N1 influenza had relative poor outcome. The risk factors at hospitalization may help clinicians to identify the high-risk patients. In addition, corticosteroids use should not be regarded as routine pharmacologic therapy.",2010 Aug 27,"['Xi, Xiuming', 'Xu, Yuan', 'Jiang, Li', 'Li, Ang', 'Duan, Jie', 'Du, Bin']",BMC Infect Dis,,,True
8a0731d1284b815e6139b1a40a4cc1f3b68dd4f3,PMC,Genome3D: A viewer-model framework for integrating and visualizing multi-scale epigenomic information within a three-dimensional genome,http://dx.doi.org/10.1186/1471-2105-11-444,PMC2941692,20813045,CC BY,"BACKGROUND: New technologies are enabling the measurement of many types of genomic and epigenomic information at scales ranging from the atomic to nuclear. Much of this new data is increasingly structural in nature, and is often difficult to coordinate with other data sets. There is a legitimate need for integrating and visualizing these disparate data sets to reveal structural relationships not apparent when looking at these data in isolation. RESULTS: We have applied object-oriented technology to develop a downloadable visualization tool, Genome3D, for integrating and displaying epigenomic data within a prescribed three-dimensional physical model of the human genome. In order to integrate and visualize large volume of data, novel statistical and mathematical approaches have been developed to reduce the size of the data. To our knowledge, this is the first such tool developed that can visualize human genome in three-dimension. We describe here the major features of Genome3D and discuss our multi-scale data framework using a representative basic physical model. We then demonstrate many of the issues and benefits of multi-resolution data integration. CONCLUSIONS: Genome3D is a software visualization tool that explores a wide range of structural genomic and epigenetic data. Data from various sources of differing scales can be integrated within a hierarchical framework that is easily adapted to new developments concerning the structure of the physical genome. In addition, our tool has a simple annotation mechanism to incorporate non-structural information. Genome3D is unique is its ability to manipulate large amounts of multi-resolution data from diverse sources to uncover complex and new structural relationships within the genome.",2010 Sep 2,"['Asbury, Thomas M', 'Mitman, Matt', 'Tang, Jijun', 'Zheng, W Jim']",BMC Bioinformatics,,,True
1d14fd3be698da4aa12b91523c9d099f76775604,PMC,Modulation of polymorphonuclear neutrophil functions by astrocytes,http://dx.doi.org/10.1186/1742-2094-7-53,PMC2942816,20828397,CC BY,"BACKGROUND: Neuroinflammation is a complex process involving cells from the immune system and the central nerve system (CNS). Polymorphonuclear neutrophils (PMN) are the most abundant class of white blood cells, and typically the first type of leukocyte recruited to sites of inflammation. In the CNS, astrocytes are the most abundant glial cell population and participate in the local innate immune response triggered by a variety of insults. In the present study, we investigated the impacts of astrocytes on PMN function. METHODS: Primary astrocyte cultures were derived from postnatal C57BL/6 mice and primary neutrophils were isolated from 8 to 12 weeks old C57BL/6 mice. PMNs respiratory burst was analyzed by H2DCFDA assay. For phagocytosis assay, neutrophils were incubated with FITC-labeled E. coli and the phagocytosis of E coli was determined by flow cytometer. PMNs degranulation was determined by myeloperoxidase assay. Cytokine expression was determined by real-time PCR. To determine the involvement of different signaling pathway, protein lysates were prepared and western blots were conducted to assess the activation of Akt, Erk1/2, and p38. RESULTS: Using ex vivo neutrophils and primary astrocyte cultures, our study demonstrated that astrocytes differentially regulate neutrophil functions, depending upon whether the interactions between the two cell types are direct or indirect. Upon direct cell-cell contact, astrocytes attenuate neutrophil apoptosis, respiratory bust, and degranulation, while enhancing neutrophil phagocytic capability and pro-inflammatory cytokine expression. Through indirect interaction with neutrophils, astrocytes attenuate apoptosis and enhance necrosis in neutrophils, augment neutrophil phagocytosis and respiratory burst, and inhibit neutrophil degranulation. In addition, astrocytes could augment Akt, Erk1/2, and p38 activation in neutrophils. CONCLUSIONS: Astrocytes differentially regulate neutrophil functions through direct or indirect interactions between the two cell types. The diversified actions of astrocytes on neutrophils might provide protection against potential microbial infections given compromised blood-brain barrier integrity under certain neuropathological conditions. The complex actions of astrocytes on neutrophils could provide further insight to harness the inflammatory response to promote CNS repair.",2010 Sep 9,"['Xie, Luokun', 'Poteet, Ethan C', 'Li, Wenjun', 'Scott, Amanda E', 'Liu, Ran', 'Wen, Yi', 'Ghorpade, Anuja', 'Simpkins, James W', 'Yang, Shao-Hua']",J Neuroinflammation,,,True
1c363c20418dda4f6c674f6d7af16f92b5dce974,PMC,Q&A: Antibiotic resistance: where does it come from and what can we do about it?,http://dx.doi.org/10.1186/1741-7007-8-123,PMC2942819,20887638,CC BY,,2010 Sep 20,"Wright, Gerard D",BMC Biol,,,True
59e3592ad1516fe1b4f4a1ea5a8cae320af5cf7d,PMC,"VIGOR, an annotation program for small viral genomes",http://dx.doi.org/10.1186/1471-2105-11-451,PMC2942859,20822531,CC BY,"BACKGROUND: The decrease in cost for sequencing and improvement in technologies has made it easier and more common for the re-sequencing of large genomes as well as parallel sequencing of small genomes. It is possible to completely sequence a small genome within days and this increases the number of publicly available genomes. Among the types of genomes being rapidly sequenced are those of microbial and viral genomes responsible for infectious diseases. However, accurate gene prediction is a challenge that persists for decoding a newly sequenced genome. Therefore, accurate and efficient gene prediction programs are highly desired for rapid and cost effective surveillance of RNA viruses through full genome sequencing. RESULTS: We have developed VIGOR (Viral Genome ORF Reader), a web application tool for gene prediction in influenza virus, rotavirus, rhinovirus and coronavirus subtypes. VIGOR detects protein coding regions based on sequence similarity searches and can accurately detect genome specific features such as frame shifts, overlapping genes, embedded genes, and can predict mature peptides within the context of a single polypeptide open reading frame. Genotyping capability for influenza and rotavirus is built into the program. We compared VIGOR to previously described gene prediction programs, ZCURVE_V, GeneMarkS and FLAN. The specificity and sensitivity of VIGOR are greater than 99% for the RNA viral genomes tested. CONCLUSIONS: VIGOR is a user friendly web-based genome annotation program for five different viral agents, influenza, rotavirus, rhinovirus, coronavirus and SARS coronavirus. This is the first gene prediction program for rotavirus and rhinovirus for public access. VIGOR is able to accurately predict protein coding genes for the above five viral types and has the capability to assign function to the predicted open reading frames and genotype influenza virus. The prediction software was designed for performing high throughput annotation and closure validation in a post-sequencing production pipeline.",2010 Sep 7,"['Wang, Shiliang', 'Sundaram, Jaideep P', 'Spiro, David']",BMC Bioinformatics,,,True
0ce2f11a7c4da992b9a8686bd3b2ed53064a2ac8,PMC,Ambient Influenza and Avian Influenza Virus during Dust Storm Days and Background Days,http://dx.doi.org/10.1289/ehp.0901782,PMC2944079,20435545,CC0,"BACKGROUND: The spread of influenza and highly pathogenic avian influenza (H5N1) presents a significant threat to human health. Avian influenza outbreaks in downwind areas of Asian dust storms (ADS) suggest that viruses might be transported by dust storms. OBJECTIVES: We developed a technique to measure ambient influenza and avian influenza viruses. We then used this technique to measure concentrations of these viruses on ADS days and background days, and to assess the relationships between ambient influenza and avian influenza viruses, and air pollutants. METHODS: A high-volume air sampler was used in parallel with a filter cassette to evaluate spiked samples and unspiked samples. Then, air samples were monitored during ADS seasons using a filter cassette coupled with a real-time quantitative polymerase chain reaction (qPCR) assay. Air samples were monitored during ADS season (1 January to 31 May 2006). RESULTS: We successfully quantified ambient influenza virus using the filtration/real-time qPCR method during ADS days and background days. To our knowledge, this is the first report describing the concentration of influenza virus in ambient air. In both the spiked and unspiked samples, the concentration of influenza virus sampled using the filter cassette was higher than that using the high-volume sampler. The concentration of ambient influenza A virus was significantly higher during the ADS days than during the background days. CONCLUSIONS: Our data imply the possibility of long-range transport of influenza virus.",2010 Sep 30,"['Chen, Pei-Shih', 'Tsai, Feng Ta', 'Lin, Chien Kun', 'Yang, Chun-Yuh', 'Chan, Chang-Chuan', 'Young, Chea-Yuan', 'Lee, Chien-Hung']",Environ Health Perspect,,,True
a776acb66d26bc9ad550cb9909e0f1ef35b57fec,PMC,Phylogenetic history demonstrates two different lineages of dengue type 1 virus in Colombia,http://dx.doi.org/10.1186/1743-422X-7-226,PMC2944171,20836894,CC BY,"BACKGROUND: Dengue Fever is one of the most important viral re-emergent diseases affecting about 50 million people around the world especially in tropical and sub-tropical countries. In Colombia, the virus was first detected in the earliest 70's when the disease became a major public health concern. Since then, all four serotypes of the virus have been reported. Although most of the huge outbreaks reported in this country have involved dengue virus serotype 1 (DENV-1), there are not studies about its origin, genetic diversity and distribution. RESULTS: We used 224 bp corresponding to the carboxyl terminus of envelope (E) gene from 74 Colombian isolates in order to reconstruct phylogenetic relationships and to estimate time divergences. Analyzed DENV-1 Colombian isolates belonged to the formerly defined genotype V. Only one virus isolate was clasified in the genotype I, likely representing a sole introduction that did not spread. The oldest strains were closely related to those detected for the first time in America in 1977 from the Caribbean and were detected for two years until their disappearance about six years later. Around 1987, a split up generated 2 lineages that have been evolving separately, although not major aminoacid changes in the analyzed region were found. CONCLUSION: DENV-1 has been circulating since 1978 in Colombia. Yet, the phylogenetic relationships between strains isolated along the covered period of time suggests that viral strains detected in some years, although belonging to the same genotype V, have different recent origins corresponding to multiple re-introduction events of viral strains that were circulating in neighbor countries. Viral strains used in the present study did not form a monophyletic group, which is evidence of a polyphyletic origin. We report the rapid spread patterns and high evolution rate of the different DENV-1 lineages.",2010 Sep 14,"['Mendez, Jairo A', 'Usme-Ciro, Jose A', 'Domingo, Cristina', 'Rey, Gloria J', 'Sanchez, Juan A', 'Tenorio, Antonio', 'Gallego-Gomez, Juan C']",Virol J,,,True
ac14252dbac614e01fef29b981cd841aa223f28e,PMC,Sequential introduction of single room isolation and hand hygiene campaign in the control of methicillin-resistant Staphylococcus aureus in intensive care unit,http://dx.doi.org/10.1186/1471-2334-10-263,PMC2944349,20822509,CC BY,"BACKGROUND: After renovation of the adult intensive care unit (ICU) with installation of ten single rooms, an enhanced infection control program was conducted to control the spread of methicillin-resistant Staphylococcus aureus (MRSA) in our hospital. METHODS: Since the ICU renovation, all patients colonized or infected with MRSA were nursed in single rooms with contact precautions. The incidence of MRSA infection in the ICU was monitored during 3 different phases: the baseline period (phase 1); after ICU renovation (phase 2) and after implementation of a hand hygiene campaign with alcohol-based hand rub (phase 3). Patients infected with extended spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella species were chosen as controls because they were managed in open cubicles with standard precautions. RESULTS: Without a major change in bed occupancy rate, nursing workforce, or the protocol of environmental cleansing throughout the study period, a stepwise reduction in ICU onset nonbacteraemic MRSA infection was observed: from 3.54 (phase 1) to 2.26 (phase 2, p = 0.042) and 1.02 (phase 3, p = 0.006) per 1000-patient-days. ICU onset bacteraemic MRSA infection was significantly reduced from 1.94 (phase 1) to 0.9 (phase 2, p = 0.005) and 0.28 (phase 3, p = 0.021) per 1000-patient-days. Infection due to ESBL-producing organisms did not show a corresponding reduction. The usage density of broad-spectrum antibiotics and fluoroquinolones increased from phase 1 to 3. However a significant trend improvement of ICU onset MRSA infection by segmented regression analysis can only be demonstrated when comparison was made before and after the severe acute respiratory syndrome (SARS) epidemic. This suggests that the deaths of fellow healthcare workers from an occupational acquired infection had an overwhelming effect on their compliance with infection control measures. CONCLUSION: Provision of single room isolation facilities and promotion of hand hygiene practice are important. However compliance with infection control measures relies largely on a personal commitment, which may increase when personal safety is threatened.",2010 Sep 7,"['Cheng, Vincent CC', 'Tai, Josepha WM', 'Chan, WM', 'Lau, Eric HY', 'Chan, Jasper FW', 'To, Kelvin KW', 'Li, Iris WS', 'Ho, PL', 'Yuen, KY']",BMC Infect Dis,,,True
e077bb756a7a9e4df0cdcc18f2e1cd509e4a3993,PMC,Evolutionary Entropy Determines Invasion Success in Emergent Epidemics,http://dx.doi.org/10.1371/journal.pone.0012951,PMC2944876,20886082,CC BY,"BACKGROUND: Standard epidemiological theory claims that in structured populations competition between multiple pathogen strains is a deterministic process which is mediated by the basic reproduction number ([Image: see text]) of the individual strains. A new theory based on analysis, simulation and empirical study challenges this predictor of success. PRINCIPAL FINDINGS: We show that the quantity [Image: see text] is a valid predictor in structured populations only when size is infinite. In this article we show that when population size is finite the dynamics of infection by multi-strain pathogens is a stochastic process whose outcome can be predicted by evolutionary entropy, S, an information theoretic measure which describes the uncertainty in the infectious age of an infected parent of a randomly chosen new infective. Evolutionary entropy characterises the demographic stability or robustness of the population of infectives. This statistical parameter determines the duration of infection and thus provides a quantitative index of the pathogenicity of a strain. Standard epidemiological theory based on [Image: see text] as a measure of selective advantage is the limit as the population size tends to infinity of the entropic selection theory. The standard model is an approximation to the entropic selection theory whose validity increases with population size. CONCLUSION: An epidemiological analysis based on entropy is shown to explain empirical observations regarding the emergence of less pathogenic strains of human influenza during the antigenic drift phase. Furthermore, we exploit the entropy perspective to discuss certain epidemiological patterns of the current H1N1 swine 'flu outbreak.",2010 Sep 23,"['Rhodes, Christopher J.', 'Demetrius, Lloyd']",PLoS One,,,True
a25045aa52c78b89840287b2cff9d7dffe0bb07f,PMC,The Nature of Protein Domain Evolution: Shaping the Interaction Network,http://dx.doi.org/10.2174/138920210791616725,PMC2945003,21286315,CC BY,"The proteomes that make up the collection of proteins in contemporary organisms evolved through recombination and duplication of a limited set of domains. These protein domains are essentially the main components of globular proteins and are the most principal level at which protein function and protein interactions can be understood. An important aspect of domain evolution is their atomic structure and biochemical function, which are both specified by the information in the amino acid sequence. Changes in this information may bring about new folds, functions and protein architectures. With the present and still increasing wealth of sequences and annotation data brought about by genomics, new evolutionary relationships are constantly being revealed, unknown structures modeled and phylogenies inferred. Such investigations not only help predict the function of newly discovered proteins, but also assist in mapping unforeseen pathways of evolution and reveal crucial, co-evolving inter- and intra-molecular interactions. In turn this will help us describe how protein domains shaped cellular interaction networks and the dynamics with which they are regulated in the cell. Additionally, these studies can be used for the design of new and optimized protein domains for therapy. In this review, we aim to describe the basic concepts of protein domain evolution and illustrate recent developments in molecular evolution that have provided valuable new insights in the field of comparative genomics and protein interaction networks.",2010 Aug,"['Bagowski, Christoph P', 'Bruins, Wouter', 'te Velthuis, Aartjan J.W']",Curr Genomics,,,True
9752210c4ae3a172559d5d7b3df9575e26b7359c,PMC,Pandemic influenza control in Europe and the constraints resulting from incoherent public health laws,http://dx.doi.org/10.1186/1471-2458-10-532,PMC2945945,20815888,CC BY,"BACKGROUND: With the emergence of influenza H1N1v the world is facing its first 21(st )century global pandemic. Severe Acute Respiratory Syndrome (SARS) and avian influenza H5N1 prompted development of pandemic preparedness plans. National systems of public health law are essential for public health stewardship and for the implementation of public health policy[1]. International coherence will contribute to effective regional and global responses. However little research has been undertaken on how law works as a tool for disease control in Europe. With co-funding from the European Union, we investigated the extent to which laws across Europe support or constrain pandemic preparedness planning, and whether national differences are likely to constrain control efforts. METHODS: We undertook a survey of national public health laws across 32 European states using a questionnaire designed around a disease scenario based on pandemic influenza. Questionnaire results were reviewed in workshops, analysing how differences between national laws might support or hinder regional responses to pandemic influenza. Respondents examined the impact of national laws on the movements of information, goods, services and people across borders in a time of pandemic, the capacity for surveillance, case detection, case management and community control, the deployment of strategies of prevention, containment, mitigation and recovery and the identification of commonalities and disconnects across states. RESULTS: Results of this study show differences across Europe in the extent to which national pandemic policy and pandemic plans have been integrated with public health laws. We found significant differences in legislation and in the legitimacy of strategic plans. States differ in the range and the nature of intervention measures authorized by law, the extent to which borders could be closed to movement of persons and goods during a pandemic, and access to healthcare of non-resident persons. Some states propose use of emergency powers that might potentially override human rights protections while other states propose to limit interventions to those authorized by public health laws. CONCLUSION: These differences could create problems for European strategies if an evolving influenza pandemic results in more serious public health challenges or, indeed, if a novel disease other than influenza emerges with pandemic potential. There is insufficient understanding across Europe of the role and importance of law in pandemic planning. States need to build capacity in public health law to support disease prevention and control policies. Our research suggests that states would welcome further guidance from the EU on management of a pandemic, and guidance to assist in greater commonality of legal approaches across states.",2010 Sep 3,"['Martin, Robyn', 'Conseil, Alexandra', 'Longstaff, Abie', 'Kodo, Jimmy', 'Siegert, Joachim', 'Duguet, Anne-Marie', 'Lobato de Faria, Paula', 'Haringhuizen, George', 'Espin, Jaime', 'Coker, Richard']",BMC Public Health,,,True
9fb2d27c92ebc1fc7804e55e557fe8c126da62f9,PMC,Respiratory Syncytial Virus (RSV) RNA loads in peripheral blood correlates with disease severity in mice,http://dx.doi.org/10.1186/1465-9921-11-125,PMC2946301,20843364,CC BY,"BACKGROUND: Respiratory Syncytial Virus (RSV) infection is usually restricted to the respiratory epithelium. Few studies have documented the presence of RSV in the systemic circulation, however there is no consistent information whether virus detection in the blood correlates with disease severity. METHODS: Balb/c mice were inoculated with live RSV, heat-inactivated RSV or medium. A subset of RSV-infected mice was treated with anti-RSV antibody 72 h post-inoculation. RSV RNA loads were measured by PCR in peripheral blood from day 1-21 post-inoculation and were correlated with upper and lower respiratory tract viral loads, the systemic cytokine response, lung inflammation and pulmonary function. Immunohistochemical staining was used to define the localization of RSV antigens in the respiratory tract and peripheral blood. RESULTS: RSV RNA loads were detected in peripheral blood from day 1 to 14 post-inoculation, peaked on day 5 and significantly correlated with nasal and lung RSV loads, airway obstruction, and blood CCL2 and CXCL1 expression. Treatment with anti-RSV antibody reduced blood RSV RNA loads and improved airway obstruction. Immunostaining identified RSV antigens in alveolar macrophages and peripheral blood monocytes. CONCLUSIONS: RSV RNA was detected in peripheral blood upon infection with live RSV, followed a time-course parallel to viral loads assessed in the respiratory tract and was significantly correlated with RSV-induced airway disease.",2010 Sep 15,"['Torres, Juan Pablo', 'Gomez, Ana M', 'Khokhar, Shama', 'Bhoj, Vijay G', 'Tagliabue, Claudia', 'Chang, Michael L', 'Kiener, Peter A', 'Revell, Paula A', 'Ramilo, Octavio', 'Mejias, Asuncion']",Respir Res,,,True
e45e16034a3ab42bfce64e2b6886604a57974091,PMC,Quantitative Phosphoproteomics of Proteasome Inhibition in Multiple Myeloma Cells,http://dx.doi.org/10.1371/journal.pone.0013095,PMC2947515,20927383,CC BY,"BACKGROUND: The proteasome inhibitor bortezomib represents an important advance in the treatment of multiple myeloma (MM). Bortezomib inhibits the activity of the 26S proteasome and induces cell death in a variety of tumor cells; however, the mechanism of cytotoxicity is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the differential phosphoproteome upon proteasome inhibition by using stable isotope labeling by amino acids in cell culture (SILAC) in combination with phosphoprotein enrichment and LC-MS/MS analysis. In total 233 phosphoproteins were identified and 72 phosphoproteins showed a 1.5-fold or greater change upon bortezomib treatment. The phosphoproteins with expression alterations encompass all major protein classes, including a large number of nucleic acid binding proteins. Site-specific phosphopeptide quantitation revealed that Ser38 phosphorylation on stathmin increased upon bortezomib treatment, suggesting new mechanisms associated to bortezomib-induced apoptosis in MM cells. Further studies demonstrated that stathmin phosphorylation profile was modified in response to bortezomib treatment and the regulation of stathmin by phosphorylation at specific Ser/Thr residues participated in the cellular response induced by bortezomib. CONCLUSIONS/SIGNIFICANCE: Our systematic profiling of phosphorylation changes in response to bortezomib treatment not only advanced the global mechanistic understanding of the action of bortezomib on myeloma cells but also identified previously uncharacterized signaling proteins in myeloma cells.",2010 Sep 29,"['Ge, Feng', 'Xiao, Chuan-Le', 'Bi, Li-Jun', 'Tao, Sheng-Ce', 'Xiong, Sheng', 'Yin, Xin-Feng', 'Li, Li-Ping', 'Lu, Chun-Hua', 'Jia, Hai-Tao', 'He, Qing-Yu']",PLoS One,,,True
303dd57924047b30670081699eb8c991bf0f41b5,PMC,Insights into the Evolution and Emergence of a Novel Infectious Disease,http://dx.doi.org/10.1371/journal.pcbi.1000947,PMC2947978,20941384,CC BY,"Many zoonotic, novel infectious diseases in humans appear as sporadic infections with spatially and temporally restricted outbreaks, as seen with influenza A(H5N1). Adaptation is often a key factor for successfully establishing sustained human-to-human transmission. Here we use simple mathematical models to describe different adaptation scenarios with particular reference to spatial heterogeneity within the human population. We present analytical expressions for the probability of emergence per introduction, as well as the waiting time to a successful emergence event. Furthermore, we derive general analytical results for the statistical properties of emergence events, including the probability distribution of outbreak sizes. We compare our analytical results with a stochastic model, which has previously been studied computationally. Our results suggest that, for typical connection strengths between communities, spatial heterogeneity has only a weak effect on outbreak size distributions, and on the risk of emergence per introduction. For example, if [Image: see text] or larger, any village connected to a large city by just ten commuters a day is, effectively, just a part of the city when considering the chances of emergence and the outbreak size distribution. We present empirical data on commuting patterns and show that the vast majority of communities for which such data are available are at least this well interconnected. For plausible parameter ranges, the effects of spatial heterogeneity are likely to be dominated by the evolutionary biology of host adaptation. We conclude by discussing implications for surveillance and control of emerging infections.",2010 Sep 30,"['Kubiak, Ruben J.', 'Arinaminpathy, Nimalan', 'McLean, Angela R.']",PLoS Comput Biol,,,True
41fe2339a1ad28cdcaff3e45b41c4cbd05a0b163,PMC,Insights into the Evolution and Emergence of a Novel Infectious Disease,http://dx.doi.org/10.1371/journal.pcbi.1000947,PMC2947978,20941384,CC BY,"Many zoonotic, novel infectious diseases in humans appear as sporadic infections with spatially and temporally restricted outbreaks, as seen with influenza A(H5N1). Adaptation is often a key factor for successfully establishing sustained human-to-human transmission. Here we use simple mathematical models to describe different adaptation scenarios with particular reference to spatial heterogeneity within the human population. We present analytical expressions for the probability of emergence per introduction, as well as the waiting time to a successful emergence event. Furthermore, we derive general analytical results for the statistical properties of emergence events, including the probability distribution of outbreak sizes. We compare our analytical results with a stochastic model, which has previously been studied computationally. Our results suggest that, for typical connection strengths between communities, spatial heterogeneity has only a weak effect on outbreak size distributions, and on the risk of emergence per introduction. For example, if [Image: see text] or larger, any village connected to a large city by just ten commuters a day is, effectively, just a part of the city when considering the chances of emergence and the outbreak size distribution. We present empirical data on commuting patterns and show that the vast majority of communities for which such data are available are at least this well interconnected. For plausible parameter ranges, the effects of spatial heterogeneity are likely to be dominated by the evolutionary biology of host adaptation. We conclude by discussing implications for surveillance and control of emerging infections.",2010 Sep 30,"['Kubiak, Ruben J.', 'Arinaminpathy, Nimalan', 'McLean, Angela R.']",PLoS Comput Biol,,,False
50e55ab8dd87f7523b7f25203ef10004c8d3b13e,PMC,Role of Host Immune Response and Viral Load in the Differential Outcome of Pandemic H1N1 (2009) Influenza Virus Infection in Indian Patients,http://dx.doi.org/10.1371/journal.pone.0013099,PMC2948498,20957032,CC BY,"BACKGROUND: An unusually high number of severe pneumonia cases with considerable mortality is being observed with the pandemic H1N1 2009 virus infections globally. In India, all mild as well as critically ill cases were admitted and treated in the government hospitals during the initial phase of the pandemic. The present study was undertaken during this early phase of the pandemic. METHODOLOGY: The role of viral load and host factors in the pathogenesis were assessed by examining 26 mild (MP), 15 critically ill patients (CIP) and 20 healthy controls from Pune, India. Sequential blood and lung aspirate samples were collected from CIP. Viral load and cytokines/chemokine levels were determined from the plasma and lung aspirates of the patients. TLR levels were determined by staining and FACS analysis. Gene profiling was done for both cells in the lung aspirates and PBMCs using TaqMan Low Density arrays. Antibody titres and isotyping was done using HA protein based ELISAs. PRINCIPAL FINDINGS: 13/15 critically ill patients expired. All plasma samples were negative for the virus irrespective of the patient's category. Sequential lung samples from CIP showed lower viral loads questioning association of viral replication with the severity. Anti-rpH1N1-09-HA-IgG titres were significantly higher in critically ill patients and both categories circulated exclusively IgG1 isotype. Critically ill patients exhibited increase in TLR-3, 4, 7 and decrease in TLR-2 expressions. The disease severity correlated with increased plasma levels of IL1RA, IL2, IL6, CCL3, CCL4 and IL10. Majority of the immune-function genes were down-regulated in the PBMCs and up-regulated in the cells from lung aspirates of critically ill patients. No distinct pattern differentiating fatal and surviving patients was observed when sequential samples were examined for various parameters. CONCLUSIONS: Disease severity was associated with pronounced impairment of host immune response.",2010 Oct 1,"['Arankalle, Vidya A.', 'Lole, Kavita S.', 'Arya, Ravi P.', 'Tripathy, Anuradha S.', 'Ramdasi, Ashwini Y.', 'Chadha, Mandeep S.', 'Sangle, Shashi A.', 'Kadam, Deelip B.']",PLoS One,,,True
69a50ad03d5fb9a5129663062a9b718217b62665,PMC,Generation of Human Antigen-Specific Monoclonal IgM Antibodies Using Vaccinated “Human Immune System” Mice,http://dx.doi.org/10.1371/journal.pone.0013137,PMC2949385,20957227,CC BY,"BACKGROUND: Passive transfer of antibodies not only provides immediate short-term protection against disease, but also can be exploited as a therapeutic tool. However, the ‘humanization’ of murine monoclonal antibodies (mAbs) is a time-consuming and expensive process that has the inherent drawback of potentially altering antigenic specificity and/or affinity. The immortalization of human B cells represents an alternative for obtaining human mAbs, but relies on the availability of biological samples from vaccinated individuals or convalescent patients. In this work we describe a novel approach to generate fully human mAbs by combining a humanized mouse model with a new B cell immortalization technique. METHODOLOGY/PRINCIPAL FINDINGS: After transplantation with CD34(+)CD38(−) human hematopoietic progenitor cells, BALB/c Rag2(−/−)IL-2Rγc(−/−) mice acquire a human immune system and harbor B cells with a diverse IgM repertoire. “Human Immune System” mice were then immunized with two commercial vaccine antigens, tetanus toxoid and hepatitis B surface antigen. Sorted human CD19(+)CD27(+) B cells were retrovirally transduced with the human B cell lymphoma (BCL)-6 and BCL-XL genes, and subsequently cultured in the presence of CD40-ligand and IL-21. This procedure allows generating stable B cell receptor-positive B cells that secrete immunoglobulins. We recovered stable B cell clones that produced IgM specific for tetanus toxoid and the hepatitis B surface antigen, respectively. CONCLUSION/SIGNIFICANCE: This work provides the proof-of-concept for the usefulness of this novel method based on the immunization of humanized mice for the rapid generation of human mAbs against a wide range of antigens.",2010 Oct 4,"['Becker, Pablo D.', 'Legrand, Nicolas', 'van Geelen, Caroline M. M.', 'Noerder, Miriam', 'Huntington, Nicholas D.', 'Lim, Annick', 'Yasuda, Etsuko', 'Diehl, Sean A.', 'Scheeren, Ferenc A.', 'Ott, Michael', 'Weijer, Kees', 'Wedemeyer, Heiner', 'Di Santo, James P.', 'Beaumont, Tim', 'Guzman, Carlos A.', 'Spits, Hergen']",PLoS One,,,True
bde7fe0594a0902867cbde6e9271090f7f5fe9ac,PMC,Generation of Human Antigen-Specific Monoclonal IgM Antibodies Using Vaccinated “Human Immune System” Mice,http://dx.doi.org/10.1371/journal.pone.0013137,PMC2949385,20957227,CC BY,"BACKGROUND: Passive transfer of antibodies not only provides immediate short-term protection against disease, but also can be exploited as a therapeutic tool. However, the ‘humanization’ of murine monoclonal antibodies (mAbs) is a time-consuming and expensive process that has the inherent drawback of potentially altering antigenic specificity and/or affinity. The immortalization of human B cells represents an alternative for obtaining human mAbs, but relies on the availability of biological samples from vaccinated individuals or convalescent patients. In this work we describe a novel approach to generate fully human mAbs by combining a humanized mouse model with a new B cell immortalization technique. METHODOLOGY/PRINCIPAL FINDINGS: After transplantation with CD34(+)CD38(−) human hematopoietic progenitor cells, BALB/c Rag2(−/−)IL-2Rγc(−/−) mice acquire a human immune system and harbor B cells with a diverse IgM repertoire. “Human Immune System” mice were then immunized with two commercial vaccine antigens, tetanus toxoid and hepatitis B surface antigen. Sorted human CD19(+)CD27(+) B cells were retrovirally transduced with the human B cell lymphoma (BCL)-6 and BCL-XL genes, and subsequently cultured in the presence of CD40-ligand and IL-21. This procedure allows generating stable B cell receptor-positive B cells that secrete immunoglobulins. We recovered stable B cell clones that produced IgM specific for tetanus toxoid and the hepatitis B surface antigen, respectively. CONCLUSION/SIGNIFICANCE: This work provides the proof-of-concept for the usefulness of this novel method based on the immunization of humanized mice for the rapid generation of human mAbs against a wide range of antigens.",2010 Oct 4,"['Becker, Pablo D.', 'Legrand, Nicolas', 'van Geelen, Caroline M. M.', 'Noerder, Miriam', 'Huntington, Nicholas D.', 'Lim, Annick', 'Yasuda, Etsuko', 'Diehl, Sean A.', 'Scheeren, Ferenc A.', 'Ott, Michael', 'Weijer, Kees', 'Wedemeyer, Heiner', 'Di Santo, James P.', 'Beaumont, Tim', 'Guzman, Carlos A.', 'Spits, Hergen']",PLoS One,,,False
51bc480cd0248cb14486d0c20a6693b032fd8043,PMC,Generation of Human Antigen-Specific Monoclonal IgM Antibodies Using Vaccinated “Human Immune System” Mice,http://dx.doi.org/10.1371/journal.pone.0013137,PMC2949385,20957227,CC BY,"BACKGROUND: Passive transfer of antibodies not only provides immediate short-term protection against disease, but also can be exploited as a therapeutic tool. However, the ‘humanization’ of murine monoclonal antibodies (mAbs) is a time-consuming and expensive process that has the inherent drawback of potentially altering antigenic specificity and/or affinity. The immortalization of human B cells represents an alternative for obtaining human mAbs, but relies on the availability of biological samples from vaccinated individuals or convalescent patients. In this work we describe a novel approach to generate fully human mAbs by combining a humanized mouse model with a new B cell immortalization technique. METHODOLOGY/PRINCIPAL FINDINGS: After transplantation with CD34(+)CD38(−) human hematopoietic progenitor cells, BALB/c Rag2(−/−)IL-2Rγc(−/−) mice acquire a human immune system and harbor B cells with a diverse IgM repertoire. “Human Immune System” mice were then immunized with two commercial vaccine antigens, tetanus toxoid and hepatitis B surface antigen. Sorted human CD19(+)CD27(+) B cells were retrovirally transduced with the human B cell lymphoma (BCL)-6 and BCL-XL genes, and subsequently cultured in the presence of CD40-ligand and IL-21. This procedure allows generating stable B cell receptor-positive B cells that secrete immunoglobulins. We recovered stable B cell clones that produced IgM specific for tetanus toxoid and the hepatitis B surface antigen, respectively. CONCLUSION/SIGNIFICANCE: This work provides the proof-of-concept for the usefulness of this novel method based on the immunization of humanized mice for the rapid generation of human mAbs against a wide range of antigens.",2010 Oct 4,"['Becker, Pablo D.', 'Legrand, Nicolas', 'van Geelen, Caroline M. M.', 'Noerder, Miriam', 'Huntington, Nicholas D.', 'Lim, Annick', 'Yasuda, Etsuko', 'Diehl, Sean A.', 'Scheeren, Ferenc A.', 'Ott, Michael', 'Weijer, Kees', 'Wedemeyer, Heiner', 'Di Santo, James P.', 'Beaumont, Tim', 'Guzman, Carlos A.', 'Spits, Hergen']",PLoS One,,,False
cf665ea806b5a1b271c377e3826bf9d8bd0ebf9f,PMC,Profiling of cellular proteins in porcine reproductive and respiratory syndrome virus virions by proteomics analysis,http://dx.doi.org/10.1186/1743-422X-7-242,PMC2949843,20849641,CC BY,"BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped virus, bearing severe economic consequences to the swine industry worldwide. Previous studies on enveloped viruses have shown that many incorporated cellular proteins associated with the virion's membranes that might play important roles in viral infectivity. In this study, we sought to proteomically profile the cellular proteins incorporated into or associated with the virions of a highly virulent PRRSV strain GDBY1, and to provide foundation for further investigations on the roles of incorporated/associated cellular proteins on PRRSV's infectivity. RESULTS: In our experiment, sixty one cellular proteins were identified in highly purified PRRSV virions by two-dimensional gel electrophoresis coupled with mass spectrometric approaches. The identified cellular proteins could be grouped into eight functional categories including cytoskeletal proteins, chaperones, macromolecular biosynthesis proteins, metabolism-associated proteins, calcium-dependent membrane-binding proteins and other functional proteins. Among the identified proteins, four have not yet been reported in other studied envelope viruses, namely, guanine nucleotide-binding proteins, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase, peroxiredoxin 1 and galectin-1 protein. The presence of five selected cellular proteins (i.e., β-actin, Tubulin, Annexin A2, heat shock protein Hsp27, and calcium binding proteins S100) in the highly purified PRRSV virions was validated by Western blot and immunogold labeling assays. CONCLUSIONS: Taken together, the present study has demonstrated the incorporation of cellular proteins in PRRSV virions, which provides valuable information for the further investigations for the effects of individual cellular proteins on the viral replication, assembly, and pathogenesis.",2010 Sep 18,"['Zhang, Chengwen', 'Xue, Chunyi', 'Li, Yan', 'Kong, Qingming', 'Ren, Xiangpeng', 'Li, Xiaoming', 'Shu, Dingming', 'Bi, Yingzuo', 'Cao, Yongchang']",Virol J,,,True
d15737a61bc7a5c77a10ff81579ab5ffcaab4393,PMC,Selective gene silencing by viral delivery of short hairpin RNA,http://dx.doi.org/10.1186/1743-422X-7-248,PMC2949849,20858246,CC BY,"RNA interference (RNAi) technology has not only become a powerful tool for functional genomics, but also allows rapid drug target discovery and in vitro validation of these targets in cell culture. Furthermore, RNAi represents a promising novel therapeutic option for treating human diseases, in particular cancer. Selective gene silencing by RNAi can be achieved essentially by two nucleic acid based methods: i) cytoplasmic delivery of short double-stranded (ds) interfering RNA oligonucleotides (siRNA), where the gene silencing effect is only transient in nature, and possibly not suitable for all applications; or ii) nuclear delivery of gene expression cassettes that express short hairpin RNA (shRNA), which are processed like endogenous interfering RNA and lead to stable gene down-regulation. Both processes involve the use of nucleic acid based drugs, which are highly charged and do not cross cell membranes by free diffusion. Therefore, in vivo delivery of RNAi therapeutics must use technology that enables the RNAi therapeutic to traverse biological membrane barriers in vivo. Viruses and the vectors derived from them carry out precisely this task and have become a major delivery system for shRNA. Here, we summarize and compare different currently used viral delivery systems, give examples of in vivo applications, and indicate trends for new developments, such as replicating viruses for shRNA delivery to cancer cells.",2010 Sep 21,"['Sliva, Katja', 'Schnierle, Barbara S']",Virol J,,,True
37485356ce87c19f6d32121ed6b64b28c3041c24,PMC,Reflections on Pandemic (H1N1) 2009 and the International Response,http://dx.doi.org/10.1371/journal.pmed.1000346,PMC2950129,20957189,CC BY,"Gabriel Leung and Angus Nicoll provide their reflections on the international response to the 2009 H1N1 influenza pandemic, including what went well and what changes need to be made in anticipation of future flu pandemics.",2010 Oct 5,"['Leung, Gabriel M.', 'Nicoll, Angus']",PLoS Med,,,True
e86b3861c3d400a8a5baf860545af22254fc9c0b,PMC,Profiling of Substrate Specificity of SARS-CoV 3CL(pro),http://dx.doi.org/10.1371/journal.pone.0013197,PMC2950840,20949131,CC BY,"BACKGROUND: The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome-coronavirus is required for autoprocessing of the polyprotein, and is a potential target for treating coronaviral infection. METHODOLOGY/PRINCIPAL FINDINGS: To obtain a thorough understanding of substrate specificity of the protease, a substrate library of 19[Image: see text]8 variants was created by performing saturation mutagenesis on the autocleavage sequence at P5 to P3' positions. The substrate sequences were inserted between cyan and yellow fluorescent proteins so that the cleavage rates were monitored by in vitro fluorescence resonance energy transfer. The relative cleavage rate for different substrate sequences was correlated with various structural properties. P5 and P3 positions prefer residues with high β-sheet propensity; P4 prefers small hydrophobic residues; P2 prefers hydrophobic residues without β-branch. Gln is the best residue at P1 position, but observable cleavage can be detected with His and Met substitutions. P1' position prefers small residues, while P2' and P3' positions have no strong preference on residue substitutions. Noteworthy, solvent exposed sites such as P5, P3 and P3' positions favour positively charged residues over negatively charged one, suggesting that electrostatic interactions may play a role in catalysis. A super-active substrate, which combined the preferred residues at P5 to P1 positions, was found to have 2.8 fold higher activity than the wild-type sequence. CONCLUSIONS/SIGNIFICANCE: Our results demonstrated a strong structure-activity relationship between the 3CL(pro) and its substrate. The substrate specificity profiled in this study may provide insights into a rational design of peptidomimetic inhibitors.",2010 Oct 6,"['Chuck, Chi-Pang', 'Chong, Lin-Tat', 'Chen, Chao', 'Chow, Hak-Fun', 'Wan, David Chi-Cheong', 'Wong, Kam-Bo']",PLoS One,,,True
28e355b80d2d62c5314e8d97e92fbd67f77679d5,PMC,A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case,http://dx.doi.org/10.1371/journal.pone.0013315,PMC2953511,20976271,CC BY,"Autopsy studies have shown that human highly pathogenic avian influenza virus (H5N1) can infect multiple human organs other than just the lungs, and that possible causes of organ damage are either viral replication and/or dysregulation of cytokines and chemokines. Uncertainty still exists, partly because of the limited number of cases analysed. In this study, a full autopsy including 5 organ systems was conducted on a confirmed H5N1 human fatal case (male, 42 years old) within 18 hours of death. In addition to the respiratory system (lungs, bronchus and trachea), virus was isolated from cerebral cortex, cerebral medullary substance, cerebellum, brain stem, hippocampus ileum, colon, rectum, ureter, aortopulmonary vessel and lymph-node. Real time RT-PCR evidence showed that matrix and hemagglutinin genes were positive in liver and spleen in addition to positive tissues with virus isolation. Immunohistochemistry and in-situ hybridization stains showed accordant evidence of viral infection with real time RT-PCR except bronchus. Quantitative RT-PCR suggested that a high viral load was associated with increased host responses, though the viral load was significantly different in various organs. Cells of the immunologic system could also be a target for virus infection. Overall, the pathogenesis of HPAI H5N1 virus was associated both with virus replication and with immunopathologic lesions. In addition, immune cells cannot be excluded from playing a role in dissemination of the virus in vivo.",2010 Oct 12,"['Gao, Rongbao', 'Dong, Libo', 'Dong, Jie', 'Wen, Leying', 'Zhang, Ye', 'Yu, Hongjie', 'Feng, Zijian', 'Chen, Minmei', 'Tan, Yi', 'Mo, Zhaojun', 'Liu, Haiyan', 'Fan, Yunyan', 'Li, Kunxiong', 'Li, Chris Ka-Fai', 'Li, Dexin', 'Yang, Weizhong', 'Shu, Yuelong']",PLoS One,,,True
b35c5f90e09d90f6fd6cff9dab355755e4c33fe4,PMC,Situational Awareness and Health Protective Responses to Pandemic Influenza A (H1N1) in Hong Kong: A Cross-Sectional Study,http://dx.doi.org/10.1371/journal.pone.0013350,PMC2953514,20967280,CC BY,"BACKGROUND: Whether information sources influence health protective behaviours during influenza pandemics or other emerging infectious disease epidemics is uncertain. METHODOLOGY: Data from cross-sectional telephone interviews of 1,001 Hong Kong adults in June, 2009 were tested against theory and data-derived hypothesized associations between trust in (formal/informal) information, understanding, self-efficacy, perceived susceptibility and worry, and hand hygiene and social distancing using Structural Equation Modelling with multigroup comparisons. PRINCIPAL FINDINGS: Trust in formal (government/media) information about influenza was associated with greater reported understanding of A/H1N1 cause (β = 0.36) and A/H1N1 prevention self-efficacy (β = 0.25), which in turn were associated with more hand hygiene (β = 0.19 and β = 0.23, respectively). Trust in informal (interpersonal) information was negatively associated with perceived personal A/H1N1 susceptibility (β = −0.21), which was negatively associated with perceived self-efficacy (β = −0.42) but positively associated with influenza worry (β = 0.44). Trust in informal information was positively associated with influenza worry (β = 0.16) which was in turn associated with greater social distancing (β = 0.36). Multigroup comparisons showed gender differences regarding paths from trust in formal information to understanding of A/H1N1 cause, trust in informal information to understanding of A/H1N1 cause, and understanding of A/H1N1 cause to perceived self-efficacy. CONCLUSIONS/SIGNIFICANCE: Trust in government/media information was more strongly associated with greater self-efficacy and handwashing, whereas trust in informal information was strongly associated with perceived health threat and avoidance behaviour. Risk communication should consider the effect of gender differences.",2010 Oct 12,"['Liao, Qiuyan', 'Cowling, Benjamin', 'Lam, Wing Tak', 'Ng, Man Wai', 'Fielding, Richard']",PLoS One,,,True
2d298d793c2521ceebdcd2c4be960591032ae0d3,PMC,Human Anti-Plague Monoclonal Antibodies Protect Mice from Yersinia pestis in a Bubonic Plague Model,http://dx.doi.org/10.1371/journal.pone.0013047,PMC2954148,20976274,CC0,"Yersinia pestis is the etiologic agent of plague that has killed more than 200 million people throughout the recorded history of mankind. Antibiotics may provide little immediate relief to patients who have a high bacteremia or to patients infected with an antibiotic resistant strain of plague. Two virulent factors of Y. pestis are the capsid F1 protein and the low-calcium response (Lcr) V-protein or V-antigen that have been proven to be the targets for both active and passive immunization. There are mouse monoclonal antibodies (mAbs) against the F1- and V-antigens that can passively protect mice in a murine model of plague; however, there are no anti-Yersinia pestis monoclonal antibodies available for prophylactic or therapeutic treatment in humans. We identified one anti-F1-specific human mAb (m252) and two anti-V-specific human mAb (m253, m254) by panning a naïve phage-displayed Fab library against the F1- and V-antigens. The Fabs were converted to IgG1s and their binding and protective activities were evaluated. M252 bound weakly to peptides located at the F1 N-terminus where a protective mouse anti-F1 mAb also binds. M253 bound strongly to a V-antigen peptide indicating a linear epitope; m254 did not bind to any peptide from a panel of 53 peptides suggesting that its epitope may be conformational. M252 showed better protection than m253 and m254 against a Y, pestis challenge in a plague mouse model. A synergistic effect was observed when the three antibodies were combined. Incomplete to complete protection was achieved when m252 was given at different times post-challenge. These antibodies can be further studied to determine their potential as therapeutics or prophylactics in Y. pestis infection in humans.",2010 Oct 13,"['Xiao, Xiaodong', 'Zhu, Zhongyu', 'Dankmeyer, Jennifer L.', 'Wormald, Michael M.', 'Fast, Randy L.', 'Worsham, Patricia L.', 'Cote, Christopher K.', 'Amemiya, Kei', 'Dimitrov, Dimiter S.']",PLoS One,,,True
311d15fee68d2a591ffc4e7cc0187b8dae872f9c,PMC,Combining Free Text and Structured Electronic Medical Record Entries to Detect Acute Respiratory Infections,http://dx.doi.org/10.1371/journal.pone.0013377,PMC2954790,20976281,CC BY,"BACKGROUND: The electronic medical record (EMR) contains a rich source of information that could be harnessed for epidemic surveillance. We asked if structured EMR data could be coupled with computerized processing of free-text clinical entries to enhance detection of acute respiratory infections (ARI). METHODOLOGY: A manual review of EMR records related to 15,377 outpatient visits uncovered 280 reference cases of ARI. We used logistic regression with backward elimination to determine which among candidate structured EMR parameters (diagnostic codes, vital signs and orders for tests, imaging and medications) contributed to the detection of those reference cases. We also developed a computerized free-text search to identify clinical notes documenting at least two non-negated ARI symptoms. We then used heuristics to build case-detection algorithms that best combined the retained structured EMR parameters with the results of the text analysis. PRINCIPAL FINDINGS: An adjusted grouping of diagnostic codes identified reference ARI patients with a sensitivity of 79%, a specificity of 96% and a positive predictive value (PPV) of 32%. Of the 21 additional structured clinical parameters considered, two contributed significantly to ARI detection: new prescriptions for cough remedies and elevations in body temperature to at least 38°C. Together with the diagnostic codes, these parameters increased detection sensitivity to 87%, but specificity and PPV declined to 95% and 25%, respectively. Adding text analysis increased sensitivity to 99%, but PPV dropped further to 14%. Algorithms that required satisfying both a query of structured EMR parameters as well as text analysis disclosed PPVs of 52–68% and retained sensitivities of 69–73%. CONCLUSION: Structured EMR parameters and free-text analyses can be combined into algorithms that can detect ARI cases with new levels of sensitivity or precision. These results highlight potential paths by which repurposed EMR information could facilitate the discovery of epidemics before they cause mass casualties.",2010 Oct 14,"['DeLisle, Sylvain', 'South, Brett', 'Anthony, Jill A.', 'Kalp, Ericka', 'Gundlapallli, Adi', 'Curriero, Frank C.', 'Glass, Greg E.', 'Samore, Matthew', 'Perl, Trish M.']",PLoS One,,,True
c05053ab5281d6f0329a0b2b124acf02fb5875b7,PMC,High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing,http://dx.doi.org/10.1371/journal.ppat.1001146,PMC2954836,20976195,CC0,"We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system.",2010 Oct 14,"['Beitzel, Brett F.', 'Bakken, Russell R.', 'Smith, Jeffrey M.', 'Schmaljohn, Connie S.']",PLoS Pathog,,,True
4e9b9412e96583aaca4e9f9a305fd7444859c34b,PMC,High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing,http://dx.doi.org/10.1371/journal.ppat.1001146,PMC2954836,20976195,CC0,"We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system.",2010 Oct 14,"['Beitzel, Brett F.', 'Bakken, Russell R.', 'Smith, Jeffrey M.', 'Schmaljohn, Connie S.']",PLoS Pathog,,,False
45b9123437117a4568919c5ef48cdad3bf5410cd,PMC,High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing,http://dx.doi.org/10.1371/journal.ppat.1001146,PMC2954836,20976195,CC0,"We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system.",2010 Oct 14,"['Beitzel, Brett F.', 'Bakken, Russell R.', 'Smith, Jeffrey M.', 'Schmaljohn, Connie S.']",PLoS Pathog,,,False
7ad712a652dcfa7e01cf192177602296e1c5bf1a,PMC,High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing,http://dx.doi.org/10.1371/journal.ppat.1001146,PMC2954836,20976195,CC0,"We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system.",2010 Oct 14,"['Beitzel, Brett F.', 'Bakken, Russell R.', 'Smith, Jeffrey M.', 'Schmaljohn, Connie S.']",PLoS Pathog,,,False
34a95c9d94919eaef9a5bb6a863cf75a41d8e10a,PMC,High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing,http://dx.doi.org/10.1371/journal.ppat.1001146,PMC2954836,20976195,CC0,"We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system.",2010 Oct 14,"['Beitzel, Brett F.', 'Bakken, Russell R.', 'Smith, Jeffrey M.', 'Schmaljohn, Connie S.']",PLoS Pathog,,,False
e59cf9611fc13cb4b124e5677ba3290a3c6bf7d7,PMC,High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing,http://dx.doi.org/10.1371/journal.ppat.1001146,PMC2954836,20976195,CC0,"We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system.",2010 Oct 14,"['Beitzel, Brett F.', 'Bakken, Russell R.', 'Smith, Jeffrey M.', 'Schmaljohn, Connie S.']",PLoS Pathog,,,False
7d07ea5145ff28047a49998617c8e015c5d19ece,PMC,High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing,http://dx.doi.org/10.1371/journal.ppat.1001146,PMC2954836,20976195,CC0,"We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system.",2010 Oct 14,"['Beitzel, Brett F.', 'Bakken, Russell R.', 'Smith, Jeffrey M.', 'Schmaljohn, Connie S.']",PLoS Pathog,,,False
13194f8e42df83d260e53ad9bf7448577e9319e5,PMC,Identification and characterization of a virus-specific continuous B-cell epitope on the PrM/M protein of Japanese Encephalitis Virus: potential application in the detection of antibodies to distinguish Japanese Encephalitis Virus infection from West Nile Virus and Dengue Virus infections,http://dx.doi.org/10.1186/1743-422X-7-249,PMC2954857,20858291,CC BY,"BACKGROUND: Differential diagnose of Japanese encephalitis virus (JEV) infection from other flavivirus especially West Nile virus (WNV) and Dengue virus (DV) infection was greatly hindered for the serological cross-reactive. Virus specific epitopes could benefit for developing JEV specific antibodies detection methods. To identify the JEV specific epitopes, we fully mapped and characterized the continuous B-cell epitope of the PrM/M protein of JEV. RESULTS: To map the epitopes on the PrM/M protein, we designed a set of 20 partially overlapping fragments spanning the whole PrM, fused them with GST, and expressed them in an expression vector. Linear epitope M14 ((105)VNKKEAWLDSTKATRY(120)) was detected by enzyme-linked immunosorbent assay (ELISA). By removing amino acid residues individually from the carboxy and amino terminal of peptide M14, we confirmed that the minimal unit of the linear epitope of PrM/M was M14-13 ((108)KEAWLDSTKAT(118)). This epitope was highly conserved across different JEV strains. Moreover, this epitope did not cross-react with WNV-positive and DENV-positive sera. CONCLUSION: Epitope M14-13 was a JEV specific lineal B-cell epitpe. The results may provide a useful basis for the development of epitope-based virus specific diagnostic clinical techniques.",2010 Sep 22,"['Hua, Rong-Hong', 'Chen, Na-Sha', 'Qin, Cheng-Feng', 'Deng, Yong-Qiang', 'Ge, Jin-Ying', 'Wang, Xi-Jun', 'Qiao, Zu-Jian', 'Chen, Wei-Ye', 'Wen, Zhi-Yuan', 'Liu, Wen-Xin', 'Hu, Sen', 'Bu, Zhi-Gao']",Virol J,,,True
4cc161090a796945e7bda63489feb4f268bfeb3a,PMC,Identification of NCAM that interacts with the PHE-CoV spike protein,http://dx.doi.org/10.1186/1743-422X-7-254,PMC2955716,20863409,CC BY,"BACKGROUND: The spike proteins of coronaviruses associate with cellular molecules to mediate infection of their target cells. The characterization of cellular proteins required for virus infection is essential for understanding viral life cycles and may provide cellular targets for antiviral therapies. RESULTS: We identified Neural Cell Adhesion Molecule (NCAM) as a novel interacting partner of the PHE-CoV S protein. A T7 phage display cDNA library from N2a cells was constructed, and the library was screened with the soluble PHE-CoV S glycoproteins. We used a coimmunoprecipitation assay to show that only the NCAM was a binding partner of spike protein. We found that a soluble form of anti-NCAM antibody blocked association of the PHE-CoV with N2a cells. Furthermore, double-stranded siRNA targeted against NCAM inhibited PHE-CoV infection. CONCLUSIONS: A novel interaction was identified between NCAM and spike protein and this association is critical during PHE-CoV infection.",2010 Sep 24,"['Gao, Wei', 'He, Wenqi', 'Zhao, Kui', 'Lu, Huijun', 'Ren, Wenzhi', 'Du, Chongtao', 'Chen, Keyan', 'Lan, Yungang', 'Song, Deguang', 'Gao, Feng']",Virol J,,,True
ccfba2653a0baee4d4a733902529dc5c96bc69d5,PMC,A Metagenomic Analysis of Pandemic Influenza A (2009 H1N1) Infection in Patients from North America,http://dx.doi.org/10.1371/journal.pone.0013381,PMC2956640,20976137,CC BY,"Although metagenomics has been previously employed for pathogen discovery, its cost and complexity have prevented its use as a practical front-line diagnostic for unknown infectious diseases. Here we demonstrate the utility of two metagenomics-based strategies, a pan-viral microarray (Virochip) and deep sequencing, for the identification and characterization of 2009 pandemic H1N1 influenza A virus. Using nasopharyngeal swabs collected during the earliest stages of the pandemic in Mexico, Canada, and the United States (n = 17), the Virochip was able to detect a novel virus most closely related to swine influenza viruses without a priori information. Deep sequencing yielded reads corresponding to 2009 H1N1 influenza in each sample (percentage of aligned sequences corresponding to 2009 H1N1 ranging from 0.0011% to 10.9%), with up to 97% coverage of the influenza genome in one sample. Detection of 2009 H1N1 by deep sequencing was possible even at titers near the limits of detection for specific RT-PCR, and the percentage of sequence reads was linearly correlated with virus titer. Deep sequencing also provided insights into the upper respiratory microbiota and host gene expression in response to 2009 H1N1 infection. An unbiased analysis combining sequence data from all 17 outbreak samples revealed that 90% of the 2009 H1N1 genome could be assembled de novo without the use of any reference sequence, including assembly of several near full-length genomic segments. These results indicate that a streamlined metagenomics detection strategy can potentially replace the multiple conventional diagnostic tests required to investigate an outbreak of a novel pathogen, and provide a blueprint for comprehensive diagnosis of unexplained acute illnesses or outbreaks in clinical and public health settings.",2010 Oct 18,"['Greninger, Alexander L.', 'Chen, Eunice C.', 'Sittler, Taylor', 'Scheinerman, Alex', 'Roubinian, Nareg', 'Yu, Guixia', 'Kim, Edward', 'Pillai, Dylan R.', 'Guyard, Cyril', 'Mazzulli, Tony', 'Isa, Pavel', 'Arias, Carlos F.', 'Hackett, John', 'Schochetman, Gerald', 'Miller, Steve', 'Tang, Patrick', 'Chiu, Charles Y.']",PLoS One,,,True
d4d0092e3e79f9d5ad3c48f23778317ad867d61c,PMC,Nodeomics: Pathogen Detection in Vertebrate Lymph Nodes Using Meta-Transcriptomics,http://dx.doi.org/10.1371/journal.pone.0013432,PMC2956653,20976145,CC0,"The ongoing emergence of human infections originating from wildlife highlights the need for better knowledge of the microbial community in wildlife species where traditional diagnostic approaches are limited. Here we evaluate the microbial biota in healthy mule deer (Odocoileus hemionus) by analyses of lymph node meta-transcriptomes. cDNA libraries from five individuals and two pools of samples were prepared from retropharyngeal lymph node RNA enriched for polyadenylated RNA and sequenced using Roche-454 Life Sciences technology. Protein-coding and 16S ribosomal RNA (rRNA) sequences were taxonomically profiled using protein and rRNA specific databases. Representatives of all bacterial phyla were detected in the seven libraries based on protein-coding transcripts indicating that viable microbiota were present in lymph nodes. Residents of skin and rumen, and those ubiquitous in mule deer habitat dominated classifiable bacterial species. Based on detection of both rRNA and protein-coding transcripts, we identified two new proteobacterial species; a Helicobacter closely related to Helicobacter cetorum in the Helicobacter pylori/Helicobacter acinonychis complex and an Acinetobacter related to Acinetobacter schindleri. Among viruses, a novel gamma retrovirus and other members of the Poxviridae and Retroviridae were identified. We additionally evaluated bacterial diversity by amplicon sequencing the hypervariable V6 region of 16S rRNA and demonstrate that overall taxonomic diversity is higher with the meta-transcriptomic approach. These data provide the most complete picture to date of the microbial diversity within a wildlife host. Our research advances the use of meta-transcriptomics to study microbiota in wildlife tissues, which will facilitate detection of novel organisms with pathogenic potential to human and animals.",2010 Oct 18,"['Wittekindt, Nicola E.', 'Padhi, Abinash', 'Schuster, Stephan C.', 'Qi, Ji', 'Zhao, Fangqing', 'Tomsho, Lynn P.', 'Kasson, Lindsay R.', 'Packard, Michael', 'Cross, Paul', 'Poss, Mary']",PLoS One,,,True
a2a873c09a0bc1b59d326245310e25a83031cd62,PMC,Advances in Diagnosis of Respiratory Virus Infections,http://dx.doi.org/10.1155/2010/126049,PMC2958490,20981303,CC BY,"The diagnosis of respiratory virus infections has evolved substantially in recent years, with the emergence of new pathogens and the development of novel detection methods. While recent advances have improved the sensitivity and turn-around time of diagnostic tests for respiratory viruses, they have also raised important issues such as cost, and the clinical significance of detecting multiple viruses in a single specimen by molecular methods. This article reviews recent advances in specimen collection and detection methods for diagnosis of respiratory virus infections, and discusses the performance characteristics and limitations of these methods.",2010 Oct 19,"['Loeffelholz, Michael', 'Chonmaitree, Tasnee']",Int J Microbiol,,,True
39772fc7033bdfcfd0a6fb689d7a5c8bff2d80e1,PMC,In Vitro and In Vivo Studies Identify Important Features of Dengue Virus pr-E Protein Interactions,http://dx.doi.org/10.1371/journal.ppat.1001157,PMC2958806,20975939,CC BY,"Flaviviruses bud into the endoplasmic reticulum and are transported through the secretory pathway, where the mildly acidic environment triggers particle rearrangement and allows furin processing of the prM protein to pr and M. The peripheral pr peptide remains bound to virus at low pH and inhibits virus-membrane interaction. Upon exocytosis, the release of pr at neutral pH completes virus maturation to an infectious particle. Together this evidence suggests that pr may shield the flavivirus fusion protein E from the low pH environment of the exocytic pathway. Here we developed an in vitro system to reconstitute the interaction of dengue virus (DENV) pr with soluble truncated E proteins. At low pH recombinant pr bound to both monomeric and dimeric forms of E and blocked their membrane insertion. Exogenous pr interacted with mature infectious DENV and specifically inhibited virus fusion and infection. Alanine substitution of E H244, a highly conserved histidine residue in the pr-E interface, blocked pr-E interaction and reduced release of DENV virus-like particles. Folding, membrane insertion and trimerization of the H244A mutant E protein were preserved, and particle release could be partially rescued by neutralization of the low pH of the secretory pathway. Thus, pr acts to silence flavivirus fusion activity during virus secretion, and this function can be separated from the chaperone activity of prM. The sequence conservation of key residues involved in the flavivirus pr-E interaction suggests that this protein-protein interface may be a useful target for broad-spectrum inhibitors.",2010 Oct 21,"['Zheng, Aihua', 'Umashankar, Mahadevaiah', 'Kielian, Margaret']",PLoS Pathog,,,True
96996147e2d12f5db12dd32d730fd694be627d6f,PMC,In Vitro and In Vivo Studies Identify Important Features of Dengue Virus pr-E Protein Interactions,http://dx.doi.org/10.1371/journal.ppat.1001157,PMC2958806,20975939,CC BY,"Flaviviruses bud into the endoplasmic reticulum and are transported through the secretory pathway, where the mildly acidic environment triggers particle rearrangement and allows furin processing of the prM protein to pr and M. The peripheral pr peptide remains bound to virus at low pH and inhibits virus-membrane interaction. Upon exocytosis, the release of pr at neutral pH completes virus maturation to an infectious particle. Together this evidence suggests that pr may shield the flavivirus fusion protein E from the low pH environment of the exocytic pathway. Here we developed an in vitro system to reconstitute the interaction of dengue virus (DENV) pr with soluble truncated E proteins. At low pH recombinant pr bound to both monomeric and dimeric forms of E and blocked their membrane insertion. Exogenous pr interacted with mature infectious DENV and specifically inhibited virus fusion and infection. Alanine substitution of E H244, a highly conserved histidine residue in the pr-E interface, blocked pr-E interaction and reduced release of DENV virus-like particles. Folding, membrane insertion and trimerization of the H244A mutant E protein were preserved, and particle release could be partially rescued by neutralization of the low pH of the secretory pathway. Thus, pr acts to silence flavivirus fusion activity during virus secretion, and this function can be separated from the chaperone activity of prM. The sequence conservation of key residues involved in the flavivirus pr-E interaction suggests that this protein-protein interface may be a useful target for broad-spectrum inhibitors.",2010 Oct 21,"['Zheng, Aihua', 'Umashankar, Mahadevaiah', 'Kielian, Margaret']",PLoS Pathog,,,False
0049ba8861864506e1e8559e7815f4de8b03dbed,PMC,GPI-anchored single chain Fv - an effective way to capture transiently-exposed neutralization epitopes on HIV-1 envelope spike,http://dx.doi.org/10.1186/1742-4690-7-79,PMC2959034,20923574,CC BY,"BACKGROUND: Identification of broad neutralization epitopes in HIV-1 envelope spikes is paramount for HIV-1 vaccine development. A few broad neutralization epitopes identified so far are present on the surface of native HIV-1 envelope spikes whose recognition by antibodies does not depend on conformational changes of the envelope spikes. However, HIV-1 envelope spikes also contain transiently-exposed neutralization epitopes, which are more difficult to identify. RESULTS: In this study, we constructed single chain Fvs (scFvs) derived from seven human monoclonal antibodies and genetically linked them with or without a glycosyl-phosphatidylinositol (GPI) attachment signal. We show that with a GPI attachment signal the scFvs are targeted to lipid rafts of plasma membranes. In addition, we demonstrate that four of the GPI-anchored scFvs, but not their secreted counterparts, neutralize HIV-1 with various degrees of breadth and potency. Among them, GPI-anchored scFv (X5) exhibits extremely potent and broad neutralization activity against multiple clades of HIV-1 strains tested. Moreover, we show that GPI-anchored scFv (4E10) also exhibited more potent neutralization activity than its secretory counterpart. Finally, we demonstrate that expression of GPI-anchored scFv (X5) in the lipid raft of plasma membrane of human CD4(+ )T cells confers long-term resistance to HIV-1 infection, HIV-1 envelope-mediated cell-cell fusion, and the infection of HIV-1 captured and transferred by human DCs. CONCLUSIONS: Thus GPI-anchored scFv could be used as a general and effective way to identify antibodies that react with transiently-exposed neutralization epitopes in envelope proteins of HIV-1 and other enveloped viruses. The GPI-anchored scFv (X5), because of its breadth and potency, should have a great potential to be developed into anti-viral agent for HIV-1 prevention and therapy.",2010 Oct 6,"['Wen, Michael', 'Arora, Reetakshi', 'Wang, Huiqiang', 'Liu, Lihong', 'Kimata, Jason T', 'Zhou, Paul']",Retrovirology,,,True
611159c87e69ac113f1652442897b3cf96878939,PMC,C-reactive protein serum levels as an early predictor of outcome in patients with pandemic H1N1 influenza A virus infection,http://dx.doi.org/10.1186/1471-2334-10-288,PMC2959060,20920320,CC BY,"BACKGROUND: Data for predicting which patients with pandemic influenza A (H1N1) infection are likely to run a complicated course are sparse. We retrospectively studied whether the admission serum C-reactive protein (CRP) levels can serve as a predictor of illness severity. METHODS: Included were all consecutive adult patients who presented to the emergency department (ED) between May-December, 2009 with a flu-like illness, a confirmed diagnosis of pandemic influenza A (H1N1) infection and a serum CRP level measured within 24 hours of presentation. Patients with a proven additional concurrent acute illness (e.g., bacteremia) were excluded. We used the ROC curve analysis, Kaplan-Meier curves and the Cox proportional hazard model to evaluate the predictive ability of CRP as a prognostic factor. RESULTS: Seventeen (9%) of the 191 enrolled patients were admitted to the intensive care unit (ICU), of whom eight (4%) required mechanical ventilation and three (2%) died. The median admission serum CRP levels were significantly higher among patients who required subsequent ICU care and mechanical ventilation than among patients who did not (123 mg/L and 112 mg/L vs. 40 mg/L, p < .001 and 43 mg/L, p = .017, respectively). A Cox proportional hazard model identified admission serum CRP levels and auscultatory findings over the lungs as independent prognostic factors for ICU admission. Admission serum CRP levels were the only independent prognostic factor for mechanical ventilation. Thirty days after presenting to the ED, none of the patients with admission serum CRP level <28 mg/L (lower tertile) required either ICU admission or mechanical ventilation. At the same time point, 19% of the patients with admission serum CRP level ≥70 mg/L (upper tertile) needed to be admitted to the ICU and 8% of the same upper tertile group required mechanical ventilation. The differences in the rates between the lower vs. upper tertile groups were significant (Log-Rank p < .001 for ICU and p < .024 for mechanical ventilation). CONCLUSIONS: In our study group, serum CRP levels obtained in the early ED admission stage from patients presenting with pandemic H1N1 influenza A infection were found to serve as a useful gauge for predicting disease course and assisting in patient management.",2010 Oct 4,"['Zimmerman, Ofer', 'Rogowski, Ori', 'Aviram, Galit', 'Mizrahi, Michal', 'Zeltser, David', 'Justo, Dan', 'Dahan, Esther', 'Arad, Roy', 'Touvia, Oholi', 'Tau, Luba', 'Tarabeia, Jalal', 'Berliner, Shlomo', 'Paran, Yael']",BMC Infect Dis,,,True
8a584984728d9dd104a0d3928686d4a2e02e2ebf,PMC,The dynamics of risk perceptions and precautionary behavior in response to 2009 (H1N1) pandemic influenza,http://dx.doi.org/10.1186/1471-2334-10-296,PMC2964717,20946662,CC BY,"BACKGROUND: The trajectory of an infectious disease outbreak is affected by the behavior of individuals, and the behavior is often related to individuals' risk perception. We assessed temporal changes and geographical differences in risk perceptions and precautionary behaviors in response to H1N1 influenza. METHODS: 1,290 US adults completed an online survey on risk perceptions, interests in pharmaceutical interventions (preventive intervention and curative intervention), and engagement in precautionary activities (information seeking activities and taking quarantine measures) in response to H1N1 influenza between April 28 and May 27 2009. Associations of risk perceptions and precautionary behaviors with respondents' sex, age, and household size were analyzed. Linear and quadratic time trends were assessed by regression analyses. Geographic differences in risk perception and precautionary behaviors were evaluated. Predictors of willingness to take pharmaceutical intervention were analyzed. RESULTS: Respondents from larger households reported stronger interest in taking medications and engaged in more precautionary activities, as would be normatively predicted. Perceived risk increased over time, whereas interest in pharmaceutical preventive interventions and the engagement in some precautionary activities decreased over time. Respondents who live in states with higher H1N1 incidence per population perceived a higher likelihood of influenza infection, but did not express greater interests in pharmaceutical interventions, nor did they engage in a higher degree of precautionary activities. Perceived likelihood of influenza infection, willingness to take medications and engagement in information seeking activities were higher for women than men. CONCLUSIONS: Perceived risk of infection and precautionary behavior can be dynamic in time, and differ by demographic characteristics and geographical locations. These patterns will likely influence the effectiveness of disease control measures.",2010 Oct 14,"['Ibuka, Yoko', 'Chapman, Gretchen B', 'Meyers, Lauren A', 'Li, Meng', 'Galvani, Alison P']",BMC Infect Dis,,,True
68a2d0b2dfdcee12dec8aaf910ccbffc49b83a85,PMC,The dynamics of risk perceptions and precautionary behavior in response to 2009 (H1N1) pandemic influenza,http://dx.doi.org/10.1186/1471-2334-10-296,PMC2964717,20946662,CC BY,"BACKGROUND: The trajectory of an infectious disease outbreak is affected by the behavior of individuals, and the behavior is often related to individuals' risk perception. We assessed temporal changes and geographical differences in risk perceptions and precautionary behaviors in response to H1N1 influenza. METHODS: 1,290 US adults completed an online survey on risk perceptions, interests in pharmaceutical interventions (preventive intervention and curative intervention), and engagement in precautionary activities (information seeking activities and taking quarantine measures) in response to H1N1 influenza between April 28 and May 27 2009. Associations of risk perceptions and precautionary behaviors with respondents' sex, age, and household size were analyzed. Linear and quadratic time trends were assessed by regression analyses. Geographic differences in risk perception and precautionary behaviors were evaluated. Predictors of willingness to take pharmaceutical intervention were analyzed. RESULTS: Respondents from larger households reported stronger interest in taking medications and engaged in more precautionary activities, as would be normatively predicted. Perceived risk increased over time, whereas interest in pharmaceutical preventive interventions and the engagement in some precautionary activities decreased over time. Respondents who live in states with higher H1N1 incidence per population perceived a higher likelihood of influenza infection, but did not express greater interests in pharmaceutical interventions, nor did they engage in a higher degree of precautionary activities. Perceived likelihood of influenza infection, willingness to take medications and engagement in information seeking activities were higher for women than men. CONCLUSIONS: Perceived risk of infection and precautionary behavior can be dynamic in time, and differ by demographic characteristics and geographical locations. These patterns will likely influence the effectiveness of disease control measures.",2010 Oct 14,"['Ibuka, Yoko', 'Chapman, Gretchen B', 'Meyers, Lauren A', 'Li, Meng', 'Galvani, Alison P']",BMC Infect Dis,,,False
d0a71fb07c6dfa2d5d78fdd4be9b7cb8f4be5205,PMC,The dynamics of risk perceptions and precautionary behavior in response to 2009 (H1N1) pandemic influenza,http://dx.doi.org/10.1186/1471-2334-10-296,PMC2964717,20946662,CC BY,"BACKGROUND: The trajectory of an infectious disease outbreak is affected by the behavior of individuals, and the behavior is often related to individuals' risk perception. We assessed temporal changes and geographical differences in risk perceptions and precautionary behaviors in response to H1N1 influenza. METHODS: 1,290 US adults completed an online survey on risk perceptions, interests in pharmaceutical interventions (preventive intervention and curative intervention), and engagement in precautionary activities (information seeking activities and taking quarantine measures) in response to H1N1 influenza between April 28 and May 27 2009. Associations of risk perceptions and precautionary behaviors with respondents' sex, age, and household size were analyzed. Linear and quadratic time trends were assessed by regression analyses. Geographic differences in risk perception and precautionary behaviors were evaluated. Predictors of willingness to take pharmaceutical intervention were analyzed. RESULTS: Respondents from larger households reported stronger interest in taking medications and engaged in more precautionary activities, as would be normatively predicted. Perceived risk increased over time, whereas interest in pharmaceutical preventive interventions and the engagement in some precautionary activities decreased over time. Respondents who live in states with higher H1N1 incidence per population perceived a higher likelihood of influenza infection, but did not express greater interests in pharmaceutical interventions, nor did they engage in a higher degree of precautionary activities. Perceived likelihood of influenza infection, willingness to take medications and engagement in information seeking activities were higher for women than men. CONCLUSIONS: Perceived risk of infection and precautionary behavior can be dynamic in time, and differ by demographic characteristics and geographical locations. These patterns will likely influence the effectiveness of disease control measures.",2010 Oct 14,"['Ibuka, Yoko', 'Chapman, Gretchen B', 'Meyers, Lauren A', 'Li, Meng', 'Galvani, Alison P']",BMC Infect Dis,,,False
68a4cb26f4d7448117bfcb2d2794211c04605765,PMC,The dynamics of risk perceptions and precautionary behavior in response to 2009 (H1N1) pandemic influenza,http://dx.doi.org/10.1186/1471-2334-10-296,PMC2964717,20946662,CC BY,"BACKGROUND: The trajectory of an infectious disease outbreak is affected by the behavior of individuals, and the behavior is often related to individuals' risk perception. We assessed temporal changes and geographical differences in risk perceptions and precautionary behaviors in response to H1N1 influenza. METHODS: 1,290 US adults completed an online survey on risk perceptions, interests in pharmaceutical interventions (preventive intervention and curative intervention), and engagement in precautionary activities (information seeking activities and taking quarantine measures) in response to H1N1 influenza between April 28 and May 27 2009. Associations of risk perceptions and precautionary behaviors with respondents' sex, age, and household size were analyzed. Linear and quadratic time trends were assessed by regression analyses. Geographic differences in risk perception and precautionary behaviors were evaluated. Predictors of willingness to take pharmaceutical intervention were analyzed. RESULTS: Respondents from larger households reported stronger interest in taking medications and engaged in more precautionary activities, as would be normatively predicted. Perceived risk increased over time, whereas interest in pharmaceutical preventive interventions and the engagement in some precautionary activities decreased over time. Respondents who live in states with higher H1N1 incidence per population perceived a higher likelihood of influenza infection, but did not express greater interests in pharmaceutical interventions, nor did they engage in a higher degree of precautionary activities. Perceived likelihood of influenza infection, willingness to take medications and engagement in information seeking activities were higher for women than men. CONCLUSIONS: Perceived risk of infection and precautionary behavior can be dynamic in time, and differ by demographic characteristics and geographical locations. These patterns will likely influence the effectiveness of disease control measures.",2010 Oct 14,"['Ibuka, Yoko', 'Chapman, Gretchen B', 'Meyers, Lauren A', 'Li, Meng', 'Galvani, Alison P']",BMC Infect Dis,,,True
2c6d1fc20495ba6b8b43ffe06cc0d9bb80244d96,PMC,Inhibitory effect of small interfering RNA on dengue virus replication in mosquito cells,http://dx.doi.org/10.1186/1743-422X-7-270,PMC2965154,20946645,CC BY,"BACKGROUND: Dengue viruses (DENs) are the wildest transmitted mosquito-borne pathogens throughout tropical and sub-tropical regions worldwide. Infection with DENs can cause severe flu-like illness and potentially fatal hemorrhagic fever. Although RNA interference triggered by long-length dsRNA was considered a potent antiviral pathway in the mosquito, only limited studies of the value of small interfering RNA (siRNA) have been conducted. RESULTS: A 21 nt siRNA targeting the membrane glycoprotein precursor gene of DEN-1 was synthesized and transfected into mosquito C6/36 cells followed by challenge with DEN. The stability of the siRNA in cells was monitored by flow cytometry. The antiviral effect of siRNA was evaluated by measurement of cell survival rate using the MTT method and viral RNA was quantitated with real-time RT-PCR. The presence of cells containing siRNA at 0.25, 1, 3, 5, 7 days after transfection were 66.0%, 52.1%, 32.0%, 13.5% and 8.9%, respectively. After 7 days incubation with DEN, there was reduced cytopathic effect, increased cell survival rate (76.9 ± 4.5% vs 23.6 ± 14.6%) and reduced viral RNA copies (Ct value 19.91 ± 0.63 vs 14.56 ± 0.39) detected in transfected C6/36 cells. CONCLUSIONS: Our data showed that synthetic siRNA against the DEN-1 membrane glycoprotein precursor gene effectively inhibited DEN-1 viral RNA replication and increased C6/36 cell survival rate. siRNA may offer a potential new strategy for prevention and treatment of DEN infection.",2010 Oct 14,"['Wu, Xinwei', 'Hong, Hua', 'Yue, Jinya', 'Wu, Yejian', 'Li, Xiangzhong', 'Jiang, Liyun', 'Li, Lei', 'Li, Qiaoyan', 'Gao, Guoquan', 'Yang, Xia']",Virol J,,,True
dbaaa5a246123fee5013bba144f693f96e624988,PMC,"Fidelity Variants of RNA Dependent RNA Polymerases Uncover an Indirect, Mutagenic Activity of Amiloride Compounds",http://dx.doi.org/10.1371/journal.ppat.1001163,PMC2965762,21060812,CC BY,"In a screen for RNA mutagen resistance, we isolated a high fidelity RNA dependent RNA polymerase (RdRp) variant of Coxsackie virus B3 (CVB3). Curiously, this variant A372V is also resistant to amiloride. We hypothesize that amiloride has a previously undescribed mutagenic activity. Indeed, amiloride compounds increase the mutation frequencies of CVB3 and poliovirus and high fidelity variants of both viruses are more resistant to this effect. We hypothesize that this mutagenic activity is mediated through alterations in intracellular ions such as Mg(2+) and Mn(2+), which in turn increase virus mutation frequency by affecting RdRp fidelity. Furthermore, we show that another amiloride-resistant RdRp variant, S299T, is completely resistant to this mutagenic activity and unaffected by changes in ion concentrations. We show that RdRp variants resist the mutagenic activity of amiloride via two different mechanisms: 1) increased fidelity that generates virus populations presenting lower basal mutation frequencies or 2) resisting changes in divalent cation concentrations that affect polymerase fidelity. Our results uncover a new antiviral approach based on mutagenesis.",2010 Oct 28,"['Levi, Laura I.', 'Gnädig, Nina F.', 'Beaucourt, Stéphanie', 'McPherson, Malia J.', 'Baron, Bruno', 'Arnold, Jamie J.', 'Vignuzzi, Marco']",PLoS Pathog,,,True
951ba94a08a28e0cc4264dcfd46270625d3efab1,PMC,"Fidelity Variants of RNA Dependent RNA Polymerases Uncover an Indirect, Mutagenic Activity of Amiloride Compounds",http://dx.doi.org/10.1371/journal.ppat.1001163,PMC2965762,21060812,CC BY,"In a screen for RNA mutagen resistance, we isolated a high fidelity RNA dependent RNA polymerase (RdRp) variant of Coxsackie virus B3 (CVB3). Curiously, this variant A372V is also resistant to amiloride. We hypothesize that amiloride has a previously undescribed mutagenic activity. Indeed, amiloride compounds increase the mutation frequencies of CVB3 and poliovirus and high fidelity variants of both viruses are more resistant to this effect. We hypothesize that this mutagenic activity is mediated through alterations in intracellular ions such as Mg(2+) and Mn(2+), which in turn increase virus mutation frequency by affecting RdRp fidelity. Furthermore, we show that another amiloride-resistant RdRp variant, S299T, is completely resistant to this mutagenic activity and unaffected by changes in ion concentrations. We show that RdRp variants resist the mutagenic activity of amiloride via two different mechanisms: 1) increased fidelity that generates virus populations presenting lower basal mutation frequencies or 2) resisting changes in divalent cation concentrations that affect polymerase fidelity. Our results uncover a new antiviral approach based on mutagenesis.",2010 Oct 28,"['Levi, Laura I.', 'Gnädig, Nina F.', 'Beaucourt, Stéphanie', 'McPherson, Malia J.', 'Baron, Bruno', 'Arnold, Jamie J.', 'Vignuzzi, Marco']",PLoS Pathog,,,False
e8392d9561be82ded77c6e5d75f321d752776424,PMC,Prevalence and Phylogeny of Coronaviruses in Wild Birds from the Bering Strait Area (Beringia),http://dx.doi.org/10.1371/journal.pone.0013640,PMC2966397,21060827,CC BY,"Coronaviruses (CoVs) can cause mild to severe disease in humans and animals, their host range and environmental spread seem to have been largely underestimated, and they are currently being investigated for their potential medical relevance. Infectious bronchitis virus (IBV) belongs to gamma-coronaviruses and causes a costly respiratory viral disease in chickens. The role of wild birds in the epidemiology of IBV is poorly understood. In the present study, we examined 1,002 cloacal and faecal samples collected from 26 wild bird species in the Beringia area for the presence of CoVs, and then we performed statistical and phylogenetic analyses. We detected diverse CoVs by RT-PCR in wild birds in the Beringia area. Sequence analysis showed that the detected viruses are gamma-coronaviruses related to IBV. These findings suggest that wild birds are able to carry gamma-coronaviruses asymptomatically. We concluded that CoVs are widespread among wild birds in Beringia, and their geographic spread and frequency is higher than previously realised. Thus, Avian CoV can be efficiently disseminated over large distances and could be a genetic reservoir for future emerging pathogenic CoVs. Considering the great animal health and economic impact of IBV as well as the recent emergence of novel coronaviruses such as SARS-coronavirus, it is important to investigate the role of wildlife reservoirs in CoV infection biology and epidemiology.",2010 Oct 29,"['Muradrasoli, Shaman', 'Bálint, Ádám', 'Wahlgren, John', 'Waldenström, Jonas', 'Belák, Sándor', 'Blomberg, Jonas', 'Olsen, Björn']",PLoS One,,,True
1e7bcacaa32d4c0f5ed60e5e56897404d3896d81,PMC,Real-Time Fluorescence Loop Mediated Isothermal Amplification for the Diagnosis of Malaria,http://dx.doi.org/10.1371/journal.pone.0013733,PMC2966401,21060829,CC0,"BACKGROUND: Molecular diagnostic methods can complement existing tools to improve the diagnosis of malaria. However, they require good laboratory infrastructure thereby restricting their use to reference laboratories and research studies. Therefore, adopting molecular tools for routine use in malaria endemic countries will require simpler molecular platforms. The recently developed loop-mediated isothermal amplification (LAMP) method is relatively simple and can be improved for better use in endemic countries. In this study, we attempted to improve this method for malaria diagnosis by using a simple and portable device capable of performing both the amplification and detection (by fluorescence) of LAMP in one platform. We refer to this as the RealAmp method. METHODOLOGY AND SIGNIFICANT FINDINGS: Published genus-specific primers were used to test the utility of this method. DNA derived from different species of malaria parasites was used for the initial characterization. Clinical samples of P. falciparum were used to determine the sensitivity and specificity of this system compared to microscopy and a nested PCR method. Additionally, directly boiled parasite preparations were compared with a conventional DNA isolation method. The RealAmp method was found to be simple and allowed real-time detection of DNA amplification. The time to amplification varied but was generally less than 60 minutes. All human-infecting Plasmodium species were detected. The sensitivity and specificity of RealAmp in detecting P. falciparum was 96.7% and 91.7% respectively, compared to microscopy and 98.9% and 100% respectively, compared to a standard nested PCR method. In addition, this method consistently detected P. falciparum from directly boiled blood samples. CONCLUSION: This RealAmp method has great potential as a field usable molecular tool for diagnosis of malaria. This tool can provide an alternative to conventional PCR based diagnostic methods for field use in clinical and operational programs.",2010 Oct 29,"['Lucchi, Naomi W.', 'Demas, Allison', 'Narayanan, Jothikumar', 'Sumari, Deborah', 'Kabanywanyi, Abdunoor', 'Kachur, S. Patrick', 'Barnwell, John W.', 'Udhayakumar, Venkatachalam']",PLoS One,,,True
073d9b195e4d3e325a8ec7cd30b9ec23bb0a00a7,PMC,Efficacy of Oseltamivir-Zanamivir Combination Compared to Each Monotherapy for Seasonal Influenza: A Randomized Placebo-Controlled Trial,http://dx.doi.org/10.1371/journal.pmed.1000362,PMC2970549,21072246,CC BY,"BACKGROUND: Neuraminidase inhibitors are thought to be efficacious in reducing the time to alleviation of symptoms in outpatients with seasonal influenza. The objective of this study was to compare the short-term virological efficacy of oseltamivir-zanamivir combination versus each monotherapy plus placebo. METHODS AND FINDINGS: We conducted a randomized placebo-controlled trial with 145 general practitioners throughout France during the 2008–2009 seasonal influenza epidemic. Patients, general practitioners, and outcome assessors were all blinded to treatment assignment. Adult outpatients presenting influenza-like illness for less than 36 hours and a positive influenza A rapid test diagnosis were randomized to oseltamivir 75 mg orally twice daily plus zanamivir 10 mg by inhalation twice daily (OZ), oseltamivir plus inhaled placebo (O), or zanamivir plus oral placebo (Z). Treatment efficacy was assessed virologically according to the proportion of patients with nasal influenza reverse transcription (RT)-PCR below 200 copies genome equivalent (cgeq)/µl at day 2 (primary outcome), and clinically to the time to alleviation of symptoms until day 14. Overall 541 patients (of the 900 planned) were included (OZ, n = 192; O, n = 176; Z, n = 173), 49% male, mean age 39 years. In the intention-to-treat analysis conducted in the 447 patients with RT-PCR-confirmed influenza A, 46%, 59%, and 34% in OZ (n = 157), O (n = 141), and Z (n = 149) arms had RT-PCR<200 cgeq/µl (−13.0%, 95% confidence interval [CI] −23.1 to −2.9, p = 0.025; +12.3%, 95% CI 2.39–22.2, p = 0.028 for OZ/O and OZ/Z comparisons). Mean day 0 to day 2 viral load decrease was 2.14, 2.49, and 1.68 log(10) cgeq/µl (p = 0.060, p = 0.016 for OZ/O and OZ/Z). Median time to alleviation of symptoms was 4.0, 3.0, and 4.0 days (+1.0, 95% CI 0.0–4.0, p = 0.018; +0.0, 95% CI −3.0 to 3.0, p = 0.960 for OZ/O and OZ/Z). Four severe adverse events were observed. Nausea and/or vomiting tended to be more frequent in the combination arm (OZ, n = 13; O, n = 4; and Z, n = 5 patients, respectively). CONCLUSIONS: In adults with seasonal influenza A mainly H3N2 virus infection, the oseltamivir-zanamivir combination appeared less effective than oseltamivir monotherapy, and not significantly more effective than zanamivir monotherapy. Despite the theoretical potential for the reduction of the emergence of antiviral resistance, the lower effectiveness of this combination calls for caution in its use in clinical practice. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00799760 Please see later in the article for the Editors' Summary",2010 Nov 2,"['Duval, Xavier', 'van der Werf, Sylvie', 'Blanchon, Thierry', 'Mosnier, Anne', 'Bouscambert-Duchamp, Maude', 'Tibi, Annick', 'Enouf, Vincent', 'Charlois-Ou, Cécile', 'Vincent, Corine', 'Andreoletti, Laurent', 'Tubach, Florence', 'Lina, Bruno', 'Mentré, France', 'Leport, Catherine', None]",PLoS Med,,,True
21f0073aa9c5c592c81fd9db4e11d61a35865cf7,PMC,Efficacy of Oseltamivir-Zanamivir Combination Compared to Each Monotherapy for Seasonal Influenza: A Randomized Placebo-Controlled Trial,http://dx.doi.org/10.1371/journal.pmed.1000362,PMC2970549,21072246,CC BY,"BACKGROUND: Neuraminidase inhibitors are thought to be efficacious in reducing the time to alleviation of symptoms in outpatients with seasonal influenza. The objective of this study was to compare the short-term virological efficacy of oseltamivir-zanamivir combination versus each monotherapy plus placebo. METHODS AND FINDINGS: We conducted a randomized placebo-controlled trial with 145 general practitioners throughout France during the 2008–2009 seasonal influenza epidemic. Patients, general practitioners, and outcome assessors were all blinded to treatment assignment. Adult outpatients presenting influenza-like illness for less than 36 hours and a positive influenza A rapid test diagnosis were randomized to oseltamivir 75 mg orally twice daily plus zanamivir 10 mg by inhalation twice daily (OZ), oseltamivir plus inhaled placebo (O), or zanamivir plus oral placebo (Z). Treatment efficacy was assessed virologically according to the proportion of patients with nasal influenza reverse transcription (RT)-PCR below 200 copies genome equivalent (cgeq)/µl at day 2 (primary outcome), and clinically to the time to alleviation of symptoms until day 14. Overall 541 patients (of the 900 planned) were included (OZ, n = 192; O, n = 176; Z, n = 173), 49% male, mean age 39 years. In the intention-to-treat analysis conducted in the 447 patients with RT-PCR-confirmed influenza A, 46%, 59%, and 34% in OZ (n = 157), O (n = 141), and Z (n = 149) arms had RT-PCR<200 cgeq/µl (−13.0%, 95% confidence interval [CI] −23.1 to −2.9, p = 0.025; +12.3%, 95% CI 2.39–22.2, p = 0.028 for OZ/O and OZ/Z comparisons). Mean day 0 to day 2 viral load decrease was 2.14, 2.49, and 1.68 log(10) cgeq/µl (p = 0.060, p = 0.016 for OZ/O and OZ/Z). Median time to alleviation of symptoms was 4.0, 3.0, and 4.0 days (+1.0, 95% CI 0.0–4.0, p = 0.018; +0.0, 95% CI −3.0 to 3.0, p = 0.960 for OZ/O and OZ/Z). Four severe adverse events were observed. Nausea and/or vomiting tended to be more frequent in the combination arm (OZ, n = 13; O, n = 4; and Z, n = 5 patients, respectively). CONCLUSIONS: In adults with seasonal influenza A mainly H3N2 virus infection, the oseltamivir-zanamivir combination appeared less effective than oseltamivir monotherapy, and not significantly more effective than zanamivir monotherapy. Despite the theoretical potential for the reduction of the emergence of antiviral resistance, the lower effectiveness of this combination calls for caution in its use in clinical practice. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00799760 Please see later in the article for the Editors' Summary",2010 Nov 2,"['Duval, Xavier', 'van der Werf, Sylvie', 'Blanchon, Thierry', 'Mosnier, Anne', 'Bouscambert-Duchamp, Maude', 'Tibi, Annick', 'Enouf, Vincent', 'Charlois-Ou, Cécile', 'Vincent, Corine', 'Andreoletti, Laurent', 'Tubach, Florence', 'Lina, Bruno', 'Mentré, France', 'Leport, Catherine', None]",PLoS Med,,,True
0add910e9efb81f7b906101a7790b812074dc8b3,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,True
685e9506934c5e4c21c16a02f8c1e11aeeac1bac,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
a7069f86aa3a4d5231c386f08dd28dc3a97b0e0a,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,True
44d0aa144ed562f3811296688dc32d5add62678b,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
2ceafef80beea68922bc46a20a1299a56e5bddeb,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
84c2fe9c415572856b9c3cfc9722fcfc89127b68,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
66a0595238818c1e4e48ba0f89f15ea08f9fd1a6,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
eea89bf2af7757da44d13727fe9d10778352ea6c,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
b2ec5f13ee8c9a0cf5c691dc80e47788560c4e0c,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
131fbbb0a24a397047bb66fce5410c8fb1a5b300,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
362a6ff84fb689abbd3ca367fb077715c3dab5e1,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
930ed6116159ae51ee3c93acdeddb236a52d2852,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
536fb2baa603b0a3beca95431fd27e15fb630674,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
59f76abd6a9b78975746a86efb68d4ef40feac8e,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
206d1b4ad96a589f904f8dc7383bfe7cf68f9a59,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
4c572b27658746d48b85b25fa8aa9c6d94a47bcf,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,True
80ae2988547a9163342117a914b53b6a63487901,PMC,Translation Elongation Factor 1A Facilitates the Assembly of the Tombusvirus Replicase and Stimulates Minus-Strand Synthesis,http://dx.doi.org/10.1371/journal.ppat.1001175,PMC2973826,21079685,CC BY,"Replication of plus-strand RNA viruses depends on host factors that are recruited into viral replicase complexes. Previous studies showed that eukaryotic translation elongation factor (eEF1A) is one of the resident host proteins in the highly purified tombusvirus replicase complex. Using a random library of eEF1A mutants, we identified one mutant that decreased and three mutants that increased Tomato bushy stunt virus (TBSV) replication in a yeast model host. Additional in vitro assays with whole cell extracts prepared from yeast strains expressing the eEF1A mutants demonstrated several functions for eEF1A in TBSV replication: facilitating the recruitment of the viral RNA template into the replicase complex; the assembly of the viral replicase complex; and enhancement of the minus-strand synthesis by promoting the initiation step. These roles for eEF1A are separate from its canonical role in host and viral protein translation, emphasizing critical functions for this abundant cellular protein during TBSV replication.",2010 Nov 4,"['Li, Zhenghe', 'Pogany, Judit', 'Tupman, Steven', 'Esposito, Anthony M.', 'Kinzy, Terri Goss', 'Nagy, Peter D.']",PLoS Pathog,,,True
4fb69ac9627ce50a185d8476c9a0cdcd047a9c72,PMC,Translation Elongation Factor 1A Facilitates the Assembly of the Tombusvirus Replicase and Stimulates Minus-Strand Synthesis,http://dx.doi.org/10.1371/journal.ppat.1001175,PMC2973826,21079685,CC BY,"Replication of plus-strand RNA viruses depends on host factors that are recruited into viral replicase complexes. Previous studies showed that eukaryotic translation elongation factor (eEF1A) is one of the resident host proteins in the highly purified tombusvirus replicase complex. Using a random library of eEF1A mutants, we identified one mutant that decreased and three mutants that increased Tomato bushy stunt virus (TBSV) replication in a yeast model host. Additional in vitro assays with whole cell extracts prepared from yeast strains expressing the eEF1A mutants demonstrated several functions for eEF1A in TBSV replication: facilitating the recruitment of the viral RNA template into the replicase complex; the assembly of the viral replicase complex; and enhancement of the minus-strand synthesis by promoting the initiation step. These roles for eEF1A are separate from its canonical role in host and viral protein translation, emphasizing critical functions for this abundant cellular protein during TBSV replication.",2010 Nov 4,"['Li, Zhenghe', 'Pogany, Judit', 'Tupman, Steven', 'Esposito, Anthony M.', 'Kinzy, Terri Goss', 'Nagy, Peter D.']",PLoS Pathog,,,False
7e27930203695841117f05b4e80661b8e317c1b6,PMC,Translation Elongation Factor 1A Facilitates the Assembly of the Tombusvirus Replicase and Stimulates Minus-Strand Synthesis,http://dx.doi.org/10.1371/journal.ppat.1001175,PMC2973826,21079685,CC BY,"Replication of plus-strand RNA viruses depends on host factors that are recruited into viral replicase complexes. Previous studies showed that eukaryotic translation elongation factor (eEF1A) is one of the resident host proteins in the highly purified tombusvirus replicase complex. Using a random library of eEF1A mutants, we identified one mutant that decreased and three mutants that increased Tomato bushy stunt virus (TBSV) replication in a yeast model host. Additional in vitro assays with whole cell extracts prepared from yeast strains expressing the eEF1A mutants demonstrated several functions for eEF1A in TBSV replication: facilitating the recruitment of the viral RNA template into the replicase complex; the assembly of the viral replicase complex; and enhancement of the minus-strand synthesis by promoting the initiation step. These roles for eEF1A are separate from its canonical role in host and viral protein translation, emphasizing critical functions for this abundant cellular protein during TBSV replication.",2010 Nov 4,"['Li, Zhenghe', 'Pogany, Judit', 'Tupman, Steven', 'Esposito, Anthony M.', 'Kinzy, Terri Goss', 'Nagy, Peter D.']",PLoS Pathog,,,False
a0b861ad1d27b6dd11fe48aa245996a8d9bd01ec,PMC,Translation Elongation Factor 1A Facilitates the Assembly of the Tombusvirus Replicase and Stimulates Minus-Strand Synthesis,http://dx.doi.org/10.1371/journal.ppat.1001175,PMC2973826,21079685,CC BY,"Replication of plus-strand RNA viruses depends on host factors that are recruited into viral replicase complexes. Previous studies showed that eukaryotic translation elongation factor (eEF1A) is one of the resident host proteins in the highly purified tombusvirus replicase complex. Using a random library of eEF1A mutants, we identified one mutant that decreased and three mutants that increased Tomato bushy stunt virus (TBSV) replication in a yeast model host. Additional in vitro assays with whole cell extracts prepared from yeast strains expressing the eEF1A mutants demonstrated several functions for eEF1A in TBSV replication: facilitating the recruitment of the viral RNA template into the replicase complex; the assembly of the viral replicase complex; and enhancement of the minus-strand synthesis by promoting the initiation step. These roles for eEF1A are separate from its canonical role in host and viral protein translation, emphasizing critical functions for this abundant cellular protein during TBSV replication.",2010 Nov 4,"['Li, Zhenghe', 'Pogany, Judit', 'Tupman, Steven', 'Esposito, Anthony M.', 'Kinzy, Terri Goss', 'Nagy, Peter D.']",PLoS Pathog,,,False
c75583662971c89996bdfa312d5c80f43c9950b2,PMC,Translation Elongation Factor 1A Facilitates the Assembly of the Tombusvirus Replicase and Stimulates Minus-Strand Synthesis,http://dx.doi.org/10.1371/journal.ppat.1001175,PMC2973826,21079685,CC BY,"Replication of plus-strand RNA viruses depends on host factors that are recruited into viral replicase complexes. Previous studies showed that eukaryotic translation elongation factor (eEF1A) is one of the resident host proteins in the highly purified tombusvirus replicase complex. Using a random library of eEF1A mutants, we identified one mutant that decreased and three mutants that increased Tomato bushy stunt virus (TBSV) replication in a yeast model host. Additional in vitro assays with whole cell extracts prepared from yeast strains expressing the eEF1A mutants demonstrated several functions for eEF1A in TBSV replication: facilitating the recruitment of the viral RNA template into the replicase complex; the assembly of the viral replicase complex; and enhancement of the minus-strand synthesis by promoting the initiation step. These roles for eEF1A are separate from its canonical role in host and viral protein translation, emphasizing critical functions for this abundant cellular protein during TBSV replication.",2010 Nov 4,"['Li, Zhenghe', 'Pogany, Judit', 'Tupman, Steven', 'Esposito, Anthony M.', 'Kinzy, Terri Goss', 'Nagy, Peter D.']",PLoS Pathog,,,False
8a0a29d6e80385dfdfd8ea1a301cc15e430bb11e,PMC,Zn(2+) Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture,http://dx.doi.org/10.1371/journal.ppat.1001176,PMC2973827,21079686,CC BY,"Increasing the intracellular Zn(2+) concentration with zinc-ionophores like pyrithione (PT) can efficiently impair the replication of a variety of RNA viruses, including poliovirus and influenza virus. For some viruses this effect has been attributed to interference with viral polyprotein processing. In this study we demonstrate that the combination of Zn(2+) and PT at low concentrations (2 µM Zn(2+) and 2 µM PT) inhibits the replication of SARS-coronavirus (SARS-CoV) and equine arteritis virus (EAV) in cell culture. The RNA synthesis of these two distantly related nidoviruses is catalyzed by an RNA-dependent RNA polymerase (RdRp), which is the core enzyme of their multiprotein replication and transcription complex (RTC). Using an activity assay for RTCs isolated from cells infected with SARS-CoV or EAV—thus eliminating the need for PT to transport Zn(2+) across the plasma membrane—we show that Zn(2+) efficiently inhibits the RNA-synthesizing activity of the RTCs of both viruses. Enzymatic studies using recombinant RdRps (SARS-CoV nsp12 and EAV nsp9) purified from E. coli subsequently revealed that Zn(2+) directly inhibited the in vitro activity of both nidovirus polymerases. More specifically, Zn(2+) was found to block the initiation step of EAV RNA synthesis, whereas in the case of the SARS-CoV RdRp elongation was inhibited and template binding reduced. By chelating Zn(2+) with MgEDTA, the inhibitory effect of the divalent cation could be reversed, which provides a novel experimental tool for in vitro studies of the molecular details of nidovirus replication and transcription.",2010 Nov 4,"['te Velthuis, Aartjan J. W.', 'van den Worm, Sjoerd H. E.', 'Sims, Amy C.', 'Baric, Ralph S.', 'Snijder, Eric J.', 'van Hemert, Martijn J.']",PLoS Pathog,,,True
6daca390ad9b7e330f843410f2218f0b27915cd0,PMC,The calculation of information and organismal complexity,http://dx.doi.org/10.1186/1745-6150-5-59,PMC2973933,20937149,CC BY,"BACKGROUND: It is difficult to measure precisely the phenotypic complexity of living organisms. Here we propose a method to calculate the minimal amount of genomic information needed to construct organism (effective information) as a measure of organismal complexity, by using permutation and combination formulas and Shannon's information concept. RESULTS: The results demonstrate that the calculated information correlates quite well with the intuitive organismal phenotypic complexity defined by traditional taxonomy and evolutionary theory. From viruses to human beings, the effective information gradually increases, from thousands of bits to hundreds of millions of bits. The simpler the organism is, the less the information; the more complex the organism, the more the information. About 13% of human genome is estimated as effective information or functional sequence. CONCLUSIONS: The effective information can be used as a quantitative measure of phenotypic complexity of living organisms and also as an estimate of functional fraction of genome. REVIEWERS: This article was reviewed by Dr. Lavanya Kannan (nominated by Dr. Arcady Mushegian), Dr. Chao Chen, and Dr. ED Rietman (nominated by Dr. Marc Vidal).",2010 Oct 12,"['Jiang, Yun', 'Xu, Cunshuan']",Biol Direct,,,True
e7a8dfcde06b70cb86b30074d9008635252d6301,PMC,Computer aided selection of candidate vaccine antigens,http://dx.doi.org/10.1186/1745-7580-6-S2-S1,PMC2981880,21067543,CC BY,"Immunoinformatics is an emergent branch of informatics science that long ago pullulated from the tree of knowledge that is bioinformatics. It is a discipline which applies informatic techniques to problems of the immune system. To a great extent, immunoinformatics is typified by epitope prediction methods. It has found disappointingly limited use in the design and discovery of new vaccines, which is an area where proper computational support is generally lacking. Most extant vaccines are not based around isolated epitopes but rather correspond to chemically-treated or attenuated whole pathogens or correspond to individual proteins extract from whole pathogens or correspond to complex carbohydrate. In this chapter we attempt to review what progress there has been in an as-yet-underexplored area of immunoinformatics: the computational discovery of whole protein antigens. The effective development of antigen prediction methods would significantly reduce the laboratory resource required to identify pathogenic proteins as candidate subunit vaccines. We begin our review by placing antigen prediction firmly into context, exploring the role of reverse vaccinology in the design and discovery of vaccines. We also highlight several competing yet ultimately complementary methodological approaches: sub-cellular location prediction, identifying antigens using sequence similarity, and the use of sophisticated statistical approaches for predicting the probability of antigen characteristics. We end by exploring how a systems immunomics approach to the prediction of immunogenicity would prove helpful in the prediction of antigens.",2010 Nov 3,"['Flower, Darren R', 'Macdonald, Isabel K', 'Ramakrishnan, Kamna', 'Davies, Matthew N', 'Doytchinova, Irini A']",Immunome Res,,,True
816fc25c7f0997c17db295c0a77b18b1a2375338,PMC,Models of RNA virus evolution and their roles in vaccine design,http://dx.doi.org/10.1186/1745-7580-6-S2-S5,PMC2981881,21067547,CC BY,"Viruses are fast evolving pathogens that continuously adapt to the highly variable environments they live and reproduce in. Strategies devoted to inhibit virus replication and to control their spread among hosts need to cope with these extremely heterogeneous populations and with their potential to avoid medical interventions. Computational techniques such as phylogenetic methods have broadened our picture of viral evolution both in time and space, and mathematical modeling has contributed substantially to our progress in unraveling the dynamics of virus replication, fitness, and virulence. Integration of multiple computational and mathematical approaches with experimental data can help to predict the behavior of viral pathogens and to anticipate their escape dynamics. This piece of information plays a critical role in some aspects of vaccine development, such as viral strain selection for vaccinations or rational attenuation of viruses. Here we review several aspects of viral evolution that can be addressed quantitatively, and we discuss computational methods that have the potential to improve vaccine design.",2010 Nov 3,"['Ojosnegros, Samuel', 'Beerenwinkel, Niko']",Immunome Res,,,True
2e6797f37268c2339ab73addc0e9ef77efd3c557,PMC,Pro-inflammatory cytokines derived from West Nile virus (WNV)-infected SK-N-SH cells mediate neuroinflammatory markers and neuronal death,http://dx.doi.org/10.1186/1742-2094-7-73,PMC2984415,21034511,CC BY,"BACKGROUND: WNV-associated encephalitis (WNVE) is characterized by increased production of pro-inflammatory mediators, glial cells activation and eventual loss of neurons. WNV infection of neurons is rapidly progressive and destructive whereas infection of non-neuronal brain cells is limited. However, the role of neurons and pathological consequences of pro-inflammatory cytokines released as a result of WNV infection is unclear. Therefore, the objective of this study was to examine the role of key cytokines secreted by WNV-infected neurons in mediating neuroinflammatory markers and neuronal death. METHODS: A transformed human neuroblastoma cell line, SK-N-SH, was infected with WNV at multiplicity of infection (MOI)-1 and -5, and WNV replication kinetics and expression profile of key pro-inflammatory cytokines were analyzed by plaque assay, qRT-PCR, and ELISA. Cell death was measured in SK-N-SH cell line in the presence and absence of neutralizing antibodies against key pro-inflammatory cytokines using cell viability assay, TUNEL and flow cytometry. Further, naïve primary astrocytes were treated with UV-inactivated supernatant from mock- and WNV-infected SK-N-SH cell line and the activation of astrocytes was measured using flow cytometry and ELISA. RESULTS: WNV-infected SK-N-SH cells induced the expression of IL-1β, -6, -8, and TNF-α in a dose- and time-dependent manner, which coincided with increase in virus-induced cell death. Treatment of cells with anti-IL-1β or -TNF-α resulted in significant reduction of the neurotoxic effects of WNV. Furthermore treatment of naïve astrocytes with UV-inactivated supernatant from WNV-infected SK-N-SH cell line increased expression of glial fibrillary acidic protein and key inflammatory cytokines. CONCLUSION: Our results for the first time suggest that neurons are one of the potential sources of pro-inflammatory cytokines in WNV-infected brain and these neuron-derived cytokines contribute to WNV-induced neurotoxicity. Moreover, cytokines released from neurons also mediate the activation of astrocytes. Our data define specific role(s) of WNV-induced pro-inflammatory cytokines and provide a framework for the development of anti-inflammatory drugs as much-needed therapeutic interventions to limit symptoms associated with WNVE.",2010 Oct 31,"['Kumar, Mukesh', 'Verma, Saguna', 'Nerurkar, Vivek R']",J Neuroinflammation,,,True
fadf1a77d8e94ac8611eb79cf4d0da59872d72bb,PMC,Failure of Fluid Absorption in the Endolymphatic Sac Initiates Cochlear Enlargement that Leads to Deafness in Mice Lacking Pendrin Expression,http://dx.doi.org/10.1371/journal.pone.0014041,PMC2984494,21103348,CC BY,"Mutations of SLC26A4 are among the most prevalent causes of hereditary deafness. Deafness in the corresponding mouse model, Slc26a4(−/−), results from an abnormally enlarged cochlear lumen. The goal of this study was to determine whether the cochlear enlargement originates with defective cochlear fluid transport or with a malfunction of fluid transport in the connected compartments, which are the vestibular labyrinth and the endolymphatic sac. Embryonic inner ears from Slc26a4(+/−) and Slc26a4(−/−) mice were examined by confocal microscopy ex vivo or after 2 days of organ culture. Culture allowed observations of intact, ligated or partially resected inner ears. Cochlear lumen formation was found to begin at the base of the cochlea between embryonic day (E) 13.5 and 14.5. Enlargement was immediately evident in Slc26a4(−/−) compared to Slc26a4(+/−) mice. In Slc26a4(+/−) and Slc26a4(−/−) mice, separation of the cochlea from the vestibular labyrinth by ligation at E14.5 resulted in a reduced cochlear lumen. Resection of the endolymphatic sacs at E14.5 led to an enlarged cochlear lumen in Slc26a4(+/−) mice but caused no further enlargement of the already enlarged cochlear lumen in Slc26a4(−/−) mice. Ligation or resection performed later, at E17.5, did not alter the cochlea lumen. In conclusion, the data suggest that cochlear lumen formation is initiated by fluid secretion in the vestibular labyrinth and temporarily controlled by fluid absorption in the endolymphatic sac. Failure of fluid absorption in the endolymphatic sac due to lack of Slc26a4 expression appears to initiate cochlear enlargement in mice, and possibly humans, lacking functional Slc26a4 expression.",2010 Nov 17,"['Kim, Hyoung-Mi', 'Wangemann, Philine']",PLoS One,,,True
4be572af41fbf94759bf8872ff257fa0f632dca0,PMC,Network Analysis of Global Influenza Spread,http://dx.doi.org/10.1371/journal.pcbi.1001005,PMC2987833,21124942,CC BY,"Although vaccines pose the best means of preventing influenza infection, strain selection and optimal implementation remain difficult due to antigenic drift and a lack of understanding global spread. Detecting viral movement by sequence analysis is complicated by skewed geographic and seasonal distributions in viral isolates. We propose a probabilistic method that accounts for sampling bias through spatiotemporal clustering and modeling regional and seasonal transmission as a binomial process. Analysis of H3N2 not only confirmed East-Southeast Asia as a source of new seasonal variants, but also increased the resolution of observed transmission to a country level. H1N1 data revealed similar viral spread from the tropics. Network analysis suggested China and Hong Kong as the origins of new seasonal H3N2 strains and the United States as a region where increased vaccination would maximally disrupt global spread of the virus. These techniques provide a promising methodology for the analysis of any seasonal virus, as well as for the continued surveillance of influenza.",2010 Nov 18,"['Chan, Joseph', 'Holmes, Antony', 'Rabadan, Raul']",PLoS Comput Biol,,,True
b1ec83bddfe11fc5f176972ca4ae358b4f46c79f,PMC,Potent and persistent antibody responses against the receptor-binding domain of SARS-CoV spike protein in recovered patients,http://dx.doi.org/10.1186/1743-422X-7-299,PMC2988023,21047436,CC BY,"BACKGROUND: The spike (S) protein of SARS-CoV not only mediates receptor-binding but also induces neutralizing antibodies. We previously identified the receptor-binding domain (RBD) of S protein as a major target of neutralizing antibodies in animal models and thus proposed a RBD-based vaccine. However, the antigenicity and immunogenicity of RBD in humans need to be characterized. RESULTS: Two panels of serum samples from recovered SARS patients were included and the antibody responses against the RBD were measured by ELISA and micro-neutralization assays. We found that the RBD of S protein induced potent antibody responses in the recovered SARS patients and RBD-specific antibodies could persist at high titers over three year follow-up. Furthermore, affinity purified anti-RBD antibodies possessed robust neutralizing activity. CONCLUSION: The RBD of SARS-CoV is highly immunogenic in humans and mediates protective responses and RBD-based vaccines and diagnostic approaches can be further developed.",2010 Nov 4,"['Cao, Zhiliang', 'Liu, Lifeng', 'Du, Lanying', 'Zhang, Chao', 'Jiang, Shibo', 'Li, Taisheng', 'He, Yuxian']",Virol J,,,True
357a008270023e621d758ada372b14e676edb782,PMC,Facing the threat of influenza pandemic - roles of and implications to general practitioners,http://dx.doi.org/10.1186/1471-2458-10-661,PMC2988738,21044300,CC BY,"The 2009 pandemic of H1N1 influenza, compounded with seasonal influenza, posed a global challenge. Despite the announcement of post-pandemic period on 10 August 2010 by theWHO, H1N1 (2009) virus would continue to circulate as a seasonal virus for some years and national health authorities should remain vigilant due to unpredictable behaviour of the virus. Majority of the world population is living in countries with inadequate resources to purchase vaccines and stockpile antiviral drugs. Basic hygienic measures such as wearing face masks and the hygienic practice of hand washing could reduce the spread of the respiratory viruses. However, the imminent issue is translating these measures into day-to-day practice. The experience from Severe Acute Respiratory Syndrome (SARS) in Hong Kong has shown that general practitioners (GPs) were willing to discharge their duties despite risks of getting infected themselves. SARS event has highlighted the inadequate interface between primary and secondary care and valuable health care resources were thus inappropriately matched to community needs. There are various ways for GPs to contribute in combating the influenza pandemic. They are prompt in detecting and monitoring epidemics and mini-epidemics of viral illnesses in the community. They can empower and raise the health literacy of the community such as advocating personal hygiene and other precautious measures. GPs could also assist in the development of protocols for primary care management of patients with flu-like illnesses and conduct clinical audits on the standards of preventive and treatment measures. GPs with adequate liaison with public health agencies would facilitate early diagnosis of patients with influenza. In this article, we summarise the primary care actions for phases 4-6 of the pandemic. We shall discuss the novel roles of GPs as alternative source of health care for patients who would otherwise be cared for in the secondary care level. The health care system would thus remain sustainable during the public health crisis.",2010 Nov 2,"['Lee, Albert', 'Chuh, Antonio AT']",BMC Public Health,,,True
9f27a960236a99c8b1dc60e71e111257a1d5e862,PMC,Sequencing of DC-SIGN promoter indicates an association between promoter variation and risk of nasopharyngeal carcinoma in cantonese,http://dx.doi.org/10.1186/1471-2350-11-161,PMC2989958,21067616,CC BY,BACKGROUND: The dendritic cell-specific intercellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) is an important pathogen recognition receptor of the innate immune system. DC-SIGN promoter variants play important role in the susceptibility to various infectious diseases. Nasopharyngeal carcinoma (NPC) is a malignancy that is common in southern China and whether DC-SIGN promoter variants have effects on susceptibility to NPC is still unknown. The aim of this study is to ascertain the potential involvement of DC-SIGN promoter single nucleotide polymorphisms (SNPs) in NPC susceptibility. METHODS: We conducted a case control study based on Cantonese population including 444 NPC patients and 464 controls matched on age and sex. The 1041 bp of DC-SIGN promoter region was directly sequenced for all samples. Sequence alignment and SNP search were inspected using DNAStar analysis programs and haplotype frequencies were estimated in Haploview V 4.0. The associations between the SNPs and the risk of NPC were analyzed using chi-square test and non-conditional logistic regression analysis with SPSS 13.0 software. RESULTS: A total of six variants were observed in the DC-SIGN promoter region and DC-SIGN -139 GG and -939 AA were significantly associated with NPC risk with adjusted Odds Ratios (ORs) of 2.10 (95% confidence interval [CI] = 1.23-3.59; P = 0.006) and 2.52 (1.29-4.93; P = 0.007) respectively and subjects carrying the risk allele DC-SIGN -871 G had 1.47-fold (95% CI = 1.14-1.90) increased risks of developing NPC (P = 0.003). Haplotype analysis revealed that h1 'AAAG' was significantly associated with protection against NPC (OR = 0.69; P = 0.0002) and the association was still significant when using 1000 permutation test runs (P = 0.001). CONCLUSIONS: Our study indicated that DC-SIGN promoter variants appear to be involved in the susceptibility to NPC and the detailed mechanism of this effect need further studies.,2010 Nov 11,"['Xu, Ya-Fei', 'Liu, Wan-Li', 'Dong, Ju-Qin', 'Liu, Wen-Sheng', 'Feng, Qi-Sheng', 'Chen, Li-Zhen', 'Zeng, Yi-Xin', 'Zeng, Mu-Sheng', 'Jia, Wei-Hua']",BMC Med Genet,,,True
fd5e3020671499cde830bd25de618009ece0af13,PMC,Antiviral and Neuroprotective Role of Octaguanidinium Dendrimer-Conjugated Morpholino Oligomers in Japanese Encephalitis,http://dx.doi.org/10.1371/journal.pntd.0000892,PMC2990691,21124882,CC BY,"BACKGROUND: Japanese encephalitis (JE), caused by a mosquito-borne flavivirus, is endemic to the entire south-east Asian and adjoining regions. Currently no therapeutic interventions are available for JE, thereby making it one of the most dreaded encephalitides in the world. An effective way to counter the virus would be to inhibit viral replication by using anti-sense molecules directed against the viral genome. Octaguanidinium dendrimer-conjugated Morpholino (or Vivo-Morpholino) are uncharged anti-sense oligomers that can enter cells of living organisms by endocytosis and subsequently escape from endosomes into the cytosol/nuclear compartment of cells. We hypothesize that Vivo-Morpholinos generated against specific regions of 3′ or 5′ untranslated regions of JEV genome, when administered in an experimental model of JE, will have significant antiviral and neuroprotective effect. METHODOLOGY/PRINCIPAL FINDINGS: Mice were infected with JEV (GP78 strain) followed by intraperitoneal administration of Morpholinos (5 mg/kg body weight) daily for up to five treatments. Survivability of the animals was monitored for 15 days (or until death) following which they were sacrificed and their brains were processed either for immunohistochemical staining or protein extraction. Plaque assay and immunoblot analysis performed from brain homogenates showed reduced viral load and viral protein expression, resulting in greater survival of infected animals. Neuroprotective effect was observed by thionin staining of brain sections. Cytokine bead array showed reduction in the levels of proinflammatory cytokines in brain following Morpholino treatment, which were elevated after infection. This corresponded to reduced microglial activation in brain. Oxidative stress was reduced and certain stress-related signaling molecules were found to be positively modulated following Morpholino treatment. In vitro studies also showed that there was decrease in infective viral particle production following Morpholino treatment. CONCLUSIONS/SIGNIFICANCE: Administration of Vivo-Morpholino effectively resulted in increased survival of animals and neuroprotection in a murine model of JE. Hence, these oligomers represent a potential antiviral agent that merits further evaluation.",2010 Nov 23,"['Nazmi, Arshed', 'Dutta, Kallol', 'Basu, Anirban']",PLoS Negl Trop Dis,,,True
bbd8195f35ba4648be5eb649a3038f7485b7a71e,PMC,"General hospital staff worries, perceived sufficiency of information and associated psychological distress during the A/H1N1 influenza pandemic",http://dx.doi.org/10.1186/1471-2334-10-322,PMC2990753,21062471,CC BY,"BACKGROUND: Health care workers (HCWs) presented frequent concerns regarding their health and their families' health and high levels of psychological distress during previous disease outbreaks, such as the SARS outbreak, which was associated with social isolation and intentional absenteeism. We aimed to assess HCWs concerns and anxiety, perceived sufficiency of information, and intended behavior during the recent A/H1N1 influenza pandemic and their associations with psychological distress. METHOD: Between September 1(st )and 30(th), 2009, 469 health-care workers (HCWs) of a tertiary teaching hospital completed a 20-item questionnaire regarding concerns and worries about the new A/H1N1 influenza pandemic, along with Cassileth's Information Styles Questionnaire (part-I) and the GHQ-28. RESULTS: More than half of the present study's HCWs (56.7%) reported they were worried about the A/H1N1 influenza pandemic, their degree of anxiety being moderately high (median 6/9). The most frequent concern was infection of family and friends and the health consequences of the disease (54.9%). The perceived risk of being infected was considered moderately high (median 6/9). Few HCWs (6.6%) had restricted their social contacts and fewer (3.8%) felt isolated by their family members and friends because of their hospital work, while a low percentage (4.3%) indented to take a leave to avoid infection. However, worry and degree of worry were significantly associated with intended absenteeism (p < 0.0005), restriction of social contacts (p < 0.0005), and psychological distress (p = 0.036). Perceived sufficiency of information about several aspects of the A/H1N1 influenza was moderately high, and the overall information about the A/H1N1 influenza was considered clear (median 7.4/9). Also, perceived sufficiency of information for the prognosis of the infection was significantly independently associated with the degree of worry about the pandemic (p = 0.008). CONCLUSIONS: A significant proportion of HCWs experienced moderately high anxiety about the pandemic, and their degree of worry was an independent correlate of psychological distress. Since perceived sufficiency of information about the A/H1N1 influenza prognosis was associated with reduced degree of worry, hospital managers and consultation-liaison psychiatry services should try to provide for HCWs' need for information, in order to offer favourable working conditions in times of extreme distress, such as the current and future pandemics.",2010 Nov 9,"['Goulia, Panagiota', 'Mantas, Christos', 'Dimitroula, Danai', 'Mantis, Dimitrios', 'Hyphantis, Thomas']",BMC Infect Dis,,,True
248e6ce743867edebd9fb8d241a56f542732888a,PMC,Antiviral Lead Compounds from Marine Sponges,http://dx.doi.org/10.3390/md8102619,PMC2992996,21116410,CC BY,"Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment. These bioactive molecules are often secondary metabolites, whose main function is to enable and/or modulate cellular communication and defense. They are usually produced by functional enzyme clusters in sponges and/or their associated symbiotic microorganisms. Natural product lead compounds from sponges have often been found to be promising pharmaceutical agents. Several of them have successfully been approved as antiviral agents for clinical use or have been advanced to the late stages of clinical trials. Most of these drugs are used for the treatment of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due to the discovery of new types of viruses and emergence of drug resistant strains, it is necessary to develop new antiviral lead compounds continuously. Several sponge derived antiviral lead compounds which are hopedto be developed as future drugs are discussed in this review. Supply problems are usually the major bottleneck to the development of these compounds as drugs during clinical trials. However advances in the field of metagenomics and high throughput microbial cultivation has raised the possibility that these techniques could lead to the cost-effective large scale production of such compounds. Perspectives on biotechnological methods with respect to marine drug development are also discussed.",2010 Oct 11,"['Sagar, Sunil', 'Kaur, Mandeep', 'Minneman, Kenneth P.']",Mar Drugs,,,True
e806597d3525be5b55b7bd8812217c2e53bced9f,PMC,A Functional Henipavirus Envelope Glycoprotein Pseudotyped Lentivirus Assay System,http://dx.doi.org/10.1186/1743-422X-7-312,PMC2994542,21073718,CC BY,"BACKGROUND: Hendra virus (HeV) and Nipah virus (NiV) are newly emerged zoonotic paramyxoviruses discovered during outbreaks in Queensland, Australia in 1994 and peninsular Malaysia in 1998/9 respectively and classified within the new Henipavirus genus. Both viruses can infect a broad range of mammalian species causing severe and often-lethal disease in humans and animals, and repeated outbreaks continue to occur. Extensive laboratory studies on the host cell infection stage of HeV and NiV and the roles of their envelope glycoproteins have been hampered by their highly pathogenic nature and restriction to biosafety level-4 (BSL-4) containment. To circumvent this problem, we have developed a henipavirus envelope glycoprotein pseudotyped lentivirus assay system using either a luciferase gene or green fluorescent protein (GFP) gene encoding human immunodeficiency virus type-1 (HIV-1) genome in conjunction with the HeV and NiV fusion (F) and attachment (G) glycoproteins. RESULTS: Functional retrovirus particles pseudotyped with henipavirus F and G glycoproteins displayed proper target cell tropism and entry and infection was dependent on the presence of the HeV and NiV receptors ephrinB2 or B3 on target cells. The functional specificity of the assay was confirmed by the lack of reporter-gene signals when particles bearing either only the F or only G glycoprotein were prepared and assayed. Virus entry could be specifically blocked when infection was carried out in the presence of a fusion inhibiting C-terminal heptad (HR-2) peptide, a well-characterized, cross-reactive, neutralizing human mAb specific for the henipavirus G glycoprotein, and soluble ephrinB2 and B3 receptors. In addition, the utility of the assay was also demonstrated by an examination of the influence of the cytoplasmic tail of F in its fusion activity and incorporation into pseudotyped virus particles by generating and testing a panel of truncation mutants of NiV and HeV F. CONCLUSIONS: Together, these results demonstrate that a specific henipavirus entry assay has been developed using NiV or HeV F and G glycoprotein pseudotyped reporter-gene encoding retrovirus particles. This assay can be conducted safely under BSL-2 conditions and will be a useful tool for measuring henipavirus entry and studying F and G glycoprotein function in the context of virus entry, as well as in assaying and characterizing neutralizing antibodies and virus entry inhibitors.",2010 Nov 12,"['Khetawat, Dimple', 'Broder, Christopher C']",Virol J,,,True
b9881ca556b8d6e74c2fe3b9c2195429fcb0d09d,PMC,H1N1pdm Influenza Infection in Hospitalized Cancer Patients: Clinical Evolution and Viral Analysis,http://dx.doi.org/10.1371/journal.pone.0014158,PMC2994772,21152402,CC0,"BACKGROUND: The novel influenza A pandemic virus (H1N1pdm) caused considerable morbidity and mortality worldwide in 2009. The aim of the present study was to evaluate the clinical course, duration of viral shedding, H1N1pdm evolution and emergence of antiviral resistance in hospitalized cancer patients with severe H1N1pdm infections during the winter of 2009 in Brazil. METHODS: We performed a prospective single-center cohort study in a cancer center in Rio de Janeiro, Brazil. Hospitalized patients with cancer and a confirmed diagnosis of influenza A H1N1pdm were evaluated. The main outcome measures in this study were in-hospital mortality, duration of viral shedding, viral persistence and both functional and molecular analyses of H1N1pdm susceptibility to oseltamivir. RESULTS: A total of 44 hospitalized patients with suspected influenza-like illness were screened. A total of 24 had diagnosed H1N1pdm infections. The overall hospital mortality in our cohort was 21%. Thirteen (54%) patients required intensive care. The median age of the studied cohort was 14.5 years (3–69 years). Eighteen (75%) patients had received chemotherapy in the previous month, and 14 were neutropenic at the onset of influenza. A total of 10 patients were evaluated for their duration of viral shedding, and 5 (50%) displayed prolonged viral shedding (median 23, range = 11–63 days); however, this was not associated with the emergence of a resistant H1N1pdm virus. Viral evolution was observed in sequentially collected samples. CONCLUSIONS: Prolonged influenza A H1N1pdm shedding was observed in cancer patients. However, oseltamivir resistance was not detected. Taken together, our data suggest that severely ill cancer patients may constitute a pandemic virus reservoir with major implications for viral propagation.",2010 Nov 30,"['Souza, Thiago Moreno L.', 'Salluh, Jorge I. F.', 'Bozza, Fernando A.', 'Mesquita, Milene', 'Soares, Márcio', 'Motta, Fernando C.', 'Pitrowsky, Melissa Tassano', 'de Lourdes Oliveira, Maria', 'Mishin, Vasiliy P.', 'Gubareva, Larissa V.', 'Whitney, Anne', 'Rocco, Sandra Amaral', 'Gonçalves, Vânia Maria C.', 'Marques, Venceslaine Prado', 'Velasco, Eduardo', 'Siqueira, Marilda M.']",PLoS One,,,True
f4f804bac7b32c84ad6572776df684df2a2e5fda,PMC,Livestock Drugs and Disease: The Fatal Combination behind Breeding Failure in Endangered Bearded Vultures,http://dx.doi.org/10.1371/journal.pone.0014163,PMC2994777,21152405,CC BY,"There is increasing concern about the impact of veterinary drugs and livestock pathogens as factors damaging wildlife health, especially of threatened avian scavengers feeding upon medicated livestock carcasses. We conducted a comprehensive study of failed eggs and dead nestlings in bearded vultures (Gypaetus barbatus) to attempt to elucidate the proximate causes of breeding failure behind the recent decline in productivity in the Spanish Pyrenees. We found high concentrations of multiple veterinary drugs, primarily fluoroquinolones, in most failed eggs and nestlings, associated with multiple internal organ damage and livestock pathogens causing disease, especially septicaemia by swine pathogens and infectious bursal disease. The combined impact of drugs and disease as stochastic factors may result in potentially devastating effects exacerbating an already high risk of extinction and should be considered in current conservation programs for bearded vultures and other scavenger species, especially in regards to dangerous veterinary drugs and highly pathogenic poultry viruses.",2010 Nov 30,"['Blanco, Guillermo', 'Lemus, Jesús A.']",PLoS One,,,True
268d325d7a8003c4b0474e6a605d6655ab370b6f,PMC,Contact Heterogeneity and Phylodynamics: How Contact Networks Shape Parasite Evolutionary Trees,http://dx.doi.org/10.1155/2011/238743,PMC2995904,21151699,CC BY,"The inference of population dynamics from molecular sequence data is becoming an important new method for the surveillance of infectious diseases. Here, we examine how heterogeneity in contact shapes the genealogies of parasitic agents. Using extensive simulations, we find that contact heterogeneity can have a strong effect on how the structure of genealogies reflects epidemiologically relevant quantities such as the proportion of a population that is infected. Comparing the simulations to BEAST reconstructions, we also find that contact heterogeneity can increase the number of sequence isolates required to estimate these quantities over the course of an epidemic. Our results suggest that data about contact-network structure will be required in addition to sequence data for accurate estimation of a parasitic agent's genealogy. We conclude that network models will be important for progress in this area.",2011 Dec 1,"[""O'Dea, Eamon B."", 'Wilke, Claus O.']",Interdiscip Perspect Infect Dis,,,True
97e07d83db421faee2a7a42a0e2c8a117c08b016,PMC,Light whole genome sequence for SNP discovery across domestic cat breeds,http://dx.doi.org/10.1186/1471-2164-11-406,PMC2996934,20576142,CC BY,"BACKGROUND: The domestic cat has offered enormous genomic potential in the veterinary description of over 250 hereditary disease models as well as the occurrence of several deadly feline viruses (feline leukemia virus -- FeLV, feline coronavirus -- FECV, feline immunodeficiency virus - FIV) that are homologues to human scourges (cancer, SARS, and AIDS respectively). However, to realize this bio-medical potential, a high density single nucleotide polymorphism (SNP) map is required in order to accomplish disease and phenotype association discovery. DESCRIPTION: To remedy this, we generated 3,178,297 paired fosmid-end Sanger sequence reads from seven cats, and combined these data with the publicly available 2X cat whole genome sequence. All sequence reads were assembled together to form a 3X whole genome assembly allowing the discovery of over three million SNPs. To reduce potential false positive SNPs due to the low coverage assembly, a low upper-limit was placed on sequence coverage and a high lower-limit on the quality of the discrepant bases at a potential variant site. In all domestic cats of different breeds: female Abyssinian, female American shorthair, male Cornish Rex, female European Burmese, female Persian, female Siamese, a male Ragdoll and a female African wildcat were sequenced lightly. We report a total of 964 k common SNPs suitable for a domestic cat SNP genotyping array and an additional 900 k SNPs detected between African wildcat and domestic cats breeds. An empirical sampling of 94 discovered SNPs were tested in the sequenced cats resulting in a SNP validation rate of 99%. CONCLUSIONS: These data provide a large collection of mapped feline SNPs across the cat genome that will allow for the development of SNP genotyping platforms for mapping feline diseases.",2010 Jun 24,"['Mullikin, James C', 'Hansen, Nancy F', 'Shen, Lei', 'Ebling, Heather', 'Donahue, William F', 'Tao, Wei', 'Saranga, David J', 'Brand, Adrianne', 'Rubenfield, Marc J', 'Young, Alice C', 'Cruz, Pedro', 'Driscoll, Carlos', 'David, Victor', 'Al-Murrani, Samer WK', 'Locniskar, Mary F', 'Abrahamsen, Mitchell S', ""O'Brien, Stephen J"", 'Smith, Douglas R', 'Brockman, Jeffrey A']",BMC Genomics,,,True
c7c91a1ce95ce401750cb856d14d48683a0e4fb7,PMC,Hierarchical Clustering Using the Arithmetic-Harmonic Cut: Complexity and Experiments,http://dx.doi.org/10.1371/journal.pone.0014067,PMC2997101,21151943,CC BY,"Clustering, particularly hierarchical clustering, is an important method for understanding and analysing data across a wide variety of knowledge domains with notable utility in systems where the data can be classified in an evolutionary context. This paper introduces a new hierarchical clustering problem defined by a novel objective function we call the arithmetic-harmonic cut. We show that the problem of finding such a cut is [Image: see text]-hard and [Image: see text]-hard but is fixed-parameter tractable, which indicates that although the problem is unlikely to have a polynomial time algorithm (even for approximation), exact parameterized and local search based techniques may produce workable algorithms. To this end, we implement a memetic algorithm for the problem and demonstrate the effectiveness of the arithmetic-harmonic cut on a number of datasets including a cancer type dataset and a corona virus dataset. We show favorable performance compared to currently used hierarchical clustering techniques such as [Image: see text]-Means, Graclus and Normalized-Cut. The arithmetic-harmonic cut metric overcoming difficulties other hierarchal methods have in representing both intercluster differences and intracluster similarities.",2010 Dec 2,"['Rizzi, Romeo', 'Mahata, Pritha', 'Mathieson, Luke', 'Moscato, Pablo']",PLoS One,,,True
621c17ebf69617fe8e330f6c9818880902ee6a97,PMC,Public views of the uk media and government reaction to the 2009 swine flu pandemic,http://dx.doi.org/10.1186/1471-2458-10-697,PMC2998491,21078169,CC BY,"BACKGROUND: The first cases of influenza A/H1N1 (swine flu) were confirmed in the UK on 27th April 2009, after a novel virus first identified in Mexico rapidly evolved into a pandemic. The swine flu outbreak was the first pandemic in more than 40 years and for many, their first encounter with a major influenza outbreak. This study examines public understandings of the pandemic, exploring how people deciphered the threat and perceived they could control the risks. METHODS: Purposive sampling was used to recruit seventy three people (61 women and 12 men) to take part in 14 focus group discussions around the time of the second wave in swine flu cases. RESULTS: These discussions showed that there was little evidence of the public over-reacting, that people believed the threat of contracting swine flu was inevitable, and that they assessed their own self-efficacy for protecting against it to be low. Respondents assessed a greater risk to their health from the vaccine than from the disease. Such findings could have led to apathy about following the UK Governments recommended health protective behaviours, and a sub-optimal level of vaccine uptake. More generally, people were confused about the difference between seasonal influenza and swine flu and their vaccines. CONCLUSIONS: This research suggests a gap in public understandings which could hinder attempts to communicate about novel flu viruses in the future. There was general support for the government's handling of the pandemic, although its public awareness campaign was deemed ineffectual as few people changed their current hand hygiene practices. There was less support for the media who were deemed to have over-reported the swine flu pandemic.",2010 Nov 15,"['Hilton, Shona', 'Smith, Emily']",BMC Public Health,,,True
2cb75a42281bf540c142bec979a4bc66da597a3a,PMC,Association of residential dampness and mold with respiratory tract infections and bronchitis: a meta-analysis,http://dx.doi.org/10.1186/1476-069X-9-72,PMC3000394,21078183,CC BY,"BACKGROUND: Dampness and mold have been shown in qualitative reviews to be associated with a variety of adverse respiratory health effects, including respiratory tract infections. Several published meta-analyses have provided quantitative summaries for some of these associations, but not for respiratory infections. Demonstrating a causal relationship between dampness-related agents, which are preventable exposures, and respiratory tract infections would suggest important new public health strategies. We report the results of quantitative meta-analyses of published studies that examined the association of dampness or mold in homes with respiratory infections and bronchitis. METHODS: For primary studies meeting eligibility criteria, we transformed reported odds ratios (ORs) and confidence intervals (CIs) to the log scale. Both fixed and random effects models were applied to the log ORs and their variances. Most studies contained multiple estimated ORs. Models accounted for the correlation between multiple results within the studies analyzed. One set of analyses was performed with all eligible studies, and another set restricted to studies that controlled for age, gender, smoking, and socioeconomic status. Subgroups of studies were assessed to explore heterogeneity. Funnel plots were used to assess publication bias. RESULTS: The resulting summary estimates of ORs from random effects models based on all studies ranged from 1.38 to 1.50, with 95% CIs excluding the null in all cases. Use of different analysis models and restricting analyses based on control of multiple confounding variables changed findings only slightly. ORs (95% CIs) from random effects models using studies adjusting for major confounding variables were, for bronchitis, 1.45 (1.32-1.59); for respiratory infections, 1.44 (1.31-1.59); for respiratory infections excluding nonspecific upper respiratory infections, 1.50 (1.32-1.70), and for respiratory infections in children or infants, 1.48 (1.33-1.65). Little effect of publication bias was evident. Estimated attributable risk proportions ranged from 8% to 20%. CONCLUSIONS: Residential dampness and mold are associated with substantial and statistically significant increases in both respiratory infections and bronchitis. If these associations were confirmed as causal, effective control of dampness and mold in buildings would prevent a substantial proportion of respiratory infections.",2010 Nov 15,"['Fisk, William J', 'Eliseeva, Ekaterina A', 'Mendell, Mark J']",Environ Health,,,True
e8e766af194b641ae3a9636379a18515c053ae65,PMC,Human monoclonal IgG selection of Plasmodium falciparum for the expression of placental malaria-specific variant surface antigens,http://dx.doi.org/10.1111/j.1365-3024.2009.01097.x,PMC3001033,19493213,CC BY,Pregnancy-associatedPlasmodium falciparum malaria (PAM) is a major cause of morbidity and mortality in African women and their offspring. PAM is characterized by accumulation of infected erythrocytes (IEs) that adhere to chondroitin sulphate A (CSA) in the placental intervillous space. We show here that human monoclonal IgG antibodies with specificity for variant surface antigens (VSA) specifically expressed by CSA-adhering IEs (VSA(PAM)) can be used in vitro to select parasites from nonpregnant donors to express VSA(PAM) and that this selection for VSA(PAM) expression results in preferential transcription of var2csa. The results corroborate current efforts to develop PAM-specific vaccines based on VAR2CSA.,2009 Jun,"['SOERLI, J', 'BARFOD, L', 'LAVSTSEN, T', 'BERNASCONI, N L', 'LANZAVECCHIA, A', 'HVIID, L']",Parasite Immunol,,,True
a64149dbac768a5fac5c4ca620c09c2dea2e2bf0,PMC,"Travel and migration associated infectious diseases morbidity in Europe, 2008",http://dx.doi.org/10.1186/1471-2334-10-330,PMC3001727,21083874,CC BY,"BACKGROUND: Europeans represent the majority of international travellers and clinicians encountering returned patients have an essential role in recognizing, and communicating travel-associated public health risks. METHODS: To investigate the morbidity of travel associated infectious diseases in European travellers, we analysed diagnoses with demographic, clinical and travel-related predictors of disease, in 6957 ill returned travellers who presented in 2008 to EuroTravNet centres with a presumed travel associated condition. RESULTS: Gastro-intestinal (GI) diseases accounted for 33% of illnesses, followed by febrile systemic illnesses (20%), dermatological conditions (12%) and respiratory illnesses (8%). There were 3 deaths recorded; a sepsis caused by Escherichia coli pyelonephritis, a dengue shock syndrome and a Plasmodium falciparum malaria. GI conditions included bacterial acute diarrhea (6.9%), as well as giardiasis and amebasis (2.3%). Among febrile systemic illnesses with identified pathogens, malaria (5.4%) accounted for most cases followed by dengue (1.9%) and others including chikungunya, rickettsial diseases, leptospirosis, brucellosis, Epstein Barr virus infections, tick-borne encephalitis (TBE) and viral hepatitis. Dermatological conditions were dominated by bacterial infections, arthropod bites, cutaneous larva migrans and animal bites requiring rabies post-exposure prophylaxis and also leishmaniasis, myasis, tungiasis and one case of leprosy. Respiratory illness included 112 cases of tuberculosis including cases of multi-drug resistant or extensively drug resistant tuberculosis, 104 cases of influenza like illness, and 5 cases of Legionnaires disease. Sexually transmitted infections (STI) accounted for 0.6% of total diagnoses and included HIV infection and syphilis. A total of 165 cases of potentially vaccine preventable diseases were reported. Purpose of travel and destination specific risk factors was identified for several diagnoses such as Chagas disease in immigrant travellers from South America and P. falciparum malaria in immigrants from sub-Saharan Africa. Travel within Europe was also associated with health risks with distinctive profiles for Eastern and Western Europe. CONCLUSIONS: In 2008, a broad spectrum of travel associated diseases were diagnosed at EuroTravNet core sites. Diagnoses varied according to regions visited by ill travellers. The spectrum of travel associated morbidity also shows that there is a need to dispel the misconception that travel, close to home, in Europe, is without significant health risk.",2010 Nov 17,"['Field, Vanessa', 'Gautret, Philippe', 'Schlagenhauf, Patricia', 'Burchard, Gerd-Dieter', 'Caumes, Eric', 'Jensenius, Mogens', 'Castelli, Francesco', 'Gkrania-Klotsas, Effrossyni', 'Weld, Leisa', 'Lopez-Velez, Rogelio', 'de Vries, Peter', 'von Sonnenburg, Frank', 'Loutan, Louis', 'Parola, Philippe']",BMC Infect Dis,,,True
70f03de789f72ae5b9709cb6bef62c10ab8dcdef,PMC,Flocked nasal swab versus nasopharyngeal aspirate for detection of respiratory tract viruses in immunocompromised adults: a matched comparative study,http://dx.doi.org/10.1186/1471-2334-10-340,PMC3001728,21110854,CC BY,"BACKGROUND: Several studies have compared nasal swabs to the more invasive nasopharyngeal aspirate (NPA) for detection of respiratory viruses. Mostly, the comparisons have been performed on immunocompetent children with upper respiratory tract symptoms. The results range from a relatively poor sensitivity for the swabs to an even higher sensitivity than for the NPA. We aimed to investigate the sensitivity of a flocked nasal swab (fNS) on immunocompromised adults with febrile neutropenia. METHODS: During 16 months, adults with a hematological disorder presenting with febrile neutropenia were enrolled in the study. Paired samples of the fNS and NPA were collected in the outer part of the nasal cavity and the nasopharynx, respectively. The samples were analyzed regarding a panel of 15 respiratory viruses by means of quantitative polymerase chain reaction. Furthermore, as an indirect measure of cell yield by either method, the copy number of the human beta actin gene was also determined. Cohen's kappa was calculated as a measure of agreement of the results obtained from either method. Wilcoxon signed-rank test was used for comparison of cell yield. RESULTS: A total of 98 paired samples from a total of 89 patients were collected. Twenty of the pairs had virus detected in at least one of the specimens; 11 in both, 7 in NPA only, and 2 in fNS only. For the fNS, the overall sensitivity for any virus and for rhinovirus only was 65% and 78%, respectively. NPA was significantly superior to the fNS in collecting epithelial cells. CONCLUSION: We found the overall sensitivity of 65% to be too low to replace NPA with this sampling technique in this patient category.",2010 Nov 26,"['Öhrmalm, Lars', 'Wong, Michelle', 'Rotzén-Östlund, Maria', 'Norbeck, Oscar', 'Broliden, Kristina', 'Tolfvenstam, Thomas']",BMC Infect Dis,,,True
8d8ab6d3f0c6ff09e306c23c87f823f9382ff32e,PMC,Responses of Human Endothelial Cells to Pathogenic and Non-Pathogenic Leptospira Species,http://dx.doi.org/10.1371/journal.pntd.0000918,PMC3001904,21179504,CC BY,"Leptospirosis is a widespread zoonotic infection that primarily affects residents of tropical regions, but causes infections in animals and humans in temperate regions as well. The agents of leptospirosis comprise several members of the genus Leptospira, which also includes non-pathogenic, saprophytic species. Leptospirosis can vary in severity from a mild, non-specific illness to severe disease that includes multi-organ failure and widespread endothelial damage and hemorrhage. To begin to investigate how pathogenic leptospires affect endothelial cells, we compared the responses of two endothelial cell lines to infection by pathogenic versus non-pathogenic leptospires. Microarray analyses suggested that pathogenic L. interrogans and non-pathogenic L. biflexa triggered changes in expression of genes whose products are involved in cellular architecture and interactions with the matrix, but that the changes were in opposite directions, with infection by L. biflexa primarily predicted to increase or maintain cell layer integrity, while L. interrogans lead primarily to changes predicted to disrupt cell layer integrity. Neither bacterial strain caused necrosis or apoptosis of the cells even after prolonged incubation. The pathogenic L. interrogans, however, did result in significant disruption of endothelial cell layers as assessed by microscopy and the ability of the bacteria to cross the cell layers. This disruption of endothelial layer integrity was abrogated by addition of the endothelial protective drug lisinopril at physiologically relevant concentrations. These results suggest that, through adhesion of L. interrogans to endothelial cells, the bacteria may disrupt endothelial barrier function, promoting dissemination of the bacteria and contributing to severe disease manifestations. In addition, supplementing antibiotic therapy with lisinopril or derivatives with endothelial protective activities may decrease the severity of leptospirosis.",2010 Dec 14,"['Martinez-Lopez, Denise G.', 'Fahey, Mark', 'Coburn, Jenifer']",PLoS Negl Trop Dis,,,True
f46d2803581226a9a94026693e95db88e7c70641,PMC,A Porcine Adenovirus with Low Human Seroprevalence Is a Promising Alternative Vaccine Vector to Human Adenovirus 5 in an H5N1 Virus Disease Model,http://dx.doi.org/10.1371/journal.pone.0015301,PMC3002947,21179494,CC BY,"Human adenovirus 5 (AdHu5) vectors are robust vaccine platforms however the presence of naturally-acquired neutralizing antibodies may reduce vector efficacy and potential for re-administration. This study evaluates immune responses and protection following vaccination with a replication-incompetent porcine adenovirus 3 (PAV3) vector as an alternative vaccine to AdHu5 using an avian influenza H5N1 disease model. Vaccine efficacy was evaluated in BALB/c mice following vaccination with different doses of the PAV3 vector expressing an optimized A/Hanoi/30408/2005 H5N1 hemagglutinin antigen (PAV3-HA) and compared with an AdHu5-HA control. PAV3-HA rapidly generated antibody responses, with significant neutralizing antibody titers on day 21, and stronger cellular immune responses detected on day 8, compared to AdHu5-HA. The PAV3-HA vaccine, administered 8 days before challenge, demonstrated improved survival and lower virus load. Evaluation of long-term vaccine efficacy at 12 months post-vaccination showed better protection with the PAV3-HA than with the AdHu5-HA vaccine. Importantly, as opposed to AdHu5, PAV3 vector was not significantly neutralized by human antibodies pooled from over 10,000 individuals. Overall, PAV3-based vector is capable of mediating swift, strong immune responses and offer a promising alternative to AdHu5.",2010 Dec 16,"['Patel, Ami', 'Tikoo, Suresh', 'Kobinger, Gary']",PLoS One,,,True
5bcfcf89e794c73c8d079ddacc6eb7849501b927,PMC,The role of toll-like receptors in acute and chronic lung inflammation,http://dx.doi.org/10.1186/1476-9255-7-57,PMC3003652,21108806,CC BY,"By virtue of its direct contact with the environment, the lung is constantly challenged by infectious and non-infectious stimuli that necessitate a robust yet highly controlled host response coordinated by the innate and adaptive arms of the immune system. Mammalian Toll-like receptors (TLRs) function as crucial sentinels of microbial and non-infectious antigens throughout the respiratory tract and mediate host innate immunity. Selective induction of inflammatory responses to harmful environmental exposures and tolerance to innocuous antigens are required to maintain tissue homeostasis and integrity. Conversely, dysregulated innate immune responses manifest as sustained and self-perpetuating tissue damage rather than controlled tissue repair. In this article we review aspects of Toll-like receptor function that are relevant to the development of acute lung injury and chronic obstructive lung diseases as well as resistance to frequently associated microbial infections.",2010 Nov 25,"['Lafferty, Erin I', 'Qureshi, Salman T', 'Schnare, Markus']",J Inflamm (Lond),,,True
e8c2bc95762a2aefd919b02ae90131bc67716140,PMC,Liposome-Coupled Antigens Are Internalized by Antigen-Presenting Cells via Pinocytosis and Cross-Presented to CD8(+) T Cells,http://dx.doi.org/10.1371/journal.pone.0015225,PMC3003686,21179411,CC BY,"We have previously demonstrated that antigens chemically coupled to the surface of liposomes consisting of unsaturated fatty acids were cross-presented by antigen-presenting cells (APCs) to CD8(+) T cells, and that this process resulted in the induction of antigen-specific cytotoxic T lymphocytes. In the present study, the mechanism by which the liposome-coupled antigens were cross-presented to CD8(+) T cells by APCs was investigated. Confocal laser scanning microscopic analysis demonstrated that antigens coupled to the surface of unsaturated-fatty-acid-based liposomes received processing at both MHC class I and class II compartments, while most of the antigens coupled to the surface of saturated-fatty-acid-based liposomes received processing at the class II compartment. In addition, flow cytometric analysis demonstrated that antigens coupled to the surface of unsaturated-fatty-acid-liposomes were taken up by APCs even in a 4°C environment; this was not true of saturated-fatty-acid-liposomes. When two kinds of inhibitors, dimethylamiloride (DMA) and cytochalasin B, which inhibit pinocytosis and phagocytosis by APCs, respectively, were added to the culture of APCs prior to the antigen pulse, DMA but not cytochalasin B significantly reduced uptake of liposome-coupled antigens. Further analysis of intracellular trafficking of liposomal antigens using confocal laser scanning microscopy revealed that a portion of liposome-coupled antigens taken up by APCs were delivered to the lysosome compartment. In agreement with the reduction of antigen uptake by APCs, antigen presentation by APCs was significantly inhibited by DMA, and resulted in the reduction of IFN-γ production by antigen-specific CD8(+) T cells. These results suggest that antigens coupled to the surface of liposomes consisting of unsaturated fatty acids might be pinocytosed by APCs, loaded onto the class I MHC processing pathway, and presented to CD8(+) T cells. Thus, these liposome-coupled antigens are expected to be applicable for the development of vaccines that induce cellular immunity.",2010 Dec 17,"['Tanaka, Yuriko', 'Taneichi, Maiko', 'Kasai, Michiyuki', 'Kakiuchi, Terutaka', 'Uchida, Tetsuya']",PLoS One,,,True
d3f7afa8b4d0f21b23ccb1135dec12356375f5cc,PMC,Therapeutic Vaccination in Chronic Hepatitis B: Preclinical Studies in the Woodchuck,http://dx.doi.org/10.1155/2010/817580,PMC3003998,21188201,CC BY,"Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to a satisfactory result. Induction of HBV-specific T cells by therapeutic vaccination or immunotherapies may be an innovative strategy to overcome virus persistence. Vaccination with commercially available HBV vaccines in patients did not result in effective control of HBV infection, suggesting that new formulations of therapeutic vaccines are needed. The woodchuck (Marmota monax) is a useful preclinical model for developing the new therapeutic approaches in chronic hepadnaviral infections. Several innovative approaches combining antiviral treatments with nucleos(t)ide analogues, DNA vaccines, and protein vaccines were tested in the woodchuck model. In this paper we summarize the available data concerning therapeutic immunization and gene therapy using recombinant viral vectors approaches in woodchucks, which show encouraging results. In addition, we present potential innovations in immunomodulatory strategies to be evaluated in this animal model.",2010 Sep 7,"['Kosinska, Anna D.', 'Zhang, Ejuan', 'Lu, Mengji', 'Roggendorf, Michael']",Hepat Res Treat,,,True
4bf4126bc494f791347e285c91b25bc2814beb4d,PMC,The Dual Role of TNF in Pulmonary Edema,http://dx.doi.org/10.4103/0975-3583.59983,PMC3004168,21188088,CC BY,"—Pulmonary edema, a major manifestation of left ventricular heart failure, renal insufficiency, shock, diffuse alveolar damage and lung hypersensitivity states, is a significant medical problem worldwide and can be life-threatening. The proinflammatory cytokine tumor necrosis factor (TNF) has been shown to contribute to the pathogenesis and development of pulmonary edema. However, some recent studies have demonstrated surprisingly that TNF can also promote alveolar fluid reabsorption in vivo and in vitro. This protective effect of the cytokine is mediated by the lectin-like domain of the cytokine, which is spatially distinct from the TNF receptor binding sites. The TIP peptide, a synthetic mimic of the lectin-like domain of TNF, can significantly increase alveolar fluid clearance and improve lung compliance in pulmonary edema models. In this review, we will discuss the dual role of TNF in pulmonary edema. ABBREVIATIONS: —tumor necrosis factor (TNF); acute lung injury (ALI); acute respiratory distress syndrome (ARDS); positive end-expiratory pressure (PEEP);epithelial sodium channel (ENaC);neural precursor cell-expressed developmentally downregulated (gene 4) protein (Nedd4-2);serum and glucocorticoid dependent kinase (Sgk-1);insulin-like growth factor 1 (IGF-1);Protein Kinase C (PKC);reactive oxygen species (ROS);myosin light chain (MLC);pneumolysin (PLY);listeriolysin (LLO);interleukin (IL);bronchoalveolar lavage fluids (BALF);Bacillus Calmette-Guerin (BCG);TNF receptor type 1 (TNFR1); TNF receptor type 2 (TNF-R2);",2010 Jan-Mar,"['Yang, Guang', 'Hamacher, Jürg', 'Gorshkov, Boris', 'White, Richard', 'Sridhar, Supriya', 'Verin, Alexander', 'Chakraborty, Trinad', 'Lucas, Rudolf']",J Cardiovasc Dis Res,,,True
91e807f991ce190a25835b2cb4d0ee92ec63545d,PMC,Reconstructed Ancestral Sequences Improve Pathogen Identification Using Resequencing DNA Microarrays,http://dx.doi.org/10.1371/journal.pone.0015243,PMC3004854,21187950,CC BY,"We describe the benefit of using reconstructed ancestral sequences (RAS) on resequencing microarrays for rapid pathogen identification, with Enterobacteriaceae rpoB sequences as a model. Our results demonstrate a sharp improvement of call rate and accuracy when using RASs as compared to extant sequences. This improvement was attributed to the lower sequence divergence of RASs, which also expanded the sequence space covered by the microarray. Extension of this novel microarray design strategy to viruses, antimicrobial resistance elements or toxins is straightforward.",2010 Dec 20,"['Berthet, Nicolas', 'Deletoile, Alexis', 'Passet, Virginie', 'Kennedy, Giulia C.', 'Manuguerra, Jean-Claude', 'Cole, Stewart T.', 'Brisse, Sylvain']",PLoS One,,,True
9adcc3de8f703fe97f002f97da996f4924d5f5ba,PMC,Response to the challenges of pandemic H1N1 in a small island state: the Barbadian experience,http://dx.doi.org/10.1186/1471-2458-10-S1-S10,PMC3005570,21143820,CC BY,"BACKGROUND: Having been overwhelmed by the complexity of the response needed for the severe acute respiratory syndrome (SARS) epidemic, public health professionals in the small island state of Barbados put various measures in place to improve its response in the event of a pandemic METHODS: Data for this study was collected using Barbados’ National Influenza Surveillance System, which was revitalized in 2007. It is comprised of ten sentinel sites which send weekly notifications of acute respiratory illness (ARI) and severe acute respiratory illness (SARI) to the Office of the National Epidemiologist. During the 2009 H1N1 pandemic, meetings of the National Pandemic Planning Committee and the Technical Command Committee were convened. The pharmaceutical and non-pharmaceutical interventions (NPIs) implemented as a result of these meetings form the basis of the results presented in this paper. RESULTS: On June 3, 2009, Barbados reported its first case of 2009 H1N1. From June until October 2009, there were 155 laboratory confirmed cases of 2009 H1N1, with one additional case occurring in January 2010. For the outbreak period (June-October 2009), the surveillance team received reports of 2,483 ARI cases, compared to 412 cases for the same period in 2008. The total hospitalization rate due to SARIs for the year 2009 was 90.1 per 100,000 people, as compared to 7.3 per 100,000 people for 2008. Barbados’ pandemic response was characterized by a strong surveillance system combining active and passive surveillance, good risk communication strategy, a strengthened public and private sector partnership, and effective regional and international collaborations. Community restriction strategies such as school and workplace closures and cancellation of group events were not utilized as public health measures to delay the spread of the virus. Some health care facilities struggled with providing adequate isolation facilities. CONCLUSIONS: The number of confirmed cases was small but the significant surge in ARI and SARI cases indicate that the impact of the virus on the island was moderate. As a result of 2009 H1N1, virological surveillance has improved significantly and local, regional and international partnerships have been strengthened.",2010 Dec 3,"['Sobers-Grannum, Natasha', 'Springer, Karen', 'Ferdinand, Elizabeth', 'John, Joy St']",BMC Public Health,,,True
95e5e02c5d10df5d4559adba6bdf7a834b4d5329,PMC,Global health security and the International Health Regulations,http://dx.doi.org/10.1186/1471-2458-10-S1-S2,PMC3005574,21143824,CC BY,"Global nuclear proliferation, bioterrorism, and emerging infections have challenged national capacities to achieve and maintain global security. Over the last century, emerging infectious disease threats resulted in the development of the preliminary versions of the International Health Regulations (IHR) of the World Health Organization (WHO). The current HR(2005) contain major differences compared to earlier versions, including: substantial shifts from containment at the border to containment at the source of the event; shifts from a rather small disease list (smallpox, plague, cholera, and yellow fever) required to be reported, to all public health threats; and shifts from preset measures to tailored responses with more flexibility to deal with the local situations on the ground. The new IHR(2005) call for accountability. They also call for strengthened national capacity for surveillance and control; prevention, alert, and response to international public health emergencies beyond the traditional short list of required reporting; global partnership and collaboration; and human rights, obligations, accountability, and procedures of monitoring. Under these evolved regulations, as well as other measures, such as the Revolving Fund for vaccine procurement of the Pan American Health Organization (PAHO), global health security could be maintained in the response to urban yellow fever in Paraguay in 2008 and the influenza (H1N1) pandemic of 2009-2010.",2010 Dec 3,"['Andrus, Jon Kim', 'Aguilera, Ximena', 'Oliva, Otavio', 'Aldighieri, Sylvain']",BMC Public Health,,,True
9df9c07c5571ea37b99d01b8ecbfcac5625fa1ef,PMC,Laboratory capacity building for the International Health Regulations (IHR[2005]) in resource-poor countries: the experience of the African Field Epidemiology Network (AFENET),http://dx.doi.org/10.1186/1471-2458-10-S1-S8,PMC3005580,21143830,CC BY,"Laboratory is one of the core capacities that countries must develop for the implementation of the International Health Regulations (IHR[2005]) since laboratory services play a major role in all the key processes of detection, assessment, response, notification, and monitoring of events. While developed countries easily adapt their well-organized routine laboratory services, resource-limited countries need considerable capacity building as many gaps still exist. In this paper, we discuss some of the efforts made by the African Field Epidemiology Network (AFENET) in supporting laboratory capacity development in the Africa region. The efforts range from promoting graduate level training programs to building advanced technical, managerial and leadership skills to in-service short course training for peripheral laboratory staff. A number of specific projects focus on external quality assurance, basic laboratory information systems, strengthening laboratory management towards accreditation, equipment calibration, harmonization of training materials, networking and provision of pre-packaged laboratory kits to support outbreak investigation. Available evidence indicates a positive effect of these efforts on laboratory capacity in the region. However, many opportunities exist, especially to support the roll-out of these projects as well as attending to some additional critical areas such as biosafety and biosecuity. We conclude that AFENET’s approach of strengthening national and sub-national systems provide a model that could be adopted in resource-limited settings such as sub-Saharan Africa.",2010 Dec 3,"['Masanza, Monica Musenero', 'Nqobile, Ndlovu', 'Mukanga, David', 'Gitta, Sheba Nakacubo']",BMC Public Health,,,True
cb0ba244ebf7524d9303edd3c52946f08560f597,PMC,"Assessment of core capacities for the International Health Regulations (IHR[2005]) – Uganda, 2009",http://dx.doi.org/10.1186/1471-2458-10-S1-S9,PMC3005581,21143831,CC BY,"BACKGROUND: Uganda is currently implementing the International Health Regulations (IHR[2005]) within the context of Integrated Disease Surveillance and Response (IDSR). The IHR(2005) require countries to assess the ability of their national structures, capacities, and resources to meet the minimum requirements for surveillance and response. This report describes the results of the assessment undertaken in Uganda. METHODS: We conducted a descriptive cross-sectional assessment using the protocol developed by the World Health Organisation (WHO). The data collection tools were adapted locally and administered to a convenience sample of HR(2005) stakeholders, and frequency analyses were performed. RESULTS: Ugandan national laws relevant to the IHR(2005) existed, but they did not adequately support the full implementation of the IHR(2005). Correspondingly, there was a designated IHR National Focal Point (NFP), but surveillance activities and operational communications were limited to the health sector. All the districts (13/13) had designated disease surveillance offices, most had IDSR technical guidelines (92%, or 12/13), and all (13/13) had case definitions for infectious and zoonotic diseases surveillance. Surveillance guidelines were available at 57% (35/61) of the health facilities, while case definitions were available at 66% (40/61) of the health facilities. The priority diseases list, surveillance guidelines, case definitions and reporting tools were based on the IDSR strategy and hence lacked information on the IHR(2005). The rapid response teams at national and district levels lacked food safety, chemical and radio-nuclear experts. Similarly, there were no guidelines on the outbreak response to food, chemical and radio-nuclear hazards. Comprehensive preparedness plans incorporating IHR(2005) were lacking at national and district levels. A national laboratory policy existed and the strategic plan was being drafted. However, there were critical gaps hampering the efficient functioning of the national laboratory network. Finally, the points of entry for IHR(2005) implementation had not been designated. CONCLUSIONS: The assessment highlighted critical gaps to guide the IHR(2005) planning process. The IHR(2005) action plan should therefore be developed to foster national and international public health security.",2010 Dec 3,"['Wamala, Joseph F', 'Okot, Charles', 'Makumbi, Issa', 'Natseri, Nasan', 'Kisakye, Annet', 'Nanyunja, Miriam', 'Bakamutumaho, Barnabas', 'Lutwama, Julius J', 'Sreedharan, Rajesh', 'Xing, Jun', 'Gaturuku, Peter', 'Aisu, Thomas', 'Da Silveira, Fernando', 'Chungong, Stella']",BMC Public Health,,,True
9b2cf86c30314f63a3aeafcf615dc9a5dee997df,PMC,"Human immunome, bioinformatic analyses using HLA supermotifs and the parasite genome, binding assays, studies of human T cell responses, and immunization of HLA-A*1101 transgenic mice including novel adjuvants provide a foundation for HLA-A03 restricted CD8(+)T cell epitope based, adjuvanted vaccine protective against Toxoplasma gondii",http://dx.doi.org/10.1186/1745-7580-6-12,PMC3009956,21129215,CC BY,"BACKGROUND: Toxoplasmosis causes loss of life, cognitive and motor function, and sight. A vaccine is greatly needed to prevent this disease. The purpose of this study was to use an immmunosense approach to develop a foundation for development of vaccines to protect humans with the HLA-A03 supertype. Three peptides had been identified with high binding scores for HLA-A03 supertypes using bioinformatic algorhythms, high measured binding affinity for HLA-A03 supertype molecules, and ability to elicit IFN-γ production by human HLA-A03 supertype peripheral blood CD8(+ )T cells from seropositive but not seronegative persons. RESULTS: Herein, when these peptides were administered with the universal CD4(+)T cell epitope PADRE (AKFVAAWTLKAAA) and formulated as lipopeptides, or administered with GLA-SE either alone, or with Pam(2)Cys added, we found we successfully created preparations that induced IFN-γ and reduced parasite burden in HLA-A*1101(an HLA-A03 supertype allele) transgenic mice. GLA-SE is a novel emulsified synthetic TLR4 ligand that is known to facilitate development of T Helper 1 cell (TH1) responses. Then, so our peptides would include those expressed in tachyzoites, bradyzoites and sporozoites from both Type I and II parasites, we used our approaches which had identified the initial peptides. We identified additional peptides using bioinformatics, binding affinity assays, and study of responses of HLA-A03 human cells. Lastly, we found that immunization of HLA-A*1101 transgenic mice with all the pooled peptides administered with PADRE, GLA-SE, and Pam(2)Cys is an effective way to elicit IFN-γ producing CD8(+ )splenic T cells and protection. Immunizations included the following peptides together: KSFKDILPK (SAG1(224-232)); AMLTAFFLR (GRA6(164-172)); RSFKDLLKK (GRA7(134-142)); STFWPCLLR (SAG2C(13-21)); SSAYVFSVK((SPA250-258)); and AVVSLLRLLK(SPA(89-98)). This immunization elicited robust protection, measured as reduced parasite burden using a luciferase transfected parasite, luciferin, this novel, HLA transgenic mouse model, and imaging with a Xenogen camera. CONCLUSIONS: Toxoplasma gondii peptides elicit HLA-A03 restricted, IFN-γ producing, CD8(+ )T cells in humans and mice. These peptides administered with adjuvants reduce parasite burden in HLA-A*1101 transgenic mice. This work provides a foundation for immunosense based vaccines. It also defines novel adjuvants for newly identified peptides for vaccines to prevent toxoplasmosis in those with HLA-A03 supertype alleles.",2010 Dec 3,"['Cong, Hua', 'Mui, Ernest J', 'Witola, William H', 'Sidney, John', 'Alexander, Jeff', 'Sette, Alessandro', 'Maewal, Ajesh', 'McLeod, Rima']",Immunome Res,,,True
ac8f8e404ca0e3a052340bf089d90474b38d2b2b,PMC,DC-SIGN (CD209) Promoter −336 A/G Polymorphism Is Associated with Dengue Hemorrhagic Fever and Correlated to DC-SIGN Expression and Immune Augmentation,http://dx.doi.org/10.1371/journal.pntd.0000934,PMC3014977,21245921,CC BY,"BACKGROUND: The C-type lectin DC-SIGN (CD209) is known to be the major dengue receptor on human dendritic cells, and a single nucleotide polymorphism (SNP) in the promoter region of CD209 (−336 A/G; rs4804803) is susceptible to many infectious diseases. We reason that variations in the DC-SIGN gene might have a broad influence on viral replication and host immune responses. METHODS AND FINDINGS: We studied whether the rs4804803 SNP was associated with a susceptibility to dengue fever (DF) and/or dengue hemorrhagic fever (DHF) through genotyping analysis in a Taiwanese cohort. We generated monocyte-derived dendritic cells (MDDCs) from individuals with AA or AG genotype of rs4804803 to study the viral replication and immune responses for functional validation. A total of 574 DNA samples were genotyped, including 176 DF, 135 DHF, 143 other non-dengue febrile illnesses (OFI) and 120 population controls. A strong association between GG/AG genotypes of rs4804803 and risk of DHF was found when compared among DF, OFI and controls (p = 0.004, 3×10(−5) and 0.001, respectively). The AA genotype was associated with protection against dengue infection compared with OFI and controls (p = 0.002 and 0.020, respectively). Moreover, MDDCs from individuals with AG genotype with a higher cell surface DC-SIGN expression had a significantly higher TNFα, IL-12p40, and IP-10 production than those with AA genotype in response to dengue infection. However, the viral replication in MDDCs with AG genotype was significantly lower than those with AA genotype. With both genotypes, MDDCs revealed an increase in viral replication following the addition of anti-IP-10 neutralizing antibody. CONCLUSIONS/SIGNIFICANCE: The rs4804803 SNP in the CD209 promoter contributed to susceptibility to dengue infection and complication of DHF. This SNP with AG genotype affects the cell surface DC-SIGN expression related to immune augmentation and less viral replication.",2011 Jan 4,"['Wang, Lin', 'Chen, Rong-Fu', 'Liu, Jien-Wei', 'Lee, Ing-Kit', 'Lee, Chiu-Ping', 'Kuo, Ho-Chang', 'Huang, Shau-Ku', 'Yang, Kuender D.']",PLoS Negl Trop Dis,,,True
b936109e0b0de2cb59b2ed271614bb710e8e04af,PMC,Thermal Image Scanning for Influenza Border Screening: Results of an Airport Screening Study,http://dx.doi.org/10.1371/journal.pone.0014490,PMC3016318,21245928,CC BY,"BACKGROUND: Infrared thermal image scanners (ITIS) appear an attractive option for the mass screening of travellers for influenza, but there are no published data on their performance in airports. METHODS: ITIS was used to measure cutaneous temperature in 1275 airline travellers who had agreed to tympanic temperature measurement and respiratory sampling. The prediction by ITIS of tympanic temperature (37.8°C and 37.5°C) and of influenza infection was assessed using Receiver Operating Characteristic (ROC) curves and estimated sensitivity, specificity and positive predictive value (PPV). FINDINGS: Using front of face ITIS for prediction of tympanic temperature ≥37.8°C, the area under the ROC curve was 0.86 (95%CI 0.75–0.97) and setting sensitivity at 86% gave specificity of 71%. The PPV in this population of travellers, of whom 0.5% were febrile using this definition, was 1.5%. We identified influenza virus infection in 30 travellers (3 Type A and 27 Type B). For ITIS prediction of influenza infection the area under the ROC curve was 0.66 (0.56–0.75), a sensitivity of 87% gave specificity of 39%, and PPV of 2.8%. None of the 30 influenza-positive travellers had tympanic temperature ≥37.8°C at screening (95%CI 0% to 12%); three had no influenza symptoms. CONCLUSION: ITIS performed moderately well in detecting fever but in this study, during a seasonal epidemic of predominantly influenza type B, the proportion of influenza-infected travellers who were febrile was low and ITIS were not much better than chance at identifying travellers likely to be influenza-infected. Although febrile illness is more common in influenza A infections than influenza B infections, many influenza A infections are afebrile. Our findings therefore suggest that ITIS is unlikely to be effective for entry screening of travellers to detect influenza infection with the intention of preventing entry of the virus into a country.",2011 Jan 5,"['Priest, Patricia C.', 'Duncan, Alasdair R.', 'Jennings, Lance C.', 'Baker, Michael G.']",PLoS One,,,True
39eadd11ec6d5021711bcfa21f0cb6e183242c71,PMC,"Distinct Patterns of IFITM-Mediated Restriction of Filoviruses, SARS Coronavirus, and Influenza A Virus",http://dx.doi.org/10.1371/journal.ppat.1001258,PMC3017121,21253575,CC0,"Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV) hemagglutinin (HA) protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP(1,2)) of Marburg and Ebola filoviruses (MARV, EBOV). Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV) and entry mediated by the SARS-CoV spike (S) protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression.",2011 Jan 6,"['Huang, I-Chueh', 'Bailey, Charles C.', 'Weyer, Jessica L.', 'Radoshitzky, Sheli R.', 'Becker, Michelle M.', 'Chiang, Jessica J.', 'Brass, Abraham L.', 'Ahmed, Asim A.', 'Chi, Xiaoli', 'Dong, Lian', 'Longobardi, Lindsay E.', 'Boltz, Dutch', 'Kuhn, Jens H.', 'Elledge, Stephen J.', 'Bavari, Sina', 'Denison, Mark R.', 'Choe, Hyeryun', 'Farzan, Michael']",PLoS Pathog,,,True
96b070fe442137ec80f7736790ad13105c549dfd,PMC,A microbial detection array (MDA) for viral and bacterial detection,http://dx.doi.org/10.1186/1471-2164-11-668,PMC3017867,21108826,CC BY,"BACKGROUND: Identifying the bacteria and viruses present in a complex sample is useful in disease diagnostics, product safety, environmental characterization, and research. Array-based methods have proven utility to detect in a single assay at a reasonable cost any microbe from the thousands that have been sequenced. METHODS: We designed a pan-Microbial Detection Array (MDA) to detect all known viruses (including phages), bacteria and plasmids and developed a novel statistical analysis method to identify mixtures of organisms from complex samples hybridized to the array. The array has broader coverage of bacterial and viral targets and is based on more recent sequence data and more probes per target than other microbial detection/discovery arrays in the literature. Family-specific probes were selected for all sequenced viral and bacterial complete genomes, segments, and plasmids. Probes were designed to tolerate some sequence variation to enable detection of divergent species with homology to sequenced organisms, and to have no significant matches to the human genome sequence. RESULTS: In blinded testing on spiked samples with single or multiple viruses, the MDA was able to correctly identify species or strains. In clinical fecal, serum, and respiratory samples, the MDA was able to detect and characterize multiple viruses, phage, and bacteria in a sample to the family and species level, as confirmed by PCR. CONCLUSIONS: The MDA can be used to identify the suite of viruses and bacteria present in complex samples.",2010 Nov 25,"['Gardner, Shea N', 'Jaing, Crystal J', 'McLoughlin, Kevin S', 'Slezak, Tom R']",BMC Genomics,,,True
2032190765972c590630a370d6d2f088270ee9db,PMC,Proteins with RNA Chaperone Activity: A World of Diverse Proteins with a Common Task—Impediment of RNA Misfolding,http://dx.doi.org/10.1155/2011/532908,PMC3017892,21234377,CC BY,"Proteins with RNA chaperone activity are ubiquitous proteins that play important roles in cellular mechanisms. They prevent RNA from misfolding by loosening misfolded structures without ATP consumption. RNA chaperone activity is studied in vitro and in vivo using oligonucleotide- or ribozyme-based assays. Due to their functional as well as structural diversity, a common chaperoning mechanism or universal motif has not yet been identified. A growing database of proteins with RNA chaperone activity has been established based on evaluation of chaperone activity via the described assays. Although the exact mechanism is not yet understood, it is more and more believed that disordered regions within proteins play an important role. This possible mechanism and which proteins were found to possess RNA chaperone activity are discussed here.",2011 Dec 26,"Semrad, Katharina",Biochem Res Int,,,True
e9b30d08d16832b101208cf26d563cfefd8649bb,PMC,Assortativity and the Probability of Epidemic Extinction: A Case Study of Pandemic Influenza A (H1N1-2009),http://dx.doi.org/10.1155/2011/194507,PMC3017939,21234337,CC BY,"Unlike local transmission of pandemic influenza A (H1N1-2009), which was frequently driven by school children, most cases identified in long-distance intranational and international travelers have been adults. The present study examines the relationship between the probability of temporary extinction and the age-dependent next-generation matrix, focusing on the impact of assortativity. Preferred mixing captures as a good approximation the assortativity of a heterogeneously mixing population. We show that the contribution of a nonmaintenance host (i.e., a host type which cannot sustain transmission on its own) to the risk of a major epidemic is greatly diminished as mixing patterns become more assortative, and in such a scenario, a higher proportion of non-maintenance hosts among index cases elevates the probability of extinction. Despite the presence of various other epidemiological factors that undoubtedly influenced the delay between first importations and the subsequent epidemic, these results suggest that the dominance of adults among imported cases represents one of the possible factors explaining the delays in geographic spread observed during the recent pandemic.",2011 Dec 23,"['Nishiura, Hiroshi', 'Cook, Alex R.', 'Cowling, Benjamin J.']",Interdiscip Perspect Infect Dis,,,True
d6631a0f06bb98c73bfde3c98faf886c8be05522,PMC,"Reporting errors in infectious disease outbreaks, with an application to Pandemic Influenza A/H1N1",http://dx.doi.org/10.1186/1742-5573-7-12,PMC3018365,21159178,CC BY,"BACKGROUND: Effectively responding to infectious disease outbreaks requires a well-informed response. Quantitative methods for analyzing outbreak data and estimating key parameters to characterize the spread of the outbreak, including the reproductive number and the serial interval, often assume that the data collected is complete. In reality reporting delays, undetected cases or lack of sensitive and specific tests to diagnose disease lead to reporting errors in the case counts. Here we provide insight on the impact that such reporting errors might have on the estimation of these key parameters. RESULTS: We show that when the proportion of cases reported is changing through the study period, the estimates of key epidemiological parameters are biased. Using data from the Influenza A/H1N1 outbreak in La Gloria, Mexico, we provide estimates of these parameters, accounting for possible reporting errors, and show that they can be biased by as much as 33%, if reporting issues are not accounted for. CONCLUSIONS: Failure to account for missing data can lead to misleading and inaccurate estimates of epidemic parameters.",2010 Dec 15,"['White, Laura F', 'Pagano, Marcello']",Epidemiol Perspect Innov,,,True
50ed67f9700cce235cfb173d78b22053243c1d38,PMC,Alzheimer's Disease: A Pathogenetic Autoimmune Disorder Caused by Herpes Simplex in a Gene-Dependent Manner,http://dx.doi.org/10.4061/2010/140539,PMC3018626,21234306,CC BY,"Herpes simplex is implicated in Alzheimer's disease and viral infection produces Alzheimer's disease like pathology in mice. The virus expresses proteins containing short contiguous amino acid stretches (5–9aa “vatches” = viralmatches) homologous to APOE4, clusterin, PICALM, and complement receptor 1, and to over 100 other gene products relevant to Alzheimer's disease, which are also homologous to proteins expressed by other pathogens implicated in Alzheimer's disease. Such homology, reiterated at the DNA level, suggests that gene association studies have been tracking infection, as well as identifying key genes, demonstrating a role for pathogens as causative agents. Vatches may interfere with the function of their human counterparts, acting as dummy ligands, decoy receptors, or via interactome interference. They are often immunogenic, and antibodies generated in response to infection may target their human counterparts, producing protein knockdown, or generating autoimmune responses that may kill the neurones in which the human homologue resides, a scenario supported by immune activation in Alzheimer's disease. These data may classify Alzheimer's disease as an autoimmune disorder created by pathogen mimicry of key Alzheimer's disease-related proteins. It may well be prevented by vaccination and regular pathogen detection and elimination, and perhaps stemmed by immunosuppression or antibody adsorption-related therapies.",2010 Dec 29,"Carter, C. J.",Int J Alzheimers Dis,,,True
0c4cea0b243a4aa5920a4861426a3c6bb250cf3c,PMC,"SISEA activities in Pasteur Institute in Nha Trang, Vietnam, during 2008–2009",,PMC3019433,,CC BY,,2011 Jan 10,"['Chien, Bui Trong', 'Mai, Vien Quang', 'Mai, Trinh Thi Xuan', 'Nam, Nguyen Hai', 'Thuy, Ðoan Thi thanh']",BMC Proc,,,False
17a82f57ae67bf99733f4bc5ffa157c9176c85fd,PMC,Epidemiology and viral etiologies of Severe Acute Respiratory Infections (SARI) in the Northern Vietnam,,PMC3019434,,CC BY,,2011 Jan 10,"['Hien, Nguyen Tran', 'Thi Thuong, Nguyen', 'Thiem, Vu Dinh', 'Minh, Nguyen Quang', 'Duong, Tran Nhu']",BMC Proc,,,False
c7e06bcb6281367d876863d5a26813e2ad337301,PMC,Identification of viruses in Acute Lower Respiratory Infections (ALRI) in Lao People's Democratic Republic,,PMC3019503,,CC BY,,2011 Jan 10,"['Sentilhes, Anne-Charlotte', 'Xaysitthideth, Vimatha', 'Rith, Sareth', 'Ongkhamme, Somvay', 'Sisouk, Thongchanh', 'Phonekeo, Darouny', 'Bernatas, Jean-Jacques', 'Deubel, Vincent', 'Buchy, Philippe', 'Brey, Paul', 'Vongphrachanh, Phengta']",BMC Proc,,,False
385c5add434a1ed8a8868fe0c37e63486387b454,PMC,The SARS coronavirus E protein interacts with the PALS1 and alters tight junction formation and epithelial morphogenesis,,PMC3019508,,CC BY,,2011 Jan 10,"['Teoh, Kim-Tat', 'Siu, Yu-Lam', 'Chan, Wing-Lim', 'Schlüter, Marc A', 'Liu, Chia-Jen', 'Malik Peiris, J S', 'Bruzzone, Roberto', 'Margolis, Benjamin', 'Nal, Béatrice']",BMC Proc,,,False
0aef63f4f4c4cb195e71b50d0c6e721aba9f2a81,PMC,Investigation of Antibody-Dependent Enhancement (ADE) of SARS coronavirus infection and its role in pathogenesis of SARS,,PMC3019510,,CC BY,,2011 Jan 10,"['Yip, Ming S', 'Cheung, Chung Y', 'Li, Ping H', 'Bruzzone, Roberto', 'Peiris, JS Malik', 'Jaume, Martial']",BMC Proc,,,True
4b2a69ec1289a04f3a94db719f855631f93f2d54,PMC,Liposome-Coupled Peptides Induce Long-Lived Memory CD8(+) T Cells Without CD4(+) T Cells,http://dx.doi.org/10.1371/journal.pone.0015091,PMC3020143,21264321,CC BY,"CD8(+) T cells provide broad immunity to viruses, because they are able to recognize all types of viral proteins. Therefore, the development of vaccines capable of inducing long-lived memory CD8(+) T cells is desired to prevent diseases, especially those for which no vaccines currently exist. However, in designing CD8(+) T cell vaccines, the role of CD4(+) T cells in the induction and maintenance of memory CD8(+) T cells remains uncertain. In the present study, the necessity or not of CD4(+) T cells in the induction and maintenance of memory CD8(+) T cells was investigated in mice immunized with liposome-coupled CTL epitope peptides. When OVA-derived CTL epitope peptides were chemically coupled to the surfaces of liposomes and inoculated into mice, both primary and secondary CTL responses were successfully induced. The results were further confirmed in CD4(+) T cell-eliminated mice, suggesting that CD4(+) T cells were not required for the generation of memory CD8(+) T cells in the case of immunization with liposome-coupled peptides. Thus, surface-linked liposomal antigens, capable of inducing long-lived memory CD8(+) T cells without the contribution of CD4(+) T cells, might be applicable for the development of vaccines to prevent viral infection, especially for those viruses that evade humoral immunity by varying their surface proteins, such as influenza viruses, HIV, HCV, SARS coronaviruses, and Ebola viruses.",2010 Nov 30,"['Taneichi, Maiko', 'Tanaka, Yuriko', 'Kakiuchi, Terutaka', 'Uchida, Tetsuya']",PLoS One,,,True
80ea83eb20c374075380eadb6df930f2d356ea62,PMC,Engineered Toxins “Zymoxins” Are Activated by the HCV NS3 Protease by Removal of an Inhibitory Protein Domain,http://dx.doi.org/10.1371/journal.pone.0015916,PMC3021518,21264238,CC BY,"The synthesis of inactive enzyme precursors, also known as “zymogens,” serves as a mechanism for regulating the execution of selected catalytic activities in a desirable time and/or site. Zymogens are usually activated by proteolytic cleavage. Many viruses encode proteases that execute key proteolytic steps of the viral life cycle. Here, we describe a proof of concept for a therapeutic approach to fighting viral infections through eradication of virally infected cells exclusively, thus limiting virus production and spread. Using the hepatitis C virus (HCV) as a model, we designed two HCV NS3 protease-activated “zymogenized” chimeric toxins (which we denote “zymoxins”). In these recombinant constructs, the bacterial and plant toxins diphtheria toxin A (DTA) and Ricin A chain (RTA), respectively, were fused to rationally designed inhibitor peptides/domains via an HCV NS3 protease-cleavable linker. The above toxins were then fused to the binding and translocation domains of Pseudomonas exotoxin A in order to enable translocation into the mammalian cells cytoplasm. We show that these toxins exhibit NS3 cleavage dependent increase in enzymatic activity upon NS3 protease cleavage in vitro. Moreover, a higher level of cytotoxicity was observed when zymoxins were applied to NS3 expressing cells or to HCV infected cells, demonstrating a potential therapeutic window. The increase in toxin activity correlated with NS3 protease activity in the treated cells, thus the therapeutic window was larger in cells expressing recombinant NS3 than in HCV infected cells. This suggests that the “zymoxin” approach may be most appropriate for application to life-threatening acute infections where much higher levels of the activating protease would be expected.",2011 Jan 14,"['Shapira, Assaf', 'Gal-Tanamy, Meital', 'Nahary, Limor', 'Litvak-Greenfeld, Dana', 'Zemel, Romy', 'Tur-Kaspa, Ran', 'Benhar, Itai']",PLoS One,,,True
0700c01d64e50ef5ae5943328bd734718cf614f4,PMC,An Analysis on the Detection of Biological Contaminants Aboard Aircraft,http://dx.doi.org/10.1371/journal.pone.0014520,PMC3022008,21264266,CC BY,"The spread of infectious disease via commercial airliner travel is a significant and realistic threat. To shed some light on the feasibility of detecting airborne pathogens, a sensor integration study has been conducted and computational investigations of contaminant transport in an aircraft cabin have been performed. Our study took into consideration sensor sensitivity as well as the time-to-answer, size, weight and the power of best available commercial off-the-shelf (COTS) devices. We conducted computational fluid dynamics simulations to investigate three types of scenarios: (1) nominal breathing (up to 20 breaths per minute) and coughing (20 times per hour); (2) nominal breathing and sneezing (4 times per hour); and (3) nominal breathing only. Each scenario was implemented with one or seven infectious passengers expelling air and sneezes or coughs at the stated frequencies. Scenario 2 was implemented with two additional cases in which one infectious passenger expelled 20 and 50 sneezes per hour, respectively. All computations were based on 90 minutes of sampling using specifications from a COTS aerosol collector and biosensor. Only biosensors that could provide an answer in under 20 minutes without any manual preparation steps were included. The principal finding was that the steady-state bacteria concentrations in aircraft would be high enough to be detected in the case where seven infectious passengers are exhaling under scenarios 1 and 2 and where one infectious passenger is actively exhaling in scenario 2. Breathing alone failed to generate sufficient bacterial particles for detection, and none of the scenarios generated sufficient viral particles for detection to be feasible. These results suggest that more sensitive sensors than the COTS devices currently available and/or sampling of individual passengers would be needed for the detection of bacteria and viruses in aircraft.",2011 Jan 17,"['Hwang, Grace M.', 'DiCarlo, Anthony A.', 'Lin, Gene C.']",PLoS One,,,True
cddc369300f073cb0ba20e276fee32112502f4f7,PMC,Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses,http://dx.doi.org/10.1186/1471-2172-11-65,PMC3023737,21194475,CC BY,"BACKGROUND: Immunization with the spike protein (S) of severe acute respiratory syndrome (SARS)-coronavirus (CoV) in mice is known to produce neutralizing antibodies and to prevent the infection caused by SARS-CoV. Polyethylenimine 25K (PEI) is a cationic polymer which effectively delivers the plasmid DNA. RESULTS: In the present study, the immune responses of BALB/c mice immunized via intranasal (i.n.) route with SARS DNA vaccine (pci-S) in a PEI/pci-S complex form have been examined. The size of the PEI/pci-S nanoparticles appeared to be around 194.7 ± 99.3 nm, and the expression of the S mRNA and protein was confirmed in vitro. The mice immunized with i.n. PEI/pci-S nanoparticles produced significantly (P < 0.05) higher S-specific IgG1 in the sera and mucosal secretory IgA in the lung wash than those in mice treated with pci-S alone. Compared to those in mice challenged with pci-S alone, the number of B220(+ )cells found in PEI/pci-S vaccinated mice was elevated. Co-stimulatory molecules (CD80 and CD86) and class II major histocompatibility complex molecules (I-A(d)) were increased on CD11c(+ )dendritic cells in cervical lymph node from the mice after PEI/pci-S vaccination. The percentage of IFN-γ-, TNF-α- and IL-2-producing cells were higher in PEI/pci-S vaccinated mice than in control mice. CONCLUSION: These results showed that intranasal immunization with PEI/pci-S nanoparticles induce antigen specific humoral and cellular immune responses.",2010 Dec 31,"['Shim, Byoung-Shik', 'Park, Sung-Moo', 'Quan, Ji-Shan', 'Jere, Dhananjay', 'Chu, Hyuk', 'Song, Man Ki', 'Kim, Dong Wook', 'Jang, Yong-Suk', 'Yang, Moon-Sik', 'Han, Seung Hyun', 'Park, Yong-Ho', 'Cho, Chong-Su', 'Yun, Cheol-Heui']",BMC Immunol,,,True
f8abd9e10df6beeffec38bc7dd7083318e0d69ed,PMC,Improvement of different vaccine delivery systems for cancer therapy,http://dx.doi.org/10.1186/1476-4598-10-3,PMC3024302,21211062,CC BY,"Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs) have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs) such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP) have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.",2011 Jan 7,"['Bolhassani, Azam', 'Safaiyan, Shima', 'Rafati, Sima']",Mol Cancer,,,True
1763110ecc1742f6158f410a0c4f0b923118fd79,PMC,The Ras–PI3K Signaling Pathway Is Involved in Clathrin-Independent Endocytosis and the Internalization of Influenza Viruses,http://dx.doi.org/10.1371/journal.pone.0016324,PMC3024431,21283725,CC BY,"BACKGROUND: Influenza virus infection causes highly contagious, severe respiratory disorders and gives rise to thousands of deaths every year; however, the efficacy of currently approved defense strategies, including vaccines and neuraminidase inhibitors, is limited because the virus frequently acquires resistance via antigen drift and reassortment. It is therefore important to establish a novel, effective therapeutic strategy that is effective irrespective of viral subtype. METHODOLOGY/PRINCIPAL FINDINGS: Here, we identify the Ras–phosphoinositide 3-kinase (PI3K) signaling pathway as a host-cell regulatory mechanism for influenza virus entry. The binding of Ras to PI3K is specifically involved in clathrin-independent endocytosis, endosomal maturation, and intracellular transport of viruses, which result in decreased infectious efficacy of different subtypes of influenza viruses in cells lacking the Ras–PI3K interaction. Moreover, influenza virus infection indeed triggered Ras activation and subsequent PI3K activation in early endosomes. CONCLUSIONS/SIGNIFICANCE: Taken together, these results demonstrate that the Ras–PI3K signaling axis acts as a host-oriented mechanism for viral internalization. Given that virus incorporation is a process conserved among virus subtypes and species, this signaling pathway may provide a target for potent, well-tolerated prophylactics and therapeutics against a broad range of viruses.",2011 Jan 20,"['Fujioka, Yoichiro', 'Tsuda, Masumi', 'Hattori, Tomoe', 'Sasaki, Junko', 'Sasaki, Takehiko', 'Miyazaki, Tadaaki', 'Ohba, Yusuke']",PLoS One,,,True
464e498ad4c25f88b02533864c5415900e53e412,PMC,Full-length Ebola glycoprotein accumulates in the endoplasmic reticulum,http://dx.doi.org/10.1186/1743-422X-8-11,PMC3024955,21223600,CC BY,"The Filoviridae family comprises of Ebola and Marburg viruses, which are known to cause lethal hemorrhagic fever. However, there is no effective anti-viral therapy or licensed vaccines currently available for these human pathogens. The envelope glycoprotein (GP) of Ebola virus, which mediates entry into target cells, is cytotoxic and this effect maps to a highly glycosylated mucin-like region in the surface subunit of GP (GP1). However, the mechanism underlying this cytotoxic property of GP is unknown. To gain insight into the basis of this GP-induced cytotoxicity, HEK293T cells were transiently transfected with full-length and mucin-deleted (Δmucin) Ebola GP plasmids and GP localization was examined relative to the nucleus, endoplasmic reticulum (ER), Golgi, early and late endosomes using deconvolution fluorescent microscopy. Full-length Ebola GP was observed to accumulate in the ER. In contrast, GPΔmucin was uniformly expressed throughout the cell and did not localize in the ER. The Ebola major matrix protein VP40 was also co-expressed with GP to investigate its influence on GP localization. GP and VP40 co-expression did not alter GP localization to the ER. Also, when VP40 was co-expressed with the nucleoprotein (NP), it localized to the plasma membrane while NP accumulated in distinct cytoplasmic structures lined with vimentin. These latter structures are consistent with aggresomes and may serve as assembly sites for filoviral nucleocapsids. Collectively, these data suggest that full-length GP, but not GPΔmucin, accumulates in the ER in close proximity to the nuclear membrane, which may underscore its cytotoxic property.",2011 Jan 12,"['Bhattacharyya, Suchita', 'Hope, Thomas J']",Virol J,,,True
820f3633db1b3b98889e6a0d257d10d385be85c8,PMC,Prime immunization with rotavirus VLP 2/6 followed by boosting with an adenovirus expressing VP6 induces protective immunization against rotavirus in mice,http://dx.doi.org/10.1186/1743-422X-8-3,PMC3024956,21205330,CC BY,"BACKGROUND: Rotavirus (RV) is the main cause of severe gastroenteritis in children. An effective vaccination regime against RV can substantially reduce morbidity and mortality. Previous studies have demonstrated the efficacy of virus-like particles formed by RV VP2 and VP6 (VLP2/6), as well as that of recombinant adenovirus expressing RV VP6 (rAd), in eliciting protective immunities against RV. However, the efficacy of such prime-boost strategy, which incorporates VLP and rAd in inducing protective immunities against RV, has not been addressed. We assessed the immune effects of different regimens in mice, including rAd prime-VLP2/6 boost (rAd+VLP), VLP2/6 prime-rAd boost (VLP+rAd), rAd alone, and VLP alone. RESULTS: Mice immunized with the VLP+rAd regimen elicit stronger humoral, mucosal, and cellular immune responses than those immunized with other regimens. RV challenging experiments showed that the highest reduction (92.9%) in viral shedding was achieved in the VLP+rAd group when compared with rAd+VLP (25%), VLP alone (75%), or rAd alone (40%) treatment groups. The reduction in RV shedding in mice correlated with fecal IgG (r = 0.95773, P = 0.04227) and IgA (r = 0.96137, P = 0.038663). CONCLUSIONS: A VLP2/6 prime-rAd boost regimen is effective in conferring immunoprotection against RV challenge in mice. This finding may lay the groundwork for an alternative strategy in novel RV vaccine development.",2011 Jan 5,"['Zhou, Hongli', 'Guo, Li', 'Wang, Min', 'Qu, Jianguo', 'Zhao, Zhendong', 'Wang, Jianwei', 'Hung, Tao']",Virol J,,,True
7941d4720a1cb228b2380a42885532440f5b7a0a,PMC,A Sensitive Assay for Virus Discovery in Respiratory Clinical Samples,http://dx.doi.org/10.1371/journal.pone.0016118,PMC3025933,21283679,CC BY,"In 5–40% of respiratory infections in children, the diagnostics remain negative, suggesting that the patients might be infected with a yet unknown pathogen. Virus discovery cDNA-AFLP (VIDISCA) is a virus discovery method based on recognition of restriction enzyme cleavage sites, ligation of adaptors and subsequent amplification by PCR. However, direct discovery of unknown pathogens in nasopharyngeal swabs is difficult due to the high concentration of ribosomal RNA (rRNA) that acts as competitor. In the current study we optimized VIDISCA by adjusting the reverse transcription enzymes and decreasing rRNA amplification in the reverse transcription, using hexamer oligonucleotides that do not anneal to rRNA. Residual cDNA synthesis on rRNA templates was further reduced with oligonucleotides that anneal to rRNA but can not be extended due to 3′-dideoxy-C6-modification. With these modifications >90% reduction of rRNA amplification was established. Further improvement of the VIDISCA sensitivity was obtained by high throughput sequencing (VIDISCA-454). Eighteen nasopharyngeal swabs were analysed, all containing known respiratory viruses. We could identify the proper virus in the majority of samples tested (11/18). The median load in the VIDISCA-454 positive samples was 7.2 E5 viral genome copies/ml (ranging from 1.4 E3–7.7 E6). Our results show that optimization of VIDISCA and subsequent high-throughput-sequencing enhances sensitivity drastically and provides the opportunity to perform virus discovery directly in patient material.",2011 Jan 24,"['de Vries, Michel', 'Deijs, Martin', 'Canuti, Marta', 'van Schaik, Barbera D. C.', 'Faria, Nuno R.', 'van de Garde, Martijn D. B.', 'Jachimowski, Loes C. M.', 'Jebbink, Maarten F.', 'Jakobs, Marja', 'Luyf, Angela C. M.', 'Coenjaerts, Frank E. J.', 'Claas, Eric C. J.', 'Molenkamp, Richard', 'Koekkoek, Sylvie M.', 'Lammens, Christine', 'Leus, Frank', 'Goossens, Herman', 'Ieven, Margareta', 'Baas, Frank', 'van der Hoek, Lia']",PLoS One,,,True
8ba5919b2b4c229c9c1685852cf19a1d727ac220,PMC,Assessment of Virally Vectored Autoimmunity as a Biocontrol Strategy for Cane Toads,http://dx.doi.org/10.1371/journal.pone.0014576,PMC3026784,21283623,CC0,"BACKGROUND: The cane toad, Bufo (Chaunus) marinus, is one of the most notorious vertebrate pests introduced into Australia over the last 200 years and, so far, efforts to identify a naturally occurring B. marinus-specific pathogen for use as a biological control agent have been unsuccessful. We explored an alternative approach that entailed genetically modifying a pathogen with broad host specificity so that it no longer caused disease, but carried a gene to disrupt the cane toad life cycle in a species specific manner. METHODOLOGY/PRINCIPAL FINDINGS: The adult beta globin gene was selected as the model gene for proof of concept of autoimmunity as a biocontrol method for cane toads. A previous report showed injection of bullfrog tadpoles with adult beta globin resulted in an alteration in the form of beta globin expressed in metamorphs as well as reduced survival. In B. marinus we established for the first time that the switch from tadpole to adult globin exists. The effect of injecting B. marinus tadpoles with purified recombinant adult globin protein was then assessed using behavioural (swim speed in tadpoles and jump length in metamorphs), developmental (time to metamorphosis, weight and length at various developmental stages, protein profile of adult globin) and genetic (adult globin mRNA levels) measures. However, we were unable to detect any differences between treated and control animals. Further, globin delivery using Bohle iridovirus, an Australian ranavirus isolate belonging to the Iridovirus family, did not reduce the survival of metamorphs or alter the form of beta globin expressed in metamorphs. CONCLUSIONS/SIGNIFICANCE: While we were able to show for the first time that the switch from tadpole to adult globin does occur in B. marinus, we were not able to induce autoimmunity and disrupt metamorphosis. The short development time of B. marinus tadpoles may preclude this approach.",2011 Jan 25,"['Pallister, Jackie A.', 'Halliday, Damien C.T.', 'Robinson, Anthony J.', 'Venables, Daryl', 'Voysey, Rhonda D.', 'Boyle, Donna G.', 'Shanmuganathan, Thayalini', 'Hardy, Christopher M.', 'Siddon, Nicole A.', 'Hyatt, Alex D.']",PLoS One,,,True
bb89ed5e7ed332cbc8565262db8a04d55e2869ef,PMC,Mechanism of Inhibition of Enveloped Virus Membrane Fusion by the Antiviral Drug Arbidol,http://dx.doi.org/10.1371/journal.pone.0015874,PMC3026800,21283579,CC BY,"The broad-spectrum antiviral arbidol (Arb) inhibits cell entry of enveloped viruses by blocking viral fusion with host cell membrane. To better understand Arb mechanism of action, we investigated its interactions with phospholipids and membrane peptides. We demonstrate that Arb associates with phospholipids in the micromolar range. NMR reveals that Arb interacts with the polar head-group of phospholipid at the membrane interface. Fluorescence studies of interactions between Arb and either tryptophan derivatives or membrane peptides reconstituted into liposomes show that Arb interacts with tryptophan in the micromolar range. Interestingly, apparent binding affinities between lipids and tryptophan residues are comparable with those of Arb IC50 of the hepatitis C virus (HCV) membrane fusion. Since tryptophan residues of membrane proteins are known to bind preferentially at the membrane interface, these data suggest that Arb could increase the strength of virus glycoprotein's interactions with the membrane, due to a dual binding mode involving aromatic residues and phospholipids. The resulting complexation would inhibit the expected viral glycoprotein conformational changes required during the fusion process. Our findings pave the way towards the design of new drugs exhibiting Arb-like interfacial membrane binding properties to inhibit early steps of virus entry, i.e., attractive targets to combat viral infection.",2011 Jan 25,"['Teissier, Elodie', 'Zandomeneghi, Giorgia', 'Loquet, Antoine', 'Lavillette, Dimitri', 'Lavergne, Jean-Pierre', 'Montserret, Roland', 'Cosset, François-Loïc', 'Böckmann, Anja', 'Meier, Beat H.', 'Penin, François', 'Pécheur, Eve-Isabelle']",PLoS One,,,True
1546fd2f004f233eea33c99a54f863ee80ffedaf,PMC,Evaluation of an Adjustable Epidemiologic Information System,http://dx.doi.org/10.1371/journal.pone.0014596,PMC3029279,21298043,CC BY,"BACKGROUND: In order to facilitate public health response and to achieve early control of infectious disease epidemics, an adjustable epidemiologic information system (AEIS) was established in the Taiwan public health network in February 2006. METHODOLOGY/PRINCIPAL FINDINGS: The performance of AEIS for the period 2006 through 2008 was evaluated based on a number of response times (RT) and the public health impact. After implementation of the system, the apparent overall shortened RT was mainly due to the shortening of personnel response time (PRT) and the time needed to draft a new questionnaire that incurred as personnel-system interface (PSI); PRT dropped from a fluctuating range of 9.8 ∼28.8 days in the first four months to <10 days in the following months and remained low till 2008 (0.88±1.52 days). The PSIs for newly emerged infectious diseases were 2.6 and 3.4 person-hours for H5N1 in 2007 and chikungunya in 2008, respectively, a much improvement from 1142.5 person-hours for SARS in 2003. The duration of each rubella epidemic cluster was evaluated as public health impact and showed a shortening trend (p = 0.019) that concurred with the shortening of PRT from 64.8±47.3 to 25.2±38.2 hours per cluster (p<0.0001). CONCLUSIONS/SIGNIFICANCE: The first evaluation of the novel instrument AEIS that had been used to assist Taiwan's multi-level government for infectious diseases control demonstrated that it was well integrated into the existing public health infrastructure. It provided flexible tools and computer algorithms with friendly interface for timely data collection, integration, and analysis; as a result, it shortened RTs, filled in gaps of personnel lacking sufficient experiences, created a more efficient flow of response, and identified asymptomatic/mild cases early to minimize further spreading. With further development, AEIS is anticipated to be useful in the application of other acute public health events needing immediate orchestrated data collection and public health actions.",2011 Jan 27,"['Wu, Jiunn-Shyan Julian', 'Shih, Fu-Yuan', 'Chiu, Chan-Hsien', 'Yeh, Yuan-Lih', 'Yan, Jer-Jea', 'King, Chwan-Chuen', 'Ho, Mei-Shang']",PLoS One,,,True
c8eebd3a71f902afe3e21142b9ea8b4f7bf60018,PMC,Evaluation of an Adjustable Epidemiologic Information System,http://dx.doi.org/10.1371/journal.pone.0014596,PMC3029279,21298043,CC BY,"BACKGROUND: In order to facilitate public health response and to achieve early control of infectious disease epidemics, an adjustable epidemiologic information system (AEIS) was established in the Taiwan public health network in February 2006. METHODOLOGY/PRINCIPAL FINDINGS: The performance of AEIS for the period 2006 through 2008 was evaluated based on a number of response times (RT) and the public health impact. After implementation of the system, the apparent overall shortened RT was mainly due to the shortening of personnel response time (PRT) and the time needed to draft a new questionnaire that incurred as personnel-system interface (PSI); PRT dropped from a fluctuating range of 9.8 ∼28.8 days in the first four months to <10 days in the following months and remained low till 2008 (0.88±1.52 days). The PSIs for newly emerged infectious diseases were 2.6 and 3.4 person-hours for H5N1 in 2007 and chikungunya in 2008, respectively, a much improvement from 1142.5 person-hours for SARS in 2003. The duration of each rubella epidemic cluster was evaluated as public health impact and showed a shortening trend (p = 0.019) that concurred with the shortening of PRT from 64.8±47.3 to 25.2±38.2 hours per cluster (p<0.0001). CONCLUSIONS/SIGNIFICANCE: The first evaluation of the novel instrument AEIS that had been used to assist Taiwan's multi-level government for infectious diseases control demonstrated that it was well integrated into the existing public health infrastructure. It provided flexible tools and computer algorithms with friendly interface for timely data collection, integration, and analysis; as a result, it shortened RTs, filled in gaps of personnel lacking sufficient experiences, created a more efficient flow of response, and identified asymptomatic/mild cases early to minimize further spreading. With further development, AEIS is anticipated to be useful in the application of other acute public health events needing immediate orchestrated data collection and public health actions.",2011 Jan 27,"['Wu, Jiunn-Shyan Julian', 'Shih, Fu-Yuan', 'Chiu, Chan-Hsien', 'Yeh, Yuan-Lih', 'Yan, Jer-Jea', 'King, Chwan-Chuen', 'Ho, Mei-Shang']",PLoS One,,,False
61e9b0e59092872671011d724f22401d3c2f8288,PMC,A Recombinant Vaccine of H5N1 HA1 Fused with Foldon and Human IgG Fc Induced Complete Cross-Clade Protection against Divergent H5N1 Viruses,http://dx.doi.org/10.1371/journal.pone.0016555,PMC3029370,21304591,CC BY,"Development of effective vaccines to prevent influenza, particularly highly pathogenic avian influenza (HPAI) caused by influenza A virus (IAV) subtype H5N1, is a challenging goal. In this study, we designed and constructed two recombinant influenza vaccine candidates by fusing hemagglutinin 1 (HA1) fragment of A/Anhui/1/2005(H5N1) to either Fc of human IgG (HA1-Fc) or foldon plus Fc (HA1-Fdc), and evaluated their immune responses and cross-protection against divergent strains of H5N1 virus. Results showed that these two recombinant vaccines induced strong immune responses in the vaccinated mice, which specifically reacted with HA1 proteins and an inactivated heterologous H5N1 virus. Both proteins were able to cross-neutralize infections by one homologous strain (clade 2.3) and four heterologous strains belonging to clades 0, 1, and 2.2 of H5N1 pseudoviruses as well as three heterologous strains (clades 0, 1, and 2.3.4) of H5N1 live virus. Importantly, immunization with these two vaccine candidates, especially HA1-Fdc, provided complete cross-clade protection against high-dose lethal challenge of different strains of H5N1 virus covering clade 0, 1, and 2.3.4 in the tested mouse model. This study suggests that the recombinant fusion proteins, particularly HA1-Fdc, could be developed into an efficacious universal H5N1 influenza vaccine, providing cross-protection against infections by divergent strains of highly pathogenic H5N1 virus.",2011 Jan 27,"['Du, Lanying', 'Leung, Virtual Ho-Chuen', 'Zhang, Xiujuan', 'Zhou, Jie', 'Chen, Min', 'He, Wu', 'Zhang, Hai-Ying', 'Chan, Chris C. S.', 'Poon, Vincent Kwok-Man', 'Zhao, Guangyu', 'Sun, Shihui', 'Cai, Lifeng', 'Zhou, Yusen', 'Zheng, Bo-Jian', 'Jiang, Shibo']",PLoS One,,,True
6b5de60d9f674c951315c0c7549fe9e9987e239f,PMC,"Adenovirus serotype 7 associated with a severe lower respiratory tract disease outbreak in infants in Shaanxi Province, China",http://dx.doi.org/10.1186/1743-422X-8-23,PMC3030507,21241515,CC BY,"BACKGROUND: Pneumonia caused by adenovirus infection is usually severe especially with adenovirus serotype 7 commonly associated with lower respiratory tract disease outbreaks. We reported an outbreak of 70 cases of severe pneumonia with one death of infants in Shaanxi Province, China. Sampling showed adenovirus 7 (Ad7) as the primary pathogen with some co-infections. RESULTS: Two strains of adenovirus and two strains of enterovirus were isolated, the 21 pharynx swabs showed 14 positive amplifications for adenovirus; three co-infections with respiratory syncytial virus, two positive for rhinovirus, one positive for parainfluenza 3, and four negative. Adenovirus typing showed nine of the nine adenovirus positive samples were HAdV-7, three were HAdV-3 and two were too weak to perform sequencing. The entire hexon gene of adenovirus was sequenced and analyzed for the two adenovirus serotype 7 isolates, showing the nucleic acid homology was 99.8% between the two strains and 99.5% compared to the reference strain HAdV-7 (GenBank accession number AY769946). For the 21 acute phase serum samples from the 21 patients, six samples had positives results for ELISA detection of HAdV IgA, and the neutralization titers of the convalescent-phase samples were four times higher than those of the acute-phase samples in nine pairs. CONCLUSIONS: We concluded adenovirus was the viral pathogen, primarily HAdV-7, with some co-infections responsible for the outbreak. This is the first report of an infant pneumonia outbreak caused by adenovirus serotype 7 in Shaanxi Province, China.",2011 Jan 18,"['Tang, Liuying', 'Wang, Li', 'Tan, Xiaojuan', 'Xu, Wenbo']",Virol J,,,True
5206b0be1000e6c8d75a827af94c1b8e61e297c3,PMC,Travel Patterns in China,http://dx.doi.org/10.1371/journal.pone.0016364,PMC3032737,21311745,CC BY,"The spread of infectious disease epidemics is mediated by human travel. Yet human mobility patterns vary substantially between countries and regions. Quantifying the frequency of travel and length of journeys in well-defined population is therefore critical for predicting the likely speed and pattern of spread of emerging infectious diseases, such as a new influenza pandemic. Here we present the results of a large population survey undertaken in 2007 in two areas of China: Shenzhen city in Guangdong province, and Huangshan city in Anhui province. In each area, 10,000 randomly selected individuals were interviewed, and data on regular and occasional journeys collected. Travel behaviour was examined as a function of age, sex, economic status and home location. Women and children were generally found to travel shorter distances than men. Travel patterns in the economically developed Shenzhen region are shown to resemble those in developed and economically advanced middle income countries with a significant fraction of the population commuting over distances in excess of 50 km. Conversely, in the less developed rural region of Anhui, travel was much more local, with very few journeys over 30 km. Travel patterns in both populations were well-fitted by a gravity model with a lognormal kernel function. The results provide the first quantitative information on human travel patterns in modern China, and suggest that a pandemic emerging in a less developed area of rural China might spread geographically sufficiently slowly for containment to be feasible, while spatial spread in the more economically developed areas might be expected to be much more rapid, making containment more difficult.",2011 Feb 2,"['Garske, Tini', 'Yu, Hongjie', 'Peng, Zhibin', 'Ye, Min', 'Zhou, Hang', 'Cheng, Xiaowen', 'Wu, Jiabing', 'Ferguson, Neil']",PLoS One,,,True
ca0f03f52fc023762577857285184f9777dc9a27,PMC,Travel Patterns in China,http://dx.doi.org/10.1371/journal.pone.0016364,PMC3032737,21311745,CC BY,"The spread of infectious disease epidemics is mediated by human travel. Yet human mobility patterns vary substantially between countries and regions. Quantifying the frequency of travel and length of journeys in well-defined population is therefore critical for predicting the likely speed and pattern of spread of emerging infectious diseases, such as a new influenza pandemic. Here we present the results of a large population survey undertaken in 2007 in two areas of China: Shenzhen city in Guangdong province, and Huangshan city in Anhui province. In each area, 10,000 randomly selected individuals were interviewed, and data on regular and occasional journeys collected. Travel behaviour was examined as a function of age, sex, economic status and home location. Women and children were generally found to travel shorter distances than men. Travel patterns in the economically developed Shenzhen region are shown to resemble those in developed and economically advanced middle income countries with a significant fraction of the population commuting over distances in excess of 50 km. Conversely, in the less developed rural region of Anhui, travel was much more local, with very few journeys over 30 km. Travel patterns in both populations were well-fitted by a gravity model with a lognormal kernel function. The results provide the first quantitative information on human travel patterns in modern China, and suggest that a pandemic emerging in a less developed area of rural China might spread geographically sufficiently slowly for containment to be feasible, while spatial spread in the more economically developed areas might be expected to be much more rapid, making containment more difficult.",2011 Feb 2,"['Garske, Tini', 'Yu, Hongjie', 'Peng, Zhibin', 'Ye, Min', 'Zhou, Hang', 'Cheng, Xiaowen', 'Wu, Jiabing', 'Ferguson, Neil']",PLoS One,,,True
4ec2396b81441bf6b11b19a271cbc96078a8f3ce,PMC,Travel Patterns in China,http://dx.doi.org/10.1371/journal.pone.0016364,PMC3032737,21311745,CC BY,"The spread of infectious disease epidemics is mediated by human travel. Yet human mobility patterns vary substantially between countries and regions. Quantifying the frequency of travel and length of journeys in well-defined population is therefore critical for predicting the likely speed and pattern of spread of emerging infectious diseases, such as a new influenza pandemic. Here we present the results of a large population survey undertaken in 2007 in two areas of China: Shenzhen city in Guangdong province, and Huangshan city in Anhui province. In each area, 10,000 randomly selected individuals were interviewed, and data on regular and occasional journeys collected. Travel behaviour was examined as a function of age, sex, economic status and home location. Women and children were generally found to travel shorter distances than men. Travel patterns in the economically developed Shenzhen region are shown to resemble those in developed and economically advanced middle income countries with a significant fraction of the population commuting over distances in excess of 50 km. Conversely, in the less developed rural region of Anhui, travel was much more local, with very few journeys over 30 km. Travel patterns in both populations were well-fitted by a gravity model with a lognormal kernel function. The results provide the first quantitative information on human travel patterns in modern China, and suggest that a pandemic emerging in a less developed area of rural China might spread geographically sufficiently slowly for containment to be feasible, while spatial spread in the more economically developed areas might be expected to be much more rapid, making containment more difficult.",2011 Feb 2,"['Garske, Tini', 'Yu, Hongjie', 'Peng, Zhibin', 'Ye, Min', 'Zhou, Hang', 'Cheng, Xiaowen', 'Wu, Jiabing', 'Ferguson, Neil']",PLoS One,,,True
373811bcfe3a46dc6d49b2a1725f1dde8a59e8a9,PMC,"Spatial dynamics of the 1918 influenza pandemic in England, Wales and the United States",http://dx.doi.org/10.1098/rsif.2010.0216,PMC3033019,20573630,CC BY,"There is still limited understanding of key determinants of spatial spread of influenza. The 1918 pandemic provides an opportunity to elucidate spatial determinants of spread on a large scale. To better characterize the spread of the 1918 major wave, we fitted a range of city-to-city transmission models to mortality data collected for 246 population centres in England and Wales and 47 cities in the US. Using a gravity model for city-to-city contacts, we explored the effect of population size and distance on the spread of disease and tested assumptions regarding density dependence in connectivity between cities. We employed Bayesian Markov Chain Monte Carlo methods to estimate parameters of the model for population, infectivity, distance and density dependence. We inferred the most likely transmission trees for both countries. For England and Wales, a model that estimated the degree of density dependence in connectivity between cities was preferable by deviance information criterion comparison. Early in the major wave, long distance infective interactions predominated, with local infection events more likely as the epidemic became widespread. For the US, with fewer more widely dispersed cities, statistical power was lacking to estimate population size dependence or the degree of density dependence, with the preferred model depending on distance only. We find that parameters estimated from the England and Wales dataset can be applied to the US data with no likelihood penalty.",2011 Feb 6,"['Eggo, Rosalind M.', 'Cauchemez, Simon', 'Ferguson, Neil M.']",J R Soc Interface,,,True
cf85ce2e8400011f5119b0eb1a87ffb7933b84a1,PMC,Contribution of complement activation pathways to neuropathology differs among mouse models of Alzheimer's disease,http://dx.doi.org/10.1186/1742-2094-8-4,PMC3033336,21235806,CC BY,"BACKGROUND: Complement proteins and activation products have been found associated with neuropathology in Alzheimer's disease (AD). Recently, a C5a receptor antagonist was shown to suppress neuropathology in two murine models of AD, Tg2576 and 3xTg. Previously, a genetic deficiency of C1q in the Tg2576 mouse model showed an accumulation of fibrillar plaques similar to the complement sufficient Tg2576, but reactive glia were significantly decreased and neuronal integrity was improved suggesting detrimental consequences for complement activation in AD. The goal of this study was to define the role of the classical complement activation pathway in the progression of pathology in the 3xTg mouse that develops tangles in addition to fibrillar plaques (more closely reflecting human AD pathology) and to assess the influence of complement in a model of AD with a higher level of complement hemolytic activity. METHODS: 3xTg mice deficient in C1q (3xTgQ-/-) were generated, and both 3xTg and 3xTgQ-/- were backcrossed to the BUB mouse strain which has higher in vitro hemolytic complement activity. Mice were aged and perfused, and brain sections stained for pathological markers or analyzed for proinflammatory marker expression. RESULTS: 3xTgQ-/- mice showed similar amounts of fibrillar amyloid, reactive glia and hyperphosphorylated tau as the C1q-sufficient 3xTg at the ages analyzed. However, 3xTg and 3xTgQ-/- on the BUB background developed pathology earlier than on the original 3xTg background, although the presence of C1q had no effect on neuropathological and pro-inflammatory markers. In contrast to that seen in other transgenic models of AD, C1q, C4 and C3 immunoreactivity was undetectable on the plaques of 3xTg in any background, although C3 was associated with reactive astrocytes surrounding the plaques. Importantly, properdin a component of the alternative complement pathway was associated with plaques in all models. CONCLUSIONS: In contrast to previously investigated transgenic models of AD, development of neuropathology in 3xTg mice, which progresses much slower than other murine models, may not be influenced by fibrillar amyloid mediated activation of the classical complement pathway, suggesting that the alternative complement pathway activation or a C3-independent cleavage of C5 could account for the detrimental effects in these mice that are prevented by the C5a receptor antagonist. Furthermore, the paucity of complement activation may be a factor in the slower kinetics of progression of pathology in the 3xTg model of this disease.",2011 Jan 15,"['Fonseca, Maria I', 'Chu, Shu-Hui', 'Berci, Alisia M', 'Benoit, Marie E', 'Peters, Douglas G', 'Kimura, Yuko', 'Tenner, Andrea J']",J Neuroinflammation,,,True
b708da1945a7a42cd61526e043d527592d4d9518,PMC,Charge-Surrounded Pockets and Electrostatic Interactions with Small Ions Modulate the Activity of Retroviral Fusion Proteins,http://dx.doi.org/10.1371/journal.ppat.1001268,PMC3033372,21304939,CC BY,"Refolding of viral class-1 membrane fusion proteins from a native state to a trimer-of-hairpins structure promotes entry of viruses into cells. Here we present the structure of the bovine leukaemia virus transmembrane glycoprotein (TM) and identify a group of asparagine residues at the membrane-distal end of the trimer-of-hairpins that is strikingly conserved among divergent viruses. These asparagines are not essential for surface display of pre-fusogenic envelope. Instead, substitution of these residues dramatically disrupts membrane fusion. Our data indicate that, through electrostatic interactions with a chloride ion, the asparagine residues promote assembly and profoundly stabilize the fusion-active structures that are required for viral envelope-mediated membrane fusion. Moreover, the BLV TM structure also reveals a charge-surrounded hydrophobic pocket on the central coiled coil and interactions with basic residues that cluster around this pocket are critical to membrane fusion and form a target for peptide inhibitors of envelope function. Charge-surrounded pockets and electrostatic interactions with small ions are common among class-1 fusion proteins, suggesting that small molecules that specifically target such motifs should prevent assembly of the trimer-of-hairpins and be of value as therapeutic inhibitors of viral entry.",2011 Feb 3,"['Lamb, Daniel', 'Schüttelkopf, Alexander W.', 'van Aalten, Daan M. F.', 'Brighty, David W.']",PLoS Pathog,,,True
12fe4cca998a403e153ae872595eab2676c77d2f,PMC,Phenotypic characteristics of human type II alveolar epithelial cells suitable for antigen presentation to T lymphocytes,http://dx.doi.org/10.1186/1465-9921-12-15,PMC3033824,21261956,CC BY,"BACKGROUND: Type II alveolar epithelial cells (AECII) are well known for their role in the innate immune system. More recently, it was proposed that they could play a role in the antigen presentation to T lymphocytes but contradictory results have been published both concerning their surface expressed molecules and the T lymphocyte responses in mixed lymphocyte cultures. The use of either AECII cell line or fresh cells could explain the observed discrepancies. Thus, this study aimed at defining the most relevant model of accessory antigen presenting cells by carefully comparing the two models for their expression of surface molecules necessary for efficient antigen presentation. METHODS: We have compared by flow cytometry the surface expression of the major markers involved in the immunological synapse on the A549 cell line, the most popular model of type II alveolar epithelial cells, and freshly isolated cells. HLA-DR, CD80, CD86, ICOS-L, CD54, CD58 surface expression were studied in resting conditions as well as after IFN-γ/TNF-α treatment, two inflammatory cytokines, known to modulate some of these markers. RESULTS: The major difference found between the two cells types was the very low surface expression of HLA-DR on the A549 cell line compared to its constitutive expression on freshly isolated AECII. The surface expression of co-stimulatory molecules from the B7 family was very low for the CD86 (B7-2) and ICOS-L (B7-H2) and absent for CD80 (B7-1) on both freshly isolated cells and A549 cell line. Neither IFN-γ nor TNF-α could increase the expression of these classical co-stimulatory molecules. However CD54 (ICAM-1) and CD58 (LFA-3) adhesion molecules, known to be implicated in B7 independent co-stimulatory signals, were well expressed on the two cell types. CONCLUSIONS: Constitutive expression of MHC class I and II molecules as well as alternative co-stimulatory molecules by freshly isolated AECII render these cells a good model to study antigen presentation.",2011 Jan 24,"['Corbière, Véronique', 'Dirix, Violette', 'Norrenberg, Sarah', 'Cappello, Mattéo', 'Remmelink, Myriam', 'Mascart, Françoise']",Respir Res,,,True
3b9e6b4d9ba3f58a882e5e25dd12d8aed9b5b4d4,PMC,Are there any differences in clinical and laboratory findings on admission between H1N1 positive and negative patients with flu-like symptoms?,http://dx.doi.org/10.1186/1756-0500-4-4,PMC3035198,21214902,CC BY,"BACKGROUND: The World Health Organization alert for the H1N1 influenza pandemic led to the implementation of certain measures regarding admission of patients with flu-like symptoms. All these instructions were adopted by the Greek National Health System. The aim of this study was to retrospectively examine the characteristics of all subjects admitted to the Unit of Infectious Diseases with symptoms indicating H1N1 infection, and to identify any differences between H1N1 positive or negative patients. Patients from the ED (emergency department) with flu-like symptoms (sore throat, cough, rhinorhea, or nasal congestion) and fever >37.5°C were admitted in the Unit of Infectious diseases and gave pharyngeal or nasopharyngeal swabs. Swabs were tested with real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR). FINDINGS: Patients were divided into two groups. Group A comprised 33 H1N1 positive patients and Group B (control group) comprised of 27 H1N1 negative patients. The two groups did not differ in terms of patient age, co-morbidities, length of hospitalization, temperature elevation, hypoxemia, as well as renal and liver function. There were also no significant differences in severity on admission. C-reactive protein (CRP) (mean 12.8 vs. 5.74) and white blood count (WBC) (mean 10.528 vs. 7.114) were significantly higher in group B than in group A upon admission. Obesity was noted in 8 patients of Group A (mean 31.67) and 14 patients of Group B (mean 37.78). Body mass index (BMI) was lower in H1N1 positive than in H1N1 negative patients (mean 31.67 vs. 37.78, respectively; p = 0.009). CONCLUSIONS: The majority of patients in both groups were young male adults. CRP, WBC and BMI were higher among H1N1 negative patients. Finally, clinical course of patients in both groups was mild and uneventful.",2011 Jan 7,"['Zarogoulidis, Paul', 'Constantinidis, Theodoros', 'Steiropoulos, Paschalis', 'Papanas, Nikolaos', 'Zarogoulidis, Kostas', 'Maltezos, Efstratios']",BMC Res Notes,,,True
9e0f14131900d5136cabf11f654a5cbb9d88ad48,PMC,Further Characterisation of the Translational Termination-Reinitiation Signal of the Influenza B Virus Segment 7 RNA,http://dx.doi.org/10.1371/journal.pone.0016822,PMC3035654,21347434,CC BY,"Termination-dependent reinitiation is used to co-ordinately regulate expression of the M1 and BM2 open-reading frames (ORFs) of the dicistronic influenza B segment 7 RNA. The start codon of the BM2 ORF overlaps the stop codon of the M1 ORF in the pentanucleotide UAA UG and ∼10% of ribosomes terminating at the M1 stop codon reinitiate translation at the overlapping AUG. BM2 synthesis requires the presence of, and translation through, 45 nt of RNA immediately upstream of the UAA UG, known as the ‘termination upstream ribosome binding site’ (TURBS). This region may tether ribosomal 40S subunits to the mRNA following termination and a short region of the TURBS, motif 1, with complementarity to helix 26 of 18S rRNA has been implicated in this process. Here, we provide further evidence for a direct interaction between mRNA and rRNA using antisense oligonucleotide targeting and functional analysis in yeast cells. The TURBS also binds initiation factor eIF3 and we show here that this protein stimulates reinitiation from both wild-type and defective TURBS when added exogenously, perhaps by stabilising ribosome-mRNA interactions. Further, we show that the position of the TURBS with respect to the UAA UG overlap is crucial, and that termination too far downstream of the 18S complementary sequence inhibits the process, probably due to reduced 40S tethering. However, in reporter mRNAs where the restart codon alone is moved downstream, termination-reinitiation is inhibited but not abolished, thus the site of reinitiation is somewhat flexible. Reinitiation on distant AUGs is not inhibited in eIF4G-depleted RRL, suggesting that the tethered 40S subunit can move some distance without a requirement for linear scanning.",2011 Feb 8,"['Powell, Michael L.', 'Leigh, Kendra E.', 'Pöyry, Tuija A. A.', 'Jackson, Richard J.', 'Brown, T. David K.', 'Brierley, Ian']",PLoS One,,,True
49ef14fbeee682057ed14674f623ca36c6d954cc,PMC,"RNA and DNA Bacteriophages as Molecular Diagnosis Controls in Clinical Virology: A Comprehensive Study of More than 45,000 Routine PCR Tests",http://dx.doi.org/10.1371/journal.pone.0016142,PMC3036576,21347398,CC BY,"Real-time PCR techniques are now commonly used for the detection of viral genomes in various human specimens and require for validation both external and internal controls (ECs and ICs). In particular, ICs added to clinical samples are necessary to monitor the extraction, reverse transcription, and amplification steps in order to detect false-negative results resulting from PCR-inhibition or errors in the technical procedure. Here, we performed a large scale evaluation of the use of bacteriophages as ICs in routine molecular diagnosis. This allowed to propose simple standardized procedures (i) to design specific ECs for both DNA and RNA viruses and (ii) to use T4 (DNA) or MS2 (RNA) phages as ICs in routine diagnosis. Various technical formats for using phages as ICs were optimised and validated. Subsequently, T4 and MS2 ICs were evaluated in routine real-time PCR or RT-PCR virological diagnostic tests, using a series of 8,950 clinical samples (representing 36 distinct specimen types) sent to our laboratory for the detection of a variety of DNA and RNA viruses. The frequency of inefficient detection of ICs was analyzed according to the nature of the sample. Inhibitors of enzymatic reactions were detected at high frequency in specific sample types such as heparinized blood and bone marrow (>70%), broncho-alveolar liquid (41%) and stools (36%). The use of T4 and MS2 phages as ICs proved to be cost-effective, flexible and adaptable to various technical procedures of real-time PCR detection in virology. It represents a valuable strategy for enhancing the quality of routine molecular diagnosis in laboratories that use in-house designed diagnostic systems, which can conveniently be associated to the use of specific synthetic ECs. The high rate of inhibitors observed in a variety of specimen types should stimulate the elaboration of improved technical protocols for the extraction and amplification of nucleic acids.",2011 Feb 9,"['Ninove, Laetitia', 'Nougairede, Antoine', 'Gazin, Celine', 'Thirion, Laurence', 'Delogu, Ilenia', 'Zandotti, Christine', 'Charrel, Remi N.', 'De Lamballerie, Xavier']",PLoS One,,,True
eb0fb44015f899d2b00fc41e9e65ea13fc7fcde1,PMC,Estimating the Economic Impact of Climate Change on Cardiovascular Diseases—Evidence from Taiwan,http://dx.doi.org/10.3390/ijerph7124250,PMC3037052,21318006,CC BY,"The main purpose of this study was to investigate how climate change affects blood vessel-related heart disease and hypertension and to estimate the associated economic damage. In this paper, both the panel data model and the contingent valuation method (CVM) approaches are applied. The empirical results indicate that the number of death from cardiovascular diseases would be increased by 0.226% as the variation in temperature increases by 1%. More importantly, the number of death from cardiovascular diseases would be increased by 1.2% to 4.1% under alternative IPCC climate change scenarios. The results from the CVM approach show that each person would be willing to pay US$51 to US$97 per year in order to avoid the increase in the mortality rate of cardiovascular diseases caused by climate change.",2010 Dec 17,"['Liao, Shu-Yi', 'Tseng, Wei-Chun', 'Chen, Pin-Yu', 'Chen, Chi-Chung', 'Wu, Wei-Min']",Int J Environ Res Public Health,,,True
4f3a25f455f5b0a76e0379e91f028a69de4be389,PMC,Knowledge and attitudes of healthcare workers in Chinese intensive care units regarding 2009 H1N1 influenza pandemic,http://dx.doi.org/10.1186/1471-2334-11-24,PMC3037318,21266085,CC BY,"BACKGROUND: To describe the knowledge and attitudes of critical care clinicians during the 2009 H1N1 influenza pandemic. METHODS: A survey conducted in 21 intensive care units in 17 provinces in China. RESULTS: Out of 733 questionnaires distributed, 695 were completed. Three hundred and fifty-six respondents (51.2%) reported their experience of caring for H1N1 patients. Despite the fact that 88.5% of all respondents ultimately finished an H1N1 training program, only 41.9% admitted that they had the knowledge of 2009 H1N1 influenza. A total of 572 respondents (82.3%) expressed willingness to care for H1N1 patients. Independent variables associated with increasing likelihood to care for patients in the logistic regression analysis were physicians or nurses rather than other professionals (odds ratio 4.056 and 3.235, p = 0.002 and 0.007, respectively), knowledge training prior to patient care (odds ratio 1.531, p = 0.044), and the confidence to know how to protect themselves and their patients (odds ratio 2.109, p = 0.001). CONCLUSION: Critical care clinicians reported poor knowledge of H1N1 influenza, even though most finished a relevant knowledge training program. Implementation of appropriate education program might improve compliance to infection control measures, and willingness to work in a pandemic.",2011 Jan 25,"['Ma, Xiaochun', 'He, Zhenyang', 'Wang, Yushan', 'Jiang, Li', 'Xu, Yuan', 'Qian, Chuanyun', 'Sun, Rongqing', 'Chen, Erzhen', 'Hu, Zhenjie', 'Zhou, Lihua', 'Zhou, Fachun', 'Qin, Tiehe', 'Cao, Xiangyuan', 'An, Youzhong', 'Sun, Renhua', 'Zhang, Xijing', 'Lin, Jiandong', 'Ai, Yuhang', 'Wu, Dawei', 'Du, Bin']",BMC Infect Dis,,,True
9bff285847e6573b613d937df23f57355afcbd5f,PMC,NS2 Protein of Hepatitis C Virus Interacts with Structural and Non-Structural Proteins towards Virus Assembly,http://dx.doi.org/10.1371/journal.ppat.1001278,PMC3037360,21347350,CC BY,"Growing experimental evidence indicates that, in addition to the physical virion components, the non-structural proteins of hepatitis C virus (HCV) are intimately involved in orchestrating morphogenesis. Since it is dispensable for HCV RNA replication, the non-structural viral protein NS2 is suggested to play a central role in HCV particle assembly. However, despite genetic evidences, we have almost no understanding about NS2 protein-protein interactions and their role in the production of infectious particles. Here, we used co-immunoprecipitation and/or fluorescence resonance energy transfer with fluorescence lifetime imaging microscopy analyses to study the interactions between NS2 and the viroporin p7 and the HCV glycoprotein E2. In addition, we used alanine scanning insertion mutagenesis as well as other mutations in the context of an infectious virus to investigate the functional role of NS2 in HCV assembly. Finally, the subcellular localization of NS2 and several mutants was analyzed by confocal microscopy. Our data demonstrate molecular interactions between NS2 and p7 and E2. Furthermore, we show that, in the context of an infectious virus, NS2 accumulates over time in endoplasmic reticulum-derived dotted structures and colocalizes with both the envelope glycoproteins and components of the replication complex in close proximity to the HCV core protein and lipid droplets, a location that has been shown to be essential for virus assembly. We show that NS2 transmembrane region is crucial for both E2 interaction and subcellular localization. Moreover, specific mutations in core, envelope proteins, p7 and NS5A reported to abolish viral assembly changed the subcellular localization of NS2 protein. Together, these observations indicate that NS2 protein attracts the envelope proteins at the assembly site and it crosstalks with non-structural proteins for virus assembly.",2011 Feb 10,"['Popescu, Costin-Ioan', 'Callens, Nathalie', 'Trinel, Dave', 'Roingeard, Philippe', 'Moradpour, Darius', 'Descamps, Véronique', 'Duverlie, Gilles', 'Penin, François', 'Héliot, Laurent', 'Rouillé, Yves', 'Dubuisson, Jean']",PLoS Pathog,,,True
86239535bbc306bd90a85a6145840c784fa35d82,PMC,Mitigation Strategies for Pandemic Influenza A: Balancing Conflicting Policy Objectives,http://dx.doi.org/10.1371/journal.pcbi.1001076,PMC3037387,21347316,CC BY,"Mitigation of a severe influenza pandemic can be achieved using a range of interventions to reduce transmission. Interventions can reduce the impact of an outbreak and buy time until vaccines are developed, but they may have high social and economic costs. The non-linear effect on the epidemic dynamics means that suitable strategies crucially depend on the precise aim of the intervention. National pandemic influenza plans rarely contain clear statements of policy objectives or prioritization of potentially conflicting aims, such as minimizing mortality (depending on the severity of a pandemic) or peak prevalence or limiting the socio-economic burden of contact-reducing interventions. We use epidemiological models of influenza A to investigate how contact-reducing interventions and availability of antiviral drugs or pre-pandemic vaccines contribute to achieving particular policy objectives. Our analyses show that the ideal strategy depends on the aim of an intervention and that the achievement of one policy objective may preclude success with others, e.g., constraining peak demand for public health resources may lengthen the duration of the epidemic and hence its economic and social impact. Constraining total case numbers can be achieved by a range of strategies, whereas strategies which additionally constrain peak demand for services require a more sophisticated intervention. If, for example, there are multiple objectives which must be achieved prior to the availability of a pandemic vaccine (i.e., a time-limited intervention), our analysis shows that interventions should be implemented several weeks into the epidemic, not at the very start. This observation is shown to be robust across a range of constraints and for uncertainty in estimates of both R(0) and the timing of vaccine availability. These analyses highlight the need for more precise statements of policy objectives and their assumed consequences when planning and implementing strategies to mitigate the impact of an influenza pandemic.",2011 Feb 10,"['Hollingsworth, T. Déirdre', 'Klinkenberg, Don', 'Heesterbeek, Hans', 'Anderson, Roy M.']",PLoS Comput Biol,,,True
4049f899668ea1ad76af00572962f030bae13756,PMC,Mitigation Strategies for Pandemic Influenza A: Balancing Conflicting Policy Objectives,http://dx.doi.org/10.1371/journal.pcbi.1001076,PMC3037387,21347316,CC BY,"Mitigation of a severe influenza pandemic can be achieved using a range of interventions to reduce transmission. Interventions can reduce the impact of an outbreak and buy time until vaccines are developed, but they may have high social and economic costs. The non-linear effect on the epidemic dynamics means that suitable strategies crucially depend on the precise aim of the intervention. National pandemic influenza plans rarely contain clear statements of policy objectives or prioritization of potentially conflicting aims, such as minimizing mortality (depending on the severity of a pandemic) or peak prevalence or limiting the socio-economic burden of contact-reducing interventions. We use epidemiological models of influenza A to investigate how contact-reducing interventions and availability of antiviral drugs or pre-pandemic vaccines contribute to achieving particular policy objectives. Our analyses show that the ideal strategy depends on the aim of an intervention and that the achievement of one policy objective may preclude success with others, e.g., constraining peak demand for public health resources may lengthen the duration of the epidemic and hence its economic and social impact. Constraining total case numbers can be achieved by a range of strategies, whereas strategies which additionally constrain peak demand for services require a more sophisticated intervention. If, for example, there are multiple objectives which must be achieved prior to the availability of a pandemic vaccine (i.e., a time-limited intervention), our analysis shows that interventions should be implemented several weeks into the epidemic, not at the very start. This observation is shown to be robust across a range of constraints and for uncertainty in estimates of both R(0) and the timing of vaccine availability. These analyses highlight the need for more precise statements of policy objectives and their assumed consequences when planning and implementing strategies to mitigate the impact of an influenza pandemic.",2011 Feb 10,"['Hollingsworth, T. Déirdre', 'Klinkenberg, Don', 'Heesterbeek, Hans', 'Anderson, Roy M.']",PLoS Comput Biol,,,False
bf1b9188ca2e3eb5e80b73dcf3c12799344a7199,PMC,"Short Term Effects of Weather on Hand, Foot and Mouth Disease",http://dx.doi.org/10.1371/journal.pone.0016796,PMC3037951,21347303,CC BY,"BACKGROUND: Hand, foot, and mouth disease (HFMD) outbreaks leading to clinical and fatal complications have increased since late 1990s; especially in the Asia Pacific Region. Outbreaks of HFMD peaks in the warmer season of the year, but the underlying factors for this annual pattern and the reasons to the recent upsurge trend have not yet been established. This study analyzed the effect of short-term changes in weather on the incidence of HFMD in Singapore. METHODS: The relative risks between weekly HFMD cases and temperature and rainfall were estimated for the period 2001–2008 using time series Poisson regression models allowing for over-dispersion. Smoothing was used to allow non-linear relationship between weather and weekly HFMD cases, and to adjust for seasonality and long-term time trend. Additionally, autocorrelation was controlled and weather was allowed to have a lagged effect on HFMD incidence up to 2 weeks. RESULTS: Weekly temperature and rainfall showed statistically significant association with HFMD incidence at time lag of 1–2 weeks. Every 1°C increases in maximum temperature above 32°C elevated the risk of HFMD incidence by 36% (95% CI = 1.341–1.389). Simultaneously, one mm increase of weekly cumulative rainfall below 75 mm increased the risk of HFMD by 0.3% (CI = 1.002–1.003). While above 75 mm the effect was opposite and each mm increases of rainfall decreased the incidence by 0.5% (CI = 0.995–0.996). We also found that a difference between minimum and maximum temperature greater than 7°C elevated the risk of HFMD by 41% (CI = 1.388–1.439). CONCLUSION: Our findings suggest a strong association between HFMD and weather. However, the exact reason for the association is yet to be studied. Information on maximum temperature above 32°C and moderate rainfall precede HFMD incidence could help to control and curb the up-surging trend of HFMD.",2011 Feb 11,"['Hii, Yien Ling', 'Rocklöv, Joacim', 'Ng, Nawi']",PLoS One,,,True
4c6a45d1e56660fa713b637825b96e287a0acef5,PMC,Experimental infection of dogs with a feline endogenous retrovirus RD-114,http://dx.doi.org/10.1186/1751-0147-53-3,PMC3038973,21269522,CC BY,"BACKGROUND: The feline endogenous retrovirus RD114 is contained in the genome of cats. The virus may contaminate live canine vaccines based on cultured feline cells. The in vivo infectivity, acute and subacute pathogenicity, and viral proliferation of the RD114 virus were evaluated by experimental infection of dogs. METHODS: Nine specific pathogen free dogs were divided into three groups, with each group consisting of one female and two male dogs. Dogs were subcutaneously inoculated in the neck with either 1 ml RD114 stock virus (group A), inactivated RD114 virus suspension (group B), or cell culture medium (group C) as a negative control. To assess blood cell counts and biochemical properties, blood samples from each group were collected 5 days before inoculation, just prior to inoculation, and 1, 3, 7 and 10 days post-inoculation. RESULT: During the experimental period of 51 days, none of the dogs inoculated with RD114 virus showed any clinical signs, significant increases in rectal temperature or abnormal blood biochemical characteristics including C-reactive protein when compared with the negative controls. We were not able to re-isolate the RD114 virus from buffy coat cells of group A dogs. Additionally, we could not detect RD114 provirus in the genomic DNA isolated from peripheral blood leukocytes, lymph node, spleen and sternal bone marrow cells. CONCLUSIONS: Signs of RD114 virus proliferation were not found after subcutaneous infection of dogs. Although the potential risk caused by infection with RD114 virus in dogs could not be assessed in this study, we suspect that RD114 virus has little or no virulence in dogs.",2011 Jan 27,"['Narushima, Rie', 'Horiuchi, Noriyuki', 'Usui, Tatsufumi', 'Ogawa, Takashi', 'Takahashi, Toshio', 'Shimazaki, Tomoaki']",Acta Vet Scand,,,True
cfb06153bd9db651c6c7c268aecf6e65113fe008,PMC,PLP2 of Mouse Hepatitis Virus A59 (MHV-A59) Targets TBK1 to Negatively Regulate Cellular Type I Interferon Signaling Pathway,http://dx.doi.org/10.1371/journal.pone.0017192,PMC3041802,21364999,CC BY,"BACKGROUND: Coronaviruses such as severe acute respiratory syndrome (SARS) coronavirus (SCoV) and mouse hepatitis virus A59 (MHV-A59) have evolved strategies to disable the innate immune system for productive replication and spread of infection. We have previously shown that papain-like protease domain 2 (PLP2), a catalytic domain of the nonstructural protein 3 (nsp3) of MHV-A59, encodes a deubiquitinase (DUB) and inactivates IFN regulatory factor 3 (IRF3) thereby the type I interferon (IFN) response. PRINCIPAL FINDINGS: Here we provide further evidence that PLP2 may also target TANK-binding kinase-1 (TBK1), the upstream kinase of IRF3 in the IFN signaling pathway. Overexpression experiments showed that PLP2 deubiquitinated TBK1 and reduced its kinase activity, hence inhibited IFN-β reporter activity. Albeit promiscuous in deubiquitinating cellular proteins, PLP2 inactivated TBK1 and IFN-β response in TNF receptor associated factor 3 (TRAF3) deficient cells, suggesting that targeting TBK1 would be sufficient for PLP2 to inhibit IRF3 activation. This notion was further supported by in vitro kinase assays, in which prior treatment of TBK1 with PLP2 inhibited its kinase activity to phosphorylate IRF3. Intriguing enough, results of PLP2 overexpression system and MHV-A59 infection system proved that PLP2 formed an inactive complex with TBK1 and IRF3 in the cytoplasm and the presence of PLP2 stabilized the hypo-phosphorylated IRF3-TBK1 complex in a dose-dependent manner. CONCLUSIONS: These results suggest that PLP2 not only inactivates TBK1, but also prevents IRF3 nuclear translocation hence inhibits IFN transcription activation. Identification of the conserved DUB activity of PLP2 in suppression of IFN signaling would provide a useful clue to the development of therapeutics against coronaviruses infection.",2011 Feb 18,"['Wang, Gang', 'Chen, Gang', 'Zheng, Dahai', 'Cheng, Genhong', 'Tang, Hong']",PLoS One,,,True
6606f7964096d15ffdcb9772acbe40ae415dcb97,PMC,Update on the management of acute pharyngitis in children,http://dx.doi.org/10.1186/1824-7288-37-10,PMC3042010,21281502,CC BY,"Streptococcal pharyngitis is a very common pathology in paediatric age all over the world. Nevertheless there isn't a joint agreement on the management of this condition. Some authors recommend to perform a microbiological investigation in suspected bacterial cases in order to treat the confirmed cases with antibiotics so to prevent suppurative complications and acute rheumatic fever. Differently, other authors consider pharyngitis, even streptococcal one, a benign, self-limiting disease. Consequently they wouldn't routinely perform microbiological tests and, pointing to a judicious use of antibiotics, they would reserve antimicrobial treatment to well-selected cases. It has been calculated that the number of patients needed to treat to prevent one complication after upper respiratory tract infections (including sore throat), was over 4000. Even the use of the Centor score, in order to evaluate the risk of streptococcal infection, is under debate and the interpretation of the test results may vary considerably. Penicillin is considered all over the world as first line treatment, but oral amoxicillin is also accepted and, due to its better palatability, can be a suitable option. Macrolides should be reserved to the rare cases of proved allergy to β-lactams. Cephalosporins can be used in patients allergic to penicillin (with the exception of type I hypersensibility) and have been also proposed to treat the relapses.",2011 Jan 31,"['Regoli, Marta', 'Chiappini, Elena', 'Bonsignori, Francesca', 'Galli, Luisa', 'de Martino, Maurizio']",Ital J Pediatr,,,True
2a90543a82ae4b2916e12f6294b7a37aa8142942,PMC,Twelve years' detection of respiratory viruses by immunofluorescence in hospitalised children: impact of the introduction of a new respiratory picornavirus assay,http://dx.doi.org/10.1186/1471-2334-11-41,PMC3044667,21299840,CC BY,"BACKGROUND: Direct immunofluorescence assays (DFA) are a rapid and inexpensive method for the detection of respiratory viruses and may therefore be used for surveillance. Few epidemiological studies have been published based solely on DFA and none included respiratory picornaviruses and human metapneumovirus (hMPV). We wished to evaluate the use of DFA for epidemiological studies with a long-term observation of respiratory viruses that includes both respiratory picornaviruses and hMPV. METHODS: Since 1998 all children hospitalized with respiratory illness at the University Hospital Bern have been screened with DFA for common respiratory viruses including adenovirus, respiratory syncytial virus (RSV), influenza A and B, and parainfluenza virus 1-3. In 2006 assays for respiratory picornaviruses and hMPV were added. Here we describe the epidemiological pattern for these respiratory viruses detected by DFA in 10'629 nasopharyngeal aspirates collected from 8'285 patients during a 12-year period (1998-2010). RESULTS: Addition of assays for respiratory picornaviruses and hMPV raised the proportion of positive DFA results from 35% to 58% (p < 0.0001). Respiratory picornaviruses were the most common viruses detected among patients ≥1 year old. The seasonal patterns and age distribution for the studied viruses agreed well with those reported in the literature. In 2010, an hMPV epidemic of unexpected size was observed. CONCLUSIONS: DFA is a valid, rapid, flexible and inexpensive method. The addition of assays for respiratory picornaviruses and hMPV broadens its range of viral detection. DFA is, even in the ""PCR era"", a particularly adapted method for the long term surveillance of respiratory viruses in a pediatric population.",2011 Feb 7,"['Sadeghi, Christine D', 'Aebi, Christoph', 'Gorgievski-Hrisoho, Meri', 'Mühlemann, Kathrin', 'Barbani, Maria Teresa']",BMC Infect Dis,,,True
ac99b803a90e235412c73efa91894e9a1ed3f019,PMC,NIH Disease Funding Levels and Burden of Disease,http://dx.doi.org/10.1371/journal.pone.0016837,PMC3044706,21383981,CC BY,"BACKGROUND: An analysis of NIH funding in 1996 found that the strongest predictor of funding, disability-adjusted life-years (DALYs), explained only 39% of the variance in funding. In 1998, Congress requested that the Institute of Medicine (IOM) evaluate priority-setting criteria for NIH funding; the IOM recommended greater consideration of disease burden. We examined whether the association between current burden and funding has changed since that time. METHODS: We analyzed public data on 2006 NIH funding for 29 common conditions. Measures of US disease burden in 2004 were obtained from the World Health Organization's Global Burden of Disease study and national databases. We assessed the relationship between disease burden and NIH funding dollars in univariate and multivariable log-linear models that evaluated all measures of disease burden. Sensitivity analyses examined associations with future US burden, current and future measures of world disease burden, and a newly standardized NIH accounting method. RESULTS: In univariate and multivariable analyses, disease-specific NIH funding levels increased with burden of disease measured in DALYs (p = 0.001), which accounted for 33% of funding level variation. No other factor predicted funding in multivariable models. Conditions receiving the most funding greater than expected based on disease burden were AIDS ($2474 M), diabetes mellitus ($390 M), and perinatal conditions ($297 M). Depression ($719 M), injuries ($691 M), and chronic obstructive pulmonary disease ($613 M) were the most underfunded. Results were similar using estimates of future US burden, current and future world disease burden, and alternate NIH accounting methods. CONCLUSIONS: Current levels of NIH disease-specific research funding correlate modestly with US disease burden, and correlation has not improved in the last decade.",2011 Feb 24,"['Gillum, Leslie A.', 'Gouveia, Christopher', 'Dorsey, E. Ray', 'Pletcher, Mark', 'Mathers, Colin D.', 'McCulloch, Charles E.', 'Johnston, S. Claiborne']",PLoS One,,,True
164f0fed97b05b34ea5df0f4e4e9e204d05f7849,PMC,Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes,http://dx.doi.org/10.1371/journal.pone.0017324,PMC3044746,21390319,CC BY,"This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. In addition, APOM gene function was further characterized to elucidate its activity in cholesterol metabolism. Seventeen APOM SNPs documented in the NCBI database were genotyped. Five SNPs were confirmed in our study cohort of 1234 T2D and 606 control participants. Three of the five SNPs rs707921(C+1871A), rs707922(G+1837T) and rs805264(G+203A) were in linkage disequilibrium (LD). We chose rs707922 to tag this LD region for down stream association analyses and characterized the function of this SNP at molecular level. No association between APOM and T2D susceptibility was detected in our Hong Kong Chinese cohort. Interestingly, the C allele of rs805297 was significantly associated with T2D duration of longer than 10 years (OR = 1.245, p = 0.015). The rs707922 TT genotype was significantly associated with elevated plasma total- and LDL- cholesterol levels (p = 0.006 and p = 0.009, respectively) in T2D patients. Molecular analyses of rs707922 lead to the discoveries of a novel transcript APOM5 as well as the cryptic nature of exon 5 of the gene. Ectopic expression of APOM5 transcript confirmed rs707922 allele-dependent activity of the transcript in modifying cholesterol homeostasis in vitro. In conclusion, the results here did not support APOM as a T2D susceptibility gene in Hong Kong Chinese. However, in T2D patients, a subset of APOM SNPs was associated with disease duration and metabolic traits. Further molecular analysis proved the functional activity of rs707922 in APOM expression and in regulation of cellular cholesterol content.",2011 Feb 24,"['Zhou, Jun-Wei', 'Tsui, Stephen K. W.', 'Ng, Maggie C. Y.', 'Geng, Hua', 'Li, Sai-Kam', 'So, Wing-Yee', 'Ma, Ronald C.', 'Wang, Ying', 'Tao, Qian', 'Chen, Zhen-Yu', 'Chan, Juliana C. N.', 'Ho, Yuan-Yuan']",PLoS One,,,True
4594720a38546b67cb9a8f2ec9e9a7bee2620e78,PMC,Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes,http://dx.doi.org/10.1371/journal.pone.0017324,PMC3044746,21390319,CC BY,"This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. In addition, APOM gene function was further characterized to elucidate its activity in cholesterol metabolism. Seventeen APOM SNPs documented in the NCBI database were genotyped. Five SNPs were confirmed in our study cohort of 1234 T2D and 606 control participants. Three of the five SNPs rs707921(C+1871A), rs707922(G+1837T) and rs805264(G+203A) were in linkage disequilibrium (LD). We chose rs707922 to tag this LD region for down stream association analyses and characterized the function of this SNP at molecular level. No association between APOM and T2D susceptibility was detected in our Hong Kong Chinese cohort. Interestingly, the C allele of rs805297 was significantly associated with T2D duration of longer than 10 years (OR = 1.245, p = 0.015). The rs707922 TT genotype was significantly associated with elevated plasma total- and LDL- cholesterol levels (p = 0.006 and p = 0.009, respectively) in T2D patients. Molecular analyses of rs707922 lead to the discoveries of a novel transcript APOM5 as well as the cryptic nature of exon 5 of the gene. Ectopic expression of APOM5 transcript confirmed rs707922 allele-dependent activity of the transcript in modifying cholesterol homeostasis in vitro. In conclusion, the results here did not support APOM as a T2D susceptibility gene in Hong Kong Chinese. However, in T2D patients, a subset of APOM SNPs was associated with disease duration and metabolic traits. Further molecular analysis proved the functional activity of rs707922 in APOM expression and in regulation of cellular cholesterol content.",2011 Feb 24,"['Zhou, Jun-Wei', 'Tsui, Stephen K. W.', 'Ng, Maggie C. Y.', 'Geng, Hua', 'Li, Sai-Kam', 'So, Wing-Yee', 'Ma, Ronald C.', 'Wang, Ying', 'Tao, Qian', 'Chen, Zhen-Yu', 'Chan, Juliana C. N.', 'Ho, Yuan-Yuan']",PLoS One,,,False
47025519790a04e4fae85f0b8d3b6f0949d9294f,PMC,Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes,http://dx.doi.org/10.1371/journal.pone.0017324,PMC3044746,21390319,CC BY,"This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. In addition, APOM gene function was further characterized to elucidate its activity in cholesterol metabolism. Seventeen APOM SNPs documented in the NCBI database were genotyped. Five SNPs were confirmed in our study cohort of 1234 T2D and 606 control participants. Three of the five SNPs rs707921(C+1871A), rs707922(G+1837T) and rs805264(G+203A) were in linkage disequilibrium (LD). We chose rs707922 to tag this LD region for down stream association analyses and characterized the function of this SNP at molecular level. No association between APOM and T2D susceptibility was detected in our Hong Kong Chinese cohort. Interestingly, the C allele of rs805297 was significantly associated with T2D duration of longer than 10 years (OR = 1.245, p = 0.015). The rs707922 TT genotype was significantly associated with elevated plasma total- and LDL- cholesterol levels (p = 0.006 and p = 0.009, respectively) in T2D patients. Molecular analyses of rs707922 lead to the discoveries of a novel transcript APOM5 as well as the cryptic nature of exon 5 of the gene. Ectopic expression of APOM5 transcript confirmed rs707922 allele-dependent activity of the transcript in modifying cholesterol homeostasis in vitro. In conclusion, the results here did not support APOM as a T2D susceptibility gene in Hong Kong Chinese. However, in T2D patients, a subset of APOM SNPs was associated with disease duration and metabolic traits. Further molecular analysis proved the functional activity of rs707922 in APOM expression and in regulation of cellular cholesterol content.",2011 Feb 24,"['Zhou, Jun-Wei', 'Tsui, Stephen K. W.', 'Ng, Maggie C. Y.', 'Geng, Hua', 'Li, Sai-Kam', 'So, Wing-Yee', 'Ma, Ronald C.', 'Wang, Ying', 'Tao, Qian', 'Chen, Zhen-Yu', 'Chan, Juliana C. N.', 'Ho, Yuan-Yuan']",PLoS One,,,False
e09fce29eff5b8f7689858355e94daaa15fe36dc,PMC,Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes,http://dx.doi.org/10.1371/journal.pone.0017324,PMC3044746,21390319,CC BY,"This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. In addition, APOM gene function was further characterized to elucidate its activity in cholesterol metabolism. Seventeen APOM SNPs documented in the NCBI database were genotyped. Five SNPs were confirmed in our study cohort of 1234 T2D and 606 control participants. Three of the five SNPs rs707921(C+1871A), rs707922(G+1837T) and rs805264(G+203A) were in linkage disequilibrium (LD). We chose rs707922 to tag this LD region for down stream association analyses and characterized the function of this SNP at molecular level. No association between APOM and T2D susceptibility was detected in our Hong Kong Chinese cohort. Interestingly, the C allele of rs805297 was significantly associated with T2D duration of longer than 10 years (OR = 1.245, p = 0.015). The rs707922 TT genotype was significantly associated with elevated plasma total- and LDL- cholesterol levels (p = 0.006 and p = 0.009, respectively) in T2D patients. Molecular analyses of rs707922 lead to the discoveries of a novel transcript APOM5 as well as the cryptic nature of exon 5 of the gene. Ectopic expression of APOM5 transcript confirmed rs707922 allele-dependent activity of the transcript in modifying cholesterol homeostasis in vitro. In conclusion, the results here did not support APOM as a T2D susceptibility gene in Hong Kong Chinese. However, in T2D patients, a subset of APOM SNPs was associated with disease duration and metabolic traits. Further molecular analysis proved the functional activity of rs707922 in APOM expression and in regulation of cellular cholesterol content.",2011 Feb 24,"['Zhou, Jun-Wei', 'Tsui, Stephen K. W.', 'Ng, Maggie C. Y.', 'Geng, Hua', 'Li, Sai-Kam', 'So, Wing-Yee', 'Ma, Ronald C.', 'Wang, Ying', 'Tao, Qian', 'Chen, Zhen-Yu', 'Chan, Juliana C. N.', 'Ho, Yuan-Yuan']",PLoS One,,,False
80f7035e6e260377efa2f734629b96d01195d3ea,PMC,Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes,http://dx.doi.org/10.1371/journal.pone.0017324,PMC3044746,21390319,CC BY,"This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. In addition, APOM gene function was further characterized to elucidate its activity in cholesterol metabolism. Seventeen APOM SNPs documented in the NCBI database were genotyped. Five SNPs were confirmed in our study cohort of 1234 T2D and 606 control participants. Three of the five SNPs rs707921(C+1871A), rs707922(G+1837T) and rs805264(G+203A) were in linkage disequilibrium (LD). We chose rs707922 to tag this LD region for down stream association analyses and characterized the function of this SNP at molecular level. No association between APOM and T2D susceptibility was detected in our Hong Kong Chinese cohort. Interestingly, the C allele of rs805297 was significantly associated with T2D duration of longer than 10 years (OR = 1.245, p = 0.015). The rs707922 TT genotype was significantly associated with elevated plasma total- and LDL- cholesterol levels (p = 0.006 and p = 0.009, respectively) in T2D patients. Molecular analyses of rs707922 lead to the discoveries of a novel transcript APOM5 as well as the cryptic nature of exon 5 of the gene. Ectopic expression of APOM5 transcript confirmed rs707922 allele-dependent activity of the transcript in modifying cholesterol homeostasis in vitro. In conclusion, the results here did not support APOM as a T2D susceptibility gene in Hong Kong Chinese. However, in T2D patients, a subset of APOM SNPs was associated with disease duration and metabolic traits. Further molecular analysis proved the functional activity of rs707922 in APOM expression and in regulation of cellular cholesterol content.",2011 Feb 24,"['Zhou, Jun-Wei', 'Tsui, Stephen K. W.', 'Ng, Maggie C. Y.', 'Geng, Hua', 'Li, Sai-Kam', 'So, Wing-Yee', 'Ma, Ronald C.', 'Wang, Ying', 'Tao, Qian', 'Chen, Zhen-Yu', 'Chan, Juliana C. N.', 'Ho, Yuan-Yuan']",PLoS One,,,False
d68205dc527d5f0ee5a9ece74f3e7a7b22af8402,PMC,Dynamically-Driven Inactivation of the Catalytic Machinery of the SARS 3C-Like Protease by the N214A Mutation on the Extra Domain,http://dx.doi.org/10.1371/journal.pcbi.1001084,PMC3044768,21390281,CC BY,"Despite utilizing the same chymotrypsin fold to host the catalytic machinery, coronavirus 3C-like proteases (3CLpro) noticeably differ from picornavirus 3C proteases in acquiring an extra helical domain in evolution. Previously, the extra domain was demonstrated to regulate the catalysis of the SARS-CoV 3CLpro by controlling its dimerization. Here, we studied N214A, another mutant with only a doubled dissociation constant but significantly abolished activity. Unexpectedly, N214A still adopts the dimeric structure almost identical to that of the wild-type (WT) enzyme. Thus, we conducted 30-ns molecular dynamics (MD) simulations for N214A, WT, and R298A which we previously characterized to be a monomer with the collapsed catalytic machinery. Remarkably, three proteases display distinctive dynamical behaviors. While in WT, the catalytic machinery stably retains in the activated state; in R298A it remains largely collapsed in the inactivated state, thus implying that two states are not only structurally very distinguishable but also dynamically well separated. Surprisingly, in N214A the catalytic dyad becomes dynamically unstable and many residues constituting the catalytic machinery jump to sample the conformations highly resembling those of R298A. Therefore, the N214A mutation appears to trigger the dramatic change of the enzyme dynamics in the context of the dimeric form which ultimately inactivates the catalytic machinery. The present MD simulations represent the longest reported so far for the SARS-CoV 3CLpro, unveiling that its catalysis is critically dependent on the dynamics, which can be amazingly modulated by the extra domain. Consequently, mediating the dynamics may offer a potential avenue to inhibit the SARS-CoV 3CLpro.",2011 Feb 24,"['Shi, Jiahai', 'Han, Nanyu', 'Lim, Liangzhong', 'Lua, Shixiong', 'Sivaraman, J.', 'Wang, Lushan', 'Mu, Yuguang', 'Song, Jianxing']",PLoS Comput Biol,,,True
cd33661bfe3aa8e73dc1cd196c34b4eea22d6e4e,PMC,Dynamically-Driven Inactivation of the Catalytic Machinery of the SARS 3C-Like Protease by the N214A Mutation on the Extra Domain,http://dx.doi.org/10.1371/journal.pcbi.1001084,PMC3044768,21390281,CC BY,"Despite utilizing the same chymotrypsin fold to host the catalytic machinery, coronavirus 3C-like proteases (3CLpro) noticeably differ from picornavirus 3C proteases in acquiring an extra helical domain in evolution. Previously, the extra domain was demonstrated to regulate the catalysis of the SARS-CoV 3CLpro by controlling its dimerization. Here, we studied N214A, another mutant with only a doubled dissociation constant but significantly abolished activity. Unexpectedly, N214A still adopts the dimeric structure almost identical to that of the wild-type (WT) enzyme. Thus, we conducted 30-ns molecular dynamics (MD) simulations for N214A, WT, and R298A which we previously characterized to be a monomer with the collapsed catalytic machinery. Remarkably, three proteases display distinctive dynamical behaviors. While in WT, the catalytic machinery stably retains in the activated state; in R298A it remains largely collapsed in the inactivated state, thus implying that two states are not only structurally very distinguishable but also dynamically well separated. Surprisingly, in N214A the catalytic dyad becomes dynamically unstable and many residues constituting the catalytic machinery jump to sample the conformations highly resembling those of R298A. Therefore, the N214A mutation appears to trigger the dramatic change of the enzyme dynamics in the context of the dimeric form which ultimately inactivates the catalytic machinery. The present MD simulations represent the longest reported so far for the SARS-CoV 3CLpro, unveiling that its catalysis is critically dependent on the dynamics, which can be amazingly modulated by the extra domain. Consequently, mediating the dynamics may offer a potential avenue to inhibit the SARS-CoV 3CLpro.",2011 Feb 24,"['Shi, Jiahai', 'Han, Nanyu', 'Lim, Liangzhong', 'Lua, Shixiong', 'Sivaraman, J.', 'Wang, Lushan', 'Mu, Yuguang', 'Song, Jianxing']",PLoS Comput Biol,,,False
da2b409352de17f4c628991dfdf715a08c0d865e,PMC,Dynamically-Driven Inactivation of the Catalytic Machinery of the SARS 3C-Like Protease by the N214A Mutation on the Extra Domain,http://dx.doi.org/10.1371/journal.pcbi.1001084,PMC3044768,21390281,CC BY,"Despite utilizing the same chymotrypsin fold to host the catalytic machinery, coronavirus 3C-like proteases (3CLpro) noticeably differ from picornavirus 3C proteases in acquiring an extra helical domain in evolution. Previously, the extra domain was demonstrated to regulate the catalysis of the SARS-CoV 3CLpro by controlling its dimerization. Here, we studied N214A, another mutant with only a doubled dissociation constant but significantly abolished activity. Unexpectedly, N214A still adopts the dimeric structure almost identical to that of the wild-type (WT) enzyme. Thus, we conducted 30-ns molecular dynamics (MD) simulations for N214A, WT, and R298A which we previously characterized to be a monomer with the collapsed catalytic machinery. Remarkably, three proteases display distinctive dynamical behaviors. While in WT, the catalytic machinery stably retains in the activated state; in R298A it remains largely collapsed in the inactivated state, thus implying that two states are not only structurally very distinguishable but also dynamically well separated. Surprisingly, in N214A the catalytic dyad becomes dynamically unstable and many residues constituting the catalytic machinery jump to sample the conformations highly resembling those of R298A. Therefore, the N214A mutation appears to trigger the dramatic change of the enzyme dynamics in the context of the dimeric form which ultimately inactivates the catalytic machinery. The present MD simulations represent the longest reported so far for the SARS-CoV 3CLpro, unveiling that its catalysis is critically dependent on the dynamics, which can be amazingly modulated by the extra domain. Consequently, mediating the dynamics may offer a potential avenue to inhibit the SARS-CoV 3CLpro.",2011 Feb 24,"['Shi, Jiahai', 'Han, Nanyu', 'Lim, Liangzhong', 'Lua, Shixiong', 'Sivaraman, J.', 'Wang, Lushan', 'Mu, Yuguang', 'Song, Jianxing']",PLoS Comput Biol,,,False
5303b7430b20a5e665f7cadd07ae77baa5687e73,PMC,Statistical learning techniques applied to epidemiology: a simulated case-control comparison study with logistic regression,http://dx.doi.org/10.1186/1471-2105-12-37,PMC3045299,21272346,CC BY,"BACKGROUND: When investigating covariate interactions and group associations with standard regression analyses, the relationship between the response variable and exposure may be difficult to characterize. When the relationship is nonlinear, linear modeling techniques do not capture the nonlinear information content. Statistical learning (SL) techniques with kernels are capable of addressing nonlinear problems without making parametric assumptions. However, these techniques do not produce findings relevant for epidemiologic interpretations. A simulated case-control study was used to contrast the information embedding characteristics and separation boundaries produced by a specific SL technique with logistic regression (LR) modeling representing a parametric approach. The SL technique was comprised of a kernel mapping in combination with a perceptron neural network. Because the LR model has an important epidemiologic interpretation, the SL method was modified to produce the analogous interpretation and generate odds ratios for comparison. RESULTS: The SL approach is capable of generating odds ratios for main effects and risk factor interactions that better capture nonlinear relationships between exposure variables and outcome in comparison with LR. CONCLUSIONS: The integration of SL methods in epidemiology may improve both the understanding and interpretation of complex exposure/disease relationships.",2011 Jan 27,"['Heine, John J', 'Land, Walker H', 'Egan, Kathleen M']",BMC Bioinformatics,,,True
4c45bdd7e23c8ea6b0dfb04d48a5ceda8f022597,PMC,Non-Invasive Microstructure and Morphology Investigation of the Mouse Lung: Qualitative Description and Quantitative Measurement,http://dx.doi.org/10.1371/journal.pone.0017400,PMC3045447,21364899,CC BY,"BACKGROUND: Early detection of lung cancer is known to improve the chances of successful treatment. However, lungs are soft tissues with complex three-dimensional configuration. Conventional X-ray imaging is based purely on absorption resulting in very low contrast when imaging soft tissues without contrast agents. It is difficult to obtain adequate information of lung lesions from conventional X-ray imaging. METHODS: In this study, a recently emerged imaging technique, in-line X-ray phase contrast imaging (IL-XPCI) was used. This powerful technique enabled high-resolution investigations of soft tissues without contrast agents. We applied IL-XPCI to observe the lungs in an intact mouse for the purpose of defining quantitatively the micro-structures in lung. FINDINGS: The three-dimensional model of the lung was successfully established, which provided an excellent view of lung airways. We highlighted the use of IL-XPCI in the visualization and assessment of alveoli which had rarely been studied in three dimensions (3D). The precise view of individual alveolus was achieved. The morphological parameters, such as diameter and alveolar surface area were measured. These parameters were of great importance in the diagnosis of diseases related to alveolus and alveolar scar. CONCLUSION: Our results indicated that IL-XPCI had the ability to represent complex anatomical structures in lung. This offered a new perspective on the diagnosis of respiratory disease and may guide future work in the study of respiratory mechanism on the alveoli level.",2011 Feb 25,"['Zhang, Lu', 'Li, Dongyue', 'Luo, Shuqian']",PLoS One,,,True
bafbd40e253b24fc6b10b66bf68fe838e0a6a313,PMC,Variability and Diversity of Nasopharyngeal Microbiota in Children: A Metagenomic Analysis,http://dx.doi.org/10.1371/journal.pone.0017035,PMC3046172,21386965,CC BY,"The nasopharynx is the ecological niche for many commensal bacteria and for potential respiratory or invasive pathogens like Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. Disturbance of a balanced nasopharyngeal (NP) microbiome might be involved in the onset of symptomatic infections with these pathogens, which occurs primarily in fall and winter. It is unknown whether seasonal infection patterns are associated with concomitant changes in NP microbiota. As young children are generally prone to respiratory and invasive infections, we characterized the NP microbiota of 96 healthy children by barcoded pyrosequencing of the V5–V6 hypervariable region of the 16S-rRNA gene, and compared microbiota composition between children sampled in winter/fall with children sampled in spring. The approximately 1000000 sequences generated represented 13 taxonomic phyla and approximately 250 species-level phyla types (OTUs). The 5 most predominant phyla were Proteobacteria (64%), Firmicutes (21%), Bacteroidetes (11%), Actinobacteria (3%) and Fusobacteria (1,4%) with Moraxella, Haemophilus, Streptococcus, Flavobacteria, Dolosigranulum, Corynebacterium and Neisseria as predominant genera. The inter-individual variability was that high that on OTU level a core microbiome could not be defined. Microbiota profiles varied strongly with season, with in fall/winter a predominance of Proteobacteria (relative abundance (% of all sequences): 75% versus 51% in spring) and Fusobacteria (absolute abundance (% of children): 14% versus 2% in spring), and in spring a predominance of Bacteroidetes (relative abundance: 19% versus 3% in fall/winter, absolute abundance: 91% versus 54% in fall/winter), and Firmicutes. The latter increase is mainly due to (Brevi)bacillus and Lactobacillus species (absolute abundance: 96% versus 10% in fall/winter) which are like Bacteroidetes species generally related to healthy ecosystems. The observed seasonal effects could not be attributed to recent antibiotics or viral co-infection. The NP microbiota of young children is highly diverse and appears different between seasons. These differences seem independent of antibiotic use or viral co-infection.",2011 Feb 28,"['Bogaert, Debby', 'Keijser, Bart', 'Huse, Susan', 'Rossen, John', 'Veenhoven, Reinier', 'van Gils, Elske', 'Bruin, Jacob', 'Montijn, Roy', 'Bonten, Marc', 'Sanders, Elisabeth']",PLoS One,,,True
5cd3d3edd1b68bce986c6b9e6bfa9720efd041e3,PMC,A rebuttal to the comments on the genome order index and the Z-curve,http://dx.doi.org/10.1186/1745-6150-6-10,PMC3046898,21324187,CC BY,"BACKGROUND: Elhaik, Graur and Josic recently commented on the genome order index (S) and the Z-curve (Elhaik et al. Biol Direct 2010, 5: 10). S is a quantity defined as S = a(2 )+ c(2 )+ g(2 )+ t(2), where a, c, g and t denote corresponding base frequencies. The Z-curve is a three dimensional curve that represents a DNA sequence in the manner that each can be uniquely reconstructed given the other. Elhaik et al. made 4 major claims. 1) In the previous mapping system with the regular tetrahedron, calculation of the radius of the inscribed sphere is ""a mathematical error"". 2) S follows an exponential distribution and is narrowly distributed with a range of (0.25 - 0.33). 3) Based on the Chargaff's second parity rule (PR2), ""S is equivalent to H [Shannon entropy]"" and they are derivable from each other. 4) Z-curve ""suffers from over dimensionality"", because based on the analysis of 235 bacterial genomes, x and y components contributed only less than 1% of the variance and therefore ""would be of little use"". RESULTS: 1) Elhaik et al. mistakenly neglected the parameter [Formula: see text] when calculating the radius of the inscribed sphere. 2) The exponential distribution of S is a restatement of our previous conclusion, and the range of (0.25 - 0.33) only paraphrases the previously suggested S range (0.25 -1/3). 3) Elhaik et al. incorrectly disregard deviations from PR2 by treating the deviations as 0 altogether, reduce S and H, both having 4 variables, a, c, g and t, into functions of one single variable, a only, and apply this treatment to all DNA sequences as the basis of their ""demonstration"", which is therefore invalid. 4) Elhaik et al. confuse numeral smallness with biological insignificance, and disregard the distributions of purine/pyrimidine and amino/keto bases (x and y components), the variations of which, although can be less than that of GC content, contain rich information that is important and useful, such as in locating replication origins of bacterial and archaeal genomes, and in studies of gene recognition in various species. CONCLUSION: Elhaik et al. confuse S (a single number) with Z-curve (a series of 3D coordinates), which are distinct. To use S as a case study of Z-curve, by itself, is invalid. S and H are neither equivalent nor derivable from each other. The criticisms of Elhaik, Graur and Josic are wrong. REVIEWERS: This article was reviewed by Erik van Nimwegen.",2011 Feb 16,"Zhang, Ren",Biol Direct,,,True
e42218bb9ddb954382e0db792ffeae988bf62545,PMC,"Large-scale seroprevalence analysis of human metapneumovirus and human respiratory syncytial virus infections in Beijing, China",http://dx.doi.org/10.1186/1743-422X-8-62,PMC3046927,21310026,CC BY,"BACKGROUND: Human metapneumovirus (hMPV), a recently identified virus, causes acute respiratory tract infections (ARTIs) in infants and children. However, studies on the seroepidemeology of hMPV are very limited in China. To assess the seroprevalence of hMPV infection in China, we tested a total of 1,156 serum specimens for the presence of anti-hMPV IgG antibody in children and adults free of acute respiratory illness in Beijing, China by using hMPV nucleocapsid (N) protein as an antigen. As a control, we used the human serum antibody against the N protein of human respiratory syncytial virus (hRSV), the most important viral agent responsible for ARIs in children. RESULTS: The seropositive rate for hMPV increased steadily with age from 67% at 1-6 mo to 100% at age 20. However, the rate dropped slightly between 6 mo and 1 yr of age. The seropositive rate for hRSV also increased steadily with age from 71% at 1-6 mo to 100% at age 20. In children aged six months to six years, the seropositive rates for the anti-hRSV IgG antibody were significantly higher than those for hMPV. Additionally, IgG antibody titers to hMPV and hRSV were significantly higher in adults than in young children. Consistent with the seropositive rates, the geometric mean titer of anti-hMPV IgG antibody was lower than that of anti-hRSV IgG antibody in children aged six months to six years. CONCLUSIONS: Our results indicate that similar to hRSV, exposure to hMPV is ubiquitous in the Beijing population. However, the seroprevalence of anti-hMPV IgG antibody is lower than that of hRSV in children between six months and six years old, which suggests a different number of repeat infections or a different response to infections.",2011 Feb 10,"['Lu, Guilan', 'Gonzalez, Richard', 'Guo, Li', 'Wu, Chao', 'Wu, Jiang', 'Vernet, Guy', 'Paranhos-Baccalà, Gláucia', 'Wang, Jianwei', 'Hung, Tao']",Virol J,,,True
79979652a864cef3a41342ccb1add48e5ad0cf85,PMC,Plant Plastid Engineering,http://dx.doi.org/10.2174/138920210793175912,PMC3048312,21532834,CC BY,"Genetic material in plants is distributed into nucleus, plastids and mitochondria. Plastid has a central role of carrying out photosynthesis in plant cells. Plastid transformation is becoming more popular and an alternative to nuclear gene transformation because of various advantages like high protein levels, the feasibility of expressing multiple proteins from polycistronic mRNAs, and gene containment through the lack of pollen transmission. Recently, much progress in plastid engineering has been made. In addition to model plant tobacco, many transplastomic crop plants have been generated which possess higher resistance to biotic and abiotic stresses and molecular pharming. In this mini review, we will discuss the features of the plastid DNA and advantages of plastid transformation. We will also present some examples of transplastomic plants developed so far through plastid engineering, and the various applications of plastid transformation.",2010 Nov,"['Wani, Shabir H.', 'Haider, Nadia', 'Kumar, Hitesh', 'Singh, N.B.']",Curr Genomics,,,True
258b69aa1d0bb32cf913f8124f8c053442522f6b,PMC,"Viral Etiology of Influenza-Like Illnesses in Antananarivo, Madagascar, July 2008 to June 2009",http://dx.doi.org/10.1371/journal.pone.0017579,PMC3048401,21390235,CC BY,"BACKGROUND: In Madagascar, despite an influenza surveillance established since 1978, little is known about the etiology and prevalence of viruses other than influenza causing influenza-like illnesses (ILIs). METHODOLOGY/PRINCIPAL FINDINGS: From July 2008 to June 2009, we collected respiratory specimens from patients who presented ILIs symptoms in public and private clinics in Antananarivo (the capital city of Madagascar). ILIs were defined as body temperature ≥38°C and cough and at least two of the following symptoms: sore throat, rhinorrhea, headache and muscular pain, for a maximum duration of 3 days. We screened these specimens using five multiplex real time Reverse Transcription and/or Polymerase Chain Reaction assays for detection of 14 respiratory viruses. We detected respiratory viruses in 235/313 (75.1%) samples. Overall influenza virus A (27.3%) was the most common virus followed by rhinovirus (24.8%), RSV (21.2%), adenovirus (6.1%), coronavirus OC43 (6.1%), influenza virus B (3.9%), parainfluenza virus-3 (2.9%), and parainfluenza virus-1 (2.3%). Co-infections occurred in 29.4% (69/235) of infected patients and rhinovirus was the most detected virus (27.5%). Children under 5 years were more likely to have one or more detectable virus associated with their ILI. In this age group, compared to those ≥5 years, the risk of detecting more than one virus was higher (OR = 1.9), as was the risk of detecting of RSV (OR = 10.1) and adenovirus (OR = 4.7). While rhinovirus and adenovirus infections occurred year round, RSV, influenza virus A and coronavirus OC43 had defined period of circulation. CONCLUSIONS: In our study, we found that respiratory viruses play an important role in ILIs in the Malagasy community, particularly in children under 5 years old. These data provide a better understanding of the viral etiology of outpatients with ILI and describe for the first time importance of these viruses in different age group and their period of circulation.",2011 Mar 3,"['Razanajatovo, Norosoa Harline', 'Richard, Vincent', 'Hoffmann, Jonathan', 'Reynes, Jean-Marc', 'Razafitrimo, Girard Marcellin', 'Randremanana, Rindra Vatosoa', 'Heraud, Jean-Michel']",PLoS One,,,True
a040109f4ae97738c7940d711a60f07f573b9754,PMC,H9N2 influenza virus acquires intravenous pathogenicity on the introduction of a pair of di-basic amino acid residues at the cleavage site of the hemagglutinin and consecutive passages in chickens,http://dx.doi.org/10.1186/1743-422X-8-64,PMC3048564,21310053,CC BY,"BACKGROUND: Outbreaks of avian influenza (AI) caused by infection with low pathogenic H9N2 viruses have occurred in poultry, resulting in serious economic losses in Asia and the Middle East. It has been difficult to eradicate the H9N2 virus because of its low pathogenicity, frequently causing in apparent infection. It is important for the control of AI to assess whether the H9N2 virus acquires pathogenicity as H5 and H7 viruses. In the present study, we investigated whether a non-pathogenic H9N2 virus, A/chicken/Yokohama/aq-55/2001 (Y55) (H9N2), acquires pathogenicity in chickens when a pair of di-basic amino acid residues is introduced at the cleavage site of its HA molecule. RESULTS: rgY55sub (H9N2), which had four basic amino acid residues at the HA cleavage site, replicated in MDCK cells in the absence of trypsin after six consecutive passages in the air sacs of chicks, and acquired intravenous pathogenicity to chicken after four additional passages. More than 75% of chickens inoculated intravenously with the passaged virus, rgY55sub-P10 (H9N2), died, indicating that it is pathogenic comparable to that of highly pathogenic avian influenza viruses (HPAIVs) defined by World Organization for Animal Health (OIE). The chickens inoculated with the virus via the intranasal route, however, survived without showing any clinical signs. On the other hand, an avirulent H5N1 strain, A/duck/Hokkaido/Vac-1/2004 (Vac1) (H5N1), acquired intranasal pathogenicity after a pair of di-basic amino acid residues was introduced into the cleavage site of the HA, followed by two passages by air sac inoculation in chicks. CONCLUSION: The present results demonstrate that an H9N2 virus has the potential to acquire intravenous pathogenicity in chickens although the morbidity via the nasal route of infection is lower than that of H5N1 HPAIV.",2011 Feb 10,"['Soda, Kosuke', 'Asakura, Shingo', 'Okamatsu, Masatoshi', 'Sakoda, Yoshihiro', 'kida, Hiroshi']",Virol J,,,True
cdb117ad4ac490f1e48e3738d5ccdaafe8916086,PMC,"A multicentre, randomised, double-blind, single-dose study assessing the efficacy of AMC/DCBA Warm lozenge or AMC/DCBA Cool lozenge in the relief of acute sore throat",http://dx.doi.org/10.1186/1471-2296-12-6,PMC3050701,21332976,CC BY,"BACKGROUND: Clinically proven over-the-counter (OTC) treatment options are becoming increasingly important in the self-management of acute sore throat. The aim of this study was to determine the analgesic and sensorial benefits of two different amylmetacresol/2,4-dichlorobenzyl alcohol (AMC/DCBA) throat lozenge formulation variants, AMC/DCBA Warm lozenge and AMC/DCBA Cool lozenge, compared with an unflavoured, non-medicated placebo lozenge in the relief of acute sore throat due to upper respiratory tract infections. METHODS: In this multicentre, randomised, double-blind, single-dose study, 225 adult patients with acute sore throat were randomly assigned to receive either one AMC/DCBA Warm lozenge (n = 77), one AMC/DCBA Cool lozenge (n = 74) or one unflavoured, non-medicated lozenge (matched for size, shape and demulcency; n = 74). After baseline assessments, patients received their assigned lozenge and completed four rating assessments at 11 timepoints from 1 to 120 minutes post dose. Analgesic properties were assessed by comparing severity of throat soreness and sore throat relief ratings. Difficulty in swallowing, throat numbness, functional, sensorial and emotional benefits were also assessed. RESULTS: Both the AMC/DCBA Warm and AMC/DCBA Cool lozenge induced significant analgesic, functional, sensorial and emotional effects compared with the unflavoured, non-medicated lozenge. Sore throat relief, improvements in throat soreness and difficulty in swallowing, and throat numbness were observed as early as 1-5 minutes, and lasted up to 2 hours post dose. Sensorial benefits of warming and cooling associated with the AMC/DCBA Warm and AMC/DCBA Cool lozenge, respectively, were experienced soon after first dose, and in the case of the latter, it lasted long after the lozenge had dissolved. Emotional benefits of feeling better, happier, less distracted and less frustrated were reported in those taking either of the AMC/DCBA throat lozenge variants, with no differences in adverse events compared with the unflavoured, non-medicated lozenge. CONCLUSIONS: AMC/DCBA Warm and AMC/DCBA Cool lozenges are well-tolerated and effective OTC treatment options, offering functional, sensorial and emotional benefits to patients with acute sore throat, over and above that of the rapid efficacy effects provided. TRIAL REGISTRATION: ISRCTN: ISRCTN00003567",2011 Feb 18,"['Wade, Alan G', 'Morris, Christopher', 'Shephard, Adrian', 'Crawford, Gordon M', 'Goulder, Michael A']",BMC Fam Pract,,,True
7d92312dac3822da87cb86d3de9fe818e0ee2874,PMC,Peptide inhibition of human cytomegalovirus infection,http://dx.doi.org/10.1186/1743-422X-8-76,PMC3050824,21342525,CC BY,"BACKGROUND: Human cytomegalovirus (HCMV) is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV)- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB), a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. RESULTS: Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS), several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF) were infected with the Towne-GFP strain of HCMV (0.5 MOI), preincubated with peptides at a range of concentrations (78 nm to 100 μM), and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100 μM and 50 μM, respectively, and 60% at a concentration of 2.5 μM. While peptides 264-291 and 297-315, individually failed to inhibit viral infection, when combined, they showed 67% inhibition of HCMV infection at a concentration of 0.125 μM each. CONCLUSIONS: Peptides designed to target putative fusogenic domains of gB provide a basis for the development of novel therapeutics that prevent HCMV infection.",2011 Feb 22,"['Melnik, Lilia I', 'Garry, Robert F', 'Morris, Cindy A']",Virol J,,,True
985a0071613514c5f07592dc4d94d8916c2052d0,PMC,Risk Factors of Streptococcus suis Infection in Vietnam. A Case-Control Study,http://dx.doi.org/10.1371/journal.pone.0017604,PMC3050921,21408132,CC BY,"BACKGROUND: Streptococcus suis infection, an emerging zoonosis, is an increasing public health problem across South East Asia and the most common cause of acute bacterial meningitis in adults in Vietnam. Little is known of the risk factors underlying the disease. METHODS AND FINDINGS: A case-control study with appropriate hospital and matched community controls for each patient was conducted between May 2006 and June 2009. Potential risk factors were assessed using a standardized questionnaire and investigation of throat and rectal S. suis carriage in cases, controls and their pigs, using real-time PCR and culture of swab samples. We recruited 101 cases of S. suis meningitis, 303 hospital controls and 300 community controls. By multivariate analysis, risk factors identified for S. suis infection as compared to either control group included eating “high risk” dishes, including such dishes as undercooked pig blood and pig intestine (OR(1) = 2.22; 95%CI = [1.15–4.28] and OR(2) = 4.44; 95%CI = [2.15–9.15]), occupations related to pigs (OR(1) = 3.84; 95%CI = [1.32–11.11] and OR(2) = 5.52; 95%CI = [1.49–20.39]), and exposures to pigs or pork in the presence of skin injuries (OR(1) = 7.48; 95%CI = [1.97–28.44] and OR(2) = 15.96; 95%CI = [2.97–85.72]). S. suis specific DNA was detected in rectal and throat swabs of 6 patients and was cultured from 2 rectal samples, but was not detected in such samples of 1522 healthy individuals or patients without S. suis infection. CONCLUSIONS: This case control study, the largest prospective epidemiological assessment of this disease, has identified the most important risk factors associated with S. suis bacterial meningitis to be eating ‘high risk’ dishes popular in parts of Asia, occupational exposure to pigs and pig products, and preparation of pork in the presence of skin lesions. These risk factors can be addressed in public health campaigns aimed at preventing S. suis infection.",2011 Mar 8,"['Ho, Dang Trung Nghia', 'Le, Thi Phuong Tu', 'Wolbers, Marcel', 'Cao, Quang Thai', 'Nguyen, Van Minh Hoang', 'Tran, Vu Thieu Nga', 'Le, Thi Phuong Thao', 'Nguyen, Hoan Phu', 'Tran, Thi Hong Chau', 'Dinh, Xuan Sinh', 'To, Song Diep', 'Hoang, Thi Thanh Hang', 'Hoang, Truong', 'Campbell, James', 'Nguyen, Van Vinh Chau', 'Nguyen, Tran Chinh', 'Nguyen, Van Dung', 'Ngo, Thi Hoa', 'Spratt, Brian G.', 'Tran, Tinh Hien', 'Farrar, Jeremy', 'Schultsz, Constance']",PLoS One,,,True
1686765b6847c2b132d0129be10f7263bac5973e,PMC,Experimental infection of hamsters with avian paramyxovirus serotypes 1 to 9,http://dx.doi.org/10.1186/1297-9716-42-38,PMC3052182,21345199,CC BY,"Avian paramyxoviruses (APMVs) are frequently isolated from domestic and wild birds throughout the world and are separated into nine serotypes (APMV-1 to -9). Only in the case of APMV-1, the infection of non-avian species has been investigated. The APMVs presently are being considered as human vaccine vectors. In this study, we evaluated the replication and pathogenicity of all nine APMV serotypes in hamsters. The hamsters were inoculated intranasally with each virus and monitored for clinical disease, pathology, histopathology, virus replication, and seroconversion. On the basis of one or more of these criteria, each of the APMV serotypes was found to replicate in hamsters. The APMVs produced mild or inapparent clinical signs in hamsters except for APMV-9, which produced moderate disease. Gross lesions were observed over the pulmonary surface of hamsters infected with APMV-2 & -3, which showed petechial and ecchymotic hemorrhages, respectively. Replication of all of the APMVs except APMV-5 was confirmed in the nasal turbinates and lungs, indicating a tropism for the respiratory tract. Histologically, the infection resulted in lung lesions consistent with bronchointerstitial pneumonia of varying severity and nasal turbinates with blunting or loss of cilia of the epithelium lining the nasal septa. The majority of APMV-infected hamsters exhibited transient histological lesions that self resolved by 14 days post infection (dpi). All of the hamsters infected with the APMVs produced serotype-specific HI or neutralizing antibodies, confirming virus replication. Taken together, these results demonstrate that all nine known APMV serotypes are capable of replicating in hamsters with minimal disease and pathology.",2011 Feb 23,"['Samuel, Arthur S', 'Subbiah, Madhuri', 'Shive, Heather', 'Collins, Peter L', 'Samal, Siba K']",Vet Res,,,True
ae40184ce67c93d60f2d5d00f451b00017af16cb,PMC,Estimation of transmission parameters of a fluoroquinolone-resistant Escherichia coli strain between pigs in experimental conditions,http://dx.doi.org/10.1186/1297-9716-42-44,PMC3053234,21366902,CC BY,"Antimicrobial resistance is of primary importance regarding public and animal health issues. Persistence and spread of resistant strains within a population contribute to the maintenance of a reservoir and lead to treatment failure. An experimental trial was carried out to study the horizontal transmission of a fluoroquinolone-resistant Escherichia coli strain from inoculated to naïve pigs. All naïve contact pigs had positive counts of fluoroquinolone-resistant E. coli after only two days of contact. Moreover, re-infections of inoculated pigs caused by newly contaminated animals were suspected. A maximum likelihood method, based on a susceptible-infectious-susceptible (SIS) model, was used to determine the transmission parameters. Two transmission levels were identified depending on the quantity of bacteria shed by infected individuals: (i) low-shedders with bacterial counts of resistant E. coli in the faeces between 5*10(3 )and 10(6 )CFU/g (β(L )= 0.41 [0.27; 0.62]), (ii) high shedders with bacterial counts above 10(6 )CFU/g (β(H )= 0.98 [0.59; 1.62]). Hence, transmission between animals could be pivotal in explaining the persistence of resistant bacteria within pig herds.",2011 Mar 2,"['Andraud, Mathieu', 'Rose, Nicolas', 'Laurentie, Michel', 'Sanders, Pascal', 'Le Roux, Aurélie', 'Cariolet, Roland', 'Chauvin, Claire', 'Jouy, Eric']",Vet Res,,,True
9791652bce8752738f1bfb75305fd5faa6e30374,PMC,Factors Affecting Intention to Receive and Self-Reported Receipt of 2009 Pandemic (H1N1) Vaccine in Hong Kong: A Longitudinal Study,http://dx.doi.org/10.1371/journal.pone.0017713,PMC3055876,21412418,CC BY,"BACKGROUND: Vaccination was a core component for mitigating the 2009 influenza pandemic (pH1N1). However, a vaccination program's efficacy largely depends on population compliance. We examined general population decision-making for pH1N1 vaccination using a modified Theory of Planned Behaviour (TBP). METHODOLOGY: We conducted a longitudinal study, collecting data before and after the introduction of pH1N1 vaccine in Hong Kong. Structural equation modeling (SEM) tested if a modified TPB had explanatory utility for vaccine uptake among adults. PRINCIPAL FINDINGS: Among 896 subjects who completed both the baseline and the follow-up surveys, 7% (67/896) reported being “likely/very likely/certain” to be vaccinated (intent) but two months later only 0.8% (7/896) reported having received pH1N1 vaccination. Perception of low risk from pH1N1 (60%) and concerns regarding adverse effects of the vaccine (37%) were primary justifications for avoiding pH1N1 vaccination. Greater perceived vaccine benefits (β = 0.15), less concerns regarding vaccine side-effects (β = −0.20), greater adherence to social norms of vaccination (β = 0.39), anticipated higher regret if not vaccinated (β = 0.47), perceived higher self-efficacy for vaccination (β = 0.12) and history of seasonal influenza vaccination (β = 0.12) were associated with higher intention to receive the pH1N1 vaccine, which in turn predicted self-reported vaccination uptake (β = 0.30). Social norm (β = 0.70), anticipated regret (β = 0.19) and vaccination intention (β = 0.31) were positively associated with, and accounted for 70% of variance in vaccination planning, which, in turn subsequently predicted self-reported vaccination uptake (β = 0.36) accounting for 36% of variance in reported vaccination behaviour. CONCLUSIONS/SIGNIFICANCE: Perceived low risk from pH1N1 and perceived high risk from pH1N1 vaccine inhibited pH1N1 vaccine uptake. Both the TPB and the additional components contributed to intended vaccination uptake but social norms and anticipated regret predominantly associated with vaccination intention and planning. Vaccination planning is a more significant proximal determinant of uptake of pH1N1 vaccine than is intention. Intention alone is an unreliable predictor of future vaccine uptake.",2011 Mar 11,"['Liao, Qiuyan', 'Cowling, Benjamin J.', 'Lam, Wendy Wing Tak', 'Fielding, Richard']",PLoS One,,,True
c24af6314214e7d2ef8b04419efccd6f7f900858,PMC,Epithelial Cell Stretching and Luminal Acidification Lead to a Retarded Development of Stria Vascularis and Deafness in Mice Lacking Pendrin,http://dx.doi.org/10.1371/journal.pone.0017949,PMC3056798,21423764,CC BY,"Loss-of-function mutations of SLC26A4/pendrin are among the most prevalent causes of deafness. Deafness and vestibular dysfunction in the corresponding mouse model, Slc26a4(−/−), are associated with an enlargement and acidification of the membranous labyrinth. Here we relate the onset of expression of the HCO(3) (−) transporter pendrin to the luminal pH and to enlargement-associated epithelial cell stretching. We determined expression with immunocytochemistry, cell stretching by digital morphometry and pH with double-barreled ion-selective electrodes. Pendrin was first expressed in the endolymphatic sac at embryonic day (E) 11.5, in the cochlear hook-region at E13.5, in the utricle and saccule at E14.5, in ampullae at E16.5, and in the upper turn of the cochlea at E17.5. Epithelial cell stretching in Slc26a4(−/−) mice began at E14.5. pH changes occurred first in the cochlea at E15.5 and in the endolymphatic sac at E17.5. At postnatal day 2, stria vascularis, outer sulcus and Reissner's membrane epithelial cells, and utricular and saccular transitional cells were stretched, whereas sensory cells in the cochlea, utricle and saccule did not differ between Slc26a4(+/−) and Slc26a4(−/−) mice. Structural development of stria vascularis, including vascularization, was retarded in Slc26a4(−/−) mice. In conclusion, the data demonstrate that the enlargement and stretching of non-sensory epithelial cells precedes luminal acidification in the cochlea and the endolymphatic sac. Stretching and luminal acidification may alter cell-to-cell communication and lead to the observed retarded development of stria vascularis, which may be an important step on the path to deafness in Slc26a4(−/−) mice, and possibly in humans, lacking functional pendrin expression.",2011 Mar 14,"['Kim, Hyoung-Mi', 'Wangemann, Philine']",PLoS One,,,True
bb3716d66667c66f6f79b37c765388cd334f2cad,PMC,Tylosema esculentum (Marama) Tuber and Bean Extracts Are Strong Antiviral Agents against Rotavirus Infection,http://dx.doi.org/10.1155/2011/284795,PMC3057194,21423688,CC BY,"Tylosema esculentum (marama) beans and tubers are used as food, and traditional medicine against diarrhoea in Southern Africa. Rotaviruses (RVs) are a major cause of diarrhoea among infants, young children, immunocompromised people, and domesticated animals. Our work is first to determine anti-RV activity of marama bean and tuber ethanol and water extracts; in this case on intestinal enterocyte cells of human infant (H4), adult pig (CLAB) and adult bovine (CIEB) origin. Marama cotyledon ethanolic extract (MCE) and cotyledon water extract (MCW) without RV were not cytotoxic to all cells tested, while seed coat and tuber extracts showed variable levels of cytotoxicity. Marama cotyledon ethanolic and water extracts (MCE and MCW, resp.) (≥0.1 mg/mL), seed coat extract (MSCE) and seed coat water extract (MSCW) (0.01 to 0.001 mg/mL), especially ethanolic, significantly increased cell survival and enhanced survival to cytopathic effects of RV by at least 100% after in vitro co- and pre-incubation treatments. All marama extracts used significantly enhanced nitric oxide release from H4 cells and enhanced TER (Ω/cm(2)) of enterocyte barriers after coincubation with RV. Marama cotyledon and seed coat extracts inhibited virion infectivity possibly through interference with replication due to accumulation of nitric oxide. Marama extracts are therefore promising microbicides against RV.",2011 Feb 20,"['Chingwaru, Walter', 'Majinda, Runner T.', 'Yeboah, Sam O.', 'Jackson, Jose C.', 'Kapewangolo, Petrina T.', 'Kandawa-Schulz, Martha', 'Cencic, Avrelija']",Evid Based Complement Alternat Med,,,True
f3b46e7e8f58799207cc44515f859c1daf5e4dfc,PMC,Exhaled breath condensate sampling is not a new method for detection of respiratory viruses,http://dx.doi.org/10.1186/1743-422X-8-98,PMC3059288,21375748,CC BY,"BACKGROUND: Exhaled breath condensate (EBC) sampling has been considered an inventive and novel method for the isolation of respiratory viruses. METHODS: In our study, 102 volunteers experiencing upper airway infection were recruited over the winter and early spring of 2008/2009 and the first half of the winter of 2009/2010. Ninety-nine EBCs were successfully obtained and screened for 14 commonly circulating respiratory viruses. To investigate the efficiency of virus isolation from EBC, a nasal swab was taken in parallel from a subset of volunteers. The combined use of the ECoVent device with the RTube™ allowed the registration of the exhaled volume and breathing frequency during collection. In this way, the number of exhaled viral particles per liter air or per minute can theoretically be estimated. RESULTS: Viral screening resulted in the detection of 4 different viruses in EBC and/or nasal swabs: Rhinovirus, Human Respiratory Syncytial Virus B, Influenza A and Influenza B. Rhinovirus was detected in 6 EBCs and 1 EBC was Influenza B positive. We report a viral detection rate of 7% for the EBCs, which is much lower than the detection rate of 46.8% observed using nasal swabs. CONCLUSION: Although very promising, EBC collection using the RTube™ is not reliable for diagnosis of respiratory infections.",2011 Mar 4,"['Houspie, Lieselot', 'De Coster, Sarah', 'Keyaerts, Els', 'Narongsack, Phouthalack', 'De Roy, Rikka', 'Talboom, Ive', 'Sisk, Maura', 'Maes, Piet', 'Verbeeck, Jannick', 'Van Ranst, Marc']",Virol J,,,True
c44a9d064faca56bd284971828e4db13e656365c,PMC,Autonomous Targeting of Infectious Superspreaders Using Engineered Transmissible Therapies,http://dx.doi.org/10.1371/journal.pcbi.1002015,PMC3060167,21483468,CC BY,"Infectious disease treatments, both pharmaceutical and vaccine, face three universal challenges: the difficulty of targeting treatments to high-risk ‘superspreader’ populations who drive the great majority of disease spread, behavioral barriers in the host population (such as poor compliance and risk disinhibition), and the evolution of pathogen resistance. Here, we describe a proposed intervention that would overcome these challenges by capitalizing upon Therapeutic Interfering Particles (TIPs) that are engineered to replicate conditionally in the presence of the pathogen and spread between individuals — analogous to ‘transmissible immunization’ that occurs with live-attenuated vaccines (but without the potential for reversion to virulence). Building on analyses of HIV field data from sub-Saharan Africa, we construct a multi-scale model, beginning at the single-cell level, to predict the effect of TIPs on individual patient viral loads and ultimately population-level disease prevalence. Our results show that a TIP, engineered with properties based on a recent HIV gene-therapy trial, could stably lower HIV/AIDS prevalence by ∼30-fold within 50 years and could complement current therapies. In contrast, optimistic antiretroviral therapy or vaccination campaigns alone could only lower HIV/AIDS prevalence by <2-fold over 50 years. The TIP's efficacy arises from its exploitation of the same risk factors as the pathogen, allowing it to autonomously penetrate superspreader populations, maintain efficacy despite behavioral disinhibition, and limit viral resistance. While demonstrated here for HIV, the TIP concept could apply broadly to many viral infectious diseases and would represent a new paradigm for disease control, away from pathogen eradication but toward robust disease suppression.",2011 Mar 17,"['Metzger, Vincent T.', 'Lloyd-Smith, James O.', 'Weinberger, Leor S.']",PLoS Comput Biol,,,True
40400327bbd828910ba0e013d9de71c012b4d4e1,PMC,Autonomous Targeting of Infectious Superspreaders Using Engineered Transmissible Therapies,http://dx.doi.org/10.1371/journal.pcbi.1002015,PMC3060167,21483468,CC BY,"Infectious disease treatments, both pharmaceutical and vaccine, face three universal challenges: the difficulty of targeting treatments to high-risk ‘superspreader’ populations who drive the great majority of disease spread, behavioral barriers in the host population (such as poor compliance and risk disinhibition), and the evolution of pathogen resistance. Here, we describe a proposed intervention that would overcome these challenges by capitalizing upon Therapeutic Interfering Particles (TIPs) that are engineered to replicate conditionally in the presence of the pathogen and spread between individuals — analogous to ‘transmissible immunization’ that occurs with live-attenuated vaccines (but without the potential for reversion to virulence). Building on analyses of HIV field data from sub-Saharan Africa, we construct a multi-scale model, beginning at the single-cell level, to predict the effect of TIPs on individual patient viral loads and ultimately population-level disease prevalence. Our results show that a TIP, engineered with properties based on a recent HIV gene-therapy trial, could stably lower HIV/AIDS prevalence by ∼30-fold within 50 years and could complement current therapies. In contrast, optimistic antiretroviral therapy or vaccination campaigns alone could only lower HIV/AIDS prevalence by <2-fold over 50 years. The TIP's efficacy arises from its exploitation of the same risk factors as the pathogen, allowing it to autonomously penetrate superspreader populations, maintain efficacy despite behavioral disinhibition, and limit viral resistance. While demonstrated here for HIV, the TIP concept could apply broadly to many viral infectious diseases and would represent a new paradigm for disease control, away from pathogen eradication but toward robust disease suppression.",2011 Mar 17,"['Metzger, Vincent T.', 'Lloyd-Smith, James O.', 'Weinberger, Leor S.']",PLoS Comput Biol,,,True
18fa3d1a5503e1943ce8e657416f9da8fe2cb475,PMC,Proteomic analysis of chicken embryonic trachea and kidney tissues after infection in ovo by avian infectious bronchitis coronavirus,http://dx.doi.org/10.1186/1477-5956-9-11,PMC3060854,21385394,CC BY,"BACKGROUND: Avian infectious bronchitis (IB) is one of the most serious diseases of economic importance in chickens; it is caused by the avian infectious coronavirus (IBV). Information remains limited about the comparative protein expression profiles of chicken embryonic tissues in response to IBV infection in ovo. In this study, we analyzed the changes of protein expression in trachea and kidney tissues from chicken embryos, following IBV infection in ovo, using two-dimensional gel electrophoresis (2-DE) coupled with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF-TOF MS). RESULTS: 17 differentially expressed proteins from tracheal tissues and 19 differentially expressed proteins from kidney tissues were identified. These proteins mostly related to the cytoskeleton, binding of calcium ions, the stress response, anti-oxidative, and macromolecular metabolism. Some of these altered proteins were confirmed further at the mRNA level using real-time RT-PCR. Moreover, western blotting analysis further confirmed the changes of annexin A5 and HSPB1 during IBV infection. CONCLUSIONS: To the best of our knowledge, we have performed the first analysis of the proteomic changes in chicken embryonic trachea and kidney tissues during IBV infection in ovo. The data obtained should facilitate a better understanding of the pathogenesis of IBV infection.",2011 Mar 8,"['Cao, Zhongzan', 'Han, Zongxi', 'Shao, Yuhao', 'Geng, Heyuan', 'Kong, Xiangang', 'Liu, Shengwang']",Proteome Sci,,,True
6efeb37a50a81c7769a49bcf030e54b148bd1fbd,PMC,Screening of Random Peptide Library of Hemagglutinin from Pandemic 2009 A(H1N1) Influenza Virus Reveals Unexpected Antigenically Important Regions,http://dx.doi.org/10.1371/journal.pone.0018016,PMC3060926,21437206,CC BY,"The antigenic structure of the membrane protein hemagglutinin (HA) from the 2009 A(H1N1) influenza virus was dissected with a high-throughput screening method using complex antisera. The approach involves generating yeast cell libraries displaying a pool of random peptides of controllable lengths on the cell surface, followed by one round of fluorescence-activated cell sorting (FACS) against antisera from mouse, goat and human, respectively. The amino acid residue frequency appearing in the antigenic peptides at both the primary sequence and structural level was determined and used to identify “hot spots” or antigenically important regions. Unexpectedly, different antigenic structures were seen for different antisera. Moreover, five antigenic regions were identified, of which all but one are located in the conserved HA stem region that is responsible for membrane fusion. Our findings are corroborated by several recent studies on cross-neutralizing H1 subtype antibodies that recognize the HA stem region. The antigenic peptides identified may provide clues for creating peptide vaccines with better accessibility to memory B cells and better induction of cross-neutralizing antibodies than the whole HA protein. The scheme used in this study enables a direct mapping of the antigenic regions of viral proteins recognized by antisera, and may be useful for dissecting the antigenic structures of other viral proteins.",2011 Mar 18,"['Xu, Wanghui', 'Han, Lu', 'Lin, Zhanglin']",PLoS One,,,True
d88b1e3e4d603dde6f344785e2371292e56f73a0,PMC,Proteomic analysis of swine serum following highly virulent classical swine fever virus infection,http://dx.doi.org/10.1186/1743-422X-8-107,PMC3061939,21385403,CC BY,"BACKGROUND: Classical swine fever virus (CSFV) belongs to the genus Pestivirus within the family Flaviviridae. Virulent strains of classical swine fever virus (CSFV) cause severe disease in pigs characterized by immunosuppression, thrombocytopenia and disseminated intravascular coagulation, which causes significant economic losses to the pig industry worldwide. METHODS: To reveal proteomic changes in swine serum during the acute stage of lethal CSFV infection, 5 of 10 pigs were inoculated with the virulent CSFV Shimen strain, the remainder serving as uninfected controls. A serum sample was taken at 3 days post-infection from each swine, at a stage when there were no clinical symptoms other than increased rectal temperatures (≥40°C). The samples were treated to remove serum albumin and immunoglobulin (IgG), and then subjected to two-dimension differential gel electrophoresis. RESULTS: Quantitative intensity analysis revealed 17 protein spots showing at least 1.5-fold quantitative alteration in expression. Ten spots were successfully identified by MALDI-TOF MS or LTQ MS. Expression of 4 proteins was increased and 6 decreased in CSFV-infected pigs. Functions of these proteins included blood coagulation, anti-inflammatory activity and angiogenesis. CONCLUSION: These proteins with altered expression may have important implications in the pathogenesis of classical swine fever and provide a clue for identification of biomarkers for classical swine fever early diagnosis.",2011 Mar 8,"['Sun, Jin-fu', 'Shi, Zi-xue', 'Guo, Huan-cheng', 'Li, Su', 'Tu, Chang-chun']",Virol J,,,True
62b348dd9761ec78af4d53ad162a747cd300edce,PMC,Vascular disrupting agent DMXAA enhances the antitumor effects generated by therapeutic HPV DNA vaccines,http://dx.doi.org/10.1186/1423-0127-18-21,PMC3062584,21385449,CC BY,"Antigen-specific immunotherapy using DNA vaccines has emerged as an attractive approach for the control of tumors. Another novel cancer therapy involves the employment of the vascular disrupting agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA). In the current study, we aimed to test the combination of DMXAA treatment with human papillomavirus type 16 (HPV-16) E7 DNA vaccination to enhance the antitumor effects and E7-specific CD8+ T cell immune responses in treated mice. We determined that treatment with DMXAA generates significant therapeutic effects against TC-1 tumors but does not enhance the antigen-specific immune responses in tumor bearing mice. We then found that combination of DMXAA treatment with E7 DNA vaccination generates potent antitumor effects and E7-specific CD8+ T cell immune responses in the splenocytes of tumor bearing mice. Furthermore, the DMXAA-mediated enhancement or suppression of E7-specific CD8+ T cell immune responses generated by CRT/E7 DNA vaccination was found to be dependent on the time of administration of DMXAA and was also applicable to other antigen-specific vaccines. In addition, we determined that inducible nitric oxide synthase (iNOS) plays a role in the immune suppression caused by DMXAA administration before DNA vaccination. Our study has significant implications for future clinical translation.",2011 Mar 8,"['Peng, Shiwen', 'Monie, Archana', 'Pang, Xiaowu', 'Hung, Chien-Fu', 'Wu, T-C']",J Biomed Sci,,,True
42f17b849628fb1db7c74cc15899bf9b9c59de93,PMC,Networks and the Epidemiology of Infectious Disease,http://dx.doi.org/10.1155/2011/284909,PMC3062985,21437001,CC BY,"The science of networks has revolutionised research into the dynamics of interacting elements. It could be argued that epidemiology in particular has embraced the potential of network theory more than any other discipline. Here we review the growing body of research concerning the spread of infectious diseases on networks, focusing on the interplay between network theory and epidemiology. The review is split into four main sections, which examine: the types of network relevant to epidemiology; the multitude of ways these networks can be characterised; the statistical methods that can be applied to infer the epidemiological parameters on a realised network; and finally simulation and analytical methods to determine epidemic dynamics on a given network. Given the breadth of areas covered and the ever-expanding number of publications, a comprehensive review of all work is impossible. Instead, we provide a personalised overview into the areas of network epidemiology that have seen the greatest progress in recent years or have the greatest potential to provide novel insights. As such, considerable importance is placed on analytical approaches and statistical methods which are both rapidly expanding fields. Throughout this review we restrict our attention to epidemiological issues.",2011 Mar 16,"['Danon, Leon', 'Ford, Ashley P.', 'House, Thomas', 'Jewell, Chris P.', 'Keeling, Matt J.', 'Roberts, Gareth O.', 'Ross, Joshua V.', 'Vernon, Matthew C.']",Interdiscip Perspect Infect Dis,,,True
e5f66769b3cbcb6b378257a7c83acdb1793a6803,PMC,Viral Encephalomyelitis,http://dx.doi.org/10.1371/journal.ppat.1002004,PMC3063766,21455493,CC BY,,2011 Mar 24,"Griffin, Diane E.",PLoS Pathog,,,True
c05da515acecfc66d0b0b7a46a51e557cb9bb08d,PMC,Assessing the In Vitro Fitness of an Oseltamivir-Resistant Seasonal A/H1N1 Influenza Strain Using a Mathematical Model,http://dx.doi.org/10.1371/journal.pone.0014767,PMC3063785,21455300,CC BY,"In 2007, the A/Brisbane/59/2007 (H1N1) seasonal influenza virus strain acquired the oseltamivir-resistance mutation H275Y in its neuraminidase (NA) gene. Although previous studies had demonstrated that this mutation impaired the replication capacity of the influenza virus in vitro and in vivo, the A/Brisbane/59/2007 H275Y oseltamivir-resistant mutant completely out-competed the wild-type (WT) strain and was, in the 2008–2009 influenza season, the primary A/H1N1 circulating strain. Using a combination of plaque and viral yield assays, and a simple mathematical model, approximate values were extracted for two basic viral kinetics parameters of the in vitro infection. In the ST6GalI-MDCK cell line, the latent infection period (i.e., the time for a newly infected cell to start releasing virions) was found to be 1–3 h for the WT strain and more than 7 h for the H275Y mutant. The infecting time (i.e., the time for a single infectious cell to cause the infection of another one) was between 30 and 80 min for the WT, and less than 5 min for the H275Y mutant. Single-cycle viral yield experiments have provided qualitative confirmation of these findings. These results, though preliminary, suggest that the increased fitness success of the A/Brisbane/59/2007 H275Y mutant may be due to increased infectivity compensating for an impaired or delayed viral release, and are consistent with recent evidence for the mechanistic origins of fitness reduction and recovery in NA expression. The method applied here can reconcile seemingly contradictory results from the plaque and yield assays as two complementary views of replication kinetics, with both required to fully capture a strain's fitness.",2011 Mar 24,"['Holder, Benjamin P.', 'Simon, Philippe', 'Liao, Laura E.', 'Abed, Yacine', 'Bouhy, Xavier', 'Beauchemin, Catherine A. A.', 'Boivin, Guy']",PLoS One,,,True
73ae7423efc653849fa7d2b6b2770164dd02b2c1,PMC,"Viral Etiologies of Acute Respiratory Infections among Hospitalized Vietnamese Children in Ho Chi Minh City, 2004–2008",http://dx.doi.org/10.1371/journal.pone.0018176,PMC3063798,21455313,CC BY,"BACKGROUND: The dominant viral etiologies responsible for acute respiratory infections (ARIs) are poorly understood, particularly among hospitalized children in resource-limited tropical countries where morbidity and mortality caused by ARIs are highest. Improved etiological insight is needed to improve clinical management and prevention. OBJECTIVES: We conducted a three-year prospective descriptive study of severe respiratory illness among children from 2 months to 13 years of age within the largest referral hospital for infectious diseases in southern Vietnam. METHODS: Molecular detection for 15 viral species and subtypes was performed on three types of respiratory specimens (nose, throat swabs and nasopharyngeal aspirates) using a multiplex RT-PCR kit (Seeplex™ RV detection, Seegene) and additional monoplex real-time RT-PCRs. RESULTS: A total of 309 children were enrolled from November 2004 to January 2008. Viruses were identified in 72% (222/309) of cases, including respiratory syncytial virus (24%), influenza virus A and B (17%), human bocavirus (16%), enterovirus (9%), human coronavirus (8%), human metapneumovirus (7%), parainfluenza virus 1–3 (6%), adenovirus (5%), and human rhinovirus A (4%). Co-infections with multiple viruses were detected in 20% (62/309) of patients. When combined, diagnostic yields in nose and throat swabs were similar to nasopharyngeal aspirates. CONCLUSION: Similar to other parts in the world, RSV and influenza were the predominant viral pathogens detected in Vietnamese hospitalized children. Combined nasal and throat swabs are the specimens of choice for sensitive molecular detection of a broad panel of viral agents. Further research is required to better understand the clinical significance of single versus multiple viral coinfections and to address the role of bacterial (co-)infections involved in severe respiratory illness.",2011 Mar 24,"['Do, Anh Ha Lien', 'van Doorn, H. Rogier', 'Nghiem, My Ngoc', 'Bryant, Juliet E.', 'Hoang, Thanh Hang thi', 'Do, Quang Ha', 'Le Van, Tan', 'Tran, Tan Thanh', 'Wills, Bridget', 'van Nguyen, Vinh Chau', 'Vo, Minh Hien', 'Vo, Cong Khanh', 'Nguyen, Minh Dung', 'Farrar, Jeremy', 'Tran, Tinh Hien', 'de Jong, Menno D.']",PLoS One,,,True
048b240dcabbd623a6cda8c4236ea50d7961315c,PMC,The Role of Thailand in the International Trade in CITES-Listed Live Reptiles and Amphibians,http://dx.doi.org/10.1371/journal.pone.0017825,PMC3064566,21464976,CC BY,"BACKGROUND: International wildlife trade is one of the leading threats to biodiversity conservation. The Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) is the most important initiative to monitor and regulate the international trade of wildlife but its credibility is dependent on the quality of the trade data. We report on the performance of CITES reporting by focussing on the commercial trade in non-native reptiles and amphibians into Thailand as to illustrate trends, species composition and numbers of wild-caught vs. captive-bred specimens. METHODOLOGY/PRINCIPAL FINDINGS: Based on data in the WCMC-CITES trade database, we establish that a total of 75,594 individuals of 169 species of reptiles and amphibians (including 27 globally threatened species) were imported into Thailand in 1990–2007. The majority of individuals (59,895, 79%) were listed as captive-bred and a smaller number (15,699, 21%) as wild-caught. In the 1990s small numbers of individuals of a few species were imported into Thailand, but in 2003 both volumes and species diversity increased rapidly. The proportion of captive-bred animals differed greatly between years (from 0 to >80%). Wild-caught individuals were mainly sourced from African countries, and captive-bred individuals from Asian countries (including from non-CITES Parties). There were significant discrepancies between exports and imports. Thailand reports the import of >10,000 individuals (51 species) originating from Kazakhstan, but Kazakhstan reports no exports of these species. Similar discrepancies, involving smaller numbers (>100 individuals of 9 species), can be seen in the import of reptiles into Thailand via Macao. CONCLUSION/SIGNIFICANCE: While there has been an increase in imports of amphibian and reptiles into Thailand, erratic patterns in proportions of captive-bred specimens and volumes suggests either capricious markets or errors in reporting. Large discrepancies with respect to origin point to misreporting or possible violations of the rules and intentions of CITES.",2011 Mar 25,"['Nijman, Vincent', 'Shepherd, Chris R.']",PLoS One,,,True
6cc30d377f0bd9004378ef98ef2b7c145a79711e,PMC,"Genomic Signatures of Strain Selection and Enhancement in Bacillus atrophaeus var. globigii, a Historical Biowarfare Simulant",http://dx.doi.org/10.1371/journal.pone.0017836,PMC3064580,21464989,CC0,"BACKGROUND: Despite the decades-long use of Bacillus atrophaeus var. globigii (BG) as a simulant for biological warfare (BW) agents, knowledge of its genome composition is limited. Furthermore, the ability to differentiate signatures of deliberate adaptation and selection from natural variation is lacking for most bacterial agents. We characterized a lineage of BGwith a long history of use as a simulant for BW operations, focusing on classical bacteriological markers, metabolic profiling and whole-genome shotgun sequencing (WGS). RESULTS: Archival strains and two “present day” type strains were compared to simulant strains on different laboratory media. Several of the samples produced multiple colony morphotypes that differed from that of an archival isolate. To trace the microevolutionary history of these isolates, we obtained WGS data for several archival and present-day strains and morphotypes. Bacillus-wide phylogenetic analysis identified B. subtilis as the nearest neighbor to B. atrophaeus. The genome of B. atrophaeus is, on average, 86% identical to B. subtilis on the nucleotide level. WGS of variants revealed that several strains were mixed but highly related populations and uncovered a progressive accumulation of mutations among the “military” isolates. Metabolic profiling and microscopic examination of bacterial cultures revealed enhanced growth of “military” isolates on lactate-containing media, and showed that the “military” strains exhibited a hypersporulating phenotype. CONCLUSIONS: Our analysis revealed the genomic and phenotypic signatures of strain adaptation and deliberate selection for traits that were desirable in a simulant organism. Together, these results demonstrate the power of whole-genome and modern systems-level approaches to characterize microbial lineages to develop and validate forensic markers for strain discrimination and reveal signatures of deliberate adaptation.",2011 Mar 25,"['Gibbons, Henry S.', 'Broomall, Stacey M.', 'McNew, Lauren A.', 'Daligault, Hajnalka', 'Chapman, Carol', 'Bruce, David', 'Karavis, Mark', 'Krepps, Michael', 'McGregor, Paul A.', 'Hong, Charles', 'Park, Kyong H.', 'Akmal, Arya', 'Feldman, Andrew', 'Lin, Jeffrey S.', 'Chang, Wenling E.', 'Higgs, Brandon W.', 'Demirev, Plamen', 'Lindquist, John', 'Liem, Alvin', 'Fochler, Ed', 'Read, Timothy D.', 'Tapia, Roxanne', 'Johnson, Shannon', 'Bishop-Lilly, Kimberly A.', 'Detter, Chris', 'Han, Cliff', 'Sozhamannan, Shanmuga', 'Rosenzweig, C. Nicole', 'Skowronski, Evan W.']",PLoS One,,,True
9d4ce1e58828bc78c7c83f40c14765df96feb277,PMC,Differential Induction of Functional IgG Using the Plasmodium falciparum Placental Malaria Vaccine Candidate VAR2CSA,http://dx.doi.org/10.1371/journal.pone.0017942,PMC3064590,21464946,CC BY,"BACKGROUND: In Plasmodium falciparum malaria endemic areas placental malaria (PM) is an important complication of malaria. The recurrence of malaria in primigravidae women irrespective of acquired protection during childhood is caused by the interaction between the parasite-expressed VAR2CSA antigen and chondroitin sulfate A (CSA) in the placental intervillous space and lack of protective antibodies. PM impairs fetal development mainly by excessive inflammation processes. After infections during pregnancy women acquire immunity to PM conferred by antibodies against VAR2CSA. Ideally, a vaccine against PM will induce antibody-mediated immune responses that block the adhesion of infected erythrocytes (IE) in the placenta. PRINCIPAL FINDINGS: We have previously shown that antibodies raised in rat against individual domains of VAR2CSA can block IE binding to CSA. In this study we have immunized mice, rats and rabbits with each individual domain and the full-length protein corresponding to the FCR3 VAR2CSA variant. We found there is an inherently higher immunogenicity of C-terminal domains compared to N-terminally located domains. This was irrespective of whether antibodies were induced against single domains or the full-length protein. Species-specific antibody responses were also found, these were mainly directed against single domains and not the full-length VAR2CSA protein. CONCLUSIONS/SIGNIFICANCE: Binding inhibitory antibodies appeared to be against conformational B-cell epitopes. Non-binding inhibitory antibodies reacted highly against the C-terminal end of the VAR2CSA molecule especially the highly polymorphic DBL6ε domain. Differential species-specific induction of antibody responses may allow for more direct analysis of functional versus non-functional B-cell epitopes.",2011 Mar 25,"['Pinto, Vera V.', 'Ditlev, Sisse B.', 'Jensen, Kamilla E.', 'Resende, Mafalda', 'Dahlbäck, Madeleine', 'Andersen, Gorm', 'Andersen, Pernille', 'Theander, Thor G.', 'Salanti, Ali', 'Nielsen, Morten A.']",PLoS One,,,True
c883fc2c4774529ce853012e339acf2aadc53454,PMC,Human rhinovirus infection in young African children with acute wheezing,http://dx.doi.org/10.1186/1471-2334-11-65,PMC3065410,21401965,CC BY,"BACKGROUND: Infections caused by human rhinoviruses (HRVs) are important triggers of wheezing in young children. Wheezy illness has increasingly been recognised as an important cause of morbidity in African children, but there is little information on the contribution of HRV to this. The aim of this study was to determine the role of HRV as a cause of acute wheezing in South African children. METHODS: Two hundred and twenty children presenting consecutively at a tertiary children's hospital with a wheezing illness from May 2004 to November 2005 were prospectively enrolled. A nasal swab was taken and reverse transcription PCR used to screen the samples for HRV. The presence of human metapneumovirus, human bocavirus and human coronavirus-NL63 was assessed in all samples using PCR-based assays. A general shell vial culture using a pool of monoclonal antibodies was used to detect other common respiratory viruses on 26% of samples. Phylogenetic analysis to determine circulating HRV species was performed on a portion of HRV-positive samples. Categorical characteristics were analysed using Fisher's Exact test. RESULTS: HRV was detected in 128 (58.2%) of children, most (72%) of whom were under 2 years of age. Presenting symptoms between the HRV-positive and negative groups were similar. Most illness was managed with ambulatory therapy, but 45 (35%) were hospitalized for treatment and 3 (2%) were admitted to intensive care. There were no in-hospital deaths. All 3 species of HRV were detected with HRV-C being the most common (52%) followed by HRV-A (37%) and HRV-B (11%). Infection with other respiratory viruses occurred in 20/128 (16%) of HRV-positive children and in 26/92 (28%) of HRV-negative samples. CONCLUSION: HRV may be the commonest viral infection in young South African children with acute wheezing. Infection is associated with mild or moderate clinical disease.",2011 Mar 15,"['Smuts, Heidi E', 'Workman, Lesley J', 'Zar, Heather J']",BMC Infect Dis,,,True
6fad5703e838cae052bc9cd18b32ea812b942fb4,PMC,A Transient Homotypic Interaction Model for the Influenza A Virus NS1 Protein Effector Domain,http://dx.doi.org/10.1371/journal.pone.0017946,PMC3065461,21464929,CC BY,"Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal ‘tail’. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed ‘helix-closed’ and ‘helix-open’) in virus-infected cells. ‘Helix-closed’ conformations appear to enhance dsRNA binding, and ‘helix-open’ conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins.",2011 Mar 28,"['Kerry, Philip S.', 'Ayllon, Juan', 'Taylor, Margaret A.', 'Hass, Claudia', 'Lewis, Andrew', 'García-Sastre, Adolfo', 'Randall, Richard E.', 'Hale, Benjamin G.', 'Russell, Rupert J.']",PLoS One,,,True
335f41145ff784047aa5a0ae829be50613c65038,PMC,Is Generalized Maternal Optimism or Pessimism During Pregnancy Associated with Unplanned Cesarean Section Deliveries in China?,http://dx.doi.org/10.1155/2010/754938,PMC3065811,21490743,CC BY,"This research examines whether maternal optimism/pessimism is associated with unplanned Cesarean section deliveries in China. If so, does the association remain after controlling for clinical factors associated with C-sections? A sample of 227 mostly primiparous women in the third trimester of pregnancy was surveyed in a large tertiary care hospital in Beijing, China. Post-delivery data were collected from medical records. In bivariate analysis, both optimism and pessimism were related to unplanned c-section. However, when optimism and pessimism were entered into a regression model together, optimism was no longer statistically significant. Pessimism remained significant, even when adjusting for clinical factors such as previous abortion, previous miscarriage, pregnancy complications, infant gestational age, infant birthweight, labor duration, birth complications, and self-rated difficulty of the pregnancy. This research suggests that maternal mindset during pregnancy has a role in mode of delivery. However, more research is needed to elucidate potential causal pathways and test potential interventions.",2010 Jan 5,"['Moyer, Cheryl A.', 'Elsayed, Yasmin', 'Zhu, YuChun', 'Wei, Yumei', 'Engmann, Cyril M.', 'Yang, Huixia']",J Pregnancy,,,True
b6b73f121cfd9d486f77bae744fa2a7e09df51f4,PMC,In Vitro Gene Delivery Mediated by Asialofetuin-Appended Cationic Liposomes Associated with γ-Cyclodextrin into Hepatocytes,http://dx.doi.org/10.1155/2011/476137,PMC3065884,21490752,CC BY,"The purpose of this study is to evaluate in vitro gene delivery mediated by asialofetuin-appended cationic liposomes (AF-liposomes) associating cyclodextrins (CyD/AF-liposomes) as a hepatocyte-selective nonviral vector. Of various CyDs, AF-liposomes associated with plasmid DNA (pDNA) and γ-cyclodextrin (γ-CyD) (pDNA/γ-CyD/AF-liposomes) showed the highest gene transfer activity in HepG2 cells without any significant cytotoxicity. In addition, γ-CyD enhanced the encapsulation ratio of pDNA with AF-liposomes, and also increased gene transfer activity as the entrapment ratio of pDNA into AF-liposomes was increased. γ-CyD stabilized the liposomal membrane of AF-liposomes and inhibited the release of calcein from AF-liposomes. The stabilizing effect of γ-CyD may be, at least in part, involved in the enhancing gene transfer activity of pDNA/γ-CyD/AF-liposomes. Therefore, these results suggest the potential use of γ-CyD for an enhancer of transfection efficiency of AF-liposomes.",2011 Dec 9,"['Motoyama, Keiichi', 'Nakashima, Yoshihiro', 'Aramaki, Yukihiko', 'Hirayama, Fumitoshi', 'Uekama, Kaneto', 'Arima, Hidetoshi']",J Drug Deliv,,,True
1968f8d8ffe3f695372d919c9966b1ca412b83d2,PMC,Induction of Cyclooxygenase-2 Expression by Hepatitis B Virus Depends on Demethylation-associated Recruitment of Transcription Factors to the Promoter,http://dx.doi.org/10.1186/1743-422X-8-118,PMC3066118,21401943,CC BY,"BACKGROUND: The hepatitis B virus (HBV) is a major etiological factor of inflammation and damage to the liver resulting in hepatocellular carcinoma. Transcription factors play important roles in the disordered gene expression and liver injury caused by HBV. However, the molecular mechanisms behind this observation have not been defined. RESULTS: In this study, we observed that circulating prostaglandin (PGE) 2 synthesis was increased in patients with chronic hepatitis B infection, and detected elevated cyclooxygenase (COX)-2 expression in HBV- and HBx-expressing liver cells. Likewise, the association of HBx with C/EBPβ contributed to the induction of COX-2. The COX-2 promoter was hypomethylated in HBV-positive cells, and specific demethylation of CpG dinucleotides within each of the two NF-AT sites in the COX-2 promoter resulted in the increased binding affinity of NF-AT to the cognate sites in the promoter, followed by increased COX-2 expression and PGE2 accumulation. The DNA methylatransferase DNMT3B played a key role in the methylation of the COX-2 promoter, and its decreased binding to the promoter was responsible for the regional demethylation of CpG sites, and for the increased binding of transcription factors in HBV-positive cells. CONCLUSION: Our results indicate that upregulation of COX-2 by HBV and HBx is mediated by both demethylation events and recruitment of multiple transcription factors binding to the promoter.",2011 Mar 14,"['Yue, Xin', 'Yang, Fang', 'Yang, Yongbo', 'Mu, Yongxin', 'Sun, Wei', 'Li, Wei', 'Xu, Dongping', 'Wu, Jianguo', 'Zhu, Ying']",Virol J,,,True
ff6b55c00278cf8081dec1ad430940165b23d91e,PMC,Human Rhinovirus Infections in Rural Thailand: Epidemiological Evidence for Rhinovirus as Both Pathogen and Bystander,http://dx.doi.org/10.1371/journal.pone.0017780,PMC3066183,21479259,CC0,"BACKGROUND: We describe human rhinovirus (HRV) detections in SaKaeo province, Thailand. METHODS: From September 1, 2003–August 31, 2005, we tested hospitalized patients with acute lower respiratory illness and outpatient controls without fever or respiratory symptoms for HRVs with polymerase chain reaction and molecularly-typed select HRVs. We compared HRV detection among hospitalized patients and controls and estimated enrollment adjusted incidence. RESULTS: HRVs were detected in 315 (16%) of 1919 hospitalized patients and 27 (9.6%) of 280 controls. Children had the highest frequency of HRV detections (hospitalized: <1 year: 29%, 1–4 year: 29%, ≥65 years: 9%; controls: <1 year: 24%, 1–4 year: 14%, ≥65 years: 2.8%). Enrollment adjusted hospitalized HRV detection rates were highest among persons aged <1 year (1038/100,000 persons/year), 1–4 years (457), and ≥65 years (71). All three HRV species were identified, HRV-A was the most common species in most age groups including children aged <1 year (61%) and all adult age groups. HRV-C was the most common species in the 1–4 year (51%) and 5–19 year age groups (54%). Compared to controls, hospitalized adults (≥19 years) and children were more likely to have HRV detections (odds ratio [OR]: 4.8, 95% confidence interval [CI]: 1.5, 15.8; OR: 2.0, CI: 1.2, 3.3, respectively) and hospitalized children were more likely to have HRV-A (OR 1.7, CI: 0.8, 3.5) or HVR-C (OR 2.7, CI: 1.2, 5.9) detection. CONCLUSIONS: HRV rates were high among hospitalized children and the elderly but asymptomatic children also had substantial HRV detection. HRV (all species), and HRV-A and HRV-C detections were epidemiologically-associated with hospitalized illness. Treatment or prevention modalities effective against HRV could reduce hospitalizations due to HRV in Thailand.",2011 Mar 29,"['Fry, Alicia M.', 'Lu, Xiaoyan', 'Olsen, Sonja J.', 'Chittaganpitch, Malinee', 'Sawatwong, Pongpun', 'Chantra, Somrak', 'Baggett, Henry C.', 'Erdman, Dean']",PLoS One,,,True
f82bb9d2d37888e87a1f8f42c7f898a809c3bc94,PMC,A Mutation in Myo15 Leads to Usher-Like Symptoms in LEW/Ztm-ci2 Rats,http://dx.doi.org/10.1371/journal.pone.0015669,PMC3066203,21479269,CC BY,"The LEW/Ztm-ci2 rat is an animal model for syndromal deafness that arose from a spontaneous mutation. Homozygous animals show locomotor abnormalities like lateralized circling behavior. Additionally, an impaired vision can be observed in some animals through behavioral studies. Syndromal deafness as well as retinal degeneration are features of the Usher syndrome in humans. In the present study, the mutation was identified as a base substitution (T->C) in exon 56 of Myo15, leading to an amino acid exchange from leucine (Leu) to proline (Pro) within the carboxy-terminal MyTH4 domain in the proteins' tail region. Myo15 mRNA was expressed in the retina as demonstrated for the first time with the help of in-situ hybridization and PCR. To characterize the visual phenotype, rats were examined by scotopic and photopic electroretinography and, additionally, histological analyses of the retinas were conducted. The complete loss of sight was detected along with a severe degeneration of photoreceptor cells. Interestingly, the manifestation of the disease does not solely depend on the mutation, but also on environmental factors. Since the LEW/Ztm-ci2 rat features the entire range of symptoms of the human Usher syndrome we think that this strain is an appropriate model for this disease. Our findings display that mutations in binding domains of myosin XV do not only cause non-syndromic hearing loss but can also lead to syndromic disorders including retinal dysfunction.",2011 Mar 29,"['Held, Nadine', 'Smits, Bart M. G.', 'Gockeln, Roland', 'Schubert, Stephanie', 'Nave, Heike', 'Northrup, Emily', 'Cuppen, Edwin', 'Hedrich, Hans J.', 'Wedekind, Dirk']",PLoS One,,,True
8996c8a004bc82aca37ba1f1f4265868503ce69f,PMC,Participation of the Cell Polarity Protein PALS1 to T-Cell Receptor-Mediated NF-κB Activation,http://dx.doi.org/10.1371/journal.pone.0018159,PMC3068181,21479189,CC BY,"BACKGROUND: Beside their established function in shaping cell architecture, some cell polarity proteins were proposed to participate to lymphocyte migration, homing, scanning, as well as activation following antigen receptor stimulation. Although PALS1 is a central component of the cell polarity network, its expression and function in lymphocytes remains unknown. Here we investigated whether PALS1 is present in T cells and whether it contributes to T Cell-Receptor (TCR)-mediated activation. METHODOLOGY/PRINCIPAL FINDINGS: By combining RT-PCR and immunoblot assays, we found that PALS1 is constitutively expressed in human T lymphocytes as well as in Jurkat T cells. siRNA-based knockdown of PALS1 hampered TCR-induced activation and optimal proliferation of lymphocyte. We further provide evidence that PALS1 depletion selectively hindered TCR-driven activation of the transcription factor NF-κB. CONCLUSIONS: The cell polarity protein PALS1 is expressed in T lymphocytes and participates to the optimal activation of NF-κB following TCR stimulation.",2011 Mar 30,"['Carvalho, Gabrielle', 'Poalas, Konstantinos', 'Demian, Catherine', 'Hatchi, Emeline', 'Vazquez, Aimé', 'Bidère, Nicolas']",PLoS One,,,True
a7c6ab514af0b9e5edc73e08e496ceb65111cfa9,PMC,A Canadian Critical Care Trials Group project in collaboration with the international forum for acute care trialists - Collaborative H1N1 Adjuvant Treatment pilot trial (CHAT): study protocol and design of a randomized controlled trial,http://dx.doi.org/10.1186/1745-6215-12-70,PMC3068961,21388549,CC BY,"BACKGROUND: Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes. METHODS/DESIGN: A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to medication administration regimens, the proportion of primary and secondary endpoints collected, the number of patients receiving open-label statins, consent withdrawals and the effect of approved consent models on recruitment rates. DISCUSSION: Several aspects of study design including the need to include central randomization, preserve allocation concealment, ensure study blinding compare to a matched placebo and the use novel consent models pose challenges to investigators conducting pandemic research. Moreover, study implementation requires that trial design be pragmatic and initiated in a short time period amidst uncertainty regarding the scope and duration of the pandemic. TRIAL REGISTRATION NUMBER: ISRCTN45190901",2011 Mar 9,"['Burns, Karen EA', 'Chant, Clarence', 'Smith, Orla', 'Cuthbertson, Brian', 'Fowler, Robert', 'Cook, Deborah J', 'Kruger, Peter', 'Webb, Steve', 'Alhashemi, Jamal', 'Dominguez-Cherit, Guillermo', 'Zala, Carlos', 'Rubenfeld, Gordon D', 'Marshall, John C']",Trials,,,True
335e894a725e26adfe71b89170e3fc1301eafb1c,PMC,Dissection of the Influenza A Virus Endocytic Routes Reveals Macropinocytosis as an Alternative Entry Pathway,http://dx.doi.org/10.1371/journal.ppat.1001329,PMC3068995,21483486,CC BY,"Influenza A virus (IAV) enters host cells upon binding of its hemagglutinin glycoprotein to sialylated host cell receptors. Whereas dynamin-dependent, clathrin-mediated endocytosis (CME) is generally considered as the IAV infection pathway, some observations suggest the occurrence of an as yet uncharacterized alternative entry route. By manipulating entry parameters we established experimental conditions that allow the separate analysis of dynamin-dependent and -independent entry of IAV. Whereas entry of IAV in phosphate-buffered saline could be completely inhibited by dynasore, a specific inhibitor of dynamin, a dynasore-insensitive entry pathway became functional in the presence of fetal calf serum. This finding was confirmed with the use of small interfering RNAs targeting dynamin-2. In the presence of serum, both IAV entry pathways were operational. Under these conditions entry could be fully blocked by combined treatment with dynasore and the amiloride derivative EIPA, the hallmark inhibitor of macropinocytosis, whereas either drug alone had no effect. The sensitivity of the dynamin-independent entry pathway to inhibitors or dominant-negative mutants affecting actomyosin dynamics as well as to a number of specific inhibitors of growth factor receptor tyrosine kinases and downstream effectors thereof all point to the involvement of macropinocytosis in IAV entry. Consistently, IAV particles and soluble FITC-dextran were shown to co-localize in cells in the same vesicles. Thus, in addition to the classical dynamin-dependent, clathrin-mediated endocytosis pathway, IAV enters host cells by a dynamin-independent route that has all the characteristics of macropinocytosis.",2011 Mar 31,"['de Vries, Erik', 'Tscherne, Donna M.', 'Wienholts, Marleen J.', 'Cobos-Jiménez, Viviana', 'Scholte, Florine', 'García-Sastre, Adolfo', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.']",PLoS Pathog,,,True
b3751edcd573ad46664235ecd8b63e9db99d4c09,PMC,Alpha-COPI Coatomer Protein Is Required for Rough Endoplasmic Reticulum Whorl Formation in Mosquito Midgut Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0018150,PMC3069061,21483820,CC BY,"BACKGROUND: One of the early events in midgut epithelial cells of Aedes aegypti mosquitoes is the dynamic reorganization of rough endoplasmic reticulum (RER) whorl structures coincident with the onset of blood meal digestion. Based on our previous studies showing that feeding on an amino acid meal induces TOR signaling in Ae. aegypti, we used proteomics and RNAi to functionally identify midgut epithelial cell proteins that contribute to RER whorl formation. METHODOLOGY/PRINCIPAL FINDINGS: Adult female Ae. aegypti mosquitoes were maintained on sugar alone (unfed), or fed an amino acid meal, and then midgut epithelial cells were analyzed by electron microscopy and protein biochemistry. The size and number of RER whorls in midgut epithelial cells were found to decrease significantly after feeding, and several KDEL-containing proteins were shown to have altered expression levels. LC-MS/MS mass spectrometry was used to analyze midgut microsomal proteins isolated from unfed and amino acid fed mosquitoes, and of the 127 proteins identified, 8 were chosen as candidate whorl forming proteins. Three candidate proteins were COPI coatomer subunits (alpha, beta, beta'), all of which appeared to be present at higher levels in microsomal fractions from unfed mosquitoes. Using RNAi to knockdown alpha-COPI expression, electron microscopy revealed that both the size and number of RER whorls were dramatically reduced in unfed mosquitoes, and moreover, that extended regions of swollen RER were prevalent in fed mosquitoes. Lastly, while a deficiency in alpha-COPI had no effect on early trypsin protein synthesis or secretion 3 hr post blood meal (PBM), expression of late phase proteases at 24 hr PBM was completely blocked. CONCLUSIONS: alpha-COPI was found to be required for the formation of RER whorls in midgut epithelial cells of unfed Aa. aegypti mosquitoes, as well as for the expression of late phase midgut proteases.",2011 Mar 31,"['Zhou, Guoli', 'Isoe, Jun', 'Day, W. Antony', 'Miesfeld, Roger L.']",PLoS One,,,True
da263831b51c583027932f156c45463780ea35fe,PMC,"Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study",http://dx.doi.org/10.1186/1471-2377-11-37,PMC3071317,21435231,CC BY,"BACKGROUND: The long term adverse effects of Severe Acute Respiratory Syndrome (SARS), a viral disease, are poorly understood. METHODS: Sleep physiology, somatic and mood symptoms of 22 Toronto subjects, 21 of whom were healthcare workers, (19 females, 3 males, mean age 46.29 yrs.+/- 11.02) who remained unable to return to their former occupation (mean 19.8 months, range: 13 to 36 months following SARS) were compared to 7 healthy female subjects. Because of their clinical similarities to patients with fibromyalgia syndrome (FMS) these post-SARS subjects were similarly compared to 21 drug free female patients, (mean age 42.4 +/- 11.8 yrs.) who fulfilled criteria for fibromyalgia. RESULTS: Chronic post-SARS is characterized by persistent fatigue, diffuse myalgia, weakness, depression, and nonrestorative sleep with associated REM-related apneas/hypopneas, an elevated sleep EEG cyclical alternating pattern, and alpha EEG sleep anomaly. Post- SARS patients had symptoms of pre and post-sleep fatigue and post sleep sleepiness that were similar to the symptoms of patients with FMS, and similar to symptoms of patients with chronic fatigue syndrome. Both post-SARS and FMS groups had sleep instability as indicated by the high sleep EEG cyclical alternating pattern rate. The post-SARS group had a lower rating of the alpha EEG sleep anomaly as compared to the FMS patients. The post-SARS group also reported less pre-sleep and post-sleep musculoskeletal pain symptoms. CONCLUSIONS: The clinical and sleep features of chronic post-SARS form a syndrome of chronic fatigue, pain, weakness, depression and sleep disturbance, which overlaps with the clinical and sleep features of FMS and chronic fatigue syndrome.",2011 Mar 24,"['Moldofsky, Harvey', 'Patcai, John']",BMC Neurol,,,True
828433debf53d822b26035b951ec78a6f3009de1,PMC,"Vomiting and wasting disease associated with hemagglutinating encephalomyelitis viruses infection in piglets in jilin, china",http://dx.doi.org/10.1186/1743-422X-8-130,PMC3071789,21418610,CC BY,"One coronavirus strain was isolated from brain tissues of ten piglets with evident clinical manifestations of vomiting, diarrhea and dyskinesia in Jilin province in China. Antigenic and genomic characterizations of the virus (isolate PHEV-JLsp09) were based on multiplex PCR and negative staining electron microscopy and sequence analysis of the Hemagglutinin-esterase (HE) gene. These piglets were diagnosed with Porcine hemagglutinating encephalomyelitis virus (PHEV). Necropsy was performed on the piglets. Major pathological changes included meningeal hyperemia, meningeal hemorrhage and cortical hemorrhage. Minor changes were also observed in other organs. Histopathological changes included satellitosis and neuronophagia in the cerebral cortex. Mice were infected with the isolated virus. Their histopathological changes were similar to those symptoms observed in the piglets, exhibiting typical changes for non-suppurative encephalitis. Thus, Porcine hemagglutinating encephalomyelitis virus mainly causes damage to the nervous system but also impacts other organs. This viral strain (isolate PHEV-JLsp09) found in the Siping area of Jilin Province in China is evolutionally closest to the HEV-67N stain (North American strain), indicating that this viral strain evolved from the PHEV from North America.",2011 Mar 21,"['Gao, Wei', 'Zhao, Kui', 'Zhao, Chuanbo', 'Du, Chongtao', 'Ren, Wenzhi', 'Song, Deguang', 'Lu, Huijun', 'Chen, Keyan', 'Li, Zhiping', 'Lan, Yungang', 'Xie, Shengnan', 'He, Wenqi', 'Gao, Feng']",Virol J,,,True
64fe1b9afa90e2e1ea0c1c10e2ae5ada566e270a,PMC,"Genetic characterization of avian influenza subtype H4N6 and H4N9 from live bird market, Thailand",http://dx.doi.org/10.1186/1743-422X-8-131,PMC3071790,21418614,CC BY,"A one year active surveillance program for influenza A viruses among avian species in a live-bird market (LBM) in Bangkok, Thailand was conducted in 2009. Out of 970 samples collected, influenza A virus subtypes H4N6 (n = 2) and H4N9 (n = 1) were isolated from healthy Muscovy ducks. All three viruses were characterized by whole genome sequencing with subsequent phylogenetic analysis and genetic comparison. Phylogenetic analysis of all eight viral genes showed that the viruses clustered in the Eurasian lineage of influenza A viruses. Genetic analysis showed that H4N6 and H4N9 viruses display low pathogenic avian influenza characteristics. The HA cleavage site and receptor binding sites were conserved and resembled to LPAI viruses. This study is the first to report isolation of H4N6 and H4N9 viruses from birds in LBM in Thailand and shows the genetic diversity of the viruses circulating in the LBM. In addition, co-infection of H4N6 and H4N9 in the same Muscovy duck was observed.",2011 Mar 21,"['Wisedchanwet, Trong', 'Wongphatcharachai  , Manoosak', 'Boonyapisitsopa, Supanat', 'Bunpapong, Napawan', 'Kitikoon, Pravina', 'Amonsin, Alongkorn']",Virol J,,,True
475c8599530b970bbf476ee0e2798f5940dc1254,PMC,Vaccine Potential of Nipah Virus-Like Particles,http://dx.doi.org/10.1371/journal.pone.0018437,PMC3071823,21494680,CC BY,"Nipah virus (NiV) was first recognized in 1998 in a zoonotic disease outbreak associated with highly lethal febrile encephalitis in humans and a predominantly respiratory disease in pigs. Periodic deadly outbreaks, documentation of person-to-person transmission, and the potential of this virus as an agent of agroterror reinforce the need for effective means of therapy and prevention. In this report, we describe the vaccine potential of NiV virus-like particles (NiV VLPs) composed of three NiV proteins G, F and M. Co-expression of these proteins under optimized conditions resulted in quantifiable amounts of VLPs with many virus-like/vaccine desirable properties including some not previously described for VLPs of any paramyxovirus: The particles were fusogenic, inducing syncytia formation; PCR array analysis showed NiV VLP-induced activation of innate immune defense pathways; the surface structure of NiV VLPs imaged by cryoelectron microscopy was dense, ordered, and repetitive, and consistent with similarly derived structure of paramyxovirus measles virus. The VLPs were composed of all the three viral proteins as designed, and their intracellular processing also appeared similar to NiV virions. The size, morphology and surface composition of the VLPs were consistent with the parental virus, and importantly, they retained their antigenic potential. Finally, these particles, formulated without adjuvant, were able to induce neutralizing antibody response in Balb/c mice. These findings indicate vaccine potential of these particles and will be the basis for undertaking future protective efficacy studies in animal models of NiV disease.",2011 Apr 6,"['Walpita, Pramila', 'Barr, Jennifer', 'Sherman, Michael', 'Basler, Christopher F.', 'Wang, Linfa']",PLoS One,,,True
417006f8744a4d8068ce146b06db09bbd48eaad2,PMC,Insights from Modeling the 3D Structure of New Delhi Metallo-β-Lactamse and Its Binding Interactions with Antibiotic Drugs,http://dx.doi.org/10.1371/journal.pone.0018414,PMC3073942,21494599,CC BY,"New Delhi metallo-beta-lactamase (NDM-1) is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotic drugs. This is because it can inactivate most beta-lactam antibiotic drugs by hydrolyzing them. For in-depth understanding of the hydrolysis mechanism, the three-dimensional structure of NDM-1 was developed. With such a structural frame, two enzyme-ligand complexes were derived by respectively docking Imipenem and Meropenem (two typical beta-lactam antibiotic drugs) to the NDM-1 receptor. It was revealed from the NDM-1/Imipenem complex that the antibiotic drug was hydrolyzed while sitting in a binding pocket of NDM-1 formed by nine residues. And for the case of NDM-1/Meropenem complex, the antibiotic drug was hydrolyzed in a binding pocket formed by twelve residues. All these constituent residues of the two binding pockets were explicitly defined and graphically labeled. It is anticipated that the findings reported here may provide useful insights for developing new antibiotic drugs to overcome the resistance problem.",2011 Apr 11,"['Wang, Jing-Fang', 'Chou, Kuo-Chen']",PLoS One,,,True
27548472c288a185911a8907c927d18f3c9b0abe,PMC,Production of IFN-β during Listeria monocytogenes Infection Is Restricted to Monocyte/Macrophage Lineage,http://dx.doi.org/10.1371/journal.pone.0018543,PMC3073975,21494554,CC BY,"The family of type I interferons (IFN), which consists of several IFN-α and one IFN-β, are produced not only after stimulation by viruses, but also after infection with non-viral pathogens. In the course of bacterial infections, these cytokines could be beneficial or detrimental. IFN-β is the primary member of type I IFN that initiates a cascade of IFN-α production. Here we addressed the question which cells are responsible for IFN-β expression after infection with the intracellular pathogen Listeria monocytogenes by using a genetic approach. By means of newly established reporter mice, maximum of IFN-β expression was observed at 24 hours post infection in spleen and, surprisingly, 48 hours post infection in colonized cervical and inguinal lymph nodes. Colonization of lymph nodes was independent of the type I IFN signaling, as well as bacterial dose and strain. Using cell specific reporter function and conditional deletions we could define cells expressing LysM as the major IFN-β producers, with cells formerly defined as Tip-DCs being the highest. Neutrophilic granulocytes, dendritic cells and plasmacytoid dendritic cells did not significantly contribute to type I IFN production.",2011 Apr 11,"['Solodova, Evgenia', 'Jablonska, Jadwiga', 'Weiss, Siegfried', 'Lienenklaus, Stefan']",PLoS One,,,True
21a539cc5e6c5ce8c39d80a59033791d7860a8b0,PMC,Modification of PCV-2 virulence by substitution of the genogroup motif of the capsid protein,http://dx.doi.org/10.1186/1297-9716-42-54,PMC3074528,21435235,CC BY,"Porcine circovirus type 2 (PCV-2) is the causal agent of the post-weaning multisystemic wasting syndrome (PMWS). PCV-2 are small single-stranded circular DNA viruses clustered into two main genogroups: PCV-2a and PCV-2b. Each genogroup present a specific highly-conserved motif of six amino acids (between amino acids 86 and 91) in the PCV-2 capsid protein. The aim of this study was to verify whether the motif located in the capsid protein and specific to each PCV-2 genogroup contributes to virulence. Two parental DNA clones, PCV-2a and PCV-2b, were constructed as well as two mutants DNA clones, PCV-2a/motif 2b and PCV-2b/motif 2a by exchanging the capsid motif of each genogroup. The four DNA clones were characterized in vitro as well as in vivo. Cells transfected by the four DNA clones produced infectious viruses. In specific-pathogen-free piglets transfected by the four infectious DNA clones, PCV-2b/motif 2a virulence was not attenuated while the PCV-2a/motif 2b virulence was drastically reduced compared to their parent virulence. These results suggest that the amino acids between positions 86 and 91 of the capsid protein are determinant for the virulence of isolates. However, the environment of this motif seems also involved.",2011 Mar 24,"['Allemandou, Aude', 'Grasland, Béatrice', 'Hernandez-Nignol, Anne-Cécile', ""Kéranflec'h, André"", 'Cariolet, Roland', 'Jestin, André']",Vet Res,,,True
ddf12f9e4ca7761aa1c1fd192e9bc9103ad8a642,PMC,Antigen-Specific Monoclonal Antibodies Isolated from B Cells Expressing Constitutively Active STAT5,http://dx.doi.org/10.1371/journal.pone.0017189,PMC3078118,21525985,CC BY,"BACKGROUND: Fully human monoclonal antibodies directed against specific pathogens have a high therapeutic potential, but are difficult to generate. METHODOLOGY/PRINCIPAL FINDINGS: Memory B cells were immortalized by expressing an inducible active mutant of the transcription factor Signal Transducer and Activator of Transcription 5 (STAT5). Active STAT5 inhibits the differentiation of B cells while increasing their replicative life span. We obtained cloned B cell lines, which produced antibodies in the presence of interleukin 21 after turning off STAT5. We used this method to obtain monoclonal antibodies against the model antigen tetanus toxin. CONCLUSIONS/SIGNIFICANCE: Here we describe a novel and relatively simple method of immortalizing antigen-specific human B cells for isolation of human monoclonal antibodies. These results show that STAT5 overexpression can be employed to isolate antigen specific antibodies from human memory B cells.",2011 Apr 15,"['Scheeren, Ferenc A.', 'van Geelen, Caroline M. M.', 'Yasuda, Etsuko', 'Spits, Hergen', 'Beaumont, Tim']",PLoS One,,,True
21caf0c49864b6af4c62e68e3ff7374e14c16537,PMC,Genomic Characterization and High Prevalence of Bocaviruses in Swine,http://dx.doi.org/10.1371/journal.pone.0017292,PMC3078135,21525999,CC BY,"Using random PCR amplification followed by plasmid subcloning and DNA sequencing, we detected bocavirus related sequences in 9 out of 17 porcine stool samples. Using primer walking, we sequenced the nearly complete genomes of two highly divergent bocaviruses we provisionally named porcine bocavirus 1 isolate H18 (PBoV1-H18) and porcine bocavirus 2 isolate A6 (PBoV2-A6) which differed by 51.8% in their NS1 protein. Phylogenetic analysis indicated that PBoV1-H18 was very closely related to a ∼2 Kb central region of a porcine bocavirus-like virus (PBo-LikeV) from Sweden described in 2009. PBoV2-A6 was very closely related to the porcine bocavirus genomes PBoV-1 and PBoV2 from China described in 2010. Among 340 fecal samples collected from different age, asymptomatic swine in five Chinese provinces, the prevalence of PBoV1-H18 and PBoV2-A6 related viruses were 45–75% and 55–70% respectively, with 30–47% of pigs co-infected. PBoV1-A6 related strains were highly conserved, while PBoV2-H18 related strains were more diverse, grouping into two genotypes corresponding to the previously described PBoV1 and PBoV2. Together with the recently described partial bocavirus genomes labeled V6 and V7, a total of three major porcine bocavirus clades have therefore been described to date. Further studies will be required to elucidate the possible pathogenic impact of these diverse bocaviruses either alone or in combination with other porcine viruses.",2011 Apr 15,"['Shan, Tongling', 'Lan, Daoliang', 'Li, Linlin', 'Wang, Chunmei', 'Cui, Li', 'Zhang, Wen', 'Hua, Xiuguo', 'Zhu, Caixia', 'Zhao, Wei', 'Delwart, Eric']",PLoS One,,,True
a642d4021e92bf6974af05b20f17e6e8b25c368c,PMC,Viral and Atypical Bacterial Detection in Acute Respiratory Infection in Children Under Five Years,http://dx.doi.org/10.1371/journal.pone.0018928,PMC3078930,21533115,CC BY,"BACKGROUND: Acute respiratory infection (ARI) is a leading cause of morbidity and mortality in children worldwide. This study aimed to determine the viral and atypical bacterial causes of different severities and clinical manifestations of ARI in preschool children from low-income families in North-East Brazil. METHODS: Clinical/demographic data and nasopharyngeal aspirates (NPA) were prospectively collected from children <5 years presenting with ARI over one year to a paediatric A&E department. Disease severity was grouped according to presence of lower respiratory tract signs, need for hospital admission and need for oxygen. Clinical manifestation of ARI was based on discharge diagnosis from hospital with four conditions predominating: bronchiolitis, pneumonia, episodic viral wheeze/asthma and upper respiratory tract infection. Multiplex PCR was used to detect 17 common respiratory viral and atypical bacterial pathogens in NPA. FINDINGS: 407 children with a median age of eight months were recruited. Pathogens were detected in 85·5% samples with co-infection being particularly common (39·5%). Respiratory Syncytial Virus (RSV; 37%), Adenoviruses (AdV; 25%), Rhinoviruses (hRV; 19%), Bocavirus (hBoV; 19%), human Meta-pneumovirus (hMPV; 10%) and Mycoplasma pneumoniae (Mpp; 10%) were most prevalent. Detection and co-infection rates were similar in all severities and clinical manifestations of ARI apart from RSV, which was associated with more severe disease and specifically more severe cases of bronchiolitis, and Mpp, which was associated with more severe cases of pneumonia. Mpp was detected in 17% of children admitted to hospital with pneumonia. INTERPRETATION: This study underlines the importance of viral and atypical bacterial pathogens in ARI in pre-school children and highlights the complex epidemiology of these pathogens in this age group. Generally, viruses and atypical bacteria were detected in all severities and clinical manifestations of ARI but RSV and Mpp were associated with more severe cases of bronchiolitis and pneumonia respectively.",2011 Apr 18,"['Bezerra, Patrícia G. M.', 'Britto, Murilo C. A.', 'Correia, Jailson B.', 'Duarte, Maria do Carmo M. B.', 'Fonceca, Angela M.', 'Rose, Katie', 'Hopkins, Mark J.', 'Cuevas, Luis E.', 'McNamara, Paul S.']",PLoS One,,,True
408e677725167e4c45863aab7d91de0a5dae6d22,PMC,Communicating uncertainty - how Australian television reported H1N1 risk in 2009: a content analysis,http://dx.doi.org/10.1186/1471-2458-11-181,PMC3079644,21435263,CC BY,"BACKGROUND: Health officials face particular challenges in communicating with the public about emerging infectious diseases of unknown severity such as the 2009 H1N1(swine 'flu) pandemic (pH1N1). Statements intended to create awareness and convey the seriousness of infectious disease threats can draw accusations of scare-mongering, while officials can be accused of complacency if such statements are not made. In these communication contexts, news journalists, often reliant on official sources to understand issues are pivotal in selecting and emphasising aspects of official discourse deemed sufficiently newsworthy to present to the public. This paper presents a case-study of news communication regarding the emergence of pH1N1. METHODS: We conducted a content analysis of all television news items about pH1N1. We examined news and current affairs items broadcast on 5 free-to-air Sydney television channels between April 25 2009 (the first report) and October 9 (prior to the vaccine release) for statements about [1] the seriousness of the disease [2] how the public could minimise contagion [3] government responses to emerging information. RESULTS: pH1N1 was the leading health story for eight of 24 weeks and was in the top 5 for 20 weeks. 353 news items were identified, yielding 3086 statements for analysis, with 63.4% related to the seriousness of the situation, 12.9% providing advice for viewers and 23.6% involving assurances from government. Coverage focused on infection/mortality rates, the spread of the virus, the need for public calm, the vulnerability of particular groups, direct and indirect advice for viewers, and government reassurances about effective management. CONCLUSIONS: Overall, the reporting of 2009 pH1N1 in Sydney, Australia was generally non-alarmist, while conveying that pH1N1 was potentially serious. Daily infection rate tallies and commentary on changes in the pandemic alert level were seldom contextualised to assist viewers in understanding personal relevance. Suggestions are made about how future reporting of emerging infectious diseases could be enhanced.",2011 Mar 24,"['Fogarty, Andrea S', 'Holland, Kate', 'Imison, Michelle', 'Blood, R Warwick', 'Chapman, Simon', 'Holding, Simon']",BMC Public Health,,,True
568cf52b425ceaf8d1e9a14bbd088c493e8fd4fe,PMC,Analysis of codon usage and nucleotide composition bias in polioviruses,http://dx.doi.org/10.1186/1743-422X-8-146,PMC3079669,21450075,CC BY,"BACKGROUND: Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and a member of the family of Picornaviridae and among the most rapidly evolving viruses known. Analysis of codon usage can reveal much about the molecular evolution of the viruses. However, little information about synonymous codon usage pattern of polioviruses genome has been acquired to date. METHODS: The relative synonymous codon usage (RSCU) values, effective number of codon (ENC) values, nucleotide contents and dinucleotides were investigated and a comparative analysis of codon usage pattern for open reading frames (ORFs) among 48 polioviruses isolates including 31 of genotype 1, 13 of genotype 2 and 4 of genotype 3. RESULTS: The result shows that the overall extent of codon usage bias in poliovirus samples is low (mean ENC = 53.754 > 40). The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in those polioviruses. Depending on the RSCU data, it was found that there was a significant variation in bias of codon usage among three genotypes. Geographic factor also has some effect on the codon usage pattern (exists in the genotype-1 of polioviruses). No significant effect in gene length or vaccine derived polioviruses (DVPVs), wild viruses and live attenuated virus was observed on the variations of synonymous codon usage in the virus genes. The relative abundance of dinucleotide (CpG) in the ORFs of polioviruses are far below expected values especially in DVPVs and attenuated virus of polioviruses genotype 1. CONCLUSION: The information from this study may not only have theoretical value in understanding poliovirus evolution, especially for DVPVs genotype 1, but also have potential value for the development of poliovirus vaccines.",2011 Mar 30,"['Zhang, Jie', 'Wang, Meng', 'Liu, Wen-qian', 'Zhou, Jian-hua', 'Chen, Hao-tai', 'Ma, Li-na', 'Ding, Yao-zhong', 'Gu, Yuan-xing', 'Liu, Yong-sheng']",Virol J,,,True
5d2c1aaad487ae9b76099721947c8948a57ebba3,PMC,Comparative Pathogenesis of Three Human and Zoonotic SARS-CoV Strains in Cynomolgus Macaques,http://dx.doi.org/10.1371/journal.pone.0018558,PMC3080360,21533129,CC BY,"The severe acute respiratory syndrome (SARS) epidemic was characterized by increased pathogenicity in the elderly due to an early exacerbated innate host response. SARS-CoV is a zoonotic pathogen that entered the human population through an intermediate host like the palm civet. To prevent future introductions of zoonotic SARS-CoV strains and subsequent transmission into the human population, heterologous disease models are needed to test the efficacy of vaccines and therapeutics against both late human and zoonotic isolates. Here we show that both human and zoonotic SARS-CoV strains can infect cynomolgus macaques and resulted in radiological as well as histopathological changes similar to those seen in mild human cases. Viral replication was higher in animals infected with a late human phase isolate compared to a zoonotic isolate. While there were significant differences in the number of host genes differentially regulated during the host responses between the three SARS-CoV strains, the top pathways and functions were similar and only apparent early during infection with the majority of genes associated with interferon signaling pathways. This study characterizes critical disease models in the evaluation and licensure of therapeutic strategies against SARS-CoV for human use.",2011 Apr 20,"['Rockx, Barry', 'Feldmann, Friederike', 'Brining, Douglas', 'Gardner, Don', 'LaCasse, Rachel', 'Kercher, Lisa', 'Long, Dan', 'Rosenke, Rebecca', 'Virtaneva, Kimmo', 'Sturdevant, Daniel E.', 'Porcella, Stephen F.', 'Mattoon, John', 'Parnell, Michael', 'Baric, Ralph S.', 'Feldmann, Heinz']",PLoS One,,,True
f5f53c6d9a31095c447315d0c2ebc42cbcebcfd2,PMC,Altering α-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism,http://dx.doi.org/10.1186/1479-0556-9-8,PMC3080791,21477292,CC BY,"BACKGROUND: The envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV) can efficiently pseudotype lentiviral vectors. Some strains of LCMV exploit high affinity interactions with α-dystroglycan (α-DG) to bind to cell surfaces and subsequently fuse in low pH endosomes. LCMV strains with low α-DG affinity utilize an unknown receptor and display unique tissue tropisms. We pseudotyped non-primate feline immunodeficiency virus (FIV) vectors using LCMV derived glycoproteins with high or low affinity to α-DG and evaluated their properties in vitro and in vivo. METHODS: We pseudotyped FIV with the LCMV WE54 strain envelope glycoprotein and also engineered a point mutation in the WE54 envelope glycoprotein (L260F) to diminish α-DG affinity and direct binding to alternate receptors. We hypothesized that this change would alter in vivo tissue tropism and enhance gene transfer to neonatal animals. RESULTS: In mice, hepatic α- and β-DG expression was greatest at the late gestational and neonatal time points. When displayed on the surface of the FIV lentivirus the WE54 L260F mutant glycoprotein bound weakly to immobilized α-DG. Additionally, LCMV WE54 pseudotyped FIV vector transduction was neutralized by pre-incubation with soluble α-DG, while the mutant glycoprotein pseudotyped vector was not. In vivo gene transfer in adult mice with either envelope yielded low transduction efficiencies in hepatocytes following intravenous delivery. In marked contrast, neonatal gene transfer with the LCMV envelopes, and notably with the FIV-L260F vector, conferred abundant liver and lower level cardiomyocyte transduction as detected by luciferase assays, bioluminescent imaging, and β-galactosidase staining. CONCLUSIONS: These results suggest that a developmentally regulated receptor for LCMV is expressed abundantly in neonatal mice. LCMV pseudotyped vectors may have applications for neonatal gene transfer. ABBREVIATIONS: Armstrong 53b (Arm53b); baculovirus Autographa californica GP64 (GP64); charge-coupled device (CCD); dystroglycan (DG); feline immunodeficiency virus (FIV); glycoprotein precursor (GP-C); firefly luciferase (Luc); lymphocytic choriomeningitis virus (LCMV); nuclear targeted β-galactosidase (ntLacZ); optical density (OD); PBS/0.1% (w/v) Tween-20 (PBST); relative light units (RLU); Rous sarcoma virus (RSV); transducing units per milliliter (TU/ml); vesicular stomatitis virus (VSV-G); wheat germ agglutinin (WGA); 50% reduction in binding (C(50)).",2011 Apr 8,"['Dylla, Douglas E', 'Xie, Litao', 'Michele, Daniel E', 'Kunz, Stefan', 'McCray, Paul B']",Genet Vaccines Ther,,,True
b3574701bdaf6c4d408e9abe2d4176e058fc5208,PMC,"Size-Segregated Particle Number Concentrations and Respiratory Emergency Room Visits in Beijing, China",http://dx.doi.org/10.1289/ehp.1002203,PMC3080933,21118783,CC0,"BACKGROUND: The link between concentrations of particulate matter (PM) and respiratory morbidity has been investigated in numerous studies. OBJECTIVES: The aim of this study was to analyze the role of different particle size fractions with respect to respiratory health in Beijing, China. METHODS: Data on particle size distributions from 3 nm to 1 μm; PM(10) (PM ≤ 10 μm), nitrogen dioxide (NO(2)), and sulfur dioxide concentrations; and meteorologic variables were collected daily from March 2004 to December 2006. Concurrently, daily counts of emergency room visits (ERV) for respiratory diseases were obtained from the Peking University Third Hospital. We estimated pollutant effects in single- and two-pollutant generalized additive models, controlling for meteorologic and other time-varying covariates. Time-delayed associations were estimated using polynomial distributed lag, cumulative effects, and single lag models. RESULTS: Associations of respiratory ERV with NO(2) concentrations and 100–1,000 nm particle number or surface area concentrations were of similar magnitude—that is, approximately 5% increase in respiratory ERV with an interquartile range increase in air pollution concentration. In general, particles < 50 nm were not positively associated with ERV, whereas particles 50–100 nm were adversely associated with respiratory ERV, both being fractions of ultrafine particles. Effect estimates from two-pollutant models were most consistent for NO(2). CONCLUSIONS: Present levels of air pollution in Beijing were adversely associated with respiratory ERV. NO(2) concentrations seemed to be a better surrogate for evaluating overall respiratory health effects of ambient air pollution than PM(10) or particle number concentrations in Beijing.",2011 Apr 30,"['Leitte, Arne Marian', 'Schlink, Uwe', 'Herbarth, Olf', 'Wiedensohler, Alfred', 'Pan, Xiao-Chuan', 'Hu, Min', 'Richter, Matthia', 'Wehner, Birgit', 'Tuch, Thomas', 'Wu, Zhijun', 'Yang, Minjuan', 'Liu, Liqun', 'Breitner, Susanne', 'Cyrys, Josef', 'Peters, Annette', 'Wichmann, H.-Erich', 'Franck, Ulrich']",Environ Health Perspect,,,True
91312e3e01c328ebc4c8007586a84e8cfbdf45e9,PMC,"Novel, Divergent Simian Hemorrhagic Fever Viruses in a Wild Ugandan Red Colobus Monkey Discovered Using Direct Pyrosequencing",http://dx.doi.org/10.1371/journal.pone.0019056,PMC3081318,21544192,CC BY,"BACKGROUND: Simian hemorrhagic fever virus (SHFV) has caused lethal outbreaks of hemorrhagic disease in captive primates, but its distribution in wild primates has remained obscure. Here, we describe the discovery and genetic characterization by direct pyrosequencing of two novel, divergent SHFV variants co-infecting a single male red colobus monkey from Kibale National Park, Uganda. METHODOLOGY/PRINCIPAL FINDINGS: The viruses were detected directly from blood plasma using pyrosequencing, without prior virus isolation and with minimal PCR amplification. The two new SHFV variants, SHFV-krc1 and SHFV-krc2 are highly divergent from each other (51.9% nucleotide sequence identity) and from the SHFV type strain LVR 42-0/M6941 (52.0% and 51.8% nucleotide sequence identity, respectively) and demonstrate greater phylogenetic diversity within SHFV than has been documented within any other arterivirus. Both new variants nevertheless have the same 3′ genomic architecture as the type strain, containing three open reading frames not present in the other arteriviruses. CONCLUSIONS/SIGNIFICANCE: These results represent the first documentation of SHFV in a wild primate and confirm the unusual 3′ genetic architecture of SHFV relative to the other arteriviruses. They also demonstrate a degree of evolutionary divergence within SHFV that is roughly equivalent to the degree of divergence between other arterivirus species. The presence of two such highly divergent SHFV variants co-infecting a single individual represents a degree of within-host viral diversity that exceeds what has previously been reported for any arterivirus. These results expand our knowledge of the natural history and diversity of the arteriviruses and underscore the importance of wild primates as reservoirs for novel pathogens.",2011 Apr 22,"['Lauck, Michael', 'Hyeroba, David', 'Tumukunde, Alex', 'Weny, Geoffrey', 'Lank, Simon M.', 'Chapman, Colin A.', ""O'Connor, David H."", 'Friedrich, Thomas C.', 'Goldberg, Tony L.']",PLoS One,,,True
1b92fda04723ae9d30a58f10b054cc1b7971e870,PMC,CD4-Independent Human Immunodeficiency Virus Infection Involves Participation of Endocytosis and Cathepsin B,http://dx.doi.org/10.1371/journal.pone.0019352,PMC3081840,21541353,CC BY,"During a comparison of the infectivity of mNDK, a CD4-independent human immunodeficiency virus type 1 (HIV-1) strain, to various cell lines, we found that HeLa cells were much less susceptible than 293T and TE671 cells. Hybridoma cells between HeLa and 293T cells were as susceptible as 293T cells, suggesting that cellular factors enhance the mNDK infection in 293T cells. By screening a cDNA expression library in HeLa cells, cystatin C was isolated as an enhancer of the mNDK infection. Because cathepsin B protease, a natural ligand of cystatin C, was upregulated in HeLa cells, we speculated that the high levels of cathepsin B activities were inhibitory to the CD4-independent infection and that cystatin C enhanced the infection by impairing the excessive cathepsin B activity. Consistent with this idea, pretreatment of HeLa cells with 125 µM of CA-074Me, a cathepsin B inhibitor, resulted in an 8-fold enhancement of the mNDK infectivity. Because cathepsin B is activated by low pH in acidic endosomes, we further examined the potential roles of endosomes in the CD4-independent infection. Suppression of endosome acidification or endocytosis by inhibitors or by an Eps15 dominant negative mutant reduced the infectivity of mNDK in which CD4-dependent infections were not significantly impaired. Taken together, these results suggest that endocytosis, endosomal acidification, and cathepsin B activity are involved in the CD4-independent entry of HIV-1.",2011 Apr 25,"['Yoshii, Hiroaki', 'Kamiyama, Haruka', 'Goto, Kensuke', 'Oishi, Kazunori', 'Katunuma, Nobuhiko', 'Tanaka, Yuetsu', 'Hayashi, Hideki', 'Matsuyama, Toshifumi', 'Sato, Hironori', 'Yamamoto, Naoki', 'Kubo, Yoshinao']",PLoS One,,,True
0baa7fbb346a50319eb57a4a1556c3f48938d0e6,PMC,Live Bird Markets of Bangladesh: H9N2 Viruses and the Near Absence of Highly Pathogenic H5N1 Influenza,http://dx.doi.org/10.1371/journal.pone.0019311,PMC3082571,21541296,CC BY,"Avian influenza surveillance in Bangladesh has been passive, relying on poultry farmers to report suspected outbreaks of highly pathogenic H5N1 influenza. Here, the results of an active surveillance effort focusing on the live-bird markets are presented. Prevalence of influenza infection in the birds of the live bird markets is 23.0%, which is similar to that in poultry markets in other countries. Nearly all of the isolates (94%) were of the non-pathogenic H9N2 subtype, but viruses of the H1N2, H1N3, H3N6, H4N2, H5N1, and H10N7 subtypes were also observed. The highly pathogenic H5N1-subtype virus was observed at extremely low prevalence in the surveillance samples (0.08%), and we suggest that the current risk of infection for humans in the retail poultry markets in Bangladesh is negligible. However, the high prevalence of the H9 subtype and its potential for interaction with the highly pathogenic H5N1-subtype, i.e., reassortment and attenuation of host morbidity, highlight the importance of active surveillance of the poultry markets.",2011 Apr 26,"['Negovetich, Nicholas J.', 'Feeroz, Mohammed M.', 'Jones-Engel, Lisa', 'Walker, David', 'Alam, S. M. Rabiul', 'Hasan, Kamrul', 'Seiler, Patrick', 'Ferguson, Angie', 'Friedman, Kim', 'Barman, Subrata', 'Franks, John', 'Turner, Jasmine', 'Krauss, Scott', 'Webby, Richard J.', 'Webster, Robert G.']",PLoS One,,,True
47b84b720b0601da21090660ed223b7cfa1150cb,PMC,Monitoring Influenza Activity in the United States: A Comparison of Traditional Surveillance Systems with Google Flu Trends,http://dx.doi.org/10.1371/journal.pone.0018687,PMC3083406,21556151,CC0,"BACKGROUND: Google Flu Trends was developed to estimate US influenza-like illness (ILI) rates from internet searches; however ILI does not necessarily correlate with actual influenza virus infections. METHODS AND FINDINGS: Influenza activity data from 2003–04 through 2007–08 were obtained from three US surveillance systems: Google Flu Trends, CDC Outpatient ILI Surveillance Network (CDC ILI Surveillance), and US Influenza Virologic Surveillance System (CDC Virus Surveillance). Pearson's correlation coefficients with 95% confidence intervals (95% CI) were calculated to compare surveillance data. An analysis was performed to investigate outlier observations and determine the extent to which they affected the correlations between surveillance data. Pearson's correlation coefficient describing Google Flu Trends and CDC Virus Surveillance over the study period was 0.72 (95% CI: 0.64, 0.79). The correlation between CDC ILI Surveillance and CDC Virus Surveillance over the same period was 0.85 (95% CI: 0.81, 0.89). Most of the outlier observations in both comparisons were from the 2003–04 influenza season. Exclusion of the outlier observations did not substantially improve the correlation between Google Flu Trends and CDC Virus Surveillance (0.82; 95% CI: 0.76, 0.87) or CDC ILI Surveillance and CDC Virus Surveillance (0.86; 95%CI: 0.82, 0.90). CONCLUSIONS: This analysis demonstrates that while Google Flu Trends is highly correlated with rates of ILI, it has a lower correlation with surveillance for laboratory-confirmed influenza. Most of the outlier observations occurred during the 2003–04 influenza season that was characterized by early and intense influenza activity, which potentially altered health care seeking behavior, physician testing practices, and internet search behavior.",2011 Apr 27,"['Ortiz, Justin R.', 'Zhou, Hong', 'Shay, David K.', 'Neuzil, Kathleen M.', 'Fowlkes, Ashley L.', 'Goss, Christopher H.']",PLoS One,,,True
49f01042ee1df642748c8b65f2abde687b2750ed,PMC,Antioxidant Status and Immune Activity of Glycyrrhizin in Allergic Rhinitis Mice,http://dx.doi.org/10.3390/ijms12020905,PMC3083680,21541033,CC BY,"Oxidative stress is considered as a major risk factor that contributes to increased lipid peroxidation and declined antioxidants in some degenerative diseases. Glycyrrhizin is widely used to cure allergic diseases due to its medicinal properties. In the present study, we evaluated the role of glycyrrhizin on lipid peroxidation and antioxidant status in the blood and nasal mucosa of allergic rhinitis (AR) mice. Mice were divided into six groups: normal control mice, model control (MC) mice, three glycyrrhizin-treated mice groups and lycopene-treated mice. Sensitization-associated increase in lipid peroxidation was observed in the blood and nasal mucosa of MC mice. Activities of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), total antioxidant capacity (TAOC) and levels of glutathione (GSH) were found to be significantly decreased in the blood and nasal mucosa in MC mice when compared to normal control mice. However, normalized lipid peroxidation and antioxidant defenses were reported in the glycyrrhizin-treated and lycopene-treated mice. Moreover, glycyrrhizin treatment still enhanced IFN-γ and reduced IL-4 levels in glycyrrhizin-treated mice. These findings demonstrated that glycyrrhizin treatment enhanced the antioxidant status and decreased the incidence of free radical-induced lipid peroxidation and improved immunity activities in the blood and nasal mucosa of AR mice.",2011 Jan 26,"['Li, Xiao-Lan', 'Zhou, Ai-Guo', 'Zhang, Li', 'Chen, Wei-Jun']",Int J Mol Sci,,,True
b3fe63ea9f4794d58f37083f3430c6e5238449c3,PMC,Evaluation of a Novel Non-Penetrating Electrode for Use in DNA Vaccination,http://dx.doi.org/10.1371/journal.pone.0019181,PMC3084774,21559474,CC BY,"Current progress in the development of vaccines has decreased the incidence of fatal and non-fatal infections and increased longevity. However, new technologies need to be developed to combat an emerging generation of infectious diseases. DNA vaccination has been demonstrated to have great potential for use with a wide variety of diseases. Alone, this technology does not generate a significant immune response for vaccination, but combined with delivery by electroporation (EP), can enhance plasmid expression and immunity. Most EP systems, while effective, can be invasive and painful making them less desirable for use in vaccination. Our lab recently developed a non-invasive electrode known as the multi-electrode array (MEA), which lies flat on the surface of the skin without penetrating the tissue. In this study we evaluated the MEA for its use in DNA vaccination using Hepatitis B virus as the infectious model. We utilized the guinea pig model because their skin is similar in thickness and morphology to humans. The plasmid encoding Hepatitis B surface antigen (HBsAg) was delivered intradermally with the MEA to guinea pig skin. The results show increased protein expression resulting from plasmid delivery using the MEA as compared to injection alone. Within 48 hours of treatment, there was an influx of cellular infiltrate in experimental groups. Humoral responses were also increased significantly in both duration and intensity as compared to injection only groups. While this electrode requires further study, our results suggest that the MEA has potential for use in electrically mediated intradermal DNA vaccination.",2011 Apr 29,"['Donate, Amy', 'Coppola, Domenico', 'Cruz, Yolmari', 'Heller, Richard']",PLoS One,,,True
0c04a2b5c4c91d76c26736dd05ce6fc6385cc167,PMC,LILRA3 Binds Both Classical and Non-Classical HLA Class I Molecules but with Reduced Affinities Compared to LILRB1/LILRB2: Structural Evidence,http://dx.doi.org/10.1371/journal.pone.0019245,PMC3084784,21559424,CC BY,"Structurally, Group 1 LILR (Leukocyte Immunogloblin (Ig)-Like Receptor, also known as Ig-like transcripts, ILT; Leukocyte Ig-like receptor, LIR; and CD85) members are very similar in terms of the HLAIs (human leukocyte antigen class I molecules) binding region and were hypothesized that they all bind to HLAIs. As one of the Group 1 LILRs, LILRA3 is the only secretory LILR and may greatly control the inhibitory immune response induced by LILRB1, LILRB2, and other HLA-binding LILR molecules like LILRA1. Nevertheless, little was known about the binding of LILRA3 to HLAIs. In this report, we present the crystal structure of the LILRA3 domain 1 (D1) and evaluate the D1 and D1D2 (domain 1 and domain 2) binding to classical and non-classical HLAIs using BIAcore® surface plasmon resonance analysis (SPR). We found that LILRA3 binds both classical HLA-A*0201 and non-classical HLA-G1 but with reduced affinities compared to either LILRB1 or LILRB2. The polymorphic amino acids and the LILRA3 D1 structure support this notion.",2011 Apr 29,"['Ryu, Myongchol', 'Chen, Yong', 'Qi, Jianxun', 'Liu, Jun', 'Fan, Zheng', 'Nam, Gol', 'Shi, Yi', 'Cheng, Hao', 'Gao, George F.']",PLoS One,,,True
2c468e84bbaa10edb38eb112ab8088e74073c02f,PMC,Monitoring the Systemic Human Memory B Cell Compartment of Melanoma Patients for Anti-Tumor IgG Antibodies,http://dx.doi.org/10.1371/journal.pone.0019330,PMC3084832,21559411,CC BY,"Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10) to primary and metastatic melanoma cells compared to healthy volunteers (n = 10) (P<0.0001). Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21) (P<0.0001). Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800) compared to 2% of cultures from healthy controls (n = 600) produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer.",2011 Apr 29,"['Gilbert, Amy E.', 'Karagiannis, Panagiotis', 'Dodev, Tihomir', 'Koers, Alexander', 'Lacy, Katie', 'Josephs, Debra H.', 'Takhar, Pooja', 'Geh, Jenny L. C.', 'Healy, Ciaran', 'Harries, Mark', 'Acland, Katharine M.', 'Rudman, Sarah M.', 'Beavil, Rebecca L.', 'Blower, Philip J.', 'Beavil, Andrew J.', 'Gould, Hannah J.', 'Spicer, James', 'Nestle, Frank O.', 'Karagiannis, Sophia N.']",PLoS One,,,True
cfffac30aa716974333312a44475097d94c8f475,PMC,Visualizing Clinical Evidence: Citation Networks for the Incubation Periods of Respiratory Viral Infections,http://dx.doi.org/10.1371/journal.pone.0019496,PMC3084881,21559339,CC BY,"Simply by repetition, medical facts can become enshrined as truth even when there is little empirical evidence supporting them. We present an intuitive and clear visual design for tracking the citation history of a particular scientific fact over time. We apply this method to data from a previously published literature review on the incubation period of nine respiratory viral infections. The resulting citation networks reveal that the conventional wisdom about the incubation period for these diseases was based on a small fraction of available data and in one case, on no retrievable empirical evidence. Overall, 50% of all incubation period statements did not provide a source for their estimate and 65% of original sources for incubation period data were not incorporated into subsequent publications. More standardized and widely available methods for visualizing these histories of medical evidence are needed to ensure that conventional wisdom cannot stray too far from empirically supported knowledge.",2011 Apr 29,"['Reich, Nicholas G.', 'Perl, Trish M.', 'Cummings, Derek A. T.', 'Lessler, Justin']",PLoS One,,,True
7d84b116132df661fef2f697880e3856e1e4ca8a,PMC,Visualizing Clinical Evidence: Citation Networks for the Incubation Periods of Respiratory Viral Infections,http://dx.doi.org/10.1371/journal.pone.0019496,PMC3084881,21559339,CC BY,"Simply by repetition, medical facts can become enshrined as truth even when there is little empirical evidence supporting them. We present an intuitive and clear visual design for tracking the citation history of a particular scientific fact over time. We apply this method to data from a previously published literature review on the incubation period of nine respiratory viral infections. The resulting citation networks reveal that the conventional wisdom about the incubation period for these diseases was based on a small fraction of available data and in one case, on no retrievable empirical evidence. Overall, 50% of all incubation period statements did not provide a source for their estimate and 65% of original sources for incubation period data were not incorporated into subsequent publications. More standardized and widely available methods for visualizing these histories of medical evidence are needed to ensure that conventional wisdom cannot stray too far from empirically supported knowledge.",2011 Apr 29,"['Reich, Nicholas G.', 'Perl, Trish M.', 'Cummings, Derek A. T.', 'Lessler, Justin']",PLoS One,,,True
21e6d4c42e4375fcb05eeebb140a805461688542,PMC,Visualizing Clinical Evidence: Citation Networks for the Incubation Periods of Respiratory Viral Infections,http://dx.doi.org/10.1371/journal.pone.0019496,PMC3084881,21559339,CC BY,"Simply by repetition, medical facts can become enshrined as truth even when there is little empirical evidence supporting them. We present an intuitive and clear visual design for tracking the citation history of a particular scientific fact over time. We apply this method to data from a previously published literature review on the incubation period of nine respiratory viral infections. The resulting citation networks reveal that the conventional wisdom about the incubation period for these diseases was based on a small fraction of available data and in one case, on no retrievable empirical evidence. Overall, 50% of all incubation period statements did not provide a source for their estimate and 65% of original sources for incubation period data were not incorporated into subsequent publications. More standardized and widely available methods for visualizing these histories of medical evidence are needed to ensure that conventional wisdom cannot stray too far from empirically supported knowledge.",2011 Apr 29,"['Reich, Nicholas G.', 'Perl, Trish M.', 'Cummings, Derek A. T.', 'Lessler, Justin']",PLoS One,,,True
d04d63e56673f57ed326ebf2314e5b8192266a79,PMC,Transmission Potential of Chikungunya Virus and Control Measures: The Case of Italy,http://dx.doi.org/10.1371/journal.pone.0018860,PMC3086881,21559329,CC BY,"During summer 2007 Italy has experienced an epidemic caused by Chikungunya virus – the first large outbreak documented in a temperate climate country – with approximately 161 laboratory confirmed cases concentrated in two bordering villages in North–Eastern Italy comprising 3,968 inhabitants. The seroprevalence was recently estimated to be 10.2%. In this work we provide estimates of the transmission potential of the virus and we assess the efficacy of the measures undertaken by public health authorities to control the epidemic spread. To such aim, we developed a model describing the temporal dynamics of the competent vector, known as Aedes albopictus, explicitly depending on climatic factors, coupled to an epidemic transmission model describing the spread of the epidemic in both humans and mosquitoes. The cumulative number of notified cases predicted by the model was 185 on average (95% CI 117–278), in good agreement with observed data. The probability of observing a major outbreak after the introduction of an infective human case was estimated to be in the range of 32%–76%. We found that the basic reproduction number was in the range of 1.8–6 but it could have been even larger, depending on the density of mosquitoes, which in turn depends on seasonal meteorological effects, besides other local abiotic factors. These results confirm the increasing risk of tropical vector–borne diseases in temperate climate countries, as a consequence of globalization. However, our results show that an epidemic can be controlled by performing a timely intervention, even if the transmission potential of Chikungunya virus is sensibly high.",2011 May 3,"['Poletti, Piero', 'Messeri, Gianni', 'Ajelli, Marco', 'Vallorani, Roberto', 'Rizzo, Caterina', 'Merler, Stefano']",PLoS One,,,True
438e817dea190348df99e09a8e519fc64101b899,PMC,Analysis of synonymous codon usage in Hepatitis A virus,http://dx.doi.org/10.1186/1743-422X-8-174,PMC3087699,21496278,CC BY,"BACKGROUND: Hepatitis A virus is the causative agent of type A viral hepatitis, which causes occasional acute hepatitis. Nevertheless, little information about synonymous codon usage pattern of HAV genome in the process of its evolution is available. In this study, the key genetic determinants of codon usage in HAV were examined. RESULTS: The overall extent of codon usage bias in HAV is high in Picornaviridae. And the patterns of synonymous codon usage are quite different in HAV genomes from different location. The base composition is closely correlated with codon usage bias. Furthermore, the most important determinant that results in such a high codon bias in HAV is mutation pressure rather than natural selection. CONCLUSIONS: HAV presents a higher codon usage bias than other members of Picornaviridae. Compositional constraint is a significant element that influences the variation of synonymous codon usage in HAV genome. Besides, mutation pressure is supposed to be the major factor shaping the hyperendemic codon usage pattern of HAV.",2011 Apr 16,"['Zhang, Yiqiang', 'Liu, Yongsheng', 'Liu, Wenqian', 'Zhou, Jianhua', 'Chen, Haotai', 'Wang, Yin', 'Ma, Lina', 'Ding, Yaozhong', 'Zhang, Jie']",Virol J,,,True
96ba8069882d695675b9e2e6d32c3640910735b4,PMC,Clustering Heart Rate Dynamics Is Associated with β-Adrenergic Receptor Polymorphisms: Analysis by Information-Based Similarity Index,http://dx.doi.org/10.1371/journal.pone.0019232,PMC3087751,21573230,CC BY,"BACKGROUND: Genetic polymorphisms in the gene encoding the β-adrenergic receptors (β-AR) have a pivotal role in the functions of the autonomic nervous system. Using heart rate variability (HRV) as an indicator of autonomic function, we present a bottom-up genotype–phenotype analysis to investigate the association between β-AR gene polymorphisms and heart rate dynamics. METHODS: A total of 221 healthy Han Chinese adults (59 males and 162 females, aged 33.6±10.8 years, range 19 to 63 years) were recruited and genotyped for three common β-AR polymorphisms: β(1)-AR Ser49Gly, β(2)-AR Arg16Gly and β(2)-AR Gln27Glu. Each subject underwent two hours of electrocardiogram monitoring at rest. We applied an information-based similarity (IBS) index to measure the pairwise dissimilarity of heart rate dynamics among study subjects. RESULTS: With the aid of agglomerative hierarchical cluster analysis, we categorized subjects into major clusters, which were found to have significantly different distributions of β(2)-AR Arg16Gly genotype. Furthermore, the non-randomness index, a nonlinear HRV measure derived from the IBS method, was significantly lower in Arg16 homozygotes than in Gly16 carriers. The non-randomness index was negatively correlated with parasympathetic-related HRV variables and positively correlated with those HRV indices reflecting a sympathovagal shift toward sympathetic activity. CONCLUSIONS: We demonstrate a bottom-up categorization approach combining the IBS method and hierarchical cluster analysis to detect subgroups of subjects with HRV phenotypes associated with β-AR polymorphisms. Our results provide evidence that β(2)-AR polymorphisms are significantly associated with the acceleration/deceleration pattern of heart rate oscillation, reflecting the underlying mode of autonomic nervous system control.",2011 May 4,"['Yang, Albert C.', 'Tsai, Shih-Jen', 'Hong, Chen-Jee', 'Wang, Cynthia', 'Chen, Tai-Jui', 'Liou, Ying-Jay', 'Peng, Chung-Kang']",PLoS One,,,True
822233763421a1e054abbc49c00a8726cb3ebfe1,PMC,Distribution of the Phenotypic Effects of Random Homologous Recombination between Two Virus Species,http://dx.doi.org/10.1371/journal.ppat.1002028,PMC3088723,21573141,CC BY,"Recombination has an evident impact on virus evolution and emergence of new pathotypes, and has generated an immense literature. However, the distribution of phenotypic effects caused by genome-wide random homologous recombination has never been formally investigated. Previous data on the subject have promoted the implicit view that most viral recombinant genomes are likely to be deleterious or lethal if the nucleotide identity of parental sequences is below 90%. We decided to challenge this view by creating a bank of near-random recombinants between two viral species of the genus Begomovirus (Family Geminiviridae) exhibiting 82% nucleotide identity, and by testing infectivity and in planta accumulation of recombinant clones randomly extracted from this bank. The bank was created by DNA-shuffling—a technology initially applied to the random shuffling of individual genes, and here implemented for the first time to shuffle full-length viral genomes. Together with our previously described system allowing the direct cloning of full-length infectious geminivirus genomes, it provided a unique opportunity to generate hundreds of “mosaic” virus genomes, directly testable for infectivity. A subset of 47 randomly chosen recombinants was sequenced, individually inoculated into tomato plants, and compared with the parental viruses. Surprisingly, our results showed that all recombinants were infectious and accumulated at levels comparable or intermediate to that of the parental clones. This indicates that, in our experimental system, despite the fact that the parental genomes differ by nearly 20%, lethal and/or large deleterious effects of recombination are very rare, in striking contrast to the common view that has emerged from previous studies published on other viruses.",2011 May 5,"['Vuillaume, Florence', 'Thébaud, Gaël', 'Urbino, Cica', 'Forfert, Nadège', 'Granier, Martine', 'Froissart, Rémy', 'Blanc, Stéphane', 'Peterschmitt, Michel']",PLoS Pathog,,,True
82448eac471a17fd751603f9b91450b6961d3a0e,PMC,Action Mechanisms of Lithium Chloride on Cell Infection by Transmissible Gastroenteritis Coronavirus,http://dx.doi.org/10.1371/journal.pone.0018669,PMC3089605,21573100,CC BY,"Transmissible gastroenteritis virus (TGEV) is a porcine coronavirus. Lithium chloride (LiCl) has been found to be effective against several DNA viruses, such as Herpes simplex virus and vaccinia virus. Recently, we and others have reported the inhibitory effect of LiCl on avian infectious bronchitis coronavirus (IBV) infection, an RNA virus. In the current study, the action mechanism of LiCl on cell infection by TGEV was investigated. Plaque assays and 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenyl tetrazoliumbromide (MTT) assays showed that the cell infection by TGEV was inhibited in a dose-dependent manner, when LiCl was added to virus-infected cells; the cell infection was not affected when either cells or viruses were pretreated with the drug. The inhibition of TGEV infection in vitro by LiCl was observed at different virus doses and with different cell lines. The inhibitory effect of LiCl against TGEV infection and transcription was confirmed by RT-PCR and real-time PCR targeting viral S and 3CL-protease genes. The time-of-addition effect of the drug on TGEV infection indicated that LiCl acted on the initial and late stage of TGEV infection. The production of virus was not detected at 36 h post-infection due to the drug treatment. Moreover, immunofluorescence (IF) and flow cytometry analyses based on staining of Annexin V and propidium iodide staining of nuclei indicated that early and late cell apoptosis induced by TGEV was inhibited efficiently. The ability of LiCl to inhibit apoptosis was investigated by IF analysis of caspase-3 expression. Our data indicate that LiCl inhibits TGEV infection by exerting an anti-apoptotic effect. The inhibitory effect of LiCl was also observed with porcine epidemic diarrhea coronavirus. Together with other reports concerning the inhibitory effect of lithium salts on IBV in cell culture, our results indicate that LiCl may be a potent agent against porcine and avian coronaviruses.",2011 May 6,"['Ren, Xiaofeng', 'Meng, Fandan', 'Yin, Jiechao', 'Li, Guangxing', 'Li, Xunliang', 'Wang, Chao', 'Herrler, Georg']",PLoS One,,,True
aae339db3ebacca2632136e51dac48f209a952f6,PMC,The Infection of Chicken Tracheal Epithelial Cells with a H6N1 Avian Influenza Virus,http://dx.doi.org/10.1371/journal.pone.0018894,PMC3089607,21573102,CC BY,"Sialic acids (SAs) linked to galactose (Gal) in α2,3- and α2,6-configurations are the receptors for avian and human influenza viruses, respectively. We demonstrate that chicken tracheal ciliated cells express α2,3-linked SA, while goblet cells mainly express α2,6-linked SA. In addition, the plant lectin MAL-II, but not MAA/MAL-I, is bound to the surface of goblet cells, suggesting that SA2,3-linked oligosaccharides with Galβ1–3GalNAc subterminal residues are specifically present on the goblet cells. Moreover, both α2,3- and α2,6-linked SAs are detected on single tracheal basal cells. At a low multiplicity of infection (MOI) avian influenza virus H6N1 is exclusively detected in the ciliated cells, suggesting that the ciliated cell is the major target cell of the H6N1 virus. At a MOI of 1, ciliated, goblet and basal cells are all permissive to the AIV infection. This result clearly elucidates the receptor distribution for the avian influenza virus among chicken tracheal epithelial cells and illustrates a primary cell model for evaluating the cell tropisms of respiratory viruses in poultry.",2011 May 6,"['Shen, Ching-I', 'Wang, Ching-Ho', 'Shen, Shih-Cheng', 'Lee, Hsiu-Chin', 'Liao, Jiunn-Wang', 'Su, Hong-Lin']",PLoS One,,,True
01c25f9838ef8e005bf720c4f76e67a9f1038ff0,PMC,Classification of viral zoonosis through receptor pattern analysis,http://dx.doi.org/10.1186/1471-2105-12-96,PMC3090355,21489240,CC BY,"BACKGROUND: Viral zoonosis, the transmission of a virus from its primary vertebrate reservoir species to humans, requires ubiquitous cellular proteins known as receptor proteins. Zoonosis can occur not only through direct transmission from vertebrates to humans, but also through intermediate reservoirs or other environmental factors. Viruses can be categorized according to genotype (ssDNA, dsDNA, ssRNA and dsRNA viruses). Among them, the RNA viruses exhibit particularly high mutation rates and are especially problematic for this reason. Most zoonotic viruses are RNA viruses that change their envelope proteins to facilitate binding to various receptors of host species. In this study, we sought to predict zoonotic propensity through the analysis of receptor characteristics. We hypothesized that the major barrier to interspecies virus transmission is that receptor sequences vary among species--in other words, that the specific amino acid sequence of the receptor determines the ability of the viral envelope protein to attach to the cell. RESULTS: We analysed host-cell receptor sequences for their hydrophobicity/hydrophilicity characteristics. We then analysed these properties for similarities among receptors of different species and used a statistical discriminant analysis to predict the likelihood of transmission among species. CONCLUSIONS: This study is an attempt to predict zoonosis through simple computational analysis of receptor sequence differences. Our method may be useful in predicting the zoonotic potential of newly discovered viral strains.",2011 Apr 13,"['Bae, Se-Eun', 'Son, Hyeon Seok']",BMC Bioinformatics,,,True
bd0d94a4452f2b55cfab53adecb84ce5f2c91fe3,PMC,Lysosomotropic agents as HCV entry inhibitors,http://dx.doi.org/10.1186/1743-422X-8-163,PMC3090357,21481279,CC BY,"HCV has two envelop proteins named as E1 and E2 which play an important role in cell entry through two main pathways: direct fusion at the plasma membrane and receptor-mediated endocytosis. Fusion of the HCV envelope proteins is triggered by low pH within the endosome. Lysosomotropic agents (LA) such as Chloroquine and Ammonium chloride (NH(4)Cl) are the weak bases and penetrate in lysosome as protonated form and increase the intracellular pH. To investigate the antiviral effect of LA (Chloroquine and NH(4)Cl) on pH dependent endocytosis, HCV pseudoparticles (HCVpp) of 1a and 3a genotype were produced and used to infect liver cells. The toxicological effects of Chloroquine and NH(4)Cl were tested in liver cells through MTT cell proliferation assay. For antiviral screening of Chloroquine and NH(4)Cl, liver cells were infected with HCVpp of 3a and 1a genotype in the presence or absence of different concentrations of Chloroquine and NH4Cl and there luciferase activity was determined by using a luminometer. The results demonstrated that Chloroquine and NH(4)Cl showed more than 50% reduction of virus infectivity at 50 μM and 10 mM concentrations respectively. These results suggest that inhibition of HCV at fusion step by increasing the lysosomal pH will be better option to treat chronic HCV.",2011 Apr 12,"['Ashfaq, Usman A', 'Javed, Tariq', 'Rehman, Sidra', 'Nawaz, Zafar', 'Riazuddin, Sheikh']",Virol J,,,True
f5fb2153b992cdc2d4bdb3678e667126c9a27689,PMC,One health: the importance of companion animal vector-borne diseases,http://dx.doi.org/10.1186/1756-3305-4-49,PMC3090364,21489237,CC BY,"The international prominence accorded the 'One Health' concept of co-ordinated activity of those involved in human and animal health is a modern incarnation of a long tradition of comparative medicine, with roots in the ancient civilizations and a golden era during the 19(th )century explosion of knowledge in the field of infectious disease research. Modern One Health tends to focus on zoonotic pathogens emerging from wildlife and production animal species, but one of the most significant One Health challenges is rabies for which there is a canine reservoir. This review considers the role of small companion animals in One Health and specifically addresses the major vector-borne infectious diseases that are shared by man, dogs and cats. The most significant of these are leishmaniosis, borreliosis, bartonellosis, ehrlichiosis, rickettsiosis and anaplasmosis. The challenges that lie ahead in this field of One Health are discussed, together with the role of the newly formed World Small Animal Veterinary Association One Health Committee.",2011 Apr 13,"Day, Michael J",Parasit Vectors,,,True
133933d03341e293921239f0d6a2b3ea4f1f574c,PMC,"A Simple, Inexpensive Device for Nucleic Acid Amplification without Electricity—Toward Instrument-Free Molecular Diagnostics in Low-Resource Settings",http://dx.doi.org/10.1371/journal.pone.0019738,PMC3090398,21573065,CC BY,"BACKGROUND: Molecular assays targeted to nucleic acid (NA) markers are becoming increasingly important to medical diagnostics. However, these are typically confined to wealthy, developed countries; or, to the national reference laboratories of developing-world countries. There are many infectious diseases that are endemic in low-resource settings (LRS) where the lack of simple, instrument-free, NA diagnostic tests is a critical barrier to timely treatment. One of the primary barriers to the practicality and availability of NA assays in LRS has been the complexity and power requirements of polymerase chain reaction (PCR) instrumentation (another is sample preparation). METHODOLOGY/PRINCIPAL FINDINGS: In this article, we investigate the hypothesis that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays. We assess the heater's equivalence to commercially available PCR instruments through the characterization of the temperature profiles produced, and a minimal method comparison. Versions of the prototype for several different isothermal techniques are presented. CONCLUSIONS/SIGNIFICANCE: We demonstrate that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays, and that the results of those assays are not significantly different from ones incubated in parallel in commercially available PCR instruments. These results clearly suggest the potential of the non-instrumented nucleic acid amplification (NINA) heater for molecular diagnostics in LRS. When combined with other innovations in development that eliminate power requirements for sample preparation, cold reagent storage, and readout, the NINA heater will comprise part of a kit that should enable electricity-free NA testing for many important analytes.",2011 May 9,"['LaBarre, Paul', 'Hawkins, Kenneth R.', 'Gerlach, Jay', 'Wilmoth, Jared', 'Beddoe, Andrew', 'Singleton, Jered', 'Boyle, David', 'Weigl, Bernhard']",PLoS One,,,True
c9e36f5f3564f04bfbbcefe1d1eec41078b2eadd,PMC,"A Simple, Inexpensive Device for Nucleic Acid Amplification without Electricity—Toward Instrument-Free Molecular Diagnostics in Low-Resource Settings",http://dx.doi.org/10.1371/journal.pone.0019738,PMC3090398,21573065,CC BY,"BACKGROUND: Molecular assays targeted to nucleic acid (NA) markers are becoming increasingly important to medical diagnostics. However, these are typically confined to wealthy, developed countries; or, to the national reference laboratories of developing-world countries. There are many infectious diseases that are endemic in low-resource settings (LRS) where the lack of simple, instrument-free, NA diagnostic tests is a critical barrier to timely treatment. One of the primary barriers to the practicality and availability of NA assays in LRS has been the complexity and power requirements of polymerase chain reaction (PCR) instrumentation (another is sample preparation). METHODOLOGY/PRINCIPAL FINDINGS: In this article, we investigate the hypothesis that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays. We assess the heater's equivalence to commercially available PCR instruments through the characterization of the temperature profiles produced, and a minimal method comparison. Versions of the prototype for several different isothermal techniques are presented. CONCLUSIONS/SIGNIFICANCE: We demonstrate that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays, and that the results of those assays are not significantly different from ones incubated in parallel in commercially available PCR instruments. These results clearly suggest the potential of the non-instrumented nucleic acid amplification (NINA) heater for molecular diagnostics in LRS. When combined with other innovations in development that eliminate power requirements for sample preparation, cold reagent storage, and readout, the NINA heater will comprise part of a kit that should enable electricity-free NA testing for many important analytes.",2011 May 9,"['LaBarre, Paul', 'Hawkins, Kenneth R.', 'Gerlach, Jay', 'Wilmoth, Jared', 'Beddoe, Andrew', 'Singleton, Jered', 'Boyle, David', 'Weigl, Bernhard']",PLoS One,,,False
f426954f62f73eccb16b672e9e93dfb6d48af618,PMC,The Potential Influence of Common Viral Infections Diagnosed during Hospitalization among Critically Ill Patients in the United States,http://dx.doi.org/10.1371/journal.pone.0018890,PMC3091021,21573031,CC BY,"Viruses are the most common source of infection among immunocompetent individuals, yet they are not considered a clinically meaningful risk factor among the critically ill. This work examines the association of viral infections diagnosed during the hospital stay or not documented as present on admission to the outcomes of ICU patients with no evidence of immunosuppression on admission. This is a population-based retrospective cohort study of University HealthSystem Consortium (UHC) academic centers in the U.S. from the years 2006 to 2009. The UHC is an alliance of over 90% of the non-profit academic medical centers in the U.S. A total of 209,695 critically ill patients were used in this analysis. Eight hospital complications were examined. Patients were grouped into four cohorts: absence of infection, bacterial infection only, viral infection only, and bacterial and viral infection during same hospital admission. Viral infections diagnosed during hospitalization significantly increased the risk of all complications. There was also a seasonal pattern for viral infections. Specific viruses associated with poor outcomes included influenza, RSV, CMV, and HSV. Patients who had both viral and bacterial infections during the same hospitalization had the greatest risk of mortality RR 6.58, 95% CI (5.47, 7.91); multi-organ failure RR 8.25, 95% CI (7.50, 9.07); and septic shock RR 271.2, 95% CI (188.0, 391.3). Viral infections may play a significant yet unrecognized role in the outcomes of ICU patients. They may serve as biological markers or play an active role in the development of certain adverse complications by interacting with coincident bacterial infection.",2011 Apr 29,"['Miggins, Makesha', 'Hasan, Anjum', 'Hohmann, Samuel', 'Southwick, Frederick', 'Casella, George', 'Schain, Denise', 'Liu, Huazhi', 'Bihorac, Azra', 'Moldawer, Lyle', 'Efron, Philip', 'Ang, Darwin']",PLoS One,,,True
04b9001d61d666e065f28a9e628991f4d76d71bc,PMC,"Perceived risk, anxiety, and behavioural responses of the general public during the early phase of the Influenza A (H1N1) pandemic in the Netherlands: results of three consecutive online surveys",http://dx.doi.org/10.1186/1471-2458-11-2,PMC3091536,21199571,CC BY,"BACKGROUND: Research into risk perception and behavioural responses in case of emerging infectious diseases is still relatively new. The aim of this study was to examine perceptions and behaviours of the general public during the early phase of the Influenza A (H1N1) pandemic in the Netherlands. METHODS: Two cross-sectional and one follow-up online survey (survey 1, 30 April-4 May; survey 2, 15-19 June; survey 3, 11-20 August 2009). Adults aged 18 years and above participating in a representative Internet panel were invited (survey 1, n = 456; survey 2, n = 478; follow-up survey 3, n = 934). Main outcome measures were 1) time trends in risk perception, feelings of anxiety, and behavioural responses (survey 1-3) and 2) factors associated with taking preventive measures and strong intention to comply with government-advised preventive measures in the future (survey 3). RESULTS: Between May and August 2009, the level of knowledge regarding Influenza A (H1N1) increased, while perceived severity of the new flu, perceived self-efficacy, and intention to comply with preventive measures decreased. The perceived reliability of information from the government decreased from May to August (62% versus 45%). Feelings of anxiety decreased from May to June, and remained stable afterwards. From June to August 2009, perceived vulnerability increased and more respondents took preventive measures (14% versus 38%). Taking preventive measures was associated with no children in the household, high anxiety, high self-efficacy, more agreement with statements on avoidance, and paying much attention to media information regarding Influenza A (H1N1). Having a strong intention to comply with government-advised preventive measures in the future was associated with higher age, high perceived severity, high anxiety, high perceived efficacy of measures, high self-efficacy, and finding governmental information to be reliable. CONCLUSIONS: Decreasing trends over time in perceived severity and anxiety are consistent with the reality: the clinical picture of influenza turned out to be mild in course of time. Although (inter)national health authorities initially overestimated the case fatality rate, the public stayed calm and remained to have a relatively high intention to comply with preventive measures.",2011 Jan 3,"['Bults, Marloes', 'Beaujean, Desirée JMA', 'de Zwart, Onno', 'Kok, Gerjo', 'van Empelen, Pepijn', 'van Steenbergen, Jim E', 'Richardus, Jan Hendrik', 'Voeten, Hélène ACM']",BMC Public Health,,,True
a8a55f01d9e4a3e3b77512767ab78bb8d1d74a25,PMC,Factors associated with motivation and hesitation to work among health professionals during a public crisis: a cross sectional study of hospital workers in Japan during the pandemic (H1N1) 2009,http://dx.doi.org/10.1186/1471-2458-10-672,PMC3091577,21050482,CC BY,"BACKGROUND: The professionalism of hospital workers in Japan was challenged by the pandemic (H1N1) 2009. To maintain hospital function under critical situations such as a pandemic, it is important to understand the factors that increase and decrease the willingness to work. Previous hospital-based studies have examined this question using hypothetical events, but so far it has not been examined in an actual pandemic. Here, we surveyed the factors that influenced the motivation and hesitation of hospital workers to work in Japan soon after the pandemic (H1N1) 2009. METHODS: Self-administered anonymous questionnaires about demographic character and stress factors were distributed to all 3635 employees at three core hospitals in Kobe city, Japan and were collected from June to July, 2009, about one month after the pandemic (H1N1) in Japan. RESULTS: Of a total of 3635 questionnaires distributed, 1693 (46.7%) valid questionnaires were received. 28.4% (N = 481) of workers had strong motivation and 14.7% (N = 249) had strong hesitation to work. Demographic characters and stress-related questions were categorised into four types according to the odds ratios (OR) of motivation and hesitation to work: some factors increased motivation and lowered hesitation; others increased motivation only; others increased hesitation only and others increased both motivation and hesitation. The strong feeling of being supported by the national and local governments (Multivariate OR: motivation; 3.5; CI 2.2-5.4, hesitation; 0.2; CI 0.1-0.6) and being protected by hospital (Multivariate OR: motivation; 2.8; CI 2.2-3.7, hesitation; 0.5; CI 0.3-0.7) were related to higher motivation and lower hesitation. Here, protection included taking precautions to prevent illness among workers and their families, providing for the care of those who do become ill, reducing malpractice threats, and financial support for families of workers who die on duty. But 94.1% of the respondents answered protection by the national and local government was weak and 79.7% answered protection by the hospital was weak. CONCLUSIONS: Some factors have conflicting effects because they increase both motivation and hesitation. Giving workers the feeling that they are being protected by the national and local government and hospital is especially valuable because it increases their motivation and lowers their hesitation to work.",2010 Nov 4,"['Imai, Hissei', 'Matsuishi, Kunitaka', 'Ito, Atsushi', 'Mouri, Kentaro', 'Kitamura, Noboru', 'Akimoto, Keiko', 'Mino, Koichi', 'Kawazoe, Ayako', 'Isobe, Masanori', 'Takamiya, Shizuo', 'Mita, Tatsuo']",BMC Public Health,,,True
924313134ea2e38b9e48ceaa1177afb92f7a5c03,PMC,Chiropteran types I and II interferon genes inferred from genome sequencing traces by a statistical gene-family assembler,http://dx.doi.org/10.1186/1471-2164-11-444,PMC3091641,20663124,CC BY,"BACKGROUND: The rate of emergence of human pathogens is steadily increasing; most of these novel agents originate in wildlife. Bats, remarkably, are the natural reservoirs of many of the most pathogenic viruses in humans. There are two bat genome projects currently underway, a circumstance that promises to speed the discovery host factors important in the coevolution of bats with their viruses. These genomes, however, are not yet assembled and one of them will provide only low coverage, making the inference of most genes of immunological interest error-prone. Many more wildlife genome projects are underway and intend to provide only shallow coverage. RESULTS: We have developed a statistical method for the assembly of gene families from partial genomes. The method takes full advantage of the quality scores generated by base-calling software, incorporating them into a complete probabilistic error model, to overcome the limitation inherent in the inference of gene family members from partial sequence information. We validated the method by inferring the human IFNA genes from the genome trace archives, and used it to infer 61 type-I interferon genes, and single type-II interferon genes in the bats Pteropus vampyrus and Myotis lucifugus. We confirmed our inferences by direct cloning and sequencing of IFNA, IFNB, IFND, and IFNK in P. vampyrus, and by demonstrating transcription of some of the inferred genes by known interferon-inducing stimuli. CONCLUSION: The statistical trace assembler described here provides a reliable method for extracting information from the many available and forthcoming partial or shallow genome sequencing projects, thereby facilitating the study of a wider variety of organisms with ecological and biomedical significance to humans than would otherwise be possible.",2010 Jul 21,"['Kepler, Thomas B', 'Sample, Christopher', 'Hudak, Kathryn', 'Roach, Jeffrey', 'Haines, Albert', 'Walsh, Allyson', 'Ramsburg, Elizabeth A']",BMC Genomics,,,True
f161447bea90a1e414e3cb22557efe9156bab8e2,PMC,Use of consensus sequences for the design of high density resequencing microarrays: the influenza virus paradigm,http://dx.doi.org/10.1186/1471-2164-11-586,PMC3091733,20961419,CC BY,"BACKGROUND: A resequencing microarray called PathogenID v2.0 has been developed and used to explore various strategies of sequence selection for its design. The part dedicated to influenza viruses was based on consensus sequences specific for one gene generated from global alignments of a large number of influenza virus sequences available in databanks. RESULTS: For each HA (H1, H2, H3, H5, H7 and H9) and NA (N1, N2 and N7) molecular type chosen to be tested, 1 to 3 consensus sequences were computed and tiled on the microarray. A total of 12 influenza virus samples from different host origins (humans, pigs, horses and birds) and isolated over a period of about 50 years were used in this study. Influenza viruses were correctly identified, and in most cases with the accurate information of the time of their emergence. CONCLUSIONS: PathogenID v2.0 microarray demonstrated its ability to type and subtype influenza viruses, often to the level of viral variants, with a minimum number of tiled sequences. This validated the strategy of using consensus sequences, which do not exist in nature, for our microarray design. The versatility, rapidity and high discriminatory power of the PathogenID v2.0 microarray could prove critical to detect and identify viral genome reassortment events resulting in a novel virus with epidemic or pandemic potential and therefore assist health authorities to make efficient decisions about patient treatment and outbreak management.",2010 Oct 20,"['Leclercq, India', 'Berthet, Nicolas', 'Batéjat, Christophe', 'Rousseaux, Claudine', 'Dickinson, Philip', 'Old, Iain G', 'Kong, Katherine', 'Kennedy, Giulia C', 'Cole, Stewart T', 'Manuguerra, Jean-Claude']",BMC Genomics,,,True
9580bfcbdb77b78a21887a8911bb9b69444182a4,PMC,Field Effectiveness of Pandemic and 2009-2010 Seasonal Vaccines against 2009-2010 A(H1N1) Influenza: Estimations from Surveillance Data in France,http://dx.doi.org/10.1371/journal.pone.0019621,PMC3091864,21573005,CC BY,"BACKGROUND: In this study, we assess how effective pandemic and trivalent 2009-2010 seasonal vaccines were in preventing influenza-like illness (ILI) during the 2009 A(H1N1) pandemic in France. We also compare vaccine effectiveness against ILI versus laboratory-confirmed pandemic A(H1N1) influenza, and assess the possible bias caused by using non-specific endpoints and observational data. METHODOLOGY AND PRINCIPAL FINDINGS: We estimated vaccine effectiveness by using the following formula: VE  =  (PPV-PCV)/(PPV(1-PCV)) × 100%, where PPV is the proportion vaccinated in the population and PCV the proportion of vaccinated influenza cases. People were considered vaccinated three weeks after receiving a dose of vaccine. ILI and pandemic A(H1N1) laboratory-confirmed cases were obtained from two surveillance networks of general practitioners. During the epidemic, 99.7% of influenza isolates were pandemic A(H1N1). Pandemic and seasonal vaccine uptakes in the population were obtained from the National Health Insurance database and by telephonic surveys, respectively. Effectiveness estimates were adjusted by age and week. The presence of residual biases was explored by calculating vaccine effectiveness after the influenza period. The effectiveness of pandemic vaccines in preventing ILI was 52% (95% confidence interval: 30–69) during the pandemic and 33% (4–55) after. It was 86% (56–98) against confirmed influenza. The effectiveness of seasonal vaccines against ILI was 61% (56–66) during the pandemic and 19% (−10–41) after. It was 60% (41–74) against confirmed influenza. CONCLUSIONS: The effectiveness of pandemic vaccines in preventing confirmed pandemic A(H1N1) influenza on the field was high, consistently with published findings. It was significantly lower against ILI. This is unsurprising since not all ILI cases are caused by influenza. Trivalent 2009-2010 seasonal vaccines had a statistically significant effectiveness in preventing ILI and confirmed pandemic influenza, but were not better in preventing confirmed pandemic influenza than in preventing ILI. This lack of difference might be indicative of selection bias.",2011 May 10,"['Pelat, Camille', 'Falchi, Alessandra', 'Carrat, Fabrice', 'Mosnier, Anne', 'Bonmarin, Isabelle', 'Turbelin, Clément', 'Vaux, Sophie', 'van der Werf, Sylvie', 'Cohen, Jean Marie', 'Lina, Bruno', 'Blanchon, Thierry', 'Hanslik, Thomas']",PLoS One,,,True
aad82670f39f4f9731dfeab9064d1063d13c5cb8,PMC,SAGES: A Suite of Freely-Available Software Tools for Electronic Disease Surveillance in Resource-Limited Settings,http://dx.doi.org/10.1371/journal.pone.0019750,PMC3091876,21572957,CC0,"Public health surveillance is undergoing a revolution driven by advances in the field of information technology. Many countries have experienced vast improvements in the collection, ingestion, analysis, visualization, and dissemination of public health data. Resource-limited countries have lagged behind due to challenges in information technology infrastructure, public health resources, and the costs of proprietary software. The Suite for Automated Global Electronic bioSurveillance (SAGES) is a collection of modular, flexible, freely-available software tools for electronic disease surveillance in resource-limited settings. One or more SAGES tools may be used in concert with existing surveillance applications or the SAGES tools may be used en masse for an end-to-end biosurveillance capability. This flexibility allows for the development of an inexpensive, customized, and sustainable disease surveillance system. The ability to rapidly assess anomalous disease activity may lead to more efficient use of limited resources and better compliance with World Health Organization International Health Regulations.",2011 May 10,"['Lewis, Sheri L.', 'Feighner, Brian H.', 'Loschen, Wayne A.', 'Wojcik, Richard A.', 'Skora, Joseph F.', 'Coberly, Jacqueline S.', 'Blazes, David L.']",PLoS One,,,True
a3ad970870495c1bc1fd7cc4eb6f815b486479c8,PMC,"The Global Emerging Infection Surveillance and Response System (GEIS), a U.S. government tool for improved global biosurveillance: a review of 2009",http://dx.doi.org/10.1186/1471-2458-11-S2-S2,PMC3092412,21388562,CC BY,"The Armed Forces Health Surveillance Center, Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) has the mission of performing surveillance for emerging infectious diseases that could affect the United States (U.S.) military. This mission is accomplished by orchestrating a global portfolio of surveillance projects, capacity-building efforts, outbreak investigations and training exercises. In 2009, this portfolio involved 39 funded partners, impacting 92 countries. This article discusses the current biosurveillance landscape, programmatic details of organization and implementation, and key contributions to force health protection and global public health in 2009.",2011 Mar 4,"['Russell, Kevin L', 'Rubenstein, Jennifer', 'Burke, Ronald L', 'Vest, Kelly G', 'Johns, Matthew C', 'Sanchez, Jose L', 'Meyer, William', 'Fukuda, Mark M', 'Blazes, David L']",BMC Public Health,,,True
6b18559c0c4de907cce17857d77321b52375ea36,PMC,Quantitative Subcellular Proteome and Secretome Profiling of Influenza A Virus-Infected Human Primary Macrophages,http://dx.doi.org/10.1371/journal.ppat.1001340,PMC3093355,21589892,CC BY,"Influenza A viruses are important pathogens that cause acute respiratory diseases and annual epidemics in humans. Macrophages recognize influenza A virus infection with their pattern recognition receptors, and are involved in the activation of proper innate immune response. Here, we have used high-throughput subcellular proteomics combined with bioinformatics to provide a global view of host cellular events that are activated in response to influenza A virus infection in human primary macrophages. We show that viral infection regulates the expression and/or subcellular localization of more than one thousand host proteins at early phases of infection. Our data reveals that there are dramatic changes in mitochondrial and nuclear proteomes in response to infection. We show that a rapid cytoplasmic leakage of lysosomal proteins, including cathepsins, followed by their secretion, contributes to inflammasome activation and apoptosis seen in the infected macrophages. Also, our results demonstrate that P2X(7) receptor and src tyrosine kinase activity are essential for inflammasome activation during influenza A virus infection. Finally, we show that influenza A virus infection is associated with robust secretion of different danger-associated molecular patterns (DAMPs) suggesting an important role for DAMPs in host response to influenza A virus infection. In conclusion, our high-throughput quantitative proteomics study provides important new insight into host-response against influenza A virus infection in human primary macrophages.",2011 May 12,"['Lietzén, Niina', 'Öhman, Tiina', 'Rintahaka, Johanna', 'Julkunen, Ilkka', 'Aittokallio, Tero', 'Matikainen, Sampsa', 'Nyman, Tuula A.']",PLoS Pathog,,,True
51f1e5b9a98b24f99b3d71b59b85c9bba957660c,PMC,Quantitative Subcellular Proteome and Secretome Profiling of Influenza A Virus-Infected Human Primary Macrophages,http://dx.doi.org/10.1371/journal.ppat.1001340,PMC3093355,21589892,CC BY,"Influenza A viruses are important pathogens that cause acute respiratory diseases and annual epidemics in humans. Macrophages recognize influenza A virus infection with their pattern recognition receptors, and are involved in the activation of proper innate immune response. Here, we have used high-throughput subcellular proteomics combined with bioinformatics to provide a global view of host cellular events that are activated in response to influenza A virus infection in human primary macrophages. We show that viral infection regulates the expression and/or subcellular localization of more than one thousand host proteins at early phases of infection. Our data reveals that there are dramatic changes in mitochondrial and nuclear proteomes in response to infection. We show that a rapid cytoplasmic leakage of lysosomal proteins, including cathepsins, followed by their secretion, contributes to inflammasome activation and apoptosis seen in the infected macrophages. Also, our results demonstrate that P2X(7) receptor and src tyrosine kinase activity are essential for inflammasome activation during influenza A virus infection. Finally, we show that influenza A virus infection is associated with robust secretion of different danger-associated molecular patterns (DAMPs) suggesting an important role for DAMPs in host response to influenza A virus infection. In conclusion, our high-throughput quantitative proteomics study provides important new insight into host-response against influenza A virus infection in human primary macrophages.",2011 May 12,"['Lietzén, Niina', 'Öhman, Tiina', 'Rintahaka, Johanna', 'Julkunen, Ilkka', 'Aittokallio, Tero', 'Matikainen, Sampsa', 'Nyman, Tuula A.']",PLoS Pathog,,,False
c5cbc7143785255c085b66a096790c84660dd1ec,PMC,Quantitative Subcellular Proteome and Secretome Profiling of Influenza A Virus-Infected Human Primary Macrophages,http://dx.doi.org/10.1371/journal.ppat.1001340,PMC3093355,21589892,CC BY,"Influenza A viruses are important pathogens that cause acute respiratory diseases and annual epidemics in humans. Macrophages recognize influenza A virus infection with their pattern recognition receptors, and are involved in the activation of proper innate immune response. Here, we have used high-throughput subcellular proteomics combined with bioinformatics to provide a global view of host cellular events that are activated in response to influenza A virus infection in human primary macrophages. We show that viral infection regulates the expression and/or subcellular localization of more than one thousand host proteins at early phases of infection. Our data reveals that there are dramatic changes in mitochondrial and nuclear proteomes in response to infection. We show that a rapid cytoplasmic leakage of lysosomal proteins, including cathepsins, followed by their secretion, contributes to inflammasome activation and apoptosis seen in the infected macrophages. Also, our results demonstrate that P2X(7) receptor and src tyrosine kinase activity are essential for inflammasome activation during influenza A virus infection. Finally, we show that influenza A virus infection is associated with robust secretion of different danger-associated molecular patterns (DAMPs) suggesting an important role for DAMPs in host response to influenza A virus infection. In conclusion, our high-throughput quantitative proteomics study provides important new insight into host-response against influenza A virus infection in human primary macrophages.",2011 May 12,"['Lietzén, Niina', 'Öhman, Tiina', 'Rintahaka, Johanna', 'Julkunen, Ilkka', 'Aittokallio, Tero', 'Matikainen, Sampsa', 'Nyman, Tuula A.']",PLoS Pathog,,,False
c6efc774a6d8d192e884408a84c8aa69ff385055,PMC,Quantitative Subcellular Proteome and Secretome Profiling of Influenza A Virus-Infected Human Primary Macrophages,http://dx.doi.org/10.1371/journal.ppat.1001340,PMC3093355,21589892,CC BY,"Influenza A viruses are important pathogens that cause acute respiratory diseases and annual epidemics in humans. Macrophages recognize influenza A virus infection with their pattern recognition receptors, and are involved in the activation of proper innate immune response. Here, we have used high-throughput subcellular proteomics combined with bioinformatics to provide a global view of host cellular events that are activated in response to influenza A virus infection in human primary macrophages. We show that viral infection regulates the expression and/or subcellular localization of more than one thousand host proteins at early phases of infection. Our data reveals that there are dramatic changes in mitochondrial and nuclear proteomes in response to infection. We show that a rapid cytoplasmic leakage of lysosomal proteins, including cathepsins, followed by their secretion, contributes to inflammasome activation and apoptosis seen in the infected macrophages. Also, our results demonstrate that P2X(7) receptor and src tyrosine kinase activity are essential for inflammasome activation during influenza A virus infection. Finally, we show that influenza A virus infection is associated with robust secretion of different danger-associated molecular patterns (DAMPs) suggesting an important role for DAMPs in host response to influenza A virus infection. In conclusion, our high-throughput quantitative proteomics study provides important new insight into host-response against influenza A virus infection in human primary macrophages.",2011 May 12,"['Lietzén, Niina', 'Öhman, Tiina', 'Rintahaka, Johanna', 'Julkunen, Ilkka', 'Aittokallio, Tero', 'Matikainen, Sampsa', 'Nyman, Tuula A.']",PLoS Pathog,,,False
f6daf6c68dd64802a28484b24191ff6e477d49b1,PMC,Quantitative Subcellular Proteome and Secretome Profiling of Influenza A Virus-Infected Human Primary Macrophages,http://dx.doi.org/10.1371/journal.ppat.1001340,PMC3093355,21589892,CC BY,"Influenza A viruses are important pathogens that cause acute respiratory diseases and annual epidemics in humans. Macrophages recognize influenza A virus infection with their pattern recognition receptors, and are involved in the activation of proper innate immune response. Here, we have used high-throughput subcellular proteomics combined with bioinformatics to provide a global view of host cellular events that are activated in response to influenza A virus infection in human primary macrophages. We show that viral infection regulates the expression and/or subcellular localization of more than one thousand host proteins at early phases of infection. Our data reveals that there are dramatic changes in mitochondrial and nuclear proteomes in response to infection. We show that a rapid cytoplasmic leakage of lysosomal proteins, including cathepsins, followed by their secretion, contributes to inflammasome activation and apoptosis seen in the infected macrophages. Also, our results demonstrate that P2X(7) receptor and src tyrosine kinase activity are essential for inflammasome activation during influenza A virus infection. Finally, we show that influenza A virus infection is associated with robust secretion of different danger-associated molecular patterns (DAMPs) suggesting an important role for DAMPs in host response to influenza A virus infection. In conclusion, our high-throughput quantitative proteomics study provides important new insight into host-response against influenza A virus infection in human primary macrophages.",2011 May 12,"['Lietzén, Niina', 'Öhman, Tiina', 'Rintahaka, Johanna', 'Julkunen, Ilkka', 'Aittokallio, Tero', 'Matikainen, Sampsa', 'Nyman, Tuula A.']",PLoS Pathog,,,False
50e8d64761dddc0b7ce037734d813eca7cd63701,PMC,"Alphacoronaviruses in New World Bats: Prevalence, Persistence, Phylogeny, and Potential for Interaction with Humans",http://dx.doi.org/10.1371/journal.pone.0019156,PMC3093381,21589915,CC0,"Bats are reservoirs for many different coronaviruses (CoVs) as well as many other important zoonotic viruses. We sampled feces and/or anal swabs of 1,044 insectivorous bats of 2 families and 17 species from 21 different locations within Colorado from 2007 to 2009. We detected alphacoronavirus RNA in bats of 4 species: big brown bats (Eptesicus fuscus), 10% prevalence; long-legged bats (Myotis volans), 8% prevalence; little brown bats (Myotis lucifugus), 3% prevalence; and western long-eared bats (Myotis evotis), 2% prevalence. Overall, juvenile bats were twice as likely to be positive for CoV RNA as adult bats. At two of the rural sampling sites, CoV RNAs were detected in big brown and long-legged bats during the three sequential summers of this study. CoV RNA was detected in big brown bats in all five of the urban maternity roosts sampled throughout each of the periods tested. Individually tagged big brown bats that were positive for CoV RNA and later sampled again all became CoV RNA negative. Nucleotide sequences in the RdRp gene fell into 3 main clusters, all distinct from those of Old World bats. Similar nucleotide sequences were found in amplicons from gene 1b and the spike gene in both a big-brown and a long-legged bat, indicating that a CoV may be capable of infecting bats of different genera. These data suggest that ongoing evolution of CoVs in bats creates the possibility of a continued threat for emergence into hosts of other species. Alphacoronavirus RNA was detected at a high prevalence in big brown bats in roosts in close proximity to human habitations (10%) and known to have direct contact with people (19%), suggesting that significant potential opportunities exist for cross-species transmission of these viruses. Further CoV surveillance studies in bats throughout the Americas are warranted.",2011 May 12,"['Osborne, Christina', 'Cryan, Paul M.', ""O'Shea, Thomas J."", 'Oko, Lauren M.', 'Ndaluka, Christina', 'Calisher, Charles H.', 'Berglund, Andrew D.', 'Klavetter, Mead L.', 'Bowen, Richard A.', 'Holmes, Kathryn V.', 'Dominguez, Samuel R.']",PLoS One,,,True
2e7571bccf8e71340eae54a7254aa136d0cbbcb3,PMC,Modeling the variations in pediatric respiratory syncytial virus seasonal epidemics,http://dx.doi.org/10.1186/1471-2334-11-105,PMC3094225,21510889,CC BY,"BACKGROUND: Seasonal respiratory syncytial virus (RSV) epidemics occur annually in temperate climates and result in significant pediatric morbidity and increased health care costs. Although RSV epidemics generally occur between October and April, the size and timing vary across epidemic seasons and are difficult to predict accurately. Prediction of epidemic characteristics would support management of resources and treatment. METHODS: The goals of this research were to examine the empirical relationships among early exponential growth rate, total epidemic size, and timing, and the utility of specific parameters in compartmental models of transmission in accounting for variation among seasonal RSV epidemic curves. RSV testing data from Primary Children's Medical Center were collected on children under two years of age (July 2001-June 2008). Simple linear regression was used explore the relationship between three epidemic characteristics (final epidemic size, days to peak, and epidemic length) and exponential growth calculated from four weeks of daily case data. A compartmental model of transmission was fit to the data and parameter estimated used to help describe the variation among seasonal RSV epidemic curves. RESULTS: The regression results indicated that exponential growth was correlated to epidemic characteristics. The transmission modeling results indicated that start time for the epidemic and the transmission parameter co-varied with the epidemic season. CONCLUSIONS: The conclusions were that exponential growth was somewhat empirically related to seasonal epidemic characteristics and that variation in epidemic start date as well as the transmission parameter over epidemic years could explain variation in seasonal epidemic size. These relationships are useful for public health, health care providers, and infectious disease researchers.",2011 Apr 21,"['Leecaster, Molly', 'Gesteland, Per', 'Greene, Tom', 'Walton, Nephi', 'Gundlapalli, Adi', 'Rolfs, Robert', 'Byington, Carrie', 'Samore, Matthew']",BMC Infect Dis,,,True
b34cc3d570e41a80c01088f73600357cf071a4da,PMC,Randomized placebo-controlled trial on azithromycin to reduce the morbidity of bronchiolitis in Indigenous Australian infants: rationale and protocol,http://dx.doi.org/10.1186/1745-6215-12-94,PMC3094234,21492416,CC BY,"BACKGROUND: Acute lower respiratory infections are the commonest cause of morbidity and potentially preventable mortality in Indigenous infants. Infancy is also a critical time for post-natal lung growth and development. Severe or repeated lower airway injury in very young children likely increases the likelihood of chronic pulmonary disorders later in life. Globally, bronchiolitis is the most common form of acute lower respiratory infections during infancy. Compared with non-Indigenous Australian infants, Indigenous infants have greater bacterial density in their upper airways and more severe bronchiolitis episodes. Our study tests the hypothesis that the anti-microbial and anti-inflammatory properties of azithromycin, improve the clinical outcomes of Indigenous Australian infants hospitalised with bronchiolitis. METHODS: We are conducting a dual centre, randomised, double-blind, placebo-controlled, parallel group trial in northern Australia. Indigenous infants (aged ≤ 24-months, expected number = 200) admitted to one of two regional hospitals (Darwin, Northern Territory and Townsville, Queensland) with a clinical diagnosis of bronchiolitis and fulfilling inclusion criteria are randomised (allocation concealed) to either azithromycin (30 mg/kg/dose) or placebo administered once weekly for three doses. Clinical data are recorded twice daily and nasopharyngeal swab are collected at enrolment and at the time of discharge from hospital. Primary outcomes are 'length of oxygen requirement' and 'duration of stay,' the latter based upon being judged as 'ready for respiratory discharge'. The main secondary outcome is readmission for a respiratory illness within 6-months of leaving hospital. Descriptive virological and bacteriological (including development of antibiotic resistance) data from nasopharyngeal samples will also be reported. DISCUSSION: Two published studies, both involving different patient populations and settings, as well as different macrolide antibiotics and treatment duration, have produced conflicting results. Our randomised, placebo-controlled trial of azithromycin in Indigenous infants hospitalised with bronchiolitis is designed to determine whether it can reduce short-term (and potentially long-term) morbidity from respiratory illness in Australian Indigenous infants who are at high risk of developing chronic respiratory illness. If azithromycin is efficacious in reducing the morbidly of Indigenous infants hospitalised with bronchiolitis, the intervention would lead to improved short term (and possibly long term) health benefits. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000326099",2011 Apr 14,"['Chang, Anne B', 'Grimwood, Keith', 'White, Andrew V', 'Maclennan, Carolyn', 'Sloots, Theo P', 'Sive, Alan', 'McCallum, Gabrielle B', 'Mackay, Ian M', 'Morris, Peter S']",Trials,,,True
a748ccbe075d2bc2223dae088c6014428992718d,PMC,Phylogenetic distribution and predominant genotype of the avian infectious bronchitis virus in China during 2008-2009,http://dx.doi.org/10.1186/1743-422X-8-184,PMC3094301,21510909,CC BY,"BACKGROUND: The nephropathogenic avian infectious bronchitis (IB) caused unprecedented economic losses to the commercial chicken industry of China in 2008-2009. To investigate the prevalence of nephropathogenic IB in China, eighty IBV isolates from different provinces during 2008-2009 were identified by dwarf embryo test and RT-PCR. RESULTS: The strains were mostly isolated in winter and spring with a wide age range of IB outbreaks, from 4 to 69 days. By the virus recovery trials, 70/80 of the strains resulted in the deaths or distresses of birds from nephritis. To learn more about the molecular evolutionary characteristics of the circulating field strains, the coding region of major spike 1 (S1) protein gene of these strains was RT-PCR amplified and sequenced. Compared to the published representative strains, nucleotides and amino acids sequence analysis indicated that the S1 genes of these strains and the reference strains displayed homologies ranging from 75.1% to 99.8% and from 73.1% to 99.8% respectively. S1 protein of the major pandemic strains contained 540 or 542 amino acids with the cleavage site of HRRRR or RRFRR. Phylogenetic analysis revealed that recent field isolates of IBV in China were mostly belonged to A2-branch (QXIBV-branch) and HN08-branch, only one isolate was belonged to Gray-branch and M41-branch respectively. Most of the 80 strains showed evolutionarily distant from vaccine strains. CONCLUSIONS: The results of this study suggested that nephropathogenic IBVs were mainly A2-like strains in China during 2008-2009.",2011 Apr 22,"['Ji, Jun', 'Xie, Jingwei', 'Chen, Feng', 'Shu, Dingming', 'Zuo, Kejing', 'Xue, Chunyi', 'Qin, Jianping', 'Li, Hongmei', 'Bi, Yingzuo', 'Ma, Jingyun', 'Xie, Qingmei']",Virol J,,,True
abf6f66d8e18b652d10944bb21e19debca5dc5e8,PMC,Analyzing Cytotoxic and Apoptogenic Properties of Scutellaria litwinowii Root Extract on Cancer Cell Lines,http://dx.doi.org/10.1093/ecam/nep214,PMC3094709,20028719,CC BY,"The Scutellaria species (Lamiaceae) is used as a source of flavonoids to treat a variety of diseases in traditional medicine. In spite of many reports about the cytotoxic and antitumor effects of some species of this genus, anticancer researches on one of the Iranian species S. litwinowii have not yet been conducted. The cytotoxic properties of total methanol extract of S. litwinowii and its fractions were investigated on different cancer cell lines including AGS, HeLa, MCF-7, PC12 and NIH 3T3. Meanwhile, the role of apoptosis in this toxicity was explored. The cells were cultured in DMEM medium and incubated with different concentrations of herb plant extracts. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using propidium iodide staining of DNA fragmentation by flow cytometry (sub-G1 peak). Scutellaria litwinowii inhibited the growth of malignant cells in a dose-dependent manner. Among solvent fractions of S. litwinowii, the methylene chloride fraction was found to be more toxic compared to other fractions. The IC(50) values of this fraction against AGS, HeLa, MCF-7 and PC12 cell lines after 24 h were determined, 121.2 ± 3.1, 40.9 ± 2.5, 115.9 ± 3.5 and 64.5 ± 3.4 μg/ml, respectively. Scutellaria litwinowii induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that apoptotic cell death is involved in S. litwinowii toxicity. Scutellaria litwinowii exerts cytotoxic and proapototic effects in a variety of malignant cell lines and could be considered as a potential chemotherapeutic agent in cancer treatment.",2011 Mar 9,"['Tayarani-Najaran, Zahra', 'Emami, Seyed Ahmad', 'Asili, Javad', 'Mirzaei, Alireza', 'Mousavi, Seyed Hadi']",Evid Based Complement Alternat Med,,,True
61d48e2dee3bd05595403b3e5115d88d4e1dad5d,PMC,Potent Host-Directed Small-Molecule Inhibitors of Myxovirus RNA-Dependent RNA-Polymerases,http://dx.doi.org/10.1371/journal.pone.0020069,PMC3095640,21603574,CC BY,"Therapeutic targeting of host cell factors required for virus replication rather than of pathogen components opens new perspectives to counteract virus infections. Anticipated advantages of this approach include a heightened barrier against the development of viral resistance and a broadened pathogen target spectrum. Myxoviruses are predominantly associated with acute disease and thus are particularly attractive for this approach since treatment time can be kept limited. To identify inhibitor candidates, we have analyzed hit compounds that emerged from a large-scale high-throughput screen for their ability to block replication of members of both the orthomyxovirus and paramyxovirus families. This has returned a compound class with broad anti-viral activity including potent inhibition of different influenza virus and paramyxovirus strains. After hit-to-lead chemistry, inhibitory concentrations are in the nanomolar range in the context of immortalized cell lines and human PBMCs. The compound shows high metabolic stability when exposed to human S-9 hepatocyte subcellular fractions. Antiviral activity is host-cell species specific and most pronounced in cells of higher mammalian origin, supporting a host-cell target. While the compound induces a temporary cell cycle arrest, host mRNA and protein biosynthesis are largely unaffected and treated cells maintain full metabolic activity. Viral replication is blocked at a post-entry step and resembles the inhibition profile of a known inhibitor of viral RNA-dependent RNA-polymerase (RdRp) activity. Direct assessment of RdRp activity in the presence of the reagent reveals strong inhibition both in the context of viral infection and in reporter-based minireplicon assays. In toto, we have identified a compound class with broad viral target range that blocks host factors required for viral RdRp activity. Viral adaptation attempts did not induce resistance after prolonged exposure, in contrast to rapid adaptation to a pathogen-directed inhibitor of RdRp activity.",2011 May 16,"['Krumm, Stefanie A.', 'Ndungu, J. Maina', 'Yoon, Jeong-Joong', 'Dochow, Melanie', 'Sun, Aiming', 'Natchus, Michael', 'Snyder, James P.', 'Plemper, Richard K.']",PLoS One,,,True
cc8dfecfa5e0494957bbb094ce7989400d549027,PMC,Potent Host-Directed Small-Molecule Inhibitors of Myxovirus RNA-Dependent RNA-Polymerases,http://dx.doi.org/10.1371/journal.pone.0020069,PMC3095640,21603574,CC BY,"Therapeutic targeting of host cell factors required for virus replication rather than of pathogen components opens new perspectives to counteract virus infections. Anticipated advantages of this approach include a heightened barrier against the development of viral resistance and a broadened pathogen target spectrum. Myxoviruses are predominantly associated with acute disease and thus are particularly attractive for this approach since treatment time can be kept limited. To identify inhibitor candidates, we have analyzed hit compounds that emerged from a large-scale high-throughput screen for their ability to block replication of members of both the orthomyxovirus and paramyxovirus families. This has returned a compound class with broad anti-viral activity including potent inhibition of different influenza virus and paramyxovirus strains. After hit-to-lead chemistry, inhibitory concentrations are in the nanomolar range in the context of immortalized cell lines and human PBMCs. The compound shows high metabolic stability when exposed to human S-9 hepatocyte subcellular fractions. Antiviral activity is host-cell species specific and most pronounced in cells of higher mammalian origin, supporting a host-cell target. While the compound induces a temporary cell cycle arrest, host mRNA and protein biosynthesis are largely unaffected and treated cells maintain full metabolic activity. Viral replication is blocked at a post-entry step and resembles the inhibition profile of a known inhibitor of viral RNA-dependent RNA-polymerase (RdRp) activity. Direct assessment of RdRp activity in the presence of the reagent reveals strong inhibition both in the context of viral infection and in reporter-based minireplicon assays. In toto, we have identified a compound class with broad viral target range that blocks host factors required for viral RdRp activity. Viral adaptation attempts did not induce resistance after prolonged exposure, in contrast to rapid adaptation to a pathogen-directed inhibitor of RdRp activity.",2011 May 16,"['Krumm, Stefanie A.', 'Ndungu, J. Maina', 'Yoon, Jeong-Joong', 'Dochow, Melanie', 'Sun, Aiming', 'Natchus, Michael', 'Snyder, James P.', 'Plemper, Richard K.']",PLoS One,,,True
015729be3f439e9ef2033276a4ef14df8873dda9,PMC,Screening for Antiviral Activities of Isolated Compounds from Essential Oils,http://dx.doi.org/10.1093/ecam/nep187,PMC3096453,20008902,CC BY,"Essential oil of star anise as well as phenylpropanoids and sesquiterpenes, for example, trans-anethole, eugenol, β-eudesmol, farnesol, β-caryophyllene and β-caryophyllene oxide, which are present in many essential oils, were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro. Antiviral activity was analyzed by plaque reduction assays and mode of antiviral action was determined by addition of the drugs to uninfected cells, to the virus prior to infection or to herpesvirus-infected cells. Star anise oil reduced viral infectivity by >99%, phenylpropanoids inhibited HSV infectivity by about 60–80% and sesquiterpenes suppressed herpes virus infection by 40–98%. Both, star anise essential oil and all isolated compounds exhibited anti-HSV-1 activity by direct inactivation of free virus particles in viral suspension assays. All tested drugs interacted in a dose-dependent manner with herpesvirus particles, thereby inactivating viral infectivity. Star anise oil, rich in trans-anethole, revealed a high selectivity index of 160 against HSV, whereas among the isolated compounds only β-caryophyllene displayed a high selectivity index of 140. The presence of β-caryophyllene in many essential oils might contribute strongly to their antiviral ability. These results indicate that phenylpropanoids and sesquiterpenes present in essential oils contribute to their antiviral activity against HSV.",2011 Feb 14,"['Astani, Akram', 'Reichling, Jürgen', 'Schnitzler, Paul']",Evid Based Complement Alternat Med,,,True
a4e72fc5914fe0e8387e5acce1aa3106705f7677,PMC,"Fever screening during the influenza (H1N1-2009) pandemic at Narita International Airport, Japan",http://dx.doi.org/10.1186/1471-2334-11-111,PMC3096599,21539735,CC BY,"BACKGROUND: Entry screening tends to start with a search for febrile international passengers, and infrared thermoscanners have been employed for fever screening in Japan. We aimed to retrospectively assess the feasibility of detecting influenza cases based on fever screening as a sole measure. METHODS: Two datasets were collected at Narita International Airport during the 2009 pandemic. The first contained confirmed influenza cases (n = 16) whose diagnosis took place at the airport during the early stages of the pandemic, and the second contained a selected and suspected fraction of passengers (self-reported or detected by an infrared thermoscanner; n = 1,049) screened from September 2009 to January 2010. The sensitivity of fever (38.0°C) for detecting H1N1-2009 was estimated, and the diagnostic performances of the infrared thermoscanners in detecting hyperthermia at cut-off levels of 37.5°C, 38.0°C and 38.5°C were also estimated. RESULTS: The sensitivity of fever for detecting H1N1-2009 cases upon arrival was estimated to be 22.2% (95% confidence interval: 0, 55.6) among nine confirmed H1N1-2009 cases, and 55.6% of the H1N1-2009 cases were under antipyretic medications upon arrival. The sensitivity and specificity of the infrared thermoscanners in detecting hyperthermia ranged from 50.8-70.4% and 63.6-81.7%, respectively. The positive predictive value appeared to be as low as 37.3-68.0%. CONCLUSIONS: The sensitivity of entry screening is a product of the sensitivity of fever for detecting influenza cases and the sensitivity of the infrared thermoscanners in detecting fever. Given the additional presence of confounding factors and unrestricted medications among passengers, reliance on fever alone is unlikely to be feasible as an entry screening measure.",2011 May 3,"['Nishiura, Hiroshi', 'Kamiya, Kazuko']",BMC Infect Dis,,,True
f3b7f4469ac01f1ce916d24172570c43c537627e,PMC,Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression,http://dx.doi.org/10.1371/journal.pone.0019705,PMC3096629,21611183,CC BY,"Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 µg/ml) but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 µg/ml or higher). Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.",2011 May 17,"['Michaelis, Martin', 'Geiler, Janina', 'Naczk, Patrizia', 'Sithisarn, Patchima', 'Leutz, Anke', 'Doerr, Hans Wilhelm', 'Cinatl, Jindrich']",PLoS One,,,True
3aa13ec4d39637c70526a5965f8e9cdad76855f0,PMC,Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression,http://dx.doi.org/10.1371/journal.pone.0019705,PMC3096629,21611183,CC BY,"Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 µg/ml) but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 µg/ml or higher). Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.",2011 May 17,"['Michaelis, Martin', 'Geiler, Janina', 'Naczk, Patrizia', 'Sithisarn, Patchima', 'Leutz, Anke', 'Doerr, Hans Wilhelm', 'Cinatl, Jindrich']",PLoS One,,,False
84be1a1130780982a380920c33e91c2d4b652d90,PMC,Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression,http://dx.doi.org/10.1371/journal.pone.0019705,PMC3096629,21611183,CC BY,"Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 µg/ml) but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 µg/ml or higher). Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.",2011 May 17,"['Michaelis, Martin', 'Geiler, Janina', 'Naczk, Patrizia', 'Sithisarn, Patchima', 'Leutz, Anke', 'Doerr, Hans Wilhelm', 'Cinatl, Jindrich']",PLoS One,,,False
074e144c6cc7fb9de0cc550d3e777a0ccfa97007,PMC,Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression,http://dx.doi.org/10.1371/journal.pone.0019705,PMC3096629,21611183,CC BY,"Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 µg/ml) but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 µg/ml or higher). Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.",2011 May 17,"['Michaelis, Martin', 'Geiler, Janina', 'Naczk, Patrizia', 'Sithisarn, Patchima', 'Leutz, Anke', 'Doerr, Hans Wilhelm', 'Cinatl, Jindrich']",PLoS One,,,False
68081e6d2768743855003f159baf5cb7ab59087d,PMC,A 5'-proximal Stem-loop Structure of 5' Untranslated Region of Porcine Reproductive and Respiratory Syndrome Virus Genome Is Key for Virus Replication,http://dx.doi.org/10.1186/1743-422X-8-172,PMC3096946,21496223,CC BY,"BACKGROUND: It has been well documented that the 5' untranslated region (5' UTR) of many positive-stranded RNA viruses contain key cis-acting regulatory sequences, as well as high-order structural elements. Little is known for such regulatory elements controlling porcine arterivirus replication. We investigated the roles of a conserved stem-loop 2 (SL2) that resides in the 5'UTR of the genome of a type II porcine reproductive and respiratory syndrome virus (PRRSV). RESULTS: We provided genetic evidences demonstrating that 1) the SL2 in type II PRRSV 5' UTR, N-SL2, could be structurally and functionally substituted by its counterpart in type I PRRSV, E-SL2; 2) the functionality of N-SL2 was dependent upon the G-C rich stem structure, while the ternary-loop size was irrelevant to RNA synthesis; 3) serial deletions showed that the stem integrity of N-SL2 was crucial for subgenomic mRNA synthesis; and 4) when extensive base-pairs in the stem region was deleted, an alternative N-SL2-like structure with different sequence was utilized for virus replication. CONCLUSION: Taken together, we concluded that the phylogenetically conserved SL2 in the 5' UTR was crucial for PRRSV virus replication, subgenomic mRNA synthesis in particular.",2011 Apr 15,"['Lu, Jiaqi', 'Gao, Fei', 'Wei, Zuzhang', 'Liu, Ping', 'Liu, Changlong', 'Zheng, Haihong', 'Li, Yanhua', 'Lin, Tao', 'Yuan, Shishan']",Virol J,,,True
4c59d82d87d20a5a5ab05c5c19895bda141167d4,PMC,Sometimes Sperm Whales (Physeter macrocephalus) Cannot Find Their Way Back to the High Seas: A Multidisciplinary Study on a Mass Stranding,http://dx.doi.org/10.1371/journal.pone.0019417,PMC3097202,21673789,CC BY,"BACKGROUND: Mass strandings of sperm whales (Physeter macrocephalus) remain peculiar and rather unexplained events, which rarely occur in the Mediterranean Sea. Solar cycles and related changes in the geomagnetic field, variations in water temperature and weather conditions, coast geographical features and human activities have been proposed as possible causes. In December 2009, a pod of seven male sperm whales stranded along the Adriatic coast of Southern Italy. This is the sixth instance from 1555 in this basin. METHODOLOGY/PRINCIPAL FINDINGS: Complete necropsies were performed on three whales whose bodies were in good condition, carrying out on sampled tissues histopathology, virology, bacteriology, parasitology, and screening of veins looking for gas emboli. Furthermore, samples for age determination, genetic studies, gastric content evaluation, stable isotopes and toxicology were taken from all the seven specimens. The animals were part of the same group and determined by genetic and photo-identification to be part of the Mediterranean population. Causes of death did not include biological agents, or the “gas and fat embolic syndrome”, associated with direct sonar exposure. Environmental pollutant tissue concentrations were relatively high, in particular organochlorinated xenobiotics. Gastric content and morphologic tissue examinations showed a prolonged starvation, which likely caused, at its turn, the mobilization of lipophilic contaminants from the adipose tissue. Chemical compounds subsequently entered the blood circulation and may have impaired immune and nervous functions. CONCLUSIONS/SIGNIFICANCE: A multi-factorial cause underlying this sperm whales' mass stranding is proposed herein based upon the results of postmortem investigations as well as of the detailed analyses of the geographical and historical background. The seven sperm whales took the same “wrong way” into the Adriatic Sea, a potentially dangerous trap for Mediterranean sperm whales. Seismic surveys should be also regarded as potential co-factors, even if no evidence of direct impact has been detected.",2011 May 18,"['Mazzariol, Sandro', 'Di Guardo, Giovanni', 'Petrella, Antonio', 'Marsili, Letizia', 'Fossi, Cristina M.', 'Leonzio, Claudio', 'Zizzo, Nicola', 'Vizzini, Salvatrice', 'Gaspari, Stefania', 'Pavan, Gianni', 'Podestà, Michela', 'Garibaldi, Fulvio', 'Ferrante, Margherita', 'Copat, Chiara', 'Traversa, Donato', 'Marcer, Federica', 'Airoldi, Sabina', 'Frantzis, Alexandros', 'De Bernaldo Quirós, Yara', 'Cozzi, Bruno', 'Fernández, Antonio']",PLoS One,,,True
39b557ab42e265c37acee079b474c73708f197c7,PMC,Insight into the Interaction of Metal Ions with TroA from Streptococcus suis,http://dx.doi.org/10.1371/journal.pone.0019510,PMC3097204,21611125,CC BY,"BACKGROUND: The scavenging ability of sufficient divalent metal ions is pivotal for pathogenic bacteria to survive in the host. ATP-binding cassette (ABC)-type metal transporters provide a considerable amount of different transition metals for bacterial growth. TroA is a substrate binding protein for uptake of multiple metal ions. However, the function and structure of the TroA homologue from the epidemic Streptococcus suis isolates (SsTroA) have not been characterized. METHODOLOGY/PRINCIPAL FINDINGS: Here we determined the crystal structure of SsTroA from a highly pathogenic streptococcal toxic shock syndrome (STSS)-causing Streptococcus suis in complex with zinc. Inductively coupled plasma mass spectrometry (ICP-MS) analysis revealed that apo-SsTroA binds Zn(2+) and Mn(2+). Both metals bind to SsTroA with nanomolar affinity and stabilize the protein against thermal unfolding. Zn(2+) and Mn(2+) induce distinct conformational changes in SsTroA compared with the apo form as confirmed by both circular dichroism (CD) and nuclear magnetic resonance (NMR) spectra. NMR data also revealed that Zn(2+)/Mn(2+) bind to SsTroA in either the same site or an adjacent region. Finally, we found that the folding of the metal-bound protein is more compact than the corresponding apoprotein. CONCLUSIONS/SIGNIFICANCE: Our findings reveal a mechanism for uptake of metal ions in S. suis and this mechanism provides a reasonable explanation as to how SsTroA operates in metal transport.",2011 May 18,"['Zheng, Beiwen', 'Zhang, Qiangmin', 'Gao, Jia', 'Han, Huiming', 'Li, Ming', 'Zhang, Jingren', 'Qi, Jianxun', 'Yan, Jinghua', 'Gao, George F.']",PLoS One,,,True
aa69482e261bf1d6546491ba52991ea1ac3402a1,PMC,"Identification of Mycobacterium tuberculosis-Specific Th1, Th17 and Th22 Cells Using the Expression of CD40L in Tuberculous Pleurisy",http://dx.doi.org/10.1371/journal.pone.0020165,PMC3097245,21625607,CC BY,"Important advances have been made in the immunodiagnosis of tuberculosis (TB) based on the detection of Mycobacterium tuberculosis (MTB)-specific T cells. However, the sensitivity and specificity of the immunological approach are relatively low because there are no specific markers for antigen-specific Th cells, and some of the Th cells that do not produce cytokines can be overlooked using this approach. In this study, we found that MTB-specific peptides of ESAT-6/CFP-10 can stimulate the expression of CD40L specifically in CD4(+) T cells but not other cells from pleural fluid cells (PFCs) in patients with tuberculous pleurisy (TBP). CD4(+)CD40L(+) but not CD4(+)CD40L(−) T cells express IFN-γ, IL-2, TNF-α, IL-17 or IL-22 after stimulation with MTB-specific peptides. In addition, CD4(+)CD40L(+) T cells were found to be mostly polyfunctional T cells that simultaneously produce IFN-γ, IL-2 and TNF-α and display an effector or effector memory phenotype (CD45RA(−)CD45RO(+)CCR7(−)CD62L(−)ICOS(−)). To determine the specificity of CD4(+)CD40L(+) T cells, we incubated PFCs with ESTA-6/CFP-10 peptides and sorted live CD4(+)CD40L(+) and CD4(+)CD40L(−) T cells by flow cytometry. We further demonstrated that sorted CD4(+)CD40L(+), but not CD4(+)CD40L(−) fractions, principally produced IFN-γ, IL-2, TNF-α, IL-17 and IL-22 following restimulation with ESTA-6/CFP-10 peptides. Taken together, our data indicate that the expression of CD40L on MTB-specific CD4(+) T cells could be a good marker for the evaluation and isolation of MTB-specific Th cells and might also be useful in the diagnosis of TB.",2011 May 18,"['Li, Li', 'Qiao, Dan', 'Fu, Xiaoying', 'Lao, Suihua', 'Zhang, Xianlan', 'Wu, Changyou']",PLoS One,,,True
9dc767a57df46887166f86194ad8fd2d94b6dba5,PMC,Chest imaging features of patients afflicted with Influenza A (H1N1) in a Malaysian tertiary referral centre,http://dx.doi.org/10.2349/biij.6.4.e35,PMC3097804,21611071,CC BY,"This is a retrospective descriptive study of the chest imaging findings of 118 patients with confirmed A(H1N1) in a tertiary referral centre. About 42% of the patients had positive initial chest radiographic (CXR) findings. The common findings were bi-basal air-space opacities and perihilar reticular and alveolar infiltrates. In select cases, high-resolution computed tomography (CT) imaging showed ground-glass change with some widespread reticular changes and atelectasis.",2010 Oct 1,"['Bux, SI', 'Mohd. Ramli, N', 'Ahmad Sarji, S', 'Kamarulzaman, A']",Biomed Imaging Interv J,,,True
e086d4275f9420065465a39f78c29bd36a5796d3,PMC,Using simple artificial intelligence methods for predicting amyloidogenesis in antibodies,http://dx.doi.org/10.1186/1471-2105-11-79,PMC3098112,20144194,CC BY,"BACKGROUND: All polypeptide backbones have the potential to form amyloid fibrils, which are associated with a number of degenerative disorders. However, the likelihood that amyloidosis would actually occur under physiological conditions depends largely on the amino acid composition of a protein. We explore using a naive Bayesian classifier and a weighted decision tree for predicting the amyloidogenicity of immunoglobulin sequences. RESULTS: The average accuracy based on leave-one-out (LOO) cross validation of a Bayesian classifier generated from 143 amyloidogenic sequences is 60.84%. This is consistent with the average accuracy of 61.15% for a holdout test set comprised of 103 AM and 28 non-amyloidogenic sequences. The LOO cross validation accuracy increases to 81.08% when the training set is augmented by the holdout test set. In comparison, the average classification accuracy for the holdout test set obtained using a decision tree is 78.64%. Non-amyloidogenic sequences are predicted with average LOO cross validation accuracies between 74.05% and 77.24% using the Bayesian classifier, depending on the training set size. The accuracy for the holdout test set was 89%. For the decision tree, the non-amyloidogenic prediction accuracy is 75.00%. CONCLUSIONS: This exploratory study indicates that both classification methods may be promising in providing straightforward predictions on the amyloidogenicity of a sequence. Nevertheless, the number of available sequences that satisfy the premises of this study are limited, and are consequently smaller than the ideal training set size. Increasing the size of the training set clearly increases the accuracy, and the expansion of the training set to include not only more derivatives, but more alignments, would make the method more sound. The accuracy of the classifiers may also be improved when additional factors, such as structural and physico-chemical data, are considered. The development of this type of classifier has significant applications in evaluating engineered antibodies, and may be adapted for evaluating engineered proteins in general.",2010 Feb 8,"['David, Maria Pamela C', 'Concepcion, Gisela P', 'Padlan, Eduardo A']",BMC Bioinformatics,,,True
3240298a10e4834230eabe0b7cb5a728c00779af,PMC,Murine immune responses to a Plasmodium vivax-derived chimeric recombinant protein expressed in Brassica napus,http://dx.doi.org/10.1186/1475-2875-10-106,PMC3098821,21529346,CC BY,"BACKGROUND: To develop a plant-based vaccine against Plasmodium vivax, two P. vivax candidate proteins were chosen. First, the merozoite surface protein-1 (MSP-1), a major asexual blood stage antigen that is currently considered a strong vaccine candidate. Second, the circumsporozoite protein (CSP), a component of sporozoites that contains a B-cell epitope. METHODS: A synthetic chimeric recombinant 516 bp gene encoding containing PvMSP-1, a Pro-Gly linker motif, and PvCSP was synthesized; the gene, named MLC, encoded a total of 172 amino acids. The recombinant gene was modified with regard to codon usage to optimize gene expression in Brassica napus. The Ti plasmid inducible gene transfer system was used for MLC chimeric recombinant gene expression in B. napus. Gene expression was confirmed by polymerase chain reaction (PCR), beta-glucuronidase reporter gene (GUS) assay, and Western blot. RESULTS: The MLC chimeric recombinant protein expressed in B. napus had a molecular weight of approximately 25 kDa. It exhibited a clinical sensitivity of 84.21% (n = 38) and a clinical specificity of 100% (n = 24) as assessed by enzyme-linked immunosorbent assay (ELISA). Oral immunization of BALB/c mice with MLC chimeric recombinant protein successfully induced antigen-specific IgG1 production. Additionally, the Th1-related cytokines IL-12 (p40), TNF, and IFN-γ were significantly increased in the spleens of the BALB/c mice. CONCLUSIONS: The chimeric MLC recombinant protein produced in B. napus has potential as both as an antigen for diagnosis and as a valuable vaccine candidate for oral immunization against vivax malaria.",2011 Apr 29,"['Lee, Choonghee', 'Kim, Hyung-Hwan', 'Mi Choi, Kyung', 'Won Chung, Kyung', 'Choi, Yien Kyoung', 'Jang, Mi Jung', 'Kim, Tong-Soo', 'Chung, Nam-Jun', 'Rhie, Ho-Gun', 'Lee, Ho-Sa', 'Sohn, Youngjoo', 'Kim, Hyuck', 'Lee, Sung-Jae', 'Lee, Hyeong-Woo']",Malar J,,,True
0638a299934da797243f6f35a516e172a38466a4,PMC,Diffuse Alveolar Damage: A Common Phenomenon in Progressive Interstitial Lung Disorders,http://dx.doi.org/10.1155/2011/531302,PMC3099744,21637367,CC BY,"It has become obvious that several interstitial lung diseases, and even viral lung infections, can progress rapidly, and exhibit similar features in their lung morphology. The final histopathological feature, common in these lung disorders, is diffuse alveolar damage (DAD). The histopathology of DAD is considered to represent end stage phenomenon in acutely behaving interstitial pneumonias, such as acute interstitial pneumonia (AIP) and acute exacerbations of idiopathic pulmonary fibrosis (IPF). Acute worsening and DAD may occur also in patients with nonspecific interstitial pneumonias (NSIPs), and even in severe viral lung infections where there is DAD histopathology in the lung. A better understanding of the mechanisms underlying the DAD reaction is needed to clarify the treatment for these serious lung diseases. There is an urgent need for international efforts for studying DAD-associated lung diseases, since the prognosis of these patients has been and is still dismal.",2011 Nov 2,"['Kaarteenaho, Riitta', 'Kinnula, Vuokko L.']",Pulm Med,,,True
aec923adf0e16d218315a3083aaa71fb9ddb8b39,PMC,Temporal Anomalies in Immunological Gene Expression in a Time Series of Wild Mice: Signature of an Epidemic?,http://dx.doi.org/10.1371/journal.pone.0020070,PMC3100328,21629775,CC BY,"Although the ecological importance of coinfection is increasingly recognized, analyses of microbial pathogen dynamics in wildlife usually focus on an ad hoc subset of the species present due to technological limitations on detection. Here we demonstrate the use of expression profiles for immunological genes (pattern recognition receptors, cytokines and transcription factors) as a means to identify, without preconception, the likelihood of important acute microbial infections in wildlife. Using a wood mouse population in the UK as a model we identified significant temporal clusters of individuals with extreme expression of immunological mediators across multiple loci, typical of an acute microbial infection. These clusters were circumstantially associated with demographic perturbation in the summertime wood mouse population. Animals in one cluster also had significantly higher individual macroparasite burdens than contemporaries with “normal” expression patterns. If the extreme transcriptional profiles observed are induced by an infectious agent then this implicates macroparasites as a possible player in mediating individual susceptibility or resilience to infection. The form of survey described here, combined with next generation nucleic acids sequencing methods for the broad detection of microbial infectious agents in individuals with anomalous immunological transcriptional profiles, could be a powerful tool for revealing unrecognized, ecologically important infectious agents circulating in wildlife populations.",2011 May 23,"['Friberg, Ida M.', 'Lowe, Ann', 'Ralli, Catriona', 'Bradley, Janette E.', 'Jackson, Joseph A.']",PLoS One,,,True
06d734de60efb9ac8c98cd02be9f667d0c535fb0,PMC,Propagation of Respiratory Aerosols by the Vuvuzela,http://dx.doi.org/10.1371/journal.pone.0020086,PMC3100331,21629778,CC BY,"Vuvuzelas, the plastic blowing horns used by sports fans, recently achieved international recognition during the FIFA World Cup soccer tournament in South Africa. We hypothesised that vuvuzelas might facilitate the generation and dissemination of respiratory aerosols. To investigate the quantity and size of aerosols emitted when the instrument is played, eight healthy volunteers were asked to blow a vuvuzela. For each individual the concentration of particles in expelled air was measured using a six channel laser particle counter and the duration of blowing and velocity of air leaving the vuvuzela were recorded. To allow comparison with other activities undertaken at sports events each individual was also asked to shout and the measurements were repeated while using a paper cone to confine the exhaled air. Triplicate measurements were taken for each individual. The mean peak particle counts were 658×10(3) per litre for the vuvuzela and 3.7×10(3) per litre for shouting, representing a mean log(10) difference of 2.20 (95% CI: 2.03,2.36; p<0.001). The majority (>97%) of particles captured from either the vuvuzela or shouting were between 0.5 and 5 microns in diameter. Mean peak airflows recorded for the vuvuzela and shouting were 6.1 and 1.8 litres per second respectively. We conclude that plastic blowing horns (vuvuzelas) have the capacity to propel extremely large numbers of aerosols into the atmosphere of a size able to penetrate the lower lung. Some respiratory pathogens are spread via contaminated aerosols emitted by infected persons. Further investigation is required to assess the potential of the vuvuzela to contribute to the transmission of aerosol borne diseases. We recommend, as a precautionary measure, that people with respiratory infections should be advised not to blow their vuvuzela in enclosed spaces and where there is a risk of infecting others.",2011 May 23,"['Lai, Ka-Man', 'Bottomley, Christian', 'McNerney, Ruth']",PLoS One,,,True
049d68aa5279d807e4125c33a3d563f6df987cb4,PMC,Gradual Increase of High Mobility Group Protein B1 in the Lungs after the Onset of Acute Exacerbation of Idiopathic Pulmonary Fibrosis,http://dx.doi.org/10.1155/2011/916486,PMC3100576,21637372,CC BY,"The pathogenesis of acute exacerbation of idiopathic pulmonary fibrosis (IPF) remains to be elucidated. To evaluate the roles of inflammatory mediators in acute exacerbation, the concentrations of high mobility group protein B1 (HMGB1), a chief mediator of acute lung injury, and 18 inflammatory cytokines were measured in the bronchoalveolar lavage fluid, serially sampled from seven IPF patients after the onset of acute exacerbation. HMGB1 gradually increased in the alveolar fluid after the onset of acute exacerbation, in positive correlation with monocytes chemotactic protein-1 (MCP-1), a potent fibrogenic mediator. In the lung tissues of eight IPF patients autopsied after acute exacerbation, intense cytoplasmic staining for HMGB1 was observed in the alveolar epithelial cells in alveolar capillary augmented lesions, where the capillary endothelial cells remarkably reduced the expression of thrombomodulin, an intrinsic antagonist of HMGB1. These results suggest pathogenic roles for HMGB1 and MCP-1 in the late phase of acute exacerbation of IPF.",2011 Feb 21,"['Ebina, Masahito', 'Taniguchi, Hiroyuki', 'Miyasho, Taku', 'Yamada, Shingo', 'Shibata, Naoko', 'Ohta, Hiromitsu', 'Hisata, Shu', 'Ohkouchi, Shinya', 'Tamada, Tsutomu', 'Nishimura, Hidekazu', 'Ishizaka, Akitoshi', 'Maruyama, Ikuro', 'Okada, Yoshinori', 'Takashi, Kondo', 'Nukiwa, Toshihiro']",Pulm Med,,,True
38d4184fcc07afbf2bd269491da88687764e86f0,PMC,Protein Microarrays and Biomarkers of Infectious Disease,http://dx.doi.org/10.3390/ijms11125165,PMC3100839,21614200,CC BY,"Protein microarrays are powerful tools that are widely used in systems biology research. For infectious diseases, proteome microarrays assembled from proteins of pathogens will play an increasingly important role in discovery of diagnostic markers, vaccines, and therapeutics. Distinct formats of protein microarrays have been developed for different applications, including abundance-based and function-based methods. Depending on the application, design issues should be considered, such as the need for multiplexing and label or label free detection methods. New developments, challenges, and future demands in infectious disease research will impact the application of protein microarrays for discovery and validation of biomarkers.",2010 Dec 16,"['Natesan, Mohan', 'Ulrich, Robert G.']",Int J Mol Sci,,,True
94a4251b88b47417be1ebffe98259c1d4c1e0b36,PMC,"Spliced Leader RNAs, Mitochondrial Gene Frameshifts and Multi-Protein Phylogeny Expand Support for the Genus Perkinsus as a Unique Group of Alveolates",http://dx.doi.org/10.1371/journal.pone.0019933,PMC3101222,21629701,CC BY,"The genus Perkinsus occupies a precarious phylogenetic position. To gain a better understanding of the relationship between perkinsids, dinoflagellates and other alveolates, we analyzed the nuclear-encoded spliced-leader (SL) RNA and mitochondrial genes, intron prevalence, and multi-protein phylogenies. In contrast to the canonical 22-nt SL found in dinoflagellates (DinoSL), P. marinus has a shorter (21-nt) and a longer (22-nt) SL with slightly different sequences than DinoSL. The major SL RNA transcripts range in size between 80–83 nt in P. marinus, and ∼83 nt in P. chesapeaki, significantly larger than the typical ≤56-nt dinoflagellate SL RNA. In most of the phylogenetic trees based on 41 predicted protein sequences, P. marinus branched at the base of the dinoflagellate clade that included the ancient taxa Oxyrrhis and Amoebophrya, sister to the clade of apicomplexans, and in some cases clustered with apicomplexans as a sister to the dinoflagellate clade. Of 104 Perkinsus spp. genes examined 69.2% had introns, a higher intron prevalence than in dinoflagellates. Examination of Perkinsus spp. mitochondrial cytochrome B and cytochrome C oxidase subunit I genes and their cDNAs revealed no mRNA editing, but these transcripts can only be translated when frameshifts are introduced at every AGG and CCC codon as if AGGY codes for glycine and CCCCU for proline. These results, along with the presence of the numerous uncharacterized ‘marine alveolate group I' and Perkinsus-like lineages separating perkinsids from core dinoflagellates, expand support for the affiliation of the genus Perkinsus with an independent lineage (Perkinsozoa) positioned between the phyla of Apicomplexa and Dinoflagellata.",2011 May 24,"['Zhang, Huan', 'Campbell, David A.', 'Sturm, Nancy R.', 'Dungan, Christopher F.', 'Lin, Senjie']",PLoS One,,,True
e65736745475f7a3bab0f310edb593acc50528b7,PMC,Crystal Structure and Functional Analysis of the SARS-Coronavirus RNA Cap 2′-O-Methyltransferase nsp10/nsp16 Complex,http://dx.doi.org/10.1371/journal.ppat.1002059,PMC3102710,21637813,CC BY,"Cellular and viral S-adenosylmethionine-dependent methyltransferases are involved in many regulated processes such as metabolism, detoxification, signal transduction, chromatin remodeling, nucleic acid processing, and mRNA capping. The Severe Acute Respiratory Syndrome coronavirus nsp16 protein is a S-adenosylmethionine-dependent (nucleoside-2′-O)-methyltransferase only active in the presence of its activating partner nsp10. We report the nsp10/nsp16 complex structure at 2.0 Å resolution, which shows nsp10 bound to nsp16 through a ∼930 Å(2) surface area in nsp10. Functional assays identify key residues involved in nsp10/nsp16 association, and in RNA binding or catalysis, the latter likely through a SN2-like mechanism. We present two other crystal structures, the inhibitor Sinefungin bound in the S-adenosylmethionine binding pocket and the tighter complex nsp10(Y96F)/nsp16, providing the first structural insight into the regulation of RNA capping enzymes in (+)RNA viruses.",2011 May 26,"['Decroly, Etienne', 'Debarnot, Claire', 'Ferron, François', 'Bouvet, Mickael', 'Coutard, Bruno', 'Imbert, Isabelle', 'Gluais, Laure', 'Papageorgiou, Nicolas', 'Sharff, Andrew', 'Bricogne, Gérard', 'Ortiz-Lombardia, Miguel', 'Lescar, Julien', 'Canard, Bruno']",PLoS Pathog,,,True
e88b28b3664d30889a0161ddee188c48897a3bee,PMC,"SARS-CoV 9b Protein Diffuses into Nucleus, Undergoes Active Crm1 Mediated Nucleocytoplasmic Export and Triggers Apoptosis When Retained in the Nucleus",http://dx.doi.org/10.1371/journal.pone.0019436,PMC3103500,21637748,CC BY,"BACKGROUND: 9b is an accessory protein of the SARS-CoV. It is a small protein of 98 amino acids and its structure has been solved recently. 9b is known to localize in the extra-nuclear region and has been postulated to possess a nuclear export signal (NES), however the role of NES in 9b functioning is not well understood. PRINCIPAL FINDINGS/METHODOLOGY: In this report, we demonstrate that 9b in the absence of any nuclear localization signal (NLS) enters the nucleus by passive transport. Using various cell cycle inhibitors, we have shown that the nuclear entry of 9b is independent of the cell cycle. Further, we found that 9b interacts with the cellular protein Crm1 and gets exported out of the nucleus using an active NES. We have also revealed that this NES activity influences the half-life of 9b and affects host cell death. We found that an export signal deficient SARS-CoV 9b protein induces apoptosis in transiently transfected cells and showed elevated caspase-3 activity. CONCLUSION/SIGNIFICANCE: Here, we showed that nuclear shuttling of 9b and its interaction with Crm1 are essential for the proper degradation of 9b and blocking the nuclear export of this protein induces apoptosis. This phenomenon may be critical in providing a novel role to the 9b accessory protein of SARS-CoV.",2011 May 27,"['Sharma, Kulbhushan', 'Åkerström, Sara', 'Sharma, Anuj Kumar', 'Chow, Vincent T. K.', 'Teow, Shumein', 'Abrenica, Bernard', 'Booth, Stephanie A.', 'Booth, Timothy F.', 'Mirazimi, Ali', 'Lal, Sunil K.']",PLoS One,,,True
4ca552dd7e18609e57226f02001bf51bec3000bb,PMC,A New Approach to Monitoring Dengue Activity,http://dx.doi.org/10.1371/journal.pntd.0001215,PMC3104030,21647309,CC0,,2011 May 31,"['Madoff, Lawrence C.', 'Fisman, David N.', 'Kass-Hout, Taha']",PLoS Negl Trop Dis,,,True
db493d400b682be0385bd1ff034fa718d0c398cb,PMC,Maternal Influenza Immunization and Reduced Likelihood of Prematurity and Small for Gestational Age Births: A Retrospective Cohort Study,http://dx.doi.org/10.1371/journal.pmed.1000441,PMC3104979,21655318,CC BY,"BACKGROUND: Infections during pregnancy have the potential to adversely impact birth outcomes. We evaluated the association between receipt of inactivated influenza vaccine during pregnancy and prematurity and small for gestational age (SGA) births. METHODS AND FINDINGS: We conducted a cohort analysis of surveillance data from the Georgia (United States) Pregnancy Risk Assessment Monitoring System. Among 4,326 live births between 1 June 2004 and 30 September 2006, maternal influenza vaccine information was available for 4,168 (96.3%). The primary intervention evaluated in this study was receipt of influenza vaccine during any trimester of pregnancy. The main outcome measures were prematurity (gestational age at birth <37 wk) and SGA (birth weight <10th percentile for gestational age). Infants who were born during the putative influenza season (1 October–31 May) and whose mothers were vaccinated against influenza during pregnancy were less likely to be premature compared to infants of unvaccinated mothers born in the same period (adjusted odds ratio [OR] = 0.60; 95% CI, 0.38–0.94). The magnitude of association between maternal influenza vaccine receipt and reduced likelihood of prematurity increased during the period of at least local influenza activity (adjusted OR = 0.44; 95% CI, 0.26–0.73) and was greatest during the widespread influenza activity period (adjusted OR = 0.28; 95% CI, 0.11–0.74). Compared with newborns of unvaccinated women, newborns of vaccinated mothers had 69% lower odds of being SGA (adjusted OR = 0.31; 95% CI, 0.13–0.75) during the period of widespread influenza activity. The adjusted and unadjusted ORs were not significant for the pre-influenza activity period. CONCLUSIONS: This study demonstrates an association between immunization with the inactivated influenza vaccine during pregnancy and reduced likelihood of prematurity during local, regional, and widespread influenza activity periods. However, no associations were found for the pre-influenza activity period. Moreover, during the period of widespread influenza activity there was an association between maternal receipt of influenza vaccine and reduced likelihood of SGA birth. Please see later in the article for the Editors' Summary",2011 May 31,"['Omer, Saad B.', 'Goodman, David', 'Steinhoff, Mark C.', 'Rochat, Roger', 'Klugman, Keith P.', 'Stoll, Barbara J.', 'Ramakrishnan, Usha']",PLoS Med,,,True
a3bd2c7d348548cb21d4e9f4eb63ac51ea015e10,PMC,"Access to a polymerase chain reaction assay method targeting 13 respiratory viruses can reduce antibiotics: a randomised, controlled trial",http://dx.doi.org/10.1186/1741-7015-9-44,PMC3108322,21521505,CC BY,"BACKGROUND: Viral respiratory infections are common worldwide and range from completely benign disease to life-threatening illness. Symptoms can be unspecific, and an etiologic diagnosis is rarely established because of a lack of suitable diagnostic tools. Improper use of antibiotics is common in this setting, which is detrimental in light of the development of bacterial resistance. It has been suggested that the use of diagnostic tests could reduce antibiotic prescription rates. The objective of this study was to evaluate whether access to a multiplex polymerase chain reaction (PCR) assay panel for etiologic diagnosis of acute respiratory tract infections (ARTIs) would have an impact on antibiotic prescription rate in primary care clinical settings. METHODS: Adult patients with symptoms of ARTI were prospectively included. Nasopharyngeal and throat swabs were analysed by using a multiplex real-time PCR method targeting thirteen viruses and two bacteria. Patients were recruited at 12 outpatient units from October 2006 through April 2009, and samples were collected on the day of inclusion (initial visit) and after 10 days (follow-up visit). Patients were randomised in an open-label treatment protocol to receive a rapid or delayed result (on the following day or after eight to twelve days). The primary outcome measure was the antibiotic prescription rate at the initial visit, and the secondary outcome was the total antibiotic prescription rate during the study period. RESULTS: A total sample of 447 patients was randomised. Forty-one were excluded, leaving 406 patients for analysis. In the group of patients randomised for a rapid result, 4.5% (9 of 202) of patients received antibiotics at the initial visit, compared to 12.3% (25 of 204) (P = 0.005) of patients in the delayed result group. At follow-up, there was no significant difference between the groups: 13.9% (28 of 202) in the rapid result group and 17.2% (35 of 204) in the delayed result group (P = 0.359), respectively. CONCLUSIONS: Access to a rapid method for etiologic diagnosis of ARTIs may reduce antibiotic prescription rates at the initial visit in an outpatient setting. To sustain this effect, however, it seems necessary to better define how to follow and manage the patient according to the result of the test, which warrants further investigation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01133782.",2011 Apr 26,"['Brittain-Long, Robin', 'Westin, Johan', 'Olofsson, Sigvard', 'Lindh, Magnus', 'Andersson, Lars-Magnus']",BMC Med,,,True
3acb357dc20a411ef495ab53d242e5a0454cd1fb,PMC,Standardization of Methods for Early Diagnosis and On-Site Treatment of High-Altitude Pulmonary Edema,http://dx.doi.org/10.1155/2011/190648,PMC3109313,21660284,CC BY,"High-altitude pulmonary edema (HAPE) is a life-threatening disease of high altitude that often affects nonacclimatized apparently healthy individuals who rapidly ascend to high altitude. Early detection, early diagnosis, and early treatment are essential to maintain the safety of people who ascend to high altitude, such as construction workers and tourists. In this paper, I discuss various methods and criteria that can be used for the early diagnosis and prediction of HAPE. I also discuss the preventive strategies and options for on-site treatment. My objective is to improve the understanding of HAPE and to highlight the need for prevention, early diagnosis, and early treatment of HAPE to improve the safety of individuals ascending to high altitude.",2011 Jun 1,"Zhou, Qiquan",Pulm Med,,,True
c4127920bfadc5eaa2ff7d2180f8e1de7e3a673a,PMC,"Temporal Analysis of the Honey Bee Microbiome Reveals Four Novel Viruses and Seasonal Prevalence of Known Viruses, Nosema, and Crithidia",http://dx.doi.org/10.1371/journal.pone.0020656,PMC3110205,21687739,CC BY,"Honey bees (Apis mellifera) play a critical role in global food production as pollinators of numerous crops. Recently, honey bee populations in the United States, Canada, and Europe have suffered an unexplained increase in annual losses due to a phenomenon known as Colony Collapse Disorder (CCD). Epidemiological analysis of CCD is confounded by a relative dearth of bee pathogen field studies. To identify what constitutes an abnormal pathophysiological condition in a honey bee colony, it is critical to have characterized the spectrum of exogenous infectious agents in healthy hives over time. We conducted a prospective study of a large scale migratory bee keeping operation using high-frequency sampling paired with comprehensive molecular detection methods, including a custom microarray, qPCR, and ultra deep sequencing. We established seasonal incidence and abundance of known viruses, Nosema sp., Crithidia mellificae, and bacteria. Ultra deep sequence analysis further identified four novel RNA viruses, two of which were the most abundant observed components of the honey bee microbiome (∼10(11) viruses per honey bee). Our results demonstrate episodic viral incidence and distinct pathogen patterns between summer and winter time-points. Peak infection of common honey bee viruses and Nosema occurred in the summer, whereas levels of the trypanosomatid Crithidia mellificae and Lake Sinai virus 2, a novel virus, peaked in January.",2011 Jun 7,"['Runckel, Charles', 'Flenniken, Michelle L.', 'Engel, Juan C.', 'Ruby, J. Graham', 'Ganem, Donald', 'Andino, Raul', 'DeRisi, Joseph L.']",PLoS One,,,True
0c0806be80c60f0e61f084f12ed847c265fc1d68,PMC,Evaluation of Coseasonality of Influenza and Invasive Pneumococcal Disease: Results from Prospective Surveillance,http://dx.doi.org/10.1371/journal.pmed.1001042,PMC3110256,21687693,CC BY,"BACKGROUND: The wintertime co-occurrence of peaks in influenza and invasive pneumococcal disease (IPD) is well documented, but how and whether wintertime peaks caused by these two pathogens are causally related is still uncertain. We aimed to investigate the relationship between influenza infection and IPD in Ontario, Canada, using several complementary methodological tools. METHODS AND FINDINGS: We evaluated a total number of 38,501 positive influenza tests in Central Ontario and 6,191 episodes of IPD in the Toronto/Peel area, Ontario, Canada, between 1 January 1995 and 3 October 2009, reported through population-based surveillance. We assessed the relationship between the seasonal wave forms for influenza and IPD using fast Fourier transforms in order to examine the relationship between these two pathogens over yearly timescales. We also used three complementary statistical methods (time-series methods, negative binomial regression, and case-crossover methods) to evaluate the short-term effect of influenza dynamics on pneumococcal risk. Annual periodicity with wintertime peaks could be demonstrated for IPD, whereas periodicity for influenza was less regular. As for long-term effects, phase and amplitude terms of pneumococcal and influenza seasonal sine waves were not correlated and meta-analysis confirmed significant heterogeneity of influenza, but not pneumococcal phase terms. In contrast, influenza was shown to Granger-cause pneumococcal disease. A short-term association between IPD and influenza could be demonstrated for 1-week lags in both case-crossover (odds ratio [95% confidence interval] for one case of IPD per 100 influenza cases  = 1.10 [1.02–1.18]) and negative binomial regression analysis (incidence rate ratio [95% confidence interval] for one case of IPD per 100 influenza cases  = 1.09 [1.05–1.14]). CONCLUSIONS: Our data support the hypothesis that influenza influences bacterial disease incidence by enhancing short-term risk of invasion in colonized individuals. The absence of correlation between seasonal waveforms, on the other hand, suggests that bacterial disease transmission is affected to a lesser extent. Please see later in the article for the Editors' Summary",2011 Jun 7,"['Kuster, Stefan P.', 'Tuite, Ashleigh R.', 'Kwong, Jeffrey C.', 'McGeer, Allison', None, 'Fisman, David N.']",PLoS Med,,,True
6bf7eb57bcb46ac71e49305ef93f2acafc869e9b,PMC,The Pathogenesis of Rift Valley Fever,http://dx.doi.org/10.3390/v3050493,PMC3111045,21666766,CC BY,"Rift Valley fever (RVF) is an emerging zoonotic disease distributed in sub-Saharan African countries and the Arabian Peninsula. The disease is caused by the Rift Valley fever virus (RVFV) of the family Bunyaviridae and the genus Phlebovirus. The virus is transmitted by mosquitoes, and virus replication in domestic ruminant results in high rates of mortality and abortion. RVFV infection in humans usually causes a self-limiting, acute and febrile illness; however, a small number of cases progress to neurological disorders, partial or complete blindness, hemorrhagic fever, or thrombosis. This review describes the pathology of RVF in human patients and several animal models, and summarizes the role of viral virulence factors and host factors that affect RVFV pathogenesis.",2011 May 6,"['Ikegami, Tetsuro', 'Makino, Shinji']",Viruses,,,True
ebe8d3845bdfbc11f865667d68399c4862551d30,PMC,Coronavirus Gene 7 Counteracts Host Defenses and Modulates Virus Virulence,http://dx.doi.org/10.1371/journal.ppat.1002090,PMC3111541,21695242,CC BY,"Transmissible gastroenteritis virus (TGEV) genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7). Both the mutant and the parental (rTGEV-wt) viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α) phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c), a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the acquisition of gene 7 by the TGEV genome most likely has provided a selective advantage to the virus.",2011 Jun 9,"['Cruz, Jazmina L. G.', 'Sola, Isabel', 'Becares, Martina', 'Alberca, Berta', 'Plana, Joan', 'Enjuanes, Luis', 'Zuñiga, Sonia']",PLoS Pathog,,,True
fe954b75ed45c02d47090ee70d25c726b24b081c,PMC,"Knowledge, Attitudes and Practices (KAP) related to the Pandemic (H1N1) 2009 among Chinese General Population: a Telephone Survey",http://dx.doi.org/10.1186/1471-2334-11-128,PMC3112099,21575222,CC BY,"BACKGROUND: China is at greatest risk of the Pandemic (H1N1) 2009 due to its huge population and high residential density. The unclear comprehension and negative attitudes towards the emerging infectious disease among general population may lead to unnecessary worry and even panic. The objective of this study was to investigate the Chinese public response to H1N1 pandemic and provide baseline data to develop public education campaigns in response to future outbreaks. METHODS: A close-ended questionnaire developed by the Chinese Center for Disease Control and Prevention was applied to assess the knowledge, attitudes and practices (KAP) of pandemic (H1N1) 2009 among 10,669 responders recruited from seven urban and two rural areas of China sampled by using the probability proportional to size (PPS) method. RESULTS: 30.0% respondents were not clear whether food spread H1N1 virusand. 65.7% reported that the pandemic had no impact on their life. The immunization rates of the seasonal flu and H1N1vaccine were 7.5% and 10.8%, respectively. Farmers and those with lower education level were less likely to know the main transmission route (cough or talk face to face). Female and those with college and above education had higher perception of risk and more compliance with preventive behaviors. Relationships between knowledge and risk perception (OR = 1.69; 95%CI 1.54-1.86), and knowledge and practices (OR = 1.57; 95%CI 1.42-1.73) were found among the study subjects. With regard to the behavior of taking up A/H1N1 vaccination, there are several related factors found in the current study population, including the perception of life disturbed (OR = 1.29; 95%CI 1.11-1.50), the safety of A/H1N1 vaccine (OR = 0.07; 95%CI 0.04-0.11), the knowledge of free vaccination policy (OR = 7.20; 95%CI 5.91-8.78), the state's priority vaccination strategy(OR = 1.33; 95%CI 1.08-1.64), and taking up seasonal influenza vaccine behavior (OR = 4.69; 95%CI 3.53-6.23). CONCLUSIONS: This A/H1N1 epidemic has not caused public panic yet, but the knowledge of A/H1N1 in residents is not optimistic. Public education campaign may take the side effects of vaccine and the knowledge about the state's vaccination strategy into account.",2011 May 16,"['Lin, Yilan', 'Huang, Lijuan', 'Nie, Shaofa', 'Liu, Zengyan', 'Yu, Hongjie', 'Yan, Weirong', 'Xu, Yihua']",BMC Infect Dis,,,True
e9b2d0e930a4e8ec960b5e4dc7e627b4d243ac0f,PMC,"Novel viral vectors utilizing intron splice-switching to activate genome rescue, expression and replication in targeted cells",http://dx.doi.org/10.1186/1743-422X-8-243,PMC3113310,21595942,CC BY,"BACKGROUND: The outcome of virus infection depends from the precise coordination of viral gene expression and genome replication. The ability to control and regulate these processes is therefore important for analysis of infection process. Viruses are also useful tools in bio- and gene technology; they can efficiently kill cancer cells and trigger immune responses to tumors. However, the methods for constructing tissue- or cell-type specific viruses typically suffer from low target-cell specificity and a high risk of reversion. Therefore novel and universal methods of regulation of viral infection are also important for therapeutic application of virus-based systems. METHODS: Aberrantly spliced introns were introduced into crucial gene-expression units of adenovirus vector and alphavirus DNA/RNA layered vectors and their effects on the viral gene expression, replication and/or the release of infectious genomes were studied in cell culture. Transfection of the cells with splice-switching oligonucleotides was used to correct the introduced functional defect(s). RESULTS: It was demonstrated that viral gene expression, replication and/or the release of infectious genomes can be blocked by the introduction of aberrantly spliced introns. The insertion of such an intron into an adenovirus vector reduced the expression of the targeted gene more than fifty-fold. A similar insertion into an alphavirus DNA/RNA layered vector had a less dramatic effect; here, only the release of the infectious transcript was suppressed but not the subsequent replication and spread of the virus. However the insertion of two aberrantly spliced introns resulted in an over one hundred-fold reduction in the infectivity of the DNA/RNA layered vector. Furthermore, in both systems the observed effects could be reverted by the delivery of splice-switching oligonucleotide(s), which corrected the splicing defects. CONCLUSIONS: Splice-switch technology, originally developed for genetic disease therapy, can also be used to control gene expression of viral vectors. This approach represents a novel, universal and powerful method for controlling gene expression, replication, viral spread and, by extension, virus-induced cytotoxic effects and can be used both for basic studies of virus infection and in virus-based gene- and anti-cancer therapy.",2011 May 19,"['Viru, Liane', 'Heller, Gregory', 'Lehto, Taavi', 'Pärn, Kalle', 'El Andaloussi, Samir', 'Langel, Ülo', 'Merits, Andres']",Virol J,,,True
4481ddf0d81e186b0be8ab48c20e8b206ec2879c,PMC,Non-Apical Membrane Antigen 1 (AMA1) IgGs from Malian Children Interfere with Functional Activity of AMA1 IgGs as Judged by Growth Inhibition Assay,http://dx.doi.org/10.1371/journal.pone.0020947,PMC3113848,21695140,CC0,"BACKGROUND: Apical membrane antigen 1 (AMA1) is one of the best-studied blood-stage malaria vaccine candidates. When an AMA1 vaccine was tested in a malaria naïve population, it induced functionally active antibodies judged by Growth Inhibition Assay (GIA). However, the same vaccine failed to induce higher growth-inhibitory activity in adults living in a malaria endemic area. Vaccination did induce functionally active antibodies in malaria-exposed children with less than 20% inhibition in GIA at baseline, but not in children with more than that level of baseline inhibition. METHODS: Total IgGs were purified from plasmas collected from the pediatric trial before and after immunization and pools of total IgGs were made. Another set of total IgGs was purified from U.S. adults immunized with AMA1 (US-total IgG). From these total IgGs, AMA1-specific and non-AMA1 IgGs were affinity purified and the functional activity of these IgGs was evaluated by GIA. Competition ELISA was performed with the U.S.-total IgG and non-AMA1 IgGs from malaria-exposed children. RESULTS: AMA1-specific IgGs from malaria-exposed children and U.S. vaccinees showed similar growth-inhibitory activity at the same concentrations. When mixed with U.S.-total IgG, non-AMA1 IgGs from children showed an interference effect in GIA. Interestingly, the interference effect was higher with non-AMA1 IgGs from higher titer pools. The non-AMA1 IgGs did not compete with anti-AMA1 antibody in U.S.-total IgG in the competition ELISA. CONCLUSION: Children living in a malaria endemic area have a fraction of IgGs that interferes with the biological activity of anti-AMA1 antibody as judged by GIA. While the mechanism of interference is not resolved in this study, these results suggest it is not caused by direct competition between non-AMA1 IgG and AMA1 protein. This study indicates that anti-malaria IgGs induced by natural exposure may interfere with the biological effect of antibody induced by an AMA1-based vaccine in the target population.",2011 Jun 13,"['Miura, Kazutoyo', 'Perera, Suwani', 'Brockley, Sarah', 'Zhou, Hong', 'Aebig, Joan A.', 'Moretz, Samuel E.', 'Miller, Louis H.', 'Doumbo, Ogobara K.', 'Sagara, Issaka', 'Dicko, Alassane', 'Ellis, Ruth D.', 'Long, Carole A.']",PLoS One,,,True
2d32032f8498219617634b8b4e5f5c7d214d2ebb,PMC,The usefulness of case reports in managing emerging infectious disease,http://dx.doi.org/10.1186/1752-1947-5-194,PMC3113999,21599907,CC BY,"Emerging infectious diseases are an important problem in medicine. Case reports usually document episodes in the early emerging phase or in a small outbreak. Although the case report is considered weak evidence in medical literature, it is usually the first report when there is a new emerging infectious disease. There is no doubt that case reports can provide useful information for further case series, reviews and studies. This editorial focuses on the usefulness of the case report on emerging infectious disease to the medical society. Publication in this area is highly welcomed by the journal and can serve as a future point of reference.",2011 May 20,"Wiwanitkit, Viroj",J Med Case Reports,,,True
8866d2274d3ecb0ef50ccf806d9e03839ad2edbc,PMC,PCR Improves Diagnostic Yield from Lung Aspiration in Malawian Children with Radiologically Confirmed Pneumonia,http://dx.doi.org/10.1371/journal.pone.0021042,PMC3114850,21695128,CC BY,"BACKGROUND: Accurate data on childhood pneumonia aetiology are essential especially from regions where mortality is high, in order to inform case-management guidelines and the potential of prevention strategies such as bacterial conjugate vaccines. Yield from blood culture is low, but lung aspirate culture provides a higher diagnostic yield. We aimed to determine if diagnostic yield could be increased further by polymerase chain reaction (PCR) detection of bacteria (Streptococcus pneumoniae and Haemophilus influenzae b) and viruses in lung aspirate fluid. METHODS: A total of 95 children with radiological focal, lobar or segmental consolidation had lung aspirate performed and sent for bacterial culture and for PCR for detection of bacteria, viruses and Pneumocystis jirovecii. In children with a pneumococcal aetiology, pneumococcal bacterial loads were calculated in blood and lung aspirate fluid. RESULTS: Blood culture identified a bacterial pathogen in only 8 patients (8%). With the addition of PCR on lung aspirate samples, causative pathogens (bacterial, viral, pneumocystis) were identified singly or as co-infections in 59 children (62%). The commonest bacterial organism was S.pneumoniae (41%), followed by H. influenzae b (6%), and the commonest virus identified was adenovirus (16%), followed by human bocavirus (HBoV) (4%), either as single or co-infection. CONCLUSIONS: In a select group of African children, lung aspirate PCR significantly improves diagnostic yield. Our study confirms a major role of S.pneumoniae and viruses in the aetiology of childhood pneumonia in Africa.",2011 Jun 14,"['Carrol, Enitan D.', 'Mankhambo, Limangeni A.', 'Guiver, Malcolm', 'Banda, Daniel L.', None, 'Denis, Brigitte', 'Dove, Winifred', 'Jeffers, Graham', 'Molyneux, Elizabeth M.', 'Molyneux, Malcolm E.', 'Hart, C. Anthony', 'Graham, Stephen M.']",PLoS One,,,True
93b3fcce1e0a7c9a82091bd832b1b3a286133679,PMC,Influenza A Virus Nucleoprotein Exploits Hsp40 to Inhibit PKR Activation,http://dx.doi.org/10.1371/journal.pone.0020215,PMC3115951,21698289,CC0,"BACKGROUND: Double-stranded RNA dependent protein kinase (PKR) is a key regulator of the anti-viral innate immune response in mammalian cells. PKR activity is regulated by a 58 kilo Dalton cellular inhibitor (P58(IPK)), which is present in inactive state as a complex with Hsp40 under normal conditions. In case of influenza A virus (IAV) infection, P58(IPK) is known to dissociate from Hsp40 and inhibit PKR activation. However the influenza virus component responsible for PKR inhibition through P58(IPK) activation was hitherto unknown. PRINCIPAL FINDINGS: Human heat shock 40 protein (Hsp40) was identified as an interacting partner of Influenza A virus nucleoprotein (IAV NP) using a yeast two-hybrid screen. This interaction was confirmed by co-immunoprecipitation studies from mammalian cells transfected with IAV NP expressing plasmid. Further, the IAV NP-Hsp40 interaction was validated in mammalian cells infected with various seasonal and pandemic strains of influenza viruses. Cellular localization studies showed that NP and Hsp40 co-localize primarily in the nucleus. During IAV infection in mammalian cells, expression of NP coincided with the dissociation of P58(IPK) from Hsp40 and decrease PKR phosphorylation. We observed that, plasmid based expression of NP in mammalian cells leads to decrease in PKR phosphorylation. Furthermore, inhibition of NP expression during influenza virus replication led to PKR activation and concomitant increase in eIF2α phosphorylation. Inhibition of NP expression also led to reduced IRF3 phosphorylation, enhanced IFN β production and concomitant reduction of virus replication. Taken together our data suggest that NP is the viral factor responsible for P58(IPK) activation and subsequent inhibition of PKR-mediated host response during IAV infection. SIGNIFICANCE: Our findings demonstrate a novel role of IAV NP in inhibiting PKR-mediated anti-viral host response and help us understand P58(IPK) mediated inhibition of PKR activity during IAV infection.",2011 Jun 15,"['Sharma, Kulbhushan', 'Tripathi, Shashank', 'Ranjan, Priya', 'Kumar, Purnima', 'Garten, Rebecca', 'Deyde, Varough', 'Katz, Jacqueline M.', 'Cox, Nancy J.', 'Lal, Renu B.', 'Sambhara, Suryaprakash', 'Lal, Sunil K.']",PLoS One,,,True
69ddca48a5d1e593fbd057160b100afb374276c8,PMC,Equine Torovirus (BEV) Induces Caspase-Mediated Apoptosis in Infected Cells,http://dx.doi.org/10.1371/journal.pone.0020972,PMC3115971,21698249,CC BY,"Toroviruses are gastroenteritis causing agents that infect different animal species and humans. To date, very little is known about how toroviruses cause disease. Here, we describe for the first time that the prototype member of this genus, the equine torovirus Berne virus (BEV), induces apoptosis in infected cells at late times postinfection. Observation of BEV infected cells by electron microscopy revealed that by 24 hours postinfection some cells exhibited morphological characteristics of apoptotic cells. Based on this finding, we analyzed several apoptotic markers, and observed protein synthesis inhibition, rRNA and DNA degradation, nuclear fragmentation, caspase-mediated cleavage of PARP and eIF4GI, and PKR and eIF2α phosphorylation, all these processes taking place after peak virus production. We also determined that both cell death receptor and mitochondrial pathways are involved in the apoptosis process induced by BEV. BEV-induced apoptosis at late times postinfection, once viral progeny are produced, could facilitate viral dissemination in vivo and contribute to viral pathogenesis.",2011 Jun 15,"['Maestre, Ana M.', 'Garzón, Ana', 'Rodríguez, Dolores']",PLoS One,,,True
621648da481a06d1a2bb80c56e998f7373215be6,PMC,Hepatitis B Virus Genotype G forms core-like particles with unique structural properties,http://dx.doi.org/10.1111/j.1365-2893.2010.01330.x,PMC3116152,20546498,CC BY,"SUMMARY: We have determined the structure of the core capsid of an unusual variant of hepatitis B virus, genotype G (HBV/G) at 14 Å resolution, using cryo-electron microscopy. The structure reveals surface features not present in the prototype HBV/A genotype. HBV/G is novel in that it has a unique 36- bp insertion downstream of the core gene start codon. This results in a twelve amino acid insertion at the N-terminal end of the core protein, and two stop codons in the precore region that prevent the expression of HBeAg. HBV/G replication in patients is associated with co-infection with another genotype of HBV, suggesting that HBV/G may have reduced replication efficiency in vivo. We localized the N-terminal insertion in HBV/G and show that it forms two additional masses on the core surface adjacent to each of the dimer-spikes and have modelled the structure of the additional residues within this density. We show that the position of the insertion would not interfere with translocation of nucleic acids through the pores to the core interior compartment. However, the insertion may partially obscure several residues on the core surface that are known to play a role in envelopment and secretion of virions, or that could affect structural rearrangements that may trigger envelopment after DNA second-strand synthesis.",2011 Jun,"['Cotelesage, J J H', 'Osiowy, C', 'Lawrence, C', 'deVarennes, S L', 'Teow, S', 'Beniac, D R', 'Booth, T F']",J Viral Hepat,,,True
bb01f3bd0a1b61ef92b556330b94f59c947ea1a9,PMC,A Functional Role for ADAM10 in Human Immunodeficiency Virus Type-1 Replication,http://dx.doi.org/10.1186/1742-4690-8-32,PMC3118345,21569301,CC BY,"BACKGROUND: Gene trap insertional mutagenesis was used as a high-throughput approach to discover cellular genes participating in viral infection by screening libraries of cells selected for survival from lytic infection with a variety of viruses. Cells harboring a disrupted ADAM10 (A Disintegrin and Metalloprotease 10) allele survived reovirus infection, and subsequently ADAM10 was shown by RNA interference to be important for replication of HIV-1. RESULTS: Silencing ADAM10 expression with small interfering RNA (siRNA) 48 hours before infection significantly inhibited HIV-1 replication in primary human monocyte-derived macrophages and in CD4(+ )cell lines. In agreement, ADAM10 over-expression significantly increased HIV-1 replication. ADAM10 down-regulation did not inhibit viral reverse transcription, indicating that viral entry and uncoating are also independent of ADAM10 expression. Integration of HIV-1 cDNA was reduced in ADAM10 down-regulated cells; however, concomitant 2-LTR circle formation was not detected, suggesting that HIV-1 does not enter the nucleus. Further, ADAM10 silencing inhibited downstream reporter gene expression and viral protein translation. Interestingly, we found that while the metalloprotease domain of ADAM10 is not required for HIV-1 replication, ADAM15 and γ-secretase (which proteolytically release the extracellular and intracellular domains of ADAM10 from the plasma membrane, respectively) do support productive infection. CONCLUSIONS: We propose that ADAM10 facilitates replication at the level of nuclear trafficking. Collectively, our data support a model whereby ADAM10 is cleaved by ADAM15 and γ-secretase and that the ADAM10 intracellular domain directly facilitates HIV-1 nuclear trafficking. Thus, ADAM10 represents a novel cellular target class for development of antiretroviral drugs.",2011 May 11,"['Friedrich, Brian M', 'Murray, James L', 'Li, Guangyu', 'Sheng, Jinsong', 'Hodge, Thomas W', 'Rubin, Donald H', ""O'Brien, William A"", 'Ferguson, Monique R']",Retrovirology,,,True
6c5521b73b11d4e229b4ca98f116bc32aa4052c3,PMC,Probing genomic diversity and evolution of Streptococcus suis serotype 2 by NimbleGen tiling arrays,http://dx.doi.org/10.1186/1471-2164-12-219,PMC3118785,21554741,CC BY,"BACKGROUND: Our previous studies revealed that a new disease form of streptococcal toxic shock syndrome (STSS) is associated with specific Streptococcus suis serotype 2 (SS2) strains. To achieve a better understanding of the pathogenicity and evolution of SS2 at the whole-genome level, comparative genomic analysis of 18 SS2 strains, selected on the basis of virulence and geographic origin, was performed using NimbleGen tiling arrays. RESULTS: Our results demonstrate that SS2 isolates have highly divergent genomes. The 89K pathogenicity island (PAI), which has been previously recognized as unique to the Chinese epidemic strains causing STSS, was partially included in some other virulent and avirulent strains. The ABC-type transport systems, encoded by 89K, were hypothesized to greatly contribute to the catastrophic features of STSS. Moreover, we identified many polymorphisms in genes encoding candidate or known virulence factors, such as PlcR, lipase, sortases, the pilus-associated proteins, and the response regulator RevS and CtsR. On the basis of analysis of regions of differences (RDs) across the entire genome for the 18 selected SS2 strains, a model of microevolution for these strains is proposed, which provides clues into Streptococcus pathogenicity and evolution. CONCLUSIONS: Our deep comparative genomic analysis of the 89K PAI present in the genome of SS2 strains revealed details into how some virulent strains acquired genes that may contribute to STSS, which may lead to better environmental monitoring of epidemic SS2 strains.",2011 May 10,"['Wu, Zuowei', 'Li, Ming', 'Wang, Changjun', 'Li, Jing', 'Lu, Na', 'Zhang, Ruifen', 'Jiang, Yongqiang', 'Yang, Ruifu', 'Liu, Cuihua', 'Liao, Hui', 'Gao, George F', 'Tang, Jiaqi', 'Zhu, Baoli']",BMC Genomics,,,True
cb76568fb12e6a9802c85a994def23156d29352b,PMC,Remote Data Retrieval for Bioinformatics Applications: An Agent Migration Approach,http://dx.doi.org/10.1371/journal.pone.0020949,PMC3119054,21701677,CC BY,"Some of the approaches have been developed to retrieve data automatically from one or multiple remote biological data sources. However, most of them require researchers to remain online and wait for returned results. The latter not only requires highly available network connection, but also may cause the network overload. Moreover, so far none of the existing approaches has been designed to address the following problems when retrieving the remote data in a mobile network environment: (1) the resources of mobile devices are limited; (2) network connection is relatively of low quality; and (3) mobile users are not always online. To address the aforementioned problems, we integrate an agent migration approach with a multi-agent system to overcome the high latency or limited bandwidth problem by moving their computations to the required resources or services. More importantly, the approach is fit for the mobile computing environments. Presented in this paper are also the system architecture, the migration strategy, as well as the security authentication of agent migration. As a demonstration, the remote data retrieval from GenBank was used to illustrate the feasibility of the proposed approach.",2011 Jun 20,"['Gao, Lei', 'Dai, Hua', 'Zhang, Tong-Liang', 'Chou, Kuo-Chen']",PLoS One,,,True
01e22956c79df3220a67bce71cf22de95d29b723,PMC,In-Depth Analysis of the Antibody Response of Individuals Exposed to Primary Dengue Virus Infection,http://dx.doi.org/10.1371/journal.pntd.0001188,PMC3119640,21713020,CC BY,"Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein). Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization.",2011 Jun 21,"['de Alwis, Ruklanthi', 'Beltramello, Martina', 'Messer, William B.', 'Sukupolvi-Petty, Soila', 'Wahala, Wahala M. P. B.', 'Kraus, Annette', 'Olivarez, Nicholas P.', 'Pham, Quang', 'Brian, James', 'Tsai, Wen-Yang', 'Wang, Wei-Kung', 'Halstead, Scott', 'Kliks, Srisakul', 'Diamond, Michael S.', 'Baric, Ralph', 'Lanzavecchia, Antonio', 'Sallusto, Federica', 'de Silva, Aravinda M.']",PLoS Negl Trop Dis,,,True
51b2c04a95156d66aec99817f2dc769566cace9d,PMC,Spatial and Temporal Characteristics of the 2009 A/H1N1 Influenza Pandemic in Peru,http://dx.doi.org/10.1371/journal.pone.0021287,PMC3119673,21712984,CC0,"BACKGROUND: Highly refined surveillance data on the 2009 A/H1N1 influenza pandemic are crucial to quantify the spatial and temporal characteristics of the pandemic. There is little information about the spatial-temporal dynamics of pandemic influenza in South America. Here we provide a quantitative description of the age-specific morbidity pandemic patterns across administrative areas of Peru. METHODS: We used daily cases of influenza-like-illness, tests for A/H1N1 influenza virus infections, and laboratory-confirmed A/H1N1 influenza cases reported to the epidemiological surveillance system of Peru's Ministry of Health from May 1 to December 31, 2009. We analyzed the geographic spread of the pandemic waves and their association with the winter school vacation period, demographic factors, and absolute humidity. We also estimated the reproduction number and quantified the association between the winter school vacation period and the age distribution of cases. RESULTS: The national pandemic curve revealed a bimodal winter pandemic wave, with the first peak limited to school age children in the Lima metropolitan area, and the second peak more geographically widespread. The reproduction number was estimated at 1.6–2.2 for the Lima metropolitan area and 1.3–1.5 in the rest of Peru. We found a significant association between the timing of the school vacation period and changes in the age distribution of cases, while earlier pandemic onset was correlated with large population size. By contrast there was no association between pandemic dynamics and absolute humidity. CONCLUSIONS: Our results indicate substantial spatial variation in pandemic patterns across Peru, with two pandemic waves of varying timing and impact by age and region. Moreover, the Peru data suggest a hierarchical transmission pattern of pandemic influenza A/H1N1 driven by large population centers. The higher reproduction number of the first pandemic wave could be explained by high contact rates among school-age children, the age group most affected during this early wave.",2011 Jun 21,"['Chowell, Gerardo', 'Viboud, Cécile', 'Munayco, Cesar V.', 'Gómez, Jorge', 'Simonsen, Lone', 'Miller, Mark A.', 'Tamerius, James', 'Fiestas, Victor', 'Halsey, Eric S.', 'Laguna-Torres, Victor A.']",PLoS One,,,True
7835feab0d31096fada1a14d10d67acc080a7d82,PMC,Rhinovirus Genome Variation during Chronic Upper and Lower Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.pone.0021163,PMC3119694,21713005,CC BY,"Routine screening of lung transplant recipients and hospital patients for respiratory virus infections allowed to identify human rhinovirus (HRV) in the upper and lower respiratory tracts, including immunocompromised hosts chronically infected with the same strain over weeks or months. Phylogenetic analysis of 144 HRV-positive samples showed no apparent correlation between a given viral genotype or species and their ability to invade the lower respiratory tract or lead to protracted infection. By contrast, protracted infections were found almost exclusively in immunocompromised patients, thus suggesting that host factors rather than the virus genotype modulate disease outcome, in particular the immune response. Complete genome sequencing of five chronic cases to study rhinovirus genome adaptation showed that the calculated mutation frequency was in the range observed during acute human infections. Analysis of mutation hot spot regions between specimens collected at different times or in different body sites revealed that non-synonymous changes were mostly concentrated in the viral capsid genes VP1, VP2 and VP3, independent of the HRV type. In an immunosuppressed lung transplant recipient infected with the same HRV strain for more than two years, both classical and ultra-deep sequencing of samples collected at different time points in the upper and lower respiratory tracts showed that these virus populations were phylogenetically indistinguishable over the course of infection, except for the last month. Specific signatures were found in the last two lower respiratory tract populations, including changes in the 5′UTR polypyrimidine tract and the VP2 immunogenic site 2. These results highlight for the first time the ability of a given rhinovirus to evolve in the course of a natural infection in immunocompromised patients and complement data obtained from previous experimental inoculation studies in immunocompetent volunteers.",2011 Jun 21,"['Tapparel, Caroline', 'Cordey, Samuel', 'Junier, Thomas', 'Farinelli, Laurent', 'Van Belle, Sandra', 'Soccal, Paola M.', 'Aubert, John-David', 'Zdobnov, Evgeny', 'Kaiser, Laurent']",PLoS One,,,True
de036403a12da2e18921c87a92cf8bcc67e9c051,PMC,Rhinovirus Genome Variation during Chronic Upper and Lower Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.pone.0021163,PMC3119694,21713005,CC BY,"Routine screening of lung transplant recipients and hospital patients for respiratory virus infections allowed to identify human rhinovirus (HRV) in the upper and lower respiratory tracts, including immunocompromised hosts chronically infected with the same strain over weeks or months. Phylogenetic analysis of 144 HRV-positive samples showed no apparent correlation between a given viral genotype or species and their ability to invade the lower respiratory tract or lead to protracted infection. By contrast, protracted infections were found almost exclusively in immunocompromised patients, thus suggesting that host factors rather than the virus genotype modulate disease outcome, in particular the immune response. Complete genome sequencing of five chronic cases to study rhinovirus genome adaptation showed that the calculated mutation frequency was in the range observed during acute human infections. Analysis of mutation hot spot regions between specimens collected at different times or in different body sites revealed that non-synonymous changes were mostly concentrated in the viral capsid genes VP1, VP2 and VP3, independent of the HRV type. In an immunosuppressed lung transplant recipient infected with the same HRV strain for more than two years, both classical and ultra-deep sequencing of samples collected at different time points in the upper and lower respiratory tracts showed that these virus populations were phylogenetically indistinguishable over the course of infection, except for the last month. Specific signatures were found in the last two lower respiratory tract populations, including changes in the 5′UTR polypyrimidine tract and the VP2 immunogenic site 2. These results highlight for the first time the ability of a given rhinovirus to evolve in the course of a natural infection in immunocompromised patients and complement data obtained from previous experimental inoculation studies in immunocompetent volunteers.",2011 Jun 21,"['Tapparel, Caroline', 'Cordey, Samuel', 'Junier, Thomas', 'Farinelli, Laurent', 'Van Belle, Sandra', 'Soccal, Paola M.', 'Aubert, John-David', 'Zdobnov, Evgeny', 'Kaiser, Laurent']",PLoS One,,,False
de793a20bfe9029e76531469de1054c4d5ef37c7,PMC,Immunogenicity and safety of virus-like particle of the porcine encephalomyocarditis virus in pig,http://dx.doi.org/10.1186/1743-422X-8-170,PMC3119933,21492483,CC BY,"BACKGROUND: In this study, porcine encephalomyocarditis virus (EMCV) virus-like particles (VLPs) were generated using a baculovirus expression system and were tested for immunogenicity and protective efficacy in vivo. RESULTS: VLPs were successfully generated from Sf9 cells infected with recombinant baculovirus and were confirmed to be approximately 30-40 nm by transmission electron microscopy (TEM). Immunization of mice with 0.5 μg crude protein containing the VLPs resulted in significant protection from EMCV infection (90%). In swine, increased neutralizing antibody titers were observed following twice immunization with 2.0 μg crude protein containing VLPs. In addition, high levels of neutralizing antibodies (from 64 to 512 fold) were maintained during a test period following the second immunization. No severe injection site reactions were observed after immunization and all swine were healthy during the immunization period CONCLUSION: Recombinant EMCV VLPs could represent a new vaccine candidate to protect against EMCV infection in pig farms.",2011 Apr 15,"['Jeoung, Hye-Young', 'Lee, Won-Ha', 'Jeong, WooSeog', 'Shin, Bo-Hye', 'Choi, Hwan-Won', 'Lee, Hee Soo', 'An, Dong-Jun']",Virol J,,,True
f6fa68c5038374d5ae1b2c1e5a0929e6c1e8ea44,PMC,Overexpression of human virus surface glycoprotein precursors induces cytosolic unfolded protein response in Saccharomyces cerevisiae,http://dx.doi.org/10.1186/1475-2859-10-37,PMC3120639,21595909,CC BY,"BACKGROUND: The expression of human virus surface proteins, as well as other mammalian glycoproteins, is much more efficient in cells of higher eukaryotes rather than yeasts. The limitations to high-level expression of active viral surface glycoproteins in yeast are not well understood. To identify possible bottlenecks we performed a detailed study on overexpression of recombinant mumps hemagglutinin-neuraminidase (MuHN) and measles hemagglutinin (MeH) in yeast Saccharomyces cerevisiae, combining the analysis of recombinant proteins with a proteomic approach. RESULTS: Overexpressed recombinant MuHN and MeH proteins were present in large aggregates, were inactive and totally insoluble under native conditions. Moreover, the majority of recombinant protein was found in immature form of non-glycosylated precursors. Fractionation of yeast lysates revealed that the core of viral surface protein aggregates consists of MuHN or MeH disulfide-linked multimers involving eukaryotic translation elongation factor 1A (eEF1A) and is closely associated with small heat shock proteins (sHsps) that can be removed only under denaturing conditions. Complexes of large Hsps seem to be bound to aggregate core peripherally as they can be easily removed at high salt concentrations. Proteomic analysis revealed that the accumulation of unglycosylated viral protein precursors results in specific cytosolic unfolded protein response (UPR-Cyto) in yeast cells, characterized by different action and regulation of small Hsps versus large chaperones of Hsp70, Hsp90 and Hsp110 families. In contrast to most environmental stresses, in the response to synthesis of recombinant MuHN and MeH, only the large Hsps were upregulated whereas sHsps were not. Interestingly, the amount of eEF1A was also increased during this stress response. CONCLUSIONS: Inefficient translocation of MuHN and MeH precursors through ER membrane is a bottleneck for high-level expression in yeast. Overexpression of these recombinant proteins induces the UPR's cytosolic counterpart, the UPR-Cyto, which represent a subset of proteins involved in the heat-shock response. The involvement of eEF1A may explain the mechanism by which only large chaperones, but not small Hsps are upregulated during this stress response. Our study highlights important differences between viral surface protein expression in yeast and mammalian cells at the first stage of secretory pathway.",2011 May 19,"['Čiplys, Evaldas', 'Samuel, Dhanraj', 'Juozapaitis, Mindaugas', 'Sasnauskas, Kęstutis', 'Slibinskas, Rimantas']",Microb Cell Fact,,,True
63cb88b9fee3f16bcf3666b4665e445325addf9d,PMC,Lytic HSV-1 infection induces the multifunctional transcription factor Early Growth Response-1 (EGR-1) in rabbit corneal cells,http://dx.doi.org/10.1186/1743-422X-8-262,PMC3120787,21619646,CC BY,"BACKGROUND: Herpes simplex virus type-1 (HSV-1) infections can cause a number of diseases ranging from simple cold sores to dangerous keratitis and lethal encephalitis. The interaction between virus and host cells, critical for viral replication, is being extensively investigated by many laboratories. In this study, we tested the hypothesis that HSV-1 lytic infection triggers the expression of important multi-functional transcription factor Egr1. The mechanisms of induction are mediated, at least in part, by signaling pathways such as NFκB and CREB. METHODS: SIRC, VERO, and 293HEK cell lines were infected with HSV-1, and the Egr-1 transcript and protein were detected by RT-PCR and Western blot, respectively. The localization and expression profile of Egr-1 were investigated further by immunofluorescence microscopy analyses. The recruitment of transcription factors to the Egr-1 promoter during infection was studied by chromatin immunoprecipitation (ChIP). Various inhibitors and dominant-negative mutant were used to assess the mechanisms of Egr-1 induction and their effects were addressed by immunofluorescence microscopy. RESULTS: Western blot analyses showed that Egr-1 was absent in uninfected cells; however, the protein was detected 24-72 hours post treatment, and the response was directly proportional to the titer of the virus used for infection. Using recombinant HSV-1 expressing EGFP, Egr-1 was detected only in the infected cells. ChIP assays demonstrated that NFкB and cAMP response element binding protein (CREB) were recruited to the Egr-1 promoter upon infection. Additional studies showed that inhibitors of NFкB and dominant-negative CREB repressed the Egr-1 induction by HSV-1 infection. CONCLUSION: Collectively, these results demonstrate that Egr-1 is expressed rapidly upon HSV-1 infection and that this novel induction could be due to the NFкB/CREB-mediated transactivation. Egr-1 induction might play a key role in the viral gene expression, replication, inflammation, and the disease progression.",2011 May 27,"['Bedadala, Gautam R', 'Palem, Jayavardhana R', 'Graham, Lorna', 'Hill, James M', 'McFerrin, Harris E', 'Hsia, Shao-Chung']",Virol J,,,True
052a16d442ede77ed4bdeaa05037270f251dedc4,PMC,A baculovirus dual expression system-based vaccine confers complete protection against lethal challenge with H9N2 avian influenza virus in mice,http://dx.doi.org/10.1186/1743-422X-8-273,PMC3120790,21639929,CC BY,"BACKGROUND: Avian influenza viruses of H9N2 subtype have become highly prevalent in avian species. Although these viruses generally cause only mild to moderate disease, they can infect a wide variety of species, including chickens, quail, turkeys, ducks, geese, pheasant, partridge, and pigeon, even transmitted to mammalian species, including humans, accelerating the efforts to devise protective strategies against them. RESULTS: The results showed that stronger immune responses were induced in a mouse model immunized with BV-Dual-HA than in those vaccinated with a DNA vaccine encoding the same antigen. Moreover, complete protection against lethal challenge with H9N2 virus was observed in mice. CONCLUSION: BV-Dual-HA could be utilized as a vaccine candidate against H9N2 virus infection.",2011 Jun 4,"['Lin, Wenyao', 'Fan, Huiying', 'Cheng, Xiaoliang', 'Ye, Yu', 'Chen, Xiaowei', 'Ren, Tao', 'Qi, Wenbao', 'Liao, Ming']",Virol J,,,True
db7db8941a68a14e0b227ce42898ad4ecd40df62,PMC,Public Health Emergency Preparedness and Response Communications with Health Care Providers: A Literature Review,http://dx.doi.org/10.1186/1471-2458-11-337,PMC3121631,21592390,CC BY,"BACKGROUND: Health care providers (HCPs) play an important role in public health emergency preparedness and response (PHEPR) so need to be aware of public health threats and emergencies. To inform HCPs, public health issues PHEPR messages that provide guidelines and updates, and facilitate surveillance so HCPs will recognize and control communicable diseases, prevent excess deaths and mitigate suffering. Public health agencies need to know that the PHEPR messages sent to HCPs reach their target audience and are effective and informative. Public health agencies need to know that the PHEPR messages sent to HCPs reach their target audience and are effective and informative. We conducted a literature review to investigate the systems and tools used by public health to generate PHEPR communications to HCPs, and to identify specific characteristics of message delivery mechanisms and formats that may be associated with effective PHEPR communications. METHODS: A systematic review of peer- and non-peer-reviewed literature focused on the following questions: 1) What public health systems exist for communicating PHEPR messages from public health agencies to HCPs? 2) Have these systems been evaluated and, if yes, what criteria were used to evaluate these systems? 3) What have these evaluations discovered about characterizations of the most effective ways for public health agencies to communicate PHEPR messages to HCPs? RESULTS: We identified 25 systems or tools for communicating PHEPR messages from public health agencies to HCPs. Few articles assessed PHEPR communication systems or messaging methods or outcomes. Only one study compared the effectiveness of the delivery format, device or message itself. We also discovered that the potential is high for HCPs to experience ""message overload"" given redundancy of PHEPR messaging in multiple formats and/or through different delivery systems. CONCLUSIONS: We found that detailed descriptions of PHEPR messaging from public health to HCPs are scarce in the literature and, even when available are rarely evaluated in any systematic fashion. To meet present-day and future information needs for emergency preparedness, more attention needs to be given to evaluating the effectiveness of these systems in a scientifically rigorous manner.",2011 May 18,"['Revere, Debra', 'Nelson, Kailey', 'Thiede, Hanne', 'Duchin, Jeffrey', 'Stergachis, Andy', 'Baseman, Janet']",BMC Public Health,,,True
816359485f5bb752e2024fae9fe790cc1ff80f81,PMC,StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase,http://dx.doi.org/10.1186/1471-2105-12-226,PMC3121648,21635786,CC BY,"BACKGROUND: Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory--still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could help overcome these difficulties by facilitating the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. RESULTS: Here we present StralSV (structure-alignment sequence variability), a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus, and we demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique, or that share structural similarity with proteins that would be considered distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local structural alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. CONCLUSIONS: StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected residues at a given sequence position. StralSV is provided as a web service at http://proteinmodel.org/AS2TS/STRALSV/.",2011 Jun 2,"['Zemla, Adam T', 'Lang, Dorothy M', 'Kostova, Tanya', 'Andino, Raul', 'Ecale Zhou, Carol L']",BMC Bioinformatics,,,True
5ffaf1c1d5f763636ec3334c1b1547d4a8b8abb9,PMC,Human bocavirus (HBoV) in children with respiratory tract infection by enzyme linked immunosorbent assay (ELISA) and qualitative polymerase chain reaction (PCR),http://dx.doi.org/10.1186/1743-422X-8-239,PMC3121704,21595869,CC BY,"BACKGROUND: Human bocavirus (HBoV) is a recently discovered parvovirus associated with mild to severe lower respiratory tract infections in children, the aim of the work was determination of human bocavirus in nasopharyngeal aspirate (NPA) of infants by qualitative PCR and determination of acute human bocavirus infection by estimation of immunoglobulin M (IgM) antibodies in serum by enzyme linked immunosorbent assay. RESULTS: Twenty two (22%) out of the 100 NPA specimens of the patients with respiratory manifestations were positive for HBoV by qualitative PCR, while ELISA revealed positive HBoV IgM antibodies in 18 (18%) patients who were also positive by PCR. Non of the controls were positive by both techniques. The correlation study between ELISA and PCR revealed high significant association, (p < 0.001, X(2 )= 36 and agreement = 96%). Also PCR detected 4 (18.1%) NPA samples as HBoV positive cases among the patients that were not identified by ELISA. This could be due to high sensitivity and efficacy of PCR. ELISA being less sensitive than RT-PCR, sensitivity was (81.8% vs 100%), the efficacy was 97.7% in ELISA versus 99.7% for RT-PCR. CONCLUSION: HBoV infections could be diagnosed in NPA of children by conventional PCR as a rapid and sensitive technique. While ELISA was a reliable serologic analysis for diagnosis of acute HBoV infection by estimation IgM antibodies in serum.",2011 May 19,"Zaghloul, Mona Z",Virol J,,,True
a2c46da8970ae5d4e6b3b1f4d4d30a2ea426d1ff,PMC,Self-Collected Mid-Turbinate Swabs for the Detection of Respiratory Viruses in Adults with Acute Respiratory Illnesses,http://dx.doi.org/10.1371/journal.pone.0021335,PMC3121745,21731708,CC BY,"BACKGROUND: The gold standard for respiratory virus testing is a nasopharyngeal (NP) swab, which is collected by a healthcare worker. Midturbinate (MT) swabs are an alternative due to their ease of collection and possible self-collection by patients. The objective of this study was to compare the respiratory virus isolation of flocked MT swabs compared to flocked NP swabs. METHODS: Beginning in October 2008, healthy adults aged 18 to 69 years were recruited into a cohort and followed up for symptoms of influenza. They were asked to have NP and MT swabs taken as soon as possible after the onset of a fever or two or more respiratory symptoms with an acute onset. The swabs were tested for viral respiratory infections using Seeplex® RV12 multiplex PCR detection kit. Seventy six pairs of simultaneous NP and MT swabs were collected from 38 symptomatic subjects. Twenty nine (38%) of these pairs were positive by either NP or MT swabs or both. Sixty nine (91%) of the pair results were concordant. Two samples (3%) for hCV OC43/HKU1 and 1 sample (1%) for rhinovirus A/B were positive by NP but negative by MT. One sample each for hCV 229E/NL63, hCV OC43/HKU1, respiratory syncytial virus A, and influenza B were positive by MT but negative by NP. CONCLUSIONS: Flocked MT swabs are sensitive for the diagnosis of multiple respiratory viruses. Given the ease of MT collection and similar results between the two swabs, it is likely that MT swabs should be the preferred method of respiratory cell collection for outpatient studies. In light of this data, larger studies should be performed to ensure that this still holds true and data should also be collected on the patient preference of collection methods.",2011 Jun 23,"['Larios, Oscar E.', 'Coleman, Brenda L.', 'Drews, Steven J.', 'Mazzulli, Tony', 'Borgundvaag, Bjug', 'Green, Karen', None, 'McGeer, Allison J.']",PLoS One,,,True
d94872b6508c7d1b3bf580ff888aa862047ded07,PMC,Rabies-Related Knowledge and Practices Among Persons At Risk of Bat Exposures in Thailand,http://dx.doi.org/10.1371/journal.pntd.0001054,PMC3125144,21738801,CC0,"BACKGROUND: Rabies is a fatal encephalitis caused by lyssaviruses. Evidence of lyssavirus circulation has recently emerged in Southeast Asian bats. A cross-sectional study was conducted in Thailand to assess rabies-related knowledge and practices among persons regularly exposed to bats and bat habitats. The objectives were to identify deficiencies in rabies awareness, describe the occurrence of bat exposures, and explore factors associated with transdermal bat exposures. METHODS: A survey was administered to a convenience sample of adult guano miners, bat hunters, game wardens, and residents/personnel at Buddhist temples where mass bat roosting occurs. The questionnaire elicited information on demographics, experience with bat exposures, and rabies knowledge. Participants were also asked to describe actions they would take in response to a bat bite as well as actions for a bite from a potentially rabid animal. Bivariate analysis was used to compare responses between groups and multivariable logistic regression was used to explore factors independently associated with being bitten or scratched by a bat. FINDINGS: Of 106 people interviewed, 11 (10%) identified bats as a potential source of rabies. A history of a bat bite or scratch was reported by 29 (27%), and 38 (36%) stated either that they would do nothing or that they did not know what they would do in response to a bat bite. Guano miners were less likely than other groups to indicate animal bites as a mechanism of rabies transmission (68% vs. 90%, p = 0.03) and were less likely to say they would respond appropriately to a bat bite or scratch (61% vs. 27%, p = 0.003). Guano mining, bat hunting, and being in a bat cave or roost area more than 5 times a year were associated with history of a bat bite or scratch. CONCLUSIONS: These findings indicate the need for educational outreach to raise awareness of bat rabies, promote exposure prevention, and ensure appropriate health-seeking behaviors for bat-inflicted wounds, particularly among at-risk groups in Thailand.",2011 Jun 28,"['Robertson, Kis', 'Lumlertdacha, Boonlert', 'Franka, Richard', 'Petersen, Brett', 'Bhengsri, Saithip', 'Henchaichon, Sununta', 'Peruski, Leonard F.', 'Baggett, Henry C.', 'Maloney, Susan A.', 'Rupprecht, Charles E.']",PLoS Negl Trop Dis,,,True
16f4fcc0f008c01ee4711085e070b3dcb17040d4,PMC,"Host range, host specificity and hypothesized host shift events among viruses of lower vertebrates",http://dx.doi.org/10.1186/1297-9716-42-67,PMC3125225,21592358,CC BY,"The successful replication of a viral agent in a host is a complex process that often leads to a species specificity of the virus and can make interspecies transmission difficult. Despite this difficulty, natural host switch seems to have been frequent among viruses of lower vertebrates, especially fish viruses, since there are several viruses known to be able to infect a wide range of species. In the present review we will focus on well documented reports of broad host range, variations in host specificity, and host shift events hypothesized for viruses within the genera Ranavirus, Novirhabdovirus, Betanodavirus, Isavirus, and some herpesvirus.",2011 May 18,"['Bandín, Isabel', 'Dopazo, Carlos P']",Vet Res,,,True
d6cbaee69496b4617b6032c4b82cfc7afe601fac,PMC,Antibodies on demand: a fast method for the production of human scFvs with minimal amounts of antigen,http://dx.doi.org/10.1186/1472-6750-11-61,PMC3125328,21635725,CC BY,"BACKGROUND: Antibodies constitute a powerful tool to study protein function, protein localization and protein-protein interactions, as well as for diagnostic and therapeutic purposes. High-throughput antibody development requires faster methodologies with lower antigen consumption. RESULTS: Here, we describe a novel methodology to select human monoclonal recombinant antibodies by combining in vitro protein expression, phage display antibody libraries and antibody microarrays. The application of this combination of methodologies permitted us to generate human single-chain variable fragments (scFvs) against two proteins: green fluorescent protein (GFP) and thioredoxin (Trx) in a short time, using as low as 5 μg of purified protein. These scFvs showed specific reactivity against their respective targets and worked well by ELISA and western blot. The scFvs were able to recognise as low as 31 ng of protein of their respective targets by western blot. CONCLUSION: This work describes a novel and miniaturized methodology to obtain human monoclonal recombinant antibodies against any target in a shorter time than other methodologies using only 5 μg of protein. The protocol could be easily adapted to a high-throughput procedure for antibody production.",2011 Jun 2,"['Babel, Ingrid', 'Barderas, Rodrigo', 'Peláez-García, Alberto', 'Casal, J Ignacio']",BMC Biotechnol,,,True
fd521d37325a60e6ed92aa9bcf4541b9a68ee90e,PMC,Identification of CD8(+ )cytotoxic T lymphocyte epitopes from porcine reproductive and respiratory syndrome virus matrix protein in BALB/c mice,http://dx.doi.org/10.1186/1743-422X-8-263,PMC3126774,21619712,CC BY,"Twenty-seven nanopeptides derived from the matrix (M) protein of porcine reproductive and respiratory syndrome virus (PRRSV) were screened for their ability to elicit a recall interferon-γ (IFN-γ) response from the splenocytes of BALB/c mice following DNA vaccination and a booster vaccination with recombinant vaccinia virus rWR-PRRSV-M. We identified two peptides (amino acid residues K(93)FITSRCRL and F(57)GYMTFVHF) as CD8(+ )cytotoxic T lymphocyte (CTL) epitopes. These peptides elicited significant numbers of IFN-γ secreting cells, compared with other M nonapeptides and one irrelevant nonapeptide. Bioinformatics analysis showed that the former is an H-2K(d)-restricted CTL epitope, and the latter is an H-2D(d)-restricted CTL epitope. Multiple amino acid sequence alignment among different PRRSV M sequences submitted to GenBank indicated that these two CTL epitopes are strongly conserved, and they should therefore be considered for further research on the mechanisms of cellular immune responses to PRRSV.",2011 May 30,"['Zhang, Weijun', 'Lin, Yan', 'Bai, Yu', 'Tong, Tiegang', 'Wang, Qun', 'Liu, Nihong', 'Liu, Guangliang', 'Xiao, Yihong', 'Yang, Tao', 'Bu, Zhigao', 'Tong, Guangzhi', 'Wu, Donglai']",Virol J,,,True
fa2c978f246035c7e524e301c1ed8f9a5178dfde,PMC,Computer-based fluorescence quantification: a novel approach to study nucleolar biology,http://dx.doi.org/10.1186/1471-2121-12-25,PMC3126779,21639891,CC BY,"BACKGROUND: Nucleoli are composed of possibly several thousand different proteins and represent the most conspicuous compartments in the nucleus; they play a crucial role in the proper execution of many cellular processes. As such, nucleoli carry out ribosome biogenesis and sequester or associate with key molecules that regulate cell cycle progression, tumorigenesis, apoptosis and the stress response. Nucleoli are dynamic compartments that are characterized by a constant flux of macromolecules. Given the complex and dynamic composition of the nucleolar proteome, it is challenging to link modifications in nucleolar composition to downstream effects. RESULTS: In this contribution, we present quantitative immunofluorescence methods that rely on computer-based image analysis. We demonstrate the effectiveness of these techniques by monitoring the dynamic association of proteins and RNA with nucleoli under different physiological conditions. Thus, the protocols described by us were employed to study stress-dependent changes in the nucleolar concentration of endogenous and GFP-tagged proteins. Furthermore, our methods were applied to measure de novo RNA synthesis that is associated with nucleoli. We show that the techniques described here can be easily combined with automated high throughput screening (HTS) platforms, making it possible to obtain large data sets and analyze many of the biological processes that are located in nucleoli. CONCLUSIONS: Our protocols set the stage to analyze in a quantitative fashion the kinetics of shuttling nucleolar proteins, both at the single cell level as well as for a large number of cells. Moreover, the procedures described here are compatible with high throughput image acquisition and analysis using HTS automated platforms, thereby providing the basis to quantify nucleolar components and activities for numerous samples and experimental conditions. Together with the growing amount of information obtained for the nucleolar proteome, improvements in quantitative microscopy as they are described here can be expected to produce new insights into the complex biological functions that are orchestrated by the nucleolus.",2011 Jun 3,"['Kodiha, Mohamed', 'Bański, Piotr', 'Stochaj, Ursula']",BMC Cell Biol,,,True
79a70e09a449e41078a23b502c9a645a1e177eca,PMC,Is Network Clustering Detectable in Transmission Trees?,http://dx.doi.org/10.3390/v3060659,PMC3127449,21731813,CC BY,"Networks are often used to model the contact processes that allow pathogens to spread between hosts but it remains unclear which models best describe these networks. One question is whether clustering in networks, roughly defined as the propensity for triangles to form, affects the dynamics of disease spread. We perform a simulation study to see if there is a signal in epidemic transmission trees of clustering. We simulate susceptible-exposed-infectious-removed (SEIR) epidemics (with no re-infection) over networks with fixed degree sequences but different levels of clustering and compare trees from networks with the same degree sequence and different clustering levels. We find that the variation of such trees simulated on networks with different levels of clustering is barely greater than those simulated on networks with the same level of clustering, suggesting that clustering can not be detected in transmission data when re-infection does not occur.",2011 Jun 3,"Welch, David",Viruses,,,True
3f06c41154ff140670ba10f54eeaf640c39f29b9,PMC,Network Clustering Revealed the Systemic Alterations of Mitochondrial Protein Expression,http://dx.doi.org/10.1371/journal.pcbi.1002093,PMC3127811,21738461,CC BY,"The mitochondrial protein repertoire varies depending on the cellular state. Protein component modifications caused by mitochondrial DNA (mtDNA) depletion are related to a wide range of human diseases; however, little is known about how nuclear-encoded mitochondrial proteins (mt proteome) changes under such dysfunctional states. In this study, we investigated the systemic alterations of mtDNA-depleted (ρ(0)) mitochondria by using network analysis of gene expression data. By modularizing the quantified proteomics data into protein functional networks, systemic properties of mitochondrial dysfunction were analyzed. We discovered that up-regulated and down-regulated proteins were organized into two predominant subnetworks that exhibited distinct biological processes. The down-regulated network modules are involved in typical mitochondrial functions, while up-regulated proteins are responsible for mtDNA repair and regulation of mt protein expression and transport. Furthermore, comparisons of proteome and transcriptome data revealed that ρ(0) cells attempted to compensate for mtDNA depletion by modulating the coordinated expression/transport of mt proteins. Our results demonstrate that mt protein composition changed to remodel the functional organization of mitochondrial protein networks in response to dysfunctional cellular states. Human mt protein functional networks provide a framework for understanding how cells respond to mitochondrial dysfunctions.",2011 Jun 30,"['Jeon, Jouhyun', 'Jeong, Jae Hoon', 'Baek, Je-Hyun', 'Koo, Hyun-Jung', 'Park, Wook-Ha', 'Yang, Jae-Seong', 'Yu, Myeong-Hee', 'Kim, Sanguk', 'Pak, Youngmi Kim']",PLoS Comput Biol,,,True
b514652703a631715ca85e65499c66016fb994d4,PMC,Snowbirds and infection--new phenomena in pneumonia and influenza hospitalizations from winter migration of older adults: A spatiotemporal analysis,http://dx.doi.org/10.1186/1471-2458-11-444,PMC3128025,21649919,CC BY,"BACKGROUND: Despite advances in surveillance and prevention, pneumonia and influenza (P&I) remain among the leading causes of mortality in the United States. Elderly adults experience the most severe morbidity from influenza-associated diseases, and have the highest rates of seasonal migration within the U.S. compared to other subpopulations. The objective of this study is to assess spatiotemporal patterns in influenza-associated hospitalizations in the elderly, by time, geography, and intensity of P&I. Given the high seasonal migration of individuals to Florida, this state was examined more closely using harmonic regression to assess spatial and temporal patterns of P&I hospitalizations by state of residence. METHODS: Data containing all Medicare-eligible hospitalizations in the United States for 1991-2006 with P&I (ICD-9-CM codes 480-487) were abstracted for the 65+ population. Hospitalizations were classified by state of residence, provider state, and date of admissions, specifically comparing those admitted between October and March to those admitted between April and September. We then compared the hospitalization profile data of Florida residents with that of out-of-state residents by state of primary residence and time of year (in-season or out-of-season). RESULTS: We observed distinct seasonal patterns of nonresident P&I hospitalizations, especially comparing typical winter destination states, such as California, Arizona, Texas, and Florida, to other states. Although most other states generally experienced a higher proportion of non-resident P&I during the summer months (April-September), these states had higher nonresident P&I during the traditional peak influenza season (October-March). CONCLUSIONS: This study is among the first to quantify spatiotemporal P&I hospitalization patterns in the elderly, focusing on the change of patterns that are possibly due to seasonal population migration. Understanding migration and influenza-associated disease patterns in this vulnerable population is critical to prepare for and potentially prevent influenza outbreaks in this vulnerable population.",2011 Jun 7,"['Chui, Kenneth KH', 'Cohen, Steven A', 'Naumova, Elena N']",BMC Public Health,,,True
7025d7269f1bc09bfb96f51de30e2e0309a3fadc,PMC,Viral-bacterial co-infection in Australian Indigenous children with acute otitis media,http://dx.doi.org/10.1186/1471-2334-11-161,PMC3128050,21649905,CC BY,"BACKGROUND: Acute otitis media with perforation (AOMwiP) affects 40% of remote Indigenous children during the first 18 months of life. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the primary bacterial pathogens of otitis media and their loads predict clinical ear state. Our hypothesis is that antecedent respiratory viral infection increases bacterial density and progression to perforation. METHODS: A total of 366 nasopharyngeal swabs from 114 Indigenous children were retrospectively examined. A panel of 17 respiratory viruses was screened by PCR, and densities of S. pneumoniae, H. influenzae and M. catarrhalis were estimated by quantitative real time PCR. Data are reported by clinical ear state. RESULTS: M. catarrhalis (96%), H. influenzae (91%), S. pneumoniae (89%) and respiratory viruses (59%) were common; including rhinovirus (HRV) (38%), polyomavirus (HPyV) (14%), adenovirus (HAdV) (13%), bocavirus (HBoV) (8%) and coronavirus (HCoV) (4%). Geometric mean bacterial loads were significantly higher in children with acute otitis media (AOM) compared to children without evidence of otitis media. Children infected with HAdV were 3 times more likely (p < 0.001) to have AOM with or without perforation. CONCLUSION: This study confirms a positive association between nasopharyngeal bacterial load and clinical ear state, exacerbated by respiratory viruses, in Indigenous children. HAdV was independently associated with acute ear states.",2011 Jun 7,"['Binks, Michael J', 'Cheng, Allen C', 'Smith-Vaughan, Heidi', 'Sloots, Theo', 'Nissen, Michael', 'Whiley, David', 'McDonnell, Joseph', 'Leach, Amanda J']",BMC Infect Dis,,,True
95cff929be1b2765e78d6293e4722f404a814011,PMC,How to make predictions about future infectious disease risks,http://dx.doi.org/10.1098/rstb.2010.0387,PMC3130384,21624924,CC BY,"Formal, quantitative approaches are now widely used to make predictions about the likelihood of an infectious disease outbreak, how the disease will spread, and how to control it. Several well-established methodologies are available, including risk factor analysis, risk modelling and dynamic modelling. Even so, predictive modelling is very much the ‘art of the possible’, which tends to drive research effort towards some areas and away from others which may be at least as important. Building on the undoubted success of quantitative modelling of the epidemiology and control of human and animal diseases such as AIDS, influenza, foot-and-mouth disease and BSE, attention needs to be paid to developing a more holistic framework that captures the role of the underlying drivers of disease risks, from demography and behaviour to land use and climate change. At the same time, there is still considerable room for improvement in how quantitative analyses and their outputs are communicated to policy makers and other stakeholders. A starting point would be generally accepted guidelines for ‘good practice’ for the development and the use of predictive models.",2011 Jul 12,"Woolhouse, Mark",Philos Trans R Soc Lond B Biol Sci,,,True
7dc484e62b5a5e470b072184f55b023d5e751061,PMC,Ceacam1 Separates Graft-versus-Host-Disease from Graft-versus-Tumor Activity after Experimental Allogeneic Bone Marrow Transplantation,http://dx.doi.org/10.1371/journal.pone.0021611,PMC3130781,21760897,CC BY,"BACKGROUND: Allogeneic bone marrow transplantation (allo-BMT) is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT) activity are limited by graft-versus-host-disease (GVHD). Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1) is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models. METHODS: We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT) in mouse models. In vivo, Ceacam1(−/−) T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi), CD62L(lo)). Additionally, Ceacam1(−/−) CD8 T cells had greater expression of the gut-trafficking integrin α(4)β(7), though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(−/−) recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(−/−) mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+) lymphoma model was improved in animals receiving Ceacam1(−/−) vs. control T cells. CONCLUSIONS: We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the donor graft and host tissues, this suggests that targeting Ceacam1 may represent a potent strategy for the regulation of GVHD and GVT after allogeneic transplantation.",2011 Jul 6,"['Lu, Sydney X.', 'Kappel, Lucy W.', 'Charbonneau-Allard, Anne-Marie', 'Atallah, Renée', 'Holland, Amanda M.', 'Turbide, Claire', 'Hubbard, Vanessa M.', 'Rotolo, Jimmy A.', 'Smith, Marsinay', 'Suh, David', 'King, Christopher', 'Rao, Uttam K.', 'Yim, Nury', 'Bautista, Johanne L.', 'Jenq, Robert R.', 'Penack, Olaf', 'Na, Il-Kang', 'Liu, Chen', 'Murphy, George', 'Alpdogan, Onder', 'Blumberg, Richard S.', 'Macian, Fernando', 'Holmes, Kathryn V.', 'Beauchemin, Nicole', 'van den Brink, Marcel R. M.']",PLoS One,,,True
06c0371d82953f5c35ee8bff3e5165d5aa1516de,PMC,Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection,http://dx.doi.org/10.1371/journal.ppat.1001347,PMC3131267,21750671,CC BY,"The inhibitory receptor programmed death-1 (PD-1) has the capacity to maintain peripheral tolerance and limit immunopathological damage; however, its precise role in fulminant viral hepatitis (FH) has yet to be described. Here, we investigated the functional mechanisms of PD-1 as related to FH pathogenesis induced by the murine hepatitis virus strain-3 (MHV-3). High levels of PD-1-positive CD4(+), CD8(+) T cells, NK cells and macrophages were observed in liver, spleen, lymph node and thymus tissues following MHV-3 infection. PD-1-deficient mice exhibited significantly higher expression of the effector molecule which initiates fibrinogen deposition, fibrinogen-like protein 2 (FGL2), than did their wild-type (WT) littermates. As a result, more severe tissue damage was produced and mortality rates were higher. Fluorescence double-staining revealed that FGL2 and PD-1 were not co-expressed on the same cells, while quantitative RT-PCR demonstrated that higher levels of IFN-γ and TNF-α mRNA transcription occurred in PD-1-deficient mice in response to MHV-3 infection. Conversely, in vivo blockade of IFN-γ and TNF-α led to efficient inhibition of FGL2 expression, greatly attenuated the development of tissue lesions, and ultimately reduced mortality. Thus, the up-regulation of FGL2 in PD-1-deficient mice was determined to be mediated by IFN-γ and TNF-α. Taken together, our results suggest that PD-1 signaling plays an essential role in decreasing the immunopathological damage induced by MHV-3 and that manipulation of this signal might be a useful strategy for FH immunotherapy.",2011 Jul 7,"['Chen, Yongwen', 'Wu, Shengxi', 'Guo, Guoning', 'Fei, Lei', 'Guo, Sheng', 'Yang, Chengying', 'Fu, Xiaolan', 'Wu, Yuzhang']",PLoS Pathog,,,True
0c22edd80a03a1b9de7f3d29b729ad1006d10674,PMC,Machupo Virus Glycoprotein Determinants for Human Transferrin Receptor 1 Binding and Cell Entry,http://dx.doi.org/10.1371/journal.pone.0021398,PMC3131282,21750710,CC0,"Machupo virus (MACV) is a highly pathogenic New World arenavirus that causes hemorrhagic fever in humans. MACV, as well as other pathogenic New World arenaviruses, enter cells after their GP1 attachment glycoprotein binds to their cellular receptor, transferrin receptor 1 (TfR1). TfR1 residues essential for this interaction have been described, and a co-crystal of MACV GP1 bound to TfR1 suggests GP1 residues important for this association. We created MACV GP1 variants and tested their effect on TfR1 binding and virus entry to evaluate the functional significance of some of these and additional residues in human and simian cells. We found residues R111, D123, Y122, and F226 to be essential, D155, and P160 important, and D114, S116, D140, and K169 expendable for the GP1-TfR1 interaction and MACV entry. Several MACV GP1 residues that are critical for the interaction with TfR1 are conserved among other New World arenaviruses, indicating a common basis of receptor interaction. Our findings also open avenues for the rational development of viral entry inhibitors.",2011 Jul 7,"['Radoshitzky, Sheli R.', 'Longobardi, Lindsay E.', 'Kuhn, Jens H.', 'Retterer, Cary', 'Dong, Lian', 'Clester, Jeremiah C.', 'Kota, Krishna', 'Carra, John', 'Bavari, Sina']",PLoS One,,,True
7212e4cdbb493aa171b9d07c3946114d715f1e5b,PMC,GI-type T4SS-mediated horizontal transfer of the 89K pathogenicity island in epidemic Streptococcus suis serotype 2,http://dx.doi.org/10.1111/j.1365-2958.2011.07553.x,PMC3132442,21244532,CC BY,"Pathogenicity islands (PAIs), a distinct type of genomic island (GI), play important roles in the rapid adaptation and increased virulence of pathogens. 89K is a newly identified PAI in epidemic Streptococcus suis isolates that are related to the two recent large-scale outbreaks of human infection in China. However, its mechanism of evolution and contribution to the epidemic spread of S. suis 2 remain unknown. In this study, the potential for mobilization of 89K was evaluated, and its putative transfer mechanism was investigated. We report that 89K can spontaneously excise to form an extrachromosomal circular product. The precise excision is mediated by an 89K-borne integrase through site-specific recombination, with help from an excisionase. The 89K excision intermediate acts as a substrate for lateral transfer to non-89K S. suis 2 recipients, where it reintegrates site-specifically into the target site. The conjugal transfer of 89K occurred via a GI type IV secretion system (T4SS) encoded in 89K, at a frequency of 10(−6) transconjugants per donor. This is the first demonstration of horizontal transfer of a Gram-positive PAI mediated by a GI-type T4SS. We propose that these genetic events are important in the emergence, pathogenesis and persistence of epidemic S. suis 2 strains.",2011 Mar,"['Li, Ming', 'Shen, Xiaodong', 'Yan, Jinghua', 'Han, Huiming', 'Zheng, Beiwen', 'Liu, Di', 'Cheng, Hao', 'Zhao, Yan', 'Rao, Xiancai', 'Wang, Changjun', 'Tang, Jiaqi', 'Hu, Fuquan', 'Gao, George F']",Mol Microbiol,,,True
6cdc67641b41343d179febae3d95e5ce6fabcb21,PMC,GI-type T4SS-mediated horizontal transfer of the 89K pathogenicity island in epidemic Streptococcus suis serotype 2,http://dx.doi.org/10.1111/j.1365-2958.2011.07553.x,PMC3132442,21244532,CC BY,"Pathogenicity islands (PAIs), a distinct type of genomic island (GI), play important roles in the rapid adaptation and increased virulence of pathogens. 89K is a newly identified PAI in epidemic Streptococcus suis isolates that are related to the two recent large-scale outbreaks of human infection in China. However, its mechanism of evolution and contribution to the epidemic spread of S. suis 2 remain unknown. In this study, the potential for mobilization of 89K was evaluated, and its putative transfer mechanism was investigated. We report that 89K can spontaneously excise to form an extrachromosomal circular product. The precise excision is mediated by an 89K-borne integrase through site-specific recombination, with help from an excisionase. The 89K excision intermediate acts as a substrate for lateral transfer to non-89K S. suis 2 recipients, where it reintegrates site-specifically into the target site. The conjugal transfer of 89K occurred via a GI type IV secretion system (T4SS) encoded in 89K, at a frequency of 10(−6) transconjugants per donor. This is the first demonstration of horizontal transfer of a Gram-positive PAI mediated by a GI-type T4SS. We propose that these genetic events are important in the emergence, pathogenesis and persistence of epidemic S. suis 2 strains.",2011 Mar,"['Li, Ming', 'Shen, Xiaodong', 'Yan, Jinghua', 'Han, Huiming', 'Zheng, Beiwen', 'Liu, Di', 'Cheng, Hao', 'Zhao, Yan', 'Rao, Xiancai', 'Wang, Changjun', 'Tang, Jiaqi', 'Hu, Fuquan', 'Gao, George F']",Mol Microbiol,,,False
b470eec84fd5bb0a9a7079506df05c3cdf398832,PMC,Cross-Reactive Human IgM-Derived Monoclonal Antibodies that Bind to HIV-1 Envelope Glycoproteins,http://dx.doi.org/10.3390/v2020547,PMC3133461,21755021,CC BY,"Elicitation of antibodies with potent and broad neutralizing activity against HIV by immunization remains a challenge. Several monoclonal antibodies (mAbs) isolated from humans with HIV-1 infection exhibit such activity but vaccine immunogens based on structures containing their epitopes have not been successful for their elicitation. All known broadly neutralizing mAbs (bnmAbs) are immunoglobulin (Ig) Gs (IgGs) and highly somatically hypermutated which could impede their elicitation. Ig Ms (IgMs) are on average significantly less divergent from germline antibodies and are relevant for the development of vaccine immunogens but are underexplored compared to IgGs. Here we describe the identification and characterization of several human IgM-derived mAbs against HIV-1 which were selected from a large phage-displayed naive human antibody library constructed from blood, lymph nodes and spleens of 59 healthy donors. These antibodies bound with high affinity to recombinant envelope glycoproteins (gp140s, Envs) of HIV-1 isolates from different clades. They enhanced or did not neutralize infection by some of the HIV-1 primary isolates using CCR5 as a coreceptor but neutralized all CXCR4 isolates tested although weakly. One of these antibodies with relatively low degree of somatic hypermutation was more extensively characterized. It bound to a highly conserved region partially overlapping with the coreceptor binding site and close to but not overlapping with the CD4 binding site. These results suggest the existence of conserved structures that could direct the immune response to non-neutralizing or even enhancing antibodies which may represent a strategy used by the virus to escape neutralizing immune responses. Further studies will show whether such a strategy plays a role in HIV infection of humans, how important that role could be, and what the mechanisms of infection enhancement are. The newly identified mAbs could be used as reagents to further characterize conserved non-neutralizing, weakly neutralizing or enhancing epitopes and modify or remove them from candidate vaccine immunogens.",2010 Feb 4,"['Chen, Weizao', 'Zhu, Zhongyu', 'Liao, Huaxin', 'Quinnan, Gerald V.', 'Broder, Christopher C.', 'Haynes, Barton F.', 'Dimitrov, Dimiter S.']",Viruses,,,True
6fe5d96d6e7a93c94a8788af735bdc919cd8d71d,PMC,A Conformation-Sensitive Monoclonal Antibody against the A2 Domain of von Willebrand Factor Reduces Its Proteolysis by ADAMTS13,http://dx.doi.org/10.1371/journal.pone.0022157,PMC3133621,21779388,CC BY,"The size of von Willebrand factor (VWF), controlled by ADAMTS13-dependent proteolysis, is associated with its hemostatic activity. Many factors regulate ADAMTS13-dependent VWF proteolysis through their interaction with VWF. These include coagulation factor VIII, platelet glycoprotein 1bα, and heparin sulfate, which accelerate the cleavage of VWF. Conversely, thrombospondin-1 decreases the rate of VWF proteolysis by ADAMTS13 by competing with ADAMTS13 for the A3 domain of VWF. To investigate whether murine monoclonal antibodies (mAbs) against human VWF affect the susceptibility of VWF to proteolysis by ADAMTS13 in vitro, eight mAbs to different domains of human VWF were used to evaluate the effects on VWF cleavage by ADAMTS13 under fluid shear stress and static/denaturing conditions. Additionally, the epitope of anti-VWF mAb (SZ34) was mapped using recombinant proteins in combination with enzyme-linked immunosorbent assay and Western blot analysis. The results indicate that mAb SZ34 inhibited proteolytic cleavage of VWF by ADAMTS13 in a concentration-dependent manner under fluid shear stress, but not under static/denaturing conditions. The binding epitope of SZ34 mAb is located between A1555 and G1595 in the central A2 domain of VWF. These data show that an anti-VWF mAb against the VWF-A2 domain (A1555-G1595) reduces the proteolytic cleavage of VWF by ADAMTS13 under shear stress, suggesting the role of this region in interaction with ADAMTS13.",2011 Jul 11,"['Zhang, Jingyu', 'Ma, Zhenni', 'Dong, Ningzheng', 'Liu, Fang', 'Su, Jian', 'Zhao, Yiming', 'Shen, Fei', 'Wang, Anyou', 'Ruan, Changgeng']",PLoS One,,,True
f7185938312bfa794681998fe0bff4e2697c053d,PMC,An Overview on the Field of Micro- and Nanotechnologies for Synthetic Peptide-Based Vaccines,http://dx.doi.org/10.1155/2011/181646,PMC3134826,21773041,CC BY,"The development of synthetic peptide-based vaccines has many advantages in comparison with vaccines based on live attenuated organisms, inactivated or killed organism, or toxins. Peptide-based vaccines cannot revert to a virulent form, allow a better conservation, and are produced more easily and safely. However, they generate a weaker immune response than other vaccines, and the inclusion of adjuvants and/or the use of vaccine delivery systems is almost always needed. Among vaccine delivery systems, micro- and nanoparticulated ones are attractive, because their particulate nature can increase cross-presentation of the peptide. In addition, they can be passively or actively targeted to antigen presenting cells. Furthermore, particulate adjuvants are able to directly activate innate immune system in vivo. Here, we summarize micro- and nanoparticulated vaccine delivery systems used in the field of synthetic peptide-based vaccines as well as strategies to increase their immunogenicity.",2011 Jun 15,"['Salvador, Aiala', 'Igartua, Manoli', 'Hernández, Rosa Maria', 'Pedraz, José Luis']",J Drug Deliv,,,True
f81a3ef89c4144309cf86374440e2a3a8a0e095c,PMC,Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony,http://dx.doi.org/10.1371/journal.ppat.1002155,PMC3136464,21779173,CC BY,"Adenoviruses are DNA viruses that naturally infect many vertebrates, including humans and monkeys, and cause a wide range of clinical illnesses in humans. Infection from individual strains has conventionally been thought to be species-specific. Here we applied the Virochip, a pan-viral microarray, to identify a novel adenovirus (TMAdV, titi monkey adenovirus) as the cause of a deadly outbreak in a closed colony of New World monkeys (titi monkeys; Callicebus cupreus) at the California National Primate Research Center (CNPRC). Among 65 titi monkeys housed in a building, 23 (34%) developed upper respiratory symptoms that progressed to fulminant pneumonia and hepatitis, and 19 of 23 monkeys, or 83% of those infected, died or were humanely euthanized. Whole-genome sequencing of TMAdV revealed that this adenovirus is a new species and highly divergent, sharing <57% pairwise nucleotide identity with other adenoviruses. Cultivation of TMAdV was successful in a human A549 lung adenocarcinoma cell line, but not in primary or established monkey kidney cells. At the onset of the outbreak, the researcher in closest contact with the monkeys developed an acute respiratory illness, with symptoms persisting for 4 weeks, and had a convalescent serum sample seropositive for TMAdV. A clinically ill family member, despite having no contact with the CNPRC, also tested positive, and screening of a set of 81 random adult blood donors from the Western United States detected TMAdV-specific neutralizing antibodies in 2 individuals (2/81, or 2.5%). These findings raise the possibility of zoonotic infection by TMAdV and human-to-human transmission of the virus in the population. Given the unusually high case fatality rate from the outbreak (83%), it is unlikely that titi monkeys are the native host species for TMAdV, and the natural reservoir of the virus is still unknown. The discovery of TMAdV, a novel adenovirus with the capacity to infect both monkeys and humans, suggests that adenoviruses should be monitored closely as potential causes of cross-species outbreaks.",2011 Jul 14,"['Chen, Eunice C.', 'Yagi, Shigeo', 'Kelly, Kristi R.', 'Mendoza, Sally P.', 'Maninger, Nicole', 'Rosenthal, Ann', 'Spinner, Abigail', 'Bales, Karen L.', 'Schnurr, David P.', 'Lerche, Nicholas W.', 'Chiu, Charles Y.']",PLoS Pathog,,,True
5c364a85b8e920e9b4ad2fa201589fc319bc174b,PMC,Interplay between SIN3A and STAT3 Mediates Chromatin Conformational Changes and GFAP Expression during Cellular Differentiation,http://dx.doi.org/10.1371/journal.pone.0022018,PMC3136934,21779366,CC BY,"BACKGROUND: Neurons and astrocytes are generated from common neural precursors, yet neurogenesis precedes astrocyte formation during embryogenesis. The mechanisms of neural development underlying suppression and de-suppression of differentiation- related genes for cell fate specifications are not well understood. METHODOLOGY/PRINCIPAL FINDINGS: By using an in vitro system in which NTera-2 cells were induced to differentiate into an astrocyte-like lineage, we revealed a novel role for Sin3A in maintaining the suppression of GFAP in NTera-2 cells. Sin3A coupled with MeCP2 bound to the GFAP promoter and their occupancies were correlated with repression of GFAP transcription. The repression by Sin3A and MeCP2 may be an essential mechanism underlying the inhibition of cell differentiation. Upon commitment toward an astrocyte-like lineage, Sin3A- MeCP2 departed from the promoter and activated STAT3 simultaneously bound to the promoter and exon 1 of GFAP; meanwhile, olig2 was exported from nuclei to the cytoplasm. This suggested that a three-dimensional or higher-order structure was provoked by STAT3 binding between the promoter and proximal coding regions. STAT3 then recruited CBP/p300 to exon 1 and targeted the promoter for histone H3K9 and H3K14 acetylation. The CBP/p300-mediated histone modification further facilitates chromatin remodeling, thereby enhancing H3K4 trimethylation and recruitment of RNA polymerase II to activate GFAP gene transcription. CONCLUSIONS/SIGNIFICANCE: These results provide evidence that exchange of repressor and activator complexes and epigenetic modifications are critical strategies for cellular differentiation and lineage-specific gene expression.",2011 Jul 11,"['Cheng, Pei-Yi', 'Lin, Yu-Ping', 'Chen, Ya-Ling', 'Lee, Yi-Ching', 'Tai, Chia-Chen', 'Wang, Yi-Ting', 'Chen, Yu-Ju', 'Kao, Cheng-Fu', 'Yu, John']",PLoS One,,,True
d87f44c7d76e4c51ed8e72103669c275e2db3e71,PMC,Milk Lacking α-Casein Leads to Permanent Reduction in Body Size in Mice,http://dx.doi.org/10.1371/journal.pone.0021775,PMC3138747,21789179,CC BY,"The major physiological function of milk is the transport of amino acids, carbohydrates, lipids and minerals to mammalian offspring. Caseins, the major milk proteins, are secreted in the form of a micelle consisting of protein and calcium-phosphate. We have analysed the role of the milk protein α-casein by inactivating the corresponding gene in mice. Absence of α-casein protein significantly curtails secretion of other milk proteins and calcium-phosphate, suggesting a role for α-casein in the establishment of casein micelles. In contrast, secretion of albumin, which is not synthesized in the mammary epithelium, into milk is not reduced. The absence of α-casein also significantly inhibits transcription of the other casein genes. α-Casein deficiency severely delays pup growth during lactation and results in a life-long body size reduction compared to control animals, but has only transient effects on physical and behavioural development of the pups. The data support a critical role for α-casein in casein micelle assembly. The results also confirm lactation as a critical window of metabolic programming and suggest milk protein concentration as a decisive factor in determining adult body weight.",2011 Jul 18,"['Kolb, Andreas F.', 'Huber, Reinhard C.', 'Lillico, Simon G.', 'Carlisle, Ailsa', 'Robinson, Claire J.', 'Neil, Claire', 'Petrie, Linda', 'Sorensen, Dorte B.', 'Olsson, I. Anna S.', 'Whitelaw, C. Bruce A.']",PLoS One,,,True
b5e8c704bc997577cfb950adffa06c7019aacf4a,PMC,Discovery of a small arterivirus gene that overlaps the GP5 coding sequence and is important for virus production,http://dx.doi.org/10.1099/vir.0.029264-0,PMC3139419,21307223,CC BY,"The arterivirus family (order Nidovirales) of single-stranded, positive-sense RNA viruses includes porcine respiratory and reproductive syndrome virus and equine arteritis virus (EAV). Their replicative enzymes are translated from their genomic RNA, while their seven structural proteins are encoded by a set of small, partially overlapping genes in the genomic 3′-proximal region. The latter are expressed via synthesis of a set of subgenomic mRNAs that, in general, are functionally monocistronic (except for a bicistronic mRNA encoding the E and GP2 proteins). ORF5, which encodes the major glycoprotein GP5, has been used extensively for phylogenetic analyses. However, an in-depth computational analysis now reveals the arterivirus-wide conservation of an additional AUG-initiated ORF, here termed ORF5a, that overlaps the 5′ end of ORF5. The pattern of substitutions across sequence alignments indicated that ORF5a is subject to functional constraints at the amino acid level, while an analysis of substitutions at synonymous sites in ORF5 revealed a greatly reduced frequency of substitution in the portion of ORF5 that is overlapped by ORF5a. The 43–64 aa ORF5a protein and GP5 are probably expressed from the same subgenomic mRNA, via a translation initiation mechanism involving leaky ribosomal scanning. Inactivation of ORF5a expression by reverse genetics yielded a severely crippled EAV mutant, which displayed lower titres and a tiny plaque phenotype. These defects, which could be partially complemented in ORF5a-expressing cells, indicate that the novel protein, which may be the eighth structural protein of arteriviruses, is expressed and important for arterivirus infection.",2011 May,"['Firth, Andrew E.', 'Zevenhoven-Dobbe, Jessika C.', 'Wills, Norma M.', 'Go, Yun Young', 'Balasuriya, Udeni B. R.', 'Atkins, John F.', 'Snijder, Eric J.', 'Posthuma, Clara C.']",J Gen Virol,,,True
1d8b7f079d5b7a6f9ecd1a0999f16582df84fd8e,PMC,NTPase and 5′-RNA Triphosphatase Activities of Chikungunya Virus nsP2 Protein,http://dx.doi.org/10.1371/journal.pone.0022336,PMC3139623,21811589,CC BY,"Chikungunya virus (CHIKV) is an insect borne virus (genus: Alphavirus) which causes acute febrile illness in humans followed by a prolonged arthralgic disease that affects the joints of the extremities. Re-emergence of the virus in the form of outbreaks in last 6–7 years has posed a serious public health problem. CHIKV has a positive sense single stranded RNA genome of about 12,000 nt. Open reading frame 1 of the viral genome encodes a polyprotein precursor, nsP1234, which is processed further into different non structural proteins (nsP1, nsP2, nsP3 and nsP4). Sequence based analyses have shown helicase domain at the N-terminus and protease domain at C-terminus of nsP2. A detailed biochemical analysis of NTPase/RNA helicase and 5′-RNA phosphatase activities of recombinant CHIKV-nsP2T protein (containing conserved NTPase/helicase motifs in the N-terminus and partial papain like protease domain at the C-terminus) was carried out. The protein could hydrolyze all NTPs except dTTP and showed better efficiency for ATP, dATP, GTP and dGTP hydrolysis. ATP was the most preferred substrate by the enzyme. CHIKV-nsP2T also showed 5′-triphosphatase (RTPase) activity that specifically removes the γ-phosphate from the 5′ end of RNA. Both NTPase and RTPase activities of the protein were completely dependent on Mg(2+) ions. RTPase activity was inhibited by ATP showing sharing of the binding motif by NTP and RNA. Both enzymatic activities were drastically reduced by mutations in the NTP binding motif (GKT) and co-factor, Mg(2+) ion binding motif (DEXX) suggesting that they have a common catalytic site.",2011 Jul 19,"['Karpe, Yogesh A.', 'Aher, Pankaj P.', 'Lole, Kavita S.']",PLoS One,,,True
fd9051e7bcf001955cb7625a5b2c51ddf58218dc,PMC,Interferon Production and Signaling Pathways Are Antagonized during Henipavirus Infection of Fruit Bat Cell Lines,http://dx.doi.org/10.1371/journal.pone.0022488,PMC3139658,21811620,CC BY,"Bats are natural reservoirs for a spectrum of infectious zoonotic diseases including the recently emerged henipaviruses (Hendra and Nipah viruses). Henipaviruses have been observed both naturally and experimentally to cause serious and often fatal disease in many different mammal species, including humans. Interestingly, infection of the flying fox with henipaviruses occurs in the absence of clinical disease. The extreme variation in the disease pattern between humans and bats has led to an investigation into the effects of henipavirus infection on the innate immune response in bat cell lines. We report that henipavirus infection does not result in the induction of interferon expression, and the viruses also inhibit interferon signaling. We also confirm that the interferon production and signaling block in bat cells is not due to differing viral protein expression levels between human and bat hosts. This information, in addition to the known lack of clinical signs in bats following henipavirus infection, suggests that bats control henipavirus infection by an as yet unidentified mechanism, not via the interferon response. This is the first report of henipavirus infection in bat cells specifically investigating aspects of the innate immune system.",2011 Jul 19,"['Virtue, Elena R.', 'Marsh, Glenn A.', 'Baker, Michelle L.', 'Wang, Lin-Fa']",PLoS One,,,True
c754ce4a15d6efa184842b77848e34d04445e209,PMC,Parasites or Cohabitants: Cruel Omnipresent Usurpers or Creative “Éminences Grises”?,http://dx.doi.org/10.1155/2011/214174,PMC3140032,21785696,CC BY,"This paper presents many types of interplays between parasites and the host, showing the history of parasites, the effects of parasites on the outcome of wars, invasions, migrations, and on the development of numerous regions of the globe, and the impact of parasitic diseases on the society and on the course of human evolution. It also emphasizes the pressing need to change the look at the parasitism phenomenon, proposing that the term “cohabitant” is more accurate than parasite, because every living being, from bacteria to mammals, is a consortium of living beings in the pangenome. Even the term parasitology should be replaced by cohabitology because there is no parasite alone and host alone: both together compose a new adaptive system: the parasitized-host or the cohabitant-cohabited being. It also suggests switching the old paradigm based on attrition and destruction, to a new one founded on adaptation and living together.",2011 Jul 18,"['Vannier-Santos, Marcos A.', 'Lenzi, Henrique L.']",J Parasitol Res,,,True
57ef6bf1ad8360243bf77eb91ed13430e42b35e1,PMC,Microbial Virulence as an Emergent Property: Consequences and Opportunities,http://dx.doi.org/10.1371/journal.ppat.1002136,PMC3141035,21814511,CC BY,,2011 Jul 21,"['Casadevall, Arturo', 'Fang, Ferric C.', 'Pirofski, Liise-anne']",PLoS Pathog,,,True
8ef53001824bab46d02f6968b8ee1a148a7406d9,PMC,Global mRNA Degradation during Lytic Gammaherpesvirus Infection Contributes to Establishment of Viral Latency,http://dx.doi.org/10.1371/journal.ppat.1002150,PMC3141057,21811408,CC BY,"During a lytic gammaherpesvirus infection, host gene expression is severely restricted by the global degradation and altered 3′ end processing of mRNA. This host shutoff phenotype is orchestrated by the viral SOX protein, yet its functional significance to the viral lifecycle has not been elucidated, in part due to the multifunctional nature of SOX. Using an unbiased mutagenesis screen of the murine gammaherpesvirus 68 (MHV68) SOX homolog, we isolated a single amino acid point mutant that is selectively defective in host shutoff activity. Incorporation of this mutation into MHV68 yielded a virus with significantly reduced capacity for mRNA turnover. Unexpectedly, the MHV68 mutant showed little defect during the acute replication phase in the mouse lung. Instead, the virus exhibited attenuation at later stages of in vivo infections suggestive of defects in both trafficking and latency establishment. Specifically, mice intranasally infected with the host shutoff mutant accumulated to lower levels at 10 days post infection in the lymph nodes, failed to develop splenomegaly, and exhibited reduced viral DNA levels and a lower frequency of latently infected splenocytes. Decreased latency establishment was also observed upon infection via the intraperitoneal route. These results highlight for the first time the importance of global mRNA degradation during a gammaherpesvirus infection and link an exclusively lytic phenomenon with downstream latency establishment.",2011 Jul 21,"['Richner, Justin M.', 'Clyde, Karen', 'Pezda, Andrea C.', 'Cheng, Benson Yee Hin', 'Wang, Tina', 'Kumar, G. Renuka', 'Covarrubias, Sergio', 'Coscoy, Laurent', 'Glaunsinger, Britt']",PLoS Pathog,,,True
795711186071a762e389ea991737dbc51abf8d41,PMC,Global mRNA Degradation during Lytic Gammaherpesvirus Infection Contributes to Establishment of Viral Latency,http://dx.doi.org/10.1371/journal.ppat.1002150,PMC3141057,21811408,CC BY,"During a lytic gammaherpesvirus infection, host gene expression is severely restricted by the global degradation and altered 3′ end processing of mRNA. This host shutoff phenotype is orchestrated by the viral SOX protein, yet its functional significance to the viral lifecycle has not been elucidated, in part due to the multifunctional nature of SOX. Using an unbiased mutagenesis screen of the murine gammaherpesvirus 68 (MHV68) SOX homolog, we isolated a single amino acid point mutant that is selectively defective in host shutoff activity. Incorporation of this mutation into MHV68 yielded a virus with significantly reduced capacity for mRNA turnover. Unexpectedly, the MHV68 mutant showed little defect during the acute replication phase in the mouse lung. Instead, the virus exhibited attenuation at later stages of in vivo infections suggestive of defects in both trafficking and latency establishment. Specifically, mice intranasally infected with the host shutoff mutant accumulated to lower levels at 10 days post infection in the lymph nodes, failed to develop splenomegaly, and exhibited reduced viral DNA levels and a lower frequency of latently infected splenocytes. Decreased latency establishment was also observed upon infection via the intraperitoneal route. These results highlight for the first time the importance of global mRNA degradation during a gammaherpesvirus infection and link an exclusively lytic phenomenon with downstream latency establishment.",2011 Jul 21,"['Richner, Justin M.', 'Clyde, Karen', 'Pezda, Andrea C.', 'Cheng, Benson Yee Hin', 'Wang, Tina', 'Kumar, G. Renuka', 'Covarrubias, Sergio', 'Coscoy, Laurent', 'Glaunsinger, Britt']",PLoS Pathog,,,False
23acad3bdcee7563f22da647aae639dbee1d56e6,PMC,Equal Graph Partitioning on Estimated Infection Network as an Effective Epidemic Mitigation Measure,http://dx.doi.org/10.1371/journal.pone.0022124,PMC3142118,21799777,CC BY,"Controlling severe outbreaks remains the most important problem in infectious disease area. With time, this problem will only become more severe as population density in urban centers grows. Social interactions play a very important role in determining how infectious diseases spread, and organization of people along social lines gives rise to non-spatial networks in which the infections spread. Infection networks are different for diseases with different transmission modes, but are likely to be identical or highly similar for diseases that spread the same way. Hence, infection networks estimated from common infections can be useful to contain epidemics of a more severe disease with the same transmission mode. Here we present a proof-of-concept study demonstrating the effectiveness of epidemic mitigation based on such estimated infection networks. We first generate artificial social networks of different sizes and average degrees, but with roughly the same clustering characteristic. We then start SIR epidemics on these networks, censor the simulated incidences, and use them to reconstruct the infection network. We then efficiently fragment the estimated network by removing the smallest number of nodes identified by a graph partitioning algorithm. Finally, we demonstrate the effectiveness of this targeted strategy, by comparing it against traditional untargeted strategies, in slowing down and reducing the size of advancing epidemics.",2011 Jul 22,"['Hadidjojo, Jeremy', 'Cheong, Siew Ann']",PLoS One,,,True
80a8911f3ccc06ddfc7581569014032487688283,PMC,Reference gene selection for gene expression studies using RT-qPCR in virus-infected planthoppers,http://dx.doi.org/10.1186/1743-422X-8-308,PMC3142240,21679431,CC BY,"BACKGROUND: Planthoppers not only severely affect crops by causing mechanical damage when feeding but are also vectors of several plant virus species. The analysis of gene expression in persistently infected planthoppers might unveil the molecular basis of viral transmission. Quantitative real-time RT-PCR (RT-qPCR) is currently the most accurate and sensitive method used for quantitative gene expression analysis. In order to normalize the resulting quantitative data, reference genes with constant expression during the experimental procedures are needed. RESULTS: Partial sequences of the commonly used reference genes actin (ACT), α1-tubulin (TUB), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), elongation factor 1 alpha (EF1A), ribosomal protein S18 (RPS18) and polyubiquitin C (UBI) from Delphacodes kuscheli, a planthopper capable of persistently transmitting the plant fijivirus Mal de Río Cuarto virus (MRCV), were isolated for the first time. Specific RT-qPCR primers were designed and the expression stability of these genes was assayed in MRCV-infective and naïve planthoppers using geNorm, Normfinder and BestKeeper tools. The overall analysis showed that UBI, followed by 18S and ACT, are the most suitable genes as internal controls for quantitative gene expression studies in MRCV-infective planthoppers, while TUB and EF1A are the most variable ones. Moreover, EF1A was upregulated by MRCV infection. CONCLUSIONS: A RT-qPCR platform for gene expression analysis in the MRCV-infected planthopper vector Delphacodes kuscheli was developed. Our work is the first report on reference gene selection in virus-infected insects, and might serve as a precedent for future gene expression studies on MRCV and other virus-planthopper pathosystems.",2011 Jun 16,"['Maroniche, Guillermo A', 'Sagadín, Mónica', 'Mongelli, Vanesa C', 'Truol, Graciela A', 'del Vas, Mariana']",Virol J,,,True
e1406defdf36c0e9507a509d880dd7df0ed84f56,PMC,On the Treatment of Airline Travelers in Mathematical Models,http://dx.doi.org/10.1371/journal.pone.0022151,PMC3143116,21799782,CC0,"The global spread of infectious diseases is facilitated by the ability of infected humans to travel thousands of miles in short time spans, rapidly transporting pathogens to distant locations. Mathematical models of the actual and potential spread of specific pathogens can assist public health planning in the case of such an event. Models should generally be parsimonious, but must consider all potentially important components of the system to the greatest extent possible. We demonstrate and discuss important assumptions relative to the parameterization and structural treatment of airline travel in mathematical models. Among other findings, we show that the most common structural treatment of travelers leads to underestimation of the speed of spread and that connecting travel is critical to a realistic spread pattern. Models involving travelers can be improved significantly by relatively simple structural changes but also may require further attention to details of parameterization.",2011 Jul 25,"['Johansson, Michael A.', 'Arana-Vizcarrondo, Neysarí', 'Biggerstaff, Brad J.', 'Staples, J. Erin', 'Gallagher, Nancy', 'Marano, Nina']",PLoS One,,,True
1fb48248ba087b62ed753f63f4ff046e68828bf9,PMC,Redesigning a large school-based clinical trial in response to                     changes in community practice,http://dx.doi.org/10.1177/1740774511403513,PMC3145214,21730079,CC BY,"Background Asthma exacerbations are seasonal with the greatest risk in elementary-age students occurring shortly after returning to school following summer break. Recent research suggests that this seasonality in children is primarily related to viral respiratory tract infections. Regular hand washing is the most effective method to prevent the spread of viral respiratory infections; unfortunately, achieving hand washing recommendations in schools is difficult. Therefore, we designed a study to evaluate the effect of hand sanitizer use in elementary schools on exacerbations among children with asthma. Purpose To describe the process of redesigning the trial in response to changes in the safety profile of the hand sanitizer as well as changes in hand hygiene practice in the schools. Methods The original trial was a randomized, longitudinal, subject-blinded, placebo-controlled, community-based crossover trial. The primary aim was to evaluate the incremental effectiveness of hand sanitizer use in addition to usual hand hygiene practices to decrease asthma exacerbations in elementary-age children. Three events occurred that required major modifications to the original study protocol: (1) safety concerns arose regarding the hand sanitizer’s active ingredient; (2) no substitute placebo hand sanitizer was available; and (3) community preferences changed regarding hand hygiene practices in the schools. Results The revised protocol is a randomized, longitudinal, community-based crossover trial. The primary aim is to evaluate the incremental effectiveness of a two-step hand hygiene process (hand hygiene education plus institutionally provided alcohol-based hand sanitizer) versus usual care to decrease asthma exacerbations. Enrollment was completed in May 2009 with 527 students from 30 schools. The intervention began in August 2009 and will continue through May 2011. Study results should be available at the end of 2011. Limitations The changed design does not allow us to directly measure the effectiveness of hand sanitizer use as a supplement to traditional hand washing practices. Conclusions The need to balance a rigorous study design with one that is acceptable to the community requires investigators to be actively involved with community collaborators and able to adapt study protocols to fit changing community practices.",2011 Jun,"['Gerald, Lynn B', 'Gerald, Joe K', 'McClure, Leslie A', 'Harrington, Kathy', 'Erwin, Sue', 'Bailey, William C']",Clin Trials,,,True
f9572dc31ce0512cc966d43fbe693656af18a03c,PMC,Immunity Traits in Pigs: Substantial Genetic Variation and Limited Covariation,http://dx.doi.org/10.1371/journal.pone.0022717,PMC3146468,21829490,CC BY,"BACKGROUND: Increasing robustness via improvement of resistance to pathogens is a major selection objective in livestock breeding. As resistance traits are difficult or impossible to measure directly, potential indirect criteria are measures of immune traits (ITs). Our underlying hypothesis is that levels of ITs with no focus on specific pathogens define an individual's immunocompetence and thus predict response to pathogens in general. Since variation in ITs depends on genetic, environmental and probably epigenetic factors, our aim was to estimate the relative importance of genetics. In this report, we present a large genetic survey of innate and adaptive ITs in pig families bred in the same environment. METHODOLOGY/PRINCIPAL FINDINGS: Fifty four ITs were studied on 443 Large White pigs vaccinated against Mycoplasma hyopneumoniae and analyzed by combining a principal component analysis (PCA) and genetic parameter estimation. ITs include specific and non specific antibodies, seric inflammatory proteins, cell subsets by hemogram and flow cytometry, ex vivo production of cytokines (IFNα, TNFα, IL6, IL8, IL12, IFNγ, IL2, IL4, IL10), phagocytosis and lymphocyte proliferation. While six ITs had heritabilities that were weak or not significantly different from zero, 18 and 30 ITs had moderate (0.1<h2≤0.4) or high (h2>0.4) heritability values, respectively. Phenotypic and genetic correlations between ITs were weak except for a few traits that mostly include cell subsets. PCA revealed no cluster of innate or adaptive ITs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that variation in many innate and adaptive ITs is genetically controlled in swine, as already reported for a smaller number of traits by other laboratories. A limited redundancy of the traits was also observed confirming the high degree of complementarity between innate and adaptive ITs. Our data provide a genetic framework for choosing ITs to be included as selection criteria in multitrait selection programmes that aim to improve both production and health traits.",2011 Jul 29,"['Flori, Laurence', 'Gao, Yu', 'Laloë, Denis', 'Lemonnier, Gaëtan', 'Leplat, Jean-Jacques', 'Teillaud, Angélique', 'Cossalter, Anne-Marie', 'Laffitte, Joëlle', 'Pinton, Philippe', 'de Vaureix, Christiane', 'Bouffaud, Marcel', 'Mercat, Marie-José', 'Lefèvre, François', 'Oswald, Isabelle P.', 'Bidanel, Jean-Pierre', 'Rogel-Gaillard, Claire']",PLoS One,,,True
f87f39187b751fafb24dad2685376da7c78f79e2,PMC,Accelerating vaccine development and deployment: report of a Royal Society satellite meeting,http://dx.doi.org/10.1098/rstb.2011.0100,PMC3146780,21893549,CC BY,"The Royal Society convened a meeting on the 17th and 18th November 2010 to review the current ways in which vaccines are developed and deployed, and to make recommendations as to how each of these processes might be accelerated. The meeting brought together academics, industry representatives, research sponsors, regulators, government advisors and representatives of international public health agencies from a broad geographical background. Discussions were held under Chatham House rules. High-throughput screening of new vaccine antigens and candidates was seen as a driving force for vaccine discovery. Multi-stakeholder, small-scale manufacturing facilities capable of rapid production of clinical grade vaccines are currently too few and need to be expanded. In both the human and veterinary areas, there is a need for tiered regulatory standards, differentially tailored for experimental and commercial vaccines, to allow accelerated vaccine efficacy testing. Improved cross-fertilization of knowledge between industry and academia, and between human and veterinary vaccine developers, could lead to more rapid application of promising approaches and technologies to new product development. Identification of best-practices and development of checklists for product development plans and implementation programmes were seen as low-cost opportunities to shorten the timeline for vaccine progression from the laboratory bench to the people who need it.",2011 Oct 12,"['Bregu, Migena', 'Draper, Simon J.', 'Hill, Adrian V. S.', 'Greenwood, Brian M.']",Philos Trans R Soc Lond B Biol Sci,,,False
c7f717457621e576d69c56b61d9ad9bd52a8a8b5,PMC,"During the summer 2009 outbreak of ""swine flu"" in Scotland what respiratory pathogens were diagnosed as H1N1/2009?",http://dx.doi.org/10.1186/1471-2334-11-192,PMC3146830,21752259,CC BY,"BACKGROUND: During the April-July 2009 outbreak of H1N1/2009 in scotland the West of Scotland Specialist Virology Centre (WoSSVC) in Glasgow tested > 16 000 clinical samples for H1N1/2009. Most were from patients clinically diagnosed with H1N1/2009. Out of these, 9% were positive. This study sought to determine what respiratory pathogens were misdiagnosed as cases of H1N1/2009 during this time. METHODS: We examined the results from 3247 samples which were sent to the laboratory during April-July 2009. All were from patients clinically diagnosed as having H1N1/2009 (based on accepted criteria) and all were given a full respiratory screen using real time reverse transcriptase polymerase chain reaction (rtRT-PCR) assays. RESULTS: In total, respiratory pathogens were detected in 27.9% (95% confidence interval, 26.3-29.5%) of the samples submitted. Numerous pathogens were detected, the most common of which were rhinovirus (8.9% (95% confidence interval, 7.9-9.9%)), parainfluenza 1 (1.9% (95% confidence interval, 1.4-2.4%)) and 3 (4.1% (95% confidence interval, 3.3-4.9%)), and adenovirus ((3.5% (95% confidence interval, 2.9-4.2%)). CONCLUSIONS: This study highlights the problems of using a clinical algorithm to detect H1N1/2009. Clinicians frequently misdiagnosed common respiratory pathogens as H1N1/2009 during the spring/summer outbreak in Scotland. Many undesirable consequences would have resulted, relating to treatment, infection control, and public health surveillance.",2011 Jul 13,"['Gunson, Rory N', 'Carman, William F']",BMC Infect Dis,,,True
d9006d571ae04afb914b4bdd5c32f2090d409b4c,PMC,Agent-based simulation for weekend-extension strategies to mitigate influenza outbreaks,http://dx.doi.org/10.1186/1471-2458-11-522,PMC3146865,21718518,CC BY,"BACKGROUND: Non-pharmaceutical strategies are vital in curtailing impacts of influenza and have been intensively studied in public health. However, few strategies have explicitly utilized the weekend effect, which has been widely reported to be capable of reducing influenza infections. This study aims to explore six weekend-extension strategies against seasonal and pandemic flu outbreaks. METHODS: The weekend-extension strategies were designed to extend regular two-day weekend by one, two and three days, respectively, and in combination with either a continuous or discontinuous pattern. Their effectiveness was evaluated using an established agent-based spatially explicit simulation model in the urbanized area of Buffalo, NY, US. RESULTS: If the extensions last more than two days, the weekend-extension strategies can remarkably reduce the overall disease attack rate of seasonal flu. Particularly, a three-day continuous extension is sufficient to suppress the epidemic and confine the spread of disease. For the pandemic flu, the weekend-extension strategies only produce a few mitigation effects until the extensions exceed three days. Sensitivity analysis indicated that a compliance level above 75% is necessary for the weekend-extension strategies to take effects. CONCLUSION: This research is the first attempt to incorporate the weekend effect into influenza mitigation strategies. The results suggest that appropriate extensions of the regular two-day weekend can be a potential measure to fight against influenza outbreaks, while minimizing interruptions on normal rhythms of socio-economy. The concept of weekend extension would be particularly useful if there were a lack of vaccine stockpiles, e.g., in countries with limited health resources, or in the case of unknown emerging infectious diseases.",2011 Jun 30,"Mao, Liang",BMC Public Health,,,True
47fb645312a069e65bb7557c58204244c3c92953,PMC,Immunoproteomic analysis of bacterial proteins of Actinobacillus pleuropneumoniae serotype 1,http://dx.doi.org/10.1186/1477-5956-9-32,PMC3148531,21703014,CC BY,"BACKGROUND: Actinobacillus pleuropneumoniae (APP) is one of the most important swine pathogens worldwide. Identification and characterization of novel antigenic APP vaccine candidates are underway. In the present study, we use an immunoproteomic approach to identify APP protein antigens that may elicit an immune response in serotype 1 naturally infected swine and serotype 1 virulent strain S259-immunized rabbits. RESULTS: Proteins from total cell lysates of serotype 1 APP were separated by two-dimensional electrophoresis (2DE). Western blot analysis revealed 21 immunoreactive protein spots separated in the pH 4-7 range and 4 spots in the pH 7-11 range with the convalescent sera from swine; we found 5 immunoreactive protein spots that separated in the pH 4-7 range and 2 in the pH 7-11 range with hyperimmune sera from S259-immunized rabbits. The proteins included the known antigens ApxIIA, protective surface antigen D15, outer membrane proteins P5, subunit NqrA. The remaining antigens are being reported as immunoreactive proteins in APP for the first time, to our knowledge. CONCLUSIONS: We identified a total of 42 immunoreactive proteins of the APP serotype 1 virulent strain S259 which represented 32 different proteins, including some novel immunoreactive factors which could be researched as vaccine candidates.",2011 Jun 26,"['Zhang, Wei', 'Shao, Jing', 'Liu, Guangjin', 'Tang, Fang', 'Lu, Yan', 'Zhai, Zhipeng', 'Wang, Yang', 'Wu, Zongfu', 'Yao, Huochun', 'Lu, Chengping']",Proteome Sci,,,True
a730b4d5a5a0353503a1cd46d458635f93618805,PMC,Compare the differences of synonymous codon usage between the two species within cardiovirus,http://dx.doi.org/10.1186/1743-422X-8-325,PMC3148564,21708006,CC BY,"BACKGROUND: Cardioviruses are positive-strand RNA viruses in the Picornaviridae family that can cause enteric infection in rodents and also been detected at lower frequencies in other mammals such as pigs and human beings. The Cardiovirus genus consists two distinct species: Encephalomyocarditis virus (EMCV) and Theilovirus (ThV). There are a lot differences between the two species. In this study, the differences of codon usage in EMCV and ThV were compared. RESULTS: The mean ENC values of EMCV and ThV are 54.86 and 51.08 respectively, higher than 40.And there are correlations between (C+G)(12)% and (C+G)(3)% for both EMCV and ThV (r = -0.736;r = 0.986, P < 0.01, repectively). For ThV the (C+G)(12)%, (C+G)(3)%, axis f'(1 )and axis f'(2 )had a significant correlations respectively but not for EMCV. According to the RSCU values, the EMCV species seemed to prefer U, G and C ending codon, while the ThV spice seemed to like using U and A ending codon. However, in both genus AGA for Arg, AUU for Ile, UCU for Ser, and GGA for Gly were chosen preferentially. Correspondence analysis detected one major trend in the first axis (f'(1)) which accounted for 22.89% of the total variation, and another major trend in the second axis (f'(2)) which accounted for 17.64% of the total variation. And the plots of the same serotype seemed at the same region at the coordinate. CONCLUSION: The overall extents of codon usage bias in both EMCV and ThV are low. The mutational pressure is the main factor that determines the codon usage bias, but the (C+G) content plays a more important role in codon usage bias for ThV than for EMCV. The synonymous codon usage pattern in both EMCV and ThV genes is gene function and geography specific, but not host specific. Maybe the serotype is one factor effected the codon bias for ThV, and location has no significant effect on the variations of synonymous codon usage in these virus genes.",2011 Jun 27,"['Liu, Wen-qian', 'Zhang, Jie', 'Zhang, Yi-qiang', 'Zhou, Jian-hua', 'Chen, Hao-tai', 'Ma, Li-na', 'Ding, Yao-zhong', 'Liu, Yongsheng']",Virol J,,,True
121638b718d18f7bb5086223540f74cf61e49800,PMC,Severe community-acquired adenovirus pneumonia in an immunocompetent 44-year-old woman: a case report and review of the literature,http://dx.doi.org/10.1186/1752-1947-5-259,PMC3148995,21718493,CC BY,"INTRODUCTION: This case report describes a rare condition: community-acquired adenovirus pneumonia in an immunocompetent adult. The diagnosis was achieved by using a multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay and highlights the usefulness of these novel molecular diagnostic techniques in patients hospitalized with acute respiratory illness. We also performed a literature search for previously published cases and present a summary of the clinical, laboratory and radiological features of this condition. CASE PRESENTATION: A 44-year-old immunocompetent Caucasian woman was admitted to our hospital with an acute febrile respiratory illness associated with a rash. Her blood tests were non-specifically abnormal, and tests for bacterial pathogens were negative. Her condition rapidly deteriorated while she was in our hospital and required mechanical ventilation and inotropic support. A multiplex real-time RT-PCR assay performed on respiratory specimens to detect respiratory viruses was negative for influenza but positive for adenovirus DNA. The patient recovered on supportive treatment, and antibiotics were stopped after 5 days. CONCLUSIONS: Community-acquired adenovirus pneumonia in immunocompetent adult civilians presents as a non-specific acute febrile respiratory illness followed by the abrupt onset of respiratory failure, often requiring mechanical ventilation. Its laboratory and radiological features are typical of viral infections but also are non-specific. Novel multiplex real-time RT-PCR testing for respiratory viruses enabled us to rapidly make the diagnosis in this case. The new technology could be used more widely in patients with acute respiratory illness and has potential utility for rationalization of the use of antibiotics and improving infection control measures.",2011 Jun 30,"['Clark, Tristan W', 'Fleet, Daniel H', 'Wiselka, Martin J']",J Med Case Reports,,,True
7120211f7eda128e441ed22e3e4d8d3eda07b771,PMC,Effect of oral care gel on the quality of life for oral lichen planus in patients with chronic HCV infection,http://dx.doi.org/10.1186/1743-422X-8-348,PMC3149004,21749712,CC BY,"BACKGROUND: Oral lichen planus (OLP) decreases the quality of life because it can cause spontaneous pain during eating and tooth-brushing and an uncomfortable feeling in the mouth. In addition, OLP may be associated with HCV-related liver disease. We investigated the visual analogue scale (VAS) and effects of oral care gel, REFRECARE-H(®), on patients with OLP associated with HCV infection. RESULTS: Nine OLP patients (mean age 67.9 ± 7.6 years) with HCV-related liver diseases were recruited and their VAS score determined along with a biochemical examination of the blood. Types of OLP included erosive (6 patients) and reticular (3). REFRECARE-H(®), an oral care gel (therapeutic dentifrice) containing hinokitiol, was applied by each patient as a thin layer on the oral membrane, after each meal and at bedtime for 30 days. Application of REFRECARE-H(® )improved the quality of life in all terms of dry mouth, breath odor, oral freshness, oral pain during rest, oral pain at a mealtimes, taste disorder, loss of appetite, sleep disorder, depressive mood and jitteriness. VAS scores of dry mouth, breath odor, oral freshness, and sleep disorder were significantly increased 30 days after application of REFRECARE-H(® )(P = 0.01, P = 0.05, P = 0.03, P = 0.04). VAS scores of oral pain at a mealtimes and taste disorder were increased 30 days after application of REFRECARE-H(® )(P = 0.06). There was an absence of side effects. CONCLUSIONS: REFRECARE-H(® )improved the quality of life for OLP. It is necessary for the hepatologist to educate patients regarding oral hygiene, as well as provide treatment of liver disease.",2011 Jul 12,"['Nagao, Yumiko', 'Sata, Michio']",Virol J,,,True
24e8a04adeb7f1142768d4de1e10d8ac48afcd03,PMC,Investigation of Griffithsin's Interactions with Human Cells Confirms Its Outstanding Safety and Efficacy Profile as a Microbicide Candidate,http://dx.doi.org/10.1371/journal.pone.0022635,PMC3149051,21829638,CC0,"Many natural product-derived lectins such as the red algal lectin griffithsin (GRFT) have potent in vitro activity against viruses that display dense clusters of oligomannose N-linked glycans (NLG) on their surface envelope glycoproteins. However, since oligomannose NLG are also found on some host proteins it is possible that treatment with antiviral lectins may trigger undesirable side effects. For other antiviral lectins such as concanavalin A, banana lectin and cyanovirin-N (CV-N), interactions between the lectin and as yet undescribed cellular moieties have been reported to induce undesirable side effects including secretion of inflammatory cytokines and activation of host T-cells. We show that GRFT, unlike CV-N, binds the surface of human epithelial and peripheral blood mononuclear cells (PBMC) through an exclusively oligosaccharide-dependent interaction. In contrast to several other antiviral lectins however, GRFT treatment induces only minimal changes in secretion of inflammatory cytokines and chemokines by epithelial cells or human PBMC, has no measureable effect on cell viability and does not significantly upregulate markers of T-cell activation. In addition, GRFT appears to retain antiviral activity once bound to the surface of PBMC. Finally, RNA microarray studies show that, while CV-N and ConA regulate expression of a multitude of cellular genes, GRFT treatment effects only minimal alterations in the gene expression profile of a human ectocervical cell line. These studies indicate that GRFT has an outstanding safety profile with little evidence of induced toxicity, T-cell activation or deleterious immunological consequence, unique attributes for a natural product-derived lectin.",2011 Aug 2,"['Kouokam, Joseph Calvin', 'Huskens, Dana', 'Schols, Dominique', 'Johannemann, Andrew', 'Riedell, Shonna K.', 'Walter, Wendye', 'Walker, Janice M.', 'Matoba, Nobuyuki', ""O'Keefe, Barry R."", 'Palmer, Kenneth E.']",PLoS One,,,True
06589343cb2fcc62a39c587071c8a9e76836f993,PMC,Analysis of CDC social control measures using an agent-based simulation of an influenza epidemic in a city,http://dx.doi.org/10.1186/1471-2334-11-199,PMC3151229,21767379,CC BY,"BACKGROUND: The transmission of infectious disease amongst the human population is a complex process which requires advanced, often individual-based, models to capture the space-time details observed in reality. METHODS: An Individual Space-Time Activity-based Model (ISTAM) was applied to simulate the effectiveness of non-pharmaceutical control measures including: (1) refraining from social activities, (2) school closure and (3) household quarantine, for a hypothetical influenza outbreak in an urban area. RESULTS: Amongst the set of control measures tested, refraining from social activities with various compliance levels was relatively ineffective. Household quarantine was very effective, especially for the peak number of cases and total number of cases, with large differences between compliance levels. Household quarantine resulted in a decrease in the peak number of cases from more than 300 to around 158 for a 100% compliance level, a decrease of about 48.7%. The delay in the outbreak peak was about 3 to 17 days. The total number of cases decreased to a range of 3635-5403, that is, 63.7%-94.7% of the baseline value. When coupling control measures, household quarantine together with school closure was the most effective strategy. The resulting space-time distribution of infection in different classes of activity bundles (AB) suggests that the epidemic outbreak is strengthened amongst children and then spread to adults. By sensitivity analysis, this study demonstrated that earlier implementation of control measures leads to greater efficacy. Also, for infectious diseases with larger basic reproduction number, the effectiveness of non-pharmaceutical measures was shown to be limited. CONCLUSIONS: Simulated results showed that household quarantine was the most effective control measure, while school closure and household quarantine implemented together achieved the greatest benefit. Agent-based models should be applied in the future to evaluate the efficacy of control measures for a range of disease outbreaks in a range of settings given sufficient information about the given case and knowledge about the transmission processes at a fine scale.",2011 Jul 18,"['Yang, Yong', 'Atkinson, Peter M', 'Ettema, Dick']",BMC Infect Dis,,,True
4a0df4a0f4d88046442f66ad84ba40b2c34e2493,PMC,The Interaction of LFA-1 on Mononuclear Cells and ICAM-1 on Tubular Epithelial Cells Accelerates TGF-β1-Induced Renal Epithelial-Mesenchymal Transition,http://dx.doi.org/10.1371/journal.pone.0023267,PMC3151298,21850266,CC BY,"The epithelial-mesenchymal transition (EMT) of renal epithelial cells (RTECs) has pivotal roles in the development of renal fibrosis. Although the interaction of lymphocyte function-associated antigen 1 (LFA-1) on leukocytes and its ligand, intracellular adhesion molecule 1 (ICAM-1), plays essential roles in most inflammatory reactions, its pathogenetic role in the EMT of RTECs remains to be clarified. In the present study, we investigated the effect of the interaction of LFA-1 on peripheral blood mononuclear cells (PBMCs) and ICAM-1 on HK-2 cells after stimulation with TGF-β(1) on the EMT of RTECs. ICAM-1 was highly expressed in HK-2 cells. After TGF-β(1) stimulation, the chemokines CCL3 and CXCL12 increased on HK-2 cells. After co-culture of PBMCs and HK-2 cells pre-stimulated with TGF-β(1) (0.1 ng/ml) (HK-2-TGF-β(1) (0.1)), the expression of the active form of LFA-1 increased on PBMCs; however, total LFA-1 expression did not change. The expression of the active form of LFA-1 on PBMCs did not increase after co-culture with not CCL3 but CXCL12 knockdown HK-2-TGF-β(1) (0.1). The expression of epithelial cell junction markers (E-cadherin and occludin) further decreased and that of mesenchymal markers (vimentin and fibronectin) further increased in HK-2-TGF-β(1) (0.1) after co-culture with PBMCs for 24 hrs (HK-2-TGF-β(1) (0.1)-PBMCs). The phosphorylation of ERK 1/2 but not smad2 and smad3 increased in HK-2-TGF-β(1) (0.1)-PBMCs. The snail and slug signaling did not increase HK-2-TGF-β(1) (0.1)-PBMCs. Although the migration and invasion of HK-2 cells induced full EMT by a high dose (10.0 ng/ml) and long-term (72–96 hrs) TGF-β(1) stimulation increased, that of HK-2-TGF-β(1) (0.1)-PBMCs did not increase. These results suggested that HK-2 cells stimulated with TGF-β(1) induced conformational activation of LFA-1 on PBMCs by increased CXCL12. Then, the direct interaction of LFA-1 on PBMCs and ICAM-1 on HK-2 cells activated ERK1/2 signaling to accelerate the part of EMT of HK-2 cells induced by TGF-β(1.)",2011 Aug 5,"['Morishita, Yoshiyuki', 'Watanabe, Minami', 'Nakazawa, Eiko', 'Ishibashi, Kenichi', 'Kusano, Eiji']",PLoS One,,,True
b87dbfb99e667d88cda4e153340b44404f7b4c98,PMC,Entry screening to delay local transmission of 2009 pandemic influenza A (H1N1),http://dx.doi.org/10.1186/1471-2334-10-82,PMC3152767,20353566,CC BY,"BACKGROUND: After the WHO issued the global alert for 2009 pandemic influenza A (H1N1), many national health agencies began to screen travelers on entry in airports, ports and border crossings to try to delay local transmission. METHODS: We reviewed entry screening policies adopted by different nations and ascertained dates of official report of the first laboratory-confirmed imported H1N1 case and the first laboratory-confirmed untraceable or 'local' H1N1 case. RESULTS: Implementation of entry screening policies was associated with on average additional 7-12 day delays in local transmission compared to nations that did not implement entry screening, with lower bounds of 95% confidence intervals consistent with no additional delays and upper bounds extending to 20-30 day additional delays. CONCLUSIONS: Entry screening may lead to short-term delays in local transmission of a novel strain of influenza virus. The resources required for implementation should be balanced against the expected benefits of entry screening.",2010 Mar 30,"['Cowling, Benjamin J', 'Lau, Lincoln LH', 'Wu, Peng', 'Wong, Helen WC', 'Fang, Vicky J', 'Riley, Steven', 'Nishiura, Hiroshi']",BMC Infect Dis,,,True
1ec08de8b92b3b6c9be98dcd92db0ddf3efdad44,PMC,Immunomodulator expression in trophoblasts from the feline immunodeficiency virus (FIV)-infected cat,http://dx.doi.org/10.1186/1743-422X-8-336,PMC3152912,21729293,CC BY,"BACKGROUND: FIV infection frequently compromises pregnancy under experimental conditions and is accompanied by aberrant expression of some placental cytokines. Trophoblasts produce numerous immunomodulators that play a role in placental development and pregnancy maintenance. We hypothesized that FIV infection may cause dysregulation of trophoblast immunomodulator expression, and aberrant expression of these molecules may potentiate inflammation and compromise pregnancy. The purpose of this project was to evaluate the expression of representative pro-(TNF-α, IFN-γ, IL-1β, IL-2, IL-6, IL-12p35, IL-12p40, IL-18, and GM-CSF) and anti-inflammatory cytokines (IL-4, IL-5, and IL-10); CD134, a secondary co-stimulatory molecule expressed on activated T cells (FIV primary receptor); the chemokine receptor CXCR4 (FIV co-receptor); SDF-1α, the chemokine ligand to CXCR4; and FIV gag in trophoblasts from early-and late-term pregnancy. METHODS: We used an anti-cytokeratin antibody in immunohistochemistry to identify trophoblasts selectively, collected these cells using laser capture microdissection, and extracted total RNA from the captured cell populations. Real time, reverse transcription-PCR was used to quantify gene expression. RESULTS: We detected IL-4, IL-5, IL-6, IL-1β, IL-12p35, IL-12p40, and CXCR4 in trophoblasts from early-and late-term pregnancy. Expression of cytokines increased from early to late pregnancy in normal tissues. A clear, pro-inflammatory microenvironment was not evident in trophoblasts from FIV-infected queens at either stage of pregnancy. Reproductive failure was accompanied by down-regulation of both pro-and anti-inflammatory cytokines. CD134 was not detected in trophoblasts, and FIV gag was detected in only one of ten trophoblast specimens collected from FIV-infected queens. CONCLUSION: Feline trophoblasts express an array of pro-and anti-inflammatory immunomodulators whose expression increases from early to late pregnancy in normal tissues. Non-viable pregnancies were associated with decreased expression of immunomodulators which regulate trophoblast invasion in other species. The detection of FIV RNA in trophoblasts was rare, suggesting that the high rate of reproductive failure in FIV-infected queens was not a direct result of viral replication in trophoblasts. The influence of placental immune cells on trophoblast function and pregnancy maintenance in the FIV-infected cat requires additional study.",2011 Jul 5,"['Scott, Veronica L', 'Shack, Leslie A', 'Eells, Jeffrey B', 'Ryan, Peter L', 'Donaldson, Janet R', 'Coats, Karen S']",Virol J,,,True
6224ce8bb65afbb10b08238d5ecde8991d7ab0e2,PMC,Toxin-Based Therapeutic Approaches,http://dx.doi.org/10.3390/toxins2112519,PMC3153180,22069564,CC BY,"Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin.",2010 Oct 28,"['Shapira, Assaf', 'Benhar, Itai']",Toxins (Basel),,,True
eaf46f27d9c28f8b3c818b0d7969d9188a7e9c11,PMC,RNA-Binding Domain in the Nucleocapsid Protein of Gill-Associated Nidovirus of Penaeid Shrimp,http://dx.doi.org/10.1371/journal.pone.0022156,PMC3153931,21857914,CC BY,"Gill-associated virus (GAV) infects Penaeus monodon shrimp and is the type species okavirus in the Roniviridae, the only invertebrate nidoviruses known currently. Electrophoretic mobility shift assays (EMSAs) using His(6)-tagged full-length and truncated proteins were employed to examine the nucleic acid binding properties of the GAV nucleocapsid (N) protein in vitro. The EMSAs showed full-length N protein to bind to all synthetic single-stranded (ss)RNAs tested independent of their sequence. The ssRNAs included (+) and (−) sense regions of the GAV genome as well as a (+) sense region of the M RNA segment of Mourilyan virus, a crustacean bunya-like virus. GAV N protein also bound to double-stranded (ds)RNAs prepared to GAV ORF1b gene regions and to bacteriophage M13 genomic ssDNA. EMSAs using the five N protein constructs with variable-length N-terminal and/or C-terminal truncations localized the RNA binding domain to a 50 amino acid (aa) N-terminal sequence spanning Met(11) to Arg(60). Similarly to other RNA binding proteins, the first 16 aa portion of this sequence was proline/arginine rich. To examine this domain in more detail, the 18 aa peptide (M(11)PVRRPLPPQPPRNARLI(29)) encompassing this sequence was synthesized and found to bind nucleic acids similarly to the full-length N protein in EMSAs. The data indicate a fundamental role for the GAV N protein proline/arginine-rich domain in nucleating genomic ssRNA to form nucleocapsids. Moreover, as the synthetic peptide formed higher-order complexes in the presence of RNA, the domain might also play some role in protein/protein interactions stabilizing the helical structure of GAV nucleocapsids.",2011 Aug 3,"['Soowannayan, Chumporn', 'Cowley, Jeff A.', 'Michalski, Wojtek P.', 'Walker, Peter J.']",PLoS One,,,True
0a0cbd4cb08c862deadcb5aaef22a27b770c0791,PMC,Real-world comparison of two molecular methods for detection of respiratory viruses,http://dx.doi.org/10.1186/1743-422X-8-332,PMC3154182,21714915,CC BY,"BACKGROUND: Molecular polymerase chain reaction (PCR) based assays are increasingly used to diagnose viral respiratory infections and conduct epidemiology studies. Molecular assays have generally been evaluated by comparing them to conventional direct fluorescent antibody (DFA) or viral culture techniques, with few published direct comparisons between molecular methods or between institutions. We sought to perform a real-world comparison of two molecular respiratory viral diagnostic methods between two experienced respiratory virus research laboratories. METHODS: We tested nasal and throat swab specimens obtained from 225 infants with respiratory illness for 11 common respiratory viruses using both a multiplex assay (Respiratory MultiCode-PLx Assay [RMA]) and individual real-time RT-PCR (RT-rtPCR). RESULTS: Both assays detected viruses in more than 70% of specimens, but there was discordance. The RMA assay detected significantly more human metapneumovirus (HMPV) and respiratory syncytial virus (RSV), while RT-rtPCR detected significantly more influenza A. We speculated that primer differences accounted for these discrepancies and redesigned the primers and probes for influenza A in the RMA assay, and for HMPV and RSV in the RT-rtPCR assay. The tests were then repeated and again compared. The new primers led to improved detection of HMPV and RSV by RT-rtPCR assay, but the RMA assay remained similar in terms of influenza detection. CONCLUSIONS: Given the absence of a gold standard, clinical and research laboratories should regularly correlate the results of molecular assays with other PCR based assays, other laboratories, and with standard virologic methods to ensure consistency and accuracy.",2011 Jun 29,"['Ali, S Asad', 'Gern, James E', 'Hartert, Tina V', 'Edwards, Kathryn M', 'Griffin, Marie R', 'Miller, E  Kathryn', 'Gebretsadik, Tebeb', 'Pappas, Tressa', 'Lee, Wai- ming', 'Williams, John V']",Virol J,,,True
ce7b8f00255cb989194bd19a730abd529c0d1f82,PMC,The Microbial Detection Array Combined with Random Phi29-Amplification Used as a Diagnostic Tool for Virus Detection in Clinical Samples,http://dx.doi.org/10.1371/journal.pone.0022631,PMC3154197,21853040,CC BY,"A common technique used for sensitive and specific diagnostic virus detection in clinical samples is PCR that can identify one or several viruses in one assay. However, a diagnostic microarray containing probes for all human pathogens could replace hundreds of individual PCR-reactions and remove the need for a clear clinical hypothesis regarding a suspected pathogen. We have established such a diagnostic platform for random amplification and subsequent microarray identification of viral pathogens in clinical samples. We show that Phi29 polymerase-amplification of a diverse set of clinical samples generates enough viral material for successful identification by the Microbial Detection Array, demonstrating the potential of the microarray technique for broad-spectrum pathogen detection. We conclude that this method detects both DNA and RNA virus, present in the same sample, as well as differentiates between different virus subtypes. We propose this assay for diagnostic analysis of viruses in clinical samples.",2011 Aug 10,"['Erlandsson, Lena', 'Rosenstierne, Maiken W.', 'McLoughlin, Kevin', 'Jaing, Crystal', 'Fomsgaard, Anders']",PLoS One,,,True
98948855a76926474a0ca576cf984b00053fcac3,PMC,B Cell Repertoire Analysis Identifies New Antigenic Domains on Glycoprotein B of Human Cytomegalovirus which Are Target of Neutralizing Antibodies,http://dx.doi.org/10.1371/journal.ppat.1002172,PMC3154849,21852946,CC BY,"Human cytomegalovirus (HCMV), a herpesvirus, is a ubiquitously distributed pathogen that causes severe disease in immunosuppressed patients and infected newborns. Efforts are underway to prepare effective subunit vaccines and therapies including antiviral antibodies. However, current vaccine efforts are hampered by the lack of information on protective immune responses against HCMV. Characterizing the B-cell response in healthy infected individuals could aid in the design of optimal vaccines and therapeutic antibodies. To address this problem, we determined, for the first time, the B-cell repertoire against glycoprotein B (gB) of HCMV in different healthy HCMV seropositive individuals in an unbiased fashion. HCMV gB represents a dominant viral antigenic determinant for induction of neutralizing antibodies during infection and is also a component in several experimental HCMV vaccines currently being tested in humans. Our findings have revealed that the vast majority (>90%) of gB-specific antibodies secreted from B-cell clones do not have virus neutralizing activity. Most neutralizing antibodies were found to bind to epitopes not located within the previously characterized antigenic domains (AD) of gB. To map the target structures of these neutralizing antibodies, we generated a 3D model of HCMV gB and used it to identify surface exposed protein domains. Two protein domains were found to be targeted by the majority of neutralizing antibodies. Domain I, located between amino acids (aa) 133–343 of gB and domain II, a discontinuous domain, built from residues 121–132 and 344–438. Analysis of a larger panel of human sera from HCMV seropositive individuals revealed positivity rates of >50% against domain I and >90% against domain II, respectively. In accordance with previous nomenclature the domains were designated AD-4 (Dom II) and AD-5 (Dom I), respectively. Collectively, these data will contribute to optimal vaccine design and development of antibodies effective in passive immunization.",2011 Aug 11,"['Pötzsch, Sonja', 'Spindler, Nadja', 'Wiegers, Anna-Katharina', 'Fisch, Tanja', 'Rücker, Pia', 'Sticht, Heinrich', 'Grieb, Nina', 'Baroti, Tina', 'Weisel, Florian', 'Stamminger, Thomas', 'Martin-Parras, Luis', 'Mach, Michael', 'Winkler, Thomas H.']",PLoS Pathog,,,True
27b920651fc5c0ed145e70d1ab314ca3efc70754,PMC,B Cell Repertoire Analysis Identifies New Antigenic Domains on Glycoprotein B of Human Cytomegalovirus which Are Target of Neutralizing Antibodies,http://dx.doi.org/10.1371/journal.ppat.1002172,PMC3154849,21852946,CC BY,"Human cytomegalovirus (HCMV), a herpesvirus, is a ubiquitously distributed pathogen that causes severe disease in immunosuppressed patients and infected newborns. Efforts are underway to prepare effective subunit vaccines and therapies including antiviral antibodies. However, current vaccine efforts are hampered by the lack of information on protective immune responses against HCMV. Characterizing the B-cell response in healthy infected individuals could aid in the design of optimal vaccines and therapeutic antibodies. To address this problem, we determined, for the first time, the B-cell repertoire against glycoprotein B (gB) of HCMV in different healthy HCMV seropositive individuals in an unbiased fashion. HCMV gB represents a dominant viral antigenic determinant for induction of neutralizing antibodies during infection and is also a component in several experimental HCMV vaccines currently being tested in humans. Our findings have revealed that the vast majority (>90%) of gB-specific antibodies secreted from B-cell clones do not have virus neutralizing activity. Most neutralizing antibodies were found to bind to epitopes not located within the previously characterized antigenic domains (AD) of gB. To map the target structures of these neutralizing antibodies, we generated a 3D model of HCMV gB and used it to identify surface exposed protein domains. Two protein domains were found to be targeted by the majority of neutralizing antibodies. Domain I, located between amino acids (aa) 133–343 of gB and domain II, a discontinuous domain, built from residues 121–132 and 344–438. Analysis of a larger panel of human sera from HCMV seropositive individuals revealed positivity rates of >50% against domain I and >90% against domain II, respectively. In accordance with previous nomenclature the domains were designated AD-4 (Dom II) and AD-5 (Dom I), respectively. Collectively, these data will contribute to optimal vaccine design and development of antibodies effective in passive immunization.",2011 Aug 11,"['Pötzsch, Sonja', 'Spindler, Nadja', 'Wiegers, Anna-Katharina', 'Fisch, Tanja', 'Rücker, Pia', 'Sticht, Heinrich', 'Grieb, Nina', 'Baroti, Tina', 'Weisel, Florian', 'Stamminger, Thomas', 'Martin-Parras, Luis', 'Mach, Michael', 'Winkler, Thomas H.']",PLoS Pathog,,,False
72f81539c6237420551180793d727062bdd043bd,PMC,Successful Control of Methicillin-Resistant Staphylococcus aureus in Endemic Neonatal Intensive Care Units—A 7-Year Campaign,http://dx.doi.org/10.1371/journal.pone.0023001,PMC3155524,21857979,CC BY,"BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is among the most important nosocomial pathogens in the intensive care unit (ICU) worldwide, including Taiwan. Since 1997, our neonatal ICUs (NICUs) had become endemic for MRSA. METHODOLOGY/PRINCIPAL FINDINGS: To control MRSA spread in our NICUs, we implemented a series of infection control measures stepwise, including reinforcement of hand hygiene since January 2000, augmentation of aseptic care over the insertion site of central venous catheter since July 2001, introduction of alcohol-based handrubs since April 2003, surveillance culture for MRSA and cohort care for the colonized patients between March 2003 and February 2004, and surveillance culture with subsequent decolonization of MRSA between August 2005 and July 2006. After implementation of these measures, MRSA healthcare-associated infection (HAI) density reduced by 92%, from 5.47 episodes per 1000 patient-days in 1999 to 0.45 episodes per 1000 patient-days in 2006; MRSA bloodstream infection reduced from 40 cases in 1999 to only one case in 2006. Compared to those obtained during the period of surveillance culture without decolonization, both rates of MRSA colonization (8.6% vs. 41%, p<0.001) and infection (1.1% vs. 12%, p<0.001) decreased significantly during the period of surveillance and decolonization. Molecular analysis of the clinical isolates during the study period showed that the endemic clone, which dominated between 1998 and 2005, almost disappeared in 2006, while the community clones increased significantly in 2006–2007. CONCLUSION/SIGNIFICANCE: Through infection control measures, MRSA HAIs can be successfully controlled, even in areas with high levels of endemic MRSA infections such as our NICUs.",2011 Aug 12,"['Huang, Yhu-Chering', 'Lien, Rey-In', 'Su, Lin-Hui', 'Chou, Yi-Hong', 'Lin, Tzou-Yien']",PLoS One,,,True
87dda3063b97a87338264b45ae16045e46cb237b,PMC,Inflammatory Cytokine Expression Is Associated with Chikungunya Virus Resolution and Symptom Severity,http://dx.doi.org/10.1371/journal.pntd.0001279,PMC3156690,21858242,CC BY,"The Chikungunya virus infection zones have now quickly spread from Africa to parts of Asia, North America and Europe. Originally thought to trigger a disease of only mild symptoms, recently Chikungunya virus caused large-scale fatalities and widespread economic loss that was linked to recent virus genetic mutation and evolution. Due to the paucity of information on Chikungunya immunological progression, we investigated the serum levels of 13 cytokines/chemokines during the acute phase of Chikungunya disease and 6- and 12-month post-infection follow-up from patients of the Italian outbreak. We found that CXCL9/MIG, CCL2/MCP-1, IL-6 and CXCL10/IP-10 were significantly raised in the acute phase compared to follow-up samples. Furthermore, IL-1β, TNF-α, Il-12, IL-10, IFN-γ and IL-5 had low initial acute phase levels that significantly increased at later time points. Analysis of symptom severity showed association with CXCL9/MIG, CXCL10/IP-10 and IgG levels. These data give insight into Chikungunya disease establishment and subsequent convalescence, which is imperative to the treatment and containment of this quickly evolving and frequently re-emerging disease.",2011 Aug 16,"['Kelvin, Alyson A.', 'Banner, David', 'Silvi, Giuliano', 'Moro, Maria Luisa', 'Spataro, Nadir', 'Gaibani, Paolo', 'Cavrini, Francesca', 'Pierro, Anna', 'Rossini, Giada', 'Cameron, Mark J.', 'Bermejo-Martin, Jesus F.', 'Paquette, Stéphane G.', 'Xu, Luoling', 'Danesh, Ali', 'Farooqui, Amber', 'Borghetto, Ilaria', 'Kelvin, David J.', 'Sambri, Vittorio', 'Rubino, Salvatore']",PLoS Negl Trop Dis,,,True
64bfeb561f0664d74a04ee30a24a48159261d4fd,PMC,The Failure of R (0),http://dx.doi.org/10.1155/2011/527610,PMC3157160,21860658,CC BY,"The basic reproductive ratio, R (0), is one of the fundamental concepts in mathematical biology. It is a threshold parameter, intended to quantify the spread of disease by estimating the average number of secondary infections in a wholly susceptible population, giving an indication of the invasion strength of an epidemic: if R (0) < 1, the disease dies out, whereas if R (0) > 1, the disease persists. R (0) has been widely used as a measure of disease strength to estimate the effectiveness of control measures and to form the backbone of disease-management policy. However, in almost every aspect that matters, R (0) is flawed. Diseases can persist with R (0) < 1, while diseases with R (0) > 1 can die out. We show that the same model of malaria gives many different values of R (0), depending on the method used, with the sole common property that they have a threshold at 1. We also survey estimated values of R (0) for a variety of diseases, and examine some of the alternatives that have been proposed. If R (0) is to be used, it must be accompanied by caveats about the method of calculation, underlying model assumptions and evidence that it is actually a threshold. Otherwise, the concept is meaningless.",2011 Aug 16,"['Li, Jing', 'Blakeley, Daniel', 'Smith?, Robert J.']",Comput Math Methods Med,,,True
f4c1afe385e9e31eb5678e15a3c280ba97326554,PMC,High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France,http://dx.doi.org/10.1371/journal.pone.0023514,PMC3157400,21858150,CC BY,"BACKGROUND: Influenza-like illness (ILI) may be caused by a variety of pathogens. Clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. The limited use of molecular tools underestimates the role of other common pathogens. OBJECTIVES: During the early weeks of the 2009–2010 flu pandemic, a clinical and virological survey was conducted in adult and paediatric patients with ILI referred to two French University hospitals in Paris and Tours. Aims were to investigate the different pathogens involved in ILI and describe the associated symptoms. METHODS: H1N1v pandemic influenza diagnosis was performed with real time RT-PCR assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19®. Clinical data were collected prospectively by physicians using a standard questionnaire. RESULTS: From week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples (16.5%) were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 (61.9%) were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus (62.6%), followed by parainfluenza viruses (24.2%) and adenovirus (5.3%). 70.6% of H1N1v cases were identified in patients under 40 years and none after 65 years. There was no difference between clinical symptoms observed in patients infected with H1N1v or with other pathogens. CONCLUSION: Our results highlight the high frequency of non-influenza viruses involved in ILI during the pre-epidemic period of a flu alert and the lack of specific clinical signs associated with influenza infections. Rapid diagnostic screening of a large panel of respiratory pathogens may be critical to define and survey the epidemic situation and to provide critical information for patient management.",2011 Aug 17,"['Schnepf, Nathalie', 'Resche-Rigon, Matthieu', 'Chaillon, Antoine', 'Scemla, Anne', 'Gras, Guillaume', 'Semoun, Oren', 'Taboulet, Pierre', 'Molina, Jean-Michel', 'Simon, François', 'Goudeau, Alain', 'LeGoff, Jérôme']",PLoS One,,,True
7ba2b38fdd8158bce40520cb0a93c1d2889f64f9,PMC,Identification of a Highly Conserved H1 Subtype-Specific Epitope with Diagnostic Potential in the Hemagglutinin Protein of Influenza A Virus,http://dx.doi.org/10.1371/journal.pone.0023374,PMC3158760,21886787,CC BY,"Subtype specificity of influenza A virus (IAV) is determined by its two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). For HA, 16 distinct subtypes (H1–H16) exist, while nine exist for NA. The epidemic strains of H1N1 IAV change frequently and cause annual seasonal epidemics as well as occasional pandemics, such as the notorious 1918 influenza pandemic. The recent introduction of pandemic A/H1N1 IAV (H1N1pdm virus) into humans re-emphasizes the public health concern about H1N1 IAV. Several studies have identified conserved epitopes within specific HA subtypes that can be used for diagnostics. However, immune specific epitopes in H1N1 IAV have not been completely assessed. In this study, linear epitopes on the H1N1pdm viral HA protein were identified by peptide scanning using libraries of overlapping peptides against convalescent sera from H1N1pdm patients. One epitope, P5 (aa 58–72) was found to be immunodominant in patients and to evoke high titer antibodies in mice. Multiple sequence alignments and in silico coverage analysis showed that this epitope is highly conserved in influenza H1 HA [with a coverage of 91.6% (9,860/10,767)] and almost completely absent in other subtypes [with a coverage of 3.3% (792/23,895)]. This previously unidentified linear epitope is located outside the five well-recognized antigenic sites in HA. A peptide ELISA method based on this epitope was developed and showed high correlation (χ(2) = 51.81, P<0.01, Pearson correlation coefficient R = 0.741) with a hemagglutination inhibition test. The highly conserved H1 subtype-specific immunodominant epitope may form the basis for developing novel assays for sero-diagnosis and active surveillance against H1N1 IAVs.",2011 Aug 19,"['Zhao, Rongmao', 'Cui, Shujuan', 'Guo, Li', 'Wu, Chao', 'Gonzalez, Richard', 'Paranhos-Baccalà, Gláucia', 'Vernet, Guy', 'Wang, Jianwei', 'Hung, Tao']",PLoS One,,,True
2fe52e4cee440e3ca69f615221a85064b0641e0c,PMC,Intensive care of the cancer patient: recent achievements and remaining challenges,http://dx.doi.org/10.1186/2110-5820-1-5,PMC3159899,21906331,CC BY,"A few decades have passed since intensive care unit (ICU) beds have been available for critically ill patients with cancer. Although the initial reports showed dismal prognosis, recent data suggest that an increased number of patients with solid and hematological malignancies benefit from intensive care support, with dramatically decreased mortality rates. Advances in the management of the underlying malignancies and support of organ dysfunctions have led to survival gains in patients with life-threatening complications from the malignancy itself, as well as infectious and toxic adverse effects related to the oncological treatments. In this review, we will appraise the prognostic factors and discuss the overall perspective related to the management of critically ill patients with cancer. The prognostic significance of certain factors has changed over time. For example, neutropenia or autologous bone marrow transplantation (BMT) have less adverse prognostic implications than two decades ago. Similarly, because hematologists and oncologists select patients for ICU admission based on the characteristics of the malignancy, the underlying malignancy rarely influences short-term survival after ICU admission. Since the recent data do not clearly support the benefit of ICU support to unselected critically ill allogeneic BMT recipients, more outcome research is needed in this subgroup. Because of the overall increased survival that has been reported in critically ill patients with cancer, we outline an easy-to-use and evidence-based ICU admission triage criteria that may help avoid depriving life support to patients with cancer who can benefit. Lastly, we propose a research agenda to address unanswered questions.",2011 Mar 23,"['Azoulay, Elie', 'Soares, Marcio', 'Darmon, Michael', 'Benoit, Dominique', 'Pastores, Stephen', 'Afessa, Bekele']",Ann Intensive Care,,,True
3775869c0c45f1f0c92eec1d68f9b10827d299f3,PMC,Chinese Herbal Formula Xiao Yao San for Treatment of Depression: A Systematic Review of Randomized Controlled Trials,http://dx.doi.org/10.1155/2012/931636,PMC3159992,21869903,CC BY,"Objectives. To assess the beneficial and adverse effects of Xiaoyaosan for depression. Search Strategy. Electronic databases were searched until December 2009. Inclusion Criteria. We included randomized clinical trials testing Xiaoyaosan against placebo, antidepressants, or combined with antidepressants against antidepressants alone. Data Extraction and Analyses. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards. Results. 26 randomized trials (involving 1837 patients) were included and the methodological quality was evaluated as generally low. The pooled results showed that Xiaoyaosan combined with antidepressants was more effective in comprehensive effect, the score of HAMD and the score of SDS compared with antidepressants alone. Xiaoyaosan was superior to antidepressants for the score of HAMD. However, Xiaoyaosan was not different from placebo for the score of SDS. There was no adverse effects reported in the trials from Xiaoyaosan. Conclusions. Xiaoyaosan appears to be effective on improving symptoms in patients with depression. However, due to poor methodological quality in the majority of included trials, the potential benefit from Xiaoyaosan need to be confirmed in rigorous trials and the design and reporting of trials should follow international standards.",2012 Aug 22,"['Zhang, Yuqing', 'Han, Mei', 'Liu, Zhijun', 'Wang, Jie', 'He, Qingyong', 'Liu, Jianping']",Evid Based Complement Alternat Med,,,True
cc5bd8ae2cac9621202c04c1ec25699f5b7c3a91,PMC,Preventing the next 'SARS' - European healthcare workers' attitudes towards monitoring their health for the surveillance of newly emerging infections: qualitative study,http://dx.doi.org/10.1186/1471-2458-11-541,PMC3160373,21740552,CC BY,"BACKGROUND: Hospitals are often the epicentres of newly circulating infections. Healthcare workers (HCWs) are at high risk of acquiring infectious diseases and may be among the first to contract emerging infections. This study aims to explore European HCWs' perceptions and attitudes towards monitoring their absence and symptom reports for surveillance of newly circulating infections. METHODS: A qualitative study with thematic analysis was conducted using focus group methodology. Forty-nine hospital-based HCWs from 12 hospitals were recruited to six focus groups; two each in England and Hungary and one each in Germany and Greece. RESULTS: HCWs perceived risk factors for occupationally acquired infectious diseases to be 1.) exposure to patients with undiagnosed infections 2.) break-down in infection control procedures 3.) immuno-naïvety and 4.) symptomatic colleagues. They were concerned that a lack of monitoring and guidelines for infectious HCWs posed a risk to staff and patients and felt employers failed to take a positive interest in their health. Staffing demands and loss of income were noted as pressures to attend work when unwell. In the UK, Hungary and Greece participants felt monitoring staff absence and the routine disclosure of symptoms could be appropriate provided the effectiveness and efficiency of such a system were demonstrable. In Germany, legislation, privacy and confidentiality were identified as barriers. All HCWs highlighted the need for knowledge and structural improvements for timelier recognition of emerging infections. These included increased suspicion and awareness among staff and standardised, homogenous absence reporting systems. CONCLUSIONS: Monitoring absence and infectious disease symptom reports among HCWs may be a feasible means of surveillance for emerging infections in some settings. A pre-requisite will be tackling the drivers for symptomatic HCWs to attend work.",2011 Jul 8,"['Aghaizu, Adamma', 'Elam, Gillian', 'Ncube, Fortune', 'Thomson, Gail', 'Szilágyi, Emese', 'Eckmanns, Tim', 'Poulakou, Garyphallia', 'Catchpole, Mike']",BMC Public Health,,,True
66e863b67f8ef14a8a953841b6ddf7a2cefaf696,PMC,Estimating Incidence Curves of Several Infections Using Symptom Surveillance Data,http://dx.doi.org/10.1371/journal.pone.0023380,PMC3160845,21887246,CC BY,"We introduce a method for estimating incidence curves of several co-circulating infectious pathogens, where each infection has its own probabilities of particular symptom profiles. Our deconvolution method utilizes weekly surveillance data on symptoms from a defined population as well as additional data on symptoms from a sample of virologically confirmed infectious episodes. We illustrate this method by numerical simulations and by using data from a survey conducted on the University of Michigan campus. Last, we describe the data needs to make such estimates accurate.",2011 Aug 24,"['Goldstein, Edward', 'Cowling, Benjamin J.', 'Aiello, Allison E.', 'Takahashi, Saki', 'King, Gary', 'Lu, Ying', 'Lipsitch, Marc']",PLoS One,,,True
5a5e5fb3101062ab42831dae0bf504fd3e3a41f1,PMC,Prediction of Peptide Reactivity with Human IVIg through a Knowledge-Based Approach,http://dx.doi.org/10.1371/journal.pone.0023616,PMC3160895,21887285,CC BY,"The prediction of antibody-protein (antigen) interactions is very difficult due to the huge variability that characterizes the structure of the antibodies. The region of the antigen bound to the antibodies is called epitope. Experimental data indicate that many antibodies react with a panel of distinct epitopes (positive reaction). The Challenge 1 of DREAM5 aims at understanding whether there exists rules for predicting the reactivity of a peptide/epitope, i.e., its capability to bind to human antibodies. DREAM 5 provided a training set of peptides with experimentally identified high and low reactivities to human antibodies. On the basis of this training set, the participants to the challenge were asked to develop a predictive model of reactivity. A test set was then provided to evaluate the performance of the model implemented so far. We developed a logistic regression model to predict the peptide reactivity, by facing the challenge as a machine learning problem. The initial features have been generated on the basis of the available knowledge and the information reported in the dataset. Our predictive model had the second best performance of the challenge. We also developed a method, based on a clustering approach, able to “in-silico” generate a list of positive and negative new peptide sequences, as requested by the DREAM5 “bonus round” additional challenge. The paper describes the developed model and its results in terms of reactivity prediction, and highlights some open issues concerning the propensity of a peptide to react with human antibodies.",2011 Aug 24,"['Barbarini, Nicola', 'Tiengo, Alessandra', 'Bellazzi, Riccardo']",PLoS One,,,True
9bbaed357d3aa8c39af2508fb1ca775f8708ec41,PMC,"Molecular Basis of NDM-1, a New Antibiotic Resistance Determinant",http://dx.doi.org/10.1371/journal.pone.0023606,PMC3161043,21887283,CC BY,"The New Delhi Metallo-β-lactamase (NDM-1) was first reported in 2009 in a Swedish patient. A recent study reported that Klebsiella pneumonia NDM-1 positive strain or Escherichia coli NDM-1 positive strain was highly resistant to all antibiotics tested except tigecycline and colistin. These can no longer be relied on to treat infections and therefore, NDM-1 now becomes potentially a major global health threat. In this study, we performed modeling studies to obtain its 3D structure and NDM-1/antibiotics complex. It revealed that the hydrolytic mechanisms are highly conserved. In addition, the detailed analysis indicates that the more flexible and hydrophobic loop1, together with the evolution of more positive-charged loop2 leads to NDM-1 positive strain more potent and extensive in antibiotics resistance compared with other MBLs. Furthermore, through biological experiments, we revealed the molecular basis for antibiotics catalysis of NDM-1 on the enzymatic level. We found that NDM-1 enzyme was highly potent to degrade carbapenem antibiotics, while mostly susceptible to tigecycline, which had the ability to slow down the hydrolysis velocity of meropenem by NDM-1. Meanwhile, the mutagenesis experiments, including D124A, C208A, K211A and K211E, which displayed down-regulation on meropenem catalysis, proved the accuracy of our model. At present, there are no effective antibiotics against NDM-1 positive pathogen. Our study will provide clues to investigate the molecular basis of extended antibiotics resistance of NDM-1 and then accelerate the search for new antibiotics against NDM-1 positive strain in clinical studies.",2011 Aug 24,"['Liang, Zhongjie', 'Li, Lianchun', 'Wang, Yuanyuan', 'Chen, Limin', 'Kong, Xiangqian', 'Hong, Yao', 'Lan, Lefu', 'Zheng, Mingyue', 'Guang-Yang, Cai', 'Liu, Hong', 'Shen, Xu', 'Luo, Cheng', 'Li, Keqin Kathy', 'Chen, Kaixian', 'Jiang, Hualiang']",PLoS One,,,True
c92d4b764634f984f72efccaa63b365bebc10616,PMC,Phage Displayed Peptides to Avian H5N1 Virus Distinguished the Virus from Other Viruses,http://dx.doi.org/10.1371/journal.pone.0023058,PMC3161733,21887228,CC BY,"The purpose of the current study was to identify potential ligands and develop a novel diagnostic test to highly pathogenic avian influenza A virus (HPAI), subtype H5N1 viruses using phage display technology. The H5N1 viruses were used as an immobilized target in a biopanning process using a 12-mer phage display random peptide library. After five rounds of panning, three phages expressing peptides HAWDPIPARDPF, AAWHLIVALAPN or ATSHLHVRLPSK had a specific binding activity to H5N1 viruses were isolated. Putative binding motifs to H5N1 viruses were identified by DNA sequencing. In terms of the minimum quantity of viruses, the phage-based ELISA was better than antiserum-based ELISA and a manual, semi-quantitative endpoint RT-PCR for detecting H5N1 viruses. More importantly, the selected phages bearing the specific peptides to H5N1 viruses were capable of differentiating this virus from other avian viruses in enzyme-linked immunosorbent assays.",2011 Aug 22,"['Wu, Dan', 'Li, Guangxing', 'Qin, Chengfeng', 'Ren, Xiaofeng']",PLoS One,,,True
d1f35ee252fdb019a824ad4778e8e220c27fc608,PMC,Inhibition of SARS Pseudovirus Cell Entry by Lactoferrin Binding to Heparan Sulfate Proteoglycans,http://dx.doi.org/10.1371/journal.pone.0023710,PMC3161750,21887302,CC BY,"It has been reported that lactoferrin (LF) participates in the host immune response against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) invasion by enhancing NK cell activity and stimulating neutrophil aggregation and adhesion. We further investigated the role of LF in the entry of SARS pseudovirus into HEK293E/ACE2-Myc cells. Our results reveal that LF inhibits SARS pseudovirus infection in a dose-dependent manner. Further analysis suggested that LF was able to block the binding of spike protein to host cells at 4°C, indicating that LF exerted its inhibitory function at the viral attachment stage. However, LF did not disrupt the interaction of spike protein with angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV. Previous studies have shown that LF colocalizes with the widely distributed cell-surface heparan sulfate proteoglycans (HSPGs). Our experiments have also confirmed this conclusion. Treatment of the cells with heparinase or exogenous heparin prevented binding of spike protein to host cells and inhibited SARS pseudovirus infection, demonstrating that HSPGs provide the binding sites for SARS-CoV invasion at the early attachment phase. Taken together, our results suggest that, in addition to ACE2, HSPGs are essential cell-surface molecules involved in SARS-CoV cell entry. LF may play a protective role in host defense against SARS-CoV infection through binding to HSPGs and blocking the preliminary interaction between SARS-CoV and host cells. Our findings may provide further understanding of SARS-CoV pathogenesis and aid in treatment of this deadly disease.",2011 Aug 22,"['Lang, Jianshe', 'Yang, Ning', 'Deng, Jiejie', 'Liu, Kangtai', 'Yang, Peng', 'Zhang, Guigen', 'Jiang, Chengyu']",PLoS One,,,True
8f26b1ab1d54522ce151927a8cb48cf52058961a,PMC,Identification of M.tuberculosis-Specific Th1 Cells Expressing CD69 Generated in vivo in Pleural Fluid Cells from Patients with Tuberculous Pleurisy,http://dx.doi.org/10.1371/journal.pone.0023700,PMC3161751,21887301,CC BY,"Th1 cell-mediated immune responses at the site of active infection are important to restrict the growth of M.tuberculosis (MTB) and for the spontaneous resolution of patients with tuberculous pleurisy (TBP). In the present study, we found that without any stimulation, CD4(+) T cells in pleural fluid cells (PFCs) from patients with TBP expressed significantly higher levels of CD69 than PBMCs from patients with tuberculosis (TB) or healthy donors. CD4(+)CD69(+) T cells expressed T-bet and IL-12Rβ2. After stimulation with MTB-specific antigens, CD4(+)CD69(+) T cells expressed significantly higher levels of IFN-γ, IL-2 and TNF-α than CD4(+)CD69(−) T cells, demonstrating that CD4(+)CD69(+) T cells were MTB-specific Th1 cells. In addition, CD4(+)CD69(+) T cells were mostly polyfunctional Th1 cells that simultaneously produced IFN-γ, IL-2, TNF-α and displayed an effector or effector memory phenotype (CD45RA(−)CCR7(−)CD62L(−)CD27(−)). Moreover, the percentages of CD4(+)CD69(+) T cells were significantly and positively correlated with polyfunctional T cells. Interestingly, sorted CD4(+)CD69(+) but not CD4(+)CD69(−) fractions by flow cytometry produced IFN-γ, IL-2 and TNF-α that were significantly regulated by CD4(+)CD25(+) Treg cells. Taken together, based on the expression of CD69, we found a direct quantitative and qualitative method to detect and evaluate the in vivo generated MTB-specific polyfunctional CD4(+) T cells in PFCs from patients with TBP. This method can be used for the potential diagnosis and enrichment or isolation of MTB-specific Th1 cells in the investigations.",2011 Aug 22,"['Li, Li', 'Qiao, Dan', 'Fu, Xiaoying', 'Lao, Suihua', 'Zhang, Xianlan', 'Wu, Changyou']",PLoS One,,,True
a03298211c385b7bd1d1ebdc98b1cc69efe7f54d,PMC,"Systematic Identification of Novel, Essential Host Genes Affecting Bromovirus RNA Replication",http://dx.doi.org/10.1371/journal.pone.0023988,PMC3161824,21915247,CC BY,"Positive-strand RNA virus replication involves viral proteins and cellular proteins at nearly every replication step. Brome mosaic virus (BMV) is a well-established model for dissecting virus-host interactions and is one of very few viruses whose RNA replication, gene expression and encapsidation have been reproduced in the yeast Saccharomyces cerevisiae. Previously, our laboratory identified ∼100 non-essential host genes whose loss inhibited or enhanced BMV replication at least 3-fold. However, our isolation of additional BMV-modulating host genes by classical genetics and other results underscore that genes essential for cell growth also contribute to BMV RNA replication at a frequency that may be greater than that of non-essential genes. To systematically identify novel, essential host genes affecting BMV RNA replication, we tested a collection of ∼900 yeast strains, each with a single essential gene promoter replaced by a doxycycline-repressible promoter, allowing repression of gene expression by adding doxycycline to the growth medium. Using this strain array of ∼81% of essential yeast genes, we identified 24 essential host genes whose depleted expression reproducibly inhibited or enhanced BMV RNA replication. Relevant host genes are involved in ribosome biosynthesis, cell cycle regulation and protein homeostasis, among other cellular processes. BMV 2a(Pol) levels were significantly increased in strains depleted for a heat shock protein (HSF1) or proteasome components (PRE1 and RPT6), suggesting these genes may affect BMV RNA replication by directly or indirectly modulating 2a(Pol) localization, post-translational modification or interacting partners. Investigating the diverse functions of these newly identified essential host genes should advance our understanding of BMV-host interactions and normal cellular pathways, and suggest new modes of virus control.",2011 Aug 22,"['Gancarz, Brandi L.', 'Hao, Linhui', 'He, Qiuling', 'Newton, Michael A.', 'Ahlquist, Paul']",PLoS One,,,True
d0acac75cb3d2c19abfe061a5b1530b1dbbc6922,PMC,Dominating Biological Networks,http://dx.doi.org/10.1371/journal.pone.0023016,PMC3162560,21887225,CC BY,"Proteins are essential macromolecules of life that carry out most cellular processes. Since proteins aggregate to perform function, and since protein-protein interaction (PPI) networks model these aggregations, one would expect to uncover new biology from PPI network topology. Hence, using PPI networks to predict protein function and role of protein pathways in disease has received attention. A debate remains open about whether network properties of “biologically central (BC)” genes (i.e., their protein products), such as those involved in aging, cancer, infectious diseases, or signaling and drug-targeted pathways, exhibit some topological centrality compared to the rest of the proteins in the human PPI network. To help resolve this debate, we design new network-based approaches and apply them to get new insight into biological function and disease. We hypothesize that BC genes have a topologically central (TC) role in the human PPI network. We propose two different concepts of topological centrality. We design a new centrality measure to capture complex wirings of proteins in the network that identifies as TC those proteins that reside in dense extended network neighborhoods. Also, we use the notion of domination and find dominating sets (DSs) in the PPI network, i.e., sets of proteins such that every protein is either in the DS or is a neighbor of the DS. Clearly, a DS has a TC role, as it enables efficient communication between different network parts. We find statistically significant enrichment in BC genes of TC nodes and outperform the existing methods indicating that genes involved in key biological processes occupy topologically complex and dense regions of the network and correspond to its “spine” that connects all other network parts and can thus pass cellular signals efficiently throughout the network. To our knowledge, this is the first study that explores domination in the context of PPI networks.",2011 Aug 26,"['Milenković, Tijana', 'Memišević, Vesna', 'Bonato, Anthony', 'Pržulj, Nataša']",PLoS One,,,True
804df67d9b05a58b34332c92efec930254f5ebe3,PMC,A review of bronchiolitis obliterans syndrome and therapeutic strategies,http://dx.doi.org/10.1186/1749-8090-6-92,PMC3162889,21767391,CC BY,"Lung transplantation is an important treatment option for patients with advanced lung disease. Survival rates for lung transplant recipients have improved; however, the major obstacle limiting better survival is bronchiolitis obliterans syndrome (BOS). In the last decade, survival after lung retransplantation has improved for transplant recipients with BOS. This manuscript reviews BOS along with the current therapeutic strategies, including recent outcomes for lung retransplantation.",2011 Jul 18,"Hayes, Don",J Cardiothorac Surg,,,True
f7417991beaa7bd0483f9dbdd549c12eeee26508,PMC,Poly(I:C) promotes TNFα/TNFR1-dependent oligodendrocyte death in mixed glial cultures,http://dx.doi.org/10.1186/1742-2094-8-89,PMC3162898,21812954,CC BY,"BACKGROUND: Activation of glial cells via toll-like receptors (TLRs) and other intracellular pathogen recognition receptors promotes the release of potentially toxic acute phase reactants such as TNFα and nitric oxide into the extracellular space. As such, prolonged glial activation, as is thought to occur during a persistent viral infection of the CNS, may contribute to both neurodegeneration and demyelination. However, the effects of virus-induced glial activation on oligodendrocytes are not fully understood. METHOD: To determine the effects of glial activation on oligodendrocyte viability we treated primary glial cultures isolated from neonatal rats or mice with the RNA viral mimic poly(I:C) and in some cases other TLR ligands. TLR3 expression was determined by western blot. Cytokine levels were measured by RT-PCR, ELISA, and intracellular cytokine staining. Oligodendrocyte precursor (preOL) viability was determined by Alamar blue assays and immunocytochemistry. RESULT: Stimulation of mixed glial cultures with poly(I:C) resulted in microglia activation, TNFα production and preOL toxicity. This toxic effect of poly(I:C) was indirect as it failed to affect preOL viability in pure cultures despite the fact that preOLs express TLR3. Poly(I:C)-induced loss of preOLs was abolished in TNFα or TNFR1 deficient mixed glial cultures, suggesting that TNFα/TNFR1 signaling is required for poly(I:C) toxicity. Furthermore, although both microglia and astrocytes express functional TLR3, only microglia produced TNFα in culture. Consistent with these findings, other TLR agonists similarly triggered TNFα production and preOL toxicity in mixed glial cultures. CONCLUSION: Activation of microglia by poly(I:C) promotes TNFα/TNFR1-dependent oligodendroglial cell death. These data indicate that during an ongoing viral infection of the CNS, microglial TNFα may be detrimental to oligodendrocytes.",2011 Aug 3,"['Steelman, Andrew J', 'Li, Jianrong']",J Neuroinflammation,,,True
f1301ca67dfb936ebc49c73777088997c3fc23a6,PMC,Neglected Disease – African Sleeping Sickness: Recent Synthetic and Modeling Advances,http://dx.doi.org/10.3797/scipharm.1012-08,PMC3163371,21886894,CC BY,"Human African Trypanosomiasis (HAT) also called sleeping sickness is caused by subspecies of the parasitic hemoflagellate Trypanosoma brucei that mostly occurs in sub-Saharan Africa. The current chemotherapy of the human trypanosomiases relies on only six drugs, five of which have been developed more than 30 years ago, have undesirable toxic side effects and most of them show drug-resistance. Though development of new anti-trypanosomal drugs seems to be a priority area research in this area has lagged far behind. The given review mainly focus upon the recent synthetic and computer based approaches made by various research groups for the development of newer anti-trypanosomal analogues which may have improved efficacy and oral bioavailability than the present ones. The given paper also attempts to investigate the relationship between the various physiochemical parameters and anti-trypanosomal activity that may be helpful in development of potent anti-trypanosomal agents against sleeping sickness.",2011 May 10 Jul-Sep,"['Paliwal, Sarvesh K.', 'Verma, Ankita Narayan', 'Paliwal, Shailendra']",Sci Pharm,,,True
12af3b3c07569926eb1ce96ebd4d5bffd05ce54a,PMC,Genetic Variation of the Human α-2-Heremans-Schmid Glycoprotein (AHSG) Gene Associated with the Risk of SARS-CoV Infection,http://dx.doi.org/10.1371/journal.pone.0023730,PMC3163911,21904596,CC BY,"Genetic background may play an important role in the process of SARS-CoV infection and SARS development. We found several proteins that could interact with the nucleocapsid protein of the SARS coronavirus (SARS-CoV). α-2-Heremans-Schmid Glycoprotein (AHSG), which is required for macrophage deactivation by endogenous cations, is associated with inflammatory regulation. Cytochrome P450 Family 3A (CYP4F3A) is an ω-oxidase that inactivates Leukotriene B4 (LTB4) in human neutrophils and the liver. We investigated the association between the polymorphisms of these two inflammation-associated genes and SARS development. The linkage disequilibrium (LD) maps of these two genes were built with Haploview using data on CHB+JPT (version 2) from the HapMap. A total of ten tag SNPs were selected and genotyped. In the Guangzhou cohort study, after adjusting for age and sex, two AHSG SNPs and one CYP4F3 SNP were found to be associated with SARS susceptibility: rs2248690 (adjusted odds ratio [AOR] 2.42; 95% confidence interval [CI] 1.30-4.51); rs4917 (AOR 1.84; 95% CI 1.02-3.34); and rs3794987 (AOR 2.01; 95% CI 1.10–3.68). To further validate the association, the ten tag SNPs were genotyped in the Beijing cohort. After adjusting for age and sex, only rs2248690 (AOR, 1.63; 95% CI, 1.30–2.04) was found to be associated with SARS susceptibility. The combined analysis of the two studies confirmed tag SNP rs2248690 in AHSG as a susceptibility variant (AOR 1.70; 95% CI 1.37–2.09). The statistical analysis of the rs2248690 genotype data among the patients and healthy controls in the HCW cohort, who were all similarly exposed to the SARS virus, also supported the findings. Further, the SNP rs2248690 affected the transcriptional activity of the AHSG promoter and thus regulated the AHSG serum level. Therefore, our study has demonstrated that the AA genotype of rs2268690, which leads to a higher AHSG serum concentration, was significantly associated with protection against SARS development.",2011 Aug 17,"['Zhu, Xiaohui', 'Wang, Yan', 'Zhang, Hongxing', 'Liu, Xuan', 'Chen, Ting', 'Yang, Ruifu', 'Shi, Yuling', 'Cao, Wuchun', 'Li, Ping', 'Ma, Qingjun', 'Zhai, Yun', 'He, Fuchu', 'Zhou, Gangqiao', 'Cao, Cheng']",PLoS One,,,True
a73d97226cb958a94cd359666b35e092452818b7,PMC,Chlamydia trachomatis Co-opts GBF1 and CERT to Acquire Host Sphingomyelin for Distinct Roles during Intracellular Development,http://dx.doi.org/10.1371/journal.ppat.1002198,PMC3164637,21909260,CC BY,"The obligate intracellular pathogen Chlamydia trachomatis replicates within a membrane-bound inclusion that acquires host sphingomyelin (SM), a process that is essential for replication as well as inclusion biogenesis. Previous studies demonstrate that SM is acquired by a Brefeldin A (BFA)-sensitive vesicular trafficking pathway, although paradoxically, this pathway is dispensable for bacterial replication. This finding suggests that other lipid transport mechanisms are involved in the acquisition of host SM. In this work, we interrogated the role of specific components of BFA-sensitive and BFA-insensitive lipid trafficking pathways to define their contribution in SM acquisition during infection. We found that C. trachomatis hijacks components of both vesicular and non-vesicular lipid trafficking pathways for SM acquisition but that the SM obtained from these separate pathways is being utilized by the pathogen in different ways. We show that C. trachomatis selectively co-opts only one of the three known BFA targets, GBF1, a regulator of Arf1-dependent vesicular trafficking within the early secretory pathway for vesicle-mediated SM acquisition. The Arf1/GBF1-dependent pathway of SM acquisition is essential for inclusion membrane growth and stability but is not required for bacterial replication. In contrast, we show that C. trachomatis co-opts CERT, a lipid transfer protein that is a key component in non-vesicular ER to trans-Golgi trafficking of ceramide (the precursor for SM), for C. trachomatis replication. We demonstrate that C. trachomatis recruits CERT, its ER binding partner, VAP-A, and SM synthases, SMS1 and SMS2, to the inclusion and propose that these proteins establish an on-site SM biosynthetic factory at or near the inclusion. We hypothesize that SM acquired by CERT-dependent transport of ceramide and subsequent conversion to SM is necessary for C. trachomatis replication whereas SM acquired by the GBF1-dependent pathway is essential for inclusion growth and stability. Our results reveal a novel mechanism by which an intracellular pathogen redirects SM biosynthesis to its replicative niche.",2011 Sep 1,"['Elwell, Cherilyn A.', 'Jiang, Shaobo', 'Kim, Jung Hwa', 'Lee, Albert', 'Wittmann, Torsten', 'Hanada, Kentaro', 'Melancon, Paul', 'Engel, Joanne N.']",PLoS Pathog,,,True
fbb13d5bcfe0597fc854533fa1637fd4c415bb5a,PMC,A Recombinant Avian Infectious Bronchitis Virus Expressing a Heterologous Spike Gene Belonging to the 4/91 Serotype,http://dx.doi.org/10.1371/journal.pone.0024352,PMC3166170,21912629,CC BY,"We have shown previously that replacement of the spike (S) gene of the apathogenic IBV strain Beau-R with that from the pathogenic strain of the same serotype, M41, resulted in an apathogenic virus, BeauR-M41(S), that conferred protection against challenge with M41 [1]. We have constructed a recombinant IBV, BeauR-4/91(S), with the genetic backbone of Beau-R but expressing the spike protein of the pathogenic IBV strain 4/91(UK), which belongs to a different serogroup as Beaudette or M41. Similar to our previous findings with BeauR-M41(S), clinical signs observations showed that the S gene of the pathogenic 4/91 virus did not confer pathogenicity to the rIBV BeauR-4/91(S). Furthermore, protection studies showed there was homologous protection; BeauR-4/91(S) conferred protection against challenge with wild type 4/91 virus as shown by the absence of clinical signs, IBV RNA assessed by qRT-PCR and the fact that no virus was isolated from tracheas removed from birds primarily infected with BeauR-4/91(S) and challenged with IBV 4/91(UK). A degree of heterologous protection against M41 challenge was observed, albeit at a lower level. Our results confirm and extend our previous findings and conclusions that swapping of the ectodomain of the S protein is a precise and effective way of generating genetically defined candidate IBV vaccines.",2011 Aug 30,"['Armesto, Maria', 'Evans, Sharon', 'Cavanagh, David', 'Abu-Median, Abu-Bakr', 'Keep, Sarah', 'Britton, Paul']",PLoS One,,,True
4409a3d523a0e35a95671bb6d947c39763bd0bb0,PMC,NoD: a Nucleolar localization sequence detector for eukaryotic and viral proteins,http://dx.doi.org/10.1186/1471-2105-12-317,PMC3166288,21812952,CC BY,"BACKGROUND: Nucleolar localization sequences (NoLSs) are short targeting sequences responsible for the localization of proteins to the nucleolus. Given the large number of proteins experimentally detected in the nucleolus and the central role of this subnuclear compartment in the cell, NoLSs are likely to be important regulatory elements controlling cellular traffic. Although many proteins have been reported to contain NoLSs, the systematic characterization of this group of targeting motifs has only recently been carried out. RESULTS: Here, we describe NoD, a web server and a command line program that predicts the presence of NoLSs in proteins. Using the web server, users can submit protein sequences through the NoD input form and are provided with a graphical output of the NoLS score as a function of protein position. While the web server is most convenient for making prediction for just a few proteins, the command line version of NoD can return predictions for complete proteomes. NoD is based on our recently described human-trained artificial neural network predictor. Through stringent independent testing of the predictor using available experimentally validated NoLS-containing eukaryotic and viral proteins, the NoD sensitivity and positive predictive value were estimated to be 71% and 79% respectively. CONCLUSIONS: NoD is the first tool to provide predictions of nucleolar localization sequences in diverse eukaryotes and viruses. NoD can be run interactively online at http://www.compbio.dundee.ac.uk/nod or downloaded to use locally.",2011 Aug 3,"['Scott, Michelle S', 'Troshin, Peter V', 'Barton, Geoffrey J']",BMC Bioinformatics,,,True
24d7fe6bbb9945f1536fef5b281d074fe69cfc6a,PMC,Avian Influenza Risk Perception and Preventive Behavior among Traditional Market Workers and Shoppers in Taiwan: Practical Implications for Prevention,http://dx.doi.org/10.1371/journal.pone.0024157,PMC3166308,21912667,CC BY,"BACKGROUND: Avian influenza (AI) can be highly pathogenic and fatal. Preventive behavior such as handwashing and wearing face masks has been recommended. However, little is known about what psychosocial factors might influence people's decision to adopt such preventive behavior. This study aims to explore risk perception and other factors associated with handwashing and wearing face masks to prevent AI. METHODOLOGY/PRINCIPAL FINDINGS: An interviewer-administered survey was conducted among 352 traditional market workers and shoppers in Taiwan between December 2009 and January 2010. Factors associated with the recommended AI preventive behavior (i.e., when in a traditional market, wearing a face mask and also washing hands after any contact with poultry) included: having correct knowledge about the fatality rate of AI (adjusted odds ratio [AOR] = 4.18), knowing of severe cases of AI (AOR = 2.13), being informed of local AI outbreaks (AOR = 2.24), living in northeastern Taiwan (AOR = 6.01), having a senior high-school education (AOR = 3.33), and having a university or higher education (AOR = 6.86). Gender interactive effect was also found among participants with a senior high-school education, with males being less likely to engage in the recommended AI preventive behavior than their female counterparts (AOR = 0.34). CONCLUSIONS/SIGNIFICANCE: Specific information concerning AI risk perception was associated with the recommended AI preventive behavior. In particular, having correct knowledge about the fatality rate of AI and being informed of severe cases and local outbreaks of AI were linked to increased AI preventive behavior. These findings underscore the importance of transparency in dealing with epidemic information. These results also have practical implications for prevention and policy-making to more effectively promote the recommended AI preventive behavior in the public.",2011 Sep 2,"['Kuo, Pei-Chun', 'Huang, Jiun-Hau', 'Liu, Ming-Der']",PLoS One,,,True
259ac67e44e833ea06564160ee399b76985f1145,PMC,Plasma proteomic profile of sulfur mustard exposed lung diseases patients using 2-dimensional gel electrophoresis,http://dx.doi.org/10.1186/1559-0275-8-2,PMC3167199,21906349,CC BY,"INTRODUCTION: Sulfur mustard ""bis (2-chlroethyl) sulphide"" (SM) is a chemical warfare agent that remains a threat to human health. The aim of this study was to identify protein expression signature or biomarkers that reflect chronic lung damages induced by SM exposure. METHODS: Prior to analysis, plasma was fractionated using ethanol precipitation. Using two dimensional SDS-PAGE; fractionated protein profiles of 20 healthy and 20 exposed patients with lung diseases were established. Selected protein spots were successfully identified with MALDI TOF MS/MS. RESULTS: The results show that α1 haptoglobin isoforms were detected in plasma of the all lung disease patients but none of the healthy controls. Amyloid A1 isoforms was also detected in plasma of the lung disease patients but none of the healthy controls. Moreover, low molecular weight proteins were enriched in ethanol supernatant compared to ethanol precipitate. CONCLUSION: Our present results and previous studies suggest that ongoing tissue remodeling is involved in SM exposed lung damage patients. These finding might improve patient care and suitable therapies.",2011 Jan 7,"['Mehrani, Hossein', 'Ghanei, Mostafa', 'Aslani, Jafar', 'Tabatabaei, Zahra']",Clin Proteomics,,,True
b5c6a1c48730f12db7c74e51ca05a54fb4a9d202,PMC,Population response to the risk of vector-borne diseases: lessons learned from socio-behavioural research during large-scale outbreaks,http://dx.doi.org/10.3134/ehtj.09.006,PMC3167643,22460287,CC BY,"Vector-borne infectious diseases, such as malaria, dengue, chikungunya, and West Nile fevers are increasingly identified as major global human health threats in developing and developed countries. The success or failure of vector control rests mainly on the nature and scale of the behavioural response of exposed populations. Large-scale adoption of recommended protective behaviour represents a critical challenge that cannot be addressed without a better understanding of how individuals perceive and react to the risk of infection. Recently, French overseas territories faced large-scale outbreaks: an epidemic of chikungunya fever in La Re′ union and Mayotte (2005–2006) and four successive outbreaks of dengue fever in one Caribbean island, Martinique (1995–2007). To assess how these populations perceived and responded to the risk, and how the nature and scale of protection affected their clinical status, socio-epidemiological surveys were conducted on each island during the outbreaks. These surveys address three crucial and interconnected questions relevant to the period after persons infected by the virus were identified: which factors shape the risk of acquiring disease? Which socio- demographic characteristics and living conditions induce a higher likelihood of infection? What is the impact of risk perception on protective behaviours adopted against mosquito bites? Grounded on the results of these surveys, a general framework is proposed to help draw out the knowledge needed to reveal the factors associated with higher probability of infection as an outbreak emerges. The lessons learnt can inform health authorities’ efforts to improve risk communication programmes, both in terms of the target and content of messages, so as to explore new strategies for ensuring sustainable protective behaviour. The authors compare three epidemics of vector-borne diseases to elucidate psychosocial factors that determine how populations perceive and respond to the risk of infectious disease.",2009 Jul 31,"['Setbon, M', 'Raude, J']",Emerg Health Threats J,,,True
b817c40ff2740be4fb203fbef15d27aa6e25c299,PMC,"Migrants and emerging public health issues in a globalized world: threats, risks and challenges, an evidence-based framework",http://dx.doi.org/10.3134/ehtj.09.010,PMC3167650,22460280,CC BY,"International population mobility is an underlying factor in the emergence of public health threats and risks that must be managed globally. These risks are often related, but not limited, to transmissible pathogens. Mobile populations can link zones of disease emergence to lowprevalence or nonendemic areas through rapid or high-volume international movements, or both. Against this background of human movement, other global processes such as economics, trade, transportation, environment and climate change, as well as civil security influence the health impacts of disease emergence. Concurrently, global information systems, together with regulatory frameworks for disease surveillance and reporting, affect organizational and public awareness of events of potential public health significance. International regulations directed at disease mitigation and control have not kept pace with the growing challenges associated with the volume, speed, diversity, and disparity of modern patterns of human movement. The thesis that human population mobility is itself a major determinant of global public health is supported in this article by review of the published literature from the perspective of determinants of health (such as genetics/biology, behavior, environment, and socioeconomics), population-based disease prevalence differences, existing national and international health policies and regulations, as well as inter-regional shifts in population demographics and health outcomes. This paper highlights some of the emerging threats and risks to public health, identifies gaps in existing frameworks to manage health issues associated with migration, and suggests changes in approach to population mobility, globalization, and public health. The proposed integrated approach includes a broad spectrum of stakeholders ranging from individual health-care providers to policy makers and international organizations that are primarily involved in global health management, or are influenced by global health events.",2010 Mar 31,"['Gushulak, BD', 'Weekers, J', 'MacPherson, DW']",Emerg Health Threats J,,,True
813d4108f75af14e71c3b9fdc9281c30ba90b39e,PMC,In the name of the greater good?,http://dx.doi.org/10.3134/ehtj.09.012,PMC3167651,22460282,CC BY,"In the event of a pandemic that poses widespread infection and high death rates, the utilitarian mandate to ‘reduce harm’ is the relevant moral value that trumps other ethical considerations. The primacy of a utilitarian approach dictates that those who are in a position to assist the cessation of the most serious outbreaks in whatever role they may have, must be present to provide their services, and those who administer health care must also be present to ensure that all responders are supported and protected to the highest degree.",2010 Mar 31,"Kirkwood, K",Emerg Health Threats J,,,True
d4d15fb77f993153439d9ebd90c649962ee398e9,PMC,Emerging viral threats in Gabon: health capacities and response to the risk of emerging zoonotic diseases in Central Africa,http://dx.doi.org/10.3134/ehtj.10.163,PMC3167654,22460397,CC BY,"Emerging infectious diseases (EID) are currently the major threat to public health worldwide and most EID events have involved zoonotic infectious agents. Central Africa in general and Gabon in particular are privileged areas for the emergence of zoonotic EIDs. Indeed, human incursions in Gabonese forests for exploitation purposes lead to intensified contacts between humans and wildlife thus generating an increased risk of emergence of zoonotic diseases. In Gabon, 51 endemic or potential endemic viral infectious diseases have been reported. Among them, 22 are of zoonotic origin and involve 12 families of viruses. The most notorious are dengue, yellow fever, ebola, marburg, Rift Valley fever and chikungunya viruses. Potential EID due to wildlife in Gabon are thereby plentiful and need to be inventoried. The Gabonese Public Health system covers geographically most of the country allowing a good access to sanitary information and efficient monitoring of emerging diseases. However, access to treatment and prevention is better in urban areas where medical structures are more developed and financial means are concentrated even though the population is equally distributed between urban and rural areas. In spite of this, Gabon could be a good field for investigating the emergence or re-emergence of zoonotic EID. Indeed Gabonese health research structures such as CIRMF, advantageously located, offer high quality researchers and facilities that study pathogens and wildlife ecology, aiming toward a better understanding of the contact and transmission mechanisms of new pathogens from wildlife to human, the emergence of zoonotic EID and the breaking of species barriers by pathogens.",2010 Jun 3,"['Bourgarel, M', 'Wauquier, N', 'Gonzalez, J-P']",Emerg Health Threats J,,,True
5d9de14dd116027eb2325fc91534d038f8eac88b,PMC,Innovation in observation: a vision for early outbreak detection,http://dx.doi.org/10.3134/ehtj.10.006,PMC3167656,22460396,CC BY,"The emergence of new infections and resurgence of old ones—health threats stemming from environmental contamination or purposeful acts of bioterrorism—call for a worldwide effort in improving early outbreak detection, with the goal of ameliorating current and future risks. In some cases, the problem of outbreak detection is logistically straightforward and mathematically easy: a single case of a disease of great concern can constitute an outbreak. However, for the vast majority of maladies, a simple analytical solution does not exist. Furthermore, each step in developing reliable, sensitive, effective surveillance systems demonstrates enormous complexities in the transmission, manifestation, detection, and control of emerging health threats. In this communication, we explore potential future innovations in early outbreak detection systems that can overcome the pitfalls of current surveillance. We believe that modern advances in assembling data, techniques for collating and processing information, and technology that enables integrated analysis will facilitate a new paradigm in outbreak definition and detection. We anticipate that moving forward in this direction will provide the highly desired sensitivity and specificity in early detection required to meet the emerging challenges of global disease surveillance.",2010 May 20,"['Fefferman, NH', 'Naumova, EN']",Emerg Health Threats J,,,True
c0789cc30e0766ccdea9e216da799f9cb41f853d,PMC,Human rhinovirus C: a newly discovered human rhinovirus species,http://dx.doi.org/10.3134/ehtj.10.002,PMC3167658,22460392,CC BY,"Although often ignored, human rhinoviruses (HRVs) are the most frequent causes of respiratory tract infections (RTIs). A group of closely related novel rhinoviruses have recently been discovered. Based on their unique phylogenetic position and distinct genomic features, they are classified as a separate species, HRV-C. After their discovery, HRV-C viruses have been detected in patients worldwide, with a reported prevalence of 1.4–30.9% among tested specimens. This suggests that the species contribute to a significant proportion of RTIs that were unrecognized in the past. HRV-C is also the predominant HRV species, often with a higher detection rate than that of the two previously known species, HRV-A and HRV-B. HRV-C infections appear to peak in fall or winter in most temperate or subtropical countries, but may predominate in the rainy season in the tropics. In children, HRV-C is often associated with upper RTIs, with asthma exacerbation and wheezing episodes being common complications. The virus has also been detected in children with bronchitis, bronchiolitis, pneumonia, otitis media, sinusitis and systemic infections complicated by pericarditis. As for adults, HRV-C has been associated with more severe disease such as pneumonia and exacerbation of chronic obstructive pulmonary disease. However, larger clinical studies with asymptomatic controls are required to better define the significance of HRV-C infection in the adult population. On the basis of VP4 sequence analysis, a potential distinct subgroup within HRV-C has also been identified, although more complete genome sequences are needed to better define the genetic diversity of HRV-C.",2010 Oct 4,"['LauLau, S K P, SK', 'YipYip, C C Y, CC', 'WooWoo, P C Y, PC', 'Yuen, K-Y']",Emerg Health Threats J,,,True
a6c379baf7fcba6a32b8fdadbcd9a85032dd4729,PMC,Synthetic long oligonucleotides to generate artificial templates for use as positive controls in molecular assays: drug resistance mutations in influenza virus as an example,http://dx.doi.org/10.1186/1743-422X-8-405,PMC3168426,21843374,CC BY,"BACKGROUND: Positive controls are an integral component of any sensitive molecular diagnostic tool, but this can be affected, if several mutations are being screened in a scenario of a pandemic or newly emerging disease where it can be difficult to acquire all the necessary positive controls from the host. This work describes the development of a synthetic oligo-cassette for positive controls for accurate and highly sensitive diagnosis of several mutations relevant to influenza virus drug resistance. RESULTS: Using influenza antiviral drug resistance mutations as an example by employing the utility of synthetic paired long oligonucleotides containing complementary sequences at their 3' ends and utilizing the formation of oligonucleotide dimers and DNA polymerization, we generated ~170bp dsDNA containing several known specific neuraminidase inhibitor (NAI) resistance mutations. These templates were further cloned and successfully applied as positive controls in downstream assays. CONCLUSION: This approach significantly improved the development of diagnosis of resistance mutations in terms of time, accuracy, efficiency and sensitivity, which are paramount to monitoring the emergence and spread of antiviral drug resistant influenza strains. Thus, this may have a significantly broader application in molecular diagnostics along with its application in rapid molecular testing of all relevant mutations in an event of pandemic.",2011 Aug 16,"['Wang, Bin', 'Steain, Megan C', 'Dwyer, Dominic E', 'Cunningham, Anthony L', 'Saksena, Nitin K']",Virol J,,,True
8bb9d8f7eeb8272924275f349e5c63a5bb006445,PMC,Annexin A2 Binds RNA and Reduces the Frameshifting Efficiency of Infectious Bronchitis Virus,http://dx.doi.org/10.1371/journal.pone.0024067,PMC3168876,21918681,CC BY,"Annexin A2 (ANXA2) is a protein implicated in diverse cellular functions, including exocytosis, DNA synthesis and cell proliferation. It was recently proposed to be involved in RNA metabolism because it was shown to associate with some cellular mRNA. Here, we identified ANXA2 as a RNA binding protein (RBP) that binds IBV (Infectious Bronchitis Virus) pseudoknot RNA. We first confirmed the binding of ANXA2 to IBV pseudoknot RNA by ultraviolet crosslinking and showed its binding to RNA pseudoknot with ANXA2 protein in vitro and in the cells. Since the RNA pseudoknot located in the frameshifting region of IBV was used as bait for cellular RBPs, we tested whether ANXA2 could regulate the frameshfting of IBV pseudoknot RNA by dual luciferase assay. Overexpression of ANXA2 significantly reduced the frameshifting efficiency from IBV pseudoknot RNA and knockdown of the protein strikingly increased the frameshifting efficiency. The results suggest that ANXA2 is a cellular RBP that can modulate the frameshifting efficiency of viral RNA, enabling it to act as an anti-viral cellular protein, and hinting at roles in RNA metabolism for other cellular mRNAs.",2011 Aug 30,"['Kwak, Hoyun', 'Park, Min Woo', 'Jeong, Sunjoo']",PLoS One,,,True
479ad8e93a163df14be1cfbba80b448394298b5c,PMC,Structural genomics of infectious disease drug targets: the SSGCID,http://dx.doi.org/10.1107/S1744309111029204,PMC3169389,21904037,CC BY,"The Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a consortium of researchers at Seattle BioMed, Emerald BioStructures, the University of Washington and Pacific Northwest National Laboratory that was established to apply structural genomics approaches to drug targets from infectious disease organisms. The SSGCID is currently funded over a five-year period by the National Institute of Allergy and Infectious Diseases (NIAID) to determine the three-dimensional structures of 400 proteins from a variety of Category A, B and C pathogens. Target selection engages the infectious disease research and drug-therapy communities to identify drug targets, essential enzymes, virulence factors and vaccine candidates of biomedical relevance to combat infectious diseases. The protein-expression systems, purified proteins, ligand screens and three-dimensional structures produced by SSGCID con­stitute a valuable resource for drug-discovery research, all of which is made freely available to the greater scientific community. This issue of Acta Crystallographica Section F, entirely devoted to the work of the SSGCID, covers the details of the high-throughput pipeline and presents a series of structures from a broad array of pathogenic organisms. Here, a background is provided on the structural genomics of infectious disease, the essential components of the SSGCID pipeline are discussed and a survey of progress to date is presented.",2011 Aug 13,"['Stacy, Robin', 'Begley, Darren W.', 'Phan, Isabelle', 'Staker, Bart L.', 'Van Voorhis, Wesley C.', 'Varani, Gabriele', 'Buchko, Garry W.', 'Stewart, Lance J.', 'Myler, Peter J.']",Acta Crystallogr Sect F Struct Biol Cryst Commun,,,False
89ac1ba1b647165fe0cf9cefd3dc65df8c162749,PMC,Glycyrrhizin as antiviral agent against Hepatitis C Virus,http://dx.doi.org/10.1186/1479-5876-9-112,PMC3169469,21762538,CC BY,"BACKGROUND: Hepatitis C virus is a major cause of chronic liver diseases which can lead to permanent liver damage, hepatocellular carcinoma and death. The presently available treatment with interferon plus ribavirin, has limited benefits due to adverse side effects such as anemia, depression, fatigue, and ""flu-like"" symptoms. Herbal plants have been used for centuries against different diseases including viral diseases and have become a major source of new compounds to treat bacterial and viral diseases. MATERIAL: The present study was design to study the antiviral effect of Glycyrrhizin (GL) against HCV. For this purpose, HCV infected liver cells were treated with GL at non toxic doses and HCV titer was measured by Quantitative real time RT-PCR. RESULTS AND DISCUSSION: Our results demonstrated that GL inhibit HCV titer in a dose dependent manner and resulted in 50% reduction of HCV at a concentration of 14 ± 2 μg. Comparative studies were made with interferon alpha to investigate synergistic effects, if any, between antiviral compound and interferon alpha 2a. Our data showed that GL exhibited synergistic effect when combined with interferon. Moreover, these results were verified by transiently transfecting the liver cells with HCV 3a core plasmid. The results proved that GL dose dependently inhibit the expression of HCV 3a core gene both at mRNA and protein levels while the GAPDH remained constant. CONCLUSION: Our results suggest that GL inhibit HCV full length viral particles and HCV core gene expression or function in a dose dependent manner and had synergistic effect with interferon. In future, GL along with interferon will be better option to treat HCV infection.",2011 Jul 18,"['Ashfaq, Usman A', 'Masoud, Muhammad S', 'Nawaz, Zafar', 'Riazuddin, Sheikh']",J Transl Med,,,True
a27cb38e8670f317f707a16661115a42b5b1b9fe,PMC,Proteome analysis of vaccinia virus IHD-W-infected HEK 293 cells with 2-dimensional gel electrophoresis and MALDI-PSD-TOF MS of on solid phase support N-terminally sulfonated peptides,http://dx.doi.org/10.1186/1743-422X-8-380,PMC3169512,21806805,CC BY,"BACKGROUND: Despite the successful eradication of smallpox by the WHO-led vaccination programme, pox virus infections remain a considerable health threat. The possible use of smallpox as a bioterrorism agent as well as the continuous occurrence of zoonotic pox virus infections document the relevance to deepen the understanding for virus host interactions. Since the permissiveness of pox infections is independent of hosts surface receptors, but correlates with the ability of the virus to infiltrate the antiviral host response, it directly depends on the hosts proteome set. In this report the proteome of HEK293 cells infected with Vaccinia Virus strain IHD-W was analyzed by 2-dimensional gel electrophoresis and MALDI-PSD-TOF MS in a bottom-up approach. RESULTS: The cellular and viral proteomes of VACV IHD-W infected HEK293 cells, UV-inactivated VACV IHD-W-treated as well as non-infected cells were compared. Derivatization of peptides with 4-sulfophenyl isothiocyanate (SPITC) carried out on ZipTipμ-C18 columns enabled protein identification via the peptides' primary sequence, providing improved s/n ratios as well as signal intensities of the PSD spectra. The expression of more than 24 human proteins was modulated by the viral infection. Effects of UV-inactivated and infectious viruses on the hosts' proteome concerning energy metabolism and proteins associated with gene expression and protein-biosynthesis were quite similar. These effects might therefore be attributed to virus entry and virion proteins. However, the modulation of proteins involved in apoptosis was clearly correlated to infectious viruses. CONCLUSIONS: The proteome analysis of infected cells provides insight into apoptosis modulation, regulation of cellular gene expression and the regulation of energy metabolism. The confidence of protein identifications was clearly improved by the peptides' derivatization with SPITC on a solid phase support. Some of the identified proteins have not been described in the context of poxvirus infections before and need to be further characterised to identify their meaning for apoptosis modulation and pathogenesis.",2011 Aug 1,"['Bartel, Sebastian', 'Doellinger, Joerg', 'Darsow, Kai', 'Bourquain, Daniel', 'Buchholz, Rainer', 'Nitsche, Andreas', 'Lange, Harald A']",Virol J,,,True
6b67761a8689f2744b4046161187a0d128a5d7d1,PMC,"Discovery of the First Insect Nidovirus, a Missing Evolutionary Link in the Emergence of the Largest RNA Virus Genomes",http://dx.doi.org/10.1371/journal.ppat.1002215,PMC3169540,21931546,CC BY,"Nidoviruses with large genomes (26.3–31.7 kb; ‘large nidoviruses’), including Coronaviridae and Roniviridae, are the most complex positive-sense single-stranded RNA (ssRNA+) viruses. Based on genome size, they are far separated from all other ssRNA+ viruses (below 19.6 kb), including the distantly related Arteriviridae (12.7–15.7 kb; ‘small nidoviruses’). Exceptionally for ssRNA+ viruses, large nidoviruses encode a 3′-5′exoribonuclease (ExoN) that was implicated in controlling RNA replication fidelity. Its acquisition may have given rise to the ancestor of large nidoviruses, a hypothesis for which we here provide evolutionary support using comparative genomics involving the newly discovered first insect-borne nidovirus. This Nam Dinh virus (NDiV), named after a Vietnamese province, was isolated from mosquitoes and is yet to be linked to any pathology. The genome of this enveloped 60–80 nm virus is 20,192 nt and has a nidovirus-like polycistronic organization including two large, partially overlapping open reading frames (ORF) 1a and 1b followed by several smaller 3′-proximal ORFs. Peptide sequencing assigned three virion proteins to ORFs 2a, 2b, and 3, which are expressed from two 3′-coterminal subgenomic RNAs. The NDiV ORF1a/ORF1b frameshifting signal and various replicative proteins were tentatively mapped to canonical positions in the nidovirus genome. They include six nidovirus-wide conserved replicase domains, as well as the ExoN and 2′-O-methyltransferase that are specific to large nidoviruses. NDiV ORF1b also encodes a putative N7-methyltransferase, identified in a subset of large nidoviruses, but not the uridylate-specific endonuclease that – in deviation from the current paradigm - is present exclusively in the currently known vertebrate nidoviruses. Rooted phylogenetic inference by Bayesian and Maximum Likelihood methods indicates that NDiV clusters with roniviruses and that its branch diverged from large nidoviruses early after they split from small nidoviruses. Together these characteristics identify NDiV as the prototype of a new nidovirus family and a missing link in the transition from small to large nidoviruses.",2011 Sep 8,"['Nga, Phan Thi', 'Parquet, Maria del Carmen', 'Lauber, Chris', 'Parida, Manmohan', 'Nabeshima, Takeshi', 'Yu, Fuxun', 'Thuy, Nguyen Thanh', 'Inoue, Shingo', 'Ito, Takashi', 'Okamoto, Kenta', 'Ichinose, Akitoyo', 'Snijder, Eric J.', 'Morita, Kouichi', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,True
5bff2f7964b21fc01b102c421814e9ef05b2f2a1,PMC,"Discovery of the First Insect Nidovirus, a Missing Evolutionary Link in the Emergence of the Largest RNA Virus Genomes",http://dx.doi.org/10.1371/journal.ppat.1002215,PMC3169540,21931546,CC BY,"Nidoviruses with large genomes (26.3–31.7 kb; ‘large nidoviruses’), including Coronaviridae and Roniviridae, are the most complex positive-sense single-stranded RNA (ssRNA+) viruses. Based on genome size, they are far separated from all other ssRNA+ viruses (below 19.6 kb), including the distantly related Arteriviridae (12.7–15.7 kb; ‘small nidoviruses’). Exceptionally for ssRNA+ viruses, large nidoviruses encode a 3′-5′exoribonuclease (ExoN) that was implicated in controlling RNA replication fidelity. Its acquisition may have given rise to the ancestor of large nidoviruses, a hypothesis for which we here provide evolutionary support using comparative genomics involving the newly discovered first insect-borne nidovirus. This Nam Dinh virus (NDiV), named after a Vietnamese province, was isolated from mosquitoes and is yet to be linked to any pathology. The genome of this enveloped 60–80 nm virus is 20,192 nt and has a nidovirus-like polycistronic organization including two large, partially overlapping open reading frames (ORF) 1a and 1b followed by several smaller 3′-proximal ORFs. Peptide sequencing assigned three virion proteins to ORFs 2a, 2b, and 3, which are expressed from two 3′-coterminal subgenomic RNAs. The NDiV ORF1a/ORF1b frameshifting signal and various replicative proteins were tentatively mapped to canonical positions in the nidovirus genome. They include six nidovirus-wide conserved replicase domains, as well as the ExoN and 2′-O-methyltransferase that are specific to large nidoviruses. NDiV ORF1b also encodes a putative N7-methyltransferase, identified in a subset of large nidoviruses, but not the uridylate-specific endonuclease that – in deviation from the current paradigm - is present exclusively in the currently known vertebrate nidoviruses. Rooted phylogenetic inference by Bayesian and Maximum Likelihood methods indicates that NDiV clusters with roniviruses and that its branch diverged from large nidoviruses early after they split from small nidoviruses. Together these characteristics identify NDiV as the prototype of a new nidovirus family and a missing link in the transition from small to large nidoviruses.",2011 Sep 8,"['Nga, Phan Thi', 'Parquet, Maria del Carmen', 'Lauber, Chris', 'Parida, Manmohan', 'Nabeshima, Takeshi', 'Yu, Fuxun', 'Thuy, Nguyen Thanh', 'Inoue, Shingo', 'Ito, Takashi', 'Okamoto, Kenta', 'Ichinose, Akitoyo', 'Snijder, Eric J.', 'Morita, Kouichi', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,False
05a0ef8d34e8f046dfb1d2b587fd8653cfab7018,PMC,"Discovery of the First Insect Nidovirus, a Missing Evolutionary Link in the Emergence of the Largest RNA Virus Genomes",http://dx.doi.org/10.1371/journal.ppat.1002215,PMC3169540,21931546,CC BY,"Nidoviruses with large genomes (26.3–31.7 kb; ‘large nidoviruses’), including Coronaviridae and Roniviridae, are the most complex positive-sense single-stranded RNA (ssRNA+) viruses. Based on genome size, they are far separated from all other ssRNA+ viruses (below 19.6 kb), including the distantly related Arteriviridae (12.7–15.7 kb; ‘small nidoviruses’). Exceptionally for ssRNA+ viruses, large nidoviruses encode a 3′-5′exoribonuclease (ExoN) that was implicated in controlling RNA replication fidelity. Its acquisition may have given rise to the ancestor of large nidoviruses, a hypothesis for which we here provide evolutionary support using comparative genomics involving the newly discovered first insect-borne nidovirus. This Nam Dinh virus (NDiV), named after a Vietnamese province, was isolated from mosquitoes and is yet to be linked to any pathology. The genome of this enveloped 60–80 nm virus is 20,192 nt and has a nidovirus-like polycistronic organization including two large, partially overlapping open reading frames (ORF) 1a and 1b followed by several smaller 3′-proximal ORFs. Peptide sequencing assigned three virion proteins to ORFs 2a, 2b, and 3, which are expressed from two 3′-coterminal subgenomic RNAs. The NDiV ORF1a/ORF1b frameshifting signal and various replicative proteins were tentatively mapped to canonical positions in the nidovirus genome. They include six nidovirus-wide conserved replicase domains, as well as the ExoN and 2′-O-methyltransferase that are specific to large nidoviruses. NDiV ORF1b also encodes a putative N7-methyltransferase, identified in a subset of large nidoviruses, but not the uridylate-specific endonuclease that – in deviation from the current paradigm - is present exclusively in the currently known vertebrate nidoviruses. Rooted phylogenetic inference by Bayesian and Maximum Likelihood methods indicates that NDiV clusters with roniviruses and that its branch diverged from large nidoviruses early after they split from small nidoviruses. Together these characteristics identify NDiV as the prototype of a new nidovirus family and a missing link in the transition from small to large nidoviruses.",2011 Sep 8,"['Nga, Phan Thi', 'Parquet, Maria del Carmen', 'Lauber, Chris', 'Parida, Manmohan', 'Nabeshima, Takeshi', 'Yu, Fuxun', 'Thuy, Nguyen Thanh', 'Inoue, Shingo', 'Ito, Takashi', 'Okamoto, Kenta', 'Ichinose, Akitoyo', 'Snijder, Eric J.', 'Morita, Kouichi', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,False
50a09303f9f740ea1b5f3eeaee66dd6bbd49d4f8,PMC,"Discovery of the First Insect Nidovirus, a Missing Evolutionary Link in the Emergence of the Largest RNA Virus Genomes",http://dx.doi.org/10.1371/journal.ppat.1002215,PMC3169540,21931546,CC BY,"Nidoviruses with large genomes (26.3–31.7 kb; ‘large nidoviruses’), including Coronaviridae and Roniviridae, are the most complex positive-sense single-stranded RNA (ssRNA+) viruses. Based on genome size, they are far separated from all other ssRNA+ viruses (below 19.6 kb), including the distantly related Arteriviridae (12.7–15.7 kb; ‘small nidoviruses’). Exceptionally for ssRNA+ viruses, large nidoviruses encode a 3′-5′exoribonuclease (ExoN) that was implicated in controlling RNA replication fidelity. Its acquisition may have given rise to the ancestor of large nidoviruses, a hypothesis for which we here provide evolutionary support using comparative genomics involving the newly discovered first insect-borne nidovirus. This Nam Dinh virus (NDiV), named after a Vietnamese province, was isolated from mosquitoes and is yet to be linked to any pathology. The genome of this enveloped 60–80 nm virus is 20,192 nt and has a nidovirus-like polycistronic organization including two large, partially overlapping open reading frames (ORF) 1a and 1b followed by several smaller 3′-proximal ORFs. Peptide sequencing assigned three virion proteins to ORFs 2a, 2b, and 3, which are expressed from two 3′-coterminal subgenomic RNAs. The NDiV ORF1a/ORF1b frameshifting signal and various replicative proteins were tentatively mapped to canonical positions in the nidovirus genome. They include six nidovirus-wide conserved replicase domains, as well as the ExoN and 2′-O-methyltransferase that are specific to large nidoviruses. NDiV ORF1b also encodes a putative N7-methyltransferase, identified in a subset of large nidoviruses, but not the uridylate-specific endonuclease that – in deviation from the current paradigm - is present exclusively in the currently known vertebrate nidoviruses. Rooted phylogenetic inference by Bayesian and Maximum Likelihood methods indicates that NDiV clusters with roniviruses and that its branch diverged from large nidoviruses early after they split from small nidoviruses. Together these characteristics identify NDiV as the prototype of a new nidovirus family and a missing link in the transition from small to large nidoviruses.",2011 Sep 8,"['Nga, Phan Thi', 'Parquet, Maria del Carmen', 'Lauber, Chris', 'Parida, Manmohan', 'Nabeshima, Takeshi', 'Yu, Fuxun', 'Thuy, Nguyen Thanh', 'Inoue, Shingo', 'Ito, Takashi', 'Okamoto, Kenta', 'Ichinose, Akitoyo', 'Snijder, Eric J.', 'Morita, Kouichi', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,False
7ad4571111757c52a7c4004a6cc1a9e3698a09f4,PMC,Vaccinia Virus Protein C6 Is a Virulence Factor that Binds TBK-1 Adaptor Proteins and Inhibits Activation of IRF3 and IRF7,http://dx.doi.org/10.1371/journal.ppat.1002247,PMC3169548,21931555,CC BY,"Recognition of viruses by pattern recognition receptors (PRRs) causes interferon-β (IFN-β) induction, a key event in the anti-viral innate immune response, and also a target of viral immune evasion. Here the vaccinia virus (VACV) protein C6 is identified as an inhibitor of PRR-induced IFN-β expression by a functional screen of select VACV open reading frames expressed individually in mammalian cells. C6 is a member of a family of Bcl-2-like poxvirus proteins, many of which have been shown to inhibit innate immune signalling pathways. PRRs activate both NF-κB and IFN regulatory factors (IRFs) to activate the IFN-β promoter induction. Data presented here show that C6 inhibits IRF3 activation and translocation into the nucleus, but does not inhibit NF-κB activation. C6 inhibits IRF3 and IRF7 activation downstream of the kinases TANK binding kinase 1 (TBK1) and IκB kinase-ε (IKKε), which phosphorylate and activate these IRFs. However, C6 does not inhibit TBK1- and IKKε-independent IRF7 activation or the induction of promoters by constitutively active forms of IRF3 or IRF7, indicating that C6 acts at the level of the TBK1/IKKε complex. Consistent with this notion, C6 immunoprecipitated with the TBK1 complex scaffold proteins TANK, SINTBAD and NAP1. C6 is expressed early during infection and is present in both nucleus and cytoplasm. Mutant viruses in which the C6L gene is deleted, or mutated so that the C6 protein is not expressed, replicated normally in cell culture but were attenuated in two in vivo models of infection compared to wild type and revertant controls. Thus C6 contributes to VACV virulence and might do so via the inhibition of PRR-induced activation of IRF3 and IRF7.",2011 Sep 8,"['Unterholzner, Leonie', 'Sumner, Rebecca P.', 'Baran, Marcin', 'Ren, Hongwei', 'Mansur, Daniel S.', 'Bourke, Nollaig M.', 'Randow, Felix', 'Smith, Geoffrey L.', 'Bowie, Andrew G.']",PLoS Pathog,,,True
fbf7143172cc18e911174a7ce32856a0a63afc1c,PMC,Self-reported adverse reactions in 4337 healthcare workers immunizations against novel H1N1 influenza,http://dx.doi.org/10.1186/1756-0500-4-297,PMC3170337,21849040,CC BY,"PURPOSE: The use of the 2009 H1N1 vaccine has generated much debate concerning safety issues among the general population and physicians. It was questioned if this is a safe vaccine. Therefore, we investigated the safety of an inactivated monovalent H1N1 pandemic influenza vaccine METHODS: We focused on the H1N1 pandemic influenza vaccine Pandemrix(® )and applied a self reporting questionnaire in a population of healthcare workers (HCWs) and medical students at a major university hospital. RESULTS: In total, 4337 individuals were vaccinated, consisting of 3808 HCWs and 529 medical students. The vaccination rate of the employees was higher than 40%. The majority of individuals were vaccinated in November 2009. In total, 291 of the 4337 vaccinations were reported to lead to one or more adverse reactions (6.7%). Local reactions were reported in 3.8%, myalgia and arthralgia in 3.7%, fatigue in 3.7%, headache in 3.1%. CONCLUSIONS: Our data together with available data from several national and international institutions points to a safe pandemic influenza vaccine.",2011 Aug 17,"['Bias, Harald', 'Quarcoo, David', 'Meier-Wronski, Claus', 'Wicker, Sabine', 'Seybold, Joachim', 'Nienhaus, Albert', 'Groneberg, David A', 'Roux, Andres de']",BMC Res Notes,,,True
8a45b8b7e677272ce3d5d750e943fe6584134a97,PMC,Intracellular Events and Cell Fate in Filovirus Infection,http://dx.doi.org/10.3390/v3081501,PMC3172725,21927676,CC BY,"Marburg and Ebola viruses cause a severe hemorrhagic disease in humans with high fatality rates. Early target cells of filoviruses are monocytes, macrophages, and dendritic cells. The infection spreads to the liver, spleen and later other organs by blood and lymph flow. A hallmark of filovirus infection is the depletion of non-infected lymphocytes; however, the molecular mechanisms leading to the observed bystander lymphocyte apoptosis are poorly understood. Also, there is limited knowledge about the fate of infected cells in filovirus disease. In this review we will explore what is known about the intracellular events leading to virus amplification and cell damage in filovirus infection. Furthermore, we will discuss how cellular dysfunction and cell death may correlate with disease pathogenesis.",2011 Aug 24,"['Olejnik, Judith', 'Ryabchikova, Elena', 'Corley, Ronald B.', 'Mühlberger, Elke']",Viruses,,,True
d7fa2195f292b4bd5cf3bce7670b11c254770923,PMC,Assessment of the Antiviral Properties of Recombinant Porcine SP-D against Various Influenza A Viruses In Vitro,http://dx.doi.org/10.1371/journal.pone.0025005,PMC3173486,21935489,CC BY,"The emergence of influenza viruses resistant to existing classes of antiviral drugs raises concern and there is a need for novel antiviral agents that could be used therapeutically or prophylacticaly. Surfactant protein D (SP-D) belongs to the family of C-type lectins which are important effector molecules of the innate immune system with activity against bacteria and viruses, including influenza viruses. In the present study we evaluated the potential of recombinant porcine SP-D as an antiviral agent against influenza A viruses (IAVs) in vitro. To determine the range of antiviral activity, thirty IAVs of the subtypes H1N1, H3N2 and H5N1 that originated from birds, pigs and humans were selected and tested for their sensitivity to recombinant SP-D. Using these viruses it was shown by hemagglutination inhibition assay, that recombinant porcine SP-D was more potent than recombinant human SP-D and that especially higher order oligomeric forms of SP-D had the strongest antiviral activity. Porcine SP-D was active against a broad range of IAV strains and neutralized a variety of H1N1 and H3N2 IAVs, including 2009 pandemic H1N1 viruses. Using tissue sections of ferret and human trachea, we demonstrated that recombinant porcine SP-D prevented attachment of human seasonal H1N1 and H3N2 virus to receptors on epithelial cells of the upper respiratory tract. It was concluded that recombinant porcine SP-D holds promise as a novel antiviral agent against influenza and further development and evaluation in vivo seems warranted.",2011 Sep 14,"['Hillaire, Marine L. B.', 'van Eijk, Martin', 'van Trierum, Stella E.', 'van Riel, Debby', 'Saelens, Xavier', 'Romijn, Roland A.', 'Hemrika, Wieger', 'Fouchier, Ron A. M.', 'Kuiken, Thijs', 'Osterhaus, Albert D. M. E.', 'Haagsman, Henk P.', 'Rimmelzwaan, Guus F.']",PLoS One,,,True
25615501bc9f54fd01b72047cec1f8ec619b1e69,PMC,Unpolarized Release of Vaccinia Virus and HIV Antigen by Colchicine Treatment Enhances Intranasal HIV Antigen Expression and Mucosal Humoral Responses,http://dx.doi.org/10.1371/journal.pone.0024296,PMC3174162,21935396,CC BY,"The induction of a strong mucosal immune response is essential to building successful HIV vaccines. Highly attenuated recombinant HIV vaccinia virus can be administered mucosally, but even high doses of immunization have been found unable to induce strong mucosal antibody responses. In order to solve this problem, we studied the interactions of recombinant HIV vaccinia virus Tiantan strain (rVTT-gagpol) in mucosal epithelial cells (specifically Caco-2 cell layers) and in BALB/c mice. We evaluated the impact of this virus on HIV antigen delivery and specific immune responses. The results demonstrated that rVTT-gagpol was able to infect Caco-2 cell layers and both the nasal and lung epithelia in BALB/c mice. The progeny viruses and expressed p24 were released mainly from apical surfaces. In BALB/c mice, the infection was limited to the respiratory system and was not observed in the blood. This showed that polarized distribution limited antigen delivery into the whole body and thus limited immune response. To see if this could be improved upon, we stimulated unpolarized budding of the virus and HIV antigens by treating both Caco-2 cells and BALB/c mice with colchicine. We found that, in BALB/c mice, the degree of infection and antigen expression in the epithelia went up. As a result, specific immune responses increased correspondingly. Together, these data suggest that polarized budding limits antigen delivery and immune responses, but unpolarized distribution can increase antigen expression and delivery and thus enhance specific immune responses. This conclusion can be used to optimize mucosal HIV vaccine strategies.",2011 Sep 15,"['Zhang, Yan', 'Yang, Jingyi', 'Bao, Rong', 'Chen, Yaoqing', 'Zhou, Dihan', 'He, Benxia', 'Zhong, Maohua', 'Li, Yaoming', 'Liu, Fang', 'Li, Qiaoli', 'Yang, Yi', 'Han, Chen', 'Sun, Ying', 'Cao, Yuan', 'Yan, Huimin']",PLoS One,,,True
690ab99a21dca381b585a6a7d32f1e5c01f1e52c,PMC,Recurrent Recruitment Manoeuvres Improve Lung Mechanics and Minimize Lung Injury during Mechanical Ventilation of Healthy Mice,http://dx.doi.org/10.1371/journal.pone.0024527,PMC3174196,21935418,CC BY,"INTRODUCTION: Mechanical ventilation (MV) of mice is increasingly required in experimental studies, but the conditions that allow stable ventilation of mice over several hours have not yet been fully defined. In addition, most previous studies documented vital parameters and lung mechanics only incompletely. The aim of the present study was to establish experimental conditions that keep these parameters within their physiological range over a period of 6 h. For this purpose, we also examined the effects of frequent short recruitment manoeuvres (RM) in healthy mice. METHODS: Mice were ventilated at low tidal volume V(T) = 8 mL/kg or high tidal volume V(T) = 16 mL/kg and a positive end-expiratory pressure (PEEP) of 2 or 6 cmH(2)O. RM were performed every 5 min, 60 min or not at all. Lung mechanics were followed by the forced oscillation technique. Blood pressure (BP), electrocardiogram (ECG), heart frequency (HF), oxygen saturation and body temperature were monitored. Blood gases, neutrophil-recruitment, microvascular permeability and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) and blood serum as well as histopathology of the lung were examined. RESULTS: MV with repetitive RM every 5 min resulted in stable respiratory mechanics. Ventilation without RM worsened lung mechanics due to alveolar collapse, leading to impaired gas exchange. HF and BP were affected by anaesthesia, but not by ventilation. Microvascular permeability was highest in atelectatic lungs, whereas neutrophil-recruitment and structural changes were strongest in lungs ventilated with high tidal volume. The cytokines IL-6 and KC, but neither TNF nor IP-10, were elevated in the BAL and serum of all ventilated mice and were reduced by recurrent RM. Lung mechanics, oxygenation and pulmonary inflammation were improved by increased PEEP. CONCLUSIONS: Recurrent RM maintain lung mechanics in their physiological range during low tidal volume ventilation of healthy mice by preventing atelectasis and reduce the development of pulmonary inflammation.",2011 Sep 15,"['Reiss, Lucy Kathleen', 'Kowallik, Anke', 'Uhlig, Stefan']",PLoS One,,,True
54b6c7145a0f7743409d5590780ef253152873dd,PMC,Virtual High-Throughput Screening Identifies Mycophenolic Acid as a Novel RNA Capping Inhibitor,http://dx.doi.org/10.1371/journal.pone.0024806,PMC3174198,21935470,CC BY,"The RNA guanylyltransferase (GTase) is involved in the synthesis of the (m7)Gppp-RNA cap structure found at the 5′ end of eukaryotic mRNAs. GTases are members of the covalent nucleotidyl transferase superfamily, which also includes DNA and RNA ligases. GTases catalyze a two-step reaction in which they initially utilize GTP as a substrate to form a covalent enzyme-GMP intermediate. The GMP moiety is then transferred to the diphosphate end of the RNA transcript in the second step of the reaction to form the Gppp-RNA structure. In the current study, we used a combination of virtual database screening, homology modeling, and biochemical assays to search for novel GTase inhibitors. Using this approach, we demonstrate that mycophenolic acid (MPA) can inhibit the GTase reaction by preventing the catalytic transfer of the GMP moiety onto an acceptor RNA. As such, MPA represents a novel type of inhibitor against RNA guanylyltransferases that inhibits the second step of the catalytic reaction. Moreover, we show that the addition of MPA to S. cerevisiae cells leads to a reduction of capped mRNAs. Finally, biochemical assays also demonstrate that MPA can inhibit DNA ligases through inhibition of the second step of the reaction. The biological implications of these findings for the MPA-mediated inhibition of members of the covalent nucleotidyl superfamily are discussed.",2011 Sep 15,"['Tremblay-Létourneau, Maude', 'Despins, Simon', 'Bougie, Isabelle', 'Bisaillon, Martin']",PLoS One,,,True
3c3f097f19bb3dbbf56eb0f099af81054b305752,PMC,Distinguishing Characteristics between Pandemic 2009–2010 Influenza A (H1N1) and Other Viruses in Patients Hospitalized with Respiratory Illness,http://dx.doi.org/10.1371/journal.pone.0024734,PMC3174965,21949746,CC BY,"BACKGROUND: Differences in clinical presentation and outcomes among patients infected with pandemic 2009 influenza A H1N1 (pH1N1) compared to other respiratory viruses have not been fully elucidated. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective study was performed of all hospitalized patients at the peak of the pH1N1 season in whom a single respiratory virus was detected by a molecular assay targeting 18 viruses/subtypes (RVP, Luminex xTAG). Fifty-two percent (615/1192) of patients from October, 2009 to December, 2009 had a single respiratory virus (291 pH1N1; 207 rhinovirus; 45 RSV A/B; 37 parainfluenza; 27 adenovirus; 6 coronavirus; and 2 metapneumovirus). No seasonal influenza A or B was detected. Individuals with pH1N1, compared to other viruses, were more likely to present with fever (92% & 70%), cough (92% & 86%), sore throat (32% & 16%), nausea (31% & 8%), vomiting (39% & 30%), abdominal pain (14% & 7%), and a lower white blood count (8,500/L & 13,600/L, all p-values<0.05). In patients with cough and gastrointestinal complaints, the presence of subjective fever/chills independently raised the likelihood of pH1N1 (OR 10). Fifty-five percent (336/615) of our cohort received antibacterial agents, 63% (385/615) received oseltamivir, and 41% (252/615) received steroids. The mortality rate of our cohort was 1% (7/615) and was higher in individuals with pH1N1 compared to other viruses (2.1% & 0.3%, respectively; p = 0.04). CONCLUSIONS/SIGNIFICANCE: During the peak pandemic 2009–2010 influenza season in Rhode Island, nearly half of patients admitted with influenza-like symptoms had respiratory viruses other than influenza A. A high proportion of patients were treated with antibiotics and pH1N1 infection had higher mortality compared to other respiratory viruses.",2011 Sep 16,"['Chan, Philip A.', 'Mermel, Leonard A.', 'Andrea, Sarah B.', 'McCulloh, Russell', 'Mills, John P.', 'Echenique, Ignacio', 'Leveen, Emily', 'Rybak, Natasha', 'Cunha, Cheston', 'Machan, Jason T.', 'Healey, Terrance T.', 'Chapin, Kimberle C.']",PLoS One,,,True
28b906cb5b5dd66df68bdd155ccc2ab514180c2a,PMC,Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza,http://dx.doi.org/10.1186/1471-2334-11-232,PMC3175217,21880131,CC BY,"BACKGROUND: Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients. METHODS: Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient. RESULTS: Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-γ, the chemotactic factors MIP-1β, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra (p < 0.05). Correlation studies demonstrated also the existence of a significant positive association between the levels of these mediators, evidencing that they are simultaneously regulated in response to the virus. CONCLUSIONS: Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1.",2011 Aug 31,"['Almansa, Raquel', 'Anton, Andres', 'Ramirez, Paula', 'Martin-Loeches, Ignacio', 'Banner, David', 'Pumarola, Tomás', 'Xu, Luoling', 'Blanco, Jesús', 'Ran, Longsi', 'Lopez-Campos, Guillermo', 'Martin-Sanchez, Fernando', 'Socias, Lorenzo', 'Loza, Ana', 'Andaluz, David', 'Maravi, Enrique', 'Gordón, Mónica', 'Gallegos, Maria C', 'Fernandez, Victoria', 'León, Cristobal', 'Merino, Pedro', 'Marcos, Maria Ángeles', 'Gandía, Francisco', 'Bobillo, Felipe', 'Resino, Salvador', 'Eiros, Jose Mª', 'Castro, Carmen', 'Mateo, Paula', 'Gonzalez-Rivera, Milagros', 'Rello, Jordi', 'de Lejarazu, Raul Ortiz', 'Kelvin, David J', 'Bermejo-Martin, Jesus F']",BMC Infect Dis,,,True
0c82e4a717a9242e0462b24a8759f98f0c83d677,PMC,Discovery of DNA Viruses in Wild-Caught Mosquitoes Using Small RNA High throughput Sequencing,http://dx.doi.org/10.1371/journal.pone.0024758,PMC3176773,21949749,CC BY,"BACKGROUND: Mosquito-borne infectious diseases pose a severe threat to public health in many areas of the world. Current methods for pathogen detection and surveillance are usually dependent on prior knowledge of the etiologic agents involved. Hence, efficient approaches are required for screening wild mosquito populations to detect known and unknown pathogens. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we explored the use of Next Generation Sequencing to identify viral agents in wild-caught mosquitoes. We extracted total RNA from different mosquito species from South China. Small 18–30 bp length RNA molecules were purified, reverse-transcribed into cDNA and sequenced using Illumina GAIIx instrumentation. Bioinformatic analyses to identify putative viral agents were conducted and the results confirmed by PCR. We identified a non-enveloped single-stranded DNA densovirus in the wild-caught Culex pipiens molestus mosquitoes. The majority of the viral transcripts (.>80% of the region) were covered by the small viral RNAs, with a few peaks of very high coverage obtained. The +/− strand sequence ratio of the small RNAs was approximately 7∶1, indicating that the molecules were mainly derived from the viral RNA transcripts. The small viral RNAs overlapped, enabling contig assembly of the viral genome sequence. We identified some small RNAs in the reverse repeat regions of the viral 5′- and 3′ -untranslated regions where no transcripts were expected. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate for the first time that high throughput sequencing of small RNA is feasible for identifying viral agents in wild-caught mosquitoes. Our results show that it is possible to detect DNA viruses by sequencing the small RNAs obtained from insects, although the underlying mechanism of small viral RNA biogenesis is unclear. Our data and those of other researchers show that high throughput small RNA sequencing can be used for pathogen surveillance in wild mosquito vectors.",2011 Sep 20,"['Ma, Maijuan', 'Huang, Yong', 'Gong, Zhengda', 'Zhuang, Lu', 'Li, Cun', 'Yang, Hong', 'Tong, Yigang', 'Liu, Wei', 'Cao, Wuchun']",PLoS One,,,True
dad72f4c1b14ead806c29f48ce276b06ffeb421a,PMC,Distribution of sialic acid receptors and influenza A virus of avian and swine origin in experimentally infected pigs,http://dx.doi.org/10.1186/1743-422X-8-434,PMC3177912,21902821,CC BY,"BACKGROUND: Pigs are considered susceptible to influenza A virus infections from different host origins because earlier studies have shown that they have receptors for both avian (sialic acid-alpha-2,3-terminal saccharides (SA-alpha-2,3)) and swine/human (SA-alpha-2,6) influenza viruses in the upper respiratory tract. Furthermore, experimental and natural infections in pigs have been reported with influenza A virus from avian and human sources. METHODS: This study investigated the receptor distribution in the entire respiratory tract of pigs using specific lectins Maackia Amurensis (MAA) I, and II, and Sambucus Nigra (SNA). Furthermore, the predilection sites of swine influenza virus (SIV) subtypes H1N1 and H1N2 as well as avian influenza virus (AIV) subtype H4N6 were investigated in the respiratory tract of experimentally infected pigs using immunohistochemical methods. RESULTS: SIV antigen was widely distributed in bronchi, but was also present in epithelial cells of the nose, trachea, bronchioles, and alveolar type I and II epithelial cells in severely affected animals. AIV was found in the lower respiratory tract, especially in alveolar type II epithelial cells and occasionally in bronchiolar epithelial cells. SA-alpha-2,6 was the predominant receptor in all areas of the respiratory tract with an average of 80-100% lining at the epithelial cells. On the contrary, the SA-alpha-2,3 was not present (0%) at epithelial cells of nose, trachea, and most bronchi, but was found in small amounts in bronchioles, and in alveoli reaching an average of 20-40% at the epithelial cells. Interestingly, the receptor expression of both SA-alpha-2,3 and 2,6 was markedly diminished in influenza infected areas compared to non-infected areas. CONCLUSIONS: A difference in predilection sites between SIV and AIV virus was found, and this difference was in accordance with the distribution of the SA-alpha-2,6 and SA-alpha-2,3 receptor, respectively. The results indicated that the distribution of influenza A virus receptors in pigs are similar to that of humans and therefore challenge the theory that the pig acts as a mixing vessel between human and avian influenza viruses. Furthermore, it was shown that AIV prefers to infect alveolar type II epithelial cells in pigs. This corresponds with findings in humans emphasising the resemblance between the two species.",2011 Sep 8,"['Trebbien, Ramona', 'Larsen, Lars E', 'Viuff, Birgitte M']",Virol J,,,True
52659b7eb39ce3c761658f1f3e5df475cf495919,PMC,Changes in Cytokine Levels and NK Cell Activation Associated with Influenza,http://dx.doi.org/10.1371/journal.pone.0025060,PMC3179484,21966414,CC BY,"Several studies have highlighted the important role played by murine natural killer (NK) cells in the control of influenza infection. However, human NK cell responses in acute influenza infection, including infection with the 2009 pandemic H1N1 influenza virus, are poorly documented. Here, we examined changes in NK cell phenotype and function and plasma cytokine levels associated with influenza infection and vaccination. We show that absolute numbers of peripheral blood NK cells, and particularly those of CD56(bright) NK cells, decreased upon acute influenza infection while this NK cell subset expanded following intramuscular influenza vaccination. NK cells exposed to influenza antigens were activated, with higher proportions of NK cells expressing CD69 in study subjects infected with seasonal influenza strains. Vaccination led to increased levels of CD25+ NK cells, and notably CD56(bright) CD25+ NK cells, whereas decreased amounts of this subset were present in the peripheral blood of influenza infected individuals, and predominantly in study subjects infected with the 2009 pandemic H1N1 influenza virus. Finally, acute influenza infection was associated with low plasma concentrations of inflammatory cytokines, including IFN-γ, MIP-1β, IL-2 and IL-15, and high levels of the anti-inflammatory cytokines IL-10 and IL-1ra. Altogether, these data suggest a role for the CD56(bright) NK cell subset in the response to influenza, potentially involving their recruitment to infected tissues and a local production and/or uptake of inflammatory cytokines.",2011 Sep 23,"['Jost, Stephanie', 'Quillay, Heloise', 'Reardon, Jeff', 'Peterson, Eric', 'Simmons, Rachel P.', 'Parry, Blair A.', 'Bryant, Nancy N. P.', 'Binder, William D.', 'Altfeld, Marcus']",PLoS One,,,True
2df184bde7ca6083d8a33a2b1ce05e302685dc72,PMC,Hepatitis E Virus ORF2 Protein Activates the Pro-Apoptotic Gene CHOP and Anti-Apoptotic Heat Shock Proteins,http://dx.doi.org/10.1371/journal.pone.0025378,PMC3179511,21966512,CC BY,"BACKGROUND: Hepatitis E virus (HEV) is a non-enveloped plus-strand RNA virus that causes acute hepatitis. The capsid protein open reading frame 2 (ORF2) is known to induce endoplasmic reticulum stress in ORF2 expressing cells. METHODOLOGY/PRINCIPAL FINDINGS: In this study we found that HEV ORF2 activates the expression of the pro-apoptotic gene C/EBP homologous protein (CHOP). ORF2 stimulates the CHOP promoter mainly through AARE (amino acid response elements) and to a minor extent the ERSE (endoplasmic reticulum stress response elements). Activating transcription factor 4 (ATF4) protein binds and activates the AARE regulatory sites of the CHOP promoter. ORF2 expression also leads to increased phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) that in turn initiates the translation of ATF4 mRNA. The pro-apoptotic gene CHOP is an important trigger to initiate endoplasmic reticulum stress induced apoptosis. However, the activation of CHOP by ORF2 in this study did not induce apoptosis, nor did BCL2-associated X protein (Bax) translocate to mitochondria. Microarray analysis revealed an ORF2 specific increased expression of chaperones Hsp72, Hsp70B', and co-chaperone Hsp40. Co-immunoprecipitation (Co-IP) and in silico molecular docking analysis suggests that HEV ORF2 interacts with Hsp72. In addition, Hsp72 shows nuclear accumulation in ORF2 expressing cells. CONCLUSIONS/SIGNIFICANCE: These data provide new insight into simultaneously occurring counter-acting effects of HEV ORF2 that may be part of a strategy to prevent host suicide before completion of the viral replication cycle.",2011 Sep 23,"['John, Lijo', 'Thomas, Saijo', 'Herchenröder, Ottmar', 'Pützer, Brigitte M.', 'Schaefer, Stephan']",PLoS One,,,True
d1d1a8d96a13afa9c54ff26241095b55c0be7ff1,PMC,Chikungunya triggers an autophagic process which promotes viral replication,http://dx.doi.org/10.1186/1743-422X-8-432,PMC3179960,21902836,CC BY,"BACKGROUND: Chikungunya Virus (ChikV) surprised by a massive re-emerging outbreak in Indian Ocean in 2006, reaching Europe in 2007 and exhibited exceptional severe physiopathology in infants and elderly patients. In this context, it is important to analyze the innate immune host responses triggered against ChikV. Autophagy has been shown to be an important component of the innate immune response and is involved in host defense elimination of different pathogens. However, the autophagic process was recently observed to be hijacked by virus for their own replication. Here we provide the first evidence that hallmarks of autophagy are specifically found in HEK.293 infected cells and are involved in ChikV replication. METHODS: To test the capacity of ChikV to mobilize the autophagic machinery, we performed fluorescence microscopy experiments on HEK.GFP.LC3 stable cells, and followed the LC3 distribution during the time course of ChikV infection. To confirm this, we performed electron microscopy on HEK.293 infected cells. To test the effect of ChikV-induced-autophagy on viral replication, we blocked the autophagic process, either by pharmacological (3-MA) or genetic inhibition (siRNA against the transcript of Beclin 1, an autophagic protein), and analyzed the percentage of infected cells and the viral RNA load released in the supernatant. Moreover, the effect of induction of autophagy by Rapamycin on viral replication was tested. RESULTS: The increasing number of GFP-LC3 positive cells with a punctate staining together with the enhanced number of GFP-LC3 dots per cell showed that ChikV triggered an autophagic process in HEK.293 infected cells. Those results were confirmed by electron microscopy analysis since numerous membrane-bound vacuoles characteristic of autophagosomes were observed in infected cells. Moreover, we found that inhibition of autophagy, either by biochemical reagent and RNA interference, dramatically decreases ChikV replication. CONCLUSIONS: Taken together, our results suggest that autophagy may play a promoting role in ChikV replication. Investigating in details the relationship between autophagy and viral replication will greatly improve our knowledge of the pathogenesis of ChikV and provide insight for the design of candidate antiviral therapeutics.",2011 Sep 8,"['Krejbich-Trotot, Pascale', 'Gay, Bernard', 'Li-Pat-Yuen, Ghislaine', 'Hoarau, Jean-Jacques', 'Jaffar-Bandjee, Marie-Christine', 'Briant, Laurence', 'Gasque, Philippe', 'Denizot, Mélanie']",Virol J,,,True
264e7bc2caec36fca2b89d1f21198b8abb4a2d3e,PMC,Leukocyte- and Platelet-Derived Microvesicle Interactions following In Vitro and In Vivo Activation of Toll-Like Receptor 4 by Lipopolysaccharide,http://dx.doi.org/10.1371/journal.pone.0025504,PMC3180459,21966536,CC BY,"BACKGROUND: Pro-coagulant membrane microvesicles (MV) derived from platelets and leukocytes are shed into the circulation following receptor-mediated activation, cell-cell interaction, and apoptosis. Platelets are sentinel markers of toll-like receptor 4 (TLR4) activation. Experiments were designed to evaluate the time course and mechanism of direct interactions between platelets and leukocytes following acute activation of TLR4 by bacterial lipopolysaccharide (LPS). METHODOLOGY/PRINCIPAL FINDINGS: Blood from age-matched male and female wild type (WT) and TLR4 gene deleted (dTLR4) mice was incubated with ultra-pure E. coli LPS (500 ng/ml) for up to one hour. At designated periods, leukocyte antigen positive platelets, platelet antigen positive leukocytes and cell-derived MV were quantified by flow cytometry. Numbers of platelet- or leukocyte-derived MV did not increase within one hour following in vitro exposure of blood to LPS. However, with LPS stimulation numbers of platelets staining positive for both platelet- and leukocyte-specific antigens increased in blood derived from WT but not dTLR4 mice. This effect was blocked by inhibition of TLR4 signaling mediated by My88 and TRIF. Seven days after a single intravenous injection of LPS (500 ng/mouse or 20 ng/gm body wt) to WT mice, none of the platelets stained for leukocyte antigen. However, granulocytes, monocytes and apoptotic bodies stained positive for platelet antigens. CONCLUSIONS/SIGNIFICANCE: Within one hour of exposure to LPS, leukocytes exchange surface antigens with platelets through TLR4 activation. In vivo, leukocyte expression of platelet antigen is retained after a single exposure to LPS following turn over of the platelet pool. Acute expression of leukocyte antigen on platelets within one hour of exposure to LPS and the sustained expression of platelet antigen on leukocytes following a single acute exposure to LPS in vivo explains, in part, associations of platelets and leukocytes in response to bacterial infection and changes in thrombotic propensity of the blood.",2011 Sep 26,"['Xiong, Jing', 'Miller, Virginia M.', 'Hunter, Larry W.', 'Li, Yunman', 'Jayachandran, Muthuvel']",PLoS One,,,True
d336ffee34085032c158363c77b69204c58ca85a,PMC,"Type III IFN Receptor Expression and Functional Characterisation in the Pteropid Bat, Pteropus alecto",http://dx.doi.org/10.1371/journal.pone.0025385,PMC3181264,21980438,CC BY,"Bats are rich reservoir hosts for a variety of viruses, many of which are capable of spillover to other susceptible mammals with lethal consequences. The ability of bats to remain asymptomatic to viral infection may be due to the rapid control of viral replication very early in the immune response through innate antiviral mechanisms. Type I and III interferons (IFNs) represent the first line of defence against viral infection in mammals, with both families of IFNs present in pteropid bats. To obtain further insight into the type III IFN system in bats, we describe the characterization of the type III IFN receptor (IFNλR) in the black flying fox, P. alecto with the characterization of IFNλR1 and IL10R2 genes that make up the type III IFN receptor complex. The bat IFNλR complex has a wide tissue distribution and at the cellular level, both epithelial and immune cells are responsive to IFN-λ treatment. Furthermore, we demonstrate that the bat IFNλR1 chain acts as a functional receptor. To our knowledge, this report represents the first description of an IFN receptor in any species of bat. The responsiveness of bat cells to IFN-λ support a role for the type III IFN system by epithelial and immune cells in bats.",2011 Sep 27,"['Zhou, Peng', 'Cowled, Chris', 'Marsh, Glenn A.', 'Shi, Zhengli', 'Wang, Lin-Fa', 'Baker, Michelle L.']",PLoS One,,,True
579c99c1f830a59ff493ef9a08875f2e4ae2c405,PMC,Discovery and Genomic Characterization of a Novel Ovine Partetravirus and a New Genotype of Bovine Partetravirus,http://dx.doi.org/10.1371/journal.pone.0025619,PMC3181347,21980506,CC BY,"Partetravirus is a recently described group of animal parvoviruses which include the human partetravirus, bovine partetravirus and porcine partetravirus (previously known as human parvovirus 4, bovine hokovirus and porcine hokovirus respectively). In this report, we describe the discovery and genomic characterization of partetraviruses in bovine and ovine samples from China. These partetraviruses were detected by PCR in 1.8% of bovine liver samples, 66.7% of ovine liver samples and 71.4% of ovine spleen samples. One of the bovine partetraviruses detected in the present samples is phylogenetically distinct from previously reported bovine partetraviruses and likely represents a novel genotype. The ovine partetravirus is a novel partetravirus and phylogenetically most related to the bovine partetraviruses. The genome organization is conserved amongst these viruses, including the presence of a putative transmembrane protein encoded by an overlapping reading frame in ORF2. Results from the present study provide further support to the classification of partetraviruses as a separate genus in Parvovirinae.",2011 Sep 27,"['Tse, Herman', 'Tsoi, Hoi-Wah', 'Teng, Jade L. L.', 'Chen, Xin-Chun', 'Liu, Haiying', 'Zhou, Boping', 'Zheng, Bo-Jian', 'Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Yuen, Kwok-Yung']",PLoS One,,,True
4b22e5535c1084bdf92e00eea6bf4e6bd9e246a7,PMC,Discovery and Genomic Characterization of a Novel Ovine Partetravirus and a New Genotype of Bovine Partetravirus,http://dx.doi.org/10.1371/journal.pone.0025619,PMC3181347,21980506,CC BY,"Partetravirus is a recently described group of animal parvoviruses which include the human partetravirus, bovine partetravirus and porcine partetravirus (previously known as human parvovirus 4, bovine hokovirus and porcine hokovirus respectively). In this report, we describe the discovery and genomic characterization of partetraviruses in bovine and ovine samples from China. These partetraviruses were detected by PCR in 1.8% of bovine liver samples, 66.7% of ovine liver samples and 71.4% of ovine spleen samples. One of the bovine partetraviruses detected in the present samples is phylogenetically distinct from previously reported bovine partetraviruses and likely represents a novel genotype. The ovine partetravirus is a novel partetravirus and phylogenetically most related to the bovine partetraviruses. The genome organization is conserved amongst these viruses, including the presence of a putative transmembrane protein encoded by an overlapping reading frame in ORF2. Results from the present study provide further support to the classification of partetraviruses as a separate genus in Parvovirinae.",2011 Sep 27,"['Tse, Herman', 'Tsoi, Hoi-Wah', 'Teng, Jade L. L.', 'Chen, Xin-Chun', 'Liu, Haiying', 'Zhou, Boping', 'Zheng, Bo-Jian', 'Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Yuen, Kwok-Yung']",PLoS One,,,False
f5dc4bad737644cb25aeb8e23ba999402b0df872,PMC,Calf health from birth to weaning. II. Management of diarrhoea in pre-weaned calves,http://dx.doi.org/10.1186/2046-0481-64-9,PMC3182126,21917151,CC BY,"Calfhood diseases have a major impact on the economic viability of cattle operations. The second of this three part review series considers the management of diarrhoeic diseases in pre-weaned calves. In neonatal calf diarrhoea, oral rehydration therapy is the single most important therapeutic measure to be carried out by the farmer and is usually successful if instigated immediately after diarrhoea has developed. Continued feeding of milk or milk replacer to diarrhoeic calves is important, to prevent malnourishment and weight loss in affected calves. Indiscriminative antibiotic treatment of uncomplicated diarrhoea is discouraged, whereas systemically ill calves can benefit from systemic antibiotic treatment for the prevention of septicaemia or concurrent diseases. Ancillary treatments and specific preventive measures are discussed. Eimeriosis has a high economic impact on the farming industries due to direct cost of treatment and calf losses, but especially due to decreased performance of clinically as well as sub-clinically affected animals. Emphasis lies on prophylactic or metaphylactic treatment, since the degree of damage to the intestinal mucosa once diarrhoea has developed, makes therapeutic intervention unrewarding.",2011 Sep 14,"['Lorenz, Ingrid', 'Fagan, John', 'More, Simon J']",Ir Vet J,,,True
ee6d70a53e3262cea6f85bd8b226f6b4c8b5f64b,PMC,"Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009",http://dx.doi.org/10.1371/journal.pone.0025738,PMC3183080,21980532,CC BY,"BACKGROUND: To date, there is little information that reflects the true extent of spread of the pH1N1/2009v influenza pandemic at the community level as infection often results in mild or no clinical symptoms. This study aimed at assessing through a prospective study, the attack rate of pH1N1/2009 virus in Reunion Island and risk factors of infection, during the 2009 season. METHODOLOGY/PRINCIPAL FINDINGS: A serosurvey was conducted during the 2009 austral winter, in the frame of a prospective population study. Pairs of sera were collected from 1687 individuals belonging to 772 households, during and after passage of the pandemic wave. Antibodies to pH1N1/2009v were titered using the hemagglutination inhibition assay (HIA) with titers ≥1/40 being considered positive. Seroprevalence during the first two weeks of detection of pH1N1/2009v in Reunion Island was 29.8% in people under 20 years of age, 35.6% in adults (20–59 years) and 73.3% in the elderly (≥60 years) (P<0.0001). Baseline corrected cumulative incidence rates, were 42.9%, 13.9% and 0% in these age groups respectively (P<0.0001). A significant decline in antibody titers occurred soon after the passage of the epidemic wave. Seroconversion rates to pH1N1/2009 correlated negatively with age: 63.2%, 39.4% and 16.7%, in each age group respectively (P<0.0001). Seroconversion occurred in 65.2% of individuals who were seronegative at inclusion compared to 6.8% in those who were initially seropositive. CONCLUSIONS: Seroincidence of pH1N1/2009v infection was three times that estimated from clinical surveillance, indicating that almost two thirds of infections occurring at the community level have escaped medical detection. People under 20 years of age were the most affected group. Pre-epidemic titers ≥1/40 prevented seroconversion and are likely protective against infection. A concern was raised about the long term stability of the antibody responses.",2011 Sep 29,"['Dellagi, Koussay', 'Rollot, Olivier', 'Temmam, Sarah', 'Salez, Nicolas', 'Guernier, Vanina', 'Pascalis, Hervé', 'Gérardin, Patrick', 'Fianu, Adrian', 'Lapidus, Nathanael', 'Naty, Nadège', 'Tortosa, Pablo', 'Boussaïd, Karim', 'Jaffar-Banjee, Marie-Christine', 'Filleul, Laurent', 'Flahault, Antoine', 'Carrat, Fabrice', 'Favier, Francois', 'de Lamballerie, Xavier']",PLoS One,,,True
7902723eb8b21baa5eef8703832de11cc242a43b,PMC,The sialic acid binding activity of the S protein facilitates infection by porcine transmissible gastroenteritis coronavirus,http://dx.doi.org/10.1186/1743-422X-8-435,PMC3184106,21910859,CC BY,"BACKGROUND: Transmissible gastroenteritis virus (TGEV) has a sialic acid binding activity that is believed to be important for enteropathogenicity, but that has so far appeared to be dispensable for infection of cultured cells. The aims of this study were to determine the effect of sialic acid binding for the infection of cultured cells under unfavorable conditions, and comparison of TGEV strains and mutants, as well as the avian coronavirus IBV concerning their dependence on the sialic acid binding activity. METHODS: The infectivity of different viruses was analyzed by a plaque assay after adsorption times of 5, 20, and 60 min. Prior to infection, cultured cells were either treated with neuraminidase to deplete sialic acids from the cell surface, or mock-treated. In a second approach, pre-treatment of the virus with porcine intestinal mucin was performed, followed by the plaque assay after a 5 min adsorption time. A student's t-test was used to verify the significance of the results. RESULTS: Desialylation of cells only had a minor effect on the infection by TGEV strain Purdue 46 when an adsorption period of 60 min was allowed for initiation of infection. However, when the adsorption time was reduced to 5 min the infectivity on desialylated cells decreased by more than 60%. A TGEV PUR46 mutant (HAD3) deficient in sialic acid binding showed a 77% lower titer than the parental virus after a 5 min adsorption time. After an adsorption time of 60 min the titer of HAD3 was 58% lower than that of TGEV PUR46. Another TGEV strain, TGEV Miller, and IBV Beaudette showed a reduction in infectivity after neuraminidase treatment of the cultured cells irrespective of the virion adsorption time. CONCLUSIONS: Our results suggest that the sialic acid binding activity facilitates the infection by TGEV under unfavorable environmental conditions. The dependence on the sialic acid binding activity for an efficient infection differs in the analyzed TGEV strains.",2011 Sep 12,"['Schwegmann-Weßels, Christel', 'Bauer, Sandra', 'Winter, Christine', 'Enjuanes, Luis', 'Laude, Hubert', 'Herrler, Georg']",Virol J,,,True
626109d4ae81ef0adea376ed72148cdf4e578ac9,PMC,"Welcome to Viruses: A New Open-Access, Multidisciplinary Forum for Virology",http://dx.doi.org/10.3390/v1010001,PMC3185460,21994533,CC BY,,2009 Apr 1,"Freed, Eric O.",Viruses,,,False
3edea664551396420ae233d6951c3a8a71c2870e,PMC,Human Bocavirus – Insights into a Newly Identified Respiratory Virus,http://dx.doi.org/10.3390/v1010003,PMC3185462,21994534,CC BY,"Human Bocavirus (HBoV) was discovered in 2005 using a molecular virus screening technique. It is often found in respiratory samples and is a likely cause for respiratory diseases in children. HBoV is distributed worldwide and has been found not only in respiratory samples, but also in feces, urine and serum. HBoV infections are mostly found in young children and coinfections with other respiratory viruses are often found, exacerbating the efforts to link HBoV to specific symptoms. The purpose of this review is to give an overview of recent HBoV research, highlighting some recent findings.",2009 Apr 21,"['Lüsebrink, Jessica', 'Wittleben, Felix', 'Schildgen, Verena', 'Schildgen, Oliver']",Viruses,,,True
d7ccfdff2703c29904f679dc26fc8fd3f162e402,PMC,An Economical Tandem Multiplex Real-Time PCR Technique for the Detection of a Comprehensive Range of Respiratory Pathogens,http://dx.doi.org/10.3390/v1010042,PMC3185464,21994537,CC BY,"This study used real-time PCR assays to screen small sample volumes for a comprehensive range of 35 respiratory pathogens. Initial thermocycling was limited to 20 cycles to avoid competition for reagents, followed by a secondary real-time multiplex PCR. Supplementary semi-nested human metapneumovirus and picornavirus PCR assays were required to complete the acute respiratory pathogen profile. Potential pathogens were detected in 85 (70%) of pernasal aspirates collected from 121 children with acute respiratory symptoms. Multiple pathogens were detected in 29 (24%) of those samples. The tandem multiplex real-time PCR was an efficient method for the rapid detection of multiple pathogens.",2009 Jun 8,"['Chidlow, Glenys R.', 'Harnett, Gerry B.', 'Shellam, Geoffrey R.', 'Smith, David W.']",Viruses,,,True
27b4bbbc97d4660bbfef9e12bf3c3b9790df9014,PMC,More and More Coronaviruses: Human Coronavirus HKU1,http://dx.doi.org/10.3390/v1010057,PMC3185465,21994538,CC BY,"After human coronaviruses OC43, 229E and NL63, human coronavirus HKU1 (HCoV-HKU1) is the fourth human coronavirus discovered. HCoV-HKU1 is a group 2a coronavirus that is still not cultivable. The G + C contents of HCoV-HKU1 genomes are 32%, the lowest among all known coronaviruses with complete genome sequences available. Among all coronaviruses, HCoV-HKU1 shows the most extreme codon usage bias, attributed most importantly to severe cytosine deamination. All HCoV-HKU1 genomes contain unique tandem copies of a 30-base acidic tandem repeat of unknown function at the N-terminus of nsp3 inside the acidic domain upstream of papain-like protease 1. Three genotypes, A, B and C, of HCoV-HKU1 and homologous recombination among their genomes, are observed. The incidence of HCoV-HKU1 infections is the highest in winter. Similar to other human coronaviruses, HCoV-HKU1 infections have been reported globally, with a median (range) incidence of 0.9 (0 – 4.4) %. HCoV-HKU1 is associated with both upper and lower respiratory tract infections that are mostly self-limiting. The most common method for diagnosing HCoV-HKU1 infection is RT-PCR or real-time RT-PCR using RNA extracted from respiratory tract samples such as nasopharyngeal aspirates (NPA). Both the pol and nucleocapsid genes have been used as the targets for amplification. Monoclonal antibodies have been generated for direct antigen detection in NPA. For antibody detection, Escherichia coli BL21 and baculovirus-expressed recombinant nucleocapsid of HCoV-HKU1 have been used for IgG and IgM detection in sera of patients and normal individuals, using Western blot and enzyme-linked immunoassay.",2009 Jun 11,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Yip, Cyril C. Y.', 'Huang, Yi', 'Yuen, Kwok-Yung']",Viruses,,,True
437df56a9488ff2c8be3754b2642fb688115a1b5,PMC,Significance of Coronavirus Mutants in Feces and Diseased Tissues of Cats Suffering from Feline Infectious Peritonitis,http://dx.doi.org/10.3390/v1020166,PMC3185486,21994544,CC BY,"The internal FECV→FIPV mutation theory and three of its correlates were tested in four sibs/half-sib kittens, a healthy contact cat, and in four unrelated cats that died of FIP at geographically disparate regions. Coronavirus from feces and extraintestinal FIP lesions from the same cat were always >99% related in accessory and structural gene sequences. SNPs and deletions causing a truncation of the 3c gene product were found in almost all isolates from the diseased tissues of the eight cats suffering from FIP, whereas most, but not all fecal isolates from these same cats had intact 3c genes. Other accessory and structural genes appeared normal in both fecal and lesional viruses. Deliterious mutations in the 3c gene were unique to each cat, indicating that they did not originate in one cat and were subsequently passed horizontally to the others. Compartmentalization of the parental and mutant forms was not absolute; virus of lesional type was sometimes found in feces of affected cats and virus identical to fecal type was occasionally identified in diseased tissues. Although 3c gene mutants in this study were not horizontally transmitted, the parental fecal virus was readily transmitted by contact from a cat that died of FIP to its housemate. There was a high rate of mutability in all structural and accessory genes both within and between cats, leading to minor genetic variants. More than one variant could be identified in both diseased tissues and feces of the same cat. Laboratory cats inoculated with a mixture of two closely related variants from the same FIP cat developed disease from one or the other variant, but not both. Significant genetic drift existed between isolates from geographically distinct regions of the Western US.",2009 Aug 26,"['Pedersen, Niels C.', 'Liu, Hongwei', 'Dodd, Kimberly A.', 'Pesavento, Patricia A.']",Viruses,,,True
d739cf97cba31e655d6c7438b864d94297f59ba3,PMC,Regulation of Innate Immune Responses by Bovine Herpesvirus 1 and Infected Cell Protein 0 (bICP0),http://dx.doi.org/10.3390/v1020255,PMC3185490,21994549,CC BY,"Bovine herpesvirus 1 (BoHV-1) infected cell protein 0 (bICP0) is an important transcriptional regulatory protein that stimulates productive infection. In transient transfection assays, bICP0 also inhibits interferon dependent transcription. bICP0 can induce degradation of interferon stimulatory factor 3 (IRF3), a cellular transcription factor that is crucial for activating beta interferon (IFN-β) promoter activity. Recent studies also concluded that interactions between bICP0 and IRF7 inhibit trans-activation of IFN-β promoter activity. The C3HC4 zinc RING (really important new gene) finger located near the amino terminus of bICP0 is important for all known functions of bICP0. A recombinant virus that contains a single amino acid change in a well conserved cysteine residue of the C3HC4 zinc RING finger of bICP0 grows poorly in cultured cells, and does not reactivate from latency in cattle confirming that the C3HC4 zinc RING finger is crucial for viral growth and pathogenesis. A bICP0 deletion mutant does not induce plaques in permissive cells, but induces autophagy in a cell type dependent manner. In summary, the ability of bICP0 to stimulate productive infection, and repress IFN dependent transcription plays a crucial role in the BoHV-1 infection cycle.",2009 Sep 7,"Jones, Clinton",Viruses,,,True
e1c4d9cdea7ddbf8cad8a101da840b3394c5303b,PMC,Plasmacytoid Dendritic Cells and the Control of Herpesvirus Infections,http://dx.doi.org/10.3390/v1030383,PMC3185500,21994554,CC BY,"Type-I interferons (IFN-I) are cytokines essential for vertebrate antiviral defense, including against herpesviruses. IFN-I have potent direct antiviral activities and also mediate a multiplicity of immunoregulatory functions, which can either promote or dampen antiviral adaptive immune responses. Plasmacytoid dendritic cells (pDCs) are the professional producers of IFN-I in response to many viruses, including all of the herpesviruses tested. There is strong evidence that pDCs could play a major role in the initial orchestration of both innate and adaptive antiviral immune responses. Depending on their activation pattern, pDC responses may be either protective or detrimental to the host. Here, we summarize and discuss current knowledge regarding pDC implication in the physiopathology of mouse and human herpesvirus infections, and we discuss how pDC functions could be manipulated in immunotherapeutic settings to promote health over disease.",2009 Oct 14,"['Baranek, Thomas', 'Zucchini, Nicolas', 'Dalod, Marc']",Viruses,,,True
ec4a332b863ec8c1bbf94d605b17c67acddf0889,PMC,Seroconversion to HCoV-NL63 in Rhesus Macaques,http://dx.doi.org/10.3390/v1030647,PMC3185515,21994563,CC BY,"HCoV-NL63 is a recently identified respiratory virus. Its pathogenesis has not been fully unraveled because an animal model is currently lacking. Here we examined whether rhesus macaques encounter HCoV-NL63 infections during life, by examining the levels of antibodies to HCoV-NL63 in time. The animals were followed for 7 up till 19 years, and in three animals we observed a steep rise in antibodies during follow up, indicative of a natural infection with HCoV-NL63.",2009 Oct 30,"['Dijkman, Ronald', 'Mulder, H. Lie', 'Rumping, Lynne', 'Kraaijvanger, Ilse', 'Deijs, Martin', 'Jebbink, Maarten F.', 'Verschoor, Ernst J.', 'van der Hoek, Lia']",Viruses,,,True
72d4e41eee56e6b1e8b7b361375c2e9160a6da49,PMC,Defective Interfering RNAs: Foes of Viruses and Friends of Virologists,http://dx.doi.org/10.3390/v1030895,PMC3185524,21994575,CC BY,"Defective interfering (DI) RNAs are subviral RNAs produced during multiplication of RNA viruses by the error-prone viral replicase. DI-RNAs are parasitic RNAs that are derived from and associated with the parent virus, taking advantage of viral-coded protein factors for their multiplication. Recent advances in the field of DI RNA biology has led to a greater understanding about generation and evolution of DI-RNAs as well as the mechanism of symptom attenuation. Moreover, DI-RNAs are versatile tools in the hands of virologists and are used as less complex surrogate templates to understand the biology of their helper viruses. The ease of their genetic manipulation has resulted in rapid discoveries on cis-acting RNA replication elements required for replication and recombination. DI-RNAs have been further exploited to discover host factors that modulate Tomato bushy stunt virus replication, as well as viral RNA recombination. This review discusses the current models on generation and evolution of DI-RNAs, the roles of viral and host factors in DI-RNA replication, and the mechanisms of disease attenuation.",2009 Nov 10,"['Pathak, Kunj B.', 'Nagy, Peter D.']",Viruses,,,True
f0d935a0e0f1360bf4166b9db8e4cddf67aa9cd7,PMC,Activation of the Antiviral Kinase PKR and Viral Countermeasures,http://dx.doi.org/10.3390/v1030523,PMC3185532,21994559,CC BY,"The interferon-induced double-stranded (ds)RNA-dependent protein kinase (PKR) limits viral replication by an eIF2α-mediated block of translation. Although many negative-strand RNA viruses activate PKR, the responsible RNAs have long remained elusive, as dsRNA, the canonical activator of PKR, has not been detected in cells infected with such viruses. In this review we focus on the activating RNA molecules of different virus families, in particular the negative-strand RNA viruses. We discuss the recently identified non-canonical activators 5′-triphosphate RNA and the vRNP of influenza virus and give an update on strategies of selected RNA and DNA viruses to prevent activation of PKR.",2009 Oct 27,"['Dauber, Bianca', 'Wolff, Thorsten']",Viruses,,,True
ce07f8b5cfe254e66c5d9f174dd1f3208a459520,PMC,All Known Human Rhinovirus Species Are Present in Sputum Specimens of Military Recruits During Respiratory Infection,http://dx.doi.org/10.3390/v1031178,PMC3185535,21994588,CC BY,"Human rhinoviruses (HRV) are known to cause common cold as well as more complicated respiratory infections. HRV species -A, -B and -C have all been associated with lower respiratory infections and exacerbations of asthma. However, the type distribution of strains connected to different kinds of lower respiratory conditions is not clearly known. We have analysed the presence of HRV in sputum specimens derived from military recruits with and without pre-diagnosed asthma at times of acute respiratory infection (CIAS Study, 2004–2005). The analysis was performed with HRV and HEV real-time RT-PCR assays. Subsequently we studied type distribution of HRV strains by genetic typing in the VP4/VP2 genomic region. In total 146 (38.8%) specimens were HRV-positive and 36 (9.3%) HEV-positive. No difference was found in HRV detection between the asthmatic vs. non-asthmatic patients. Most of the genetically typed strains, 18 (62.1%), belonged to HRV-A, while HRV-B strains constituted five (17.2%) of the HRV-positive strains. HRV-C strain was typed four times from the HRV-positive cases and a HEV-D strain twice. We further typed six HEV positive strains in the partial VP1 region. Three of these belonged to HRV-A and three to HEV-D. HRV-A strains were discovered throughout the study period, while HRV-C strains originated from winter and spring specimens. Interestingly, four out of five typed HRV-B strains originated from the summer season specimens.",2009 Dec 4,"['Savolainen-Kopra, Carita', 'Blomqvist, Soile', 'Kaijalainen, Svetlana', 'Jounio, Ulla', 'Juvonen, Raija', 'Peitso, Ari', 'Saukkoriipi, Annika', 'Vainio, Olli', 'Hovi, Tapani', 'Roivainen, Merja']",Viruses,,,True
7e6fc218bd723f70d305eadff23e036875076250,PMC,WU Polyomavirus (WUPyV): A Recently Detected Virus Causing Respiratory Disease?,http://dx.doi.org/10.3390/v1030678,PMC3185540,21994565,CC BY,"The WU polyomavirus (WUPyV) is a novel member of the family Polyomaviridae recently detected in respiratory tract specimens by shotgun sequencing. Intriguingly, viral genome has been detected in 0.4% to 11.5% of respiratory tract specimens from children with respiratory disease. The levels of co-infection with established respiratory viruses were in the range between 30.8% and 91.7%. Moreover, some studies report detection of WUPyV in stool or serum. So far, WUPyV infections can not be distinguished from other viral infections by means of clinical symptoms. Respiratory tract disease like pneumonia or bronchitis is frequently observed in patients harbouring WUPyV. Detection of viremia suggests systemic infections. However, the available data do not prove WUPyV to be a human pathogen. Further investigations are necessary.",2009 Nov 4,"['Kleines, Michael', 'Häusler, Martin', 'Krüttgen, Alexander', 'Scheithauer, Simone']",Viruses,,,True
789d8f8e801484da5740462f088a39aaf4e2a411,PMC,Maturation Pathways of Cross-Reactive HIV-1 Neutralizing Antibodies,http://dx.doi.org/10.3390/v1030802,PMC3185542,21994570,CC BY,"Several human monoclonal antibodies (hmAbs) and antibody fragments, including the best characterized in terms of structure-function b12 and Fab X5, exhibit relatively potent and broad HIV-1 neutralizing activity. However, the elicitation of b12 or b12-like antibodies in vivo by vaccine immunogens based on the HIV-1 envelope glycoprotein (Env) has not been successful. B12 is highly divergent from the closest corresponding germline antibody while X5 is less divergent. We have hypothesized that the relatively high degree of specific somatic hypermutations may preclude binding of the HIV-1 envelope glycoprotein (Env) to closest germline antibodies, and that identifying antibodies that are intermediates in the pathways to maturation could help design novel vaccine immunogens to guide the immune system for their enhanced elicitation. In support of this hypothesis we have previously found that a germline-like b12 (monovalent and bivalent scFv as an Fc fusion protein or IgG) lacks measurable binding to an Env as measured by ELISA with a sensitivity in the μM range [1]; here we present evidence confirming and expanding these findings for a panel of Envs. In contrast, a germline-like scFv X5 bound Env with high (nM) affinity. To begin to explore the maturation pathways of these antibodies we identified several possible b12 intermediate antibodies and tested their neutralizing activity. These intermediate antibodies neutralized only some HIV-1 isolates and with relatively weak potency. In contrast, germline-like scFv X5 neutralized a subset of the tested HIV-1 isolates with comparable efficiencies to that of the mature X5. These results could help explain the relatively high immunogenicity of the coreceptor binding site on gp120 and the abundance of CD4-induced (CD4i) antibodies in HIV-1-infected patients (X5 is a CD4i antibody) as well as the maturation pathway of X5. They also can help identify antigens that can bind specifically to b12 germline and intermediate antibodies that together with Envs could be used as a conceptually novel type of candidate vaccines. Such candidate vaccines based on two or more immunogens could help guiding the immune system through complex maturation pathways for elicitation of antibodies that are similar or identical to antibodies with known properties.",2009 Nov 6,"['Xiao, Xiaodong', 'Chen, Weizao', 'Feng, Yang', 'Dimitrov, Dimiter S.']",Viruses,,,True
1c8afcb822dac8e8e5b33a85c2c2e9c7cc24a25a,PMC,Complete Nucleotide Analysis of the Structural Genome of the Infectious Bronchitis Virus Strain Md27 Reveals its Mosaic Nature,http://dx.doi.org/10.3390/v1031166,PMC3185546,21994587,CC BY,"Infectious bronchitis virus (IBV) causes highly contagious respiratory or urogenital tract diseases in chickens. The Maryland 27(Md27) strain was first isolated in 1976 from diseased chicken flocks in the Delmarva Peninsula region. To understand the genetic diversity and phylogenetic relationship of existing strains with Md27, the complete nucleotide sequence of the 3′end coding region (∼7.2 kb) of Md27 was determined and compared with other IBV strains and coronaviruses. It has the same S-3-M-5-N-3′ gene order, as is the case of other IBV strains. The spike gene of Md27 exhibits 97% identity with the SE17 strain. There are deletions at the spike gene, non-coding region between M and 5 genes, and at the 3′ untranslated region (UTR), which is different from Ark-like strains. Phylogenetic analysis and sequence alignments demonstrate that Md27 is a chimera containing different gene segments that are most closely related to the SE17, Conn and JMK strains. This current study provides evidence for genomic mutations and intergenic recombination that have taken place in the evolution of IBV strain Md27.",2009 Dec 4,"['Ammayappan, Arun', 'Vakharia, Vikram N.']",Viruses,,,True
ab26098d2e9876c05c8c1fd3d30d45a749b944e3,PMC,The Development of an AIDS Mucosal Vaccine,http://dx.doi.org/10.3390/v2010283,PMC3185548,21994611,CC BY,"It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible human hosts through open mucosal surfaces. Human immunodeficiency virus type one (HIV-1), a mainly sexually transmitted virus, also primarily targets the vaginal and gastrointestinal mucosa as entry sites for viral transmission, seeding, replication and amplification. Since HIV-1 establishes its early replication in vaginal or rectal mucosal tissues, the induction of sufficient mucosal immunity at the initial site of HIV-1 transmission becomes essential for a protective vaccine. However, despite the fact that current conventional vaccine strategies have remained unsuccessful in preventing HIV-1 infection, sufficient financial support and resources have yet to be given to develop a vaccine able to elicit protective mucosal immunity against sexual transmissions. Interestingly, Chinese ancestors invented variolation through intranasal administration about one thousand years ago, which led to the discovery of a successful smallpox vaccine and the final eradication of the disease. It is the hope for all mankind that the development of a mucosal AIDS vaccine will ultimately help control the AIDS pandemic. In order to discover an effective mucosal AIDS vaccine, it is necessary to have a deep understanding of mucosal immunology and to test various mucosal vaccination strategies.",2010 Jan 22,"['Tang, Xian', 'Chen, Zhiwei']",Viruses,,,True
40afe56736a9733a103c22570b574165d7d38edd,PMC,Antiviral Properties of ISG15,http://dx.doi.org/10.3390/v2102154,PMC3185569,21994614,CC BY,"The type I interferon system plays a critical role in limiting the spread of viral infection. Viruses induce the production of interferon (IFN), which after binding to the IFN-α/β receptor (IFNAR), and triggering of the JAK/STAT signaling cascade, results in the induction of interferon-stimulated genes (ISGs). These ISGs function to inhibit viral replication and to regulate the host immune response. Among these ISGs, the ubiquitin-like molecule, ISG15, is one of the most strongly induced proteins. Similar to ubiquitin, through an IFN induced conjugation cascade, ISG15 is covalently linked to a variety of cellular proteins, suggesting regulation of different cellular processes. Studies performed over the past several years have shown that ISG15 plays a central role in the host’s antiviral response against many viruses. Mice lacking ISG15 display increased susceptibility to multiple viruses. Furthermore, several viruses have developed immune evasion strategies that directly target the ISG15 pathway. Work is now underway to determine the mechanism by which ISG15 functions as an antiviral molecule, such that therapies targeting this pathway can be developed in the future.",2010 Sep 28,"Lenschow, Deborah J.",Viruses,,,True
796abc8d89c17b85820bfd4a6466dc9cda531e4b,PMC,Poxvirus Exploitation of the Ubiquitin-Proteasome System,http://dx.doi.org/10.3390/v2102356,PMC3185573,21994622,CC BY,"Ubiquitination plays a critical role in many cellular processes. A growing number of viruses have evolved strategies to exploit the ubiquitin-proteasome system, including members of the Poxviridae family. Members of the poxvirus family have recently been shown to encode BTB/kelch and ankyrin/F-box proteins that interact with cullin-3 and cullin-1 based ubiquitin ligases, respectively. Multiple members of the poxvirus family also encode ubiquitin ligases with intrinsic activity. This review describes the numerous mechanisms that poxviruses employ to manipulate the ubiquitin-proteasome system.",2010 Oct 19,"['Barry, Michele', 'van Buuren, Nicholas', 'Burles, Kristin', 'Mottet, Kelly', 'Wang, Qian', 'Teale, Alastair']",Viruses,,,True
48764be42938595e40cb6c0bc73fc891a6e962e1,PMC,Buying Time—The Immune System Determinants of the Incubation Period to Respiratory Viruses,http://dx.doi.org/10.3390/v2112541,PMC3185581,21994630,CC BY,"Respiratory viruses cause disease in humans characterized by an abrupt onset of symptoms. Studies in humans and animal models have shown that symptoms are not immediate and appear days or even weeks after infection. Since the initial symptoms are a manifestation of virus recognition by elements of the innate immune response, early virus replication must go largely undetected. The interval between infection and the emergence of symptoms is called the incubation period and is widely used as a clinical score. While incubation periods have been described for many virus infections the underlying mechanism for this asymptomatic phase has not been comprehensively documented. Here we review studies of the interaction between human pathogenic respiratory RNA viruses and the host with a particular emphasis on the mechanisms used by viruses to inhibit immunity. We discuss the concept of the “stealth phase”, defined as the time between infection and the earliest detectable inflammatory response. We propose that the “stealth phase” phenomenon is primarily responsible for the suppression of symptoms during the incubation period and results from viral antagonism that inhibits major pathways of the innate immune system allowing an extended time of unhindered virus replication.",2010 Nov 18,"['Hermesh, Tamar', 'Moltedo, Bruno', 'López, Carolina B.', 'Moran, Thomas M.']",Viruses,,,True
81ef62610df1e107053f06e2fa745a33912e299f,PMC,Making of Viral Replication Organelles by Remodeling Interior Membranes,http://dx.doi.org/10.3390/v2112436,PMC3185585,21994625,CC BY,"Positive-stranded RNA (+RNA) viruses exploit host cell machinery by subverting host proteins and membranes and altering cellular pathways during infection. To achieve robust replication, some +RNA viruses, such as poliovirus (PV), build special intracellular compartments, called viral replication organelles. A recent work from the Altan-Bonnett laboratory [1] gave new insights into the formation of poliovirus replication organelles, which are unique subcellular structures containing many individual replication complexes as a result of dynamic cellular membrane remodeling.",2010 Nov 5,"['Sasvari, Zsuzsanna', 'Nagy, Peter D.']",Viruses,,,True
67448222647675616fa788dcf9426cefa3fd9575,PMC,Monkeypox Virus Infections in Small Animal Models for Evaluation of Anti-Poxvirus Agents,http://dx.doi.org/10.3390/v2122763,PMC3185589,21994638,CC BY,"An ideal animal model for the study of a human disease is one which utilizes a route of infection that mimics the natural transmission of the pathogen; the ability to obtain disease with an infectious dose equivalent to that causing disease in humans; as well having a disease course, morbidity and mortality similar to that seen with human disease. Additionally, the animal model should have a mode(s) of transmission that mimics human cases. The development of small animal models for the study of monkeypox virus (MPXV) has been quite extensive for the relatively short period of time this pathogen has been known, although only a few of these models have been used to study anti-poxvirus agents. We will review those MPXV small animal models that have been developed thus far for the study of therapeutic agents.",2010 Dec 20,"['Hutson, Christina L.', 'Damon, Inger K.']",Viruses,,,True
c59f056b663000ffe9a935dbc10fcd847dd67867,PMC,Viral Genomics and Bioinformatics,http://dx.doi.org/10.3390/v2122587,PMC3185590,21994632,CC BY,,2010 Nov 30,"Seto, Donald",Viruses,,,True
efe13a8d42b60ef9f7387ea539a1b2eeb5f80101,PMC,Hantaviruses in the Americas and Their Role as Emerging Pathogens,http://dx.doi.org/10.3390/v2122559,PMC3185593,21994631,CC BY,"The continued emergence and re-emergence of pathogens represent an ongoing, sometimes major, threat to populations. Hantaviruses (family Bunyaviridae) and their associated human diseases were considered to be confined to Eurasia, but the occurrence of an outbreak in 1993–94 in the southwestern United States led to a great increase in their study among virologists worldwide. Well over 40 hantaviral genotypes have been described, the large majority since 1993, and nearly half of them pathogenic for humans. Hantaviruses cause persistent infections in their reservoir hosts, and in the Americas, human disease is manifest as a cardiopulmonary compromise, hantavirus cardiopulmonary syndrome (HCPS), with case-fatality ratios, for the most common viral serotypes, between 30% and 40%. Habitat disturbance and larger-scale ecological disturbances, perhaps including climate change, are among the factors that may have increased the human caseload of HCPS between 1993 and the present. We consider here the features that influence the structure of host population dynamics that may lead to viral outbreaks, as well as the macromolecular determinants of hantaviruses that have been regarded as having potential contribution to pathogenicity.",2010 Nov 25,"['Hjelle, Brian', 'Torres-Pérez, Fernando']",Viruses,,,True
738d255294896f43d6ac7546a891900714ef1d51,PMC,PEGylated Adenoviruses: From Mice to Monkeys,http://dx.doi.org/10.3390/v2020468,PMC3185605,21994645,CC BY,"Covalent modification with polyethylene glycol (PEG), a non-toxic polymer used in food, cosmetic and pharmaceutical preparations for over 60 years, can profoundly influence the pharmacokinetic, pharmacologic and toxciologic profile of protein and peptide-based therapeutics. This review summarizes the history of PEGylation and PEG chemistry and highlights the value of this technology in the context of the design and development of recombinant viruses for gene transfer, vaccination and diagnostic purposes. Specific emphasis is placed on the application of this technology to the adenovirus, the most potent viral vector with the most highly characterized toxicity profile to date, in several animal models.",2010 Feb 1,"['Wonganan, Piyanuch', 'Croyle, Maria A.']",Viruses,,,True
00cb1a95986171a256f5ef14701bd8f571221a28,PMC,How Flaviviruses Activate and Suppress the Interferon Response,http://dx.doi.org/10.3390/v2020676,PMC3185611,21994652,CC BY,"The flavivirus genus includes viruses with a remarkable ability to produce disease on a large scale. The expansion and increased endemicity of dengue and West Nile viruses in the Americas exemplifies their medical and epidemiological importance. The rapid detection of viral infection and induction of the innate antiviral response are crucial to determining the outcome of infection. The intracellular pathogen receptors RIG-I and MDA5 play a central role in detecting flavivirus infections and initiating a robust antiviral response. Yet, these viruses are still capable of producing acute illness in humans. It is now clear that flaviviruses utilize a variety of mechanisms to modulate the interferon response. The non-structural proteins of the various flaviviruses reduce expression of interferon dependent genes by blocking phosphorylation, enhancing degradation or down-regulating expression of major components of the JAK/STAT pathway. Recent studies indicate that interferon modulation is an important factor in the development of severe flaviviral illness. This suggests that an increased understanding of viral-host interactions will facilitate the development of novel therapeutics to treat these viral infections and improved biological models to study flavivirus pathogenesis.",2010 Feb 23,"['Muñoz-Jordán, Jorge L.', 'Fredericksen, Brenda L.']",Viruses,,,True
390b508dfbde0fbf9b91e67cc77fcd3bf0e391ed,PMC,An Ecological and Conservation Perspective on Advances in the Applied Virology of Zoonoses,http://dx.doi.org/10.3390/v3040379,PMC3185704,21994738,CC BY,"The aim of this manuscript is to describe how modern advances in our knowledge of viruses and viral evolution can be applied to the fields of disease ecology and conservation. We review recent progress in virology and provide examples of how it is informing both empirical research in field ecology and applied conservation. We include a discussion of needed breakthroughs and ways to bridge communication gaps between the field and the lab. In an effort to foster this interdisciplinary effort, we have also included a table that lists the definitions of key terms. The importance of understanding the dynamics of zoonotic pathogens in their reservoir hosts is emphasized as a tool to both assess risk factors for spillover and to test hypotheses related to treatment and/or intervention strategies. In conclusion, we highlight the need for smart surveillance, viral discovery efforts and predictive modeling. A shift towards a predictive approach is necessary in today’s globalized society because, as the 2009 H1N1 pandemic demonstrated, identification post-emergence is often too late to prevent global spread. Integrating molecular virology and ecological techniques will allow for earlier recognition of potentially dangerous pathogens, ideally before they jump from wildlife reservoirs into human or livestock populations and cause serious public health or conservation issues.",2011 Apr 15,"['Vandegrift, Kurt J.', 'Wale, Nina', 'Epstein, Jonathan H.']",Viruses,,,True
2965d872997d38cdfcde8b9bb17c8c659b0a16f7,PMC,siRNA for Influenza Therapy,http://dx.doi.org/10.3390/v2071448,PMC3185718,21994689,CC BY,"Influenza virus is one of the most prevalent and ancient infections in humans. About a fifth of world’s population is infected by influenza virus annually, leading to high morbidity and mortality, particularly in infants, the elderly and the immunocompromised. In the US alone, influenza outbreaks lead to roughly 30,000 deaths each year. Current vaccines and anti-influenza drugs are of limited use due to high mutation rate of the virus and side effects. In recent years, RNA interference, triggered by synthetic short interfering RNA (siRNA), has rapidly evolved as a potent antiviral regimen. Properly designed siRNAs have been shown to function as potent inhibitors of influenza virus replication. The siRNAs outperform traditional small molecule antivirals in a number of areas, such as ease of design, modest cost, and fast turnaround. Although specificity and tissue delivery remain major bottlenecks in the clinical applications of RNAi in general, intranasal application of siRNA against respiratory viruses including, but not limited to influenza virus, has experienced significant success and optimism, which is reviewed here.",2010 Jul 9,"Barik, Sailen",Viruses,,,True
55f46f193444dd9f891aab9b4320f38d5161f8ba,PMC,Possibilities for RNA Interference in Developing Hepatitis C Virus Therapeutics,http://dx.doi.org/10.3390/v2081647,PMC3185727,21994699,CC BY,"The discovery and characterization of the RNA interference (RNAi) pathway has been one of the most important scientific developments of the last 12 years. RNAi is a cellular pathway wherein small RNAs control the expression of genes by either degrading homologous RNAs or preventing the translation of RNAs with partial homology. It has impacted basic biology on two major fronts. The first is the discovery of microRNAs (miRNAs), which regulate almost every cellular process and are required for some viral infections, including hepatitis C virus (HCV). The second front is the use of small interfering RNAs (siRNAs) as the first robust tool for mammalian cellular genetics. This has led to the identification of hundreds of cellular genes that are important for HCV infection. There is now a major push to adapt RNAi technology to the clinic. In this review, we explore the impact of RNAi in understanding HCV biology, the progress in design of RNAi-based therapeutics for HCV, and remaining obstacles.",2010 Aug 6,"['Berger, Kristi L.', 'Randall, Glenn']",Viruses,,,True
42c4f1b128cea03599c36e89eff62afa7e02caa2,PMC,Coronavirus Genomics and Bioinformatics Analysis,http://dx.doi.org/10.3390/v2081803,PMC3185738,21994708,CC BY,"The drastic increase in the number of coronaviruses discovered and coronavirus genomes being sequenced have given us an unprecedented opportunity to perform genomics and bioinformatics analysis on this family of viruses. Coronaviruses possess the largest genomes (26.4 to 31.7 kb) among all known RNA viruses, with G + C contents varying from 32% to 43%. Variable numbers of small ORFs are present between the various conserved genes (ORF1ab, spike, envelope, membrane and nucleocapsid) and downstream to nucleocapsid gene in different coronavirus lineages. Phylogenetically, three genera, Alphacoronavirus, Betacoronavirus and Gammacoronavirus, with Betacoronavirus consisting of subgroups A, B, C and D, exist. A fourth genus, Deltacoronavirus, which includes bulbul coronavirus HKU11, thrush coronavirus HKU12 and munia coronavirus HKU13, is emerging. Molecular clock analysis using various gene loci revealed that the time of most recent common ancestor of human/civet SARS related coronavirus to be 1999–2002, with estimated substitution rate of 4×10(−4) to 2×10(−2) substitutions per site per year. Recombination in coronaviruses was most notable between different strains of murine hepatitis virus (MHV), between different strains of infectious bronchitis virus, between MHV and bovine coronavirus, between feline coronavirus (FCoV) type I and canine coronavirus generating FCoV type II, and between the three genotypes of human coronavirus HKU1 (HCoV-HKU1). Codon usage bias in coronaviruses were observed, with HCoV-HKU1 showing the most extreme bias, and cytosine deamination and selection of CpG suppressed clones are the two major independent biological forces that shape such codon usage bias in coronaviruses.",2010 Aug 24,"['Woo, Patrick C. Y.', 'Huang, Yi', 'Lau, Susanna K. P.', 'Yuen, Kwok-Yung']",Viruses,,,True
4e1119e030d3d053276c55c9220a388d743bb0e3,PMC,Systems-Biology Approaches to Discover Anti-Viral Effectors of the Human Innate Immune Response,http://dx.doi.org/10.3390/v3071112,PMC3185791,21994773,CC BY,"Virus infections elicit an immediate innate response involving antiviral factors. The activities of some of these factors are, in turn, blocked by viral countermeasures. The ensuing battle between the host and the viruses is crucial for determining whether the virus establishes a foothold and/or induces adaptive immune responses. A comprehensive systems-level understanding of the repertoire of anti-viral effectors in the context of these immediate virus-host responses would provide significant advantages in devising novel strategies to interfere with the initial establishment of infections. Recent efforts to identify cellular factors in a comprehensive and unbiased manner, using genome-wide siRNA screens and other systems biology “omics” methodologies, have revealed several potential anti-viral effectors for viruses like Human immunodeficiency virus type 1 (HIV-1), Hepatitis C virus (HCV), West Nile virus (WNV), and influenza virus. This review describes the discovery of novel viral restriction factors and discusses how the integration of different methods in systems biology can be used to more comprehensively identify the intimate interactions of viruses and the cellular innate resistance.",2011 Jul 11,"['Münk, Carsten', 'Sommer, Andreas F.R.', 'König, Renate']",Viruses,,,True
8b9bec3c317211d347532e8991d2494098d16dc2,PMC,Dengue Virus and Autophagy,http://dx.doi.org/10.3390/v3081332,PMC3185800,21994782,CC BY,"Several independent groups have published that autophagy is required for optimal RNA replication of dengue virus (DENV). Initially, it was postulated that autophagosomes might play a structural role in replication complex formation. However, cryo-EM tomography of DENV replication complexes showed that DENV replicates on endoplasmic reticulum (ER) cisternae invaginations and not on classical autophagosomes. Recently, it was reported that autophagy plays an indirect role in DENV replication by modulating cellular lipid metabolism. DENV-induced autophagosomes deplete cellular triglycerides that are stored in lipid droplets, leading to increased β-oxidation and energy production. This is the first example of a virus triggering autophagy to modulate cellular physiology. In this review, we summarize these data and discuss new questions and implications for autophagy during DENV replication.",2011 Aug 4,"['Heaton, Nicholas S.', 'Randall, Glenn']",Viruses,,,True
29cc49c0a88d00ecc54d45ff5bf9128e47e9a444,PMC,The Prevalence and Significance of HTLV-I/II Seroindeterminate Western Blot Patterns,http://dx.doi.org/10.3390/v3081320,PMC3185804,21994781,CC BY,"Human T-lymphotropic virus type I (HTLV-I) infects an estimated 15–20 million persons worldwide. A number of diseases have been associated with the virus including adult T-cell leukemia (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-I uveitis, and HTLV-I-associated infective dermatitis. Once it was shown that there is an increased risk for developing HAM/TSP associated with blood transfusion, screening for HTLV-1 among blood banks was implemented in Japan, United States, France, and the Netherlands. This process includes detection by an enzyme immunoassay (EIA) followed by a confirmatory Western blot (WB) in which recombinant proteins specific for HTLV-I Env glycoproteins are incorporated into WB strips. HTLV-I seropositive results are defined by the presence of antibodies against either gp46 or gp62/68 (both Env protein bands) and either p19, p24, or p53 (one of the gag bands). HTLV-II seropositivity is confirmed by the presence of rgp46-II. However, numerous cases have been documented in which serum samples are reactive by EIA, but an incomplete banding pattern is displayed by subsequent confirmatory WB. Although the significance of these HTLV-I/II seroindeterminates is unclear, it may suggest a much higher incidence of exposure to HTLV-I/II than previously estimated.",2011 Aug 2,"['Abrams, Anna', 'Akahata, Yoshimi', 'Jacobson, Steven']",Viruses,,,True
120aebc8b074393770c411ebf774ed18a5a2a1da,PMC,Impact of the Autophagy Machinery on Hepatitis C Virus Infection,http://dx.doi.org/10.3390/v3081342,PMC3185811,21994783,CC BY,"Autophagy is a cellular process that catabolizes cytoplasmic components and maintains energy homeostasis. As a stress response, the autophagy machinery interconnects a wide range of cellular pathways, enhancing the spread of certain pathogens while limiting others, and has become a highly active research area over the past several years. Independent laboratories have recently reported that autophagy vesicles accumulate in hepatitis C virus (HCV) infected cells and that autophagy proteins can function as proviral factors required for HCV replication. In this review, we summarize what is currently known about the interplay between autophagy and HCV and the possible mechanisms whereby autophagy proteins might favor HCV propagation.",2011 Aug 4,"['Dreux, Marlène', 'Chisari, Francis V.']",Viruses,,,True
54283f47537cca8cedd424a4097d258dc66a9e7a,PMC,"Communicable Diseases Prioritized for Surveillance and Epidemiological Research: Results of a Standardized Prioritization Procedure in Germany, 2011",http://dx.doi.org/10.1371/journal.pone.0025691,PMC3186774,21991334,CC BY,"INTRODUCTION: To establish strategic priorities for the German national public health institute (RKI) and guide the institute's mid-term strategic decisions, we prioritized infectious pathogens in accordance with their importance for national surveillance and epidemiological research. METHODS: We used the Delphi process with internal (RKI) and external experts and a metric-consensus approach to score pathogens according to ten three-tiered criteria. Additional experts were invited to weight each criterion, leading to the calculation of a median weight by which each score was multiplied. We ranked the pathogens according to the total weighted score and divided them into four priority groups. RESULTS: 127 pathogens were scored. Eighty-six experts participated in the weighting; “Case fatality rate” was rated as the most important criterion. Twenty-six pathogens were ranked in the highest priority group; among those were pathogens with internationally recognised importance (e.g., Human Immunodeficiency Virus, Mycobacterium tuberculosis, Influenza virus, Hepatitis C virus, Neisseria meningitides), pathogens frequently causing large outbreaks (e.g., Campylobacter spp.), and nosocomial pathogens associated with antimicrobial resistance. Other pathogens in the highest priority group included Helicobacter pylori, Respiratory Syncytial Virus, Varicella zoster virus and Hantavirus. DISCUSSION: While several pathogens from the highest priority group already have a high profile in national and international health policy documents, high scores for other pathogens (e.g., Helicobacter pylori, Respiratory syncytial virus or Hantavirus) indicate a possible under-recognised importance within the current German public health framework. A process to strengthen respective surveillance systems and research has been started. The prioritization methodology has worked well; its modular structure makes it potentially useful for other settings.",2011 Oct 4,"['Balabanova, Yanina', 'Gilsdorf, Andreas', 'Buda, Silke', 'Burger, Reinhard', 'Eckmanns, Tim', 'Gärtner, Barbara', 'Groß, Uwe', 'Haas, Walter', 'Hamouda, Osamah', 'Hübner, Johannes', 'Jänisch, Thomas', 'Kist, Manfred', 'Kramer, Michael H.', 'Ledig, Thomas', 'Mielke, Martin', 'Pulz, Matthias', 'Stark, Klaus', 'Suttorp, Norbert', 'Ulbrich, Uta', 'Wichmann, Ole', 'Krause, Gérard']",PLoS One,,,True
aa92ab17aef0b2ef391bad5a3590956c72794948,PMC,Estimating Infection Attack Rates and Severity in Real Time during an Influenza Pandemic: Analysis of Serial Cross-Sectional Serologic Surveillance Data,http://dx.doi.org/10.1371/journal.pmed.1001103,PMC3186812,21990967,CC BY,"BACKGROUND: In an emerging influenza pandemic, estimating severity (the probability of a severe outcome, such as hospitalization, if infected) is a public health priority. As many influenza infections are subclinical, sero-surveillance is needed to allow reliable real-time estimates of infection attack rate (IAR) and severity. METHODS AND FINDINGS: We tested 14,766 sera collected during the first wave of the 2009 pandemic in Hong Kong using viral microneutralization. We estimated IAR and infection-hospitalization probability (IHP) from the serial cross-sectional serologic data and hospitalization data. Had our serologic data been available weekly in real time, we would have obtained reliable IHP estimates 1 wk after, 1–2 wk before, and 3 wk after epidemic peak for individuals aged 5–14 y, 15–29 y, and 30–59 y. The ratio of IAR to pre-existing seroprevalence, which decreased with age, was a major determinant for the timeliness of reliable estimates. If we began sero-surveillance 3 wk after community transmission was confirmed, with 150, 350, and 500 specimens per week for individuals aged 5–14 y, 15–19 y, and 20–29 y, respectively, we would have obtained reliable IHP estimates for these age groups 4 wk before the peak. For 30–59 y olds, even 800 specimens per week would not have generated reliable estimates until the peak because the ratio of IAR to pre-existing seroprevalence for this age group was low. The performance of serial cross-sectional sero-surveillance substantially deteriorates if test specificity is not near 100% or pre-existing seroprevalence is not near zero. These potential limitations could be mitigated by choosing a higher titer cutoff for seropositivity. If the epidemic doubling time is longer than 6 d, then serial cross-sectional sero-surveillance with 300 specimens per week would yield reliable estimates when IAR reaches around 6%–10%. CONCLUSIONS: Serial cross-sectional serologic data together with clinical surveillance data can allow reliable real-time estimates of IAR and severity in an emerging pandemic. Sero-surveillance for pandemics should be considered. Please see later in the article for the Editors' Summary",2011 Oct 4,"['Wu, Joseph T.', 'Ho, Andrew', 'Ma, Edward S. K.', 'Lee, Cheuk Kwong', 'Chu, Daniel K. W.', 'Ho, Po-Lai', 'Hung, Ivan F. N.', 'Ho, Lai Ming', 'Lin, Che Kit', 'Tsang, Thomas', 'Lo, Su-Vui', 'Lau, Yu-Lung', 'Leung, Gabriel M.', 'Cowling, Benjamin J.', 'Peiris, J. S. Malik']",PLoS Med,,,True
ae0547531bec47c718e9f48ebb2454d9fdf4e487,PMC,Changes in Population Dynamics in Mutualistic versus Pathogenic Viruses,http://dx.doi.org/10.3390/v3010012,PMC3187592,21994724,CC BY,"Although generally regarded as pathogens, viruses can also be mutualists. A number of examples of extreme mutualism (i.e., symbiogenesis) have been well studied. Other examples of mutualism are less common, but this is likely because viruses have rarely been thought of as having any beneficial effects on their hosts. The effect of mutualism on the population dynamics of viruses is a topic that has not been addressed experimentally. However, the potential for understanding mutualism and how a virus might become a mutualist may be elucidated by understanding these dynamics.",2011 Jan 17,"Roossinck, Marilyn J.",Viruses,,,True
8a1da932b899d2a04b8e8ce1ccd2ce02bc352c9e,PMC,"A Potent, Broad-Spectrum Antiviral Agent that Targets Viral Membranes",http://dx.doi.org/10.3390/v2051106,PMC3187600,21994673,CC BY,"Commentary on Wolf, M.C.; Freiberg, A.N.; Zhang, T.; Akyol-Ataman, Z.; Grock, A.; Hong, P.W.; Li, J.; Watson, N.F.; Fang, A.Q.; Aguilar, H.C.; et al. A broad-spectrum antiviral targeting entry of enveloped viruses. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 3157–3162.",2010 May 4,"['Wojcechowskyj, Jason A.', 'Doms, Robert W.']",Viruses,,,True
b6fa578aa0397c1d6e2e0340b8581eb2c318974a,PMC,Role of Cellular Lipids in Positive-Sense RNA Virus Replication Complex Assembly and Function,http://dx.doi.org/10.3390/v2051055,PMC3187604,21994671,CC BY,"Positive-sense RNA viruses are responsible for frequent and often devastating diseases in humans, animals, and plants. However, the development of effective vaccines and anti-viral therapies targeted towards these pathogens has been hindered by an incomplete understanding of the molecular mechanisms involved in viral replication. One common feature of all positive-sense RNA viruses is the manipulation of host intracellular membranes for the assembly of functional viral RNA replication complexes. This review will discuss the interplay between cellular membranes and positive-sense RNA virus replication, and will focus specifically on the potential structural and functional roles for cellular lipids in this process.",2010 Apr 29,"['Stapleford, Kenneth A.', 'Miller, David J.']",Viruses,,,True
871ebc4ba030dbc666e9520d28b5f64e7a0ebf17,PMC,Unconventional Use of LC3 by Coronaviruses through the Alleged Subversion of the ERAD Tuning Pathway,http://dx.doi.org/10.3390/v3091610,PMC3187687,21994798,CC BY,"Pathogens of bacterial and viral origin hijack pathways operating in eukaryotic cells in many ways in order to gain access into the host, to establish themselves and to eventually produce their progeny. The detailed molecular characterization of the subversion mechanisms devised by pathogens to infect host cells is crucial to generate targets for therapeutic intervention. Here we review recent data indicating that coronaviruses probably co-opt membranous carriers derived from the endoplasmic reticulum, which contain proteins that regulate disposal of misfolded polypeptides, for their replication. In addition, we also present models describing potential mechanisms that coronaviruses could employ for this hijacking.",2011 Sep 5,"['Reggiori, Fulvio', 'de Haan, Cornelis A.M.', 'Molinari, Maurizio']",Viruses,,,True
5adc6c6cf5b6d7306ed52327e9ccec7a1512f1e4,PMC,Recombination in Avian Gamma-Coronavirus Infectious Bronchitis Virus,http://dx.doi.org/10.3390/v3091777,PMC3187689,21994806,CC BY,"Recombination in the family Coronaviridae has been well documented and is thought to be a contributing factor in the emergence and evolution of different coronaviral genotypes as well as different species of coronavirus. However, there are limited data available on the frequency and extent of recombination in coronaviruses in nature and particularly for the avian gamma-coronaviruses where only recently the emergence of a turkey coronavirus has been attributed solely to recombination. In this study, the full-length genomes of eight avian gamma-coronavirus infectious bronchitis virus (IBV) isolates were sequenced and along with other full-length IBV genomes available from GenBank were analyzed for recombination. Evidence of recombination was found in every sequence analyzed and was distributed throughout the entire genome. Areas that have the highest occurrence of recombination are located in regions of the genome that code for nonstructural proteins 2, 3 and 16, and the structural spike glycoprotein. The extent of the recombination observed, suggests that this may be one of the principal mechanisms for generating genetic and antigenic diversity within IBV. These data indicate that reticulate evolutionary change due to recombination in IBV, likely plays a major role in the origin and adaptation of the virus leading to new genetic types and strains of the virus.",2011 Sep 23,"['Thor, Sharmi W.', 'Hilt, Deborah A.', 'Kissinger, Jessica C.', 'Paterson, Andrew H.', 'Jackwood, Mark W.']",Viruses,,,True
c6d8bc1c51f8962ffbeb497c413e3e5e225b9c3e,PMC,Picornavirus Subversion of the Autophagy Pathway,http://dx.doi.org/10.3390/v3091549,PMC3187694,21994795,CC BY,"While autophagy has been shown to act as an anti-viral defense, the Picornaviridae avoid and, in many cases, subvert this pathway to promote their own replication. Evidence indicates that some picornaviruses hijack autophagy in order to induce autophagosome-like membrane structures for genomic RNA replication. Expression of picornavirus proteins can specifically induce the machinery of autophagy, although the mechanisms by which the viruses employ autophagy appear to differ. Many picornaviruses up-regulate autophagy in order to promote viral replication while some members of the family also inhibit degradation by autolysosomes. Here we explore the unusual relationship of this medically important family of viruses with a degradative mechanism of innate immunity.",2011 Aug 26,"['Klein, Kathryn A.', 'Jackson, William T.']",Viruses,,,True
a6f36e3233319626ec737895c1d52dedd7aac0bf,PMC,Recombination in Eukaryotic Single Stranded DNA Viruses,http://dx.doi.org/10.3390/v3091699,PMC3187698,21994803,CC BY,"Although single stranded (ss) DNA viruses that infect humans and their domesticated animals do not generally cause major diseases, the arthropod borne ssDNA viruses of plants do, and as a result seriously constrain food production in most temperate regions of the world. Besides the well known plant and animal-infecting ssDNA viruses, it has recently become apparent through metagenomic surveys of ssDNA molecules that there also exist large numbers of other diverse ssDNA viruses within almost all terrestrial and aquatic environments. The host ranges of these viruses probably span the tree of life and they are likely to be important components of global ecosystems. Various lines of evidence suggest that a pivotal evolutionary process during the generation of this global ssDNA virus diversity has probably been genetic recombination. High rates of homologous recombination, non-homologous recombination and genome component reassortment are known to occur within and between various different ssDNA virus species and we look here at the various roles that these different types of recombination may play, both in the day-to-day biology, and in the longer term evolution, of these viruses. We specifically focus on the ecological, biochemical and selective factors underlying patterns of genetic exchange detectable amongst the ssDNA viruses and discuss how these should all be considered when assessing the adaptive value of recombination during ssDNA virus evolution.",2011 Sep 13,"['Martin, Darren P.', 'Biagini, Philippe', 'Lefeuvre, Pierre', 'Golden, Michael', 'Roumagnac, Philippe', 'Varsani, Arvind']",Viruses,,,True
32b29df5230354c35d8734b996e5e45501a5111b,PMC,A Vesicular Stomatitis Virus Replicon-Based Bioassay for the Rapid and Sensitive Determination of Multi-Species Type I Interferon,http://dx.doi.org/10.1371/journal.pone.0025858,PMC3187809,21998709,CC BY,"Type I interferons (IFN) comprise a family of cytokines that signal through a common cellular receptor to induce a plethora of genes with antiviral and other activities. Recombinant IFNs are used for the treatment of hepatitis C virus infection, multiple sclerosis, and certain malignancies. The capability of type I IFN to suppress virus replication and resultant cytopathic effects is frequently used to measure their bioactivity. However, these assays are time-consuming and require appropriate biosafety containment. In this study, an improved IFN assay is presented which is based on a recombinant vesicular stomatitis virus (VSV) replicon encoding two reporter proteins, firefly luciferase and green fluorescent protein. The vector lacks the essential envelope glycoprotein (G) gene of VSV and is propagated on a G protein-expressing transgenic cell line. Several mammalian and avian cells turned out to be susceptible to infection with the complemented replicon particles. Infected cells readily expressed the reporter proteins at high levels five hours post infection. When human fibroblasts were treated with serial dilutions of human IFN-β prior to infection, reporter expression was accordingly suppressed. This method was more sensitive and faster than a classical IFN bioassay based on VSV cytopathic effects. In addition, the antiviral activity of human IFN-λ (interleukin-29), a type III IFN, was determined on Calu-3 cells. Both IFN-β and IFN-λ were acid-stable, but only IFN-β was resistant to alkaline treatment. The antiviral activities of canine, porcine, and avian type I IFN were analysed with cell lines derived from the corresponding species. This safe bioassay will be useful for the rapid and sensitive quantification of multi-species type I IFN and potentially other antiviral cytokines.",2011 Oct 5,"['Berger Rentsch, Marianne', 'Zimmer, Gert']",PLoS One,,,True
fc5a448b2c227817cd29625972acb40e853cac89,PMC,Conceptualising the technical relationship of animal disease surveillance to intervention and mitigation as a basis for economic analysis,http://dx.doi.org/10.1186/1472-6963-11-225,PMC3189394,21929812,CC BY,"BACKGROUND: Surveillance and intervention are resource-using activities of strategies to mitigate the unwanted effects of disease. Resources are scarce, and allocating them to disease mitigation instead of other uses necessarily involves the loss of alternative sources of benefit to people. For society to obtain the maximum benefits from using resources, the gains from disease mitigation must be compared to the resource costs, guiding decisions made with the objective of achieving the optimal net outcome. DISCUSSION: Economics provides criteria to guide decisions aimed at optimising the net benefits from the use of scarce resources. Assessing the benefits of disease mitigation is no exception. However, the technical complexity of mitigation means that economic evaluation is not straightforward because of the technical relationship of surveillance to intervention. We argue that analysis of the magnitudes and distribution of benefits and costs for any given strategy, and hence the outcome in net terms, requires that mitigation is considered in three conceptually distinct stages. In Stage I, 'sustainment', the mitigation objective is to sustain a free or acceptable status by preventing an increase of a pathogen or eliminating it when it occurs. The role of surveillance is to document that the pathogen remains below a defined threshold, giving early warning of an increase in incidence or other significant changes in risk, and enabling early response. If a pathogen is not contained, the situation needs to be assessed as Stage II, 'investigation'. Here, surveillance obtains critical epidemiological information to decide on the appropriate intervention strategy to reduce or eradicate a disease in Stage III, 'implementation'. Stage III surveillance informs the choice, timing, and scale of interventions and documents the progress of interventions directed at prevalence reduction in the population. SUMMARY: This article originates from a research project to develop a conceptual framework and practical tool for the economic evaluation of surveillance. Exploring the technical relationship between mitigation as a source of economic value and surveillance and intervention as sources of economic cost is crucial. A framework linking the key technical relationships is proposed. Three conceptually distinct stages of mitigation are identified. Avian influenza, salmonella, and foot and mouth disease are presented to illustrate the framework.",2011 Sep 19,"['Häsler, Barbara', 'Howe, Keith S', 'Stärk, Katharina DC']",BMC Health Serv Res,,,True
b85bcfe513307afbac6c3bd5866dc0c0aecd28a5,PMC,"Characterization of Neutralizing Profiles in HIV-1 Infected Patients from whom the HJ16, HGN194 and HK20 mAbs were Obtained",http://dx.doi.org/10.1371/journal.pone.0025488,PMC3189917,22016769,CC BY,"Several new human monoclonal antibodies (mAbs) with a neutralizing potential across different subtypes have recently been described. Three mAbs, HJ16, HGN194 and HK20, were obtained from patients within the HIV-1 cohort of the Institute of Tropical Medicine (ITM). Our aim was to generate immunization antibodies equivalent to those seen in plasma. Here, we describe the selection and characterization of patient plasma and their mAbs, using a range of neutralization assays, including several peripheral blood mononuclear cell (PBMC) based assays and replicating primary viruses as well as cell line based assays and pseudoviruses (PV). The principal criterion for selection of patient plasma was the activity in an ‘extended incubation phase’ PBMC assay. Neutralizing Abs, derived from their memory B cells, were then selected by ELISA with envelope proteins as solid phase. MAbs were subsequently tested in a high-throughput HOS-PV assay to assess functional neutralization. The present study indicates that the strong profiles in the patients' plasma were not solely due to antibodies represented by the newly isolated mAbs. Although results from the various assays were divergent, they by and large indicate that neutralizing Abs to other epitopes of the HIV-1 envelope are present in the plasma and synergy between Abs may be important. Thus, the spectrum of the obtained mAbs does not cover the range of cross-reactivity seen in plasma in these carefully selected patients irrespective of which neutralization assay is used. Nevertheless, these mAbs are relevant for immunogen discovery because they bind to the recombinant glycoproteins to which the immune response needs to be targeted in vivo. Our observations illustrate the remaining challenges required for successful immunogen design and development.",2011 Oct 10,"['Balla-Jhagjhoorsingh, Sunita S.', 'Willems, Betty', 'Heyndrickx, Liesbeth', 'Heyndrickx, Leo', 'Vereecken, Katleen', 'Janssens, Wouter', 'Seaman, Michael S.', 'Corti, Davide', 'Lanzavecchia, Antonio', 'Davis, David', 'Vanham, Guido']",PLoS One,,,True
ca866226d436ba4c39fe854f9cc568f08638868d,PMC,EBV-gp350 Confers B-Cell Tropism to Tailored Exosomes and Is a Neo-Antigen in Normal and Malignant B Cells—A New Option for the Treatment of B-CLL,http://dx.doi.org/10.1371/journal.pone.0025294,PMC3189918,22022385,CC BY,"gp350, the major envelope protein of Epstein-Barr-Virus, confers B-cell tropism to the virus by interacting with the B lineage marker CD21. Here we utilize gp350 to generate tailored exosomes with an identical tropism. These exosomes can be used for the targeted co-transfer of functional proteins to normal and malignant human B cells. We demonstrate here the co-transfer of functional CD154 protein on tailored gp350+ exosomes to malignant B blasts from patients with B chronic lymphocytic leukemia (B-CLL), rendering B blasts immunogenic to tumor-reactive autologous T cells. Intriguingly, engulfment of gp350+ exosomes by B-CLL cells and presentation of gp350-derived peptides also re-stimulated EBV-specific T cells and redirected the strong antiviral cellular immune response in patients to leukemic B cells. In essence, we show that gp350 alone confers B-cell tropism to exosomes and that these exosomes can be further engineered to simultaneously trigger virus- and tumor-specific immune responses. The simultaneous exploitation of gp350 as a tropism molecule for tailored exosomes and as a neo-antigen in malignant B cells provides a novel attractive strategy for immunotherapy of B-CLL and other B-cell malignancies.",2011 Oct 10,"['Ruiss, Romana', 'Jochum, Simon', 'Mocikat, Ralph', 'Hammerschmidt, Wolfgang', 'Zeidler, Reinhard']",PLoS One,,,True
f659c70f5c28f2b2694bc76b0a57b47d8d6362d5,PMC,Viral Double-Strand RNA-Binding Proteins Can Enhance Innate Immune Signaling by Toll-Like Receptor 3,http://dx.doi.org/10.1371/journal.pone.0025837,PMC3189932,22016778,CC BY,"Toll-like Receptor 3 (TLR3) detects double-stranded (ds) RNAs to activate innate immune responses. While poly(I:C) is an excellent agonist for TLR3 in several cell lines and in human peripheral blood mononuclear cells, viral dsRNAs tend to be poor agonists, leading to the hypothesis that additional factor(s) are likely required to allow TLR3 to respond to viral dsRNAs. TLR3 signaling was examined in a lung epithelial cell line by quantifying cytokine production and in human embryonic kidney cells by quantifying luciferase reporter levels. Recombinant 1b hepatitis C virus polymerase was found to enhance TLR3 signaling in the lung epithelial BEAS-2B cells when added to the media along with either poly(I:C) or viral dsRNAs. The polymerase from the genotype 2a JFH-1 HCV was a poor enhancer of TLR3 signaling until it was mutated to favor a conformation that could bind better to a partially duplexed RNA. The 1b polymerase also co-localizes with TLR3 in endosomes. RNA-binding capsid proteins (CPs) from two positive-strand RNA viruses and the hepadenavirus hepatitis B virus (HBV) were also potent enhancers of TLR3 signaling by poly(I:C) or viral dsRNAs. A truncated version of the HBV CP that lacked an arginine-rich RNA-binding domain was unable to enhance TLR3 signaling. These results demonstrate that several viral RNA-binding proteins can enhance the dsRNA-dependent innate immune response initiated by TLR3.",2011 Oct 10,"['Lai, Yvonne', 'Yi, Guanghui', 'Chen, Alice', 'Bhardwaj, Kanchan', 'Tragesser, Brady J.', 'Rodrigo A. Valverde,', 'Zlotnick, Adam', 'Mukhopadhyay, Suchetana', 'Ranjith-Kumar, C. T.', 'Kao, C. Cheng']",PLoS One,,,True
5f36e6c3da64e8d95c81d9c63ad4909144f9191c,PMC,Specific Viruses Detected in Nigerian Children in Association with Acute Respiratory Disease,http://dx.doi.org/10.1155/2011/690286,PMC3191740,22007241,CC BY,"Occurrence of different viruses in acute respiratory tract infections of Nigerian children was examined. Respiratory swabs were collected from 246 children referred to hospital clinics because of acute respiratory symptoms from February through May 2009. Validated real-time RT-PCR techniques revealed nucleic acids of at least one virus group in 189 specimens (77%). Human rhinoviruses and parainfluenza viruses were present each in one third of the children. Adenoviruses, enteroviruses, human metapneumovirus, human bocavirus, and influenza C virus were also relatively common. Possibly due to their seasonal occurrence, influenza A and B virus, and respiratory syncytial virus were detected rarely. We conclude that all major groups of respiratory tract viruses are causing illness in Nigerian children.",2011 Oct 11,"['Akinloye, Oluwabukola M.', 'Rönkkö, Esa', 'Savolainen-Kopra, Carita', 'Ziegler, Thedi', 'Iwalokun, Bamidele A.', 'Deji-Agboola, Mope A.', 'Oluwadun, Afolabi', 'Roivainen, Merja', 'Adu, Festus D.', 'Hovi, Tapani']",J Trop Med,,,True
15f2b1915443fff0466f0dd89c7c0ab6761833b4,PMC,Detection of a Fourth Orbivirus Non-Structural Protein,http://dx.doi.org/10.1371/journal.pone.0025697,PMC3192121,22022432,CC BY,"The genus Orbivirus includes both insect and tick-borne viruses. The orbivirus genome, composed of 10 segments of dsRNA, encodes 7 structural proteins (VP1–VP7) and 3 non-structural proteins (NS1–NS3). An open reading frame (ORF) that spans almost the entire length of genome segment-9 (Seg-9) encodes VP6 (the viral helicase). However, bioinformatic analysis recently identified an overlapping ORF (ORFX) in Seg-9. We show that ORFX encodes a new non-structural protein, identified here as NS4. Western blotting and confocal fluorescence microscopy, using antibodies raised against recombinant NS4 from Bluetongue virus (BTV, which is insect-borne), or Great Island virus (GIV, which is tick-borne), demonstrate that these proteins are synthesised in BTV or GIV infected mammalian cells, respectively. BTV NS4 is also expressed in Culicoides insect cells. NS4 forms aggregates throughout the cytoplasm as well as in the nucleus, consistent with identification of nuclear localisation signals within the NS4 sequence. Bioinformatic analyses indicate that NS4 contains coiled-coils, is related to proteins that bind nucleic acids, or are associated with membranes and shows similarities to nucleolar protein UTP20 (a processome subunit). Recombinant NS4 of GIV protects dsRNA from degradation by endoribonucleases of the RNAse III family, indicating that it interacts with dsRNA. However, BTV NS4, which is only half the putative size of the GIV NS4, did not protect dsRNA from RNAse III cleavage. NS4 of both GIV and BTV protect DNA from degradation by DNAse. NS4 was found to associate with lipid droplets in cells infected with BTV or GIV or transfected with a plasmid expressing NS4.",2011 Oct 12,"['Belhouchet, Mourad', 'Mohd Jaafar, Fauziah', 'Firth, Andrew E.', 'Grimes, Jonathan M.', 'Mertens, Peter P. C.', 'Attoui, Houssam']",PLoS One,,,True
3ec7aa1d4381bbaa7f5fa69fa8eb7cc1d90a39f1,PMC,Geographic Distribution and Risk Factors of the Initial Adult Hospitalized Cases of 2009 Pandemic Influenza A (H1N1) Virus Infection in Mainland China,http://dx.doi.org/10.1371/journal.pone.0025934,PMC3192122,22022474,CC BY,"BACKGROUND: As of 31(st) March 2010, more than 127,000 confirmed cases of 2009 pandemic influenza A (H1N1), including 800 deaths, were reported in mainland China. The distribution and characteristics of the confirmed cases in the initial phase of this pandemic in this country are largely unknown. The present study aimed to characterize the geographic distribution and patient characteristics of H1N1 infection in the 2009 pandemic as well as to identify potential risk factors associated with adverse patient outcome in China, through retrospective analyses of 885 hospitalized cases with confirmed H1N1 infection. METHODOLOGY/PRINCIPAL FINDINGS: The proportional hazards model was employed to detect risk factors for adverse outcome; the geo-statistical maps were used to characterize the distribution of all 2668 confirmed H1N1 patients throughout mainland China. The number of new cases increased slowly in May, 2009, but rapidly between June and August of the year. Confirmed cases were reported in 26 provinces; Beijing, Guangdong, Shanghai, Zhejiang and Fujian were the top five regions of the incidence of the virus infection. After being adjusted for gender, age, chronic pulmonary disease and other general symptoms, delay for more than two days before hospital admission (HR: 0.6; 95%CI: 0.5–0.7) and delayed onset of the H1N1-specific respiratory symptoms (HR: 0.3; 95%CI: 0.2–0.4) were associated with adverse patient outcome. CONCLUSIONS/SIGNIFICANCE: The 2009 pandemic influenza A affected east and southeast coastal provinces and most populous cities more severely than other regions in mainland China due to higher risk of high level traffic-, high population density-, and high population mobility-associated H1N1 transmission.The clinical symptoms were mild in the initial phase of infection. Delayed hospital admission and delayed appearance of respiratory symptoms were among the major risk factors for poor patient outcome. These findings may have significant implications in the future pandemic preparedness and response.",2011 Oct 12,"['Liu, Yunning', 'Wang, Wei', 'Li, Xia', 'Wang, Hong', 'Luo, Yanxia', 'Wu, Lijuan', 'Guo, Xiuhua']",PLoS One,,,True
121f06c44cde088607a6f4d16098eb6101513c01,PMC,Pulsed electromagnetic fields stimulation prevents steroid-induced osteonecrosis in rats,http://dx.doi.org/10.1186/1471-2474-12-215,PMC3192716,21958301,CC BY,"BACKGROUND: Pulsed electromagnetic fields (PEMF) stimulation has been used successfully to treat nonunion fractures and femoral head osteonecrosis, but relatively little is known about its effects on preventing steroid-induced osteonecrosis. The purpose of the study was to investigate the effects of PEMF stimulation on the prevention of steroid-induced osteonecrosis in rats and explore the underlying mechanisms. METHODS: Seventy-two male adult Wistar rats were divided into three groups and treated as follows. (1) PEMF stimulation group (PEMF group, n = 24): intravenously injected with lipopolysaccharide (LPS, 10 μg/kg) on day 0 and intramuscularly injected with methylprednisolone acetate (MPSL, 20 mg/kg) on days 1, 2 and 3, then subjected to PEMF stimulation 4 h per day for 1 to 8 weeks. (2) Methylprednisolone-treated group (MPSL group, n = 24): injected the same dose of LPS and MPSL as the PEMF group but without exposure to PEMF. (3) Control group (PS group, n = 24): injected 0.9% saline in the same mode at the same time points. The incidence of osteonecrosis, serum lipid levels and the mRNA and protein expression of transforming growth factor β1 (TGF-β1) in the proximal femur were measured 1, 2, 4 and 8 weeks after the last MPSL (or saline) injection. RESULTS: The incidence of osteonecrosis in the PEMF group (29%) was significantly lower than that observed in the MPSL group (75%), while no osteonecrosis was observed in the PS group. The serum lipid levels were significantly lower in the PEMF and PS groups than in the MPSL group. Compared with the MPSL and PS groups, the mRNA expression of TGF-β1 increased, reaching a peak 1 week after PEMF treatment, and remained high for 4 weeks, then declined at 8 weeks, whereas the protein expression of TGF-β1 increased, reaching a peak at 2 weeks after PEMF treatment, and remained high for 8 weeks. CONCLUSIONS: PEMF stimulation can prevent steroid-induced osteonecrosis in rats, and the underlying mechanisms involve decreased serum lipid levels and increased expression of TGF-β1.",2011 Sep 29,"['Ding, Shuai', 'Peng, Hao', 'Fang, Hong-Song', 'Zhou, Jian-Lin', 'Wang, Zhe']",BMC Musculoskelet Disord,,,True
eafa4d1bd1e62bf88d6d2813002cfe6c33be8b95,PMC,Investigation of a Potential Zoonotic Transmission of Orthoreovirus Associated with Acute Influenza-Like Illness in an Adult Patient,http://dx.doi.org/10.1371/journal.pone.0025434,PMC3192755,22022394,CC BY,"Bats are increasingly being recognized as important reservoir hosts for a large number of viruses, some of them can be highly virulent when they infect human and livestock animals. Among the new bat zoonotic viruses discovered in recent years, several reoviruses (respiratory enteric orphan viruses) were found to be able to cause acute respiratory infections in humans, which included Melaka and Kampar viruses discovered in Malaysia, all of them belong to the genus Orthoreovirus, family Reoviridae. In this report, we describe the isolation of a highly related virus from an adult patient who suffered acute respiratory illness in Malaysia. Although there was no direct evidence of bat origin, epidemiological study indicated the potential exposure of the patient to bats before the onset of disease. The current study further demonstrates that spillover events of different strains of related orthoreoviruses from bats to humans are occurring on a regular basis, which calls for more intensive and systematic surveillances to fully assess the true public health impact of these newly discovered bat-borne zoonotic reoviruses.",2011 Oct 13,"['Chua, Kaw Bing', 'Voon, Kenny', 'Yu, Meng', 'Keniscope, Canady', 'Abdul Rasid, Kasri', 'Wang, Lin-Fa']",PLoS One,,,True
4296edbb527d1e55ad2079c76f619659e0b5720d,PMC,Therapy and Long-Term Prophylaxis of Vaccinia Virus Respiratory Infections in Mice with an Adenovirus-Vectored Interferon Alpha (mDEF201),http://dx.doi.org/10.1371/journal.pone.0026330,PMC3192798,22022603,CC BY,"An adenovirus 5 vector encoding for mouse interferon alpha, subtype 5 (mDEF201) was evaluated for efficacy against lethal vaccinia virus (WR strain) respiratory infections in mice. mDEF201 was administered as a single intranasal treatment either prophylactically or therapeutically at doses of 10(6) to 10(8) plaque forming units/mouse. When the prophylactic treatment was given at 56 days prior to infection, it protected 90% of animals from death (100% protection for treatments given between 1–49 days pre-infection), with minimal weight loss occurring during infection. Surviving animals re-challenged with virus 22 days after the primary infection were protected from death, indicating that mDEF201 did not compromise the immune response against the initial infection. Post-exposure therapy was given between 6–24 h after vaccinia virus exposure and protection was afforded by a 10(8) dose of mDEF201 given at 24 h, whereas a 10(7) dose was effective up to 12 h. Comparisons were made of the ability of mDEF201, given either 28 or 1 day prior to infection, to inhibit tissue virus titers and lung infection parameters. Lung, liver, and spleen virus titers were inhibited to nearly the same extent by either treatment, as were lung weights and lung hemorrhage scores (indicators of pneumonitis). Lung virus titers were significantly (>100-fold) lower than in the placebo group, and the other infection parameters in mDEF201 treated mice were nearly at baseline. In contrast, viral titers and lung infection parameters were high in the placebo group on day 5 of the infection. These results demonstrate the long-acting prophylactic and treatment capacity of mDEF201 to combat vaccinia virus infections.",2011 Oct 13,"['Smee, Donald F.', 'Wong, Min-Hui', 'Russell, Andrew', 'Ennis, Jane', 'Turner, Jeffrey D.']",PLoS One,,,True
4ec19e6a2799bf2bebe635732de198d04ddedf64,PMC,Biochemical and Structural Insights into the Mechanisms of SARS Coronavirus RNA Ribose 2′-O-Methylation by nsp16/nsp10 Protein Complex,http://dx.doi.org/10.1371/journal.ppat.1002294,PMC3192843,22022266,CC BY,"The 5′-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5′-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2′-O positions, catalyzed by nsp14 N7-MTase and nsp16 2′-O-MTase, respectively. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2′-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1∶1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs.",2011 Oct 13,"['Chen, Yu', 'Su, Ceyang', 'Ke, Min', 'Jin, Xu', 'Xu, Lirong', 'Zhang, Zhou', 'Wu, Andong', 'Sun, Ying', 'Yang, Zhouning', 'Tien, Po', 'Ahola, Tero', 'Liang, Yi', 'Liu, Xinqi', 'Guo, Deyin']",PLoS Pathog,,,True
2c0c7b9bdc81461fbf533ae6b89fd78326651306,PMC,Improved vaccine protection against retrovirus infection after co-administration of adenoviral vectors encoding viral antigens and type I interferon subtypes,http://dx.doi.org/10.1186/1742-4690-8-75,PMC3193818,21943056,CC BY,"BACKGROUND: Type I interferons (IFNs) exhibit direct antiviral effects, but also distinct immunomodulatory properties. In this study, we analyzed type I IFN subtypes for their effect on prophylactic adenovirus-based anti-retroviral vaccination of mice against Friend retrovirus (FV) or HIV. RESULTS: Mice were vaccinated with adenoviral vectors encoding FV Env and Gag proteins alone or in combination with vectors encoding IFNα1, IFNα2, IFNα4, IFNα5, IFNα6, IFNα9 or IFNβ. Only the co-administration of adenoviral vectors encoding IFNα2, IFNα4, IFNα6 and IFNα9 resulted in strongly improved immune protection of vaccinated mice from subsequent FV challenge infection with high control over FV-induced splenomegaly and reduced viral loads. The level of protection correlated with augmented virus-specific CD4(+ )T cell responses and enhanced antibody titers. Similar results were obtained when mice were vaccinated against HIV with adenoviral vectors encoding HIV Env and Gag-Pol in combination with various type I IFN encoding vectors. Here mainly CD4(+ )T cell responses were enhanced by IFNα subtypes. CONCLUSIONS: Our results indicate that certain IFNα subtypes have the potential to improve the protective effect of adenovirus-based vaccines against retroviruses. This correlated with augmented virus-specific CD4(+ )T cell and antibody responses. Thus, co-expression of select type I IFNs may be a valuable tool for the development of anti-retroviral vaccines.",2011 Sep 26,"['Bayer, Wibke', 'Lietz, Ruth', 'Ontikatze, Teona', 'Johrden, Lena', 'Tenbusch, Matthias', 'Nabi, Ghulam', 'Schimmer, Simone', 'Groitl, Peter', 'Wolf, Hans', 'Berry, Cassandra M', 'Überla, Klaus', 'Dittmer, Ulf', 'Wildner, Oliver']",Retrovirology,,,True
e3d75d7baf118918395a6950b724215ec2c8023c,PMC,Identification and Typing of Human Enterovirus: A Genomic Barcode Approach,http://dx.doi.org/10.1371/journal.pone.0026296,PMC3194813,22022592,CC BY,"Identification and typing of human enterovirus (HEVs) are important to pathogen detection and therapy. Previous phylogeny-based typing methods are mainly based on multiple sequence alignments of specific genes in the HEVs, but the results are not stable with respect to different choices of genes. Here we report a novel method for identification and typing of HEVs based on information derived from their whole genomes. Specifically, we calculate the k-mer based barcode image for each genome, HEV or other human viruses, for a fixed k, 1<k<7, where a genome barcode is defined in terms of the k-mer frequency distribution across the whole genome for all combinations of k-mers. A phylogenetic tree is constructed using a barcode-based distance and a neighbor-joining method among a set of 443 representative non-HEV human viruses and 395 HEV sequences. The tree shows a clear separation of the HEV viruses from all the non-HEV viruses with 100% accuracy and a separation of the HEVs into four distinct clads with 93.4% consistency with a multiple sequence alignment-based phylogeny. Our detailed analyses of the HEVs having different typing results by the two methods indicate that our results are in better agreement with known information about the HEVs.",2011 Oct 14,"['Wei, Chengguo', 'Wang, Guoqing', 'Chen, Xin', 'Huang, Honglan', 'Liu, Bin', 'Xu, Ying', 'Li, Fan']",PLoS One,,,True
84bf3b3e1716be122763fef2463f88970a8306d9,PMC,Ebola Virion Attachment and Entry into Human Macrophages Profoundly Effects Early Cellular Gene Expression,http://dx.doi.org/10.1371/journal.pntd.0001359,PMC3196478,22028943,CC0,"Zaire ebolavirus (ZEBOV) infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention. Gene expression profiles of primary human macrophages exposed to ZEBOV were determined using DNA microarrays and quantitative PCR to gain insight into the cellular response immediately after cell entry. Significant changes in mRNA concentrations encoding for 88 cellular proteins were observed. Most of these proteins have not yet been implicated in ZEBOV infection. Some, however, are inflammatory mediators known to be elevated during the acute phase of disease in the blood of ZEBOV-infected humans. Interestingly, the cellular response occurred within the first hour of Ebola virion exposure, i.e. prior to virus gene expression. This observation supports the hypothesis that virion binding or entry mediated by the spike glycoprotein (GP(1,2)) is the primary stimulus for an initial response. Indeed, ZEBOV virions, LPS, and virus-like particles consisting of only the ZEBOV matrix protein VP40 and GP(1,2) (VLP(VP40-GP)) triggered comparable responses in macrophages, including pro-inflammatory and pro-apoptotic signals. In contrast, VLP(VP40) (particles lacking GP(1,2)) caused an aberrant response. This suggests that GP(1,2) binding to macrophages plays an important role in the immediate cellular response.",2011 Oct 18,"['Wahl-Jensen, Victoria', 'Kurz, Sabine', 'Feldmann, Friedericke', 'Buehler, Lukas K.', 'Kindrachuk, Jason', 'DeFilippis, Victor', 'da Silva Correia, Jean', 'Früh, Klaus', 'Kuhn, Jens H.', 'Burton, Dennis R.', 'Feldmann, Heinz']",PLoS Negl Trop Dis,,,True
4ae484254680cec3d9d6f6d55bfd97bd90877445,PMC,Orthoretroviral-like prototype foamy virus gag-pol expression is compatible with viral replication,http://dx.doi.org/10.1186/1742-4690-8-66,PMC3196705,21843316,CC BY,"BACKGROUND: Foamy viruses (FVs) unlike orthoretroviruses express Pol as a separate precursor protein and not as a Gag-Pol fusion protein. A unique packaging strategy, involving recognition of briding viral RNA by both Pol precursor and Gag as well as potential Gag-Pol protein interactions, ensures Pol particle encapsidation. RESULTS: Several Prototype FV (PFV) Gag-Pol fusion protein constructs were generated to examine whether PFV replication is compatible with an orthoretroviral-like Pol expression. During their analysis, non-particle-associated secreted Pol precursor protein was discovered in extracellular wild type PFV particle preparations of different origin, copurifying in simple virion enrichment protocols. Different analysis methods suggest that extracellular wild type PFV particles contain predominantly mature p85(PR-RT )and p40(IN )Pol subunits. Characterization of various PFV Gag-Pol fusion constructs revealed that PFV Pol expression in an orthoretroviral manner is compatible with PFV replication as long as a proteolytic processing between Gag and Pol proteins is possible. PFV Gag-Pol translation by a HIV-1 like ribosomal frameshift signal resulted in production of replication-competent virions, although cell- and particle-associated Pol levels were reduced in comparison to wild type. In-frame fusion of PFV Gag and Pol ORFs led to increased cellular Pol levels, but particle incorporation was only marginally elevated. Unlike that reported for similar orthoretroviral constructs, a full-length in-frame PFV Gag-Pol fusion construct showed wildtype-like particle release and infectivity characteristics. In contrast, in-frame PFV Gag-Pol fusion with C-terminal Gag ORF truncations or non-removable Gag peptide addition to Pol displayed wildtype particle release, but reduced particle infectivity. PFV Gag-Pol precursor fusion proteins with inactivated protease were highly deficient in regular particle release, although coexpression of p71(Gag )resulted in a significant copackaging of these proteins. CONCLUSIONS: Non-particle associated PFV Pol appears to be naturally released from infected cells by a yet unknown mechanism. The absence of particle-associated Pol precursor suggests its rapid processing upon particle incorporation. Analysis of different PFV Gag-Pol fusion constructs demonstrates that orthoretroviral-like Pol expression is compatible with FV replication in principal as long as fusion protein processing is possible. Furthermore, unlike orthoretroviruses, PFV particle release and infectivity tolerate larger differences in relative cellular Gag/Pol levels.",2011 Aug 15,"['Swiersy, Anka', 'Wiek, Constanze', 'Reh, Juliane', 'Zentgraf, Hanswalter', 'Lindemann, Dirk']",Retrovirology,,,True
c16b3804d97765832da8ea7579a114e98844c0ae,PMC,Screening of Feral and Wood Pigeons for Viruses Harbouring a Conserved Mobile Viral Element: Characterization of Novel Astroviruses and Picornaviruses,http://dx.doi.org/10.1371/journal.pone.0025964,PMC3197151,22043297,CC BY,"A highly conserved RNA-motif of yet unknown function, called stem-loop-2-like motif (s2m), has been identified in the 3′ end of the genomes of viruses belonging to different RNA virus families which infect a broad range of mammal and bird species, including Astroviridae, Picornaviridae, Coronaviridae and Caliciviridae. Since s2m is such an extremely conserved motif, it is an ideal target for screening for viruses harbouring it. In this study, we have detected and characterized novel viruses harbouring this motif in pigeons by using a s2m-specific amplification. 84% and 67% of the samples from feral pigeons and wood pigeons, respectively, were found to contain a virus harbouring s2m. Four novel viruses were identified and characterized. Two of the new viruses belong to the genus Avastrovirus in the Astroviridae family. We propose two novel species to be included in this genus, Feral pigeon astrovirus and Wood pigeon astrovirus. Two other novel viruses, Pigeon picornavirus A and Pigeon picornavirus B, belong to the Picornaviridae family, presumably to the genus Sapelovirus. Both of the novel picornaviruses harboured two adjacent s2m, called (s2m)(2), suggesting a possible increased functional effect of s2m when present in two copies.",2011 Oct 17,"['Kofstad, Tone', 'Jonassen, Christine M.']",PLoS One,,,True
ac0ed4e3ae92a0e194ea6808c289a0b6224ea054,PMC,Evaluating the Combined Effectiveness of Influenza Control Strategies and Human Preventive Behavior,http://dx.doi.org/10.1371/journal.pone.0024706,PMC3197180,22043275,CC BY,"Control strategies enforced by health agencies are a major type of practice to contain influenza outbreaks. Another type of practice is the voluntary preventive behavior of individuals, such as receiving vaccination, taking antiviral drugs, and wearing face masks. These two types of practices take effects concurrently in influenza containment, but little attention has been paid to their combined effectiveness. This article estimates this combined effectiveness using established simulation models in the urbanized area of Buffalo, NY, USA. Three control strategies are investigated, including: Targeted Antiviral Prophylaxis (TAP), workplace/school closure, community travel restriction, as well as the combination of the three. All control strategies are simulated with and without regard to individual preventive behavior, and the resulting effectiveness are compared. The simulation outcomes suggest that weaker control strategies could suffice to contain influenza epidemics, because individuals voluntarily adopt preventive behavior, rendering these weaker strategies more effective than would otherwise have been expected. The preventive behavior of individuals could save medical resources for control strategies and avoid unnecessary socio-economic interruptions. This research adds a human behavioral dimension into the simulation of control strategies and offers new insights into disease containment. Health policy makers are recommended to review current control strategies and comprehend preventive behavior patterns of local populations before making decisions on influenza containment.",2011 Oct 17,"Mao, Liang",PLoS One,,,True
c9b6f3ff358477fe654fa5e92b3fb85ebd3fb8a5,PMC,ISG15 Is Critical in the Control of Chikungunya Virus Infection Independent of UbE1L Mediated Conjugation,http://dx.doi.org/10.1371/journal.ppat.1002322,PMC3197620,22028657,CC BY,"Chikungunya virus (CHIKV) is a re-emerging alphavirus that has caused significant disease in the Indian Ocean region since 2005. During this outbreak, in addition to fever, rash and arthritis, severe cases of CHIKV infection have been observed in infants. Challenging the notion that the innate immune response in infants is immature or defective, we demonstrate that both human infants and neonatal mice generate a robust type I interferon (IFN) response during CHIKV infection that contributes to, but is insufficient for, the complete control of infection. To characterize the mechanism by which type I IFNs control CHIKV infection, we evaluated the role of ISG15 and defined it as a central player in the host response, as neonatal mice lacking ISG15 were profoundly susceptible to CHIKV infection. Surprisingly, UbE1L(−/−) mice, which lack the ISG15 E1 enzyme and therefore are unable to form ISG15 conjugates, displayed no increase in lethality following CHIKV infection, thus pointing to a non-classical role for ISG15. No differences in viral loads were observed between wild-type (WT) and ISG15(−/−) mice, however, a dramatic increase in proinflammatory cytokines and chemokines was observed in ISG15(−/−) mice, suggesting that the innate immune response to CHIKV contributes to their lethality. This study provides new insight into the control of CHIKV infection, and establishes a new model for how ISG15 functions as an immunomodulatory molecule in the blunting of potentially pathologic levels of innate effector molecules during the host response to viral infection.",2011 Oct 20,"['Werneke, Scott W.', 'Schilte, Clementine', 'Rohatgi, Anjali', 'Monte, Kristen J.', 'Michault, Alain', 'Arenzana-Seisdedos, Fernando', 'Vanlandingham, Dana L.', 'Higgs, Stephen', 'Fontanet, Arnaud', 'Albert, Matthew L.', 'Lenschow, Deborah J.']",PLoS Pathog,,,True
f93269b90d3654488b158876258d42402d64afb3,PMC,Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Regulates Cell Stress Response and Apoptosis,http://dx.doi.org/10.1371/journal.ppat.1002315,PMC3197621,22028656,CC BY,"Severe acute respiratory syndrome virus (SARS-CoV) that lacks the envelope (E) gene (rSARS-CoV-ΔE) is attenuated in vivo. To identify factors that contribute to rSARS-CoV-ΔE attenuation, gene expression in cells infected by SARS-CoV with or without E gene was compared. Twenty-five stress response genes were preferentially upregulated during infection in the absence of the E gene. In addition, genes involved in signal transduction, transcription, cell metabolism, immunoregulation, inflammation, apoptosis and cell cycle and differentiation were differentially regulated in cells infected with rSARS-CoV with or without the E gene. Administration of E protein in trans reduced the stress response in cells infected with rSARS-CoV-ΔE or with respiratory syncytial virus, or treated with drugs, such as tunicamycin and thapsigargin that elicit cell stress by different mechanisms. In addition, SARS-CoV E protein down-regulated the signaling pathway inositol-requiring enzyme 1 (IRE-1) of the unfolded protein response, but not the PKR-like ER kinase (PERK) or activating transcription factor 6 (ATF-6) pathways, and reduced cell apoptosis. Overall, the activation of the IRE-1 pathway was not able to restore cell homeostasis, and apoptosis was induced probably as a measure to protect the host by limiting virus production and dissemination. The expression of proinflammatory cytokines was reduced in rSARS-CoV-ΔE-infected cells compared to rSARS-CoV-infected cells, suggesting that the increase in stress responses and the reduction of inflammation in the absence of the E gene contributed to the attenuation of rSARS-CoV-ΔE.",2011 Oct 20,"['DeDiego, Marta L.', 'Nieto-Torres, Jose L.', 'Jiménez-Guardeño, Jose M.', 'Regla-Nava, Jose A.', 'Álvarez, Enrique', 'Oliveros, Juan Carlos', 'Zhao, Jincun', 'Fett, Craig', 'Perlman, Stanley', 'Enjuanes, Luis']",PLoS Pathog,,,True
7a5e362c102b0d9d73857a7e10df920d3a5e6334,PMC,"FilmArray, an Automated Nested Multiplex PCR System for Multi-Pathogen Detection: Development and Application to Respiratory Tract Infection",http://dx.doi.org/10.1371/journal.pone.0026047,PMC3198457,22039434,CC BY,"The ideal clinical diagnostic system should deliver rapid, sensitive, specific and reproducible results while minimizing the requirements for specialized laboratory facilities and skilled technicians. We describe an integrated diagnostic platform, the “FilmArray”, which fully automates the detection and identification of multiple organisms from a single sample in about one hour. An unprocessed biologic/clinical sample is subjected to nucleic acid purification, reverse transcription, a high-order nested multiplex polymerase chain reaction and amplicon melt curve analysis. Biochemical reactions are enclosed in a disposable pouch, minimizing the PCR contamination risk. FilmArray has the potential to detect greater than 100 different nucleic acid targets at one time. These features make the system well-suited for molecular detection of infectious agents. Validation of the FilmArray technology was achieved through development of a panel of assays capable of identifying 21 common viral and bacterial respiratory pathogens. Initial testing of the system using both cultured organisms and clinical nasal aspirates obtained from children demonstrated an analytical and clinical sensitivity and specificity comparable to existing diagnostic platforms. We demonstrate that automated identification of pathogens from their corresponding target amplicon(s) can be accomplished by analysis of the DNA melting curve of the amplicon.",2011 Oct 19,"['Poritz, Mark A.', 'Blaschke, Anne J.', 'Byington, Carrie L.', 'Meyers, Lindsay', 'Nilsson, Kody', 'Jones, David E.', 'Thatcher, Stephanie A.', 'Robbins, Thomas', 'Lingenfelter, Beth', 'Amiott, Elizabeth', 'Herbener, Amy', 'Daly, Judy', 'Dobrowolski, Steven F.', 'Teng, David H. -F.', 'Ririe, Kirk M.']",PLoS One,,,True
f472fa905ba1adcbb2fb5ebc78ce1efdae91eaa8,PMC,Public health and medical care for the world's factory: China's Pearl River Delta Region,http://dx.doi.org/10.1186/1741-7015-9-110,PMC3198886,21968214,CC BY,"While the growth of urbanization, worldwide, has improved the lives of migrants from the hinterland, it also raises health risks related to population density, concentrated poverty and the transmission of infectious disease. Will megacity regions evolve into socially infected breeding grounds for the rapid transmission of disease, or can they become critical spatial entities for the protection and promotion of population health? We address this question for the Pearl River Delta Region (PRD) based on recent data from Chinese sources, and on the experience of how New York, Greater London, Tokyo and Paris have grappled with the challenges of protecting population health and providing their populations with access to health care services. In some respects, there are some important lessons from comparative experience for PRD, notably the importance of covering the entire population for health care services and targeting special programs for those at highest risk for disease. In other respects, PRD's growth rate and sheer scale make it a unique megacity region that already faces new challenges and will require new solutions.",2011 Oct 4,"['Fabre, Guilhem', 'Rodwin, Victor G']",BMC Med,,,True
b9ac24a16dd729a1db737ead634eaa577b00febd,PMC,A Chinese Herbal Formula to Improve General Psychological Status in Posttraumatic Stress Disorder: A Randomized Placebo-Controlled Trial on Sichuan Earthquake Survivors,http://dx.doi.org/10.1155/2012/691258,PMC3199055,22028733,CC BY,"Introduction. Posttraumatic stress disorder (PTSD) is accompanied by poor general psychological status (GPS). In the present study, we investigated the effects of a Chinese herbal formula on GPS in earthquake survivors with PTSD. Methods. A randomized, double-blind, placebo-controlled trial compared a Chinese herbal formula, Xiao-Tan-Jie-Yu-Fang (XTJYF), to placebo in 2008 Sichuan earthquake survivors with PTSD. Patients were randomized into XTJYF (n = 123) and placebo (n = 122) groups. Baseline-to-end-point score changes in the three global indices of the Symptom Checklist-90-Revised (SCL-90-R) and rates of response in the SCL global severity index (GSI) were the primary endpoints. A subanalysis of the nine SCL factors and the sleep quality score were secondary endpoints. Results and Discussion. Compared to placebo, the XTJYF group was significantly improved in all three SCL global indices (P = 0.001~0.028). More patients in the XTJYF group reported “much improved” than the placebo group (P = 0.001). The XTJYF group performed significantly better than control in five out of nine SCL factors (somatization, obsessive-compulsive behavior, depression, anxiety, and hostility (P = 0.001~0.036)), and in sleep quality score (P < 0.001). XTJYF produced no serious adverse events. These findings suggest that XTJYF may be an effective and safe treatment option for improving GPS in patients with PTSD.",2012 Oct 19,"['Meng, Xian-Ze', 'Wu, Feng', 'Wei, Pin-Kang', 'Xiu, Li-Juan', 'Shi, Jun', 'Pang, Bin', 'Sun, Da-Zhi', 'Qin, Zhi-Feng', 'Huang, Yi', 'Lao, Lixing']",Evid Based Complement Alternat Med,,,True
4c5eab753837b6723778e80b1d37a32bee2b4375,PMC,Neuropathogenesis of a highly pathogenic avian influenza virus (H7N1) in experimentally infected chickens,http://dx.doi.org/10.1186/1297-9716-42-106,PMC3199250,21982125,CC BY,"In order to understand the mechanism of neuroinvasion of a highly pathogenic avian influenza virus (HPAIV) into the central nervous system (CNS) of chickens, specific pathogen free chickens were inoculated with a H7N1 HPAIV. Blood, cerebrospinal fluid (CSF), nasal cavity and brain tissue samples were obtained from 1 to 4 days post-inoculation (dpi) of infected and control chickens. Viral antigen topographical distribution, presence of influenza A virus receptors in the brain, as well as, the role of the olfactory route in virus CNS invasion were studied using different immunohistochemistry techniques. Besides, viral RNA load in CSF and blood was quantified by means of a quantitative real-time reverse transcription-polymerase chain reaction. Viral antigen was observed widely distributed in the CNS, showing bilateral and symmetrical distribution in the nuclei of the diencephalon, mesencephalon and rhombencephalon. Viral RNA was detected in blood and CSF at one dpi, indicating that the virus crosses the blood-CSF-barrier early during infection. This early dissemination is possibly favoured by the presence of Siaα2,3 Gal and Siaα2,6 Gal receptors in brain vascular endothelial cells, and Siaα2,3 Gal receptors in ependymal and choroid plexus cells. No viral antigen was observed in olfactory sensory neurons, while the olfactory bulb showed only weak staining, suggesting that the virus did not use this pathway to enter into the brain. The sequence of virus appearance and the topographical distribution of this H7N1 HPAIV indicate that the viral entry occurs via the haematogenous route, with early and generalized spreading through the CSF.",2011 Oct 7,"['Chaves, Aida J', 'Busquets, Núria', 'Valle, Rosa', 'Rivas, Raquel', 'Vergara-Alert, Júlia', 'Dolz, Roser', 'Ramis, Antonio', 'Darji, Ayub', 'Majó, Natàlia']",Vet Res,,,True
34190b8df3ed825e3c49e41a3782d04acf1e21e9,PMC,Emergency department triage: an ethical analysis,http://dx.doi.org/10.1186/1471-227X-11-16,PMC3199257,21982119,CC BY,"BACKGROUND: Emergency departments across the globe follow a triage system in order to cope with overcrowding. The intention behind triage is to improve the emergency care and to prioritize cases in terms of clinical urgency. DISCUSSION: In emergency department triage, medical care might lead to adverse consequences like delay in providing care, compromise in privacy and confidentiality, poor physician-patient communication, failing to provide the necessary care altogether, or even having to decide whose life to save when not everyone can be saved. These consequences challenge the ethical quality of emergency care. This article provides an ethical analysis of ""routine"" emergency department triage. The four principles of biomedical ethics - viz. respect for autonomy, beneficence, nonmaleficence and justice provide the starting point and help us to identify the ethical challenges of emergency department triage. However, they do not offer a comprehensive ethical view. To address the ethical issues of emergency department triage from a more comprehensive ethical view, the care ethics perspective offers additional insights. SUMMARY: We integrate the results from the analysis using four principles of biomedical ethics into care ethics perspective on triage and propose an integrated clinically and ethically based framework of emergency department triage planning, as seen from a comprehensive ethics perspective that incorporates both the principles-based and care-oriented approach.",2011 Oct 7,"['Aacharya, Ramesh P', 'Gastmans, Chris', 'Denier, Yvonne']",BMC Emerg Med,,,True
9ea81809febb5da9242f91f23bc9e2fa4bfdeed6,PMC,Considerations on BVD eradication for the Irish livestock industry,http://dx.doi.org/10.1186/2046-0481-64-12,PMC3199273,21967764,CC BY,"Animal Health Ireland has produced clear guidelines for the control of Bovine Viral Diarrhoea (BVD) infection in Irish cattle herds. In the course of developing these guidelines it was clear that a framework for regional and/or national BVD control would be required to increase the uptake of BVD control at farm level and reduce the overall prevalence of the disease. This paper assessed the economic impact of BVD, epidemiological aspects of the disease to its control, models of BVD control, international experiences of BVD control programmes. The technical knowledge and test technology exists to eradicate BVD. Indeed, many countries have successfully and others are embarking on control of the disease. The identification and prompt elimination of PI cattle will form the basis of any control programme. The trade of such animals must be curtailed. Pregnant and potentially pregnant carrying PI foetuses pose a significant threat. International experience indicates systematic, well coordinated programmes have the most success, while voluntary programmes can make good initial progress but ultimately fail. The farming community must buy into any proposed programme, and without their support, failure is likely. To buy into the programme and create such a demand for BVD control, farmers must first be well informed. It is likely that stemming economic loss and improving productivity will be the primary motivator at individual farm level.",2011 Oct 3,"['Barrett, Damien J', 'More, Simon J', 'Graham, David A', ""O'Flaherty, Joe"", 'Doherty, Michael L', 'Gunn, H Michael']",Ir Vet J,,,True
f62a6a8b129d2104c5db1535b07e090ddf5ca7d3,PMC,Development of an optimized method for the detection of airborne viruses with real-time PCR analysis,http://dx.doi.org/10.1186/1743-422X-8-369,PMC3199808,21794150,CC BY,"BACKGROUND: Airborne viruses remain one of the major public health issues worldwide. Detection and quantification of airborne viruses is essential in order to provide information regarding public health risk assessment. FINDINGS: In this study, an optimized new, simple, low cost method for sampling of airborne viruses using Low Melting Agarose (LMA) plates and a conventional microbial air sampling device has been developed. The use of LMA plates permits the direct nucleic acids extraction of the captured viruses without the need of any preliminary elution step. Molecular detection and quantification of airborne viruses is performed using real-time quantitative (RT-)PCR (Q(RT-)PCR) technique. The method has been tested using Adenoviruses (AdVs) and Noroviruses (NoVs) GII, as representative DNA and RNA viruses, respectively. Moreover, the method has been tested successfully in outdoor experiments, by detecting and quantifying human adenoviruses (HAdVs) in the airborne environment of a wastewater treatment plant. CONCLUSIONS: The great advantage of LMA is that nucleic acids extraction is performed directly on the LMA plates, while the eluted nucleic acids are totally free of inhibitory substances. Coupled with QPCR the whole procedure can be completed in less than three (3) hours.",2011 Jul 27,"['Ziros, Panos G', 'Kokkinos, Petros A', 'Legaki, Euaggelia', 'Vantarakis, Apostolos']",Virol J,,,True
478eaa49054cba8f6ec4f2df3c6bfddd171e6ac5,PMC,Quercetin 7-rhamnoside reduces porcine epidemic diarrhea virus replication via independent pathway of viral induced reactive oxygen species,http://dx.doi.org/10.1186/1743-422X-8-460,PMC3200163,21967756,CC BY,"BACKGROUND: On the base of our previous study we were observed relevant studies on the hypothesis that the antiviral activity of quercetin 7-rhamnoside (Q7R), a flavonoid, won't relate ability of its antioxidant. METHODS: We were investigated the effects of Q7R on the cytopathic effects (CPE) by CPE reduction assay. Production of DNA fragment and reactive oxygen species (ROS) induced by PEDV infection were studied using DNA fragmentation assay and flow cytometry. RESULTS: In the course of this study it was discovered that Q7R is an extremely potent compound against PEDV. The addition of Q7R to PEDV-infected Vero cells directly reduced the formation of a visible cytopathic effect (CPE). Also, Q7R did not induce DNA fragmentation. Furthermore, ROS increased the infection of PEDV, which was strongly decreased by N-acetyl-L-cysteins (NAC). However, the increased ROS was not decreased by Q7R. Antiviral activity of antioxidants such as NAC, pyrrolidine dithiocarbamate (PDTC), and the vitamin E derivative, trolox, were hardly noticed. CONCLUSIONS: We concluded that the inhibition of PEDV production by Q7R is not simply due to a general action as an antioxidants and is highly specific, as several other antioxidants (NAC, PDTC, trolox) are inactive against PEDV infection.",2011 Oct 4,"['Song, Jae Hyoung', 'Shim, Jae Kwon', 'Choi, Hwa Jung']",Virol J,,,True
c1df508d29e27cafd7a54a39bc2e087caa3a6bc6,PMC,Use of Recombinant Adenovirus Vectored Consensus IFN-α to Avert Severe Arenavirus Infection,http://dx.doi.org/10.1371/journal.pone.0026072,PMC3200317,22039436,CC BY,"Several arenaviruses can cause viral hemorrhagic fever, a severe disease with case-fatality rates in hospitalized individuals ranging from 15-30%. Because of limited prophylaxis and treatment options, new medical countermeasures are needed for these viruses classified by the National Institutes of Allergy and Infectious Diseases (NIAID) as top priority biodefense Category A pathogens. Recombinant consensus interferon alpha (cIFN-α) is a licensed protein with broad clinical appeal. However, while cIFN-α has great therapeutic value, its utility for biodefense applications is hindered by its short in vivo half-life, mode and frequency of administration, and costly production. To address these limitations, we describe the use of DEF201, a replication-deficient adenovirus vector that drives the expression of cIFN-α, for pre- and post-exposure prophylaxis of acute arenaviral infection modeled in hamsters. Intranasal administration of DEF201 24 h prior to challenge with Pichindé virus (PICV) was highly effective at protecting animals from mortality and preventing viral replication and liver-associated disease. A significant protective effect was still observed with a single dosing of DEF201 given two weeks prior to PICV challenge. DEF201 was also efficacious when administered as a treatment 24 to 48 h post-virus exposure. The protective effect of DEF201 was largely attributed to the expression of cIFN-α, as dosing with a control empty vector adenovirus did not protect hamsters from lethal PICV challenge. Effective countermeasures that are highly stable, easily administered, and elicit long lasting protective immunity are much needed for arena and other viral infections. The DEF201 technology has the potential to address all of these issues and may serve as a broad-spectrum antiviral to enhance host defense against a number of viral pathogens.",2011 Oct 24,"['Gowen, Brian B.', 'Ennis, Jane', 'Russell, Andrew', 'Sefing, Eric J.', 'Wong, Min-Hui', 'Turner, Jeffrey']",PLoS One,,,True
9f8273bc745daf5c556f52ab081af19bb679db36,PMC,Coordinated Destruction of Cellular Messages in Translation Complexes by the Gammaherpesvirus Host Shutoff Factor and the Mammalian Exonuclease Xrn1,http://dx.doi.org/10.1371/journal.ppat.1002339,PMC3203186,22046136,CC BY,"Several viruses encode factors that promote host mRNA degradation to silence gene expression. It is unclear, however, whether cellular mRNA turnover pathways are engaged to assist in this process. In Kaposi's sarcoma-associated herpesvirus this phenotype is enacted by the host shutoff factor SOX. Here we show that SOX-induced mRNA turnover is a two-step process, in which mRNAs are first cleaved internally by SOX itself then degraded by the cellular exonuclease Xrn1. SOX therefore bypasses the regulatory steps of deadenylation and decapping normally required for Xrn1 activation. SOX is likely recruited to translating mRNAs, as it cosediments with translation initiation complexes and depletes polysomes. Cleaved mRNA intermediates accumulate in the 40S fraction, indicating that recognition occurs at an early stage of translation. This is the first example of a viral protein commandeering cellular mRNA turnover pathways to destroy host mRNAs, and suggests that Xrn1 is poised to deplete messages undergoing translation in mammalian cells.",2011 Oct 27,"['Covarrubias, Sergio', 'Gaglia, Marta M.', 'Kumar, G. Renuka', 'Wong, Wesley', 'Jackson, Andrew O.', 'Glaunsinger, Britt A.']",PLoS Pathog,,,True
3e418546d0b83c4b152b9e1200401bba25364427,PMC,IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry,http://dx.doi.org/10.1371/journal.ppat.1002337,PMC3203188,22046135,CC BY,"To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats.",2011 Oct 27,"['Feeley, Eric M.', 'Sims, Jennifer S.', 'John, Sinu P.', 'Chin, Christopher R.', 'Pertel, Thomas', 'Chen, Li-Mei', 'Gaiha, Gaurav D.', 'Ryan, Bethany J.', 'Donis, Ruben O.', 'Elledge, Stephen J.', 'Brass, Abraham L.']",PLoS Pathog,,,True
5eae2d5e8c253d92e131a68878bd286a0125d285,PMC,IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry,http://dx.doi.org/10.1371/journal.ppat.1002337,PMC3203188,22046135,CC BY,"To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats.",2011 Oct 27,"['Feeley, Eric M.', 'Sims, Jennifer S.', 'John, Sinu P.', 'Chin, Christopher R.', 'Pertel, Thomas', 'Chen, Li-Mei', 'Gaiha, Gaurav D.', 'Ryan, Bethany J.', 'Donis, Ruben O.', 'Elledge, Stephen J.', 'Brass, Abraham L.']",PLoS Pathog,,,False
578c5f9d94b117b9e424069af8a666db196975ec,PMC,IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry,http://dx.doi.org/10.1371/journal.ppat.1002337,PMC3203188,22046135,CC BY,"To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats.",2011 Oct 27,"['Feeley, Eric M.', 'Sims, Jennifer S.', 'John, Sinu P.', 'Chin, Christopher R.', 'Pertel, Thomas', 'Chen, Li-Mei', 'Gaiha, Gaurav D.', 'Ryan, Bethany J.', 'Donis, Ruben O.', 'Elledge, Stephen J.', 'Brass, Abraham L.']",PLoS Pathog,,,False
afef853959cbfdce6b6fe2d6e265e366002b9e84,PMC,IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry,http://dx.doi.org/10.1371/journal.ppat.1002337,PMC3203188,22046135,CC BY,"To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats.",2011 Oct 27,"['Feeley, Eric M.', 'Sims, Jennifer S.', 'John, Sinu P.', 'Chin, Christopher R.', 'Pertel, Thomas', 'Chen, Li-Mei', 'Gaiha, Gaurav D.', 'Ryan, Bethany J.', 'Donis, Ruben O.', 'Elledge, Stephen J.', 'Brass, Abraham L.']",PLoS Pathog,,,False
2e1c59f07b23de3ef6dee1ab75eb6e0334fd8349,PMC,IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry,http://dx.doi.org/10.1371/journal.ppat.1002337,PMC3203188,22046135,CC BY,"To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats.",2011 Oct 27,"['Feeley, Eric M.', 'Sims, Jennifer S.', 'John, Sinu P.', 'Chin, Christopher R.', 'Pertel, Thomas', 'Chen, Li-Mei', 'Gaiha, Gaurav D.', 'Ryan, Bethany J.', 'Donis, Ruben O.', 'Elledge, Stephen J.', 'Brass, Abraham L.']",PLoS Pathog,,,False
9fb6993f5fa1b94bdb2c132cf73d9dba2f848dcd,PMC,IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry,http://dx.doi.org/10.1371/journal.ppat.1002337,PMC3203188,22046135,CC BY,"To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats.",2011 Oct 27,"['Feeley, Eric M.', 'Sims, Jennifer S.', 'John, Sinu P.', 'Chin, Christopher R.', 'Pertel, Thomas', 'Chen, Li-Mei', 'Gaiha, Gaurav D.', 'Ryan, Bethany J.', 'Donis, Ruben O.', 'Elledge, Stephen J.', 'Brass, Abraham L.']",PLoS Pathog,,,False
190d780e909ab7bda97ffd708ec2cf05c7b3947c,PMC,IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry,http://dx.doi.org/10.1371/journal.ppat.1002337,PMC3203188,22046135,CC BY,"To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats.",2011 Oct 27,"['Feeley, Eric M.', 'Sims, Jennifer S.', 'John, Sinu P.', 'Chin, Christopher R.', 'Pertel, Thomas', 'Chen, Li-Mei', 'Gaiha, Gaurav D.', 'Ryan, Bethany J.', 'Donis, Ruben O.', 'Elledge, Stephen J.', 'Brass, Abraham L.']",PLoS Pathog,,,False
be627fe6c9548119d3357c35c9964ad795203329,PMC,IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry,http://dx.doi.org/10.1371/journal.ppat.1002337,PMC3203188,22046135,CC BY,"To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats.",2011 Oct 27,"['Feeley, Eric M.', 'Sims, Jennifer S.', 'John, Sinu P.', 'Chin, Christopher R.', 'Pertel, Thomas', 'Chen, Li-Mei', 'Gaiha, Gaurav D.', 'Ryan, Bethany J.', 'Donis, Ruben O.', 'Elledge, Stephen J.', 'Brass, Abraham L.']",PLoS Pathog,,,False
0b6e80d7ef4f79282798cb97d7d4e89afbb16153,PMC,IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry,http://dx.doi.org/10.1371/journal.ppat.1002337,PMC3203188,22046135,CC BY,"To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats.",2011 Oct 27,"['Feeley, Eric M.', 'Sims, Jennifer S.', 'John, Sinu P.', 'Chin, Christopher R.', 'Pertel, Thomas', 'Chen, Li-Mei', 'Gaiha, Gaurav D.', 'Ryan, Bethany J.', 'Donis, Ruben O.', 'Elledge, Stephen J.', 'Brass, Abraham L.']",PLoS Pathog,,,False
b4ad07bce8118121fa7a594ef203493eb4b68e2f,PMC,IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry,http://dx.doi.org/10.1371/journal.ppat.1002337,PMC3203188,22046135,CC BY,"To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats.",2011 Oct 27,"['Feeley, Eric M.', 'Sims, Jennifer S.', 'John, Sinu P.', 'Chin, Christopher R.', 'Pertel, Thomas', 'Chen, Li-Mei', 'Gaiha, Gaurav D.', 'Ryan, Bethany J.', 'Donis, Ruben O.', 'Elledge, Stephen J.', 'Brass, Abraham L.']",PLoS Pathog,,,False
70c40b30535abfc6d33eca8d9afcd2548452867c,PMC,IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry,http://dx.doi.org/10.1371/journal.ppat.1002337,PMC3203188,22046135,CC BY,"To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats.",2011 Oct 27,"['Feeley, Eric M.', 'Sims, Jennifer S.', 'John, Sinu P.', 'Chin, Christopher R.', 'Pertel, Thomas', 'Chen, Li-Mei', 'Gaiha, Gaurav D.', 'Ryan, Bethany J.', 'Donis, Ruben O.', 'Elledge, Stephen J.', 'Brass, Abraham L.']",PLoS Pathog,,,False
e92488019ca299d19beabb885c7c71b12b535712,PMC,The SARS-Coronavirus-Host Interactome: Identification of Cyclophilins as Target for Pan-Coronavirus Inhibitors,http://dx.doi.org/10.1371/journal.ppat.1002331,PMC3203193,22046132,CC BY,"Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) as interaction partners of the CoV non-structural protein 1 (Nsp1). These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA) blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock.",2011 Oct 27,"['Pfefferle, Susanne', 'Schöpf, Julia', 'Kögl, Manfred', 'Friedel, Caroline C.', 'Müller, Marcel A.', 'Carbajo-Lozoya, Javier', 'Stellberger, Thorsten', 'von Dall’Armi, Ekatarina', 'Herzog, Petra', 'Kallies, Stefan', 'Niemeyer, Daniela', 'Ditt, Vanessa', 'Kuri, Thomas', 'Züst, Roland', 'Pumpor, Ksenia', 'Hilgenfeld, Rolf', 'Schwarz, Frank', 'Zimmer, Ralf', 'Steffen, Imke', 'Weber, Friedemann', 'Thiel, Volker', 'Herrler, Georg', 'Thiel, Heinz-Jürgen', 'Schwegmann-Weßels, Christel', 'Pöhlmann, Stefan', 'Haas, Jürgen', 'Drosten, Christian', 'von Brunn, Albrecht']",PLoS Pathog,,,True
80ab1037161868297a622ae5e5e24a7f91d10bf5,PMC,Explaining rapid reinfections in multiple-wave influenza outbreaks: Tristan da Cunha 1971 epidemic as a case study,http://dx.doi.org/10.1098/rspb.2011.0300,PMC3203494,21525058,CC BY,"Influenza usually spreads through the human population in multiple-wave outbreaks. Successive reinfection of individuals over a short time interval has been explicitly reported during past pandemics. However, the causes of rapid reinfection and the role of reinfection in driving multiple-wave outbreaks remain poorly understood. To investigate these issues, we focus on a two-wave influenza A/H3N2 epidemic that occurred on the remote island of Tristan da Cunha in 1971. Over 59 days, 273 (96%) of 284 islanders experienced at least one attack and 92 (32%) experienced two attacks. We formulate six mathematical models invoking a variety of antigenic and immunological reinfection mechanisms. Using a maximum-likelihood analysis to confront model predictions with the reported incidence time series, we demonstrate that only two mechanisms can be retained: some hosts with either a delayed or deficient humoral immune response to the primary influenza infection were reinfected by the same strain, thus initiating the second epidemic wave. Both mechanisms are supported by previous empirical studies and may arise from a combination of genetic and ecological causes. We advocate that a better understanding and account of heterogeneity in the human immune response are essential to analysis of multiple-wave influenza outbreaks and pandemic planning.",2011 Dec 22,"['Camacho, Anton', 'Ballesteros, Sébastien', 'Graham, Andrea L.', 'Carrat, Fabrice', 'Ratmann, Oliver', 'Cazelles, Bernard']",Proc Biol Sci,,,True
a05173bdf26286064e4e13b8f5253330d9a9089b,PMC,Prior Virus Exposure Alters the Long-Term Landscape of Viral Replication during Feline Lentiviral Infection,http://dx.doi.org/10.3390/v3101891,PMC3205387,22069521,CC BY,"We developed a feline model of lentiviral cross-species transmission using a puma lentivirus (PLV or FIV(Pco)) which infects domestic cats but does not cause disease. Infection with PLV protects cats from CD4+ T-cell decline caused by subsequent infection with virulent feline immunodeficiency virus (FIV). Previous studies implicate innate immune and/or cellular restriction mechanisms for FIV disease attenuation in PLV-infected cats. In this study, we evaluated viral infection and cytokine mRNA transcription in 12 different tissue reservoirs approximately five months post infection. We quantitated tissue proviral load, viral mRNA load and relative transcription of IL-10, IL-12p40 and IFNγ from tissues of cats exposed to FIV, PLV or both viruses and analyzed these parameters using a multivariate statistical approach. The distribution and intensity of FIV infection and IFNγ transcription differed between single and co-infected cats, characterized by higher FIV proviral loads and IFNγ expression in co-infected cat tissues. Variability in FIV mRNA load and IFNγ was significantly more constrained in co-infected versus singly infected cat tissues. Single-infected:co-infected ratios of FIV mRNA load compared to FIV proviral load indicated that active viral transcription was apparently inhibited during co-infection. These results indicate that previous PLV infection increases activation of tissue innate immunity and constrains the ability of FIV to productively infect tissue reservoirs of infection for months, independent of FIV proviral load, supporting a model in which innate immunity and/or modulation of target cell susceptibility play a key role in PLV-induced protection from FIV disease.",2011 Oct 13,"['Zheng, Xin', 'Carver, Scott', 'Troyer, Ryan M.', 'Terwee, Julie A.', 'VandeWoude, Sue']",Viruses,,,True
93bc12e23681301901cc72598ded5258b4455eb1,PMC,The Molecular Biology of Frog Virus 3 and other Iridoviruses Infecting Cold-Blooded Vertebrates,http://dx.doi.org/10.3390/v3101959,PMC3205390,22069524,CC BY,"Frog virus 3 (FV3) is the best characterized member of the family Iridoviridae. FV3 study has provided insights into the replication of other family members, and has served as a model of viral transcription, genome replication, and virus-mediated host-shutoff. Although the broad outlines of FV3 replication have been elucidated, the precise roles of most viral proteins remain unknown. Current studies using knock down (KD) mediated by antisense morpholino oligonucleotides (asMO) and small, interfering RNAs (siRNA), knock out (KO) following replacement of the targeted gene with a selectable marker by homologous recombination, ectopic viral gene expression, and recombinant viral proteins have enabled researchers to systematically ascertain replicative- and virulence-related gene functions. In addition, the application of molecular tools to ecological studies is providing novel ways for field biologists to identify potential pathogens, quantify infections, and trace the evolution of ecologically important viral species. In this review, we summarize current studies using not only FV3, but also other iridoviruses infecting ectotherms. As described below, general principles ascertained using FV3 served as a model for the family, and studies utilizing other ranaviruses and megalocytiviruses have confirmed and extended our understanding of iridovirus replication. Collectively, these and future efforts will elucidate molecular events in viral replication, intrinsic and extrinsic factors that contribute to disease outbreaks, and the role of the host immune system in protection from disease.",2011 Oct 20,"['Chinchar, V. Gregory', 'Yu, Kwang H.', 'Jancovich, James K.']",Viruses,,,True
8235178d45091e3c395321a0af42c92ef0c504ef,PMC,A Basic Strategy to Manage Global Health with Reference to Livestock Production in Asia,http://dx.doi.org/10.4061/2011/328307,PMC3206505,22135772,CC BY,"Newly emerging infectious diseases (nEIDs) have increased rapidly presenting alarming challenges to global health. We argue that for effective management of global health a basic strategy should include at least three essential tactical forms: actions of a directly focused nature, institutional coordination, and disciplinary integration in approaches to health management. Each level of action is illustrated with examples from the livestock sector in Asia. No clear example of all three tactical forms in place can be found from developing countries where food security is a significant threat although Vietnam is developing a comprehensive strategy. Finally, an ecosystem health approach to global health management is advocated; such an approach moves away from the traditional single disciplinary approach. Stronger guidance is needed to direct ecohealth research and application in the management of global health.",2011 Oct 31,"['Hall, David C.', 'Le, Quynh Ba']",Vet Med Int,,,True
8a5e57ed05714b7baedeaece51bec78b4b8d1447,PMC,NNAlign: A Web-Based Prediction Method Allowing Non-Expert End-User Discovery of Sequence Motifs in Quantitative Peptide Data,http://dx.doi.org/10.1371/journal.pone.0026781,PMC3206854,22073191,CC BY,"Recent advances in high-throughput technologies have made it possible to generate both gene and protein sequence data at an unprecedented rate and scale thereby enabling entirely new “omics”-based approaches towards the analysis of complex biological processes. However, the amount and complexity of data that even a single experiment can produce seriously challenges researchers with limited bioinformatics expertise, who need to handle, analyze and interpret the data before it can be understood in a biological context. Thus, there is an unmet need for tools allowing non-bioinformatics users to interpret large data sets. We have recently developed a method, NNAlign, which is generally applicable to any biological problem where quantitative peptide data is available. This method efficiently identifies underlying sequence patterns by simultaneously aligning peptide sequences and identifying motifs associated with quantitative readouts. Here, we provide a web-based implementation of NNAlign allowing non-expert end-users to submit their data (optionally adjusting method parameters), and in return receive a trained method (including a visual representation of the identified motif) that subsequently can be used as prediction method and applied to unknown proteins/peptides. We have successfully applied this method to several different data sets including peptide microarray-derived sets containing more than 100,000 data points. NNAlign is available online at http://www.cbs.dtu.dk/services/NNAlign.",2011 Nov 2,"['Andreatta, Massimo', 'Schafer-Nielsen, Claus', 'Lund, Ole', 'Buus, Søren', 'Nielsen, Morten']",PLoS One,,,True
cc33658b1e2bfebb81adf4b6befe9cb37f6f6f16,PMC,"Profiling of Substrate Specificities of 3C-Like Proteases from Group 1, 2a, 2b, and 3 Coronaviruses",http://dx.doi.org/10.1371/journal.pone.0027228,PMC3206940,22073294,CC0,"BACKGROUND: Coronaviruses (CoVs) can be classified into alphacoronavirus (group 1), betacoronavirus (group 2), and gammacoronavirus (group 3) based on diversity of the protein sequences. Their 3C-like protease (3CL(pro)), which catalyzes the proteolytic processing of the polyproteins for viral replication, is a potential target for anti-coronaviral infection. METHODOLOGY/PRINCIPAL FINDINGS: Here, we profiled the substrate specificities of 3CL(pro) from human CoV NL63 (group 1), human CoV OC43 (group 2a), severe acute respiratory syndrome coronavirus (SARS-CoV) (group 2b) and infectious bronchitis virus (IBV) (group 3), by measuring their activity against a substrate library of 19×8 of variants with single substitutions at P5 to P3' positions. The results were correlated with structural properties like side chain volume, hydrophobicity, and secondary structure propensities of substituting residues. All 3CL(pro) prefer Gln at P1 position, Leu at P2 position, basic residues at P3 position, small hydrophobic residues at P4 position, and small residues at P1' and P2' positions. Despite 3CL(pro) from different groups of CoVs share many similarities in substrate specificities, differences in substrate specificities were observed at P4 positions, with IBV 3CL(pro) prefers P4-Pro and SARS-CoV 3CL(pro) prefers P4-Val. By combining the most favorable residues at P3 to P5 positions, we identified super-active substrate sequences ‘VARLQ↓SGF’ that can be cleaved efficiently by all 3CL(pro) with relative activity of 1.7 to 3.2, and ‘VPRLQ↓SGF’ that can be cleaved specifically by IBV 3CL(pro) with relative activity of 4.3. CONCLUSIONS/SIGNIFICANCE: The comprehensive substrate specificities of 3CL(pro) from each of the group 1, 2a, 2b, and 3 CoVs have been profiled in this study, which may provide insights into a rational design of broad-spectrum peptidomimetic inhibitors targeting the proteases.",2011 Nov 2,"['Chuck, Chi-Pang', 'Chow, Hak-Fun', 'Wan, David Chi-Cheong', 'Wong, Kam-Bo']",PLoS One,,,True
c6518c58374cc315647f2873a234cfa983746bfd,PMC,Insights into N-calls of mitochondrial DNA sequencing using MitoChip v2.0,http://dx.doi.org/10.1186/1756-0500-4-426,PMC3208482,22011414,CC BY,"BACKGROUND: Developments in DNA resequencing microarrays include mitochondrial DNA (mtDNA) sequencing and mutation detection. Failure by the microarray to identify a base, compared to the reference sequence, is designated an 'N-call.' This study re-examined the N-call distribution of mtDNA samples sequenced by the Affymetrix MitoChip v.2.0, based on the hypothesis that N-calls may represent insertions or deletions (indels) in mtDNA. FINDINGS: We analysed 16 patient mtDNA samples using MitoChip. N-calls by the proprietary GSEQ software were significantly reduced when either of the freeware on-line algorithms ResqMi or sPROFILER was utilized. With sPROFILER, this decrease in N-calls had no effect on the homoplasmic or heteroplasmic mutation levels compared to GSEQ software, but ResqMi produced a significant change in mutation load, as well as producing longer N-cell stretches. For these reasons, further analysis using ResqMi was not attempted. Conventional DNA sequencing of the longer N-calls stretches from sPROFILER revealed 7 insertions and 12 point mutations. Moreover, analysis of single-base N-calls of one mtDNA sample found 3 other point mutations. CONCLUSIONS: Our study is the first to analyse N-calls produced from GSEQ software for the MitoChipv2.0. By narrowing the focus to longer stretches of N-calls revealed by sPROFILER, conventional sequencing was able to identify unique insertions and point mutations. Shorter N-calls also harboured point mutations, but the absence of deletions among N-calls suggests that probe confirmation affects binding and thus N-calling. This study supports the contention that the GSEQ is more capable of assigning bases when used in conjunction with sPROFILER.",2011 Oct 20,"['Zamzami, Mazin A', 'Price, Gareth R', 'Taylor, Robert W', 'Blakely, Emma L', 'Oancea, Iulia', 'Bowling, Francis', 'Duley, John A']",BMC Res Notes,,,True
2a1e091e9ed956fa71921a76e014e1694c855d04,PMC,Knowledge and awareness of tuberculosis among Roma population in Belgrade: a qualitative study,http://dx.doi.org/10.1186/1471-2334-11-284,PMC3210101,22023788,CC BY,"BACKGROUND: Tuberculosis (TB) remains an important health problem in the Roma population in Serbia. Recent studies have highlighted the importance of increasing awareness of TB and reducing the associated stigmas to reduce the incidence of TB and enable earlier diagnosis and effective treatment. This study investigated the knowledge and beliefs about transmission, symptoms and treatment of TB as well as attitudes towards patients with TB among the Roma population in Belgrade. METHODS: The focus-group method was considered to be appropriate for investigating knowledge and beliefs about TB. A total of 24 Roma people aged 19-55 years participated in three focus-group discussions. RESULTS: All participants knew that TB was a pulmonary disease and could be contagious. Saliva was the most commonly mentioned mode of transmission. Some individuals thought, albeit hesitantly, that TB could be transmitted by shaking hands with an infected individual. Of factors contributing to TB, participants mentioned bad living conditions, low quality and lack of food, and stress. Participants quoted chest pain, cough, haemoptysis, loss of appetite, loss of weight, weakness and sweating as basic symptoms of TB. Participants believed that effective treatment should include resting, taking prescribed medicines, inhaling fresh air and eating ""strong"" food such as bacon and pork; these approaches were considered as important as taking antibiotics). In addition, participants mentioned that they use some folk medicines. Relatives and friends, and to a lesser extent television, were the main sources of information about TB. Participants most appreciate personal contact with doctors as a source of information. CONCLUSIONS: We concluded that participants were aware of the seriousness TB as well as some of the modes of transmission; however, they had some misconceptions. An important finding was the confidence in doctors expressed by the Roma people.",2011 Oct 24,"['Vukovic, Dejana S', 'Nagorni-Obradovic, Ljudmila M']",BMC Infect Dis,,,True
8e3230d271fea2714dd544af802180200812419d,PMC,New Tetromycin Derivatives with Anti-Trypanosomal and Protease Inhibitory Activities,http://dx.doi.org/10.3390/md9101682,PMC3210601,22072992,CC BY,"Four new tetromycin derivatives, tetromycins 1–4 and a previously known one, tetromycin B (5) were isolated from Streptomyces axinellae Pol001(T) cultivated from the Mediterranean sponge Axinella polypoides. Structures were assigned using extensive 1D and 2D NMR spectroscopy as well as HRESIMS analysis. The compounds were tested for antiparasitic activities against Leishmania major and Trypanosoma brucei, and for protease inhibition against several cysteine proteases such as falcipain, rhodesain, cathepsin L, cathepsin B, and viral proteases SARS-CoV M(pro), and PL(pro). The compounds showed antiparasitic activities against T. brucei and time-dependent inhibition of cathepsin L-like proteases with K(i) values in the low micromolar range.",2011 Sep 26,"['Pimentel-Elardo, Sheila M.', 'Buback, Verena', 'Gulder, Tobias A.M.', 'Bugni, Tim S.', 'Reppart, Jason', 'Bringmann, Gerhard', 'Ireland, Chris M.', 'Schirmeister, Tanja', 'Hentschel, Ute']",Mar Drugs,,,True
e30f5f76a403e0a60d32f941c32fb5e0cd08c458,PMC,"Involvement of FOXO Transcription Factors, TRAIL-FasL/Fas, and Sirtuin Proteins Family in Canine Coronavirus Type II-Induced Apoptosis",http://dx.doi.org/10.1371/journal.pone.0027313,PMC3210785,22087287,CC BY,"n our previous study, we have shown that canine coronavirus type II (CCoV-II) activates both extrinsic and intrinsic apoptotic pathway in a canine fibrosarcoma cell line (A-72 cells). Herein we investigated the role of Sirtuin and Forkhead box O (FOXO) families in this experimental model using Nortern Blot and Western Blot analysis. Our results demonstrated that mitochondrial SIRT3 and SIRT4 protein expression increased from 12 and 24 h post infection (p.i.) onwards, respectively, whereas the nuclear SIRT1 expression increased during the first 12 h p.i. followed by a decrease after 36 h p.i., reaching the same level of control at 48 h p.i. Sirtuins interact with/and regulate the activity of FOXO family proteins, and we herein observed that FOXO3A and FOXO1 expression increased significantly and stably from 12 h p.i. onwards. In addition, CCoV-II induces a remarkable increase in the expression of TNF-related apoptosis-inducing ligand (TRAIL), while we observed a slight up-regulation of FasL/Fas at 36 p.i. with a decrease of both proteins at the end of infection. Furthermore, we found that virus infection increased both bax translocation into mitochondria and decreased bcl-2 expression in cytosol in a time-dependent manner. These data suggest that FOXO transcription factors mediate pro-apoptotic effects of CCoV-II, in part due to activation of extrinsic apoptosis pathway, while some Sirtuin family members (such as SIRT3 and SIRT4) may be involved in intrinsic apoptotic pathway. Moreover, these results propose that TRAIL is an important mediator of cell death induced by CCoV-II during in vitro infection.",2011 Nov 8,"['Marfè, Gabriella', 'Tafani, Marco', 'Fiorito, Filomena', 'Pagnini, Ugo', 'Iovane, Giuseppe', 'De Martino, Luisa']",PLoS One,,,True
f5fe14c66ff48ce3cff7c81201c1800cb725b097,PMC,Endogenous annexin A1 counter-regulates bleomycin-induced lung fibrosis,http://dx.doi.org/10.1186/1471-2172-12-59,PMC3212807,22011168,CC BY,"BACKGROUND: The balancing functions of pro/anti-inflammatory mediators of the complex innate responses have been investigated in a variety of experimental inflammatory settings. Annexin-A1 (AnxA1) is one mediator of endogenous anti-inflammation, affording regulation of leukocyte trafficking and activation in many contexts, yet its role in lung pathologies has been scarcely investigated, despite being highly expressed in lung cells. Here we have applied the bleomycin lung fibrosis model to AnxA1 null mice over a 21-day time-course, to monitor potential impact of this mediator on the control of the inflammatory and fibrotic phases. RESULTS: Analyses in wild-type mice revealed strict spatial and temporal regulation of the Anxa1 gene, e.g. up-regulation in epithelial cells and infiltrated granulocytes at day 7, followed by augmented protein levels in alveolar macrophages by day 21. Absence of AnxA1 caused increases in: i) the degree of inflammation at day 7; and ii) indexes of fibrosis (assessed by deposition of hydroxyproline in the lung) at day 7 and 21. These alterations in AnxA1 null mice were paralleled by augmented TGF-β1, IFN-γ and TNF-α generation compared to wild-type mice. Finally, treatment of wild type animals with an AnxA1 peptido-mimetic, given prophylactically (from day 0 to 21) or therapeutically (from day 14 onward), ameliorated both signs of inflammation and fibrosis. CONCLUSION: Collectively these data reveal a pathophysiological relevance for endogenous AnxA1 in lung inflammation and, more importantly, fibrosis, and may open new insights for the pharmacological treatment of lung fibrosis.",2011 Oct 19,"['Damazo, Amílcar S', 'Sampaio, André LF', 'Nakata, Cintia MAG', 'Flower, Roderick J', 'Perretti, Mauro', 'Oliani, Sonia M']",BMC Immunol,,,True
64e2d8f1f9eccda51fa3b8398c20e040c7fbcd06,PMC,Lycorine reduces mortality of human enterovirus 71-infected mice by inhibiting virus replication,http://dx.doi.org/10.1186/1743-422X-8-483,PMC3212826,22029605,CC BY,"Human enterovirus 71 (EV71) infection causes hand, foot and mouth disease in children under 6 years old and this infection occasionally induces severe neurological complications. No vaccines or drugs are clinical available to control EV71 epidemics. In present study, we show that treatment with lycorine reduced the viral cytopathic effect (CPE) on rhabdomyosarcoma (RD) cells by inhibiting virus replication. Analysis of this inhibitory effect of lycorine on viral proteins synthesis suggests that lycorine blocks the elongation of the viral polyprotein during translation. Lycorine treatment of mice challenged with a lethal dose of EV71 resulted in reduction of mortality, clinical scores and pathological changes in the muscles of mice, which were achieved through inhibition of viral replication. When mice were infected with a moderate dose of EV71, lycorine treatment was able to protect them from paralysis. Lycorine may be a potential drug candidate for the clinical treatment of EV71-infected patients.",2011 Oct 27,"['Liu, Jiangning', 'Yang, Yajun', 'Xu, Yanfeng', 'Ma, Chunmei', 'Qin, Chuan', 'Zhang, Lianfeng']",Virol J,,,True
d1d4ae8dd542e752e472532a2509525e22168568,PMC,Epidemiology and immunoprotection of nephropathogenic avian infectious bronchitis virus in southern China,http://dx.doi.org/10.1186/1743-422X-8-484,PMC3212842,22032619,CC BY,"BACKGROUND: In last three years, 96 suspected poultry farms from different provinces in China were diagnosed for avian infectious bronchitis (IB) survey. Finally, 221 IBV strains were confirmed by dwarf embryo test and RT-PCR assay. By virus recovery trials, 187 of the isolates caused the birds died or distressed from nephritis, which was accordant with the clinical record. RESULTS: Based on epidemiology analysis of recent field isolates of nephropathogenic IB in vaccinated farms in China, YL6 strain were used for vaccination and evaluated by antibody titer and challenge tests. The immunoprotection test indicated that the practical application of vaccine based on the recent field strains could finely facilitate controlling the nephropathogenic IB. CONCLUSIONS: Our study was aim at setting a guide for safeguard against nephropathogenic IBV-caused disease in China.",2011 Oct 27,"['Xie, Qingmei', 'Ji, Jun', 'Xie, Jingwei', 'Chen, Feng', 'Cai, Manshan', 'Sun, Baoli', 'Xue, Chunyi', 'Ma, Jingyun', 'Bi, Yingzuo']",Virol J,,,True
612fc352956cba3b9e5e74179125dc5d9aadba23,PMC,Mismatched single stranded antisense oligonucleotides can induce efficient dystrophin splice switching,http://dx.doi.org/10.1186/1471-2350-12-141,PMC3213239,22013876,CC BY,"BACKGROUND: Antisense oligomer induced exon skipping aims to reduce the severity of Duchenne muscular dystrophy by redirecting splicing during pre-RNA processing such that the causative mutation is by-passed and a shorter but partially functional Becker muscular dystrophy-like dystrophin isoform is produced. Normal exons are generally targeted to restore the dystrophin reading frame however, an appreciable subset of dystrophin mutations are intra-exonic and therefore have the potential to compromise oligomer efficiency, necessitating personalised oligomer design for some patients. Although antisense oligomers are easily personalised, it remains unclear whether all patient polymorphisms within antisense oligomer target sequences will require the costly process of producing and validating patient specific compounds. METHODS: Here we report preclinical testing of a panel of splice switching antisense oligomers, designed to excise exon 25 from the dystrophin transcript, in normal and dystrophic patient cells. These patient cells harbour a single base insertion in exon 25 that lies within the target sequence of an oligomer shown to be effective at removing exon 25. RESULTS: It was anticipated that such a mutation would compromise oligomer binding and efficiency. However, we show that, despite the mismatch an oligomer, designed and optimised to excise exon 25 from the normal dystrophin mRNA, removes the mutated exon 25 more efficiently than the mutation-specific oligomer. CONCLUSION: This raises the possibility that mismatched AOs could still be therapeutically applicable in some cases, negating the necessity to produce patient-specific compounds.",2011 Oct 20,"['Fragall, Clayton T', 'Adams, Abbie M', 'Johnsen, Russell D', 'Kole, Ryszard', 'Fletcher, Sue', 'Wilton, Steve D']",BMC Med Genet,,,True
6d6e142b8ccce1104fecb15ccc6b62433552a013,PMC,LAVA: An Open-Source Approach To Designing LAMP (Loop-Mediated Isothermal Amplification) DNA Signatures,http://dx.doi.org/10.1186/1471-2105-12-240,PMC3213686,21679460,CC BY,"BACKGROUND: We developed an extendable open-source Loop-mediated isothermal AMPlification (LAMP) signature design program called LAVA (LAMP Assay Versatile Analysis). LAVA was created in response to limitations of existing LAMP signature programs. RESULTS: LAVA identifies combinations of six primer regions for basic LAMP signatures, or combinations of eight primer regions for LAMP signatures with loop primers, which can be used as LAMP signatures. The identified primers are conserved among target organism sequences. Primer combinations are optimized based on lengths, melting temperatures, and spacing among primer sites. We compare LAMP signature candidates for Staphylococcus aureus created both by LAVA and by PrimerExplorer. We also include signatures from a sample run targeting all strains of Mycobacterium tuberculosis. CONCLUSIONS: We have designed and demonstrated new software for identifying signature candidates appropriate for LAMP assays. The software is available for download at http://lava-dna.googlecode.com/.",2011 Jun 16,"['Torres, Clinton', 'Vitalis, Elizabeth A', 'Baker, Brian R', 'Gardner, Shea N', 'Torres, Marisa W', 'Dzenitis, John M']",BMC Bioinformatics,,,True
23e37316e27cec6fe0e71647552b1f7b0e9255b2,PMC,Construction and Characterization of Single-Chain Variable Fragment Antibody Library Derived from Germline Rearranged Immunoglobulin Variable Genes,http://dx.doi.org/10.1371/journal.pone.0027406,PMC3214059,22096568,CC BY,"Antibody repertoires for library construction are conventionally harvested from mRNAs of immune cells. To examine whether germline rearranged immunoglobulin (Ig) variable region genes could be used as source of antibody repertoire, an immunized phage-displayed scFv library was prepared using splenocytic genomic DNA as template. In addition, a novel frame-shifting PCR (fsPCR) step was introduced to rescue stop codon and to enhance diversity of the complementarity-determining region 3 (CDR3). The germline scFv library was initially characterized against the hapten antigen phenyloxazolone (phOx). Sequence analysis of the phOx-selective scFvs indicated that the CDRs consisted of novel as well as conserved motifs. In order to illustrate that the diversity of CDR3 was increased by the fsPCR step, a second scFv library was constructed using a single scFv clone L3G7C as a template. Despite showing similar binding characteristics towards phOx, the scFv clones that were obtained from the L3G7C-derived antibody library gave a lower non-specific binding than that of the parental L3G7C clone. To determine whether germline library represented the endogenous immune status, specific scFv clones for nucleocapsid (N) protein of SARS-associated coronavirus (SCoV) were obtained both from naïve and immunized germline scFv libraries. Both libraries yielded specific anti-N scFvs that exhibited similar binding characteristics towards recombinant N protein, except the immunized library gave a larger number of specific anti-N scFv, and clones with identical nucleotide sequences were found. In conclusion, highly diversified antibody library can be efficiently constructed using germline rearranged immunoglobulin variable genes as source of antibody repertoires and fsPCR to diversify the CDR3.",2011 Nov 11,"['Cheng, Man', 'Chan, Shirley Y. W.', 'Zhao, Qi', 'Chan, Elaine Y. M.', 'Au, Shannon W. N.', 'Lee, Susanna S. T.', 'Cheung, Wing-Tai']",PLoS One,,,True
3d91cc711f18ce05f6d63c11760e3ff4fd88928a,PMC,Evaluation of Approaches to Identify the Targets of Cellular Immunity on a Proteome-Wide Scale,http://dx.doi.org/10.1371/journal.pone.0027666,PMC3214079,22096610,CC BY,"BACKGROUND: Vaccine development against malaria and other complex diseases remains a challenge for the scientific community. The recent elucidation of the genome, proteome and transcriptome of many of these complex pathogens provides the basis for rational vaccine design by identifying, on a proteome-wide scale, novel target antigens that are recognized by T cells and antibodies from exposed individuals. However, there is currently no algorithm to effectively identify important target antigens from genome sequence data; this is especially challenging for T cell targets. Furthermore, for some of these pathogens, such as Plasmodium, protein expression using conventional platforms has been problematic but cell-free in vitro transcription translation (IVTT) strategies have recently proved successful. Herein, we report a novel approach for proteome-wide scale identification of the antigenic targets of T cell responses using IVTT products. PRINCIPAL FINDINGS: We conducted a series of in vitro and in vivo experiments using IVTT proteins either unpurified, absorbed to carboxylated polybeads, or affinity purified through nickel resin or magnetic beads. In vitro studies in humans using CMV, EBV, and Influenza A virus proteins showed antigen-specific cytokine production in ELIspot and Cytometric Bead Array assays with cells stimulated with purified or unpurified IVTT antigens. In vitro and in vivo studies in mice immunized with the Plasmodium yoelii circumsporozoite DNA vaccine with or without IVTT protein boost showed antigen-specific cytokine production using purified IVTT antigens only. Overall, the nickel resin method of IVTT antigen purification proved optimal in both human and murine systems. CONCLUSIONS: This work provides proof of concept for the potential of high-throughput approaches to identify T cell targets of complex parasitic, viral or bacterial pathogens from genomic sequence data, for rational vaccine development against emerging and re-emerging diseases that pose a threat to public health.",2011 Nov 11,"['Cardoso, Fernanda C.', 'Roddick, Joanne S.', 'Groves, Penny', 'Doolan, Denise L.']",PLoS One,,,True
379dc32e1a173ffb789b66c9dccea4219ace8fde,PMC,Immunogenetic Factors Associated with Severe Respiratory Illness Caused by Zoonotic H1N1 and H5N1 Influenza Viruses,http://dx.doi.org/10.1155/2012/797180,PMC3216312,22110538,CC BY,"Following the 2009 H1N1 pandemic and ongoing sporadic avian-to-human transmission of H5N1 viruses, an emphasis has been placed on better understanding the determinants and pathogenesis of severe influenza infections. Much of the current literature has focused on viral genetics and its impact on host immunity as well as novel risk factors for severe infection (particularly within the H1N1 pandemic). An understanding of the host genetic determinants of susceptibility and severe respiratory illness, however, is currently lacking. By better defining the role of genetic variability in influenza infection and identifying key polymorphisms that impair the host immune response or correlate with protection, we will be able to better identify at-risk populations and new targets for therapeutic interventions and vaccines. This paper will summarize known immunogenetic factors associated with susceptibility or severity of both pH1N1 and H5N1 infections and will also identify genetic pathways and polymorphisms of high relevance for future study.",2012 Nov 3,"['Juno, Jennifer', 'Fowke, Keith R.', 'Keynan, Yoav']",Clin Dev Immunol,,,True
98d83658e5a7c2174de3524a9a3b7c057a34b085,PMC,Angiotensin-Converting Enzyme 2: The First Decade,http://dx.doi.org/10.1155/2012/307315,PMC3216391,22121476,CC BY,"The renin-angiotensin system (RAS) is a critical regulator of hypertension, primarily through the actions of the vasoactive peptide Ang II, which is generated by the action of angiotensin-converting enzyme (ACE) mediating an increase in blood pressure. The discovery of ACE2, which primarily metabolises Ang II into the vasodilatory Ang-(1-7), has added a new dimension to the traditional RAS. As a result there has been huge interest in ACE2 over the past decade as a potential therapeutic for lowering blood pressure, especially elevation resulting from excess Ang II. Studies focusing on ACE2 have helped to reveal other actions of Ang-(1-7), outside vasodilation, such as antifibrotic and antiproliferative effects. Moreover, investigations focusing on ACE2 have revealed a variety of roles not just catalytic but also as a viral receptor and amino acid transporter. This paper focuses on what is known about ACE2 and its biological roles, paying particular attention to the regulation of ACE2 expression. In light of the entrance of human recombinant ACE2 into clinical trials, we discuss the potential use of ACE2 as a therapeutic and highlight some pertinent questions that still remain unanswered about ACE2.",2012 Nov 10,"['Clarke, Nicola E.', 'Turner, Anthony J.']",Int J Hypertens,,,True
a760c40de63cc6df4ba38766deb3fbb54724ee44,PMC,"In China, Students in Crowded Dormitories with a Low Ventilation Rate Have More Common Colds: Evidence for Airborne Transmission",http://dx.doi.org/10.1371/journal.pone.0027140,PMC3217956,22110607,CC BY,"OBJECTIVE: To test whether the incidence of common colds among college students in China is associated with ventilation rates and crowdedness in dormitories. METHODS: In Phase I of the study, a cross-sectional study, 3712 students living in 1569 dorm rooms in 13 buildings responded to a questionnaire about incidence and duration of common colds in the previous 12 months. In Phase II, air temperature, relative humidity and CO(2) concentration were measured for 24 hours in 238 dorm rooms in 13 buildings, during both summer and winter. Out-to indoor air flow rates at night were calculated based on measured CO(2) concentrations. RESULTS: In Phase I, 10% of college students reported an incidence of more than 6 common colds in the previous 12 months, and 15% reported that each infection usually lasted for more than 2 weeks. Students in 6-person dorm rooms were about 2 times as likely to have an incidence of common colds ≥6 times per year and a duration ≥2 weeks, compared to students in 3-person rooms. In Phase II, 90% of the measured dorm rooms had an out-to indoor air flow rate less than the Chinese standard of 8.3 L/s per person during the heating season. There was a dose-response relationship between out-to indoor air flow rate per person in dorm rooms and the proportion of occupants with annual common cold infections ≥6 times. A mean ventilation rate of 5 L/(s•person) in dorm buildings was associated with 5% of self reported common cold ≥6 times, compared to 35% at 1 L/(s•person). CONCLUSION: Crowded dormitories with low out-to indoor airflow rates are associated with more respiratory infections among college students.",2011 Nov 16,"['Sun, Yuexia', 'Wang, Zhigang', 'Zhang, Yufeng', 'Sundell, Jan']",PLoS One,,,True
3e6e8f31ed44595ef47bb2d50934901e5d681654,PMC,An optimized microarray platform for assaying genomic variation in Plasmodium falciparum field populations,http://dx.doi.org/10.1186/gb-2011-12-4-r35,PMC3218861,21477297,CC BY,"We present an optimized probe design for copy number variation (CNV) and SNP genotyping in the Plasmodium falciparum genome. We demonstrate that variable length and isothermal probes are superior to static length probes. We show that sample preparation and hybridization conditions mitigate the effects of host DNA contamination in field samples. The microarray and workflow presented can be used to identify CNVs and SNPs with 95% accuracy in a single hybridization, in field samples containing up to 92% human DNA contamination.",2011 Apr 8,"['Tan, John C', 'Miller, Becky A', 'Tan, Asako', 'Patel, Jigar J', 'Cheeseman, Ian H', 'Anderson, Tim JC', 'Manske, Magnus', 'Maslen, Gareth', 'Kwiatkowski, Dominic P', 'Ferdig, Michael T']",Genome Biol,,,True
a3149d976fd2e03be5159c041a0241f00597e097,PMC,Host adaptive immunity deficiency in severe pandemic influenza,http://dx.doi.org/10.1186/cc9259,PMC3219262,20840779,CC BY,"INTRODUCTION: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. METHODS: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. RESULTS: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. CONCLUSIONS: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.",2010 Sep 14,"['Bermejo-Martin, Jesus F', 'Martin-Loeches, Ignacio', 'Rello, Jordi', 'Antón, Andres', 'Almansa, Raquel', 'Xu, Luoling', 'Lopez-Campos, Guillermo', 'Pumarola, Tomás', 'Ran, Longsi', 'Ramirez, Paula', 'Banner, David', 'Cheuk Ng, Derek', 'Socias, Lorenzo', 'Loza, Ana', 'Andaluz, David', 'Maravi, Enrique', 'Gómez-Sánchez, Maria J', 'Gordón, Mónica', 'Gallegos, Maria C', 'Fernandez, Victoria', 'Aldunate, Sara', 'León, Cristobal', 'Merino, Pedro', 'Blanco, Jesús', 'Martin-Sanchez, Fernando', 'Rico, Lucia', 'Varillas, David', 'Iglesias, Veronica', 'Marcos, Maria Ángeles', 'Gandía, Francisco', 'Bobillo, Felipe', 'Nogueira, Begoña', 'Rojo, Silvia', 'Resino, Salvador', 'Castro, Carmen', 'Ortiz de Lejarazu, Raul', 'Kelvin, David']",Crit Care,,,True
2562be331505d02d68f554fdb894ff2bb9ebe798,PMC,Host adaptive immunity deficiency in severe pandemic influenza,http://dx.doi.org/10.1186/cc9259,PMC3219262,20840779,CC BY,"INTRODUCTION: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. METHODS: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. RESULTS: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. CONCLUSIONS: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.",2010 Sep 14,"['Bermejo-Martin, Jesus F', 'Martin-Loeches, Ignacio', 'Rello, Jordi', 'Antón, Andres', 'Almansa, Raquel', 'Xu, Luoling', 'Lopez-Campos, Guillermo', 'Pumarola, Tomás', 'Ran, Longsi', 'Ramirez, Paula', 'Banner, David', 'Cheuk Ng, Derek', 'Socias, Lorenzo', 'Loza, Ana', 'Andaluz, David', 'Maravi, Enrique', 'Gómez-Sánchez, Maria J', 'Gordón, Mónica', 'Gallegos, Maria C', 'Fernandez, Victoria', 'Aldunate, Sara', 'León, Cristobal', 'Merino, Pedro', 'Blanco, Jesús', 'Martin-Sanchez, Fernando', 'Rico, Lucia', 'Varillas, David', 'Iglesias, Veronica', 'Marcos, Maria Ángeles', 'Gandía, Francisco', 'Bobillo, Felipe', 'Nogueira, Begoña', 'Rojo, Silvia', 'Resino, Salvador', 'Castro, Carmen', 'Ortiz de Lejarazu, Raul', 'Kelvin, David']",Crit Care,,,False
7518e6365506e35c0e9604339bbf172f3a03c192,PMC,Host adaptive immunity deficiency in severe pandemic influenza,http://dx.doi.org/10.1186/cc9259,PMC3219262,20840779,CC BY,"INTRODUCTION: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. METHODS: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. RESULTS: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. CONCLUSIONS: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.",2010 Sep 14,"['Bermejo-Martin, Jesus F', 'Martin-Loeches, Ignacio', 'Rello, Jordi', 'Antón, Andres', 'Almansa, Raquel', 'Xu, Luoling', 'Lopez-Campos, Guillermo', 'Pumarola, Tomás', 'Ran, Longsi', 'Ramirez, Paula', 'Banner, David', 'Cheuk Ng, Derek', 'Socias, Lorenzo', 'Loza, Ana', 'Andaluz, David', 'Maravi, Enrique', 'Gómez-Sánchez, Maria J', 'Gordón, Mónica', 'Gallegos, Maria C', 'Fernandez, Victoria', 'Aldunate, Sara', 'León, Cristobal', 'Merino, Pedro', 'Blanco, Jesús', 'Martin-Sanchez, Fernando', 'Rico, Lucia', 'Varillas, David', 'Iglesias, Veronica', 'Marcos, Maria Ángeles', 'Gandía, Francisco', 'Bobillo, Felipe', 'Nogueira, Begoña', 'Rojo, Silvia', 'Resino, Salvador', 'Castro, Carmen', 'Ortiz de Lejarazu, Raul', 'Kelvin, David']",Crit Care,,,False
69caf6e8ceedf81348a7833914dd32dfef910640,PMC,Host adaptive immunity deficiency in severe pandemic influenza,http://dx.doi.org/10.1186/cc9259,PMC3219262,20840779,CC BY,"INTRODUCTION: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. METHODS: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. RESULTS: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. CONCLUSIONS: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.",2010 Sep 14,"['Bermejo-Martin, Jesus F', 'Martin-Loeches, Ignacio', 'Rello, Jordi', 'Antón, Andres', 'Almansa, Raquel', 'Xu, Luoling', 'Lopez-Campos, Guillermo', 'Pumarola, Tomás', 'Ran, Longsi', 'Ramirez, Paula', 'Banner, David', 'Cheuk Ng, Derek', 'Socias, Lorenzo', 'Loza, Ana', 'Andaluz, David', 'Maravi, Enrique', 'Gómez-Sánchez, Maria J', 'Gordón, Mónica', 'Gallegos, Maria C', 'Fernandez, Victoria', 'Aldunate, Sara', 'León, Cristobal', 'Merino, Pedro', 'Blanco, Jesús', 'Martin-Sanchez, Fernando', 'Rico, Lucia', 'Varillas, David', 'Iglesias, Veronica', 'Marcos, Maria Ángeles', 'Gandía, Francisco', 'Bobillo, Felipe', 'Nogueira, Begoña', 'Rojo, Silvia', 'Resino, Salvador', 'Castro, Carmen', 'Ortiz de Lejarazu, Raul', 'Kelvin, David']",Crit Care,,,False
b4721d70b699a92030cf67ccbccc44b237b4deed,PMC,Host adaptive immunity deficiency in severe pandemic influenza,http://dx.doi.org/10.1186/cc9259,PMC3219262,20840779,CC BY,"INTRODUCTION: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. METHODS: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. RESULTS: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. CONCLUSIONS: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.",2010 Sep 14,"['Bermejo-Martin, Jesus F', 'Martin-Loeches, Ignacio', 'Rello, Jordi', 'Antón, Andres', 'Almansa, Raquel', 'Xu, Luoling', 'Lopez-Campos, Guillermo', 'Pumarola, Tomás', 'Ran, Longsi', 'Ramirez, Paula', 'Banner, David', 'Cheuk Ng, Derek', 'Socias, Lorenzo', 'Loza, Ana', 'Andaluz, David', 'Maravi, Enrique', 'Gómez-Sánchez, Maria J', 'Gordón, Mónica', 'Gallegos, Maria C', 'Fernandez, Victoria', 'Aldunate, Sara', 'León, Cristobal', 'Merino, Pedro', 'Blanco, Jesús', 'Martin-Sanchez, Fernando', 'Rico, Lucia', 'Varillas, David', 'Iglesias, Veronica', 'Marcos, Maria Ángeles', 'Gandía, Francisco', 'Bobillo, Felipe', 'Nogueira, Begoña', 'Rojo, Silvia', 'Resino, Salvador', 'Castro, Carmen', 'Ortiz de Lejarazu, Raul', 'Kelvin, David']",Crit Care,,,False
6b1db13836f3db30a951ce76759a9bdc522ff1bd,PMC,Host adaptive immunity deficiency in severe pandemic influenza,http://dx.doi.org/10.1186/cc9259,PMC3219262,20840779,CC BY,"INTRODUCTION: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. METHODS: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. RESULTS: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. CONCLUSIONS: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.",2010 Sep 14,"['Bermejo-Martin, Jesus F', 'Martin-Loeches, Ignacio', 'Rello, Jordi', 'Antón, Andres', 'Almansa, Raquel', 'Xu, Luoling', 'Lopez-Campos, Guillermo', 'Pumarola, Tomás', 'Ran, Longsi', 'Ramirez, Paula', 'Banner, David', 'Cheuk Ng, Derek', 'Socias, Lorenzo', 'Loza, Ana', 'Andaluz, David', 'Maravi, Enrique', 'Gómez-Sánchez, Maria J', 'Gordón, Mónica', 'Gallegos, Maria C', 'Fernandez, Victoria', 'Aldunate, Sara', 'León, Cristobal', 'Merino, Pedro', 'Blanco, Jesús', 'Martin-Sanchez, Fernando', 'Rico, Lucia', 'Varillas, David', 'Iglesias, Veronica', 'Marcos, Maria Ángeles', 'Gandía, Francisco', 'Bobillo, Felipe', 'Nogueira, Begoña', 'Rojo, Silvia', 'Resino, Salvador', 'Castro, Carmen', 'Ortiz de Lejarazu, Raul', 'Kelvin, David']",Crit Care,,,False
e65d6ee7efc61bd70cc664b4dca1cdbf635c6b69,PMC,Host adaptive immunity deficiency in severe pandemic influenza,http://dx.doi.org/10.1186/cc9259,PMC3219262,20840779,CC BY,"INTRODUCTION: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. METHODS: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. RESULTS: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. CONCLUSIONS: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.",2010 Sep 14,"['Bermejo-Martin, Jesus F', 'Martin-Loeches, Ignacio', 'Rello, Jordi', 'Antón, Andres', 'Almansa, Raquel', 'Xu, Luoling', 'Lopez-Campos, Guillermo', 'Pumarola, Tomás', 'Ran, Longsi', 'Ramirez, Paula', 'Banner, David', 'Cheuk Ng, Derek', 'Socias, Lorenzo', 'Loza, Ana', 'Andaluz, David', 'Maravi, Enrique', 'Gómez-Sánchez, Maria J', 'Gordón, Mónica', 'Gallegos, Maria C', 'Fernandez, Victoria', 'Aldunate, Sara', 'León, Cristobal', 'Merino, Pedro', 'Blanco, Jesús', 'Martin-Sanchez, Fernando', 'Rico, Lucia', 'Varillas, David', 'Iglesias, Veronica', 'Marcos, Maria Ángeles', 'Gandía, Francisco', 'Bobillo, Felipe', 'Nogueira, Begoña', 'Rojo, Silvia', 'Resino, Salvador', 'Castro, Carmen', 'Ortiz de Lejarazu, Raul', 'Kelvin, David']",Crit Care,,,False
b7cf054fd2a9f9366458e8c251a37bda87fca328,PMC,Effect of Host Species on the Distribution of Mutational Fitness Effects for an RNA Virus,http://dx.doi.org/10.1371/journal.pgen.1002378,PMC3219607,22125497,CC BY,"Knowledge about the distribution of mutational fitness effects (DMFE) is essential for many evolutionary models. In recent years, the properties of the DMFE have been carefully described for some microorganisms. In most cases, however, this information has been obtained only for a single environment, and very few studies have explored the effect that environmental variation may have on the DMFE. Environmental effects are particularly relevant for the evolution of multi-host parasites and thus for the emergence of new pathogens. Here we characterize the DMFE for a collection of twenty single-nucleotide substitution mutants of Tobacco etch potyvirus (TEV) across a set of eight host environments. Five of these host species were naturally infected by TEV, all belonging to family Solanaceae, whereas the other three were partially susceptible hosts belonging to three other plant families. First, we found a significant virus genotype-by-host species interaction, which was sustained by differences in genetic variance for fitness and the pleiotropic effect of mutations among hosts. Second, we found that the DMFEs were markedly different between Solanaceae and non-Solanaceae hosts. Exposure of TEV genotypes to non-Solanaceae hosts led to a large reduction of mean viral fitness, while the variance remained constant and skewness increased towards the right tail. Within the Solanaceae hosts, the distribution contained an excess of deleterious mutations, whereas for the non-Solanaceae the fraction of beneficial mutations was significantly larger. All together, this result suggests that TEV may easily broaden its host range and improve fitness in new hosts, and that knowledge about the DMFE in the natural host does not allow for making predictions about its properties in an alternative host.",2011 Nov 17,"['Lalić, Jasna', 'Cuevas, José M.', 'Elena, Santiago F.']",PLoS Genet,,,True
704a894ab79031263de39fc49d954f7d13aa1bf2,PMC,Prevalence of Korean cats with natural feline coronavirus infections,http://dx.doi.org/10.1186/1743-422X-8-455,PMC3219666,21951835,CC BY,"BACKGROUND: Feline coronavirus is comprised of two pathogenic biotypes consisting of feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV), which are both divided into two serotypes. To examine the prevalence of Korean cats infected with feline coronavirus (FCoV) type I and II, fecal samples were obtained from 212 cats (107 pet and 105 feral) in 2009. RESULTS: Fourteen cats were FCoV-positive, including infections with type I FCoV (n = 8), type II FCoV (n = 4), and types I and II co-infection (n = 2). Low seroprevalences (13.7%, 29/212) of FCoV were identified in chronically ill cats (19.3%, 16/83) and healthy cats (10.1%, 13/129). CONCLUSIONS: Although the prevalence of FCoV infection was not high in comparison to other countries, there was a higher prevalence of type I FCoV in Korean felines. The prevalence of FCoV antigen and antibody in Korean cats are expected to gradually increase due to the rising numbers of stray and companion cats.",2011 Sep 28,"['An, Dong-Jun', 'Jeoung, Hye-Young', 'Jeong, WooSeog', 'Park, Jee-Yong', 'Lee, Myoung-Heon', 'Park, Bong-Kyun']",Virol J,,,True
54774da1d5cb436f9bac63726a08b399b05c6992,PMC,"Metagenomic Analysis of Fever, Thrombocytopenia and Leukopenia Syndrome (FTLS) in Henan Province, China: Discovery of a New Bunyavirus",http://dx.doi.org/10.1371/journal.ppat.1002369,PMC3219706,22114553,CC BY,"Since 2007, many cases of fever, thrombocytopenia and leukopenia syndrome (FTLS) have emerged in Henan Province, China. Patient reports of tick bites suggested that infection could contribute to FTLS. Many tick-transmitted microbial pathogens were tested for by PCR/RT-PCR and/or indirect immunofluorescence assay (IFA). However, only 8% (24/285) of samples collected from 2007 to 2010 tested positive for human granulocytic anaplasmosis (HGA), suggesting that other pathogens could be involved. Here, we used an unbiased metagenomic approach to screen and survey for microbes possibly associated with FTLS. BLASTx analysis of deduced protein sequences revealed that a novel bunyavirus (36% identity to Tehran virus, accession: HQ412604) was present only in sera from FTLS patients. A phylogenetic analysis further showed that, although closely related to Uukuniemi virus of the Phlebovirus genus, this virus was distinct. The candidate virus was examined for association with FTLS among samples collected from Henan province during 2007–2010. RT-PCR, viral cultures, and a seroepidemiologic survey were undertaken. RT-PCR results showed that 223 of 285 (78.24%) acute-phase serum samples contained viral RNA. Of 95 patients for whom paired acute and convalescent sera were available, 73 had serologic evidence of infection, with 52 seroconversions and 21 exhibiting a 4-fold increase in antibody titer to the virus. The new virus was isolated from patient acute-phase serum samples and named Henan Fever Virus (HNF virus). Whole-genome sequencing confirmed that the virus was a novel bunyavirus with genetic similarity to known bunyaviruses, and was most closely related to the Uukuniemi virus (34%, 24%, and 29% of maximum identity, respectively, for segment L, M, S at maximum query coverage). After the release of the GenBank sequences of SFTSV, we found that they were nearly identical (>99% identity). These results show that the novel bunyavirus (HNF virus) is strongly correlated with FTLS.",2011 Nov 17,"['Xu, Bianli', 'Liu, Licheng', 'Huang, Xueyong', 'Ma, Hong', 'Zhang, Yuan', 'Du, Yanhua', 'Wang, Pengzhi', 'Tang, Xiaoyan', 'Wang, Haifeng', 'Kang, Kai', 'Zhang, Shiqiang', 'Zhao, Guohua', 'Wu, Weili', 'Yang, Yinhui', 'Chen, Haomin', 'Mu, Feng', 'Chen, Weijun']",PLoS Pathog,,,True
5016b361dce58077b3d647b0772425e079f98d8d,PMC,Neurons are MHC Class I-Dependent Targets for CD8 T Cells upon Neurotropic Viral Infection,http://dx.doi.org/10.1371/journal.ppat.1002393,PMC3219726,22114563,CC BY,"Following infection of the central nervous system (CNS), the immune system is faced with the challenge of eliminating the pathogen without causing significant damage to neurons, which have limited capacities of renewal. In particular, it was thought that neurons were protected from direct attack by cytotoxic T lymphocytes (CTL) because they do not express major histocompatibility class I (MHC I) molecules, at least at steady state. To date, most of our current knowledge on the specifics of neuron-CTL interaction is based on studies artificially inducing MHC I expression on neurons, loading them with exogenous peptide and applying CTL clones or lines often differentiated in culture. Thus, much remains to be uncovered regarding the modalities of the interaction between infected neurons and antiviral CD8 T cells in the course of a natural disease. Here, we used the model of neuroinflammation caused by neurotropic Borna disease virus (BDV), in which virus-specific CTL have been demonstrated as the main immune effectors triggering disease. We tested the pathogenic properties of brain-isolated CD8 T cells against pure neuronal cultures infected with BDV. We observed that BDV infection of cortical neurons triggered a significant up regulation of MHC I molecules, rendering them susceptible to recognition by antiviral CTL, freshly isolated from the brains of acutely infected rats. Using real-time imaging, we analyzed the spatio-temporal relationships between neurons and CTL. Brain-isolated CTL exhibited a reduced mobility and established stable contacts with BDV-infected neurons, in an antigen- and MHC-dependent manner. This interaction induced rapid morphological changes of the neurons, without immediate killing or impairment of electrical activity. Early signs of neuronal apoptosis were detected only hours after this initial contact. Thus, our results show that infected neurons can be recognized efficiently by brain-isolated antiviral CD8 T cells and uncover the unusual modalities of CTL-induced neuronal damage.",2011 Nov 17,"['Chevalier, Grégoire', 'Suberbielle, Elsa', 'Monnet, Céline', 'Duplan, Valérie', 'Martin-Blondel, Guillaume', 'Farrugia, Fanny', 'Le Masson, Gwendal', 'Liblau, Roland', 'Gonzalez-Dunia, Daniel']",PLoS Pathog,,,True
8abf33baca8c7abbbf6ca5f56b404b79f658dd26,PMC,Calf health from birth to weaning. III. housing and management of calf pneumonia,http://dx.doi.org/10.1186/2046-0481-64-14,PMC3220626,22018053,CC BY,"Calfhood diseases have a major impact on the economic viability of cattle operations. A three part review series has been developed focusing on calf health from birth to weaning. In this paper, the last of the three part series, we review disease prevention and management with particular reference to pneumonia, focusing primarily on the pre-weaned calf. Pneumonia in recently weaned suckler calves is also considered, where the key risk factors are related to the time of weaning. Weaning of the suckler calf is often combined with additional stressors including a change in nutrition, environmental change, transport and painful husbandry procedures (castration, dehorning). The reduction of the cumulative effects of these multiple stressors around the time of weaning together with vaccination programmes (preconditioning) can reduce subsequent morbidity and mortality in the feedlot. In most studies, calves housed individually and calves housed outdoors with shelter, are associated with decreased risk of disease. Even though it poses greater management challenges, successful group housing of calves is possible. Special emphasis should be given to equal age groups and to keeping groups stable once they are formed. The management of pneumonia in calves is reliant on a sound understanding of aetiology, relevant risk factors, and of effective approaches to diagnosis and treatment. Early signs of pneumonia include increased respiratory rate and fever, followed by depression. The single most important factor determining the success of therapy in calves with pneumonia is early onset of treatment, and subsequent adequate duration of treatment. The efficacy and economical viability of vaccination against respiratory disease in calves remains unclear.",2011 Oct 21,"['Lorenz, Ingrid', 'Earley, Bernadette', 'Gilmore, John', 'Hogan, Ian', 'Kennedy, Emer', 'More, Simon J']",Ir Vet J,,,True
c56d753d8b3c0fb68cb1bd22f0b7d10eb3c08e93,PMC,Survival of Influenza A(H1N1) on Materials Found in Households: Implications for Infection Control,http://dx.doi.org/10.1371/journal.pone.0027932,PMC3222642,22132172,CC BY,"BACKGROUND: The majority of influenza transmission occurs in homes, schools and workplaces, where many frequently touched communal items are situated. However the importance of transmission via fomites is unclear since few data exist on the survival of virus on commonly touched surfaces. We therefore measured the viability over time of two H1N1 influenza strains applied to a variety of materials commonly found in households and workplaces. METHODOLOGY AND PRINCIPAL FINDINGS: Influenza A/PuertoRico/8/34 (PR8) or A/Cambridge/AHO4/2009 (pandemic H1N1) viruses were inoculated onto a wide range of surfaces used in home and work environments, then sampled at set times following incubation at stabilised temperature and humidity. Virus genome was measured by RT-PCR; plaque assay (for PR8) or fluorescent focus formation (for pandemic H1N1) was used to assess the survival of viable virus. CONCLUSIONS/SIGNIFICANCE: The genome of either virus could be detected on most surfaces 24 h after application with relatively little drop in copy number, with the exception of unsealed wood surfaces. In contrast, virus viability dropped much more rapidly. Live virus was recovered from most surfaces tested four hours after application and from some non-porous materials after nine hours, but had fallen below the level of detection from all surfaces at 24 h. We conclude that influenza A transmission via fomites is possible but unlikely to occur for long periods after surface contamination (unless re-inoculation occurs). In situations involving a high probability of influenza transmission, our data suggest a hierarchy of priorities for surface decontamination in the multi-surface environments of home and hospitals.",2011 Nov 22,"['Greatorex, Jane S.', 'Digard, Paul', 'Curran, Martin D.', 'Moynihan, Robert', 'Wensley, Harrison', 'Wreghitt, Tim', 'Varsani, Harsha', 'Garcia, Fayna', 'Enstone, Joanne', 'Nguyen-Van-Tam, Jonathan S.']",PLoS One,,,True
6bcf5a5f877be9a08113db6aec4a409f8d111895,PMC,Respiratory failure presenting in H1N1 influenza with Legionnaires disease: two case reports,http://dx.doi.org/10.1186/1752-1947-5-520,PMC3223529,22018019,CC BY,"INTRODUCTION: Media sensationalism on the H1N1 outbreak may have influenced decisional processes and clinical diagnosis. CASE PRESENTATION: We report two cases of patients who presented in 2009 with coexisting H1N1 virus and Legionella infections: a 69-year-old Caucasian man and a 71-year-old Caucasian woman. In our cases all the signs and symptoms, including vomiting, progressive respiratory disease leading to respiratory failure, refractory hypoxemia, leukopenia, lymphopenia, thrombocytopenia, and elevated levels of creatine kinase and hepatic aminotransferases, were consistent with critical illness due to 2009 H1N1 virus infection. Other infectious disorders may mimic H1N1 viral infection especially Legionnaires' disease. Because the swine flu H1N1 pandemic occurred in Autumn in Italy, Legionnaires disease was to be highly suspected since the peak incidence usually occurs in early fall. We do think that our immediate suspicion of Legionella infection based on clinical history and X-ray abnormalities was fundamental for a successful resolution. CONCLUSION: Our two case reports suggest that patients with H1N1 should be screened for Legionella, which is not currently common practice. This is particularly important since the signs and symptoms of both infections are similar.",2011 Oct 21,"['Iannuzzi, Michele', 'De Robertis, Edoardo', 'Piazza, Ornella', 'Rispoli, Fabio', 'Servillo, Giuseppe', 'Tufano, Rosalba']",J Med Case Reports,,,True
8871ee344c8ca239b4aa5077f5e438075663299b,PMC,"Field Epidemiology and Laboratory Training Programs in sub-Saharan Africa from 2004 to 2010: need, the process, and prospects",,PMC3224071,22187606,CC BY,"As of 2010 sub-Saharan Africa had approximately 865 million inhabitants living with numerous public health challenges. Several public health initiatives [e.g., the United States (US) President's Emergency Plan for AIDS Relief and the US President's Malaria Initiative] have been very successful at reducing mortality from priority diseases. A competently trained public health workforce that can operate multi-disease surveillance and response systems is necessary to build upon and sustain these successes and to address other public health problems. Sub-Saharan Africa appears to have weathered the recent global economic downturn remarkably well and its increasing middle class may soon demand stronger public health systems to protect communities. The Epidemic Intelligence Service (EIS) program of the US Centers for Disease Control and Prevention (CDC) has been the backbone of public health surveillance and response in the US during its 60 years of existence. EIS has been adapted internationally to create the Field Epidemiology Training Program (FETP) in several countries. In the 1990s CDC and the Rockefeller Foundation collaborated with the Uganda and Zimbabwe ministries of health and local universities to create 2-year Public Health Schools Without Walls (PHSWOWs) which were based on the FETP model. In 2004 the FETP model was further adapted to create the Field Epidemiology and Laboratory Training Program (FELTP) in Kenya to conduct joint competency-based training for field epidemiologists and public health laboratory scientists providing a master's degree to participants upon completion. The FELTP model has been implemented in several additional countries in sub-Saharan Africa. By the end of 2010 these 10 FELTPs and two PHSWOWs covered 613 million of the 865 million people in sub-Saharan Africa and had enrolled 743 public health professionals. We describe the process that we used to develop 10 FELTPs covering 15 countries in sub-Saharan Africa from 2004 to 2010 as a strategy to develop a locally trained public health workforce that can operate multi-disease surveillance and response systems.",2011 Oct 19,"['Nsubuga, Peter', 'Johnson, Kenneth', 'Tetteh, Christopher', 'Oundo, Joseph', 'Weathers, Andrew', 'Vaughan, James', 'Elbon, Suzanne', 'Tshimanga, Mufuta', 'Ndugulile, Faustine', 'Ohuabunwo, Chima', 'Evering-Watley, Michele', 'Mosha, Fausta', 'Oleribe, Obinna', 'Nguku, Patrick', 'Davis, Lora', 'Preacely, Nykiconia', 'Luce, Richard', 'Antara, Simon', 'Imara, Hiari', 'Ndjakani, Yassa', 'Doyle, Timothy', 'Espinosa, Yescenia', 'Kazambu, Ditu', 'Delissaint, Dieula', 'Ngulefac, John', 'Njenga, Kariuki']",Pan Afr Med J,,,True
360fb902fea73a294614ebd95276b59de868786c,PMC,High success and low mortality rates with non-invasive ventilation in influenza A H1N1 patients in a tertiary hospital,http://dx.doi.org/10.1186/1756-0500-4-375,PMC3224397,21955389,CC BY,"BACKGROUND: In 2009, an outbreak of respiratory illness caused by influenza A H1N1 virus occurred worldwide. Some patients required Intensive Care Unit (ICU) admission. The use of non-invasive ventilation (NIV) in these patients is controversial, as the aerosol dispersion may contaminate the environment and health-care co-workers. METHODS: Describe the respiratory profile, the mortality rate, and the benefit of using NIV in patients with confirmed diagnosis of influenza AH1N1 who were admitted in the ICU during the year 2009. RESULTS: A total of 1, 401 cases of influenza A H1N1 were confirmed in our hospital by real-time RT-PCR in 2009, and 20 patients were admitted to the ICU. The patients' ages ranged from 18 to 74 years (median of 42). Acute Respiratory Failure (ARF) was present in 70% of patients. The median Acute Physiology and Chronic Health Evaluation II score was 7 (range 7 to 25). Of the 14 patients who developed ARF, 85.7% needed NIV and 14% needed invasive MV at admission. Our success rate (41.6%) with NIV was higher than that described by others. The hospital mortality rate was 2.1%. When influenza A H1N1 arrived in Brazil, the disease was already on endemic alert in other countries. The population was already aware of the symptoms and the health-care system of the treatment. This allowed patients to be properly and promptly treated for influenza A H1N1, while health-care workers took protective measures to avoid contamination. CONCLUSION: In our study we found a high success and low mortality rates with non-invasive ventilation in patients with influenza A H1N1.",2011 Sep 28,"['Timenetsky, Karina T', 'Aquino, Silvia HCT', 'Saghabi, Cilene', 'Taniguchi, Corinne', 'Silvia, Claudia V', 'Correa, Luci', 'Marra, Alexandre R', 'Eid, Raquel AC', 'dos Santos, Oscar FP']",BMC Res Notes,,,True
6dbc1181175c5ce84c649469fc4e9a4c7b6b8f32,PMC,Preventing Airborne Disease Transmission: Review of Methods for Ventilation Design in Health Care Facilities,http://dx.doi.org/10.4061/2011/124064,PMC3226423,22162813,CC BY,"Health care facility ventilation design greatly affects disease transmission by aerosols. The desire to control infection in hospitals and at the same time to reduce their carbon footprint motivates the use of unconventional solutions for building design and associated control measures. This paper considers indoor sources and types of infectious aerosols, and pathogen viability and infectivity behaviors in response to environmental conditions. Aerosol dispersion, heat and mass transfer, deposition in the respiratory tract, and infection mechanisms are discussed, with an emphasis on experimental and modeling approaches. Key building design parameters are described that include types of ventilation systems (mixing, displacement, natural and hybrid), air exchange rate, temperature and relative humidity, air flow distribution structure, occupancy, engineered disinfection of air (filtration and UV radiation), and architectural programming (source and activity management) for health care facilities. The paper describes major findings and suggests future research needs in methods for ventilation design of health care facilities to prevent airborne infection risk.",2011 Nov 15,"['Aliabadi, Amir A.', 'Rogak, Steven N.', 'Bartlett, Karen H.', 'Green, Sheldon I.']",Adv Prev Med,,,True
2db670e443cdceb7fb2ff63b6331df5d12efef99,PMC,A Quantitative Method for the Specific Assessment of Caspase-6 Activity in Cell Culture,http://dx.doi.org/10.1371/journal.pone.0027680,PMC3226564,22140457,CC BY,"Aberrant activation of caspase-6 has recently emerged as a major contributor to the pathogeneses of neurodegenerative disorders such as Alzheimer's and Huntington disease. Commercially available assays to measure caspase-6 activity commonly use the VEID peptide as a substrate. However these methods are not well suited to specifically assess caspase-6 activity in the presence of other, confounding protease activities, as often encountered in cell and tissue samples. Here we report the development of a method that overcomes this limitation by using a protein substrate, lamin A, which is highly specific for caspase-6 cleavage at amino acid 230. Using a neo-epitope antibody against cleaved lamin A, we developed an electrochemiluminescence-based ELISA assay that is suitable to specifically detect and quantify caspase-6 activity in highly apoptotic cell extracts. The method is more sensitive than VEID-based assays and can be adapted to a high-content imaging platform for high-throughput screening. This method should be useful to screen for and characterize caspase-6 inhibitor compounds and other interventions to decrease intracellular caspase-6 activity for applications in neurodegenerative disorders.",2011 Nov 29,"['Ehrnhoefer, Dagmar E.', 'Skotte, Niels H.', 'Savill, Jane', 'Nguyen, Yen T. N.', 'Ladha, Safia', 'Cao, Li-Ping', 'Dullaghan, Edie', 'Hayden, Michael R.']",PLoS One,,,True
ea40bddad18086f300f45b71a07f3e4c14e060eb,PMC,Mapping of Minimal Motifs of B-Cell Epitopes on Human Zona Pellucida Glycoprotein-3,http://dx.doi.org/10.1155/2012/831010,PMC3227431,22162720,CC BY,"The human zona pellucida glycoprotein-3 (hZP3) by virtue of its critical role during fertilization has been proposed as a promising candidate antigen to develop a contraceptive vaccine. In this direction, it is imperative to map minimal motifs of the B cell epitopes (BCEs) so as to avoid ZP-specific oophoritogenic T cell epitopes (TCEs) in the ZP3-based immunogens. In this study, based on known results of mapping marmoset and bonnet monkey ZP3 (mstZP3 and bmZP3), two predictable epitopes(23–30  and  301–320) on hZP3 were first confirmed and five minimal motifs within four epitopes on hZP3 were defined using serum to recombinant hZP3a(22–176) or hZP3b(177–348) as well as a biosynthetic peptide strategy. These defined minimal motifs were QPLWLL(23–28) for hZP3(23–30), MQVTDD(103–108) for hZP3(93–110), EENW(178–181) for hZP3(172–190), as well as SNSWF(306–310) and EGP(313–315) for hZP3(301–320), respectively. Furthermore, the antigenicity of two peptides for hZP3(172–187) and hZP3(301–315) and specificity of the antibody response to these peptides were also evaluated, which produced high-titer antibodies in immunized animals that were capable of reacting to ZP on human oocytes, r-hZP3b(177–348) protein, as well as r-hZP3(172–190), r-hZP3(303–310), and r-hZP3(313–320) epitope peptides fused with truncated GST188 protein.",2012 Nov 17,"['Xu, Wan-Xiang', 'He, Ya-Ping', 'Wang, Jian', 'Tang, Hai-Ping', 'Shi, Hui-Juan', 'Sun, Xiao-Xi', 'Ji, Chao-Neng', 'Gu, Shao-Hua', 'Xie, Yi']",Clin Dev Immunol,,,True
6737b541bf9d5d5bbb80cc1dd06456f93dbcda72,PMC,Evolution of the Bovine TLR Gene Family and Member Associations with Mycobacterium avium Subspecies paratuberculosis Infection,http://dx.doi.org/10.1371/journal.pone.0027744,PMC3227585,22164200,CC BY,"Members of the Toll-like receptor (TLR) gene family occupy key roles in the mammalian innate immune system by functioning as sentries for the detection of invading pathogens, thereafter provoking host innate immune responses. We utilized a custom next-generation sequencing approach and allele-specific genotyping assays to detect and validate 280 biallelic variants across all 10 bovine TLR genes, including 71 nonsynonymous single nucleotide polymorphisms (SNPs) and one putative nonsense SNP. Bayesian haplotype reconstructions and median joining networks revealed haplotype sharing between Bos taurus taurus and Bos taurus indicus breeds at every locus, and specialized beef and dairy breeds could not be differentiated despite an average polymorphism density of 1 marker/158 bp. Collectively, 160 tagSNPs and two tag insertion-deletion mutations (indels) were sufficient to predict 100% of the variation at 280 variable sites for both Bos subspecies and their hybrids, whereas 118 tagSNPs and 1 tagIndel predictively captured 100% of the variation at 235 variable sites for B. t. taurus. Polyphen and SIFT analyses of amino acid (AA) replacements encoded by bovine TLR SNPs indicated that up to 32% of the AA substitutions were expected to impact protein function. Classical and newly developed tests of diversity provide strong support for balancing selection operating on TLR3 and TLR8, and purifying selection acting on TLR10. An investigation of the persistence and continuity of linkage disequilibrium (r(2)≥0.50) between adjacent variable sites also supported the presence of selection acting on TLR3 and TLR8. A case-control study employing validated variants from bovine TLR genes recognizing bacterial ligands revealed six SNPs potentially eliciting small effects on susceptibility to Mycobacterium avium spp paratuberculosis infection in dairy cattle. The results of this study will broadly impact domestic cattle research by providing the necessary foundation to explore several avenues of bovine translational genomics, and the potential for marker-assisted vaccination.",2011 Nov 30,"['Fisher, Colleen A.', 'Bhattarai, Eric K.', 'Osterstock, Jason B.', 'Dowd, Scot E.', 'Seabury, Paul M.', 'Vikram, Meenu', 'Whitlock, Robert H.', 'Schukken, Ynte H.', 'Schnabel, Robert D.', 'Taylor, Jeremy F.', 'Womack, James E.', 'Seabury, Christopher M.']",PLoS One,,,True
f56a6e854737649264b48f3709c54551d3660edd,PMC,"A Flavonoid, Luteolin, Cripples HIV-1 by Abrogation of Tat Function",http://dx.doi.org/10.1371/journal.pone.0027915,PMC3227592,22140483,CC BY,"Despite the effectiveness of combination antiretroviral treatment (cART) against HIV-1, evidence indicates that residual infection persists in different cell types. Intensification of cART does not decrease the residual viral load or immune activation. cART restricts the synthesis of infectious virus but does not curtail HIV-1 transcription and translation from either the integrated or unintegrated viral genomes in infected cells. All treated patients with full viral suppression actually have low-level viremia. More than 60% of treated individuals also develop minor HIV-1 –associated neurocognitive deficits (HAND) due to residual virus and immune activation. Thus, new therapeutic agents are needed to curtail HIV-1 transcription and residual virus. In this study, luteolin, a dietary supplement, profoundly reduced HIV-1 infection in reporter cells and primary lymphocytes. HIV-1inhibition by luteolin was independent of viral entry, as shown by the fact that wild-type and VSV–pseudotyped HIV-1 infections were similarly inhibited. Luteolin was unable to inhibit viral reverse transcription. Luteolin had antiviral activity in a latent HIV-1 reactivation model and effectively ablated both clade-B- and -C -Tat-driven LTR transactivation in reporter assays but had no effect on Tat expression and its sub-cellular localization. We conclude that luteolin confers anti–HIV-1 activity at the Tat functional level. Given its biosafety profile and ability to cross the blood-brain barrier, luteolin may serve as a base flavonoid to develop potent anti–HIV-1 derivatives to complement cART.",2011 Nov 30,"['Mehla, Rajeev', 'Bivalkar-Mehla, Shalmali', 'Chauhan, Ashok']",PLoS One,,,True
bcb10d6f9d4c95cfcd762fe6297dcb46bc15ec3f,PMC,Novel Inhibitor Design for Hemagglutinin against H1N1 Influenza Virus by Core Hopping Method,http://dx.doi.org/10.1371/journal.pone.0028111,PMC3227604,22140516,CC BY,"The worldwide spread of H1N1 avian influenza and the increasing reports about its resistance to the current drugs have made a high priority for developing new anti-influenza drugs. Owing to its unique function in assisting viruses to bind the cellular surface, a key step for them to subsequently penetrate into the infected cell, hemagglutinin (HA) has become one of the main targets for drug design against influenza virus. To develop potent HA inhibitors, the ZINC fragment database was searched for finding the optimal compound with the core hopping technique. As a result, the Neo6 compound was obtained. It has been shown through the subsequent molecular docking studies and molecular dynamic simulations that Neo6 not only assumes more favorable conformation at the binding pocket of HA but also has stronger binding interaction with its receptor. Accordingly, Neo6 may become a promising candidate for developing new and more powerful drugs for treating influenza. Or at the very least, the findings reported here may provide useful insights to stimulate new strategy in this area.",2011 Nov 30,"['Li, Xiao-Bo', 'Wang, Shu-Qing', 'Xu, Wei-Ren', 'Wang, Run-Ling', 'Chou, Kuo-Chen']",PLoS One,,,True
d92d00ed95878f5a37061b76e848fda5b11d21da,PMC,"Type I Interferon Reaction to Viral Infection in Interferon-Competent, Immortalized Cell Lines from the African Fruit Bat Eidolon helvum",http://dx.doi.org/10.1371/journal.pone.0028131,PMC3227611,22140523,CC BY,"Bats harbor several highly pathogenic zoonotic viruses including Rabies, Marburg, and henipaviruses, without overt clinical symptoms in the animals. It has been suspected that bats might have evolved particularly effective mechanisms to suppress viral replication. Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E. helvum). Immortalized cell lines were generated; their potential to induce and react on IFN was confirmed, and biological assays were adapted to application in bat cell cultures, enabling comparison of landmark IFN properties with that of common mammalian cell lines. E. helvum cells were fully capable of reacting to viral and artificial IFN stimuli. E. helvum cells showed highest IFN mRNA induction, highly productive IFN protein secretion, and evidence of efficient IFN stimulated gene induction. In an Alphavirus infection model, O'nyong-nyong virus exhibited strong IFN induction but evaded the IFN response by translational rather than transcriptional shutoff, similar to other Alphavirus infections. These novel IFN-competent cell lines will allow comparative research on zoonotic, bat-borne viruses in order to model mechanisms of viral maintenance and emergence in bat reservoirs.",2011 Nov 30,"['Biesold, Susanne E.', 'Ritz, Daniel', 'Gloza-Rausch, Florian', 'Wollny, Robert', 'Drexler, Jan Felix', 'Corman, Victor M.', 'Kalko, Elisabeth K. V.', 'Oppong, Samuel', 'Drosten, Christian', 'Müller, Marcel A.']",PLoS One,,,True
15228615c1656f39a5ec8dcc8bc26ef0371d4040,PMC,Tamiflu-Resistant but HA-Mediated Cell-to-Cell Transmission through Apical Membranes of Cell-Associated Influenza Viruses,http://dx.doi.org/10.1371/journal.pone.0028178,PMC3227662,22140536,CC BY,"The infection of viruses to a neighboring cell is considered to be beneficial in terms of evasion from host anti-virus defense systems. There are two pathways for viral infection to “right next door”: one is the virus transmission through cell-cell fusion by forming syncytium without production of progeny virions, and the other is mediated by virions without virus diffusion, generally designated cell-to-cell transmission. Influenza viruses are believed to be transmitted as cell-free virus from infected cells to uninfected cells. Here, we demonstrated that influenza virus can utilize cell-to-cell transmission pathway through apical membranes, by handover of virions on the surface of an infected cell to adjacent host cells. Live cell imaging techniques showed that a recombinant influenza virus, in which the neuraminidase gene was replaced with the green fluorescence protein gene, spreads from an infected cell to adjacent cells forming infected cell clusters. This type of virus spreading requires HA activation by protease treatment. The cell-to-cell transmission was also blocked by amantadine, which inhibits the acidification of endosomes required for uncoating of influenza virus particles in endosomes, indicating that functional hemagglutinin and endosome acidification by M2 ion channel were essential for the cell-to-cell influenza virus transmission. Furthermore, in the cell-to-cell transmission of influenza virus, progeny virions could remain associated with the surface of infected cell even after budding, for the progeny virions to be passed on to adjacent uninfected cells. The evidence that cell-to-cell transmission occurs in influenza virus lead to the caution that local infection proceeds even when treated with neuraminidase inhibitors.",2011 Nov 30,"['Mori, Kotaro', 'Haruyama, Takahiro', 'Nagata, Kyosuke']",PLoS One,,,True
af06f5132b3178795ba440ec4f4949e9008c1737,PMC,It Takes a Community to Raise the Prevalence of a Zoonotic Pathogen,http://dx.doi.org/10.1155/2011/741406,PMC3228346,22162687,CC BY,"By definition, zoonotic pathogens are not strict host-species specialists in that they infect humans and at least one nonhuman reservoir species. The majority of zoonotic pathogens infect and are amplified by multiple vertebrate species in nature, each of which has a quantitatively different impact on the distribution and abundance of the pathogen and thus on disease risk. Unfortunately, when new zoonotic pathogens emerge, the dominant response by public health scientists is to search for a few, or even the single, most important reservoirs and to ignore other species that might strongly influence transmission. This focus on the single “primary” reservoir host species can delay biological understanding, and potentially public health interventions as species important in either amplifying or regulating the pathogen are overlooked. Investigating the evolutionary and ecological strategy of newly discovered or emerging pathogens within the community of potential and actual host species will be fruitful to both biological understanding and public health.",2011 Nov 21,"['Brisson, Dustin', 'Brinkley, Catherine', 'Humphrey, Parris T.', 'Kemps, Brian D.', 'Ostfeld, Richard S.']",Interdiscip Perspect Infect Dis,,,True
fbf1ce71db9a70babb5b4902d23438c1956125c6,PMC,Yeast Based Small Molecule Screen for Inhibitors of SARS-CoV,http://dx.doi.org/10.1371/journal.pone.0028479,PMC3229576,22164298,CC BY,"Severe acute respiratory coronavirus (SARS-CoV) emerged in 2002, resulting in roughly 8000 cases worldwide and 10% mortality. The animal reservoirs for SARS-CoV precursors still exist and the likelihood of future outbreaks in the human population is high. The SARS-CoV papain-like protease (PLP) is an attractive target for pharmaceutical development because it is essential for virus replication and is conserved among human coronaviruses. A yeast-based assay was established for PLP activity that relies on the ability of PLP to induce a pronounced slow-growth phenotype when expressed in S. cerevisiae. Induction of the slow-growth phenotype was shown to take place over a 60-hour time course, providing the basis for conducting a screen for small molecules that restore growth by inhibiting the function of PLP. Five chemical suppressors of the slow-growth phenotype were identified from the 2000 member NIH Diversity Set library. One of these, NSC158362, potently inhibited SARS-CoV replication in cell culture without toxic effects on cells, and it specifically inhibited SARS-CoV replication but not influenza virus replication. The effect of NSC158362 on PLP protease, deubiquitinase and anti-interferon activities was investigated but the compound did not alter these activities. Another suppressor, NSC158011, demonstrated the ability to inhibit PLP protease activity in a cell-based assay. The identification of these inhibitors demonstrated a strong functional connection between the PLP-based yeast assay, the inhibitory compounds, and SARS-CoV biology. Furthermore the data with NSC158362 suggest a novel mechanism for inhibition of SARS-CoV replication that may involve an unknown activity of PLP, or alternatively a direct effect on a cellular target that modifies or bypasses PLP function in yeast and mammalian cells.",2011 Dec 2,"['Frieman, Matthew', 'Basu, Dipanwita', 'Matthews, Krystal', 'Taylor, Justin', 'Jones, Grant', 'Pickles, Raymond', 'Baric, Ralph', 'Engel, Daniel A.']",PLoS One,,,True
a5df67ac88dab77c50c138cec2944814000c859f,PMC,Changes of Adult Population Health Status in China from 2003 to 2008,http://dx.doi.org/10.1371/journal.pone.0028411,PMC3229585,22164286,CC BY,"OBJECTIVES: The purpose of this study was to examine the change in health status of China's adult population between the years of 2003 and 2008 due to rapid economic growth and medical system improvement. METHODS: Data from the third and fourth Chinese national health services surveys covering 141,927 residents in 2003 and 136,371 residents in 2008 who were aged >18 years were analyzed. RESULTS: Chinese respondents in 2008 were more likely to report disease than in 2003. Smoking slightly decreased among men and women, and regular exercise showed much improvement. Stratified analyses revealed significant subpopulation disparities in rate ratios for 2008/2003 in the presence of chronic disease, with greater increases among women, elderly, the Han nationality, unmarried and widow, illiterate, rural, and regions east of China than other groups. CONCLUSIONS: Chinese adults in 2008 had worse health status than in 2003 in terms of presence of chronic disease. China's reform of health care will face more complex challenges in coming years from the deteriorating health status in Chinese adults.",2011 Dec 2,"['Sun, Hongpeng', 'Zhang, Qiuju', 'Luo, Xiao', 'Quan, Hude', 'Zhang, Feng', 'Liu, Chang', 'Liu, Meina']",PLoS One,,,True
523d27d193f6bd636b6fae4da4af51ea66907772,PMC,Persistent Expression of Hepatitis C Virus Non-Structural Proteins Leads to Increased Autophagy and Mitochondrial Injury in Human Hepatoma Cells,http://dx.doi.org/10.1371/journal.pone.0028551,PMC3229600,22164304,CC0,"HCV infection is a major cause of chronic liver disease and liver cancer in the United States. To address the pathogenesis caused by HCV infection, recent studies have focused on the direct cytopathic effects of individual HCV proteins, with the objective of identifying their specific roles in the overall pathogenesis. However, this approach precludes examination of the possible interactions between different HCV proteins and organelles. To obtain a better understanding of the various cytopathic effects of and cellular responses to HCV proteins, we used human hepatoma cells constitutively replicating HCV RNA encoding either the full-length polyprotein or the non-structural proteins, or cells constitutively expressing the structural protein core, to model the state of persistent HCV infection and examined the combination of various HCV proteins in cellular pathogenesis. Increased reactive oxygen species (ROS) generation in the mitochondria, mitochondrial injury and degeneration, and increased lipid accumulation were common among all HCV protein-expressing cells regardless of whether they expressed the structural or non-structural proteins. Expression of the non-structural proteins also led to increased oxidative stress in the cytosol, membrane blebbing in the endoplasmic reticulum, and accumulation of autophagocytic vacuoles. Alterations of cellular redox state, on the other hand, significantly changed the level of autophagy, suggesting a direct link between oxidative stress and HCV-mediated activation of autophagy. With the wide-spread cytopathic effects, cells with the full-length HCV polyprotein showed a modest antioxidant response and exhibited a significant increase in population doubling time and a concomitant decrease in cyclin D1. In contrast, cells expressing the non-structural proteins were able to launch a vigorous antioxidant response with up-regulation of antioxidant enzymes. The population doubling time and cyclin D1 level were also comparable to that of control cells. Finally, the cytopathic effects of core protein appeared to focus on the mitochondria without remarkable disturbances in the cytosol.",2011 Dec 2,"['Chu, Victor C.', 'Bhattacharya, Sayanti', 'Nomoto, Ann', 'Lin, Jiahui', 'Zaidi, Syed Kashif', 'Oberley, Terry D.', 'Weinman, Steven A.', 'Azhar, Salman', 'Huang, Ting-Ting']",PLoS One,,,True
9f5eb4cb37108793e2cf0ed3d5a68fea14620866,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,True
85445df68b35ea6813e73f82cf25be0e79f85984,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
c3b36cbef6bc5cbbd9ca8a7ce0d8581a3f7788c3,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,True
629da5ea7026f4f1a92b1a1bb0d2c2716e96ee57,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
9effda40334841573b2aa2600f56566a9faf71ff,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,True
e1a16106b7ace2c22c2958ba90cfe498efb9c509,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
7d0371cd505199c4f4f76e8884fcaf010a7fe3db,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
d96705b398373bfe34e6c4485a8482d89e37ff67,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
186bec5297ab7757c48f921af2ef1ae9f06780c3,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
0bd435718fed48d151e100eb0fc731d02c0adab6,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
e7358ff1cbb991ea673ffcd3ad13f067cc0fbb15,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
cea092fa779215010c8fafededcb5fab2b435a89,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
59c932b49a6498b87e3d43f42038cef789094b4d,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
03a9435da640ba52544a7b843acc359d3d98044e,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
a5bb10a841381a8c460e9127f0d66cbdf4f15248,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
7f1f94a49e088244c897fd0bfc96de817d1b804a,PMC,Characterization of spontaneously generated prion-like conformers in cultured cells,,PMC3229973,21990137,CC BY,"A distinct conformational transition from the α-helix-rich cellular prion protein (PrP(C)) into its β-sheet-rich pathological isoform (PrP(Sc)) is the hallmark of prion diseases, a group of fatal transmissible encephalopathies that includes spontaneous and acquired forms. Recently, a PrP(Sc)-like intermediate form characterized by the formation of insoluble aggregates and protease-resistant PrP species termed insoluble PrP(C) (iPrP(C)) has been identified in uninfected mammalian brains and cultured neuronal cells, providing new insights into the molecular mechanism(s) of these diseases. Here, we explore the molecular characteristics of the spontaneously formed iPrP(C) in cultured neuroblastoma cells expressing wild-type or mutant human PrP linked to two familial prion diseases. We observed that although PrP mutation at either residue 183 from Thr to Ala (PrP(T183A)) or at residue 198 from Phe to Ser (PrP(F198S)) affects glycosylation at both N-linked glycosylation sites, the T183A mutation that results in intracellular retention significantly increased the formation of iPrP(C). Moreover, while autophagy is increased in F198S cells, it was significantly decreased in T183A cells. Our results indicate that iPrP(C) may be formed more readily in an intracellular compartment and that a significant increase in PrP(T183A) aggregation may be attributable to the inhibition of autophagy.",2011 Oct 9,"['Zou, Roger S.', 'Fujioka, Hisashi', 'Guo, Jian-Ping', 'Xiao, Xiangzhu', 'Shimoji, Miyuki', 'Kong, Crystal', 'Chen, Cecilia', 'Tasnadi, Megan', 'Voma, Chesinta', 'Yuan, Jue', 'Moudjou, Mohammed', 'Laude, Hubert', 'Petersen, Robert B.', 'Zou, Wen-Quan']",Aging (Albany NY),,,True
4aa19640fd1b1a8fc71b31d32fe6009c992bd767,PMC,Inhibition of Interferon Induction and Action by the Nairovirus Nairobi Sheep Disease Virus/Ganjam Virus,http://dx.doi.org/10.1371/journal.pone.0028594,PMC3230622,22163042,CC BY,"The Nairoviruses are an important group of tick-borne viruses that includes pathogens of man (Crimean Congo hemorrhagic fever virus) and livestock animals (Dugbe virus, Nairobi sheep disease virus (NSDV)). NSDV is found in large parts of East Africa and the Indian subcontinent (where it is known as Ganjam virus). We have investigated the ability of NSDV to antagonise the induction and actions of interferon. Both pathogenic and apathogenic isolates could actively inhibit the induction of type 1 interferon, and also blocked the signalling pathways of both type 1 and type 2 interferons. Using transient expression of viral proteins or sections of viral proteins, these activities all mapped to the ovarian tumour-like protease domain (OTU) found in the viral RNA polymerase. Virus infection, or expression of this OTU domain in transfected cells, led to a great reduction in the incorporation of ubiquitin or ISG15 protein into host cell proteins. Point mutations in the OTU that inhibited the protease activity also prevented it from antagonising interferon induction and action. Interestingly, a mutation at a peripheral site, which had little apparent effect on the ability of the OTU to inhibit ubiquitination and ISG15ylation, removed the ability of the OTU to block the induction of type 1 and the action of type 2 interferons, but had a lesser effect on the ability to block type 1 interferon action, suggesting that targets other than ubiquitin and ISG15 may be involved in the actions of the viral OTU.",2011 Dec 5,"['Holzer, Barbara', 'Bakshi, Siddharth', 'Bridgen, Anne', 'Baron, Michael D.']",PLoS One,,,True
ab15d5ebce1f5f7cf0e689d32a55701e9e8fcde3,PMC,A Human Monoclonal Antibody with Neutralizing Activity against Highly Divergent Influenza Subtypes,http://dx.doi.org/10.1371/journal.pone.0028001,PMC3230632,22162996,CC0,"The interest in broad-range anti-influenza A monoclonal antibodies (mAbs) has recently been strengthened by the identification of anti-hemagglutinin (HA) mAbs endowed with heterosubtypic neutralizing activity to be used in the design of “universal” prophylactic or therapeutic tools. However, the majority of the single mAbs described to date do not bind and neutralize viral isolates belonging to highly divergent subtypes clustering into the two different HA-based influenza phylogenetic groups: the group 1 including, among others, subtypes H1, H2, H5 and H9 and the group 2 including, among others, H3 subtype. Here, we describe a human mAb, named PN-SIA28, capable of binding and neutralizing all tested isolates belonging to phylogenetic group 1, including H1N1, H2N2, H5N1 and H9N2 subtypes and several isolates belonging to group 2, including H3N2 isolates from the first period of the 1968 pandemic. Therefore, PN-SIA28 is capable of neutralizing isolates belonging to subtypes responsible of all the reported pandemics, as well as other subtypes with pandemic potential. The region recognized by PN-SIA28 has been identified on the stem region of HA and includes residues highly conserved among the different influenza subtypes. A deep characterization of PN-SIA28 features may represent a useful help in the improvement of available anti-influenza therapeutic strategies and can provide new tools for the development of universal vaccinal strategies.",2011 Dec 5,"['Clementi, Nicola', 'De Marco, Donata', 'Mancini, Nicasio', 'Solforosi, Laura', 'Moreno, Guisella J.', 'Gubareva, Larisa V.', 'Mishin, Vasiliy', 'Di Pietro, Andrea', 'Vicenzi, Elisa', 'Siccardi, Antonio G.', 'Clementi, Massimo', 'Burioni, Roberto']",PLoS One,,,True
b61d4d87ea3b4fa2ff058ee867bdac4f15c0cf11,PMC,Stress Granules in the Viral Replication Cycle,http://dx.doi.org/10.3390/v3112328,PMC3230854,22163347,CC BY,"As intracellular parasites, viruses require a host cell in order to replicate. However, they face a series of cellular responses against infection. One of these responses is the activation of the double-stranded RNA (dsRNA)-activated protein kinase R (PKR). PKR phosphorylates the α subunit of eukaryotic translation initiation factor 2 (eIF2α), which in turn results in global protein synthesis inhibition and formation of stress granules (SGs). Recent studies have shown that SGs can interfere with the replicative cycle of certain viruses. This review addresses how viruses have evolved different control strategies at the SG level to ensure an efficient replication cycle during the cellular stress response triggered by the viral infection.",2011 Nov 18,"['Montero, Hilda', 'Trujillo-Alonso, Vicenta']",Viruses,,,True
c7fbc3c2ef9549d8a6531237b2e9d09cf09a6567,PMC,Microfluidics-Based Lab-on-Chip Systems in DNA-Based Biosensing: An Overview,http://dx.doi.org/10.3390/s110605754,PMC3231440,22163925,CC BY,"Microfluidics-based lab-on-chip (LOC) systems are an active research area that is revolutionising high-throughput sequencing for the fast, sensitive and accurate detection of a variety of pathogens. LOCs also serve as portable diagnostic tools. The devices provide optimum control of nanolitre volumes of fluids and integrate various bioassay operations that allow the devices to rapidly sense pathogenic threat agents for environmental monitoring. LOC systems, such as microfluidic biochips, offer advantages compared to conventional identification procedures that are tedious, expensive and time consuming. This paper aims to provide a broad overview of the need for devices that are easy to operate, sensitive, fast, portable and sufficiently reliable to be used as complementary tools for the control of pathogenic agents that damage the environment.",2011 May 27,"['Dutse, Sabo Wada', 'Yusof, Nor Azah']",Sensors (Basel),,,True
2f855365da2675234802a5f218bda88aacc089b7,PMC,Lactococci and lactobacilli as mucosal delivery vectors for therapeutic proteins and DNA vaccines,http://dx.doi.org/10.1186/1475-2859-10-S1-S4,PMC3231930,21995317,CC BY,"Food-grade Lactic Acid Bacteria (LAB) have been safely consumed for centuries by humans in fermented foods. Thus, they are good candidates to develop novel oral vectors, constituting attractive alternatives to attenuated pathogens, for mucosal delivery strategies. Herein, this review summarizes our research, up until now, on the use of LAB as mucosal delivery vectors for therapeutic proteins and DNA vaccines. Most of our work has been based on the model LAB Lactococcus lactis, for which we have developed efficient genetic tools, including expression signals and host strains, for the heterologous expression of therapeutic proteins such as antigens, cytokines and enzymes. Resulting recombinant lactococci strains have been tested successfully for their prophylactic and therapeutic effects in different animal models: i) against human papillomavirus type 16 (HPV-16)-induced tumors in mice, ii) to partially prevent a bovine β-lactoglobulin (BLG)-allergic reaction in mice and iii) to regulate body weight and food consumption in obese mice. Strikingly, all of these tools have been successfully transposed to the Lactobacillus genus, in recent years, within our laboratory. Notably, anti-oxidative Lactobacillus casei strains were constructed and tested in two chemically-induced colitis models. In parallel, we also developed a strategy based on the use of L. lactis to deliver DNA at the mucosal level, and were able to show that L. lactis is able to modulate the host response through DNA delivery. Today, we consider that all of our consistent data, together with those obtained by other groups, demonstrate and reinforce the interest of using LAB, particularly lactococci and lactobacilli strains, to develop novel therapeutic protein mucosal delivery vectors which should be tested now in human clinical trials.",2011 Aug 30,"['Bermúdez-Humarán, Luis G', 'Kharrat, Pascale', 'Chatel, Jean-Marc', 'Langella, Philippe']",Microb Cell Fact,,,True
f18afbc0a4621e7f13dcfbc67c85bf8dfe3b30ea,PMC,Tissue Tropism and Target Cells of NSs-Deleted Rift Valley Fever Virus in Live Immunodeficient Mice,http://dx.doi.org/10.1371/journal.pntd.0001421,PMC3232203,22163058,CC BY,"BACKGROUND: Rift Valley fever virus (RVFV) causes disease in livestock and humans. It can be transmitted by mosquitoes, inhalation or physical contact with the body fluids of infected animals. Severe clinical cases are characterized by acute hepatitis with hemorrhage, meningoencephalitis and/or retinitis. The dynamics of RVFV infection and the cell types infected in vivo are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: RVFV strains expressing humanized Renilla luciferase (hRLuc) or green fluorescent protein (GFP) were generated and inoculated to susceptible Ifnar1-deficient mice. We investigated the tissue tropism in these mice and the nature of the target cells in vivo using whole-organ imaging and flow cytometry. After intraperitoneal inoculation, hRLuc signal was observed primarily in the thymus, spleen and liver. Macrophages infiltrating various tissues, in particular the adipose tissue surrounding the pancreas also expressed the virus. The liver rapidly turned into the major luminescent organ and the mice succumbed to severe hepatitis. The brain remained weakly luminescent throughout infection. FACS analysis in RVFV-GFP-infected mice showed that the macrophages, dendritic cells and granulocytes were main target cells for RVFV. The crucial role of cells of the monocyte/macrophage/dendritic lineage during RVFV infection was confirmed by the slower viral dissemination, decrease in RVFV titers in blood, and prolonged survival of macrophage- and dendritic cell-depleted mice following treatment with clodronate liposomes. Upon dermal and nasal inoculations, the viral dissemination was primarily observed in the lymph node draining the injected ear and in the lungs respectively, with a significant increase in survival time. CONCLUSIONS/SIGNIFICANCE: These findings reveal the high levels of phagocytic cells harboring RVFV during viral infection in Ifnar1-deficient mice. They demonstrate that bioluminescent and fluorescent viruses can shed new light into the pathogenesis of RVFV infection.",2011 Dec 6,"['Gommet, Céline', 'Billecocq, Agnès', 'Jouvion, Grégory', 'Hasan, Milena', 'Zaverucha do Valle, Tânia', 'Guillemot, Laurent', 'Blanchet, Charlène', 'van Rooijen, Nico', 'Montagutelli, Xavier', 'Bouloy, Michèle', 'Panthier, Jean-Jacques']",PLoS Negl Trop Dis,,,True
3ea132bf32c7717caf9e57fd48e116eed79697b1,PMC,Phages Bearing Affinity Peptides to Bovine Rotavirus Differentiate the Virus from Other Viruses,http://dx.doi.org/10.1371/journal.pone.0028667,PMC3232237,22163050,CC BY,"The aim of this study was to identify potential ligands and develop a novel diagnostic test to pathogenic bovine rotavirus (BRV) using phage display technology. The viruses were used as an immobilized target followed by incubation with a 12-mer phage display random peptide library. After five rounds of biopanning, phages had a specific binding activity to BRV were isolated. DNA sequencing indicated that phage displayed peptides HVHPPLRPHSDK, HATNHLPTPHNR or YPTHHAHTTPVR were potential ligands to BRV. Using the specific peptide-expressing phages, we developed a phage-based ELISA to differentiate BRV from other viruses. Compared with quantitative real-time PCR (qPCR), the phage-mediated ELISA was more suitable for the capture of BRV and the detection limitation of this approach was 0.1 µg/ml of samples. The high sensitivity, specificity and low cross-reactivity for the phage-based ELISA were confirmed in receiver operating characteristics (ROC) analysis.",2011 Dec 6,"['Wang, Xin', 'Li, Guangxing', 'Ren, Yudong', 'Ren, Xiaofeng']",PLoS One,,,True
cd21b40d05f66d9cc280d65928651c4552ad8fdd,PMC,Evaluation of Internal Reference Genes for Quantitative Expression Analysis by Real-Time PCR in Ovine Whole Blood,http://dx.doi.org/10.3390/ijms12117732,PMC3233434,22174628,CC BY,"The use of reference genes is commonly accepted as the most reliable approach to normalize qRT-PCR and to reduce possible errors in the quantification of gene expression. The most suitable reference genes in sheep have been identified for a restricted range of tissues, but no specific data on whole blood are available. The aim of this study was to identify a set of reference genes for normalizing qRT-PCR from ovine whole blood. We designed 11 PCR assays for commonly employed reference genes belonging to various functional classes and then determined their expression stability in whole blood samples from control and disease-stressed sheep. SDHA and YWHAZ were considered the most suitable internal controls as they were stably expressed regardless of disease status according to both geNorm and NormFinder software; furthermore, geNorm indicated SDHA/HPRT, YWHAZ/GAPDH and SDHA/YWHAZ as the best reference gene combinations in control, disease-stressed and combined sheep groups, respectively. Our study provides a validated panel of optimal control genes which may be useful for the identification of genes differentially expressed by qRT-PCR in a readily accessible tissue, with potential for discovering new physiological and disease markers and as a tool to improve production traits (e.g., by identifying expression Quantitative Trait Loci). An additional outcome of the study is a set of intron-spanning primer sequences suitable for gene expression experiments employing SYBR Green chemistry on other ovine tissues and cells.",2011 Nov 9,"['Peletto, Simone', 'Bertuzzi, Simone', 'Campanella, Chiara', 'Modesto, Paola', 'Maniaci, Maria Grazia', 'Bellino, Claudio', 'Ariello, Dario', 'Quasso, Antonio', 'Caramelli, Maria', 'Acutis, Pier Luigi']",Int J Mol Sci,,,True
c3c131a47ced4db370181524292fac5627fb6389,PMC,Applications of Next-Generation Sequencing Technologies to Diagnostic Virology,http://dx.doi.org/10.3390/ijms12117861,PMC3233444,22174638,CC BY,"Novel DNA sequencing techniques, referred to as “next-generation” sequencing (NGS), provide high speed and throughput that can produce an enormous volume of sequences with many possible applications in research and diagnostic settings. In this article, we provide an overview of the many applications of NGS in diagnostic virology. NGS techniques have been used for high-throughput whole viral genome sequencing, such as sequencing of new influenza viruses, for detection of viral genome variability and evolution within the host, such as investigation of human immunodeficiency virus and human hepatitis C virus quasispecies, and monitoring of low-abundance antiviral drug-resistance mutations. NGS techniques have been applied to metagenomics-based strategies for the detection of unexpected disease-associated viruses and for the discovery of novel human viruses, including cancer-related viruses. Finally, the human virome in healthy and disease conditions has been described by NGS-based metagenomics.",2011 Nov 14,"['Barzon, Luisa', 'Lavezzo, Enrico', 'Militello, Valentina', 'Toppo, Stefano', 'Palù, Giorgio']",Int J Mol Sci,,,True
58d91841094c91e8269b22337c66dfa16e04b965,PMC,Norovirus Regulation of the Innate Immune Response and Apoptosis Occurs via the Product of the Alternative Open Reading Frame 4,http://dx.doi.org/10.1371/journal.ppat.1002413,PMC3234229,22174679,CC BY,"Small RNA viruses have evolved many mechanisms to increase the capacity of their short genomes. Here we describe the identification and characterization of a novel open reading frame (ORF4) encoded by the murine norovirus (MNV) subgenomic RNA, in an alternative reading frame overlapping the VP1 coding region. ORF4 is translated during virus infection and the resultant protein localizes predominantly to the mitochondria. Using reverse genetics we demonstrated that expression of ORF4 is not required for virus replication in tissue culture but its loss results in a fitness cost since viruses lacking the ability to express ORF4 restore expression upon repeated passage in tissue culture. Functional analysis indicated that the protein produced from ORF4 antagonizes the innate immune response to infection by delaying the upregulation of a number of cellular genes activated by the innate pathway, including IFN-Beta. Apoptosis in the RAW264.7 macrophage cell line was also increased during virus infection in the absence of ORF4 expression. In vivo analysis of the WT and mutant virus lacking the ability to express ORF4 demonstrated an important role for ORF4 expression in infection and virulence. STAT1-/- mice infected with a virus lacking the ability to express ORF4 showed a delay in the onset of clinical signs when compared to mice infected with WT virus. Quantitative PCR and histopathological analysis of samples from these infected mice demonstrated that infection with a virus not expressing ORF4 results in a delayed infection in this system. In light of these findings we propose the name virulence factor 1, VF1 for this protein. The identification of VF1 represents the first characterization of an alternative open reading frame protein for the calicivirus family. The immune regulatory function of the MNV VF1 protein provide important perspectives for future research into norovirus biology and pathogenesis.",2011 Dec 8,"['McFadden, Nora', 'Bailey, Dalan', 'Carrara, Guia', 'Benson, Alicia', 'Chaudhry, Yasmin', 'Shortland, Amita', 'Heeney, Jonathan', 'Yarovinsky, Felix', 'Simmonds, Peter', 'Macdonald, Andrew', 'Goodfellow, Ian']",PLoS Pathog,,,True
3e3925148a778080ac13f3f532ee63ae24a3d1e5,PMC,Sequential Adaptive Mutations Enhance Efficient Vector Switching by Chikungunya Virus and Its Epidemic Emergence,http://dx.doi.org/10.1371/journal.ppat.1002412,PMC3234230,22174678,CC BY,"The adaptation of Chikungunya virus (CHIKV) to a new vector, the Aedes albopictus mosquito, is a major factor contributing to its ongoing re-emergence in a series of large-scale epidemics of arthritic disease in many parts of the world since 2004. Although the initial step of CHIKV adaptation to A. albopictus was determined to involve an A226V amino acid substitution in the E1 envelope glycoprotein that first arose in 2005, little attention has been paid to subsequent CHIKV evolution after this adaptive mutation was convergently selected in several geographic locations. To determine whether selection of second-step adaptive mutations in CHIKV or other arthropod-borne viruses occurs in nature, we tested the effect of an additional envelope glycoprotein amino acid change identified in Kerala, India in 2009. This substitution, E2-L210Q, caused a significant increase in the ability of CHIKV to develop a disseminated infection in A. albopictus, but had no effect on CHIKV fitness in the alternative mosquito vector, A. aegypti, or in vertebrate cell lines. Using infectious viruses or virus-like replicon particles expressing the E2-210Q and E2-210L residues, we determined that E2-L210Q acts primarily at the level of infection of A. albopictus midgut epithelial cells. In addition, we observed that the initial adaptive substitution, E1-A226V, had a significantly stronger effect on CHIKV fitness in A. albopictus than E2-L210Q, thus explaining the observed time differences required for selective sweeps of these mutations in nature. These results indicate that the continuous CHIKV circulation in an A. albopictus-human cycle since 2005 has resulted in the selection of an additional, second-step mutation that may facilitate even more efficient virus circulation and persistence in endemic areas, further increasing the risk of more severe and expanded CHIK epidemics.",2011 Dec 8,"['Tsetsarkin, Konstantin A.', 'Weaver, Scott C.']",PLoS Pathog,,,True
8792b598db3c64a2da937a9cefc989a7fd0a67aa,PMC,Multifaceted Regulation of Translational Readthrough by RNA Replication Elements in a Tombusvirus,http://dx.doi.org/10.1371/journal.ppat.1002423,PMC3234231,22174683,CC BY,"Translational readthrough of stop codons by ribosomes is a recoding event used by a variety of viruses, including plus-strand RNA tombusviruses. Translation of the viral RNA-dependent RNA polymerase (RdRp) in tombusviruses is mediated using this strategy and we have investigated this process using a variety of in vitro and in vivo approaches. Our results indicate that readthrough generating the RdRp requires a novel long-range RNA-RNA interaction, spanning a distance of ∼3.5 kb, which occurs between a large RNA stem-loop located 3'-proximal to the stop codon and an RNA replication structure termed RIV at the 3'-end of the viral genome. Interestingly, this long-distance RNA-RNA interaction is modulated by mutually-exclusive RNA structures in RIV that represent a type of RNA switch. Moreover, a different long-range RNA-RNA interaction that was previously shown to be necessary for viral RNA replicase assembly was also required for efficient readthrough production of the RdRp. Accordingly, multiple replication-associated RNA elements are involved in modulating the readthrough event in tombusviruses and we propose an integrated mechanistic model to describe how this regulatory network could be advantageous by (i) providing a quality control system for culling truncated viral genomes at an early stage in the replication process, (ii) mediating cis-preferential replication of viral genomes, and (iii) coordinating translational readthrough of the RdRp with viral genome replication. Based on comparative sequence analysis and experimental data, basic elements of this regulatory model extend to other members of Tombusviridae, as well as to viruses outside of this family.",2011 Dec 8,"['Cimino, Peter A.', 'Nicholson, Beth L.', 'Wu, Baodong', 'Xu, Wei', 'White, K. Andrew']",PLoS Pathog,,,True
5620946d8f3bbeeed801a931baa135ee4dd65176,PMC,SARS Coronavirus nsp1 Protein Induces Template-Dependent Endonucleolytic Cleavage of mRNAs: Viral mRNAs Are Resistant to nsp1-Induced RNA Cleavage,http://dx.doi.org/10.1371/journal.ppat.1002433,PMC3234236,22174690,CC BY,"SARS coronavirus (SCoV) nonstructural protein (nsp) 1, a potent inhibitor of host gene expression, possesses a unique mode of action: it binds to 40S ribosomes to inactivate their translation functions and induces host mRNA degradation. Our previous study demonstrated that nsp1 induces RNA modification near the 5′-end of a reporter mRNA having a short 5′ untranslated region and RNA cleavage in the encephalomyocarditis virus internal ribosome entry site (IRES) region of a dicistronic RNA template, but not in those IRES elements from hepatitis C or cricket paralysis viruses. By using primarily cell-free, in vitro translation systems, the present study revealed that the nsp1 induced endonucleolytic RNA cleavage mainly near the 5′ untranslated region of capped mRNA templates. Experiments using dicistronic mRNAs carrying different IRESes showed that nsp1 induced endonucleolytic RNA cleavage within the ribosome loading region of type I and type II picornavirus IRES elements, but not that of classical swine fever virus IRES, which is characterized as a hepatitis C virus-like IRES. The nsp1-induced RNA cleavage of template mRNAs exhibited no apparent preference for a specific nucleotide sequence at the RNA cleavage sites. Remarkably, SCoV mRNAs, which have a 5′ cap structure and 3′ poly A tail like those of typical host mRNAs, were not susceptible to nsp1-mediated RNA cleavage and importantly, the presence of the 5′-end leader sequence protected the SCoV mRNAs from nsp1-induced endonucleolytic RNA cleavage. The escape of viral mRNAs from nsp1-induced RNA cleavage may be an important strategy by which the virus circumvents the action of nsp1 leading to the efficient accumulation of viral mRNAs and viral proteins during infection.",2011 Dec 8,"['Huang, Cheng', 'Lokugamage, Kumari G.', 'Rozovics, Janet M.', 'Narayanan, Krishna', 'Semler, Bert L.', 'Makino, Shinji']",PLoS Pathog,,,True
be1d63805272f9d58e200bf0a8b57e8136b30af4,PMC,Identifying Hosts of Families of Viruses: A Machine Learning Approach,http://dx.doi.org/10.1371/journal.pone.0027631,PMC3235098,22174744,CC BY,"Identifying emerging viral pathogens and characterizing their transmission is essential to developing effective public health measures in response to an epidemic. Phylogenetics, though currently the most popular tool used to characterize the likely host of a virus, can be ambiguous when studying species very distant to known species and when there is very little reliable sequence information available in the early stages of the outbreak of disease. Motivated by an existing framework for representing biological sequence information, we learn sparse, tree-structured models, built from decision rules based on subsequences, to predict viral hosts from protein sequence data using popular discriminative machine learning tools. Furthermore, the predictive motifs robustly selected by the learning algorithm are found to show strong host-specificity and occur in highly conserved regions of the viral proteome.",2011 Dec 9,"['Raj, Anil', 'Dewar, Michael', 'Palacios, Gustavo', 'Rabadan, Raul', 'Wiggins, Christopher H.']",PLoS One,,,True
1ff54c023f5b659d36e7f00e9b853e548e3f2875,PMC,Identifying Hosts of Families of Viruses: A Machine Learning Approach,http://dx.doi.org/10.1371/journal.pone.0027631,PMC3235098,22174744,CC BY,"Identifying emerging viral pathogens and characterizing their transmission is essential to developing effective public health measures in response to an epidemic. Phylogenetics, though currently the most popular tool used to characterize the likely host of a virus, can be ambiguous when studying species very distant to known species and when there is very little reliable sequence information available in the early stages of the outbreak of disease. Motivated by an existing framework for representing biological sequence information, we learn sparse, tree-structured models, built from decision rules based on subsequences, to predict viral hosts from protein sequence data using popular discriminative machine learning tools. Furthermore, the predictive motifs robustly selected by the learning algorithm are found to show strong host-specificity and occur in highly conserved regions of the viral proteome.",2011 Dec 9,"['Raj, Anil', 'Dewar, Michael', 'Palacios, Gustavo', 'Rabadan, Raul', 'Wiggins, Christopher H.']",PLoS One,,,False
295415768cd300ee4e31ab6d8988ed15b0b25815,PMC,Identifying Hosts of Families of Viruses: A Machine Learning Approach,http://dx.doi.org/10.1371/journal.pone.0027631,PMC3235098,22174744,CC BY,"Identifying emerging viral pathogens and characterizing their transmission is essential to developing effective public health measures in response to an epidemic. Phylogenetics, though currently the most popular tool used to characterize the likely host of a virus, can be ambiguous when studying species very distant to known species and when there is very little reliable sequence information available in the early stages of the outbreak of disease. Motivated by an existing framework for representing biological sequence information, we learn sparse, tree-structured models, built from decision rules based on subsequences, to predict viral hosts from protein sequence data using popular discriminative machine learning tools. Furthermore, the predictive motifs robustly selected by the learning algorithm are found to show strong host-specificity and occur in highly conserved regions of the viral proteome.",2011 Dec 9,"['Raj, Anil', 'Dewar, Michael', 'Palacios, Gustavo', 'Rabadan, Raul', 'Wiggins, Christopher H.']",PLoS One,,,False
35593b9b140bf1c91c758584ed4e924dd7798436,PMC,Cochrane Systematic Reviews of Chinese Herbal Medicines: An Overview,http://dx.doi.org/10.1371/journal.pone.0028696,PMC3235143,22174870,CC BY,"OBJECTIVES: Our study had two objectives: a) to systematically identify all existing systematic reviews of Chinese herbal medicines (CHM) published in Cochrane Library; b) to assess the methodological quality of included reviews. METHODOLOGY/PRINCIPAL FINDINGS: We performed a systematic search of the Cochrane Database of Systematic Reviews (CDSR, Issue 5, 2010) to identify all reviews of CHM. A total of fifty-eight reviews were eligible for our study. Twenty-one of the included reviews had at least one Traditional Chinese Medicine (TCM) practitioner as its co-author. 7 reviews didn't include any primary study, the remaining reviews (n = 51) included a median of 9 studies and 936 participants. 50% of reviews were last assessed as up-to-date prior to 2008. The questions addressed by 39 reviews were broad in scope, in which 9 reviews combined studies with different herbal medicines. For OQAQ, the mean of overall quality score (item 10) was 5.05 (95% CI; 4.58-5.52). All reviews assessed the methodological quality of primary studies, 16% of included primary studies used adequate sequence generation and 7% used adequate allocation concealment. Of the 51 nonempty reviews, 23 reviews were reported as being inconclusive, while 27 concluded that there might be benefit of CHM, which was limited by the poor quality or inadequate quantity of included studies. 58 reviews reported searching a median of seven electronic databases, while 10 reviews did not search any Chinese database. CONCLUSIONS: Now CDSR has included large numbers of CHM reviews, our study identified some areas which could be improved, such as almost half of included reviews did not have the participation of TCM practitioners and were not up-to-date according to Cochrane criteria, some reviews pooled the results of different herbal medicines and ignored the searching of Chinese databases.",2011 Dec 9,"['Hu, Jing', 'Zhang, Junhua', 'Zhao, Wei', 'Zhang, Yongling', 'Zhang, Li', 'Shang, Hongcai']",PLoS One,,,True
3941bfed937029a31746847f195aeb98631f8d0d,PMC,Function of Membrane Rafts in Viral Lifecycles and Host Cellular Response,http://dx.doi.org/10.1155/2011/245090,PMC3235436,22191032,CC BY,"Membrane rafts are small (10–200 nm) sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. Membrane rafts play an important role in viral infection cycles and viral virulence. Viruses are divided into four main classes, enveloped DNA virus, enveloped RNA virus, nonenveloped DNA virus, and nonenveloped RNA virus. General virus infection cycle is also classified into two sections, the early stage (entry process) and the late stage (assembly, budding, and release processes of virus particles). In the viral cycle, membrane rafts act as a scaffold of many cellular signal transductions, which are associated with symptoms caused by viral infections. In this paper, we describe the functions of membrane rafts in viral lifecycles and host cellular response according to each virus classification, each stage of the virus lifecycle, and each virus-induced signal transduction.",2011 Dec 7,"['Takahashi, Tadanobu', 'Suzuki, Takashi']",Biochem Res Int,,,True
8856e1f2644acc2d51c57d3ead6dd14a929a014b,PMC,Interferon Lambda: A New Sword in Cancer Immunotherapy,http://dx.doi.org/10.1155/2011/349575,PMC3235441,22190970,CC BY,"The discovery of the interferon-lambda (IFN-λ) family has considerably contributed to our understanding of the role of interferon not only in viral infections but also in cancer. IFN-λ proteins belong to the new type III IFN group. Type III IFN is structurally similar to type II IFN (IFN-γ) but functionally identical to type I IFN (IFN-α/β). However, in contrast to type I or type II IFNs, the response to type III IFN is highly cell-type specific. Only epithelial-like cells and to a lesser extent some immune cells respond to IFN-λ. This particular pattern of response is controlled by the differential expression of the IFN-λ receptor, which, in contrast to IFN-α, should result in limited side effects in patients. Recently, we and other groups have shown in several animal models a potent antitumor role of IFN-λ that will open a new challenging era for the current IFN therapy.",2011 Dec 6,"['Lasfar, Ahmed', 'Abushahba, Walid', 'Balan, Murugabaskar', 'Cohen-Solal, Karine A.']",Clin Dev Immunol,,,True
12bc88e7428c240181f181ca0358dac85ae16289,PMC,Current Status of the Immunomodulation and Immunomediated Therapeutic Strategies for Multiple Sclerosis,http://dx.doi.org/10.1155/2012/970789,PMC3235500,22203863,CC BY,"Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and CD4(+) T cells form the core immunopathogenic cascade leading to chronic inflammation. Traditionally, Th1 cells (interferon-γ-producing CD4(+) T cells) driven by interleukin 12 (IL12) were considered to be the encephalitogenic T cells in MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Currently, Th17 cells (Il17-producing CD4(+) T cells) are considered to play a fundamental role in the immunopathogenesis of EAE. This paper highlights the growing evidence that Th17 cells play the core role in the complex adaptive immunity of EAE/MS and discusses the roles of the associated immune cells and cytokines. These constitute the modern immunological basis for the development of novel clinical and preclinical immunomodulatory therapies for MS discussed in this paper.",2012 Dec 6,"['Chen, Shyi-Jou', 'Wang, Yen-Ling', 'Fan, Hueng-Chuen', 'Lo, Wen-Tsung', 'Wang, Chih-Chien', 'Sytwu, Huey-Kang']",Clin Dev Immunol,,,True
b56324b4de371913188d3eae4437eaaeda3b814b,PMC,Long-Term Prediction of Emergency Department Revenue and Visitor Volume Using Autoregressive Integrated Moving Average Model,http://dx.doi.org/10.1155/2011/395690,PMC3235663,22203886,CC BY,"This study analyzed meteorological, clinical and economic factors in terms of their effects on monthly ED revenue and visitor volume. Monthly data from January 1, 2005 to September 30, 2009 were analyzed. Spearman correlation and cross-correlation analyses were performed to identify the correlation between each independent variable, ED revenue, and visitor volume. Autoregressive integrated moving average (ARIMA) model was used to quantify the relationship between each independent variable, ED revenue, and visitor volume. The accuracies were evaluated by comparing model forecasts to actual values with mean absolute percentage of error. Sensitivity of prediction errors to model training time was also evaluated. The ARIMA models indicated that mean maximum temperature, relative humidity, rainfall, non-trauma, and trauma visits may correlate positively with ED revenue, but mean minimum temperature may correlate negatively with ED revenue. Moreover, mean minimum temperature and stock market index fluctuation may correlate positively with trauma visitor volume. Mean maximum temperature, relative humidity and stock market index fluctuation may correlate positively with non-trauma visitor volume. Mean maximum temperature and relative humidity may correlate positively with pediatric visitor volume, but mean minimum temperature may correlate negatively with pediatric visitor volume. The model also performed well in forecasting revenue and visitor volume.",2011 Dec 4,"['Chen, Chieh-Fan', 'Ho, Wen-Hsien', 'Chou, Huei-Yin', 'Yang, Shu-Mei', 'Chen, I-Te', 'Shi, Hon-Yi']",Comput Math Methods Med,,,True
c405097039f3cfefa4c6cf436925d3e3c8c3e013,PMC,"Culling-Induced Changes in Badger (Meles meles) Behaviour, Social Organisation and the Epidemiology of Bovine Tuberculosis",http://dx.doi.org/10.1371/journal.pone.0028904,PMC3237560,22194946,CC BY,"In the UK, attempts since the 1970s to control the incidence of bovine tuberculosis (bTB) in cattle by culling a wildlife host, the European badger (Meles meles), have produced equivocal results. Culling-induced social perturbation of badger populations may lead to unexpected outcomes. We test predictions from the ‘perturbation hypothesis’, determining the impact of culling operations on badger populations, movement of surviving individuals and the influence on the epidemiology of bTB in badgers using data dervied from two study areas within the UK Government's Randomised Badger Culling Trial (RBCT). Culling operations did not remove all individuals from setts, with between 34–43% of badgers removed from targeted social groups. After culling, bTB prevalence increased in badger social groups neighbouring removals, particularly amongst cubs. Seventy individual adult badgers were fitted with radio-collars, yielding 8,311 locational fixes from both sites between November 2001 and December 2003. Home range areas of animals surviving within removed groups increased by 43.5% in response to culling. Overlap between summer ranges of individuals from Neighbouring social groups in the treatment population increased by 73.3% in response to culling. The movement rate of individuals between social groups was low, but increased after culling, in Removed and Neighbouring social groups. Increased bTB prevalence in Neighbouring groups was associated with badger movements both into and out of these groups, although none of the moving individuals themselves tested positive for bTB. Significant increases in both the frequency of individual badger movements between groups and the emergence of bTB were observed in response to culling. However, no direct evidence was found to link the two phenomena. We hypothesise that the social disruption caused by culling may not only increase direct contact and thus disease transmission between surviving badgers, but may also increase social stress within the surviving population, causing immunosuppression and enhancing the expression of disease.",2011 Dec 14,"['Riordan, Philip', 'Delahay, Richard John', 'Cheeseman, Chris', 'Johnson, Paul James', 'Macdonald, David Whyte']",PLoS One,,,True
2b5319418280dbd7a7f5348c57c2a43b1fabc150,PMC,Adoption of an infection prevention and control programme (IPCP) in the Republic of Kiribati: a case study in diffusion of innovations theory,http://dx.doi.org/10.1186/1753-6561-5-S6-O20,PMC3239431,,CC BY,,2011 Jun 29,"['Zimmerman, P-A', 'Yeatman, H', 'Jones, M', 'Murdoch, H']",BMC Proc,,,False
740a8ab7bf183f64284384c5dfaae0ae77d56558,PMC,Synergistic Roles of Eukaryotic Translation Elongation Factors 1Bγ and 1A in Stimulation of Tombusvirus Minus-Strand Synthesis,http://dx.doi.org/10.1371/journal.ppat.1002438,PMC3240602,22194687,CC BY,"Host factors are recruited into viral replicase complexes to aid replication of plus-strand RNA viruses. In this paper, we show that deletion of eukaryotic translation elongation factor 1Bgamma (eEF1Bγ) reduces Tomato bushy stunt virus (TBSV) replication in yeast host. Also, knock down of eEF1Bγ level in plant host decreases TBSV accumulation. eEF1Bγ binds to the viral RNA and is one of the resident host proteins in the tombusvirus replicase complex. Additional in vitro assays with whole cell extracts prepared from yeast strains lacking eEF1Bγ demonstrated its role in minus-strand synthesis by opening of the structured 3′ end of the viral RNA and reducing the possibility of re-utilization of (+)-strand templates for repeated (-)-strand synthesis within the replicase. We also show that eEF1Bγ plays a synergistic role with eukaryotic translation elongation factor 1A in tombusvirus replication, possibly via stimulation of the proper positioning of the viral RNA-dependent RNA polymerase over the promoter region in the viral RNA template.These roles for translation factors during TBSV replication are separate from their canonical roles in host and viral protein translation.",2011 Dec 15,"['Sasvari, Zsuzsanna', 'Izotova, Lara', 'Kinzy, Terri Goss', 'Nagy, Peter D.']",PLoS Pathog,,,True
d11eb07952f5a0fb076a49935508707abeecf8af,PMC,Clinical and Functional Characterization of URAT1 Variants,http://dx.doi.org/10.1371/journal.pone.0028641,PMC3241677,22194875,CC BY,"Idiopathic renal hypouricaemia is an inherited form of hypouricaemia, associated with abnormal renal handling of uric acid. There is excessive urinary wasting of uric acid resulting in hypouricaemia. Patients may be asymptomatic, but the persistent urinary abnormalities may manifest as renal stone disease, and hypouricaemia may manifest as exercise induced acute kidney injury. Here we have identified Macedonian and British patients with hypouricaemia, who presented with a variety of renal symptoms and signs including renal stone disease, hematuria, pyelonephritis and nephrocalcinosis. We have identified heterozygous missense mutations in SLC22A12 encoding the urate transporter protein URAT1 and correlate these genetic findings with functional characterization. Urate handling was determined using uptake experiments in HEK293 cells. This data highlights the importance of the URAT1 renal urate transporter in determining serum urate concentrations and the clinical phenotypes, including nephrolithiasis, that should prompt the clinician to suspect an inherited form of renal hypouricaemia.",2011 Dec 16,"['Tasic, Velibor', 'Hynes, Ann Marie', 'Kitamura, Kenichiro', 'Cheong, Hae Il', 'Lozanovski, Vladimir J.', 'Gucev, Zoran', 'Jutabha, Promsuk', 'Anzai, Naohiko', 'Sayer, John A.']",PLoS One,,,True
78f10dd6eb8860062bac9d5261b6881768bd7d7b,PMC,Internal versus external determinants of Schistosoma japonicum transmission in irrigated agricultural villages,http://dx.doi.org/10.1098/rsif.2011.0285,PMC3243390,21752808,CC BY,"Currently schistosomiasis transmission has been suppressed to low levels in many historically endemic areas of China by widespread use of praziquantel in human and bovine populations and application of niclosamide for snail control. However, re-emergent transmission has signalled the need for sustainable interventions beyond these repeated chemical interventions. To take advantage of ongoing investment in rural infrastructure, an index of schistosomiasis transmission potential is needed to identify villages where environmental modifications would be particularly effective. Based on a retrospective analysis of data from 10 villages in Sichuan Province, an index linked to the basic reproductive number is shown to have promise in meeting this need. However, a lack of methods for estimating the spatial components of the proposed metric and for estimating the import of cercariae and miracidia from neighbouring villages leads to significant uncertainty in its estimation. These findings suggest a priority effort to develop methods for measuring the free-swimming forms of the parasite in surface waters. This need is underscored by the high cost and limited sensitivity of current methods for diagnosing human infection and mounting evidence of the inadequacy of snail surveys to identify environments supporting low levels of transmission.",2012 Feb 7,"Spear, Robert C.",J R Soc Interface,,,True
ba03011c4b23d19642ea33554a6789895558ad97,PMC,Polyvalent DNA Vaccines Expressing HA Antigens of H5N1 Influenza Viruses with an Optimized Leader Sequence Elicit Cross-Protective Antibody Responses,http://dx.doi.org/10.1371/journal.pone.0028757,PMC3244406,22205966,CC BY,"Highly pathogenic avian influenza A (HPAI) H5N1 viruses are circulating among poultry populations in parts of Asia, Africa, and the Middle East, and have caused human infections with a high mortality rate. H5 subtype hemagglutinin (HA) has evolved into phylogenetically distinct clades and subclades based on viruses isolated from various avian species. Since 1997, humans have been infected by HPAI H5N1 viruses from several clades. It is, therefore, important to develop strategies to produce protective antibody responses against H5N1 viruses from multiple clades or antigenic groups. In the current study, we optimized the signal peptide design of DNA vaccines expressing HA antigens from H5N1 viruses. Cross reactivity analysis using sera from immunized rabbits showed that antibody responses elicited by a polyvalent formulation, including HA antigens from different clades, was able to elicit broad protective antibody responses against multiple key representative H5N1 viruses across different clades. Data presented in this report support the development of a polyvalent DNA vaccine strategy against the threat of a potential H5N1 influenza pandemic.",2011 Dec 21,"['Wang, Shixia', 'Hackett, Anthony', 'Jia, Na', 'Zhang, Chunhua', 'Zhang, Lu', 'Parker, Chris', 'Zhou, An', 'Li, Jun', 'Cao, Wu-Chun', 'Huang, Zuhu', 'Li, Yan', 'Lu, Shan']",PLoS One,,,True
716bf47d34e36f3c165ee3c84a70d93bf6f0bf5d,PMC,Epithelial Cells Derived from Swine Bone Marrow Express Stem Cell Markers and Support Influenza Virus Replication In Vitro,http://dx.doi.org/10.1371/journal.pone.0029567,PMC3245290,22216319,CC BY,"The bone marrow contains heterogeneous population of cells that are involved in the regeneration and repair of diseased organs, including the lungs. In this study, we isolated and characterized progenitor epithelial cells from the bone marrow of 4- to 5-week old germ-free pigs. Microscopically, the cultured cells showed epithelial-like morphology. Phenotypically, these cells expressed the stem cell markers octamer-binding transcription factor (Oct4) and stage-specific embryonic antigen-1 (SSEA-1), the alveolar stem cell marker Clara cell secretory protein (Ccsp), and the epithelial cell markers pan-cytokeratin (Pan-K), cytokeratin-18 (K-18), and occludin. When cultured in epithelial cell growth medium, the progenitor epithelial cells expressed type I and type II pneumocyte markers. Next, we examined the susceptibility of these cells to influenza virus. Progenitor epithelial cells expressed sialic acid receptors utilized by avian and mammalian influenza viruses and were targets for influenza virus replication. Additionally, differentiated type II but not type I pneumocytes supported the replication of influenza virus. Our data indicate that we have identified a unique population of progenitor epithelial cells in the bone marrow that might have airway reconstitution potential and may be a useful model for cell-based therapies for infectious and non-infectious lung diseases.",2011 Dec 22,"['Khatri, Mahesh', 'Saif, Yehia M.']",PLoS One,,,True
62426ec5038825e2c7928b6ac82a66ff1c2a578e,PMC,Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine,http://dx.doi.org/10.1371/journal.pcbi.1002315,PMC3245300,22215997,CC BY,"The H1N1 influenza pandemic of 2009 has claimed over 18,000 lives. During this pandemic, development of drug resistance further complicated efforts to control and treat the widespread illness. This research utilizes traditional Chinese medicine Database@Taiwan (TCM Database@Taiwan) to screen for compounds that simultaneously target H1 and N1 to overcome current difficulties with virus mutations. The top three candidates were de novo derivatives of xylopine and rosmaricine. Bioactivity of the de novo derivatives against N1 were validated by multiple machine learning prediction models. Ability of the de novo compounds to maintain CoMFA/CoMSIA contour and form key interactions implied bioactivity within H1 as well. Addition of a pyridinium fragment was critical to form stable interactions in H1 and N1 as supported by molecular dynamics (MD) simulation. Results from MD, hydrophobic interactions, and torsion angles are consistent and support the findings of docking. Multiple anchors and lack of binding to residues prone to mutation suggest that the TCM de novo derivatives may be resistant to drug resistance and are advantageous over conventional H1N1 treatments such as oseltamivir. These results suggest that the TCM de novo derivatives may be suitable candidates of dual-targeting drugs for influenza.",2011 Dec 22,"['Chang, Su-Sen', 'Huang, Hung-Jin', 'Chen, Calvin Yu-Chian']",PLoS Comput Biol,,,True
1f33cc82e136a1cc89b2382e6fcc6ae520e364ab,PMC,"Genetic diversity of group A rotaviruses associated with repeated outbreaks of diarrhea in a farrow-to-finish farm: identification of a porcine rotavirus strain bearing a novel VP7 genotype, G26",http://dx.doi.org/10.1186/1297-9716-42-112,PMC3245447,22067072,CC BY,"Group A rotaviruses (GARs) are one of the most common causes of diarrhea in suckling pigs. Although a number of G and P genotypes have been identified in porcine GARs, few attempts have been made to study the molecular epidemiology of these viruses associated with diarrhea outbreaks within a farm over an extended period of time. Here, we investigated the molecular characteristics of GARs that caused four outbreaks of diarrhea among suckling pigs in a farrow-to-finish farm over the course of a year. G and P genotyping of GARs detected at each outbreak demonstrated genetic diversity in this farm as follows: G9P[23] was detected at the first outbreak, G9P[13]/[22] and G9P[23] at the second, G3P[7] at the third, and G9P[23], G5P[13]/[22], and P[7] combined with an untypeable G genotype at the fourth. Sequence analysis of the detected GARs revealed that such genetic diversity could have resulted not only from the introduction of new GAR strains, but also from gene reassortment between GAR strains within the farm. Further, the GAR strain carrying the untypeable G genotype was shown to be a novel porcine GAR bearing a new G26 genotype, as confirmed by the Rotavirus Classification Working Group.",2011 Nov 9,"['Miyazaki, Ayako', 'Kuga, Kazufumi', 'Suzuki, Tohru', 'Kohmoto, Mariko', 'Katsuda, Ken', 'Tsunemitsu, Hiroshi']",Vet Res,,,True
026c59766e222f22b416a6525ae3194a140b5faa,PMC,Two Novel Parvoviruses in Frugivorous New and Old World Bats,http://dx.doi.org/10.1371/journal.pone.0029140,PMC3246463,22216187,CC BY,"Bats, a globally distributed group of mammals with high ecological importance, are increasingly recognized as natural reservoir hosts for viral agents of significance to human and animal health. In the present study, we evaluated pools of blood samples obtained from two phylogenetically distant bat families, in particular from flying foxes (Pteropodidae), Eidolon helvum in West Africa, and from two species of New World leaf-nosed fruit bats (Phyllostomidae), Artibeus jamaicensis and Artibeus lituratus in Central America. A sequence-independent virus discovery technique (VIDISCA) was used in combination with high throughput sequencing to detect two novel parvoviruses: a PARV4-like virus named Eh-BtPV-1 in Eidolon helvum from Ghana and the first member of a putative new genus in Artibeus jamaicensis from Panama (Aj-BtPV-1). Those viruses were circulating in the corresponding bat colony at rates of 7–8%. Aj-BtPV-1 was also found in Artibeus lituratus (5.5%). Both viruses were detected in the blood of infected animals at high concentrations: up to 10E8 and to 10E10 copies/ml for Aj-BtPV-1 and Eh-BtPV-1 respectively. Eh-BtPV-1 was additionally detected in all organs collected from bats (brain, lungs, liver, spleen, kidneys and intestine) and spleen and kidneys were identified as the most likely sites where viral replication takes place. Our study shows that bat parvoviruses share common ancestors with known parvoviruses of humans and livestock. We also provide evidence that a variety of Parvovirinae are able to cause active infection in bats and that they are widely distributed in these animals with different geographic origin, ecologies and climatic ranges.",2011 Dec 27,"['Canuti, Marta', 'Eis-Huebinger, Anna Maria', 'Deijs, Martin', 'de Vries, Michel', 'Drexler, Jan Felix', 'Oppong, Samuel K.', 'Müller, Marcel A.', 'Klose, Stefan M.', 'Wellinghausen, Nele', 'Cottontail, Veronika M.', 'Kalko, Elisabeth K. V.', 'Drosten, Christian', 'van der Hoek, Lia']",PLoS One,,,True
550494d6d01569a05a8ca2d75f892486b01d1865,PMC,Diseases and Causes of Death in European Bats: Dynamics in Disease Susceptibility and Infection Rates,http://dx.doi.org/10.1371/journal.pone.0029773,PMC3247292,22216354,CC BY,"BACKGROUND: Bats receive increasing attention in infectious disease studies, because of their well recognized status as reservoir species for various infectious agents. This is even more important, as bats with their capability of long distance dispersal and complex social structures are unique in the way microbes could be spread by these mammalian species. Nevertheless, infection studies in bats are predominantly limited to the identification of specific pathogens presenting a potential health threat to humans. But the impact of infectious agents on the individual host and their importance on bat mortality is largely unknown and has been neglected in most studies published to date. METHODOLOGY/PRINCIPAL FINDINGS: Between 2002 and 2009, 486 deceased bats of 19 European species (family Vespertilionidae) were collected in different geographic regions in Germany. Most animals represented individual cases that have been incidentally found close to roosting sites or near human habitation in urban and urban-like environments. The bat carcasses were subjected to a post-mortem examination and investigated histo-pathologically, bacteriologically and virologically. Trauma and disease represented the most important causes of death in these bats. Comparative analysis of pathological findings and microbiological results show that microbial agents indeed have an impact on bats succumbing to infectious diseases, with fatal bacterial, viral and parasitic infections found in at least 12% of the bats investigated. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the importance of diseases and infectious agents as cause of death in European bat species. The clear seasonal and individual variations in disease prevalence and infection rates indicate that maternity colonies are more susceptible to infectious agents, underlining the possible important role of host physiology, immunity and roosting behavior as risk factors for infection of bats.",2011 Dec 28,"['Mühldorfer, Kristin', 'Speck, Stephanie', 'Kurth, Andreas', 'Lesnik, René', 'Freuling, Conrad', 'Müller, Thomas', 'Kramer-Schadt, Stephanie', 'Wibbelt, Gudrun']",PLoS One,,,True
aefd921eef67855fd84f460502e9e7277aeb92a1,PMC,Collaboration between infection control and occupational health in three continents: a success story with international impact,http://dx.doi.org/10.1186/1472-698X-11-S2-S8,PMC3247839,22166059,CC BY,"Globalization has been accompanied by the rapid spread of infectious diseases, and further strain on working conditions for health workers globally. Post-SARS, Canadian occupational health and infection control researchers got together to study how to better protect health workers, and found that training was indeed perceived as key to a positive safety culture. This led to developing information and communication technology (ICT) tools. The research conducted also showed the need for better workplace inspections, so a workplace audit tool was also developed to supplement worker questionnaires and the ICT. When invited to join Ecuadorean colleagues to promote occupational health and infection control, these tools were collectively adapted and improved, including face-to-face as well as on-line problem-based learning scenarios. The South African government then invited the team to work with local colleagues to improve occupational health and infection control, resulting in an improved web-based health information system to track incidents, exposures, and occupational injury and diseases. As the H1N1 pandemic struck, the online infection control course was adapted and translated into Spanish, as was a novel skill-building learning tool that permits health workers to practice selecting personal protective equipment. This tool was originally developed in collaboration with the countries from the Caribbean region and the Pan American Health Organization (PAHO). Research from these experiences led to strengthened focus on building capacity of health and safety committees, and new modules are thus being created, informed by that work. The products developed have been widely heralded as innovative and interactive, leading to their inclusion into “toolkits” used internationally. The tools used in Canada were substantially improved from the collaborative adaptation process for South and Central America and South Africa. This international collaboration between occupational health and infection control researchers led to the improvement of the research framework and development of tools, guidelines and information systems. Furthermore, the research and knowledge-transfer experience highlighted the value of partnership amongst Northern and Southern researchers in terms of sharing resources, experiences and knowledge.",2011 Nov 8,"['Yassi, Annalee', 'Bryce, Elizabeth A', 'Breilh, Jaime', 'Lavoie, Marie-Claude', 'Ndelu, Lindiwe', 'Lockhart, Karen', 'Spiegel, Jerry']",BMC Int Health Hum Rights,,,True
e344d21fb68d14bed65d7fbdc97164e61717a0f2,PMC,Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions,http://dx.doi.org/10.1371/journal.pone.0029491,PMC3248422,22220213,CC BY,"Given a compound, how can we effectively predict its biological function? It is a fundamentally important problem because the information thus obtained may benefit the understanding of many basic biological processes and provide useful clues for drug design. In this study, based on the information of chemical-chemical interactions, a novel method was developed that can be used to identify which of the following eleven metabolic pathway classes a query compound may be involved with: (1) Carbohydrate Metabolism, (2) Energy Metabolism, (3) Lipid Metabolism, (4) Nucleotide Metabolism, (5) Amino Acid Metabolism, (6) Metabolism of Other Amino Acids, (7) Glycan Biosynthesis and Metabolism, (8) Metabolism of Cofactors and Vitamins, (9) Metabolism of Terpenoids and Polyketides, (10) Biosynthesis of Other Secondary Metabolites, (11) Xenobiotics Biodegradation and Metabolism. It was observed that the overall success rate obtained by the method via the 5-fold cross-validation test on a benchmark dataset consisting of 3,137 compounds was 77.97%, which is much higher than 10.45%, the corresponding success rate obtained by the random guesses. Besides, to deal with the situation that some compounds may be involved with more than one metabolic pathway class, the method presented here is featured by the capacity able to provide a series of potential metabolic pathway classes ranked according to the descending order of their likelihood for each of the query compounds concerned. Furthermore, our method was also applied to predict 5,549 compounds whose metabolic pathway classes are unknown. Interestingly, the results thus obtained are quite consistent with the deductions from the reports by other investigators. It is anticipated that, with the continuous increase of the chemical-chemical interaction data, the current method will be further enhanced in its power and accuracy, so as to become a useful complementary vehicle in annotating uncharacterized compounds for their biological functions.",2011 Dec 29,"['Hu, Le-Le', 'Chen, Chen', 'Huang, Tao', 'Cai, Yu-Dong', 'Chou, Kuo-Chen']",PLoS One,,,True
5b6ffa9ab26b453363555a8ab5943464a9f0c5e5,PMC,Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions,http://dx.doi.org/10.1371/journal.pone.0029491,PMC3248422,22220213,CC BY,"Given a compound, how can we effectively predict its biological function? It is a fundamentally important problem because the information thus obtained may benefit the understanding of many basic biological processes and provide useful clues for drug design. In this study, based on the information of chemical-chemical interactions, a novel method was developed that can be used to identify which of the following eleven metabolic pathway classes a query compound may be involved with: (1) Carbohydrate Metabolism, (2) Energy Metabolism, (3) Lipid Metabolism, (4) Nucleotide Metabolism, (5) Amino Acid Metabolism, (6) Metabolism of Other Amino Acids, (7) Glycan Biosynthesis and Metabolism, (8) Metabolism of Cofactors and Vitamins, (9) Metabolism of Terpenoids and Polyketides, (10) Biosynthesis of Other Secondary Metabolites, (11) Xenobiotics Biodegradation and Metabolism. It was observed that the overall success rate obtained by the method via the 5-fold cross-validation test on a benchmark dataset consisting of 3,137 compounds was 77.97%, which is much higher than 10.45%, the corresponding success rate obtained by the random guesses. Besides, to deal with the situation that some compounds may be involved with more than one metabolic pathway class, the method presented here is featured by the capacity able to provide a series of potential metabolic pathway classes ranked according to the descending order of their likelihood for each of the query compounds concerned. Furthermore, our method was also applied to predict 5,549 compounds whose metabolic pathway classes are unknown. Interestingly, the results thus obtained are quite consistent with the deductions from the reports by other investigators. It is anticipated that, with the continuous increase of the chemical-chemical interaction data, the current method will be further enhanced in its power and accuracy, so as to become a useful complementary vehicle in annotating uncharacterized compounds for their biological functions.",2011 Dec 29,"['Hu, Le-Le', 'Chen, Chen', 'Huang, Tao', 'Cai, Yu-Dong', 'Chou, Kuo-Chen']",PLoS One,,,False
fc9a6a00498ee4dfeaf7c201c3341aca6ad21409,PMC,Identification and Characterization of a Novel Non-Structural Protein of Bluetongue Virus,http://dx.doi.org/10.1371/journal.ppat.1002477,PMC3248566,22241985,CC BY,"Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell.",2011 Dec 29,"['Ratinier, Maxime', 'Caporale, Marco', 'Golder, Matthew', 'Franzoni, Giulia', 'Allan, Kathryn', 'Nunes, Sandro Filipe', 'Armezzani, Alessia', 'Bayoumy, Amr', 'Rixon, Frazer', 'Shaw, Andrew', 'Palmarini, Massimo']",PLoS Pathog,,,True
ea77ef3c24536b33485875684a34ca6539084c5c,PMC,Acute Respiratory Distress Syndrome Induced by a Swine 2009 H1N1 Variant in Mice,http://dx.doi.org/10.1371/journal.pone.0029347,PMC3250439,22235288,CC BY,"BACKGROUND: Acute respiratory distress syndrome (ARDS) induced by pandemic 2009 H1N1 influenza virus has been widely reported and was considered the main cause of death in critically ill patients with 2009 H1N1 infection. However, no animal model has been developed for ARDS caused by infection with 2009 H1N1 virus. Here, we present a mouse model of ARDS induced by 2009 H1N1 virus. METHODOLOGY PRINCIPAL FINDINGS: Mice were inoculated with A/swine/Shandong/731/2009 (SD/09), which was a 2009 H1N1 influenza variant with a G222D mutation in the hemagglutinin. Clinical symptoms were recorded every day. Lung injury was assessed by lung water content and histopathological observation. Arterial blood gas, leukocyte count in the bronchial alveolar lavage fluid and blood, virus titers, and cytokine levels in the lung were measured at various times post-inoculation. Mice infected with SD/09 virus showed typical ARDS symptoms characterized by 60% lethality on days 8–10 post-inoculation, highly edematous lungs, inflammatory cellular infiltration, alveolar and interstitial edema, lung hemorrhage, progressive and severe hypoxemia, and elevated levels of proinflammatory cytokines and chemokines. CONCLUSIONS/SIGNIFICANCE: These results suggested that we successfully established an ARDS mouse model induced by a virulent 2009 H1N1 variant without previous adaptation, which may be of benefit for evaluating the pathogenesis or therapy of human ARDS caused by 2009 H1N1 virus.",2012 Jan 3,"['Zhang, Yi', 'Sun, Honglei', 'Fan, Lihong', 'Ma, Yuan', 'Sun, Yipeng', 'Pu, Juan', 'Yang, Jun', 'Qiao, Jian', 'Ma, Guangpeng', 'Liu, Jinhua']",PLoS One,,,True
315303952d93ba93f55029cca73e2f483bc16362,PMC,True versus False Parasite Interactions: A Robust Method to Take Risk Factors into Account and Its Application to Feline Viruses,http://dx.doi.org/10.1371/journal.pone.0029618,PMC3250451,22235312,CC BY,"BACKGROUND: Multiple infections are common in natural host populations and interspecific parasite interactions are therefore likely within a host individual. As they may seriously impact the circulation of certain parasites and the emergence and management of infectious diseases, their study is essential. In the field, detecting parasite interactions is rendered difficult by the fact that a large number of co-infected individuals may also be observed when two parasites share common risk factors. To correct for these “false interactions”, methods accounting for parasite risk factors must be used. METHODOLOGY/PRINCIPAL FINDINGS: In the present paper we propose such a method for presence-absence data (i.e., serology). Our method enables the calculation of the expected frequencies of single and double infected individuals under the independence hypothesis, before comparing them to the observed ones using the chi-square statistic. The method is termed “the corrected chi-square.” Its robustness was compared to a pre-existing method based on logistic regression and the corrected chi-square proved to be much more robust for small sample sizes. Since the logistic regression approach is easier to implement, we propose as a rule of thumb to use the latter when the ratio between the sample size and the number of parameters is above ten. Applied to serological data for four viruses infecting cats, the approach revealed pairwise interactions between the Feline Herpesvirus, Parvovirus and Calicivirus, whereas the infection by FIV, the feline equivalent of HIV, did not modify the risk of infection by any of these viruses. CONCLUSIONS/SIGNIFICANCE: This work therefore points out possible interactions that can be further investigated in experimental conditions and, by providing a user-friendly R program and a tutorial example, offers new opportunities for animal and human epidemiologists to detect interactions of interest in the field, a crucial step in the challenge of multiple infections.",2012 Jan 3,"['Hellard, Eléonore', 'Pontier, Dominique', 'Sauvage, Frank', 'Poulet, Hervé', 'Fouchet, David']",PLoS One,,,True
2239f23b3b6738f24cd381b0ee59faaf39a8a027,PMC,The Transmembrane Domain of CEACAM1-4S Is a Determinant of Anchorage Independent Growth and Tumorigenicity,http://dx.doi.org/10.1371/journal.pone.0029606,PMC3250453,22235309,CC BY,"CEACAM1 is a multifunctional Ig-like cell adhesion molecule expressed by epithelial cells in many organs. CEACAM1-4L and CEACAM1-4S, two isoforms produced by differential splicing, are predominant in rat liver. Previous work has shown that downregulation of both isoforms occurs in rat hepatocellular carcinomas. Here, we have isolated an anchorage dependent clone, designated 253T-NT that does not express detectable levels of CEACAM1. Stable transfection of 253-NT cells with a wild type CEACAM1-4S expression vector induced an anchorage independent growth in vitro and a tumorigenic phenotype in vivo. These phenotypes were used as quantifiable end points to examine the functionality of the CEACAM1-4S transmembrane domain. Examination of the CEACAM1 transmembrane domain showed N-terminal GXXXG dimerization sequences and C-terminal tyrosine residues shown in related studies to stabilize transmembrane domain helix-helix interactions. To examine the effects of transmembrane domain mutations, 253-NT cells were transfected with transmembrane domain mutants carrying glycine to leucine or tyrosine to valine substitutions. Results showed that mutation of transmembrane tyrosine residues greatly enhanced growth in vitro and in vivo. Mutation of transmembrane dimerization motifs, in contrast, significantly reduced anchorage independent growth and tumorigenicity. 253-NT cells expressing CEACAM1-4S with both glycine to leucine and tyrosine to valine mutations displayed the growth-enhanced phenotype of tyrosine mutants. The dramatic effect of transmembrane domain mutations constitutes strong evidence that the transmembrane domain is an important determinant of CEACAM1-4S functionality and most likely by other proteins with transmembrane domains containing dimerization sequences and/or C-terminal tyrosine residues.",2012 Jan 3,"['Lawson, Erica L.', 'Mills, David R.', 'Brilliant, Kate E.', 'Hixson, Douglas C.']",PLoS One,,,True
cdf3bcf39150a5ef5537651e90d93cbccd097f79,PMC,"Etiology and Clinical Characteristics of Influenza-Like Illness (ILI) in Outpatients in Beijing, June 2010 to May 2011",http://dx.doi.org/10.1371/journal.pone.0028786,PMC3251557,22238581,CC BY,"BACKGROUND: Since May 2009, exposure of the population of Beijing, China to pH1N1 has resulted in an increase in respiratory illnesses. Limited information is available on the etiology and clinical characteristics of the influenza-like illness (ILI) that ensued in adults following the pH1N1 pandemic. METHODS: Clinical and epidemiological data of ILI in adults was collected. A total of 279 throat swabs were tested for twelve respiratory viruses using multiplex RT-PCR. Clinical characteristics of influenza A in outpatients versus test-negative patients were compared using Pearson's χ2 and the Mann-Whitney U test. 190 swabs were tested for pH1N1 by virus isolation. Consultation rates for ILI were compared between 2009 and 2010. RESULTS: One or two virus were detected in 29% of the samples. Influenza A virus (FLU-A) accounted for 22.9% (64/279). Other viruses were present at a frequency less than 3.0%. Cough was significantly associated with Influenza A virus infection (χ2, p<0.001). The positive rate of FLU-A was consistent with changes in the ILI rate during the same period and there was a significant reduction in the incidence of ILI in 2010 when compared to 2009. During the 2010–2011 influenza season, the incidence peaked in January 2011 in Beijing and north China. CONCLUSIONS: Exposure to pH1N1 had no impact on typical influenza seasonal peaks, although FLU-A remained the predominant virus for 2010 in Beijing. Symptomatically, cough was associated with FLU-A infection. The positive rate of influenza virus was consistent with changes in the ILI rate during the same period and there was a significant reduction in the incidence of ILI in 2010 when compared to that of 2009.",2012 Jan 4,"['Yang, XiaoHua', 'Yao, Yao', 'Chen, MeiFang', 'Yang, Xia', 'Xie, YanDi', 'Liu, YaFen', 'Zhao, XiuYing', 'Gao, Yan', 'Wei, Lai']",PLoS One,,,True
a447f42b4f4ed16afea798513f8c1409ee2252fa,PMC,Human Subtilase SKI-1/S1P Is a Master Regulator of the HCV Lifecycle and a Potential Host Cell Target for Developing Indirect-Acting Antiviral Agents,http://dx.doi.org/10.1371/journal.ppat.1002468,PMC3252376,22241994,CC BY,"HCV infection is a major risk factor for liver cancer and liver transplantation worldwide. Overstimulation of host lipid metabolism in the liver by HCV-encoded proteins during viral infection creates a favorable environment for virus propagation and pathogenesis. In this study, we hypothesize that targeting cellular enzymes acting as master regulators of lipid homeostasis could represent a powerful approach to developing a novel class of broad-spectrum antivirals against infection associated with human Flaviviridae viruses such as hepatitis C virus (HCV), whose assembly and pathogenesis depend on interaction with lipid droplets (LDs). One such master regulator of cholesterol metabolic pathways is the host subtilisin/kexin-isozyme-1 (SKI-1) – or site-1 protease (S1P). SKI-1/S1P plays a critical role in the proteolytic activation of sterol regulatory element binding proteins (SREBPs), which control expression of the key enzymes of cholesterol and fatty-acid biosynthesis. Here we report the development of a SKI-1/S1P-specific protein-based inhibitor and its application to blocking the SREBP signaling cascade. We demonstrate that SKI-1/S1P inhibition effectively blocks HCV from establishing infection in hepatoma cells. The inhibitory mechanism is associated with a dramatic reduction in the abundance of neutral lipids, LDs, and the LD marker: adipose differentiation-related protein (ADRP)/perilipin 2. Reduction of LD formation inhibits virus assembly from infected cells. Importantly, we confirm that SKI-1/S1P is a key host factor for HCV infection by using a specific active, site-directed, small-molecule inhibitor of SKI-1/S1P: PF-429242. Our studies identify SKI-1/S1P as both a novel regulator of the HCV lifecycle and as a potential host-directed therapeutic target against HCV infection and liver steatosis. With identification of an increasing number of human viruses that use host LDs for infection, our results suggest that SKI-1/S1P inhibitors may allow development of novel broad-spectrum biopharmaceuticals that could lead to novel indirect-acting antiviral options with the current standard of care.",2012 Jan 5,"['Olmstead, Andrea D.', 'Knecht, Wolfgang', 'Lazarov, Ina', 'Dixit, Surjit B.', 'Jean, François']",PLoS Pathog,,,True
667001630cb051990f577e069785590fce4b4d14,PMC,"Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.",http://dx.doi.org/10.3762/bjoc.7.192,PMC3252867,22238541,CC BY,"The marine-derived fungus Stachylidium sp. was isolated from the sponge Callyspongia sp. cf. C. flammea. Culture on a biomalt medium supplemented with sea salt led to the isolation of three new phthalide derivatives, i.e., marilones A–C (1–3), and the known compound silvaticol (4). The skeleton of marilones A and B is most unusual, and its biosynthesis is suggested to require unique biochemical reactions considering fungal secondary metabolism. Marilone A (1) was found to have antiplasmodial activity against Plasmodium berghei liver stages with an IC(50) of 12.1 µM. Marilone B (2) showed selective antagonistic activity towards the serotonin receptor 5-HT(2B) with a K (i) value of 7.7 µM.",2011 Dec 5,"['Almeida, Celso', 'Kehraus, Stefan', 'Prudêncio, Miguel', 'König, Gabriele M']",Beilstein J Org Chem,,,True
ed50424d38934442bddddf2ce928c4b4d5c2c7d4,PMC,"Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.",http://dx.doi.org/10.3762/bjoc.7.192,PMC3252867,22238541,CC BY,"The marine-derived fungus Stachylidium sp. was isolated from the sponge Callyspongia sp. cf. C. flammea. Culture on a biomalt medium supplemented with sea salt led to the isolation of three new phthalide derivatives, i.e., marilones A–C (1–3), and the known compound silvaticol (4). The skeleton of marilones A and B is most unusual, and its biosynthesis is suggested to require unique biochemical reactions considering fungal secondary metabolism. Marilone A (1) was found to have antiplasmodial activity against Plasmodium berghei liver stages with an IC(50) of 12.1 µM. Marilone B (2) showed selective antagonistic activity towards the serotonin receptor 5-HT(2B) with a K (i) value of 7.7 µM.",2011 Dec 5,"['Almeida, Celso', 'Kehraus, Stefan', 'Prudêncio, Miguel', 'König, Gabriele M']",Beilstein J Org Chem,,,False
5eccf590cffbe86092abe652fa471515e9f37249,PMC,Contact with Domestic Dogs Increases Pathogen Exposure in Endangered African Wild Dogs (Lycaon pictus),http://dx.doi.org/10.1371/journal.pone.0030099,PMC3253127,22238695,CC BY,"BACKGROUND: Infectious diseases have contributed to the decline and local extinction of several wildlife species, including African wild dogs (Lycaon pictus). Mitigating such disease threats is challenging, partly because uncertainty about disease dynamics makes it difficult to identify the best management approaches. Serious impacts on susceptible populations most frequently occur when generalist pathogens are maintained within populations of abundant (often domestic) “reservoir” hosts, and spill over into less abundant host species. If this is the case, disease control directed at the reservoir host might be most appropriate. However, pathogen transmission within threatened host populations may also be important, and may not be controllable by managing another host species. METHODOLOGY/PRINCIPAL FINDINGS: We investigated interspecific and intraspecific transmission routes, by comparing African wild dogs' exposure to six canine pathogens with behavioural measures of their opportunities for contact with domestic dogs and with other wild dogs. Domestic dog contact was associated with exposure to canine parvovirus, Ehrlichia canis, Neospora caninum and perhaps rabies virus, but not with exposure to canine distemper virus or canine coronavirus. Contact with other wild dogs appeared not to increase the risk of exposure to any of the pathogens. CONCLUSIONS/SIGNIFICANCE: These findings, combined with other data, suggest that management directed at domestic dogs might help to protect wild dog populations from rabies virus, but not from canine distemper virus. However, further analyses are needed to determine the management approaches – including no intervention – which are most appropriate for each pathogen.",2012 Jan 6,"['Woodroffe, Rosie', 'Prager, Katherine C.', 'Munson, Linda', 'Conrad, Patricia A.', 'Dubovi, Edward J.', 'Mazet, Jonna A. K.']",PLoS One,,,True
1ba33d95f798c3f591766786b165215875278bc7,PMC,Zoonotic Viruses Associated with Illegally Imported Wildlife Products,http://dx.doi.org/10.1371/journal.pone.0029505,PMC3254615,22253731,CC0,"The global trade in wildlife has historically contributed to the emergence and spread of infectious diseases. The United States is the world's largest importer of wildlife and wildlife products, yet minimal pathogen surveillance has precluded assessment of the health risks posed by this practice. This report details the findings of a pilot project to establish surveillance methodology for zoonotic agents in confiscated wildlife products. Initial findings from samples collected at several international airports identified parts originating from nonhuman primate (NHP) and rodent species, including baboon, chimpanzee, mangabey, guenon, green monkey, cane rat and rat. Pathogen screening identified retroviruses (simian foamy virus) and/or herpesviruses (cytomegalovirus and lymphocryptovirus) in the NHP samples. These results are the first demonstration that illegal bushmeat importation into the United States could act as a conduit for pathogen spread, and suggest that implementation of disease surveillance of the wildlife trade will help facilitate prevention of disease emergence.",2012 Jan 10,"['Smith, Kristine M.', 'Anthony, Simon J.', 'Switzer, William M.', 'Epstein, Jonathan H.', 'Seimon, Tracie', 'Jia, Hongwei', 'Sanchez, Maria D.', 'Huynh, Thanh Thao', 'Galland, G. Gale', 'Shapiro, Sheryl E.', 'Sleeman, Jonathan M.', 'McAloose, Denise', 'Stuchin, Margot', 'Amato, George', 'Kolokotronis, Sergios-Orestis', 'Lipkin, W. Ian', 'Karesh, William B.', 'Daszak, Peter', 'Marano, Nina']",PLoS One,,,True
5eeeb39d1eda252e3ba5fff3596679b8e3376f8d,PMC,"Alzheimer's Disease: APP, Gamma Secretase, APOE, CLU, CR1, PICALM, ABCA7, BIN1, CD2AP, CD33, EPHA1, and MS4A2, and Their Relationships with Herpes Simplex, C. Pneumoniae, Other Suspect Pathogens, and the Immune System",http://dx.doi.org/10.4061/2011/501862,PMC3255168,22254144,CC BY,"Alzheimer's disease susceptibility genes, APP and gamma-secretase, are involved in the herpes simplex life cycle, and that of other suspect pathogens (C. pneumoniae, H. pylori, C. neoformans, B. burgdorferri, P. gingivalis) or immune defence. Such pathogens promote beta-amyloid deposition and tau phosphorylation and may thus be causative agents, whose effects are conditioned by genes. The antimicrobial effects of beta-amyloid, the localisation of APP/gamma-secretase in immunocompetent dendritic cells, and gamma secretase cleavage of numerous pathogen receptors suggest that this network is concerned with pathogen disposal, effects which may be abrogated by the presence of beta-amyloid autoantibodies in the elderly. These autoantibodies, as well as those to nerve growth factor and tau, also observed in Alzheimer's disease, may well be antibodies to pathogens, due to homology between human autoantigens and pathogen proteins. NGF or tau antibodies promote beta-amyloid deposition, neurofibrillary tangles, or cholinergic neuronal loss, and, with other autoantibodies, such as anti-ATPase, are potential agents of destruction, whose formation is dictated by sequence homology between pathogen and human proteins, and thus by pathogen strain and human genes. Pathogen elimination in the ageing population and removal of culpable autoantibodies might reduce the incidence and offer hope for a cure in this affliction.",2011 Dec 29,"Carter, Chris",Int J Alzheimers Dis,,,True
9104d87ad3991408937aa1e1739e7df0f51d01b0,PMC,"The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy",http://dx.doi.org/10.1371/journal.pone.0029608,PMC3256159,22247782,CC BY,"BACKGROUND: Filoviruses, including Ebola virus, are unusual in being filamentous animal viruses. Structural data on the arrangement, stoichiometry and organisation of the component molecules of filoviruses has until now been lacking, partially due to the need to work under level 4 biological containment. The present study provides unique insights into the structure of this deadly pathogen. METHODOLOGY AND PRINCIPAL FINDINGS: We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. We show that the helical Ebola virus inner nucleocapsid containing RNA and nucleoprotein is stabilized by an outer layer of VP24-VP35 bridges. Elucidation of the structure of the membrane-associated glycoprotein in its native state indicates that the putative receptor-binding site is occluded within the molecule, while a major neutralizing epitope is exposed on its surface proximal to the viral envelope. The matrix protein VP40 forms a regular lattice within the envelope, although its contacts with the nucleocapsid are irregular. CONCLUSIONS: The results of this study demonstrate a modular organization in Ebola virus that accommodates a well-ordered, symmetrical nucleocapsid within a flexible, tubular membrane envelope.",2012 Jan 11,"['Beniac, Daniel R.', 'Melito, Pasquale L.', 'deVarennes, Shauna L.', 'Hiebert, Shannon L.', 'Rabb, Melissa J.', 'Lamboo, Lindsey L.', 'Jones, Steven M.', 'Booth, Timothy F.']",PLoS One,,,True
693d0f533004851d03a1f38a336f6aa943ea2733,PMC,"Up-Regulation of Mcl-1 and Bak by Coronavirus Infection of Human, Avian and Animal Cells Modulates Apoptosis and Viral Replication",http://dx.doi.org/10.1371/journal.pone.0030191,PMC3256233,22253918,CC BY,"Virus-induced apoptosis and viral mechanisms that regulate this cell death program are key issues in understanding virus-host interactions and viral pathogenesis. Like many other human and animal viruses, coronavirus infection of mammalian cells induces apoptosis. In this study, the global gene expression profiles are first determined in IBV-infected Vero cells at 24 hours post-infection by Affymetrix array, using avian coronavirus infectious bronchitis virus (IBV) as a model system. It reveals an up-regulation at the transcriptional level of both pro-apoptotic Bak and pro-survival myeloid cell leukemia-1 (Mcl-1). These results were further confirmed both in vivo and in vitro, in IBV-infected embryonated chicken eggs, chicken fibroblast cells and mammalian cells at transcriptional and translational levels, respectively. Interestingly, the onset of apoptosis occurred earlier in IBV-infected mammalian cells silenced with short interfering RNA targeting Mcl-1 (siMcl-1), and was delayed in cells silenced with siBak. IBV progeny production and release were increased in infected Mcl-1 knockdown cells compared to similarly infected control cells, while the contrary was observed in infected Bak knockdown cells. Furthermore, IBV infection-induced up-regulation of GADD153 regulated the expression of Mcl-1. Inhibition of the mitogen-activated protein/extracellular signal-regulated kinase (MEK/ERK) and phosphoinositide 3-kinase (PI3K/Akt) signaling pathways by chemical inhibitors and knockdown of GADD153 by siRNA demonstrated the involvement of ER-stress response in regulation of IBV-induced Mcl-1 expression. These results illustrate the sophisticated regulatory strategies evolved by a coronavirus to modulate both virus-induced apoptosis and viral replication during its replication cycle.",2012 Jan 11,"['Zhong, Yanxin', 'Liao, Ying', 'Fang, Shouguo', 'Tam, James P.', 'Liu, Ding Xiang']",PLoS One,,,True
4e45a8379e00a6551b99dcb0c8ba91b7b358f853,PMC,"3D QSAR Pharmacophore Modeling, in Silico Screening, and Density Functional Theory (DFT) Approaches for Identification of Human Chymase Inhibitors",http://dx.doi.org/10.3390/ijms12129236,PMC3257128,22272131,CC BY,"Human chymase is a very important target for the treatment of cardiovascular diseases. Using a series of theoretical methods like pharmacophore modeling, database screening, molecular docking and Density Functional Theory (DFT) calculations, an investigation for identification of novel chymase inhibitors, and to specify the key factors crucial for the binding and interaction between chymase and inhibitors is performed. A highly correlating (r = 0.942) pharmacophore model (Hypo1) with two hydrogen bond acceptors, and three hydrophobic aromatic features is generated. After successfully validating “Hypo1”, it is further applied in database screening. Hit compounds are subjected to various drug-like filtrations and molecular docking studies. Finally, three structurally diverse compounds with high GOLD fitness scores and interactions with key active site amino acids are identified as potent chymase hits. Moreover, DFT study is performed which confirms very clear trends between electronic properties and inhibitory activity (IC(50)) data thus successfully validating “Hypo1” by DFT method. Therefore, this research exertion can be helpful in the development of new potent hits for chymase. In addition, the combinational use of docking, orbital energies and molecular electrostatic potential analysis is also demonstrated as a good endeavor to gain an insight into the interaction between chymase and inhibitors.",2011 Dec 12,"['Arooj, Mahreen', 'Thangapandian, Sundarapandian', 'John, Shalini', 'Hwang, Swan', 'Park, Jong Keun', 'Lee, Keun Woo']",Int J Mol Sci,,,True
1a5c7512b0e842a7b5f1d1511d0f035a0dbc3c25,PMC,SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b,http://dx.doi.org/10.1371/journal.pone.0029542,PMC3257236,22253733,CC BY,"BACKGROUND: The causative agent of severe acute respiratory syndrome, SARS coronavirus (SARS-CoV) genome encodes several unique group specific accessory proteins with unknown functions. Among them, accessory protein 3b (also known as ORF4) was lately identified as one of the viral interferon antagonist. Recently our lab uncovered a new role for 3b in upregulation of AP-1 transcriptional activity and its downstream genes. Thus, we believe that 3b might play an important role in SARS-CoV pathogenesis and therefore is of considerable interest. The current study aims at identifying novel host cellular interactors of the 3b protein. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using yeast two-hybrid and co-immunoprecipitation techniques, we have identified a host transcription factor RUNX1b (Runt related transcription factor, isoform b) as a novel interacting partner for SARS-CoV 3b protein. Chromatin immunoprecipitaion (ChIP) and reporter gene assays in 3b expressing jurkat cells showed recruitment of 3b on the RUNX1 binding element that led to an increase in RUNX1b transactivation potential on the IL2 promoter. Kinase assay and pharmacological inhibitor treatment implied that 3b also affect RUNX1b transcriptional activity by regulating its ERK dependent phosphorylation levels. Additionally, mRNA levels of MIP-1α, a RUNX1b target gene upregulated in SARS-CoV infected monocyte-derived dendritic cells, were found to be elevated in 3b expressing U937 monocyte cells. CONCLUSIONS/SIGNIFICANCE: These results unveil a novel interaction of SARS-CoV 3b with the host factor, RUNX1b, and speculate its physiological relevance in upregulating cytokines and chemokine levels in state of SARS virus infection.",2012 Jan 12,"['Varshney, Bhavna', 'Agnihotram, Sudhakar', 'Tan, Yee-Joo', 'Baric, Ralph', 'Lal, Sunil K.']",PLoS One,,,True
5566d234b7245b606a50f808fe09b5e3a4f04711,PMC,Henipavirus Neutralising Antibodies in an Isolated Island Population of African Fruit Bats,http://dx.doi.org/10.1371/journal.pone.0030346,PMC3257271,22253928,CC0,"Isolated islands provide valuable opportunities to study the persistence of viruses in wildlife populations, including population size thresholds such as the critical community size. The straw-coloured fruit bat, Eidolon helvum, has been identified as a reservoir for henipaviruses (serological evidence) and Lagos bat virus (LBV; virus isolation and serological evidence) in continental Africa. Here, we sampled from a remote population of E. helvum annobonensis fruit bats on Annobón island in the Gulf of Guinea to investigate whether antibodies to these viruses also exist in this isolated subspecies. Henipavirus serological analyses (Luminex multiplexed binding and inhibition assays, virus neutralisation tests and western blots) and lyssavirus serological analyses (LBV: modified Fluorescent Antibody Virus Neutralisation test, LBV and Mokola virus: lentivirus pseudovirus neutralisation assay) were undertaken on 73 and 70 samples respectively. Given the isolation of fruit bats on Annobón and their lack of connectivity with other populations, it was expected that the population size on the island would be too small to allow persistence of viruses that are thought to cause acute and immunising infections. However, the presence of antibodies against henipaviruses was detected using the Luminex binding assay and confirmed using alternative assays. Neutralising antibodies to LBV were detected in one bat using both assays. We demonstrate clear evidence for exposure of multiple individuals to henipaviruses in this remote population of E. helvum annobonensis fruit bats on Annobón island. The situation is less clear for LBV. Seroprevalences to henipaviruses and LBV in Annobón are notably different to those in E. helvum in continental locations studied using the same sampling techniques and assays. Whilst cross-sectional serological studies in wildlife populations cannot provide details on viral dynamics within populations, valuable information on the presence or absence of viruses may be obtained and utilised for informing future studies.",2012 Jan 12,"['Peel, Alison J.', 'Baker, Kate S.', 'Crameri, Gary', 'Barr, Jennifer A.', 'Hayman, David T. S.', 'Wright, Edward', 'Broder, Christopher C.', 'Fernández-Loras, Andrés', 'Fooks, Anthony R.', 'Wang, Lin-Fa', 'Cunningham, Andrew A.', 'Wood, James L. N.']",PLoS One,,,True
b7e0b1aeadb98920f56a14043d2f170833a31ef5,PMC,Perspectives on Immunoglobulins in Colostrum and Milk,http://dx.doi.org/10.3390/nu3040442,PMC3257684,22254105,CC BY,"Immunoglobulins form an important component of the immunological activity found in milk and colostrum. They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring. The mechanism of transfer varies among mammalian species. Cattle provide a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans. Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases. The use of colostrum or milk as a source of immunoglobulins, whether intended for the neonate of the species producing the secretion or for a different species, can be viewed in the context of the types of immunoglobulins in the secretion, the mechanisms by which the immunoglobulins are secreted, and the mechanisms by which the neonate or adult consuming the milk then gains immunological benefit. The stability of immunoglobulins as they undergo processing in the milk, or undergo digestion in the intestine, is an additional consideration for evaluating the value of milk immunoglobulins. This review summarizes the fundamental knowledge of immunoglobulins found in colostrum, milk, and immune milk.",2011 Apr 14,"['Hurley, Walter L.', 'Theil, Peter K.']",Nutrients,,,True
17bcc640fec147856a5d625a1d17970429665b65,PMC,Vaccination of influenza a virus decreases transmission rates in pigs,http://dx.doi.org/10.1186/1297-9716-42-120,PMC3258204,22185601,CC BY,"Limited information is available on the transmission and spread of influenza virus in pig populations with differing immune statuses. In this study we assessed differences in transmission patterns and quantified the spread of a triple reassortant H1N1 influenza virus in naïve and vaccinated pig populations by estimating the reproduction ratio (R) of infection (i.e. the number of secondary infections caused by an infectious individual) using a deterministic Susceptible-Infectious-Recovered (SIR) model, fitted on experimental data. One hundred and ten pigs were distributed in ten isolated rooms as follows: (i) non-vaccinated (NV), (ii) vaccinated with a heterologous vaccine (HE), and (iii) vaccinated with a homologous inactivated vaccine (HO). The study was run with multiple replicates and for each replicate, an infected non-vaccinated pig was placed with 10 contact pigs for two weeks and transmission of influenza evaluated daily by analyzing individual nasal swabs by RT-PCR. A statistically significant difference between R estimates was observed between vaccinated and non-vaccinated pigs (p < 0.05). A statistically significant reduction in transmission was observed in the vaccinated groups where R (95%CI) was 1 (0.39-2.09) and 0 for the HE and the HO groups respectively, compared to an R(o )value of 10.66 (6.57-16.46) in NV pigs (p < 0.05). Transmission in the HE group was delayed and variable when compared to the NV group and transmission could not be detected in the HO group. Results from this study indicate that influenza vaccines can be used to decrease susceptibility to influenza infection and decrease influenza transmission.",2011 Dec 20,"['Romagosa, Anna', 'Allerson, Matt', 'Gramer, Marie', 'Joo, Han Soo', 'Deen, John', 'Detmer, Susan', 'Torremorell, Montserrat']",Vet Res,,,True
fcf41a33dfcb8326a794806dc8bd7585c7e9e591,PMC,Cryptosporidium infection in a veal calf cohort in France: molecular characterization of species in a longitudinal study,http://dx.doi.org/10.1186/1297-9716-42-116,PMC3259045,22136667,CC BY,"Feces from 142 animals were collected on 15 farms in the region of Brittany, France. Each sample was directly collected from the rectum of the animal and identified with the ear tag number. Animals were sampled three times, at 5, 15 and 22 weeks of age. After DNA extraction from stool samples, nested PCR was performed to amplify partial 18S-rDNA and 60 kDa glycoprotein genes of Cryptosporidium. The parasite was detected on all farms. One hundred out of 142 calves (70.4%) were found to be parasitized by Cryptosporidium. Amplified fragments were sequenced for Cryptosporidium species identification and revealed the presence of C. parvum (43.8%), C. ryanae (28.5%), and C. bovis (27%). One animal was infected with Cryptosporidium ubiquitum. The prevalence of these species was related to the age of the animal. C. parvum caused 86.7% of Cryptosporidium infections in 5-week-old calves but only 1.7% in 15-week-old animals. The analysis of the results showed that animals could be infected successively by C. parvum, C. ryanae, and C. bovis for the study period. C. parvum gp60 genotyping identifies 6 IIa subtypes of which 74.5% were represented by IIaA15G2R1. This work confirms previous studies in other countries showing that zoonotic C. parvum is the dominant species seen in young calves.",2011 Dec 2,"['Follet, Jérôme', 'Guyot, Karine', 'Leruste, Hélène', 'Follet-Dumoulin, Anne', 'Hammouma-Ghelboun, Ourida', 'Certad, Gabriela', 'Dei-Cas, Eduardo', 'Halama, Patrice']",Vet Res,,,True
f85f1c88d5f92b9177f3c652fe643d7f13df947e,PMC,Rapid detection of wheat yellow mosaic virus by reverse transcription loop-mediated isothermal amplification,http://dx.doi.org/10.1186/1743-422X-8-550,PMC3260119,22185375,CC BY,"For the detection of wheat yellow mosaic virus (WYMV), we established a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method. Using Primer Explorer software, four sets of primers were designed and RT-LAMP assay reaction conditions were optimized. The RT-LAMP was performed at different times by four primer sets. Agarose gel analysis showed that WYMV could be detected after 30 min with the primer set III and after 45 min with the other three primer sets, both under the 80-min reaction time. RT-LAMP had the same results with the four primer sets, thus primer set III and 65°C for 80 min reaction were selected for virus detection. There was no significant different when avian myeloblastosis virus (AMV) and moloney murine leukemia virus (M-MLV) RT-LAMP with the four primer sets and M-MLV was chosen due to its relatively cheap price. The result on specificity showed that the assay could amplify WYMV specifically, and the sensitivity comparison showed that the RT-LAMP was 100 times more sensitive than conventional reverse-transcriptase-polymerase chain reaction (RT-PCR). Overall, RT-LAMP was found to be a simple, specific, sensitive, convenient and time-saving method for WYMV detection.",2011 Dec 20,"['Zhang, Zong-Ying', 'Liu, Xiao-Jun', 'Li, Da-Wei', 'Yu, Jia-Lin', 'Han, Cheng-Gui']",Virol J,,,True
98e52cb0b81f381ecd6138f73e6596de35d7566f,PMC,Human SCARB2-Mediated Entry and Endocytosis of EV71,http://dx.doi.org/10.1371/journal.pone.0030507,PMC3260287,22272359,CC BY,"Enterovirus (EV) 71 infection is known to cause hand-foot-and-mouth disease (HFMD) and in severe cases, induces neurological disorders culminating in fatality. An outbreak of EV71 in South East Asia in 1997 affected over 120,000 people and caused neurological disorders in a few individuals. The control of EV71 infection through public health interventions remains minimal and treatments are only symptomatic. Recently, human scavenger receptor class B, member 2 (SCARB2) has been reported to be a cellular receptor of EV71. We expressed human SCARB2 gene in NIH3T3 cells (3T3-SCARB2) to study the mechanisms of EV71 entry and infection. We demonstrated that human SCARB2 serves as a cellular receptor for EV71 entry. Disruption of expression of SCARB2 using siRNAs can interfere EV71 infection and subsequent inhibit the expression of viral capsid proteins in RD and 3T3-SCARB2 but not Vero cells. SiRNAs specific to clathrin or dynamin or chemical inhibitor of clathrin-mediated endocytosis were all capable of interfering with the entry of EV71 into 3T3-SCARB2 cells. On the other hand, caveolin specific siRNA or inhibitors of caveolae-mediated endocytosis had no effect, confirming that only clathrin-mediated pathway was involved in EV71 infection. Endocytosis of EV71 was also found to be pH-dependent requiring endosomal acidification and also required intact membrane cholesterol. In summary, the mechanism of EV71 entry through SCARB2 as the receptor for attachment, and its cellular entry is through a clathrin-mediated and pH-dependent endocytic pathway. This study on the receptor and endocytic mechanisms of EV71 infection is useful for the development of effective medications and prophylactic treatment against the enterovirus.",2012 Jan 17,"['Lin, Yi-Wen', 'Lin, Hsiang-Yin', 'Tsou, Yueh-Liang', 'Chitra, Ebenezer', 'Hsiao, Kuang-Nan', 'Shao, Hsiao-Yun', 'Liu, Chia-Chyi', 'Sia, Charles', 'Chong, Pele', 'Chow, Yen-Hung']",PLoS One,,,True
28b64c3ea5c13cbcaae132a45661fb8bf5c25c62,PMC,The Origin and Evolution of Variable Number Tandem Repeat of CLEC4M Gene in the Global Human Population,http://dx.doi.org/10.1371/journal.pone.0030268,PMC3261175,22279577,CC BY,"CLEC4M is a C-type lectin gene serving as cell adhesion receptor and pathogen recognition receptor. It recognizes several pathogens of important public health concern. In particular, a highly polymorphic variable number tandem repeat (VNTR) at the neck-region of CLEC4M had been associated with genetic predisposition to some infectious diseases. To gain insight into the origin and evolution of this VNTR in CLEC4M, we studied 21 Africans, 20 Middle Easterns, 35 Europeans, 38 Asians, 13 Oceania, and 18 Americans (a total of 290 chromosomes) from the (Human Genome Diversity Panel) HGDP-CEPH panel; these samples covered most of alleles of this VNTR locus present in human populations. We identified a limited number of haplotypes among the basic repeat subunits that is 69 base pairs in length. Only 8 haplotypes were found. Their sequence identities were determined in the 290 chromosomes. VNTR alleles of different repeat length (from 4 to 9 repeats) were analyzed for composition and orientation of these subunits. Our results showed that the subunit configuration of the same repeat number of VNTR locus from different populations were, in fact, virtually identical. It implies that most of the VNTR alleles existed before dispersion of modern humans outside Africa. Further analyses indicate that the present diversity profile of this locus in worldwide populations is generated from the effect of migration of different tribes and neutral evolution. Our findings do not support the hypothesis that the origin of the VNTR alleles were arisen by independent (separate) mutation events and caused by differential allele advantage and natural selection as suggested by previous report based on SNP data.",2012 Jan 18,"['Li, Hui', 'Wang, Jia-Xin', 'Wu, Dong-Dong', 'Wang, Hua-Wei', 'Tang, Nelson Leung-Sang', 'Zhang, Ya-Ping']",PLoS One,,,True
7cc24fe787282c1bc90ccbb2d9c2262a95b7504a,PMC,Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus,http://dx.doi.org/10.1371/journal.pone.0030328,PMC3261190,22279582,CC BY,"Swine influenza is an acute respiratory disease in pigs caused by swine influenza virus (SIV). Highly virulent SIV strains cause mortality of up to 10%. Importantly, pigs have long been considered “mixing vessels” that generate novel influenza viruses with pandemic potential, a constant threat to public health. Since its emergence in 2009 and subsequent pandemic spread, the pandemic (H1N1) 2009 (H1N1pdm) has been detected in pig farms, creating the risk of generating new reassortants and their possible infection of humans. Pathogenesis in SIV or H1N1pdm-infected pigs remains poorly characterized. Proinflammatory and antiviral cytokine responses are considered correlated with the intensity of clinical signs, and swine macrophages are found to be indispensible in effective clearance of SIV from pig lungs. In this study, we report a unique pattern of cytokine responses in swine macrophages infected with H1N1pdm. The roles of mitogen-activated protein (MAP) kinases in the regulation of the host responses were examined. We found that proinflammatory cytokines IL-6, IL-8, IL-10, and TNF-α were significantly induced and their induction was ERK1/2-dependent. IFN-β and IFN-inducible antiviral Mx and 2′5′-OAS were sharply induced, but the inductions were effectively abolished when ERK1/2 was inhibited. Induction of CCL5 (RANTES) was completely inhibited by inhibitors of ERK1/2 and JNK1/2, which appeared also to regulate FasL and TNF-α, critical for apoptosis in pig macrophages. We found that NFκB was activated in H1N1pdm-infected cells, but the activation was suppressed when ERK1/2 was inhibited, indicating there is cross-talk between MAP kinase and NFκB responses in pig macrophages. Our data suggest that MAP kinase may activate NFκB through the induction of RIG-1, which leads to the induction of IFN-β in swine macrophages. Understanding host responses and their underlying mechanisms may help identify venues for effective control of SIV and assist in prevention of future influenza pandemics.",2012 Jan 18,"['Gao, Wei', 'Sun, Wenkui', 'Qu, Bingqian', 'Cardona, Carol J.', 'Powell, Kira', 'Wegner, Marta', 'Shi, Yi', 'Xing, Zheng']",PLoS One,,,True
90a31cc826fade05b0a3670af7a5d47d6f972b07,PMC,Trending Now: Using Social Media to Predict and Track Disease Outbreaks,http://dx.doi.org/10.1289/ehp.120-a30,PMC3261963,22214548,CC0,,2012 Jan 1,"Schmidt, Charles W.",Environ Health Perspect,,,True
cf06138d477edd309f439ae40bf555d5bf63b173,PMC,Methods to infer transmission risk factors in complex outbreak data,http://dx.doi.org/10.1098/rsif.2011.0379,PMC3262428,21831890,CC BY,"Data collected during outbreaks are essential to better understand infectious disease transmission and design effective control strategies. But analysis of such data is challenging owing to the dependency between observations that is typically observed in an outbreak and to missing data. In this paper, we discuss strategies to tackle some of the ongoing challenges in the analysis of outbreak data. We present a relatively generic statistical model for the estimation of transmission risk factors, and discuss algorithms to estimate its parameters for different levels of missing data. We look at the problem of computational times for relatively large datasets and show how they can be reduced by appropriate use of discretization, sufficient statistics and some simple assumptions on the natural history of the disease. We also discuss approaches to integrate parametric model fitting and tree reconstruction methods in coherent statistical analyses. The methods are tested on both real and simulated datasets of large outbreaks in structured populations.",2012 Mar 7,"['Cauchemez, Simon', 'Ferguson, Neil M.']",J R Soc Interface,,,True
c46224620e6c2f039588f57d5133dedd75941da5,PMC,RNA-Seq Based Transcriptional Map of Bovine Respiratory Disease Pathogen “Histophilus somni 2336”,http://dx.doi.org/10.1371/journal.pone.0029435,PMC3262788,22276113,CC BY,"Genome structural annotation, i.e., identification and demarcation of the boundaries for all the functional elements in a genome (e.g., genes, non-coding RNAs, proteins and regulatory elements), is a prerequisite for systems level analysis. Current genome annotation programs do not identify all of the functional elements of the genome, especially small non-coding RNAs (sRNAs). Whole genome transcriptome analysis is a complementary method to identify “novel” genes, small RNAs, regulatory regions, and operon structures, thus improving the structural annotation in bacteria. In particular, the identification of non-coding RNAs has revealed their widespread occurrence and functional importance in gene regulation, stress and virulence. However, very little is known about non-coding transcripts in Histophilus somni, one of the causative agents of Bovine Respiratory Disease (BRD) as well as bovine infertility, abortion, septicemia, arthritis, myocarditis, and thrombotic meningoencephalitis. In this study, we report a single nucleotide resolution transcriptome map of H. somni strain 2336 using RNA-Seq method. The RNA-Seq based transcriptome map identified 94 sRNAs in the H. somni genome of which 82 sRNAs were never predicted or reported in earlier studies. We also identified 38 novel potential protein coding open reading frames that were absent in the current genome annotation. The transcriptome map allowed the identification of 278 operon (total 730 genes) structures in the genome. When compared with the genome sequence of a non-virulent strain 129Pt, a disproportionate number of sRNAs (∼30%) were located in genomic region unique to strain 2336 (∼18% of the total genome). This observation suggests that a number of the newly identified sRNAs in strain 2336 may be involved in strain-specific adaptations.",2012 Jan 20,"['Kumar, Ranjit', 'Lawrence, Mark L.', 'Watt, James', 'Cooksey, Amanda M.', 'Burgess, Shane C.', 'Nanduri, Bindu']",PLoS One,,,True
14b4d32ff078c4db9661a587e43a30a7bf227ed9,PMC,The Paradox of Feline Coronavirus Pathogenesis: A Review,http://dx.doi.org/10.1155/2011/109849,PMC3265210,22312333,CC BY,"Feline coronavirus (FCoV) is an enveloped single-stranded RNA virus, of the family Coronaviridae and the order Nidovirales. FCoV is an important pathogen of wild and domestic cats and can cause a mild or apparently symptomless enteric infection, especially in kittens. FCoV is also associated with a lethal, systemic disease known as feline infectious peritonitis (FIP). Although the precise cause of FIP pathogenesis remains unclear, some hypotheses have been suggested. In this review we present results from different FCoV studies and attempt to elucidate existing theories on the pathogenesis of FCoV infection.",2011 Aug 21,"['Myrrha, Luciana Wanderley', 'Silva, Fernanda Miquelitto Figueira', 'Peternelli, Ethel Fernandes de Oliveira', 'Junior, Abelardo Silva', 'Resende, Maurício', 'de Almeida, Márcia Rogéria']",Adv Virol,,,True
bd44d72a9c41b1c382bd180da10a1f7ef38d2d56,PMC,Retargeting of Viruses to Generate Oncolytic Agents,http://dx.doi.org/10.1155/2012/798526,PMC3265223,22312365,CC BY,"Oncolytic virus therapy is based on the ability of viruses to effectively infect and kill tumor cells without destroying the normal tissues. While some viruses seem to have a natural preference for tumor cells, most viruses require the modification of their tropism to specifically enter and replicate in such cells. This review aims to describe the transductional targeting strategies currently employed to specifically redirect viruses towards surface receptors on tumor cells. Three major strategies can be distinguished; they involve (i) the incorporation of new targeting specificity into a viral surface protein, (ii) the incorporation of a scaffold into a viral surface protein to allow the attachment of targeting moieties, and (iii) the use of bispecific adapters to mediate targeting of a virus to a specified moiety on a tumor cell. Of each strategy key features, advantages and limitations are discussed and examples are given. Because of their potential to cause sustained, multiround infection—a desirable characteristic for eradicating tumors—particular attention is given to viruses engineered to become self-targeted by the genomic expression of a bispecific adapter protein.",2012 Nov 14,"['Verheije, M. H.', 'Rottier, P. J. M.']",Adv Virol,,,True
de01b5c28a44e4d80b38e389342275d0353673e7,PMC,"Human Coronaviruses HCoV-NL63 and HCoV-HKU1 in Hospitalized Children with Acute Respiratory Infections in Beijing, China",http://dx.doi.org/10.1155/2011/129134,PMC3265292,22315599,CC BY,"The human coronaviruses (HCoVs) HCoV-NL63 and HCoV-HKU1 are two recently discovered coronaviruses that circulate widely and are associated with acute respiratory infections (ARI). We detected HCoV-NL63 and HCoV-HKU1 in specimens collected from May 2008 to March 2010 from patients with ARI aged <7.75 years of age attending the Beijing Children's Hospital. Thirty-two (8.4%) and 57 (14.9%) of 382 specimens tested positive for HCoV-NL63 and HCoV-HKU1, respectively, by real-time RT-PCR. Use of a Luminex xTAG RVP Fast kit showed that coinfection with respiratory syncytial virus and parainfluenza 3 virus was common among patients infected with either virus type. In HCoV-HKU1-infected patients, the predominant clinical symptoms were cough, fever, and expectoration. In HCoV-NL63-infected patients they were cough, fever, and rhinorrhea. Phylogenetic studies showed that the HCoV-HKU1 nucleoprotein gene was relatively conserved compared to NCBI reference sequences, while the 1ab gene of HCoV-NL63 showed more variation.",2011 Jul 21,"['Cui, Li-Jin', 'Zhang, Chen', 'Zhang, Ting', 'Lu, Rou-Jian', 'Xie, Zheng-De', 'Zhang, Ling-Lin', 'Liu, Chuan-Yan', 'Zhou, Wei-Min', 'Ruan, Li', 'Ma, Xue-Jun', 'Tan, Wen-Jie']",Adv Virol,,,True
551042ee7c8e1bd9f237a51c666376205c89bb3e,PMC,The Evolutionary Processes of Canine Coronaviruses,http://dx.doi.org/10.1155/2011/562831,PMC3265307,22315601,CC BY,"Since the first identification of the virus in 1971, the disease caused by canine coronavirus (CCoV) has not been adequately investigated, and the role that the virus plays in canine enteric illness has not been well established. Only after the emergence in 2002 of SARS in human has new attention been focused on coronaviruses. As a consequence of the relatively high mutation frequency of RNA-positive stranded viruses, CCoV has evolved and, with the biomolecular techniques developed over the last two decades, new virus strains, serotypes, and subtypes have been identified in infected dogs. Considering the widespread nature of CCoV infections among dog populations, several studies have been carried out, focusing upon the epidemiological relevance of these viruses and underlining the need for further investigation into the biology of CCoVs and into the pathogenetic role of the infections. This paper reports the evolutionary processes of CCoVs with a note onto recent diagnostic methods.",2011 Jul 7,"Pratelli, Annamaria",Adv Virol,,,True
d9eb8ffffee8147c850b00f613a1978c18505580,PMC,Feline and Canine Coronaviruses: Common Genetic and Pathobiological Features,http://dx.doi.org/10.1155/2011/609465,PMC3265309,22312347,CC BY,"A new human coronavirus responsible for severe acute respiratory syndrome (SARS) was identified in 2003, which raised concern about coronaviruses as agents of serious infectious disease. Nevertheless, coronaviruses have been known for about 50 years to be major agents of respiratory, enteric, or systemic infections of domestic and companion animals. Feline and canine coronaviruses are widespread among dog and cat populations, sometimes leading to the fatal diseases known as feline infectious peritonitis (FIP) and pantropic canine coronavirus infection in cats and dogs, respectively. In this paper, different aspects of the genetics, host cell tropism, and pathogenesis of the feline and canine coronaviruses (FCoV and CCoV) will be discussed, with a view to illustrating how study of FCoVs and CCoVs can improve our general understanding of the pathobiology of coronaviruses.",2011 Jul 31,"Le Poder, Sophie",Adv Virol,,,True
79284efbde971538024ccbe888fa90bcd515d45c,PMC,The Effects of Temperature and Relative Humidity on the Viability of the SARS Coronavirus,http://dx.doi.org/10.1155/2011/734690,PMC3265313,22312351,CC BY,"The main route of transmission of SARS CoV infection is presumed to be respiratory droplets. However the virus is also detectable in other body fluids and excreta. The stability of the virus at different temperatures and relative humidity on smooth surfaces were studied. The dried virus on smooth surfaces retained its viability for over 5 days at temperatures of 22–25°C and relative humidity of 40–50%, that is, typical air-conditioned environments. However, virus viability was rapidly lost (>3 log(10)) at higher temperatures and higher relative humidity (e.g., 38°C, and relative humidity of >95%). The better stability of SARS coronavirus at low temperature and low humidity environment may facilitate its transmission in community in subtropical area (such as Hong Kong) during the spring and in air-conditioned environments. It may also explain why some Asian countries in tropical area (such as Malaysia, Indonesia or Thailand) with high temperature and high relative humidity environment did not have major community outbreaks of SARS.",2011 Oct 1,"['Chan, K. H.', 'Peiris, J. S. Malik', 'Lam, S. Y.', 'Poon, L. L. M.', 'Yuen, K. Y.', 'Seto, W. H.']",Adv Virol,,,True
14c756dfe065a0ed1ff950195576f8975d209c93,PMC,Effect modification of environmental factors on influenza-associated mortality: a time-series study in two Chinese cities,http://dx.doi.org/10.1186/1471-2334-11-342,PMC3265445,22168284,CC BY,"BACKGROUND: Environmental factors have been associated with transmission and survival of influenza viruses but no studies have ever explored the role of environmental factors on severity of influenza infection. METHODS: We applied a Poisson regression model to the mortality data of two Chinese metropolitan cities located within the subtropical zone, to calculate the influenza associated excess mortality risks during the periods with different levels of temperature and humidity. RESULTS: The results showed that high absolute humidity (measured by vapor pressure) was significantly (p < 0.05) associated with increased risks of all-cause and cardiorespiratory deaths, but not with increased risks of pneumonia and influenza deaths. The association between absolute humidity and mortality risks was found consistent among the two cities. An increasing pattern of influenza associated mortality risks was also found across the strata of low to high relative humidity, but the results were less consistent for temperature. CONCLUSIONS: These findings highlight the need for people with chronic cardiovascular and respiratory diseases to take extra caution against influenza during hot and humid days in the subtropics and tropics.",2011 Dec 14,"['Yang, Lin', 'Chen, Ping Yan', 'He, Jian Feng', 'Chan, King Pan', 'Ou, Chun Quan', 'Deng, Ai Ping', 'Malik Peiris, JS', 'Wong, Chit Ming']",BMC Infect Dis,,,True
41546fbae5ea1a9c511d17fa9d9b583f944eda95,PMC,Genome Wide Association Identifies PPFIA1 as a Candidate Gene for Acute Lung Injury Risk Following Major Trauma,http://dx.doi.org/10.1371/journal.pone.0028268,PMC3266233,22295056,CC BY,"Acute Lung Injury (ALI) is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA) approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1), we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs) at p<0.01 to a replication phase (Phase 2) comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3) using expression quantitative trait loci (eQTL) analyses in stimulated B-lymphoblastoid cell lines (B-LCL) in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021). PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi-center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research.",2012 Jan 25,"['Christie, Jason D.', 'Wurfel, Mark M.', 'Feng, Rui', ""O'Keefe, Grant E."", 'Bradfield, Jonathan', 'Ware, Lorraine B.', 'Christiani, David C.', 'Calfee, Carolyn S.', 'Cohen, Mitchell J.', 'Matthay, Michael', 'Meyer, Nuala J.', 'Kim, Cecilia', 'Li, Mingyao', 'Akey, Joshua', 'Barnes, Kathleen C.', 'Sevransky, Jonathan', 'Lanken, Paul N.', 'May, Addison K.', 'Aplenc, Richard', 'Maloney, James P.', 'Hakonarson, Hakon', None]",PLoS One,,,True
84db97911a7abce47876c5732ac570d78f253aaa,PMC,One Health concept for strengthening public health surveillance and response through Field Epidemiology and Laboratory Training in Ghana,,PMC3266674,22359694,CC BY,"The lack of highly trained field epidemiologists in the public health system in Ghana has been known since the 1970s when the Planning Unit was established in the Ghana Ministry of Health. When the Public Health School was started in 1994, the decision was taken to develop a 1 academic-year general MPH course. The persisting need for well-trained epidemiologists to support the public health surveillance, outbreak investigation and response system made the development of the Field Epidemiology and Laboratory Training Programme (FELTP) a national priority. The School of Public health and the Ministry of Health therefore requested the technical and financial assistance of the United States Centers for Disease Control and Prevention (CDC) in organizing the Programme. The collaboration started by organizing short courses in disease outbreak investigations and response for serving Ghana Health Service staff. The success of the short courses led to development of the FELTP. By October 2007, the new FELTP curriculum for the award of a Masters of Philosophy in Applied Epidemiology and Disease Control was approved by the Academic Board of the University of Ghana and the programme started that academic year. Since then five cohorts of 37 residents have been enrolled in the two tracks of the programme. They consist of 12 physicians, 12 veterinarians and 13 laboratory scientists. The first two cohorts of 13 residents have graduated. The third cohort of seven has submitted dissertations and is awaiting the results. The fourth cohort has started the second year of field placement while the fifth cohort has just started the first semester. The field activities of the graduates have included disease outbreak investigations and response, evaluation of disease surveillance systems at the national level and analysis of datasets on diseases at the regional level. The residents have made a total of 25 oral presentations and 39 poster presentations at various regional and global scientific conferences. The Ghana FELTP (GFELTP) has promoted the introduction of the One Health concept into FELTP. It hosted the first USAID–supported workshop in West Africa to further integrate and strengthen collaboration of the animal and human health sectors in the FETP model. GFELTP has also taken the lead in hosting the first AFENET Center for Training in Public Health Leadership and Management, through which the short course on Management for Improving Public Health Interventions was developed for AFENET member countries. The GFELTP pre-tested the Integrated Avian Influenza Outbreak and Pandemic Influenza course in preparation for introducing the materials into the curriculum of other FELTP in the network. The leadership positions to which the graduates of the program have been appointed in the human and animal Public Health Services, improvement in disease surveillance, outbreak investigation and response along with the testimony of the health authorities about their appreciation of the outputs of the graduates at various fora, is a strong indication that the GFELTP is meeting its objectives.",2011 Dec 14,"['Wurapa, Frederick', 'Afari, Ebenezer', 'Ohuabunwo, Chima', 'Sackey, Samuel', 'Clerk, Christine', 'Kwadje, Simon', 'Yebuah, Nathaniel', 'Amankwa, Joseph', 'Amofah, George', 'Appiah-Denkyira, Ebenezer']",Pan Afr Med J,,,True
007bf75961da42a7e0cc8e2855e5c208a5ec65c1,PMC,The Murine Coronavirus Hemagglutinin-esterase Receptor-binding Site: A Major Shift in Ligand Specificity through Modest Changes in Architecture,http://dx.doi.org/10.1371/journal.ppat.1002492,PMC3266934,22291594,CC BY,"The hemagglutinin-esterases (HEs), envelope glycoproteins of corona-, toro- and orthomyxoviruses, mediate reversible virion attachment to O-acetylated sialic acids (O-Ac-Sias). They do so through concerted action of distinct receptor-binding (“lectin”) and receptor-destroying sialate O-acetylesterase (”esterase”) domains. Most HEs target 9-O-acetylated Sias. In one lineage of murine coronaviruses, however, HE esterase substrate and lectin ligand specificity changed dramatically as these viruses evolved to use 4-O-acetylated Sias instead. Here we present the crystal structure of the lectin domain of mouse hepatitis virus (MHV) strain S HE, resolved both in its native state and in complex with a receptor analogue. The data show that the shift from 9-O- to 4-O-Ac-Sia receptor usage primarily entailed a change in ligand binding topology and, surprisingly, only modest changes in receptor-binding site architecture. Our findings illustrate the ease with which viruses can change receptor-binding specificity with potential consequences for host-, organ and/or cell tropism, and for pathogenesis.",2012 Jan 26,"['Langereis, Martijn A.', 'Zeng, Qinghong', 'Heesters, Balthasar', 'Huizinga, Eric G.', 'de Groot, Raoul J.']",PLoS Pathog,,,True
3a6f6369bb9df09d06938f9ef8fdceb72de53a21,PMC,"Detection of human bocavirus from children and adults with acute respiratory tract illness in Guangzhou, southern China",http://dx.doi.org/10.1186/1471-2334-11-345,PMC3267697,22168387,CC BY,"BACKGROUND: Human bocavirus (HBoV) is a newly discovered parvovirus associated with acute respiratory tract illness (ARTI) and gastrointestinal illness. Our study is the first to analyze the characteristics of HBoV-positive samples from ARTI patients with a wide age distribution from Guangzhou, southern China. METHODS: Throat swabs (n=2811) were collected and analyzed from children and adults with ARTI over a 13-month period. The HBoV complete genome from a 60 year-old female patient isolate was also determined. RESULTS: HBoV DNA was detected in 65/2811 (2.3%) samples, of which 61/1797 were from children (<18 years old) and 4/1014 from adults (≥18 years old). Seasonal peaks of 4.8% and 7.7% were detected in May and June, respectively. 28 of 65 (43.1%) HBoV-positive samples were co-detected with 11/16 other potential pathogens. Mycoplasma pneumoniae had the highest frequency of 16.9% (11/65). Upper and lower respiratory tract illness were common symptoms, with 19/65 (29.2%) patients diagnosed with pneumonia by chest radiography. All four adult patients had systemic influenza-like symptoms. Phylogenetic analysis of the complete genome revealed a close relationship with other HBoVs, and a more distant relationship with HBoV2 and HBoV3. CONCLUSIONS: HBoV was detected from children and adults with ARTI from Guangzhou, southern China. Elderly people were also susceptive to HBoV. A single lineage of HBoV was detected among a wide age distribution of patients with ARTI.",2011 Dec 14,"['Liu, Wen-Kuan', 'Chen, De-Hui', 'Liu, Qian', 'Liang, Huan-Xi', 'Yang, Zi-Feng', 'Qin, Sheng', 'Zhou, Rong']",BMC Infect Dis,,,True
ce88c461bd735cb67a9a7f6dc4d3ec1418d7dffb,PMC,Low usage of government healthcare facilities for acute respiratory infections in guatemala: implications for influenza surveillance,http://dx.doi.org/10.1186/1471-2458-11-885,PMC3267779,22111590,CC BY,"BACKGROUND: Sentinel surveillance for severe acute respiratory infections in hospitals and influenza-like illness in ambulatory clinics is recommended to assist in global pandemic influenza preparedness. Healthcare utilization patterns will affect the generalizability of data from sentinel sites and the potential to use them to estimate burden of disease. The objective of this study was to measure healthcare utilization patterns in Guatemala to inform the establishment of a sentinel surveillance system for influenza and other respiratory infections, and allow estimation of disease burden. METHODS: We used a stratified, two-stage cluster survey sample to select 1200 households from the Department of Santa Rosa. Trained interviewers screened household residents for self-reported pneumonia in the last year and influenza-like illness (ILI) in the last month and asked about healthcare utilization for each illness episode. RESULTS: We surveyed 1131 (94%) households and 5449 residents between October and December 2006 and identified 323 (6%) cases of pneumonia and 628 (13%) cases of ILI. Treatment for pneumonia outside the home was sought by 92% of the children <5 years old and 73% of the persons aged five years and older. For both children <5 years old (53%) and persons aged five years and older (31%) who reported pneumonia, private clinics were the most frequently reported source of care. For ILI, treatment was sought outside the home by 81% of children <5 years old and 65% of persons aged five years and older. Government ambulatory clinics were the most frequently sought source of care for ILI both for children <5 years old (41%) and persons aged five years and older (36%). CONCLUSIONS: Sentinel surveillance for influenza and other respiratory infections based in government health facilities in Guatemala will significantly underestimate the burden of disease. Adjustment for healthcare utilization practices will permit more accurate estimation of the incidence of influenza and other respiratory pathogens in the community.",2011 Nov 24,"['Lindblade, Kim A', 'Johnson, April J', 'Arvelo, Wences', 'Zhang, Xingyou', 'Jordan, Hannah T', 'Reyes, Lissette', 'Fry, Alicia M', 'Padilla, Norma']",BMC Public Health,,,True
2f8012db8f2100bb1876e19722d6c131849e2315,PMC,Coronavirus Papain-like Proteases Negatively Regulate Antiviral Innate Immune Response through Disruption of STING-Mediated Signaling,http://dx.doi.org/10.1371/journal.pone.0030802,PMC3270028,22312431,CC BY,"Viruses have evolved elaborate mechanisms to evade or inactivate the complex system of sensors and signaling molecules that make up the host innate immune response. Here we show that human coronavirus (HCoV) NL63 and severe acute respiratory syndrome (SARS) CoV papain-like proteases (PLP) antagonize innate immune signaling mediated by STING (stimulator of interferon genes, also known as MITA/ERIS/MYPS). STING resides in the endoplasmic reticulum and upon activation, forms dimers which assemble with MAVS, TBK-1 and IKKε, leading to IRF-3 activation and subsequent induction of interferon (IFN). We found that expression of the membrane anchored PLP domain from human HCoV-NL63 (PLP2-TM) or SARS-CoV (PLpro-TM) inhibits STING-mediated activation of IRF-3 nuclear translocation and induction of IRF-3 dependent promoters. Both catalytically active and inactive forms of CoV PLPs co-immunoprecipitated with STING, and viral replicase proteins co-localize with STING in HCoV-NL63-infected cells. Ectopic expression of catalytically active PLP2-TM blocks STING dimer formation and negatively regulates assembly of STING-MAVS-TBK1/IKKε complexes required for activation of IRF-3. STING dimerization was also substantially reduced in cells infected with SARS-CoV. Furthermore, the level of ubiquitinated forms of STING, RIG-I, TBK1 and IRF-3 are reduced in cells expressing wild type or catalytic mutants of PLP2-TM, likely contributing to disruption of signaling required for IFN induction. These results describe a new mechanism used by CoVs in which CoV PLPs negatively regulate antiviral defenses by disrupting the STING-mediated IFN induction.",2012 Feb 1,"['Sun, Li', 'Xing, Yaling', 'Chen, Xiaojuan', 'Zheng, Yang', 'Yang, Yudong', 'Nichols, Daniel B.', 'Clementz, Mark A.', 'Banach, Bridget S.', 'Li, Kui', 'Baker, Susan C.', 'Chen, Zhongbin']",PLoS One,,,True
989be59a0cd5354610ff80be6e50fa6617c077bf,PMC,Protective Role of the ACE2/Ang-(1–9) Axis in Cardiovascular Remodeling,http://dx.doi.org/10.1155/2012/594361,PMC3270559,22315665,CC BY,"Despite reduction in cardiovascular (CV) events and end-organ damage with the current pharmacologic strategies, CV disease remains the primary cause of death in the world. Pharmacological therapies based on the renin angiotensin system (RAS) blockade are used extensively for the treatment of hypertension, heart failure, and CV remodeling but in spite of their success the prevalence of end-organ damage and residual risk remain still high. Novel approaches must be discovered for a more effective treatment of residual CV remodeling and risk. The ACE2/Ang-(1–9) axis is a new and important target to counterbalance the vasoconstrictive/proliferative RAS axis. Ang-(1–9) is hydrolyzed slower than Ang-(1–7) and is able to bind the Ang II type 2 receptor. We review here the current experimental evidence suggesting that activation of the ACE2/Ang-(1–9) axis protects the heart and vessels (and possibly the kidney) from adverse cardiovascular remodeling in hypertension as well as in heart failure.",2012 Jan 19,"['Ocaranza, María Paz', 'Jalil, Jorge E.']",Int J Hypertens,,,True
6652151e876145926c6b4c6d683346811588bdfa,PMC,Antiviral activity of four types of bioflavonoid against dengue virus type-2,http://dx.doi.org/10.1186/1743-422X-8-560,PMC3271998,22201648,CC BY,"BACKGROUND: Dengue is a major mosquito-borne disease currently with no effective antiviral or vaccine available. Effort to find antivirals for it has focused on bioflavonoids, a plant-derived polyphenolic compounds with many potential health benefits. In the present study, antiviral activity of four types of bioflavonoid against dengue virus type -2 (DENV-2) in Vero cell was evaluated. Anti-dengue activity of these compounds was determined at different stages of DENV-2 infection and replication cycle. DENV replication was measured by Foci Forming Unit Reduction Assay (FFURA) and quantitative RT-PCR. Selectivity Index value (SI) was determined as the ratio of cytotoxic concentration 50 (CC(50)) to inhibitory concentration 50 (IC(50)) for each compound. RESULTS: The half maximal inhibitory concentration (IC(50)) of quercetin against dengue virus was 35.7 μg mL(-1 )when it was used after virus adsorption to the cells. The IC(50 )decreased to 28.9 μg mL(-1 )when the cells were treated continuously for 5 h before virus infection and up to 4 days post-infection. The SI values for quercetin were 7.07 and 8.74 μg mL(-1), respectively, the highest compared to all bioflavonoids studied. Naringin only exhibited anti-adsorption effects against DENV-2 with IC(50 )= 168.2 μg mL(-1 )and its related SI was 1.3. Daidzein showed a weak anti-dengue activity with IC(50 )= 142.6 μg mL(-1 )when the DENV-2 infected cells were treated after virus adsorption. The SI value for this compound was 1.03. Hesperetin did not exhibit any antiviral activity against DENV-2. The findings obtained from Foci Forming Unit Reduction Assay (FFURA) were corroborated by findings of the qRT-PCR assays. Quercetin and daidzein (50 μg mL(-1)) reduced DENV-2 RNA levels by 67% and 25%, respectively. There was no significant inhibition of DENV-2 RNA levels with naringin and hesperetin. CONCLUSION: Results from the study suggest that only quercetin demonstrated significant anti-DENV-2 inhibitory activities. Other bioflavonoids, including daidzein, naringin and hesperetin showed minimal to no significant inhibition of DENV-2 virus replication. These findings, together with those previously reported suggest that select group of bioflavonoids including quercetin and fisetin, exhibited significant inhibitory activities against dengue virus. This group of flavonoids, flavonol, could be investigated further to discover the common mechanisms of inhibition of dengue virus replication.",2011 Dec 28,"['Zandi, Keivan', 'Teoh, Boon-Teong', 'Sam, Sing-Sin', 'Wong, Pooi-Fong', 'Mustafa, Mohd Rais', 'AbuBakar, Sazaly']",Virol J,,,True
880b3f24a1f3678dd29cb446dae24298863b8676,PMC,New Cardiovascular and Pulmonary Therapeutic Strategies Based on the Angiotensin-Converting Enzyme 2/Angiotensin-(1–7)/Mas Receptor Axis,http://dx.doi.org/10.1155/2012/147825,PMC3272817,22319643,CC BY,"Angiotensin (Ang)-(1–7) is now recognized as a biologically active component of the renin-angiotensin system (RAS). The discovery of the angiotensin-converting enzyme homologue ACE2 revealed important metabolic pathways involved in the Ang-(1–7) synthesis. This enzyme can form Ang-(1–7) from Ang II or less efficiently through hydrolysis of Ang I to Ang-(1–9) with subsequent Ang-(1–7) formation. Additionally, it is well established that the G protein-coupled receptor Mas is a functional ligand site for Ang-(1–7). The axis formed by ACE2/Ang-(1–7)/Mas represents an endogenous counter regulatory pathway within the RAS whose actions are opposite to the vasoconstrictor/proliferative arm of the RAS constituted by ACE/Ang II/AT(1) receptor. In this review we will discuss recent findings concerning the biological role of the ACE2/Ang-(1–7)/Mas arm in the cardiovascular and pulmonary system. Also, we will highlight the initiatives to develop potential therapeutic strategies based on this axis.",2012 Jan 26,"['Ferreira, Anderson J.', 'Murça, Tatiane M.', 'Fraga-Silva, Rodrigo A.', 'Castro, Carlos Henrique', 'Raizada, Mohan K.', 'Santos, Robson A. S.']",Int J Hypertens,,,True
5a1ae510c59da66b27b5a5a8adf78b252303f9f2,PMC,Fighting Misconceptions to Improve Compliance with Influenza Vaccination among Health Care Workers: An Educational Project,http://dx.doi.org/10.1371/journal.pone.0030670,PMC3273463,22328920,CC BY,"The compliance with influenza vaccination is poor among health care workers (HCWs) due to misconceptions about safety and effectiveness of influenza vaccine. We proposed an educational prospective study to demonstrate to HCWs that influenza vaccine is safe and that other respiratory viruses (RV) are the cause of respiratory symptoms in the months following influenza vaccination. 398 HCWs were surveyed for adverse events (AE) occurring within 48 h of vaccination. AE were reported by 30% of the HCWs. No severe AE was observed. A subset of 337 HCWs was followed up during four months, twice a week, for the detection of respiratory symptoms. RV was diagnosed by direct immunofluorescent assay (DFA) and real time PCR in symptomatic HCWs. Influenza A was detected in five episodes of respiratory symptoms (5.3%) and other RV in 26 (27.9%) episodes. The incidence density of influenza and other RV was 4.3 and 10.8 episodes per 100 HCW-month, respectively. The educational nature of the present study may persuade HCWs to develop a more positive attitude to influenza vaccination.",2012 Feb 6,"['Couto, Carla R.', 'Pannuti, Cláudio S.', 'Paz, José P.', 'Fink, Maria C. D.', 'Machado, Alessandra A.', 'de Marchi, Michela', 'Machado, Clarisse M.']",PLoS One,,,True
56feb53034b99302ba30fa1c3e2042b2118fe6cb,PMC,"Systematic screening for novel, serologically reactive Hepatitis E Virus epitopes",http://dx.doi.org/10.1186/1743-422X-9-28,PMC3274478,22269698,CC BY,"BACKGROUND: The National Institutes of Health classified Hepatitis E as an emerging disease since Hepatitis E Virus (HEV) is the major cause of acute hepatitis in developing countries. Interestingly, an increasing number of sporadic cases of HEV infections are described in industrialized countries as zoonosis from domestic livestock. Despite the increasing relevance of this pathogen in clinical virology, commercial antibody assays are mainly based on fragments of HEV open reading frame (ORF) 2 and ORF3. The largest ORF1 (poly-)protein, however, is not part of current testing formats. METHODS: From a synthesized full length HEV genotype 1 cDNA-bank we constructed a complete HEV gene library consisting of 15 respective HEV ORF domains. After bacterial expression and purification of nine recombinant HEV proteins under denaturating conditions serum profiling experiments using 55 sera from patients with known infection status were performed in microarray format. SPSS software assessed the antigenic potential of these nine ORF domains in comparison to seven commercial HEV antigens (genotype 1 and 3) by performing receiver operator characteristics, logistic regression and correlation analysis. RESULTS: HEV antigens produced with our method for serum profiling experiments exhibit the same quality and characteristics as commercial antigens. Serum profiling experiments detected Y, V and X domains as ORF1-antigens with potentially comparable diagnostic significance as the well established epitopes of ORF2 and ORF3. However no obvious additional increase in sensitivity or specificity was achieved in diagnostic testing as revealed by bioinformatic analysis. Additionally we found that the C-terminal domain of the potential transmembrane protein ORF3 is responsible for IgG and IgM seroreactivity. Data suggest that there might be a genotype specific seroreactivity of homologous ORF2-antigens. CONCLUSIONS: The diagnostic value of identified ORF1 epitopes might not necessarily improve sensitivity and specificity, but broaden the overall quality of existing test systems. ORF2 and ORF3-antigens are still commonly used in diagnostic assays and possibly hold the potential to serologically differentiate between genotype 1 and 3 infections. Our systematic approach is a suitable method to investigate HEV domains for their serologic antigenicity. Epitope screening of native viral domains could be a preferable tool in developing new serologic test components.",2012 Jan 23,"['Osterman, Andreas', 'Vizoso Pinto, Maria Guadalupe', 'Haase, Rudolf', 'Nitschko, Hans', 'Jäger, Simone', 'Sander, Michaela', 'Motz, Manfred', 'Mohn, Ulrich', 'Baiker, Armin']",Virol J,,,True
9692bb55e1e2eec083333ee2139137e6ddf3a4d8,PMC,Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing,http://dx.doi.org/10.1371/journal.pntd.0001485,PMC3274504,22347512,CC BY,"Dengue virus is an emerging infectious agent that infects an estimated 50–100 million people annually worldwide, yet current diagnostic practices cannot detect an etiologic pathogen in ∼40% of dengue-like illnesses. Metagenomic approaches to pathogen detection, such as viral microarrays and deep sequencing, are promising tools to address emerging and non-diagnosable disease challenges. In this study, we used the Virochip microarray and deep sequencing to characterize the spectrum of viruses present in human sera from 123 Nicaraguan patients presenting with dengue-like symptoms but testing negative for dengue virus. We utilized a barcoding strategy to simultaneously deep sequence multiple serum specimens, generating on average over 1 million reads per sample. We then implemented a stepwise bioinformatic filtering pipeline to remove the majority of human and low-quality sequences to improve the speed and accuracy of subsequent unbiased database searches. By deep sequencing, we were able to detect virus sequence in 37% (45/123) of previously negative cases. These included 13 cases with Human Herpesvirus 6 sequences. Other samples contained sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae families. In some cases, the putative viral sequences were virtually identical to known viruses, and in others they diverged, suggesting that they may derive from novel viruses. These results demonstrate the utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness.",2012 Feb 7,"['Yozwiak, Nathan L.', 'Skewes-Cox, Peter', 'Stenglein, Mark D.', 'Balmaseda, Angel', 'Harris, Eva', 'DeRisi, Joseph L.']",PLoS Negl Trop Dis,,,True
71d23a3d11c102af8346110435fc8e188665e832,PMC,Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing,http://dx.doi.org/10.1371/journal.pntd.0001485,PMC3274504,22347512,CC BY,"Dengue virus is an emerging infectious agent that infects an estimated 50–100 million people annually worldwide, yet current diagnostic practices cannot detect an etiologic pathogen in ∼40% of dengue-like illnesses. Metagenomic approaches to pathogen detection, such as viral microarrays and deep sequencing, are promising tools to address emerging and non-diagnosable disease challenges. In this study, we used the Virochip microarray and deep sequencing to characterize the spectrum of viruses present in human sera from 123 Nicaraguan patients presenting with dengue-like symptoms but testing negative for dengue virus. We utilized a barcoding strategy to simultaneously deep sequence multiple serum specimens, generating on average over 1 million reads per sample. We then implemented a stepwise bioinformatic filtering pipeline to remove the majority of human and low-quality sequences to improve the speed and accuracy of subsequent unbiased database searches. By deep sequencing, we were able to detect virus sequence in 37% (45/123) of previously negative cases. These included 13 cases with Human Herpesvirus 6 sequences. Other samples contained sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae families. In some cases, the putative viral sequences were virtually identical to known viruses, and in others they diverged, suggesting that they may derive from novel viruses. These results demonstrate the utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness.",2012 Feb 7,"['Yozwiak, Nathan L.', 'Skewes-Cox, Peter', 'Stenglein, Mark D.', 'Balmaseda, Angel', 'Harris, Eva', 'DeRisi, Joseph L.']",PLoS Negl Trop Dis,,,False
e21d9c0b64186b32a1afed5223bfa4e879574cb7,PMC,Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing,http://dx.doi.org/10.1371/journal.pntd.0001485,PMC3274504,22347512,CC BY,"Dengue virus is an emerging infectious agent that infects an estimated 50–100 million people annually worldwide, yet current diagnostic practices cannot detect an etiologic pathogen in ∼40% of dengue-like illnesses. Metagenomic approaches to pathogen detection, such as viral microarrays and deep sequencing, are promising tools to address emerging and non-diagnosable disease challenges. In this study, we used the Virochip microarray and deep sequencing to characterize the spectrum of viruses present in human sera from 123 Nicaraguan patients presenting with dengue-like symptoms but testing negative for dengue virus. We utilized a barcoding strategy to simultaneously deep sequence multiple serum specimens, generating on average over 1 million reads per sample. We then implemented a stepwise bioinformatic filtering pipeline to remove the majority of human and low-quality sequences to improve the speed and accuracy of subsequent unbiased database searches. By deep sequencing, we were able to detect virus sequence in 37% (45/123) of previously negative cases. These included 13 cases with Human Herpesvirus 6 sequences. Other samples contained sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae families. In some cases, the putative viral sequences were virtually identical to known viruses, and in others they diverged, suggesting that they may derive from novel viruses. These results demonstrate the utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness.",2012 Feb 7,"['Yozwiak, Nathan L.', 'Skewes-Cox, Peter', 'Stenglein, Mark D.', 'Balmaseda, Angel', 'Harris, Eva', 'DeRisi, Joseph L.']",PLoS Negl Trop Dis,,,False
3c2f8d1ce0724ee7966c5647836bd996a79c9205,PMC,Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing,http://dx.doi.org/10.1371/journal.pntd.0001485,PMC3274504,22347512,CC BY,"Dengue virus is an emerging infectious agent that infects an estimated 50–100 million people annually worldwide, yet current diagnostic practices cannot detect an etiologic pathogen in ∼40% of dengue-like illnesses. Metagenomic approaches to pathogen detection, such as viral microarrays and deep sequencing, are promising tools to address emerging and non-diagnosable disease challenges. In this study, we used the Virochip microarray and deep sequencing to characterize the spectrum of viruses present in human sera from 123 Nicaraguan patients presenting with dengue-like symptoms but testing negative for dengue virus. We utilized a barcoding strategy to simultaneously deep sequence multiple serum specimens, generating on average over 1 million reads per sample. We then implemented a stepwise bioinformatic filtering pipeline to remove the majority of human and low-quality sequences to improve the speed and accuracy of subsequent unbiased database searches. By deep sequencing, we were able to detect virus sequence in 37% (45/123) of previously negative cases. These included 13 cases with Human Herpesvirus 6 sequences. Other samples contained sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae families. In some cases, the putative viral sequences were virtually identical to known viruses, and in others they diverged, suggesting that they may derive from novel viruses. These results demonstrate the utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness.",2012 Feb 7,"['Yozwiak, Nathan L.', 'Skewes-Cox, Peter', 'Stenglein, Mark D.', 'Balmaseda, Angel', 'Harris, Eva', 'DeRisi, Joseph L.']",PLoS Negl Trop Dis,,,False
400d3287bd63bba9d2a3fe69308c6c1795baebad,PMC,Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing,http://dx.doi.org/10.1371/journal.pntd.0001485,PMC3274504,22347512,CC BY,"Dengue virus is an emerging infectious agent that infects an estimated 50–100 million people annually worldwide, yet current diagnostic practices cannot detect an etiologic pathogen in ∼40% of dengue-like illnesses. Metagenomic approaches to pathogen detection, such as viral microarrays and deep sequencing, are promising tools to address emerging and non-diagnosable disease challenges. In this study, we used the Virochip microarray and deep sequencing to characterize the spectrum of viruses present in human sera from 123 Nicaraguan patients presenting with dengue-like symptoms but testing negative for dengue virus. We utilized a barcoding strategy to simultaneously deep sequence multiple serum specimens, generating on average over 1 million reads per sample. We then implemented a stepwise bioinformatic filtering pipeline to remove the majority of human and low-quality sequences to improve the speed and accuracy of subsequent unbiased database searches. By deep sequencing, we were able to detect virus sequence in 37% (45/123) of previously negative cases. These included 13 cases with Human Herpesvirus 6 sequences. Other samples contained sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae families. In some cases, the putative viral sequences were virtually identical to known viruses, and in others they diverged, suggesting that they may derive from novel viruses. These results demonstrate the utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness.",2012 Feb 7,"['Yozwiak, Nathan L.', 'Skewes-Cox, Peter', 'Stenglein, Mark D.', 'Balmaseda, Angel', 'Harris, Eva', 'DeRisi, Joseph L.']",PLoS Negl Trop Dis,,,False
e1ae1fce6ed744522728aef322c22b5f239b9157,PMC,Effects of a Non-Conservative Sequence on the Properties of β-glucuronidase from Aspergillus terreus Li-20,http://dx.doi.org/10.1371/journal.pone.0030998,PMC3274521,22347419,CC BY,"We cloned the β-glucuronidase gene (AtGUS) from Aspergillus terreus Li-20 encoding 657 amino acids (aa), which can transform glycyrrhizin into glycyrrhetinic acid monoglucuronide (GAMG) and glycyrrhetinic acid (GA). Based on sequence alignment, the C-terminal non-conservative sequence showed low identity with those of other species; thus, the partial sequence AtGUS(-3t) (1–592 aa) was amplified to determine the effects of the non-conservative sequence on the enzymatic properties. AtGUS and AtGUS(-3t) were expressed in E. coli BL21, producing AtGUS-E and AtGUS(-3t)-E, respectively. At the similar optimum temperature (55°C) and pH (AtGUS-E, 6.6; AtGUS(-3t)-E, 7.0) conditions, the thermal stability of AtGUS(-3t)-E was enhanced at 65°C, and the metal ions Co(2+), Ca(2+) and Ni(2+) showed opposite effects on AtGUS-E and AtGUS(-3t)-E, respectively. Furthermore, Km of AtGUS(-3t)-E (1.95 mM) was just nearly one-seventh that of AtGUS-E (12.9 mM), whereas the catalytic efficiency of AtGUS(-3t)-E was 3.2 fold higher than that of AtGUS-E (7.16 vs. 2.24 mM s(−1)), revealing that the truncation of non-conservative sequence can significantly improve the catalytic efficiency of AtGUS. Conformational analysis illustrated significant difference in the secondary structure between AtGUS-E and AtGUS(-3t)-E by circular dichroism (CD). The results showed that the truncation of the non-conservative sequence could preferably alter and influence the stability and catalytic efficiency of enzyme.",2012 Feb 7,"['Liu, Yanli', 'Huangfu, Jie', 'Qi, Feng', 'Kaleem, Imdad', 'E, Wenwen', 'Li, Chun']",PLoS One,,,True
69bce356ec4ad3fcc2a0d7ba9ecfaf0d90d8e423,PMC,Composite Structural Motifs of Binding Sites for Delineating Biological Functions of Proteins,http://dx.doi.org/10.1371/journal.pone.0031437,PMC3275580,22347478,CC BY,"Most biological processes are described as a series of interactions between proteins and other molecules, and interactions are in turn described in terms of atomic structures. To annotate protein functions as sets of interaction states at atomic resolution, and thereby to better understand the relation between protein interactions and biological functions, we conducted exhaustive all-against-all atomic structure comparisons of all known binding sites for ligands including small molecules, proteins and nucleic acids, and identified recurring elementary motifs. By integrating the elementary motifs associated with each subunit, we defined composite motifs that represent context-dependent combinations of elementary motifs. It is demonstrated that function similarity can be better inferred from composite motif similarity compared to the similarity of protein sequences or of individual binding sites. By integrating the composite motifs associated with each protein function, we define meta-composite motifs each of which is regarded as a time-independent diagrammatic representation of a biological process. It is shown that meta-composite motifs provide richer annotations of biological processes than sequence clusters. The present results serve as a basis for bridging atomic structures to higher-order biological phenomena by classification and integration of binding site structures.",2012 Feb 8,"['Kinjo, Akira R.', 'Nakamura, Haruki']",PLoS One,,,True
8ed7e985c1bef92952d4626090ac1c31c9566a23,PMC,"Understanding community perceptions, social norms and current practice related to respiratory infection in Bangladesh during 2009: a qualitative formative study",http://dx.doi.org/10.1186/1471-2458-11-901,PMC3276487,22136080,CC BY,"BACKGROUND: Respiratory infections are the leading cause of childhood deaths in Bangladesh. Promoting respiratory hygiene may reduce infection transmission. This formative research explored community perceptions about respiratory infections. METHODS: We conducted 34 in-depth interviews and 16 focus group discussions with community members and school children to explore respiratory hygiene related perceptions, practices, and social norms in an urban and a rural setting. We conducted unstructured observations on respiratory hygiene practices in public markets. RESULTS: Informants were not familiar with the term ""respiratory infection""; most named diseases that had no relation to respiratory dysfunction. Informants reported that their community identified a number of 'good behaviors' related to respiratory hygiene, but they also noted, and we observed, that very few people practiced these. All informants cited hot/cold weather changes or using cold water as causes for catching cold. They associated transmission of respiratory infections with close contact with a sick person's breath, cough droplets, or spit; sharing a sick person's utensils and food. Informants suggested that avoiding such contact was the most effective method to prevent respiratory infection. Although informants perceived that handwashing after coughing or sneezing might prevent illness, they felt this was not typically feasible or practical. CONCLUSION: Community perceptions of respiratory infections include both concerns with imbalances between hot and cold, and with person-to-person transmission. Many people were aware of measures that could prevent respiratory infection, but did not practice them. Interventions that leverage community understanding of person-to-person transmission and that encourage the practice of their identified 'good behaviors' related to respiratory hygiene may reduce respiratory disease transmission.",2011 Dec 4,"['Nizame, Fosiul A', 'Nasreen, Sharifa', 'Unicomb, Leanne', 'Southern, Dorothy', 'Gurley, Emily S', 'Arman, Shaila', 'Kadir, Mohammad A', 'Azziz-Baumgartner, Eduardo', 'Luby, Stephen P', 'Winch, Peter J']",BMC Public Health,,,True
09403dce0f0c10723150a14e1ea2f00b11dc05fb,PMC,Evaluation of a Web-Based Intervention to Promote Hand Hygiene: Exploratory Randomized Controlled Trial,http://dx.doi.org/10.2196/jmir.1963,PMC3278093,22155673,CC BY,"BACKGROUND: Hand-washing is regarded as a potentially important behavior for preventing transmission of respiratory infection, particularly during a pandemic. OBJECTIVE: The objective of our study was to evaluate whether a Web-based intervention can encourage more frequent hand-washing in the home, and to examine potential mediators and moderators of outcomes, as a necessary first step before testing effects of the intervention on infection rates in the PRIMIT trial (PRimary care trial of a website based Infection control intervention to Modify Influenza-like illness and respiratory infection Transmission). METHODS: In a parallel-group pragmatic exploratory trial design, 517 nonblinded adults recruited through primary care were automatically randomly assigned to a fully automated intervention comprising 4 sessions of tailored motivational messages and self-regulation support (n = 324) or to a no-intervention control group (n = 179; ratio 2:1). Hand-washing frequency and theory of planned behavior cognitions relating to hand-washing were assessed by online questionnaires at baseline (in only half of the control participants, to permit evaluation of effects of baseline assessment on effect sizes), at 4 weeks (postintervention; all participants), and at 12 weeks. RESULTS: Hand-washing rates in the intervention group were higher at 4 weeks than in the control group (mean 4.40, n = 285 and mean 4.04, n = 157, respectively; P < .001, Cohen d = 0.42) and remained higher at 12 weeks (mean 4.45, n = 282 and mean 4.12, n = 154, respectively; P < .001, Cohen d = 0.34). Hand-washing intentions and positive attitudes toward hand-washing increased more from baseline to 4 weeks in the intervention group than in the control group. Mediation analyses revealed positive indirect effects of the intervention on change in hand-washing via intentions (coefficient = .15, 95% confidence interval [CI], .08–.26) and attitudes (coefficient = 0.16, 95% CI, .09–.26). Moderator analyses confirmed that the intervention was similarly effective for men and women, those of higher and lower socioeconomic status, and those with higher and lower levels of perceived risk. CONCLUSIONS: This study provides promising evidence that Web-based interventions could potentially provide an effective method of promoting hand hygiene in the home. Data were collected during the 2010 influenza pandemic, when participants in both groups had already been exposed to extensive publicity about the need for hand hygiene, suggesting that our intervention could add to existing public health campaigns. However, further research is required to determine the effects of the intervention on actual infection rates. TRIAL: International Standard Randomized Controlled Trial Number (ISRCTN): 75058295; http://www.controlled-trials.com/ISRCTN75058295 (Archived by WebCite at http://www.webcitation.org/62KSbkNmm)",2011 Dec 9,"['Yardley, Lucy', 'Miller, Sascha', 'Schlotz, Wolff', 'Little, Paul']",J Med Internet Res,,,True
6feb6f6d40f0c7540336a923c65c53a88afad147,PMC,Evaluation of a Web-Based Intervention to Promote Hand Hygiene: Exploratory Randomized Controlled Trial,http://dx.doi.org/10.2196/jmir.1963,PMC3278093,22155673,CC BY,"BACKGROUND: Hand-washing is regarded as a potentially important behavior for preventing transmission of respiratory infection, particularly during a pandemic. OBJECTIVE: The objective of our study was to evaluate whether a Web-based intervention can encourage more frequent hand-washing in the home, and to examine potential mediators and moderators of outcomes, as a necessary first step before testing effects of the intervention on infection rates in the PRIMIT trial (PRimary care trial of a website based Infection control intervention to Modify Influenza-like illness and respiratory infection Transmission). METHODS: In a parallel-group pragmatic exploratory trial design, 517 nonblinded adults recruited through primary care were automatically randomly assigned to a fully automated intervention comprising 4 sessions of tailored motivational messages and self-regulation support (n = 324) or to a no-intervention control group (n = 179; ratio 2:1). Hand-washing frequency and theory of planned behavior cognitions relating to hand-washing were assessed by online questionnaires at baseline (in only half of the control participants, to permit evaluation of effects of baseline assessment on effect sizes), at 4 weeks (postintervention; all participants), and at 12 weeks. RESULTS: Hand-washing rates in the intervention group were higher at 4 weeks than in the control group (mean 4.40, n = 285 and mean 4.04, n = 157, respectively; P < .001, Cohen d = 0.42) and remained higher at 12 weeks (mean 4.45, n = 282 and mean 4.12, n = 154, respectively; P < .001, Cohen d = 0.34). Hand-washing intentions and positive attitudes toward hand-washing increased more from baseline to 4 weeks in the intervention group than in the control group. Mediation analyses revealed positive indirect effects of the intervention on change in hand-washing via intentions (coefficient = .15, 95% confidence interval [CI], .08–.26) and attitudes (coefficient = 0.16, 95% CI, .09–.26). Moderator analyses confirmed that the intervention was similarly effective for men and women, those of higher and lower socioeconomic status, and those with higher and lower levels of perceived risk. CONCLUSIONS: This study provides promising evidence that Web-based interventions could potentially provide an effective method of promoting hand hygiene in the home. Data were collected during the 2010 influenza pandemic, when participants in both groups had already been exposed to extensive publicity about the need for hand hygiene, suggesting that our intervention could add to existing public health campaigns. However, further research is required to determine the effects of the intervention on actual infection rates. TRIAL: International Standard Randomized Controlled Trial Number (ISRCTN): 75058295; http://www.controlled-trials.com/ISRCTN75058295 (Archived by WebCite at http://www.webcitation.org/62KSbkNmm)",2011 Dec 9,"['Yardley, Lucy', 'Miller, Sascha', 'Schlotz, Wolff', 'Little, Paul']",J Med Internet Res,,,False
1575931c6fe7aea67ea3ced0ebe1df4d2604864c,PMC,Evaluation of a Web-Based Intervention to Promote Hand Hygiene: Exploratory Randomized Controlled Trial,http://dx.doi.org/10.2196/jmir.1963,PMC3278093,22155673,CC BY,"BACKGROUND: Hand-washing is regarded as a potentially important behavior for preventing transmission of respiratory infection, particularly during a pandemic. OBJECTIVE: The objective of our study was to evaluate whether a Web-based intervention can encourage more frequent hand-washing in the home, and to examine potential mediators and moderators of outcomes, as a necessary first step before testing effects of the intervention on infection rates in the PRIMIT trial (PRimary care trial of a website based Infection control intervention to Modify Influenza-like illness and respiratory infection Transmission). METHODS: In a parallel-group pragmatic exploratory trial design, 517 nonblinded adults recruited through primary care were automatically randomly assigned to a fully automated intervention comprising 4 sessions of tailored motivational messages and self-regulation support (n = 324) or to a no-intervention control group (n = 179; ratio 2:1). Hand-washing frequency and theory of planned behavior cognitions relating to hand-washing were assessed by online questionnaires at baseline (in only half of the control participants, to permit evaluation of effects of baseline assessment on effect sizes), at 4 weeks (postintervention; all participants), and at 12 weeks. RESULTS: Hand-washing rates in the intervention group were higher at 4 weeks than in the control group (mean 4.40, n = 285 and mean 4.04, n = 157, respectively; P < .001, Cohen d = 0.42) and remained higher at 12 weeks (mean 4.45, n = 282 and mean 4.12, n = 154, respectively; P < .001, Cohen d = 0.34). Hand-washing intentions and positive attitudes toward hand-washing increased more from baseline to 4 weeks in the intervention group than in the control group. Mediation analyses revealed positive indirect effects of the intervention on change in hand-washing via intentions (coefficient = .15, 95% confidence interval [CI], .08–.26) and attitudes (coefficient = 0.16, 95% CI, .09–.26). Moderator analyses confirmed that the intervention was similarly effective for men and women, those of higher and lower socioeconomic status, and those with higher and lower levels of perceived risk. CONCLUSIONS: This study provides promising evidence that Web-based interventions could potentially provide an effective method of promoting hand hygiene in the home. Data were collected during the 2010 influenza pandemic, when participants in both groups had already been exposed to extensive publicity about the need for hand hygiene, suggesting that our intervention could add to existing public health campaigns. However, further research is required to determine the effects of the intervention on actual infection rates. TRIAL: International Standard Randomized Controlled Trial Number (ISRCTN): 75058295; http://www.controlled-trials.com/ISRCTN75058295 (Archived by WebCite at http://www.webcitation.org/62KSbkNmm)",2011 Dec 9,"['Yardley, Lucy', 'Miller, Sascha', 'Schlotz, Wolff', 'Little, Paul']",J Med Internet Res,,,True
df7ce7b791dbb8848b6222b823622cc5866f681e,PMC,Variability in transmissibility of the 2009 H1N1 pandemic in Canadian communities,http://dx.doi.org/10.1186/1756-0500-4-537,PMC3278401,22166307,CC BY,"BACKGROUND: The prevalence and severity of the 2009 H1N1 pandemic appeared to vary significantly across populations and geographic regions. We sought to investigate the variability in transmissibility of H1N1 pandemic in different health regions (including urban centres and remote, isolated communities) in the province of Manitoba, Canada. METHODS: The Richards model was used to fit to the daily number of laboratory-confirmed cases and estimate transmissibility (referred to as the basic reproduction number, R(0)), doubling times, and turning points of outbreaks in both spring and fall waves of the H1N1 pandemic in several health regions. RESULTS: We observed considerable variation in R(0 )estimates ranging from 1.55 to 2.24, with confidence intervals ranging from 1.45 to 2.88, for an average generation time of 2.9 days, and shorter doubling times in some remote and isolated communities compared to urban centres, suggesting a more rapid spread of disease in these communities during the first wave. For the second wave, R(e), the effective reproduction number, is estimated to be lower for remote and isolated communities; however, outbreaks appear to have been driven by somewhat higher transmissibility in urban centres. CONCLUSIONS: There was considerable geographic variation in transmissibility of the 2009 pandemic outbreaks. While highlighting the importance of estimating R(0 )for informing health responses, the findings indicate that projecting the transmissibility for large-scale epidemics may not faithfully characterize the early spread of disease in remote and isolated communities.",2011 Dec 13,"['Mostaço-Guidolin, Luiz C', 'Greer, Amy', 'Sander, Beate', 'Wu, Jianhong', 'Moghadas, Seyed M']",BMC Res Notes,,,True
35fa07c7c7d1803f22859f6647d5d743e7ad7652,PMC,In silico approach to screen compounds active against parasitic nematodes of major socio-economic importance,http://dx.doi.org/10.1186/1471-2105-12-S13-S25,PMC3278842,22373185,CC BY,"BACKGROUND: Infections due to parasitic nematodes are common causes of morbidity and fatality around the world especially in developing nations. At present however, there are only three major classes of drugs for treating human nematode infections. Additionally the scientific knowledge on the mechanism of action and the reason for the resistance to these drugs is poorly understood. Commercial incentives to design drugs that are endemic to developing countries are limited therefore, virtual screening in academic settings can play a vital role is discovering novel drugs useful against neglected diseases. In this study we propose to build robust machine learning model to classify and screen compounds active against parasitic nematodes. RESULTS: A set of compounds active against parasitic nematodes were collated from various literature sources including PubChem while the inactive set was derived from DrugBank database. The support vector machine (SVM) algorithm was used for model development, and stratified ten-fold cross validation was used to evaluate the performance of each classifier. The best results were obtained using the radial basis function kernel. The SVM method achieved an accuracy of 81.79% on an independent test set. Using the model developed above, we were able to indentify novel compounds with potential anthelmintic activity. CONCLUSION: In this study, we successfully present the SVM approach for predicting compounds active against parasitic nematodes which suggests the effectiveness of computational approaches for antiparasitic drug discovery. Although, the accuracy obtained is lower than the previously reported in a similar study but we believe that our model is more robust because we intentionally employed stringent criteria to select inactive dataset thus making it difficult for the model to classify compounds. The method presents an alternative approach to the existing traditional methods and may be useful for predicting hitherto novel anthelmintic compounds.",2011 Nov 30,"['Khanna, Varun', 'Ranganathan, Shoba']",BMC Bioinformatics,,,True
2f8c155ac0b65122bf485baf2bd6c2fe78e21373,PMC,"Characterization of the Viral Microbiome in Patients with Severe Lower Respiratory Tract Infections, Using Metagenomic Sequencing",http://dx.doi.org/10.1371/journal.pone.0030875,PMC3280267,22355331,CC BY,"The human respiratory tract is heavily exposed to microorganisms. Viral respiratory tract pathogens, like RSV, influenza and rhinoviruses cause major morbidity and mortality from respiratory tract disease. Furthermore, as viruses have limited means of transmission, viruses that cause pathogenicity in other tissues may be transmitted through the respiratory tract. It is therefore important to chart the human virome in this compartment. We have studied nasopharyngeal aspirate samples submitted to the Karolinska University Laboratory, Stockholm, Sweden from March 2004 to May 2005 for diagnosis of respiratory tract infections. We have used a metagenomic sequencing strategy to characterize viruses, as this provides the most unbiased view of the samples. Virus enrichment followed by 454 sequencing resulted in totally 703,790 reads and 110,931 of these were found to be of viral origin by using an automated classification pipeline. The snapshot of the respiratory tract virome of these 210 patients revealed 39 species and many more strains of viruses. Most of the viral sequences were classified into one of three major families; Paramyxoviridae, Picornaviridae or Orthomyxoviridae. The study also identified one novel type of Rhinovirus C, and identified a number of previously undescribed viral genetic fragments of unknown origin.",2012 Feb 15,"['Lysholm, Fredrik', 'Wetterbom, Anna', 'Lindau, Cecilia', 'Darban, Hamid', 'Bjerkner, Annelie', 'Fahlander, Kristina', 'Lindberg, A. Michael', 'Persson, Bengt', 'Allander, Tobias', 'Andersson, Björn']",PLoS One,,,True
24b20768feb528be2a620b4afcd761cdfabcb183,PMC,The Human Antibody Response to Dengue Virus Infection,http://dx.doi.org/10.3390/v3122374,PMC3280510,22355444,CC BY,"Dengue viruses (DENV) are the causative agents of dengue fever (DF) and dengue hemorrhagic fever (DHF). Here we review the current state of knowledge about the human antibody response to dengue and identify important knowledge gaps. A large body of work has demonstrated that antibodies can neutralize or enhance DENV infection. Investigators have mainly used mouse monoclonal antibodies (MAbs) to study interactions between DENV and antibodies. These studies indicate that antibody neutralization of DENVs is a “multi-hit” phenomenon that requires the binding of multiple antibodies to neutralize a virion. The most potently neutralizing mouse MAbs bind to surface exposed epitopes on domain III of the dengue envelope (E) protein. One challenge facing the dengue field now is to extend these studies with mouse MAbs to better understand the human antibody response. The human antibody response is complex as it involves a polyclonal response to primary and secondary infections with 4 different DENV serotypes. Here we review studies conducted with immune sera and MAbs isolated from people exposed to dengue infections. Most dengue-specific antibodies in human immune sera are weakly neutralizing and bind to multiple DENV serotypes. The human antibodies that potently and type specifically neutralize DENV represent a small fraction of the total DENV-specific antibody response. Moreover, these neutralizing antibodies appear to bind to novel epitopes including complex, quaternary epitopes that are only preserved on the intact virion. These studies establish that human and mouse antibodies recognize distinct epitopes on the dengue virion. The leading theory proposed to explain the increased risk of severe disease in secondary cases is antibody dependent enhancement (ADE), which postulates that weakly neutralizing antibodies from the first infection bind to the second serotype and enhance infection of FcγR bearing myeloid cells such as monocytes and macrophages. Here we review results from human, animal and cell culture studies relevant to the ADE hypothesis. By understanding how human antibodies neutralize or enhance DENV, it will be possible to better evaluate existing vaccines and develop the next generation of novel vaccines.",2011 Nov 25,"['Wahala, Wahala M. P. B.', 'de Silva, Aravinda M.']",Viruses,,,True
0e82e56decffd22f29d8229da88e38840404ae37,PMC,Replication-Competent Recombinant Porcine Reproductive and Respiratory Syndrome (PRRS) Viruses Expressing Indicator Proteins and Antiviral Cytokines,http://dx.doi.org/10.3390/v4010102,PMC3280517,22355454,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) can subvert early innate immunity, which leads to ineffective antimicrobial responses. Overcoming immune subversion is critical for developing vaccines and other measures to control this devastating swine virus. The overall goal of this work was to enhance innate and adaptive immunity following vaccination through the expression of interferon (IFN) genes by the PRRSV genome. We have constructed a series of recombinant PRRS viruses using an infectious PRRSV cDNA clone (pCMV-P129). Coding regions of exogenous genes, which included Renilla luciferase (Rluc), green and red fluorescent proteins (GFP and DsRed, respectively) and several interferons (IFNs), were constructed and expressed through a unique subgenomic mRNA placed between ORF1b and ORF2 of the PRRSV infectious clone. The constructs, which expressed Rluc, GFP, DsRed, efficiently produced progeny viruses and mimicked the parental virus in both MARC-145 cells and porcine macrophages. In contrast, replication of IFN-expressing viruses was attenuated, similar to the level of replication observed after the addition of exogenous IFN. Furthermore, the IFN expressing viruses inhibited the replication of a second PRRS virus co-transfected or co-infected. Inhibition by the different IFN subtypes corresponded to their anti-PRRSV activity, i.e., IFNω5 ° IFNα1 > IFN-β > IFNδ3. In summary, the indicator-expressing viruses provided an efficient means for real-time monitoring of viral replication thus allowing high‑throughput elucidation of the role of host factors in PRRSV infection. This was shown when they were used to clearly demonstrate the involvement of tumor susceptibility gene 101 (TSG101) in the early stage of PRRSV infection. In addition, replication‑competent IFN-expressing viruses may be good candidates for development of modified live virus (MLV) vaccines, which are capable of reversing subverted innate immune responses and may induce more effective adaptive immunity against PRRSV infection.",2012 Jan 18,"['Sang, Yongming', 'Shi, Jishu', 'Sang, Wenjing', 'Rowland, Raymond R. R.', 'Blecha, Frank']",Viruses,,,True
30589bfb622ec85458e9bde716261ca00f8b342d,PMC,Replication-Competent Recombinant Porcine Reproductive and Respiratory Syndrome (PRRS) Viruses Expressing Indicator Proteins and Antiviral Cytokines,http://dx.doi.org/10.3390/v4010102,PMC3280517,22355454,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) can subvert early innate immunity, which leads to ineffective antimicrobial responses. Overcoming immune subversion is critical for developing vaccines and other measures to control this devastating swine virus. The overall goal of this work was to enhance innate and adaptive immunity following vaccination through the expression of interferon (IFN) genes by the PRRSV genome. We have constructed a series of recombinant PRRS viruses using an infectious PRRSV cDNA clone (pCMV-P129). Coding regions of exogenous genes, which included Renilla luciferase (Rluc), green and red fluorescent proteins (GFP and DsRed, respectively) and several interferons (IFNs), were constructed and expressed through a unique subgenomic mRNA placed between ORF1b and ORF2 of the PRRSV infectious clone. The constructs, which expressed Rluc, GFP, DsRed, efficiently produced progeny viruses and mimicked the parental virus in both MARC-145 cells and porcine macrophages. In contrast, replication of IFN-expressing viruses was attenuated, similar to the level of replication observed after the addition of exogenous IFN. Furthermore, the IFN expressing viruses inhibited the replication of a second PRRS virus co-transfected or co-infected. Inhibition by the different IFN subtypes corresponded to their anti-PRRSV activity, i.e., IFNω5 ° IFNα1 > IFN-β > IFNδ3. In summary, the indicator-expressing viruses provided an efficient means for real-time monitoring of viral replication thus allowing high‑throughput elucidation of the role of host factors in PRRSV infection. This was shown when they were used to clearly demonstrate the involvement of tumor susceptibility gene 101 (TSG101) in the early stage of PRRSV infection. In addition, replication‑competent IFN-expressing viruses may be good candidates for development of modified live virus (MLV) vaccines, which are capable of reversing subverted innate immune responses and may induce more effective adaptive immunity against PRRSV infection.",2012 Jan 18,"['Sang, Yongming', 'Shi, Jishu', 'Sang, Wenjing', 'Rowland, Raymond R. R.', 'Blecha, Frank']",Viruses,,,False
412833ef524797198177f582425f82e45c0f7a06,PMC,A Co-Opted DEAD-Box RNA Helicase Enhances Tombusvirus Plus-Strand Synthesis,http://dx.doi.org/10.1371/journal.ppat.1002537,PMC3280988,22359508,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. In this paper, we show that an essential translation factor, Ded1p DEAD-box RNA helicase of yeast, directly affects replication of Tomato bushy stunt virus (TBSV). To separate the role of Ded1p in viral protein translation from its putative replication function, we utilized a cell-free TBSV replication assay and recombinant Ded1p. The in vitro data show that Ded1p plays a role in enhancing plus-strand synthesis by the viral replicase. We also find that Ded1p is a component of the tombusvirus replicase complex and Ded1p binds to the 3′-end of the viral minus-stranded RNA. The data obtained with wt and ATPase deficient Ded1p mutants support the model that Ded1p unwinds local structures at the 3′-end of the TBSV (−)RNA, rendering the RNA compatible for initiation of (+)-strand synthesis. Interestingly, we find that Ded1p and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is another host factor for TBSV, play non-overlapping functions to enhance (+)-strand synthesis. Altogether, the two host factors enhance TBSV replication synergistically by interacting with the viral (−)RNA and the replication proteins. In addition, we have developed an in vitro assay for Flock house virus (FHV), a small RNA virus of insects, that also demonstrated positive effect on FHV replicase activity by the added Ded1p helicase. Thus, two small RNA viruses, which do not code for their own helicases, seems to recruit a host RNA helicase to aid their replication in infected cells.",2012 Feb 16,"['Kovalev, Nikolay', 'Pogany, Judit', 'Nagy, Peter D.']",PLoS Pathog,,,True
4a07858e23c845b36af362b5dc31af7993fbca56,PMC,A Co-Opted DEAD-Box RNA Helicase Enhances Tombusvirus Plus-Strand Synthesis,http://dx.doi.org/10.1371/journal.ppat.1002537,PMC3280988,22359508,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. In this paper, we show that an essential translation factor, Ded1p DEAD-box RNA helicase of yeast, directly affects replication of Tomato bushy stunt virus (TBSV). To separate the role of Ded1p in viral protein translation from its putative replication function, we utilized a cell-free TBSV replication assay and recombinant Ded1p. The in vitro data show that Ded1p plays a role in enhancing plus-strand synthesis by the viral replicase. We also find that Ded1p is a component of the tombusvirus replicase complex and Ded1p binds to the 3′-end of the viral minus-stranded RNA. The data obtained with wt and ATPase deficient Ded1p mutants support the model that Ded1p unwinds local structures at the 3′-end of the TBSV (−)RNA, rendering the RNA compatible for initiation of (+)-strand synthesis. Interestingly, we find that Ded1p and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is another host factor for TBSV, play non-overlapping functions to enhance (+)-strand synthesis. Altogether, the two host factors enhance TBSV replication synergistically by interacting with the viral (−)RNA and the replication proteins. In addition, we have developed an in vitro assay for Flock house virus (FHV), a small RNA virus of insects, that also demonstrated positive effect on FHV replicase activity by the added Ded1p helicase. Thus, two small RNA viruses, which do not code for their own helicases, seems to recruit a host RNA helicase to aid their replication in infected cells.",2012 Feb 16,"['Kovalev, Nikolay', 'Pogany, Judit', 'Nagy, Peter D.']",PLoS Pathog,,,False
1868242435edf92a6b0018f2569c2012f672ddf7,PMC,Hemagglutinin from the H5N1 Virus Activates Janus Kinase 3 to Dysregulate Innate Immunity,http://dx.doi.org/10.1371/journal.pone.0031721,PMC3280993,22359619,CC BY,"Highly pathogenic avian influenza viruses (HPAIVs) cause severe disease in humans. There are no effective vaccines or antiviral therapies currently available to control fatal outbreaks due in part to the lack of understanding of virus-mediated immunopathology. In our study, we used hemagglutinin (HA) of H5N1 virus to investigate the related signaling pathways and their relationship to dysregulated innate immune reaction. We found the HA of H5N1 avian influenza triggered an abnormal innate immune signalling in the pulmonary epithelial cells, through an unusual process involving activation of Janus kinase 3 (JAK3) that is exclusively associated with γc chain and is essential for signaling via all γc cytokine receptors. By using a selective JAK3 inhibitor and JAK3 knockout mice, we have, for the first time, demonstrated the ability to target active JAK3 to counteract injury to the lungs and protect immunocytes from acute hypercytokinemia -induced destruction following the challenge of H5N1 HA in vitro and in vivo. On the basis of the present data, it appears that the efficacy of selective JAK3 inhibition is likely based on its ability to block multiple cytokines and protect against a superinflammatory response to pathogen-associated molecular patterns (PAMPs) attack. Our findings highlight the potential value of selective JAK3 inhibitor in treating the fatal immunopathology caused by H5N1 challenge.",2012 Feb 16,"['Xu, Wei', 'Chen, Minhui', 'Ge, Nanhai', 'Xu, Jun']",PLoS One,,,True
98086d212b4a5249cfc45f05953fd0abf43891d9,PMC,Trends in Notifiable Infectious Diseases in China: Implications for Surveillance and Population Health Policy,http://dx.doi.org/10.1371/journal.pone.0031076,PMC3281048,22359565,CC BY,"This study aimed to analyse trends in notifiable infectious diseases in China, in their historical context. Both English and Chinese literature was searched and diseases were categorised according to the type of disease or transmission route. Temporal trends of morbidity and mortality rates were calculated for eight major infectious diseases types. Strong government commitment to public health responses and improvements in quality of life has led to the eradication or containment of a wide range of infectious diseases in China. The overall infectious diseases burden experienced a dramatic drop during 1975–1995, but since then, it reverted and maintained a gradual upward trend to date. Most notifiable diseases are contained at a low endemic level; however, local small-scale outbreaks remain common. Tuberculosis, as a bacterial infection, has re-emerged since the 1990s and has become prevalent in the country. Sexually transmitted infections are in a rapid, exponential growth phase, spreading from core groups to the general population. Together human immunodeficiency virus (HIV), they account for 39% of all death cases due to infectious diseases in China in 2008. Zoonotic infections, such as severe acute respiratory syndrome (SARS), rabies and influenza, pose constant threats to Chinese residents and remain the most deadly disease type among the infected individuals. Therefore, second-generation surveillance of behavioural risks or vectors associated with pathogen transmission should be scaled up. It is necessary to implement public health interventions that target HIV and relevant coinfections, address transmission associated with highly mobile populations, and reduce the risk of cross-species transmission of zoonotic pathogens.",2012 Feb 16,"['Zhang, Lei', 'Wilson, David P.']",PLoS One,,,True
e725656b0cdd0f7e78279187e0c251cf8683f1e5,PMC,Removal of Hepatitis C Virus-Infected Cells by a Zymogenized Bacterial Toxin,http://dx.doi.org/10.1371/journal.pone.0032320,PMC3281143,22359682,CC BY,"Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and has become a global health threat. No HCV vaccine is currently available and treatment with antiviral therapy is associated with adverse side effects. Moreover, there is no preventive therapy for recurrent hepatitis C post liver transplantation. The NS3 serine protease is necessary for HCV replication and represents a prime target for developing anti HCV therapies. Recently we described a therapeutic approach for eradication of HCV infected cells that is based on protein delivery of two NS3 protease-activatable recombinant toxins we named “zymoxins”. These toxins were inactivated by fusion to rationally designed inhibitory peptides via NS3-cleavable linkers. Once delivered to cells where NS3 protease is present, the inhibitory peptide is removed resulting in re-activation of cytotoxic activity. The zymoxins we described suffered from two limitations: they required high levels of protease for activation and had basal activities in the un-activated form that resulted in a narrow potential therapeutic window. Here, we present a solution that overcame the major limitations of the “first generation zymoxins” by converting MazF ribonuclease, the toxic component of the E. coli chromosomal MazEF toxin-antitoxin system, into an NS3-activated zymoxin that is introduced to cells by means of gene delivery. We constructed an expression cassette that encodes for a single polypeptide that incorporates both the toxin and a fragment of its potent natural antidote, MazE, linked via an NS3-cleavable linker. While covalently paired to its inhibitor, the ribonuclease is well tolerated when expressed in naïve, healthy cells. In contrast, activating proteolysis that is induced by even low levels of NS3, results in an eradication of NS3 expressing model cells and HCV infected cells. Zymoxins may thus become a valuable tool in eradicating cells infected by intracellular pathogens that express intracellular proteases.",2012 Feb 16,"['Shapira, Assaf', 'Shapira, Shiran', 'Gal-Tanamy, Meital', 'Zemel, Romy', 'Tur-Kaspa, Ran', 'Benhar, Itai']",PLoS One,,,True
5b87c5054e29782b51940d6ab29ce3ca2b27d54b,PMC,Transmission of Infectious Diseases En Route to Habitat Hotspots,http://dx.doi.org/10.1371/journal.pone.0031290,PMC3282722,22363606,CC BY,"BACKGROUND: The spread of infectious diseases in wildlife populations is influenced by patterns of between-host contacts. Habitat “hotspots” - places attracting a large numbers of individuals or social groups - can significantly alter contact patterns and, hence, disease propagation. Research on the importance of habitat hotspots in wildlife epidemiology has primarily focused on how inter-individual contacts occurring at the hotspot itself increase disease transmission. However, in territorial animals, epidemiologically important contacts may primarily occur as animals cross through territories of conspecifics en route to habitat hotspots. So far, the phenomenon has received little attention. Here, we investigate the importance of these contacts in the case where infectious individuals keep visiting the hotspots and in the case where these individuals are not able to travel to the hotspot any more. METHODOLOGY AND PRINCIPAL FINDINGS: We developed a simulation epidemiological model to investigate both cases in a scenario when transmission at the hotspot does not occur. We find that (i) hotspots still exacerbate epidemics, (ii) when infectious individuals do not travel to the hotspot, the most vulnerable individuals are those residing at intermediate distances from the hotspot rather than nearby, and (iii) the epidemiological vulnerability of a population is the highest when the number of hotspots is intermediate. CONCLUSIONS AND SIGNIFICANCE: By altering animal movements in their vicinity, habitat hotspots can thus strongly increase the spread of infectious diseases, even when disease transmission does not occur at the hotspot itself. Interestingly, when animals only visit the nearest hotspot, creating additional artificial hotspots, rather than reducing their number, may be an efficient disease control measure.",2012 Feb 20,"['Benavides, Julio', 'Walsh, Peter D.', 'Meyers, Lauren Ancel', 'Raymond, Michel', 'Caillaud, Damien']",PLoS One,,,True
7e889eb3dc54b352c2689b84be7a52f121f80b56,PMC,The Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human Members,http://dx.doi.org/10.1371/journal.pone.0031961,PMC3282796,22363774,CC BY,"The Interferon induced transmembrane proteins (IFITM) are a family of transmembrane proteins that is known to inhibit cell invasion of viruses such as HIV-1 and influenza. We show that the IFITM genes are a subfamily in a larger family of transmembrane (TM) proteins that we call Dispanins, which refers to a common 2TM structure. We mined the Dispanins in 36 eukaryotic species, covering all major eukaryotic groups, and investigated their evolutionary history using Bayesian and maximum likelihood approaches to infer a phylogenetic tree. We identified ten human genes that together with the known IFITM genes form the Dispanin family. We show that the Dispanins first emerged in eukaryotes in a common ancestor of choanoflagellates and metazoa, and that the family later expanded in vertebrates where it forms four subfamilies (A–D). Interestingly, we also find that the family is found in several different phyla of bacteria and propose that it was horizontally transferred to eukaryotes from bacteria in the common ancestor of choanoflagellates and metazoa. The bacterial and eukaryotic sequences have a considerably conserved protein structure. In conclusion, we introduce a novel family, the Dispanins, together with a nomenclature based on the evolutionary origin.",2012 Feb 20,"['Sällman Almén, Markus', 'Bringeland, Nathalie', 'Fredriksson, Robert', 'Schiöth, Helgi B.']",PLoS One,,,True
4e9f9684ec67208f02fa5b822b18ccfa79ca6b6b,PMC,"First Human Rabies Case in French Guiana, 2008: Epidemiological Investigation and Control",http://dx.doi.org/10.1371/journal.pntd.0001537,PMC3283561,22363830,CC BY,"BACKGROUND: Until 2008, human rabies had never been reported in French Guiana. On 28 May 2008, the French National Reference Center for Rabies (Institut Pasteur, Paris) confirmed the rabies diagnosis, based on hemi-nested polymerase chain reaction on skin biopsy and saliva specimens from a Guianan, who had never travelled overseas and died in Cayenne after presenting clinically typical meningoencephalitis. METHODOLOGY/PRINCIPAL FINDINGS: Molecular typing of the virus identified a Lyssavirus (Rabies virus species), closely related to those circulating in hematophagous bats (mainly Desmodus rotundus) in Latin America. A multidisciplinary Crisis Unit was activated. Its objectives were to implement an epidemiological investigation and a veterinary survey, to provide control measures and establish a communications program. The origin of the contamination was not formally established, but was probably linked to a bat bite based on the virus type isolated. After confirming exposure of 90 persons, they were vaccinated against rabies: 42 from the case's entourage and 48 healthcare workers. To handle that emergence and the local population's increased demand to be vaccinated, a specific communications program was established using several media: television, newspaper, radio. CONCLUSION/SIGNIFICANCE: This episode, occurring in the context of a Department far from continental France, strongly affected the local population, healthcare workers and authorities, and the management team faced intense pressure. This observation confirms that the risk of contracting rabies in French Guiana is real, with consequences for population educational program, control measures, medical diagnosis and post-exposure prophylaxis.",2012 Feb 21,"['Meynard, Jean-Baptiste', 'Flamand, Claude', 'Dupuy, Céline', 'Mahamat, Aba', 'Eltges, Françoise', 'Queuche, Frederic', 'Renner, Julien', 'Fontanella, Jean-Michel', 'Hommel, Didier', 'Dussart, Philippe', 'Grangier, Claire', 'Djossou, Félix', 'Dacheux, Laurent', 'Goudal, Maryvonne', 'Berger, Franck', 'Ardillon, Vanessa', 'Krieger, Nicolas', 'Bourhy, Hervé', 'Spiegel, André']",PLoS Negl Trop Dis,,,True
889d6b9282d6ee49c9bdde84352fe9c251e6aae5,PMC,"First Human Rabies Case in French Guiana, 2008: Epidemiological Investigation and Control",http://dx.doi.org/10.1371/journal.pntd.0001537,PMC3283561,22363830,CC BY,"BACKGROUND: Until 2008, human rabies had never been reported in French Guiana. On 28 May 2008, the French National Reference Center for Rabies (Institut Pasteur, Paris) confirmed the rabies diagnosis, based on hemi-nested polymerase chain reaction on skin biopsy and saliva specimens from a Guianan, who had never travelled overseas and died in Cayenne after presenting clinically typical meningoencephalitis. METHODOLOGY/PRINCIPAL FINDINGS: Molecular typing of the virus identified a Lyssavirus (Rabies virus species), closely related to those circulating in hematophagous bats (mainly Desmodus rotundus) in Latin America. A multidisciplinary Crisis Unit was activated. Its objectives were to implement an epidemiological investigation and a veterinary survey, to provide control measures and establish a communications program. The origin of the contamination was not formally established, but was probably linked to a bat bite based on the virus type isolated. After confirming exposure of 90 persons, they were vaccinated against rabies: 42 from the case's entourage and 48 healthcare workers. To handle that emergence and the local population's increased demand to be vaccinated, a specific communications program was established using several media: television, newspaper, radio. CONCLUSION/SIGNIFICANCE: This episode, occurring in the context of a Department far from continental France, strongly affected the local population, healthcare workers and authorities, and the management team faced intense pressure. This observation confirms that the risk of contracting rabies in French Guiana is real, with consequences for population educational program, control measures, medical diagnosis and post-exposure prophylaxis.",2012 Feb 21,"['Meynard, Jean-Baptiste', 'Flamand, Claude', 'Dupuy, Céline', 'Mahamat, Aba', 'Eltges, Françoise', 'Queuche, Frederic', 'Renner, Julien', 'Fontanella, Jean-Michel', 'Hommel, Didier', 'Dussart, Philippe', 'Grangier, Claire', 'Djossou, Félix', 'Dacheux, Laurent', 'Goudal, Maryvonne', 'Berger, Franck', 'Ardillon, Vanessa', 'Krieger, Nicolas', 'Bourhy, Hervé', 'Spiegel, André']",PLoS Negl Trop Dis,,,False
491084a67c24a54bdafc66ed3f940274b49e80d9,PMC,"First Human Rabies Case in French Guiana, 2008: Epidemiological Investigation and Control",http://dx.doi.org/10.1371/journal.pntd.0001537,PMC3283561,22363830,CC BY,"BACKGROUND: Until 2008, human rabies had never been reported in French Guiana. On 28 May 2008, the French National Reference Center for Rabies (Institut Pasteur, Paris) confirmed the rabies diagnosis, based on hemi-nested polymerase chain reaction on skin biopsy and saliva specimens from a Guianan, who had never travelled overseas and died in Cayenne after presenting clinically typical meningoencephalitis. METHODOLOGY/PRINCIPAL FINDINGS: Molecular typing of the virus identified a Lyssavirus (Rabies virus species), closely related to those circulating in hematophagous bats (mainly Desmodus rotundus) in Latin America. A multidisciplinary Crisis Unit was activated. Its objectives were to implement an epidemiological investigation and a veterinary survey, to provide control measures and establish a communications program. The origin of the contamination was not formally established, but was probably linked to a bat bite based on the virus type isolated. After confirming exposure of 90 persons, they were vaccinated against rabies: 42 from the case's entourage and 48 healthcare workers. To handle that emergence and the local population's increased demand to be vaccinated, a specific communications program was established using several media: television, newspaper, radio. CONCLUSION/SIGNIFICANCE: This episode, occurring in the context of a Department far from continental France, strongly affected the local population, healthcare workers and authorities, and the management team faced intense pressure. This observation confirms that the risk of contracting rabies in French Guiana is real, with consequences for population educational program, control measures, medical diagnosis and post-exposure prophylaxis.",2012 Feb 21,"['Meynard, Jean-Baptiste', 'Flamand, Claude', 'Dupuy, Céline', 'Mahamat, Aba', 'Eltges, Françoise', 'Queuche, Frederic', 'Renner, Julien', 'Fontanella, Jean-Michel', 'Hommel, Didier', 'Dussart, Philippe', 'Grangier, Claire', 'Djossou, Félix', 'Dacheux, Laurent', 'Goudal, Maryvonne', 'Berger, Franck', 'Ardillon, Vanessa', 'Krieger, Nicolas', 'Bourhy, Hervé', 'Spiegel, André']",PLoS Negl Trop Dis,,,False
990fbc24eb6832897917d21d4d3d60919c7a822c,PMC,"First Human Rabies Case in French Guiana, 2008: Epidemiological Investigation and Control",http://dx.doi.org/10.1371/journal.pntd.0001537,PMC3283561,22363830,CC BY,"BACKGROUND: Until 2008, human rabies had never been reported in French Guiana. On 28 May 2008, the French National Reference Center for Rabies (Institut Pasteur, Paris) confirmed the rabies diagnosis, based on hemi-nested polymerase chain reaction on skin biopsy and saliva specimens from a Guianan, who had never travelled overseas and died in Cayenne after presenting clinically typical meningoencephalitis. METHODOLOGY/PRINCIPAL FINDINGS: Molecular typing of the virus identified a Lyssavirus (Rabies virus species), closely related to those circulating in hematophagous bats (mainly Desmodus rotundus) in Latin America. A multidisciplinary Crisis Unit was activated. Its objectives were to implement an epidemiological investigation and a veterinary survey, to provide control measures and establish a communications program. The origin of the contamination was not formally established, but was probably linked to a bat bite based on the virus type isolated. After confirming exposure of 90 persons, they were vaccinated against rabies: 42 from the case's entourage and 48 healthcare workers. To handle that emergence and the local population's increased demand to be vaccinated, a specific communications program was established using several media: television, newspaper, radio. CONCLUSION/SIGNIFICANCE: This episode, occurring in the context of a Department far from continental France, strongly affected the local population, healthcare workers and authorities, and the management team faced intense pressure. This observation confirms that the risk of contracting rabies in French Guiana is real, with consequences for population educational program, control measures, medical diagnosis and post-exposure prophylaxis.",2012 Feb 21,"['Meynard, Jean-Baptiste', 'Flamand, Claude', 'Dupuy, Céline', 'Mahamat, Aba', 'Eltges, Françoise', 'Queuche, Frederic', 'Renner, Julien', 'Fontanella, Jean-Michel', 'Hommel, Didier', 'Dussart, Philippe', 'Grangier, Claire', 'Djossou, Félix', 'Dacheux, Laurent', 'Goudal, Maryvonne', 'Berger, Franck', 'Ardillon, Vanessa', 'Krieger, Nicolas', 'Bourhy, Hervé', 'Spiegel, André']",PLoS Negl Trop Dis,,,False
1e6d38b98619d0d315d728291e97acde6c0012e1,PMC,Health System Resource Gaps and Associated Mortality from Pandemic Influenza across Six Asian Territories,http://dx.doi.org/10.1371/journal.pone.0031800,PMC3283680,22363739,CC BY,"BACKGROUND: Southeast Asia has been the focus of considerable investment in pandemic influenza preparedness. Given the wide variation in socio-economic conditions, health system capacity across the region is likely to impact to varying degrees on pandemic mitigation operations. We aimed to estimate and compare the resource gaps, and potential mortalities associated with those gaps, for responding to pandemic influenza within and between six territories in Asia. METHODS AND FINDINGS: We collected health system resource data from Cambodia, Indonesia (Jakarta and Bali), Lao PDR, Taiwan, Thailand and Vietnam. We applied a mathematical transmission model to simulate a “mild-to-moderate” pandemic influenza scenario to estimate resource needs, gaps, and attributable mortalities at province level within each territory. The results show that wide variations exist in resource capacities between and within the six territories, with substantial mortalities predicted as a result of resource gaps (referred to here as “avoidable” mortalities), particularly in poorer areas. Severe nationwide shortages of mechanical ventilators were estimated to be a major cause of avoidable mortalities in all territories except Taiwan. Other resources (oseltamivir, hospital beds and human resources) are inequitably distributed within countries. Estimates of resource gaps and avoidable mortalities were highly sensitive to model parameters defining the transmissibility and clinical severity of the pandemic scenario. However, geographic patterns observed within and across territories remained similar for the range of parameter values explored. CONCLUSIONS: The findings have important implications for where (both geographically and in terms of which resource types) investment is most needed, and the potential impact of resource mobilization for mitigating the disease burden of an influenza pandemic. Effective mobilization of resources across administrative boundaries could go some way towards minimizing avoidable deaths.",2012 Feb 21,"['Rudge, James W.', 'Hanvoravongchai, Piya', 'Krumkamp, Ralf', 'Chavez, Irwin', 'Adisasmito, Wiku', 'Ngoc Chau, Pham', 'Phommasak, Bounlay', 'Putthasri, Weerasak', 'Shih, Chin-Shui', 'Stein, Mart', 'Timen, Aura', 'Touch, Sok', 'Reintjes, Ralf', 'Coker, Richard', None]",PLoS One,,,True
05513da119ba8f48c1c468a8a40a591b731c4479,PMC,"The role of facemasks and hand hygiene in the prevention of influenza transmission in households: results from a cluster randomised trial; Berlin, Germany, 2009-2011",http://dx.doi.org/10.1186/1471-2334-12-26,PMC3285078,22280120,CC BY,"BACKGROUND: Previous controlled studies on the effect of non-pharmaceutical interventions (NPI) - namely the use of facemasks and intensified hand hygiene - in preventing household transmission of influenza have not produced definitive results. We aimed to investigate efficacy, acceptability, and tolerability of NPI in households with influenza index patients. METHODS: We conducted a cluster randomized controlled trial during the pandemic season 2009/10 and the ensuing influenza season 2010/11. We included households with an influenza positive index case in the absence of further respiratory illness within the preceding 14 days. Study arms were wearing a facemask and practicing intensified hand hygiene (MH group), wearing facemasks only (M group) and none of the two (control group). Main outcome measure was laboratory confirmed influenza infection in a household contact. We used daily questionnaires to examine adherence and tolerability of the interventions. RESULTS: We recruited 84 households (30 control, 26 M and 28 MH households) with 82, 69 and 67 household contacts, respectively. In 2009/10 all 41 index cases had a influenza A (H1N1) pdm09 infection, in 2010/11 24 had an A (H1N1) pdm09 and 20 had a B infection. The total secondary attack rate was 16% (35/218). In intention-to-treat analysis there was no statistically significant effect of the M and MH interventions on secondary infections. When analysing only households where intervention was implemented within 36 h after symptom onset of the index case, secondary infection in the pooled M and MH groups was significantly lower compared to the control group (adjusted odds ratio 0.16, 95% CI, 0.03-0.92). In a per-protocol analysis odds ratios were significantly reduced among participants of the M group (adjusted odds ratio, 0.30, 95% CI, 0.10-0.94). With the exception of MH index cases in 2010/11 adherence was good for adults and children, contacts and index cases. CONCLUSIONS: Results suggest that household transmission of influenza can be reduced by the use of NPI, such as facemasks and intensified hand hygiene, when implemented early and used diligently. Concerns about acceptability and tolerability of the interventions should not be a reason against their recommendation. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (Identifier NCT00833885).",2012 Jan 26,"['Suess, Thorsten', 'Remschmidt, Cornelius', 'Schink, Susanne B', 'Schweiger, Brunhilde', 'Nitsche, Andreas', 'Schroeder, Kati', 'Doellinger, Joerg', 'Milde, Jeanette', 'Haas, Walter', 'Koehler, Irina', 'Krause, Gérard', 'Buchholz, Udo']",BMC Infect Dis,,,True
b1d4318370f0bf32b2c6afded3ef07c1a37abe7a,PMC,First Dating of a Recombination Event in Mammalian Tick-Borne Flaviviruses,http://dx.doi.org/10.1371/journal.pone.0031981,PMC3285191,22384119,CC BY,"The mammalian tick-borne flavivirus group (MTBFG) contains viruses associated with important human and animal diseases such as encephalitis and hemorrhagic fever. In contrast to mosquito-borne flaviviruses where recombination events are frequent, the evolutionary dynamic within the MTBFG was believed to be essentially clonal. This assumption was challenged with the recent report of several homologous recombinations within the Tick-borne encephalitis virus (TBEV). We performed a thorough analysis of publicly available genomes in this group and found no compelling evidence for the previously identified recombinations. However, our results show for the first time that demonstrable recombination (i.e., with large statistical support and strong phylogenetic evidences) has occurred in the MTBFG, more specifically within the Louping ill virus lineage. Putative parents, recombinant strains and breakpoints were further tested for statistical significance using phylogenetic methods. We investigated the time of divergence between the recombinant and parental strains in a Bayesian framework. The recombination was estimated to have occurred during a window of 282 to 76 years before the present. By unravelling the temporal setting of the event, we adduce hypotheses about the ecological conditions that could account for the observed recombination.",2012 Feb 22,"['Bertrand, Yann', 'Töpel, Mats', 'Elväng, Annelie', 'Melik, Wessam', 'Johansson, Magnus']",PLoS One,,,True
28040123483f1f80ef9b612102f0b2083eac4ec4,PMC,Epstein-Barr Virus Stimulates Torque Teno Virus Replication: A Possible Relationship to Multiple Sclerosis,http://dx.doi.org/10.1371/journal.pone.0032160,PMC3285200,22384166,CC BY,"Viral infections have been implicated in the pathogenesis of multiple sclerosis. Epstein-Barr virus (EBV) has frequently been investigated as a possible candidate and torque teno virus (TTV) has also been discussed in this context. Nevertheless, mechanistic aspects remain unresolved. We report viral replication, as measured by genome amplification, as well as quantitative PCR of two TTV-HD14 isolates isolated from multiple sclerosis brain in a series of EBV-positive and -negative lymphoblastoid and Burkitt's lymphoma cell lines. Our results demonstrate the replication of both transfected TTV genomes up to day 21 post transfection in all the evaluated cell lines. Quantitative amplification indicates statistically significant enhanced TTV replication in the EBV-positive cell lines, including the EBV-converted BJAB line, in comparison to the EBV-negative Burkitt's lymphoma cell line BJAB. This suggests a helper effect of EBV infections in the replication of TTV. The present study provides information on a possible interaction of EBV and TTV in the etiology and progression of multiple sclerosis.",2012 Feb 22,"['Borkosky, Silvia S.', 'Whitley, Corinna', 'Kopp-Schneider, Annette', 'zur Hausen, Harald', 'deVilliers, Ethel-Michele']",PLoS One,,,True
ef7110a9022bac2e50c995b0f6b826ff071e48f8,PMC,Isothermal Amplification Using a Chemical Heating Device for Point-of-Care Detection of HIV-1,http://dx.doi.org/10.1371/journal.pone.0031432,PMC3285652,22384022,CC0,"BACKGROUND: To date, the use of traditional nucleic acid amplification tests (NAAT) for detection of HIV-1 DNA or RNA has been restricted to laboratory settings due to time, equipment, and technical expertise requirements. The availability of a rapid NAAT with applicability for resource-limited or point-of-care (POC) settings would fill a great need in HIV diagnostics, allowing for timely diagnosis or confirmation of infection status, as well as facilitating the diagnosis of acute infection, screening and evaluation of infants born to HIV-infected mothers. Isothermal amplification methods, such as reverse-transcription, loop-mediated isothermal amplification (RT-LAMP), exhibit characteristics that are ideal for POC settings, since they are typically quicker, easier to perform, and allow for integration into low-tech, portable heating devices. METHODOLOGY/SIGNIFICANT FINDINGS: In this study, we evaluated the HIV-1 RT-LAMP assay using portable, non-instrumented nucleic acid amplification (NINA) heating devices that generate heat from the exothermic reaction of calcium oxide and water. The NINA heating devices exhibited stable temperatures throughout the amplification reaction and consistent amplification results between three separate devices and a thermalcycler. The performance of the NINA heaters was validated using whole blood specimens from HIV-1 infected patients. CONCLUSION: The RT-LAMP isothermal amplification method used in conjunction with a chemical heating device provides a portable, rapid and robust NAAT platform that has the potential to facilitate HIV-1 testing in resource-limited settings and POC.",2012 Feb 23,"['Curtis, Kelly A.', 'Rudolph, Donna L.', 'Nejad, Irene', 'Singleton, Jered', 'Beddoe, Andy', 'Weigl, Bernhard', 'LaBarre, Paul', 'Owen, S. Michele']",PLoS One,,,True
d79628296e95343f9d5557983d7e19b66145b384,PMC,A rigorous approach to facilitate and guarantee the correctness of the genetic testing management in human genome information systems,http://dx.doi.org/10.1186/1471-2164-12-S4-S13,PMC3287582,22369688,CC BY,"BACKGROUND: Recent medical and biological technology advances have stimulated the development of new testing systems that have been providing huge, varied amounts of molecular and clinical data. Growing data volumes pose significant challenges for information processing systems in research centers. Additionally, the routines of genomics laboratory are typically characterized by high parallelism in testing and constant procedure changes. RESULTS: This paper describes a formal approach to address this challenge through the implementation of a genetic testing management system applied to human genome laboratory. We introduced the Human Genome Research Center Information System (CEGH) in Brazil, a system that is able to support constant changes in human genome testing and can provide patients updated results based on the most recent and validated genetic knowledge. Our approach uses a common repository for process planning to ensure reusability, specification, instantiation, monitoring, and execution of processes, which are defined using a relational database and rigorous control flow specifications based on process algebra (ACP). The main difference between our approach and related works is that we were able to join two important aspects: 1) process scalability achieved through relational database implementation, and 2) correctness of processes using process algebra. Furthermore, the software allows end users to define genetic testing without requiring any knowledge about business process notation or process algebra. CONCLUSIONS: This paper presents the CEGH information system that is a Laboratory Information Management System (LIMS) based on a formal framework to support genetic testing management for Mendelian disorder studies. We have proved the feasibility and showed usability benefits of a rigorous approach that is able to specify, validate, and perform genetic testing using easy end user interfaces.",2011 Dec 22,"['Araújo, Luciano V', 'Malkowski, Simon', 'Braghetto, Kelly R', 'Passos-Bueno, Maria R', 'Zatz, Mayana', 'Pu, Calton', 'Ferreira, João E']",BMC Genomics,,,True
1817050ed534376723c94abc3b5496beea55ed5b,PMC,Antimicrobial resistance and virulence factors in Escherichia coli from swedish dairy calves,http://dx.doi.org/10.1186/1751-0147-54-2,PMC3287958,22280887,CC BY,"BACKGROUND: In Sweden, knowledge about the role of enteropathogenic Escherichia coli in neonatal calf diarrhea and the occurrence of antimicrobial resistance in E. coli from young calves is largely unknown. This has therapeutic concern and such knowledge is also required for prudent use of antimicrobials. METHODS: In a case control study Esherichia coli isolated from faecal samples from dairy calves were phenotyped by biochemical fingerprinting and analyzed for virulence genes by PCR. Antimicrobial susceptibility was tested by determination of minimum inhibitory concentration (MIC). Farm management data were collected and Fisher's exact test and univariable and multivariable logistic regression analysis were performed. RESULTS: Of 95 E. coli tested for antimicrobial susceptibility 61% were resistant to one or more substances and 28% were multi-resistant. The virulence gene F5 (K99) was not found in any isolate. In total, 21 out of 40 of the investigated virulence genes were not detected or rarely detected. The virulence genes espP, irp, and fyuA were more common in resistant E. coli than in fully susceptible isolates (P < 0.05). The virulence gene terZ was associated with calf diarrhea (P ≤ 0.01). The participating 85 herds had a median herd size of 80 lactating cows. Herds with calf diarrhea problems were larger (> 55 cows; P < 0.001), had higher calf mortality (P ≤ 0.01) and calf group feeders were more in use (P < 0.05), compared to herds without calf diarrhea problems. There was no association between calf diarrhea and diversity of enteric E. coli. CONCLUSIONS: Antimicrobial resistance was common in E. coli from pre-weaned dairy calves, occurring particularly in calves from herds experiencing calf diarrhea problems. The results indicate that more factors than use of antimicrobials influence the epidemiology of resistant E. coli. Enteropathogenic E. coli seems to be an uncommon cause of neonatal calf diarrhea in Swedish dairy herds. In practice, calf diarrhea should be regarded holistically in a context of infectious agents, calf immunity, management practices etc. We therefore advice against routine antimicrobial treatment and recommend that bacteriological cultures, followed by testing for antimicrobial susceptibility and for virulence factors, are used to guide decisions on such treatment.",2012 Jan 26,"['de Verdier, Kerstin', 'Nyman, Ann', 'Greko, Christina', 'Bengtsson, Björn']",Acta Vet Scand,,,True
4cc4711e7794e52f303fdd8557dd175e71989c7b,PMC,Dectin-1 and DC-SIGN Polymorphisms Associated with Invasive Pulmonary Aspergillosis Infection,http://dx.doi.org/10.1371/journal.pone.0032273,PMC3288082,22384201,CC BY,"The recognition of pathogen-derived structures by C-type lectins and the chemotactic activity mediated by the CCL2/CCR2 axis are critical steps in determining the host immune response to fungi. The present study was designed to investigate whether the presence of single nucleotide polymorphisms (SNPs) within DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing Invasive Pulmonary Aspergillosis (IPA). Twenty-seven SNPs were selected using a hybrid functional/tagging approach and genotyped in 182 haematological patients, fifty-seven of them diagnosed with proven or probable IPA according to the 2008 EORTC/MSG criteria. Association analysis revealed that carriers of the Dectin-1 (rs3901533 T/T) and Dectin-1 (rs7309123 G/G) genotypes and DC-SIGN (rs4804800 G), DC-SIGN (rs11465384 T), DC-SIGN (7248637 A) and DC-SIGN (7252229 C) alleles had a significantly increased risk of IPA infection (OR = 5.59 95%CI 1.37–22.77; OR = 4.91 95%CI 1.52–15.89; OR = 2.75 95%CI 1.27–5.95; OR = 2.70 95%CI 1.24–5.90; OR = 2.39 95%CI 1.09–5.22 and OR = 2.05 95%CI 1.00–4.22, respectively). There was also a significantly increased frequency of galactomannan positivity among patients carrying the Dectin-1 (rs3901533_T) allele and Dectin-1 (rs7309123_G/G) genotype. In addition, healthy individuals with this latter genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers, suggesting a role of the Dectin-1 (rs7309123) polymorphism in determining the levels of Dectin-1 and, consequently, the level of susceptibility to IPA infection. SNP-SNP interaction (epistasis) analysis revealed significant interactions models including SNPs in Dectin-1, Dectin-2, CCL2 and CCR2 genes, with synergistic genetic effects. Although these results need to be further validated in larger cohorts, they suggest that Dectin-1, DC-SIGN, Dectin-2, CCL2 and CCR2 genetic variants influence the risk of IPA infection and might be useful in developing a risk-adapted prophylaxis.",2012 Feb 27,"['Sainz, Juan', 'Lupiáñez, Carmen Belén', 'Segura-Catena, Juana', 'Vazquez, Lourdes', 'Ríos, Rafael', 'Oyonarte, Salvador', 'Hemminki, Kari', 'Försti, Asta', 'Jurado, Manuel']",PLoS One,,,True
6f62efb20f820241aeb1a8e16af68502fedc9b43,PMC,GmPHD5 acts as an important regulator for crosstalk between histone H3K4 di-methylation and H3K14 acetylation in response to salinity stress in soybean,http://dx.doi.org/10.1186/1471-2229-11-178,PMC3288756,22168212,CC BY,"BACKGROUND: Accumulated evidence suggest that specific patterns of histone posttranslational modifications (PTMs) and their crosstalks may determine transcriptional outcomes. However, the regulatory mechanisms of these ""histone codes"" in plants remain largely unknown. RESULTS: In this study, we demonstrate for the first time that a salinity stress inducible PHD (plant homeodomain) finger domain containing protein GmPHD5 can read the ""histone code"" underlying the methylated H3K4. GmPHD5 interacts with other DNA binding proteins, including GmGNAT1 (an acetyl transferase), GmElongin A (a transcription elongation factor) and GmISWI (a chromatin remodeling protein). Our results suggest that GmPHD5 can recognize specific histone methylated H3K4, with preference to di-methylated H3K4. Here, we illustrate that the interaction between GmPHD5 and GmGNAT1 is regulated by the self-acetylation of GmGNAT1, which can also acetylate histone H3. GmGNAT1 exhibits a preference toward acetylated histone H3K14. These results suggest a histone crosstalk between methylated H3K4 and acetylated H3K14. Consistent to its putative roles in gene regulation under salinity stress, we showed that GmPHD5 can bind to the promoters of some confirmed salinity inducible genes in soybean. CONCLUSION: Here, we propose a model suggesting that the nuclear protein GmPHD5 is capable of regulating the crosstalk between histone methylation and histone acetylation of different lysine residues. Nevertheless, GmPHD5 could also recruit chromatin remodeling factors and transcription factors of salt stress inducible genes to regulate their expression in response to salinity stress.",2011 Dec 15,"['Wu, Tao', 'Pi, Er-Xu', 'Tsai, Sau-Na', 'Lam, Hon-Ming', 'Sun, Sai-Ming', 'Kwan, Yiu Wa', 'Ngai, Sai-Ming']",BMC Plant Biol,,,True
495132370917fdb1762cd47fa73e9e6ff94a60b6,PMC,Development and Characterization of a Reverse Genetic System for Studying Dengue Virus Serotype 3 Strain Variation and Neutralization,http://dx.doi.org/10.1371/journal.pntd.0001486,PMC3289595,22389731,CC BY,"Dengue viruses (DENV) are enveloped single-stranded positive-sense RNA viruses transmitted by Aedes spp. mosquitoes. There are four genetically distinct serotypes designated DENV-1 through DENV-4, each further subdivided into distinct genotypes. The dengue scientific community has long contended that infection with one serotype confers lifelong protection against subsequent infection with the same serotype, irrespective of virus genotype. However this hypothesis is under increased scrutiny and the role of DENV genotypic variation in protection from repeated infection is less certain. As dengue vaccine trials move increasingly into field-testing, there is an urgent need to develop tools to better define the role of genotypic variation in DENV infection and immunity. To better understand genotypic variation in DENV-3 neutralization and protection, we designed and constructed a panel of isogenic, recombinant DENV-3 infectious clones, each expressing an envelope glycoprotein from a different DENV-3 genotype; Philippines 1982 (genotype I), Thailand 1995 (genotype II), Sri Lanka 1989 and Cuba 2002 (genotype III) and Puerto Rico 1977 (genotype IV). We used the panel to explore how natural envelope variation influences DENV-polyclonal serum interactions. When the recombinant viruses were tested in neutralization assays using immune sera from primary DENV infections, neutralization titers varied by as much as ∼19-fold, depending on the expressed envelope glycoprotein. The observed variability in neutralization titers suggests that relatively few residue changes in the E glycoprotein may have significant effects on DENV specific humoral immunity and influence antibody mediated protection or disease enhancement in the setting of both natural infection and vaccination. These genotypic differences are also likely to be important in temporal and spatial microevolution of DENV-3 in the background of heterotypic neutralization. The recombinant and synthetic tools described here are valuable for testing hypotheses on genetic determinants of DENV-3 immunopathogenesis.",2012 Feb 28,"['Messer, William B.', 'Yount, Boyd', 'Hacker, Kari E.', 'Donaldson, Eric F.', 'Huynh, Jeremy P.', 'de Silva, Aravinda M.', 'Baric, Ralph S.']",PLoS Negl Trop Dis,,,True
f2615e2f1b1e1de90023706bf99405151406bbd8,PMC,Etiology and Clinical Characterization of Respiratory Virus Infections in Adult Patients Attending an Emergency Department in Beijing,http://dx.doi.org/10.1371/journal.pone.0032174,PMC3289638,22389685,CC BY,"BACKGROUND: Acute respiratory tract infections (ARTIs) represent a serious global health burden. To date, few reports have addressed the prevalence of respiratory viruses (RVs) in adults with ARTIs attending an emergency department (ED). Therefore, the potential impact of respiratory virus infections on such patients remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: To determine the epidemiological and clinical profiles of common and recently discovered respiratory viruses in adults with ARTIs attending an ED in Beijing, a 1-year consecutive study was conducted from May, 2010, to April, 2011. Nose and throat swab samples from 416 ARTI patients were checked for 13 respiratory viruses using multiple reverse transcription polymerase chain reaction(RT-PCR) assays for common respiratory viruses, including influenza viruses (Flu) A, B, and adenoviruses (ADVs), picornaviruses (PICs), respiratory syncytial virus (RSV), parainfluenza viruses (PIVs) 1–3, combined with real-time RT-PCR for human metapneumovirus (HMPV) and human coronaviruses (HCoVs, -OC43, -229E, -NL63, and -HKU1). Viral pathogens were detected in 52.88% (220/416) of patient samples, and 7.21% (30/416) of patients tested positive for more than one virus. PICs (17.79%) were the dominant agents detected, followed by FluA (16.11%), HCoVs (11.78%), and ADV (11.30%). HMPV, PIVs, and FluB were also detected (<3%), but not RSV. The total prevalence and the dominant virus infections detected differed significantly between ours and a previous report. Co-infection rates were high for HCoV-229E (12/39, 30.76%), PIC (22/74, 29.73%), ADV (12/47, 25.53%) and FluA (15/67, 22.39%). Different patterns of clinical symptoms were associated with different respiratory viruses. CONCLUSIONS: The pattern of RV involvement in adults with ARTIs attending an ED in China differs from that previously reported. The high prevalence of viruses (PIC, FluA, HCoVs and ADV) reported here strongly highlight the need for the development of safe and effective therapeutic approaches for these viruses.",2012 Feb 28,"['Yu, Xiaoyan', 'Lu, Roujian', 'Wang, Zhong', 'Zhu, Na', 'Wang, Wen', 'Julian, Druce', 'Chris, Birch', 'Lv, Jianxin', 'Tan, Wenjie']",PLoS One,,,True
6ea1978890ab099e90e61ddf078b6d983e60b07f,PMC,Repertoire of Intensive Care Unit Pneumonia Microbiota,http://dx.doi.org/10.1371/journal.pone.0032486,PMC3289664,22389704,CC BY,"Despite the considerable number of studies reported to date, the causative agents of pneumonia are not completely identified. We comprehensively applied modern and traditional laboratory diagnostic techniques to identify microbiota in patients who were admitted to or developed pneumonia in intensive care units (ICUs). During a three-year period, we tested the bronchoalveolar lavage (BAL) of patients with ventilator-associated pneumonia, community-acquired pneumonia, non-ventilator ICU pneumonia and aspiration pneumonia, and compared the results with those from patients without pneumonia (controls). Samples were tested by amplification of 16S rDNA, 18S rDNA genes followed by cloning and sequencing and by PCR to target specific pathogens. We also included culture, amoeba co-culture, detection of antibodies to selected agents and urinary antigen tests. Based on molecular testing, we identified a wide repertoire of 160 bacterial species of which 73 have not been previously reported in pneumonia. Moreover, we found 37 putative new bacterial phylotypes with a 16S rDNA gene divergence ≥98% from known phylotypes. We also identified 24 fungal species of which 6 have not been previously reported in pneumonia and 7 viruses. Patients can present up to 16 different microorganisms in a single BAL (mean ± SD; 3.77±2.93). Some pathogens considered to be typical for ICU pneumonia such as Pseudomonas aeruginosa and Streptococcus species can be detected as commonly in controls as in pneumonia patients which strikingly highlights the existence of a core pulmonary microbiota. Differences in the microbiota of different forms of pneumonia were documented.",2012 Feb 28,"['Bousbia, Sabri', 'Papazian, Laurent', 'Saux, Pierre', 'Forel, Jean Marie', 'Auffray, Jean-Pierre', 'Martin, Claude', 'Raoult, Didier', 'La Scola, Bernard']",PLoS One,,,True
a086b50101fcfa29f699b41cbf034ae71ac70bff,PMC,Discovery and Genomic Characterization of Noroviruses from a Gastroenteritis Outbreak in Domestic Cats in the US,http://dx.doi.org/10.1371/journal.pone.0032739,PMC3289677,22389721,CC BY,"Norovirus (NoV) RNA was detected in the stools of 6 out 14 (42.8%) 8–12-week-old cats with enteritis from a feline shelter, in New York State. Upon sequence analysis of the complete capsid, the six NoVs were found to be identical, suggesting the spread of a unique NoV strain in the shelter. The full-length genomic sequence (7839 nt) of one feline NoV, CU081210E/2010/US, was determined. In the capsid protein VP1 region, the virus displayed the highest amino acid identity to animal genogroup IV genotype 2 (GIV.2) NoVs: lion/Pistoia-387/06/IT (97.9%) and dog/Bari-170/07/IT (90.4%). These findings document the discovery of a novel feline calicivirus, different from vesiviruses, and extend the spectrum of NoV host range. Epidemiological studies using feline NoV-specific diagnostic tools and experimental infection of cats are required to understand whether NoVs have a pathogenic role in this species.",2012 Feb 28,"['Pinto, Pierfrancesco', 'Wang, Qiuhong', 'Chen, Ning', 'Dubovi, Edward J.', 'Daniels, Joshua B.', 'Millward, Laurie M.', 'Buonavoglia, Canio', 'Martella, Vito', 'Saif, Linda J.']",PLoS One,,,True
fff1e7b356f0d6cf7b28b019974833200e38f843,PMC,Clinical Manifestations Vary with Different Age Spectrums in Infants with Kawasaki Disease,http://dx.doi.org/10.1100/2012/210382,PMC3289979,22454602,CC BY,"Background. Kawasaki disease (KD) is an acute systemic vasculitis with unknown etiology. The diagnosis of KD depends on clinical manifestations. The prevalence of coronary artery abnormality (CAA) is 11.0% and results in cardiac sequelae, such as myocardial infarction or coronary aneurysm, which are the most serious complications in KD. Methods. We divided KD's children into different age groups: ≤6 months old, 7 months to 1 year old, and >1 year old, respectively. Different parameters were compared in each group. Results. Infants ≤6 months old are less likely to fulfill KD's major diagnostic criteria within 10 days, are prone to develop incomplete KD with the lowest cholesterol level, and have the greatest chance to have CAA and the laboratory features associated with CAA, such as the longest time needed to confirm CA diagnosis, lower hemoglobin level, lower albumin level, and higher platelet count. Infants <1 year old develop higher percentage of leukocytosis and sterile pyuria. But this group has fewer patients with neck lymphadenopathy.",2012 Feb 15,"['Liu, Hao-Chuan', 'Lo, Chiao-Wei', 'Hwang, Betau', 'Lee, Pi-Chang']",ScientificWorldJournal,,,True
86e3f31b72109395a9dd02071bf83aeb7fa6803c,PMC,Lethal Nipah Virus Infection Induces Rapid Overexpression of CXCL10,http://dx.doi.org/10.1371/journal.pone.0032157,PMC3290546,22393386,CC BY,"Nipah virus (NiV) is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10), an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication. Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections. This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis.",2012 Feb 29,"['Mathieu, Cyrille', 'Guillaume, Vanessa', 'Sabine, Amélie', 'Ong, Kien Chai', 'Wong, Kum Thong', 'Legras-Lachuer, Catherine', 'Horvat, Branka']",PLoS One,,,True
5881e62ed1be0eec6603b49cf10c413d3c1e560f,PMC,Influenza Virus Respiratory Infection and Transmission Following Ocular Inoculation in Ferrets,http://dx.doi.org/10.1371/journal.ppat.1002569,PMC3291616,22396651,CC0,"While influenza viruses are a common respiratory pathogen, sporadic reports of conjunctivitis following human infection demonstrates the ability of this virus to cause disease outside of the respiratory tract. The ocular surface represents both a potential site of virus replication and a portal of entry for establishment of a respiratory infection. However, the properties which govern ocular tropism of influenza viruses, the mechanisms of virus spread from ocular to respiratory tissue, and the potential differences in respiratory disease initiated from different exposure routes are poorly understood. Here, we established a ferret model of ocular inoculation to explore the development of virus pathogenicity and transmissibility following influenza virus exposure by the ocular route. We found that multiple subtypes of human and avian influenza viruses mounted a productive virus infection in the upper respiratory tract of ferrets following ocular inoculation, and were additionally detected in ocular tissue during the acute phase of infection. H5N1 viruses maintained their ability for systemic spread and lethal infection following inoculation by the ocular route. Replication-independent deposition of virus inoculum from ocular to respiratory tissue was limited to the nares and upper trachea, unlike traditional intranasal inoculation which results in virus deposition in both upper and lower respiratory tract tissues. Despite high titers of replicating transmissible seasonal viruses in the upper respiratory tract of ferrets inoculated by the ocular route, virus transmissibility to naïve contacts by respiratory droplets was reduced following ocular inoculation. These data improve our understanding of the mechanisms of virus spread following ocular exposure and highlight differences in the establishment of respiratory disease and virus transmissibility following use of different inoculation volumes and routes.",2012 Mar 1,"['Belser, Jessica A.', 'Gustin, Kortney M.', 'Maines, Taronna R.', 'Pantin-Jackwood, Mary J.', 'Katz, Jacqueline M.', 'Tumpey, Terrence M.']",PLoS Pathog,,,True
3ba2641160cb0acdca16991443017f11d2d848c2,PMC,Critical Role of Perforin-dependent CD8+ T Cell Immunity for Rapid Protective Vaccination in a Murine Model for Human Smallpox,http://dx.doi.org/10.1371/journal.ppat.1002557,PMC3291617,22396645,CC BY,"Vaccination is highly effective in preventing various infectious diseases, whereas the constant threat of new emerging pathogens necessitates the development of innovative vaccination principles that also confer rapid protection in a case of emergency. Although increasing evidence points to T cell immunity playing a critical role in vaccination against viral diseases, vaccine efficacy is mostly associated with the induction of antibody responses. Here we analyze the immunological mechanism(s) of rapidly protective vaccinia virus immunization using mousepox as surrogate model for human smallpox. We found that fast protection against lethal systemic poxvirus disease solely depended on CD4 and CD8 T cell responses induced by vaccination with highly attenuated modified vaccinia virus Ankara (MVA) or conventional vaccinia virus. Of note, CD4 T cells were critically required to allow for MVA induced CD8 T cell expansion and perforin-mediated cytotoxicity was a key mechanism of MVA induced protection. In contrast, selected components of the innate immune system and B cell-mediated responses were fully dispensable for prevention of fatal disease by immunization given two days before challenge. In conclusion, our data clearly demonstrate that perforin-dependent CD8 T cell immunity plays a key role in MVA conferred short term protection against lethal mousepox. Rapid induction of T cell immunity might serve as a new paradigm for treatments that need to fit into a scenario of protective emergency vaccination.",2012 Mar 1,"['Kremer, Melanie', 'Suezer, Yasemin', 'Volz, Asisa', 'Frenz, Theresa', 'Majzoub, Monir', 'Hanschmann, Kay-Martin', 'Lehmann, Michael H.', 'Kalinke, Ulrich', 'Sutter, Gerd']",PLoS Pathog,,,True
3e035bd3c87d15ec4bca05cd13551c70d1bc5e78,PMC,Placement of Leucine Zipper Motifs at the Carboxyl Terminus of HIV-1 Protease Significantly Reduces Virion Production,http://dx.doi.org/10.1371/journal.pone.0032845,PMC3291649,22396796,CC BY,"Natural HIV-1 protease (PR) is homodimeric. Some researchers believe that interactions between HIV-1 Gag-Pol molecules trigger the activation of embedded PR (which mediates Gag and Gag-Pol cleavage), and that Gag-Pol assembly domains outside of PR may contribute to PR activation by influencing PR dimer interaction in a Gag-Pol context. To determine if the enhancement of PR dimer interaction facilitates PR activation, we placed single or tandem repeat leucine zippers (LZ) at the PR C-terminus, and looked for a correlation between enhanced Gag processing efficiency and increased Gag-PR-LZ multimerization capacity. We found significant reductions in virus-like particles (VLPs) produced by HIV-1 mutants, with LZ fused to the end of PR as a result of enhanced Gag cleavage efficiency. Since VLP production can be restored to wt levels following PR activity inhibition, this assembly defect is considered PR activity-dependent. We also found a correlation between the LZ enhancement effect on Gag cleavage and enhanced Gag-PR multimerization. The results suggest that PR dimer interactions facilitated by forced Gag-PR multimerization lead to premature Gag cleavage, likely a result of premature PR activation. Our conclusion is that placement of a heterologous dimerization domain downstream of PR enhances PR-mediated Gag cleavage efficiency, implying that structural conformation, rather than the primary sequence outside of PR, is a major determinant of HIV-1 PR activation.",2012 Mar 1,"['Pan, Yen-Yu', 'Wang, Shiu-Mei', 'Huang, Kuo-Jung', 'Chiang, Chien-Cheng', 'Wang, Chin-Tien']",PLoS One,,,True
650c105dc3718ea36a7abffa0de7f9068390045f,PMC,A20 (Tnfaip3) Deficiency in Myeloid Cells Protects against Influenza A Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1002570,PMC3291650,22396652,CC BY,"The innate immune response provides the first line of defense against viruses and other pathogens by responding to specific microbial molecules. Influenza A virus (IAV) produces double-stranded RNA as an intermediate during the replication life cycle, which activates the intracellular pathogen recognition receptor RIG-I and induces the production of proinflammatory cytokines and antiviral interferon. Understanding the mechanisms that regulate innate immune responses to IAV and other viruses is of key importance to develop novel therapeutic strategies. Here we used myeloid cell specific A20 knockout mice to examine the role of the ubiquitin-editing protein A20 in the response of myeloid cells to IAV infection. A20 deficient macrophages were hyperresponsive to double stranded RNA and IAV infection, as illustrated by enhanced NF-κB and IRF3 activation, concomitant with increased production of proinflammatory cytokines, chemokines and type I interferon. In vivo this was associated with an increased number of alveolar macrophages and neutrophils in the lungs of IAV infected mice. Surprisingly, myeloid cell specific A20 knockout mice are protected against lethal IAV infection. These results challenge the general belief that an excessive host proinflammatory response is associated with IAV-induced lethality, and suggest that under certain conditions inhibition of A20 might be of interest in the management of IAV infections.",2012 Mar 1,"['Maelfait, Jonathan', 'Roose, Kenny', 'Bogaert, Pieter', 'Sze, Mozes', 'Saelens, Xavier', 'Pasparakis, Manolis', 'Carpentier, Isabelle', 'van Loo, Geert', 'Beyaert, Rudi']",PLoS Pathog,,,True
953e146785a16b34f944a8dacec8816d0df49e0c,PMC,"Antibody-Based Sensors: Principles, Problems and Potential for Detection of Pathogens and Associated Toxins",http://dx.doi.org/10.3390/s90604407,PMC3291918,22408533,CC BY,"Antibody-based sensors permit the rapid and sensitive analysis of a range of pathogens and associated toxins. A critical assessment of the implementation of such formats is provided, with reference to their principles, problems and potential for ‘on-site’ analysis. Particular emphasis is placed on the detection of foodborne bacterial pathogens, such as Escherichia coli and Listeria monocytogenes, and additional examples relating to the monitoring of fungal pathogens, viruses, mycotoxins, marine toxins and parasites are also provided.",2009 Jun 5,"['Byrne, Barry', 'Stack, Edwina', 'Gilmartin, Niamh', ""O'Kennedy, Richard""]",Sensors (Basel),,,True
058c0fc94ded8fa4e7a302081c3ea738d16a4b1a,PMC,Using Support Vector Machine and Evolutionary Profiles to Predict Antifreeze Protein Sequences,http://dx.doi.org/10.3390/ijms13022196,PMC3292016,22408447,CC BY,"Antifreeze proteins (AFPs) are ice-binding proteins. Accurate identification of new AFPs is important in understanding ice-protein interactions and creating novel ice-binding domains in other proteins. In this paper, an accurate method, called AFP_PSSM, has been developed for predicting antifreeze proteins using a support vector machine (SVM) and position specific scoring matrix (PSSM) profiles. This is the first study in which evolutionary information in the form of PSSM profiles has been successfully used for predicting antifreeze proteins. Tested by 10-fold cross validation and independent test, the accuracy of the proposed method reaches 82.67% for the training dataset and 93.01% for the testing dataset, respectively. These results indicate that our predictor is a useful tool for predicting antifreeze proteins. A web server (AFP_PSSM) that implements the proposed predictor is freely available.",2012 Feb 17,"['Zhao, Xiaowei', 'Ma, Zhiqiang', 'Yin, Minghao']",Int J Mol Sci,,,True
a3a0db5c445f85527672a6402d35269c06ce8f6b,PMC,Using Support Vector Machine and Evolutionary Profiles to Predict Antifreeze Protein Sequences,http://dx.doi.org/10.3390/ijms13022196,PMC3292016,22408447,CC BY,"Antifreeze proteins (AFPs) are ice-binding proteins. Accurate identification of new AFPs is important in understanding ice-protein interactions and creating novel ice-binding domains in other proteins. In this paper, an accurate method, called AFP_PSSM, has been developed for predicting antifreeze proteins using a support vector machine (SVM) and position specific scoring matrix (PSSM) profiles. This is the first study in which evolutionary information in the form of PSSM profiles has been successfully used for predicting antifreeze proteins. Tested by 10-fold cross validation and independent test, the accuracy of the proposed method reaches 82.67% for the training dataset and 93.01% for the testing dataset, respectively. These results indicate that our predictor is a useful tool for predicting antifreeze proteins. A web server (AFP_PSSM) that implements the proposed predictor is freely available.",2012 Feb 17,"['Zhao, Xiaowei', 'Ma, Zhiqiang', 'Yin, Minghao']",Int J Mol Sci,,,False
cfdac27f152143ecfce91f501ea6a992be428333,PMC,Reliability and External Validity of AMSTAR in Assessing Quality of TCM Systematic Reviews,http://dx.doi.org/10.1155/2012/732195,PMC3292204,22454679,CC BY,"Objective. The aim of this study is to measure the reliability and external validity of AMSTAR by applying it to a sample of TCM systematic reviews. Study Design and Methods. We tested the agreement, reliability, construct validity, and feasibility of AMSTAR through comparisons with OQAQ. Statistical analyses were performed by using SPSS 13.0. Results. A random of sample with 41 TCM systematic reviews was selected from a database. The interrater agreement of the individual items of AMSTAR was moderate with a mean kappa of 0.50 (95% CI: 0.26, 0.73). The ICC for AMSTAR against OQAQ (total score of 9 items, excluding item 10) was 0.87 (95% CI: 0.76, 0.93). Conclusions. Although there is room for improvement on few items, the new tool is reliable, valid, and easy to use for methodological quality assessment of systematic reviews on TCM.",2012 Feb 16,"['Kang, Deying', 'Wu, Yuxia', 'Hu, Dan', 'Hong, Qi', 'Wang, Jialiang', 'Zhang, Xin']",Evid Based Complement Alternat Med,,,True
03e9a22249dd6e201e347bb87cf96a931120f5c5,PMC,Rapid Screening for Entry Inhibitors of Highly Pathogenic Viruses under Low-Level Biocontainment,http://dx.doi.org/10.1371/journal.pone.0030538,PMC3292545,22396728,CC BY,"Emerging viruses including Nipah, Hendra, Lujo, and Junin viruses have enormous potential to spread rapidly. Nipah virus, after emerging as a zoonosis, has also evolved the capacity for human-to-human transmission. Most of the diseases caused by these pathogens are untreatable and require high biocontainment conditions. Universal methods for rapidly identifying and screening candidate antivirals are urgently needed. We have developed a modular antiviral platform strategy that relies on simple bioinformatic and genetic information about each pathogen. Central to this platform is the use of envelope glycoprotein cDNAs to establish multi-cycle replication systems under BSL2 conditions for viral pathogens that normally require BSL3 and BSL4 facilities. We generated monoclonal antibodies against Nipah G by cDNA immunization in rats, and we showed that these antibodies neutralize both Nipah and Hendra live viruses. We then used these effective Henipavirus inhibitors to validate our screening strategy. Our proposed strategy should contribute to the response capability for emerging infectious diseases, providing a way to initiate antiviral development immediately upon identifying novel viruses.",2012 Mar 2,"['Talekar, Aparna', 'Pessi, Antonello', 'Glickman, Fraser', 'Sengupta, Uttara', 'Briese, Thomas', 'Whitt, Michael A.', 'Mathieu, Cyrille', 'Horvat, Branka', 'Moscona, Anne', 'Porotto, Matteo']",PLoS One,,,True
3ed4b5616c342d7185015a8553a8f8350511ca21,PMC,Infection control management of patients with suspected highly infectious diseases in emergency departments: data from a survey in 41 facilities in 14 European countries,http://dx.doi.org/10.1186/1471-2334-12-27,PMC3292988,22284435,CC BY,"BACKGROUND: In Emergency and Medical Admission Departments (EDs and MADs), prompt recognition and appropriate infection control management of patients with Highly Infectious Diseases (HIDs, e.g. Viral Hemorrhagic Fevers and SARS) are fundamental for avoiding nosocomial outbreaks. METHODS: The EuroNHID (European Network for Highly Infectious Diseases) project collected data from 41 EDs and MADs in 14 European countries, located in the same facility as a national/regional referral centre for HIDs, using specifically developed checklists, during on-site visits from February to November 2009. RESULTS: Isolation rooms were available in 34 facilities (82,9%): these rooms had anteroom in 19, dedicated entrance in 15, negative pressure in 17, and HEPA filtration of exhausting air in 12. Only 6 centres (14,6%) had isolation rooms with all characteristics. Personnel trained for the recognition of HIDs was available in 24 facilities; management protocols for HIDs were available in 35. CONCLUSIONS: Preparedness level for the safe and appropriate management of HIDs is partially adequate in the surveyed EDs and MADs.",2012 Jan 28,"['Fusco, Francesco M', 'Schilling, Stefan', 'De Iaco, Giuseppina', 'Brodt, Hans-Reinhard', 'Brouqui, Philippe', 'Maltezou, Helena C', 'Bannister, Barbara', 'Gottschalk, René', 'Thomson, Gail', 'Puro, Vincenzo', 'Ippolito, Giuseppe', None]",BMC Infect Dis,,,True
c5078be94c34f8a7357c2b4a9e5ea3c19ecb45e2,PMC,"Use of Sensitive, Broad-Spectrum Molecular Assays and Human Airway Epithelium Cultures for Detection of Respiratory Pathogens",http://dx.doi.org/10.1371/journal.pone.0032582,PMC3293820,22403676,CC BY,"Rapid and accurate detection and identification of viruses causing respiratory tract infections is important for patient care and disease control. Despite the fact that several assays are available, identification of an etiological agent is not possible in ∼30% of patients suffering from respiratory tract diseases. Therefore, the aim of the current study was to develop a diagnostic set for the detection of respiratory viruses with sensitivity as low as 1–10 copies per reaction. Evaluation of the assay using a training clinical sample set showed that viral nucleic acids were identified in ∼76% of cases. To improve assay performance and facilitate the identification of novel species or emerging strains, cultures of fully differentiated human airway epithelium were used to pre-amplify infectious viruses. This additional step resulted in the detection of pathogens in all samples tested. Based on these results it can be hypothesized that the lack of an etiological agent in some clinical samples, both reported previously and observed in the present study, may result not only from the presence of unknown viral species, but also from imperfections in the detection methods used.",2012 Mar 5,"['Pyrc, Krzysztof', 'Stożek, Karol', 'Wojcik, Krzysztof', 'Gawron, Katarzyna', 'Zeglen, Slawomir', 'Karolak, Wojciech', 'Wojarski, Jacek', 'Ochman, Marek', 'Hubalewska-Mazgaj, Magdalena', 'Bochenek, Grazyna', 'Sanak, Marek', 'Zembala, Marian', 'Szczeklik, Andrzej', 'Potempa, Jan']",PLoS One,,,True
f093aa0cf1ddef303ec4c049ab0be105587dd92c,PMC,Mapping Climate Change Vulnerabilities to Infectious Diseases in Europe,http://dx.doi.org/10.1289/ehp.1103805,PMC3295348,22113877,CC0,"Background: The incidence, outbreak frequency, and distribution of many infectious diseases are generally expected to change as a consequence of climate change, yet there is limited regional information available to guide decision making. Objective: We surveyed government officials designated as Competent Bodies for Scientific Advice concerning infectious diseases to examine the degree to which they are concerned about potential effects of climate change on infectious diseases, as well as their perceptions of institutional capacities in their respective countries. Methods: In 2007 and 2009/2010, national infectious disease experts from 30 European Economic Area countries were surveyed about recent and projected infectious disease patterns in relation to climate change in their countries and the national capacity to cope with them. Results: A large majority of respondents agreed that climate change would affect vector-borne (86% of country representatives), food-borne (70%), water-borne (68%), and rodent-borne (68%) diseases in their countries. In addition, most indicated that institutional improvements are needed for ongoing surveillance programs (83%), collaboration with the veterinary sector (69%), management of animal disease outbreaks (66%), national monitoring and control of climate-sensitive infectious diseases (64%), health services during an infectious disease outbreak (61%), and diagnostic support during an epidemic (54%). Conclusions: Expert responses were generally consistent with the peer-reviewed literature regarding the relationship between climate change and vector- and water-borne diseases, but were less so for food-borne diseases. Shortcomings in institutional capacity to manage climate change vulnerability, identified in this assessment, should be addressed in impact, vulnerability, and adaptation assessments.",2012 Mar 23,"['Semenza, Jan C.', 'Suk, Jonathan E.', 'Estevez, Virginia', 'Ebi, Kristie L.', 'Lindgren, Elisabet']",Environ Health Perspect,,,True
64a0b8711c7e7553c8025dc56a843ce601fc029b,PMC,Early Clinical Features of Dengue Virus Infection in Nicaraguan Children: A Longitudinal Analysis,http://dx.doi.org/10.1371/journal.pntd.0001562,PMC3295819,22413033,CC BY,"BACKGROUND: Tens of millions of dengue cases and approximately 500,000 life-threatening complications occur annually. New tools are needed to distinguish dengue from other febrile illnesses. In addition, the natural history of pediatric dengue early in illness in a community-based setting has not been well-defined. METHODS: Data from the multi-year, ongoing Pediatric Dengue Cohort Study of approximately 3,800 children aged 2–14 years in Managua, Nicaragua, were used to examine the frequency of clinical signs and symptoms by day of illness and to generate models for the association of signs and symptoms during the early phase of illness and over the entire course of illness with testing dengue-positive. Odds ratios (ORs) and 95% confidence intervals were calculated using generalized estimating equations (GEE) for repeated measures, adjusting for age and gender. RESULTS: One-fourth of children who tested dengue-positive did not meet the WHO case definition for suspected dengue. The frequency of signs and symptoms varied by day of illness, dengue status, and disease severity. Multivariable GEE models showed increased odds of testing dengue-positive associated with fever, headache, retro-orbital pain, myalgia, arthralgia, rash, petechiae, positive tourniquet test, vomiting, leukopenia, platelets ≤150,000 cells/mL, poor capillary refill, cold extremities and hypotension. Estimated ORs tended to be higher for signs and symptoms over the course of illness compared to the early phase of illness. CONCLUSIONS: Day-by-day analysis of clinical signs and symptoms together with longitudinal statistical analysis showed significant associations with testing dengue-positive and important differences during the early phase of illness compared to the entire course of illness. These findings stress the importance of considering day of illness when developing prediction algorithms for real-time clinical management.",2012 Mar 6,"['Biswas, Hope H.', 'Ortega, Oscar', 'Gordon, Aubree', 'Standish, Katherine', 'Balmaseda, Angel', 'Kuan, Guillermina', 'Harris, Eva']",PLoS Negl Trop Dis,,,True
b0988e41e28d6f9269e7198ec419142d0a81c7a3,PMC,Enhanced inhibition of Avian leukosis virus subgroup J replication by multi-target miRNAs,http://dx.doi.org/10.1186/1743-422X-8-556,PMC3296551,22188662,CC BY,"BACKGROUND: Avian leukosis virus (ALV) is a major infectious disease that impacts the poultry industry worldwide. Despite intensive efforts, no effective vaccine has been developed against ALV because of mutations that lead to resistant forms. Therefore, there is a dire need to develop antiviral agents for the treatment of ALV infections and RNA interference (RNAi) is considered an effective antiviral strategy. RESULTS: In this study, the avian leukosis virus subgroup J (ALV-J) proviral genome, including the gag genes, were treated as targets for RNAi. Four pairs of miRNA sequences were designed and synthesized that targeted different regions of the gag gene. The screened target (i.e., the gag genes) was shown to effectively suppress the replication of ALV-J by 19.0-77.3%. To avoid the generation of escape variants during virus infection, expression vectors of multi-target miRNAs were constructed using the multi-target serial strategy (against different regions of the gag, pol, and env genes). Multi-target miRNAs were shown to play a synergistic role in the inhibition of ALV-J replication, with an inhibition efficiency of viral replication ranging from 85.0-91.2%. CONCLUSION: The strategy of multi-target miRNAs might be an effective method for inhibiting ALV replication and the acquisition of resistant mutations.",2011 Dec 22,"['Meng, Qing-Wen', 'Zhang, Zai-Ping', 'Wang, Wei', 'Tian, Jin', 'Xiao, Zhi-Guang']",Virol J,,,True
67f2ba141bcc1bffbd19f77b1aedde25a0f0022b,PMC,Hospital incident command system (HICS) performance in Iran; decision making during disasters,http://dx.doi.org/10.1186/1757-7241-20-14,PMC3296571,22309772,CC BY,"BACKGROUND: Hospitals are cornerstones for health care in a community and must continue to function in the face of a disaster. The Hospital Incident Command System (HICS) is a method by which the hospital operates when an emergency is declared. Hospitals are often ill equipped to evaluate the strengths and vulnerabilities of their own management systems before the occurrence of an actual disaster. The main objective of this study was to measure the decision making performance according to HICS job actions sheets using tabletop exercises. METHODS: This observational study was conducted between May 1st 2008 and August 31st 2009. Twenty three Iranian hospitals were included. A tabletop exercise was developed for each hospital which in turn was based on the highest probable risk. The job action sheets of the HICS were used as measurements of performance. Each indicator was considered as 1, 2 or 3 in accordance with the HICS. Fair performance was determined as < 40%; intermediate as 41-70%; high as 71-100% of the maximum score of 192. Descriptive statistics, T-test, and Univariate Analysis of Variance were used. RESULTS: None of the participating hospitals had a hospital disaster management plan. The performance according to HICS was intermediate for 83% (n = 19) of the participating hospitals. No hospital had a high level of performance. The performance level for the individual sections was intermediate or fair, except for the logistic and finance sections which demonstrated a higher level of performance. The public hospitals had overall higher performances than university hospitals (P = 0.04). CONCLUSIONS: The decision making performance in the Iranian hospitals, as measured during table top exercises and using the indicators proposed by HICS was intermediate to poor. In addition, this study demonstrates that the HICS job action sheets can be used as a template for measuring the hospital response. Simulations can be used to assess preparedness, but the correlation with outcome remains to be studied.",2012 Feb 6,"['Djalali, Ahmadreza', 'Castren, Maaret', 'Hosseinijenab, Vahid', 'Khatib, Mahmoud', 'Ohlen, Gunnar', 'Kurland, Lisa']",Scand J Trauma Resusc Emerg Med,,,True
a67a570efab57b9f2492a652c0c17f47546416c4,PMC,Reverse Genetics of SARS-Related Coronavirus Using Vaccinia Virus-Based Recombination,http://dx.doi.org/10.1371/journal.pone.0032857,PMC3296753,22412934,CC BY,"Severe acute respiratory syndrome (SARS) is a zoonotic disease caused by SARS-related coronavirus (SARS-CoV) that emerged in 2002 to become a global health concern. Although the original outbreak was controlled by classical public health measures, there is a real risk that another SARS-CoV could re-emerge from its natural reservoir, either in its original form or as a more virulent or pathogenic strain; in which case, the virus would be difficult to control in the absence of any effective antiviral drugs or vaccines. Using the well-studied SARS-CoV isolate HKU-39849, we developed a vaccinia virus-based SARS-CoV reverse genetic system that is both robust and biosafe. The SARS-CoV genome was cloned in separate vaccinia virus vectors, (vSARS-CoV-5prime and vSARS-CoV-3prime) as two cDNAs that were subsequently ligated to create a genome-length SARS-CoV cDNA template for in vitro transcription of SARS-CoV infectious RNA transcripts. Transfection of the RNA transcripts into permissive cells led to the recovery of infectious virus (recSARS-CoV). Characterization of the plaques produced by recSARS-CoV showed that they were similar in size to the parental SARS-CoV isolate HKU-39849 but smaller than the SARS-CoV isolate Frankfurt-1. Comparative analysis of replication kinetics showed that the kinetics of recSARS-CoV replication are similar to those of SARS-CoV Frankfurt-1, although the titers of virus released into the culture supernatant are approximately 10-fold less. The reverse genetic system was finally used to generate a recSARS-CoV reporter virus expressing Renilla luciferase in order to facilitate the analysis of SARS-CoV gene expression in human dendritic cells (hDCs). In parallel, a Renilla luciferase gene was also inserted into the genome of human coronavirus 229E (HCoV-229E). Using this approach, we demonstrate that, in contrast to HCoV-229E, SARS-CoV is not able to mediate efficient heterologous gene expression in hDCs.",2012 Mar 7,"['van den Worm, Sjoerd H. E.', 'Eriksson, Klara Kristin', 'Zevenhoven, Jessika C.', 'Weber, Friedemann', 'Züst, Roland', 'Kuri, Thomas', 'Dijkman, Ronald', 'Chang, Guohui', 'Siddell, Stuart G.', 'Snijder, Eric J.', 'Thiel, Volker', 'Davidson, Andrew D.']",PLoS One,,,True
5d7698a990270f5ebfa2c879d56187116acc7646,PMC,A placebo-controlled trial of Korean red ginseng extract for preventing Influenza-like illness in healthy adults,http://dx.doi.org/10.1186/1472-6882-12-10,PMC3297520,22314101,CC BY,"ABSTRACTS: BACKGROUND: Standardized Korean red ginseng extract has become the best-selling influenza-like illness (ILI) remedy in Korea, yet much controversy regarding the efficacy of the Korean red ginseng (KRG) in reducing ILI incidence remains. The aim of the study is to assess the efficacy of the KRG extract on the ILI incidence in healthy adults. METHODS/DESIGN: We will conduct a randomized, double-blind, placebo-controlled study at the onset of the influenza seasons. A total of 100 subjects 30-70 years of age will be recruited from the general populations. The subjects will be instructed to take 9 capsules per day of either the KRG extract or a placebo for a period of 3 months. The primary outcome measure is to assess the frequency of ILI onset in participated subjects. Secondary variable measures will be included severity and duration of ILI symptoms. The ILI symptoms will be scored by subjects using a 4-point scale. DISCUSSION: This study is a randomized placebo controlled trial to evaluate the efficacy of the KRG extract compared to placebo and will be provided valuable new information about the clinical and physiological effects of the KRG extract on reduction of ILI incidence including flu and upper respiratory tract infections. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if KRG extract can be shown to be an effective reduction strategy in ILI incidence. TRIAL REGISTRATION: NCT01478009.",2012 Feb 8,"['Ha, Ki-Chan', 'Kim, Min-Gul', 'Oh, Mi-Ra', 'Choi, Eun-Kyung', 'Back, Hyang-Im', 'Kim, Sun-Young', 'Park, Eun-Ok', 'Kwon, Dae-Young', 'Yang, Hye-Jeong', 'Kim, Min-Jeong', 'Kang, Hee-Joo', 'Lee, Ju-Hyung', 'Choi, Kyung-Min', 'Chae, Soo-Wan', 'Lee, Chang-Seop']",BMC Complement Altern Med,,,True
1a12f8004e57cbdc497edada74fdfd8431f4a9eb,PMC,A chemokine gene expression signature derived from meta-analysis predicts the pathogenicity of viral respiratory infections,http://dx.doi.org/10.1186/1752-0509-5-202,PMC3297540,22189154,CC BY,"BACKGROUND: During respiratory viral infections host injury occurs due in part to inappropriate host responses. In this study we sought to uncover the host transcriptional responses underlying differences between high- and low-pathogenic infections. RESULTS: From a compendium of 12 studies that included responses to influenza A subtype H5N1, reconstructed 1918 influenza A virus, and SARS coronavirus, we used meta-analysis to derive multiple gene expression signatures. We compared these signatures by their capacity to segregate biological conditions by pathogenicity and predict pathogenicity in a test data set. The highest-performing signature was expressed as a continuum in low-, medium-, and high-pathogenicity samples, suggesting a direct, analog relationship between expression and pathogenicity. This signature comprised 57 genes including a subnetwork of chemokines, implicating dysregulated cell recruitment in injury. CONCLUSIONS: Highly pathogenic viruses elicit expression of many of the same key genes as lower pathogenic viruses but to a higher degree. This increased degree of expression may result in the uncontrolled co-localization of inflammatory cell types and lead to irreversible host damage.",2011 Dec 22,"['Chang, Stewart T', 'Tchitchek, Nicolas', 'Ghosh, Debashis', 'Benecke, Arndt', 'Katze, Michael G']",BMC Syst Biol,,,True
86fca5af635ee9425e3375140fb48cbe6d429411,PMC,Deep Sequencing for the Detection of Virus-Like Sequences in the Brains of Patients with Multiple Sclerosis: Detection of GBV-C in Human Brain,http://dx.doi.org/10.1371/journal.pone.0031886,PMC3297595,22412845,CC BY,"Multiple sclerosis (MS) is a demyelinating disease of unknown origin that affects the central nervous system of an estimated 400,000 Americans. GBV-C or hepatitis G is a flavivirus that is found in the serum of 1–2% of blood donors. It was originally associated with hepatitis, but is now believed to be a relatively non-pathogenic lymphotropic virus. Fifty frozen specimens from the brains of deceased persons affected by MS were obtained along with 15 normal control brain specimens. RNA was extracted and ribosomal RNAs were depleted before sequencing on the Illumina GAII. These 36 bp reads were compared with a non-redundant database derived from the 600,000+ viral sequences in GenBank organized into 4080 taxa. An individual read successfully aligned to the viral database was considered to be a “hit”. Normalized MS specimen hit rates for each viral taxon were compared to the distribution of hits in the normal controls. Seventeen MS and 11 control brain extracts were sequenced, yielding 4–10 million sequences (“reads”) each. Over-representation of sequence from at least one of 12 viral taxa was observed in 7 of the 17 MS samples. Sequences resembling other viruses previously implicated in the pathogenesis of MS were not significantly enriched in any of the diseased brain specimens. Sequences from GB virus C (GBV-C), a flavivirus not previously isolated from brain, were enriched in one of the MS samples. GBV-C in this brain specimen was confirmed by specific amplification in this single MS brain specimen, but not in the 30 other MS brain samples available. The entire 9.4 kb sequence of this GBV-C isolate is reported here. This study shows the feasibility of deep sequencing for the detection of occult viral infections in the brains of deceased persons with MS. The first isolation of GBV-C from human brain is reported here.",2012 Mar 8,"['Kriesel, John D.', 'Hobbs, Maurine R.', 'Jones, Brandt B.', 'Milash, Brett', 'Nagra, Rashed M.', 'Fischer, Kael F.']",PLoS One,,,True
09ccb3b9fece55e72c3acb85c4259de62a9c9e0c,PMC,Association of herd BRSV and BHV-1 seroprevalence with respiratory disease and reproductive performance in adult dairy cattle,http://dx.doi.org/10.1186/1751-0147-54-4,PMC3298528,22289165,CC BY,"BACKGROUND: The aim of this study was to detect the associations between bovine herpesvirus 1 (BHV-1) status of a herd and respiratory disease (BRD) occurrence and reproductive performance in pregnant heifers and cows. The association between management-related factors and higher BRD occurrence was also estimated. METHODS: Serum samples, collected from cows and youngstock from 103 dairy cattle herds, were analyzed for antibodies against BHV-1, bovine respiratory syncytial virus (BRSV), bovine viral diarrhoea virus (BVDV), and Mycoplasma bovis. A questionnaire was used to collect data concerning herd management factors and reproductive performance, as well as the occurrence of clinical signs of respiratory disease in the last two years, as evaluated by the veterinarian or farm manager. Multiple correspondence analysis (MCA) and logistic regression analysis were performed to identify and quantify the risk factors. RESULTS: A low to moderate prevalence (1-49%) of BRSV antibodies among youngstock was associated with a high occurrence of respiratory disease (OR = 6.2, p = 0.010) in cows and in-calf heifers. Employees of the farm may participate in the spread of such disease. Larger herd size, loose-housing of cows, housing youngstock separately from cows until pregnancy, and purchasing new animals were factors possibly related to a high occurrence of respiratory disease symptoms in pregnant heifers and cows. The highest risk of abortions (> 1.3%) and increased insemination index (number of inseminations per pregnancy) (> 1.9) occurred in herds with a moderate prevalence of BHV-1 antibodies (1-49%) in cows. CONCLUSIONS: BHV-1 was not associated with acute respiratory disease in adult dairy cattle, however was significantly related to reproductive performance. BRSV possesses the main role in respiratory disease complex in adult dairy cattle.",2012 Jan 30,"['Raaperi, Kerli', 'Bougeard, Stephanie', 'Aleksejev, Annely', 'Orro, Toomas', 'Viltrop, Arvo']",Acta Vet Scand,,,True
6b749617eb4a9f2760720a1b2a061cd0d45f9e3f,PMC,Enhancement of anti-murine colon cancer immunity by fusion of a SARS fragment to a low-immunogenic carcinoembryonic antigen,http://dx.doi.org/10.1186/1480-9222-14-2,PMC3298716,22304896,CC BY,"BACKGROUND: It is widely understood that tumor cells express tumor-associated antigens (TAAs), of which many are usually in low immunogenicity; for example, carcinoembryonic antigen (CEA) is specifically expressed on human colon cancer cells and is viewed as a low-immunogenic TAA. How to activate host immunity against specific TAAs and to suppress tumor growth therefore becomes important in cancer therapy development. RESULTS: To enhance the immune efficiency of CEA in mice that received, we fused a partial CEA gene with exogenous SARS-CoV fragments. Oral vaccination of an attenuated Salmonella typhimurium strain transformed with plasmids encoding CEA-SARS-CoV fusion gene into BALB/c mice elicited significant increases in TNF-α and IL-10 in the serum. In addition, a smaller tumor volume was observed in CT26/CEA-bearing mice who received CEA-SARS-CoV gene therapy in comparison with those administered CEA alone. CONCLUSION: The administration of fusing CEA-SARS-CoV fragments may provide a promising strategy for strengthening the anti-tumor efficacy against low-immunogenic endogenous tumor antigens.",2012 Feb 3,"['Lin, Chen-Si', 'Kao, Shih-Han', 'Chen, Yu-Cheng', 'Li, Chi-Han', 'Hsieh, Yuan-Ting', 'Yang, Shang-Chih', 'Wu, Chang-Jer', 'Lee, Ru-Ping', 'Liao, Kuang-Wen']",Biol Proced Online,,,True
9151f784207180e12703758211d31c6d0ee84423,PMC,Evaluation of immune responses to porcine reproductive and respiratory syndrome virus in pigs during early stage of infection under farm conditions,http://dx.doi.org/10.1186/1743-422X-9-45,PMC3298799,22340040,CC BY,"BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) causes chronic, economically devastating disease in pigs of all ages. Frequent mutations in the viral genome result in viruses with immune escape mutants. Irrespective of regular vaccination, control of PRRSV remains a challenge to swine farmers. In PRRSV-infected pigs, innate cytokine IFN-α is inhibited and the adaptive arm of the immunity is delayed. To elucidate both cellular and innate cytokine responses at very early stages of PRRSV infection, seven weeks old pigs maintained on a commercial pig farm were infected and analyzed. RESULTS: One pig in a pen containing 25 pigs was PRRSV infected and responses from this pig and one penmate were assessed two days later. All the infected and a few of the contact neighbor pigs were viremic. At day 2 post-infection, approximately 50% of viremic pigs had greater than 50% reduction in NK cell-mediated cytotoxicity, and nearly a 1-fold increase in IFN-α production was detected in blood of a few pigs. Enhanced secretion of IL-4 (in ~90%), IL-12 (in ~40%), and IL-10 (in ~20%) (but not IFN-γ) in PRRSV infected pigs was observed. In addition, reduced frequency of myeloid cells, CD4(-)CD8(+ )T cells, and CD4(+)CD8(+ )T cells and upregulated frequency of lymphocytes bearing natural T regulatory cell phenotype were detected in viremic pigs. Interestingly, all viremic contact pigs also had comparable immune cell modulations. CONCLUSION: Replicating PRRSV in both infected and contact pigs was found to be responsible for rapid modulation in NK cell-meditated cytotoxicity and alteration in the production of important immune cytokines. PRRSV-induced immunological changes observed simultaneously at both cellular and cytokine levels early post-infection appear to be responsible for the delay in generation of adaptive immunity. As the study was performed in pigs maintained under commercial environmental conditions, this study has practical implications in design of protective vaccines.",2012 Feb 16,"['Dwivedi, Varun', 'Manickam, Cordelia', 'Binjawadagi, Basavaraj', 'Linhares, Daniel', 'Murtaugh, Michael P', 'Renukaradhya, Gourapura J']",Virol J,,,True
210ebd55fd095ff2fb393e871fea70815a9ead75,PMC,RNA interference targeting virion core protein ORF095 inhibits Goatpox virus replication in Vero cells,http://dx.doi.org/10.1186/1743-422X-9-48,PMC3298800,22340205,CC BY,"BACKGROUND: Goatpox is an economically important disease in goat and sheep-producing areas of the world. Many vaccine strategies developed to control the disease are not yet completely successful. Hairpin expression vectors have been used to induce gene silencing in a large number of studies on viruses. However, none of these studies has been attempted to study GTPV. In the interest of exploiting improved methods to control goat pox, it is participated that RNAi may provide effective protection against GTPV. In this study we show the suppression of Goatpox virus (GTPV) replication via knockdown of virion core protein using RNA interference. RESULTS: Four short interfering RNA (siRNA) sequences (siRNA-61, siRNA-70, siRNA-165 and siRNA-296) against a region of GTPV ORF095 were selected. Sense and antisense siRNA-encoding sequences separated by a hairpin loop sequence were designed as short hairpin RNA (shRNA) expression cassettes under the control of a human U6 promoter. ORF095 amplicon was generated using PCR, and then cloned into pEGFP-N1 vector, named as p095/EGFP. p095/EGFP and each of the siRNA expression cassettes (p61, p70, p165 and p296) were co-transfected into BHK-21 cells. Fluorescence detection, flow cytometric analysis, retro transcription PCR (RT-PCR) and real time PCR were used to check the efficiency of RNAi. The results showed that the ORF095-specific siRNA-70 effectively down-regulated the expression of ORF095. When Vero cells were transfected with shRNA expression vectors (p61/GFP, p70/GFP, p165/GFP and p296/GFP) and then infected with GTPV, GTPV-ORF095-70 was found to be the most effective inhibition site in decreasing cytopathic effect (CPE) induced by GTPV. The results presented here indicated that DNA-based siRNA could effectively inhibit the replication of GTPV (approximately 463. 5-fold reduction of viral titers) on Vero cells. CONCLUSIONS: This study demonstrates that vector-based shRNA methodology can effectively inhibit GTPV replication on Vero cells. Simultaneously, this work represents a strategy for controlling goatpox, potentially facilitating new experimental approaches in the analysis of both viral and cellular gene functions during of GTPV infection.",2012 Feb 17,"['Zhao, Zhixun', 'Wu, Guohua', 'Zhu, Xueliang', 'Yan, Xinmin', 'Dou, Yongxi', 'Li, Jian', 'Zhu, Haixia', 'Zhang, Qiang', 'Cai, Xuepeng']",Virol J,,,True
6b20f25b48785e488fb280a76ec8f1da3bf8e2a0,PMC,Resveratrol Inhibits KSHV Reactivation by Lowering the Levels of Cellular EGR-1,http://dx.doi.org/10.1371/journal.pone.0033364,PMC3299779,22428032,CC BY,"In the field of herpesvirus research, the exact molecular mechanism by which such viruses reactivate from latency remains elusive. Kaposi's sarcoma-associated herpesvirus (KSHV) primarily exists in a latent state, while only 1–3% of cells support lytic infection at any specific time. KSHV reactivation from latency is an exceedingly intricate process mediated by the integration of viral and cellular factors. Previously, our lab has described early growth response-1 (Egr-1) as an essential component for the KSHV reactivation process via its ability to mediate transcription of KSHV ORF50, the gene encoding for replication and transcription activator (RTA), a viral component known to control the switch from latent to lytic infection. In here, electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) experiments revealed that Egr-1 binds KSHV ORF50 promoter (ORF50P) in at least two different GC-rich binding domains. Expression profiles of cellular egr-1 and KSHV-encoded ORF50 follow a similar pattern during de novo KSHV infection. Over-expressing Egr-1, a signaling component downstream of Raf>MEK>ERK1/2, in KSHV-infected cells activates KSHV lytic replication. Through performing more physiologically relevant experiments, we analyzed the effect of a dietary supplement containing resveratrol on KSHV-infected cells. Our results, for the first time, demonstrate resveratrol to act in lowering ERK1/2 activity and expression of Egr-1 in KSHV-infected cells, resulting in the suppression of virus reactivation from latency. Taken together, these findings will undoubtedly contribute to future studies on not only combating KSHV related disease conditions, but also on other herpesviruses-induced pathogenesis.",2012 Mar 12,"['Dyson, Ossie F.', 'Walker, Lia R.', 'Whitehouse, Adrian', 'Cook, Paul P.', 'Akula, Shaw M.']",PLoS One,,,True
aa89440c172e206c9cdd2f77373ed2b4d1a6b975,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,True
eedef997878564c9d1bd4c183b47daf16d94b52b,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
8051974f7fec24ba5c8dbdf3d5e5b18bfe18c32f,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
f160d134af9e408a52589be1dd6930387d63e288,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
1eefce8aeb42f9e7f7dbe2cc126c89ef74b7c3f5,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
78e91bc7155b4224150017b25ab97804f6c72031,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
44c09bd45e9cee534cfd848c7d182f7dfbbf1e42,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
9fd90139397a0f97a1d5f0caafb98b4f43ced130,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
5679834ba10a936a2f80d6b86bdc9ef3c150a37a,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
71b8d5b1b6326d49737ff53f2e846ed5e1a1bf66,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
7483b73912b2aed3addf19d4f44f45f4b2dcb669,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
f86fb93797c28a8667c57817a5b3cc73454e05f1,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
3f8919e9a281276e8d3acdb9050c88c4000abee7,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
d3ae818d64c0e37d7235d1acbecef4364a460c2b,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
e9d32ac6db6f898b035aab6d4357342c3ae2442b,PMC,A Surveillance System to Reduce Transmission of Pandemic H1N1 (2009) Influenza in a 2600-Bed Medical Center,http://dx.doi.org/10.1371/journal.pone.0032731,PMC3302803,22427871,CC BY,"BACKGROUND: Concerns have been raised about how the transmission of emerging infectious diseases from patients to healthcare workers (HCWs) and vice versa could be recognized and prevented in a timely manner. An effective strategy to block transmission of pandemic H1N1 (2009) influenza in HCWs is important. METHODOLOGY/PRINCIPAL FINDINGS: An infection control program was implemented to survey and prevent nosocomial outbreaks of H1N1 (2009) influenza at a 2,600-bed, tertiary-care academic hospital. In total, 4,963 employees at Kaohsiung Chang Gung Memorial Hospital recorded their temperature and received online education on control practices for influenza infections. Administration records provided vaccination records and occupational characteristics of all HCWs. Early recognition of a pandemic H1N1 (2009) influenza case was followed by a semi-structured questionnaire to analyze possible routes of patient contact, household contact, or unspecified contact. Surveillance spanned August 1, 2009 to January 31, 2010; 51 HCWs were confirmed to have novel H1N1 (2009) influenza by quantitative real-time reverse transcription polymerase chain reaction. Prevalence of patient contact, household contact, or unspecified contact infection was 13.7% (7/51), 13.7% (7/51), and 72.5% (37/51), respectively. The prevalence of the novel H1N1 infection was significantly lower among vaccinated HCWs than among unvaccinated HCWs (p<0.001). Higher viral loads in throat swabs were found in HCWs with patient and household contact infection than in those with unspecified contact infection (4.15 vs. 3.53 copies/mL, log(10), p = 0.035). CONCLUSION: A surveillance system with daily temperature recordings and online education for HCWs is important for a low attack rate of H1N1 (2009) influenza transmission before H1N1 (2009) influenza vaccination is available, and the attack rate is further decreased after mass vaccination. Unspecified contact infection rates were significantly higher than that of patient contact and household contact infection, highlighting the need for public education of influenza transmission in addition to hospital infection control.",2012 Mar 13,"['Chu, Tsui-Ping', 'Li, Chung-Chen', 'Wang, Lin', 'Hsu, Li-Wen', 'Eng, Hock-Liew', 'You, Huey-Ling', 'Liu, Jien-Wei', 'Wei, Chi-Chen', 'Chang, Ling-Sai', 'Lee, Ing-Kit', 'Yang, Kuender D.']",PLoS One,,,True
5ac423d77382c035d9ba1f51ed94d524d1a9ec7f,PMC,Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis,http://dx.doi.org/10.1371/journal.pone.0033174,PMC3303816,22432004,CC BY,"BACKGROUND: Pandemic and seasonal respiratory viruses are a major global health concern. Given the genetic diversity of respiratory viruses and the emergence of drug resistant strains, the targeted disruption of human host-virus interactions is a potential therapeutic strategy for treating multi-viral infections. The availability of large-scale genomic datasets focused on host-pathogen interactions can be used to discover novel drug targets as well as potential opportunities for drug repositioning. METHODS/RESULTS: In this study, we performed a large-scale analysis of microarray datasets involving host response to infections by influenza A virus, respiratory syncytial virus, rhinovirus, SARS-coronavirus, metapneumonia virus, coxsackievirus and cytomegalovirus. Common genes and pathways were found through a rigorous, iterative analysis pipeline where relevant host mRNA expression datasets were identified, analyzed for quality and gene differential expression, then mapped to pathways for enrichment analysis. Possible repurposed drugs targets were found through database and literature searches. A total of 67 common biological pathways were identified among the seven different respiratory viruses analyzed, representing fifteen laboratories, nine different cell types, and seven different array platforms. A large overlap in the general immune response was observed among the top twenty of these 67 pathways, adding validation to our analysis strategy. Of the top five pathways, we found 53 differentially expressed genes affected by at least five of the seven viruses. We suggest five new therapeutic indications for existing small molecules or biological agents targeting proteins encoded by the genes F3, IL1B, TNF, CASP1 and MMP9. Pathway enrichment analysis also identified a potential novel host response, the Parkin-Ubiquitin Proteasomal System (Parkin-UPS) pathway, which is known to be involved in the progression of neurodegenerative Parkinson's disease. CONCLUSIONS: Our study suggests that multiple and diverse respiratory viruses invoke several common host response pathways. Further analysis of these pathways suggests potential opportunities for therapeutic intervention.",2012 Mar 14,"['Smith, Steven B.', 'Dampier, William', 'Tozeren, Aydin', 'Brown, James R.', 'Magid-Slav, Michal']",PLoS One,,,True
2305cbae32a50cf9923356cd30ca3152944d6d38,PMC,Both TLR2 and TRIF Contribute to Interferon-β Production during Listeria Infection,http://dx.doi.org/10.1371/journal.pone.0033299,PMC3303824,22432012,CC BY,"Synthesis of interferon-β (IFN-β) is an innate response to cytoplasmic infection with bacterial pathogens. Our recent studies showed that Listeria monocytogenes limits immune detection and IFN-β synthesis via deacetylation of its peptidoglycan, which renders the bacterium resistant to lysozyme degradation. Here, we examined signaling requirements for the massive IFN-β production resulting from the infection of murine macrophages with a mutant strain of L. monocytogenes, ΔpgdA, which is unable to modify its peptidoglycan. We report the identification of unconventional signaling pathways to the IFN-β gene, requiring TLR2 and bacterial internalization. Induction of IFN-β was independent of the Mal/TIRAP adaptor protein but required TRIF and the transcription factors IRF3 and IRF7. These pathways were stimulated to a lesser degree by wild-type L. monocytogenes. They operated in both resident and inflammatory macrophages derived from the peritoneal cavity, but not in bone marrow-derived macrophages. The novelty of our findings thus lies in the first description of TLR2 and TRIF as two critical components leading to the induction of the IFN-β gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-β gene expression.",2012 Mar 14,"['Aubry, Camille', 'Corr, Sinéad C.', 'Wienerroither, Sebastian', 'Goulard, Céline', 'Jones, Ruth', 'Jamieson, Amanda M.', 'Decker, Thomas', ""O'Neill, Luke A. J."", 'Dussurget, Olivier', 'Cossart, Pascale']",PLoS One,,,True
59f0dcb0a9c96b60a795162ec2230238896a96e3,PMC,Impact of Preexisting Adenovirus Vector Immunity on Immunogenicity and Protection Conferred with an Adenovirus-Based H5N1 Influenza Vaccine,http://dx.doi.org/10.1371/journal.pone.0033428,PMC3303828,22432020,CC0,"The prevalence of preexisting immunity to adenoviruses in the majority of the human population might adversely impact the development of adaptive immune responses against adenovirus vector-based vaccines. To address this issue, we primed BALB/c mice either intranasally (i.n.) or intramuscularly (i.m.) with varying doses of wild type (WT) human adenovirus subtype 5 (HAd5). Following the development of immunity against HAd5, we immunized animals via the i.n. or i.m. route of inoculation with a HAd vector (HAd-HA-NP) expressing the hemagglutinin (HA) and nucleoprotein (NP) of A/Vietnam/1203/04 (H5N1) influenza virus. The immunogenicity and protection results suggest that low levels of vector immunity (<520 virus-neutralization titer) induced by priming mice with up to 10(7) plaque forming units (p.f.u.) of HAd-WT did not adversely impact the protective efficacy of the vaccine. Furthermore, high levels of vector immunity (approximately 1500 virus-neutralization titer) induced by priming mice with 10(8) p.f.u. of HAd-WT were overcome by either increasing the vaccine dose or using alternate routes of vaccination. A further increase in the priming dose to 10(9) p.f.u. allowed only partial protection. These results suggest possible strategies to overcome the variable levels of human immunity against adenoviruses, leading to better utilization of HAd vector-based vaccines.",2012 Mar 14,"['Pandey, Aseem', 'Singh, Neetu', 'Vemula, Sai V.', 'Couëtil, Laurent', 'Katz, Jacqueline M.', 'Donis, Ruben', 'Sambhara, Suryaprakash', 'Mittal, Suresh K.']",PLoS One,,,True
7b00b9f04112c671d8c31227d31b3fea7ca10c7e,PMC,Protein Reporter Bioassay Systems for the Phenotypic Screening of Candidate Drugs: A Mouse Platform for Anti-Aging Drug Screening,http://dx.doi.org/10.3390/s120201648,PMC3304132,22438730,CC BY,"Recent drug discovery efforts have utilized high throughput screening (HTS) of large chemical libraries to identify compounds that modify the activity of discrete molecular targets. The molecular target approach to drug screening is widely used in the pharmaceutical and biotechnology industries, because of the amount of knowledge now available regarding protein structure that has been obtained by computer simulation. The molecular target approach requires that the structure of target molecules, and an understanding of their physiological functions, is known. This approach to drug discovery may, however, limit the identification of novel drugs. As an alternative, the phenotypic- or pathway-screening approach to drug discovery is gaining popularity, particularly in the academic sector. This approach not only provides the opportunity to identify promising drug candidates, but also enables novel information regarding biological pathways to be unveiled. Reporter assays are a powerful tool for the phenotypic screening of compound libraries. Of the various reporter genes that can be used in such assays, those encoding secreted proteins enable the screening of hit molecules in both living cells and animals. Cell- and animal-based screens enable simultaneous evaluation of drug metabolism or toxicity with biological activity. Therefore, drug candidates identified in these screens may have increased biological efficacy and a lower risk of side effects in humans. In this article, we review the reporter bioassay systems available for phenotypic drug discovery.",2012 Feb 7,"['Chiba, Takuya', 'Tsuchiya, Tomoshi', 'Mori, Ryoichi', 'Shimokawa, Isao']",Sensors (Basel),,,True
ef2b8f83d5a3ab8ae35e4b51fea6d3ed9eb49122,PMC,Development of an ELISA-array for simultaneous detection of five encephalitis viruses,http://dx.doi.org/10.1186/1743-422X-9-56,PMC3305475,22369052,CC BY,"Japanese encephalitis virus(JEV), tick-borne encephalitis virus(TBEV), and eastern equine encephalitis virus (EEEV) can cause symptoms of encephalitis. Establishment of accurate and easy methods by which to detect these viruses is essential for the prevention and treatment of associated infectious diseases. Currently, there are still no multiple antigen detection methods available clinically. An ELISA-array, which detects multiple antigens, is easy to handle, and inexpensive, has enormous potential in pathogen detection. An ELISA-array method for the simultaneous detection of five encephalitis viruses was developed in this study. Seven monoclonal antibodies against five encephalitis-associated viruses were prepared and used for development of the ELISA-array. The ELISA-array assay is based on a ""sandwich"" ELISA format and consists of viral antibodies printed directly on 96-well microtiter plates, allowing for direct detection of 5 viruses. The developed ELISA-array proved to have similar specificity and higher sensitivity compared with the conventional ELISAs. This method was validated by different viral cultures and three chicken eggs inoculated with infected patient serum. The results demonstrated that the developed ELISA-array is sensitive and easy to use, which would have potential for clinical use.",2012 Feb 27,"['Kang, Xiaoping', 'Li, Yuchang', 'Fan, Li', 'Lin, Fang', 'Wei, Jingjing', 'Zhu, Xiaolei', 'Hu, Yi', 'Li, Jing', 'Chang, Guohui', 'Zhu, Qingyu', 'Liu, Hong', 'Yang, Yinhui']",Virol J,,,True
70c53ce121228fdd6ba78b20f143736b56f71984,PMC,CXCR7 antagonism prevents axonal injury during experimental autoimmune encephalomyelitis as revealed by in vivo axial diffusivity,http://dx.doi.org/10.1186/1742-2094-8-170,PMC3305694,22145790,CC BY,"BACKGROUND: Multiple Sclerosis (MS) is characterized by the pathological trafficking of leukocytes into the central nervous system (CNS). Using the murine MS model, experimental autoimmune encephalomyelitis (EAE), we previously demonstrated that antagonism of the chemokine receptor CXCR7 blocks endothelial cell sequestration of CXCL12, thereby enhancing the abluminal localization of CXCR4-expressing leukocytes. CXCR7 antagonism led to decreased parenchymal entry of leukocytes and amelioration of ongoing disease during EAE. Of note, animals that received high doses of CXCR7 antagonist recovered to baseline function, as assessed by standard clinical scoring. Because functional recovery reflects axonal integrity, we utilized diffusion tensor imaging (DTI) to evaluate axonal injury in CXCR7 antagonist- versus vehicle-treated mice after recovery from EAE. METHODS: C57BL6/J mice underwent adoptive transfer of MOG-reactive Th1 cells and were treated daily with either CXCR7 antagonist or vehicle for 28 days; and then evaluated by DTI to assess for axonal injury. After imaging, spinal cords underwent histological analysis of myelin and oligodendrocytes via staining with luxol fast blue (LFB), and immunofluorescence for myelin basic protein (MBP) and glutathione S-transferase-π (GST-π). Detection of non-phosphorylated neurofilament H (NH-F) was also performed to detect injured axons. Statistical analysis for EAE scores, DTI parameters and non-phosphorylated NH-F immunofluorescence were done by ANOVA followed by Bonferroni post-hoc test. For all statistical analysis a p < 0.05 was considered significant. RESULTS: In vivo DTI maps of spinal cord ventrolateral white matter (VLWM) axial diffusivities of naïve and CXCR7 antagonist-treated mice were indistinguishable, while vehicle-treated animals exhibited decreased axial diffusivities. Quantitative differences in injured axons, as assessed via detection of non-phosphorylated NH-F, were consistent with axial diffusivity measurements. Overall, qualitative myelin content and presence of oligodendrocytes were similar in all treatment groups, as expected by their radial diffusivity values. Quantitative assessment of persistent inflammatory infiltrates revealed significant decreases within the parenchyma of CXCR7 antagonist-treated mice versus controls. CONCLUSIONS: These data suggest that CXCR7 antagonism not only prevents persistent inflammation but also preserves axonal integrity. Thus, targeting CXCR7 modifies both disease severity and recovery during EAE, suggesting a role for this molecule in both phases of disease.",2011 Dec 6,"['Cruz-Orengo, Lillian', 'Chen, Ying-Jr', 'Kim, Joong Hee', 'Dorsey, Denise', 'Song, Sheng-Kwei', 'Klein, Robyn S']",J Neuroinflammation,,,True
ba3f5979fe991711ff096116b05cdb182ef3aeab,PMC,A Novel High-Throughput Vaccinia Virus Neutralization Assay and Preexisting Immunity in Populations from Different Geographic Regions in China,http://dx.doi.org/10.1371/journal.pone.0033392,PMC3306400,22438922,CC BY,"BACKGROUND: Pre-existing immunity to Vaccinia Tian Tan virus (VTT) resulting from a large vaccination campaign against smallpox prior to the early 1980s in China, has been a major issue for application of VTT-vector based vaccines. It is essential to establish a sensitive and high-throughput neutralization assay to understand the epidemiology of Vaccinia-specific immunity in current populations in China. METHODOLOGY/PRINCIPAL FINDINGS: A new anti-Vaccinia virus (VACV) neutralization assay that used the attenuated replication-competent VTT carrying the firefly luciferase gene of Photinus pyralis (rTV-Fluc) was established and standardized for critical parameters that included the choice of cell line, viral infection dose, and the infection time. The current study evaluated the maintenance of virus-specific immunity after smallpox vaccination by conducting a non-randomized, cross-sectional analysis of antiviral antibody-mediated immune responses in volunteers examined 30–55 years after vaccination. The rTV-Fluc neutralization assay was able to detect neutralizing antibodies (NAbs) against Vaccinia virus without the ability to differentiate strains of Vaccinia virus. We showed that the neutralizing titers measured by our assay were similar to those obtained by the traditional plaque reduction neutralization test (PRNT). Using this assay, we found a low prevalence of NAb to VTT (7.6%) in individuals born before 1980 from Beijing and Anhui provinces in China, and when present, anti-VTT NAb titers were low. No NAbs were detected in all 222 samples from individuals born after 1980. There was no significant difference observed for titer or prevalence by gender, age range and geographic origin. CONCLUSION: A simplified, sensitive, standardized, reproducible, and high-throughput assay was developed for the quantitation of NAbs against different Vaccinia strains. The current study provides useful insights for the future development of VTT-based vaccination in Beijing and Anhui provinces of China.",2012 Mar 16,"['Liu, Qiang', 'Huang, Weijin', 'Nie, Jianhui', 'Zhu, Rong', 'Gao, Dongying', 'Song, Aijing', 'Meng, Shufang', 'Xu, Xuemei', 'Wang, Youchun']",PLoS One,,,True
88a0b7d6447839c09069588d1761364ce9045d61,PMC,The occurrence of Chlamydia spp. in pigs with and without clinical disease,http://dx.doi.org/10.1186/1746-6148-8-9,PMC3307427,22280482,CC BY,"BACKGROUND: Within the genera Chlamydia, the development of refined diagnostic techniques has allowed the identification of four species that are capable of infecting pigs. The epidemiology, clinical, and zoonotic impacts of these species are however largely unknown. The study aimed to investigate the presence of Chlamydia spp. in the intestines of growing pigs and in conjunctival swabs from finisher pigs, and relate the findings to clinical signs. RESULTS: By histology, 20 of 48 pigs had intestinal lesions that may be consistent with chlamydial infection. By PCR, forty-six of the pigs were positive whereas two samples were inhibited. Sequencing of 19 DNA extracts identified these as Chlamydia suis. By immunohistochemistry, 32 of 44 samples were positive and a significant relationship was detected between macroscopically visible intestinal lesions and a high degree of infection. By real-time PCR, a significant difference was detected between pigs with and without conjunctivitis when a Ct value of 36 was employed but not when a Ct value of 38 was employed. CONCLUSIONS: Chlamydia suis was demonstrated in most samples and overall, no correlation to clinical signs was detected. However, a correlation was noted between samples with a high degree of infection and the presence of clinical signs. It is possible, that the intensive pig production systems studied might predispose for the transmission and maintenance of the infection thus increasing the infectious load and the risk for disease in the pig.",2012 Jan 26,"['Englund, Stina', 'Hård af Segerstad, Carl', 'Arnlund, Frida', 'Westergren, Eva', 'Jacobson, Magdalena']",BMC Vet Res,,,True
b85671451a6132068f92e5da9590cbc9ee5867d5,PMC,Suppression of Adenosine-Activated Chloride Transport by Ethanol in Airway Epithelia,http://dx.doi.org/10.1371/journal.pone.0032112,PMC3307712,22442662,CC BY,"Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM) for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (I(SC)) in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A(2B) adenosine receptor (A(2B)AR), largely abolished the adenosine-stimulated chloride transport, suggesting that A(2B)AR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A(2B)AR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections.",2012 Mar 19,"['Raju, Sammeta V.', 'Wang, Guoshun']",PLoS One,,,True
50fa3228f8067d61d3debffbe06c53deaf9dc863,PMC,Recombinant Vesicular Stomatitis Virus Vaccine Vectors Expressing Filovirus Glycoproteins Lack Neurovirulence in Nonhuman Primates,http://dx.doi.org/10.1371/journal.pntd.0001567,PMC3308941,22448291,CC0,"The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses an individual filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). The main concern with all replication-competent vaccines, including the rVSV filovirus GP vectors, is their safety. To address this concern, we performed a neurovirulence study using 21 cynomolgus macaques where the vaccines were administered intrathalamically. Seven animals received a rVSV vector expressing the Zaire ebolavirus (ZEBOV) GP; seven animals received a rVSV vector expressing the Lake Victoria marburgvirus (MARV) GP; three animals received rVSV-wild type (wt) vector, and four animals received vehicle control. Two of three animals given rVSV-wt showed severe neurological symptoms whereas animals receiving vehicle control, rVSV-ZEBOV-GP, or rVSV-MARV-GP did not develop these symptoms. Histological analysis revealed major lesions in neural tissues of all three rVSV-wt animals; however, no significant lesions were observed in any animals from the filovirus vaccine or vehicle control groups. These data strongly suggest that rVSV filovirus GP vaccine vectors lack the neurovirulence properties associated with the rVSV-wt parent vector and support their further development as a vaccine platform for human use.",2012 Mar 20,"['Mire, Chad E.', 'Miller, Andrew D.', 'Carville, Angela', 'Westmoreland, Susan V.', 'Geisbert, Joan B.', 'Mansfield, Keith G.', 'Feldmann, Heinz', 'Hensley, Lisa E.', 'Geisbert, Thomas W.']",PLoS Negl Trop Dis,,,True
af2a0da4beb166ca0b189ee6282120c9b664ea79,PMC,High Fidelity Processing and Activation of the Human α-Defensin HNP1 Precursor by Neutrophil Elastase and Proteinase 3,http://dx.doi.org/10.1371/journal.pone.0032469,PMC3308943,22448222,CC BY,"The azurophilic granules of human neutrophils contain four α-defensins called human neutrophil peptides (HNPs 1–4). HNPs are tridisulfide-linked antimicrobial peptides involved in the intracellular killing of organisms phagocytosed by neutrophils. The peptides are produced as inactive precursors (proHNPs) which are processed to active microbicides by as yet unidentified convertases. ProHNP1 was expressed in E. coli and the affinity-purified propeptide isolated as two species, one containing mature HNP1 sequence with native disulfide linkages (“folded proHNP1”) and the other containing non-native disulfide linked proHNP1 conformers (misfolded proHNP1). Native HNP1, liberated by CNBr treatment of folded proHNP1, was microbicidal against Staphylococcus aureus, but the peptide derived from misfolded proHNP1 was inactive. We hypothesized that neutrophil elastase (NE), proteinase 3 (PR3) or cathepsin G (CG), serine proteases that co-localize with HNPs in azurophil granules, are proHNP1 activating convertases. Folded proHNP1 was converted to mature HNP1 by both NE and PR3, but CG generated an HNP1 variant with an N-terminal dipeptide extension. NE and PR3 cleaved folded proHNP1 to produce a peptide indistinguishable from native HNP1 purified from neutrophils, and the microbicidal activities of in vitro derived and natural HNP1 peptides were equivalent. In contrast, misfolded proHNP1 conformers were degraded extensively under the same conditions. Thus, NE and PR3 possess proHNP1 convertase activity that requires the presence of the native HNP1 disulfide motif for high fidelity activation of the precursor in vitro.",2012 Mar 20,"['Tongaonkar, Prasad', 'Golji, Amir E.', 'Tran, Patti', 'Ouellette, André J.', 'Selsted, Michael E.']",PLoS One,,,True
9903fc2ee43aca54acf2469fdc2ae8de2e62a09c,PMC,Foxp3(+) Regulatory T Cells Control Persistence of Viral CNS Infection,http://dx.doi.org/10.1371/journal.pone.0033989,PMC3309005,22448284,CC BY,"We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified) mice and recombinant measles virus (MV). Using this model infection we investigated the role of regulatory T cells (Tregs) as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery. CD4(+) CD25(+) Foxp3(+) Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed. Virus-specific CD8(+) T cells predominantly recognising the H-2D(b)-presented viral hemagglutinin epitope MV-H(22–30) (RIVINREHL) were quantified in the brain by pentamer staining. Expansion of Tregs after intraperitoneal (i.p.) application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS. In contrast, depletion of Tregs using diphtheria toxin (DT) in DEREG (depletion of regulatory T cells)-mice induced an increase of virus-specific CD8(+) effector T cells in the brain and caused a reduction of the persistent infection. These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.",2012 Mar 20,"['Reuter, Dajana', 'Sparwasser, Tim', 'Hünig, Thomas', 'Schneider-Schaulies, Jürgen']",PLoS One,,,True
888a2dcee2c34b07d19a0528febb54aad70bdf00,PMC,Surveillance of Airborne Adenovirus and Mycoplasma pneumoniae in a Hospital Pediatric Department,http://dx.doi.org/10.1371/journal.pone.0033974,PMC3309934,22470502,CC BY,This investigation evaluated the distributions of airborne adenovirus and Mycoplasma pneumoniae in public areas in the pediatric department of Children's Hospital in northern Taiwan. The airborne viral and bacterial concentrations were evaluated twice a week for a year using filter sampling with an airflow rate of 12 liters per minute for eight hours in the pediatric outpatient department and 24 hours in the pediatric emergency room. Real-time polymerase chain reaction assays were conducted for analysis. Approximately 18% of the air samples from the pediatric emergency room were found to contain adenovirus. Approximately forty-six percent of the air samples from the pediatric outpatient department contained Mycoplasma pneumoniae DNA products. High detection rates of airborne adenovirus DNA were obtained in July and August in the pediatric public areas. Airborne Mycoplasma pneumoniae was detected only in July in the pediatric emergency room and the peak levels were found from August to January in the pediatric outpatient department. Airborne particles that contained adenovirus and Mycoplasma pneumoniae were the most prevalent in the pediatric public areas. The potential relationship between these airborne viral/bacterial particles and human infection should be examined further. Keywords: adenovirus; Mycoplasma pneumoniae; filter sampling; real-time polymerase chain reaction; hospital; pediatric public areas.,2012 Mar 21,"['Wan, Gwo-Hwa', 'Huang, Chung-Guei', 'Huang, Yhu-Chering', 'Huang, Ju-Ping', 'Yang, Su-Li', 'Lin, Tzou-Yien', 'Tsao, Kuo-Chien']",PLoS One,,,True
5fa62370245d4ad73220d6f42f8cb66064627aaa,PMC,Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells,http://dx.doi.org/10.1371/journal.ppat.1002584,PMC3310792,22457619,CC BY,"Dengue virus causes ∼50–100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.",2012 Mar 22,"['Perera, Rushika', 'Riley, Catherine', 'Isaac, Giorgis', 'Hopf-Jannasch, Amber S.', 'Moore, Ronald J.', 'Weitz, Karl W.', 'Pasa-Tolic, Ljiljana', 'Metz, Thomas O.', 'Adamec, Jiri', 'Kuhn, Richard J.']",PLoS Pathog,,,True
006bfa7dbe2caea917efd90843b0882c402abfce,PMC,Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells,http://dx.doi.org/10.1371/journal.ppat.1002584,PMC3310792,22457619,CC BY,"Dengue virus causes ∼50–100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.",2012 Mar 22,"['Perera, Rushika', 'Riley, Catherine', 'Isaac, Giorgis', 'Hopf-Jannasch, Amber S.', 'Moore, Ronald J.', 'Weitz, Karl W.', 'Pasa-Tolic, Ljiljana', 'Metz, Thomas O.', 'Adamec, Jiri', 'Kuhn, Richard J.']",PLoS Pathog,,,False
d2a7fc6bc3da9aee40450daa3b374b187dbd1948,PMC,Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells,http://dx.doi.org/10.1371/journal.ppat.1002584,PMC3310792,22457619,CC BY,"Dengue virus causes ∼50–100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.",2012 Mar 22,"['Perera, Rushika', 'Riley, Catherine', 'Isaac, Giorgis', 'Hopf-Jannasch, Amber S.', 'Moore, Ronald J.', 'Weitz, Karl W.', 'Pasa-Tolic, Ljiljana', 'Metz, Thomas O.', 'Adamec, Jiri', 'Kuhn, Richard J.']",PLoS Pathog,,,False
c334662c42a52cfaf8f1b3a8af1821230df9b798,PMC,Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells,http://dx.doi.org/10.1371/journal.ppat.1002584,PMC3310792,22457619,CC BY,"Dengue virus causes ∼50–100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.",2012 Mar 22,"['Perera, Rushika', 'Riley, Catherine', 'Isaac, Giorgis', 'Hopf-Jannasch, Amber S.', 'Moore, Ronald J.', 'Weitz, Karl W.', 'Pasa-Tolic, Ljiljana', 'Metz, Thomas O.', 'Adamec, Jiri', 'Kuhn, Richard J.']",PLoS Pathog,,,False
8dedaee19e09c9fd5a849dda12a4521ea675b1a4,PMC,Accidental Chlorine Gas Intoxication: Evaluation of 39 Patients,http://dx.doi.org/10.4021/jocmr2009.12.1283,PMC3311442,22481989,CC BY,"BACKGROUND: Chlorine is a known pulmonary irritant gas that may cause acute damage in the respiratory system. In this paper, the socio-demographic and clinical characteristics of 39 accidentally exposed patients to chlorine gas are reported and different emergency treatment modalities are also discussed. METHODS: Two emergency departments applications were retrospectively analyzed for evaluation of accidental chlorine gas exposure for year 2007. Patients were classified into 3 groups according to severity of clinical and laboratory findings based on the literature and duration of land of stay in the emergency department. The first group was slightly exposed (discharged within 6 hours), second group moderately exposed (treated and observed for 24 hours), and third group was severely exposed (hospitalized). Most of the patients were initially treated with a combination of humidified oxygen, corticosteroids, and bronchodilators. RESULTS: The average age was 17.03 ± 16.01 years (95% CI). Seven (17.9%) of them were female and 29 (74.4%) were children. Twenty-four patients (61.5%) were included in the first, nine (23.1%) were in second and six (15.4%) were in the third group. The presenting symptoms were cough, nausea, and vomiting and conjunctiva hyperemia for the first group, first groups symptoms plus dyspnea for the second group. Second groups symptoms plus palpitation, weakness and chest tightness were for the third group. Cough and dyspnea were seen in 64.1% and 30.8% of the patients respectively. No patients died. CONCLUSIONS: The authors recommend that non symptomatic or slightly exposed patients do not need any specific treatment or symptomatic treatment is sufficient. KEYWORDS: Accidental; Chlorine exposure; Chlorine gas; Chlorine intoxication; Emergency department",2009 Dec 28,"['Sever, Mustafa', 'Mordeniz, Cengiz', 'Sever, Fidan', 'Dokur, Mehmet']",J Clin Med Res,,,True
16ab54289da4d53548b4cf171a642e19fd81e660,PMC,Descriptive review and evaluation of the functioning of the International Health Regulations (IHR) Annex 2,http://dx.doi.org/10.1186/1744-8603-8-1,PMC3313850,22233652,CC BY,"BACKGROUND: The International Health Regulations (IHRs) (2005) was developed with the aim of governing international responses to public health risks and emergencies. The document requires all 194 World Health Organization (WHO) Member States to detect, assess, notify and report any potential public health emergency of international concern (PHEIC) under specific timelines. Annex 2 of the IHR outlines decision-making criteria for State-appointed National Focal Points (NFP) to report potential PHEICs to the WHO, and is a critical component to the effective functioning of the IHRs. METHODS: The aim of the study was to review and evaluate the functioning of Annex 2 across WHO-reporting States Parties. Specific objectives were to ascertain NFP awareness and knowledge of Annex 2, practical use of the tool, activities taken to implement it, its perceived usefulness and user-friendliness. Qualitative telephone interviews, followed by a quantitative online survey, were administered to NFPs between October, 2009 and February, 2010. RESULTS: A total of 29 and 133 NFPs participated in the qualitative and quantitative studies, respectively. Qualitative interviews found most NFPs had a strong working knowledge of Annex 2; perceived the tool to be relevant and useful for guiding decisions; and had institutionalized management, legislation and communication systems to support it. NFPs also perceived Annex 2 as human and disease-centric, and emphasized its reduced applicability to potential PHEICs involving bioterrorist attacks, infectious diseases among animals, radio-nuclear and chemical spills, and water- or food-borne contamination. Among quantitative survey respondents, 88% reported having excellent/good knowledge of Annex 2; 77% reported always/usually using Annex 2 for assessing potential PHEICs; 76% indicated their country had some legal, regulatory or administrative provisions for using Annex 2; 95% indicated Annex 2 was always/usually useful for facilitating decisions regarding notifiability of potential PHEICs. CONCLUSION: This evaluation, including a large sample of WHO-reporting States Parties, found that the IHR's Annex 2 is perceived as useful for guiding decisions about notifiability of potential PHEICs. There is scope for the WHO to expand training and guidance on application of the IHR's Annex 2 to specific contexts. Continued monitoring and evaluation of the functioning of the IHR is imperative to promoting global health security.",2012 Jan 10,"['Anema, Aranka', 'Druyts, Eric', 'Hollmeyer, Helge G', 'Hardiman, Maxwell C', 'Wilson, Kumanan']",Global Health,,,True
6a776cdff97d90eae72e7f8be666aef3a14224e2,PMC,Membrane Fusion and Cell Entry of XMRV Are pH-Independent and Modulated by the Envelope Glycoprotein's Cytoplasmic Tail,http://dx.doi.org/10.1371/journal.pone.0033734,PMC3313918,22479434,CC BY,"Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus that was originally identified from human prostate cancer patients and subsequently linked to chronic fatigue syndrome. Recent studies showed that XMRV is a recombinant mouse retrovirus; hence, its association with human diseases has become questionable. Here, we demonstrated that XMRV envelope (Env)-mediated pseudoviral infection is not blocked by lysosomotropic agents and cellular protease inhibitors, suggesting that XMRV entry is not pH-dependent. The full length XMRV Env was unable to induce syncytia formation and cell-cell fusion, even in cells overexpressing the viral receptor, XPR1. However, truncation of the C-terminal 21 or 33 amino acid residues in the cytoplasmic tail (CT) of XMRV Env induced substantial membrane fusion, not only in the permissive 293 cells but also in the nonpermissive CHO cells that lack a functional XPR1 receptor. The increased fusion activities of these truncations correlated with their enhanced SU shedding into culture media, suggesting conformational changes in the ectodomain of XMRV Env. Noticeably, further truncation of the CT of XMRV Env proximal to the membrane-spanning domain severely impaired the Env fusogenicity, as well as dramatically decreased the Env incorporations into MoMLV oncoretroviral and HIV-1 lentiviral vectors resulting in greatly reduced viral transductions. Collectively, our studies reveal that XMRV entry does not require a low pH or low pH-dependent host proteases, and that the cytoplasmic tail of XMRV Env critically modulates membrane fusion and cell entry. Our data also imply that additional cellular factors besides XPR1 are likely to be involved in XMRV entry.",2012 Mar 27,"['Côté, Marceline', 'Zheng, Yi-Min', 'Liu, Shan-Lu']",PLoS One,,,True
87795a5783981250b35b32635c37fd2a098c4ed6,PMC,"The Impact of Weather on Influenza and Pneumonia Mortality in New York City, 1975–2002: A Retrospective Study",http://dx.doi.org/10.1371/journal.pone.0034091,PMC3314701,22470518,CC BY,"The substantial winter influenza peak in temperate climates has lead to the hypothesis that cold and/or dry air is a causal factor in influenza variability. We examined the relationship between cold and/or dry air and daily influenza and pneumonia mortality in the cold season in the New York metropolitan area from 1975–2002. We conducted a retrospective study relating daily pneumonia and influenza mortality for New York City and surroundings from 1975–2002 to daily air temperature, dew point temperature (a measure of atmospheric humidity), and daily air mass type. We identified high mortality days and periods and employed temporal smoothers and lags to account for the latency period and the time between infection and death. Unpaired t-tests were used to compare high mortality events to non-events and nonparametric bootstrapped regression analysis was used to examine the characteristics of longer mortality episodes. We found a statistically significant (p = 0.003) association between periods of low dew point temperature and above normal pneumonia and influenza mortality 17 days later. The duration (r = −0.61) and severity (r = −0.56) of high mortality episodes was inversely correlated with morning dew point temperature prior to and during the episodes. Weeks in which moist polar air masses were common (air masses characterized by low dew point temperatures) were likewise followed by above normal mortality 17 days later (p = 0.019). This research supports the contention that cold, dry air may be related to influenza mortality and suggests that warning systems could provide enough lead time to be effective in mitigating the effects.",2012 Mar 28,"['Davis, Robert E.', 'Rossier, Colleen E.', 'Enfield, Kyle B.']",PLoS One,,,True
cf92667ce9f346dd79bc980fdb5d21a5cf6b334a,PMC,Emerging Viruses in the Felidae: Shifting Paradigms,http://dx.doi.org/10.3390/v4020236,PMC3315214,22470834,CC BY,"The domestic cat is afflicted with multiple viruses that serve as powerful models for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause these diseases have been studied for decades revealing detailed insight concerning transmission, virulence, origins and pathogenesis. Here we review recent genetic advances that have questioned traditional wisdom regarding the origins of virulent Feline infectious peritonitis (FIP) diseases, the pathogenic potential of Feline Immunodeficiency Virus (FIV) in wild non-domestic Felidae species, and the restriction of Feline Leukemia Virus (FeLV) mediated immune impairment to domestic cats rather than other Felidae species. The most recent interpretations indicate important new evolutionary conclusions implicating these deadly infectious agents in domestic and non-domestic felids.",2012 Feb 7,"['O’Brien, Stephen J.', 'Troyer, Jennifer L.', 'Brown, Meredith A.', 'Johnson, Warren E.', 'Antunes, Agostinho', 'Roelke, Melody E.', 'Pecon-Slattery, Jill']",Viruses,,,True
793ff384663ce5425d0b61619d47fb0b306d7ec1,PMC,Filovirus Entry: A Novelty in the Viral Fusion World,http://dx.doi.org/10.3390/v4020258,PMC3315215,22470835,CC BY,"Ebolavirus (EBOV) and Marburgvirus (MARV) that compose the filovirus family of negative strand RNA viruses infect a broad range of mammalian cells. Recent studies indicate that cellular entry of this family of viruses requires a series of cellular protein interactions and molecular mechanisms, some of which are unique to filoviruses and others are commonly used by all viral glycoproteins. Details of this entry pathway are highlighted here. Virus entry into cells is initiated by the interaction of the viral glycoprotein(1) subunit (GP(1)) with both adherence factors and one or more receptors on the surface of host cells. On epithelial cells, we recently demonstrated that TIM-1 serves as a receptor for this family of viruses, but the cell surface receptors in other cell types remain unidentified. Upon receptor binding, the virus is internalized into endosomes primarily via macropinocytosis, but perhaps by other mechanisms as well. Within the acidified endosome, the heavily glycosylated GP(1) is cleaved to a smaller form by the low pH-dependent cellular proteases Cathepsin L and B, exposing residues in the receptor binding site (RBS). Details of the molecular events following cathepsin-dependent trimming of GP(1) are currently incomplete; however, the processed GP(1) specifically interacts with endosomal/lysosomal membranes that contain the Niemann Pick C1 (NPC1) protein and expression of NPC1 is required for productive infection, suggesting that GP/NPC1 interactions may be an important late step in the entry process. Additional events such as further GP(1) processing and/or reducing events may also be required to generate a fusion-ready form of the glycoprotein. Once this has been achieved, sequences in the filovirus GP(2) subunit mediate viral/cellular membrane fusion via mechanisms similar to those previously described for other enveloped viruses. This multi-step entry pathway highlights the complex and highly orchestrated path of internalization and fusion that appears unique for filoviruses.",2012 Feb 7,"['Hunt, Catherine L.', 'Lennemann, Nicholas J.', 'Maury, Wendy']",Viruses,,,True
bcdceb50d70afda0d8615859b356484af61aab04,PMC,"Specific, simple and rapid detection of porcine circovirus type 2 using the loop-mediated isothermal amplification method",http://dx.doi.org/10.1186/1743-422X-8-126,PMC3315793,21414233,CC BY,"BACKGROUND: Porcine circovirus type 2 (PCV2) is the causative agent of postweaning multisystemic wasting syndrome (PMWS), and porcine dermatitis and nephropathy syndrome (PDNS). It has caused heavy losses in global agriculture in recent decades. Rapid detection of PCV2 is very important for the effective prophylaxis and treatment of PMWS. RESULTS: A loop-mediated isothermal amplification (LAMP) assay was used to detect PCV2 in this study. Three pairs of primers were specially designed for recognizing eight distinct sequences of the ORF2 gene. This gene lies in the PCV2 virus genome sequence, and encodes the Rep protein that is involved in virus replication. Time and temperature conditions for amplification of PCV2 genes were optimized to be 55 min at 59°C. The analysis of clinical samples indicated that the LAMP method was highly sensitive. The detection limit for PCV2 by the LAMP assay was 10 copies, whereas the limit by conventional PCR was 1000 copies. The assay did not cross-react with PCV1, porcine reproductive and respiratory syndrome virus, porcine epidemic diarrhea virus, transmissible gastroenteritis of pigs virus or rotavirus. When 110 samples were tested using the established LAMP system, 95 were detected as positive. CONCLUSION: The newly developed LAMP detection method for PCV2 was more specific, sensitive, rapid and simple than before. It complements and extends previous methods for PCV2 detection and provides an alternative approach for detection of PCV2.",2011 Mar 18,"['Zhao, Kai', 'Shi, Wei', 'Han, Fangting', 'Xu, Yan', 'Zhu, Lianlong', 'Zou, Yong', 'Wu, Xiao', 'Zhu, Hong', 'Tan, Furong', 'Tao, Shiru', 'Tang, Xueming']",Virol J,,,True
3ed400293b6f0963dcffb081e94de5229fb42cc7,PMC,IFITM Proteins Restrict Antibody-Dependent Enhancement of Dengue Virus Infection,http://dx.doi.org/10.1371/journal.pone.0034508,PMC3316688,22479637,CC BY,"Interferon-inducible transmembrane (IFITM) proteins restrict the entry processes of several pathogenic viruses, including the flaviviruses West Nile virus and dengue virus (DENV). DENV infects cells directly or via antibody-dependent enhancement (ADE) in Fc-receptor-bearing cells, a process thought to contribute to severe disease in a secondary infection. Here we investigated whether ADE-mediated DENV infection bypasses IFITM-mediated restriction or whether IFITM proteins can be protective in a secondary infection. We observed that IFITM proteins restricted ADE-mediated and direct infection with comparable efficiencies in a myelogenous leukemia cell line. Our data suggest that IFITM proteins can contribute to control of secondary DENV infections.",2012 Mar 30,"['Chan, Ying Kai', 'Huang, I-Chueh', 'Farzan, Michael']",PLoS One,,,True
ae072e0f04db143d038aa090e714f31e0c8c34bc,PMC,High Viral Load of Human Bocavirus Correlates with Duration of Wheezing in Children with Severe Lower Respiratory Tract Infection,http://dx.doi.org/10.1371/journal.pone.0034353,PMC3316689,22479609,CC BY,"BACKGROUND: Human bocavirus (HBoV) is a newly discovered parvovirus and increasing evidences are available to support its role as an etiologic agent in lower respiratory tract infection (LRTI). The objective of this study is to assess the impact of HBoV viral load on clinical characteristics in children who were HBoV positive and suffered severe LRTI. METHODS: Lower respiratory tract aspirates from 186 hospitalized children with severe LRTI were obtained by bronchoscopy. HBoVs were detected by real-time PCR and other 10 infectious agents were examined using PCR and/or direct fluorescent assay. RESULTS: Thirty-one patients (24.6%) were tested positive for HBoV in the respiratory tract aspirates. Fifteen samples had a high viral load (>10(4) copies/mL) and the other sixteen samples had a low viral load (<10(4) copies/mL). The duration of presented wheezing and hospitalization was longer in children with high viral load of HBoV than that in children with low viral load. The days of wheezing showed a correlation with viral load of HBoV. CONCLUSION: We confirmed that HBoV was frequently detected in patients with severe LRTI. Wheezing was one of the most common symptoms presented by patients with positive HBoV. A high HBoV viral load could be an etiologic agent for LRTI, which led to more severe lower respiratory tract symptom, longer duration of wheezing and hospitalization.",2012 Mar 30,"['Deng, Yu', 'Gu, Xiaoyang', 'Zhao, Xiaodong', 'Luo, Jian', 'Luo, Zhengxiu', 'Wang, Lijia', 'Fu, Zhou', 'Yang, Xiqiang', 'Liu, Enmei']",PLoS One,,,True
8ed0914312a47f0d8c127bc1db47446c1792e1de,PMC,Public health interventions for epidemics: implications for multiple infection waves,http://dx.doi.org/10.1186/1471-2458-11-S1-S2,PMC3317576,21356131,CC BY,"BACKGROUND: Epidemics with multiple infection waves have been documented for some human diseases, most notably during past influenza pandemics. While pathogen evolution, co-infection, and behavioural changes have been proposed as possible mechanisms for the occurrence of subsequent outbreaks, the effect of public health interventions remains undetermined. METHODS: We develop mean-field and stochastic epidemiological models for disease transmission, and perform simulations to show how control measures, such as drug treatment and isolation of ill individuals, can influence the epidemic profile and generate sequences of infection waves with different characteristics. RESULTS: We demonstrate the impact of parameters representing the effectiveness and adverse consequences of intervention measures, such as treatment and emergence of drug resistance, on the spread of a pathogen in the population. If pathogen resistant strains evolve under drug pressure, multiple outbreaks are possible with variability in their characteristics, magnitude, and timing. In this context, the level of drug use and isolation capacity play an important role in the occurrence of subsequent outbreaks. Our simulations for influenza infection as a case study indicate that the intensive use of these interventions during the early stages of the epidemic could delay the spread of disease, but it may also result in later infection waves with possibly larger magnitudes. CONCLUSIONS: The findings highlight the importance of intervention parameters in the process of public health decision-making, and in evaluating control measures when facing substantial uncertainty regarding the epidemiological characteristics of an emerging infectious pathogen. Critical factors that influence population health including evolutionary responses of the pathogen under the pressure of different intervention measures during an epidemic should be considered for the design of effective strategies that address short-term targets compatible with long-term disease outcomes.",2011 Feb 25,"['Wessel, Lindsay', 'Hua, Yi', 'Wu, Jianhong', 'Moghadas, Seyed M']",BMC Public Health,,,True
aae9028bc39c23fd877b0059777933774b7bf2e0,PMC,Increasing the X-ray Diffraction Power of Protein Crystals by Dehydration: The Case of Bovine Serum Albumin and a Survey of Literature Data,http://dx.doi.org/10.3390/ijms13033782,PMC3317743,22489183,CC BY,"Serum albumin is one of the most widely studied proteins. It is the most abundant protein in plasma with a typical concentration of 5 g/100 mL and the principal transporter of fatty acids in plasma. While the crystal structures of human serum albumin (HSA) free and in complex with fatty acids, hemin, and local anesthetics have been characterized, no crystallographic models are available on bovine serum albumin (BSA), presumably because of the poor diffraction power of existing hexagonal BSA crystals. Here, the crystallization and diffraction data of a new BSA crystal form, obtained by the hanging drop method using MPEG 5K as precipitating agent, are presented. The crystals belong to space group C2, with unit-cell parameters a = 216.45 Å, b = 44.72 Å, c = 140.18 Å, β = 114.5°. Dehydration was found to increase the diffraction limit of BSA crystals from ~8 Å to 3.2 Å, probably by improving the packing of protein molecules in the crystal lattice. These results, together with a survey of more than 60 successful cases of protein crystal dehydration, confirm that it can be a useful procedure to be used in initial screening as a method of improving the diffraction limits of existing crystals.",2012 Mar 21,"['Krauss, Irene Russo', 'Sica, Filomena', 'Mattia, Carlo Andrea', 'Merlino, Antonello']",Int J Mol Sci,,,True
0241ada1b12eaacadc56a59586bc1728a580583d,PMC,Permissiveness of human hepatoma cell lines for HCV infection,http://dx.doi.org/10.1186/1743-422X-9-30,PMC3317838,22273112,CC BY,"BACKGROUND: Although primary and established human hepatoma cell lines have been evaluated for hepatitis C virus (HCV) infection in vitro, thus far only Huh7 cells have been found to be highly permissive for infectious HCV. Since our understanding of the HCV lifecycle would benefit from the identification of additional permissive cell lines, we assembled a panel of hepatic and non-hepatic cell lines and assessed their ability to support HCV infection. Here we show infection of the human hepatoma cell lines PLC/PRF/5 and Hep3B with cell culture-derived HCV (HCVcc), albeit to lower levels than that achieved in Huh7 cells. To better understand the reduced permissiveness of PLC and Hep3B cells for HCVcc infection, we performed studies to evaluate the ability of each cell line to support specific steps of the viral lifecycle (i.e. entry, replication, egress and spread). RESULTS: We found that while the early events in HCV infection (i.e. entry plus replication initiation) are cumulatively equivalent or only marginally reduced in PLC and Hep3B cells, later steps of the viral life cycle such as steady-state replication, de novo virus production and/or spread are impaired to different degrees in PLC and Hep3B cultures compared to Huh7 cell cultures. Interestingly, we also observed that interferon stimulated gene (i.e. ISG56) expression was significantly and differentially up-regulated in PLC and Hep3B cells following viral infection. CONCLUSIONS: We conclude that the restrictions observed later during HCV infection in these cell lines could in part be attributed to HCV-induced innate signaling. Nevertheless, the identification of two new cell lines capable of supporting authentic HCVcc infection, even at reduced levels, expands the current repertoire of cell lines amendable for the study of HCV in vitro and should aid in further elucidating HCV biology and the cellular determinants that modulate HCV infection.",2012 Jan 24,"['Sainz, Bruno', 'Barretto, Naina', 'Yu, Xuemei', 'Corcoran, Peter', 'Uprichard, Susan L']",Virol J,,,True
454a87f362323152fc47fe4593afc755422f1e7b,PMC,Detection of Mycobacterium ulcerans by the Loop Mediated Isothermal Amplification Method,http://dx.doi.org/10.1371/journal.pntd.0001590,PMC3317900,22509415,CC BY,"BACKGROUND: Buruli ulcer (BU) caused by Mycobacterium ulcerans (M. ulcerans) has emerged as an important public health problem in several rural communities in sub-Saharan Africa. Early diagnosis and prompt treatment are important in preventing disfiguring complications associated with late stages of the disease progression. Presently there is no simple and rapid test that is appropriate for early diagnosis and use in the low-resource settings where M. ulcerans is most prevalent. METHODOLOGY: We compared conventional and pocket warmer loop mediated isothermal amplification (LAMP) methods (using a heat block and a pocket warmer respectively as heat source for amplification reaction) for the detection of M. ulcerans in clinical specimens. The effect of purified and crude DNA preparations on the detection rate of the LAMP assays were also investigated and compared with that of IS2404 PCR, a reference assay for the detection of M. ulcerans. Thirty clinical specimens from suspected BU cases were examined by LAMP and IS2404 PCR. PRINCIPAL FINDINGS: The lower detection limit of both LAMP methods at 60°C was 300 copies of IS2404 and 30 copies of IS2404 for the conventional LAMP at 65°C. When purified DNA extracts were used, both the conventional LAMP and IS2404 PCR concordantly detected 21 positive cases, while the pocket warmer LAMP detected 19 cases. Nine of 30 samples were positive by both the LAMP assays as well as IS2404 PCR when crude extracts of clinical specimens were used. CONCLUSION/SIGNIFICANCE: The LAMP method can be used as a simple and rapid test for the detection of M. ulcerans in clinical specimens. However, obtaining purified DNA, as well as generating isothermal conditions, remains a major challenge for the use of the LAMP method under field conditions. With further improvement in DNA extraction and amplification conditions, the pwLAMP could be used as a point of care diagnostic test for BU",2012 Apr 3,"['Ablordey, Anthony', 'Amissah, Diana Ackon', 'Aboagye, Isaac Frimpong', 'Hatano, Ben', 'Yamazaki, Toshio', 'Sata, Tetsutaro', 'Ishikawa, Koichi', 'Katano, Harutaka']",PLoS Negl Trop Dis,,,True
51a9f0de2c657fd582c5ff023027833d48e4876b,PMC,A Human PrM Antibody That Recognizes a Novel Cryptic Epitope on Dengue E Glycoprotein,http://dx.doi.org/10.1371/journal.pone.0033451,PMC3317930,22509258,CC BY,"Dengue virus (DENV) is a major mosquito-borne pathogen infecting up to 100 million people each year; so far no effective treatment or vaccines are available. Recently, highly cross-reactive and infection-enhancing pre-membrane (prM)-specific antibodies were found to dominate the anti-DENV immune response in humans, raising concern over vaccine candidates that contain native dengue prM sequences. In this study, we have isolated a broadly cross-reactive prM-specific antibody, D29, during a screen with a non-immunized human Fab-phage library against the four serotypes of DENV. The antibody is capable of restoring the infectivity of virtually non-infectious immature DENV (imDENV) in FcγR-bearing K562 cells. Remarkably, D29 also cross-reacted with a cryptic epitope on the envelope (E) protein located to the DI/DII junction as evidenced by site-directed mutagenesis. This cryptic epitope, while inaccessible to antibody binding in a native virus particle, may become exposed if E is not properly folded. These findings suggest that generation of anti-prM antibodies that enhance DENV infection may not be completely avoided even with immunization strategies employing E protein alone or subunits of E proteins.",2012 Apr 3,"['Chan, Annie Hoi Yi', 'Tan, Hwee Cheng', 'Chow, Angelia Yee', 'Lim, Angeline Pei Chiew', 'Lok, Shee Mei', 'Moreland, Nicole J.', 'Vasudevan, Subhash G.', 'MacAry, Paul A.', 'Ooi, Eng Eong', 'Hanson, Brendon J.']",PLoS One,,,True
6b51562f63de5739f2b7ebf5f9c34365ac6ee545,PMC,A Non-VH1-69 Heterosubtypic Neutralizing Human Monoclonal Antibody Protects Mice against H1N1 and H5N1 Viruses,http://dx.doi.org/10.1371/journal.pone.0034415,PMC3319592,22496802,CC0,"Influenza viruses are among the most important human pathogens and are responsible for annual epidemics and sporadic, potentially devastating pandemics. The humoral immune response plays an important role in the defense against these viruses, providing protection mainly by producing antibodies directed against the hemagglutinin (HA) glycoprotein. However, their high genetic variability allows the virus to evade the host immune response and the potential protection offered by seasonal vaccines. The emergence of resistance to antiviral drugs in recent years further limits the options available for the control of influenza. The development of alternative strategies for influenza prophylaxis and therapy is therefore urgently needed. In this study, we describe a human monoclonal antibody (PN-SIA49) that recognizes a highly conserved epitope located on the stem region of the HA and able to neutralize a broad spectrum of influenza viruses belonging to different subtypes (H1, H2 and H5). Furthermore, we describe its protective activity in mice after lethal challenge with H1N1 and H5N1 viruses suggesting a potential application in the treatment of influenza virus infections.",2012 Apr 4,"['De Marco, Donata', 'Clementi, Nicola', 'Mancini, Nicasio', 'Solforosi, Laura', 'Moreno, Guisella J.', 'Sun, Xiangjie', 'Tumpey, Terrence M.', 'Gubareva, Larisa V.', 'Mishin, Vasiliy', 'Clementi, Massimo', 'Burioni, Roberto']",PLoS One,,,True
1fbbc167a21646cce197832a514a0877f0846fb4,PMC,A Non-VH1-69 Heterosubtypic Neutralizing Human Monoclonal Antibody Protects Mice against H1N1 and H5N1 Viruses,http://dx.doi.org/10.1371/journal.pone.0034415,PMC3319592,22496802,CC0,"Influenza viruses are among the most important human pathogens and are responsible for annual epidemics and sporadic, potentially devastating pandemics. The humoral immune response plays an important role in the defense against these viruses, providing protection mainly by producing antibodies directed against the hemagglutinin (HA) glycoprotein. However, their high genetic variability allows the virus to evade the host immune response and the potential protection offered by seasonal vaccines. The emergence of resistance to antiviral drugs in recent years further limits the options available for the control of influenza. The development of alternative strategies for influenza prophylaxis and therapy is therefore urgently needed. In this study, we describe a human monoclonal antibody (PN-SIA49) that recognizes a highly conserved epitope located on the stem region of the HA and able to neutralize a broad spectrum of influenza viruses belonging to different subtypes (H1, H2 and H5). Furthermore, we describe its protective activity in mice after lethal challenge with H1N1 and H5N1 viruses suggesting a potential application in the treatment of influenza virus infections.",2012 Apr 4,"['De Marco, Donata', 'Clementi, Nicola', 'Mancini, Nicasio', 'Solforosi, Laura', 'Moreno, Guisella J.', 'Sun, Xiangjie', 'Tumpey, Terrence M.', 'Gubareva, Larisa V.', 'Mishin, Vasiliy', 'Clementi, Massimo', 'Burioni, Roberto']",PLoS One,,,False
dda03cf2660471cfbde21ca13001cfe145c8801b,PMC,A Non-VH1-69 Heterosubtypic Neutralizing Human Monoclonal Antibody Protects Mice against H1N1 and H5N1 Viruses,http://dx.doi.org/10.1371/journal.pone.0034415,PMC3319592,22496802,CC0,"Influenza viruses are among the most important human pathogens and are responsible for annual epidemics and sporadic, potentially devastating pandemics. The humoral immune response plays an important role in the defense against these viruses, providing protection mainly by producing antibodies directed against the hemagglutinin (HA) glycoprotein. However, their high genetic variability allows the virus to evade the host immune response and the potential protection offered by seasonal vaccines. The emergence of resistance to antiviral drugs in recent years further limits the options available for the control of influenza. The development of alternative strategies for influenza prophylaxis and therapy is therefore urgently needed. In this study, we describe a human monoclonal antibody (PN-SIA49) that recognizes a highly conserved epitope located on the stem region of the HA and able to neutralize a broad spectrum of influenza viruses belonging to different subtypes (H1, H2 and H5). Furthermore, we describe its protective activity in mice after lethal challenge with H1N1 and H5N1 viruses suggesting a potential application in the treatment of influenza virus infections.",2012 Apr 4,"['De Marco, Donata', 'Clementi, Nicola', 'Mancini, Nicasio', 'Solforosi, Laura', 'Moreno, Guisella J.', 'Sun, Xiangjie', 'Tumpey, Terrence M.', 'Gubareva, Larisa V.', 'Mishin, Vasiliy', 'Clementi, Massimo', 'Burioni, Roberto']",PLoS One,,,False
2ab8cb240c2f488f5a7bbcf117239eed7e3b9633,PMC,A Non-VH1-69 Heterosubtypic Neutralizing Human Monoclonal Antibody Protects Mice against H1N1 and H5N1 Viruses,http://dx.doi.org/10.1371/journal.pone.0034415,PMC3319592,22496802,CC0,"Influenza viruses are among the most important human pathogens and are responsible for annual epidemics and sporadic, potentially devastating pandemics. The humoral immune response plays an important role in the defense against these viruses, providing protection mainly by producing antibodies directed against the hemagglutinin (HA) glycoprotein. However, their high genetic variability allows the virus to evade the host immune response and the potential protection offered by seasonal vaccines. The emergence of resistance to antiviral drugs in recent years further limits the options available for the control of influenza. The development of alternative strategies for influenza prophylaxis and therapy is therefore urgently needed. In this study, we describe a human monoclonal antibody (PN-SIA49) that recognizes a highly conserved epitope located on the stem region of the HA and able to neutralize a broad spectrum of influenza viruses belonging to different subtypes (H1, H2 and H5). Furthermore, we describe its protective activity in mice after lethal challenge with H1N1 and H5N1 viruses suggesting a potential application in the treatment of influenza virus infections.",2012 Apr 4,"['De Marco, Donata', 'Clementi, Nicola', 'Mancini, Nicasio', 'Solforosi, Laura', 'Moreno, Guisella J.', 'Sun, Xiangjie', 'Tumpey, Terrence M.', 'Gubareva, Larisa V.', 'Mishin, Vasiliy', 'Clementi, Massimo', 'Burioni, Roberto']",PLoS One,,,False
9575b82e4a705536bb73124514fa77255c3467c2,PMC,A Non-VH1-69 Heterosubtypic Neutralizing Human Monoclonal Antibody Protects Mice against H1N1 and H5N1 Viruses,http://dx.doi.org/10.1371/journal.pone.0034415,PMC3319592,22496802,CC0,"Influenza viruses are among the most important human pathogens and are responsible for annual epidemics and sporadic, potentially devastating pandemics. The humoral immune response plays an important role in the defense against these viruses, providing protection mainly by producing antibodies directed against the hemagglutinin (HA) glycoprotein. However, their high genetic variability allows the virus to evade the host immune response and the potential protection offered by seasonal vaccines. The emergence of resistance to antiviral drugs in recent years further limits the options available for the control of influenza. The development of alternative strategies for influenza prophylaxis and therapy is therefore urgently needed. In this study, we describe a human monoclonal antibody (PN-SIA49) that recognizes a highly conserved epitope located on the stem region of the HA and able to neutralize a broad spectrum of influenza viruses belonging to different subtypes (H1, H2 and H5). Furthermore, we describe its protective activity in mice after lethal challenge with H1N1 and H5N1 viruses suggesting a potential application in the treatment of influenza virus infections.",2012 Apr 4,"['De Marco, Donata', 'Clementi, Nicola', 'Mancini, Nicasio', 'Solforosi, Laura', 'Moreno, Guisella J.', 'Sun, Xiangjie', 'Tumpey, Terrence M.', 'Gubareva, Larisa V.', 'Mishin, Vasiliy', 'Clementi, Massimo', 'Burioni, Roberto']",PLoS One,,,False
7b4b3759cdde4218ea23a081b386bcffd7e6afc6,PMC,A Family-Wide RT-PCR Assay for Detection of Paramyxoviruses and Application to a Large-Scale Surveillance Study,http://dx.doi.org/10.1371/journal.pone.0034961,PMC3319594,22496880,CC BY,"Family-wide molecular diagnostic assays are valuable tools for initial identification of viruses during outbreaks and to limit costs of surveillance studies. Recent discoveries of paramyxoviruses have called for such assay that is able to detect all known and unknown paramyxoviruses in one round of PCR amplification. We have developed a RT-PCR assay consisting of a single degenerate primer set, able to detect all members of the Paramyxoviridae family including all virus genera within the subfamilies Paramyxovirinae and Pneumovirinae. Primers anneal to domain III of the polymerase gene, with the 3′ end of the reverse primer annealing to the conserved motif GDNQ, which is proposed to be the active site for nucleotide polymerization. The assay was fully optimized and was shown to indeed detect all available paramyxoviruses tested. Clinical specimens from hospitalized patients that tested positive for known paramyxoviruses in conventional assays were also detected with the novel family-wide test. A high-throughput fluorescence-based RT-PCR version of the assay was developed for screening large numbers of specimens. A large number of samples collected from wild birds was tested, resulting in the detection of avian paramyxoviruses type 1 in both barnacle and white-fronted geese, and type 8 in barnacle geese. Avian metapneumovirus type C was found for the first time in Europe in mallards, greylag geese and common gulls. The single round family-wide RT-PCR assay described here is a useful tool for the detection of known and unknown paramyxoviruses, and screening of large sample collections from humans and animals.",2012 Apr 4,"['van Boheemen, Sander', 'Bestebroer, Theo M.', 'Verhagen, Josanne H.', 'Osterhaus, Albert D. M. E.', 'Pas, Suzan D.', 'Herfst, Sander', 'Fouchier, Ron A. M.']",PLoS One,,,True
0b9b177210a4b23ff4745f2717083ba047a9e770,PMC,Systematic Identification of Spontaneous Preterm Birth-Associated RNA Transcripts in Maternal Plasma,http://dx.doi.org/10.1371/journal.pone.0034328,PMC3320630,22496790,CC BY,"BACKGROUND: Spontaneous preterm birth (SPB, before 37 gestational weeks) is a major cause of perinatal mortality and morbidity, but its pathogenesis remains unclear. Studies on SPB have been hampered by the limited availability of markers for SPB in predelivery clinical samples that can be easily compared with gestational age-matched normal controls. We hypothesize that SPB involves aberrant placental RNA expression, and that such RNA transcripts can be detected in predelivery maternal plasma samples, which can be compared with gestational age-matched controls. PRINCIPAL FINDINGS: Using gene expression microarray to profile essentially all human genes, we observed that 426 probe signals were changed by >2.9-fold in the SPB placentas, compared with the spontaneous term birth (STB) placentas. Among the genes represented by those probes, we observed an over-representation of functions in RNA stabilization, extracellular matrix binding, and acute inflammatory response. Using RT-quantitative PCR, we observed differences in the RNA concentrations of certain genes only between the SPB and STB placentas, but not between the STB and term elective cesarean delivery placentas. Notably, 36 RNA transcripts were observed at placental microarray signals higher than a threshold, which indicated the possibility of their detection in maternal plasma. Among them, the IL1RL1 mRNA was tested in plasma samples taken from 37 women. It was detected in 6 of 10 (60%) plasma samples collected during the presentation of preterm labor (≤32.9 weeks) in women eventually giving SPB, but was detected in only 1 of 27 (4%) samples collected during matched gestational weeks from women with no preterm labor (Fisher exact test, p = 0.00056). CONCLUSION: We have identified 36 SPB-associated RNA transcripts, which are possibly detectable in maternal plasma. We have illustrated that the IL1RL1 mRNA was more frequently detected in predelivery maternal plasma samples collected from women resulting in SPB than the gestational-age matched controls.",2012 Apr 5,"['Chim, Stephen S. C.', 'Lee, Wing S.', 'Ting, Yuen H.', 'Chan, Oi K.', 'Lee, Shara W. Y.', 'Leung, Tak Y.']",PLoS One,,,True
23f5f98892b12255b20f4b0a0ec1f3e7b29d5d72,PMC,Angiotensin-Converting Enzyme 2 (ACE2) Is a Key Modulator of the Renin Angiotensin System in Health and Disease,http://dx.doi.org/10.1155/2012/256294,PMC3321295,22536270,CC BY,"Angiotensin-converting enzyme 2 (ACE2) shares some homology with angiotensin-converting enzyme (ACE) but is not inhibited by ACE inhibitors. The main role of ACE2 is the degradation of Ang II resulting in the formation of angiotensin 1–7 (Ang 1–7) which opposes the actions of Ang II. Increased Ang II levels are thought to upregulate ACE2 activity, and in ACE2 deficient mice Ang II levels are approximately double that of wild-type mice, whilst Ang 1–7 levels are almost undetectable. Thus, ACE2 plays a crucial role in the RAS because it opposes the actions of Ang II. Consequently, it has a beneficial role in many diseases such as hypertension, diabetes, and cardiovascular disease where its expression is decreased. Not surprisingly, current therapeutic strategies for ACE2 involve augmenting its expression using ACE2 adenoviruses, recombinant ACE2 or compounds in these diseases thereby affording some organ protection.",2012 Mar 20,"['Tikellis, Chris', 'Thomas, M. C.']",Int J Pept,,,True
084f1464fd6c0885f64af9c09c1460ef50dddd01,PMC,Revealing −1 Programmed Ribosomal Frameshifting Mechanisms by Single-Molecule Techniques and Computational Methods,http://dx.doi.org/10.1155/2012/569870,PMC3321566,22545064,CC BY,"Programmed ribosomal frameshifting (PRF) serves as an intrinsic translational regulation mechanism employed by some viruses to control the ratio between structural and enzymatic proteins. Most viral mRNAs which use PRF adapt an H-type pseudoknot to stimulate −1 PRF. The relationship between the thermodynamic stability and the frameshifting efficiency of pseudoknots has not been fully understood. Recently, single-molecule force spectroscopy has revealed that the frequency of −1 PRF correlates with the unwinding forces required for disrupting pseudoknots, and that some of the unwinding work dissipates irreversibly due to the torsional restraint of pseudoknots. Complementary to single-molecule techniques, computational modeling provides insights into global motions of the ribosome, whose structural transitions during frameshifting have not yet been elucidated in atomic detail. Taken together, recent advances in biophysical tools may help to develop antiviral therapies that target the ubiquitous −1 PRF mechanism among viruses.",2012 Apr 1,"Chang, Kai-Chun",Comput Math Methods Med,,,True
6ea0187c80591fcbe19d37343f9957859753b129,PMC,Human Cytomegalovirus Entry into Dendritic Cells Occurs via a Macropinocytosis-Like Pathway in a pH-Independent and Cholesterol-Dependent Manner,http://dx.doi.org/10.1371/journal.pone.0034795,PMC3322158,22496863,CC BY,"Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that is able to infect fibroblastic, epithelial, endothelial and hematopoietic cells. Over the past ten years, several groups have provided direct evidence that dendritic cells (DCs) fully support the HCMV lytic cycle. We previously demonstrated that the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) has a prominent role in the docking of HCMV on monocyte-derived DCs (MDDCs). The DC-SIGN/HCMV interaction was demonstrated to be a crucial and early event that substantially enhanced infection in trans, i.e., from one CMV-bearing cell to another non-infected cell (or trans-infection), and rendered susceptible cells fully permissive to HCMV infection. Nevertheless, nothing is yet known about how HCMV enters MDDCs. In this study, we demonstrated that VHL/E HCMV virions (an endothelio/dendrotropic strain) are first internalized into MDDCs by a macropinocytosis-like process in an actin- and cholesterol-dependent, but pH-independent, manner. We observed the accumulation of virions in large uncoated vesicles with endosomal features, and the virions remained as intact particles that retained infectious potential for several hours. This trans-infection property was specific to MDDCs because monocyte-derived macrophages or monocytes from the same donor were unable to allow the accumulation of and the subsequent transmission of the virus. Together, these data allowed us to delineate the early mechanisms of the internalization and entry of an endothelio/dendrotropic HCMV strain into human MDDCs and to propose that DCs can serve as a ""Trojan horse"" to convey CMV from entry sites to other locations that may favor the occurrence of either latency or acute infection.",2012 Apr 9,"['Haspot, Fabienne', 'Lavault, Amélie', 'Sinzger, Christian', 'Laib Sampaio, Kerstin', 'Stierhof, York-Dieter', 'Pilet, Paul', 'Bressolette-Bodin, Céline', 'Halary, Franck']",PLoS One,,,True
24ed22a878649ce74463bf63090563093d002c86,PMC,Exposure to Ozone Modulates Human Airway Protease/Antiprotease Balance Contributing to Increased Influenza A Infection,http://dx.doi.org/10.1371/journal.pone.0035108,PMC3322171,22496898,CC BY,"Exposure to oxidant air pollution is associated with increased respiratory morbidities and susceptibility to infections. Ozone is a commonly encountered oxidant air pollutant, yet its effects on influenza infections in humans are not known. The greater Mexico City area was the primary site for the spring 2009 influenza A H1N1 pandemic, which also coincided with high levels of environmental ozone. Proteolytic cleavage of the viral membrane protein hemagglutinin (HA) is essential for influenza virus infectivity. Recent studies suggest that HA cleavage might be cell-associated and facilitated by the type II transmembrane serine proteases (TTSPs) human airway trypsin-like protease (HAT) and transmembrane protease, serine 2 (TMPRSS2), whose activities are regulated by antiproteases, such as secretory leukocyte protease inhibitor (SLPI). Based on these observations, we sought to determine how acute exposure to ozone may modulate cellular protease/antiprotease expression and function, and to define their roles in a viral infection. We utilized our in vitro model of differentiated human nasal epithelial cells (NECs) to determine the effects of ozone on influenza cleavage, entry, and replication. We show that ozone exposure disrupts the protease/antiprotease balance within the airway liquid. We also determined that functional forms of HAT, TMPRSS2, and SLPI are secreted from human airway epithelium, and acute exposure to ozone inversely alters their expression levels. We also show that addition of antioxidants significantly reduces virus replication through the induction of SLPI. In addition, we determined that ozone-induced cleavage of the viral HA protein is not cell-associated and that secreted endogenous proteases are sufficient to activate HA leading to a significant increase in viral replication. Our data indicate that pre-exposure to ozone disrupts the protease/antiprotease balance found in the human airway, leading to increased influenza susceptibility.",2012 Apr 9,"['Kesic, Matthew J.', 'Meyer, Megan', 'Bauer, Rebecca', 'Jaspers, Ilona']",PLoS One,,,True
5e01fabcf9b38073be541d0ac1c9f147c99a7af7,PMC,Predicting RNA-Protein Interactions Using Only Sequence Information,http://dx.doi.org/10.1186/1471-2105-12-489,PMC3322362,22192482,CC BY,"BACKGROUND: RNA-protein interactions (RPIs) play important roles in a wide variety of cellular processes, ranging from transcriptional and post-transcriptional regulation of gene expression to host defense against pathogens. High throughput experiments to identify RNA-protein interactions are beginning to provide valuable information about the complexity of RNA-protein interaction networks, but are expensive and time consuming. Hence, there is a need for reliable computational methods for predicting RNA-protein interactions. RESULTS: We propose RPISeq, a family of classifiers for predicting RNA-protein interactions using only sequence information. Given the sequences of an RNA and a protein as input, RPIseq predicts whether or not the RNA-protein pair interact. The RNA sequence is encoded as a normalized vector of its ribonucleotide 4-mer composition, and the protein sequence is encoded as a normalized vector of its 3-mer composition, based on a 7-letter reduced alphabet representation. Two variants of RPISeq are presented: RPISeq-SVM, which uses a Support Vector Machine (SVM) classifier and RPISeq-RF, which uses a Random Forest classifier. On two non-redundant benchmark datasets extracted from the Protein-RNA Interface Database (PRIDB), RPISeq achieved an AUC (Area Under the Receiver Operating Characteristic (ROC) curve) of 0.96 and 0.92. On a third dataset containing only mRNA-protein interactions, the performance of RPISeq was competitive with that of a published method that requires information regarding many different features (e.g., mRNA half-life, GO annotations) of the putative RNA and protein partners. In addition, RPISeq classifiers trained using the PRIDB data correctly predicted the majority (57-99%) of non-coding RNA-protein interactions in NPInter-derived networks from E. coli, S. cerevisiae, D. melanogaster, M. musculus, and H. sapiens. CONCLUSIONS: Our experiments with RPISeq demonstrate that RNA-protein interactions can be reliably predicted using only sequence-derived information. RPISeq offers an inexpensive method for computational construction of RNA-protein interaction networks, and should provide useful insights into the function of non-coding RNAs. RPISeq is freely available as a web-based server at http://pridb.gdcb.iastate.edu/RPISeq/.",2011 Dec 22,"['Muppirala, Usha K', 'Honavar, Vasant G', 'Dobbs, Drena']",BMC Bioinformatics,,,True
a50f2af4833bd314b5664e5f30a6d39792a73f5c,PMC,Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone,http://dx.doi.org/10.1371/journal.pcbi.1002454,PMC3325179,22511854,CC BY,"An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.",2012 Apr 12,"['Cooper, Ben S.', 'Kypraios, Theodore', 'Batra, Rahul', 'Wyncoll, Duncan', 'Tosas, Olga', 'Edgeworth, Jonathan D.']",PLoS Comput Biol,,,True
2c5d92ede870cbdc9d8e4b5544544c731125bc5d,PMC,Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone,http://dx.doi.org/10.1371/journal.pcbi.1002454,PMC3325179,22511854,CC BY,"An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.",2012 Apr 12,"['Cooper, Ben S.', 'Kypraios, Theodore', 'Batra, Rahul', 'Wyncoll, Duncan', 'Tosas, Olga', 'Edgeworth, Jonathan D.']",PLoS Comput Biol,,,False
de15170cb79d459586be28d687e7d68117990644,PMC,Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone,http://dx.doi.org/10.1371/journal.pcbi.1002454,PMC3325179,22511854,CC BY,"An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.",2012 Apr 12,"['Cooper, Ben S.', 'Kypraios, Theodore', 'Batra, Rahul', 'Wyncoll, Duncan', 'Tosas, Olga', 'Edgeworth, Jonathan D.']",PLoS Comput Biol,,,True
7f33a63936788ad95efb0f3d3fa1c972467b834c,PMC,Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone,http://dx.doi.org/10.1371/journal.pcbi.1002454,PMC3325179,22511854,CC BY,"An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.",2012 Apr 12,"['Cooper, Ben S.', 'Kypraios, Theodore', 'Batra, Rahul', 'Wyncoll, Duncan', 'Tosas, Olga', 'Edgeworth, Jonathan D.']",PLoS Comput Biol,,,False
a3de313c4235416a3a155a4bf154221a068ba051,PMC,Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone,http://dx.doi.org/10.1371/journal.pcbi.1002454,PMC3325179,22511854,CC BY,"An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.",2012 Apr 12,"['Cooper, Ben S.', 'Kypraios, Theodore', 'Batra, Rahul', 'Wyncoll, Duncan', 'Tosas, Olga', 'Edgeworth, Jonathan D.']",PLoS Comput Biol,,,False
ade49137a1c6f7c78b0330d906c56d7dafe52ffe,PMC,Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone,http://dx.doi.org/10.1371/journal.pcbi.1002454,PMC3325179,22511854,CC BY,"An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.",2012 Apr 12,"['Cooper, Ben S.', 'Kypraios, Theodore', 'Batra, Rahul', 'Wyncoll, Duncan', 'Tosas, Olga', 'Edgeworth, Jonathan D.']",PLoS Comput Biol,,,False
0bca7d5c8cbaf92b1d7e86518f0b42680522238a,PMC,Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone,http://dx.doi.org/10.1371/journal.pcbi.1002454,PMC3325179,22511854,CC BY,"An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.",2012 Apr 12,"['Cooper, Ben S.', 'Kypraios, Theodore', 'Batra, Rahul', 'Wyncoll, Duncan', 'Tosas, Olga', 'Edgeworth, Jonathan D.']",PLoS Comput Biol,,,False
7d2c7c6c8de76b497f0b8a4aa354f6a00b0c4854,PMC,Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone,http://dx.doi.org/10.1371/journal.pcbi.1002454,PMC3325179,22511854,CC BY,"An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.",2012 Apr 12,"['Cooper, Ben S.', 'Kypraios, Theodore', 'Batra, Rahul', 'Wyncoll, Duncan', 'Tosas, Olga', 'Edgeworth, Jonathan D.']",PLoS Comput Biol,,,False
6c9c09c364d2fbd8d8f319029e60693060b6c756,PMC,A Caprine Herpesvirus 1 Vaccine Adjuvanted with MF59™ Protects against Vaginal Infection and Interferes with the Establishment of Latency in Goats,http://dx.doi.org/10.1371/journal.pone.0034913,PMC3325274,22511971,CC BY,"The immunogenicity and the efficacy of a beta-propiolactone-inactivated caprine herpesvirus 1 (CpHV-1) vaccine adjuvanted with MF59™ were tested in goats. Following two subcutaneous immunizations, goats developed high titers of CpHV-1-specific serum and vaginal IgG and high serum virus neutralization (VN) titers. Peripheral blood mononuclear cells (PBMC) stimulated in vitro with inactivated CpHV-1 produced high levels of soluble IFN-gamma and exhibited high frequencies of IFN-gamma producing cells while soluble IL-4 was undetectable. On the other hand, control goats receiving the inactivated CpHV-1 vaccine without adjuvant produced only low serum antibody responses. A vaginal challenge with virulent CpHV-1 was performed in all vaccinated goats and in naïve goats to assess the efficacy of the two vaccines. Vaginal disease was not detected in goats vaccinated with inactivated CpHV-1 plus MF59™ and these animals had undetectable levels of infectious challenge virus in their vaginal washes. Goats vaccinated with inactivated CpHV-1 in the absence of adjuvant exhibited a less severe disease when compared to naïve goats but shed titers of challenge virus that were similar to those of naïve goats. Detection and quantitation of latent CpHV-1 DNA in sacral ganglia in challenged goats revealed that the inactivated CpHV-1 plus MF59™ vaccine was able to significantly reduce the latent viral load when compared either to the naïve goats or to the goats vaccinated with inactivated CpHV-1 in the absence of adjuvant. Thus, a vaccine composed of inactivated CpHV-1 plus MF59™ as adjuvant was strongly immunogenic and induced effective immunity against vaginal CpHV-1 infection in goats.",2012 Apr 12,"['Marinaro, Mariarosaria', 'Rezza, Giovanni', 'Del Giudice, Giuseppe', 'Colao, Valeriana', 'Tarsitano, Elvira', 'Camero, Michele', 'Losurdo, Michele', 'Buonavoglia, Canio', 'Tempesta, Maria']",PLoS One,,,True
dbf7ea2d45fff41a73853c26e5fca9862fd0edcc,PMC,Discovery and Genomic Characterization of a Novel Bat Sapovirus with Unusual Genomic Features and Phylogenetic Position,http://dx.doi.org/10.1371/journal.pone.0034987,PMC3325917,22514697,CC BY,"Sapovirus is a genus of caliciviruses that are known to cause enteric disease in humans and animals. There is considerable genetic diversity among the sapoviruses, which are classified into different genogroups based on phylogenetic analysis of the full-length capsid protein sequence. While several mammalian species, including humans, pigs, minks, and dogs, have been identified as animal hosts for sapoviruses, there were no reports of sapoviruses in bats in spite of their biological diversity. In this report, we present the results of a targeted surveillance study in different bat species in Hong Kong. Five of the 321 specimens from the bat species, Hipposideros pomona, were found to be positive for sapoviruses by RT-PCR. Complete or nearly full-length genome sequences of approximately 7.7 kb in length were obtained for three strains, which showed similar organization of the genome compared to other sapoviruses. Interestingly, they possess many genomic features atypical of most sapoviruses, like high G+C content and minimal CpG suppression. Phylogenetic analysis of the viral proteins suggested that the bat sapovirus descended from an ancestral sapovirus lineage and is most closely related to the porcine sapoviruses. Codon usage analysis showed that the bat sapovirus genome has greater codon usage bias relative to other sapovirus genomes. In summary, we report the discovery and genomic characterization of the first bat calicivirus, which appears to have evolved under different conditions after early divergence from other sapovirus lineages.",2012 Apr 13,"['Tse, Herman', 'Chan, Wan-Mui', 'Li, Kenneth S. M.', 'Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Yuen, Kwok-Yung']",PLoS One,,,True
945a7da3231e06eeb8a4a39471338e279c2e6f28,PMC,Simultaneous Identification of DNA and RNA Viruses Present in Pig Faeces Using Process-Controlled Deep Sequencing,http://dx.doi.org/10.1371/journal.pone.0034631,PMC3326065,22514648,CC BY,"BACKGROUND: Animal faeces comprise a community of many different microorganisms including bacteria and viruses. Only scarce information is available about the diversity of viruses present in the faeces of pigs. Here we describe a protocol, which was optimized for the purification of the total fraction of viral particles from pig faeces. The genomes of the purified DNA and RNA viruses were simultaneously amplified by PCR and subjected to deep sequencing followed by bioinformatic analyses. The efficiency of the method was monitored using a process control consisting of three bacteriophages (T4, M13 and MS2) with different morphology and genome types. Defined amounts of the bacteriophages were added to the sample and their abundance was assessed by quantitative PCR during the preparation procedure. RESULTS: The procedure was applied to a pooled faecal sample of five pigs. From this sample, 69,613 sequence reads were generated. All of the added bacteriophages were identified by sequence analysis of the reads. In total, 7.7% of the reads showed significant sequence identities with published viral sequences. They mainly originated from bacteriophages (73.9%) and mammalian viruses (23.9%); 0.8% of the sequences showed identities to plant viruses. The most abundant detected porcine viruses were kobuvirus, rotavirus C, astrovirus, enterovirus B, sapovirus and picobirnavirus. In addition, sequences with identities to the chimpanzee stool-associated circular ssDNA virus were identified. Whole genome analysis indicates that this virus, tentatively designated as pig stool-associated circular ssDNA virus (PigSCV), represents a novel pig virus. CONCLUSION: The established protocol enables the simultaneous detection of DNA and RNA viruses in pig faeces including the identification of so far unknown viruses. It may be applied in studies investigating aetiology, epidemiology and ecology of diseases. The implemented process control serves as quality control, ensures comparability of the method and may be used for further method optimization.",2012 Apr 13,"['Sachsenröder, Jana', 'Twardziok, Sven', 'Hammerl, Jens A.', 'Janczyk, Pawel', 'Wrede, Paul', 'Hertwig, Stefan', 'Johne, Reimar']",PLoS One,,,True
18a116d870bd24c96d95317418946ce0873f2180,PMC,Ocular pathogenesis and immune reaction after intravitreal dispase injection in mice,,PMC3327440,22511850,CC BY,"PURPOSE: The purpose of the current study was to examine the ocular pathogenesis and immune reaction in mice after intravitreal dispase injection. METHODS: Three microliters of dispase at a concentration of 0.2 U/μl were injected into the vitreal cavities of 4–6-week-old mice. Hematoxylin and eosin staining, immunofluorescence analysis, and electroretinograms of the eyes were then performed to assess ocular changes, and enzyme-linked immunospot assays and intracellular staining of single-cell suspensions of the spleens were used to detect immune changes during an 8 week observation period. RESULTS: Neutrophils were the main inflammatory infiltrating cells appearing at the anterior chamber. No cluster of differentiation (CD)3+ labeled T cells, F4/80+ labeled macrophages, or CD56+ labeled natural killer cells were found in the vitreal cavities or retinas in dispase-injected mice within 5 days after injection. Proliferative vitreoretinopathy (PVR)-like signs first appeared at 2 weeks, gradually increased thereafter, and reached peak values at 8 weeks. There was a statistically significant difference in b-wave amplitudes between the PVR and saline-control eyes. Enzyme-linked immunospot assays and intracellular staining showed that specific CD4+ and CD8+ labeled T cells were not involved in dispase-injected mice. CONCLUSIONS: Our data show that neutrophils in the anterior chamber and PVR-like signs in the retinas were found, and that specific immune reactions were not involved after intravitreal dispase injection in mice.",2012 Apr 7,"['Tan, Juan', 'Liu, Yaqin', 'Li, Wei', 'Gao, Qianying']",Mol Vis,,,True
267084b4bdfd4a3d8fbdb8d7e4c935715f3e7171,PMC,Angiotensin Converting Enzyme (ACE) and ACE2 Bind Integrins and ACE2 Regulates Integrin Signalling,http://dx.doi.org/10.1371/journal.pone.0034747,PMC3327712,22523556,CC BY,"The angiotensin converting enzymes (ACEs) are the key catalytic components of the renin-angiotensin system, mediating precise regulation of blood pressure by counterbalancing the effects of each other. Inhibition of ACE has been shown to improve pathology in cardiovascular disease, whilst ACE2 is cardioprotective in the failing heart. However, the mechanisms by which ACE2 mediates its cardioprotective functions have yet to be fully elucidated. Here we demonstrate that both ACE and ACE2 bind integrin subunits, in an RGD-independent manner, and that they can act as cell adhesion substrates. We show that cellular expression of ACE2 enhanced cell adhesion. Furthermore, we present evidence that soluble ACE2 (sACE2) is capable of suppressing integrin signalling mediated by FAK. In addition, sACE2 increases the expression of Akt, thereby lowering the proportion of the signalling molecule phosphorylated Akt. These results suggest that ACE2 plays a role in cell-cell interactions, possibly acting to fine-tune integrin signalling. Hence the expression and cleavage of ACE2 at the plasma membrane may influence cell-extracellular matrix interactions and the signalling that mediates cell survival and proliferation. As such, ectodomain shedding of ACE2 may play a role in the process of pathological cardiac remodelling.",2012 Apr 16,"['Clarke, Nicola E.', 'Fisher, Martin J.', 'Porter, Karen E.', 'Lambert, Daniel W.', 'Turner, Anthony J.']",PLoS One,,,True
83d77dc0616b9b240d13a844c7135dc250773fe0,PMC,Altered Thymic Function during Interferon Therapy in HCV-Infected Patients,http://dx.doi.org/10.1371/journal.pone.0034326,PMC3328332,22529911,CC BY,"Interferon alpha (IFNα) therapy, despite good efficacy in curing HCV infection, leads to major side effects, in particular inducement of a strong peripheral T-cell lymphocytopenia. We here analyze the early consequences of IFNα therapy on both thymic function and peripheral T-cell homeostasis in patients in the acute or chronic phase of HCV-infection as well as in HIV/HCV co-infected patients. The evolution of T-cell subsets and T-cell homeostasis were estimated by flow cytometry while thymic function was measured through quantification of T-cell receptor excision circles (TREC) and estimation of intrathymic precursor T-cell proliferation during the first four months following the initiation of IFNα therapy. Beginning with the first month of therapy, a profound lymphocytopenia was observed for all T-cell subsets, including naïve T-cells and recent thymic emigrants (RTE), associated with inhibition of intrathymic precursor T-cell proliferation. Interleukin (IL)-7 plasma concentration rapidly dropped while lymphocytopenia progressed. This was neither a consequence of higher consumption of the cytokine nor due to its neutralization by soluble CD127. Decrease in IL-7 plasma concentration under IFNα therapy correlated with the decline in HCV viral load, thymic activity and RTE concentration in blood. These data demonstrate that IFNα-based therapy rapidly impacts on thymopoiesis and, consequently, perturbs T-cell homeostasis. Such a side effect might be detrimental for the continuation of IFNα therapy and may lead to an increased level of infectious risk, in particular in HIV/HCV co-infected patients. Altogether, this study suggests the therapeutic potential of IL-7 in the maintenance of peripheral T-cell homeostasis in IFNα-treated patients.",2012 Apr 16,"['Beq, Stephanie', 'Rozlan, Sandra', 'Pelletier, Sandy', 'Willems, Bernard', 'Bruneau, Julie', 'Lelievre, Jean-Daniel', 'Levy, Yves', 'Shoukry, Naglaa H.', 'Cheynier, Rémi']",PLoS One,,,True
f5edded3536428635cad1f78fe6dc38002690a43,PMC,Current Situation and Perspectives of Clinical Study in Integrative Medicine in China,http://dx.doi.org/10.1155/2012/268542,PMC3328953,22550539,CC BY,"Integrative medicine is not only an innovative China model in clinical practice, but also the bridge for TCM toward the world. In the past thirty years, great achievements have been made in integrative medicine researches, especially in clinical practice. The clinical achievements mainly include the following three: innovating methodology of disease-syndrome combination, excavating the classical theory in traditional Chinese medicine (TCM), preventing and curing refractory diseases. The development ideas and strategies of integrative medicine for future mainly include (a) standing on frontier field of international medicine and improving the capability of preventing and curing refractory diseases; (b) moving prevention and control strategy forward and improving the curative effect of common and frequent disease; (c) excavating the classical theory of TCM and broadening the treatment system of modern medicine; (d) improving the innovation level of new high effective drugs on the basis of classical prescriptions and herbs in TCM; (e) rerecognizing the theory of formula corresponding to syndrome in TCM and enhancing the level of clinical research evidence based on evidence-based medicine. Integrative medicine will do obtain greater achievements in creating new medicine and pharmacology and make more tremendous contributions for the great rejuvenation of the Chinese nation and human health care.",2012 Feb 21,"['Wang, Jie', 'Xiong, Xingjiang']",Evid Based Complement Alternat Med,,,True
c9653d4f2d22837f98e2be157df9dd6516c1ec96,PMC,Pathogenesis and Tissue Distribution of Avian Infectious Bronchitis Virus Isolate IRFIBV32 (793/B Serotype) in Experimentally Infected Broiler Chickens,http://dx.doi.org/10.1100/2012/402537,PMC3329954,22566769,CC BY,"Infectious bronchitis (IB) is one of the most important viral diseases of poultry. The aim of this study was to investigate the distribution of avian infectious bronchitis virus isolate IRFIBV32 (793/B serotype) in experimentally infected chicken. Ninety-one-day-old commercial broilers were divided randomly into two groups (seventy in the experimental and twenty in the control group). Chicks in the experimental group were inoculated intranasally with 10(5) ELD50/0.1 mL of the virus at three weeks of age. The samples from various tissues were collected at1, 2, 3, 5, 7, 11, 13, 15, and 20 days postinoculation. Chickens exhibited mild respiratory signs and depression. Viral RNA was detected in the kidney, lung and tracheas on days 1 to 13 PI, in the oviduct between, days 3 and 13, in testes between days 1 and 11 PI, and in the caecal tonsil consistently up to day 20 PI. The most remarkable clinical signs and virus detection appeared on day 1 PI. Data indicated that the number of infected chickens and viral RNA detection from tissues was reduced with increasing antibody titer on day 20 PI. The results demonstrated that the IRFIBV32 virus has wide tissue distribution for respiratory, urogenital, and digestive systems.",2012 Apr 1,"['Boroomand, Zahra', 'Asasi, Keramat', 'Mohammadi, Ali']",ScientificWorldJournal,,,True
b82539a18c6aea935321822f2de5937fd7fef769,PMC,Pandemic 2009 H1N1 virus infection in children and adults: A cohort study at a single hospital throughout the epidemic,http://dx.doi.org/10.1186/1755-7682-5-13,PMC3331808,22443897,CC BY,"BACKGROUND: In 2009, there was an influenza pandemic in South Korea. The aim of this study was to evaluate the epidemiological, clinical and laboratory characteristics of this infection in children and adults. METHODS: We evaluated the epidemiologic characteristics of patients infected with the 2009 H1N1 influenza A virus (4,463 patients, age range from 2 mo to 86 y), and the clinical and laboratory findings of 373 inpatients (80/217 children, ≤ 15 y, had pneumonia and 36/156 adults, > 16 y, had pneumonia) in a single hospital during the epidemic. RESULTS: The majority of infected patients (94%) were less than 40 y, and greater than 90% of cases occurred during a two-month period. The rates of admission and pneumonia were 8.4% (373/4,463) and 2.5% (116/4,463), respectively. The rates of admission and pneumonia, total duration of fever, the frequency of underlying diseases, and the values of C-reactive protein and erythrocyte sedimentation rate tended to increase as age increased; highest rates were found in the ≥ 65 y group. Pneumonia was founded more boys than girls in children, but more female than male in adults. The adult patients with pneumonia had higher leukocyte counts with lower lymphocyte differentials than the group without pneumonia, as shown in children group. CONCLUSION: Our results suggest that the immunologic reaction to viral insults may be associated with age, sex and underlying diseases, and that unknown herd immunity may affect populations. The patients with underlying diseases, especially in older patients may have immunologic insufficiency that is associated with immunologic consumption by the underlying diseases.",2012 Mar 26,"['Rhim, Jung-Woo', 'Go, Eun-Ji', 'Lee, Kyung-Yil', 'Youn, You-Sook', 'Kim, Myung-Sook', 'Park, Sun Hee', 'Kim, Ji-Chang', 'Kang, Jin-Han']",Int Arch Med,,,True
11ad2acc16067afbf2ce40d422647c3d899ecbd4,PMC,Cough aerosol in healthy participants: fundamental knowledge to optimize droplet-spread infectious respiratory disease management,http://dx.doi.org/10.1186/1471-2466-12-11,PMC3331822,22436202,CC BY,"BACKGROUND: The Influenza A H1N1 virus can be transmitted via direct, indirect, and airborne route to non-infected subjects when an infected patient coughs, which expels a number of different sized droplets to the surrounding environment as an aerosol. The objective of the current study was to characterize the human cough aerosol pattern with the aim of developing a standard human cough bioaerosol model for Influenza Pandemic control. METHOD: 45 healthy non-smokers participated in the open bench study by giving their best effort cough. A laser diffraction system was used to obtain accurate, time-dependent, quantitative measurements of the size and number of droplets expelled by the cough aerosol. RESULTS: Voluntary coughs generated droplets ranging from 0.1 - 900 microns in size. Droplets of less than one-micron size represent 97% of the total number of measured droplets contained in the cough aerosol. Age, sex, weight, height and corporal mass have no statistically significant effect on the aerosol composition in terms of size and number of droplets. CONCLUSIONS: We have developed a standard human cough aerosol model. We have quantitatively characterized the pattern, size, and number of droplets present in the most important mode of person-to-person transmission of IRD: the cough bioaerosol. Small size droplets (< 1 μm) predominated the total number of droplets expelled when coughing. The cough aerosol is the single source of direct, indirect and/or airborne transmission of respiratory infections like the Influenza A H1N1 virus. STUDY DESIGN: Open bench, Observational, Cough, Aerosol study",2012 Mar 21,"['Zayas, Gustavo', 'Chiang, Ming C', 'Wong, Eric', 'MacDonald, Fred', 'Lange, Carlos F', 'Senthilselvan, Ambikaipakan', 'King, Malcolm']",BMC Pulm Med,,,True
4e388424e65f63b5cc6b567b0980d430cb2d738c,PMC,Transmission Electron Microscopy Studies of Cellular Responses to Entry of Virions: One Kind of Natural Nanobiomaterial,http://dx.doi.org/10.1155/2012/596589,PMC3332201,22567012,CC BY,"Virions are one kind of nanoscale pathogen and are able to infect living cells of animals, plants, and bacteria. The infection is an intrinsic property of the virions, and the biological process provides a good model for studying how these nanoparticles enter into cells. During the infection, the viruses employ different strategies to which the cells have developed respective responses. For this paper, we chose Bombyx mori cypovirus 1 (BmCPV-1) interactions with midgut cells from silkworm, and severe acute respiratory syndrome (SARS) associated coronavirus interactions with Vero E6 cells, as examples to demonstrate the response of eukaryotic cells to two different types of virus from our previous studies. The bacteriophage-bacteria interactions are also introduced to elucidate how the bacteriophage conquers the barrier of cell walls in the prokaryotic cells to transport genome into the host.",2012 Apr 11,"['Liu, Zheng', 'Liu, Shuyu', 'Cui, Jinming', 'Tan, Yurong', 'He, Jian', 'Zhang, Jingqiang']",Int J Cell Biol,,,True
695f0e7afa181c640a015a3b43d1ae401435107a,PMC,"Coordination and resource-related difficulties encountered by Quebec's public health specialists and infectious diseases/medical microbiologists in the management of A (H1N1) - a mixed-method, exploratory survey",http://dx.doi.org/10.1186/1471-2458-12-115,PMC3332281,22325707,CC BY,"BACKGROUND: In Quebec, the influenza A (H1N1) pandemic was managed using a top-down style that left many involved players with critical views and frustrations. We aimed to describe physicians' perceptions - infectious diseases specialists/medical microbiologists (IDMM) and public health/preventive medicine specialists (PHPMS) - in regards to issues encountered with the pandemics management at the physician level and highlight suggested improvements for future healthcare emergencies. METHODS: In April 2010, Quebec IDMM and PHPMS physicians were invited to anonymously complete a web-based learning needs assessment. The survey included both open-ended and multiple-choice questions. Descriptive statistics were used to report on the frequency distribution of multiple choice responses whereas thematic content analysis was used to analyse qualitative data generated from the survey and help understand respondents' experience and perceptions with the pandemics. RESULTS: Of the 102 respondents, 85.3% reported difficulties or frustrations in their practice during the pandemic. The thematic analysis revealed two core themes describing the problems experienced in the pandemic management: coordination and resource-related difficulties. Coordination issues included communication, clinical practice guidelines, decision-making, roles and responsibilities, epidemiological investigation, and public health expert advisory committees. Resources issues included laboratory resources, patient management, and vaccination process. CONCLUSION: Together, the quantitative and qualitative data suggest a need for improved coordination, a better definition of roles and responsibilities, increased use of information technologies, merged communications, and transparency in the decisional process. Increased flexibility and less contradiction in clinical practice guidelines from different sources and increased laboratory/clinical capacity were felt critical to the proper management of infectious disease emergencies.",2012 Feb 10,"['Nhan, Charles', 'Laprise, Réjean', 'Douville-Fradet, Monique', 'Macdonald, Mary Ellen', 'Quach, Caroline']",BMC Public Health,,,True
d17d9c2e082583da2dba7cfc61995f5af37e6851,PMC,Protective Immunity to Listeria Monocytogenes Infection Mediated by Recombinant Listeria innocua Harboring the VGC Locus,http://dx.doi.org/10.1371/journal.pone.0035503,PMC3334901,22536395,CC BY,"In this study we propose a novel bacterial vaccine strategy where non-pathogenic bacteria are complemented with traits desirable for the induction of protective immunity. To illustrate the proof of principle of this novel vaccination strategy, we use the model organism of intracellular immunity Listeria. We introduced a, low copy number BAC-plasmid harbouring the virulence gene cluster (vgc) of L. monocytogenes (Lm) into the non-pathogenic L. innocua (L.inn) strain and examined for its ability to induce protective cellular immunity. The resulting strain (L.inn::vgc) was attenuated for virulence in vivo and showed a strongly reduced host detrimental inflammatory response compared to Lm. Like Lm, L.inn::vgc induced the production of Type I Interferon's and protection was mediated by Listeria-specific CD8(+) T cells. Rational vaccine design whereby avirulent strains are equipped with the capabilities to induce protection but lack detrimental inflammatory effects offer great promise towards future studies using non-pathogenic bacteria as vectors for vaccination.",2012 Apr 19,"['Mohamed, Walid', 'Sethi, Shneh', 'Tchatalbachev, Svetlin', 'Darji, Ayub', 'Chakraborty, Trinad']",PLoS One,,,True
ca7514c743f1cab0c939328f75ff231ba9d9079d,PMC,Anti-HIV-1 Activity of a New Scorpion Venom Peptide Derivative Kn2-7,http://dx.doi.org/10.1371/journal.pone.0034947,PMC3334916,22536342,CC BY,"For over 30 years, HIV/AIDS has wreaked havoc in the world. In the absence of an effective vaccine for HIV, development of new anti-HIV agents is urgently needed. We previously identified the antiviral activities of the scorpion-venom-peptide-derived mucroporin-M1 for three RNA viruses (measles viruses, SARS-CoV, and H5N1). In this investigation, a panel of scorpion venom peptides and their derivatives were designed and chosen for assessment of their anti-HIV activities. A new scorpion venom peptide derivative Kn2-7 was identified as the most potent anti-HIV-1 peptide by screening assays with an EC(50) value of 2.76 µg/ml (1.65 µM) and showed low cytotoxicity to host cells with a selective index (SI) of 13.93. Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV) with CCR5-tropic and CXCR4-tropic NL4-3 PV strain. Furthermore, it also inhibited a CXCR4-tropic replication-competent strain of HIV-1 subtype B virus. Binding assay of Kn2-7 to HIV-1 PV by Octet Red system suggested the anti-HIV-1 activity was correlated with a direct interaction between Kn2-7 and HIV-1 envelope. These results demonstrated that peptide Kn2-7 could inhibit HIV-1 by direct interaction with viral particle and may become a promising candidate compound for further development of microbicide against HIV-1.",2012 Apr 19,"['Chen, Yaoqing', 'Cao, Luyang', 'Zhong, Maohua', 'Zhang, Yan', 'Han, Chen', 'Li, Qiaoli', 'Yang, Jingyi', 'Zhou, Dihan', 'Shi, Wei', 'He, Benxia', 'Liu, Fang', 'Yu, Jie', 'Sun, Ying', 'Cao, Yuan', 'Li, Yaoming', 'Li, Wenxin', 'Guo, Deying', 'Cao, Zhijian', 'Yan, Huimin']",PLoS One,,,True
21268687c8044a9acd561589e1f291f0843c6678,PMC,Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing,http://dx.doi.org/10.1371/journal.pone.0035009,PMC3334963,22536348,CC BY,"BACKGROUND: The Manila clam (Ruditapes philippinarum) is a worldwide cultured bivalve species with important commercial value. Diseases affecting this species can result in large economic losses. Because knowledge of the molecular mechanisms of the immune response in bivalves, especially clams, is scarce and fragmentary, we sequenced RNA from immune-stimulated R. philippinarum hemocytes by 454-pyrosequencing to identify genes involved in their immune defense against infectious diseases. METHODOLOGY AND PRINCIPAL FINDINGS: High-throughput deep sequencing of R. philippinarum using 454 pyrosequencing technology yielded 974,976 high-quality reads with an average read length of 250 bp. The reads were assembled into 51,265 contigs and the 44.7% of the translated nucleotide sequences into protein were annotated successfully. The 35 most frequently found contigs included a large number of immune-related genes, and a more detailed analysis showed the presence of putative members of several immune pathways and processes like the apoptosis, the toll like signaling pathway and the complement cascade. We have found sequences from molecules never described in bivalves before, especially in the complement pathway where almost all the components are present. CONCLUSIONS: This study represents the first transcriptome analysis using 454-pyrosequencing conducted on R. philippinarum focused on its immune system. Our results will provide a rich source of data to discover and identify new genes, which will serve as a basis for microarray construction and the study of gene expression as well as for the identification of genetic markers. The discovery of new immune sequences was very productive and resulted in a large variety of contigs that may play a role in the defense mechanisms of Ruditapes philippinarum.",2012 Apr 19,"['Moreira, Rebeca', 'Balseiro, Pablo', 'Planas, Josep V.', 'Fuste, Berta', 'Beltran, Sergi', 'Novoa, Beatriz', 'Figueras, Antonio']",PLoS One,,,True
69ed0332751ba504d01cf6d6c266c9ae499ceb38,PMC,Airflow Dynamics of Coughing in Healthy Human Volunteers by Shadowgraph Imaging: An Aid to Aerosol Infection Control,http://dx.doi.org/10.1371/journal.pone.0034818,PMC3335026,22536332,CC BY,"Cough airflow dynamics have been previously studied using a variety of experimental methods. In this study, real-time, non-invasive shadowgraph imaging was applied to obtain additional analyses of cough airflows produced by healthy volunteers. Twenty healthy volunteers (10 women, mean age 32.2±12.9 years; 10 men, mean age 25.3±2.5 years) were asked to cough freely, then into their sleeves (as per current US CDC recommendations) in this study to analyze cough airflow dynamics. For the 10 females (cases 1–10), their maximum detectable cough propagation distances ranged from 0.16–0.55 m, with maximum derived velocities of 2.2–5.0 m/s, and their maximum detectable 2-D projected areas ranged from 0.010–0.11 m(2), with maximum derived expansion rates of 0.15–0.55 m(2)/s. For the 10 males (cases 11–20), their maximum detectable cough propagation distances ranged from 0.31–0.64 m, with maximum derived velocities of 3.2–14 m/s, and their maximum detectable 2-D projected areas ranged from 0.04–0.14 m(2), with maximum derived expansion rates of 0.25–1.4 m(2)/s. These peak velocities were measured when the visibility of the exhaled airflows was optimal and compare favorably with those reported previously using other methods, and may be seen as a validation of these previous approaches in a more natural setting. However, the propagation distances can only represent a lower limit due to the inability of the shadowgraph method to visualize these cough airflows once their temperature cools to that of the ambient air, which is an important limitation of this methodology. The qualitative high-speed video footage of these volunteers coughing into their sleeves demonstrates that although this method rarely completely blocks the cough airflow, it decelerates, splits and redirects the airflow, eventually reducing its propagation. The effectiveness of this intervention depends on optimum positioning of the arm over the nose and mouth during coughing, though unsightly stains on sleeves may make it unacceptable to some.",2012 Apr 20,"['Tang, Julian W.', 'Nicolle, Andre', 'Pantelic, Jovan', 'Koh, Gerald C.', 'Wang, Liang De', 'Amin, Muhammad', 'Klettner, Christian A.', 'Cheong, David K. W.', 'Sekhar, Chandra', 'Tham, Kwok Wai']",PLoS One,,,True
962c58e6dc9c1ea550eb51ce70b0d7c83dc7eff6,PMC,Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus,http://dx.doi.org/10.1371/journal.pone.0035421,PMC3335060,22536382,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS) emerged in China in 2002 and spread to other countries before brought under control. Because of a concern for reemergence or a deliberate release of the SARS coronavirus, vaccine development was initiated. Evaluations of an inactivated whole virus vaccine in ferrets and nonhuman primates and a virus-like-particle vaccine in mice induced protection against infection but challenged animals exhibited an immunopathologic-type lung disease. DESIGN: Four candidate vaccines for humans with or without alum adjuvant were evaluated in a mouse model of SARS, a VLP vaccine, the vaccine given to ferrets and NHP, another whole virus vaccine and an rDNA-produced S protein. Balb/c or C57BL/6 mice were vaccinated IM on day 0 and 28 and sacrificed for serum antibody measurements or challenged with live virus on day 56. On day 58, challenged mice were sacrificed and lungs obtained for virus and histopathology. RESULTS: All vaccines induced serum neutralizing antibody with increasing dosages and/or alum significantly increasing responses. Significant reductions of SARS-CoV two days after challenge was seen for all vaccines and prior live SARS-CoV. All mice exhibited histopathologic changes in lungs two days after challenge including all animals vaccinated (Balb/C and C57BL/6) or given live virus, influenza vaccine, or PBS suggesting infection occurred in all. Histopathology seen in animals given one of the SARS-CoV vaccines was uniformly a Th2-type immunopathology with prominent eosinophil infiltration, confirmed with special eosinophil stains. The pathologic changes seen in all control groups lacked the eosinophil prominence. CONCLUSIONS: These SARS-CoV vaccines all induced antibody and protection against infection with SARS-CoV. However, challenge of mice given any of the vaccines led to occurrence of Th2-type immunopathology suggesting hypersensitivity to SARS-CoV components was induced. Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated.",2012 Apr 20,"['Tseng, Chien-Te', 'Sbrana, Elena', 'Iwata-Yoshikawa, Naoko', 'Newman, Patrick C.', 'Garron, Tania', 'Atmar, Robert L.', 'Peters, Clarence J.', 'Couch, Robert B.']",PLoS One,,,True
9b034efc9d262e8687f1ad7adb78fa7374d3e5ad,PMC,The Influence of Meteorology on the Spread of Influenza: Survival Analysis of an Equine Influenza (A/H3N8) Outbreak,http://dx.doi.org/10.1371/journal.pone.0035284,PMC3335077,22536366,CC BY,"The influences of relative humidity and ambient temperature on the transmission of influenza A viruses have recently been established under controlled laboratory conditions. The interplay of meteorological factors during an actual influenza epidemic is less clear, and research into the contribution of wind to epidemic spread is scarce. By applying geostatistics and survival analysis to data from a large outbreak of equine influenza (A/H3N8), we quantified the association between hazard of infection and air temperature, relative humidity, rainfall, and wind velocity, whilst controlling for premises-level covariates. The pattern of disease spread in space and time was described using extraction mapping and instantaneous hazard curves. Meteorological conditions at each premises location were estimated by kriging daily meteorological data and analysed as time-lagged time-varying predictors using generalised Cox regression. Meteorological covariates time-lagged by three days were strongly associated with hazard of influenza infection, corresponding closely with the incubation period of equine influenza. Hazard of equine influenza infection was higher when relative humidity was <60% and lowest on days when daily maximum air temperature was 20–25°C. Wind speeds >30 km hour(−1) from the direction of nearby infected premises were associated with increased hazard of infection. Through combining detailed influenza outbreak and meteorological data, we provide empirical evidence for the underlying environmental mechanisms that influenced the local spread of an outbreak of influenza A. Our analysis supports, and extends, the findings of studies into influenza A transmission conducted under laboratory conditions. The relationships described are of direct importance for managing disease risk during influenza outbreaks in horses, and more generally, advance our understanding of the transmission of influenza A viruses under field conditions.",2012 Apr 20,"['Firestone, Simon M.', 'Cogger, Naomi', 'Ward, Michael P.', 'Toribio, Jenny-Ann L. M. L.', 'Moloney, Barbara J.', 'Dhand, Navneet K.']",PLoS One,,,True
0cf8f9fb2f0481a0e6a4b83cbffb07acfa20d6b0,PMC,Synthetic Biology: Mapping the Scientific Landscape,http://dx.doi.org/10.1371/journal.pone.0034368,PMC3335118,22539946,CC BY,"This article uses data from Thomson Reuters Web of Science to map and analyse the scientific landscape for synthetic biology. The article draws on recent advances in data visualisation and analytics with the aim of informing upcoming international policy debates on the governance of synthetic biology by the Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA) of the United Nations Convention on Biological Diversity. We use mapping techniques to identify how synthetic biology can best be understood and the range of institutions, researchers and funding agencies involved. Debates under the Convention are likely to focus on a possible moratorium on the field release of synthetic organisms, cells or genomes. Based on the empirical evidence we propose that guidance could be provided to funding agencies to respect the letter and spirit of the Convention on Biological Diversity in making research investments. Building on the recommendations of the United States Presidential Commission for the Study of Bioethical Issues we demonstrate that it is possible to promote independent and transparent monitoring of developments in synthetic biology using modern information tools. In particular, public and policy understanding and engagement with synthetic biology can be enhanced through the use of online interactive tools. As a step forward in this process we make existing data on the scientific literature on synthetic biology available in an online interactive workbook so that researchers, policy makers and civil society can explore the data and draw conclusions for themselves.",2012 Apr 23,"['Oldham, Paul', 'Hall, Stephen', 'Burton, Geoff']",PLoS One,,,True
b2b5a490834c8b80177d322022e6c5c0828a5eaa,PMC,Schizophrenia: A Pathogenetic Autoimmune Disease Caused by Viruses and Pathogens and Dependent on Genes,http://dx.doi.org/10.4061/2011/128318,PMC3335463,22567321,CC BY,"Many genes have been implicated in schizophrenia as have viral prenatal or adult infections and toxoplasmosis or Lyme disease. Several autoantigens also target key pathology-related proteins. These factors are interrelated. Susceptibility genes encode for proteins homologous to those of the pathogens while the autoantigens are homologous to pathogens' proteins, suggesting that the risk-promoting effects of genes and risk factors are conditional upon each other, and dependent upon protein matching between pathogen and susceptibility gene products. Pathogens' proteins may act as dummy ligands, decoy receptors, or via interactome interference. Many such proteins are immunogenic suggesting that antibody mediated knockdown of multiple schizophrenia gene products could contribute to the disease, explaining the immune activation in the brain and lymphocytes in schizophrenia, and the preponderance of immune-related gene variants in the schizophrenia genome. Schizophrenia may thus be a “pathogenetic” autoimmune disorder, caused by pathogens, genes, and the immune system acting together, and perhaps preventable by pathogen elimination, or curable by the removal of culpable antibodies and antigens.",2011 May 26,"Carter, C. J.",J Pathog,,,True
05bdc3cf6dad125ad6539580352cb341eeaec2b1,PMC,Activation of P2X(7) Receptor by ATP Plays an Important Role in Regulating Inflammatory Responses during Acute Viral Infection,http://dx.doi.org/10.1371/journal.pone.0035812,PMC3338466,22558229,CC BY,"Acute viral infection causes damages to the host due to uncontrolled viral replication but even replication deficient viral vectors can induce systemic inflammatory responses. Indeed, overactive host innate immune responses to viral vectors have led to devastating consequences. Macrophages are important innate immune cells that recognize viruses and induce inflammatory responses at the early stage of infection. However, tissue resident macrophages are not easily activated by the mere presence of virus suggesting that their activation requires additional signals from other cells in the tissue in order to trigger inflammatory responses. Previously, we have shown that the cross-talk between epithelial cells and macrophages generates synergistic inflammatory responses during adenoviral vector infection. Here, we investigated whether ATP is involved in the activation of macrophages to induce inflammatory responses during an acute adenoviral infection. Using a macrophage-epithelial cell co-culture system we demonstrated that ATP signaling through P2X(7) receptor (P2X(7)R) is required for induction of inflammatory mediators. We also showed that ATP-P2X(7)R signaling regulates inflammasome activation as inhibition or deficiency of P2X(7)R as well as caspase-1 significantly reduced IL-1β secretion. Furthermore, we found that intranasal administration of replication deficient adenoviral vectors in mice caused a high mortality in wild-type mice with symptoms of acute respiratory distress syndrome but the mice deficient in P2X(7)R or caspase-1 showed increased survival. In addition, wild-type mice treated with apyrase or inhibitors of P2X(7)R or caspase-1 showed higher rates of survival. The improved survival in the P2X(7)R deficient mice correlated with diminished levels of IL-1β and IL-6 and reduced neutrophil infiltration in the early phase of infection. These results indicate that ATP, released during viral infection, is an important inflammatory regulator that activates the inflammasome pathway and regulates inflammatory responses.",2012 Apr 25,"['Lee, Benjamin H.', 'Hwang, David M.', 'Palaniyar, Nades', 'Grinstein, Sergio', 'Philpott, Dana J.', 'Hu, Jim']",PLoS One,,,True
04d9df812fd77e1231263d42ab45e570cd94d956,PMC,Aerosol Generating Procedures and Risk of Transmission of Acute Respiratory Infections to Healthcare Workers: A Systematic Review,http://dx.doi.org/10.1371/journal.pone.0035797,PMC3338532,22563403,CC BY,"Aerosol generating procedures (AGPs) may expose health care workers (HCWs) to pathogens causing acute respiratory infections (ARIs), but the risk of transmission of ARIs from AGPs is not fully known. We sought to determine the clinical evidence for the risk of transmission of ARIs to HCWs caring for patients undergoing AGPs compared with the risk of transmission to HCWs caring for patients not undergoing AGPs. We searched PubMed, EMBASE, MEDLINE, CINAHL, the Cochrane Library, University of York CRD databases, EuroScan, LILACS, Indian Medlars, Index Medicus for SE Asia, international health technology agencies and the Internet in all languages for articles from 01/01/1990 to 22/10/2010. Independent reviewers screened abstracts using pre-defined criteria, obtained full-text articles, selected relevant studies, and abstracted data. Disagreements were resolved by consensus. The outcome of interest was risk of ARI transmission. The quality of evidence was rated using the GRADE system. We identified 5 case-control and 5 retrospective cohort studies which evaluated transmission of SARS to HCWs. Procedures reported to present an increased risk of transmission included [n; pooled OR(95%CI)] tracheal intubation [n = 4 cohort; 6.6 (2.3, 18.9), and n = 4 case-control; 6.6 (4.1, 10.6)], non-invasive ventilation [n = 2 cohort; OR 3.1(1.4, 6.8)], tracheotomy [n = 1 case-control; 4.2 (1.5, 11.5)] and manual ventilation before intubation [n = 1 cohort; OR 2.8 (1.3, 6.4)]. Other intubation associated procedures, endotracheal aspiration, suction of body fluids, bronchoscopy, nebulizer treatment, administration of O2, high flow O2, manipulation of O2 mask or BiPAP mask, defibrillation, chest compressions, insertion of nasogastric tube, and collection of sputum were not significant. Our findings suggest that some procedures potentially capable of generating aerosols have been associated with increased risk of SARS transmission to HCWs or were a risk factor for transmission, with the most consistent association across multiple studies identified with tracheal intubation.",2012 Apr 26,"['Tran, Khai', 'Cimon, Karen', 'Severn, Melissa', 'Pessoa-Silva, Carmem L.', 'Conly, John']",PLoS One,,,True
a23e98e1cc196167116f87f71aae771739bdf0d0,PMC,Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus,http://dx.doi.org/10.1371/journal.pone.0036238,PMC3338671,22558400,CC BY,"BACKGROUND: The white backed planthopper (WBPH), Sogatella furcifera (Horváth), causes great damage to many crops by direct feeding or transmitting plant viruses. Southern rice black-streaked dwarf virus (SRBSDV), transmitted by WBPH, has become a great threat to rice production in East Asia. METHODOLOGY/PRINCIPAL FINDINGS: By de novo transcriptome assembling and massive parallel pyrosequencing, we constructed two transcriptomes of WBPH and profiled the alternation of gene expression in response to SRBSDV infection in transcriptional level. Over 25 million reads of high-quality DNA sequences and 81388 different unigenes were generated using Illumina technology from both viruliferous and non-viruliferous WBPH. WBPH has a very similar gene ontological distribution to other two closely related rice planthoppers, Nilaparvata lugens and Laodelphax striatellus. 7291 microsatellite loci were also predicted which could be useful for further evolutionary analysis. Furthermore, comparative analysis of the two transcriptomes generated from viruliferous and non-viruliferous WBPH provided a list of candidate transcripts that potentially were elicited as a response to viral infection. Pathway analyses of a subset of these transcripts indicated that SRBSDV infection may perturb primary metabolism and the ubiquitin-proteasome pathways. In addition, 5.5% (181 out of 3315) of the genes in cell cytoskeleton organization pathway showed obvious changes. Our data also demonstrated that SRBSDV infection activated the immunity regulatory systems of WBPH, such as RNA interference, autophagy and antimicrobial peptide production. CONCLUSIONS/SIGNIFICANCE: We employed massively parallel pyrosequencing to collect ESTs from viruliferous and non-viruliferous samples of WBPH. 81388 different unigenes have been obtained. We for the first time described the direct effects of a Reoviridae family plant virus on global gene expression profiles of its insect vector using high-throughput sequencing. Our study will provide a road map for future investigations of the fascinating interactions between Reoviridae viruses and their insect vectors, and provide new strategies for crop protection.",2012 Apr 27,"['Xu, Yi', 'Zhou, Wenwu', 'Zhou, Yijun', 'Wu, Jianxiang', 'Zhou, Xueping']",PLoS One,,,True
aff7baf924af877c824d6c9c1132caa094342636,PMC,"Replication, Neurotropism, and Pathogenicity of Avian Paramyxovirus Serotypes 1–9 in Chickens and Ducks",http://dx.doi.org/10.1371/journal.pone.0034927,PMC3340391,22558104,CC0,"Avian paramyxovirus (APMV) serotypes 1–9 have been isolated from many different avian species. APMV-1 (Newcastle disease virus) is the only well-characterized serotype, because of the high morbidity, mortality, and economic loss caused by highly virulent strains. Very little is known about the pathogenesis, replication, virulence, and tropism of the other APMV serotypes. Here, this was evaluated for prototypes strains of APMV serotypes 2–9 in cell culture and in chickens and ducks. In cell culture, only APMV-1, -3 and -5 induced syncytium formation. In chicken DF1 cells, APMV-3 replicated with an efficiency approaching that of APMV-1, while APMV-2 and -5 replicated to lower, intermediate titers and the others were much lower. Mean death time (MDT) assay in chicken eggs and intracerebral pathogenicity index (ICPI) test in 1-day-old SPF chicks demonstrated that APMV types 2–9 were avirulent. Evaluation of replication in primary neuronal cells in vitro as well as in the brains of 1-day-old chicks showed that, among types 2–9, only APMV-3 was neurotropic, although this virus was not neurovirulent. Following intranasal infection of 1-day-old and 2-week-old chickens, replication of APMV types 2–9 was mostly restricted to the respiratory tract, although APMV-3 was neuroinvasive and neurotropic (but not neurovirulent) and also was found in the spleen. Experimental intranasal infection of 3-week-old mallard ducks with the APMVs did not produce any clinical signs (even for APMV-1) and exhibited restricted viral replication of the APMVs (including APMV-1) to the upper respiratory tract regardless of their isolation source, indicating avirulence of APMV types 1–9 in mallard ducks. The link between the presence of a furin cleavage site in the F protein, syncytium formation, systemic spread, and virulence that has been well-established with APMV-1 pathotypes was not evident with the other APMV serotypes.",2012 Apr 30,"['Kim, Shin-Hee', 'Xiao, Sa', 'Shive, Heather', 'Collins, Peter L.', 'Samal, Siba K.']",PLoS One,,,True
ba3522d00ecebd159c5b5dc90119df8642993c49,PMC,Influenza and SARS-Coronavirus Activating Proteases TMPRSS2 and HAT Are Expressed at Multiple Sites in Human Respiratory and Gastrointestinal Tracts,http://dx.doi.org/10.1371/journal.pone.0035876,PMC3340400,22558251,CC BY,"The type II transmembrane serine proteases TMPRSS2 and HAT activate influenza viruses and the SARS-coronavirus (TMPRSS2) in cell culture and may play an important role in viral spread and pathogenesis in the infected host. However, it is at present largely unclear to what extent these proteases are expressed in viral target cells in human tissues. Here, we show that both HAT and TMPRSS2 are coexpressed with 2,6-linked sialic acids, the major receptor determinant of human influenza viruses, throughout the human respiratory tract. Similarly, coexpression of ACE2, the SARS-coronavirus receptor, and TMPRSS2 was frequently found in the upper and lower aerodigestive tract, with the exception of the vocal folds, epiglottis and trachea. Finally, activation of influenza virus was conserved between human, avian and porcine TMPRSS2, suggesting that this protease might activate influenza virus in reservoir-, intermediate- and human hosts. In sum, our results show that TMPRSS2 and HAT are expressed by important influenza and SARS-coronavirus target cells and could thus support viral spread in the human host.",2012 Apr 30,"['Bertram, Stephanie', 'Heurich, Adeline', 'Lavender, Hayley', 'Gierer, Stefanie', 'Danisch, Simon', 'Perin, Paula', 'Lucas, Jared M.', 'Nelson, Peter S.', 'Pöhlmann, Stefan', 'Soilleux, Elizabeth J.']",PLoS One,,,True
d2263b3300cd722dfbadc7c40008126d95ab4af6,PMC,Patterns and influencing factor of synonymous codon usage in porcine circovirus,http://dx.doi.org/10.1186/1743-422X-9-68,PMC3341187,22416942,CC BY,"BACKGROUND: Analysis of codon usage can reveal much about the molecular evolution of the viruses. Nevertheless, little information about synonymous codon usage pattern of porcine circovirus (PCV) genome in the process of its evolution is available. In this study, to give a new understanding on the evolutionary characteristics of PCV and the effects of natural selection from its host on the codon usage pattern of the virus, Patterns and the key determinants of codon usage in PCV were examined. METHODS: We carried out comprehensive analysis on codon usage pattern in the PCV genome, by calculating relative synonymous codon usage (RSCU), effective number of codons (ENC), dinucleotides and nucleic acid content of the PCV genome. RESULTS: PCV genomes have relatively much lower content of GC and codon preference, this result shows that nucleotide constraints have a major impact on its synonymous codon usage. The results of the correspondence analysis indicate codon usage patterns of PCV of various genotypes, various subgenotypes changed greatly, and significant differences in codon usage patterns of Each virus of Circoviridae.There is much comparability between PCV and its host in their synonymous codon usage, suggesting that the natural selection pressure from the host factor also affect the codon usage patterns of PCV. In particular, PCV genotype II is in synonymous codon usage more similar to pig than to PCV genotype I, which may be one of the most important molecular mechanisms of PCV genotype II to cause disease. The calculations results of the relative abundance of dinucleotides indicate that the composition of dinucleotides also plays a key role in the variation found in synonymous codon usage in PCV. Furthermore, geographic factors, the general average hydrophobicity and the aromaticity may be related to the formation of codon usage patterns of PCV. CONCLUSION: The results of these studies suggest that synonymous codon usage pattern of PCV genome are the result of interaction between mutation pressure and natural selection from its host. The information from this study may not only have theoretical value in understanding the characteristics of synonymous codon usage in PCV genomes, but also have significant value for the molecular evolution of PCV.",2012 Mar 15,"['LIU, Xin-sheng', 'Zhang, Yong-guang', 'Fang, Yu-zhen', 'Wang, Yong-lu']",Virol J,,,True
6848f444e963e825730c6fbcf63b78b65d0efd3d,PMC,Development of a Humanized Antibody with High Therapeutic Potential against Dengue Virus Type 2,http://dx.doi.org/10.1371/journal.pntd.0001636,PMC3341331,22563515,CC BY,"BACKGROUND: Dengue virus (DENV) is a significant public health threat in tropical and subtropical regions of the world. A therapeutic antibody against the viral envelope (E) protein represents a promising immunotherapy for disease control. METHODOLOGY/PRINCIPAL FINDINGS: We generated seventeen novel mouse monoclonal antibodies (mAbs) with high reactivity against E protein of dengue virus type 2 (DENV-2). The mAbs were further dissected using recombinant E protein domain I-II (E-DI-II) and III (E-DIII) of DENV-2. Using plaque reduction neutralization test (PRNT) and mouse protection assay with lethal doses of DENV-2, we identified four serotype-specific mAbs that had high neutralizing activity against DENV-2 infection. Of the four, E-DIII targeting mAb DB32-6 was the strongest neutralizing mAb against diverse DENV-2 strains. Using phage display and virus-like particles (VLPs) we found that residue K310 in the E-DIII A-strand was key to mAb DB32-6 binding E-DIII. We successfully converted DB32-6 to a humanized version that retained potency for the neutralization of DENV-2 and did not enhance the viral infection. The DB32-6 showed therapeutic efficacy against mortality induced by different strains of DENV-2 in two mouse models even in post-exposure trials. CONCLUSIONS/SIGNIFICANCE: We used novel epitope mapping strategies, by combining phage display with VLPs, to identify the important A-strand epitopes with strong neutralizing activity. This study introduced potential therapeutic antibodies that might be capable of providing broad protection against diverse DENV-2 infections without enhancing activity in humans.",2012 May 1,"['Li, Pi-Chun', 'Liao, Mei-Ying', 'Cheng, Ping-Chang', 'Liang, Jian-Jong', 'Liu, I-Ju', 'Chiu, Chien-Yu', 'Lin, Yi-Ling', 'Chang, Gwong-Jen J.', 'Wu, Han-Chung']",PLoS Negl Trop Dis,,,True
1c0ae4beee003ecb59ff15f81ed8f22cd9451353,PMC,"Knowledge, attitudes and practices related to avian influenza among poultry workers in Nepal: a cross sectional study",http://dx.doi.org/10.1186/1471-2334-12-76,PMC3342178,22458535,CC BY,"BACKGROUND: Avian influenza is a considerable threat to global public health. Prevention and control depend on awareness and protective behaviours of the general population as well as high risk-groups. This study aims to explore the knowledge, attitudes and practices related to avian influenza among poultry workers in Nepal. METHODS: The study was based on a cross-sectional study design, using a structured questionnaire administered in face-to-face interviews with 96 poultry workers age 15 and above from the Rupandehi district in Nepal. RESULTS: The majority of respondents were male (80%), mean age was 35 (SD = 11.6). Nearly everybody was aware that AI cases had been detected in Nepal and that poultry workers were at risk for infection. The major sources of AI information were radio, TV and newspapers. Knowledge about preventive measures was high with regard to some behaviours (hand washing), but medium to low with regard to others (using cleaning and disinfecting procedures or protective clothing). Poultry workers who got their information from TV and newspapers and those who were more afraid of contracting AI had higher knowledge than those who did not. Being employed as compared to being an owner of a poultry farm as well as having a high level of knowledge was associated with practising more preventive behaviours. While on one hand many specific government control measures found a high degree of acceptance, a majority of study participants also thought that government control and compensation measures as a whole were insufficient. CONCLUSIONS: The study provides information about knowledge and practices regarding avian influenza among poultry workers in Nepal. It highlights the importance of targeting lack of knowledge as well as structural-material barriers to successfully build preparedness for a major outbreak situation.",2012 Mar 30,"['Neupane, Dinesh', 'Khanal, Vishnu', 'Ghimire, Kamal', 'Aro, Arja R', 'Leppin, Anja']",BMC Infect Dis,,,True
9399460a7a75b8ae8a4f5610fd1ecf05d21d2f17,PMC,Proteomics analysis of differentially expressed proteins in chicken trachea and kidney after infection with the highly virulent and attenuated coronavirus infectious bronchitis virus in vivo,http://dx.doi.org/10.1186/1477-5956-10-24,PMC3342233,22463732,CC BY,"BACKGROUND: Infectious bronchitis virus (IBV) is first to be discovered coronavirus which is probably endemic in all regions with intensive impact on poultry production. In this study, we used two-dimensional gel electrophoresis (2-DE) and two-dimensional fluorescence difference gel electrophoresis (2-DIGE), coupled with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS), to explore the global proteome profiles of trachea and kidney tissues from chicken at different stages infected in vivo with the highly virulent ck/CH/LDL/97I P(5 )strain of infectious bronchitis virus (IBV) and the embryo-passaged, attenuated ck/CH/LDL/97I P(115 )strain. RESULTS: Fifty-eight differentially expressed proteins were identified. Results demonstrated that some proteins which had functions in cytoskeleton organization, anti-oxidative stress, and stress response, showed different change patterns in abundance from chicken infected with the highly virulent ck/CH/LDL/97I P(5 )strain and those given the embryo-passaged, attenuated P(115 )stain. In addition, the dynamic transcriptional alterations of 12 selected proteins were analyzed by the real-time RT-PCR, and western blot analysis confirmed the change in abundance of heat shock proteins (HSP) beta-1, annexin A2, and annexin A5. CONCLUSIONS: The proteomic alterations described here may suggest that these changes to protein expression correlate with IBV virus' virulence in chicken, hence provides valuable insights into the interactions of IBV with its host and may also assist with investigations of the pathogenesis of IBV and other coronavirus infections.",2012 Mar 31,"['Cao, Zhongzan', 'Han, Zongxi', 'Shao, Yuhao', 'Liu, Xiaoli', 'Sun, Junfeng', 'Yu, Demin', 'Kong, Xiangang', 'Liu, Shengwang']",Proteome Sci,,,True
b3deae058a2e470aac4ba8f9425c6150575f1522,PMC,Viral Findings in Adult Hematological Patients with Neutropenia,http://dx.doi.org/10.1371/journal.pone.0036543,PMC3343003,22570724,CC BY,"BACKGROUND: Until recently, viral infections in patients with hematological malignancies were concerns primarily in allogeneic hematopoietic stem cell transplant (HSCT) recipients. During the last years, changed treatment regimens for non-transplanted patients with hematological malignancies have had potential to increase the incidence of viral infections in this group. In this study, we have prospectively investigated the prevalence of a broad range of respiratory viruses in nasopharyngeal aspirate (NPA) as well as viruses that commonly reactivate after allogeneic HSCT. METHODOLOGY/PRINCIPAL FINDINGS: Patients with hematological malignancies and therapy induced neutropenia (n = 159) were screened regarding a broad range of common respiratory viruses in the nasopharynx and for viruses commonly detected in severely immunosuppressed patients in peripheral blood. Quantitative PCR was used for detection of viruses. A viral pathogen was detected in 35% of the patients. The detection rate was rather similar in blood (22%) and NPA (18%) with polyoma BK virus and rhinovirus as dominating pathogens in blood and NPA, respectively. Patients with chronic lymphocytic leukemia (CLL) (p<0.01) and patients with fever (p<0.001) were overrepresented in the virus-positive group. Furthermore, viral findings in NPA were associated with upper respiratory symptoms (URTS) (p<0.0001). CONCLUSIONS/SIGNIFICANCE: Both respiratory viral infections and low titers of viruses in blood from patients with neutropenia were common. Patients with CLL and patients with fever were independently associated to these infections, and viral findings in NPA were associated to URTS indicating active infection. These findings motivate further studies on viruses' impact on this patient category and their potential role as causative agents of fever during neutropenia.",2012 May 3,"['Öhrmalm, Lars', 'Wong, Michelle', 'Aust, Carl', 'Ljungman, Per', 'Norbeck, Oscar', 'Broliden, Kristina', 'Tolfvenstam, Thomas']",PLoS One,,,True
3c988a00ed94308e36a8814b391ead01480efb60,PMC,A Single Polar Residue and Distinct Membrane Topologies Impact the Function of the Infectious Bronchitis Coronavirus E Protein,http://dx.doi.org/10.1371/journal.ppat.1002674,PMC3343006,22570613,CC BY,"The coronavirus E protein is a small membrane protein with a single predicted hydrophobic domain (HD), and has a poorly defined role in infection. The E protein is thought to promote virion assembly, which occurs in the Golgi region of infected cells. It has also been implicated in the release of infectious particles after budding. The E protein has ion channel activity in vitro, although a role for channel activity in infection has not been established. Furthermore, the membrane topology of the E protein is of considerable debate, and the protein may adopt more than one topology during infection. We previously showed that the HD of the infectious bronchitis virus (IBV) E protein is required for the efficient release of infectious virus, an activity that correlated with disruption of the secretory pathway. Here we report that a single residue within the hydrophobic domain, Thr16, is required for secretory pathway disruption. Substitutions of other residues for Thr16 were not tolerated. Mutations of Thr16 did not impact virus assembly as judged by virus-like particle production, suggesting that alteration of secretory pathway and assembly are independent activities. We also examined how the membrane topology of IBV E affected its function by generating mutant versions that adopted either a transmembrane or membrane hairpin topology. We found that a transmembrane topology was required for disrupting the secretory pathway, but was less efficient for virus-like particle production. The hairpin version of E was unable to disrupt the secretory pathway or produce particles. The findings reported here identify properties of the E protein that are important for its function, and provide insight into how the E protein may perform multiple roles during infection.",2012 May 3,"['Ruch, Travis R.', 'Machamer, Carolyn E.']",PLoS Pathog,,,True
31444b90fc581b9b42bfbbb70e4ad4dcf1aca613,PMC,"1,3-Diphenyl-4,5-dihydro-1H-pyrazol-5-one",http://dx.doi.org/10.1107/S1600536812009567,PMC3343981,22589890,CC BY,"In the title pyrazolone derivative, C(15)H(12)N(2)O, the five-membered ring is approximately planar (r.m.s. deviation = 0.018 Å), and the N- and C-bound benzene rings are inclined to this plane [dihedral angles = 21.45 (10) and 6.96 (10)°, respectively] and form a dihedral angle of 20.42 (10)° with each other. Supra­molecular layers are formed in the crystal structure via C—H⋯O and C—H⋯N inter­actions, and these are assembled into double layers by C—H⋯π and π–π inter­actions between the pyrazole and C-bound benzene rings [ring centroid–centroid distance = 3.6476 (12) Å]. The double layers stack along the a axis being connected by π–π inter­actions between the N- and C-bound benzene rings [ring centroid–centroid distance = 3.7718 (12) Å].",2012 Mar 10,"['Baddeley, Thomas C.', 'Wardell, Solange M. S. V.', 'Tiekink, Edward R. T.', 'Wardell, James L.']",Acta Crystallogr Sect E Struct Rep Online,,,True
f6a9c8aafc0ead13250df25ee0f5882f9aeedd76,PMC,Phages and HIV-1: From Display to Interplay,http://dx.doi.org/10.3390/ijms13044727,PMC3344243,22606007,CC BY,"The complex hide-and-seek game between HIV-1 and the host immune system has impaired the development of an efficient vaccine. In addition, the high variability of the virus impedes the long-term control of viral replication by small antiviral drugs. For more than 20 years, phage display technology has been intensively used in the field of HIV-1 to explore the epitope landscape recognized by monoclonal and polyclonal HIV-1-specific antibodies, thereby providing precious data about immunodominant and neutralizing epitopes. In parallel, biopanning experiments with various combinatorial or antibody fragment libraries were conducted on viral targets as well as host receptors to identify HIV-1 inhibitors. Besides these applications, phage display technology has been applied to characterize the enzymatic specificity of the HIV-1 protease. Phage particles also represent valuable alternative carriers displaying various HIV-1 antigens to the immune system and eliciting antiviral responses. This review presents and summarizes the different studies conducted with regard to the nature of phage libraries, target display mode and biopanning procedures.",2012 Apr 13,"['Delhalle, Sylvie', 'Schmit, Jean-Claude', 'Chevigné, Andy']",Int J Mol Sci,,,True
d5a2557d0cb42ffcb93f693d7fa4e70fb817e20b,PMC,The CEA/CD3-Bispecific Antibody MEDI-565 (MT111) Binds a Nonlinear Epitope in the Full-Length but Not a Short Splice Variant of CEA,http://dx.doi.org/10.1371/journal.pone.0036412,PMC3344869,22574157,CC BY,"MEDI-565 (also known as MT111) is a bispecific T-cell engager (BiTE®) antibody in development for the treatment of patients with cancers expressing carcinoembryonic antigen (CEA). MEDI-565 binds CEA on cancer cells and CD3 on T cells to induce T-cell mediated killing of cancer cells. To understand the molecular basis of human CEA recognition by MEDI-565 and how polymorphisms and spliced forms of CEA may affect MEDI-565 activity, we mapped the epitope of MEDI-565 on CEA using mutagenesis and homology modeling approaches. We found that MEDI-565 recognized a conformational epitope in the A2 domain comprised of amino acids 326–349 and 388–410, with critical residues F(326), T(328), N(333), V(388), G(389), P(390), E(392), I(408), and N(410). Two non-synonymous single-nucleotide polymorphisms (SNPs) (rs10407503, rs7249230) were identified in the epitope region, but they are found at low homozygosity rates. Searching the National Center for Biotechnology Information GenBank® database, we further identified a single, previously uncharacterized mRNA splice variant of CEA that lacks a portion of the N-terminal domain, the A1 and B1 domains, and a large portion of the A2 domain. Real-time quantitative polymerase chain reaction analysis of multiple cancers showed widespread expression of full-length CEA in these tumors, with less frequent but concordant expression of the CEA splice variant. Because the epitope was largely absent from the CEA splice variant, MEDI-565 did not bind or mediate T-cell killing of cells solely expressing this form of CEA. In addition, the splice variant did not interfere with MEDI-565 binding or activity when co-expressed with full-length CEA. Thus MEDI-565 may broadly target CEA-positive tumors without regard for expression of the short splice variant of CEA. Together our data suggest that MEDI-565 activity will neither be impacted by SNPs nor by a splice variant of CEA.",2012 May 4,"['Peng, Li', 'Oberst, Michael D.', 'Huang, Jiaqi', 'Brohawn, Philip', 'Morehouse, Chris', 'Lekstrom, Kristen', 'Baeuerle, Patrick A.', 'Wu, Herren', 'Yao, Yihong', 'Coats, Steven R.', 'Dall’Acqua, William', 'Damschroder, Melissa', 'Hammond, Scott A.']",PLoS One,,,True
0867cf1922a634eefb3a3ad07f4dc6c9c94828ea,PMC,High Throughput Screening for Small Molecule Enhancers of the Interferon Signaling Pathway to Drive Next-Generation Antiviral Drug Discovery,http://dx.doi.org/10.1371/journal.pone.0036594,PMC3344904,22574190,CC BY,"Most of current strategies for antiviral therapeutics target the virus specifically and directly, but an alternative approach to drug discovery might be to enhance the immune response to a broad range of viruses. Based on clinical observation in humans and successful genetic strategies in experimental models, we reasoned that an improved interferon (IFN) signaling system might better protect against viral infection. Here we aimed to identify small molecular weight compounds that might mimic this beneficial effect and improve antiviral defense. Accordingly, we developed a cell-based high-throughput screening (HTS) assay to identify small molecules that enhance the IFN signaling pathway components. The assay is based on a phenotypic screen for increased IFN-stimulated response element (ISRE) activity in a fully automated and robust format (Z′>0.7). Application of this assay system to a library of 2240 compounds (including 2160 already approved or approvable drugs) led to the identification of 64 compounds with significant ISRE activity. From these, we chose the anthracycline antibiotic, idarubicin, for further validation and mechanism based on activity in the sub-µM range. We found that idarubicin action to increase ISRE activity was manifest by other members of this drug class and was independent of cytotoxic or topoisomerase inhibitory effects as well as endogenous IFN signaling or production. We also observed that this compound conferred a consequent increase in IFN-stimulated gene (ISG) expression and a significant antiviral effect using a similar dose-range in a cell-culture system inoculated with encephalomyocarditis virus (EMCV). The antiviral effect was also found at compound concentrations below the ones observed for cytotoxicity. Taken together, our results provide proof of concept for using activators of components of the IFN signaling pathway to improve IFN efficacy and antiviral immune defense as well as a validated HTS approach to identify small molecules that might achieve this therapeutic benefit.",2012 May 4,"['Patel, Dhara A.', 'Patel, Anand C.', 'Nolan, William C.', 'Zhang, Yong', 'Holtzman, Michael J.']",PLoS One,,,True
1731adb9524645ed8e10be851313f796f82459c0,PMC,The Coronavirus E Protein: Assembly and Beyond,http://dx.doi.org/10.3390/v4030363,PMC3347032,22590676,CC BY,"The coronavirus E protein is a small membrane protein that has an important role in the assembly of virions. Recent studies have indicated that the E protein has functions during infection beyond assembly, including in virus egress and in the host stress response. Additionally, the E protein has ion channel activity, interacts with host proteins, and may have multiple membrane topologies. The goal of this review is to highlight the properties and functions of the E protein, and speculate on how they may be related.",2012 Mar 8,"['Ruch, Travis R.', 'Machamer, Carolyn E.']",Viruses,,,True
3c9d07cac8fdfacf5199e81f35aa6dd4dc7e49ab,PMC,Feline Immunodeficiency Virus in South America,http://dx.doi.org/10.3390/v4030383,PMC3347033,22590677,CC BY,"The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species. Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV) have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species). Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved. Feline immunodeficiency virus (FIV) causes an immune system disease in domestic cats (Felis catus) involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death. Viruses related to domestic cat FIV occur also in a variety of nondomestic felids. This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs) in South America.",2012 Mar 14,"['Teixeira, Bruno M.', 'Hagiwara, Mitika K.', 'Cruz, Juliano C. M.', 'Hosie, Margaret J.']",Viruses,,,True
c4db01f9d02579bbc25384c6f72a5ce25a4dba0d,PMC,Interplay between Interferon-Mediated Innate Immunity and Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.3390/v4040424,PMC3347317,22590680,CC BY,"Innate immunity is the first line of defense against viral infection, and in turn, viruses have evolved to evade host immune surveillance. As a result, viruses may persist in host and develop chronic infections. Type I interferons (IFN-α/β) are among the most potent antiviral cytokines triggered by viral infections. Porcine reproductive and respiratory syndrome (PRRS) is a disease of pigs that is characterized by negligible induction of type I IFNs and viral persistence for an extended period. For IFN production, RIG-I/MDA5 and JAK-STAT pathways are two major signaling pathways, and recent studies indicate that PRRS virus is armed to modulate type I IFN responses during infection. This review describes the viral strategies for modulation of type I IFN responses. At least three non–structural proteins (Nsp1, Nsp2, and Nsp11) and a structural protein (N nucleocapsid protein) have been identified and characterized to play roles in the IFN suppression and NF-κB pathways. Nsp’s are early proteins while N is a late protein, suggesting that additional signaling pathways may be involved in addition to the IFN pathway. The understanding of molecular bases for virus-mediated modulation of host innate immune signaling will help us design new generation vaccines and control PRRS.",2012 Apr 2,"['Sun, Yan', 'Han, Mingyuan', 'Kim, Chiyong', 'Calvert, Jay G.', 'Yoo, Dongwan']",Viruses,,,True
9751ae6c4cdecf8bfb8934f93a9b2aadf3d4737f,PMC,Daphne Genkwa Sieb. et Zucc. Water-Soluble Extracts Act on Enterovirus 71 by Inhibiting Viral Entry,http://dx.doi.org/10.3390/v4040539,PMC3347322,22590685,CC BY,"Dried flowers of Daphne genkwa Sieb. et Zucc. (Thymelaeaceae) are a Chinese herbal medicine used as an abortifacient with purgative, diuretic and anti-inflammatory activities. However, the activity of this medicine against enteroviral infections has not been investigated. The water-extract of dried buds of D. genkwa Sieb. et Zucc. (DGFW) was examined against various strains of enterovirus 71 (EV71) by neutralization assay, and its initial mode of action was characterized by time-of-addition assay followed by attachment and penetration assays. Pretreatment of DGFW with virus abolished viral replication, indicating that DGFW inhibits EV71 by targeting the virus. GFW exerts its anti-EV71 effects by inhibiting viral entry without producing cytotoxic side effects and thus provides a potential agent for antiviral chemotherapeutics.",2012 Apr 11,"['Chang, Chia-Wen', 'Leu, Yan-Lii', 'Horng, Jim-Tong']",Viruses,,,True
8ba02094773754fa07bf75af55fdddede4129f59,PMC,Daphne Genkwa Sieb. et Zucc. Water-Soluble Extracts Act on Enterovirus 71 by Inhibiting Viral Entry,http://dx.doi.org/10.3390/v4040539,PMC3347322,22590685,CC BY,"Dried flowers of Daphne genkwa Sieb. et Zucc. (Thymelaeaceae) are a Chinese herbal medicine used as an abortifacient with purgative, diuretic and anti-inflammatory activities. However, the activity of this medicine against enteroviral infections has not been investigated. The water-extract of dried buds of D. genkwa Sieb. et Zucc. (DGFW) was examined against various strains of enterovirus 71 (EV71) by neutralization assay, and its initial mode of action was characterized by time-of-addition assay followed by attachment and penetration assays. Pretreatment of DGFW with virus abolished viral replication, indicating that DGFW inhibits EV71 by targeting the virus. GFW exerts its anti-EV71 effects by inhibiting viral entry without producing cytotoxic side effects and thus provides a potential agent for antiviral chemotherapeutics.",2012 Apr 11,"['Chang, Chia-Wen', 'Leu, Yan-Lii', 'Horng, Jim-Tong']",Viruses,,,False
a1add6ab708156c28d4dfa6e0bd825a53c38e418,PMC,"Ready, Set, Fuse! The Coronavirus Spike Protein and Acquisition of Fusion Competence",http://dx.doi.org/10.3390/v4040557,PMC3347323,22590686,CC BY,"Coronavirus-cell entry programs involve virus-cell membrane fusions mediated by viral spike (S) proteins. Coronavirus S proteins acquire membrane fusion competence by receptor interactions, proteolysis, and acidification in endosomes. This review describes our current understanding of the S proteins, their interactions with and their responses to these entry triggers. We focus on receptors and proteases in prompting entry and highlight the type II transmembrane serine proteases (TTSPs) known to activate several virus fusion proteins. These and other proteases are essential cofactors permitting coronavirus infection, conceivably being in proximity to cell-surface receptors and thus poised to split entering spike proteins into the fragments that refold to mediate membrane fusion. The review concludes by noting how understanding of coronavirus entry informs antiviral therapies.",2012 Apr 12,"['Heald-Sargent, Taylor', 'Gallagher, Tom']",Viruses,,,True
71fd4bd89b7dc7a87a4cc7bdcb25be3e444becc4,PMC,Co-circulation of Four Human Coronaviruses (HCoVs) in Queensland Children with Acute Respiratory Tract Illnesses in 2004,http://dx.doi.org/10.3390/v4040637,PMC3347326,22590689,CC BY,"Acute respiratory illnesses (ARIs) with unconfirmed infectious aetiologies peak at different times of the year. Molecular diagnostic assays reduce the number of unconfirmed ARIs compared to serology- or culture-based techniques. Screening of 888 inpatient and outpatient respiratory specimens spanning late autumn through to early spring, 2004, identified the presence of a human coronavirus (HCoV) on 74 occasions (8.3% of all specimens and 26.3% of all respiratory virus detections). Prevalence peaked in August (late winter in the southern hemisphere) when they were detected in 21.9% of specimens tested. HCoV-HKU1 and HCoV-OC43 comprised 82.4% of all HCoVs detected. Positive specimens were used to develop novel reverse transcriptase real-time PCRs (RT-rtPCRs) for HCoV detection. An objective clinical severity score was assigned to each positive HCoV patient. Severity scores were similar to those from a random selection of young children who were positive for respiratory syncytial virus at a different time but from the same specimen population. During the cooler months of 2004, sensitive and specific RT-rtPCRs identified the concurrent circulation of all four HCoVs, a quarter of which co-occurred with another virus and most of which were from children under the age of two years.",2012 Apr 23,"['Mackay, Ian M.', 'Arden, Katherine E.', 'Speicher, David J.', 'O’Neil, Nicholas T.', 'McErlean, Peter K.', 'Greer, Ristan M.', 'Nissen, Michael D.', 'Sloots, Theo P.']",Viruses,,,True
fb24be7627ebce76ab2862e689432a8a0de11343,PMC,Regulation of Immunogen Processing: Signal Sequences and Their Application for the New Generation of DNA-Vaccines,,PMC3347541,22649628,CC BY,"Immunization with naked genes (DNA–immunization) is a perspective modern approach to prophylactic as well as therapeutic vaccination against pathogens, as well as cancer and allergy. A panel of DNA immunogens has been developed, some are already in the clinical trials. However, the immunogenicity of DNA vaccines, specifically of those applied to humans, needs a considerable improvement. There are several approaches to increase DNA vaccine immunogenicity. One approach implies the modifications of the encoded immunogen that change its processing and presentation, and thus the overall pattern of anti–immunogen response. For this, eukaryotic expression vectors are constructed that encode the chimeric proteins composed of the immunogen and specialized targeting or signal sequences. The review describes a number of signals that if fused to immunogen, target it into the predefined subcellular compartments. The review gives examples of their application for DNA–immunization.",2010 Apr,"['Starodubova, E.S.', 'Isaguliants, M.G.', 'Karpov, V.L.']",Acta Naturae,,,True
c62b68c066ad9cbdee5244b9b97e06d7286b2364,PMC,Chinese Medicine Shenfu Injection for Heart Failure: A Systematic Review and Meta-Analysis,http://dx.doi.org/10.1155/2012/713149,PMC3348640,22611430,CC BY,"Objective. Heart failure (HF) is a global public health problem. Early literature studies manifested that Shenfu injection (SFI) is one of the most commonly used traditional Chinese patent medicine for HF in China. This article intended to systematically evaluate the efficacy and safety of SFI for HF. Methods. An extensive search was performed within 6 English and Chinese electronic database up to November 2011. Ninety-nine randomized controlled trails (RCTs) were collected, irrespective of languages. Two authors extracted data and assessed the trial quality independently. RevMan 5.0.2 was used for data analysis. Results. Compared with routine treatment and/or device support, SFI combined with routine treatment and/or device support showed better effect on clinical effect rate, mortality, heart rate, NT-proBNP and 6-minute walk distance. Results in ultrasonic cardiography also showed that SFI combined with routine treatment improved heart function of HF patients. There were no significant difference in blood pressure between SFI and routine treatment groups. Adverse events were reported in thirteen trails with thirteen specific symptoms, while no serious adverse effect was reported. Conclusion. SFI appear to be effective for treating HF. However, further rigorously designed RCTs are warranted because of insufficient methodological rigor in the majority of included trials.",2012 Apr 24,"['Wen-Ting, Song', 'Fa-Feng, Cheng', 'Li, Xu', 'Cheng-Ren, Lin', 'Jian-Xun, Liu']",Evid Based Complement Alternat Med,,,True
f06dde80e1f11939bb7306853ca92a8c9382ede4,PMC,Prevalence and risk factors of feline leukaemia virus and feline immunodeficiency virus in peninsular Malaysia,http://dx.doi.org/10.1186/1746-6148-8-33,PMC3349470,22439903,CC BY,"BACKGROUND: Feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) are major causes of morbidity and mortality in domestic and wild felids. Despite the clinical importance of feline retroviruses and the growing interest in cats as pets, information about FeLV and FIV in Malaysia is presently insufficient to properly advise veterinarians and pet owners. A cross-sectional study was carried out from January 2010 to December 2010 to determine the prevalence and risk factors associated with FeLV and FIV among domestic cats in peninsular Malaysia. Plasma samples were harvested from the blood of 368 domestic cats and screened for evidence of FeLV p27 antigen and FIV antibodies, using an immunochromatographic kit. Additionally, data on cat demographics and health were collected using a structured questionnaire, and were evaluated as potential risk factors for FeLV or FIV status. RESULTS: Of the 368 cats that were evaluated in this study, 12.2% (45/368; 95% CI = 8.88 - 15.58) were positive for FeLV p27 antigen, 31.3%, (115/368; 95% CI = 26.51 - 35.99) were seropositive to FIV antibodies, and 4.3% (16/368; 95% CI = 2.27 - 6.43) had evidence of both viruses. Factors found to significantly increase the risk for FeLV seropositivity include sex, age, behaviour, sickness, and living in a multi-cat household. Seropositive response to FIV was significantly associated with sex, neuter status, age, behaviour, and health status. CONCLUSIONS: The present study indicates that FeLV and FIV are common among domestic cats in peninsular Malaysia, and that factors related to cat demographics and health such as age, sex, behaviour, health status and type of household are important predictors for seropositive status to FeLV or FIV in peninsular Malaysia. High prevalence of FeLV or FIV observed in our study is of concern, in view of the immunosuppressive potentials of the two pathogens. Specific measures for control and prevention such as screening and routine vaccination are needed to ensure that FeLV and FIV are controlled in the cat population of peninsular Malaysia.",2012 Mar 22,"['Bande, Faruku', 'Arshad, Siti Suri', 'Hassan, Latiffah', 'Zakaria, Zunita', 'Sapian, Nurul Asyikin', 'Rahman, Noor Alimah', 'Alazawy, Amer']",BMC Vet Res,,,True
31f33e2c73a467477e3a4a72e6ee128703946fe5,PMC,Factors influencing integration of TB services in general hospitals in two regions of China: a qualitative study,http://dx.doi.org/10.1186/1472-6963-12-21,PMC3349562,22276746,CC BY,"BACKGROUND: In the majority of China, the Centre for Disease Control (CDC) at the county level provides both clinical and public health care for TB cases, with hospitals and other health facilities referring suspected TB cases to the CDC. In recent years, an integrated model has emerged, where the CDC remains the basic management unit for TB control, while a general hospital is designated to provide clinical care for TB patients. This study aims to explore the factors that influence the integration of TB services in general hospitals and generate knowledge to aid the scale-up of integration of TB services in China. METHODS: This study adopted a qualitative approach using interviews from sites in East and West China. Analysis was conducted using a thematic framework approach. RESULTS: The more prosperous site in East China was more coordinated and thus had a better method of resource allocation and more patient-orientated service, compared with the poorer site in the West. The development of public health organizations appeared to influence how effectively integration occurred. An understanding from staff that hospitals had better capacity to treat TB patients than CDCs was a strong rationale for integration. However, the economic and political interests might act as a barrier to effective integration. Both sites shared the same challenges of attracting and retaining a skilled workforce for the TB services. The role of the health bureau was more directive in the Western site, while a more participatory and collaborative approach was adopted in the Eastern site. CONCLUSION: The process of integration identifies similarities and differences between sites in more affluent East China and poorer West China. Integration of TB services in the hospitals needs to address the challenges of stakeholder motivations and resource allocation. Effective inter-organizational collaboration could help to improve the efficiency and quality of TB service. Key words: TB control, service delivery, integration, hospitals, China.",2012 Jan 25,"['Zou, Guanyang', 'Wei, Xiaolin', 'Walley, John D', 'Yin, Jia', 'Sun, Qiang']",BMC Health Serv Res,,,True
cf3abd4ab4ea9d7d602482b62166463db3dffc02,PMC,A systematic review to identify areas of enhancements of pandemic simulation models for operational use at provincial and local levels,http://dx.doi.org/10.1186/1471-2458-12-251,PMC3350431,22463370,CC BY,"BACKGROUND: In recent years, computer simulation models have supported development of pandemic influenza preparedness policies. However, U.S. policymakers have raised several concerns about the practical use of these models. In this review paper, we examine the extent to which the current literature already addresses these concerns and identify means of enhancing the current models for higher operational use. METHODS: We surveyed PubMed and other sources for published research literature on simulation models for influenza pandemic preparedness. We identified 23 models published between 1990 and 2010 that consider single-region (e.g., country, province, city) outbreaks and multi-pronged mitigation strategies. We developed a plan for examination of the literature based on the concerns raised by the policymakers. RESULTS: While examining the concerns about the adequacy and validity of data, we found that though the epidemiological data supporting the models appears to be adequate, it should be validated through as many updates as possible during an outbreak. Demographical data must improve its interfaces for access, retrieval, and translation into model parameters. Regarding the concern about credibility and validity of modeling assumptions, we found that the models often simplify reality to reduce computational burden. Such simplifications may be permissible if they do not interfere with the performance assessment of the mitigation strategies. We also agreed with the concern that social behavior is inadequately represented in pandemic influenza models. Our review showed that the models consider only a few social-behavioral aspects including contact rates, withdrawal from work or school due to symptoms appearance or to care for sick relatives, and compliance to social distancing, vaccination, and antiviral prophylaxis. The concern about the degree of accessibility of the models is palpable, since we found three models that are currently accessible by the public while other models are seeking public accessibility. Policymakers would prefer models scalable to any population size that can be downloadable and operable in personal computers. But scaling models to larger populations would often require computational needs that cannot be handled with personal computers and laptops. As a limitation, we state that some existing models could not be included in our review due to their limited available documentation discussing the choice of relevant parameter values. CONCLUSIONS: To adequately address the concerns of the policymakers, we need continuing model enhancements in critical areas including: updating of epidemiological data during a pandemic, smooth handling of large demographical databases, incorporation of a broader spectrum of social-behavioral aspects, updating information for contact patterns, adaptation of recent methodologies for collecting human mobility data, and improvement of computational efficiency and accessibility.",2012 Mar 30,"['Prieto, Diana M', 'Das, Tapas K', 'Savachkin, Alex A', 'Uribe, Andres', 'Izurieta, Ricardo', 'Malavade, Sharad']",BMC Public Health,,,True
71a82ecd1070ef91422c1ed772c73ad189ea4c0e,PMC,De-Novo Transcriptome Sequencing of a Normalized cDNA Pool from Influenza Infected Ferrets,http://dx.doi.org/10.1371/journal.pone.0037104,PMC3350496,22606336,CC BY,"The ferret is commonly used as a model for studies of infectious diseases. The genomic sequence of this animal model is not yet characterized, and only a limited number of fully annotated cDNAs are currently available in GenBank. The majority of genes involved in innate or adaptive immune response are still lacking, restricting molecular genetic analysis of host response in the ferret model. To enable de novo identification of transcriptionally active ferret genes in response to infection, we performed de-novo transcriptome sequencing of animals infected with H1N1 A/California/07/2009. We also included splenocytes induced with bacterial lipopolysaccharide to allow for identification of transcripts specifically induced by Gram-negative bacteria. We pooled and normalized the cDNA library in order to delimit the risk of sequencing only highly expressed genes. While normalization of the cDNA library removes the possibility of assessing expression changes between individual animals, it has been shown to increase identification of low abundant transcripts. In this study, we identified more than 19000 partial ferret transcripts, including more than 1000 gene orthologs known to be involved in the innate and the adaptive immune response.",2012 May 11,"['Camp, Jeremy V.', 'Svensson, Thomas L.', 'McBrayer, Alexis', 'Jonsson, Colleen B.', 'Liljeström, Peter', 'Bruder, Carl E.']",PLoS One,,,True
bae589aad9c7fe95e859487dc9185968c54d584e,PMC,Interleukin-2 signalling is modulated by a labile disulfide bond in the CD132 chain of its receptor,http://dx.doi.org/10.1098/rsob.110036,PMC3352089,22645657,CC BY,"Certain disulfide bonds present in leucocyte membrane proteins are labile and can be reduced in inflammation. This can cause structural changes that result in downstream functional effects, for example, in integrin activation. Recent studies have shown that a wide range of membrane proteins have labile disulfide bonds including CD132, the common gamma chain of the receptors for several cytokines including interleukin-2 and interleukin-4 (IL-2 and IL-4). The Cys(183)–Cys(232) disulfide bond in mouse CD132 is susceptible to reduction by enzymes such as thioredoxin (TRX), gamma interferon-inducible lysosomal thiolreductase and protein disulfide isomerase, which are commonly secreted during immune activation. The Cys(183)–Cys(232) disulfide bond is also reduced in an in vivo lipopolysaccharide (LPS)-induced acute model of inflammation. Conditions that lead to the reduction of the Cys(183)–Cys(232) disulfide bond in CD132 inhibit proliferation of an IL-2-dependent T cell clone and concomitant inhibition of the STAT-5 signalling pathway. The same reducing conditions had no effect on the proliferation of an IL-2-independent T cell clone, nor did they reduce disulfide bonds in IL-2 itself. We postulate that reduction of the Cys(183)–Cys(232) disulfide in CD132 inhibits IL-2 binding to the receptor complex. Published data show that the Cys(183)–Cys(232) disulfide bond is exposed at the surface of CD132 and in close contact with IL-2 and IL-4 in their respective receptor complexes. In addition, mutants in these Cys residues in human CD132 lead to immunodeficiency and loss of IL-2 binding. These results have wider implications for the regulation of cytokine receptors in general, as their activity can be modulated by a ‘redox regulator’ mechanism caused by the changes in the redox environment that occur during inflammation and activation of the immune system.",2012 Jan,"['Metcalfe, Clive', 'Cresswell, Peter', 'Barclay, A. Neil']",Open Biol,,,True
562b04e742412e61bd4087a2a13734391a988a8f,PMC,A randomized open-label trial on the use of budesonide/formoterol (Symbicort(®)) as an alternative reliever medication for mild to moderate asthmatic attacks,http://dx.doi.org/10.1186/1865-1380-5-16,PMC3352303,22503137,CC BY,"BACKGROUND: Conventionally, a nebulized short-acting β-2 agonist like salbutamol is often used as the reliever in acute exacerbations of asthma. However, recent worldwide respiratory outbreaks discourage routine use of nebulization. Previous studies have shown that combined budesonide/formoterol (Symbicort(®), AstraZeneca) is effective as both a maintenance and reliever anti-asthmatic medication. METHODS: We performed a randomized, open-label study from March until August 2011 to compare the bronchodilatory effects of Symbicort(® )vs. nebulized salbutamol in acute exacerbation of mild to moderate asthmatic attack in an emergency department. Initial objective parameters measured include the oxygen saturation, peak expiratory flow rate (PEFR) and respiratory rate. During clinical reassessment, subjective parameters [i.e., Visual Analog Scale (VAS) and 5-point Likert scale of breathlessness] and the second reading of the objective parameters were measured. For the 5-point Likert scale, the patients were asked to describe their symptom relief as 1, much worse; 2, a little worse; 3, no change; 4, a little better; 5, much better. RESULTS: Out of the total of 32 patients enrolled, 17 patients (53%) were randomized to receive nebulized salbutamol and 15 (47%) to receive Symbicort(®). For both treatment arms, by using paired t- and Wilcoxon signed rank tests, it was shown that there were statistically significant improvements in oxygen saturation, PEFR and respiratory rate within the individual treatment groups (pre- vs. post-treatment). Comparing the effects of Symbicort(® )vs. nebulized salbutamol, the average improvement of oxygen saturation was 1% in both treatment arms (p = 0.464), PEFR 78.67 l/min vs. 89.41 l/min, respectively (p = 0.507), and respiratory rate 2/min vs. 2/min (p = 0.890). For subjective evaluation, all patients reported improvement in the VAS (average 2.45 cm vs. 2.20 cm), respectively (p = 0.765). All patients in both treatment arms reported either ""a little better"" or ""much better"" on the 5-point Likert scale, with none reporting ""no change"" or getting worse. CONCLUSION: This study suggests that there is no statistical difference between using Symbicort(® )vs. nebulized salbutamol as the reliever for the first 15 min post-intervention.",2012 Apr 13,"['Chew, Keng Sheng', 'Kamarudin, Hamizah', 'Hashim, Che Wan']",Int J Emerg Med,,,True
ac0ab279eea38eef425c76172c917fd896417d6c,PMC,The impact of CPR and AED training on healthcare professionals' self-perceived attitudes to performing resuscitation,http://dx.doi.org/10.1186/1757-7241-20-26,PMC3352321,22480164,CC BY,"BACKGROUND: Healthcare professionals have shown concern about performing mouth-to-mouth ventilation due to the risks to themselves with the procedure. However, little is known about healthcare professionals' fears and attitudes to start CPR and the impact of training. OBJECTIVE: To examine whether there were any changes in the attitudes among healthcare professionals to performing CPR from before to after training. METHODS: Healthcare professionals from two Swedish hospitals were asked to answer a questionnaire before and after training. The questions were relating to physical and mental discomfort and attitudes to CPR. Statistical analysis used was generalized McNemar's test. RESULTS: Overall, there was significant improvement in 10 of 11 items, reflecting various aspects of attitudes to CPR. All groups of health care professionals (physicians, nurses, assistant nurses, and ""others"" = physiotherapists, occupational therapists, social welfare officers, psychologists, biomedical analysts) felt more secure in CPR knowledge after education. In other aspects, such as anxiety prior to a possible cardiac arrest, only nurses and assistant nurses improved. The concern about being infected, when performing mouth to mouth ventilation, was reduced with the most marked reduction in physicians (75%; P < 0.001). CONCLUSION: In this hospital-based setting, we found a positive outcome of education and training in CPR concerning healthcare professionals' attitudes to perform CPR. They felt more secure in their knowledge of cardiopulmonary resuscitation. In some aspects of attitudes to resuscitation nurses and assistant nurses appeared to be the groups that were most markedly influenced. The concern of being infected by a disease was low.",2012 Apr 5,"['Källestedt, Marie-Louise Södersved', 'Berglund, Anders', 'Herlitz, Johan', 'Leppert, Jerzy', 'Enlund, Mats']",Scand J Trauma Resusc Emerg Med,,,True
50f6c72d60ef3ae2d2235da9a307942a3f6685fe,PMC,Mechanism of Nucleic Acid Unwinding by SARS-CoV Helicase,http://dx.doi.org/10.1371/journal.pone.0036521,PMC3352918,22615777,CC BY,"The non-structural protein 13 (nsp13) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is a helicase that separates double-stranded RNA (dsRNA) or DNA (dsDNA) with a 5′→3′ polarity, using the energy of nucleotide hydrolysis. We determined the minimal mechanism of helicase function by nsp13. We showed a clear unwinding lag with increasing length of the double-stranded region of the nucleic acid, suggesting the presence of intermediates in the unwinding process. To elucidate the nature of the intermediates we carried out transient kinetic analysis of the nsp13 helicase activity. We demonstrated that the enzyme unwinds nucleic acid in discrete steps of 9.3 base-pairs (bp) each, with a catalytic rate of 30 steps per second. Therefore the net unwinding rate is ∼280 base-pairs per second. We also showed that nsp12, the SARS-CoV RNA-dependent RNA polymerase (RdRp), enhances (2-fold) the catalytic efficiency of nsp13 by increasing the step size of nucleic acid (RNA/RNA or DNA/DNA) unwinding. This effect is specific for SARS-CoV nsp12, as no change in nsp13 activity was observed when foot-and-mouth-disease virus RdRp was used in place of nsp12. Our data provide experimental evidence that nsp13 and nsp12 can function in a concerted manner to improve the efficiency of viral replication and enhance our understanding of nsp13 function during SARS-CoV RNA synthesis.",2012 May 15,"['Adedeji, Adeyemi O.', 'Marchand, Bruno', 'te Velthuis, Aartjan J. W.', 'Snijder, Eric J.', 'Weiss, Susan', 'Eoff, Robert L.', 'Singh, Kamalendra', 'Sarafianos, Stefan G.']",PLoS One,,,True
f3e85a35ab89c9a55eeb83c6e17f881d5c497d82,PMC,Genome-wide host responses against infectious laryngotracheitis virus vaccine infection in chicken embryo lung cells,http://dx.doi.org/10.1186/1471-2164-13-143,PMC3353197,22530940,CC BY,"BACKGROUND: Infectious laryngotracheitis virus (ILTV; gallid herpesvirus 1) infection causes high mortality and huge economic losses in the poultry industry. To protect chickens against ILTV infection, chicken-embryo origin (CEO) and tissue-culture origin (TCO) vaccines have been used. However, the transmission of vaccine ILTV from vaccinated- to unvaccinated chickens can cause severe respiratory disease. Previously, host cell responses against virulent ILTV infections were determined by microarray analysis. In this study, a microarray analysis was performed to understand host-vaccine ILTV interactions at the host gene transcription level. RESULTS: The 44 K chicken oligo microarrays were used, and the results were compared to those found in virulent ILTV infection. Total RNAs extracted from vaccine ILTV infected chicken embryo lung cells at 1, 2, 3 and 4 days post infection (dpi), compared to 0 dpi, were subjected to microarray assay using the two color hybridization method. Data analysis using JMP Genomics 5.0 and the Ingenuity Pathway Analysis (IPA) program showed that 213 differentially expressed genes could be grouped into a number of functional categories including tissue development, cellular growth and proliferation, cellular movement, and inflammatory responses. Moreover, 10 possible gene networks were created by the IPA program to show intermolecular connections. Interestingly, of 213 differentially expressed genes, BMP2, C8orf79, F10, and NPY were expressed distinctly in vaccine ILTV infection when compared to virulent ILTV infection. CONCLUSIONS: Comprehensive knowledge of gene expression and biological functionalities of host factors during vaccine ILTV infection can provide insight into host cellular defense mechanisms compared to those of virulent ILTV.",2012 Apr 24,"['Lee, Jeongyoon', 'Bottje, Walter G', 'Kong, Byung-Whi']",BMC Genomics,,,True
a64792baacb18e3bbfb88eee3a3592c85f04a627,PMC,A Real-Time PCR Assay for Bat SARS-Like Coronavirus Detection and Its Application to Italian Greater Horseshoe Bat Faecal Sample Surveys,http://dx.doi.org/10.1100/2012/989514,PMC3353321,22654650,CC BY,"Bats are source of coronaviruses closely related to the severe acute respiratory syndrome (SARS) virus. Numerous studies have been carried out to identify new bat viruses related to SARS-coronavirus (bat-SARS-like CoVs) using a reverse-transcribed-polymerase chain reaction assay. However, a qualitative PCR could underestimate the prevalence of infection, affecting the epidemiological evaluation of bats in viral ecology. In this work an SYBR Green-real time PCR assay was developed for diagnosing infection with SARS-related coronaviruses from bat guano and was applied as screening tool in a survey carried out on 45 greater horseshoe bats (Rhinolophus ferrumequinum) sampled in Italy in 2009. The assay showed high sensitivity and reproducibility. Its application on bats screening resulted in a prevalence of 42%. This method could be suitable as screening tool in epidemiological surveys about the presence of bat-SARS-like CoVs, consequently to obtain a more realistic scenario of the viral prevalence in the population.",2011 Nov 22,"['Balboni, Andrea', 'Gallina, Laura', 'Palladini, Alessandra', 'Prosperi, Santino', 'Battilani, Mara']",ScientificWorldJournal,,,True
c916747a33f9b4a986dd0e4a4b853db6814b74f9,PMC,A General Strategy to Endow Natural Fusion-protein-Derived Peptides with Potent Antiviral Activity,http://dx.doi.org/10.1371/journal.pone.0036833,PMC3353973,22666328,CC BY,"Fusion between the viral and target cell membranes is an obligatory step for the infectivity of all enveloped virus, and blocking this process is a clinically validated therapeutic strategy. Viral fusion is driven by specialized proteins which, although specific to each virus, act through a common mechanism, the formation of a complex between two heptad repeat (HR) regions. The HR regions are initially separated in an intermediate termed “prehairpin”, which bridges the viral and cell membranes, and then fold onto each other to form a 6-helical bundle (6HB), driving the two membranes to fuse. HR-derived peptides can inhibit viral infectivity by binding to the prehairpin intermediate and preventing its transition to the 6HB. The antiviral activity of HR-derived peptides differs considerably among enveloped viruses. For weak inhibitors, potency can be increased by peptide engineering strategies, but sequence-specific optimization is time-consuming. In seeking ways to increase potency without changing the native sequence, we previously reported that attachment to the HR peptide of a cholesterol group (”cholesterol-tagging”) dramatically increases its antiviral potency, and simultaneously increases its half-life in vivo. We show here that antiviral potency may be increased by combining cholesterol-tagging with dimerization of the HR-derived sequence, using as examples human parainfluenza virus, Nipah virus, and HIV-1. Together, cholesterol-tagging and dimerization may represent strategies to boost HR peptide potency to levels that in some cases may be compatible with in vivo use, possibly contributing to emergency responses to outbreaks of existing or novel viruses.",2012 May 16,"['Pessi, Antonello', 'Langella, Annunziata', 'Capitò, Elena', 'Ghezzi, Silvia', 'Vicenzi, Elisa', 'Poli, Guido', 'Ketas, Thomas', 'Mathieu, Cyrille', 'Cortese, Riccardo', 'Horvat, Branka', 'Moscona, Anne', 'Porotto, Matteo']",PLoS One,,,True
154880a8053db7adb802ae5350656b649496b4a3,PMC,DC-SIGN (CD209) Promoter −336 A/G (rs4804803) Polymorphism Associated with Susceptibility of Kawasaki Disease,http://dx.doi.org/10.1100/2012/634835,PMC3354554,22629172,CC BY,"Kawasaki disease (KD) is characterized by systemic vasculitis of unknown etiology. High-dose intravenous immunoglobulin (IVIG) is the most effective therapy for KD to reduce the prevalence of coronary artery lesion (CAL) formation. Recently, the α2, 6 sialylated IgG was reported to interact with a lectin receptor, specific intracellular adhesion molecule-3 grabbing nonintegrin homolog-related 1 (SIGN-R1) in mice and dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) in human, and to trigger an anti-inflammatory cascade. This study was conducted to investigate whether the polymorphism of DC-SIGN (CD209) promoter −336 A/G (rs4804803) is responsible for susceptibility and CAL formation in KD patients using Custom TaqMan SNP Genotyping Assays. A total of 521 subjects (278 KD patients and 243 controls) were investigated to identify an SNP of rs4804803, and they were studied and showed a significant association between the genotypes and allele frequency of rs4804803 in control subjects and KD patients (P = 0.004 under the dominant model). However, the promoter variant of DC-SIGN gene was not associated with the occurrence of IVIG resistance, CAL formation in KD. The G allele of DC-SIGN promoter −336 (rs4804803) is a risk allele in the development of KD.",2012 May 2,"['Yu, Hong-Ren', 'Chang, Wei-Pin', 'Wang, Lin', 'Lin, Ying-Jui', 'Liang, Chi-Di', 'Yang, Kuender D.', 'Kuo, Chiu-Ming', 'Huang, Yi-Chuan', 'Chang, Wei-Chiao', 'Kuo, Ho-Chang']",ScientificWorldJournal,,,True
704daa0a70b4f0c0ba3c8f723b27396877dca38b,PMC,CD40 Gene Polymorphisms Associated with Susceptibility and Coronary Artery Lesions of Kawasaki Disease in the Taiwanese Population,http://dx.doi.org/10.1100/2012/520865,PMC3354684,22645426,CC BY,"Background. Kawasaki disease (KD) is characterized by systemic vasculitis of unknown etiology. Our previous studies showed expression of CD40 ligand on CD4+ T cells correlated to the coronary artery lesion (CAL) and disease progress in KD. Other studies from Japan suggested the role of CD40L in the pathogenesis of CAL, and this might help explain the excessive number of males affected with KD but cannot be reproduced by Taiwanese population. This study was conducted to investigate the CD40 polymorphism in KD and CAL formation. Methods. A total of 950 subjects (381 KD patients and 569 controls) were investigated to identify 2 tagging single-nucleotide polymorphisms (tSNPs) of CD40 (rs4810485 and rs1535045) by using the TaqMan allelic discrimination assay. Results. A significant association was noted with regards to CD40 tSNPs (rs1535045) between controls and KD patients (P = 0.0405, dominant model). In KD patients, polymorphisms of CD40 (rs4810485) showed significant association with CAL formation (P = 0.0436, recessive model). Haplotype analysis did not yield more significant results between polymorphisms of CD40 and susceptibility/disease activity of KD. Conclusions. This study showed for the first time that polymorphisms of CD40 are associated with susceptibility to KD and CAL formation, in the Taiwanese population.",2012 May 2,"['Kuo, Ho-Chang', 'Chao, Mei-Chyn', 'Hsu, Yu-Wen', 'Lin, Ying-Chi', 'Huang, Ying-Hsien', 'Yu, Hong-Ren', 'Hou, Ming-Feng', 'Liang, Chi-Di', 'Yang, Kuender D.', 'Chang, Wei-Chiao', 'Wang, Chih-Lu']",ScientificWorldJournal,,,True
05eae269e7bd3b7b841a84c02b1c13a670faf012,PMC,The Ubiquitin/Proteasome System Mediates Entry and Endosomal Trafficking of Kaposi's Sarcoma-Associated Herpesvirus in Endothelial Cells,http://dx.doi.org/10.1371/journal.ppat.1002703,PMC3355089,22615563,CC BY,"Ubiquitination, a post-translational modification, mediates diverse cellular functions including endocytic transport of molecules. Kaposi's sarcoma-associated herpesvirus (KSHV), an enveloped herpesvirus, enters endothelial cells primarily through clathrin-mediated endocytosis. Whether ubiquitination and proteasome activity regulates KSHV entry and endocytosis remains unknown. We showed that inhibition of proteasome activity reduced KSHV entry into endothelial cells and intracellular trafficking to nuclei, thus preventing KSHV infection of the cells. Three-dimensional (3-D) analyses revealed accumulation of KSHV particles in a cytoplasmic compartment identified as EEA1+ endosomal vesicles upon proteasome inhibition. KSHV particles are colocalized with ubiquitin-binding proteins epsin and eps15. Furthermore, ubiquitination mediates internalization of both KSHV and one of its receptors integrin β1. KSHV particles are colocalized with activated forms of the E3 ligase c-Cbl. Knock-down of c-Cbl or inhibition of its phosphorylation reduced viral entry and intracellular trafficking, resulting in decreased KSHV infectivity. These results demonstrate that ubiquitination mediates internalization of both KSHV and one of its cognate receptors integrin β1, and identify c-Cbl as a potential E3 ligase that facilitates this process.",2012 May 17,"['Greene, Whitney', 'Zhang, Wei', 'He, Meilan', 'Witt, Colleen', 'Ye, Fengchun', 'Gao, Shou-Jiang']",PLoS Pathog,,,True
9f3ce3644f26781fd3d232942e4b5a36291545b0,PMC,Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1002712,PMC3355090,22615570,CC BY,"Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.",2012 May 17,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Ramachandran, Srividya', 'Ogino, Tomoaki', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Diamond, Michael S.', 'Virgin, Herbert W.', 'Sen, Ganes C.']",PLoS Pathog,,,True
4a94e577fa3d124b70c4734955c91f78fe749993,PMC,Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1002712,PMC3355090,22615570,CC BY,"Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.",2012 May 17,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Ramachandran, Srividya', 'Ogino, Tomoaki', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Diamond, Michael S.', 'Virgin, Herbert W.', 'Sen, Ganes C.']",PLoS Pathog,,,False
2307b2dca802e80426f5ea0026fa5932ff391320,PMC,Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1002712,PMC3355090,22615570,CC BY,"Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.",2012 May 17,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Ramachandran, Srividya', 'Ogino, Tomoaki', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Diamond, Michael S.', 'Virgin, Herbert W.', 'Sen, Ganes C.']",PLoS Pathog,,,False
96eadfbd199d90264168e4ba9009f53259f395be,PMC,Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1002712,PMC3355090,22615570,CC BY,"Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.",2012 May 17,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Ramachandran, Srividya', 'Ogino, Tomoaki', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Diamond, Michael S.', 'Virgin, Herbert W.', 'Sen, Ganes C.']",PLoS Pathog,,,False
0c4b472760655e118f62a389b8208dc724eceab1,PMC,Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1002712,PMC3355090,22615570,CC BY,"Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.",2012 May 17,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Ramachandran, Srividya', 'Ogino, Tomoaki', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Diamond, Michael S.', 'Virgin, Herbert W.', 'Sen, Ganes C.']",PLoS Pathog,,,False
2e2c403d16452b2a2cb0898a7c2fd98f053bc138,PMC,Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1002712,PMC3355090,22615570,CC BY,"Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.",2012 May 17,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Ramachandran, Srividya', 'Ogino, Tomoaki', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Diamond, Michael S.', 'Virgin, Herbert W.', 'Sen, Ganes C.']",PLoS Pathog,,,False
22b1fb1eb3368bf9325c0ee8f8360bf90a68873f,PMC,Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1002712,PMC3355090,22615570,CC BY,"Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.",2012 May 17,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Ramachandran, Srividya', 'Ogino, Tomoaki', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Diamond, Michael S.', 'Virgin, Herbert W.', 'Sen, Ganes C.']",PLoS Pathog,,,False
a1789943e5bf551cedec49e4cbb52a0882b69ea4,PMC,Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1002712,PMC3355090,22615570,CC BY,"Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.",2012 May 17,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Ramachandran, Srividya', 'Ogino, Tomoaki', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Diamond, Michael S.', 'Virgin, Herbert W.', 'Sen, Ganes C.']",PLoS Pathog,,,False
48346dec8180ad8bc1f1bcab9fb95f52d13c920f,PMC,CD200 Receptor Controls Sex-Specific TLR7 Responses to Viral Infection,http://dx.doi.org/10.1371/journal.ppat.1002710,PMC3355091,22615569,CC BY,"Immunological checkpoints, such as the inhibitory CD200 receptor (CD200R), play a dual role in balancing the immune system during microbial infection. On the one hand these inhibitory signals prevent excessive immune mediated pathology but on the other hand they may impair clearance of the pathogen. We studied the influence of the inhibitory CD200-CD200R axis on clearance and pathology in two different virus infection models. We find that lack of CD200R signaling strongly enhances type I interferon (IFN) production and viral clearance and improves the outcome of mouse hepatitis corona virus (MHV) infection, particularly in female mice. MHV clearance is known to be dependent on Toll like receptor 7 (TLR7)-mediated type I IFN production and sex differences in TLR7 responses previously have been reported for humans. We therefore hypothesize that CD200R ligation suppresses TLR7 responses and that release of this inhibition enlarges sex differences in TLR7 signaling. This hypothesis is supported by our findings that in vivo administration of synthetic TLR7 ligand leads to enhanced type I IFN production, particularly in female Cd200(−/−) mice and that CD200R ligation inhibits TLR7 signaling in vitro. In influenza A virus infection we show that viral clearance is determined by sex but not by CD200R signaling. However, absence of CD200R in influenza A virus infection results in enhanced lung neutrophil influx and pathology in females. Thus, CD200-CD200R and sex are host factors that together determine the outcome of viral infection. Our data predict a sex bias in both beneficial and pathological immune responses to virus infection upon therapeutic targeting of CD200-CD200R.",2012 May 17,"['Karnam, Guruswamy', 'Rygiel, Tomasz P.', 'Raaben, Matthijs', 'Grinwis, Guy C. M.', 'Coenjaerts, Frank E.', 'Ressing, Maaike E.', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.', 'Meyaard, Linde']",PLoS Pathog,,,True
dc6666eb8156bd4638809009f795ebd4a7843569,PMC,Immunogenetic Mechanisms Driving Norovirus GII.4 Antigenic Variation,http://dx.doi.org/10.1371/journal.ppat.1002705,PMC3355092,22615565,CC BY,"Noroviruses are the principal cause of epidemic gastroenteritis worldwide with GII.4 strains accounting for 80% of infections. The major capsid protein of GII.4 strains is evolving rapidly, resulting in new epidemic strains with altered antigenic potentials. To test if antigenic drift may contribute to GII.4 persistence, human memory B cells were immortalized and the resulting human monoclonal antibodies (mAbs) characterized for reactivity to a panel of time-ordered GII.4 virus-like particles (VLPs). Reflecting the complex exposure history of the volunteer, human anti-GII.4 mAbs grouped into three VLP reactivity patterns; ancestral (1987–1997), contemporary (2004–2009), and broad (1987–2009). NVB 114 reacted exclusively to the earliest GII.4 VLPs by EIA and blockade. NVB 97 specifically bound and blocked only contemporary GII.4 VLPs, while NBV 111 and 43.9 exclusively reacted with and blocked variants of the GII.4.2006 Minerva strain. Three mAbs had broad GII.4 reactivity. Two, NVB 37.10 and 61.3, also detected other genogroup II VLPs by EIA but did not block any VLP interactions with carbohydrate ligands. NVB 71.4 cross-neutralized the panel of time-ordered GII.4 VLPs, as measured by VLP-carbohydrate blockade assays. Using mutant VLPs designed to alter predicted antigenic epitopes, two evolving, GII.4-specific, blockade epitopes were mapped. Amino acids 294–298 and 368–372 were required for binding NVB 114, 111 and 43.9 mAbs. Amino acids 393–395 were essential for binding NVB 97, supporting earlier correlations between antibody blockade escape and carbohydrate binding variation. These data inform VLP vaccine design, provide a strategy for expanding the cross-blockade potential of chimeric VLP vaccines, and identify an antibody with broadly neutralizing therapeutic potential for the treatment of human disease. Moreover, these data support the hypothesis that GII.4 norovirus evolution is heavily influenced by antigenic variation of neutralizing epitopes and consequently, antibody-driven receptor switching; thus, protective herd immunity is a driving force in norovirus molecular evolution.",2012 May 17,"['Lindesmith, Lisa C.', 'Beltramello, Martina', 'Donaldson, Eric F.', 'Corti, Davide', 'Swanstrom, Jesica', 'Debbink, Kari', 'Lanzavecchia, Antonio', 'Baric, Ralph S.']",PLoS Pathog,,,True
095a46646955ce130f476cabd654f8bd1c0f2cf4,PMC,Immunogenetic Mechanisms Driving Norovirus GII.4 Antigenic Variation,http://dx.doi.org/10.1371/journal.ppat.1002705,PMC3355092,22615565,CC BY,"Noroviruses are the principal cause of epidemic gastroenteritis worldwide with GII.4 strains accounting for 80% of infections. The major capsid protein of GII.4 strains is evolving rapidly, resulting in new epidemic strains with altered antigenic potentials. To test if antigenic drift may contribute to GII.4 persistence, human memory B cells were immortalized and the resulting human monoclonal antibodies (mAbs) characterized for reactivity to a panel of time-ordered GII.4 virus-like particles (VLPs). Reflecting the complex exposure history of the volunteer, human anti-GII.4 mAbs grouped into three VLP reactivity patterns; ancestral (1987–1997), contemporary (2004–2009), and broad (1987–2009). NVB 114 reacted exclusively to the earliest GII.4 VLPs by EIA and blockade. NVB 97 specifically bound and blocked only contemporary GII.4 VLPs, while NBV 111 and 43.9 exclusively reacted with and blocked variants of the GII.4.2006 Minerva strain. Three mAbs had broad GII.4 reactivity. Two, NVB 37.10 and 61.3, also detected other genogroup II VLPs by EIA but did not block any VLP interactions with carbohydrate ligands. NVB 71.4 cross-neutralized the panel of time-ordered GII.4 VLPs, as measured by VLP-carbohydrate blockade assays. Using mutant VLPs designed to alter predicted antigenic epitopes, two evolving, GII.4-specific, blockade epitopes were mapped. Amino acids 294–298 and 368–372 were required for binding NVB 114, 111 and 43.9 mAbs. Amino acids 393–395 were essential for binding NVB 97, supporting earlier correlations between antibody blockade escape and carbohydrate binding variation. These data inform VLP vaccine design, provide a strategy for expanding the cross-blockade potential of chimeric VLP vaccines, and identify an antibody with broadly neutralizing therapeutic potential for the treatment of human disease. Moreover, these data support the hypothesis that GII.4 norovirus evolution is heavily influenced by antigenic variation of neutralizing epitopes and consequently, antibody-driven receptor switching; thus, protective herd immunity is a driving force in norovirus molecular evolution.",2012 May 17,"['Lindesmith, Lisa C.', 'Beltramello, Martina', 'Donaldson, Eric F.', 'Corti, Davide', 'Swanstrom, Jesica', 'Debbink, Kari', 'Lanzavecchia, Antonio', 'Baric, Ralph S.']",PLoS Pathog,,,False
226a0c0674dd9f9ad4a4e90ff6f03decb03457ab,PMC,Induction of GADD34 Is Necessary for dsRNA-Dependent Interferon-β Production and Participates in the Control of Chikungunya Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1002708,PMC3355096,22615568,CC BY,"Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production and tissue protection. However, detection of double-stranded RNAs in virus-infected cells promotes two concomitant and apparently conflicting events. The dsRNA-dependent protein kinase (PKR) phosphorylates translation initiation factor 2-alpha (eIF2α) and inhibits protein synthesis, whereas cytosolic DExD/H box RNA helicases induce expression of type I-IFN and other cytokines. We demonstrate that the phosphatase-1 cofactor, growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), an important component of the unfolded protein response (UPR), is absolutely required for type I-IFN and IL-6 production by mouse embryonic fibroblasts (MEFs) in response to dsRNA. GADD34 expression in MEFs is dependent on PKR activation, linking cytosolic microbial sensing with the ATF4 branch of the UPR. The importance of this link for anti-viral immunity is underlined by the extreme susceptibility of GADD34-deficient fibroblasts and neonate mice to Chikungunya virus infection.",2012 May 17,"['Clavarino, Giovanna', 'Cláudio, Nuno', 'Couderc, Thérèse', 'Dalet, Alexandre', 'Judith, Delphine', 'Camosseto, Voahirana', 'Schmidt, Enrico K.', 'Wenger, Till', 'Lecuit, Marc', 'Gatti, Evelina', 'Pierre, Philippe']",PLoS Pathog,,,True
eff3310317521aed7abe06ef1fa9963ca9d6caf3,PMC,The Adjuvanticity of an O. volvulus-Derived rOv-ASP-1 Protein in Mice Using Sequential Vaccinations and in Non-Human Primates,http://dx.doi.org/10.1371/journal.pone.0037019,PMC3355165,22615877,CC BY,"Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the rOv-ASP-1 adjuvant may also induce anti-self-antibodies. Therefore, it was important to verify that the host responses to self will not affect the adjuvanticity of rOv-ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established rOv-ASP-1's adjuvanticity in mice during the course of two sequential vaccinations using two vaccine model systems: the receptor-binding domain (RBD) of SARS-CoV spike protein and a commercial influenza virus hemagglutinin (HA) vaccine comprised of three virus strains. Moreover, the adjuvanticity of rOv-ASP-1 was retained with an efficacy similar to that obtained when it was used for a first vaccination, even though a high level of anti-rOv-ASP-1 antibodies was present in the sera of mice before the administration of the second vaccine. To further demonstrate its utility as an adjuvant for human use, we also immunized non-human primates (NHPs) with RBD plus rOv-ASP-1 and showed that rOv-ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the rOv-ASP-1 adjuvant did not induce high titer antibodies against self in NHPs. Thus, the present study provided a sound scientific foundation for future strategies in the development of this novel protein adjuvant.",2012 May 17,"['Wang, Jing', 'Tricoche, Nancy', 'Du, Lanying', 'Hunter, Meredith', 'Zhan, Bin', 'Goud, Gaddam', 'Didier, Elizabeth S.', 'Liu, Jing', 'Lu, Lu', 'Marx, Preston A.', 'Jiang, Shibo', 'Lustigman, Sara']",PLoS One,,,True
ff218f343fbca258501ba42368ecbb57660e5a8f,PMC,An Analogue of the Antibiotic Teicoplanin Prevents Flavivirus Entry In Vitro,http://dx.doi.org/10.1371/journal.pone.0037244,PMC3356272,22624001,CC BY,"There is an urgent need for potent inhibitors of dengue virus (DENV) replication for the treatment and/or prophylaxis of infections with this virus. We here report on an aglycon analogue of the antibiotic teicoplanin (code name LCTA-949) that inhibits DENV-induced cytopathic effect (CPE) in a dose-dependent manner. Virus infection was completely inhibited at concentrations that had no adverse effect on the host cells. These findings were corroborated by quantification of viral RNA levels in culture supernatant. Antiviral activity was also observed against other flaviviruses such as the yellow fever virus and the tick-borne encephalitis virus (TBEV). In particular, potent antiviral activity was observed against TBEV. Time-of-drug-addition experiments indicated that LCTA-949 inhibits an early stage in the DENV replication cycle; however, a virucidal effect was excluded. This observation was corroborated by the fact that LCTA-949 lacks activity on DENV subgenomic replicon (that does not encode structural proteins) replication. Using a microsopy-based binding and fusion assay employing DiD-labeled viruses, it was shown that LCTA-949 targets the early stage (binding/entry) of the infection. Moreover, LCTA-949 efficiently inhibits infectivity of DENV particles pre-opsonized with antibodies, thus potentially also inhibiting antibody-dependent enhancement (ADE). In conclusion, LCTA-949 exerts in vitro activity against several flaviviruses and does so (as shown for DENV) by interfering with an early step in the viral replication cycle.",2012 May 18,"['De Burghgraeve, Tine', 'Kaptein, Suzanne J. F.', 'Ayala-Nunez, Nilda V.', 'Mondotte, Juan A.', 'Pastorino, Boris', 'Printsevskaya, Svetlana S.', 'de Lamballerie, Xavier', 'Jacobs, Michael', 'Preobrazhenskaya, Maria', 'Gamarnik, Andrea V.', 'Smit, Jolanda M.', 'Neyts, Johan']",PLoS One,,,True
2a423f15be9162d939e0402df6f74c31ee2e9486,PMC,Viral Infection in Renal Transplant Recipients,http://dx.doi.org/10.1100/2012/820621,PMC3357934,22654630,CC BY,"Viruses are among the most common causes of opportunistic infection after transplantation. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or posttransplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This paper will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens.",2012 May 2,"['Cukuranovic, Jovana', 'Ugrenovic, Sladjana', 'Jovanovic, Ivan', 'Visnjic, Milan', 'Stefanovic, Vladisav']",ScientificWorldJournal,,,True
a466d42cb39e44cacc9d9923ddf169e6a9dad838,PMC,The Time Required to Estimate the Case Fatality Ratio of Influenza Using Only the Tip of an Iceberg: Joint Estimation of the Virulence and the Transmission Potential,http://dx.doi.org/10.1155/2012/978901,PMC3357941,22649483,CC BY,"Estimating the case fatality ratio (CFR) of a novel strain of influenza virus during the early stage of the pandemic is one of key epidemiological tasks to be conducted as rapid research response. Past experience during the epidemics of severe acute respiratory syndrome (SARS) and influenza A (H1N1-2009) posed several technical challenges in estimating the CFR in real time. The present study aimed to develop a simple method to estimate the CFR based on readily available datasets, that is, confirmed cases and deaths, while addressing some of the known technical issues. To assess the reliability and validity of the proposed method, we examined the minimum length of time required for the assigned CFR to be included within the 95% confidence intervals and for the estimated CFR to be below a prespecified cut-off value by means of Monte Carlo simulations. Overall, the smaller the transmission potential was, the longer it took to compare the estimated CFR against the cut-off value. If policymaking and public health response have to be made based on the CFR estimate derived from the proposed method and readily available data, it should be noted that the successful estimation may take longer than a few months.",2012 May 10,"['Ejima, Keisuke', 'Omori, Ryosuke', 'Cowling, Benjamin J.', 'Aihara, Kazuyuki', 'Nishiura, Hiroshi']",Comput Math Methods Med,,,True
cccb1a743e85a745309415410b3101c2ab1b59bb,PMC,Increased Urinary Angiotensin-Converting Enzyme 2 in Renal Transplant Patients with Diabetes,http://dx.doi.org/10.1371/journal.pone.0037649,PMC3358292,22629438,CC BY,"Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be a renoprotective enzyme, since it converts angiotensin (Ang) II to Ang-(1-7). ACE2 has been detected in urine from patients with chronic kidney disease. We measured urinary ACE2 activity and protein levels in renal transplant patients (age 54 yrs, 65% male, 38% diabetes, n = 100) and healthy controls (age 45 yrs, 26% male, n = 50), and determined factors associated with elevated urinary ACE2 in the patients. Urine from transplant subjects was also assayed for ACE mRNA and protein. No subjects were taking inhibitors of the renin-angiotensin system. Urinary ACE2 levels were significantly higher in transplant patients compared to controls (p = 0.003 for ACE2 activity, and p≤0.001 for ACE2 protein by ELISA or western analysis). Transplant patients with diabetes mellitus had significantly increased urinary ACE2 activity and protein levels compared to non-diabetics (p<0.001), while ACE2 mRNA levels did not differ. Urinary ACE activity and protein were significantly increased in diabetic transplant subjects, while ACE mRNA levels did not differ from non-diabetic subjects. After adjusting for confounding variables, diabetes was significantly associated with urinary ACE2 activity (p = 0.003) and protein levels (p<0.001), while female gender was associated with urinary mRNA levels for both ACE2 and ACE. These data indicate that urinary ACE2 is increased in renal transplant recipients with diabetes, possibly due to increased shedding from tubular cells. Urinary ACE2 could be a marker of renal renin-angiotensin system activation in these patients.",2012 May 22,"['Xiao, Fengxia', 'Hiremath, Swapnil', 'Knoll, Greg', 'Zimpelmann, Joseph', 'Srivaratharajah, Kajenny', 'Jadhav, Deepak', 'Fergusson, Dean', 'Kennedy, Chris R. J.', 'Burns, Kevin D.']",PLoS One,,,True
0943374130f5f8474d6d480d4d038615a0e36de3,PMC,Interferon-α Improves Phosphoantigen-Induced Vγ9Vδ2 T-Cells Interferon-γ Production during Chronic HCV Infection,http://dx.doi.org/10.1371/journal.pone.0037014,PMC3358305,22629350,CC BY,"In chronic HCV infection, treatment failure and defective host immune response highly demand improved therapy strategies. Vγ9Vδ2 T-cells may inhibit HCV replication in vitro through IFN-γ release after Phosphoantigen (PhAg) stimulation. The aim of our work was to analyze Vγ9Vδ2 T-cell functionality during chronic HCV infection, studying the role of IFN-α on their function capability. IFN-γ production by Vγ9Vδ2 T-cells was analyzed in vitro in 24 HCV-infected patients and 35 healthy donors (HD) after PhAg stimulation with or without IFN-α. The effect of in vivo PhAg/IFN-α administration on plasma IFN-γ levels was analyzed in M. fascicularis monkeys. A quantitative analysis of IFN-γ mRNA level and stability in Vγ9Vδ2 T-cells was also evaluated. During chronic HCV infection, Vγ9Vδ2 T-cells showed an effector/activated phenotype and were significantly impaired in IFN-γ production. Interestingly, IFN-α was able to improve their IFN-γ response to PhAg both in vitro in HD and HCV-infected patients, and in vivo in Macaca fascicularis primates. Finally, IFN-α increased IFN-γ-mRNA transcription and stability in PhAg-activated Vγ9Vδ2 T-cells. Altogether our results show a functional impairment of Vγ9Vδ2 T-cells during chronic HCV infection that can be partially restored by using IFN-α. A study aimed to evaluate the antiviral impact of PhAg/IFN-α combination may provide new insight in designing possible combined strategies to improve HCV infection treatment outcome.",2012 May 22,"['Cimini, Eleonora', 'Bonnafous, Cécile', 'Bordoni, Veronica', 'Lalle, Eleonora', 'Sicard, Helene', 'Sacchi, Alessandra', 'Berno, Giulia', 'Gioia, Cristiana', 'D’Offizi, Gianpiero', 'Visco Comandini, Ubaldo', 'Vlassi, Chrysoula', 'Capobianchi, Maria Rosaria', 'Martini, Federico', 'Agrati, Chiara']",PLoS One,,,True
bbc89603600968ee09dd4b38c91616f83f7e0bba,PMC,West Nile Virus Infection Causes Endocytosis of a Specific Subset of Tight Junction Membrane Proteins,http://dx.doi.org/10.1371/journal.pone.0037886,PMC3359987,22655077,CC BY,"West Nile virus (WNV) is a blood-borne pathogen that causes systemic infections and serious neurological disease in human and animals. The most common route of infection is mosquito bites and therefore, the virus must cross a number of polarized cell layers to gain access to organ tissue and the central nervous system. Resistance to trans-cellular movement of macromolecules between epithelial and endothelial cells is mediated by tight junction complexes. While a number of recent studies have documented that WNV infection negatively impacts the barrier function of tight junctions, the intracellular mechanism by which this occurs is poorly understood. In the present study, we report that endocytosis of a subset of tight junction membrane proteins including claudin-1 and JAM-1 occurs in WNV infected epithelial and endothelial cells. This process, which ultimately results in lysosomal degradation of the proteins, is dependent on the GTPase dynamin and microtubule-based transport. Finally, infection of polarized cells with the related flavivirus, Dengue virus-2, did not result in significant loss of tight junction membrane proteins. These results suggest that neurotropic flaviviruses such as WNV modulate the host cell environment differently than hemorrhagic flaviviruses and thus may have implications for understanding the molecular basis for neuroinvasion.",2012 May 24,"['Xu, Zaikun', 'Waeckerlin, Regula', 'Urbanowski, Matt D.', 'van Marle, Guido', 'Hobman, Tom C.']",PLoS One,,,True
03d40dcd5d29728439528bd955afcba42bc0c2b9,PMC,"The Epitope and Neutralization Mechanism of AVFluIgG01, a Broad-Reactive Human Monoclonal Antibody against H5N1 Influenza Virus",http://dx.doi.org/10.1371/journal.pone.0038126,PMC3360650,22662275,CC BY,"The continued spread of highly pathogenic avian influenza (HPAI) H5N1 virus underscores the importance of effective antiviral approaches. AVFluIgG01 is a potent and broad-reactive H5N1-neutralizing human monoclonal antibody (mAb) showing great potential for use either for therapeutic purposes or as a basis of vaccine development, but its antigenic epitope and neutralization mechanism have not been finely characterized. In this study, we first demonstrated that AVFluIgG01 targets a novel conformation-dependent epitope in the globular head region of H5N1 hemagglutinin (HA). By selecting mimotopes from a random peptide library in combination with computational algorithms and site-directed mutagenesis, the epitope was mapped to three conserved discontinuous sites (I-III) that are located closely at the three-dimensional structure of HA. Further, we found that this HA1-specific human mAb can efficiently block both virus-receptor binding and post-attachment steps, while its Fab fragment exerts the post-attachment inhibition only. Consistently, AVFluIgG01 could inhibit HA-mediated cell-cell membrane fusion at a dose-dependent manner and block the acquisition of pH-induced protease sensitivity. These results suggest a neutralization mechanism of AVFluIgG01 by simultaneously blocking viral attachment to the receptors on host cells and interfering with HA conformational rearrangements associated with membrane fusion. The presented data provide critical information for developing novel antiviral therapeutics and vaccines against HPAI H5N1 virus.",2012 May 25,"['Cao, Zhiliang', 'Meng, Jiazi', 'Li, Xingxing', 'Wu, Ruiping', 'Huang, Yanxin', 'He, Yuxian']",PLoS One,,,True
b48c4779aeb4c5d68971cc74ac6e6974d39d9195,PMC,PepMapper: A Collaborative Web Tool for Mapping Epitopes from Affinity-Selected Peptides,http://dx.doi.org/10.1371/journal.pone.0037869,PMC3360666,22701536,CC BY,"Epitope mapping from affinity-selected peptides has become popular in epitope prediction, and correspondingly many Web-based tools have been developed in recent years. However, the performance of these tools varies in different circumstances. To address this problem, we employed an ensemble approach to incorporate two popular Web tools, MimoPro and Pep-3D-Search, together for taking advantages offered by both methods so as to give users more options for their specific purposes of epitope-peptide mapping. The combined operation of Union finds as many associated peptides as possible from both methods, which increases sensitivity in finding potential epitopic regions on a given antigen surface. The combined operation of Intersection achieves to some extent the mutual verification by the two methods and hence increases the likelihood of locating the genuine epitopic region on a given antigen in relation to the interacting peptides. The Consistency between Intersection and Union is an indirect sufficient condition to assess the likelihood of successful peptide-epitope mapping. On average from 27 tests, the combined operations of PepMapper outperformed either MimoPro or Pep-3D-Search alone. Therefore, PepMapper is another multipurpose mapping tool for epitope prediction from affinity-selected peptides. The Web server can be freely accessed at: http://informatics.nenu.edu.cn/PepMapper/",2012 May 25,"['Chen, Wenhan', 'Guo, William W.', 'Huang, Yanxin', 'Ma, Zhiqiang']",PLoS One,,,True
09340528717039c904847d959dd4ff0adcc308ed,PMC,Autophagy: More Than a Nonselective Pathway,http://dx.doi.org/10.1155/2012/219625,PMC3362037,22666256,CC BY,"Autophagy is a catabolic pathway conserved among eukaryotes that allows cells to rapidly eliminate large unwanted structures such as aberrant protein aggregates, superfluous or damaged organelles, and invading pathogens. The hallmark of this transport pathway is the sequestration of the cargoes that have to be degraded in the lysosomes by double-membrane vesicles called autophagosomes. The key actors mediating the biogenesis of these carriers are the autophagy-related genes (ATGs). For a long time, it was assumed that autophagy is a bulk process. Recent studies, however, have highlighted the capacity of this pathway to exclusively eliminate specific structures and thus better fulfil the catabolic necessities of the cell. We are just starting to unveil the regulation and mechanism of these selective types of autophagy, but what it is already clearly emerging is that structures targeted to destruction are accurately enwrapped by autophagosomes through the action of specific receptors and adaptors. In this paper, we will briefly discuss the impact that the selective types of autophagy have had on our understanding of autophagy.",2012 May 15,"['Reggiori, Fulvio', 'Komatsu, Masaaki', 'Finley, Kim', 'Simonsen, Anne']",Int J Cell Biol,,,True
24c20b8ab487acad45bb797b2ae0a2a910b31043,PMC,Eicosanoids and Respiratory Viral Infection: Coordinators of Inflammation and Potential Therapeutic Targets,http://dx.doi.org/10.1155/2012/236345,PMC3362132,22665949,CC BY,"Viruses are frequent causes of respiratory infection, and viral respiratory infections are significant causes of hospitalization, morbidity, and sometimes mortality in a variety of patient populations. Lung inflammation induced by infection with common respiratory pathogens such as influenza and respiratory syncytial virus is accompanied by increased lung production of prostaglandins and leukotrienes, lipid mediators with a wide range of effects on host immune function. Deficiency or pharmacologic inhibition of prostaglandin and leukotriene production often results in a dampened inflammatory response to acute infection with a respiratory virus. These mediators may, therefore, serve as appealing therapeutic targets for disease caused by respiratory viral infection.",2012 May 15,"['McCarthy, Mary K.', 'Weinberg, Jason B.']",Mediators Inflamm,,,True
826d74c66a4c9bf882880d1dccc50690c8cdaffb,PMC,Seroepidemiology of Human Bocavirus Infection in Jamaica,http://dx.doi.org/10.1371/journal.pone.0038206,PMC3362556,22666484,CC BY,"BACKGROUND: Human bocavirus (HBoV) is a newly identified human parvovirus. HBoV is associated with upper and lower respiratory tract infections and gastroenteritis in children. Little is known about the seroepidemiology of HBoV in populations in the Caribbean. METHODS: In a cross-sectional study conducted at the University Hospital of the West Indies in Kingston, Jamaica, 287 blood samples were collected from pediatric patients and tested for the presence of HBoV-specific antibody using a virus-like-particle based enzyme-linked immunosorbent assay (ELISA). RESULTS: HBoV-specific antibodies were found to be present in 220/287 (76.7%) of samples collected from the pediatric population. Seroprevalence of HBoV was highest in those ≥2 years old. The seroepidemiological profile suggests that most children are exposed to HBoV during the first two years of life in Jamaica. CONCLUSION: HBoV infection is common in children in Jamaica. HBoV seroprevalence rates in the Caribbean are similar to those previously reported in other areas of the world.",2012 May 29,"['Hustedt, Joshua W.', 'Christie, Celia', 'Hustedt, Madison M.', 'Esposito, Daina', 'Vazquez, Marietta']",PLoS One,,,True
86431a5391ad8d12589fe686d0486cf2a0e912f0,PMC,The Sigma Class Glutathione Transferase from the Liver Fluke Fasciola hepatica,http://dx.doi.org/10.1371/journal.pntd.0001666,PMC3362645,22666515,CC BY,"BACKGROUND: Liver fluke infection of livestock causes economic losses of over US$ 3 billion worldwide per annum. The disease is increasing in livestock worldwide and is a re-emerging human disease. There are currently no commercial vaccines, and only one drug with significant efficacy against adult worms and juveniles. A liver fluke vaccine is deemed essential as short-lived chemotherapy, which is prone to resistance, is an unsustainable option in both developed and developing countries. Protein superfamilies have provided a number of leading liver fluke vaccine candidates. A new form of glutathione transferase (GST) family, Sigma class GST, closely related to a leading Schistosome vaccine candidate (Sm28), has previously been revealed by proteomics in the liver fluke but not functionally characterised. METHODOLOGY/PRINCIPAL FINDINGS: In this manuscript we show that a purified recombinant form of the F. hepatica Sigma class GST possesses prostaglandin synthase activity and influences activity of host immune cells. Immunocytochemistry and western blotting have shown the protein is present near the surface of the fluke and expressed in eggs and newly excysted juveniles, and present in the excretory/secretory fraction of adults. We have assessed the potential to use F. hepatica Sigma class GST as a vaccine in a goat-based vaccine trial. No significant reduction of worm burden was found but we show significant reduction in the pathology normally associated with liver fluke infection. CONCLUSIONS/SIGNIFICANCE: We have shown that F. hepatica Sigma class GST has likely multi-functional roles in the host-parasite interaction from general detoxification and bile acid sequestration to PGD synthase activity.",2012 May 29,"['LaCourse, E. James', 'Perally, Samirah', 'Morphew, Russell M.', 'Moxon, Joseph V.', 'Prescott, Mark', 'Dowling, David J.', ""O'Neill, Sandra M."", 'Kipar, Anja', 'Hetzel, Udo', 'Hoey, Elizabeth', 'Zafra, Rafael', 'Buffoni, Leandro', 'Pérez Arévalo, José', 'Brophy, Peter M.']",PLoS Negl Trop Dis,,,True
72e9038e9738f001e0b050d11f9b05a6376919bc,PMC,Lessons from a one-year hospital-based surveillance of acute respiratory infections in Berlin- comparing case definitions to monitor influenza,http://dx.doi.org/10.1186/1471-2458-12-245,PMC3362781,22452874,CC BY,"BACKGROUND: Surveillance of severe acute respiratory infections (SARI) in sentinel hospitals is recommended to estimate the burden of severe influenza-cases. Therefore, we monitored patients admitted with respiratory infections (RI) in 9 Berlin hospitals from 7.12.2009 to 12.12.2010 according to different case definitions (CD) and determined the proportion of cases with influenza A(H1N1)pdm09 (pH1N1). We compared the sensitivity and specificity of CD for capturing pandemic pH1N1 cases. METHODS: We established an RI-surveillance restricted to adults aged ≤ 65 years within the framework of a pH1N1 vaccine effectiveness study, which required active identification of RI-cases. The hospital information-system was screened daily for newly admitted RI-patients. Nasopharyngeal swabs from consenting patients were tested by PCR for influenza-virus subtypes. Four clinical CD were compared in terms of capturing pH1N1-positives among hospitalized RI-patients by applying sensitivity and specificity analyses. The broadest case definition (CD1) was used for inclusion of RI-cases; the narrowest case definition (CD4) was identical to the SARI case definition recommended by ECDC/WHO. RESULTS: Over the study period, we identified 1,025 RI-cases, of which 283 (28%) met the ECDC/WHO SARI case definition. The percentage of SARI-cases among internal medicine admissions decreased from 3.2% (calendar-week 50-2009) to 0.2% (week 25-2010). Of 354 patients tested by PCR, 20 (6%) were pH1N1-positive. Two case definitions narrower than CD1 but -in contrast to SARI- not requiring shortness of breath yielded the largest areas under the Receiver-Operator-Curve. Heterogeneity of proportions of patients admitted with RI between hospitals was significant. CONCLUSIONS: Comprehensive surveillance of RI cases was feasible in a network of community hospitals. In most settings, several hospitals should be included to ensure representativeness. Although misclassification resulting from failure to obtain symptoms in the hospital information-system cannot be ruled out, a high proportion of hospitalized PCR-positive pH1N1-patients (45%) did not fulfil the SARI case-definition that included shortness of breath or difficulty breathing. Thus, to assess influenza-related disease burden in hospitals, broader, alternative case definitions should be considered.",2012 Mar 27,"['Nachtnebel, Matthias', 'Greutelaers, Benedikt', 'Falkenhorst, Gerhard', 'Jorgensen, Pernille', 'Dehnert, Manuel', 'Schweiger, Brunhilde', 'Träder, Christian', 'Buda, Silke', 'Eckmanns, Tim', 'Wichmann, Ole', 'Hellenbrand, Wiebke']",BMC Public Health,,,True
906902ba01987282a83ec42c2776de9c9bde3834,PMC,Discriminating Active from Latent Tuberculosis in Patients Presenting to Community Clinics,http://dx.doi.org/10.1371/journal.pone.0038080,PMC3364185,22666453,CC BY,"BACKGROUND: Because of the high global prevalence of latent TB infection (LTBI), a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co-existing LTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics. METHODS: Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI. RESULTS: 156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB) were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%), from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82%) and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%). CONCLUSIONS: We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings.",2012 May 30,"['Sandhu, Gurjinder', 'Battaglia, Francesca', 'Ely, Barry K.', 'Athanasakis, Dimitrios', 'Montoya, Rosario', 'Valencia, Teresa', 'Gilman, Robert H.', 'Evans, Carlton A.', 'Friedland, Jon S.', 'Fernandez-Reyes, Delmiro', 'Agranoff, Daniel D.']",PLoS One,,,True
6b47bb3bca780af716c9e986d983f1d2364136c4,PMC,Respiratory viruses in children hospitalized for acute lower respiratory tract infection in Ghana,http://dx.doi.org/10.1186/1743-422X-9-78,PMC3364910,22490115,CC BY,"BACKGROUND: Acute respiratory tract infections are one of the major causes of morbidity and mortality among young children in developing countries. Information on the viral aetiology of acute respiratory infections in developing countries is very limited. The study was done to identify viruses associated with acute lower respiratory tract infection among children less than 5 years. METHOD: Nasopharyngeal samples and blood cultures were collected from children less than 5 years who have been hospitalized for acute lower respiratory tract infection. Viruses and bacteria were identified using Reverse Transcriptase Real-Time Polymerase Chain Reaction and conventional biochemical techniques. RESULTS: Out of 128 patients recruited, 33(25.88%%, 95%CI: 18.5% to 34.2%) were positive for one or more viruses. Respiratory Syncytial Virus (RSV) was detected in 18(14.1%, 95%CI: 8.5% to 21.3%) patients followed by Adenoviruses (AdV) in 13(10.2%, 95%CI: 5.5% to 16.7%), Parainfluenza (PIV type: 1, 2, 3) in 4(3.1%, 95%CI: 0.9% to 7.8%) and influenza B viruses in 1(0.8%, 95%CI: 0.0 to 4.3). Concomitant viral and bacterial co-infection occurred in two patients. There were no detectable significant differences in the clinical signs, symptoms and severity for the various pathogens isolated. A total of 61.1% (22/36) of positive viruses were detected during the rainy season and Respiratory Syncytial Virus was the most predominant. CONCLUSION: The study has demonstrated an important burden of respiratory viruses as major causes of childhood acute respiratory infection in a tertiary health institution in Ghana. The data addresses a need for more studies on viral associated respiratory tract infection.",2012 Apr 10,"['Kwofie, Theophilus B', 'Anane, Yaw A', 'Nkrumah, Bernard', 'Annan, Augustina', 'Nguah, Samuel B', 'Owusu, Michael']",Virol J,,,True
86f450394e3530589eed829b5114c96d87513528,PMC,Longitudinal study on morbidity and mortality in white veal calves in Belgium,http://dx.doi.org/10.1186/1746-6148-8-26,PMC3366893,22414223,CC BY,"BACKGROUND: Mortality and morbidity are hardly documented in the white veal industry, despite high levels of antimicrobial drug use and resistance. The objective of the present study was to determine the causes and epidemiology of morbidity and mortality in dairy, beef and crossbred white veal production. A total of 5853 calves, housed in 15 production cohorts, were followed during one production cycle. Causes of mortality were determined by necropsy. Morbidity was daily recorded by the producers. RESULTS: The total mortality risk was 5,3% and was significantly higher in beef veal production compared to dairy or crossbreds. The main causes of mortality were pneumonia (1.3% of the calves at risk), ruminal disorders (0.7%), idiopathic peritonitis (0.5%), enterotoxaemia (0.5%) and enteritis (0.4%). Belgian Blue beef calves were more likely to die from pneumonia, enterotoxaemia and arthritis. Detection of bovine viral diarrhea virus at necropsy was associated with chronic pneumonia and pleuritis. Of the calves, 25.4% was treated individually and the morbidity rate was 1.66 cases per 1000 calf days at risk. The incidence rate of respiratory disease, diarrhea, arthritis and otitis was 0.95, 0.30, 0.11 and 0.07 cases per 1000 calf days at risk respectively. Morbidity peaked in the first three weeks after arrival and gradually declined towards the end of the production cycle. CONCLUSIONS: The present study provided insights into the causes and epidemiology of morbidity and mortality in white veal calves in Belgium, housed in the most frequent housing system in Europe. The necropsy findings, identified risk periods and differences between production systems can guide both veterinarians and producers towards the most profitable and ethical preventive and therapeutic protocols.",2012 Mar 14,"['Pardon, Bart', 'De Bleecker, Koen', 'Hostens, Miel', 'Callens, Jozefien', 'Dewulf, Jeroen', 'Deprez, Piet']",BMC Vet Res,,,True
a02d5fbeef1d5139b09a0e0017e7fe5e5c885e2c,PMC,Thermostable DNA Polymerase from a Viral Metagenome Is a Potent RT-PCR Enzyme,http://dx.doi.org/10.1371/journal.pone.0038371,PMC3366922,22675552,CC BY,"Viral metagenomic libraries are a promising but previously untapped source of new reagent enzymes. Deep sequencing and functional screening of viral metagenomic DNA from a near-boiling thermal pool identified clones expressing thermostable DNA polymerase (Pol) activity. Among these, 3173 Pol demonstrated both high thermostability and innate reverse transcriptase (RT) activity. We describe the biochemistry of 3173 Pol and report its use in single-enzyme reverse transcription PCR (RT-PCR). Wild-type 3173 Pol contains a proofreading 3′-5′ exonuclease domain that confers high fidelity in PCR. An easier-to-use exonuclease-deficient derivative was incorporated into a PyroScript RT-PCR master mix and compared to one-enzyme (Tth) and two-enzyme (MMLV RT/Taq) RT-PCR systems for quantitative detection of MS2 RNA, influenza A RNA, and mRNA targets. Specificity and sensitivity of 3173 Pol-based RT-PCR were higher than Tth Pol and comparable to three common two-enzyme systems. The performance and simplified set-up make this enzyme a potential alternative for research and molecular diagnostics.",2012 Jun 4,"['Moser, Michael J.', 'DiFrancesco, Robert A.', 'Gowda, Krishne', 'Klingele, Audrey J.', 'Sugar, Darby R.', 'Stocki, Stacy', 'Mead, David A.', 'Schoenfeld, Thomas W.']",PLoS One,,,True
8894267c458259ec6e58acbfad98a82c84519711,PMC,Novel Evidence of HBV Recombination in Family Cluster Infections in Western China,http://dx.doi.org/10.1371/journal.pone.0038241,PMC3366946,22675528,CC BY,"Two hepatitis B virus (HBV) C/D recombinants were isolated from western China. No direct evidence indicates that these new viruses arose as a result of recombination between genotype C and D or a result of convergence. In this study, we search for evidence of intra-individual recombination in the family cluster cases with co-circulation of genotype C, D and C/D recombinants. We studied 68 individuals from 15 families with HBV infections in 2006, identified individuals with mixed HBV genotype co-infections by restriction fragment length polymorphism and proceeded with cloning and DNA sequencing. Recombination signals were detected by RDP3 software and confirmed by split phylogenetic trees. Families with mixed HBV genotype co-infections were resampled in 2007. Three of 15 families had individuals with different HBV genotype co-infections in 2006. One individual (Y2) had a triple infection of HBV genotype C, D and C/D recombinant in 2006, but only genotype D in 2007. Further clonal analysis of this patient indicated that the C/D recombinant was not identical to previously isolated CD1 or CD2, but many novel recombinants with C2, D1 and CD1 were simultaneously found. All parental strains could recombine with each other to form new recombinant in this patient. This indicates that the detectable mixed infection and recombination have a limited time window. Also, as the recombinant nature of HBV precludes the possibility of a simple phylogenetic taxonomy, a new standard may be required for classifying HBV sequences.",2012 Jun 4,"['Zhou, Bin', 'Wang, Zhanhui', 'Yang, Jie', 'Sun, Jian', 'Li, Hua', 'Tanaka, Yasuhito', 'Mizokami, Masashi', 'Hou, Jinlin']",PLoS One,,,True
e81fa612268526f1a649e7d5e70c90dc9c1c4cca,PMC,Identifying Live Bird Markets with the Potential to Act as Reservoirs of Avian Influenza A (H5N1) Virus: A Survey in Northern Viet Nam and Cambodia,http://dx.doi.org/10.1371/journal.pone.0037986,PMC3366999,22675502,CC BY,"Wet markets are common in many parts of the world and may promote the emergence, spread and maintenance of livestock pathogens, including zoonoses. A survey was conducted in order to assess the potential of Vietnamese and Cambodian live bird markets (LBMs) to sustain circulation of highly pathogenic avian influenza virus subtype H5N1 (HPAIV H5N1). Thirty Vietnamese and 8 Cambodian LBMs were visited, and structured interviews were conducted with the market managers and 561 Vietnamese and 84 Cambodian traders. Multivariate and cluster analysis were used to construct a typology of traders based on their poultry management practices. As a result of those practices and large poultry surplus (unsold poultry reoffered for sale the following day), some poultry traders were shown to promote conditions favorable for perpetuating HPAIV H5N1 in LBMs. More than 80% of these traders operated in LBMs located in the most densely populated areas, Ha Noi and Phnom Penh. The profiles of sellers operating at a given LBM could be reliably predicted using basic information about the location and type of market. Consequently, LBMs with the largest combination of risk factors for becoming virus reservoirs could be easily identified, potentially allowing control strategies to be appropriately targeted. These findings are of particular relevance to resource-scarce settings with extensively developed LBM systems, commonly found in South-East Asia.",2012 Jun 4,"['Fournié, Guillaume', 'Guitian, Javier', 'Desvaux, Stéphanie', 'Mangtani, Punam', 'Ly, Sowath', 'Cong, Vu Chi', 'San, Sorn', 'Dung, Do Huu', 'Holl, Davun', 'Pfeiffer, Dirk U.', 'Vong, Sirenda', 'Ghani, Azra C.']",PLoS One,,,True
7d3b1ce33b6c181f3509a9cfa9d6aab1e53c2eaa,PMC,Clinical Relevance and Discriminatory Value of Elevated Liver Aminotransferase Levels for Dengue Severity,http://dx.doi.org/10.1371/journal.pntd.0001676,PMC3367991,22679523,CC BY,"BACKGROUND: Elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is prominent in acute dengue illness. The World Health Organization (WHO) 2009 dengue guidelines defined AST or ALT≥1000 units/liter (U/L) as a criterion for severe dengue. We aimed to assess the clinical relevance and discriminatory value of AST or ALT for dengue hemorrhagic fever (DHF) and severe dengue. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively studied and classified polymerase chain reaction positive dengue patients from 2006 to 2008 treated at Tan Tock Seng Hospital, Singapore according to WHO 1997 and 2009 criteria for dengue severity. Of 690 dengue patients, 31% had DHF and 24% severe dengue. Elevated AST and ALT occurred in 86% and 46%, respectively. Seven had AST or ALT≥1000 U/L. None had acute liver failure but one patient died. Median AST and ALT values were significantly higher with increasing dengue severity by both WHO 1997 and 2009 criteria. However, they were poorly discriminatory between non-severe and severe dengue (e.g., AST area under the receiver operating characteristic [ROC] curve = 0.62; 95% confidence interval [CI]: 0.57–0.67) and between dengue fever (DF) and DHF (AST area under the ROC curve = 0.56; 95% CI: 0.52–0.61). There was significant overlap in AST and ALT values among patients with dengue with or without warning signs and severe dengue, and between those with DF and DHF. CONCLUSIONS: Although aminotransferase levels increased in conjunction with dengue severity, AST or ALT values did not discriminate between DF and DHF or non-severe and severe dengue.",2012 Jun 5,"['Lee, Linda K.', 'Gan, Victor C.', 'Lee, Vernon J.', 'Tan, Adriana S.', 'Leo, Yee Sin', 'Lye, David C.']",PLoS Negl Trop Dis,,,True
a234c5ac982ffc63b7be9d7c1b3473f92849192e,PMC,Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection,http://dx.doi.org/10.1371/journal.pone.0038214,PMC3367995,22679491,CC BY,"Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data.",2012 Jun 5,"['Paquette, Stéphane G.', 'Banner, David', 'Zhao, Zhen', 'Fang, Yuan', 'Huang, Stephen S. H.', 'Leόn, Alberto J.', 'Ng, Derek C. K.', 'Almansa, Raquel', 'Martin-Loeches, Ignacio', 'Ramirez, Paula', 'Socias, Lorenzo', 'Loza, Ana', 'Blanco, Jesus', 'Sansonetti, Paola', 'Rello, Jordi', 'Andaluz, David', 'Shum, Bianche', 'Rubino, Salvatore', 'de Lejarazu, Raul Ortiz', 'Tran, Dat', 'Delogu, Giovanni', 'Fadda, Giovanni', 'Krajden, Sigmund', 'Rubin, Barry B.', 'Bermejo-Martin, Jesús F.', 'Kelvin, Alyson A.', 'Kelvin, David J.']",PLoS One,,,True
d25e47796b1250f545c2b7e5b2dc191eaa3735f0,PMC,Microarray-based method for screening of immunogenic proteins from bacteria,http://dx.doi.org/10.1186/1477-3155-10-12,PMC3368735,22436172,CC BY,"BACKGROUND: Detection of immunogenic proteins remains an important task for life sciences as it nourishes the understanding of pathogenicity, illuminates new potential vaccine candidates and broadens the spectrum of biomarkers applicable in diagnostic tools. Traditionally, immunoscreenings of expression libraries via polyclonal sera on nitrocellulose membranes or screenings of whole proteome lysates in 2-D gel electrophoresis are performed. However, these methods feature some rather inconvenient disadvantages. Screening of expression libraries to expose novel antigens from bacteria often lead to an abundance of false positive signals owing to the high cross reactivity of polyclonal antibodies towards the proteins of the expression host. A method is presented that overcomes many disadvantages of the old procedures. RESULTS: Four proteins that have previously been described as immunogenic have successfully been assessed immunogenic abilities with our method. One protein with no known immunogenic behaviour before suggested potential immunogenicity. We incorporated a fusion tag prior to our genes of interest and attached the expressed fusion proteins covalently on microarrays. This enhances the specific binding of the proteins compared to nitrocellulose. Thus, it helps to reduce the number of false positives significantly. It enables us to screen for immunogenic proteins in a shorter time, with more samples and statistical reliability. We validated our method by employing several known genes from Campylobacter jejuni NCTC 11168. CONCLUSIONS: The method presented offers a new approach for screening of bacterial expression libraries to illuminate novel proteins with immunogenic features. It could provide a powerful and attractive alternative to existing methods and help to detect and identify vaccine candidates, biomarkers and potential virulence-associated factors with immunogenic behaviour furthering the knowledge of virulence and pathogenicity of studied bacteria.",2012 Mar 21,"['Hoppe, Sebastian', 'Bier, Frank F', 'von Nickisch-Rosenegk, Markus']",J Nanobiotechnology,,,True
6694490cc1353addf66465e4d06419ff0b0af753,PMC,Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain,http://dx.doi.org/10.1186/1742-2094-9-50,PMC3368782,22405261,CC BY,"BACKGROUND: Neuropathology caused by acute viral infection of the brain is associated with the development of persistent neurological deficits. Identification of the immune effectors responsible for injuring the brain during acute infection is necessary for the development of therapeutic strategies that reduce neuropathology but maintain immune control of the virus. METHODS: The identity of brain-infiltrating leukocytes was determined using microscopy and flow cytometry at several acute time points following intracranial infection of mice with the Theiler's murine encephalomyelitis virus. Behavioral consequences of immune cell depletion were assessed by Morris water maze. RESULTS: Inflammatory monocytes, defined as CD45(hi)CD11b(++)F4/80(+)Gr1(+)1A8(-), and neutrophils, defined as CD45(hi)CD11b(+++)F4/80(-)Gr1(+)1A8(+), were found in the brain at 12 h after infection. Flow cytometry of brain-infiltrating leukocytes collected from LysM: GFP reporter mice confirmed the identification of neutrophils and inflammatory monocytes in the brain. Microscopy of sections from infected LysM:GFP mice showed that infiltrating cells were concentrated in the hippocampal formation. Immunostaining confirmed that neutrophils and inflammatory monocytes were localized to the hippocampal formation at 12 h after infection. Immunodepletion of inflammatory monocytes and neutrophils but not of neutrophils only resulted in preservation of hippocampal neurons. Immunodepletion of inflammatory monocytes also preserved cognitive function as assessed by the Morris water maze. CONCLUSIONS: Neutrophils and inflammatory monocytes rapidly and robustly responded to Theiler's virus infection by infiltrating the brain. Inflammatory monocytes preceded neutrophils, but both cell types were present in the hippocampal formation at a timepoint that is consistent with a role in triggering hippocampal pathology. Depletion of inflammatory monocytes and neutrophils with the Gr1 antibody resulted in hippocampal neuroprotection and preservation of cognitive function. Specific depletion of neutrophils with the 1A8 antibody failed to preserve neurons, suggesting that inflammatory monocytes are the key effectors of brain injury during acute picornavirus infection of the brain. These effector cells may be important therapeutic targets for immunomodulatory or immunosuppressive therapies aimed at reducing or preventing central nervous system pathology associated with acute viral infection.",2012 Mar 9,"['Howe, Charles L', 'LaFrance-Corey, Reghann G', 'Sundsbak, Rhianna S', 'LaFrance, Stephanie J']",J Neuroinflammation,,,True
ec7e7937ff0f3f8561b73eb8a4d34de49e35e3ff,PMC,HHV-6B Induces IFN-Lambda1 Responses in Cord Plasmacytoid Dendritic Cells through TLR9,http://dx.doi.org/10.1371/journal.pone.0038683,PMC3368904,22701693,CC BY,"Human herpesvirus type 6B (HHV-6B) is a strong inducer of IFN-alpha and has the capacity to promote Th1 responses and block Th2 responses in vitro. In this study we addressed whether inactivated HHV-6B can also induce IFN lambda responses and to what extent interferons alpha and lambda affect Th1/Th2 polarization. We show that inactivated HHV-6B induced IFN-lambda1 (IL-29) but not IFN-lambda2 (IL-28A) responses in plasmacytoid DC and that this induction was mediated through TLR9. We have previously shown that HHV-6B promotes Th1 responses and blocks Th2 responses in both humans and mice. We now show that neutralization of IFN-alpha but not IFN-lambda1 blocked the HHV-6B-induced enhancement of Th1 responses in MLR, but did not affect the HHV-6-induced dampening of Th2 responses. Similarly, blockage of TLR9 counteracted HHV-6Bs effects on the Th1/Th2 balance. In addition, IFN-alpha but not IFN-lambda1 promoted IFN-gamma production and blocked IL-5 and IL-13 production in purified CD4+ T-cells. The lack of effect of IFN-lambda1 correlated with the absence of the IFN-lambda receptor IL-28Ralfa chain on the cell surface of both resting and activated CD4+ T-cells. We conclude that inactivated HHV-6B is a strong inducer of IFN-lambda1 in plasmacytoid DC and that this induction is TLR9-dependent. However, human CD4+ T-cells do not express the IFN-lambda receptor and are refractory to IFN-lambda1 treatment. The HHV-6B-induced alterations in the Th1/Th2 balance are instead mediated mainly through TLR9 and IFN-alpha.",2012 Jun 6,"['Nordström, Inger', 'Eriksson, Kristina']",PLoS One,,,True
349137610648c4aa4a6770afc625a3ea369fb0e3,PMC,Directed Fusion of Mesenchymal Stem Cells with Cardiomyocytes via VSV-G Facilitates Stem Cell Programming,http://dx.doi.org/10.1155/2012/414038,PMC3369562,22701126,CC BY,"Mesenchymal stem cells (MSCs) spontaneously fuse with somatic cells in vivo, albeit rarely, and the fusion products are capable of tissue-specific function (mature trait) or proliferation (immature trait), depending on the microenvironment. That stem cells can be programmed, or somatic cells reprogrammed, in this fashion suggests that stem cell fusion holds promise as a therapeutic approach for the repair of damaged tissues, especially tissues not readily capable of functional regeneration, such as the myocardium. In an attempt to increase the frequency of stem cell fusion and, in so doing, increase the potential for cardiac tissue repair, we expressed the fusogen of the vesicular stomatitis virus (VSV-G) in human MSCs. We found VSV-G expressing MSCs (vMSCs) fused with cardiomyocytes (CMs) and these fusion products adopted a CM-like phenotype and morphology in vitro. In vivo, vMSCs delivered to damaged mouse myocardium via a collagen patch were able to home to the myocardium and fuse to cells within the infarct and peri-infarct region of the myocardium. This study provides a basis for the investigation of the biological impact of fusion of stem cells with CMs in vivo and illustrates how viral fusion proteins might better enable such studies.",2012 May 30,"['Kouris, Nicholas A.', 'Schaefer, Jeremy A.', 'Hatta, Masato', 'Freeman, Brian T.', 'Kamp, Timothy J.', 'Kawaoka, Yoshihiro', 'Ogle, Brenda M.']",Stem Cells Int,,,False
20651c857a793c827bc2d32bbbf6392e8285b84d,PMC,Directed Fusion of Mesenchymal Stem Cells with Cardiomyocytes via VSV-G Facilitates Stem Cell Programming,http://dx.doi.org/10.1155/2012/414038,PMC3369562,22701126,CC BY,"Mesenchymal stem cells (MSCs) spontaneously fuse with somatic cells in vivo, albeit rarely, and the fusion products are capable of tissue-specific function (mature trait) or proliferation (immature trait), depending on the microenvironment. That stem cells can be programmed, or somatic cells reprogrammed, in this fashion suggests that stem cell fusion holds promise as a therapeutic approach for the repair of damaged tissues, especially tissues not readily capable of functional regeneration, such as the myocardium. In an attempt to increase the frequency of stem cell fusion and, in so doing, increase the potential for cardiac tissue repair, we expressed the fusogen of the vesicular stomatitis virus (VSV-G) in human MSCs. We found VSV-G expressing MSCs (vMSCs) fused with cardiomyocytes (CMs) and these fusion products adopted a CM-like phenotype and morphology in vitro. In vivo, vMSCs delivered to damaged mouse myocardium via a collagen patch were able to home to the myocardium and fuse to cells within the infarct and peri-infarct region of the myocardium. This study provides a basis for the investigation of the biological impact of fusion of stem cells with CMs in vivo and illustrates how viral fusion proteins might better enable such studies.",2012 May 30,"['Kouris, Nicholas A.', 'Schaefer, Jeremy A.', 'Hatta, Masato', 'Freeman, Brian T.', 'Kamp, Timothy J.', 'Kawaoka, Yoshihiro', 'Ogle, Brenda M.']",Stem Cells Int,,,True
83447780f68227bd566b75739a926149c96ff3d1,PMC,Design Novel Dual Agonists for Treating Type-2 Diabetes by Targeting Peroxisome Proliferator-Activated Receptors with Core Hopping Approach,http://dx.doi.org/10.1371/journal.pone.0038546,PMC3369836,22685582,CC BY,"Owing to their unique functions in regulating glucose, lipid and cholesterol metabolism, PPARs (peroxisome proliferator-activated receptors) have drawn special attention for developing drugs to treat type-2 diabetes. By combining the lipid benefit of PPAR-alpha agonists (such as fibrates) with the glycemic advantages of the PPAR-gamma agonists (such as thiazolidinediones), the dual PPAR agonists approach can both improve the metabolic effects and minimize the side effects caused by either agent alone, and hence has become a promising strategy for designing effective drugs against type-2 diabetes. In this study, by means of the powerful “core hopping” and “glide docking” techniques, a novel class of PPAR dual agonists was discovered based on the compound GW409544, a well-known dual agonist for both PPAR-alpha and PPAR-gamma modified from the farglitazar structure. It was observed by molecular dynamics simulations that these novel agonists not only possessed the same function as GW409544 did in activating PPAR-alpha and PPAR-gamma, but also had more favorable conformation for binding to the two receptors. It was further validated by the outcomes of their ADME (absorption, distribution, metabolism, and excretion) predictions that the new agonists hold high potential to become drug candidates. Or at the very least, the findings reported here may stimulate new strategy or provide useful insights for discovering more effective dual agonists for treating type-2 diabetes. Since the “core hopping” technique allows for rapidly screening novel cores to help overcome unwanted properties by generating new lead compounds with improved core properties, it has not escaped our notice that the current strategy along with the corresponding computational procedures can also be utilized to find novel and more effective drugs for treating other illnesses.",2012 Jun 7,"['Ma, Ying', 'Wang, Shu-Qing', 'Xu, Wei-Ren', 'Wang, Run-Ling', 'Chou, Kuo-Chen']",PLoS One,,,True
f7204b21080d07e2bb6ffc6fedaa1bf60ba5d67c,PMC,Application of Consensus Scoring and Principal Component Analysis for Virtual Screening against β-Secretase (BACE-1),http://dx.doi.org/10.1371/journal.pone.0038086,PMC3372491,22701601,CC BY,"BACKGROUND: In order to identify novel chemical classes of β-secretase (BACE-1) inhibitors, an alternative scoring protocol, Principal Component Analysis (PCA), was proposed to summarize most of the information from the original scoring functions and re-rank the results from the virtual screening against BACE-1. METHOD: Given a training set (50 BACE-1 inhibitors and 9950 inactive diverse compounds), three rank-based virtual screening methods, individual scoring, conventional consensus scoring and PCA, were judged by the hit number in the top 1% of the ranked list. The docking poses were generated by Surflex, five scoring functions (Surflex_Score, D_Score, G_Score, ChemScore, and PMF_Score) were used for pose extraction. For each pose group, twelve scoring functions (Surflex_Score, D_Score, G_Score, ChemScore, PMF_Score, LigScore1, LigScore2, PLP1, PLP2, jain, Ludi_1, and Ludi_2) were used for the pose rank. For a test set, 113,228 chemical compounds (Sigma-Aldrich® corporate chemical directory) were docked by Surflex, then ranked by the same three ranking methods motioned above to select the potential active compounds for experimental test. RESULTS: For the training set, the PCA approach yielded consistently superior rankings compared to conventional consensus scoring and single scoring. For the test set, the top 20 compounds according to conventional consensus scoring were experimentally tested, no inhibitor was found. Then, we relied on PCA scoring protocol to test another different top 20 compounds and two low micromolar inhibitors (S450588 and 276065) were emerged through the BACE-1 fluorescence resonance energy transfer (FRET) assay. CONCLUSION: The PCA method extends the conventional consensus scoring in a quantitative statistical manner and would appear to have considerable potential for chemical screening applications.",2012 Jun 11,"['Liu, Shu', 'Fu, Rao', 'Zhou, Li-Hua', 'Chen, Sheng-Ping']",PLoS One,,,True
0d0a0fdfcb384b60703d3ea329672f668d7c118e,PMC,Investigation of the Plasmodium falciparum Food Vacuole through Inducible Expression of the Chloroquine Resistance Transporter (PfCRT),http://dx.doi.org/10.1371/journal.pone.0038781,PMC3374814,22719945,CC BY,"Haemoglobin degradation during the erythrocytic life stages is the major function of the food vacuole (FV) of Plasmodium falciparum and the target of several anti-malarial drugs that interfere with this metabolic pathway, killing the parasite. Two multi-spanning food vacuole membrane proteins are known, the multidrug resistance protein 1 (PfMDR1) and Chloroquine Resistance Transporter (PfCRT). Both modulate resistance to drugs that act in the food vacuole. To investigate the formation and behaviour of the food vacuole membrane we have generated inducible GFP fusions of chloroquine sensitive and resistant forms of the PfCRT protein. The inducible expression system allowed us to follow newly-induced fusion proteins, and corroborated a previous report of a direct trafficking route from the ER/Golgi to the food vacuole membrane. These parasites also allowed the definition of a food vacuole compartment in ring stage parasites well before haemozoin crystals were apparent, as well as the elucidation of secondary PfCRT-labelled compartments adjacent to the food vacuole in late stage parasites. We demonstrated that in addition to previously demonstrated Brefeldin A sensitivity, the trafficking of PfCRT is disrupted by Dynasore, a non competitive inhibitor of dynamin-mediated vesicle formation. Chloroquine sensitivity was not altered in parasites over-expressing chloroquine resistant or sensitive forms of the PfCRT fused to GFP, suggesting that the PfCRT does not mediate chloroquine transport as a GFP fusion protein.",2012 Jun 13,"['Ehlgen, Florian', 'Pham, James S.', 'de Koning-Ward, Tania', 'Cowman, Alan F.', 'Ralph, Stuart A.']",PLoS One,,,True
f2a43da3e565ffb44289385ed3c6a4658dc166c1,PMC,"The Acute Environment, Rather than T Cell Subset Pre-Commitment, Regulates Expression of the Human T Cell Cytokine Amphiregulin",http://dx.doi.org/10.1371/journal.pone.0039072,PMC3375254,22720031,CC BY,"Cytokine expression patterns of T cells can be regulated by pre-commitment to stable effector phenotypes, further modification of moderately stable phenotypes, and quantitative changes in cytokine production in response to acute signals. We showed previously that the epidermal growth factor family member Amphiregulin is expressed by T cell receptor-activated mouse CD4 T cells, particularly Th2 cells, and helps eliminate helminth infection. Here we report a detailed analysis of the regulation of Amphiregulin expression by human T cell subsets. Signaling through the T cell receptor induced Amphiregulin expression by most or all T cell subsets in human peripheral blood, including naive and memory CD4 and CD8 T cells, Th1 and Th2 in vitro T cell lines, and subsets of memory CD4 T cells expressing several different chemokine receptors and cytokines. In these different T cell types, Amphiregulin synthesis was inhibited by an antagonist of protein kinase A, a downstream component of the cAMP signaling pathway, and enhanced by ligands that increased cAMP or directly activated protein kinase A. Prostaglandin E2 and adenosine, natural ligands that stimulate adenylyl cyclase activity, also enhanced Amphiregulin synthesis while reducing synthesis of most other cytokines. Thus, in contrast to mouse T cells, Amphiregulin synthesis by human T cells is regulated more by acute signals than pre-commitment of T cells to a particular cytokine pattern. This may be appropriate for a cytokine more involved in repair than attack functions during most inflammatory responses.",2012 Jun 14,"['Qi, Yilin', 'Operario, Darwin J.', 'Georas, Steve N.', 'Mosmann, Tim R.']",PLoS One,,,True
6d12d0dd222c803e8a4e4f3e516d5feecd103358,PMC,Two Glycosylation Sites in H5N1 Influenza Virus Hemagglutinin That Affect Binding Preference by Computer-Based Analysis,http://dx.doi.org/10.1371/journal.pone.0038794,PMC3375263,22719948,CC BY,"Increasing numbers of H5N1 influenza viruses (IVs) are responsible for human deaths, especially in North Africa and Southeast Asian. The binding of hemagglutinin (HA) on the viral surface to host sialic acid (SA) receptors is a requisite step in the infection process. Phylogenetic analysis reveals that H5N1 viruses can be divided into 10 clades based on their HA sequences, with most human IVs centered from clade 1 and clade 2.1 to clade 2.3. Protein sequence alignment in various clades indicates the high conservation in the receptor-binding domains (RBDs) is essential for binding with the SA receptor. Two glycosylation sites, 158N and 169N, also participate in receptor recognition. In the present work, we attempted to construct a serial H5N1 HA models including diverse glycosylated HAs to simulate the binding process with various SA receptors in silico. As the SA-α-2,3-Gal and SA-α-2,6-Gal receptor adopted two distinctive topologies, straight and fishhook-like, respectively, the presence of N-glycans at 158N would decrease the affinity of HA for all of the receptors, particularly SA-α-2,6-Gal analogs. The steric clashes of the huge glycans shown at another glycosylation site, 169N, located on an adjacent HA monomer, would be more effective in preventing the binding of SA-α-2,3-Gal analogs.",2012 Jun 14,"['Chen, Wentian', 'Sun, Shisheng', 'Li, Zheng']",PLoS One,,,True
6d1a2055895ffdcdf57aabcaf436f176b1650c50,PMC,Characterization of Human Coronavirus Etiology in Chinese Adults with Acute Upper Respiratory Tract Infection by Real-Time RT-PCR Assays,http://dx.doi.org/10.1371/journal.pone.0038638,PMC3376151,22719912,CC BY,"BACKGROUND: In addition to SARS associated coronaviruses, 4 non-SARS related human coronaviruses (HCoVs) are recognized as common respiratory pathogens. The etiology and clinical impact of HCoVs in Chinese adults with acute upper respiratory tract infection (URTI) needs to be characterized systematically by molecular detection with excellent sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we detected 4 non-SARS related HCoV species by real-time RT-PCR in 981 nasopharyngeal swabs collected from March 2009 to February 2011. All specimens were also tested for the presence of other common respiratory viruses and newly identified viruses, human metapneumovirus (hMPV) and human bocavirus (HBoV). 157 of the 981 (16.0%) nasopharyngeal swabs were positive for HCoVs. The species detected were 229E (96 cases, 9.8%), OC43 (42 cases, 4.3%), HKU1 (16 cases, 1.6%) and NL63 (11 cases, 1.1%). HCoV-229E was circulated in 21 of the 24 months of surveillance. The detection rates for both OC43 and NL63 were showed significantly year-to-year variation between 2009/10 and 2010/11, respectively (P<0.001 and P = 0.003), and there was a higher detection frequency of HKU1 in patients aged over 60 years (P = 0.03). 48 of 157(30.57%) HCoV positive patients were co-infected. Undifferentiated human rhinoviruses and influenza (Flu) A were the most common viruses detected (more than 35%) in HCoV co-infections. Respiratory syncytial virus (RSV), human parainfluenza virus (PIV) and HBoV were detected in very low rate (less than 1%) among adult patients with URTI. CONCLUSIONS/SIGNIFICANCE: All 4 non-SARS-associated HCoVs were more frequently detected by real-time RT-PCR assay in adults with URTI in Beijing and HCoV-229E led to the most prevalent infection. Our study also suggested that all non-SARS-associated HCoVs contribute significantly to URTI in adult patients in China.",2012 Jun 15,"['Lu, Roujian', 'Yu, Xiaoyan', 'Wang, Wen', 'Duan, Xijie', 'Zhang, Linglin', 'Zhou, Weimin', 'Xu, Jin', 'Xu, Lingjie', 'Hu, Qin', 'Lu, Jianxin', 'Ruan, Li', 'Wang, Zhong', 'Tan, Wenjie']",PLoS One,,,True
acb470a7f8d734e4f257454a90cbb1d933d8bebf,PMC,UNC93B1 Mediates Innate Inflammation and Antiviral Defense in the Liver during Acute Murine Cytomegalovirus Infection,http://dx.doi.org/10.1371/journal.pone.0039161,PMC3377622,22723955,CC BY,"Antiviral defense in the liver during acute infection with the hepatotropic virus murine cytomegalovirus (MCMV) involves complex cytokine and cellular interactions. However, the mechanism of viral sensing in the liver that promotes these cytokine and cellular responses has remained unclear. Studies here were undertaken to investigate the role of nucleic acid-sensing Toll-like receptors (TLRs) in initiating antiviral immunity in the liver during infection with MCMV. We examined the host response of UNC93B1 mutant mice, which do not signal properly through TLR3, TLR7 and TLR9, to acute MCMV infection to determine whether liver antiviral defense depends on signaling through these molecules. Infection of UNC93B1 mutant mice revealed reduced production of systemic and liver proinflammatory cytokines including IFN-α, IFN-γ, IL-12 and TNF-α when compared to wild-type. UNC93B1 deficiency also contributed to a transient hepatitis later in acute infection, evidenced by augmented liver pathology and elevated systemic alanine aminotransferase levels. Moreover, viral clearance was impaired in UNC93B1 mutant mice, despite intact virus-specific CD8+ T cell responses in the liver. Altogether, these results suggest a combined role for nucleic acid-sensing TLRs in promoting early liver antiviral defense during MCMV infection.",2012 Jun 18,"['Crane, Meredith J.', 'Gaddi, Pamela J.', 'Salazar-Mather, Thais P.']",PLoS One,,,True
eff26d8739498efca2d32fe2e66cdbebf0569c50,PMC,Bioinformatics analysis of rabbit haemorrhagic disease virus genome,http://dx.doi.org/10.1186/1743-422X-8-494,PMC3377956,22044910,CC BY,"BACKGROUND: Rabbit haemorrhagic disease virus (RHDV), as the pathogeny of Rabbit haemorrhagic disease, can cause a highly infectious and often fatal disease only affecting wild and domestic rabbits. Recent researches revealed that it, as one number of the Caliciviridae, has some specialties in its genome, its reproduction and so on. RESULTS: In this report, we firstly analyzed its genome and two open reading frameworks (ORFs) from this aspect of codon usage bias. Our researches indicated that mutation pressure rather than natural is the most important determinant in RHDV with high codon bias, and the codon usage bias is nearly contrary between ORF1 and ORF2, which is maybe one of factors regulating the expression of VP60 (encoding by ORF1) and VP10 (encoding by ORF2). Furthermore, negative selective constraints on the RHDV whole genome implied that VP10 played an important role in RHDV lifecycle. CONCLUSIONS: We conjectured that VP10 might be beneficial for the replication, release or both of virus by inducing infected cell apoptosis initiate by RHDV. According to the results of the principal component analysis for ORF2 of RSCU, we firstly separated 30 RHDV into two genotypes, and the ENC values indicated ORF1 and ORF2 were independent among the evolution of RHDV.",2011 Nov 1,"['Tian, Xiao-ting', 'Li, Bao-yu', 'Zhang, Liang', 'Jiao, Wen-qiang', 'Liu, Ji-xing']",Virol J,,,True
123683340d6d91bf7251d4b91b7503f907dd56cc,PMC,Oligonucleotide Based Magnetic Bead Capture of Onchocerca volvulus DNA for PCR Pool Screening of Vector Black Flies,http://dx.doi.org/10.1371/journal.pntd.0001712,PMC3378604,22724041,CC BY,"BACKGROUND: Entomological surveys of Simulium vectors are an important component in the criteria used to determine if Onchocerca volvulus transmission has been interrupted and if focal elimination of the parasite has been achieved. However, because infection in the vector population is quite rare in areas where control has succeeded, large numbers of flies need to be examined to certify transmission interruption. Currently, this is accomplished through PCR pool screening of large numbers of flies. The efficiency of this process is limited by the size of the pools that may be screened, which is in turn determined by the constraints imposed by the biochemistry of the assay. The current method of DNA purification from pools of vector black flies relies upon silica adsorption. This method can be applied to screen pools containing a maximum of 50 individuals (from the Latin American vectors) or 100 individuals (from the African vectors). METHODOLOGY/PRINCIPAL FINDINGS: We have evaluated an alternative method of DNA purification for pool screening of black flies which relies upon oligonucleotide capture of Onchocerca volvulus genomic DNA from homogenates prepared from pools of Latin American and African vectors. The oligonucleotide capture assay was shown to reliably detect one O. volvulus infective larva in pools containing 200 African or Latin American flies, representing a two-four fold improvement over the conventional assay. The capture assay requires an equivalent amount of technical time to conduct as the conventional assay, resulting in a two-four fold reduction in labor costs per insect assayed and reduces reagent costs to $3.81 per pool of 200 flies, or less than $0.02 per insect assayed. CONCLUSIONS/SIGNIFICANCE: The oligonucleotide capture assay represents a substantial improvement in the procedure used to detect parasite prevalence in the vector population, a major metric employed in the process of certifying the elimination of onchocerciasis.",2012 Jun 19,"['Gopal, Hemavathi', 'Hassan, Hassan K.', 'Rodríguez-Pérez, Mario A.', 'Toé, Laurent D.', 'Lustigman, Sara', 'Unnasch, Thomas R.']",PLoS Negl Trop Dis,,,True
68011fab7fc7a4d29797a161cb32d21ffd2a2ea7,PMC,Prediction and Identification of T Cell Epitopes in the H5N1 Influenza Virus Nucleoprotein in Chicken,http://dx.doi.org/10.1371/journal.pone.0039344,PMC3379973,22745738,CC BY,"T cell epitopes can be used for the accurate monitoring of avian influenza virus (AIV) immune responses and the rational design of vaccines. No T cell epitopes have been previously identified in the H5N1 AIV virus nucleoprotein (NP) in chickens. For the first time, this study used homology modelling techniques to construct three-dimensional structures of the peptide-binding domains of chicken MHC class Ι molecules for four commonly encountered unique haplotypes, i.e., B4, B12, B15, and B19. H5N1 AIV NP was computationally parsed into octapeptides or nonapeptides according to the peptide-binding motifs of MHC class I molecules of the B4, B12, B15 and B19 haplotypes. Seventy-five peptide sequences were modelled and their MHC class I molecule-binding abilities were analysed by molecular docking. Twenty-five peptides (Ten for B4, six for B12, two for B15, and seven for B19) were predicted to be potential T cell epitopes in chicken. Nine of these peptides and one unrelated peptide were manually synthesized and their T cell responses were tested in vitro. Spleen lymphocytes were collected from SPF chickens that had been immunised with a NP-expression plasmid, pCAGGS-NP, and they were stimulated using the synthesized peptides. The secretion of chicken IFN-γ and the proliferation of CD8(+) T cells were tested using an ELISA kit and flow cytometry, respectively. The significant secretion of chicken IFN-γ and proliferation of CD8(+) T lymphocytes increased by 13.7% and 11.9% were monitored in cells stimulated with peptides NP(89–97) and NP(198–206), respectively. The results indicate that peptides NP(89–97) (PKKTGGPIY) and NP(198–206) (KRGINDRNF) are NP T cell epitopes in chicken of certain haplotypes. The method used in this investigation is applicable to predicting T cell epitopes for other antigens in chicken, while this study also extends our understanding of the mechanisms of the immune response to AIV in chicken.",2012 Jun 20,"['Hou, Yanxia', 'Guo, Yingying', 'Wu, Chunyan', 'Shen, Nan', 'Jiang, Yongping', 'Wang, Jingfei']",PLoS One,,,True
4241f93b9e7128d98e8b1e81a410999283bc3599,PMC,Model Selection in Time Series Studies of Influenza-Associated Mortality,http://dx.doi.org/10.1371/journal.pone.0039423,PMC3380027,22745751,CC BY,"BACKGROUND: Poisson regression modeling has been widely used to estimate influenza-associated disease burden, as it has the advantage of adjusting for multiple seasonal confounders. However, few studies have discussed how to judge the adequacy of confounding adjustment. This study aims to compare the performance of commonly adopted model selection criteria in terms of providing a reliable and valid estimate for the health impact of influenza. METHODS: We assessed four model selection criteria: quasi Akaike information criterion (QAIC), quasi Bayesian information criterion (QBIC), partial autocorrelation functions of residuals (PACF), and generalized cross-validation (GCV), by separately applying them to select the Poisson model best fitted to the mortality datasets that were simulated under the different assumptions of seasonal confounding. The performance of these criteria was evaluated by the bias and root-mean-square error (RMSE) of estimates from the pre-determined coefficients of influenza proxy variable. These four criteria were subsequently applied to an empirical hospitalization dataset to confirm the findings of simulation study. RESULTS: GCV consistently provided smaller biases and RMSEs for the influenza coefficient estimates than QAIC, QBIC and PACF, under the different simulation scenarios. Sensitivity analysis of different pre-determined influenza coefficients, study periods and lag weeks showed that GCV consistently outperformed the other criteria. Similar results were found in applying these selection criteria to estimate influenza-associated hospitalization. CONCLUSIONS: GCV criterion is recommended for selection of Poisson models to estimate influenza-associated mortality and morbidity burden with proper adjustment for confounding. These findings shall help standardize the Poisson modeling approach for influenza disease burden studies.",2012 Jun 20,"['Wang, Xi-Ling', 'Yang, Lin', 'Chan, King-Pan', 'Chiu, Susan S.', 'Chan, Kwok-Hung', 'Peiris, J. S. Malik', 'Wong, Chit-Ming']",PLoS One,,,True
8d03e1689613cf8af353a27d62adaf44e1b20e67,PMC,Evolutionary Responses to a Constructed Niche: Ancient Mesoamericans as a Model of Gene-Culture Coevolution,http://dx.doi.org/10.1371/journal.pone.0038862,PMC3380856,22768049,CC BY,"Culture and genetics rely on two distinct but not isolated transmission systems. Cultural processes may change the human selective environment and thereby affect which individuals survive and reproduce. Here, we evaluated whether the modes of subsistence in Native American populations and the frequencies of the ABCA1*Arg230Cys polymorphism were correlated. Further, we examined whether the evolutionary consequences of the agriculturally constructed niche in Mesoamerica could be considered as a gene-culture coevolution model. For this purpose, we genotyped 229 individuals affiliated with 19 Native American populations and added data for 41 other Native American groups (n = 1905) to the analysis. In combination with the SNP cluster of a neutral region, this dataset was then used to unravel the scenario involved in 230Cys evolutionary history. The estimated age of 230Cys is compatible with its origin occurring in the American continent. The correlation of its frequencies with the archeological data on Zea pollen in Mesoamerica/Central America, the neutral coalescent simulations, and the F(ST)-based natural selection analysis suggest that maize domestication was the driving force in the increase in the frequencies of 230Cys in this region. These results may represent the first example of a gene-culture coevolution involving an autochthonous American allele.",2012 Jun 21,"['Hünemeier, Tábita', 'Amorim, Carlos Eduardo Guerra', 'Azevedo, Soledad', 'Contini, Veronica', 'Acuña-Alonzo, Víctor', 'Rothhammer, Francisco', 'Dugoujon, Jean-Michel', 'Mazières, Stephane', 'Barrantes, Ramiro', 'Villarreal-Molina, María Teresa', 'Paixão-Côrtes, Vanessa Rodrigues', 'Salzano, Francisco M.', 'Canizales-Quinteros, Samuel', 'Ruiz-Linares, Andres', 'Bortolini, Maria Cátira']",PLoS One,,,True
6c0431081c9d7d41d0efddd87fb0244b401ef67c,PMC,"Vulnerability, equity and universal coverage – a concept note",http://dx.doi.org/10.1186/1471-2458-12-S1-S2,PMC3381707,22992314,CC BY,,2012 Jun 22,"['Allotey, Pascale', 'Verghis, Sharuna', 'Alvarez-Castillo, Fatima', 'Reidpath, Daniel D']",BMC Public Health,,,True
687dd2bd2a0f74f0ef9383f75fb1147e28dfe1d6,PMC,"Differential Seroprevalence of Human Bocavirus Species 1-4 in Beijing, China",http://dx.doi.org/10.1371/journal.pone.0039644,PMC3382199,22761854,CC BY,"BACKGROUND: Four species of human bocaviruses (HBoV1-4) have been identified based on phylogenetic analysis since its first report in 2005. HBoV1 has been associated with respiratory disease, whereas HBoV2-4 are mainly detected in enteric infections. Although the prevalence of HBoVs in humans has been studied in some regions, it has not been well addressed globally. METHODOLOGY/PRINCIPAL FINDINGS: Cross-reactivity of anti-VP2 antibodies was detected between HBoV1, 2, 3, and 4 in mouse and human serum. The prevalence of specific anti-VP2 IgG antibodies against HBoV1-4 was determined in different age groups of healthy individuals aged 0-70 years old in Beijing, China, using a competition ELISA assay based on virus-like particles of HBoV1-4. The seroprevalence of HBoV1-4 was 50%, 36.9%, 28.7%, and 0.8%, respectively, in children aged 0-14 years (n = 244); whereas the seroprevalence of HBoV1-4 was 66.9%, 49.3%, 38.7% and 1.4%, respectively, in healthy adults (≥15 years old; n = 142). The seropositive rate of HBoV1 was higher than that of HBoV2, HBoV3, and HBoV4 in individuals older than 0.5 years. Furthermore, IgG seroconversion of HBoV1 (10/31, 32.3%), HBoV2 (8/31, 25.8%), and HBoV3 (2/31, 6.5%) was found in paired sera collected from children with respiratory tract infections who were positive for HBoV1 according to PCR analysis. CONCLUSIONS/SIGNIFICANCE: Our data indicate that HBoV1 is more prevalent than HBoV2, HBoV3, and HBoV4 in the population we sampled in Beijing, China, suggesting that HBoV species may play differential roles in disease.",2012 Jun 22,"['Guo, Li', 'Wang, Yaying', 'Zhou, Hongli', 'Wu, Chao', 'Song, Jingdong', 'Li, Jianguo', 'Paranhos-Baccalà, Gláucia', 'Vernet, Guy', 'Wang, Jianwei', 'Hung, Tao']",PLoS One,,,True
aae1603af1bb84087248441716a5c0bd373603b7,PMC,H1N1pdm09 Adjuvanted Vaccination in HIV-Infected Adults: A Randomized Trial of Two Single versus Two Double Doses,http://dx.doi.org/10.1371/journal.pone.0039310,PMC3382468,22761759,CC BY,"BACKGROUND: Since human immunodeficiency virus (HIV)-infected individuals are at increased risk of severe disease from pandemic influenza A (H1N1pdm09), vaccination was recommended as a prevention strategy. The aim of the present study was to evaluate the safety, immunogenicity and persistence of the immune response after vaccination against pandemic influenza A (H1N1pdm09) with an adjuvanted vaccine in human immunodeficiency virus (HIV)-infected adults using two single and two double doses. METHODOLOGY/PRINCIPAL FINDINGS: Open label, randomized trial to evaluate the immune response following H1N1pdm09 vaccination in HIV-infected participants compared to HIV-negative controls (NCT01155037). HIV-infected participants were randomized to receive 2 single (3.75 µg hemagglutinin) or 2 double (7.5 µg hemagglutinin) doses of the vaccine, 21 days apart. Controls received one dose of the vaccine. The primary endpoint was seroconversion as measured by hemagglutination inhibition assay. Two hundred fifty six HIV-infected participants (129 and 127 randomized to single and double doses, respectively) and 71 HIV-negative controls were enrolled. Among HIV-infected participants, seroconversion increased from 46.7% and 51.7% after the first dose to 77.2% and 83.8% after the second dose of the vaccine using single and double doses, respectively. Participants aged >40 years showed higher seroconversion compared to younger participants. Seroconversion among HIV-infected women and those with nadir CD4<200 cells/mm(3) was significantly higher with double doses. Persistence of protective antibodies six months after vaccination was achieved by 80% and 89.9% of the HIV-infected participants who received single and double doses, respectively. CONCLUSIONS/SIGNIFICANCE: Our results support the recommendation of two double doses of adjuvanted H1N1pdm09 vaccine for HIV-infected individuals, particularly women, and those aged >40 years or with nadir CD4<200 cells/mm(3), to achieve antibody levels that are both higher and more sustained. TRIAL REGISTRATION: ClinicalTrials.gov NCT01155037",2012 Jun 25,"['Santini-Oliveira, Marilia', 'Camacho, Luiz A. B.', 'Souza, Thiago M. L.', 'Luz, Paula M.', 'Vasconcellos, Mauricio T. L.', 'Giacoia-Gripp, Carmem B. W.', 'Morgado, Mariza G.', 'Nunes, Estevão P.', 'Lemos, Alberto S.', 'Ferreira, Ana C. G.', 'Moreira, Ronaldo I.', 'Veloso, Valdiléa G.', 'Siqueira, Marilda M.', 'Grinsztejn, Beatriz']",PLoS One,,,True
af400a711649c6703b915e8a935dfe778bc42132,PMC,H1N1pdm09 Adjuvanted Vaccination in HIV-Infected Adults: A Randomized Trial of Two Single versus Two Double Doses,http://dx.doi.org/10.1371/journal.pone.0039310,PMC3382468,22761759,CC BY,"BACKGROUND: Since human immunodeficiency virus (HIV)-infected individuals are at increased risk of severe disease from pandemic influenza A (H1N1pdm09), vaccination was recommended as a prevention strategy. The aim of the present study was to evaluate the safety, immunogenicity and persistence of the immune response after vaccination against pandemic influenza A (H1N1pdm09) with an adjuvanted vaccine in human immunodeficiency virus (HIV)-infected adults using two single and two double doses. METHODOLOGY/PRINCIPAL FINDINGS: Open label, randomized trial to evaluate the immune response following H1N1pdm09 vaccination in HIV-infected participants compared to HIV-negative controls (NCT01155037). HIV-infected participants were randomized to receive 2 single (3.75 µg hemagglutinin) or 2 double (7.5 µg hemagglutinin) doses of the vaccine, 21 days apart. Controls received one dose of the vaccine. The primary endpoint was seroconversion as measured by hemagglutination inhibition assay. Two hundred fifty six HIV-infected participants (129 and 127 randomized to single and double doses, respectively) and 71 HIV-negative controls were enrolled. Among HIV-infected participants, seroconversion increased from 46.7% and 51.7% after the first dose to 77.2% and 83.8% after the second dose of the vaccine using single and double doses, respectively. Participants aged >40 years showed higher seroconversion compared to younger participants. Seroconversion among HIV-infected women and those with nadir CD4<200 cells/mm(3) was significantly higher with double doses. Persistence of protective antibodies six months after vaccination was achieved by 80% and 89.9% of the HIV-infected participants who received single and double doses, respectively. CONCLUSIONS/SIGNIFICANCE: Our results support the recommendation of two double doses of adjuvanted H1N1pdm09 vaccine for HIV-infected individuals, particularly women, and those aged >40 years or with nadir CD4<200 cells/mm(3), to achieve antibody levels that are both higher and more sustained. TRIAL REGISTRATION: ClinicalTrials.gov NCT01155037",2012 Jun 25,"['Santini-Oliveira, Marilia', 'Camacho, Luiz A. B.', 'Souza, Thiago M. L.', 'Luz, Paula M.', 'Vasconcellos, Mauricio T. L.', 'Giacoia-Gripp, Carmem B. W.', 'Morgado, Mariza G.', 'Nunes, Estevão P.', 'Lemos, Alberto S.', 'Ferreira, Ana C. G.', 'Moreira, Ronaldo I.', 'Veloso, Valdiléa G.', 'Siqueira, Marilda M.', 'Grinsztejn, Beatriz']",PLoS One,,,True
0f48ba54e2976264796ac7496f9080b52568fb51,PMC,Respiratory viral pathogens associated with lower respiratory tract disease among young children in the highlands of Papua New Guinea,http://dx.doi.org/10.1016/j.jcv.2012.04.008,PMC3383990,22595309,CC BY,"BACKGROUND: Acute lower respiratory tract infections (ALRI) commonly result in fatal outcomes in the young children of Papua New Guinea (PNG). However, comprehensive studies of the viral aetiology of ALRI have not been conducted in PNG for almost 30 years. OBJECTIVES: To determine the viruses associated with ALRI among children living in the PNG highlands using sensitive molecular detection techniques. STUDY DESIGN: Pernasal swabs were collected routinely between 1 week and 18 months of age and also during episodes of ALRI, as part of a neonatal pneumococcal conjugate vaccine trial. A tandem multiplex real-time PCR assay was used to test for a comprehensive range of respiratory viruses in samples collected from 221 young children. Picornavirus typing was supported by DNA sequence analysis. RESULTS: Recognized pathogenic respiratory viruses were detected in 198/273 (73%) samples collected from children with no evidence of ALRI and 69/80 (86%) samples collected during ALRI episodes. Human rhinoviruses (HRV) species A, B and C were detected in 152 (56%) samples from non-ALRI children and 50 (63%) samples collected during ALRI episodes. Partial structural region sequences for two new species C rhinoviruses were added to the GenBank database. ALRI was associated with detection of adenovirus species B (p < 0.01) or C (p < 0.05), influenza A (p < 0.0001) or respiratory syncytial virus (p < 0.0001). Multiple viruses were detected more often during ALRI episodes (49%) than when children displayed no symptoms of ALRI (18%) (p < 0.0001). CONCLUSIONS: The burden of infection with respiratory viruses remains significant in young children living in the PNG highlands.",2012 Jul,"['Chidlow, Glenys R.', 'Laing, Ingrid A.', 'Harnett, Gerald B.', 'Greenhill, Andrew R.', 'Phuanukoonnon, Suparat', 'Siba, Peter M.', 'Pomat, William S.', 'Shellam, Geoffrey R.', 'Smith, David W.', 'Lehmann, Deborah']",J Clin Virol,,,False
5326626cf66eb61f7f001c6557c23058b57fb2e2,PMC,Clarithromycin Suppresses Human Respiratory Syncytial Virus Infection-Induced Streptococcus pneumoniae Adhesion and Cytokine Production in a Pulmonary Epithelial Cell Line,http://dx.doi.org/10.1155/2012/528568,PMC3384978,22761540,CC BY,"Human respiratory syncytial virus (RSV) sometimes causes acute and severe lower respiratory tract illness in infants and young children. RSV strongly upregulates proinflammatory cytokines and the platelet-activating factor (PAF) receptor, which is a receptor for Streptococcus pneumoniae, in the pulmonary epithelial cell line A549. Clarithromycin (CAM), which is an antimicrobial agent and is also known as an immunomodulator, significantly suppressed RSV-induced production of interleukin-6, interleukin-8, and regulated on activation, normal T-cell expressed and secreted (RANTES). CAM also suppressed RSV-induced PAF receptor expression and adhesion of fluorescein-labeled S. pneumoniae cells to A549 cells. The RSV-induced S. pneumoniae adhesion was thought to be mediated by the host cell's PAF receptor. CAM, which exhibits antimicrobial and immunomodulatory activities, was found in this study to suppress the RSV-induced adhesion of respiratory disease-causing bacteria, S. pneumoniae, to host cells. Thus, CAM might suppress immunological disorders and prevent secondary bacterial infections during RSV infection.",2012 Jun 12,"['Yokota, Shin-ichi', 'Okabayashi, Tamaki', 'Hirakawa, Satoshi', 'Tsutsumi, Hiroyuki', 'Himi, Tetsuo', 'Fujii, Nobuhiro']",Mediators Inflamm,,,True
72ddf8d0c71b8b1ece743904f2acd2c1a00984c4,PMC,Inferring pandemic growth rates from sequence data,http://dx.doi.org/10.1098/rsif.2011.0850,PMC3385754,22337627,CC BY,"Using sequence data to infer population dynamics is playing an increasing role in the analysis of outbreaks. The most common methods in use, based on coalescent inference, have been widely used but not extensively tested against simulated epidemics. Here, we use simulated data to test the ability of both parametric and non-parametric methods for inference of effective population size (coded in the popular BEAST package) to reconstruct epidemic dynamics. We consider a range of simulations centred on scenarios considered plausible for pandemic influenza, but our conclusions are generic for any exponentially growing epidemic. We highlight systematic biases in non-parametric effective population size estimation. The most prominent such bias leads to the false inference of slowing of epidemic spread in the recent past even when the real epidemic is growing exponentially. We suggest some sampling strategies that could reduce (but not eliminate) some of the biases. Parametric methods can correct for these biases if the infected population size is large. We also explore how some poor sampling strategies (e.g. that over-represent epidemiologically linked clusters of cases) could dramatically exacerbate bias in an uncontrolled manner. Finally, we present a simple diagnostic indicator, based on coalescent density and which can easily be applied to reconstructed phylogenies, that identifies time-periods for which effective population size estimates are less likely to be biased. We illustrate this with an application to the 2009 H1N1 pandemic.",2012 Aug 7,"['de Silva, Eric', 'Ferguson, Neil M.', 'Fraser, Christophe']",J R Soc Interface,,,True
47ee3efc99d4ed2a08a7c8e677adfd98425dade6,PMC,Regulatory T Cells in Arterivirus and Coronavirus Infections: Do They Protect Against Disease or Enhance it?,http://dx.doi.org/10.3390/v4050833,PMC3386620,22754651,CC BY,"Regulatory T cells (T(regs)) are a subset of T cells that are responsible for maintaining peripheral immune tolerance and homeostasis. The hallmark of T(regs) is the expression of the forkhead box P3 (FoxP3) transcription factor. Natural regulatory T cells (nT(regs)) are a distinct population of T cells that express CD4 and FoxP3. nTregs develop in the thymus and function in maintaining peripheral immune tolerance. Other CD4(+), CD4(-)CD8(-), and CD8(+)CD28(-) T cells can be induced to acquire regulatory function by antigenic stimulation, depending on the cytokine milieu. Inducible (or adaptive) T(regs) frequently express high levels of the interleukin 2 receptor (CD25). Atypical T(regs) express FoxP3 and CD4 but have no surface expression of CD25. Type 1 regulatory T cells (Tr1 cells) produce IL-10, while T helper 3 cells (Th3) produce TGF-β. The function of inducible T(regs) is presumably to maintain immune homeostasis, especially in the context of chronic inflammation or infection. Induction of T(regs) in coronaviral infections protects against the more severe forms of the disease attributable to the host response. However, arteriviruses have exploited these T cell subsets as a means to dampen the immune response allowing for viral persistence. T(reg) induction or activation in the pathogenesis of disease has been described in both porcine reproductive and respiratory syndrome virus, lactate dehydrogenase elevating virus, and mouse hepatitis virus. This review discusses the development and biology of regulatory T cells in the context of arteriviral and coronaviral infection.",2012 May 15,"['Cecere, Thomas E.', 'Todd, S. Michelle', 'LeRoith, Tanya']",Viruses,,,True
fd71de909bf3d6539246e78e650a76f6eb90b23b,PMC,Post-Transcriptional Control of Type I Interferon Induction by Porcine Reproductive and Respiratory Syndrome Virus in Its Natural Host Cells,http://dx.doi.org/10.3390/v4050725,PMC3386621,22754646,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) is not only a poor inducer of type I interferon but also inhibits the efficient induction of type I interferon by porcine transmissible gastroenteritis virus (TGEV) and synthetic dsRNA molecules, Poly I:C. However, the mechanistic basis by which PRRSV interferes with the induction of type I interferon in its natural host cells remains less well defined. The purposes of this review are to summarize the key findings in supporting the post-transcriptional control of type I interferon in its natural host cells and to propose the possible role of translational control in the regulation of type I interferon induction by PRRSV.",2012 May 2,"['Wang, Xiuqing', 'Christopher-Hennings, Jane']",Viruses,,,True
62f5729ba9ae176c206cafd0221804a80772ea37,PMC,Protective Role of Toll-like Receptor 3-Induced Type I Interferon in Murine Coronavirus Infection of Macrophages,http://dx.doi.org/10.3390/v4050901,PMC3386628,22754655,CC BY,"Toll-like Receptors (TLRs) sense viral infections and induce production of type I interferons (IFNs), other cytokines, and chemokines. Viral recognition by TLRs and other pattern recognition receptors (PRRs) has been proven to be cell-type specific. Triggering of TLRs with selected ligands can be beneficial against some viral infections. Macrophages are antigen-presenting cells that express TLRs and have a key role in the innate and adaptive immunity against viruses. Coronaviruses (CoVs) are single-stranded, positive-sense RNA viruses that cause acute and chronic infections and can productively infect macrophages. Investigation of the interplay between CoVs and PRRs is in its infancy. We assessed the effect of triggering TLR2, TLR3, TLR4, and TLR7 with selected ligands on the susceptibility of the J774A.1 macrophage cell line to infection with murine coronavirus (mouse hepatitis virus, [MHV]). Stimulation of TLR2, TLR4, or TLR7 did not affect MHV production. In contrast, pre-stimulation of TLR3 with polyinosinic-polycytidylic acid (poly I:C) hindered MHV infection through induction of IFN-β in macrophages. We demonstrate that activation of TLR3 with the synthetic ligand poly I:C mediates antiviral immunity that diminishes (MHV-A59) or suppresses (MHV-JHM, MHV-3) virus production in macrophages.",2012 May 24,"['Mazaleuskaya, Liudmila', 'Veltrop, Rogier', 'Ikpeze, Nneka', 'Martin-Garcia, Julio', 'Navas-Martin, Sonia']",Viruses,,,True
ea4880d01d03a59bb3de58e8ae226c5487e38e6c,PMC,Comprehensive Biothreat Cluster Identification by PCR/Electrospray-Ionization Mass Spectrometry,http://dx.doi.org/10.1371/journal.pone.0036528,PMC3387173,22768032,CC0,"Technology for comprehensive identification of biothreats in environmental and clinical specimens is needed to protect citizens in the case of a biological attack. This is a challenge because there are dozens of bacterial and viral species that might be used in a biological attack and many have closely related near-neighbor organisms that are harmless. The biothreat agent, along with its near neighbors, can be thought of as a biothreat cluster or a biocluster for short. The ability to comprehensively detect the important biothreat clusters with resolution sufficient to distinguish the near neighbors with an extremely low false positive rate is required. A technological solution to this problem can be achieved by coupling biothreat group-specific PCR with electrospray ionization mass spectrometry (PCR/ESI-MS). The biothreat assay described here detects ten bacterial and four viral biothreat clusters on the NIAID priority pathogen and HHS/USDA select agent lists. Detection of each of the biothreat clusters was validated by analysis of a broad collection of biothreat organisms and near neighbors prepared by spiking biothreat nucleic acids into nucleic acids extracted from filtered environmental air. Analytical experiments were carried out to determine breadth of coverage, limits of detection, linearity, sensitivity, and specificity. Further, the assay breadth was demonstrated by testing a diverse collection of organisms from each biothreat cluster. The biothreat assay as configured was able to detect all the target organism clusters and did not misidentify any of the near-neighbor organisms as threats. Coupling biothreat cluster-specific PCR to electrospray ionization mass spectrometry simultaneously provides the breadth of coverage, discrimination of near neighbors, and an extremely low false positive rate due to the requirement that an amplicon with a precise base composition of a biothreat agent be detected by mass spectrometry.",2012 Jun 29,"['Sampath, Rangarajan', 'Mulholland, Niveen', 'Blyn, Lawrence B.', 'Massire, Christian', 'Whitehouse, Chris A.', 'Waybright, Nicole', 'Harter, Courtney', 'Bogan, Joseph', 'Miranda, Mary Sue', 'Smith, David', 'Baldwin, Carson', 'Wolcott, Mark', 'Norwood, David', 'Kreft, Rachael', 'Frinder, Mark', 'Lovari, Robert', 'Yasuda, Irene', 'Matthews, Heather', 'Toleno, Donna', 'Housley, Roberta', 'Duncan, David', 'Li, Feng', 'Warren, Robin', 'Eshoo, Mark W.', 'Hall, Thomas A.', 'Hofstadler, Steven A.', 'Ecker, David J.']",PLoS One,,,True
28bec3efe92c8567992ee35baecf2dc42bbc34ae,PMC,Comparative analysis of mycobacterium and related actinomycetes yields insight into the evolution of mycobacterium tuberculosis pathogenesis,http://dx.doi.org/10.1186/1471-2164-13-120,PMC3388012,22452820,CC BY,"BACKGROUND: The sequence of the pathogen Mycobacterium tuberculosis (Mtb) strain H37Rv has been available for over a decade, but the biology of the pathogen remains poorly understood. Genome sequences from other Mtb strains and closely related bacteria present an opportunity to apply the power of comparative genomics to understand the evolution of Mtb pathogenesis. We conducted a comparative analysis using 31 genomes from the Tuberculosis Database (TBDB.org), including 8 strains of Mtb and M. bovis, 11 additional Mycobacteria, 4 Corynebacteria, 2 Streptomyces, Rhodococcus jostii RHA1, Nocardia farcinia, Acidothermus cellulolyticus, Rhodobacter sphaeroides, Propionibacterium acnes, and Bifidobacterium longum. RESULTS: Our results highlight the functional importance of lipid metabolism and its regulation, and reveal variation between the evolutionary profiles of genes implicated in saturated and unsaturated fatty acid metabolism. It also suggests that DNA repair and molybdopterin cofactors are important in pathogenic Mycobacteria. By analyzing sequence conservation and gene expression data, we identify nearly 400 conserved noncoding regions. These include 37 predicted promoter regulatory motifs, of which 14 correspond to previously validated motifs, as well as 50 potential noncoding RNAs, of which we experimentally confirm the expression of four. CONCLUSIONS: Our analysis of protein evolution highlights gene families that are associated with the adaptation of environmental Mycobacteria to obligate pathogenesis. These families include fatty acid metabolism, DNA repair, and molybdopterin biosynthesis. Our analysis reinforces recent findings suggesting that small noncoding RNAs are more common in Mycobacteria than previously expected. Our data provide a foundation for understanding the genome and biology of Mtb in a comparative context, and are available online and through TBDB.org.",2012 Mar 28,"['McGuire, Abigail Manson', 'Weiner, Brian', 'Park, Sang Tae', 'Wapinski, Ilan', 'Raman, Sahadevan', 'Dolganov, Gregory', 'Peterson, Matthew', 'Riley, Robert', 'Zucker, Jeremy', 'Abeel, Thomas', 'White, Jared', 'Sisk, Peter', 'Stolte, Christian', 'Koehrsen, Mike', 'Yamamoto, Robert T', 'Iacobelli-Martinez, Milena', 'Kidd, Matthew J', 'Maer, Andreia M', 'Schoolnik, Gary K', 'Regev, Aviv', 'Galagan, James']",BMC Genomics,,,True
b3b492aee17ce67199d458de9b98bc219c2cbf3c,PMC,Estrogen Mediates Innate and Adaptive Immune Alterations to Influenza Infection in Pregnant Mice,http://dx.doi.org/10.1371/journal.pone.0040502,PMC3390370,22792357,CC BY,"Pregnancy is a leading risk factor for severe complications during an influenza virus infection. Women infected during their second and third trimesters are at increased risk for severe cardiopulmonary complications, premature delivery, and death. Here, we establish a murine model of aerosolized influenza infection during pregnancy. We find significantly altered innate antiviral responses in pregnant mice, including decreased levels of IFN-β, IL-1α, and IFN-γ at early time points of infection. We also find reduced cytotoxic T cell activity and delayed viral clearance. We further demonstrate that pregnancy levels of the estrogen 17-β-estradiol are able to induce key anti-inflammatory phenotypes in immune responses to the virus independently of other hormones or pregnancy-related stressors. We conclude that elevated estrogen levels result in an attenuated anti-viral immune response, and that pregnancy-associated morbidities occur in the context of this anti-inflammatory phenotype.",2012 Jul 5,"['Pazos, Michael A.', 'Kraus, Thomas A.', 'Muñoz-Fontela, César', 'Moran, Thomas M.']",PLoS One,,,True
5ae7223cc6ab3437ba262bb2bb47768948e01d59,PMC,Proteasome-Dependent Disruption of the E3 Ubiquitin Ligase Anaphase-Promoting Complex by HCMV Protein pUL21a,http://dx.doi.org/10.1371/journal.ppat.1002789,PMC3390409,22792066,CC BY,"The anaphase-promoting complex (APC) is an E3 ubiquitin ligase which controls ubiquitination and degradation of multiple cell cycle regulatory proteins. During infection, human cytomegalovirus (HCMV), a widespread pathogen, not only phosphorylates the APC coactivator Cdh1 via the multifunctional viral kinase pUL97, it also promotes degradation of APC subunits via an unknown mechanism. Using a proteomics approach, we found that a recently identified HCMV protein, pUL21a, interacted with the APC. Importantly, we determined that expression of pUL21a was necessary and sufficient for proteasome-dependent degradation of APC subunits APC4 and APC5. This resulted in APC disruption and required pUL21a binding to the APC. We have identified the proline-arginine amino acid pair at residues 109–110 in pUL21a to be critical for its ability to bind and regulate the APC. A point mutant virus in which proline-arginine were mutated to alanines (PR-AA) grew at wild-type levels. However, a double mutant virus in which the viral ability to regulate the APC was abrogated by both PR-AA point mutation and UL97 deletion was markedly more attenuated compared to the UL97 deletion virus alone. This suggests that these mutations are synthetically lethal, and that HCMV exploits two viral factors to ensure successful disruption of the APC to overcome its restriction on virus infection. This study reveals the HCMV protein pUL21a as a novel APC regulator and uncovers a unique viral mechanism to subvert APC activity.",2012 Jul 5,"['Fehr, Anthony R.', 'Gualberto, Nathaniel C.', 'Savaryn, John Paul', 'Terhune, Scott S.', 'Yu, Dong']",PLoS Pathog,,,True
f6b79474869aa89ef3a3cab01f39abac279c5132,PMC,Proteomic Profiling of the TRAF3 Interactome Network Reveals a New Role for the ER-to-Golgi Transport Compartments in Innate Immunity,http://dx.doi.org/10.1371/journal.ppat.1002747,PMC3390413,22792062,CC BY,"Tumor Necrosis Factor receptor-associated factor-3 (TRAF3) is a central mediator important for inducing type I interferon (IFN) production in response to intracellular double-stranded RNA (dsRNA). Here, we report the identification of Sec16A and p115, two proteins of the ER-to-Golgi vesicular transport system, as novel components of the TRAF3 interactome network. Notably, in non-infected cells, TRAF3 was found associated with markers of the ER-Exit-Sites (ERES), ER-to-Golgi intermediate compartment (ERGIC) and the cis-Golgi apparatus. Upon dsRNA and dsDNA sensing however, the Golgi apparatus fragmented into cytoplasmic punctated structures containing TRAF3 allowing its colocalization and interaction with Mitochondrial AntiViral Signaling (MAVS), the essential mitochondria-bound RIG-I-like Helicase (RLH) adaptor. In contrast, retention of TRAF3 at the ER-to-Golgi vesicular transport system blunted the ability of TRAF3 to interact with MAVS upon viral infection and consequently decreased type I IFN response. Moreover, depletion of Sec16A and p115 led to a drastic disorganization of the Golgi paralleled by the relocalization of TRAF3, which under these conditions was unable to associate with MAVS. Consequently, upon dsRNA and dsDNA sensing, ablation of Sec16A and p115 was found to inhibit IRF3 activation and anti-viral gene expression. Reciprocally, mild overexpression of Sec16A or p115 in Hec1B cells increased the activation of IFNβ, ISG56 and NF-κB -dependent promoters following viral infection and ectopic expression of MAVS and Tank-binding kinase-1 (TBK1). In line with these results, TRAF3 was found enriched in immunocomplexes composed of p115, Sec16A and TBK1 upon infection. Hence, we propose a model where dsDNA and dsRNA sensing induces the formation of membrane-bound compartments originating from the Golgi, which mediate the dynamic association of TRAF3 with MAVS leading to an optimal induction of innate immune responses.",2012 Jul 5,"['van Zuylen, Wendy J.', 'Doyon, Priscilla', 'Clément, Jean-François', 'Khan, Kashif Aziz', ""D'Ambrosio, Lisa M."", 'Dô, Florence', 'St-Amant-Verret, Myriam', 'Wissanji, Tasheen', 'Emery, Gregory', 'Gingras, Anne-Claude', 'Meloche, Sylvain', 'Servant, Marc J.']",PLoS Pathog,,,True
db01b3a1badd793717ba425dc52f976f0212e763,PMC,"The Four Horsemen of the Apocalypse: Tropical Medicine in the Fight against Plague, Death, Famine, and War",http://dx.doi.org/10.4269/ajtmh.2012.11-0814,PMC3391054,22764283,CC BY,,2012 Jul 1,"Hotez, Peter J.",Am J Trop Med Hyg,,,True
778543806bc7ebe5596c085cf9a0421d0c0a1a2f,PMC,Localization and Sub-Cellular Shuttling of HTLV-1 Tax with the miRNA Machinery,http://dx.doi.org/10.1371/journal.pone.0040662,PMC3393700,22808228,CC BY,"The innate ability of the human cell to silence endogenous retroviruses through RNA sequences encoding microRNAs, suggests that the cellular RNAi machinery is a major means by which the host mounts a defense response against present day retroviruses. Indeed, cellular miRNAs target and hybridize to specific sequences of both HTLV-1 and HIV-1 viral transcripts. However, much like the variety of host immune responses to retroviral infection, the virus itself contains mechanisms that assist in the evasion of viral inhibition through control of the cellular RNAi pathway. Retroviruses can hijack both the enzymatic and catalytic components of the RNAi pathway, in some cases to produce novel viral miRNAs that can either assist in active viral infection or promote a latent state. Here, we show that HTLV-1 Tax contributes to the dysregulation of the RNAi pathway by altering the expression of key components of this pathway. A survey of uninfected and HTLV-1 infected cells revealed that Drosha protein is present at lower levels in all HTLV-1 infected cell lines and in infected primary cells, while other components such as DGCR8 were not dramatically altered. We show colocalization of Tax and Drosha in the nucleus in vitro as well as coimmunoprecipitation in the presence of proteasome inhibitors, indicating that Tax interacts with Drosha and may target it to specific areas of the cell, namely, the proteasome. In the presence of Tax we observed a prevention of primary miRNA cleavage by Drosha. Finally, the changes in cellular miRNA expression in HTLV-1 infected cells can be mimicked by the add back of Drosha or the addition of antagomiRs against the cellular miRNAs which are downregulated by the virus.",2012 Jul 10,"['Van Duyne, Rachel', 'Guendel, Irene', 'Klase, Zachary', 'Narayanan, Aarthi', 'Coley, William', 'Jaworski, Elizabeth', 'Roman, Jessica', 'Popratiloff, Anastas', 'Mahieux, Renaud', 'Kehn-Hall, Kylene', 'Kashanchi, Fatah']",PLoS One,,,True
d5878fe0a378d553186b212eeaadaa60257e933f,PMC,"Naturally-Occurring Genetic Variants in Human DC-SIGN Increase HIV-1 Capture, Cell-Transfer and Risk of Mother-To-Child Transmission",http://dx.doi.org/10.1371/journal.pone.0040706,PMC3393705,22808239,CC BY,"BACKGROUND: Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Dendritic cell–specific ICAM-3 grabbing-nonintegrin (DC-SIGN, also known as CD209) is an HIV-1 receptor that enhances its transmission to T cells and is expressed on placental macrophages. METHODS AND FINDINGS: We have investigated the association between DC-SIGN genetic variants and risk of MTCT of HIV-1 among Zimbabwean infants and characterized the impact of the associated mutations on DC-SIGN expression and interaction with HIV-1. DC-SIGN promoter (p-336C and p-201A) and exon 4 (198Q and 242V) variants were all significantly associated with increased risk of intrauterine (IU) HIV-1 infection. Promoter variants decreased DC-SIGN expression both in vitro and in placental CD163(+) macrophages (Hofbauer cells) of HIV-1 unexposed infants but not of HIV-1 exposed infants. The exon 4 protein-modifying mutations increased HIV-1 capture and transmission to T cells in vitro. CONCLUSION: This study provides compelling evidence to support an important role of DC-SIGN in IU HIV-1 infection.",2012 Jul 10,"['Boily-Larouche, Geneviève', 'Milev, Miroslav P.', 'Zijenah, Lynn S.', 'Labbé, Annie-Claude', 'Zannou, Djimon M.', 'Humphrey, Jean H.', 'Ward, Brian J.', 'Poudrier, Johanne', 'Mouland, Andrew J.', 'Cohen, Éric A.', 'Roger, Michel']",PLoS One,,,True
3c787e585321cc1d3d62aacb1c74713a4c77e9cc,PMC,A New Model for Hendra Virus Encephalitis in the Mouse,http://dx.doi.org/10.1371/journal.pone.0040308,PMC3393746,22808132,CC BY,"Hendra virus (HeV) infection in humans is characterized by an influenza like illness, which may progress to pneumonia or encephalitis and lead to death. The pathogenesis of HeV infection is poorly understood, and the lack of a mouse model has limited the opportunities for pathogenetic research. In this project we reassessed the role of mice as an animal model for HeV infection and found that mice are susceptible to HeV infection after intranasal exposure, with aged mice reliably developing encephalitic disease. We propose an anterograde route of neuroinvasion to the brain, possibly along olfactory nerves. This is supported by evidence for the development of encephalitis in the absence of viremia and the sequential distribution of viral antigen along pathways of olfaction in the brain of intranasally challenged animals. In our studies mice developed transient lower respiratory tract infection without progressing to viremia and systemic vasculitis that is common to other animal models. These studies report a new animal model of HeV encephalitis that will allow more detailed studies of the neuropathogenesis of HeV infection, particularly the mode of viral spread and possible sequestration within the central nervous system; investigation of mechanisms that moderate the development of viremia and systemic disease; and inform the development of improved treatment options for human patients.",2012 Jul 10,"['Dups, Johanna', 'Middleton, Deborah', 'Yamada, Manabu', 'Monaghan, Paul', 'Long, Fenella', 'Robinson, Rachel', 'Marsh, Glenn A.', 'Wang, Lin-Fa']",PLoS One,,,True
6fc6b211d30d357b07a3d6de138a6964363ef154,PMC,Retroviral Env Glycoprotein Trafficking and Incorporation into Virions,http://dx.doi.org/10.1155/2012/682850,PMC3395148,22811910,CC BY,"Together with the Gag protein, the Env glycoprotein is a major retroviral structural protein and is essential for forming infectious virus particles. Env is synthesized, processed, and transported to certain microdomains at the plasma membrane and takes advantage of the same host machinery for its trafficking as that used by cellular glycoproteins. Incorporation of Env into progeny virions is probably mediated by the interaction between Env and Gag, in some cases with the additional involvement of certain host factors. Although several general models have been proposed to explain the incorporation of retroviral Env glycoproteins into virions, the actual mechanism for this process is still unclear, partly because structural data on the Env protein cytoplasmic tail is lacking. This paper presents the current understanding of the synthesis, trafficking, and virion incorporation of retroviral Env proteins.",2012 Jul 2,"Murakami, Tsutomu",Mol Biol Int,,,True
58f93bf42d2c4e21ed8effe492719d992849eff6,PMC,"Production, Characterization and Applications for Toxoplasma gondii-Specific Polyclonal Chicken Egg Yolk Immunoglobulins",http://dx.doi.org/10.1371/journal.pone.0040391,PMC3395712,22808150,CC BY,"BACKGROUND: Toxoplasma gondii may cause abortions, ocular and neurological disorders in warm-blood hosts. Immunized mammals are a wide source of hyperimmune sera used in different approaches, including diagnosis and the study of host-parasite interactions. Unfortunately, mammalian antibodies present limitations for its production, such as the necessity for animal bleeding, low yield, interference with rheumatoid factor, complement activation and affinity to Fc mammalian receptors. IgY antibodies avoid those limitations; therefore they could be an alternative to be applied in T. gondii model. METHODOLOGY/PRINCIPAL FINDINGS: In this study we immunized hens with soluble tachyzoite antigens of T. gondii (STAg) and purified egg yolk antibodies (IgY) by an inexpensive and simple method, with high yield and purity degree. IgY anti-STAg antibodies presented high avidity and were able to recognize a broad range of parasite antigens, although some marked differences were observed in reactivity profile between antibodies produced in immunized hens and mice. Interestingly, IgY antibodies against Neospora caninum and Eimeria spp. did not react to STAg. We also show that IgY antibodies were suitable to detect T. gondii forms in paraffin-embedded sections and culture cell monolayers. CONCLUSIONS/SIGNIFICANCE: Due to its cost-effectiveness, high production yield and varied range of possible applications, polyclonal IgY antibodies are useful tools for studies involving T. gondii.",2012 Jul 12,"['Ferreira Júnior, Álvaro', 'Santiago, Fernanda M.', 'Silva, Murilo V.', 'Ferreira, Flávia B.', 'Macêdo Júnior, Arlindo G.', 'Mota, Caroline M.', 'Faria, Matheus S.', 'Filho, Hercílio H. Silva', 'Silva, Deise A. O.', 'Cunha-Júnior, Jair P.', 'Mineo, José R.', 'Mineo, Tiago W. P.']",PLoS One,,,True
f5e974ef3a8c983ae63ac4f4aa2b6ec0e3678032,PMC,Recent Progress in Studies of Arterivirus- and Coronavirus-Host Interactions,http://dx.doi.org/10.3390/v4060980,PMC3397358,22816036,CC BY,"Animal coronaviruses, such as infectious bronchitis virus (IBV), and arteriviruses, such as porcine reproductive and respiratory syndrome virus (PRRSV), are able to manifest highly contagious infections in their specific native hosts, thereby arising in critical economic damage to animal industries. This review discusses recent progress in studies of virus-host interactions during animal and human coronavirus and arterivirus infections, with emphasis on IBV-host cell interactions. These interactions may be directly involved in viral replication or lead to the alteration of certain signaling pathways, such as cell stress response and innate immunity, to facilitate viral replication and pathogenesis.",2012 Jun 19,"['Zhong, Yanxin', 'Tan, Yong Wah', 'Liu, Ding Xiang']",Viruses,,,True
55ef87ca0d0cdad3973a94294211e8e9ea8bcc87,PMC,Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein,http://dx.doi.org/10.3390/v4061011,PMC3397359,22816037,CC BY,"Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm. To deliver their nucleocapsid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus entry and is a primary determinant of cell tropism and pathogenesis. It is classified as a class I fusion protein, and is responsible for binding to the receptor on the host cell as well as mediating the fusion of host and viral membranes—A process driven by major conformational changes of the S protein. This review discusses coronavirus entry mechanisms focusing on the different triggers used by coronaviruses to initiate the conformational change of the S protein: receptor binding, low pH exposure and proteolytic activation. We also highlight commonalities between coronavirus S proteins and other class I viral fusion proteins, as well as distinctive features that confer distinct tropism, pathogenicity and host interspecies transmission characteristics to coronaviruses.",2012 Jun 20,"['Belouzard, Sandrine', 'Millet, Jean K.', 'Licitra, Beth N.', 'Whittaker, Gary R.']",Viruses,,,True
08dd1169c7aa45621e5f48bf6246b049e071e445,PMC,Evaluation of Four Different Systems for Extraction of RNA from Stool Suspensions Using MS-2 Coliphage as an Exogenous Control for RT-PCR Inhibition,http://dx.doi.org/10.1371/journal.pone.0039455,PMC3397973,22815706,CC BY,"Knowing when, and to what extent co-extracted inhibitors interfere with molecular RNA diagnostic assays is of utmost importance. The QIAamp Viral RNA Mini Kit (A); MagNA Pure LC2.0 Automatic extractor (B); KingFisher (C); and NucliSENS EasyMag (D) RNA extraction systems were evaluated for extraction efficiency and co-purification of inhibitors from stool suspensions. Real-Time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) of MS-2 coliphage spiked into each system’s lysis buffer served as an external control for both. Cycle thresholds (Cts) of the MS2 were determined for RNA extracted from stool suspensions containing unknown (n = 93) or varying amounts of inhibitors (n = 92). Stool suspensions from the latter group were also used to determine whether MS-2 and enterovirus rRT-PCR inhibitions were correlated. Specifically 23 RNA extracts from stool suspensions were spiked with enterovirus RNA after extraction and 13 of these stool suspension were spiked with intact enterovirus before extraction. MS2 rRT-PCR inhibition varied for RNAs extracted by the different systems. Inhibition was noted in 12 (13.0%), 26 (28.3%), 7 (7.6%), and 7 (7.6%) of the first 93 RNA extracts, and 58 (63.0%), 55 (59.8%), 37 (40.2%) and 30 (32.6%) of the second 92 extracts for A, B, C, and D, respectively. Furthermore, enterovirus rRT-PCR inhibition correlated with MS2 rRT-PCR inhibition for added enterovirus RNA or virus particles. In conclusion, rRT-PCR for MS-2 RNA is a good predictor of inhibition of enterovirus RNA extracted from stool suspensions. EasyMag performed the best, however all four extraction methods were suitable provided that external controls identified problematic samples.",2012 Jul 16,"['Shulman, Lester M.', 'Hindiyeh, Musa', 'Muhsen, Khitam', 'Cohen, Dani', 'Mendelson, Ella', 'Sofer, Danit']",PLoS One,,,True
1997909a084ca1b2b76a4f13bdcc9a320058db13,PMC,Evaluation of Four Different Systems for Extraction of RNA from Stool Suspensions Using MS-2 Coliphage as an Exogenous Control for RT-PCR Inhibition,http://dx.doi.org/10.1371/journal.pone.0039455,PMC3397973,22815706,CC BY,"Knowing when, and to what extent co-extracted inhibitors interfere with molecular RNA diagnostic assays is of utmost importance. The QIAamp Viral RNA Mini Kit (A); MagNA Pure LC2.0 Automatic extractor (B); KingFisher (C); and NucliSENS EasyMag (D) RNA extraction systems were evaluated for extraction efficiency and co-purification of inhibitors from stool suspensions. Real-Time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) of MS-2 coliphage spiked into each system’s lysis buffer served as an external control for both. Cycle thresholds (Cts) of the MS2 were determined for RNA extracted from stool suspensions containing unknown (n = 93) or varying amounts of inhibitors (n = 92). Stool suspensions from the latter group were also used to determine whether MS-2 and enterovirus rRT-PCR inhibitions were correlated. Specifically 23 RNA extracts from stool suspensions were spiked with enterovirus RNA after extraction and 13 of these stool suspension were spiked with intact enterovirus before extraction. MS2 rRT-PCR inhibition varied for RNAs extracted by the different systems. Inhibition was noted in 12 (13.0%), 26 (28.3%), 7 (7.6%), and 7 (7.6%) of the first 93 RNA extracts, and 58 (63.0%), 55 (59.8%), 37 (40.2%) and 30 (32.6%) of the second 92 extracts for A, B, C, and D, respectively. Furthermore, enterovirus rRT-PCR inhibition correlated with MS2 rRT-PCR inhibition for added enterovirus RNA or virus particles. In conclusion, rRT-PCR for MS-2 RNA is a good predictor of inhibition of enterovirus RNA extracted from stool suspensions. EasyMag performed the best, however all four extraction methods were suitable provided that external controls identified problematic samples.",2012 Jul 16,"['Shulman, Lester M.', 'Hindiyeh, Musa', 'Muhsen, Khitam', 'Cohen, Dani', 'Mendelson, Ella', 'Sofer, Danit']",PLoS One,,,False
35b637a1564ebf2f7d89ba7196a2cee30bdc9b0c,PMC,Evaluation of Four Different Systems for Extraction of RNA from Stool Suspensions Using MS-2 Coliphage as an Exogenous Control for RT-PCR Inhibition,http://dx.doi.org/10.1371/journal.pone.0039455,PMC3397973,22815706,CC BY,"Knowing when, and to what extent co-extracted inhibitors interfere with molecular RNA diagnostic assays is of utmost importance. The QIAamp Viral RNA Mini Kit (A); MagNA Pure LC2.0 Automatic extractor (B); KingFisher (C); and NucliSENS EasyMag (D) RNA extraction systems were evaluated for extraction efficiency and co-purification of inhibitors from stool suspensions. Real-Time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) of MS-2 coliphage spiked into each system’s lysis buffer served as an external control for both. Cycle thresholds (Cts) of the MS2 were determined for RNA extracted from stool suspensions containing unknown (n = 93) or varying amounts of inhibitors (n = 92). Stool suspensions from the latter group were also used to determine whether MS-2 and enterovirus rRT-PCR inhibitions were correlated. Specifically 23 RNA extracts from stool suspensions were spiked with enterovirus RNA after extraction and 13 of these stool suspension were spiked with intact enterovirus before extraction. MS2 rRT-PCR inhibition varied for RNAs extracted by the different systems. Inhibition was noted in 12 (13.0%), 26 (28.3%), 7 (7.6%), and 7 (7.6%) of the first 93 RNA extracts, and 58 (63.0%), 55 (59.8%), 37 (40.2%) and 30 (32.6%) of the second 92 extracts for A, B, C, and D, respectively. Furthermore, enterovirus rRT-PCR inhibition correlated with MS2 rRT-PCR inhibition for added enterovirus RNA or virus particles. In conclusion, rRT-PCR for MS-2 RNA is a good predictor of inhibition of enterovirus RNA extracted from stool suspensions. EasyMag performed the best, however all four extraction methods were suitable provided that external controls identified problematic samples.",2012 Jul 16,"['Shulman, Lester M.', 'Hindiyeh, Musa', 'Muhsen, Khitam', 'Cohen, Dani', 'Mendelson, Ella', 'Sofer, Danit']",PLoS One,,,False
e4722dbdd2d7a467fcfd82700a2493e5ee6efd9e,PMC,Reduction in Clostridium difficile Infection Rates after Mandatory Hospital Public Reporting: Findings from a Longitudinal Cohort Study in Canada,http://dx.doi.org/10.1371/journal.pmed.1001268,PMC3398960,22815656,CC BY,"BACKGROUND: The role of public reporting in improving hospital quality of care is controversial. Reporting of hospital-acquired infection rates has been introduced in multiple health care systems, but its relationship to infection rates has been understudied. Our objective was to determine whether mandatory public reporting by hospitals is associated with a reduction in hospital rates of Clostridium difficile infection. METHODS AND FINDINGS: We conducted a longitudinal, population-based cohort study in Ontario (Canada's largest province) between April 1, 2002, and March 31, 2010. We included all patients (>1 y old) admitted to 180 acute care hospitals. Using Poisson regression, we developed a model to predict hospital- and age-specific monthly rates of C. difficile disease per 10,000 patient-days prior to introduction of public reporting on September 1, 2008. We then compared observed monthly rates of C. difficile infection in the post-intervention period with rates predicted by the pre-intervention predictive model. In the pre-intervention period there were 33,634 cases of C. difficile infection during 39,221,113 hospital days, with rates increasing from 7.01 per 10,000 patient-days in 2002 to 10.79 in 2007. In the first calendar year after the introduction of public reporting, there was a decline in observed rates of C. difficile colitis in Ontario to 8.92 cases per 10,000 patient-days, which was significantly lower than the predicted rate of 12.16 (95% CI 11.35–13.04) cases per 10,000 patient-days (p<0.001). Over this period, public reporting was associated with a 26.7% (95% CI 21.4%–31.6%) reduction in C. difficile cases, or a projected 1,970 cases averted per year (95% CI 1,476–2,500). The effect was specific to C. difficile, with rates of community-acquired gastrointestinal infections and urinary tract infections unchanged. A limitation of our study is that this observational study design cannot rule out the influence of unmeasured temporal confounders. CONCLUSIONS: Public reporting of hospital C. difficile rates was associated with a substantial reduction in the population burden of this infection. Future research will be required to discern the direct mechanism by which C. difficile infection rates may have been reduced in response to public reporting. Please see later in the article for the Editors' Summary",2012 Jul 17,"['Daneman, Nick', 'Stukel, Therese A.', 'Ma, Xiaomu', 'Vermeulen, Marian', 'Guttmann, Astrid']",PLoS Med,,,True
c229a350536a9e087003fb14e9e52aab0245d2ec,PMC,Exploring IRES Region Accessibility by Interference of Foot-and-Mouth Disease Virus Infectivity,http://dx.doi.org/10.1371/journal.pone.0041382,PMC3399821,22815996,CC BY,"Translation initiation of picornavirus RNA is driven by an internal ribosome entry site (IRES) element located upstream of the initiator codon. RNA structure organization as well as RNA-protein interaction plays a fundamental role in internal initiation. IRES activity has been mainly analyzed in the context of reporter genes, lacking regions of the viral genome potentially affecting translation efficiency. With the aim to understand the vulnerability of the IRES and translation start region to small molecules in the context of the viral genome, we designed a set of customized RNase-resistant 2′O-methyl antisense oligoribonucleotides (2′OMe AONs) based on RNA structure data. These AONs were then used to monitor their capacity to interfere viral RNA translation, and thus, to inhibit virus yield. Foot-and-mouth disease virus (FMDV) RNA translation can be initiated at two in-frame AUG codons. We show here that a 2′OMe AON complementary to AUG2 inhibited viral multiplication more efficiently than the one that targeted AUG1. Furthermore, the response of the viral RNA to AONs targeting the IRES region denoted important differences between tissue culture cells and cell-free systems, reinforcing the need to analyze viral RNA response in living cells. Importantly, we have identified four specific motifs within the IRES element that are targets for viral inhibitors both in tissue culture cells and in cell-free systems. The identified targets define accessible regions to small molecules, which disturb either the RNA structural organization or the RNA-protein interactions needed to initiate translation in FMDV RNA.",2012 Jul 18,"['Fajardo, Teodoro', 'Rosas, Maria Flora', 'Sobrino, Francisco', 'Martinez-Salas, Encarnacion']",PLoS One,,,True
9d2c6b24e096eac147115b77f295e0ddcb5435c6,PMC,Molecular Imaging Reveals a Progressive Pulmonary Inflammation in Lower Airways in Ferrets Infected with 2009 H1N1 Pandemic Influenza Virus,http://dx.doi.org/10.1371/journal.pone.0040094,PMC3401186,22911695,CC BY,"Molecular imaging has gained attention as a possible approach for the study of the progression of inflammation and disease dynamics. Herein we used [(18)F]-2-deoxy-2-fluoro-D-glucose ([(18)F]-FDG) as a radiotracer for PET imaging coupled with CT (FDG-PET/CT) to gain insight into the spatiotemporal progression of the inflammatory response of ferrets infected with a clinical isolate of a pandemic influenza virus, H1N1 (H1N1pdm). The thoracic regions of mock- and H1N1pdm-infected ferrets were imaged prior to infection and at 1, 2, 3 and 6 days post-infection (DPI). On 1 DPI, FDG-PET/CT imaging revealed areas of consolidation in the right caudal lobe which corresponded with elevated [(18)F]-FDG uptake (maximum standardized uptake values (SUVMax), 4.7–7.0). By days 2 and 3, consolidation (CT) and inflammation ([(18)F]-FDG) appeared in the left caudal lobe. By 6 DPI, CT images showed extensive areas of patchy ground-glass opacities (GGO) and consolidations with the largest lesions having high SUVMax (6.0–7.6). Viral shedding and replication were detected in most nasal, throat and rectal swabs and nasal turbinates and lungs on 1, 2 and 3 DPI, but not on day 7, respectively. In conclusion, molecular imaging of infected ferrets revealed a progressive consolidation on CT with corresponding [(18)F]-FDG uptake. Strong positive correlations were measured between SUVMax and bronchiolitis-related pathologic scoring (Spearman’s ρ = 0.75). Importantly, the extensive areas of patchy GGO and consolidation seen on CT in the ferret model at 6 DPI are similar to that reported for human H1N1pdm infections. In summary, these first molecular imaging studies of lower respiratory infection with H1N1pdm show that FDG-PET can give insight into the spatiotemporal progression of the inflammation in real-time.",2012 Jul 20,"['Jonsson, Colleen B.', 'Camp, Jeremy V.', 'Wu, Albert', 'Zheng, Huaiyu', 'Kraenzle, Jennifer L.', 'Biller, Ashley E.', 'Vanover, Carol D.', 'Chu, Yong-Kyu', 'Ng, Chin K.', 'Proctor, Mary', 'Sherwood, Leslie', 'Steffen, Marlene C.', 'Mollura, Daniel J.']",PLoS One,,,True
3b1fca9311e0efc4368f3775dd878f57c5978a5e,PMC,The Effects of Simvastatin or Interferon-α on Infectivity of Human Norovirus Using a Gnotobiotic Pig Model for the Study of Antivirals,http://dx.doi.org/10.1371/journal.pone.0041619,PMC3402445,22911825,CC BY,"The lack of an animal model for human norovirus (HuNoV) has hindered the development of therapeutic strategies. This study demonstrated that a commonly used cholesterol-lowering statin medication, simvastatin, which increases HuNoV replication in an in vitro replicon system, also enhances HuNoV infectivity in the gnotobiotic (Gn) pig model. In contrast, oral treatment with interferon (IFN)-α reduces HuNoV infectivity. Young piglets, all with A or H1 histo-blood group antigens on enterocytes, were treated orally with 8 mg/kg/day of simvastatin; 5 days later, the pigs were inoculated orally with a GII.4 HuNoV (HS194/2009/US strain) and then treated with simvastatin for 5 more days. Simvastatin induced significantly earlier onset and longer duration of HuNoV fecal shedding in treated pigs, frequently with higher fecal viral titers. Simvastatin impaired poly (I:C)-induced IFN-α expression in macrophages or dendritic cells, possibly due to lowered toll-like receptor (TLR) 3 expression; however, the mechanisms were not related to interferon regulatory factor 3 or nuclear factor kappa B signaling pathway. Thus, the enhanced, earlier infectivity of HuNoV in simvastatin-treated pigs coincided with the inhibitory effect of simvastatin on innate immunity. In contrast to the increased HuNoV shedding that simvastatin induced, viral shedding during the treatment period was reduced or curtailed in the HuNoV-inoculated pigs pre-treated/treated with human IFN-α. Our findings are the first to indicate that IFN-α has potential as antiviral therapy against HuNoV. Based on these intriguing and novel findings using the Gn pig model, we confirmed that HuNoV infectivity is altered by treatment with simvastatin or IFN-α. Collectively, these findings indicate that Gn pigs are a useful model to test immunomodulators or efficacy of antivirals against HuNoV.",2012 Jul 23,"['Jung, Kwonil', 'Wang, Qiuhong', 'Kim, Yunjeong', 'Scheuer, Kelly', 'Zhang, Zhenwen', 'Shen, Quan', 'Chang, Kyeong-Ok', 'Saif, Linda J.']",PLoS One,,,True
033810c43899f8bbaea3ecb2b86c192c0e020451,PMC,"Acute respiratory infections, influenza-like illness and JIA: impact on disease activity and response to the influenza vaccine",http://dx.doi.org/10.1186/1546-0096-10-S1-A103,PMC3403110,,CC BY,,2012 Jul 13,"['Carvalho, Luciana M', 'Paula, Flávia E', 'Silvestre, Rodrigo VD', 'Roberti, Luciana R', 'Mello, Wyller A', 'Arruda, Eurico', 'Ferriani, Virginia PL']",Pediatr Rheumatol Online J,,,False
16283e25f01d47898ad2b82d56bd81d5ccf44a5d,PMC,Suppression of feline coronavirus replication in vitro by cyclosporin A,http://dx.doi.org/10.1186/1297-9716-43-41,PMC3403912,22546085,CC BY,"The feline infectious peritonitis virus (FIPV) is a member of the feline coronavirus family that causes FIP, which is incurable and fatal in cats. Cyclosporin A (CsA), an immunosuppressive agent that targets the nuclear factor pathway of activated T-cells (NF-AT) to bind cellular cyclophilins (CyP), dose-dependently inhibited FIPV replication in vitro. FK506 (an immunosuppressor of the pathway that binds cellular FK506-binding protein (FKBP) but not CyP) did not affect FIPV replication. Neither cell growth nor viability changed in the presence of either CsA or FK506, and these factors did not affect the NF-AT pathway in fcwf-4 cells. Therefore, CsA does not seem to exert inhibitory effects via the NF-AT pathway. In conclusion, CsA inhibited FIPV replication in vitro and further studies are needed to verify the practical value of CsA as an anti-FIPV treatment in vivo.",2012 Apr 30,"['Tanaka, Yoshikazu', 'Sato, Yuka', 'Osawa, Shuichi', 'Inoue, Mai', 'Tanaka, Satoka', 'Sasaki, Takashi']",Vet Res,,,True
49a40a6447a61f2a4a725095b19ac648419c09f7,PMC,"The Dynamics, Causes and Possible Prevention of Hepatitis E Outbreaks",http://dx.doi.org/10.1371/journal.pone.0041135,PMC3404073,22911752,CC BY,"Rapidly spreading infectious diseases are a serious risk to public health. The dynamics and the factors causing outbreaks of these diseases can be better understood using mathematical models, which are fit to data. Here we investigate the dynamics of a Hepatitis E outbreak in the Kitgum region of northern Uganda during 2007 to 2009. First, we use the data to determine that [Image: see text] is approximately 2.25 for the outbreak. Secondly, we use a model to estimate that the critical level of latrine and bore hole coverages needed to eradicate the epidemic is at least [Image: see text] and [Image: see text] respectively. Lastly, we further investigate the relationship between the co-infection factor for malaria and Hepatitis E on the value of [Image: see text] for Hepatitis E. Taken together, these results provide us with a better understanding of the dynamics and possible causes of Hepatitis E outbreaks.",2012 Jul 24,"['Nannyonga, Betty', 'Sumpter, David J. T.', 'Mugisha, Joseph Y. T.', 'Luboobi, Livingstone S.']",PLoS One,,,True
3fe4e2a98af36485a9a4dc93c30eef62522af0e0,PMC,Cytokine and Chemokine Levels in Patients with Severe Fever with Thrombocytopenia Syndrome Virus,http://dx.doi.org/10.1371/journal.pone.0041365,PMC3404083,22911786,CC BY,"BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV), which can cause hemorrhagic fever–like illness, is a newly discovered bunyavirus in China. The pathogenesis of SFTSV infection is poorly understood. However, it has been suggested that immune mechanisms, including cytokines and chemokines, play an important role in disease pathogenesis. In the present study, we investigated host cytokine and chemokine profiles in serum samples of patients with SFTSV infection from Northeast China and explored a possible correlation between cytokine levels and disease severity. METHODS AND PRINCIPAL FINDINGS: Acute phase serum samples from 40 patients, diagnosed with SFTSV infection were included. Patients were divided into two groups – severe or non-severe – based on disease severity. Levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, interleukin-6, interferon (IFN)-γ, IFN- γ-induced protein (IP)-10 and RANTES were measured in the serum samples with commercial ELISAs. Statistical analysis showed that increases in TNF-α, IP-10 and IFN-γ were associated with disease severity. CONCLUSIONS: We suggest that a cytokine-mediated inflammatory response, characterized by cytokine and chemokine production imbalance, might be in part responsible for the disease progression of patients with SFTSV infection.",2012 Jul 24,"['Deng, Baocheng', 'Zhang, Shujun', 'Geng, Yingzhi', 'Zhang, Yuzhong', 'Wang, Yuncheng', 'Yao, Wenqing', 'Wen, Ying', 'Cui, Wei', 'Zhou, Ying', 'Gu, Qiuhong', 'Wang, Wen', 'Wang, Yu', 'Shao, Zhen', 'Wang, Yanli', 'Li, Chengbo', 'Wang, Donglei', 'Zhao, Yitong', 'Liu, Pei']",PLoS One,,,True
3053729be9dadd6180b0b30ed2048dec12bd0401,PMC,Human Bocaviruses Are Not Significantly Associated with Gastroenteritis: Results of Retesting Archive DNA from a Case Control Study in the UK,http://dx.doi.org/10.1371/journal.pone.0041346,PMC3404102,22848470,CC BY,"Gastroenteritis is a common illness causing considerable morbidity and mortality worldwide. Despite improvements in detection methods, a significant diagnostic gap still remains. Human bocavirus (HBoV)s, which are associated with respiratory infections, have also frequently been detected in stool samples in cases of gastroenteritis, and a tentative association between HBoVs, and in particular type-2 HBoVs, and gastroenteritis has previously been made. The aim of this study was to determine the role of HBoVs in gastroenteritis, using archived DNA samples from the case-control Infectious Intestinal Disease Study (IID). DNA extracted from stool samples from 2,256 cases and 2,124 controls were tested for the presence of HBoV DNA. All samples were screened in a real time PCR pan-HBoV assay, and positive samples were then tested in genotype 1 to 3-specific assays. HBoV was detected in 7.4% but no significantly different prevalence was observed between cases and controls. In the genotype-specific assays 106 of the 324 HBoV-positive samples were genotyped, with HBoV-1 predominantly found in controls whilst HBoV-2 was more frequently associated with cases of gastroenteritis (p<0.01). A significant proportion of HBoV positives could not be typed using the type specific assays, 67% of the total positives, and this was most likely due to low viral loads being present in the samples. However, the distribution of the untyped HBoV strains was no different between cases and controls. In conclusion, HBoVs, including HBoV-2 do not appear to be a significant cause of gastroenteritis in the UK population.",2012 Jul 24,"['Nawaz, Sameena', 'Allen, David J.', 'Aladin, Farah', 'Gallimore, Christopher', 'Iturriza-Gómara, Miren']",PLoS One,,,True
dc45028785e8308de18df3a42fe11fe571da2cdc,PMC,Structural Origins for the Loss of Catalytic Activities of Bifunctional Human LTA4H Revealed through Molecular Dynamics Simulations,http://dx.doi.org/10.1371/journal.pone.0041063,PMC3405069,22848428,CC BY,"Human leukotriene A4 hydrolase (hLTA4H), which is the final and rate-limiting enzyme of arachidonic acid pathway, converts the unstable epoxide LTA4 to a proinflammatory lipid mediator LTB4 through its hydrolase function. The LTA4H is a bi-functional enzyme that also exhibits aminopeptidase activity with a preference over arginyl tripeptides. Various mutations including E271Q, R563A, and K565A have completely or partially abolished both the functions of this enzyme. The crystal structures with these mutations have not shown any structural changes to address the loss of functions. Molecular dynamics simulations of LTA4 and tripeptide complex structures with functional mutations were performed to investigate the structural and conformation changes that scripts the observed differences in catalytic functions. The observed protein-ligand hydrogen bonds and distances between the important catalytic components have correlated well with the experimental results. This study also confirms based on the structural observation that E271 is very important for both the functions as it holds the catalytic metal ion at its location for the catalysis and it also acts as N-terminal recognition residue during peptide binding. The comparison of binding modes of substrates revealed the structural changes explaining the importance of R563 and K565 residues and the required alignment of substrate at the active site. The results of this study provide valuable information to be utilized in designing potent hLTA4H inhibitors as anti-inflammatory agents.",2012 Jul 25,"['Thangapandian, Sundarapandian', 'John, Shalini', 'Lazar, Prettina', 'Choi, Sun', 'Lee, Keun Woo']",PLoS One,,,True
959c580ae16696d820337df5f221ea7869b71d69,PMC,Molecular and Microscopic Analysis of Bacteria and Viruses in Exhaled Breath Collected Using a Simple Impaction and Condensing Method,http://dx.doi.org/10.1371/journal.pone.0041137,PMC3405091,22848436,CC BY,"Exhaled breath condensate (EBC) is increasingly being used as a non-invasive method for disease diagnosis and environmental exposure assessment. By using hydrophobic surface, ice, and droplet scavenging, a simple impaction and condensing based collection method is reported here. Human subjects were recruited to exhale toward the device for 1, 2, 3, and 4 min. The exhaled breath quickly formed into tiny droplets on the hydrophobic surface, which were subsequently scavenged into a 10 µL rolling deionized water droplet. The collected EBC was further analyzed using culturing, DNA stain, Scanning Electron Microscope (SEM), polymerase chain reaction (PCR) and colorimetry (VITEK 2) for bacteria and viruses. Experimental data revealed that bacteria and viruses in EBC can be rapidly collected using the method developed here, with an observed efficiency of 100 µL EBC within 1 min. Culturing, DNA stain, SEM, and qPCR methods all detected high bacterial concentrations up to 7000 CFU/m(3) in exhaled breath, including both viable and dead cells of various types. Sphingomonas paucimobilis and Kocuria variants were found dominant in EBC samples using VITEK 2 system. SEM images revealed that most bacteria in exhaled breath are detected in the size range of 0.5–1.0 µm, which is able to enable them to remain airborne for a longer time, thus presenting a risk for airborne transmission of potential diseases. Using qPCR, influenza A H3N2 viruses were also detected in one EBC sample. Different from other devices restricted solely to condensation, the developed method can be easily achieved both by impaction and condensation in a laboratory and could impact current practice of EBC collection. Nonetheless, the reported work is a proof-of-concept demonstration, and its performance in non-invasive disease diagnosis such as bacterimia and virus infections needs to be further validated including effects of its influencing matrix.",2012 Jul 25,"['Xu, Zhenqiang', 'Shen, Fangxia', 'Li, Xiaoguang', 'Wu, Yan', 'Chen, Qi', 'Jie, Xu', 'Yao, Maosheng']",PLoS One,,,True
9aee0cad00998f83f85e815527be1a7ac00881ee,PMC,Antiviral Activity of Isatis indigotica Extract and Its Derived Indirubin against Japanese Encephalitis Virus,http://dx.doi.org/10.1155/2012/925830,PMC3405817,22911608,CC BY,"Isatis indigotica is widely used in Chinese Traditional Medicine for clinical treatment of virus infection, tumor, and inflammation, yet its antiviral activities remain unclear. This study probed antiviral activity of I. indigotica extract and its marker compounds against Japanese encephalitis virus (JEV). I. indigotica methanol extract, indigo, and indirubin proved less cytotoxic than other components, showing inhibitory effect (concentration-dependent) on JEV replication in vitro. Time-of-addition experiments proved the extract, indigo, and indirubin with potent antiviral effect by pretreatment (before infection) or simultaneous treatment (during infection), but not posttreatment (after entry). Antiviral action of these agents showed correlation with blocking virus attachment and exhibited potent virucidal activity. In particular, indirubin had strong protective ability in a mouse model with lethal JEV challenge. The study could yield anti-JEV agents.",2012 Jul 17,"['Chang, Shu-Jen', 'Chang, Yi-Chih', 'Lu, Kai-Zen', 'Tsou, Yi-Yun', 'Lin, Cheng-Wen']",Evid Based Complement Alternat Med,,,True
842df6edd1fa0ce2684a79447ad591b1093d83f3,PMC,IFN-γ Signaling to Astrocytes Protects from Autoimmune Mediated Neurological Disability,http://dx.doi.org/10.1371/journal.pone.0042088,PMC3407093,22848713,CC BY,"Demyelination and axonal degeneration are determinants of progressive neurological disability in patients with multiple sclerosis (MS). Cells resident within the central nervous system (CNS) are active participants in development, progression and subsequent control of autoimmune disease; however, their individual contributions are not well understood. Astrocytes, the most abundant CNS cell type, are highly sensitive to environmental cues and are implicated in both detrimental and protective outcomes during autoimmune demyelination. Experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice expressing signaling defective dominant-negative interferon gamma (IFN-γ) receptors on astrocytes to determine the influence of inflammation on astrocyte activity. Inhibition of IFN-γ signaling to astrocytes did not influence disease incidence, onset, initial progression of symptoms, blood brain barrier (BBB) integrity or the composition of the acute CNS inflammatory response. Nevertheless, increased demyelination at peak acute disease in the absence of IFN-γ signaling to astrocytes correlated with sustained clinical symptoms. Following peak disease, diminished clinical remission, increased mortality and sustained astrocyte activation within the gray matter demonstrate a critical role of IFN-γ signaling to astrocytes in neuroprotection. Diminished disease remission was associated with escalating demyelination, axonal degeneration and sustained inflammation. The CNS infiltrating leukocyte composition was not altered; however, decreased IL-10 and IL-27 correlated with sustained disease. These data indicate that astrocytes play a critical role in limiting CNS autoimmune disease dependent upon a neuroprotective signaling pathway mediated by engagement of IFN-γ receptors.",2012 Jul 27,"['Hindinger, Claudia', 'Bergmann, Cornelia C.', 'Hinton, David R.', 'Phares, Timothy W.', 'Parra, Gabriel I.', 'Hussain, Shabbir', 'Savarin, Carine', 'Atkinson, Roscoe D.', 'Stohlman, Stephen A.']",PLoS One,,,True
bf0c3f90978f7e4794dfe1dd2d90ddb592fc6549,PMC,Influence of Mabs on PrP(Sc) Formation Using In Vitro and Cell-Free Systems,http://dx.doi.org/10.1371/journal.pone.0041626,PMC3407222,22848548,CC BY,"PrP(Sc) is believed to serve as a template for the conversion of PrP(C) to the abnormal isoform. This process requires contact between the two proteins and implies that there may be critical contact sites that are important for conversion. We hypothesized that antibodies binding to either PrP(c)or PrP(Sc) would hinder or prevent the formation of the PrP(C)–PrP(Sc) complex and thus slow down or prevent the conversion process. Two systems were used to analyze the effect of different antibodies on PrP(Sc) formation: (i) neuroblastoma cells persistently infected with the 22L mouse-adapted scrapie stain, and (ii) protein misfolding cyclic amplification (PMCA), which uses PrP(Sc) as a template or seed, and a series of incubations and sonications, to convert PrP(C) to PrP(Sc). The two systems yielded similar results, in most cases, and demonstrate that PrP-specific monoclonal antibodies (Mabs) vary in their ability to inhibit the PrP(C)–PrP(Sc) conversion process. Based on the numerous and varied Mabs analyzed, the inhibitory effect does not appear to be epitope specific, related to PrP(C) conformation, or to cell membrane localization, but is influenced by the targeted PrP region (amino vs carboxy).",2012 Jul 27,"['Chang, Binggong', 'Petersen, Robert', 'Wisniewski, Thomas', 'Rubenstein, Richard']",PLoS One,,,True
8a2fd6ad99f53bb749e4ccaf50fdd36a14bd4aba,PMC,Photodynamic Inactivation of Mammalian Viruses and Bacteriophages,http://dx.doi.org/10.3390/v4071034,PMC3407894,22852040,CC BY,"Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.",2012 Jun 26,"['Costa, Liliana', 'Faustino, Maria Amparo F.', 'Neves, Maria Graça P. M. S.', 'Cunha, Ângela', 'Almeida, Adelaide']",Viruses,,,True
4b3ddd160ebda77b58843d167709d71a73a3bf4a,PMC,Legume Lectins Inhibit Human Parainfluenza Virus Type 2 Infection by Interfering with the Entr,http://dx.doi.org/10.3390/v4071104,PMC3407897,22852043,CC BY,"Three lectins with different sugar binding specificities were investigated for anti-viral activity against human parainfluenza virus type 2 (hPIV-2). The lectins, concanavalin A (Con A), lens culinaris agglutinin (LCA) and peanut agglutinin (PNA), inhibited cell fusion and hemadsorption induced by hPIV-2. Virus nucleoprotein (NP) gene synthesis was largely inhibited, but fusion (F) and hemagglutinin-neuraminidase (HN) gene syntheses were not. An indirect immunofluorescence study showed that Con A inhibited virus NP, F and HN protein syntheses, but LCA did not completely inhibit them, and that PNA inhibited only NP protein synthesis. Using a recombinant green fluorescence protein-expressing hPIV-2, without matrix protein (rghPIV-2ΔM), it was found that virus entry into the cells was not completely prevented. The lectins considerably reduced the number of viruses released compared with that of virus infected cells. The lectins bound to cell surface within 10 min, and many aggregates were observed at 30 min. Con A and LCA slightly disrupted actin microfilaments and microtubules, but PNA had almost no effect on them. These results indicated that the inhibitory effects of the lectins were caused mainly by the considerable prevention of virus adsorption to the cells by the lectin binding to their receptors.",2012 Jun 29,"['Uematsu, Jun', 'Koyama, Aoi', 'Takano, Sayaka', 'Ura, Yukari', 'Tanemura, Miho', 'Kihira, Sahoko', 'Yamamoto, Hidetaka', 'Kawano, Mitsuo', 'Tsurudome, Masato', 'O’Brien, Myles', 'Komada, Hiroshi']",Viruses,,,True
7ed71c815f2ddd8160be8a574698fe6685fe9dda,PMC,Algal Lectins as Potential HIV Microbicide Candidates,http://dx.doi.org/10.3390/md10071476,PMC3407925,22851920,CC BY,"The development and use of topical microbicides potentially offers an additional strategy to reduce the spread of the Human Immunodeficiency Virus (HIV). Carbohydrate-binding agents (CBAs) that show specificity for high mannose carbohydrates on the surface of the heavily glycosylated envelope of HIV are endowed with potent anti-HIV activity. In fact, a number of algal lectins such as cyanovirin-N, microvirin, microcystis viridis lectin, scytovirin, Oscillatoria agardhii agglutinin and griffithsin are considered as potential microbicide candidates to prevent the sexual transmission of HIV through topical applications. They not only inhibit infection of cells by cell-free virus but they can also efficiently prevent virus transmission from virus-infected cells to uninfected CD4(+) target T-lymphocytes and DC-SIGN-directed capture of HIV-1 and transmission to CD4(+) T lymphocytes. This review focuses on the structural properties and carbohydrate specificity of these algal lectins, their antiviral activity against HIV and several other enveloped viruses, their safety profile and viral resistance patterns.",2012 Jul 10,"['Huskens, Dana', 'Schols, Dominique']",Mar Drugs,,,True
074a37594f93652c9db7cef967b21eaa5b70f731,PMC,Extracellular Vesicles and Their Convergence with Viral Pathways,http://dx.doi.org/10.1155/2012/767694,PMC3410301,22888349,CC BY,"Extracellular vesicles (microvesicles), such as exosomes and shed microvesicles, contain a variety of molecules including proteins, lipids, and nucleic acids. Microvesicles appear mostly to originate from multivesicular bodies or to bud from the plasma membrane. Here, we review the convergence of microvesicle biogenesis and aspects of viral assembly and release pathways. Herpesviruses and retroviruses, amongst others, recruit several elements from the microvesicle biogenesis pathways for functional virus release. In addition, noninfectious pleiotropic virus-like vesicles can be released, containing viral and cellular components. We highlight the heterogeneity of microvesicle function during viral infection, addressing microvesicles that can either block or enhance infection, or cause immune dysregulation through bystander action in the immune system. Finally, endogenous retrovirus and retrotransposon elements deposited in our genomes millions of years ago can be released from cells within microvesicles, suggestive of a viral origin of the microvesicle system or perhaps of an evolutionary conserved system of virus-vesicle codependence. More research is needed to further elucidate the complex function of the various microvesicles produced during viral infection, possibly revealing new therapeutic intervention strategies.",2012 Jul 25,"['Wurdinger, Thomas', 'Gatson, NaTosha N.', 'Balaj, Leonora', 'Kaur, Balveen', 'Breakefield, Xandra O.', 'Pegtel, D. Michiel']",Adv Virol,,,True
b9a8782661a61d1562b8d6a2098fd35c76b35349,PMC,"Origin, diversity, and maturation of human antiviral antibodies analyzed by high-throughput sequencing",http://dx.doi.org/10.3389/fmicb.2012.00277,PMC3410596,22876240,CC BY,"Our understanding of how antibodies are generated and function could help develop effective vaccines and antibody-based therapeutics against viruses such as HIV-1, SARS coronavirus (SARS CoV), and Hendra and Nipah viruses (henipaviruses). Although broadly neutralizing antibodies (bnAbs) against the HIV-1 were observed in patients, elicitation of such bnAbs remains a major challenge when compared to other viral targets. We previously hypothesized that HIV-1 could have evolved a strategy to evade the immune system due to absent or very weak binding of germline antibodies to the conserved epitopes that may not be sufficient to initiate and/or maintain an effective immune response. To further explore our hypothesis, we used the 454 sequence analysis of a large naïve library of human IgM antibodies which had been used for selecting antibodies against SARS CoV receptor-binding domain (RBD), and soluble G proteins (sG) of henipaviruses. We found that the human IgM repertoires from the 454 sequencing have diverse germline usages, recombination patterns, junction diversity, and a lower extent of somatic mutation. In this study, we identified antibody maturation intermediates that are related to bnAbs against the HIV-1 and other viruses as observed in normal individuals, and compared their genetic diversity and somatic mutation level along with available structural and functional data. Further computational analysis will provide framework for understanding the underlying genetic and molecular determinants related to maturation pathways of antiviral bnAbs that could be useful for applying novel approaches to the design of effective vaccine immunogens and antibody-based therapeutics.",2012 Aug 2,"['Prabakaran, Ponraj', 'Zhu, Zhongyu', 'Chen, Weizao', 'Gong, Rui', 'Feng, Yang', 'Streaker, Emily', 'Dimitrov, Dimiter S.']",Front Microbiol,,,True
4e8f8ad6957ffac26673761935854e6c05b7768e,PMC,Structural Bases of Coronavirus Attachment to Host Aminopeptidase N and Its Inhibition by Neutralizing Antibodies,http://dx.doi.org/10.1371/journal.ppat.1002859,PMC3410853,22876187,CC BY,"The coronaviruses (CoVs) are enveloped viruses of animals and humans associated mostly with enteric and respiratory diseases, such as the severe acute respiratory syndrome and 10–20% of all common colds. A subset of CoVs uses the cell surface aminopeptidase N (APN), a membrane-bound metalloprotease, as a cell entry receptor. In these viruses, the envelope spike glycoprotein (S) mediates the attachment of the virus particles to APN and subsequent cell entry, which can be blocked by neutralizing antibodies. Here we describe the crystal structures of the receptor-binding domains (RBDs) of two closely related CoV strains, transmissible gastroenteritis virus (TGEV) and porcine respiratory CoV (PRCV), in complex with their receptor, porcine APN (pAPN), or with a neutralizing antibody. The data provide detailed information on the architecture of the dimeric pAPN ectodomain and its interaction with the CoV S. We show that a protruding receptor-binding edge in the S determines virus-binding specificity for recessed glycan-containing surfaces in the membrane-distal region of the pAPN ectodomain. Comparison of the RBDs of TGEV and PRCV to those of other related CoVs, suggests that the conformation of the S receptor-binding region determines cell entry receptor specificity. Moreover, the receptor-binding edge is a major antigenic determinant in the TGEV envelope S that is targeted by neutralizing antibodies. Our results provide a compelling view on CoV cell entry and immune neutralization, and may aid the design of antivirals or CoV vaccines. APN is also considered a target for cancer therapy and its structure, reported here, could facilitate the development of anti-cancer drugs.",2012 Aug 2,"['Reguera, Juan', 'Santiago, César', 'Mudgal, Gaurav', 'Ordoño, Desiderio', 'Enjuanes, Luis', 'Casasnovas, José M.']",PLoS Pathog,,,True
7be0c55fb0d4bb5983591cdc5366c67d44aa1b4e,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,True
330375e29f69eec6317d4345ed4b50d6553da5e3,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
c6dd496de1c9cadd8d7651bc0b7f4602e493d1c0,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
4d49eed1f9b06bc2de53ac19343bb801847519f1,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
6384cba77fb5c04cba53395d4f066735ec627b50,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
94114dda8bad56f55e93e709f8f5bec01227daf5,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
630c673ca40e5d3d5e7da8e1291e1d1905932602,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
872453c36fd9e95774cca279e4ddbf8d3d42ff8b,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
ccac686a6e523c29bbc10c1902aa9403baf19c7a,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
9400c1add999936c5156c79274d804113841c641,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
d75571144654e55a962409ab789839f59f7e772d,PMC,Canine Hepacivirus NS3 Serine Protease Can Cleave the Human Adaptor Proteins MAVS and TRIF,http://dx.doi.org/10.1371/journal.pone.0042481,PMC3411667,22870331,CC BY,"Canine hepacivirus (CHV) was recently identified in domestic dogs and horses. The finding that CHV is genetically the virus most closely related to hepatitis C virus (HCV) has raised the question of whether HCV might have evolved as the result of close contact between dogs and/or horses and humans. The aim of this study was to investigate whether the NS3/4A serine protease of CHV specifically cleaves human mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF). The proteolytic activity of CHV NS3/4A was evaluated using a bacteriophage lambda genetic screen. Human MAVS- and TRIF-specific cleavage sites were engineered into the lambda cI repressor. Upon infection of Escherichia coli cells coexpressing these repressors and a CHV NS3/4A construct, lambda phage replicated up to 2000-fold more efficiently than in cells expressing a CHV protease variant carrying the inactivating substitution S139A. Comparable results were obtained when several HCV NS3/4A constructs of genotype 1b were assayed. This indicates that CHV can disrupt the human innate antiviral defense signaling pathway and suggests a possible evolutionary relationship between CHV and HCV.",2012 Aug 1,"['Parera, Mariona', 'Martrus, Gloria', 'Franco, Sandra', 'Clotet, Bonaventura', 'Martinez, Miguel Angel']",PLoS One,,,True
8e16bcce21552d6bb63b2407557f0a8dbd8b007e,PMC,High Rates of Detection of Respiratory Viruses in Tonsillar Tissues from Children with Chronic Adenotonsillar Disease,http://dx.doi.org/10.1371/journal.pone.0042136,PMC3411673,22870291,CC BY,"Chronic tonsillar diseases are an important health problem, leading to large numbers of surgical procedures worldwide. Little is known about pathogenesis of these diseases. In order to investigate the role of respiratory viruses in chronic adenotonsillar diseases, we developed a cross-sectional study to determine the rates of viral detections of common respiratory viruses detected by TaqMan real time PCR (qPCR) in nasopharyngeal secretions, tonsillar tissues and peripheral blood from 121 children with chronic tonsillar diseases, without symptoms of acute respiratory infections. At least one respiratory virus was detected in 97.5% of patients. The viral co-infection rate was 69.5%. The most frequently detected viruses were human adenovirus in 47.1%, human enterovirus in 40.5%, human rhinovirus in 38%, human bocavirus in 29.8%, human metapneumovirus in 17.4% and human respiratory syncytial virus in 15.7%. Results of qPCR varied widely between sample sites: human adenovirus, human bocavirus and human enterovirus were predominantly detected in tissues, while human rhinovirus was more frequently detected in secretions. Rates of virus detection were remarkably high in tonsil tissues: over 85% in adenoids and close to 70% in palatine tonsils. In addition, overall virus detection rates were higher in more hypertrophic than in smaller adenoids (p = 0.05), and in the particular case of human enteroviruses, they were detected more frequently (p = 0.05) in larger palatine tonsils than in smaller ones. While persistence/latency of DNA viruses in tonsillar tissues has been documented, such is not the case of RNA viruses. Respiratory viruses are highly prevalent in adenoids and palatine tonsils of patients with chronic tonsillar diseases, and persistence of these viruses in tonsils may stimulate chronic inflammation and play a role in the pathogenesis of these diseases.",2012 Aug 3,"['Proenca-Modena, Jose Luiz', 'Pereira Valera, Fabiana Cardoso', 'Jacob, Marcos Gerhardinger', 'Buzatto, Guilherme Pietrucci', 'Saturno, Tamara Honorato', 'Lopes, Lucia', 'Souza, Jamila Mendonça', 'Paula, Flavia Escremim', 'Silva, Maria Lucia', 'Carenzi, Lucas Rodrigues', 'Tamashiro, Edwin', 'Arruda, Eurico', 'Anselmo-Lima, Wilma Terezinha']",PLoS One,,,True
692088c942db684cd4e1ec03c927eb3ae6f6caf6,PMC,Association of Fcγ Receptor IIB Polymorphism with Cryptococcal Meningitis in HIV-Uninfected Chinese Patients,http://dx.doi.org/10.1371/journal.pone.0042439,PMC3411792,22879986,CC BY,"BACKGROUND: As important regulators of the immune system, the human Fcγ receptors (FcγRs) have been demonstrated to play important roles in the pathogenesis of various infectious diseases. The aim of the present study was to identify the association between FCGR polymorphisms and cryptococcal meningitis. METHODOLOGY/PRINCIPAL FINDINGS: In this case control genetic association study, we genotyped four functional polymorphisms in low-affinity FcγRs, including FCGR2A 131H/R, FCGR3A 158F/V, FCGR3B NA1/NA2, and FCGR2B 232I/T, in 117 patients with cryptococcal meningitis and 190 healthy controls by multiplex SNaPshot technology. Among the 117 patients with cryptococcal meningitis, 59 had predisposing factors. In patients with cryptococcal meningitis, the FCGR2B 232I/I genotype was over-presented (OR = 1.652, 95% CI [1.02–2.67]; P = 0.039) and the FCGR2B 232I/T genotype was under-presented (OR = 0.542, 95% CI [0.33–0.90]; P = 0.016) in comparison with control group. In cryptococcal meningitis patients without predisposing factors, FCGR2B 232I/I genotype was also more frequently detected (OR = 1.958, 95% CI [1.05–3.66]; P = 0.033), and the FCGR2B 232I/T genotype was also less frequently detected (OR = 0.467, 95% CI [0.24–0.91]; P = 0.023) than in controls. No significant difference was found among FCGR2A 131H/R, FCGR3A 158F/V, and FCGR3B NA1/NA2 genotype frequencies between patients and controls. CONCLUSION/SIGNIFICANCE: We found for the first time associations between cryptococcal meningitis and FCGR2B 232I/T genotypes, which suggested that FcγRIIB might play an important role in the central nervous system infection by Cryptococcus in HIV-uninfected individuals.",2012 Aug 3,"['Hu, Xiu-Ping', 'Wu, Ji-Qin', 'Zhu, Li-Ping', 'Wang, Xuan', 'Xu, Bin', 'Wang, Rui-Ying', 'Ou, Xue-Ting', 'Weng, Xin-Hua']",PLoS One,,,True
ca57f284dbad5683f531ee130483ca080a1f2d98,PMC,IL-10 Mediated Regulation of Liver Inflammation during Acute Murine Cytomegalovirus Infection,http://dx.doi.org/10.1371/journal.pone.0042850,PMC3411849,22880122,CC BY,"Various cell types in both lymphoid and non-lymphoid tissues produce the anti-inflammatory cytokine interleukin (IL)-10 during murine cytomegalovirus (MCMV) infection. The functions of IL-10 in the liver during acute infection and the cells that generate this cytokine at this site have not been extensively investigated. In this study, we demonstrate that the production of IL-10 in the liver is elevated in C57BL/6 mice during late acute MCMV infection. Using IL-10 green fluorescence protein (GFP) reporter knock-in mice, designated IL-10-internal ribosomal entry site (IRES)-GFP-enhanced reporter (tiger), NK cells are identified as major IL-10 expressing cells in the liver after infection, along with T cells and other leukocytes. In the absence of IL-10, mice exhibit marked elevations in proinflammatory cytokines and in the numbers of mononuclear cells and lymphocytes infiltrating the liver during this infection. IL-10-deficiency also enhances liver injury without improving viral clearance from this site. Collectively, the results indicate that IL-10-producing cells in the liver provide protection from collateral injury by modulating the inflammatory response associated with MCMV infection.",2012 Aug 3,"['Gaddi, Pamela J.', 'Crane, Meredith J.', 'Kamanaka, Masahito', 'Flavell, Richard A.', 'Yap, George S.', 'Salazar-Mather, Thais P.']",PLoS One,,,True
9009370b71d913612356de26f968966c3399da2d,PMC,Proteomic analysis of purified Newcastle disease virus particles,http://dx.doi.org/10.1186/1477-5956-10-32,PMC3413529,22571704,CC BY,"BACKGROUND: Newcastle disease virus (NDV) is an enveloped RNA virus, bearing severe economic losses to the poultry industry worldwide. Previous virion proteomic studies have shown that enveloped viruses carry multiple host cellular proteins both internally and externally during their life cycle. To address whether it also occurred during NDV infection, we performed a comprehensive proteomic analysis of highly purified NDV La Sota strain particles. RESULTS: In addition to five viral structural proteins, we detected thirty cellular proteins associated with purified NDV La Sota particles. The identified cellular proteins comprised several functional categories, including cytoskeleton proteins, annexins, molecular chaperones, chromatin modifying proteins, enzymes-binding proteins, calcium-binding proteins and signal transduction-associated proteins. Among these, three host proteins have not been previously reported in virions of other virus families, including two signal transduction-associated proteins (syntenin and Ras small GTPase) and one tumor-associated protein (tumor protein D52). The presence of five selected cellular proteins (i.e., β-actin, tubulin, annexin A2, heat shock protein Hsp90 and ezrin) associated with the purified NDV particles was validated by Western blot or immunogold labeling assays. CONCLUSIONS: The current study presented the first standard proteomic profile of NDV. The results demonstrated the incorporation of cellular proteins in NDV particles, which provides valuable information for elucidating viral infection and pathogenesis.",2012 May 9,"['Ren, Xiangpeng', 'Xue, Chunyi', 'Kong, Qingming', 'Zhang, Chengwen', 'Bi, Yingzuo', 'Cao, Yongchang']",Proteome Sci,,,True
9491f89b53c527904943035f8b4a1f997c3609ad,PMC,Elevated levels of vitamin D and deficiency of mannose binding lectin in dengue hemorrhagic fever,http://dx.doi.org/10.1186/1743-422X-9-86,PMC3413536,22559908,CC BY,"BACKGROUND: Altered plasma concentrations of vitamin D and mannose binding lectin (MBL), components of innate immunity, have been shown to be associated with the pathogenesis of viral infections. The objective of the present study was to find out whether plasma concentrations of MBL and vitamin D are different in patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). THE RESULTS: The plasma concentrations of vitamin D and MBL were assessed in 48 DF cases, 45 DHF cases and 20 apparently healthy controls using ELISA based methods. Vitamin D concentrations were found to be higher among both DF and DHF cases as compared to healthy controls (P < 0.005 and P < 0.001). Vitamin D concentrations were not different between DF and DHF cases. When the dengue cases were classified into primary and secondary infections, secondary DHF cases had significantly higher concentrations of vitamin D as compared to secondary DF cases (P < 0.050). MBL concentrations were not significantly different between healthy controls and dengue cases. MBL concentrations were observed to be lower in DHF cases as compared to DF cases (P < 0.050). Although MBL levels were not different DF and DHF cases based on immune status, the percentage of primary DHF cases (50%) having MBL levels lower than 500 ng/ml were less compared to primary DF cases (P = 0.038). CONCLUSIONS: The present study suggests that higher concentrations of vitamin D might be associated with secondary DHF while deficiency of MBL may be associated with primary DHF.",2012 May 4,"['Alagarasu, Kalichamy', 'Bachal, Rupali V', 'Bhagat, Asha B', 'Shah, Paresh S', 'Dayaraj, Cecilia']",Virol J,,,True
8a2d2e38286fa86dcf60a8a1b0b95658f2d70850,PMC,"Surveillance of Community Outbreaks of Respiratory Tract Infections Based on House-Call Visits in the Metropolitan Area of Athens, Greece",http://dx.doi.org/10.1371/journal.pone.0040310,PMC3414488,22905091,CC BY,"BACKGROUND: The traditional Serfling-type approach for influenza-like illness surveillance requires long historical time-series. We retrospectively evaluated the use of recent, short, historical time-series for recognizing the onset of community outbreaks of respiratory tract infections (RTIs). METHODS: The data used referred to the proportion of diagnoses for upper or lower RTIs to total diagnoses for house-call visits, performed by a private network of medical specialists (SOS Doctors) in the metropolitan area of Athens, Greece, between January 01, 2000 and October 12, 2008. The reference standard classification of the observations was obtained by generating epidemic thresholds after analyzing the full 9-year period. We evaluated two different alert generating methods [simple regression and cumulative sum (CUSUM), respectively], under a range of input parameters, using data for the previous running 4–6 week period. These methods were applied if the previous weeks contained non-aberrant observations. RESULTS: We found that the CUSUM model with a specific set of parameters performed marginally better than simple regression for both groups. The best results (sensitivity, specificity) for simple regression and CUSUM models for upper RTIs were (1.00, 0.82) and (0.94, 0.93) respectively. Corresponding results for lower RTIs were (1.00, 0.80) and (0.93, 0.91) respectively. CONCLUSIONS: Short-term data for house-call visits can be used rather reliably to identify respiratory tract outbreaks in the community using simple regression and CUSUM methods. Such surveillance models could be particularly useful when a large historical database is either unavailable or inaccurate and, thus, traditional methods are not optimal.",2012 Aug 8,"['Spanos, Alex', 'Theocharis, George', 'Karageorgopoulos, Drosos E.', 'Peppas, George', 'Fouskakis, Dimitris', 'Falagas, Matthew E.']",PLoS One,,,True
965f06d2f9a87b69f59b1656c979e04eaa5d75be,PMC,"Comparison of Temporal and Spatial Dynamics of Seasonal H3N2, Pandemic H1N1 and Highly Pathogenic Avian Influenza H5N1 Virus Infections in Ferrets",http://dx.doi.org/10.1371/journal.pone.0042343,PMC3414522,22905124,CC BY,"Humans may be infected by different influenza A viruses—seasonal, pandemic, and zoonotic—which differ in presentation from mild upper respiratory tract disease to severe and sometimes fatal pneumonia with extra-respiratory spread. Differences in spatial and temporal dynamics of these infections are poorly understood. Therefore, we inoculated ferrets with seasonal H3N2, pandemic H1N1 (pH1N1), and highly pathogenic avian H5N1 influenza virus and performed detailed virological and pathological analyses at time points from 0.5 to 14 days post inoculation (dpi), as well as describing clinical signs and hematological parameters. H3N2 infection was restricted to the nose and peaked at 1 dpi. pH1N1 infection also peaked at 1 dpi, but occurred at similar levels throughout the respiratory tract. H5N1 infection occurred predominantly in the alveoli, where it peaked for a longer period, from 1 to 3 dpi. The associated lesions followed the same spatial distribution as virus infection, but their severity peaked between 1 and 6 days later. Neutrophil and monocyte counts in peripheral blood correlated with inflammatory cell influx in the alveoli. Of the different parameters used to measure lower respiratory tract disease, relative lung weight and affected lung tissue allowed the best quantitative distinction between the virus groups. There was extra-respiratory spread to more tissues—including the central nervous system—for H5N1 infection than for pH1N1 infection, and to none for H3N2 infection. This study shows that seasonal, pandemic, and zoonotic influenza viruses differ strongly in the spatial and temporal dynamics of infection in the respiratory tract and extra-respiratory tissues of ferrets.",2012 Aug 8,"['van den Brand, Judith M. A.', 'Stittelaar, Koert J.', 'van Amerongen, Geert', 'Reperant, Leslie', 'de Waal, Leon', 'Osterhaus, Albert D. M. E.', 'Kuiken, Thijs']",PLoS One,,,True
25bdd8095f71bd8c6be54898b437e16896ea3790,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,True
f6b8e6990b4e61f4ad98912a5e7ff3455a29d4fc,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
fa8acd41911709dbc9a9b04880149e7a5150ec10,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
c0b1a91e05ba4ff782360a2afb1f89d61e7c5c47,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
4b0e2a496f34d37b1f28083127273d0b8259a354,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
d0d24fc6d2f8e2d91515881ee713162099aeb747,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
483dbb727c11ddbd2609959ef30c08c5389f3cfb,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
4c102c3cb5e7aed5cb9214d7b2bd00524d839d8f,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
d573d37a7a32303177ee7022b5cf1d3b8af5358a,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
43f8af861c5d5c65564a30bcf9627985eb15a3dc,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
656d6bf0f5b0f360d55d5321e0c305eb6a12cbab,PMC,IFN-γ protects from lethal IL-17 mediated viral encephalomyelitis independent of neutrophils,http://dx.doi.org/10.1186/1742-2094-9-104,PMC3419086,22642802,CC BY,"BACKGROUND: The interplay between IFN-γ, IL-17 and neutrophils during CNS inflammatory disease is complex due to cross-regulatory factors affecting both positive and negative feedback loops. These interactions have hindered the ability to distinguish the relative contributions of neutrophils, Th1 and Th17 cell-derived effector molecules from secondary mediators to tissue damage and morbidity. METHODS: Encephalitis induced by a gliatropic murine coronavirus was used as a model to assess the direct contributions of neutrophils, IFN-γ and IL-17 to virus-induced mortality. CNS inflammatory conditions were selectively manipulated by adoptive transfer of virus-primed wild-type (WT) or IFN-γ deficient (GKO) memory CD4(+) T cells into infected SCID mice, coupled with antibody-mediated neutrophil depletion and cytokine blockade. RESULTS: Transfer of GKO memory CD4(+) T cells into infected SCID mice induced rapid mortality compared to recipients of WT memory CD4(+) T cells, despite similar virus control and demyelination. In contrast to recipients of WT CD4(+) T cells, extensive neutrophil infiltration and IL-17 expression within the CNS in recipients of GKO CD4(+) T cells provided a model to directly assess their contribution(s) to disease. Recipients of WT CD4(+) T cells depleted of IFN-γ did not express IL-17 and were spared from mortality despite abundant CNS neutrophil infiltration, indicating that mortality was not mediated by excessive CNS neutrophil accumulation. By contrast, IL-17 depletion rescued recipients of GKO CD4(+) T cells from rapid mortality without diminishing neutrophils or reducing GM-CSF, associated with pathogenic Th17 cells in CNS autoimmune models. Furthermore, co-transfer of WT and GKO CD4(+) T cells prolonged survival in an IFN-γ dependent manner, although IL-17 transcription was not reduced. CONCLUSIONS: These data demonstrate that IL-17 mediates detrimental clinical consequences in an IFN-γ-deprived environment, independent of extensive neutrophil accumulation or GM-CSF upregulation. The results also suggest that IFN-γ overrides the detrimental IL-17 effector responses via a mechanism downstream of transcriptional regulation.",2012 May 29,"['Savarin, Carine', 'Stohlman, Stephen A', 'Hinton, David R', 'Ransohoff, Richard M', 'Cua, Daniel J', 'Bergmann, Cornelia C']",J Neuroinflammation,,,True
7366b56a55321eebcb1d38074932d23ad4346038,PMC,Novel Virostatic Agents against Bluetongue Virus,http://dx.doi.org/10.1371/journal.pone.0043341,PMC3419696,22905259,CC BY,"Bluetongue virus (BTV), a member in the family Reoviridae, is a re-emerging animal disease infecting cattle and sheep. With its recent outbreaks in Europe, there is a pressing need for efficacious antivirals. We presented here the identification and characterization of a novel virostatic molecule against BTV, an aminothiophenecarboxylic acid derivative named compound 003 (C003). The virostatic efficacy of C003 could be improved via chemical modification, leading to a de novo synthesized compound 052 (C052). The 50% effective concentrations (EC(50)) of C003 and C052 were determined at 1.76±0.73 µM and 0.27±0.12 µM, respectively. The 50% cytotoxicity concentration (CC(50)) of C003 was over 100 µM and the CC(50) of C052 was at 82.69 µM. Accordingly, the 50% selective index (SI(50)) of C003 and C052 against BTV was over 57 and 306, respectively. The inhibitory effect of C003/C052 on BTV-induced apoptosis was also confirmed via the inhibition of caspase-3/-7 activation post BTV infection. C003/C052 could inhibit BTV induced CPE even when added as late as 24 h.p.i., indicating that they might act at late stage of viral life-cycle. C003/C052 could reduce over two-logs of both the progeny virus production and the number of genomic viral RNA copies. Interestingly, both the activation of host autophagy and viral protein expression were inhibited post BTV infection when cells were treated with C003 and C052, suggesting that C003/C052 might act as virostatic agents via inhibiting host autophagy activation. Although further investigations might be needed to pin down the exact mechanism of C003/C052, our finding suggested that these compounds might be potent lead compounds with potential novel mechanism of action against BTV.",2012 Aug 15,"['Gu, Linlin', 'Musiienko, Volodymyr', 'Bai, Zhijun', 'Qin, Aijian', 'Schneller, Stewart W.', 'Li, Qianjun']",PLoS One,,,True
6ab7d80bb6dc14cac7fe9c7d5a6060af434bef0a,PMC,"In young children, persistent wheezing is associated with bronchial bacterial infection: a retrospective analysis",http://dx.doi.org/10.1186/1471-2431-12-83,PMC3420249,22726254,CC BY,"BACKGROUND: Young children with persistent wheezing pose a diagnostic and therapeutical challenge to the pediatrician. We aimed to evaluate bacterial bronchial infection as a possible reason for non response to conventional asthma therapy, and to identify and characterise the predominant pathogens involved. METHODS: We retrospectively analysed microbiological and cytological findings in a selected population of young wheezers with symptoms unresponsive to inhaled corticosteroid (ICS) therapy, who underwent flexible bronchoscopy with bronchoalveolar lavage (BAL). Procedural measures were taken to limit contamination risk and quantitative bacterial culture of BAL fluid (significance cut-off ≥ 10(4) colony-forming units/ml) was used. Modern microbiological methods were used for detection of a wide panel of pathogens and for characterisation of the bacterial isolates. RESULTS: 33 children aged between 4 and 38 months, without structural anomalies of the conductive airways were evaluated. Significant bacterial BAL cultures were found in 48,5 % of patients. Haemophilus influenzae was isolated in 30,3 %, Streptococcus pneumoniae in 12,1 % and Moraxella catarrhalis in 12,1 %. All H. influenzae isolates were non-encapsulated strains and definitely distinguished from non-haemolytic H. haemolyticus. Respiratory viruses were detected in 21,9 % of cases with mixed bacterial-viral infection in 12,1 %. Cytology revealed a marked neutrophilic inflammation. CONCLUSIONS: Bacterial infection of the bronchial tree is common in persistent preschool wheezers and provides a possible explanation for non response to ICS therapy. Non-typeable H. influenzae seems to be the predominant pathogen involved, followed by S. pneumoniae and M. catarrhalis.",2012 Jun 22,"['De Schutter, Iris', 'Dreesman, Alexandra', 'Soetens, Oriane', 'De Waele, Marc', 'Crokaert, Françoise', 'Verhaegen, Jan', 'Piérard, Denis', 'Malfroot, Anne']",BMC Pediatr,,,True
845bf0e6613fbb4dfd669bd913f7ebe6020b2cf4,PMC,Acute Fibrinous and Organizing Pneumonia and Undifferentiated Connective Tissue Disease: A Case Report,http://dx.doi.org/10.1155/2012/549298,PMC3420729,22957292,CC BY,"Acute fibrinous and organizing pneumonia (AFOP), recently described, is a histologic pattern characterized by the presence of fibrin “balls” within alveolar spaces. The term undifferentiated connective tissue disease (UCTD) is used to identify autoimmune systemic diseases that do not fulfill the criteria to be classified as a definitive connective tissue disease. The AFOP has never been reported in association with UCTD. The present reported case is a 39-year-old Caucasian, female with dry cough and progressive dyspnea. Eight months later, she was diagnosed with “organizing pneumonia” based on clinical history and radiologic images. She manifested Raynaud's Phenomenon, sicca syndrome, boot and gloves neuropathic pain, and previous hypothyroidism. Antinuclear antibody, rheumatoid factor, and specific autoantibodies were negative. Salivary gland biopsy and electroneuromyiography were normal. The capillaroscopy showed a “scleroderma” pattern with capillary deletion and ectasia. She experienced clinical and radiologic worsening. Despite being submitted to cyclophosphamide pulse, she developed hemorrhage and then died. Thoracotomy pulmonary specimen showed histological pattern of AFOP. This paper shows a rare association of AFOP with UCTD.",2012 Apr 4,"['Valim, Valéria', 'Rocha, Roberta Hora', 'Couto, Roberta Barcelos', 'Paixão, Thaysa Simões', 'Serrano, Érica Vieira']",Case Rep Rheumatol,,,True
2e5bfe1233f49b63cd653c03a695b24f42adaedd,PMC,Novel Method for Isolation of Murine Clara Cell Secretory Protein-Expressing Cells with Traces of Stemness,http://dx.doi.org/10.1371/journal.pone.0043008,PMC3420884,22916196,CC0,"Clara cells are non-ciliated, secretory bronchiolar epithelial cells that serve to detoxify harmful inhaled substances. Clara cells also function as stem/progenitor cells for repair in the bronchioles. Clara cell secretory protein (CCSP) is specifically expressed in pulmonary Clara cells and is widely used as a Clara cell marker. In addition CCSP promoter is commonly used to direct gene expression into the lung in transgenic models. The discovery of CCSP immunoreactivity in plasma membranes of airway lining cells prompted us to explore the possibility of enriching Clara cells by flow cytometry. We established a novel and simple method for the isolation of CCSP-expressing cell Clara cells using a combination of mechanical and enzymatic dissociation followed by flow cytometry sorting technology. We showed that ∼25% of dissociated cells from whole lung expressed CCSP. In the resulting preparation, up to 98% of cells expressed CCSP. Notably, we found that several common stem cell markers including CD44, CD133, Sca-1 and Sox2 were expressed in CCSP(+) cells. Moreover, CCSP(+) cells were able to form spheroid colonies in vitro with 0.97‰ efficiency. Parallel studies in vivo confirmed that a small population of CCSP(−)expressing cells in mouse airways also demonstrates stem cell-like properties such as label retention and harboring rare bronchioalveolar stem cells (BASCs) in terminal bronchioles (TBs). We conclude that CCSP(+) cells exhibit a number of stem cell-like features including stem cell marker expression, bronchosphere colony formation and self-renewal ability. Clara cell isolation by flow cytometry sorting is a useful method for investigating the function of primary Clara cells in stem cell research and mouse models.",2012 Aug 16,"['Wang, Xiao-Yang', 'Keefe, Kathleen M.', 'Jensen-Taubman, Sandra M.', 'Yang, Danlei', 'Yan, Kai', 'Linnoila, R. Ilona']",PLoS One,,,True
dcde88584805e783b69565364975fc31053b6b4e,PMC,Viral and Atypical Bacterial Etiology of Acute Respiratory Infections in Children under 5 Years Old Living in a Rural Tropical Area of Madagascar,http://dx.doi.org/10.1371/journal.pone.0043666,PMC3422262,22912897,CC BY,"BACKGROUND: In Madagascar, very little is known about the etiology and prevalence of acute respiratory infections (ARIs) in a rural tropical area. Recent data are needed to determine the viral and atypical bacterial etiologies in children with defined clinical manifestations of ARIs. METHODS: During one year, we conducted a prospective study on ARIs in children between 2 to 59 months in the community hospital of Ampasimanjeva, located in the south-east of Madagascar. Respiratory samples were analyzed by multiplex real-time RT-PCR, including 18 viruses and 2 atypical bacteria. The various episodes of ARI were grouped into four clinical manifestations with well-documented diagnosis: “Community Acquired Pneumonia”(CAP, group I), “Other acute lower respiratory infections (Other ALRIs, group II)”, “Upper respiratory tract infections with cough (URTIs with cough, group III)”and “Upper respiratory tract infections without cough (URTIs without cough, group IV)”. RESULTS: 295 children were included in the study between February 2010 and February 2011. Viruses and/or atypical bacteria respiratory pathogens were detected in 74.6% of samples, the rate of co-infection was 27.3%. Human rhinovirus (HRV; 20.5%), metapneumovirus (HMPV A/B, 13.8%), coronaviruses (HCoV, 12.5%), parainfluenza virus (HPIV, 11.8%) and respiratory syncytial virus A and B (RSV A/B, 11.8%) were the most detected. HRV was predominantly single detected (23.8%) in all the clinical groups while HMPV A/B (23.9%) was mainly related to CAP (group I), HPIV (17.3%) to the “Other ALRIs” (group II), RSV A/B (19.5%) predominated in the group “URTIs with cough” (group III) and Adenovirus (HAdV, 17.8%) was mainly detected in the “without cough” (group IV). INTERPRETATION: This study describes for the first time the etiology of respiratory infections in febrile children under 5 years in a malaria rural area of Madagascar and highlights the role of respiratory viruses in a well clinically defined population of ARIs.",2012 Aug 17,"['Hoffmann, Jonathan', 'Rabezanahary, Henintsoa', 'Randriamarotia, Martin', 'Ratsimbasoa, Arsène', 'Najjar, Josette', 'Vernet, Guy', 'Contamin, Bénédicte', 'Paranhos-Baccalà, Gláucia']",PLoS One,,,True
e6dcb411da6446850724d574d0e6bbb507a1f4ba,PMC,Development of Real-Time PCR Array for Simultaneous Detection of Eight Human Blood-Borne Viral Pathogens,http://dx.doi.org/10.1371/journal.pone.0043246,PMC3422334,22912836,CC0,"BACKGROUND: Real-time PCR array for rapid detection of multiple viral pathogens should be highly useful in cases where the sample volume and the time of testing are limited, i.e. in the eligibility testing of tissue and organ donors. FINDINGS: We developed a real-time PCR array capable of simultaneously detecting eight human viral pathogens: human immunodeficiency virus types 1 and 2 (HIV-1 and -2), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell leukemia virus-1 and -2 (HTLV-1 and -2), vaccinia virus (VACV) and West Nile virus (WNV). One hundred twenty (120) primers were designed using a combination of bioinformatics approaches, and, after experimental testing, 24 primer sets targeting eight viral pathogens were selected to set up the array with SYBR Green chemistry. The specificity and sensitivity of the virus-specific primer sets selected for the array were evaluated using analytical panels with known amounts of viruses spiked into human plasma. The array detected: 10 genome equivalents (geq)/ml of HIV-2 and HCV, 50 geq of HIV-1 (subtype B), HBV (genotype A) and WNV. It detected 100–1,000 geq/ml of plasma of HIV-1 subtypes (A – G), group N and CRF (AE and AG) isolates. Further evaluation with a panel consisting of 28 HIV-1 and HIV-2 clinical isolates revealed no cross-reactivity of HIV-1 or HIV-2 specific primers with another type of HIV. All 28 viral isolates were identified with specific primer sets targeting the most conserved genome areas. The PCR array correctly identified viral infections in a panel of 17 previously quantified clinical plasma samples positive for HIV-1, HCV or HBV at as low as several geq per PCR reaction. CONCLUSIONS: The viral array described here demonstrated adequate performance in the testing of donors’ clinical samples. Further improvement in its sensitivity for the broad spectrum of HIV-1 subtypes is under development.",2012 Aug 17,"['Pripuzova, Natalia', 'Wang, Richard', 'Tsai, Shien', 'Li, Bingjie', 'Hung, Guo-Chiuan', 'Ptak, Roger G.', 'Lo, Shyh-Ching']",PLoS One,,,True
db20be21b59adb1bac603a79aeea4154fd703db1,PMC,TcdC Does Not Significantly Repress Toxin Expression in Clostridium difficile 630ΔErm,http://dx.doi.org/10.1371/journal.pone.0043247,PMC3422341,22912837,CC BY,"In the past decade, Clostridium difficile has emerged as an important gut pathogen. Symptoms of C. difficile infection range from mild diarrhea to pseudomembranous colitis, sometimes resulting in colectomy or death. The main virulence factors of C. difficile are toxin A and toxin B. Besides the genes encoding these toxins (tcdA and tcdB), the pathogenicity locus (PaLoc) also contains genes encoding a sigma factor (tcdR) and a putative anti-sigma factor (tcdC). The important role of TcdR as a sigma factor for toxin expression is undisputed, whereas the role of TcdC as an anti-sigma factor, inhibiting toxin expression, is currently the subject of debate. To clarify the role of TcdC in toxin expression, we generated an isogenic ClosTron-based mutant of tcdC in Clostridium difficile strain 630Δ Erm (CT::tcdC) and determined the transcription levels of the PaLoc genes and the expression levels of the toxins in the wild type strain and the tcdC mutant strain. We found only minor differences in transcription levels of the PaLoc genes between the wild type and CT::tcdC strains and total toxin levels did not significantly differ either. These results suggest that in C. difficile 630Δerm TcdC is not a major regulator of toxin expression under the conditions tested.",2012 Aug 17,"['Bakker, Dennis', 'Smits, Wiep Klaas', 'Kuijper, Ed J.', 'Corver, Jeroen']",PLoS One,,,True
9c39ab56559377e3b362be55e8e989e059a01fb0,PMC,Activation of the Canonical Bone Morphogenetic Protein (BMP) Pathway during Lung Morphogenesis and Adult Lung Tissue Repair,http://dx.doi.org/10.1371/journal.pone.0041460,PMC3423416,22916109,CC BY,"Signaling by Bone Morphogenetic Proteins (BMP) has been implicated in early lung development, adult lung homeostasis and tissue-injury repair. However, the precise mechanism of action and the spatio-temporal pattern of BMP-signaling during these processes remains inadequately described. To address this, we have utilized a transgenic line harboring a BMP-responsive eGFP-reporter allele (BRE-eGFP) to construct the first detailed spatiotemporal map of canonical BMP-pathway activation during lung development, homeostasis and adult-lung injury repair. We demonstrate that during the pseudoglandular stage, when branching morphogenesis progresses in the developing lung, canonical BMP-pathway is active mainly in the vascular network and the sub-epithelial smooth muscle layer of the proximal airways. Activation of the BMP-pathway becomes evident in epithelial compartments only after embryonic day (E) 14.5 primarily in cells negative for epithelial-lineage markers, located in the proximal portion of the airway-tree, clusters adjacent to neuro-epithelial-bodies (NEBs) and in a substantial portion of alveolar epithelial cells. The pathway becomes activated in isolated E12.5 mesenchyme-free distal epithelial buds cultured in Matrigel suggesting that absence of reporter activity in these regions stems from a dynamic cross-talk between endoderm and mesenchyme. Epithelial cells with activated BMP-pathway are enriched in progenitors capable of forming colonies in three-dimensional Matrigel cultures. As lung morphogenesis approaches completion, eGFP-expression declines and in adult lung its expression is barely detectable. However, upon tissue-injury, either with naphthalene or bleomycin, the canonical BMP-pathways is re-activated, in bronchial or alveolar epithelial cells respectively, in a manner reminiscent to early lung development and in tissue areas where reparatory progenitor cells reside. Our studies illustrate the dynamic activation of canonical BMP-pathway during lung development and adult lung tissue-repair and highlight its involvement in two important processes, namely, the early development of the pulmonary vasculature and the management of epithelial progenitor pools both during lung development and repair of adult lung tissue-injury.",2012 Aug 20,"['Sountoulidis, Alexandros', 'Stavropoulos, Athanasios', 'Giaglis, Stavros', 'Apostolou, Eirini', 'Monteiro, Rui', 'Chuva de Sousa Lopes, Susana M.', 'Chen, Huaiyong', 'Stripp, Barry R.', 'Mummery, Christine', 'Andreakos, Evangelos', 'Sideras, Paschalis']",PLoS One,,,True
22d812dbf1b71eb834f1244bdd26db698fed6a34,PMC,Co-infection of broilers with Ornithobacterium rhinotracheale and H9N2 avian influenza virus,http://dx.doi.org/10.1186/1746-6148-8-104,PMC3424113,22748160,CC BY,"BACKGROUND: Since 2008, a progressive pneumonia has become prevalent in broilers and laying hens. This disease occurrs the first day after hatching and lasts more than 30 days, resulting in approximately 70% morbidity and 30% mortality in broilers. The objective of this study was to isolate and identify the pathogens that are responsible for the progressive pneumonia and establish an animal model for drug screening. RESULTS: 193 serum samples were collected from 8 intensive farms from 5 provinces in China and analysed in the current research. Our clinical survey showed that 65.2% to 100% of breeding broilers, breeding layers, broilers and laying hens were seropositive for ORT antibodies. From 8 intensive farms, six ORT isolates were identified by PCR and biochemical assays, and two H9N2 viruses were isolated. Newcastle Disease Virus (NDV) and Infectious BronchitisVirus (IBV) were excluded. Typical pneumonia and airsacculitis were observed both in broilers inoculated intraperitoneally with an ORT isolate alone and in those co-infected with ORT and H9N2 virus isolates. Specifically, the survival rate was 30%, 20%, 70%, 50% and 90% in birds inoculated with ORT+H9N2 virus, ORT followed by H9N2 virus, H9N2 virus followed by ORT, and ORT or H9N2 virus alone, respectively. CONCLUSIONS: The results of this study suggest that ORT infections of domestic poultry have been occurring frequently in China. ORT infection can induce higher economic losses and mortality if H9N2 AIV is also present. Although the isolation of ORT and H9N2 virus has been reported previously, there have been no reported co-infections of poultry with these two pathogens. This is the first report of co-infection of broilers with ORT and H9N2 virus, and this co-infection is probably associated with the outbreak of broiler airsacculitis in China, which has caused extensive economic losses.",2012 Jul 2,"['Pan, Qing', 'Liu, Aijing', 'Zhang, Faming', 'Ling, Yong', 'Ou, Changbo', 'Hou, Na', 'He, Cheng']",BMC Vet Res,,,True
4e9aa1aef7efca6b41b1503135145e0dd75a39ce,PMC,Evolution of vertebrate interferon inducible transmembrane proteins,http://dx.doi.org/10.1186/1471-2164-13-155,PMC3424830,22537233,CC BY,"BACKGROUND: Interferon inducible transmembrane proteins (IFITMs) have diverse roles, including the control of cell proliferation, promotion of homotypic cell adhesion, protection against viral infection, promotion of bone matrix maturation and mineralisation, and mediating germ cell development. Most IFITMs have been well characterised in human and mouse but little published data exists for other animals. This study characterised IFITMs in two distantly related marsupial species, the Australian tammar wallaby and the South American grey short-tailed opossum, and analysed the phylogeny of the IFITM family in vertebrates. RESULTS: Five IFITM paralogues were identified in both the tammar and opossum. As in eutherians, most marsupial IFITM genes exist within a cluster, contain two exons and encode proteins with two transmembrane domains. Only two IFITM genes, IFITM5 and IFITM10, have orthologues in both marsupials and eutherians. IFITM5 arose in bony fish and IFITM10 in tetrapods. The bone-specific expression of IFITM5 appears to be restricted to therian mammals, suggesting that its specialised role in bone production is a recent adaptation specific to mammals. IFITM10 is the most highly conserved IFITM, sharing at least 85% amino acid identity between birds, reptiles and mammals and suggesting an important role for this presently uncharacterised protein. CONCLUSIONS: Like eutherians, marsupials also have multiple IFITM genes that exist in a gene cluster. The differing expression patterns for many of the paralogues, together with poor sequence conservation between species, suggests that IFITM genes have acquired many different roles during vertebrate evolution.",2012 Apr 26,"['Hickford, Danielle', 'Frankenberg, Stephen', 'Shaw, Geoff', 'Renfree, Marilyn B']",BMC Genomics,,,True
bc6cf0a4651155d6bbfc135d42d510b900b3d975,PMC,Evolution of vertebrate interferon inducible transmembrane proteins,http://dx.doi.org/10.1186/1471-2164-13-155,PMC3424830,22537233,CC BY,"BACKGROUND: Interferon inducible transmembrane proteins (IFITMs) have diverse roles, including the control of cell proliferation, promotion of homotypic cell adhesion, protection against viral infection, promotion of bone matrix maturation and mineralisation, and mediating germ cell development. Most IFITMs have been well characterised in human and mouse but little published data exists for other animals. This study characterised IFITMs in two distantly related marsupial species, the Australian tammar wallaby and the South American grey short-tailed opossum, and analysed the phylogeny of the IFITM family in vertebrates. RESULTS: Five IFITM paralogues were identified in both the tammar and opossum. As in eutherians, most marsupial IFITM genes exist within a cluster, contain two exons and encode proteins with two transmembrane domains. Only two IFITM genes, IFITM5 and IFITM10, have orthologues in both marsupials and eutherians. IFITM5 arose in bony fish and IFITM10 in tetrapods. The bone-specific expression of IFITM5 appears to be restricted to therian mammals, suggesting that its specialised role in bone production is a recent adaptation specific to mammals. IFITM10 is the most highly conserved IFITM, sharing at least 85% amino acid identity between birds, reptiles and mammals and suggesting an important role for this presently uncharacterised protein. CONCLUSIONS: Like eutherians, marsupials also have multiple IFITM genes that exist in a gene cluster. The differing expression patterns for many of the paralogues, together with poor sequence conservation between species, suggests that IFITM genes have acquired many different roles during vertebrate evolution.",2012 Apr 26,"['Hickford, Danielle', 'Frankenberg, Stephen', 'Shaw, Geoff', 'Renfree, Marilyn B']",BMC Genomics,,,False
1da81f5357aef31dd451b4ed90e7fb255c9af8ee,PMC,Operational efficiency and sustainability of vector control of malaria and dengue: descriptive case studies from the Philippines,http://dx.doi.org/10.1186/1475-2875-11-269,PMC3425236,22873707,CC BY,"BACKGROUND: Analysis is lacking on the management of vector control systems in disease-endemic countries with respect to the efficiency and sustainability of operations. METHODS: Three locations were selected, at the scale of province, municipality and barangay (i.e. village). Data on disease incidence, programme activities, and programme management were collected on-site through meetings and focus group discussions. RESULTS: Adaptation of disease control strategies to the epidemiological situation per barangay, through micro-stratification, brings gains in efficiency, but should be accompanied by further capacity building on local situational analysis for better selection and targeting of vector control interventions within the barangay. An integrated approach to vector control, aiming to improve the rational use of resources, was evident with a multi-disease strategy for detection and response, and by the use of combinations of vector control methods. Collaboration within the health sector was apparent from the involvement of barangay health workers, re-orientation of job descriptions and the creation of a disease surveillance unit. The engagement of barangay leaders and use of existing community structures helped mobilize local resources and voluntary services for vector control. In one location, local authorities and the community were involved in the planning, implementation and evaluation of malaria control, which triggered local programme ownership. CONCLUSIONS: Strategies that contributed to an improved efficiency and sustainability of vector control operations were: micro-stratification, integration of vector control within the health sector, a multi-disease approach, involvement of local authorities, and empowerment of communities. Capacity building on situational analysis and vector surveillance should be addressed through national policy and guidelines.",2012 Aug 8,"['van den Berg, Henk', 'Velayudhan, Raman', 'Ebol, Antonietta', 'Catbagan, Ben HG', 'Turingan, Romulo', 'Tuso, Marisol', 'Hii, Jeffrey']",Malar J,,,True
d92b7e913f313face4f704f326d15fca9a91183d,PMC,Dengue Virus Serotype 2 Blocks Extracellular Signal-Regulated Kinase and Nuclear Factor-κB Activation to Downregulate Cytokine Production,http://dx.doi.org/10.1371/journal.pone.0041635,PMC3425550,22927911,CC BY,"BACKGROUND: Dengue virus (DENV) infection is the most common mosquito-borne viral disease threatening human health around the world. Type I interferon (IFN) and cytokine production are crucial in the innate immune system. We previously reported that DENV serotype 2 (DENV-2) induced low levels of interferon regulatory factor 3 and NF-κB activation, thus leading to reduced production of IFN-β in the early phase of infection. Here, we determined whether DENV infection not only hampers type I IFN activation but also cytokine production triggered by Toll-like receptor (TLR) signaling. METHODOLOGY/PRINCIPAL FINDINGS: We used quantitative RT-PCR and found that only low levels of IFN-β and inflammatory cytokines such as interleukin 10 (IL-10), IL-12 and tumor necrosis factor α (TNFα) mRNA were detected in DENV-2–infected bone-marrow–derived dendritic cells. Furthermore, DENV-2 infection repressed cytokine production triggered by TLR signaling. To elucidate the molecular mechanisms underlying this suppression event, we measured NF-κB activation by p65 nuclear translocation and luciferase reporter assay and found that NF-κB activation triggered by TLR ligands was blocked by DENV-2 infection. As well, extracellular signal-regulated kinase (ERK) activity was suppressed by DENV-2 infection. CONCLUSIONS/SIGNIFICANCE: To downregulate the host innate immunity, DENV-2 by itself is a weak inducer of type I IFN and cytokines, furthermore DENV-2 can also block the TLR-triggered ERK–NF-κB activation and cytokine production.",2012 Aug 22,"['Chang, Tsung-Hsien', 'Chen, Siang-Ru', 'Yu, Chia-Yi', 'Lin, You-Sheng', 'Chen, Yao-Shen', 'Kubota, Toru', 'Matsuoka, Mayumi', 'Lin, Yi-Ling']",PLoS One,,,True
46ad7c3b64488b2ccb6556e31bc12a5ec9e8de0e,PMC,Identification of a Novel Bat Papillomavirus by Metagenomics,http://dx.doi.org/10.1371/journal.pone.0043986,PMC3427170,22937142,CC BY,"The discovery of novel viruses in animals expands our knowledge of viral diversity and potentially emerging zoonoses. High-throughput sequencing (HTS) technology gives millions or even billions of sequence reads per run, allowing a comprehensive survey of the genetic content within a sample without prior nucleic acid amplification. In this study, we screened 156 rectal swab samples from apparently healthy bats (n = 96), pigs (n = 9), cattles (n = 9), stray dogs (n = 11), stray cats (n = 11) and monkeys (n = 20) using a HTS metagenomics approach. The complete genome of a novel papillomavirus (PV), Miniopterus schreibersii papillomavirus type 1 (MscPV1), with L1 of 60% nucleotide identity to Canine papillomavirus (CPV6), was identified in a specimen from a Common Bent-wing Bat (M. schreibersii). It is about 7.5kb in length, with a G+C content of 45.8% and a genomic organization similar to that of other PVs. Despite the higher nucleotide identity between the genomes of MscPV1 and CPV6, maximum-likelihood phylogenetic analysis of the L1 gene sequence showed that MscPV1 and Erethizon dorsatum papillomavirus (EdPV1) are most closely related. Estimated divergence time of MscPV1 from the EdPV1/MscPV1 common ancestor was approximately 60.2–91.9 millions of years ago, inferred under strict clocks using the L1 and E1 genes. The estimates were limited by the lack of reliable calibration points from co-divergence because of possible host shifts. As the nucleotide sequence of this virus only showed limited similarity with that of related animal PVs, the conventional approach of PCR using consensus primers would be unlikely to have detected the novel virus in the sample. Unlike the first bat papillomavirus RaPV1, MscPV1 was found in an asymptomatic bat with no apparent mucosal or skin lesions whereas RaPV1 was detected in the basosquamous carcinoma of a fruit bat Rousettus aegyptiacus. We propose MscPV1 as the first member of the novel Dyolambda-papillomavirus genus.",2012 Aug 24,"['Tse, Herman', 'Tsang, Alan K. L.', 'Tsoi, Hoi-Wah', 'Leung, Andy S. P.', 'Ho, Chi-Chun', 'Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Yuen, Kwok-Yung']",PLoS One,,,True
7d6a014c0edde2117d005f3228d2b494084b5e8f,PMC,Human viruses: discovery and emergence,http://dx.doi.org/10.1098/rstb.2011.0354,PMC3427559,22966141,CC BY,"There are 219 virus species that are known to be able to infect humans. The first of these to be discovered was yellow fever virus in 1901, and three to four new species are still being found every year. Extrapolation of the discovery curve suggests that there is still a substantial pool of undiscovered human virus species, although an apparent slow-down in the rate of discovery of species from different families may indicate bounds to the potential range of diversity. More than two-thirds of human viruses can also infect non-human hosts, mainly mammals, and sometimes birds. Many specialist human viruses also have mammalian or avian origins. Indeed, a substantial proportion of mammalian viruses may be capable of crossing the species barrier into humans, although only around half of these are capable of being transmitted by humans and around half again of transmitting well enough to cause major outbreaks. A few possible predictors of species jumps can be identified, including the use of phylogenetically conserved cell receptors. It seems almost inevitable that new human viruses will continue to emerge, mainly from other mammals and birds, for the foreseeable future. For this reason, an effective global surveillance system for novel viruses is needed.",2012 Oct 19,"['Woolhouse, Mark', 'Scott, Fiona', 'Hudson, Zoe', 'Howey, Richard', 'Chase-Topping, Margo']",Philos Trans R Soc Lond B Biol Sci,,,True
59532e3fbb23c6bca0ad86898cdf50817b38633f,PMC,Bringing together emerging and endemic zoonoses surveillance: shared challenges and a common solution,http://dx.doi.org/10.1098/rstb.2011.0362,PMC3427560,22966142,CC BY,"Early detection of disease outbreaks in human and animal populations is crucial to the effective surveillance of emerging infectious diseases. However, there are marked geographical disparities in capacity for early detection of outbreaks, which limit the effectiveness of global surveillance strategies. Linking surveillance approaches for emerging and neglected endemic zoonoses, with a renewed focus on existing disease problems in developing countries, has the potential to overcome several limitations and to achieve additional health benefits. Poor reporting is a major constraint to the surveillance of both emerging and endemic zoonoses, and several important barriers to reporting can be identified: (i) a lack of tangible benefits when reports are made; (ii) a lack of capacity to enforce regulations; (iii) poor communication among communities, institutions and sectors; and (iv) complexities of the international regulatory environment. Redirecting surveillance efforts to focus on endemic zoonoses in developing countries offers a pragmatic approach that overcomes some of these barriers and provides support in regions where surveillance capacity is currently weakest. In addition, this approach addresses immediate health and development problems, and provides an equitable and sustainable mechanism for building the culture of surveillance and the core capacities that are needed for all zoonotic pathogens, including emerging disease threats.",2012 Oct 19,"['Halliday, Jo', 'Daborn, Chris', 'Auty, Harriet', 'Mtema, Zacharia', 'Lembo, Tiziana', 'Bronsvoort, Barend M. deC.', 'Handel, Ian', 'Knobel, Darryn', 'Hampson, Katie', 'Cleaveland, Sarah']",Philos Trans R Soc Lond B Biol Sci,,,True
57a9bfeac00b440a156ffa1f6ae21aca7152b22c,PMC,A framework for the study of zoonotic disease emergence and its drivers: spillover of bat pathogens as a case study,http://dx.doi.org/10.1098/rstb.2012.0228,PMC3427567,22966143,CC BY,"Many serious emerging zoonotic infections have recently arisen from bats, including Ebola, Marburg, SARS-coronavirus, Hendra, Nipah, and a number of rabies and rabies-related viruses, consistent with the overall observation that wildlife are an important source of emerging zoonoses for the human population. Mechanisms underlying the recognized association between ecosystem health and human health remain poorly understood and responding appropriately to the ecological, social and economic conditions that facilitate disease emergence and transmission represents a substantial societal challenge. In the context of disease emergence from wildlife, wildlife and habitat should be conserved, which in turn will preserve vital ecosystem structure and function, which has broader implications for human wellbeing and environmental sustainability, while simultaneously minimizing the spillover of pathogens from wild animals into human beings. In this review, we propose a novel framework for the holistic and interdisciplinary investigation of zoonotic disease emergence and its drivers, using the spillover of bat pathogens as a case study. This study has been developed to gain a detailed interdisciplinary understanding, and it combines cutting-edge perspectives from both natural and social sciences, linked to policy impacts on public health, land use and conservation.",2012 Oct 19,"['Wood, James L. N.', 'Leach, Melissa', 'Waldman, Linda', 'MacGregor, Hayley', 'Fooks, Anthony R.', 'Jones, Kate E.', 'Restif, Olivier', 'Dechmann, Dina', 'Hayman, David T. S.', 'Baker, Kate S.', 'Peel, Alison J.', 'Kamins, Alexandra O.', 'Fahr, Jakob', 'Ntiamoa-Baidu, Yaa', 'Suu-Ire, Richard', 'Breiman, Robert F.', 'Epstein, Jonathan H.', 'Field, Hume E.', 'Cunningham, Andrew A.']",Philos Trans R Soc Lond B Biol Sci,,,True
65438bb97d2ff9725a706241b92f3be6f695f368,PMC,"High Influenza A Virus Infection Rates in Mallards Bred for Hunting in the Camargue, South of France",http://dx.doi.org/10.1371/journal.pone.0043974,PMC3428329,22952832,CC BY,"During the last decade, the role of wildlife in emerging pathogen transmission to domestic animals has often been pointed out. Conversely, far less attention has been paid to pathogen transmission from domestic animals to wildlife. Here, we focus on the case of game restocking, which implies the release of millions of animals worldwide each year. We conducted a 2-year study in the Camargue (Southern France) to investigate the influence of hand-reared Mallard releases on avian influenza virus dynamics in surrounding wildlife. We sampled Mallards (cloacal swabs) from several game duck facilities in 2009 and 2010 before their release. A very high (99%) infection rate caused by an H10N7 strain was detected in the game bird facility we sampled in 2009. We did not detect this strain in shot ducks we sampled, neither during the 2008/2009 nor the 2009/2010 hunting seasons. In 2010 infection rates ranged from 0 to 24% in hand-reared ducks. The 2009 H10N7 strain was fully sequenced. It results from multiple reassortment events between Eurasian low pathogenic strains. Interestingly, H10N7 strains had previously caused human infections in Egypt and Australia. The H10 and N7 segments we sequenced were clearly distinct from the Australian ones but they belonged to the same large cluster as the Egyptian ones. We did not observe any mutation linked to increased virulence, transmission to mammals, or antiviral resistance in the H10N7 strain we identified. Our results indicate that the potential role of hand-reared Mallards in influenza virus epizootics must be taken into account given the likely risk of viral exchange between game bird facilities and wild habitats, owing to duck rearing conditions. Measures implemented to limit transmission from wildlife to domestic animals as well as measures to control transmission from domestic animals to wild ones need to be equally reinforced.",2012 Aug 27,"['Vittecoq, Marion', 'Grandhomme, Viviane', 'Champagnon, Jocelyn', 'Guillemain, Matthieu', 'Crescenzo-Chaigne, Bernadette', 'Renaud, François', 'Thomas, Frédéric', 'Gauthier-Clerc, Michel', 'van der Werf, Sylvie']",PLoS One,,,True
e178386cc3ca613c695540267c215754c02f2abe,PMC,Structural Basis for the dsRNA Specificity of the Lassa Virus NP Exonuclease,http://dx.doi.org/10.1371/journal.pone.0044211,PMC3429428,22937163,CC BY,"Lassa virus causes hemorrhagic fever characterized by immunosuppression. The nucleoprotein of Lassa virus, termed NP, binds the viral genome. It also has an additional enzymatic activity as an exonuclease that specifically digests double-stranded RNA (dsRNA). dsRNA is a strong signal to the innate immune system of viral infection. Digestion of dsRNA by the NP exonuclease activity appears to cause suppression of innate immune signaling in the infected cell. Although the fold of the NP enzyme is conserved and the active site completely conserved with other exonucleases in its DEDDh family, NP is atypical among exonucleases in its preference for dsRNA and its strict specificity for one substrate. Here, we present the crystal structure of Lassa virus NP in complex with dsRNA. We find that unlike the exonuclease in Klenow fragment, the double-stranded nucleic acid in complex with Lassa NP remains base-paired instead of splitting, and that binding of the paired complementary strand is achieved by “relocation” of a basic loop motif from its typical exonuclease position. Further, we find that just one single glycine that contacts the substrate strand and one single tyrosine that stacks with a base of the complementary, non-substrate strand are responsible for the unique substrate specificity. This work thus provides templates for development of antiviral drugs that would be specific for viral, rather than host exonucleases of similar fold and active site, and illustrates how a very few amino acid changes confer alternate specificity and biological phenotype to an enzyme.",2012 Aug 28,"['Hastie, Kathryn M.', 'King, Liam B.', 'Zandonatti, Michelle A.', 'Saphire, Erica Ollmann']",PLoS One,,,True
9ce08e8f877a798f4ff11d70112b69f92fc2427f,PMC,"Human Parainfluenza Virus-Associated Respiratory Tract Infection among Children and Genetic Analysis of HPIV-3 Strains in Beijing, China",http://dx.doi.org/10.1371/journal.pone.0043893,PMC3429441,22937119,CC BY,"The relevance of human parainfluenza viruses (HPIVs) to the epidemiology of acute respiratory infections (ARI) in China is unclear. From May 2008 to September 2010, 443 nasopharyngeal aspirates (NPAs) from hospitalized pediatric patients (age from 1 to 93 months) in Beijing were collected and screened for HPIVs and other common respiratory viruses by real-time RT-PCR. Sixty-two of 443 samples were positive for HPIVs with 4 positive for HPIV-2 and 58 positive for HPIV-3, indicating that HPIV-3 was the predominant virus present during the study period. A phylogenetic tree based on all the available HN (hemagglutinin-neuraminidase) sequences of HPIV-3 indicated that three distinct clusters (A,B, and C) were circulating with some temporal and regional clustering. Cluster C was further divided into sub-clusters, C1, C2, C3 and C4. HPIV-3 from Beijing isolates belonged to sub-cluster C3, and were grouped with the isolates from two Provinces of China and the neighboring country of Japan. Genetic analysis based on entire HN gene revealed that the HPIV-3 isolates from Beijing were highly similar with 97.2%–100% identity at the nucleotide level and these could be divided into two closely related lineages, C3a and C3b. These findings suggested that there was co-circulation of multiple lineages of HPIV-3 in the Beijing region during the study period. This is the first study to describe the epidemiology and molecular characterization of HPIVs in China.",2012 Aug 28,"['Mao, Naiying', 'Ji, Yixin', 'Xie, Zhengde', 'Wang, Huanhuan', 'Wang, Huiling', 'An, Junjing', 'Zhang, Xinxin', 'Zhang, Yan', 'Zhu, Zhen', 'Cui, Aili', 'Xu, Songtao', 'Shen, Kunling', 'Liu, Chunyan', 'Yang, Weizhong', 'Xu, Wenbo']",PLoS One,,,True
c146ea9fadc16cfc9571f748391f3aa07f5acbd7,PMC,Genetic Variation and Population Differentiation in a Medical Herb Houttuynia cordata in China Revealed by Inter-Simple Sequence Repeats (ISSRs),http://dx.doi.org/10.3390/ijms13078159,PMC3430227,22942696,CC BY,"Houttuynia cordata is an important traditional Chinese herb with unresolved genetics and taxonomy, which lead to potential problems in the conservation and utilization of the resource. Inter-simple sequence repeat (ISSR) markers were used to assess the level and distribution of genetic diversity in 226 individuals from 15 populations of H. cordata in China. ISSR analysis revealed low genetic variations within populations but high genetic differentiations among populations. This genetic structure probably mainly reflects the historical association among populations. Genetic cluster analysis showed that the basal clade is composed of populations from Southwest China, and the other populations have continuous and eastward distributions. The structure of genetic diversity in H. cordata demonstrated that this species might have survived in Southwest China during the glacial age, and subsequently experienced an eastern postglacial expansion. Based on the results of genetic analysis, it was proposed that as many as possible targeted populations for conservation be included.",2012 Jul 2,"['Wei, Lin', 'Wu, Xian-Jin']",Int J Mol Sci,,,True
92e99304d6df52227598a5da5996127ee119f6fa,PMC,Quantitative and Chemical Fingerprint Analysis for the Quality Evaluation of Isatis indigotica based on Ultra-Performance Liquid Chromatography with Photodiode Array Detector Combined with Chemometric Methods,http://dx.doi.org/10.3390/ijms13079035,PMC3430281,22942750,CC BY,"A simple and reliable method of ultra-performance liquid chromatography with photodiode array detector (UPLC-PDA) was developed to control the quality of Radix Isatidis (dried root of Isatis indigotica) for chemical fingerprint analysis and quantitative analysis of eight bioactive constituents, including R,S-goitrin, progoitrin, epiprogoitrin, gluconapin, adenosine, uridine, guanosine, and hypoxanthine. In quantitative analysis, the eight components showed good regression (R > 0.9997) within test ranges, and the recovery method ranged from 99.5% to 103.0%. The UPLC fingerprints of the Radix Isatidis samples were compared by performing chemometric procedures, including similarity analysis, hierarchical clustering analysis, and principal component analysis. The chemometric procedures classified Radix Isatidis and its finished products such that all samples could be successfully grouped according to crude herbs, prepared slices, and adulterant Baphicacanthis cusiae Rhizoma et Radix. The combination of quantitative and chromatographic fingerprint analysis can be used for the quality assessment of Radix Isatidis and its finished products.",2012 Jul 20,"['Shi, Yan-Hong', 'Xie, Zhi-Yong', 'Wang, Rui', 'Huang, Shan-Jun', 'Li, Yi-Ming', 'Wang, Zheng-Tao']",Int J Mol Sci,,,True
79fedd132f61a7c76b5e323cffb2af73caf9687c,PMC,Establishment of a Reverse Genetics System for Studying Human Bocavirus in Human Airway Epithelia,http://dx.doi.org/10.1371/journal.ppat.1002899,PMC3431310,22956907,CC BY,"Human bocavirus 1 (HBoV1) has been identified as one of the etiological agents of wheezing in young children with acute respiratory-tract infections. In this study, we have obtained the sequence of a full-length HBoV1 genome (including both termini) using viral DNA extracted from a nasopharyngeal aspirate of an infected patient, cloned the full-length HBoV1 genome, and demonstrated DNA replication, encapsidation of the ssDNA genome, and release of the HBoV1 virions from human embryonic kidney 293 cells. The HBoV1 virions generated from this cell line-based production system exhibits a typical icosahedral structure of approximately 26 nm in diameter, and is capable of productively infecting polarized primary human airway epithelia (HAE) from the apical surface. Infected HAE showed hallmarks of lung airway-tract injury, including disruption of the tight junction barrier, loss of cilia and epithelial cell hypertrophy. Notably, polarized HAE cultured from an immortalized airway epithelial cell line, CuFi-8 (originally derived from a cystic fibrosis patient), also supported productive infection of HBoV1. Thus, we have established a reverse genetics system and generated the first cell line-based culture system for the study of HBoV1 infection, which will significantly advance the study of HBoV1 replication and pathogenesis.",2012 Aug 30,"['Huang, Qinfeng', 'Deng, Xuefeng', 'Yan, Ziying', 'Cheng, Fang', 'Luo, Yong', 'Shen, Weiran', 'Lei-Butters, Diana C. M.', 'Chen, Aaron Yun', 'Li, Yi', 'Tang, Liang', 'Söderlund-Venermo, Maria', 'Engelhardt, John F.', 'Qiu, Jianming']",PLoS Pathog,,,True
7516383abbd16005d507e7fb5bb6766a8b0f5894,PMC,Goal-Oriented Respiratory Management for Critically Ill Patients with Acute Respiratory Distress Syndrome,http://dx.doi.org/10.1155/2012/952168,PMC3432327,22957224,CC BY,"This paper, based on relevant literature articles and the authors' clinical experience, presents a goal-oriented respiratory management for critically ill patients with acute respiratory distress syndrome (ARDS) that can help improve clinicians' ability to care for these patients. Early recognition of ARDS modified risk factors and avoidance of aggravating factors during hospital stay such as nonprotective mechanical ventilation, multiple blood products transfusions, positive fluid balance, ventilator-associated pneumonia, and gastric aspiration can help decrease its incidence. An early extensive clinical, laboratory, and imaging evaluation of “at risk patients” allows a correct diagnosis of ARDS, assessment of comorbidities, and calculation of prognostic indices, so that a careful treatment can be planned. Rapid administration of antibiotics and resuscitative measures in case of sepsis and septic shock associated with protective ventilatory strategies and early short-term paralysis associated with differential ventilatory techniques (recruitment maneuvers with adequate positive end-expiratory pressure titration, prone position, and new extracorporeal membrane oxygenation techniques) in severe ARDS can help improve its prognosis. Revaluation of ARDS patients on the third day of evolution (Sequential Organ Failure Assessment (SOFA), biomarkers and response to infection therapy) allows changes in the initial treatment plans and can help decrease ARDS mortality.",2012 Aug 23,"['Barbas, Carmen Sílvia Valente', 'Matos, Gustavo Faissol Janot', 'Amato, Marcelo Britto Passos', 'Carvalho, Carlos Roberto Ribeiro']",Crit Care Res Pract,,,True
5a63d131a9fdbdb837c56458c72d6e29942c1fb9,PMC,Cytokine Immunopathogenesis of Enterovirus 71 Brain Stem Encephalitis,http://dx.doi.org/10.1155/2012/876241,PMC3432373,22956971,CC BY,"Enterovirus 71 (EV71) is one of the most important causes of herpangina and hand, foot, and mouth disease. It can also cause severe complications of the central nervous system (CNS). Brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. EV71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. Cytokines, as a part of innate immunity, favor the development of antiviral and Th1 immune responses. Cytokines and chemokines play an important role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the systemic inflammatory responses to infection play important, but distinctly different, roles in the pathogenesis of EV71 pulmonary edema. Administration of intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been shown to modulate inflammation, to reduce sympathetic overactivity, and to improve survival in patients with EV71 autonomic nervous system dysregulation and pulmonary edema.",2012 Aug 23,"['Wang, Shih-Min', 'Lei, Huan-Yao', 'Liu, Ching-Chuan']",Clin Dev Immunol,,,True
849541788c0fe480a2fb9e13b20f3937e759b249,PMC,Difficulties in demonstrating long term immunity in FeLV vaccinated cats due to increasing age-related resistance to infection,http://dx.doi.org/10.1186/1746-6148-8-125,PMC3433334,22839692,CC BY,"BACKGROUND: Feline leukaemia virus (FeLV) is a pathogen causing fatal illness in cats worldwide, and as such there is a high demand for products to protect against disease. The duration of immunity provided by an inactivated FeLV vaccine, Versifel FeLV, when administered to cats of the target age was determined. Kittens received two vaccinations when aged 7 to 9 weeks old, and were subsequently challenged up to 36 months later with the FeLV-A Glasgow isolate. RESULTS: In all studies, all of the younger aged control kittens showed persistent FeLV p27 antigenaemia confirming that the challenge virus was severe and efficacious. In contrast, the control cats did not show the required level of persistent antigenaemia, with a maximum of 45% cats affected in the middle duration study and only 10% in the longer study. However, apart from one animal in the short duration study, all of the cats vaccinated with Versifel FeLV were negative for persistent antigenaemia and can be considered treatment successes. CONCLUSION: In conclusion, we have shown that although age-related resistance to infection with a virulent FeLV challenge is evident from as early as 10 months of age, vaccination with Versifel FeLV may aid in the protection of cats from FeLV related disease up to three years after primary vaccination as kittens.",2012 Jul 28,"['Wilson, Stephen', 'Greenslade, Juliet', 'Saunders, Gillian', 'Holcroft, Catherine', 'Bruce, Lynn', 'Scobey, Andy', 'Childers, Tedd', 'Sture, Gordon', 'Thompson, James']",BMC Vet Res,,,True
3fd791accf9347c1e74f871c73b7d19c534059ca,PMC,A seroepidemiologic study of Reston ebolavirus in swine in the Philippines,http://dx.doi.org/10.1186/1746-6148-8-82,PMC3433389,22709971,CC BY,"BACKGROUND: Ebola viruses cause viral hemorrhagic fever in humans and non-human primates and are endemic in Africa. Reston ebolavirus (REBOV) has caused several epizootics in cynomolgus monkeys (Macaca fascicularis) but is not associated with any human disease. In late 2008, REBOV infections were identified in swine for the first time in the Philippines. METHODS: A total of 215 swine sera collected at two REBOV-affected farms in 2008, in Pangasinan and Bulacan, were tested for the presence of REBOV-specific antibodies using multiple serodiagnosis systems. A total of 98 swine sera collected in a non-epizootic region, Tarlac, were also tested to clarify the prevalence of REBOV infection in the general swine population in the Philippines. RESULTS: Some 70 % of swine sera at the affected farms were positive for REBOV antibodies in the multiple serodiagnosis systems. On the other hand, none of the swine sera collected in Tarlac showed positive reactions in any of the diagnosis systems. CONCLUSIONS: The high prevalence of REBOV infection in swine in the affected farms in 2008 suggests that swine is susceptible for REBOV infection. The multiple serological assays used in the study are thought to be useful for future surveillance of REOBV infection in swine in the Philippines.",2012 Jun 18,"['Sayama, Yusuke', 'Demetria, Catalino', 'Saito, Mariko', 'Azul, Rachel R', 'Taniguchi, Satoshi', 'Fukushi, Shuetsu', 'Yoshikawa, Tomoki', 'Iizuka, Itoe', 'Mizutani, Tetsuya', 'Kurane, Ichiro', 'Malbas, Fidelino F', 'Lupisan, Socorro', 'Catbagan, Davinio P', 'Animas, Samuel B', 'Morales, Rieldrin G', 'Lopez, Emelinda L', 'Dazo, Karen Rose C', 'Cruz, Magdalena S', 'Olveda, Remigio', 'Saijo, Masayuki', 'Oshitani, Hitoshi', 'Morikawa, Shigeru']",BMC Vet Res,,,True
99e7ae6647b3aef265d79aa84720e5e5b584118d,PMC,Human Anti-CCR4 Minibody Gene Transfer for the Treatment of Cutaneous T-Cell Lymphoma,http://dx.doi.org/10.1371/journal.pone.0044455,PMC3433438,22973452,CC BY,"BACKGROUND: Although several therapeutic options have become available for patients with Cutaneous T-cell Lymphoma (CTCL), no therapy has been curative. Recent studies have demonstrated that CTCL cells overexpress the CC chemokine receptor 4 (CCR4). METHODOLOGY/PRINCIPAL FINDINGS: In this study, a xenograft model of CTCL was established and a recombinant adeno-associated viral serotype 8 (AAV8) vector expressing a humanized single-chain variable fragment (scFv)-Fc fusion (scFvFc or “minibody”) of anti-CCR4 monoclonal antibody (mAb) h1567 was evaluated for curative treatment. Human CCR4(+) tumor-bearing mice treated once with intravenous infusion of AAV8 virions encoding the h1567 (AAV8-h1567) minibody showed anti-tumor activity in vivo and increased survival. The AAV8-h1567 minibody notably increased the number of tumor-infiltrating Ly-6G(+) FcγRIIIa(CD16A)(+) murine neutrophils in the tumor xenografts over that of AAV8-control minibody treated mice. Furthermore, in CCR4(+) tumor-bearing mice co-treated with AAV8-h1567 minibody and infused with human peripheral blood mononuclear cells (PBMCs), marked tumor infiltration of human CD16A(+) CD56(+) NK cells was observed. The h1567 minibody also induced in vitro ADCC activity through both mouse neutrophils and human NK cells. CONCLUSIONS/SIGNIFICANCE: Overall, our data demonstrate that the in vivo anti-tumor activity of h1567 minibody is mediated, at least in part, through CD16A(+) immune effector cell ADCC mechanisms. These data further demonstrate the utility of the AAV-minibody gene transfer system in the rapid evaluation of candidate anti-tumor mAbs and the potency of h1567 as a potential novel therapy for CTCL.",2012 Sep 4,"['Han, Thomas', 'Abdel-Motal, Ussama M.', 'Chang, De-Kuan', 'Sui, Jianhua', 'Muvaffak, Asli', 'Campbell, James', 'Zhu, Quan', 'Kupper, Thomas S.', 'Marasco, Wayne A.']",PLoS One,,,True
4e86bcd31bd05b5c131e397b7d3a74fe4020bb0b,PMC,The Impact of Infection on Population Health: Results of the Ontario Burden of Infectious Diseases Study,http://dx.doi.org/10.1371/journal.pone.0044103,PMC3433488,22962601,CC BY,"BACKGROUND: Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting. METHODOLOGY/PRINCIPAL FINDINGS: We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005–2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization. CONCLUSIONS/SIGNIFICANCE: Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.",2012 Sep 4,"['Kwong, Jeffrey C.', 'Ratnasingham, Sujitha', 'Campitelli, Michael A.', 'Daneman, Nick', 'Deeks, Shelley L.', 'Manuel, Douglas G.', 'Allen, Vanessa G.', 'Bayoumi, Ahmed M.', 'Fazil, Aamir', 'Fisman, David N.', 'Gershon, Andrea S.', 'Gournis, Effie', 'Heathcote, E. Jenny', 'Jamieson, Frances B.', 'Jha, Prabhat', 'Khan, Kamran M.', 'Majowicz, Shannon E.', 'Mazzulli, Tony', 'McGeer, Allison J.', 'Muller, Matthew P.', 'Raut, Abhishek', 'Rea, Elizabeth', 'Remis, Robert S.', 'Shahin, Rita', 'Wright, Alissa J.', 'Zagorski, Brandon', 'Crowcroft, Natasha S.']",PLoS One,,,True
255e2bd7406726ccde903239d96011c340330634,PMC,"Detection of porcine circovirus genotypes 2a and 2b in aborted foetuses from infected swine herds in the State of São Paulo, Brazil",http://dx.doi.org/10.1186/1751-0147-54-29,PMC3434114,22554105,CC BY,"BACKGROUND: Porcine circovirus type 2 (PCV2) has been associated with several disease complexes, including reproductive failure. The aim of this study was to identify the subtypes of PCV2 that are associated with reproductive failure in pigs from the State of São Paulo, Brazil and to investigate co-infections with other infectious organisms. FINDINGS: Samples of 168 aborted foetuses or mummified foetuses from five farrow-to-finish swine farms known to be infected with PCV2 and located in the State of São Paulo were tested for PCV2 by polymerase chain reaction (PCR). Positive samples were additionally tested for porcine parvovirus (PPV), Leptospira spp. and Brucella spp. by PCR. PCV2 was detected in 18 of the samples (10.7%). PPV, Brucella spp. and Leptospira spp were found in 2, 10 and 0 cases, respectively. Eleven PCV2 strains were sequenced and determined to be either genotype 2a (n = 1) or 2b (n = 10). CONCLUSIONS: The findings indicate that the frequency of PCV2 infections in aborted porcine foetuses from the State of São Paulo is rather low (10.7%) and that co-infection with other pathogens is common and may be involved in PCV2 associated reproductive failure. No repeatable, characteristic amino acid motifs for regions of the PCV2 capsid protein seemed to be associated with abortion in sows.",2012 May 3,"['de Castro, Alessandra MMG', 'Cruz, Taís F', 'Salgado, Vanessa R', 'Kanashiro, Tatiana M', 'Ferrari, Karen L', 'Araujo, João P', 'Brandão, Paulo E', 'Richtzenhain, Leonardo J']",Acta Vet Scand,,,True
bf0e3ed6e8fa4adbfacbf76e9fa2f5aa1ccdef19,PMC,The VNTR Polymorphism of the DC-SIGNR Gene and Susceptibility to HIV-1 Infection: A Meta-Analysis,http://dx.doi.org/10.1371/journal.pone.0042972,PMC3434151,22957026,CC BY,"BACKGROUND: Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin related (DC-SIGNR) can bind to the human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein and is thus important for the host-pathogen interaction in HIV-1 infection. Studies of the association between the variable number tandem repeat (VNTR) polymorphism of the DC-SIGNR gene and HIV-1 susceptibility have produced controversial results. METHODS AND FINDINGS: We conducted a meta-analysis of the data contained in the literature to clarify these findings. In total, 10 studies consisting of 2683 HIV-1 patients and 3263 controls (2130 healthy controls and 1133 HIV-1 exposed but seronegative (HESN) controls) were included. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were assessed in the main analyses. Further stratified analyses by ethnicity and sample size were performed. By dividing the controls into two groups, healthy controls and HIV-1 exposed but seronegative (HESN) controls, we explored different genetic models to detect any association between the VNTR polymorphism and predisposition to HIV-1 infection. The results showed that the 5-repeat allele carriers (OR = 0.84, 95% CI = 0.73–0.96) and the 5/5 homozygous (OR = 0.68, 95% CI = 0.50–0.93) had significantly reduced risk when using the HIV-1 exposed but seronegative (HESN) as controls. The stratified analyses by ethnicity and sample size confirmed these findings. However, a low to moderate degree of heterogeneity was also found across studies. CONCLUSIONS: Our findings demonstrate that the VNTR polymorphism of the DC-SIGNR gene is associated with a moderate effect on host susceptibility to HIV-1 infection. Similar to the 32-bp deletion in the chemokine receptor-5 gene (CCR5Δ32), the DC-SIGNR VNTR 5-repeat allele might have a role in resistance to HIV infection, particularly in Asian populations.",2012 Sep 5,"['Li, Hui', 'Yu, Xiao-Min', 'Wang, Jia-Xin', 'Hong, Ze-Hui', 'Tang, Nelson Leung-Sang']",PLoS One,,,True
8c701ddbdb052d08eabd99191bd51916a2656ef4,PMC,Self-Reported Use of Personal Protective Equipment among Chinese Critical Care Clinicians during 2009 H1N1 Influenza Pandemic,http://dx.doi.org/10.1371/journal.pone.0044723,PMC3434157,22957101,CC BY,"BACKGROUND: Critically ill patients with 2009 H1N1 influenza are often treated in intensive care units (ICUs), representing significant risk of nosocomial transmission to critical care clinicians and other patients. Despite a large body of literature and guidelines recommending infection control practices, numerous barriers have been identified in ICUs, leading to poor compliance to the use of personal protective equipment (PPE). The use of PPE among critical care clinicians has not been extensively evaluated, especially during the pandemic influenza. This study examined the knowledge, attitudes, and self-reported behaviors, and barriers to compliance with the use of PPE among ICU healthcare workers (HCWs) during the pandemic influenza. METHODOLOGY/PRINCIPAL FINDINGS: A survey instrument consisting of 36 questions was developed and mailed to all HCWs in 21 ICUs in 17 provinces in China. A total of 733 physicians, nurses, and other professionals were surveyed, and 650 (88.7%) were included in the analysis. Fifty-six percent of respondents reported having received training program of pandemic influenza before they cared for H1N1 patients, while 77% reported to have adequate knowledge of self and patient protection. Only 18% of respondents were able to correctly identify all components of PPE, and 55% reported high compliance (>80%) with PPE use during patient care. In multivariate analysis, vaccination for 2009 H1N1 influenza, positive attitudes towards PPE use, organizational factors such as availability of PPE in ICU, and patient information of influenza precautions, as well as reprimand for noncompliance by the supervisors were associated with high compliance, whereas negative attitudes towards PPE use and violation of PPE use were independent predictors of low compliance. CONCLUSION/SIGNIFICANCE: Knowledge and self-reported compliance to recommended PPE use among Chinese critical care clinicians is suboptimal. The perceived barriers should be addressed in order to close the significant gap between perception and knowledge or behavior.",2012 Sep 5,"['Hu, Xiaoyun', 'Zhang, Zhidan', 'Li, Na', 'Liu, Dexin', 'Zhang, Li', 'He, Wei', 'Zhang, Wei', 'Li, Yuexia', 'Zhu, Cheng', 'Zhu, Guijun', 'Zhang, Lipeng', 'Xu, Fang', 'Wang, Shouhong', 'Cao, Xiangyuan', 'Zhao, Huiying', 'Li, Qian', 'Zhang, Xijing', 'Lin, Jiandong', 'Zhao, Shuangping', 'Li, Chen', 'Du, Bin', None]",PLoS One,,,True
cecee9224f871415878f3787539095673d50ca8a,PMC,Ifitm3 Limits the Severity of Acute Influenza in Mice,http://dx.doi.org/10.1371/journal.ppat.1002909,PMC3435252,22969429,CC BY,"Interferon-induced transmembrane (IFITM) proteins are a family of viral restriction factors that inhibit the entry processes of several pathogenic viruses, including influenza A virus (IAV), in vitro. Here we report that IAV-infected knockout mice lacking the Ifitm locus on chromosome 7 exhibited accelerated disease progression, greater mortality, and higher pulmonary and systemic viral burdens as compared to wild type controls. We further observed that the phenotype of Ifitm3-specific knockout mice was indistinguishable from that of mice lacking the entire Ifitm locus. Ifitm3 was expressed by IAV target cells including alveolar type II pneumocytes and tracheal/bronchial respiratory epithelial cells. Robust Ifitm3 expression was also observed in several tissues in the absence of infection. Among murine Ifitm promoters, only that of Ifitm3 could be induced by type I and II interferons. Ifitm3 could also be upregulated by the gp130 cytokines IL-6 and oncostatin M on cells expressing appropriate receptors, suggesting that multiple cytokine signals could contribute to Ifitm3 expression in a cell or tissue-specific manner. Collectively, these findings establish a central role for Ifitm3 in limiting acute influenza in vivo, and provide further insight into Ifitm3 expression and regulation.",2012 Sep 6,"['Bailey, Charles C.', 'Huang, I-Chueh', 'Kam, Christina', 'Farzan, Michael']",PLoS Pathog,,,True
2c3faeb0d5d8690917ef67e2f36bb59a93072c7b,PMC,Toll-like receptors are critical for clearance of Brucella and play different roles in development of adaptive immunity following aerosol challenge in mice,http://dx.doi.org/10.3389/fcimb.2012.00115,PMC3435510,22973560,CC BY,"Brucella spp. cause undulant fever in humans and brucellosis in variety of other animals. Both innate and adaptive immunity have been shown to be important in controlling Brucella infection. Toll-like receptors (TLRs) represent a group of pattern recognition receptors (PRRs) that play critical roles in the host innate immune response, as well as development of adaptive immunity. In the current report, we investigated the role of TLR signaling in the clearance of Brucella and development of adaptive immunity in TLR2(−/−), TLR4(−/−), or MyD88(−/−) mice following aerosol exposure to B. melitensis 16 M. Consistent with previous reports, MyD88 is required for efficient clearance of Brucella from all three organs (lung, spleen, and liver). The results reveal Th2-skewed immune responses in TLR2(−/−) mice late in infection and support a TLR2 requirement for efficient clearance of Brucella from the lungs, but not from the spleen or liver. Similarly, TLR4 is required for efficient clearance of Brucella from the lung, but exhibits a minor contribution to clearance from the spleen and no demonstrable contribution to clearance from the liver. Lymphocyte proliferation assays suggest that the TLRs are not involved in the development of cell-mediated memory response to Brucella antigen. Antibody detection reveals that TLR2 and 4 are required to generate early antigen-specific IgG, but not during the late stages of infection. TLR2 and 4 are only transiently required for IgM production and not at all for IgA production. In contrast, MyD88 is essential for antigen specific IgG production late in infection, but is not required for IgM generation over the course of infection. Surprisingly, despite the prominent role for MyD88 in clearance from all tissues, MyD88-knockout mice express significantly higher levels of serum IgA. These results confirm the important role of MyD88 in controlling infection in the spleen while providing evidence of a prominent contribution to protection in other tissues. In addition, although TLR4 and TLR2 contribute little to control of spleen infection, a significant contribution to clearance of lung infection is described.",2012 Sep 7,"['Pei, Jianwu', 'Ding, Xicheng', 'Fan, Yaping', 'Rice-Ficht, Allison', 'Ficht, Thomas A.']",Front Cell Infect Microbiol,,,True
6a1b5c9d6a0e52a6e0c3bdf192b5acb5bc9fed40,PMC,Diagnostic Devices for Isothermal Nucleic Acid Amplification,http://dx.doi.org/10.3390/s120608319,PMC3436031,22969402,CC BY,"Since the development of the polymerase chain reaction (PCR) technique, genomic information has been retrievable from lesser amounts of DNA than previously possible. PCR-based amplifications require high-precision instruments to perform temperature cycling reactions; further, they are cumbersome for routine clinical use. However, the use of isothermal approaches can eliminate many complications associated with thermocycling. The application of diagnostic devices for isothermal DNA amplification has recently been studied extensively. In this paper, we describe the basic concepts of several isothermal amplification approaches and review recent progress in diagnostic device development.",2012 Jun 14,"['Chang, Chia-Chen', 'Chen, Chien-Cheng', 'Wei, Shih-Chung', 'Lu, Hui-Hsin', 'Liang, Yang-Hung', 'Lin, Chii-Wann']",Sensors (Basel),,,True
45670b1f604c315c742a23956615cd8ef7745f3a,PMC,Impact of a hospital-wide hand hygiene promotion strategy on healthcare-associated infections,http://dx.doi.org/10.1186/2047-2994-1-13,PMC3436662,22958911,CC BY,"BACKGROUND: During the Severe Acute Respiratory Syndrome (SARS) outbreak, high compliance in healthcare workers to hand hygiene was primarily driven by fear. However, the post-SARS period confirmed that this practice was not sustainable. At the Singapore General Hospital, a 1,600-bedded acute tertiary care hospital, the hand hygiene program was revised in early 2007 following Singapore's signing of the pledge to the World Health Organization (WHO) ""Clean Care is Safer Care"" program. FINDINGS: A multi-prong approach was used in designing the hand hygiene program. This included system change; training and education; evaluation and feedback; reminders in the workplace; and institutional safety climate. Hand hygiene compliance rate improved from 20% (in January 2007) to 61% (2010). Improvement was also seen annually in the compliance to each of the 5 moments as well as in all staff categories. Healthcare-associated MRSA infections were reduced from 0.6 (2007) to 0.3 (2010) per 1000 patient-days. CONCLUSIONS: Leadership's support of the program evidenced through visible leadership presence, messaging and release of resources is the key factor in helping to make the program a true success. The hospital was recognised as a Global Hand Hygiene Expert Centre in January 2011. The WHO multi-prong interventions work in improving compliance and reducing healthcare associated infections.",2012 Mar 23,"['Ling, Moi Lin', 'How, Kue Bien']",Antimicrob Resist Infect Control,,,True
ac6a39a0545f0b00b01c5e6875632f9c0f8883f9,PMC,Establishment and reinforcement of the national reference centers for human microbiology in Belgium,http://dx.doi.org/10.1186/0778-7367-70-16,PMC3436681,22958353,CC BY,"BACKGROUND: Microbiology reference laboratories are critical in the development of high-quality clinical and public health services. In Belgium, the reference laboratories performed their activities on a voluntary basis and lacked a legal status. METHODS: Pathogens or groups of pathogens necessitating a national reference center (NRC) were prioritized based on diagnostic and epidemiologic relevance. Terms of reference for each of these pathogens were developed. RESULTS: Recently, 40 NRCs for different pathogens or groups of pathogens have been installed in Belgium to fulfill the following core functions: offering reference diagnostics, collecting reference materials, sharing information and scientific advice, participating in national and international networks, collaborating with research workgroups, and contributing to surveillance activities. CONCLUSIONS: These NRCs are important focal points of the national and international network in public health microbiology.",2012 Jun 22,"['Muyldermans, Gaëtan', 'Litzroth, Amber', 'Ducoffre, Geneviève', 'Quoilin, Sophie', None]",Arch Public Health,,,True
0ed0bedd5005e893440208e3a176694c21e29db3,PMC,"High Incidence of Multiple Viral Infections Identified in Upper Respiratory Tract Infected Children under Three Years of Age in Shanghai, China",http://dx.doi.org/10.1371/journal.pone.0044568,PMC3436764,22970251,CC BY,"BACKGROUND: Upper respiratory tract infection (URTI) is a major reason for hospitalization in childhood. More than 80% of URTIs are viral. Etiological diagnosis of URTIs is important to make correct clinical decisions on treatment methods. However, data for viral spectrum of URTIs are very limited in Shanghai children. METHODS: Nasopharyngeal swabs were collected from a group of 164 children aged below 3 years who were hospitalized due to acute respiratory infection from May 2009 to July 2010 in Shanghai. A VRDAL multiplex PCR for 10 common respiratory viruses was performed on collected specimens compared with the Seeplex® RV15 ACE Detection kit for 15 respiratory viruses. RESULTS: Viruses were detected in 84 (51.2%) patients by VRDAL multiplex PCR, and 8 (4.9%) of cases were mixed infections. Using the Seeplex® RV15 ACE Detection kit, viruses were detected in 129 (78.7%) patients, 49 (29.9%) were co-infected cases. Identified viruses included 37 of human rhinovirus (22.6% of cases), 32 of influenza A virus (19.5%), 30 of parainfluenzavirus-2 (18.3%), 23 of parainfluenzavirus-3 (14.0%), 15 of human enterovirus (9.1%), 14 each of parainfluenzavirus-1, respiratory syncytial virus B and adenovirus (8.5%), 8 of coronavirus 229E/NL63 (4.9%), 6 of human bocavirus (3.7%), 5 each of influenza B virus and respiratory syncytial virus A (3.0%), 3 of parainfluenzavirus-4 (1.8%), 2 of coronavirus OC43/HKU1 (1.2%), and 1 human metapneumovirus (0.6%). CONCLUSIONS: A high frequency of respiratory infections (78.7%) and co-infections (29.9%) was detected in children with acute respiratory infection symptoms in Shanghai. The Seeplex® RV15 ACE detection method was found to be a more reliable high throughput tool than VRDAL method to simultaneously detect multiple respiratory viruses.",2012 Sep 7,"['Zhang, Guocui', 'Hu, Yunwen', 'Wang, Hongping', 'Zhang, Lu', 'Bao, Yixi', 'Zhou, Xiaoming']",PLoS One,,,True
80637e7403f730cb2e22a4af53fade48a1e42a87,PMC,The highly conserved 5' untranslated region as an effective target towards the inhibition of Enterovirus 71 replication by unmodified and appropriate 2'-modified siRNAs,http://dx.doi.org/10.1186/1423-0127-19-73,PMC3438048,22889374,CC BY,"BACKGROUND: Enterovirus 71 (EV71) is a highly infectious agent that plays an etiological role in hand, foot, and mouth disease. It is associated with severe neurological complications and has caused significant mortalities in recent large-scale outbreaks. Currently, no effective vaccine or specific clinical therapy is available against EV71. METHODS: Unmodified 21 nucleotide small interfering RNAs (siRNAs) and classic 2(′)-modified (2(′)-O-methylation or 2(′)-fluoro modification) siRNAs were designed to target highly conserved 5(′) untranslated region (UTR) of the EV71 genome and employed as anti-EV71 agents. Real-time TaqMan RT-PCR, western blot analysis and plaque assays were carried out to evaluate specific viral inhibition by the siRNAs. RESULTS: Transfection of rhabdomyosarcoma (RD) cells with siRNAs targeting the EV71 genomic 5(′) UTR significantly delayed and alleviated the cytopathic effects of EV71 infection, increased cell viability in EV71-infected RD cells. The inhibitory effect on EV71 replication was sequence-specific and dosage-dependent, with significant corresponding decreases in viral RNA, VP1 protein and viral titer. Appropriate 2(′)-modified siRNAs exhibited similar RNA interference (RNAi) activity with dramatically increased serum stability in comparison with unmodified counterparts. CONCLUSION: Sequences were identified within the highly conserved 5(′) UTR that can be targeted to effectively inhibit EV71 replication through RNAi strategies. Appropriate 2(′)-modified siRNAs provide a promising approach to optimizing siRNAs to overcome barriers on RNAi-based antiviral therapies for broader administration.",2012 Aug 13,"['Deng, Jun-Xia', 'Nie, Xiao-Jing', 'Lei, Ying-Feng', 'Ma, Chao-Feng', 'Xu, Dong-Liang', 'Li, Biao', 'Xu, Zhi-Kai', 'Zhang, Guo-Cheng']",J Biomed Sci,,,True
b27d654e2342664a7dc5ea9442bde90b11b0cefd,PMC,An evaluation of the inhibitory effects against rotavirus infection of edible plant extracts,http://dx.doi.org/10.1186/1743-422X-9-137,PMC3439294,22834653,CC BY,"BACKGROUND: Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The developments of specific, potent and accessible antiviral treatments that restrain rotavirus infection remain important to control rotavirus disease. METHODS: 150 plant extracts with nutritional applications were screened in vitro on MA-104 cells for their antiviral activity against rhesus rotavirus (RRV). One extract (Aspalathus linearis (Burm.f.) R.Dahlgren) was also tested for its effect on the loss of transepithelial resistance (TER) of Caco-2 cells caused by simian rotavirus (SA-11) infection. RESULTS: Aqueous extracts of Nelumbo nucifera Gaertn. fruit, Urtica dioica L. root, Aspalathus linearis (Burm.f.) R.Dahlgren leaves, Glycyrrhiza glabra L. root and Olea europaea L. leaves were found to have strong significant antiviral activity with a 50% inhibitory concentration (IC50) < 300 μg/ml. The pure compound 18ß-glycyrrhetinic acid from Glycyrrhiza glabra was found to have the strongest antiviral activity (IC50 46 μM), followed by luteolin and vitexin from Aspalathus linearis (IC50 respectively 116 μM and 129 μM) and apigenin-7-O-glucoside from Melissa officinalis (IC50 150 μM). A combination of Glycyrrhiza glabra L. + Nelumbo nucifera Gaertn. and Urtica dioica L. + Nelumbo nucifera Gaertn. showed synergy in their anti-viral activities. Aspalathus linearis (Burm.f.) R.Dahlgren showed no positive effect on the maintenance of the TER. CONCLUSIONS: These results indicate that nutritional intervention with extracts of Nelumbo nucifera Gaertn., Aspalathus linearis (Burm.f.) R.Dahlgren, Urtica dioica L., Glycyrrhiza glabra L. and Olea europaea L. might be useful in the treatment of diarrhea caused by rotavirus infection.",2012 Jul 26,"['Knipping, Karen', 'Garssen, Johan', 'van’t Land, Belinda']",Virol J,,,True
5759e5ac8b1cc3c13ba04aded6e588a059ad92a0,PMC,Aerosolized avian influenza virus by laboratory manipulations,http://dx.doi.org/10.1186/1743-422X-9-146,PMC3439333,22866888,CC BY,"BACKGROUND: Avian H5N1 influenza viruses present a challenge in the laboratory environment, as they are difficult to collect from the air due to their small size and relatively low concentration. In an effort to generate effective methods of H5N1 air removal and ensure the safety of laboratory personnel, this study was designed to investigate the characteristics of aerosolized H5N1 produced by laboratory manipulations during research studies. RESULTS: Normal laboratory procedures used to process the influenza virus were carried out independently and the amount of virus polluting the on-site atmosphere was measured. In particular, zootomy, grinding, centrifugation, pipetting, magnetic stirring, egg inoculation, and experimental zoogenetic infection were performed. In addition, common accidents associated with each process were simulated, including breaking glass containers, syringe injection of influenza virus solution, and rupturing of centrifuge tubes. A micro-cluster sampling ambient air pollution collection device was used to collect air samples. The collected viruses were tested for activity by measuring their ability to induce hemagglutination with chicken red blood cells and to propagate in chicken embryos after direct inoculation, the latter being detected by reverse-transcription PCR and HA test. The results showed that the air samples from the normal centrifugal group and the negative-control group were negative, while all other groups were positive for H5N1. CONCLUSIONS: Our findings suggest that there are numerous sources of aerosols in laboratory operations involving H5N1. Thus, laboratory personnel should be aware of the exposure risk that accompanies routine procedures involved in H5N1 processing and take proactive measures to prevent accidental infection and decrease the risk of virus aerosol leakage beyond the laboratory.",2012 Aug 6,"['Li, Zhiping', 'Li, Jinsong', 'Zhang, Yandong', 'Li, Lin', 'Ma, Limin', 'Li, Dan', 'Gao, Feng', 'Xia, Zhiping']",Virol J,,,True
85c008e20de23c6313b57d7e638a61c3c611d315,PMC,Detection of human coronavirus strain HKU1 in a 2 years old girl with asthma exacerbation caused by acute pharyngitis,http://dx.doi.org/10.1186/1743-422X-9-142,PMC3439358,22873773,CC BY,"Respiratory viral infections can trigger asthma attack which may lead to sever morbidity. In this report, using molecular methods, we show the chronological association between human coronavirus - HKU1 infection and asthma exacerbation in a two years and seven months old asthmatic girl who was not under treatment and was otherwise healthy.",2012 Aug 3,"['Amini, Razieh', 'Jahanshiri, Fatemeh', 'Amini, Yasaman', 'Sekawi, Zamberi', 'Jalilian, Farid Azizi']",Virol J,,,True
d4535a63a31f97c7564ddf87608bc8b116ba0df0,PMC,"Sentinel Surveillance of Influenza-Like Illness in Two Hospitals in Maracay, Venezuela: 2006–2010",http://dx.doi.org/10.1371/journal.pone.0044511,PMC3439372,22984519,CC0,"BACKGROUND: Limited information exists on the epidemiology of acute febrile respiratory illnesses in tropical South American countries such as Venezuela. The objective of the present study was to examine the epidemiology of influenza-like illness (ILI) in two hospitals in Maracay, Venezuela. METHODOLOGY/PRINCIPAL FINDINGS: We performed a prospective surveillance study of persons with ILI who presented for care at two hospitals in Maracay, Venezuela, from October 2006 to December 2010. A respiratory specimen and clinical information were obtained from each participant. Viral isolation and identification with immunofluorescent antibodies and molecular methods were employed to detect respiratory viruses such as adenovirus, influenza A and B, parainfluenza, and respiratory sincytial virus, among others. There were 916 participants in the study (median age: 17 years; range: 1 month – 86 years). Viruses were identified in 143 (15.6%) subjects, and one participant was found to have a co-infection with more than one virus. Influenza viruses, including pandemic H1N1 2009, were the most frequently detected pathogens, accounting for 67.4% (97/144) of the viruses detected. Adenovirus (15/144), parainfluenza virus (13/144), and respiratory syncytial virus (11/144) were also important causes of ILI in this study. Pandemic H1N1 2009 virus became the most commonly isolated influenza virus during its initial appearance in 2009. Two waves of the pandemic were observed: the first which peaked in August 2009 and the second - higher than the preceding - that peaked in October 2009. In 2010, influenza A/H3N2 re-emerged as the most predominant respiratory virus detected. CONCLUSIONS/SIGNIFICANCE: Influenza viruses were the most commonly detected viral organisms among patients with acute febrile respiratory illnesses presenting at two hospitals in Maracay, Venezuela. Pandemic H1N1 2009 influenza virus did not completely replace other circulating influenza viruses during its initial appearance in 2009. Seasonal influenza A/H3N2 was the most common influenza virus in the post-pandemic phase.",2012 Sep 11,"['Comach, Guillermo', 'Teneza-Mora, Nimfa', 'Kochel, Tadeusz J.', 'Espino, Carlos', 'Sierra, Gloria', 'Camacho, Daria E.', 'Laguna-Torres, V. Alberto', 'Garcia, Josefina', 'Chauca, Gloria', 'Gamero, Maria E.', 'Sovero, Merly', 'Bordones, Slave', 'Villalobos, Iris', 'Melchor, Angel', 'Halsey, Eric S.']",PLoS One,,,True
e95f81436f54620002c9fc909ba8ff591006bf27,PMC,"Surveillance and Genome Analysis of Human Bocavirus in Patients with Respiratory Infection in Guangzhou, China",http://dx.doi.org/10.1371/journal.pone.0044876,PMC3439446,22984581,CC BY,"Human bocavirus (HBoV) is a novel parvovirus associated with respiratory tract diseases and gastrointestinal illness in adult and pediatric patients throughout the world. To investigate the epidemiological and genetic variation of HBoV in Guangzhou, South China, we screened 3460 throat swab samples from 1686 children and 1774 adults with acute respiratory infection symptoms for HBoV between March 2010 and February 2011, and analyzed the complete genome sequence of 2 HBoV strains. Specimens were screened for HBoV by real-time PCR and other 6 common respiratory viruses by RT-PCR or PCR. HBoV was detected in 58 (1.68%) out of 3460 samples, mostly from pediatric patients (52/58) and inpatient children (47/58). Six adult patients were detected as HBoV positive and 5 were emergency cases. Of these HBoV positive cases, 19 (32.76%) had co-pathogens including influenza virus (n = 5), RSV (n = 5), parainfluenza (n = 4), adenovirus (n = 1), coronavirus (n = 7). The complete genome sequences of 2 HBoVs strains (Genbank no. JN794565 and JN794566) were analyzed. Phylogenetic analysis showed that the 2 HBoV strains were HBoV1, and were most genetically close to ST2 (GenBank accession number DQ0000496). Recombination analysis confirmed that HBoV strain GZ9081 was an intra–genotype recombinant strain among HBoV1 variants.",2012 Sep 11,"['Xu, Lin', 'He, Xia', 'Zhang, Ding-mei', 'Feng, Fa-shen', 'Wang, Zhu', 'Guan, Lin-lin', 'Wu, Jue-heng', 'Zhou, Rong', 'Zheng, Bo-jian', 'Yuen, Kwok-yung', 'Li, Meng-feng', 'Cao, Kai-yuan']",PLoS One,,,True
5eb90019b82d03c01d91fd62ca9ba89d60814f82,PMC,Intense Co-Circulation of Non-Influenza Respiratory Viruses during the First Wave of Pandemic Influenza pH1N1/2009: A Cohort Study in Reunion Island,http://dx.doi.org/10.1371/journal.pone.0044755,PMC3440351,22984554,CC BY,"OBJECTIVE: The aim of the present study was to weigh up, at the community level, the respective roles played by pandemic Influenza (pH1N1) virus and co-circulating human Non-Influenza Respiratory Viruses (NIRVs) during the first wave of the 2009 pH1N1 pandemic. METHODS: A population-based prospective cohort study was conducted in Reunion Island during the austral winter 2009 (weeks 30–44) that allowed identification of 125 households with at least one member who developed symptoms of Influenza-like illness (ILI). Three consecutive nasal swabs were collected from each household member (443 individuals) on day 0, 3 and 8 post-ILI report and tested for pH1N1 and 15 NIRVs by RT-PCR. RESULTS: Two successive waves of viral infections were identified: a first wave (W33–37) when pH1N1 was dominant and co-circulated with NIRVs, sharply interrupted by a second wave (W38–44), almost exclusively composed of NIRVs, mainly human Rhinoviruses (hRV) and Coronaviruses (hCoV). Data suggest that some interference may occur between NIRVs and pH1N1 when they co-circulate within the same household, where NIRVs were more likely to infect pH1N1 negative individuals than pH1N1 positive peers (relative risk: 3.13, 95% CI: 1.80–5.46, P<0.001). Viral shedding was significantly shorter (P = 0.035) in patients who were co-infected by pH1N1 and NIRV or by two different NIRVs compared to those who were infected with only one virus, whatever this virus was (pH1N1 or NIRVs). Although intense co-circulation of NIRVs (especially hRV) likely brought pH1N1 under the detection threshold, it did not prevent spread of the pandemic Influenza virus within the susceptible population nor induction of an extensive herd immunity to it. CONCLUSION: Our results suggest that NIRV co-infections during Influenza epidemics may act as cofactors that contribute to shape an outbreak and modulate the attack rate. They further warrant broad spectrum studies to fully understand viral epidemics.",2012 Sep 12,"['Pascalis, Hervé', 'Temmam, Sarah', 'Turpin, Magali', 'Rollot, Olivier', 'Flahault, Antoine', 'Carrat, Fabrice', 'de Lamballerie, Xavier', 'Gérardin, Patrick', 'Dellagi, Koussay']",PLoS One,,,True
60643032cb50195802cf9a11f268e7301d4ad61a,PMC,Serum Levels of Gelatinase Associated Lipocalin as Indicator of the Inflammatory Status in Coronary Artery Disease,http://dx.doi.org/10.1155/2012/189797,PMC3440856,22988542,CC BY,"Background. Atherosclerosis is a chronic inflammatory disease and the acute clinical manifestations represent acute on chronic inflammation. Neutrophil gelatinase-associated lipocalin (NGAL) is found in the granules of human neutrophils, with many diverse functions. The aim of this study was to evaluate the hypothesis that levels NGAL in blood may reflect the inflammatory process in various stages of coronary artery disease. Methods. We studied 140 patients, with SA 40, UA 35, NSTEMI 40, and STEMI 25, and 20 healthy controls. Serum NGAL was measured upon admission and before coronary angiography. Results. Significant differences were observed in median serum-NGAL(ng/mL) between patients with SA (79.23 (IQR, 37.50–100.32)), when compared with UA (108.00 (68.34–177.59)), NSTEMI (166.49 (109.24–247.20)), and STEMI (178.63 (111.18–305.92)) patients and controls (50.31 (44.30–69.78)) with significant incremental value from SA to STEMI. We observed a positive and significant correlation between serum-NGAL and hs-CRP (spearman coefficient rho = 0.685, P < 0.0001) as well as with neutrophil counts (r = 0.511, P < 0.0001). Conclusions. In patients with coronary artery disease serum levels of NGAL increase and reflect the degree of inflammatory process. In patients with acute coronary syndromes, serum levels of NGAL have high negative predictive value and reflecting the inflammatory status could show the severity of coronary clinical syndrome.",2012 Sep 4,"['Kafkas, Nikolaos', 'Demponeras, Christos', 'Zoubouloglou, Filitsa', 'Spanou, Loukia', 'Babalis, Dimitrios', 'Makris, Konstantinos']",Int J Inflam,,,True
cd1b2d233dba9a6446e41588ecf62f7030b5c75d,PMC,Receptor Usage and the Pathogenesis in Acute and Chronic Virus Infections,http://dx.doi.org/10.3389/fmicb.2012.00289,PMC3441196,23024639,CC BY,,2012 Aug 8,"['Tsunetsugu-Yokota, Yasuko', 'Terahara, Kazutaka']",Front Microbiol,,,True
6f3c5be389b060803e0eaa4727b6180637168dad,PMC,Activity based protein profiling to detect serine hydrolase alterations in virus infected cells,http://dx.doi.org/10.3389/fmicb.2012.00308,PMC3441198,23024641,CC BY,"Activity-based protein profiling (ABPP) is a newly emerging technique that uses active site-directed probes to monitor the functional status of enzymes. Serine hydrolases are one of the largest families of enzymes in mammals. More than 200 serine hydrolases have been identified, but little is known about their specific roles. Serine hydrolases are involved in a variety of physiological functions, including digestion, immune response, blood coagulation, and reproduction. ABPP has been used recently to investigate host–virus interactions and to understand the molecular pathogenesis of virus infections. Monitoring the altered serine hydrolases during viral infection gives insight into the catalytic activity of these enzymes that will help to identify novel targets for diagnostic and therapeutic application. This review presents the usefulness of ABPP in detecting and analyzing functional annotation of host cell serine hydrolases as a result of host–virus interaction.",2012 Aug 22,"['Shahiduzzaman, Md.', 'Coombs, Kevin M.']",Front Microbiol,,,True
7398c3a708a291677e55854601f643ba41d79916,PMC,Arapan-S: a fast and highly accurate whole-genome assembly software for viruses and small genomes,http://dx.doi.org/10.1186/1756-0500-5-243,PMC3441218,22591859,CC BY,"BACKGROUND: Genome assembly is considered to be a challenging problem in computational biology, and has been studied extensively by many researchers. It is extremely difficult to build a general assembler that is able to reconstruct the original sequence instead of many contigs. However, we believe that creating specific assemblers, for solving specific cases, will be much more fruitful than creating general assemblers. FINDINGS: In this paper, we present Arapan-S, a whole-genome assembly program dedicated to handling small genomes. It provides only one contig (along with the reverse complement of this contig) in many cases. Although genomes consist of a number of segments, the implemented algorithm can detect all the segments, as we demonstrate for Influenza Virus A. The Arapan-S program is based on the de Bruijn graph. We have implemented a very sophisticated and fast method to reconstruct the original sequence and neglect erroneous k-mers. The method explores the graph by using neither the shortest nor the longest path, but rather a specific and reliable path based on the coverage level or k-mers’ lengths. Arapan-S uses short reads, and it was tested on raw data downloaded from the NCBI Trace Archive. CONCLUSIONS: Our findings show that the accuracy of the assembly was very high; the result was checked against the European Bioinformatics Institute (EBI) database using the NCBI BLAST Sequence Similarity Search. The identity and the genome coverage was more than 99%. We also compared the efficiency of Arapan-S with other well-known assemblers. In dealing with small genomes, the accuracy of Arapan-S is significantly higher than the accuracy of other assemblers. The assembly process is very fast and requires only a few seconds. Arapan-S is available for free to the public. The binary files for Arapan-S are available through http://sourceforge.net/projects/dnascissor/files/.",2012 May 16,"['Sahli, Mohammed', 'Shibuya, Tetsuo']",BMC Res Notes,,,True
d94c4d8b7d45f77cb6080edf6beae9d4bfb99fb2,PMC,Temporal Percolation of the Susceptible Network in an Epidemic Spreading,http://dx.doi.org/10.1371/journal.pone.0044188,PMC3441612,23028498,CC BY,"In this work, we study the evolution of the susceptible individuals during the spread of an epidemic modeled by the susceptible-infected-recovered (SIR) process spreading on the top of complex networks. Using an edge-based compartmental approach and percolation tools, we find that a time-dependent quantity [Image: see text], namely, the probability that a given neighbor of a node is susceptible at time [Image: see text], is the control parameter of a node void percolation process involving those nodes on the network not-reached by the disease. We show that there exists a critical time [Image: see text] above which the giant susceptible component is destroyed. As a consequence, in order to preserve a macroscopic connected fraction of the network composed by healthy individuals which guarantee its functionality, any mitigation strategy should be implemented before this critical time [Image: see text]. Our theoretical results are confirmed by extensive simulations of the SIR process.",2012 Sep 13,"['Valdez, Lucas Daniel', 'Macri, Pablo Alejandro', 'Braunstein, Lidia Adriana']",PLoS One,,,True
7a97d30ce4a24ab47740cf3bbddf7cacd554e84d,PMC,Temporal Percolation of the Susceptible Network in an Epidemic Spreading,http://dx.doi.org/10.1371/journal.pone.0044188,PMC3441612,23028498,CC BY,"In this work, we study the evolution of the susceptible individuals during the spread of an epidemic modeled by the susceptible-infected-recovered (SIR) process spreading on the top of complex networks. Using an edge-based compartmental approach and percolation tools, we find that a time-dependent quantity [Image: see text], namely, the probability that a given neighbor of a node is susceptible at time [Image: see text], is the control parameter of a node void percolation process involving those nodes on the network not-reached by the disease. We show that there exists a critical time [Image: see text] above which the giant susceptible component is destroyed. As a consequence, in order to preserve a macroscopic connected fraction of the network composed by healthy individuals which guarantee its functionality, any mitigation strategy should be implemented before this critical time [Image: see text]. Our theoretical results are confirmed by extensive simulations of the SIR process.",2012 Sep 13,"['Valdez, Lucas Daniel', 'Macri, Pablo Alejandro', 'Braunstein, Lidia Adriana']",PLoS One,,,True
a28353cd5af668e408edfbc98b21224f3b04c232,PMC,Temporal patterns of charcoal burning suicides among the working age population in Hong Kong SAR: the influence of economic activity status and sex,http://dx.doi.org/10.1186/1471-2458-12-505,PMC3443008,22770504,CC BY,"BACKGROUND: Charcoal burning in a sealed room has recently emerged as the second most common suicide means in Hong Kong, causing approximately 200 deaths each year. As charcoal burning suicide victims have a unique sociodemographic profile (i.e., predominantly economically active men), they may commit suicide at specific times. However, little is known about the temporal patterns of charcoal burning suicides. METHODS: Suicide data from 2001 to 2008 on victims of usual working age (20–59) were obtained from the registered death files of the Census and Statistics Department of Hong Kong. A total of 1649 cases of charcoal burning suicide were analyzed using a two-step procedure, which first examined the temporal asymmetries in the incidence of suicide, and second investigated whether these asymmetries were influenced by sex and/or economic activity status. Poisson regression analyses were employed to model the monthly and daily patterns of suicide by economic activity status and sex. RESULTS: Our findings revealed pronounced monthly and daily temporal variations in the pattern of charcoal burning suicides in Hong Kong. Consistent with previous findings on overall suicide deaths, there was an overall spring peak in April, and Monday was the common high risk day for all groups. Although sex determined the pattern of variation in charcoal burning suicides, the magnitude of the variation was influenced by the economic activity status of the victims. CONCLUSION: The traditional classification of suicide methods as either violent or nonviolent tends to elide the temporal variations of specific methods. The interaction between sex and economic activity status observed in the present study indicates that sex should be taken into consideration when investigating the influence of economic activity status on temporal variations of suicide. This finding also suggests that suicide prevention efforts should be both time- and subgroup-specific.",2012 Jul 6,"['Law, Chi-kin', 'Leung, Candi MC']",BMC Public Health,,,True
c0f496f49f4b2dea73cf8c184ff21275bf706908,PMC,Porcine reproductive and respiratory syndrome virus nonstructural protein 2 contributes to NF-κB activation,http://dx.doi.org/10.1186/1743-422X-9-83,PMC3443020,22546080,CC BY,"BACKGROUND: Nuclear factor-kappaB (NF-κB) is an inducible transcription factor that plays a key role in inflammation and immune responses, as well as in the regulation of cell proliferation and survival. Previous studies by our group and others have demonstrated that porcine reproductive and respiratory syndrome virus (PRRSV) infection could activate NF-κB in MARC-145 cells and alveolar macrophages. The nucleocapsid (N) protein was identified as an NF-κB activator among the structural proteins encoded by PRRSV; however, it remains unclear whether the nonstructural proteins (Nsps) contribute to NF-κB activation. In this study, we identified which Nsps can activate NF-κB and investigated the potential mechanism(s) by which they act. RESULTS: By screening the individual Nsps of PRRSV strain WUH3, Nsp2 exhibited great potential to activate NF-κB in MARC-145 and HeLa cells. Overexpression of Nsp2 induced IκBα degradation and nuclear translocation of NF-κB. Furthermore, Nsp2 also induced NF-κB-dependent inflammatory factors, including interleukin (IL)-6, IL-8, COX-2, and RANTES. Compared with the Nsp2 of the classical PRRSV strain, the Nsp2 of highly pathogenic PRRSV (HP-PRRSV) strains that possess a 30 amino acid (aa) deletion in Nsp2 displayed greater NF-κB activation. However, the 30-aa deletion was demonstrated to not be associated with NF-κB activation. Further functional domain analyses revealed that the hypervariable region (HV) of Nsp2 was essential for NF-κB activation. CONCLUSIONS: Taken together, these data indicate that PRRSV Nsp2 is a multifunctional protein participating in the modulation of host inflammatory response, which suggests an important role of Nsp2 in pathogenesis and disease outcomes.",2012 Apr 30,"['Fang, Ying', 'Fang, Liurong', 'Wang, Yang', 'Lei, Yingying', 'Luo, Rui', 'Wang, Dang', 'Chen, Huanchun', 'Xiao, Shaobo']",Virol J,,,True
ffbe34e6cdad2e0807c420ddee33b842e38e219d,PMC,A novel hierarchical clustering algorithm for gene sequences,http://dx.doi.org/10.1186/1471-2105-13-174,PMC3443659,22823405,CC BY,"BACKGROUND: Clustering DNA sequences into functional groups is an important problem in bioinformatics. We propose a new alignment-free algorithm, mBKM, based on a new distance measure, DMk, for clustering gene sequences. This method transforms DNA sequences into the feature vectors which contain the occurrence, location and order relation of k-tuples in DNA sequence. Afterwards, a hierarchical procedure is applied to clustering DNA sequences based on the feature vectors. RESULTS: The proposed distance measure and clustering method are evaluated by clustering functionally related genes and by phylogenetic analysis. This method is also compared with BlastClust, CD-HIT-EST and some others. The experimental results show our method is effective in classifying DNA sequences with similar biological characteristics and in discovering the underlying relationship among the sequences. CONCLUSIONS: We introduced a novel clustering algorithm which is based on a new sequence similarity measure. It is effective in classifying DNA sequences with similar biological characteristics and in discovering the relationship among the sequences.",2012 Jul 23,"['Wei, Dan', 'Jiang, Qingshan', 'Wei, Yanjie', 'Wang, Shengrui']",BMC Bioinformatics,,,True
0f7c4b6a69f7c82ec245cf64dada9150d1e4b831,PMC,"Herbal Products: Benefits, Limits, and Applications in Chronic Liver Disease",http://dx.doi.org/10.1155/2012/837939,PMC3443820,22991573,CC BY,"Complementary and alternative medicine soughts and encompasses a wide range of approaches; its use begun in ancient China at the time of Xia dynasty and in India during the Vedic period, but thanks to its long-lasting curative effect, easy availability, natural way of healing, and poor side-effects it is gaining importance throughout the world in clinical practice. We conducted a review describing the effects and the limits of using herbal products in chronic liver disease, focusing our attention on those most known, such as quercetin or curcumin. We tried to describe their pharmacokinetics, biological properties, and their beneficial effects (as antioxidant role) in metabolic, alcoholic, and viral hepatitis (considering that oxidative stress is the common pathway of chronic liver diseases of different etiology). The main limit of applicability of CAM comes from the lacking of randomized, placebo-controlled clinical trials giving a real proof of efficacy of those products, so that anecdotal success and personal experience are frequently the driving force for acceptance of CAM in the population.",2012 Sep 6,"['Del Prete, Anna', 'Scalera, Antonella', 'Iadevaia, Maddalena Diana', 'Miranda, Agnese', 'Zulli, Claudio', 'Gaeta, Laura', 'Tuccillo, Concetta', 'Federico, Alessandro', 'Loguercio, Carmelina']",Evid Based Complement Alternat Med,,,True
474978e3a0f1a8064083d7ae5136b968d10184ab,PMC,Transcriptional Regulation of Flotillins by the Extracellularly Regulated Kinases and Retinoid X Receptor Complexes,http://dx.doi.org/10.1371/journal.pone.0045514,PMC3445523,23029064,CC BY,"Flotillin-1 and flotillin-2 are important regulators of signal transduction pathways such as growth factor signaling. Flotillin expression is increased under pathological conditions such as neurodegenerative disorders and cancer. Despite their importance for signal transduction, very little is known about the transcriptional regulation of flotillins. Here, we analyzed the expression of flotillins at transcriptional level and identified flotillins as downstream targets of the mitogen activated kinases ERK1/2. The promoter activity of flotillins was increased upon growth factor stimulation in a MAPK dependent manner. Overexpression of serum response factor or early growth response gene 1 resulted in increased flotillin mRNA and protein expression. Furthermore, both promoter activity and expression of endogenous flotillins were increased upon treatment with retinoic acid or by overexpression of the retinoid X receptor and its binding partners RARα and PPARγ. Our data indicate that the expression of flotillins, which can be detected in all cultured cells, is fine-tuned in response to various external stimuli. This regulation may be critical for the outcome of signaling cascades in which flotillins are known to be involved.",2012 Sep 18,"['Banning, Antje', 'Ockenga, Wymke', 'Finger, Fabian', 'Siebrasse, Philipp', 'Tikkanen, Ritva']",PLoS One,,,True
b11f198de26a3035fb312becd5eeac9a25d5f2c1,PMC,Performance of VIDISCA-454 in Feces-Suspensions and Serum,http://dx.doi.org/10.3390/v4081328,PMC3446766,23012629,CC BY,"Virus discovery combining sequence unbiased amplification with next generation sequencing is now state-of-the-art. We have previously determined that the performance of the unbiased amplification technique which is operational at our institute, VIDISCA-454, is efficient when respiratory samples are used as input. The performance of the assay is, however, not known for other clinical materials like blood or stool samples. Here, we investigated the sensitivity of VIDISCA-454 with feces-suspensions and serum samples that are positive and that have been quantified for norovirus and human immunodeficiency virus type 1, respectively. The performance of VIDISCA-454 in serum samples was equal to its performance in respiratory material, with an estimated lower threshold of 1,000 viral genome copies. The estimated threshold in feces-suspension is around 200,000 viral genome copies. The decreased sensitivity in feces suspension is mainly due to sequences that share no recognizable identity with known sequences. Most likely these sequences originate from bacteria and phages which are not completely sequenced.",2012 Aug 22,"['de Vries, Michel', 'Oude Munnink, Bas B.', 'Deijs, Martin', 'Canuti, Marta', 'Koekkoek, Sylvie M.', 'Molenkamp, Richard', 'Bakker, Margreet', 'Jurriaans, Suzanne', 'van Schaik, Barbera D. C.', 'Luyf, Angela C.', 'Olabarriaga, Silvia D.', 'van Kampen, Antoine H. C.', 'van der Hoek, Lia']",Viruses,,,True
604397da653890b54d4af23b45adab3365e1f042,PMC,Functional Analysis of Rift Valley Fever Virus NSs Encoding a Partial Truncation,http://dx.doi.org/10.1371/journal.pone.0045730,PMC3446906,23029207,CC BY,"Rift Valley fever virus (RVFV), belongs to genus Phlebovirus of the family Bunyaviridae, causes high rates of abortion and fetal malformation in infected ruminants as well as causing neurological disorders, blindness, or lethal hemorrhagic fever in humans. RVFV is classified as a category A priority pathogen and a select agent in the U.S., and currently there are no therapeutics available for RVF patients. NSs protein, a major virulence factor of RVFV, inhibits host transcription including interferon (IFN)-β mRNA synthesis and promotes degradation of dsRNA-dependent protein kinase (PKR). NSs self-associates at the C-terminus 17 aa., while NSs at aa.210–230 binds to Sin3A-associated protein (SAP30) to inhibit the activation of IFN-β promoter. Thus, we hypothesize that NSs function(s) can be abolished by truncation of specific domains, and co-expression of nonfunctional NSs with intact NSs will result in the attenuation of NSs function by dominant-negative effect. Unexpectedly, we found that RVFV NSs truncated at aa. 6–30, 31–55, 56–80, 81–105, 106–130, 131–155, 156–180, 181–205, 206–230, 231–248 or 249–265 lack functions of IFN–β mRNA synthesis inhibition and degradation of PKR. Truncated NSs were less stable in infected cells, while nuclear localization was inhibited in NSs lacking either of aa.81–105, 106–130, 131–155, 156–180, 181–205, 206–230 or 231–248. Furthermore, none of truncated NSs had exhibited significant dominant-negative functions for NSs-mediated IFN-β suppression or PKR degradation upon co-expression in cells infected with RVFV. We also found that any of truncated NSs except for intact NSs does not interact with RVFV NSs even in the presence of intact C-terminus self-association domain. Our results suggest that conformational integrity of NSs is important for the stability, cellular localization and biological functions of RVFV NSs, and the co-expression of truncated NSs does not exhibit dominant-negative phenotype.",2012 Sep 19,"['Head, Jennifer A.', 'Kalveram, Birte', 'Ikegami, Tetsuro']",PLoS One,,,True
96f1b9981028f5954b8f93c8dec9a69c236c124d,PMC,Clinical Impact of Infection with Pandemic Influenza (H1N1) 2009 Virus in Naïve Nucleus and Multiplier Pig Herds in Norway,http://dx.doi.org/10.1155/2011/163745,PMC3447284,23074653,CC BY,The Norwegian pig population has been free from influenza viruses until 2009. The pandemic influenza outbreak during the autumn 2009 provided an opportunity to study the clinical impact of this infection in an entirely naïve pig population. This paper describes the results of a case-control study on the clinical impact of pandemic influenza (H1N1) 2009 infection in the nucleus and multiplier herds in Norway. The infection spread readily and led to seroconversion of 42% of the Norwegian nucleus and multiplier herds within a year. Positive and negative herds were identified based on surveillance data from the Norwegian Veterinary Institute. Telephone interviews were conducted with pig herd owners or managers between November 2010 and January 2011. Pigs with clinical signs were reported from 40% of the case herds with varying morbidity and duration of respiratory disease and reduced reproductive performance. Clinical signs were reported in all age groups.,2011 Dec 22,"['Grøntvedt, Carl Andreas', 'Er, Chiek', 'Gjerset, Britt', 'Germundsson, Anna', 'Framstad, Tore', 'Brun, Edgar', 'Jørgensen, Anne', 'Lium, Bjørn']",Influenza Res Treat,,,True
60abca9911a64805e51aa8deb70bb238c2f3d414,PMC,Influenza-Associated Mortality in Georgia (2009–2011),http://dx.doi.org/10.1155/2012/480763,PMC3447290,23074667,CC BY,"We analyzed data from NCDCPH Georgia where samples from outpatients with influenza-like illness (ILI) and inpatients with severe acute respiratory syndrome (SARI) are referred for testing on influenza virus using PCR analysis. During 2009-2010 and 2010-2011 influenza pandemics total number of the laboratory-confirmed influenza cases were 1286 with 33 deaths (all of them influenza type A) and 1203 (51.4% type A) with 44 deaths, respectively. At least one underlying medical condition was reported in 70.7% (for pandemic influenza strain) and 96% (for influenza type B) of deaths. Predominating preexisting condition was coronary heart disease.",2012 Aug 15,"['Butsashvili, Maia', 'Kandelaki, George', 'Zakhashvili, Khatuna', 'Machablishvili, Ana', 'Avaliani, Nata']",Influenza Res Treat,,,True
3e8d986f56b6afb805e70236871627835e68372c,PMC,Predictive and Reactive Distribution of Vaccines and Antivirals during Cross-Regional Pandemic Outbreaks,http://dx.doi.org/10.1155/2011/579597,PMC3447295,23074658,CC BY,"As recently pointed out by the Institute of Medicine, the existing pandemic mitigation models lack the dynamic decision support capability. We develop a large-scale simulation-driven optimization model for generating dynamic predictive distribution of vaccines and antivirals over a network of regional pandemic outbreaks. The model incorporates measures of morbidity, mortality, and social distancing, translated into the cost of lost productivity and medical expenses. The performance of the strategy is compared to that of the reactive myopic policy, using a sample outbreak in Fla, USA, with an affected population of over four millions. The comparison is implemented at different levels of vaccine and antiviral availability and administration capacity. Sensitivity analysis is performed to assess the impact of variability of some critical factors on policy performance. The model is intended to support public health policy making for effective distribution of limited mitigation resources.",2011 Jun 5,"['Uribe-Sánchez, Andrés', 'Savachkin, Alex']",Influenza Res Treat,,,True
c66d7cf6243be684d42751e19f4f9c27ca8a1f3b,PMC,A Novel Vaccine Using Nanoparticle Platform to Present Immunogenic M2e against Avian Influenza Infection,http://dx.doi.org/10.1155/2011/126794,PMC3447297,23074652,CC BY,"Using peptide nanoparticle technology, we have designed two novel vaccine constructs representing M2e in monomeric (Mono-M2e) and tetrameric (Tetra-M2e) forms. Groups of specific pathogen free (SPF) chickens were immunized intramuscularly with Mono-M2e or Tetra-M2e with and without an adjuvant. Two weeks after the second boost, chickens were challenged with 107.2 EID50 of H5N2 low pathogenicity avian influenza (LPAI) virus. M2e-specific antibody responses to each of the vaccine constructs were tested by ELISA. Vaccinated chickens exhibited increased M2e-specific IgG responses for each of the constructs as compared to a non-vaccinated group. However, the vaccine construct Tetra-M2e elicited a significantly higher antibody response when it was used with an adjuvant. On the other hand, virus neutralization assays indicated that immune protection is not by way of neutralizing antibodies. The level of protection was evaluated using quantitative real time PCR at 4, 6, and 8 days post-challenge with H5N2 LPAI by measuring virus shedding from trachea and cloaca. The Tetra-M2e with adjuvant offered statistically significant (P < 0.05) protection against subtype H5N2 LPAI by reduction of the AI virus shedding. The results suggest that the self-assembling polypeptide nanoparticle shows promise as a potential platform for a development of a vaccine against AI.",2011 Jan 12,"['Babapoor, Sankhiros', 'Neef, Tobias', 'Mittelholzer, Christian', 'Girshick, Theodore', 'Garmendia, Antonio', 'Shang, Hongwei', 'Khan, Mazhar I.', 'Burkhard, Peter']",Influenza Res Treat,,,True
648e9c790e9707c35271988c3f86aa147a9eda05,PMC,"Efficacy and Safety of CVT-E002, a Proprietary Extract of Panax quinquefolius in the Prevention of Respiratory Infections in Influenza-Vaccinated Community-Dwelling Adults: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Trial",http://dx.doi.org/10.1155/2011/759051,PMC3447298,23074661,CC BY,"CVT-E002 (a proprietary extract) was found to be effective in the prevention of upper respiratory infections (URIs) in healthy adults, and institutionalized and community-dwelling seniors. A multicenter, randomized, double-blind, placebo-controlled trial was carried out to determine effects of CVT-E002 in the prevention of URIs in influenza-vaccinated community-dwelling adults. 783 community-dwelling adults were randomized to receive placebo, 400 mg or 800 mg treatment/d (1 : 1 : 1) for 6 months. Primary analysis on the incidence of laboratory-confirmed-clinical URIs (LCCUs), including influenza A and B, was performed on those receiving at least one dose. Secondary analysis was performed on study completers and included incidence, severity, and duration of URIs meeting a Jackson-based criteria and safety of CVT-E002. The incidence of LCCUs in the ITT group was 5.5%, 5.2%, and 4.6% in the placebo, 400 mg and 800 mg groups, respectively (P = 0.89). Jackson-confirmed URIs were significantly lower in the treated groups (P < 0.04). CVT-E002 supplementation reduced the severity and duration of Jackson-confirmed URIs. The results indicate that CVT-E002 can be safely used by similar groups and may prevent symptoms of URIs; larger sample size is warranted.",2011 Jul 20,"['McElhaney, Janet E.', 'Simor, Andrew E.', 'McNeil, Shelly', 'Predy, Gerald N.']",Influenza Res Treat,,,True
a699cfdfda9ccc5ccb41e946a63113106b39148d,PMC,Factors Associated with Increased Risk Perception of Pandemic Influenza in Australia,http://dx.doi.org/10.1155/2010/947906,PMC3447299,23074650,CC BY,"The aim of this study was to assess factors associated with increased risk perception of pandemic influenza in Australia. The sample consisted of 2081 Australian adults aged 16 years and older who completed a short three item pandemic influenza question module which was incorporated into the NSW Health Adult Population Health Survey during the first quarter of 2007. After adjusting for covariates, multivariate analysis indicated that those living in rural regions were significantly more likely to perceive a high risk that a pandemic influenza would occur, while those with poor self-rated health perceived both a high likelihood of pandemic and high concern that self/family would be directly affected were such an event to occur. Those who spoke a language other than English at home and those on low incomes and younger people (16–24 years) were significantly more likely to have changed the way they lived their lives due to the possibility of pandemic influenza, compared to those who spoke only English at home, middle-high income earners, and older age groups, respectively. This data provides an Australian population baseline against which the risk perceptions of demographic subgroups regarding the current, and potential future pandemics, can be compared and monitored.",2010 Jul 20,"['Jacobs, Jennifer', 'Taylor, Melanie', 'Agho, Kingsley', 'Stevens, Garry', 'Barr, Margo', 'Raphael, Beverley']",Influenza Res Treat,,,True
47939863a50677044e74f69efc9b22a80d37562f,PMC,Blow Flies Were One of the Possible Candidates for Transmission of Highly Pathogenic H5N1 Avian Influenza Virus during the 2004 Outbreaks in Japan,http://dx.doi.org/10.1155/2011/652652,PMC3447300,23074659,CC BY,"The 2003-2004 H5N1 highly pathogenic avian influenza (HPAI) outbreaks in Japan were the first such outbreaks in 79 years in Japan. Epidemic outbreaks have been occurring in Southeast Asia, with the most recent in 2010. Knowledge of the transmission route responsible for the HPAI outbreaks in these countries remains elusive. Our studies strongly suggested that field and laboratory studies focusing on mechanical transmission by blow flies should be considered to control H5N1 avian influenza outbreaks, in particular in epidemic areas, where there are high densities of different fly species throughout the year. In this paper, we review these field and laboratory entomological studies and discuss the possibility of blow flies transmitting H5N1 viruses.",2011 Dec 28,"['Sawabe, Kyoko', 'Hoshino, Keita', 'Isawa, Haruhiko', 'Sasaki, Toshinori', 'Kim, Kyeong Soon', 'Hayashi, Toshihiko', 'Tsuda, Yoshio', 'Kurahashi, Hiromu', 'Kobayashi, Mutsuo']",Influenza Res Treat,,,True
9d0653aa163675efb2e832369ae48761148b43ed,PMC,Experiences after Twenty Months with Pandemic Influenza A (H1N1) 2009 Infection in the Naïve Norwegian Pig Population,http://dx.doi.org/10.1155/2011/206975,PMC3447302,23074654,CC BY,"Pandemic (H1N1) 2009 influenza A virus was detected in Norwegian pigs in October 2009. Until then, Norway was regarded free of swine influenza. Intensified screening revealed 91 positive herds within three months. The virus was rapidly transmitted to the susceptible population, including closed breeding herds with high biosecurity. Humans were important for the introduction as well as spread of the virus to pigs. Mild or no clinical signs were observed in infected pigs. Surveillance of SIV in 2010 revealed that 41% of all the Norwegian pig herds had antibodies to pandemic (H1N1) 2009 virus. Furthermore, this surveillance indicated that pigs born in positive herds after the active phase did not seroconvert, suggesting no ongoing infection in the herds. However, results from surveillance in 2011 show a continuing spread of the infection in many herds, either caused by new introduction or by virus circulation since 2009.",2011 Jan 3,"['Gjerset, B.', 'Er, C.', 'Løtvedt, S.', 'Jørgensen, A.', 'Hungnes, O.', 'Lium, B.', 'Germundsson, A.']",Influenza Res Treat,,,True
85f3c300e460e62364ef4a74fb1289334a5c2317,PMC,Protection conferred by a recombinant Marek’s disease virus that expresses the spike protein from infectious bronchitis virus in specific pathogen-free chicken,http://dx.doi.org/10.1186/1743-422X-9-85,PMC3447679,22559869,CC BY,"BACKGROUND: In many countries, the predominant field isolates of infectious bronchitis virus (IBV) have been classified as QX-like strains since 1996. However, no commercial vaccines that are specific for this type of IBV are currently available. Therefore, there is an urgent need to develop novel vaccines that prevent QX-like IBV infection. RESULTS: A recombinant Marek’s disease virus (MDV), rMDV-S1, that expresses the S1 subunit of the spike (S) protein from the QX-like infectious bronchitis virus (IBV) was constructed by inserting the IBV S1 gene into the genome of the CVI988/Rispens strain of MDV. Specific pathogen-free (SPF) chickens that were vaccinated with rMDV-S1 were protected when challenged with the QX-like IBV. They were observed to have mild clinical signs of disease, a short virus-shedding period and low mortality. Additionally, the rMDV-S1 conferred full protection to chickens against virulent MDV, as did the CVI988/Rispens strain. CONCLUSIONS: Our results demonstrate that rMDV-S1 is an effective and promising recombinant vaccine for the prevention of QX-like IBV infection.",2012 May 4,"['Zhang, Xiaorong', 'Wu, Yantao', 'Huang, Yezhen', 'Liu, Xiufan']",Virol J,,,True
891adb48f822d8e7f4749448ea5e2b4828c9aae5,PMC,"Protective efficacy of a broadly cross-reactive swine influenza DNA vaccine encoding M2e, cytotoxic T lymphocyte epitope and consensus H3 hemagglutinin",http://dx.doi.org/10.1186/1743-422X-9-127,PMC3447699,22738661,CC BY,"BACKGROUND: Pigs have been implicated as mixing reservoir for the generation of new pandemic influenza strains, control of swine influenza has both veterinary and public health significance. Unlike human influenza vaccines, strains used for commercially available swine influenza vaccines are not regularly replaced, making the vaccines provide limited protection against antigenically diverse viruses. It is therefore necessary to develop broadly protective swine influenza vaccines that are efficacious to both homologous and heterologous virus infections. In this study, two forms of DNA vaccines were constructed, one was made by fusing M2e to consensus H3HA (MHa), which represents the majority of the HA sequences of H3N2 swine influenza viruses. Another was made by fusing M2e and a conserved CTL epitope (NP147-155) to consensus H3HA (MNHa). Their protective efficacies against homologous and heterologous challenges were tested. RESULTS: BALB/c mice were immunized twice by particle-mediated epidermal delivery (gene gun) with the two DNA vaccines. It was shown that the two vaccines elicited substantial antibody responses, and MNHa induced more significant T cell-mediated immune response than MHa did. Then two H3N2 strains representative of different evolutional and antigenic clusters were used to challenge the vaccine-immunized mice (homosubtypic challenge). Results indicated that both of the DNA vaccines prevented homosubtypic virus infections completely. The vaccines’ heterologous protective efficacies were further tested by challenging with a H1N1 swine influenza virus and a reassortant 2009 pandemic strain. It was found that MNHa reduced the lung viral titers significantly in both challenge groups, histopathological observation showed obvious reduction of lung pathogenesis as compared to MHa and control groups. CONCLUSIONS: The combined utility of the consensus HA and the conserved M2e and CTL epitope can confer complete and partial protection against homologous and heterologous challenges, respectively, in mouse model. This may provide a basis for the development of universal swine influenza vaccines.",2012 Jun 27,"['Wang, Bin', 'Yu, Hai', 'Yang, Fu-Ru', 'Huang, Meng', 'Ma, Ji-Hong', 'Tong, Guang-Zhi']",Virol J,,,True
8aef75d2d213cab0a2b4661fc9971507863ff9ed,PMC,Use of functional gene arrays for elucidating in situ biodegradation,http://dx.doi.org/10.3389/fmicb.2012.00339,PMC3448134,23049526,CC BY,"Microarrays have revolutionized the study of microbiology by providing a high-throughput method for examining thousands of genes with a single test and overcome the limitations of many culture-independent approaches. Functional gene arrays (FGA) probe a wide range of genes involved in a variety of functions of interest to microbial ecology (e.g., carbon degradation, N fixation, metal resistance) from many different microorganisms, cultured and uncultured. The most comprehensive FGA to date is the GeoChip array, which targets tens of thousands of genes involved in the geochemical cycling of carbon, nitrogen, phosphorus, and sulfur, metal resistance and reduction, energy processing, antibiotic resistance and contaminant degradation as well as phylogenetic information (gyrB). Since the development of GeoChips, many studies have been performed using this FGA and have shown it to be a powerful tool for rapid, sensitive, and specific examination of microbial communities in a high-throughput manner. As such, the GeoChip is well-suited for linking geochemical processes with microbial community function and structure. This technology has been used successfully to examine microbial communities before, during, and after in situ bioremediation at a variety of contaminated sites. These studies have expanded our understanding of biodegradation and bioremediation processes and the associated microorganisms and environmental conditions responsible. This review provides an overview of FGA development with a focus on the GeoChip and highlights specific GeoChip studies involving in situ bioremediation.",2012 Sep 21,"['Nostrand, Joy D. Van', 'He, Zhili', 'Zhou, Jizhong']",Front Microbiol,,,True
72ac928abb4394f723426f2e506d71d4892c1036,PMC,Functional Studies of ssDNA Binding Ability of MarR Family Protein TcaR from Staphylococcus epidermidis,http://dx.doi.org/10.1371/journal.pone.0045665,PMC3448645,23029170,CC BY,"The negative transcription regulator of the ica locus, TcaR, regulates proteins involved in the biosynthesis of poly-N-acetylglucosamine (PNAG). Absence of TcaR increases PNAG production and promotes biofilm formation in Staphylococci. Previously, the 3D structure of TcaR in its apo form and its complex structure with several antibiotics have been analyzed. However, the detailed mechanism of multiple antibiotic resistance regulator (MarR) family proteins such as TcaR is unclear and only restricted on the binding ability of double-strand DNA (dsDNA). Here we show by electrophoretic mobility shift assay (EMSA), electron microscopy (EM), circular dichroism (CD), and Biacore analysis that TcaR can interact strongly with single-stranded DNA (ssDNA), thereby identifying a new role in MarR family proteins. Moreover, we show that TcaR preferentially binds 33-mer ssDNA over double-stranded DNA and inhibits viral ssDNA replication. In contrast, such ssDNA binding properties were not observed for other MarR family protein and TetR family protein, suggesting that the results from our studies are not an artifact due to simple charge interactions between TcaR and ssDNA. Overall, these results suggest a novel role for TcaR in regulation of DNA replication. We anticipate that the results of this work will extend our understanding of MarR family protein and broaden the development of new therapeutic strategies for Staphylococci.",2012 Sep 21,"['Chang, Yu-Ming', 'Chen, Cammy K. -M.', 'Chang, Yuan-Chih', 'Jeng, Wen-Yih', 'Hou, Ming-Hon', 'Wang, Andrew H. -J.']",PLoS One,,,True
2b91f521c12a736203029e85675120740c3c1810,PMC,Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model,http://dx.doi.org/10.1371/journal.pone.0045842,PMC3454321,23029269,CC BY,"In terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology of SARS-coronavirus (SARS-CoV) infection, as well as identify correlates of immunity to help develop vaccines for severe coronaviral infections. Here we use a SARS-CoV infection-reinfection ferret model and a functional genomics approach to gain insight into SARS immunopathogenesis and to identify correlates of immune protection during SARS-CoV-challenge in ferrets previously infected with SARS-CoV or immunized with a SARS virus vaccine. We identified gene expression signatures in the lungs of ferrets associated with primary immune responses to SARS-CoV infection and in ferrets that received an identical second inoculum. Acute SARS-CoV infection prompted coordinated innate immune responses that were dominated by antiviral IFN response gene (IRG) expression. Reinfected ferrets, however, lacked the integrated expression of IRGs that was prevalent during acute infection. The expression of specific IRGs was also absent upon challenge in ferrets immunized with an inactivated, Al(OH)(3)-adjuvanted whole virus SARS vaccine candidate that protected them against SARS-CoV infection in the lungs. Lack of IFN-mediated immune enhancement in infected ferrets that were previously inoculated with, or vaccinated against, SARS-CoV revealed 9 IRG correlates of protective immunity. This data provides insight into the molecular pathogenesis of SARS-CoV and SARS-like-CoV infections and is an important resource for the development of CoV antiviral therapeutics and vaccines.",2012 Sep 24,"['Cameron, Mark J.', 'Kelvin, Alyson A.', 'Leon, Alberto J.', 'Cameron, Cheryl M.', 'Ran, Longsi', 'Xu, Luoling', 'Chu, Yong-Kyu', 'Danesh, Ali', 'Fang, Yuan', 'Li, Qianjun', 'Anderson, Austin', 'Couch, Ronald C.', 'Paquette, Stephane G.', 'Fomukong, Ndingsa G.', 'Kistner, Otfried', 'Lauchart, Manfred', 'Rowe, Thomas', 'Harrod, Kevin S.', 'Jonsson, Colleen B.', 'Kelvin, David J.']",PLoS One,,,True
f763d5c729b3a02773062e212f3f2632d2ebb574,PMC,"Safety and Efficacy Profile of Echinacea purpurea to Prevent Common Cold Episodes: A Randomized, Double-Blind, Placebo-Controlled Trial",http://dx.doi.org/10.1155/2012/841315,PMC3457740,23024696,CC BY,"Objective. To investigate the safety (risk) and efficacy (benefit) of Echinacea purpurea extract in the prevention of common cold episodes in a large population over a 4-month period. Methods. 755 healthy subjects were allocated to receive either an alcohol extract from freshly harvested E. purpurea (95% herba and 5% root) or placebo. Participants were required to record adverse events and to rate cold-related issues in a diary throughout the investigation period. Nasal secretions were sampled at acute colds and screened for viruses. Results. A total of 293 adverse events occurred with Echinacea and 306 with placebo treatment. Nine and 10% of participants experienced adverse events, which were at least possibly related to the study drug (adverse drug reactions). Thus, the safety of Echinacea was noninferior to placebo. Echinacea reduced the total number of cold episodes, cumulated episode days within the group, and pain-killer medicated episodes. Echinacea inhibited virally confirmed colds and especially prevented enveloped virus infections (P < 0.05). Echinacea showed maximal effects on recurrent infections, and preventive effects increased with therapy compliance and adherence to the protocol. Conclusions. Compliant prophylactic intake of E. purpurea over a 4-month period appeared to provide a positive risk to benefit ratio.",2012 Sep 16,"['Jawad, M.', 'Schoop, R.', 'Suter, A.', 'Klein, P.', 'Eccles, R.']",Evid Based Complement Alternat Med,,,True
7a1329845e6f9569ebad76566c23cf88fd8d5508,PMC,The VP3 Factor from Viruses of Birnaviridae Family Suppresses RNA Silencing by Binding Both Long and Small RNA Duplexes,http://dx.doi.org/10.1371/journal.pone.0045957,PMC3458112,23049903,CC BY,"RNA silencing is directly involved in antiviral defense in a wide variety of eukaryotic organisms, including plants, fungi, invertebrates, and presumably vertebrate animals. The study of RNA silencing-mediated antiviral defences in vertebrates is hampered by the overlap with other antiviral mechanisms; thus, heterologous systems are often used to study the interplay between RNA silencing and vertebrate-infecting viruses. In this report we show that the VP3 protein of the avian birnavirus Infectious bursal disease virus (IBDV) displays, in addition to its capacity to bind long double-stranded RNA, the ability to interact with double-stranded small RNA molecules. We also demonstrate that IBDV VP3 prevents the silencing mediated degradation of a reporter mRNA, and that this silencing suppression activity depends on its RNA binding ability. Furthermore, we find that the anti-silencing activity of IBDV VP3 is shared with the homologous proteins expressed by both insect- and fish-infecting birnaviruses. Finally, we show that IBDV VP3 can functionally replace the well-characterized HCPro silencing suppressor of Plum pox virus, a potyvirus that is unable to infect plants in the absence of an active silencing suppressor. Altogether, our results support the idea that VP3 protects the viral genome from host sentinels, including those of the RNA silencing machinery.",2012 Sep 25,"['Valli, Adrian', 'Busnadiego, Idoia', 'Maliogka, Varvara', 'Ferrero, Diego', 'Castón, José R.', 'Rodríguez, José Francisco', 'García, Juan Antonio']",PLoS One,,,True
3ebbe01c6f991fcc45a9b12f9421acd50d756503,PMC,"Surveillance on secular trends of incidence and mortality for device–associated infection in the intensive care unit setting at a tertiary medical center in Taiwan, 2000–2008: A retrospective observational study",http://dx.doi.org/10.1186/1471-2334-12-209,PMC3458996,22963041,CC BY,"BACKGROUND: Device–associated infection (DAI) plays an important part in nosocomial infection. Active surveillance and infection control are needed to disclose the specific situation in each hospital and to cope with this problem effectively. We examined the rates of DAI by antimicrobial-resistant pathogens, and 30–day and in–hospital mortality in the intensive care unit (ICU). METHODS: Prospective surveillance was conducted in a mixed medical and surgical ICU at a major teaching hospital from 2000 through 2008. Trend analysis was performed and logistic regression was used to assess prognostic factors of mortality. RESULTS: The overall rate of DAIs was 3.03 episodes per 1000 device–days. The most common DAI type was catheter–associated urinary tract infection (3.76 per 1000 urinary catheter–days). There was a decrease in DAI rates in 2005 and rates of ventilator–associated pneumonia (VAP, 3.18 per 1000 ventilator–days) have remained low since then (p < 0.001). The crude rates of 30–day (33.6%) and in–hospital (52.3%) mortality, as well as infection by antibiotic-resistant VAP pathogens also decreased. The most common antimicrobial-resistant pathogens were methicillin–resistant Staphylococcus aureus (94.9%) and imipenem–resistant Acinetobacter baumannii (p < 0.001), which also increased at the most rapid rate. The rate of antimicrobial resistance among Enterobacteriaceae also increased significantly (p < 0.05). After controlling for potentially confounding factors, the DAI was an independent prognostic factor for both 30–day mortality (OR 2.51, 95% confidence interval [CI] 1.99–3.17, p = 0.001) and in–hospital mortality (OR 3.61, 95% CI 2.10–3.25, p < 0.001). CONCLUSIONS: The decrease in the rate of DAI and infection by resistant bacteria on the impact of severe acute respiratory syndrome can be attributed to active infection control and improved adherence after 2003.",2012 Sep 10,"['Chen, Yin-Yin', 'Chen, Liang-Yu', 'Lin, Seng-Yi', 'Chou, Pesus', 'Liao, Shu-Yuan', 'Wang, Fu-Der']",BMC Infect Dis,,,True
0f8451b64b7aa2e642036d79efc1969125c45873,PMC,Association between insertion/deletion polymorphism in angiotensin-converting enzyme gene and acute lung injury/acute respiratory distress syndrome: a meta-analysis,http://dx.doi.org/10.1186/1471-2350-13-76,PMC3459791,22938636,CC BY,"BACKGROUND: A previous meta-analysis reported a positive association between an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) and the risk of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Here, we updated this meta-analysis and additionally assessed the association of this polymorphism with ALI/ARDS mortality. METHODS: We searched electronic databases through October 2011 for the terms “angiotensin-converting enzyme gene”, “acute lung injury”, and “acute respiratory distress syndrome,” and reviewed all studies that reported the relationship of the I/D polymorphism in ACE with ALI/ARDS in humans. Seven studies met the inclusion criteria, comprising 532 ALI/ARDS patients, 3032 healthy controls, and 1432 patients without ALI/ARDS. We used three genetic models: the allele, dominant, and recessive models. RESULTS: The ACE I/D polymorphism was not associated with susceptibility to ALI/ARDS for any genetic model. However, the ACE I/D polymorphism was associated with the mortality risk of ALI/ARDS in Asian subjects ( P(allele) < 0.0001, P(dominant) = 0.001, P(recessive) = 0.002). This finding remained significant after correction for multiple comparisons. CONCLUSIONS: There is a possible association between the ACE I/D polymorphism genotype and the mortality risk of ALI/ARDS in Asians.",2012 Aug 31,"['Matsuda, Akihisa', 'Kishi, Taro', 'Jacob, Asha', 'Aziz, Monowar', 'Wang, Ping']",BMC Med Genet,,,True
739e01113e6c837a1fb973b1ab7e434cc9c27904,PMC,"Differential Effects of IL-12 on Tregs and Non-Treg T Cells: Roles of IFN-γ, IL-2 and IL-2R",http://dx.doi.org/10.1371/journal.pone.0046241,PMC3459844,23029447,CC BY,"Complex interactions between effector T cells and Foxp3(+) regulatory T cells (Treg) contribute to clinical outcomes in cancer, and autoimmune and infectious diseases. Previous work showed that IL-12 reversed Treg-mediated suppression of CD4(+)Foxp3(−) T cell (Tconv) proliferation. We and others have also shown that Tregs express T-bet and IFN-γ at sites of Th1 inflammation and that IL-12 induces IFN-γ production by Tregs in vitro. To investigate whether loss of immunosuppression occurs when IFN-γ is expressed by Tregs we treated mouse lymphocyte cultures with IL-12. IFN-γ expression did not decrease the ability of Tregs to suppress Tconv proliferation. Rather, IL-12 treatment decreased Treg frequency and Foxp3 levels in Tregs. We further showed that IL-12 increased IL-2R expression on Tconv and CD8 T cells, diminished its expression on Tregs and decreased IL-2 production by Tconv and CD8 T cells. Together, these IL-12 mediated changes favored the outgrowth of non-Tregs. Additionally, we showed that treatment with a second cytokine, IL-27, decreased IL-2 expression without augmenting Tconv and CD8 T cell proliferation. Notably, IL-27 only slightly modified levels of IL-2R on non-Treg T cells. Together, these results show that IL-12 has multiple effects that modify the balance between Tregs and non-Tregs and support an important role for relative levels of IL-2R but not for IFN-γ expression in IL-12-mediated reversal of Treg immunosuppression.",2012 Sep 27,"['Zhao, Jingxian', 'Zhao, Jincun', 'Perlman, Stanley']",PLoS One,,,True
d077e86d41dd4161565d2edf1446d8bc4ec5ed0a,PMC,"Genetic Variation in the TNF Gene Is Associated with Susceptibility to Severe Sepsis, but Not with Mortality",http://dx.doi.org/10.1371/journal.pone.0046113,PMC3459853,23029405,CC BY,"BACKGROUND: Tumor necrosis factor (TNF) and TNF receptor superfamily (TNFR)-mediated immune response play an essential role in the pathogenesis of severe sepsis. Studies examining associations of TNF and lymphotoxin-α (LTA) single nucleotide polymorphisms (SNPs) with severe sepsis have produced conflicting results. The objective of this study was to investigate whether genetic variation in TNF, LTA, TNFRSF1A and TNFRSF1B was associated with susceptibility to or death from severe sepsis in Chinese Han population. METHODOLOGY/PRINCIPAL FINDINGS: Ten SNPs in TNF, LTA, TNFRSF1A and TNFRSF1B were genotyped in samples of patients with severe sepsis (n = 432), sepsis (n = 384) and healthy controls (n = 624). Our results showed that rs1800629, a SNP in the promoter region of TNF, was significantly associated with risk for severe sepsis. The minor allele frequency of rs1800629 was significantly higher in severe sepsis patients than that in both healthy controls (P(adj) = 0.00046, odds ratio (OR)(adj) = 1.92) and sepsis patients (P(adj) = 0.002, OR(adj) = 1.56). Further, we investigated the correlation between rs1800629 genotypes and TNF-α concentrations in peripheral blood mononuclear cells (PBMCs) of healthy volunteers exposed to lipopolysaccharides (LPS) ex vivo, and the association between rs1800629 and TNF-α serum levels in severe sepsis patients. After exposure to LPS, the TNF-α concentration in culture supernatants of PBMCs was significantly higher in the subjects with AA+AG genotypes than that with GG genotype (P = 0.007). Moreover, in patients with severe sepsis, individuals with AA+AG genotypes had significantly higher TNF-α serum concentrations than those with GG genotype (P(adj) = 0.02). However, there were no significant associations between SNPs in the four candidate genes and 30 day mortality for patients with severe sepsis. CONCLUSIONS/SIGNIFICANCE: Our findings suggested that the functional TNF gene SNP rs1800629 was strongly associated with susceptibility to severe sepsis, but not with lethality in Chinese Han population.",2012 Sep 27,"['Song, Zhenju', 'Song, Yuanlin', 'Yin, Jun', 'Shen, Yao', 'Yao, Chenling', 'Sun, Zhan', 'Jiang, Jinjun', 'Zhu, Duming', 'Zhang, Yong', 'Shen, Qinjun', 'Gao, Lei', 'Tong, Chaoyang', 'Bai, Chunxue']",PLoS One,,,True
a9e209c7a59e188267e27014ed46db5490b57543,PMC,Partial and Full PCR-Based Reverse Genetics Strategy for Influenza Viruses,http://dx.doi.org/10.1371/journal.pone.0046378,PMC3460856,23029501,CC BY,"Since 1999, plasmid-based reverse genetics (RG) systems have revolutionized the way influenza viruses are studied. However, it is not unusual to encounter cloning difficulties for one or more influenza genes while attempting to recover virus de novo. To overcome some of these shortcomings we sought to develop partial or full plasmid-free RG systems. The influenza gene of choice is assembled into a RG competent unit by virtue of overlapping PCR reactions containing a cDNA copy of the viral gene segment under the control of RNA polymerase I promoter (pol1) and termination (t1) signals – herein referred to as Flu PCR amplicons. Transfection of tissue culture cells with either HA or NA Flu PCR amplicons and 7 plasmids encoding the remaining influenza RG units, resulted in efficient virus rescue. Likewise, transfections including both HA and NA Flu PCR amplicons and 6 RG plasmids also resulted in efficient virus rescue. In addition, influenza viruses were recovered from a full set of Flu PCR amplicons without the use of plasmids.",2012 Sep 28,"['Chen, Hongjun', 'Ye, Jianqiang', 'Xu, Kemin', 'Angel, Matthew', 'Shao, Hongxia', 'Ferrero, Andrea', 'Sutton, Troy', 'Perez, Daniel R.']",PLoS One,,,True
a015401a1cdf151bd0bca060bd8eb96d6683a147,PMC,"Identification, Characterization and Application of a G-Quadruplex Structured DNA Aptamer against Cancer Biomarker Protein Anterior Gradient Homolog 2",http://dx.doi.org/10.1371/journal.pone.0046393,PMC3460915,23029506,CC BY,"BACKGROUND: Anterior gradient homolog 2 (AGR2) is a functional protein with critical roles in a diverse range of biological systems, including vertebrate tissue development, inflammatory tissue injury responses, and cancer progression. Clinical studies have shown that the AGR2 protein is overexpressed in a wide range of human cancers, including carcinomas of the esophagus, pancreas, breast, prostate, and lung, making the protein as a potential cancer biomarker. However, the general biochemical functions of AGR2 in human cells remain undefined, and the signaling mechanisms that drive AGR2 to inhibit p53 are still not clearly illustrated. Therefore, it is of great interest to develop molecular probes specifically recognizing AGR2 for its detection and for the elucidation of AGR2-associated molecular mechanism. METHODOLOGY/PRINCIPAL FINDINGS: Through a bead-based and flow cytometry monitored SELEX technology, we have identified a group of DNA aptamers that can specifically bind to AGR2 with K(d) values in the nanomolar range after 14 rounds of selections. Aptamer C14B was chosen to further study, due to its high binding affinity and specificity. The optimized and shortened C14B1 has special G-rich characteristics, and the G-rich region of this binding motif was further characterized to reveal an intramolecular parallel G-quadruplex by CD spectroscopy and UV spectroscopy. Our experiments confirmed that the stability of the G-quadruplex structure was strongly dependent on the nature of the monovalent ions and the formation of G-quadruplex structure was also important for the binding capacity of C14B1 to the target. Furthermore, we have designed a kind of allosteric molecule beacon (aMB) probe for selective and sensitive detection of AGR2. CONCLUSION/SIGNIFICANCE: In this work, we have developed new aptamer probes for specific recognition of the AGR2. Structural study have identified that the binding motif of aptamer is an intramolecular parallel G-quadruplex structure and its structure and binding affinity are strongly dependent on the nature of the monovalent ion. Furthermore, with our design of AGR2-aMB, AGR2 could be sensitively and selectively detected. This aptamer probe has great potential to serve as a useful tool for early diagnosis and prognosis of cancer and for fundamental research to elucidate the biochemical functions of AGR2.",2012 Sep 28,"['Wu, Jie', 'Wang, Chi', 'Li, Xilan', 'Song, Yanling', 'Wang, Wei', 'Li, Cong', 'Hu, Jia', 'Zhu, Zhi', 'Li, Jiuxing', 'Zhang, Weiyun', 'Lu, Zhongxian', 'Yang, Chaoyong James']",PLoS One,,,True
faada181a26e163dce05aa155b1516a66bb6154b,PMC,Airport sentinel surveillance and entry quarantine for dengue infections following a fever screening program in Taiwan,http://dx.doi.org/10.1186/1471-2334-12-182,PMC3462143,22867003,CC BY,"BACKGROUND: Dengue has not reached an endemic status in Taiwan; nevertheless, we have implemented a fever screening program at airports for the early detection of febrile passengers with a dengue infection. This study is intended to assess the performance of the airport screening procedures for dengue infection. METHODS: We analyzed data from the national surveillance system of the Taiwan Centers for Disease Control. We included the imported dengue cases reported by sentinel airports and clinics as well as the domestic cases from 2007–2010. RESULTS: Approximately 44.9% (95%CI: 35.73-54.13%) of the confirmed imported dengue cases with an apparent symptom (febrile) in the viremic stage were detected via the airport fever screening program, with an estimated positive predictive value of 2.36% (95% CI: 0.96- 3.75%) and a negative predictive value > 99.99%. Fluctuations in the number of the symptomatic imported dengue cases identified in the airports (X) were associated with the total number of imported dengue cases (Y) based on a regression analysis of a biweekly surveillance (i.e., n = 104, R(2)(X:Y) = 0.61, P < 0.005). Additionally, the fluctuating patterns in the cumulative numbers of the imported dengue cases (X) with a 1–2 month lead time (t) was in parallel with that of the domestic dengue cases (Y) based on a consecutive 4-year surveillance (i.e., n = 48, R(2)(X(t-1):Y) = 0.22, R(2)(X(t-2):Y) = 0.31, P < 0.001) from 2007–2010. CONCLUSIONS: A moderate sensitivity of detecting dengue at the airports examined in this study indicated some limitations of the fever screening program for the prevention of importation. The screening program could assist in the rapid triage for self-quarantine of some symptomatic dengue cases that were in the viremic stage at the borders and contribute to active sentinel surveillance; however, the blocking of viral transmission to susceptible populations (neighbors or family) from all of the viremic travelers, including those with or without symptoms, is critical to prevent dengue epidemics. Therefore, the reinforcement of mosquito bite prevention and household vector control in dengue-endemic or dengue-competent hotspots during an epidemic season is essential and highly recommended.",2012 Aug 6,"['Kuan, Mei-Mei', 'Chang, Feng-Yee']",BMC Infect Dis,,,True
2857cb1d4c6c446ac30ab4d0cabca0b42d62c465,PMC,The development of a GeXP-based multiplex reverse transcription-PCR assay for simultaneous detection of sixteen human respiratory virus types/subtypes,http://dx.doi.org/10.1186/1471-2334-12-189,PMC3462154,22891685,CC BY,"BACKGROUND: Existing standard non-molecular diagnostic methods such as viral culture and immunofluorescent (DFA) are time-consuming, labor intensive or limited sensitivity. Several multiplex molecular assays are costly. Therefore, there is a need for the development of a rapid and sensitive diagnosis of respiratory viral pathogens. METHODS: A GeXP-based multiplex RT-PCR assay (GeXP assay) was developed to detect simultaneously sixteen different respiratory virus types/subtypes. Seventeen sets of chimeric primers were used to initiate the RT-PCR, and one pair of universal primers was used for the subsequent cycles of the RT-PCR. The specificity of the GeXP assay was examined with positive controls for each virus type/subtype. The sensitivity was evaluated by performing the assay on serial ten-fold dilutions of in vitro-transcribed RNA of all RNA viruses and the plasmids containing the Adv and HBoV target sequence. GeXP assay was further evaluated using 126 clinical specimens and compared with Luminex xTAG RVP Fast assay. RESULTS: The GeXP assay achieved a sensitivity of 20–200 copies for a single virus and 1000 copies when all of the 16 pre-mixed viral targets were present. Analyses of 126 clinical specimens using the GeXP assay demonstrated that GeXP assay and the RVP Fast assay were in complete agreement for 109/126 (88.51%) of the specimens. GeXP assay was more sensitive than the RVP Fast assay for the detection of HRV and PIV3, and slightly less sensitive for the detection of HMPV, Adv, RSVB and HBoV. The whole process of the GeXP assay for the detection of 12 samples was completed within 2.5 hours. CONCLUSIONS: In conclusion, the GeXP assay is a rapid, cost-effective, sensitive, specific and high throughput method for the detection of respiratory virus infections.",2012 Aug 14,"['Li, Jin', 'Mao, Nai-Ying', 'Zhang, Chen', 'Yang, Meng-Jie', 'Wang, Miao', 'Xu, Wen-Bo', 'Ma, Xue-Jun']",BMC Infect Dis,,,True
a646c8ced739fd583e7e031a90e4936f2a764035,PMC,Dynamics of a Cytokine Storm,http://dx.doi.org/10.1371/journal.pone.0045027,PMC3462188,23049677,CC BY,"Six volunteers experienced severe inflammatory response during the Phase I clinical trial of a monoclonal antibody that was designed to stimulate a regulatory T cell response. Soon after the trial began, each volunteer experienced a “cytokine storm”, a dramatic increase in cytokine concentrations. The monoclonal antibody, TGN1412, raised serum concentrations of both pro- and anti-inflammatory cytokines το very hiγh values during the first day, while lymphocyte and monocyte concentrations plummeted. Because the subjects were healthy and had no prior indications of immune deficiency, this event provided an unusual opportunity to study the dynamic interactions of cytokines and other measured parameters. Here, the response histories of nine cytokines have been modeled by a set of linear ordinary differential equations. A general search procedure identifies parameters of the model, whose response fits the data well during the five-day measurement period. The eighteenth-order model reveals plausible cause-and-effect relationships among the cytokines, showing how each cytokine induces or inhibits other cytokines. It suggests that perturbations in IL2, IL8, and IL10 have the most significant inductive effect, while IFN-γ and IL12 have the greatest inhibiting effect on other cytokine concentrations. Although TNF-α is a major pro-inflammatory factor, IFN-γ and three other cytokines have faster initial and median response to TGN1412 infusion. Principal-component analysis of the data reveals three clusters of similar cytokine responses: [TNF-α, IL1, IL10], [IFN-γ, IL2, IL4, IL8, and IL12], and [IL6]. IL1, IL6, IL10, and TNF-α have the highest degree of variability in response to uncertain initial conditions, exogenous effects, and parameter estimates. This study illuminates details of a cytokine storm event, and it demonstrates the value of linear modeling for interpreting complex, coupled biological system dynamics from empirical data.",2012 Oct 1,"['Yiu, Hao Hong', 'Graham, Andrea L.', 'Stengel, Robert F.']",PLoS One,,,True
6cabb3c8d1e85384320c6d9f7c927f4abc93fd93,PMC,Flt3L Combined with Rapamycin Promotes Cardiac Allograft Tolerance by Inducing Regulatory Dendritic Cells and Allograft Autophagy in Mice,http://dx.doi.org/10.1371/journal.pone.0046230,PMC3462742,23056267,CC BY,"The induction of immune tolerance is still a formidable challenge in organ transplantation. Dendritic cells (DCs) play an important role in orchestrating immune responses by either mediating protective immune responses or inducing antigen specific tolerance. Previous studies demonstrated that the fms-like tyrosine kinase 3 receptor (Flt3) and its ligand (Flt3L) play an essential role in the regulation of DC commitment and development. Here, we report a synergic effect between Flt3L and low-dose rapamycin (Rapa) in the protection of allograft rejction. It was found that Flt3L combined with Rapa significantly prolonged murine cardiac allograft survival time as compared with that of untreated recipients or recipients treated with Rapa or Flt3L alone. Mechanistic studies revealed that Flt3L combined with low-dose of Rapa induced the generation of tolerogenic DCs along with the production of CD25(+) Foxp3(+) regulatory T cells and IL-10 secretion. We also observed enhanced autophagy in the cardiac allograft, which could be another asset contributing to the enhanced allograft survival. All together, these data suggest that Flt3L combined with low-dose of Rapa could be an effective therapeutic approach to induce tolerance in clinical setting of transplantation.",2012 Oct 2,"['Xiong, Ali', 'Duan, Lihua', 'Chen, Jie', 'Fan, Zhigang', 'Zheng, Fang', 'Tan, Zheng', 'Gong, Feili', 'Fang, Min']",PLoS One,,,True
04a253fd34bd82b3cf7868fca967469c66e392ab,PMC,RO 90-7501 Enhances TLR3 and RLR Agonist Induced Antiviral Response,http://dx.doi.org/10.1371/journal.pone.0042583,PMC3463586,23056170,CC BY,"Recognition of virus infection by innate pattern recognition receptors (PRRs), including membrane-associated toll-like receptors (TLR) and cytoplasmic RIG-I-like receptors (RLR), activates cascades of signal transduction pathways leading to production of type I interferons (IFN) and proinflammatory cytokines that orchestrate the elimination of the viruses. Although it has been demonstrated that PRR-mediated innate immunity plays an essential role in defending virus from infection, it also occasionally results in overwhelming production of proinflammatory cytokines that cause severe inflammation, blood vessel leakage and tissue damage. In our efforts to identify small molecules that selectively enhance PRR-mediated antiviral, but not the detrimental inflammatory response, we discovered a compound, RO 90–7501 (‘2’-(4-Aminophenyl)-[2,5′-bi-1H-benzimidazol]-5-amine), that significantly promoted both TLR3 and RLR ligand-induced IFN-β gene expression and antiviral response, most likely via selective activation of p38 mitogen-activated protein kinase (MAPK) pathway. Our results thus imply that pharmacological modulation of PRR signal transduction pathways in favor of the induction of a beneficial antiviral response can be a novel therapeutic strategy.",2012 Oct 3,"['Guo, Fang', 'Mead, Jennifer', 'Aliya, Nishat', 'Wang, Lijuan', 'Cuconati, Andrea', 'Wei, Lai', 'Li, Kui', 'Block, Timothy M.', 'Guo, Ju-Tao', 'Chang, Jinhong']",PLoS One,,,True
628b63978a499c7cdecbccf06dd60980da895fb0,PMC,Renalase's Expression and Distribution in Renal Tissue and Cells,http://dx.doi.org/10.1371/journal.pone.0046442,PMC3463591,23056310,CC BY,"To study renalase's expression and distribution in renal tissues and cells, renalase coded DNA vaccine was constructed, and anti-renalase monoclonal antibodies were produced using DNA immunization and hybridoma technique, followed by further investigation with immunological testing and western blotting to detect the expression and distribution of renalase among the renal tissue and cells. Anti-renalase monoclonal antibodies were successfully prepared by using DNA immunization technique. Further studies with anti-renalase monoclonal antibody showed that renalase expressed in glomeruli, tubule, mesangial cells, podocytes, renal tubule epithelial cells and its cells supernatant. Renalase is wildly expressed in kidney, including glomeruli, tubule, mesangial cells, podocytes and tubule epithelial cells, and may be secreted by tubule epithelial cells primarily.",2012 Oct 3,"['Wang, Feng', 'Xing, Tao', 'Li, Junhui', 'Bai, Mei', 'Hu, Ruimin', 'Zhao, Zhonghua', 'Tian, Shoufu', 'Zhang, Zhigang', 'Wang, Niansong']",PLoS One,,,True
03b9acce84a4799d4be1152a36abfaf52fb3b523,PMC,Representative Contact Diaries for Modeling the Spread of Infectious Diseases in Taiwan,http://dx.doi.org/10.1371/journal.pone.0045113,PMC3463600,23056193,CC BY,"Recent studies of infectious diseases have attempted to construct more realistic parameters of interpersonal contact patterns from diary-approach surveys. To ensure that such diary-based contact patterns provide accurate baseline data for policy implementation in densely populated Taiwan, we collected contact diaries from a national sample, using 3-stage systematic probability sampling and rigorous in-person interviews. A representative sample of 1,943 contact diaries recorded a total of 24,265 wide-range, face-to-face interpersonal contacts during a 24-hour period. Nearly 70% of the contacts occurred outside of respondents' households. The most active age group was schoolchildren (ages 5–14), who averaged around 16–18 daily contacts, about 2–3 times as many as the least active age groups. We show how such parameters of contact patterns help modify a sophisticated national simulation system that has been used for years to model the spread of pandemic diseases in Taiwan. Based on such actual and representative data that enable researchers to infer findings to the whole population, our analyses aim to facilitate implementing more appropriate and effective strategies for controlling an emerging or pandemic disease infection.",2012 Oct 3,"['Fu, Yang-chih', 'Wang, Da-Wei', 'Chuang, Jen-Hsiang']",PLoS One,,,True
4501afb17c42f81f10cefa7c72ef331c15f61fb9,PMC,DENV Inhibits Type I IFN Production in Infected Cells by Cleaving Human STING,http://dx.doi.org/10.1371/journal.ppat.1002934,PMC3464218,23055924,CC BY,"Dengue virus (DENV) is a pathogen with a high impact on human health. It replicates in a wide range of cells involved in the immune response. To efficiently infect humans, DENV must evade or inhibit fundamental elements of the innate immune system, namely the type I interferon response. DENV circumvents the host immune response by expressing proteins that antagonize the cellular innate immunity. We have recently documented the inhibition of type I IFN production by the proteolytic activity of DENV NS2B3 protease complex in human monocyte derived dendritic cells (MDDCs). In the present report we identify the human adaptor molecule STING as a target of the NS2B3 protease complex. We characterize the mechanism of inhibition of type I IFN production in primary human MDDCs by this viral factor. Using different human and mouse primary cells lacking STING, we show enhanced DENV replication. Conversely, mutated versions of STING that cannot be cleaved by the DENV NS2B3 protease induced higher levels of type I IFN after infection with DENV. Additionally, we show that DENV NS2B3 is not able to degrade the mouse version of STING, a phenomenon that severely restricts the replication of DENV in mouse cells, suggesting that STING plays a key role in the inhibition of DENV infection and spread in mice.",2012 Oct 4,"['Aguirre, Sebastian', 'Maestre, Ana M.', 'Pagni, Sarah', 'Patel, Jenish R.', 'Savage, Timothy', 'Gutman, Delia', 'Maringer, Kevin', 'Bernal-Rubio, Dabeiba', 'Shabman, Reed S.', 'Simon, Viviana', 'Rodriguez-Madoz, Juan R.', 'Mulder, Lubbertus C. F.', 'Barber, Glen N.', 'Fernandez-Sesma, Ana']",PLoS Pathog,,,True
3c83a45d3f3e227de8b5e0e88022352385dd78e8,PMC,Impact of drug price adjustments on utilization of and expenditures on angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in Taiwan,http://dx.doi.org/10.1186/1471-2458-12-288,PMC3464938,22521158,CC BY,"BACKGROUND: A previous study has suggested that drug price adjustments allow physicians in Taiwan to gain greater profit by prescribing generic drugs. To better understand the effect of price adjustments on physician choice, this study used renin-angiotensin drugs (including angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs]) to examine the impact of price adjustments on utilization of and expenditures on patented and off-patent drugs with the same therapeutic indication. METHODS: Using the Taiwan’s Longitudinal Health Insurance Database (2005), we identified 147,157 patients received ACEIs and/or ARBs between 1997 and 2008. The annual incident and prevalent users of ACEIs, ARBs and overall renin-angiotensin drugs were examined. Box-Tiao intervention analysis was applied to assess the impact of price adjustments on monthly utilization of and expenditures on these drugs. ACEIs were divided into patented and off-patent drugs, off-patent ACEIs were further divided into original brands and generics, and subgroup analyses were performed. RESULTS: The number of incident renin-angiotensin drug users decreased over the study period. The number of prevalent ARB users increased and exceeded the cumulative number of first-time renin-angiotensin drug users starting on ARBs, implying that some patients switched from ACEIs to ARBs. After price adjustments, long term trend increases in utilization were observed for patented ACEIs and ARBs; a long-term trend decrease was observed for off-patent ACEIs; long-term trend change was not significant for overall renin-angiotensin drugs. Significant long-term trend increases in expenditures were observed for patented ACEIs after price adjustment in 2007 (200.9%, p = 0.0088) and in ARBs after price adjustments in 2001 (173.4%, p < 0.0001) and 2007 (146.3%, p < 0.0001). A significant long-term trend decrease in expenditures was observed for off-patent ACEIs after 2004 price adjustment (−156.9%, p < 0.0001). Expenditures on overall renin-angiotensin drugs showed long-term trend increases after price adjustments in 2001 (72.2%, p < 0.0001) and 2007 (133.4%, p < 0.0001). CONCLUSIONS: Price adjustments did not achieve long-term cost savings for overall renin-angiotensin drugs. Possible switching from ACEIs to ARBs within individuals is evident. Policy makers should reconsider the appropriateness of the current adjustment strategies applied to patented and off-patent drugs.",2012 Apr 20,"['Huang, Shiou-Huei', 'Hsu, Chien-Ning', 'Yu, Shu-Hui', 'Cham, Thau-Ming']",BMC Public Health,,,True
5ee02e510d7fb0b2523b669dacadf4f56ee6b55f,PMC,Impact of drug price adjustments on utilization of and expenditures on angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in Taiwan,http://dx.doi.org/10.1186/1471-2458-12-288,PMC3464938,22521158,CC BY,"BACKGROUND: A previous study has suggested that drug price adjustments allow physicians in Taiwan to gain greater profit by prescribing generic drugs. To better understand the effect of price adjustments on physician choice, this study used renin-angiotensin drugs (including angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs]) to examine the impact of price adjustments on utilization of and expenditures on patented and off-patent drugs with the same therapeutic indication. METHODS: Using the Taiwan’s Longitudinal Health Insurance Database (2005), we identified 147,157 patients received ACEIs and/or ARBs between 1997 and 2008. The annual incident and prevalent users of ACEIs, ARBs and overall renin-angiotensin drugs were examined. Box-Tiao intervention analysis was applied to assess the impact of price adjustments on monthly utilization of and expenditures on these drugs. ACEIs were divided into patented and off-patent drugs, off-patent ACEIs were further divided into original brands and generics, and subgroup analyses were performed. RESULTS: The number of incident renin-angiotensin drug users decreased over the study period. The number of prevalent ARB users increased and exceeded the cumulative number of first-time renin-angiotensin drug users starting on ARBs, implying that some patients switched from ACEIs to ARBs. After price adjustments, long term trend increases in utilization were observed for patented ACEIs and ARBs; a long-term trend decrease was observed for off-patent ACEIs; long-term trend change was not significant for overall renin-angiotensin drugs. Significant long-term trend increases in expenditures were observed for patented ACEIs after price adjustment in 2007 (200.9%, p = 0.0088) and in ARBs after price adjustments in 2001 (173.4%, p < 0.0001) and 2007 (146.3%, p < 0.0001). A significant long-term trend decrease in expenditures was observed for off-patent ACEIs after 2004 price adjustment (−156.9%, p < 0.0001). Expenditures on overall renin-angiotensin drugs showed long-term trend increases after price adjustments in 2001 (72.2%, p < 0.0001) and 2007 (133.4%, p < 0.0001). CONCLUSIONS: Price adjustments did not achieve long-term cost savings for overall renin-angiotensin drugs. Possible switching from ACEIs to ARBs within individuals is evident. Policy makers should reconsider the appropriateness of the current adjustment strategies applied to patented and off-patent drugs.",2012 Apr 20,"['Huang, Shiou-Huei', 'Hsu, Chien-Ning', 'Yu, Shu-Hui', 'Cham, Thau-Ming']",BMC Public Health,,,True
03d7c96afa37141562c3ac9297882dbe59d2e0e4,PMC,Simultaneous investigation of influenza and enteric viruses in the stools of adult patients consulting in general practice for acute diarrhea,http://dx.doi.org/10.1186/1743-422X-9-116,PMC3466123,22709374,CC BY,"BACKGROUND: Gastrointestinal symptoms are not an uncommon manifestation of an influenza virus infection. In the present study, we aimed to investigate the presence of influenza viruses in the stools of adult patients consulting their general practitioner for uncomplicated acute diarrhea (AD) and the proportion of concurrent infections by enteric and influenza viruses. METHOD: A case-control study was conducted from December 2010 to April 2011. Stool specimens were collected and tested for influenza viruses A (seasonal A/H3N2 and pandemic A/H1N1) and B, and for four enteric viruses (astrovirus, group A rotavirus, human enteric adenovirus, norovirus of genogroups I – NoVGI - and genogroup II - NoVGII). RESULTS: General practitioners enrolled 138 cases and 93 controls. Of the 138 stool specimens collected, 92 (66.7%) were positive for at least one of the four enteric viruses analysed and 10 (7.2%) tested positive for one influenza virus. None of these 10 influenza positive patients reported respiratory symptoms. In five influenza-positive patients (3.6%), we also detected one enteric virus, with 4 of them being positive for influenza B (2 had co-detection with NoVGI, 1 with NoVGII, and 1 with astrovirus). None of the 93 controls tested positive for one of the enteric and/or other influenza viruses we investigated. CONCLUSIONS: In this study we showed that the simultaneous detection of influenza and enteric viruses is not a rare event. We have also reported, for the first time in general practice, the presence of seasonal and pandemic influenza viruses in the stools of adult patients consulting for uncomplicated AD. A simultaneous investigation of enteric and influenza viruses in patients complaining of gastrointestinal symptoms could be useful for future studies to better identify the agents responsible for AD.",2012 Jun 18,"['Arena, Christophe', 'Amoros, Jean Pierre', 'Vaillant, Véronique', 'Balay, Katia', 'Chikhi-Brachet, Roxane', 'Varesi, Laurent', 'Arrighi, Jean', 'Blanchon, Thierry', 'Carrat, Fabrice', 'Hanslik, Thomas', 'Falchi, Alessandra']",Virol J,,,True
6135c4bb442a034b18ef4e9b3fc5701507225f0d,PMC,Acute Reactogenicity after Intramuscular Immunization with Recombinant Vesicular Stomatitis Virus Is Linked to Production of IL-1β,http://dx.doi.org/10.1371/journal.pone.0046516,PMC3466325,23056330,CC BY,"Vaccines based on live viruses are attractive because they are immunogenic, cost-effective, and can be delivered by multiple routes. However, live virus vaccines also cause reactogenic side effects such as fever, myalgia, and injection site pain that have reduced their acceptance in the clinic. Several recent studies have linked vaccine-induced reactogenic side effects to production of the pro-inflammatory cytokine interleukin-1β (IL-1β) in humans. Our objective was therefore to determine whether IL-1β contributed to pathology after immunization with recombinant vesicular stomatitis virus (rVSV) vaccine vectors, and if so, to identify strategies by which IL-1β mediated pathology might be reduced without compromising immunogenicity. We found that an rVSV vaccine induced local and systemic production of IL-1β in vivo, and that accumulation of IL-1β correlated with acute pathology after rVSV immunization. rVSV-induced pathology was reduced in mice deficient in the IL-1 receptor Type I, but the IL-1R−/− mice were fully protected from lethal rechallenge with a high dose of VSV. This result demonstrated that IL-1 contributed to reactogenicity of the rVSV, but was dispensable for induction of protective immunity. The amount of IL-1β detected in mice deficient in either caspase-1 or the inflammasome adaptor molecule ASC after rVSV immunization was not significantly different than that produced by wild type animals, and caspase-1−/− and ASC−/− mice were only partially protected from rVSV-induced pathology. Those data support the idea that some of the IL-1β expressed in vivo in response to VSV may be activated by a caspase-1 and ASC-independent mechanism. Together these results suggest that rVSV vectors engineered to suppress the induction of IL-1β, or signaling through the IL-1R would be less reactogenic in vivo, but would retain their immunogenicity and protective capacity. Such rVSV would be highly desirable as either vaccine vectors or oncolytic therapies, and would likely be better tolerated in human vaccinees.",2012 Oct 8,"['Athearn, Kathleen', 'Sample, Christopher J.', 'Barefoot, Brice E.', 'Williams, Kristi L.', 'Ramsburg, Elizabeth A.']",PLoS One,,,True
d672ce4063b2033261865d54cc7db91b9186beee,PMC,Oroxylin-A Rescues LPS-Induced Acute Lung Injury via Regulation of NF-κB Signaling Pathway in Rodents,http://dx.doi.org/10.1371/journal.pone.0047403,PMC3468516,23071799,CC BY,"BACKGROUND AND PURPOSE: Successful drug treatment for sepsis-related acute lung injury (ALI) remains a major clinical problem. This study was designed to assess the beneficial effects of post-treatment of oroxylin A (OroA), a flavonoid, in ameliorating lipopolysaccharides (LPS)-induced lung inflammation and fatality. EXPERIMENTAL APPROACH: Rats were injected with LPS (10 mg/kg, iv) to induce ALI, and OroA was given (15 mg/kg, iv) 1 hr or 6 hrs after LPS challenge. Twenty four hrs after LPS challenge, biochemical changes in the blood and lung tissues, and morphological/histological alterations in the lung associated with inflammation and injury were examined. Therapeutic effect of OroA was assessed by measuring the survival rate in endotoxemic mice. KEY RESULTS: LPS (10 mg/kg, iv) significantly altered WBC counts, elevated plasma tumor necrosis factor (TNF)-α and nitric oxide (NO), increased pulmonary edema, thickened alveolar septa, and decreased survival rate. These changes were ameliorated by OroA (15 mg/kg, iv) administered 1 hr or 6 hrs after LPS challenge. This post-treatment also significantly attenuated LPS-induced activation of nuclear factor-κB (NF-κB) and the release of high mobility group box 1 (HMGB1) in lung tissues. Furthermore, post-treatment with OroA (60 mg/kg, ip) administered 1 hr or 6 hrs after LPS challenge in mice significantly increased survival rate. CONCLUSION AND IMPLICATION: OroA administered after induction of ALI by LPS significantly prevent and revere lung tissues injuries with increased survival rate. Positive post-treatment effects of OroA suggest that OroA is a potentially useful candidate for managing lung inflammation in LPS-induced endotoxemia and septic shock.",2012 Oct 10,"['Tseng, Tzu-Ling', 'Chen, Mei-Fang', 'Tsai, Ming-Jen', 'Hsu, Yung-Hsiang', 'Chen, Chin-Piao', 'Lee, Tony J. F.']",PLoS One,,,True
2431c74630bb92f71e47e7f1c89054cef368ace0,PMC,"Introducing Alphitobius diaperinus, (Insecta: Tenebrionidae) as a New Intermediate Host of Hadjelia truncata (Nematoda)",,PMC3469194,23109952,CC BY,"BACKGROUND: Hadjelia truncata is a nematode that causes lesions in the gizzard lining of pigeons, which may even lead to death. The aim of this study was to introduce Alphitobius diaperinus as a new intermediate host for Hadjelia truncata. METHODS: H. truncata infection was identified in a pigeon flock in Ahvaz City, Khuzestan Province, Iran by performing fecal examination and autopsy. Adult and larval stages of beetles were collected from the litter of pigeon houses, and identified morphologically. The beetle larvae were cultured in a medium, containing feces of the infected pigeons. Nematode larval stages from naturally and experimentally (culturally) infected adult beetles were fed to two groups of pigeons RESULTS: The collected beetles were identified as Alphitobius diaperinus. Average length and width of the adult beetles were 6.31 mm and 2.88 mm respectively. Infection rates of naturally and experimentally infected beetles with larval stages of the nematode were 66.2% and 45.1% respectively. The adult nematodes collected from gizzards of experimentally infected pigeons were identified as H. truncata. Nematode infection rates in pigeons after feeding the infective larvae collected from naturally and experimentally infected beetles were 44.7% and 32.5% respectively. CONCLUSION: A. diaperinus can serve as a natural intermediate host for H. truncata.",2012,"['Alborzi, AR', 'Rahbar, A']",Iran J Parasitol,,,True
bf4d08eb7675759c77b722b7509bea52906930da,PMC,Competition between Influenza A Virus Genome Segments,http://dx.doi.org/10.1371/journal.pone.0047529,PMC3469491,23071819,CC BY,"Influenza A virus (IAV) contains a segmented negative-strand RNA genome. How IAV balances the replication and transcription of its multiple genome segments is not understood. We developed a dual competition assay based on the co-transfection of firefly or Gaussia luciferase-encoding genome segments together with plasmids encoding IAV polymerase subunits and nucleoprotein. At limiting amounts of polymerase subunits, expression of the firefly luciferase segment was negatively affected by the presence of its Gaussia luciferase counterpart, indicative of competition between reporter genome segments. This competition could be relieved by increasing or decreasing the relative amounts of firefly or Gaussia reporter segment, respectively. The balance between the luciferase expression levels was also affected by the identity of the untranslated regions (UTRs) as well as segment length. In general it appeared that genome segments displaying inherent higher expression levels were more efficient competitors of another segment. When natural genome segments were tested for their ability to suppress reporter gene expression, shorter genome segments generally reduced firefly luciferase expression to a larger extent, with the M and NS segments having the largest effect. The balance between different reporter segments was most dramatically affected by the introduction of UTR panhandle-stabilizing mutations. Furthermore, only reporter genome segments carrying these mutations were able to efficiently compete with the natural genome segments in infected cells. Our data indicate that IAV genome segments compete for available polymerases. Competition is affected by segment length, coding region, and UTRs. This competition is probably most apparent early during infection, when limiting amounts of polymerases are present, and may contribute to the regulation of segment-specific replication and transcription.",2012 Oct 11,"['Widjaja, Ivy', 'de Vries, Erik', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.']",PLoS One,,,True
e57993034cb1196b96daff4505db38640782f4a0,PMC,An Analysis of Regulatory T-Cell and Th-17 Cell Dynamics during Cytomegalovirus Replication in Solid Organ Transplant Recipients,http://dx.doi.org/10.1371/journal.pone.0043937,PMC3469568,23071829,CC BY,"BACKGROUND: CMV-specific T-cells are crucial to control CMV-replication post-transplant. Regulatory T-cells (T-regs) are associated with a tolerant immune state and may contribute to CMV-replication. However, T-cell subsets such as T-regs and IL-17 producing T-cells (Th-17) are not well studied in this context. We explored T-regs and Th-17 frequencies during CMV-replication after transplantation. METHODS: We prospectively evaluated 30 transplant patients with CMV-viremia. We quantified CMV-specific CD4(+) and CD8(+) T-cells, T-regs (CD4(+)CD25(+)FoxP3(+)) and Th-17 frequencies using flow-cytometry and followed patients requiring anti-viral treatment. Two subsets were compared: anti-viral treatment requirement (n = 20) vs. spontaneous clearance of viremia (n = 10). RESULTS: Higher initial CMV-specific CD4(+) T-cells and lower T-regs were observed in patients with spontaneous clearance (p = 0.043; p = 0.021 respectively). Using a ratio of CMV-specific CD4(+) T-cells to T-regs allowed prediction of viral clearance with 80% sensitivity and 90% specificity (p = 0.001). One month after stop of treatment, the same correlation was observed in patients protected from CMV-relapse. The ratio of CMV-specific CD4(+) T-cells to T-regs allowed prediction of relapse with 85% sensitivity and 86% specificity (p = 0.004). Th-17 responses were not correlated with virologic outcomes. CONCLUSIONS: This study provides novel insights into T-regs and Th-17 subpopulations during CMV-replication after transplantation. These preliminary data suggest that measurement of CMV-specific CD4(+) T-cells together with T-regs has value in predicting spontaneous clearance of viremia and relapse.",2012 Oct 11,"['Egli, Adrian', 'Silva, Moacyr', ""O'Shea, Daire"", 'Wilson, Leticia E.', 'Baluch, Aliyah', 'Lisboa, Luiz F.', 'Hidalgo, Luis G.', 'Kumar, Deepali', 'Humar, Atul']",PLoS One,,,True
bbc2824ce7dff3d23d060b7abbe96cba28095fb8,PMC,Respiratory viral infections in children with asthma: do they matter and can we prevent them?,http://dx.doi.org/10.1186/1471-2431-12-147,PMC3471019,22974166,CC BY,"BACKGROUND: Asthma is a major public health problem with a huge social and economic burden affecting 300 million people worldwide. Viral respiratory infections are the major cause of acute asthma exacerbations and may contribute to asthma inception in high risk young children with susceptible genetic background. Acute exacerbations are associated with decreased lung growth or accelerated loss of lung function and, as such, add substantially to both the cost and morbidity associated with asthma. DISCUSSION: While the importance of preventing viral infection is well established, preventive strategies have not been well explored. Good personal hygiene, hand-washing and avoidance of cigarette smoke are likely to reduce respiratory viral infections. Eating a healthy balanced diet, active probiotic supplements and bacterial-derived products, such as OM-85, may reduce recurrent infections in susceptible children. There are no practical anti-viral therapies currently available that are suitable for widespread use. SUMMARY: Hand hygiene is the best measure to prevent the common cold. A healthy balanced diet, active probiotic supplements and immunostimulant OM-85 may reduce recurrent infections in asthmatic children.",2012 Sep 13,"['Ahanchian, Hamid', 'Jones, Carmen M', 'Chen, Yueh-sheng', 'Sly, Peter D']",BMC Pediatr,,,True
e4dedf2b46618a544180539e2a2943c3618b8fec,PMC,Label-Free Electrochemical Diagnosis of Viral Antigens with Genetically Engineered Fusion Protein,http://dx.doi.org/10.3390/s120810097,PMC3472818,23112590,CC BY,"We have developed a simple electrochemical biosensing strategy for the label-free diagnosis of hepatitis B virus (HBV) on a gold electrode surface. Gold-binding polypeptide (GBP) fused with single-chain antibody (ScFv) against HBV surface antigen (HBsAg), in forms of genetically engineered protein, was utilized. This GBP-ScFv fusion protein can directly bind onto the gold substrate with the strong binding affinity between the GBP and the gold surface, while the recognition site orients toward the sample for target binding at the same time. Furthermore, this one-step immobilization strategy greatly simplifies a fabrication process without any chemical modification as well as maintaining activity of biological recognition elements. This system allows specific immobilization of proteins and sensitive detection of targets, which were verified by surface plasmon resonance analysis and successfully applied to electrochemical cyclic voltammetry and impedance spectroscopy upto 0.14 ng/mL HBsAg.",2012 Jul 26,"['Heo, Nam Su', 'Zheng, Shun', 'Yang, MinHo', 'Lee, Seok Jae', 'Lee, Sang Yup', 'Kim, Hwa-Jung', 'Park, Jung Youn', 'Lee, Chang-Soo', 'Park, Tae Jung']",Sensors (Basel),,,True
cf96fbb3db5c01498ecd4d4a48a09f395e038343,PMC,Label-Free Electrochemical Diagnosis of Viral Antigens with Genetically Engineered Fusion Protein,http://dx.doi.org/10.3390/s120810097,PMC3472818,23112590,CC BY,"We have developed a simple electrochemical biosensing strategy for the label-free diagnosis of hepatitis B virus (HBV) on a gold electrode surface. Gold-binding polypeptide (GBP) fused with single-chain antibody (ScFv) against HBV surface antigen (HBsAg), in forms of genetically engineered protein, was utilized. This GBP-ScFv fusion protein can directly bind onto the gold substrate with the strong binding affinity between the GBP and the gold surface, while the recognition site orients toward the sample for target binding at the same time. Furthermore, this one-step immobilization strategy greatly simplifies a fabrication process without any chemical modification as well as maintaining activity of biological recognition elements. This system allows specific immobilization of proteins and sensitive detection of targets, which were verified by surface plasmon resonance analysis and successfully applied to electrochemical cyclic voltammetry and impedance spectroscopy upto 0.14 ng/mL HBsAg.",2012 Jul 26,"['Heo, Nam Su', 'Zheng, Shun', 'Yang, MinHo', 'Lee, Seok Jae', 'Lee, Sang Yup', 'Kim, Hwa-Jung', 'Park, Jung Youn', 'Lee, Chang-Soo', 'Park, Tae Jung']",Sensors (Basel),,,False
a4ac0a556416712bc053f001c5bc6931c908bfd1,PMC,Development of a Plastic-Based Microfluidic Immunosensor Chip for Detection of H1N1 Influenza,http://dx.doi.org/10.3390/s120810810,PMC3472858,23112630,CC BY,"Lab-on-a-chip can provide convenient and accurate diagnosis tools. In this paper, a plastic-based microfluidic immunosensor chip for the diagnosis of swine flu (H1N1) was developed by immobilizing hemagglutinin antigen on a gold surface using a genetically engineered polypeptide. A fluorescent dye-labeled antibody (Ab) was used for quantifying the concentration of Ab in the immunosensor chip using a fluorescent technique. For increasing the detection efficiency and reducing the errors, three chambers and three microchannels were designed in one microfluidic chip. This protocol could be applied to the diagnosis of other infectious diseases in a microfluidic device.",2012 Aug 6,"['Lee, Kyoung G.', 'Lee, Tae Jae', 'Jeong, Soon Woo', 'Choi, Ho Woon', 'Heo, Nam Su', 'Park, Jung Youn', 'Park, Tae Jung', 'Lee, Seok Jae']",Sensors (Basel),,,True
75396899537915606b74f2b600478ad066f9d594,PMC,Hepatitis C VLPs Delivered to Dendritic Cells by a TLR2 Targeting Lipopeptide Results in Enhanced Antibody and Cell-Mediated Responses,http://dx.doi.org/10.1371/journal.pone.0047492,PMC3472981,23091628,CC BY,"Although many studies provide strong evidence supporting the development of HCV virus-like particle (VLP)-based vaccines, the fact that heterologous viral vectors and/or multiple dosing regimes are required to induce protective immunity indicates that it is necessary to improve their immunogenicity. In this study, we have evaluated the use of an anionic self-adjuvanting lipopeptide containing the TLR2 agonist Pam(2)Cys (E(8)Pam(2)Cys) to enhance the immunogenicity of VLPs containing the HCV structural proteins (core, E1 and E2) of genotype 1a. While co-formulation of this lipopeptide with VLPs only resulted in marginal improvements in dendritic cell (DC) uptake, its ability to concomitantly induce DC maturation at very small doses is a feature not observed using VLPs alone or in the presence of an aluminium hydroxide-based adjuvant (Alum). Dramatically improved VLP and E2-specific antibody responses were observed in VLP+E(8)Pam(2)Cys vaccinated mice where up to 3 doses of non-adjuvanted or traditionally alum-adjuvanted VLPs was required to match the antibody titres obtained with a single dose of VLPs formulated with this lipopeptide. This result also correlated with significantly higher numbers of specific antibody secreting cells that was detected in the spleens of VLP+E(8)Pam(2)Cys vaccinated mice and greater ability of sera from these mice to neutralise the binding and uptake of VLPs by Huh7 cells. Moreover, vaccination of HLA-A2 transgenic mice with this formulation also induced better VLP-specific IFN-γ-mediated responses compared to non-adjuvanted VLPs but comparable levels to that achieved when coadministered with complete freund’s adjuvant. These results suggest overall that the immunogenicity of HCV VLPs can be significantly improved by the addition of this novel adjuvant by targeting their delivery to DCs and could therefore constitute a viable vaccine strategy for the treatment of HCV.",2012 Oct 16,"['Chua, Brendon Y.', 'Johnson, Douglas', 'Tan, Amabel', 'Earnest-Silveira, Linda', 'Sekiya, Toshiki', 'Chin, Ruth', 'Torresi, Joseph', 'Jackson, David C.']",PLoS One,,,True
96782ada9704aca0076d39f6e2592c521d8a5383,PMC,Both STING and MAVS Fish Orthologs Contribute to the Induction of Interferon Mediated by RIG-I,http://dx.doi.org/10.1371/journal.pone.0047737,PMC3473018,23091644,CC BY,"Viral infections are detected in most cases by the host innate immune system through pattern-recognition receptors (PRR), the sensors for pathogen-associated molecular patterns (PAMPs), which induce the production of cytokines, such as type I interferons (IFN). Recent identification in mammalian and teleost fish of cytoplasmic viral RNA sensors, RIG-I-like receptors (RLRs), and their mitochondrial adaptor: the mitochondrial antiviral signaling (MAVS) protein, also called IPS-1, highlight their important role in the induction of IFN at the early stage of a virus infection. More recently, an endoplasmic reticulum (ER) adaptor: the stimulator of interferon genes (STING) protein, also called MITA, ERIS and MPYS, has been shown to play a pivotal role in response to both non-self-cytosolic RNA and dsDNA. In this study, we cloned STING cDNAs from zebrafish and showed that it was an ortholog to mammalian STING. We demonstrated that overexpression of this ER protein in fish cells led to a constitutive induction of IFN and interferon-stimulated genes (ISGs). STING-overexpressing cells were almost fully protected against RNA virus infection with a strong inhibition of both DNA and RNA virus replication. In addition, we found that together with MAVS, STING was an important player in the RIG-I IFN-inducing pathway. This report provides the demonstration that teleost fish possess a functional RLR pathway in which MAVS and STING are downstream signaling molecules of RIG-I. The Sequences presented in this article have been submitted to GenBank under accession numbers: Zebrafish STING (HE856619); EPC STING (HE856620); EPC IRF3 (HE856621); EPC IFN promoter (HE856618).",2012 Oct 16,"['Biacchesi, Stéphane', 'Mérour, Emilie', 'Lamoureux, Annie', 'Bernard, Julie', 'Brémont, Michel']",PLoS One,,,True
1952a38871ef31c0e837ff0ee666bd0350c8b32c,PMC,Infectious diseases in healthcare workers – an analysis of the standardised data set of a German compensation board,http://dx.doi.org/10.1186/1745-6673-7-8,PMC3474162,22553942,CC BY,"INTRODUCTION: Healthcare workers (HCW) are exposed to infectious agents. Disease surveillance is therefore needed in order to foster prevention. METHODS: The data of the compensation board that covers HCWs of non-governmental healthcare providers in Germany was analysed for a five-year period. For hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, the period analysed was extended to the last 15 years. The annual rate of occupational infectious diseases (OIDs) per 100,000 employees was calculated. For needlestick injuries (NSI) a rate per 1,000 employees was calculated. RESULTS: Within the five years from 2005 to 2009 a total of 384 HCV infections were recognised as OIDs (1.5/100,000 employees). Active TB was the second most frequent cause of an OID. While the numbers of HBV and HCV infections decreased, the numbers for active TB did not follow a clear pattern. Needlestick injuries (NSIs) were reported especially often at hospitals (29.9/1,000 versus 7.4/1,000 employees for all other HCWs). CONCLUSION: Although they are declining, HCV infections remain frequent in HCWs, as do NSIs. Whether the reinforcement of the recommendations for the use of safety devices in Germany will prevent NSIs and therefore HCV infections should be closely observed.",2012 May 3,"['Nienhaus, Albert', 'Kesavachandran, Chandrasekharan', 'Wendeler, Dana', 'Haamann, Frank', 'Dulon, Madeleine']",J Occup Med Toxicol,,,True
7bf54447fa81cd0f3c36e6e6455e80241fe82b0a,PMC,Associations between Pathogens in the Upper Respiratory Tract of Young Children: Interplay between Viruses and Bacteria,http://dx.doi.org/10.1371/journal.pone.0047711,PMC3474735,23082199,CC BY,"BACKGROUND: High rates of potentially pathogenic bacteria and respiratory viruses can be detected in the upper respiratory tract of healthy children. Investigating presence of and associations between these pathogens in healthy individuals is still a rather unexplored field of research, but may have implications for interpreting findings during disease. METHODOLOGY/PRINCIPAL FINDINGS: We selected 986 nasopharyngeal samples from 433 6- to 24-month-old healthy children that had participated in a randomized controlled trial. We determined the presence of 20 common respiratory viruses using real-time PCR. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus were identified by conventional culture methods. Information on risk factors was obtained by questionnaires. We performed multivariate logistic regression analyses followed by partial correlation analysis to identify the overall pattern of associations. S. pneumoniae colonization was positively associated with the presence of H. influenzae (adjusted odds ratio 1.60, 95% confidence interval 1.18–2.16), M. catarrhalis (1.78, 1.29–2.47), human rhinoviruses (1.63, 1.19–2.22) and enteroviruses (1.97, 1.26–3.10), and negatively associated with S. aureus presence (0.59, 0.35–0.98). H. influenzae was positively associated with human rhinoviruses (1.63, 1.22–2.18) and respiratory syncytial viruses (2.78, 1.06–7.28). M. catarrhalis colonization was positively associated with coronaviruses (1.99, 1.01–3.93) and adenoviruses (3.69, 1.29–10.56), and negatively with S. aureus carriage (0.42, 0.25–0.69). We observed a strong positive association between S. aureus and influenza viruses (4.87, 1.59–14.89). In addition, human rhinoviruses and enteroviruses were positively correlated (2.40, 1.66–3.47), as were enteroviruses and human bocavirus, WU polyomavirus, parainfluenza viruses, and human parechovirus. A negative association was observed between human rhinoviruses and coronaviruses. CONCLUSIONS/SIGNIFICANCE: Our data revealed high viral and bacterial prevalence rates and distinct bacterial-bacterial, viral-bacterial and viral-viral associations in healthy children, hinting towards the complexity and potential dynamics of microbial communities in the upper respiratory tract. This warrants careful consideration when associating microbial presence with specific respiratory diseases.",2012 Oct 17,"['van den Bergh, Menno R.', 'Biesbroek, Giske', 'Rossen, John W. A.', 'de Steenhuijsen Piters, Wouter A. A.', 'Bosch, Astrid A. T. M.', 'van Gils, Elske J. M.', 'Wang, Xinhui', 'Boonacker, Chantal W. B.', 'Veenhoven, Reinier H.', 'Bruin, Jacob P.', 'Bogaert, Debby', 'Sanders, Elisabeth A. M.']",PLoS One,,,True
d998f77730919d75aa1d19fc3009531447a4d849,PMC,Associations between Pathogens in the Upper Respiratory Tract of Young Children: Interplay between Viruses and Bacteria,http://dx.doi.org/10.1371/journal.pone.0047711,PMC3474735,23082199,CC BY,"BACKGROUND: High rates of potentially pathogenic bacteria and respiratory viruses can be detected in the upper respiratory tract of healthy children. Investigating presence of and associations between these pathogens in healthy individuals is still a rather unexplored field of research, but may have implications for interpreting findings during disease. METHODOLOGY/PRINCIPAL FINDINGS: We selected 986 nasopharyngeal samples from 433 6- to 24-month-old healthy children that had participated in a randomized controlled trial. We determined the presence of 20 common respiratory viruses using real-time PCR. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus were identified by conventional culture methods. Information on risk factors was obtained by questionnaires. We performed multivariate logistic regression analyses followed by partial correlation analysis to identify the overall pattern of associations. S. pneumoniae colonization was positively associated with the presence of H. influenzae (adjusted odds ratio 1.60, 95% confidence interval 1.18–2.16), M. catarrhalis (1.78, 1.29–2.47), human rhinoviruses (1.63, 1.19–2.22) and enteroviruses (1.97, 1.26–3.10), and negatively associated with S. aureus presence (0.59, 0.35–0.98). H. influenzae was positively associated with human rhinoviruses (1.63, 1.22–2.18) and respiratory syncytial viruses (2.78, 1.06–7.28). M. catarrhalis colonization was positively associated with coronaviruses (1.99, 1.01–3.93) and adenoviruses (3.69, 1.29–10.56), and negatively with S. aureus carriage (0.42, 0.25–0.69). We observed a strong positive association between S. aureus and influenza viruses (4.87, 1.59–14.89). In addition, human rhinoviruses and enteroviruses were positively correlated (2.40, 1.66–3.47), as were enteroviruses and human bocavirus, WU polyomavirus, parainfluenza viruses, and human parechovirus. A negative association was observed between human rhinoviruses and coronaviruses. CONCLUSIONS/SIGNIFICANCE: Our data revealed high viral and bacterial prevalence rates and distinct bacterial-bacterial, viral-bacterial and viral-viral associations in healthy children, hinting towards the complexity and potential dynamics of microbial communities in the upper respiratory tract. This warrants careful consideration when associating microbial presence with specific respiratory diseases.",2012 Oct 17,"['van den Bergh, Menno R.', 'Biesbroek, Giske', 'Rossen, John W. A.', 'de Steenhuijsen Piters, Wouter A. A.', 'Bosch, Astrid A. T. M.', 'van Gils, Elske J. M.', 'Wang, Xinhui', 'Boonacker, Chantal W. B.', 'Veenhoven, Reinier H.', 'Bruin, Jacob P.', 'Bogaert, Debby', 'Sanders, Elisabeth A. M.']",PLoS One,,,False
9e8a907fcd9c6de7e99c2162e165079936e5d7f4,PMC,Associations between Pathogens in the Upper Respiratory Tract of Young Children: Interplay between Viruses and Bacteria,http://dx.doi.org/10.1371/journal.pone.0047711,PMC3474735,23082199,CC BY,"BACKGROUND: High rates of potentially pathogenic bacteria and respiratory viruses can be detected in the upper respiratory tract of healthy children. Investigating presence of and associations between these pathogens in healthy individuals is still a rather unexplored field of research, but may have implications for interpreting findings during disease. METHODOLOGY/PRINCIPAL FINDINGS: We selected 986 nasopharyngeal samples from 433 6- to 24-month-old healthy children that had participated in a randomized controlled trial. We determined the presence of 20 common respiratory viruses using real-time PCR. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus were identified by conventional culture methods. Information on risk factors was obtained by questionnaires. We performed multivariate logistic regression analyses followed by partial correlation analysis to identify the overall pattern of associations. S. pneumoniae colonization was positively associated with the presence of H. influenzae (adjusted odds ratio 1.60, 95% confidence interval 1.18–2.16), M. catarrhalis (1.78, 1.29–2.47), human rhinoviruses (1.63, 1.19–2.22) and enteroviruses (1.97, 1.26–3.10), and negatively associated with S. aureus presence (0.59, 0.35–0.98). H. influenzae was positively associated with human rhinoviruses (1.63, 1.22–2.18) and respiratory syncytial viruses (2.78, 1.06–7.28). M. catarrhalis colonization was positively associated with coronaviruses (1.99, 1.01–3.93) and adenoviruses (3.69, 1.29–10.56), and negatively with S. aureus carriage (0.42, 0.25–0.69). We observed a strong positive association between S. aureus and influenza viruses (4.87, 1.59–14.89). In addition, human rhinoviruses and enteroviruses were positively correlated (2.40, 1.66–3.47), as were enteroviruses and human bocavirus, WU polyomavirus, parainfluenza viruses, and human parechovirus. A negative association was observed between human rhinoviruses and coronaviruses. CONCLUSIONS/SIGNIFICANCE: Our data revealed high viral and bacterial prevalence rates and distinct bacterial-bacterial, viral-bacterial and viral-viral associations in healthy children, hinting towards the complexity and potential dynamics of microbial communities in the upper respiratory tract. This warrants careful consideration when associating microbial presence with specific respiratory diseases.",2012 Oct 17,"['van den Bergh, Menno R.', 'Biesbroek, Giske', 'Rossen, John W. A.', 'de Steenhuijsen Piters, Wouter A. A.', 'Bosch, Astrid A. T. M.', 'van Gils, Elske J. M.', 'Wang, Xinhui', 'Boonacker, Chantal W. B.', 'Veenhoven, Reinier H.', 'Bruin, Jacob P.', 'Bogaert, Debby', 'Sanders, Elisabeth A. M.']",PLoS One,,,False
e2eb9193178fb904a4a5c884b692c82ffc1eca43,PMC,CD200R1 Supports HSV-1 Viral Replication and Licenses Pro-Inflammatory Signaling Functions of TLR2,http://dx.doi.org/10.1371/journal.pone.0047740,PMC3474780,23082204,CC BY,"The CD200R1:CD200 axis is traditionally considered to limit tissue inflammation by down-regulating pro-inflammatory signaling in myeloid cells bearing the receptor. We generated CD200R1(−/−) mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1) infection. CD200R1(−/−) peritoneal macrophages demonstrated a 70–75% decrease in the generation of IL-6 and CCL5 (Rantes) in response to the TLR2 agonist Pam(2)CSK(4) and to HSV-1. CD200R1(−/−) macrophages could neither up-regulate the expression of TLR2, nor assemble a functional inflammasome in response to HSV-1. CD200R1(−/−) mice were protected from HSV-1 infection and exhibited dysfunctional TLR2 signaling. Finally, both CD200R1(−/−) mice and CD200R1(−/−) fibroblasts and macrophages showed a markedly reduced ability to support HSV-1 replication. In summary, our data demonstrate an unanticipated and novel requirement for CD200R1 in “licensing” pro-inflammatory functions of TLR2 and in limiting viral replication that are supported by ex vivo and in vivo evidence.",2012 Oct 17,"['Soberman, Roy J.', 'MacKay, Christopher R.', 'Vaine, Christine A.', 'Ryan, Glennice Bowen', 'Cerny, Anna M.', 'Thompson, Mikayla R.', 'Nikolic, Boris', 'Primo, Valeria', 'Christmas, Peter', 'Sheiffele, Paul', 'Aronov, Lisa', 'Knipe, David M.', 'Kurt-Jones, Evelyn A.']",PLoS One,,,True
6040c5668ac30592d68f281e5ecf313060b63d8c,PMC,CD200R1 Supports HSV-1 Viral Replication and Licenses Pro-Inflammatory Signaling Functions of TLR2,http://dx.doi.org/10.1371/journal.pone.0047740,PMC3474780,23082204,CC BY,"The CD200R1:CD200 axis is traditionally considered to limit tissue inflammation by down-regulating pro-inflammatory signaling in myeloid cells bearing the receptor. We generated CD200R1(−/−) mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1) infection. CD200R1(−/−) peritoneal macrophages demonstrated a 70–75% decrease in the generation of IL-6 and CCL5 (Rantes) in response to the TLR2 agonist Pam(2)CSK(4) and to HSV-1. CD200R1(−/−) macrophages could neither up-regulate the expression of TLR2, nor assemble a functional inflammasome in response to HSV-1. CD200R1(−/−) mice were protected from HSV-1 infection and exhibited dysfunctional TLR2 signaling. Finally, both CD200R1(−/−) mice and CD200R1(−/−) fibroblasts and macrophages showed a markedly reduced ability to support HSV-1 replication. In summary, our data demonstrate an unanticipated and novel requirement for CD200R1 in “licensing” pro-inflammatory functions of TLR2 and in limiting viral replication that are supported by ex vivo and in vivo evidence.",2012 Oct 17,"['Soberman, Roy J.', 'MacKay, Christopher R.', 'Vaine, Christine A.', 'Ryan, Glennice Bowen', 'Cerny, Anna M.', 'Thompson, Mikayla R.', 'Nikolic, Boris', 'Primo, Valeria', 'Christmas, Peter', 'Sheiffele, Paul', 'Aronov, Lisa', 'Knipe, David M.', 'Kurt-Jones, Evelyn A.']",PLoS One,,,False
5e1989bee9ae95c79dea0e12d9f455cb1d2b61d5,PMC,Critical COPD respiratory illness is linked to increased transcriptomic activity of neutrophil proteases genes,http://dx.doi.org/10.1186/1756-0500-5-401,PMC3475085,22852767,CC BY,"BACKGROUND: Gene expression profiling (GEP) in cells obtained from peripheral blood has shown that this is a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases. While there is limited literature available on gene expression markers associated with Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated with critical respiratory illness in this disease is not known at the present moment. FINDINGS: By using Agilent microarray chips, we have profiled gene expression signatures in the whole blood of 28 COPD patients hospitalized with different degrees of respiratory compromise.12 of them needed of admission to the ICU, whilst 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0 software was used for performing statistical comparisons of transcript levels between ICU and non-ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to select, annotate and visualize genes by function and pathway (gene ontology). T-test showed evidence of 1501 genes differentially expressed between ICU and non-ICU patients. IPA and KEGG analysis of the most representative biological functions revealed that ICU patients had increased levels of neutrophil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], and [bactericidal/permeability-increasing protein (BPI)] the most representative ones. Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage. This “neutrophil signature” was paralleled by the necessity of advanced respiratory and vital support, and the presence of bacterial infection. CONCLUSION: Study of transcriptomic signatures in blood suggests an essential role of neutrophil proteases in COPD patients with critical respiratory illness. Measurement and modulation of the expression of these genes could present an option for clinical monitoring and treatment of severe COPD exacerbations.",2012 Aug 2,"['Almansa, Raquel', 'Socias, Lorenzo', 'Sanchez-Garcia, Monica', 'Martín-Loeches, Ignacio', 'del Olmo, Milagros', 'Andaluz-Ojeda, David', 'Bobillo, Felipe', 'Rico, Lucia', 'Herrero, Agueda', 'Roig, Vicente', 'San-Jose, C Alicia', 'Rosich, Sara', 'Barbado, Julia', 'Disdier, Carlos', 'de Lejarazu, Raúl Ortiz', 'Gallegos, Maria C', 'Fernandez, Victoria', 'Bermejo-Martin, Jesus F']",BMC Res Notes,,,True
1808454d2e8c7d1088e58a5e3a52111a8c507554,PMC,"Epidemiological, molecular and clinical features of Enterovirus 109 infection in children and in adult stem cell transplant recipients",http://dx.doi.org/10.1186/1743-422X-9-183,PMC3477084,22947270,CC BY,"BACKGROUND: A novel human enterovirus (HEV) type within the species HEV-C, named EV109, was discovered from cases of respiratory illness in Nicaragua in September 2010. The aim of this study, was to retrospectively examine the presence and the role of EV109 in respiratory samples from two patients populations; infants below the age of 2 years, hospitalized for acute respiratory diseases (ARDs) and adult hematopoietic stem cell transplantation recipients. RESULTS: A total of 1149 nasopharingeal aspirates were collected and tested for the presence of EV109 by reverse transcription-PCR (RT-PCR). In positive samples, the presence of the most common respiratory viruses was also assayed and clinical symptoms were evaluated. Samples from 2 of the 974 infants tested positive for EV109 RNA (0.2%) and belonged to patients with lower ARDs; co-infection with other viral pathogens under study was observed in both cases. In transplant recipients, one out of the 175 samples analyzed, from a patients with upper respiratory simptoms tested positive for HEV 109 in the absence of co-infecting viruses. Sequence analysis of amplified EV109 genomic regions, showed only a few nucleotide differences when compared with the Nicaraguan strains. CONCLUSIONS: Overall these results indicate that HEV109 variants have circulated and differentiated in different lineages worldwide. Although more cases and larger studies are needed, HEV109 infection may be associated to ARDs both in infants and in hematopoietic stem cell transplantation recipients. If these preliminary observations will be confirmed, improved molecular methods with a wider panel of potential pathogens will be useful for monitoring these categories of patients.",2012 Sep 4,"['Debiaggi, Maurizia', 'Ceresola, Elisa Rita', 'Sampaolo, Michela', 'Alessandrino, Emilio Paolo', 'Brerra, Roberto', 'Piazza, Aurora', 'Clementi, Massimo', 'Canducci, Filippo']",Virol J,,,True
6177fd107242a0dbf2cfdd0d617e6a384dba6eaa,PMC,Understanding Viral Transmission Behavior via Protein Intrinsic Disorder Prediction: Coronaviruses,http://dx.doi.org/10.1155/2012/738590,PMC3477565,23097708,CC BY,"Besides being a common threat to farm animals and poultry, coronavirus (CoV) was responsible for the human severe acute respiratory syndrome (SARS) epidemic in 2002–4. However, many aspects of CoV behavior, including modes of its transmission, are yet to be fully understood. We show that the amount and the peculiarities of distribution of the protein intrinsic disorder in the viral shell can be used for the efficient analysis of the behavior and transmission modes of CoV. The proposed model allows categorization of the various CoVs by the peculiarities of disorder distribution in their membrane (M) and nucleocapsid (N). This categorization enables quick identification of viruses with similar behaviors in transmission, regardless of genetic proximity. Based on this analysis, an empirical model for predicting the viral transmission behavior is developed. This model is able to explain some behavioral aspects of important coronaviruses that previously were not fully understood. The new predictor can be a useful tool for better epidemiological, clinical, and structural understanding of behavior of both newly emerging viruses and viruses that have been known for a long time. A potentially new vaccine strategy could involve searches for viral strains that are characterized by the evolutionary misfit between the peculiarities of the disorder distribution in their shells and their behavior.",2012 Oct 14,"['Goh, Gerard Kian-Meng', 'Dunker, A. Keith', 'Uversky, Vladimir N.']",J Pathog,,,True
232dc9f3baa927facbe91722ae717e0738a73981,PMC,Genome-wide expression profiling shows transcriptional reprogramming in Fusarium graminearum by Fusarium graminearum virus 1-DK21 infection,http://dx.doi.org/10.1186/1471-2164-13-173,PMC3478160,22559730,CC BY,"BACKGROUND: Fusarium graminearum virus 1 strain-DK21 (FgV1-DK21) is a mycovirus that confers hypovirulence to F. graminearum, which is the primary phytopathogenic fungus that causes Fusarium head blight (FHB) disease in many cereals. Understanding the interaction between mycoviruses and plant pathogenic fungi is necessary for preventing damage caused by F. graminearum. Therefore, we investigated important cellular regulatory processes in a host containing FgV1-DK21 as compared to an uninfected parent using a transcriptional approach. RESULTS: Using a 3′-tiling microarray covering all known F. graminearum genes, we carried out genome-wide expression analyses of F. graminearum at two different time points. At the early point of growth of an infected strain as compared to an uninfected strain, genes associated with protein synthesis, including ribosome assembly, nucleolus, and ribosomal RNA processing, were significantly up-regulated. In addition, genes required for transcription and signal transduction, including fungal-specific transcription factors and cAMP signaling, respectively, were actively up-regulated. In contrast, genes involved in various metabolic pathways, particularly in producing carboxylic acids, aromatic amino acids, nitrogen compounds, and polyamines, showed dramatic down-regulation at the early time point. Moreover, genes associated with transport systems localizing to transmembranes were down-regulated at both time points. CONCLUSION: This is the first report of global change in the prominent cellular pathways in the Fusarium host containing FgV1-DK21. The significant increase in transcripts for transcription and translation machinery in fungal host cells seems to be related to virus replication. In addition, significant down-regulation of genes required for metabolism and transporting systems in a fungal host containing the virus appears to be related to the host defense mechanism and fungal virulence. Taken together, our data aid in the understanding of how FgV1-DK21 regulates the transcriptional reprogramming of F. graminearum.",2012 May 6,"['Cho, Won Kyong', 'Yu, Jisuk', 'Lee, Kyung-Mi', 'Son, Moonil', 'Min, Kyunghun', 'Lee, Yin-Won', 'Kim, Kook-Hyung']",BMC Genomics,,,True
4fce2cc8270c75b0db8e7679d63b40abc5470f6b,PMC,18β-glycyrrhetinic acid inhibits rotavirus replication in culture,http://dx.doi.org/10.1186/1743-422X-9-96,PMC3478227,22616823,CC BY,"BACKGROUND: Glycyrrhizin (GA) and primary metabolite 18β-glycyrrhetinic acid (GRA) are pharmacologically active components of the medicinal licorice root, and both have been shown to have antiviral and immunomodulatory properties. Although these properties are well established, the mechanisms of action are not completely understood. In this study, GA and GRA were tested for the ability to inhibit rotavirus replication in cell culture, toward a long term goal of discovering natural compounds that may complement existing vaccines. METHODS: Epithelial cells were treated with GA or GRA various times pre- or post-infection and virus yields were measured by immunofluorescent focus assay. Levels of viral proteins VP2, VP6, and NSP2 in GRA treated cells were measured by immunoblot to determine if there was an effect of GRA treatment on the accumulation of viral protein. RESULTS: GRA treatment reduced rotavirus yields by 99% when added to infected cultures post-- virus adsorption, whereas virus yields in GA treated cultures were similar to mock treated controls. Time of addition experiments indicated that GRA-mediated replication inhibition likely occurs at a step or steps subsequent to virus entry. The amounts of VP2, VP6 and NSP2 were substantially reduced when GRA was added to cultures up to two hours post-entry. CONCLUSIONS: GRA, but not GA, has significant antiviral activity against rotavirus replication in vitro, and studies to determine whether GRA attenuates rotavirus replication in vivo are underway.",2012 May 22,"['Hardy, Michele E', 'Hendricks, Jay M', 'Paulson, Jeana M', 'Faunce, Nicholas R']",Virol J,,,True
8a6f367d81903273daadb6e142149f2feff80d6e,PMC,"Interplay of foot-and-mouth disease virus, antibodies and plasmacytoid dendritic cells: virus opsonization under non-neutralizing conditions results in enhanced interferon-alpha responses",http://dx.doi.org/10.1186/1297-9716-43-64,PMC3479418,22934974,CC BY,"Foot-and-mouth disease virus (FMDV) is a highly infectious member of the Picornaviridae inducing an acute disease of cloven-hoofed species. Vaccine-induced immune protection correlates with the presence of high levels of neutralizing antibodies but also opsonising antibodies have been proposed as an important mechanism of the immune response contributing to virus clearance by macrophages and leading to the production of type-I interferon (IFN) by plasmacytoid dendritic cells (pDC). The present study demonstrates that the opsonising antibody titres mediating enhanced IFN-α responses in pDC were similar to neutralizing titres, when antigenically related viruses from the same serotype were employed. However, sera cross-reacted also with non-neutralized isolates of multiple serotypes, when tested in this assay. Both uncomplexed virus and immune complexed virus stimulated pDC via Toll-like receptor 7. An additional finding of potential importance for strain-specific differences in virulence and/or immunogenicity was that pDC activation by FMDV strongly differed between viral isolates. Altogether, our results indicate that opsonising antibodies can have a broader reactivity than neutralizing antibodies and may contribute to antiviral responses induced against antigenically distant viruses.",2012 Aug 30,"['Lannes, Nils', 'Python, Sylvie', 'Summerfield, Artur']",Vet Res,,,True
8b13309e21cd13564b46ef8d78bf927cf558f6f1,PMC,A Three-Dimensional Comparison of Tick-Borne Flavivirus Infection in Mammalian and Tick Cell Lines,http://dx.doi.org/10.1371/journal.pone.0047912,PMC3480448,23112871,CC0,"Tick-borne flaviviruses (TBFV) are sustained in nature through cycling between mammalian and tick hosts. In this study, we used African green monkey kidney cells (Vero) and Ixodes scapularis tick cells (ISE6) to compare virus-induced changes in mammalian and arthropod cells. Using confocal microscopy, transmission electron microscopy (TEM), and electron tomography (ET), we examined viral protein distribution and the ultrastructural changes that occur during TBFV infection. Within host cells, flaviviruses cause complex rearrangement of cellular membranes for the purpose of virus replication. Virus infection was accompanied by a marked expansion in endoplasmic reticulum (ER) staining and markers for TBFV replication were localized mainly to the ER in both cell lines. TEM of Vero cells showed membrane-bound vesicles enclosed in a network of dilated, anastomosing ER cisternae. Virions were seen within the ER and were sometimes in paracrystalline arrays. Tubular structures or elongated vesicles were occasionally noted. In acutely and persistently infected ISE6 cells, membrane proliferation and vesicles were also noted; however, the extent of membrane expansion and the abundance of vesicles were lower and no viral particles were observed. Tubular profiles were far more prevalent in persistently infected ISE6 cells than in acutely infected cells. By ET, tubular profiles, in persistently infected tick cells, had a cross-sectional diameter of 60–100 nm, reached up to 800 nm in length, were closed at the ends, and were often arranged in fascicle-like bundles, shrouded with ER membrane. Our experiments provide analysis of viral protein localization within the context of both mammalian and arthropod cell lines as well as both acute and persistent arthropod cell infection. Additionally, we show for the first time 3D flavivirus infection in a vector cell line and the first ET of persistent flavivirus infection.",2012 Oct 24,"['Offerdahl, Danielle K.', 'Dorward, David W.', 'Hansen, Bryan T.', 'Bloom, Marshall E.']",PLoS One,,,True
ce05a808109c6307485aeda93945cd3b0e536623,PMC,"SEED Servers: High-Performance Access to the SEED Genomes, Annotations, and Metabolic Models",http://dx.doi.org/10.1371/journal.pone.0048053,PMC3480482,23110173,CC0,"The remarkable advance in sequencing technology and the rising interest in medical and environmental microbiology, biotechnology, and synthetic biology resulted in a deluge of published microbial genomes. Yet, genome annotation, comparison, and modeling remain a major bottleneck to the translation of sequence information into biological knowledge, hence computational analysis tools are continuously being developed for rapid genome annotation and interpretation. Among the earliest, most comprehensive resources for prokaryotic genome analysis, the SEED project, initiated in 2003 as an integration of genomic data and analysis tools, now contains >5,000 complete genomes, a constantly updated set of curated annotations embodied in a large and growing collection of encoded subsystems, a derived set of protein families, and hundreds of genome-scale metabolic models. Until recently, however, maintaining current copies of the SEED code and data at remote locations has been a pressing issue. To allow high-performance remote access to the SEED database, we developed the SEED Servers (http://www.theseed.org/servers): four network-based servers intended to expose the data in the underlying relational database, support basic annotation services, offer programmatic access to the capabilities of the RAST annotation server, and provide access to a growing collection of metabolic models that support flux balance analysis. The SEED servers offer open access to regularly updated data, the ability to annotate prokaryotic genomes, the ability to create metabolic reconstructions and detailed models of metabolism, and access to hundreds of existing metabolic models. This work offers and supports a framework upon which other groups can build independent research efforts. Large integrations of genomic data represent one of the major intellectual resources driving research in biology, and programmatic access to the SEED data will provide significant utility to a broad collection of potential users.",2012 Oct 24,"['Aziz, Ramy K.', 'Devoid, Scott', 'Disz, Terrence', 'Edwards, Robert A.', 'Henry, Christopher S.', 'Olsen, Gary J.', 'Olson, Robert', 'Overbeek, Ross', 'Parrello, Bruce', 'Pusch, Gordon D.', 'Stevens, Rick L.', 'Vonstein, Veronika', 'Xia, Fangfang']",PLoS One,,,True
15029a39f0a27d1bbccb6fed1793ea25700d9e57,PMC,"SEED Servers: High-Performance Access to the SEED Genomes, Annotations, and Metabolic Models",http://dx.doi.org/10.1371/journal.pone.0048053,PMC3480482,23110173,CC0,"The remarkable advance in sequencing technology and the rising interest in medical and environmental microbiology, biotechnology, and synthetic biology resulted in a deluge of published microbial genomes. Yet, genome annotation, comparison, and modeling remain a major bottleneck to the translation of sequence information into biological knowledge, hence computational analysis tools are continuously being developed for rapid genome annotation and interpretation. Among the earliest, most comprehensive resources for prokaryotic genome analysis, the SEED project, initiated in 2003 as an integration of genomic data and analysis tools, now contains >5,000 complete genomes, a constantly updated set of curated annotations embodied in a large and growing collection of encoded subsystems, a derived set of protein families, and hundreds of genome-scale metabolic models. Until recently, however, maintaining current copies of the SEED code and data at remote locations has been a pressing issue. To allow high-performance remote access to the SEED database, we developed the SEED Servers (http://www.theseed.org/servers): four network-based servers intended to expose the data in the underlying relational database, support basic annotation services, offer programmatic access to the capabilities of the RAST annotation server, and provide access to a growing collection of metabolic models that support flux balance analysis. The SEED servers offer open access to regularly updated data, the ability to annotate prokaryotic genomes, the ability to create metabolic reconstructions and detailed models of metabolism, and access to hundreds of existing metabolic models. This work offers and supports a framework upon which other groups can build independent research efforts. Large integrations of genomic data represent one of the major intellectual resources driving research in biology, and programmatic access to the SEED data will provide significant utility to a broad collection of potential users.",2012 Oct 24,"['Aziz, Ramy K.', 'Devoid, Scott', 'Disz, Terrence', 'Edwards, Robert A.', 'Henry, Christopher S.', 'Olsen, Gary J.', 'Olson, Robert', 'Overbeek, Ross', 'Parrello, Bruce', 'Pusch, Gordon D.', 'Stevens, Rick L.', 'Vonstein, Veronika', 'Xia, Fangfang']",PLoS One,,,True
630a27f09c2caab65471e97cf1d538d364a2498a,PMC,"First report of Toxoplasma gondii seroprevalence in peafowls in Yunnan Province, Southwestern China",http://dx.doi.org/10.1186/1756-3305-5-205,PMC3480843,22992281,CC BY,"BACKGROUND: Toxoplasma gondii is an intracellular protozoan parasite infecting almost all warm-blooded animals, including birds, with a worldwide distribution. Surveys of T. gondii infection in wild birds have been reported extensively in the world, but little is known of T. gondii infection in peafowls worldwide. This study was performed to determine the seroprevalence of T. gondii infection in peafowls in Yunnan Province, southwestern China. METHODS: Sera from 277 peafowls, including 272 blue peafowls (Pavo cristatus) and 5 green peafowls (Pavo muticus) originated from two geographic areas in Yunnan Province were assayed for T. gondii antibodies using the modified agglutination test (MAT). RESULTS: Specific T. gondii antibodies were detected in 35 of 277 (12.64%) peafowls (MAT titer ≥ 1:5). Seropositive birds were found in both species, 33 in 272 blue peafowls and 2 in 5 green peafowls. There was no significant difference in T. gondii seroprevalence between the adolescent birds (6.74%) and the adult birds (6.67%) (P > 0.05). The geographical origins of peafowls was found to be highly associated with T. gondii infection in the present study, a statistically significant difference in T. gondii seropositivity was observed between peafowls from Kunming (31.08%) and those from Xishuangbanna Dai Autonomous Prefecture (5.91%) (OR = 10.956, 95% CI = 1.632-73.545, P = 0.014). Statistical analyses showed that there were no significant interactions between ages and geographical origins of peafowls (P > 0.05). CONCLUSIONS: The results of the present survey indicated that infection of peafowls with T. gondii is widespread in Yunnan Province, which has significant public health concerns and implications for prevention and control of toxoplamosis in this province. To our knowledge, this is the first seroprevalence report of T. gondii infection in China’s southwestern Yunnan Province.",2012 Sep 19,"['Tian, Yi-Ming', 'Dai, Fei-Yan', 'Huang, Si-Yang', 'Deng, Zu-Hong', 'Duan, Gang', 'Zhou, Dong-Hui', 'Yang, Jian-Fa', 'Weng, Ya-Biao', 'Zhu, Xing-Quan', 'Zou, Feng-Cai']",Parasit Vectors,,,True
69d2e69e949dab8909be8c7b764a0d5469546b31,PMC,Evaluation of reference genes for real-time quantitative PCR studies in Candida glabrata following azole treatment,http://dx.doi.org/10.1186/1471-2199-13-22,PMC3482582,22747760,CC BY,"BACKGROUND: The selection of stable and suitable reference genes for real-time quantitative PCR (RT-qPCR) is a crucial prerequisite for reliable gene expression analysis under different experimental conditions. The present study aimed to identify reference genes as internal controls for gene expression studies by RT-qPCR in azole-stimulated Candida glabrata. RESULTS: The expression stability of 16 reference genes under fluconazole stress was evaluated using fold change and standard deviation computations with the hkgFinder tool. Our data revealed that the mRNA expression levels of three ribosomal RNAs (RDN5.8, RDN18, and RDN25) remained stable in response to fluconazole, while PGK1, UBC7, and UBC13 mRNAs showed only approximately 2.9-, 3.0-, and 2.5-fold induction by azole, respectively. By contrast, mRNA levels of the other 10 reference genes (ACT1, EF1α, GAPDH, PPIA, RPL2A, RPL10, RPL13A, SDHA, TUB1, and UBC4) were dramatically increased in C. glabrata following antifungal treatment, exhibiting changes ranging from 4.5- to 32.7-fold. We also assessed the expression stability of these reference genes using the 2(-ΔΔCT) method and three other software packages. The stability rankings of the reference genes by geNorm and the 2(-ΔΔCT) method were identical to those by hkgFinder, whereas the stability rankings by BestKeeper and NormFinder were notably different. We then validated the suitability of six candidate reference genes (ACT1, PGK1, RDN5.8, RDN18, UBC7, and UBC13) as internal controls for ten target genes in this system using the comparative C(T) method. Our validation experiments passed for all six reference genes analyzed except RDN18, where the amplification efficiency of RDN18 was different from that of the ten target genes. Finally, we demonstrated that the relative quantification of target gene expression varied according to the endogenous control used, highlighting the importance of the choice of internal controls in such experiments. CONCLUSIONS: We recommend the use of RDN5.8, UBC13, and PGK1 alone or the combination of RDN5.8 plus UBC13 or PGK1 as reference genes for RT-qPCR analysis of gene expression in C. glabrata following azole treatment. In contrast, we show that ACT1 and other commonly used reference genes (GAPDH, PPIA, RPL13A, TUB1, etc.) were not validated as good internal controls in the current model.",2012 Jun 29,"['Li, Qingdi Quentin', 'Skinner, Jeff', 'Bennett, John E']",BMC Mol Biol,,,True
02a9fd5f564cb3a5b6b1fdbcd9df585b8e24a2de,PMC,Performance Evaluation of the Maxwell 16 System for Extraction of Influenza Virus RNA from Diverse Samples,http://dx.doi.org/10.1371/journal.pone.0048094,PMC3483271,23144730,CC BY,"This study evaluated the performance of the Maxwell 16 System (Promega) for extraction of influenza virus (flu-v) RNA from diverse samples compared to a classical manual method (QIAamp Kit, QIAGEN). Following extraction by the two methods, all samples were analyzed by Real-time RT-PCR. Results revealed that the use of the standard Maxwell 16 protocol (Maxwell 16-S) resulted in good linearity and precision across a wide concentration range and higher sensitivity of detection from flu-v stock suspensions than the manual method. Compared with the latter method, Maxwell 16-S extracted RNA more efficiently (higher RNA yield and/or fewer PCR inhibitors) from throat swabs and bronchoalveolar lavage fluids, while both methods performed comparably on fecal samples from human and poultry in terms of overall threshold cycle values and detection rates although the Maxwell 16-S co-purified more inhibitors from fecal samples. The capacity of this system to remove inhibitors from fecal matrix was improved by using a modified Maxwell 16 protocol with a reduced sample input, which eliminated all false-negatives produced by the Maxwell 16-S. These findings suggest that the Maxwell 16 System is suitable for RNA extraction from multiple-source samples for diagnosis of influenza and viral load determination and that a proper reduction in starting sample volume may improve the detection of flu-v from complex matrices such as feces. Additionally, this system allows flexible sample throughput and labor-saving sample processing with little or no risk of cross-contamination.",2012 Oct 29,"['Liu, Hongbo', 'Gan, Yan', 'Yang, Bo', 'Weng, Hui', 'Huang, Chunmei', 'Yang, Daofeng', 'Lei, Ping', 'Shen, Guanxin']",PLoS One,,,True
c9fca01d18bac485ae1c5257a712c516aeea8408,PMC,Discovery and Targeted LC-MS/MS of Purified Polerovirus Reveals Differences in the Virus-Host Interactome Associated with Altered Aphid Transmission,http://dx.doi.org/10.1371/journal.pone.0048177,PMC3484124,23118947,CC0,"Circulative transmission of viruses in the Luteoviridae, such as cereal yellow dwarf virus (CYDV), requires a series of precisely orchestrated interactions between virus, plant, and aphid proteins. Natural selection has favored these viruses to be retained in the phloem to facilitate acquisition and transmission by aphids. We show that treatment of infected oat tissue homogenate with sodium sulfite reduces transmission of the purified virus by aphids. Transmission electron microscopy data indicated no gross change in virion morphology due to treatments. However, treated virions were not acquired by aphids through the hindgut epithelial cells and were not transmitted when injected directly into the hemocoel. Analysis of virus preparations using nanoflow liquid chromatography coupled to tandem mass spectrometry revealed a number of host plant proteins co-purifying with viruses, some of which were lost following sodium sulfite treatment. Using targeted mass spectrometry, we show data suggesting that several of the virus-associated host plant proteins accumulated to higher levels in aphids that were fed on CYDV-infected plants compared to healthy plants. We propose two hypotheses to explain these observations, and these are not mutually exclusive: (a) that sodium sulfite treatment disrupts critical virion-host protein interactions required for aphid transmission, or (b) that host infection with CYDV modulates phloem protein expression in a way that is favorable for virus uptake by aphids. Importantly, the genes coding for the plant proteins associated with virus may be examined as targets in breeding cereal crops for new modes of virus resistance that disrupt phloem-virus or aphid-virus interactions.",2012 Oct 30,"['Cilia, Michelle', 'Peter, Kari A.', 'Bereman, Michael S.', 'Howe, Kevin', 'Fish, Tara', 'Smith, Dawn', 'Gildow, Fredrick', 'MacCoss, Michael J.', 'Thannhauser, Theodore W.', 'Gray, Stewart M.']",PLoS One,,,True
8a71eeb8c75ab05167e5d0a6ac12e6f8d6eb61fd,PMC,Discovery and Targeted LC-MS/MS of Purified Polerovirus Reveals Differences in the Virus-Host Interactome Associated with Altered Aphid Transmission,http://dx.doi.org/10.1371/journal.pone.0048177,PMC3484124,23118947,CC0,"Circulative transmission of viruses in the Luteoviridae, such as cereal yellow dwarf virus (CYDV), requires a series of precisely orchestrated interactions between virus, plant, and aphid proteins. Natural selection has favored these viruses to be retained in the phloem to facilitate acquisition and transmission by aphids. We show that treatment of infected oat tissue homogenate with sodium sulfite reduces transmission of the purified virus by aphids. Transmission electron microscopy data indicated no gross change in virion morphology due to treatments. However, treated virions were not acquired by aphids through the hindgut epithelial cells and were not transmitted when injected directly into the hemocoel. Analysis of virus preparations using nanoflow liquid chromatography coupled to tandem mass spectrometry revealed a number of host plant proteins co-purifying with viruses, some of which were lost following sodium sulfite treatment. Using targeted mass spectrometry, we show data suggesting that several of the virus-associated host plant proteins accumulated to higher levels in aphids that were fed on CYDV-infected plants compared to healthy plants. We propose two hypotheses to explain these observations, and these are not mutually exclusive: (a) that sodium sulfite treatment disrupts critical virion-host protein interactions required for aphid transmission, or (b) that host infection with CYDV modulates phloem protein expression in a way that is favorable for virus uptake by aphids. Importantly, the genes coding for the plant proteins associated with virus may be examined as targets in breeding cereal crops for new modes of virus resistance that disrupt phloem-virus or aphid-virus interactions.",2012 Oct 30,"['Cilia, Michelle', 'Peter, Kari A.', 'Bereman, Michael S.', 'Howe, Kevin', 'Fish, Tara', 'Smith, Dawn', 'Gildow, Fredrick', 'MacCoss, Michael J.', 'Thannhauser, Theodore W.', 'Gray, Stewart M.']",PLoS One,,,False
99bef7780df3f4c309e62e9aa33ec62753052623,PMC,Discovery and Targeted LC-MS/MS of Purified Polerovirus Reveals Differences in the Virus-Host Interactome Associated with Altered Aphid Transmission,http://dx.doi.org/10.1371/journal.pone.0048177,PMC3484124,23118947,CC0,"Circulative transmission of viruses in the Luteoviridae, such as cereal yellow dwarf virus (CYDV), requires a series of precisely orchestrated interactions between virus, plant, and aphid proteins. Natural selection has favored these viruses to be retained in the phloem to facilitate acquisition and transmission by aphids. We show that treatment of infected oat tissue homogenate with sodium sulfite reduces transmission of the purified virus by aphids. Transmission electron microscopy data indicated no gross change in virion morphology due to treatments. However, treated virions were not acquired by aphids through the hindgut epithelial cells and were not transmitted when injected directly into the hemocoel. Analysis of virus preparations using nanoflow liquid chromatography coupled to tandem mass spectrometry revealed a number of host plant proteins co-purifying with viruses, some of which were lost following sodium sulfite treatment. Using targeted mass spectrometry, we show data suggesting that several of the virus-associated host plant proteins accumulated to higher levels in aphids that were fed on CYDV-infected plants compared to healthy plants. We propose two hypotheses to explain these observations, and these are not mutually exclusive: (a) that sodium sulfite treatment disrupts critical virion-host protein interactions required for aphid transmission, or (b) that host infection with CYDV modulates phloem protein expression in a way that is favorable for virus uptake by aphids. Importantly, the genes coding for the plant proteins associated with virus may be examined as targets in breeding cereal crops for new modes of virus resistance that disrupt phloem-virus or aphid-virus interactions.",2012 Oct 30,"['Cilia, Michelle', 'Peter, Kari A.', 'Bereman, Michael S.', 'Howe, Kevin', 'Fish, Tara', 'Smith, Dawn', 'Gildow, Fredrick', 'MacCoss, Michael J.', 'Thannhauser, Theodore W.', 'Gray, Stewart M.']",PLoS One,,,False
02fe68e2ba45e7f0c6f746d4b3db36f8f99ae4f5,PMC,Communicable disease control in China: From Mao to now,,PMC3484775,23198121,CC BY,"China’s progress on communicable disease control (CDC) in the 30 years after establishment of the People’s Republic in 1949 is widely regarded as remarkable. Life expectancy soared by around 30 years, infant mortality plummeted and smallpox, sexually transmitted diseases and many other infections were either eliminated or decreased massively in incidence, largely as a result of CDC. By the mid-1970s, China was already undergoing the epidemiologic transition, years ahead of other nations of similar economic status. These early successes can be attributed to population mobilization, mass campaigns and a focus on sanitation, hygiene, clean water and clean delivery, and occurred despite political instability and slow economic progress. The 10-year Cultural Revolution from 1966 brought many hardships, but also clinical care and continuing public health programs to the masses through community-funded medical schemes and the establishment of community-based health workers. These people-focused approaches broke down with China’s market reforms from 1980. Village doctors turned to private practice as community funding ceased, and the attention paid to rural public health declined. CDC relied on vertical programs, some of them successful (such as elimination of lymphatic filariasis and child immunisation), but others (such as control of schistosomiasis and tuberculosis) demonstrating only intermittent progress due to failed strategies or reliance on support by the poorest governments and health workers, who could not or would not collaborate. In addition, China’s laissez-faire approach to public health placed it at great risk, as evidenced by the outbreak in 2003 of the Severe Acute Respiratory Syndrome. Since then, major changes to disease reporting, the priority given to CDC including through major new domestic resources and reform of China’s health system offer encouragement for CDC. While decentralized funding and varying quality diagnosis, reporting and treatment of infectious diseases remain major challenges, national priority on CDC in China is high.",2011 Dec,"Hipgrave, David",J Glob Health,,,True
1d4793842e3eeae37f34abb1541b0cee61ff976d,PMC,"Mortality, Severe Acute Respiratory Infection, and Influenza-Like Illness Associated with Influenza A(H1N1)pdm09 in Argentina, 2009",http://dx.doi.org/10.1371/journal.pone.0047540,PMC3485247,23118877,CC0,"INTRODUCTION: While there is much information about the burden of influenza A(H1N1)pdm09 in North America, little data exist on its burden in South America. METHODS: During April to December 2009, we actively searched for persons with severe acute respiratory infection and influenza-like illness (ILI) in three sentinel cities. A proportion of case-patients provided swabs for influenza testing. We estimated the number of case-patients that would have tested positive for influenza by multiplying the number of untested case-patients by the proportion who tested positive. We estimated rates by dividing the estimated number of case-patients by the census population after adjusting for the proportion of case-patients with missing illness onset information and ILI case-patients who visited physicians multiple times for one illness event. RESULTS: We estimated that the influenza A(H1N1)pdm09 mortality rate per 100,000 person-years (py) ranged from 1.5 among persons aged 5–44 years to 5.6 among persons aged ≥65 years. A(H1N1)pdm09 hospitalization rates per 100,000 py ranged between 26.9 among children aged <5 years to 41.8 among persons aged ≥65 years. Influenza A(H1N1)pdm09 ILI rates per 100 py ranged between 1.6 among children aged <5 to 17.1 among persons aged 45–64 years. While 9 (53%) of 17 influenza A(H1N1)pdm09 decedents with available data had obesity and 7 (17%) of 40 had diabetes, less than 4% of surviving influenza A(H1N1)pdm09 case-patients had these pre-existing conditions (p≤0.001). CONCLUSION: Influenza A(H1N1)pdm09 caused a similar burden of disease in Argentina as in other countries. Such disease burden suggests the potential value of timely influenza vaccinations.",2012 Oct 31,"['Azziz-Baumgartner, Eduardo', 'Cabrera, Ana María', 'Chang, Loretta', 'Calli, Rogelio', 'Kusznierz, Gabriela', 'Baez, Clarisa', 'Yedlin, Pablo', 'Zamora, Ana María', 'Cuezzo, Romina', 'Sarrouf, Elena Beatriz', 'Uboldi, Andrea', 'Herrmann, Juan', 'Zerbini, Elsa', 'Uez, Osvaldo', 'Rico Cordeiro, Pedro Osvaldo', 'Chavez, Pollyanna', 'Han, George', 'Antman, Julián', 'Coronado, Fatima', 'Bresee, Joseph', 'Kosacoff, Marina', 'Widdowson, Marc-Alain', 'Echenique, Horacio']",PLoS One,,,True
f0fb3bbd96dad4c907c7fd456cd5783ed8fa7bd6,PMC,"C. difficile 630Δerm Spo0A Regulates Sporulation, but Does Not Contribute to Toxin Production, by Direct High-Affinity Binding to Target DNA",http://dx.doi.org/10.1371/journal.pone.0048608,PMC3485338,23119071,CC BY,"Clostridium difficile is a Gram positive, anaerobic bacterium that can form highly resistant endospores. The bacterium is the causative agent of C. difficile infection (CDI), for which the symptoms can range from a mild diarrhea to potentially fatal pseudomembranous colitis and toxic megacolon. Endospore formation in Firmicutes, including C. difficile, is governed by the key regulator for sporulation, Spo0A. In Bacillus subtilis, this transcription factor is also directly or indirectly involved in various other cellular processes. Here, we report that C. difficile Spo0A shows a high degree of similarity to the well characterized B. subtilis protein and recognizes a similar binding sequence. We find that the laboratory strain C. difficile 630Δerm contains an 18bp-duplication near the DNA-binding domain compared to its ancestral strain 630. In vitro binding assays using purified C-terminal DNA binding domain of the C. difficile Spo0A protein demonstrate direct binding to DNA upstream of spo0A and sigH, early sporulation genes and several other putative targets. In vitro binding assays suggest that the gene encoding the major clostridial toxin TcdB may be a direct target of Spo0A, but supernatant derived from a spo0A negative strain was no less toxic towards Vero cells than that obtained from a wild type strain, in contrast to previous reports. These results identify for the first time direct (putative) targets of the Spo0A protein in C. difficile and make a positive effect of Spo0A on production of the large clostridial toxins unlikely.",2012 Oct 31,"['Rosenbusch, Katharina E.', 'Bakker, Dennis', 'Kuijper, Ed J.', 'Smits, Wiep Klaas']",PLoS One,,,True
6ee4fb1e1119adb4af83b4f22b2b9142cb3c9c75,PMC,"C. difficile 630Δerm Spo0A Regulates Sporulation, but Does Not Contribute to Toxin Production, by Direct High-Affinity Binding to Target DNA",http://dx.doi.org/10.1371/journal.pone.0048608,PMC3485338,23119071,CC BY,"Clostridium difficile is a Gram positive, anaerobic bacterium that can form highly resistant endospores. The bacterium is the causative agent of C. difficile infection (CDI), for which the symptoms can range from a mild diarrhea to potentially fatal pseudomembranous colitis and toxic megacolon. Endospore formation in Firmicutes, including C. difficile, is governed by the key regulator for sporulation, Spo0A. In Bacillus subtilis, this transcription factor is also directly or indirectly involved in various other cellular processes. Here, we report that C. difficile Spo0A shows a high degree of similarity to the well characterized B. subtilis protein and recognizes a similar binding sequence. We find that the laboratory strain C. difficile 630Δerm contains an 18bp-duplication near the DNA-binding domain compared to its ancestral strain 630. In vitro binding assays using purified C-terminal DNA binding domain of the C. difficile Spo0A protein demonstrate direct binding to DNA upstream of spo0A and sigH, early sporulation genes and several other putative targets. In vitro binding assays suggest that the gene encoding the major clostridial toxin TcdB may be a direct target of Spo0A, but supernatant derived from a spo0A negative strain was no less toxic towards Vero cells than that obtained from a wild type strain, in contrast to previous reports. These results identify for the first time direct (putative) targets of the Spo0A protein in C. difficile and make a positive effect of Spo0A on production of the large clostridial toxins unlikely.",2012 Oct 31,"['Rosenbusch, Katharina E.', 'Bakker, Dennis', 'Kuijper, Ed J.', 'Smits, Wiep Klaas']",PLoS One,,,False
fcc1c06c4e3e68af5aba453e42a50bdf45f99ff0,PMC,"C. difficile 630Δerm Spo0A Regulates Sporulation, but Does Not Contribute to Toxin Production, by Direct High-Affinity Binding to Target DNA",http://dx.doi.org/10.1371/journal.pone.0048608,PMC3485338,23119071,CC BY,"Clostridium difficile is a Gram positive, anaerobic bacterium that can form highly resistant endospores. The bacterium is the causative agent of C. difficile infection (CDI), for which the symptoms can range from a mild diarrhea to potentially fatal pseudomembranous colitis and toxic megacolon. Endospore formation in Firmicutes, including C. difficile, is governed by the key regulator for sporulation, Spo0A. In Bacillus subtilis, this transcription factor is also directly or indirectly involved in various other cellular processes. Here, we report that C. difficile Spo0A shows a high degree of similarity to the well characterized B. subtilis protein and recognizes a similar binding sequence. We find that the laboratory strain C. difficile 630Δerm contains an 18bp-duplication near the DNA-binding domain compared to its ancestral strain 630. In vitro binding assays using purified C-terminal DNA binding domain of the C. difficile Spo0A protein demonstrate direct binding to DNA upstream of spo0A and sigH, early sporulation genes and several other putative targets. In vitro binding assays suggest that the gene encoding the major clostridial toxin TcdB may be a direct target of Spo0A, but supernatant derived from a spo0A negative strain was no less toxic towards Vero cells than that obtained from a wild type strain, in contrast to previous reports. These results identify for the first time direct (putative) targets of the Spo0A protein in C. difficile and make a positive effect of Spo0A on production of the large clostridial toxins unlikely.",2012 Oct 31,"['Rosenbusch, Katharina E.', 'Bakker, Dennis', 'Kuijper, Ed J.', 'Smits, Wiep Klaas']",PLoS One,,,False
23d8bce7be2d5afed730addd3b4531f1bc721da6,PMC,Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus,http://dx.doi.org/10.7554/eLife.00049,PMC3485615,23150796,CC BY,"Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157–165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV. DOI: http://dx.doi.org/10.7554/eLife.00049.001",2012 Nov 13,"['Yan, Huan', 'Zhong, Guocai', 'Xu, Guangwei', 'He, Wenhui', 'Jing, Zhiyi', 'Gao, Zhenchao', 'Huang, Yi', 'Qi, Yonghe', 'Peng, Bo', 'Wang, Haimin', 'Fu, Liran', 'Song, Mei', 'Chen, Pan', 'Gao, Wenqing', 'Ren, Bijie', 'Sun, Yinyan', 'Cai, Tao', 'Feng, Xiaofeng', 'Sui, Jianhua', 'Li, Wenhui']",eLife,,,True
dc5765fa88deec41d804ff9f32a2211b30a021d1,PMC,Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus,http://dx.doi.org/10.7554/eLife.00049,PMC3485615,23150796,CC BY,"Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157–165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV. DOI: http://dx.doi.org/10.7554/eLife.00049.001",2012 Nov 13,"['Yan, Huan', 'Zhong, Guocai', 'Xu, Guangwei', 'He, Wenhui', 'Jing, Zhiyi', 'Gao, Zhenchao', 'Huang, Yi', 'Qi, Yonghe', 'Peng, Bo', 'Wang, Haimin', 'Fu, Liran', 'Song, Mei', 'Chen, Pan', 'Gao, Wenqing', 'Ren, Bijie', 'Sun, Yinyan', 'Cai, Tao', 'Feng, Xiaofeng', 'Sui, Jianhua', 'Li, Wenhui']",eLife,,,False
b79088a023db89b12d5630e426661985aba3921e,PMC,The Evolutionary Pattern of Glycosylation Sites in Influenza Virus (H5N1) Hemagglutinin and Neuraminidase,http://dx.doi.org/10.1371/journal.pone.0049224,PMC3486865,23133677,CC BY,"Two glycoproteins, hemagglutinin (HA) and neuraminidase (NA), on the surface of influenza viruses play crucial roles in transfaunation, membrane fusion and the release of progeny virions. To explore the distribution of N-glycosylation sites (glycosites) in these two glycoproteins, we collected and aligned the amino acid sequences of all the HA and NA subtypes. Two glycosites were located at HA0 cleavage sites and fusion peptides and were strikingly conserved in all HA subtypes, while the remaining glycosites were unique to their subtypes. Two to four conserved glycosites were found in the stalk domain of NA, but these are affected by the deletion of specific stalk domain sequences. Another highly conserved glycosite appeared at the top center of tetrameric global domain, while the others glycosites were distributed around the global domain. Here we present a detailed investigation of the distribution and the evolutionary pattern of the glycosites in the envelope glycoproteins of IVs, and further focus on the H5N1 virus and conclude that the glycosites in H5N1 have become more complicated in HA and less influential in NA in the last five years.",2012 Nov 1,"['Chen, Wentian', 'Zhong, Yaogang', 'Qin, Yannan', 'Sun, Shisheng', 'Li, Zheng']",PLoS One,,,True
513cb067ae66876bca5e55d343cf196b8d5715e9,PMC,Niclosamide Is a Proton Carrier and Targets Acidic Endosomes with Broad Antiviral Effects,http://dx.doi.org/10.1371/journal.ppat.1002976,PMC3486884,23133371,CC BY,"Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV) and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H(+)-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.",2012 Oct 25,"['Jurgeit, Andreas', 'McDowell, Robert', 'Moese, Stefan', 'Meldrum, Eric', 'Schwendener, Reto', 'Greber, Urs F.']",PLoS Pathog,,,True
a50f3a7514dd9363e42a1eff725a7eb3e49b6ed2,PMC,Niclosamide Is a Proton Carrier and Targets Acidic Endosomes with Broad Antiviral Effects,http://dx.doi.org/10.1371/journal.ppat.1002976,PMC3486884,23133371,CC BY,"Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV) and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H(+)-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.",2012 Oct 25,"['Jurgeit, Andreas', 'McDowell, Robert', 'Moese, Stefan', 'Meldrum, Eric', 'Schwendener, Reto', 'Greber, Urs F.']",PLoS Pathog,,,True
319896275e7fe7dacb19138689294224c13a1aeb,PMC,A Single Residue Substitution in the Receptor-Binding Domain of H5N1 Hemagglutinin Is Critical for Packaging into Pseudotyped Lentiviral Particles,http://dx.doi.org/10.1371/journal.pone.0043596,PMC3487904,23133587,CC BY,"BACKGROUND: Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1. We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for high-throughput serological studies in BSL-2 facilities. Here we show that H5-HAs from different clades do not always give rise to efficient production of H5pp and the underlying mechanisms are addressed. METHODOLOGY/FINDINGS: We have carried out mutational analysis to delineate the molecular determinants responsible for efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005 (H5Anh) into H5pp. Our results demonstrate that a single A134V mutation in the 130-loop of the receptor binding domain is sufficient to render H5Anh the ability to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly hampers production of H5Cam-pp. Although protein expression in total cell lysates is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a significantly higher level than that of H5Anh. We further demonstrate by several independent lines of evidence that the behaviour of H5Anh can be explained by a stronger binding to sialic acid receptors implicating residue 134. CONCLUSIONS: We have identified a single A134V mutation as the molecular determinant in H5-HA for efficient incorporation into H5pp envelope and delineated the underlying mechanism. The reduced binding to sialic acid receptors as a result of the A134V mutation not only exerts a critical influence in pseudotyping efficiency of H5-HA, but has also an impact at the whole virus level. Because A134V substitution has been reported as a naturally occurring mutation in human host, our results may have implications for the understanding of human host adaptation of avian influenza H5N1 viruses.",2012 Nov 2,"['Tang, Dong-Jiang', 'Lam, Yuen-Man', 'Siu, Yu-Lam', 'Lam, Chi-Hong', 'Chu, Shui-Ling', 'Peiris, J. S. Malik', 'Buchy, Philippe', 'Nal, Béatrice', 'Bruzzone, Roberto']",PLoS One,,,True
7c19aadb1294d6b98fc8b947a98eefac0da6b870,PMC,Visual detection of the human metapneumovirus using reverse transcription loop-mediated isothermal amplification with hydroxynaphthol blue dye,http://dx.doi.org/10.1186/1743-422X-9-138,PMC3487928,22838725,CC BY,"BACKGROUND: Human metapneumovirus (hMPV) is a major cause of acute respiratory infections ranging from wheezing to bronchiolitis and pneumonia in children worldwide. The objective of this study is to develop a visual reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of hMPV and applied to the clinical samples. RESULTS: In this study, visual RT-LAMP assay for hMPV was performed in one step with the addition of hydroxynaphthol blue (HNB), and were used to detect respiratory samples. Six primers, including two outer primers (F3 and B3), two inner primers (FIP, BIP) and two loop primers (LF and LB), were designed for hMPV N gene by the online software. Moreover, the RT-LAMP assay showed good specificity and no cross-reactivity was observed with human rhinovirus (HRV), human respiratory syncytial Virus (RSV), or influenza virus A/PR/8/34 (H1N1). The detection limit of the RT-LAMP assay was approximately ten viral RNA copies, lower than that of traditional reverse transcriptase polymerase chain reaction (RT-PCR) 100 RNA copies. In the 176 nasopharyngeal samples, 23 (13.1%) were conformed as hMPV positive by RT-LAMP, but 18 (10.2%) positive by RT-PCR. CONCLUSION: Compared with conventional RT-PCR, the visual hMPV RT-LAMP assay performed well in the aspect of detect time, sensitivity, specificity and visibility. It is anticipated that the RT-LAMP will be used for clinical tests in hospital or field testing during outbreaks and in emergency.",2012 Jul 27,"['Wang, Xiang', 'Zhang, Qian', 'Zhang, Fang', 'Ma, Fenlian', 'Zheng, Wenzhi', 'Zhao, Zhihui', 'Bai, Yinglong', 'Zheng, Lishu']",Virol J,,,True
c0f05769898b94c3e481a16c7fee9666037bbdab,PMC,Isolation and characterization of a variant porcine epidemic diarrhea virus in China,http://dx.doi.org/10.1186/1743-422X-9-195,PMC3487931,22967434,CC BY,"An outbreak of diarrhea in pigs started in Guangdong, South China in January 2011. Cases were characterized by watery diarrhea, dehydration and vomiting, with 80–100% morbidity and 50–90% mortality in suckling piglets. The causative agent of the diarrhea was ultimately identified as porcine epidemic diarrhea virus (PEDV). In this study, we isolated a PEDV strain designated CHGD-01 from piglet intestines using Vero cell cultures, and its specific cytopathic effects were confirmed in susceptible cells by direct immunofluorescence testing and electron microscopy. The complete genome of CHGD-01 was shown to be 28,035 nucleotides in length, with a similar structure to that of PEDV reference strains. Phylogenetic analyses based on the whole genome revealed that CHGD-01 shared nucleotide sequence identities of 98.2–98.4% with two other Chinese isolates reported in the same year, thus constituting a new cluster. Amino acid sequence analysis based on individual virus genes indicated a close relationship between the spike protein gene of CHGD-01 and the field strain KNU0802 in Korea. Its ORF3 and nucleoprotein genes, however, were divergent from all other sequenced PEDV isolate clusters and therefore formed a new group, suggesting a new variant PEDV isolate in China. Further studies will be required to determine the immunogenicity and pathogenicity of this new variant.",2012 Sep 12,"['Pan, Yongfei', 'Tian, Xiaoyan', 'Li, Wei', 'Zhou, Qingfeng', 'Wang, Dongdong', 'Bi, Yingzuo', 'Chen, Feng', 'Song, Yanhua']",Virol J,,,True
e9c8c9036e9dd48230c81ff006be5fceba73660f,PMC,"Megapneumonia Coinfection: pneumococcus, Mycoplasma pneumoniae, and Metapneumovirus",http://dx.doi.org/10.1155/2012/310104,PMC3488377,23193411,CC BY,"We report a young girl who died of Streptococcus pneumoniae 19A pneumonia, septic shock, and hemolytic uremic syndrome despite prior pneumococcal vaccination, appropriate antibiotics, and aggressive intensive care support. Serotype 19A is not covered by the 7- or 10-valent pneumococcal vaccines. Mycoplasma pneumoniae and metapneumovirus were simultaneously detected by PCR in the nasopharyngeal and tracheal aspirates. The pneumococcus is penicillin sensitive. Although infections with each of these pathogens alone are typically mild, this case highlights that co-infection with the triple respiratory pathogens possibly contributed to the fatal outcome of this child. Also, the new policy in Hong Kong to use PCV13 may help prevent further cases of serotype 19A infections.",2012 Oct 17,"['Hon, Kam Lun', 'Ip, Margaret', 'Chu, Winnie Chiu Wing', 'Wong, William']",Case Rep Med,,,True
45a03a7fbd289f6da276b1c0bab12e09337b9ffd,PMC,H1N1 Influenza Viral Infection in a Postpartum Young Woman Causes Respiratory Failure: What the Care Providers Ought to Know?,http://dx.doi.org/10.1155/2012/419528,PMC3488388,23150842,CC BY,"Pregnant and postpartum women are considered a population at increased risk of hospitalization of H1N1 infection. We report the case of a young postpartum woman, who developed evidence of respiratory failure reaching the point of requiring intubation due to an H1N1 influenza virus infection two days after a caesarean delivery. We emphasize the diagnosis, management, and the outcome focusing on the question “what the care providers, including obstetric health care workers, ought to know?” Diagnostic and management strategy for pregnant or postpartum women with novel influenza A (H1N1) viral infection and increased awareness amongst patients and health care professionals may result in improved survival.",2012 Oct 23,"['Aloizos, Stavros', 'Aravosita, Paraskevi', 'Mystakelli, Christina', 'Kanna, Efthymia', 'Gourgiotis, Stavros']",Case Rep Pulmonol,,,True
b2ca7959b768af6c0ac1f5e347a31dacf9fcfd2f,PMC,Sublingual immunization with recombinant adenovirus encoding SARS-CoV spike protein induces systemic and mucosal immunity without redirection of the virus to the brain,http://dx.doi.org/10.1186/1743-422X-9-215,PMC3489719,22995185,CC BY,"BACKGROUND: Sublingual (s.l.) administration of soluble protein antigens, inactivated viruses, or virus-like particles has been shown to induce broad immune responses in mucosal and extra-mucosal tissues. Recombinant replication-defective adenovirus vectors (rADVs) infect mucosa surface and therefore can serve as a mucosal antigen delivery vehicle. In this study we examined whether s.l. immunization with rADV encoding spike protein (S) (rADV-S) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) induces protective immunity against SARS-CoV and could serve as a safe mucosal route for delivery of rADV. RESULTS: Here, we show that s.l. administration of rADV-S induced serum SARS-CoV neutralizing and airway IgA antibodies in mice. These antibody responses are comparable to those induced by intranasal (i.n.) administration. In addition, s.l. immunization induced antigen-specific CD8(+) T cell responses in the lungs that are superior to those induced by intramuscular immunization. Importantly, unlike i.n. administration, s.l. immunization with rADV did not redirect the rADV vector to the olfactory bulb. CONCLUSION: Our study indicates that s.l. immunization with rADV-S is safe and effective in induction of a broad spectrum of immune responses and presumably protection against infection with SARS-CoV.",2012 Sep 21,"['Shim, Byoung-Shik', 'Stadler, Konrad', 'Nguyen, Huan Huu', 'Yun, Cheol-Heui', 'Kim, Dong Wook', 'Chang, Jun', 'Czerkinsky, Cecil', 'Song, Man Ki']",Virol J,,,True
e1a771476018079cd6dcb063ae78e04ca349ba08,PMC,Airway protease/antiprotease imbalance in atopic asthmatics contributes to increased Influenza A virus cleavage and replication,http://dx.doi.org/10.1186/1465-9921-13-82,PMC3489803,22992220,CC BY,"Asthmatics are more susceptible to influenza infections, yet mechanisms mediating this enhanced susceptibility are unknown. Influenza virus hemagglutinin (HA) protein binds to sialic acid residues on the host cells. HA requires cleavage to allow fusion of the viral HA with host cell membrane, which is mediated by host trypsin-like serine protease. We show data here demonstrating that the protease:antiprotease ratio is increased in the nasal mucosa of asthmatics and that these changes were associated with increased proteolytic activation of influenza. These data suggest that disruption of the protease balance in asthmatics enhances activation and infection of influenza virus.",2012 Sep 19,"['Kesic, Matthew J', 'Hernandez, Michelle', 'Jaspers, Ilona']",Respir Res,,,True
2aad3ed695f9313c14066aa2c385092c7cf814b2,PMC,The expression of nicotinic receptor alpha7 during cochlear development,http://dx.doi.org/10.1002/brb3.84,PMC3489815,23139908,CC BY,"Nicotinic acetylcholine receptor alpha7 expression was examined in the developing and adult auditory system using mice that were modified through homologous recombination to coexpress either GFP (alpha7GFP) or Cre (alpha7Cre), respectively. The expression of alpha7GFP is first detected at embryonic (E) day E13.5 in cells of the spiral prominence. By E14.5, sensory regions including the putative outer hair cells and Deiters' cells express alpha7GFP as do solitary efferent fibers. This pattern diminishes after E16.5 in a basal to apex progression, as Hensen's cells and cells of the spiral ligament acquire alpha7GFP expression. At birth and thereafter alpha7GFP also identifies a subset of spiral ganglion cells whose processes terminate on inner hair cells. Efferent fibers identified by peripherin or calcitonin gene-related protein do not coexpress alpha7GFP. In addition to cochlear structures, there is strong expression of alpha7GFP by cells of the central auditory pathways including the ventral posterior cochlear nucleus, lateral lemniscus, central inferior colliculus, and the medial geniculate nucleus. Our findings suggest that alpha7 expression by both neuronal and non-neuronal cells has the potential to impact multiple auditory functions through mechanisms that are not traditionally attributed to this receptor.",2012 Sep 23,"['Rogers, Scott W', 'Myers, Elizabeth J', 'Gahring, Lorise C']",Brain Behav,,,True
cab83150f6a2199249918297638108ce1c45e4e4,PMC,The alcohol industry lobby and Hong Kong’s zero wine and beer tax policy,http://dx.doi.org/10.1186/1471-2458-12-717,PMC3490743,22935365,CC BY,"BACKGROUND: Whereas taxation on alcohol is becoming an increasingly common practice in many countries as part of overall public health measures, the Hong Kong Special Administrative Region Government is bucking the trend and lowered its duties on wine and beer by 50 percent in 2007. In 2008, Hong Kong removed all duties on alcohol except for spirits. The aim of this paper is to examine the case of Hong Kong with its history of changes in alcohol taxation to explore the factors that have driven such an unprecedented policy evolution. METHODS: The research is based on an analysis of primary documents. Searches of official government documents, alcohol-related industry materials and other media reports on alcohol taxation for the period from 2000 to 2008 were systematically carried out using key terms such as “alcohol tax” and “alcohol industry”. Relevant documents (97) were indexed by date and topic to undertake a chronological and thematic analysis using Nvivo8 software. RESULTS: Our analysis demonstrates that whereas the city’s changing financial circumstances and the Hong Kong Special Administrative Region Government’s strong propensity towards economic liberalism had, in part, contributed to such dramatic transformation, the alcohol industry’s lobbying tactics and influence were clearly the main drivers of the policy decision. The alcohol industry’s lobbying tactics were two-fold. The first was to forge a coalition encompassing a range of catering and trade industries related to alcohol as well as industry-friendly lawmakers so that these like-minded actors could find common ground in pursuing changes to the taxation policy. The second was to deliberately promote a blend of ideas to garner support from the general public and to influence the perception of key policy makers. CONCLUSIONS: Our findings suggest that the success of aggressive industry lobbying coupled with the absence of robust public health advocacy was the main driving force behind the unparalleled abolition of wine and beer duties in Hong Kong. Strong public health alliance and advocacy movement are needed to counteract the industry’s continuing aggressive lobby and promotion of alcoholic beverages.",2012 Aug 30,"['Yoon, Sungwon', 'Lam, Tai-Hing']",BMC Public Health,,,True
54ebc03fe88092d143f0758472adf54252d6c224,PMC,Free fatty acids induce ER stress and block antiviral activity of interferon alpha against hepatitis C virus in cell culture,http://dx.doi.org/10.1186/1743-422X-9-143,PMC3490746,22863531,CC BY,"BACKGROUND: Hepatic steatosis is recognized as a major risk factor for liver disease progression and impaired response to interferon based therapy in chronic hepatitis C (CHC) patients. The mechanism of response to interferon-alpha (IFN-α) therapy under the condition of hepatic steatosis is unexplored. We investigated the effect of hepatocellular steatosis on hepatitis C virus (HCV) replication and IFN-α antiviral response in a cell culture model. METHODS: Sub-genomic replicon (S3-GFP) and HCV infected Huh-7.5 cells were cultured with a mixture of saturated (palmitate) and unsaturated (oleate) long-chain free fatty acids (FFA). Intracytoplasmic fat accumulation in these cells was visualized by Nile red staining and electron microscopy then quantified by microfluorometry. The effect of FFA treatment on HCV replication and IFN-α antiviral response was measured by flow cytometric analysis, Renilla luciferase activity, and real-time RT-PCR. RESULTS: FFA treatment induced dose dependent hepatocellular steatosis and lipid droplet accumulation in the HCV replicon cells was confirmed by Nile red staining, microfluorometry, and by electron microscopy. Intracellular fat accumulation supports replication more in the persistently HCV infected culture than in the sub-genomic replicon (S3-GFP) cell line. FFA treatment also partially blocked IFN-α response and viral clearance by reducing the phosphorylation of Stat1 and Stat2 dependent IFN-β promoter activation. We show that FFA treatment induces endoplasmic reticulum (ER) stress response and down regulates the IFNAR1 chain of the type I IFN receptor leading to defective Jak-Stat signaling and impaired antiviral response. CONCLUSION: These results suggest that intracellular fat accumulation in HCV cell culture induces ER stress, defective Jak-Stat signaling, and attenuates the antiviral response, thus providing an explanation to the clinical observation regarding how hepatocellular steatosis influences IFN-α response in CHC.",2012 Aug 3,"['Gunduz, Feyza', 'Aboulnasr, Fatma M', 'Chandra, Partha K', 'Hazari, Sidhartha', 'Poat, Bret', 'Baker, Darren P', 'Balart, Luis A', 'Dash, Srikanta']",Virol J,,,True
da9c223fd6f69816aca093a7d2ab333fe9b21ee1,PMC,Identification of serum proteomic biomarkers for early porcine reproductive and respiratory syndrome (PRRS) infection,http://dx.doi.org/10.1186/1477-5956-10-48,PMC3492009,22873815,CC BY,"BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant swine diseases worldwide. Despite its relevance, serum biomarkers associated with early-onset viral infection, when clinical signs are not detectable and the disease is characterized by a weak anti-viral response and persistent infection, have not yet been identified. Surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) is a reproducible, accurate, and simple method for the identification of biomarker proteins related to disease in serum. This work describes the SELDI-TOF MS analyses of sera of 60 PRRSV-positive and 60 PRRSV-negative, as measured by PCR, asymptomatic Large White piglets at weaning. Sera with comparable and low content of hemoglobin (< 4.52 μg/mL) were fractionated in 6 different fractions by anion-exchange chromatography and protein profiles in the mass range 1–200 kDa were obtained with the CM10, IMAC30, and H50 surfaces. RESULTS: A total of 200 significant peaks (p < 0.05) were identified in the initial discovery phase of the study and 47 of them were confirmed in the validation phase. The majority of peaks (42) were up-regulated in PRRSV-positive piglets, while 5 were down-regulated. A panel of 14 discriminatory peaks identified in fraction 1 (pH = 9), on the surface CM10, and acquired at low focus mass provided a serum protein profile diagnostic pattern that enabled to discriminate between PRRSV-positive and -negative piglets with a sensitivity and specificity of 77% and 73%, respectively. CONCLUSIONS: SELDI-TOF MS profiling of sera from PRRSV-positive and PRRSV-negative asymptomatic piglets provided a proteomic signature with large scale diagnostic potential for early identification of PRRSV infection in weaning piglets. Furthermore, SELDI-TOF protein markers represent a refined phenotype of PRRSV infection that might be useful for whole genome association studies.",2012 Aug 8,"['Genini, Sem', 'Paternoster, Thomas', 'Costa, Alessia', 'Botti, Sara', 'Luini, Mario Vittorio', 'Caprera, Andrea', 'Giuffra, Elisabetta']",Proteome Sci,,,True
f9c39fa24056184c67ec47da4da93ba583c36e84,PMC,In vitro inhibition of transmissible gastroenteritis coronavirus replication in swine testicular cells by short hairpin RNAs targeting the ORF 7 gene,http://dx.doi.org/10.1186/1743-422X-9-176,PMC3492083,22929207,CC BY,"BACKGROUND: Transmissible gastroenteritis (TGE) is a highly contagious viral disease of swine, characterized by severe vomiting, diarrhea, and high mortality. Currently, the vaccines for it are only partially effective and no specific drug is available for treatment of TGE virus (TGEV) infection. RNA interference has been confirmed as a new approach for controlling viral infections. In this study, the inhibitory effect of short hairpin RNAs (shRNAs) targeting the ORF 7 gene of TGEV on virus replication was examined. RESULTS: Four theoretically effective sequences of TGEV ORF 7 gene were designed and selected for construction of shRNA expression plasmids. In the reporter assays, three of four shRNA expression plasmids were able to inhibit significantly the expression of ORF 7 gene and replication of TGEV, as shown by real-time quantitative RT-PCR analysis of viral ORF 7 and N genes and detection of virus titers (TCID(50)/ml). Stable swine testicular (ST) cells expressing the shRNAs were established. Observation of the cytopathic effect and apoptosis, as well as a cell proliferation assay demonstrated that the three shRNAs were capable of protecting ST cells against TGEV destruction, with high specificity and efficiency. CONCLUSIONS: Our results indicated that plasmid-transcribed shRNAs targeting the ORF 7 gene in the TGEV genome effectively inhibited expression of the viral target gene and viral replication in vitro. These findings provide evidence that the shRNAs have potential therapeutic application for treatment of TGE.",2012 Aug 28,"['He, Lei', 'Zhang, Yan-ming', 'Dong, Ling-juan', 'Cheng, Min', 'Wang, Jing', 'Tang, Qing-hai', 'Wang, Gang']",Virol J,,,True
8ce3ae4141f74a6ef60175581277687d6c185b4d,PMC,Social determinants of health in Canada: Are healthy living initiatives there yet? A policy analysis,http://dx.doi.org/10.1186/1475-9276-11-41,PMC3492195,22889402,CC BY,"INTRODUCTION: Preventative strategies that focus on addressing the social determinants of health to improve healthy eating and physical activity have become an important strategy in British Columbia and Ontario for combating chronic diseases. What has not yet been examined is the extent to which healthy living initiatives implemented under these new policy frameworks successfully engage with and change the social determinants of health. METHODS: Initiatives active between January 1, 2006 and September 1, 2011 were found using provincial policy documents, web searches, health organization and government websites, and databases of initiatives that attempted to influence to nutrition and physical activity in order to prevent chronic diseases or improve overall health. Initiatives were reviewed, analyzed and grouped using the descriptive codes: lifestyle-based, environment-based or structure-based. Initiatives were also classified according to the mechanism by which they were administered: as direct programs (e.g. directly delivered), blueprints (or frameworks to tailor developed programs), and building blocks (resources to develop programs). RESULTS: 60 initiatives were identified in Ontario and 61 were identified in British Columbia. In British Columbia, 11.5% of initiatives were structure-based. In Ontario, of 60 provincial initiatives identified, 15% were structure-based. Ontario had a higher proportion of direct interventions than British Columbia for all intervention types. However, in both provinces, as the intervention became more upstream and attempted to target the social determinants of health more directly, the level of direct support for the intervention lessened. CONCLUSIONS: The paucity of initiatives in British Columbia and Ontario that address healthy eating and active living through action on the social determinants of health is problematic. In the context of Canada's increasingly neoliberal political and economic policy, the public health sector may face significant barriers to addressing upstream determinants in a meaningful way. If public health cannot directly affect broader societal conditions, interventions should be focused around advocacy and education about the social determinants of health. It is necessary that health be seen for what it is: a political matter. As such, the health sector needs to take a more political approach in finding solutions for health inequities.",2012 Aug 14,"['Gore, Dana', 'Kothari, Anita']",Int J Equity Health,,,True
01c6ab71344d688b1b44fd2095d891d126152499,PMC,Social determinants of health in Canada: Are healthy living initiatives there yet? A policy analysis,http://dx.doi.org/10.1186/1475-9276-11-41,PMC3492195,22889402,CC BY,"INTRODUCTION: Preventative strategies that focus on addressing the social determinants of health to improve healthy eating and physical activity have become an important strategy in British Columbia and Ontario for combating chronic diseases. What has not yet been examined is the extent to which healthy living initiatives implemented under these new policy frameworks successfully engage with and change the social determinants of health. METHODS: Initiatives active between January 1, 2006 and September 1, 2011 were found using provincial policy documents, web searches, health organization and government websites, and databases of initiatives that attempted to influence to nutrition and physical activity in order to prevent chronic diseases or improve overall health. Initiatives were reviewed, analyzed and grouped using the descriptive codes: lifestyle-based, environment-based or structure-based. Initiatives were also classified according to the mechanism by which they were administered: as direct programs (e.g. directly delivered), blueprints (or frameworks to tailor developed programs), and building blocks (resources to develop programs). RESULTS: 60 initiatives were identified in Ontario and 61 were identified in British Columbia. In British Columbia, 11.5% of initiatives were structure-based. In Ontario, of 60 provincial initiatives identified, 15% were structure-based. Ontario had a higher proportion of direct interventions than British Columbia for all intervention types. However, in both provinces, as the intervention became more upstream and attempted to target the social determinants of health more directly, the level of direct support for the intervention lessened. CONCLUSIONS: The paucity of initiatives in British Columbia and Ontario that address healthy eating and active living through action on the social determinants of health is problematic. In the context of Canada's increasingly neoliberal political and economic policy, the public health sector may face significant barriers to addressing upstream determinants in a meaningful way. If public health cannot directly affect broader societal conditions, interventions should be focused around advocacy and education about the social determinants of health. It is necessary that health be seen for what it is: a political matter. As such, the health sector needs to take a more political approach in finding solutions for health inequities.",2012 Aug 14,"['Gore, Dana', 'Kothari, Anita']",Int J Equity Health,,,False
9663932b573dbf156ca3ca89873b43a62ea3a6fa,PMC,Social determinants of health in Canada: Are healthy living initiatives there yet? A policy analysis,http://dx.doi.org/10.1186/1475-9276-11-41,PMC3492195,22889402,CC BY,"INTRODUCTION: Preventative strategies that focus on addressing the social determinants of health to improve healthy eating and physical activity have become an important strategy in British Columbia and Ontario for combating chronic diseases. What has not yet been examined is the extent to which healthy living initiatives implemented under these new policy frameworks successfully engage with and change the social determinants of health. METHODS: Initiatives active between January 1, 2006 and September 1, 2011 were found using provincial policy documents, web searches, health organization and government websites, and databases of initiatives that attempted to influence to nutrition and physical activity in order to prevent chronic diseases or improve overall health. Initiatives were reviewed, analyzed and grouped using the descriptive codes: lifestyle-based, environment-based or structure-based. Initiatives were also classified according to the mechanism by which they were administered: as direct programs (e.g. directly delivered), blueprints (or frameworks to tailor developed programs), and building blocks (resources to develop programs). RESULTS: 60 initiatives were identified in Ontario and 61 were identified in British Columbia. In British Columbia, 11.5% of initiatives were structure-based. In Ontario, of 60 provincial initiatives identified, 15% were structure-based. Ontario had a higher proportion of direct interventions than British Columbia for all intervention types. However, in both provinces, as the intervention became more upstream and attempted to target the social determinants of health more directly, the level of direct support for the intervention lessened. CONCLUSIONS: The paucity of initiatives in British Columbia and Ontario that address healthy eating and active living through action on the social determinants of health is problematic. In the context of Canada's increasingly neoliberal political and economic policy, the public health sector may face significant barriers to addressing upstream determinants in a meaningful way. If public health cannot directly affect broader societal conditions, interventions should be focused around advocacy and education about the social determinants of health. It is necessary that health be seen for what it is: a political matter. As such, the health sector needs to take a more political approach in finding solutions for health inequities.",2012 Aug 14,"['Gore, Dana', 'Kothari, Anita']",Int J Equity Health,,,False
b1b9699bbe9b36657ae6aa66628dc06e232da95b,PMC,"Serological evidence of ebolavirus infection in bats, China",http://dx.doi.org/10.1186/1743-422X-9-236,PMC3492202,23062147,CC BY,"BACKGROUND: The genus Ebolavirus of the family Filoviridae currently consists of five species. All species, with the exception of Reston ebolavirus, have been found in Africa and caused severe human diseases. Bats have been implicated as reservoirs for ebolavirus. Reston ebolavirus, discovered in the Philippines, is the only ebolavirus species identified in Asia to date. Whether this virus is prevalent in China is unknown. FINDINGS: In this study, we developed an enzyme linked immunosorbent assay (ELISA) for ebolavirus using the recombinant nucleocapsid protein and performed sero-surveillance for the virus among Chinese bat populations. Our results revealed the presence of antibodies to ebolavirus in 32 of 843 bat sera samples and 10 of 16 were further confirmed by western blot analysis. CONCLUSION: To our knowledge, this is the first report of any filovirus infection in China.",2012 Oct 13,"['Yuan, Junfa', 'Zhang, Yuji', 'Li, Jialu', 'Zhang, Yunzhi', 'Wang, Lin-Fa', 'Shi, Zhengli']",Virol J,,,True
883b77a8f0dfe0d099e0ceb77531f18fc8a6b2a9,PMC,Immunogenetic Variation and Differential Pathogen Exposure in Free-Ranging Cheetahs across Namibian Farmlands,http://dx.doi.org/10.1371/journal.pone.0049129,PMC3492310,23145096,CC BY,"BACKGROUND: Genes under selection provide ecologically important information useful for conservation issues. Major histocompatibility complex (MHC) class I and II genes are essential for the immune defence against pathogens from intracellular (e.g. viruses) and extracellular (e.g. helminths) origins, respectively. Serosurvey studies in Namibian cheetahs (Acinonyx juabuts) revealed higher exposure to viral pathogens in individuals from north-central than east-central regions. Here we examined whether the observed differences in exposure to viruses influence the patterns of genetic variation and differentiation at MHC loci in 88 free-ranging Namibian cheetahs. METHODOLOGY/PRINCIPAL FINDINGS: Genetic variation at MHC I and II loci was assessed through single-stranded conformation polymorphism (SSCP) analysis and sequencing. While the overall allelic diversity did not differ, we observed a high genetic differentiation at MHC class I loci between cheetahs from north-central and east-central Namibia. No such differentiation in MHC class II and neutral markers were found. CONCLUSIONS/SIGNIFICANCE: Our results suggest that MHC class I variation mirrors the variation in selection pressure imposed by viruses in free-ranging cheetahs across Namibian farmland. This is of high significance for future management and conservation programs of this species.",2012 Nov 7,"['Castro-Prieto, Aines', 'Wachter, Bettina', 'Melzheimer, Joerg', 'Thalwitzer, Susanne', 'Hofer, Heribert', 'Sommer, Simone']",PLoS One,,,True
5678f2e8dc1710c96b5f4e5ae8d6ddae9c5e6580,PMC,Production and characterization of human anti-V3 monoclonal antibodies from the cells of HIV-1 infected Indian donors,http://dx.doi.org/10.1186/1743-422X-9-196,PMC3493341,22971578,CC BY,"BACKGROUND: Analysis of human monoclonal antibodies (mAbs) developed from HIV-1 infected donors have enormously contributed to the identification of neutralization sensitive epitopes on the HIV-1 envelope glycoprotein. The third variable region (V3) is a crucial target on gp120, primarily due to its involvement in co-receptor (CXCR4 or CCR5) binding and presence of epitopes recognized by broadly neutralizing antibodies. METHODS: Thirty-three HIV-1 seropositive drug naive patients (18 males and 15 females) within the age range of 20–57 years (median = 33 years) were recruited in this study for mAb production. The mAbs were selected from EBV transformed cultures with conformationally constrained Cholera-toxin-B containing V3C (V3C-CTB) fusion protein. We tested the mAbs for their binding with HIV-1 derived proteins and peptides by ELISA and for neutralization against HIV-1 viruses by TZM-bl assays. RESULTS: We isolated three anti-V3 mAbs, 277, 903 and 904 from the cells of different individuals. The ELISA binding revealed a subtype-C and subtype-A specific binding of antibody 277 and 903 while mAb 904 exhibited cross reactivity also with subtype-B V3. Epitope mapping of mAbs with overlapping V3 peptides showed exclusive binding to V3 crown. The antibodies displayed high and low neutralizing activity against 2/5 tier 1 and 1/6 tier 2 viruses respectively. Overall, we observed a resistance of the tier 2 viruses to neutralization by the anti-V3 mAbs, despite the exposure of the epitopes recognized by these antibodies on two representative native viruses (Du156.12 and JRFL), suggesting that the affinity of mAb might equally be crucial for neutralization, as the epitope recognition. CONCLUSIONS: Our study suggests that the anti-V3 antibodies derived from subtype-C infected Indian patients display neutralization potential against tier 1 viruses while such activity may be limited against more resistant tier 2 viruses. Defining the fine epitope specificities of these mAbs and further experimental manipulations will be helpful in identification of epitopes, unique to clade C or shared with non-clade C viruses, in context of V3 region.",2012 Sep 12,"['Andrabi, Raiees', 'Kumar, Rajesh', 'Bala, Manju', 'Nair, Ambili', 'Biswas, Ashutosh', 'Wig, Naveet', 'Kumar, Pratik', 'Pal, Rahul', 'Sinha, Subrata', 'Luthra, Kalpana']",Virol J,,,True
624d182cc7495a9fd996eb51663e8774a42d2cca,PMC,Evidence-based support for the all-hazards approach to emergency preparedness,http://dx.doi.org/10.1186/2045-4015-1-40,PMC3494498,23098065,CC BY,"BACKGROUND: During the last decade there has been a need to respond and recover from various types of emergencies including mass casualty events (MCEs), mass toxicological/chemical events (MTEs), and biological events (pandemics and bio-terror agents). Effective emergency preparedness is more likely to be achieved if an all-hazards response plan is adopted. OBJECTIVES: To investigate if there is a relationship among hospitals' preparedness for various emergency scenarios, and whether components of one emergency scenario correlate with preparedness for other emergency scenarios. METHODS: Emergency preparedness levels of all acute-care hospitals for MCEs, MTEs, and biological events were evaluated, utilizing a structured evaluation tool based on measurable parameters. Evaluations were made by professional experts in two phases: evaluation of standard operating procedures (SOPs) followed by a site visit. Relationships among total preparedness and different components' scores for various types of emergencies were analyzed. RESULTS: Significant relationships were found among preparedness for different emergencies. Standard Operating Procedures (SOPs) for biological events correlated with preparedness for all investigated emergency scenarios. Strong correlations were found between training and drills with preparedness for all investigated emergency scenarios. CONCLUSIONS: Fundamental critical building blocks such as SOPs, training, and drill programs improve preparedness for different emergencies including MCEs, MTEs, and biological events, more than other building blocks, such as equipment or knowledge of personnel. SOPs are especially important in unfamiliar emergency scenarios. The findings support the adoption of an all-hazards approach to emergency preparedness.",2012 Oct 25,"['Adini, Bruria', 'Goldberg, Avishay', 'Cohen, Robert', 'Laor, Daniel', 'Bar-Dayan, Yaron']",Isr J Health Policy Res,,,True
2b10c237281a6e5d61e8fff995dc8920465eda56,PMC,"Simultaneous Detection and Differentiation of Human Papillomavirus Genotypes 6, 11, 16 and 18 by AllGlo Quadruplex Quantitative PCR",http://dx.doi.org/10.1371/journal.pone.0048972,PMC3494670,23152833,CC BY,"BACKGROUND: Human papillomaviruses (HPV) are classified into high-risk HPV and low-risk HPV. The most common high-risk HPV types in cervical cancer are HPV 16 and 18, and the most common low-risk types causing genital warts are HPV 6 and HPV 11. In this study, applying novel AllGlo fluorescent probes, we established a quadruplex quantitative PCR method to simultaneously detect and differentiate HPV 6, 11, 16 and 18 in a single tube. METHODS: The specificity, the sensitivity, the detection limit, the reproducibility and the standard curve of this method were examined. Finally, clinical samples that had been tested previously by TaqMan PCR and HPV GenoArray (GA) test were used to verify the accuracy and sensitivity of the method. RESULTS: The assay has a sensitivity of 10(1) to 10(2) copies/test and a linear detection range from 10(1) to 10(8) copies/test. The mean amplification efficiencies for HPV 6, 11, 16, and 18 were 0.97, 1.10, 0.93 and 1.20, respectively, and the mean correlation coefficient (r(2)) of each standard curve was above 0.99 for plasmid templates ranging from 10(3) to 10(7) copies/test. There was 100% agreement between the AllGlo quadruplex quantitative PCR, HPV GA test and TaqMan uniplex qPCR methods. CONCLUSIONS: AllGlo quadruplex quantitative PCR in a single tube has the advantages of relatively high throughput, good reproducibility, high sensitivity, high specificity, and a wide linear range of detection. The convenient single tube format makes this assay a powerful tool for the studies of mixed infections by multiple pathogens, viral typing and viral load quantification.",2012 Nov 9,"['Yu, Daojun', 'Chen, Yu', 'Wu, Shenghai', 'Wang, Baohong', 'Tang, Yi-Wei', 'Li, Lanjuan']",PLoS One,,,True
bf7d69e6d9d85c3870025ee9e51632ca44283441,PMC,Epitope mapping by random peptide phage display reveals essential residues for vaccinia extracellular enveloped virion spread,http://dx.doi.org/10.1186/1743-422X-9-217,PMC3495767,23006741,CC BY,"BACKGROUND: A33 is a type II integral membrane protein expressed on the extracellular enveloped form of vaccinia virus (VACV). Passive transfer of A33-directed monoclonal antibodies or vaccination with an A33 subunit vaccine confers protection against lethal poxvirus challenge in animal models. Homologs of A33 are highly conserved among members of the Orthopoxvirus genus and are potential candidates for inclusion in vaccines or assays targeting extracellular enveloped virus activity. One monoclonal antibody directed against VACV A33, MAb-1G10, has been shown to target a conformation-dependent epitope. Interestingly, while it recognizes VACV A33 as well as the corresponding variola homolog, it does not bind to the monkeypox homolog. In this study, we utilized a random phage display library to investigate the epitope recognized by MAb-1G10 that is critical for facilitating cell-to-cell spread of the vaccinia virus. RESULTS: By screening with linear or conformational random phage libraries, we found that phages binding to MAb-1G10 display the consensus motif CEPLC, with a disulfide bond formed between two cysteine residues required for MAb-1G10 binding. Although the phage motif contained no linear sequences homologous to VACV A33, structure modeling and analysis suggested that residue D115 is important to form the minimal epitope core. A panel of point mutants expressing the ectodomain of A33 protein was generated and analyzed by either binding assays such as ELISA and immunoprecipitation or a functional assessment by blocking MAb-1G10 mediated comet inhibition in cell culture. CONCLUSIONS: These results confirm L118 as a component of the MAb-1G10 binding epitope, and further identify D115 as an essential residue. By defining the minimum conformational structure, as well as the conformational arrangement of a short peptide sequence recognized by MAb-1G10, these results introduce the possibility of designing small molecule mimetics that may interfere with the function of A33 in vivo. This information will also be useful for designing improved assays to evaluate the potency of monoclonal and polyclonal products that target A33 or A33-modulated EV dissemination.",2012 Sep 24,"['He, Yong', 'Wang, Yonggang', 'Struble, Evi B', 'Zhang, Pei', 'Chowdhury, Soma', 'Reed, Jennifer L', 'Kennedy, Michael', 'Scott, Dorothy E', 'Fisher, Robert W']",Virol J,,,True
f2b40d30efe21fe521d22798d4c0e185e4ad6799,PMC,PCR based bronchoscopic detection of common respiratory pathogens in chronic cough: a case control study,http://dx.doi.org/10.1186/1745-9974-8-5,PMC3496690,22978556,CC BY,"BACKGROUND: Viral respiratory tract infection is the most frequent cause of acute cough and is reported at onset in about one third of patients with chronic cough. Persistent infection is therefore one possible explanation for the cough reflex hypersensitivity and pulmonary inflammation reported in chronic cough patients. METHODS: Bronchoscopic endobronchial biopsies and bronchoalveolar lavage cell counts were obtained from ten healthy volunteers and twenty treatment resistant chronic cough patients (10 selected for lavage lymphocytosis). A screen for known respiratory pathogens was performed on biopsy tissue. Chronic cough patients also underwent cough reflex sensitivity testing using citric acid. RESULTS: There was no significant difference in incidence of infection between healthy volunteers and chronic cough patients (p = 0.115) or non-lymphocytic and lymphocytic groups (p = 0.404). BAL cell percentages were not significantly different between healthy volunteers and chronic cough patients without lymphocytosis. Lymphocytic patients however had a significantly raised percentage of lymphocytes (p < 0.01), neutrophils (p < 0.05), eosinophils (p < 0.05) and decreased macrophages (p < 0.001) verses healthy volunteers. There was no significant difference in the cough reflex sensitivity between non-lymphocytic and lymphocytic patients (p = 0.536). CONCLUSIONS: This study indicates latent infection in the lung is unlikely to play an important role in chronic cough, but a role for undetected or undetectable pathogens in either the lung or a distal site could not be ruled out. TRIALS REGISTRATION: Current Controlled Trials ISRCTN62337037 & ISRCTN40147207",2012 Sep 14,"['West, Peter W', 'Kelsall, Angela', 'Decalmer, Samantha', 'Dove, Winifred', 'Bishop, Paul W', 'Stewart, James P', 'Woodcock, Ashley A', 'Smith, Jaclyn A']",Cough,,,True
8c5bd7a3606dc60cc568fb2614c8a5bdc00bffbb,PMC,PCR based bronchoscopic detection of common respiratory pathogens in chronic cough: a case control study,http://dx.doi.org/10.1186/1745-9974-8-5,PMC3496690,22978556,CC BY,"BACKGROUND: Viral respiratory tract infection is the most frequent cause of acute cough and is reported at onset in about one third of patients with chronic cough. Persistent infection is therefore one possible explanation for the cough reflex hypersensitivity and pulmonary inflammation reported in chronic cough patients. METHODS: Bronchoscopic endobronchial biopsies and bronchoalveolar lavage cell counts were obtained from ten healthy volunteers and twenty treatment resistant chronic cough patients (10 selected for lavage lymphocytosis). A screen for known respiratory pathogens was performed on biopsy tissue. Chronic cough patients also underwent cough reflex sensitivity testing using citric acid. RESULTS: There was no significant difference in incidence of infection between healthy volunteers and chronic cough patients (p = 0.115) or non-lymphocytic and lymphocytic groups (p = 0.404). BAL cell percentages were not significantly different between healthy volunteers and chronic cough patients without lymphocytosis. Lymphocytic patients however had a significantly raised percentage of lymphocytes (p < 0.01), neutrophils (p < 0.05), eosinophils (p < 0.05) and decreased macrophages (p < 0.001) verses healthy volunteers. There was no significant difference in the cough reflex sensitivity between non-lymphocytic and lymphocytic patients (p = 0.536). CONCLUSIONS: This study indicates latent infection in the lung is unlikely to play an important role in chronic cough, but a role for undetected or undetectable pathogens in either the lung or a distal site could not be ruled out. TRIALS REGISTRATION: Current Controlled Trials ISRCTN62337037 & ISRCTN40147207",2012 Sep 14,"['West, Peter W', 'Kelsall, Angela', 'Decalmer, Samantha', 'Dove, Winifred', 'Bishop, Paul W', 'Stewart, James P', 'Woodcock, Ashley A', 'Smith, Jaclyn A']",Cough,,,True
2ad78e3c71255e44a415f1e3c933ba418f19c4ee,PMC,PCR based bronchoscopic detection of common respiratory pathogens in chronic cough: a case control study,http://dx.doi.org/10.1186/1745-9974-8-5,PMC3496690,22978556,CC BY,"BACKGROUND: Viral respiratory tract infection is the most frequent cause of acute cough and is reported at onset in about one third of patients with chronic cough. Persistent infection is therefore one possible explanation for the cough reflex hypersensitivity and pulmonary inflammation reported in chronic cough patients. METHODS: Bronchoscopic endobronchial biopsies and bronchoalveolar lavage cell counts were obtained from ten healthy volunteers and twenty treatment resistant chronic cough patients (10 selected for lavage lymphocytosis). A screen for known respiratory pathogens was performed on biopsy tissue. Chronic cough patients also underwent cough reflex sensitivity testing using citric acid. RESULTS: There was no significant difference in incidence of infection between healthy volunteers and chronic cough patients (p = 0.115) or non-lymphocytic and lymphocytic groups (p = 0.404). BAL cell percentages were not significantly different between healthy volunteers and chronic cough patients without lymphocytosis. Lymphocytic patients however had a significantly raised percentage of lymphocytes (p < 0.01), neutrophils (p < 0.05), eosinophils (p < 0.05) and decreased macrophages (p < 0.001) verses healthy volunteers. There was no significant difference in the cough reflex sensitivity between non-lymphocytic and lymphocytic patients (p = 0.536). CONCLUSIONS: This study indicates latent infection in the lung is unlikely to play an important role in chronic cough, but a role for undetected or undetectable pathogens in either the lung or a distal site could not be ruled out. TRIALS REGISTRATION: Current Controlled Trials ISRCTN62337037 & ISRCTN40147207",2012 Sep 14,"['West, Peter W', 'Kelsall, Angela', 'Decalmer, Samantha', 'Dove, Winifred', 'Bishop, Paul W', 'Stewart, James P', 'Woodcock, Ashley A', 'Smith, Jaclyn A']",Cough,,,False
062d0779c4b304f4188666a3989152d9f9557340,PMC,High Content Image Based Analysis Identifies Cell Cycle Inhibitors as Regulators of Ebola Virus Infection,http://dx.doi.org/10.3390/v4101865,PMC3497033,23202445,CC BY,"Viruses modulate a number of host biological responses including the cell cycle to favor their replication. In this study, we developed a high-content imaging (HCI) assay to measure DNA content and identify different phases of the cell cycle. We then investigated the potential effects of cell cycle arrest on Ebola virus (EBOV) infection. Cells arrested in G1 phase by serum starvation or G1/S phase using aphidicolin or G2/M phase using nocodazole showed much reduced EBOV infection compared to the untreated control. Release of cells from serum starvation or aphidicolin block resulted in a time-dependent increase in the percentage of EBOV infected cells. The effect of EBOV infection on cell cycle progression was found to be cell-type dependent. Infection of asynchronous MCF-10A cells with EBOV resulted in a reduced number of cells in G2/M phase with concomitant increase of cells in G1 phase. However, these effects were not observed in HeLa or A549 cells. Together, our studies suggest that EBOV requires actively proliferating cells for efficient replication. Furthermore, multiplexing of HCI based assays to detect viral infection, cell cycle status and other phenotypic changes in a single cell population will provide useful information during screening campaigns using siRNA and small molecule therapeutics.",2012 Sep 25,"['Kota, Krishna P.', 'Benko, Jacqueline G.', 'Mudhasani, Rajini', 'Retterer, Cary', 'Tran, Julie P.', 'Bavari, Sina', 'Panchal, Rekha G.']",Viruses,,,True
7d0c3cb7b6d6dfcb416028248132542c99f80ba0,PMC,Forty-Five Years of Marburg Virus Research,http://dx.doi.org/10.3390/v4101878,PMC3497034,23202446,CC BY,"In 1967, the first reported filovirus hemorrhagic fever outbreak took place in Germany and the former Yugoslavia. The causative agent that was identified during this outbreak, Marburg virus, is one of the most deadly human pathogens. This article provides a comprehensive overview of our current knowledge about Marburg virus disease ranging from ecology to pathogenesis and molecular biology.",2012 Oct 1,"['Brauburger, Kristina', 'Hume, Adam J.', 'Mühlberger, Elke', 'Olejnik, Judith']",Viruses,,,True
06e89cafce095f075c8a197fbdfb78c259133a8b,PMC,Pathogenesis of Lassa Fever,http://dx.doi.org/10.3390/v4102031,PMC3497040,23202452,CC BY,"Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host’s immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents.",2012 Oct 9,"['Yun, Nadezhda E.', 'Walker, David H.']",Viruses,,,True
f1d308db379b3c293bcfc8fe251c043fe8842358,PMC,Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers,http://dx.doi.org/10.3390/v4102097,PMC3497043,23202455,CC BY,"The family Arenaviridae, genus Arenavirus, consists of two phylogenetically independent groups: Old World (OW) and New World (NW) complexes. The Lassa and Lujo viruses in the OW complex and the Guanarito, Junin, Machupo, Sabia, and Chapare viruses in the NW complex cause viral hemorrhagic fever (VHF) in humans, leading to serious public health concerns. These viruses are also considered potential bioterrorism agents. Therefore, it is of great importance to detect these pathogens rapidly and specifically in order to minimize the risk and scale of arenavirus outbreaks. However, these arenaviruses are classified as BSL-4 pathogens, thus making it difficult to develop diagnostic techniques for these virus infections in institutes without BSL-4 facilities. To overcome these difficulties, antibody detection systems in the form of an enzyme-linked immunosorbent assay (ELISA) and an indirect immunofluorescence assay were developed using recombinant nucleoproteins (rNPs) derived from these viruses. Furthermore, several antigen-detection assays were developed. For example, novel monoclonal antibodies (mAbs) to the rNPs of Lassa and Junin viruses were generated. Sandwich antigen-capture (Ag-capture) ELISAs using these mAbs as capture antibodies were developed and confirmed to be sensitive and specific for detecting the respective arenavirus NPs. These rNP-based assays were proposed to be useful not only for an etiological diagnosis of VHFs, but also for seroepidemiological studies on VHFs. We recently developed arenavirus neutralization assays using vesicular stomatitis virus (VSV)-based pseudotypes bearing arenavirus recombinant glycoproteins. The goal of this article is to review the recent advances in developing laboratory diagnostic assays based on recombinant viral proteins for the diagnosis of VHFs and epidemiological studies on the VHFs caused by arenaviruses.",2012 Oct 12,"['Fukushi, Shuetsu', 'Tani, Hideki', 'Yoshikawa, Tomoki', 'Saijo, Masayuki', 'Morikawa, Shigeru']",Viruses,,,True
12c7bde10bc2422a099a326c99cba1ec1e496431,PMC,D471G Mutation in LCMV-NP Affects its Ability to Self-associate and Results in a Dominant Negative Effect in Viral RNA Synthesis,http://dx.doi.org/10.3390/v4102137,PMC3497045,23202457,CC BY,"Arenaviruses merit significant interest because several family members are etiological agents of severe hemorrhagic fevers, representing a major burden to public health. Currently, there are no FDA-licensed vaccines against arenaviruses and the only available antiviral therapy is limited to the use of ribavirin that is partially effective. Arenavirus nucleoprotein (NP) is found associated with the genomic RNA forming the viral ribonucleoproteins (vRNPs) that together with the polymerase (L) direct viral replication and transcription. Virion formation requires the recruitment of vRNPs into budding sites, a process in which the arenavirus matrix-like protein (Z) plays a major role. Therefore, proper NP-NP and NP-Z interactions are required for the generation of infectious progeny. In this work we demonstrate the role of the amino acid residue D471 in the self-association of lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP). Amino acid substitutions at this position abrogate NP oligomerization, affecting its ability to mediate replication and transcription of a minigenome reporter plasmid. However, its ability to interact with the Z protein, counteract the cellular interferon response and bind to dsRNA analogs was retained. Additionally, we also document the dominant negative effect of D471G mutation on viral infection, suggesting that NP self-association is an excellent target for the development of new antivirals against arenaviruses.",2012 Oct 16,"['Ortiz-Riaño, Emilio', 'Cheng, Benson Y. H.', 'de la Torre, Juan C.', 'Martínez-Sobrido, Luis']",Viruses,,,True
33bee45e93ec92d0813e39a07e158605af679215,PMC,Hepatitis C Virus and Cellular Stress Response: Implications to Molecular Pathogenesis of Liver Diseases,http://dx.doi.org/10.3390/v4102251,PMC3497051,23202463,CC BY,"Infection with hepatitis C virus (HCV) is a leading risk factor for chronic liver disease progression, including steatosis, cirrhosis, and hepatocellular carcinoma. With approximately 3% of the human population infected worldwide, HCV infection remains a global public health challenge. The efficacy of current therapy is still limited in many patients infected with HCV, thus a greater understanding of pathogenesis in HCV infection is desperately needed. Emerging lines of evidence indicate that HCV triggers a wide range of cellular stress responses, including cell cycle arrest, apoptosis, endoplasmic reticulum (ER) stress/unfolded protein response (UPR), and autophagy. Also, recent studies suggest that these HCV-induced cellular responses may contribute to chronic liver diseases by modulating cell proliferation, altering lipid metabolism, and potentiating oncogenic pathways. However, the molecular mechanism underlying HCV infection in the pathogenesis of chronic liver diseases still remains to be determined. Here, we review the known stress response activation in HCV infection in vitro and in vivo, and also explore the possible relationship of a variety of cellular responses with the pathogenicity of HCV-associated diseases. Comprehensive knowledge of HCV-mediated disease progression shall shed new insights into the discovery of novel therapeutic targets and the development of new intervention strategy.",2012 Oct 19,"['Ke, Po-Yuan', 'Chen, Steve S.-L.']",Viruses,,,True
e42f45097fff6577e1ba2da76661b56f7bff299a,PMC,Fragment-Based Screening by Protein Crystallography: Successes and Pitfalls,http://dx.doi.org/10.3390/ijms131012857,PMC3497300,23202926,CC BY,"Fragment-based drug discovery (FBDD) concerns the screening of low-molecular weight compounds against macromolecular targets of clinical relevance. These compounds act as starting points for the development of drugs. FBDD has evolved and grown in popularity over the past 15 years. In this paper, the rationale and technology behind the use of X-ray crystallography in fragment based screening (FBS) will be described, including fragment library design and use of synchrotron radiation and robotics for high-throughput X-ray data collection. Some recent uses of crystallography in FBS will be described in detail, including interrogation of the drug targets β-secretase, phenylethanolamine N-methyltransferase, phosphodiesterase 4A and Hsp90. These examples provide illustrations of projects where crystallography is straightforward or difficult, and where other screening methods can help overcome the limitations of crystallography necessitated by diffraction quality.",2012 Oct 8,"['Chilingaryan, Zorik', 'Yin, Zhou', 'Oakley, Aaron J.']",Int J Mol Sci,,,True
9bbac1f67fbab1d4f3e9a20387a63989bf40bfad,PMC,Multiple Sclerosis: The Role of Cytokines in Pathogenesis and in Therapies,http://dx.doi.org/10.3390/ijms131013438,PMC3497335,23202961,CC BY,"Multiple sclerosis, the clinical features and pathological correlate for which were first described by Charcot, is a chronic neuroinflammatory disease with unknown etiology and variable clinical evolution. Although neuroinflammation is a descriptive denominator in multiple sclerosis based on histopathological observations, namely the penetration of leukocytes into the central nervous system, the clinical symptoms of relapses, remissions and progressive paralysis are the result of losses of myelin and neurons. In the absence of etiological factors as targets for prevention and therapy, the definition of molecular mechanisms that form the basis of inflammation, demyelination and toxicity for neurons have led to a number of treatments that slow down disease progression in specific patient cohorts, but that do not cure the disease. Current therapies are directed to block the immune processes, both innate and adaptive, that are associated with multiple sclerosis. In this review, we analyze the role of cytokines in the multiple sclerosis pathogenesis and current/future use of them in treatments of multiple sclerosis.",2012 Oct 19,"['Amedei, Amedeo', 'Prisco, Domenico', 'D’Elios, Mario Milco']",Int J Mol Sci,,,True
cb55f63de6946c57d21275e45c94c79955bba977,PMC,The Criteria to Confirm the Role of Epstein-Barr Virus in Nasopharyngeal Carcinoma Initiation,http://dx.doi.org/10.3390/ijms131013737,PMC3497352,23202978,CC BY,"Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC), but it remains obscure whether EBV is a viral cause of, or only an accompaniment of, NPC. We will discuss the accumulated evidence pointing to the relationship between EBV infection and NPC initiation from epidemiologic, pathogenic, molecular oncogenic, and experimental animal studies. We believe that convincing evidence from these perspectives must be provided before we can ascertain the causal role of EBV infection in NPC. Specifically, (1) epidemiological studies should reveal EBV infection as a risk factor; (2) the introduction of EBV into an animal model should produce NPC; (3) in the animal model NPC, the main molecular event(s) or the involved signaling pathway(s) should be identical to that in human NPC; and (4) finally and most importantly, prevention of EBV infection or clearance of EBV from infected individuals must be able to reduce the incidence rate of NPC.",2012 Oct 23,"['Gu, Ai-Di', 'Zeng, Mu-Sheng', 'Qian, Chao-Nan']",Int J Mol Sci,,,True
cc5ffabf819570a8912666ecdb9de62cb48e0387,PMC,Equivalence of Self- and Staff-Collected Nasal Swabs for the Detection of Viral Respiratory Pathogens,http://dx.doi.org/10.1371/journal.pone.0048508,PMC3498275,23155387,CC BY,"BACKGROUND: The need for the timely collection of diagnostic biosamples during symptomatic episodes represents a major obstacle to large-scale studies on acute respiratory infection (ARI) epidemiology. This may be circumvented by having the participants collect their own nasal swabs. We compared self- and staff-collected swabs in terms of swabbing quality and detection of viral respiratory pathogens. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a prospective study among employees of our institution during the ARI season 2010/2011 (December-March). Weekly emails were sent to the participants (n = 84), reminding them to come to the study center in case of new symptoms. The participants self-collected an anterior nasal swab from one nostril, and trained study personnel collected one from the other nostril. The participants self-collected another two swabs (one from each nostril) on a subsequent day. Human β-actin DNA concentration was determined in the swabs as a quality control. Viral respiratory pathogens were detected by multiplex RT-PCR (Seeplex RV15 kit, Seegene, Eschborn, Germany). Of 84 participants, 56 (67%) reported at least one ARI episode, 18 participants two, and one participant three. Self-swabbing was highly accepted by the participants. The amount of β-actin DNA per swab was higher in the self- than in the staff-collected swabs (p = 0.008). β-actin concentration was lower in the self-swabs collected on day 1 than in those collected on a subsequent day (p<0.0001). A respiratory viral pathogen was detected in 31% (23/75) of staff- and in 35% (26/75) of self-collected swabs (p = 0.36). With both approaches, the most frequently identified pathogens were human rhinoviruses A/B/C (12/75 swabs, 16%) and human coronavirus OC43 (4/75 swabs, 5%). There was almost perfect agreement between self- and staff-collected swabs in terms of pathogen detection (agreement = 93%, kappa = 0.85, p<0.0001). CONCLUSIONS/SIGNIFICANCE: Nasal self-swabbing for identification of viral ARI pathogens proved to be equivalent to staff-swabbing in this population in terms of acceptance and pathogen detection.",2012 Nov 14,"['Akmatov, Manas K.', 'Gatzemeier, Anja', 'Schughart, Klaus', 'Pessler, Frank']",PLoS One,,,True
16fb795aec2acb8b86ddac119772abde6392d40f,PMC,Ribosomal frameshifting used in influenza A virus expression occurs within the sequence UCC_UUU_CGU and is in the +1 direction,http://dx.doi.org/10.1098/rsob.120109,PMC3498833,23155484,CC BY,"Programmed ribosomal frameshifting is used in the expression of many virus genes and some cellular genes. In eukaryotic systems, the most well-characterized mechanism involves –1 tandem tRNA slippage on an X_XXY_YYZ motif. By contrast, the mechanisms involved in programmed +1 (or −2) slippage are more varied and often poorly characterized. Recently, a novel gene, PA-X, was discovered in influenza A virus and found to be expressed via a shift to the +1 reading frame. Here, we identify, by mass spectrometric analysis, both the site (UCC_UUU_CGU) and direction (+1) of the frameshifting that is involved in PA-X expression. Related sites are identified in other virus genes that have previously been proposed to be expressed via +1 frameshifting. As these viruses infect insects (chronic bee paralysis virus), plants (fijiviruses and amalgamaviruses) and vertebrates (influenza A virus), such motifs may form a new class of +1 frameshift-inducing sequences that are active in diverse eukaryotes.",2012 Oct,"['Firth, A. E.', 'Jagger, B. W.', 'Wise, H. M.', 'Nelson, C. C.', 'Parsawar, K.', 'Wills, N. M.', 'Napthine, S.', 'Taubenberger, J. K.', 'Digard, P.', 'Atkins, J. F.']",Open Biol,,,True
d014a65d8069ebac6e33bc8bc4dba674151e07d7,PMC,18S rRNA is a reliable normalisation gene for real time PCR based on influenza virus infected cells,http://dx.doi.org/10.1186/1743-422X-9-230,PMC3499178,23043930,CC BY,"BACKGROUND: One requisite of quantitative reverse transcription PCR (qRT-PCR) is to normalise the data with an internal reference gene that is invariant regardless of treatment, such as virus infection. Several studies have found variability in the expression of commonly used housekeeping genes, such as beta-actin (ACTB) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), under different experimental settings. However, ACTB and GAPDH remain widely used in the studies of host gene response to virus infections, including influenza viruses. To date no detailed study has been described that compares the suitability of commonly used housekeeping genes in influenza virus infections. The present study evaluated several commonly used housekeeping genes [ACTB, GAPDH, 18S ribosomal RNA (18S rRNA), ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide (ATP5B) and ATP synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9) (ATP5G1)] to identify the most stably expressed gene in human, pig, chicken and duck cells infected with a range of influenza A virus subtypes. RESULTS: The relative expression stability of commonly used housekeeping genes were determined in primary human bronchial epithelial cells (HBECs), pig tracheal epithelial cells (PTECs), and chicken and duck primary lung-derived cells infected with five influenza A virus subtypes. Analysis of qRT-PCR data from virus and mock infected cells using NormFinder and BestKeeper software programmes found that 18S rRNA was the most stable gene in HBECs, PTECs and avian lung cells. CONCLUSIONS: Based on the presented data from cell culture models (HBECs, PTECs, chicken and duck lung cells) infected with a range of influenza viruses, we found that 18S rRNA is the most stable reference gene for normalising qRT-PCR data. Expression levels of the other housekeeping genes evaluated in this study (including ACTB and GPADH) were highly affected by influenza virus infection and hence are not reliable as reference genes for RNA normalisation.",2012 Oct 8,"['Kuchipudi, Suresh V', 'Tellabati, Meenu', 'Nelli, Rahul K', 'White, Gavin A', 'Perez, Belinda Baquero', 'Sebastian, Sujith', 'Slomka, Marek J', 'Brookes, Sharon M', 'Brown, Ian H', 'Dunham, Stephen P', 'Chang, Kin-Chow']",Virol J,,,True
9fb9a39c7e68fd9c32ab53a6a6ce9af6f1fd2e09,PMC,The Human Cytomegalovirus DNA Polymerase Processivity Factor UL44 Is Modified by SUMO in a DNA-Dependent Manner,http://dx.doi.org/10.1371/journal.pone.0049630,PMC3499415,23166733,CC BY,"During the replication of human cytomegalovirus (HCMV) genome, the viral DNA polymerase subunit UL44 plays a key role, as by binding both DNA and the polymerase catalytic subunit it confers processivity to the holoenzyme. However, several lines of evidence suggest that UL44 might have additional roles during virus life cycle. To shed light on this, we searched for cellular partners of UL44 by yeast two-hybrid screenings. Intriguingly, we discovered the interaction of UL44 with Ubc9, an enzyme involved in the covalent conjugation of SUMO (Small Ubiquitin-related MOdifier) to cellular and viral proteins. We found that UL44 can be extensively sumoylated not only in a cell-free system and in transfected cells, but also in HCMV-infected cells, in which about 50% of the protein resulted to be modified at late times post-infection, when viral genome replication is accomplished. Mass spectrometry studies revealed that UL44 possesses multiple SUMO target sites, located throughout the protein. Remarkably, we observed that binding of UL44 to DNA greatly stimulates its sumoylation both in vitro and in vivo. In addition, we showed that overexpression of SUMO alters the intranuclear distribution of UL44 in HCMV-infected cells, and enhances both virus production and DNA replication, arguing for an important role for sumoylation in HCMV life cycle and UL44 function(s). These data report for the first time the sumoylation of a viral processivity factor and show that there is a functional interplay between the HCMV UL44 protein and the cellular sumoylation system.",2012 Nov 15,"['Sinigalia, Elisa', 'Alvisi, Gualtiero', 'Segré, Chiara V.', 'Mercorelli, Beatrice', 'Muratore, Giulia', 'Winkler, Michael', 'Hsiao, He-Hsuan', 'Urlaub, Henning', 'Ripalti, Alessandro', 'Chiocca, Susanna', 'Palù, Giorgio', 'Loregian, Arianna']",PLoS One,,,True
24e84b0b2c9242ecdddf63700da1454c7aa0efe3,PMC,The Human Cytomegalovirus DNA Polymerase Processivity Factor UL44 Is Modified by SUMO in a DNA-Dependent Manner,http://dx.doi.org/10.1371/journal.pone.0049630,PMC3499415,23166733,CC BY,"During the replication of human cytomegalovirus (HCMV) genome, the viral DNA polymerase subunit UL44 plays a key role, as by binding both DNA and the polymerase catalytic subunit it confers processivity to the holoenzyme. However, several lines of evidence suggest that UL44 might have additional roles during virus life cycle. To shed light on this, we searched for cellular partners of UL44 by yeast two-hybrid screenings. Intriguingly, we discovered the interaction of UL44 with Ubc9, an enzyme involved in the covalent conjugation of SUMO (Small Ubiquitin-related MOdifier) to cellular and viral proteins. We found that UL44 can be extensively sumoylated not only in a cell-free system and in transfected cells, but also in HCMV-infected cells, in which about 50% of the protein resulted to be modified at late times post-infection, when viral genome replication is accomplished. Mass spectrometry studies revealed that UL44 possesses multiple SUMO target sites, located throughout the protein. Remarkably, we observed that binding of UL44 to DNA greatly stimulates its sumoylation both in vitro and in vivo. In addition, we showed that overexpression of SUMO alters the intranuclear distribution of UL44 in HCMV-infected cells, and enhances both virus production and DNA replication, arguing for an important role for sumoylation in HCMV life cycle and UL44 function(s). These data report for the first time the sumoylation of a viral processivity factor and show that there is a functional interplay between the HCMV UL44 protein and the cellular sumoylation system.",2012 Nov 15,"['Sinigalia, Elisa', 'Alvisi, Gualtiero', 'Segré, Chiara V.', 'Mercorelli, Beatrice', 'Muratore, Giulia', 'Winkler, Michael', 'Hsiao, He-Hsuan', 'Urlaub, Henning', 'Ripalti, Alessandro', 'Chiocca, Susanna', 'Palù, Giorgio', 'Loregian, Arianna']",PLoS One,,,False
efa871aeaf22cbd0ce30e8bd1cb3d1afff2a98f9,PMC,Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus,http://dx.doi.org/10.1371/journal.pone.0048702,PMC3499507,23166591,CC BY,"The trans-activator Tat protein is a viral regulatory protein essential for HIV-1 replication. Tat trafficks to the nucleoplasm and the nucleolus. The nucleolus, a highly dynamic and structured membrane-less sub-nuclear compartment, is the site of rRNA and ribosome biogenesis and is involved in numerous cellular functions including transcriptional regulation, cell cycle control and viral infection. Importantly, transient nucleolar trafficking of both Tat and HIV-1 viral transcripts are critical in HIV-1 replication, however, the role(s) of the nucleolus in HIV-1 replication remains unclear. To better understand how the interaction of Tat with the nucleolar machinery contributes to HIV-1 pathogenesis, we investigated the quantitative changes in the composition of the nucleolar proteome of Jurkat T-cells stably expressing HIV-1 Tat fused to a TAP tag. Using an organellar proteomic approach based on mass spectrometry, coupled with Stable Isotope Labelling in Cell culture (SILAC), we quantified 520 proteins, including 49 proteins showing significant changes in abundance in Jurkat T-cell nucleolus upon Tat expression. Numerous proteins exhibiting a fold change were well characterised Tat interactors and/or known to be critical for HIV-1 replication. This suggests that the spatial control and subcellular compartimentaliation of these cellular cofactors by Tat provide an additional layer of control for regulating cellular machinery involved in HIV-1 pathogenesis. Pathway analysis and network reconstruction revealed that Tat expression specifically resulted in the nucleolar enrichment of proteins collectively participating in ribosomal biogenesis, protein homeostasis, metabolic pathways including glycolytic, pentose phosphate, nucleotides and amino acids biosynthetic pathways, stress response, T-cell signaling pathways and genome integrity. We present here the first differential profiling of the nucleolar proteome of T-cells expressing HIV-1 Tat. We discuss how these proteins collectively participate in interconnected networks converging to adapt the nucleolus dynamic activities, which favor host biosynthetic activities and may contribute to create a cellular environment supporting robust HIV-1 production.",2012 Nov 15,"['Jarboui, Mohamed Ali', 'Bidoia, Carlo', 'Woods, Elena', 'Roe, Barbara', 'Wynne, Kieran', 'Elia, Giuliano', 'Hall, William W.', 'Gautier, Virginie W.']",PLoS One,,,True
8597d9f2e677de02b0166ad69f8045b979b3a82a,PMC,Role of Human Sec63 in Modulating the Steady-State Levels of Multi-Spanning Membrane Proteins,http://dx.doi.org/10.1371/journal.pone.0049243,PMC3499540,23166619,CC BY,"The Sec61 translocon of the endoplasmic reticulum (ER) membrane forms an aqueous pore, allowing polypeptides to be transferred across or integrated into membranes. Protein translocation into the ER can occur co- and posttranslationally. In yeast, posttranslational translocation involves the heptameric translocase complex including its Sec62p and Sec63p subunits. The mammalian ER membrane contains orthologs of yeast Sec62p and Sec63p, but their function is poorly understood. Here, we analyzed the effects of excess and deficit Sec63 on various ER cargoes using human cell culture systems. The overexpression of Sec63 reduces the steady-state levels of viral and cellular multi-spanning membrane proteins in a cotranslational mode, while soluble and single-spanning ER reporters are not affected. Consistent with this, the knock-down of Sec63 increases the steady-state pools of polytopic ER proteins, suggesting a substrate-specific and regulatory function of Sec63 in ER import. Overexpressed Sec63 exerts its down-regulating activity on polytopic protein levels independent of its Sec62-interacting motif, indicating that it may not act in conjunction with Sec62 in human cells. The specific action of Sec63 is further sustained by our observations that the up-regulation of either Sec62 or two other ER proteins with lumenal J domains, like ERdj1 and ERdj4, does not compromise the steady-state level of a multi-spanning membrane reporter. A J domain-specific mutation of Sec63, proposed to weaken its interaction with the ER resident BiP chaperone, reduces the down-regulating capacity of excess Sec63, suggesting an involvement of BiP in this process. Together, these results suggest that Sec63 may perform a substrate-selective quantity control function during cotranslational ER import.",2012 Nov 15,"['Mades, Andreas', 'Gotthardt, Katherina', 'Awe, Karin', 'Stieler, Jens', 'Döring, Tatjana', 'Füser, Sabine', 'Prange, Reinhild']",PLoS One,,,True
b09362a1f23af2b6603e7b92b58003b7f9719840,PMC,Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates,http://dx.doi.org/10.1371/journal.pone.0049265,PMC3499546,23166625,CC BY,"Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates. Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown. Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors. In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in these IFITM genes. Significant functional divergence was detected among the three IFITM sub-families. No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation. No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey. The IFITM10 sub-family was divided into two groups: aquatic and terrestrial types. Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups. Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments. A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents. Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.",2012 Nov 15,"['Zhang, Zhao', 'Liu, Jun', 'Li, Meng', 'Yang, Hui', 'Zhang, Chiyu']",PLoS One,,,True
a4b5258ac97a71a862ce4098a819d37bdec19190,PMC,Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates,http://dx.doi.org/10.1371/journal.pone.0049265,PMC3499546,23166625,CC BY,"Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates. Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown. Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors. In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in these IFITM genes. Significant functional divergence was detected among the three IFITM sub-families. No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation. No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey. The IFITM10 sub-family was divided into two groups: aquatic and terrestrial types. Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups. Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments. A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents. Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.",2012 Nov 15,"['Zhang, Zhao', 'Liu, Jun', 'Li, Meng', 'Yang, Hui', 'Zhang, Chiyu']",PLoS One,,,False
b097bead51cf543bb12eff8d3e0b9acbba67c041,PMC,Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates,http://dx.doi.org/10.1371/journal.pone.0049265,PMC3499546,23166625,CC BY,"Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates. Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown. Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors. In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in these IFITM genes. Significant functional divergence was detected among the three IFITM sub-families. No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation. No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey. The IFITM10 sub-family was divided into two groups: aquatic and terrestrial types. Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups. Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments. A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents. Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.",2012 Nov 15,"['Zhang, Zhao', 'Liu, Jun', 'Li, Meng', 'Yang, Hui', 'Zhang, Chiyu']",PLoS One,,,False
ec656117399c96aeb848a626967bf860722bac67,PMC,Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates,http://dx.doi.org/10.1371/journal.pone.0049265,PMC3499546,23166625,CC BY,"Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates. Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown. Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors. In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in these IFITM genes. Significant functional divergence was detected among the three IFITM sub-families. No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation. No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey. The IFITM10 sub-family was divided into two groups: aquatic and terrestrial types. Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups. Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments. A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents. Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.",2012 Nov 15,"['Zhang, Zhao', 'Liu, Jun', 'Li, Meng', 'Yang, Hui', 'Zhang, Chiyu']",PLoS One,,,False
679af2e570eda977721a977e3b542b6cd2eafa09,PMC,Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates,http://dx.doi.org/10.1371/journal.pone.0049265,PMC3499546,23166625,CC BY,"Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates. Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown. Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors. In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in these IFITM genes. Significant functional divergence was detected among the three IFITM sub-families. No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation. No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey. The IFITM10 sub-family was divided into two groups: aquatic and terrestrial types. Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups. Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments. A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents. Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.",2012 Nov 15,"['Zhang, Zhao', 'Liu, Jun', 'Li, Meng', 'Yang, Hui', 'Zhang, Chiyu']",PLoS One,,,False
8d581519c2e082ec871aeb8e6486e3195111b6b7,PMC,Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates,http://dx.doi.org/10.1371/journal.pone.0049265,PMC3499546,23166625,CC BY,"Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates. Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown. Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors. In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in these IFITM genes. Significant functional divergence was detected among the three IFITM sub-families. No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation. No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey. The IFITM10 sub-family was divided into two groups: aquatic and terrestrial types. Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups. Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments. A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents. Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.",2012 Nov 15,"['Zhang, Zhao', 'Liu, Jun', 'Li, Meng', 'Yang, Hui', 'Zhang, Chiyu']",PLoS One,,,False
f353ee74fe20d3333b783fe703231d1313c89303,PMC,Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates,http://dx.doi.org/10.1371/journal.pone.0049265,PMC3499546,23166625,CC BY,"Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates. Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown. Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors. In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in these IFITM genes. Significant functional divergence was detected among the three IFITM sub-families. No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation. No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey. The IFITM10 sub-family was divided into two groups: aquatic and terrestrial types. Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups. Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments. A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents. Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.",2012 Nov 15,"['Zhang, Zhao', 'Liu, Jun', 'Li, Meng', 'Yang, Hui', 'Zhang, Chiyu']",PLoS One,,,False
49e18956b9fad9e6114912a46567cdc6b9555c02,PMC,Current Approaches on Viral Infection: Proteomics and Functional Validations,http://dx.doi.org/10.3389/fmicb.2012.00393,PMC3499792,23162545,CC BY,"Viruses could manipulate cellular machinery to ensure their continuous survival and thus become parasites of living organisms. Delineation of sophisticated host responses upon virus infection is a challenging task. It lies in identifying the repertoire of host factors actively involved in the viral infectious cycle and characterizing host responses qualitatively and quantitatively during viral pathogenesis. Mass spectrometry based proteomics could be used to efficiently study pathogen-host interactions and virus-hijacked cellular signaling pathways. Moreover, direct host and viral responses upon infection could be further investigated by activity-based functional validation studies. These approaches involve drug inhibition of secretory pathway, immunofluorescence staining, dominant negative mutant of protein target, real-time PCR, small interfering siRNA-mediated knockdown, and molecular cloning studies. In this way, functional validation could gain novel insights into the high-content proteomic dataset in an unbiased and comprehensive way.",2012 Nov 16,"['Zheng, Jie', 'Tan, Boon Huan', 'Sugrue, Richard', 'Tang, Kai']",Front Microbiol,,,True
3d1d14a7dc9189add63df0501822830a3291a850,PMC,Genomic Sequences of two Novel Levivirus Single-Stranded RNA Coliphages (Family Leviviridae): Evidence for Recombinationin Environmental Strains,http://dx.doi.org/10.3390/v4091548,PMC3499819,23170172,CC BY,"Bacteriophages are likely the most abundant entities in the aquatic environment, yet knowledge of their ecology is limited. During a fecal source-tracking study, two genetically novel Leviviridae strains were discovered. Although the novel strains were isolated from coastal waters 1130 km apart (North Carolina and Rhode Island, USA), these strains shared 97% nucleotide similarity and 97–100% amino acid similarity. When the novel strains were compared to nine Levivirus genogroup I strains, they shared 95–100% similarity among the maturation, capsid and lysis proteins, but only 84–85% in the RNA-dependent RNA polymerase gene. Further bioinformatic analyses suggested a recombination event occurred. To the best of our knowledge, this is the first description of viral recombinants in environmental Leviviridae ssRNA bacteriophages.",2012 Sep 13,"['Friedman, Stephanie D.', 'Snellgrove, Wyatt C.', 'Genthner, Fred J.']",Viruses,,,True
d806b5203cfba5a87c9a39a25d953572eacf9ab9,PMC,Filovirus Research in Gabon and Equatorial Africa: The Experience of a Research Center in the Heart of Africa,http://dx.doi.org/10.3390/v4091592,PMC3499821,23170174,CC BY,"Health research programs targeting the population of Gabon and Equatorial Africa at the International Center for Medical Research in Franceville (CIRMF), Gabon, have evolved during the years since its inception in 1979 in accordance with emerging diseases. Since the reemergence of Ebola virus in Central Africa, the CIRMF “Emerging Viral Disease Unit” developed diagnostic tools and epidemiologic strategies and transfers of such technology to support the response of the National Public Health System and the World Health Organization to epidemics of Ebola virus disease. The Unit carries out a unique investigation program on the natural history of the filoviruses, emergence of epidemics, and Ebola virus pathogenesis. In addition, academic training is provided at all levels to regional and international students covering emerging conditions (host factors, molecular biology, genetics) that favor the spread of viral diseases.",2012 Sep 13,"['Leroy, Eric', 'Gonzalez, Jean Paul']",Viruses,,,True
c75994b5485339cdf4180bedab58e60366e49740,PMC,Potential Vaccines and Post-Exposure Treatments for Filovirus Infections,http://dx.doi.org/10.3390/v4091619,PMC3499823,23170176,CC BY,"Viruses of the family Filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. While many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. Current progress in the development of filovirus therapeutics and vaccines is outlined herein with respect to their current level of testing, evaluation, and proximity toward human implementation, specifically with regard to human clinical trials, nonhuman primate studies, small animal studies, and in vitro development. Contemporary methods of supportive care and previous treatment approaches for human patients are also discussed.",2012 Sep 21,"['Friedrich, Brian M.', 'Trefry, John C.', 'Biggins, Julia E.', 'Hensley, Lisa E.', 'Honko, Anna N.', 'Smith, Darci R.', 'Olinger, Gene G.']",Viruses,,,True
f4f75af02b7226c5b2363de1a75821a4b9b20412,PMC,Neutralization Interfering Antibodies: A “Novel” Example of Humoral Immune Dysfunction Facilitating Viral Escape?,http://dx.doi.org/10.3390/v4091731,PMC3499828,23170181,CC BY,"The immune response against some viral pathogens, in particular those causing chronic infections, is often ineffective notwithstanding a robust humoral neutralizing response. Several evasion mechanisms capable of subverting the activity of neutralizing antibodies (nAbs) have been described. Among them, the elicitation of non-neutralizing and interfering Abs has been hypothesized. Recently, this evasion mechanism has acquired an increasing interest given its possible impact on novel nAb-based antiviral therapeutic and prophylactic approaches. In this review, we illustrate the mechanisms of Ab-mediated interference and the viral pathogens described in literature as able to adopt this “novel” evasion strategy.",2012 Sep 24,"['Nicasio, Mancini', 'Sautto, Giuseppe', 'Clementi, Nicola', 'Diotti, Roberta A.', 'Criscuolo, Elena', 'Castelli, Matteo', 'Solforosi, Laura', 'Clementi, Massimo', 'Burioni, Roberto']",Viruses,,,True
ab0550f67f34bd6484d7a24b253c8a3e12759b0f,PMC,Reproductive Number and Serial Interval of the First Wave of Influenza A(H1N1)pdm09 Virus in South Africa,http://dx.doi.org/10.1371/journal.pone.0049482,PMC3500305,23166682,CC BY,"BACKGROUND/OBJECTIVE: Describing transmissibility parameters of past pandemics from diverse geographic sites remains critical to planning responses to future outbreaks. We characterize the transmissibility of influenza A(H1N1)pdm09 (hereafter pH1N1) in South Africa during 2009 by estimating the serial interval (SI), the initial effective reproductive number (initial R(t)) and the temporal variation of R(t). METHODS: We make use of data from a central registry of all pH1N1 laboratory-confirmed cases detected throughout South Africa. Whenever date of symptom onset is missing, we estimate it from the date of specimen collection using a multiple imputation approach repeated 100 times for each missing value. We apply a likelihood-based method (method 1) for simultaneous estimation of initial R(t) and the SI; estimate initial R(t) from SI distributions established from prior field studies (method 2); and the Wallinga and Teunis method (method 3) to model the temporal variation of R(t). RESULTS: 12,360 confirmed pH1N1 cases were reported in the central registry. During the period of exponential growth of the epidemic (June 21 to August 3, 2009), we simultaneously estimate a mean R(t) of 1.47 (95% CI: 1.30–1.72) and mean SI of 2.78 days (95% CI: 1.80–3.75) (method 1). Field studies found a mean SI of 2.3 days between primary cases and laboratory-confirmed secondary cases, and 2.7 days when considering both suspected and confirmed secondary cases. Incorporating the SI estimate from field studies using laboratory-confirmed cases, we found an initial R(t) of 1.43 (95% CI: 1.38–1.49) (method 2). The mean R(t) peaked at 2.91 (95% CI: 0.85–2.91) on June 21, as the epidemic commenced, and R(t)>1 was sustained until August 22 (method 3). CONCLUSIONS: Transmissibility characteristics of pH1N1 in South Africa are similar to estimates reported by countries outside of Africa. Estimations using the likelihood-based method are in agreement with field findings.",2012 Nov 16,"['Archer, Brett N.', 'Tempia, Stefano', 'White, Laura F.', 'Pagano, Marcello', 'Cohen, Cheryl']",PLoS One,,,True
4ec1787f65505b0751777ff1f2cb40d13c0d2b96,PMC,On programmed ribosomal frameshifting: the alternative proteomes,http://dx.doi.org/10.3389/fgene.2012.00242,PMC3500957,23181069,CC BY,"Frameshifting results from two main mechanisms: genomic insertions or deletions (indels) or programmed ribosomal frameshifting. Whereas indels can disrupt normal protein function, programmed ribosomal frameshifting can result in dual-coding genes, each of which can produce multiple functional products. Here, I summarize technical advances that have made it possible to identify programmed ribosomal frameshifting events in a systematic way. The results of these studies suggest that such frameshifting occurs in all genomes, and I will discuss methods that could help characterize the resulting alternative proteomes.",2012 Nov 19,"Ketteler, Robin",Front Genet,,,True
aed3656733b0b5c6f2ad8a14ef5e864d468d66da,PMC,Measuring healthcare preparedness: an all-hazards approach,http://dx.doi.org/10.1186/2045-4015-1-42,PMC3502095,23098101,CC BY,"In a paper appearing in this issue, Adini, et al. describe a struggle familiar to many emergency planners—the challenge of planning for all scenarios. The authors contend that all-hazards, or capabilities-based planning, in which a set of core capabilities applicable to numerous types of events is developed, is a more efficient way to achieve general health care system emergency preparedness than scenario-based planning. Essentially, the core of what is necessary to plan for and respond to one kind of disaster (e.g. a biologic event) is also necessary for planning and responding to other types of disasters, allowing for improvements in planning and maximizing efficiencies. While Adini, et al. have advanced the science of health care emergency preparedness through their consideration of 490 measures to assess preparedness, a shorter set of validated preparedness measures would support the dual goals of accountability and improved outcomes and could provide the basis for determining which actions in the name of preparedness really matter.",2012 Oct 25,"['Marcozzi, David E', 'Lurie, Nicole']",Isr J Health Policy Res,,,True
dc014f8a66864512015686665ebbf01c92d8089e,PMC,A cross-sectional study of pandemic influenza health literacy and the effect of a public health campaign,http://dx.doi.org/10.1186/1756-0500-5-377,PMC3502135,22830499,CC BY,"BACKGROUND: To ascertain the understanding of 2009 pandemic (H1N1) influenza and relevant infection control measures in an emergency department population and to assess the effectiveness of education campaigns in informing the public about the pandemic. METHODS: Questionnaires were administered to patients, visitors, non-clinical staff and volunteers. Data were collected on knowledge, preventative measures, information sources, attitudes to government and media reporting, perceived seriousness, behaviour change and intended compliance with future measures. Results were used to construct an overall knowledge score. RESULTS: There were 252 participants. Traditional forms of mass media (138 [55%]) remained the principal information source. Approximately 70% (176) accurately described mode of transmission and recommended precautions and 68% (175) reported behaviour change because of the pandemic. Gaps in knowledge included failure to identify certain high risk groups. Recall of government campaigns was significantly associated with a higher knowledge score. 60% (151) thought that authorities and media had exaggerated the threat; only 40% (101) would comply with recommended measures in a future pandemic. CONCLUSIONS: The knowledge regarding pandemic influenza was high in this population and positively affected by official campaigns. Pandemic planning should address knowledge gaps and the impression that authorities had exaggerated the public-health threat.",2012 Jul 26,"['Jhummon-Mahadnac, Namrata Devi', 'Knott, Jonathan', 'Marshall, Caroline']",BMC Res Notes,,,True
e2309c084ac694227f0411037944e3829c04c777,PMC,Bovine herpes virus type 1 induces apoptosis through Fas-dependent and mitochondria-controlled manner in Madin-Darby bovine kidney cells,http://dx.doi.org/10.1186/1743-422X-9-202,PMC3502331,22978358,CC BY,"BACKGROUND: Bovine herpesvirus type 1 (BHV-1) is an important pathogen in cattle that is responsible for substantial economic losses. Previous studies suggest that BHV-1 may induce apoptosis in Madin-Darby bovine kidney (MDBK) cells via a mechanism only involving caspases and p53. However, the mechanism for BHV-1-induced MDBK cell apoptosis still requires more research. METHODS: MDBK was used as a model to study the precise signaling pathways of apoptosis induced by BHV-1 infection. RESULTS: BHV-1 infection activated a Fas/FasL-mediated apoptotic pathway, resulting in activation of caspase-8 and cleavage of Bid. In addition, BHV-1 infection down-regulated Bcl-2 and up-regulated Bax expression, thereby initiating the release of cytochrome c followed by caspase-9 activation. The combined activation of the extrinsic and intrinsic pathways resulted in activation of downstream effecter caspase-3 and poly ADP-ribose polymerase (PARP), leading to apoptosis. Furthermore, blocking apoptosis using caspase inhibitors improved BHV-1-infected MDBK cell viability to different extent. BHV-1 infection did not induce significant DNA fragmentation in MDBK cells pretreated with ammonium chloride (NH(4)Cl) or cells infected with UV-inactivated BHV-1. Blocking caspases activation increased BHV-1 replication. CONCLUSIONS: BHV-1 induces apoptosis in MDBK cells through extrinsic and intrinsic pathways and there might be cross-talk between the two pathways. In addition, BHV-1 replication may be necessary for the induction of apoptosis in BHV-1-infected cells, and prolonged cell viability benefits BHV-1 replication.",2012 Sep 17,"['Xu, Xingang', 'Zhang, Kuan', 'Huang, Yong', 'Ding, Li', 'Chen, Guangda', 'Zhang, Honglei', 'Tong, Dewen']",Virol J,,,True
1a485fe46f5c18e940782aa60bb756d6ae2a6c0b,PMC,"Influenza Surveillance Among Children With Pneumonia Admitted to a District Hospital in Coastal Kenya, 2007–2010",http://dx.doi.org/10.1093/infdis/jis536,PMC3502370,23169974,CC BY,"Background. Influenza data gaps in sub-Saharan Africa include incidence, case fatality, seasonal patterns, and associations with prevalent disorders. Methods. Nasopharyngeal samples from children aged <12 years who were admitted to Kilifi District Hospital during 2007–2010 with severe or very severe pneumonia and resided in the local demographic surveillance system were screened for influenza A, B, and C viruses by molecular methods. Outpatient children provided comparative data. Results. Of 2002 admissions, influenza A virus infection was diagnosed in 3.5% (71), influenza B virus infection, in 0.9% (19); and influenza C virus infection, in 0.8% (11 of 1404 tested). Four patients with influenza died. Among outpatients, 13 of 331 (3.9%) with acute respiratory infection and 1 of 196 without acute respiratory infection were influenza positive. The annual incidence of severe or very severe pneumonia, of influenza (any type), and of influenza A, was 1321, 60, and 43 cases per 100 000 <5 years of age, respectively. Peak occurrence was in quarters 3–4 each year, and approximately 50% of cases involved infants: temporal association with bacteremia was absent. Hypoxia was more frequent among pneumonia cases involving influenza (odds ratio, 1.78; 95% confidence interval, 1.04–1.96). Influenza A virus subtypes were seasonal H3N2 (57%), seasonal H1N1 (12%), and 2009 pandemic H1N1 (7%). Conclusions. The burden of influenza was small during 2007–2010 in this pediatric hospital in Kenya. Influenza A virus subtype H3N2 predominated, and 2009 pandemic influenza A virus subtype H1N1 had little impact.",2012 Dec 15,"['Onyango, Clayton O.', 'Njeru, Regina', 'Kazungu, Sidi', 'Achilla, Rachel', 'Bulimo, Wallace', 'Welch, Stephen R.', 'Cane, Patricia A.', 'Gunson, Rory N.', 'Hammitt, Laura L.', 'Scott, J. Anthony G.', 'Berkley, James A.', 'Nokes, D. James']",J Infect Dis,,,True
abb624287a5b93c29ec470b38dd4d03b21c8fc34,PMC,Complete genome sequence of an astrovirus identified in a domestic rabbit (Oryctolagus cuniculus) with gastroenteritis,http://dx.doi.org/10.1186/1743-422X-9-216,PMC3502403,22998755,CC BY,"A colony of domestic rabbits in Tennessee, USA, experienced a high-mortality (~90%) outbreak of enterocolitis. The clinical characteristics were one to six days of lethargy, bloating, and diarrhea, followed by death. Heavy intestinal coccidial load was a consistent finding as was mucoid enteropathy with cecal impaction. Preliminary analysis by electron microscopy revealed the presence of virus-like particles in the stool of one of the affected rabbits. Analysis using the Virochip, a viral detection microarray, suggested the presence of an astrovirus, and follow-up PCR and sequence determination revealed a previously uncharacterized member of that family. Metagenomic sequencing enabled the recovery of the complete viral genome, which contains the characteristic attributes of astrovirus genomes. Attempts to propagate the virus in tissue culture have yet to succeed. Although astroviruses cause gastroenteric disease in other mammals, the pathogenicity of this virus and the relationship to this outbreak remains to be determined. This study therefore defines a viral species and a potential rabbit pathogen.",2012 Sep 22,"['Stenglein, Mark D', 'Velazquez, Eric', 'Greenacre, Cheryl', 'Wilkes, Rebecca P', 'Ruby, J Graham', 'Lankton, Julia S', 'Ganem, Donald', 'Kennedy, Melissa A', 'DeRisi, Joseph L']",Virol J,,,True
1f28ddf08dc9bb5b9b4c291f15d3d42ecdf9cde4,PMC,Bioinformatics and evolutionary insight on the spike glycoprotein gene of QX-like and Massachusetts strains of infectious bronchitis virus,http://dx.doi.org/10.1186/1743-422X-9-211,PMC3502414,22992336,CC BY,"BACKGROUND: Infectious bronchitis virus (IBV) is a Gammacoronavirus of the family Coronaviridae and is a causative agent of an economically important disease in poultry. The spike glycoprotein of IBV is essential for host cell attachment, neutralization, and is involved in the induction of protective immunity. Previously obtained sequence data of the spike gene of IBV QX-like and Massachusetts strains were subjected to bioinformatics analysis. FINDINGS: On analysis of potential phosphorylation sites, the Ser542 and Ser563 sites were not present in Massachusetts strains, while QX-like isolates did not have the Ser534 site. Massachusetts and QX-like strains showed different cleavage site motifs. The N-glycosylation sites ASN-XAA-SER/THR-55, 147, 200 and 545 were additionally present in QX-like strains. The leucine-rich repeat regions in Massachusetts strains consisted of stretches of 63 to 69 amino acids, while in the QX-like strains they contained 59 amino acids in length. An additional palmitoylation site was observed in CK/SWE/082066/2010 a QX-like strain. Primary structure data showed difference in the physical properties and hydrophobic nature of both genotypes. The comparison of secondary structures revealed no new structural domains in the genotypic variants. The phylogenetic analyses based on avian and mammalian coronaviruses showed the analysed IBV as closely related to turkey coronaviruses and distantly related to thrush and munia coronaviruses. CONCLUSION: The study demonstrated that spike glycoprotein of the Massachusetts and the QX-like variants of IBV are molecularly distinct and that this may reflect in differences in the behavior of these viruses in vivo.",2012 Sep 19,"['Abro, Shahid Hussain', 'Ullman, Karin', 'Belák, Sándor', 'Baule, Claudia']",Virol J,,,True
b2b90b3519bdcdd02d17595b01c3bb30cb8be63a,PMC,Comparative immunological evaluation of recombinant Salmonella Typhimurium strains expressing model antigens as live oral vaccines,http://dx.doi.org/10.1186/1471-2172-13-54,PMC3503649,23013063,CC BY,"BACKGROUND: Despite the development of various systems to generate live recombinant Salmonella Typhimurium vaccine strains, little work has been performed to systematically evaluate and compare their relative immunogenicity. Such information would provide invaluable guidance for the future rational design of live recombinant Salmonella oral vaccines. RESULT: To compare vaccine strains encoded with different antigen delivery and expression strategies, a series of recombinant Salmonella Typhimurium strains were constructed that expressed either the enhanced green fluorescent protein (EGFP) or a fragment of the hemagglutinin (HA) protein from the H5N1 influenza virus, as model antigens. The antigens were expressed from the chromosome, from high or low-copy plasmids, or encoded on a eukaryotic expression plasmid. Antigens were targeted for expression in either the cytoplasm or the outer membrane. Combinations of strategies were employed to evaluate the efficacy of combined delivery/expression approaches. After investigating in vitro and in vivo antigen expression, growth and infection abilities; the immunogenicity of the constructed recombinant Salmonella strains was evaluated in mice. Using the soluble model antigen EGFP, our results indicated that vaccine strains with high and stable antigen expression exhibited high B cell responses, whilst eukaryotic expression or colonization with good construct stability was critical for T cell responses. For the insoluble model antigen HA, an outer membrane expression strategy induced better B cell and T cell responses than a cytoplasmic strategy. Most notably, the combination of two different expression strategies did not increase the immune response elicited. CONCLUSION: Through systematically evaluating and comparing the immunogenicity of the constructed recombinant Salmonella strains in mice, we identified their respective advantages and deleterious or synergistic effects. Different construction strategies were optimally-required for soluble versus insoluble forms of the protein antigens. If an antigen, such as EGFP, is soluble and expressed at high levels, a low-copy plasmid-cytoplasmic expression strategy is recommended; since it provokes the highest B cell responses and also induces good T cell responses. If a T cell response is preferred, a eukaryotic expression plasmid or a chromosome-based, cytoplasmic-expression strategy is more effective. For insoluble antigens such as HA, an outer membrane expression strategy is recommended.",2012 Sep 26,"['Zheng, Song-yue', 'Yu, Bin', 'Zhang, Ke', 'Chen, Min', 'Hua, Yan-Hong', 'Yuan, Shuofeng', 'Watt, Rory M', 'Zheng, Bo-Jian', 'Yuen, Kwok-Yung', 'Huang, Jian-Dong']",BMC Immunol,,,True
04c80346278c76be38e11fba9ee1a0fccc13c57f,PMC,Candidiasis and other oral mucosal lesions during and after interferon therapy for HCV-related chronic liver diseases,http://dx.doi.org/10.1186/1471-230X-12-155,PMC3503792,23122361,CC BY,"BACKGROUND: Oral lichen planus (OLP) is seen frequently in patients with hepatitis C virus (HCV) infection. The aim of this study was to evaluate the occurrence of oral candidiasis, other mucosal lesions, and xerostomia during interferon (IFN) therapy for HCV infection. METHODS: Of 124 patients with HCV-infected liver diseases treated with IFN therapy in our hospital, 14 (mean age 56.00 ± 12.94 years) who attended to receive administration of IFN once a week were identified and examined for Candida infection and other oral lesions and for the measurement of salivary flow. Serological assays also were carried out. RESULTS: Cultures of Candida from the tongue surfaces were positive in 7 (50.0%) of the 14 patients with HCV infection at least once during IFN therapy. C. albicans was the most common species isolated. The incidence of Candida during treatment with IFN did not increase above that before treatment. Additional oral mucosal lesions were observed in 50.0% (7/14) of patients: OLP in three (21.4%), angular cheilitis in three (21.4%) and recurrent aphthous stomatitis in one (7.1%). OLP occurred in one patient before treatment with IFN, in one during treatment and in one at the end of treatment. 85.7% of the oral lesions were treated with topical steroids. We compared the characteristics of the 7 patients in whom Candida was detected at least once during IFN therapy (group 1) and the 7 patients in whom Candida was not detected during IFN therapy (group 2). The prevalence of oral mucosal lesions (P=0.0075) and incidence of external use of steroids (P=0.0308) in group 1 were significantly higher than in group 2. The average body weight of group 1 decreased significantly compared to group 2 (P=0.0088). Salivary flow decreased in all subjects throughout the course of IFN treatment and returned at 6(th) months after the end of treatment. In group 1, the level of albumin at the beginning of the 6(th) month of IFN administration was lower than in group 2 (P=0.0550). According to multivariate analysis, one factor, the presence of oral mucosal lesions, was associated with the detection of Candida. The adjusted odds ratio for the factor was 36.00 (95% confidence interval 2.68-1485.94). CONCLUSION: We should pay more attention to oral candidiasis as well as other oral mucosal lesions, in patients with weight loss during IFN treatment.",2012 Nov 2,"['Nagao, Yumiko', 'Hashimoto, Kouji', 'Sata, Michio']",BMC Gastroenterol,,,True
697b9d764f13648fa38faa8d93fefde6049d6517,PMC,Human Monoclonal Antibodies against Highly Conserved HR1 and HR2 Domains of the SARS-CoV Spike Protein Are More Broadly Neutralizing,http://dx.doi.org/10.1371/journal.pone.0050366,PMC3503966,23185609,CC BY,"Immune sera from convalescent patients have been shown to be effective in the treatment of patients infected with Severe Acute Respiratory Syndrome Virus (SARS-CoV) making passive immune therapy with human monoclonal antibodies an attractive treatment strategy for SARS. Previously, using Xenomouse (Amgen British Columbia Inc), we produced a panel of neutralizing Human monoclonal antibodies (HmAbs) that could specifically bind to the ectodomain of the SARS-CoV spike (S) glycoprotein. Some of the HmAbs were S1 domain specific, while some were not. In this study, we describe non-S1 binding neutralizing HmAbs that can specifically bind to the conserved S2 domain of the S protein. However, unlike the S1 specific HmAbs, the S2 specific HmAbs can neutralize pseudotyped viruses expressing different S proteins containing receptor binding domain sequences of various clinical isolates. These data indicate that HmAbs which bind to conserved regions of the S protein are more suitable for conferring protection against a wide range of SARS-CoV variants and have implications for generating therapeutic antibodies or subunit vaccines against other enveloped viruses.",2012 Nov 21,"['Elshabrawy, Hatem A.', 'Coughlin, Melissa M.', 'Baker, Susan C.', 'Prabhakar, Bellur S.']",PLoS One,,,True
0cc12d028d0f63383a4243bb73d76f70ae229daa,PMC,Identification of a Conserved B-cell Epitope on Reticuloendotheliosis Virus Envelope Protein by Screening a Phage-displayed Random Peptide Library,http://dx.doi.org/10.1371/journal.pone.0049842,PMC3504085,23185456,CC BY,"BACKGROUND: The gp90 protein of avian reticuloendotheliosis-associated virus (REV-A) is an important envelope glycoprotein, which is responsible for inducing protective antibody immune responses in animals. B-cell epitopes on the gp90 protein of REV have not been well studied and reported. METHODS AND RESULTS: This study describes the identification of a linear B-cell epitope on the gp90 protein by screening a phage-displayed 12-mer random peptide library with the neutralizing monoclonal antibody (mAb) A9E8 directed against the gp90. The mAb A9E8 recognized phages displaying peptides with the consensus motif SVQYHPL. Amino acid sequence of the motif exactly matched (213)SVQYHPL(219) of the gp90. Further identification of the displayed B cell epitope was conducted using a set of truncated peptides expressed as GST fusion proteins and the Western blot results indicated that (213)SVQYHPL(219) was the minimal determinant of the linear B cell epitope recognized by the mAb A9E8. Moreover, an eight amino acid peptide SVQYHPLA was proven to be the minimal unit of the epitope with the maximal binding activity to mAb A9E8. The REV-A-positive chicken serum reacted with the minimal linear epitopes in Western blot, revealing the importance of the eight amino acids of the epitope in antibody-epitope binding activity. Furthermore, we found that the epitope is a common motif shared among REV-A and other members of REV group. CONCLUSIONS AND SIGNIFICANCE: We identified (213)SVQYHPL(219) as a gp90-specific linear B-cell epitope recognized by the neutralizing mAb A9E8. The results in this study may have potential applications in development of diagnostic techniques and epitope-based marker vaccines against REV-A and other viruses of the REV group.",2012 Nov 21,"['Xue, Mei', 'Shi, Xingming', 'Zhang, Jing', 'Zhao, Yan', 'Cui, Hongyu', 'Hu, Shunlei', 'Gao, Hongbo', 'Cui, Xianlan', 'Wang, Yun-Feng']",PLoS One,,,True
17752cd197628ca49a7b800528bdd68532e4a148,PMC,Ezrin Interacts with the SARS Coronavirus Spike Protein and Restrains Infection at the Entry Stage,http://dx.doi.org/10.1371/journal.pone.0049566,PMC3504146,23185364,CC BY,"BACKGROUND: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. METHODOLOGY/PRINCIPAL FINDINGS: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S-pseudotyped particles and potentiated S-dependent membrane fusion. CONCLUSIONS/SIGNIFICANCE: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.",2012 Nov 21,"['Millet, Jean Kaoru', 'Kien, François', 'Cheung, Chung-Yan', 'Siu, Yu-Lam', 'Chan, Wing-Lim', 'Li, Huiying', 'Leung, Hiu-Lan', 'Jaume, Martial', 'Bruzzone, Roberto', 'Malik Peiris, Joseph S.', 'Altmeyer, Ralf Marius', 'Nal, Béatrice']",PLoS One,,,True
6bc785e1a4016681657922ea713cb52b1c30e655,PMC,Lower Respiratory Tract Infection in a Renal Transplant Recipient: Do not Forget Metapneumovirus,http://dx.doi.org/10.1155/2012/353871,PMC3505633,23213611,CC BY,"Human metapneumovirus (hMPV) is emerging as a cause of a severe respiratory tract infection in immunocompromised patients. hMPV pneumonia has only been seldom reported in nonpulmonary solid organ transplanted patients, such as renal transplant recipients. We report here a case of a 39-year-old patient presenting with fever, cough, and interstitial opacities on CT scan diagnosed as a nonsevere hMPV pneumonia 11 years after a renal transplantation. Infection resolved spontaneously. Differential diagnosis with Pneumocystis pneumonia was discussed. We review the medical literature and discuss clinical presentation and detection methods that can be proposed in solid organ transplant recipients.",2012 Nov 14,"['Noel, N.', 'Rammaert, B.', 'Zuber, J.', 'Sayre, N.', 'Mamzer-Bruneel, M. F.', 'Leruez-Ville, M.', 'Mascard, L.', 'Lecuit, M.', 'Lortholary, O.']",Case Rep Transplant,,,True
05ce1f7ae3a2051067e57e5e52f9cdad0e26a187,PMC,The ORF2 glycoprotein of hepatitis E virus inhibits cellular NF-κB activity by blocking ubiquitination mediated proteasomal degradation of IκBα in human hepatoma cells,http://dx.doi.org/10.1186/1471-2091-13-7,PMC3506457,22590978,CC BY,"BACKGROUND: Nuclear factor kappa B (NF-κB) is a key transcription factor that plays a crucial role in host survival during infection by pathogens. Therefore, it has been a priority of many pathogens to manipulate the cellular NF-κB activity in order to create a favorable environment for their survival inside the host. RESULTS: We observed that heterologous expression of the open reading frame 2 (ORF2) protein in human hepatoma cells led to stabilization of the cellular I kappa B alpha (IκBα) pool, with a concomitant reduction in the nuclear localization of the p65 subunit of NF-κB and inhibition of NF-κB activity. Although basal or TPA induced phosphorylation of IκBα was not altered, its ubiquitination was markedly reduced in ORF2 expressing cells. Further analysis revealed that ORF2 protein could directly associate with the F-box protein, beta transducin repeat containing protein (βTRCP) and ORF2 over expression resulted in reduced association of IκBα with the SKP1 and CUL1 components of the SCF(βTRCP) complex. Chromatin immunoprecipitation (ChIP) assay of the proximal promoter regions of MHC-I heavy chain and IL-8 genes using p65 antibody and LPS stimulated ORF2 expressing cell extract revealed decreased association of p65 with the above regions, indicating that ORF2 inhibited p65 binding at endogenous promoters. CONCLUSIONS: In this report we suggest a mechanism by which ORF2 protein of HEV may inhibit host cell NF-κB activity during the course of a viral infection.",2012 May 16,"['Varshney, Bhavna', 'Lal, Sunil K']",BMC Biochem,,,True
434bd9335384207d750282844ad8ceb545e50462,PMC,Performance of LBSap Vaccine after Intradermal Challenge with L. infantum and Saliva of Lu. longipalpis: Immunogenicity and Parasitological Evaluation,http://dx.doi.org/10.1371/journal.pone.0049780,PMC3506642,23189161,CC BY,"In the last decade, the search for new vaccines against canine visceral leishmaniasis has intensified. However, the pattern related to immune protection during long periods after experimental infection in vaccine trials is still not fully understood. Herein, we investigated the immunogenicity and parasitological levels after intradermal challenge with Leishmania infantum plus salivary gland extract in dogs immunized with a vaccine composed of L. braziliensis antigens plus saponin as an adjuvant (LBSap vaccine). The LBSap vaccine elicited higher levels of total anti-Leishmania IgG as well as both IgG1 and IgG2. Furthermore, dogs vaccinated had increased levels of lymphocytes, particularly circulating B cells (CD21(+)) and both CD4(+) and CD8(+) T lymphocytes. LBSap also elicited an intense in vitro cell proliferation associated with higher levels of CD4(+) T lymphocytes specific for vaccine soluble antigen and soluble lysate of L. infantum antigen even 885 days after experimental challenge. Furthermore, LBSap vaccinated dogs presented high IFN-γ and low IL-10 and TGF-β1 expression in spleen with significant reduction of parasite load in this tissue. Overall, our results validate the potential of LBSap vaccine to protect against L. infantum experimental infection and strongly support further evaluation of efficiency of LBSap against CVL in natural infection conditions.",2012 Nov 26,"['Roatt, Bruno Mendes', 'Aguiar-Soares, Rodrigo Dian de Oliveira', 'Vitoriano-Souza, Juliana', 'Coura-Vital, Wendel', 'Braga, Samuel Leôncio', 'Corrêa-Oliveira, Rodrigo', 'Martins-Filho, Olindo Assis', 'Teixeira-Carvalho, Andréa', 'de Lana, Marta', 'Gontijo, Nelder Figueiredo', 'Marques, Marcos José', 'Giunchetti, Rodolfo Cordeiro', 'Reis, Alexandre Barbosa']",PLoS One,,,True
e53306862eb2cab646ba36a1e685fdb5a392da42,PMC,A new look at an old virus: patterns of mutation accumulation in the human H1N1 influenza virus since 1918,http://dx.doi.org/10.1186/1742-4682-9-42,PMC3507676,23062055,CC BY,"BACKGROUND: The H1N1 influenza A virus has been circulating in the human population for over 95 years, first manifesting itself in the pandemic of 1917–1918. Initial mortality was extremely high, but dropped exponentially over time. Influenza viruses have high mutation rates, and H1N1 has undergone significant genetic changes since 1918. The exact nature of H1N1 mutation accumulation over time has not been fully explored. METHODS: We have made a comprehensive historical analysis of mutational changes within H1N1 by examining over 4100 fully-sequenced H1N1 genomes. This has allowed us to examine the genetic changes arising within H1N1 from 1918 to the present. RESULTS: We document multiple extinction events, including the previously known extinction of the human H1N1 lineage in the 1950s, and an apparent second extinction of the human H1N1 lineage in 2009. These extinctions appear to be due to a continuous accumulation of mutations. At the time of its disappearance in 2009, the human H1N1 lineage had accumulated over 1400 point mutations (more than 10% of the genome), including approximately 330 non-synonymous changes (7.4% of all codons). The accumulation of both point mutations and non-synonymous amino acid changes occurred at constant rates (μ = 14.4 and 2.4 new mutations/year, respectively), and mutations accumulated uniformly across the entire influenza genome. We observed a continuous erosion over time of codon-specificity in H1N1, including a shift away from host (human, swine, and bird [duck]) codon preference patterns. CONCLUSIONS: While there have been numerous adaptations within the H1N1 genome, most of the genetic changes we document here appear to be non-adaptive, and much of the change appears to be degenerative. We suggest H1N1 has been undergoing natural genetic attenuation, and that significant attenuation may even occur during a single pandemic. This process may play a role in natural pandemic cessation and has apparently contributed to the exponential decline in mortality rates over time, as seen in all major human influenza strains. These findings may be relevant to the development of strategies for managing influenza pandemics and strain evolution.",2012 Oct 12,"['Carter, Robert W', 'Sanford, John C']",Theor Biol Med Model,,,True
4ed134293562340d043a5e0b6f5d822df7cf7079,PMC,"Functional repertoire, molecular pathways and diseases associated with 3D domain swapping in the human proteome",http://dx.doi.org/10.1186/2043-9113-2-8,PMC3508620,22472218,CC BY,"BACKGROUND: 3D domain swapping is a novel structural phenomenon observed in diverse set of protein structures in oligomeric conformations. A distinct structural feature, where structural segments in a protein dimer or higher oligomer were shared between two or more chains of a protein structure, characterizes 3D domain swapping. 3D domain swapping was observed as a key mediator of numerous functional mechanisms and play pathogenic role in various diseases including conformational diseases like amyloidosis, Alzheimer's disease, Parkinson's disease and prion diseases. We report the first study with a focus on identifying functional classes, pathways and diseases mediated by 3D domain swapping in the human proteome. METHODS: We used a panel of four enrichment tools with two different ontologies and two annotations database to derive biological and clinical relevant information associated with 3D domain swapping. Protein domain enrichment analysis followed by Gene Ontology (GO) term enrichment analysis revealed the functional repertoire of proteins involved in swapping. Pathway analysis using KEGG annotations revealed diverse pathway associations of human proteins involved in 3D domain swapping. Disease Ontology was used to find statistically significant associations with proteins in swapped conformation and various disease categories (P-value < 0.05). RESULTS: We report meta-analysis results of a literature-curated dataset of human gene products involved in 3D domain swapping and discuss new insights about the functional repertoire, pathway associations and disease implications of proteins involved in 3D domain swapping. CONCLUSIONS: Our integrated bioinformatics pipeline comprising of four different enrichment tools, two ontologies and two annotations revealed new insights into the functional and disease correlations with 3D domain swapping. GO term enrichment were used to infer terms associated with three different GO categories. Protein domain enrichment was used to identify conserved domains enriched in swapped proteins. Pathway enrichment analysis using KEGG annotations revealed that proteins with swapped conformations are present in all six classes of KEGG BRITE hierarchy and significantly enriched KEGG pathways were observed in five classes. Five major classes of disease were found to be associated with 3D domain swapping using functional disease ontology based enrichment analysis. Five classes of human diseases: cancer, diseases of the respiratory or pulmonary system, degenerative diseases of the central nervous system, vascular disease and encephalitis were found to be significant. In conclusion, our study shows that bioinformatics based analytical approaches using curated data can enhance the understanding of functional and disease implications of 3D domain swapping.",2012 Apr 3,"['Shameer, Khader', 'Sowdhamini, Ramanathan']",J Clin Bioinforma,,,True
4d4de01a6f9ad02ac0939d54713c209153fa66df,PMC,Development and evaluation of an immunochromatographic strip for rapid detection of porcine hemagglutinating encephalomyelitis virus,http://dx.doi.org/10.1186/1743-422X-9-172,PMC3508965,22920192,CC BY,"BACKGROUND: The incidence of PHE among pigs in many countries is on the rise, and it has caused great economic losses to the pig industry. Therefore, the development of a sensitive, specific, and easily-performed assay is crucial for the rapid detection and surveillance of PHE-CoV infection and transmission. RESULTS: An immunochromatographic strip was developed for the detection of PHE-CoV. The colloidal gold-labeled MAb 4D4 was used as the detection reagent, and the MAb 1E2 and goat anti-mouse IgG coated the strip's test and control lines, respectively. The immunochromatographic strip was capable of specifically detecting PHE-CoV with a HA unit of 2 within 10 min. Storage of the strips at room temperature for 6 months or at 4°C for 12 months did not change their sensitivity or specificity. Using RT-PCR as a reference test, the relative specificity and sensitivity of the immunochromatographic strip were determined to be 100% and 97.78%, respectively. There was an excellent agreement between the results obtained by RT-PCR and the immunochromatographic strips (kappa = 0.976). Additionally, there was a strong agreement between the sandwich enzyme-linked immunosorbent assay (ELISA) and immunochromatographic strips (Kappa = 0.976). When the immunochromatographic strips were used for diagnosing PHE-CoV infection in the Jilin Province, the PHE-CoV-positive rate ranged from 61.54% in the Jilin district to 17.95% in the Songyuan district. CONCLUSIONS: Based on its high specificity, sensitivity, and stability, the immunochromatographic strip would be suitable for on-site detection of PHE-CoV for surveillance and epidemiological purposes.",2012 Aug 24,"['Chen, Keyan', 'Zhao, Kui', 'Song, Deguang', 'He, Wenqi', 'Gao, Wei', 'Zhao, Chuanbo', 'Wang, Chengli', 'Gao, Feng']",Virol J,,,True
8a8463146cf8f61c2d62df2adaa251adbe2f9dc1,PMC,"Burden of influenza, healthcare seeking behaviour and hygiene measures during the A(H1N1)2009 pandemic in France: a population based study",http://dx.doi.org/10.1186/1471-2458-12-947,PMC3508974,23127166,CC BY,"BACKGROUND: Influenza surveillance systems do not allow the identification of the true burden of illness caused by influenza in the community because they are restricted to consulting cases. A study was conducted to estimate the incidence and the burden of self-defined influenza, and to describe healthcare seeking behavior for self-defined influenza during the A(H1N1)2009 pandemic in the French population. METHODS: We conducted a random-based retrospective cross-sectional telephone survey between May 2009 and April 2010 among a random sample of the French population. RESULTS: For the 10 076 people included, 107 episodes of self-defined influenza were reported. The annual incidence of self-defined influenza was estimated at 13 942 cases per 100 000 inhabitants (CI95% 10 947 – 16 961), 62.1% (CI95% 50.5 – 72.5) of cases consulted a physician and 11.3% (CI95% 5.5 - 21.7) used a face mask. Following recommendations, 37.5% (CI95% 35.5 – 39.5) of people in the survey reported washing their hands more often during the pandemic season, and there was a positive association with being vaccinated against A(H1N1)2009 influenza, being a women, being a child (< 15 years) or living in a big city (≥ 100 000 inhabitants). CONCLUSIONS: Self-defined influenza causes a significant burden of illness in the French population and is a frequent cause for consultation. These results allow a more accurate interpretation of influenza surveillance data and an opportunity to adapt future health education messages.",2012 Nov 5,"['Van Cauteren, Dieter', 'Vaux, Sophie', 'de Valk, Henriette', 'Le Strat, Yann', 'Vaillant, Véronique', 'Lévy-Bruhl, Daniel']",BMC Public Health,,,True
df51bfb59565119816648b8f02f5a4f25ee4a76c,PMC,Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator,http://dx.doi.org/10.1186/1471-2458-12-870,PMC3509032,23061807,CC BY,"BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.",2012 Oct 12,"['Stein, Mart Lambertus', 'Rudge, James W', 'Coker, Richard', 'van der Weijden, Charlie', 'Krumkamp, Ralf', 'Hanvoravongchai, Piya', 'Chavez, Irwin', 'Putthasri, Weerasak', 'Phommasack, Bounlay', 'Adisasmito, Wiku', 'Touch, Sok', 'Sat, Le Minh', 'Hsu, Yu-Chen', 'Kretzschmar, Mirjam', 'Timen, Aura']",BMC Public Health,,,True
98ebefa9ea63cabfcfac33fb259adf77a19428af,PMC,Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator,http://dx.doi.org/10.1186/1471-2458-12-870,PMC3509032,23061807,CC BY,"BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.",2012 Oct 12,"['Stein, Mart Lambertus', 'Rudge, James W', 'Coker, Richard', 'van der Weijden, Charlie', 'Krumkamp, Ralf', 'Hanvoravongchai, Piya', 'Chavez, Irwin', 'Putthasri, Weerasak', 'Phommasack, Bounlay', 'Adisasmito, Wiku', 'Touch, Sok', 'Sat, Le Minh', 'Hsu, Yu-Chen', 'Kretzschmar, Mirjam', 'Timen, Aura']",BMC Public Health,,,True
d8714feba6d9a8670db5d8e4d998a3de95d16a3c,PMC,Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator,http://dx.doi.org/10.1186/1471-2458-12-870,PMC3509032,23061807,CC BY,"BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.",2012 Oct 12,"['Stein, Mart Lambertus', 'Rudge, James W', 'Coker, Richard', 'van der Weijden, Charlie', 'Krumkamp, Ralf', 'Hanvoravongchai, Piya', 'Chavez, Irwin', 'Putthasri, Weerasak', 'Phommasack, Bounlay', 'Adisasmito, Wiku', 'Touch, Sok', 'Sat, Le Minh', 'Hsu, Yu-Chen', 'Kretzschmar, Mirjam', 'Timen, Aura']",BMC Public Health,,,True
dd40b192bbddb785dd3f6e42e45853cd4b14cdca,PMC,Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator,http://dx.doi.org/10.1186/1471-2458-12-870,PMC3509032,23061807,CC BY,"BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.",2012 Oct 12,"['Stein, Mart Lambertus', 'Rudge, James W', 'Coker, Richard', 'van der Weijden, Charlie', 'Krumkamp, Ralf', 'Hanvoravongchai, Piya', 'Chavez, Irwin', 'Putthasri, Weerasak', 'Phommasack, Bounlay', 'Adisasmito, Wiku', 'Touch, Sok', 'Sat, Le Minh', 'Hsu, Yu-Chen', 'Kretzschmar, Mirjam', 'Timen, Aura']",BMC Public Health,,,True
323975b3348556eb9cf84e82ffcc51de563d1379,PMC,Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator,http://dx.doi.org/10.1186/1471-2458-12-870,PMC3509032,23061807,CC BY,"BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.",2012 Oct 12,"['Stein, Mart Lambertus', 'Rudge, James W', 'Coker, Richard', 'van der Weijden, Charlie', 'Krumkamp, Ralf', 'Hanvoravongchai, Piya', 'Chavez, Irwin', 'Putthasri, Weerasak', 'Phommasack, Bounlay', 'Adisasmito, Wiku', 'Touch, Sok', 'Sat, Le Minh', 'Hsu, Yu-Chen', 'Kretzschmar, Mirjam', 'Timen, Aura']",BMC Public Health,,,False
48cc713567a278caa4b15e0528e1babe71efe44c,PMC,Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator,http://dx.doi.org/10.1186/1471-2458-12-870,PMC3509032,23061807,CC BY,"BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.",2012 Oct 12,"['Stein, Mart Lambertus', 'Rudge, James W', 'Coker, Richard', 'van der Weijden, Charlie', 'Krumkamp, Ralf', 'Hanvoravongchai, Piya', 'Chavez, Irwin', 'Putthasri, Weerasak', 'Phommasack, Bounlay', 'Adisasmito, Wiku', 'Touch, Sok', 'Sat, Le Minh', 'Hsu, Yu-Chen', 'Kretzschmar, Mirjam', 'Timen, Aura']",BMC Public Health,,,True
dfe39ec7e5950a8ca7d5e0d1a503176f0fc824c2,PMC,Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator,http://dx.doi.org/10.1186/1471-2458-12-870,PMC3509032,23061807,CC BY,"BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.",2012 Oct 12,"['Stein, Mart Lambertus', 'Rudge, James W', 'Coker, Richard', 'van der Weijden, Charlie', 'Krumkamp, Ralf', 'Hanvoravongchai, Piya', 'Chavez, Irwin', 'Putthasri, Weerasak', 'Phommasack, Bounlay', 'Adisasmito, Wiku', 'Touch, Sok', 'Sat, Le Minh', 'Hsu, Yu-Chen', 'Kretzschmar, Mirjam', 'Timen, Aura']",BMC Public Health,,,False
699369c8d371b09fca7aeb53e54b3b569e1653d0,PMC,What was the primary mode of smallpox transmission? Implications for biodefense,http://dx.doi.org/10.3389/fcimb.2012.00150,PMC3509329,23226686,CC BY,"The mode of infection transmission has profound implications for effective containment by public health interventions. The mode of smallpox transmission was never conclusively established. Although, “respiratory droplet” transmission was generally regarded as the primary mode of transmission, the relative importance of large ballistic droplets and fine particle aerosols that remain suspended in air for more than a few seconds was never resolved. This review examines evidence from the history of variolation, data on mucosal infection collected in the last decades of smallpox transmission, aerosol measurements, animal models, reports of smallpox lung among healthcare workers, and the epidemiology of smallpox regarding the potential importance of fine particle aerosol mediated transmission. I introduce briefly the term anisotropic infection to describe the behavior of Variola major in which route of infection appears to have altered the severity of disease.",2012 Nov 29,"Milton, Donald K.",Front Cell Infect Microbiol,,,True
3c44fe859327f5e7b02cc27a10a228ae5288d65b,PMC,Comparative Genomics of Korean Infectious Bronchitis Viruses (IBVs) and an Animal Model to Evaluate Pathogenicity of IBVs to the Reproductive Organs,http://dx.doi.org/10.3390/v4112670,PMC3509667,23202499,CC BY,"The K-I and nephropathogenic K-II genotypes of infectious bronchitis virus (IBV) have been isolated since 1995 and 1990, respectively, in Korea and commercial inactivated oil-emulsion vaccines containing KM91 (K-II type) and Massachusetts 41 strains have been used in the field. To date, genomic analyses of Korean IBV strains and animal models to test the pathogenicity of Korean IBVs to the reproductive organs have been rare. In the present study, comparative genomics of SNU8067 (K-I type) and KM91 IBVs was performed, and an animal model to test the pathogenicity of SNU8067 was established and applied to vaccine efficacy test. The genome sizes of SNU8067 (27,708 nt) and KM91 (27,626 nt) were slightly different and the nucleotide and amino acid identities of the S1 (79%, 77%), 3a (65%, 52%), and 3b (81%, 72%) genes were lower than those of other genes (94%–97%, 92%–98%). A recombination analysis revealed that SNU8067 was a recombinant virus with a KM91-like backbone except S1, 3a, and 3b genes which might be from an unknown virus. An SNU8067 infection inhibited formation of hierarchal ovarian follicles (80%) and oviduct maturation (50%) in the control group, whereas 70% of vaccinated chickens were protected from lesions.",2012 Oct 30,"['Hong, Seung-Min', 'Kwon, Hyuk-Joon', 'Kim, Il-Hwan', 'Mo, Mei-Lan', 'Kim, Jae-Hong']",Viruses,,,True
59ac4eae51d6084c2346ebd27125a3b56e25d72e,PMC,Clinical Aspects of Feline Retroviruses: A Review,http://dx.doi.org/10.3390/v4112684,PMC3509668,23202500,CC BY,"Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia), and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less commonly diagnosed than in the previous 20 years; prevalence has been decreasing in most countries. However, FeLV importance may be underestimated as it has been shown that regressively infected cats (that are negative in routinely used FeLV tests) also can develop clinical signs. FIV can cause an acquired immunodeficiency syndrome that increases the risk of opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. This article provides a review of clinical syndromes in progressively and regressively FeLV-infected cats as well as in FIV-infected cats.",2012 Oct 31,"Hartmann, Katrin",Viruses,,,True
b0dcc756c7f2641a8319b96355ec871ba2922f90,PMC,"Use of an Innovative Web-Based Laboratory Surveillance Platform to Analyze Mixed Infections Between Human Metapneumovirus (hMPV) and Other Respiratory Viruses Circulating in Alberta (AB), Canada (2009–2012)",http://dx.doi.org/10.3390/v4112754,PMC3509671,23202503,CC BY,"We investigated the proportions of mono vs. mixed infections for human metapneumovirus (hMPV) as compared to adenovirus (ADV), four types of coronavirus (CRV), parainfluenza virus (PIV), RSV, and enterovirus/rhinovirus (ERV) in Alberta, Canada. Using the Data Integration for Alberta Laboratories (DIAL) platform, 26,226 respiratory specimens at ProvLab between 1 July 2009 and 30 June 2012 were selected and included in the study. Using the Respiratory Virus Panel these specimens tested positive for one or more respiratory virus and negative for influenza A and B. From our subset hMPV was the fourth most common virus (n=2,561) with 373 (15%) identified as mixed infection using DIAL. Mixed infection with hMPV was most commonly found in infants less than 6 months old and ERV was most commonly found in mixed infection with hMPV (230/373, 56%) across all age groups. The proportion of mixed-infection vs. mono-infection was highest for ADV (46%), followed by CRV 229E (32%), CRV HKU1 (31%), CRV NL63 (28%), CRV OC43 (23%), PIV (20%), RSV (17%), hMPV (15%) and ERV (13%). hMPV was significantly more likely to be identified in mono infection as compared with ADV, CRV, PIV, and RSV with the exception of ERV [p<0.05].",2012 Nov 5,"['Fathima, Sumana', 'Lee, Bonita E.', 'May-Hadford, Jennifer', 'Mukhi, Shamir', 'Drews, Steven J.']",Viruses,,,True
54447606d747c1bb9865d1b344bdd8ad0e200bf0,PMC,The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis,http://dx.doi.org/10.3390/v4112902,PMC3509677,23202509,CC BY,"A respiratory disease caused by a novel coronavirus, termed the severe acute respiratory syndrome coronavirus (SARS-CoV), was first reported in China in late 2002. The subsequent efficient human-to-human transmission of this virus eventually affected more than 30 countries worldwide, resulting in a mortality rate of ~10% of infected individuals. The spread of the virus was ultimately controlled by isolation of infected individuals and there has been no infections reported since April 2004. However, the natural reservoir of the virus was never identified and it is not known if this virus will re-emerge and, therefore, research on this virus continues. The SARS-CoV genome is about 30 kb in length and is predicted to contain 14 functional open reading frames (ORFs). The genome encodes for proteins that are homologous to known coronavirus proteins, such as the replicase proteins (ORFs 1a and 1b) and the four major structural proteins: nucleocapsid (N), spike (S), membrane (M) and envelope (E). SARS-CoV also encodes for eight unique proteins, called accessory proteins, with no known homologues. This review will summarize the current knowledge on SARS-CoV accessory proteins and will include: (i) expression and processing; (ii) the effects on cellular processes; and (iii) functional studies.",2012 Nov 7,"['McBride, Ruth', 'Fielding, Burtram C.']",Viruses,,,True
d171f82b892a2afafc2bc8a5458219dc04c8fd8d,PMC,Human Coronaviruses: Insights into Environmental Resistance and Its Influence on the Development of New Antiseptic Strategies,http://dx.doi.org/10.3390/v4113044,PMC3509683,23202515,CC BY,"The Coronaviridae family, an enveloped RNA virus family, and, more particularly, human coronaviruses (HCoV), were historically known to be responsible for a large portion of common colds and other upper respiratory tract infections. HCoV are now known to be involved in more serious respiratory diseases, i.e. bronchitis, bronchiolitis or pneumonia, especially in young children and neonates, elderly people and immunosuppressed patients. They have also been involved in nosocomial viral infections. In 2002–2003, the outbreak of severe acute respiratory syndrome (SARS), due to a newly discovered coronavirus, the SARS-associated coronavirus (SARS-CoV); led to a new awareness of the medical importance of the Coronaviridae family. This pathogen, responsible for an emerging disease in humans, with high risk of fatal outcome; underline the pressing need for new approaches to the management of the infection, and primarily to its prevention. Another interesting feature of coronaviruses is their potential environmental resistance, despite the accepted fragility of enveloped viruses. Indeed, several studies have described the ability of HCoVs (i.e. HCoV 229E, HCoV OC43 (also known as betacoronavirus 1), NL63, HKU1 or SARS-CoV) to survive in different environmental conditions (e.g. temperature and humidity), on different supports found in hospital settings such as aluminum, sterile sponges or latex surgical gloves or in biological fluids. Finally, taking into account the persisting lack of specific antiviral treatments (there is, in fact, no specific treatment available to fight coronaviruses infections), the Coronaviridae specificities (i.e. pathogenicity, potential environmental resistance) make them a challenging model for the development of efficient means of prevention, as an adapted antisepsis-disinfection, to prevent the environmental spread of such infective agents. This review will summarize current knowledge on the capacity of human coronaviruses to survive in the environment and the efficacy of well-known antiseptic-disinfectants against them, with particular focus on the development of new methodologies to evaluate the activity of new antiseptic-disinfectants on viruses.",2012 Nov 12,"['Geller, Chloé', 'Varbanov, Mihayl', 'Duval, Raphaël E.']",Viruses,,,True
9680a6922144725138edc920dbf6c3dc48e822b6,PMC,Virus Pathogen Database and Analysis Resource (ViPR): A Comprehensive Bioinformatics Database and Analysis Resource for the Coronavirus Research Community,http://dx.doi.org/10.3390/v4113209,PMC3509690,23202522,CC BY,"Several viruses within the Coronaviridae family have been categorized as either emerging or re-emerging human pathogens, with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) being the most well known. The NIAID-sponsored Virus Pathogen Database and Analysis Resource (ViPR, www.viprbrc.org) supports bioinformatics workflows for a broad range of human virus pathogens and other related viruses, including the entire Coronaviridae family. ViPR provides access to sequence records, gene and protein annotations, immune epitopes, 3D structures, host factor data, and other data types through an intuitive web-based search interface. Records returned from these queries can then be subjected to web-based analyses including: multiple sequence alignment, phylogenetic inference, sequence variation determination, BLAST comparison, and metadata-driven comparative genomics statistical analysis. Additional tools exist to display multiple sequence alignments, view phylogenetic trees, visualize 3D protein structures, transfer existing reference genome annotations to new genomes, and store or share results from any search or analysis within personal private ‘Workbench’ spaces for future access. All of the data and integrated analysis and visualization tools in ViPR are made available without charge as a service to the Coronaviridae research community to facilitate the research and development of diagnostics, prophylactics, vaccines and therapeutics against these human pathogens.",2012 Nov 19,"['Pickett, Brett E.', 'Greer, Douglas S.', 'Zhang, Yun', 'Stewart, Lucy', 'Zhou, Liwei', 'Sun, Guangyu', 'Gu, Zhiping', 'Kumar, Sanjeev', 'Zaremba, Sam', 'Larsen, Christopher N.', 'Jen, Wei', 'Klem, Edward B.', 'Scheuermann, Richard H.']",Viruses,,,True
8791721a89fa47907acb71d4fc4fdae9ab76156e,PMC,Virus Pathogen Database and Analysis Resource (ViPR): A Comprehensive Bioinformatics Database and Analysis Resource for the Coronavirus Research Community,http://dx.doi.org/10.3390/v4113209,PMC3509690,23202522,CC BY,"Several viruses within the Coronaviridae family have been categorized as either emerging or re-emerging human pathogens, with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) being the most well known. The NIAID-sponsored Virus Pathogen Database and Analysis Resource (ViPR, www.viprbrc.org) supports bioinformatics workflows for a broad range of human virus pathogens and other related viruses, including the entire Coronaviridae family. ViPR provides access to sequence records, gene and protein annotations, immune epitopes, 3D structures, host factor data, and other data types through an intuitive web-based search interface. Records returned from these queries can then be subjected to web-based analyses including: multiple sequence alignment, phylogenetic inference, sequence variation determination, BLAST comparison, and metadata-driven comparative genomics statistical analysis. Additional tools exist to display multiple sequence alignments, view phylogenetic trees, visualize 3D protein structures, transfer existing reference genome annotations to new genomes, and store or share results from any search or analysis within personal private ‘Workbench’ spaces for future access. All of the data and integrated analysis and visualization tools in ViPR are made available without charge as a service to the Coronaviridae research community to facilitate the research and development of diagnostics, prophylactics, vaccines and therapeutics against these human pathogens.",2012 Nov 19,"['Pickett, Brett E.', 'Greer, Douglas S.', 'Zhang, Yun', 'Stewart, Lucy', 'Zhou, Liwei', 'Sun, Guangyu', 'Gu, Zhiping', 'Kumar, Sanjeev', 'Zaremba, Sam', 'Larsen, Christopher N.', 'Jen, Wei', 'Klem, Edward B.', 'Scheuermann, Richard H.']",Viruses,,,False
3e18531b5a0a745c732d05de8eac8862a9b6a8e9,PMC,Biogenesis and Dynamics of the Coronavirus Replicative Structures,http://dx.doi.org/10.3390/v4113245,PMC3509692,23202524,CC BY,"Coronaviruses are positive-strand RNA viruses that are important infectious agents of both animals and humans. A common feature among positive-strand RNA viruses is their assembly of replication-transcription complexes in association with cytoplasmic membranes. Upon infection, coronaviruses extensively rearrange cellular membranes into organelle-like replicative structures that consist of double-membrane vesicles and convoluted membranes to which the nonstructural proteins involved in RNA synthesis localize. Double-stranded RNA, presumably functioning as replicative intermediate during viral RNA synthesis, has been detected at the double-membrane vesicle interior. Recent studies have provided new insights into the assembly and functioning of the coronavirus replicative structures. This review will summarize the current knowledge on the biogenesis of the replicative structures, the membrane anchoring of the replication-transcription complexes, and the location of viral RNA synthesis, with particular focus on the dynamics of the coronavirus replicative structures and individual replication-associated proteins.",2012 Nov 21,"['Hagemeijer, Marne C.', 'Rottier, Peter J.M.', 'de Haan, Cornelis A.M.']",Viruses,,,True
30a8e34179b5cc12c971eaa2b40015a446f10621,PMC,Chitinase Dependent Control of Protozoan Cyst Burden in the Brain,http://dx.doi.org/10.1371/journal.ppat.1002990,PMC3510238,23209401,CC0,"Chronic infections represent a continuous battle between the host's immune system and pathogen replication. Many protozoan parasites have evolved a cyst lifecycle stage that provides it with increased protection from environmental degradation as well as endogenous host mechanisms of attack. In the case of Toxoplasma gondii, these cysts are predominantly found in the immune protected brain making clearance of the parasite more difficult and resulting in a lifelong infection. Currently, little is known about the nature of the immune response stimulated by the presence of these cysts or how they are able to propagate. Here we establish a novel chitinase-dependent mechanism of cyst control in the infected brain. Despite a dominant Th1 immune response during Toxoplasma infection there exists a population of alternatively activated macrophages (AAMØ) in the infected CNS. These cells are capable of cyst lysis via the production of AMCase as revealed by live imaging, and this chitinase is necessary for protective immunity within the CNS. These data demonstrate chitinase activity in the brain in response to a protozoan pathogen and provide a novel mechanism to facilitate cyst clearance during chronic infections.",2012 Nov 29,"['Nance, J. Philip', 'Vannella, Kevin M.', 'Worth, Danielle', 'David, Clément', 'Carter, David', 'Noor, Shahani', 'Hubeau, Cedric', 'Fitz, Lori', 'Lane, Thomas E.', 'Wynn, Thomas A.', 'Wilson, Emma H.']",PLoS Pathog,,,True
80ce020acc7d023a1bc60a5f42c2afc937e3a200,PMC,Diagnostic value of respiratory virus detection in symptomatic children using real-time PCR,http://dx.doi.org/10.1186/1743-422X-9-276,PMC3511061,23164039,CC BY,"BACKGROUND: Acute respiratory tract infections are an important public health problem. Sensitive and rapid diagnostic techniques have been developed and are used in daily clinical practice. Here we evaluate the clinical relevance of detecting 20 common respiratory pathogens by molecular methods in a general pediatric clinic. METHODS: Nasopharynx samples of children < 18 years of age with respiratory symptoms referred to a general pediatric clinic were tested for the presence of 19 viruses and Mycoplasma pneumoniae, using real-time polymerase chain reaction. RESULTS: Of 177 patients included in this retrospective study, 73% were positive for at least one virus. Respiratory syncytial virus (36.6%) and human rhinovirus (24%) were most frequently detected. Patients in whom a respiratory virus or Mycoplasma pneumoniae was detected, were younger (6 versus 24 months; p < 0.001) and more often hospitalized (116 versus 34; p = 0.001) than patients in whom no respiratory pathogen was detected. Also they were more likely to present with feeding problems, dyspnea, rhinorrhea and wheezing (all p < 0.05) than patients without a respiratory pathogen. In the majority of cases, clinicians did not change their antibiotic management after detecting a viral respiratory pathogen. No difference in mean Ct value was found between patients with one respiratory pathogen and those with >1 respiratory pathogen (30.5 versus 31.2; p = 0.573). CONCLUSION: Routine testing of common respiratory pathogens could lead to a better understanding of their role in disease in children with respiratory symptoms.",2012 Nov 19,"['Huijskens, Elisabeth G', 'Biesmans, Renée C', 'Buiting, Anton G', 'Obihara, Charles C', 'Rossen, John W']",Virol J,,,True
2a7c951e191425fd9fa5ac108f07a1f02eb75872,PMC,The changing phenotype of microglia from homeostasis to disease,http://dx.doi.org/10.1186/2047-9158-1-9,PMC3514090,23210447,CC BY,"It has been nearly a century since the early description of microglia by Rio-Hortega; since then many more biological and pathological features of microglia have been recognized. Today, microglia are generally considered to be beneficial to homeostasis at the resting state through their abilities to survey the environment and phagocytose debris. However, when activated microglia assume diverse phenotypes ranging from fully inflamed, which involves the release of many pro-inflammatory cytokines, to alternatively activated, releasing anti-inflammatory cytokines or neurotrophins, the consequences to neurons can range from detrimental to supportive. Due to the different experimental sets and conditions, contradictory results have been obtained regarding the controversial question of whether microglia are “good” or “bad.” While it is well understood that the dual roles of activated microglia depend on specific situations, the underlying mechanisms have remained largely unclear, and the interpretation of certain findings related to diverse microglial phenotypes continues to be problematic. In this review we discuss the functions of microglia in neuronal survival and neurogenesis, the crosstalk between microglia and surrounding cells, and the potential factors that could influence the eventual manifestation of microglia.",2012 Apr 24,"['Luo, Xiao-Guang', 'Chen, Sheng-Di']",Transl Neurodegener,,,True
854e623d1f875e4605b2ffd3f72599d063a56cc0,PMC,Diversity of Salmonella spp. serovars isolated from the intestines of water buffalo calves with gastroenteritis,http://dx.doi.org/10.1186/1746-6148-8-201,PMC3514206,23098237,CC BY,"BACKGROUND: Salmonellosis in water buffalo (Bubalus bubalis) calves is a widespread disease characterized by severe gastrointestinal lesions, profuse diarrhea and severe dehydration, occasionally exhibiting a systemic course. Several Salmonella serovars seem to be able to infect water buffalo, but Salmonella isolates collected from this animal species have been poorly characterized. In the present study, the prevalence of Salmonella spp. in water buffalo calves affected by lethal gastroenteritis was assessed, and a polyphasic characterization of isolated strains of S. Typhimurium was performed. RESULTS: The microbiological analysis of the intestinal contents obtained from 248 water buffalo calves affected by lethal gastroenteritis exhibited a significant prevalence of Salmonella spp. (25%), characterized by different serovars, most frequently Typhimurium (21%), Muenster (11%), and Give (11%). The 13 S. Typhimurium isolates were all associated with enterocolitis characterized by severe damage of the intestine, and only sporadically isolated with another possible causative agent responsible for gastroenteritis, such as Cryptosporidium spp., Rotavirus or Clostridium perfringens. Other Salmonella isolates were mostly isolated from minor intestinal lesions, and often (78% of cases) isolated with other microorganisms, mainly toxinogenic Escherichia coli (35%), Cryptosporidium spp. (20%) and Rotavirus (10%). The S. Typhimurium strains were characterized by phage typing and further genotyped by polymerase chain reaction (PCR) detection of 24 virulence genes. The isolates exhibited nine different phage types and 10 different genetic profiles. Three monophasic S. Typhimurium (B:4,12:i:-) isolates were also found and characterized, displaying three different phage types and three different virulotypes. The molecular characterization was extended to the 7 S. Muenster and 7 S. Give isolates collected, indicating the existence of different virulotypes also within these serovars. Three representative strains of S. Typhimurium were tested in vivo in a mouse model of mixed infection. The most pathogenic strain was characterized by a high number of virulence factors and the presence of the locus agfA, coding for a thin aggregative fimbria. CONCLUSIONS: These results provide evidence that Salmonella is frequently associated with gastroenteritis in water buffalo calves, particularly S. Typhimurium. Moreover, the variety in the number and distribution of different virulence markers among the collected S. Typhimurium strains suggests that within this serovar there are different pathotypes potentially responsible for different clinical syndromes.",2012 Oct 25,"['Borriello, Giorgia', 'Lucibelli, Maria G', 'Pesciaroli, Michele', 'Carullo, Maria R', 'Graziani, Caterina', 'Ammendola, Serena', 'Battistoni, Andrea', 'Ercolini, Danilo', 'Pasquali, Paolo', 'Galiero, Giorgio']",BMC Vet Res,,,True
3695704554777889f8232a9ea086df70bf17ff58,PMC,Severe Childhood Malaria Syndromes Defined by Plasma Proteome Profiles,http://dx.doi.org/10.1371/journal.pone.0049778,PMC3514223,23226502,CC BY,"BACKGROUND: Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood. Therefore it is important to understand the pathology underlying the development of CM and SMA, as opposed to uncomplicated malaria (UM). Different host responses to infection are likely to be reflected in plasma proteome-patterns that associate with clinical status and therefore provide indicators of the pathogenesis of these syndromes. METHODS AND FINDINGS: Plasma and comprehensive clinical data for discovery and validation cohorts were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, an urban and densely populated holoendemic malaria area in Nigeria. A total of 946 children participated in this study. Plasma was subjected to high-throughput proteomic profiling. Statistical pattern-recognition methods were used to find proteome-patterns that defined disease groups. Plasma proteome-patterns accurately distinguished children with CM and with SMA from those with UM, and from healthy or severely ill malaria-negative children. CONCLUSIONS: We report that an accurate definition of the major childhood malaria syndromes can be achieved using plasma proteome-patterns. Our proteomic data can be exploited to understand the pathogenesis of the different childhood severe malaria syndromes.",2012 Dec 4,"['Burté, Florence', 'Brown, Biobele J.', 'Orimadegun, Adebola E.', 'Ajetunmobi, Wasiu A.', 'Battaglia, Francesca', 'Ely, Barry K.', 'Afolabi, Nathaniel K.', 'Athanasakis, Dimitrios', 'Akinkunmi, Francis', 'Kowobari, Olayinka', 'Omokhodion, Samuel', 'Osinusi, Kikelomo', 'Akinbami, Felix O.', 'Shokunbi, Wuraola A.', 'Sodeinde, Olugbemiro', 'Fernandez-Reyes, Delmiro']",PLoS One,,,True
4f9d106c41459601d3804f9db29621c92c321921,PMC,Demographics and economic burden of un-owned cats and dogs in the UK: results of a 2010 census,http://dx.doi.org/10.1186/1746-6148-8-163,PMC3514250,22974242,CC BY,"BACKGROUND: The population of dogs and cats passing through rescue shelters may be subject to compromised welfare and increased susceptibility to disease. Little information exists to describe this population, its dynamics and associated management practices. The aim of this study was to carry out a census of un-owned cats and dogs in the UK in 2010, and to document the origins, destinations, husbandry and costs associated with the care of these animals. RESULTS: A sampling frame was constructed by searching the databases of publicly registered charities for England, Scotland and Wales, registers of breed rescues, and by internet searches of animal welfare websites. Overall, 2,352 contacts for 1,380 organisations were identified. All were sent a postal questionnaire asking for data on the number of dogs and cats housed, their origins and eventual outcomes, and details of husbandry between January 1(st) and December 31(st) 2010. For those which were registered charities (595), financial records were also obtained. A response rate of 38.8% was obtained. Overall, in 2010, 89,571 dogs and 156,826 cats entered the care of the participating organisations. Approximately half of these animals were relinquished by their owners. Other origins included being found as strays or confiscated for welfare purposes. Seventy-five per cent of dogs and 77.1% of cats were rehomed. The next most common outcome was euthanasia, accounting for 10.4% of dogs and 13.2% cats. For dogs and cats, 44.3% and 62% of participants respectively reported having a waiting list, which frequently exceeded the actual capacity of the facility. Over 19,000 people were involved in the care of these animals, on a paid or voluntary basis. Financial records were available for 519/595 (87.2%) of the registered charities, and their total expenditure in 2010 was £340 million. CONCLUSIONS: This study showed that a large number of animals become un-owned each year, which could have considerable implications for their welfare. Despite the resources expended, demand still exceeds capacity for many organisations, and a substantial number of both cats and dogs are euthanased, suggesting that further understanding of how and why these animals become un-owned is essential in order to target interventions.",2012 Sep 13,"['Stavisky, Jenny', 'Brennan, Marnie L', 'Downes, Martin', 'Dean, Rachel']",BMC Vet Res,,,True
3c8a38879c8d9910167b2dab37c2d98e17701141,PMC,Analysis of the swine tracheobronchial lymph node transcriptomic response to infection with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus,http://dx.doi.org/10.1186/1746-6148-8-208,PMC3514351,23110781,CC BY,"BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen of swine worldwide. Emergence in 2006 of a novel highly pathogenic PRRSV (HP-PRRSV) isolate in China necessitated a comparative investigation into the host transcriptome response in tracheobronchial lymph nodes (TBLN) 13 days post-infection with HP-PRRSV rJXwn06, PRRSV strain VR-2332 or sham inocula. RNA from each was prepared for next-generation sequencing. Amplified library constructs were directly sequenced and a list of sequence transcripts and counts was generated using an RNAseq analysis pipeline to determine differential gene expression. Transcripts were annotated and relative abundance was calculated based upon the number of times a given transcript was represented in the library. RESULTS: Major changes in transcript abundance occurred in response to infection with either PRRSV strain, each with over 630 differentially expressed transcripts. The largest increase in transcript level for either virus versus sham-inoculated controls were three serum amyloid A2 acute-phase isoforms. However, the degree of up or down-regulation of transcripts following infection with HP-PRRSV rJXwn06 was greater than transcript changes observed with US PRRSV VR-2332. Also, of 632 significantly altered transcripts within the HP-PRRSV rJXwn06 library 55 were up-regulated and 69 were down-regulated more than 3-fold, whilst in the US PRRSV VR-2332 library only 4 transcripts were up-regulated and 116 were down-regulated more than 3-fold. CONCLUSIONS: The magnitude of differentially expressed gene profiles detected in HP-PRRSV rJXwn06 infected pigs as compared to VR-2332 infected pigs was consistent with the increased pathogenicity of the HP-PRRSV in vivo.",2012 Oct 30,"['Miller, Laura C', 'Fleming, Damarius', 'Arbogast, Andrew', 'Bayles, Darrell O', 'Guo, Baoqing', 'Lager, Kelly M', 'Henningson, Jamie N', 'Schlink, Sarah N', 'Yang, Han-Chun', 'Faaberg, Kay S', 'Kehrli, Marcus E']",BMC Vet Res,,,True
c19b92f638a71bdf631c296aee8d9fbfd4202034,PMC,FGF-9 accelerates epithelial invagination for ectodermal organogenesis in real time bioengineered organ manipulation,http://dx.doi.org/10.1186/1478-811X-10-34,PMC3515343,23176204,CC BY,"BACKGROUND: Epithelial invagination is important for initiation of ectodermal organogenesis. Although many factors regulate ectodermal organogenesis, there is not any report about their functions in real-time study. Electric cell-substrate impedance sensing (ECIS), a non-invasive, real-time surveillance system, had been used to detect changes in organ cell layer thickness through quantitative monitoring of the impedance of a cell-to-microelectrode interface over time. It was shown to be a good method for identifying significant real-time changes of cells. The purpose of this study is to establish a combined bioengineered organ-ECIS model for investigating the real time effects of fibroblast growth factor-9 (FGF-9) on epithelial invagination in bioengineered ectodermal organs. We dissected epithelial and mesenchymal cells from stage E14.5 murine molar tooth germs and identified the real-time effects of FGF-9 on epithelial-mesenchymal interactions using this combined bioengineered organ-ECIS model. RESULTS: Measurement of bioengineered ectodermal organ thickness showed that Fibroblast growth factor-9 (FGF-9) accelerates epithelial invagination in reaggregated mesenchymal cell layer within 3 days. Gene expression analysis revealed that FGF-9 stimulates and sustains early Ameloblastin and Amelogenin expression during odontogenesis. CONCLUSIONS: This is the first real-time study to show that, FGF-9 plays an important role in epithelial invagination and initiates ectodermal organogenesis. Based on these findings, we suggest FGF-9 can be applied for further study in ectodermal organ regeneration, and we also proposed that the ‘FGF-BMP balancing system’ is important for manipulating the morphogenesis of ectodermal organs. The combined bioengineered organ-ECIS model is a promising method for ectodermal organ engineering and regeneration research.",2012 Nov 23,"['Tai, Yun-Yuan', 'Chen, Rung-Shu', 'Lin, Yi', 'Ling, Thai-Yen', 'Chen, Min-Huey']",Cell Commun Signal,,,True
5a054a570f409d5c2006369f19addc98d024b6c1,PMC,Predicting pseudoknotted structures across two RNA sequences,http://dx.doi.org/10.1093/bioinformatics/bts575,PMC3516145,23044552,CC BY,"Motivation: Laboratory RNA structure determination is demanding and costly and thus, computational structure prediction is an important task. Single sequence methods for RNA secondary structure prediction are limited by the accuracy of the underlying folding model, if a structure is supported by a family of evolutionarily related sequences, one can be more confident that the prediction is accurate. RNA pseudoknots are functional elements, which have highly conserved structures. However, few comparative structure prediction methods can handle pseudoknots due to the computational complexity. Results: A comparative pseudoknot prediction method called DotKnot-PW is introduced based on structural comparison of secondary structure elements and H-type pseudoknot candidates. DotKnot-PW outperforms other methods from the literature on a hand-curated test set of RNA structures with experimental support. Availability: DotKnot-PW and the RNA structure test set are available at the web site http://dotknot.csse.uwa.edu.au/pw. Contact: janaspe@csse.uwa.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.",2012 Dec 1,"['Sperschneider, Jana', 'Datta, Amitava', 'Wise, Michael J.']",Bioinformatics,,,True
98c7a28b30c1faf0ddd330afa35e4329e4725cd8,PMC,Predicting pseudoknotted structures across two RNA sequences,http://dx.doi.org/10.1093/bioinformatics/bts575,PMC3516145,23044552,CC BY,"Motivation: Laboratory RNA structure determination is demanding and costly and thus, computational structure prediction is an important task. Single sequence methods for RNA secondary structure prediction are limited by the accuracy of the underlying folding model, if a structure is supported by a family of evolutionarily related sequences, one can be more confident that the prediction is accurate. RNA pseudoknots are functional elements, which have highly conserved structures. However, few comparative structure prediction methods can handle pseudoknots due to the computational complexity. Results: A comparative pseudoknot prediction method called DotKnot-PW is introduced based on structural comparison of secondary structure elements and H-type pseudoknot candidates. DotKnot-PW outperforms other methods from the literature on a hand-curated test set of RNA structures with experimental support. Availability: DotKnot-PW and the RNA structure test set are available at the web site http://dotknot.csse.uwa.edu.au/pw. Contact: janaspe@csse.uwa.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.",2012 Dec 1,"['Sperschneider, Jana', 'Datta, Amitava', 'Wise, Michael J.']",Bioinformatics,,,False
73e3d6f3f33c747bffbbb8122ab855bfb59676db,PMC,Exhaled Air Dispersion during Coughing with and without Wearing a Surgical or N95 Mask,http://dx.doi.org/10.1371/journal.pone.0050845,PMC3516468,23239991,CC BY,"OBJECTIVES: We compared the expelled air dispersion distances during coughing from a human patient simulator (HPS) lying at 45° with and without wearing a surgical mask or N95 mask in a negative pressure isolation room. METHODS: Airflow was marked with intrapulmonary smoke. Coughing bouts were generated by short bursts of oxygen flow at 650, 320, and 220L/min to simulate normal, mild and poor coughing efforts, respectively. The coughing jet was revealed by laser light-sheet and images were captured by high definition video. Smoke concentration in the plume was estimated from the light scattered by smoke particles. Significant exposure was arbitrarily defined where there was ≥ 20% of normalized smoke concentration. RESULTS: During normal cough, expelled air dispersion distances were 68, 30 and 15 cm along the median sagittal plane when the HPS wore no mask, a surgical mask and a N95 mask, respectively. In moderate lung injury, the corresponding air dispersion distances for mild coughing efforts were reduced to 55, 27 and 14 cm, respectively, p < 0.001. The distances were reduced to 30, 24 and 12 cm, respectively during poor coughing effort as in severe lung injury. Lateral dispersion distances during normal cough were 0, 28 and 15 cm when the HPS wore no mask, a surgical mask and a N95 mask, respectively. CONCLUSIONS: Normal cough produced a turbulent jet about 0.7 m towards the end of the bed from the recumbent subject. N95 mask was more effective than surgical mask in preventing expelled air leakage during coughing but there was still significant sideway leakage.",2012 Dec 5,"['Hui, David S.', 'Chow, Benny K.', 'Chu, Leo', 'Ng, Susanna S.', 'Lee, Nelson', 'Gin, Tony', 'Chan, Matthew T. V.']",PLoS One,,,True
42c1d88111ece7fdf4a80dc8ddb30be44b211d80,PMC,Rhesus Macaque Theta Defensins Suppress Inflammatory Cytokines and Enhance Survival in Mouse Models of Bacteremic Sepsis,http://dx.doi.org/10.1371/journal.pone.0051337,PMC3516535,23236475,CC BY,"Theta-defensins (θ-defensins) are macrocyclic antimicrobial peptides expressed in leukocytes of Old World monkeys. The peptides are broad spectrum microbicides in vitro and numerous θ-defensin isoforms have been identified in granulocytes of rhesus macaques and Olive baboons. Several mammalian α- and β-defensins, genetically related to θ-defensins, have proinflammatory and immune-activating properties that bridge innate and acquired immunity. In the current study we analyzed the immunoregulatory properties of rhesus θ-defensins 1–5 (RTDs 1–5). RTD-1, the most abundant θ-defensin in macaques, reduced the levels of TNF, IL-1α, IL-1β, IL-6, and IL-8 secreted by blood leukocytes stimulated by several TLR agonists. RTDs 1–5 suppressed levels of soluble TNF released by bacteria- or LPS-stimulated blood leukocytes and THP-1 monocytes. Despite their highly conserved conformation and amino acid sequences, the anti-TNF activities of RTDs 1–5 varied by as much as 10-fold. Systemically administered RTD-1 was non-toxic for BALB/c mice, and escalating intravenous doses were well tolerated and non-immunogenic in adult chimpanzees. The peptide was highly stable in serum and plasma. Single dose administration of RTD-1 at 5 mg/kg significantly improved survival of BALB/c mice with E. coli peritonitis and cecal ligation-and-puncture induced polymicrobial sepsis. Peptide treatment reduced serum levels of several inflammatory cytokines/chemokines in bacteremic animals. Collectively, these results indicate that the anti-inflammatory properties of θ-defensins in vitro and in vivo are mediated by the suppression of numerous proinflammatory cytokines and blockade of TNF release may be a primary effect.",2012 Dec 6,"['Schaal, Justin B.', 'Tran, Dat', 'Tran, Patti', 'Ösapay, George', 'Trinh, Katie', 'Roberts, Kevin D.', 'Brasky, Kathleen M.', 'Tongaonkar, Prasad', 'Ouellette, André J.', 'Selsted, Michael E.']",PLoS One,,,True
8984416a285ced3a8855c5b4a473d02ab50e73d0,PMC,Three-Dimensional Architecture and Biogenesis of Membrane Structures Associated with Hepatitis C Virus Replication,http://dx.doi.org/10.1371/journal.ppat.1003056,PMC3516559,23236278,CC BY,"All positive strand RNA viruses are known to replicate their genomes in close association with intracellular membranes. In case of the hepatitis C virus (HCV), a member of the family Flaviviridae, infected cells contain accumulations of vesicles forming a membranous web (MW) that is thought to be the site of viral RNA replication. However, little is known about the biogenesis and three-dimensional structure of the MW. In this study we used a combination of immunofluorescence- and electron microscopy (EM)-based methods to analyze the membranous structures induced by HCV in infected cells. We found that the MW is derived primarily from the endoplasmic reticulum (ER) and contains markers of rough ER as well as markers of early and late endosomes, COP vesicles, mitochondria and lipid droplets (LDs). The main constituents of the MW are single and double membrane vesicles (DMVs). The latter predominate and the kinetic of their appearance correlates with kinetics of viral RNA replication. DMVs are induced primarily by NS5A whereas NS4B induces single membrane vesicles arguing that MW formation requires the concerted action of several HCV replicase proteins. Three-dimensional reconstructions identify DMVs as protrusions from the ER membrane into the cytosol, frequently connected to the ER membrane via a neck-like structure. In addition, late in infection multi-membrane vesicles become evident, presumably as a result of a stress-induced reaction. Thus, the morphology of the membranous rearrangements induced in HCV-infected cells resemble those of the unrelated picorna-, corona- and arteriviruses, but are clearly distinct from those of the closely related flaviviruses. These results reveal unexpected similarities between HCV and distantly related positive-strand RNA viruses presumably reflecting similarities in cellular pathways exploited by these viruses to establish their membranous replication factories.",2012 Dec 6,"['Romero-Brey, Inés', 'Merz, Andreas', 'Chiramel, Abhilash', 'Lee, Ji-Young', 'Chlanda, Petr', 'Haselman, Uta', 'Santarella-Mellwig, Rachel', 'Habermann, Anja', 'Hoppe, Simone', 'Kallis, Stephanie', 'Walther, Paul', 'Antony, Claude', 'Krijnse-Locker, Jacomine', 'Bartenschlager, Ralf']",PLoS Pathog,,,True
0b05d3ede3351f8b3edb22c74b0cfe933ba408c1,PMC,Cathepsin B & L Are Not Required for Ebola Virus Replication,http://dx.doi.org/10.1371/journal.pntd.0001923,PMC3516577,23236527,CC0,"Ebola virus (EBOV), family Filoviridae, emerged in 1976 on the African continent. Since then it caused several outbreaks of viral hemorrhagic fever in humans with case fatality rates up to 90% and remains a serious Public Health concern and biothreat pathogen. The most pathogenic and best-studied species is Zaire ebolavirus (ZEBOV). EBOV encodes one viral surface glycoprotein (GP), which is essential for replication, a determinant of pathogenicity and an important immunogen. GP mediates viral entry through interaction with cellular surface molecules, which results in the uptake of virus particles via macropinocytosis. Later in this pathway endosomal acidification activates the cysteine proteases Cathepsin B and L (CatB, CatL), which have been shown to cleave ZEBOV-GP leading to subsequent exposure of the putative receptor-binding and fusion domain and productive infection. We studied the effect of CatB and CatL on in vitro and in vivo replication of EBOV. Similar to previous findings, our results show an effect of CatB, but not CatL, on ZEBOV entry into cultured cells. Interestingly, cell entry by other EBOV species (Bundibugyo, Côte d'Ivoire, Reston and Sudan ebolavirus) was independent of CatB or CatL as was EBOV replication in general. To investigate whether CatB and CatL have a role in vivo during infection, we utilized the mouse model for ZEBOV. Wild-type (control), catB(−/−) and catL(−/−) mice were equally susceptible to lethal challenge with mouse-adapted ZEBOV with no difference in virus replication and time to death. In conclusion, our results show that CatB and CatL activity is not required for EBOV replication. Furthermore, EBOV glycoprotein cleavage seems to be mediated by an array of proteases making targeted therapeutic approaches difficult.",2012 Dec 6,"['Marzi, Andrea', 'Reinheckel, Thomas', 'Feldmann, Heinz']",PLoS Negl Trop Dis,,,True
aaf71afd1d3f2d1ee34ba2fb720aca20c35a303b,PMC,Digital Surveillance: A Novel Approach to Monitoring the Illegal Wildlife Trade,http://dx.doi.org/10.1371/journal.pone.0051156,PMC3517447,23236444,CC BY,"A dearth of information obscures the true scale of the global illegal trade in wildlife. Herein, we introduce an automated web crawling surveillance system developed to monitor reports on illegally traded wildlife. A resource for enforcement officials as well as the general public, the freely available website, http://www.healthmap.org/wildlifetrade, provides a customizable visualization of worldwide reports on interceptions of illegally traded wildlife and wildlife products. From August 1, 2010 to July 31, 2011, publicly available English language illegal wildlife trade reports from official and unofficial sources were collected and categorized by location and species involved. During this interval, 858 illegal wildlife trade reports were collected from 89 countries. Countries with the highest number of reports included India (n = 146, 15.6%), the United States (n = 143, 15.3%), South Africa (n = 75, 8.0%), China (n = 41, 4.4%), and Vietnam (n = 37, 4.0%). Species reported as traded or poached included elephants (n = 107, 12.5%), rhinoceros (n = 103, 12.0%), tigers (n = 68, 7.9%), leopards (n = 54, 6.3%), and pangolins (n = 45, 5.2%). The use of unofficial data sources, such as online news sites and social networks, to collect information on international wildlife trade augments traditional approaches drawing on official reporting and presents a novel source of intelligence with which to monitor and collect news in support of enforcement against this threat to wildlife conservation worldwide.",2012 Dec 7,"['Sonricker Hansen, Amy L.', 'Li, Annie', 'Joly, Damien', 'Mekaru, Sumiko', 'Brownstein, John S.']",PLoS One,,,True
64c22236bc20680680fffab70eedef1f21641bd0,PMC,Intranasal Administration of dsRNA Analog Poly(I:C) Induces Interferon-α Receptor-Dependent Accumulation of Antigen Experienced T Cells in the Airways,http://dx.doi.org/10.1371/journal.pone.0051351,PMC3517467,23236482,CC BY,"Polyriboinosinic-polyribocytoidylic acid (pIC), a synthetic dsRNA, acts as an adjuvant that boosts immune responses and protection. Intranasal (IN) administration of pIC has recently been used to adjuvant influenza virus vaccines; however, the effects of IN pIC administration on pulmonary T cell responses remain unclear. Here we show that a single IN administered dose of dsRNA into mice induced local Th1 chemokine production in the lungs and airways, and generated a biphasic and sustained migration of T lymphocytes to the airways. Furthermore, IN pIC-induced chemokine production and T cell recruitment to the airways were interferon-α receptor (IFNAR) signaling dependent. The effect of dsRNA on T cell recruitment to the airways was also dependent on the presence of high molecular weight (HMW) pIC, as a low molecular weight (LMW) pIC preparation known to only interact with TLR3 did not elicit the same effect on T cell migration to the airways, suggesting that the observed effects were dependent upon dsRNA recognition by multiple pattern recognition receptors (PPRs). IN pIC was additionally capable of stimulating low levels of T cell proliferation in the draining lymph nodes approximately 4–6 days after treatment that preceded a small population of de-novo T cells found in the airways by day 10. Taken together, these results demonstrate that the adjuvant effect of IN pIC that results in enhanced T cell proliferation and sustained T cell recruitment to the airways requires multiple PRRs and IFNAR signaling.",2012 Dec 7,"['McNally, Beth', 'Willette, Meredith', 'Ye, Fang', 'Partida-Sanchez, Santiago', 'Flaño, Emilio']",PLoS One,,,True
380e9f8318abdddde5c3c6b30802f48f4d3540c4,PMC,National inventory of emergency departments in Singapore,http://dx.doi.org/10.1186/1865-1380-5-38,PMC3518169,23114079,CC BY,"BACKGROUND: Emergency departments (EDs) are the basic units of emergency care. We performed a national inventory of all Singapore EDs and describe their characteristics and capabilities. METHODS: Singapore EDs accessible to the general public 24/7 were surveyed using the National ED Inventories instrument ( http://www.emnet-nedi.org). ED staff members were asked about ED characteristics with reference to calendar year 2007. RESULTS: Fourteen EDs participated (100% response). All EDs were located in hospitals, and most (92%) were independent departments. One was a psychiatric ED; the rest were general EDs. Among general EDs, all had a contiguous layout, with medical and surgical care provided in one area. All but two EDs saw both adults and children; one ED was adult-only, and the other saw only children. Six were in the public sector and seven in private health-care institutions, with public EDs seeing the majority (78%) of ED patients. Each private ED had an annual patient census of <30,000. These EDs received 2% of ambulances and had an inpatient admission rate of 7%. Each public ED had an annual census of >60,000. They received 98% of ambulances and had an inpatient admission rate of 30%. Two public EDs reported being overcapacity; no private EDs did. For both public and private EDs, availability of consultant resources in EDs was high, while technological resources varied. CONCLUSION: Characteristics and capabilities of Singapore EDs varied and were largely dependent on whether they are in public or private hospitals. This initial inventory establishes a benchmark to further monitor the development of emergency care in Singapore.",2012 Oct 31,"['Wen, Leana S', 'Venkataraman, Anantharaman', 'Sullivan, Ashley F', 'Camargo, Carlos A']",Int J Emerg Med,,,True
0e3da58a0d46d88ee542720cc9e1f594a3d69a79,PMC,The influence of climatic conditions on the transmission dynamics of the 2009 A/H1N1 influenza pandemic in Chile,http://dx.doi.org/10.1186/1471-2334-12-298,PMC3518181,23148597,CC BY,"BACKGROUND: The role of demographic factors, climatic conditions, school cycles, and connectivity patterns in shaping the spatio-temporal dynamics of pandemic influenza is not clearly understood. Here we analyzed the spatial, age and temporal evolution of the 2009 A/H1N1 influenza pandemic in Chile, a southern hemisphere country covering a long and narrow strip comprising latitudes 17°S to 56°S. METHODS: We analyzed the dissemination patterns of the 2009 A/H1N1 pandemic across 15 regions of Chile based on daily hospitalizations for severe acute respiratory disease and laboratory confirmed A/H1N1 influenza infection from 01-May to 31-December, 2009. We explored the association between timing of pandemic onset and peak pandemic activity and several geographical and demographic indicators, school vacations, climatic factors, and international passengers. We also estimated the reproduction number (R) based on the growth rate of the exponential pandemic phase by date of symptoms onset, estimated using maximum likelihood methods. RESULTS: While earlier pandemic onset was associated with larger population size, there was no association with connectivity, demographic, school or climatic factors. In contrast, there was a latitudinal gradient in peak pandemic timing, representing a 16-39-day lag in disease activity from the southern regions relative to the northernmost region (P < 0.001). Geographical differences in latitude of Chilean regions, maximum temperature and specific humidity explained 68.5% of the variability in peak timing (P = 0.01). In addition, there was a decreasing gradient in reproduction number from south to north Chile (P < 0.0001). The regional mean R estimates were 1.6-2.0, 1.3-1.5, and 1.2-1.3 for southern, central and northern regions, respectively, which were not affected by the winter vacation period. CONCLUSIONS: There was a lag in the period of most intense 2009 pandemic influenza activity following a South to North traveling pattern across regions of Chile, significantly associated with geographical differences in minimum temperature and specific humidity. The latitudinal gradient in timing of pandemic activity was accompanied by a gradient in reproduction number (P < 0.0001). Intensified surveillance strategies in colder and drier southern regions could lead to earlier detection of pandemic influenza viruses and improved control outcomes.",2012 Nov 13,"['Chowell, Gerardo', 'Towers, Sherry', 'Viboud, Cécile', 'Fuentes, Rodrigo', 'Sotomayor, Viviana', 'Simonsen, Lone', 'Miller, Mark A', 'Lima, Mauricio', 'Villarroel, Claudia', 'Chiu, Monica', 'Villarroel, Jose E', 'Olea, Andrea']",BMC Infect Dis,,,True
4dfa5a3533ef3b79abb871f4b4132f8b654a52eb,PMC,The influence of climatic conditions on the transmission dynamics of the 2009 A/H1N1 influenza pandemic in Chile,http://dx.doi.org/10.1186/1471-2334-12-298,PMC3518181,23148597,CC BY,"BACKGROUND: The role of demographic factors, climatic conditions, school cycles, and connectivity patterns in shaping the spatio-temporal dynamics of pandemic influenza is not clearly understood. Here we analyzed the spatial, age and temporal evolution of the 2009 A/H1N1 influenza pandemic in Chile, a southern hemisphere country covering a long and narrow strip comprising latitudes 17°S to 56°S. METHODS: We analyzed the dissemination patterns of the 2009 A/H1N1 pandemic across 15 regions of Chile based on daily hospitalizations for severe acute respiratory disease and laboratory confirmed A/H1N1 influenza infection from 01-May to 31-December, 2009. We explored the association between timing of pandemic onset and peak pandemic activity and several geographical and demographic indicators, school vacations, climatic factors, and international passengers. We also estimated the reproduction number (R) based on the growth rate of the exponential pandemic phase by date of symptoms onset, estimated using maximum likelihood methods. RESULTS: While earlier pandemic onset was associated with larger population size, there was no association with connectivity, demographic, school or climatic factors. In contrast, there was a latitudinal gradient in peak pandemic timing, representing a 16-39-day lag in disease activity from the southern regions relative to the northernmost region (P < 0.001). Geographical differences in latitude of Chilean regions, maximum temperature and specific humidity explained 68.5% of the variability in peak timing (P = 0.01). In addition, there was a decreasing gradient in reproduction number from south to north Chile (P < 0.0001). The regional mean R estimates were 1.6-2.0, 1.3-1.5, and 1.2-1.3 for southern, central and northern regions, respectively, which were not affected by the winter vacation period. CONCLUSIONS: There was a lag in the period of most intense 2009 pandemic influenza activity following a South to North traveling pattern across regions of Chile, significantly associated with geographical differences in minimum temperature and specific humidity. The latitudinal gradient in timing of pandemic activity was accompanied by a gradient in reproduction number (P < 0.0001). Intensified surveillance strategies in colder and drier southern regions could lead to earlier detection of pandemic influenza viruses and improved control outcomes.",2012 Nov 13,"['Chowell, Gerardo', 'Towers, Sherry', 'Viboud, Cécile', 'Fuentes, Rodrigo', 'Sotomayor, Viviana', 'Simonsen, Lone', 'Miller, Mark A', 'Lima, Mauricio', 'Villarroel, Claudia', 'Chiu, Monica', 'Villarroel, Jose E', 'Olea, Andrea']",BMC Infect Dis,,,True
ea7ae35a6203f68c29d8aa305a9d89ba8c76d284,PMC,Diagnostic issues and capabilities in 48 isolation facilities in 16 European countries: data from EuroNHID surveys,http://dx.doi.org/10.1186/1756-0500-5-527,PMC3519610,23009598,CC BY,"BACKGROUND: Highly infectious diseases (HIDs) are defined as being transmissible from person to person, causing life-threatening illnesses and presenting a serious public health hazard. The sampling, handling and transport of specimens from patients with HIDs present specific bio-safety concerns. FINDINGS: The European Network for HID project aimed to record, in a cross-sectional study, the infection control capabilities of referral centers for HIDs across Europe and assesses the level of achievement to previously published guidelines. In this paper, we report the current diagnostic capabilities and bio-safety measures applied to diagnostic procedures in these referral centers. Overall, 48 isolation facilities in 16 European countries were evaluated. Although 81% of these referral centers are located near a biosafety level 3 laboratory, 11% and 31% of them still performed their microbiological and routine diagnostic analyses, respectively, without bio-safety measures. CONCLUSIONS: The discrepancies among the referral centers surveyed between the level of practices and the European Network of Infectious Diseases (EUNID) recommendations have multiple reasons of which the interest of the individuals in charge and the investment they put in preparedness to emerging outbreaks. Despite the fact that the less prepared centers can improve by just updating their practice and policies any support to help them to achieve an acceptable level of biosecurity is welcome.",2012 Sep 25,"['Thiberville, Simon-Djamel', 'Schilling, Stefan', 'De Iaco, Giuseppina', 'Fusco, Francesco Maria', 'Thomson, Gail', 'Maltezou, Helen C', 'Gottschalk, Rene', 'Brodt, Reinhard H', 'Bannister, Barbara', 'Puro, Vincenzo', 'Ippolito, Giuseppe', 'Brouqui, Philippe']",BMC Res Notes,,,True
7f911fcc63f431561d8dc09ed831ce558ca2d773,PMC,Identification of a conserved linear B-cell epitope in the M protein of porcine epidemic diarrhea virus,http://dx.doi.org/10.1186/1743-422X-9-225,PMC3519612,23025700,CC BY,"BACKGROUND: The major structural protein of coronaviruses, the membrane (M) protein, can elicit the formation of protective antibodies, but little information is available about the M protein of porcine epidemic diarrhea virus (PEDV). Identification of epitopes on the PEDV M protein will be helpful in the elucidation of the antigenic properties of this protein. RESULTS: One hybridoma cell line secreting anti-M protein monoclonal antibody (McAb) was generated and designated 4D4. To map the epitopes on the PEDV M protein, a total of 17 partially overlapping fragments covering the C-terminus of M protein were expressed as fusion proteins with a 6×His tag or a GST tag. A linear motif, (193)TGWAFYVR(200), was identified by enzyme-linked immunosorbent assay (ELISA) and western blot (WB) analysis using McAb 4D4. The motif (195)WAFYVR(200) was the minimal requirement for reactivity, as demonstrated by removing amino acids individually from both ends of the motif (193)TGWAFYVR(200). The result of WB analysis showed that the 4D4-defined epitope could be recognized by PEDV-positive serum, but not transmissible gastroenteritis virus (TGEV)-positive serum. Furthermore, this epitope was highly conserved among different PEDV strains, as shown by alignment and comparison of sequences. CONCLUSION: A McAb, 4D4, directed against the M protein of PEDV, was obtained, and the 4D4-defined minimal epitope sequence was (195)WAFYVR(200). The McAb could serve as a candidate for development of a McAb-based antigen capture ELISA for detection of PEDV. The epitope identified provides a basis for the development of epitope-based differential diagnostic techniques and may be useful in the design of epitope-based vaccines.",2012 Oct 1,"['Zhang, Zhibang', 'Chen, Jianfei', 'Shi, Hongyan', 'Chen, Xiaojin', 'Shi, Da', 'Feng, Li', 'Yang, Bin']",Virol J,,,True
b5421a028a9ff8b2f36ad9be3c51d3d0cb78ddd6,PMC,"Nullbasic, a Potent Anti-HIV Tat Mutant, Induces CRM1-Dependent Disruption of HIV Rev Trafficking",http://dx.doi.org/10.1371/journal.pone.0051466,PMC3519632,23251541,CC BY,"Nullbasic, a mutant of the HIV-1 Tat protein, has anti-HIV-1 activity through mechanisms that include inhibition of Rev function and redistribution of the HIV-1 Rev protein from the nucleolus to the nucleoplasm and cytoplasm. Here we investigate the mechanism of this effect for the first time, establishing that redistribution of Rev by Nullbasic is not due to direct interaction between the two proteins. Rather, Nullbasic affects subcellular localization of cellular proteins that regulate Rev trafficking. In particular, Nullbasic induced redistribution of exportin 1 (CRM1), nucleophosmin (B23) and nucleolin (C23) from the nucleolus to the nucleus when Rev was coexpressed, but never in its absence. Inhibition of the Rev:CRM1 interaction by leptomycin B or a non-interacting RevM10 mutant completely blocked redistribution of Rev by Nullbasic. Finally, Nullbasic did not inhibit importin β- or transportin 1-mediated nuclear import, suggesting that cytoplasmic accumulation of Rev was due to increased export by CRM1. Overall, our data support the conclusion that CRM1-dependent subcellular redistribution of Rev from the nucleolus by Nullbasic is not through general perturbation of either nuclear import or export. Rather, Nullbasic appears to interact with and disrupt specific components of a Rev trafficking complex required for its nucleocytoplasmic shuttling and, in particular, its nucleolar accumulation.",2012 Dec 10,"['Lin, Min-Hsuan', 'Sivakumaran, Haran', 'Apolloni, Ann', 'Wei, Ting', 'Jans, David A.', 'Harrich, David']",PLoS One,,,True
2ab6b5e2628c1979ae2e65f9a0f9870cb3773d61,PMC,"Comparison of three multiplex PCR assays for the detection of respiratory viral infections: evaluation of xTAG respiratory virus panel fast assay, RespiFinder 19 assay and RespiFinder SMART 22 assay",http://dx.doi.org/10.1186/1471-2334-12-163,PMC3519643,22828244,CC BY,"BACKGROUND: A broad spectrum of pathogens is causative for respiratory tract infections, but symptoms are mostly similar. Therefore, the identification of the causative viruses and bacteria is only feasible using multiplex PCR or several monoplex PCR tests in parallel. METHODS: The analytical sensitivity of three multiplex PCR assays, RespiFinder-19, RespiFinder-SMART-22 and xTAG-Respiratory-Virus-Panel-Fast-Assay (RVP), were compared to monoplex real-time PCR with quantified standardized control material. All assays include the most common respiratory pathogens. RESULTS: To compare the analytical sensitivity of the multiplex assays, samples were inoculated with 13 different quantified viruses in the range of 10(1) to 10(5) copies/ml. Concordant results were received for rhinovirus, whereas the RVP detected influenzavirus, RSV and hMPV more frequently in low concentrations. The RespiFinder-19 and the RespiFinder-SMART-22 showed a higher analytical sensitivity for adenoviruses and coronaviruses, whereas the RVP was incapable to detect adenovirus and coronavirus in concentrations of 10(4) copies/ml. The RespiFinder-19 and RespiFinder-SMART-22A did not detect influenzaviruses (10(4) copies/ml) and RSV (10(3) copies/ml). The detection of all 13 viruses in one sample was only achieved using monoplex PCR. To analyze possible competitive amplification reactions between the different viruses, samples were further inoculated with only 4 different viruses in one sample. Compared to the detection of 13 viruses in parallel, only a few differences were found. The incidence of respiratory viruses was compared in tracheal secretion (TS) samples (n = 100) of mechanically ventilated patients in winter (n = 50) and summer (n = 50). In winter, respiratory viruses were detected in 32 TS samples (64%) by RespiFinder-19, whereas the detection rate with RVP was only 22%. The most frequent viruses were adenovirus (32%) and PIV-2 (20%). Multiple infections were detected in 16 TS samples (32%) by RespiFinder-19. Fewer infections were found in summer (RespiFinder-19: 20%; RVP: 6%). All positive results were verified using monoplex PCR. CONCLUSIONS: Multiplex PCR tests have a broad spectrum of pathogens to test at a time. Analysis of multiple inoculated samples revealed a different focus of the detected virus types by the three assays. Analysis of clinical samples showed a high concordance of detected viruses by the RespiFinder-19 compared to monoplex tests.",2012 Jul 24,"['Dabisch-Ruthe, Mareike', 'Vollmer, Tanja', 'Adams, Ortwin', 'Knabbe, Cornelius', 'Dreier, Jens']",BMC Infect Dis,,,True
a88ec297fe59d6c950ea8123ddda210a7b134032,PMC,A MultiSite Gateway(TM )vector set for the functional analysis of genes in the model Saccharomyces cerevisiae,http://dx.doi.org/10.1186/1471-2199-13-30,PMC3519679,22994806,CC BY,"BACKGROUND: Recombinatorial cloning using the Gateway(TM) technology has been the method of choice for high-throughput omics projects, resulting in the availability of entire ORFeomes in Gateway(TM) compatible vectors. The MultiSite Gateway(TM) system allows combining multiple genetic fragments such as promoter, ORF and epitope tag in one single reaction. To date, this technology has not been accessible in the yeast Saccharomyces cerevisiae, one of the most widely used experimental systems in molecular biology, due to the lack of appropriate destination vectors. RESULTS: Here, we present a set of three-fragment MultiSite Gateway(TM) destination vectors that have been developed for gene expression in S. cerevisiae and that allow the assembly of any promoter, open reading frame, epitope tag arrangement in combination with any of four auxotrophic markers and three distinct replication mechanisms. As an example of its applicability, we used yeast three-hybrid to provide evidence for the assembly of a ternary complex of plant proteins involved in jasmonate signalling and consisting of the JAZ, NINJA and TOPLESS proteins. CONCLUSION: Our vectors make MultiSite Gateway(TM) cloning accessible in S. cerevisiae and implement a fast and versatile cloning method for the high-throughput functional analysis of (heterologous) proteins in one of the most widely used model organisms for molecular biology research.",2012 Sep 20,"['Nagels Durand, Astrid', 'Moses, Tessa', 'De Clercq, Rebecca', 'Goossens, Alain', 'Pauwels, Laurens']",BMC Mol Biol,,,True
417fd2b2eba2473029f35d664f1bc72e03022eb1,PMC,Respiratory viruses from hospitalized children with severe pneumonia in the Philippines,http://dx.doi.org/10.1186/1471-2334-12-267,PMC3519714,23092190,CC BY,"BACKGROUND: Pneumonia remains a leading cause of child death in developing countries. The viruses in severe pneumonia remain poorly defined. METHODS: The study was conducted at the Eastern Visayas Regional Medical Center in Tacloban City, Philippines from May 2008 to May 2009. Patients aged 8 days to 13 years old who were admitted to the Department of Pediatrics with severe pneumonia were enrolled for the study. Upon admission, polymerase chain reaction was performed using nasopharyngeal swabs and blood cultures to detect respiratory viruses and bacteria, respectively. RESULT: Among the 819 patients enrolled, at least one virus was detected in 501 cases (61.2%). In addition, 423 cases were positive for a single virus while bacteria were detected in the blood culture sample of 31 cases. The most commonly detected viruses were human rhinoviruses (n = 189), including types A (n = 103), B (n = 17), and C (n = 69), and respiratory syncytial virus (RSV) (n = 165). Novel viruses such as human metapneumovirus, human coronavirus NL63, human bocavirus, and human polyomaviruses WU and KI were also detected. There were 70 deaths, and one or more viruses were detected in 35 (50%) of these cases. Positivity only for influenza A virus (OR = 4.3, 95% CI = 1.3-14.6) was significantly associated with fatal outcome. From the blood culture, Burkholderia cepacia group (n = 9), Streptococcus pneumoniae (n = 4), Staphylococcus aureus (n = 4), Haemophilus influenzae (n = 1), and Salmonella C1 (n = 1) were also isolated. CONCLUSION: Viruses were commonly detected in children with severe pneumonia in the Philippines. Hence, viral etiologies should be considered while developing better effective strategies to reduce child pneumonia-related deaths in developing countries.",2012 Oct 23,"['Suzuki, Akira', 'Lupisan, Socorro', 'Furuse, Yuki', 'Fuji, Naoko', 'Saito, Mariko', 'Tamaki, Raita', 'Galang, Hazel', 'Sombrero, Lydia', 'Mondoy, Melisa', 'Aniceto, Rapunzel', 'Olveda, Remigio', 'Oshitani, Hitoshi']",BMC Infect Dis,,,True
3ade01fb8514f2846a69bcfe3d6eb552b4cd24d0,PMC,Respiratory viruses from hospitalized children with severe pneumonia in the Philippines,http://dx.doi.org/10.1186/1471-2334-12-267,PMC3519714,23092190,CC BY,"BACKGROUND: Pneumonia remains a leading cause of child death in developing countries. The viruses in severe pneumonia remain poorly defined. METHODS: The study was conducted at the Eastern Visayas Regional Medical Center in Tacloban City, Philippines from May 2008 to May 2009. Patients aged 8 days to 13 years old who were admitted to the Department of Pediatrics with severe pneumonia were enrolled for the study. Upon admission, polymerase chain reaction was performed using nasopharyngeal swabs and blood cultures to detect respiratory viruses and bacteria, respectively. RESULT: Among the 819 patients enrolled, at least one virus was detected in 501 cases (61.2%). In addition, 423 cases were positive for a single virus while bacteria were detected in the blood culture sample of 31 cases. The most commonly detected viruses were human rhinoviruses (n = 189), including types A (n = 103), B (n = 17), and C (n = 69), and respiratory syncytial virus (RSV) (n = 165). Novel viruses such as human metapneumovirus, human coronavirus NL63, human bocavirus, and human polyomaviruses WU and KI were also detected. There were 70 deaths, and one or more viruses were detected in 35 (50%) of these cases. Positivity only for influenza A virus (OR = 4.3, 95% CI = 1.3-14.6) was significantly associated with fatal outcome. From the blood culture, Burkholderia cepacia group (n = 9), Streptococcus pneumoniae (n = 4), Staphylococcus aureus (n = 4), Haemophilus influenzae (n = 1), and Salmonella C1 (n = 1) were also isolated. CONCLUSION: Viruses were commonly detected in children with severe pneumonia in the Philippines. Hence, viral etiologies should be considered while developing better effective strategies to reduce child pneumonia-related deaths in developing countries.",2012 Oct 23,"['Suzuki, Akira', 'Lupisan, Socorro', 'Furuse, Yuki', 'Fuji, Naoko', 'Saito, Mariko', 'Tamaki, Raita', 'Galang, Hazel', 'Sombrero, Lydia', 'Mondoy, Melisa', 'Aniceto, Rapunzel', 'Olveda, Remigio', 'Oshitani, Hitoshi']",BMC Infect Dis,,,False
414a9d49055b96830b86bd3b4cb7b9e6973d05f6,PMC,Respiratory viruses from hospitalized children with severe pneumonia in the Philippines,http://dx.doi.org/10.1186/1471-2334-12-267,PMC3519714,23092190,CC BY,"BACKGROUND: Pneumonia remains a leading cause of child death in developing countries. The viruses in severe pneumonia remain poorly defined. METHODS: The study was conducted at the Eastern Visayas Regional Medical Center in Tacloban City, Philippines from May 2008 to May 2009. Patients aged 8 days to 13 years old who were admitted to the Department of Pediatrics with severe pneumonia were enrolled for the study. Upon admission, polymerase chain reaction was performed using nasopharyngeal swabs and blood cultures to detect respiratory viruses and bacteria, respectively. RESULT: Among the 819 patients enrolled, at least one virus was detected in 501 cases (61.2%). In addition, 423 cases were positive for a single virus while bacteria were detected in the blood culture sample of 31 cases. The most commonly detected viruses were human rhinoviruses (n = 189), including types A (n = 103), B (n = 17), and C (n = 69), and respiratory syncytial virus (RSV) (n = 165). Novel viruses such as human metapneumovirus, human coronavirus NL63, human bocavirus, and human polyomaviruses WU and KI were also detected. There were 70 deaths, and one or more viruses were detected in 35 (50%) of these cases. Positivity only for influenza A virus (OR = 4.3, 95% CI = 1.3-14.6) was significantly associated with fatal outcome. From the blood culture, Burkholderia cepacia group (n = 9), Streptococcus pneumoniae (n = 4), Staphylococcus aureus (n = 4), Haemophilus influenzae (n = 1), and Salmonella C1 (n = 1) were also isolated. CONCLUSION: Viruses were commonly detected in children with severe pneumonia in the Philippines. Hence, viral etiologies should be considered while developing better effective strategies to reduce child pneumonia-related deaths in developing countries.",2012 Oct 23,"['Suzuki, Akira', 'Lupisan, Socorro', 'Furuse, Yuki', 'Fuji, Naoko', 'Saito, Mariko', 'Tamaki, Raita', 'Galang, Hazel', 'Sombrero, Lydia', 'Mondoy, Melisa', 'Aniceto, Rapunzel', 'Olveda, Remigio', 'Oshitani, Hitoshi']",BMC Infect Dis,,,False
151812be7cb8160939baf6896a5c4f6fdfbfd973,PMC,Respiratory viruses from hospitalized children with severe pneumonia in the Philippines,http://dx.doi.org/10.1186/1471-2334-12-267,PMC3519714,23092190,CC BY,"BACKGROUND: Pneumonia remains a leading cause of child death in developing countries. The viruses in severe pneumonia remain poorly defined. METHODS: The study was conducted at the Eastern Visayas Regional Medical Center in Tacloban City, Philippines from May 2008 to May 2009. Patients aged 8 days to 13 years old who were admitted to the Department of Pediatrics with severe pneumonia were enrolled for the study. Upon admission, polymerase chain reaction was performed using nasopharyngeal swabs and blood cultures to detect respiratory viruses and bacteria, respectively. RESULT: Among the 819 patients enrolled, at least one virus was detected in 501 cases (61.2%). In addition, 423 cases were positive for a single virus while bacteria were detected in the blood culture sample of 31 cases. The most commonly detected viruses were human rhinoviruses (n = 189), including types A (n = 103), B (n = 17), and C (n = 69), and respiratory syncytial virus (RSV) (n = 165). Novel viruses such as human metapneumovirus, human coronavirus NL63, human bocavirus, and human polyomaviruses WU and KI were also detected. There were 70 deaths, and one or more viruses were detected in 35 (50%) of these cases. Positivity only for influenza A virus (OR = 4.3, 95% CI = 1.3-14.6) was significantly associated with fatal outcome. From the blood culture, Burkholderia cepacia group (n = 9), Streptococcus pneumoniae (n = 4), Staphylococcus aureus (n = 4), Haemophilus influenzae (n = 1), and Salmonella C1 (n = 1) were also isolated. CONCLUSION: Viruses were commonly detected in children with severe pneumonia in the Philippines. Hence, viral etiologies should be considered while developing better effective strategies to reduce child pneumonia-related deaths in developing countries.",2012 Oct 23,"['Suzuki, Akira', 'Lupisan, Socorro', 'Furuse, Yuki', 'Fuji, Naoko', 'Saito, Mariko', 'Tamaki, Raita', 'Galang, Hazel', 'Sombrero, Lydia', 'Mondoy, Melisa', 'Aniceto, Rapunzel', 'Olveda, Remigio', 'Oshitani, Hitoshi']",BMC Infect Dis,,,False
cb43de0358c05aba59dfb4957432fc2cbe31b30e,PMC,Antagonistic Pleiotropy and Fitness Trade-Offs Reveal Specialist and Generalist Traits in Strains of Canine Distemper Virus,http://dx.doi.org/10.1371/journal.pone.0050955,PMC3519774,23239996,CC BY,"Theoretically, homogeneous environments favor the evolution of specialists whereas heterogeneous environments favor generalists. Canine distemper is a multi-host carnivore disease caused by canine distemper virus (CDV). The described cell receptor of CDV is SLAM (CD150). Attachment of CDV hemagglutinin protein (CDV-H) to this receptor facilitates fusion and virus entry in cooperation with the fusion protein (CDV-F). We investigated whether CDV strains co-evolved in the large, homogeneous domestic dog population exhibited specialist traits, and strains adapted to the heterogeneous environment of smaller populations of different carnivores exhibited generalist traits. Comparison of amino acid sequences of the SLAM binding region revealed higher similarity between sequences from Canidae species than to sequences from other carnivore families. Using an in vitro assay, we quantified syncytia formation mediated by CDV-H proteins from dog and non-dog CDV strains in cells expressing dog, lion or cat SLAM. CDV-H proteins from dog strains produced significantly higher values with cells expressing dog SLAM than with cells expressing lion or cat SLAM. CDV-H proteins from strains of non-dog species produced similar values in all three cell types, but lower values in cells expressing dog SLAM than the values obtained for CDV-H proteins from dog strains. By experimentally changing one amino acid (Y549H) in the CDV-H protein of one dog strain we decreased expression of specialist traits and increased expression of generalist traits, thereby confirming its functional importance. A virus titer assay demonstrated that dog strains produced higher titers in cells expressing dog SLAM than cells expressing SLAM of non-dog hosts, which suggested possible fitness benefits of specialization post-cell entry. We provide in vitro evidence for the expression of specialist and generalist traits by CDV strains, and fitness trade-offs across carnivore host environments caused by antagonistic pleiotropy. These findings extend knowledge on CDV molecular epidemiology of particular relevance to wild carnivores.",2012 Dec 11,"['Nikolin, Veljko M.', 'Osterrieder, Klaus', 'von Messling, Veronika', 'Hofer, Heribert', 'Anderson, Danielle', 'Dubovi, Edward', 'Brunner, Edgar', 'East, Marion L.']",PLoS One,,,True
72613cfcf7d9ce3ba6d87fa24e2c220a15914d73,PMC,Quantification of the Host Response Proteome after Mammalian Reovirus T1L Infection,http://dx.doi.org/10.1371/journal.pone.0051939,PMC3519901,23240068,CC BY,"All viruses are dependent upon host cells for replication. Infection can induce profound changes within cells, including apoptosis, morphological changes, and activation of signaling pathways. Many of these alterations have been analyzed by gene arrays to measure the cellular “transcriptome.” We used SILAC (stable isotope labeling by amino acids in cell culture), combined with high-throughput 2-D HPLC/mass spectrometry, to determine relative quantitative differences in host proteins at 6 and 24 hours after infecting HEK293 cells with reovirus serotype 1 Lang (T1L). 3,076 host proteins were detected at 6hpi, of which 132 and 68 proteins were significantly up or down regulated, respectively. 2,992 cellular proteins, of which 104 and 49 were up or down regulated, respectively, were identified at 24hpi. IPA and DAVID analyses indicated proteins involved in cell death, cell growth factors, oxygen transport, cell structure organization and inflammatory defense response to virus were up-regulated, whereas proteins involved in apoptosis, isomerase activity, and metabolism were down-regulated. These proteins and pathways may be suitable targets for intervention to either attenuate virus infection or enhance oncolytic potential.",2012 Dec 11,"['Berard, Alicia R.', 'Cortens, John P.', 'Krokhin, Oleg', 'Wilkins, John A.', 'Severini, Alberto', 'Coombs, Kevin M.']",PLoS One,,,True
544d61a716a23113ecb8bf04f412fbc6ba206942,PMC,Biodegradable Nanoparticle-Entrapped Vaccine Induces Cross-Protective Immune Response against a Virulent Heterologous Respiratory Viral Infection in Pigs,http://dx.doi.org/10.1371/journal.pone.0051794,PMC3519908,23240064,CC BY,"Biodegradable nanoparticle-based vaccine development research is unexplored in large animals and humans. In this study, we illustrated the efficacy of nanoparticle-entrapped UV-killed virus vaccine against an economically important respiratory viral disease of pigs called porcine reproductive and respiratory syndrome virus (PRRSV). We entrapped PLGA [poly (lactide-co-glycolides)] nanoparticles with killed PRRSV antigens (Nano-KAg) and detected its phagocytosis by pig alveolar macrophages. Single doses of Nano-KAg vaccine administered intranasally to pigs upregulated innate and PRRSV specific adaptive responses. In a virulent heterologous PRRSV challenge study, Nano-KAg vaccine significantly reduced the lung pathology and viremia, and the viral load in the lungs. Immunologically, enhanced innate and adaptive immune cell population and associated cytokines with decreased secretion of immunosuppressive mediators were observed at both mucosal sites and blood. In summary, we demonstrated the benefits of intranasal delivery of nanoparticle-based viral vaccine in eliciting cross-protective immune response in pigs, a potential large animal model.",2012 Dec 11,"['Dwivedi, Varun', 'Manickam, Cordelia', 'Binjawadagi, Basavaraj', 'Joyappa, Dechamma', 'Renukaradhya, Gourapura J.']",PLoS One,,,True
680c8cd646f4f78d97eddff21292668beba44d09,PMC,Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus,http://dx.doi.org/10.1186/1465-9921-13-43,PMC3520784,22672594,CC BY,"BACKGROUND: Influenza A virus (IAV) infection primarily targets respiratory epithelial cells and produces clinical outcomes ranging from mild upper respiratory infection to severe pneumonia. Recent studies have shown the importance of lung antioxidant defense systems against injury by IAV. Nuclear factor-erythroid 2 related factor 2 (Nrf2) activates the majority of antioxidant genes. METHODS: Alveolar type II (ATII) cells and alveolar macrophages (AM) were isolated from human lungs not suitable for transplantation and donated for medical research. In some studies ATII cells were transdifferentiated to alveolar type I-like (ATI-like) cells. Alveolar epithelial cells were infected with A/PR/8/34 (PR8) virus. We analyzed PR8 virus production, influenza A nucleoprotein levels, ROS generation and expression of antiviral genes. Immunocytofluorescence was used to determine Nrf2 translocation and western blotting to detect Nrf2, HO-1 and caspase 1 and 3 cleavage. We also analyzed ingestion of PR8 virus infected apoptotic ATII cells by AM, cytokine levels by ELISA, glutathione levels, necrosis and apoptosis by TUNEL assay. Moreover, we determined the critical importance of Nrf2 using adenovirus Nrf2 (AdNrf2) or Nrf2 siRNA to overexpress or knockdown Nrf2, respectively. RESULTS: We found that IAV induced oxidative stress, cytotoxicity and apoptosis in ATI-like and ATII cells. We also found that AM can ingest PR8 virus-induced apoptotic ATII cells (efferocytosis) but not viable cells, whereas ATII cells did not ingest these apoptotic cells. PR8 virus increased ROS production, Nrf2, HO-1, Mx1 and OAS1 expression and Nrf2 translocation to the nucleus. Nrf2 knockdown with siRNA sensitized ATI-like cells and ATII cells to injury induced by IAV and overexpression of Nrf2 with AdNrf2 protected these cells. Furthermore, Nrf2 overexpression followed by infection with PR8 virus decreased virus replication, influenza A nucleoprotein expression, antiviral response and oxidative stress. However, AdNrf2 did not increase IFN-λ1 (IL-29) levels. CONCLUSIONS: Our results indicate that IAV induces alveolar epithelial injury and that Nrf2 protects these cells from the cytopathic effects of IAV likely by increasing the expression of antioxidant genes. Identifying the pathways involved in protecting cells from injury during influenza infection may be particularly important for developing new therapeutic strategies.",2012 Jun 6,"['Kosmider, Beata', 'Messier, Elise M', 'Janssen, William J', 'Nahreini, Piruz', 'Wang, Jieru', 'Hartshorn, Kevan L', 'Mason, Robert J']",Respir Res,,,True
b0ad001bf30a7e66883a682031b9847028664e3d,PMC,Rapid production of antigen-specific monoclonal antibodies from a variety of animals,http://dx.doi.org/10.1186/1741-7007-10-80,PMC3520816,23017270,CC BY,"BACKGROUND: Although a variety of animals have been used to produce polyclonal antibodies against antigens, the production of antigen-specific monoclonal antibodies from animals remains challenging. RESULTS: We propose a simple and rapid strategy to produce monoclonal antibodies from a variety of animals. By staining lymph node cells with an antibody against immunoglobulin and a fluorescent dye specific for the endoplasmic reticulum, plasma/plasmablast cells were identified without using a series of antibodies against lineage markers. By using a fluorescently labeled antigen as a tag for a complementary cell surface immunoglobulin, antigen-specific plasma/plasmablast cells were sorted from the rest of the cell population by fluorescence-activated cell sorting. Amplification of cognate pairs of immunoglobulin heavy and light chain genes followed by DNA transfection into 293FT cells resulted in the highly efficient production of antigen-specific monoclonal antibodies from a variety of immunized animals. CONCLUSIONS: Our technology eliminates the need for both cell propagation and screening processes, offering a significant advantage over hybridoma and display strategies.",2012 Sep 28,"['Kurosawa, Nobuyuki', 'Yoshioka, Megumi', 'Fujimoto, Rika', 'Yamagishi, Fuminori', 'Isobe, Masaharu']",BMC Biol,,,True
c5f986ded9c2caf03ce509dffc7e53f93f41941c,PMC,Hexachlorophene Is a Potent KCNQ1/KCNE1 Potassium Channel Activator Which Rescues LQTs Mutants,http://dx.doi.org/10.1371/journal.pone.0051820,PMC3520906,23251633,CC BY,"The voltage-gated KCNQ1 potassium channel is expressed in cardiac tissues, and coassembly of KCNQ1 with an auxiliary KCNE1 subunit mediates a slowly activating current that accelerates the repolarization of action potential in cardiomyocytes. Mutations of KCNQ1 genes that result in reduction or loss of channel activity cause prolongation of repolarization during action potential, thereby causing long QT syndrome (LQTs). Small molecule activators of KCNQ1/KCNE1 are useful both for understanding the mechanism of the complex activity and for developing therapeutics for LQTs. In this study we report that hexachlorophene (HCP), the active component of the topical anti-infective prescription drug pHisoHex, is a KCNQ1/KCNE1 activator. HCP potently increases the current amplitude of KCNQ1/KCNE1 expressed by stabilizing the channel in an open state with an EC(50) of 4.61±1.29 μM. Further studies in cardiomyocytes showed that HCP significantly shortens the action potential duration at 1 μM. In addition, HCP is capable of rescuing the loss of function of the LQTs mutants caused by either impaired activation gating or phosphatidylinositol-4,5-bisphosphate (PIP2) binding affinity. Our results indicate HCP is a novel KCNQ1/KCNE1 activator and may be a useful tool compound for the development of LQTs therapeutics.",2012 Dec 12,"['Zheng, Yueming', 'Zhu, Xuejing', 'Zhou, Pingzheng', 'Lan, Xi', 'Xu, Haiyan', 'Li, Min', 'Gao, Zhaobing']",PLoS One,,,True
45398efb94483b10fc0547f0784cf50d6b2c7b9a,PMC,A Population Health Surveillance Theory,http://dx.doi.org/10.4178/epih/e2012007,PMC3521104,23251837,CC BY,"OBJECTIVES: Despite its extensive use, the term ""Surveillance"" often takes on various meanings in the scientific literature pertinent to public health and animal health. A critical appraisal of this literature also reveals ambiguities relating to the scope and necessary structural components underpinning the surveillance process. The authors hypothesized that these inconsistencies translate to real or perceived deficiencies in the conceptual framework of population health surveillance. This paper presents a population health surveillance theory framed upon an explicit conceptual system relative to health surveillance performed in human and animal populations. METHODS: The population health surveillance theory reflects the authors' system of thinking and was based on a creative process. RESULTS: Population health surveillance includes two broad components: one relating to the human organization (which includes expertise and the administrative program), and one relating to the system per se (which includes elements of design and method) and which can be viewed as a process. The population health surveillance process is made of five sequential interrelated steps: 1) a trigger or need, 2) problem formulation, 3) surveillance planning, 4) surveillance implementation, and 5) information communication and audit. CONCLUSIONS: The population health surveillance theory provides a systematic way of understanding, organizing and evaluating the population health surveillance process.",2012 Nov 30,"['El Allaki, Farouk', 'Bigras-Poulin, Michel', 'Michel, Pascal', 'Ravel, André']",Epidemiol Health,,,True
4dfc59a66e7a86f6a40c5fafad4c12f483ce40bc,PMC,Host-protective effect of circulating pentraxin 3 (PTX3) and complex formation with neutrophil extracellular traps,http://dx.doi.org/10.3389/fimmu.2012.00378,PMC3521240,23248627,CC BY,"Pentraxin 3 (PTX3) is a soluble pattern recognition receptor which is classified as a long-pentraxin in the pentraxin family. It is known to play an important role in innate immunity, inflammatory regulation, and female fertility. PTX3 is synthesized by specific cells, primarily in response to inflammatory signals. Among these various cells, neutrophils have a unique PTX3 production system. Neutrophils store PTX3 in neutrophil-specific granules and then the stored PTX3 is released and localizes in neutrophil extracellular traps (NETs). Although certain NET components have been identified, such as histones and anti-microbial proteins, the detailed mechanisms by which NETs localize, as well as capture and kill microbes, have not been fully elucidated. PTX3 is a candidate diagnostic marker of infection and vascular damage. In severe infectious diseases such as sepsis, the circulating PTX3 concentration increases greatly (up to 100 ng/mL, i.e., up to 100-fold of the normal level). Even though it is clearly implied that PTX3 plays a protective role in sepsis and certain other disorders, the detailed mechanisms by which it does so remain unclear. A proteomic study of PTX3 ligands in septic patients revealed that PTX3 forms a complex with certain NET component proteins. This suggests a role for PTX3 in which it facilitates the efficiency of anti-microbial protein pathogen clearance by interacting with both pathogens and anti-microbial proteins. We discuss the possible relationships between PTX3 and NET component proteins in the host protection afforded by the innate immune response. The PTX3 complex has the potential to be a highly useful diagnostic marker of sepsis and other inflammatory diseases.",2012 Dec 13,"['Daigo, Kenji', 'Hamakubo, Takao']",Front Immunol,,,True
5e3b24f55fdc84cfc263d4784c6ad6349d212866,PMC,Epimedium koreanum Nakai Water Extract Exhibits Antiviral Activity against Porcine Epidermic Diarrhea Virus In Vitro and In Vivo,http://dx.doi.org/10.1155/2012/985151,PMC3521454,23259003,CC BY,"Porcine epidemic diarrhea virus (PEDV) causes diarrhea of pigs age-independently and death of young piglets, resulting in economic loss of porcine industry. We have screened 333 natural oriental herbal medicines to search for new antiviral candidates against PEDV. We found that two herbal extracts, KIOM 198 and KIOM 124, contain significant anti-PED viral effect. KIOM 198 and KIOM 124 were identified as Epimedium koreanum Nakai and Lonicera japonica Thunberg, respectively. The further plaque and CPE inhibition assay in vitro showed that KIOM 198 has much stronger antiviral activity than KIOM 124. Additionally, KIOM 198 exhibited a similar extent of antiviral effect against other subtypes of Corona virus such as sm98 and TGE viruses. Cytotoxicity results showed that KIOM 198 is nontoxic on the cells and suggest that it can be delivered safely for therapy. Furthermore, when we orally administered KIOM 198 to piglets and then infected them with PEDV, the piglets did not show any disease symptoms like diarrhea and biopsy results showed clean intestine, whereas control pigs without KIOM 198 treatment exhibited PED-related severe symptoms. These results imply that KIOM 198 contains strong antiviral activity and has a potential to be developed as an antiviral phytomedicine to treat PEDV-related diseases in pigs.",2012 Nov 29,"['Cho, Won-Kyung', 'Kim, Hyunil', 'Choi, Yu Jeong', 'Yim, Nam-Hui', 'Yang, Hye Jin', 'Ma, Jin Yeul']",Evid Based Complement Alternat Med,,,True
0a24f22d8d49dc503c52d43dbc51459fc06fbb14,PMC,Antigenic Subversion: A Novel Mechanism of Host Immune Evasion by Ebola Virus,http://dx.doi.org/10.1371/journal.ppat.1003065,PMC3521666,23271969,CC BY,"In addition to its surface glycoprotein (GP(1,2)), Ebola virus (EBOV) directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. The generation of secreted antigens has been studied in several viruses and suggested as a mechanism of host immune evasion through absorption of antibodies and interference with antibody-mediated clearance. However such a role has not been conclusively determined for the Ebola virus sGP. In this study, we immunized mice with DNA constructs expressing GP(1,2) and/or sGP, and demonstrate that sGP can efficiently compete for anti-GP(12) antibodies, but only from mice that have been immunized by sGP. We term this phenomenon “antigenic subversion”, and propose a model whereby sGP redirects the host antibody response to focus on epitopes which it shares with membrane-bound GP(1,2), thereby allowing it to absorb anti-GP(1,2) antibodies. Unexpectedly, we found that sGP can also subvert a previously immunized host's anti-GP(1,2) response resulting in strong cross-reactivity with sGP. This finding is particularly relevant to EBOV vaccinology since it underscores the importance of eliciting robust immunity that is sufficient to rapidly clear an infection before antigenic subversion can occur. Antigenic subversion represents a novel virus escape strategy that likely helps EBOV evade host immunity, and may represent an important obstacle to EBOV vaccine design.",2012 Dec 13,"['Mohan, Gopi S.', 'Li, Wenfang', 'Ye, Ling', 'Compans, Richard W.', 'Yang, Chinglai']",PLoS Pathog,,,True
1204dc3b147d4e4d5ccc3d4aff7551d39f5fe438,PMC,Imaging Findings in Patients With H1N1 Influenza A Infection,http://dx.doi.org/10.5812/iranjradiol.4554,PMC3522360,23329946,CC BY,"BACKGROUND: Swine influenza (H1N1) is a very contagious respiratory infection and World Health Organization (WHO) has raised the alert level to phase 6 (pandemic). The study of clinical and laboratory manifestations as well as radiologic imaging findings helps in its early diagnosis. OBJECTIVES: The aim of this study was to evaluate the imaging findings of patients with documented H1N1 infection referred to our center. PATIENTS AND METHODS: Thirty-one patients (16 men) with documented H1N1 infection were included in our study. The initial radiography obtained from the patients was reviewed regarding pattern (consolidation, ground glass, nodules and reticulation), distribution (focal, multifocal, and diffuse) and the lung zones involved. Computed tomography (CT) scans were also reviewed for the same abnormalities. The patient files were studied for their possible underlying diseases. RESULTS: The mean age was 37.97 ± 13.9 years. Seventeen (54.8%) patients had co-existing condition (eight respiratory, five cardiovascular, two immunodeficiency, two cancer, four others). Twelve (38.7%) patients required intensive care unit (ICU) admission. Five (16.1%) patients died. (25.8%) had normal initial radiographs. The most common abnormality was consolidation (12/31; 38.7%) in the peripheral region (11/31; 35.5%) followed by peribronchovascular areas (10/31; 32.3%) which was most commonly observed in the lower zone. The patients admitted to the ICU were more likely to have two or more lung zones involved (P = 0.005). CONCLUSIONS: In patients with the novel swine flu infection, the most common radiographic abnormality observed was consolidation in the lower lung zones. Patients admitted to ICU were more likely to have two or more lung zones involved.",2011 Dec 25,"['Bakhshayeshkaram, Mehrdad', 'Saidi, Bahareh', 'Tabarsi, Payam', 'Zahirifard, Soheila', 'Ghofrani, Mishka']",Iran J Radiol,,,True
c47b1bf314263894ae9a5589303b7af810741267,PMC,Respiratory Viruses in Hospitalized Children with Influenza-Like Illness during the H1n1 2009 Pandemic in Sweden,http://dx.doi.org/10.1371/journal.pone.0051491,PMC3522717,23272110,CC BY,"BACKGROUND: The swine-origin influenza A(H1N1)pdm09 pandemic of 2009 had a slower spread in Europe than expected. The human rhinovirus (HRV) has been suggested to have delayed the pandemic through viral interference. The importance of co-infections over time during the pandemic and in terms of severity of the disease needs to be assessed. OBJECTIVE: The aim of this study was to investigate respiratory viruses and specifically the presence of co-infections with influenza A(H1N1)pdm09 (H1N1) in hospitalized children during the H1N1 pandemic. A secondary aim was to investigate if co-infections were associated with severity of disease. METHODS: A retrospective study was performed on 502 children with influenza-like illness admitted to inpatient care at a pediatric hospital in Stockholm, Sweden during the 6 months spanning the H1N1 pandemic in 2009. Respiratory samples were analyzed for a panel of 16 viruses by real-time polymerase chain reaction. RESULTS: One or more viruses were detected in 61.6% of the samples. Of these, 85.4% were single infections and 14.6% co-infections (2–4 viruses). The number of co-infections increased throughout the study period. H1N1 was found in 83 (16.5%) children and of these 12 (14.5%) were co-infections. HRV and H1N1 circulated to a large extent at the same time and 6.0% of the H1N1-positive children were also positive for HRV. There was no correlation between co-infections and severity of disease in children with H1N1. CONCLUSIONS: Viral co-infections were relatively common in H1N1 infected hospitalized children and need to be considered when estimating morbidity attributed to H1N1. Population-based longitudinal studies with repeated sampling are needed to improve the understanding of the importance of co-infections and viral interference.",2012 Dec 14,"['Rhedin, Samuel', 'Hamrin, Johan', 'Naucler, Pontus', 'Bennet, Rutger', 'Rotzén-Östlund, Maria', 'Färnert, Anna', 'Eriksson, Margareta']",PLoS One,,,True
05ba033423b8fcd8ca26cf0cf1611e128048f9db,PMC,Retrovirus Entry by Endocytosis and Cathepsin Proteases,http://dx.doi.org/10.1155/2012/640894,PMC3523128,23304142,CC BY,"Retroviruses include infectious agents inducing severe diseases in humans and animals. In addition, retroviruses are widely used as tools to transfer genes of interest to target cells. Understanding the entry mechanism of retroviruses contributes to developments of novel therapeutic approaches against retrovirus-induced diseases and efficient exploitation of retroviral vectors. Entry of enveloped viruses into host cell cytoplasm is achieved by fusion between the viral envelope and host cell membranes at either the cell surface or intracellular vesicles. Many animal retroviruses enter host cells through endosomes and require endosome acidification. Ecotropic murine leukemia virus entry requires cathepsin proteases activated by the endosome acidification. CD4-dependent human immunodeficiency virus (HIV) infection is thought to occur via endosomes, but endosome acidification is not necessary for the entry whereas entry of CD4-independent HIVs, which are thought to be prototypes of CD4-dependent viruses, is low pH dependent. There are several controversial results on the retroviral entry pathways. Because endocytosis and endosome acidification are complicatedly controlled by cellular mechanisms, the retrovirus entry pathways may be different in different cell lines.",2012 Dec 6,"['Kubo, Yoshinao', 'Hayashi, Hideki', 'Matsuyama, Toshifumi', 'Sato, Hironori', 'Yamamoto, Naoki']",Adv Virol,,,True
c24570f542d59b0d17450b1bd83c708f9401ca9c,PMC,Immunization with a Recombinant Vaccinia Virus That Encodes Nonstructural Proteins of the Hepatitis C Virus Suppresses Viral Protein Levels in Mouse Liver,http://dx.doi.org/10.1371/journal.pone.0051656,PMC3524174,23284733,CC BY,"Chronic hepatitis C, which is caused by infection with the hepatitis C virus (HCV), is a global health problem. Using a mouse model of hepatitis C, we examined the therapeutic effects of a recombinant vaccinia virus (rVV) that encodes an HCV protein. We generated immunocompetent mice that each expressed multiple HCV proteins via a Cre/loxP switching system and established several distinct attenuated rVV strains. The HCV core protein was expressed consistently in the liver after polyinosinic acid–polycytidylic acid injection, and these mice showed chronic hepatitis C-related pathological findings (hepatocyte abnormalities, accumulation of glycogen, steatosis), liver fibrosis, and hepatocellular carcinoma. Immunization with one rVV strain (rVV-N25), which encoded nonstructural HCV proteins, suppressed serum inflammatory cytokine levels and alleviated the symptoms of pathological chronic hepatitis C within 7 days after injection. Furthermore, HCV protein levels in liver tissue also decreased in a CD4 and CD8 T-cell-dependent manner. Consistent with these results, we showed that rVV-N25 immunization induced a robust CD8 T-cell immune response that was specific to the HCV nonstructural protein 2. We also demonstrated that the onset of chronic hepatitis in CN2-29((+/−))/MxCre((+/−)) mice was mainly attributable to inflammatory cytokines, (tumor necrosis factor) TNF-α and (interleukin) IL-6. Thus, our generated mice model should be useful for further investigation of the immunological processes associated with persistent expression of HCV proteins because these mice had not developed immune tolerance to the HCV antigen. In addition, we propose that rVV-N25 could be developed as an effective therapeutic vaccine.",2012 Dec 17,"['Sekiguchi, Satoshi', 'Kimura, Kiminori', 'Chiyo, Tomoko', 'Ohtsuki, Takahiro', 'Tobita, Yoshimi', 'Tokunaga, Yuko', 'Yasui, Fumihiko', 'Tsukiyama-Kohara, Kyoko', 'Wakita, Takaji', 'Tanaka, Toshiyuki', 'Miyasaka, Masayuki', 'Mizuno, Kyosuke', 'Hayashi, Yukiko', 'Hishima, Tsunekazu', 'Matsushima, Kouji', 'Kohara, Michinori']",PLoS One,,,True
fb3b1aad0a6c7504ba963a48906f6cbac748de77,PMC,Infectious disease aerobiology: miasma incarnate,http://dx.doi.org/10.3389/fcimb.2012.00163,PMC3525905,23267441,CC BY,,2012 Dec 19,"['Roy, Chad J.', 'Reed, Doug S.']",Front Cell Infect Microbiol,,,True
d009fdd48b7a8539c810eee5b108ca0fc6c5e6a8,PMC,"Fourth European Conference on Infections in Leukaemia (ECIL-4): Guidelines for Diagnosis and Treatment of Human Respiratory Syncytial Virus, Parainfluenza Virus, Metapneumovirus, Rhinovirus, and Coronavirus",http://dx.doi.org/10.1093/cid/cis844,PMC3526251,23024295,CC BY,"Community-acquired respiratory virus (CARV) infections have been recognized as a significant cause of morbidity and mortality in patients with leukemia and those undergoing hematopoietic stem cell transplantation (HSCT). Progression to lower respiratory tract infection with clinical and radiological signs of pneumonia and respiratory failure appears to depend on the intrinsic virulence of the specific CARV as well as factors specific to the patient, the underlying disease, and its treatment. To better define the current state of knowledge of CARVs in leukemia and HSCT patients, and to improve CARV diagnosis and management, a working group of the Fourth European Conference on Infections in Leukaemia (ECIL-4) 2011 reviewed the literature on CARVs, graded the available quality of evidence, and made recommendations according to the Infectious Diseases Society of America grading system. Owing to differences in screening, clinical presentation, and therapy for influenza and adenovirus, ECIL-4 recommendations are summarized for CARVs other than influenza and adenovirus.",2013 Jan 15,"['Hirsch, Hans H.', 'Martino, Rodrigo', 'Ward, Katherine N.', 'Boeckh, Michael', 'Einsele, Hermann', 'Ljungman, Per']",Clin Infect Dis,,,True
209fd978d66d8ffe04712de07dc7e07b779baa08,PMC,Cell-type specific requirements for thiol/disulfide exchange during HIV-1 entry and infection,http://dx.doi.org/10.1186/1742-4690-9-97,PMC3526565,23206338,CC BY,"BACKGROUND: The role of disulfide bond remodeling in HIV-1 infection is well described, but the process still remains incompletely characterized. At present, the data have been predominantly obtained using established cell lines and/or CXCR4-tropic laboratory-adapted virus strains. There is also ambiguity about which disulfide isomerases/ reductases play a major role in HIV-1 entry, as protein disulfide isomerase (PDI) and/or thioredoxin (Trx) have emerged as the two enzymes most often implicated in this process. RESULTS: We have extended our previous findings and those of others by focusing on CCR5-using HIV-1 strains and their natural targets - primary human macrophages and CD4(+) T lymphocytes. We found that the nonspecific thiol/disulfide exchange inhibitor, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), significantly reduced HIV-1 entry and infection in cell lines, human monocyte-derived macrophages (MDM), and also phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC). Subsequent studies were performed using specific anti-PDI or Trx monoclonal antibodies (mAb) in HIV-1 envelope pseudotyped and wild type (wt) virus infection systems. Although human donor-to-donor variability was observed as expected, Trx appeared to play a greater role than PDI in HIV-1 infection of MDM. In contrast, PDI, but not Trx, was predominantly involved in HIV-1 entry and infection of the CD4(+)/CCR5(+) T cell line, PM-1, and PHA-stimulated primary human T lymphocytes. Intriguingly, both PDI and Trx were present on the surface of MDM, PM-1 and PHA-stimulated CD4(+) T cells. However, considerably lower levels of Trx were detected on freshly isolated CD4(+) lymphocytes, compared to PHA-stimulated cells. CONCLUSIONS: Our findings clearly demonstrate the role of thiol/disulfide exchange in HIV-1 entry in primary T lymphocytes and MDM. They also establish a cell-type specificity regarding the involvement of particular disulfide isomerases/reductases in this process and may provide an explanation for differences among previously published studies. More importantly, from an in vivo perspective, the preferential utilization of PDI may be relevant to the HIV-1 entry and establishment of virus reservoirs in resting CD4(+) cells, while the elevated levels of Trx reported in the chronic stages of HIV-1 infection may facilitate the virus entry in macrophages and help to sustain high viremia during the decline of T lymphocytes.",2012 Dec 3,"['Stantchev, Tzanko S', 'Paciga, Mark', 'Lankford, Carla R', 'Schwartzkopff, Franziska', 'Broder, Christopher C', 'Clouse, Kathleen A']",Retrovirology,,,True
aa2d1de5f5f45ad793fffda7679200d35e971b4f,PMC,BUHO: A MATLAB Script for the Study of Stress Granules and Processing Bodies by High-Throughput Image Analysis,http://dx.doi.org/10.1371/journal.pone.0051495,PMC3527446,23284702,CC BY,"The spontaneous and reversible formation of foci and filaments that contain proteins involved in different metabolic processes is common in both the nucleus and the cytoplasm. Stress granules (SGs) and processing bodies (PBs) belong to a novel family of cellular structures collectively known as mRNA silencing foci that harbour repressed mRNAs and their associated proteins. SGs and PBs are highly dynamic and they form upon stress and dissolve thus releasing the repressed mRNAs according to changes in cell physiology. In addition, aggregates containing abnormal proteins are frequent in neurodegenerative disorders. In spite of the growing relevance of these supramolecular aggregates to diverse cellular functions a reliable automated tool for their systematic analysis is lacking. Here we report a MATLAB Script termed BUHO for the high-throughput image analysis of cellular foci. We used BUHO to assess the number, size and distribution of distinct objects with minimal deviation from manually obtained parameters. BUHO successfully addressed the induction of both SGs and PBs in mammalian and insect cells exposed to different stress stimuli. We also used BUHO to assess the dynamics of specific mRNA-silencing foci termed Smaug 1 foci (S-foci) in primary neurons upon synaptic stimulation. Finally, we used BUHO to analyze the role of candidate genes on SG formation in an RNAi-based experiment. We found that FAK56D, GCN2 and PP1 govern SG formation. The role of PP1 is conserved in mammalian cells as judged by the effect of the PP1 inhibitor salubrinal, and involves dephosphorylation of the translation factor eIF2α. All these experiments were analyzed manually and by BUHO and the results differed in less than 5% of the average value. The automated analysis by this user-friendly method will allow high-throughput image processing in short times by providing a robust, flexible and reliable alternative to the laborious and sometimes unfeasible visual scrutiny.",2012 Dec 20,"['Perez-Pepe, Marcelo', 'Slomiansky, Victoria', 'Loschi, Mariela', 'Luchelli, Luciana', 'Neme, Maximiliano', 'Thomas, María Gabriela', 'Boccaccio, Graciela Lidia']",PLoS One,,,True
b0889b0058183e21ed81e8b41414fd4cc450ce84,PMC,"Adjuvant Activity of Sargassum pallidum Polysaccharides against Combined Newcastle Disease, Infectious Bronchitis and Avian Influenza Inactivated Vaccines",http://dx.doi.org/10.3390/md10122648,PMC3528116,23342387,CC BY,"This study evaluates the effects of Sargassum pallidum polysaccharides (SPP) on the immune responses in a chicken model. The adjuvanticity of Sargassum pallidum polysaccharides in Newcastle disease (ND), infectious bronchitis (IB) and avian influenza (AI) was investigated by examining the antibody titers and lymphocyte proliferation following immunization in chickens. The chickens were administrated combined ND, IB and AI inactivated vaccines containing SPP at 10, 30 and 50 mg/mL, using an oil adjuvant vaccine as a control. The ND, IB and AI antibody titers and the lymphocyte proliferation were enhanced at 30 mg/mL SPP. In conclusion, an appropriate dose of SPP may be a safe and efficacious immune stimulator candidate that is suitable for vaccines to produce early and persistent prophylaxis.",2012 Nov 22,"['Li, Li-Jie', 'Li, Ming-Yi', 'Li, Yan-Tuan', 'Feng, Jing-Jing', 'Hao, Feng-Qiang', 'Zhang, Lun']",Mar Drugs,,,True
11588188717735eb36e684003283dbe2d9832286,PMC,"Host Cell Factors in Filovirus Entry: Novel Players, New Insights",http://dx.doi.org/10.3390/v4123336,PMC3528269,23342362,CC BY,"Filoviruses cause severe hemorrhagic fever in humans with high case-fatality rates. The cellular factors exploited by filoviruses for their spread constitute potential targets for intervention, but are incompletely defined. The viral glycoprotein (GP) mediates filovirus entry into host cells. Recent studies revealed important insights into the host cell molecules engaged by GP for cellular entry. The binding of GP to cellular lectins was found to concentrate virions onto susceptible cells and might contribute to the early and sustained infection of macrophages and dendritic cells, important viral targets. Tyrosine kinase receptors were shown to promote macropinocytic uptake of filoviruses into a subset of susceptible cells without binding to GP, while interactions between GP and human T cell Ig mucin 1 (TIM-1) might contribute to filovirus infection of mucosal epithelial cells. Moreover, GP engagement of the cholesterol transporter Niemann-Pick C1 was demonstrated to be essential for GP-mediated fusion of the viral envelope with a host cell membrane. Finally, mutagenic and structural analyses defined GP domains which interact with these host cell factors. Here, we will review the recent progress in elucidating the molecular interactions underlying filovirus entry and discuss their implications for our understanding of the viral cell tropism.",2012 Nov 26,"['Hofmann-Winkler, Heike', 'Kaup, Franziska', 'Pöhlmann, Stefan']",Viruses,,,True
2fa46e22a7460345c3a4aed5aca12df56667cb56,PMC,Innate Immunity to H5N1 Influenza Viruses in Humans,http://dx.doi.org/10.3390/v4123363,PMC3528270,23342363,CC BY,"Avian influenza virus infections in the human population are rare due to their inefficient direct human-to-human transmission. However, when humans are infected, a strong inflammatory response is usually induced, characterized by elevated levels of cytokines and chemokines in serum, believed to be important in the severe pathogenesis that develops in a high proportion of these patients. Extensive research has been performed to understand the molecular viral mechanisms involved in the H5N1 pathogenesis in humans, providing interesting insights about the virus-host interaction and the regulation of the innate immune response by these highly pathogenic viruses. In this review we summarize and discuss the most important findings in this field, focusing mainly on H5N1 virulence factors and their impact on the modulation of the innate immunity in humans.",2012 Nov 26,"['Ramos, Irene', 'Fernandez-Sesma, Ana']",Viruses,,,True
324224a860eb73492e4207926e5ea62cd1a910d9,PMC,Involvement of Autophagy in Coronavirus Replication,http://dx.doi.org/10.3390/v4123440,PMC3528273,23202545,CC BY,"Coronaviruses are single stranded, positive sense RNA viruses, which induce the rearrangement of cellular membranes upon infection of a host cell. This provides the virus with a platform for the assembly of viral replication complexes, improving efficiency of RNA synthesis. The membranes observed in coronavirus infected cells include double membrane vesicles. By nature of their double membrane, these vesicles resemble cellular autophagosomes, generated during the cellular autophagy pathway. In addition, coronavirus infection has been demonstrated to induce autophagy. Here we review current knowledge of coronavirus induced membrane rearrangements and the involvement of autophagy or autophagy protein microtubule associated protein 1B light chain 3 (LC3) in coronavirus replication.",2012 Nov 30,"['Maier, Helena J.', 'Britton, Paul']",Viruses,,,True
5e2dc7663e6a6b53d6b8f37f5ccd4e6dc0c71a57,PMC,"Epidemiology, Molecular Epidemiology and Evolution of Bovine Respiratory Syncytial Virus",http://dx.doi.org/10.3390/v4123452,PMC3528274,23202546,CC BY,"The bovine respiratory syncytial virus (BRSV) is an enveloped, negative sense, single-stranded RNA virus belonging to the pneumovirus genus within the family Paramyxoviridae. BRSV has been recognized as a major cause of respiratory disease in young calves since the early 1970s. The analysis of BRSV infection was originally hampered by its characteristic lability and poor growth in vitro. However, the advent of numerous immunological and molecular methods has facilitated the study of BRSV enormously. The knowledge gained from these studies has also provided the opportunity to develop safe, stable, attenuated virus vaccine candidates. Nonetheless, many aspects of the epidemiology, molecular epidemiology and evolution of the virus are still not fully understood. The natural course of infection is rather complex and further complicates diagnosis, treatment and the implementation of preventive measures aimed to control the disease. Therefore, understanding the mechanisms by which BRSV is able to establish infection is needed to prevent viral and disease spread. This review discusses important information regarding the epidemiology and molecular epidemiology of BRSV worldwide, and it highlights the importance of viral evolution in virus transmission.",2012 Nov 30,"['Sarmiento-Silva, Rosa Elena', 'Nakamura-Lopez, Yuko', 'Vaughan, Gilberto']",Viruses,,,True
5136621ef7ae0c8d8b2dd396e432bedceb3f0331,PMC,Identification and Characterization of a Novel Alpaca Respiratory Coronavirus Most Closely Related to the Human Coronavirus 229E,http://dx.doi.org/10.3390/v4123689,PMC3528286,23235471,CC BY,"In 2007, a novel coronavirus associated with an acute respiratory disease in alpacas (Alpaca Coronavirus, ACoV) was isolated. Full-length genomic sequencing of the ACoV demonstrated the genome to be consistent with other Alphacoronaviruses. A putative additional open-reading frame was identified between the nucleocapsid gene and 3'UTR. The ACoV was genetically most similar to the common human coronavirus (HCoV) 229E with 92.2% nucleotide identity over the entire genome. A comparison of spike gene sequences from ACoV and from HCoV-229E isolates recovered over a span of five decades showed the ACoV to be most similar to viruses isolated in the 1960’s to early 1980’s. The true origin of the ACoV is unknown, however a common ancestor between the ACoV and HCoV-229E appears to have existed prior to the 1960’s, suggesting virus transmission, either as a zoonosis or anthroponosis, has occurred between alpacas and humans.",2012 Dec 12,"['Crossley, Beate M.', 'Mock, Richard E.', 'Callison, Scott A.', 'Hietala, Sharon K.']",Viruses,,,True
1be8f67d3b7d2730be96799adfc38746474b0a3b,PMC,The effect of infection order of porcine circovirus type 2 and porcine reproductive and respiratory syndrome virus on dually infected swine alveolar macrophages,http://dx.doi.org/10.1186/1746-6148-8-174,PMC3528418,23009687,CC BY,"BACKGROUND: Concurrent infection with porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) is known as one of the major causes for porcine respiratory disease complex (PRDC). Dual infection with PCV2 and PRRSV is consistently to have more severe clinical presentations and pulmonary lesions than infection with PCV2 alone or PRRSV alone. However, it is not known if dual infections with PCV2 and PRRSV in different infection order may lead to different clinical symptoms in the host. To mimic the possible field conditions, swine alveolar macrophages (AMs) were inoculated with PCV2 and PRRSV in vitro simultaneously or with one virus 18 h earlier than the other. The cell viability, cytopathic effects, antigen-containing rates, phagocytotic and microbial killing capabilities, cytokine profiles (IL-8, TNF-α, and IFN-α) and FasL transcripts were determined, analyzed, and compared to prove the hypothesis. RESULTS: A marked reduction in PRRSV antigen-containing rate, cytopathic effect, and TNF-α expression level was revealed in AMs inoculated with PCV2 and PRRSV simultaneously and in AMs inoculated with PCV2 first then PRRSV 18 h later, but not in AMs inoculated with PRRSV first then PCV2 18 h later. Transient decrease in phagocytosis but constant reduction in microbicidal capability in AMs in the group inoculated with PCV2 alone and constant decrease in phagocytosis and microbicidal capability in AMs in all PRRSV-inoculated groups were noted. The levels of IL-8, TNF-α, IFN-α, and FasL transcripts in AMs in all groups with dual inoculation of PCV2 and PRRSV were significantly increased regardless of the infection orders as compared with infection by PCV2 alone or PRRSV alone. CONCLUSIONS: Swine AMs infected with PCV2 first then PRRSV later or infected with PCV2 and PRRSV simultaneously displayed marked reduction in PRRSV antigen-containing rate, cytopathic effect, and TNF-α expression level. The different inoculation orders of PCV2 and PRRSV in AMs leading to different results in viral antigen positivity, cytopathology, and cytokine profile may explain, at least partially, the underlying mechanism of the enhanced pulmonary lesions in PRDC exerted by dual infection with PCV2 and PRRSV and the variable clinical manifestations of PRDC-affected pigs in the field.",2012 Sep 25,"['Tsai, Yi-Chieh', 'Chang, Hui-Wen', 'Jeng, Chian-Ren', 'Lin, Tsang-Long', 'Lin, Chun-Ming', 'Wan, Cho-Hua', 'Pang, Victor Fei']",BMC Vet Res,,,True
633715b2acfa849d613285b7a01531072c2b3422,PMC,Analysis of the humoral immune responses among cynomolgus macaque naturally infected with Reston virus during the 1996 outbreak in the Philippines,http://dx.doi.org/10.1186/1746-6148-8-189,PMC3528628,23057674,CC BY,"BACKGROUND: Ebolaviruses induce lethal viral hemorrhagic fevers (VHFs) in humans and non-human primates, with the exceptions of Reston virus (RESTV), which is not pathogenic for humans. In human VHF cases, extensive analyses of the humoral immune responses in survivors and non-survivors have shown that the IgG responses to nucleoprotein (NP) and other viral proteins are associated with asymptomatic and survival outcomes, and that the neutralizing antibody responses targeting ebolaviruses glycoprotein (GP(1,2)) are the major indicator of protective immunity. On the other hand, the immune responses in non-human primates, especially naturally infected ones, have not yet been elucidated in detail, and the significance of the antibody responses against NP and GP(1,2) in RESTV-infected cynomolgus macaques is still unclear. In this study, we analyzed the humoral immune responses of cynomolgus macaque by using serum specimens obtained from the RESTV epizootic in 1996 in the Philippines to expand our knowledge on the immune responses in naturally RESTV-infected non-human primates. RESULTS: The antibody responses were analyzed using IgG-ELISA, an indirect immunofluorescent antibody assay (IFA), and a pseudotyped VSV-based neutralizing (NT) assay. Antigen-capture (Ag)-ELISA was also performed to detect viral antigens in the serum specimens. We found that the anti-GP(1,2) responses, but not the anti-NP responses, closely were correlated with the neutralization responses, as well as the clearance of viremia in the sera of the RESTV-infected cynomolgus macaques. Additionally, by analyzing the cytokine/chemokine concentrations of these serum specimens, we found high concentrations of proinflammatory cytokines/chemokines, such as IFNγ, IL8, IL-12, and MIP1α, in the convalescent phase sera. CONCLUSIONS: These results imply that both the antibody response to GP(1,2) and the proinflammatory innate responses play significant roles in the recovery from RESTV infection in cynomolgus macaques.",2012 Oct 11,"['Taniguchi, Satoshi', 'Sayama, Yusuke', 'Nagata, Noriyo', 'Ikegami, Tetsuro', 'Miranda, Mary E', 'Watanabe, Shumpei', 'Iizuka, Itoe', 'Fukushi, Shuetsu', 'Mizutani, Tetsuya', 'Ishii, Yoshiyuki', 'Saijo, Masayuki', 'Akashi, Hiroomi', 'Yoshikawa, Yasuhiro', 'Kyuwa, Shigeru', 'Morikawa, Shigeru']",BMC Vet Res,,,True
2c1d22afddf9c0d5ea6ae358aab7171b06fbdf0f,PMC,Secondary Syphilis with Pleural Effusion: Case Report and Literature Review,http://dx.doi.org/10.1155/2012/409896,PMC3530861,23304580,CC BY,"Here we present a case of a 38-year-old Indian man with a history of extramarital relationships who presented with pleurisy, skin rash, and radiological findings of pleural effusion. After thorough investigation of the etiology of his acute illness, he was found to be positive for syphilis. Review of literature revealed a small number of case reports of pleural effusion as a manifestation of secondary syphilis. The review of criteria proposed in the literature was utilized to diagnose this patient as a case of pulmonary syphilis.",2012 Dec 13,"['Elzouki, Abdel-Naser', 'Al-Kawaaz, Mustafa', 'Tafesh, Zaid']",Case Rep Infect Dis,,,True
69ef51ebe3e2ce0b8d6fc292b06b293ba2942bd7,PMC,Phylodynamic Inference and Model Assessment with Approximate Bayesian Computation: Influenza as a Case Study,http://dx.doi.org/10.1371/journal.pcbi.1002835,PMC3531293,23300420,CC BY,"A key priority in infectious disease research is to understand the ecological and evolutionary drivers of viral diseases from data on disease incidence as well as viral genetic and antigenic variation. We propose using a simulation-based, Bayesian method known as Approximate Bayesian Computation (ABC) to fit and assess phylodynamic models that simulate pathogen evolution and ecology against summaries of these data. We illustrate the versatility of the method by analyzing two spatial models describing the phylodynamics of interpandemic human influenza virus subtype A(H3N2). The first model captures antigenic drift phenomenologically with continuously waning immunity, and the second epochal evolution model describes the replacement of major, relatively long-lived antigenic clusters. Combining features of long-term surveillance data from the Netherlands with features of influenza A (H3N2) hemagglutinin gene sequences sampled in northern Europe, key phylodynamic parameters can be estimated with ABC. Goodness-of-fit analyses reveal that the irregularity in interannual incidence and H3N2's ladder-like hemagglutinin phylogeny are quantitatively only reproduced under the epochal evolution model within a spatial context. However, the concomitant incidence dynamics result in a very large reproductive number and are not consistent with empirical estimates of H3N2's population level attack rate. These results demonstrate that the interactions between the evolutionary and ecological processes impose multiple quantitative constraints on the phylodynamic trajectories of influenza A(H3N2), so that sequence and surveillance data can be used synergistically. ABC, one of several data synthesis approaches, can easily interface a broad class of phylodynamic models with various types of data but requires careful calibration of the summaries and tolerance parameters.",2012 Dec 27,"['Ratmann, Oliver', 'Donker, Gé', 'Meijer, Adam', 'Fraser, Christophe', 'Koelle, Katia']",PLoS Comput Biol,,,True
18f11e6900b1a76027c33f5e61ae9cb66d7d2370,PMC,Phylodynamic Inference and Model Assessment with Approximate Bayesian Computation: Influenza as a Case Study,http://dx.doi.org/10.1371/journal.pcbi.1002835,PMC3531293,23300420,CC BY,"A key priority in infectious disease research is to understand the ecological and evolutionary drivers of viral diseases from data on disease incidence as well as viral genetic and antigenic variation. We propose using a simulation-based, Bayesian method known as Approximate Bayesian Computation (ABC) to fit and assess phylodynamic models that simulate pathogen evolution and ecology against summaries of these data. We illustrate the versatility of the method by analyzing two spatial models describing the phylodynamics of interpandemic human influenza virus subtype A(H3N2). The first model captures antigenic drift phenomenologically with continuously waning immunity, and the second epochal evolution model describes the replacement of major, relatively long-lived antigenic clusters. Combining features of long-term surveillance data from the Netherlands with features of influenza A (H3N2) hemagglutinin gene sequences sampled in northern Europe, key phylodynamic parameters can be estimated with ABC. Goodness-of-fit analyses reveal that the irregularity in interannual incidence and H3N2's ladder-like hemagglutinin phylogeny are quantitatively only reproduced under the epochal evolution model within a spatial context. However, the concomitant incidence dynamics result in a very large reproductive number and are not consistent with empirical estimates of H3N2's population level attack rate. These results demonstrate that the interactions between the evolutionary and ecological processes impose multiple quantitative constraints on the phylodynamic trajectories of influenza A(H3N2), so that sequence and surveillance data can be used synergistically. ABC, one of several data synthesis approaches, can easily interface a broad class of phylodynamic models with various types of data but requires careful calibration of the summaries and tolerance parameters.",2012 Dec 27,"['Ratmann, Oliver', 'Donker, Gé', 'Meijer, Adam', 'Fraser, Christophe', 'Koelle, Katia']",PLoS Comput Biol,,,True
599be9828fd5c11926e88c8474f37f67f1fe4ebc,PMC,Virus-induced ER stress and the unfolded protein response,http://dx.doi.org/10.3389/fpls.2012.00293,PMC3531707,23293645,CC BY,"The accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER) results in ER stress that triggers cytoprotective signaling pathways, termed the unfolded protein response (UPR), to restore and maintain homeostasis in the ER or to induce apoptosis if ER stress remains unmitigated. The UPR signaling network encompasses three core elements, i.e., PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring protein-1 (IRE1). Activation of these three branch pathways of the UPR leads to the translation arrest and degradation of misfolded proteins, the expression of ER molecular chaperones, and the expansion of the ER membrane to decrease the load of proteins and increase the protein-folding capacity in the ER. Recently, the essential roles of the UPR have been implicated in a number of mammalian diseases, particularly viral diseases. In virus-infected cells, the cellular translation machinery is hijacked by the infecting virus to produce large amounts of viral proteins, which inevitably perturbs ER homeostasis and causes ER stress. This review summarizes current knowledge about the UPR signaling pathways, highlights two identified UPR pathways in plants, and discuss progress in elucidating the UPR in virus-infected cells and its functional roles in viral infection.",2012 Dec 28,"['Zhang, Lingrui', 'Wang, Aiming']",Front Plant Sci,,,True
a4ffcadecc4b60c30df8f699c480724523272e62,PMC,First Discovery and Stucture-Activity Relationship Study of Phenanthroquinolizidines as Novel Antiviral Agents against Tobacco Mosaic Virus (TMV),http://dx.doi.org/10.1371/journal.pone.0052933,PMC3532156,23285230,CC BY,"A series of phenanthroquinolizidine alkaloids 1–24 were prepared and first evaluated for their antiviral activity against tobacco mosaic virus (TMV). The bioassay results showed that most of these compounds exhibited good to excellent in vivo anti-TMV activity, of which compounds 1, 2, 15 and 16 displayed significantly higher activity than (R)-antofine and commercial Ningnanmycin at the same test condition. The substituents on the phenanthrene moiety play an important role for maintaining high in vivo antiviral activity. The introduction of 6-hydroxyl, which is proposed to interact with TMV RNA, did increased anti-TMV activity. The 14aR-configuration was confirmed to be the preferred antiviral configuration for phenanthroquinolizidine alkaloids. Introduction of hydroxy group at 15-position of phenanthroquinolizidine alkaloids increased activity for S-configuration but decreased activity for R-configuration. Present study provides fundamental support for development and optimization of phenanthroquinolizidine alkaloids as potential inhibitors of plant virus.",2012 Dec 28,"['Wang, Ziwen', 'Feng, Anzheng', 'Cui, Mingbo', 'Liu, Yuxiu', 'Wang, Lizhong', 'Wang, Qingmin']",PLoS One,,,True
12fc7df6445be6360090621b75df383ce86772af,PMC,Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models,http://dx.doi.org/10.1186/1472-6882-12-237,PMC3533872,23190501,CC BY,"BACKGROUND: Cinnamon bark is one of the most popular herbal ingredients in traditional oriental medicine and possesses diverse pharmacological activities including anti-bacterial, anti-viral, and anti-cancer properties. The goal of this study is to investigate the in vivo and in vitro inhibitory effect of cinnamon water extract (CWE) on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and its underlying intracellular mechanisms. METHODS: CWE was orally administrated to mice for 6 days prior to intraperitoneal injection of LPS. Serum levels of TNF-α and interleukin (IL)-6 were determined 1 hour after LPS stimulation. Peritoneal macrophages from thioglycollate-injected mice were isolated and assayed for viability, cytokine expression and signaling molecules upon LPS stimulation. CWE was further fractioned according to molecular size, and the levels of total polyphenols and biological activities of each fraction were measured. RESULTS: The oral administration of CWE to mice significantly decreased the serum levels of TNF-α and IL-6. CWE treatment in vitro decreased the mRNA expression of TNF-α. CWE blocked the LPS-induced degradation of IκBα as well as the activation of JNK, p38 and ERK1/2. Furthermore, size-based fractionation of CWE showed that the observed inhibitory effect of CWE in vitro occurred in the fraction containing the highest level of total polyphenols. CONCLUSIONS: Treatment with CWE decreased LPS-induced TNF-α in serum. In vitro inhibition of TNF-α gene by CWE may occur via the modulation of IκBα degradation and JNK, p38, and ERK1/2 activation. Our results also indicate that the observed anti-inflammatory action of CWE may originate from the presence of polyphenols.",2012 Nov 28,"['Hong, Joung-Woo', 'Yang, Ga-Eun', 'Kim, Yoon Bum', 'Eom, Seok Hyun', 'Lew, Jae-Hwan', 'Kang, Hee']",BMC Complement Altern Med,,,True
e11512bdc7871914c25d4ba5b098979d34123c34,PMC,Effectiveness of Integrated HIV Prevention Interventions among Chinese Men Who Have Sex with Men: Evaluation of a 16-City Public Health Program,http://dx.doi.org/10.1371/journal.pone.0050873,PMC3534092,23300528,CC BY,"To examine the impacts of a multi-city HIV prevention public health program (China Global Fund Round 5 Project) on condom use and HIV infection, we analyzed four yearly cross-sectional surveys from 2006 through 2009 among 20,843 men who have sex with men (MSM) in 16 Chinese cities. Self-reported condom use at last sex with a male partner increased from 58% in 2006 to 81% in 2009 (trend test, P<0.001). HIV prevalence increased from 2.3% in 2006 to 5.3% in 2009 (P<0.001). Multivariable logistic regression analysis showed that self-reported receipt of interventions was an independent predictor of increased condom use at last sex with a male partner over time (adjusted odds ratio [aOR], 1.63 in 2006 to 2.33 in 2009; P<0.001), and lower HIV prevalence (aOR, 1.08 in 2006 to 0.45 in 2009; P<0.001). HIV prevalence increased from 2006–2009 for participants with no self-reported receipt of interventions (2.1% in 2006 to 10.3% in 2009) and less so for those with interventions (2.4% to 4.7%). This Chinese public health program had positive impacts on both behaviors and disease rate among MSM population. Escalation of the coverage and intensity of effective interventions is needed for further increasing condom use and for reversing the rising trend of HIV epidemic.",2012 Dec 31,"['Ye, Shaodong', 'Xiao, Yan', 'Jin, Canrui', 'Cassell, Holly', 'Blevins, Meridith', 'Sun, Jiangping', 'Vermund, Sten H.', 'Qian, Han-Zhu']",PLoS One,,,True
a94e4109b44346c490243c71fd533cd1a9fd047c,PMC,Anti-HBV efficacy of combined siRNAs targeting viral gene and heat shock cognate 70,http://dx.doi.org/10.1186/1743-422X-9-275,PMC3534549,23158906,CC BY,"BACKGROUND: Hepatitis B virus (HBV) infection is a major health concern with more than two billion individuals currently infected worldwide. Because of the limited effectiveness of existing vaccines and drugs, development of novel antiviral strategies is urgently needed. Heat stress cognate 70 (Hsc70) is an ATP-binding protein of the heat stress protein 70 family. Hsc70 has been found to be required for HBV DNA replication. Here we report, for the first time, that combined siRNAs targeting viral gene and siHsc70 are highly effective in suppressing ongoing HBV expression and replication. METHODS: We constructed two plasmids (S1 and S2) expressing short hairpin RNAs (shRNAs) targeting surface open reading frame of HBV(HBVS) and one plasmid expressing shRNA targeting Hsc70 (siHsc70), and we used the EGFP-specific siRNA plasmid (siEGFP) as we had previously described. First, we evaluated the gene-silencing efficacy of both shRNAs using an enhanced green fluorescent protein (EGFP) reporter system and flow cytometry in HEK293 and T98G cells. Then, the antiviral potencies of HBV-specific siRNA (siHBV) in combination with siHsc70 in HepG2.2.15 cells were investigated. Moreover, type I IFN and TNF-α induction were measured by quantitative real-time PCR and ELISA. RESULTS: Cotransfection of either S1 or S2 with an EGFP plasmid produced an 80%–90% reduction in EGFP signal relative to the control. This combinational RNAi effectively and specifically inhibited HBV protein, mRNA and HBV DNA, resulting in up to a 3.36 log(10) reduction in HBV load in the HepG2.2.15 cell culture supernatants. The combined siRNAs were more potent than siHBV or siHsc70 used separately, and this approach can enhance potency in suppressing ongoing viral gene expression and replication in HepG2.2.15 cells while forestalling escape by mutant HBV. The antiviral synergy of siHBV used in combination with siHsc70 produced no cytotoxicity and induced no production of IFN-α, IFN-β and TNF-α in transfected cells. CONCLUSIONS: Our combinational RNAi was sequence-specific, effective against wild-type and mutant drug-resistant HBV strains, without triggering interferon response or producing any side effects. These findings indicate that combinational RNAi has tremendous promise for developing innovative therapy against viral infection.",2012 Nov 16,"['Bian, Zhongqi', 'Xiao, An', 'Cao, Mingmei', 'Liu, Mingqiu', 'Liu, Shuang', 'Jiao, Ye', 'Yan, Weiyao', 'Qi, Zhongtian', 'Zheng, Zhaoxin']",Virol J,,,True
009002e8a66b8c1df088cf04069629fd76b13bb9,PMC,Epidemiological Characteristics of Imported Influenza A (H1N1) Cases during the 2009 Pandemic in Korea,http://dx.doi.org/10.4178/epih/e2012009,PMC3535160,23316418,CC BY,"OBJECTIVES: Quarantine measure for prevention of epidemic disease and further evaluations of their efficiency are possible only by elaborating analyses of imported cases. The purpose of this study was to analyze descriptive epidemiological characteristics of pandemic influenza A (H1N1) cases imported to Korea. METHODS: We collected two sets of data. The first set, comprised daily reported cases of H1N1 obtained from local cities in accordance with government policy about mandatory reporting of all H1N1 cases during May 1 to August 19, 2009. The second set, including 372 confirmed imported H1N1 cases, identified from 13 National Quarantine Stations in the Korea Centers for Disease Control and Prevention from May 24 to December 31, 2009. However, given the lack of information on the nature of the imported H1N1 cases from the two data sets during the over lapping period from May 24 to August 19, we express the number of imported cases as a range for this period. RESULTS: We estimated that the number of imported H1N1 cases from May 1 to August 19, 2009, was between 1,098 and 1,291 and the total number of cases was 2,409 to 2,580. We found the number of imported cases was beginning to diminish as of August. A analysis of the second data set showed that the distribution of sex was similar (males 50.7%, females 49.3%) and the age distribution from 20 to 59 was 61.5% and that of 60 and over was 0.8% of the 372 cases. We identified 25 countries where people infected with H1N1 traveled and 67.5% were in Asia. But the proportion of cases (/1,000) by region shows Oceania (0.199), South America (0.118), Southeast Asia (0.071), North America (0.049), Europe (0.035), and Northeast Asia (0.016) in that order. The order of H1N1 peaking was the Southern Hemisphere, Tropics, and the Nothern Hemisphere. CONCLUSIONS: This study provided information that could make possible the evaluation of the government quarantine measure for stopping imported disease from causing community-acquired spread in the future.",2012 Dec 31,"['Choi, Jun Kil', 'Lee, Sang Won', 'Choi, Bo Youl']",Epidemiol Health,,,True
725b175750813a29f16faee9a389ed706eba5ae4,PMC,The 19 kDa Mycobacterium tuberculosis Lipoprotein (LpqH) Induces Macrophage Apoptosis through Extrinsic and Intrinsic Pathways: A Role for the Mitochondrial Apoptosis-Inducing Factor,http://dx.doi.org/10.1155/2012/950503,PMC3536062,23316255,CC BY,"We describe the association of caspase-dependent and caspase-independent mechanisms in macrophage apoptosis induced by LpqH, a 19 kDa Mycobacterium tuberculosis lipoprotein. LpqH triggered TLR2 activation, with upregulation of death receptors and ligands, which was followed by a death receptor signaling cascade with activation of initiator caspase 8 and executioner caspase 3. In this caspase-mediated phase, mitochondrial factors were involved in loss of mitochondrial transmembrane potential (ΔΨm), release of cytochrome c, and caspase 9 activation. Interestingly, a caspase-independent pathway was also identified; by immunoblot, the mitochondrial apoptosis inducing factor (AIF) was demonstrated in nuclei and cytosol of LpqH-treated macrophages. Confocal microscopy revealed translocation of AIF to the nuclei of the majority of apoptotic cells. These findings emphasize the complex and redundant nature of the macrophage death response to mycobacteria.",2012 Dec 19,"['Sánchez, Alejandro', 'Espinosa, Patricia', 'García, Teresa', 'Mancilla, Raúl']",Clin Dev Immunol,,,True
ef64fa65c77a221698f7cf13acdcf801ed2d554b,PMC,A novel strategy for efficient production of anti-V3 human scFvs against HIV-1 clade C,http://dx.doi.org/10.1186/1472-6750-12-87,PMC3536577,23153214,CC BY,"BACKGROUND: Production of human monoclonal antibodies that exhibit broadly neutralizing activity is needed for preventing HIV-1 infection, however only a few such antibodies have been generated till date. Isolation of antibodies by the hybridoma technology is a cumbersome process with fewer yields. Further, the loss of unstable or slowly growing clones which may have unique binding specificities often occurs during cloning and propagation and the strongly positive clones are often lost. This has been avoided by the process described in this paper, wherein, by combining the strategy of EBV transformation and recombinant DNA technology, we constructed human single chain variable fragments (scFvs) against the third variable region (V3) of the clade C HIV-1 envelope. RESULTS: An antigen specific phage library of 7000 clones was constructed from the enriched V3- positive antibody secreting EBV transformed cells. By ligation of the digested scFv DNA into phagemid vector and bio panning against the HIV-1 consensus C and B V3 peptides followed by random selection of 40 clones, we identified 15 clones that showed V3 reactivity in phage ELISA. DNA fingerprinting analysis and sequencing showed that 13 out of the 15 clones were distinct. Expression of the positive clones was tested by SDS-PAGE and Western blot. All the 13 anti-V3 scFvs showed cross-reactivity against both the clade C and B V3 peptides and did not show any reactivity against other unrelated peptides in ELISA. Preliminary neutralization assays indicated varying degrees of neutralization of clade C and B viruses. EBV transformation, followed by antigen selection of lines to identify specific binders, enabled the selection of phage from un-cloned lines for scFv generation, thus avoiding the problems of hybridoma technology. Moreover, as the clones were pretested for antigen binding, a comparatively small library sufficed for the selection of a considerable number of unique antigen binding phage. After selection, the phage clones were propagated in a clonal manner. CONCLUSIONS: This strategy can be efficiently used and is cost effective for the generation of diverse recombinant antibodies. This is the first study to generate anti-V3 scFvs against HIV-1 Clade C.",2012 Nov 15,"['Kumar, Rajesh', 'Andrabi, Raiees', 'Tiwari, Ashutosh', 'Prakash, Somi Sankaran', 'Wig, Naveet', 'Dutta, Durgashree', 'Sankhyan, Anurag', 'Khan, Lubina', 'Sinha, Subrata', 'Luthra, Kalpana']",BMC Biotechnol,,,True
bc5761e9d769b9fb1e723e1932ee3c5d4e21bd0a,PMC,Stimulation with a class A CpG oligonucleotide enhances resistance to infection with feline viruses from five different families,http://dx.doi.org/10.1186/1297-9716-43-60,PMC3537549,22906110,CC BY,"Domestic cats are commonly affected by viral pathogens that induce lengthy infections with fatal outcomes. Prevention of viral propagation is of primordial importance in shelters and catteries, where cats from different backgrounds have narrow contacts. Oligonucleotides (ODN) containing cytosine-phosphate-guanosine motifs of class A (CpG-A) are highly potent synthetic inducers of innate antiviral mechanisms. The aim of this study was to test their ability to modulate innate immune responses and prevent viral replication as stand-alone agents in the domestic cat. CpG-A stimulation of feline peripheral blood mononuclear cells (PBMCs) enhanced their proliferation, increased the presence of co-stimulatory molecules on their surface and influenced their gene expression profiles in an antiviral orientation. Incubation of the supernatants of CpG-A stimulated PBMCs with feline cell lines of epithelial and fibroblastic origin induced expression of the antiviral myxovirus resistance (Mx) gene in these target cells, which also showed enhanced resistance to feline viruses from five distinct families, namely Coronaviridae, Herpesviridae, Caliciviridae, Parvoviridae, and Retroviridae. Most importantly, subcutaneous administration of CpG-A in domestic cats systemically increased the expression of Mx, reaching maximal levels within 24 h. Plasma from treated cats could furthermore inhibit viral replication in vitro. Altogether, our data highlight the promising potential of CpG-A to induce a preventive antiviral state in the cat and to protect feline populations against a broad range of virus infections.",2012 Aug 20,"['Robert-Tissot, Céline', 'Rüegger, Vera L', 'Cattori, Valentino', 'Meli, Marina L', 'Riond, Barbara', 'Moore, Peter F', 'Engels, Monika', 'Franchini, Marco', 'Hofmann-Lehmann, Regina', 'Lutz, Hans']",Vet Res,,,True
0e5c57371f4f2cf8e3d56871a391c25ee43aaa4f,PMC,Lycorine induces cell-cycle arrest in the G0/G1 phase in K562 cells via HDAC inhibition,http://dx.doi.org/10.1186/1475-2867-12-49,PMC3537594,23176676,CC BY,"BACKGROUND: Lycorine, a natural alkaloid extracted from Amaryllidaceae, has shown various pharmacological effects. Recent studies have focused on the potential antitumor activity of lycorine. In our previous study, we found that lycorine decrease the cell viability of leukemia HL-60 cells and multiple myeloma KM3 cells and induces cell apoptosis. However, the effect and molecular mechanism of lycorine on human chronic myelocytic leukemia cells has yet to be determined. METHODS: Human chronic myelocytic leukemia cells K562 were treated with lycorine. Cell viability was monitored using the method of CCK-8. The histone deacetylase (HDAC) enzymatic activity was detected by HDAC colorimetric assay, and the cell cycle was analyzed by flow cytometry. The expression of cell-cycle related proteins were identified using Western blot. RESULTS: In the present study, we further revealed that lycorine can inhibit the proliferation of K562 cells. Analysis of HDAC activity showed that lycroine decreases HDAC enzymatic activities in K562 cells in a dose-dependent manner. Inhibition of HDAC activity has been associated with cell-cycle arrest and growth inhibition. We evaluated the cell cycle distribution after lycorine treatment and found that lycorine causes cell-cycle arrest in the G0/G1 phase. To investigate the mechanism behind this cell cycle arrest, G1-related proteins were assayed by Western blot. After lycorine treatment, cyclin D1 and cyclin-dependent kinase 4 expressions were inhibited and retinoblastoma protein phosphorylation was reduced. Lycorine treatment also significantly upregulated the expression of p53 and its target gene product, p21. CONCLUSIONS: These results suggest that inhibition of HDAC activity is responsible for at least part of the induction of cell-cycle arrest in the G0/G1 phase by lycorine and provide a mechanistic framework for further exploring the use of lycorine as a novel antitumor agent.",2012 Nov 23,"['Li, Lv', 'Dai, Hong-Juan', 'Ye, Mao', 'Wang, Shu-Ling', 'Xiao, Xiao-Juan', 'Zheng, Jie', 'Chen, Hui-Yong', 'Luo, Yu-hao', 'Liu, Jing']",Cancer Cell Int,,,True
957d77501f48dcd482bfa9491c169ffb781a3277,PMC,Low Levels of Mannan-Binding Lectin or Ficolins Are Not Associated with an Increased Risk of Cytomegalovirus Disease in HIV-Infected Patients,http://dx.doi.org/10.1371/journal.pone.0051983,PMC3537714,23308103,CC BY,"BACKGROUND: In HIV-infected patients, prediction of Cytomegalovirus (CMV) disease remains difficult. A protective role of mannan-binding lectin (MBL) and ficolins against CMV disease has been reported after transplantation, but the impact in HIV-infected patients is unclear. METHODS: In a case-control study nested within the Swiss HIV Cohort Study, we investigated associations between plasma levels of MBL/ficolins and CMV disease. We compared HIV-infected patients with CMV disease (cases) to CMV-seropositive patients without CMV disease (controls) matched for CD4 T-cells, sampling time, and use of combination antiretroviral therapy. MBL and M-ficolin, L-ficolin, and H-ficolin were quantified using ELISA. RESULTS: We analysed 105 cases and 105 matched controls. CMV disease was neither associated with MBL (odds ratio [OR] 1.03 per log(10) ng/mL increase (95% CI 0.73–1.45)) nor with ficolins (OR per log(10) ng/mL increase 0.66 (95% CI 0.28–1.52), 2.34 (95% CI 0.44–12.36), and 0.89 (95% CI 0.26–3.03) for M-ficolin, L-ficolin, and H-ficolin, respectively). We found no evidence of a greater association between MBL and CMV disease in patients with low CD4 counts; however in the multivariable analysis, CMV disease was more likely in patients with an increased HIV RNA (OR 1.53 per log(10) copies/mL; 95% CI 1.08–2.16), or a shorter duration of HIV-infection (OR 0.91 per year; 95% CI 0.84–0.98). CONCLUSIONS: CMV disease is not associated with low levels of MBL/ficolins, suggesting a lack of a protective role in HIV-infected patients.",2013 Jan 4,"['Egli, Adrian', 'Schäfer, Juliane', 'Osthoff, Michael', 'Thiel, Steffen', 'Mikkelsen, Christina', 'Rauch, Andri', 'Hirsch, Hans H.', 'Bucher, Heiner C.', 'Young, James', 'Jensenius, Jens C.', 'Battegay, Manuel', 'Trendelenburg, Marten', None]",PLoS One,,,True
415ccc587d634fc429ac080cf06694f78621ef73,PMC,"Household transmission of respiratory viruses – assessment of viral, individual and household characteristics in a population study of healthy Australian adults",http://dx.doi.org/10.1186/1471-2334-12-345,PMC3538067,23231698,CC BY,"BACKGROUND: Household transmission of influenza-like illness (ILI) may vary with viral and demographic characteristics. We examined the effect of these factors in a population-based sample of adults with ILI. METHODS: We conducted a prospective cohort study in community-dwelling Australian adults nested within an influenza vaccine effectiveness trial. On presentation with ILI, participants were swabbed for a range of respiratory viruses and asked to return a questionnaire collecting details of household members with or without similar symptoms. We used logistic and Poisson regression to assess the key characteristics of household transmission. RESULTS: 258 participants from multi-occupancy households experienced 279 ILI episodes and returned a questionnaire. Of these, 183 were the primary case in the household allowing assessment of factors associated with transmission. Transmission was significantly associated in univariate analyses with female sex (27% vs. 13%, risk ratio (RR) = 2.13 (1.08, 4.21)) and the presence of a child in the house (33% vs. 17%, RR = 1.90 (1.11, 3.26)). The secondary household attack proportion (SHAP) was 0.14, higher if influenza was isolated (RR = 2.1 (1.0, 4.5)). Vaccinated participants who nonetheless became infected with influenza had a higher SHAP (Incidence RR = 5.24 (2.17, 12.6)). CONCLUSIONS: The increased SHAP in households of vaccinated participants who nonetheless had confirmed influenza infection supports the hypothesis that in years of vaccine mismatch, not only is influenza vaccine less protective for the vaccine recipient, but that the population’s immunity is also lower.",2012 Dec 11,"['McCaw, James M', 'Howard, Peter F', 'Richmond, Peter C', 'Nissen, Michael', 'Sloots, Theo', 'Lambert, Stephen B', 'Lai, Michael', 'Greenberg, Michael', 'Nolan, Terry', 'McVernon, Jodie']",BMC Infect Dis,,,True
af9203fc2b757d830121abc6c7043614b6e9baad,PMC,"Household transmission of respiratory viruses – assessment of viral, individual and household characteristics in a population study of healthy Australian adults",http://dx.doi.org/10.1186/1471-2334-12-345,PMC3538067,23231698,CC BY,"BACKGROUND: Household transmission of influenza-like illness (ILI) may vary with viral and demographic characteristics. We examined the effect of these factors in a population-based sample of adults with ILI. METHODS: We conducted a prospective cohort study in community-dwelling Australian adults nested within an influenza vaccine effectiveness trial. On presentation with ILI, participants were swabbed for a range of respiratory viruses and asked to return a questionnaire collecting details of household members with or without similar symptoms. We used logistic and Poisson regression to assess the key characteristics of household transmission. RESULTS: 258 participants from multi-occupancy households experienced 279 ILI episodes and returned a questionnaire. Of these, 183 were the primary case in the household allowing assessment of factors associated with transmission. Transmission was significantly associated in univariate analyses with female sex (27% vs. 13%, risk ratio (RR) = 2.13 (1.08, 4.21)) and the presence of a child in the house (33% vs. 17%, RR = 1.90 (1.11, 3.26)). The secondary household attack proportion (SHAP) was 0.14, higher if influenza was isolated (RR = 2.1 (1.0, 4.5)). Vaccinated participants who nonetheless became infected with influenza had a higher SHAP (Incidence RR = 5.24 (2.17, 12.6)). CONCLUSIONS: The increased SHAP in households of vaccinated participants who nonetheless had confirmed influenza infection supports the hypothesis that in years of vaccine mismatch, not only is influenza vaccine less protective for the vaccine recipient, but that the population’s immunity is also lower.",2012 Dec 11,"['McCaw, James M', 'Howard, Peter F', 'Richmond, Peter C', 'Nissen, Michael', 'Sloots, Theo', 'Lambert, Stephen B', 'Lai, Michael', 'Greenberg, Michael', 'Nolan, Terry', 'McVernon, Jodie']",BMC Infect Dis,,,False
25d4af008525a27cff170cac5381937b1a65dc83,PMC,Viral etiologies of lower respiratory tract infections among Egyptian children under five years of age,http://dx.doi.org/10.1186/1471-2334-12-350,PMC3538156,23237512,CC BY,"BACKGROUND: Lower respiratory tract infections (LRTI) are responsible for a considerable number of deaths among children, particularly in developing countries. In Egypt and the Middle East region, there is a lack of data regarding the viral causes of LRTI. In this study, we aimed to identify the relative prevalence of various respiratory viruses that contribute to LRTIs in young children. Although, nucleic acid-based methods have gained importance as a sensitive tool to determine the viral infections, their use is limited because of their prohibitive cost in low-income countries. Therefore, we applied three different laboratory methods, and presented the different virus prevalence patterns detected by each method. METHODS: We collected nasopharyngeal aspirate samples, demographic data and, clinical data from 450 children under five years of age who presented with LRTI at Abou El Reesh hospital in Cairo during a one-year period. To identify the viral causes of the LRTI we used direct fluorescence assay, real-time reverse-transcriptase polymerase chain reaction (rt-RT-PCR), and shell vial culture. We tested for eight major respiratory viruses. RESULTS: Two hundred sixty-nine patients (59.9%) had a viral infection, among which 10.8% had a co-infection with two or more viruses. By all three methods, respiratory syncytial virus (RSV) was the most predominant, and parainfluenza virus type 2 (HPIV-2), influenza B virus (FLUBV) were the least predominant. Other viral prevalence patterns differed according to the detection method used. The distribution of various viruses among different age groups and seasonal distribution of the viruses were also determined. CONCLUSIONS: RSV and human adenovirus were the most common respiratory viruses detected by rt-RT-PCR. Co-infections were found to be frequent among children and the vast majority of co-infections were detected by nucleic acid-based detection assays.",2012 Dec 13,"['Shafik, Caroline F', 'Mohareb, Emad W', 'Yassin, Aymen S', 'Amin, Madgy A', 'El Kholy, Amani', 'El-Karaksy, Hanaa', 'Youssef, Fouad G']",BMC Infect Dis,,,True
ec645bdfc64cfa6c23a1cf9bf56950c2f9348ec1,PMC,Viral etiologies of lower respiratory tract infections among Egyptian children under five years of age,http://dx.doi.org/10.1186/1471-2334-12-350,PMC3538156,23237512,CC BY,"BACKGROUND: Lower respiratory tract infections (LRTI) are responsible for a considerable number of deaths among children, particularly in developing countries. In Egypt and the Middle East region, there is a lack of data regarding the viral causes of LRTI. In this study, we aimed to identify the relative prevalence of various respiratory viruses that contribute to LRTIs in young children. Although, nucleic acid-based methods have gained importance as a sensitive tool to determine the viral infections, their use is limited because of their prohibitive cost in low-income countries. Therefore, we applied three different laboratory methods, and presented the different virus prevalence patterns detected by each method. METHODS: We collected nasopharyngeal aspirate samples, demographic data and, clinical data from 450 children under five years of age who presented with LRTI at Abou El Reesh hospital in Cairo during a one-year period. To identify the viral causes of the LRTI we used direct fluorescence assay, real-time reverse-transcriptase polymerase chain reaction (rt-RT-PCR), and shell vial culture. We tested for eight major respiratory viruses. RESULTS: Two hundred sixty-nine patients (59.9%) had a viral infection, among which 10.8% had a co-infection with two or more viruses. By all three methods, respiratory syncytial virus (RSV) was the most predominant, and parainfluenza virus type 2 (HPIV-2), influenza B virus (FLUBV) were the least predominant. Other viral prevalence patterns differed according to the detection method used. The distribution of various viruses among different age groups and seasonal distribution of the viruses were also determined. CONCLUSIONS: RSV and human adenovirus were the most common respiratory viruses detected by rt-RT-PCR. Co-infections were found to be frequent among children and the vast majority of co-infections were detected by nucleic acid-based detection assays.",2012 Dec 13,"['Shafik, Caroline F', 'Mohareb, Emad W', 'Yassin, Aymen S', 'Amin, Madgy A', 'El Kholy, Amani', 'El-Karaksy, Hanaa', 'Youssef, Fouad G']",BMC Infect Dis,,,False
ec541d386273c4ba8629d3bebf20e7ffa635aeac,PMC,Viral etiologies of lower respiratory tract infections among Egyptian children under five years of age,http://dx.doi.org/10.1186/1471-2334-12-350,PMC3538156,23237512,CC BY,"BACKGROUND: Lower respiratory tract infections (LRTI) are responsible for a considerable number of deaths among children, particularly in developing countries. In Egypt and the Middle East region, there is a lack of data regarding the viral causes of LRTI. In this study, we aimed to identify the relative prevalence of various respiratory viruses that contribute to LRTIs in young children. Although, nucleic acid-based methods have gained importance as a sensitive tool to determine the viral infections, their use is limited because of their prohibitive cost in low-income countries. Therefore, we applied three different laboratory methods, and presented the different virus prevalence patterns detected by each method. METHODS: We collected nasopharyngeal aspirate samples, demographic data and, clinical data from 450 children under five years of age who presented with LRTI at Abou El Reesh hospital in Cairo during a one-year period. To identify the viral causes of the LRTI we used direct fluorescence assay, real-time reverse-transcriptase polymerase chain reaction (rt-RT-PCR), and shell vial culture. We tested for eight major respiratory viruses. RESULTS: Two hundred sixty-nine patients (59.9%) had a viral infection, among which 10.8% had a co-infection with two or more viruses. By all three methods, respiratory syncytial virus (RSV) was the most predominant, and parainfluenza virus type 2 (HPIV-2), influenza B virus (FLUBV) were the least predominant. Other viral prevalence patterns differed according to the detection method used. The distribution of various viruses among different age groups and seasonal distribution of the viruses were also determined. CONCLUSIONS: RSV and human adenovirus were the most common respiratory viruses detected by rt-RT-PCR. Co-infections were found to be frequent among children and the vast majority of co-infections were detected by nucleic acid-based detection assays.",2012 Dec 13,"['Shafik, Caroline F', 'Mohareb, Emad W', 'Yassin, Aymen S', 'Amin, Madgy A', 'El Kholy, Amani', 'El-Karaksy, Hanaa', 'Youssef, Fouad G']",BMC Infect Dis,,,False
bcd9208e1cff6a9d5e3af17745299ceea1479529,PMC,Purification and Characterisation of Immunoglobulins from the Australian Black Flying Fox (Pteropus alecto) Using Anti-Fab Affinity Chromatography Reveals the Low Abundance of IgA,http://dx.doi.org/10.1371/journal.pone.0052930,PMC3538733,23308125,CC BY,"There is now an overwhelming body of evidence that implicates bats in the dissemination of a long list of emerging and re-emerging viral agents, often causing illnesses or death in both animals and humans. Despite this, there is a paucity of information regarding the immunological mechanisms by which bats coexist with highly pathogenic viruses. Immunoglobulins are major components of the adaptive immune system. Early studies found bats may have quantitatively lower antibody responses to model antigens compared to conventional laboratory animals. To further understand the antibody response of bats, the present study purified and characterised the major immunoglobulin classes from healthy black flying foxes, Pteropus alecto. We employed a novel strategy, where IgG was initially purified and used to generate anti-Fab specific antibodies. Immobilised anti-Fab specific antibodies were then used to capture other immunoglobulins from IgG depleted serum. While high quantities of IgM were successfully isolated from serum, IgA was not. Only trace quantities of IgA were detected in the serum by mass spectrometry. Immobilised ligands specific to IgA (Jacalin, Peptide M and staphylococcal superantigen-like protein) also failed to capture P. alecto IgA from serum. IgM was the second most abundant serum antibody after IgG. A survey of mucosal secretions found IgG was the dominant antibody class rather than IgA. Our study demonstrates healthy P. alecto bats have markedly less serum IgA than expected. Higher quantities of IgG in mucosal secretions may be compensation for this low abundance or lack of IgA. Knowledge and reagents developed within this study can be used in the future to examine class-specific antibody response within this important viral host.",2013 Jan 7,"['Wynne, James W.', 'Di Rubbo, Antonio', 'Shiell, Brian J.', 'Beddome, Gary', 'Cowled, Christopher', 'Peck, Grantley R.', 'Huang, Jing', 'Grimley, Samantha L.', 'Baker, Michelle L.', 'Michalski, Wojtek P.']",PLoS One,,,True
45edbd85cb93950fecbc8da86f684a9e45c1d8f1,PMC,Inhibitory Influence of Enterococcus faecium on the Propagation of Swine Influenza A Virus In Vitro,http://dx.doi.org/10.1371/journal.pone.0053043,PMC3538747,23308134,CC BY,"The control of infectious diseases such as swine influenza viruses (SwIV) plays an important role in food production both from the animal health and from the public health point of view. Probiotic microorganisms and other health improving food supplements have been given increasing attention in recent years, but, no information on the effects of probiotics on swine influenza virus is available. Here we address this question by assessing the inhibitory potential of the probiotic Enterococcus faecium NCIMB 10415 (E. faecium) on the replication of two porcine strains of influenza virus (H1N1 and H3N2 strain) in a continuous porcine macrophage cell line (3D4/21) and in MDBK cells. Cell cultures were treated with E. faecium at the non-toxic concentration of 1×10(6) CFU/ml in growth medium for 60 to 90 min before, during and after SwIV infection. After further incubation of cultures in probiotic-free growth medium, cell viability and virus propagation were determined at 48 h or 96 h post infection. The results obtained reveal an almost complete recovery of viability of SwIV infected cells and an inhibition of virus multiplication by up to four log units in the E. faecium treated cells. In both 3D4/21- and MDBK-cells a 60 min treatment with E. faecium stimulated nitric oxide (NO) release which is in line with published evidence for an antiviral function of NO. Furthermore, E. faecium caused a modified cellular expression of selected mediators of defence in 3D4-cells: while the expression of TNF-α, TLR-3 and IL-6 were decreased in the SwIV-infected and probiotic treated cells, IL-10 was found to be increased. Since we obtained experimental evidence for the direct adsorptive trapping of SwIV through E. faecium, this probiotic microorganism inhibits influenza viruses by at least two mechanisms, direct physical interaction and strengthening of innate defence at the cellular level.",2013 Jan 7,"['Wang, Zhenya', 'Chai, Weidong', 'Burwinkel, Michael', 'Twardziok, Sven', 'Wrede, Paul', 'Palissa, Christiane', 'Esch, Bettina', 'Schmidt, Michael F. G.']",PLoS One,,,True
7139441855f3ac67f104fb9e067b1359c5582fd6,PMC,The Role of Viral Population Diversity in Adaptation of Bovine Coronavirus to New Host Environments,http://dx.doi.org/10.1371/journal.pone.0052752,PMC3538757,23308119,CC0,"The high mutation rate of RNA viruses enables a diverse genetic population of viral genotypes to exist within a single infected host. In-host genetic diversity could better position the virus population to respond and adapt to a diverse array of selective pressures such as host-switching events. Multiple new coronaviruses, including SARS, have been identified in human samples just within the last ten years, demonstrating the potential of coronaviruses as emergent human pathogens. Deep sequencing was used to characterize genomic changes in coronavirus quasispecies during simulated host-switching. Three bovine nasal samples infected with bovine coronavirus were used to infect human and bovine macrophage and lung cell lines. The virus reproduced relatively well in macrophages, but the lung cell lines were not infected efficiently enough to allow passage of non lab-adapted samples. Approximately 12 kb of the genome was amplified before and after passage and sequenced at average coverages of nearly 950×(454 sequencing) and 38,000×(Illumina). The consensus sequence of many of the passaged samples had a 12 nucleotide insert in the consensus sequence of the spike gene, and multiple point mutations were associated with the presence of the insert. Deep sequencing revealed that the insert was present but very rare in the unpassaged samples and could quickly shift to dominate the population when placed in a different environment. The insert coded for three arginine residues, occurred in a region associated with fusion entry into host cells, and may allow infection of new cell types via heparin sulfate binding. Analysis of the deep sequencing data indicated that two distinct genotypes circulated at different frequency levels in each sample, and support the hypothesis that the mutations present in passaged strains were “selected” from a pre-existing pool rather than through de novo mutation and subsequent population fixation.",2013 Jan 7,"['Borucki, Monica K.', 'Allen, Jonathan E.', 'Chen-Harris, Haiyin', 'Zemla, Adam', 'Vanier, Gilda', 'Mabery, Shalini', 'Torres, Clinton', 'Hullinger, Pamela', 'Slezak, Tom']",PLoS One,,,True
16eb672447620efa83aa59f913d690a95240f488,PMC,The “sweet” side of a long pentraxin: how glycosylation affects PTX3 functions in innate immunity and inflammation,http://dx.doi.org/10.3389/fimmu.2012.00407,PMC3539679,23316195,CC BY,"Innate immunity represents the first line of defense against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs) that recognize pathogen-associated molecular patterns and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a non-redundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the crossroad between innate immunity, inflammation, and female fertility. The human PTX3 protein contains a single N-glycosylation site that is fully occupied by complex type oligosaccharides, mainly fucosylated and sialylated biantennary glycans. Glycosylation has been implicated in a number of PTX3 activities, including neutralization of influenza viruses, modulation of the complement system, and attenuation of leukocyte recruitment. Therefore, this post translational modification might act as a fine tuner of PTX3 functions in native immunity and inflammation. Here we review the studies on PTX3, with emphasis on the glycan-dependent mechanisms underlying pathogen recognition and crosstalk with other components of the innate immune system.",2013 Jan 7,"['Inforzato, Antonio', 'Reading, Patrick C.', 'Barbati, Elisa', 'Bottazzi, Barbara', 'Garlanda, Cecilia', 'Mantovani, Alberto']",Front Immunol,,,True
2d5fdcbc3c2b82ecef0748012b73fc1aa7a2ad96,PMC,A Critical HA1 Neutralizing Domain of H5N1 Influenza in an Optimal Conformation Induces Strong Cross-Protection,http://dx.doi.org/10.1371/journal.pone.0053568,PMC3539987,23320093,CC BY,"The highly pathogenic avian influenza (HPAI) H5N1 viruses, especially the laboratory-generated H5N1 mutants, have demonstrated the potential to cross the species barrier and infect mammals and humans. Consequently, the design of an effective and safe anti-H5N1 vaccine is essential. We previously demonstrated that the full-length hemagglutinin 1 (HA1) could induce significant neutralizing antibody response and protection. Here, we intended to identify the critical neutralizing domain (CND) in an optimal conformation that can elicit strong cross-neutralizing antibodies and protection against divergent H5N1 strains. We thus constructed six recombinant proteins covering different regions of HA1 of A/Anhui/1/2005(H5N1), each of which was fused with foldon (Fd) and Fc of human IgG. We found that the critical fragment fused with Fd/Fc (HA-13–263-Fdc, H5 numbering) that could elicit the strongest neutralizing antibody response is located in the N-terminal region of HA1 (residues 13–263), which covers the receptor-binding domain (RBD, residues 112–263). We then constructed three additional recombinants fused with Fd plus His tag (HA-13–263-Fd-His), Fc only (HA-13–263-Fc), and His tag only (HA-13–263-His), respectively. We found that the HA-13–263-Fdc, which formed an oligomeric conformation, induced the strongest neutralizing antibody response and cross-protection against challenges of two tested H5N1 virus strains covering clade 1: A/VietNam/1194/2004 (VN/1194) or clade 2.3.4: A/Shenzhen/406H/06 (SZ/406H), while HA-13–263-Fc dimer and HA-13–263-Fd-His trimer elicited higher neutralizing antibody response and protection than HA-13–263-His monomer. These results suggest that the oligomeric form of the CND containing the RBD can be further developed as an effective and safe vaccine for cross-protection against divergent strains of H5N1 viruses.",2013 Jan 8,"['Du, Lanying', 'Zhao, Guangyu', 'Sun, Shihui', 'Zhang, Xiujuan', 'Zhou, Xiaojun', 'Guo, Yan', 'Li, Ye', 'Zhou, Yusen', 'Jiang, Shibo']",PLoS One,,,True
2e32842d3ebcee3ffaf4b6822dbac0f41f82130a,PMC,Activation of the Cellular Unfolded Protein Response by Recombinant Adeno-Associated Virus Vectors,http://dx.doi.org/10.1371/journal.pone.0053845,PMC3540029,23320106,CC BY,"The unfolded protein response (UPR) is a stress-induced cyto-protective mechanism elicited towards an influx of large amount of proteins in the endoplasmic reticulum (ER). In the present study, we evaluated if AAV manipulates the UPR pathways during its infection. We first examined the role of the three major UPR axes, namely, endoribonuclease inositol-requiring enzyme-1 (IRE1α), activating transcription factor 6 (ATF6) and PKR-like ER kinase (PERK) in AAV infected cells. Total RNA from mock or AAV infected HeLa cells were used to determine the levels of 8 different ER-stress responsive transcripts from these pathways. We observed a significant up-regulation of IRE1α (up to 11 fold) and PERK (up to 8 fold) genes 12–48 hours after infection with self-complementary (sc)AAV2 but less prominent with single-stranded (ss)AAV2 vectors. Further studies demonstrated that scAAV1 and scAAV6 also induce cellular UPR in vitro, with AAV1 vectors activating the PERK pathway (3 fold) while AAV6 vectors induced a significant increase on all the three major UPR pathways [6–16 fold]. These data suggest that the type and strength of UPR activation is dependent on the viral capsid. We then examined if transient inhibition of UPR pathways by RNA interference has an effect on AAV transduction. siRNA mediated silencing of PERK and IRE1α had a modest effect on AAV2 and AAV6 mediated gene expression (∼1.5–2 fold) in vitro. Furthermore, hepatic gene transfer of scAAV2 vectors in vivo, strongly elevated IRE1α and PERK pathways (2 and 3.5 fold, respectively). However, when animals were pre-treated with a pharmacological UPR inhibitor (metformin) during scAAV2 gene transfer, the UPR signalling and its subsequent inflammatory response was attenuated concomitant to a modest 2.8 fold increase in transgene expression. Collectively, these data suggest that AAV vectors activate the cellular UPR pathways and their selective inhibition may be beneficial during AAV mediated gene transfer.",2013 Jan 8,"['Balakrishnan, Balaji', 'Sen, Dwaipayan', 'Hareendran, Sangeetha', 'Roshini, Vaani', 'David, Sachin', 'Srivastava, Alok', 'Jayandharan, Giridhara R.']",PLoS One,,,True
54125da57282e24d5bcc4c1b60fa54ba1ad784be,PMC,Targeting Herpetic Keratitis by Gene Therapy,http://dx.doi.org/10.1155/2012/594869,PMC3541562,23326647,CC BY,"Ocular gene therapy is rapidly becoming a reality. By November 2012, approximately 28 clinical trials were approved to assess novel gene therapy agents. Viral infections such as herpetic keratitis caused by herpes simplex virus 1 (HSV-1) can cause serious complications that may lead to blindness. Recurrence of the disease is likely and cornea transplantation, therefore, might not be the ideal therapeutic solution. This paper will focus on the current situation of ocular gene therapy research against herpetic keratitis, including the use of viral and nonviral vectors, routes of delivery of therapeutic genes, new techniques, and key research strategies. Whereas the correction of inherited diseases was the initial goal of the field of gene therapy, here we discuss transgene expression, gene replacement, silencing, or clipping. Gene therapy of herpetic keratitis previously reported in the literature is screened emphasizing candidate gene therapy targets. Commonly adopted strategies are discussed to assess the relative advantages of the protective therapy using antiviral drugs and the common gene therapy against long-term HSV-1 ocular infections signs, inflammation and neovascularization. Successful gene therapy can provide innovative physiological and pharmaceutical solutions against herpetic keratitis.",2012 Dec 26,"['Elbadawy, Hossein Mostafa', 'Gailledrat, Marine', 'Desseaux, Carole', 'Ponzin, Diego', 'Ferrari, Stefano']",J Ophthalmol,,,True
b90bc6d84f996cb85c97b94b98f976c7d93367a6,PMC,"Schmallenberg Virus Pathogenesis, Tropism and Interaction with the Innate Immune System of the Host",http://dx.doi.org/10.1371/journal.ppat.1003133,PMC3542112,23326235,CC BY,"Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV.",2013 Jan 10,"['Varela, Mariana', 'Schnettler, Esther', 'Caporale, Marco', 'Murgia, Claudio', 'Barry, Gerald', 'McFarlane, Melanie', 'McGregor, Eva', 'Piras, Ilaria M.', 'Shaw, Andrew', 'Lamm, Catherine', 'Janowicz, Anna', 'Beer, Martin', 'Glass, Mandy', 'Herder, Vanessa', 'Hahn, Kerstin', 'Baumgärtner, Wolfgang', 'Kohl, Alain', 'Palmarini, Massimo']",PLoS Pathog,,,True
bb7718e2a9a390578e8d3f5ea081f08d3fd17185,PMC,Viral and Bacterial Interactions in the Upper Respiratory Tract,http://dx.doi.org/10.1371/journal.ppat.1003057,PMC3542149,23326226,CC BY,"Respiratory infectious diseases are mainly caused by viruses or bacteria that often interact with one another. Although their presence is a prerequisite for subsequent infections, viruses and bacteria may be present in the nasopharynx without causing any respiratory symptoms. The upper respiratory tract hosts a vast range of commensals and potential pathogenic bacteria, which form a complex microbial community. This community is assumed to be constantly subject to synergistic and competitive interspecies interactions. Disturbances in the equilibrium, for instance due to the acquisition of new bacteria or viruses, may lead to overgrowth and invasion. A better understanding of the dynamics between commensals and pathogens in the upper respiratory tract may provide better insight into the pathogenesis of respiratory diseases. Here we review the current knowledge regarding specific bacterial–bacterial and viral–bacterial interactions that occur in the upper respiratory niche, and discuss mechanisms by which these interactions might be mediated. Finally, we propose a theoretical model to summarize and illustrate these mechanisms.",2013 Jan 10,"['Bosch, Astrid A. T. M.', 'Biesbroek, Giske', 'Trzcinski, Krzysztof', 'Sanders, Elisabeth A. M.', 'Bogaert, Debby']",PLoS Pathog,,,True
360e2ae0c8c522d48cb5414c1e982d96e40165b6,PMC,A Monoclonal Antibody-Based Copro-ELISA Kit for Canine Echinococcosis to Support the PAHO Effort for Hydatid Disease Control in South America,http://dx.doi.org/10.1371/journal.pntd.0001967,PMC3542170,23326610,CC BY,"Cystic echinococcosis is still a major concern in South America. While some regions show advances in the control of the disease, others have among the highest incidence in the world. To reverse this situation the Pan American Health Organization (PAHO) has launched a regional project on cystic echinococcosis control and surveillance. An early concern of the program was the lack of a standardized diagnostic tool to monitor infection in dogs, a key target of control programs. Under this premise, we have developed a new copro-ELISA test after extensive screening of a large panel of monoclonal antibodies (MAbs) and polyclonal sera, which performs with high standards of sensitivity (92.6%) and specificity (86.4%) as established by necropsy diagnosis of dogs. The key component of the test, MAbEg9 has a convenient IgG isotype and reacts with a periodate-resistant epitope found in high molecular weight components of the worm. Time-course analysis of experimentally infected dogs showed that even animals with a very low number of parasites could be detected as early as day 20 post infection. The test was formulated in a ready-to-use kit format with proven stability of each component for a minimum of 3 months at room temperature. This characteristic facilitates its standardized use and shipping to other laboratories, which was demonstrated by the identical results obtained by two different laboratories in Peru and our own laboratory when a large number of field samples were analyzed independently in a blind fashion.",2013 Jan 10,"['Morel, Noelia', 'Lassabe, Gabriel', 'Elola, Susana', 'Bondad, Mauricio', 'Herrera, Silvia', 'Marí, Carlos', 'Last, Jerold A.', 'Jensen, Oscar', 'Gonzalez-Sapienza, Gualberto']",PLoS Negl Trop Dis,,,True
0d673eba8d23c47646d0f5b69937ee87716aa1df,PMC,Co-circulation of diverse paramyxoviruses in an urban African fruit bat population,http://dx.doi.org/10.1099/vir.0.039339-0,PMC3542712,22205718,CC BY,"Bats constitute a reservoir of zoonotic infections and some bat paramyxoviruses are capable of cross-species transmission, often with fatal consequences. Determining the level of viral diversity in reservoir populations is fundamental to understanding and predicting viral emergence. This is particularly relevant for RNA viruses where the adaptive mutations required for cross-species transmission can be present in the reservoir host. We report the use of non-invasively collected, pooled, neat urine samples as a robust sample type for investigating paramyxoviruses in bat populations. Using consensus PCR assays we have detected a high incidence and genetic diversity of novel paramyxoviruses in an urban fruit bat population over a short period of time. This may suggest a similarly unique relationship between bats and the members of the family Paramyxoviridae as proposed for some other viral families. Additionally, the high rate of bat–human contact at the study site calls for the zoonotic potential of the detected viruses to be investigated further.",2012 Apr,"['Baker, K. S.', 'Todd, S.', 'Marsh, G.', 'Fernandez-Loras, A.', 'Suu-Ire, R.', 'Wood, J. L. N.', 'Wang, L. F.', 'Murcia, P. R.', 'Cunningham, A. A.']",J Gen Virol,,,True
5afa333a59a3d818c758dbc752463b90436a1c57,PMC,ISG56/IFIT1 is primarily responsible for interferon-induced changes to patterns of parainfluenza virus type 5 transcription and protein synthesis,http://dx.doi.org/10.1099/vir.0.046797-0,PMC3542720,23052390,CC BY,"Interferon (IFN) induces an antiviral state in cells that results in alterations of the patterns and levels of parainfluenza virus type 5 (PIV5) transcripts and proteins. This study reports that IFN-stimulated gene 56/IFN-induced protein with tetratricopeptide repeats 1 (ISG56/IFIT1) is primarily responsible for these effects of IFN. It was shown that treating cells with IFN after infection resulted in an increase in virus transcription but an overall decrease in virus protein synthesis. As there was no obvious decrease in the overall levels of cellular protein synthesis in infected cells treated with IFN, these results suggested that ISG56/IFIT1 selectively inhibits the translation of viral mRNAs. This conclusion was supported by in vitro translation studies. Previous work has shown that ISG56/IFIT1 can restrict the replication of viruses lacking a 2′-O-methyltransferase activity, an enzyme that methylates the 2′-hydroxyl group of ribose sugars in the 5′-cap structures of mRNA. However, the data in the current study strongly suggested that PIV5 mRNAs are methylated at the 2′-hydroxyl group and thus that ISG56/IFIT1 selectively inhibits the translation of PIV5 mRNA by some as yet unrecognized mechanism. It was also shown that ISG56/IFIT1 is primarily responsible for the IFN-induced inhibition of PIV5.",2013 Jan,"['Andrejeva, J.', 'Norsted, H.', 'Habjan, M.', 'Thiel, V.', 'Goodbourn, S.', 'Randall, R. E.']",J Gen Virol,,,True
f5bdf18567bb3760e1ce05008135f0270badbd5c,PMC,Pre-existing immunity against vaccine vectors – friend or foe?,http://dx.doi.org/10.1099/mic.0.049601-0,PMC3542731,23175507,CC BY,"Over the last century, the successful attenuation of multiple bacterial and viral pathogens has led to an effective, robust and safe form of vaccination. Recently, these vaccines have been evaluated as delivery vectors for heterologous antigens, as a means of simultaneous vaccination against two pathogens. The general consensus from published studies is that these vaccine vectors have the potential to be both safe and efficacious. However, some of the commonly employed vectors, for example Salmonella and adenovirus, often have pre-existing immune responses in the host and this has the potential to modify the subsequent immune response to a vectored antigen. This review examines the literature on this topic, and concludes that for bacterial vectors there can in fact, in some cases, be an enhancement in immunogenicity, typically humoral, while for viral vectors pre-existing immunity is a hindrance for subsequent induction of cell-mediated responses.",2013 Jan,"['Saxena, Manvendra', 'Van, Thi Thu Hao', 'Baird, Fiona J.', 'Coloe, Peter J.', 'Smooker, Peter M.']",Microbiology,,,True
f4a7339511490ed2b84a8b9189b5f2f05ff57082,PMC,Non-canonical translation in RNA viruses,http://dx.doi.org/10.1099/vir.0.042499-0,PMC3542737,22535777,CC BY,"Viral protein synthesis is completely dependent upon the translational machinery of the host cell. However, many RNA virus transcripts have marked structural differences from cellular mRNAs that preclude canonical translation initiation, such as the absence of a 5′ cap structure or the presence of highly structured 5′UTRs containing replication and/or packaging signals. Furthermore, whilst the great majority of cellular mRNAs are apparently monocistronic, RNA viruses must often express multiple proteins from their mRNAs. In addition, RNA viruses have very compact genomes and are under intense selective pressure to optimize usage of the available sequence space. Together, these features have driven the evolution of a plethora of non-canonical translational mechanisms in RNA viruses that help them to meet these challenges. Here, we review the mechanisms utilized by RNA viruses of eukaryotes, focusing on internal ribosome entry, leaky scanning, non-AUG initiation, ribosome shunting, reinitiation, ribosomal frameshifting and stop-codon readthrough. The review will highlight recently discovered examples of unusual translational strategies, besides revisiting some classical cases.",2012 Jul,"['Firth, Andrew E.', 'Brierley, Ian']",J Gen Virol,,,True
0043d044273b8eb1585d3a66061e9b4e03edc062,PMC,"Evaluation of the tuberculosis programme in Ningxia Hui Autonomous region, the People’s Republic of China: a retrospective case study",http://dx.doi.org/10.1186/1471-2458-12-1110,PMC3543161,23259484,CC BY,"BACKGROUND: Tuberculosis is a devastating disease due to its rapid transmission and high rate of mortality. Ningxia Hui Autonomous Region (NHAR), located in the North-west, is one of the poorest provinces in China and national surveys have shown TB has been hyper endemic in NHAR for several decades. As no active surveys had been undertaken since the initiation of the DOTS control program across all of NHAR. METHODS: A retrospective study was undertaken of all clinical records of TB patients registered from January 2005 to September 2009. Poisson regression was performed to investigate the change in incidence over time and accounted for age, sex and county. Length of time on treatment, disease severity and patient delay were assessed by county. RESULTS: More than 30% of patients had been on treatment for over 12 months and 10% for over 3 years, reflecting drug-resistance or failure of DOTS. More than 93% of patients had grade III disease at time of diagnosis and >15% of patients had severe disease grade IV-V in some NHAR counties. Further, 8.8% of patients were not diagnosed for over 6 months from the onset of symptoms; this was as high as 20% in some counties. The reported incidence of TB is most likely grossly underestimated and the data indicate TB is a major public health concern in NHAR. CONCLUSIONS: It is clear that active surveillance is necessary to determine the full extent of the burden of TB in NHAR. New control and treatment strategies for TB are required that increase awareness in the health-care system and at the individual and community level.",2012 Dec 23,"['Yang, Yu Rong', 'McManus, Donald P', 'Gray, Darren J', 'Wang, Xiao Ling', 'Yang, Shu Kun', 'Ross, Allen G', 'Williams, Gail M', 'Ellis, Magda K']",BMC Public Health,,,True
5a69605f00c8bcbe367fe3eeeefa835438f4b955,PMC,"Treatment of Common Cold Patients with the Shi-Cha Capsule: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Dose-Escalation Trial",http://dx.doi.org/10.1155/2012/254571,PMC3544370,23346193,CC BY,"This study was designed to determine the therapeutic efficacy and safety of the Shi-cha capsule, a Chinese herbal formula, in the treatment of patients with wind-cold type common cold. In our multi-center, prospective, double-blind, randomized, placebo-controlled, dose-escalation trial, patients with wind-cold type common cold received 0.6 g of Shi-cha capsule plus 0.6 g placebo (group A), 1.2 g of Shi-cha capsule (group B), or 1.2 g placebo (group C), three times daily for 3 days and followed up to 10 days. The primary end point was all symptom duration. The secondary end points were main symptom duration, minor symptom duration, the changes in cumulative symptom score, main symptom score, and minor symptom score 4 days after the treatment, as well as adverse events. A total of 377 patients were recruited and 360 met the inclusive criteria; 120 patients constituted each treatment group. Compared with patients in group C, patients in groups A and B had significant improvement in the all symptom duration, main symptom duration, minor symptom duration, as well as change from baseline of cumulative symptom score, main symptom score, and minor symptom score at day 4. The symptom durations and scores showed slight superiority of group B over group A, although these differences were not statistically significant. There were no differences in adverse events. The Shi-cha capsule is efficacious and safe for the treatment of patients with wind-cold type common cold. Larger trials are required to fully assess the benefits and safety of this treatment for common cold.",2012 Dec 27,"['Chang, Jing', 'Dong, Shou-Jin', 'She, Bin', 'Zhang, Rui-Ming', 'Meng, Mao-Bin', 'Xu, Yan-Ling', 'Wan, Li-Ling', 'Shi, Ke-Hua', 'Pan, Jun-Hun', 'Mao, Bing']",Evid Based Complement Alternat Med,,,False
ec64f7f7ece2c16fb0a4210295b2527714b11ee0,PMC,"Treatment of Common Cold Patients with the Shi-Cha Capsule: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Dose-Escalation Trial",http://dx.doi.org/10.1155/2012/254571,PMC3544370,23346193,CC BY,"This study was designed to determine the therapeutic efficacy and safety of the Shi-cha capsule, a Chinese herbal formula, in the treatment of patients with wind-cold type common cold. In our multi-center, prospective, double-blind, randomized, placebo-controlled, dose-escalation trial, patients with wind-cold type common cold received 0.6 g of Shi-cha capsule plus 0.6 g placebo (group A), 1.2 g of Shi-cha capsule (group B), or 1.2 g placebo (group C), three times daily for 3 days and followed up to 10 days. The primary end point was all symptom duration. The secondary end points were main symptom duration, minor symptom duration, the changes in cumulative symptom score, main symptom score, and minor symptom score 4 days after the treatment, as well as adverse events. A total of 377 patients were recruited and 360 met the inclusive criteria; 120 patients constituted each treatment group. Compared with patients in group C, patients in groups A and B had significant improvement in the all symptom duration, main symptom duration, minor symptom duration, as well as change from baseline of cumulative symptom score, main symptom score, and minor symptom score at day 4. The symptom durations and scores showed slight superiority of group B over group A, although these differences were not statistically significant. There were no differences in adverse events. The Shi-cha capsule is efficacious and safe for the treatment of patients with wind-cold type common cold. Larger trials are required to fully assess the benefits and safety of this treatment for common cold.",2012 Dec 27,"['Chang, Jing', 'Dong, Shou-Jin', 'She, Bin', 'Zhang, Rui-Ming', 'Meng, Mao-Bin', 'Xu, Yan-Ling', 'Wan, Li-Ling', 'Shi, Ke-Hua', 'Pan, Jun-Hun', 'Mao, Bing']",Evid Based Complement Alternat Med,,,True
1008bb267f9b05fcec7b715eab47f4a5c659c7dd,PMC,Teacher led school-based surveillance can allow accurate tracking of emerging infectious diseases - evidence from serial cross-sectional surveys of febrile respiratory illness during the H1N1 2009 influenza pandemic in Singapore,http://dx.doi.org/10.1186/1471-2334-12-336,PMC3544582,23206689,CC BY,"BACKGROUND: Schools are important foci of influenza transmission and potential targets for surveillance and interventions. We compared several school-based influenza monitoring systems with clinic-based influenza-like illness (ILI) surveillance, and assessed the variation in illness rates between and within schools. METHODS: During the initial wave of pandemic H1N1 (pdmH1N1) infections from June to Sept 2009 in Singapore, we collected data on nation-wide laboratory confirmed cases (Sch-LCC) and daily temperature monitoring (Sch-DTM), and teacher-led febrile respiratory illness reporting in 6 sentinel schools (Sch-FRI). Comparisons were made against age-stratified clinic-based influenza-like illness (ILI) data from 23 primary care clinics (GP-ILI) and proportions of ILI testing positive for pdmH1N1 (Lab-ILI) by computing the fraction of cumulative incidence occurring by epidemiological week 30 (when GP-ILI incidence peaked); and cumulative incidence rates between school-based indicators and sero-epidemiological pdmH1N1 incidence (estimated from changes in prevalence of A/California/7/2009 H1N1 hemagglutination inhibition titers ≥ 40 between pre-epidemic and post-epidemic sera). Variation in Sch-FRI rates in the 6 schools was also investigated through a Bayesian hierarchical model. RESULTS: By week 30, for primary and secondary school children respectively, 63% and 79% of incidence for Sch-LCC had occurred, compared with 50% and 52% for GP-ILI data, and 48% and 53% for Sch-FRI. There were 1,187 notified cases and 7,588 episodes in the Sch-LCC and Sch-DTM systems; given school enrollment of 485,723 children, this represented 0.24 cases and 1.6 episodes per 100 children respectively. Mean Sch-FRI rate was 28.8 per 100 children (95% CI: 27.7 to 29.9) in the 6 schools. We estimate from serology that 41.8% (95% CI: 30.2% to 55.9%) of primary and 43.2% (95% CI: 28.2% to 60.8%) of secondary school-aged children were infected. Sch-FRI rates were similar across the 6 schools (23 to 34 episodes per 100 children), but there was widespread variation by classrooms; in the hierarchical model, omitting age and school effects was inconsequential but neglecting classroom level effects led to highly significant reductions in goodness of fit. CONCLUSIONS: Epidemic curves from Sch-FRI were comparable to GP-ILI data, and Sch-FRI detected substantially more infections than Sch-LCC and Sch-DTM. Variability in classroom attack rates suggests localized class-room transmission.",2012 Dec 4,"['Chen, Mark IC', 'Chong, Chia Yin']",BMC Infect Dis,,,True
04c1c40f4464bc035e57d0ecf2f8a033e4e7f466,PMC,"Acute care utilization due to hospitalizations for pediatric lower respiratory tract infections in British Columbia, Canada",http://dx.doi.org/10.1186/1472-6963-12-451,PMC3544629,23217103,CC BY,"BACKGROUND: Pediatric LRTI hospitalizations are a significant burden on patients, families, and healthcare systems. This study determined the burden of pediatric LRTIs on hospital settings in British Columbia and the benefits of prevention strategies as they relate to healthcare resource demand. METHODS: LRTI inpatient episodes for patients <19 years of age during 2008–2010 were extracted from the BC Discharge Abstract Database. The annual number of acute care beds required to treat pediatric LRTIs was estimated. Sub-analyses determined the burden due to infants <1 year of age and high-risk infants. Population projections were used to forecast LRTI hospitalizations and the effectiveness of public health initiatives to reduce the incidence of LRTIs to 2020 and 2030. RESULTS: During 2008–2010, LRTI as the primary diagnosis accounted for 32.0 and 75.9% hospitalizations for diseases of the respiratory system in children <19 years of age and infants <1 year of age, respectively. Infants <1 year of age accounted for 47 and 77% hospitalizations due to pediatric LRTIs and pediatric LRTI hospitalizations specifically due to respiratory syncytial virus (RSV), respectively. The average length of stay was 3.1 days for otherwise healthy infants <1 year of age and 9.1 days for high-risk infants (P <0.0001). 73.1% pediatric LRTI hospitalizations occurred between November and April. Over the study timeframe, 19.6 acute care beds were required on average to care for pediatric LRTIs which increased to 64.0 beds at the peak of LRTI hospitalizations. Increases in LRTI bed-days of 5.5 and 16.2% among <19 year olds by 2020 and 2030, respectively, were predicted. Implementation of appropriate prevention strategies could cause 307 and 338 less LRTI hospitalizations in <19 year olds in 2020 and 2030, respectively. CONCLUSION: Pediatric LRTI hospitalizations require significant use of acute care infrastructure particularly between November and April. Population projections show the burden may increase in the next 20 years, but implementation of effective public health prevention strategies may contribute to reducing the acute care demand and to supporting efforts for overall pediatric healthcare sustainability.",2012 Dec 8,"['Santibanez, Pablo', 'Gooch, Katherine', 'Vo, Pamela', 'Lorimer, Michelle', 'Sandino, Yurik']",BMC Health Serv Res,,,True
a3d1def9eb134591e3d0b38dc1c1330745da34a0,PMC,Comparison of the geographical distribution of feline immunodeficiency virus and feline leukemia virus infections in the United States of America (2000–2011),http://dx.doi.org/10.1186/1746-6148-9-2,PMC3544736,23289366,CC BY,"BACKGROUND: Although feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) have similar risk factors and control measures, infection rates have been speculated to vary in geographic distribution over North America. Since both infections are endemic in North America, it was assumed as a working hypothesis that their geographic distributions were similar. Hence, the purpose of this exploratory analysis was to investigate the comparative geographical distribution of both viral infections. Counts of FIV (n=17,108) and FeLV (n=30,017) positive serology results (FIV antibody and FeLV ELISA) were obtained for 48 contiguous states and District of Columbia of the United States of America (US) from the IDEXX Laboratories website. The proportional morbidity ratio of FIV to FeLV infection was estimated for each administrative region and its geographic distribution pattern was visualized by a choropleth map. Statistical evidence of an excess in the proportional morbidity ratio from unity was assessed using the spatial scan test under the normal probability model. RESULTS: This study revealed distinct spatial distribution patterns in the proportional morbidity ratio suggesting the presence of one or more relevant and geographically varying risk factors. The disease map indicates that there is a higher prevalence of FIV infections in the southern and eastern US compared to FeLV. In contrast, FeLV infections were observed to be more frequent in the western US compared to FIV. The respective excess in proportional morbidity ratio was significant with respect to the spatial scan test (p < 0.05). CONCLUSIONS: The observed variability in the geographical distribution of the proportional morbidity ratio of FIV to FeLV may be related to the presence of an additional or unique, but yet unknown, spatial risk factor. Putative factors may be geographic variations in specific virus strains and rate of vaccination. Knowledge of these factors and the geographical distributions of these infections can inform recommendations for testing, management and prevention. However, further studies are required to investigate the potential association of these factors with FIV and FeLV.",2013 Jan 5,"['Chhetri, Bimal K', 'Berke, Olaf', 'Pearl, David L', 'Bienzle, Dorothee']",BMC Vet Res,,,True
59a11e8976b666ba112da942d7ba7c698d06a9e8,PMC,Mutations in the Fusion Protein Cleavage Site of Avian Paramyxovirus Serotype 4 Confer Increased Replication and Syncytium Formation In Vitro but Not Increased Replication and Pathogenicity in Chickens and Ducks,http://dx.doi.org/10.1371/journal.pone.0050598,PMC3544850,23341874,CC0,"To evaluate the role of the F protein cleavage site in the replication and pathogenicity of avian paramyxoviruses (APMVs), we constructed a reverse genetics system for recovery of infectious recombinant APMV-4 from cloned cDNA. The recovered recombinant APMV-4 resembled the biological virus in growth characteristics in vitro and in pathogenicity in vivo. The F cleavage site sequence of APMV-4 (DIQPR↓F) contains a single basic amino acid, at the -1 position. Six mutant APMV-4 viruses were recovered in which the F protein cleavage site was mutated to contain increased numbers of basic amino acids or to mimic the naturally occurring cleavage sites of several paramyxoviruses, including neurovirulent and avirulent strains of NDV. The presence of a glutamine residue at the -3 position was found to be important for mutant virus recovery. In addition, cleavage sites containing the furin protease motif conferred increased replication and syncytium formation in vitro. However, analysis of viral pathogenicity in 9-day-old embryonated chicken eggs, 1-day-old and 2-week-old chickens, and 3-week-old ducks showed that none the F protein cleavage site mutations altered the replication, tropism, and pathogenicity of APMV-4, and no significant differences were observed among the parental and mutant APMV-4 viruses in vivo. Although parental and mutant viruses replicated somewhat better in ducks than in chickens, they all were highly restricted and avirulent in both species. These results suggested that the cleavage site sequence of the F protein is not a limiting determinant of APMV-4 pathogenicity in chickens and ducks.",2013 Jan 14,"['Kim, Shin-Hee', 'Xiao, Sa', 'Shive, Heather', 'Collins, Peter L.', 'Samal, Siba K.']",PLoS One,,,True
fdd06eeb020a963754fee36852a5918a93f7856d,PMC,"Initial Antihypertensive Prescription and Switching: A 5 Year Cohort Study from 250,851 Patients",http://dx.doi.org/10.1371/journal.pone.0053625,PMC3544913,23341959,CC BY,"PURPOSE: Adverse effects of antihypertensive therapy incur substantial cost. We evaluated whether any major classes of antihypertensive drugs were significantly associated with switching as a proxy measure of medication side effects in a large Chinese population in Hong Kong. METHODS: From a clinical database, all adult patients newly prescribed an antihypertensive mono-therapy in Hong Kong between the years 2001–2003 and 2005 were included. Those who paid only one visit, died or stayed in the cohort for <180 days after the prescription, or prescribed more than one antihypertensive agent were excluded. The factors associated with switching at 180 days were evaluated by multivariate regression analyses. Age, gender, payment status, service type, district of residence, drug class, systolic and diastolic blood pressure levels were predictor variables. RESULTS: From 250,851 subjects, 159,813 patients were eligible. A total of 6,163 (3.9%) switched their medications within 180 days. Patients prescribed thiazide diuretics had the highest switching rate (5.6%), followed by ACEIs (4.5%), CCBs (4.4%) and beta-blockers (3.2%). When compared with ACEIs, patients on thiazide diuretics were significantly more likely to be switchers (adjusted odds ratio [AOR] 1.49, 95% C.I. 1.31–1.69, p<0.001), whilst patients prescribed CCBs and beta-blockers were similarly likely to have switching. Following these patients up for 5 years showed that thiazide had the most marked increase in switching rate. CONCLUSIONS: The higher rates of switching among thiazide diuretics in this study might raise a probably greater incidence of their adverse effects in this Chinese population, yet other factors might also influence switching rates. Patients prescribed thiazide diuretics for longer term should be observed for their intolerability.",2013 Jan 14,"['Wong, Martin C. S.', 'Tam, Wilson W. S.', 'Cheung, Clement S. K.', 'Tong, Ellen L. H.', 'Sek, Antonio C. H.', 'John, George', 'Cheung, N. T.', 'Yan, Bryan P. Y.', 'Yu, C. M.', 'Leeder, Stephen', 'Griffiths, Sian']",PLoS One,,,True
c59d6e789176b928523129adb96ca495720a3b4a,PMC,Enhanced CD8 T-cell anti-viral function and clinical disease in B7-H1-deficient mice requires CD4 T cells during encephalomyelitis,http://dx.doi.org/10.1186/1742-2094-9-269,PMC3545890,23237504,CC BY,"BACKGROUND: Anti-viral CD8 T-cell activity is enhanced and prolonged by CD4 T-cell-mediated help, but negatively regulated by inhibitory B7-H1 interactions. During viral encephalomyelitis, the absence of CD4 T cells decreases CD8 T cell activity and impedes viral control in the central nervous system (CNS). By contrast, the absence of B7-H1 enhances CD8 T-cell function and accelerates viral control, but increases morbidity. However, the relative contribution of CD4 T cells to CD8 function in the CNS, in the absence of B7-H1, remains unclear. METHODS: Wild-type (WT) and B7-H1(−/−) mice were infected with a gliatropic coronavirus and CD4 T cells depleted to specifically block T helper function in the CNS. Flow cytometry and gene expression analysis of purified T-cell populations from lymph nodes and the CNS was used to directly monitor ex vivo T-cell effector function. The biological affects of altered T-cell responses were evaluated by analysis of viral control and spinal-cord pathology. RESULTS: Increased anti-viral activity by CD8 T cells in the CNS of B7-H1(−/−) mice was lost upon depletion of CD4 T cells; however, despite concomitant loss of viral control, the clinical disease was less severe. CD4 depletion in B7-H1(−/−) mice also decreased inducible nitric oxide synthase expression by microglia and macrophages, consistent with decreased microglia/macrophage activation and reduced interferon (IFN)-γ. Enhanced production of IFN-γ, interleukin (IL)-10 and IL-21 mRNA was seen in CD4 T cells from infected B7-H1(−/−) compared with WT mice, suggesting that over-activated CD4 T cells primarily contribute to the increased pathology. CONCLUSIONS: The local requirement of CD4 T-cell help for CD8 T-cell function is not overcome if B7-H1 inhibitory signals are lost. Moreover, the increased effector activity by CD8 T cells in the CNS of B7-H1(−/−) mice is attributable not only to the absence of B7-H1 upregulation on major histocompatibility complex class I-presenting resident target cells, but also to enhanced local CD4 T-cell function. B7-H1-mediated restraint of CD4 T-cell activity is thus crucial to dampen both CD8 T-cell function and microglia/macrophage activation, thereby providing protection from T-cell-mediated bystander damage.",2012 Dec 14,"['Phares, Timothy W', 'Stohlman, Stephen A', 'Hinton, David R', 'Bergmann, Cornelia C']",J Neuroinflammation,,,True
3acc047295ee11b02f13aac787a12fe114d58558,PMC,Identification of a novel Getah virus by Virus-Discovery-cDNA random amplified polymorphic DNA (RAPD),http://dx.doi.org/10.1186/1471-2180-12-305,PMC3547691,23268691,CC BY,"BACKGROUND: The identification of new virus strains is important for the study of infectious disease, but current (or existing) molecular biology methods are limited since the target sequence must be known to design genome-specific PCR primers. Thus, we developed a new method for the discovery of unknown viruses based on the cDNA - random amplified polymorphic DNA (cDNA-RAPD) technique. Getah virus, belonging to the family Togaviridae in the genus Alphavirus, is a mosquito-borne enveloped RNA virus that was identified using the Virus-Discovery-cDNA RAPD (VIDISCR) method. RESULTS: A novel Getah virus was identified by VIDISCR from suckling mice exposed to mosquitoes (Aedes albopictus) collected in Yunnan Province, China. The non-structural protein gene, nsP3, the structural protein gene, the capsid protein gene, and the 3'-untranslated region (UTR) of the novel Getah virus isolate were cloned and sequenced. Nucleotide sequence identities of each gene were determined to be 97.1–99.3%, 94.9–99.4%, and 93.6–99.9%, respectively, when compared with the genomes of 10 other representative strains of Getah virus. CONCLUSIONS: The VIDISCR method was able to identify known virus isolates and a novel isolate of Getah virus from infected mice. Phylogenetic analysis indicated that the YN08 isolate was more closely related to the Hebei HB0234 strain than the YN0540 strain, and more genetically distinct from the MM2021 Malaysia primitive strain.",2012 Dec 27,"['Hu, Tingsong', 'Zheng, Ying', 'Zhang, Yan', 'Li, Gangshan', 'Qiu, Wei', 'Yu, Jing', 'Cui, Qinghua', 'Wang, Yiyin', 'Zhang, Chaoxiong', 'Zhou, Xiaofang', 'Feng, Ziliang', 'Zhou, Weiguo', 'Fan, Quanshui', 'Zhang, Fuqiang']",BMC Microbiol,,,True
29da5f5d00af5c47f9b3a0a49d561f8caffb0cf3,PMC,Anti-rotaviral effects of Glycyrrhiza uralensis extract in piglets with rotavirus diarrhea,http://dx.doi.org/10.1186/1743-422X-9-310,PMC3547719,23244491,CC BY,"BACKGROUND: Since rotavirus is one of the leading pathogens that cause severe gastroenteritis and represents a serious threat to human and animal health, researchers have been searching for cheap, safe, and effective anti-rotaviral drugs. There is a widespread of interest in using natural products as antiviral agents, and among them, licorice derived from Glycyrrhiza spp. has exerted antiviral properties against several viruses. In this study, anti-rotaviral efficacy of Glycyrrhiza uralensis extract (GUE) as an effective and cheaper remedy without side-effects was evaluated in colostrums-deprived piglets after induction of rotavirus diarrhea. METHODS: Colostrums-deprived piglets were inoculated with porcine rotavirus K85 (G5P[7]) strain. On the onset of diarrhea, piglets were treated with different concentration of GUE. To evaluate the antiviral efficacy of GUE, fecal consistency score, fecal virus shedding and histological changes of the small intestine, mRNA expression levels of inflammation-related cytokines (IL8, IL10, IFN-β, IFN-γ and TNF-α), signaling molecules (p38 and JNK), and transcription factor (NFκB) in the small intestine and spleen were determined. RESULTS: Among the dosages (100-400 mg/ml) administrated to animals, 400 mg/ml of GUE cured diarrhea, and markedly improved small intestinal lesion score and fecal virus shedding. mRNA expression levels of inflammation-related cytokines (IL8, IL10, IFN-β, IFN-γ and TNF-α), signaling molecules (p38 and JNK), and transcription factor (NFκB) in the small intestine and spleen were markedly increased in animals with RVA-induced diarrhea, but dose- dependently decreased in GUE treated animals after RVA-induced diarrhea. CONCLUSIONS: GUE cures rotaviral enteritis by coordinating antiviral and anti-inflammatory effects. Therapy of this herbal medicine can be a viable medication for curing rotaviral enteritis in animals and humans.",2012 Dec 18,"['Alfajaro, Mia Madel', 'Kim, Hyun-Jeong', 'Park, Jun-Gyu', 'Ryu, Eun-Hye', 'Kim, Ji-Yun', 'Jeong, Young-Ju', 'Kim, Deok-Song', 'Hosmillo, Myra', 'Son, Kyu-Yeol', 'Lee, Ju-Hwan', 'Kwon, Hyung-Jun', 'Ryu, Young Bae', 'Park, Su-Jin', 'Park, Sang-Ik', 'Lee, Woo Song', 'Cho, Kyoung-Oh']",Virol J,,,True
a0d73d877a6bcede67ac884d7e5ada5dd3eb810c,PMC,The Immunosuppressive Agent Mizoribine Monophosphate Is an Inhibitor of the Human RNA Capping Enzyme,http://dx.doi.org/10.1371/journal.pone.0054621,PMC3547949,23349942,CC BY,"Mizoribine monophosphate (MZP) is a specific inhibitor of the cellular inosine-5′-monophosphate dehydrogenase (IMPDH), the enzyme catalyzing the rate-limiting step of de novo guanine nucleotide biosynthesis. MZP is a highly potent antagonistic inhibitor of IMPDH that blocks the proliferation of T and B lymphocytes that use the de novo pathway of guanine nucleotide synthesis almost exclusively. In the present study, we investigated the ability of MZP to directly inhibit the human RNA capping enzyme (HCE), a protein harboring both RNA 5′-triphosphatase and RNA guanylyltransferase activities. HCE is involved in the synthesis of the cap structure found at the 5′ end of eukaryotic mRNAs, which is critical for the splicing of the cap-proximal intron, the transport of mRNAs from the nucleus to the cytoplasm, and for both the stability and translation of mRNAs. Our biochemical studies provide the first insight that MZP can inhibit the formation of the RNA cap structure catalyzed by HCE. In the presence of MZP, the RNA 5′-triphosphatase activity appears to be relatively unaffected while the RNA guanylyltransferase activity is inhibited, indicating that the RNA guanylyltransferase activity is the main target of MZP inhibition. Kinetic studies reveal that MZP is a non-competitive inhibitor that likely targets an allosteric site on HCE. Mizoribine also impairs mRNA capping in living cells, which could account for the global mechanism of action of this therapeutic agent. Together, our study clearly demonstrates that mizoribine monophosphate inhibits the human RNA guanylyltransferase in vitro and impair mRNA capping in cellulo.",2013 Jan 17,"['Picard-Jean, Frédéric', 'Bougie, Isabelle', 'Shuto, Satoshi', 'Bisaillon, Martin']",PLoS One,,,True
6ed77e5ebba3c0f0b10c6e0af3e8df28b57335e6,PMC,Automated degenerate PCR primer design for high-throughput sequencing improves efficiency of viral sequencing,http://dx.doi.org/10.1186/1743-422X-9-261,PMC3548747,23131097,CC BY,"BACKGROUND: In a high-throughput environment, to PCR amplify and sequence a large set of viral isolates from populations that are potentially heterogeneous and continuously evolving, the use of degenerate PCR primers is an important strategy. Degenerate primers allow for the PCR amplification of a wider range of viral isolates with only one set of pre-mixed primers, thus increasing amplification success rates and minimizing the necessity for genome finishing activities. To successfully select a large set of degenerate PCR primers necessary to tile across an entire viral genome and maximize their success, this process is best performed computationally. RESULTS: We have developed a fully automated degenerate PCR primer design system that plays a key role in the J. Craig Venter Institute’s (JCVI) high-throughput viral sequencing pipeline. A consensus viral genome, or a set of consensus segment sequences in the case of a segmented virus, is specified using IUPAC ambiguity codes in the consensus template sequence to represent the allelic diversity of the target population. PCR primer pairs are then selected computationally to produce a minimal amplicon set capable of tiling across the full length of the specified target region. As part of the tiling process, primer pairs are computationally screened to meet the criteria for successful PCR with one of two described amplification protocols. The actual sequencing success rates for designed primers for measles virus, mumps virus, human parainfluenza virus 1 and 3, human respiratory syncytial virus A and B and human metapneumovirus are described, where >90% of designed primer pairs were able to consistently successfully amplify >75% of the isolates. CONCLUSIONS: Augmenting our previously developed and published JCVI Primer Design Pipeline, we achieved similarly high sequencing success rates with only minor software modifications. The recommended methodology for the construction of the consensus sequence that encapsulates the allelic variation of the targeted population and is a key step prior to designing degenerate primers is also formally described.",2012 Nov 6,"['Li, Kelvin', 'Shrivastava, Susmita', 'Brownley, Anushka', 'Katzel, Dan', 'Bera, Jayati', 'Nguyen, Anh Thu', 'Thovarai, Vishal', 'Halpin, Rebecca', 'Stockwell, Timothy B']",Virol J,,,True
71d134916c750fb6f875d3936a957b27a5df72bc,PMC,Debate around infection-dependent hemophagocytic syndrome in paediatrics,http://dx.doi.org/10.1186/1471-2334-13-15,PMC3549728,23324497,CC BY,"BACKGROUND: Hemophagocytic syndrome (HPS) is clinically defined as a combination of fever, liver dysfunction, coagulation abnormalities, pancytopenia, progressive macrophage proliferation throughout the reticuloendothelial system, and cytokine over-production, and may be primary or secondary to infectious, auto-immune, and tumoral diseases. The most consistent association is with viral infections but, as it is still debated whether any micro-organisms are involved in its pathogenesis, we critically appraised the literature concerning HPS and its relationship with infections. DISCUSSION: Infection-dependent HPS has been widely observed, but there are no data concerning its incidence in children. A better understanding of the pathophysiology of HPS may clarify the interactions between the immune system and the variously implicated potential infectious agents. Epstein-Barr virus (EBV) infection has been prominently associated with HPS, with clonal proliferation and the hyperactivation of EBV-infected T cells. However, a number of other viral, bacterial, fungal, and parasitic infections have been reported in association with HPS. In the case of low-risk HPS, corticosteroids and/or intravenous immunoglobulin or cyclosporine A may be sufficient to control the biological process, but etoposide is recommended as a means of reversing infection-dependent lymphohistiocytic dysregulation in high-risk cases. SUMMARY: HPS is a potential complication of various infections. A polymerase chain reaction search for infectious agents including EBV, cytomegalovirus and Leishmania is recommended in clinical settings characterised by non-remitting fever, organomegaly, cytopenia and hyperferritinemia.",2013 Jan 16,"['Ansuini, Valentina', 'Rigante, Donato', 'Esposito, Susanna']",BMC Infect Dis,,,True
54cbbaf44335fdc1995cb19e5a08779929fd0966,PMC,HIV-1 Fusion Is Blocked through Binding of GB Virus C E2D Peptides to the HIV-1 gp41 Disulfide Loop,http://dx.doi.org/10.1371/journal.pone.0054452,PMC3551756,23349893,CC BY,"A strategy for antiviral drug discovery is the elucidation and imitation of viral interference mechanisms. HIV-1 patients benefit from a coinfection with GB Virus C (GBV-C), since HIV-positive individuals with long-term GBV-C viraemia show better survival rates than HIV-1 patients without persisting GBV-C. A direct influence of GBV-C on HIV-1 replication has been shown in coinfection experiments. GBV-C is a human non-pathogenic member of the flaviviridae family that can replicate in T and B cells. Therefore, GBV-C shares partly the same ecological niche with HIV-1. In earlier work we have demonstrated that recombinant glycoprotein E2 of GBV-C and peptides derived from the E2 N-terminus interfere with HIV entry. In this study we investigated the underlying mechanism. Performing a virus-cell fusion assay and temperature-arrested HIV-infection kinetics, we provide evidence that the HIV-inhibitory E2 peptides interfere with late HIV-1 entry steps after the engagement of gp120 with CD4 receptor and coreceptor. Binding and competition experiments revealed that the N-terminal E2 peptides bind to the disulfide loop region of HIV-1 transmembrane protein gp41. In conjunction with computational analyses, we identified sequence similarities between the N-termini of GBV-C E2 and the HIV-1 glycoprotein gp120. This similarity appears to enable the GBV-C E2 N-terminus to interact with the HIV-1 gp41 disulfide loop, a crucial domain involved in the gp120-gp41 interface. Furthermore, the results of the present study provide initial proof of concept that peptides targeted to the gp41 disulfide loop are able to inhibit HIV fusion and should inspire the development of this new class of HIV-1 entry inhibitors.",2013 Jan 22,"['Eissmann, Kristin', 'Mueller, Sebastian', 'Sticht, Heinrich', 'Jung, Susan', 'Zou, Peng', 'Jiang, Shibo', 'Gross, Andrea', 'Eichler, Jutta', 'Fleckenstein, Bernhard', 'Reil, Heide']",PLoS One,,,True
de22df7c68cc8f64265c0a26ef9f2acd53520ef6,PMC,Chemokine CXCL14 is associated with prognosis in patients with colorectal carcinoma after curative resection,http://dx.doi.org/10.1186/1479-5876-11-6,PMC3551837,23294544,CC BY,"BACKGROUND: The chemokine CXCL14 has been reported to play an important role in the progression of many malignancies such as breast cancer and papillary thyroid carcinoma, but the role of CXCL14 in colorectal carcinoma (CRC) remains to be established. The purpose of this study was to investigate the expression pattern and significance of CXCL14 in CRC progression. METHOD: 265 colorectal carcinoma specimens and 129 matched adjacent normal colorectal mucosa specimens were collected. Expression of CXCL14 in clinical samples was examined by immunostaining. The effect of CXCL14 on colorectal carcinoma cell proliferation was measured by MTT assay, BrdU incorporation assay and colony formation assay. The impact of CXCL14 on migration and invasion of colorectal carcinoma cells was determined by transwell assay and Matrigel invasion assay, respectively. RESULTS: CXCL14 expression was significantly up-regulated in tumor tissues compared with adjacent nontumorous mucosa tissues (P < 0.001). Tumoral CXCL14 expression levels were significantly correlated with TNM (Tumor-node-metastasis) stage, histodifferentiation, and tumor size. In multivariate Cox regression analysis, high CXCL14 expression in tumor specimens (n = 91) from stage I/II patients was associated with increased risk for disease recurrence (risk ratio, 2.92; 95% CI, 1.15-7.40; P = 0.024). Elevated CXCL14 expression in tumor specimens (n = 135) from stage III/IV patients correlated with worse overall survival (risk ratio, 3.087; 95% CI, 1.866-5.107; P < 0.001). Functional studies demonstrated that enforced expression of CXCL14 in SW620 colorectal carcinoma cells resulted in more aggressive phenotypes. In contrast, knockdown of CXCL14 expression could mitigate the proliferative, migratory and invasive potential of HCT116 colorectal carcinoma cells. CONCLUSION: Taken together, CXCL14 might be a potential novel prognostic factor to predict the disease recurrence and overall survival and could be a potential target of postoperative adjuvant therapy in CRC patients.",2013 Jan 7,"['Zeng, Jun', 'Yang, Xudan', 'Cheng, Lin', 'Liu, Rui', 'Lei, Yunlong', 'Dong, Dandan', 'Li, Fanghua', 'Lau, Quek Choon', 'Deng, Longfei', 'Nice, Edouard C', 'Xie, Ke', 'Huang, Canhua']",J Transl Med,,,True
406aad9b3f74f619a1aac3f29ad531b28fb7c37e,PMC,Use of Toll-Like Receptor 3 Agonists Against Respiratory Viral Infections,http://dx.doi.org/10.2174/187152111800194434,PMC3552307,,CC BY,"Respiratory RNA viruses are constantly evolving, thus requiring development of additional prophylactic and therapeutic strategies. Harnessing the innate immune system to non-specifically respond to viral infection has the advantage of being able to circumvent viral mutations that render the virus resistant to a particular therapeutic agent. Viruses are recognized by various cellular receptors, including Toll-like receptor (TLR) 3 which recognizes double-stranded (ds)RNA produced during the viral replication cycle. TLR3 agonists include synthetic dsRNA such as poly (IC), poly (ICLC) and poly (AU). These agents have been evaluated and found to be effective against a number of viral agents. One major limitation has been the toxicity associated with administration of these drugs. Significant time and effort have been spent to develop alternatives/modifications that will minimize these adverse effects. This review will focus on the TLR3 agonist, poly (IC)/(ICLC) with respect to its use in treatment/prevention of respiratory viral infections.",2011 Oct,"['Christopher, ME', 'Wong, JP']",Antiinflamm Antiallergy Agents Med Chem,,,True
d0a7af58aa5e272f1c7aef4e6908dd3059d9173e,PMC,Proteasome inhibition in cancer is associated with enhanced tumor targeting by the adeno‐associated virus/phage,http://dx.doi.org/10.1016/j.molonc.2012.08.001,PMC3553581,22951279,CC BY,"Bacteriophage (phage), which are viruses that infect bacteria only, have shown promise as vehicles for targeted cancer gene therapy, albeit with poor efficiency. Recently, we generated an improved version of phage vectors by incorporating cis genetic elements of adeno‐associated virus (AAV). This novel AAV/phage hybrid (AAVP) efficiently delivered systemically administered therapeutic genes to various tumor targets by displaying an integrin tumor‐targeting ligand on the phage capsid. However, inherent limitations in bacteriophage mean that these AAVP vectors still need to be improved. One of the limitations of AAVP in mammalian cells may be its susceptibility to proteasomal degradation. The proteasome is upregulated in cancer and it is known that it constitutes a barrier to gene delivery by certain eukaryotic viruses. We report here that inhibition of proteasome improved targeted reporter gene delivery by AAVP in cancer cells in vitro and in tumors in vivo after intravenous vector administration to tumor‐bearing mice. We also show enhanced targeted tumor cell killing by AAVP upon proteasome inhibition. The AAVP particles persisted significantly in cancer cells in vitro and in tumors in vivo after systemic administration, and accumulated polyubiquitinated coat proteins. Our results suggest that the proteasome is indeed a barrier to tumor targeting by AAVP and indicate that a combination of proteasome‐inhibiting drugs and AAVP should be considered for clinical anticancer therapy.",2013 Feb 21,"['Przystal, Justyna M.', 'Umukoro, Eloho', 'Stoneham, Charlotte A.', 'Yata, Teerapong', ""O'Neill, Kevin"", 'Syed, Nelofer', 'Hajitou, Amin']",Mol Oncol,,,True
21083480591a0f89c6c6a1ee575c79ef9eeaeb75,PMC,"C-reactive protein, haptoglobin, serum amyloid A and pig major acute phase protein response in pigs simultaneously infected with H1N1 swine influenza virus and Pasteurella multocida",http://dx.doi.org/10.1186/1746-6148-9-14,PMC3554491,23332090,CC BY,"BACKGROUND: Swine influenza (SI) is an acute respiratory disease caused by swine influenza virus (SIV). Swine influenza is generally characterized by acute onset of fever and respiratory symptoms. The most frequent complications of influenza are secondary bacterial pneumonia. The objective of this work was to study the acute phase proteins (APP) responses after coinfection of piglets with H1N1 swine influenza virus (SwH1N1) and Pasteurella multocida (Pm) in order to identify whether the individual APP response correlate with disease severity and whether APP could be used as markers of the health status of coinfected pigs. RESULTS: In all coinfected pigs clinical sings, including fever, coughing and dyspnea, were seen. Viral shedding was observed from 2 to 7 dpi. The mean level of antibodies against Pm dermonecrotoxin in infected piglets increase significantly from 7 dpi. Anti-SwH1N1 antibodies in the serum were detected from 7 dpi. The concentration of C-reactive protein (CRP) increased significantly at 1 dpi as compared to control pigs, and remained significantly higher to 3 dpi. Level of serum amyloid A (SAA) was significantly higher from 2 to 3 dpi. Haptoglobin (Hp) was significantly elevated from 3 dpi to the end of study, while pig major acute phase protein (Pig-MAP) from 3 to 7 dpi. The concentrations of CRP, Hp and SAA significantly increased before specific antibodies were detected. Positive correlations were found between serum concentration of Hp and SAA and lung scores, and between clinical score and concentrations of Pig-MAP and SAA. CONCLUSIONS: The results of current study confirmed that monitoring of APP may revealed ongoing infection, and in this way may be useful in selecting clinically healthy pigs (i.e. before integration into an uninfected herd). Present results corroborated our previous findings that SAA could be a potentially useful indicator in experimental infection studies (e.g. vaccine efficiency investigations) or as a marker for disease severity, because of correlation observed between its concentration in serum and disease severity (lung scores, clinical scores).",2013 Jan 18,"['Pomorska-Mól, Małgorzata', 'Markowska-Daniel, Iwona', 'Kwit, Krzysztof', 'Stępniewska, Katarzyna', 'Pejsak, Zygmunt']",BMC Vet Res,,,True
1ca045bd7724943ce8c268353153bd522358625d,PMC,Positional Bias of MHC Class I Restricted T-Cell Epitopes in Viral Antigens Is Likely due to a Bias in Conservation,http://dx.doi.org/10.1371/journal.pcbi.1002884,PMC3554532,23357871,CC0,"The immune system rapidly responds to intracellular infections by detecting MHC class I restricted T-cell epitopes presented on infected cells. It was originally thought that viral peptides are liberated during constitutive protein turnover, but this conflicts with the observation that viral epitopes are detected within minutes of their synthesis even when their source proteins exhibit half-lives of days. The DRiPs hypothesis proposes that epitopes derive from Defective Ribosomal Products (DRiPs), rather than degradation of mature protein products. One potential source of DRiPs is premature translation termination. If this is a major source of DRiPs, this should be reflected in positional bias towards the N-terminus. By contrast, if downstream initiation is a major source of DRiPs, there should be positional bias towards the C-terminus. Here, we systematically assessed positional bias of epitopes in viral antigens, exploiting the large set of data available in the Immune Epitope Database and Analysis Resource. We show a statistically significant degree of positional skewing among epitopes; epitopes from both ends of antigens tend to be under-represented. Centric-skewing correlates with a bias towards class I binding peptides being over-represented in the middle, in parallel with a higher degree of evolutionary conservation.",2013 Jan 24,"['Kim, Yohan', 'Yewdell, Jonathan W.', 'Sette, Alessandro', 'Peters, Bjoern']",PLoS Comput Biol,,,True
5e11e3105842cf7cedf10e26bff170a52c23cf00,PMC,IFITM Proteins Restrict Viral Membrane Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1003124,PMC3554583,23358889,CC BY,"The interferon-inducible transmembrane (IFITM) protein family represents a new class of cellular restriction factors that block early stages of viral replication; the underlying mechanism is currently not known. Here we provide evidence that IFITM proteins restrict membrane fusion induced by representatives of all three classes of viral membrane fusion proteins. IFITM1 profoundly suppressed syncytia formation and cell-cell fusion induced by almost all viral fusion proteins examined; IFITM2 and IFITM3 also strongly inhibited their fusion, with efficiency somewhat dependent on cell types. Furthermore, treatment of cells with IFN also markedly inhibited viral membrane fusion and entry. By using the Jaagsiekte sheep retrovirus envelope and influenza A virus hemagglutinin as models for study, we showed that IFITM-mediated restriction on membrane fusion is not at the steps of receptor- and/or low pH-mediated triggering; instead, the creation of hemifusion was essentially blocked by IFITMs. Chlorpromazine (CPZ), a chemical known to promote the transition from hemifusion to full fusion, was unable to rescue the IFITM-mediated restriction on fusion. In contrast, oleic acid (OA), a lipid analog that generates negative spontaneous curvature and thereby promotes hemifusion, virtually overcame the restriction. To explore the possible effect of IFITM proteins on membrane molecular order and fluidity, we performed fluorescence labeling with Laurdan, in conjunction with two-photon laser scanning and fluorescence-lifetime imaging microscopy (FLIM). We observed that the generalized polarizations (GPs) and fluorescence lifetimes of cell membranes expressing IFITM proteins were greatly enhanced, indicating higher molecularly ordered and less fluidized membranes. Collectively, our data demonstrated that IFITM proteins suppress viral membrane fusion before the creation of hemifusion, and suggested that they may do so by reducing membrane fluidity and conferring a positive spontaneous curvature in the outer leaflets of cell membranes. Our study provides novel insight into the understanding of how IFITM protein family restricts viral membrane fusion and infection.",2013 Jan 24,"['Li, Kun', 'Markosyan, Ruben M.', 'Zheng, Yi-Min', 'Golfetto, Ottavia', 'Bungart, Brittani', 'Li, Minghua', 'Ding, Shilei', 'He, Yuxian', 'Liang, Chen', 'Lee, James C.', 'Gratton, Enrico', 'Cohen, Fredric S.', 'Liu, Shan-Lu']",PLoS Pathog,,,True
1f4ec41f723e758522faa99829a52f00ea45a9e2,PMC,Aerobiology and Its Role in the Transmission of Infectious Diseases,http://dx.doi.org/10.1155/2013/493960,PMC3556854,23365758,CC BY,"Aerobiology plays a fundamental role in the transmission of infectious diseases. As infectious disease and infection control practitioners continue employing contemporary techniques (e.g., computational fluid dynamics to study particle flow, polymerase chain reaction methodologies to quantify particle concentrations in various settings, and epidemiology to track the spread of disease), the central variables affecting the airborne transmission of pathogens are becoming better known. This paper reviews many of these aerobiological variables (e.g., particle size, particle type, the duration that particles can remain airborne, the distance that particles can travel, and meteorological and environmental factors), as well as the common origins of these infectious particles. We then review several real-world settings with known difficulties controlling the airborne transmission of infectious particles (e.g., office buildings, healthcare facilities, and commercial airplanes), while detailing the respective measures each of these industries is undertaking in its effort to ameliorate the transmission of airborne infectious diseases.",2013 Jan 13,"['Fernstrom, Aaron', 'Goldblatt, Michael']",J Pathog,,,True
aac395d967bf4ce6affb506eb9cf5f1bf853e69f,PMC,Coronavirus infections in hospitalized pediatric patients with acute respiratory tract disease,http://dx.doi.org/10.1186/1471-2334-12-365,PMC3557153,23256846,CC BY,"BACKGROUND: Acute viral respiratory infections are an important cause of morbidity and mortality in humans worldwide. The etiological backgrounds of these infections remain unconfirmed in most clinical cases. The aim of this study was to estimate the prevalence of human coronavirus infections in a series of children hospitalized with symptoms of acute respiratory tract disease in a one-year period in Slovenia. METHODS: The 664 specimens from 592 children under six years of age hospitalized at the University Children’s Hospital in Ljubljana were sent for the routine laboratory detection of respiratory viruses. Respiratory viruses were detected with a direct immunofluorescence assay and human coronaviruses were detected with a modified real-time RT–PCR. RESULTS: HCoV RNA was detected in 40 (6%, 95% CI: 4.3%–8.1%) of 664 samples. Of these specimens, 21/40 (52.5%) were identified as species HKU1, 7/40 (17.5%) as OC43, 6/40 (15%) as 229E, and 6/40 (15%) as NL63. Infection with HCoV occurred as a coinfection with one or more other viruses in most samples (70%). Of the HCoV-positive children, 70.3% had lower respiratory tract infections. CONCLUSION: The results of our study show that HCoV are frequently detected human pathogens, often associated with other respiratory viruses and acute respiratory tract infections in hospitalized children. An association between age and the viral load was found. The highest viral load was detected in children approximately 10 months of age.",2012 Dec 20,"['Jevšnik, Monika', 'Uršič, Tina', 'Žigon, Nina', 'Lusa, Lara', 'Krivec, Uroš', 'Petrovec, Miroslav']",BMC Infect Dis,,,True
884b19f49da8930b2222b5669f387ed974d1f3f3,PMC,Mekong Basin Disease Surveillance (MBDS): A Trust-Based Network,http://dx.doi.org/10.3402/ehtj.v6i0.19944,PMC3557908,23362411,CC BY,"The Mekong Basin Disease Surveillance (MBDS) network was formally established in 2001 through a Memorandum of Understanding signed by six Ministers of Health of the countries in the Greater Mekong sub-region: Cambodia, China (Yunnan and Guangxi), Lao PDR, Myanmar, Thailand and Vietnam. The main areas of focus of the network are to: i) improve cross-border infectious disease outbreak investigation and response by sharing surveillance data and best practices in disease recognition and reporting, and by jointly responding to outbreaks; ii) develop expertise in epidemiological surveillance across the countries; and iii) enhance communication between the countries. Comprised of senior health officials, epidemiologists, health practitioners, and other professionals, the MBDS has grown and matured over the years into an entity based on mutual trust that can be sustained into the future. Other regions have started emulating the network's pioneering work. In this paper, we describe the development of MBDS, the way in which it operates today, and some of its achievements. We present key challenges the network has faced and lessons its members have learned about how to develop sufficient trust for health and other professionals to alert each other to disease threats across national borders and thereby more effectively combat these threats.",2013 Jan 25,"['Phommasack, Bounlay', 'Jiraphongsa, Chuleeporn', 'Ko Oo, Moe', 'Bond, Katherine C.', 'Phaholyothin, Natalie', 'Suphanchaimat, Rapeepong', 'Ungchusak, Kumnuan', 'Macfarlane, Sarah B.']",Emerg Health Threats J,,,True
0ca675e1d62eeff5188b3cfa32f4cf16ea634dc4,PMC,Enhanced Surveillance for Detection and Management of Infectious Diseases: Regional Collaboration in the Middle East,http://dx.doi.org/10.3402/ehtj.v6i0.19955,PMC3557910,23362413,CC BY,"Formed before international negotiations of the revised International Health Regulations (IHR), the Middle East Consortium for Infectious Disease Surveillance (MECIDS) is a regional collaboration aimed at facilitating implementation of the revised IHR and, more broadly, improving the detection and control of infectious disease outbreaks among neighboring countries in an area of continuous dispute. Initially focused on enhancing foodborne disease surveillance, MECIDS has expanded the scope of its work to also include avian and pandemic influenza and other emerging and re-emerging infectious diseases. Here, we describe the history and governance of MECIDS, highlighting key achievements over the consortium's seven-year history, and discuss the future of MECIDS.",2013 Jan 25,"['Leventhal, Alex', 'Ramlawi, Assad', 'Belbiesi, Adel', 'Sheikh, Sami', 'Haddadin, Akhtam', 'Husseini, Sari', 'Abdeen, Ziad', 'Cohen, Dani']",Emerg Health Threats J,,,True
04abbb8d91bd1a15a6c70ce3c0bd339f92468265,PMC,Key Findings and Lessons from an Evaluation of the Rockefeller Foundation's Disease Surveillance Networks Initiative,http://dx.doi.org/10.3402/ehtj.v6i0.19959,PMC3557955,23362418,CC BY,,2013 Jan 25,"['MacPherson, Nancy', 'Kimball, Ann Marie', 'Burke, Charlanne', 'Abernethy, Neil', 'Tempongko, Sandra', 'Zinsstag, Jakob']",Emerg Health Threats J,,,True
437c2f5c3e920111eb679f26bde02cbb8a49ff49,PMC,Development of an improved polykaryon-based influenza virus rescue system,http://dx.doi.org/10.1186/1472-6750-12-69,PMC3558383,23009349,CC BY,"BACKGROUND: Virus rescue from transfected cells is an extremely useful technique that allows defined viral clones to be engineered for the purpose of rational vaccine design or fundamental reverse genetics studies. However, it is often hindered by low primary rescue success rates or yields, especially with field-derived viral strains. APPROACH: We investigated the possibility of enhancing influenza virus rescue by eliciting cell fusion to increase the chances of having all necessary plasmids expressed within the same polykaryon. To this end we used the Maedi-Visna Virus envelope protein which has potent fusion activity in cells from a wide range of different species. RESULTS: Co-transfecting cells with the eight plasmids necessary to rescue influenza virus plus a plasmid expressing the Maedi-Visna Virus envelope protein resulted in increased rescue efficiency. In addition, partial complements of the 8-plasmid rescue system could be transfected into two separate populations of cells, which upon fusion led to live virus rescue. CONCLUSION: The simple modification described here has the potential to improve the efficiency of the virus rescue process and expand the potential applications for reverse genetic studies.",2012 Sep 25,"['Bourret, Vincent', 'Lyall, Jon', 'Ducatez, Mariette F', 'Guérin, Jean-Luc', 'Tiley, Laurence']",BMC Biotechnol,,,True
7f5ef8185f8934ab5b5eb4344dad20da84d104a3,PMC,Detection of Bocavirus in Children Suffering from Acute Respiratory Tract Infections in Saudi Arabia,http://dx.doi.org/10.1371/journal.pone.0055500,PMC3559585,23383205,CC BY,"Human bocavirus (HBoV) was recently discovered in children with respiratory distress and/or diarrhea. To our knowledge, no previous study has reported the existence of bocavirus in Saudi Arabia. Swabs samples from 80 children with respiratory tract infections were examined for the presence of HBoV. Real-time polymerase chain reaction was used as a sensitive method to detect the HBoV. Direct gene sequencing was used to determine the genotype of the detected virus isolates. HBoV was detected in 22.5% of the examined patients. The NP1 partial gene sequence from all patients showed that the circulated strains were related to HBoV-1 genotype. Most of HBoV infected patients showed evidence of mixed coinfection with other viral pathogens. The current study clearly demonstrated that genetically conserved HBoV1 circulates in Saudi Arabia. Interestingly, most of the HBoV1 infected cases were associated with high rates of co-infections with other viruses.",2013 Jan 30,"['Abdel-Moneim, Ahmed S.', 'Kamel, Mahmoud M.', 'Al-Ghamdi, Abdullhamid S.', 'Al-Malky, Mater I. R.']",PLoS One,,,True
16a04dc7659daf72dfd1706f843b74d691048b6f,PMC,Porcine epidemic diarrhea virus E protein causes endoplasmic reticulum stress and up-regulates interleukin-8 expression,http://dx.doi.org/10.1186/1743-422X-10-26,PMC3560205,23332027,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is an important pathogen in swine and is responsible for substantial economic losses. Previous studies suggest that the PEDV E protein plays an important role in the viral assembly process. However, the subcellular localization and other functions of PEDV E protein still require more research. METHODS: The subcellular localization and function of PEDV E protein were investigated by examining its effects on cell growth, cell cycle progression, interleukin-8 (IL-8) expression and cell survival. RESULTS: The results show that plenty of PEDV E protein is localized in the ER, with small quantities localized in the nucleus. The PEDV E protein has no effect on the intestinal epithelial cells (IEC) growth, cell cycle and cyclin A expression. The cells expressing PEDV E protein express higher levels of IL-8 than control cells. Further studies show that PEDV E protein induced endoplasmic reticulum (ER) stress and activated NF-κB which is responsible for the up-regulation of IL-8 and Bcl-2 expression. CONCLUSIONS: This study shows that the PEDV E protein is localized in the ER and the nucleus and it can cause ER stress. The PEDV E protein had no effect on the IEC growth and cell cycle. In addition, the PEDV E protein is able to up-regulate IL-8 and Bcl-2 expression.",2013 Jan 19,"['Xu, Xingang', 'Zhang, Honglei', 'Zhang, Qi', 'Dong, Jie', 'Liang, Yabing', 'Huang, Yong', 'Liu, Hung-Jen', 'Tong, Dewen']",Virol J,,,True
0c58c5ce46bfa52188d231685cc1c6a440840b85,PMC,Epidemiology and clinical presentation of the four human parainfluenza virus types,http://dx.doi.org/10.1186/1471-2334-13-28,PMC3560251,23343342,CC BY,"BACKGROUND: Human parainfluenza viruses (HPIVs) are important causes of upper respiratory tract illness (URTI) and lower respiratory tract illness (LRTI). To analyse epidemiologic and clinical characteristics of the four types of human parainfluenza viruses (HPIVs), patients with acute respiratory tract illness (ARTI) were studied in Guangzhou, southern China. METHODS: Throat swabs (n=4755) were collected and tested from children and adults with ARTI over a 26-month period, and 4447 of 4755 (93.5%) patients’ clinical presentations were recorded for further analysis. RESULTS: Of 4755 patients tested, 178 (3.7%) were positive for HPIV. Ninety-nine (2.1%) samples were positive for HPIV-3, 58 (1.2%) for HPIV-1, 19 (0.4%) for HPIV-2 and 8 (0.2%) for HPIV-4. 160/178 (88.9%) HPIV-positive samples were from paediatric patients younger than 5 years old, but no infant under one month of age was HPIV positive. Seasonal peaks of HPIV-3 and HPIV-1 occurred as autumn turned to winter and summer turned to autumn. HPIV-2 and HPIV-4 were detected less frequently, and their frequency of isolation increased when the frequency of HPIV-3 and HPIV-1 declined. HPIV infection led to a wide spectrum of symptoms, and more “hoarseness” (p=0.015), “abnormal pulmonary breathing sound” (p<0.001), “dyspnoea” (p<0.001), “pneumonia” (p=0.01), and “diarrhoea” (p<0.001) presented in HPIV-positive patients than HPIV-negative patients. 10/10 (100%) HPIV-positive adult patients (≥14 years old) presented with systemic influenza-like symptoms, while 90/164 (54.9%) HPIV-positive paediatric patients (<14 years old) presented with these symptoms (p=0.005). The only significant difference in clinical presentation between HPIV types was “Expectoration” (p<0.001). Co-infections were common, with 33.3%–63.2% of samples positive for the four HPIV types also testing positive for other respiratory pathogens. However, no significant differences were seen in clinical presentation between patients solely infected with HPIV and patients co-infected with HPIV and other respiratory pathogens. CONCLUSIONS: HPIV infection led to a wide spectrum of symptoms, and similar clinical manifestations were found in the patients with four different types of HPIVs. The study suggested pathogenic activity of HPIV in gastrointestinal illness. The clinical presentation of HPIV infection may differ by patient age.",2013 Jan 23,"['Liu, Wen-Kuan', 'Liu, Qian', 'Chen, De-Hui', 'Liang, Huan-Xi', 'Chen, Xiao-Kai', 'Huang, Wen-Bo', 'Qin, Sheng', 'Yang, Zi-Feng', 'Zhou, Rong']",BMC Infect Dis,,,True
34e4b49c46c5462089f516983eeb19a6aff69d01,PMC,Inflammatory monocytes and the pathogenesis of viral encephalitis,http://dx.doi.org/10.1186/1742-2094-9-270,PMC3560265,23244217,CC BY,"Monocytes are a heterogeneous population of bone marrow-derived cells that are recruited to sites of infection and inflammation in many models of human diseases, including those of the central nervous system (CNS). Ly6C(hi)/CCR2(hi) inflammatory monocytes have been identified as the circulating precursors of brain macrophages, dendritic cells and arguably microglia in experimental autoimmune encephalomyelitis; Alzheimer’s disease; stroke; and more recently in CNS infection caused by Herpes simplex virus, murine hepatitis virus, Theiler’s murine encephalomyelitis virus, Japanese encephalitis virus and West Nile virus. The precise differentiation pathways and functions of inflammatory monocyte-derived populations in the inflamed CNS remains a contentious issue, especially in regard to the existence of monocyte-derived microglia. Furthermore, the contributions of monocyte-derived subsets to viral clearance and immunopathology are not well-defined. Thus, understanding the pathways through which inflammatory monocytes migrate to the brain and their functional capacity within the CNS is critical to inform future therapeutic strategies. This review discusses some of the key aspects of inflammatory monocyte trafficking to the brain and addresses the role of these cells in viral encephalitis.",2012 Dec 17,"['Terry, Rachael L', 'Getts, Daniel R', 'Deffrasnes, Celine', 'van Vreden, Caryn', 'Campbell, Iain L', 'King, Nicholas JC']",J Neuroinflammation,,,True
50c7a780f9115d0224ceeb6f2e29037d8e5703d8,PMC,Unraveling the Structure of Viral Replication Complexes at Super-Resolution,http://dx.doi.org/10.3389/fpls.2013.00006,PMC3560349,23386855,CC BY,"During infection, many RNA viruses produce characteristic inclusion bodies that contain both viral and host components. These structures were first described over a century ago and originally termed “X-bodies,” as their function was not immediately appreciated. Whilst some inclusion bodies may represent cytopathic by-products of viral protein over-accumulation, X-bodies have emerged as virus “factories,” quasi-organelles that coordinate diverse viral infection processes such as replication, protein expression, evasion of host defenses, virion assembly, and intercellular transport. Accordingly, they are now generally referred to as viral replication complexes (VRCs). We previously used confocal fluorescence microscopy to unravel the complex structure of X-bodies produced by Potato virus X (PVX). Here we used 3D-structured illumination (3D-SIM) super-resolution microscopy to map the PVX X-body at a finer scale. We identify a previously unrecognized membrane structure induced by the PVX “triple gene block” (TGB) proteins, providing new insights into the complex interplay between virus and host within the X-body.",2013 Jan 31,"['Linnik, Olga', 'Liesche, Johannes', 'Tilsner, Jens', 'Oparka, Karl J.']",Front Plant Sci,,,True
19dcbc62263225d430f506aa5745d23a66543de8,PMC,Binding of HIV-1 gp120 to DC-SIGN Promotes ASK-1-Dependent Activation-Induced Apoptosis of Human Dendritic Cells,http://dx.doi.org/10.1371/journal.ppat.1003100,PMC3561151,23382671,CC BY,"During disease progression to AIDS, HIV-1 infected individuals become increasingly immunosuppressed and susceptible to opportunistic infections. It has also been demonstrated that multiple subsets of dendritic cells (DC), including DC-SIGN(+) cells, become significantly depleted in the blood and lymphoid tissues of AIDS patients, which may contribute to the failure in initiating effective host immune responses. The mechanism for DC depletion, however, is unclear. It is also known that vast quantities of viral envelope protein gp120 are shed from maturing HIV-1 virions and form circulating immune complexes in the serum of HIV-1-infected individuals, but the pathological role of gp120 in HIV-1 pathogenesis remains elusive. Here we describe a previously unrecognized mechanism of DC death in chronic HIV-1 infection, in which ligation of DC-SIGN by gp120 sensitizes DC to undergo accelerated apoptosis in response to a variety of activation stimuli. The cultured monocyte-derived DC and also freshly-isolated DC-SIGN(+) blood DC that were exposed to either cross-linked recombinant gp120 or immune-complex gp120 in HIV(+) serum underwent considerable apoptosis after CD40 ligation or exposure to bacterial lipopolysaccharide (LPS) or pro-inflammatory cytokines such as TNFα and IL-1β. Furthermore, circulating DC-SIGN(+) DC that were isolated directly from HIV-1(+) individuals had actually been pre-sensitized by serum gp120 for activation-induced exorbitant apoptosis. In all cases the DC apoptosis was substantially inhibited by DC-SIGN blockade. Finally, we showed that accelerated DC apoptosis was a direct consequence of excessive activation of the pro-apoptotic molecule ASK-1 and transfection of siRNA against ASK-1 significantly prevented the activation-induced excessive DC death. Our study discloses a previously unknown mechanism of immune modulation by envelope protein gp120, provides new insights into HIV immunopathogenesis, and suggests potential therapeutic approaches to prevent DC depletion in chronic HIV infection.",2013 Jan 31,"['Chen, Yongxiong', 'Hwang, Shiuh-Lin', 'Chan, Vera S. F.', 'Chung, Nancy P. Y.', 'Wang, Shu-Rong', 'Li, Zhongye', 'Ma, Jing', 'Lin, Chia-Wei', 'Hsieh, Ya-Ju', 'Chang, Kao-Ping', 'Kung, Sui-Sum', 'Wu, Yi-Chia', 'Chu, Cheng-Wei', 'Tai, Hsiao-Ting', 'Gao, George F.', 'Zheng, Bojian', 'Yokoyama, Kazunari K.', 'Austyn, Jonathan M.', 'Lin, Chen-Lung S.']",PLoS Pathog,,,True
5efae4eb4c986da7483e7628d420be2a29df90d0,PMC,Differential Response of Primary Alveolar Type I and Type II Cells to LPS Stimulation,http://dx.doi.org/10.1371/journal.pone.0055545,PMC3561226,23383221,CC0,"The alveolar epithelium serves as a barrier between organism and environment and functions as the first line of protection against potential respiratory pathogens. Alveolar type II (TII) cells have traditionally been considered the immune cells of the alveolar epithelium, as they possess immunomodulatory functions; however, the precise role of alveolar type I (TI) cells, which comprise ∼95% of the alveolar epithelial surface area, in lung immunity is not clear. We sought to determine if there was a difference in the response of TI and TII cells to lung injury and if TI cells could actively participate in the alveolar immune response. TI cells isolated via fluorescence activated cell sorting (FACS) from LPS-injured rats demonstrated greater fold-induction of multiple inflammatory mediators than TII cells isolated in the same manner from the same animals. Levels of the cytokines TNF-α, IL-6 and IL-1β from cultured primary rat TI cells after LPS stimulation were significantly increased compared to similarly studied primary rat TII cells. We found that contrary to published reports, cultured TII cells produce relatively small amounts of TNF-α, IL-6 and IL-1β after LPS treatment; the higher levels of cytokine expression from cultured TII cells reported in the literature were likely from macrophage contamination due to traditional non-FACS TII cell isolation methods. Co-culture of TII cells with macrophages prior to LPS stimulation increased TNF-α and IL-6 production to levels reported by other investigators for TII cells, however, co-culture of TI cells and macrophages prior to LPS treatment resulted in marked increases in TNF-α and IL-6 production. Finally, exogenous surfactant blunted the IL-6 response to LPS in cultured TI cells. Taken together, these findings advocate a role for TI cells in the innate immune response and suggest that both TI and TII cells are active players in host defense mechanisms in the lung.",2013 Jan 31,"['Wong, Mandi H.', 'Johnson, Meshell D.']",PLoS One,,,True
83f15da5d4de38afb2d1ba4b482f66d4e623c11e,PMC,An Upstream Open Reading Frame Modulates Ebola Virus Polymerase Translation and Virus Replication,http://dx.doi.org/10.1371/journal.ppat.1003147,PMC3561295,23382680,CC0,"Ebolaviruses, highly lethal zoonotic pathogens, possess longer genomes than most other non-segmented negative-strand RNA viruses due in part to long 5′ and 3′ untranslated regions (UTRs) present in the seven viral transcriptional units. To date, specific functions have not been assigned to these UTRs. With reporter assays, we demonstrated that the Zaire ebolavirus (EBOV) 5′-UTRs lack internal ribosomal entry site function. However, the 5′-UTRs do differentially regulate cap-dependent translation when placed upstream of a GFP reporter gene. Most dramatically, the 5′-UTR derived from the viral polymerase (L) mRNA strongly suppressed translation of GFP compared to a β-actin 5′-UTR. The L 5′-UTR is one of four viral genes to possess upstream AUGs (uAUGs), and ablation of each uAUG enhanced translation of the primary ORF (pORF), most dramatically in the case of the L 5′-UTR. The L uAUG was sufficient to initiate translation, is surrounded by a “weak” Kozak sequence and suppressed pORF translation in a position-dependent manner. Under conditions where eIF2α was phosphorylated, the presence of the uORF maintained translation of the L pORF, indicating that the uORF modulates L translation in response to cellular stress. To directly address the role of the L uAUG in virus replication, a recombinant EBOV was generated in which the L uAUG was mutated to UCG. Strikingly, mutating two nucleotides outside of previously-defined protein coding and cis-acting regulatory sequences attenuated virus growth to titers 10–100-fold lower than a wild-type virus in Vero and A549 cells. The mutant virus also exhibited decreased viral RNA synthesis as early as 6 hours post-infection and enhanced sensitivity to the stress inducer thapsigargin. Cumulatively, these data identify novel mechanisms by which EBOV regulates its polymerase expression, demonstrate their relevance to virus replication and identify a potential therapeutic target.",2013 Jan 31,"['Shabman, Reed S.', 'Hoenen, Thomas', 'Groseth, Allison', 'Jabado, Omar', 'Binning, Jennifer M.', 'Amarasinghe, Gaya K.', 'Feldmann, Heinz', 'Basler, Christopher F.']",PLoS Pathog,,,True
a65ed49e9217467923e8db733109be6e54b0bd09,PMC,Quantitative analysis of ciliary beating in primary ciliary dyskinesia: a pilot study,http://dx.doi.org/10.1186/1750-1172-7-78,PMC3562218,23057704,CC BY,"BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare congenital respiratory disorder characterized by abnormal ciliary motility leading to chronic airway infections. Qualitative evaluation of ciliary beat pattern based on digital high-speed videomicroscopy analysis has been proposed in the diagnosis process of PCD. Although this evaluation is easy in typical cases, it becomes difficult when ciliary beating is partially maintained. We postulated that a quantitative analysis of beat pattern would improve PCD diagnosis. We compared quantitative parameters with the qualitative evaluation of ciliary beat pattern in patients in whom the diagnosis of PCD was confirmed or excluded. METHODS: Nasal nitric oxide measurement, nasal brushings and biopsies were performed prospectively in 34 patients with suspected PCD. In combination with qualitative analysis, 12 quantitative parameters of ciliary beat pattern were determined on high-speed videomicroscopy recordings of beating ciliated edges. The combination of ciliary ultrastructural abnormalities on transmission electron microscopy analysis with low nasal nitric oxide levels was the “gold standard” used to establish the diagnosis of PCD. RESULTS: This “gold standard” excluded PCD in 15 patients (non-PCD patients), confirmed PCD in 10 patients (PCD patients) and was inconclusive in 9 patients. Among the 12 parameters, the distance traveled by the cilium tip weighted by the percentage of beating ciliated edges presented 96% sensitivity and 95% specificity. Qualitative evaluation and quantitative analysis were concordant in non-PCD patients. In 9/10 PCD patients, quantitative analysis was concordant with the “gold standard”, while the qualitative evaluation was discordant with the “gold standard” in 3/10 cases. Among the patients with an inconclusive “gold standard”, the use of quantitative parameters supported PCD diagnosis in 4/9 patients (confirmed by the identification of disease-causing mutations in one patient) and PCD exclusion in 2/9 patients. CONCLUSIONS: When the beat pattern is normal or virtually immotile, the qualitative evaluation is adequate to study ciliary beating in patients suspected for PCD. However, when cilia are still beating but with moderate alterations (more than 40% of patients suspected for PCD), quantitative analysis is required to precise the diagnosis and can be proposed to select patients eligible for TEM.",2012 Oct 11,"['Papon, Jean-François', 'Bassinet, Laurence', 'Cariou-Patron, Gwenaëlle', 'Zerah-Lancner, Francoise', 'Vojtek, Anne-Marie', 'Blanchon, Sylvain', 'Crestani, Bruno', 'Amselem, Serge', 'Coste, Andre', 'Housset, Bruno', 'Escudier, Estelle', 'Louis, Bruno']",Orphanet J Rare Dis,,,True
d148bed5cf622c1a263907a3cbf8c6d533edded8,PMC,Inhibitors of the Influenza A Virus M2 Proton Channel Discovered Using a High-Throughput Yeast Growth Restoration Assay,http://dx.doi.org/10.1371/journal.pone.0055271,PMC3562233,23383318,CC BY,"The M2 proton channel of the influenza A virus is the target of the anti-influenza drugs amantadine and rimantadine. The effectiveness of these drugs has been dramatically limited by the rapid spread of drug resistant mutations, mainly at sites S31N, V27A and L26F in the pore of the channel. Despite progress in designing inhibitors of V27A and L26F M2, there are currently no drugs targeting these mutated channels in clinical trials. Progress in developing new drugs has been hampered by the lack of a robust assay with sufficient throughput for discovery of new active chemotypes among chemical libraries and sufficient sensitivity to provide the SAR data essential for their improvement and development as drugs. In this study we adapted a yeast growth restoration assay, in which expression of the M2 channel inhibits yeast growth and exposure to an M2 channel inhibitor restores growth, into a robust and sensitive high-throughput screen for M2 channel inhibitors. A screen of over 250,000 pure chemicals and semi-purified fractions from natural extracts identified 21 active compounds comprising amantadine, rimantadine, 13 related adamantanes and 6 non-adamantanes. Of the non-adamantanes, hexamethylene amiloride and a triazine derivative represented new M2 inhibitory chemotypes that also showed antiviral activity in a plaque reduction assay. Of particular interest is the fact that the triazine derivative was not sufficiently potent for detection as an inhibitor in the traditional two electrode voltage clamp assay for M2 channel activity, but its discovery in the yeast assay led to testing of analogues of which one was as potent as amantadine.",2013 Feb 1,"['Balgi, Aruna D.', 'Wang, Jun', 'Cheng, Daphne Y. H.', 'Ma, Chunlong', 'Pfeifer, Tom A.', 'Shimizu, Yoko', 'Anderson, Hilary J.', 'Pinto, Lawrence H.', 'Lamb, Robert A.', 'DeGrado, William F.', 'Roberge, Michel']",PLoS One,,,True
1cc437f58a3eda9fc4e73c1cabb18964d2a7e705,PMC,Inhibitors of the Influenza A Virus M2 Proton Channel Discovered Using a High-Throughput Yeast Growth Restoration Assay,http://dx.doi.org/10.1371/journal.pone.0055271,PMC3562233,23383318,CC BY,"The M2 proton channel of the influenza A virus is the target of the anti-influenza drugs amantadine and rimantadine. The effectiveness of these drugs has been dramatically limited by the rapid spread of drug resistant mutations, mainly at sites S31N, V27A and L26F in the pore of the channel. Despite progress in designing inhibitors of V27A and L26F M2, there are currently no drugs targeting these mutated channels in clinical trials. Progress in developing new drugs has been hampered by the lack of a robust assay with sufficient throughput for discovery of new active chemotypes among chemical libraries and sufficient sensitivity to provide the SAR data essential for their improvement and development as drugs. In this study we adapted a yeast growth restoration assay, in which expression of the M2 channel inhibits yeast growth and exposure to an M2 channel inhibitor restores growth, into a robust and sensitive high-throughput screen for M2 channel inhibitors. A screen of over 250,000 pure chemicals and semi-purified fractions from natural extracts identified 21 active compounds comprising amantadine, rimantadine, 13 related adamantanes and 6 non-adamantanes. Of the non-adamantanes, hexamethylene amiloride and a triazine derivative represented new M2 inhibitory chemotypes that also showed antiviral activity in a plaque reduction assay. Of particular interest is the fact that the triazine derivative was not sufficiently potent for detection as an inhibitor in the traditional two electrode voltage clamp assay for M2 channel activity, but its discovery in the yeast assay led to testing of analogues of which one was as potent as amantadine.",2013 Feb 1,"['Balgi, Aruna D.', 'Wang, Jun', 'Cheng, Daphne Y. H.', 'Ma, Chunlong', 'Pfeifer, Tom A.', 'Shimizu, Yoko', 'Anderson, Hilary J.', 'Pinto, Lawrence H.', 'Lamb, Robert A.', 'DeGrado, William F.', 'Roberge, Michel']",PLoS One,,,False
97d3189bef9a6aa37975b4fe0da23c7c0ea1dae9,PMC,Inhibitors of the Influenza A Virus M2 Proton Channel Discovered Using a High-Throughput Yeast Growth Restoration Assay,http://dx.doi.org/10.1371/journal.pone.0055271,PMC3562233,23383318,CC BY,"The M2 proton channel of the influenza A virus is the target of the anti-influenza drugs amantadine and rimantadine. The effectiveness of these drugs has been dramatically limited by the rapid spread of drug resistant mutations, mainly at sites S31N, V27A and L26F in the pore of the channel. Despite progress in designing inhibitors of V27A and L26F M2, there are currently no drugs targeting these mutated channels in clinical trials. Progress in developing new drugs has been hampered by the lack of a robust assay with sufficient throughput for discovery of new active chemotypes among chemical libraries and sufficient sensitivity to provide the SAR data essential for their improvement and development as drugs. In this study we adapted a yeast growth restoration assay, in which expression of the M2 channel inhibits yeast growth and exposure to an M2 channel inhibitor restores growth, into a robust and sensitive high-throughput screen for M2 channel inhibitors. A screen of over 250,000 pure chemicals and semi-purified fractions from natural extracts identified 21 active compounds comprising amantadine, rimantadine, 13 related adamantanes and 6 non-adamantanes. Of the non-adamantanes, hexamethylene amiloride and a triazine derivative represented new M2 inhibitory chemotypes that also showed antiviral activity in a plaque reduction assay. Of particular interest is the fact that the triazine derivative was not sufficiently potent for detection as an inhibitor in the traditional two electrode voltage clamp assay for M2 channel activity, but its discovery in the yeast assay led to testing of analogues of which one was as potent as amantadine.",2013 Feb 1,"['Balgi, Aruna D.', 'Wang, Jun', 'Cheng, Daphne Y. H.', 'Ma, Chunlong', 'Pfeifer, Tom A.', 'Shimizu, Yoko', 'Anderson, Hilary J.', 'Pinto, Lawrence H.', 'Lamb, Robert A.', 'DeGrado, William F.', 'Roberge, Michel']",PLoS One,,,False
f4f36a8e9fee64d59ccf22b724c7dab345102658,PMC,One step closer to an experimental infection system for Hepatitis B Virus? --- the identification of sodium taurocholate cotransporting peptide as a viral receptor,http://dx.doi.org/10.1186/2045-3701-3-2,PMC3562259,23311606,CC BY,"Following the successful cloning of receptor for SARS coronavirus a few years ago, Dr. Wenhui Li and colleagues raised attention again by publishing a possible receptor for hepatitis B virus in eLife. We will briefly review the significance of this finding and the future prospects of hepatitis B research.",2013 Jan 11,"['Chen, Pei-Jer', 'Wu, T-C']",Cell Biosci,,,True
4b92357afea168410a305eca0e593b7955f08598,PMC,Controlling epidemic spread by social distancing: Do it well or not at all,http://dx.doi.org/10.1186/1471-2458-12-679,PMC3563464,22905965,CC BY,"BACKGROUND: Existing epidemiological models have largely tended to neglect the impact of individual behaviour on the dynamics of diseases. However, awareness of the presence of illness can cause people to change their behaviour by, for example, staying at home and avoiding social contacts. Such changes can be used to control epidemics but they exact an economic cost. Our aim is to study the costs and benefits of using individual-based social distancing undertaken by healthy individuals as a form of control. METHODS: Our model is a standard SIR model superimposed on a spatial network, without and with addition of small-world interactions. Disease spread is controlled by allowing susceptible individuals to temporarily reduce their social contacts in response to the presence of infection within their local neighbourhood. We ascribe an economic cost to the loss of social contacts, and weigh this against the economic benefit gained by reducing the impact of the epidemic. We study the sensitivity of the results to two key parameters, the individuals’ attitude to risk and the size of the awareness neighbourhood. RESULTS: Depending on the characteristics of the epidemic and on the relative economic importance of making contacts versus avoiding infection, the optimal control is one of two extremes: either to adopt a highly cautious control, thereby suppressing the epidemic quickly by drastically reducing contacts as soon as disease is detected; or else to forego control and allow the epidemic to run its course. The worst outcome arises when control is attempted, but not cautiously enough to cause the epidemic to be suppressed. The next main result comes from comparing the size of the neighbourhood of which individuals are aware to that of the neighbourhood within which transmission can occur. The control works best when these sizes match and is particularly ineffective when the awareness neighbourhood is smaller than the infection neighbourhood. The results are robust with respect to inclusion of long-range, small-world links which destroy the spatial structure, regardless of whether individuals can or cannot control them. However, addition of many non-local links eventually makes control ineffective. CONCLUSIONS: These results have implications for the design of control strategies using social distancing: a control that is too weak or based upon inaccurate knowledge, may give a worse outcome than doing nothing.",2012 Aug 20,"['Maharaj, Savi', 'Kleczkowski, Adam']",BMC Public Health,,,True
05b8deee7f76cda7511eb605e2ba84a8f46bc10f,PMC,Insights into the Roles of Cyclophilin A During Influenza Virus Infection,http://dx.doi.org/10.3390/v5010182,PMC3564116,23322171,CC BY,"Cyclophilin A (CypA) is the main member of the immunophilin superfamily that has peptidyl-prolyl cis-trans isomerase activity. CypA participates in protein folding, cell signaling, inflammation and tumorigenesis. Further, CypA plays critical roles in the replication of several viruses. Upon influenza virus infection, CypA inhibits viral replication by interacting with the M1 protein. In addition, CypA is incorporated into the influenza virus virions. Finally, Cyclosporin A (CsA), the main inhibitor of CypA, inhibits influenza virus replication through CypA-dependent and -independent pathways. This review briefly summarizes recent advances in understanding the roles of CypA during influenza virus infection.",2013 Jan 15,"['Liu, Xiaoling', 'Zhao, Zhendong', 'Liu, Wenjun']",Viruses,,,True
a31ae2d95b283ef7da701d343b992b25afa779d8,PMC,Altering SARS Coronavirus Frameshift Efficiency Affects Genomic and Subgenomic RNA Production,http://dx.doi.org/10.3390/v5010279,PMC3564121,23334702,CC BY,"In previous studies, differences in the amount of genomic and subgenomic RNA produced by coronaviruses with mutations in the programmed ribosomal frameshift signal of ORF1a/b were observed. It was not clear if these differences were due to changes in genomic sequence, the protein sequence or the frequency of frameshifting. Here, viruses with synonymous codon changes are shown to produce different ratios of genomic and subgenomic RNA. These findings demonstrate that the protein sequence is not the primary cause of altered genomic and subgenomic RNA production. The synonymous codon changes affect both the structure of the frameshift signal and frameshifting efficiency. Small differences in frameshifting efficiency result in dramatic differences in genomic RNA production and TCID(50) suggesting that the frameshifting frequency must stay above a certain threshold for optimal virus production. The data suggest that either the RNA sequence or the ratio of viral proteins resulting from different levels of frameshifting affects viral replication.",2013 Jan 18,"['Plant, Ewan P.', 'Sims, Amy C.', 'Baric, Ralph S.', 'Dinman, Jonathan D.', 'Taylor, Deborah R.']",Viruses,,,True
04fa24d6f02d6b2fd44a0cb7aa2a7e7149e6cacc,PMC,Influenza A Virus Entry Inhibitors Targeting the Hemagglutinin,http://dx.doi.org/10.3390/v5010352,PMC3564125,23340380,CC BY,"Influenza A virus (IAV) has caused seasonal influenza epidemics and influenza pandemics, which resulted in serious threat to public health and socioeconomic impacts. Until now, only 5 drugs belong to two categories are used for prophylaxis and treatment of IAV infection. Hemagglutinin (HA), the envelope glycoprotein of IAV, plays a critical role in viral binding, fusion and entry. Therefore, HA is an attractive target for developing anti‑IAV drugs to block the entry step of IAV infection. Here we reviewed the recent progress in the study of conformational changes of HA during viral fusion process and the development of HA-based IAV entry inhibitors, which may provide a new choice for controlling future influenza pandemics.",2013 Jan 22,"['Yang, Jie', 'Li, Minmin', 'Shen, Xintian', 'Liu, Shuwen']",Viruses,,,True
5739f33d00bed835fb29dd26757a04faf48905a5,PMC,Reconstitution of Membrane Proteins into Model Membranes: Seeking Better Ways to Retain Protein Activities,http://dx.doi.org/10.3390/ijms14011589,PMC3565336,23344058,CC BY,"The function of any given biological membrane is determined largely by the specific set of integral membrane proteins embedded in it, and the peripheral membrane proteins attached to the membrane surface. The activity of these proteins, in turn, can be modulated by the phospholipid composition of the membrane. The reconstitution of membrane proteins into a model membrane allows investigation of individual features and activities of a given cell membrane component. However, the activity of membrane proteins is often difficult to sustain following reconstitution, since the composition of the model phospholipid bilayer differs from that of the native cell membrane. This review will discuss the reconstitution of membrane protein activities in four different types of model membrane—monolayers, supported lipid bilayers, liposomes and nanodiscs, comparing their advantages in membrane protein reconstitution. Variation in the surrounding model environments for these four different types of membrane layer can affect the three-dimensional structure of reconstituted proteins and may possibly lead to loss of the proteins activity. We also discuss examples where the same membrane proteins have been successfully reconstituted into two or more model membrane systems with comparison of the observed activity in each system. Understanding of the behavioral changes for proteins in model membrane systems after membrane reconstitution is often a prerequisite to protein research. It is essential to find better solutions for retaining membrane protein activities for measurement and characterization in vitro.",2013 Jan 14,"['Shen, Hsin-Hui', 'Lithgow, Trevor', 'Martin, Lisandra L.']",Int J Mol Sci,,,True
e005630bf0183fb7a78efa065c0c545922d27009,PMC,Generating super-shedders: co-infection increases bacterial load and egg production of a gastrointestinal helminth,http://dx.doi.org/10.1098/rsif.2012.0588,PMC3565725,23256186,CC BY,"Co-infection by multiple parasites is common within individuals. Interactions between co-infecting parasites include resource competition, direct competition and immune-mediated interactions and each are likely to alter the dynamics of single parasites. We posit that co-infection is a driver of variation in parasite establishment and growth, ultimately altering the production of parasite transmission stages. To test this hypothesis, three different treatment groups of laboratory mice were infected with the gastrointestinal helminth Heligmosomoides polygyrus, the respiratory bacterial pathogen Bordetella bronchiseptica lux(+) or co-infected with both parasites. To follow co-infection simultaneously, self-bioluminescent bacteria were used to quantify infection in vivo and in real-time, while helminth egg production was monitored in real-time using faecal samples. Co-infection resulted in high bacterial loads early in the infection (within the first 5 days) that could cause host mortality. Co-infection also produced helminth ‘super-shedders’; individuals that chronically shed the helminth eggs in larger than average numbers. Our study shows that co-infection may be one of the underlying mechanisms for the often-observed high variance in parasite load and shedding rates, and should thus be taken into consideration for disease management and control. Further, using self-bioluminescent bacterial reporters allowed quantification of the progression of infection within the whole animal of the same individuals at a fine temporal scale (daily) and significantly reduced the number of animals used (by 85%) compared with experiments that do not use in vivo techniques. Thus, we present bioluminescent imaging as a novel, non-invasive tool offering great potential to be taken forward into other applications of infectious disease ecology.",2013 Mar 6,"['Lass, Sandra', 'Hudson, Peter J.', 'Thakar, Juilee', 'Saric, Jasmina', 'Harvill, Eric', 'Albert, Réka', 'Perkins, Sarah E.']",J R Soc Interface,,,True
4fc7caae919d6b80f27561b9d034650a220affbb,PMC,Inferring population-level contact heterogeneity from common epidemic data,http://dx.doi.org/10.1098/rsif.2012.0578,PMC3565785,23034353,CC BY,"Models of infectious disease spread that incorporate contact heterogeneity through contact networks are an important tool for epidemiologists studying disease dynamics and assessing intervention strategies. One of the challenges of contact network epidemiology has been the difficulty of collecting individual and population-level data needed to develop an accurate representation of the underlying host population's contact structure. In this study, we evaluate the utility of common epidemiological measures (R(0), epidemic peak size, duration and final size) for inferring the degree of heterogeneity in a population's unobserved contact structure through a Bayesian approach. We test the method using ground truth data and find that some of these epidemiological metrics are effective at classifying contact heterogeneity. The classification is also consistent across pathogen transmission probabilities, and so can be applied even when this characteristic is unknown. In particular, the reproductive number, R(0), turns out to be a poor classifier of the degree heterogeneity, while, unexpectedly, final epidemic size is a powerful predictor of network structure across the range of heterogeneity. We also evaluate our framework on empirical epidemiological data from past and recent outbreaks to demonstrate its application in practice and to gather insights about the relevance of particular contact structures for both specific systems and general classes of infectious disease. We thus introduce a simple approach that can shed light on the unobserved connectivity of a host population given epidemic data. Our study has the potential to inform future data-collection efforts and study design by driving our understanding of germane epidemic measures, and highlights a general inferential approach to learning about host contact structure in contemporary or historic populations of humans and animals.",2013 Jan 6,"['Stack, J. Conrad', 'Bansal, Shweta', 'Kumar, V. S. Anil', 'Grenfell, Bryan']",J R Soc Interface,,,True
5b965255f0dc3c8ef81a95673bcbfe57d902010f,PMC,Clinical development of monoclonal antibody-based drugs in HIV and HCV diseases,http://dx.doi.org/10.1186/1741-7015-11-4,PMC3565905,23289632,CC BY,"Today there are many licensed antiviral drugs, but the emergence of drug resistant strains sometimes invalidates the effects of the current therapies used in the treatment of infectious diseases. Compared to conventional antiviral drugs, monoclonal antibodies (mAbs) used as pharmacological molecules have particular physical characteristics and modes of action, and, therefore, they should be considered as a distinct therapeutic class. Despite being historically validated, antibodies may represent a novel tool for combatting infectious diseases. The current high cost of mAbs' production, storage and administration (by injection only) and the consequent obstacles to development are outweighed by mAbs' clinical advantages. These are related to a low toxicity combined with high specificity and versatility, which allows a specific antibody to mediate various biological effects, ranging from the virus neutralization mechanisms to the modulation of immune responses. This review briefly summarizes the recent technological advances in the field of immunoglobulin research, and the current status of mAb-based drugs in clinical trials for HIV and HCV diseases. For each clinical trial the available data are reported and the emerging conceptual problems of the employed mAbs are highlighted. This overview helps to give a clear picture of the efficacy and challenges of the mAbs in the field of these two infectious diseases which have such a global impact.",2013 Jan 4,"['Flego, Michela', 'Ascione, Alessandro', 'Cianfriglia, Maurizio', 'Vella, Stefano']",BMC Med,,,True
60e49bb744eb678ae1ac1fb9bb920a5b01954041,PMC,An analysis of the health status of the United Arab Emirates: the ‘Big 4’ public health issues,http://dx.doi.org/10.3402/gha.v6i0.20100,PMC3566378,23394856,CC BY,"BACKGROUND: The United Arab Emirates (UAE) is a rapidly developing country composed of a multinational population with varying educational backgrounds, religious beliefs, and cultural practices, which pose a challenge for population-based public health strategies. A number of public health issues significantly contribute to morbidity and mortality in the UAE. This article summarises the findings of a panel of medical and public health specialists from UAE University and various government health agencies commissioned to report on the health status of the UAE population. METHODS: A systematic literature search was conducted to retrieve peer-reviewed articles on health in the UAE, and unpublished data were provided by government health authorities and local hospitals. RESULTS: The panel reviewed and evaluated all available evidence to list and rank (1=highest priority) the top four main public health issues: 1) Cardiovascular disease accounted for more than 25% of deaths in 2010; 2) Injury caused 17% of mortality for all age groups in 2010; 3) Cancer accounted for 10% of all deaths in 2010, and the incidence of all cancers is projected to double by 2020; and 4) Respiratory disorders were the second most common non-fatal condition in 2010. CONCLUSION: The major public health challenges posed by certain personal (e.g. ethnicity, family history), lifestyle, occupational, and environmental factors associated with the development of chronic disease are not isolated to the UAE; rather, they form part of a global health problem, which requires international collaboration and action. Future research should focus on population-based public health interventions that target the factors associated with the development of various chronic diseases.",2013 Feb 5,"['Loney, Tom', 'Aw, Tar-Ching', 'Handysides, Daniel G.', 'Ali, Raghib', 'Blair, Iain', 'Grivna, Michal', 'Shah, Syed M.', 'Sheek-Hussein, Mohamud', 'El-Sadig, Mohamed', 'Sharif, Amer A.', 'El-Obaid, Yusra']",Glob Health Action,,,True
ee48061797d29eeef5a9e606841bf8ab04b1d75b,PMC,Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo,http://dx.doi.org/10.3389/fncir.2013.00011,PMC3566411,23403489,CC BY,"Defining the connections among neurons is critical to our understanding of the structure and function of the nervous system. Recombinant viruses engineered to transmit across synapses provide a powerful approach for the dissection of neuronal circuitry in vivo. We recently demonstrated that recombinant vesicular stomatitis virus (VSV) can be endowed with anterograde or retrograde transsynaptic tracing ability by providing the virus with different glycoproteins. Here we extend the characterization of the transmission and gene expression of recombinant VSV (rVSV) with the rabies virus glycoprotein (RABV-G), and provide examples of its activity relative to the anterograde transsynaptic tracer form of rVSV. rVSV with RABV-G was found to drive strong expression of transgenes and to spread rapidly from neuron to neuron in only a retrograde manner. Depending upon how the RABV-G was delivered, VSV served as a polysynaptic or monosynaptic tracer, or was able to define projections through axonal uptake and retrograde transport. In animals co-infected with rVSV in its anterograde form, rVSV with RABV-G could be used to begin to characterize the similarities and differences in connections to different areas. rVSV with RABV-G provides a flexible, rapid, and versatile tracing tool that complements the previously described VSV-based anterograde transsynaptic tracer.",2013 Feb 7,"['Beier, Kevin T.', 'Saunders, Arpiar B.', 'Oldenburg, Ian A.', 'Sabatini, Bernardo L.', 'Cepko, Constance L.']",Front Neural Circuits,,,True
2df20f5c298fe15e93bc70a752c8566c367f0faa,PMC,Isolation of a Novel Swine Influenza Virus from Oklahoma in 2011 Which Is Distantly Related to Human Influenza C Viruses,http://dx.doi.org/10.1371/journal.ppat.1003176,PMC3567177,23408893,CC BY,"Of the Orthomyxoviridae family of viruses, only influenza A viruses are thought to exist as multiple subtypes and has non-human maintenance hosts. In April 2011, nasal swabs were collected for virus isolation from pigs exhibiting influenza-like illness. Subsequent electron microscopic, biochemical, and genetic studies identified an orthomyxovirus with seven RNA segments exhibiting approximately 50% overall amino acid identity to human influenza C virus. Based on its genetic organizational similarities to influenza C viruses this virus has been provisionally designated C/Oklahoma/1334/2011 (C/OK). Phylogenetic analysis of the predicted viral proteins found that the divergence between C/OK and human influenza C viruses was similar to that observed between influenza A and B viruses. No cross reactivity was observed between C/OK and human influenza C viruses using hemagglutination inhibition (HI) assays. Additionally, screening of pig and human serum samples found that 9.5% and 1.3%, respectively, of individuals had measurable HI antibody titers to C/OK virus. C/OK virus was able to infect both ferrets and pigs and transmit to naive animals by direct contact. Cell culture studies showed that C/OK virus displayed a broader cellular tropism than a human influenza C virus. The observed difference in cellular tropism was further supported by structural analysis showing that hemagglutinin esterase (HE) proteins between two viruses have conserved enzymatic but divergent receptor-binding sites. These results suggest that C/OK virus represents a new subtype of influenza C viruses that currently circulates in pigs that has not been recognized previously. The presence of multiple subtypes of co-circulating influenza C viruses raises the possibility of reassortment and antigenic shift as mechanisms of influenza C virus evolution.",2013 Feb 7,"['Hause, Ben M.', 'Ducatez, Mariette', 'Collin, Emily A.', 'Ran, Zhiguang', 'Liu, Runxia', 'Sheng, Zizhang', 'Armien, Anibal', 'Kaplan, Bryan', 'Chakravarty, Suvobrata', 'Hoppe, Adam D.', 'Webby, Richard J.', 'Simonson, Randy R.', 'Li, Feng']",PLoS Pathog,,,True
bcfa3dbb3fadcb51bd684e07b654328d2bf4e0db,PMC,Continuous intravenous anaesthesia with sufentanil and midazolam in medetomidine premedicated New Zealand White rabbits,http://dx.doi.org/10.1186/1746-6148-9-21,PMC3568725,23351150,CC BY,"BACKGROUND: Anaesthesia in rabbits is associated with a high mortality rate, compared to that in cats and dogs. Total intravenous anaesthesia (TIVA) with drugs that provide cardiovascular stability and are rapidly metabolised could be of benefit for use in rabbits. The aim was to evaluate cardiorespiratory effects of TIVA with sufentanil-midazolam in eight New Zealand White rabbits. Subcutaneous premedication with medetomidine (0.1 mg/kg BW) was followed by IV administration of a mixture of 2.5 μg/mL sufentanil and 0.45 mg/mL midazolam at a rate of 0.3 mL/kg BW/h for anaesthetic induction. Additionally, intravenous boluses of 0.1 mL of the mixture were administered every 20 s until the righting reflex was lost. Following endotracheal intubation, anaesthesia was maintained for 60 min with an infusion rate adjusted to supress the pedal withdrawal reflex. Air and oxygen (1:2) were delivered at 3 L/min. Physiological variables were recorded before induction and at predefined time points during and after anaesthesia. RESULTS: Righting and pedal withdrawal reflexes were lost within 3 and 5 min, respectively. Doses of sufentanil and midazolam were 0.48 μg/kg BW and 0.09 mg/kg BW for induction, and 0.72 μg/kg BW/h and 0.13 mg/kg BW/h for maintenance. Apnoea occurred in two rabbits. Induction of anaesthesia caused a significant increase in heart rate, cardiac output and arterial CO(2) partial pressure and a decrease in mean arterial pressure, respiratory rate and pH. Mean time from stopping the infusion to endotracheal extubation was 5 min, and to return of the righting reflex 7 min. Anaesthesia was characterized by induction and recovery without excitation, with muscle relaxation, and absence of the pedal withdrawal reflex. CONCLUSIONS: TIVA with sufentanil-midazolam provided smooth induction and recovery of anaesthesia in rabbits but with marked hypotension and respiratory depression, requiring mechanical ventilation. Further evaluation is needed to establish if the protocol is useful for rabbits undergoing surgery.",2013 Jan 28,"['Hedenqvist, Patricia', 'Edner, Anna', 'Fahlman, Åsa', 'Jensen-Waern, Marianne']",BMC Vet Res,,,True
1449e7aedd623536a61d71bf1505622093774208,PMC,Isolation and molecular characterization of type I and type II feline coronavirus in Malaysia,http://dx.doi.org/10.1186/1743-422X-9-278,PMC3568730,23171743,CC BY,"BACKGROUND: Feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV) are two important coronaviruses of domestic cat worldwide. Although FCoV is prevalent among cats; the fastidious nature of type I FCoV to grow on cell culture has limited further studies on tissue tropism and pathogenesis of FCoV. While several studies reported serological evidence for FCoV in Malaysia, neither the circulating FCoV isolated nor its biotypes determined. This study for the first time, describes the isolation and biotypes determination of type I and type II FCoV from naturally infected cats in Malaysia. FINDINGS: Of the total number of cats sampled, 95% (40/42) were RT-PCR positive for FCoV. Inoculation of clinical samples into Crandell feline kidney cells (CrFK), and Feline catus whole fetus-4 cells (Fcwf-4), show cytopathic effect (CPE) characterized by syncytial cells formation and later cell detachment. Differentiation of FCoV biotypes using RT-PCR assay revealed that, 97.5% and 2.5% of local isolates were type I and type II FCoV, respectively. These isolates had high sequence homology and phylogenetic similarity with several FCoV isolates from Europe, South East Asia and USA. CONCLUSIONS: This study reported the successful isolation of local type I and type II FCoV evident with formation of cytopathic effects in two types of cell cultures namely the CrFK and Fcwf-4 , where the later cells being more permissive. However, the RT-PCR assay is more sensitive in detecting the antigen in suspected samples as compared to virus isolation in cell culture. The present study indicated that type I FCoV is more prevalent among cats in Malaysia.",2012 Nov 21,"['Amer, Alazawy', 'Siti Suri, Arshad', 'Abdul Rahman, Omar', 'Mohd, Hair Bejo', 'Faruku, Bande', 'Saeed, Sharif', 'Tengku Azmi, Tengku Ibrahim']",Virol J,,,True
2d9482a26d740c255bf3108d1c628e97fae3cc7a,PMC,Complete Genome Analysis of Canine Respiratory Coronavirus,http://dx.doi.org/10.1128/genomeA.00093-12,PMC3569343,23405345,CC BY,"The canine respiratory coronavirus (CRCoV) K37 strain of the family Coronaviridae, group 2, was isolated in South Korea. Its genome was analyzed by nucleotide sequencing and was determined to have 31,029 bp. The small open reading frames situated between the spike and envelope genes of most of the CRCoV strains (except the CRCoV 4180 strain) were found to encode three nonstructural proteins (4.9 kDa, 2.7 kDa, and 12.8 kDa), while those of bovine coronavirus (BCoV) encode another three nonstructural proteins (4.9 kDa, 4.8 kDa, and 12.7 kDa) and those of a recently isolated bovine respiratory coronavirus (BRCoV) were found to encode only two nonstructural proteins (4.9 kDa and 12.7 kDa). The differences in the genes encoding these small nonstructural proteins may be associated with the emergence of highly similar viruses in different hosts.",2013 Jan 31,"['Lim, Seong-in', 'Choi, Sarah', 'Lim, Ji-Ae', 'Jeoung, Hye-Young', 'Song, Jae-Young', 'dela Pena, R. C.', 'An, Dong-Jun']",Genome Announc,,,True
782bdb3d8291de8f51c2816a707833c165c3ea35,PMC,"Genome sequences published outside of Standards in Genomic Sciences, October - November 2012",http://dx.doi.org/10.4056/sigs.3597227,PMC3569392,,CC BY,"The purpose of this table is to provide the community with a citable record of publications of ongoing genome sequencing projects that have led to a publication in the scientific literature. While our goal is to make the list complete, there is no guarantee that we may have omitted one or more publications appearing in this time frame. Readers and authors who wish to have publications added to subsequent versions of this list are invited to provide the bibliographic data for such references to the SIGS editorial office.",2012 Dec 12,"['Nelson, Oranmiyan W.', 'Garrity, George M.']",Stand Genomic Sci,,,True
9b56c6e647ccdb8b5d534c0689a71efb7728a311,PMC,Binding of DC-SIGN to the Hemagglutinin of Influenza A Viruses Supports Virus Replication in DC-SIGN Expressing Cells,http://dx.doi.org/10.1371/journal.pone.0056164,PMC3570528,23424649,CC BY,"Dendritic cells express lectins receptors, like DC-SIGN, which allow these cells to sense glycans that are present on various bacterial and viral pathogens. Interaction of DC-SIGN with carbohydrate moieties induces maturation of dendritic cells and promotes endocytosis of pathogens which is an important property of these professional antigen presenting cells. Uptake of pathogens by dendritic cells may lead to cross-presentation of antigens or infection of these cells, which ultimately results in activation of virus-specific T cells in draining lymph nodes. Little is known about the interaction of DC-SIGN with influenza A viruses. Here we show that a virus with a non-functional receptor binding site in its hemagglutinin, can replicate in cells expressing DC-SIGN. Also in the absence of sialic acids, which is the receptor for influenza A viruses, these viruses replicate in DC-SIGN expressing cells including human dendritic cells. Furthermore, the efficiency of DC-SIGN mediated infection is dependent on the extent of glycosylation of the viral hemagglutinin.",2013 Feb 12,"['Hillaire, Marine L. B.', 'Nieuwkoop, Nella J.', 'Boon, Adrianus C. M.', 'de Mutsert, Gerrie', 'Vogelzang-van Trierum, Stella E.', 'Fouchier, Ron A. M.', 'Osterhaus, Albert D. M. E.', 'Rimmelzwaan, Guus F.']",PLoS One,,,True
e172007ec7885b58e7a14be7459e0250ac47ba52,PMC,"Genome sequences published outside of Standards in Genomic Sciences, July - October 2012",http://dx.doi.org/10.4056/sigs.3416907,PMC3570808,,CC BY,"The purpose of this table is to provide the community with a citable record of publications of ongoing genome sequencing projects that have led to a publication in the scientific literature. While our goal is to make the list complete, there is no guarantee that we may have omitted one or more publications appearing in this time frame. Readers and authors who wish to have publications added to subsequent versions of this list are invited to provide the bibliographic data for such references to the SIGS editorial office.",2012 Oct 10,"['Nelson, Oranmiyan W.', 'Garrity, George M.']",Stand Genomic Sci,,,True
4f380911a4cf1b78dce1c016c1c0cc2f95a15f7b,PMC,Influenza Aerosols in UK Hospitals during the H1N1 (2009) Pandemic – The Risk of Aerosol Generation during Medical Procedures,http://dx.doi.org/10.1371/journal.pone.0056278,PMC3571988,23418548,CC BY,"BACKGROUND: Nosocomial infection of health-care workers (HCWs) during outbreaks of respiratory infections (e.g. Influenza A H1N1 (2009)) is a significant concern for public health policy makers. World Health Organization (WHO)-defined ‘aerosol generating procedures’ (AGPs) are thought to increase the risk of aerosol transmission to HCWs, but there are presently insufficient data to quantify risk accurately or establish a hierarchy of risk-prone procedures. METHODOLOGY/PRINCIPAL FINDINGS: This study measured the amount of H1N1 (2009) RNA in aerosols in the vicinity of H1N1 positive patients undergoing AGPs to help quantify the potential risk of transmission to HCWs. There were 99 sampling occasions (windows) producing a total of 198 May stages for analysis in the size ranges 0.86–7.3 µm. Considering stages 2 (4–7.3 µm) and 3 (0.86–4 µm) as comprising one sample, viral RNA was detected in 14 (14.1%) air samples from 10 (25.6%) patients. Twenty three air samples were collected while potential AGPs were being performed of which 6 (26.1%) contained viral RNA; in contrast, 76 May samples were collected when no WHO 2009 defined AGP was being performed of which 8 (10.5%) contained viral RNA (unadjusted OR = 2.84 (95% CI 1.11–7.24) adjusted OR = 4.31 (0.83–22.5)). CONCLUSIONS/SIGNIFICANCE: With our small sample size we found that AGPs do not significantly increase the probability of sampling an H1N1 (2009) positive aerosol (OR (95% CI) = 4.31 (0.83–22.5). Although the probability of detecting positive H1N1 (2009) positive aerosols when performing various AGPs on intensive care patients above the baseline rate (i.e. in the absence of AGPs) did not reach significance, there was a trend towards hierarchy of AGPs, placing bronchoscopy and respiratory and airway suctioning above baseline (background) values. Further, larger studies are required but these preliminary findings may be of benefit to infection control teams.",2013 Feb 13,"['Thompson, Katy-Anne', 'Pappachan, John V.', 'Bennett, Allan M.', 'Mittal, Himanshu', 'Macken, Susan', 'Dove, Brian K.', 'Nguyen-Van-Tam, Jonathan S.', 'Copley, Vicky R.', 'O’Brien, Sarah', 'Hoffman, Peter', 'Parks, Simon', 'Bentley, Andrew', 'Isalska, Barbara', 'Thomson, Gail', None]",PLoS One,,,True
1bebd833b3535712b5d13f9ed985e3491d3c96c8,PMC,Chloroquine Inhibits Dengue Virus Type 2 Replication in Vero Cells but Not in C6/36 Cells,http://dx.doi.org/10.1155/2013/282734,PMC3572654,23431254,CC BY,"Dengue viruses are the most important arthropod-borne viruses in terms of morbidity and mortality in the world. Since there is no dengue vaccine available for human use, we have set out to investigate the use of chloroquine as an antiviral drug against dengue. Chloroquine, an amine acidotropic drug known to affect intracellular exocytic pathways by increasing endosomal pH, was used in the in vitro treatment of Vero and C6/36 cells infected with dengue virus type 2 (DENV-2). Real-time RT-PCR and plaque assays were used to quantify the DENV-2 load in infected Vero and C6/36 cells after chloroquine treatment. Our results showed that a dose of 50 μg/ml of chloroquine was not toxic to the cells and induced a statistically significant inhibition of virus production in infected Vero cells when compared to untreated cells. In C6/36 cells, chloroquine does not induce a statistically significant difference in viral replication when compared to untreated cells, showing that this virus uses an unlikely pathway of penetration in these cells, and results were also confirmed by the plaque assay (PFU). These data suggest that the inhibition of virus infection induced by chloroquine is due to interference with acidic vesicles in mammalian cells.",2013 Jan 31,"['Farias, Kleber Juvenal Silva', 'Machado, Paula Renata Lima', 'da Fonseca, Benedito Antônio Lopes']",ScientificWorldJournal,,,True
da284bc0d5d74602b201a169fb7a0392eef5b6f8,PMC,A novel double antibody sandwich-lateral flow immunoassay for the rapid and simple detection of hepatitis C virus,http://dx.doi.org/10.3892/ijmm.2012.1121,PMC3573733,22960954,CC BY,"The objective of this study was to screen for antigens of the hepatitis C virus (HCV) to establish a new double antibody sandwich-lateral flow immunoassay (DAS-LFIA) method for testing the presence of anti-HCV antibodies in human serum or plasma. A series of different recombinant HCV proteins in Escherichia coli cells were constructed, expressed, purified and the new DAS-LFIA strip was developed. The sensitivity and specificity of new the DAS-LFIA strip were evaluated by detecting 23 HCV-positive sera, a set of quality control references for anti-HCV detection that contain known amounts of anti-HCV antibodies, and 8 HCV-negative sera. A total of 300 clinical serum samples was examined by both the new DAS-LFIA strip and enzyme-linked immunosorbent assay (ELISA). Data were analyzed using SPSS 11.5 software. The sensitivity and specificity of the new DAS-LFIA strip were 100%. The lowest test line of the HCV DAS-LFIA strips was 2 NCU/ml. Additionally, the concordance between the new DAS-LFIA strip and ELISA methods was 94.33%. In conclusion, our new testing method is rapid, simple, sensitive and specifically detects the presence of anti-HCV antibodies in human serum or plasma. Therefore, it may be used for monitoring HCV.",2012 Nov 6,"['XIANG, TINGXIU', 'JIANG, ZHENG', 'ZHENG, JIAN', 'LO, CHAOYU', 'TSOU, HARRY', 'REN, GUOSHENG', 'ZHANG, JUN', 'HUANG, AILONG', 'LAI, GUOQI']",Int J Mol Med,,,True
70fefc54856d09f01cb983932a860dc4dacb9f46,PMC,Curcumin inhibits HCV replication by induction of heme oxygenase-1 and suppression of AKT,http://dx.doi.org/10.3892/ijmm.2012.1096,PMC3573749,22922731,CC BY,"Although hepatitis C virus (HCV) affects approximately 130–170 million people worldwide, no vaccines are available. HCV is an important cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, leading to the need for liver transplantation. In this study, curcumin, a constituent used in traditional Chinese medicine, has been evaluated for its anti-HCV activity and mechanism, using a human hepatoma cell line containing the HCV genotype 1b subgenomic replicon. Below the concentration of 20% cytotoxicity, curcumin dose-dependently inhibited HCV replication by luciferase reporter gene assay, HCV RNA detection and HCV protein analysis. Under the same conditions, curcumin also dose-dependently induced heme oxygenase-1 with the highest induction at 24 h. Hemin, a heme oxygenase-1 inducer, also inhibited HCV protein expression in a dose-dependent manner. The knockdown of heme oxygenase-1 partially reversed the curcumin-inhibited HCV protein expression. In addition to the heme oxygenase-1 induction, signaling molecule activities of AKT, extracellular signal-regulated kinases (ERK) and nuclear factor-κB (NF-κB) were inhibited by curcumin. Using specific inhibitors of PI3K-AKT, MEK-ERK and NF-κB, the results suggested that only PI3K-AKT inhibition is positively involved in curcumin-inhibited HCV replication. Inhibition of ERK and NF-κB was likely to promote HCV protein expression. In summary, curcumin inhibited HCV replication by heme oxygenase-1 induction and AKT pathway inhibition. Although curcumin also inhibits ERK and NF-κB activities, it slightly increased the HCV protein expression. This result may provide information when curcumin is used as an adjuvant in anti-HCV therapy.",2012 Nov 20,"['CHEN, MING-HO', 'LEE, MING-YANG', 'CHUANG, JING-JING', 'LI, YI-ZHEN', 'NING, SIN-TZU', 'CHEN, JUNG-CHOU', 'LIU, YI-WEN']",Int J Mol Med,,,True
a63e10c460821fd20aa9f58b6d7f4634b05b16ce,PMC,The role of infections and coinfections with newly identified and emerging respiratory viruses in children,http://dx.doi.org/10.1186/1743-422X-9-247,PMC3573994,23102237,CC BY,"Acute respiratory infections are a major cause of morbidity in children both in developed and developing countries. A wide range of respiratory viruses, including respiratory syncytial virus (RSV), influenza A and B viruses, parainfluenza viruses (PIVs), adenovirus, rhinovirus (HRV), have repeatedly been detected in acute lower respiratory tract infections (LRTI) in children in the past decades. However, in the last ten years thanks to progress in molecular technologies, newly discovered viruses have been identified including human Metapneumovirus (hMPV), coronaviruses NL63 (HcoV-NL63) and HKU1 (HcoV-HKU1), human Bocavirus (HBoV), new enterovirus (HEV), parechovirus (HpeV) and rhinovirus (HRV) strains, polyomaviruses WU (WUPyV) and KI (KIPyV) and the pandemic H1N1v influenza A virus. These discoveries have heavily modified previous knowledge on respiratory infections mainly highlighting that pediatric population is exposed to a variety of viruses with similar seasonal patterns. In this context establishing a causal link between a newly identified virus and the disease as well as an association between mixed infections and an increase in disease severity can be challenging. This review will present an overview of newly recognized as well as the main emerging respiratory viruses and seek to focus on the their contribution to infection and co-infection in LRTIs in childhood.",2012 Oct 27,"['Debiaggi, Maurizia', 'Canducci, Filippo', 'Ceresola, Elisa Rita', 'Clementi, Massimo']",Virol J,,,True
e05c7165987a9b706d1ab55ebb210bd571a59e5a,PMC,Discovery and antitumor activities of constituents from Cyrtomium fortumei (J.) Smith rhizomes,http://dx.doi.org/10.1186/1752-153X-7-24,PMC3574041,23379693,CC BY,"BACKGROUND: Cyrtomium fortumei (J.) Smith is an important Chinese herbal medicine because of its biological functions. However, systematic and comprehensive studies on the phytochemicals from Cyrtomium fortumei (J.) Smith and their bioactivity are limited. RESULTS: Using the bioassay-guided technique, the ethyl acetate and n-BuOH extracts of the rhizomes of Cyrtomium fortumei (J.) Smith were shown to exhibit good antitumor activities, consequently leading to the isolation of 23 compounds. All compounds were isolated from the plant for the first time. The inhibitory activities of these compounds were investigated on tumor cells MGC-803, PC3, and A375 in vitro by MTT (thiazolyl blue tetrazolium bromide) assay, and the results showed that pimpinellin (3) had potent cytotoxic activities against the three cell lines, with the IC(50) values of 14.4 ± 0.3 μM, 20.4 ± 0.5 μM, and 29.2 ± 0.6 μM, respectively. The mechanism of the antitumor action indicated that pimpinellin inhibited the growth of MGC-803 cells via the induction of tumor cell apoptosis, with apoptosis ratio of 27.44% after 72 h of treatment at 20 μM. CONCLUSIONS: This study suggests that most of the compounds from the roots of Cyrtomium fortumei (J.) Smith could inhibit the growth of human carcinoma cells. Moreover, pimpinellin inhibited the growth of tumor cells via the induction of tumor cell apoptosis.",2013 Feb 4,"['Yang, Shengjie', 'Liu, Mingchuan', 'Liang, Na', 'Zhao, Qi', 'Zhang, Yuping', 'Xue, Wei', 'Yang, Song']",Chem Cent J,,,True
4152ae12ac49d157a290281842bce9e9d16096a7,PMC,Residue analysis of a CTL epitope of SARS-CoV spike protein by IFN-gamma production and bioinformatics prediction,http://dx.doi.org/10.1186/1471-2172-13-50,PMC3575293,22963340,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by the novel coronavirus SARS-CoV. The T cell epitopes of the SARS CoV spike protein are well known, but no systematic evaluation of the functional and structural roles of each residue has been reported for these antigenic epitopes. Analysis of the functional importance of side-chains by mutational study may exaggerate the effect by imposing a structural disturbance or an unusual steric, electrostatic or hydrophobic interaction. RESULTS: We demonstrated that N50 could induce significant IFN-gamma response from SARS-CoV S DNA immunized mice splenocytes by the means of ELISA, ELISPOT and FACS. Moreover, S366-374 was predicted to be an optimal epitope by bioinformatics tools: ANN, SMM, ARB and BIMAS, and confirmed by IFN-gamma response induced by a series of S358-374-derived peptides. Furthermore, each of S366-374 was replaced by alanine (A), lysine (K) or aspartic acid (D), respectively. ANN was used to estimate the binding affinity of single S366-374 mutants to H-2 Kd. Y367 and L374 were predicated to possess the most important role in peptide binding. Additionally, these one residue mutated peptides were synthesized, and IFN-gamma production induced by G368, V369, A371, T372 and K373 mutated S366-374 were decreased obviously. CONCLUSIONS: We demonstrated that S366-374 is an optimal H-2 Kd CTL epitope in the SARS CoV S protein. Moreover, Y367, S370, and L374 are anchors in the epitope, while C366, G368, V369, A371, T372, and K373 may directly interact with TCR on the surface of CD8-T cells.",2012 Sep 10,"['Huang, Jun', 'Cao, Yingnan', 'Bu, Xianzhang', 'Wu, Changyou']",BMC Immunol,,,True
ae79fbbd7e6130c0d5b451617260a7e63bda79e4,PMC,Lessons learned from a double-blind randomised placebo-controlled study with a iota-carrageenan nasal spray as medical device in children with acute symptoms of common cold,http://dx.doi.org/10.1186/1472-6882-12-147,PMC3575307,22950667,CC BY,"BACKGROUND: Common cold is caused by a variety of respiratory viruses. The prevalence in children is high, and it potentially contributes to significant morbidity. Iota-carragenan, a polymer derived from red seaweed, has reduced viral load in nasal secretions and alleviated symptoms in adults with common cold. METHODS: We have assessed the antiviral and therapeutic activity of a nasal spray containing iota-carrageenan in children with acute symptoms of common cold. A cohort of 153 children between 1–18 years (mean age 5 years), displaying acute symptoms of common cold were randomly assigned to treatment with a nasal spray containing iota-carrageenan (0.12%) as verum or 0.9% sodium chloride solution as placebo for seven days. Symptoms of common cold were recorded and the viral load of respiratory viruses in nasal secretions was determined at two consecutive visits. RESULTS: The results of the present study showed no significant difference between the iota carrageenan and the placebo group on the mean of TSS between study days 2–7. Secondary endpoints, such as reduced time to clearance of disease (7.6 vs 9.4 days; p = 0.038), reduction of viral load (p = 0.026), and lower incidence of secondary infections with other respiratory viruses (p = 0.046) indicated beneficial effects of iota-carrageenan in this population. The treatment was safe and well tolerated, with less side effects observed in the verum group compared to placebo. CONCLUSION: In this study iota-carrageenan did not alleviate symptoms in children with acute symptoms of common cold, but significantly reduced viral load in nasal secretions that may have important implications for future studies. TRIAL REGISTRATION: ISRCTN52519535, http://www.controlled-trials.com/ISRCTN52519535/",2012 Sep 5,"['Fazekas, Tamas', 'Eickhoff, Philipp', 'Pruckner, Nathalie', 'Vollnhofer, Georg', 'Fischmeister, Gustav', 'Diakos, Christopher', 'Rauch, Margit', 'Verdianz, Maria', 'Zoubek, Andreas', 'Gadner, Helmut', 'Lion, Thomas']",BMC Complement Altern Med,,,True
1e863993819f87abe5cee255ccb97d623838542a,PMC,A novel bocavirus in canine liver,http://dx.doi.org/10.1186/1743-422X-10-54,PMC3577433,23402347,CC BY,"BACKGROUND: Bocaviruses are classified as a genus within the Parvoviridae family of single-stranded DNA viruses and are pathogenic in some mammalian species. Two species have been previously reported in dogs, minute virus of canines (MVC), associated with neonatal diseases and fertility disorders; and Canine bocavirus (CBoV), associated with respiratory disease. FINDINGS: In this study using deep sequencing of enriched viral particles from the liver of a dog with severe hemorrhagic gastroenteritis, necrotizing vasculitis, granulomatous lymphadenitis and anuric renal failure, we identified and characterized a novel bocavirus we named Canine bocavirus 3 (CnBoV3). The three major ORFs of CnBoV3 (NS1, NP1 and VP1) shared less than 60% aa identity with those of other bocaviruses qualifying it as a novel species based on ICTV criteria. Inverse PCR showed the presence of concatemerized or circular forms of the genome in liver. CONCLUSIONS: We genetically characterized a bocavirus in a dog liver that is highly distinct from prior canine bocaviruses found in respiratory and fecal samples. Its role in this animal’s complex disease remains to be determined.",2013 Feb 13,"['Li, Linlin', 'Pesavento, Patricia A', 'Leutenegger, Christian M', 'Estrada, Marko', 'Coffey, Lark L', 'Naccache, Samia N', 'Samayoa, Erik', 'Chiu, Charles', 'Qiu, Jianming', 'Wang, Chunlin', 'Deng, Xutao', 'Delwart, Eric']",Virol J,,,True
e3090e4e8baa6df559f0299519ad77821a09f873,PMC,"Modeling the impact of air, sea, and land travel restrictions supplemented by other interventions on the emergence of a new influenza pandemic virus",http://dx.doi.org/10.1186/1471-2334-12-309,PMC3577649,23157818,CC BY,"BACKGROUND: During the early stages of a new influenza pandemic, travel restriction is an immediate and non-pharmaceutical means of retarding incidence growth. It extends the time frame of effective mitigation, especially when the characteristics of the emerging virus are unknown. In the present study, we used the 2009 influenza A pandemic as a case study to evaluate the impact of regulating air, sea, and land transport. Other government strategies, namely, antivirals and hospitalizations, were also evaluated. METHODS: Hong Kong arrivals from 44 countries via air, sea, and land transports were imported into a discrete stochastic Susceptible, Exposed, Infectious and Recovered (SEIR) host-flow model. The model allowed a number of latent and infectious cases to pass the border, which constitutes a source of local disease transmission. We also modeled antiviral and hospitalization prevention strategies to compare the effectiveness of these control measures. Baseline reproduction rate was estimated from routine surveillance data. RESULTS: Regarding air travel, the main route connected to the influenza source area should be targeted for travel restrictions; imposing a 99% air travel restriction delayed the epidemic peak by up to two weeks. Once the pandemic was established in China, the strong land connection between Hong Kong and China rendered Hong Kong vulnerable. Antivirals and hospitalization were found to be more effective on attack rate reductions than travel restrictions. Combined strategies (with 99% restriction on all transport modes) deferred the peak for long enough to establish a vaccination program. CONCLUSION: The findings will assist policy-makers with decisions on handling similar future pandemics. We also suggest regulating the extent of restriction and the transport mode, once restriction has been deemed necessary for pandemic control. Although travel restrictions have yet to gain social acceptance, they allow time for mitigation response when a new and highly intrusive virus emerges.",2012 Nov 19,"['Chong, Ka Chun', 'Ying Zee, Benny Chung']",BMC Infect Dis,,,True
9b4d56c6c289c7f86b4f01b1b5569ae7e2bf6920,PMC,"Modeling the impact of air, sea, and land travel restrictions supplemented by other interventions on the emergence of a new influenza pandemic virus",http://dx.doi.org/10.1186/1471-2334-12-309,PMC3577649,23157818,CC BY,"BACKGROUND: During the early stages of a new influenza pandemic, travel restriction is an immediate and non-pharmaceutical means of retarding incidence growth. It extends the time frame of effective mitigation, especially when the characteristics of the emerging virus are unknown. In the present study, we used the 2009 influenza A pandemic as a case study to evaluate the impact of regulating air, sea, and land transport. Other government strategies, namely, antivirals and hospitalizations, were also evaluated. METHODS: Hong Kong arrivals from 44 countries via air, sea, and land transports were imported into a discrete stochastic Susceptible, Exposed, Infectious and Recovered (SEIR) host-flow model. The model allowed a number of latent and infectious cases to pass the border, which constitutes a source of local disease transmission. We also modeled antiviral and hospitalization prevention strategies to compare the effectiveness of these control measures. Baseline reproduction rate was estimated from routine surveillance data. RESULTS: Regarding air travel, the main route connected to the influenza source area should be targeted for travel restrictions; imposing a 99% air travel restriction delayed the epidemic peak by up to two weeks. Once the pandemic was established in China, the strong land connection between Hong Kong and China rendered Hong Kong vulnerable. Antivirals and hospitalization were found to be more effective on attack rate reductions than travel restrictions. Combined strategies (with 99% restriction on all transport modes) deferred the peak for long enough to establish a vaccination program. CONCLUSION: The findings will assist policy-makers with decisions on handling similar future pandemics. We also suggest regulating the extent of restriction and the transport mode, once restriction has been deemed necessary for pandemic control. Although travel restrictions have yet to gain social acceptance, they allow time for mitigation response when a new and highly intrusive virus emerges.",2012 Nov 19,"['Chong, Ka Chun', 'Ying Zee, Benny Chung']",BMC Infect Dis,,,True
db5d4d312d002e6bdc87f433d1ad118681167016,PMC,Detection of infectious bronchitis virus serotypes by reverse transcription polymerase chain reaction in broiler chickens,http://dx.doi.org/10.1186/2193-1801-2-36,PMC3579474,23450039,CC BY,"Infectious bronchitis (IB) is a highly contagious disease of the respiratory and urogenital tract of chickens, caused by infectious bronchitis virus (IBV), a member of the family Coronaviridae. The disease is common throughout the world where chickens are produced commercially. PCR on reverse transcribed RNA is a potent technique for the detection of IBV. In comparison with classical detection methods, PCR-based techniques are both sensitive and fast. Dozens of serotypes and genotypes of IBV have been detected, and many more will surely be reported in future. This research was conducted to identify the infectious bronchitis virus with group specific primers of avian Coronaviruses in Zabol, southeast of Iran. Tracheal swabs were collected from eleven commercial broiler flocks and these swabs were used for RNA extraction. General primers included XCE2+ and XCE2- that amplify all IBV serotypes were used. Primers MCE1+, BCE1+ and DCE1+ was used to amplifying the specific nucleotide sequence of Massachusetts, 4/91 and D274 serotypes, respectively. The results of this study showed that 36.36% of the sampled flocks were positive to IBV by RT-PCR. Moreover, the Massachusetts was the identified serotype of infectious bronchitis virus. The results provide the first molecular evidence for the presence of infectious bronchitis virus and Massachusetts serotype in Zabol. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-36) contains supplementary material, which is available to authorized users.",2013 Jan 31,"['Jahantigh, Mohammad', 'Salari, Saeed', 'Hedayati, Mahdi']",Springerplus,,,True
b293146d54c66eef361bc16cc69f793f46f88f1b,PMC,Tracking and visualization of space-time activities for a micro-scale flu transmission study,http://dx.doi.org/10.1186/1476-072X-12-6,PMC3579692,23388060,CC BY,"BACKGROUND: Infectious diseases pose increasing threats to public health with increasing population density and more and more sophisticated social networks. While efforts continue in studying the large scale dissemination of contagious diseases, individual-based activity and behaviour study benefits not only disease transmission modelling but also the control, containment, and prevention decision making at the local scale. The potential for using tracking technologies to capture detailed space-time trajectories and model individual behaviour is increasing rapidly, as technological advances enable the manufacture of small, lightweight, highly sensitive, and affordable receivers and the routine use of location-aware devices has become widespread (e.g., smart cellular phones). The use of low-cost tracking devices in medical research has also been proved effective by more and more studies. This study describes the use of tracking devices to collect data of space-time trajectories and the spatiotemporal processing of such data to facilitate micro-scale flu transmission study. We also reports preliminary findings on activity patterns related to chances of influenza infection in a pilot study. METHODS: Specifically, this study employed A-GPS tracking devices to collect data on a university campus. Spatiotemporal processing was conducted for data cleaning and segmentation. Processed data was validated with traditional activity diaries. The A-GPS data set was then used for visual explorations including density surface visualization and connection analysis to examine space-time activity patterns in relation to chances of influenza infection. RESULTS: When compared to diary data, the segmented tracking data demonstrated to be an effective alternative and showed greater accuracies in time as well as the details of routes taken by participants. A comparison of space-time activity patterns between participants who caught seasonal influenza and those who did not revealed interesting patterns. CONCLUSIONS: This study proved that tracking technology an effective technique for obtaining data for micro-scale influenza transmission research. The findings revealed micro-scale transmission hotspots on a university campus and provided insights for local control and prevention strategies.",2013 Feb 7,"['Qi, Feng', 'Du, Fei']",Int J Health Geogr,,,True
426d73371e7f29a3d046687525d416f68708f643,PMC,Persistent digestive disorders in the tropics: causative infectious pathogens and reference diagnostic tests,http://dx.doi.org/10.1186/1471-2334-13-37,PMC3579720,23347408,CC BY,"BACKGROUND: Persistent digestive disorders account for considerable disease burden in the tropics. Despite advances in understanding acute gastrointestinal infections, important issues concerning epidemiology, diagnosis, treatment and control of most persistent digestive symptomatologies remain to be elucidated. Helminths and intestinal protozoa are considered to play major roles, but the full extent of the aetiologic spectrum is still unclear. We provide an overview of pathogens causing digestive disorders in the tropics and evaluate available reference tests. METHODS: We searched the literature to identify pathogens that might give rise to persistent diarrhoea, chronic abdominal pain and/or blood in the stool. We reviewed existing laboratory diagnostic methods for each pathogen and stratified them by (i) microscopy; (ii) culture techniques; (iii) immunological tests; and (iv) molecular methods. Pathogen-specific reference tests providing highest diagnostic accuracy are described in greater detail. RESULTS: Over 30 pathogens may cause persistent digestive disorders. Bacteria, viruses and parasites are important aetiologic agents of acute and long-lasting symptomatologies. An integrated approach, consisting of stool culture, microscopy and/or specific immunological techniques for toxin, antigen and antibody detection, is required for accurate diagnosis of bacteria and parasites. Molecular techniques are essential for sensitive diagnosis of many viruses, bacteria and intestinal protozoa, and are increasingly utilised as adjuncts for helminth identification. CONCLUSIONS: Diagnosis of the broad spectrum of intestinal pathogens is often cumbersome. There is a need for rapid diagnostic tests that are simple and affordable for resource-constrained settings, so that the management of patients suffering from persistent digestive disorders can be improved.",2013 Jan 24,"['Becker, Sören L', 'Vogt, Jürg', 'Knopp, Stefanie', 'Panning, Marcus', 'Warhurst, David C', 'Polman, Katja', 'Marti, Hanspeter', 'von Müller, Lutz', 'Yansouni, Cedric P', 'Jacobs, Jan', 'Bottieau, Emmanuel', 'Sacko, Moussa', 'Rijal, Suman', 'Meyanti, Fransiska', 'Miles, Michael A', 'Boelaert, Marleen', 'Lutumba, Pascal', 'van Lieshout, Lisette', 'N’Goran, Eliézer K', 'Chappuis, François', 'Utzinger, Jürg']",BMC Infect Dis,,,True
0414c8763c6ec295be60d86698ec3a76e981e54f,PMC,Synthetic Genomics and Synthetic Biology Applications Between Hopes and Concerns,http://dx.doi.org/10.2174/1389202911314010003,PMC3580775,23997647,CC BY,"New organisms and biological systems designed to satisfy human needs are among the aims of synthetic genomics and synthetic biology. Synthetic biology seeks to model and construct biological components, functions and organisms that do not exist in nature or to redesign existing biological systems to perform new functions. Synthetic genomics, on the other hand, encompasses technologies for the generation of chemically-synthesized whole genomes or larger parts of genomes, allowing to simultaneously engineer a myriad of changes to the genetic material of organisms. Engineering complex functions or new organisms in synthetic biology are thus progressively becoming dependent on and converging with synthetic genomics. While applications from both areas have been predicted to offer great benefits by making possible new drugs, renewable chemicals or clean energy, they have also given rise to concerns about new safety, environmental and socio-economic risks – stirring an increasingly polarizing debate. Here we intend to provide an overview on recent progress in biomedical and biotechnological applications of synthetic genomics and synthetic biology as well as on arguments and evidence related to their possible benefits, risks and governance implications.",2013 Mar,"['König, Harald', 'Frank, Daniel', 'Heil, Reinhard', 'Coenen, Christopher']",Curr Genomics,,,True
a33e3ade1bf2a47195051d6d458baa2001ab72a5,PMC,Prescription Surveillance and Polymerase Chain Reaction Testing to Identify Pathogens during Outbreaks of Infection,http://dx.doi.org/10.1155/2013/746053,PMC3581269,23509772,CC BY,"Syndromic surveillance, including prescription surveillance, offers a rapid method for the early detection of agents of bioterrorism and emerging infectious diseases. However, it has the disadvantage of not considering definitive diagnoses. Here, we attempted to definitively diagnose pathogens using polymerase chain reaction (PCR) immediately after the prescription surveillance system detected an outbreak. Specimens were collected from 50 patients with respiratory infections. PCR was used to identify the pathogens, which included 14 types of common respiratory viruses and Mycoplasma pneumoniae. Infectious agents including M. pneumoniae, respiratory syncytial virus (RSV), rhinovirus, enterovirus, and parainfluenza virus were detected in 54% of patients. For the rapid RSV diagnosis kit, sensitivity was 80% and specificity was 85%. For the rapid adenovirus diagnosis kit, no positive results were obtained; therefore, sensitivity could not be calculated and specificity was 100%. Many patients were found to be treated for upper respiratory tract infections without the diagnosis of a specific pathogen. In Japan, an outbreak of M. pneumoniae infection began in 2011, and our results suggested that this outbreak may have included false-positive cases. By combining syndromic surveillance and PCR, we were able to rapidly and accurately identify causative pathogens during a recent respiratory infection outbreak.",2013 Feb 7,"['Sugiura, Hiroaki', 'Fujimoto, Tsuguto', 'Sugawara, Tamie', 'Hanaoka, Nozomu', 'Konagaya, Masami', 'Kikuchi, Kiyoshi', 'Hanada, Eisuke', 'Okabe, Nobuhiko', 'Ohkusa, Yasushi']",Biomed Res Int,,,True
ff76f00bf68006acc97c8720dd4f11e69d17c272,PMC,Glucocorticosteroids as Dengue Therapeutics: Resolving Clinical Observations With a Primary Human Macrophage Model,http://dx.doi.org/10.1093/cid/cis1048,PMC3582356,23243185,CC BY,,2013 Mar 15,"['Sayce, Andrew C.', 'Miller, Joanna L.', 'Zitzmann, Nicole']",Clin Infect Dis,,,True
3d3886831b542dfc9d1b6428ac48d96589d0ae61,PMC,The R0 package: a toolbox to estimate reproduction numbers for epidemic outbreaks,http://dx.doi.org/10.1186/1472-6947-12-147,PMC3582628,23249562,CC BY,"BACKGROUND: Several generic methods have been proposed to estimate transmission parameters during an outbreak, especially the reproduction number. However, as of today, no dedicated software exists that implements these methods and allow comparisons. RESULTS: A review of generic methods used to estimate transmissibility parameters during outbreaks was carried out. Most methods used the epidemic curve and the generation time distribution. Two categories of methods were available: those estimating the initial reproduction number, and those estimating a time dependent reproduction number. We implemented five methods as an R library, developed sensitivity analysis tools for each method and provided numerical illustrations of their use. A comparison of the performance of the different methods on simulated datasets is reported. CONCLUSIONS: This software package allows a standardized and extensible approach to the estimation of the reproduction number and generation interval distribution from epidemic curves.",2012 Dec 18,"['Obadia, Thomas', 'Haneef, Romana', 'Boëlle, Pierre-Yves']",BMC Med Inform Decis Mak,,,True
dc352893117f666477e7cf7c8c614bdf60592178,PMC,Enhancing Bioaerosol Sampling by Andersen Impactors Using Mineral-Oil-Spread Agar Plate,http://dx.doi.org/10.1371/journal.pone.0056896,PMC3584084,23460818,CC BY,"As a bioaerosol sampling standard, Andersen type impactor is widely used since its invention in 1950s, including the investigation of the anthrax attacks in the United States in 2001. However, its related problems such as impaction and desiccation stress as well as particle bounce have not been solved. Here, we improved its biological collection efficiencies by plating a mineral oil layer (100 µL) onto the agar plate. An Andersen six-stage sampler and a BioStage impactor were tested with mineral-oil-spread agar plates in collecting indoor and outdoor bacterial and fungal aerosols. The effects of sampling times (5, 10 and 20 min) were also studied using the BioStage impactor when sampling environmental bioaerosols as well as aerosolized Bacillus subtilis (G+) and Escherichia coli (G-). In addition, particle bounce reduction by mineral-oil-plate was also investigated using an optical particle counter (OPC). Experimental results revealed that use of mineral-oil-spread agar plate can substantially enhance culturable bioaerosol recoveries by Andersen type impactors (p-values<0.05). The recovery enhancement was shown to depend on bioaerosol size, type, sampling time and environment. In general, more enhancements (extra 20%) were observed for last stage of the Andersen six-stage samplers compared to the BioStage impactor for 10 min sampling. When sampling aerosolized B. subtilis, E. coli and environmental aerosols, the enhancement was shown to increase with increasing sampling time, ranging from 50% increase at 5 min to ∼100% at 20 min. OPC results indicated that use of mineral oil can effectively reduce the particle bounce with an average of 66% for 10 min sampling. Our work suggests that enhancements for fungal aerosols were primarily attributed to the reduced impaction stress, while for bacterial aerosols reduced impaction, desiccation and particle bounce played major roles. The developed technology can readily enhance the agar-based techniques including those high volume portable samplers for bioaerosol monitoring.",2013 Feb 27,"['Xu, Zhenqiang', 'Wei, Kai', 'Wu, Yan', 'Shen, Fangxia', 'Chen, Qi', 'Li, Mingzhen', 'Yao, Maosheng']",PLoS One,,,True
ebb05424e38f5e17460ce65e2ccd5a7ad4f73b42,PMC,Estimation of the National Disease Burden of Influenza-Associated Severe Acute Respiratory Illness in Kenya and Guatemala: A Novel Methodology,http://dx.doi.org/10.1371/journal.pone.0056882,PMC3584100,23573177,CC0,"BACKGROUND: Knowing the national disease burden of severe influenza in low-income countries can inform policy decisions around influenza treatment and prevention. We present a novel methodology using locally generated data for estimating this burden. METHODS AND FINDINGS: This method begins with calculating the hospitalized severe acute respiratory illness (SARI) incidence for children <5 years old and persons ≥5 years old from population-based surveillance in one province. This base rate of SARI is then adjusted for each province based on the prevalence of risk factors and healthcare-seeking behavior. The percentage of SARI with influenza virus detected is determined from provincial-level sentinel surveillance and applied to the adjusted provincial rates of hospitalized SARI. Healthcare-seeking data from healthcare utilization surveys is used to estimate non-hospitalized influenza-associated SARI. Rates of hospitalized and non-hospitalized influenza-associated SARI are applied to census data to calculate the national number of cases. The method was field-tested in Kenya, and validated in Guatemala, using data from August 2009–July 2011. In Kenya (2009 population 38.6 million persons), the annual number of hospitalized influenza-associated SARI cases ranged from 17,129–27,659 for children <5 years old (2.9–4.7 per 1,000 persons) and 6,882–7,836 for persons ≥5 years old (0.21–0.24 per 1,000 persons), depending on year and base rate used. In Guatemala (2011 population 14.7 million persons), the annual number of hospitalized cases of influenza-associated pneumonia ranged from 1,065–2,259 (0.5–1.0 per 1,000 persons) among children <5 years old and 779–2,252 cases (0.1–0.2 per 1,000 persons) for persons ≥5 years old, depending on year and base rate used. In both countries, the number of non-hospitalized influenza-associated cases was several-fold higher than the hospitalized cases. CONCLUSIONS: Influenza virus was associated with a substantial amount of severe disease in Kenya and Guatemala. This method can be performed in most low and lower-middle income countries.",2013 Feb 27,"['Fuller, James A.', 'Summers, Aimee', 'Katz, Mark A.', 'Lindblade, Kim A.', 'Njuguna, Henry', 'Arvelo, Wences', 'Khagayi, Sammy', 'Emukule, Gideon', 'Linares-Perez, Nivaldo', 'McCracken, John', 'Nokes, D. James', 'Ngama, Mwanajuma', 'Kazungu, Sidi', 'Mott, Joshua A.', 'Olsen, Sonja J.', 'Widdowson, Marc-Alain', 'Feikin, Daniel R.']",PLoS One,,,True
63cfec0de40f78765303a3fd6f853c672a193320,PMC,Humoral immune response to HTLV-1 basic leucine zipper factor (HBZ) in HTLV-1-infected individuals,http://dx.doi.org/10.1186/1742-4690-10-19,PMC3584941,23405908,CC BY,"BACKGROUND: Human T cell lymphotropic virus type 1 (HTLV-1) infection can lead to development of adult T cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a subset of infected subjects. HTLV-1 basic leucine zipper factor (HBZ) gene has a critical role in HTLV-1 infectivity and the development of ATL and HAM/TSP. However, little is known about the immune response against HBZ in HTLV-1-infected individuals. In this study, we examined antibody responses against HBZ in serum/plasma samples from 436 subjects including HTLV-1 seronegative donors, asymptomatic carriers (AC), ATL, and HAM/TSP patients using the luciferase immunoprecipitation system. RESULTS: Immunoreactivity against HBZ was detected in subsets of all HTLV-1-infected individuals but the test did not discriminate between AC, ATL and HAM/TSP. However, the frequency of detection of HBZ-specific antibodies in the serum of ATL patients with the chronic subtype was higher than in ATL patients with the lymphomatous subtype. Antibody responses against HBZ were also detected in cerebrospinal fluid of HAM/TSP patients with anti-HBZ in serum. Antibody responses against HBZ did not correlate with proviral load and HBZ mRNA expression in HAM/TSP patients, but the presence of an HBZ-specific response was associated with reduced CD4(+) T cell activation in HAM/TSP patients. Moreover, HBZ-specific antibody inhibited lymphoproliferation in the PBMC of HAM/TSP patients. CONCLUSIONS: This is the first report demonstrating humoral immune response against HBZ associated with HTLV-I infection. Thus, a humoral immune response against HBZ might play a role in HTLV-1 infection.",2013 Feb 13,"['Enose-Akahata, Yoshimi', 'Abrams, Anna', 'Massoud, Raya', 'Bialuk, Izabela', 'Johnson, Kory R', 'Green, Patrick L', 'Maloney, Elizabeth M', 'Jacobson, Steven']",Retrovirology,,,True
df4824b457c47934bafd828367bb0377132a903c,PMC,Modeling Host Genetic Regulation of Influenza Pathogenesis in the Collaborative Cross,http://dx.doi.org/10.1371/journal.ppat.1003196,PMC3585141,23468633,CC BY,"Genetic variation contributes to host responses and outcomes following infection by influenza A virus or other viral infections. Yet narrow windows of disease symptoms and confounding environmental factors have made it difficult to identify polymorphic genes that contribute to differential disease outcomes in human populations. Therefore, to control for these confounding environmental variables in a system that models the levels of genetic diversity found in outbred populations such as humans, we used incipient lines of the highly genetically diverse Collaborative Cross (CC) recombinant inbred (RI) panel (the pre-CC population) to study how genetic variation impacts influenza associated disease across a genetically diverse population. A wide range of variation in influenza disease related phenotypes including virus replication, virus-induced inflammation, and weight loss was observed. Many of the disease associated phenotypes were correlated, with viral replication and virus-induced inflammation being predictors of virus-induced weight loss. Despite these correlations, pre-CC mice with unique and novel disease phenotype combinations were observed. We also identified sets of transcripts (modules) that were correlated with aspects of disease. In order to identify how host genetic polymorphisms contribute to the observed variation in disease, we conducted quantitative trait loci (QTL) mapping. We identified several QTL contributing to specific aspects of the host response including virus-induced weight loss, titer, pulmonary edema, neutrophil recruitment to the airways, and transcriptional expression. Existing whole-genome sequence data was applied to identify high priority candidate genes within QTL regions. A key host response QTL was located at the site of the known anti-influenza Mx1 gene. We sequenced the coding regions of Mx1 in the eight CC founder strains, and identified a novel Mx1 allele that showed reduced ability to inhibit viral replication, while maintaining protection from weight loss.",2013 Feb 28,"['Ferris, Martin T.', 'Aylor, David L.', 'Bottomly, Daniel', 'Whitmore, Alan C.', 'Aicher, Lauri D.', 'Bell, Timothy A.', 'Bradel-Tretheway, Birgit', 'Bryan, Janine T.', 'Buus, Ryan J.', 'Gralinski, Lisa E.', 'Haagmans, Bart L.', 'McMillan, Leonard', 'Miller, Darla R.', 'Rosenzweig, Elizabeth', 'Valdar, William', 'Wang, Jeremy', 'Churchill, Gary A.', 'Threadgill, David W.', 'McWeeney, Shannon K.', 'Katze, Michael G.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.']",PLoS Pathog,,,True
be464c3787cad446a8be522f9ed4793c16c81b49,PMC,Direct Observation of Membrane Insertion by Enveloped Virus Matrix Proteins by Phosphate Displacement,http://dx.doi.org/10.1371/journal.pone.0057916,PMC3585246,23469104,CC BY,"Enveloped virus release is driven by poorly understood proteins that are functional analogs of the coat protein assemblies that mediate intracellular vesicle trafficking. We used differential electron density mapping to detect membrane integration by membrane-bending proteins from five virus families. This demonstrates that virus matrix proteins replace an unexpectedly large portion of the lipid content of the inner membrane face, a generalized feature likely to play a role in reshaping cellular membranes.",2013 Feb 28,"['Neuman, Benjamin W.', 'Kiss, Gabriella', 'Al-Mulla, Hawaa M. N.', 'Dokland, Terje', 'Buchmeier, Michael J.', 'Weikl, Thomas', 'Schley, David']",PLoS One,,,True
20656a048091de934d0fb432f8d070304a1664dd,PMC,Native Tertiary Structure and Nucleoside Modifications Suppress tRNA’s Intrinsic Ability to Activate the Innate Immune Sensor PKR,http://dx.doi.org/10.1371/journal.pone.0057905,PMC3587421,23483938,CC BY,"Interferon inducible protein kinase PKR is an essential component of innate immunity. It is activated by long stretches of dsRNA and provides the first line of host defense against pathogens by inhibiting translation initiation in the infected cell. Many cellular and viral transcripts contain nucleoside modifications and/or tertiary structure that could affect PKR activation. We have previously demonstrated that a 5′-end triphosphate–a signature of certain viral and bacterial transcripts–confers the ability of relatively unstructured model RNA transcripts to activate PKR to inhibit translation, and that this activation is abrogated by certain modifications present in cellular RNAs. In order to understand the biological implications of native RNA tertiary structure and nucleoside modifications on PKR activation, we study here the heavily modified cellular tRNAs and the unmodified or the lightly modified mitochondrial tRNAs (mt-tRNA). We find that both a T7 transcript of yeast tRNA(Phe) and natively extracted total bovine liver mt-tRNA activate PKR in vitro, whereas native E. coli, bovine liver, yeast, and wheat tRNA(Phe) do not, nor do a variety of base- or sugar-modified T7 transcripts. These results are further supported by activation of PKR by a natively folded T7 transcript of tRNA(Phe) in vivo supporting the importance of tRNA modification in suppressing PKR activation in cells. We also examine PKR activation by a T7 transcript of the A14G pathogenic mutant of mt-tRNA(Leu), which is known to dimerize, and find that the misfolded dimeric form activates PKR in vitro while the monomeric form does not. Overall, the in vitro and in vivo findings herein indicate that tRNAs have an intrinsic ability to activate PKR and that nucleoside modifications and native RNA tertiary folding may function, at least in part, to suppress such activation, thus serving to distinguish self and non-self tRNA in innate immunity.",2013 Mar 4,"['Nallagatla, Subba Rao', 'Jones, Christie N.', 'Ghosh, Saikat Kumar B.', 'Sharma, Suresh D.', 'Cameron, Craig E.', 'Spremulli, Linda L.', 'Bevilacqua, Philip C.']",PLoS One,,,True
e2bfc8942cb7075af5dea8abbb281e0a7ec146a8,PMC,Native Tertiary Structure and Nucleoside Modifications Suppress tRNA’s Intrinsic Ability to Activate the Innate Immune Sensor PKR,http://dx.doi.org/10.1371/journal.pone.0057905,PMC3587421,23483938,CC BY,"Interferon inducible protein kinase PKR is an essential component of innate immunity. It is activated by long stretches of dsRNA and provides the first line of host defense against pathogens by inhibiting translation initiation in the infected cell. Many cellular and viral transcripts contain nucleoside modifications and/or tertiary structure that could affect PKR activation. We have previously demonstrated that a 5′-end triphosphate–a signature of certain viral and bacterial transcripts–confers the ability of relatively unstructured model RNA transcripts to activate PKR to inhibit translation, and that this activation is abrogated by certain modifications present in cellular RNAs. In order to understand the biological implications of native RNA tertiary structure and nucleoside modifications on PKR activation, we study here the heavily modified cellular tRNAs and the unmodified or the lightly modified mitochondrial tRNAs (mt-tRNA). We find that both a T7 transcript of yeast tRNA(Phe) and natively extracted total bovine liver mt-tRNA activate PKR in vitro, whereas native E. coli, bovine liver, yeast, and wheat tRNA(Phe) do not, nor do a variety of base- or sugar-modified T7 transcripts. These results are further supported by activation of PKR by a natively folded T7 transcript of tRNA(Phe) in vivo supporting the importance of tRNA modification in suppressing PKR activation in cells. We also examine PKR activation by a T7 transcript of the A14G pathogenic mutant of mt-tRNA(Leu), which is known to dimerize, and find that the misfolded dimeric form activates PKR in vitro while the monomeric form does not. Overall, the in vitro and in vivo findings herein indicate that tRNAs have an intrinsic ability to activate PKR and that nucleoside modifications and native RNA tertiary folding may function, at least in part, to suppress such activation, thus serving to distinguish self and non-self tRNA in innate immunity.",2013 Mar 4,"['Nallagatla, Subba Rao', 'Jones, Christie N.', 'Ghosh, Saikat Kumar B.', 'Sharma, Suresh D.', 'Cameron, Craig E.', 'Spremulli, Linda L.', 'Bevilacqua, Philip C.']",PLoS One,,,False
15f3da54587d39ca8a3c8eabffb84fc463266ab0,PMC,Complete Genome Sequence of a Variant Porcine Epidemic Diarrhea Virus Strain Isolated in Central China,http://dx.doi.org/10.1128/genomeA.00243-12,PMC3587950,23469356,CC BY,"We report here the complete genome sequence of the porcine epidemic diarrhea virus strain CH/ZMDZY/11 isolated from central China. Our data, together with sequence data of porcine epidemic diarrhea virus (PEDV) isolates from other parts in China, will help to understand better the epidemiology and genetic diversity of PEDV field isolates in China.",2013 Feb 21,"['Wang, Xiao-Meng', 'Niu, Bei-Bei', 'Yan, He', 'Gao, Dong-Sheng', 'Huo, Jin-Yao', 'Chen, Lu', 'Chang, Hong-Tao', 'Wang, Chuan-qing', 'Zhao, Jun']",Genome Announc,,,True
757d0a46fdff943b64a2e8f7c6ac2132da44c6d5,PMC,"Ethyl 4-(5-bromo-1H-indol-3-yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexa­hydro­quinoline-3-carboxyl­ate",http://dx.doi.org/10.1107/S1600536812046909,PMC3588994,23476230,CC BY,"The title compound, C(23)H(25)BrN(2)O(3), crystallizes with two independent mol­ecules in the asymmetric unit (Z′ = 2) which differ in the twist of the 5-bromo-1H-indole ring with respect to the plane of the 4-methyl-1,4,5,6,7,8-hexa­hydro­quinoline ring [dihedral angles of 78.55 (9) and 89.70 (8)° in molecules A and B, respectively]. The indole ring is planar in both molecules [maximum deviations = 0.021 (3) and −0.020 (3) Å for the N atom] while the cyclo­hexene ring has adopts a sofa conformation. In the crystal, mol­ecules are linked by pairs of N—H⋯O hydrogen bonds, forming dimers with R (1) (2)(6) ring motifs. These dimers are connected by N—H⋯O hydrogen bonds, generating chains along [110]. A C—H⋯O contact occurs between the independent mol­ecules.",2012 Nov 24,"['Gündüz, Miyase Gözde', 'Butcher, Ray J.', 'Öztürk Yildirim, Sema', 'El-Khouly, Ahmed', 'Şafak, Cihat', 'Şimşek, Rahime']",Acta Crystallogr Sect E Struct Rep Online,,,True
b406fb73bb91dd7aed57b8187b69a5db7e83bd85,PMC,Using Routine Surveillance Data to Estimate the Epidemic Potential of Emerging Zoonoses: Application to the Emergence of US Swine Origin Influenza A H3N2v Virus,http://dx.doi.org/10.1371/journal.pmed.1001399,PMC3589342,23472057,CC BY,"BACKGROUND: Prior to emergence in human populations, zoonoses such as SARS cause occasional infections in human populations exposed to reservoir species. The risk of widespread epidemics in humans can be assessed by monitoring the reproduction number R (average number of persons infected by a human case). However, until now, estimating R required detailed outbreak investigations of human clusters, for which resources and expertise are not always available. Additionally, existing methods do not correct for important selection and under-ascertainment biases. Here, we present simple estimation methods that overcome many of these limitations. METHODS AND FINDINGS: Our approach is based on a parsimonious mathematical model of disease transmission and only requires data collected through routine surveillance and standard case investigations. We apply it to assess the transmissibility of swine-origin influenza A H3N2v-M virus in the US, Nipah virus in Malaysia and Bangladesh, and also present a non-zoonotic example (cholera in the Dominican Republic). Estimation is based on two simple summary statistics, the proportion infected by the natural reservoir among detected cases (G) and among the subset of the first detected cases in each cluster (F). If detection of a case does not affect detection of other cases from the same cluster, we find that R can be estimated by 1−G; otherwise R can be estimated by 1−F when the case detection rate is low. In more general cases, bounds on R can still be derived. CONCLUSIONS: We have developed a simple approach with limited data requirements that enables robust assessment of the risks posed by emerging zoonoses. We illustrate this by deriving transmissibility estimates for the H3N2v-M virus, an important step in evaluating the possible pandemic threat posed by this virus. Please see later in the article for the Editors' Summary",2013 Mar 5,"['Cauchemez, Simon', 'Epperson, Scott', 'Biggerstaff, Matthew', 'Swerdlow, David', 'Finelli, Lyn', 'Ferguson, Neil M.']",PLoS Med,,,True
2cf982b22e1f2deebca01ece2c70b0e4828ebc21,PMC,Clonal Expansions of CD8(+) T Cells with IL-10 Secreting Capacity Occur during Chronic Mycobacterium tuberculosis Infection,http://dx.doi.org/10.1371/journal.pone.0058612,PMC3589362,23472214,CC BY,"The exact role of CD8(+) T cells during Mycobacterium tuberculosis (Mtb) infection has been heavily debated, yet it is generally accepted that CD8(+) T cells contribute to protection against Mtb. In this study, however, we show that the Mtb-susceptible CBA/J mouse strain accumulates large numbers of CD8(+) T cells in the lung as infection progresses, and that these cells display a dysfunctional and immunosuppressive phenotype (PD-1(+), Tim-3(+), CD122(+)). CD8(+) T cell expansions from the lungs of Mtb-infected CBA/J mice were also capable of secreting the immunosuppressive cytokine interleukin-10 (IL-10), although in vivo CD8(+) T cell depletion did not significantly alter Mtb burden. Further analysis revealed that pulmonary CD8(+) T cells from Mtb-infected CBA/J mice were clonally expanded, preferentially expressing T cell receptor (TcR) Vβ chain 8 (8.2, 8.3) or Vβ 14. Although Vβ8(+) CD8(+) T cells were responsible for the majority of IL-10 production, in vivo depletion of Vβ8(+) did not significantly change the outcome of Mtb infection, which we hypothesize was a consequence of their dual IL-10/IFN-γ secreting profiles. Our data demonstrate that IL-10-secreting CD8(+) T cells can arise during chronic Mtb infection, although the significance of this T cell population in tuberculosis pathogenesis remains unclear.",2013 Mar 5,"['Cyktor, Joshua C.', 'Carruthers, Bridget', 'Beamer, Gillian L.', 'Turner, Joanne']",PLoS One,,,True
7b9bd316f8dddb71be863728f6dba041b0d6d402,PMC,Beet yellows virus replicase and replicative compartments: parallels with other RNA viruses,http://dx.doi.org/10.3389/fmicb.2013.00038,PMC3589766,23508802,CC BY,"In eukaryotic virus systems, infection leads to induction of membranous compartments in which replication occurs. Virus-encoded subunits of the replication complex mediate its interaction with membranes. As replication platforms, RNA viruses use the cytoplasmic surfaces of different membrane compartments, e.g., endoplasmic reticulum (ER), Golgi, endo/lysosomes, mitochondria, chloroplasts, and peroxisomes. Closterovirus infections are accompanied by formation of multivesicular complexes from cell membranes of ER or mitochondrial origin. So far the mechanisms for vesicles formation have been obscure. In the replication-associated 1a polyprotein of Beet yellows virus (BYV) and other closteroviruses, the region between the methyltransferase and helicase domains (1a central region (CR), 1a CR) is marginally conserved. Computer-assisted analysis predicts several putative membrane-binding domains in the BYV 1a CR. Transient expression of a hydrophobic segment (referred to here as CR-2) of the BYV 1a in Nicotiana benthamiana led to reorganization of the ER and formation of ~1-μm mobile globules. We propose that the CR-2 may be involved in the formation of multivesicular complexes in BYV-infected cells. This provides analogy with membrane-associated proteins mediating the build-up of “virus factories” in cells infected with diverse positive-strand RNA viruses (alpha-like viruses, picorna-like viruses, flaviviruses, and nidoviruses) and negative-strand RNA viruses (bunyaviruses).",2013 Mar 6,"['Gushchin, Vladimir A.', 'Solovyev, Andrey G.', 'Erokhina, Tatyana N.', 'Morozov, Sergey Y.', 'Agranovsky, Alexey A.']",Front Microbiol,,,True
7a31ec5e53aa0adf7ae3f8caa2b02b72d2123f37,PMC,Genomics and computational science for virus research,http://dx.doi.org/10.3389/fmicb.2013.00042,PMC3590459,23472060,CC BY,,2013 Mar 7,"['Sato, Hironori', 'Yokoyama, Masaru', 'Toh, Hiroyuki']",Front Microbiol,,,True
baa22aecb85ba7258afa2c07891ea8f08acdefa7,PMC,Exploratory Analysis of Methods for Automated Classification of Laboratory Test Orders into Syndromic Groups in Veterinary Medicine,http://dx.doi.org/10.1371/journal.pone.0057334,PMC3591392,23505427,CC BY,"BACKGROUND: Recent focus on earlier detection of pathogen introduction in human and animal populations has led to the development of surveillance systems based on automated monitoring of health data. Real- or near real-time monitoring of pre-diagnostic data requires automated classification of records into syndromes–syndromic surveillance–using algorithms that incorporate medical knowledge in a reliable and efficient way, while remaining comprehensible to end users. METHODS: This paper describes the application of two of machine learning (Naïve Bayes and Decision Trees) and rule-based methods to extract syndromic information from laboratory test requests submitted to a veterinary diagnostic laboratory. RESULTS: High performance (F(1)-macro = 0.9995) was achieved through the use of a rule-based syndrome classifier, based on rule induction followed by manual modification during the construction phase, which also resulted in clear interpretability of the resulting classification process. An unmodified rule induction algorithm achieved an F(1-micro) score of 0.979 though this fell to 0.677 when performance for individual classes was averaged in an unweighted manner (F(1-macro)), due to the fact that the algorithm failed to learn 3 of the 16 classes from the training set. Decision Trees showed equal interpretability to the rule-based approaches, but achieved an F(1-micro) score of 0.923 (falling to 0.311 when classes are given equal weight). A Naïve Bayes classifier learned all classes and achieved high performance (F(1-micro) = 0.994 and F(1-macro) = .955), however the classification process is not transparent to the domain experts. CONCLUSION: The use of a manually customised rule set allowed for the development of a system for classification of laboratory tests into syndromic groups with very high performance, and high interpretability by the domain experts. Further research is required to develop internal validation rules in order to establish automated methods to update model rules without user input.",2013 Mar 7,"['Dórea, Fernanda C.', 'Muckle, C. Anne', 'Kelton, David', 'McClure, JT.', 'McEwen, Beverly J.', 'McNab, W. Bruce', 'Sanchez, Javier', 'Revie, Crawford W.']",PLoS One,,,True
ecbee46a2f987fb95c2b1a5b0e4d789ea654a19e,PMC,Max Bergmann lecture Protein epitope mimetics in the age of structural vaccinology‡,http://dx.doi.org/10.1002/psc.2482,PMC3592999,23349031,CC BY,"This review highlights the growing importance of protein epitope mimetics in the discovery of new biologically active molecules and their potential applications in drug and vaccine research. The focus is on folded β-hairpin mimetics, which are designed to mimic β-hairpin motifs in biologically important peptides and proteins. An ever-growing number of protein crystal structures reveal how β-hairpin motifs often play key roles in protein–protein and protein–nucleic acid interactions. This review illustrates how using protein structures as a starting point for small-molecule mimetic design can provide novel ligands as protein–protein interaction inhibitors, as protease inhibitors, and as ligands for chemokine receptors and folded RNA targets, as well as novel antibiotics to combat the growing health threat posed by the emergence of antibiotic-resistant bacteria. The β-hairpin antibiotics are shown to target a β-barrel outer membrane protein (LptD) in Pseudomonas sp., which is essential for the biogenesis of the outer cell membrane. Another exciting prospect is that protein epitope mimetics will be of increasing importance in synthetic vaccine design, in the emerging field of structural vaccinology. Crystal structures of protective antibodies bound to their pathogen-derived epitopes provide an ideal starting point for the design of synthetic epitope mimetics. The mimetics can be delivered to the immune system in a highly immunogenic format on the surface of synthetic virus-like particles. The scientific challenges in molecular design remain great, but the potential significance of success in this area is even greater. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.",2013 Mar 24,"Robinson, John A",J Pept Sci,,,True
f60eb9280104d1ff7ca8ade5a7ccdeca43afce2f,PMC,Novel Human Gammapapillomavirus Species in a Nasal Swab,http://dx.doi.org/10.1128/genomeA.00022-13,PMC3593334,23516180,CC BY,"A divergent human gammapapillomavirus (γ-HPV) genome in a nasal swab from an elderly Finnish patient with respiratory symptoms was genetically characterized. The L1 gene of HPV-Fin864 shared <70% nucleotide identity to other reported γ-HPV genomes, provisionally qualifying it as a new species in the Gammapapillomavirus genus.",2013 Mar 7,"['Phan, Tung Gia', 'Vo, Nguyen P.', 'Aronen, Matti', 'Jartti, Laura', 'Jartti, Tuomas', 'Delwart, Eric']",Genome Announc,,,True
532e417a66dbe4822a3f8f9b496c105ccc7dd412,PMC,"Vaccination to Conserved Influenza Antigens in Mice Using a Novel Simian Adenovirus Vector, PanAd3, Derived from the Bonobo Pan paniscus",http://dx.doi.org/10.1371/journal.pone.0055435,PMC3594242,23536756,CC0,"Among approximately 1000 adenoviruses from chimpanzees and bonobos studied recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan paniscus) has one of the best profiles for a vaccine vector, combining potent transgene immunogenicity with minimal pre-existing immunity in the human population. In this study, we inserted into a replication defective PanAd3 a transgene expressing a fusion protein of conserved influenza antigens nucleoprotein (NP) and matrix 1 (M1). We then studied antibody and T cell responses as well as protection from challenge infection in a mouse model. A single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody and T cell responses, and protected against high dose lethal influenza virus challenge. Thus PanAd3 is a promising candidate vector for vaccines, including universal influenza vaccines.",2013 Mar 11,"['Vitelli, Alessandra', 'Quirion, Mary R.', 'Lo, Chia-Yun', 'Misplon, Julia A.', 'Grabowska, Agnieszka K.', 'Pierantoni, Angiolo', 'Ammendola, Virginia', 'Price, Graeme E.', 'Soboleski, Mark R.', 'Cortese, Riccardo', 'Colloca, Stefano', 'Nicosia, Alfredo', 'Epstein, Suzanne L.']",PLoS One,,,True
54ca96205e785170fff9f439860d4f4fa4d95782,PMC,The Role of Cysteine Proteinases and their Inhibitors in the Host-Pathogen Cross Talk,http://dx.doi.org/10.2174/138920312804871102,PMC3594739,23305363,CC BY,"Proteinases and their inhibitors play essential functional roles in basic biological processes in both hosts and pathogens. Endo/lysosomal cathepsins participate in immune response in pathogen recognition and elimination. They are essential for both antigen processing and presentation (host adaptive immune response) and activation of endosomal Toll like receptors (innate immune response). Pathogens can produce proteases and also natural inhibitors to subvert the host immune response. Several pathogens are sensed through the intracellular pathogen recognition receptors, but only some of them use the host proteolytic system to escape into the cytosol. In this review, I provide an update on the most recent developments regarding the role of proteinases and their inhibitors in the initiation and regulation of immune responses.",2012 Dec,"Kopitar-Jerala, Nataša",Curr Protein Pept Sci,,,True
8437870dfb10809764da7204fd758ff3e9ee85db,PMC,Dangerous liaisons: molecular basis for a syndemic relationship between Kaposi’s sarcoma and P. falciparum malaria,http://dx.doi.org/10.3389/fmicb.2013.00035,PMC3594938,23487416,CC BY,"The most severe manifestations of malaria (caused by Plasmodium falciparum) occur as a direct result of parasitemia following invasion of erythrocytes by post-liver blood-stage merozoites, and during subsequent cyto-adherence of infected erythrocytes to the vascular endothelium. However, the disproportionate epidemiologic clustering of severe malaria with aggressive forms of endemic diseases such as Kaposi’s sarcoma (KS), a neoplasm that is etiologically linked to infection with KS-associated herpesvirus (KSHV), underscores the significance of previously unexplored co-pathogenetic interactions that have the potential to modify the overall disease burden in co-infected individuals. Based on recent studies of the mechanisms that P. falciparum and KSHV have evolved to interact with their mutual human host, several new perspectives are emerging that highlight a surprising convergence of biological themes potentially underlying their associated co-morbidities. Against this background, ongoing studies are rapidly constructing a fascinating new paradigm in which the major host receptors that control parasite invasion (Basigin/CD147) and cyto-adherence (CD36) are, surprisingly, also important targets for exploitation by KSHV. In this article, we consider the major pathobiological implications of the co-option of Basigin/CD147 and CD36 signaling pathways by both P. falciparum and KSHV, not only as essential host factors for parasite persistence but also as important mediators of the pro-angiogenic phenotype within the virus-infected endothelial microenvironment. Consequently, the triangulation of interactions between P. falciparum, KSHV, and their mutual human host articulates a syndemic relationship that points to a conceptual framework for prevalence of aggressive forms of KS in malaria-endemic areas, with implications for the possibility of dual-use therapies against these debilitating infections in resource-limited parts of the world.",2013 Mar 12,"['Conant, Katelyn L.', 'Kaleeba, Johnan A. R.']",Front Microbiol,,,True
b75f738ed440a2a6bd3f129238c0e661024577cb,PMC,Harnessing DNA Synthesis to Develop Rapid Responses to Emerging and Pandemic Pathogens,http://dx.doi.org/10.4061/2011/765763,PMC3595711,23533775,CC BY,"Given the interconnected nature of our world today, emerging pathogens and pandemic outbreaks are an ever-growing threat to the health and economic stability of the global community. This is evident by the recent 2009 Influenza A (H1N1) pandemic, the SARS outbreak, as well as the ever-present threat of global bioterrorism. Fortunately, the biomedical community has been able to rapidly generate sequence data so these pathogens can be readily identified. To date, however, the utilization of this sequence data to rapidly produce relevant experimental results or actionable treatments is lagging in spite of obtained sequence data. Thus, a pathogenic threat that has emerged and/or developed into a pandemic can be rapidly identified; however, translating this identification into a targeted therapeutic or treatment that is rapidly available has not yet materialized. This commentary suggests that the growing technology of DNA synthesis should be fully implemented as a means to rapidly generate in vivo data and possibly actionable therapeutics soon after sequence data becomes available.",2011 Mar 16,"['Runco, Lisa M.', 'Coleman, J. Robert']",J Pathog,,,True
df783d511b145a10e7f609a87392eb50799d2b2b,PMC,"NOA36 Protein Contains a Highly Conserved Nucleolar Localization Signal Capable of Directing Functional Proteins to the Nucleolus, in Mammalian Cells",http://dx.doi.org/10.1371/journal.pone.0059065,PMC3596294,23516598,CC BY,"NOA36/ZNF330 is an evolutionarily well-preserved protein present in the nucleolus and mitochondria of mammalian cells. We have previously reported that the pro-apoptotic activity of this protein is mediated by a characteristic cysteine-rich domain. We now demonstrate that the nucleolar localization of NOA36 is due to a highly-conserved nucleolar localization signal (NoLS) present in residues 1–33. This NoLS is a sequence containing three clusters of two or three basic amino acids. We fused the amino terminal of NOA36 to eGFP in order to characterize this putative NoLS. We show that a cluster of three lysine residues at positions 3 to 5 within this sequence is critical for the nucleolar localization. We also demonstrate that the sequence as found in human is capable of directing eGFP to the nucleolus in several mammal, fish and insect cells. Moreover, this NoLS is capable of specifically directing the cytosolic yeast enzyme polyphosphatase to the target of the nucleolus of HeLa cells, wherein its enzymatic activity was detected. This NoLS could therefore serve as a very useful tool as a nucleolar marker and for directing particular proteins to the nucleolus in distant animal species.",2013 Mar 13,"['de Melo, Ivan S.', 'Jimenez-Nuñez, Maria D.', 'Iglesias, Concepción', 'Campos-Caro, Antonio', 'Moreno-Sanchez, David', 'Ruiz, Felix A.', 'Bolívar, Jorge']",PLoS One,,,True
8df99ad6d9b0d27c66f51580651c7bf1707bf275,PMC,"NOA36 Protein Contains a Highly Conserved Nucleolar Localization Signal Capable of Directing Functional Proteins to the Nucleolus, in Mammalian Cells",http://dx.doi.org/10.1371/journal.pone.0059065,PMC3596294,23516598,CC BY,"NOA36/ZNF330 is an evolutionarily well-preserved protein present in the nucleolus and mitochondria of mammalian cells. We have previously reported that the pro-apoptotic activity of this protein is mediated by a characteristic cysteine-rich domain. We now demonstrate that the nucleolar localization of NOA36 is due to a highly-conserved nucleolar localization signal (NoLS) present in residues 1–33. This NoLS is a sequence containing three clusters of two or three basic amino acids. We fused the amino terminal of NOA36 to eGFP in order to characterize this putative NoLS. We show that a cluster of three lysine residues at positions 3 to 5 within this sequence is critical for the nucleolar localization. We also demonstrate that the sequence as found in human is capable of directing eGFP to the nucleolus in several mammal, fish and insect cells. Moreover, this NoLS is capable of specifically directing the cytosolic yeast enzyme polyphosphatase to the target of the nucleolus of HeLa cells, wherein its enzymatic activity was detected. This NoLS could therefore serve as a very useful tool as a nucleolar marker and for directing particular proteins to the nucleolus in distant animal species.",2013 Mar 13,"['de Melo, Ivan S.', 'Jimenez-Nuñez, Maria D.', 'Iglesias, Concepción', 'Campos-Caro, Antonio', 'Moreno-Sanchez, David', 'Ruiz, Felix A.', 'Bolívar, Jorge']",PLoS One,,,False
f9faf42edda00faefb4ea08c2c4234b027990579,PMC,Human herpesvirus 6A induces apoptosis of HSB-2 cells via a mitochondrion-related caspase pathway(),http://dx.doi.org/10.1016/S1674-8301(10)60059-0,PMC3596692,23554661,CC BY,"Apoptosis plays an important role in the pathogenesis of viral infections. In this study, we investigated the cell death processes during productive HHV-6A infection and the underlying mechanisms. Annexin V-PI staining and electron microscopy indicated that HHV-6A is a strong inducer of apoptosis. HHV-6A infection decreased mitochondrial transmembrane potential and led to morphological changes of mitochondria. The cell death was associated with activation of caspase-3 and cleavage of DNA repair enzyme poly (ADP-ribose) polymerase, which is known to be an important substrate for activated caspase-3. Caspase-9 was activated significantly in HHV-6A-infected cells, whereas caspase-8 was not activated obviously. Moreover, HHV-6A infection upregulated Bax and downregulated Bcl-2. This is the first demonstration of mitochondrion-mediated, caspase-dependent apoptosis in HHV-6A-infected cells.",2010 Nov,"['Li, Lingyun', 'Chi, Jing', 'Zhou, Feng', 'Guo, Dandan', 'Wang, Fang', 'Liu, Genyan', 'Zhang, Chun', 'Yao, Kun']",J Biomed Res,,,True
e22140a30bea1676104edacd5240407c1f0d36a5,PMC,Comparative domain modeling of human EGF-like module EMR2 and study of interaction of the fourth domain of EGF with chondroitin 4-sulphate(),http://dx.doi.org/10.1016/S1674-8301(11)60013-4,PMC3596701,23554678,CC BY,"EMR2 is an EGF-like module containing mucin-like hormone receptor-2 precursor, a G-protein coupled receptor (G-PCR). Mutation in EMR2 causes complicated disorders like polycystic kidney disease (PKD). The structure of EMR2 shows that the fifth domain is comprised of EGF-TM7 helices. Functional assignment of EMR2 by support vector machine (SVM) revealed that along with transporter activity, several novel functions are predicted. A twenty amino acid sequence “MGGRVFLVFLAFCVWLTLPG” acts as the signal peptide responsible for posttranslational transport. Eight amino acids are involved in N-glycosylation sites and two cleavage sites are Leu517 and Ser518 in EMR2. The residue Arg241 is responsible for interaction with glycosaminoglycan and chondroitin sulfate. On the basis of structure, function and ligand binding sites, competitive EMR2 inhibitors designed may decrease the rate of human diseases like Usher's syndrome, bilateral frontoparietal polymicrogyria and PKD.",2011 Mar,"['Rani, Mukta', 'Dikhit, Manas R.', 'Sahoo, Ganesh C', 'Das, Pradeep']",J Biomed Res,,,True
2e6e30e494cf5e2216a4ac5cd2878a17ce8fc4b7,PMC,First introduction of pandemic influenza A/H1N1 and detection of respiratory viruses in pediatric patients in Central African Republic,http://dx.doi.org/10.1186/1743-422X-10-49,PMC3598402,23391188,CC BY,"BACKGROUND: Acute viral respiratory illnesses in children in sub-Saharan Africa have received relatively little attention, although they are much more frequent causes of morbidity and mortality than in developed countries. Active surveillance is essential to identify the causative agents and to improve clinical management, especially in the context of possible circulation of pandemic viruses. FINDINGS: A prospective study was conducted in the Central African Republic (CAR) between January and December 2010 among infants and children aged 0–15 years attending sentinel sites for influenza-like illness or acute respiratory illness. Nasopharyngeal swabs were collected, and one-step real-time and multiplex reverse transcription-polymerase chain reaction were used to detect respiratory viruses. Respiratory viruses were detected in 49 of the 329 (14.9%) nasopharyngeal samples: 29 (8.8%) contained influenza viruses (5 (1.5%) had pandemic influenza A/H1N1 virus and 24 (7.3%) had influenza B viruses), 11 (3.3%) contained parainfluenza viruses types 1 and 3 and 9 (2.7%) contained human respiratory syncytial virus. Most cases were detected during the rainy season in the CAR. Analysis of the amplicon sequences confirmed the identity of each detected virus. CONCLUSIONS: The influenza surveillance system in the CAR has provided valuable data on the seasonality of influenza and the circulation of other respiratory viruses. Our network could therefore play a valuable role in the prevention and control of influenza epidemics in the CAR.",2013 Feb 8,"['Nakouné, Emmanuel', 'Tricou, Vianney', 'Manirakiza, Alexandre', 'Komoyo, Francis', 'Selekon, Benjamin', 'Gody, Jean Chrysostome', 'Victoir, Kathleen', 'Buchy, Philippe', 'Kazanji, Mirdad']",Virol J,,,True
b6c747316db8f591a729c4ed060a6df0e3a18fc8,PMC,Inhaled corticosteroid use is associated with increased circulating T regulatory cells in children with asthma,http://dx.doi.org/10.1186/1476-7961-11-1,PMC3598778,23347774,CC BY,"BACKGROUND: T regulatory (Treg) cells are important in balancing immune responses and dysregulation of Treg cells has been implicated in the pathogenesis of multiple disease states including asthma. In this study, our primary aim was to determine Treg cell frequency in the peripheral blood of children with and without asthma. The secondary aim was to explore the association between Treg cell frequency with allergen sensitization, disease severity and medication use. METHODS: Peripheral blood mononuclear cells from healthy control subjects (N = 93) and asthmatic children of varying disease severity (N = 66) were characterized by multi-parameter flow cytometry. RESULTS: Our findings demonstrate that children with asthma had a significantly increased frequency of Treg cells compared to children without asthma. Using a multivariate model, increased Treg cell frequency in children with asthma was most directly associated with inhaled corticosteroid use, and not asthma severity, allergic sensitization, or atopic status of the asthma. CONCLUSION: We conclude that low dose, local airway administration of corticosteroids is sufficient to impact the frequency of Treg cells in the peripheral blood. These data highlight the importance of considering medication exposure when studying Treg cells and suggest inhaled corticosteroid use in asthmatics may improve disease control through increased Treg cell frequency.",2013 Jan 25,"['Singh, Anne Marie', 'Dahlberg, Paul', 'Burmeister, Kristjan', 'Evans, Michael D', 'Gangnon, Ronald', 'Roberg, Kathy A', 'Tisler, Christopher', 'DaSilva, Douglas', 'Pappas, Tressa', 'Salazar, Lisa', 'Lemanske, Robert F', 'Gern, James E', 'Seroogy, Christine M']",Clin Mol Allergy,,,True
1b8bd44173742cd254617aabc5fdf20fb98f4072,PMC,Severe lower respiratory tract infection in infants and toddlers from a non-affluent population: viral etiology and co-detection as risk factors,http://dx.doi.org/10.1186/1471-2334-13-41,PMC3598993,23351117,CC BY,"BACKGROUND: Lower respiratory tract infection (LRTI) is a major cause of pediatric morbidity and mortality, especially among non-affluent communities. In this study we determine the impact of respiratory viruses and how viral co-detections/infections can affect clinical LRTI severity in children in a hospital setting. METHODS: Patients younger than 3 years of age admitted to a tertiary hospital in Brazil during the months of high prevalence of respiratory viruses had samples collected from nasopharyngeal aspiration. These samples were tested for 13 different respiratory viruses through real-time PCR (rt-PCR). Patients were followed during hospitalization, and clinical data and population characteristics were collected during that period and at discharge to evaluate severity markers, especially length of hospital stay and oxygen use. Univariate regression analyses identified potential risk factors and multivariate logistic regressions were used to determine the impact of specific viral detections as well as viral co-detections in relation to clinical outcomes. RESULTS: We analyzed 260 episodes of LRTI with a viral detection rate of 85% (n = 222). Co-detection was observed in 65% of all virus-positive episodes. The most prevalent virus was Respiratory Syncytial Virus (RSV) (54%), followed by Human Metapneumovirus (hMPV) (32%) and Human Rhinovirus (HRV) (21%). In the multivariate models, infants with co-detection of HRV + RSV stayed 4.5 extra days (p = 0.004), when compared to infants without the co-detection. The same trends were observed for the outcome of days of supplemental oxygen use. CONCLUSIONS: Although RSV remains as the main cause of LRTI in infants our study indicates an increase in the length of hospital stay and oxygen use in infants with HRV detected by RT-PCR compared to those without HRV. Moreover, one can speculate that when HRV is detected simultaneously with RSV there is an additive effect that may be reflected in more severe clinical outcome. Also, our study identified a significant number of children infected by recently identified viruses, such as hMPV and Human Bocavirus (HBov), and this is a novel finding for poor communities from developing countries.",2013 Jan 25,"['da Silva, Emerson Rodrigues', 'Pitrez, Márcio Condessa Paulo', 'Arruda, Eurico', 'Mattiello, Rita', 'Sarria, Edgar E', 'de Paula, Flávia Escremim', 'Proença-Modena, José Luis', 'Delcaro, Luana Sella', 'Cintra, Otávio', 'Jones, Marcus H', 'Ribeiro, José Dirceu', 'Stein, Renato T']",BMC Infect Dis,,,True
956d1b132a0bb6b7ebd9ca19e312ef0fd7ca7cb9,PMC,Reverse transcription loop-mediated isothermal amplification assay for rapid detection of Bovine Rotavirus,http://dx.doi.org/10.1186/1746-6148-8-133,PMC3599620,22894568,CC BY,"BACKGROUND: Bovine rotavirus (BRV) infection is common in young calves. This viral infection causes acute diarrhea leading to death. Rapid identification of infected calves is essential to control BRV successfully. Therefore development of simple, highly specific, and sensitive detection method for BRV is needed. RESULTS: A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed and optimized for rapid detection of BRV. Specific primer sets were designed to target the sequences of the VP6 gene of the neonatal calf diarrhea virus (NCDV) strain of BRV. The RT-LAMP assay was performed in a water bath for 60 minutes at 63°C, and the amplification products were visualized either directly or under ultraviolet light. This BRV specific RT-LAMP assay could detect 3.32 copies of subtype A BRV. No cross-reactions were detected with other bovine pathogens. The ability of RT-LAMP to detect bovine rotavirus was further evaluated with 88 bovine rectal swab samples. Twenty-nine of these samples were found to be positive for BRV using RT-LAMP. The BRV-specific-RT-LAMP results were also confirmed by real-time RT-PCR assay. CONCLUSIONS: The bovine rotavirus-specific RT-LAMP assay was highly sensitive and holds promise as a prompt and simple diagnostic method for the detection of group A bovine rotavirus infection in young calves.",2012 Aug 15,"['Xie, Zhixun', 'Fan, Qing', 'Liu, Jiabo', 'Pang, Yaoshan', 'Deng, Xianwen', 'Xie, Zhiqin', 'Liji, Xie', 'Khan, Mazhar I']",BMC Vet Res,,,True
652fdea5cc6137511f2de628166875707670b10b,PMC,Ultra-deep mutant spectrum profiling: improving sequencing accuracy using overlapping read pairs,http://dx.doi.org/10.1186/1471-2164-14-96,PMC3599684,23402258,CC BY,"BACKGOUND: High throughput sequencing is beginning to make a transformative impact in the area of viral evolution. Deep sequencing has the potential to reveal the mutant spectrum within a viral sample at high resolution, thus enabling the close examination of viral mutational dynamics both within- and between-hosts. The challenge however, is to accurately model the errors in the sequencing data and differentiate real viral mutations, particularly those that exist at low frequencies, from sequencing errors. RESULTS: We demonstrate that overlapping read pairs (ORP) -- generated by combining short fragment sequencing libraries and longer sequencing reads -- significantly reduce sequencing error rates and improve rare variant detection accuracy. Using this sequencing protocol and an error model optimized for variant detection, we are able to capture a large number of genetic mutations present within a viral population at ultra-low frequency levels (<0.05%). CONCLUSIONS: Our rare variant detection strategies have important implications beyond viral evolution and can be applied to any basic and clinical research area that requires the identification of rare mutations.",2013 Feb 12,"['Chen-Harris, Haiyin', 'Borucki, Monica K', 'Torres, Clinton', 'Slezak, Tom R', 'Allen, Jonathan E']",BMC Genomics,,,True
57c211a07941fdfee4da06fd1e364234ea30b7f9,PMC,Ultra-deep mutant spectrum profiling: improving sequencing accuracy using overlapping read pairs,http://dx.doi.org/10.1186/1471-2164-14-96,PMC3599684,23402258,CC BY,"BACKGOUND: High throughput sequencing is beginning to make a transformative impact in the area of viral evolution. Deep sequencing has the potential to reveal the mutant spectrum within a viral sample at high resolution, thus enabling the close examination of viral mutational dynamics both within- and between-hosts. The challenge however, is to accurately model the errors in the sequencing data and differentiate real viral mutations, particularly those that exist at low frequencies, from sequencing errors. RESULTS: We demonstrate that overlapping read pairs (ORP) -- generated by combining short fragment sequencing libraries and longer sequencing reads -- significantly reduce sequencing error rates and improve rare variant detection accuracy. Using this sequencing protocol and an error model optimized for variant detection, we are able to capture a large number of genetic mutations present within a viral population at ultra-low frequency levels (<0.05%). CONCLUSIONS: Our rare variant detection strategies have important implications beyond viral evolution and can be applied to any basic and clinical research area that requires the identification of rare mutations.",2013 Feb 12,"['Chen-Harris, Haiyin', 'Borucki, Monica K', 'Torres, Clinton', 'Slezak, Tom R', 'Allen, Jonathan E']",BMC Genomics,,,False
402334dfcf4430553c3f99a5bbe869a3882c1d97,PMC,Porcine CD8α(dim/-)NKp46(high) NK cells are in a highly activated state,http://dx.doi.org/10.1186/1297-9716-44-13,PMC3599810,23452562,CC BY,"Natural Killer (NK) cells play a crucial role in the early phase of immune responses against various pathogens. In swine so far only little information about this lymphocyte population exists. Phenotypical analyses with newly developed monoclonal antibodies (mAbs) against porcine NKp46 recently revealed that in blood NKp46(-) and NKp46(+) cells with NK phenotype exist with comparable cytotoxic properties. In spleen a third NKp46-defined population with NK phenotype was observed that was characterised by a low to negative CD8α and increased NKp46 expression. In the current study it is shown that this NKp46(high) phenotype was correlated with an increased expression of CD16 and CD27 compared to the CD8α(+)NKp46(-) and NKp46(+) NK-cell subsets in spleen and blood. Additionally NKp46(high) NK cells expressed elevated levels of the chemokine receptor CXCR3 on mRNA level. Functional analyses revealed that splenic NKp46(high) NK cells produced much higher levels of Interferon-γ and Tumor Necrosis Factor-α upon stimulation with cytokines or phorbol-12-myristate-13-acetate/Ionomycin compared to the other two subsets. Furthermore, cross-linking of NKp46 by NKp46-specific mAbs led to a superior CD107a expression in the NKp46(high) NK cells, thus indicating a higher cytolytic capacity of this subset. Therefore porcine splenic NKp46(high) NK cells represent a highly activated subset of NK cells and may play a profound role in the immune surveillance of this organ.",2013 Mar 1,"['Mair, Kerstin H', 'Müllebner, Andrea', 'Essler, Sabine E', 'Duvigneau, J Catharina', 'Storset, Anne K', 'Saalmüller, Armin', 'Gerner, Wilhelm']",Vet Res,,,True
55648aad5bf29ad5e0eb50642764ff632d95843f,PMC,Porcine CD8α(dim/-)NKp46(high) NK cells are in a highly activated state,http://dx.doi.org/10.1186/1297-9716-44-13,PMC3599810,23452562,CC BY,"Natural Killer (NK) cells play a crucial role in the early phase of immune responses against various pathogens. In swine so far only little information about this lymphocyte population exists. Phenotypical analyses with newly developed monoclonal antibodies (mAbs) against porcine NKp46 recently revealed that in blood NKp46(-) and NKp46(+) cells with NK phenotype exist with comparable cytotoxic properties. In spleen a third NKp46-defined population with NK phenotype was observed that was characterised by a low to negative CD8α and increased NKp46 expression. In the current study it is shown that this NKp46(high) phenotype was correlated with an increased expression of CD16 and CD27 compared to the CD8α(+)NKp46(-) and NKp46(+) NK-cell subsets in spleen and blood. Additionally NKp46(high) NK cells expressed elevated levels of the chemokine receptor CXCR3 on mRNA level. Functional analyses revealed that splenic NKp46(high) NK cells produced much higher levels of Interferon-γ and Tumor Necrosis Factor-α upon stimulation with cytokines or phorbol-12-myristate-13-acetate/Ionomycin compared to the other two subsets. Furthermore, cross-linking of NKp46 by NKp46-specific mAbs led to a superior CD107a expression in the NKp46(high) NK cells, thus indicating a higher cytolytic capacity of this subset. Therefore porcine splenic NKp46(high) NK cells represent a highly activated subset of NK cells and may play a profound role in the immune surveillance of this organ.",2013 Mar 1,"['Mair, Kerstin H', 'Müllebner, Andrea', 'Essler, Sabine E', 'Duvigneau, J Catharina', 'Storset, Anne K', 'Saalmüller, Armin', 'Gerner, Wilhelm']",Vet Res,,,False
0656993afda296004221087271ce7e3dfe596c6c,PMC,Porcine CD8α(dim/-)NKp46(high) NK cells are in a highly activated state,http://dx.doi.org/10.1186/1297-9716-44-13,PMC3599810,23452562,CC BY,"Natural Killer (NK) cells play a crucial role in the early phase of immune responses against various pathogens. In swine so far only little information about this lymphocyte population exists. Phenotypical analyses with newly developed monoclonal antibodies (mAbs) against porcine NKp46 recently revealed that in blood NKp46(-) and NKp46(+) cells with NK phenotype exist with comparable cytotoxic properties. In spleen a third NKp46-defined population with NK phenotype was observed that was characterised by a low to negative CD8α and increased NKp46 expression. In the current study it is shown that this NKp46(high) phenotype was correlated with an increased expression of CD16 and CD27 compared to the CD8α(+)NKp46(-) and NKp46(+) NK-cell subsets in spleen and blood. Additionally NKp46(high) NK cells expressed elevated levels of the chemokine receptor CXCR3 on mRNA level. Functional analyses revealed that splenic NKp46(high) NK cells produced much higher levels of Interferon-γ and Tumor Necrosis Factor-α upon stimulation with cytokines or phorbol-12-myristate-13-acetate/Ionomycin compared to the other two subsets. Furthermore, cross-linking of NKp46 by NKp46-specific mAbs led to a superior CD107a expression in the NKp46(high) NK cells, thus indicating a higher cytolytic capacity of this subset. Therefore porcine splenic NKp46(high) NK cells represent a highly activated subset of NK cells and may play a profound role in the immune surveillance of this organ.",2013 Mar 1,"['Mair, Kerstin H', 'Müllebner, Andrea', 'Essler, Sabine E', 'Duvigneau, J Catharina', 'Storset, Anne K', 'Saalmüller, Armin', 'Gerner, Wilhelm']",Vet Res,,,False
eb5f4f63cdb4bfd57256d362dbd01063522c9f05,PMC,A mixed integer linear programming model to reconstruct phylogenies from single nucleotide polymorphism haplotypes under the maximum parsimony criterion,http://dx.doi.org/10.1186/1748-7188-8-3,PMC3599976,23343437,CC BY,"BACKGROUND: Phylogeny estimation from aligned haplotype sequences has attracted more and more attention in the recent years due to its importance in analysis of many fine-scale genetic data. Its application fields range from medical research, to drug discovery, to epidemiology, to population dynamics. The literature on molecular phylogenetics proposes a number of criteria for selecting a phylogeny from among plausible alternatives. Usually, such criteria can be expressed by means of objective functions, and the phylogenies that optimize them are referred to as optimal. One of the most important estimation criteria is the parsimony which states that the optimal phylogeny T(∗)for a set [Formula: see text] of n haplotype sequences over a common set of variable loci is the one that satisfies the following requirements: (i) it has the shortest length and (ii) it is such that, for each pair of distinct haplotypes [Formula: see text] , the sum of the edge weights belonging to the path from h(i) to h(j) in T(∗) is not smaller than the observed number of changes between h(i) and h(j). Finding the most parsimonious phylogeny for [Formula: see text] involves solving an optimization problem, called the Most Parsimonious Phylogeny Estimation Problem (MPPEP), which is [Formula: see text]-hard in many of its versions. RESULTS: In this article we investigate a recent version of the MPPEP that arises when input data consist of single nucleotide polymorphism haplotypes extracted from a population of individuals on a common genomic region. Specifically, we explore the prospects for improving on the implicit enumeration strategy of implicit enumeration strategy used in previous work using a novel problem formulation and a series of strengthening valid inequalities and preliminary symmetry breaking constraints to more precisely bound the solution space and accelerate implicit enumeration of possible optimal phylogenies. We present the basic formulation and then introduce a series of provable valid constraints to reduce the solution space. We then prove that these constraints can often lead to significant reductions in the gap between the optimal solution and its non-integral linear programming bound relative to the prior art as well as often substantially faster processing of moderately hard problem instances. CONCLUSION: We provide an indication of the conditions under which such an optimal enumeration approach is likely to be feasible, suggesting that these strategies are usable for relatively large numbers of taxa, although with stricter limits on numbers of variable sites. The work thus provides methodology suitable for provably optimal solution of some harder instances that resist all prior approaches.",2013 Jan 23,"['Catanzaro, Daniele', 'Ravi, Ramamoorthi', 'Schwartz, Russell']",Algorithms Mol Biol,,,True
74d9a4215dd1ab6d78bd9b6dbd2dc096c974cf4b,PMC,A novel coronavirus capable of lethal human infections: an emerging picture,http://dx.doi.org/10.1186/1743-422X-10-66,PMC3599982,23445530,CC BY,"SUMMARY: In September 2012, a novel coronavirus was isolated from a patient in Saudi Arabia who had died of an acute respiratory illness and renal failure. The clinical presentation was reminiscent of the outbreak caused by the SARS-coronavirus (SARS-CoV) exactly ten years ago that resulted in over 8000 cases. Sequence analysis of the new virus revealed that it was indeed a member of the same genus as SARS-CoV. By mid-February 2013, 12 laboratory-confirmed cases had been reported with 6 fatalities. The first 9 cases were in individuals resident in the Middle East, while the most recent 3 cases were in family members resident in the UK. The index case in the UK family cluster had travel history to Pakistan and Saudi Arabia. Although the current evidence suggests that this virus is not highly transmissible among humans, there is a real danger that it may spread to other parts of the world. Here, a brief review of the events is provided to summarize the rapidly emerging picture of this new virus.",2013 Feb 28,"Khan, Gulfaraz",Virol J,,,True
3fee471a12aa3fbfc3abab41a0f2604906c8acf0,PMC,Ecology of Zoonotic Infectious Diseases in Bats: Current Knowledge and Future Directions,http://dx.doi.org/10.1111/zph.12000,PMC3600532,22958281,CC BY,"Bats are hosts to a range of zoonotic and potentially zoonotic pathogens. Human activities that increase exposure to bats will likely increase the opportunity for infections to spill over in the future. Ecological drivers of pathogen spillover and emergence in novel hosts, including humans, involve a complex mixture of processes, and understanding these complexities may aid in predicting spillover. In particular, only once the pathogen and host ecologies are known can the impacts of anthropogenic changes be fully appreciated. Cross-disciplinary approaches are required to understand how host and pathogen ecology interact. Bats differ from other sylvatic disease reservoirs because of their unique and diverse lifestyles, including their ability to fly, often highly gregarious social structures, long lifespans and low fecundity rates. We highlight how these traits may affect infection dynamics and how both host and pathogen traits may interact to affect infection dynamics. We identify key questions relating to the ecology of infectious diseases in bats and propose that a combination of field and laboratory studies are needed to create data-driven mechanistic models to elucidate those aspects of bat ecology that are most critical to the dynamics of emerging bat viruses. If commonalities can be found, then predicting the dynamics of newly emerging diseases may be possible. This modelling approach will be particularly important in scenarios when population surveillance data are unavailable and when it is unclear which aspects of host ecology are driving infection dynamics.",2013 Feb,"['Hayman, D T S', 'Bowen, R A', 'Cryan, P M', 'McCracken, G F', 'O’Shea, T J', 'Peel, A J', 'Gilbert, A', 'Webb, C T', 'Wood, J L N']",Zoonoses Public Health,,,True
ab5652086c345dbe360ca35b48b31e43f95507e4,PMC,Reactomes of Porcine Alveolar Macrophages Infected with Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1371/journal.pone.0059229,PMC3602036,23527143,CC0,"Porcine reproductive and respiratory syndrome (PRRS) has devastated pig industries worldwide for many years. It is caused by a small RNA virus (PRRSV), which targets almost exclusively pig monocytes or macrophages. In the present study, five SAGE (serial analysis of gene expression) libraries derived from 0 hour mock-infected and 6, 12, 16 and 24 hours PRRSV-infected porcine alveolar macrophages (PAMs) produced a total 643,255 sequenced tags with 91,807 unique tags. Differentially expressed (DE) tags were then detected using the Bayesian framework followed by gene/mRNA assignment, arbitrary selection and manual annotation, which determined 699 DE genes for reactome analysis. The DAVID, KEGG and REACTOME databases assigned 573 of the DE genes into six biological systems, 60 functional categories and 504 pathways. The six systems are: cellular processes, genetic information processing, environmental information processing, metabolism, organismal systems and human diseases as defined by KEGG with modification. Self-organizing map (SOM) analysis further grouped these 699 DE genes into ten clusters, reflecting their expression trends along these five time points. Based on the number one functional category in each system, cell growth and death, transcription processes, signal transductions, energy metabolism, immune system and infectious diseases formed the major reactomes of PAMs responding to PRRSV infection. Our investigation also focused on dominant pathways that had at least 20 DE genes identified, multi-pathway genes that were involved in 10 or more pathways and exclusively-expressed genes that were included in one system. Overall, our present study reported a large set of DE genes, compiled a comprehensive coverage of pathways, and revealed system-based reactomes of PAMs infected with PRRSV. We believe that our reactome data provides new insight into molecular mechanisms involved in host genetic complexity of antiviral activities against PRRSV and lays a strong foundation for vaccine development to control PRRS incidence in pigs.",2013 Mar 19,"['Jiang, Zhihua', 'Zhou, Xiang', 'Michal, Jennifer J.', 'Wu, Xiao-Lin', 'Zhang, Lifan', 'Zhang, Ming', 'Ding, Bo', 'Liu, Bang', 'Manoranjan, Valipuram S.', 'Neill, John D.', 'Harhay, Gregory P.', 'Kehrli, Marcus E.', 'Miller, Laura C.']",PLoS One,,,True
11855c4ce9640d35da8dd4c54e913843a41c9252,PMC,"Prospective surveillance study of acute respiratory infections, influenza-like illness and seasonal influenza vaccine in a cohort of juvenile idiopathic arthritis patients",http://dx.doi.org/10.1186/1546-0096-11-10,PMC3602114,23510667,CC BY,"BACKGROUND: Acute respiratory infections (ARI) are frequent in children and complications can occur in patients with chronic diseases. We evaluated the frequency and impact of ARI and influenza-like illness (ILI) episodes on disease activity, and the immunogenicity and safety of influenza vaccine in a cohort of juvenile idiopathic arthritis (JIA) patients. METHODS: Surveillance of respiratory viruses was conducted in JIA patients during ARI season (March to August) in two consecutive years: 2007 (61 patients) and 2008 (63 patients). Patients with ARI or ILI had respiratory samples collected for virus detection by real time PCR. In 2008, 44 patients were immunized with influenza vaccine. JIA activity index (ACRPed30) was assessed during both surveillance periods. Influenza hemagglutination inhibition antibody titers were measured before and 30-40 days after vaccination. RESULTS: During the study period 105 ARI episodes were reported and 26.6% of them were ILI. Of 33 samples collected, 60% were positive for at least one virus. Influenza and rhinovirus were the most frequently detected, in 30% of the samples. Of the 50 JIA flares observed, 20% were temporally associated to ARI. Influenza seroprotection rates were higher than 70% (91-100%) for all strains, and seroconversion rates exceeded 40% (74-93%). In general, response to influenza vaccine was not influenced by therapy or disease activity, but patients using anti-TNF alpha drugs presented lower seroconversion to H1N1 strain. No significant differences were found in ACRPed30 after vaccination and no patient reported ILI for 6 months after vaccination. CONCLUSION: ARI episodes are relatively frequent in JIA patients and may have a role triggering JIA flares. Trivalent split influenza vaccine seems to be immunogenic and safe in JIA patients.",2013 Mar 7,"['Carvalho, Luciana M', 'de Paula, Flávia E', 'Silvestre, Rodrigo V D', 'Roberti, Luciana R', 'Arruda, Eurico', 'Mello, Wyller A', 'Ferriani, Virginia P L']",Pediatr Rheumatol Online J,,,True
d5076ff3eb3e96c862345fa109990f9a7b99b842,PMC,Evaluation on the Efficacy and Immunogenicity of Recombinant DNA Plasmids Expressing Spike Genes from Porcine Transmissible Gastroenteritis Virus and Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.1371/journal.pone.0057468,PMC3602451,23526943,CC BY,"Porcine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PDEV) can cause severe diarrhea in pigs. Development of effective vaccines against TGEV and PEDV is one of important prevention measures. The spike (S) protein is the surface glycoprotein of TGEV and PEDV, which can induce specific neutralization antibodies and is a candidate antigen for vaccination attempts. In this study, the open reading frames of the TGEV S1 protein and in addition of the S or S1 proteins of PEDV were inserted into the eukaryotic expression vector, pIRES, resulting in recombinant plasmids, pIRES-(TGEV-S1-PEDV-S1) and pIRES-(TGEV-S1-PEDV-S). Subsequently, 6–8 weeks old Kunming mice were inoculated with both DNA plasmids. Lymphocyte proliferation assay, virus neutralization assay, IFN-γ assay and CTL activity assay were performed. TGEV/PEDV specific antibody responses as well as kinetic changes of T lymphocyte subgroups of the immunized mice were analyzed. The results showed that the recombinant DNA plasmids increased the proliferation of T lymphocytes and the number of CD4+ and CD8+ T lymphocyte subgroups. In addition, the DNA vaccines induced a high level of IFN-γ in the immunized mice. The specific CTL activity in the pIRES-(TGEV-S1-PEDV-S) group became significant at 42 days post-immunization. At 35 days post-immunization, the recombinant DNA plasmids bearing full-length S genes of TGEV and PEDV stimulated higher levels of specific antibodies and neutralizing antibodies in immunized mice.",2013 Mar 19,"['Meng, Fandan', 'Ren, Yudong', 'Suo, Siqingaowa', 'Sun, Xuejiao', 'Li, Xunliang', 'Li, Pengchong', 'Yang, Wei', 'Li, Guangxing', 'Li, Lu', 'Schwegmann-Wessels, Christel', 'Herrler, Georg', 'Ren, Xiaofeng']",PLoS One,,,True
8620ebc72710ffd02328954e8447585ffcb5cae2,PMC,Role of Antidiarrhoeal Drugs as Adjunctive Therapies for Acute Diarrhoea in Children,http://dx.doi.org/10.1155/2013/612403,PMC3603675,23533446,CC BY,"Acute diarrhoea is a leading cause of child mortality in developing countries. Principal pathogens include Escherichia coli, rotaviruses, and noroviruses. 90% of diarrhoeal deaths are attributable to inadequate sanitation. Acute diarrhoea is the second leading cause of overall childhood mortality and accounts for 18% of deaths among children under five. In 2004 an estimated 1.5 million children died from diarrhoea, with 80% of deaths occurring before the age of two. Treatment goals are to prevent dehydration and nutritional damage and to reduce duration and severity of diarrhoeal episodes. The recommended therapeutic regimen is to provide oral rehydration solutions (ORS) and to continue feeding. Although ORS effectively mitigates dehydration, it has no effect on the duration, severity, or frequency of diarrhoeal episodes. Adjuvant therapy with micronutrients, probiotics, or antidiarrhoeal agents may thus be useful. The WHO recommends the use of zinc tablets in association with ORS. The ESPGHAN/ESPID treatment guidelines consider the use of racecadotril, diosmectite, or probiotics as possible adjunctive therapy to ORS. Only racecadotril and diosmectite reduce stool output, but no treatment has yet been shown to reduce hospitalisation rate or mortality. Appropriate management with validated treatments may help reduce the health and economic burden of acute diarrhoea in children worldwide.",2013 Mar 3,"Faure, Christophe",Int J Pediatr,,,True
f65cdf4a48c1ad11e613449dad480736e9d26945,PMC,Snapshot of Viral Infections in Wild Carnivores Reveals Ubiquity of Parvovirus and Susceptibility of Egyptian Mongoose to Feline Panleukopenia Virus,http://dx.doi.org/10.1371/journal.pone.0059399,PMC3603882,23527182,CC BY,"The exposure of wild carnivores to viral pathogens, with emphasis on parvovirus (CPV/FPLV), was assessed based on the molecular screening of tissue samples from 128 hunted or accidentally road-killed animals collected in Portugal from 2008 to 2011, including Egyptian mongoose (Herpestes ichneumon, n = 99), red fox (Vulpes vulpes, n = 19), stone marten (Martes foina, n = 3), common genet (Genetta genetta, n = 3) and Eurasian badger (Meles meles, n = 4). A high prevalence of parvovirus DNA (63%) was detected among all surveyed species, particularly in mongooses (58%) and red foxes (79%), along with the presence of CPV/FPLV circulating antibodies that were identified in 90% of a subset of parvovirus-DNA positive samples. Most specimens were extensively autolysed, restricting macro and microscopic investigations for lesion evaluation. Whenever possible to examine, signs of active disease were not present, supporting the hypothesis that the parvovirus vp2 gene fragments detected by real-time PCR possibly correspond to viral DNA reminiscent from previous infections. The molecular characterization of viruses, based on the analysis of the complete or partial sequence of the vp2 gene, allowed typifying three viral strains of mongoose and four red fox’s as feline panleukopenia virus (FPLV) and one stone marten’s as newCPV-2b type. The genetic similarity found between the FPLV viruses from free-ranging and captive wild species originated in Portugal and publicly available comparable sequences, suggests a closer genetic relatedness among FPLV circulating in Portugal. Although the clinical and epidemiological significance of infection could not be established, this study evidences that exposure of sympatric wild carnivores to parvovirus is common and geographically widespread, potentially carrying a risk to susceptible populations at the wildlife-domestic interface and to threatened species, such as the wildcat (Felis silvestris) and the critically endangered Iberian lynx (Lynx pardinus).",2013 Mar 20,"['Duarte, Margarida D.', 'Henriques, Ana Margarida', 'Barros, Sílvia Carla', 'Fagulha, Teresa', 'Mendonça, Paula', 'Carvalho, Paulo', 'Monteiro, Madalena', 'Fevereiro, Miguel', 'Basto, Mafalda P.', 'Rosalino, Luís Miguel', 'Barros, Tânia', 'Bandeira, Victor', 'Fonseca, Carlos', 'Cunha, Mónica V.']",PLoS One,,,True
f8290fc7f4fb355f1da52f816acfb2113691acb3,PMC,Retroviral and Lentiviral Vectors for the Induction of Immunological Tolerance,http://dx.doi.org/10.6064/2012/694137,PMC3605697,23526794,CC BY,"Retroviral and lentiviral vectors have proven to be particularly efficient systems to deliver genes of interest into target cells, either in vivo or in cell cultures. They have been used for some time for gene therapy and the development of gene vaccines. Recently retroviral and lentiviral vectors have been used to generate tolerogenic dendritic cells, key professional antigen presenting cells that regulate immune responses. Thus, three main approaches have been undertaken to induce immunological tolerance; delivery of potent immunosuppressive cytokines and other molecules, modification of intracellular signalling pathways in dendritic cells, and de-targeting transgene expression from dendritic cells using microRNA technology. In this review we briefly describe retroviral and lentiviral vector biology, and their application to induce immunological tolerance.",2012 Jul 18,"['Dufait, Inès', 'Liechtenstein, Therese', 'Lanna, Alessio', 'Bricogne, Christopher', 'Laranga, Roberta', 'Padella, Antonella', 'Breckpot, Karine', 'Escors, David']",Scientifica (Cairo),,,True
5ea028a50ee04aafff0b50ed954a3337176eca1b,PMC,Infiltration of Proinflammatory M1 Macrophages into the Outer Retina Precedes Damage in a Mouse Model of Age-Related Macular Degeneration,http://dx.doi.org/10.1155/2013/503725,PMC3606733,23533946,CC BY,"Age-related macular degeneration (AMD) is a major cause of blindness in the developed world. Oxidative stress and inflammation are implicated in AMD, but precise mechanisms remain poorly defined. Carboxyethylpyrrole (CEP) is an AMD-associated lipid peroxidation product. We previously demonstrated that mice immunized with CEP-modified albumin developed AMD-like degenerative changes in the outer retina. Here, we examined the kinetics of lesion development in immunized mice and the presence of macrophages within the interphotoreceptor matrix (IPM), between the retinal pigment epithelium and photoreceptor outer segments. We observed a significant and time-dependent increase in the number of macrophages in immunized mice relative to young age-matched controls prior to overt pathology. These changes were more pronounced in BALB/c mice than in C57BL/6 mice. Importantly, IPM-infiltrating macrophages were polarized toward the M1 phenotype but only in immunized mice. Moreover, when Ccr2-deficient mice were immunized, macrophages were not present in the IPM and no retinal lesions were observed, suggesting a deleterious role for these cells in our model. This work provides mechanistic evidence linking immune responses against oxidative damage with the presence of proinflammatory macrophages at sites of future AMD and experimentally demonstrates that manipulating immunity may be a target for modulating the development of AMD.",2013 Mar 7,"['Cruz-Guilloty, Fernando', 'Saeed, Ali M.', 'Echegaray, Jose J.', 'Duffort, Stephanie', 'Ballmick, Asha', 'Tan, Yaohong', 'Betancourt, Michel', 'Viteri, Eduardo', 'Ramkhellawan, Ghansham C.', 'Ewald, Eric', 'Feuer, William', 'Huang, DeQiang', 'Wen, Rong', 'Hong, Li', 'Wang, Hua', 'Laird, James M.', 'Sene, Abdoulaye', 'Apte, Rajendra S.', 'Salomon, Robert G.', 'Hollyfield, Joe G.', 'Perez, Victor L.']",Int J Inflam,,,False
d08ac6ac9dd268022b8cbe5cba116dd2bd12f757,PMC,Infiltration of Proinflammatory M1 Macrophages into the Outer Retina Precedes Damage in a Mouse Model of Age-Related Macular Degeneration,http://dx.doi.org/10.1155/2013/503725,PMC3606733,23533946,CC BY,"Age-related macular degeneration (AMD) is a major cause of blindness in the developed world. Oxidative stress and inflammation are implicated in AMD, but precise mechanisms remain poorly defined. Carboxyethylpyrrole (CEP) is an AMD-associated lipid peroxidation product. We previously demonstrated that mice immunized with CEP-modified albumin developed AMD-like degenerative changes in the outer retina. Here, we examined the kinetics of lesion development in immunized mice and the presence of macrophages within the interphotoreceptor matrix (IPM), between the retinal pigment epithelium and photoreceptor outer segments. We observed a significant and time-dependent increase in the number of macrophages in immunized mice relative to young age-matched controls prior to overt pathology. These changes were more pronounced in BALB/c mice than in C57BL/6 mice. Importantly, IPM-infiltrating macrophages were polarized toward the M1 phenotype but only in immunized mice. Moreover, when Ccr2-deficient mice were immunized, macrophages were not present in the IPM and no retinal lesions were observed, suggesting a deleterious role for these cells in our model. This work provides mechanistic evidence linking immune responses against oxidative damage with the presence of proinflammatory macrophages at sites of future AMD and experimentally demonstrates that manipulating immunity may be a target for modulating the development of AMD.",2013 Mar 7,"['Cruz-Guilloty, Fernando', 'Saeed, Ali M.', 'Echegaray, Jose J.', 'Duffort, Stephanie', 'Ballmick, Asha', 'Tan, Yaohong', 'Betancourt, Michel', 'Viteri, Eduardo', 'Ramkhellawan, Ghansham C.', 'Ewald, Eric', 'Feuer, William', 'Huang, DeQiang', 'Wen, Rong', 'Hong, Li', 'Wang, Hua', 'Laird, James M.', 'Sene, Abdoulaye', 'Apte, Rajendra S.', 'Salomon, Robert G.', 'Hollyfield, Joe G.', 'Perez, Victor L.']",Int J Inflam,,,True
5315d146c36ec79e45765ebf95759cfcad3a9f84,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,True
55ae9f78b75de806bbf7a4cc9f9b5e1d555f3b49,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
0a28e83bc38bca29c3fb0b446a346485c56c37ab,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
53d0e3f0cfe8c7e1f3d52a1c5a21a9ef62bf8d8e,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
09bb90a9f2bf8c12df5525b81a95b700d6096071,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
45a0829c6f38d9f4ea6321b844225743e8c7401d,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
d7222bc85d41d9bc5487ed14c5a070121a5dfa4a,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
ddff9be96a1c643fdc8d5dca5c5eaf2f537d9df5,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
84bd712908ff75807c275e8947b8ae96797f7c67,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
f795c7726f9ec87a62ddb0f2b23c9500a15b92db,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
9ab49a277ef0a3a15aba628771a22b8c2af6ede0,PMC,Genetic recombination in plant-infecting messenger-sense RNA viruses: overview and research perspectives,http://dx.doi.org/10.3389/fpls.2013.00068,PMC3607795,23533000,CC BY,"RNA recombination is one of the driving forces of genetic variability in (+)-strand RNA viruses. Various types of RNA–RNA crossovers were described including crosses between the same or different viral RNAs or between viral and cellular RNAs. Likewise, a variety of molecular mechanisms are known to support RNA recombination, such as replicative events (based on internal or end-to-end replicase switchings) along with non-replicative joining among RNA fragments of viral and/or cellular origin. Such mechanisms as RNA decay or RNA interference are responsible for RNA fragmentation and trans-esterification reactions which are likely accountable for ligation of RNA fragments. Numerous host factors were found to affect the profiles of viral RNA recombinants and significant differences in recombination frequency were observed among various RNA viruses. Comparative analyses of viral sequences allowed for the development of evolutionary models in order to explain adaptive phenotypic changes and co-evolving sites. Many questions remain to be answered by forthcoming RNA recombination research. (1) How various factors modulate the ability of viral replicase to switch templates, (2) What is the intracellular location of RNA–RNA template switchings, (3) Mechanisms and factors responsible for non-replicative RNA recombination, (4) Mechanisms of integration of RNA viral sequences with cellular genomic DNA, and (5) What is the role of RNA splicing and ribozyme activity. From an evolutionary stand point, it is not known how RNA viruses parasitize new host species via recombination, nor is it obvious what the contribution of RNA recombination is among other RNA modification pathways. We do not understand why the frequency of RNA recombination varies so much among RNA viruses and the status of RNA recombination as a form of sex is not well documented.",2013 Mar 26,"Bujarski, Jozef J.",Front Plant Sci,,,True
ecd247bf710a751792bb6ca40d0b8bcacf2d56ee,PMC,"ciliaFA: a research tool for automated, high-throughput measurement of ciliary beat frequency using freely available software",http://dx.doi.org/10.1186/2046-2530-1-14,PMC3607980,23351276,CC BY,"BACKGROUND: Analysis of ciliary function for assessment of patients suspected of primary ciliary dyskinesia (PCD) and for research studies of respiratory and ependymal cilia requires assessment of both ciliary beat pattern and beat frequency. While direct measurement of beat frequency from high-speed video recordings is the most accurate and reproducible technique it is extremely time consuming. The aim of this study was to develop a freely available automated method of ciliary beat frequency analysis from digital video (AVI) files that runs on open-source software (ImageJ) coupled to Microsoft Excel, and to validate this by comparison to the direct measuring high-speed video recordings of respiratory and ependymal cilia. These models allowed comparison to cilia beating between 3 and 52 Hz. METHODS: Digital video files of motile ciliated ependymal (frequency range 34 to 52 Hz) and respiratory epithelial cells (frequency 3 to 18 Hz) were captured using a high-speed digital video recorder. To cover the range above between 18 and 37 Hz the frequency of ependymal cilia were slowed by the addition of the pneumococcal toxin pneumolysin. Measurements made directly by timing a given number of individual ciliary beat cycles were compared with those obtained using the automated ciliaFA system. RESULTS: The overall mean difference (± SD) between the ciliaFA and direct measurement high-speed digital imaging methods was −0.05 ± 1.25 Hz, the correlation coefficient was shown to be 0.991 and the Bland-Altman limits of agreement were from −1.99 to 1.49 Hz for respiratory and from −2.55 to 3.25 Hz for ependymal cilia. CONCLUSIONS: A plugin for ImageJ was developed that extracts pixel intensities and performs fast Fourier transformation (FFT) using Microsoft Excel. The ciliaFA software allowed automated, high throughput measurement of respiratory and ependymal ciliary beat frequency (range 3 to 52 Hz) and avoids operator error due to selection bias. We have included free access to the ciliaFA plugin and installation instructions in Additional file 1 accompanying this manuscript that other researchers may use.",2012 Aug 1,"['Smith, Claire M', 'Djakow, Jana', 'Free, Robert C', 'Djakow, Petr', 'Lonnen, Rana', 'Williams, Gwyneth', 'Pohunek, Petr', 'Hirst, Robert A', 'Easton, Andrew J', 'Andrew, Peter W', 'O’Callaghan, Christopher']",Cilia,,,True
5ff8a6df6aa6e3ec16db9ff91702f691c18541df,PMC,Interaction of Bordetella bronchiseptica and Its Lipopolysaccharide with In Vitro Culture of Respiratory Nasal Epithelium,http://dx.doi.org/10.1155/2013/347086,PMC3608130,23555071,CC BY,"The nasal septa of fetal rabbits at 26 days of gestation were harvested by cesarean section of the does while under anesthesia and then exposed to Bordetella bronchiseptica or its lipopolysaccharide (LPS) for periods of 2 and 4 hours. A total of 240 explants were used. The tissues were examined using the Hematoxylin & Eosin technique. Then, semithin sections (0.5 μm) were stained with toluidine blue and examined with indirect immunoperoxidase (IPI) and lectin histochemistry. The most frequent and statistically significant findings were as follows: (1) cell death and increased goblet cell activity when exposed to bacteria and (2) cell death, cytoplasmic vacuolation and infiltration of polymorphonuclear leukocytes when exposed to LPS. The lesions induced by the bacterium were more severe than with LPS alone, except for the cytoplasmic vacuolation in epithelial cells. IPI stained the ciliated border of the epithelium with the bacterium more intensely, while LPS lectin histochemistry preferentially labeled the cytoplasm of goblet cell. These data indicate that B. bronchiseptica and its LPS may have an affinity for specific glycoproteins that would act as adhesion receptors in both locations.",2013 Mar 11,"['Gallego, Carolina', 'Middleton, Andrew M.', 'Martínez, Nhora', 'Romero, Stefany', 'Iregui, Carlos']",Vet Med Int,,,True
00951716e01c8e0cc341770389fc38d1b5455210,PMC,"Knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among urban high-risk groups: findings of a cross-sectional study in Dhaka, Bangladesh",http://dx.doi.org/10.1186/1471-2458-13-242,PMC3608226,23509860,CC BY,"BACKGROUND: In endemic countries such as Bangladesh, consequences of cholera place an enormous financial and social burden on patients and their families. Cholera vaccines not only provide health benefits to susceptible populations but also have effects on the earning capabilities and financial stability of the family. Community-based research and evaluations are necessary to understand perceptions about and practices of the community relating to cholera and oral cholera vaccines. This may help identify the ways in which such vaccines may be successfully introduced, and other preventive measures can be implemented. The present study assessed the knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among an urban population residing in a high cholera-prone setting in Dhaka, Bangladesh. METHODS: This cross-sectional study was conducted in an area of high cholera prevalence in 15 randomly-selected clusters in Mirpur, Dhaka city. A study team collected data through a survey and in-depth interviews during December 2010–February 2011. RESULTS: Of 2,830 families included in the final analysis, 23% could recognize cholera as acute watery diarrhea and 16% had ever heard of oral cholera vaccine. About 54% of the respondents had poor knowledge about cholera-related issues while 97% had a positive attitude toward cholera and oral cholera vaccine. One-third showed poor practice relating to the prevention of cholera. The findings showed a significant (p < 0.05) association between the respondents’ knowledge and sex, education, occupation, monthly overall household expenditure, attitudes and practice. In the adjusted model, male sex, having a lower monthly overall household expenditure, and having a less positive attitude toward cholera were the significant predictors to having poor knowledge. CONCLUSIONS: The findings suggest the strengthening of health education activities to improve knowledge on cholera, its prevention and treatment and information on cholera vaccination among high-risk populations. The data also underscore the potential of mass cholera vaccination to prevent and control cholera.",2013 Mar 19,"['Wahed, Tasnuva', 'Kaukab, Sheikh Shah Tanvir', 'Saha, Nirod Chandra', 'Khan, Iqbal Ansary', 'Khanam, Farhana', 'Chowdhury, Fahima', 'Saha, Amit', 'Khan, Ashraful Islam', 'Siddik, Ashraf Uddin', 'Cravioto, Alejandro', 'Qadri, Firdausi', 'Uddin, Jasim']",BMC Public Health,,,True
da9d4dfbed4a51ec017add0fe198ec753807f73a,PMC,"Knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among urban high-risk groups: findings of a cross-sectional study in Dhaka, Bangladesh",http://dx.doi.org/10.1186/1471-2458-13-242,PMC3608226,23509860,CC BY,"BACKGROUND: In endemic countries such as Bangladesh, consequences of cholera place an enormous financial and social burden on patients and their families. Cholera vaccines not only provide health benefits to susceptible populations but also have effects on the earning capabilities and financial stability of the family. Community-based research and evaluations are necessary to understand perceptions about and practices of the community relating to cholera and oral cholera vaccines. This may help identify the ways in which such vaccines may be successfully introduced, and other preventive measures can be implemented. The present study assessed the knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among an urban population residing in a high cholera-prone setting in Dhaka, Bangladesh. METHODS: This cross-sectional study was conducted in an area of high cholera prevalence in 15 randomly-selected clusters in Mirpur, Dhaka city. A study team collected data through a survey and in-depth interviews during December 2010–February 2011. RESULTS: Of 2,830 families included in the final analysis, 23% could recognize cholera as acute watery diarrhea and 16% had ever heard of oral cholera vaccine. About 54% of the respondents had poor knowledge about cholera-related issues while 97% had a positive attitude toward cholera and oral cholera vaccine. One-third showed poor practice relating to the prevention of cholera. The findings showed a significant (p < 0.05) association between the respondents’ knowledge and sex, education, occupation, monthly overall household expenditure, attitudes and practice. In the adjusted model, male sex, having a lower monthly overall household expenditure, and having a less positive attitude toward cholera were the significant predictors to having poor knowledge. CONCLUSIONS: The findings suggest the strengthening of health education activities to improve knowledge on cholera, its prevention and treatment and information on cholera vaccination among high-risk populations. The data also underscore the potential of mass cholera vaccination to prevent and control cholera.",2013 Mar 19,"['Wahed, Tasnuva', 'Kaukab, Sheikh Shah Tanvir', 'Saha, Nirod Chandra', 'Khan, Iqbal Ansary', 'Khanam, Farhana', 'Chowdhury, Fahima', 'Saha, Amit', 'Khan, Ashraful Islam', 'Siddik, Ashraf Uddin', 'Cravioto, Alejandro', 'Qadri, Firdausi', 'Uddin, Jasim']",BMC Public Health,,,False
54fb720924d357327cedcc8da45b5e0ceb5a0006,PMC,"A Laboratory Evaluation of Medicinal Herbs Used in China for the Treatment of Hand, Foot, and Mouth Disease",http://dx.doi.org/10.1155/2013/504563,PMC3608275,23554831,CC BY,"Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the causative agents of hand, foot, and mouth disease (HFMD). During recent epidemics of HFMD in China, medicinal herbals and preparations containing herbal extracts have demonstrated therapeutic efficacy with relative safety profiles. There have been no microbiological studies to validate their usefulness for HFMD. We selected 12 commonly used herbs for HFMD from government recommended guidelines as well as published reports and tested for their antiviral activity and anti-inflammatory activity. A water extract of Houttuynia cordata Thunb. (HCT) inhibited EV71 infection significantly and was marginally active against CVA16 infection. The IC(50) (concentration to have 50% inhibitory effect) values of HCT against a Fuyang strain and a BrCr strain of EV71 were determined at 8.9 μg/mL and 20.6 μg/mL, respectively. Mentha haplocalyx Briq. (MHB) water extract was active against CVA16, with an IC(50) value of 70.3 μg/mL. The extract did not exhibit activity against EV71 infection. Although the majority of the extracts showed no activity against viral infection, several extracts demonstrated activity in blocking proinflammatory response by viral infection. This study therefore validates the effectiveness of Chinese herbs for HFMD since some formulations containing the correct combination of the herbs can block viral replication as well as proinflammatory response of HFMD.",2013 Mar 10,"['Chen, Xiaoqing', 'Wang, Chunyang', 'Xu, Lanfang', 'Chen, Xiaoshuang', 'Wang, Wei', 'Yang, Guang', 'Tan, Ren Xiang', 'Li, Erguang', 'Jin, Yu']",Evid Based Complement Alternat Med,,,True
b263c0ae8e08257b2d46468d7561dbb7d7d6b6e8,PMC,Detection of human coronaviruses in simultaneously collected stool samples and nasopharyngeal swabs from hospitalized children with acute gastroenteritis,http://dx.doi.org/10.1186/1743-422X-10-46,PMC3610273,23379823,CC BY,"BACKGROUND: Human coronaviruses (HCoVs) are a well-known cause of respiratory infections but their role in gastrointestinal infections is unclear. The objective of our study was to assess the significance of HCoVs in the etiology of acute gastroenteritis (AGE) in children <6 years of age. METHODS: Stool samples and nasopharyngeal (NP) swabs collected from 260 children hospitalized for AGE (160 also had respiratory symptoms) and 157 otherwise healthy control children admitted for elective surgery were tested for the presence of four HCoVs using real time RT-PCR. Registered at ClinicalTrials.gov (reg. NCT00987519). RESULTS: HCoVs were more frequent in patients with AGE than in controls (23/260, 8.8% versus 4/151, 2.6%; odds ratio, OR 3.3; 95% confidence interval, CI 1.3–10.0; P = 0.01). Three of four HCoV-positive members in the control group, asymptomatic when sampled, recalled gastrointestinal or respiratory symptoms within the previous 14 days. In patients with AGE, HCoVs were present in NP samples more often than in stools (22/256, 8.6%, versus 6/260, 2.3%; P = 0.0004). In 5/6 children with HCoVs detected in stools, the viruses were also detected in NP swabs. Patients had a significantly higher probability of HCoV detection in stool (OR 4; 95% CI 1.4–15.3; P = 0.006) and also in stool and/or NP (OR 3.3, 95% CI 1.3–10.0; P = 0.01) than healthy controls. All four HCoVs species were detected in stool and NP samples. CONCLUSIONS: Although HCoVs were more frequently detected in patients with AGE than in the control group, high prevalence of HCoVs in NP swabs compounded by their low occurrence in stool samples and detection of other viruses in stool samples, indicate that HCoVs probably play only a minor role in causing gastrointestinal illness in children <6 years old.",2013 Feb 5,"['Jevšnik, Monika', 'Steyer, Andrej', 'Zrim, Tamara', 'Pokorn, Marko', 'Mrvič, Tatjana', 'Grosek, Štefan', 'Strle, Franc', 'Lusa, Lara', 'Petrovec, Miroslav']",Virol J,,,True
190bc9d8aadbfb5c848ccdb9f4fa98610780ba56,PMC,Saikosaponin-d Enhances the Anticancer Potency of TNF-α via Overcoming Its Undesirable Response of Activating NF-Kappa B Signalling in Cancer Cells,http://dx.doi.org/10.1155/2013/745295,PMC3610377,23573150,CC BY,"Tumor necrosis factor-alpha (TNF-α) was reported as anticancer therapy due to its cytotoxic effect against an array of tumor cells. However, its undesirable responses of TNF-α on activating NF-κB signaling and pro-metastatic property limit its clinical application in treating cancers. Therefore, sensitizing agents capable of overcoming this undesirable effect must be valuable for facilitating the usage of TNF-α-mediated apoptosis therapy for cancer patients. Previously, saikosaponin-d (Ssd), a triterpene saponin derived from the medicinal plant, Bupleurum falcatum L. (Umbelliferae), showed to exhibit a variety of pharmacological activities such as antiinflammation, antibacteria, antivirus and anticancer. Recently, we found that Ssd could inhibit the activated T lymphocytes via suppression of NF-κB, NF-AT and AP-1 signaling. Here, we showed that Ssd significantly potentiated TNF-α-mediated cell death in HeLa and HepG2 cancer cells via suppression of TNF-α-induced NF-κB activation and its target genes expression involving cancer cell proliferation, invasion, angiogenesis and survival. Also, Ssd revealed a significant potency of abolishing TNF-α-induced cancer cell invasion and angiogenesis in HUVECs while inducing apoptosis via enhancing the loss of mitochondrial membrane potential in HeLa cells. Collectively, these findings indicate that Ssd has a significant potential to be developed as a combined adjuvant remedy with TNF-α for cancer patients.",2013 Mar 12,"['Wong, Vincent Kam Wai', 'Zhang, Molly Miao', 'Zhou, Hua', 'Lam, Kelly Yin Ching', 'Chan, Po Ling', 'Law, Carmen Ka Man', 'Yue, Patrick Ying Kit', 'Liu, Liang']",Evid Based Complement Alternat Med,,,True
10a769cac0a76b41a6a82be148c1a2675e9d4604,PMC,TIM-family Proteins Promote Infection of Multiple Enveloped Viruses through Virion-associated Phosphatidylserine,http://dx.doi.org/10.1371/journal.ppat.1003232,PMC3610696,23555248,CC BY,"Human T-cell Immunoglobulin and Mucin-domain containing proteins (TIM1, 3, and 4) specifically bind phosphatidylserine (PS). TIM1 has been proposed to serve as a cellular receptor for hepatitis A virus and Ebola virus and as an entry factor for dengue virus. Here we show that TIM1 promotes infection of retroviruses and virus-like particles (VLPs) pseudotyped with a range of viral entry proteins, in particular those from the filovirus, flavivirus, New World arenavirus and alphavirus families. TIM1 also robustly enhanced the infection of replication-competent viruses from the same families, including dengue, Tacaribe, Sindbis and Ross River viruses. All interactions between TIM1 and pseudoviruses or VLPs were PS-mediated, as demonstrated with liposome blocking and TIM1 mutagenesis experiments. In addition, other PS-binding proteins, such as Axl and TIM4, promoted infection similarly to TIM1. Finally, the blocking of PS receptors on macrophages inhibited the entry of Ebola VLPs, suggesting that PS receptors can contribute to infection in physiologically relevant cells. Notably, infection mediated by the entry proteins of Lassa fever virus, influenza A virus and SARS coronavirus was largely unaffected by TIM1 expression. Taken together our data show that TIM1 and related PS-binding proteins promote infection of diverse families of enveloped viruses, and may therefore be useful targets for broad-spectrum antiviral therapies.",2013 Mar 28,"['Jemielity, Stephanie', 'Wang, Jinyize J.', 'Chan, Ying Kai', 'Ahmed, Asim A.', 'Li, Wenhui', 'Monahan, Sheena', 'Bu, Xia', 'Farzan, Michael', 'Freeman, Gordon J.', 'Umetsu, Dale T.', 'DeKruyff, Rosemarie H.', 'Choe, Hyeryun']",PLoS Pathog,,,True
0ac675fdff45bfddf5aea34d37f58ad7df4f78b9,PMC,"Genome and Bioinformatic Analysis of a HAdV-B14p1 Virus Isolated from a Baby with Pneumonia in Beijing, China",http://dx.doi.org/10.1371/journal.pone.0060345,PMC3612040,23555956,CC BY,"The genome of HAdV-B14p1 strain BJ430, isolated from a six-month-old baby diagnosed with bronchial pneumonia at the Beijing Children’s Hospital in December 2010, was sequenced, analyzed, and compared with reference adenovirus genome sequences archived in GenBank. This genome is 34,762 bp in length, remarkably presenting 99.9% identity with the genome from HAdV14p1 strain 303600, which was isolated in the USA (2006). Even more remarkable, it is 99.7% identical with the HAdV-B14p (prototype “de Wit” strain) genome, isolated from The Netherlands in 1955. The patient and its parents presumably had no or limited contact with persons from the USA and Ireland, both of which reported outbreaks of the re-emergent virus HAdV-14p1 recently. These genome data, its analysis, and this report provide a reference for any additional HAdV-B14 outbreak in China and provide the basis for the development of adenovirus vaccines and molecular pathogen surveillance protocols in high-risk areas.",2013 Mar 29,"['Tang, Liuying', 'An, Junjing', 'Xie, Zhengde', 'Dehghan, Shoaleh', 'Seto, Donald', 'Xu, Wenbo', 'Ji, Yixin']",PLoS One,,,True
7722e2866e2b7849cc2f3175430a1048d97b71d9,PMC,Use of Transgenic Animals in Biotechnology: Prospects and Problems,,PMC3612824,23556129,CC BY,"During the past two decades, there have been numerous attempts at using animals in order to produce recombinant human proteins and monoclonal antibodies. However, it is only recently that the first two therapeutic agents isolated from the milk of transgenic animals, C1 inhibitor (Ruconest) and antithrombin (ATryn), appeared on the market. This inspires hope that a considerable number of new recombinant proteins created using such technology could become available for practical use in the near future. In this review, the methods applied to produce transgenic animals are described and the advantages and drawbacks related to their use for producing recombinant human proteins and monoclonal antibodies are discussed.",2013 Jan-Mar,"['Maksimenko, O. G.', 'Deykin, A.V.', 'Khodarovich, Yu. M.', 'Georgiev, P. G.']",Acta Naturae,,,True
d1a0400f1b97c8f05e14aa43796802ccec11f506,PMC,Airflow Dynamics of Human Jets: Sneezing and Breathing - Potential Sources of Infectious Aerosols,http://dx.doi.org/10.1371/journal.pone.0059970,PMC3613375,23560060,CC BY,"Natural human exhalation flows such as coughing, sneezing and breathing can be considered as ‘jet-like’ airflows in the sense that they are produced from a single source in a single exhalation effort, with a relatively symmetrical, conical geometry. Although coughing and sneezing have garnered much attention as potential, explosive sources of infectious aerosols, these are relatively rare events during daily life, whereas breathing is necessary for life and is performed continuously. Real-time shadowgraph imaging was used to visualise and capture high-speed images of healthy volunteers sneezing and breathing (through the nose – nasally, and through the mouth - orally). Six volunteers, who were able to respond to the pepper sneeze stimulus, were recruited for the sneezing experiments (2 women: 27.5±6.36 years; 4 men: 29.25±10.53 years). The maximum visible distance over which the sneeze plumes (or puffs) travelled was 0.6 m, the maximum sneeze velocity derived from these measured distances was 4.5 m/s. The maximum 2-dimensional (2-D) area of dissemination of these sneezes was 0.2 m(2). The corresponding derived parameter, the maximum 2-D area expansion rate of these sneezes was 2 m(2)/s. For nasal breathing, the maximum propagation distance and derived velocity were 0.6 m and 1.4 m/s, respectively. The maximum 2-D area of dissemination and derived expansion rate were 0.11 m(2) and 0.16 m(2)/s, respectively. Similarly, for mouth breathing, the maximum propagation distance and derived velocity were 0.8 m and 1.3 m/s, respectively. The maximum 2-D area of dissemination and derived expansion rate were 0.18 m(2) and 0.17 m(2)/s, respectively. Surprisingly, a comparison of the maximum exit velocities of sneezing reported here with those obtained from coughing (published previously) demonstrated that they are relatively similar, and not extremely high. This is in contrast with some earlier estimates of sneeze velocities, and some reasons for this difference are discussed.",2013 Apr 1,"['Tang, Julian W.', 'Nicolle, Andre D.', 'Klettner, Christian A.', 'Pantelic, Jovan', 'Wang, Liangde', 'Suhaimi, Amin Bin', 'Tan, Ashlynn Y. L.', 'Ong, Garrett W. X.', 'Su, Ruikun', 'Sekhar, Chandra', 'Cheong, David D. W.', 'Tham, Kwok Wai']",PLoS One,,,True
4cb55c99b99ef1944a0b43b342a8bc9eda6ae227,PMC,Strategies to develop antivirals against enterovirus 71,http://dx.doi.org/10.1186/1743-422X-10-28,PMC3614426,23339605,CC BY,"Enterovirus 71 (EV71) is an important human pathogen which may cause severe neurological complications and death in children. The virus caused several outbreaks in the Asia-Pacific region during the past two decades and has been considered a significant public health problem in the post-poliovirus eradication era. Unlike poliovirus, there is no effective vaccine or approved antivirals against EV71. To explore anti-EV71 agents therefore is of vital importance. Several strategies have been employed to develop antivirals based on the molecular characteristics of the virus. Among these, some small molecules that were developed against human rhinoviruses and poliovirus are under evaluation. In this review, we discuss the recent development of such small molecules against EV71, known drug resistance and possible solutions to it, and animal models for evaluating the efficacy of these antivirals. Although further investigation is required for clinical applications of the existing candidates, the molecular mechanisms revealed for the inhibition of EV71 replication can be used for designing new molecules against this virus in the future.",2013 Jan 22,"['Kuo, Rei-Lin', 'Shih, Shin-Ru']",Virol J,,,True
896cfa254a80c192a7aa872d955e750d6280e071,PMC,Seroepidemiological Study on SARS-CoV IgG Antibodies of Different Populations from Several Areas,,PMC3614584,23674957,CC BY,"OBJECTIVE: In order to investigate the clinical and epidemiological rules of severe acute respiratory syndrome (SARS), rates and levels SARS coronavirus (SARS-CoV) IgG antibodies of the patients and community populations from several areas were detected. METHODS: Indirect immunofluorescent assay (IFA) and double-antigen sandwich enzyme-linked immunosorbent assay (ELISA) were used to detect the SARS coronavirus-specific IgG antibodies in sera of 1700, including 1453 general populations from Hongkong, Marco, Guangzhou and Peking and 257 SARS patients from Guangzhou and Peking. The dynamics of the serum antibodies of SARS patients were observed from 3 to 360 days after onset of symptoms. RESULTS: 90% of 257 patient serum specimens after 20 days of disease onset showed positive SARS-CoV IgG either using ELISA or IFA. 257 SARS patients, antibodies titers increased steadily in early 4 to 6 months after onset of SARS. The titers of most cases came to the peak in the 6th month. then antibodies titers declined rapidly in some cases. However, all specimens still were positive for SARS-CoV IgG in the 48th month. CONCLUSIONS: This study suggest that few inapparent infectious patients exist during SARS epidemic. Serum IgG antibodies has diagnostic value for SARS in the late course of disease and the antibodies present more than 48 months.",2005 Jun,"['Shi, Yu-ling', 'Li, Lin-hai', 'Chu, Xin-wei', 'Chen, Qing', 'Wang, Yun-long', 'Ma, Qing-jun', 'Cao, Cheng', 'Yu, Shou-yi']",Int J Biomed Sci,,,True
f0766282327201e2f62b12f14326960106083d73,PMC,Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors,http://dx.doi.org/10.1371/journal.pone.0060838,PMC3614905,23573288,CC BY,"Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes.",2013 Apr 2,"['Brudner, Matthew', 'Karpel, Marshall', 'Lear, Calli', 'Chen, Li', 'Yantosca, L. Michael', 'Scully, Corinne', 'Sarraju, Ashish', 'Sokolovska, Anna', 'Zariffard, M. Reza', 'Eisen, Damon P.', 'Mungall, Bruce A.', 'Kotton, Darrell N.', 'Omari, Amel', 'Huang, I-Chueh', 'Farzan, Michael', 'Takahashi, Kazue', 'Stuart, Lynda', 'Stahl, Gregory L.', 'Ezekowitz, Alan B.', 'Spear, Gregory T.', 'Olinger, Gene G.', 'Schmidt, Emmett V.', 'Michelow, Ian C.']",PLoS One,,,True
15640dc97f36ae7b410f731003235ee8a3cae495,PMC,Downregulation of Signaling-active IGF-1 by Dipeptidyl Peptidase IV (DPP-IV),,PMC3615292,23675206,CC BY,"Functioning as an extracellular protease, dipeptidyl peptidase IV (DPP-IV) preferentially cleaves the peptide bond after the penultimate proline residue. We report here that DPP-IV cleaves the first two amino acids from insulin-like growth factor 1 (IGF-1), revealed by mass spectrometry. The kinetic parameters of the proteolytic cleavage indicate that this reaction is physiologically relevant. Interestingly, truncated IGF-1 is less potent than the full-length protein in activating the IGF-1R, but binds more readily to IGF-binding protein 3 (IGFBP3). Quantitative RT–PCR showed that the level of DPP-IV mRNA is dramatically lower in lung squamous cell carcinoma tissues than in adjacent nonneoplastic lung tissues. However, this reduction was not observed in lung adenocarcinoma tissues. Our study suggests a possible link between IGF-1 and DPP-IV in cancer development in a specific tumor niche. A DPP-IV-related pathway may be important in mitigating IGF-1 signaling. Consequently, a robust IGF signaling pathway may accelerate early carcinogenesis in environments lacking DPP-IV.",2010 Dec,"['Lin, Ching-Ting', 'Tang, Hsiang-Yun', 'Han, Yu-San', 'Liu, Hui-Ping', 'Huang, Shiu-Feng', 'Chien, Chia-Hui', 'Shyy, John', 'Chiu, Jeng-Jian', 'Chen, Xin']",Int J Biomed Sci,,,True
424061f2444cab0c4e972c7fcfc18a9dfbe7b4c6,PMC,Is the reporting timeliness gap for avian flu and H1N1 outbreaks in global health surveillance systems associated with country transparency?,http://dx.doi.org/10.1186/1744-8603-9-14,PMC3615947,23531369,CC BY,"BACKGROUND: This study aims to evaluate the length of time elapsed between reports of the same incidents related to avian flu and H1N1 outbreaks published by the WHO and ProMED-mail, the two major global health surveillance systems, before and after the amendment of the International Health Regulations in 2005 (IHR 2005) and to explore the association between country transparency and this timeliness gap. METHODS: We recorded the initial release dates of each report related to avian flu or H1N1 listed on the WHO Disease Outbreak News site and the matching outbreak report from ProMED-mail, a non-governmental program for monitoring emerging diseases, from 2003 to the end of June 2009. The timeliness gap was calculated as the difference in days between the report release dates of the matching outbreaks in the WHO and ProMED-mail systems. Civil liberties scores were collected as indicators of the transparency of each country. The Human Development Index and data indicating the density of physicians and nurses were collected to reflect countries’ development and health workforce statuses. Then, logistic regression was performed to determine the correlation between the timeliness gap and civil liberties, human development, and health workforce status, controlling for year. RESULTS: The reporting timeliness gap for avian flu and H1N1 outbreaks significantly decreased after 2003. On average, reports were posted 4.09 (SD = 7.99) days earlier by ProMED-mail than by the WHO. Countries with partly free (OR = 5.77) and free civil liberties scores (OR = 10.57) had significantly higher likelihoods of longer timeliness gaps than non-free countries. Similarly, countries with very high human development status had significantly higher likelihoods of longer timeliness gaps than countries with middle or low human development status (OR = 5.30). However, no association between the timeliness gap and health workforce density was found. CONCLUSION: The study found that the adoption of IHR 2005, which contributed to countries’ awareness of the importance of timely reporting, had a significant impact in improving the reporting timeliness gap. In addition, the greater the civil liberties in a country (e.g., importance of freedom of the media), the longer the timeliness gap.",2013 Mar 25,"['Tsai, Feng-Jen', 'Tseng, Eva', 'Chan, Chang-Chuan', 'Tamashiro, Hiko', 'Motamed, Sandrine', 'Rougemont, André C']",Global Health,,,True
e0e5e7bee4a69a83d9cffeefcdcc26172d56f1a4,PMC,Rab11-FIP1C and Rab14 Direct Plasma Membrane Sorting and Particle Incorporation of the HIV-1 Envelope Glycoprotein Complex,http://dx.doi.org/10.1371/journal.ppat.1003278,PMC3616983,23592992,CC BY,"The incorporation of the envelope glycoprotein complex (Env) onto the developing particle is a crucial step in the HIV-1 lifecycle. The long cytoplasmic tail (CT) of Env is required for the incorporation of Env onto HIV particles in T cells and macrophages. Here we identify the Rab11a-FIP1C/RCP protein as an essential cofactor for HIV-1 Env incorporation onto particles in relevant human cells. Depletion of FIP1C reduced Env incorporation in a cytoplasmic tail-dependent manner, and was rescued by replenishment of FIP1C. FIP1C was redistributed out of the endosomal recycling complex to the plasma membrane by wild type Env protein but not by CT-truncated Env. Rab14 was required for HIV-1 Env incorporation, and FIP1C mutants incapable of binding Rab14 failed to rescue Env incorporation. Expression of FIP1C and Rab14 led to an enhancement of Env incorporation, indicating that these trafficking factors are normally limiting for CT-dependent Env incorporation onto particles. These findings support a model for HIV-1 Env incorporation in which specific targeting to the particle assembly microdomain on the plasma membrane is mediated by FIP1C and Rab14.",2013 Apr 4,"['Qi, Mingli', 'Williams, Janice A.', 'Chu, Hin', 'Chen, Xuemin', 'Wang, Jaang-Jiun', 'Ding, Lingmei', 'Akhirome, Ehiole', 'Wen, Xiaoyun', 'Lapierre, Lynne A.', 'Goldenring, James R.', 'Spearman, Paul']",PLoS Pathog,,,True
4278a9b763f17829897dde88a49fcab6ab86b8c7,PMC,Alginic Acid-Coated Chitosan Nanoparticles Loaded with Legumain DNA Vaccine: Effect against Breast Cancer in Mice,http://dx.doi.org/10.1371/journal.pone.0060190,PMC3618226,23577091,CC BY,"Legumain-based DNA vaccines have potential to protect against breast cancer. However, the lack of a safe and efficient oral delivery system restricts its clinical application. Here, we constructed alginic acid-coated chitosan nanoparticles (A.C.NPs) as an oral delivery carrier for a legumain DNA vaccine. First, we tested its characteristic in acidic environments in vitro. DNA agarose electrophoresis data show that A.C.NPs protected DNA better from degradation in acidic solution (pH 1.5) than did chitosan nanoparticles (C.NPs). Furthermore, size distribution analysis showed that A.C.NPs tended to aggregate and form micrometer scale complexes in pH<2.7, while dispersing into nanoparticles with an increase in pH. Mice were intragastrically administrated A.C.NPs carrying EGFP plasmids and EGFP expression was detected in the intestinal Peyer’s patches. Full-length legumain plasmids were loaded into different delivery carriers, including C.NPs, attenuated Salmonella typhimurium and A.C.NPs. A.C.NPs loaded with empty plasmids served as a control. Oral vaccination was performed in the murine orthotopic 4T1 breast cancer model. Our data indicate that tumor volume was significantly smaller in groups using A.C.NPs or attenuated Salmonella typhimurium as carriers. Furthermore, splenocytes co-cultured them with 4T1 cells pre-stimulated with CoCl(2), which influenced the translocation of legumain from cytoplasm to plasma membrane, showed a 4.7 and 2.3 folds increase in active cytotoxic T lymphocytes (CD3(+)/CD8(+)/CD25(+)) when treated with A.C.NPs carriers compared with PBS C.NPs. Our study suggests that C.NPs coated with alginic acid may be a safe and efficient tool for oral delivery of a DNA vaccine. Moreover, a legumain DNA vaccine delivered orally with A.C.NPs can effectively improve autoimmune response and protect against breast cancer in mice.",2013 Apr 5,"['Liu, Ze', 'Lv, Dan', 'Liu, Shu', 'Gong, Junbo', 'Wang, Da', 'Xiong, Min', 'Chen, Xiaoniao', 'Xiang, Rong', 'Tan, Xiaoyue']",PLoS One,,,True
c296f6a98b4eb94a69e4caef2df38ccf6e498511,PMC,Pathogenic mechanisms implicated in the intravascular coagulation in the lungs of BVDV-infected calves challenged with BHV-1,http://dx.doi.org/10.1186/1297-9716-44-20,PMC3618313,23506546,CC BY,"Resistance to respiratory disease in cattle requires host defense mechanisms that protect against pathogens which have evolved sophisticated strategies to evade them, including an altered function of pulmonary macrophages (MΦs) or the induction of inflammatory responses that cause lung injury and sepsis. The aim of this study was to clarify the mechanisms responsible for vascular changes occurring in the lungs of calves infected with bovine viral diarrhea virus (BVDV) and challenged later with bovine herpesvirus type 1 (BHV-1), evaluating the role of MΦs in the development of pathological lesions in this organ. For this purpose, pulmonary lesions were compared between co-infected calves and healthy animals inoculated only with BHV-1 through immunohistochemical (MAC387, TNFα, IL-1α, iNOS, COX-2 and Factor-VIII) and ultrastructural studies. Both groups of calves presented important vascular alterations produced by fibrin microthrombi and platelet aggregations within the blood vessels. These findings were earlier and more severe in the co-infected group, indicating that the concomitance of BVDV and BHV-1 in the lungs disrupts the pulmonary homeostasis by facilitating the establishment of an inflammatory and procoagulant environment modulated by inflammatory mediators released by pulmonary MΦs. In this regard, the co-infected calves, in spite of presenting a greater number of IMΦs than single-infected group, show a significant decrease in iNOS expression coinciding with the presence of more coagulation lesions. Moreover, animals pre-inoculated with BVDV displayed an alteration in the response of pro-inflammatory cytokines (TNFα and IL-1), which play a key role in activating the immune response, as well as in the local cell-mediated response.",2013 Mar 18,"['Risalde, María A', 'Molina, Verónica', 'Sánchez-Cordón, Pedro J', 'Romero-Palomo, Fernando', 'Pedrera, Miriam', 'Garfia, Bartolomé', 'Gómez-Villamandos, José C']",Vet Res,,,True
055ed1f10bcc96eacefe967b946a0b8c1674e197,PMC,Absence of CCR5 increases neutrophil recruitment in severe herpetic encephalitis,http://dx.doi.org/10.1186/1471-2202-14-19,PMC3618319,23391218,CC BY,"BACKGROUND: The neuroinflammatory response aimed at clearance of herpes simplex virus-1 (HSV-1) plays a key role in the pathogenesis of neuroaxonal damage in herpetic encephalitis. Leukocytes activated in an adaptive immune response access brain tissue by passing through the blood–brain barrier. The chemokine CCL5/RANTES is involved in recruitment of these cells to the brain acting via the receptors CCR1, CCR3 and mainly CCR5. Here, we evaluated the role of CCR5 on traffic of leukocytes in the brain microvasculature, cellular and cytokines profile in a severe form of herpetic encephalitis. RESULTS: Wild type and mice lacking CCR5 (CCR5(-/-)) were inoculated intracerebrally with 10(4) PFU of neurotropic HSV-1. We evaluated the traffic of leukocytes in the brain microvasculature using intravital microscopy and the profile of cytokines by Enzyme-Linked Immunosorbent Assay at 1 day post infection. Flow cytometry and histopathological analyses were also carried out in brain tissue. Absence of CCR5 leads to lower viral load and an increased leukocyte adhesion in brain microvasculature, predominantly of neutrophils (CD11(+) Ly6G(+) cells). Moreover, there was a significant increase in the levels of MIP-1/CCL2, RANTES/CCL5, KC/CXCL1 and MIG/CXCL9 in the brain of infected CCR5(-/-) mice. CONCLUSIONS: These results suggest that the absence of CCR5 may boost the immune response with a high neutrophil recruitment which most likely helps in viral clearance. Nonetheless, the elevated immune response may be detrimental to the host.",2013 Feb 7,"['Vilela, Márcia Carvalho', 'Lima, Graciela Kunrath', 'Rodrigues, David Henrique', 'Lacerda-Queiroz, Norinne', 'Pedroso, Vinicius Sousa Pietra', 'Miranda, Aline Silva', 'Rachid, Milene Alvarenga', 'Kroon, Erna Geessien', 'Campos, Marco Antônio', 'Teixeira, Mauro Martins', 'Sellner, Johann', 'Teixeira, Antonio Lucio']",BMC Neurosci,,,True
feaab7f92856f7b66f9e069f2686bc90660e9029,PMC,Multicomponent Therapeutics of Berberine Alkaloids,http://dx.doi.org/10.1155/2013/545898,PMC3619540,23634170,CC BY,"Although berberine alkaloids (BAs) are reported to be with broad-spectrum antibacterial and antiviral activities, the interactions among BAs have not been elucidated. In the present study, methicillin-resistant Staphylococcus aureus (MRSA) was chosen as a model organism, and modified broth microdilution was applied for the determination of the fluorescence absorption values to calculate the anti-MRSA activity of BAs. We have initiated four steps to seek the optimal combination of BAs that are (1) determining the anti-MRSA activity of single BA, (2) investigating the two-component combination to clarify the interactions among BAs by checkerboard assay, (3) investigating the multicomponent combination to determine the optimal ratio by quadratic rotation-orthogonal combination design, and (4) in vivo and in vitro validation of the optimal combination. The results showed that the interactions among BAs are related to their concentrations. The synergetic combinations included “berberine and epiberberine,” “jatrorrhizine and palmatine” and “jatrorrhizine and coptisine”; the antagonistic combinations included “coptisine and epiberberine”. The optimal combination was berberine : coptisine : jatrorrhizine : palmatine : epiberberine = 0.702 : 0.863 : 1 : 0.491 : 0.526, and the potency of the optimal combination on cyclophosphamide-immunocompromised mouse model was better than the natural combinations of herbs containing BAs.",2013 Mar 24,"['Luo, Jiaoyang', 'Yan, Dan', 'Yang, Meihua', 'Dong, Xiaoping', 'Xiao, Xiaohe']",Evid Based Complement Alternat Med,,,True
91781004fcf2142034de62e1212be3d885139060,PMC,"Using GPS Technology to Quantify Human Mobility, Dynamic Contacts and Infectious Disease Dynamics in a Resource-Poor Urban Environment",http://dx.doi.org/10.1371/journal.pone.0058802,PMC3620113,23577059,CC BY,"Empiric quantification of human mobility patterns is paramount for better urban planning, understanding social network structure and responding to infectious disease threats, especially in light of rapid growth in urbanization and globalization. This need is of particular relevance for developing countries, since they host the majority of the global urban population and are disproportionally affected by the burden of disease. We used Global Positioning System (GPS) data-loggers to track the fine-scale (within city) mobility patterns of 582 residents from two neighborhoods from the city of Iquitos, Peru. We used ∼2.3 million GPS data-points to quantify age-specific mobility parameters and dynamic co-location networks among all tracked individuals. Geographic space significantly affected human mobility, giving rise to highly local mobility kernels. Most (∼80%) movements occurred within 1 km of an individual’s home. Potential hourly contacts among individuals were highly irregular and temporally unstructured. Only up to 38% of the tracked participants showed a regular and predictable mobility routine, a sharp contrast to the situation in the developed world. As a case study, we quantified the impact of spatially and temporally unstructured routines on the dynamics of transmission of an influenza-like pathogen within an Iquitos neighborhood. Temporally unstructured daily routines (e.g., not dominated by a single location, such as a workplace, where an individual repeatedly spent significant amount of time) increased an epidemic’s final size and effective reproduction number by 20% in comparison to scenarios modeling temporally structured contacts. Our findings provide a mechanistic description of the basic rules that shape human mobility within a resource-poor urban center, and contribute to the understanding of the role of fine-scale patterns of individual movement and co-location in infectious disease dynamics. More generally, this study emphasizes the need for careful consideration of human social interactions when designing infectious disease mitigation strategies, particularly within resource-poor urban environments.",2013 Apr 8,"['Vazquez-Prokopec, Gonzalo M.', 'Bisanzio, Donal', 'Stoddard, Steven T.', 'Paz-Soldan, Valerie', 'Morrison, Amy C.', 'Elder, John P.', 'Ramirez-Paredes, Jhon', 'Halsey, Eric S.', 'Kochel, Tadeusz J.', 'Scott, Thomas W.', 'Kitron, Uriel']",PLoS One,,,True
7cd5321d8b9deb046502c0f1ab1581e7200bc378,PMC,DNA Vaccine Delivered by a Needle-Free Injection Device Improves Potency of Priming for Antibody and CD8+ T-Cell Responses after rAd5 Boost in a Randomized Clinical Trial,http://dx.doi.org/10.1371/journal.pone.0059340,PMC3620125,23577062,CC0,"BACKGROUND: DNA vaccine immunogenicity has been limited by inefficient delivery. Needle-free delivery of DNA using a CO(2)-powered Biojector® device was compared to delivery by needle and syringe and evaluated for safety and immunogenicity. METHODS: Forty adults, 18–50 years, were randomly assigned to intramuscular (IM) vaccinations with DNA vaccine, VRC-HIVDNA016-00-VP, (weeks 0, 4, 8) by Biojector® 2000™ or needle and syringe (N/S) and boosted IM at week 24 with VRC-HIVADV014-00-VP (rAd5) with N/S at 10(10) or 10(11) particle units (PU). Equal numbers per assigned schedule had low (≤500) or high (>500) reciprocal titers of preexisting Ad5 neutralizing antibody. RESULTS: 120 DNA and 39 rAd5 injections were given; 36 subjects completed follow-up research sample collections. IFN-γ ELISpot response rates were 17/19 (89%) for Biojector® and 13/17 (76%) for N/S delivery at Week 28 (4 weeks post rAd5 boost). The magnitude of ELISpot response was about 3-fold higher in Biojector® compared to N/S groups. Similar effects on response rates and magnitude were observed for CD8+, but not CD4+ T-cell responses by ICS. Env-specific antibody responses were about 10-fold higher in Biojector-primed subjects. CONCLUSIONS: DNA vaccination by Biojector® was well-tolerated and compared to needle injection, primed for greater IFN-γ ELISpot, CD8+ T-cell, and antibody responses after rAd5 boosting. TRIAL REGISTRATION: ClinicalTrials.gov NCT00109629",2013 Apr 8,"['Graham, Barney S.', 'Enama, Mary E.', 'Nason, Martha C.', 'Gordon, Ingelise J.', 'Peel, Sheila A.', 'Ledgerwood, Julie E.', 'Plummer, Sarah A.', 'Mascola, John R.', 'Bailer, Robert T.', 'Roederer, Mario', 'Koup, Richard A.', 'Nabel, Gary J.', None]",PLoS One,,,True
a2f53651474ffa6ede94371fa2d2e735395d965e,PMC,DNA Vaccine Delivered by a Needle-Free Injection Device Improves Potency of Priming for Antibody and CD8+ T-Cell Responses after rAd5 Boost in a Randomized Clinical Trial,http://dx.doi.org/10.1371/journal.pone.0059340,PMC3620125,23577062,CC0,"BACKGROUND: DNA vaccine immunogenicity has been limited by inefficient delivery. Needle-free delivery of DNA using a CO(2)-powered Biojector® device was compared to delivery by needle and syringe and evaluated for safety and immunogenicity. METHODS: Forty adults, 18–50 years, were randomly assigned to intramuscular (IM) vaccinations with DNA vaccine, VRC-HIVDNA016-00-VP, (weeks 0, 4, 8) by Biojector® 2000™ or needle and syringe (N/S) and boosted IM at week 24 with VRC-HIVADV014-00-VP (rAd5) with N/S at 10(10) or 10(11) particle units (PU). Equal numbers per assigned schedule had low (≤500) or high (>500) reciprocal titers of preexisting Ad5 neutralizing antibody. RESULTS: 120 DNA and 39 rAd5 injections were given; 36 subjects completed follow-up research sample collections. IFN-γ ELISpot response rates were 17/19 (89%) for Biojector® and 13/17 (76%) for N/S delivery at Week 28 (4 weeks post rAd5 boost). The magnitude of ELISpot response was about 3-fold higher in Biojector® compared to N/S groups. Similar effects on response rates and magnitude were observed for CD8+, but not CD4+ T-cell responses by ICS. Env-specific antibody responses were about 10-fold higher in Biojector-primed subjects. CONCLUSIONS: DNA vaccination by Biojector® was well-tolerated and compared to needle injection, primed for greater IFN-γ ELISpot, CD8+ T-cell, and antibody responses after rAd5 boosting. TRIAL REGISTRATION: ClinicalTrials.gov NCT00109629",2013 Apr 8,"['Graham, Barney S.', 'Enama, Mary E.', 'Nason, Martha C.', 'Gordon, Ingelise J.', 'Peel, Sheila A.', 'Ledgerwood, Julie E.', 'Plummer, Sarah A.', 'Mascola, John R.', 'Bailer, Robert T.', 'Roederer, Mario', 'Koup, Richard A.', 'Nabel, Gary J.', None]",PLoS One,,,True
ca0cc9c9da1307a7f36276eea4d117d6f74c2d7f,PMC,Attenuation of Mouse Hepatitis Virus by Deletion of the LLRKxGxKG Region of Nsp1,http://dx.doi.org/10.1371/journal.pone.0061166,PMC3620170,23593419,CC BY,"Coronaviruses are a family of large positive-sense RNA viruses that are responsible for a wide range of important veterinary and human diseases. Nsp1 has been shown to have an important role in the pathogenetic mechanisms of coronaviruses in vivo. To assess the function of a relatively conserved domain (LLRKxGxKG) of MHV nsp1, a mutant virus, MHV-nsp1-27D, with a 27 nts (LLRKxGxKG) deletion in nsp1, was constructed using a reverse genetic system with a vaccinia virus vector. The mutant virus had similar growth kinetics to MHV-A59 wild-type virus in 17CI-1 cells, but was highly attenuated in vivo. Moreover, the mutant virus completely protected C57BL/6 mice from a lethal MHV-A59 challenge. To further analyze the mechanism of the attenuation of the mutant virus, changes in reporter gene expression were measured in nsp1- or nsp1-27D-expressing cells; the results showed that nsp1 inhibited reporter gene expression controlled by different promoters, but that this inhibition was reduced for nsp1-27D. The research in vivo and in vitro suggests that the LLRKxGxKG region of nsp1 may play an important role in this process.",2013 Apr 8,"['Lei, Lin', 'Ying, Sun', 'Baojun, Luo', 'Yi, Yang', 'Xiang, He', 'Wenli, Su', 'Zounan, Sun', 'Deyin, Guo', 'Qingyu, Zhu', 'Jingmei, Liu', 'Guohui, Chang']",PLoS One,,,True
6b810552f81fc62a9f69f64033011fd5c627c8ea,PMC,Identification of diverse full-length endogenous betaretroviruses in megabats and microbats,http://dx.doi.org/10.1186/1742-4690-10-35,PMC3621094,23537098,CC BY,"BACKGROUND: Betaretroviruses infect a wide range of species including primates, rodents, ruminants, and marsupials. They exist in both endogenous and exogenous forms and are implicated in animal diseases such as lung cancer in sheep, and in human disease, with members of the human endogenous retrovirus-K (HERV-K) group of endogenous betaretroviruses (βERVs) associated with human cancers and autoimmune diseases. To improve our understanding of betaretroviruses in an evolutionarily distinct host species, we characterized βERVs present in the genomes and transcriptomes of mega- and microbats, which are an important reservoir of emerging viruses. RESULTS: A diverse range of full-length βERVs were discovered in mega- and microbat genomes and transcriptomes including the first identified intact endogenous retrovirus in a bat. Our analysis revealed that the genus Betaretrovirus can be divided into eight distinct sub-groups with evidence of cross-species transmission. Betaretroviruses are revealed to be a complex retrovirus group, within which one sub-group has evolved from complex to simple genomic organization through the acquisition of an env gene from the genus Gammaretrovirus. Molecular dating suggests that bats have contended with betaretroviral infections for over 30 million years. CONCLUSIONS: Our study reveals that a diverse range of betaretroviruses have circulated in bats for most of their evolutionary history, and cluster with extant betaretroviruses of divergent mammalian lineages suggesting that their distribution may be largely unrestricted by host species barriers. The presence of βERVs with the ability to transcribe active viral elements in a major animal reservoir for viral pathogens has potential implications for public health.",2013 Mar 27,"['Hayward, Joshua A', 'Tachedjian, Mary', 'Cui, Jie', 'Field, Hume', 'Holmes, Edward C', 'Wang, Lin-Fa', 'Tachedjian, Gilda']",Retrovirology,,,True
f50e4c99f7dcf23d79095c8d45048edf342e8db4,PMC,Identification of diverse full-length endogenous betaretroviruses in megabats and microbats,http://dx.doi.org/10.1186/1742-4690-10-35,PMC3621094,23537098,CC BY,"BACKGROUND: Betaretroviruses infect a wide range of species including primates, rodents, ruminants, and marsupials. They exist in both endogenous and exogenous forms and are implicated in animal diseases such as lung cancer in sheep, and in human disease, with members of the human endogenous retrovirus-K (HERV-K) group of endogenous betaretroviruses (βERVs) associated with human cancers and autoimmune diseases. To improve our understanding of betaretroviruses in an evolutionarily distinct host species, we characterized βERVs present in the genomes and transcriptomes of mega- and microbats, which are an important reservoir of emerging viruses. RESULTS: A diverse range of full-length βERVs were discovered in mega- and microbat genomes and transcriptomes including the first identified intact endogenous retrovirus in a bat. Our analysis revealed that the genus Betaretrovirus can be divided into eight distinct sub-groups with evidence of cross-species transmission. Betaretroviruses are revealed to be a complex retrovirus group, within which one sub-group has evolved from complex to simple genomic organization through the acquisition of an env gene from the genus Gammaretrovirus. Molecular dating suggests that bats have contended with betaretroviral infections for over 30 million years. CONCLUSIONS: Our study reveals that a diverse range of betaretroviruses have circulated in bats for most of their evolutionary history, and cluster with extant betaretroviruses of divergent mammalian lineages suggesting that their distribution may be largely unrestricted by host species barriers. The presence of βERVs with the ability to transcribe active viral elements in a major animal reservoir for viral pathogens has potential implications for public health.",2013 Mar 27,"['Hayward, Joshua A', 'Tachedjian, Mary', 'Cui, Jie', 'Field, Hume', 'Holmes, Edward C', 'Wang, Lin-Fa', 'Tachedjian, Gilda']",Retrovirology,,,False
cc74f79668feafbc452602e7de4304aec2d411b6,PMC,Identification of diverse full-length endogenous betaretroviruses in megabats and microbats,http://dx.doi.org/10.1186/1742-4690-10-35,PMC3621094,23537098,CC BY,"BACKGROUND: Betaretroviruses infect a wide range of species including primates, rodents, ruminants, and marsupials. They exist in both endogenous and exogenous forms and are implicated in animal diseases such as lung cancer in sheep, and in human disease, with members of the human endogenous retrovirus-K (HERV-K) group of endogenous betaretroviruses (βERVs) associated with human cancers and autoimmune diseases. To improve our understanding of betaretroviruses in an evolutionarily distinct host species, we characterized βERVs present in the genomes and transcriptomes of mega- and microbats, which are an important reservoir of emerging viruses. RESULTS: A diverse range of full-length βERVs were discovered in mega- and microbat genomes and transcriptomes including the first identified intact endogenous retrovirus in a bat. Our analysis revealed that the genus Betaretrovirus can be divided into eight distinct sub-groups with evidence of cross-species transmission. Betaretroviruses are revealed to be a complex retrovirus group, within which one sub-group has evolved from complex to simple genomic organization through the acquisition of an env gene from the genus Gammaretrovirus. Molecular dating suggests that bats have contended with betaretroviral infections for over 30 million years. CONCLUSIONS: Our study reveals that a diverse range of betaretroviruses have circulated in bats for most of their evolutionary history, and cluster with extant betaretroviruses of divergent mammalian lineages suggesting that their distribution may be largely unrestricted by host species barriers. The presence of βERVs with the ability to transcribe active viral elements in a major animal reservoir for viral pathogens has potential implications for public health.",2013 Mar 27,"['Hayward, Joshua A', 'Tachedjian, Mary', 'Cui, Jie', 'Field, Hume', 'Holmes, Edward C', 'Wang, Lin-Fa', 'Tachedjian, Gilda']",Retrovirology,,,False
928c0266f9fede929216a7c6f3370d32ff638401,PMC,Virological and clinical characterizations of respiratory infections in hospitalized children,http://dx.doi.org/10.1186/1824-7288-39-22,PMC3621398,23536956,CC BY,"BACKGROUND: The purpose of this study was to determine the incidence and seasonal distribution of viral etiological agents and to compare their clinical manifestations and disease severity, including single and co infections. METHODS: Multiplex reverse-transcription PCR was performed for the detection of viruses in nasopharyngeal aspirat. Disease severity was grouped using a categorization index as very mild/mild, and moderate/severe. Clinical and laboratory characteristics of hospitalized children with viral respiratory tract infection were analyzed. RESULTS: Viral pathogens were detected in 103/155 (66.5%) of patients. In order of frequency, identified pathogens were respiratory syncytial virus (32.0%), adenovirus (26.2%), parainfluenza viruses type 1–4 (19.4%), rhinovirus (18.4%), influenza A and B (12.6%), human metapneumovirus (12.6%), coronavirus (2.9%), and bocavirus (0.9%). Coinfections were present in 21 samples. Most of the children had very mild (38.8%) and mild disease (37.9%). Severity of illness was not worse with coinfections. The most common discharge diagnoses were ""URTI"" with or without LRTI/asthma (n=58). Most viruses exhibited strong seasonal patterns. Leukocytosis (22.2%) and neutrophilia (36.6%) were most commonly detected in patients with adenovirus and rhinovirus (p<0.05). Monocytosis was the most remarkable finding in the patients (n=48, 53.3%), especially in patients with adenovirus (p<0.05). CONCLUSIONS: RSV and RhV were associated with higher severity of illness in hospitalized children. RSV found to account for half of LRTI hospitalizations. In AdV and FluA and B infections, fever lasted longer than in other viruses. Coinfections were detected in 21 of the patients. The presence of coinfections was not associated with increased disease severity.",2013 Mar 27,"['Bicer, Suat', 'Giray, Tuba', 'Çöl, Defne', 'Erdağ, Gülay Çiler', 'Vitrinel, Ayça', 'Gürol, Yesim', 'Çelik, Gülden', 'Kaspar, Çigdem', 'Küçük, Öznur']",Ital J Pediatr,,,True
cd06185d94b38abd3c8209a45897a589da964bf2,PMC,De novo Sequence Assembly and Characterization of Lycoris aurea Transcriptome Using GS FLX Titanium Platform of 454 Pyrosequencing,http://dx.doi.org/10.1371/journal.pone.0060449,PMC3621892,23593220,CC BY,"BACKGROUND: Lycoris aurea, also called Golden Magic Lily, is an ornamentally and medicinally important species of the Amaryllidaceae family. To date, the sequencing of its whole genome is unavailable as a non-model organism. Transcriptomic information is also scarce for this species. In this study, we performed de novo transcriptome sequencing to produce the first comprehensive expressed sequence tag (EST) dataset for L. aurea using high-throughput sequencing technology. METHODOLOGY AND PRINCIPAL FINDINGS: Total RNA was isolated from leaves with sodium nitroprusside (SNP), salicylic acid (SA), or methyl jasmonate (MeJA) treatment, stems, and flowers at the bud, blooming, and wilting stages. Equal quantities of RNA from each tissue and stage were pooled to construct a cDNA library. Using 454 pyrosequencing technology, a total of 937,990 high quality reads (308.63 Mb) with an average read length of 329 bp were generated. Clustering and assembly of these reads produced a non-redundant set of 141,111 unique sequences, comprising 24,604 contigs and 116,507 singletons. All of the unique sequences were involved in the biological process, cellular component and molecular function categories by GO analysis. Potential genes and their functions were predicted by KEGG pathway mapping and COG analysis. Based on our sequence analysis and published literatures, many putative genes involved in Amaryllidaceae alkaloids synthesis, including PAL, TYDC OMT, NMT, P450, and other potentially important candidate genes, were identified for the first time in this Lycoris. Furthermore, 6,386 SSRs and 18,107 high-confidence SNPs were identified in this EST dataset. CONCLUSIONS: The transcriptome provides an invaluable new data for a functional genomics resource and future biological research in L. aurea. The molecular markers identified in this study will provide a material basis for future genetic linkage and quantitative trait loci analyses, and will provide useful information for functional genomic research in future.",2013 Apr 9,"['Wang, Ren', 'Xu, Sheng', 'Jiang, Yumei', 'Jiang, Jingwei', 'Li, Xiaodan', 'Liang, Lijian', 'He, Jia', 'Peng, Feng', 'Xia, Bing']",PLoS One,,,True
a21f16327c9af00dfc25321123ac2a5b6eb7f690,PMC,Clinical Characteristics and Outcomes in Hospitalized Patients with Respiratory Viral Co-Infection during the 2009 H1N1 Influenza Pandemic,http://dx.doi.org/10.1371/journal.pone.0060845,PMC3622008,23585856,CC BY,"BACKGROUND: The clinical consequences of co-infection with two or more respiratory viruses are poorly understood. We sought to determine if co-infection with pandemic 2009–2010 influenza A H1N1 (pH1N1) and another respiratory virus was associated with worse clinical outcomes. METHODS: A retrospective cohort study was performed of all hospitalized patients with a positive respiratory viral panel (RVP) for two or more viruses within 72 hours of admission at our institution from October 2009 to December 2009. We compared patients infected with one respiratory virus to those with respiratory viral co-infection. RESULTS: We identified 617 inpatients with a positive RVP sample with a single virus and 49 inpatients with a positive RVP sample for two viruses (i.e. co-infection). Co-infected patients were significantly younger, more often had fever/chills, tachypnea, and they more often demonstrated interstitial opacities suggestive of viral pneumonia on the presenting chest radiograph (OR 7.5, 95% CI 3.4–16.5). The likelihood of death, length of stay, and requirement for intensive care unit level of care were similar in both groups, but patients with any respiratory virus co-infection were more likely to experience complications, particularly treatment for a secondary bacterial pneumonia (OR 6.8, 95% CI 3.3–14.2). Patients co-infected with pH1N1 and another respiratory virus were more likely to present with chest radiograph changes suggestive of a viral pneumonia, compared to mono-infection with pH1N1 (OR 16.9, 95% CI 4.5–62.7). By logistic regression using mono-infection with non-PH1N1 viruses as the reference group, co-infection with pH1N1 was the strongest independent predictor of treatment for a secondary bacterial pneumonia (OR 17.8, 95% CI 6.7–47.1). CONCLUSION: Patients with viral co-infection, particularly with pH1N1, were more likely to have chest radiograph features compatible with a viral pneumonia and complications during their hospital course, particularly treatment for secondary bacterial pneumonia. Despite this, co-infection was not associated with ICU admission.",2013 Apr 9,"['Echenique, Ignacio A.', 'Chan, Philip A.', 'Chapin, Kimberle C.', 'Andrea, Sarah B.', 'Fava, Joseph L.', 'Mermel, Leonard A.']",PLoS One,,,True
ec9ad2ac0be589d617f25f1cfc349f644d1bebf1,PMC,Intrahost Diversity of Feline Coronavirus: A Consensus between the Circulating Virulent/Avirulent Strains and the Internal Mutation Hypotheses?,http://dx.doi.org/10.1155/2013/572325,PMC3622387,23589704,CC BY,"To evaluate the most controversial issue concerning current feline coronavirus (FCoV) virology, the coexisting hypotheses of the intrahost and interhost origins of feline infectious peritonitis virus (FIPV) in regard to the pathogenesis of feline infectious peritonitis (FIP), this study aimed to assess the molecular diversity of the membrane gene FCoVs in 190 samples from 10 cats with signs of FIP and in 5 faecal samples from cats without signs of FIP. All samples from the non-FIP cats and 25.26% of the samples from the FIP cats were positive for the FCoV membrane (M) gene. Mutations in this gene consisted of SNP changes randomly scattered among the sequences; few mutations resulted in amino acid changes. No geographic pattern was observed. Of the cats without FIP that harboured FECoV, the amino acid sequence identities for the M gene were 100% among cats (Cats 1–3) from the same cattery, and the overall sequence identity for the M gene was ≥91%. In one cat, two different lineages of FCoV, one enteric and one systemic, were found that segregated apart in the M gene tree. In conclusion, the in vivo mutation transition hypothesis and the circulating high virulent-low virulent FCoV hypothesis have been found to be plausible according to the results obtained from sequencing the M gene.",2013 Mar 27,"['Hora, Aline S.', 'Asano, Karen M.', 'Guerra, Juliana M.', 'Mesquita, Ramon G.', 'Maiorka, Paulo', 'Richtzenhain, Leonardo J.', 'Brandão, Paulo E.']",ScientificWorldJournal,,,True
825bf8562f3e44a02f8f2bcbf055586d42771f0a,PMC,The closterovirus-derived gene expression and RNA interference vectors as tools for research and plant biotechnology,http://dx.doi.org/10.3389/fmicb.2013.00083,PMC3622897,23596441,CC BY,"Important progress in understanding replication, interactions with host plants, and evolution of closteroviruses enabled engineering of several vectors for gene expression and virus-induced gene silencing. Due to the broad host range of closteroviruses, these vectors expanded vector applicability to include important woody plants such as citrus and grapevine. Furthermore, large closterovirus genomes offer genetic capacity and stability unrivaled by other plant viral vectors. These features provided immense opportunities for using closterovirus vectors for the functional genomics studies and pathogen control in economically valuable crops. This review briefly summarizes advances in closterovirus research during the last decade, explores the relationships between virus biology and vector design, and outlines the most promising directions for future application of closterovirus vectors.",2013 Apr 11,"['Dolja, Valerian V.', 'Koonin, Eugene V.']",Front Microbiol,,,True
d07d6b58460992a4530b7b24d66e8b3861036a50,PMC,Host Cell Entry of Respiratory Syncytial Virus Involves Macropinocytosis Followed by Proteolytic Activation of the F Protein,http://dx.doi.org/10.1371/journal.ppat.1003309,PMC3623752,23593008,CC BY,"Respiratory Syncytial Virus (RSV) is a highly pathogenic member of the Paramyxoviridae that causes severe respiratory tract infections. Reports in the literature have indicated that to infect cells the incoming viruses either fuse their envelope directly with the plasma membrane or exploit clathrin-mediated endocytosis. To study the entry process in human tissue culture cells (HeLa, A549), we used fluorescence microscopy and developed quantitative, FACS-based assays to follow virus binding to cells, endocytosis, intracellular trafficking, membrane fusion, and infection. A variety of perturbants were employed to characterize the cellular processes involved. We found that immediately after binding to cells RSV activated a signaling cascade involving the EGF receptor, Cdc42, PAK1, and downstream effectors. This led to a series of dramatic actin rearrangements; the cells rounded up, plasma membrane blebs were formed, and there was a significant increase in fluid uptake. If these effects were inhibited using compounds targeting Na(+)/H(+) exchangers, myosin II, PAK1, and other factors, no infection was observed. The RSV was rapidly and efficiently internalized by an actin-dependent process that had all hallmarks of macropinocytosis. Rather than fusing with the plasma membrane, the viruses thus entered Rab5-positive, fluid-filled macropinosomes, and fused with the membranes of these on the average 50 min after internalization. Rab5 was required for infection. To find an explanation for the endocytosis requirement, which is unusual among paramyxoviruses, we analyzed the fusion protein, F, and could show that, although already cleaved by a furin family protease once, it underwent a second, critical proteolytic cleavage after internalization. This cleavage by a furin-like protease removed a small peptide from the F1 subunits, and made the virus infectious.",2013 Apr 11,"['Krzyzaniak, Magdalena Anna', 'Zumstein, Michael Thomas', 'Gerez, Juan Atilio', 'Picotti, Paola', 'Helenius, Ari']",PLoS Pathog,,,True
94156e6941fe78191b5997cdeb10cb3fd06e1221,PMC,"Complete genome sequence of acute viral necrosis virus associated with massive mortality outbreaks in the Chinese scallop, Chlamys farreri",http://dx.doi.org/10.1186/1743-422X-10-110,PMC3623871,23566284,CC BY,"BACKGROUND: Acute viral necrosis virus (AVNV) is the causative agent of a serious disease resulting in high mortality in cultured Chinese scallops, Chlamys farreri. We have sequenced and analyzed the complete genome of AVNV. RESULTS: The AVNV genome is a linear, double-stranded DNA molecule of 210,993 bp with a nucleotide composition of 38.5% G + C. A total of 123 open reading frames were predicted to encode functional proteins, ranging from 41 to 1,878 amino acid residues. The DNA sequence of AVNV is 97% identical to that of ostreid herpesvirus 1 (OsHV-1), and the amino acid sequences of the encoded proteins of these two viruses are 94-100% identical. The genomic organization of AVNV is similar to that of OsHV-1, and consists of two unique regions (170.4 kb and 3.4 kb, respectively), each flanked by two inverted repeats (7.6 kb and 10.2 kb, respectively), with a third unique region (1.5 kb) situated between the two internal repeats. CONCLUSIONS: Our results indicate that AVNV is a variant of OsHV-1. The AVNV genome sequence provides information useful for understanding the evolution and divergence of OsHV-1 in marine molluscs.",2013 Apr 8,"['Ren, Weicheng', 'Chen, Haixia', 'Renault, Tristan', 'Cai, Yuyong', 'Bai, Changming', 'Wang, Chongming', 'Huang, Jie']",Virol J,,,True
cd18b402ae6cf0913a3a12aef3a8819964d8057e,PMC,Pig immune response to general stimulus and to porcine reproductive and respiratory syndrome virus infection: a meta-analysis approach,http://dx.doi.org/10.1186/1471-2164-14-220,PMC3623894,23552196,CC BY,"BACKGROUND: The availability of gene expression data that corresponds to pig immune response challenges provides compelling material for the understanding of the host immune system. Meta-analysis offers the opportunity to confirm and expand our knowledge by combining and studying at one time a vast set of independent studies creating large datasets with increased statistical power. In this study, we performed two meta-analyses of porcine transcriptomic data: i) scrutinized the global immune response to different challenges, and ii) determined the specific response to Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection. To gain an in-depth knowledge of the pig response to PRRSV infection, we used an original approach comparing and eliminating the common genes from both meta-analyses in order to identify genes and pathways specifically involved in the PRRSV immune response. The software Pointillist was used to cope with the highly disparate data, circumventing the biases generated by the specific responses linked to single studies. Next, we used the Ingenuity Pathways Analysis (IPA) software to survey the canonical pathways, biological functions and transcription factors found to be significantly involved in the pig immune response. We used 779 chips corresponding to 29 datasets for the pig global immune response and 279 chips obtained from 6 datasets for the pig response to PRRSV infection, respectively. RESULTS: The pig global immune response analysis showed interconnected canonical pathways involved in the regulation of translation and mitochondrial energy metabolism. Biological functions revealed in this meta-analysis were centred around translation regulation, which included protein synthesis, RNA-post transcriptional gene expression and cellular growth and proliferation. Furthermore, the oxidative phosphorylation and mitochondria dysfunctions, associated with stress signalling, were highly regulated. Transcription factors such as MYCN, MYC and NFE2L2 were found in this analysis to be potentially involved in the regulation of the immune response. The host specific response to PRRSV infection engendered the activation of well-defined canonical pathways in response to pathogen challenge such as TREM1, toll-like receptor and hyper-cytokinemia/ hyper-chemokinemia signalling. Furthermore, this analysis brought forth the central role of the crosstalk between innate and adaptive immune response and the regulation of anti-inflammatory response. The most significant transcription factor potentially involved in this analysis was HMGB1, which is required for the innate recognition of viral nucleic acids. Other transcription factors like interferon regulatory factors IRF1, IRF3, IRF5 and IRF8 were also involved in the pig specific response to PRRSV infection. CONCLUSIONS: This work reveals key genes, canonical pathways and biological functions involved in the pig global immune response to diverse challenges, including PRRSV infection. The powerful statistical approach led us to consolidate previous findings as well as to gain new insights into the pig immune response either to common stimuli or specifically to PRRSV infection.",2013 Apr 3,"['Badaoui, Bouabid', 'Tuggle, Christopher K', 'Hu, Zhiliang', 'Reecy, James M', 'Ait-Ali, Tahar', 'Anselmo, Anna', 'Botti, Sara']",BMC Genomics,,,True
75f36f193e2cbaa2f34b23bfc645dd441551bd51,PMC,The Impact of Model Building on the Transmission Dynamics under Vaccination: Observable (Symptom-Based) versus Unobservable (Contagiousness-Dependent) Approaches,http://dx.doi.org/10.1371/journal.pone.0062062,PMC3625221,23593507,CC BY,"BACKGROUND: The way we formulate a mathematical model of an infectious disease to capture symptomatic and asymptomatic transmission can greatly influence the likely effectiveness of vaccination in the presence of vaccine effect for preventing clinical illness. The present study aims to assess the impact of model building strategy on the epidemic threshold under vaccination. METHODOLOGY/PRINCIPAL FINDINGS: We consider two different types of mathematical models, one based on observable variables including symptom onset and recovery from clinical illness (hereafter, the “observable model”) and the other based on unobservable information of infection event and infectiousness (the “unobservable model”). By imposing a number of modifying assumptions to the observable model, we let it mimic the unobservable model, identifying that the two models are fully consistent only when the incubation period is identical to the latent period and when there is no pre-symptomatic transmission. We also computed the reproduction numbers with and without vaccination, demonstrating that the data generating process of vaccine-induced reduction in symptomatic illness is consistent with the observable model only and examining how the effective reproduction number is differently calculated by two models. CONCLUSIONS: To explicitly incorporate the vaccine effect in reducing the risk of symptomatic illness into the model, it is fruitful to employ a model that directly accounts for disease progression. More modeling studies based on observable epidemiological information are called for.",2013 Apr 12,"['Ejima, Keisuke', 'Aihara, Kazuyuki', 'Nishiura, Hiroshi']",PLoS One,,,True
145bb000d606bc2ea82e7e11f79363796bc9b7b1,PMC,Widespread Divergence of the CEACAM/PSG Genes in Vertebrates and Humans Suggests Sensitivity to Selection,http://dx.doi.org/10.1371/journal.pone.0061701,PMC3628338,23613906,CC BY,"In mammals, carcinoembryonic antigen cell adhesion molecules (CEACAMs) and pregnancy-specific glycoproteins (PSGs) play important roles in the regulation of pathogen transmission, tumorigenesis, insulin signaling turnover, and fetal–maternal interactions. However, how these genes evolved and to what extent they diverged in humans remain to be investigated specifically. Based on syntenic mapping of chordate genomes, we reveal that diverging homologs with a prototypic CEACAM architecture–including an extracellular domain with immunoglobulin variable and constant domain-like regions, and an intracellular domain containing ITAM motif–are present from cartilaginous fish to humans, but are absent in sea lamprey, cephalochordate or urochordate. Interestingly, the CEACAM/PSG gene inventory underwent radical divergence in various vertebrate lineages: from zero in avian species to dozens in therian mammals. In addition, analyses of genetic variations in human populations showed the presence of various types of copy number variations (CNVs) at the CEACAM/PSG locus. These copy number polymorphisms have 3–80% frequency in select populations, and encompass single to more than six PSG genes. Furthermore, we found that CEACAM/PSG genes contain a significantly higher density of nonsynonymous single nucleotide polymorphism (SNP) compared to the chromosome average, and many CEACAM/PSG SNPs exhibit high population differentiation. Taken together, our study suggested that CEACAM/PSG genes have had a more dynamic evolutionary history in vertebrates than previously thought. Given that CEACAM/PSGs play important roles in maternal–fetal interaction and pathogen recognition, these data have laid the groundwork for future analysis of adaptive CEACAM/PSG genotype-phenotypic relationships in normal and complicated pregnancies as well as other etiologies.",2013 Apr 16,"['Chang, Chia Lin', 'Semyonov, Jenia', 'Cheng, Po Jen', 'Huang, Shang Yu', 'Park, Jae Il', 'Tsai, Huai-Jen', 'Lin, Cheng-Yung', 'Grützner, Frank', 'Soong, Yung Kuei', 'Cai, James J.', 'Hsu, Sheau Yu Teddy']",PLoS One,,,True
a977a48fcb972ec87cd97bd7017fd08c1d3d9ca2,PMC,Widespread Divergence of the CEACAM/PSG Genes in Vertebrates and Humans Suggests Sensitivity to Selection,http://dx.doi.org/10.1371/journal.pone.0061701,PMC3628338,23613906,CC BY,"In mammals, carcinoembryonic antigen cell adhesion molecules (CEACAMs) and pregnancy-specific glycoproteins (PSGs) play important roles in the regulation of pathogen transmission, tumorigenesis, insulin signaling turnover, and fetal–maternal interactions. However, how these genes evolved and to what extent they diverged in humans remain to be investigated specifically. Based on syntenic mapping of chordate genomes, we reveal that diverging homologs with a prototypic CEACAM architecture–including an extracellular domain with immunoglobulin variable and constant domain-like regions, and an intracellular domain containing ITAM motif–are present from cartilaginous fish to humans, but are absent in sea lamprey, cephalochordate or urochordate. Interestingly, the CEACAM/PSG gene inventory underwent radical divergence in various vertebrate lineages: from zero in avian species to dozens in therian mammals. In addition, analyses of genetic variations in human populations showed the presence of various types of copy number variations (CNVs) at the CEACAM/PSG locus. These copy number polymorphisms have 3–80% frequency in select populations, and encompass single to more than six PSG genes. Furthermore, we found that CEACAM/PSG genes contain a significantly higher density of nonsynonymous single nucleotide polymorphism (SNP) compared to the chromosome average, and many CEACAM/PSG SNPs exhibit high population differentiation. Taken together, our study suggested that CEACAM/PSG genes have had a more dynamic evolutionary history in vertebrates than previously thought. Given that CEACAM/PSGs play important roles in maternal–fetal interaction and pathogen recognition, these data have laid the groundwork for future analysis of adaptive CEACAM/PSG genotype-phenotypic relationships in normal and complicated pregnancies as well as other etiologies.",2013 Apr 16,"['Chang, Chia Lin', 'Semyonov, Jenia', 'Cheng, Po Jen', 'Huang, Shang Yu', 'Park, Jae Il', 'Tsai, Huai-Jen', 'Lin, Cheng-Yung', 'Grützner, Frank', 'Soong, Yung Kuei', 'Cai, James J.', 'Hsu, Sheau Yu Teddy']",PLoS One,,,False
44f9f629bf4db860b1cbb1cce7f925d0f7d29b30,PMC,Regulation of the Epithelial Adhesion Molecule CEACAM1 Is Important for Palate Formation,http://dx.doi.org/10.1371/journal.pone.0061653,PMC3629100,23613893,CC BY,"Cleft palate results from a mixture of genetic and environmental factors and occurs when the bilateral palatal shelves fail to fuse. The objective of this study was to search for new genes involved in mouse palate formation. Gene expression of murine embryonic palatal tissue was analyzed at various developmental stages before, during, and after palate fusion using GeneChip® microarrays. Ceacam1 was one of the highly up-regulated genes during palate formation, and this was confirmed by quantitative real-time PCR. Immunohistochemical staining showed that CEACAM1 was present in prefusion palatal epithelium and was degraded during fusion. To investigate the developmental role of CEACAM1, function-blocking antibody was added to embryonic mouse palate in organ culture. Palatal fusion was inhibited by this function-blocking antibody. To investigate the subsequent developmental role of CEACAM1, we characterized Ceacam1-deficient (Ceacam1 (−/−)) mice. Epithelial cells persisted abnormally at the midline of the embryonic palate even on day E16.0, and palatal fusion was delayed in Ceacam1 (−/−) mice. TGFβ3 expression, apoptosis, and cell proliferation in palatal epithelium were not affected in the palate of Ceacam1(−/−)mice. However, CEACAM1 expression was retained in the remaining MEE of TGFβ-deficient mice. These results suggest that CEACAM1 has roles in the initiation of palatal fusion via epithelial cell adhesion.",2013 Apr 17,"['Mima, Junko', 'Koshino, Aya', 'Oka, Kyoko', 'Uchida, Hitoshi', 'Hieda, Yohki', 'Nohara, Kanji', 'Kogo, Mikihiko', 'Chai, Yang', 'Sakai, Takayoshi']",PLoS One,,,True
2e905d86f4b7a8cb748864eb560c6555816fb0f1,PMC,Identification of Hepatotropic Viruses from Plasma Using Deep Sequencing: A Next Generation Diagnostic Tool,http://dx.doi.org/10.1371/journal.pone.0060595,PMC3629200,23613733,CC BY,"We conducted an unbiased metagenomics survey using plasma from patients with chronic hepatitis B, chronic hepatitis C, autoimmune hepatitis (AIH), non-alcoholic steatohepatitis (NASH), and patients without liver disease (control). RNA and DNA libraries were sequenced from plasma filtrates enriched in viral particles to catalog virus populations. Hepatitis viruses were readily detected at high coverage in patients with chronic viral hepatitis B and C, but only a limited number of sequences resembling other viruses were found. The exception was a library from a patient diagnosed with hepatitis C virus (HCV) infection that contained multiple sequences matching GB virus C (GBV-C). Abundant GBV-C reads were also found in plasma from patients with AIH, whereas Torque teno virus (TTV) was found at high frequency in samples from patients with AIH and NASH. After taxonomic classification of sequences by BLASTn, a substantial fraction in each library, ranging from 35% to 76%, remained unclassified. These unknown sequences were assembled into scaffolds along with virus, phage and endogenous retrovirus sequences and then analyzed by BLASTx against the non-redundant protein database. Nearly the full genome of a heretofore-unknown circovirus was assembled and many scaffolds that encoded proteins with similarity to plant, insect and mammalian viruses. The presence of this novel circovirus was confirmed by PCR. BLASTx also identified many polypeptides resembling nucleo-cytoplasmic large DNA viruses (NCLDV) proteins. We re-evaluated these alignments with a profile hidden Markov method, HHblits, and observed inconsistencies in the target proteins reported by the different algorithms. This suggests that sequence alignments are insufficient to identify NCLDV proteins, especially when these alignments are only to small portions of the target protein. Nevertheless, we have now established a reliable protocol for the identification of viruses in plasma that can also be adapted to other patient samples such as urine, bile, saliva and other body fluids.",2013 Apr 17,"['Law, John', 'Jovel, Juan', 'Patterson, Jordan', 'Ford, Glenn', 'O’keefe, Sandra', 'Wang, Weiwei', 'Meng, Bo', 'Song, Deyong', 'Zhang, Yong', 'Tian, Zhijian', 'Wasilenko, Shawn T.', 'Rahbari, Mandana', 'Mitchell, Troy', 'Jordan, Tracy', 'Carpenter, Eric', 'Mason, Andrew L.', 'Wong, Gane Ka-Shu']",PLoS One,,,True
de2ae20e4362e57c914f6bf1b9c51e0a4d90bfe1,PMC,Identification of Hepatotropic Viruses from Plasma Using Deep Sequencing: A Next Generation Diagnostic Tool,http://dx.doi.org/10.1371/journal.pone.0060595,PMC3629200,23613733,CC BY,"We conducted an unbiased metagenomics survey using plasma from patients with chronic hepatitis B, chronic hepatitis C, autoimmune hepatitis (AIH), non-alcoholic steatohepatitis (NASH), and patients without liver disease (control). RNA and DNA libraries were sequenced from plasma filtrates enriched in viral particles to catalog virus populations. Hepatitis viruses were readily detected at high coverage in patients with chronic viral hepatitis B and C, but only a limited number of sequences resembling other viruses were found. The exception was a library from a patient diagnosed with hepatitis C virus (HCV) infection that contained multiple sequences matching GB virus C (GBV-C). Abundant GBV-C reads were also found in plasma from patients with AIH, whereas Torque teno virus (TTV) was found at high frequency in samples from patients with AIH and NASH. After taxonomic classification of sequences by BLASTn, a substantial fraction in each library, ranging from 35% to 76%, remained unclassified. These unknown sequences were assembled into scaffolds along with virus, phage and endogenous retrovirus sequences and then analyzed by BLASTx against the non-redundant protein database. Nearly the full genome of a heretofore-unknown circovirus was assembled and many scaffolds that encoded proteins with similarity to plant, insect and mammalian viruses. The presence of this novel circovirus was confirmed by PCR. BLASTx also identified many polypeptides resembling nucleo-cytoplasmic large DNA viruses (NCLDV) proteins. We re-evaluated these alignments with a profile hidden Markov method, HHblits, and observed inconsistencies in the target proteins reported by the different algorithms. This suggests that sequence alignments are insufficient to identify NCLDV proteins, especially when these alignments are only to small portions of the target protein. Nevertheless, we have now established a reliable protocol for the identification of viruses in plasma that can also be adapted to other patient samples such as urine, bile, saliva and other body fluids.",2013 Apr 17,"['Law, John', 'Jovel, Juan', 'Patterson, Jordan', 'Ford, Glenn', 'O’keefe, Sandra', 'Wang, Weiwei', 'Meng, Bo', 'Song, Deyong', 'Zhang, Yong', 'Tian, Zhijian', 'Wasilenko, Shawn T.', 'Rahbari, Mandana', 'Mitchell, Troy', 'Jordan, Tracy', 'Carpenter, Eric', 'Mason, Andrew L.', 'Wong, Gane Ka-Shu']",PLoS One,,,False
5a4760a109394f2d59a82a5831c23ab7ac259eb2,PMC,Trends in North American Newspaper Reporting of Brain Injury in Ice Hockey,http://dx.doi.org/10.1371/journal.pone.0061865,PMC3629225,23613957,CC BY,"The frequency and potential long-term effects of sport-related traumatic brain injuries (TBI) make it a major public health concern. The culture within contact sports, such as ice hockey, encourages aggression that puts youth at risk of TBI such as concussion. Newspaper reports play an important role in conveying and shaping the culture around health-related behaviors. We qualitatively studied reports about sport-related TBI in four major North American newspapers over the last quarter-century. We used the grounded-theory approach to identify major themes and then did a content analysis to compare the frequency of key themes between 1998–2000 and 2009–2011. The major themes were: perceptions of brain injury, aggression, equipment, rules and regulations, and youth hockey. Across the full study period, newspaper articles from Canada and America portrayed violence and aggression that leads to TBI both as integral to hockey and as an unavoidable risk associated with playing the game. They also condemned violence in ice hockey, criticized the administrative response to TBI, and recognized the significance of TBI. In Canada, aggression was reported more often recently and there was a distinctive shift in portraying protective equipment as a solution to TBI in earlier years to a potential contributing factor to TBI later in the study period. American newspapers gave a greater attention to ‘perception of risks’ and the role of protective equipment, and discussed TBI in a broader context in the recent time period. Newspapers from both countries showed similar recent trends in regards to a need for rule changes to curb youth sport-related TBI. This study provides a rich description of the reporting around TBI in contact sport. Understanding this reporting is important for evaluating whether the dangers of sport-related TBI are being appropriately communicated by the media.",2013 Apr 17,"['Cusimano, Michael D.', 'Sharma, Bhanu', 'Lawrence, David W.', 'Ilie, Gabriela', 'Silverberg, Sarah', 'Jones, Rochelle']",PLoS One,,,True
7d9f6bae2b7ced5834b4e92e7ef805d85fdea405,PMC,Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus,http://dx.doi.org/10.1371/journal.pntd.0002181,PMC3630143,23638202,CC BY,"Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever.",2013 Apr 18,"['Lihoradova, Olga A.', 'Indran, Sabarish V.', 'Kalveram, Birte', 'Lokugamage, Nandadeva', 'Head, Jennifer A.', 'Gong, Bin', 'Tigabu, Bersabeh', 'Juelich, Terry L.', 'Freiberg, Alexander N.', 'Ikegami, Tetsuro']",PLoS Negl Trop Dis,,,True
d39202d51ca886b55a141cad30f55b5443395048,PMC,Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus,http://dx.doi.org/10.1371/journal.pntd.0002181,PMC3630143,23638202,CC BY,"Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever.",2013 Apr 18,"['Lihoradova, Olga A.', 'Indran, Sabarish V.', 'Kalveram, Birte', 'Lokugamage, Nandadeva', 'Head, Jennifer A.', 'Gong, Bin', 'Tigabu, Bersabeh', 'Juelich, Terry L.', 'Freiberg, Alexander N.', 'Ikegami, Tetsuro']",PLoS Negl Trop Dis,,,False
9fbfc291377589c67d526d29be532102bce9812f,PMC,Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus,http://dx.doi.org/10.1371/journal.pntd.0002181,PMC3630143,23638202,CC BY,"Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever.",2013 Apr 18,"['Lihoradova, Olga A.', 'Indran, Sabarish V.', 'Kalveram, Birte', 'Lokugamage, Nandadeva', 'Head, Jennifer A.', 'Gong, Bin', 'Tigabu, Bersabeh', 'Juelich, Terry L.', 'Freiberg, Alexander N.', 'Ikegami, Tetsuro']",PLoS Negl Trop Dis,,,False
bc2afee8129278e494059eee1c725462bc343456,PMC,Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus,http://dx.doi.org/10.1371/journal.pntd.0002181,PMC3630143,23638202,CC BY,"Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever.",2013 Apr 18,"['Lihoradova, Olga A.', 'Indran, Sabarish V.', 'Kalveram, Birte', 'Lokugamage, Nandadeva', 'Head, Jennifer A.', 'Gong, Bin', 'Tigabu, Bersabeh', 'Juelich, Terry L.', 'Freiberg, Alexander N.', 'Ikegami, Tetsuro']",PLoS Negl Trop Dis,,,False
6e4cbb8df1a37cf1dbcd398741b01accafde7c2b,PMC,Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus,http://dx.doi.org/10.1371/journal.pntd.0002181,PMC3630143,23638202,CC BY,"Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever.",2013 Apr 18,"['Lihoradova, Olga A.', 'Indran, Sabarish V.', 'Kalveram, Birte', 'Lokugamage, Nandadeva', 'Head, Jennifer A.', 'Gong, Bin', 'Tigabu, Bersabeh', 'Juelich, Terry L.', 'Freiberg, Alexander N.', 'Ikegami, Tetsuro']",PLoS Negl Trop Dis,,,False
d745e9cbecf81be30e9ffe290781acea84fbd9d3,PMC,The Development and Application of the Two Real-Time RT-PCR Assays to Detect the Pathogen of HFMD,http://dx.doi.org/10.1371/journal.pone.0061451,PMC3630163,23637836,CC BY,"Large-scale Hand, Foot, and Mouth Disease (HFMD) outbreaks have frequently occurred in China since 2008, affecting more than one million children and causing several hundred children deaths every year. The pathogens of HFMD are mainly human enteroviruses (HEVs). Among them, human enterovirus 71 (HEV71) and coxsackievirus A16 (CVA16) are the most common pathogens of HFMD. However, other HEVs could also cause HFMD. To rapidly detect HEV71 and CVA16, and ensure detection of all HEVs causing HFMD, two real-time hybridization probe-based RT-PCR assays were developed in this study. One is a multiplex real-time RT-PCR assay, which was developed to detect and differentiate HEV71 specifically from CVA16 directly from clinical specimens within 1–2 h, and the other is a broad-spectrum real-time RT-PCR assay, which targeted almost all HEVs. The experiments confirmed that the two assays have high sensitivity and specificity, and the sensitivity was up to 0.1 TCID(50)/ml for detection of HEVs, HEV71, and CVA16, respectively. A total of 213 clinical specimens were simultaneously detected by three kinds of assays, including the two real-time RT-PCR assays, direct conventional RT-PCR assay, and virus isolation assay on human rhabdomyosarcoma cells (RD cells). The total positive rate of both HEV71 and CVA16 was 69.48% with real-time RT-PCR assay, 47.42% with RT-PCR assay, and 34.58% with virus isolation assay. One HFMD clinical specimen was positive for HEV, but negative for HEV71 or CVA16, which was identified as Echovirus 11 (Echo11) by virus isolation, RT-PCR, and sequencing for the VP1 gene. The two real-time RT-PCR assays had been applied in 31 provincial HFMD labs to detect the pathogens of HFMD, which has contributed to the rapid identification of the pathogens in the early stages of HFMD outbreaks, and helped to clarify the etiologic agents of HFMD in China.",2013 Apr 18,"['Cui, Aili', 'Xu, Changping', 'Tan, Xiaojuan', 'Zhang, Yan', 'Zhu, Zhen', 'Mao, Naiying', 'Lu, Yiyu', 'Xu, Wenbo']",PLoS One,,,True
fbc5981e0920859187fee6c4243de58c9906f2ee,PMC,Complete Genome Sequence of a Recombinant Porcine Epidemic Diarrhea Virus Strain from Eastern China,http://dx.doi.org/10.1128/genomeA.00105-13,PMC3630398,23599287,CC BY,"A field porcine epidemic diarrhea virus (PEDV) strain, JS2008, was isolated from stool samples of a piglet with acute diarrhea on a vaccinated farm in eastern China. We sequenced and analyzed the complete genome of strain JS2008, which will help increase our understanding of the molecular characteristics of the epidemic PEDV in China.",2013 Apr 18,"['Li, Bin', 'Liu, Haofei', 'He, Kongwang', 'Guo, Rongli', 'Ni, Yanxiu', 'Du, Luping', 'Wen, Libin', 'Zhang, Xuehan', 'Yu, Zhengyu', 'Zhou, Junming', 'Mao, Aihua', 'Lv, Lixin', 'Hu, Yiyi', 'Yu, Yang', 'Zhu, Haodan', 'Wang, Xiaomin']",Genome Announc,,,True
707a1297b8ac950819a217102e5f4847a67b48c7,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,True
ecb3e7e1fdbb54d79d3b547fd4a4a44556c8f2f4,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
3695c79392a4adf72bfc7fa54125d3b5940967be,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
96c3708909d821152cedd5dff77196abcb2f2c92,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
52b222b674264d7e3d125dd0d36176b74642657e,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
9a5f67fedb2b14a2baf19e3b2cf2f6fff0ff7921,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
d2514e372c5ddf1d335efc9bca1e8d61b15df4cf,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
34fb3171b67b9a98bf2f5c6474d9fe6d5975a2bc,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
08dcd85ac15d14a2a14d1c81308ee516065282b0,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
966e2ff5e39796c7a3337620cb4167f780d18aea,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
5903202b5bdbfa366926099e3f46ed2fd6c65fef,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
40c76ef7831f3e2df1619e05514849a67a07d5d6,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,True
4ce340ef89eb6535f11ace1d627d98e619e2d17b,PMC,Virome Profiling of Bats from Myanmar by Metagenomic Analysis of Tissue Samples Reveals More Novel Mammalian Viruses,http://dx.doi.org/10.1371/journal.pone.0061950,PMC3632529,23630620,CC BY,"Bats are reservoir animals harboring many important pathogenic viruses and with the capability of transmitting these to humans and other animals. To establish an effective surveillance to monitor transboundary spread of bat viruses between Myanmar and China, complete organs from the thorax and abdomen from 853 bats of six species from two Myanmar counties close to Yunnan province, China, were collected and tested for their virome through metagenomics by Solexa sequencing and bioinformatic analysis. In total, 3,742,314 reads of 114 bases were generated, and over 86% were assembled into 1,649,512 contigs with an average length of 114 bp, of which 26,698 (2%) contigs were recognizable viral sequences belonging to 24 viral families. Of the viral contigs 45% (12,086/26,698) were related to vertebrate viruses, 28% (7,443/26,698) to insect viruses, 27% (7,074/26,698) to phages and 95 contigs to plant viruses. The metagenomic results were confirmed by PCR of selected viruses in all bat samples followed by phylogenetic analysis, which has led to the discovery of some novel bat viruses of the genera Mamastrovirus, Bocavirus, Circovirus, Iflavirus and Orthohepadnavirus and to their prevalence rates in two bat species. In conclusion, the present study aims to present the bat virome in Myanmar, and the results obtained further expand the spectrum of viruses harbored by bats.",2013 Apr 22,"['He, Biao', 'Li, Zuosheng', 'Yang, Fanli', 'Zheng, Junfeng', 'Feng, Ye', 'Guo, Huancheng', 'Li, Yingying', 'Wang, Yiyin', 'Su, Nan', 'Zhang, Fuqiang', 'Fan, Quanshui', 'Tu, Changchun']",PLoS One,,,True
fd990c95b7300a2e18a8be156f159943246e06b5,PMC,Citrus tristeza virus: Evolution of Complex and Varied Genotypic Groups,http://dx.doi.org/10.3389/fmicb.2013.00093,PMC3632782,23630519,CC BY,"Amongst the Closteroviridae, Citrus tristeza virus (CTV) is almost unique in possessing a number of distinct and characterized strains, isolates of which produce a wide range of phenotype combinations among its different hosts. There is little understanding to connect genotypes to phenotypes, and to complicate matters more, these genotypes are found throughout the world as members of mixed populations within a single host plant. There is essentially no understanding of how combinations of genotypes affect symptom expression and disease severity. We know little about the evolution of the genotypes that have been characterized to date, little about the biological role of their diversity and particularly, about the effects of recombination. Additionally, genotype grouping has not been standardized. In this study we utilized an extensive array of CTV genomic information to classify the major genotypes, and to determine the major evolutionary processes that led to their formation and subsequent retention. Our analyses suggest that three major processes act on these genotypes: (1) ancestral diversification of the major CTV lineages, followed by (2) conservation and co-evolution of the major functional domains within, though not between CTV genotypes, and (3) extensive recombination between lineages that have given rise to new genotypes that have subsequently been retained within the global population. The effects of genotype diversity and host-interaction are discussed, as is a proposal for standardizing the classification of existing and novel CTV genotypes.",2013 Apr 23,"Harper, S. J.",Front Microbiol,,,True
76d39ac4634db5a0fcc8cddbefd965c463c0ace0,PMC,"Decreased Pattern Recognition Receptor Signaling, Interferon-Signature, and Bactericidal/Permeability-Increasing Protein Gene Expression in Cord Blood of Term Low Birth Weight Human Newborns",http://dx.doi.org/10.1371/journal.pone.0062845,PMC3633842,23626859,CC BY,"BACKGROUND: Morbidity and mortality rates of low birth weight (LBW) newborns at term are higher than rates in normal birth weight (NBW) newborns. LBW newborns are at greater risk to acquire recurrent bacterial and viral infections during their first few weeks of life possibly as an outcome of compromised innate immune functions. As adaptive immunity is in a naive state, increased risk of infection of LBW as compared to NBW newborns may reflect impairments in innate immunity. METHODOLOGY: To characterize the increased susceptibility to infections in LBW newborns we used microarray technology to identify differences in gene expression in LBW newborns (n = 8) compared to NBW newborns (n = 4) using cord blood. The results obtained from the microarray study were validated on a larger number of samples using real time RT-PCR (LBW = 22, NBW = 18) and western blotting (LBW = 12, NBW = 12). The Interferome database was used to identify interferon (IFN) signature genes and ingenuity pathway analysis identified canonical pathways and biological functions associated with the differentially expressed genes in LBW newborns. ELISAs for IFNs and bactericidal/permeability-increasing protein were performed in both LBW and NBW newborns and in adults (LBW = 18, NBW = 18, Adults  = 8). PRINCIPAL FINDINGS: Upon microarray analysis, we identified 1,391 differentially expressed genes, of which, 1,065 genes were down-regulated and 326 genes were up-regulated in the LBW compared to NBW newborns. Of note, 70 IFN-signature genes were found to be significantly down-regulated in LBW compared to NBW newborns. Ingenuity pathway analysis revealed pattern recognition receptors signaling including Toll-Like Receptors (TLRs) -1, -5, and -8 genes and IFN signaling as the most significantly impacted pathways. Respiratory infectious diseases were the most significantly affected bio-functions in LBW newborns. CONCLUSION AND SIGNIFICANCE: Diminished PRRs, IFN-signature, and BPI gene expression raises the possibility that impairments in these pathways contribute to the susceptibility of LBW term infants to infection.",2013 Apr 23,"['Singh, Vikas Vikram', 'Chauhan, Sudhir Kumar', 'Rai, Richa', 'Kumar, Ashok', 'Singh, Shiva M.', 'Rai, Geeta']",PLoS One,,,True
1b3ea086b81a5e0c4dd22aa41653befc358d7163,PMC,Immunopathogenesis of Severe Acute Respiratory Disease in Zaire ebolavirus-Infected Pigs,http://dx.doi.org/10.1371/journal.pone.0061904,PMC3633953,23626748,CC BY,"Ebola viruses (EBOV) are filamentous single-stranded RNA viruses of the family Filoviridae. Zaire ebolavirus (ZEBOV) causes severe haemorrhagic fever in humans, great apes and non-human primates (NHPs) with high fatality rates. In contrast, Reston ebolavirus (REBOV), the only species found outside Africa, is lethal to some NHPs but has never been linked to clinical disease in humans despite documented exposure. REBOV was isolated from pigs in the Philippines and subsequent experiments confirmed the susceptibility of pigs to both REBOV and ZEBOV with predilection for the lungs. However, only ZEBOV caused severe lung pathology in 5–6 weeks old pigs leading to respiratory distress. To further elucidate the mechanisms for lung pathology, microarray analysis of changes in gene expression was performed on lung tissue from ZEBOV-infected pigs. Furthermore, systemic effects were monitored by looking at changes in peripheral blood leukocyte subsets and systemic cytokine responses. Following oro-nasal challenge, ZEBOV replicated mainly in the respiratory tract, causing severe inflammation of the lungs and consequently rapid and difficult breathing. Neutrophils and macrophages infiltrated the lungs but only the latter were positive for ZEBOV antigen. Genes for proinflammatory cytokines, chemokines and acute phase proteins, known to attract immune cells to sites of infection, were upregulated in the lungs, causing the heavy influx of cells into this site. Systemic effects included a decline in the proportion of monocyte/dendritic and B cells and a mild proinflammatory cytokine response. Serum IgM was detected on day 5 and 6 post infection. In conclusion, a dysregulation/over-activation of the pulmonary proinflammatory response may play a crucial role in the pathogenesis of ZEBOV infection in 5–6 weeks old pigs by attracting inflammatory cells to the lungs.",2013 Apr 23,"['Nfon, Charles K.', 'Leung, Anders', 'Smith, Greg', 'Embury-Hyatt, Carissa', 'Kobinger, Gary', 'Weingartl, Hana M.']",PLoS One,,,True
b55320e1004341c20c8b61cca6a2bb47c0dc4d59,PMC,9G DNAChip Technology: Self-Assembled Monolayer (SAM) of ssDNA for Ultra-Sensitive Detection of Biomarkers,http://dx.doi.org/10.3390/ijms14035723,PMC3634481,23481635,CC BY,"A 9G DNAChip obtained by allowing the formation of a self-assembled monolayer (SAM) of oligonucleotides appended with nine consecutive guanines on the chip surface has been applied in the detection of biomarkers. Using a 9G DNAChip, biomarker in the concentration range of 4 pg/mL to 40 fg/mL can be easily differentiated in the buffer matrix. Moreover, it is the first time that a biomarker with a concentration of 40 fg/mL has been detected in a mixture of proteins without use of any signal amplification technique.",2013 Mar 12,"['Nimse, Satish Balasaheb', 'Song, Keum-Soo', 'Kim, Junghoon', 'Sayyed, Danishmalik Rafiq', 'Kim, Taisun']",Int J Mol Sci,,,True
f2ed0201813317b17f4e6b34058b9a45a2ba8c63,PMC,9G DNAChip Technology: Self-Assembled Monolayer (SAM) of ssDNA for Ultra-Sensitive Detection of Biomarkers,http://dx.doi.org/10.3390/ijms14035723,PMC3634481,23481635,CC BY,"A 9G DNAChip obtained by allowing the formation of a self-assembled monolayer (SAM) of oligonucleotides appended with nine consecutive guanines on the chip surface has been applied in the detection of biomarkers. Using a 9G DNAChip, biomarker in the concentration range of 4 pg/mL to 40 fg/mL can be easily differentiated in the buffer matrix. Moreover, it is the first time that a biomarker with a concentration of 40 fg/mL has been detected in a mixture of proteins without use of any signal amplification technique.",2013 Mar 12,"['Nimse, Satish Balasaheb', 'Song, Keum-Soo', 'Kim, Junghoon', 'Sayyed, Danishmalik Rafiq', 'Kim, Taisun']",Int J Mol Sci,,,False
a0e91efcafa0a743be0342254943e8d31cd36558,PMC,A Study of the Mechanism of the Chaperone-like Function of an scFv of Human Creatine Kinase by Computer Simulation,http://dx.doi.org/10.1371/journal.pone.0062147,PMC3634753,23637984,CC BY,"A new application of antibodies is to use them as macromolecular chaperones. Protein antigens usually have multiple epitopes, thus, there may be a plurality of antibodies binding to one antigen. However, not all antibodies that bind to one antigen could act as a chaperone. Experiments show that some screened anti-human creatine kinase single chain antibodies (scFV) could assist in the folding and stabilizing of the enzyme, while others could not. We built the model of the single chain antibody (scFv-A4) that increased the stability of human creatine kinase (HCK) by the homology modeling method. Epitopes of human creatine kinase were predicted by computer and then the binding of scFv-A4 and HCK was modeled with computer. The calculation results were further combined with the peptide array membrane experiment results to obtain reliable models for the scFv-A4-HCK complex. Based on the above study we gave an explanation about how scFv-A4 could act as a macromolecular chaperone assisting the folding of HCK. This study provides an approach for predicting antigen-antibody binding mode and also a useful theoretical guidance for the study of antibodies' chaperone-like function.",2013 Apr 24,"['Feng, Jianyu', 'Guo, Hong', 'Li, Sen', 'Lu, Tun']",PLoS One,,,True
9a98026855729dd7aa175ca9ed534a73c7fd9a84,PMC,HCV-Induced miR-21 Contributes to Evasion of Host Immune System by Targeting MyD88 and IRAK1,http://dx.doi.org/10.1371/journal.ppat.1003248,PMC3635988,23633945,CC BY,"Upon recognition of viral components by pattern recognition receptors, such as the toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like helicases, cells are activated to produce type I interferon (IFN) and proinflammatory cytokines. These pathways are tightly regulated by the host to prevent an inappropriate cellular response, but viruses can modulate these pathways to proliferate and spread. In this study, we revealed a novel mechanism in which hepatitis C virus (HCV) evades the immune surveillance system to proliferate by activating microRNA-21 (miR-21). We demonstrated that HCV infection upregulates miR-21, which in turn suppresses HCV-triggered type I IFN production, thus promoting HCV replication. Furthermore, we demonstrated that miR-21 targets two important factors in the TLR signaling pathway, myeloid differentiation factor 88 (MyD88) and interleukin-1 receptor-associated kinase 1 (IRAK1), which are involved in HCV-induced type I IFN production. HCV-mediated activation of miR-21 expression requires viral proteins and several signaling components. Moreover, we identified a transcription factor, activating protein-1 (AP-1), which is partly responsible for miR-21 induction in response to HCV infection through PKCε/JNK/c-Jun and PKCα/ERK/c-Fos cascades. Taken together, our results indicate that miR-21 is upregulated during HCV infection and negatively regulates IFN-α signaling through MyD88 and IRAK1 and may be a potential therapeutic target for antiviral intervention.",2013 Apr 25,"['Chen, Yanni', 'Chen, Junbo', 'Wang, Hui', 'Shi, Jingjing', 'Wu, Kailang', 'Liu, Shi', 'Liu, Yingle', 'Wu, Jianguo']",PLoS Pathog,,,True
985bcaae91f49b39ffb29301edef221c46c66034,PMC,Systems Analysis of a RIG-I Agonist Inducing Broad Spectrum Inhibition of Virus Infectivity,http://dx.doi.org/10.1371/journal.ppat.1003298,PMC3635991,23633948,CC BY,"The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic RIG-I and viral RNA structures that contain short hairpin dsRNA and 5′ triphosphate (5′ppp) terminal structure. In the present study, an RNA agonist of RIG-I was synthesized in vitro and shown to stimulate RIG-I-dependent antiviral responses at concentrations in the picomolar range. In human lung epithelial A549 cells, 5′pppRNA specifically stimulated multiple parameters of the innate antiviral response, including IRF3, IRF7 and STAT1 activation, and induction of inflammatory and interferon stimulated genes - hallmarks of a fully functional antiviral response. Evaluation of the magnitude and duration of gene expression by transcriptional profiling identified a robust, sustained and diversified antiviral and inflammatory response characterized by enhanced pathogen recognition and interferon (IFN) signaling. Bioinformatics analysis further identified a transcriptional signature uniquely induced by 5′pppRNA, and not by IFNα-2b, that included a constellation of IRF7 and NF-kB target genes capable of mobilizing multiple arms of the innate and adaptive immune response. Treatment of primary PBMCs or lung epithelial A549 cells with 5′pppRNA provided significant protection against a spectrum of RNA and DNA viruses. In C57Bl/6 mice, intravenous administration of 5′pppRNA protected animals from a lethal challenge with H1N1 Influenza, reduced virus titers in mouse lungs and protected animals from virus-induced pneumonia. Strikingly, the RIG-I-specific transcriptional response afforded partial protection from influenza challenge, even in the absence of type I interferon signaling. This systems approach provides transcriptional, biochemical, and in vivo analysis of the antiviral efficacy of 5′pppRNA and highlights the therapeutic potential associated with the use of RIG-I agonists as broad spectrum antiviral agents.",2013 Apr 25,"['Goulet, Marie-Line', 'Olagnier, David', 'Xu, Zhengyun', 'Paz, Suzanne', 'Belgnaoui, S. Mehdi', 'Lafferty, Erin I.', 'Janelle, Valérie', 'Arguello, Meztli', 'Paquet, Marilene', 'Ghneim, Khader', 'Richards, Stephanie', 'Smith, Andrew', 'Wilkinson, Peter', 'Cameron, Mark', 'Kalinke, Ulrich', 'Qureshi, Salman', 'Lamarre, Alain', 'Haddad, Elias K.', 'Sekaly, Rafick Pierre', 'Peri, Suraj', 'Balachandran, Siddharth', 'Lin, Rongtuan', 'Hiscott, John']",PLoS Pathog,,,True
bdbfaa82df2210193903b96916ffe6fed13694b4,PMC,Inactivation of an enterovirus by airborne disinfectants,http://dx.doi.org/10.1186/1471-2334-13-177,PMC3636024,23587047,CC BY,"BACKGROUND: The activity of airborne disinfectants on bacteria, fungi and spores has been reported. However, the issue of the virucidal effect of disinfectants spread by fogging has not been studied thoroughly. METHODS: A procedure has been developed to determine the virucidal activity of peracetic acid-based airborne disinfectants on a resistant non-enveloped virus poliovirus type 1. This virus was laid on a stainless carrier. The products were spread into the room by hot fogging at 55°C for 30 minutes at a concentration of 7.5 mL.m(-3). Poliovirus inoculum, supplemented with 5%, heat inactivated non fat dry organic milk, were applied into the middle of the stainless steel disc and were dried under the air flow of a class II biological safety cabinet at room temperature. The Viral preparations were recovered by using flocked swabs and were titered on Vero cells using the classical Spearman-Kärber CPE reading method, the results were expressed as TCID50.ml(-1). RESULTS: The infectious titer of dried poliovirus inocula was kept at 10(5) TCID(50).mL(-1) up to 150 minutes at room temperature. Dried inocula exposed to airborne peracetic acid containing disinfectants were recovered at 60 and 120 minutes post-exposition and suspended in culture medium again. The cytotoxicity of disinfectant containing medium was eliminated through gel filtration columns. A 4 log reduction of infectious titer of dried poliovirus inocula exposed to peracetic-based airborne disinfectant was obtained. CONCLUSION: This study demonstrates that the virucidal activity of airborne disinfectants can be tested on dried poliovirus.",2013 Apr 15,"['Thevenin, Thomas', 'Lobert, Pierre-Emmanuel', 'Hober, Didier']",BMC Infect Dis,,,True
3eb3c6212432888ecf0f2d3d2dc4a2fb6b4f17c0,PMC,CGAP: a new comprehensive platform for the comparative analysis of chloroplast genomes,http://dx.doi.org/10.1186/1471-2105-14-95,PMC3636126,23496817,CC BY,"BACKGROUND: Chloroplast is an essential organelle in plants which contains independent genome. Chloroplast genomes have been widely used for plant phylogenetic inference recently. The number of complete chloroplast genomes increases rapidly with the development of various genome sequencing projects. However, no comprehensive platform or tool has been developed for the comparative and phylogenetic analysis of chloroplast genomes. Thus, we constructed a comprehensive platform for the comparative and phylogenetic analysis of complete chloroplast genomes which was named as chloroplast genome analysis platform (CGAP). RESULTS: CGAP is an interactive web-based platform which was designed for the comparative analysis of complete chloroplast genomes. CGAP integrated genome collection, visualization, content comparison, phylogeny analysis and annotation functions together. CGAP implemented four web servers including creating complete and regional genome maps of high quality, comparing genome features, constructing phylogenetic trees using complete genome sequences, and annotating draft chloroplast genomes submitted by users. CONCLUSIONS: Both CGAP and source code are available at http://www.herbbol.org:8000/chloroplast. CGAP will facilitate the collection, visualization, comparison and annotation of complete chloroplast genomes. Users can customize the comparative and phylogenetic analysis using their own unpublished chloroplast genomes.",2013 Mar 14,"['Cheng, Jinkui', 'Zeng, Xu', 'Ren, Guomin', 'Liu, Zhihua']",BMC Bioinformatics,,,True
72e1bab73b7f05d68543660981e0c8cef749c045,PMC,"Accuracy of IgM antibody testing, FQ-PCR and culture in laboratory diagnosis of acute infection by Mycoplasma pneumoniae in adults and adolescents with community-acquired pneumonia",http://dx.doi.org/10.1186/1471-2334-13-172,PMC3637260,23578215,CC BY,"BACKGROUND: Diagnosis of community-acquired pneumonia (CAP) caused by Mycoplasma pneumoniae in adults and adolescents is hampered by a lack of rapid and standardized tests for detection. METHODS: CAP patients from 12 teaching hospitals were prospectively and consecutively recruited. Basic and clinical information, throat swabs and paired sera were collected. Mycoplasma pneumoniae was detected by IgG and IgM antibody tests, fluorescence quantitative polymerase chain reaction (FQ-PCR) and culture. A comparative study of the diagnostic values of three methods, including sensitivity, specificity, positive and negative predictive values and positive likelihood ratio (PLR) was conducted. A fourfold or greater increase of IgG antibody titers of paired sera was set as the diagnostic “gold standard”. RESULTS: One hundred and twenty-five CAP patients (52.8% males, median age 47 years, range 14–85) were enrolled. Twenty-seven (21.6%) patients were diagnosed with acute Mycoplasma pneumoniae infections by the “gold standard”. Specificity values of all three methods were around 90%. An increasing trend of sensitivity, positive predictive value and PLR was found, with the lowest in IgM testing (7.4%, 28.6% and 1.45), intermediate in FQ-PCR (40.7%, 50% and 3.63), and highest in culture (55.6%, 75% and 10.9). CONCLUSIONS: In the defined group of patients, there was a good agreement between positive rate of MP cultivation of throat swabs and acute M. pneumoniae infection (PLR of 10.9). Since the sensitivity is low in all of the evaluated methods, the logical approach would be to incorporate PCR, culture and serological tests for optimum diagnosis of acute Mycoplasma pneumoniae infections in adults and adolescents.",2013 Apr 11,"['Qu, Jiuxin', 'Gu, Li', 'Wu, Jiang', 'Dong, Jianping', 'Pu, Zenghui', 'Gao, Yan', 'Hu, Ming', 'Zhang, Yongxiang', 'Gao, Feng', 'Cao, Bin', 'Wang, Chen']",BMC Infect Dis,,,True
40c1f536d2ba1ea36ff1f17881df3f1073e76586,PMC,Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events,http://dx.doi.org/10.1186/1479-5876-11-75,PMC3637501,23521917,CC BY,"BACKGROUND: Treatment with ipilimumab, a fully human anti-CTLA-4 antibody approved for the treatment of advanced melanoma, is associated with some immune-related adverse events (irAEs) such as colitis (gastrointestinal irAE, or GI irAE) and skin rash, which are managed by treatment guidelines. Nevertheless, predictive biomarkers that can help identify patients more likely to develop these irAEs could enhance the management of these toxicities. METHODS: To identify candidate predictive biomarkers associated with GI irAEs, gene expression profiling was performed on whole blood samples from 162 advanced melanoma patients at baseline, 3 and 11 weeks after the start of ipilimumab treatment in two phase II clinical trials (CA184004 and CA184007). Overall, 49 patients developed Grade 2 or higher (grade 2+) GI irAEs during the course of treatment. A repeated measures analysis of variance (ANOVA) was used to evaluate the differences in mean expression levels between the GI irAE and No-GI irAE groups of patients at the three time points. RESULTS: In baseline samples, 27 probe sets showed differential mean expression (≥ 1.5 fold, P ≤ 0.05) between the GI irAE and No-GI irAE groups. Most of these probe sets belonged to three functional categories: immune system, cell cycle, and intracellular trafficking. Changes in gene expression over time were also characterized. In the GI irAE group, 58 and 247 probe sets had a ≥ 1.5 fold change in expression from baseline to 3 and 11 weeks after first ipilimumab dose, respectively. In particular, on-treatment expression increases of CD177 and CEACAM1, two neutrophil-activation markers, were closely associated with GI irAEs, suggesting a possible role of neutrophils in ipilimumab-associated GI irAEs. In addition, the expression of several immunoglobulin genes increased over time, with greater increases in patients with grade 2+ GI irAEs. CONCLUSIONS: Gene expression profiling of peripheral blood, sampled before or early in the course of treatment with ipilimumab, resulted in the identification of a set of potential biomarkers that were associated with occurrence of GI irAEs. However, because of the low sensitivity of these biomarkers, they cannot be used alone to predict which patients will develop GI irAEs. Further investigation of these biomarkers in a larger patient cohort is warranted.",2013 Mar 22,"['Shahabi, Vafa', 'Berman, David', 'Chasalow, Scott D', 'Wang, Lisu', 'Tsuchihashi, Zenta', 'Hu, Beihong', 'Panting, Lisa', 'Jure-Kunkel, Maria', 'Ji, Rui-Ru']",J Transl Med,,,True
6fe01cb9f2b36418bd0f5a17bc665e2e02fd2460,PMC,ACE2-Ang-(1-7)-Mas Axis in Brain: A Potential Target for Prevention and Treatment of Ischemic Stroke,http://dx.doi.org/10.2174/1570159X11311020007,PMC3637674,23997755,CC BY,"The renin-angiotensin system (RAS) in brain is a crucial regulator for physiological homeostasis and diseases of cerebrovascular system, such as ischemic stroke. Overactivation of brain Angiotensin-converting enzyme (ACE) - Angiotensin II (Ang II) - Angiotensin II type 1 receptor (AT(1)R) axis was found to be involved in the progress of hypertension, atherosclerosis and thrombogenesis, which increased the susceptibility to ischemic stroke. Besides, brain Ang II levels have been revealed to be increased in ischemic tissues after stroke, and contribute to neural damage through elevating oxidative stress levels and inducing inflammatory response in the ischemic hemisphere via AT(1)R. In recent years, new components of RAS have been discovered, including ACE2, Angiotensin-(1–7) [Ang-(1-7)] and Mas, which constitute ACE2-Ang-(1-7)-Mas axis. ACE2 converts Ang II to Ang-(1-7), and Ang-(1-7) binds with its receptor Mas, exerting benefical effects in cerebrovascular disease. Through interacting with nitric oxide and bradykinin, Ang-(1-7) could attenuate the development of hypertension and the pathologic progress of atherosclerosis. Besides, its antithrombotic activity also prevents thrombogenic events, which may contribute to reduce the risk of ischemic stroke. In addition, after ischemia insult, ACE2-Ang-(1-7)-Mas has been shown to reduce the cerebral infarct size and improve neurological deficits through its antioxidative and anti-inflammatory effects. Taken together, activation of the ACE2-Ang-(1-7)-Mas axis may become a novel therapeutic target in prevention and treatment of ischemia stroke, which deserves further investigations.",2013 Mar,"['Jiang, Teng', 'Gao, Li', 'Lu, Jie', 'Zhang, Ying-Dong']",Curr Neuropharmacol,,,True
9e951559a8cbef877c02296db2e3c2f0ccc8ddec,PMC,Structural Complexity of DNA Sequence,http://dx.doi.org/10.1155/2013/628036,PMC3638703,23662161,CC BY,"In modern bioinformatics, finding an efficient way to allocate sequence fragments with biological functions is an important issue. This paper presents a structural approach based on context-free grammars extracted from original DNA or protein sequences. This approach is radically different from all those statistical methods. Furthermore, this approach is compared with a topological entropy-based method for consistency and difference of the complexity results.",2013 Apr 4,"['Liou, Cheng-Yuan', 'Tseng, Shen-Han', 'Cheng, Wei-Chen', 'Tsai, Huai-Ying']",Comput Math Methods Med,,,True
6a0c165fd5c40909228209e01112875b6d968dea,PMC,"Redescription of Hepatozoon felis (Apicomplexa: Hepatozoidae) based on phylogenetic analysis, tissue and blood form morphology, and possible transplacental transmission",http://dx.doi.org/10.1186/1756-3305-6-102,PMC3639113,23587213,CC BY,"BACKGROUND: A Hepatozoon parasite was initially reported from a cat in India in 1908 and named Leucocytozoon felis domestici. Although domestic feline hepatozoonosis has since been recorded from Europe, Africa, Asia and America, its description, classification and pathogenesis have remained vague and the distinction between different species of Hepatozoon infecting domestic and wild carnivores has been unclear. The aim of this study was to carry out a survey on domestic feline hepatozoonosis and characterize it morphologically and genetically. METHODS: Hepatozoon sp. DNA was amplified by PCR from the blood of 55 of 152 (36%) surveyed cats in Israel and from all blood samples of an additional 19 cats detected as parasitemic by microscopy during routine hematologic examinations. Hepatozoon sp. forms were also characterized from tissues of naturally infected cats. RESULTS: DNA sequencing determined that all cats were infected with Hepatozoon felis except for two infected by Hepatozoon canis. A significant association (p = 0.00001) was found between outdoor access and H. felis infection. H. felis meronts containing merozoites were characterized morphologically from skeletal muscles, myocardium and lungs of H. felis PCR-positive cat tissues and development from early to mature meront was described. Distinctly-shaped gamonts were observed and measured from the blood of these H. felis infected cats. Two fetuses from H. felis PCR-positive queens were positive by PCR from fetal tissue including the lung and amniotic fluid, suggesting possible transplacental transmission. Genetic analysis indicated that H. felis DNA sequences from Israeli cats clustered together with the H. felis Spain 1 and Spain 2 sequences. These cat H. felis sequences clustered separately from the feline H. canis sequences, which grouped with Israeli and foreign dog H. canis sequences. H. felis clustered distinctly from Hepatozoon spp. of other mammals. Feline hepatozoonosis caused by H. felis is mostly sub-clinical as a high proportion of the population is infected with no apparent overt clinical manifestations. CONCLUSIONS: This study aimed to integrate new histopathologic, hematologic, clinical, epidemiological and genetic findings on feline hepatozoonosis and promote the understanding of this infection. The results indicate that feline infection is primarily caused by a morphologically and genetically distinct species, H. felis, which has predilection to infecting muscular tissues, and is highly prevalent in the cat population studied. The lack of previous comprehensively integrated data merits the redescription of this parasite elucidating its parasitological characteristics.",2013 Apr 15,"['Baneth, Gad', 'Sheiner, Alina', 'Eyal, Osnat', 'Hahn, Shelley', 'Beaufils, Jean-Pierre', 'Anug, Yigal', 'Talmi-Frank, Dalit']",Parasit Vectors,,,True
ec2ecade86e6e7660bd8fc929ab0c602cdf16568,PMC,Identification of Residues of SARS-CoV nsp1 That Differentially Affect Inhibition of Gene Expression and Antiviral Signaling,http://dx.doi.org/10.1371/journal.pone.0062416,PMC3639174,23658627,CC BY,"An epidemic of Severe Acute Respiratory Syndrome (SARS) led to the identification of an associated coronavirus, SARS-CoV. This virus evades the host innate immune response in part through the expression of its non-structural protein (nsp) 1, which inhibits both host gene expression and virus- and interferon (IFN)-dependent signaling. Thus, nsp1 is a promising target for drugs, as inhibition of nsp1 would make SARS-CoV more susceptible to the host antiviral defenses. To gain a better understanding of nsp1 mode of action, we generated and analyzed 38 mutants of the SARS-CoV nsp1, targeting 62 solvent exposed residues out of the 180 amino acid protein. From this work, we identified six classes of mutants that abolished, attenuated or increased nsp1 inhibition of host gene expression and/or antiviral signaling. Each class of mutants clustered on SARS-CoV nsp1 surface and suggested nsp1 interacts with distinct host factors to exert its inhibitory activities. Identification of the nsp1 residues critical for its activities and the pathways involved in these activities should help in the design of drugs targeting nsp1. Significantly, several point mutants increased the inhibitory activity of nsp1, suggesting that coronaviruses could evolve a greater ability to evade the host response through mutations of such residues.",2013 Apr 29,"['Jauregui, Andrew R.', 'Savalia, Dhruti', 'Lowry, Virginia K.', 'Farrell, Cara M.', 'Wathelet, Marc G.']",PLoS One,,,True
90a7c8a2e1be47616b2f04bd011c148fcbc8adba,PMC,Regulation of Programmed Ribosomal Frameshifting by Co-Translational Refolding RNA Hairpins,http://dx.doi.org/10.1371/journal.pone.0062283,PMC3639245,23638024,CC BY,"RNA structures are unwound for decoding. In the process, they can pause the elongating ribosome for regulation. An example is the stimulation of -1 programmed ribosomal frameshifting, leading to 3′ direction slippage of the reading-frame during elongation, by specific pseudoknot stimulators downstream of the frameshifting site. By investigating a recently identified regulatory element upstream of the SARS coronavirus (SARS-CoV) −1 frameshifting site, it is shown that a minimal functional element with hairpin forming potential is sufficient to down-regulate−1 frameshifting activity. Mutagenesis to disrupt or restore base pairs in the potential hairpin stem reveals that base-pair formation is required for−1 frameshifting attenuation in vitro and in 293T cells. The attenuation efficiency of a hairpin is determined by its stability and proximity to the frameshifting site; however, it is insensitive to E site sequence variation. Additionally, using a dual luciferase assay, it can be shown that a hairpin stimulated +1 frameshifting when placed upstream of a +1 shifty site in yeast. The investigations indicate that the hairpin is indeed a cis-acting programmed reading-frame switch modulator. This result provides insight into mechanisms governing−1 frameshifting stimulation and attenuation. Since the upstream hairpin is unwound (by a marching ribosome) before the downstream stimulator, this study’s findings suggest a new mode of translational regulation that is mediated by the reformed stem of a ribosomal unwound RNA hairpin during elongation.",2013 Apr 29,"['Cho, Che-Pei', 'Lin, Szu-Chieh', 'Chou, Ming-Yuan', 'Hsu, Hsiu-Ting', 'Chang, Kung-Yao']",PLoS One,,,True
fa07cb83c9ec268f4be524c374659bc3584fca6f,PMC,The tree shrew provides a useful alternative model for the study of influenza H1N1 virus,http://dx.doi.org/10.1186/1743-422X-10-111,PMC3639867,23575279,CC BY,"BACKGROUND: The influenza pandemics have resulted in significant morbidity and mortality worldwide. Animal models are useful in the study of influenza virus pathogenesis. Because of various limitations in current laboratory animal models, it is essential to develop new alternative animal models for influenza virus research aimed at understanding the viral and host factors that contribute to virus infection in human. METHOD: We investigated the replicative efficiency of influenza H1N1 virus (classic strain (Influenza A/PR/8/34), seasonal influenza isolate (A/Guangzhou/GIRD/02/09) and swine-origin human influenza virus (A/Guangzhou/GIRD/07/09)) at Day1,2,4,6 and 9 p.i. using TCID(50) and qPCR assay in tree shrew model. Body temperature was monitored in the morning and evening for 3 days before infection and for 14 days. Seroconversion was detected by determining the neutralizing antibody titers against the challenge viruses in the pre- and exposure serum samples collected before infection and at 14 days p.i., respectively. Lungs and tracheas of tree shews were collected at day 14 post p.i. for histopathological analysis. Lectinhistochemistry analysis was conducted to identify the distribution of SAα2,3 Gal and SAα2,6 Gal receptors in the lung and trachea. RESULTS: The infected tree shrew displayed mild or moderate systemic and respiratory symptoms and pathological changes in respiratory tracts. The human H1N1 influenza virus may replicate in the upper respiratory tract of tree shrews. Analysis of the receptors distribution in the respiratory tract of tree shrews by lectinhistochemistry showed that sialic acid (SA)α2,6-Gal receptors were widely distributed in the trachea and nasal mucosa, whereas (SA)α2,3-Gal receptor was the main receptor in the lung tissue. CONCLUSIONS: Based on these findings, tree shrew seemed to mimic well influenza virus infection in humans. We propose that tree shrews could be a useful alternative mammalian model to study pathogenesis of influenza H1N1 virus.",2013 Apr 10,"['Yang, Zi-feng', 'Zhao, Jin', 'Zhu, Yu-tong', 'Wang, Yu-tao', 'Liu, Rong', 'Zhao, Sui-shan', 'Li, Run-feng', 'Yang, Chun-guang', 'Li, Ji-qiang', 'Zhong, Nan-shan']",Virol J,,,True
a69d1ee507dac9ef068764a5f6cec19be2fbc4a1,PMC,Baicalein Reduces Airway Injury in Allergen and IL-13 Induced Airway Inflammation,http://dx.doi.org/10.1371/journal.pone.0062916,PMC3639905,23646158,CC BY,"BACKGROUND: Baicalein, a bioflavone present in the dry roots of Scutellaria baicalensis Georgi, is known to reduce eotaxin production in human fibroblasts. However, there are no reports of its anti-asthma activity or its effect on airway injury. METHODOLOGY/PRINCIPAL FINDINGS: In a standard experimental asthma model, male Balb/c mice that were sensitized with ovalbumin (OVA), treated with baicalein (10 mg/kg, ip) or a vehicle control, either during (preventive use) or after OVA challenge (therapeutic use). In an alternate model, baicalein was administered to male Balb/c mice which were given either IL-4 or IL-13 intranasally. Features of asthma were determined by estimating airway hyperresponsiveness (AHR), histopathological changes and biochemical assays of key inflammatory molecules. Airway injury was determined with apoptotic assays, transmission electron microscopy and assessing key mitochondrial functions. Baicalein treatment reduced AHR and inflammation in both experimental models. TGF-β(1), sub-epithelial fibrosis and goblet cell metaplasia, were also reduced. Furthermore, baicalein treatment significantly reduced 12/15-LOX activity, features of mitochondrial dysfunctions, and apoptosis of bronchial epithelia. CONCLUSION/SIGNIFICANCE: Our findings demonstrate that baicalein can attenuate important features of asthma, possibly through the reduction of airway injury and restoration of mitochondrial function.",2013 Apr 30,"['Mabalirajan, Ulaganathan', 'Ahmad, Tanveer', 'Rehman, Rakhshinda', 'Leishangthem, Geeta Devi', 'Dinda, Amit Kumar', 'Agrawal, Anurag', 'Ghosh, Balaram', 'Sharma, Surendra Kumar']",PLoS One,,,True
5900930fcaa79a701a7a31a05c3fb85232f31fc6,PMC,Rosiglitazone Treatment of Type 2 Diabetic db/db Mice Attenuates Urinary Albumin and Angiotensin Converting Enzyme 2 Excretion,http://dx.doi.org/10.1371/journal.pone.0062833,PMC3639987,23646149,CC BY,"Alterations within the renal renin angiotensin system play a pivotal role in the development and progression of cardiovascular and renal disease. Angiotensin converting enzyme 2 (ACE2) is highly expressed in renal tubules and has been shown to be renoprotective in diabetes. The protease, a disintegrin and metalloprotease (ADAM) 17, is involved in the ectodomain shedding of several transmembrane proteins including ACE2. Renal ACE2 and ADAM17 were significantly increased in db/db mice compared to controls. We investigated the effect of the insulin sensitizer, rosiglitazone, on albuminuria, renal ADAM17 protein expression and ACE2 shedding in db/db diabetic mice. Rosiglitazone treatment of db/db mice normalized hyperglycemia, attenuated renal injury and decreased urinary ACE2 and renal ADAM17 protein expression. Urinary excreted ACE2 is enzymatically active. Western blot analysis of urinary ACE2 demonstrated two prominent immunoreactive bands at approximately 70 & 90 kDa. The predominant immunoreactive band is approximately 20 kDa shorter than the one demonstrated for kidney lysate, indicating possible ectodomain shedding of active renal ACE2 in the urine. Therefore, it is tempting to speculate that renoprotection of rosiglitazone could be partially mediated via downregulation of renal ADAM17 and ACE2 shedding. In addition, there was a positive correlation between blood glucose, urinary albumin, plasma glucagon, and triglyceride levels with urinary ACE2 excretion. In conclusion, urinary ACE2 could be used as a sensitive biomarker of diabetic nephropathy and for monitoring the effectiveness of renoprotective medication.",2013 Apr 30,"['Chodavarapu, Harshita', 'Grobe, Nadja', 'Somineni, Hari K.', 'Salem, Esam S. B.', 'Madhu, Malav', 'Elased, Khalid M.']",PLoS One,,,True
7150b10d52da822055fd899a9df210131bf8104e,PMC,High Human Bocavirus Viral Load Is Associated with Disease Severity in Children under Five Years of Age,http://dx.doi.org/10.1371/journal.pone.0062318,PMC3640090,23638038,CC BY,"Human bocavirus (HBoV) is a parvovirus and detected worldwide in lower respiratory tract infections (LRTIs), but its pathogenic role in respiratory illness is still debatable due to high incidence of co-infection with other respiratory viruses. To determine the prevalence of HBoV infection in patients with LRTI in Shanghai and its correlation with disease severity, we performed a 3-year prospective study of HBoV in healthy controls, outpatients and inpatients under five years of age with X-ray diagnosed LRTIs. Nasopharyngeal aspirates were tested by PCR for common respiratory viruses and by real time PCR for HBoV subtypes 1–4. Nasopharyngeal swabs from healthy controls and serum samples and stools from inpatients were also tested for HBoV1-4 by real time PCR. Viral loads were determined by quantitative real time PCR in all HBoV positive samples. HBoV1 was detected in 7.0% of inpatients, with annual rates of 5.1%, 8.0% and 4.8% in 2010, 2011 and 2012, respectively. Respiratory syncytial virus (RSV) subtype A was the most frequent co-infection detected; HBoV1 and RSVA appeared to co-circulate with similar seasonal variations. High HBoV viral loads (>10(6) copies/ml) were significantly more frequent in inpatients and outpatients than in healthy controls. There was a direct correlation of high viral load with increasing disease severity in patients co-infected with HBoV1 and at least one other respiratory virus. In summary, our data suggest that HBoV1 can cause LRTIs, but symptomatic HBoV infection is only observed in the context of high viral load.",2013 Apr 30,"['Zhao, Baihui', 'Yu, Xuelian', 'Wang, Chuanxian', 'Teng, Zheng', 'Wang, Chun', 'Shen, Jiaren', 'Gao, Ye', 'Zhu, Zhaokui', 'Wang, Jiayu', 'Yuan, Zhengan', 'Wu, Fan', 'Zhang, Xi', 'Ghildyal, Reena']",PLoS One,,,True
979d953fe8641bdfaf6479a9b479923aae95c86b,PMC,Is there a Role for Cyclophilin Inhibitors in the Management of Primary Biliary Cirrhosis?,http://dx.doi.org/10.3390/v5020423,PMC3640509,23348060,CC BY,"Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are poorly understood autoimmune liver diseases. Immunosuppression is used to treat AIH and ursodeoxycholic acid is used to slow the progression of PBC. Nevertheless, a proportion of patients with both disorders progress to liver failure. Following liver transplantation, up to a third of patients with PBC experience recurrent disease. Moreover a syndrome referred to as “de novo AIH” occurs in a proportion of patients regardless of maintenance immunosuppression, who have been transplanted for disorders unrelated to AIH. Of note, the use of cyclosporine A appears to protect against the development of recurrent PBC and de novo AIH even though it is a less potent immunosuppressive compared to tacrolimus. The reason why cyclosporine A is protective has not been determined. However, a virus resembling mouse mammary tumor virus (MMTV) has been characterized in patients with PBC and AIH. Accordingly, we hypothesized that the protective effect of cyclosporine A in liver transplant recipients may be mediated by the antiviral activity of this cyclophilin inhibitor. Treatment of the MMTV producing MM5MT cells with different antivirals and immunosuppressive agents showed that both cyclosporine A and the analogue NIM811 inhibited MMTV production from the producer cells. Herein, we discuss the evidence supporting the role of MMTV-like human betaretrovirus in the development of PBC and de novo AIH and speculate on the possibility that the agent may be associated with disease following transplantation. We also review the mechanisms of how both cyclosporine A and NIM811 may inhibit betaretrovirus production in vitro.",2013 Jan 24,"['Wasilenko, Shawn T.', 'Montano-Loza, Aldo J.', 'Mason, Andrew L.']",Viruses,,,True
0257dffb6a2cc8bdf6d252c400a38419ef256505,PMC,"Genetic Diversity of Spike, 3a, 3b and E Genes of Infectious Bronchitis Viruses and Emergence of New Recombinants in Korea",http://dx.doi.org/10.3390/v5020550,PMC3640513,23435235,CC BY,"The nucleotide sequences of a region including S1, S2, 3a, 3b and E genes of twenty-seven infectious bronchitis virus (IBV) isolates in Korea between 1990–2011 were determined and phylogenetic and computational recombination analyses were conducted. The sizes of coding regions of some genes varied among IBV isolates due to deletion or insertion of nucleotides; the nucleotide similarities of S1, S2, 3a, 3b and E genes among the 27 isolates were 75.9%–100.0%, 85%–100.0%, 64.0%–100.0%, 60.4%–100.0% and 83.1%–100.0%, respectively. According to phylogenetic analysis of S1 gene, the 27 isolates were divided into five genotypes, Mass, Korean-I (K-I), QX-like, KM91-like and New cluster 1. The phylogenetic trees based on the S2, 3a, 3b, E genes and S1-S2-3a-3b-E (S1-E) region nucleotide sequences did not closely follow the clustering based on the S1 sequence. The New cluster 1 prevalent during 2009 and 2010 was not found in 2011 but QX-like viruses became prevalent in 2011. The recombination analysis revealed two new S gene recombinants, 11036 and 11052 which might have been derived from recombinations between the New cluster 1 and QX-like viruses and between the K-I and H120 (vaccine) viruses, respectively. In conclusion, multiple IBV genotypes have co-circulated; QX-like viruses have recurred and new recombinants have emerged in Korea. This has enriched molecular epidemiology information of IBV and is useful for the control of IB in Korea.",2013 Jan 31,"['Mo, Mei-Lan', 'Hong, Seung-Min', 'Kwon, Hyuk-Joon', 'Kim, Il-Hwan', 'Song, Chang-Seon', 'Kim, Jae-Hong']",Viruses,,,True
57161303ee1012d71c8ea6ad076f2033759f897d,PMC,"Genetic Diversity of Spike, 3a, 3b and E Genes of Infectious Bronchitis Viruses and Emergence of New Recombinants in Korea",http://dx.doi.org/10.3390/v5020550,PMC3640513,23435235,CC BY,"The nucleotide sequences of a region including S1, S2, 3a, 3b and E genes of twenty-seven infectious bronchitis virus (IBV) isolates in Korea between 1990–2011 were determined and phylogenetic and computational recombination analyses were conducted. The sizes of coding regions of some genes varied among IBV isolates due to deletion or insertion of nucleotides; the nucleotide similarities of S1, S2, 3a, 3b and E genes among the 27 isolates were 75.9%–100.0%, 85%–100.0%, 64.0%–100.0%, 60.4%–100.0% and 83.1%–100.0%, respectively. According to phylogenetic analysis of S1 gene, the 27 isolates were divided into five genotypes, Mass, Korean-I (K-I), QX-like, KM91-like and New cluster 1. The phylogenetic trees based on the S2, 3a, 3b, E genes and S1-S2-3a-3b-E (S1-E) region nucleotide sequences did not closely follow the clustering based on the S1 sequence. The New cluster 1 prevalent during 2009 and 2010 was not found in 2011 but QX-like viruses became prevalent in 2011. The recombination analysis revealed two new S gene recombinants, 11036 and 11052 which might have been derived from recombinations between the New cluster 1 and QX-like viruses and between the K-I and H120 (vaccine) viruses, respectively. In conclusion, multiple IBV genotypes have co-circulated; QX-like viruses have recurred and new recombinants have emerged in Korea. This has enriched molecular epidemiology information of IBV and is useful for the control of IB in Korea.",2013 Jan 31,"['Mo, Mei-Lan', 'Hong, Seung-Min', 'Kwon, Hyuk-Joon', 'Kim, Il-Hwan', 'Song, Chang-Seon', 'Kim, Jae-Hong']",Viruses,,,False
cb56f2e5caa4992c01aedc47943146ee81cac007,PMC,Intrathecal Humoral Immunity to Encephalitic RNA Viruses,http://dx.doi.org/10.3390/v5020732,PMC3640523,23435240,CC BY,"The nervous system is the target for acute encephalitic viral infections, as well as a reservoir for persisting viruses. Intrathecal antibody (Ab) synthesis is well documented in humans afflicted by infections associated with neurological complications, as well as the demyelinating disease, multiple sclerosis. This review focuses on the origin, recruitment, maintenance, and biological relevance of Ab-secreting cells (ASC) found in the central nervous system (CNS) following experimental neurotropic RNA virus infections. We will summarize evidence for a highly dynamic, evolving humoral response characterized by temporal alterations in B cell subsets, proliferation, and differentiation. Overall local Ab plays a beneficial role via complement-independent control of virus replication, although cross or self-reactive Ab to CNS antigens may contribute to immune-mediated pathogenesis during some infections. Importantly, protective Ab exert anti-viral activity not only by direct neutralization, but also by binding to cell surface-expressed viral glycoproteins. Ab engagement of viral glycoproteins blocks budding and mediates intracellular signaling leading to restored homeostatic and innate functions. The sustained Ab production by local ASC, as well as chemokines and cytokines associated with ASC recruitment and retention, are highlighted as critical components of immune control.",2013 Feb 15,"['Phares, Timothy W.', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.']",Viruses,,,True
142a615ffb970d12beaa9597bff2b9c49da4bb96,PMC,Risk factors for severe acute lower respiratory infections in children – a systematic review and meta-analysis,http://dx.doi.org/10.3325/cmj.2013.54.110,PMC3641871,23630139,CC BY,"AIM: To identify the risk factors in children under five years of age for severe acute lower respiratory infections (ALRI), which are the leading cause of child mortality. METHODS: We performed a systematic review of published literature available in the public domain. We conducted a quality assessment of all eligible studies according to GRADE criteria and performed a meta-analysis to report the odds ratios for all risk factors identified in these studies. RESULTS: We identified 36 studies that investigated 19 risk factors for severe ALRI. Of these, 7 risk factors were significantly associated with severe ALRI in a consistent manner across studies, with the following meta-analysis estimates of odds ratios (with 95% confidence intervals): low birth weight 3.18 (1.02-9.90), lack of exclusive breastfeeding 2.34 (1.42-3.88), crowding – more than 7 persons per household 1.96 (1.53-2.52), exposure to indoor air pollution 1.57 (1.06-2.31), incomplete immunization 1.83 (1.32-2.52), undernutrition – weight-for-age less than 2 standard deviations 4.47 (2.10-9.49), and HIV infection 4.15 (2.57-9.74). CONCLUSION: This study highlights the role of the above seven risk factors in the development of severe pneumonia in under-five children. In addition, it emphasizes the need for further studies investigating other potential risk factors. Since these risk factors are potentially preventable, health policies targeted at reducing their prevalence provide a basis for decreasing the burden of childhood pneumonia.",2013 Apr,"['Jackson, Stewart', 'Mathews, Kyle H.', 'Pulanić, Dražen', 'Falconer, Rachel', 'Rudan, Igor', 'Campbell, Harry', 'Nair, Harish']",Croat Med J,,,True
6aedd9fc4bea8ecfcbea50546a50431a6ebfce67,PMC,Risk factors for severe acute lower respiratory infections in children – a systematic review and meta-analysis,http://dx.doi.org/10.3325/cmj.2013.54.110,PMC3641871,23630139,CC BY,"AIM: To identify the risk factors in children under five years of age for severe acute lower respiratory infections (ALRI), which are the leading cause of child mortality. METHODS: We performed a systematic review of published literature available in the public domain. We conducted a quality assessment of all eligible studies according to GRADE criteria and performed a meta-analysis to report the odds ratios for all risk factors identified in these studies. RESULTS: We identified 36 studies that investigated 19 risk factors for severe ALRI. Of these, 7 risk factors were significantly associated with severe ALRI in a consistent manner across studies, with the following meta-analysis estimates of odds ratios (with 95% confidence intervals): low birth weight 3.18 (1.02-9.90), lack of exclusive breastfeeding 2.34 (1.42-3.88), crowding – more than 7 persons per household 1.96 (1.53-2.52), exposure to indoor air pollution 1.57 (1.06-2.31), incomplete immunization 1.83 (1.32-2.52), undernutrition – weight-for-age less than 2 standard deviations 4.47 (2.10-9.49), and HIV infection 4.15 (2.57-9.74). CONCLUSION: This study highlights the role of the above seven risk factors in the development of severe pneumonia in under-five children. In addition, it emphasizes the need for further studies investigating other potential risk factors. Since these risk factors are potentially preventable, health policies targeted at reducing their prevalence provide a basis for decreasing the burden of childhood pneumonia.",2013 Apr,"['Jackson, Stewart', 'Mathews, Kyle H.', 'Pulanić, Dražen', 'Falconer, Rachel', 'Rudan, Igor', 'Campbell, Harry', 'Nair, Harish']",Croat Med J,,,False
f3adb474ad03cc606ada08752245a6cc86aaaaa1,PMC,Risk factors for severe acute lower respiratory infections in children – a systematic review and meta-analysis,http://dx.doi.org/10.3325/cmj.2013.54.110,PMC3641871,23630139,CC BY,"AIM: To identify the risk factors in children under five years of age for severe acute lower respiratory infections (ALRI), which are the leading cause of child mortality. METHODS: We performed a systematic review of published literature available in the public domain. We conducted a quality assessment of all eligible studies according to GRADE criteria and performed a meta-analysis to report the odds ratios for all risk factors identified in these studies. RESULTS: We identified 36 studies that investigated 19 risk factors for severe ALRI. Of these, 7 risk factors were significantly associated with severe ALRI in a consistent manner across studies, with the following meta-analysis estimates of odds ratios (with 95% confidence intervals): low birth weight 3.18 (1.02-9.90), lack of exclusive breastfeeding 2.34 (1.42-3.88), crowding – more than 7 persons per household 1.96 (1.53-2.52), exposure to indoor air pollution 1.57 (1.06-2.31), incomplete immunization 1.83 (1.32-2.52), undernutrition – weight-for-age less than 2 standard deviations 4.47 (2.10-9.49), and HIV infection 4.15 (2.57-9.74). CONCLUSION: This study highlights the role of the above seven risk factors in the development of severe pneumonia in under-five children. In addition, it emphasizes the need for further studies investigating other potential risk factors. Since these risk factors are potentially preventable, health policies targeted at reducing their prevalence provide a basis for decreasing the burden of childhood pneumonia.",2013 Apr,"['Jackson, Stewart', 'Mathews, Kyle H.', 'Pulanić, Dražen', 'Falconer, Rachel', 'Rudan, Igor', 'Campbell, Harry', 'Nair, Harish']",Croat Med J,,,False
f0a8aaaee772b9a00fcddc3d82448ec5b71c2d03,PMC,Risk factors for severe acute lower respiratory infections in children – a systematic review and meta-analysis,http://dx.doi.org/10.3325/cmj.2013.54.110,PMC3641871,23630139,CC BY,"AIM: To identify the risk factors in children under five years of age for severe acute lower respiratory infections (ALRI), which are the leading cause of child mortality. METHODS: We performed a systematic review of published literature available in the public domain. We conducted a quality assessment of all eligible studies according to GRADE criteria and performed a meta-analysis to report the odds ratios for all risk factors identified in these studies. RESULTS: We identified 36 studies that investigated 19 risk factors for severe ALRI. Of these, 7 risk factors were significantly associated with severe ALRI in a consistent manner across studies, with the following meta-analysis estimates of odds ratios (with 95% confidence intervals): low birth weight 3.18 (1.02-9.90), lack of exclusive breastfeeding 2.34 (1.42-3.88), crowding – more than 7 persons per household 1.96 (1.53-2.52), exposure to indoor air pollution 1.57 (1.06-2.31), incomplete immunization 1.83 (1.32-2.52), undernutrition – weight-for-age less than 2 standard deviations 4.47 (2.10-9.49), and HIV infection 4.15 (2.57-9.74). CONCLUSION: This study highlights the role of the above seven risk factors in the development of severe pneumonia in under-five children. In addition, it emphasizes the need for further studies investigating other potential risk factors. Since these risk factors are potentially preventable, health policies targeted at reducing their prevalence provide a basis for decreasing the burden of childhood pneumonia.",2013 Apr,"['Jackson, Stewart', 'Mathews, Kyle H.', 'Pulanić, Dražen', 'Falconer, Rachel', 'Rudan, Igor', 'Campbell, Harry', 'Nair, Harish']",Croat Med J,,,False
bb155121c9a40b8b3dbb5fa669e2686d68bb31df,PMC,Risk factors for severe acute lower respiratory infections in children – a systematic review and meta-analysis,http://dx.doi.org/10.3325/cmj.2013.54.110,PMC3641871,23630139,CC BY,"AIM: To identify the risk factors in children under five years of age for severe acute lower respiratory infections (ALRI), which are the leading cause of child mortality. METHODS: We performed a systematic review of published literature available in the public domain. We conducted a quality assessment of all eligible studies according to GRADE criteria and performed a meta-analysis to report the odds ratios for all risk factors identified in these studies. RESULTS: We identified 36 studies that investigated 19 risk factors for severe ALRI. Of these, 7 risk factors were significantly associated with severe ALRI in a consistent manner across studies, with the following meta-analysis estimates of odds ratios (with 95% confidence intervals): low birth weight 3.18 (1.02-9.90), lack of exclusive breastfeeding 2.34 (1.42-3.88), crowding – more than 7 persons per household 1.96 (1.53-2.52), exposure to indoor air pollution 1.57 (1.06-2.31), incomplete immunization 1.83 (1.32-2.52), undernutrition – weight-for-age less than 2 standard deviations 4.47 (2.10-9.49), and HIV infection 4.15 (2.57-9.74). CONCLUSION: This study highlights the role of the above seven risk factors in the development of severe pneumonia in under-five children. In addition, it emphasizes the need for further studies investigating other potential risk factors. Since these risk factors are potentially preventable, health policies targeted at reducing their prevalence provide a basis for decreasing the burden of childhood pneumonia.",2013 Apr,"['Jackson, Stewart', 'Mathews, Kyle H.', 'Pulanić, Dražen', 'Falconer, Rachel', 'Rudan, Igor', 'Campbell, Harry', 'Nair, Harish']",Croat Med J,,,False
428d1091cf63872ea81cb3c1632d76c4813748a1,PMC,Viral etiology of hospitalized acute lower respiratory infections in children under 5 years of age – a systematic review and meta-analysis,http://dx.doi.org/10.3325/cmj.2013.54.122,PMC3641872,23630140,CC BY,"AIM: To estimate the proportional contribution of influenza viruses (IV), parainfluenza viruses (PIV), adenoviruses (AV), and coronaviruses (CV) to the burden of severe acute lower respiratory infections (ALRI). METHODS: The review of the literature followed PRISMA guidelines. We included studies of hospitalized children aged 0-4 years with confirmed ALRI published between 1995 and 2011. A total of 51 studies were included in the final review, comprising 56 091 hospitalized ALRI episodes. RESULTS: IV was detected in 3.0% (2.2%-4.0%) of all hospitalized ALRI cases, PIV in 2.7% (1.9%-3.7%), and AV in 5.8% (3.4%-9.1%). CV are technically difficult to culture, and they were detected in 4.8% of all hospitalized ALRI patients in one study. When respiratory syncytial virus (RSV) and less common viruses were included, at least one virus was detected in 50.4% (40.0%-60.7%) of all hospitalized severe ALRI episodes. Moreover, 21.9% (17.7%-26.4%) of these viral ALRI were mixed, including more than one viral pathogen. Among all severe ALRI with confirmed viral etiology, IV accounted for 7.0% (5.5%-8.7%), PIV for 5.8% (4.1%-7.7%), and AV for 8.8% (5.3%-13.0%). CV was found in 10.6% of virus-positive pneumonia patients in one study. CONCLUSIONS: This article provides the most comprehensive analysis of the contribution of four viral causes to severe ALRI to date. Our results can be used in further cost-effectiveness analyses of vaccine development and implementation for a number of respiratory viruses.",2013 Apr,"['Lukšić, Ivana', 'Kearns, Patrick K', 'Scott, Fiona', 'Rudan, Igor', 'Campbell, Harry', 'Nair, Harish']",Croat Med J,,,True
82441199a6d3222ad51244e351b5df2d53aecc0f,PMC,Viral etiology of hospitalized acute lower respiratory infections in children under 5 years of age – a systematic review and meta-analysis,http://dx.doi.org/10.3325/cmj.2013.54.122,PMC3641872,23630140,CC BY,"AIM: To estimate the proportional contribution of influenza viruses (IV), parainfluenza viruses (PIV), adenoviruses (AV), and coronaviruses (CV) to the burden of severe acute lower respiratory infections (ALRI). METHODS: The review of the literature followed PRISMA guidelines. We included studies of hospitalized children aged 0-4 years with confirmed ALRI published between 1995 and 2011. A total of 51 studies were included in the final review, comprising 56 091 hospitalized ALRI episodes. RESULTS: IV was detected in 3.0% (2.2%-4.0%) of all hospitalized ALRI cases, PIV in 2.7% (1.9%-3.7%), and AV in 5.8% (3.4%-9.1%). CV are technically difficult to culture, and they were detected in 4.8% of all hospitalized ALRI patients in one study. When respiratory syncytial virus (RSV) and less common viruses were included, at least one virus was detected in 50.4% (40.0%-60.7%) of all hospitalized severe ALRI episodes. Moreover, 21.9% (17.7%-26.4%) of these viral ALRI were mixed, including more than one viral pathogen. Among all severe ALRI with confirmed viral etiology, IV accounted for 7.0% (5.5%-8.7%), PIV for 5.8% (4.1%-7.7%), and AV for 8.8% (5.3%-13.0%). CV was found in 10.6% of virus-positive pneumonia patients in one study. CONCLUSIONS: This article provides the most comprehensive analysis of the contribution of four viral causes to severe ALRI to date. Our results can be used in further cost-effectiveness analyses of vaccine development and implementation for a number of respiratory viruses.",2013 Apr,"['Lukšić, Ivana', 'Kearns, Patrick K', 'Scott, Fiona', 'Rudan, Igor', 'Campbell, Harry', 'Nair, Harish']",Croat Med J,,,True
1d2268701960bba63d687cc67c9f1864ab05cd00,PMC,Viral etiology of hospitalized acute lower respiratory infections in children under 5 years of age – a systematic review and meta-analysis,http://dx.doi.org/10.3325/cmj.2013.54.122,PMC3641872,23630140,CC BY,"AIM: To estimate the proportional contribution of influenza viruses (IV), parainfluenza viruses (PIV), adenoviruses (AV), and coronaviruses (CV) to the burden of severe acute lower respiratory infections (ALRI). METHODS: The review of the literature followed PRISMA guidelines. We included studies of hospitalized children aged 0-4 years with confirmed ALRI published between 1995 and 2011. A total of 51 studies were included in the final review, comprising 56 091 hospitalized ALRI episodes. RESULTS: IV was detected in 3.0% (2.2%-4.0%) of all hospitalized ALRI cases, PIV in 2.7% (1.9%-3.7%), and AV in 5.8% (3.4%-9.1%). CV are technically difficult to culture, and they were detected in 4.8% of all hospitalized ALRI patients in one study. When respiratory syncytial virus (RSV) and less common viruses were included, at least one virus was detected in 50.4% (40.0%-60.7%) of all hospitalized severe ALRI episodes. Moreover, 21.9% (17.7%-26.4%) of these viral ALRI were mixed, including more than one viral pathogen. Among all severe ALRI with confirmed viral etiology, IV accounted for 7.0% (5.5%-8.7%), PIV for 5.8% (4.1%-7.7%), and AV for 8.8% (5.3%-13.0%). CV was found in 10.6% of virus-positive pneumonia patients in one study. CONCLUSIONS: This article provides the most comprehensive analysis of the contribution of four viral causes to severe ALRI to date. Our results can be used in further cost-effectiveness analyses of vaccine development and implementation for a number of respiratory viruses.",2013 Apr,"['Lukšić, Ivana', 'Kearns, Patrick K', 'Scott, Fiona', 'Rudan, Igor', 'Campbell, Harry', 'Nair, Harish']",Croat Med J,,,False
ac379a37c74e9e9ea13ad9813f46f53dbab62b66,PMC,A geographic analysis of population density thresholds in the influenza pandemic of 1918–19,http://dx.doi.org/10.1186/1476-072X-12-9,PMC3641965,23425498,CC BY,"BACKGROUND: Geographic variables play an important role in the study of epidemics. The role of one such variable, population density, in the spread of influenza is controversial. Prior studies have tested for such a role using arbitrary thresholds for population density above or below which places are hypothesized to have higher or lower mortality. The results of such studies are mixed. The objective of this study is to estimate, rather than assume, a threshold level of population density that separates low-density regions from high-density regions on the basis of population loss during an influenza pandemic. We study the case of the influenza pandemic of 1918–19 in India, where over 15 million people died in the short span of less than one year. METHODS: Using data from six censuses for 199 districts of India (n=1194), the country with the largest number of deaths from the influenza of 1918–19, we use a sample-splitting method embedded within a population growth model that explicitly quantifies population loss from the pandemic to estimate a threshold level of population density that separates low-density districts from high-density districts. RESULTS: The results demonstrate a threshold level of population density of 175 people per square mile. A concurrent finding is that districts on the low side of the threshold experienced rates of population loss (3.72%) that were lower than districts on the high side of the threshold (4.69%). CONCLUSIONS: This paper introduces a useful analytic tool to the health geographic literature. It illustrates an application of the tool to demonstrate that it can be useful for pandemic awareness and preparedness efforts. Specifically, it estimates a level of population density above which policies to socially distance, redistribute or quarantine populations are likely to be more effective than they are for areas with population densities that lie below the threshold.",2013 Feb 20,"['Chandra, Siddharth', 'Kassens-Noor, Eva', 'Kuljanin, Goran', 'Vertalka, Joshua']",Int J Health Geogr,,,True
104905bcc37d4afad386adaeed57fbe4fc73a595,PMC,Inference of R (0) and Transmission Heterogeneity from the Size Distribution of Stuttering Chains,http://dx.doi.org/10.1371/journal.pcbi.1002993,PMC3642075,23658504,CC0,"For many infectious disease processes such as emerging zoonoses and vaccine-preventable diseases, [Image: see text] and infections occur as self-limited stuttering transmission chains. A mechanistic understanding of transmission is essential for characterizing the risk of emerging diseases and monitoring spatio-temporal dynamics. Thus methods for inferring [Image: see text] and the degree of heterogeneity in transmission from stuttering chain data have important applications in disease surveillance and management. Previous researchers have used chain size distributions to infer [Image: see text], but estimation of the degree of individual-level variation in infectiousness (as quantified by the dispersion parameter, [Image: see text]) has typically required contact tracing data. Utilizing branching process theory along with a negative binomial offspring distribution, we demonstrate how maximum likelihood estimation can be applied to chain size data to infer both [Image: see text] and the dispersion parameter that characterizes heterogeneity. While the maximum likelihood value for [Image: see text] is a simple function of the average chain size, the associated confidence intervals are dependent on the inferred degree of transmission heterogeneity. As demonstrated for monkeypox data from the Democratic Republic of Congo, this impacts when a statistically significant change in [Image: see text] is detectable. In addition, by allowing for superspreading events, inference of [Image: see text] shifts the threshold above which a transmission chain should be considered anomalously large for a given value of [Image: see text] (thus reducing the probability of false alarms about pathogen adaptation). Our analysis of monkeypox also clarifies the various ways that imperfect observation can impact inference of transmission parameters, and highlights the need to quantitatively evaluate whether observation is likely to significantly bias results.",2013 May 2,"['Blumberg, Seth', 'Lloyd-Smith, James O.']",PLoS Comput Biol,,,True
80117863dd2a5d88ad1c777af6952bd136811a25,PMC,Inference of R (0) and Transmission Heterogeneity from the Size Distribution of Stuttering Chains,http://dx.doi.org/10.1371/journal.pcbi.1002993,PMC3642075,23658504,CC0,"For many infectious disease processes such as emerging zoonoses and vaccine-preventable diseases, [Image: see text] and infections occur as self-limited stuttering transmission chains. A mechanistic understanding of transmission is essential for characterizing the risk of emerging diseases and monitoring spatio-temporal dynamics. Thus methods for inferring [Image: see text] and the degree of heterogeneity in transmission from stuttering chain data have important applications in disease surveillance and management. Previous researchers have used chain size distributions to infer [Image: see text], but estimation of the degree of individual-level variation in infectiousness (as quantified by the dispersion parameter, [Image: see text]) has typically required contact tracing data. Utilizing branching process theory along with a negative binomial offspring distribution, we demonstrate how maximum likelihood estimation can be applied to chain size data to infer both [Image: see text] and the dispersion parameter that characterizes heterogeneity. While the maximum likelihood value for [Image: see text] is a simple function of the average chain size, the associated confidence intervals are dependent on the inferred degree of transmission heterogeneity. As demonstrated for monkeypox data from the Democratic Republic of Congo, this impacts when a statistically significant change in [Image: see text] is detectable. In addition, by allowing for superspreading events, inference of [Image: see text] shifts the threshold above which a transmission chain should be considered anomalously large for a given value of [Image: see text] (thus reducing the probability of false alarms about pathogen adaptation). Our analysis of monkeypox also clarifies the various ways that imperfect observation can impact inference of transmission parameters, and highlights the need to quantitatively evaluate whether observation is likely to significantly bias results.",2013 May 2,"['Blumberg, Seth', 'Lloyd-Smith, James O.']",PLoS Comput Biol,,,False
7e0a164300efd5ab4d734ae591fcd8b4ef3554f8,PMC,Inference of R (0) and Transmission Heterogeneity from the Size Distribution of Stuttering Chains,http://dx.doi.org/10.1371/journal.pcbi.1002993,PMC3642075,23658504,CC0,"For many infectious disease processes such as emerging zoonoses and vaccine-preventable diseases, [Image: see text] and infections occur as self-limited stuttering transmission chains. A mechanistic understanding of transmission is essential for characterizing the risk of emerging diseases and monitoring spatio-temporal dynamics. Thus methods for inferring [Image: see text] and the degree of heterogeneity in transmission from stuttering chain data have important applications in disease surveillance and management. Previous researchers have used chain size distributions to infer [Image: see text], but estimation of the degree of individual-level variation in infectiousness (as quantified by the dispersion parameter, [Image: see text]) has typically required contact tracing data. Utilizing branching process theory along with a negative binomial offspring distribution, we demonstrate how maximum likelihood estimation can be applied to chain size data to infer both [Image: see text] and the dispersion parameter that characterizes heterogeneity. While the maximum likelihood value for [Image: see text] is a simple function of the average chain size, the associated confidence intervals are dependent on the inferred degree of transmission heterogeneity. As demonstrated for monkeypox data from the Democratic Republic of Congo, this impacts when a statistically significant change in [Image: see text] is detectable. In addition, by allowing for superspreading events, inference of [Image: see text] shifts the threshold above which a transmission chain should be considered anomalously large for a given value of [Image: see text] (thus reducing the probability of false alarms about pathogen adaptation). Our analysis of monkeypox also clarifies the various ways that imperfect observation can impact inference of transmission parameters, and highlights the need to quantitatively evaluate whether observation is likely to significantly bias results.",2013 May 2,"['Blumberg, Seth', 'Lloyd-Smith, James O.']",PLoS Comput Biol,,,False
792417a1bbb50a19ce96e8354aa9f16f2424b850,PMC,High incidence of respiratory viruses in critically ill adult patients with respiratory failure,http://dx.doi.org/10.1186/cc12073,PMC3642395,,CC BY,,2013 Mar 19,"['Sietses, M', 'Faber, TE', 'Bont, L', 'Buter, H', 'Boerma, EC']",Crit Care,,,True
29e75f8938836f57cbdfa2e73f05939ee5f561a1,PMC,A Comparison of the Clinical and Epidemiological Characteristics of Adult Patients with Laboratory-Confirmed Influenza A or B during the 2011–2012 Influenza Season in Korea: A Multi-Center Study,http://dx.doi.org/10.1371/journal.pone.0062685,PMC3643978,23671624,CC BY,"BACKGROUND: During the 2011/2012 winter influenza season in the Republic of Korea, influenza A (H3N2) was the predominant virus in the first peak period of influenza activity during the second half of January 2012. On the other hand, influenza B was the predominant virus in the second peak period of influenza activity during the second half of March 2012. The objectives of this study were to compare the clinical and epidemiological characteristics of patients with laboratory-confirmed influenza A or influenza B. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed data from 2,129 adult patients with influenza-like illnesses who visited the emergency rooms of seven university hospitals in Korea from October 2011 to May 2012. Of 850 patients with laboratory-confirmed influenza, 656 (77.2%) had influenza A (H3N2), and 194 (22.8%) influenza B. Age, and the frequencies of cardiovascular disorders, diabetes, hypertension were significantly higher in patients with influenza A (H3N2) (P<0.05). The frequencies of leukopenia or thrombocytopenia in patients with influenza B at initial presentation were statistically higher than those in patients with influenza A (H3N2) (P<0.05). The rate of hospitalization, and length of hospital stay were statistically higher in patients with influenza A (H3N2) (P<0.05), and of the 79 hospitalized patients, the frequency of diabetes, hypertension, cases having at least one of the comorbid conditions, and the proportion of elderly were significantly higher in patients with influenza A (H3N2) (P<0.05). CONCLUSIONS: The proportion of males to females and elderly population were significantly higher for influenza A (H3N2) patients group compared with influenza B group. Hypertension, diabetes, chronic lung diseases, cardiovascular disorders, and neuromuscular diseases were independently associated with hospitalization due to influenza. Physicians should assess and treat the underlying comorbid conditions as well as influenza viral infections for the appropriate management of patients with influenza.",2013 May 3,"['Wie, Seong-Heon', 'So, Byung Hak', 'Song, Joon Young', 'Cheong, Hee Jin', 'Seo, Yu Bin', 'Choi, Sung Hyuk', 'Noh, Ji Yun', 'Baek, Ji Hyeon', 'Lee, Jin Soo', 'Kim, Hyo Youl', 'Kim, Young Keun', 'Choi, Won Suk', 'Lee, Jacob', 'Jeong, Hye Won', 'Kim, Woo Joo']",PLoS One,,,True
bc7c67f8bf777ec11fcdfdbd36ed0c3fb55f2c72,PMC,Age-specific contacts and travel patterns in the spatial spread of 2009 H1N1 influenza pandemic,http://dx.doi.org/10.1186/1471-2334-13-176,PMC3644502,23587010,CC BY,"BACKGROUND: Confirmed H1N1 cases during late spring and summer 2009 in various countries showed a substantial age shift between importations and local transmission cases, with adults mainly responsible for seeding unaffected regions and children most frequently driving community outbreaks. METHODS: We introduce a multi-host stochastic metapopulation model with two age classes to analytically investigate the role of a heterogeneously mixing population and its associated non-homogeneous travel behaviors on the risk of a major epidemic. We inform the model with demographic data, contact data and travel statistics of Europe and Mexico, and calibrate it to the 2009 H1N1 pandemic early outbreak. We allow for variations of the model parameters to explore the conditions of invasion under different scenarios. RESULTS: We derive the expression for the potential of global invasion of the epidemic that depends on the transmissibility of the pathogen, the transportation network and mobility features, the demographic profile and the mixing pattern. Higher assortativity in the contact pattern greatly increases the probability of spatial containment of the epidemic, this effect being contrasted by an increase in the social activity of adults vs. children. Heterogeneous features of the mobility network characterizing its topology and traffic flows strongly favor the invasion of the pathogen at the spatial level, as also a larger fraction of children traveling. Variations in the demographic profile and mixing habits across countries lead to heterogeneous outbreak situations. Model results are compatible with the H1N1 spatial transmission dynamics observed. CONCLUSIONS: This work illustrates the importance of considering age-dependent mixing profiles and mobility features coupled together to study the conditions for the spatial invasion of an emerging influenza pandemic. Its results allow the immediate assessment of the risk of a major epidemic for a specific scenario upon availability of data, and the evaluation of the potential effectiveness of public health interventions targeting specific age groups, their interactions and mobility behaviors. The approach provides a general modeling framework that can be used for other types of partitions of the host population and applied to different settings.",2013 Apr 15,"['Apolloni, Andrea', 'Poletto, Chiara', 'Colizza, Vittoria']",BMC Infect Dis,,,True
1c3e28d4bd170a986bb5566cb9f9616410f67763,PMC,Age-specific contacts and travel patterns in the spatial spread of 2009 H1N1 influenza pandemic,http://dx.doi.org/10.1186/1471-2334-13-176,PMC3644502,23587010,CC BY,"BACKGROUND: Confirmed H1N1 cases during late spring and summer 2009 in various countries showed a substantial age shift between importations and local transmission cases, with adults mainly responsible for seeding unaffected regions and children most frequently driving community outbreaks. METHODS: We introduce a multi-host stochastic metapopulation model with two age classes to analytically investigate the role of a heterogeneously mixing population and its associated non-homogeneous travel behaviors on the risk of a major epidemic. We inform the model with demographic data, contact data and travel statistics of Europe and Mexico, and calibrate it to the 2009 H1N1 pandemic early outbreak. We allow for variations of the model parameters to explore the conditions of invasion under different scenarios. RESULTS: We derive the expression for the potential of global invasion of the epidemic that depends on the transmissibility of the pathogen, the transportation network and mobility features, the demographic profile and the mixing pattern. Higher assortativity in the contact pattern greatly increases the probability of spatial containment of the epidemic, this effect being contrasted by an increase in the social activity of adults vs. children. Heterogeneous features of the mobility network characterizing its topology and traffic flows strongly favor the invasion of the pathogen at the spatial level, as also a larger fraction of children traveling. Variations in the demographic profile and mixing habits across countries lead to heterogeneous outbreak situations. Model results are compatible with the H1N1 spatial transmission dynamics observed. CONCLUSIONS: This work illustrates the importance of considering age-dependent mixing profiles and mobility features coupled together to study the conditions for the spatial invasion of an emerging influenza pandemic. Its results allow the immediate assessment of the risk of a major epidemic for a specific scenario upon availability of data, and the evaluation of the potential effectiveness of public health interventions targeting specific age groups, their interactions and mobility behaviors. The approach provides a general modeling framework that can be used for other types of partitions of the host population and applied to different settings.",2013 Apr 15,"['Apolloni, Andrea', 'Poletto, Chiara', 'Colizza, Vittoria']",BMC Infect Dis,,,True
137b25ee1545c4b01332709ab1e24dcf935d6f96,PMC,A Role for Protein Phosphatase 2A in Regulating p38 Mitogen Activated Protein Kinase Activation and Tumor Necrosis Factor-Alpha Expression during Influenza Virus Infection,http://dx.doi.org/10.3390/ijms14047327,PMC3645688,23549267,CC BY,"Influenza viruses of avian origin continue to pose pandemic threats to human health. Some of the H5N1 and H9N2 virus subtypes induce markedly elevated cytokine levels when compared with the seasonal H1N1 virus. We previously showed that H5N1/97 hyperinduces tumor necrosis factor (TNF)-alpha through p38 mitogen activated protein kinase (MAPK). However, the detailed mechanisms of p38MAPK activation and TNF-alpha hyperinduction following influenza virus infections are not known. Negative feedback regulations of cytokine expression play important roles in avoiding overwhelming production of proinflammatory cytokines. Here we hypothesize that protein phosphatases are involved in the regulation of cytokine expressions during influenza virus infection. We investigated the roles of protein phosphatases including MAPK phosphatase-1 (MKP-1) and protein phosphatase type 2A (PP2A) in modulating p38MAPK activation and downstream TNF-alpha expressions in primary human monocyte-derived macrophages (PBMac) infected with H9N2/G1 or H1N1 influenza virus. We demonstrate that H9N2/G1 virus activated p38MAPK and hyperinduced TNF-alpha production in PBMac when compared with H1N1 virus. H9N2/G1 induced PP2A activity in PBMac and, with the treatment of a PP2A inhibitor, p38MAPK phosphorylation and TNF-alpha production were further increased in the virus-infected macrophages. However, H9N2/G1 did not induce the expression of PP2A indicating that the activation of PP2A is not mediated by p38MAPK in virus-infected PBMac. On the other hand, PP2A may not be the targets of H9N2/G1 in the upstream of p38MAPK signaling pathways since H1N1 also induced PP2A activation in primary macrophages. Our results may provide new insights into the control of cytokine dysregulation.",2013 Apr 2,"['Law, Anna H. Y.', 'Tam, Alex H. M.', 'Lee, Davy C. W.', 'Lau, Allan S. Y.']",Int J Mol Sci,,,True
67ef4b8a1eaaf14328ad66f28e0f103c608e73d4,PMC,Identifying Early Inflammatory Changes in Monocyte-Derived Macrophages from a Population with IQ-Discrepant Episodic Memory,http://dx.doi.org/10.1371/journal.pone.0063194,PMC3646027,23671673,CC BY,"BACKGROUND: Cells of the innate immune system including monocytes and macrophages are the first line of defence against infections and are critical regulators of the inflammatory response. These cells express toll-like receptors (TLRs), innate immune receptors which govern tailored inflammatory gene expression patterns. Monocytes, which produce pro-inflammatory mediators, are readily recruited to the central nervous system (CNS) in neurodegenerative diseases. METHODS: This study explored the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and peripheral blood mononuclear cells (PBMCs) isolated from healthy elderly adults who we classified as either IQ memory-consistent (high-performing, HP) or IQ memory-discrepant (low-performing, LP). RESULTS: The expression of CD11b, TLR4 and TLR2 was increased in MDMs from the LP group when compared to HP cohort. MDMs from both groups responded robustly to treatment with the TLR4 activator, lipopolysaccharide (LPS), in terms of cytokine production. Significantly, MDMs from the LP group displayed hypersensitivity to LPS exposure. INTERPRETATION: Overall these findings define differential receptor expression and cytokine profiles that occur in MDMs derived from a cohort of IQ memory-discrepant individuals. These changes are indicative of inflammation and may be involved in the prodromal processes leading to the development of neurodegenerative disease.",2013 May 6,"['Downer, Eric J.', 'Jones, Raasay S.', 'McDonald, Claire L.', 'Greco, Eleonora', 'Brennan, Sabina', 'Connor, Thomas J.', 'Robertson, Ian H.', 'Lynch, Marina A.']",PLoS One,,,True
a58e2554025589270e688199f55c97c719fe874d,PMC,Reinvigorating the Role of Science in Democracy,http://dx.doi.org/10.1371/journal.pbio.1001553,PMC3646724,23667322,CC BY,"Private and political interests routinely conspire to sideline and misrepresent science and evidence in the public policy process. The Center for Science and Democracy, a new initiative at the Union of Concerned Scientists, endeavors to change this dynamic to strengthen the role of science in decision making.",2013 May 7,"['Rosenberg, Andrew A.', 'Halpern, Michael', 'Shulman, Seth', 'Wexler, Celia', 'Phartiyal, Pallavi']",PLoS Biol,,,True
5c78286b1684b83d68551054909958005fc2529a,PMC,The Transient Nature of Bunyamwera Orthobunyavirus NSs Protein Expression: Effects of Increased Stability of NSs Protein on Virus Replication,http://dx.doi.org/10.1371/journal.pone.0064137,PMC3648540,23667701,CC BY,"The NSs proteins of bunyaviruses are the viral interferon antagonists, counteracting the host's antiviral response to infection. During high-multiplicity infection of cultured mammalian cells with Bunyamwera orthobunyavirus (BUNV), NSs is rapidly degraded after reaching peak levels of expression at 12hpi. Through the use of inhibitors this was shown to be the result of proteasomal degradation. A recombinant virus (rBUN4KR), in which all four lysine residues in NSs were replaced by arginine residues, expresses an NSs protein (NSs4KR) that is resistant to degradation, confirming that degradation is lysine-dependent. However, despite repeated attempts, no direct ubiquitylation of NSs in infected cells could be demonstrated. This suggests that degradation of NSs, although lysine-dependent, may be achieved through an indirect mechanism. Infection of cultured mammalian cells or mice indicated no disadvantage for the virus in having a non-degradable NSs protein: in fact rBUN4KR had a slight growth advantage over wtBUNV in interferon-competent cells, presumably due to the increased and prolonged presence of NSs. In cultured mosquito cells there was no difference in growth between wild-type BUNV and rBUN4KR, but surprisingly NSs4KR was not stabilised compared to the wild-type NSs protein.",2013 May 8,"['van Knippenberg, Ingeborg', 'Fragkoudis, Rennos', 'Elliott, Richard M.']",PLoS One,,,True
10c5b88204b337e7d05aceba5fc73d041153d0d3,PMC,"Viral Aetiology in Adults with Acute Upper Respiratory Tract Infection in Jinan, Northern China",http://dx.doi.org/10.1155/2013/869521,PMC3649347,23690828,CC BY,"Our study investigated the epidemiology of respiratory viruses in adult patients with upper respiratory tract infection (URTI) between August 2009 and September 2010 in Jinan, northern China. Nasal and throat swabs (n = 596) were collected from adult patients with URTIs. Nine respiratory-related viruses, including IFV, PIV, HRV, HMPV, HBoV, HCoV, ADV, RSV, and EV, were detected in all samples by conventional and reverse transcription polymerase chain reactions. Positive detection rate for respiratory virus was 38.76% and codetection rate was 4.70% in adults with acute respiratory tract infections. IFV (20.81%) was the dominant agent detected and IFVB had a higher incidence (12.58%) than IFVA (7.72%). Detection rates of 8.22%, 5.03%, 3.69%, and 2.52% were observed for HBoV, HRV, EV, and RSV, respectively. HCoV had the lowest detection rate of 0.50%. HBoV, HRV, EV, and ADV infection rates were higher in the 14–25-year-old group than in the 26–65-year-old group. Codetection rates were higher (7.52%) in the 14–25-year-old group than in the older age group (2.64%). The spectrum of respiratory virus infection in adult patients with URTIs was different in Jinan compared with other cities in China.",2013 Apr 15,"['Lu, Yanqin', 'Tong, Jiabei', 'Pei, Fengyan', 'Yang, Yanping', 'Xu, Dong', 'Ji, Mingyu', 'Xing, Chunyan', 'Jia, Pingdong', 'Xu, Chao', 'Wang, Yunshan', 'Li, Gongchao', 'Chai, Zhenbin', 'Liu, Yan', 'Han, Jinxiang']",Clin Dev Immunol,,,True
d392fcba605d12d5f9b3b31f6d0c620b6a89cdcc,PMC,Curcumin Nanoparticles Ameliorate ICAM-1 Expression in TNF-α-Treated Lung Epithelial Cells through p47 (phox) and MAPKs/AP-1 Pathways,http://dx.doi.org/10.1371/journal.pone.0063845,PMC3650060,23671702,CC BY,"Upregulation of intercellular adhesion molecule-1 (ICAM-1) involves adhesions between both circulating and resident leukocytes and the human lung epithelial cells during lung inflammatory reactions. We have previously demonstrated that curcumin-loaded polyvinylpyrrolidone nanoparticles (CURN) improve the anti-inflammatory and anti-oxidative properties of curcumin in hepatocytes. In this study, we focused on the effects of CURN on the expression of ICAM-1 in TNF-α-treated lung epithelial cells and compared these to the effects of curcumin water preparation (CURH). TNF-αinduced ICAM-1 expression, ROS production, and cell-cell adhesion were significantly attenuated by the pretreatment with antioxidants (DPI, APO, or NAC) and CURN, but not by CURH, as revealed by western blot analysis, RT-PCR, promoter assay, and ROS detection and adhesion assay. In addition, treatment of TNF-α-treated cells with CURN and antioxidants also resulted in an inhibition of activation of p47 (phox) and phosphorylation of MAPKs, as compared to that using CURH. Our findings also suggest that phosphorylation of MAPKs may eventually lead to the activation of transcription factors. We also observed that the effects of TNF-α treatment for 30 min, which includes a significant increase in the binding activity of AP-1 and phosphorylation of c-jun and c-fos genes, were reduced by CURN treatment. In vivo studies have revealed that CURN improved the anti-inflammation activities of CURH in the lung epithelial cells of TNF-α-treated mice. Our results indicate that curcumin-loaded polyvinylpyrrolidone nanoparticles may potentially serve as an anti-inflammatory drug for the treatment of respiratory diseases.",2013 May 9,"['Yen, Feng-Lin', 'Tsai, Ming-Horng', 'Yang, Chuen-Mao', 'Liang, Chan-Jung', 'Lin, Chun-Ching', 'Chiang, Yao-Chang', 'Lee, Hui-Chun', 'Ko, Horng-Huey', 'Lee, Chiang-Wen']",PLoS One,,,True
1536008edcc909523ffc39c62b8389ba0ee76f95,PMC,Pediatric Asthma Mortality and Hospitalization Trends Across Asia Pacific Relationship With Asthma Drug Utilization Patterns,http://dx.doi.org/10.1097/WOX.0b013e3181a7c288,PMC3651014,23283014,CC BY,"BACKGROUND: The wide variability in prevalence of childhood asthma across Asia Pacific is well documented, but less is known about its trends in mortality and hospitalization. OBJECTIVES: To examine pediatric asthma mortality and hospitalization trends of selected countries across Asia Pacific, and also patterns of asthma drug utilization. MATERIALS AND METHODS: Mortality and population data were sourced from the World Health Organization's mortality database. Data on hospitalization were obtained by direct inquiry and from government and scientific publications. Drug use for asthma was expressed as a controller-to-reliever (C:R) ratio (ie, units of inhaled corticosteroids/units of short-acting β-agonists, sold in each country). Time-series regression analyses were used to examine temporal patterns and study association between deaths, hospitalizations, and drug use. RESULTS: Japan showed a decreasing trend in pediatric asthma mortality whereas an increase was observed in Thailand. Hospitalizations decreased in Australia and Singapore but increased in Taiwan, Republic of China. C:R ratios increased significantly across the countries. CONCLUSIONS: Mixed trends in pediatric asthma mortality and hospitalization rates were observed, which coincided with a uniform increase in C:R ratios. This may reflect importance of other aspects of asthma management besides pharmacotherapy.",2009 May 15,"['Chua, Kun Lin', 'Soh, Shu E', 'Ma, Stefan', 'Lee, Bee Wah']",World Allergy Organ J,,,True
8ac43920461faa8a180d94acd6c5a6b35ab8bf7a,PMC,"History of the World Allergy Organization: 1989 to 2006, the XVIII World Allergy Congress, Journal Development, Reorganization, and New Programs",http://dx.doi.org/10.1097/WOX.0b013e31822c9540,PMC3651123,23282542,CC BY,"History of the World Allergy Organization: In 1951, the leaders in allergy from all over the world came together to form the International Association of Allergology and Clinical Immunology (IAACI). For the next 60 years, the allergy world converged at the IAACI triennial meetings, which became biennial in 2003. The international meetings, originally named the International Congress of Allergology and Clinical Immunology (ICACI), are now the World Allergy Congress (WAC) hosted by the World Allergy Organization (WAO). Everyone who has aspired to have worldwide recognition has played a part in IAACI-WAO. The History of the WAO traces the global arc of the allergy field over the past 60 years. The current officers of WAO elected to focus on this rich history, inviting prominent leaders who are interested in being part of this history project to write about their time with IAACI-WAO. This series will be presented in Cancún, México, as part of the XXII World Allergy Congress (December 4-8, 2011). Leading up to the Congress in Cancún, the WAO Journal is presenting segments of the History as part of the ""Notes of Allergy Watchers Series."" Please enjoy. --Michael A. Kaliner, MD Historian, and Past-President (2006-2007), World Allergy Organization",2011 Aug 15,"Kaplan, Allen P",World Allergy Organ J,,,False
52c813a9ed6582f44ae9b23fbb625e0f5a1b7365,PMC,A mobile genetic element with unknown function found in distantly related viruses,http://dx.doi.org/10.1186/1743-422X-10-132,PMC3653767,23618040,CC BY,"BACKGROUND: The genetic element s2m seems to represent one of very few examples of mobile genetic elements in viruses. The function remains obscure and a scattered taxonomical distribution has been reported by numerous groups. METHODS: We have searched GenBank in order to identify all viral accessions that have s2m(−like) sequence motifs. Rigorous phylogenetic analyses and constrained tree topology testing were also performed in order to investigate the apparently mobile nature of s2m. RESULTS: The stem-loop s2m structure can be found in four families of + ssRNA viruses; Astroviridae, Caliciviridae, Picornaviridae and Coronaviridae. In all of these virus families, with the possible exception of Caliciviridae, multiple gains and/or losses of s2m would have to be postulated in order to explain the distribution of this character. CONCLUSIONS: s2m appears to be a mobile genetic element with a unique evolutionary history in all of the four virus families where it can be found. Based on our findings and a review of the current literature on s2m, a hypothesis implying an RNAi-like function for the s2m element is also outlined.",2013 Apr 25,"['Tengs, Torstein', 'Kristoffersen, Anja Bråthen', 'Bachvaroff, Tsvetan R', 'Jonassen, Christine Monceyron']",Virol J,,,True
62a67d1f86138972ae0d79681ddd2a4a75f6dec0,PMC,Carriage of Mycoplasma pneumoniae in the Upper Respiratory Tract of Symptomatic and Asymptomatic Children: An Observational Study,http://dx.doi.org/10.1371/journal.pmed.1001444,PMC3653782,23690754,CC BY,"BACKGROUND: Mycoplasma pneumoniae is thought to be a common cause of respiratory tract infections (RTIs) in children. The diagnosis of M. pneumoniae RTIs currently relies on serological methods and/or the detection of bacterial DNA in the upper respiratory tract (URT). It is conceivable, however, that these diagnostic methods also yield positive results if M. pneumoniae is carried asymptomatically in the URT. Positive results from these tests may therefore not always be indicative of a symptomatic infection. The existence of asymptomatic carriage of M. pneumoniae has not been established. We hypothesized that asymptomatic carriage in children exists and investigated whether colonization and symptomatic infection could be differentiated by current diagnostic methods. METHODS AND FINDINGS: This study was conducted at the Erasmus MC–Sophia Children's Hospital and the after-hours General Practitioners Cooperative in Rotterdam, The Netherlands. Asymptomatic children (n = 405) and children with RTI symptoms (n = 321) aged 3 mo to 16 y were enrolled in a cross-sectional study from July 1, 2008, to November 30, 2011. Clinical data, pharyngeal and nasopharyngeal specimens, and serum samples were collected. The primary objective was to differentiate between colonization and symptomatic infection with M. pneumoniae by current diagnostic methods, especially real-time PCR. M. pneumoniae DNA was detected in 21.2% (95% CI 17.2%–25.2%) of the asymptomatic children and in 16.2% (95% CI 12.2%–20.2%) of the symptomatic children (p = 0.11). Neither serology nor quantitative PCR nor culture differentiated asymptomatic carriage from infection. A total of 202 children were tested for the presence of other bacterial and viral pathogens. Two or more pathogens were found in 56% (63/112) of the asymptomatic children and in 55.5% (50/90) of the symptomatic children. Finally, longitudinal sampling showed persistence of M. pneumoniae in the URT for up to 4 mo. Fifteen of the 21 asymptomatic children with M. pneumoniae and 19 of the 22 symptomatic children with M. pneumoniae in this longitudinal follow-up tested negative after 1 mo. CONCLUSIONS: Although our study has limitations, such as a single study site and limited sample size, our data indicate that the presence of M. pneumoniae in the URT is common in asymptomatic children. The current diagnostic tests for M. pneumoniae are unable to differentiate between asymptomatic carriage and symptomatic infection. Please see later in the article for the Editors' Summary",2013 May 14,"['Spuesens, Emiel B. M.', 'Fraaij, Pieter L. A.', 'Visser, Eline G.', 'Hoogenboezem, Theo', 'Hop, Wim C. J.', 'van Adrichem, Léon N. A.', 'Weber, Frank', 'Moll, Henriette A.', 'Broekman, Berth', 'Berger, Marjolein Y.', 'van Rijsoort-Vos, Tineke', 'van Belkum, Alex', 'Schutten, Martin', 'Pas, Suzan D.', 'Osterhaus, Albert D. M. E.', 'Hartwig, Nico G.', 'Vink, Cornelis', 'van Rossum, Annemarie M. C.']",PLoS Med,,,True
07396bda4a37d13aaf15fdf67d61971549f4162c,PMC,"Viral Etiology of Acute Respiratory Infection in Gansu Province, China, 2011",http://dx.doi.org/10.1371/journal.pone.0064254,PMC3653869,23691184,CC BY,"BACKGROUND: Acute respiratory infections (ARIs) are the leading cause of children and their leading killer. ARIs are responsible for at least six percent of the world's disability and death. Viruses are one of the most common agents causing ARIs. Few studies on the viral etiology and clinical characteristics of ARIs have been performed in the northwest region of China, including Gansu Province. METHODS: Clinical and demographic information and throat swabs were collected from 279 patients from January 1st to December 30st, 2011. Multiplex RT-PCR was performed to detect 16 respiratory viral pathogens. RESULTS: 279 patients were admitted for ARIs. The patients aged from 1 month to 12 years, with the median age of 2 years. Of which, 105 (37.6%) were positive for at least one pathogen. A total of 136 respiratory viral pathogens were identified from the 105 patients. Respiratory syncytial virus (RSV) was the most frequently detected pathogen (26.5%, 36/136), followed by parainfluenza virus (PIV) 1–3 (22.1%, 30/136), human rhinovirus (HRV) (21.3%, 29/136), human coronavirus (CoV) (10.3%, 14/136) and human adenovirus (HAdV) (9.6%, 13/136). Influenza A (Flu A), human metapneumovirus (hMPV) and human bocavirus (BoCA) were found 4.4%, 3.7% and 2.2%, respectively. Influenza B (Flu B) and seasonal influenza A H1N1(sH1N1) were not detected. Single-infections were detected in 30.5% (85/279) of cases. RSV was the most common pathogens in patients under 1 year and showed seasonal variation with peaks during winter and spring. CONCLUSIONS: This paper presents data on the epidemiology of viral pathogens associated with ARIs among children in Gansu Province, China. RSV is most frequently detected in our study. The findings could serve as a reference for local CDC in drawing up further plans to prevent and control ARIs.",2013 May 14,"['Huang, Guohong', 'Yu, Deshan', 'Mao, Naiying', 'Zhu, Zhen', 'Zhang, Hui', 'Jiang, Zhongyi', 'Li, Hongyu', 'Zhang, Yan', 'Shi, Jing', 'Zhang, Shuang', 'Wang, Xinhua', 'Xu, Wenbo']",PLoS One,,,True
6fcc000ecf39dd1da69d94d8cd764790ce96aaba,PMC,Recombinant Vaccines against T. gondii: Comparison between Homologous and Heterologous Vaccination Protocols Using Two Viral Vectors Expressing SAG1,http://dx.doi.org/10.1371/journal.pone.0063201,PMC3654925,23690999,CC BY,"The use of recombinant viral vectors expressing T. gondii antigens is a safe and efficient approach to induce immune response against the parasite and a valuable tool for vaccine development. We have previously protected mice from toxoplasmosis by immunizing the animals with an adenovirus expressing the protein SAG1 (AdSAG1) of T. gondii. We are now looking for ways to improve the vaccination strategy and enhance protection. One limitation of homologous vaccinations (sequential doses of the same vector) is induction of anti-vector immune response that blocks cell transduction, restricts transgene expression and, consequently, compromises the overall outcome of vaccination. One way to avert the effects of anti-vector response is to use different viruses in prime and boost (heterologous vaccination). Bearing this in mind, we generated a modified Vaccinia Virus Ankara encoding SAG1 (MVASAG1), to be tested as boost agent after prime with AdSAG1. Although minor differences were observed in the magnitude of the anti-SAG1 immune response induced by each vaccination protocol, the heterologous immunization with AdSAG1 followed by MVASAG1 resulted in improved capacity to control brain cyst formation in a model of chronic toxoplasmosis in C57BL/6 mice.",2013 May 15,"['Mendes, Érica Araújo', 'Fonseca, Flavio G.', 'Casério, Bárbara M.', 'Colina, Janaína P.', 'Gazzinelli, Ricardo Tostes', 'Caetano, Braulia C.']",PLoS One,,,True
921a97ffd33121fd2623fb899b386adce87a8562,PMC,"Epidemiological analysis of respiratory viral etiology for influenza-like illness during 2010 in Zhuhai, China",http://dx.doi.org/10.1186/1743-422X-10-143,PMC3655035,23651577,CC BY,"BACKGROUND: Influenza-like illnesses (ILI), a subset of acute respiratory infections (ARI), are a significant source of morbidity and mortality worldwide. ILI can be caused by numerous pathogens, however; there is limited information on the etiology and epidemiology of ILI in China. METHODS: We performed a one-year surveillance study (2010) of viral etiology causing ILI and investigated the influence of climate on outbreaks of ILI attributed to viruses at the Outpatient Department of Zhuhai Municipal People’s Hospital in Zhuhai, China. RESULTS: Of the 337,272 outpatients who sought attention in the Outpatient Department of Zhuhai Municipal People’s Hospital in 2010, 3,747 (1.11%) presented with ILI. Of these patients presenting with ILI, 24.66% (924/3,747) had available samples and were enrolled in this study. At least one respiratory virus was identified in 411 patients (44.48%) and 42 (4.55%) were co-infected with two viruses. In patients co-infected with two viruses, respiratory syncytial virus (RSV) was detected in 50% (21/42). Among common viral pathogens detected, significant differences in age distributions were observed in seasonal influenza virus A (sFulA, H3N2) and B (sFluB), pandemic H1N1 2009 influenza viruses (H1N1pdm09), RSV, and adenovirus (ADV). Infections with sFluA (H3N2), sFluB, RSV, and human metapneumovirus (HMPV) had characteristic seasonal patterns. The incidences of sFluA (H3N2), ADV, and RSV correlated with air temperature. Alternatively, the incidence of sFluB correlated with relative air humidity. CONCLUSIONS: These results demonstrate that a wide range of respiratory viral pathogens are circulating in Zhuhai city. This information needs to be considered by clinicians when treating patients presenting with ILI.",2013 May 7,"['Li, Hongxia', 'Wei, Quande', 'Tan, Aijun', 'Wang, Leyi']",Virol J,,,True
43ea5663d460f9bc3ec53ceea11e85b6265a1fef,PMC,New Insights in Recurrent HCV Infection after Liver Transplantation,http://dx.doi.org/10.1155/2013/890517,PMC3655463,23710205,CC BY,"Hepatitis C virus (HCV) is a small-enveloped RNA virus belonging to the Flaviviridae family. Since first identified in 1989, HCV has been estimated to infect 170 million people worldwide. Mostly chronic hepatitis C virus has a uniform natural history, from liver cirrhosis to the development of hepatocellular carcinoma. The current therapy for HCV infection consists of a combination of Pegylated interferon and ribavirin. On the other hand, HCV-related liver disease is also the leading indication for liver transplantation. However, posttransplant HCV re-infection of the graft has been reported to be universal. Furthermore, the graft after HCV re-infection often results in accelerated progression to liver failure. In addition, treatment of recurrent HCV infection after liver transplantation is often compromised by enhanced adverse effects and limited efficacy of interferon-based therapies. Taken together, poor outcome after HCV re-infection, regardless of grafts or recipients, poses a major issue for the hepatologists and transplant surgeons. The aim of this paper is to review several specific aspects regarding HCV re-infection after transplant: risk factors, current therapeutics for HCV in different stages of liver transplantation, cellular function of HCV proteins, and molecular mechanisms of HCV entry. Hopefully, this paper will inspire new strategies and novel inhibitors against recurrent HCV infection after liver transplantation and greatly improve its overall outcome.",2013 Apr 23,"['Hsu, Shih-Hsien', 'Yeh, Ming-Lun', 'Wang, Shen-Nien']",Clin Dev Immunol,,,True
aef63bcba33e2bc1d7a7f1c3e71d7313e2769d98,PMC,Conditional ligands for Asian HLA variants facilitate the definition of CD8(+) T-cell responses in acute and chronic viral diseases,http://dx.doi.org/10.1002/eji.201243088,PMC3655610,23280567,CC BY,"Conditional ligands have enabled the high-throughput production of human leukocyte antigen (HLA) libraries that present defined peptides. Immunomonitoring platforms typically concentrate on restriction elements associated with European ancestry, and such tools are scarce for Asian HLA variants. We report 30 novel irradiation-sensitive ligands, specifically targeting South East Asian populations, which provide 93, 63, and 79% coverage for HLA-A, -B, and -C, respectively. Unique ligands for all 16 HLA types were constructed to provide the desired soluble HLA product in sufficient yield. Peptide exchange was accomplished for all variants as demonstrated by an ELISA-based MHC stability assay. HLA tetramers with redirected specificity could detect antigen-specific CD8(+) T-cell responses against human cytomegalovirus, hepatitis B (HBV), dengue virus (DENV), and Epstein-Barr virus (EBV) infections. The potential of this population-centric HLA library was demonstrated with the characterization of seven novel T-cell epitopes from severe acute respiratory syndrome coronavirus, HBV, and DENV. Posthoc analysis revealed that the majority of responses would be more readily identified by our unbiased discovery approach than through the application of state-of-the-art epitope prediction. This flow cytometry-based technology therefore holds considerable promise for monitoring clinically relevant antigen-specific T-cell responses in populations of distinct ethnicity.",2013 Apr 26,"['Chang, Cynthia X L', 'Tan, Anthony T', 'Or, Ming Yan', 'Toh, Kai Yee', 'Lim, Pei Yiing', 'Chia, Adeline S E', 'Froesig, Thomas M', 'Nadua, Karen D', 'Oh, Hsueh-Ling J', 'Leong, Hoe Nam', 'Hadrup, Sine R', 'Gehring, Adam J', 'Tan, Yee-Joo', 'Bertoletti, Antonio', 'Grotenbreg, Gijsbert M']",Eur J Immunol,,,True
fac9ef6ba1ca4bdb16baad83f0146e6a5c3b906f,PMC,Conditional ligands for Asian HLA variants facilitate the definition of CD8(+) T-cell responses in acute and chronic viral diseases,http://dx.doi.org/10.1002/eji.201243088,PMC3655610,23280567,CC BY,"Conditional ligands have enabled the high-throughput production of human leukocyte antigen (HLA) libraries that present defined peptides. Immunomonitoring platforms typically concentrate on restriction elements associated with European ancestry, and such tools are scarce for Asian HLA variants. We report 30 novel irradiation-sensitive ligands, specifically targeting South East Asian populations, which provide 93, 63, and 79% coverage for HLA-A, -B, and -C, respectively. Unique ligands for all 16 HLA types were constructed to provide the desired soluble HLA product in sufficient yield. Peptide exchange was accomplished for all variants as demonstrated by an ELISA-based MHC stability assay. HLA tetramers with redirected specificity could detect antigen-specific CD8(+) T-cell responses against human cytomegalovirus, hepatitis B (HBV), dengue virus (DENV), and Epstein-Barr virus (EBV) infections. The potential of this population-centric HLA library was demonstrated with the characterization of seven novel T-cell epitopes from severe acute respiratory syndrome coronavirus, HBV, and DENV. Posthoc analysis revealed that the majority of responses would be more readily identified by our unbiased discovery approach than through the application of state-of-the-art epitope prediction. This flow cytometry-based technology therefore holds considerable promise for monitoring clinically relevant antigen-specific T-cell responses in populations of distinct ethnicity.",2013 Apr 26,"['Chang, Cynthia X L', 'Tan, Anthony T', 'Or, Ming Yan', 'Toh, Kai Yee', 'Lim, Pei Yiing', 'Chia, Adeline S E', 'Froesig, Thomas M', 'Nadua, Karen D', 'Oh, Hsueh-Ling J', 'Leong, Hoe Nam', 'Hadrup, Sine R', 'Gehring, Adam J', 'Tan, Yee-Joo', 'Bertoletti, Antonio', 'Grotenbreg, Gijsbert M']",Eur J Immunol,,,True
ee06cad1229867a6389ed8a7aaffb5148dd5f8ed,PMC,Conditional ligands for Asian HLA variants facilitate the definition of CD8(+) T-cell responses in acute and chronic viral diseases,http://dx.doi.org/10.1002/eji.201243088,PMC3655610,23280567,CC BY,"Conditional ligands have enabled the high-throughput production of human leukocyte antigen (HLA) libraries that present defined peptides. Immunomonitoring platforms typically concentrate on restriction elements associated with European ancestry, and such tools are scarce for Asian HLA variants. We report 30 novel irradiation-sensitive ligands, specifically targeting South East Asian populations, which provide 93, 63, and 79% coverage for HLA-A, -B, and -C, respectively. Unique ligands for all 16 HLA types were constructed to provide the desired soluble HLA product in sufficient yield. Peptide exchange was accomplished for all variants as demonstrated by an ELISA-based MHC stability assay. HLA tetramers with redirected specificity could detect antigen-specific CD8(+) T-cell responses against human cytomegalovirus, hepatitis B (HBV), dengue virus (DENV), and Epstein-Barr virus (EBV) infections. The potential of this population-centric HLA library was demonstrated with the characterization of seven novel T-cell epitopes from severe acute respiratory syndrome coronavirus, HBV, and DENV. Posthoc analysis revealed that the majority of responses would be more readily identified by our unbiased discovery approach than through the application of state-of-the-art epitope prediction. This flow cytometry-based technology therefore holds considerable promise for monitoring clinically relevant antigen-specific T-cell responses in populations of distinct ethnicity.",2013 Apr 26,"['Chang, Cynthia X L', 'Tan, Anthony T', 'Or, Ming Yan', 'Toh, Kai Yee', 'Lim, Pei Yiing', 'Chia, Adeline S E', 'Froesig, Thomas M', 'Nadua, Karen D', 'Oh, Hsueh-Ling J', 'Leong, Hoe Nam', 'Hadrup, Sine R', 'Gehring, Adam J', 'Tan, Yee-Joo', 'Bertoletti, Antonio', 'Grotenbreg, Gijsbert M']",Eur J Immunol,,,True
b3e7a3736c037ca082235e695e686cce2a4790a1,PMC,The Secret Life of Viral Entry Glycoproteins: Moonlighting in Immune Evasion,http://dx.doi.org/10.1371/journal.ppat.1003258,PMC3656028,23696729,CC BY,,2013 May 16,"['Cook, Jonathan D.', 'Lee, Jeffrey E.']",PLoS Pathog,,,True
74f36e3fdaac0583dace5a4a9031bc79d154c798,PMC,Abortive Lytic Reactivation of KSHV in CBF1/CSL Deficient Human B Cell Lines,http://dx.doi.org/10.1371/journal.ppat.1003336,PMC3656114,23696732,CC BY,"Since Kaposi's sarcoma associated herpesvirus (KSHV) establishes a persistent infection in human B cells, B cells are a critical compartment for viral pathogenesis. RTA, the replication and transcription activator of KSHV, can either directly bind to DNA or use cellular DNA binding factors including CBF1/CSL as DNA adaptors. In addition, the viral factors LANA1 and vIRF4 are known to bind to CBF1/CSL and modulate RTA activity. To analyze the contribution of CBF1/CSL to reactivation in human B cells, we have successfully infected DG75 and DG75 CBF1/CSL knock-out cell lines with recombinant KSHV.219 and selected for viral maintenance by selective medium. Both lines maintained the virus irrespective of their CBF1/CSL status. Viral reactivation could be initiated in both B cell lines but viral genome replication was attenuated in CBF1/CSL deficient lines, which also failed to produce detectable levels of infectious virus. Induction of immediate early, early and late viral genes was impaired in CBF1/CSL deficient cells at multiple stages of the reactivation process but could be restored to wild-type levels by reintroduction of CBF1/CSL. To identify additional viral RTA target genes, which are directly controlled by CBF1/CSL, we analyzed promoters of a selected subset of viral genes. We show that the induction of the late viral genes ORF29a and ORF65 by RTA is strongly enhanced by CBF1/CSL. Orthologs of ORF29a in other herpesviruses are part of the terminase complex required for viral packaging. ORF65 encodes the small capsid protein essential for capsid shell assembly. Our study demonstrates for the first time that in human B cells viral replication can be initiated in the absence of CBF1/CSL but the reactivation process is severely attenuated at all stages and does not lead to virion production. Thus, CBF1/CSL acts as a global hub which is used by the virus to coordinate the lytic cascade.",2013 May 16,"['Scholz, Barbara A.', 'Harth-Hertle, Marie L.', 'Malterer, Georg', 'Haas, Juergen', 'Ellwart, Joachim', 'Schulz, Thomas F.', 'Kempkes, Bettina']",PLoS Pathog,,,True
a13c79aab29bf6afdf2fe0cbd6269b1941e77ee0,PMC,"Risk Perception, Preventive Behaviors, and Vaccination Coverage in the Korean Population during the 2009–2010 Pandemic Influenza A (H1N1): Comparison between High-Risk Group and Non–High-Risk Group",http://dx.doi.org/10.1371/journal.pone.0064230,PMC3656839,23691175,CC BY,"BACKGROUND: This study was carried out to estimate the vaccination coverage, public perception, and preventive behaviors against pandemic influenza A (H1N1) and to understand the motivation and barriers to vaccination between high-risk and non–high-risk groups during the outbreak of pandemic influenza A (H1N1). METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional nationwide telephone survey of 1,650 community-dwelling Korean adults aged 19 years and older was conducted in the later stage of the 2009–2010 pandemic influenza A (H1N1) outbreak. The questionnaire identified the demographics, vaccination status of participants and all household members, barriers to non-vaccination, perceived threat, and preventive behaviors. In Korea, the overall rate of pandemic influenza vaccination coverage in the surveyed population was 15.5%; vaccination coverage in the high-risk group and non–high-risk group was 47.3% and 8.0%, respectively. In the high-risk group, the most important triggering event for vaccination was receiving a notice from a public health organization. In the non–high-risk group, vaccination was more strongly influenced by previous experience with influenza or mass media campaigns. In both groups, the most common reasons for not receiving vaccination was that their health was sufficient to forgo the vaccination, and lack of time. There was no significant difference in how either group perceived the threat or adopted preventive behavior. The predictive factors for pandemic influenza vaccination were being elderly (age ≥65 years), prior seasonal influenza vaccination, and chronic medical disease. CONCLUSIONS/SIGNIFICANCE: With the exception of vaccination coverage, the preventive behaviors of the high-risk group were not different from those of the non–high-risk group during the 2009–2010 pandemic. For future pandemic preparedness planning, it is crucial to reinforce preventive behaviors to avoid illness before vaccination and to increase vaccination coverage in the high-risk group.",2013 May 17,"['Heo, Jung Yeon', 'Chang, Soung Hoon', 'Go, Min Jung', 'Kim, Young Mee', 'Gu, Sun Hye', 'Chun, Byung Chul']",PLoS One,,,True
2fc84e709c4978a92c3f4168a6c145080d1b046b,PMC,Presence of Infectious Bronchitis Virus Strain CK/CH/LDL/97I in the Middle East,http://dx.doi.org/10.5402/2012/201721,PMC3658599,23738118,CC BY,"Infectious bronchitis virus (IBV) is a very dynamic and evolving virus, causing major economic losses to the global poultry industry. In early 2011, respiratory disease outbreaks were investigated in Iraq, Jordan, and Saudi Arabia. Five IBV isolates (JOA2, JOA4, Saudi-1, Saudi-2, and Iraqi IBV) were detected by diagnostic-nested nucleocapsid RT-PCR. Strain identification was characterised by sequencing and phylogenetic analysis of the amplified hypervariable region of the spike 1 (S1) gene. These five IBV isolates were found to be of the IBV strain CK/CH/LDL/97I. Nucleotide identity between these five IBV isolates ranged from 96.9% to 99.7%, and between these isolates and the CK/CH/LDL/97I strain in the range of 96.6–99.1%. The sequenced fragment of the S1 gene of the CK/CH/LDL/97I strain had less than 80% nucleotide identity to the IBV vaccine strains commonly used in the Middle East (M41 and H120). The presence of these CK/CH/LDL/97I-like strains may account for vaccination failure against IBV, since all IBV isolates were from vaccinated chickens. In this paper, we documented for the first time the presence of IBV strain CK/CH/LDL/97I in the Middle East. This strain is known to have originated in China and Taiwan.",2012 Apr 11,"['Ababneh, Mustafa', 'Dalab, Abd Elhafeed', 'Alsaad, Saad', 'Al-Zghoul, Mohammad']",ISRN Vet Sci,,,True
7f302add8b117514b8393d55f49c3ded276faf94,PMC,"Rapid, responsive, relevant (R3) research: a call for a rapid learning health research enterprise",http://dx.doi.org/10.1186/2001-1326-2-10,PMC3658895,23663660,CC BY,"Our current health research enterprise is painstakingly slow and cumbersome, and its results seldom translate into practice. The slow pace of health research contributes to findings that are less relevant and potentially even obsolete. To produce more rapid, responsive, and relevant research, we propose approaches that increase relevance via greater stakeholder involvement, speed research via innovative designs, streamline review processes, and create and/or better leverage research infrastructure. Broad stakeholder input integrated throughout the research process can both increase relevance and facilitate study procedures. More flexible and rapid research designs should be considered before defaulting to the traditional two-arm randomized controlled trial (RCT), but even traditional RCTs can be designed for more rapid findings. Review processes for grant applications, IRB protocols, and manuscript submissions can be better streamlined to minimize delays. Research infrastructures such as rapid learning systems and other health information technologies can be leveraged to rapidly evaluate new and existing treatments, and alleviate the extensive recruitment delays common in traditional research. These and other approaches are feasible but require a culture shift among the research community to value not only methodological rigor, but also the pace and relevance of research.",2013 May 10,"['Riley, William T', 'Glasgow, Russell E', 'Etheredge, Lynn', 'Abernethy, Amy P']",Clin Transl Med,,,True
04799a6c57e1d3f9488b24a4fc2580bbb3818665,PMC,Development of porcine rotavirus vp6 protein based ELISA for differentiation of this virus and other viruses,http://dx.doi.org/10.1186/1743-422X-10-91,PMC3658953,23517810,CC BY,"BACKGROUND: The context and purpose of the study included 1) bacterial expression of viral protein 6 (VP6) of porcine rotavirus (PRV) and generation of rabbit polyclonal antiserum to the VP6 protein; 3) establishment of a discrimination ELISA to distinguish PRV from a panel of other porcine viruses. RESULTS: The VP6 gene of PRV isolate DN30209 amplified by reverse transcription-PCR was 1356 bp containing a complete open reading frame (ORF) encoding 397 amino acids. Sequence comparison and phylogenetic analysis indicated that PRV DN30209 may belong to group A of rotavirus. Bacterially expressed VP6 was expressed in E.coli and anti-VP6 antibody was capable of distinguishing PRV from Porcine transmissible gastroenteritis virus, Porcine epidemic diarrhea virus, Porcine circovirus type II, Porcine reproductive and respiratory syndrome virus, Porcine pseudorabies virus and Porcine parvovirus. CONCLUSIONS: PRV VP6 expressed in E. coli can be used to generate antibodies in rabbit; anti-VP6 serum antibody can be used as good diagnostic reagents for detection of PRV.",2013 Mar 22,"['Zhu, Jiayi', 'Yang, Qing', 'Cao, Liyan', 'Dou, Xiujing', 'Zhao, Jianguo', 'Zhu, Weijuan', 'Ding, Fan', 'Bu, Ri-e', 'Suo, Siqingaowa', 'Ren, Yudong', 'Li, Guangxing', 'Ren, Xiaofeng']",Virol J,,,True
b58b4809e706401c8f5851d5b0d2be93b8f431cf,PMC,Ecological Factors Associated with European Bat Lyssavirus Seroprevalence in Spanish Bats,http://dx.doi.org/10.1371/journal.pone.0064467,PMC3659107,23700480,CC0,"Bats have been proposed as major reservoirs for diverse emerging infectious viral diseases, with rabies being the best known in Europe. However, studies exploring the ecological interaction between lyssaviruses and their natural hosts are scarce. This study completes our active surveillance work on Spanish bat colonies that began in 1992. Herein, we analyzed ecological factors that might affect the infection dynamics observed in those colonies. Between 2001 and 2011, we collected and tested 2,393 blood samples and 45 dead bats from 25 localities and 20 bat species. The results for dead confirmed the presence of EBLV-1 RNA in six species analyzed (for the first time in Myotis capaccinii). Samples positive for European bat lyssavirus-1 (EBLV-1)–neutralizing antibodies were detected in 68% of the localities sampled and in 13 bat species, seven of which were found for the first time (even in Myotis daubentonii, a species to date always linked to EBLV-2). EBLV-1 seroprevalence (20.7%) ranged between 11.1 and 40.2% among bat species and seasonal variation was observed, with significantly higher antibody prevalence in summer (July). EBLV-1 seroprevalence was significantly associated with colony size and species richness. Higher seroprevalence percentages were found in large multispecific colonies, suggesting that intra- and interspecific contacts are major risk factors for EBLV-1 transmission in bat colonies. Although bat-roosting behavior strongly determines EBLV-1 variability, we also found some evidence that bat phylogeny might be involved in bat-species seroprevalence. The results of this study highlight the importance of life history and roost ecology in understanding EBLV-1–prevalence patterns in bat colonies and also provide useful information for public health officials.",2013 May 20,"['Serra-Cobo, Jordi', 'López-Roig, Marc', 'Seguí, Magdalena', 'Sánchez, Luisa Pilar', 'Nadal, Jacint', 'Borrás, Miquel', 'Lavenir, Rachel', 'Bourhy, Hervé']",PLoS One,,,True
0ba1801a150e25b029cf3c2a38573435b21dea80,PMC,Identifying SARS-CoV Membrane Protein Amino Acid Residues Linked to Virus-Like Particle Assembly,http://dx.doi.org/10.1371/journal.pone.0064013,PMC3659117,23700447,CC BY,"Severe acute respiratory syndrome coronavirus (SARS-CoV) membrane (M) proteins are capable of self-assembly and release in the form of membrane-enveloped vesicles, and of forming virus-like particles (VLPs) when coexpressed with SARS-CoV nucleocapsid (N) protein. According to previous deletion analyses, M self-assembly involves multiple M sequence regions. To identify important M amino acid residues for VLP assembly, we coexpressed N with multiple M mutants containing substitution mutations at the amino-terminal ectodomain, carboxyl-terminal endodomain, or transmembrane segments. Our results indicate that a dileucine motif in the endodomain tail (218LL219) is required for efficient N packaging into VLPs. Results from cross-linking VLP analyses suggest that the cysteine residues 63, 85 and 158 are not in close proximity to the M dimer interface. We noted a significant reduction in M secretion due to serine replacement for C158, but not for C63 or C85. Further analysis suggests that C158 is involved in M-N interaction. In addition to mutations of the highly conserved 107-SWWSFNPE-114 motif, substitutions at codons W19, W57, P58, W91, Y94 or F95 all resulted in significantly reduced VLP yields, largely due to defective M secretion. VLP production was not significantly affected by a tryptophan replacement of Y94 or F95 or a phenylalanine replacement of W19, W57 or W91. Combined, these results indicate the involvement of specific M amino acids during SARS-CoV virus assembly, and suggest that aromatic residue retention at specific positions is critical for M function in terms of directing virus assembly.",2013 May 20,"['Tseng, Ying-Tzu', 'Chang, Chia-Hui', 'Wang, Shiu-Mei', 'Huang, Kuo-Jung', 'Wang, Chin-Tien']",PLoS One,,,True
e64c852725ef6bf2abf9071b522c10917b50ac6e,PMC,Platelet activation suppresses HIV-1 infection of T cells,http://dx.doi.org/10.1186/1742-4690-10-48,PMC3660175,23634812,CC BY,"BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.",2013 May 1,"['Solomon Tsegaye, Theodros', 'Gnirß, Kerstin', 'Rahe-Meyer, Niels', 'Kiene, Miriam', 'Krämer-Kühl, Annika', 'Behrens, Georg', 'Münch, Jan', 'Pöhlmann, Stefan']",Retrovirology,,,True
94becb8706cfe183f2debc7f9067513974a1a552,PMC,Platelet activation suppresses HIV-1 infection of T cells,http://dx.doi.org/10.1186/1742-4690-10-48,PMC3660175,23634812,CC BY,"BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.",2013 May 1,"['Solomon Tsegaye, Theodros', 'Gnirß, Kerstin', 'Rahe-Meyer, Niels', 'Kiene, Miriam', 'Krämer-Kühl, Annika', 'Behrens, Georg', 'Münch, Jan', 'Pöhlmann, Stefan']",Retrovirology,,,False
419a452d263cb907fb5c6b3e47c96aebabb78d64,PMC,Platelet activation suppresses HIV-1 infection of T cells,http://dx.doi.org/10.1186/1742-4690-10-48,PMC3660175,23634812,CC BY,"BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.",2013 May 1,"['Solomon Tsegaye, Theodros', 'Gnirß, Kerstin', 'Rahe-Meyer, Niels', 'Kiene, Miriam', 'Krämer-Kühl, Annika', 'Behrens, Georg', 'Münch, Jan', 'Pöhlmann, Stefan']",Retrovirology,,,False
145a6aff8c6d58f46bb0eb5671a9cabae0d939fc,PMC,Platelet activation suppresses HIV-1 infection of T cells,http://dx.doi.org/10.1186/1742-4690-10-48,PMC3660175,23634812,CC BY,"BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.",2013 May 1,"['Solomon Tsegaye, Theodros', 'Gnirß, Kerstin', 'Rahe-Meyer, Niels', 'Kiene, Miriam', 'Krämer-Kühl, Annika', 'Behrens, Georg', 'Münch, Jan', 'Pöhlmann, Stefan']",Retrovirology,,,False
14f9f4f16ad081a427b8f39d7fabe109c85acb9b,PMC,Platelet activation suppresses HIV-1 infection of T cells,http://dx.doi.org/10.1186/1742-4690-10-48,PMC3660175,23634812,CC BY,"BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.",2013 May 1,"['Solomon Tsegaye, Theodros', 'Gnirß, Kerstin', 'Rahe-Meyer, Niels', 'Kiene, Miriam', 'Krämer-Kühl, Annika', 'Behrens, Georg', 'Münch, Jan', 'Pöhlmann, Stefan']",Retrovirology,,,False
d6225b3ffed6a2077e3334b06526faa8b977182a,PMC,Platelet activation suppresses HIV-1 infection of T cells,http://dx.doi.org/10.1186/1742-4690-10-48,PMC3660175,23634812,CC BY,"BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.",2013 May 1,"['Solomon Tsegaye, Theodros', 'Gnirß, Kerstin', 'Rahe-Meyer, Niels', 'Kiene, Miriam', 'Krämer-Kühl, Annika', 'Behrens, Georg', 'Münch, Jan', 'Pöhlmann, Stefan']",Retrovirology,,,False
a96ad20c7fe3d4b57fc694c5957fa0404091f3de,PMC,Platelet activation suppresses HIV-1 infection of T cells,http://dx.doi.org/10.1186/1742-4690-10-48,PMC3660175,23634812,CC BY,"BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.",2013 May 1,"['Solomon Tsegaye, Theodros', 'Gnirß, Kerstin', 'Rahe-Meyer, Niels', 'Kiene, Miriam', 'Krämer-Kühl, Annika', 'Behrens, Georg', 'Münch, Jan', 'Pöhlmann, Stefan']",Retrovirology,,,False
d6a600b3dbaf7490b4b1fd35165333b03f7f2151,PMC,Platelet activation suppresses HIV-1 infection of T cells,http://dx.doi.org/10.1186/1742-4690-10-48,PMC3660175,23634812,CC BY,"BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.",2013 May 1,"['Solomon Tsegaye, Theodros', 'Gnirß, Kerstin', 'Rahe-Meyer, Niels', 'Kiene, Miriam', 'Krämer-Kühl, Annika', 'Behrens, Georg', 'Münch, Jan', 'Pöhlmann, Stefan']",Retrovirology,,,False
0cd911d564b693ebedf57fa37c28b8ea5705c174,PMC,"Laboratory Surveillance of Influenza-Like Illness in Seven Teaching Hospitals, South Korea: 2011–2012 Season",http://dx.doi.org/10.1371/journal.pone.0064295,PMC3661466,23717587,CC BY,"BACKGROUND: A well-constructed and properly operating influenza surveillance scheme is essential for public health. This study was conducted to evaluate the distribution of respiratory viruses in patients with influenza-like illness (ILI) through the first teaching hospital-based surveillance scheme for ILI in South Korea. METHODS: Respiratory specimens were obtained from adult patients (≥18 years) who visited the emergency department (ED) with ILI from week 40, 2011 to week 22, 2012. Multiplex PCR was performed to detect respiratory viruses: influenza virus, adenovirus, coronavirus, respiratory syncytial virus, rhinovirus, human metapneumovirus, parainfluenza virus, bocavirus, and enterovirus. RESULTS: Among 1,983 patients who visited the ED with ILI, 811 (40.9%) were male. The median age of patients was 43 years. Influenza vaccination rate was 21.7% (430/1,983) during the 2011–2012 season. At least one comorbidity was found in 18% of patients. The positive rate of respiratory viruses was 52.1% (1,033/1,983) and the total number of detected viruses was 1,100. Influenza A virus was the dominant agent (677, 61.5%) in all age groups. The prevalence of human metapneumovirus was higher in patients more than 50 years old, while adenovirus was detected only in younger adults. In 58 (5.6%) cases, two or more respiratory viruses were detected. The co-incidence case was identified more frequently in patients with hematologic malignancy or organ transplantation recipients, however it was not related to clinical outcomes. CONCLUSION: This study is valuable as the first extensive laboratory surveillance of the epidemiology of respiratory viruses in ILI patients through a teaching hospital-based influenza surveillance system in South Korea.",2013 May 22,"['Noh, Ji Yun', 'Song, Joon Young', 'Cheong, Hee Jin', 'Choi, Won Suk', 'Lee, Jacob', 'Lee, Jin-Soo', 'Wie, Seong-Heon', 'Jeong, Hye Won', 'Kim, Young Keun', 'Choi, Sung Hyuk', 'Han, Seung Baik', 'So, Byung-Hak', 'Kim, Hyun', 'Kim, Woo Joo']",PLoS One,,,True
71b9d32718c8ba343468da22dc28314f84b852ec,PMC,A Lattice Model for Influenza Spreading,http://dx.doi.org/10.1371/journal.pone.0063935,PMC3661600,23717512,CC BY,"We construct a stochastic SIR model for influenza spreading on a D-dimensional lattice, which represents the dynamic contact network of individuals. An age distributed population is placed on the lattice and moves on it. The displacement from a site to a nearest neighbor empty site, allows individuals to change the number and identities of their contacts. The dynamics on the lattice is governed by an attractive interaction between individuals belonging to the same age-class. The parameters, which regulate the pattern dynamics, are fixed fitting the data on the age-dependent daily contact numbers, furnished by the Polymod survey. A simple SIR transmission model with a nearest neighbors interaction and some very basic adaptive mobility restrictions complete the model. The model is validated against the age-distributed Italian epidemiological data for the influenza A(H1N1) during the [Image: see text] season, with sensible predictions for the epidemiological parameters. For an appropriate topology of the lattice, we find that, whenever the accordance between the contact patterns of the model and the Polymod data is satisfactory, there is a good agreement between the numerical and the experimental epidemiological data. This result shows how rich is the information encoded in the average contact patterns of individuals, with respect to the analysis of the epidemic spreading of an infectious disease.",2013 May 22,"['Liccardo, Antonella', 'Fierro, Annalisa']",PLoS One,,,True
c82205e91bbd1135020b4fdf0d9df2654c66650a,PMC,Global Organization of a Positive-strand RNA Virus Genome,http://dx.doi.org/10.1371/journal.ppat.1003363,PMC3662671,23717202,CC BY,"The genomes of plus-strand RNA viruses contain many regulatory sequences and structures that direct different viral processes. The traditional view of these RNA elements are as local structures present in non-coding regions. However, this view is changing due to the discovery of regulatory elements in coding regions and functional long-range intra-genomic base pairing interactions. The ∼4.8 kb long RNA genome of the tombusvirus tomato bushy stunt virus (TBSV) contains these types of structural features, including six different functional long-distance interactions. We hypothesized that to achieve these multiple interactions this viral genome must utilize a large-scale organizational strategy and, accordingly, we sought to assess the global conformation of the entire TBSV genome. Atomic force micrographs of the genome indicated a mostly condensed structure composed of interconnected protrusions extending from a central hub. This configuration was consistent with the genomic secondary structure model generated using high-throughput selective 2′-hydroxyl acylation analysed by primer extension (i.e. SHAPE), which predicted different sized RNA domains originating from a central region. Known RNA elements were identified in both domain and inter-domain regions, and novel structural features were predicted and functionally confirmed. Interestingly, only two of the six long-range interactions known to form were present in the structural model. However, for those interactions that did not form, complementary partner sequences were positioned relatively close to each other in the structure, suggesting that the secondary structure level of viral genome structure could provide a basic scaffold for the formation of different long-range interactions. The higher-order structural model for the TBSV RNA genome provides a snapshot of the complex framework that allows multiple functional components to operate in concert within a confined context.",2013 May 23,"['Wu, Baodong', 'Grigull, Jörg', 'Ore, Moriam O.', 'Morin, Sylvie', 'White, K. Andrew']",PLoS Pathog,,,True
054e3e247ad11de2be71be7215e30a44222271ab,PMC,Transient Oligomerization of the SARS-CoV N Protein – Implication for Virus Ribonucleoprotein Packaging,http://dx.doi.org/10.1371/journal.pone.0065045,PMC3662775,23717688,CC BY,"The nucleocapsid (N) phosphoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV) packages the viral genome into a helical ribonucleocapsid and plays a fundamental role during viral self-assembly. The N protein consists of two structural domains interspersed between intrinsically disordered regions and dimerizes through the C-terminal structural domain (CTD). A key activity of the protein is the ability to oligomerize during capsid formation by utilizing the dimer as a building block, but the structural and mechanistic bases of this activity are not well understood. By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that CTD acts as a primary transient oligomerization domain in solution. The data is consistent with the helical oligomer packing model of N protein observed in crystal. A systematic study of the oligomerization behavior revealed that altering the intermolecular electrostatic repulsion through changes in solution salt concentration or phosphorylation-mimicking mutations affects oligomerization propensity. We propose a biophysical mechanism where electrostatic repulsion acts as a switch to regulate N protein oligomerization.",2013 May 23,"['Chang, Chung-ke', 'Chen, Chia-Min Michael', 'Chiang, Ming-hui', 'Hsu, Yen-lan', 'Huang, Tai-huang']",PLoS One,,,True
4ab3c0ea7ec522f4fd4e3a2d92a975d3a054ca88,PMC,Transient Oligomerization of the SARS-CoV N Protein – Implication for Virus Ribonucleoprotein Packaging,http://dx.doi.org/10.1371/journal.pone.0065045,PMC3662775,23717688,CC BY,"The nucleocapsid (N) phosphoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV) packages the viral genome into a helical ribonucleocapsid and plays a fundamental role during viral self-assembly. The N protein consists of two structural domains interspersed between intrinsically disordered regions and dimerizes through the C-terminal structural domain (CTD). A key activity of the protein is the ability to oligomerize during capsid formation by utilizing the dimer as a building block, but the structural and mechanistic bases of this activity are not well understood. By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that CTD acts as a primary transient oligomerization domain in solution. The data is consistent with the helical oligomer packing model of N protein observed in crystal. A systematic study of the oligomerization behavior revealed that altering the intermolecular electrostatic repulsion through changes in solution salt concentration or phosphorylation-mimicking mutations affects oligomerization propensity. We propose a biophysical mechanism where electrostatic repulsion acts as a switch to regulate N protein oligomerization.",2013 May 23,"['Chang, Chung-ke', 'Chen, Chia-Min Michael', 'Chiang, Ming-hui', 'Hsu, Yen-lan', 'Huang, Tai-huang']",PLoS One,,,False
0d5be5a4268da7c08b478ca36721d46bd67bbe69,PMC,Effect of avian influenza A H5N1 infection on the expression of microRNA-141 in human respiratory epithelial cells,http://dx.doi.org/10.1186/1471-2180-13-104,PMC3663648,23663545,CC BY,"BACKGROUND: Avian influenza remains a serious threat to human health. The consequence of human infection varies markedly among different subtypes of avian influenza viruses. In addition to viral factors, the difference in host cellular response is likely to play a critical role. This study aims at elucidating how avian influenza infection perturbs the host’s miRNA regulatory pathways that may lead to adverse pathological events, such as cytokine storm, using the miRNA microarray approach. RESULTS: The results showed that dysregulation of miRNA expression was mainly observed in highly pathogenic avian influenza A H5N1 infection. We found that miR-21*, miR-100*, miR-141, miR-574-3p, miR-1274a and miR1274b were differentially expressed in response to influenza A virus infection. Interestingly, we demonstrated that miR-141, which was more highly induced by H5N1 than by H1N1 (p < 0.05), had an ability to suppress the expression of a cytokine - transforming growth factor (TGF)-β2. This was supported by the observation that the inhibitory effect could be reversed by antagomiR-141. CONCLUSIONS: Since TGF-β2 is an important cytokine that can act as both an immunosuppressive agent and a potent proinflammatory molecule through its ability to attract and regulate inflammatory molecules, and previous report showed that only seasonal influenza H1N1 (but not the other avian influenza subtypes) could induce a persistent expression of TGF-β2, we speculate that the modulation of TGF-β2 expression by different influenza subtypes via miR-141 might be a critical step for determining the outcome of either normal or excessive inflammation progression.",2013 May 10,"['Lam, Wai-Yip', 'Yeung, Apple Chung-Man', 'Ngai, Karry Lei-Ka', 'Li, Man-Shan', 'To, Ka-Fai', 'Tsui, Stephen Kwok-Wing', 'Chan, Paul Kay-Sheung']",BMC Microbiol,,,True
5e0504a1c581c36bbf2c2c97439b87b9834b108b,PMC,Induction of Interferon-Stimulated Genes on the IL-4 Response Axis by Epstein-Barr Virus Infected Human B Cells; Relevance to Cellular Transformation,http://dx.doi.org/10.1371/journal.pone.0064868,PMC3664578,23724103,CC BY,"Epstein-Barr virus (EBV) is an oncogenic virus that is associated with the pathogenesis of several human lymphoid malignancies, including Hodgkin's lymphoma. Infection of normal resting B cells with EBV results in activation to lymphoblasts that are phenotypically similar to those generated by physiological stimulation with CD40L plus IL-4. One important difference is that infection leads to the establishment of permanently growing lymphoblastoid cell lines, whereas CD40L/IL-4 blasts have finite proliferation lifespans. To identify early events which might later determine why EBV infected blasts go on to establish transformed cell lines, we performed global transcriptome analyses on resting B cells and on EBV and CD40L/IL-4 blasts after 7 days culture. As anticipated there was considerable overlap in the transcriptomes of the two types of lymphoblasts when compared to the original resting B cells, reflecting common changes associated with lymphocyte activation and proliferation. Of interest to us was a subset of 255 genes that were differentially expressed between EBV and CD40L/IL-4 blasts. Genes which were more highly expressed in EBV blasts were substantially and significantly enriched for a set of interferon-stimulated genes which on further in silico analyses were found to be repressed by IL-4 in other cell contexts and to be up-regulated in micro-dissected malignant cells from Hodgkin's lymphoma biopsies when compared to their normal germinal center cell counterparts. We hypothesized that EBV and IL-4 were targeting and discordantly regulating a common set of genes. This was supported experimentally in our B cell model where IL-4 stimulation partially reversed transcriptional changes which follow EBV infection and it impaired the efficiency of EBV-induced B cell transformation. Taken together, these data suggest that the discordant regulation of interferon and IL-4 pathway genes by EBV that occurs early following infection of B cells has relevance to the development or maintenance of an EBV-associated malignancy.",2013 May 27,"['Smith, Nikki', 'Tierney, Rosemary', 'Wei, Wenbin', 'Vockerodt, Martina', 'Murray, Paul G.', 'Woodman, Ciaran B.', 'Rowe, Martin']",PLoS One,,,True
dca48fcd1b8a28f470494d64ea3811707e28766b,PMC,Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein,http://dx.doi.org/10.1371/journal.pbio.1001571,PMC3665890,23723737,CC BY,"Transferrin Receptor (TfR1) is the cell-surface receptor that regulates iron uptake into cells, a process that is fundamental to life. However, TfR1 also facilitates the cellular entry of multiple mammalian viruses. We use evolutionary and functional analyses of TfR1 in the rodent clade, where two families of viruses bind this receptor, to mechanistically dissect how essential housekeeping genes like TFR1 successfully balance the opposing selective pressures exerted by host and virus. We find that while the sequence of rodent TfR1 is generally conserved, a small set of TfR1 residue positions has evolved rapidly over the speciation of rodents. Remarkably, all of these residues correspond to the two virus binding surfaces of TfR1. We show that naturally occurring mutations at these positions block virus entry while simultaneously preserving iron-uptake functionalities, both in rodent and human TfR1. Thus, by constantly replacing the amino acids encoded at just a few residue positions, TFR1 divorces adaptation to ever-changing viruses from preservation of key cellular functions. These dynamics have driven genetic divergence at the TFR1 locus that now enforces species-specific barriers to virus transmission, limiting both the cross-species and zoonotic transmission of these viruses.",2013 May 28,"['Demogines, Ann', 'Abraham, Jonathan', 'Choe, Hyeryun', 'Farzan, Michael', 'Sawyer, Sara L.']",PLoS Biol,,,True
1919d046fbf9c2b918e861d3c456876d110d5efb,PMC,Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein,http://dx.doi.org/10.1371/journal.pbio.1001571,PMC3665890,23723737,CC BY,"Transferrin Receptor (TfR1) is the cell-surface receptor that regulates iron uptake into cells, a process that is fundamental to life. However, TfR1 also facilitates the cellular entry of multiple mammalian viruses. We use evolutionary and functional analyses of TfR1 in the rodent clade, where two families of viruses bind this receptor, to mechanistically dissect how essential housekeeping genes like TFR1 successfully balance the opposing selective pressures exerted by host and virus. We find that while the sequence of rodent TfR1 is generally conserved, a small set of TfR1 residue positions has evolved rapidly over the speciation of rodents. Remarkably, all of these residues correspond to the two virus binding surfaces of TfR1. We show that naturally occurring mutations at these positions block virus entry while simultaneously preserving iron-uptake functionalities, both in rodent and human TfR1. Thus, by constantly replacing the amino acids encoded at just a few residue positions, TFR1 divorces adaptation to ever-changing viruses from preservation of key cellular functions. These dynamics have driven genetic divergence at the TFR1 locus that now enforces species-specific barriers to virus transmission, limiting both the cross-species and zoonotic transmission of these viruses.",2013 May 28,"['Demogines, Ann', 'Abraham, Jonathan', 'Choe, Hyeryun', 'Farzan, Michael', 'Sawyer, Sara L.']",PLoS Biol,,,False
4c0660d807475373cd5e4bf4ba268a1005b87712,PMC,Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein,http://dx.doi.org/10.1371/journal.pbio.1001571,PMC3665890,23723737,CC BY,"Transferrin Receptor (TfR1) is the cell-surface receptor that regulates iron uptake into cells, a process that is fundamental to life. However, TfR1 also facilitates the cellular entry of multiple mammalian viruses. We use evolutionary and functional analyses of TfR1 in the rodent clade, where two families of viruses bind this receptor, to mechanistically dissect how essential housekeeping genes like TFR1 successfully balance the opposing selective pressures exerted by host and virus. We find that while the sequence of rodent TfR1 is generally conserved, a small set of TfR1 residue positions has evolved rapidly over the speciation of rodents. Remarkably, all of these residues correspond to the two virus binding surfaces of TfR1. We show that naturally occurring mutations at these positions block virus entry while simultaneously preserving iron-uptake functionalities, both in rodent and human TfR1. Thus, by constantly replacing the amino acids encoded at just a few residue positions, TFR1 divorces adaptation to ever-changing viruses from preservation of key cellular functions. These dynamics have driven genetic divergence at the TFR1 locus that now enforces species-specific barriers to virus transmission, limiting both the cross-species and zoonotic transmission of these viruses.",2013 May 28,"['Demogines, Ann', 'Abraham, Jonathan', 'Choe, Hyeryun', 'Farzan, Michael', 'Sawyer, Sara L.']",PLoS Biol,,,False
5bfb1815d1873f05bde8557c59d26b840c7de981,PMC,Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein,http://dx.doi.org/10.1371/journal.pbio.1001571,PMC3665890,23723737,CC BY,"Transferrin Receptor (TfR1) is the cell-surface receptor that regulates iron uptake into cells, a process that is fundamental to life. However, TfR1 also facilitates the cellular entry of multiple mammalian viruses. We use evolutionary and functional analyses of TfR1 in the rodent clade, where two families of viruses bind this receptor, to mechanistically dissect how essential housekeeping genes like TFR1 successfully balance the opposing selective pressures exerted by host and virus. We find that while the sequence of rodent TfR1 is generally conserved, a small set of TfR1 residue positions has evolved rapidly over the speciation of rodents. Remarkably, all of these residues correspond to the two virus binding surfaces of TfR1. We show that naturally occurring mutations at these positions block virus entry while simultaneously preserving iron-uptake functionalities, both in rodent and human TfR1. Thus, by constantly replacing the amino acids encoded at just a few residue positions, TFR1 divorces adaptation to ever-changing viruses from preservation of key cellular functions. These dynamics have driven genetic divergence at the TFR1 locus that now enforces species-specific barriers to virus transmission, limiting both the cross-species and zoonotic transmission of these viruses.",2013 May 28,"['Demogines, Ann', 'Abraham, Jonathan', 'Choe, Hyeryun', 'Farzan, Michael', 'Sawyer, Sara L.']",PLoS Biol,,,False
08ee65d70ad0dae18dd402eb531103c2dfbbeffb,PMC,Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein,http://dx.doi.org/10.1371/journal.pbio.1001571,PMC3665890,23723737,CC BY,"Transferrin Receptor (TfR1) is the cell-surface receptor that regulates iron uptake into cells, a process that is fundamental to life. However, TfR1 also facilitates the cellular entry of multiple mammalian viruses. We use evolutionary and functional analyses of TfR1 in the rodent clade, where two families of viruses bind this receptor, to mechanistically dissect how essential housekeeping genes like TFR1 successfully balance the opposing selective pressures exerted by host and virus. We find that while the sequence of rodent TfR1 is generally conserved, a small set of TfR1 residue positions has evolved rapidly over the speciation of rodents. Remarkably, all of these residues correspond to the two virus binding surfaces of TfR1. We show that naturally occurring mutations at these positions block virus entry while simultaneously preserving iron-uptake functionalities, both in rodent and human TfR1. Thus, by constantly replacing the amino acids encoded at just a few residue positions, TFR1 divorces adaptation to ever-changing viruses from preservation of key cellular functions. These dynamics have driven genetic divergence at the TFR1 locus that now enforces species-specific barriers to virus transmission, limiting both the cross-species and zoonotic transmission of these viruses.",2013 May 28,"['Demogines, Ann', 'Abraham, Jonathan', 'Choe, Hyeryun', 'Farzan, Michael', 'Sawyer, Sara L.']",PLoS Biol,,,True
3b124808cb49c3530b23b6fda834fcbbc8af1988,PMC,"Trends in parameterization, economics and host behaviour in influenza pandemic modelling: a review and reporting protocol",http://dx.doi.org/10.1186/1742-7622-10-3,PMC3666982,23651557,CC BY,"BACKGROUND: The volume of influenza pandemic modelling studies has increased dramatically in the last decade. Many models incorporate now sophisticated parameterization and validation techniques, economic analyses and the behaviour of individuals. METHODS: We reviewed trends in these aspects in models for influenza pandemic preparedness that aimed to generate policy insights for epidemic management and were published from 2000 to September 2011, i.e. before and after the 2009 pandemic. RESULTS: We find that many influenza pandemics models rely on parameters from previous modelling studies, models are rarely validated using observed data and are seldom applied to low-income countries. Mechanisms for international data sharing would be necessary to facilitate a wider adoption of model validation. The variety of modelling decisions makes it difficult to compare and evaluate models systematically. CONCLUSIONS: We propose a model Characteristics, Construction, Parameterization and Validation aspects protocol (CCPV protocol) to contribute to the systematisation of the reporting of models with an emphasis on the incorporation of economic aspects and host behaviour. Model reporting, as already exists in many other fields of modelling, would increase confidence in model results, and transparency in their assessment and comparison.",2013 May 7,"['Carrasco, Luis R', 'Jit, Mark', 'Chen, Mark I', 'Lee, Vernon J', 'Milne, George J', 'Cook, Alex R']",Emerg Themes Epidemiol,,,True
8deca5b29c3d3c0b11f1c9032a981f95dc8d1619,PMC,Rapid Identification of Novel Immunodominant Proteins and Characterization of a Specific Linear Epitope of Campylobacter jejuni,http://dx.doi.org/10.1371/journal.pone.0065837,PMC3667084,23734261,CC BY,"Campylobacter jejuni remains one of the major gut pathogens of our time. Its zoonotic nature and wide-spread distribution in industrialized countries calls for a quick and reliable diagnostic tool. Antibody-based detection presents a suitable means to identify pathogenic bacteria. However, the knowledge about immunodominant targets is limited. Thus, an approach is presented, which allows for the rapid screening of numerous cDNA derived expression clones to identify novel antigens. The deeper understanding of immunodominant proteins assists in the design of diagnostic tools and furthers the insight into the bacterium’s pathogenicity as well as revealing potential candidates for vaccination. We have successfully screened 1536 clones of an expression library to identify 22 proteins that have not been described as immunodominant before. After subcloning the corresponding 22 genes and expression of full-length proteins, we investigated the immunodominant character by microarrays and ELISA. Subsequently, seven proteins were selected for epitope mapping. For cj0669 and cj0920c linear epitopes were identified. For cj0669, specificity assays revealed a specific linear epitope site. Consequently, an eleven amino acid residue sequence TLIKELKRLGI was analyzed via alanine scan, which revealed the glycine residue to be significant for binding of the antibody. The innovative approach presented herein of generating cDNAs of prokaryotes in combination with a microarray platform rendering time-consuming purification steps obsolete has helped to illuminate novel immunodominant proteins of C.jejuni. The findings of a specific linear epitope pave the way for a plethora of future research and the potential use in diagnostic applications such as serological screenings. Moreover, the current approach is easily adaptable to other highly relevant bacteria making it a formidable tool for the future discovery of antigens and potential biomarkers. Consequently, it is desirable to simplify the identification of structural epitopes, as this would extend the spectrum of novel epitopes to be detected.",2013 May 29,"['Hoppe, Sebastian', 'Bier, Frank F.', 'Nickisch-Rosenegk, Markus v.']",PLoS One,,,True
c5538a16c6ce27086250165a3d4ca7cbcbc3a127,PMC,Rapid Identification of Novel Immunodominant Proteins and Characterization of a Specific Linear Epitope of Campylobacter jejuni,http://dx.doi.org/10.1371/journal.pone.0065837,PMC3667084,23734261,CC BY,"Campylobacter jejuni remains one of the major gut pathogens of our time. Its zoonotic nature and wide-spread distribution in industrialized countries calls for a quick and reliable diagnostic tool. Antibody-based detection presents a suitable means to identify pathogenic bacteria. However, the knowledge about immunodominant targets is limited. Thus, an approach is presented, which allows for the rapid screening of numerous cDNA derived expression clones to identify novel antigens. The deeper understanding of immunodominant proteins assists in the design of diagnostic tools and furthers the insight into the bacterium’s pathogenicity as well as revealing potential candidates for vaccination. We have successfully screened 1536 clones of an expression library to identify 22 proteins that have not been described as immunodominant before. After subcloning the corresponding 22 genes and expression of full-length proteins, we investigated the immunodominant character by microarrays and ELISA. Subsequently, seven proteins were selected for epitope mapping. For cj0669 and cj0920c linear epitopes were identified. For cj0669, specificity assays revealed a specific linear epitope site. Consequently, an eleven amino acid residue sequence TLIKELKRLGI was analyzed via alanine scan, which revealed the glycine residue to be significant for binding of the antibody. The innovative approach presented herein of generating cDNAs of prokaryotes in combination with a microarray platform rendering time-consuming purification steps obsolete has helped to illuminate novel immunodominant proteins of C.jejuni. The findings of a specific linear epitope pave the way for a plethora of future research and the potential use in diagnostic applications such as serological screenings. Moreover, the current approach is easily adaptable to other highly relevant bacteria making it a formidable tool for the future discovery of antigens and potential biomarkers. Consequently, it is desirable to simplify the identification of structural epitopes, as this would extend the spectrum of novel epitopes to be detected.",2013 May 29,"['Hoppe, Sebastian', 'Bier, Frank F.', 'Nickisch-Rosenegk, Markus v.']",PLoS One,,,False
c0fd72cb00a30cf46c553708c2152cd09fc9f674,PMC,Metagenomic study of the viruses of African straw-coloured fruit bats: Detection of a chiropteran poxvirus and isolation of a novel adenovirus,http://dx.doi.org/10.1016/j.virol.2013.03.014,PMC3667569,23562481,CC BY,"Viral emergence as a result of zoonotic transmission constitutes a continuous public health threat. Emerging viruses such as SARS coronavirus, hantaviruses and henipaviruses have wildlife reservoirs. Characterising the viruses of candidate reservoir species in geographical hot spots for viral emergence is a sensible approach to develop tools to predict, prevent, or contain emergence events. Here, we explore the viruses of Eidolon helvum, an Old World fruit bat species widely distributed in Africa that lives in close proximity to humans. We identified a great abundance and diversity of novel herpes and papillomaviruses, described the isolation of a novel adenovirus, and detected, for the first time, sequences of a chiropteran poxvirus closely related with Molluscum contagiosum. In sum, E. helvum display a wide variety of mammalian viruses, some of them genetically similar to known human pathogens, highlighting the possibility of zoonotic transmission.",2013 Jul 5,"['Baker, Kate S.', 'Leggett, Richard M.', 'Bexfield, Nicholas H.', 'Alston, Mark', 'Daly, Gordon', 'Todd, Shawn', 'Tachedjian, Mary', 'Holmes, Clare E.G.', 'Crameri, Sandra', 'Wang, Lin-Fa', 'Heeney, Jonathan L.', 'Suu-Ire, Richard', 'Kellam, Paul', 'Cunningham, Andrew A.', 'Wood, James L.N.', 'Caccamo, Mario', 'Murcia, Pablo R.']",Virology,,,False
1acde2d851704500e78d9f3619528c43bbf3e2ba,PMC,Metagenomic study of the viruses of African straw-coloured fruit bats: Detection of a chiropteran poxvirus and isolation of a novel adenovirus,http://dx.doi.org/10.1016/j.virol.2013.03.014,PMC3667569,23562481,CC BY,"Viral emergence as a result of zoonotic transmission constitutes a continuous public health threat. Emerging viruses such as SARS coronavirus, hantaviruses and henipaviruses have wildlife reservoirs. Characterising the viruses of candidate reservoir species in geographical hot spots for viral emergence is a sensible approach to develop tools to predict, prevent, or contain emergence events. Here, we explore the viruses of Eidolon helvum, an Old World fruit bat species widely distributed in Africa that lives in close proximity to humans. We identified a great abundance and diversity of novel herpes and papillomaviruses, described the isolation of a novel adenovirus, and detected, for the first time, sequences of a chiropteran poxvirus closely related with Molluscum contagiosum. In sum, E. helvum display a wide variety of mammalian viruses, some of them genetically similar to known human pathogens, highlighting the possibility of zoonotic transmission.",2013 Jul 5,"['Baker, Kate S.', 'Leggett, Richard M.', 'Bexfield, Nicholas H.', 'Alston, Mark', 'Daly, Gordon', 'Todd, Shawn', 'Tachedjian, Mary', 'Holmes, Clare E.G.', 'Crameri, Sandra', 'Wang, Lin-Fa', 'Heeney, Jonathan L.', 'Suu-Ire, Richard', 'Kellam, Paul', 'Cunningham, Andrew A.', 'Wood, James L.N.', 'Caccamo, Mario', 'Murcia, Pablo R.']",Virology,,,False
8b112ca2f3995abd362486a677f883e402fc15da,PMC,Metagenomic study of the viruses of African straw-coloured fruit bats: Detection of a chiropteran poxvirus and isolation of a novel adenovirus,http://dx.doi.org/10.1016/j.virol.2013.03.014,PMC3667569,23562481,CC BY,"Viral emergence as a result of zoonotic transmission constitutes a continuous public health threat. Emerging viruses such as SARS coronavirus, hantaviruses and henipaviruses have wildlife reservoirs. Characterising the viruses of candidate reservoir species in geographical hot spots for viral emergence is a sensible approach to develop tools to predict, prevent, or contain emergence events. Here, we explore the viruses of Eidolon helvum, an Old World fruit bat species widely distributed in Africa that lives in close proximity to humans. We identified a great abundance and diversity of novel herpes and papillomaviruses, described the isolation of a novel adenovirus, and detected, for the first time, sequences of a chiropteran poxvirus closely related with Molluscum contagiosum. In sum, E. helvum display a wide variety of mammalian viruses, some of them genetically similar to known human pathogens, highlighting the possibility of zoonotic transmission.",2013 Jul 5,"['Baker, Kate S.', 'Leggett, Richard M.', 'Bexfield, Nicholas H.', 'Alston, Mark', 'Daly, Gordon', 'Todd, Shawn', 'Tachedjian, Mary', 'Holmes, Clare E.G.', 'Crameri, Sandra', 'Wang, Lin-Fa', 'Heeney, Jonathan L.', 'Suu-Ire, Richard', 'Kellam, Paul', 'Cunningham, Andrew A.', 'Wood, James L.N.', 'Caccamo, Mario', 'Murcia, Pablo R.']",Virology,,,False
59a34f8561b8a70870682450d318e81fc0820676,PMC,Antibody Quality and Protection from Lethal Ebola Virus Challenge in Nonhuman Primates Immunized with Rabies Virus Based Bivalent Vaccine,http://dx.doi.org/10.1371/journal.ppat.1003389,PMC3667758,23737747,CC0,"We have previously described the generation of a novel Ebola virus (EBOV) vaccine platform based on (a) replication-competent rabies virus (RABV), (b) replication-deficient RABV, or (c) chemically inactivated RABV expressing EBOV glycoprotein (GP). Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced antibodies against EBOV GP differ in their target, affinity, or the isotype. Our results show that IgG1-biased humoral responses as well as high levels of GP-specific antibodies were beneficial for the control of EBOV infection after immunization. These results further support the concept that a successful EBOV vaccine needs to induce strong antibodies against EBOV. We also showed that a dual vaccine against RABV and filoviruses is achievable; therefore addressing concerns for the marketability of this urgently needed vaccine.",2013 May 30,"['Blaney, Joseph E.', 'Marzi, Andrea', 'Willet, Mallory', 'Papaneri, Amy B.', 'Wirblich, Christoph', 'Feldmann, Friederike', 'Holbrook, Michael', 'Jahrling, Peter', 'Feldmann, Heinz', 'Schnell, Matthias J.']",PLoS Pathog,,,True
1297127819be12e7f5319edd0a9b35fd5cc566b7,PMC,An RNA Aptamer Provides a Novel Approach for the Induction of Apoptosis by Targeting the HPV16 E7 Oncoprotein,http://dx.doi.org/10.1371/journal.pone.0064781,PMC3667794,23738000,CC BY,"BACKGROUND: Human papillomavirus 16 (HPV16) is a high-risk DNA tumour virus, which is a major causative agent of cervical cancer. Cellular transformation is associated with deregulated expression of the E6 and E7 oncogenes. E7 has been shown to bind a number of cellular proteins, including the cell cycle control protein pRb. In this study, RNA aptamers (small, single-stranded oligonucleotides selected for high-affinity binding) to HPV16 E7 were employed as molecular tools to further investigate these protein-protein interactions. METHODOLOGY/PRINCIPAL FINDINGS: This study is focused on one aptamer (termed A2). Transfection of this molecule into HPV16-transformed cells resulted in inhibition of cell proliferation (shown using real-time cell electronic sensing and MTT assays) due to the induction of apoptosis (as demonstrated by Annexin V/propidium iodide staining). GST-pull down and bead binding assays were used to demonstrate that the binding of A2 required N-terminal residues of E7 known to be involved in interaction with the cell cycle control protein, pRb. Using a similar approach, A2 was shown to disrupt the interaction between E7 and pRb in vitro. Furthermore, transfection of HPV16-transformed cells with A2 appeared to result in the loss of E7 and rise in pRb levels, as observed by immunoblotting. CONCLUSIONS/SIGNIFICANCE: This paper includes the first characterisation of the effects of an E7 RNA aptamer in a cell line derived from a cervical carcinoma. Transfection of cells with A2 was correlated with the loss of E7 and the induction of apoptosis. Aptamers specific for a number of cellular and viral proteins have been documented previously; one aptamer (Macugen) is approved for clinical use and several others are in clinical trials. In addition to its role as a molecular tool, A2 could have further applications in the future.",2013 May 30,"['Nicol, Clare', 'Cesur, Özlem', 'Forrest, Sophie', 'Belyaeva, Tamara A.', 'Bunka, David H. J.', 'Blair, G. Eric', 'Stonehouse, Nicola J.']",PLoS One,,,True
20b5fc51aef8b077346c4587aad3811eebf8b11b,PMC,Monitoring Influenza Epidemics in China with Search Query from Baidu,http://dx.doi.org/10.1371/journal.pone.0064323,PMC3667820,23750192,CC BY,"Several approaches have been proposed for near real-time detection and prediction of the spread of influenza. These include search query data for influenza-related terms, which has been explored as a tool for augmenting traditional surveillance methods. In this paper, we present a method that uses Internet search query data from Baidu to model and monitor influenza activity in China. The objectives of the study are to present a comprehensive technique for: (i) keyword selection, (ii) keyword filtering, (iii) index composition and (iv) modeling and detection of influenza activity in China. Sequential time-series for the selected composite keyword index is significantly correlated with Chinese influenza case data. In addition, one-month ahead prediction of influenza cases for the first eight months of 2012 has a mean absolute percent error less than 11%. To our knowledge, this is the first study on the use of search query data from Baidu in conjunction with this approach for estimation of influenza activity in China.",2013 May 30,"['Yuan, Qingyu', 'Nsoesie, Elaine O.', 'Lv, Benfu', 'Peng, Geng', 'Chunara, Rumi', 'Brownstein, John S.']",PLoS One,,,True
574efe7771ff8495c4ace678a489b0a0869b0834,PMC,Pentraxin 3: An Immuno-Regulator in the Lungs,http://dx.doi.org/10.3389/fimmu.2013.00127,PMC3668324,23755050,CC BY,"Pentraxin 3 (PTX3) is a soluble pattern recognition receptor that is a humoral component of the innate immune system. It interacts with pathogenic moieties, infected and dying host cells and facilitates their removal through activation of appropriate innate and adaptive mechanisms. PTX3 is secreted by a diverse variety of cells, ranging from immune cells to structural cells, in response to Toll like receptor (TLR) engagement, inflammatory stimuli, and physical and chemical stress. Further, PTX3 plays an essential role in female fertility as it facilitates the organization of extracellular matrix in the cumulus oophorus. Such activity is also implicated in post-inflammation tissue repair. PTX3 is a multifunctional protein and plays a non-redundant role in providing immunity against potential immunological dangers. Thus, we assessed its role in lung immunity, as lungs are at a constant risk of infections and tissue damage that is attributable to perpetual exposure to foreign agents.",2013 May 31,"['Balhara, Jyoti', 'Koussih, Latifa', 'Zhang, Jingbo', 'Gounni, Abdelilah Soussi']",Front Immunol,,,True
721f194d7cd4953a229e067f3e1b79ec2cf22aca,PMC,A Focused Ethnographic Study of Alberta Cattle Veterinarians’ Decision Making about Diagnostic Laboratory Submissions and Perceptions of Surveillance Programs,http://dx.doi.org/10.1371/journal.pone.0064811,PMC3669388,23741397,CC BY,"The animal and public health communities need to address the challenge posed by zoonotic emerging infectious diseases. To minimize the impacts of future events, animal disease surveillance will need to enable prompt event detection and response. Diagnostic laboratory-based surveillance systems targeting domestic animals depend in large part on private veterinarians to submit samples from cases to a laboratory. In contexts where pre-diagnostic laboratory surveillance systems have been implemented, this group of veterinarians is often asked to input data. This scenario holds true in Alberta where private cattle veterinarians have been asked to participate in the Alberta Veterinary Surveillance Network-Veterinary Practice Surveillance, a platform to which pre-diagnostic disease and non-disease case data are submitted. Consequently, understanding the factors that influence these veterinarians to submit cases to a laboratory and the complex of factors that affect their participation in surveillance programs is foundational to interpreting disease patterns reported by laboratories and engaging veterinarians in surveillance. A focused ethnographic study was conducted with ten cattle veterinarians in Alberta. Individual in-depth interviews with participants were recorded and transcribed to enable thematic analysis. Laboratory submissions were biased toward outbreaks of unknown cause, cases with unusual mortality rates, and issues with potential herd-level implications. Decreasing cattle value and government support for laboratory testing have contributed to fewer submissions over time. Participants were willing participants in surveillance, though government support and collaboration were necessary. Changes in the beef industry and veterinary profession, as well as cattle producers themselves, present both challenges and opportunities in surveillance.",2013 May 31,"['Sawford, Kate', 'Vollman, Ardene Robinson', 'Stephen, Craig']",PLoS One,,,True
09f32524e7d13409a47b77c3f7af60251df282f6,PMC,Investigation of soils affected by burnt hospital wastes in Nigeria using PIXE,http://dx.doi.org/10.1186/2193-1801-2-208,PMC3669510,23741646,CC BY,"Improper management of hospital waste has been reported to be responsible for several acute outbreaks like the severe acute respiratory syndrome (SARS). In spite of these challenges, hospital wastes are sometimes not properly handled in Nigeria. To date, there has not been an adequate study on the effect and fate of burnt hospital waste on agricultural soil. The effect of burnt hospital wastes on the agricultural soil was conducted on soils sampled around farm settlement near Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, South West Nigeria. PIXE technique was employed with a 1.7 MV 5SDH Tandem Pelletron accelerator available at Centre for Energy Research and Development O.A.U Ile-Ife, Nigeria. Eleven elements- Si, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Zr and Pb were detected and their concentrations and enrichment factors determined. The presence of Pb and Cl at the elevated concentrations range of (77.8 ± 3.5 - 279.6 ± 97.6 and 102.2 ± 37.4 -167.2±17.43) ppm respectively in this study, is of serious health concern because of the agricultural practices in the neighborhoods of the study sites. There is a need for proper handling of hospital and other related hazardous wastes because of the possibility of such posing serious environmental pollution problems.",2013 May 7,"['Ephraim P, Inyang', 'Ita, Akpan', 'Eusebius I, Obiajunwa']",Springerplus,,,True
0b180c5c5edf329811114548e19a708303e7c1c2,PMC,Double-Stranded RNA Attenuates the Barrier Function of Human Pulmonary Artery Endothelial Cells,http://dx.doi.org/10.1371/journal.pone.0063776,PMC3670875,23755110,CC BY,"Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells. Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated. We analyzed the effects of double stranded RNA on primary human pulmonary artery endothelial cells (hPAECs). The effect of natural and synthetic double-stranded RNA (dsRNA) on hPAECs was investigated using trans-endothelial electric resistance, molecule trafficking, calcium (Ca(2+)) homeostasis, gene expression and proliferation studies. Furthermore, the morphology and mechanical changes of the cells caused by synthetic dsRNA was followed by in-situ atomic force microscopy, by vascular-endothelial cadherin and F-actin staining. Our results indicated that exposure of hPAECs to synthetic dsRNA led to functional deficits. This was reflected by morphological and mechanical changes and an increase in the permeability of the endothelial monolayer. hPAECs treated with synthetic dsRNA accumulated in the G1 phase of the cell cycle. Additionally, the proliferation rate of the cells in the presence of synthetic dsRNA was significantly decreased. Furthermore, we found that natural and synthetic dsRNA modulated Ca(2+) signaling in hPAECs by inhibiting the sarco-endoplasmic Ca(2+)-ATPase (SERCA) which is involved in the regulation of the intracellular Ca(2+) homeostasis and thus cell growth. Even upon synthetic dsRNA stimulation silencing of SERCA3 preserved the endothelial monolayer integrity. Our data identify novel mechanisms by which dsRNA can disrupt endothelial barrier function and these may be relevant in inflammatory processes.",2013 Jun 3,"['Bálint, Zoltán', 'Zabini, Diana', 'Konya, Viktoria', 'Nagaraj, Chandran', 'Végh, Attila G.', 'Váró, György', 'Wilhelm, Imola', 'Fazakas, Csilla', 'Krizbai, István A.', 'Heinemann, Akos', 'Olschewski, Horst', 'Olschewski, Andrea']",PLoS One,,,True
2d91222fa8318aa7814fe7ad58b9d97c09eb6330,PMC,The antimalarial ferroquine: from bench to clinic,http://dx.doi.org/10.1051/parasite/2011183207,PMC3671469,21894260,CC BY,"Ferroquine (FQ, SSR97193) is currently the most advanced organometallic drug candidate and about to complete phase II clinical trials as a treatment for uncomplicated malaria. This ferrocenecontaining compound is active against both chloroquine-susceptible and chloroquine-resistant Plasmodium falciparum and P. vivax strains and/or isolates. This article focuses on the discovery of FQ, its antimalarial activity, the hypothesis of its mode of action, the current absence of resistance in vitro and recent clinical trials.",2011 Aug 15,"['Biot, C.', 'Nosten, F.', 'Fraisse, L.', 'Ter-Minassian, D.', 'Khalife, J.', 'Dive, D.']",Parasite,,,True
ce387fc60565255c55785be208ae0b6b8fbb2ed3,PMC,The Pomegranate: Effects on Bacteria and Viruses That Influence Human Health,http://dx.doi.org/10.1155/2013/606212,PMC3671682,23762148,CC BY,"Pomegranates have been known for hundreds of years for their multiple health benefits, including antimicrobial activity. The recent surge in multidrug-resistant bacteria and the possibility of widespread global virus pandemics necessitate the need for additional preventative and therapeutic options to conventional drugs. Research indicates that pomegranates and their extracts may serve as natural alternatives due to their potency against a wide range of bacterial and viral pathogens. Nearly every part of the pomegranate plant has been tested for antimicrobial activities, including the fruit juice, peel, arils, flowers, and bark. Many studies have utilized pomegranate peel with success. There are various phytochemical compounds in pomegranate that have demonstrated antimicrobial activity, but most of the studies have found that ellagic acid and larger hydrolyzable tannins, such as punicalagin, have the highest activities. In some cases the combination of the pomegranate constituents offers the most benefit. The positive clinical results on pomegranate and suppression of oral bacteria are intriguing and worthy of further study. Much of the evidence for pomegranates' antibacterial and antiviral activities against foodborne pathogens and other infectious disease organisms comes from in vitro cell-based assays, necessitating further confirmation of in vivo efficacy through human clinical trials.",2013 May 20,"['Howell, Amy B.', ""D'Souza, Doris H.""]",Evid Based Complement Alternat Med,,,True
af5ac6d8e177f588034d75237f65dc8d6c0deb2f,PMC,Impact of genotype 1 and 2 of porcine reproductive and respiratory syndrome viruses on interferon-α responses by plasmacytoid dendritic cells,http://dx.doi.org/10.1186/1297-9716-44-33,PMC3672080,23675981,CC BY,"Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) infections are characterized by prolonged viremia and viral shedding consistent with incomplete immunity. Type I interferons (IFN) are essential for mounting efficient antiviral innate and adaptive immune responses, but in a recent study, North American PRRSV genotype 2 isolates did not induce, or even strongly inhibited, IFN-α in plasmacytoid dendritic cells (pDC), representing “professional IFN-α-producing cells”. Since inhibition of IFN-α expression might initiate PRRSV pathogenesis, we further characterized PRRSV effects and host modifying factors on IFN-α responses of pDC. Surprisingly, a variety of type 1 and type 2 PRRSV directly stimulated IFN-α secretion by pDC. The effect did not require live virus and was mediated through the TLR7 pathway. Furthermore, both IFN-γ and IL-4 significantly enhanced the pDC production of IFN-α in response to PRRSV exposure. PRRSV inhibition of IFN-α responses from enriched pDC stimulated by CpG oligodeoxynucleotides was weak or absent. VR-2332, the prototype genotype 2 PRRSV, only suppressed the responses by 34%, and the highest level of suppression (51%) was induced by a Chinese highly pathogenic PRRSV isolate. Taken together, these findings demonstrate that pDC respond to PRRSV and suggest that suppressive activities on pDC, if any, are moderate and strain-dependent. Thus, pDC may be a source of systemic IFN-α responses reported in PRRSV-infected animals, further contributing to the puzzling immunopathogenesis of PRRS.",2013 May 15,"['Baumann, Arnaud', 'Mateu, Enric', 'Murtaugh, Michael P', 'Summerfield, Artur']",Vet Res,,,True
70b6d8307a4bba54b599dc35cec46f521fe6f2ac,PMC,The JPC-SE Position Statement on Asbestos: A Long-Overdue Appeal by Epidemiologists to Ban Asbestos Worldwide and End Related Global Environmental Injustice,http://dx.doi.org/10.1289/ehp.1306892,PMC3673210,23635993,CC0,,2013 May 1,"Al-Delaimy, Wael K.",Environ Health Perspect,,,True
134da4eba94dc9b9f03a9244d62aee56abe0de56,PMC,A Novel Lactococcal Vaccine Expressing a Peptide from the M2 Antigen of H5N2 Highly Pathogenic Avian Influenza A Virus Prolongs Survival of Vaccinated Chickens,http://dx.doi.org/10.1155/2013/316926,PMC3674685,23766929,CC BY,"A cost-effective and efficacious influenza vaccine for use in commercial poultry farms would help protect against avian influenza outbreaks. Current influenza vaccines for poultry are expensive and subtype specific, and therefore there is an urgent need to develop a universal avian influenza vaccine. We have constructed a live bacterial vaccine against avian influenza by expressing a conserved peptide from the ectodomain of M2 antigen (M2e) on the surface of Lactococcus lactis (LL). Chickens were vaccinated intranasally with the lactococcal vaccine (LL-M2e) or subcutaneously with keyhole-limpet-hemocyanin conjugated M2e (KLH-M2e). Vaccinated and nonvaccinated birds were challenged with high pathogenic avian influenza virus A subtype H5N2. Birds vaccinated with LL-M2e or KLH-M2e had median survival times of 5.5 and 6.0 days, respectively, which were significantly longer than non-vaccinated birds (3.5 days). Birds vaccinated subcutaneously with KLH-M2e had a lower mean viral burden than either of the other two groups. However, there was a significant correlation between the time of survival and M2e-specific serum IgG. The results of these trials show that birds in both vaccinated groups had significantly (P < 0.05) higher median survival times than non-vaccinated birds and that this protection could be due to M2e-specific serum IgG.",2013 May 22,"['Reese, Kaleb A.', 'Lupfer, Christopher', 'Johnson, Rudd C.', 'Mitev, Georgi M.', 'Mullen, Valerie M.', 'Geller, Bruce L.', 'Pastey, Manoj']",Vet Med Int,,,True
4572a8588d9d97cf1aa46241f2cf9e4a4d52dab8,PMC,Nanorobot Hardware Architecture for Medical Defense,http://dx.doi.org/10.3390/s8052932,PMC3675524,27879858,CC BY,"This work presents a new approach with details on the integrated platform and hardware architecture for nanorobots application in epidemic control, which should enable real time in vivo prognosis of biohazard infection. The recent developments in the field of nanoelectronics, with transducers progressively shrinking down to smaller sizes through nanotechnology and carbon nanotubes, are expected to result in innovative biomedical instrumentation possibilities, with new therapies and efficient diagnosis methodologies. The use of integrated systems, smart biosensors, and programmable nanodevices are advancing nanoelectronics, enabling the progressive research and development of molecular machines. It should provide high precision pervasive biomedical monitoring with real time data transmission. The use of nanobioelectronics as embedded systems is the natural pathway towards manufacturing methodology to achieve nanorobot applications out of laboratories sooner as possible. To demonstrate the practical application of medical nanorobotics, a 3D simulation based on clinical data addresses how to integrate communication with nanorobots using RFID, mobile phones, and satellites, applied to long distance ubiquitous surveillance and health monitoring for troops in conflict zones. Therefore, the current model can also be used to prevent and save a population against the case of some targeted epidemic disease.",2008 May 6,"['Cavalcanti, Adriano', 'Shirinzadeh, Bijan', 'Zhang, Mingjun', 'Kretly, Luiz C.']",Sensors (Basel),,,True
955cb107f58aff48a58de2473c2fe04e42bfa1e3,PMC,Self-Oligomerization Is Essential for Enhanced Immunological Activities of Soluble Recombinant Calreticulin,http://dx.doi.org/10.1371/journal.pone.0064951,PMC3677884,23762269,CC BY,"We have recently reported that calreticulin (CRT), a luminal resident protein, can be found in the sera of patients with rheumatoid arthritis and also that recombinant CRT (rCRT) exhibits extraordinarily strong immunological activities. We herein further demonstrate that rCRT fragments 18–412 (rCRT/18-412), rCRT/39-272, rCRT/120-308 and rCRT/120-250 can self-oligomerize in solution and are 50–100 fold more potent than native CRT (nCRT, isolated from mouse livers) in activating macrophages in vitro. We narrowed down the active site of CRT to residues 150–230, the activity of which also depends on dimerization. By contrast, rCRT/18-197 is almost completely inactive. When rCRT/18-412 is fractionated into oligomers and monomers by gel filtration, the oligomers maintain most of their immunological activities in terms of activating macrophages in vitro and inducing specific antibodies in vivo, while the monomers were much less active by comparison. Additionally, rCRT/18-412 oligomers are much better than monomers in binding to, and uptake by, macrophages. Inhibition of macrophage endocytosis partially blocks the stimulatory effect of rCRT/18-412. We conclude that the immunologically active site of CRT maps between residues 198–230 and that soluble CRT could acquire potent immuno-pathological activities in microenvironments favoring its oligomerization.",2013 Jun 10,"['Huang, Shang-Hui', 'Zhao, Li-Xiang', 'Hong, Chao', 'Duo, Cui-Cui', 'Guo, Bing-Nan', 'Zhang, Li-Juan', 'Gong, Zheng', 'Xiong, Si-Dong', 'Gong, Fang-Yuan', 'Gao, Xiao-Ming']",PLoS One,,,True
05513568bb7b58bb7df33023160838ac885a6144,PMC,Coalescent inference for infectious disease: meta-analysis of hepatitis C,http://dx.doi.org/10.1098/rstb.2012.0314,PMC3678333,23382432,CC BY,"Genetic analysis of pathogen genomes is a powerful approach to investigating the population dynamics and epidemic history of infectious diseases. However, the theoretical underpinnings of the most widely used, coalescent methods have been questioned, casting doubt on their interpretation. The aim of this study is to develop robust population genetic inference for compartmental models in epidemiology. Using a general approach based on the theory of metapopulations, we derive coalescent models under susceptible–infectious (SI), susceptible–infectious–susceptible (SIS) and susceptible–infectious–recovered (SIR) dynamics. We show that exponential and logistic growth models are equivalent to SI and SIS models, respectively, when co-infection is negligible. Implementing SI, SIS and SIR models in BEAST, we conduct a meta-analysis of hepatitis C epidemics, and show that we can directly estimate the basic reproductive number (R(0)) and prevalence under SIR dynamics. We find that differences in genetic diversity between epidemics can be explained by differences in underlying epidemiology (age of the epidemic and local population density) and viral subtype. Model comparison reveals SIR dynamics in three globally restricted epidemics, but most are better fit by the simpler SI dynamics. In summary, metapopulation models provide a general and practical framework for integrating epidemiology and population genetics for the purposes of joint inference.",2013 Mar 19,"['Dearlove, Bethany', 'Wilson, Daniel J.']",Philos Trans R Soc Lond B Biol Sci,,,True
808eb805948a72da00d370c274656653679536b5,PMC,"Epitope Mapping of M36, a Human Antibody Domain with Potent and Broad HIV-1 Inhibitory Activity",http://dx.doi.org/10.1371/journal.pone.0066638,PMC3679054,23776690,CC BY,"M36 is the first member of a novel class of potent HIV-1 entry inhibitors based on human engineered antibody domains (eAds). It exhibits broad inhibitory activity suggesting that its CD4-induced epitope is highly conserved. Here, we describe fine mapping of its epitope by using several approaches. First, a panel of mimotopes was affinity-selected from a random peptide library and potential m36-binding residues were computationally predicted. Second, homology modeling of m36 and molecular docking of m36 onto gp120 revealed potentially important residues in gp120-m36 interactions. Third, the predicted contact residues were verified by site-directed mutagenesis. Taken together, m36 epitope comprising three discontinuous sites including six key gp120 residues (Site C1: Thr123 and Pro124; Site C3: Glu370 and Ile371; Site C4: Met426 and Trp427) were identified. In the 3D structure of gp120, the sites C1 and C4 are located in the bridging sheet and the site C3 is within the β15-α3 excursion, which play essential roles for the receptor- and coreceptor-binding and are major targets of neutralizing antibodies. Based on these results we propose a precise localization of the m36 epitope and suggest a mechanism of its broad inhibitory activity which could help in the development of novel HIV-1 therapeutics based on eAds.",2013 Jun 11,"['Wan, Chao', 'Sun, Jianping', 'Chen, Weizao', 'Yuan, Xiaohui', 'Chong, Huihui', 'Prabakaran, Ponraj', 'Dimitrov, Dimiter S.', 'He, Yuxian']",PLoS One,,,True
e3de6d6d50592102725cbe2ee5cb0fe02b851aac,PMC,Inhibitory Effect of Resveratrol against Duck Enteritis Virus In Vitro,http://dx.doi.org/10.1371/journal.pone.0065213,PMC3679110,23776451,CC BY,"Duck viral enteritis (DVE) is an acute, contagious herpesvirus infection of ducks, geese, and swans of all ages and species. This disease has been responsible for significant economic losses in domestic and wild waterfowl as a result of mortality, and decreased egg production. Resveratrol is a naturally occurring phytoalexin in specific plants and exhibits inhibitory activity against many kinds of virus. In this paper, resveratrol was found to inhibit duck enteritis virus (DEV) replication in a dose-dependent manner, with a 50% inhibition concentration of 3.85 μg/mL. The inhibition in virus multiplication in the presence of resveratrol was not attributed to direct inactivation or inhibition of virus attachment to the host cells, but to the inhibition of viral multiplication in host cells. The assay of the time of addition limited the drug effect during the first 8 h of infection. This conclusion was supported by the ultrastructure images of the early stage of DEV infection, which showed that the replication of virus nucleic acid and the formation of the capsid in the cell nucleus were suppressed. In the indirect immunofluorescence assay, proteins expression in DEV infected duck embryo fibroblasts (DEFs) within 24 h post-infection (p.i.) was also effectively suppressed by resveratrol. In summary, the resveratrol has a good activity against DEV infection in vitro, which could be attributed to that fact that several essential immediate early viral proteins for virus replication were impacted by resveratrol.",2013 Jun 11,"['Xu, Jiao', 'Yin, Zhongqiong', 'Li, Li', 'Cheng, Anchun', 'Jia, Renyong', 'Song, Xu', 'Lu, Hongke', 'Dai, Shujun', 'Lv, Cheng', 'Liang, Xiaoxia', 'He, Changliang', 'Zhao, Ling', 'Su, Gang', 'Ye, Gang', 'Shi, Fei']",PLoS One,,,True
c9d84fcde35a82c200f779df24657558638bf40b,PMC,Fading vision: knowledge translation in the implementation of a public health policy intervention,http://dx.doi.org/10.1186/1748-5908-8-59,PMC3680003,23734672,CC BY,"BACKGROUND: In response to several high profile public health crises, public health renewal is underway in Canada. In the province of British Columbia, the Ministry of Health initiated a collaborative evidence-informed process involving a steering committee of representatives from the six health authorities. A Core Functions (CF) Framework was developed, identifying 21 core public health programs. For each core program, an evidence review was conducted and a model core program paper developed. These documents were distributed to health authorities to guide development of their own renewed public health services. The CF implementation was conceptualized as an embedded knowledge translation process. A CF coordinator in each health authority was to facilitate a gap analysis and development of a performance improvement plan for each core program, and post these publically on the health authority website. METHODS: Interviews (n = 19) and focus groups (n = 8) were conducted with a total of 56 managers and front line staff from five health authorities working in the Healthy Living and Sexually Transmitted Infection Prevention core programs. All interviews and focus groups were digitally recorded, transcribed and verified by the project coordinator. Five members of the research team used NVivo 9 to manage data and conducted a thematic analysis. RESULTS: Four main themes emerged concerning implementation of the CF Framework generally, and the two programs specifically. The themes were: ‘you’ve told me what, now tell me how’; ‘the double bind’; ‘but we already do that’; and the ‘selling game.’ Findings demonstrate the original vision of the CF process was lost in the implementation process and many participants were unaware of the CF framework or process. CONCLUSIONS: Results are discussed with respect to a well-known framework on the adoption, assimilation, and implementation of innovations in health services organizations. Despite attempts of the Ministry of Health and the Steering Committee to develop and implement a collaborative, evidence-informed policy intervention, there were several barriers to the realization of the vision for core public health functions implementation, at least in the early stages. In neglecting the implementation process, it seems unlikely that the expected benefits of the public health renewal process will be realized.",2013 Jun 4,"['Tomm-Bonde, Laura', 'Schreiber, Rita S', 'Allan, Diane E', 'MacDonald, Marjorie', 'Pauly, Bernie', 'Hancock, Trevor']",Implement Sci,,,True
dec25863e871c025ecfd92611e727196ae88cb5b,PMC,Introducing the Outbreak Threshold in Epidemiology,http://dx.doi.org/10.1371/journal.ppat.1003277,PMC3680036,23785276,CC BY,"When a pathogen is rare in a host population, there is a chance that it will die out because of stochastic effects instead of causing a major epidemic. Yet no criteria exist to determine when the pathogen increases to a risky level, from which it has a large chance of dying out, to when a major outbreak is almost certain. We introduce such an outbreak threshold (T(0)), and find that for large and homogeneous host populations, in which the pathogen has a reproductive ratio R(0), on the order of 1/Log(R(0)) infected individuals are needed to prevent stochastic fade-out during the early stages of an epidemic. We also show how this threshold scales with higher heterogeneity and R(0) in the host population. These results have implications for controlling emerging and re-emerging pathogens.",2013 Jun 6,"['Hartfield, Matthew', 'Alizon, Samuel']",PLoS Pathog,,,True
7ddadb59be0e7a80bfe88d3ff35c41d261c7a9b0,PMC,Introducing the Outbreak Threshold in Epidemiology,http://dx.doi.org/10.1371/journal.ppat.1003277,PMC3680036,23785276,CC BY,"When a pathogen is rare in a host population, there is a chance that it will die out because of stochastic effects instead of causing a major epidemic. Yet no criteria exist to determine when the pathogen increases to a risky level, from which it has a large chance of dying out, to when a major outbreak is almost certain. We introduce such an outbreak threshold (T(0)), and find that for large and homogeneous host populations, in which the pathogen has a reproductive ratio R(0), on the order of 1/Log(R(0)) infected individuals are needed to prevent stochastic fade-out during the early stages of an epidemic. We also show how this threshold scales with higher heterogeneity and R(0) in the host population. These results have implications for controlling emerging and re-emerging pathogens.",2013 Jun 6,"['Hartfield, Matthew', 'Alizon, Samuel']",PLoS Pathog,,,False
3498e7e96b742565d9041107cae12e667b394f9f,PMC,Transcription analysis of the porcine alveolar macrophage response to porcine circovirus type 2,http://dx.doi.org/10.1186/1471-2164-14-353,PMC3680065,23711280,CC BY,"BACKGROUND: Porcine circovirus type 2 (PCV2) is the causal agent of postweaning multisystemic wasting syndrome (PMWS), which has severely impacted the swine industry worldwide. PCV2 triggers a weak and atypical innate immune response, but the key genes and mechanisms by which the virus interferes with host innate immunity have not yet been elucidated. In this study, genes that control the response of primary porcine alveolar macrophages (PAMs), the main target of PCV2, were profiled in vitro. RESULTS: PAMs were successfully infected by PCV2-WH strain, as evidenced quantitative real-time polymerase chain reaction (qPCR) and immunofluorescence assay (IFA) results. Infection-related differential gene expression was investigated using pig microarrays from the US Pig Genome Coordination Program and validated by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Microarray analysis at 24 and 48 hours post-infection (HPI) revealed 266 and 175 unique genes, respectively, that were differentially expressed (false discovery rate <0.05; fold-change >2). Only six genes were differentially expressed between 24 and 48 HPI. The up-regulated genes were principally related to immune response, cytokine activity, locomotion, regulation of cell proliferation, apoptosis, cell growth arrest, and antigen procession and presentation. The down-regulated genes were mainly involved in terpenoid biosynthesis, carbohydrate metabolism, translation, proteasome degradation, signal transducer activity, and ribosomal proteins, which were representative of the reduced vital activity of PCV2-infected cells. CONCLUSIONS: PCV2 infection of PAMs causes up-regulation of genes related to inflammation, indicating that PCV2 may induce systematic inflammation. PCV2 persistently induced cytokines, mainly through the Toll-like receptor (TLR) 1 and TLR9 pathways, which may promote high levels of cytokine secretion. PCV2 may prevent apoptosis in PAMs by up-regulating SERPINB9 expression, possibly to lengthen the duration of PCV2 replication-permissive conditions. The observed gene expression profile may provide insights into the underlying immunological response and pathological changes that occur in pigs following PCV2 infection.",2013 May 27,"['Li, Wentao', 'Liu, Shuqing', 'Wang, Yang', 'Deng, Feng', 'Yan, Weidong', 'Yang, Kun', 'Chen, Huanchun', 'He, Qigai', 'Charreyre, Catherine', 'Audoneet, Jean-Christophe']",BMC Genomics,,,True
b6e8f6a447550c5a8d3581adfffb225e8b59fe43,PMC,Identification of canine parvovirus with the Q370R point mutation in the VP2 gene from a giant panda (Ailuropoda melanoleuca),http://dx.doi.org/10.1186/1743-422X-10-163,PMC3680276,23706032,CC BY,"BACKGROUND: In this study, we sequenced and phylogenetic analyses of the VP2 genes from twelve canine parvovirus (CPV) strains obtained from eleven domestic dogs and a giant panda (Ailuropoda melanoleuca) in China. A novel canine parvovirus (CPV) was detected from the giant panda in China. RESULTS: Nucleotide and phylogenetic analysis of the capsid protein VP2 gene classified the CPV as a new CPV-2a type. Substitution of Gln for Arg at the conserved 370 residue in CPV presents an unusual variation in the new CPV-2a amino acid sequence of the giant panda and is further evidence for the continuing evolution of the virus. CONCLUSIONS: These findings extend the knowledge on CPV molecular epidemiology of particular relevance to wild carnivores.",2013 May 26,"['Guo, Ling', 'Yang, Shao-lin', 'Chen, Shi-jie', 'Zhang, Zhihe', 'Wang, Chengdong', 'Hou, Rong', 'Ren, Yupeng', 'wen, Xintian', 'Cao, Sanjie', 'Guo, Wanzhu', 'Hao, Zhongxiang', 'Quan, Zifang', 'Zhang, Manli', 'Yan, Qi-gui']",Virol J,,,True
339f0cd12ca08506c22c8b62eb4b3283a437271a,PMC,Correlation between Dengue-Specific Neutralizing Antibodies and Serum Avidity in Primary and Secondary Dengue Virus 3 Natural Infections in Humans,http://dx.doi.org/10.1371/journal.pntd.0002274,PMC3681624,23785536,CC BY,"Although heterotypic secondary infection with dengue virus (DENV) is associated with severe disease, the majority of secondary infections are mild or asymptomatic. The mechanisms of antibody-mediated protection are poorly understood. In 2010, 108 DENV3-positive cases were enrolled in a pediatric hospital-based study in Managua, Nicaragua, with 61 primary and 47 secondary infections. We analyzed DENV-specific neutralization titers (NT(50)), IgM and IgG avidity, and antibody titer in serum samples collected during acute and convalescent phases and 3, 6, and 18 months post-infection. NT(50) titers peaked at convalescence and decreased thereafter. IgG avidity to DENV3 significantly increased between convalescent and 3-month time-points in primary DENV infections and between the acute and convalescent phase in secondary DENV infections. While avidity to DENV2, a likely previous infecting serotype, was initially higher than avidity to DENV3 in secondary DENV infections, the opposite relation was observed 3–18 months post-infection. We found significant correlations between IgM avidity and NT(50) in acute primary cases and between IgG avidity and NT(50) in secondary DENV infections. In summary, our findings indicate that IgM antibodies likely play a role in early control of DENV infections. IgG serum avidity to DENV, analyzed for the first time in longitudinal samples, switches from targeting mainly cross-reactive serotype(s) to the current infecting serotype over time. Finally, serum avidity correlates with neutralization capacity.",2013 Jun 13,"['Puschnik, Andreas', 'Lau, Louis', 'Cromwell, Elizabeth A.', 'Balmaseda, Angel', 'Zompi, Simona', 'Harris, Eva']",PLoS Negl Trop Dis,,,True
8b11ed8edd1f59ac713ddcc3282ad5a98b8b68b7,PMC,Efficient Sensing of Infected Cells in Absence of Virus Particles by Blasmacytoid Dendritic Cells Is Blocked by the Viral Ribonuclease E(rns),http://dx.doi.org/10.1371/journal.ppat.1003412,PMC3681750,23785283,CC BY,"Plasmacytoid dendritic cells (pDC) have been shown to efficiently sense HCV- or HIV-infected cells, using a virion-free pathway. Here, we demonstrate for classical swine fever virus, a member of the Flaviviridae, that this process is much more efficient in terms of interferon-alpha induction when compared to direct stimulation by virus particles. By employment of virus replicon particles or infectious RNA which can replicate but not form de novo virions, we exclude a transfer of virus from the donor cell to the pDC. pDC activation by infected cells was mediated by a contact-dependent RNA transfer to pDC, which was sensitive to a TLR7 inhibitor. This was inhibited by drugs affecting the cytoskeleton and membrane cholesterol. We further demonstrate that a unique viral protein with ribonuclease activity, the viral E(rns) protein of pestiviruses, efficiently prevented this process. This required intact ribonuclease function in intracellular compartments. We propose that this pathway of activation could be of particular importance for viruses which tend to be mostly cell-associated, cause persistent infection, and are non-cytopathogenic.",2013 Jun 13,"['Python, Sylvie', 'Gerber, Markus', 'Suter, Rolf', 'Ruggli, Nicolas', 'Summerfield, Artur']",PLoS Pathog,,,True
3bad4716622640d66aad1bf65067abc5b5a2cb01,PMC,"Different Immunity Elicited by Recombinant H5N1 Hemagglutinin Proteins Containing Pauci-Mannose, High-Mannose, or Complex Type N-Glycans",http://dx.doi.org/10.1371/journal.pone.0066719,PMC3682957,23799128,CC BY,"Highly pathogenic avian influenza H5N1 viruses can result in poultry and occasionally in human mortality. A safe and effective H5N1 vaccine is urgently needed to reduce the pandemic potential. Hemagglutinin (HA), a major envelope protein accounting for approximately 80% of spikes in influenza virus, is often used as a major antigen for subunit vaccine development. In this study, we conducted a systematic study of the immune response against influenza virus infection following immunization with recombinant HA proteins expressed in insect (Sf9) cells, insect cells that contain exogenous genes for elaborating N-linked glycans (Mimic) and mammalian cells (CHO). While the antibody titers are higher with the insect cell derived HA proteins, the neutralization and HA inhibition titers are much higher with the mammalian cell produced HA proteins. Recombinant HA proteins containing tri- or tetra-antennary complex, terminally sialylated and asialyated-galactose type N-glycans induced better protective immunity in mice to lethal challenge. The results are highly relevant to issues that should be considered in the production of fragment vaccines.",2013 Jun 14,"['Lin, Shih-Chang', 'Jan, Jia-Tsrong', 'Dionne, Ben', 'Butler, Michael', 'Huang, Ming-Hsi', 'Wu, Chung-Yi', 'Wong, Chi-Huey', 'Wu, Suh-Chin']",PLoS One,,,True
44676dd185a852b134c04a333d31b7e081f419f0,PMC,Sumoylation at the Host-Pathogen Interface,http://dx.doi.org/10.3390/biom2020203,PMC3685863,23795346,CC BY,"Many viral proteins have been shown to be sumoylated with corresponding regulatory effects on their protein function, indicating that this host cell modification process is widely exploited by viral pathogens to control viral activity. In addition to using sumoylation to regulate their own proteins, several viral pathogens have been shown to modulate overall host sumoylation levels. Given the large number of cellular targets for SUMO addition and the breadth of critical cellular processes that are regulated via sumoylation, viral modulation of overall sumoylation presumably alters the cellular environment to ensure that it is favorable for viral reproduction and/or persistence. Like some viruses, certain bacterial plant pathogens also target the sumoylation system, usually decreasing sumoylation to disrupt host anti-pathogen responses. The recent demonstration that Listeria monocytogenes also disrupts host sumoylation, and that this is required for efficient infection, extends the plant pathogen observations to a human pathogen and suggests that pathogen modulation of host sumoylation may be more widespread than previously appreciated. This review will focus on recent aspects of how pathogens modulate the host sumoylation system and how this benefits the pathogen.",2012 Apr 5,"Wilson, Van G.",Biomolecules,,,True
78330b92514605d59bb22b99c517538f83c2e2b7,PMC,Evaluation and molecular characterization of human adenovirus in drinking water supplies: viral integrity and viability assays,http://dx.doi.org/10.1186/1743-422X-10-166,PMC3686584,23714224,CC BY,"BACKGROUND: Human adenoviruses (HAdVs) are the second-leading cause of childhood gastroenteritis worldwide. This virus is commonly found in environmental waters and is very resistant to water disinfection and environmental stressors, especially UV light inactivation. Molecular techniques, such as PCR-based methods (Polymerase Chain Reaction), are commonly used to detect and identify viral contamination in water, although PCR alone does not allow the discrimination between infectious and non-infectious viral particles. A combination of cell culture and PCR has allowed detection of infectious viruses that grow slowly or fail to produce cytopathic effects (CPE) in cell culture. This study aimed to assess the integrity and viability of human adenovirus (HAdV) in environmental water and evaluate circulating strains by molecular characterization in three sites of the water supply in Florianópolis, Santa Catarina Island, Brazil: Peri Lagoon water, spring source water, and water from the public water supply system. METHODS: Water samples were collected, concentrated and HAdV quantified by real-time PCR. Viral integrity was evaluated by enzymatic assay (DNase I) and infectivity by plaque assay (PA) and integrated cell culture using transcribed mRNA (ICC-RT-qPCR). Samples containing particles of infectious HAdV were selected for sequencing and molecular characterization. RESULTS: The analyzed sites contained 83, 66 and 58% undamaged HAdV particles (defined as those in which the genetic material is protected by the viral capsid) at Peri Lagoon, spring source water and public supply system water, respectively. Of these, 66% of the particles (by PA) and 75% (by ICC-RT-qPCR) HAdV were shown to be infectious, due to being undamaged in Peri Lagoon, 33% (by PA) and 58% (by ICC-RT-qPCR) in spring source water and 8% (by PA) and 25% (by ICC-RT-qPCR) in the public water supply system. ICC-RT-qPCR, a very sensitive and rapid technique, was able to detect as low as 1 × 10(2) HAdV genome copies per milliliter of infectious viral particles in the environmental water samples. The molecular characterization studies indicated that HAdV-2 was the prevalent serotype. CONCLUSIONS: These results indicate a lack of proper public health measures. We suggest that HAdV can be efficiently used as a marker of environmental and drinking water contamination and ICC-RT-qPCR demonstrated greater sensitivity and speed of detection of infectious viral particles compared to PA.",2013 May 28,"['Fongaro, Gislaine', 'Nascimento, Mariana A do', 'Rigotto, Caroline', 'Ritterbusch, Giseli', 'da Silva, Alessandra D’ A', 'Esteves, Paulo A', 'Barardi, Célia R M']",Virol J,,,True
56f33cfd84beba69ee9c4c24da6f4840871ae679,PMC,P042: Severe influenza infections requiring intensive care during winter 2012/2013,http://dx.doi.org/10.1186/2047-2994-2-S1-P42,PMC3688439,,CC BY,,2013 Jun 20,"['Landelle, C', 'Iten, A', 'Kaiser, L', 'Thomas, Y', 'Genevois, E', 'Joubert, D', 'Richard, J-C', 'Harbarth, S', 'Pittet, D', 'Brochard, L']",Antimicrob Resist Infect Control,,,False
ca0c911ee3620b7acdb37a5b5d0b500128205f32,PMC,Evidence for Novel Hepaciviruses in Rodents,http://dx.doi.org/10.1371/journal.ppat.1003438,PMC3688547,23818848,CC BY,"Hepatitis C virus (HCV) is among the most relevant causes of liver cirrhosis and hepatocellular carcinoma. Research is complicated by a lack of accessible small animal models. The systematic investigation of viruses of small mammals could guide efforts to establish such models, while providing insight into viral evolutionary biology. We have assembled the so-far largest collection of small-mammal samples from around the world, qualified to be screened for bloodborne viruses, including sera and organs from 4,770 rodents (41 species); and sera from 2,939 bats (51 species). Three highly divergent rodent hepacivirus clades were detected in 27 (1.8%) of 1,465 European bank voles (Myodes glareolus) and 10 (1.9%) of 518 South African four-striped mice (Rhabdomys pumilio). Bats showed anti-HCV immunoblot reactivities but no virus detection, although the genetic relatedness suggested by the serologic results should have enabled RNA detection using the broadly reactive PCR assays developed for this study. 210 horses and 858 cats and dogs were tested, yielding further horse-associated hepaciviruses but none in dogs or cats. The rodent viruses were equidistant to HCV, exceeding by far the diversity of HCV and the canine/equine hepaciviruses taken together. Five full genomes were sequenced, representing all viral lineages. Salient genome features and distance criteria supported classification of all viruses as hepaciviruses. Quantitative RT-PCR, RNA in-situ hybridisation, and histopathology suggested hepatic tropism with liver inflammation resembling hepatitis C. Recombinant serology for two distinct hepacivirus lineages in 97 bank voles identified seroprevalence rates of 8.3 and 12.4%, respectively. Antibodies in bank vole sera neither cross-reacted with HCV, nor the heterologous bank vole hepacivirus. Co-occurrence of RNA and antibodies was found in 3 of 57 PCR-positive bank vole sera (5.3%). Our data enable new hypotheses regarding HCV evolution and encourage efforts to develop rodent surrogate models for HCV.",2013 Jun 20,"['Drexler, Jan Felix', 'Corman, Victor Max', 'Müller, Marcel Alexander', 'Lukashev, Alexander N.', 'Gmyl, Anatoly', 'Coutard, Bruno', 'Adam, Alexander', 'Ritz, Daniel', 'Leijten, Lonneke M.', 'van Riel, Debby', 'Kallies, Rene', 'Klose, Stefan M.', 'Gloza-Rausch, Florian', 'Binger, Tabea', 'Annan, Augustina', 'Adu-Sarkodie, Yaw', 'Oppong, Samuel', 'Bourgarel, Mathieu', 'Rupp, Daniel', 'Hoffmann, Bernd', 'Schlegel, Mathias', 'Kümmerer, Beate M.', 'Krüger, Detlev H.', 'Schmidt-Chanasit, Jonas', 'Setién, Alvaro Aguilar', 'Cottontail, Veronika M.', 'Hemachudha, Thiravat', 'Wacharapluesadee, Supaporn', 'Osterrieder, Klaus', 'Bartenschlager, Ralf', 'Matthee, Sonja', 'Beer, Martin', 'Kuiken, Thijs', 'Reusken, Chantal', 'Leroy, Eric M.', 'Ulrich, Rainer G.', 'Drosten, Christian']",PLoS Pathog,,,True
a523dca1cc7a585e2433acb959f3d396f35b9c79,PMC,"Risk Factors for Infectious Diseases in Backyard Poultry Farms in the Poyang Lake Area, China",http://dx.doi.org/10.1371/journal.pone.0067366,PMC3688663,23840680,CC BY,"Emergence and transmission of infectious diseases have an enormous impact on the poultry industry and present a serious threat to the health of humans and wild birds. Noncommercial poultry operations, such as backyard poultry facilities in China, are potential sources of virus exchange between commercial poultry and wild birds. It is particularly critical in wetland areas where backyard poultry have close contact with commercial poultry and migratory birds, therefore increasing the risk of contracting infectious diseases. To evaluate the transmission risks, a cross-sectional study was undertaken in the Poyang Lake area, China, involving 309 residents in the backyard poultry farms in three counties (Region A, B, and C) of Jiangxi Province. We examined the backyard poultry population, poultry species, presence of poultry deaths from infectious diseases, food sources, and biosecurity practices. Region B ranked highest for biosecurity while region C ranked lowest. The risks of infectious diseases were assessed by adjusted odds ratio based on multivariate logistic regression analysis. Potential risk factors in the three regions of the study site were compared. In Region A, significant factor was contact of poultry with wild birds (OR: 6.573, 95% CI: 2.148–20.115, P=0.001). In Region B, the most significant factor was contact of poultry with neighboring backyard waterfowls (OR: 3.967, 95% CI: 1.555–10.122, P=0.004). In Region C, significant factors were poultry purchase from local live bird markets (OR: 3.740, 95% CI: 1.243–11.255, P=0.019), and contact of poultry with wild birds (OR: 3.379, 95% CI: 1.058–10.791, P=0.040). In summary, backyard poultry was significantly affected by neighboring commercial poultry and close contact with wild birds. The results are expected to improve our understanding of the transmission risks of infectious diseases in a typical backyard poultry environment in rural China, and address the need to improve local farming practices and take preventive measures.",2013 Jun 20,"['Wang, Yong', 'Jiang, Zhiben', 'Jin, Zhenyu', 'Tan, Hua', 'Xu, Bing']",PLoS One,,,True
6fb874a7dee1d36545f8ea3c9714b288dca736e4,PMC,Rapid Generation of Human-Like Neutralizing Monoclonal Antibodies in Urgent Preparedness for Influenza Pandemics and Virulent Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0066276,PMC3688872,23824680,CC BY,"BACKGROUND: The outbreaks of emerging infectious diseases caused by pathogens such as SARS coronavirus, H5N1, H1N1, and recently H7N9 influenza viruses, have been associated with significant mortality and morbidity in humans. Neutralizing antibodies from individuals who have recovered from an infection confer therapeutic protection to others infected with the same pathogen. However, survivors may not always be available for providing plasma or for the cloning of monoclonal antibodies (mAbs). METHODOLOGY/PRINCIPAL FINDINGS: The genome and the immunoglobulin genes in rhesus macaques and humans are highly homologous; therefore, we investigated whether neutralizing mAbs that are highly homologous to those of humans (human-like) could be generated. Using the H5N1 influenza virus as a model, we first immunized rhesus macaques with recombinant adenoviruses carrying a synthetic gene encoding hemagglutinin (HA). Following screening an antibody phage display library derived from the B cells of immunized monkeys, we cloned selected macaque immunoglobulin heavy chain and light chain variable regions into the human IgG constant region, which generated human-macaque chimeric mAbs exhibiting over 97% homology to human antibodies. Selected mAbs demonstrated potent neutralizing activities against three clades (0, 1, 2) of the H5N1 influenza viruses. The in vivo protection experiments demonstrated that the mAbs effectively protected the mice even when administered up to 3 days after infection with H5N1 influenza virus. In particular, mAb 4E6 demonstrated sub-picomolar binding affinity to HA and superior in vivo protection efficacy without the loss of body weight and obvious lung damage. The analysis of the 4E6 escape mutants demonstrated that the 4E6 antibody bound to a conserved epitope region containing two amino acids on the globular head of HA. CONCLUSIONS/SIGNIFICANCE: Our study demonstrated the generation of neutralizing mAbs for potential application in humans in urgent preparedness against outbreaks of new influenza infections or other virulent infectious diseases.",2013 Jun 18,"['Meng, Weixu', 'Pan, Weiqi', 'Zhang, Anna J. X.', 'Li, Zhengfeng', 'Wei, Guowei', 'Feng, Liqiang', 'Dong, Zhenyuan', 'Li, Chufang', 'Hu, Xiangjing', 'Sun, Caijun', 'Luo, Qinfang', 'Yuen, Kwok-Yung', 'Zhong, Nanshan', 'Chen, Ling']",PLoS One,,,True
11a3797796973b32b0763f8127b908f4783e5734,PMC,Comprehensive Mapping Antigenic Epitopes of NS1 Protein of Japanese Encephalitis Virus with Monoclonal Antibodies,http://dx.doi.org/10.1371/journal.pone.0067553,PMC3688998,23825668,CC BY,"Japanese encephalitis virus (JEV) non-structural protein 1 (NS1) contributes to virus replication and elicits protective immune responses during infection. JEV NS1-specific antibody responses could be a target in the differential diagnosis of different flavivirus infections. However, the epitopes on JEV NS1 are poorly characterized. The present study describes the full mapping of linear B-cell epitopes in JEV NS1. We generated eleven NS1-specific monoclonal antibodies from mice immunized with recombinant NS1. For epitope mapping of monoclonal antibodies, a set of 51 partially-overlapping peptides covering the entire NS1 protein were expressed with a GST-tag and then screened using monoclonal antibodies. Through enzyme-linked immunosorbent assay (ELISA), five linear epitope-containing peptides were identified. By sequentially removing amino acid residues from the carboxy and amino terminal of peptides, the minimal units of the five linear epitopes were identified and confirmed using monoclonal antibodies. Five linear epitopes are located in amino acids residues (5)AIDITRK(11), (72)RDELNVL(78), (251)KSKHNRREGY(260), (269)DENGIVLD(276), and (341)DETTLVRS(348). Furthermore, it was found that the epitopes are highly conserved among JEV strains through sequence alignment. Notably, none of the homologous regions on NS1 proteins from other flaviviruses reacted with the MAbs when they were tested for cross-reactivity, and all five epitope peptides were not recognized by sera against West Nile virus or Dengue virus. These novel virus-specific linear B-cell epitopes of JEV NS1 would benefit the development of new vaccines and diagnostic assays.",2013 Jun 18,"['Hua, Rong-Hong', 'Liu, Li-Ke', 'Chen, Zhen-Shi', 'Li, Ye-Nan', 'Bu, Zhi-Gao']",PLoS One,,,True
5ef424a39823c1e6a0fc472b7ed744121356f11d,PMC,Multiantibody Strategies for HIV,http://dx.doi.org/10.1155/2013/632893,PMC3690221,23840243,CC BY,"Vaccination strategies depend entirely on the appropriate responsiveness of our immune system against particular antigens. For this active immunization to be truly effective, neutralizing antibodies (nAbs) need to efficiently counter the infectivity or propagation of the pathogen. Some viruses, including HIV, are able to take advantage of this immune response in order to evade nAbs. This review focuses on viral immune evasion strategies that result directly from a robust immune response to infection or vaccination. A rationale for multi-Ab therapy to circumvent this phenomenon is discussed. Progress in the formulation, production, and regulatory approval of monoclonal antibodies (mAbs) is presented.",2013 Jun 6,"['Hiatt, Andrew', 'Zeitlin, Larry', 'Whaley, Kevin J.']",Clin Dev Immunol,,,True
9c59d3a8be1e640d85fc5105dca9e530680c230a,PMC,"Knowledge Levels and Training Needs of Disaster Medicine among Health Professionals, Medical Students, and Local Residents in Shanghai, China",http://dx.doi.org/10.1371/journal.pone.0067041,PMC3691157,23826190,CC BY,"BACKGROUND: Disaster is a serious public health issue. Health professionals and community residents are main players in disaster responses but their knowledge levels of disaster medicine are not readily available. This study aimed to evaluate knowledge levels and training needs of disaster medicine among potential disaster responders and presented a necessity to popularize disaster medicine education. METHODS: A self-reporting questionnaire survey on knowledge level and training needs of disaster medicine was conducted in Shanghai, China, in 2012. A total of randomly selected 547 health professionals, 456 medical students, and 1,526 local residents provided intact information. The total response rate was 93.7%. RESULTS: Overall, 1.3% of these participants have received systematic disaster medicine training. News media (87.1%) was the most common channel to acquire disaster medicine knowledge. Although health professionals were more knowledgeable than community residents, their knowledge structure of disaster medicine was not intact. Medical teachers were more knowledgeable than medical practitioners and health administrators (p = 0.002). Clinicians performed better than public health physicians (p<0.001), whereas public health students performed better than clinical medical students (p<0.001). In community residents, education background significantly affected the knowledge level on disaster medicine (p<0.001). Training needs of disaster medicine were generally high among the surveyed. ‘Lecture’ and ‘practical training’ were preferred teaching methods. The selected key and interested contents on disaster medicine training were similar between health professionals and medical students, while the priorities chosen by local residents were quite different from health professionals and medical students (p<0.001). CONCLUSIONS: Traditional clinical-oriented medical education might lead to a huge gap between the knowledge level on disaster medicine and the current needs of disaster preparedness. Continuing medical education and public education plans on disaster medicine via media should be practice-oriented, and selectively applied to different populations and take the knowledge levels and training needs into consideration.",2013 Jun 24,"['Su, Tong', 'Han, Xue', 'Chen, Fei', 'Du, Yan', 'Zhang, Hongwei', 'Yin, Jianhua', 'Tan, Xiaojie', 'Chang, Wenjun', 'Ding, Yibo', 'Han, Yifang', 'Cao, Guangwen']",PLoS One,,,True
ddd0fb0cae99bad6466775c11b4d5a0c30be9219,PMC,Different Types of Door-Opening Motions as Contributing Factors to Containment Failures in Hospital Isolation Rooms,http://dx.doi.org/10.1371/journal.pone.0066663,PMC3691190,23826109,CC BY,"Hospital isolation rooms are vital for the containment (when under negative pressure) of patients with, or the protection (when under positive pressure) of patients, from airborne infectious agents. Such facilities were essential for the management of highly contagious patients during the 2003 severe acute respiratory syndrome (SARS) outbreaks and the more recent 2009 A/H1N1 influenza pandemic. Many different types of door designs are used in the construction of such isolation rooms, which may be related to the space available and affordability. Using colored food dye as a tracer, the qualitative effects of door-opening motions on the dissemination of potentially contaminated air into and out of a single isolation room were visualized and filmed using Reynolds-number-equivalent, small-scale, water-tank models fitted with programmable door-opening and moving human figure motions. Careful scaling considerations involved in the design and construction of these water-tank models enabled these results to be accurately extrapolated to the full-scale situation. Four simple types of door design were tested: variable speed single and double, sliding and hinged doors, in combination with the moving human figure. The resulting video footage was edited, synchronized and presented in a series of split-screen formats. From these experiments, it is clear that double-hinged doors pose the greatest risk of leakage into or out of the room, followed by (in order of decreasing risk) single-hinged, double-sliding and single-sliding doors. The relative effect of the moving human figure on spreading any potential contamination was greatest with the sliding doors, as the bulk airflows induced were large relative to those resulting from these door-opening motions. However, with the hinged doors, the airflows induced by these door-opening motions were significantly greater. Further experiments involving a simulated ventilated environment are required, but from these findings alone, it appears that sliding-doors are far more effective for hospital isolation room containment.",2013 Jun 24,"['Tang, Julian W.', 'Nicolle, Andre', 'Pantelic, Jovan', 'Klettner, Christian A.', 'Su, Ruikun', 'Kalliomaki, Petri', 'Saarinen, Pekka', 'Koskela, Hannu', 'Reijula, Kari', 'Mustakallio, Panu', 'Cheong, David K. W.', 'Sekhar, Chandra', 'Tham, Kwok Wai']",PLoS One,,,True
7f3e18a9a954832a2335fa3c26c42f127a79855c,PMC,MEK/ERK Dependent Activation of STAT1 Mediates Dasatinib-Induced Differentiation of Acute Myeloid Leukemia,http://dx.doi.org/10.1371/journal.pone.0066915,PMC3692534,23825585,CC BY,"Dasatinib (BMS-354825) is a FDA-approved multitargeted kinase inhibitor of BCR/ABL and Src kinases. It is now used in the treatment of chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapies, including imatinib. Here we report a novel effect of dasatinib on inducing the differentiation of acute myeloid leukemia (AML) cells through MEK/ERK-dependent activation of signal transducer and activator of transcription 1 (STAT1). We found that dasatinib could induce the differentiation of AML cells as demonstrated by the expression of differentiation marker CD11b, G0/G1 phase arrest and decreased ratio of nucleus to cytoplasm. Of note, dasatinib induced robust phosphorylation of STAT1 both at Tyr701 and Ser727 as well as the redistribution of STAT1 from the cytoplasm to the nucleus, thus leading to the transcription of STAT1-targeted genes. Knocking down STAT1 expression by shRNA significantly attenuated dasatinib-induced differentiation, indicating an important role of STAT1 in myeloid maturation. We further found that dasatinib-induced activation of STAT1 was regulated by the MEK/ERK kinases. The phosporylation of MEK and ERK occurred rapidly upon dasatinib treatment and increased progressively as differentiation was induced. MEK inhibitors PD98059 and U0216 not only inhibited the phosphorylation of STAT1, but also abrogated dasatinib-induced myeloid differentiation, suggesting that MEK/ERK dependent phosphorylation of STAT1 might be indispensable for the differentiating effect of dasatinib in AML cells. Taken together, our study suggests that STAT1 is an important mediator in dasatinib-induced differentiation of AML cells, whose activation requires the activation of MEK/ERK cascades.",2013 Jun 25,"['Fang, Yanfen', 'Zhong, Like', 'Lin, Meihua', 'Zhou, Xinglu', 'Jing, Hui', 'Ying, Meidan', 'Luo, Peihua', 'Yang, Bo', 'He, Qiaojun']",PLoS One,,,True
3f7b6af5cd76098945fd076e4fa43a541fb7a5a0,PMC,"Availability, consistency and evidence-base of policies and guidelines on the use of mask and respirator to protect hospital health care workers: a global analysis",http://dx.doi.org/10.1186/1756-0500-6-216,PMC3693993,23725338,CC BY,"BACKGROUND: Currently there is an ongoing debate and limited evidence on the use of masks and respirators for the prevention of respiratory infections in health care workers (HCWs). This study aimed to examine available policies and guidelines around the use of masks and respirators in HCWs and to describe areas of consistency between guidelines, as well as gaps in the recommendations, with reference to the WHO and the CDC guidelines. METHODS: Policies and guidelines related to mask and respirator use for the prevention of influenza, SARS and TB were examined. Guidelines from the World Health Organization (WHO), the Center for Disease Control and Prevention (CDC), three high-income countries and six low/middle-income countries were selected. RESULTS: Uniform recommendations are made by the WHO and the CDC in regards to protecting HCWs against seasonal influenza (a mask for low risk situations and a respirator for high risk situations) and TB (use of a respirator). However, for pandemic influenza and SARS, the WHO recommends mask use in low risk and respirators in high risk situations, whereas, the CDC recommends respirators in both low and high risk situations. Amongst the nine countries reviewed, there are variations in the recommendations for all three diseases. While, some countries align with the WHO recommendations, others align with those made by the CDC. The choice of respirator and the level of filtering ability vary amongst the guidelines and the different diseases. Lastly, none of the policies discuss reuse, extended use or the use of cloth masks. CONCLUSION: Currently, there are significant variations in the policies and recommendations around mask and respirator use for protection against influenza, SARS and TB. These differences may reflect the scarcity of level-one evidence available to inform policy development. The lack of any guidelines on the use of cloth masks, despite widespread use in many low and middle-income countries, remains a policy gap. Health organizations and countries should jointly evaluate the available evidence, prioritize research to inform evidence gaps, and develop consistent policy on masks and respirator use in the health care setting.",2013 May 31,"['Chughtai, Abrar Ahmad', 'Seale, Holly', 'MacIntyre, Chandini Raina']",BMC Res Notes,,,True
1f7d12535c961aa81e3719db27546b741674c1aa,PMC,Infectious Bronchitis Virus as a Vector for the Expression of Heterologous Genes,http://dx.doi.org/10.1371/journal.pone.0067875,PMC3694013,23840781,CC BY,"The avian coronavirus infectious bronchitis virus (IBV) is the causative agent of the respiratory disease infectious bronchitis of domestic fowl, and is controlled by routine vaccination. To explore the potential use of IBV as a vaccine vector a reverse genetics system was utilised to generate infectious recombinant IBVs (rIBVs) expressing the reporter genes enhanced green fluorescent protein (eGFP) or humanised Renilla luciferase (hRluc). Infectious rIBVs were obtained following the replacement of Gene 5 or the intergenic region (IR) with eGFP or hRluc, or the replacement of ORFs 3a and 3b with hRluc. The replacement of Gene 5 with an IBV codon-optimised version of the hRluc gene also resulted in successful rescue of infectious rIBV. Reporter gene expression was confirmed by fluorescence microscopy, or luciferase activity assays, for all successfully rescued rIBVs following infection of primary chick kidney (CK) cells. The genetic stability of rIBVs was analysed by serial passage on CK cells. Recombinant IBV stability varied depending on the genome region being replaced, with the reporter genes maintained up to at least passage 8 (P8) following replacement of Gene 5, P7 for replacement of the IR and P5 for replacement of ORFs 3a and 3b. Codon-optimisation of the hRluc gene, when replacing Gene 5, resulted in an increase in genome stability, with hRluc expression stable up to P10 compared to P8 for standard hRluc. Repeated passaging of rIBVs expressing hRluc at an MOI of 0.01 demonstrated an increase in stability, with hRluc expression stable up to at least P12 following the replacement of Gene 5. This study has demonstrated that heterologous genes can be incorporated into, and expressed from a range of IBV genome locations and that replacement of accessory Gene 5 offers a promising target for realising the potential of IBV as a vaccine vector for other avian pathogens.",2013 Jun 26,"['Bentley, Kirsten', 'Armesto, Maria', 'Britton, Paul']",PLoS One,,,True
4156b347411e4071b10550a6acc2725c5e82df99,PMC,Neutrophils Turn Plasma Proteins into Weapons against HIV-1,http://dx.doi.org/10.1371/journal.pone.0066073,PMC3694086,23840401,CC BY,"As a consequence of innate immune activation granulocytes and macrophages produce hypochlorite/hypochlorous acid (HOCl) via secretion of myeloperoxidase (MPO) to the outside of the cells, where HOCl immediately reacts with proteins. Most proteins that become altered by this system do not belong to the invading microorganism but to the host. While there is no doubt that the myeloperoxidase system is capable of directly inactivating HIV-1, we hypothesized that it may have an additional indirect mode of action. We show in this article that HOCl is able to chemically alter proteins and thus turn them into Idea-Ps (Idea-P = immune defence-altered protein), potent amyloid-like and SH-groups capturing antiviral weapons against HIV-1. HOCl-altered plasma proteins (Idea-PP) have the capacity to bind efficiently and with high affinity to the HIV-1 envelope protein gp120, and to its receptor CD4 as well as to the protein disulfide isomerase (PDI). Idea-PP was able to inhibit viral infection and replication in a cell culture system as shown by reduced number of infected cells and of syncytia, resulting in reduction of viral capsid protein p24 in the culture supernatant. The unmodified plasma protein fraction had no effect. HOCl-altered isolated proteins antithrombin III and human serum albumin, taken as representative examples of the whole pool of plasma proteins, were both able to exert the same activity of binding to gp120 and inhibition of viral proliferation. These data offer an opportunity to improve the understanding of the intricacies of host-pathogen interactions and allow the generation of the following hypothetical scheme: natural immune defense mechanisms generate by posttranslational modification of plasma proteins a potent virucidal weapon that immobilizes the virus as well as inhibits viral fusion and thus entry into the host cells. Furthermore simulation of this mechanism in vitro might provide an interesting new therapeutic approach against microorganisms.",2013 Jun 26,"['Speth, Cornelia', 'Brodde, Martin F.', 'Hagleitner, Magdalena', 'Rambach, Günter', 'Van Aken, Hugo', 'Dierich, Manfred', 'Kehrel, Beate E.']",PLoS One,,,True
91ac78d2a3c677d322fc8b14bc23e6b4244b5bdc,PMC,Comparison of Heterologous Prime-Boost Strategies against Human Immunodeficiency Virus Type 1 Gag Using Negative Stranded RNA Viruses,http://dx.doi.org/10.1371/journal.pone.0067123,PMC3694142,23840600,CC BY,"This study analyzed a heterologous prime-boost vaccine approach against HIV-1 using three different antigenically unrelated negative-stranded viruses (NSV) expressing HIV-1 Gag as vaccine vectors: rabies virus (RABV), vesicular stomatitis virus (VSV) and Newcastle disease virus (NDV). We hypothesized that this approach would result in more robust cellular immune responses than those achieved with the use of any of the vaccines alone in a homologous prime-boost regimen. To this end, we primed BALB/c mice with each of the NSV-based vectors. Primed mice were rested for thirty-five days after which we administered a second immunization with the same or heterologous NSV-Gag viruses. The magnitude and quality of the Gag-specific CD8(+) T cells in response to these vectors post boost were measured. In addition, we performed challenge experiments using vaccinia virus expressing HIV-1 Gag (VV-Gag) thirty-three days after the boost inoculation. Our results showed that the choice of the vaccine used for priming was important for the detected Gag-specific CD8(+) T cell recall responses post boost and that NDV-Gag appeared to result in a more robust recall of CD8(+) T cell responses independent of the prime vaccine used. However, the different prime-boost strategies were not distinct for the parameters studied in the challenge experiments using VV-Gag but did indicate some benefits compared to single immunizations. Taken together, our data show that NSV vectors can individually stimulate HIV-Gag specific CD8(+) T cells that are effectively recalled by other NSV vectors in a heterologous prime-boost approach. These results provide evidence that RABV, VSV and NDV can be used in combination to develop vaccines needing prime-boost regimens to stimulate effective immune responses.",2013 Jun 26,"['Lawrence, Tessa M.', 'Wanjalla, Celestine N.', 'Gomme, Emily A.', 'Wirblich, Christoph', 'Gatt, Anthony', 'Carnero, Elena', 'García-Sastre, Adolfo', 'Lyles, Douglas S.', 'McGettigan, James P.', 'Schnell, Matthias J.']",PLoS One,,,True
7c73591901ddde49d3ebba7410f2e2da1ceb6707,PMC,Towards Systematic Discovery of Signaling Networks in Budding Yeast Filamentous Growth Stress Response Using Interventional Phosphorylation Data,http://dx.doi.org/10.1371/journal.pcbi.1003077,PMC3694812,23825934,CC BY,"Reversible phosphorylation is one of the major mechanisms of signal transduction, and signaling networks are critical regulators of cell growth and development. However, few of these networks have been delineated completely. Towards this end, quantitative phosphoproteomics is emerging as a useful tool enabling large-scale determination of relative phosphorylation levels. However, phosphoproteomics differs from classical proteomics by a more extensive sampling limitation due to the limited number of detectable sites per protein. Here, we propose a comprehensive quantitative analysis pipeline customized for phosphoproteome data from interventional experiments for identifying key proteins in specific pathways, discovering the protein-protein interactions and inferring the signaling network. We also made an effort to partially compensate for the missing value problem, a chronic issue for proteomics studies. The dataset used for this study was generated using SILAC (Stable Isotope Labeling with Amino acids in Cell culture) technique with interventional experiments (kinase-dead mutations). The major components of the pipeline include phosphopeptide meta-analysis, correlation network analysis and causal relationship discovery. We have successfully applied our pipeline to interventional experiments identifying phosphorylation events underlying the transition to a filamentous growth form in Saccharomyces cerevisiae. We identified 5 high-confidence proteins from meta-analysis, and 19 hub proteins from correlation analysis (Pbi2p and Hsp42p were identified by both analyses). All these proteins are involved in stress responses. Nine of them have direct or indirect evidence of involvement in filamentous growth. In addition, we tested four of our predicted proteins, Nth1p, Pbi2p, Pdr12p and Rcn2p, by interventional phenotypic experiments and all of them present differential invasive growth, providing prospective validation of our approach. This comprehensive pipeline presents a systematic way for discovering signaling networks using interventional phosphoproteome data and can suggest candidate proteins for further investigation. We anticipate the methodology to be applicable as well to other interventional studies via different experimental platforms.",2013 Jun 27,"['Zhang, Yan', 'Kweon, Hye Kyong', 'Shively, Christian', 'Kumar, Anuj', 'Andrews, Philip C.']",PLoS Comput Biol,,,True
e0531f9c84005ac77b1bdb3075c486e6ac116760,PMC,Towards Systematic Discovery of Signaling Networks in Budding Yeast Filamentous Growth Stress Response Using Interventional Phosphorylation Data,http://dx.doi.org/10.1371/journal.pcbi.1003077,PMC3694812,23825934,CC BY,"Reversible phosphorylation is one of the major mechanisms of signal transduction, and signaling networks are critical regulators of cell growth and development. However, few of these networks have been delineated completely. Towards this end, quantitative phosphoproteomics is emerging as a useful tool enabling large-scale determination of relative phosphorylation levels. However, phosphoproteomics differs from classical proteomics by a more extensive sampling limitation due to the limited number of detectable sites per protein. Here, we propose a comprehensive quantitative analysis pipeline customized for phosphoproteome data from interventional experiments for identifying key proteins in specific pathways, discovering the protein-protein interactions and inferring the signaling network. We also made an effort to partially compensate for the missing value problem, a chronic issue for proteomics studies. The dataset used for this study was generated using SILAC (Stable Isotope Labeling with Amino acids in Cell culture) technique with interventional experiments (kinase-dead mutations). The major components of the pipeline include phosphopeptide meta-analysis, correlation network analysis and causal relationship discovery. We have successfully applied our pipeline to interventional experiments identifying phosphorylation events underlying the transition to a filamentous growth form in Saccharomyces cerevisiae. We identified 5 high-confidence proteins from meta-analysis, and 19 hub proteins from correlation analysis (Pbi2p and Hsp42p were identified by both analyses). All these proteins are involved in stress responses. Nine of them have direct or indirect evidence of involvement in filamentous growth. In addition, we tested four of our predicted proteins, Nth1p, Pbi2p, Pdr12p and Rcn2p, by interventional phenotypic experiments and all of them present differential invasive growth, providing prospective validation of our approach. This comprehensive pipeline presents a systematic way for discovering signaling networks using interventional phosphoproteome data and can suggest candidate proteins for further investigation. We anticipate the methodology to be applicable as well to other interventional studies via different experimental platforms.",2013 Jun 27,"['Zhang, Yan', 'Kweon, Hye Kyong', 'Shively, Christian', 'Kumar, Anuj', 'Andrews, Philip C.']",PLoS Comput Biol,,,True
5908982f4dbbfde0faabcfadc0988b8a19223411,PMC,Evasion of Antiviral Innate Immunity by Theiler's Virus L* Protein through Direct Inhibition of RNase L,http://dx.doi.org/10.1371/journal.ppat.1003474,PMC3694852,23825954,CC BY,"Theiler's virus is a neurotropic picornavirus responsible for chronic infections of the central nervous system. The establishment of a persistent infection and the subsequent demyelinating disease triggered by the virus depend on the expression of L*, a viral accessory protein encoded by an alternative open reading frame of the virus. We discovered that L* potently inhibits the interferon-inducible OAS/RNase L pathway. The antagonism of RNase L by L* was particularly prominent in macrophages where baseline oligoadenylate synthetase (OAS) and RNase L expression levels are elevated, but was detectable in fibroblasts after IFN pretreatment. L* mutations significantly affected Theiler's virus replication in primary macrophages derived from wild-type but not from RNase L-deficient mice. L* counteracted the OAS/RNase L pathway through direct interaction with the ankyrin domain of RNase L, resulting in the inhibition of this enzyme. Interestingly, RNase L inhibition was species-specific as Theiler's virus L* protein blocked murine RNase L but not human RNase L or RNase L of other mammals or birds. Direct RNase L inhibition by L* and species specificity were confirmed in an in vitro assay performed with purified proteins. These results demonstrate a novel viral mechanism to elude the antiviral OAS/RNase L pathway. By targeting the effector enzyme of this antiviral pathway, L* potently inhibits RNase L, underscoring the importance of this enzyme in innate immunity against Theiler's virus.",2013 Jun 27,"['Sorgeloos, Frédéric', 'Jha, Babal Kant', 'Silverman, Robert H.', 'Michiels, Thomas']",PLoS Pathog,,,True
3154395f4f53dd3c358e5ba72e394f9334430cef,PMC,A Simulation Optimization Approach to Epidemic Forecasting,http://dx.doi.org/10.1371/journal.pone.0067164,PMC3694918,23826222,CC BY,"Reliable forecasts of influenza can aid in the control of both seasonal and pandemic outbreaks. We introduce a simulation optimization (SIMOP) approach for forecasting the influenza epidemic curve. This study represents the final step of a project aimed at using a combination of simulation, classification, statistical and optimization techniques to forecast the epidemic curve and infer underlying model parameters during an influenza outbreak. The SIMOP procedure combines an individual-based model and the Nelder-Mead simplex optimization method. The method is used to forecast epidemics simulated over synthetic social networks representing Montgomery County in Virginia, Miami, Seattle and surrounding metropolitan regions. The results are presented for the first four weeks. Depending on the synthetic network, the peak time could be predicted within a 95% CI as early as seven weeks before the actual peak. The peak infected and total infected were also accurately forecasted for Montgomery County in Virginia within the forecasting period. Forecasting of the epidemic curve for both seasonal and pandemic influenza outbreaks is a complex problem, however this is a preliminary step and the results suggest that more can be achieved in this area.",2013 Jun 27,"['Nsoesie, Elaine O.', 'Beckman, Richard J.', 'Shashaani, Sara', 'Nagaraj, Kalyani S.', 'Marathe, Madhav V.']",PLoS One,,,True
94f391ebd1b25ac7fb8159d7b24b7414c582a630,PMC,A Simulation Optimization Approach to Epidemic Forecasting,http://dx.doi.org/10.1371/journal.pone.0067164,PMC3694918,23826222,CC BY,"Reliable forecasts of influenza can aid in the control of both seasonal and pandemic outbreaks. We introduce a simulation optimization (SIMOP) approach for forecasting the influenza epidemic curve. This study represents the final step of a project aimed at using a combination of simulation, classification, statistical and optimization techniques to forecast the epidemic curve and infer underlying model parameters during an influenza outbreak. The SIMOP procedure combines an individual-based model and the Nelder-Mead simplex optimization method. The method is used to forecast epidemics simulated over synthetic social networks representing Montgomery County in Virginia, Miami, Seattle and surrounding metropolitan regions. The results are presented for the first four weeks. Depending on the synthetic network, the peak time could be predicted within a 95% CI as early as seven weeks before the actual peak. The peak infected and total infected were also accurately forecasted for Montgomery County in Virginia within the forecasting period. Forecasting of the epidemic curve for both seasonal and pandemic influenza outbreaks is a complex problem, however this is a preliminary step and the results suggest that more can be achieved in this area.",2013 Jun 27,"['Nsoesie, Elaine O.', 'Beckman, Richard J.', 'Shashaani, Sara', 'Nagaraj, Kalyani S.', 'Marathe, Madhav V.']",PLoS One,,,True
d7b6ba6c543bcfd967c19fc3663abee090ed3a25,PMC,Duration of Maternal Antibodies against Canine Distemper Virus and Hendra Virus in Pteropid Bats,http://dx.doi.org/10.1371/journal.pone.0067584,PMC3695084,23826322,CC BY,"Old World frugivorous bats have been identified as natural hosts for emerging zoonotic viruses of significant public health concern, including henipaviruses (Nipah and Hendra virus), Ebola virus, and Marburg virus. Epidemiological studies of these viruses in bats often utilize serology to describe viral dynamics, with particular attention paid to juveniles, whose birth increases the overall susceptibility of the population to a viral outbreak once maternal immunity wanes. However, little is understood about bat immunology, including the duration of maternal antibodies in neonates. Understanding duration of maternally derived immunity is critical for characterizing viral dynamics in bat populations, which may help assess the risk of spillover to humans. We conducted two separate studies of pregnant Pteropus bat species and their offspring to measure the half-life and duration of antibodies to 1) canine distemper virus antigen in vaccinated captive Pteropus hypomelanus; and 2) Hendra virus in wild-caught, naturally infected Pteropus alecto. Both of these pteropid bat species are known reservoirs for henipaviruses. We found that in both species, antibodies were transferred from dam to pup. In P. hypomelanus pups, titers against CDV waned over a mean period of 228.6 days (95% CI: 185.4–271.8) and had a mean terminal phase half-life of 96.0 days (CI 95%: 30.7–299.7). In P. alecto pups, antibodies waned over 255.13 days (95% CI: 221.0–289.3) and had a mean terminal phase half-life of 52.24 days (CI 95%: 33.76–80.83). Each species showed a duration of transferred maternal immunity of between 7.5 and 8.5 months, which was longer than has been previously estimated. These data will allow for more accurate interpretation of age-related Henipavirus serological data collected from wild pteropid bats.",2013 Jun 27,"['Epstein, Jonathan H.', 'Baker, Michelle L.', 'Zambrana-Torrelio, Carlos', 'Middleton, Deborah', 'Barr, Jennifer A.', 'DuBovi, Edward', 'Boyd, Victoria', 'Pope, Brian', 'Todd, Shawn', 'Crameri, Gary', 'Walsh, Allyson', 'Pelican, Katey', 'Fielder, Mark D.', 'Davies, Angela J.', 'Wang, Lin-Fa', 'Daszak, Peter']",PLoS One,,,True
3331e1bb231ae4227e4b6e8e98412b17468747a1,PMC,Protein co-expression network analysis (ProCoNA),http://dx.doi.org/10.1186/2043-9113-3-11,PMC3695838,23724967,CC BY,"BACKGROUND: Biological networks are important for elucidating disease etiology due to their ability to model complex high dimensional data and biological systems. Proteomics provides a critical data source for such models, but currently lacks robust de novo methods for network construction, which could bring important insights in systems biology. RESULTS: We have evaluated the construction of network models using methods derived from weighted gene co-expression network analysis (WGCNA). We show that approximately scale-free peptide networks, composed of statistically significant modules, are feasible and biologically meaningful using two mouse lung experiments and one human plasma experiment. Within each network, peptides derived from the same protein are shown to have a statistically higher topological overlap and concordance in abundance, which is potentially important for inferring protein abundance. The module representatives, called eigenpeptides, correlate significantly with biological phenotypes. Furthermore, within modules, we find significant enrichment for biological function and known interactions (gene ontology and protein-protein interactions). CONCLUSIONS: Biological networks are important tools in the analysis of complex systems. In this paper we evaluate the application of weighted co-expression network analysis to quantitative proteomics data. Protein co-expression networks allow novel approaches for biological interpretation, quality control, inference of protein abundance, a framework for potentially resolving degenerate peptide-protein mappings, and a biomarker signature discovery.",2013 Jun 1,"['Gibbs, David L', 'Baratt, Arie', 'Baric, Ralph S', 'Kawaoka, Yoshihiro', 'Smith, Richard D', 'Orwoll, Eric S', 'Katze, Michael G', 'McWeeney, Shannon K']",J Clin Bioinforma,,,True
914d646494f09cbb34bbe5da9dfea4c93ad35bb9,PMC,Rhabdomyolysis Associated with Parainfluenza Virus,http://dx.doi.org/10.1155/2013/650965,PMC3697188,23840985,CC BY,"Influenza virus is the most frequently reported viral cause of rhabdomyolysis. A 7-year-old child is presented with rhabdomyolysis associated with parainfluenza type 2 virus. Nine cases of rhabdomyolysis associated with parainfluenza virus have been reported. Complications may include electrolyte disturbances, acute renal failure, and compartment syndrome.",2013 Jun 13,"['Douvoyiannis, Miltiadis', 'Kielbasa, Johanna M.', 'Chandrasekharan, Gopal M.', 'Holmes, Cynthia L.', 'Gomez, Michael R.']",Case Rep Infect Dis,,,True
3a744992aeec8bfdcfc35035187791f3c8613f41,PMC,Scorpion Peptides: Potential Use for New Drug Development,http://dx.doi.org/10.1155/2013/958797,PMC3697785,23843786,CC BY,"Several peptides contained in scorpion fluids showed diverse array of biological activities with high specificities to their targeted sites. Many investigations outlined their potent effects against microbes and showed their potential to modulate various biological mechanisms that are involved in immune, nervous, cardiovascular, and neoplastic diseases. Because of their important structural and functional diversity, it is projected that scorpion-derived peptides could be used to develop new specific drugs. This review summarizes relevant findings improving their use as valuable tools for new drugs development.",2013 Jun 15,"['Hmed, BenNasr', 'Serria, Hammami Turky', 'Mounir, Zeghal Khaled']",J Toxicol,,,True
e5407e15d4e044411687f36176bc9d27bb6a3fd4,PMC,TRAF molecules in cell signaling and in human diseases,http://dx.doi.org/10.1186/1750-2187-8-7,PMC3697994,23758787,CC BY,"The tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family of intracellular proteins were originally identified as signaling adaptors that bind directly to the cytoplasmic regions of receptors of the TNF-R superfamily. The past decade has witnessed rapid expansion of receptor families identified to employ TRAFs for signaling. These include Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), T cell receptor, IL-1 receptor family, IL-17 receptors, IFN receptors and TGFβ receptors. In addition to their role as adaptor proteins, most TRAFs also act as E3 ubiquitin ligases to activate downstream signaling events. TRAF-dependent signaling pathways typically lead to the activation of nuclear factor-κBs (NF-κBs), mitogen-activated protein kinases (MAPKs), or interferon-regulatory factors (IRFs). Compelling evidence obtained from germ-line and cell-specific TRAF-deficient mice demonstrates that each TRAF plays indispensable and non-redundant physiological roles, regulating innate and adaptive immunity, embryonic development, tissue homeostasis, stress response, and bone metabolism. Notably, mounting evidence implicates TRAFs in the pathogenesis of human diseases such as cancers and autoimmune diseases, which has sparked new appreciation and interest in TRAF research. This review presents an overview of the current knowledge of TRAFs, with an emphasis on recent findings concerning TRAF molecules in signaling and in human diseases.",2013 Jun 13,"Xie, Ping",J Mol Signal,,,True
0e6f08bde4abd9fb12aa599c325e381692c83125,PMC,"Comparison among nasopharyngeal swab, nasal wash, and oropharyngeal swab for respiratory virus detection in adults with acute pharyngitis",http://dx.doi.org/10.1186/1471-2334-13-281,PMC3698019,23786598,CC BY,"BACKGROUND: Acute pharyngitis is frequently seen in primary care. Acute viral pharyngitis may be easily misdiagnosed as acute bacterial pharyngitis. Laboratory-confirmed diagnosis of respiratory viruses is recommended. The purpose of this study was to compare the sensitivities among oropharyngeal swab (OPS), nasopharyngeal swab (NPS), and nasal wash (NW) in adults with acute pharyngitis. METHODS: OPS, NPS, and NW were obtained from each participant with acute pharyngitis. The specimens were tested for 15 respiratory viruses by TaqMan real-time polymerase chain reaction. A sample was considered to be a true positive if any of the specimens was positive. The sensitivities among samples were compared by chi-square test or Fisher’s exact test, as appropriate. RESULTS: One hundred three triple samples collected consecutively by OPS, NPS, and NW were obtained. In 73 patients, one or more viruses were detected by any of the three methods. Among all viruses, the sensitivity of NPS was significantly higher than that of NW (74% vs. 49%, respectively; p < 0.01) and OPS (74% vs. 49%, respectively; p < 0.01). CONCLUSIONS: Flocked NPS collection may be the most effective alternative to NW and OPS for detection of respiratory viruses in adults with acute pharyngitis using TaqMan real-time polymerase chain reaction.",2013 Jun 20,"['Li, Li', 'Chen, Qiao-Yan', 'Li, Yun-Ying', 'Wang, Yan-Fang', 'Yang, Zi-Feng', 'Zhong, Nan-Shan']",BMC Infect Dis,,,True
d4771e9bbc00e3937638507817289579abc270bc,PMC,Effect of black tea extract on herpes simplex virus-1 infection of cultured cells,http://dx.doi.org/10.1186/1472-6882-13-139,PMC3698045,23777309,CC BY,"BACKGROUND: The purpose of this investigation was to determine if black tea extract (BTE), consisting primarily of flavanol compounds called theaflavins, could inhibit herpes simplex virus type-1 (HSV-1) infection in cultured A549 (human epithelial) and Vero cells. METHODS: The effect of BTE both on A549 and Vero cultured cells and on HSV-1 was assessed by using phase contrast and fluorescent microscopy, and cell viability and proliferation assays. After establishing the maximum non-cytotoxic concentration of BTE, A549 and Vero cells and HSV-1 virions were treated with varying concentrations of BTE, respectively. A549 and Vero cells were infected with HSV-1 with green fluorescent protein (GFP) insert at the UL46 gene. The effect of infectivity was determined by viral DNA extraction followed by PCR, plaque assays, adsorption assays, and electrophoresis of PCR products. RESULTS: BTE was not cytotoxic to A549 and Vero cells, as confirmed by cell viability and proliferation assays, in which BTE treated groups paralleled the positive control group. For both cell lines, plaque assays and fluorescent microscopy indicated an inverse relationship between BTE concentration (from 0.14 μM – 1.4 mM) and HSV-1 infectivity. Specifically, PCR and electrophoresis showed a reduction in the viral genome following treatment with BTE. In addition, there was a noticeable decrease in the amount of viral plaques for BTE treated samples in the adsorption assays. CONCLUSIONS: BTE consisting primarily of theaflavins is not cytotoxic and can reduce or block the production of infectious HSV-1 virions in cultured A549 and Vero cells, thus inhibiting the infectivity of the virus by interfering in the attachment, penetration and viral DNA replication of HSV-1 particles. These findings indicate that BTE enriched with theaflavins has the potential to be developed as a safe, therapeutic antiviral agent to prevent the spread of HSV-1.",2013 Jun 18,"['Cantatore, Anthony', 'Randall, Sade D', 'Traum, Daniel', 'Adams, Sandra D']",BMC Complement Altern Med,,,True
f2659bd84b8347a97b54698fbc1dea43ef10a85e,PMC,Hepatic Deficiency of COP9 Signalosome Subunit 8 Induces Ubiquitin-Proteasome System Impairment and Bim-Mediated Apoptosis in Murine Livers,http://dx.doi.org/10.1371/journal.pone.0067793,PMC3698095,23840878,CC BY,"The COP9 signalosome (CSN), an evolutionally highly conserved protein complex composed of 8 unique subunits (CSN1 through CSN8) in higher eukaryotes, is purported to modulate protein degradation mediated by the ubiquitin-proteasome system (UPS) but this has not been demonstrated in a critical mitotic parenchymal organ of vertebrates. Hepatocyte-specific knockout of the Cops8 gene (HS-Csn8KO) was shown to cause massive hepatocyte apoptosis and liver malfunction but the underlying mechanism remains unclear. Here, we report that Csn8/CSN exerts profound impacts on hepatic UPS function and is critical to the stability of the pro-apoptotic protein Bim. Significant decreases in CIS (cytokine-inducible Src homology 2 domain-containing protein), a Bim receptor of a cullin2-based ubiquitin ligase, were found to co-exist with a marked increase of Bim proteins. Csn8 deficiency also significantly decreased 19S proteasome subunit Rpt5 and markedly increased high molecular weight neddylated and ubiquitinated proteins. The use of a surrogate UPS substrate further reveals severe impairment of UPS-mediated proteolysis in HS-Csn8KO livers. Inclusion body-like materials were accumulated in Csn8 deficient hepatocytes. In addition to Bim, massive hepatocyte apoptosis in HS-Csn8KO livers is also associated with elevated expression of other members of the Bcl2 family, including pro-apoptotic Bax as well as anti-apoptotic Bcl2 and Bcl-XL. Increased interaction between Bcl2 and Bim, but not between Bcl2 and Bax, was detected. Hence, it is concluded that hepatic CSN8 deficiency impairs the UPS in the liver and the resultant Bim upregulation likely plays an important role in triggering hepatocyte apoptosis via sequestering Bcl2 away from Bax.",2013 Jul 1,"['Lei, Daoxiong', 'Li, Faqian', 'Su, Huabo', 'Liu, Jinbao', 'Wei, Ning', 'Wang, Xuejun']",PLoS One,,,True
f1541ead6bf6988b4d08b12873806a89a4b7ff1b,PMC,In Vitro Activity of Sodium New Houttuyfonate Alone and in Combination with Oxacillin or Netilmicin against Methicillin-Resistant Staphylococcus aureus,http://dx.doi.org/10.1371/journal.pone.0068053,PMC3699466,23844154,CC BY,"BACKGROUND: Staphylococcus aureus can cause severe infections, including bacteremia and sepsis. The spread of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for novel treatment options. Sodium new houttuyfonate (SNH) is an analogue of houttuynin, the main antibacterial ingredient of Houttuynia cordata Thunb. The aim of this study was to evaluate in vitro activity of SNH and its potential for synergy with antibiotics against hospital-associated MRSA. METHODOLOGY: A total of 103 MRSA clinical isolates recovered in two hospitals in Beijing were evaluated for susceptibility to SNH, oxacillin, cephalothin, meropenem, vancomycin, levofloxacin, minocycline, netilmicin, and trimethoprim/sulfamethoxazole by broth microdilution. Ten isolates were evaluated for potential for synergy between SNH and the antibiotics above by checkerboard assay. Time-kill analysis was performed in three isolates to characterize the kill kinetics of SNH alone and in combination with the antibiotics that engendered synergy in checkerboard assays. Besides, two reference strains were included in all assays. PRINCIPAL FINDINGS: SNH inhibited all test strains with minimum inhibitory concentrations (MICs) ranging from 16 to 64 µg/mL in susceptibility tests, and displayed inhibition to bacterial growth in concentration-dependent manner in time-kill analysis. In synergy studies, the combinations of SNH-oxacillin, SNH-cephalothin, SNH-meropenem and SNH-netilmicin showed synergistic effects against 12 MRSA strains with median fractional inhibitory concentration (FIC) indices of 0.38, 0.38, 0.25 and 0.38 in checkerboard assays. In time-kill analysis, SNH at 1/2 MIC in combination with oxacillin at 1/128 to 1/64 MIC or netilmicin at 1/8 to 1/2 MIC decreased the viable colonies by ≥2log(10) CFU/mL. CONCLUSIONS/SIGNIFICANCE: SNH demonstrated in vitro antibacterial activity against 103 hospital-associated MRSA isolates. Combinations of sub-MIC levels of SNH and oxacillin or netilmicin significantly improved the in vitro antibacterial activity against MRSA compared with either drug alone. The SNH-based combinations showed promise in combating MRSA.",2013 Jul 2,"['Lu, Xi', 'Yang, Xinyi', 'Li, Xue', 'Lu, Yun', 'Ren, Zhitao', 'Zhao, Longyin', 'Hu, Xinxin', 'Jiang, Jiandong', 'You, Xuefu']",PLoS One,,,True
5cbecfc7afe8168effb452c060f809c55ccbf880,PMC,In Vitro Activity of Sodium New Houttuyfonate Alone and in Combination with Oxacillin or Netilmicin against Methicillin-Resistant Staphylococcus aureus,http://dx.doi.org/10.1371/journal.pone.0068053,PMC3699466,23844154,CC BY,"BACKGROUND: Staphylococcus aureus can cause severe infections, including bacteremia and sepsis. The spread of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for novel treatment options. Sodium new houttuyfonate (SNH) is an analogue of houttuynin, the main antibacterial ingredient of Houttuynia cordata Thunb. The aim of this study was to evaluate in vitro activity of SNH and its potential for synergy with antibiotics against hospital-associated MRSA. METHODOLOGY: A total of 103 MRSA clinical isolates recovered in two hospitals in Beijing were evaluated for susceptibility to SNH, oxacillin, cephalothin, meropenem, vancomycin, levofloxacin, minocycline, netilmicin, and trimethoprim/sulfamethoxazole by broth microdilution. Ten isolates were evaluated for potential for synergy between SNH and the antibiotics above by checkerboard assay. Time-kill analysis was performed in three isolates to characterize the kill kinetics of SNH alone and in combination with the antibiotics that engendered synergy in checkerboard assays. Besides, two reference strains were included in all assays. PRINCIPAL FINDINGS: SNH inhibited all test strains with minimum inhibitory concentrations (MICs) ranging from 16 to 64 µg/mL in susceptibility tests, and displayed inhibition to bacterial growth in concentration-dependent manner in time-kill analysis. In synergy studies, the combinations of SNH-oxacillin, SNH-cephalothin, SNH-meropenem and SNH-netilmicin showed synergistic effects against 12 MRSA strains with median fractional inhibitory concentration (FIC) indices of 0.38, 0.38, 0.25 and 0.38 in checkerboard assays. In time-kill analysis, SNH at 1/2 MIC in combination with oxacillin at 1/128 to 1/64 MIC or netilmicin at 1/8 to 1/2 MIC decreased the viable colonies by ≥2log(10) CFU/mL. CONCLUSIONS/SIGNIFICANCE: SNH demonstrated in vitro antibacterial activity against 103 hospital-associated MRSA isolates. Combinations of sub-MIC levels of SNH and oxacillin or netilmicin significantly improved the in vitro antibacterial activity against MRSA compared with either drug alone. The SNH-based combinations showed promise in combating MRSA.",2013 Jul 2,"['Lu, Xi', 'Yang, Xinyi', 'Li, Xue', 'Lu, Yun', 'Ren, Zhitao', 'Zhao, Longyin', 'Hu, Xinxin', 'Jiang, Jiandong', 'You, Xuefu']",PLoS One,,,False
fe82f6e8d1a8144c8d4de65cb971b8c96fb1cb57,PMC,In Vitro Activity of Sodium New Houttuyfonate Alone and in Combination with Oxacillin or Netilmicin against Methicillin-Resistant Staphylococcus aureus,http://dx.doi.org/10.1371/journal.pone.0068053,PMC3699466,23844154,CC BY,"BACKGROUND: Staphylococcus aureus can cause severe infections, including bacteremia and sepsis. The spread of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for novel treatment options. Sodium new houttuyfonate (SNH) is an analogue of houttuynin, the main antibacterial ingredient of Houttuynia cordata Thunb. The aim of this study was to evaluate in vitro activity of SNH and its potential for synergy with antibiotics against hospital-associated MRSA. METHODOLOGY: A total of 103 MRSA clinical isolates recovered in two hospitals in Beijing were evaluated for susceptibility to SNH, oxacillin, cephalothin, meropenem, vancomycin, levofloxacin, minocycline, netilmicin, and trimethoprim/sulfamethoxazole by broth microdilution. Ten isolates were evaluated for potential for synergy between SNH and the antibiotics above by checkerboard assay. Time-kill analysis was performed in three isolates to characterize the kill kinetics of SNH alone and in combination with the antibiotics that engendered synergy in checkerboard assays. Besides, two reference strains were included in all assays. PRINCIPAL FINDINGS: SNH inhibited all test strains with minimum inhibitory concentrations (MICs) ranging from 16 to 64 µg/mL in susceptibility tests, and displayed inhibition to bacterial growth in concentration-dependent manner in time-kill analysis. In synergy studies, the combinations of SNH-oxacillin, SNH-cephalothin, SNH-meropenem and SNH-netilmicin showed synergistic effects against 12 MRSA strains with median fractional inhibitory concentration (FIC) indices of 0.38, 0.38, 0.25 and 0.38 in checkerboard assays. In time-kill analysis, SNH at 1/2 MIC in combination with oxacillin at 1/128 to 1/64 MIC or netilmicin at 1/8 to 1/2 MIC decreased the viable colonies by ≥2log(10) CFU/mL. CONCLUSIONS/SIGNIFICANCE: SNH demonstrated in vitro antibacterial activity against 103 hospital-associated MRSA isolates. Combinations of sub-MIC levels of SNH and oxacillin or netilmicin significantly improved the in vitro antibacterial activity against MRSA compared with either drug alone. The SNH-based combinations showed promise in combating MRSA.",2013 Jul 2,"['Lu, Xi', 'Yang, Xinyi', 'Li, Xue', 'Lu, Yun', 'Ren, Zhitao', 'Zhao, Longyin', 'Hu, Xinxin', 'Jiang, Jiandong', 'You, Xuefu']",PLoS One,,,False
e6a9266f1f45099b19b5c4f3a4cf62de41786e54,PMC,The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Does Not Replicate in Syrian Hamsters,http://dx.doi.org/10.1371/journal.pone.0069127,PMC3699510,23844250,CC0,"In 2012 a novel coronavirus, MERS-CoV, associated with severe respiratory disease emerged in the Arabian Peninsula. To date, 55 human cases have been reported, including 31 fatal cases. Several of the cases were likely a result of human-to-human transmission. The emergence of this novel coronavirus prompts the need for a small animal model to study the pathogenesis of this virus and to test the efficacy of potential intervention strategies. In this study we explored the use of Syrian hamsters as a small animal disease model, using intratracheal inoculation and inoculation via aerosol. Clinical signs of disease, virus replication, histological lesions, cytokine upregulation nor seroconversion were observed in any of the inoculated animals, indicating that MERS-CoV does not replicate in Syrian hamsters.",2013 Jul 2,"['de Wit, Emmie', 'Prescott, Joseph', 'Baseler, Laura', 'Bushmaker, Trenton', 'Thomas, Tina', 'Lackemeyer, Matthew G.', 'Martellaro, Cynthia', 'Milne-Price, Shauna', 'Haddock, Elaine', 'Haagmans, Bart L.', 'Feldmann, Heinz', 'Munster, Vincent J.']",PLoS One,,,True
3e03474356ba4414f631c94959e3c22e8e239c49,PMC,Real-Time Fluorescence Loop Mediated Isothermal Amplification for the Detection of Acinetobacter baumannii,http://dx.doi.org/10.1371/journal.pone.0066406,PMC3699609,23843955,CC BY,"BACKGROUND: Detection of Acinetobacter baumannii has been relying primarily on bacterial culture that often fails to return useful results in time. Although DNA-based assays are more sensitive than bacterial culture in detecting the pathogen, the molecular results are often inconsistent and challenged by doubts on false positives, such as those due to system- and environment-derived contaminations. In addition, these molecular tools require expensive laboratory instruments. Therefore, establishing molecular tools for field use require simpler molecular platforms. The loop-mediated isothermal amplification method is relatively simple and can be improved for better use in a routine clinical bacteriology laboratory. A simple and portable device capable of performing both the amplification and detection (by fluorescence) of LAMP in the same platform has been developed in recent years. This method is referred to as real-time loop-mediated isothermal amplification. In this study, we attempted to utilize this method for rapid detection of A. baumannii. METHODOLOGY AND SIGNIFICANT FINDINGS: Species-specific primers were designed to test the utility of this method. Clinical samples of A. baumannii were used to determine the sensitivity and specificity of this system compared to bacterial culture and a polymerase chain reaction method. All positive samples isolated from sputum were confirmed to be the species of Acinetobacter by 16S rRNA gene sequencing. The RealAmp method was found to be simpler and allowed real-time detection of DNA amplification, and could distinguish A. baumannii from Acinetobacter calcoaceticus and Acinetobacter genomic species 3. DNA was extracted by simple boiling method. Compared to bacterial culture, the sensitivity and specificity of RealAmp in detecting A. baumannii was 98.9% and 75.0%, respectively. CONCLUSION: The RealAmp assay only requires a single unit, and the assay positivity can be verified by visual inspection. Therefore, this assay has great potential of field use as a molecular tool for detection of A. baumannii.",2013 Jul 2,"['Wang, Qinqin', 'Zhou, Yanbin', 'Li, Shaoli', 'Zhuo, Chao', 'Xu, Siqi', 'Huang, Lixia', 'Yang, Ling', 'Liao, Kang']",PLoS One,,,True
59d9ebaa6d9c6c4e8a89c831e0cbe7036e884887,PMC,NEWS,http://dx.doi.org/10.7189/jogh.03.010201,PMC3700025,,CC BY,,2013 Jun,,J Glob Health,,,False
9c983db27cc8ff3e50008d8d2bc803e14da7d38b,PMC,Mice with different susceptibility to tick-borne encephalitis virus infection show selective neutralizing antibody response and inflammatory reaction in the central nervous system,http://dx.doi.org/10.1186/1742-2094-10-77,PMC3700758,23805778,CC BY,"BACKGROUND: The clinical course of tick-borne encephalitis (TBE), a disease caused by TBE virus, ranges from asymptomatic or mild influenza-like infection to severe debilitating encephalitis or encephalomyelitis. Despite the medical importance of this disease, some crucial steps in the development of encephalitis remain poorly understood. In particular, the basis of the disease severity is largely unknown. METHODS: TBE virus growth, neutralizing antibody response, key cytokine and chemokine mRNA production and changes in mRNA levels of cell surface markers of immunocompetent cells in brain were measured in mice with different susceptibilities to TBE virus infection. RESULTS: An animal model of TBE based on BALB/c-c-STS/A (CcS/Dem) recombinant congenic mouse strains showing different severities of the infection in relation to the host genetic background was developed. After subcutaneous inoculation of TBE virus, BALB/c mice showed medium susceptibility to the infection, STS mice were resistant, and CcS-11 mice were highly susceptible. The resistant STS mice showed lower and delayed viremia, lower virus production in the brain and low cytokine/chemokine mRNA production, but had a strong neutralizing antibody response. The most sensitive strain (CcS-11) failed in production of neutralizing antibodies, but exhibited strong cytokine/chemokine mRNA production in the brain. After intracerebral inoculation, all mouse strains were sensitive to the infection and had similar virus production in the brain, but STS mice survived significantly longer than CcS-11 mice. These two strains also differed in the expression of key cytokines/chemokines, particularly interferon gamma-induced protein 10 (IP-10/CXCL10) and monocyte chemotactic protein-1 (MCP-1/CCL2) in the brain. CONCLUSIONS: Our data indicate that the genetic control is an important factor influencing the clinical course of TBE. High neutralizing antibody response might be crucial for preventing host fatality, but high expression of various cytokines/chemokines during TBE can mediate immunopathology and be associated with more severe course of the infection and increased fatality.",2013 Jun 27,"['Palus, Martin', 'Vojtíšková, Jarmila', 'Salát, Jiří', 'Kopecký, Jan', 'Grubhoffer, Libor', 'Lipoldová, Marie', 'Demant, Peter', 'Růžek, Daniel']",J Neuroinflammation,,,True
0309a2f31c4344e9eecfedea296771452f62e8df,PMC,Mice with different susceptibility to tick-borne encephalitis virus infection show selective neutralizing antibody response and inflammatory reaction in the central nervous system,http://dx.doi.org/10.1186/1742-2094-10-77,PMC3700758,23805778,CC BY,"BACKGROUND: The clinical course of tick-borne encephalitis (TBE), a disease caused by TBE virus, ranges from asymptomatic or mild influenza-like infection to severe debilitating encephalitis or encephalomyelitis. Despite the medical importance of this disease, some crucial steps in the development of encephalitis remain poorly understood. In particular, the basis of the disease severity is largely unknown. METHODS: TBE virus growth, neutralizing antibody response, key cytokine and chemokine mRNA production and changes in mRNA levels of cell surface markers of immunocompetent cells in brain were measured in mice with different susceptibilities to TBE virus infection. RESULTS: An animal model of TBE based on BALB/c-c-STS/A (CcS/Dem) recombinant congenic mouse strains showing different severities of the infection in relation to the host genetic background was developed. After subcutaneous inoculation of TBE virus, BALB/c mice showed medium susceptibility to the infection, STS mice were resistant, and CcS-11 mice were highly susceptible. The resistant STS mice showed lower and delayed viremia, lower virus production in the brain and low cytokine/chemokine mRNA production, but had a strong neutralizing antibody response. The most sensitive strain (CcS-11) failed in production of neutralizing antibodies, but exhibited strong cytokine/chemokine mRNA production in the brain. After intracerebral inoculation, all mouse strains were sensitive to the infection and had similar virus production in the brain, but STS mice survived significantly longer than CcS-11 mice. These two strains also differed in the expression of key cytokines/chemokines, particularly interferon gamma-induced protein 10 (IP-10/CXCL10) and monocyte chemotactic protein-1 (MCP-1/CCL2) in the brain. CONCLUSIONS: Our data indicate that the genetic control is an important factor influencing the clinical course of TBE. High neutralizing antibody response might be crucial for preventing host fatality, but high expression of various cytokines/chemokines during TBE can mediate immunopathology and be associated with more severe course of the infection and increased fatality.",2013 Jun 27,"['Palus, Martin', 'Vojtíšková, Jarmila', 'Salát, Jiří', 'Kopecký, Jan', 'Grubhoffer, Libor', 'Lipoldová, Marie', 'Demant, Peter', 'Růžek, Daniel']",J Neuroinflammation,,,False
3380c2147c090bd81525c67d4200fb3860517008,PMC,Intranasally Administered Antigen 85B Gene Vaccine in Non-Replicating Human Parainfluenza Type 2 Virus Vector Ameliorates Mouse Atopic Dermatitis,http://dx.doi.org/10.1371/journal.pone.0066614,PMC3701015,23843958,CC BY,"Atopic dermatitis (AD) is a refractory and recurrent inflammatory skin disease. Various factors including heredity, environmental agent, innate and acquired immunity, and skin barrier function participate in the pathogenesis of AD. T -helper (Th) 2-dominant immunological milieu has been suggested in the acute phase of AD. Antigen 85B (Ag85B) is a 30-kDa secretory protein well conserved in Mycobacterium species. Ag85B has strong Th1-type cytokine inducing activity, and is expected to ameliorate Th2 condition in allergic disease. To perform Ag85B function in vivo, effective and less invasive vaccination method is required. Recently, we have established a novel functional virus vector; recombinant human parainfluenza type 2 virus vector (rhPIV2): highly expressive, replication-deficient, and very low-pathogenic vector. In this study, we investigated the efficacy of rhPIV2 engineered to express Ag85B (rhPIV2/Ag85B) in a mouse AD model induced by repeated oxazolone (OX) challenge. Ear swelling, dermal cell infiltrations and serum IgE level were significantly suppressed in the rhPIV2/Ag85B treated mouse group accompanied with elevated IFN-γ and IL-10 mRNA expressions, and suppressed IL-4, TNF-α and MIP-2 mRNA expressions. The treated mice showed no clinical symptom of croup or systemic adverse reactions. The respiratory tract epithelium captured rhPIV2 effectively without remarkable cytotoxic effects. These results suggested that rhPIV2/Ag85B might be a potent therapeutic tool to control allergic disorders.",2013 Jul 3,"['Kitagawa, Hiroshi', 'Kawano, Mitsuo', 'Yamanaka, Keiichi', 'Kakeda, Masato', 'Tsuda, Kenshiro', 'Inada, Hiroyasu', 'Yoneda, Misao', 'Sakaguchi, Tadashi', 'Nigi, Akina', 'Nishimura, Koumei', 'Komada, Hiroshi', 'Tsurudome, Masato', 'Yasutomi, Yasuhiro', 'Nosaka, Tetsuya', 'Mizutani, Hitoshi']",PLoS One,,,True
06ebe6e32a2e7241e23d3fb51c4dffeed389861d,PMC,Modelling the transmission of healthcare associated infections: a systematic review,http://dx.doi.org/10.1186/1471-2334-13-294,PMC3701468,23809195,CC BY,"BACKGROUND: Dynamic transmission models are increasingly being used to improve our understanding of the epidemiology of healthcare-associated infections (HCAI). However, there has been no recent comprehensive review of this emerging field. This paper summarises how mathematical models have informed the field of HCAI and how methods have developed over time. METHODS: MEDLINE, EMBASE, Scopus, CINAHL plus and Global Health databases were systematically searched for dynamic mathematical models of HCAI transmission and/or the dynamics of antimicrobial resistance in healthcare settings. RESULTS: In total, 96 papers met the eligibility criteria. The main research themes considered were evaluation of infection control effectiveness (64%), variability in transmission routes (7%), the impact of movement patterns between healthcare institutes (5%), the development of antimicrobial resistance (3%), and strain competitiveness or co-colonisation with different strains (3%). Methicillin-resistant Staphylococcus aureus was the most commonly modelled HCAI (34%), followed by vancomycin resistant enterococci (16%). Other common HCAIs, e.g. Clostridum difficile, were rarely investigated (3%). Very few models have been published on HCAI from low or middle-income countries. The first HCAI model has looked at antimicrobial resistance in hospital settings using compartmental deterministic approaches. Stochastic models (which include the role of chance in the transmission process) are becoming increasingly common. Model calibration (inference of unknown parameters by fitting models to data) and sensitivity analysis are comparatively uncommon, occurring in 35% and 36% of studies respectively, but their application is increasing. Only 5% of models compared their predictions to external data. CONCLUSIONS: Transmission models have been used to understand complex systems and to predict the impact of control policies. Methods have generally improved, with an increased use of stochastic models, and more advanced methods for formal model fitting and sensitivity analyses. Insights gained from these models could be broadened to a wider range of pathogens and settings. Improvements in the availability of data and statistical methods could enhance the predictive ability of models.",2013 Jun 28,"['van Kleef, Esther', 'Robotham, Julie V', 'Jit, Mark', 'Deeny, Sarah R', 'Edmunds, William J']",BMC Infect Dis,,,True
22e6bf7b64a17d055dca239d9fdac04edfb1414c,PMC,Emerging Infectious Diseases: Threats to Human Health and Global Stability,http://dx.doi.org/10.1371/journal.ppat.1003467,PMC3701702,23853589,CC0,,2013 Jul 4,"['Morens, David M.', 'Fauci, Anthony S.']",PLoS Pathog,,,True
cf4b53e86101ba9279f53b315f8aee6ecba9e0c0,PMC,"What we are watching—five top global infectious disease threats, 2012: a perspective from CDC’s Global Disease Detection Operations Center",http://dx.doi.org/10.3402/ehtj.v6i0.20632,PMC3701798,23827387,CC BY,"Disease outbreaks of international public health importance continue to occur regularly; detecting and tracking significant new public health threats in countries that cannot or might not report such events to the global health community is a challenge. The Centers for Disease Control and Prevention’s (CDC) Global Disease Detection (GDD) Operations Center, established in early 2007, monitors infectious and non-infectious public health events to identify new or unexplained global public health threats and better position CDC to respond, if public health assistance is requested or required. At any one time, the GDD Operations Center actively monitors approximately 30–40 such public health threats; here we provide our perspective on five of the top global infectious disease threats that we were watching in 2012: (1) avian influenza A (H5N1), (2) cholera, (3) wild poliovirus, (4) enterovirus-71, and (5) extensively drug-resistant tuberculosis.",2013 Jul 3,"['Christian, Kira A.', 'Ijaz, Kashef', 'Dowell, Scott F.', 'Chow, Catherine C.', 'Chitale, Rohit A.', 'Bresee, Joseph S.', 'Mintz, Eric', 'Pallansch, Mark A.', 'Wassilak, Steven', 'McCray, Eugene', 'Arthur, Ray R.']",Emerg Health Threats J,,,True
70945e1b77b2dd46582a7d73d30746432f209f0d,PMC,Alberta family physicians’ willingness to work during an influenza pandemic: a cross-sectional study,http://dx.doi.org/10.1186/1447-056X-12-3,PMC3702417,23800113,CC BY,"OBJECTIVE: Effective pandemic responses rely on frontline healthcare workers continuing to work despite increased risk to themselves. Our objective was to investigate Alberta family physicians willingness to work during an influenza pandemic. Design: Cross-sectional survey. Setting: Alberta prior to the fall wave of the H1N1 epidemic. Participants: 192 participants from a random sample of 1000 Alberta family physicians stratified by region. Main Outcome Measures: Willingness to work through difficult scenarios created by an influenza epidemic. RESULTS: The corrected response rate was 22%. The most physicians who responded were willing to continue working through some scenarios caused by a pandemic, but in other circumstances less than 50% would continue. Men were more willing to continue working than women. In some situations South African and British trained physicians were more willing to continue working than other groups. CONCLUSIONS: Although many physicians intend to maintain their practices in the event of a pandemic, in some circumstances fewer are willing to work. Pandemic preparation requires ensuring a workforce is available. Healthcare systems must provide frontline healthcare workers with the support and resources they need to enable them to continue providing care.",2013 Jun 26,"['Dickinson, James A', 'Bani-Adam, Gisoo', 'Williamson, Tyler', 'Berzins, Sandy', 'Pearce, Craig', 'Ricketson, Leah', 'Medd, Emily']",Asia Pac Fam Med,,,True
1e7e3df5deec55ed5c2fa7f9cba8854c6aeb7ab6,PMC,The incidence and aetiology of hospitalised community-acquired pneumonia among Vietnamese adults: a prospective surveillance in Central Vietnam,http://dx.doi.org/10.1186/1471-2334-13-296,PMC3702433,23815298,CC BY,"BACKGROUND: Lower respiratory tract infection (LRTI) including Community-acquired pneumonia (CAP) is a common infectious disease that is associated with significant morbidity and mortality. The patterns of aetiological pathogens differ by region and country. Special attention must be paid to CAP in Southeast Asia (SEA), a region facing rapid demographic transition. Estimates burden and aetiological patterns of CAP are essential for the clinical and public health management. The purposes of the study are to determine the incidence, aetiological pathogens, clinical pictures and risk factors of community-acquired pneumonia (CAP) in the Vietnamese adult population. METHODS: A prospective surveillance for hospitalised adult CAP was conducted in Khanh Hoa Province, Central Vietnam. All adults aged ≥15 years with lower respiratory tract infections (LRTI) admitted to a provincial hospital from September 2009 to August 2010 were enrolled in the study. Patients were classified into CAP and non-pneumonic LRTI (NPLRTI) according to the radiological findings. Bacterial pathogens were identified from sputum samples by the conventional culture and polymerase chain reaction (PCR) for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis; 13 respiratory viruses were identified from nasopharyngeal specimens by PCR. RESULTS: Of all 367 LRTI episodes examined, 174 (47%) were CAP. Older age, the presence of underlying respiratory conditions, and higher index score of smoking were associated with CAP. The one-year estimated incidence of hospitalised adult CAP in our study population was 0.81 per 1,000 person years. The incidence increased considerably with age and was highest among the elderly. The case fatality proportion of hospitalised CAP patients was 9.8%. Among 286 sputum samples tested for bacterial PCR, 79 (28%) were positive for H. influenzae, and 65 (23%) were positive for S. pneumoniae. Among 357 samples tested for viral PCR, 73 (21%) were positive for respiratory viruses; influenza A (n = 32, 9%) was the most common. CONCLUSIONS: The current adult CAP incidence in Vietnam was relatively low; this result was mainly attributed to the young age of our study population.",2013 Jul 1,"['Takahashi, Kensuke', 'Suzuki, Motoi', 'Minh, Le Nhat', 'Anh, Nguyen Hien', 'Huong, Luu Thi Minh', 'Son, Tran Vo Vinh', 'Long, Phan The', 'Ai, Nguyen Thi Thuy', 'Tho, Le Huu', 'Morimoto, Konosuke', 'Kilgore, Paul E', 'Anh, Dang Duc', 'Ariyoshi, Koya', 'Yoshida, Lay Myint']",BMC Infect Dis,,,True
ae29a35ad6b9e4267e1d965b523a6b72cb2c088c,PMC,Major Histocompatibility Complex Class I Haplotype Diversity in Chinese Rhesus Macaques,http://dx.doi.org/10.1534/g3.113.006254,PMC3704247,23696100,CC BY,"The use of Chinese-origin rhesus macaques (Macaca mulatta) for infectious disease immunity research is increasing despite the relative lack of major histocompatibility complex (MHC) class I immunogenetics information available for this population. We determined transcript-based MHC class I haplotypes for 385 Chinese rhesus macaques from five different experimental cohorts, providing a concise representation of the full complement of MHC class I major alleles expressed by each animal. In total, 123 Mamu-A and Mamu-B haplotypes were defined in the full Chinese rhesus macaque cohort. We then performed an analysis of haplotype frequencies across the experimental cohorts of Chinese rhesus macaques, as well as a comparison against a group of 96 Indian rhesus macaques. Notably, 35 of the 51 Mamu-A and Mamu-B haplotypes observed in Indian rhesus macaques were also detected in the Chinese population, with 85% of the 385 Chinese-origin rhesus macaques expressing at least one of these class I haplotypes. This unexpected conservation of Indian rhesus macaque MHC class I haplotypes in the Chinese rhesus macaque population suggests that immunologic insights originally gleaned from studies using Indian rhesus macaques may be more applicable to Chinese rhesus macaques than previously appreciated and may provide an opportunity for studies of CD8(+) T-cell responses between populations. It may also be possible to extend these studies across multiple species of macaques, as we found evidence of shared ancestral haplotypes between Chinese rhesus and Mauritian cynomolgus macaques.",2013 Jul 1,"['Karl, Julie A.', 'Bohn, Patrick S.', 'Wiseman, Roger W.', 'Nimityongskul, Francesca A.', 'Lank, Simon M.', 'Starrett, Gabriel J.', 'O’Connor, David H.']",G3 (Bethesda),,,True
9043919dae5100888c661ef0c5c24d144fdf4351,PMC,Major Histocompatibility Complex Class I Haplotype Diversity in Chinese Rhesus Macaques,http://dx.doi.org/10.1534/g3.113.006254,PMC3704247,23696100,CC BY,"The use of Chinese-origin rhesus macaques (Macaca mulatta) for infectious disease immunity research is increasing despite the relative lack of major histocompatibility complex (MHC) class I immunogenetics information available for this population. We determined transcript-based MHC class I haplotypes for 385 Chinese rhesus macaques from five different experimental cohorts, providing a concise representation of the full complement of MHC class I major alleles expressed by each animal. In total, 123 Mamu-A and Mamu-B haplotypes were defined in the full Chinese rhesus macaque cohort. We then performed an analysis of haplotype frequencies across the experimental cohorts of Chinese rhesus macaques, as well as a comparison against a group of 96 Indian rhesus macaques. Notably, 35 of the 51 Mamu-A and Mamu-B haplotypes observed in Indian rhesus macaques were also detected in the Chinese population, with 85% of the 385 Chinese-origin rhesus macaques expressing at least one of these class I haplotypes. This unexpected conservation of Indian rhesus macaque MHC class I haplotypes in the Chinese rhesus macaque population suggests that immunologic insights originally gleaned from studies using Indian rhesus macaques may be more applicable to Chinese rhesus macaques than previously appreciated and may provide an opportunity for studies of CD8(+) T-cell responses between populations. It may also be possible to extend these studies across multiple species of macaques, as we found evidence of shared ancestral haplotypes between Chinese rhesus and Mauritian cynomolgus macaques.",2013 Jul 1,"['Karl, Julie A.', 'Bohn, Patrick S.', 'Wiseman, Roger W.', 'Nimityongskul, Francesca A.', 'Lank, Simon M.', 'Starrett, Gabriel J.', 'O’Connor, David H.']",G3 (Bethesda),,,False
d9b1b94a99f1843613b257218f8b5af4fcb2d38c,PMC,Major Histocompatibility Complex Class I Haplotype Diversity in Chinese Rhesus Macaques,http://dx.doi.org/10.1534/g3.113.006254,PMC3704247,23696100,CC BY,"The use of Chinese-origin rhesus macaques (Macaca mulatta) for infectious disease immunity research is increasing despite the relative lack of major histocompatibility complex (MHC) class I immunogenetics information available for this population. We determined transcript-based MHC class I haplotypes for 385 Chinese rhesus macaques from five different experimental cohorts, providing a concise representation of the full complement of MHC class I major alleles expressed by each animal. In total, 123 Mamu-A and Mamu-B haplotypes were defined in the full Chinese rhesus macaque cohort. We then performed an analysis of haplotype frequencies across the experimental cohorts of Chinese rhesus macaques, as well as a comparison against a group of 96 Indian rhesus macaques. Notably, 35 of the 51 Mamu-A and Mamu-B haplotypes observed in Indian rhesus macaques were also detected in the Chinese population, with 85% of the 385 Chinese-origin rhesus macaques expressing at least one of these class I haplotypes. This unexpected conservation of Indian rhesus macaque MHC class I haplotypes in the Chinese rhesus macaque population suggests that immunologic insights originally gleaned from studies using Indian rhesus macaques may be more applicable to Chinese rhesus macaques than previously appreciated and may provide an opportunity for studies of CD8(+) T-cell responses between populations. It may also be possible to extend these studies across multiple species of macaques, as we found evidence of shared ancestral haplotypes between Chinese rhesus and Mauritian cynomolgus macaques.",2013 Jul 1,"['Karl, Julie A.', 'Bohn, Patrick S.', 'Wiseman, Roger W.', 'Nimityongskul, Francesca A.', 'Lank, Simon M.', 'Starrett, Gabriel J.', 'O’Connor, David H.']",G3 (Bethesda),,,False
9c3004ec902e954fcf2cb0b8a906cc7e8394ec79,PMC,Major Histocompatibility Complex Class I Haplotype Diversity in Chinese Rhesus Macaques,http://dx.doi.org/10.1534/g3.113.006254,PMC3704247,23696100,CC BY,"The use of Chinese-origin rhesus macaques (Macaca mulatta) for infectious disease immunity research is increasing despite the relative lack of major histocompatibility complex (MHC) class I immunogenetics information available for this population. We determined transcript-based MHC class I haplotypes for 385 Chinese rhesus macaques from five different experimental cohorts, providing a concise representation of the full complement of MHC class I major alleles expressed by each animal. In total, 123 Mamu-A and Mamu-B haplotypes were defined in the full Chinese rhesus macaque cohort. We then performed an analysis of haplotype frequencies across the experimental cohorts of Chinese rhesus macaques, as well as a comparison against a group of 96 Indian rhesus macaques. Notably, 35 of the 51 Mamu-A and Mamu-B haplotypes observed in Indian rhesus macaques were also detected in the Chinese population, with 85% of the 385 Chinese-origin rhesus macaques expressing at least one of these class I haplotypes. This unexpected conservation of Indian rhesus macaque MHC class I haplotypes in the Chinese rhesus macaque population suggests that immunologic insights originally gleaned from studies using Indian rhesus macaques may be more applicable to Chinese rhesus macaques than previously appreciated and may provide an opportunity for studies of CD8(+) T-cell responses between populations. It may also be possible to extend these studies across multiple species of macaques, as we found evidence of shared ancestral haplotypes between Chinese rhesus and Mauritian cynomolgus macaques.",2013 Jul 1,"['Karl, Julie A.', 'Bohn, Patrick S.', 'Wiseman, Roger W.', 'Nimityongskul, Francesca A.', 'Lank, Simon M.', 'Starrett, Gabriel J.', 'O’Connor, David H.']",G3 (Bethesda),,,False
98c2af7070735431908c6d271df6b49f01924f96,PMC,Antiviral Type I and Type III Interferon Responses in the Central Nervous System,http://dx.doi.org/10.3390/v5030834,PMC3705299,23503326,CC BY,"The central nervous system (CNS) harbors highly differentiated cells, such as neurons that are essential to coordinate the functions of complex organisms. This organ is partly protected by the blood-brain barrier (BBB) from toxic substances and pathogens carried in the bloodstream. Yet, neurotropic viruses can reach the CNS either by crossing the BBB after viremia, or by exploiting motile infected cells as Trojan horses, or by using axonal transport. Type I and type III interferons (IFNs) are cytokines that are critical to control early steps of viral infections. Deficiencies in the IFN pathway have been associated with fatal viral encephalitis both in humans and mice. Therefore, the IFN system provides an essential protection of the CNS against viral infections. Yet, basal activity of the IFN system appears to be low within the CNS, likely owing to the toxicity of IFN to this organ. Moreover, after viral infection, neurons and oligodendrocytes were reported to be relatively poor IFN producers and appear to keep some susceptibility to neurotropic viruses, even in the presence of IFN. This review addresses some trends and recent developments concerning the role of type I and type III IFNs in: i) preventing neuroinvasion and infection of CNS cells; ii) the identity of IFN-producing cells in the CNS; iii) the antiviral activity of ISGs; and iv) the activity of viral proteins of neurotropic viruses that target the IFN pathway.",2013 Mar 15,"['Sorgeloos, Frédéric', 'Kreit, Marguerite', 'Hermant, Pascale', 'Lardinois, Cécile', 'Michiels, Thomas']",Viruses,,,True
e4281a03ae26dbf7a445f1697dde5b4352fec07b,PMC,"Baicalein, Ethyl Acetate, and Chloroform Extracts of Scutellaria baicalensis Inhibit the Neuraminidase Activity of Pandemic 2009 H1N1 and Seasonal Influenza A Viruses",http://dx.doi.org/10.1155/2013/750803,PMC3705751,23864896,CC BY,"This study rated antiviral activity of Scutellaria baicalensis Georgi (S. baicalensis) extracts against influenza A virus subtypes, for example, pandemic 2009 H1N1, seasonal H1N1 and H3N2. Ethyl acetate (EtOAc) and chloroform extracts inhibited in vitro neuraminidase (NA) enzymatic activity and viral replication more than methanol (MeOH) extract. EtOAc extract demonstrated NA inhibition IC(50) values ranging from 73.16 to 487.40 μg/mL and plaque reduction IC(50) values ranging from 23.7 to 27.4 μg/mL. Chloroform extract showed antiviral activities with plaque reduction IC(50) values ranging from 14.16 to 41.49 μg/mL Time-of-addition assay indicated that EtOAc and chloroform extracts also significantly inhibited virus yields after infection. HPLC analysis demonstrated that baicalin was dominant in the MeOH extract; baicalein and chrysin were rich in the EtOAc and chloroform extracts. Molecular simulation revealed baicalein hydrogen bonding with Glu277 as well as hydrophobic and Van der Waals interactions with Ile222, Arg224, Ser246, and Tyr347 in NA1 active sites of NA1. Baicalein inhibited in vitro replication of influenza A viruses pandemic 2009 H1N1 (IC(50) = 0.018 μM) and seasonal 2007 H1N1 using plaque reduction assays. A combination of low-dose baicalein with other anti-influenza agents could be applicable for development of alternative remedies treating influenza A virus infection.",2013 Jun 20,"['Hour, Mann-Jen', 'Huang, Su-Hua', 'Chang, Ching-Yao', 'Lin, Yen-Kuan', 'Wang, Ching-Ying', 'Chang, Yuan-Shiun', 'Lin, Cheng-Wen']",Evid Based Complement Alternat Med,,,True
d540410f675824bd89408b309c4502279483cbe3,PMC,Microglia Play a Major Role in Direct Viral-Induced Demyelination,http://dx.doi.org/10.1155/2013/510396,PMC3705805,23864878,CC BY,"Microglia are the resident macrophage-like populations in the central nervous system (CNS). Microglia remain quiescent, unable to perform effector and antigen presentation (APC) functions until activated by injury or infection, and have been suggested to represent the first line of defence for the CNS. Previous studies demonstrated that microglia can be persistently infected by neurotropic mouse hepatitis virus (MHV) which causes meningoencephalitis, myelitis with subsequent axonal loss, and demyelination and serve as a virus-induced model of human neurological disease multiple sclerosis (MS). Current studies revealed that MHV infection is associated with the pronounced activation of microglia during acute inflammation, as evidenced by characteristic changes in cellular morphology and increased expression of microglia-specific proteins, Iba1 (ionized calcium-binding adaptor molecule 1), which is a macrophage/microglia-specific novel calcium-binding protein and involved in membrane ruffling and phagocytosis. During chronic inflammation (day 30 postinfection), microglia were still present within areas of demyelination. Experiments performed in ex vivo spinal cord slice culture and in vitro neonatal microglial culture confirmed direct microglial infection. Our results suggest that MHV can directly infect and activate microglia during acute inflammation, which in turn during chronic inflammation stage causes phagocytosis of myelin sheath leading to chronic inflammatory demyelination.",2013 Jun 20,"['Chatterjee, Dhriti', 'Biswas, Kaushiki', 'Nag, Soma', 'Ramachandra, S. G.', 'Das Sarma, Jayasri']",Clin Dev Immunol,,,False
45ceff2a130c98717dcd6984a2fec10e86575c91,PMC,Microglia Play a Major Role in Direct Viral-Induced Demyelination,http://dx.doi.org/10.1155/2013/510396,PMC3705805,23864878,CC BY,"Microglia are the resident macrophage-like populations in the central nervous system (CNS). Microglia remain quiescent, unable to perform effector and antigen presentation (APC) functions until activated by injury or infection, and have been suggested to represent the first line of defence for the CNS. Previous studies demonstrated that microglia can be persistently infected by neurotropic mouse hepatitis virus (MHV) which causes meningoencephalitis, myelitis with subsequent axonal loss, and demyelination and serve as a virus-induced model of human neurological disease multiple sclerosis (MS). Current studies revealed that MHV infection is associated with the pronounced activation of microglia during acute inflammation, as evidenced by characteristic changes in cellular morphology and increased expression of microglia-specific proteins, Iba1 (ionized calcium-binding adaptor molecule 1), which is a macrophage/microglia-specific novel calcium-binding protein and involved in membrane ruffling and phagocytosis. During chronic inflammation (day 30 postinfection), microglia were still present within areas of demyelination. Experiments performed in ex vivo spinal cord slice culture and in vitro neonatal microglial culture confirmed direct microglial infection. Our results suggest that MHV can directly infect and activate microglia during acute inflammation, which in turn during chronic inflammation stage causes phagocytosis of myelin sheath leading to chronic inflammatory demyelination.",2013 Jun 20,"['Chatterjee, Dhriti', 'Biswas, Kaushiki', 'Nag, Soma', 'Ramachandra, S. G.', 'Das Sarma, Jayasri']",Clin Dev Immunol,,,False
7107f088cbed45d8a06a026276ccf4d602d50f10,PMC,Microglia Play a Major Role in Direct Viral-Induced Demyelination,http://dx.doi.org/10.1155/2013/510396,PMC3705805,23864878,CC BY,"Microglia are the resident macrophage-like populations in the central nervous system (CNS). Microglia remain quiescent, unable to perform effector and antigen presentation (APC) functions until activated by injury or infection, and have been suggested to represent the first line of defence for the CNS. Previous studies demonstrated that microglia can be persistently infected by neurotropic mouse hepatitis virus (MHV) which causes meningoencephalitis, myelitis with subsequent axonal loss, and demyelination and serve as a virus-induced model of human neurological disease multiple sclerosis (MS). Current studies revealed that MHV infection is associated with the pronounced activation of microglia during acute inflammation, as evidenced by characteristic changes in cellular morphology and increased expression of microglia-specific proteins, Iba1 (ionized calcium-binding adaptor molecule 1), which is a macrophage/microglia-specific novel calcium-binding protein and involved in membrane ruffling and phagocytosis. During chronic inflammation (day 30 postinfection), microglia were still present within areas of demyelination. Experiments performed in ex vivo spinal cord slice culture and in vitro neonatal microglial culture confirmed direct microglial infection. Our results suggest that MHV can directly infect and activate microglia during acute inflammation, which in turn during chronic inflammation stage causes phagocytosis of myelin sheath leading to chronic inflammatory demyelination.",2013 Jun 20,"['Chatterjee, Dhriti', 'Biswas, Kaushiki', 'Nag, Soma', 'Ramachandra, S. G.', 'Das Sarma, Jayasri']",Clin Dev Immunol,,,True
25d8592c8527ce05463209c6e0c3f61c75b65f86,PMC,"Febrile neutropenia: significance of elaborated screening for respiratory viruses, and the comparison of different sampling methods, in neutropenic patients with hematological malignancies",http://dx.doi.org/10.1186/1743-422X-10-212,PMC3706282,23805898,CC BY,"BACKGROUND: During febrile neutropenia in only 30 to 60 percent an infectious agent is identified. This diagnostic gap could hypothetically be reduced with the broad implementation of molecular detection techniques like PCR, which has revolutionized the detection of infectious diseases during the last two decades. FINDINGS: We performed a longitudinal prospective study (N = 81) of neutropenic patients to assess the role of respiratory viruses in neutropenic fever and to determine the clinical relevance of blind screening for these viruses. Respiratory viruses were recovered in 14% of the patients prior to neutropenia. In 13% of neutropenic patients without fever and in 19% of those with fever, a respiratory virus was detected. Comparing different sample types; nasal swabs performed significantly better (16/117 = 43%), than throat swabs (6/106 = 6%). Throat gurgles did not show significant differences from the latter sample types. CONCLUSIONS: Blind diagnostic screening for respiratory viruses before or during neutropenia is not useful. Nasal swabs are sensitive and practical option for screening on respiratory viruses.",2013 Jun 27,"['Jansen, Rogier R', 'Biemond, Bart J', 'Schinkel, Janke', 'Koekkoek, Sylvie M', 'Molenkamp, Richard', 'de Jong, Menno D', 'Visser, Caroline E']",Virol J,,,True
b454887997af026ed0589fcb18e59aed44473e1d,PMC,Super Resolution Microscopy Reveals that Caveolin-1 Is Required for Spatial Organization of CRFB1 and Subsequent Antiviral Signaling in Zebrafish,http://dx.doi.org/10.1371/journal.pone.0068759,PMC3706321,23874753,CC BY,"Understanding spatial distribution and dynamics of receptors within unperturbed membranes is essential for elucidating their role in antiviral signaling, but conventional studies of detergent-resistant membrane fractions cannot provide this information. Caveolae are integral to numerous signaling pathways and these membrane domains have been previously implicated in viral entry but not antiviral defense. This study shows, for the first time, the importance of spatio-temporal regulation of signaling receptors and the importance of the regulation of clustering for downstream signaling. A novel mechanism for virus evasion of host cell defenses is demonstrated through disruption of clusters of signaling molecules organized within caveolin-rich domains. Viral infection leads to a downregulation in Caveolin-1b (Cav-1b), disrupting clusters of CRFB1, a zebrafish type I interferon receptor (–R) subunit. Super-resolution microscopy has enabled the first single-molecule imaging of CRFB1 association with cav-1b-containing membrane domains. Strikingly, downregulation of Cav-1b, the major protein component of caveolae, caused CRFB1 clusters to disperse. Dispersal of CRFB1 clusters led to a suppressed antiviral immune response both in vitro and in vivo, through abrogation of downstream signaling. This response strongly suggests that CRFB1 organization within cav-1b-containing membrane domains is critical for IFN-mediated antiviral defense and presents a previously undescribed antiviral evasion strategy to alter IFN signaling and the antiviral immune response.",2013 Jul 9,"['Gabor, Kristin A.', 'Stevens, Chad R.', 'Pietraszewski, Matthew J.', 'Gould, Travis J.', 'Shim, Juyoung', 'Yoder, Jeffrey A.', 'Lam, Siew Hong', 'Gong, Zhiyuan', 'Hess, Samuel T.', 'Kim, Carol H.']",PLoS One,,,True
4c7ae8ea3cf737fe457b191ae7a7dc2fcaee44bf,PMC,Hepatitis C Virus Non-Structural Protein 3 Interacts with Cytosolic 5′(3′)-Deoxyribonucleotidase and Partially Inhibits Its Activity,http://dx.doi.org/10.1371/journal.pone.0068736,PMC3706368,23874742,CC BY,"Infection with hepatitis C virus (HCV) is etiologically involved in liver cirrhosis, hepatocellular carcinoma and B-cell lymphomas. It has been demonstrated previously that HCV non-structural protein 3 (NS3) is involved in cell transformation. In this study, a yeast two-hybrid screening experiment was conducted to identify cellular proteins interacting with HCV NS3 protein. Cytosolic 5′(3′)-deoxyribonucleotidase (cdN, dNT-1) was found to interact with HCV NS3 protein. Binding domains of HCV NS3 and cellular cdN proteins were also determined using the yeast two-hybrid system. Interactions between HCV NS3 and cdN proteins were further demonstrated by co-immunoprecipitation and confocal analysis in cultured cells. The cellular cdN activity was partially repressed by NS3 protein in both the transiently-transfected and the stably-transfected systems. Furthermore, HCV partially repressed the cdN activity while had no effect on its protein expression in the systems of HCV sub-genomic replicons and infectious HCV virions. Deoxyribonucleotidases are present in most mammalian cells and involve in the regulation of intracellular deoxyribonucleotides pools by substrate cycles. Control of DNA precursor concentration is essential for the maintenance of genetic stability. Reduction of cdN activity would result in the imbalance of DNA precursor concentrations. Thus, our results suggested that HCV partially reduced the cdN activity via its NS3 protein and this may in turn cause diseases.",2013 Jul 9,"['Fang, Chiu-Ping', 'Li, Zhi-Cheng', 'Yang, Chee-Hing', 'Cheng, Ju-Chien', 'Yeh, Yung-Ju', 'Sun, Tsai-Hsia', 'Li, Hui-Chun', 'Juang, Yue-Li', 'Lo, Shih-Yen']",PLoS One,,,True
235451b60cac00666f0e69e9d196d090da8609a5,PMC,Effects of Nasal or Pulmonary Delivered Treatments with an Adenovirus Vectored Interferon (mDEF201) on Respiratory and Systemic Infections in Mice Caused by Cowpox and Vaccinia Viruses,http://dx.doi.org/10.1371/journal.pone.0068685,PMC3706414,23874722,CC BY,"An adenovirus 5 vector encoding for mouse interferon alpha, subtype 5 (mDEF201) was evaluated for efficacy against lethal cowpox (Brighton strain) and vaccinia (WR strain) virus respiratory and systemic infections in mice. Two routes of mDEF201 administration were used, nasal sinus (5-µl) and pulmonary (50-µl), to compare differences in efficacy, since the preferred treatment of humans would be in a relatively small volume delivered intranasally. Lower respiratory infections (LRI), upper respiratory infections (URI), and systemic infections were induced by 50-µl intranasal, 10-µl intranasal, and 100-µl intraperitoneal virus challenges, respectively. mDEF201 treatments were given prophylactically either 24 h (short term) or 56d (long-term) prior to virus challenge. Single nasal sinus treatments of 10(6) and 10(7) PFU/mouse of mDEF201 protected all mice from vaccinia-induced LRI mortality (comparable to published studies with pulmonary delivered mDEF201). Systemic vaccinia infections responded significantly better to nasal sinus delivered mDEF201 than to pulmonary treatments. Cowpox LRI infections responded to 10(7) mDEF201 treatments, but a 10(6) dose was only weakly protective. Cowpox URI infections were equally treatable by nasal sinus and pulmonary delivered mDEF201 at 10(7) PFU/mouse. Dose-responsive prophylaxis with mDEF201, given one time only 56 d prior to initiating a vaccinia virus LRI infection, was 100% protective from 10(5) to 10(7) PFU/mouse. Improvements in lung hemorrhage score and lung weight were evident, as were decreases in liver, lung, and spleen virus titers. Thus, mDEF201 was able to treat different vaccinia and cowpox virus infections using both nasal sinus and pulmonary treatment regimens, supporting its development for humans.",2013 Jul 9,"['Smee, Donald F.', 'Wong, Min-Hui', 'Hurst, Brett L.', 'Ennis, Jane', 'Turner, Jeffrey D.']",PLoS One,,,True
7862ffdcf951e5860a7e3dc66c9d3b07f5fbc281,PMC,A Functional Promoter Polymorphism of IFITM3 Is Associated with Susceptibility to Pediatric Tuberculosis in Han Chinese Population,http://dx.doi.org/10.1371/journal.pone.0067816,PMC3706438,23874452,CC BY,"A susceptibility locus for tuberculosis, a re-emerging infectious disease throughout the world, was previously discovered to exist on chromosome 11p15. IFITM3 gene encoding for interferon inducible transmembrane protein 3, is located at 11p15. It acts as an effector molecule for interferon-gamma, which is essential for anti-tuberculosis immune response. In order to investigate the association between susceptibility to TB and genetic polymorphisms of the IFITM3 core promoter, a case-control study including 368 TB patients and 794 healthy controls was performed in Han Chinese children in northern China. The rs3888188 polymorphism showed significant association with susceptibility to TB. The rs3888188 G allele, acting recessively, was more frequent in TB patients (95% confidence interval: 1.08–1.56, Bonferroni P-value: 0.039). We further assessed the effect of rs3888188 polymorphism on IFITM3 transcription in vitro. As based on luciferase promoter assays, the promoter activity of haplotypes with rs3888188 G allele was lower than that of haplotypes with rs3888188 T allele. Moreover, peripheral-blood mononuclear cells carrying rs3888188 GG genotype showed a reduced IFITM3 mRNA level compared to cells carrying TT or GT genotype. In conclusion, rs3888188, a functional promoter polymorphism of IFITM3, was identified to influence the risk for pediatric TB in Han Chinese population.",2013 Jul 9,"['Shen, Chen', 'Wu, Xi-rong', 'Jiao, Wei-wei', 'Sun, Lin', 'Feng, Wei-xing', 'Xiao, Jing', 'Miao, Qing', 'Liu, Fang', 'Yin, Qing-qin', 'Zhang, Chen-guang', 'Guo, Ya-jie', 'Shen, A-dong']",PLoS One,,,True
b6682adfe5026c78e3d59b165126abfa8945eb5f,PMC,Dendritic Cell Immunoreceptor Is a New Target for Anti-AIDS Drug Development: Identification of DCIR/HIV-1 Inhibitors,http://dx.doi.org/10.1371/journal.pone.0067873,PMC3706466,23874461,CC BY,"The HIV-1 pandemic continues to expand while no effective vaccine or cure is yet available. Existing therapies have managed to limit mortality and control viral proliferation, but are associated with side effects, do not cure the disease and are subject to development of resistance. Finding new therapeutic targets and drugs is therefore crucial. We have previously shown that the dendritic cell immunoreceptor (DCIR), a C-type lectin receptor expressed on dendritic cells (DCs), acts as an attachment factor for HIV-1 to DCs and contributes to HIV-1 transmission to CD4(+) T lymphocytes (CD4TL). Directly involved in HIV-1 infection, DCIR is expressed in apoptotic or infected CD4TL and promotes trans-infection to bystander cells. Here we report the 3D modelling of the extracellular domain of DCIR. Based on this structure, two surface accessible pockets containing the carbohydrate recognition domain and the EPS binding motif, respectively, were targeted for screening of chemicals that will disrupt normal interaction with HIV-1 particle. Preliminary screening using Raji-CD4-DCIR cells allowed identification of two inhibitors that decreased HIV-1 attachment and propagation. The impact of these inhibitors on infection of DCs and CD4TL was evaluated as well. The results of this study thus identify novel molecules capable of blocking HIV-1 transmission by DCs and CD4TL.",2013 Jul 9,"['Lambert, Alexandra A.', 'Azzi, Arezki', 'Lin, Sheng-Xiang', 'Allaire, Geneviève', 'St-Gelais, Karianne P.', 'Tremblay, Michel J.', 'Gilbert, Caroline']",PLoS One,,,True
19d93173c328e9ca42bd4238ccb39aa8da818422,PMC,An exploration of social and economic outcome and associated health-related quality of life after critical illness in general intensive care unit survivors: a 12-month follow-up study,http://dx.doi.org/10.1186/cc12745,PMC3706775,23714692,CC BY,"INTRODUCTION: The socio-economic impact of critical illnesses on patients and their families in Europe has yet to be determined. The aim of this exploratory study was to estimate changes in family circumstances, social and economic stability, care requirements and access to health services for patients during their first 12 months after ICU discharge. METHODS: Multi-center questionnaire-based study of survivors of critical illness at 6 and 12 months after ICU discharge. RESULTS: Data for 293 consenting patients who spent greater than 48 hours in one of 22 UK ICUs were obtained at 6 and 12 months post-ICU discharge. There was little evidence of a change in accommodation or relationship status between pre-admission and 12 months following discharge from an ICU. A negative impact on family income was reported by 33% of all patients at 6 months and 28% at 12 months. There was nearly a 50% reduction in the number of patients who reported employment as their sole source of income at 12 months (19% to 11%) compared with pre-admission. One quarter of patients reported themselves in need of care assistance at 6 months and 22% at 12 months. The majority of care was provided by family members (80% and 78%, respectively), for half of whom there was a negative impact on employment. Amongst all patients receiving care, 26% reported requiring greater than 50 hours a week. Following discharge, 79% of patients reported attending their primary care physician and 44% had seen a community nurse. Mobility problems nearly doubled between pre-admission and 6 months (32% to 64%). Furthermore, 73% reported moderate or severe pain at 12 months and 44% remained significantly anxious or depressed. CONCLUSIONS: Survivors of critical illness in the UK face a negative impact on employment and commonly have a care requirement after discharge from hospital. This has a corresponding negative impact on family income. The majority of the care required is provided by family members. This effect was apparent by 6 months and had not materially improved by 12 months. This exploratory study has identified the potential for a significant socio-economic burden following critical illness.",2013 May 28,"['Griffiths, John', 'Hatch, Robert A', 'Bishop, Judith', 'Morgan, Kayleigh', 'Jenkinson, Crispin', 'Cuthbertson, Brian H', 'Brett, Stephen J']",Crit Care,,,True
2f9d66c86c6ef08d8e3679e2cd01c2b140e68a32,PMC,A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris,http://dx.doi.org/10.1371/journal.pone.0070190,PMC3707868,23875020,CC BY,"State-of-the-art monoclonal antibody (mAb) discovery methods that utilize surface display techniques in prokaryotic and eukaryotic cells require multiple steps of reformatting and switching of hosts to transition from display to expression. This results in a separation between antibody affinity maturation and full-length mAb production platforms. Here, we report for the first time, a method in Glyco-engineered Pichia pastoris that enables simultaneous surface display and secretion of full-length mAb molecules with human-like N-glycans using the same yeast cell. This paradigm takes advantage of homo-dimerization of the Fc portion of an IgG molecule to a surface-anchored ""bait"" Fc, which results in targeting functional “half” IgGs to the cell wall of Pichia pastoris without interfering with the secretion of full length mAb. We show the utility of this method in isolating high affinity, well-expressed anti-PCSK9 leads from a designed library that was created by mating yeasts containing either light chain or heavy chain IgG libraries. Coupled with Glyco-engineered Pichia pastoris , this method provides a powerful tool for the discovery and production of therapeutic human mAbs in the same host thus improving drug developability and potentially shortening the discovery time cycle.",2013 Jul 10,"['Shaheen, Hussam H.', 'Prinz, Bianka', 'Chen, Ming-Tang', 'Pavoor, Tej', 'Lin, Song', 'Houston-Cummings, Nga Rewa', 'Moore, Renee', 'Stadheim, Terrance A.', 'Zha, Dongxing']",PLoS One,,,True
8a2b2c72af5a57c21d912a3f1e543bcd75345883,PMC,Application of next-generation sequencing technologies in virology,http://dx.doi.org/10.1099/vir.0.043182-0,PMC3709572,22647373,CC BY,"The progress of science is punctuated by the advent of revolutionary technologies that provide new ways and scales to formulate scientific questions and advance knowledge. Following on from electron microscopy, cell culture and PCR, next-generation sequencing is one of these methodologies that is now changing the way that we understand viruses, particularly in the areas of genome sequencing, evolution, ecology, discovery and transcriptomics. Possibilities for these methodologies are only limited by our scientific imagination and, to some extent, by their cost, which has restricted their use to relatively small numbers of samples. Challenges remain, including the storage and analysis of the large amounts of data generated. As the chemistries employed mature, costs will decrease. In addition, improved methods for analysis will become available, opening yet further applications in virology including routine diagnostic work on individuals, and new understanding of the interaction between viral and host transcriptomes. An exciting era of viral exploration has begun, and will set us new challenges to understand the role of newly discovered viral diversity in both disease and health.",2012 Sep,"['Radford, Alan D.', 'Chapman, David', 'Dixon, Linda', 'Chantrey, Julian', 'Darby, Alistair C.', 'Hall, Neil']",J Gen Virol,,,True
d4c0c411fdb8d2389288d0389cf02121ae6d8a9c,PMC,"Comprehensive analysis of the HEPN superfamily: identification of novel roles in intra-genomic conflicts, defense, pathogenesis and RNA processing",http://dx.doi.org/10.1186/1745-6150-8-15,PMC3710099,23768067,CC BY,"BACKGROUND: The major role of enzymatic toxins that target nucleic acids in biological conflicts at all levels has become increasingly apparent thanks in large part to the advances of comparative genomics. Typically, toxins evolve rapidly hampering the identification of these proteins by sequence analysis. Here we analyze an unexpectedly widespread superfamily of toxin domains most of which possess RNase activity. RESULTS: The HEPN superfamily is comprised of all α-helical domains that were first identified as being associated with DNA polymerase β-type nucleotidyltransferases in prokaryotes and animal Sacsin proteins. Using sensitive sequence and structure comparison methods, we vastly extend the HEPN superfamily by identifying numerous novel families and by detecting diverged HEPN domains in several known protein families. The new HEPN families include the RNase LS and LsoA catalytic domains, KEN domains (e.g. RNaseL and Ire1) and the RNase domains of RloC and PrrC. The majority of HEPN domains contain conserved motifs that constitute a metal-independent endoRNase active site. Some HEPN domains lacking this motif probably function as non-catalytic RNA-binding domains, such as in the case of the mannitol repressor MtlR. Our analysis shows that HEPN domains function as toxins that are shared by numerous systems implicated in intra-genomic, inter-genomic and intra-organismal conflicts across the three domains of cellular life. In prokaryotes HEPN domains are essential components of numerous toxin-antitoxin (TA) and abortive infection (Abi) systems and in addition are tightly associated with many restriction-modification (R-M) and CRISPR-Cas systems, and occasionally with other defense systems such as Pgl and Ter. We present evidence of multiple modes of action of HEPN domains in these systems, which include direct attack on viral RNAs (e.g. LsoA and RNase LS) in conjunction with other RNase domains (e.g. a novel RNase H fold domain, NamA), suicidal or dormancy-inducing attack on self RNAs (RM systems and possibly CRISPR-Cas systems), and suicidal attack coupled with direct interaction with phage components (Abi systems). These findings are compatible with the hypothesis on coupling of pathogen-targeting (immunity) and self-directed (programmed cell death and dormancy induction) responses in the evolution of robust antiviral strategies. We propose that altruistic cell suicide mediated by HEPN domains and other functionally similar RNases was essential for the evolution of kin and group selection and cell cooperation. HEPN domains were repeatedly acquired by eukaryotes and incorporated into several core functions such as endonucleolytic processing of the 5.8S-25S/28S rRNA precursor (Las1), a novel ER membrane-associated RNA degradation system (C6orf70), sensing of unprocessed transcripts at the nuclear periphery (Swt1). Multiple lines of evidence suggest that, similar to prokaryotes, HEPN proteins were recruited to antiviral, antitransposon, apoptotic systems or RNA-level response to unfolded proteins (Sacsin and KEN domains) in several groups of eukaryotes. CONCLUSIONS: Extensive sequence and structure comparisons reveal unexpectedly broad presence of the HEPN domain in an enormous variety of defense and stress response systems across the tree of life. In addition, HEPN domains have been recruited to perform essential functions, in particular in eukaryotic rRNA processing. These findings are expected to stimulate experiments that could shed light on diverse cellular processes across the three domains of life. REVIEWERS: This article was reviewed by Martijn Huynen, Igor Zhulin and Nick Grishin",2013 Jun 15,"['Anantharaman, Vivek', 'Makarova, Kira S', 'Burroughs, A Maxwell', 'Koonin, Eugene V', 'Aravind, L']",Biol Direct,,,True
c98f64c50d8a1c2d378db2e8da009c2dbc7936b1,PMC,Schistosomiasis control and the health system in P.R. China,http://dx.doi.org/10.1186/2049-9957-1-8,PMC3710143,23849320,CC BY,"Over the last sixty years advances have been made in the control of schistosomiasis in P.R. China. There are, however, difficult challenges still to be met. This paper looks at the extent to which the health system offers a positive environment for the control of the disease. It starts by tracing three phases in schistosomiasis control: disease elimination strategy through snail control (1950s-early 1980s); morbidity control strategy based on chemotherapy (mid 1980s to 2003); integrated control strategy (2004+). Each one of these phases took place in distinct policy-making environments. The paper partly draws on these phases to set out five issues of disease control and discusses them in the context of the health system and its recent trends. These cover the policy-making process, intersectoral action for health, equity and access to health services, funding for public goods and externalities, and strengthening resource management and planning. These issues form the basis of an agenda for integrating research and capacity strengthening in the Chinese health system with a view to creating a more positive enabling environment for schistosomiasis control. In so doing it is important to emphasize the role and integrity of the public sector against its commercialization, the underlying value of equity, a systems wide perspective, and the role of advocacy.",2012 Nov 1,"['Collins, Charles', 'Xu, Jing', 'Tang, Shenglan']",Infect Dis Poverty,,,True
cfb5101deb971a2922f94946edee44ebe7a7ac97,PMC,Schistosomiasis control and the health system in P.R. China,http://dx.doi.org/10.1186/2049-9957-1-8,PMC3710143,23849320,CC BY,"Over the last sixty years advances have been made in the control of schistosomiasis in P.R. China. There are, however, difficult challenges still to be met. This paper looks at the extent to which the health system offers a positive environment for the control of the disease. It starts by tracing three phases in schistosomiasis control: disease elimination strategy through snail control (1950s-early 1980s); morbidity control strategy based on chemotherapy (mid 1980s to 2003); integrated control strategy (2004+). Each one of these phases took place in distinct policy-making environments. The paper partly draws on these phases to set out five issues of disease control and discusses them in the context of the health system and its recent trends. These cover the policy-making process, intersectoral action for health, equity and access to health services, funding for public goods and externalities, and strengthening resource management and planning. These issues form the basis of an agenda for integrating research and capacity strengthening in the Chinese health system with a view to creating a more positive enabling environment for schistosomiasis control. In so doing it is important to emphasize the role and integrity of the public sector against its commercialization, the underlying value of equity, a systems wide perspective, and the role of advocacy.",2012 Nov 1,"['Collins, Charles', 'Xu, Jing', 'Tang, Shenglan']",Infect Dis Poverty,,,False
4209267ef4da6a8206733929e58967faebf8a5b7,PMC,Infectious disease emergence and global change: thinking systemically in a shrinking world,http://dx.doi.org/10.1186/2049-9957-1-5,PMC3710192,23849217,CC BY,"BACKGROUND: Concern intensifying that emerging infectious diseases and global environmental changes that could generate major future human pandemics. METHOD: A focused literature review was undertaken, partly informed by a forthcoming report on environment, agriculture and infectious diseases of poverty, facilitated by the Special Programme for Tropical Diseases. RESULTS: More than ten categories of infectious disease emergence exist, but none formally analyse past, current or future burden of disease. Other evidence suggests that the dominant public health concern focuses on two informal groupings. Most important is the perceived threat of newly recognised infections, especially viruses that arise or are newly discovered in developing countries that originate in species exotic to developed countries, such as non-human primates, bats and rodents. These pathogens may be transmitted by insects or bats, or via direct human contact with bushmeat. The second group is new strains of influenza arising from intensively farmed chickens or pigs, or emerging from Asian “wet markets” where several bird species have close contact. Both forms appear justified because of two great pandemics: HIV/AIDS (which appears to have originated from bushmeat hunting in Africa before emerging globally) and Spanish influenza, which killed up to 2.5% of the human population around the end of World War I. Insufficiently appreciated is the contribution of the milieu which appeared to facilitate the high disease burden in these pandemics. Additionally, excess anxiety over emerging infectious diseases diverts attention from issues of greater public health importance, especially: (i) existing (including neglected) infectious diseases and (ii) the changing milieu that is eroding the determinants of immunity and public health, caused by adverse global environmental changes, including climate change and other components of stressed life and civilisation-supporting systems. CONCLUSIONS: The focus on novel pathogens and minor forms of anti-microbial resistance in emerging disease literature is unjustified by their burden of disease, actual and potential, and diverts attention from far more important health problems and determinants. There is insufficient understanding of systemic factors that promote pandemics. Adverse global change could generate circumstances conducive to future pandemics with a high burden of disease, arising via anti-microbial and insecticidal resistance, under-nutrition, conflict, and public health breakdown.",2012 Oct 25,"Butler, Colin D",Infect Dis Poverty,,,True
6b659b911dd8957f6bda11eb20381946e3910564,PMC,Infectious disease emergence and global change: thinking systemically in a shrinking world,http://dx.doi.org/10.1186/2049-9957-1-5,PMC3710192,23849217,CC BY,"BACKGROUND: Concern intensifying that emerging infectious diseases and global environmental changes that could generate major future human pandemics. METHOD: A focused literature review was undertaken, partly informed by a forthcoming report on environment, agriculture and infectious diseases of poverty, facilitated by the Special Programme for Tropical Diseases. RESULTS: More than ten categories of infectious disease emergence exist, but none formally analyse past, current or future burden of disease. Other evidence suggests that the dominant public health concern focuses on two informal groupings. Most important is the perceived threat of newly recognised infections, especially viruses that arise or are newly discovered in developing countries that originate in species exotic to developed countries, such as non-human primates, bats and rodents. These pathogens may be transmitted by insects or bats, or via direct human contact with bushmeat. The second group is new strains of influenza arising from intensively farmed chickens or pigs, or emerging from Asian “wet markets” where several bird species have close contact. Both forms appear justified because of two great pandemics: HIV/AIDS (which appears to have originated from bushmeat hunting in Africa before emerging globally) and Spanish influenza, which killed up to 2.5% of the human population around the end of World War I. Insufficiently appreciated is the contribution of the milieu which appeared to facilitate the high disease burden in these pandemics. Additionally, excess anxiety over emerging infectious diseases diverts attention from issues of greater public health importance, especially: (i) existing (including neglected) infectious diseases and (ii) the changing milieu that is eroding the determinants of immunity and public health, caused by adverse global environmental changes, including climate change and other components of stressed life and civilisation-supporting systems. CONCLUSIONS: The focus on novel pathogens and minor forms of anti-microbial resistance in emerging disease literature is unjustified by their burden of disease, actual and potential, and diverts attention from far more important health problems and determinants. There is insufficient understanding of systemic factors that promote pandemics. Adverse global change could generate circumstances conducive to future pandemics with a high burden of disease, arising via anti-microbial and insecticidal resistance, under-nutrition, conflict, and public health breakdown.",2012 Oct 25,"Butler, Colin D",Infect Dis Poverty,,,False
5076cec908e9bc3ba685507e00ac19deab50b02e,PMC,Peptide-Based Vaccinology: Experimental and Computational Approaches to Target Hypervariable Viruses through the Fine Characterization of Protective Epitopes Recognized by Monoclonal Antibodies and the Identification of T-Cell-Activating Peptides,http://dx.doi.org/10.1155/2013/521231,PMC3710646,23878584,CC BY,"Defining immunogenic domains of viral proteins capable of eliciting a protective immune response is crucial in the development of novel epitope-based prophylactic strategies. This is particularly important for the selective targeting of conserved regions shared among hypervariable viruses. Studying postinfection and postimmunization sera, as well as cloning and characterization of monoclonal antibodies (mAbs), still represents the best approach to identify protective epitopes. In particular, a protective mAb directed against conserved regions can play a key role in immunogen design and in human therapy as well. Experimental approaches aiming to characterize protective mAb epitopes or to identify T-cell-activating peptides are often burdened by technical limitations and can require long time to be correctly addressed. Thus, in the last decade many epitope predictive algorithms have been developed. These algorithms are continually evolving, and their use to address the empirical research is widely increasing. Here, we review several strategies based on experimental techniques alone or addressed by in silico analysis that are frequently used to predict immunogens to be included in novel epitope-based vaccine approaches. We will list the main strategies aiming to design a new vaccine preparation conferring the protection of a neutralizing mAb combined with an effective cell-mediated response.",2013 Jun 26,"['Castelli, Matteo', 'Cappelletti, Francesca', 'Diotti, Roberta Antonia', 'Sautto, Giuseppe', 'Criscuolo, Elena', 'Dal Peraro, Matteo', 'Clementi, Nicola']",Clin Dev Immunol,,,True
3daf73ca2c2bb003b6f6201b1924660cc2fd75a2,PMC,Suppression of Coronavirus Replication by Cyclophilin Inhibitors,http://dx.doi.org/10.3390/v5051250,PMC3712306,23698397,CC BY,"Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS), feline infectious peritonitis (FIP), mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA), could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication.",2013 May 22,"['Tanaka, Yoshikazu', 'Sato, Yuka', 'Sasaki, Takashi']",Viruses,,,True
6129997a5fe45179b0acf89be52fe803bf5719dc,PMC,Microbial Translocation Contribute to Febrile Episodes in Adults with Chemotherapy-Induced Neutropenia,http://dx.doi.org/10.1371/journal.pone.0068056,PMC3712968,23874493,CC BY,"In this study we sought to determine the contribution of microbial translocation to febrile episodes with no attributable microbiological cause (Fever of Unknown Origin, FUO) in an adult febrile neutropaenic cohort. Endotoxin concentrations were measured with the chromogenic Limulus Amoebocyte Assay and used as a direct measure of bacterial products whilst soluble CD14 (sCD14), measured with ELISA was selected as an indicator of the early host response to endotoxins. Endotoxin concentrations in this cohort were generally elevated but did not differ with the presentation of fever. Further stratification of the febrile episodes based on the microbiological findings revealed significantly (p = 0.0077) elevated endotoxin concentrations in FUO episodes compared with episodes with documented bacterial and viral findings. sCD14 concentrations were however, elevated in febrile episodes (p = 0.0066) and no association was observed between sCD14 concentration and microbiological findings. However, FUO episodes and episodes with Gram-negative bacteraemia were associated with higher median sCD14 concentrations than episodes with Gram-positive bacteraemia (p = 0.030). In conclusion, our findings suggest that in the absence of microbiological findings, microbial translocation could contribute to febrile episodes in an adult neutropaenic cohort. We further observed an association between prophylactic antibiotic use and increased plasma endotoxin concentrations (p = 0.0212).",2013 Jul 16,"['Wong, Michelle', 'Barqasho, Babilonia', 'Öhrmalm, Lars', 'Tolfvenstam, Thomas', 'Nowak, Piotr']",PLoS One,,,True
374d22c2f8bc21e4e0525c7486d131db2cf607f4,PMC,Major Infection Events Over 5 Years: How Is Media Coverage Influencing Online Information Needs of Health Care Professionals and the Public?,http://dx.doi.org/10.2196/jmir.2146,PMC3713905,23856364,CC BY,"BACKGROUND: The last decade witnessed turbulent events in public health. Emerging infections, increase of antimicrobial resistance, deliberately released threats and ongoing battles with common illnesses were amplified by the spread of disease through increased international travel. The Internet has dramatically changed the availability of information about outbreaks; however, little research has been done in comparing the online behavior of public and professionals around the same events and the effect of media coverage of outbreaks on information needs. OBJECTIVE: To investigate professional and public online information needs around major infection outbreaks and correlate these with media coverage. Questions include (1) How do health care professionals’ online needs for public health and infection control information differ from those of the public?, (2) Does dramatic media coverage of outbreaks contribute to the information needs among the public?, and (3) How do incidents of diseases and major policy events relate to the information needs of professionals? METHODS: We used three longitudinal time-based datasets from mid-2006 until end of 2010: (1) a unique record of professional online behavior on UK infection portals: National electronic Library of Infection and National Resource of Infection Control (NeLI/NRIC), (2) equivalent public online information needs (Google Trends), and (3) relevant media coverage (LexisNexis). Analysis of NeLI/NRIC logs identified the highest interest around six major infectious diseases: Clostridium difficile (C difficile)/Methicillin-resistant Staphylococcus aureus (MRSA), tuberculosis, meningitis, norovirus, and influenza. After pre-processing, the datasets were analyzed and triangulated with each other. RESULTS: Public information needs were more static, following the actual disease occurrence less than those of professionals, whose needs increase with public health events (eg, MRSA/C difficile) and the release of major national policies or important documents. Media coverage of events resulted in major public interest (eg, the 2007/2008 UK outbreak of C difficile/MRSA). An exception was norovirus, showing a seasonal pattern for both public and professionals, which matched the periodic disease occurrence. Meningitis was a clear example of a disease with heightened media coverage tending to focus on individual and celebrity cases. Influenza was a major concern during the 2009 H1N1 outbreak creating massive public interest in line with the spring and autumn peaks in cases; although in autumn 2009, there was no corresponding increase in media coverage. Online resources play an increasing role in fulfilling professionals’ and public information needs. CONCLUSIONS: Significant factors related to a surge of professional interest around a disease were typically key publications and major policy changes. Public interests seem more static and correlate with media influence but to a lesser extent than expected. The only exception was norovirus, exhibiting online public and professional interest correlating with seasonal occurrences of the disease. Public health agencies with responsibility for risk communication of public health events, in particular during outbreaks and emergencies, need to collaborate with media in order to ensure the coverage is high quality and evidence-based, while professionals’ information needs remain mainly fulfilled by online open access to key resources.",2013 Jul 15,"['Kostkova, Patty', 'Fowler, David', 'Wiseman, Sue', 'Weinberg, Julius R']",J Med Internet Res,,,False
d479fdff7406604cebef7b82284ab7a275e17925,PMC,The Footprint of Genome Architecture in the Largest Genome Expansion in RNA Viruses,http://dx.doi.org/10.1371/journal.ppat.1003500,PMC3715407,23874204,CC BY,"The small size of RNA virus genomes (2-to-32 kb) has been attributed to high mutation rates during replication, which is thought to lack proof-reading. This paradigm is being revisited owing to the discovery of a 3′-to-5′ exoribonuclease (ExoN) in nidoviruses, a monophyletic group of positive-stranded RNA viruses with a conserved genome architecture. ExoN, a homolog of canonical DNA proof-reading enzymes, is exclusively encoded by nidoviruses with genomes larger than 20 kb. All other known non-segmented RNA viruses have smaller genomes. Here we use evolutionary analyses to show that the two- to three-fold expansion of the nidovirus genome was accompanied by a large number of replacements in conserved proteins at a scale comparable to that in the Tree of Life. To unravel common evolutionary patterns in such genetically diverse viruses, we established the relation between genomic regions in nidoviruses in a sequence alignment-free manner. We exploited the conservation of the genome architecture to partition each genome into five non-overlapping regions: 5′ untranslated region (UTR), open reading frame (ORF) 1a, ORF1b, 3′ORFs (encompassing the 3′-proximal ORFs), and 3′ UTR. Each region was analyzed for its contribution to genome size change under different models. The non-linear model statistically outperformed the linear one and captured >92% of data variation. Accordingly, nidovirus genomes were concluded to have reached different points on an expansion trajectory dominated by consecutive increases of ORF1b, ORF1a, and 3′ORFs. Our findings indicate a unidirectional hierarchical relation between these genome regions, which are distinguished by their expression mechanism. In contrast, these regions cooperate bi-directionally on a functional level in the virus life cycle, in which they predominantly control genome replication, genome expression, and virus dissemination, respectively. Collectively, our findings suggest that genome architecture and the associated region-specific division of labor leave a footprint on genome expansion and may limit RNA genome size.",2013 Jul 18,"['Lauber, Chris', 'Goeman, Jelle J.', 'Parquet, Maria del Carmen', 'Thi Nga, Phan', 'Snijder, Eric J.', 'Morita, Kouichi', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,True
a2e8d9291e399c6d8adc6d39318de197e86b3f4e,PMC,Antiviral Activity of Glycyrrhizin against Hepatitis C Virus In Vitro,http://dx.doi.org/10.1371/journal.pone.0068992,PMC3715454,23874843,CC BY,"Glycyrrhizin (GL) has been used in Japan to treat patients with chronic viral hepatitis, as an anti-inflammatory drug to reduce serum alanine aminotransferase levels. GL is also known to exhibit various biological activities, including anti-viral effects, but the anti-hepatitis C virus (HCV) effect of GL remains to be clarified. In this study, we demonstrated that GL treatment of HCV-infected Huh7 cells caused a reduction of infectious HCV production using cell culture-produced HCV (HCVcc). To determine the target step in the HCV lifecycle of GL, we used HCV pseudoparticles (HCVpp), replicon, and HCVcc systems. Significant suppressions of viral entry and replication steps were not observed. Interestingly, extracellular infectivity was decreased, and intracellular infectivity was increased. By immunofluorescence and electron microscopic analysis of GL treated cells, HCV core antigens and electron-dense particles had accumulated on endoplasmic reticulum attached to lipid droplet (LD), respectively, which is thought to act as platforms for HCV assembly. Furthermore, the amount of HCV core antigen in LD fraction increased. Taken together, these results suggest that GL inhibits release of infectious HCV particles. GL is known to have an inhibitory effect on phospholipase A2 (PLA2). We found that group 1B PLA2 (PLA2G1B) inhibitor also decreased HCV release, suggesting that suppression of virus release by GL treatment may be due to its inhibitory effect on PLA2G1B. Finally, we demonstrated that combination treatment with GL augmented IFN-induced reduction of virus in the HCVcc system. GL is identified as a novel anti-HCV agent that targets infectious virus particle release.",2013 Jul 18,"['Matsumoto, Yoshihiro', 'Matsuura, Tomokazu', 'Aoyagi, Haruyo', 'Matsuda, Mami', 'Hmwe, Su Su', 'Date, Tomoko', 'Watanabe, Noriyuki', 'Watashi, Koichi', 'Suzuki, Ryosuke', 'Ichinose, Shizuko', 'Wake, Kenjiro', 'Suzuki, Tetsuro', 'Miyamura, Tatsuo', 'Wakita, Takaji', 'Aizaki, Hideki']",PLoS One,,,True
a7e3179a2dbf9f386ac702c0a6fc780889773829,PMC,Lithium chloride promotes host resistance against Pseudomonas aeruginosa keratitis,,PMC3716469,23878501,CC BY,"PURPOSE: To explore the role of lithium chloride (LiCl) in Pseudomonas aeruginosa (PA) keratitis. METHODS: B6 mice were subconjunctivally injected with LiCl in contrast to appropriate control sodium chloride (NaCl), and then routinely infected with PA. Clinical score, slit-lamp photography, hematoxylin and eosin (H&E) staining, and bacterial plate counts were used to determine the role of LiCl in PA keratitis. Messenger ribonucleic acid and protein levels of inflammatory cytokines in PA-challenged mouse corneas and in vitro cultured macrophages and neutrophils were measured with real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Apoptosis of the infiltrating inflammatory cells in the PA-infected murine corneas was assessed using terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling staining and propidium iodide staining associated with flow cytometry. In cultured murine macrophages and neutrophils, cell apoptosis was determined with annexin V/propidium iodide double staining associated with flow cytometry and western blot analysis for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase. RESULTS: Treatment with LiCl reduced the severity of corneal disease by reducing corneal inflammatory response and bacterial burden. Moreover, LiCl increased anti-inflammatory cytokine interleukin-10 levels, decreased proinflammatory cytokine tumor necrosis factor-α levels, and enhanced apoptosis of infiltrating macrophages and neutrophils in the PA-infected mouse corneas. In vitro studies further confirmed that LiCl elevated anti-inflammatory cytokine expression but reduced proinflammatory cytokine production, as well as promoted cell apoptosis in murine macrophages and neutrophils. CONCLUSIONS: This study demonstrates a protective role of LiCl in PA keratitis. LiCl promotes host resistance against PA infection by suppressing inflammatory responses, enhancing inflammatory cell apoptosis, and promoting bacterial clearance.",2013 Jul 19,"['Chen, Kang', 'Wu, Yongjian', 'Zhu, Min', 'Deng, Qiuchan', 'Nie, Xinxin', 'Li, Meiyu', 'Wu, Minhao', 'Huang, Xi']",Mol Vis,,,True
e4387a9c18bca710c7fdc986a6b2f8df671e29b8,PMC,"Isolation and genetic characterization of human coronavirus NL63 in primary human renal proximal tubular epithelial cells obtained from a commercial supplier, and confirmation of its replication in two different types of human primary kidney cells",http://dx.doi.org/10.1186/1743-422X-10-213,PMC3716658,23805916,CC BY,"BACKGROUND: Cryopreserved primary human renal proximal tubule epithelial cells (RPTEC) were obtained from a commercial supplier for studies of Simian virus 40 (SV40). Within twelve hrs after cell cultures were initiated, cytoplasmic vacuoles appeared in many of the RPTEC. The RPTEC henceforth deteriorated rapidly. Since SV40 induces the formation of cytoplasmic vacuoles, this batch of RPTEC was rejected for the SV40 study. Nevertheless, we sought the likely cause(s) of the deterioration of the RPTEC as part of our technology development efforts. METHODS: Adventitious viruses in the RPTEC were isolated and/or detected and identified by isolation in various indicator cell lines, observation of cytopathology, an immunoflurorescence assay, electron microscopy, PCR, and sequencing. RESULTS: Cytomegalovirus (CMV) was detected in some RPTEC by cytology, an immunofluorescence assay, and PCR. Human Herpesvirus 6B was detected by PCR of DNA extracted from the RPTEC, but was not isolated. Human coronavirus NL63 was isolated and identified by RT-PCR and sequencing, and its replication in a fresh batch of RPTEC and another type of primary human kidney cells was confirmed. CONCLUSIONS: At least 3 different adventitious viruses were present in the batch of contaminated RPTEC. Whereas we are unable to determine whether the original RPTEC were pre-infected prior to their separation from other kidney cells, or had gotten contaminated with HCoV-NL63 from an ill laboratory worker during their preparation for commercial sale, our findings are a reminder that human-derived biologicals should always be considered as potential sources of infectious agents. Importantly, HCoV-NL63 replicates to high titers in some primary human kidney cells.",2013 Jun 27,"['Lednicky, John A', 'Waltzek, Thomas B', 'McGeehan, Elizabeth', 'Loeb, Julia C', 'Hamilton, Sara B', 'Luetke, Maya C']",Virol J,,,True
40540b92cbf5d985e0648733de6f4a9062e1bbcf,PMC,Genetic characterization of EV71 isolates from 2004 to 2010 reveals predominance and persistent circulation of the newly proposed genotype D and recent emergence of a distinct lineage of subgenotype C2 in Hong Kong,http://dx.doi.org/10.1186/1743-422X-10-222,PMC3716818,23822185,CC BY,"BACKGROUND: Enterovirus 71 (EV71) is a common etiological agent of hand, foot and mouth disease (HFMD) in children. EV71 epidemics have been reported in Hong Kong in recent years, and yet the genetic information of EV71 strains circulating in our locality is limited. The objective of this study was to investigate the genetic evolution of these EV71 isolates in Hong Kong over a 7-year period. METHODS: Twenty-two EV71 isolates from Hong Kong during 2004–2010 were included for phylogenetic analysis using partial VP2-VP3, 2C and 3D regions. Eight EV71 strains were selected for complete genome sequencing and recombination analysis. RESULTS: Among the 22 EV71 isolates, 20 belonged to subgenotype C4 and 2 belonged to subgenotype C2 based on the phylogenetic analysis of partial VP2-VP3, 2C and 3D gene regions. Phylogenetic, similarity plot and bootscan analyses using complete genome sequences of seven EV71 isolates of subgenotype C4 supported that the “double-recombinant” strains of subgenotype C4 persistently circulating in Hong Kong should belong to a newly proposed genotype D. Further analysis revealed two clusters, subgenotypes C4b and C4a (proposed genotypes D1a and D1b respectively), with “genotype D1b” strains being predominant in recent years in Hong Kong. A distinct lineage of EV71 subgenotype C2 has emerged in Hong Kong in 2008. The evolutionary rate of EV71 was 3.1 × 10(-3) nucleotide substitutions per site per year similar to that of other enterovirus, such as EV68, but was relatively lower than those of echovirus 30 and poliovirus. Molecular clock analysis using VP1 gene dated the time to the most recent common ancestor of all EV71 genotypes to 1900s, while the EV71 “double-recombinant” strains of “genotype D” were detected as early as 1998. CONCLUSIONS: This study provides the molecular basis for proposing a new “genotype D” of EV71 and assigning a discrete lineage of subgenotype C2. EV71 strains of “genotype D” have been circulating in Hong Kong for over 7 years, with “genotype D1b” being predominant.",2013 Jul 4,"['Yip, Cyril CY', 'Lau, Susanna KP', 'Lo, Janice YC', 'Chan, Kwok-Hung', 'Woo, Patrick CY', 'Yuen, Kwok-Yung']",Virol J,,,True
59cd9fecfcd1ef7eb2bbe427809ef0fd01e894b5,PMC,Maintaining the structural integrity of the bamboo mosaic virus 3′ untranslated region is necessary for retaining the catalytic constant for minus-strand RNA synthesis,http://dx.doi.org/10.1186/1743-422X-10-208,PMC3720222,23800142,CC BY,"BACKGROUND: Bamboo mosaic virus (BaMV) and the Potato virus X (PVX) are members of the genus Potexvirus and have a single-stranded positive-sense RNA genome. The 3′-untranslated region (UTR) of the BaMV RNA genome was mapped structurally into ABC (a cloverleaf-like), D (a stem-loop), and E (pseudoknot) domains. The BaMV replicase complex that was isolated from the infected plants was able to recognize the 3′ UTR of PVX RNA to initiate minus-strand RNA synthesis in vitro. RESULTS: To investigate whether the 3′ UTR of PVX RNA is also compatible with BaMV replicase in vivo, we constructed chimera mutants using a BaMV backbone containing the PVX 3′ UTR, which was inserted in or used to replace the various domains in the 3′ UTR of BaMV. None of the mutants, except for the mutant with the PVX 3′ UTR inserted upstream of the BaMV 3′ UTR, exhibited a detectable accumulation of viral RNA in Nicotiana benthamiana plants. The in vitro BaMV RdRp replication assay demonstrated that the RNA products were generated by the short RNA transcripts, which were derived from the chimera mutants to various extents. Furthermore, the V(max)/K(M) of the BaMV 3′ UTR (rABCDE) was approximately three fold higher than rABCP, rP, and rDE in minus-strand RNA synthesis. These mutants failed to accumulate viral products in protoplasts and plants, but were adequately replicated in vitro. CONCLUSIONS: Among the various studied BaMV/PVX chimera mutants, the BaMV-S/PABCDE that contained non-interrupted BaMV 3′ UTR was the only mutant that exhibited a wild-type level of viral product accumulation in protoplasts and plants. These results indicate that the continuity of the domains in the 3′ UTR of BaMV RNA was not interrupted and the domains were not replaced with the 3′ UTR of PVX RNA in vivo.",2013 Jun 24,"['Chen, I-Hsuan', 'Chu, Chiu-Heiu', 'Lin, Jen-Wen', 'Hsu, Yau-Heiu', 'Tsai, Ching-Hsiu']",Virol J,,,True
520074edb06a53db798395f49940fb5d24417b62,PMC,Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 4 Induces Apoptosis Dependent on Its 3C-Like Serine Protease Activity,http://dx.doi.org/10.1371/journal.pone.0069387,PMC3720278,23936003,CC BY,"Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease in pigs caused by PRRS virus (PRRSV). Although PRRSV infection-induced cell apoptosis has been established, the related viral protein is still unknown. Here, we reported that PRRSV nonstructural protein 4 (nsp4) was a critical apoptosis inducer. Nsp4 could activate caspase-3, -8, and -9. Using truncated constructs without different domains in nsp4, we demonstrated that the full-length of nsp4 structure was required for its apoptosis-inducing activity. Furthermore, using site-directed mutagenesis to inactivate the 3C-like serine protease activity of nsp4, we showed that nsp4-induced apoptosis was dependent on its serine protease activity. The ability of nsp4 to induce apoptosis was significantly impaired by His39, Asp64, and Ser118 mutations, suggesting that His39, Asp64, and Ser118 were essential for nsp4 to trigger apoptosis. In conclusion, our present work showed that PRRSV nsp4 could induce apoptosis in host cells and might be partially responsible for the apoptosis induced by PRRSV infection. PRRSV 3C-like protease-mediated apoptosis represents the first report in the genus Arterivirus, family Arteriviridae.",2013 Jul 23,"['Ma, Zhitao', 'Wang, Yalan', 'Zhao, Haiyan', 'Xu, Ao-Tian', 'Wang, Yongqiang', 'Tang, Jun', 'Feng, Wen-hai']",PLoS One,,,True
e9c899d06f0e31a0d2c58cd4d82edb0086f9ed04,PMC,An outbreak of feline infectious peritonitis in a Taiwanese shelter: epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus,http://dx.doi.org/10.1186/1297-9716-44-57,PMC3720556,23865689,CC BY,"Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus (FCoV) infection. FCoV can be divided into serotypes I and II. The virus that causes FIP (FIPV) is believed to occur sporadically and spread infrequently from cat to cat. Recently, an FIP outbreak from an animal shelter was confirmed in Taiwan. FCoV from all the cats in this shelter were analyzed to determine the epidemiology of this outbreak. Thirteen of 46 (28.2%) cats with typical signs of FIP were identified. Among them, seven cats were confirmed by necropsy and/or histopathological examinations. Despite the fact that more than one FCoV was identified in this multi-cat environment, the eight FIP cats were invariably found to be infected with a type II FCoV. Sequence analysis revealed that the type II FIPV detected from fecal samples, body effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene. Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene. Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death. Taken together, our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment.",2013 Jul 17,"['Wang, Ying-Ting', 'Su, Bi-Ling', 'Hsieh, Li-En', 'Chueh, Ling-Ling']",Vet Res,,,True
10fbf7274b0bdfe7153269489851fc3d8f121bcd,PMC,Characterization of Rotavirus RNAs That Activate Innate Immune Signaling through the RIG-I-Like Receptors,http://dx.doi.org/10.1371/journal.pone.0069825,PMC3720929,23894547,CC BY,"In mammalian cells, the first line of defense against viral pathogens is the innate immune response, which is characterized by induction of type I interferons (IFN) and other pro-inflammatory cytokines that establish an antiviral milieu both in infected cells and in neighboring uninfected cells. Rotavirus, a double-stranded RNA virus of the Reoviridae family, is the primary etiological agent of severe diarrhea in young children worldwide. Previous studies demonstrated that rotavirus replication induces a MAVS-dependent type I IFN response that involves both RIG-I and MDA5, two cytoplasmic viral RNA sensors. This study reports the isolation and characterization of rotavirus RNAs that activate IFN signaling. Using an in vitro approach with purified rotavirus double-layer particles, nascent single-stranded RNA (ssRNA) transcripts (termed in vitro ssRNA) were found to be potent IFN inducers. In addition, large RNAs isolated from rotavirus-infected cells six hours post-infection (termed in vivo 6 hr large RNAs), also activated IFN signaling, whereas a comparable large RNA fraction isolated from cells infected for only one hour lacked this stimulatory activity. Experiments using knockout murine embryonic fibroblasts showed that RIG-I is required for and MDA5 partly contributes to innate immune signaling by both in vitro ssRNA and in vivo 6 hr large RNAs. Enzymatic studies demonstrated that in vitro ssRNA and in vivo 6 hr large RNA samples contain uncapped RNAs with exposed 5’ phosphate groups. RNAs lacking 2’-O-methylated 5’ cap structures were also detected in the in vivo 6 hr large RNA sample. Taken together, our data provide strong evidence that the rotavirus VP3 enzyme, which encodes both guanylyltransferase and methyltransferase activities, is not completely efficient at either 5’ capping or 2’-O-methylation of the 5’ cap structures of viral transcripts, and in this way produces RNA patterns that activate innate immune signaling through the RIG-I-like receptors.",2013 Jul 23,"['Uzri, Dina', 'Greenberg, Harry B.']",PLoS One,,,True
b59b58c13370a390a58c6cd79e61f97bf9bee37d,PMC,Development of an Aerosol Model of Cryptococcus Reveals Humidity as an Important Factor Affecting the Viability of Cryptococcus during Aerosolization,http://dx.doi.org/10.1371/journal.pone.0069804,PMC3720958,23894542,CC BY,"Cryptococcus is an emerging global health threat that is annually responsible for over 1,000,000 infections and one third of all AIDS patient deaths. There is an ongoing outbreak of cryptococcosis in the western United States and Canada. Cryptococcosis is a disease resulting from the inhalation of the infectious propagules from the environment. The current and most frequently used animal infection models initiate infection via liquid suspension through intranasal instillation or intravenous injection. These models do not replicate the typically dry nature of aerosol exposure and may hinder our ability to decipher the initial events that lead to clearance or the establishment of infection. We have established a standardized aerosol model of murine infection for the human fungal pathogen Cryptococcus. Aerosolized cells were generated utilizing a Collison nebulizer in a whole-body Madison Chamber at different humidity conditions. The aerosols inside the chamber were sampled using a BioSampler to determine viable aerosol concentration and spray factor (ratio of viable aerosol concentration to total inoculum concentration). We have effectively delivered yeast and yeast-spore mixtures to the lungs of mice and observed the establishment of disease. We observed that growth conditions prior to exposure and humidity within the Madison Chamber during exposure can alter Cryptococcus survival and dose retained in mice.",2013 Jul 23,"['Springer, Deborah J.', 'Saini, Divey', 'Byrnes, Edmond J.', 'Heitman, Joseph', 'Frothingham, Richard']",PLoS One,,,True
61573a5ebe4f84a5b5738bc12a3c18d2bf69651c,PMC,The Role of FGL2 in the Pathogenesis and Treatment of Hepatitis C Virus Infection,http://dx.doi.org/10.5041/RMMJ.10004,PMC3721661,23908776,CC BY,"Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease worldwide and remains the most common indication for liver transplantation. The current standard of care leads to a sustained viral response of roughly 50% of treated patients at best. Furthermore, anti-viral therapy is expensive, prolonged, and associated with serious side-effects. Evidence suggests that a poor response to treatment may be the result of a suppressed anti-viral immunity due to the presence of increased numbers and activity of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg cells). We and others have recently identified fibrinogen-like protein 2 (FGL2) as a putative effector of Treg cells, which accounts for their suppressive function through binding to Fc gamma receptors (FcγR). In an experimental model of fulminant viral hepatitis, our laboratory showed that increased plasma levels of FGL2 pre- and post-viral infection were predictive of susceptibility and severity of disease. Moreover, treatment with antibody to FGL2 fully protected susceptible animals from the lethality of the virus, and adoptive transfer of wild-type Treg cells into resistant fgl2-deficient animals accelerated their mortality post-infection. In patients with HCV infection, plasma levels of FGL2 and expression of FGL2 in the liver correlated with the course and severity of the disease. Collectively, these studies suggest that FGL2 may be used as a biomarker to predict disease progression in HCV patients and be a logical target for the development of novel therapeutic approaches for the treatment of patients with HCV infection.",2010 Jul 2,"['Shalev, Itay', 'Selzner, Nazia', 'Helmy, Ahmed', 'Foerster, Katharina', 'Adeyi, Oyedele A.', 'Grant, David R.', 'Levy, Gary']",Rambam Maimonides Med J,,,True
4e6709b68cb7312fda8a1c5a2b2505d21a38a1e9,PMC,Human Coronavirus HKU1 Infection of Primary Human Type II Alveolar Epithelial Cells: Cytopathic Effects and Innate Immune Response,http://dx.doi.org/10.1371/journal.pone.0070129,PMC3722178,23894604,CC BY,"Because they are the natural target for respiratory pathogens, primary human respiratory epithelial cells provide the ideal in vitro system for isolation and study of human respiratory viruses, which display a high degree of cell, tissue, and host specificity. Human coronavirus HKU1, first discovered in 2005, has a worldwide prevalence and is associated with both upper and lower respiratory tract disease in both children and adults. Research on HCoV-HKU1 has been difficult because of its inability to be cultured on continuous cell lines and only recently it was isolated from clinical specimens using primary human, ciliated airway epithelial cells. Here we demonstrate that HCoV-HKU1 can infect and be serially propagated in primary human alveolar type II cells at the air-liquid interface. We were not able to infect alveolar type I-like cells or alveolar macrophages. Type II alveolar cells infected with HCoV-HKU1 demonstrated formation of large syncytium. At 72 hours post inoculation, HCoV-HKU1 infection of type II cells induced increased levels of mRNAs encoding IL29,CXCL10, CCL5, and IL-6 with no significant increases in the levels of IFNβ. These studies demonstrate that type II cells are a target cell for HCoV-HKU1 infection in the lower respiratory tract, that type II alveolar cells are immune-competent in response to infection exhibiting a type III interferon and proinflammatory chemokine response, and that cell to cell spread may be a major factor for spread of infection. Furthermore, these studies demonstrate that human alveolar cells can be used to isolate and study novel human respiratory viruses that cause lower respiratory tract disease.",2013 Jul 24,"['Dominguez, Samuel R.', 'Travanty, Emily A.', 'Qian, Zhaohui', 'Mason, Robert J.']",PLoS One,,,True
b6761b66c1494299587710188e9a371713d88450,PMC,Experimental Cross-Species Infection of Common Marmosets by Titi Monkey Adenovirus,http://dx.doi.org/10.1371/journal.pone.0068558,PMC3722195,23894316,CC BY,"Adenoviruses are DNA viruses that infect a number of vertebrate hosts and are associated with both sporadic and epidemic disease in humans. We previously identified a novel adenovirus, titi monkey adenovirus (TMAdV), as the cause of a fulminant pneumonia outbreak in a colony of titi monkeys (Callicebus cupreus) at a national primate center in 2009. Serological evidence of infection by TMAdV was also found in a human researcher at the facility and household family member, raising concerns for potential cross-species transmission of the virus. Here we present experimental evidence of cross-species TMAdV infection in common marmosets (Callithrix jacchus). Nasal inoculation of a cell cultured-adapted TMAdV strain into three marmosets produced an acute, mild respiratory illness characterized by low-grade fever, reduced activity, anorexia, and sneezing. An increase in virus-specific neutralization antibody titers accompanied the development of clinical signs. Although serially collected nasal swabs were positive for TMAdV for at least 8 days, all 3 infected marmosets spontaneously recovered by day 12 post-inoculation, and persistence of the virus in tissues could not be established. Thus, the pathogenesis of experimental inoculation of TMAdV in common marmosets resembled the mild, self-limiting respiratory infection typically seen in immunocompetent human hosts rather than the rapidly progressive, fatal pneumonia observed in 19 of 23 titi monkeys during the prior 2009 outbreak. These findings further establish the potential for adenovirus cross-species transmission and provide the basis for development of a monkey model useful for assessing the zoonotic potential of adenoviruses.",2013 Jul 24,"['Yu, Guixia', 'Yagi, Shigeo', 'Carrion, Ricardo', 'Chen, Eunice C.', 'Liu, Maria', 'Brasky, Kathleen M.', 'Lanford, Robert E.', 'Kelly, Kristi R.', 'Bales, Karen L.', 'Schnurr, David P.', 'Canfield, Don R.', 'Patterson, Jean L.', 'Chiu, Charles Y.']",PLoS One,,,True
ec5801ab0b12fb9b83869ca6b56261cc0ee5a458,PMC,Experimental Cross-Species Infection of Common Marmosets by Titi Monkey Adenovirus,http://dx.doi.org/10.1371/journal.pone.0068558,PMC3722195,23894316,CC BY,"Adenoviruses are DNA viruses that infect a number of vertebrate hosts and are associated with both sporadic and epidemic disease in humans. We previously identified a novel adenovirus, titi monkey adenovirus (TMAdV), as the cause of a fulminant pneumonia outbreak in a colony of titi monkeys (Callicebus cupreus) at a national primate center in 2009. Serological evidence of infection by TMAdV was also found in a human researcher at the facility and household family member, raising concerns for potential cross-species transmission of the virus. Here we present experimental evidence of cross-species TMAdV infection in common marmosets (Callithrix jacchus). Nasal inoculation of a cell cultured-adapted TMAdV strain into three marmosets produced an acute, mild respiratory illness characterized by low-grade fever, reduced activity, anorexia, and sneezing. An increase in virus-specific neutralization antibody titers accompanied the development of clinical signs. Although serially collected nasal swabs were positive for TMAdV for at least 8 days, all 3 infected marmosets spontaneously recovered by day 12 post-inoculation, and persistence of the virus in tissues could not be established. Thus, the pathogenesis of experimental inoculation of TMAdV in common marmosets resembled the mild, self-limiting respiratory infection typically seen in immunocompetent human hosts rather than the rapidly progressive, fatal pneumonia observed in 19 of 23 titi monkeys during the prior 2009 outbreak. These findings further establish the potential for adenovirus cross-species transmission and provide the basis for development of a monkey model useful for assessing the zoonotic potential of adenoviruses.",2013 Jul 24,"['Yu, Guixia', 'Yagi, Shigeo', 'Carrion, Ricardo', 'Chen, Eunice C.', 'Liu, Maria', 'Brasky, Kathleen M.', 'Lanford, Robert E.', 'Kelly, Kristi R.', 'Bales, Karen L.', 'Schnurr, David P.', 'Canfield, Don R.', 'Patterson, Jean L.', 'Chiu, Charles Y.']",PLoS One,,,False
6ea0e6352fac7379789d023be2d4b7924a98fd8b,PMC,Experimental Cross-Species Infection of Common Marmosets by Titi Monkey Adenovirus,http://dx.doi.org/10.1371/journal.pone.0068558,PMC3722195,23894316,CC BY,"Adenoviruses are DNA viruses that infect a number of vertebrate hosts and are associated with both sporadic and epidemic disease in humans. We previously identified a novel adenovirus, titi monkey adenovirus (TMAdV), as the cause of a fulminant pneumonia outbreak in a colony of titi monkeys (Callicebus cupreus) at a national primate center in 2009. Serological evidence of infection by TMAdV was also found in a human researcher at the facility and household family member, raising concerns for potential cross-species transmission of the virus. Here we present experimental evidence of cross-species TMAdV infection in common marmosets (Callithrix jacchus). Nasal inoculation of a cell cultured-adapted TMAdV strain into three marmosets produced an acute, mild respiratory illness characterized by low-grade fever, reduced activity, anorexia, and sneezing. An increase in virus-specific neutralization antibody titers accompanied the development of clinical signs. Although serially collected nasal swabs were positive for TMAdV for at least 8 days, all 3 infected marmosets spontaneously recovered by day 12 post-inoculation, and persistence of the virus in tissues could not be established. Thus, the pathogenesis of experimental inoculation of TMAdV in common marmosets resembled the mild, self-limiting respiratory infection typically seen in immunocompetent human hosts rather than the rapidly progressive, fatal pneumonia observed in 19 of 23 titi monkeys during the prior 2009 outbreak. These findings further establish the potential for adenovirus cross-species transmission and provide the basis for development of a monkey model useful for assessing the zoonotic potential of adenoviruses.",2013 Jul 24,"['Yu, Guixia', 'Yagi, Shigeo', 'Carrion, Ricardo', 'Chen, Eunice C.', 'Liu, Maria', 'Brasky, Kathleen M.', 'Lanford, Robert E.', 'Kelly, Kristi R.', 'Bales, Karen L.', 'Schnurr, David P.', 'Canfield, Don R.', 'Patterson, Jean L.', 'Chiu, Charles Y.']",PLoS One,,,False
5b070d94a23c10061ed3f494fad703429fe8c1a0,PMC,Experimental Cross-Species Infection of Common Marmosets by Titi Monkey Adenovirus,http://dx.doi.org/10.1371/journal.pone.0068558,PMC3722195,23894316,CC BY,"Adenoviruses are DNA viruses that infect a number of vertebrate hosts and are associated with both sporadic and epidemic disease in humans. We previously identified a novel adenovirus, titi monkey adenovirus (TMAdV), as the cause of a fulminant pneumonia outbreak in a colony of titi monkeys (Callicebus cupreus) at a national primate center in 2009. Serological evidence of infection by TMAdV was also found in a human researcher at the facility and household family member, raising concerns for potential cross-species transmission of the virus. Here we present experimental evidence of cross-species TMAdV infection in common marmosets (Callithrix jacchus). Nasal inoculation of a cell cultured-adapted TMAdV strain into three marmosets produced an acute, mild respiratory illness characterized by low-grade fever, reduced activity, anorexia, and sneezing. An increase in virus-specific neutralization antibody titers accompanied the development of clinical signs. Although serially collected nasal swabs were positive for TMAdV for at least 8 days, all 3 infected marmosets spontaneously recovered by day 12 post-inoculation, and persistence of the virus in tissues could not be established. Thus, the pathogenesis of experimental inoculation of TMAdV in common marmosets resembled the mild, self-limiting respiratory infection typically seen in immunocompetent human hosts rather than the rapidly progressive, fatal pneumonia observed in 19 of 23 titi monkeys during the prior 2009 outbreak. These findings further establish the potential for adenovirus cross-species transmission and provide the basis for development of a monkey model useful for assessing the zoonotic potential of adenoviruses.",2013 Jul 24,"['Yu, Guixia', 'Yagi, Shigeo', 'Carrion, Ricardo', 'Chen, Eunice C.', 'Liu, Maria', 'Brasky, Kathleen M.', 'Lanford, Robert E.', 'Kelly, Kristi R.', 'Bales, Karen L.', 'Schnurr, David P.', 'Canfield, Don R.', 'Patterson, Jean L.', 'Chiu, Charles Y.']",PLoS One,,,False
38709b5c18e24c3287a6b1b97ddbe8899cdab432,PMC,Use of Hangeul Twitter to Track and Predict Human Influenza Infection,http://dx.doi.org/10.1371/journal.pone.0069305,PMC3722273,23894447,CC BY,"Influenza epidemics arise through the accumulation of viral genetic changes. The emergence of new virus strains coincides with a higher level of influenza-like illness (ILI), which is seen as a peak of a normal season. Monitoring the spread of an epidemic influenza in populations is a difficult and important task. Twitter is a free social networking service whose messages can improve the accuracy of forecasting models by providing early warnings of influenza outbreaks. In this study, we have examined the use of information embedded in the Hangeul Twitter stream to detect rapidly evolving public awareness or concern with respect to influenza transmission and developed regression models that can track levels of actual disease activity and predict influenza epidemics in the real world. Our prediction model using a delay mode provides not only a real-time assessment of the current influenza epidemic activity but also a significant improvement in prediction performance at the initial phase of ILI peak when prediction is of most importance.",2013 Jul 24,"['Kim, Eui-Ki', 'Seok, Jong Hyeon', 'Oh, Jang Seok', 'Lee, Hyong Woo', 'Kim, Kyung Hyun']",PLoS One,,,True
d5fbbe644c1b4979ea69e57eac5061ce2e3a71ca,PMC,Use of Hangeul Twitter to Track and Predict Human Influenza Infection,http://dx.doi.org/10.1371/journal.pone.0069305,PMC3722273,23894447,CC BY,"Influenza epidemics arise through the accumulation of viral genetic changes. The emergence of new virus strains coincides with a higher level of influenza-like illness (ILI), which is seen as a peak of a normal season. Monitoring the spread of an epidemic influenza in populations is a difficult and important task. Twitter is a free social networking service whose messages can improve the accuracy of forecasting models by providing early warnings of influenza outbreaks. In this study, we have examined the use of information embedded in the Hangeul Twitter stream to detect rapidly evolving public awareness or concern with respect to influenza transmission and developed regression models that can track levels of actual disease activity and predict influenza epidemics in the real world. Our prediction model using a delay mode provides not only a real-time assessment of the current influenza epidemic activity but also a significant improvement in prediction performance at the initial phase of ILI peak when prediction is of most importance.",2013 Jul 24,"['Kim, Eui-Ki', 'Seok, Jong Hyeon', 'Oh, Jang Seok', 'Lee, Hyong Woo', 'Kim, Kyung Hyun']",PLoS One,,,False
73104fbdc161f1cea305271bdd1a2f11bf49bdc2,PMC,Use of Hangeul Twitter to Track and Predict Human Influenza Infection,http://dx.doi.org/10.1371/journal.pone.0069305,PMC3722273,23894447,CC BY,"Influenza epidemics arise through the accumulation of viral genetic changes. The emergence of new virus strains coincides with a higher level of influenza-like illness (ILI), which is seen as a peak of a normal season. Monitoring the spread of an epidemic influenza in populations is a difficult and important task. Twitter is a free social networking service whose messages can improve the accuracy of forecasting models by providing early warnings of influenza outbreaks. In this study, we have examined the use of information embedded in the Hangeul Twitter stream to detect rapidly evolving public awareness or concern with respect to influenza transmission and developed regression models that can track levels of actual disease activity and predict influenza epidemics in the real world. Our prediction model using a delay mode provides not only a real-time assessment of the current influenza epidemic activity but also a significant improvement in prediction performance at the initial phase of ILI peak when prediction is of most importance.",2013 Jul 24,"['Kim, Eui-Ki', 'Seok, Jong Hyeon', 'Oh, Jang Seok', 'Lee, Hyong Woo', 'Kim, Kyung Hyun']",PLoS One,,,False
ccaafc13b2c1551dce74e1a7fe3e43cea5228732,PMC,A Network Integration Approach to Predict Conserved Regulators Related to Pathogenicity of Influenza and SARS-CoV Respiratory Viruses,http://dx.doi.org/10.1371/journal.pone.0069374,PMC3723910,23935999,CC0,"Respiratory infections stemming from influenza viruses and the Severe Acute Respiratory Syndrome corona virus (SARS-CoV) represent a serious public health threat as emerging pandemics. Despite efforts to identify the critical interactions of these viruses with host machinery, the key regulatory events that lead to disease pathology remain poorly targeted with therapeutics. Here we implement an integrated network interrogation approach, in which proteome and transcriptome datasets from infection of both viruses in human lung epithelial cells are utilized to predict regulatory genes involved in the host response. We take advantage of a novel “crowd-based” approach to identify and combine ranking metrics that isolate genes/proteins likely related to the pathogenicity of SARS-CoV and influenza virus. Subsequently, a multivariate regression model is used to compare predicted lung epithelial regulatory influences with data derived from other respiratory virus infection models. We predicted a small set of regulatory factors with conserved behavior for consideration as important components of viral pathogenesis that might also serve as therapeutic targets for intervention. Our results demonstrate the utility of integrating diverse ‘omic datasets to predict and prioritize regulatory features conserved across multiple pathogen infection models.",2013 Jul 25,"['Mitchell, Hugh D.', 'Eisfeld, Amie J.', 'Sims, Amy C.', 'McDermott, Jason E.', 'Matzke, Melissa M.', 'Webb-Robertson, Bobbi-Jo M.', 'Tilton, Susan C.', 'Tchitchek, Nicolas', 'Josset, Laurence', 'Li, Chengjun', 'Ellis, Amy L.', 'Chang, Jean H.', 'Heegel, Robert A.', 'Luna, Maria L.', 'Schepmoes, Athena A.', 'Shukla, Anil K.', 'Metz, Thomas O.', 'Neumann, Gabriele', 'Benecke, Arndt G.', 'Smith, Richard D.', 'Baric, Ralph S.', 'Kawaoka, Yoshihiro', 'Katze, Michael G.', 'Waters, Katrina M.']",PLoS One,,,True
fb8dfa6988a6f08b4b64a0d5c7843c854a8328d0,PMC,Computational modeling of the p7 monomer from HCV and its interaction with small molecule drugs,http://dx.doi.org/10.1186/2193-1801-2-324,PMC3724979,23961398,CC BY,"Hepatitis C virus p7 protein is a 63 amino acid polytopic protein with two transmembrane domains (TMDs) and one of the prime targets for anti HCV drug development. A bio-inspired modeling pathway is used to generate plausible computational models of the two TMDs forming the monomeric protein model. A flexible region between Leu-13 and Gly-15 is identified for TMD1(1-32) and a region around Gly-46 to Trp-48 for TMD2(36-58). Mutations of the tyrosine residues in TMD2(36-58) into phenylalanine and serine are simulated to identify their role in shaping TMD2. Lowest energy structures of the two TMDs connected with the loop residues are used for a posing study in which small molecule drugs BIT225, amantadine, rimantadine and NN-DNJ, are identified to bind to the loop region. BIT225 is identified to interact with the backbone of the functionally important residues Arg-35 and Trp-36. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-324) contains supplementary material, which is available to authorized users.",2013 Jul 18,"['Wang, Yi-Ting', 'Hsu, Hao-Jen', 'Fischer, Wolfgang B']",Springerplus,,,True
626267a319f0390205d0e2c5fa2c93e7402f274b,PMC,Expression of Recombinant Antibodies,http://dx.doi.org/10.3389/fimmu.2013.00217,PMC3725456,23908655,CC BY,"Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines, and transgenic plants are promising to obtain antibodies with “human-like” post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications.",2013 Jul 29,"['Frenzel, André', 'Hust, Michael', 'Schirrmann, Thomas']",Front Immunol,,,True
fc29089acf4b70c64a5a5e4ea64a318e8d52edbb,PMC,Transdifferentiation of MALME-3M and MCF-7 Cells toward Adipocyte-like Cells is Dependent on Clathrin-mediated Endocytosis,http://dx.doi.org/10.1186/2193-1801-1-44,PMC3725915,23961369,CC BY,"ABSTRACT: Enforced cell transdifferentiation of human cancer cells is a promising alternative to conventional chemotherapy. We previously identified albumin-associated lipid- and, more specifically, saturated fatty acid-induced transdifferentiation programs in human cancer cells (HCCLs). In this study, we further characterized the adipocyte-like cells, resulting from the transdifferentiation of human cancer cell lines MCF-7 and MALME-3M, and proposed a common mechanistic approach for these transdifferentiating programs. We showed the loss of pigmentation in MALME-3M cells treated with albumin-associated lipids, based on electron microscopic analysis, and the overexpression of perilipin 2 (PLIN2) by western blotting in MALME-3M and MCF-7 cells treated with unsaturated fatty acids. Comparing the gene expression profiles of naive melanoma MALME-3M cells and albumin-associated lipid-treated cells, based on RNA sequencing, we confirmed the transcriptional upregulation of some key adipogenic gene markers and also an alternative splicing of the adipogenic master regulator PPARG, that is probably related to the reported up regulated expression of the protein. Most importantly, these results also showed the upregulation of genes responsible for Clathrin (CLTC) and other adaptor-related proteins. An increase in CLTC expression in the transdifferentiated cells was confirmed by western blotting. Inactivation of CLTC by chlorpromazine (CHP), an inhibitor of CTLC mediated endocytosis (CME), and gene silencing by siRNAs, partially reversed the accumulation of neutral lipids observed in the transdifferentiated cells. These findings give a deeper insight into the phenotypic changes observed in HCCL to adipocyte-like transdifferentiation and point towards CME as a key pathway in distinct transdifferentiation programs. DISCLOSURES: Simon C and Aguilar-Gallardo C are co-inventors of the International Patent Application No. PCT/EP2011/004941 entitled “Methods for tumor treatment and adipogenesis differentiation”. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-1-44) contains supplementary material, which is available to authorized users.",2012 Oct 30,"['Carcel-Trullols, Jaime', 'Aguilar-Gallardo, Cristóbal', 'Garcia-Alcalde, Fernando', 'Pardo-Cea, Miguel Angel', 'Dopazo, Joaquin', 'Conesa, Ana', 'Simón, Carlos']",Springerplus,,,True
a11eb58857b227cdd846083d87304eef58b52ac2,PMC,Diverse activation of microglia by chemokine (C-C motif) ligand 2 overexpression in brain,http://dx.doi.org/10.1186/1742-2094-10-86,PMC3726363,23866683,CC BY,"BACKGROUND: The chemokine (C-C motif) ligand 2 (CCL2) is a monocyte chemoattractant protein that mediates macrophage recruitment and migration during peripheral and central nervous system (CNS) inflammation. METHODS: To determine the impact of CCL2 in inflammation in vivo and to elucidate the CCL2-induced polarization of activated brain microglia, we delivered CCL2 into the brains of wild-type mice via recombinant adeno-associated virus serotype 9 (rAAV-9) driven by the chicken β-actin promoter. We measured microglial activation using histological and chemical measurement and recruitment of monocytes using histology and flow cytometry. RESULTS: The overexpression of CCL2 in the CNS induced significant activation of brain resident microglia. CD45 and major histocompatibility complex class II immunoreactivity significantly increased at the sites of CCL2 administration. Histological characterization of the microglial phenotype revealed the elevation of “classically activated” microglial markers, such as calgranulin B and IL-1β, as well as markers associated with “alternative activation” of microglia, including YM1 and arginase 1. The protein expression profile in the hippocampus demonstrated markedly increased levels of IL-6, GM-CSF and eotaxin (CCL-11) in response to CCL2, but no changes in the levels of other cytokines, including TNF-α and IFN-γ. Moreover, real-time PCR analysis confirmed increases in mRNA levels of gene transcripts associated with neuroinflammation following CCL2 overexpression. Finally, we investigated the chemotactic properties of CCL2 in vivo by performing adoptive transfer of bone marrow–derived cells (BMDCs) isolated from donor mice that ubiquitously expressed green fluorescent protein. Flow cytometry and histological analyses indicated that BMDCs extravasated into brain parenchyma and colabeled with microglial markers. CONCLUSION: Taken together, our results suggest that CCL2 strongly activates resident microglia in the brain. Both pro- and anti-inflammatory activation of microglia were prominent, with no bias toward the M1 or M2 phenotype in the activated cells. As expected, CCL2 overexpression actively recruited circulating monocytes into the CNS. Thus, CCL2 expression in mouse brain induces microglial activation and represents an efficient method for recruitment of peripheral macrophages.",2013 Jul 17,"['Selenica, Maj-Linda B', 'Alvarez, Jennifer A', 'Nash, Kevin R', 'Lee, Daniel C', 'Cao, Chuanhai', 'Lin, Xiaoyang', 'Reid, Patrick', 'Mouton, Peter R', 'Morgan, Dave', 'Gordon, Marcia N']",J Neuroinflammation,,,True
58b271e61f06e148dd80d5dbf0c037118dcc9963,PMC,Changes in codon-pair bias of human immunodeficiency virus type 1 have profound effects on virus replication in cell culture,http://dx.doi.org/10.1186/1742-4690-10-78,PMC3726367,23885919,CC BY,"BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) has a biased nucleotide composition different from human genes. This raises the question of how evolution has chosen the nucleotide sequence of HIV-1 that is observed today, or to what extent the actual encoding contributes to virus replication capacity, evolvability and pathogenesis. Here, we applied the previously described synthetic attenuated virus engineering (SAVE) approach to HIV-1. RESULTS: Using synonymous codon pairs, we rationally recoded and codon pair–optimized and deoptimized different moieties of the HIV-1 gag and pol genes. Deoptimized viruses had significantly lower viral replication capacity in MT-4 and peripheral blood mononuclear cells (PBMCs). Varying degrees of ex vivo attenuation were obtained, depending upon both the specific deoptimized region and the number of deoptimized codons. A protease optimized virus carrying 38 synonymous mutations was not attenuated and displayed a replication capacity similar to that of the wild-type virus in MT-4 cells and PBMCs. Although attenuation is based on several tens of nucleotide changes, deoptimized HIV-1 reverted to wild-type virulence after serial passages in MT-4 cells. Remarkably, no reversion was observed in the optimized virus. CONCLUSION: These data demonstrate that SAVE is a useful strategy to phenotypically affect the replicative properties of HIV-1.",2013 Jul 25,"['Martrus, Gloria', 'Nevot, Maria', 'Andres, Cristina', 'Clotet, Bonaventura', 'Martinez, Miguel Angel']",Retrovirology,,,True
710dd69c07a692bbdcd7261bb4508cd9935556c6,PMC,Regulation of Coronaviral Poly(A) Tail Length during Infection,http://dx.doi.org/10.1371/journal.pone.0070548,PMC3726627,23923003,CC BY,"The positive-strand coronavirus genome of ~30 kilobase in length and subgenomic (sg) mRNAs of shorter lengths, are 5’ and 3’-co-terminal by virtue of a common 5’-capped leader and a common 3’-polyadenylated untranslated region. Here, by ligating head-to-tail viral RNAs from bovine coronavirus-infected cells and sequencing across the ligated junctions, it was learned that at the time of peak viral RNA synthesis [6 hours postinfection (hpi)] the 3’ poly(A) tail on genomic and sgmRNAs is ~65 nucleotides (nt) in length. Surprisingly, this length was found to vary throughout infection from ~45 nt immediately after virus entry (at 0 to 4 hpi) to ~65 nt later on (at 6 h to 9 hpi) and from ~65 nt (at 6 h to 9 hpi) to ~30 nt (at 120-144 hpi). With the same method, poly(U) sequences of the same lengths were simultaneously found on the ligated viral negative-strand RNAs. Functional analyses of poly(A) tail length on specific viral RNA species, furthermore, revealed that translation, in vivo, of RNAs with the longer poly(A) tail was enhanced over those with the shorter poly(A). Although the mechanisms by which the tail lengths vary is unknown, experimental results together suggest that the length of the poly(A) and poly(U) tails is regulated. One potential function of regulated poly(A) tail length might be that for the coronavirus genome a longer poly(A) favors translation. The regulation of coronavirus translation by poly(A) tail length resembles that during embryonal development suggesting there may be mechanistic parallels.",2013 Jul 29,"['Wu, Hung-Yi', 'Ke, Ting-Yung', 'Liao, Wei-Yu', 'Chang, Nai-Yun']",PLoS One,,,True
5d04b1e66045a858dd72847b88dcc6a280da3165,PMC,"Etiological analysis and predictive diagnostic model building of community-acquired pneumonia in adult outpatients in Beijing, China",http://dx.doi.org/10.1186/1471-2334-13-309,PMC3728139,23834931,CC BY,"BACKGROUND: Etiological epidemiology and diagnosis are important issues in adult community-acquired pneumonia (CAP), and identifying pathogens based on patient clinical features is especially a challenge. CAP-associated main pathogens in adults include viruses as well as bacteria. However, large-scale epidemiological investigations of adult viral CAP in China are still lacking. In this study, we analyzed the etiology of adult CAP in Beijing, China and constructed diagnostic models based on combinations of patient clinical factors. METHODS: A multicenter cohort was established with 500 adult CAP outpatients enrolled in Beijing between November 2010 to October 2011. Multiplex and quantitative real-time fluorescence PCR were used to detect 15 respiratory viruses and mycoplasma pneumoniae, respectively. Bacteria were detected with culture and enzyme immunoassay of the Streptococcus pneumoniae urinary antigen. Univariate analysis, multivariate analysis, discriminatory analysis and Receiver Operating Characteristic (ROC) curves were used to build predictive models for etiological diagnosis of adult CAP. RESULTS: Pathogens were detected in 54.2% (271/500) of study patients. Viruses accounted for 36.4% (182/500), mycoplasma pneumoniae for 18.0% (90/500) and bacteria for 14.4% (72/500) of the cases. In 182 of the patients with viruses, 219 virus strains were detected, including 166 single and 53 mixed viral infections. Influenza A virus represented the greatest proportion with 42.0% (92/219) and 9.1% (20/219) in single and mixed viral infections, respectively. Factors selected for the predictive etiological diagnostic model of viral CAP included cough, dyspnea, absence of chest pain and white blood cell count (4.0-10.0) × 10(9)/L, and those of mycoplasma pneumoniae CAP were being younger than 45 years old and the absence of a coexisting disease. However, these models showed low accuracy levels for etiological diagnosis (areas under ROC curve for virus and mycoplasma pneumoniae were both 0.61, P < 0.05). CONCLUSIONS: Greater consideration should be given to viral and mycoplasma pneumoniae infections in adult CAP outpatients. While predictive etiological diagnostic models of viral and mycoplasma pneumoniae based on combinations of demographic and clinical factors may provide indications of etiology, diagnostic confirmation of CAP remains dependent on laboratory pathogen test results.",2013 Jul 9,"['Liu, Ya-Fen', 'Gao, Yan', 'Chen, Mei-Fang', 'Cao, Bin', 'Yang, Xiao-Hua', 'Wei, Lai']",BMC Infect Dis,,,True
c4e5c3ffe90100931729abab4aa1155d8c145816,PMC,Protective Efficacy of VP1-Specific Neutralizing Antibody Associated with a Reduction of Viral Load and Pro-Inflammatory Cytokines in Human SCARB2-Transgenic Mice,http://dx.doi.org/10.1371/journal.pone.0069858,PMC3728341,23936115,CC BY,"Hand-foot-mouth diseases (HFMD) caused by enterovirus 71 (EV71) and coxsackievirus 16 (CVA16) in children have now become a severe public health issue in the Asian-Pacific region. Recently we have successfully developed transgenic mice expressing human scavenger receptor class B member 2 (hSCARB2, a receptor of EV71 and CVA16) as an animal model for evaluating the pathogenesis of enterovirus infections. In this study, hSCARB2-transgenic mice were used to investigate the efficacy conferred by a previously described EV71 neutralizing antibody, N3. A single injection of N3 effectively inhibited the HFMD-like skin scurfs in mice pre-infected with clinical isolate of EV71 E59 (B4 genotype) or prevented severe limb paralysis and death in mice pre-inoculated with 5746 (C2 genotype). This protection was correlated with remarkable reduction of viral loads in the brain, spinal cord and limb muscles. Accumulated viral loads and the associated pro-inflammatory cytokines were all reduced. The protective efficacy of N3 was not observed in animals challenged with CVA16. This could be due to dissimilarity sequences of the neutralizing epitope found in CVA16. These results indicate N3 could be useful in treating severe EV71 infections and the hSCARB2-transgenic mouse could be used to evaluate the protective efficacy of potential anti-enterovirus agent candidates.",2013 Jul 30,"['Chang, Hsuen-Wen', 'Lin, Yi-Wen', 'Ho, Hui-Min', 'Lin, Min-Han', 'Liu, Chia-Chyi', 'Shao, Hsiao-Yun', 'Chong, Pele', 'Sia, Charles', 'Chow, Yen-Hung']",PLoS One,,,True
943491914a5f52c713070accbde7e0e868771e91,PMC,Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies,http://dx.doi.org/10.1371/journal.pone.0069649,PMC3729563,23936066,CC BY,"Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN) or the intrapulmonary (IPL) route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses.",2013 Jul 31,"['Liu, Heng', 'Patil, Harshad P.', 'de Vries-Idema, Jacqueline', 'Wilschut, Jan', 'Huckriede, Anke']",PLoS One,,,True
0e5ca6286111f518f4d41267587324c92a902aa2,PMC,Arenavirus budding resulting from viral-protein-associated cell membrane curvature,http://dx.doi.org/10.1098/rsif.2013.0403,PMC3730687,23864502,CC BY,"Viral replication occurs within cells, with release (and onward infection) primarily achieved through two alternative mechanisms: lysis, in which virions emerge as the infected cell dies and bursts open; or budding, in which virions emerge gradually from a still living cell by appropriating a small part of the cell membrane. Virus budding is a poorly understood process that challenges current models of vesicle formation. Here, a plausible mechanism for arenavirus budding is presented, building on recent evidence that viral proteins embed in the inner lipid layer of the cell membrane. Experimental results confirm that viral protein is associated with increased membrane curvature, whereas a mathematical model is used to show that localized increases in curvature alone are sufficient to generate viral buds. The magnitude of the protein-induced curvature is calculated from the size of the amphipathic region hypothetically removed from the inner membrane as a result of translation, with a change in membrane stiffness estimated from observed differences in virion deformation as a result of protein depletion. Numerical results are based on experimental data and estimates for three arenaviruses, but the mechanisms described are more broadly applicable. The hypothesized mechanism is shown to be sufficient to generate spontaneous budding that matches well both qualitatively and quantitatively with experimental observations.",2013 Sep 6,"['Schley, David', 'Whittaker, Robert J.', 'Neuman, Benjamin W.']",J R Soc Interface,,,True
492ae848b7e2b20047ac406af1c7712ea6255461,PMC,Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent Varicella-Zoster Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1003512,PMC3731237,23935496,CC0,"Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.",2013 Aug 1,"['Goodwin, Thomas J.', 'McCarthy, Maureen', 'Osterrieder, Nikolaus', 'Cohrs, Randall J.', 'Kaufer, Benedikt B.']",PLoS Pathog,,,True
0080d3bd9fb92e022c27715c2d1249042aa998b8,PMC,Rational Design of a Live Attenuated Dengue Vaccine: 2′-O-Methyltransferase Mutants Are Highly Attenuated and Immunogenic in Mice and Macaques,http://dx.doi.org/10.1371/journal.ppat.1003521,PMC3731252,23935499,CC BY,"Dengue virus is transmitted by Aedes mosquitoes and infects at least 100 million people every year. Progressive urbanization in Asia and South-Central America and the geographic expansion of Aedes mosquito habitats have accelerated the global spread of dengue, resulting in a continuously increasing number of cases. A cost-effective, safe vaccine conferring protection with ideally a single injection could stop dengue transmission. Current vaccine candidates require several booster injections or do not provide protection against all four serotypes. Here we demonstrate that dengue virus mutants lacking 2′-O-methyltransferase activity are highly sensitive to type I IFN inhibition. The mutant viruses are attenuated in mice and rhesus monkeys and elicit a strong adaptive immune response. Monkeys immunized with a single dose of 2′-O-methyltransferase mutant virus showed 100% sero-conversion even when a dose as low as 1,000 plaque forming units was administrated. Animals were fully protected against a homologous challenge. Furthermore, mosquitoes feeding on blood containing the mutant virus were not infected, whereas those feeding on blood containing wild-type virus were infected and thus able to transmit it. These results show the potential of 2′-O-methyltransferase mutant virus as a safe, rationally designed dengue vaccine that restrains itself due to the increased susceptibility to the host's innate immune response.",2013 Aug 1,"['Züst, Roland', 'Dong, Hongping', 'Li, Xiao-Feng', 'Chang, David C.', 'Zhang, Bo', 'Balakrishnan, Thavamalar', 'Toh, Ying-Xiu', 'Jiang, Tao', 'Li, Shi-Hua', 'Deng, Yong-Qiang', 'Ellis, Brett R.', 'Ellis, Esther M.', 'Poidinger, Michael', 'Zolezzi, Francesca', 'Qin, Cheng-Feng', 'Shi, Pei-Yong', 'Fink, Katja']",PLoS Pathog,,,True
088571fa032ef5eb915d17b62e106a698a301f2c,PMC,Characterization of Synthetic Chikungunya Viruses Based on the Consensus Sequence of Recent E1-226V Isolates,http://dx.doi.org/10.1371/journal.pone.0071047,PMC3731263,23936484,CC BY,"Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that re-emerged in 2004 and has caused massive outbreaks in recent years. The lack of a licensed vaccine or treatment options emphasize the need to obtain more insight into the viral life cycle and CHIKV-host interactions. Infectious cDNA clones are important tools for such studies, and for mechanism of action studies on antiviral compounds. Existing CHIKV cDNA clones are based on a single genome from an individual clinical isolate, which is expected to have evolved specific characteristics in response to the host environment, and possibly also during subsequent cell culture passaging. To obtain a virus expected to have the general characteristics of the recent E1-226V CHIKV isolates, we have constructed a new CHIKV full-length cDNA clone, CHIKV LS3, based on the consensus sequence of their aligned genomes. Here we report the characterization of this synthetic virus and a green fluorescent protein-expressing variant (CHIKV LS3-GFP). Their characteristics were compared to those of natural strain ITA07-RA1, which was isolated during the 2007 outbreak in Italy. In cell culture the synthetic viruses displayed phenotypes comparable to the natural isolate, and in a mouse model they caused lethal infections that were indistinguishable from infections with a natural strain. Compared to ITA07-RA1 and clinical isolate NL10/152, the synthetic viruses displayed similar sensitivities to several antiviral compounds. 3-deaza-adenosine was identified as a new inhibitor of CHIKV replication. Cyclosporin A had no effect on CHIKV replication, suggesting that cyclophilins -opposite to what was found for other +RNA viruses- do not play an essential role in CHIKV replication. The characterization of the consensus sequence-based synthetic viruses and their comparison to natural isolates demonstrated that CHIKV LS3 and LS3-GFP are suitable and representative tools to study CHIKV-host interactions, screen for antiviral compounds and unravel their mode of action.",2013 Aug 1,"['Scholte, Florine E. M.', 'Tas, Ali', 'Martina, Byron E. E.', 'Cordioli, Paolo', 'Narayanan, Krishna', 'Makino, Shinji', 'Snijder, Eric J.', 'van Hemert, Martijn J.']",PLoS One,,,True
a2bcb2cb93937aaa45834b4a1fa568334c58ae96,PMC,Characterization of Synthetic Chikungunya Viruses Based on the Consensus Sequence of Recent E1-226V Isolates,http://dx.doi.org/10.1371/journal.pone.0071047,PMC3731263,23936484,CC BY,"Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that re-emerged in 2004 and has caused massive outbreaks in recent years. The lack of a licensed vaccine or treatment options emphasize the need to obtain more insight into the viral life cycle and CHIKV-host interactions. Infectious cDNA clones are important tools for such studies, and for mechanism of action studies on antiviral compounds. Existing CHIKV cDNA clones are based on a single genome from an individual clinical isolate, which is expected to have evolved specific characteristics in response to the host environment, and possibly also during subsequent cell culture passaging. To obtain a virus expected to have the general characteristics of the recent E1-226V CHIKV isolates, we have constructed a new CHIKV full-length cDNA clone, CHIKV LS3, based on the consensus sequence of their aligned genomes. Here we report the characterization of this synthetic virus and a green fluorescent protein-expressing variant (CHIKV LS3-GFP). Their characteristics were compared to those of natural strain ITA07-RA1, which was isolated during the 2007 outbreak in Italy. In cell culture the synthetic viruses displayed phenotypes comparable to the natural isolate, and in a mouse model they caused lethal infections that were indistinguishable from infections with a natural strain. Compared to ITA07-RA1 and clinical isolate NL10/152, the synthetic viruses displayed similar sensitivities to several antiviral compounds. 3-deaza-adenosine was identified as a new inhibitor of CHIKV replication. Cyclosporin A had no effect on CHIKV replication, suggesting that cyclophilins -opposite to what was found for other +RNA viruses- do not play an essential role in CHIKV replication. The characterization of the consensus sequence-based synthetic viruses and their comparison to natural isolates demonstrated that CHIKV LS3 and LS3-GFP are suitable and representative tools to study CHIKV-host interactions, screen for antiviral compounds and unravel their mode of action.",2013 Aug 1,"['Scholte, Florine E. M.', 'Tas, Ali', 'Martina, Byron E. E.', 'Cordioli, Paolo', 'Narayanan, Krishna', 'Makino, Shinji', 'Snijder, Eric J.', 'van Hemert, Martijn J.']",PLoS One,,,False
baa8420ed8f9d0dc7ba81b519eda2c3fe91291b8,PMC,The First Transmembrane Domain of Lipid Phosphatase SAC1 Promotes Golgi Localization,http://dx.doi.org/10.1371/journal.pone.0071112,PMC3731292,23936490,CC BY,"The lipid phosphatase Sac1 cycles between endoplasmic reticulum and cisternal Golgi compartments. In proliferating mammalian cells, a canonical dilysine motif at the C-terminus of Sac1 is required for coatomer complex-I (COP-I)-binding and continuous retrieval to the ER. Starvation triggers accumulation of Sac1 at the Golgi. The mechanism responsible for Golgi retention of Sac1 is unknown. Here we show that the first of the two transmembrane regions in human SAC1 (TM1) functions in Golgi localization. A minimal construct containing only TM1 and the adjacent flanking sequences is concentrated at the Golgi. Transplanting TM1 into transferrin receptor 2 (TfR2) induces Golgi accumulation of this normally plasma membrane and endosomal protein, indicating that TM1 is sufficient for Golgi localization. In addition, we determined that the N-terminal cytoplasmic domain of SAC1 also promotes Golgi localization, even when TM1 is mutated or absent. We conclude that the distribution of SAC1 within the Golgi is controlled via both passive membrane thickness-dependent partitioning of TM1 and a retention mechanism that requires the N-terminal cytoplasmic region.",2013 Aug 1,"['Wang, Jinzhi', 'Chen, Juxing', 'Enns, Caroline A.', 'Mayinger, Peter']",PLoS One,,,True
f81ae57f3c989bf53683a523da0a1799ebd19862,PMC,Rapid and Sensitive Detection of Novel Avian-Origin Influenza A (H7N9) Virus by Reverse Transcription Loop-Mediated Isothermal Amplification Combined with a Lateral-Flow Device,http://dx.doi.org/10.1371/journal.pone.0069941,PMC3731295,23936359,CC BY,"A severe disease in humans caused by a novel avian-origin influenza A (H7N9) virus emerged in China recently, which has caused at least 128 cases and 26 deaths. Rapid detection of the novel H7N9 virus is urgently needed to differentiate the disease from other infections, and to facilitate infection control as well as epidemiologic investigations. In this study, a reverse transcription loop-mediated isothermal amplification combined with a lateral flow device (RT-LAMP-LFD) assay to rapidly detect H7N9 virus was developed and evaluated. The RT-LAMP primers were designed to target the haemagglutinin (HA) and neuraminidase (NA) genes of H7N9 virus. Results of 10-fold dilution series assays showed that analysis of RT-LAMP products by the LFD method was as sensitive as real-time turbidity detection, and that the analytic sensitivities of the HA and NA RT-LAMP assays were both 10 copies of synthetic RNA. Furthermore, both the assays showed 100% clinical specificity for identification of H7N9 virus. The performance characteristics of the RT-LAMP-LFD assay were evaluated with 80 clinical specimens collected from suspected H7N9 patients. The NA RT-LAMP-LFD assay was more sensitive than real time RT-PCR assay. Compared with a combination of virus culture and real-time RT-PCR, the sensitivity, specificity, positive predictive value, and negative predictive value of the RT-LAMP-LFD assay were all 100%. Overall, The RT-LAMP-LFD assay established in this study can be used as a reliable method for early diagnosis of the avian-origin influenza A (H7N9) virus infection.",2013 Aug 1,"['Ge, Yiyue', 'Wu, Bin', 'Qi, Xian', 'Zhao, Kangchen', 'Guo, Xiling', 'Zhu, Yefei', 'Qi, Yuhua', 'Shi, Zhiyang', 'Zhou, Minghao', 'Wang, Hua', 'Cui, Lunbiao']",PLoS One,,,True
5eb39003823f5339573f8f9ed82eaf7763feda68,PMC,Manipulation of the Porcine Epidemic Diarrhea Virus Genome Using Targeted RNA Recombination,http://dx.doi.org/10.1371/journal.pone.0069997,PMC3732256,23936367,CC BY,"Porcine epidemic diarrhea virus (PEDV) causes severe economic losses in the swine industry in China and other Asian countries. Infection usually leads to an acute, often lethal diarrhea in piglets. Despite the impact of the disease, no system is yet available to manipulate the viral genome which has severely hampered research on this virus until today. We have established a reverse genetics system for PEDV based on targeted RNA recombination that allows the modification of the 3′-end of the viral genome, which encodes the structural proteins and the ORF3 protein. Using this system, we deleted the ORF3 gene entirely from the viral genome and showed that the ORF3 protein is not essential for replication of the virus in vitro. In addition, we inserted heterologous genes (i.e. the GFP and Renilla luciferase genes) at two positions in the viral genome, either as an extra expression cassette or as a replacement for the ORF3 gene. We demonstrated the expression of both GFP and Renilla luciferase as well as the application of these viruses by establishing a convenient and rapid virus neutralization assay. The new PEDV reverse genetics system will enable functional studies of the structural proteins and the accessory ORF3 protein and will allow the rational design and development of next generation PEDV vaccines.",2013 Aug 2,"['Li, Chunhua', 'Li, Zhen', 'Zou, Yong', 'Wicht, Oliver', 'van Kuppeveld, Frank J. M.', 'Rottier, Peter J. M.', 'Bosch, Berend Jan']",PLoS One,,,True
2a7617954fb5dc66e2d7d62b1e5ea2c54f4e02ce,PMC,Modulation of airway epithelial cell functions by Pidotimod: NF-kB cytoplasmatic expression and its nuclear translocation are associated with an increased TLR-2 expression,http://dx.doi.org/10.1186/1824-7288-39-29,PMC3733658,23663325,CC BY,"BACKGROUND: Recurrent respiratory infections are one of the most important causes of morbidity in childhood. When immune functions are still largely immature, the airway epithelium plays a primary defensive role since, besides providing a physical barrier, it is also involved in the innate and the adaptive immune responses. A study was therefore designed to evaluate in vitro whether pidotimod, a synthetic dipeptide able to stimulate the inflammatory and immune effector cells, could activate bronchial epithelial cell functions involved in response to infections. METHODS: BEAS-2B cell line (human bronchial epithelial cells infected with a replication-defective Adenovirus 12-SV40 virus hybrid) were cultured in the presence of pidotimod, with or without tumor necrosis factor (TNF)-α or zymosan to assess: a) intercellular adhesion molecule (ICAM)-1 expression, by flow cytometry; b) toll-like receptor (TLR)-2 expression and production, by immunofluorescence flow cytometry and western blotting; d) interleukin (IL)-8 release, by enzyme-linked immunosorbent assay (ELISA); e) activated extracellular-signal-regulated kinase (ERK1/2) phosphorylation and nuclear factor-kappa B (NF-kB) activation, by western blotting. RESULTS: The constitutive expression of ICAM-1 and IL-8 release were significant up-regulated by TNF-α (ICAM-1) and by TNF-α and zymosan (IL-8), but not by pidotimod. In contrast, an increased TLR-2 expression was found after exposure to pidotimod 10 and 100 μg/ml (p < 0.05) and to the association pidotimod 100 μg/ml + TNF-α (p < 0.05). Western blot analysis substantiated that the constitutive TLR-2 expression was significantly increased after exposure to all the stimuli. Finally, while a remarkable inhibition of TNF-α -induced ERK1/2 phosphorylation was observed in the presence of pidotimod, both TNF-α and pidotimod were effective in inducing NF-kB protein expression in the cytoplasm and its nuclear translocation. CONCLUSION: Through different effects on ERK1/2 and NF-kB, pidotimod was able to increase the expression of TLR-2 proteins, surface molecules involved in the initiation of the innate response to infectious stimuli. The lack of effect on ICAM-1 expression, the receptor for rhinovirus, and on IL-8 release, the potent chemotactic factor for neutrophils (that are already present in sites of infection), may represent protective functions. If confirmed in vivo, these activities may, at least in part, clarify the mechanism of action of this molecule at airway level.",2013 May 10,"['Carta, Sonia', 'Silvestri, Michela', 'Rossi, Giovanni A']",Ital J Pediatr,,,True
77c5a33cacec66e3eecf748902a04cd245df6e0f,PMC,TNF-α Acts as an Immunoregulator in the Mouse Brain by Reducing the Incidence of Severe Disease Following Japanese Encephalitis Virus Infection,http://dx.doi.org/10.1371/journal.pone.0071643,PMC3733918,23940775,CC BY,"Japanese encephalitis virus (JEV) causes acute central nervous system (CNS) disease in humans, in whom the clinical symptoms vary from febrile illness to meningitis and encephalitis. However, the mechanism of severe encephalitis has not been fully elucidated. In this study, using a mouse model, we investigated the pathogenetic mechanisms that correlate with fatal JEV infection. Following extraneural infection with the JaOArS982 strain of JEV, infected mice exhibited clinical signs ranging from mild to fatal outcome. Comparison of the pathogenetic response between severe and mild cases of JaOArS982-infected mice revealed increased levels of TNF-α in the brains of severe cases. However, unexpectedly, the mortality rate of TNF-α KO mice was significantly increased compared with that of WT mice, indicating that TNF-α plays a protective role against fatal infection. Interestingly, there were no significant differences of viral load in the CNS between WT and TNF-α KO mice. However, exaggerated inflammatory responses were observed in the CNS of TNF-α KO mice. Although these observations were also obtained in IL-10 KO mice, the mortality and enhanced inflammatory responses were more pronounced in TNF-α KO mice. Our findings therefore provide the first evidence that TNF-α has an immunoregulatory effect on pro-inflammatory cytokines in the CNS during JEV infection and consequently protects the animals from fatal disease. Thus, we propose that the increased level of TNF-α in severe cases was the result of severe disease, and secondly that immunopathological effects contribute to severe neuronal degeneration resulting in fatal disease. In future, further elucidation of the immunoregulatory mechanism of TNF-α will be an important priority to enable the development of effective treatment strategies for Japanese encephalitis.",2013 Aug 5,"['Hayasaka, Daisuke', 'Shirai, Kenji', 'Aoki, Kotaro', 'Nagata, Noriyo', 'Simantini, Dash Sima', 'Kitaura, Kazutaka', 'Takamatsu, Yuki', 'Gould, Ernest', 'Suzuki, Ryuji', 'Morita, Kouichi']",PLoS One,,,True
789ab4d7c1e859c96e68389e03290355c30a03a7,PMC,Identification of cellular proteome using two-dimensional difference gel electrophoresis in ST cells infected with transmissible gastroenteritis coronavirus,http://dx.doi.org/10.1186/1477-5956-11-31,PMC3734006,23855489,CC BY,"BACKGROUND: Transmissible gastroenteritis coronavirus (TGEV) is an enteropathogenic coronavirus that causes diarrhea in pigs, which is correlated with high morbidity and mortality in suckling piglets. Information remains limited about the comparative protein expression of host cells in response to TGEV infection. In this study, cellular protein response to TGEV infection in swine testes (ST) cells was analyzed, using the proteomic method of two-dimensional difference gel electrophoresis (2D DIGE) coupled with MALDI-TOF-TOF/MS identification. RESULTS: 33 differentially expressed protein spots, of which 23 were up-regulated and 10 were down-regulated were identified. All the protein spots were successfully identified. The identified proteins were involved in the regulation of essential processes such as cellular structure and integrity, RNA processing, protein biosynthesis and modification, vesicle transport, signal transduction, and the mitochondrial pathway. Western blot analysis was used to validate the changes of alpha tubulin, keratin 19, and prohibitin during TGEV infection. CONCLUSIONS: To our knowledge, we have performed the first analysis of the proteomic changes in host cell during TGEV infection. 17 altered cellular proteins that differentially expressed in TGEV infection were identified. The present study provides protein-related information that should be useful for understanding the host cell response to TGEV infection and the underlying mechanism of TGEV replication and pathogenicity.",2013 Jul 16,"['Zhang, Xin', 'Shi, Hong-Yan', 'Chen, Jian-Fei', 'Shi, Da', 'Lang, Hong-Wu', 'Wang, Zhong-Tian', 'Feng, Li']",Proteome Sci,,,True
ee8483f8f2cc5fe38be4e565eae3af9d0bb8220b,PMC,"Design, Synthesis, Evaluation and Thermodynamics of 1-Substituted Pyridylimidazo[1,5-a]Pyridine Derivatives as Cysteine Protease Inhibitors",http://dx.doi.org/10.1371/journal.pone.0069982,PMC3734177,23940536,CC BY,"Targeting papain family cysteine proteases is one of the novel strategies in the development of chemotherapy for a number of diseases. Novel cysteine protease inhibitors derived from 1-pyridylimidazo[1,5-a]pyridine representing pharmacologically important class of compounds are being reported here for the first time. The derivatives were initially designed and screened in silico by molecular docking studies against papain to explore the possible mode of action. The molecular interaction between the compounds and cysteine protease (papain) was found to be very similar to the interactions observed with the respective epoxide inhibitor (E-64c) of papain. Subsequently, compounds were synthesized to validate their efficacy in wet lab experiments. When characterized kinetically, these compounds show their K(i) and IC(50) values in the range of 13.75 to 99.30 µM and 13.40 to 96.50 µM, respectively. The thermodynamics studies suggest their binding with papain hydrophobically and entropically driven. These inhibitors also inhibit the growth of clinically important different types of Gram positive and Gram negative bacteria having MIC(50) values in the range of 0.6–1.4 µg/ml. Based on Lipinski’s rule of Five, we also propose these compounds as potent antibacterial prodrugs. The most active antibacterial compound was found to be 1-(2-pyridyl)-3-(2-hydroxyphenyl)imidazo[1,5-a]pyridine (3a).",2013 Aug 5,"['Khan, Mohd Sajid', 'Baig, Mohd Hassan', 'Ahmad, Saheem', 'Siddiqui, Shapi Ahmad', 'Srivastava, Ashwini Kumar', 'Srinivasan, Kumar Venkatraman', 'Ansari, Irfan A.']",PLoS One,,,True
5314aaa04b14fdbb926bc8eeb0826eedee66dadc,PMC,Understanding and Managing Zoonotic Risk in the New Livestock Industries,http://dx.doi.org/10.1289/ehp.1206001,PMC3734490,23665854,CC0,"Background: In many parts of the world, livestock production is undergoing a process of rapid intensification. The health implications of this development are uncertain. Intensification creates cheaper products, allowing more people to access animal-based foods. However, some practices associated with intensification may contribute to zoonotic disease emergence and spread: for example, the sustained use of antibiotics, concentration of animals in confined units, and long distances and frequent movement of livestock. Objectives: Here we present the diverse range of ecological, biological, and socioeconomic factors likely to enhance or reduce zoonotic risk, and identify ways in which a comprehensive risk analysis may be conducted by using an interdisciplinary approach. We also offer a conceptual framework to guide systematic research on this problem. Discussion: We recommend that interdisciplinary work on zoonotic risk should take into account the complexity of risk environments, rather than limiting studies to simple linear causal relations between risk drivers and disease emergence and/or spread. In addition, interdisciplinary integration is needed at different levels of analysis, from the study of risk environments to the identification of policy options for risk management. Conclusion: Given rapid changes in livestock production systems and their potential health implications at the local and global level, the problem we analyze here is of great importance for environmental health and development. Although we offer a systematic interdisciplinary approach to understand and address these implications, we recognize that further research is needed to clarify methodological and practical questions arising from the integration of the natural and social sciences.",2013 Aug 10,"['Liverani, Marco', 'Waage, Jeff', 'Barnett, Tony', 'Pfeiffer, Dirk U.', 'Rushton, Jonathan', 'Rudge, James W.', 'Loevinsohn, Michael E.', 'Scoones, Ian', 'Smith, Richard D.', 'Cooper, Ben S.', 'White, Lisa J.', 'Goh, Shan', 'Horby, Peter', 'Wren, Brendan', 'Gundogdu, Ozan', 'Woods, Abigail', 'Coker, Richard J.']",Environ Health Perspect,,,True
09561ed721369a7a9e077f7bea9022499c12b13d,PMC,Estimating the reproductive number in the presence of spatial heterogeneity of transmission patterns,http://dx.doi.org/10.1186/1476-072X-12-35,PMC3735474,23890514,CC BY,"BACKGROUND: Estimates of parameters for disease transmission in large-scale infectious disease outbreaks are often obtained to represent large groups of people, providing an average over a potentially very diverse area. For control measures to be more effective, a measure of the heterogeneity of the parameters is desirable. METHODS: We propose a novel extension of a network-based approach to estimating the reproductive number. With this we can incorporate spatial and/or demographic information through a similarity matrix. We apply this to the 2009 Influenza pandemic in South Africa to understand the spatial variability across provinces. We explore the use of five similarity matrices to illustrate their impact on the subsequent epidemic parameter estimates. RESULTS: When treating South Africa as a single entity with homogeneous transmission characteristics across the country, the basic reproductive number, R(0), (and imputation range) is 1.33 (1.31, 1.36). When fitting a new model for each province with no inter-province connections this estimate varies little (1.23-1.37). Using the proposed method with any of the four similarity measures yields an overall R(0) that varies little across the four new models (1.33 to 1.34). However, when allowed to vary across provinces, the estimated R(0) is greater than one consistently in only two of the nine provinces, the most densely populated provinces of Gauteng and Western Cape. CONCLUSIONS: Our results suggest that the spatial heterogeneity of influenza transmission was compelling in South Africa during the 2009 pandemic. This variability makes a qualitative difference in our understanding of the epidemic. While the cause of this fluctuation might be partially due to reporting differences, there is substantial evidence to warrant further investigation.",2013 Jul 26,"['White, Laura F', 'Archer, Brett', 'Pagano, Marcello']",Int J Health Geogr,,,True
ea2a30291a27a30b944a84050fff8bdf64e94130,PMC,Smallpox Still Haunts Scientists: Results of a Questionnaire-Based Inquiry on the Views of Health Care and Life Science Experts and Students on Preserving the Remaining Variola Virus Stocks,http://dx.doi.org/10.1155/2013/672813,PMC3736420,23970838,CC BY,"The World Health Organization (WHO) declared eradication of the dreadful disease “smallpox” in 1980. Though the disease has died down, the causative virus “variola” has not, as it has been well preserved in two high security laboratories—one in USA and another in Russia. The debate on whether the remaining stocks of the smallpox virus should be destroyed or not is ongoing, and the World Health Assembly (WHA) in 2011 has decided to postpone the review on this debate to the 67th WHA in 2014. A short questionnaire-based inquiry was organized during a one-day stem cell meeting to explore the views of various health care and life science specialists especially students on this aspect. Among the 200 participants of the meeting, only 66 had answered the questionnaire. 60.6% of participants who responded to the questionnaire were for preserving the virus for future reference, while 36.4% of the participants were for destroying the virus considering the magnitude with which it killed millions. However, 3% of the respondents were not able to decide on any verdict. Therefore, this inquiry expresses the view that “what we cannot create, we do not have the right to destroy.”",2013 Jul 22,"['Srinivasan, Thangavelu', 'Dedeepiya, Vidyasagar Devaprasad', 'John, Sudhakar', 'Senthilkumar, Rajappa', 'Reena, Helen C.', 'Rajendran, Paramasivam', 'Balamurugan, Madasamy', 'Kurosawa, Gene', 'Iwasaki, Masaru', 'Preethy, Senthilkumar', 'Abraham, Samuel J. K.']",ScientificWorldJournal,,,True
a7344a564121bf1e3f995911e78c17b1b2aee903,PMC,A Systematic Analysis of Host Factors Reveals a Med23-Interferon-λ Regulatory Axis against Herpes Simplex Virus Type 1 Replication,http://dx.doi.org/10.1371/journal.ppat.1003514,PMC3738494,23950709,CC BY,"Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome.",2013 Aug 8,"['Griffiths, Samantha J.', 'Koegl, Manfred', 'Boutell, Chris', 'Zenner, Helen L.', 'Crump, Colin M.', 'Pica, Francesca', 'Gonzalez, Orland', 'Friedel, Caroline C.', 'Barry, Gerald', 'Martin, Kim', 'Craigon, Marie H.', 'Chen, Rui', 'Kaza, Lakshmi N.', 'Fossum, Even', 'Fazakerley, John K.', 'Efstathiou, Stacey', 'Volpi, Antonio', 'Zimmer, Ralf', 'Ghazal, Peter', 'Haas, Jürgen']",PLoS Pathog,,,True
da309b7481a117d1aad2212d42ad3b7c0c68abf3,PMC,Crystal Structure of the Full-Length Japanese Encephalitis Virus NS5 Reveals a Conserved Methyltransferase-Polymerase Interface,http://dx.doi.org/10.1371/journal.ppat.1003549,PMC3738499,23950717,CC BY,"The flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal ≈265 residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part. One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. The structure completes the vision for polymerase motifs F and G, and depicts defined intra-molecular interactions between RdRP and MTase. Key hydrophobic residues in the RdRP-MTase interface are highly conserved in flaviviruses, indicating the biological relevance of the observed conformation. Our work paves the way for further dissection of the inter-regulations of the essential enzymatic activities of NS5 and exploration of possible other conformations of NS5 under different circumstances.",2013 Aug 8,"['Lu, Guoliang', 'Gong, Peng']",PLoS Pathog,,,True
2d1c0935153f0c1139529c1c05373504028abd4a,PMC,Crystal Structure of the Full-Length Japanese Encephalitis Virus NS5 Reveals a Conserved Methyltransferase-Polymerase Interface,http://dx.doi.org/10.1371/journal.ppat.1003549,PMC3738499,23950717,CC BY,"The flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal ≈265 residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part. One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. The structure completes the vision for polymerase motifs F and G, and depicts defined intra-molecular interactions between RdRP and MTase. Key hydrophobic residues in the RdRP-MTase interface are highly conserved in flaviviruses, indicating the biological relevance of the observed conformation. Our work paves the way for further dissection of the inter-regulations of the essential enzymatic activities of NS5 and exploration of possible other conformations of NS5 under different circumstances.",2013 Aug 8,"['Lu, Guoliang', 'Gong, Peng']",PLoS Pathog,,,True
7763fdd2366c612dc01aaf0173ea6bb8f1ed0bf9,PMC,Complete Genome Sequence of Porcine Epidemic Diarrhea Virus Strain USA/Colorado/2013 from the United States,http://dx.doi.org/10.1128/genomeA.00555-13,PMC3738886,23929470,CC BY,"Porcine epidemic diarrhea virus (PEDV) is newly emerging in the United States. PEDV strain USA/Colorado/2013 (CO/13) was obtained from a 7-day-old piglet with severe diarrhea, and the complete genome was sequenced to further study the PEDV outbreak in the United States.",2013 Aug 8,"['Marthaler, Douglas', 'Jiang, Yin', 'Otterson, Tracy', 'Goyal, Sagar', 'Rossow, Kurt', 'Collins, James']",Genome Announc,,,True
33542ce3cc964e6621e0ce35fedd41b34367de76,PMC,Histone Deacetylases in Herpesvirus Replication and Virus-Stimulated Host Defense,http://dx.doi.org/10.3390/v5071607,PMC3738950,23807710,CC BY,"Emerging evidence highlights a critical role for protein acetylation during herpesvirus infection. As prominent modulators of protein acetylation, histone deacetylases (HDACs) are essential transcriptional and epigenetic regulators. Not surprisingly, viruses have evolved a wide array of mechanisms to subvert HDAC functions. Here, we review the mechanisms underlying HDAC regulation during herpesvirus infection. We next discuss the roles of acetylation in host defense against herpesvirus infection. Finally, we provide a perspective on the contribution of current mass spectrometry-based “omic” technologies to infectious disease research, offering a systems biology view of infection.",2013 Jun 27,"['Guise, Amanda J.', 'Budayeva, Hanna G.', 'Diner, Benjamin A.', 'Cristea, Ileana M.']",Viruses,,,True
860ddc48c73d4757ceb161a9b43e73138b6b94a4,PMC,Cyclophilins as Modulators of Viral Replication,http://dx.doi.org/10.3390/v5071684,PMC3738956,23852270,CC BY,"Cyclophilins are peptidyl‐prolyl cis/trans isomerases important in the proper folding of certain proteins. Mounting evidence supports varied roles of cyclophilins, either positive or negative, in the life cycles of diverse viruses, but the nature and mechanisms of these roles are yet to be defined. The potential for cyclophilins to serve as a drug target for antiviral therapy is evidenced by the success of non-immunosuppressive cyclophilin inhibitors (CPIs), including Alisporivir, in clinical trials targeting hepatitis C virus infection. In addition, as cyclophilins are implicated in the predisposition to, or severity of, various diseases, the ability to specifically and effectively modulate their function will prove increasingly useful for disease intervention. In this review, we will summarize the evidence of cyclophilins as key mediators of viral infection and prospective drug targets.",2013 Jul 11,"['Frausto, Stephen D.', 'Lee, Emily', 'Tang, Hengli']",Viruses,,,True
a50f42269649e20ec3580496c72923ef1c4abd6a,PMC,Genomic and Proteomic Analysis of Schizaphis graminum Reveals Cyclophilin Proteins Are Involved in the Transmission of Cereal Yellow Dwarf Virus,http://dx.doi.org/10.1371/journal.pone.0071620,PMC3739738,23951206,CC0,"Yellow dwarf viruses cause the most economically important virus diseases of cereal crops worldwide and are transmitted by aphid vectors. The identification of aphid genes and proteins mediating virus transmission is critical to develop agriculturally sustainable virus management practices and to understand viral strategies for circulative movement in all insect vectors. Two cyclophilin B proteins, S28 and S29, were identified previously in populations of Schizaphisgraminum that differed in their ability to transmit the RPV strain of Cereal yellow dwarf virus (CYDV-RPV). The presence of S29 was correlated with F2 genotypes that were efficient virus transmitters. The present study revealed the two proteins were isoforms, and a single amino acid change distinguished S28 and S29. The distribution of the two alleles was determined in 12 F2 genotypes segregating for CYDV-RPV transmission capacity and in 11 genetically independent, field-collected S . graminum biotypes. Transmission efficiency for CYDV-RPV was determined in all genotypes and biotypes. The S29 isoform was present in all genotypes or biotypes that efficiently transmit CYDV-RPV and more specifically in genotypes that efficiently transport virus across the hindgut. We confirmed a direct interaction between CYDV-RPV and both S28 and S29 using purified virus and bacterially expressed, his-tagged S28 and S29 proteins. Importantly, S29 failed to interact with a closely related virus that is transported across the aphid midgut. We tested for in vivo interactions using an aphid-virus co-immunoprecipitation strategy coupled with a bottom-up LC-MS/MS analysis using a Q Exactive mass spectrometer. This analysis enabled us to identify a third cyclophilin protein, cyclophilin A, interacting directly or in complex with purified CYDV-RPV. Taken together, these data provide evidence that both cyclophilin A and B interact with CYDV-RPV, and these interactions may be important but not sufficient to mediate virus transport from the hindgut lumen into the hemocoel.",2013 Aug 9,"['Tamborindeguy, Cecilia', 'Bereman, Michael S.', 'DeBlasio, Stacy', 'Igwe, David', 'Smith, Dawn M.', 'White, Frank', 'MacCoss, Michael J.', 'Gray, Stewart M.', 'Cilia, Michelle']",PLoS One,,,True
7806d17eeaae9415e597155236a28b9ca9cba137,PMC,Genomic and Proteomic Analysis of Schizaphis graminum Reveals Cyclophilin Proteins Are Involved in the Transmission of Cereal Yellow Dwarf Virus,http://dx.doi.org/10.1371/journal.pone.0071620,PMC3739738,23951206,CC0,"Yellow dwarf viruses cause the most economically important virus diseases of cereal crops worldwide and are transmitted by aphid vectors. The identification of aphid genes and proteins mediating virus transmission is critical to develop agriculturally sustainable virus management practices and to understand viral strategies for circulative movement in all insect vectors. Two cyclophilin B proteins, S28 and S29, were identified previously in populations of Schizaphisgraminum that differed in their ability to transmit the RPV strain of Cereal yellow dwarf virus (CYDV-RPV). The presence of S29 was correlated with F2 genotypes that were efficient virus transmitters. The present study revealed the two proteins were isoforms, and a single amino acid change distinguished S28 and S29. The distribution of the two alleles was determined in 12 F2 genotypes segregating for CYDV-RPV transmission capacity and in 11 genetically independent, field-collected S . graminum biotypes. Transmission efficiency for CYDV-RPV was determined in all genotypes and biotypes. The S29 isoform was present in all genotypes or biotypes that efficiently transmit CYDV-RPV and more specifically in genotypes that efficiently transport virus across the hindgut. We confirmed a direct interaction between CYDV-RPV and both S28 and S29 using purified virus and bacterially expressed, his-tagged S28 and S29 proteins. Importantly, S29 failed to interact with a closely related virus that is transported across the aphid midgut. We tested for in vivo interactions using an aphid-virus co-immunoprecipitation strategy coupled with a bottom-up LC-MS/MS analysis using a Q Exactive mass spectrometer. This analysis enabled us to identify a third cyclophilin protein, cyclophilin A, interacting directly or in complex with purified CYDV-RPV. Taken together, these data provide evidence that both cyclophilin A and B interact with CYDV-RPV, and these interactions may be important but not sufficient to mediate virus transport from the hindgut lumen into the hemocoel.",2013 Aug 9,"['Tamborindeguy, Cecilia', 'Bereman, Michael S.', 'DeBlasio, Stacy', 'Igwe, David', 'Smith, Dawn M.', 'White, Frank', 'MacCoss, Michael J.', 'Gray, Stewart M.', 'Cilia, Michelle']",PLoS One,,,False
b3296f06a1c5c437d06d40c987ef2f13f4b35d59,PMC,Genomic and Proteomic Analysis of Schizaphis graminum Reveals Cyclophilin Proteins Are Involved in the Transmission of Cereal Yellow Dwarf Virus,http://dx.doi.org/10.1371/journal.pone.0071620,PMC3739738,23951206,CC0,"Yellow dwarf viruses cause the most economically important virus diseases of cereal crops worldwide and are transmitted by aphid vectors. The identification of aphid genes and proteins mediating virus transmission is critical to develop agriculturally sustainable virus management practices and to understand viral strategies for circulative movement in all insect vectors. Two cyclophilin B proteins, S28 and S29, were identified previously in populations of Schizaphisgraminum that differed in their ability to transmit the RPV strain of Cereal yellow dwarf virus (CYDV-RPV). The presence of S29 was correlated with F2 genotypes that were efficient virus transmitters. The present study revealed the two proteins were isoforms, and a single amino acid change distinguished S28 and S29. The distribution of the two alleles was determined in 12 F2 genotypes segregating for CYDV-RPV transmission capacity and in 11 genetically independent, field-collected S . graminum biotypes. Transmission efficiency for CYDV-RPV was determined in all genotypes and biotypes. The S29 isoform was present in all genotypes or biotypes that efficiently transmit CYDV-RPV and more specifically in genotypes that efficiently transport virus across the hindgut. We confirmed a direct interaction between CYDV-RPV and both S28 and S29 using purified virus and bacterially expressed, his-tagged S28 and S29 proteins. Importantly, S29 failed to interact with a closely related virus that is transported across the aphid midgut. We tested for in vivo interactions using an aphid-virus co-immunoprecipitation strategy coupled with a bottom-up LC-MS/MS analysis using a Q Exactive mass spectrometer. This analysis enabled us to identify a third cyclophilin protein, cyclophilin A, interacting directly or in complex with purified CYDV-RPV. Taken together, these data provide evidence that both cyclophilin A and B interact with CYDV-RPV, and these interactions may be important but not sufficient to mediate virus transport from the hindgut lumen into the hemocoel.",2013 Aug 9,"['Tamborindeguy, Cecilia', 'Bereman, Michael S.', 'DeBlasio, Stacy', 'Igwe, David', 'Smith, Dawn M.', 'White, Frank', 'MacCoss, Michael J.', 'Gray, Stewart M.', 'Cilia, Michelle']",PLoS One,,,False
adf74045a387615c92918b078dd360d66d64faea,PMC,Genomic and Proteomic Analysis of Schizaphis graminum Reveals Cyclophilin Proteins Are Involved in the Transmission of Cereal Yellow Dwarf Virus,http://dx.doi.org/10.1371/journal.pone.0071620,PMC3739738,23951206,CC0,"Yellow dwarf viruses cause the most economically important virus diseases of cereal crops worldwide and are transmitted by aphid vectors. The identification of aphid genes and proteins mediating virus transmission is critical to develop agriculturally sustainable virus management practices and to understand viral strategies for circulative movement in all insect vectors. Two cyclophilin B proteins, S28 and S29, were identified previously in populations of Schizaphisgraminum that differed in their ability to transmit the RPV strain of Cereal yellow dwarf virus (CYDV-RPV). The presence of S29 was correlated with F2 genotypes that were efficient virus transmitters. The present study revealed the two proteins were isoforms, and a single amino acid change distinguished S28 and S29. The distribution of the two alleles was determined in 12 F2 genotypes segregating for CYDV-RPV transmission capacity and in 11 genetically independent, field-collected S . graminum biotypes. Transmission efficiency for CYDV-RPV was determined in all genotypes and biotypes. The S29 isoform was present in all genotypes or biotypes that efficiently transmit CYDV-RPV and more specifically in genotypes that efficiently transport virus across the hindgut. We confirmed a direct interaction between CYDV-RPV and both S28 and S29 using purified virus and bacterially expressed, his-tagged S28 and S29 proteins. Importantly, S29 failed to interact with a closely related virus that is transported across the aphid midgut. We tested for in vivo interactions using an aphid-virus co-immunoprecipitation strategy coupled with a bottom-up LC-MS/MS analysis using a Q Exactive mass spectrometer. This analysis enabled us to identify a third cyclophilin protein, cyclophilin A, interacting directly or in complex with purified CYDV-RPV. Taken together, these data provide evidence that both cyclophilin A and B interact with CYDV-RPV, and these interactions may be important but not sufficient to mediate virus transport from the hindgut lumen into the hemocoel.",2013 Aug 9,"['Tamborindeguy, Cecilia', 'Bereman, Michael S.', 'DeBlasio, Stacy', 'Igwe, David', 'Smith, Dawn M.', 'White, Frank', 'MacCoss, Michael J.', 'Gray, Stewart M.', 'Cilia, Michelle']",PLoS One,,,False
a77ae8185b435c1d841766ba9d031bab9366b7bd,PMC,Genomic and Proteomic Analysis of Schizaphis graminum Reveals Cyclophilin Proteins Are Involved in the Transmission of Cereal Yellow Dwarf Virus,http://dx.doi.org/10.1371/journal.pone.0071620,PMC3739738,23951206,CC0,"Yellow dwarf viruses cause the most economically important virus diseases of cereal crops worldwide and are transmitted by aphid vectors. The identification of aphid genes and proteins mediating virus transmission is critical to develop agriculturally sustainable virus management practices and to understand viral strategies for circulative movement in all insect vectors. Two cyclophilin B proteins, S28 and S29, were identified previously in populations of Schizaphisgraminum that differed in their ability to transmit the RPV strain of Cereal yellow dwarf virus (CYDV-RPV). The presence of S29 was correlated with F2 genotypes that were efficient virus transmitters. The present study revealed the two proteins were isoforms, and a single amino acid change distinguished S28 and S29. The distribution of the two alleles was determined in 12 F2 genotypes segregating for CYDV-RPV transmission capacity and in 11 genetically independent, field-collected S . graminum biotypes. Transmission efficiency for CYDV-RPV was determined in all genotypes and biotypes. The S29 isoform was present in all genotypes or biotypes that efficiently transmit CYDV-RPV and more specifically in genotypes that efficiently transport virus across the hindgut. We confirmed a direct interaction between CYDV-RPV and both S28 and S29 using purified virus and bacterially expressed, his-tagged S28 and S29 proteins. Importantly, S29 failed to interact with a closely related virus that is transported across the aphid midgut. We tested for in vivo interactions using an aphid-virus co-immunoprecipitation strategy coupled with a bottom-up LC-MS/MS analysis using a Q Exactive mass spectrometer. This analysis enabled us to identify a third cyclophilin protein, cyclophilin A, interacting directly or in complex with purified CYDV-RPV. Taken together, these data provide evidence that both cyclophilin A and B interact with CYDV-RPV, and these interactions may be important but not sufficient to mediate virus transport from the hindgut lumen into the hemocoel.",2013 Aug 9,"['Tamborindeguy, Cecilia', 'Bereman, Michael S.', 'DeBlasio, Stacy', 'Igwe, David', 'Smith, Dawn M.', 'White, Frank', 'MacCoss, Michael J.', 'Gray, Stewart M.', 'Cilia, Michelle']",PLoS One,,,False
896d8340cfc2185b9ba57fa6d3f3b6e93824bac0,PMC,Genomic and Proteomic Analysis of Schizaphis graminum Reveals Cyclophilin Proteins Are Involved in the Transmission of Cereal Yellow Dwarf Virus,http://dx.doi.org/10.1371/journal.pone.0071620,PMC3739738,23951206,CC0,"Yellow dwarf viruses cause the most economically important virus diseases of cereal crops worldwide and are transmitted by aphid vectors. The identification of aphid genes and proteins mediating virus transmission is critical to develop agriculturally sustainable virus management practices and to understand viral strategies for circulative movement in all insect vectors. Two cyclophilin B proteins, S28 and S29, were identified previously in populations of Schizaphisgraminum that differed in their ability to transmit the RPV strain of Cereal yellow dwarf virus (CYDV-RPV). The presence of S29 was correlated with F2 genotypes that were efficient virus transmitters. The present study revealed the two proteins were isoforms, and a single amino acid change distinguished S28 and S29. The distribution of the two alleles was determined in 12 F2 genotypes segregating for CYDV-RPV transmission capacity and in 11 genetically independent, field-collected S . graminum biotypes. Transmission efficiency for CYDV-RPV was determined in all genotypes and biotypes. The S29 isoform was present in all genotypes or biotypes that efficiently transmit CYDV-RPV and more specifically in genotypes that efficiently transport virus across the hindgut. We confirmed a direct interaction between CYDV-RPV and both S28 and S29 using purified virus and bacterially expressed, his-tagged S28 and S29 proteins. Importantly, S29 failed to interact with a closely related virus that is transported across the aphid midgut. We tested for in vivo interactions using an aphid-virus co-immunoprecipitation strategy coupled with a bottom-up LC-MS/MS analysis using a Q Exactive mass spectrometer. This analysis enabled us to identify a third cyclophilin protein, cyclophilin A, interacting directly or in complex with purified CYDV-RPV. Taken together, these data provide evidence that both cyclophilin A and B interact with CYDV-RPV, and these interactions may be important but not sufficient to mediate virus transport from the hindgut lumen into the hemocoel.",2013 Aug 9,"['Tamborindeguy, Cecilia', 'Bereman, Michael S.', 'DeBlasio, Stacy', 'Igwe, David', 'Smith, Dawn M.', 'White, Frank', 'MacCoss, Michael J.', 'Gray, Stewart M.', 'Cilia, Michelle']",PLoS One,,,False
4551a670ee8751ea93b9c5e01ea9ac30fde7ab03,PMC,Economic and Environmental Impacts of Harmful Non-Indigenous Species in Southeast Asia,http://dx.doi.org/10.1371/journal.pone.0071255,PMC3739798,23951120,CC BY,"Harmful non-indigenous species (NIS) impose great economic and environmental impacts globally, but little is known about their impacts in Southeast Asia. Lack of knowledge of the magnitude of the problem hinders the allocation of appropriate resources for NIS prevention and management. We used benefit-cost analysis embedded in a Monte-Carlo simulation model and analysed economic and environmental impacts of NIS in the region to estimate the total burden of NIS in Southeast Asia. The total annual loss caused by NIS to agriculture, human health and the environment in Southeast Asia is estimated to be US$33.5 billion (5(th) and 95(th) percentile US$25.8–39.8 billion). Losses and costs to the agricultural sector are estimated to be nearly 90% of the total (US$23.4–33.9 billion), while the annual costs associated with human health and the environment are US$1.85 billion (US$1.4–2.5 billion) and US$2.1 billion (US$0.9–3.3 billion), respectively, although these estimates are based on conservative assumptions. We demonstrate that the economic and environmental impacts of NIS in low and middle-income regions can be considerable and that further measures, such as the adoption of regional risk assessment protocols to inform decisions on prevention and control of NIS in Southeast Asia, could be beneficial.",2013 Aug 9,"['Nghiem, Le T. P.', 'Soliman, Tarek', 'Yeo, Darren C. J.', 'Tan, Hugh T. W.', 'Evans, Theodore A.', 'Mumford, John D.', 'Keller, Reuben P.', 'Baker, Richard H. A.', 'Corlett, Richard T.', 'Carrasco, Luis R.']",PLoS One,,,True
33ea5a062d23a8c46b7d6e9ba23f1c82f40fde29,PMC,Discovery of a Bovine Enterovirus in Alpaca,http://dx.doi.org/10.1371/journal.pone.0068777,PMC3741315,23950875,CC0,"A cytopathic virus was isolated using Madin-Darby bovine kidney (MDBK) cells from lung tissue of alpaca that died of a severe respiratory infection. To identify the virus, the infected cell culture supernatant was enriched for virus particles and a generic, PCR-based method was used to amplify potential viral sequences. Genomic sequence data of the alpaca isolate was obtained and compared with sequences of known viruses. The new alpaca virus sequence was most similar to recently designated Enterovirus species F, previously bovine enterovirus (BEVs), viruses that are globally prevalent in cattle, although they appear not to cause significant disease. Because bovine enteroviruses have not been previously reported in U.S. alpaca, we suspect that this type of infection is fairly rare, and in this case appeared not to spread beyond the original outbreak. The capsid sequence of the detected virus had greatest homology to Enterovirus F type 1 (indicating that the virus should be considered a member of serotype 1), but the virus had greater homology in 2A protease sequence to type 3, suggesting that it may have been a recombinant. Identifying pathogens that infect a new host species for the first time can be challenging. As the disease in a new host species may be quite different from that in the original or natural host, the pathogen may not be suspected based on the clinical presentation, delaying diagnosis. Although this virus replicated in MDBK cells, existing standard culture and molecular methods could not identify it. In this case, a highly sensitive generic PCR-based pathogen-detection method was used to identify this pathogen.",2013 Aug 12,"['McClenahan, Shasta D.', 'Scherba, Gail', 'Borst, Luke', 'Fredrickson, Richard L.', 'Krause, Philip R.', 'Uhlenhaut, Christine']",PLoS One,,,True
c61f5c4971f07156d3c1d9dd76de4b158855ecc1,PMC,A Protective and Safe Intranasal RSV Vaccine Based on a Recombinant Prefusion-Like Form of the F Protein Bound to Bacterium-Like Particles,http://dx.doi.org/10.1371/journal.pone.0071072,PMC3741363,23951084,CC BY,"Respiratory syncytial virus (RSV) is an important cause of respiratory tract disease in infants and the elderly. Currently, no licensed vaccine against RSV is available. Here we describe the development of a safe and effective intranasal subunit vaccine that is based on recombinant fusion (F) protein bound to the surface of immunostimulatory bacterium-like particles (BLPs) derived from the food-grade bacterium Lactococcus lactis. Different variants of F were analyzed with respect to their conformation and reactivity with neutralizing antibodies, assuming that F proteins mimicking the metastable prefusion form of RSV F expose a more extensive and relevant epitope repertoire than F proteins corresponding to the postfusion structure. Our results indicate that the recombinant soluble ectodomain of RSV F readily adopts a postfusion conformation, generation of which cannot be prevented by C-terminal addition of a trimerization motif, but whose formation is prevented by mutation of the two furin cleavage sites in F. While the putative postfusion form of F is recognized well by the monoclonal antibody Palivizumab, this is much less so for the more potently neutralizing, prefusion-specific antibodies D25 and AM22. Both addition of the trimerization motif and mutation of the furin cleavage sites increased the reactivity of F with D25 and AM22, with the highest reactivity being observed for F proteins in which both these features were combined. Intranasal vaccination of mice or cotton rats with BLPs loaded with this latter prefusion-like F protein (BLP-F), resulted in the potent induction of F-specific immunoglobulins and in significantly decreased virus titers in the lungs upon RSV challenge. Moreover, and in contrast to animals vaccinated with formalin-inactivated RSV, animals that received BLP-F exhibited high levels of F-specific secretory IgA in the nose and RSV-neutralizing antibodies in sera, but did not show symptoms of enhanced disease after challenge with RSV.",2013 Aug 12,"['Rigter, Alan', 'Widjaja, Ivy', 'Versantvoort, Hanneke', 'Coenjaerts, Frank E. J.', 'van Roosmalen, Maarten', 'Leenhouts, Kees', 'Rottier, Peter J. M.', 'Haijema, Bert Jan', 'de Haan, Cornelis A. M.']",PLoS One,,,True
a4e2f812c3232e60ac1af78fed10d292e28906d1,PMC,Using the Electronic Medical Record to Identify Community-Acquired Pneumonia: Toward a Replicable Automated Strategy,http://dx.doi.org/10.1371/journal.pone.0070944,PMC3742728,23967138,CC0,"BACKGROUND: Timely information about disease severity can be central to the detection and management of outbreaks of acute respiratory infections (ARI), including influenza. We asked if two resources: 1) free text, and 2) structured data from an electronic medical record (EMR) could complement each other to identify patients with pneumonia, an ARI severity landmark. METHODS: A manual EMR review of 2747 outpatient ARI visits with associated chest imaging identified x-ray reports that could support the diagnosis of pneumonia (kappa score  = 0.88 (95% CI 0.82∶0.93)), along with attendant cases with Possible Pneumonia (adds either cough, sputum, fever/chills/night sweats, dyspnea or pleuritic chest pain) or with Pneumonia-in-Plan (adds pneumonia stated as a likely diagnosis by the provider). The x-ray reports served as a reference to develop a text classifier using machine-learning software that did not require custom coding. To identify pneumonia cases, the classifier was combined with EMR-based structured data and with text analyses aimed at ARI symptoms in clinical notes. RESULTS: 370 reference cases with Possible Pneumonia and 250 with Pneumonia-in-Plan were identified. The x-ray report text classifier increased the positive predictive value of otherwise identical EMR-based case-detection algorithms by 20–70%, while retaining sensitivities of 58–75%. These performance gains were independent of the case definitions and of whether patients were admitted to the hospital or sent home. Text analyses seeking ARI symptoms in clinical notes did not add further value. CONCLUSION: Specialized software development is not required for automated text analyses to help identify pneumonia patients. These results begin to map an efficient, replicable strategy through which EMR data can be used to stratify ARI severity.",2013 Aug 13,"['DeLisle, Sylvain', 'Kim, Bernard', 'Deepak, Janaki', 'Siddiqui, Tariq', 'Gundlapalli, Adi', 'Samore, Matthew', ""D'Avolio, Leonard""]",PLoS One,,,True
3ae4cc1c1b639a21e95972d63cfe5822b96d136d,PMC,Hazard Analysis of Critical Control Points Assessment as a Tool to Respond to Emerging Infectious Disease Outbreaks,http://dx.doi.org/10.1371/journal.pone.0072279,PMC3743774,23967294,CC BY,"Highly pathogenic avian influenza virus (HPAI) strain H5N1 has had direct and indirect economic impacts arising from direct mortality and control programmes in over 50 countries reporting poultry outbreaks. HPAI H5N1 is now reported as the most widespread and expensive zoonotic disease recorded and continues to pose a global health threat. The aim of this research was to assess the potential of utilising Hazard Analysis of Critical Control Points (HACCP) assessments in providing a framework for a rapid response to emerging infectious disease outbreaks. This novel approach applies a scientific process, widely used in food production systems, to assess risks related to a specific emerging health threat within a known zoonotic disease hotspot. We conducted a HACCP assessment for HPAI viruses within Vietnam’s domestic poultry trade and relate our findings to the existing literature. Our HACCP assessment identified poultry flock isolation, transportation, slaughter, preparation and consumption as critical control points for Vietnam’s domestic poultry trade. Introduction of the preventative measures highlighted through this HACCP evaluation would reduce the risks posed by HPAI viruses and pressure on the national economy. We conclude that this HACCP assessment provides compelling evidence for the future potential that HACCP analyses could play in initiating a rapid response to emerging infectious diseases.",2013 Aug 14,"['Edmunds, Kelly L.', 'Hunter, Paul R.', 'Few, Roger', 'Bell, Diana J.']",PLoS One,,,True
6f779376c8f76658fa6ab19c24748a56ee00aa49,PMC,A Compact Viral Processing Proteinase/Ubiquitin Hydrolase from the OTU Family,http://dx.doi.org/10.1371/journal.ppat.1003560,PMC3744425,23966860,CC BY,"Turnip yellow mosaic virus (TYMV) - a member of the alphavirus-like supergroup of viruses - serves as a model system for positive-stranded RNA virus membrane-bound replication. TYMV encodes a precursor replication polyprotein that is processed by the endoproteolytic activity of its internal cysteine proteinase domain (PRO). We recently reported that PRO is actually a multifunctional enzyme with a specific ubiquitin hydrolase (DUB) activity that contributes to viral infectivity. Here, we report the crystal structure of the 150-residue PRO. Strikingly, PRO displays no homology to other processing proteinases from positive-stranded RNA viruses, including that of alphaviruses. Instead, the closest structural homologs of PRO are DUBs from the Ovarian tumor (OTU) family. In the crystal, one molecule's C-terminus inserts into the catalytic cleft of the next, providing a view of the N-terminal product complex in replication polyprotein processing. This allows us to locate the specificity determinants of PRO for its proteinase substrates. In addition to the catalytic cleft, at the exit of which the active site is unusually pared down and solvent-exposed, a key element in molecular recognition by PRO is a lobe N-terminal to the catalytic domain. Docking models and the activities of PRO and PRO mutants in a deubiquitylating assay suggest that this N-terminal lobe is also likely involved in PRO's DUB function. Our data thus establish that DUBs can evolve to specifically hydrolyze both iso- and endopeptide bonds with different sequences. This is achieved by the use of multiple specificity determinants, as recognition of substrate patches distant from the cleavage sites allows a relaxed specificity of PRO at the sites themselves. Our results thus shed light on how such a compact protein achieves a diversity of key functions in viral genome replication and host-pathogen interaction.",2013 Aug 15,"['Lombardi, Charlotte', 'Ayach, Maya', 'Beaurepaire, Lionel', 'Chenon, Mélanie', 'Andreani, Jessica', 'Guerois, Raphaël', 'Jupin, Isabelle', 'Bressanelli, Stéphane']",PLoS Pathog,,,True
24ea6063ca2c39579eef84d27b3170e6d33a7e27,PMC,A Compact Viral Processing Proteinase/Ubiquitin Hydrolase from the OTU Family,http://dx.doi.org/10.1371/journal.ppat.1003560,PMC3744425,23966860,CC BY,"Turnip yellow mosaic virus (TYMV) - a member of the alphavirus-like supergroup of viruses - serves as a model system for positive-stranded RNA virus membrane-bound replication. TYMV encodes a precursor replication polyprotein that is processed by the endoproteolytic activity of its internal cysteine proteinase domain (PRO). We recently reported that PRO is actually a multifunctional enzyme with a specific ubiquitin hydrolase (DUB) activity that contributes to viral infectivity. Here, we report the crystal structure of the 150-residue PRO. Strikingly, PRO displays no homology to other processing proteinases from positive-stranded RNA viruses, including that of alphaviruses. Instead, the closest structural homologs of PRO are DUBs from the Ovarian tumor (OTU) family. In the crystal, one molecule's C-terminus inserts into the catalytic cleft of the next, providing a view of the N-terminal product complex in replication polyprotein processing. This allows us to locate the specificity determinants of PRO for its proteinase substrates. In addition to the catalytic cleft, at the exit of which the active site is unusually pared down and solvent-exposed, a key element in molecular recognition by PRO is a lobe N-terminal to the catalytic domain. Docking models and the activities of PRO and PRO mutants in a deubiquitylating assay suggest that this N-terminal lobe is also likely involved in PRO's DUB function. Our data thus establish that DUBs can evolve to specifically hydrolyze both iso- and endopeptide bonds with different sequences. This is achieved by the use of multiple specificity determinants, as recognition of substrate patches distant from the cleavage sites allows a relaxed specificity of PRO at the sites themselves. Our results thus shed light on how such a compact protein achieves a diversity of key functions in viral genome replication and host-pathogen interaction.",2013 Aug 15,"['Lombardi, Charlotte', 'Ayach, Maya', 'Beaurepaire, Lionel', 'Chenon, Mélanie', 'Andreani, Jessica', 'Guerois, Raphaël', 'Jupin, Isabelle', 'Bressanelli, Stéphane']",PLoS Pathog,,,True
68422d2849ca1b297e561f73160f9a74a7077797,PMC,Coronaviruses Lacking Exoribonuclease Activity Are Susceptible to Lethal Mutagenesis: Evidence for Proofreading and Potential Therapeutics,http://dx.doi.org/10.1371/journal.ppat.1003565,PMC3744431,23966862,CC BY,"No therapeutics or vaccines currently exist for human coronaviruses (HCoVs). The Severe Acute Respiratory Syndrome-associated coronavirus (SARS-CoV) epidemic in 2002–2003, and the recent emergence of Middle East Respiratory Syndrome coronavirus (MERS-CoV) in April 2012, emphasize the high probability of future zoonotic HCoV emergence causing severe and lethal human disease. Additionally, the resistance of SARS-CoV to ribavirin (RBV) demonstrates the need to define new targets for inhibition of CoV replication. CoVs express a 3′-to-5′ exoribonuclease in nonstructural protein 14 (nsp14-ExoN) that is required for high-fidelity replication and is conserved across the CoV family. All genetic and biochemical data support the hypothesis that nsp14-ExoN has an RNA proofreading function. Thus, we hypothesized that ExoN is responsible for CoV resistance to RNA mutagens. We demonstrate that while wild-type (ExoN+) CoVs were resistant to RBV and 5-fluorouracil (5-FU), CoVs lacking ExoN activity (ExoN−) were up to 300-fold more sensitive. While the primary antiviral activity of RBV against CoVs was not mutagenesis, ExoN− CoVs treated with 5-FU demonstrated both enhanced sensitivity during multi-cycle replication, as well as decreased specific infectivity, consistent with 5-FU functioning as a mutagen. Comparison of full-genome next-generation sequencing of 5-FU treated SARS-CoV populations revealed a 16-fold increase in the number of mutations within the ExoN− population as compared to ExoN+. Ninety percent of these mutations represented A:G and U:C transitions, consistent with 5-FU incorporation during RNA synthesis. Together our results constitute direct evidence that CoV ExoN activity provides a critical proofreading function during virus replication. Furthermore, these studies identify ExoN as the first viral protein distinct from the RdRp that determines the sensitivity of RNA viruses to mutagens. Finally, our results show the importance of ExoN as a target for inhibition, and suggest that small-molecule inhibitors of ExoN activity could be potential pan-CoV therapeutics in combination with RBV or RNA mutagens.",2013 Aug 15,"['Smith, Everett Clinton', 'Blanc, Hervé', 'Vignuzzi, Marco', 'Denison, Mark R.']",PLoS Pathog,,,True
7b0e91e998988ff07f863db25fa8cc0d82ce1183,PMC,A Two-Tube Multiplex Reverse Transcription PCR Assay for Simultaneous Detection of Sixteen Human Respiratory Virus Types/Subtypes,http://dx.doi.org/10.1155/2013/327620,PMC3747601,23984344,CC BY,"There is a need for the development of a rapid and sensitive diagnosis of respiratory viral pathogens. With an intended application in provincial Centers for Diseases Control and Prevention, in this study, we present a two-tube multiplex RT-PCR assay (two-tube assay) using automatic electrophoresis to simultaneously detect sixteen common respiratory viruses. The specificity and the sensitivity of the assay were tested. The assay could detect 20–200 copies per reaction when each viral type was assayed individually, 2000 copies with 9 premixed viral targets in the multiplexed assay in tube 1, and 200 copies with 8 premixed templates in tube 2. A total of 247 specimens were used to evaluate the two-tube assay, and the results were compared with those obtained from the Luminex xTAG RVP Fast assay. The discordant results were confirmed by sequencing or by the Seeplex RV15 ACE detection kit. There were no false positives, but six false negatives occurred with the two-tube assay. In conclusion, the two-tube assay is demonstrated to have great potential for routine surveillance of respiratory virus infection in China.",2013 Aug 5,"['Li, Jin', 'Qi, Shunxiang', 'Zhang, Chen', 'Hu, Xiumei', 'Shen, Hongwei', 'Yang, Mengjie', 'Wang, Ji', 'Wang, Miao', 'Xu, Wenbo', 'Ma, Xuejun']",Biomed Res Int,,,True
790506537d41f8336265c309548c3f95759c7370,PMC,Enhanced Nasal Mucosal Delivery and Immunogenicity of Anti-Caries DNA Vaccine through Incorporation of Anionic Liposomes in Chitosan/DNA Complexes,http://dx.doi.org/10.1371/journal.pone.0071953,PMC3748075,23977186,CC BY,"The design of optimized nanoparticles offers a promising strategy to enable DNA vaccines to cross various physiological barriers for eliciting a specific and protective mucosal immunity via intranasal administration. Here, we reported a new designed nanoparticle system through incorporating anionic liposomes (AL) into chitosan/DNA (CS/DNA) complexes. With enhanced cellular uptake, the constructed AL/CS/DNA nanoparticles can deliver the anti-caries DNA vaccine pGJA-P/VAX into nasal mucosa. TEM results showed the AL/CS/DNA had a spherical structure. High DNA loading ability and effective DNA protection against nuclease were proved by gel electrophoresis. The surface charge of the AL/CS/DNA depended strongly on pH environment, enabling the intracellular release of loaded DNA via a pH-mediated manner. In comparison to the traditional CS/DNA system, our new design rendered a higher transfection efficiency and longer residence time of the AL/CS/DNA at nasal mucosal surface. These outstanding features enable the AL/CS/DNA to induce a significantly (p<0.01) higher level of secretory IgA (SIgA) than the CS/DNA in animal study, and a longer-term mucosal immunity. On the other hand, the AL/CS/DNA exhibited minimal cytotoxicity. These results suggest that the developed nanoparticles offer a potential platform for DNA vaccine packaging and delivery for more efficient elicitation of mucosal immunity.",2013 Aug 20,"['Chen, Liulin', 'Zhu, Junming', 'Li, Yuhong', 'Lu, Jie', 'Gao, Li', 'Xu, Huibi', 'Fan, Mingwen', 'Yang, Xiangliang']",PLoS One,,,True
dcbb50e1f581ab72a3070c7639c8c1a23e031c27,PMC,Metagenomic Analysis of the Ferret Fecal Viral Flora,http://dx.doi.org/10.1371/journal.pone.0071595,PMC3748082,23977082,CC BY,"Ferrets are widely used as a small animal model for a number of viral infections, including influenza A virus and SARS coronavirus. To further analyze the microbiological status of ferrets, their fecal viral flora was studied using a metagenomics approach. Novel viruses from the families Picorna-, Papilloma-, and Anelloviridae as well as known viruses from the families Astro-, Corona-, Parvo-, and Hepeviridae were identified in different ferret cohorts. Ferret kobu- and hepatitis E virus were mainly present in human household ferrets, whereas coronaviruses were found both in household as well as farm ferrets. Our studies illuminate the viral diversity found in ferrets and provide tools to prescreen for newly identified viruses that potentially could influence disease outcome of experimental virus infections in ferrets.",2013 Aug 20,"['Smits, Saskia L.', 'Raj, V. Stalin', 'Oduber, Minoushka D.', 'Schapendonk, Claudia M. E.', 'Bodewes, Rogier', 'Provacia, Lisette', 'Stittelaar, Koert J.', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.']",PLoS One,,,True
5eb34e4b386106962c368bb7c32db8995190e5c6,PMC,Measuring Social Contacts in the Emergency Department,http://dx.doi.org/10.1371/journal.pone.0070854,PMC3749132,23990915,CC BY,"BACKGROUND: Infectious individuals in an emergency department (ED) bring substantial risks of cross infection. Data about the complex social and spatial structure of interpersonal contacts in the ED will aid construction of biologically plausible transmission risk models that can guide cross infection control. METHODS AND FINDINGS: We sought to determine the number and duration of contacts among patients and staff in a large, busy ED. This prospective study was conducted between 1 July 2009 and 30 June 2010. Two 12-hour shifts per week were randomly selected for study. The study was conducted in the ED of an urban hospital. There were 81 shifts in the planned random sample of 104 (78%) with usable contact data, during which there were 9183 patient encounters. Of these, 6062 (66%) were approached to participate, of which 4732 (78%) agreed. Over the course of the year, 88 staff members participated (84%). A radiofrequency identification (RFID) system was installed and the ED divided into 89 distinct zones structured so copresence of two individuals in any zone implied a very high probability of contact <1 meter apart in space. During study observation periods, patients and staff were given RFID tags to wear. Contact events were recorded. These were further broken down with respect to the nature of the contacts, i.e., patient with patient, patient with staff, and staff with staff. 293,171 contact events were recorded, with a median of 22 contact events and 9 contacts with distinct individuals per participant per shift. Staff-staff interactions were more numerous and longer than patient-patient or patient-staff interactions. CONCLUSIONS: We used RFID to quantify contacts between patients and staff in a busy ED. These results are useful for studies of the spread of infections. By understanding contact patterns most important in potential transmission, more effective prevention strategies may be implemented.",2013 Aug 21,"['Lowery-North, Douglas W.', 'Hertzberg, Vicki Stover', 'Elon, Lisa', 'Cotsonis, George', 'Hilton, Sarah A.', 'Vaughns, Christopher F.', 'Hill, Eric', 'Shrestha, Alok', 'Jo, Alexandria', 'Adams, Nathan']",PLoS One,,,True
a013535d6925d423b5d999a4b2e1ded678e190a6,PMC,Causes of Mortality for Indonesian Hajj Pilgrims: Comparison between Routine Death Certificate and Verbal Autopsy Findings,http://dx.doi.org/10.1371/journal.pone.0073243,PMC3749149,23991182,CC BY,"BACKGROUND: Indonesia provides the largest single source of pilgrims for the Hajj (10%). In the last two decades, mortality rates for Indonesian pilgrims ranged between 200–380 deaths per 100,000 pilgrims over the 10-week Hajj period. Reasons for high mortality are not well understood. In 2008, verbal autopsy was introduced to complement routine death certificates to explore cause of death diagnoses. This study presents the patterns and causes of death for Indonesian pilgrims, and compares routine death certificates to verbal autopsy findings. METHODS: Public health surveillance was conducted by Indonesian public health authorities accompanying pilgrims to Saudi Arabia, with daily reporting of hospitalizations and deaths. Surveillance data from 2008 were analyzed for timing, geographic location and site of death. Percentages for each cause of death category from death certificates were compared to that from verbal autopsy. RESULTS: In 2008, 206,831 Indonesian undertook the Hajj. There were 446 deaths, equivalent to 1,968 deaths per 100,000 pilgrim years. Most pilgrims died in Mecca (68%) and Medinah (24%). There was no statistically discernible difference in the total mortality risk for the two pilgrimage routes (Mecca or Medinah first), but the number of deaths peaked earlier for those traveling to Mecca first (p=0.002). Most deaths were due to cardiovascular (66%) and respiratory (28%) diseases. A greater proportion of deaths were attributed to cardiovascular disease by death certificate compared to the verbal autopsy method (p<0.001). Significantly more deaths had ill-defined cause based on verbal autopsy method (p<0.001). CONCLUSIONS: Despite pre-departure health screening and other medical services, Indonesian pilgrim mortality rates were very high. Correct classification of cause of death is critical for the development of risk mitigation strategies. Since verbal autopsy classified causes of death differently to death certificates, further studies are needed to assess the method’s utility in this setting.",2013 Aug 21,"['Pane, Masdalina', 'Imari, Sholah', 'Alwi, Qomariah', 'Nyoman Kandun, I', 'Cook, Alex R.', 'Samaan, Gina']",PLoS One,,,True
300778fc251628966c3c027308a7d3fe5a02f84c,PMC,MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment,http://dx.doi.org/10.1099/vir.0.052910-0,PMC3749523,23620378,CC BY,"Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. The 2003 outbreak of severe acute respiratory syndrome (SARS) highlighted the potentially lethal consequences of CoV-induced disease in humans. In 2012, a novel CoV (Middle East Respiratory Syndrome coronavirus; MERS-CoV) emerged, causing 49 human cases thus far, of which 23 had a fatal outcome. In this study, we characterized MERS-CoV replication and cytotoxicity in human and monkey cell lines. Electron microscopy of infected Vero cells revealed extensive membrane rearrangements, including the formation of double-membrane vesicles and convoluted membranes, which have been implicated previously in the RNA synthesis of SARS-CoV and other CoVs. Following infection, we observed rapidly increasing viral RNA synthesis and release of high titres of infectious progeny, followed by a pronounced cytopathology. These characteristics were used to develop an assay for antiviral compound screening in 96-well format, which was used to identify cyclosporin A as an inhibitor of MERS-CoV replication in cell culture. Furthermore, MERS-CoV was found to be 50–100 times more sensitive to alpha interferon (IFN-α) treatment than SARS-CoV, an observation that may have important implications for the treatment of MERS-CoV-infected patients. MERS-CoV infection did not prevent the IFN-induced nuclear translocation of phosphorylated STAT1, in contrast to infection with SARS-CoV where this block inhibits the expression of antiviral genes. These findings highlight relevant differences between these distantly related zoonotic CoVs in terms of their interaction with and evasion of the cellular innate immune response.",2013 Aug,"['de Wilde, Adriaan H.', 'Raj, V. Stalin', 'Oudshoorn, Diede', 'Bestebroer, Theo M.', 'van Nieuwkoop, Stefan', 'Limpens, Ronald W. A. L.', 'Posthuma, Clara C.', 'van der Meer, Yvonne', 'Bárcena, Montserrat', 'Haagmans, Bart L.', 'Snijder, Eric J.', 'van den Hoogen, Bernadette G.']",J Gen Virol,,,True
4afc459e347836f0f92a75ab0c6cbe2e02e6f3a4,PMC,"Proposals for the classification of human rhinovirus species A, B and C into genotypically assigned types",http://dx.doi.org/10.1099/vir.0.053686-0,PMC3749525,23677786,CC BY,"Human rhinoviruses (HRVs) frequently cause mild upper respiratory tract infections and more severe disease manifestations such as bronchiolitis and asthma exacerbations. HRV is classified into three species within the genus Enterovirus of the family Picornaviridae. HRV species A and B contain 75 and 25 serotypes identified by cross-neutralization assays, although the use of such assays for routine HRV typing is hampered by the large number of serotypes, replacement of virus isolation by molecular methods in HRV diagnosis and the poor or absent replication of HRV species C in cell culture. To address these problems, we propose an alternative, genotypic classification of HRV-based genetic relatedness analogous to that used for enteroviruses. Nucleotide distances between 384 complete VP1 sequences of currently assigned HRV (sero)types identified divergence thresholds of 13, 12 and 13 % for species A, B and C, respectively, that divided inter- and intra-type comparisons. These were paralleled by 10, 9.5 and 10 % thresholds in the larger dataset of >3800 VP4 region sequences. Assignments based on VP1 sequences led to minor revisions of existing type designations (such as the reclassification of serotype pairs, e.g. A8/A95 and A29/A44, as single serotypes) and the designation of new HRV types A101–106, B101–103 and C34–C51. A protocol for assignment and numbering of new HRV types using VP1 sequences and the restriction of VP4 sequence comparisons to type identification and provisional type assignments is proposed. Genotypic assignment and identification of HRV types will be of considerable value in the future investigation of type-associated differences in disease outcomes, transmission and epidemiology.",2013 Aug,"['McIntyre, Chloe L.', 'Knowles, Nick J.', 'Simmonds, Peter']",J Gen Virol,,,True
881abbe78ba9d6d7a690c15464342d1730f327cd,PMC,Identification of MicroRNA-Like RNAs in Mycelial and Yeast Phases of the Thermal Dimorphic Fungus Penicillium marneffei,http://dx.doi.org/10.1371/journal.pntd.0002398,PMC3749987,23991243,CC BY,"BACKGROUND: Penicillium marneffei is the most important thermal dimorphic fungus causing systemic mycosis in China and Southeast Asia. While miRNAs are increasingly recognized for their roles in post-transcriptional regulation of gene expression in animals and plants, miRNAs in fungi were less well studied and their potential roles in fungal dimorphism were largely unknown. Based on P. marneffei genome sequence, we hypothesize that miRNA-like RNAs (milRNAs) may be expressed in the dimorphic fungus. METHODOLOGY/PRINCIPAL FINDINGS: We attempted to identify milRNAs in P. marneffei in both mycelial and yeast phase using high-throughput sequencing technology. Small RNAs were more abundantly expressed in mycelial than yeast phase. Sequence analysis revealed 24 potential milRNA candidates, including 17 candidates in mycelial and seven in yeast phase. Two genes, dcl-1 and dcl-2, encoding putative Dicer-like proteins and the gene, qde-2, encoding Argonaute-like protein, were identified in P. marneffei. Phylogenetic analysis showed that dcl-2 of P. marneffei was more closely related to the homologues in other thermal dimorphic pathogenic fungi than to Penicillium chrysogenum and Aspergillus spp., suggesting the co-evolution of dcl-2 among the thermal dimorphic fungi. Moreover, dcl-2 demonstrated higher mRNA expression levels in mycelial than yeast phase by 7 folds (P<0.001). Northern blot analysis confirmed the expression of two milRNAs, PM-milR-M1 and PM-milR-M2, only in mycelial phase. Using dcl-1(KO), dcl-2(KO), dcl(DKO) and qde-2(KO) deletion mutants, we showed that the biogenesis of both milRNAs were dependent on dcl-2 but not dcl-1 or qde-2. The mRNA expression levels of three predicted targets of PM-milR-M1 were upregulated in knockdown strain PM-milR-M1 (KD), supporting regulatory function of milRNAs. CONCLUSIONS/SIGNIFICANCE: Our findings provided the first evidence for differential expression of milRNAs in different growth phases of thermal dimorphic fungi and shed light on the evolution of fungal proteins involved in milRNA biogenesis and possible role of post-transcriptional control in governing thermal dimorphism.",2013 Aug 22,"['Lau, Susanna K. P.', 'Chow, Wang-Ngai', 'Wong, Annette Y. P.', 'Yeung, Julian M. Y.', 'Bao, Jessie', 'Zhang, Na', 'Lok, Si', 'Woo, Patrick C. Y.', 'Yuen, Kwok-Yung']",PLoS Negl Trop Dis,,,True
682a9c91d32a70c08413f3c3f0daba54239c0af0,PMC,Historical Epidemiology of the Second Cholera Pandemic: Relevance to Present Day Disease Dynamics,http://dx.doi.org/10.1371/journal.pone.0072498,PMC3749991,23991117,CC BY,"Despite nearly two centuries of study, the fundamental transmission dynamic properties of cholera remain incompletely characterized. We used historical time-series data on the spread of cholera in twelve European and North American cities during the second cholera pandemic, as reported in Amariah Brigham’s 1832 A Treatise on Epidemic Cholera, to parameterize simple mathematical models of cholera transmission. Richards growth models were used to derive estimates of the basic reproductive number (R(0)) (median: 16.0, range: 1.9 to 550.9) and the proportion of unrecognized cases (mean: 96.3%, SD: 0.04%). Heterogeneity in model-generated R(0) estimates was consistent with variability in cholera dynamics described by contemporary investigators and may represent differences in the nature of cholera spread. While subject to limitations associated with measurement and the absence of microbiological diagnosis, historical epidemic data are a potentially rich source for understanding pathogen dynamics in the absence of control measures, particularly when used in conjunction with simple and readily interpretable mathematical models.",2013 Aug 22,"['Chan, Christina H.', 'Tuite, Ashleigh R.', 'Fisman, David N.']",PLoS One,,,True
89f70b62cc7e6aa71fbebcc3194b4ea5ad756c99,PMC,Viral Etiology and Clinical Profiles of Children with Severe Acute Respiratory Infections in China,http://dx.doi.org/10.1371/journal.pone.0072606,PMC3750056,23991128,CC BY,"BACKGROUND: No comprehensive analysis is available on the viral etiology and clinical characterization among children with severe acute respiratory infection (SARI) in China during 2009 H1N1 pandemic and post-pandemic period. METHODS: Cohort of 370 hospitalized children (1 to 72 months) with SARI from May 2008 to March 2010 was enrolled in this study. Nasopharyngeal aspirate (NPA) specimens were tested by a commercial assay for 18 respiratory viral targets. The viral distribution and its association with clinical character were statistically analyzed. RESULTS: Viral pathogen was detected in 350 (94.29%) of children with SARI. Overall, the most popular viruses were: enterovirus/rhinovirus (EV/RV) (54.05%), respiratory syncytial virus (RSV) (51.08%), human bocavirus (BoCA) (33.78%), human parainfluenzaviruse type 3 (PIV3) (15.41%), and adenovirus (ADV) (12.97%). Pandemic H1N1 was the dominant influenza virus (IFV) but was only detected in 20 (5.41%) of children. Moreover, detection rate of RSV and human metapneumovirus (hMPV) among suburb participants were significantly higher than that of urban area (P<0.05). Incidence of VSARI among suburb participants was also significant higher, especially among those of 24 to 59 months group (P<0.05). CONCLUSION: Piconaviruses (EV/RV) and paramyxoviruses are the most popular viral pathogens among children with SARI in this study. RSV and hMPV significantly increase the risk of SARI, especially in children younger than 24 months. Higher incidence of VSARI and more susceptibilities to RSV and hMPV infections were found in suburban patients.",2013 Aug 22,"['Zhang, Chen', 'Zhu, Na', 'Xie, Zhengde', 'Lu, Roujian', 'He, Bin', 'Liu, Chunyan', 'Ma, Xuejun', 'Tan, Wenjie']",PLoS One,,,True
ec2b2544b77c203db7fb59fbcb3f2c12733685e1,PMC,The protective effect of recombinant Lactococcus lactis oral vaccine on a Clostridium difficile-infected animal model,http://dx.doi.org/10.1186/1471-230X-13-117,PMC3750240,23865596,CC BY,"BACKGROUND: Oral immunization with vaccines may be an effective strategy for prevention of Clostridium difficile infection (CDI). However, application of previously developed vaccines for preventing CDI has been limited due to various reasons. Here, we developed a recombinant Lactococcus lactis oral vaccine and evaluated its effect on a C. difficile-infected animal model established in golden hamsters in attempt to provide an alternative strategy for CDI prevention. METHODS: Recombinant L. lactis vaccine was developed using the pTRKH2 plasmid, a high-copy-number Escherichia coli-L. shuttle vector: 1) L. lactis expressing secreted proteins was constructed with recombinant pTRKH2 (secreted-protein plasmid) carrying the Usp45 signal peptide (SPUsp45), nontoxic adjuvanted tetanus toxin fragment C (TETC), and 14 of the 38 C-terminal repeats (14CDTA) of nontoxic C. difficile toxin A (TcdA); and 2) L. lactis expressing secreted and membrane proteins was constructed with recombinant pTRKH2 (membrane-anchored plasmid) carrying SPUsp45, TETC, 14CDTA, and the cell wall-anchored sequence of protein M6 (cwaM6). Then, 32 male Syrian golden hamsters were randomly divided into 4 groups (n = 8 each) for gavage of normal saline (blank control) and L. lactis carrying the empty shuttle vector, secreted-protein plasmid, and membrane-anchored plasmid, respectively. After 1-week gavage of clindamycin, the animals were administered with C. difficile spore suspension. General symptoms and intestinal pathological changes of the animals were examined by naked eye and microscopy, respectively. Protein levels of anti-TcdA IgG/IgA antibodies in intestinal tissue and fluid were analyzed by enzyme-linked immunosorbent assay (ELISA). A cell culture cytotoxicity neutralization assay was done by TcdA treatment with or without anti-TcdA serum pre-incubation or treatment. Apoptosis of intestinal epithelial cells was examined by flow cytometry (FL) assay. Expression of mucosal inflammatory cytokines in the animals was detected by polymer chain reaction (PCR) assay. RESULTS: After the C. difficile challenge, the animals of control group had severe diarrhea symptoms on day 1 and all died on day 4, indicating that the CDI animal model was established in hamster. Of the 3 immunization groups, secreted-protein and membrane-anchored plasmid groups had significantly lower mortalities, body weight decreases, and pathological scores, with higher survival rate/time than the empty plasmid group (P < 0.05). The tilter of IgG antibody directed against TcdA was significantly higher in serum and intestinal fluid of secreted-protein and membrane-anchored plasmid groups than in the empty plasmid group (P < 0.05) while the corresponding titer of IgA antibody directed against TcdA had no substantial differences (P > 0.05). The anti-TcdA serum of membrane-anchored plasmid group neutralized the cytotoxicity of 200 ng/ml TcdA with the best protective effect achieved by anti-TcdA serum pre-incubation. The incidences of TcdA-induced death and apoptosis of intestinal epithelial cells were significantly reduced by cell pre-incubation or treatment with anti-TcdA serum of membrane-anchored plasmid group (P < 0.05). MCP-1, ICAM-1, IL-6, and Gro-1 mRNA expression levels were the lowest in cecum tissue of the membrane-anchored groups compared to the other groups. CONCLUSION: Recombinant L. lactis live vaccine is effective for preventing CDI in the hamster model, thus providing an alternative for immunization of C. difficile-associated diseases.",2013 Jul 17,"['Yang, Xiao-qiang', 'Zhao, Ya-gang', 'Chen, Xue-qing', 'Jiang, Bo', 'Sun, Da-yong']",BMC Gastroenterol,,,True
5e80e58924fd2feae8218fc7c2c066e75cec0149,PMC,Level of colorectal cancer awareness: a cross sectional exploratory study among multi-ethnic rural population in Malaysia,http://dx.doi.org/10.1186/1471-2407-13-376,PMC3750380,23924238,CC BY,"BACKGROUND: This paper presents the level of colorectal cancer awareness among multi-ethnic rural population in Malaysia. METHODS: A rural-based cross sectional survey was carried out in Perak state in Peninsular Malaysia in March 2011. The survey recruited a population-representative sample using multistage sampling. Altogether 2379 participants were included in this study. Validated bowel/colorectal cancer awareness measure questionnaire was used to assess the level of colorectal cancer awareness among study population. Analysis of variance (ANOVA) was done to identify socio-demographic variance of knowledge score on warning signs and risk factors of colorectal cancer. RESULTS: Among respondents, 38% and 32% had zero knowledge score for warning signs and risk factors respectively. Mean knowledge score for warning signs and risk factors were 2.89 (SD 2.96) and 3.49 (SD 3.17) respectively. There was a significant positive correlation between the knowledge score of warning signs and level of confidence in detecting a warning sign. Socio-demographic characteristics and having cancer in family and friends play important role in level of awareness. CONCLUSIONS: Level of awareness on colorectal cancer warning signs and risk factors in the rural population of Malaysia is very low. Therefore, it warrants an extensive health education campaign on colorectal cancer awareness as it is one of the commonest cancer in Malaysia. Health education campaign is urgently needed because respondents would seek medical attention sooner if they are aware of this problem.",2013 Aug 7,"['Su, Tin Tin', 'Goh, Jun Yan', 'Tan, Jackson', 'Muhaimah, Abdul Rahim', 'Pigeneswaren, Yoganathan', 'Khairun, Nasirin Sallamun', 'Normazidah, Abdul Wahab', 'Tharisini, Devi Kunasekaran', 'Majid, Hazreen Abd']",BMC Cancer,,,True
ebda8d8ac0eb08bf9bd1c3bc80610f72572d1a73,PMC,Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice,http://dx.doi.org/10.1186/1752-0509-7-69,PMC3750405,23895213,CC BY,"BACKGROUND: Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators – and the relative contributions of each toward viral pathogenicity – is not well-understood. RESULTS: By analyzing a collection of lung samples from mice infected by A/Vietnam/1203/2004 (H5N1; VN1203), we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that inoculation concentrations and four specific mutations in VN1203 mainly impact the magnitude and velocity of the host response kinetics, rather than specific sets of up- and down- regulated genes. We observed analogous kinetic effects using lung samples from mice infected with A/California/04/2009 (H1N1), and we show that these effects correlate with morbidity and viral titer. CONCLUSIONS: We have demonstrated the importance of the kinetics of the host response to H5N1 pathogenesis and its relationship with clinical disease severity and virus replication. These kinetic properties imply that time-matched comparisons of ‘omics profiles to viral infections give limited views to differentiate host-responses. Moreover, these results demonstrate that a fast activation of the host-response at the earliest time points post-infection is critical for protective mechanisms against fast replicating viruses.",2013 Jul 29,"['Tchitchek, Nicolas', 'Eisfeld, Amie J', 'Tisoncik-Go, Jennifer', 'Josset, Laurence', 'Gralinski, Lisa E', 'Bécavin, Christophe', 'Tilton, Susan C', 'Webb-Robertson, Bobbie-Jo', 'Ferris, Martin T', 'Totura, Allison L', 'Li, Chengjun', 'Neumann, Gabriele', 'Metz, Thomas O', 'Smith, Richard D', 'Waters, Katrina M', 'Baric, Ralph', 'Kawaoka, Yoshihiro', 'Katze, Michael G']",BMC Syst Biol,,,True
9ef9504a4ff66e04887a8ea7d2050b8e11e3089e,PMC,Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice,http://dx.doi.org/10.1186/1752-0509-7-69,PMC3750405,23895213,CC BY,"BACKGROUND: Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators – and the relative contributions of each toward viral pathogenicity – is not well-understood. RESULTS: By analyzing a collection of lung samples from mice infected by A/Vietnam/1203/2004 (H5N1; VN1203), we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that inoculation concentrations and four specific mutations in VN1203 mainly impact the magnitude and velocity of the host response kinetics, rather than specific sets of up- and down- regulated genes. We observed analogous kinetic effects using lung samples from mice infected with A/California/04/2009 (H1N1), and we show that these effects correlate with morbidity and viral titer. CONCLUSIONS: We have demonstrated the importance of the kinetics of the host response to H5N1 pathogenesis and its relationship with clinical disease severity and virus replication. These kinetic properties imply that time-matched comparisons of ‘omics profiles to viral infections give limited views to differentiate host-responses. Moreover, these results demonstrate that a fast activation of the host-response at the earliest time points post-infection is critical for protective mechanisms against fast replicating viruses.",2013 Jul 29,"['Tchitchek, Nicolas', 'Eisfeld, Amie J', 'Tisoncik-Go, Jennifer', 'Josset, Laurence', 'Gralinski, Lisa E', 'Bécavin, Christophe', 'Tilton, Susan C', 'Webb-Robertson, Bobbie-Jo', 'Ferris, Martin T', 'Totura, Allison L', 'Li, Chengjun', 'Neumann, Gabriele', 'Metz, Thomas O', 'Smith, Richard D', 'Waters, Katrina M', 'Baric, Ralph', 'Kawaoka, Yoshihiro', 'Katze, Michael G']",BMC Syst Biol,,,False
4e7ebe0cfdc55c3e8cac563b6d787445d7121a01,PMC,Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice,http://dx.doi.org/10.1186/1752-0509-7-69,PMC3750405,23895213,CC BY,"BACKGROUND: Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators – and the relative contributions of each toward viral pathogenicity – is not well-understood. RESULTS: By analyzing a collection of lung samples from mice infected by A/Vietnam/1203/2004 (H5N1; VN1203), we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that inoculation concentrations and four specific mutations in VN1203 mainly impact the magnitude and velocity of the host response kinetics, rather than specific sets of up- and down- regulated genes. We observed analogous kinetic effects using lung samples from mice infected with A/California/04/2009 (H1N1), and we show that these effects correlate with morbidity and viral titer. CONCLUSIONS: We have demonstrated the importance of the kinetics of the host response to H5N1 pathogenesis and its relationship with clinical disease severity and virus replication. These kinetic properties imply that time-matched comparisons of ‘omics profiles to viral infections give limited views to differentiate host-responses. Moreover, these results demonstrate that a fast activation of the host-response at the earliest time points post-infection is critical for protective mechanisms against fast replicating viruses.",2013 Jul 29,"['Tchitchek, Nicolas', 'Eisfeld, Amie J', 'Tisoncik-Go, Jennifer', 'Josset, Laurence', 'Gralinski, Lisa E', 'Bécavin, Christophe', 'Tilton, Susan C', 'Webb-Robertson, Bobbie-Jo', 'Ferris, Martin T', 'Totura, Allison L', 'Li, Chengjun', 'Neumann, Gabriele', 'Metz, Thomas O', 'Smith, Richard D', 'Waters, Katrina M', 'Baric, Ralph', 'Kawaoka, Yoshihiro', 'Katze, Michael G']",BMC Syst Biol,,,False
8670e7c9c70220663ce166e38e0adba8c6d7de18,PMC,Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice,http://dx.doi.org/10.1186/1752-0509-7-69,PMC3750405,23895213,CC BY,"BACKGROUND: Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators – and the relative contributions of each toward viral pathogenicity – is not well-understood. RESULTS: By analyzing a collection of lung samples from mice infected by A/Vietnam/1203/2004 (H5N1; VN1203), we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that inoculation concentrations and four specific mutations in VN1203 mainly impact the magnitude and velocity of the host response kinetics, rather than specific sets of up- and down- regulated genes. We observed analogous kinetic effects using lung samples from mice infected with A/California/04/2009 (H1N1), and we show that these effects correlate with morbidity and viral titer. CONCLUSIONS: We have demonstrated the importance of the kinetics of the host response to H5N1 pathogenesis and its relationship with clinical disease severity and virus replication. These kinetic properties imply that time-matched comparisons of ‘omics profiles to viral infections give limited views to differentiate host-responses. Moreover, these results demonstrate that a fast activation of the host-response at the earliest time points post-infection is critical for protective mechanisms against fast replicating viruses.",2013 Jul 29,"['Tchitchek, Nicolas', 'Eisfeld, Amie J', 'Tisoncik-Go, Jennifer', 'Josset, Laurence', 'Gralinski, Lisa E', 'Bécavin, Christophe', 'Tilton, Susan C', 'Webb-Robertson, Bobbie-Jo', 'Ferris, Martin T', 'Totura, Allison L', 'Li, Chengjun', 'Neumann, Gabriele', 'Metz, Thomas O', 'Smith, Richard D', 'Waters, Katrina M', 'Baric, Ralph', 'Kawaoka, Yoshihiro', 'Katze, Michael G']",BMC Syst Biol,,,False
235a2dcaae4126e0c1afeb28607fc683d4a6bfbb,PMC,Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice,http://dx.doi.org/10.1186/1752-0509-7-69,PMC3750405,23895213,CC BY,"BACKGROUND: Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators – and the relative contributions of each toward viral pathogenicity – is not well-understood. RESULTS: By analyzing a collection of lung samples from mice infected by A/Vietnam/1203/2004 (H5N1; VN1203), we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that inoculation concentrations and four specific mutations in VN1203 mainly impact the magnitude and velocity of the host response kinetics, rather than specific sets of up- and down- regulated genes. We observed analogous kinetic effects using lung samples from mice infected with A/California/04/2009 (H1N1), and we show that these effects correlate with morbidity and viral titer. CONCLUSIONS: We have demonstrated the importance of the kinetics of the host response to H5N1 pathogenesis and its relationship with clinical disease severity and virus replication. These kinetic properties imply that time-matched comparisons of ‘omics profiles to viral infections give limited views to differentiate host-responses. Moreover, these results demonstrate that a fast activation of the host-response at the earliest time points post-infection is critical for protective mechanisms against fast replicating viruses.",2013 Jul 29,"['Tchitchek, Nicolas', 'Eisfeld, Amie J', 'Tisoncik-Go, Jennifer', 'Josset, Laurence', 'Gralinski, Lisa E', 'Bécavin, Christophe', 'Tilton, Susan C', 'Webb-Robertson, Bobbie-Jo', 'Ferris, Martin T', 'Totura, Allison L', 'Li, Chengjun', 'Neumann, Gabriele', 'Metz, Thomas O', 'Smith, Richard D', 'Waters, Katrina M', 'Baric, Ralph', 'Kawaoka, Yoshihiro', 'Katze, Michael G']",BMC Syst Biol,,,False
a666fb5ccc487de7063bca9a179137052c0eeff1,PMC,Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice,http://dx.doi.org/10.1186/1752-0509-7-69,PMC3750405,23895213,CC BY,"BACKGROUND: Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators – and the relative contributions of each toward viral pathogenicity – is not well-understood. RESULTS: By analyzing a collection of lung samples from mice infected by A/Vietnam/1203/2004 (H5N1; VN1203), we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that inoculation concentrations and four specific mutations in VN1203 mainly impact the magnitude and velocity of the host response kinetics, rather than specific sets of up- and down- regulated genes. We observed analogous kinetic effects using lung samples from mice infected with A/California/04/2009 (H1N1), and we show that these effects correlate with morbidity and viral titer. CONCLUSIONS: We have demonstrated the importance of the kinetics of the host response to H5N1 pathogenesis and its relationship with clinical disease severity and virus replication. These kinetic properties imply that time-matched comparisons of ‘omics profiles to viral infections give limited views to differentiate host-responses. Moreover, these results demonstrate that a fast activation of the host-response at the earliest time points post-infection is critical for protective mechanisms against fast replicating viruses.",2013 Jul 29,"['Tchitchek, Nicolas', 'Eisfeld, Amie J', 'Tisoncik-Go, Jennifer', 'Josset, Laurence', 'Gralinski, Lisa E', 'Bécavin, Christophe', 'Tilton, Susan C', 'Webb-Robertson, Bobbie-Jo', 'Ferris, Martin T', 'Totura, Allison L', 'Li, Chengjun', 'Neumann, Gabriele', 'Metz, Thomas O', 'Smith, Richard D', 'Waters, Katrina M', 'Baric, Ralph', 'Kawaoka, Yoshihiro', 'Katze, Michael G']",BMC Syst Biol,,,False
aab412e1a2fee75cf3e3fbc911d985ac004f866e,PMC,Probiotic Lactobacillus rhamnosus GG mono-association suppresses human rotavirus-induced autophagy in the gnotobiotic piglet intestine,http://dx.doi.org/10.1186/1757-4749-5-22,PMC3750464,23924832,CC BY,"BACKGROUND: Human rotavirus (HRV) is the most important cause of severe diarrhea in infants and young children. Probiotic Lactobacillus rhamnosus GG (LGG) reduces rotavirus infection and diarrhea. However, the molecular mechanisms of LGG-mediated protection from rotavirus infection are poorly understood. Autophagy plays an essential role in responses to microbial pathogens. However, the role of autophagy in HRV infection and LGG treatment is unknown. We hypothesize that rotavirus gastroenteritis activates autophagy and that LGG suppresses virus-induced autophagy and prevents intestinal damage in infected piglets. METHODS: We used LGG feeding to combat viral gastroenteritis in the gnotobiotic pig model of virulent HRV infection. RESULTS: We found that LGG feeding did not increase autophagy, whereas virus infection induced autophagy in the piglet intestine. Virus infection increased the protein levels of the autophagy markers ATG16L1 and Beclin-1 and the autophagy regulator mTOR. LGG treatment during viral gastroenteritis reduced autophagy marker expression to normal levels, induced apoptosis and partially prevented virus-induced tissue damage. CONCLUSION: Our study provides new insights into virus-induced autophagy and LGG suppression of uncontrolled autophagy and intestinal injury. A better understanding of the antiviral activity of LGG will lead to novel therapeutic strategies for infant infectious diseases.",2013 Aug 7,"['Wu, Shaoping', 'Yuan, Lijuan', 'Zhang, Yongguo', 'Liu, Fangning', 'Li, Guohua', 'Wen, Ke', 'Kocher, Jacob', 'Yang, Xingdong', 'Sun, Jun']",Gut Pathog,,,True
6d20ab75d7394461e9acd16899bd55902177d8fe,PMC,Initiation of human astrovirus type 1 infection was blocked by inhibitors of phosphoinositide 3-kinase,http://dx.doi.org/10.1186/1743-422X-10-153,PMC3750554,23680019,CC BY,"BACKGROUND: Upon initial contact with a virus, host cells activate a series of cellular signaling cascades that facilitate viral entry and viral propagation within the cell. Little is known about how the human astrovirus (HAstV) exploits signaling cascades to establish an infection in host cells. Recent studies showed that activation of extracellular signal-regulated kinase 1/2 (ERK1/2) is important for HAstV infection, though the involvement of other signaling cascades remains unclear. METHODS: A panel of kinase blockers was used to search for cellular signaling pathways important for HAstV1 infection. To determine their impact on the infectious process, we examined viral gene expression, RNA replication, and viral RNA and capsid protein release from host cells. RESULTS: Inhibitors of phosphoinositide 3-kinase (PI3K) activation interfered with the infection, independent of their effect on ERK 1/2 activation. Activation of the PI3K signaling cascade occurred at an early phase of the infection, judging from the timeframe of Akt phosphorylation. PI3K inhibition at early times, but not at later times, blocked viral gene expression. However, inhibiting the downstream targets of PI3K activation, Akt and Rac1, did not block infection. Inhibition of protein kinase A (PKA) activation was found to block a later phase of HAstV1 production. CONCLUSIONS: Our results reveal a previously unknown, essential role of PI3K in the life cycle of HAstV1. PI3K participates in the early stage of infection, possibly during the viral entry process. Our results also reveal the role of PKA in viral production.",2013 May 16,"['Tange, Shoichiro', 'Zhou, Yan', 'Nagakui-Noguchi, Yuko', 'Imai, Takeshi', 'Nakanishi, Akira']",Virol J,,,True
cf66e218ffa8ed3d638c5ddff568753609aac808,PMC,Changing trends and serotype distribution of Shigella species in Beijing from 1994 to 2010,http://dx.doi.org/10.1186/1757-4749-5-21,PMC3750644,23919811,CC BY,"Shigella species are a common cause of acute diarrheal disease in China. In this study, we characterized the changing trends and serotype distribution of Shigella species in Beijing from 1994 to 2010. A total of 5999 Shigella strains were isolated and serotyped from the 302nd Hospital in Beijing. The annual number of Shigella isolates reached a peak (n = 1192; 19.84%) in 1996 and then decreased annually, reaching the lowest point (n = 24; 0.41%) in 2010. S. flexneri 2a and S. sonnei were the most frequently isolated Shigella, with their respective isolates making up 53.3% and 27.6% of the total. Isolates of S. flexneri 4c, 4a, and x made up 3% respectively of the total isolates. Significant decreases in percentage of S. flexneri over time were observed. S. sonnei surpassed S. flexneri 2a as the predominant serotype in 2000. Most isolates were recovered from July to September; 13.6% of the isolates were recovered from children aged 0 to 5 years, and 16% were recovered from those aged 21 to 25 years. S. flexneri 2a and 5 were recovered mostly from males (33.41%, p < 0.001; and 0.46%, p < 0.001%; respectively), whereas S. flexneri 2b and 6, and S. sonnei were most often isolated from females. Continuous monitoring of Shigella showed that all 4 species and 27 serotypes were present in Beijing, China, during the study period. The emergence of S. sonnei and the overall decreasing isolation rate of Shigella in Beijing can potentially aid in the development of vaccine and control strategies for shigellosis in the city.",2013 Aug 7,"['Mao, Yuanli', 'Cui, Enbo', 'Bao, Chunmei', 'Liu, Zhenhong', 'Chen, Suming', 'Zhang, Juling', 'Wang, Huan', 'Zhang, Chenglong', 'Zou, Jing', 'Klena, John D', 'Zhu, Baoli', 'Qu, Fen', 'Wang, Zhiyun']",Gut Pathog,,,True
7c0bfcf7cdb720113a16c54e8203111137ebbd41,PMC,Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry,http://dx.doi.org/10.1186/1471-2180-13-187,PMC3750913,23924316,CC BY,"BACKGROUND: We previously identified two hydrolyzable tannins, chebulagic acid (CHLA) and punicalagin (PUG) that blocked herpes simplex virus type 1 (HSV-1) entry and spread. These compounds inhibited viral glycoprotein interactions with cell surface glycosaminoglycans (GAGs). Based on this property, we evaluated their antiviral efficacy against several different viruses known to employ GAGs for host cell entry. RESULTS: Extensive analysis of the tannins’ mechanism of action was performed on a panel of viruses during the attachment and entry steps of infection. Virus-specific binding assays and the analysis of viral spread during treatment with these compounds were also conducted. CHLA and PUG were effective in abrogating infection by human cytomegalovirus (HCMV), hepatitis C virus (HCV), dengue virus (DENV), measles virus (MV), and respiratory syncytial virus (RSV), at μM concentrations and in dose-dependent manners without significant cytotoxicity. Moreover, the natural compounds inhibited viral attachment, penetration, and spread, to different degrees for each virus. Specifically, the tannins blocked all these steps of infection for HCMV, HCV, and MV, but had little effect on the post-fusion spread of DENV and RSV, which could suggest intriguing differences in the roles of GAG-interactions for these viruses. CONCLUSIONS: CHLA and PUG may be of value as broad-spectrum antivirals for limiting emerging/recurring viruses known to engage host cell GAGs for entry. Further studies testing the efficacy of these tannins in vivo against certain viruses are justified.",2013 Aug 7,"['Lin, Liang-Tzung', 'Chen, Ting-Ying', 'Lin, Song-Chow', 'Chung, Chueh-Yao', 'Lin, Ta-Chen', 'Wang, Guey-Horng', 'Anderson, Robert', 'Lin, Chun-Ching', 'Richardson, Christopher D']",BMC Microbiol,,,True
40886c8a1c173dab7ef1685c544a7554f63bd6ff,PMC,Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease,http://dx.doi.org/10.1186/1741-7015-11-181,PMC3750926,23945277,CC BY,"Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients. Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype. This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes. These patients are therefore a priority for research and treatment. The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection. Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment. Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype. This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.",2013 Aug 14,"['Wedzicha, Jadwiga A', 'Brill, Simon E', 'Allinson, James P', 'Donaldson, Gavin C']",BMC Med,,,True
a09a978336b5c98928dbfb37b12da84d327bfe2d,PMC,Viral protein R of human immunodeficiency virus type-1 induces retrotransposition of long interspersed element-1,http://dx.doi.org/10.1186/1742-4690-10-83,PMC3751050,23915234,CC BY,"BACKGROUND: Viral protein R (Vpr), a protein of human immunodeficiency virus type-1 (HIV-1) with various biological functions, was shown to be present in the blood of HIV-1-positive patients. However, it remained unclear whether circulating Vpr in patients’ blood is biologically active. Here, we examined the activity of blood Vpr using an assay system by which retrotransposition of long interspersed element-1 (L1-RTP) was detected. We also investigated the in vivo effects of recombinant Vpr (rVpr) by administrating it to transgenic mice harboring human L1 as a transgene (hL1-Tg mice). Based on our data, we discuss the involvement of blood Vpr in the clinical symptoms of acquired immunodeficiency syndrome (AIDS). RESULTS: We first discovered that rVpr was active in induction of L1-RTP. Biochemical analyses revealed that rVpr-induced L1-RTP depended on the aryl hydrocarbon receptor, mitogen-activated protein kinases, and CCAAT/enhancer-binding protein β. By using a sensitive L1-RTP assay system, we showed that 6 of the 15 blood samples from HIV-1 patients examined were positive for induction of L1-RTP. Of note, the L1-RTP-inducing activity was blocked by a monoclonal antibody specific for Vpr. Moreover, L1-RTP was reproducibly induced in various organs, including the kidney, when rVpr was administered to hL1-Tg mice. CONCLUSIONS: Blood Vpr is biologically active, suggesting that its monitoring is worthwhile for clarification of the roles of Vpr in the pathogenesis of AIDS. This is the first report to demonstrate a soluble factor in patients’ blood active for L1-RTP activity, and implies the involvement of L1-RTP in the development of human diseases.",2013 Aug 5,"['Iijima, Kenta', 'Okudaira, Noriyuki', 'Tamura, Masato', 'Doi, Akihiro', 'Saito, Yoshikazu', 'Shimura, Mari', 'Goto, Motohito', 'Matsunaga, Akihiro', 'Kawamura, Yuki I', 'Otsubo, Takeshi', 'Dohi, Taeko', 'Hoshino, Shigeki', 'Kano, Shigeyuki', 'Hagiwara, Shotaro', 'Tanuma, Junko', 'Gatanaga, Hiroyuki', 'Baba, Masanori', 'Iguchi, Taku', 'Yanagita, Motoko', 'Oka, Shinichi', 'Okamura, Tadashi', 'Ishizaka, Yukihito']",Retrovirology,,,True
35105bb6ba037441c3366e7ea8d59dbcb9245c1b,PMC,Frequency of D222G haemagglutinin mutant of pandemic (H1N1) pdm09 influenza virus in Tunisia between 2009 and 2011,http://dx.doi.org/10.1186/1746-1596-8-124,PMC3751102,23902660,CC BY,"BACKGROUND: The novel pandemic A (H1N1) pdm09 virus was first identified in Mexico in April 2009 and since then it spread worldwide over a short period of time. Although the virus infection is generally associated with mild disease and a relatively low mortality, it is projected that mutations in specific regions of the viral genome, especially within the receptor binding domain of the haemagglutinin (HA) protein could result in more virulent virus stains, leading to a more severe pathogenicity. METHODS: To monitor the genetic polymorphisms at position 222 of Haemagglutinin of influenza A(H1N1)pdm09 viruses from both outpatients with mild influenza and individuals with severe disease requiring hospitalization, during 2009–2010 and 2010–2011 seasons, a sequence-based genotypic assessment of viral populations to understand the prevalence of D222G mutation. RESULTS: The D222G was identified in clinical specimens from 3 out of 42 cases analyzed in Tunisia with severe outcome (7%). Interestingly, in one fatal case out of four viruses taken from fatal cases studied (25%). Also this mutation was found in one mild case out of 8 mild cases studied (0.1%). D222E substitution was found in virus taken from one patient with severe clinical syndrome (2%) out of 42 severe cases analyzed and E374K substitution was found in two severe cases (4%) out of 42 severe cases studied. CONCLUSIONS: A specific mutation in the viral haemagglutinin (D222G) was found in fatal, severe and mild case. Further virological, clinical and epidemiological investigations are needed to ascertain the role of this and other mutations that may alter the virulence and transmissibility of the pandemic influenza A (H1N1)pdm09. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1027334947811255",2013 Jul 31,"['Moussi, Awatef El', 'Kacem, Mohamed Ali Ben Hadj', 'Pozo, Francisco', 'Ledesma, Juan', 'Cuevas, Maria Teresa', 'Casas, Inmaculada', 'Slim, Amine']",Diagn Pathol,,,True
b0022167496e4388b198ab691103ffe066e0c9cc,PMC,Complete Genome Sequence Analysis of a Reassortant Strain of Bluetongue Virus Serotype 16 from Italy,http://dx.doi.org/10.1128/genomeA.00622-13,PMC3751604,23969049,CC BY,"The complete genome sequence of a reassortant field strain of bluetongue virus serotype 16 (BTV-16), isolated from cattle in the Apulia region of Italy in 2002, has been determined by Illumina sequencing. Sequence comparisons of segment 1 (Seg-1) to Seg-10, except Seg-5, show that BTV-16 strain ITL2002 belongs to the major eastern topotype of BTV.",2013 Aug 22,"['Lorusso, Alessio', 'Costessi, Adalberto', 'Pirovano, Walter', 'Marcacci, Maurilia', 'Cammà, Cesare', 'Savini, Giovanni']",Genome Announc,,,True
bab3d2a212eaf7740a45ee8efeec3db99bf94589,PMC,"Complete Genome Sequence of a Very Virulent Porcine Epidemic Diarrhea Virus Strain, CH/GDGZ/2012, Isolated in Southern China",http://dx.doi.org/10.1128/genomeA.00645-13,PMC3751607,23969052,CC BY,"The classical symptoms of porcine epidemic diarrhea (PED) are acute diarrhea and dehydration. The isolated porcine epidemic diarrhea virus (PEDV) CH/GDGZ/2012 strain was obtained from the feces of diseased pigs in 2012 in southern China. We report the complete genome sequence of strain CH/GDGZ/2012, which might be useful for better understanding the molecular characteristics of this virus.",2013 Aug 22,"['Tian, Ye', 'Su, Danping', 'Zhang, Haiming', 'Chen, Rui-ai', 'He, Dongsheng']",Genome Announc,,,True
ffe7169e14eea9af001ae388632123d43eeb9697,PMC,Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection,http://dx.doi.org/10.1186/1471-2172-14-40,PMC3751766,23947615,CC BY,"BACKGROUND: Some studies have shown that nasally administered immunobiotics had the potential to improve the outcome of influenza virus infection. However, the capacity of immunobiotics to improve protection against respiratory syncytial virus (RSV) infection was not investigated before. OBJECTIVE: The aims of this study were: a) to evaluate whether the nasal administration of Lactobacillus rhamnosus CRL1505 (Lr05) and L. rhamnosus CRL1506 (Lr06) are able to improve respiratory antiviral defenses and beneficially modulate the immune response triggered by TLR3/RIG-I activation; b) to investigate whether viability of Lr05 or Lr06 is indispensable to modulate respiratory immunity and; c) to evaluate the capacity of Lr05 and Lr06 to improve the resistance of infant mice against RSV infection. RESULTS: Nasally administered Lr05 and Lr06 differentially modulated the TLR3/RIG-I-triggered antiviral respiratory immune response. Lr06 administration significantly modulated the production of IFN-α, IFN-β and IL-6 in the response to poly(I:C) challenge, while nasal priming with Lr05 was more effective to improve levels of IFN-γ and IL-10. Both viable Lr05 and Lr06 strains increased the resistance of infant mice to RSV infection while only heat-killed Lr05 showed a protective effect similar to those observed with viable strains. CONCLUSIONS: The present work demonstrated that nasal administration of immunobiotics is able to beneficially modulate the immune response triggered by TLR3/RIG-I activation in the respiratory tract and to increase the resistance of mice to the challenge with RSV. Comparative studies using two Lactobacillus rhamnosus strains of the same origin and with similar technological properties showed that each strain has an specific immunoregulatory effect in the respiratory tract and that they differentially modulate the immune response after poly(I:C) or RSV challenges, conferring different degree of protection and using distinct immune mechanisms. We also demonstrated in this work that it is possible to beneficially modulate the respiratory defenses against RSV by using heat-killed immunobiotics.",2013 Aug 15,"['Tomosada, Yohsuke', 'Chiba, Eriko', 'Zelaya, Hortensia', 'Takahashi, Takuya', 'Tsukida, Kohichiro', 'Kitazawa, Haruki', 'Alvarez, Susana', 'Villena, Julio']",BMC Immunol,,,True
76b1bad1aba249a858d1112096bbc4fbf3ae7d5d,PMC,Inhibition of hepatitis B virus (HBV) gene expression and replication by HBx gene silencing in a hydrodynamic injection mouse model with a new clone of HBV genotype B,http://dx.doi.org/10.1186/1743-422X-10-214,PMC3751867,23805945,CC BY,"BACKGROUND: It has been suggested that different hepatitis B virus (HBV) genotypes may have distinct virological characteristics that correlate with clinical outcomes during antiviral therapy and the natural course of infection. Hydrodynamic injection (HI) of HBV in the mouse model is a useful tool for study of HBV replication in vivo. However, only HBV genotype A has been used for studies with HI. METHODS: We constructed 3 replication-competent clones containing 1.1, 1.2 and 1.3 fold overlength of a HBV genotype B genome and tested them both in vitro and in vivo. Moreover, A HBV genotype B clone based on the pAAV-MCS vector was constructed with the 1.3 fold HBV genome, resulting in the plasmid pAAV-HBV1.3(B) and tested by HI in C57BL/6 mice. Application of siRNA against HBx gene was tested in HBV genotype B HI mouse model. RESULTS: The 1.3 fold HBV clone showed higher replication and gene expression than the 1.1 and 1.2 fold HBV clones. Compared with pAAV-HBV1.2 (genotype A), the mice HI with pAAV-HBV1.3(B) showed higher HBsAg and HBeAg expression as well as HBV DNA replication level but a higher clearance rate. Application of two plasmids pSB-HBxi285 and pSR-HBxi285 expressing a small/short interfering RNA (siRNA) to the HBx gene in HBV genotype B HI mouse model, leading to an inhibition of HBV gene expression and replication. However, HBV gene expression may resume in some mice despite an initial delay, suggesting that transient suppression of HBV replication by siRNA may be insufficient to prevent viral spread, particularly if the gene silencing is not highly effective. CONCLUSIONS: Taken together, the HI mouse model with a HBV genotype B genome was successfully established and showed different characteristics in vivo compared with the genotype A genome. The effectiveness of gene silencing against HBx gene determines whether HBV replication may be sustainably inhibited by siRNA in vivo.",2013 Jun 28,"['Li, Lei', 'Shen, Hong', 'Li, Anyi', 'Zhang, Zhenhua', 'Wang, Baoju', 'Wang, Junzhong', 'Zheng, Xin', 'Wu, Jun', 'Yang, Dongliang', 'Lu, Mengji', 'Song, Jingjiao']",Virol J,,,True
0d6a162406af842f2324077d73de17b2e85cffdb,PMC,Comparative Evaluation of Six Commercialized Multiplex PCR Kits for the Diagnosis of Respiratory Infections,http://dx.doi.org/10.1371/journal.pone.0072174,PMC3751960,24058410,CC BY,"The molecular diagnosis of respiratory infection can be performed using different commercial multiplex-based PCR kits whose performances have been previously compared individually to those of conventional techniques. This study compared the practicability and the diagnostic performances of six CE-marked kits available in 2011 on the French market, including 2 detecting viruses and atypical bacteria (from Pathofinder and Seegene companies) and 4 detecting only viruses (from Abbott, Genomica, Qiagen and Seegene companies). The respective sensitivity, specificity, accuracy and agreement of each multiplex technique were calculated by comparison to commercial duplex PCR tests (Argene/bioMérieux) used as gold standard. Eighty-eight respiratory specimens with no pathogen (n = 11), single infections (n = 33) or co-infections (n = 44) were selected to cover 9 viruses or groups of viruses and 3 atypical bacteria. All samples were extracted using the NUCLISENS® easyMAG™ instrument (bioMérieux). The overall sensitivity ranged from 56.25% to 91.67% for viruses and was below 50% with both tests for bacteria. The overall specificity was excellent (>94% for all pathogens). For each tested kit, the overall agreement with the reference test was strong for viruses (kappa test >0.60) and moderate for bacteria. After the extraction step, the hands-on time varied from 50 min to 2h30 and the complete results were available in 2h30 to 9 h. The spectrum of tested agents and the technology used to reveal the PCR products as well as the laboratory organization are determinant for the selection of a kit.",2013 Aug 23,"['Pillet, Sylvie', 'Lardeux, Marina', 'Dina, Julia', 'Grattard, Florence', 'Verhoeven, Paul', 'Le Goff, Jérôme', 'Vabret, Astrid', 'Pozzetto, Bruno']",PLoS One,,,True
9ce462cb0807906c475d4b600afac950c7e8c4e8,PMC,Get the News Out Loudly and Quickly: The Influence of the Media on Limiting Emerging Infectious Disease Outbreaks,http://dx.doi.org/10.1371/journal.pone.0071692,PMC3753329,23990974,CC BY,"During outbreaks of infectious diseases with high morbidity and mortality, individuals closely follow media reports of the outbreak. Many will attempt to minimize contacts with other individuals in order to protect themselves from infection and possibly death. This process is called social distancing. Social distancing strategies include restricting socializing and travel, and using barrier protections. We use modeling to show that for short-term outbreaks, social distancing can have a large influence on reducing outbreak morbidity and mortality. In particular, public health agencies working together with the media can significantly reduce the severity of an outbreak by providing timely accounts of new infections and deaths. Our models show that the most effective strategy to reduce infections is to provide this information as early as possible, though providing it well into the course of the outbreak can still have a significant effect. However, our models for long-term outbreaks indicate that reporting historic infection data can result in more infections than with no reporting at all. We examine three types of media influence and we illustrate the media influence with a simulated outbreak of a generic emerging infectious disease in a small city. Social distancing can never be complete; however, for a spectrum of outbreaks, we show that leaving isolation (stopping applying social distancing measures) for up to 4 hours each day has modest effect on the overall morbidity and mortality.",2013 Aug 26,"['Mummert, Anna', 'Weiss, Howard']",PLoS One,,,True
462a0562fd2597131766176ce8f001ada8728a91,PMC,Get the News Out Loudly and Quickly: The Influence of the Media on Limiting Emerging Infectious Disease Outbreaks,http://dx.doi.org/10.1371/journal.pone.0071692,PMC3753329,23990974,CC BY,"During outbreaks of infectious diseases with high morbidity and mortality, individuals closely follow media reports of the outbreak. Many will attempt to minimize contacts with other individuals in order to protect themselves from infection and possibly death. This process is called social distancing. Social distancing strategies include restricting socializing and travel, and using barrier protections. We use modeling to show that for short-term outbreaks, social distancing can have a large influence on reducing outbreak morbidity and mortality. In particular, public health agencies working together with the media can significantly reduce the severity of an outbreak by providing timely accounts of new infections and deaths. Our models show that the most effective strategy to reduce infections is to provide this information as early as possible, though providing it well into the course of the outbreak can still have a significant effect. However, our models for long-term outbreaks indicate that reporting historic infection data can result in more infections than with no reporting at all. We examine three types of media influence and we illustrate the media influence with a simulated outbreak of a generic emerging infectious disease in a small city. Social distancing can never be complete; however, for a spectrum of outbreaks, we show that leaving isolation (stopping applying social distancing measures) for up to 4 hours each day has modest effect on the overall morbidity and mortality.",2013 Aug 26,"['Mummert, Anna', 'Weiss, Howard']",PLoS One,,,False
b55409d93e144178d64a7a39b46e4b160f8d03a5,PMC,Get the News Out Loudly and Quickly: The Influence of the Media on Limiting Emerging Infectious Disease Outbreaks,http://dx.doi.org/10.1371/journal.pone.0071692,PMC3753329,23990974,CC BY,"During outbreaks of infectious diseases with high morbidity and mortality, individuals closely follow media reports of the outbreak. Many will attempt to minimize contacts with other individuals in order to protect themselves from infection and possibly death. This process is called social distancing. Social distancing strategies include restricting socializing and travel, and using barrier protections. We use modeling to show that for short-term outbreaks, social distancing can have a large influence on reducing outbreak morbidity and mortality. In particular, public health agencies working together with the media can significantly reduce the severity of an outbreak by providing timely accounts of new infections and deaths. Our models show that the most effective strategy to reduce infections is to provide this information as early as possible, though providing it well into the course of the outbreak can still have a significant effect. However, our models for long-term outbreaks indicate that reporting historic infection data can result in more infections than with no reporting at all. We examine three types of media influence and we illustrate the media influence with a simulated outbreak of a generic emerging infectious disease in a small city. Social distancing can never be complete; however, for a spectrum of outbreaks, we show that leaving isolation (stopping applying social distancing measures) for up to 4 hours each day has modest effect on the overall morbidity and mortality.",2013 Aug 26,"['Mummert, Anna', 'Weiss, Howard']",PLoS One,,,False
55d1bc868ea9e1d565c85b250aa7195b95c80f43,PMC,Get the News Out Loudly and Quickly: The Influence of the Media on Limiting Emerging Infectious Disease Outbreaks,http://dx.doi.org/10.1371/journal.pone.0071692,PMC3753329,23990974,CC BY,"During outbreaks of infectious diseases with high morbidity and mortality, individuals closely follow media reports of the outbreak. Many will attempt to minimize contacts with other individuals in order to protect themselves from infection and possibly death. This process is called social distancing. Social distancing strategies include restricting socializing and travel, and using barrier protections. We use modeling to show that for short-term outbreaks, social distancing can have a large influence on reducing outbreak morbidity and mortality. In particular, public health agencies working together with the media can significantly reduce the severity of an outbreak by providing timely accounts of new infections and deaths. Our models show that the most effective strategy to reduce infections is to provide this information as early as possible, though providing it well into the course of the outbreak can still have a significant effect. However, our models for long-term outbreaks indicate that reporting historic infection data can result in more infections than with no reporting at all. We examine three types of media influence and we illustrate the media influence with a simulated outbreak of a generic emerging infectious disease in a small city. Social distancing can never be complete; however, for a spectrum of outbreaks, we show that leaving isolation (stopping applying social distancing measures) for up to 4 hours each day has modest effect on the overall morbidity and mortality.",2013 Aug 26,"['Mummert, Anna', 'Weiss, Howard']",PLoS One,,,False
95ee3b41047edd02d74ab869375f1dcb7b83c31c,PMC,Co-expression of RNA–protein complexes in Escherichia coli and applications to RNA biology,http://dx.doi.org/10.1093/nar/gkt576,PMC3753655,23804766,CC BY,"RNA has emerged as a major player in many cellular processes. Understanding these processes at the molecular level requires homogeneous RNA samples for structural, biochemical and pharmacological studies. We previously devised a generic approach that allows efficient in vivo expression of recombinant RNA in Escherichia coli. In this work, we have extended this method to RNA/protein co-expression. We have engineered several plasmids that allow overexpression of RNA–protein complexes in E. coli. We have investigated the potential of these tools in many applications, including the production of nuclease-sensitive RNAs encapsulated in viral protein pseudo-particles, the co-production of non-coding RNAs with chaperone proteins, the incorporation of a post-transcriptional RNA modification by co-production with the appropriate modifying enzyme and finally the production and purification of an RNA–His-tagged protein complex by nickel affinity chromatography. We show that this last application easily provides pure material for crystallographic studies. The new tools we report will pave the way to large-scale structural and molecular investigations of RNA function and interactions with proteins.",2013 Aug 25,"['Ponchon, Luc', 'Catala, Marjorie', 'Seijo, Bili', 'El Khouri, Marguerite', 'Dardel, Frédéric', 'Nonin-Lecomte, Sylvie', 'Tisné, Carine']",Nucleic Acids Res,,,True
d604b2fa9328520de1cb77b550803b82b6bbbe87,PMC,Duplex Molecular Assay Intended for Point-of-Care Diagnosis of Influenza A/B Virus Infection,http://dx.doi.org/10.1128/JCM.00740-13,PMC3754654,23850955,CC BY,"Early diagnosis and management of influenza virus infection directly correlates with the effectiveness in disease control. Current molecular influenza virus tests were designed for use in diagnostic testing facilities, where sophisticated equipment and highly trained technicians are available. A longer turnaround time for the centralized testing than when testing near the sample source could delay the initiation of medical intervention, thereby reducing the efficacy of antiviral treatment. The new assay, the SAMBA (simple amplification-based assay) Flu duplex test, is a dipstick-based molecular assay developed to provide a simple, accurate, and cost-effective solution for the diagnosis of influenza A/B viruses intended for near-patient testing. The test presents an alternative format of influenza virus molecular testing that utilizes isothermal amplification and visual detection of nucleic acid on a test strip. The entire test procedure (extraction, amplification, and detection) is integrated into an enclosed semiautomated system. Analytically, the SAMBA Flu duplex test detects 95 and 85 copies of viral genomes for influenza A and B viruses, respectively, with no cross-reactivity observed against other common respiratory pathogens. The clinical performance was established by blind testing of 328 nasal/throat and nasopharyngeal swab specimens from the United Kingdom and Belgium and comparing the results with the quantitative reverse transcription-PCR method routinely used in two public health laboratories. The SAMBA Flu duplex test showed a clinical sensitivity and specificity of 100% and 97.9% for influenza virus A and 100% and 100% for influenza virus B. The test provides a new technology that could facilitate simple and timely identification of influenza virus infection, potentially resulting in more efficient control measures.",2013 Sep,"['Wu, Liang-Ta', 'Thomas, Isabelle', 'Curran, Martin D.', 'Ellis, Joanna S.', 'Parmar, Surendra', 'Goel, Neha', 'Sharma, Pia I.', 'Allain, Jean-Pierre', 'Lee, Helen H.']",J Clin Microbiol,,,True
06c172a11ee30931ac537dfb70ce020dced50918,PMC,"The Mongoose, the Pheasant, the Pox, and the Retrovirus",http://dx.doi.org/10.1371/journal.pbio.1001641,PMC3754884,24013523,CC BY,"Paleovirology is the study of ancient viruses. The existence of a paleovirus can sometimes be detected by virtue of its accidental insertion into the germline of different animal species, which allows one to date when the virus actually existed. However, the ancient and the modern often connect, as modern viruses have unexpected origins that can be traced to ancient infections. The genomes of two species of mongooses and an egg-laying mammal called an echidna show that a virus currently present in poultry, the reticuloendotheliosis virus (REV), is actually of ancient exotic mammalian origin. REV apparently spread to poultry through a circuitous route involving the isolation of malaria parasites from a pheasant from Borneo housed at the Bronx Zoo that was contaminated with REV. Repeated passage of this virus in poultry adapted the virus to its new host. At some point, the virus got inserted into another virus, called fowlpox virus, which has spread back into the wild. Although REV may still exist somewhere in a mammalian host, its modern form links an 8 million-year-old infection of the ancestor of a mongoose to a virus that now is circulating in wild birds through malaria studies in the mid-20(th) century. These lessons of ancient and modern viruses have implications for modern human pandemics from viral reservoirs and for human interventions that may come with unintended consequences.",2013 Aug 27,"['Etienne, Lucie', 'Emerman, Michael']",PLoS Biol,,,True
db7b6440cfdfd2bbf71c22361d4ea606a16d4643,PMC,iGPCR-Drug: A Web Server for Predicting Interaction between GPCRs and Drugs in Cellular Networking,http://dx.doi.org/10.1371/journal.pone.0072234,PMC3754978,24015221,CC BY,"Involved in many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs) are among the most frequent targets of therapeutic drugs. It is time-consuming and expensive to determine whether a drug and a GPCR are to interact with each other in a cellular network purely by means of experimental techniques. Although some computational methods were developed in this regard based on the knowledge of the 3D (dimensional) structure of protein, unfortunately their usage is quite limited because the 3D structures for most GPCRs are still unknown. To overcome the situation, a sequence-based classifier, called “iGPCR-drug”, was developed to predict the interactions between GPCRs and drugs in cellular networking. In the predictor, the drug compound is formulated by a 2D (dimensional) fingerprint via a 256D vector, GPCR by the PseAAC (pseudo amino acid composition) generated with the grey model theory, and the prediction engine is operated by the fuzzy K-nearest neighbour algorithm. Moreover, a user-friendly web-server for iGPCR-drug was established at http://www.jci-bioinfo.cn/iGPCR-Drug/. For the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated math equations presented in this paper just for its integrity. The overall success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is remarkably higher than the rate by the existing peer method developed in 2010 although no web server was ever established for it. It is anticipated that iGPCR-Drug may become a useful high throughput tool for both basic research and drug development, and that the approach presented here can also be extended to study other drug – target interaction networks.",2013 Aug 27,"['Xiao, Xuan', 'Min, Jian-Liang', 'Wang, Pu', 'Chou, Kuo-Chen']",PLoS One,,,True
b47bbf9315d63e713950bc5b5c15f9299411cc9f,PMC,iGPCR-Drug: A Web Server for Predicting Interaction between GPCRs and Drugs in Cellular Networking,http://dx.doi.org/10.1371/journal.pone.0072234,PMC3754978,24015221,CC BY,"Involved in many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs) are among the most frequent targets of therapeutic drugs. It is time-consuming and expensive to determine whether a drug and a GPCR are to interact with each other in a cellular network purely by means of experimental techniques. Although some computational methods were developed in this regard based on the knowledge of the 3D (dimensional) structure of protein, unfortunately their usage is quite limited because the 3D structures for most GPCRs are still unknown. To overcome the situation, a sequence-based classifier, called “iGPCR-drug”, was developed to predict the interactions between GPCRs and drugs in cellular networking. In the predictor, the drug compound is formulated by a 2D (dimensional) fingerprint via a 256D vector, GPCR by the PseAAC (pseudo amino acid composition) generated with the grey model theory, and the prediction engine is operated by the fuzzy K-nearest neighbour algorithm. Moreover, a user-friendly web-server for iGPCR-drug was established at http://www.jci-bioinfo.cn/iGPCR-Drug/. For the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated math equations presented in this paper just for its integrity. The overall success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is remarkably higher than the rate by the existing peer method developed in 2010 although no web server was ever established for it. It is anticipated that iGPCR-Drug may become a useful high throughput tool for both basic research and drug development, and that the approach presented here can also be extended to study other drug – target interaction networks.",2013 Aug 27,"['Xiao, Xuan', 'Min, Jian-Liang', 'Wang, Pu', 'Chou, Kuo-Chen']",PLoS One,,,False
cb9ca284ea7badccc5e93a2c3f5eb2f34598aecb,PMC,iGPCR-Drug: A Web Server for Predicting Interaction between GPCRs and Drugs in Cellular Networking,http://dx.doi.org/10.1371/journal.pone.0072234,PMC3754978,24015221,CC BY,"Involved in many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs) are among the most frequent targets of therapeutic drugs. It is time-consuming and expensive to determine whether a drug and a GPCR are to interact with each other in a cellular network purely by means of experimental techniques. Although some computational methods were developed in this regard based on the knowledge of the 3D (dimensional) structure of protein, unfortunately their usage is quite limited because the 3D structures for most GPCRs are still unknown. To overcome the situation, a sequence-based classifier, called “iGPCR-drug”, was developed to predict the interactions between GPCRs and drugs in cellular networking. In the predictor, the drug compound is formulated by a 2D (dimensional) fingerprint via a 256D vector, GPCR by the PseAAC (pseudo amino acid composition) generated with the grey model theory, and the prediction engine is operated by the fuzzy K-nearest neighbour algorithm. Moreover, a user-friendly web-server for iGPCR-drug was established at http://www.jci-bioinfo.cn/iGPCR-Drug/. For the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated math equations presented in this paper just for its integrity. The overall success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is remarkably higher than the rate by the existing peer method developed in 2010 although no web server was ever established for it. It is anticipated that iGPCR-Drug may become a useful high throughput tool for both basic research and drug development, and that the approach presented here can also be extended to study other drug – target interaction networks.",2013 Aug 27,"['Xiao, Xuan', 'Min, Jian-Liang', 'Wang, Pu', 'Chou, Kuo-Chen']",PLoS One,,,False
de88e6c770596c1e10e37b72c6303490d03ede05,PMC,iGPCR-Drug: A Web Server for Predicting Interaction between GPCRs and Drugs in Cellular Networking,http://dx.doi.org/10.1371/journal.pone.0072234,PMC3754978,24015221,CC BY,"Involved in many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs) are among the most frequent targets of therapeutic drugs. It is time-consuming and expensive to determine whether a drug and a GPCR are to interact with each other in a cellular network purely by means of experimental techniques. Although some computational methods were developed in this regard based on the knowledge of the 3D (dimensional) structure of protein, unfortunately their usage is quite limited because the 3D structures for most GPCRs are still unknown. To overcome the situation, a sequence-based classifier, called “iGPCR-drug”, was developed to predict the interactions between GPCRs and drugs in cellular networking. In the predictor, the drug compound is formulated by a 2D (dimensional) fingerprint via a 256D vector, GPCR by the PseAAC (pseudo amino acid composition) generated with the grey model theory, and the prediction engine is operated by the fuzzy K-nearest neighbour algorithm. Moreover, a user-friendly web-server for iGPCR-drug was established at http://www.jci-bioinfo.cn/iGPCR-Drug/. For the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated math equations presented in this paper just for its integrity. The overall success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is remarkably higher than the rate by the existing peer method developed in 2010 although no web server was ever established for it. It is anticipated that iGPCR-Drug may become a useful high throughput tool for both basic research and drug development, and that the approach presented here can also be extended to study other drug – target interaction networks.",2013 Aug 27,"['Xiao, Xuan', 'Min, Jian-Liang', 'Wang, Pu', 'Chou, Kuo-Chen']",PLoS One,,,False
6f251e71a441068ffe96970bf5d857713ec30163,PMC,Modulation of Protease Activated Receptor 1 Influences Human Metapneumovirus Disease Severity in a Mouse Model,http://dx.doi.org/10.1371/journal.pone.0072529,PMC3755973,24015257,CC BY,"Human metapneumovirus (hMPV) infection causes acute respiratory tract infections (RTI) which can result in hospitalization of both children and adults. To date, no antiviral or vaccine is available for this common viral infection. Immunomodulators could represent an interesting strategy for the treatment of severe viral infection. Recently, the role of protease-activated receptors (PAR) in inflammation, coagulation and infection processes has been of growing interest. Herein, the effects of a PAR1 agonist and a PAR1 antagonist on hMPV infection were investigated in BALB/c mice. Intranasal administration of the PAR1 agonist resulted in increased weight loss and mortality of infected mice. Conversely, the PAR1 antagonist was beneficial to hMPV infection by decreasing weight loss and clinical signs and by significantly reducing pulmonary inflammation, pro-inflammatory cytokine levels (including IL-6, KC and MCP-1) and recruitment of immune cells to the lungs. In addition, a significant reduction in pulmonary viral titers was also observed in the lungs of PAR1 antagonist-treated mice. Despite no apparent direct effect on virus replication during in vitro experiments, an important role for PAR1 in the regulation of furin expression in the lungs was shown for the first time. Further experiments indicated that the hMPV fusion protein can be cleaved by furin thus suggesting that PAR1 could have an effect on viral infectivity in addition to its immunomodulatory properties. Thus, inhibition of PAR1 by selected antagonists could represent an interesting strategy for decreasing the severity of paramyxovirus infections.",2013 Aug 28,"['Aerts, Laetitia', 'Hamelin, Marie-Ève', 'Rhéaume, Chantal', 'Lavigne, Sophie', 'Couture, Christian', 'Kim, WooJin', 'Susan-Resiga, Delia', 'Prat, Annik', 'Seidah, Nabil G.', 'Vergnolle, Nathalie', 'Riteau, Beatrice', 'Boivin, Guy']",PLoS One,,,True
5b029e946adb1adaf73c953ca02413da64fc6c53,PMC,Use of a Small Peptide Fragment as an Inhibitor of Insulin Fibrillation Process: A Study by High and Low Resolution Spectroscopy,http://dx.doi.org/10.1371/journal.pone.0072318,PMC3756998,24009675,CC BY,"A non-toxic, nine residue peptide, NIVNVSLVK is shown to interfere with insulin fibrillation by various biophysical methods. Insulin undergoes conformational changes under certain stress conditions leading to amyloid fibrils. Fibrillation of insulin poses a problem in its long-term storage, reducing its efficacy in treating type II diabetes. The dissociation of insulin oligomer to monomer is the key step for the onset of fibrillation. The time course of insulin fibrillation at 62°C using Thioflavin T fluorescence shows an increase in the lag time from 120 min without peptide to 236 min with peptide. Transmission electron micrographs show branched insulin fibrils in its absence and less inter-fibril association in its presence. Upon incubation at 62°C and pH 2.6, insulin lost some α-helical structure as seen by Fourier transformed infra-red spectroscopy (FT-IR), but if the peptide is added, secondary structure is almost fully maintained for 3 h, though lost partially at 4 h. FT-IR spectroscopy also shows that insulin forms the cross beta structure indicative of fibrils beyond 2 h, but in the presence of the peptide, α-helix retention is seen till 4 h. Both size exclusion chromatography and dynamic light scattering show that insulin primarily exists as trimer, whose conversion to a monomer is resisted by the peptide. Saturation transfer difference nuclear magnetic resonance confirms that the hydrophobic residues in the peptide are in close contact with an insulin hydrophobic groove. Molecular dynamics simulations in conjunction with principal component analyses reveal how the peptide interrupts insulin fibrillation. In vitro hemolytic activity of the peptide showed insignificant cytotoxicity against HT1080 cells. The insulin aggregation is probed due to the inter play of two key residues, Phe(B24) and Tyr(B26) monitored from molecular dynamics simulations studies. Further new peptide based leads may be developed from this nine residue peptide.",2013 Aug 29,"['Banerjee, Victor', 'Kar, Rajiv K.', 'Datta, Aritreyee', 'Parthasarathi, Krupakar', 'Chatterjee, Subhrangsu', 'Das, Kali P.', 'Bhunia, Anirban']",PLoS One,,,True
63f776d8ae5084cc5a3aa5e09aa55f1a302b1b1f,PMC,Identification and Survey of a Novel Avian Coronavirus in Ducks,http://dx.doi.org/10.1371/journal.pone.0072918,PMC3758261,24023656,CC BY,"The rapid discovery of novel viruses using next generation sequencing (NGS) technologies including DNA-Seq and RNA-Seq, has greatly expanded our understanding of viral diversity in recent years. The timely identification of novel viruses using NGS technologies is also important for us to control emerging infectious diseases caused by novel viruses. In this study, we identified a novel duck coronavirus (CoV), distinct with chicken infectious bronchitis virus (IBV), using RNA-Seq. The novel duck-specific CoV was a potential novel species within the genus Gammacoronavirus, as indicated by sequences of three regions in the viral 1b gene. We also performed a survey of CoVs in domestic fowls in China using reverse-transcription polymerase chain reaction (RT-PCR), targeting the viral nucleocapsid (N) gene. A total of 102 CoV positives were identified through the survey. Phylogenetic analysis of the viral N sequences suggested that CoVs in domestic fowls have diverged into several region-specific or host-specific clades or subclades in the world, and IBVs can infect ducks, geese and pigeons, although they mainly circulate in chickens. Moreover, this study provided novel data supporting the notion that some host-specific CoVs other than IBVs circulate in ducks, geese and pigeons, and indicated that the novel duck-specific CoV identified through RNA-Seq in this study is genetically closer to some CoVs circulating in wild water fowls. Taken together, this study shed new insight into the diversity, distribution, evolution and control of avian CoVs.",2013 Aug 30,"['Chen, Gui-Qian', 'Zhuang, Qing-Ye', 'Wang, Kai-Cheng', 'Liu, Shuo', 'Shao, Jian-Zhong', 'Jiang, Wen-Ming', 'Hou, Guang-Yu', 'Li, Jin-Ping', 'Yu, Jian-Min', 'Li, Yi-Ping', 'Chen, Ji-Ming']",PLoS One,,,True
b2fde3b77f54db50b124bca17aaba10069e4424b,PMC,Estimating a Markovian Epidemic Model Using Household Serial Interval Data from the Early Phase of an Epidemic,http://dx.doi.org/10.1371/journal.pone.0073420,PMC3758268,24023679,CC BY,"The clinical serial interval of an infectious disease is the time between date of symptom onset in an index case and the date of symptom onset in one of its secondary cases. It is a quantity which is commonly collected during a pandemic and is of fundamental importance to public health policy and mathematical modelling. In this paper we present a novel method for calculating the serial interval distribution for a Markovian model of household transmission dynamics. This allows the use of Bayesian MCMC methods, with explicit evaluation of the likelihood, to fit to serial interval data and infer parameters of the underlying model. We use simulated and real data to verify the accuracy of our methodology and illustrate the importance of accounting for household size. The output of our approach can be used to produce posterior distributions of population level epidemic characteristics.",2013 Aug 30,"['Black, Andrew J.', 'Ross, Joshua V.']",PLoS One,,,True
33e9e969d555d597b3af0d6c4bdb38010ce3996d,PMC,Estimating a Markovian Epidemic Model Using Household Serial Interval Data from the Early Phase of an Epidemic,http://dx.doi.org/10.1371/journal.pone.0073420,PMC3758268,24023679,CC BY,"The clinical serial interval of an infectious disease is the time between date of symptom onset in an index case and the date of symptom onset in one of its secondary cases. It is a quantity which is commonly collected during a pandemic and is of fundamental importance to public health policy and mathematical modelling. In this paper we present a novel method for calculating the serial interval distribution for a Markovian model of household transmission dynamics. This allows the use of Bayesian MCMC methods, with explicit evaluation of the likelihood, to fit to serial interval data and infer parameters of the underlying model. We use simulated and real data to verify the accuracy of our methodology and illustrate the importance of accounting for household size. The output of our approach can be used to produce posterior distributions of population level epidemic characteristics.",2013 Aug 30,"['Black, Andrew J.', 'Ross, Joshua V.']",PLoS One,,,True
4903f4b49cff9b009f9413ae245ecb75bd97960c,PMC,"Differential Sensitivity of Bat Cells to Infection by Enveloped RNA Viruses: Coronaviruses, Paramyxoviruses, Filoviruses, and Influenza Viruses",http://dx.doi.org/10.1371/journal.pone.0072942,PMC3758312,24023659,CC BY,"Bats (Chiroptera) host major human pathogenic viruses including corona-, paramyxo, rhabdo- and filoviruses. We analyzed six different cell lines from either Yinpterochiroptera (including African flying foxes and a rhinolophid bat) or Yangochiroptera (genera Carollia and Tadarida) for susceptibility to infection by different enveloped RNA viruses. None of the cells were sensitive to infection by transmissible gastroenteritis virus (TGEV), a porcine coronavirus, or to infection mediated by the Spike (S) protein of SARS-coronavirus (SARS-CoV) incorporated into pseudotypes based on vesicular stomatitis virus (VSV). The resistance to infection was overcome if cells were transfected to express the respective cellular receptor, porcine aminopeptidase N for TGEV or angiotensin-converting enzyme 2 for SARS-CoV. VSV pseudotypes containing the S proteins of two bat SARS-related CoV (Bg08 and Rp3) were unable to infect any of the six tested bat cell lines. By contrast, viral pseudotypes containing the surface protein GP of Marburg virus from the family Filoviridae infected all six cell lines though at different efficiency. Notably, all cells were sensitive to infection by two paramyxoviruses (Sendai virus and bovine respiratory syncytial virus) and three influenza viruses from different subtypes. These results indicate that bat cells are more resistant to infection by coronaviruses than to infection by paramyxoviruses, filoviruses and influenza viruses. Furthermore, these results show a receptor-dependent restriction of the infection of bat cells by CoV. The implications for the isolation of coronaviruses from bats are discussed.",2013 Aug 30,"['Hoffmann, Markus', 'Müller, Marcel Alexander', 'Drexler, Jan Felix', 'Glende, Jörg', 'Erdt, Meike', 'Gützkow, Tim', 'Losemann, Christoph', 'Binger, Tabea', 'Deng, Hongkui', 'Schwegmann-Weßels, Christel', 'Esser, Karl-Heinz', 'Drosten, Christian', 'Herrler, Georg']",PLoS One,,,True
a71052d0d97adb979510b675275149d05cd7976e,PMC,Assessment of the Evolution of Cancer Treatment Therapies,http://dx.doi.org/10.3390/cancers3033279,PMC3759197,24212956,CC BY,"Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.). In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine). We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.",2011 Aug 12,"['Arruebo, Manuel', 'Vilaboa, Nuria', 'Sáez-Gutierrez, Berta', 'Lambea, Julio', 'Tres, Alejandro', 'Valladares, Mónica', 'González-Fernández, África']",Cancers (Basel),,,True
443aa07a6f57cab4c25fcdb0add50527028d6769,PMC,Emerging Cancer Vaccines: The Promise of Genetic Vectors,http://dx.doi.org/10.3390/cancers3033687,PMC3759217,24212974,CC BY,"Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost.",2011 Sep 22,"['Aurisicchio, Luigi', 'Ciliberto, Gennaro']",Cancers (Basel),,,True
946087e7d17c7256e8c90187ee7d27f3df870919,PMC,Asymmetry of Cell Division in CFSE-Based Lymphocyte Proliferation Analysis,http://dx.doi.org/10.3389/fimmu.2013.00264,PMC3759284,24032033,CC BY,"Flow cytometry-based analysis of lymphocyte division using carboxyfluorescein succinimidyl ester (CFSE) dye dilution permits acquisition of data describing cellular proliferation and differentiation. For example, CFSE histogram data enable quantitative insight into cellular turnover rates by applying mathematical models and parameter estimation techniques. Several mathematical models have been developed using different types of deterministic or stochastic approaches. However, analysis of CFSE proliferation assays is based on the premise that the label is halved in the two daughter cells. Importantly, asymmetry of protein distribution in lymphocyte division is a basic biological feature of cell division with the degree of the asymmetry depending on various factors. Here, we review the recent literature on asymmetric lymphocyte division and CFSE-based lymphocyte proliferation analysis. We suggest that division- and label-structured mathematical models describing CFSE-based cell proliferation should take into account asymmetry and time-lag in cell proliferation. Utilization of improved modeling algorithms will permit straightforward quantification of essential parameters describing the performance of activated lymphocytes.",2013 Sep 2,"['Bocharov, Gennady', 'Luzyanina, Tatyana', 'Cupovic, Jovana', 'Ludewig, Burkhard']",Front Immunol,,,True
e24a0cd976fbe3f6a625425e6c9899d52af1067f,PMC,Sialic Acid Binding Properties of Soluble Coronavirus Spike (S1) Proteins: Differences between Infectious Bronchitis Virus and Transmissible Gastroenteritis Virus,http://dx.doi.org/10.3390/v5081924,PMC3761233,23896748,CC BY,"The spike proteins of a number of coronaviruses are able to bind to sialic acids present on the cell surface. The importance of this sialic acid binding ability during infection is, however, quite different. We compared the spike protein of transmissible gastroenteritis virus (TGEV) and the spike protein of infectious bronchitis virus (IBV). Whereas sialic acid is the only receptor determinant known so far for IBV, TGEV requires interaction with its receptor aminopeptidase N to initiate infection of cells. Binding tests with soluble spike proteins carrying an IgG Fc-tag revealed pronounced differences between these two viral proteins. Binding of the IBV spike protein to host cells was in all experiments sialic acid dependent, whereas the soluble TGEV spike showed binding to APN but had no detectable sialic acid binding activity. Our results underline the different ways in which binding to sialoglycoconjugates is mediated by coronavirus spike proteins.",2013 Jul 26,"['Shahwan, Katarina', 'Hesse, Martina', 'Mork, Ann-Kathrin', 'Herrler, Georg', 'Winter, Christine']",Viruses,,,True
d92d26c41ab17c1cf0bea776233045118ffecb84,PMC,"Molecular Characterization and Phylogenetic Analysis of New Variants of the Porcine Epidemic Diarrhea Virus in Gansu, China in 2012",http://dx.doi.org/10.3390/v5081991,PMC3761238,23955500,CC BY,"Between January 2012 and March 2012, the infection rates of porcine epidemic diarrhea virus (PEDV) increased substantially in vaccinated swine herds in many porcine farms in Gansu Province, China. The spike (S) glycoprotein is an important determinant for PEDV biological properties. To determine the distribution profile of PEDV outbreak strains, we sequenced the full-length S gene of five samples from two farms where animals exhibited severe diarrhea and high mortality rates. Five new PEDV variants were identified, and the molecular diversity, phylogenetic relationships, and antigenicity analysis of Gansu field samples with other PEDV reference strains were investigated. A series of insertions, deletions, and mutations in the S gene was found in five PEDV variants compared with classical and vaccine strains. These mutations may provide stronger pathogenicity and antigenicity to the new PEDV variants that influenced the effectiveness of the CV777-based vaccine. Our results suggest that these new PEDV variant strains in Gansu Province might be from South Korean or South China, and the effectiveness of the CV777-based vaccine needs to be evaluated.",2013 Aug 15,"['Tian, Yufei', 'Yu, Zhijun', 'Cheng, Kaihui', 'Liu, Yuxiu', 'Huang, Jing', 'Xin, Yue', 'Li, Yuanguo', 'Fan, Shengtao', 'Wang, Tiecheng', 'Huang, Geng', 'Feng, Na', 'Yang, Zhenguo', 'Yang, Songtao', 'Gao, Yuwei', 'Xia, Xianzhu']",Viruses,,,True
b786e66932955124f073e42aec53ea4a0f0cbb9b,PMC,Global Causes of Diarrheal Disease Mortality in Children <5 Years of Age: A Systematic Review,http://dx.doi.org/10.1371/journal.pone.0072788,PMC3762858,24023773,CC0,"Estimation of pathogen-specific causes of child diarrhea deaths is needed to guide vaccine development and other prevention strategies. We did a systematic review of articles published between 1990 and 2011 reporting at least one of 13 pathogens in children <5 years of age hospitalized with diarrhea. We included 2011 rotavirus data from the Rotavirus Surveillance Network coordinated by WHO. We excluded studies conducted during diarrhea outbreaks that did not discriminate between inpatient and outpatient cases, reporting nosocomial infections, those conducted in special populations, not done with adequate methods, and rotavirus studies in countries where the rotavirus vaccine was used. Age-adjusted median proportions for each pathogen were calculated and applied to 712 000 deaths due to diarrhea in children under 5 years for 2011, assuming that those observed among children hospitalized for diarrhea represent those causing child diarrhea deaths. 163 articles and WHO studies done in 31 countries were selected representing 286 inpatient studies. Studies seeking only one pathogen found higher proportions for some pathogens than studies seeking multiple pathogens (e.g. 39% rotavirus in 180 single-pathogen studies vs. 20% in 24 studies with 5–13 pathogens, p<0·0001). The percentage of episodes for which no pathogen could be identified was estimated to be 34%; the total of all age-adjusted percentages for pathogens and no-pathogen cases was 138%. Adjusting all proportions, including unknowns, to add to 100%, we estimated that rotavirus caused 197 000 [Uncertainty range (UR) 110 000–295 000], enteropathogenic E. coli 79 000 (UR 31 000–146 000), calicivirus 71 000 (UR 39 000–113 000), and enterotoxigenic E. coli 42 000 (UR 20 000–76 000) deaths. Rotavirus, calicivirus, enteropathogenic and enterotoxigenic E. coli cause more than half of all diarrheal deaths in children <5 years in the world.",2013 Sep 4,"['Lanata, Claudio F.', 'Fischer-Walker, Christa L.', 'Olascoaga, Ana C.', 'Torres, Carla X.', 'Aryee, Martin J.', 'Black, Robert E.', None]",PLoS One,,,True
6ad08282a281d311d1a9e87b8085a6f0c968ad50,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,True
2734a77d07ccffecc6409adaf6ccaba349155d7a,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
7f24652f604c181ad124bbd90019abcf45637ad5,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
6277fc8f2d8452c4130e5ae1f27b1678ba075f53,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
007e45183f45c14370636a1eaa6c5531dbcda45f,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
c5970d7ff79c420af4349f7c1fd7a3032de32b70,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
70fc6334817c8db13b936a2b96a072a7355ccbce,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
89bb0f2d1c9c091ce0d5b246976fb0f97d4fb2bd,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
31a5e7e1ec03528f7ef6755f6619f4509b3df2cc,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
31ad311010df14ce34534e925cec26f499109285,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
aef400eac72623d01820a1b2ca11e49a81917416,PMC,Human Health Risk Assessment (HHRA) for Environmental Development and Transfer of Antibiotic Resistance,http://dx.doi.org/10.1289/ehp.1206316,PMC3764079,23838256,CC0,"Background: Only recently has the environment been clearly implicated in the risk of antibiotic resistance to clinical outcome, but to date there have been few documented approaches to formally assess these risks. Objective: We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of antibiotic treatment caused by antibiotic-resistant pathogens. Methods: The authors participated in a workshop held 4–8 March 2012 in Québec, Canada, to define the scope and objectives of an environmental assessment of antibiotic-resistance risks to human health. We focused on key elements of environmental-resistance-development “hot spots,” exposure assessment (unrelated to food), and dose response to characterize risks that may improve antibiotic-resistance management options. Discussion: Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental antibiotic resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental “hot spot” compartments; and c) modifying traditional dose–response approaches to address doses of ARB for various health outcomes and pathways. Conclusions: We propose that environmental aspects of antibiotic-resistance development be included in the processes of any HHRA addressing ARB. Because of limited available data, a multicriteria decision analysis approach would be a useful way to undertake an HHRA of environmental antibiotic resistance that informs risk managers. Citation: Ashbolt NJ, Amézquita A, Backhaus T, Borriello P, Brandt KK, Collignon P, Coors A, Finley R, Gaze WH, Heberer T, Lawrence JR, Larsson DG, McEwen SA, Ryan JJ, Schönfeld J, Silley P, Snape JR, Van den Eede C, Topp E. 2013. Human health risk assessment (HHRA) for environmental development and transfer of antibiotic resistance. Environ Health Perspect 121:993–1001; http://dx.doi.org/10.1289/ehp.1206316",2013 Sep 9,"['Ashbolt, Nicholas J.', 'Amézquita, Alejandro', 'Backhaus, Thomas', 'Borriello, Peter', 'Brandt, Kristian K.', 'Collignon, Peter', 'Coors, Anja', 'Finley, Rita', 'Gaze, William H.', 'Heberer, Thomas', 'Lawrence, John R.', 'Larsson, D.G. Joakim', 'McEwen, Scott A.', 'Ryan, James J.', 'Schönfeld, Jens', 'Silley, Peter', 'Snape, Jason R.', 'Van den Eede, Christel', 'Topp, Edward']",Environ Health Perspect,,,True
1842bb195a368132b3f4b433e1b1a71590fdc31e,PMC,In Vitro Infection of Pupae with Israeli Acute Paralysis Virus Suggests Disturbance of Transcriptional Homeostasis in Honey Bees (Apis mellifera),http://dx.doi.org/10.1371/journal.pone.0073429,PMC3764161,24039938,CC0,"The ongoing decline of honey bee health worldwide is a serious economic and ecological concern. One major contributor to the decline are pathogens, including several honey bee viruses. However, information is limited on the biology of bee viruses and molecular interactions with their hosts. An experimental protocol to test these systems was developed, using injections of Israeli Acute Paralysis Virus (IAPV) into honey bee pupae reared ex-situ under laboratory conditions. The infected pupae developed pronounced but variable patterns of disease. Symptoms varied from complete cessation of development with no visual evidence of disease to rapid darkening of a part or the entire body. Considerable differences in IAPV titer dynamics were observed, suggesting significant variation in resistance to IAPV among and possibly within honey bee colonies. Thus, selective breeding for virus resistance should be possible. Gene expression analyses of three separate experiments suggest IAPV disruption of transcriptional homeostasis of several fundamental cellular functions, including an up-regulation of the ribosomal biogenesis pathway. These results provide first insights into the mechanisms of IAPV pathogenicity. They mirror a transcriptional survey of honey bees afflicted with Colony Collapse Disorder and thus support the hypothesis that viruses play a critical role in declining honey bee health.",2013 Sep 5,"['Boncristiani, Humberto F.', 'Evans, Jay D.', 'Chen, Yanping', 'Pettis, Jeff', 'Murphy, Charles', 'Lopez, Dawn L.', 'Simone-Finstrom, Michael', 'Strand, Micheline', 'Tarpy, David R.', 'Rueppell, Olav']",PLoS One,,,True
57e9dad391ccc19e24be64df52865485c942858a,PMC,In Vitro Infection of Pupae with Israeli Acute Paralysis Virus Suggests Disturbance of Transcriptional Homeostasis in Honey Bees (Apis mellifera),http://dx.doi.org/10.1371/journal.pone.0073429,PMC3764161,24039938,CC0,"The ongoing decline of honey bee health worldwide is a serious economic and ecological concern. One major contributor to the decline are pathogens, including several honey bee viruses. However, information is limited on the biology of bee viruses and molecular interactions with their hosts. An experimental protocol to test these systems was developed, using injections of Israeli Acute Paralysis Virus (IAPV) into honey bee pupae reared ex-situ under laboratory conditions. The infected pupae developed pronounced but variable patterns of disease. Symptoms varied from complete cessation of development with no visual evidence of disease to rapid darkening of a part or the entire body. Considerable differences in IAPV titer dynamics were observed, suggesting significant variation in resistance to IAPV among and possibly within honey bee colonies. Thus, selective breeding for virus resistance should be possible. Gene expression analyses of three separate experiments suggest IAPV disruption of transcriptional homeostasis of several fundamental cellular functions, including an up-regulation of the ribosomal biogenesis pathway. These results provide first insights into the mechanisms of IAPV pathogenicity. They mirror a transcriptional survey of honey bees afflicted with Colony Collapse Disorder and thus support the hypothesis that viruses play a critical role in declining honey bee health.",2013 Sep 5,"['Boncristiani, Humberto F.', 'Evans, Jay D.', 'Chen, Yanping', 'Pettis, Jeff', 'Murphy, Charles', 'Lopez, Dawn L.', 'Simone-Finstrom, Michael', 'Strand, Micheline', 'Tarpy, David R.', 'Rueppell, Olav']",PLoS One,,,False
2fb74042460bf37f74e93a6ee3d7997e82a43bdb,PMC,In Vitro Infection of Pupae with Israeli Acute Paralysis Virus Suggests Disturbance of Transcriptional Homeostasis in Honey Bees (Apis mellifera),http://dx.doi.org/10.1371/journal.pone.0073429,PMC3764161,24039938,CC0,"The ongoing decline of honey bee health worldwide is a serious economic and ecological concern. One major contributor to the decline are pathogens, including several honey bee viruses. However, information is limited on the biology of bee viruses and molecular interactions with their hosts. An experimental protocol to test these systems was developed, using injections of Israeli Acute Paralysis Virus (IAPV) into honey bee pupae reared ex-situ under laboratory conditions. The infected pupae developed pronounced but variable patterns of disease. Symptoms varied from complete cessation of development with no visual evidence of disease to rapid darkening of a part or the entire body. Considerable differences in IAPV titer dynamics were observed, suggesting significant variation in resistance to IAPV among and possibly within honey bee colonies. Thus, selective breeding for virus resistance should be possible. Gene expression analyses of three separate experiments suggest IAPV disruption of transcriptional homeostasis of several fundamental cellular functions, including an up-regulation of the ribosomal biogenesis pathway. These results provide first insights into the mechanisms of IAPV pathogenicity. They mirror a transcriptional survey of honey bees afflicted with Colony Collapse Disorder and thus support the hypothesis that viruses play a critical role in declining honey bee health.",2013 Sep 5,"['Boncristiani, Humberto F.', 'Evans, Jay D.', 'Chen, Yanping', 'Pettis, Jeff', 'Murphy, Charles', 'Lopez, Dawn L.', 'Simone-Finstrom, Michael', 'Strand, Micheline', 'Tarpy, David R.', 'Rueppell, Olav']",PLoS One,,,False
3bcd3d1d3d50b169ecc0397bf956a8c04c76c2bc,PMC,In Vitro Infection of Pupae with Israeli Acute Paralysis Virus Suggests Disturbance of Transcriptional Homeostasis in Honey Bees (Apis mellifera),http://dx.doi.org/10.1371/journal.pone.0073429,PMC3764161,24039938,CC0,"The ongoing decline of honey bee health worldwide is a serious economic and ecological concern. One major contributor to the decline are pathogens, including several honey bee viruses. However, information is limited on the biology of bee viruses and molecular interactions with their hosts. An experimental protocol to test these systems was developed, using injections of Israeli Acute Paralysis Virus (IAPV) into honey bee pupae reared ex-situ under laboratory conditions. The infected pupae developed pronounced but variable patterns of disease. Symptoms varied from complete cessation of development with no visual evidence of disease to rapid darkening of a part or the entire body. Considerable differences in IAPV titer dynamics were observed, suggesting significant variation in resistance to IAPV among and possibly within honey bee colonies. Thus, selective breeding for virus resistance should be possible. Gene expression analyses of three separate experiments suggest IAPV disruption of transcriptional homeostasis of several fundamental cellular functions, including an up-regulation of the ribosomal biogenesis pathway. These results provide first insights into the mechanisms of IAPV pathogenicity. They mirror a transcriptional survey of honey bees afflicted with Colony Collapse Disorder and thus support the hypothesis that viruses play a critical role in declining honey bee health.",2013 Sep 5,"['Boncristiani, Humberto F.', 'Evans, Jay D.', 'Chen, Yanping', 'Pettis, Jeff', 'Murphy, Charles', 'Lopez, Dawn L.', 'Simone-Finstrom, Michael', 'Strand, Micheline', 'Tarpy, David R.', 'Rueppell, Olav']",PLoS One,,,False
2f132252da880c9c19d5548ef6ab4ac752a90244,PMC,Emergence of the Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1371/journal.ppat.1003595,PMC3764217,24039577,CC BY,,2013 Sep 5,"['Coleman, Christopher M.', 'Frieman, Matthew B.']",PLoS Pathog,,,True
b8e9fcc34571f9c29e04f9feb34197250556cb9a,PMC,"Mechanisms of protective immune responses induced by the Plasmodium falciparum circumsporozoite protein-based, self-assembling protein nanoparticle vaccine",http://dx.doi.org/10.1186/1475-2875-12-136,PMC3765086,23607541,CC BY,"BACKGROUND: A lack of defined correlates of immunity for malaria, combined with the inability to induce long-lived sterile immune responses in a human host, demonstrate a need for improved understanding of potentially protective immune mechanisms for enhanced vaccine efficacy. Protective sterile immunity (>90%) against the Plasmodium falciparum circumsporozoite protein (CSP) has been achieved using a transgenically modified Plasmodium berghei sporozoite (Tg-Pb/PfCSP) and a self-assembling protein nanoparticle (SAPN) vaccine presenting CSP epitopes (PfCSP-SAPN). Here, several possible mechanisms involved in the independently protective humoral and cellular responses induced following SAPN immunization are described. METHODS: Inbred mice were vaccinated with PfCSP-SAPN in PBS. Serum antibodies were harvested and effects on P. falciparum sporozoites mobility and integrity were examined using phase contrast microscopy. The functionality of SAPN-induced antibodies on inhibition of sporozoite invasion and growth within primary human hepatocytes was also examined. The internal processing of SAPN by bone marrow-derived dendritic cells (BMDDC), using organelle-specific, fluorescent-tagged antibody or gold-encapsulated SAPN, was observed using confocal or electron microscopy, respectively. RESULTS: The results of this work demonstrate that PfCSP-SAPN induces epitope-specific antibody titers, predominantly of the Th2 isotype IgG1, and that serum antibodies from PfCSP-SAPN-immunized mice appear to target P. falciparum sporozoites via the classical pathway of complement. This results in sporozoite death as indicated by cessation of motility and the circumsporozoite precipitation reaction. Moreover, PfCSP-SAPN-induced antibodies are able to inhibit wild-type P. falciparum sporozoite invasion and growth within cultured primary human hepatocytes. In addition, the observation that PfCSP-SAPN are processed (and presented) to the immune system by dendritic cells in a slow and continuous fashion via transporter associated with antigen processing (TAP) recruitment to the early endosome (EE), and have partially delayed processing through the endoplasmic reticulum, has the potential to induce the long-lived, effector memory CD8(+) T-cells as described previously. CONCLUSION: This paper describes the examination of humoral and cellular immune mechanisms induced by PfCSP-SAPN vaccination which result in sterile host protection against a transgenic P. berghei malaria sporozoite expressing the P. falciparum CSP, and which significantly inhibits native P. falciparum sporozoites from invading and developing within cultured human hepatocytes. These results may indicate the type and mode of action of protective antibodies needed to control P. falciparum sporozoites from infecting humans as well as a potential mechanism of induction of protective long-lived effector memory CD8(+) T-cells.",2013 Apr 22,"['McCoy, Margaret E', 'Golden, Hannah E', 'Doll, Tais APF', 'Yang, Yongkun', 'Kaba, Stephen A', 'Burkhard, Peter', 'Lanar, David E']",Malar J,,,True
7f9e15b30bfa7b75a43c5d9febf1b6f71240f80b,PMC,The TARGET cohort study protocol: a prospective primary care cohort study to derive and validate a clinical prediction rule to improve the targeting of antibiotics in children with respiratory tract illnesses,http://dx.doi.org/10.1186/1472-6963-13-322,PMC3765099,23958109,CC BY,"BACKGROUND: Children with respiratory tract infections are the single most frequent patient group to make use of primary care health care resources. The use of antibiotics remains highly prevalent in young children, but can lead to antimicrobial resistance as well as reinforcing the idea that parents should re-consult for similar symptoms. One of the main drivers of indiscriminate antimicrobial use is the lack of evidence for, and therefore uncertainty regarding, which children are at risk of poor outcome. This paper describes the protocol for the TARGET cohort study, which aims to derive and validate a clinical prediction rule to identify children presenting to primary care with respiratory tract infections who are at risk of hospitalisation. METHODS/DESIGN: The TARGET cohort study is a large, multicentre prospective observational study aiming to recruit 8,300 children aged ≥3 months and <16 years presenting to primary care with a cough and respiratory tract infection symptoms from 4 study centres (Bristol, London, Oxford and Southampton). Following informed consent, symptoms, signs and demographics will be measured. In around a quarter of children from the Bristol centre, a single sweep, dual bacterial-viral throat swab will be taken and parents asked to complete a symptom diary until the child is completely well or for 28 days, whichever is sooner. A review of medical notes including clinical history, re-consultation and hospitalisations will be undertaken. Multivariable logistic regression will be used to identify the independent clinical predictors of hospitalisation as well as the prognostic significance of upper respiratory tract microbes. The clinical prediction rule will be internally validated using various methods including bootstrapping. DISCUSSION: The clinical prediction rule for hospitalisation has the potential to help identify a small group of children for hospitalisation and a much larger group where hospitalisation is very unlikely and antibiotic prescribing would be less warranted. This study will also be the largest natural history study to date of children presenting to primary care with acute cough and respiratory tract infections, and will provide important information on symptom duration, re-consultations and the microbiology of the upper respiratory tract.",2013 Aug 17,"['Redmond, Niamh M', 'Davies, Rachel', 'Christensen, Hannah', 'Blair, Peter S', 'Lovering, Andrew M', 'Leeming, John P', 'Muir, Peter', 'Vipond, Barry', 'Thornton, Hannah', 'Fletcher, Margaret', 'Delaney, Brendan', 'Little, Paul', 'Thompson, Matthew', 'Peters, Tim J', 'Hay, Alastair D']",BMC Health Serv Res,,,True
8cc77f375b6cd2d7021976e3b6c43822f4243f3a,PMC,The TARGET cohort study protocol: a prospective primary care cohort study to derive and validate a clinical prediction rule to improve the targeting of antibiotics in children with respiratory tract illnesses,http://dx.doi.org/10.1186/1472-6963-13-322,PMC3765099,23958109,CC BY,"BACKGROUND: Children with respiratory tract infections are the single most frequent patient group to make use of primary care health care resources. The use of antibiotics remains highly prevalent in young children, but can lead to antimicrobial resistance as well as reinforcing the idea that parents should re-consult for similar symptoms. One of the main drivers of indiscriminate antimicrobial use is the lack of evidence for, and therefore uncertainty regarding, which children are at risk of poor outcome. This paper describes the protocol for the TARGET cohort study, which aims to derive and validate a clinical prediction rule to identify children presenting to primary care with respiratory tract infections who are at risk of hospitalisation. METHODS/DESIGN: The TARGET cohort study is a large, multicentre prospective observational study aiming to recruit 8,300 children aged ≥3 months and <16 years presenting to primary care with a cough and respiratory tract infection symptoms from 4 study centres (Bristol, London, Oxford and Southampton). Following informed consent, symptoms, signs and demographics will be measured. In around a quarter of children from the Bristol centre, a single sweep, dual bacterial-viral throat swab will be taken and parents asked to complete a symptom diary until the child is completely well or for 28 days, whichever is sooner. A review of medical notes including clinical history, re-consultation and hospitalisations will be undertaken. Multivariable logistic regression will be used to identify the independent clinical predictors of hospitalisation as well as the prognostic significance of upper respiratory tract microbes. The clinical prediction rule will be internally validated using various methods including bootstrapping. DISCUSSION: The clinical prediction rule for hospitalisation has the potential to help identify a small group of children for hospitalisation and a much larger group where hospitalisation is very unlikely and antibiotic prescribing would be less warranted. This study will also be the largest natural history study to date of children presenting to primary care with acute cough and respiratory tract infections, and will provide important information on symptom duration, re-consultations and the microbiology of the upper respiratory tract.",2013 Aug 17,"['Redmond, Niamh M', 'Davies, Rachel', 'Christensen, Hannah', 'Blair, Peter S', 'Lovering, Andrew M', 'Leeming, John P', 'Muir, Peter', 'Vipond, Barry', 'Thornton, Hannah', 'Fletcher, Margaret', 'Delaney, Brendan', 'Little, Paul', 'Thompson, Matthew', 'Peters, Tim J', 'Hay, Alastair D']",BMC Health Serv Res,,,False
3fb8269503a524e2257482ce479a05abd732ddfe,PMC,"Carcinoembryonic antigen (CEA)-related cell adhesion molecules are co-expressed in the human lung and their expression can be modulated in bronchial epithelial cells by non-typable Haemophilus influenzae, Moraxella catarrhalis, TLR3, and type I and II interferons",http://dx.doi.org/10.1186/1465-9921-14-85,PMC3765474,23941132,CC BY,"BACKGROUND: The carcinoembryonic antigen (CEA)-related cell adhesion molecules CEACAM1 (BGP, CD66a), CEACAM5 (CEA, CD66e) and CEACAM6 (NCA, CD66c) are expressed in human lung. They play a role in innate and adaptive immunity and are targets for various bacterial and viral adhesins. Two pathogens that colonize the normally sterile lower respiratory tract in patients with chronic obstructive pulmonary disease (COPD) are non-typable Haemophilus influenzae (NTHI) and Moraxella catarrhalis. Both pathogens bind to CEACAMs and elicit a variety of cellular reactions, including bacterial internalization, cell adhesion and apoptosis. METHODS: To analyze the (co-) expression of CEACAM1, CEACAM5 and CEACAM6 in different lung tissues with respect to COPD, smoking status and granulocyte infiltration, immunohistochemically stained paraffin sections of 19 donors were studied. To address short-term effects of cigarette smoke and acute inflammation, transcriptional regulation of CEACAM5, CEACAM6 and different CEACAM1 isoforms by cigarette smoke extract, interferons, Toll-like receptor agonists, and bacteria was tested in normal human bronchial epithelial (NHBE) cells by quantitative PCR. Corresponding CEACAM protein levels were determined by flow cytometry. RESULTS: Immunohistochemical analysis of lung sections showed the most frequent and intense staining for CEACAM1, CEACAM5 and CEACAM6 in bronchial and alveolar epithelium, but revealed no significant differences in connection with COPD, smoking status and granulocyte infiltration. In NHBE cells, mRNA expression of CEACAM1 isoforms CEACAM1-4L, CEACAM1-4S, CEACAM1-3L and CEACAM1-3S were up-regulated by interferons alpha, beta and gamma, as well as the TLR3 agonist polyinosinic:polycytidylic acid (poly I:C). Interferon-gamma also increased CEACAM5 expression. These results were confirmed on protein level by FACS analysis. Importantly, also NTHI and M. catarrhalis increased CEACAM1 mRNA levels. This effect was independent of the ability to bind to CEACAM1. The expression of CEACAM6 was not affected by any treatment or bacterial infection. CONCLUSIONS: While we did not find a direct correlation between CEACAM1 expression and COPD, the COPD-associated bacteria NTHi and M. catarrhalis were able to increase the expression of their own receptor on host cells. Further, the data suggest a role for CEACAM1 and CEACAM5 in the phenomenon of increased host susceptibility to bacterial infection upon viral challenge in the human respiratory tract.",2013 Aug 14,"['Klaile, Esther', 'Klassert, Tilman E', 'Scheffrahn, Inka', 'Müller, Mario M', 'Heinrich, Annina', 'Heyl, Kerstin A', 'Dienemann, Hendrik', 'Grünewald, Christiane', 'Bals, Robert', 'Singer, Bernhard B', 'Slevogt, Hortense']",Respir Res,,,True
39ab5e6b24f55e696076c53f96fc5704ff3ff0f0,PMC,Establishment of feline intestinal epithelial cell cultures for the propagation and study of feline enteric coronaviruses,http://dx.doi.org/10.1186/1297-9716-44-71,PMC3765525,23964891,CC BY,"Feline infectious peritonitis (FIP) is the most feared infectious cause of death in cats, induced by feline infectious peritonitis virus (FIPV). This coronavirus is a virulent mutant of the harmless, ubiquitous feline enteric coronavirus (FECV). To date, feline coronavirus (FCoV) research has been hampered by the lack of susceptible cell lines for the propagation of serotype I FCoVs. In this study, long-term feline intestinal epithelial cell cultures were established from primary ileocytes and colonocytes by simian virus 40 (SV40) T-antigen- and human Telomerase Reverse Transcriptase (hTERT)-induced immortalization. Subsequently, these cultures were evaluated for their usability in FCoV research. Firstly, the replication capacity of the serotype II strains WSU 79–1683 and WSU 79–1146 was studied in the continuous cultures as was done for the primary cultures. In accordance with the results obtained in primary cultures, FCoV WSU 79–1683 still replicated significantly more efficient compared to FCoV WSU 79–1146 in both continuous cultures. In addition, the cultures were inoculated with faecal suspensions from healthy cats and with faecal or tissue suspensions from FIP cats. The cultures were susceptible to infection with different serotype I enteric strains and two of these strains were further propagated. No infection was seen in cultures inoculated with FIPV tissue homogenates. In conclusion, a new reliable model for FCoV investigation and growth of enteric field strains was established. In contrast to FIPV strains, FECVs showed a clear tropism for intestinal epithelial cells, giving an explanation for the observation that FECV is the main pathotype circulating among cats.",2013 Aug 21,"['Desmarets, Lowiese MB', 'Theuns, Sebastiaan', 'Olyslaegers, Dominique AJ', 'Dedeurwaerder, Annelike', 'Vermeulen, Ben L', 'Roukaerts, Inge DM', 'Nauwynck, Hans J']",Vet Res,,,True
14c6dff031b3bcf8a7ea8486965b1dd888cf46a4,PMC,A safe and convenient pseudovirus-based inhibition assay to detect neutralizing antibodies and screen for viral entry inhibitors against the novel human coronavirus MERS-CoV,http://dx.doi.org/10.1186/1743-422X-10-266,PMC3765664,23978242,CC BY,"BACKGROUND: Evidence points to the emergence of a novel human coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), which causes a severe acute respiratory syndrome (SARS)-like disease. In response, the development of effective vaccines and therapeutics remains a clinical priority. To accomplish this, it is necessary to evaluate neutralizing antibodies and screen for MERS-CoV entry inhibitors. METHODS: In this study, we produced a pseudovirus bearing the full-length spike (S) protein of MERS-CoV in the Env-defective, luciferase-expressing HIV-1 backbone. We then established a pseudovirus-based inhibition assay to detect neutralizing antibodies and anti-MERS-CoV entry inhibitors. RESULTS: Our results demonstrated that the generated MERS-CoV pseudovirus allows for single-cycle infection of a variety of cells expressing dipeptidyl peptidase-4 (DPP4), the confirmed receptor for MERS-CoV. Consistent with the results from a live MERS-CoV-based inhibition assay, the antisera of mice vaccinated with a recombinant protein containing receptor-binding domain (RBD, residues 377–662) of MERS-CoV S fused with Fc of human IgG exhibited neutralizing antibody response against infection of MERS-CoV pseudovirus. Furthermore, one small molecule HIV entry inhibitor targeting gp41 (ADS-J1) and the 3-hydroxyphthalic anhydride-modified human serum albumin (HP-HSA) could significantly inhibit MERS-CoV pseudovirus infection. CONCLUSION: Taken together, the established MERS-CoV inhibition assay is a safe and convenient pseudovirus-based alternative to BSL-3 live-virus restrictions and can be used to rapidly screen MERS-CoV entry inhibitors, as well as evaluate vaccine-induced neutralizing antibodies against the highly pathogenic MERS-CoV.",2013 Aug 26,"['Zhao, Guangyu', 'Du, Lanying', 'Ma, Cuiqing', 'Li, Ye', 'Li, Lin', 'Poon, Vincent KM', 'Wang, Lili', 'Yu, Fei', 'Zheng, Bo-Jian', 'Jiang, Shibo', 'Zhou, Yusen']",Virol J,,,True
cee73a9e8367f60e1149b8db0b8a00a780c84d9d,PMC,Chikungunya virus capsid protein contains nuclear import and export signals,http://dx.doi.org/10.1186/1743-422X-10-269,PMC3765696,23984714,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is an alphavirus of the Togaviridae family. After autoproteolytic cleavage, the CHIKV capsid protein (CP) is involved in RNA binding and assembly of the viral particle. The monomeric CP is approximately 30 kDa in size and is small enough for passive transport through nuclear pores. Some alphaviruses are found to harbor nuclear localization signals (NLS) and transport of these proteins between cellular compartments was shown to be energy dependent. The active nuclear import of cytoplasmic proteins is mediated by karyopherins and their export by exportins. As nuclear and cytoplasmic trafficking may play a role in the life cycle of CHIKV, we have sought to identify nuclear localization and nuclear export signals in CHIKV CP in a virus-free system. METHODS: EGFP-fusion proteins of CHIKV CP and mutants thereof were created and used to monitor their intracellular localization. Binding of cellular proteins was confirmed in pull-down assays with purified CP using co-immuoprecipitation. Nuclear localization was demonstrated in a virus-free system using fluorescence microscopy. RESULTS: Here we show that CHIKV CP is a nuclear-cytoplasmic shuttling protein with an active NLS that binds to karyopherin α (Karα) for its nuclear translocation. We also found that the Karα4 C-terminal NLS binding site is sufficient for this interaction. We further demonstrate that CHIKV CP interacts directly with the export receptor CRM1 to transport this viral protein out of the nucleus via a nuclear export signal (NES). The CHIKV CP NES was mapped between amino acids 143 and 155 of CP. Deduced from in silico analyses we found that the NES has a mode of binding similar to the snurportin-1 CRM1 complex. CONCLUSIONS: We were able to show that in a virus-free system that the CHIKV capsid protein contains both, a NLS and a NES, and that it is actively transported between the cytoplasma and the nucleus. We conclude that CHIKV CP has the ability to shuttle via interaction with karyopherins for its nuclear import and, vice versa, by CRM1-dependent nuclear export.",2013 Aug 28,"['Thomas, Saijo', 'Rai, Jagdish', 'John, Lijo', 'Schaefer, Stephan', 'Pützer, Brigitte M', 'Herchenröder, Ottmar']",Virol J,,,True
cad994637f061356cd5ea11a7570b2f5ad38ed47,PMC,Estimating Potential Infection Transmission Routes in Hospital Wards Using Wearable Proximity Sensors,http://dx.doi.org/10.1371/journal.pone.0073970,PMC3770639,24040129,CC BY,"BACKGROUND: Contacts between patients, patients and health care workers (HCWs) and among HCWs represent one of the important routes of transmission of hospital-acquired infections (HAI). A detailed description and quantification of contacts in hospitals provides key information for HAIs epidemiology and for the design and validation of control measures. METHODS AND FINDINGS: We used wearable sensors to detect close-range interactions (“contacts”) between individuals in the geriatric unit of a university hospital. Contact events were measured with a spatial resolution of about 1.5 meters and a temporal resolution of 20 seconds. The study included 46 HCWs and 29 patients and lasted for 4 days and 4 nights. 14,037 contacts were recorded overall, 94.1% of which during daytime. The number and duration of contacts varied between mornings, afternoons and nights, and contact matrices describing the mixing patterns between HCW and patients were built for each time period. Contact patterns were qualitatively similar from one day to the next. 38% of the contacts occurred between pairs of HCWs and 6 HCWs accounted for 42% of all the contacts including at least one patient, suggesting a population of individuals who could potentially act as super-spreaders. CONCLUSIONS: Wearable sensors represent a novel tool for the measurement of contact patterns in hospitals. The collected data can provide information on important aspects that impact the spreading patterns of infectious diseases, such as the strong heterogeneity of contact numbers and durations across individuals, the variability in the number of contacts during a day, and the fraction of repeated contacts across days. This variability is however associated with a marked statistical stability of contact and mixing patterns across days. Our results highlight the need for such measurement efforts in order to correctly inform mathematical models of HAIs and use them to inform the design and evaluation of prevention strategies.",2013 Sep 11,"['Vanhems, Philippe', 'Barrat, Alain', 'Cattuto, Ciro', 'Pinton, Jean-François', 'Khanafer, Nagham', 'Régis, Corinne', 'Kim, Byeul-a', 'Comte, Brigitte', 'Voirin, Nicolas']",PLoS One,,,True
794b9541d676d262ebca65c8b3f1d7ca64d4441f,PMC,Molecular epidemiology of respiratory viruses in virus-induced asthma,http://dx.doi.org/10.3389/fmicb.2013.00278,PMC3771312,24062735,CC BY,"Acute respiratory illness (ARI) due to various viruses is not only the most common cause of upper respiratory infection in humans but is also a major cause of morbidity and mortality, leading to diseases such as bronchiolitis and pneumonia. Previous studies have shown that respiratory syncytial virus (RSV), human rhinovirus (HRV), human metapneumovirus (HMPV), human parainfluenza virus (HPIV), and human enterovirus infections may be associated with virus-induced asthma. For example, it has been suggested that HRV infection is detected in the acute exacerbation of asthma and infection is prolonged. Thus it is believed that the main etiological cause of asthma is ARI viruses. Furthermore, the number of asthma patients in most industrial countries has greatly increased, resulting in a morbidity rate of around 10-15% of the population. However, the relationships between viral infections, host immune response, and host factors in the pathophysiology of asthma remain unclear. To gain a better understanding of the epidemiology of virus-induced asthma, it is important to assess both the characteristics of the viruses and the host defense mechanisms. Molecular epidemiology enables us to understand the pathogenesis of microorganisms by identifying specific pathways, molecules, and genes that influence the risk of developing a disease. However, the epidemiology of various respiratory viruses associated with virus-induced asthma is not fully understood. Therefore, in this article, we review molecular epidemiological studies of RSV, HRV, HPIV, and HMPV infection associated with virus-induced asthma.",2013 Sep 12,"['Tsukagoshi, Hiroyuki', 'Ishioka, Taisei', 'Noda, Masahiro', 'Kozawa, Kunihisa', 'Kimura, Hirokazu']",Front Microbiol,,,True
39d94b291715335c79664305706e67a752304121,PMC,"Outcome Risk Factors during Respiratory Infections in a Paediatric Ward in Antananarivo, Madagascar 2010–2012",http://dx.doi.org/10.1371/journal.pone.0072839,PMC3771918,24069161,CC BY,"BACKGROUND: Acute respiratory infections are a leading cause of infectious disease-related morbidity, hospitalisation and mortality among children worldwide, and particularly in developing countries. In these low-income countries, most patients with acute respiratory infection (ARI), whether it is mild or severe, are still treated empirically. The aim of the study was to evaluate the risk factors associated with the evolution and outcome of respiratory illnesses in patients aged under 5 years old. MATERIALS AND METHODS: We conducted a prospective study in a paediatric ward in Antananarivo from November 2010 to July 2012 including patients under 5 years old suffering from respiratory infections. We collected demographic, socio-economic, clinical and epidemiological data, and samples for laboratory analysis. Deaths, rapid progression to respiratory distress during hospitalisation, and hospitalisation for more than 10 days were considered as severe outcomes. We used multivariate analysis to study the effects of co-infections. RESULTS: From November 2010 to July 2012, a total of 290 patients were enrolled. Co-infection was found in 192 patients (70%). Co-infections were more frequent in children under 36 months, with a significant difference for the 19–24 month-old group (OR: 8.0). Sixty-nine percent (230/290) of the patients recovered fully and without any severe outcome during hospitalisation; the outcome was scored as severe for 60 children and nine patients (3%) died. Risk factors significantly associated with worsening evolution during hospitalisation (severe outcome) were admission at age under 6 months (OR = 5.3), comorbidity (OR = 4.6) and low household income (OR = 4.1). CONCLUSION: Co-mordidity, low-income and age under 6 months increase the risk of severe outcome for children infected by numerous respiratory pathogens. These results highlight the need for implementation of targeted public health policy to reduce the contribution of respiratory diseases to childhood morbidity and mortality in low income countries.",2013 Sep 12,"['Rajatonirina, Soatiana', 'Razanajatovo, Norosoa Harline', 'Ratsima, Elisoa Hariniana', 'Orelle, Arnaud', 'Ratovoson, Rila', 'Andrianirina, Zo Zafitsara', 'Andriatahina, Todisoa', 'Ramparany, Lovasoa', 'Herindrainy, Perlinot', 'Randrianirina, Frédérique', 'Heraud, Jean-Michel', 'Richard, Vincent']",PLoS One,,,True
04cf308cfa2f72131ecbb07bacb894bab15aa66e,PMC,"A Fusion-Inhibiting Peptide against Rift Valley Fever Virus Inhibits Multiple, Diverse Viruses",http://dx.doi.org/10.1371/journal.pntd.0002430,PMC3772029,24069485,CC0,"For enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. This fusion process is mediated by at least three classes of fusion proteins (Class I, II, and III) based on the protein sequence and structure. For Rift Valley fever virus (RVFV), the glycoprotein Gc (Class II fusion protein) mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. Here, we show that peptides analogous to the RVFV Gc stem region inhibited RVFV infectivity in cell culture by inhibiting the fusion process. Further, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola virus), Class II (Andes virus), or Class III (vesicular stomatitis virus) fusion proteins using this single peptide. Our findings are consistent with an inhibition mechanism similar to that proposed for stem peptide fusion inhibitors of dengue virus in which the RVFV inhibitory peptide first binds to both the virion and cell membranes, allowing it to traffic with the virus into the endocytic pathway. Upon acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion of the viral and endocytic membranes, thus inhibiting viral infection. These results could provide novel insights into conserved features among the three classes of viral fusion proteins and offer direction for the future development of broadly active fusion inhibitors.",2013 Sep 12,"['Koehler, Jeffrey W.', 'Smith, Jeffrey M.', 'Ripoll, Daniel R.', 'Spik, Kristin W.', 'Taylor, Shannon L.', 'Badger, Catherine V.', 'Grant, Rebecca J.', 'Ogg, Monica M.', 'Wallqvist, Anders', 'Guttieri, Mary C.', 'Garry, Robert F.', 'Schmaljohn, Connie S.']",PLoS Negl Trop Dis,,,True
0efede5fe4185af68b00ac20b99399af133e80bb,PMC,"Transcriptome Analysis of Human Peripheral Blood Mononuclear Cells Exposed to Lassa Virus and to the Attenuated Mopeia/Lassa Reassortant 29 (ML29), a Vaccine Candidate",http://dx.doi.org/10.1371/journal.pntd.0002406,PMC3772037,24069471,CC0,"Lassa virus (LASV) is the causative agent of Lassa Fever and is responsible for several hundred thousand infections and thousands of deaths annually in West Africa. LASV and the non-pathogenic Mopeia virus (MOPV) are both rodent-borne African arenaviruses. A live attenuated reassortant of MOPV and LASV, designated ML29, protects rodents and primates from LASV challenge and appears to be more attenuated than MOPV. To gain better insight into LASV-induced pathology and mechanism of attenuation we performed gene expression profiling in human peripheral blood mononuclear cells (PBMC) exposed to LASV and the vaccine candidate ML29. PBMC from healthy human subjects were exposed to either LASV or ML29. Although most PBMC are non-permissive for virus replication, they remain susceptible to signal transduction by virus particles. Total RNA was extracted and global gene expression was evaluated during the first 24 hours using high-density microarrays. Results were validated using RT-PCR, flow cytometry and ELISA. LASV and ML29 elicited differential expression of interferon-stimulated genes (ISG), as well as genes involved in apoptosis, NF-kB signaling and the coagulation pathways. These genes could eventually serve as biomarkers to predict disease outcomes. The remarkable differential expression of thrombomodulin, a key regulator of inflammation and coagulation, suggests its involvement with vascular abnormalities and mortality in Lassa fever disease.",2013 Sep 12,"['Zapata, Juan Carlos', 'Carrion, Ricardo', 'Patterson, Jean L.', 'Crasta, Oswald', 'Zhang, Yan', 'Mani, Sachin', 'Jett, Marti', 'Poonia, Bhawna', 'Djavani, Mahmoud', 'White, David M.', 'Lukashevich, Igor S.', 'Salvato, Maria S.']",PLoS Negl Trop Dis,,,True
6c9d5c49fd907d0380d25e4df6cac63b00bce66b,PMC,A Neutralizing Monoclonal Antibody Targeting the Acid-Sensitive Region in Chikungunya Virus E2 Protects from Disease,http://dx.doi.org/10.1371/journal.pntd.0002423,PMC3772074,24069479,CC BY,"The mosquito-borne alphavirus, chikungunya virus (CHIKV), has recently reemerged, producing the largest epidemic ever recorded for this virus, with up to 6.5 million cases of acute and chronic rheumatic disease. There are currently no licensed vaccines for CHIKV and current anti-inflammatory drug treatment is often inadequate. Here we describe the isolation and characterization of two human monoclonal antibodies, C9 and E8, from CHIKV infected and recovered individuals. C9 was determined to be a potent virus neutralizing antibody and a biosensor antibody binding study demonstrated it recognized residues on intact CHIKV VLPs. Shotgun mutagenesis alanine scanning of 98 percent of the residues in the E1 and E2 glycoproteins of CHIKV envelope showed that the epitope bound by C9 included amino-acid 162 in the acid-sensitive region (ASR) of the CHIKV E2 glycoprotein. The ASR is critical for the rearrangement of CHIKV E2 during fusion and viral entry into host cells, and we predict that C9 prevents these events from occurring. When used prophylactically in a CHIKV mouse model, C9 completely protected against CHIKV viremia and arthritis. We also observed that when administered therapeutically at 8 or 18 hours post-CHIKV challenge, C9 gave 100% protection in a pathogenic mouse model. Given that targeting this novel neutralizing epitope in E2 can potently protect both in vitro and in vivo, it is likely to be an important region both for future antibody and vaccine-based interventions against CHIKV.",2013 Sep 12,"['Selvarajah, Suganya', 'Sexton, Nicole R.', 'Kahle, Kristen M.', 'Fong, Rachel H.', 'Mattia, Kimberly-Anne', 'Gardner, Joy', 'Lu, Kai', 'Liss, Nathan M.', 'Salvador, Beatriz', 'Tucker, David F.', 'Barnes, Trevor', 'Mabila, Manu', 'Zhou, Xiangdong', 'Rossini, Giada', 'Rucker, Joseph B.', 'Sanders, David Avram', 'Suhrbier, Andreas', 'Sambri, Vittorio', 'Michault, Alain', 'Muench, Marcus O.', 'Doranz, Benjamin J.', 'Simmons, Graham']",PLoS Negl Trop Dis,,,True
d4ea57e72c426571255c1c45861db4c6b46b95d5,PMC,Pathogenic Mouse Hepatitis Virus or Poly(I:C) Induce IL-33 in Hepatocytes in Murine Models of Hepatitis,http://dx.doi.org/10.1371/journal.pone.0074278,PMC3772926,24058536,CC BY,"The IL-33/ST2 axis is known to be involved in liver pathologies. Although, the IL-33 levels increased in sera of viral hepatitis patients in human, the cellular sources of IL-33 in viral hepatitis remained obscure. Therefore, we aimed to investigate the expression of IL-33 in murine fulminant hepatitis induced by a Toll like receptor (TLR3) viral mimetic, poly(I:C) or by pathogenic mouse hepatitis virus (L2-MHV3). The administration of poly(I:C) plus D-galactosamine (D-GalN) in mice led to acute liver injury associated with the induction of IL-33 expression in liver sinusoidal endothelial cells (LSEC) and vascular endothelial cells (VEC), while the administration of poly(I:C) alone led to hepatocyte specific IL-33 expression in addition to vascular IL-33 expression. The hepatocyte-specific IL-33 expression was down-regulated in NK-depleted poly(I:C) treated mice suggesting a partial regulation of IL-33 by NK cells. The CD1d KO (NKT deficient) mice showed hepatoprotection against poly(I:C)-induced hepatitis in association with increased number of IL-33 expressing hepatocytes in CD1d KO mice than WT controls. These results suggest that hepatocyte-specific IL-33 expression in poly(I:C) induced liver injury was partially dependent of NK cells and with limited role of NKT cells. In parallel, the L2-MHV3 infection in mice induced fulminant hepatitis associated with up-regulated IL-33 expression as well as pro-inflammatory cytokine microenvironment in liver. The LSEC and VEC expressed inducible expression of IL-33 following L2-MHV3 infection but the hepatocyte-specific IL-33 expression was only evident between 24 to 32h of post infection. In conclusion, the alarmin cytokine IL-33 was over-expressed during fulminant hepatitis in mice with LSEC, VEC and hepatocytes as potential sources of IL-33.",2013 Sep 13,"['Arshad, Muhammad Imran', 'Patrat-Delon, Solène', 'Piquet-Pellorce, Claire', 'L’Helgoualc’h, Annie', 'Rauch, Michel', 'Genet, Valentine', 'Lucas-Clerc, Catherine', 'Bleau, Christian', 'Lamontagne, Lucie', 'Samson, Michel']",PLoS One,,,True
aef63beff452ee2eee54c7d60770dccf59890568,PMC,The Effectiveness and Mechanism of Toona sinensis Extract Inhibit Attachment of Pandemic Influenza A (H1N1) Virus,http://dx.doi.org/10.1155/2013/479718,PMC3773900,24073006,CC BY,"TSL-1 is a fraction of the aqueous extract from the tender leaf of Toona sinensis Roem, a nutritious vegetable. The pandemic influenza A (H1N1) virus is a recently described, rapidly contagious respiratory pathogen which can cause acute respiratory distress syndrome (ARDS) and poses a major public health threat. In this study, we found that TSL-1 inhibited viral yields on MDCK plaque formation by pandemic influenza A (H1N1) virus on infected A549 cells with high selectivity index. Meanwhile, TSL-1 also suppressed viral genome loads in infected A549 cells, quantified by qRT-PCR. This study further demonstrated that TSL-1 inhibited pandemic influenza A (H1N1) virus activity through preventing attachment of A549 cells but not penetration. TSL-1 inhibited viral attachment through significant downregulation of adhesion molecules and chemokines (VCAM-1, ICAM-1, E-selectin, IL-8, and fractalkine) compared to Amantadine. Our results suggest that TSL-1 may be used as an alternative treatment and prophylaxis against pandemic influenza A (H1N1) virus.",2013 Sep 2,"['You, Huey-Ling', 'Chen, Chung-Jen', 'Eng, Hock-Liew', 'Liao, Pei-Lin', 'Huang, Sheng-Teng']",Evid Based Complement Alternat Med,,,True
593d2241563c6bf2e57327ce40e7e83dacbd80fc,PMC,A Simple Methodology for Conversion of Mouse Monoclonal Antibody to Human-Mouse Chimeric Form,http://dx.doi.org/10.1155/2013/716961,PMC3775440,24078817,CC BY,"Passive immunotherapy has mainly been used as a therapy against cancer and inflammatory conditions. Recent studies have shown that monoclonal antibody-(mAb-) based passive immunotherapy is a promising approach to combat virus infection. Specific mouse mAbs can be routinely generated in large amounts with the use of hybridoma technology but these cannot be used for therapy in human beings due to their immunogenicity. Therefore, the development of chimeric and humanized mAbs is important for therapeutic purpose. This is facilitated by a variety of molecular techniques like recombinant DNA technology and the better understanding of the structure and function of antibody. The human-mouse chimeric forms allow detailed analysis of the mechanism of inhibition and the potential for therapeutic applications. Here, a step-by-step description of the conversion process will be described. The commercial availability of the reagents required in each step means that this experimentation can be easily set up in research laboratories.",2013 Sep 2,"['Dang, Vinh T.', 'Mandakhalikar, Kedar D.', 'Ng, Oi-Wing', 'Tan, Yee-Joo']",Clin Dev Immunol,,,True
062a18fe6bcaad19bd60d8b47d3287079a915545,PMC,Clinical Features and Factors Associated with Outcomes of Patients Infected with a Novel Influenza A (H7N9) Virus: A Preliminary Study,http://dx.doi.org/10.1371/journal.pone.0073362,PMC3775774,24069191,CC BY,"OBJECTIVE: The present study aimed to analyze clinical features and factors associated with treatment outcomes of H7N9 influenza A virus infection. METHODS: The clinical progress in 18 H7N9-infected patients was monitored and recorded. The clinical features of H7N9 infection were noted and factors associated with treatment outcomes were analyzed by univariate analyses. RESULTS: The average ages of patients in recovered and critical conditions were 67.0±10.83 years and 72.75±12.0 years, respectively. Renal insufficiency developed more frequently in critically ill patients (P = 0.023). The duration of traditional Chinese medicine (TCM) therapy was longer in recovered patients than in critically ill patients (P = 0.01). Laboratory tests showed that levels of C-reactive protein, serum creatinine, and myoglobin were significantly higher in critically ill patients than in recovered patients (P = 0.011, 0.04, and 0.016, respectively). Meanwhile, levels of all T cell subsets examined including total CD3(+), CD4(+), CD8(+), and CD45(+) T cells were lower in critically ill patients than in recovered patients (P = 0.033, 0.059, 0.015, and 0.039, respectively). Logistic regression analysis demonstrated that C-reactive protein level, myoglobin level and TCM therapy duration were likely associated with treatment outcomes of H7N9 infection (P = 0.032, 0.041 and 0.017, respectively). CONCLUSION: Elderly people may have increased risk for H7N9 virus infection. T cell-mediated responses play an important role in defense against the H7N9 virus. C-reactive protein level, myoglobin level and TCM duration may be associated with treatment outcomes of H7N9 infection.",2013 Sep 17,"['Chen, Xiaorong', 'Yang, Zongguo', 'Lu, Yunfei', 'Xu, Qingnian', 'Wang, Qiang', 'Chen, Liang']",PLoS One,,,True
bd7f96581b36339bff8aca7e50e1b91f333fc00e,PMC,The political economy of healthcare reform in China: negotiating public and private,http://dx.doi.org/10.1186/2193-1801-2-448,PMC3776089,24052932,CC BY,"China’s healthcare system is experiencing significant growth from expanded government-backed insurance, greater public-sector spending on hospitals, and the introduction of private insurance and for-profit clinics. An incremental reform process has sought to develop market incentives for medical innovation and liberalize physician compensation and hospital finance while continuing to keep basic care affordable to a large population that pays for many components of care out-of-pocket. Additional changes presently under consideration by policymakers are likely to further restructure insurance and the delivery of care and will alter competitive dynamics in major healthcare industries, notably pharmaceuticals, medical devices, and diagnostic testing. This article describes the institutional history of China’s healthcare system and identifies dilemmas emerging as the country negotiates divisions between public and private in healthcare. Building on this analysis, the article considers opportunities for public-private partnerships and greater systems integration to reconcile otherwise incommensurable approaches to rewarding innovation and improving access. The article concludes with observations on the public function of health insurance and its significance to further development of China’s healthcare system.",2013 Sep 10,"Daemmrich, Arthur",Springerplus,,,True
0d8784d230453109b9340461f2692f0f2d048927,PMC,Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells,http://dx.doi.org/10.1371/journal.pone.0075831,PMC3776769,24058703,CC BY,"Recently, one of the interferon-induced transmembrane (IFITM) family proteins, IFITM3, has become an important target for the activity against influenza A (H1N1) virus infection. In this protein, a post-translational modification by fatty acids covalently attached to cysteine, termed S-palmitoylation, plays a crucial role for the antiviral activity. IFITM3 possesses three cysteine residues for the S-palmitoylation in the first transmembrane (TM1) domain and in the cytoplasmic (CP) loop. Because these cysteines are well conserved in the mammalian IFITM family proteins, the S-palmitoylation on these cysteines is significant for their functions. IFITM5 is another IFITM family protein and interacts with the FK506-binding protein 11 (FKBP11) to form a higher-order complex in osteoblast cells, which induces the expression of immunologically relevant genes. In this study, we investigated the role played by S-palmitoylation of IFITM5 in its interaction with FKBP11 in the cells, because this interaction is a key process for the gene expression. Our investigations using an established reporter, 17-octadecynoic acid (17-ODYA), and an inhibitor for the S-palmitoylation, 2-bromopalmitic acid (2BP), revealed that IFITM5 was S-palmitoylated in addition to IFITM3. Specifically, we found that cysteine residues in the TM1 domain and in the CP loop were S-palmitoylated in IFITM5. Then, we revealed by immunoprecipitation and western blot analyses that the interaction of IFITM5 with FKBP11 was inhibited in the presence of 2BP. The mutant lacking the S-palmitoylation site in the TM1 domain lost the interaction with FKBP11. These results indicate that the S-palmitoylation on IFITM5 promotes the interaction with FKBP11. Finally, we investigated bone nodule formation in osteoblast cells in the presence of 2BP, because IFITM5 was originally identified as a bone formation factor. The experiment resulted in a morphological aberration of the bone nodule. This also indicated that the S-palmitoylation contributes to bone formation.",2013 Sep 18,"['Tsukamoto, Takashi', 'Li, Xianglan', 'Morita, Hiromi', 'Minowa, Takashi', 'Aizawa, Tomoyasu', 'Hanagata, Nobutaka', 'Demura, Makoto']",PLoS One,,,True
4bd41e4fe399ecfd7456792b11f51979999b4d1e,PMC,Hepatitis C Virus Replication and Golgi Function in Brefeldin A-Resistant Hepatoma-Derived Cells,http://dx.doi.org/10.1371/journal.pone.0074491,PMC3776844,24058576,CC BY,"Recent reports indicate that the replication of hepatitis C virus (HCV) depends on the GBF1-Arf1-COP-I pathway. We generated Huh-7-derived cell lines resistant to brefeldin A (BFA), which is an inhibitor of this pathway. The resistant cell lines could be sorted into two phenotypes regarding BFA-induced toxicity, inhibition of albumin secretion, and inhibition of HCV infection. Two cell lines were more than 100 times more resistant to BFA than the parental Huh-7 cells in these 3 assays. This resistant phenotype was correlated with the presence of a point mutation in the Sec7 domain of GBF1, which is known to impair the binding of BFA. Surprisingly, the morphology of the cis-Golgi of these cells remained sensitive to BFA at concentrations of the drug that allowed albumin secretion, indicating a dichotomy between the phenotypes of secretion and Golgi morphology. Cells of the second group were about 10 times more resistant than parental Huh-7 cells to the BFA-induced toxicity. The EC(50) for albumin secretion was only 1.5–1.8 fold higher in these cells than in Huh-7 cells. However their level of secretion in the presence of inhibitory doses of BFA was 5 to 15 times higher. Despite this partially effective secretory pathway in the presence of BFA, the HCV infection was almost as sensitive to BFA as in Huh-7 cells. This suggests that the function of GBF1 in HCV replication does not simply reflect its role of regulator of the secretory pathway of the host cell. Thus, our results confirm the involvement of GBF1 in HCV replication, and suggest that GBF1 might fulfill another function, in addition to the regulation of the secretory pathway, during HCV replication.",2013 Sep 18,"['Farhat, Rayan', 'Goueslain, Lucie', 'Wychowski, Czeslaw', 'Belouzard, Sandrine', 'Fénéant, Lucie', 'Jackson, Catherine L.', 'Dubuisson, Jean', 'Rouillé, Yves']",PLoS One,,,True
45dd7b43349a7cd110254e46282dd4968dcdffbe,PMC,Analysis of the Host Transcriptome from Demyelinating Spinal Cord of Murine Coronavirus-Infected Mice,http://dx.doi.org/10.1371/journal.pone.0075346,PMC3776850,24058676,CC BY,"Persistent infection of the mouse central nervous system (CNS) with mouse hepatitis virus (MHV) induces a demyelinating disease pathologically similar to multiple sclerosis and is therefore used as a model system. There is little information regarding the host factors that correlate with and contribute to MHV-induced demyelination. Here, we detail the genes and pathways associated with MHV-induced demyelinating disease in the spinal cord. High-throughput sequencing of the host transcriptome revealed that demyelination is accompanied by numerous transcriptional changes indicative of immune infiltration as well as changes in the cytokine milieu and lipid metabolism. We found evidence that a Th1-biased cytokine/chemokine response and eicosanoid-derived inflammation accompany persistent MHV infection and that antigen presentation is ongoing. Interestingly, increased expression of genes involved in lipid transport, processing, and catabolism, including some with known roles in neurodegenerative diseases, coincided with demyelination. Lastly, expression of several genes involved in osteoclast or bone-resident macrophage function, most notably TREM2 and DAP12, was upregulated in persistently infected mouse spinal cord. This study highlights the complexity of the host antiviral response, which accompany MHV-induced demyelination, and further supports previous findings that MHV-induced demyelination is immune-mediated. Interestingly, these data suggest a parallel between bone reabsorption by osteoclasts and myelin debris clearance by microglia in the bone and the CNS, respectively. To our knowledge, this is the first report of using an RNA-seq approach to study the host CNS response to persistent viral infection.",2013 Sep 18,"['Elliott, Ruth', 'Li, Fan', 'Dragomir, Isabelle', 'Chua, Ming Ming W.', 'Gregory, Brian D.', 'Weiss, Susan R.']",PLoS One,,,True
ede3bef01a48a154a93f1286b907cd5a53a086eb,PMC,Vesicular Transport of Progeny Parvovirus Particles through ER and Golgi Regulates Maturation and Cytolysis,http://dx.doi.org/10.1371/journal.ppat.1003605,PMC3777860,24068925,CC BY,"Progeny particles of non-enveloped lytic parvoviruses were previously shown to be actively transported to the cell periphery through vesicles in a gelsolin-dependent manner. This process involves rearrangement and destruction of actin filaments, while microtubules become protected throughout the infection. Here the focus is on the intracellular egress pathway, as well as its impact on the properties and release of progeny virions. By colocalization with cellular marker proteins and specific modulation of the pathways through over-expression of variant effector genes transduced by recombinant adeno-associated virus vectors, we show that progeny PV particles become engulfed into COPII-vesicles in the endoplasmic reticulum (ER) and are transported through the Golgi to the plasma membrane. Besides known factors like sar1, sec24, rab1, the ERM family proteins, radixin and moesin play (an) essential role(s) in the formation/loading and targeting of virus-containing COPII-vesicles. These proteins also contribute to the transport through ER and Golgi of the well described analogue of cellular proteins, the secreted Gaussia luciferase in absence of virus infection. It is therefore likely that radixin and moesin also serve for a more general function in cellular exocytosis. Finally, parvovirus egress via ER and Golgi appears to be necessary for virions to gain full infectivity through post-assembly modifications (e.g. phosphorylation). While not being absolutely required for cytolysis and progeny virus release, vesicular transport of parvoviruses through ER and Golgi significantly accelerates these processes pointing to a regulatory role of this transport pathway.",2013 Sep 19,"['Bär, Séverine', 'Rommelaere, Jean', 'Nüesch, Jürg P. F.']",PLoS Pathog,,,True
8f98c8621da6438169976931b2bc2cce12959a70,PMC,Rab-GDI Complex Dissociation Factor Expressed through Translational Frameshifting in Filamentous Ascomycetes,http://dx.doi.org/10.1371/journal.pone.0073772,PMC3777964,24069231,CC BY,"In the model fungus Podospora anserina, the PaYIP3 gene encoding the orthologue of the Saccharomyces cerevisiae YIP3 Rab-GDI complex dissociation factor expresses two polypeptides, one of which, the long form, is produced through a programmed translation frameshift. Inactivation of PaYIP3 results in slightly delayed growth associated with modification in repartition of fruiting body on the thallus, along with reduced ascospore production on wood. Long and short forms of PaYIP3 are expressed in the mycelium, while only the short form appears expressed in the maturing fruiting body (perithecium). The frameshift has been conserved over the evolution of the Pezizomycotina, lasting for over 400 million years, suggesting that it has an important role in the wild.",2013 Sep 19,"['Malagnac, Fabienne', 'Fabret, Céline', 'Prigent, Magali', 'Rousset, Jean-Pierre', 'Namy, Olivier', 'Silar, Philippe']",PLoS One,,,True
e54a9696e0da89388b8edef0dbe18a5f674a245b,PMC,"Virological Surveillance of Influenza Viruses during the 2008–09, 2009–10 and 2010–11 Seasons in Tunisia",http://dx.doi.org/10.1371/journal.pone.0074064,PMC3777972,24069267,CC BY,"BACKGROUND: The data contribute to a better understanding of the circulation of influenza viruses especially in North-Africa. OBJECTIVE: The objective of this surveillance was to detect severe influenza cases, identify their epidemiological and virological characteristics and assess their impact on the healthcare system. METHOD: We describe in this report the findings of laboratory-based surveillance of human cases of influenza virus and other respiratory viruses' infection during three seasons in Tunisia. RESULTS: The 2008–09 winter influenza season is underway in Tunisia, with co-circulation of influenza A/H3N2 (56.25%), influenza A(H1N1) (32.5%), and a few sporadic influenza B viruses (11.25%). In 2010–11 season the circulating strains are predominantly the 2009 pandemic influenza A(H1N1)pdm09 (70%) and influenza B viruses (22%). And sporadic viruses were sub-typed as A/H3N2 and unsubtyped influenza A, 5% and 3%, respectively. Unlike other countries, highest prevalence of influenza B virus Yamagata-like lineage has been reported in Tunisia (76%) localised into the clade B/Bangladesh/3333/2007. In the pandemic year, influenza A(H1N1)pdm09 predominated over other influenza viruses (95%). Amino acid changes D222G and D222E were detected in the HA gene of A(H1N1)pdm09 virus in two severe cases, one fatal case and one mild case out of 50 influenza A(H1N1)pdm09 viruses studied. The most frequently reported respiratory virus other than influenza in three seasons was RSV (45.29%). CONCLUSION: This article summarises the surveillance and epidemiology of influenza viruses and other respiratory viruses, showing how rapid improvements in influenza surveillance were feasible by connecting the existing structure in the health care system for patient records to electronic surveillance system for reporting ILI cases.",2013 Sep 19,"['El Moussi, Awatef', 'Pozo, Francisco', 'Ben Hadj Kacem, Mohamed Ali', 'Ledesma, Juan', 'Cuevas, Maria Teresa', 'Casas, Inmaculada', 'Slim, Amine']",PLoS One,,,True
f71d759c61dcef328233eb5cb93e7c5f101fa111,PMC,Acute phase response to Mycoplasma haemofelis and ‘Candidatus Mycoplasma haemominutum’ infection in FIV-infected and non-FIV-infected cats,http://dx.doi.org/10.1016/j.tvjl.2011.12.009,PMC3778745,22763129,CC BY,"The pathogenicity of Haemoplasma spp. in cats varies with ‘Candidatus Mycoplasma haemominutum’ (CMhm) causing subclinical infection while Mycoplasma haemofelis (Mhf) often induces haemolytic anaemia. The aims of this study were to characterise the acute phase response (APR) of the cat to experimental infection with Mhf or CMhm, and to determine whether chronic feline immunodeficiency virus (FIV) infection influences this response. The acute phase proteins serum amyloid A (SAA), haptoglobin (Hp) and α-1-acid glycoprotein (AGP) concentrations were measured pre-infection and every 7–14 days up to day 100 post-infection (pi) in cats infected with either Mhf or CMhm. Half of each group of cats (6/12) were chronically and subclinically infected with FIV. Marbofloxacin treatment was given on days 16–44 pi to half of the Mhf-infected cats, and on days 49–77 pi to half of the CMhm-infected cats. FIV-infected animals had significantly lower AGP concentrations, and significantly greater Hp concentrations than non-FIV-infected cats when infected with CMhm and Mhf, respectively. Both CMhm and Mhf infection were associated with significant increases in SAA concentrations, while AGP concentrations were only significantly increased by Mhf infection. Mhf-infected cats had significantly greater SAA concentrations than CMhm-infected animals. Both Mhf and CMhm infections were associated with an APR, with Mhf infection inducing a greater response. Chronic FIV infection appeared to modify the APR, which varied with the infecting Haemoplasma species.",2012 Aug,"['Korman, R.M.', 'Cerón, J.J.', 'Knowles, T.G.', 'Barker, E.N.', 'Eckersall, P.D.', 'Tasker, S.']",Vet J,,,False
f292a5fa02dc7ce9ea268920cc8657f4e34360f9,PMC,Different Mechanisms of Inflammation Induced in Virus and Autoimmune-Mediated Models of Multiple Sclerosis in C57BL6 Mice,http://dx.doi.org/10.1155/2013/589048,PMC3780522,24083230,CC BY,"Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system (CNS). Neurotropic demyelinating strain of MHV (MHV-A59 or its isogenic recombinant strain RSA59) induces MS-like disease in mice mediated by microglia, along with a small population of T cells. The mechanism of demyelination is at least in part due to microglia-mediated myelin stripping, with some direct axonal injury. Immunization with myelin oligodendrocyte glycoprotein (MOG) induces experimental autoimmune encephalomyelitis (EAE), a mainly CD4(+) T-cell-mediated disease, although CD8(+) T cells may play a significant role in demyelination. It is possible that both autoimmune and nonimmune mechanisms such as direct viral toxicity may induce MS. Our study directly compares CNS pathology in autoimmune and viral-induced MS models. Mice with viral-induced and EAE demyelinating diseases demonstrated similar patterns and distributions of demyelination that accumulated over the course of the disease. However, significant differences in acute inflammation were noted. Inflammation was restricted mainly to white matter at all times in EAE, whereas inflammation initially largely involved gray matter in acute MHV-induced disease and then is subsequently localized only in white matter in the chronic disease phase. The presence of dual mechanisms of demyelination may be responsible for the failure of immunosuppression to promote long-term remission in many MS patients.",2013 Aug 28,"['Kishore, Abhinoy', 'Kanaujia, Anurag', 'Nag, Soma', 'Rostami, A. M.', 'Kenyon, Lawrence C.', 'Shindler, Kenneth S.', 'Das Sarma, Jayasri']",Biomed Res Int,,,True
5b36690d168ab53e08482ce4b4b956d9ad3c1a10,PMC,Soluble Form of Canine Transferrin Receptor Inhibits Canine Parvovirus Infection In Vitro and In Vivo,http://dx.doi.org/10.1155/2013/172479,PMC3780538,24089666,CC BY,"Canine parvovirus (CPV) disease is an acute, highly infectious disease threatening the dog-raising industry. So far there are no effective therapeutic strategies to control this disease. Although the canine transferrin receptor (TfR) was identified as a receptor for CPV infection, whether extracellular domain of TfR (called soluble TfR (sTfR)) possesses anti-CPV activities remains elusive. Here, we used the recombinant sTfR prepared from HEK293T cells with codon-optimized gene structure to investigate its anti-CPV activity both in vitro and in vivo. Our results indicated that codon optimization could significantly improve sTfR expression in HEK293T cells. The prepared recombinant sTfR possessed a binding activity to both CPV and CPV VP2 capsid proteins and significantly inhibited CPV infection of cultured feline F81 cells and decreased the mortality of CPV-infected dogs, which indicates that the sTfR has the anti-CPV activity both in vitro and in vivo.",2013 Sep 8,"['Wen, Jiexia', 'Pan, Sumin', 'Liang, Shuang', 'Zhong, Zhenyu', 'He, Ying', 'Lin, Hongyu', 'Li, Wenyan', 'Wang, Liyue', 'Li, Xiujin', 'Zhong, Fei']",Biomed Res Int,,,True
3892a126c127795e96e4e071cf14fd7fdc2e4231,PMC,Inhibitory Effect of Matrine on Blood-Brain Barrier Disruption for the Treatment of Experimental Autoimmune Encephalomyelitis,http://dx.doi.org/10.1155/2013/736085,PMC3781841,24194630,CC BY,"Dysfunction of the blood-brain barrier (BBB) is a primary characteristic of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to suppress clinical EAE and CNS inflammation. However, whether this effect of MAT is through protecting the integrity and function of the BBB is not known. In the present study, we show that MAT treatment had a therapeutic effect comparable to dexamethasone (DEX) in EAE rats, with reduced Evans Blue extravasation, increased expression of collagen IV, the major component of the basement membrane, and the structure of tight junction (TJ) adaptor protein Zonula occludens-1 (ZO-1). Furthermore, MAT treatment attenuated expression of matrix metalloproteinase-9 and -2 (MMP-9/-2), while it increased the expression of tissue inhibitors of metalloproteinase-1 and -2 (TIMP-1/-2). Our findings demonstrate that MAT reduces BBB leakage by strengthening basement membrane, inhibiting activities of MMP-2 and -9, and upregulating their inhibitors. Taken together, our results identify a novel mechanism underlying the effect of MAT, a natural compound that could be a novel therapy for MS.",2013 Sep 8,"['Zhang, Su', 'Kan, Quan-Cheng', 'Xu, Yuming', 'Zhang, Guang-Xian', 'Zhu, Lin']",Mediators Inflamm,,,True
49f674332aef03ed0e231eaed321de8cb65b6644,PMC,"A Single Dose of Azithromycin Does Not Improve Clinical Outcomes of Children Hospitalised with Bronchiolitis: A Randomised, Placebo-Controlled Trial",http://dx.doi.org/10.1371/journal.pone.0074316,PMC3783434,24086334,CC BY,"OBJECTIVE: Bronchiolitis, one of the most common reasons for hospitalisation in young children, is particularly problematic in Indigenous children. Macrolides may be beneficial in settings where children have high rates of nasopharyngeal bacterial carriage and frequent prolonged illness. The aim of our double-blind placebo-controlled randomised trial was to determine if a large single dose of azithromycin (compared to placebo) reduced length of stay (LOS), duration of oxygen (O(2)) and respiratory readmissions within 6 months of children hospitalised with bronchiolitis. We also determined the effect of azithromycin on nasopharyngeal microbiology. METHODS: Children aged ≤18 months were randomised to receive a single large dose (30 mg/kg) of either azithromycin or placebo within 24 hrs of hospitalisation. Nasopharyngeal swabs were collected at baseline and 48hrs later. Primary endpoints (LOS, O(2)) were monitored every 12 hrs. Hospitalised respiratory readmissions 6-months post discharge was collected. RESULTS: 97 children were randomised (n = 50 azithromycin, n = 47 placebo). Median LOS was similar in both groups; azithromycin = 54 hours, placebo = 58 hours (difference between groups of 4 hours 95%CI -8, 13, p = 0.6). O(2) requirement was not significantly different between groups; Azithromycin = 35 hrs; placebo = 42 hrs (difference 7 hours, 95%CI -9, 13, p = 0.7). Number of children re-hospitalised was similar 10 per group (OR = 0.9, 95%CI 0.3, 2, p = 0.8). At least one virus was detected in 74% of children. The azithromycin group had reduced nasopharyngeal bacterial carriage (p = 0.01) but no difference in viral detection at 48 hours. CONCLUSION: Although a single dose of azithromycin reduces carriage of bacteria, it is unlikely to be beneficial in reducing LOS, duration of O(2) requirement or readmissions in children hospitalised with bronchiolitis. It remains uncertain if an earlier and/or longer duration of azithromycin improves clinical and microbiological outcomes for children. The trial was registered with the Australian and New Zealand Clinical Trials Register. Clinical trials number: ACTRN12608000150347. http://www.anzctr.org.au/TrialSearch.aspx.",2013 Sep 25,"['McCallum, Gabrielle B.', 'Morris, Peter S.', 'Chatfield, Mark D.', 'Maclennan, Carolyn', 'White, Andrew V.', 'Sloots, Theo P.', 'Mackay, Ian M.', 'Chang, Anne B.']",PLoS One,,,True
9caca240f207e4d98c2f98c7ec3818864afb8aeb,PMC,"A Single Dose of Azithromycin Does Not Improve Clinical Outcomes of Children Hospitalised with Bronchiolitis: A Randomised, Placebo-Controlled Trial",http://dx.doi.org/10.1371/journal.pone.0074316,PMC3783434,24086334,CC BY,"OBJECTIVE: Bronchiolitis, one of the most common reasons for hospitalisation in young children, is particularly problematic in Indigenous children. Macrolides may be beneficial in settings where children have high rates of nasopharyngeal bacterial carriage and frequent prolonged illness. The aim of our double-blind placebo-controlled randomised trial was to determine if a large single dose of azithromycin (compared to placebo) reduced length of stay (LOS), duration of oxygen (O(2)) and respiratory readmissions within 6 months of children hospitalised with bronchiolitis. We also determined the effect of azithromycin on nasopharyngeal microbiology. METHODS: Children aged ≤18 months were randomised to receive a single large dose (30 mg/kg) of either azithromycin or placebo within 24 hrs of hospitalisation. Nasopharyngeal swabs were collected at baseline and 48hrs later. Primary endpoints (LOS, O(2)) were monitored every 12 hrs. Hospitalised respiratory readmissions 6-months post discharge was collected. RESULTS: 97 children were randomised (n = 50 azithromycin, n = 47 placebo). Median LOS was similar in both groups; azithromycin = 54 hours, placebo = 58 hours (difference between groups of 4 hours 95%CI -8, 13, p = 0.6). O(2) requirement was not significantly different between groups; Azithromycin = 35 hrs; placebo = 42 hrs (difference 7 hours, 95%CI -9, 13, p = 0.7). Number of children re-hospitalised was similar 10 per group (OR = 0.9, 95%CI 0.3, 2, p = 0.8). At least one virus was detected in 74% of children. The azithromycin group had reduced nasopharyngeal bacterial carriage (p = 0.01) but no difference in viral detection at 48 hours. CONCLUSION: Although a single dose of azithromycin reduces carriage of bacteria, it is unlikely to be beneficial in reducing LOS, duration of O(2) requirement or readmissions in children hospitalised with bronchiolitis. It remains uncertain if an earlier and/or longer duration of azithromycin improves clinical and microbiological outcomes for children. The trial was registered with the Australian and New Zealand Clinical Trials Register. Clinical trials number: ACTRN12608000150347. http://www.anzctr.org.au/TrialSearch.aspx.",2013 Sep 25,"['McCallum, Gabrielle B.', 'Morris, Peter S.', 'Chatfield, Mark D.', 'Maclennan, Carolyn', 'White, Andrew V.', 'Sloots, Theo P.', 'Mackay, Ian M.', 'Chang, Anne B.']",PLoS One,,,False
fe5d9afd46890e2338d8d0febf8eaa8bd2166d60,PMC,"A Single Dose of Azithromycin Does Not Improve Clinical Outcomes of Children Hospitalised with Bronchiolitis: A Randomised, Placebo-Controlled Trial",http://dx.doi.org/10.1371/journal.pone.0074316,PMC3783434,24086334,CC BY,"OBJECTIVE: Bronchiolitis, one of the most common reasons for hospitalisation in young children, is particularly problematic in Indigenous children. Macrolides may be beneficial in settings where children have high rates of nasopharyngeal bacterial carriage and frequent prolonged illness. The aim of our double-blind placebo-controlled randomised trial was to determine if a large single dose of azithromycin (compared to placebo) reduced length of stay (LOS), duration of oxygen (O(2)) and respiratory readmissions within 6 months of children hospitalised with bronchiolitis. We also determined the effect of azithromycin on nasopharyngeal microbiology. METHODS: Children aged ≤18 months were randomised to receive a single large dose (30 mg/kg) of either azithromycin or placebo within 24 hrs of hospitalisation. Nasopharyngeal swabs were collected at baseline and 48hrs later. Primary endpoints (LOS, O(2)) were monitored every 12 hrs. Hospitalised respiratory readmissions 6-months post discharge was collected. RESULTS: 97 children were randomised (n = 50 azithromycin, n = 47 placebo). Median LOS was similar in both groups; azithromycin = 54 hours, placebo = 58 hours (difference between groups of 4 hours 95%CI -8, 13, p = 0.6). O(2) requirement was not significantly different between groups; Azithromycin = 35 hrs; placebo = 42 hrs (difference 7 hours, 95%CI -9, 13, p = 0.7). Number of children re-hospitalised was similar 10 per group (OR = 0.9, 95%CI 0.3, 2, p = 0.8). At least one virus was detected in 74% of children. The azithromycin group had reduced nasopharyngeal bacterial carriage (p = 0.01) but no difference in viral detection at 48 hours. CONCLUSION: Although a single dose of azithromycin reduces carriage of bacteria, it is unlikely to be beneficial in reducing LOS, duration of O(2) requirement or readmissions in children hospitalised with bronchiolitis. It remains uncertain if an earlier and/or longer duration of azithromycin improves clinical and microbiological outcomes for children. The trial was registered with the Australian and New Zealand Clinical Trials Register. Clinical trials number: ACTRN12608000150347. http://www.anzctr.org.au/TrialSearch.aspx.",2013 Sep 25,"['McCallum, Gabrielle B.', 'Morris, Peter S.', 'Chatfield, Mark D.', 'Maclennan, Carolyn', 'White, Andrew V.', 'Sloots, Theo P.', 'Mackay, Ian M.', 'Chang, Anne B.']",PLoS One,,,True
a462888bb4b9f31940fb166c07a8590406150575,PMC,Mucosal Vaccination with Recombinant Adenovirus Encoding Nucleoprotein Provides Potent Protection against Influenza Virus Infection,http://dx.doi.org/10.1371/journal.pone.0075460,PMC3783479,24086536,CC BY,"Influenza vaccines that target the highly variable surface glycoproteins hemagglutinin and neuraminidase cause inconvenience of having vaccination every year. For this reason, development of universal vaccines targeting conserved viral components is needed. In this study, we generated recombinant adenovirus (rAd) vaccine encoding nucleoprotein (NP) of A/PR/8/34 influenza virus, designated rAd/NP. BALB/c mice were immunized intranasally or sublingually with rAd/NP vaccine and subsequently challenged with lethal doses of heterologous as well as homologous influenza viruses. We found that intranasal immunization of rAd/NP elicited strong mucosal IgA responses as well as stronger CD8 T-cell responses toward immunodominant K(d)-restricted NP(147-155) epitope than sublingual immunization. Importantly, only single intranasal but not sublingual immunization of rAd/NP provides potent protection against both homologous and heterologous influenza virus challenges. These results suggest that recombinant rAd/NP could be a universal vaccine candidate for mucosal administration against influenza virus.",2013 Sep 25,"['Kim, So-Hee', 'Kim, Joo Young', 'Choi, Youngjoo', 'Nguyen, Huan H.', 'Song, Man Ki', 'Chang, Jun']",PLoS One,,,True
187062df058ff8a8110c008bc1f489986423ea1e,PMC,Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface,http://dx.doi.org/10.1371/journal.ppat.1003611,PMC3784481,24086132,CC BY,"Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases.",2013 Sep 26,"['Juranic Lisnic, Vanda', 'Babic Cac, Marina', 'Lisnic, Berislav', 'Trsan, Tihana', 'Mefferd, Adam', 'Das Mukhopadhyay, Chitrangada', 'Cook, Charles H.', 'Jonjic, Stipan', 'Trgovcich, Joanne']",PLoS Pathog,,,True
edd69dd68ae88e3aeb94be5c0f963806b86e6d65,PMC,Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface,http://dx.doi.org/10.1371/journal.ppat.1003611,PMC3784481,24086132,CC BY,"Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases.",2013 Sep 26,"['Juranic Lisnic, Vanda', 'Babic Cac, Marina', 'Lisnic, Berislav', 'Trsan, Tihana', 'Mefferd, Adam', 'Das Mukhopadhyay, Chitrangada', 'Cook, Charles H.', 'Jonjic, Stipan', 'Trgovcich, Joanne']",PLoS Pathog,,,False
54fc333fdf388bbf38305116d4971247a3681ca1,PMC,Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface,http://dx.doi.org/10.1371/journal.ppat.1003611,PMC3784481,24086132,CC BY,"Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases.",2013 Sep 26,"['Juranic Lisnic, Vanda', 'Babic Cac, Marina', 'Lisnic, Berislav', 'Trsan, Tihana', 'Mefferd, Adam', 'Das Mukhopadhyay, Chitrangada', 'Cook, Charles H.', 'Jonjic, Stipan', 'Trgovcich, Joanne']",PLoS Pathog,,,False
601a89290b86adc02519f8d826eb7499e1ed152e,PMC,Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface,http://dx.doi.org/10.1371/journal.ppat.1003611,PMC3784481,24086132,CC BY,"Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases.",2013 Sep 26,"['Juranic Lisnic, Vanda', 'Babic Cac, Marina', 'Lisnic, Berislav', 'Trsan, Tihana', 'Mefferd, Adam', 'Das Mukhopadhyay, Chitrangada', 'Cook, Charles H.', 'Jonjic, Stipan', 'Trgovcich, Joanne']",PLoS Pathog,,,False
b3490420de53f1b7bcaf510f6bcb562c1d6970c6,PMC,Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface,http://dx.doi.org/10.1371/journal.ppat.1003611,PMC3784481,24086132,CC BY,"Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases.",2013 Sep 26,"['Juranic Lisnic, Vanda', 'Babic Cac, Marina', 'Lisnic, Berislav', 'Trsan, Tihana', 'Mefferd, Adam', 'Das Mukhopadhyay, Chitrangada', 'Cook, Charles H.', 'Jonjic, Stipan', 'Trgovcich, Joanne']",PLoS Pathog,,,False
d766ab43735b3ae26606a19ef9ddbe46c77fb24e,PMC,Complete Genome Sequence of a Novel Feline Astrovirus from a Domestic Cat in Hong Kong,http://dx.doi.org/10.1128/genomeA.00708-13,PMC3784778,24072858,CC BY,"We report the first complete genome sequence of a feline astrovirus (FAstV), FAstV2 strain 1637F, identified from a domestic cat. The genome is 6,779 nucleotides (nt) in length and consists of three overlapping open reading frames (ORF1a-ORF1b-ORF2). Sequence analysis suggests that FAstV2 represents a new FAstV genotype that is closely related to human astroviruses.",2013 Sep 26,"['Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Yip, Cyril C. Y.', 'Bai, Ru', 'Wu, Ying', 'Tse, Herman', 'Yuen, Kwok-yung']",Genome Announc,,,True
338d45deb88de8cc7f4cf5158c4752fb3533a0b7,PMC,Development of a New Resequencing Pathogen Microarray Based Assay for Detection of Broad-Spectrum Respiratory Tract Viruses in Patients with Community-Acquired Pneumonia,http://dx.doi.org/10.1371/journal.pone.0075704,PMC3785410,24086618,CC BY,"A Resequencing Pathogen Microarray (RPM) is a single, highly multiplexed assay for detecting and differentiating similarly related pathogens by using closely overlapping probe sets to determine a target organism’s nucleotide sequence. In this study, a new RPM (RPM-IVDC1) that consisted of 224-bp detector tiles corresponding to 9 influenza A subtypes, 11 rhinoviruses, 28 enteroviruses and 38 other respiratory viruses was developed and optimized to provide individual and simultaneous detection sensitivities ranging from 15 to 750 genomic copies for 16 common respiratory pathogens. A total of 110 consecutive patients with community-acquired pneumonia (CAP) admitted to 5 district general hospitals in Beijing during a 1-year period were assessed using the new assay. Among the children (under age 5) and adult patients (above age 18), respiratory syncytial virus (RSV) and rhinovirus (RV) were the most common etiological agents, respectively, which is consistent with reference assays. Atypical pathogens that may cause CAP-like illness, including rubella virus, measles virus, influenza type C virus, human herpesvirus (HHV) were also detected. The results show the capability of RPM-IVDC1 for the accurate detection and identification of multiple virus types, which may be of significant use in epidemic surveillance and outbreak investigations of atypical pathogens.",2013 Sep 27,"['Shen, Hongwei', 'Shi, Weixian', 'Wang, Ji', 'Wang, Miao', 'Li, Jin', 'Zhang, Chen', 'Nie, Kai', 'Yang, Mengjie', 'Zhang, Yi', 'Li, Aihua', 'Tan, Wenjie', 'Ma, Xuejun']",PLoS One,,,True
55b7d9b5320f9763edab4a3d32586bbf5dc2c487,PMC,The Potential of Metatranscriptomics for Identifying Screening Targets for Bacterial Vaginosis,http://dx.doi.org/10.1371/journal.pone.0076892,PMC3785445,24086764,CC BY,"BACKGROUND: The ribosomal RNA content of a sample collected from a woman with bacterial vaginosis (BV) was analysed to determine the active microbial community, and to identify potential targets for further screening. METHODOLOGY/PRINCIPAL FINDINGS: The sample from the BV patient underwent total RNA extraction, followed by physical subtraction of human rRNA and whole transcriptome amplification. The metatranscriptome was sequenced using Roche 454 titanium chemistry. The bioinformatics pipeline MG-RAST and desktop DNA analysis platforms were utilised to analyse results. Bacteria of the genus Prevotella (predominately P. amnii) constituted 36% of the 16S rRNA reads, followed by Megasphaera (19%), Leptotrichia/Sneathia (8%) and Fusobacterium (8%). Comparison of the abundances of several bacteria to quantitative PCR (qPCR) screening of extracted DNA revealed comparable relative abundances. This suggests a correlation between what was present and transcriptionally active in this sample: however distinct differences were seen when compared to the microbiome determined by 16S rRNA gene amplicon sequencing. To assess the presence of P. amnii in a larger pool of samples, 90 sexually active women were screened using qPCR. This bacterium was found to be strongly associated with BV (P<0.001, OR 23.3 (95%CI:2.9–190.7)) among the 90 women. CONCLUSIONS/SIGNIFICANCE: This study highlighted the potential of metatranscriptomics as a tool for characterising metabolically active microbiota and identifying targets for further screening. Prevotella amnii was chosen as an example target, being the most metabolically active species present in the single patient with BV, and was found to be detected at a high concentration by qPCR in 31% of cohort with BV, with an association with both oral and penile-vaginal sex.",2013 Sep 27,"['Twin, Jimmy', 'Bradshaw, Catriona S.', 'Garland, Suzanne M.', 'Fairley, Christopher K.', 'Fethers, Katherine', 'Tabrizi, Sepehr N.']",PLoS One,,,True
f56c5a350cc09b29ab51068039bfb27523945e09,PMC,Spatiotemporal Infectious Disease Modeling: A BME-SIR Approach,http://dx.doi.org/10.1371/journal.pone.0072168,PMC3785461,24086257,CC BY,"This paper is concerned with the modeling of infectious disease spread in a composite space-time domain under conditions of uncertainty. We focus on stochastic modeling that accounts for basic mechanisms of disease distribution and multi-sourced in situ uncertainties. Starting from the general formulation of population migration dynamics and the specification of transmission and recovery rates, the model studies the functional formulation of the evolution of the fractions of susceptible-infected-recovered individuals. The suggested approach is capable of: a) modeling population dynamics within and across localities, b) integrating the disease representation (i.e. susceptible-infected-recovered individuals) with observation time series at different geographical locations and other sources of information (e.g. hard and soft data, empirical relationships, secondary information), and c) generating predictions of disease spread and associated parameters in real time, while considering model and observation uncertainties. Key aspects of the proposed approach are illustrated by means of simulations (i.e. synthetic studies), and a real-world application using hand-foot-mouth disease (HFMD) data from China.",2013 Sep 27,"['Angulo, Jose', 'Yu, Hwa-Lung', 'Langousis, Andrea', 'Kolovos, Alexander', 'Wang, Jinfeng', 'Madrid, Ana Esther', 'Christakos, George']",PLoS One,,,True
74007d5a0dcfc70e0dbd281081f1408fed1a9116,PMC,Scoping Review on Search Queries and Social Media for Disease Surveillance: A Chronology of Innovation,http://dx.doi.org/10.2196/jmir.2740,PMC3785982,23896182,CC BY,"BACKGROUND: The threat of a global pandemic posed by outbreaks of influenza H5N1 (1997) and Severe Acute Respiratory Syndrome (SARS, 2002), both diseases of zoonotic origin, provoked interest in improving early warning systems and reinforced the need for combining data from different sources. It led to the use of search query data from search engines such as Google and Yahoo! as an indicator of when and where influenza was occurring. This methodology has subsequently been extended to other diseases and has led to experimentation with new types of social media for disease surveillance. OBJECTIVE: The objective of this scoping review was to formally assess the current state of knowledge regarding the use of search queries and social media for disease surveillance in order to inform future work on early detection and more effective mitigation of the effects of foodborne illness. METHODS: Structured scoping review methods were used to identify, characterize, and evaluate all published primary research, expert review, and commentary articles regarding the use of social media in surveillance of infectious diseases from 2002-2011. RESULTS: Thirty-two primary research articles and 19 reviews and case studies were identified as relevant. Most relevant citations were peer-reviewed journal articles (29/32, 91%) published in 2010-11 (28/32, 88%) and reported use of a Google program for surveillance of influenza. Only four primary research articles investigated social media in the context of foodborne disease or gastroenteritis. Most authors (21/32 articles, 66%) reported that social media-based surveillance had comparable performance when compared to an existing surveillance program. The most commonly reported strengths of social media surveillance programs included their effectiveness (21/32, 66%) and rapid detection of disease (21/32, 66%). The most commonly reported weaknesses were the potential for false positive (16/32, 50%) and false negative (11/32, 34%) results. Most authors (24/32, 75%) recommended that social media programs should primarily be used to support existing surveillance programs. CONCLUSIONS: The use of search queries and social media for disease surveillance are relatively recent phenomena (first reported in 2006). Both the tools themselves and the methodologies for exploiting them are evolving over time. While their accuracy, speed, and cost compare favorably with existing surveillance systems, the primary challenge is to refine the data signal by reducing surrounding noise. Further developments in digital disease surveillance have the potential to improve sensitivity and specificity, passively through advances in machine learning and actively through engagement of users. Adoption, even as supporting systems for existing surveillance, will entail a high level of familiarity with the tools and collaboration across jurisdictions.",2013 Jul 18,"['Bernardo, Theresa Marie', 'Rajic, Andrijana', 'Young, Ian', 'Robiadek, Katie', 'Pham, Mai T', 'Funk, Julie A']",J Med Internet Res,,,False
8f9f22f0d245cf41e5047230fa1c907b47a734ac,PMC,Virus-induced exacerbations in asthma and COPD,http://dx.doi.org/10.3389/fmicb.2013.00293,PMC3787546,24098299,CC BY,"Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation and/or airflow limitation due to pulmonary emphysema. Chronic bronchitis, pulmonary emphysema, and bronchial asthma may all be associated with airflow limitation; therefore, exacerbation of asthma may be associated with the pathophysiology of COPD. Furthermore, recent studies have suggested that the exacerbation of asthma, namely virus-induced asthma, may be associated with a wide variety of respiratory viruses. COPD and asthma have different underlying pathophysiological processes and thus require individual therapies. Exacerbation of both COPD and asthma, which are basically defined and diagnosed by clinical symptoms, is associated with a rapid decline in lung function and increased mortality. Similar pathogens, including human rhinovirus, respiratory syncytial virus, influenza virus, parainfluenza virus, and coronavirus, are also frequently detected during exacerbation of asthma and/or COPD. Immune response to respiratory viral infections, which may be related to the severity of exacerbation in each disease, varies in patients with both COPD and asthma. In this regard, it is crucial to recognize and understand both the similarities and differences of clinical features in patients with COPD and/or asthma associated with respiratory viral infections, especially in the exacerbative stage. In relation to definition, epidemiology, and pathophysiology, this review aims to summarize current knowledge concerning exacerbation of both COPD and asthma by focusing on the clinical significance of associated respiratory virus infections.",2013 Oct 1,"['Kurai, Daisuke', 'Saraya, Takeshi', 'Ishii, Haruyuki', 'Takizawa, Hajime']",Front Microbiol,,,True
274eab479084dcb79951d6fdde012c9eab9bb469,PMC,Ligand Pose and Orientational Sampling in Molecular Docking,http://dx.doi.org/10.1371/journal.pone.0075992,PMC3787967,24098414,CC BY,"Molecular docking remains an important tool for structure-based screening to find new ligands and chemical probes. As docking ambitions grow to include new scoring function terms, and to address ever more targets, the reliability and extendability of the orientation sampling, and the throughput of the method, become pressing. Here we explore sampling techniques that eliminate stochastic behavior in DOCK3.6, allowing us to optimize the method for regularly variable sampling of orientations. This also enabled a focused effort to optimize the code for efficiency, with a three-fold increase in the speed of the program. This, in turn, facilitated extensive testing of the method on the 102 targets, 22,805 ligands and 1,411,214 decoys of the Directory of Useful Decoys - Enhanced (DUD-E) benchmarking set, at multiple levels of sampling. Encouragingly, we observe that as sampling increases from 50 to 500 to 2000 to 5000 to 20000 molecular orientations in the binding site (and so from about 1×10(10) to 4×10(10) to 1×10(11) to 2×10(11) to 5×10(11) mean atoms scored per target, since multiple conformations are sampled per orientation), the enrichment of ligands over decoys monotonically increases for most DUD-E targets. Meanwhile, including internal electrostatics in the evaluation ligand conformational energies, and restricting aromatic hydroxyls to low energy rotamers, further improved enrichment values. Several of the strategies used here to improve the efficiency of the code are broadly applicable in the field.",2013 Oct 1,"['Coleman, Ryan G.', 'Carchia, Michael', 'Sterling, Teague', 'Irwin, John J.', 'Shoichet, Brian K.']",PLoS One,,,True
33b590b2a517896a894c71c1c0b86c593804c034,PMC,"Use of a Safe, Reproducible, and Rapid Aerosol Delivery Method to Study Infection by Burkholderia pseudomallei and Burkholderia mallei in Mice",http://dx.doi.org/10.1371/journal.pone.0076804,PMC3788738,24098563,CC BY,"Burkholderia pseudomallei, the etiologic agent of melioidosis, is a saprophytic bacterium readily isolated from wet soils of countries bordering the equator. Burkholderia mallei is a host-adapted clone of B. pseudomallei that does not persist outside of its equine reservoir and causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by these organisms typically occurs via percutaneous inoculation or inhalation of aerosols, and the most common manifestation is severe pneumonia leading to fatal bacteremia. Glanders and melioidosis are difficult to diagnose and require prolonged antibiotic therapy with low success rates. There are no vaccines available to protect against either Burkholderia species, and there is concern regarding their use as biological warfare agents given that B. mallei has previously been utilized in this manner. Hence, experiments were performed to establish a mouse model of aerosol infection to study the organisms and develop countermeasures. Using a hand-held aerosolizer, BALB/c mice were inoculated intratracheally with strains B. pseudomallei 1026b and B. mallei ATCC23344 and growth of the agents in the lungs, as well as dissemination to the spleen, were examined. Mice infected with 10(2), 10(3) and 10(4) organisms were unable to control growth of B. mallei in the lungs and bacteria rapidly disseminated to the spleen. Though similar results were observed in mice inoculated with 10(3) and 10(4) B. pseudomallei cells, animals infected with 10(2) organisms controlled bacterial replication in the lungs, dissemination to the spleen, and the extent of bacteremia. Analysis of sera from mice surviving acute infection revealed that animals produced antibodies against antigens known to be targets of the immune response in humans. Taken together, these data show that small volume aerosol inoculation of mice results in acute disease, dose-dependent chronic infection, and immune responses that correlate with those seen in human infections.",2013 Oct 2,"['Lafontaine, Eric R.', 'Zimmerman, Shawn M.', 'Shaffer, Teresa L.', 'Michel, Frank', 'Gao, Xiudan', 'Hogan, Robert J.']",PLoS One,,,True
efba2008a6ccf1ad2614aebd79a6a741ea6538b9,PMC,Immunomodulatory Activity and Protective Effects of Polysaccharide from Eupatorium adenophorum Leaf Extract on Highly Pathogenic H5N1 Influenza Infection,http://dx.doi.org/10.1155/2013/194976,PMC3789439,24159339,CC BY,"The development of novel broad-spectrum, antiviral agents against H5N1 infection is urgently needed. In this study, we evaluated the immunomodulatory activities and protective effect of Eupatorium adenophorum polysaccharide (EAP) against the highly pathogenic H5N1 subtype influenza virus. EAP treatment significantly increased the production of IL-6, TNF-α, and IFN-γ both in vivo and in vitro as measured by qPCR and ELISA. In a mouse infection model, intranasal administration of EAP at a dose of 25 mg/kg body weight prior to H5N1 viral challenge efficiently inhibited viral replication, decreased lung lesions, and increased survival rate. We further evaluated the innate immune recognition of EAP, as this process is regulated primarily Dectin-1 and mannose receptor (MR). These results indicate that EAP may have immunomodulatory properties and a potential prophylactic effect against H5N1 influenza infection. Our investigation suggests an alternative strategy for the development of novel antiinfluenza agents and benefits of E. adenophorum products.",2013 Sep 18,"['Jin, Yi', 'Zhang, Yuewei', 'Wan, Chunyan', 'Wang, Hongjun', 'Hou, Lingyu', 'Chang, Jianyu', 'Fan, Kai', 'Xie, Xiangming']",Evid Based Complement Alternat Med,,,True
5c533a06c3dc5afefab5dd138ec4de394b537261,PMC,Role of the Spike Glycoprotein of Human Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Virus Entry and Syncytia Formation,http://dx.doi.org/10.1371/journal.pone.0076469,PMC3789674,24098509,CC BY,"Little is known about the biology of the emerging human group c betacoronavirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV). Because coronavirus spike glycoproteins (S) mediate virus entry, affect viral host range, and elicit neutralizing antibodies, analyzing the functions of MERS-CoV S protein is a high research priority. MERS-CoV S on lentivirus pseudovirions mediated entry into a variety of cell types including embryo cells from New World Eptesicus fuscus bats. Surprisingly, a polyclonal antibody to the S protein of MHV, a group a murine betacoronavirus, cross-reacted in immunoblots with the S2 domain of group c MERS-CoV spike protein. MERS pseudovirions released from 293T cells contained only uncleaved S, and pseudovirus entry was blocked by lysosomotropic reagents NH(4)Cl and bafilomycin and inhibitors of cathepsin L. However, when MERS pseudovirions with uncleaved S protein were adsorbed at 4°C to Vero E6 cells, brief trypsin treatment at neutral pH triggered virus entry at the plasma membrane and syncytia formation. When 293T cells producing MERS pseudotypes co-expressed serine proteases TMPRSS-2 or -4, large syncytia formed at neutral pH, and the pseudovirions produced were non-infectious and deficient in S protein. These experiments show that if S protein on MERS pseudovirions is uncleaved, then viruses enter by endocytosis in a cathepsin L-dependent manner, but if MERS-CoV S is cleaved, either during virus maturation by serine proteases or on pseudovirions by trypsin in extracellular fluids, then viruses enter at the plasma membrane at neutral pH and cause massive syncytia formation even in cells that express little or no MERS-CoV receptor. Thus, whether MERS-CoV enters cells within endosomes or at the plasma membrane depends upon the host cell type and tissue, and is determined by the location of host proteases that cleave the viral spike glycoprotein and activate membrane fusion.",2013 Oct 3,"['Qian, Zhaohui', 'Dominguez, Samuel R.', 'Holmes, Kathryn V.']",PLoS One,,,True
a6fc1b376a385d9f49f852a9f53e1e9149cb556a,PMC,Sequestration by IFIT1 Impairs Translation of 2′O-unmethylated Capped RNA,http://dx.doi.org/10.1371/journal.ppat.1003663,PMC3789756,24098121,CC BY,"Viruses that generate capped RNA lacking 2′O methylation on the first ribose are severely affected by the antiviral activity of Type I interferons. We used proteome-wide affinity purification coupled to mass spectrometry to identify human and mouse proteins specifically binding to capped RNA with different methylation states. This analysis, complemented with functional validation experiments, revealed that IFIT1 is the sole interferon-induced protein displaying higher affinity for unmethylated than for methylated capped RNA. IFIT1 tethers a species-specific protein complex consisting of other IFITs to RNA. Pulsed stable isotope labelling with amino acids in cell culture coupled to mass spectrometry as well as in vitro competition assays indicate that IFIT1 sequesters 2′O-unmethylated capped RNA and thereby impairs binding of eukaryotic translation initiation factors to 2′O-unmethylated RNA template, which results in inhibition of translation. The specificity of IFIT1 for 2′O-unmethylated RNA serves as potent antiviral mechanism against viruses lacking 2′O-methyltransferase activity and at the same time allows unperturbed progression of the antiviral program in infected cells.",2013 Oct 3,"['Habjan, Matthias', 'Hubel, Philipp', 'Lacerda, Livia', 'Benda, Christian', 'Holze, Cathleen', 'Eberl, Christian H.', 'Mann, Angelika', 'Kindler, Eveline', 'Gil-Cruz, Cristina', 'Ziebuhr, John', 'Thiel, Volker', 'Pichlmair, Andreas']",PLoS Pathog,,,True
a5cd1a73534959eff5332bcd3e5bc012f38c9137,PMC,Sensitive Detection of Viral Transcripts in Human Tumor Transcriptomes,http://dx.doi.org/10.1371/journal.pcbi.1003228,PMC3789765,24098097,CC BY,"In excess of [Image: see text]% of human cancer incidents have a viral cofactor. Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered. Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcripts. However, technical problems such as low abundances of viral transcripts in large volumes of sequencing data, viral sequence divergence, and homology between viral and human factors significantly confound identification of tumor viruses. We have developed a novel computational approach for detecting viral transcripts in human cancers that takes the aforementioned confounding factors into account and is applicable to a wide variety of viruses and tumors. We apply the approach to conducting the first systematic search for viruses in neuroblastoma, the most common cancer in infancy. The diverse clinical progression of this disease as well as related epidemiological and virological findings are highly suggestive of a pathogenic cofactor. However, a viral etiology of neuroblastoma is currently contested. We mapped [Image: see text] transcriptomes of neuroblastoma as well as positive and negative controls to the human and all known viral genomes in order to detect both known and unknown viruses. Analysis of controls, comparisons with related methods, and statistical estimates demonstrate the high sensitivity of our approach. Detailed investigation of putative viral transcripts within neuroblastoma samples did not provide evidence for the existence of any known human viruses. Likewise, de-novo assembly and analysis of chimeric transcripts did not result in expression signatures associated with novel human pathogens. While confounding factors such as sample dilution or viral clearance in progressed tumors may mask viral cofactors in the data, in principle, this is rendered less likely by the high sensitivity of our approach and the number of biological replicates analyzed. Therefore, our results suggest that frequent viral cofactors of metastatic neuroblastoma are unlikely.",2013 Oct 3,"['Schelhorn, Sven-Eric', 'Fischer, Matthias', 'Tolosi, Laura', 'Altmüller, Janine', 'Nürnberg, Peter', 'Pfister, Herbert', 'Lengauer, Thomas', 'Berthold, Frank']",PLoS Comput Biol,,,True
cabe96ceeaf4de3ad158c2579936a1ff3dfa352d,PMC,Ligand Clouds around Protein Clouds: A Scenario of Ligand Binding with Intrinsically Disordered Proteins,http://dx.doi.org/10.1371/journal.pcbi.1003249,PMC3789766,24098099,CC BY,"Intrinsically disordered proteins (IDPs) were found to be widely associated with human diseases and may serve as potential drug design targets. However, drug design targeting IDPs is still in the very early stages. Progress in drug design is usually achieved using experimental screening; however, the structural disorder of IDPs makes it difficult to characterize their interaction with ligands using experiments alone. To better understand the structure of IDPs and their interactions with small molecule ligands, we performed extensive simulations on the c-Myc(370–409) peptide and its binding to a reported small molecule inhibitor, ligand 10074-A4. We found that the conformational space of the apo c-Myc(370–409) peptide was rather dispersed and that the conformations of the peptide were stabilized mainly by charge interactions and hydrogen bonds. Under the binding of the ligand, c-Myc(370–409) remained disordered. The ligand was found to bind to c-Myc(370–409) at different sites along the chain and behaved like a ‘ligand cloud’. In contrast to ligand binding to more rigid target proteins that usually results in a dominant bound structure, ligand binding to IDPs may better be described as ligand clouds around protein clouds. Nevertheless, the binding of the ligand and a non-ligand to the c-Myc(370–409) target could be clearly distinguished. The present study provides insights that will help improve rational drug design that targets IDPs.",2013 Oct 3,"['Jin, Fan', 'Yu, Chen', 'Lai, Luhua', 'Liu, Zhirong']",PLoS Comput Biol,,,True
a49651276ae7cd5bf402c1066944fb7cfc83ffaa,PMC,Contribution of Host Intracellular Transport Machineries to Intercellular Movement of Turnip Mosaic Virus,http://dx.doi.org/10.1371/journal.ppat.1003683,PMC3789768,24098128,CC BY,"The contribution of different host cell transport systems in the intercellular movement of turnip mosaic virus (TuMV) was investigated. To discriminate between primary infections and secondary infections associated with the virus intercellular movement, a gene cassette expressing GFP-HDEL was inserted adjacent to a TuMV infectious cassette expressing 6K(2):mCherry, both within the T-DNA borders of the binary vector pCambia. In this system, both gene cassettes were delivered to the same cell by a single binary vector and primary infection foci emitted green and red fluorescence while secondarily infected cells emitted only red fluorescence. Intercellular movement was measured at 72 hours post infiltration and was estimated to proceed at an average rate of one cell being infected every three hours over an observation period of 17 hours. To determine if the secretory pathway were important for TuMV intercellular movement, chemical and protein inhibitors that blocked both early and late secretory pathways were used. Treatment with Brefeldin A or Concanamycin A or expression of ARF1 or RAB-E1d dominant negative mutants, all of which inhibit pre- or post-Golgi transport, reduced intercellular movement by the virus. These treatments, however, did not inhibit virus replication in primary infected cells. Pharmacological interference assays using Tyrphostin A23 or Wortmannin showed that endocytosis was not important for TuMV intercellular movement. Lack of co-localization by endocytosed FM4-64 and Ara7 (AtRabF2b) with TuMV-induced 6K(2)-tagged vesicles further supported this conclusion. Microfilament depolymerizing drugs and silencing expression of myosin XI-2 gene, but not myosin VIII genes, also inhibited TuMV intercellular movement. Expression of dominant negative myosin mutants confirmed the role played by myosin XI-2 as well as by myosin XI-K in TuMV intercellular movement. Using this dual gene cassette expression system and transport inhibitors, components of the secretory and actomyosin machinery were shown to be important for TuMV intercellular spread.",2013 Oct 3,"['Agbeci, Maxime', 'Grangeon, Romain', 'Nelson, Richard S.', 'Zheng, Huanquan', 'Laliberté, Jean-François']",PLoS Pathog,,,True
9c35a7f4d301162bfc79c1d7174a234ab94c2c46,PMC,Effect of the Plasmid-DNA Vaccination on Macroscopic and Microscopic Damage Caused by the Experimental Chronic Trypanosoma cruzi Infection in the Canine Model,http://dx.doi.org/10.1155/2013/826570,PMC3791577,24163822,CC BY,"The dog is considered the main domestic reservoir for Trypanosoma cruzi infection and a suitable experimental animal model to study the pathological changes during the course of Chagas disease (CD). Vaccine development is one of CD prevention methods to protect people at risk. Two plasmids containing genes encoding a trans-sialidase protein (TcSP) and an amastigote-specific glycoprotein (TcSSP4) were used as DNA vaccines in a canine model. Splenomegaly was not found in either of the recombinant plasmid-immunized groups; however, cardiomegaly was absent in animals immunized only with the plasmid containing the TcSSP4 gene. The inflammation of subendocardial and myocardial tissues was prevented only with the immunization with TcSSP4 gene. In conclusion, the vaccination with these genes has a partial protective effect on the enlargement of splenic and cardiac tissues during the chronic CD and on microscopic hearth damage, since both plasmids prevented splenomegaly but only one avoided cardiomegaly, and the lesions in heart tissue of dog immunized with plasmid containing the TcSSP4 gene covered only subepicardial tissue.",2013 Sep 19,"['Rodríguez-Morales, Olivia', 'Carrillo-Sánchez, Silvia C.', 'García-Mendoza, Humberto', 'Aranda-Fraustro, Alberto', 'Ballinas-Verdugo, Martha A.', 'Alejandre-Aguilar, Ricardo', 'Rosales-Encina, José Luis', 'Vallejo, Maite', 'Arce-Fonseca, Minerva']",Biomed Res Int,,,True
ca46ca49c4bf5dd684e066f5674cc980b7afb0a5,PMC,Comparative Serological Assays for the Study of H5 and H7 Avian Influenza Viruses,http://dx.doi.org/10.1155/2013/286158,PMC3791816,24163763,CC BY,"The nature of influenza virus to randomly mutate and evolve into new types is an important challenge in the control of influenza infection. It is necessary to monitor virus evolution for a better understanding of the pandemic risk posed by certain variants as evidenced by the highly pathogenic avian influenza (HPAI) viruses. This has been clearly recognized in Egypt following the notification of the first HPAI H5N1 outbreak. The continuous circulation of the virus and the mass vaccination programme undertaken in poultry have resulted in a progressive genetic evolution and a significant antigenic drift near the major antigenic sites. In order to establish if vaccination is sufficient to provide significant intra- and interclade cross-protection, lentiviral pseudotypes derived from H5N1 HPAI viruses (A/Vietnam/1194/04, A/chicken/Egypt-1709-01/2007) and an antigenic drift variant (A/chicken/Egypt-1709-06-2008) were constructed and used in pseudotype-based neutralization assays (pp-NT). pp-NT data obtained was confirmed and correlated with HI and MN assays. A panel of pseudotypes belonging to influenza Groups 1 and 2, with a combination of reporter systems, was also employed for testing avian sera in order to support further application of pp-NT as an alternative valid assay that can improve avian vaccination efficacy testing, vaccine virus selection, and the reliability of reference sera.",2013 Sep 15,"['Molesti, Eleonora', 'Milani, Adelaide', 'Terregino, Calogero', 'Cattoli, Giovanni', 'Temperton, Nigel J.']",Influenza Res Treat,,,True
e0c998049a9e7640184eeee597c13d35a43ccfef,PMC,iSNO-AAPair: incorporating amino acid pairwise coupling into PseAAC for predicting cysteine S-nitrosylation sites in proteins,http://dx.doi.org/10.7717/peerj.171,PMC3792191,24109555,CC BY,"As one of the most important and universal posttranslational modifications (PTMs) of proteins, S-nitrosylation (SNO) plays crucial roles in a variety of biological processes, including the regulation of cellular dynamics and many signaling events. Knowledge of SNO sites in proteins is very useful for drug development and basic research as well. Unfortunately, it is both time-consuming and costly to determine the SNO sites purely based on biological experiments. Facing the explosive protein sequence data generated in the post-genomic era, we are challenged to develop automated vehicles for timely and effectively determining the SNO sites for uncharacterized proteins. To address the challenge, a new predictor called iSNO-AAPair was developed by taking into account the coupling effects for all the pairs formed by the nearest residues and the pairs by the next nearest residues along protein chains. The cross-validation results on a state-of-the-art benchmark have shown that the new predictor outperformed the existing predictors. The same was true when tested by the independent proteins whose experimental SNO sites were known. A user-friendly web-server for iSNO-AAPair was established at http://app.aporc.org/iSNO-AAPair/, by which users can easily obtain their desired results without the need to follow the mathematical equations involved during its development.",2013 Oct 3,"['Xu, Yan', 'Shao, Xiao-Jian', 'Wu, Ling-Yun', 'Deng, Nai-Yang', 'Chou, Kuo-Chen']",PeerJ,,,False
a45bf1e6e622e9e69cc38fc265e2cf4d75bf51a4,PMC,iSNO-AAPair: incorporating amino acid pairwise coupling into PseAAC for predicting cysteine S-nitrosylation sites in proteins,http://dx.doi.org/10.7717/peerj.171,PMC3792191,24109555,CC BY,"As one of the most important and universal posttranslational modifications (PTMs) of proteins, S-nitrosylation (SNO) plays crucial roles in a variety of biological processes, including the regulation of cellular dynamics and many signaling events. Knowledge of SNO sites in proteins is very useful for drug development and basic research as well. Unfortunately, it is both time-consuming and costly to determine the SNO sites purely based on biological experiments. Facing the explosive protein sequence data generated in the post-genomic era, we are challenged to develop automated vehicles for timely and effectively determining the SNO sites for uncharacterized proteins. To address the challenge, a new predictor called iSNO-AAPair was developed by taking into account the coupling effects for all the pairs formed by the nearest residues and the pairs by the next nearest residues along protein chains. The cross-validation results on a state-of-the-art benchmark have shown that the new predictor outperformed the existing predictors. The same was true when tested by the independent proteins whose experimental SNO sites were known. A user-friendly web-server for iSNO-AAPair was established at http://app.aporc.org/iSNO-AAPair/, by which users can easily obtain their desired results without the need to follow the mathematical equations involved during its development.",2013 Oct 3,"['Xu, Yan', 'Shao, Xiao-Jian', 'Wu, Ling-Yun', 'Deng, Nai-Yang', 'Chou, Kuo-Chen']",PeerJ,,,False
951d9485254b93d47b0f2de99c4437966f1f202b,PMC,iSNO-AAPair: incorporating amino acid pairwise coupling into PseAAC for predicting cysteine S-nitrosylation sites in proteins,http://dx.doi.org/10.7717/peerj.171,PMC3792191,24109555,CC BY,"As one of the most important and universal posttranslational modifications (PTMs) of proteins, S-nitrosylation (SNO) plays crucial roles in a variety of biological processes, including the regulation of cellular dynamics and many signaling events. Knowledge of SNO sites in proteins is very useful for drug development and basic research as well. Unfortunately, it is both time-consuming and costly to determine the SNO sites purely based on biological experiments. Facing the explosive protein sequence data generated in the post-genomic era, we are challenged to develop automated vehicles for timely and effectively determining the SNO sites for uncharacterized proteins. To address the challenge, a new predictor called iSNO-AAPair was developed by taking into account the coupling effects for all the pairs formed by the nearest residues and the pairs by the next nearest residues along protein chains. The cross-validation results on a state-of-the-art benchmark have shown that the new predictor outperformed the existing predictors. The same was true when tested by the independent proteins whose experimental SNO sites were known. A user-friendly web-server for iSNO-AAPair was established at http://app.aporc.org/iSNO-AAPair/, by which users can easily obtain their desired results without the need to follow the mathematical equations involved during its development.",2013 Oct 3,"['Xu, Yan', 'Shao, Xiao-Jian', 'Wu, Ling-Yun', 'Deng, Nai-Yang', 'Chou, Kuo-Chen']",PeerJ,,,False
7de170f92a16c989329781224d8616189e55d598,PMC,iSNO-AAPair: incorporating amino acid pairwise coupling into PseAAC for predicting cysteine S-nitrosylation sites in proteins,http://dx.doi.org/10.7717/peerj.171,PMC3792191,24109555,CC BY,"As one of the most important and universal posttranslational modifications (PTMs) of proteins, S-nitrosylation (SNO) plays crucial roles in a variety of biological processes, including the regulation of cellular dynamics and many signaling events. Knowledge of SNO sites in proteins is very useful for drug development and basic research as well. Unfortunately, it is both time-consuming and costly to determine the SNO sites purely based on biological experiments. Facing the explosive protein sequence data generated in the post-genomic era, we are challenged to develop automated vehicles for timely and effectively determining the SNO sites for uncharacterized proteins. To address the challenge, a new predictor called iSNO-AAPair was developed by taking into account the coupling effects for all the pairs formed by the nearest residues and the pairs by the next nearest residues along protein chains. The cross-validation results on a state-of-the-art benchmark have shown that the new predictor outperformed the existing predictors. The same was true when tested by the independent proteins whose experimental SNO sites were known. A user-friendly web-server for iSNO-AAPair was established at http://app.aporc.org/iSNO-AAPair/, by which users can easily obtain their desired results without the need to follow the mathematical equations involved during its development.",2013 Oct 3,"['Xu, Yan', 'Shao, Xiao-Jian', 'Wu, Ling-Yun', 'Deng, Nai-Yang', 'Chou, Kuo-Chen']",PeerJ,,,False
35cf9c43b3b1028de85e24946f7bbc0436b24190,PMC,iSNO-AAPair: incorporating amino acid pairwise coupling into PseAAC for predicting cysteine S-nitrosylation sites in proteins,http://dx.doi.org/10.7717/peerj.171,PMC3792191,24109555,CC BY,"As one of the most important and universal posttranslational modifications (PTMs) of proteins, S-nitrosylation (SNO) plays crucial roles in a variety of biological processes, including the regulation of cellular dynamics and many signaling events. Knowledge of SNO sites in proteins is very useful for drug development and basic research as well. Unfortunately, it is both time-consuming and costly to determine the SNO sites purely based on biological experiments. Facing the explosive protein sequence data generated in the post-genomic era, we are challenged to develop automated vehicles for timely and effectively determining the SNO sites for uncharacterized proteins. To address the challenge, a new predictor called iSNO-AAPair was developed by taking into account the coupling effects for all the pairs formed by the nearest residues and the pairs by the next nearest residues along protein chains. The cross-validation results on a state-of-the-art benchmark have shown that the new predictor outperformed the existing predictors. The same was true when tested by the independent proteins whose experimental SNO sites were known. A user-friendly web-server for iSNO-AAPair was established at http://app.aporc.org/iSNO-AAPair/, by which users can easily obtain their desired results without the need to follow the mathematical equations involved during its development.",2013 Oct 3,"['Xu, Yan', 'Shao, Xiao-Jian', 'Wu, Ling-Yun', 'Deng, Nai-Yang', 'Chou, Kuo-Chen']",PeerJ,,,True
01110a24b6ce133ae80d21a36c7994e364ba296c,PMC,Feature Selection Methods for Identifying Genetic Determinants of Host Species in RNA Viruses,http://dx.doi.org/10.1371/journal.pcbi.1003254,PMC3794897,24130470,CC BY,"Despite environmental, social and ecological dependencies, emergence of zoonotic viruses in human populations is clearly also affected by genetic factors which determine cross-species transmission potential. RNA viruses pose an interesting case study given their mutation rates are orders of magnitude higher than any other pathogen – as reflected by the recent emergence of SARS and Influenza for example. Here, we show how feature selection techniques can be used to reliably classify viral sequences by host species, and to identify the crucial minority of host-specific sites in pathogen genomic data. The variability in alleles at those sites can be translated into prediction probabilities that a particular pathogen isolate is adapted to a given host. We illustrate the power of these methods by: 1) identifying the sites explaining SARS coronavirus differences between human, bat and palm civet samples; 2) showing how cross species jumps of rabies virus among bat populations can be readily identified; and 3) de novo identification of likely functional influenza host discriminant markers.",2013 Oct 10,"['Aguas, Ricardo', 'Ferguson, Neil M.']",PLoS Comput Biol,,,True
70943b05f17f2b7620ca6cc063b95ba2d7e8aab3,PMC,"Evaluation of the Replication, Pathogenicity, and Immunogenicity of Avian Paramyxovirus (APMV) Serotypes 2, 3, 4, 5, 7, and 9 in Rhesus Macaques",http://dx.doi.org/10.1371/journal.pone.0075456,PMC3794941,24130713,CC0,"Avian paramyxoviruses (APMV) serotypes 1–9 are frequently isolated from domestic and wild birds worldwide. APMV-1 (also called Newcastle disease virus, NDV) is attenuated in non-human primates and is being developed as a candidate human vaccine vector. The vector potential of the other serotypes was unknown. In the present study, we evaluated nine different biologically- or recombinantly-derived APMV strains for the ability to replicate and cause disease in rhesus macaque model. Five of the viruses were: biologically-derived wild type (wt) APMV-2, -3, -5, -7 and -9. Another virus was a recombinant (r) version of wt APMV-4. The remaining three viruses were versions of wt rAPMV-2, -4 and -7 in which the F cleavage site had been modified to be multi-basic. Rhesus macaques were inoculated intranasally and intratracheally and monitored for clinical disease, virus shedding from the upper and lower respiratory tract, and seroconversion. Virus shedding was not detected for wt APMV-5. Very limited shedding was detected for wt rAPMV-4 and modified rAPMV-4, and only in a subset of animals. Shedding by the other viruses was detected in every infected animal, and usually from both the upper and lower respiratory tract. In particular, shedding over a number of days in every animal was observed for modified rAPMV-2, wt APMV-7, and modified rAPMV-7. Modification of the F protein cleavage site appeared to increase shedding by wt rAPMV-2 and marginally by wt rAPMV-4. All APMVs except wt APMV-5 induced a virus-specific serum antibody response in all infected animals. None of the animals exhibited any clinical disease signs. These results indicate that APMVs 2, 3, 4, 7, and 9 are competent to infect non-human primates, but are moderately-to-highly restricted, depending on the serotype. This suggests that they are not likely to significantly infect primates in nature, and represent promising attenuated candidates for vector development.",2013 Oct 10,"['Khattar, Sunil K.', 'Nayak, Baibaswata', 'Kim, Shin-Hee', 'Xiao, Sa', 'Samal, Sweety', 'Paldurai, Anandan', 'Buchholz, Ursula J.', 'Collins, Peter L.', 'Samal, Siba K.']",PLoS One,,,True
bdb16338832867fb4c294b2694e8e23da78f3597,PMC,Caspase-1 Promotes Epstein-Barr Virus Replication by Targeting the Large Tegument Protein Deneddylase to the Nucleus of Productively Infected Cells,http://dx.doi.org/10.1371/journal.ppat.1003664,PMC3795028,24130483,CC BY,"The large tegument proteins of herpesviruses contain N-terminal cysteine proteases with potent ubiquitin and NEDD8-specific deconjugase activities, but the function of the enzymes during virus replication remains largely unknown. Using as model BPLF1, the homologue encoded by Epstein-Barr virus (EBV), we found that induction of the productive virus cycle does not affect the total level of ubiquitin-conjugation but is accompanied by a BPLF1-dependent decrease of NEDD8-adducts and accumulation of free NEDD8. Expression of BPLF1 promotes cullin degradation and the stabilization of cullin-RING ligases (CRLs) substrates in the nucleus, while cytoplasmic CRLs and their substrates are not affected. The inactivation of nuclear CRLs is reversed by the N-terminus of CAND1, which inhibits the binding of BPLF1 to cullins and prevents efficient viral DNA replication. Targeting of the deneddylase activity to the nucleus is dependent on processing of the catalytic N-terminus by caspase-1. Inhibition of caspase-1 severely impairs viral DNA synthesis and the release of infectious virus, pointing a previously unrecognized role of the cellular response to danger signals triggered by EBV reactivation in promoting virus replication.",2013 Oct 10,"['Gastaldello, Stefano', 'Chen, Xinsong', 'Callegari, Simone', 'Masucci, Maria G.']",PLoS Pathog,,,True
7dbdecefcd59460800cc11324be0595779ffde80,PMC,Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody,http://dx.doi.org/10.1371/journal.ppat.1003684,PMC3795035,24130486,CC0,"The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naïve antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines.",2013 Oct 10,"['Xu, Kai', 'Rockx, Barry', 'Xie, Yihu', 'DeBuysscher, Blair L.', 'Fusco, Deborah L.', 'Zhu, Zhongyu', 'Chan, Yee-Peng', 'Xu, Yan', 'Luu, Truong', 'Cer, Regina Z.', 'Feldmann, Heinz', 'Mokashi, Vishwesh', 'Dimitrov, Dimiter S.', 'Bishop-Lilly, Kimberly A.', 'Broder, Christopher C.', 'Nikolov, Dimitar B.']",PLoS Pathog,,,True
06c949be75a56cbb6228368dec7580bfbb638141,PMC,Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody,http://dx.doi.org/10.1371/journal.ppat.1003684,PMC3795035,24130486,CC0,"The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naïve antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines.",2013 Oct 10,"['Xu, Kai', 'Rockx, Barry', 'Xie, Yihu', 'DeBuysscher, Blair L.', 'Fusco, Deborah L.', 'Zhu, Zhongyu', 'Chan, Yee-Peng', 'Xu, Yan', 'Luu, Truong', 'Cer, Regina Z.', 'Feldmann, Heinz', 'Mokashi, Vishwesh', 'Dimitrov, Dimiter S.', 'Bishop-Lilly, Kimberly A.', 'Broder, Christopher C.', 'Nikolov, Dimitar B.']",PLoS Pathog,,,False
2064f80647340c485e6143344cfe4223e8b08e2d,PMC,Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody,http://dx.doi.org/10.1371/journal.ppat.1003684,PMC3795035,24130486,CC0,"The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naïve antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines.",2013 Oct 10,"['Xu, Kai', 'Rockx, Barry', 'Xie, Yihu', 'DeBuysscher, Blair L.', 'Fusco, Deborah L.', 'Zhu, Zhongyu', 'Chan, Yee-Peng', 'Xu, Yan', 'Luu, Truong', 'Cer, Regina Z.', 'Feldmann, Heinz', 'Mokashi, Vishwesh', 'Dimitrov, Dimiter S.', 'Bishop-Lilly, Kimberly A.', 'Broder, Christopher C.', 'Nikolov, Dimitar B.']",PLoS Pathog,,,False
221e182716d5ecbba8538ec7fda997030bc173c7,PMC,Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody,http://dx.doi.org/10.1371/journal.ppat.1003684,PMC3795035,24130486,CC0,"The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naïve antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines.",2013 Oct 10,"['Xu, Kai', 'Rockx, Barry', 'Xie, Yihu', 'DeBuysscher, Blair L.', 'Fusco, Deborah L.', 'Zhu, Zhongyu', 'Chan, Yee-Peng', 'Xu, Yan', 'Luu, Truong', 'Cer, Regina Z.', 'Feldmann, Heinz', 'Mokashi, Vishwesh', 'Dimitrov, Dimiter S.', 'Bishop-Lilly, Kimberly A.', 'Broder, Christopher C.', 'Nikolov, Dimitar B.']",PLoS Pathog,,,False
f2df4fc3c60338755fd23da3d7e01c0455e20745,PMC,Complete Genome Sequence of a Nephropathogenic Infectious Bronchitis Virus Strain Isolated in China,http://dx.doi.org/10.1128/genomeA.00815-13,PMC3795213,24115543,CC BY,"Infectious bronchitis virus (IBV) causes tremendous economic losses to the poultry industry. Here, we report the complete genome analysis results for a new natural recombination nephropathogenic IBV strain named SAIBK, which was isolated in the Sichuan province of China in 2005.",2013 Oct 10,"['Yang, Jing-tian', 'Ma, Bing-cun']",Genome Announc,,,True
5143bcbf109f693de355d2512a5810ed93a3072a,PMC,Exploring a Proposed WHO Method to Determine Thresholds for Seasonal Influenza Surveillance,http://dx.doi.org/10.1371/journal.pone.0077244,PMC3795663,24146973,CC BY,"INTRODUCTION: Health authorities find thresholds useful to gauge the start and severity of influenza seasons. We explored a method for deriving thresholds proposed in an influenza surveillance manual published by the World Health Organization (WHO). METHODS: For 2002-2011, we analysed two routine influenza-like-illness (ILI) datasets, general practice sentinel surveillance and a locum medical service sentinel surveillance, plus laboratory data and hospital admissions for influenza. For each sentinel dataset, we created two composite variables from the product of weekly ILI data and the relevant laboratory data, indicating the proportion of tested specimens that were positive. For all datasets, including the composite datasets, we aligned data on the median week of peak influenza or ILI activity and assigned three threshold levels: seasonal threshold, determined by inspection; and two intensity thresholds termed average and alert thresholds, determined by calculations of means, medians, confidence intervals (CI) and percentiles. From the thresholds, we compared the seasonal onset, end and intensity across all datasets from 2002-2011. Correlation between datasets was assessed using the mean correlation coefficient. RESULTS: The median week of peak activity was week 34 for all datasets, except hospital data (week 35). Means and medians were comparable and the 90% upper CIs were similar to the 95(th) percentiles. Comparison of thresholds revealed variations in defining the start of a season but good agreement in describing the end and intensity of influenza seasons, except in hospital admissions data after the pandemic year of 2009. The composite variables improved the agreements between the ILI and other datasets. Datasets were well correlated, with mean correlation coefficients of >0.75 for a range of combinations. CONCLUSIONS: Thresholds for influenza surveillance are easily derived from historical surveillance and laboratory data using the approach proposed by WHO. Use of composite variables is helpful for describing influenza season characteristics.",2013 Oct 11,"['Tay, Ee Laine', 'Grant, Kristina', 'Kirk, Martyn', 'Mounts, Anthony', 'Kelly, Heath']",PLoS One,,,True
46ffe37cdfe520a31dadf0a3308b1f7f98d4295d,PMC,Targeted Deletion of FGL2 Leads to Increased Early Viral Replication and Enhanced Adaptive Immunity in a Murine Model of Acute Viral Hepatitis Caused by LCMV WE,http://dx.doi.org/10.1371/journal.pone.0072309,PMC3795679,24146739,CC BY,"Mounting effective innate and adaptive immune responses are critical for viral clearance and the generation of long lasting immunity. It is known that production of inhibitory factors may result in the inability of the host to clear viruses, resulting in chronic viral persistence. Fibrinogen-like protein 2 (FGL2) has been identified as a novel effector molecule of CD4(+)CD25(+) Foxp3(+) regulatory T (Treg) cells that inhibits immune activity by binding to FCγRIIB expressed primarily on antigen presenting cells (APC). In this study, we show that infection of mice with Lymphocytic Choriomeningitis Virus WE (LCMV WE) leads to increased plasma levels of FGL2, which were detected as early as 2 days post-infection (pi) and persisted until day 50 pi. Mice deficient in FGL2 (fgl2(−/−)) had increased viral titers of LCMV WE in the liver early p.i but cleared the virus by day 12 similar to wild type mice. Dendritic cells (DC) isolated from the spleens of LCMV WE infected fgl2(−/−) had increased expression of the DC maturation markers CD80 and MHC Class II compared to wild type (fgl2(+/+)). Frequencies of CD8(+) and CD4(+) T cells producing IFNγ in response to ex vivo peptide re-stimulation isolated from the spleen and lymph nodes were also increased in LCMV WE infected fgl2 (−/−) mice. Increased frequencies of CD8(+) T cells specific for LCMV tetramers GP(33) and NP(396) were detected within the liver of fgl2(−/−) mice. Plasma from fgl2(−/−) mice contained higher titers of total and neutralizing anti-LCMV antibody. Enhanced anti-viral immunity in fgl2(−/−) mice was associated with increased levels of serum alanine transaminase (ALT), hepatic necrosis and inflammation following LCMV WE infection. These data demonstrate that targeting FGL2 leads to early increased viral replication but enhanced anti-viral adaptive T & B cell responses. Targeting FGL2 may enhance the efficacy of current anti-viral therapies for hepatotropic viruses.",2013 Oct 11,"['Khattar, Ramzi', 'Luft, Olga', 'Yavorska, Nataliya', 'Shalev, Itay', 'Phillips, M. James', 'Adeyi, Oyedele', 'Gao, Darrin', 'Bartczak, Agata', 'Urbanellis, Peter', 'Shyu, Wendy', 'Zhang, Jianhua', 'Manuel, Justin', 'Levy, Gary A.', 'Selzner, Nazia']",PLoS One,,,True
2fd0fccb43ad3cb1634370734ba27eaed2cf015a,PMC,Caveolin-1 Associated Adenovirus Entry into Human Corneal Cells,http://dx.doi.org/10.1371/journal.pone.0077462,PMC3795695,24147000,CC BY,"The cellular entry of viruses represents a critical area of study, not only for viral tropism, but also because viral entry dictates the nature of the immune response elicited upon infection. Epidemic keratoconjunctivitis (EKC), caused by viruses within human adenovirus species D (HAdV-D), is a severe, ocular surface infection associated with corneal inflammation. Clathrin-mediated endocytosis has previously been shown to play a critical role in entry of other HAdV species into many host cell types. However, HAdV-D endocytosis into corneal cells has not been extensively studied. Herein, we show an essential role for cholesterol rich, lipid raft microdomains and caveolin-1, in the entry of HAdV-D37 into primary human corneal fibroblasts. Cholesterol depletion using methyl-β-cyclodextrin (MβCD) profoundly reduced viral infection. When replenished with soluble cholesterol, the effect of MβCD was reversed, allowing productive viral infection. HAdV-D37 DNA was identified in caveolin-1 rich endosomal fractions after infection. Src kinase activity was also increased in caveolin-1 rich endosomal fractions after infection, and Src phosphorylation and CXCL1 induction were both decreased in caveolin-1-/- mice corneas compared to wild type mice. siRNA knock down of caveolin-1 in corneal cells reduced chemokine induction upon viral infection, and caveolin-1-/- mouse corneas showed reduced cellular entry of HAdV-D37. As a control, HAdV-C2, a non-corneal pathogen, appeared to utilize the caveolar pathway for entry into A549 cells, but failed to infect corneal cells entirely, indicating virus and cell specific tropism. Immuno-electron microscopy confirmed the presence of caveolin-1 in HAdV-D37-containing vesicles during the earliest stages of viral entry. Collectively, these experiments indicate for the first time that HAdV-D37 uses a lipid raft mediated caveolin-1 associated pathway for entry into corneal cells, and connects the processes of viral entry with downstream proinflammatory cell signaling.",2013 Oct 11,"['Yousuf, Mohammad A.', 'Zhou, Xiaohong', 'Mukherjee, Santanu', 'Chintakuntlawar, Ashish V.', 'Lee, Jeong Yoon', 'Ramke, Mirja', 'Chodosh, James', 'Rajaiya, Jaya']",PLoS One,,,True
80013c44d7d2d3949096511ad6fa424a2c740813,PMC,Influenza A virus-mediated priming enhances cytokine secretion by human dendritic cells infected with Streptococcus pneumoniae,http://dx.doi.org/10.1111/cmi.12122,PMC3798092,23421931,CC BY,"Secondary infections with Streptococcus pneumoniae (SP) are frequently observed following influenza A virus (IAV) infection and have a substantial impact on global health. Despite this, the basis for the disease progression is incompletely understood. To investigate the effect of co-infection on human monocyte-derived dendritic cells (MDDCs) we analysed the expression of clinically important pro-inflammatory and immune-modulatory cytokines. IAV infection or treatment with supernatants from IAV-infected cell cultures resulted in priming of the DCs which subsequently influenced the production of IL-12p70, as well as IL-6, following SP infection. Co-infection of the same cell was not required but this effect was dependent on the time, dose and duration of the infections, as well as pathogen viability, bacterial uptake and endosome acidification. Bacterially infected cells were characterized as the main producers of IL-12p70. Finally, we showed that type I interferons were primarily responsible for the priming of IL-12p70 that was observed by infection with IAV. These results provide a probable mechanism for the elevated levels of particular cytokines observed in IAV and SP co-infected cell cultures with implications for the pathogenic outcome observed during in vivo infection.",2013 Aug 14,"['Kuri, Thomas', 'Smed Sörensen, Anna', 'Thomas, Saskia', 'Karlsson Hedestam, Gunilla B', 'Normark, Staffan', 'Henriques-Normark, Birgitta', 'McInerney, Gerald M', 'Plant, Laura']",Cell Microbiol,,,True
463a646aaf5a4bee77ded050bb89bba468198344,PMC,Influenza A virus-mediated priming enhances cytokine secretion by human dendritic cells infected with Streptococcus pneumoniae,http://dx.doi.org/10.1111/cmi.12122,PMC3798092,23421931,CC BY,"Secondary infections with Streptococcus pneumoniae (SP) are frequently observed following influenza A virus (IAV) infection and have a substantial impact on global health. Despite this, the basis for the disease progression is incompletely understood. To investigate the effect of co-infection on human monocyte-derived dendritic cells (MDDCs) we analysed the expression of clinically important pro-inflammatory and immune-modulatory cytokines. IAV infection or treatment with supernatants from IAV-infected cell cultures resulted in priming of the DCs which subsequently influenced the production of IL-12p70, as well as IL-6, following SP infection. Co-infection of the same cell was not required but this effect was dependent on the time, dose and duration of the infections, as well as pathogen viability, bacterial uptake and endosome acidification. Bacterially infected cells were characterized as the main producers of IL-12p70. Finally, we showed that type I interferons were primarily responsible for the priming of IL-12p70 that was observed by infection with IAV. These results provide a probable mechanism for the elevated levels of particular cytokines observed in IAV and SP co-infected cell cultures with implications for the pathogenic outcome observed during in vivo infection.",2013 Aug 14,"['Kuri, Thomas', 'Smed Sörensen, Anna', 'Thomas, Saskia', 'Karlsson Hedestam, Gunilla B', 'Normark, Staffan', 'Henriques-Normark, Birgitta', 'McInerney, Gerald M', 'Plant, Laura']",Cell Microbiol,,,False
d5535b19156c0be39daefcb8fabb03cbcd43b4b1,PMC,Influenza A virus-mediated priming enhances cytokine secretion by human dendritic cells infected with Streptococcus pneumoniae,http://dx.doi.org/10.1111/cmi.12122,PMC3798092,23421931,CC BY,"Secondary infections with Streptococcus pneumoniae (SP) are frequently observed following influenza A virus (IAV) infection and have a substantial impact on global health. Despite this, the basis for the disease progression is incompletely understood. To investigate the effect of co-infection on human monocyte-derived dendritic cells (MDDCs) we analysed the expression of clinically important pro-inflammatory and immune-modulatory cytokines. IAV infection or treatment with supernatants from IAV-infected cell cultures resulted in priming of the DCs which subsequently influenced the production of IL-12p70, as well as IL-6, following SP infection. Co-infection of the same cell was not required but this effect was dependent on the time, dose and duration of the infections, as well as pathogen viability, bacterial uptake and endosome acidification. Bacterially infected cells were characterized as the main producers of IL-12p70. Finally, we showed that type I interferons were primarily responsible for the priming of IL-12p70 that was observed by infection with IAV. These results provide a probable mechanism for the elevated levels of particular cytokines observed in IAV and SP co-infected cell cultures with implications for the pathogenic outcome observed during in vivo infection.",2013 Aug 14,"['Kuri, Thomas', 'Smed Sörensen, Anna', 'Thomas, Saskia', 'Karlsson Hedestam, Gunilla B', 'Normark, Staffan', 'Henriques-Normark, Birgitta', 'McInerney, Gerald M', 'Plant, Laura']",Cell Microbiol,,,False
85a50734ee9254706c0d4a338a27da6d8e75b0cb,PMC,Influenza A virus-mediated priming enhances cytokine secretion by human dendritic cells infected with Streptococcus pneumoniae,http://dx.doi.org/10.1111/cmi.12122,PMC3798092,23421931,CC BY,"Secondary infections with Streptococcus pneumoniae (SP) are frequently observed following influenza A virus (IAV) infection and have a substantial impact on global health. Despite this, the basis for the disease progression is incompletely understood. To investigate the effect of co-infection on human monocyte-derived dendritic cells (MDDCs) we analysed the expression of clinically important pro-inflammatory and immune-modulatory cytokines. IAV infection or treatment with supernatants from IAV-infected cell cultures resulted in priming of the DCs which subsequently influenced the production of IL-12p70, as well as IL-6, following SP infection. Co-infection of the same cell was not required but this effect was dependent on the time, dose and duration of the infections, as well as pathogen viability, bacterial uptake and endosome acidification. Bacterially infected cells were characterized as the main producers of IL-12p70. Finally, we showed that type I interferons were primarily responsible for the priming of IL-12p70 that was observed by infection with IAV. These results provide a probable mechanism for the elevated levels of particular cytokines observed in IAV and SP co-infected cell cultures with implications for the pathogenic outcome observed during in vivo infection.",2013 Aug 14,"['Kuri, Thomas', 'Smed Sörensen, Anna', 'Thomas, Saskia', 'Karlsson Hedestam, Gunilla B', 'Normark, Staffan', 'Henriques-Normark, Birgitta', 'McInerney, Gerald M', 'Plant, Laura']",Cell Microbiol,,,False
da4856482e2820b8ef50403540207af6b0becde6,PMC,Influenza A virus-mediated priming enhances cytokine secretion by human dendritic cells infected with Streptococcus pneumoniae,http://dx.doi.org/10.1111/cmi.12122,PMC3798092,23421931,CC BY,"Secondary infections with Streptococcus pneumoniae (SP) are frequently observed following influenza A virus (IAV) infection and have a substantial impact on global health. Despite this, the basis for the disease progression is incompletely understood. To investigate the effect of co-infection on human monocyte-derived dendritic cells (MDDCs) we analysed the expression of clinically important pro-inflammatory and immune-modulatory cytokines. IAV infection or treatment with supernatants from IAV-infected cell cultures resulted in priming of the DCs which subsequently influenced the production of IL-12p70, as well as IL-6, following SP infection. Co-infection of the same cell was not required but this effect was dependent on the time, dose and duration of the infections, as well as pathogen viability, bacterial uptake and endosome acidification. Bacterially infected cells were characterized as the main producers of IL-12p70. Finally, we showed that type I interferons were primarily responsible for the priming of IL-12p70 that was observed by infection with IAV. These results provide a probable mechanism for the elevated levels of particular cytokines observed in IAV and SP co-infected cell cultures with implications for the pathogenic outcome observed during in vivo infection.",2013 Aug 14,"['Kuri, Thomas', 'Smed Sörensen, Anna', 'Thomas, Saskia', 'Karlsson Hedestam, Gunilla B', 'Normark, Staffan', 'Henriques-Normark, Birgitta', 'McInerney, Gerald M', 'Plant, Laura']",Cell Microbiol,,,False
bfcb22212525a49970dc301582343e388fc5cfd6,PMC,Gargling for Oral Hygiene and the Development of Fever in Childhood: A Population Study in Japan,http://dx.doi.org/10.2188/jea.JE20100181,PMC3798579,22123226,CC BY,"BACKGROUND: Fever is one of the most common symptoms among children and is usually caused by respiratory infections. Although Japanese health authorities have long recommended gargling to prevent respiratory infections, its effectiveness among children is not clear. METHODS: The children in this observational study were enrolled from 145 nursery schools in Fukuoka City, Japan. Children in the exposure group were instructed to gargle at least once a day. The endpoints of this study were incidence of fever during the daytime and incidence of sickness absence. Differences among gargling agents for each endpoint were also analyzed. RESULTS: A total of 19 595 children aged 2 to 6 years were observed for 20 days (391 900 person-days). In multivariate logistic regression, the overall odds ratio (OR) for fever onset in the gargling group was significantly lower (OR = 0.68). In age-stratified analysis, ORs were significantly lower at age 2 (OR = 0.67), 4 (OR = 0.46), and 5 (OR = 0.41) years. Regarding sickness absence, the overall OR was 0.92 (not significant) in the gargling group. In age-stratified analysis, ORs were significantly lower at age 4 (OR = 0.68), 5 (OR = 0.59), and 6 (OR = 0.63) years. In subgroup analysis, significantly lower ORs for fever onset were observed for children who gargled with green tea (OR = 0.32), functional water (OR = 0.46), or tap water (OR = 0.70). However, the ORs were not significant for sickness absence. CONCLUSIONS: Gargling might be effective in preventing febrile diseases in children.",2012 Jan 5,"['Noda, Tatsuya', 'Ojima, Toshiyuki', 'Hayasaka, Shinya', 'Murata, Chiyoe', 'Hagihara, Akihito']",J Epidemiol,,,True
13d3cd2797da7eb9cc334821680a7b30badafa11,PMC,Interleukin 35: A Key Mediator of Suppression and the Propagation of Infectious Tolerance,http://dx.doi.org/10.3389/fimmu.2013.00315,PMC3798782,24151492,CC BY,"The importance of regulatory T cells (Tregs) in balancing the effector arm of the immune system is well documented, playing a central role in preventing autoimmunity, facilitating graft tolerance following organ transplantation, and having a detrimental impact on the development of anti-tumor immunity. These regulatory responses use a variety of mechanisms to mediate suppression, including soluble factors. While IL-10 and TGF-β are the most commonly studied immunosuppressive cytokines, the recently identified IL-35 has been shown to have potent suppressive function in vitro and in vivo. Furthermore, not only does IL-35 have the ability to directly suppress effector T cell responses, it is also able to expand regulatory responses by propagating infectious tolerance and generating a potent population of IL-35-expressing inducible Tregs. In this review, we summarize research characterizing the structure and function of IL-35, examine its role in disease, and discuss how it can contribute to the induction of a distinct population of inducible Tregs.",2013 Oct 18,"['Olson, Brian M.', 'Sullivan, Jeremy A.', 'Burlingham, William J.']",Front Immunol,,,True
e458fadd59e9f9ac952f6c40f283b14071174259,PMC,Role of Natural Killer and Gamma-Delta T cells in West Nile Virus Infection,http://dx.doi.org/10.3390/v5092298,PMC3798903,24061543,CC BY,"Natural Killer (NK) cells and Gamma-delta T cells are both innate lymphocytes that respond rapidly and non-specifically to viral infection and other pathogens. They are also known to form a unique link between innate and adaptive immunity. Although they have similar immune features and effector functions, accumulating evidence in mice and humans suggest these two cell types have distinct roles in the control of infection by West Nile virus (WNV), a re-emerging pathogen that has caused fatal encephalitis in North America over the past decade. This review will discuss recent studies on these two cell types in protective immunity and viral pathogenesis during WNV infection.",2013 Sep 20,"['Wang, Tian', 'Welte, Thomas']",Viruses,,,True
e466de47aa170d1f457c5fd9e1b01ae0ba0549cc,PMC,"Genetic Analysis of West Nile Virus Isolates from an Outbreak in Idaho, United States, 2006–2007",http://dx.doi.org/10.3390/ijerph10094486,PMC3799518,24065039,CC BY,"West Nile virus (WNV) appeared in the U.S. in 1999 and has since become endemic, with yearly summer epidemics causing tens of thousands of cases of serious disease over the past 14 years. Analysis of WNV strains isolated during the 2006–2007 epidemic seasons demonstrates that a new genetic variant had emerged coincidentally with an intense outbreak in Idaho during 2006. The isolates belonging to the new variant carry a 13 nt deletion, termed ID-Δ13, located at the variable region of the 3′UTR, and are genetically related. The analysis of deletions and insertions in the 3′UTR of two major lineages of WNV revealed the presence of conserved repeats and two indel motifs in the variable region of the 3′UTR. One human and two bird isolates from the Idaho 2006–2007 outbreaks were sequenced using Illumina technology and within-host variability was analyzed. Continued monitoring of new genetic variants is important for public health as WNV continues to evolve.",2013 Sep 23,"['Grinev, Andriyan', 'Chancey, Caren', 'Añez, Germán', 'Ball, Christopher', 'Winkelman, Valerie', 'Williamson, Phillip', 'Foster, Gregory A.', 'Stramer, Susan L.', 'Rios, Maria']",Int J Environ Res Public Health,,,True
31fd4d2067fb03f503ce03d16e323020b9f1d219,PMC,"Genetic Analysis of West Nile Virus Isolates from an Outbreak in Idaho, United States, 2006–2007",http://dx.doi.org/10.3390/ijerph10094486,PMC3799518,24065039,CC BY,"West Nile virus (WNV) appeared in the U.S. in 1999 and has since become endemic, with yearly summer epidemics causing tens of thousands of cases of serious disease over the past 14 years. Analysis of WNV strains isolated during the 2006–2007 epidemic seasons demonstrates that a new genetic variant had emerged coincidentally with an intense outbreak in Idaho during 2006. The isolates belonging to the new variant carry a 13 nt deletion, termed ID-Δ13, located at the variable region of the 3′UTR, and are genetically related. The analysis of deletions and insertions in the 3′UTR of two major lineages of WNV revealed the presence of conserved repeats and two indel motifs in the variable region of the 3′UTR. One human and two bird isolates from the Idaho 2006–2007 outbreaks were sequenced using Illumina technology and within-host variability was analyzed. Continued monitoring of new genetic variants is important for public health as WNV continues to evolve.",2013 Sep 23,"['Grinev, Andriyan', 'Chancey, Caren', 'Añez, Germán', 'Ball, Christopher', 'Winkelman, Valerie', 'Williamson, Phillip', 'Foster, Gregory A.', 'Stramer, Susan L.', 'Rios, Maria']",Int J Environ Res Public Health,,,True
3cf1d3f730cadc87a4392893ee1a6d4da9cb5efb,PMC,The Serological and Virological Investigation of Canine Adenovirus Infection on the Dogs,http://dx.doi.org/10.1155/2013/587024,PMC3800580,24223508,CC BY,"Two types of Canine Adenovirus (CAVs), Canine Adenovirus type 1 (CAV-1), the virus which causes infectious canine hepatitis, and Canine Adenovirus type 2 (CAV-2), which causes canine infectious laryngotracheitis, have been found in dogs. In this study, blood samples taken from 111 dogs, which were admitted to the Internal Medicine Clinic of Selcuk University, Faculty of Veterinary Medicine, with clinical symptoms. Seventy-seven dogs were sampled from Isparta and Burdur dog shelters by random sampling, regardless of the clinical findings. Dogs showed a systemic disease, characterized by fever, diarrhea, vomiting, oculonasal discharge, conjunctivitis, severe moist cough, signs of pulmonary disease and dehydration. Two dogs had corneal opacity and photophobia. In serological studies, 188 serum samples were investigated on the presence of CAV antibodies by ELISA. Total 103 (103/188–54.7%) blood samples were detected to be positive for CAV antibodies by ELISA. However, 85 (85/188–45.2%) blood samples were negative. Blood leukocyte samples from dogs were processed and inoculated onto confluent monolayers of MDCK cells using standard virological techniques. After third passage, cells were examined by direct immunoflourescence test for virus isolation. But positive result was not detected. In conclusion, this study clearly demonstrates the high prevalence of CAV infection in dogs.",2013 Sep 24,"['Bulut, Oya', 'Yapici, Orhan', 'Avci, Oguzhan', 'Simsek, Atilla', 'Atli, Kamil', 'Dik, Irmak', 'Yavru, Sibel', 'Hasircioglu, Sibel', 'Kale, Mehmet', 'Mamak, Nuri']",ScientificWorldJournal,,,True
f86ac2580002e6b374ec325717eeee73e84af1c5,PMC,Steroid-Associated Hip Joint Collapse in Bipedal Emus,http://dx.doi.org/10.1371/journal.pone.0076797,PMC3804596,24204675,CC BY,"In this study we established a bipedal animal model of steroid-associated hip joint collapse in emus for testing potential treatment protocols to be developed for prevention of steroid-associated joint collapse in preclinical settings. Five adult male emus were treated with a steroid-associated osteonecrosis (SAON) induction protocol using combination of pulsed lipopolysaccharide (LPS) and methylprednisolone (MPS). Additional three emus were used as normal control. Post-induction, emu gait was observed, magnetic resonance imaging (MRI) was performed, and blood was collected for routine examination, including testing blood coagulation and lipid metabolism. Emus were sacrificed at week 24 post-induction, bilateral femora were collected for micro-computed tomography (micro-CT) and histological analysis. Asymmetric limping gait and abnormal MRI signals were found in steroid-treated emus. SAON was found in all emus with a joint collapse incidence of 70%. The percentage of neutrophils (Neut %) and parameters on lipid metabolism significantly increased after induction. Micro-CT revealed structure deterioration of subchondral trabecular bone. Histomorphometry showed larger fat cell fraction and size, thinning of subchondral plate and cartilage layer, smaller osteoblast perimeter percentage and less blood vessels distributed at collapsed region in SAON group as compared with the normal controls. Scanning electron microscope (SEM) showed poor mineral matrix and more osteo-lacunae outline in the collapsed region in SAON group. The combination of pulsed LPS and MPS developed in the current study was safe and effective to induce SAON and deterioration of subchondral bone in bipedal emus with subsequent femoral head collapse, a typical clinical feature observed in patients under pulsed steroid treatment. In conclusion, bipedal emus could be used as an effective preclinical experimental model to evaluate potential treatment protocols to be developed for prevention of ON-induced hip joint collapse in patients.",2013 Oct 21,"['Zheng, Li-Zhen', 'Liu, Zhong', 'Lei, Ming', 'Peng, Jiang', 'He, Yi-Xin', 'Xie, Xin-Hui', 'Man, Chi-Wai', 'Huang, Le', 'Wang, Xin-Luan', 'Fong, Daniel Tik-Pui', 'Xiao, De-Ming', 'Wang, Da-Ping', 'Chen, Yang', 'Feng, Jian Q.', 'Liu, Ying', 'Zhang, Ge', 'Qin, Ling']",PLoS One,,,True
5e3a5143a77a6faeb480c65a23137616c14e7bad,PMC,Inhibition of Influenza H7 Hemagglutinin-Mediated Entry,http://dx.doi.org/10.1371/journal.pone.0076363,PMC3806803,24194835,CC BY,"The recent outbreak of H7N9 influenza in China is of high concern to public health. H7 hemagglutinin (HA) plays a critical role in influenza entry and thus HA presents an attractive target for antivirals. Previous studies have suggested that the small molecule tert-butyl hydroquinone (TBHQ) inhibits the entry of influenza H3 HA by binding to the stem loop of HA and stabilizing the neutral pH conformation of HA, thereby disrupting the membrane fusion step. Based on amino acid sequence, structure and immunogenicity, H7 is a related Group 2 HA. In this work we show, using a pseudovirus entry assay, that TBHQ inhibits H7 HA-mediated entry, as well as H3 HA-mediated entry, with an IC50∼6 µM. Using NMR, we show that TBHQ binds to the H7 stem loop region. STD NMR experiments indicate that the aromatic ring of TBHQ makes extensive contact with the H7 HA surface. Limited proteolysis experiments indicate that TBHQ inhibits influenza entry by stabilizing the H7 HA neutral pH conformation. Together, this work suggests that the stem loop region of H7 HA is an attractive target for therapeutic intervention and that TBHQ, which is a widely used food preservative, is a promising lead compound.",2013 Oct 23,"['Antanasijevic, Aleksandar', 'Cheng, Han', 'Wardrop, Duncan J.', 'Rong, Lijun', 'Caffrey, Michael']",PLoS One,,,True
447da2087b2d876e228b40eb8a29446bfd585499,PMC,Co-Infections in Children Hospitalised for Bronchiolitis: Role of Roomsharing,http://dx.doi.org/10.4021/jocmr1556w,PMC3808260,24171054,CC BY,"BACKGROUND: Bronchiolitis is a major cause for hospitalisation in young children during the winter season, with respiratory syncytial virus (RSV) as the main causative virus. Apart from standard hygiene measures, cohorting of RSV-infected patients separately from RSV-negative patients is frequently applied to prevent cross-infection, although evidence to support this practice is lacking. The objective is to evaluate the risk of room sharing between RSV-positive and RSV-negative patients. METHODS: We performed a prospective observational cohort study in children < 2 years hospitalised with acute bronchiolitis. During the first day of admission, patients shared one room, pending results of virological diagnosis (PCR). When diagnostic results were available, RSV-positive and RSV-negative patients were separated. Standard hygienic measures (gowns, gloves, masks, hand washing) were used in all patients. RESULTS: We included 48 patients (83% RSV-positive). Co-infection was found in nine patients at admission, and two during hospitalisation (23%). The two patients with acquired co-infection had been nursed in a single room during the entire admission. None of 37 patients sharing a room with other bronchiolitis patients (20 with patients with a different virus) were co-infected during admission. Disease severity in co-infection was not worse than in mono-infection. CONCLUSION: One in five patients with bronchiolitis was co-infected, but co-infection acquired during admission was rare and was not associated with more severe disease. Room sharing between RSV-positive and RSV-negative patients (on the first day of admission) did not influence the risk of co-infection, suggesting that cohorting of RSV-infected patients separate from non-RSV-infected patients may not be indicated.",2013 Dec 12,"['Bekhof, Jolita', 'Bakker, Joline', 'Reimink, Roelien', 'Wessels, Mirjam', 'Langenhorst, Veerle', 'Brand, Paul L.P.', 'Ruijs, Gijs J.H.M.']",J Clin Med Res,,,True
bda64532f4a16e2885868385170f8bc89ab8f789,PMC,Eukaryotic Initiation Factor 2α - a Downstream Effector of Mammalian Target of Rapamycin - Modulates DNA Repair and Cancer Response to Treatment,http://dx.doi.org/10.1371/journal.pone.0077260,PMC3808413,24204783,CC BY,"In an effort to circumvent resistance to rapamycin – an mTOR inhibitor - we searched for novel rapamycin-downstream-targets that may be key players in the response of cancer cells to therapy. We found that rapamycin, at nM concentrations, increased phosphorylation of eukaryotic initiation factor (eIF) 2α in rapamycin-sensitive and estrogen-dependent MCF-7 cells, but had only a minimal effect on eIF2α phosphorylation in the rapamycin-insensitive triple-negative MDA-MB-231 cells. Addition of salubrinal – an inhibitor of eIF2α dephosphorylation – decreased expression of a surface marker associated with capacity for self renewal, increased senescence and induced clonogenic cell death, suggesting that excessive phosphorylation of eIF2α is detrimental to the cells' survival. Treating cells with salubrinal enhanced radiation-induced increase in eIF2α phosphorylation and clonogenic death and showed that irradiated cells are more sensitive to increased eIF2α phosphorylation than non-irradiated ones. Similar to salubrinal - the phosphomimetic eIF2α variant - S51D - increased sensitivity to radiation, and both abrogated radiation-induced increase in breast cancer type 1 susceptibility gene, thus implicating enhanced phosphorylation of eIF2α in modulation of DNA repair. Indeed, salubrinal inhibited non-homologous end joining as well as homologous recombination repair of double strand breaks that were induced by I-SceI in green fluorescent protein reporter plasmids. In addition to its effect on radiation, salubrinal enhanced eIF2α phosphorylation and clonogenic death in response to the histone deacetylase inhibitor – vorinostat. Finally, the catalytic competitive inhibitor of mTOR - Ku-0063794 - increased phosphorylation of eIF2α demonstrating further the involvement of mTOR activity in modulating eIF2α phosphorylation. These experiments suggest that excessive phosphorylation of eIF2α decreases survival of cancer cells; making eIF2α a worthy target for drug development, with the potential to enhance the cytotoxic effects of established anti-neoplastic therapies and circumvent resistance to rapalogues and possibly to other drugs that inhibit upstream components of the mTOR pathway.",2013 Oct 25,"['Tuval-Kochen, Liron', 'Paglin, Shoshana', 'Keshet, Gilmor', 'Lerenthal, Yaniv', 'Nakar, Charles', 'Golani, Tamar', 'Toren, Amos', 'Yahalom, Joachim', 'Pfeffer, Raphael', 'Lawrence, Yaacov']",PLoS One,,,True
36b5106f87b0cf684bca0e39767d48caedc47d43,PMC,The Role of Mannose-Binding Lectin in Severe Sepsis and Septic Shock,http://dx.doi.org/10.1155/2013/625803,PMC3808714,24223476,CC BY,"Severe sepsis and septic shock are a primary cause of death in patients in intensive care unit (ICU). Investigations upon genetic susceptibility profile to systemic complications during severe infections are a field of increasing scientific interest. Particularly when adaptive immune system is compromised or immature, innate immunity plays a key role in the immediate defense against invasive pathogens. Mannose-binding lectin (MBL) is a serum protein that recognizes a wide range of pathogenic microorganisms and activates complement cascade via the antibody-independent pathway. More than 30% of humans harbor mutations in MBL gene (MBL2) resulting in reduced plasmatic levels and activity. Increased risk of infection acquisition has been largely documented in MBL-deficient patients, but the real impact of this form of innate immunosuppression upon clinical outcome is not clear. In critically ill patients higher incidence and worse prognosis of severe sepsis/septic shock appear to be associated with low-producers haplotypes. However an excess of MBL activation might be also harmful due to the possibility of an unbalanced proinflammatory response and an additional host injury. Strategies of replacement therapies in critically ill patients with severe infections are under investigation but still far to be applied in clinical practice.",2013 Oct 2,"['De Pascale, Gennaro', 'Cutuli, Salvatore Lucio', 'Pennisi, Mariano Alberto', 'Antonelli, Massimo']",Mediators Inflamm,,,True
039ca136c69c998e9a2677259d9de2941a13304a,PMC,Adaptation of novel H7N9 influenza A virus to human receptors,http://dx.doi.org/10.1038/srep03058,PMC3808826,24162312,CC BY,"The emergence of the novel H7N9 influenza A virus (IAV) has caused global concerns about the ability of this virus to spread between humans. Analysis of the receptor-binding properties of this virus using a recombinant protein approach in combination with fetuin-binding, glycan array and human tissue-binding assays demonstrates increased binding of H7 to both α2-6 and α2-8 sialosides as well as reduced binding to α2-3-linked SIAs compared to a closely related avian H7N9 virus from 2008. These differences could be attributed to substitutions Q226L and G186V. Analysis of the enzymatic activity of the neuraminidase N9 protein indicated a reduced sialidase activity, consistent with the reduced binding of H7 to α2-3 sialosides. However, the novel H7N9 virus still preferred binding to α2-3- over α2-6-linked SIAs and was not able to efficiently bind to epithelial cells of human trachea in contrast to seasonal IAV, consistent with its limited human-to-human transmission.",2013 Oct 28,"['Dortmans, J. C. F. M.', 'Dekkers, J.', 'Wickramasinghe, I. N. Ambepitiya', 'Verheije, M. H.', 'Rottier, P. J. M.', 'van Kuppeveld, F. J. M.', 'de Vries, E.', 'de Haan, C. A. M.']",Sci Rep,,,True
d31c808b7108ee70653f288622745ce73ca14adf,PMC,Adaptation of novel H7N9 influenza A virus to human receptors,http://dx.doi.org/10.1038/srep03058,PMC3808826,24162312,CC BY,"The emergence of the novel H7N9 influenza A virus (IAV) has caused global concerns about the ability of this virus to spread between humans. Analysis of the receptor-binding properties of this virus using a recombinant protein approach in combination with fetuin-binding, glycan array and human tissue-binding assays demonstrates increased binding of H7 to both α2-6 and α2-8 sialosides as well as reduced binding to α2-3-linked SIAs compared to a closely related avian H7N9 virus from 2008. These differences could be attributed to substitutions Q226L and G186V. Analysis of the enzymatic activity of the neuraminidase N9 protein indicated a reduced sialidase activity, consistent with the reduced binding of H7 to α2-3 sialosides. However, the novel H7N9 virus still preferred binding to α2-3- over α2-6-linked SIAs and was not able to efficiently bind to epithelial cells of human trachea in contrast to seasonal IAV, consistent with its limited human-to-human transmission.",2013 Oct 28,"['Dortmans, J. C. F. M.', 'Dekkers, J.', 'Wickramasinghe, I. N. Ambepitiya', 'Verheije, M. H.', 'Rottier, P. J. M.', 'van Kuppeveld, F. J. M.', 'de Vries, E.', 'de Haan, C. A. M.']",Sci Rep,,,True
c57fb53010f62a669421b0f4894a26e22e0e496c,PMC,GenomeFingerprinter: The Genome Fingerprint and the Universal Genome Fingerprint Analysis for Systematic Comparative Genomics,http://dx.doi.org/10.1371/journal.pone.0077912,PMC3812135,24205026,CC BY,"BACKGROUND: No attention has been paid on comparing a set of genome sequences crossing genetic components and biological categories with far divergence over large size range. We define it as the systematic comparative genomics and aim to develop the methodology. RESULTS: First, we create a method, GenomeFingerprinter, to unambiguously produce a set of three-dimensional coordinates from a sequence, followed by one three-dimensional plot and six two-dimensional trajectory projections, to illustrate the genome fingerprint of a given genome sequence. Second, we develop a set of concepts and tools, and thereby establish a method called the universal genome fingerprint analysis (UGFA). Particularly, we define the total genetic component configuration (TGCC) (including chromosome, plasmid, and phage) for describing a strain as a systematic unit, the universal genome fingerprint map (UGFM) of TGCC for differentiating strains as a universal system, and the systematic comparative genomics (SCG) for comparing a set of genomes crossing genetic components and biological categories. Third, we construct a method of quantitative analysis to compare two genomes by using the outcome dataset of genome fingerprint analysis. Specifically, we define the geometric center and its geometric mean for a given genome fingerprint map, followed by the Euclidean distance, the differentiate rate, and the weighted differentiate rate to quantitatively describe the difference between two genomes of comparison. Moreover, we demonstrate the applications through case studies on various genome sequences, giving tremendous insights into the critical issues in microbial genomics and taxonomy. CONCLUSIONS: We have created a method, GenomeFingerprinter, for rapidly computing, geometrically visualizing, intuitively comparing a set of genomes at genome fingerprint level, and hence established a method called the universal genome fingerprint analysis, as well as developed a method of quantitative analysis of the outcome dataset. These have set up the methodology of systematic comparative genomics based on the genome fingerprint analysis.",2013 Oct 29,"['Ai, Yuncan', 'Ai, Hannan', 'Meng, Fanmei', 'Zhao, Lei']",PLoS One,,,True
1dad67bd586092707fb9e7d311d465b82b85425f,PMC,Infectious Bronchitis Virus Generates Spherules from Zippered Endoplasmic Reticulum Membranes,http://dx.doi.org/10.1128/mBio.00801-13,PMC3812713,24149513,CC BY,"Replication of positive-sense RNA viruses is associated with the rearrangement of cellular membranes. Previous work on the infection of tissue culture cell lines with the betacoronaviruses mouse hepatitis virus and severe acute respiratory syndrome coronavirus (SARS-CoV) showed that they generate double-membrane vesicles (DMVs) and convoluted membranes as part of a reticular membrane network. Here we describe a detailed study of the membrane rearrangements induced by the avian gammacoronavirus infectious bronchitis virus (IBV) in a mammalian cell line but also in primary avian cells and in epithelial cells of ex vivo tracheal organ cultures. In all cell types, structures novel to IBV infection were identified that we have termed zippered endoplasmic reticulum (ER) and spherules. Zippered ER lacked luminal space, suggesting zippering of ER cisternae, while spherules appeared as uniform invaginations of zippered ER. Electron tomography showed that IBV-induced spherules are tethered to the zippered ER and that there is a channel connecting the interior of the spherule with the cytoplasm, a feature thought to be necessary for sites of RNA synthesis but not seen previously for membrane rearrangements induced by coronaviruses. We also identified DMVs in IBV-infected cells that were observed as single individual DMVs or were connected to the ER via their outer membrane but not to the zippered ER. Interestingly, IBV-induced spherules strongly resemble confirmed sites of RNA synthesis for alphaviruses, nodaviruses, and bromoviruses, which may indicate similar strategies of IBV and these diverse viruses for the assembly of RNA replication complexes. IMPORTANCE All positive-sense single-stranded RNA viruses induce rearranged cellular membranes, providing a platform for viral replication complex assembly and protecting viral RNA from cellular defenses. We have studied the membrane rearrangements induced by an important poultry pathogen, the gammacoronavirus infectious bronchitis virus (IBV). Previous work studying closely related betacoronaviruses identified double-membrane vesicles (DMVs) and convoluted membranes (CMs) derived from the endoplasmic reticulum (ER) in infected cells. However, the role of DMVs and CMs in viral RNA synthesis remains unclear because these sealed vesicles lack a means of delivering viral RNA to the cytoplasm. Here, we characterized structures novel to IBV infection: zippered ER and small vesicles tethered to the zippered ER termed spherules. Significantly, spherules contain a channel connecting their interior to the cytoplasm and strongly resemble confirmed sites of RNA synthesis for other positive-sense RNA viruses, making them ideal candidates for the site of IBV RNA synthesis.",2013 Oct 22,"['Maier, Helena J.', 'Hawes, Philippa C.', 'Cottam, Eleanor M.', 'Mantell, Judith', 'Verkade, Paul', 'Monaghan, Paul', 'Wileman, Tom', 'Britton, Paul']",mBio,,,True
bdfce208ef62424bc68fdb610364dab6416365e1,PMC,Physiological Level Production of Antigen-Specific Human Immunoglobulin in Cloned Transchromosomic Cattle,http://dx.doi.org/10.1371/journal.pone.0078119,PMC3813428,24205120,CC BY,"Therapeutic human polyclonal antibodies (hpAbs) derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH) and kappa-chain (hIGK) germline loci (named as κHAC) are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO). However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM) and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ) in the pre-B cell receptor (pre-BCR) complex, we partially replaced (bovinized) the hIgM constant domain with the counterpart of bovine IgM (bIgM) that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO), the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype) in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG) can be produced from such Tc cattle.",2013 Oct 24,"['Sano, Akiko', 'Matsushita, Hiroaki', 'Wu, Hua', 'Jiao, Jin-An', 'Kasinathan, Poothappillai', 'Sullivan, Eddie J.', 'Wang, Zhongde', 'Kuroiwa, Yoshimi']",PLoS One,,,True
b59f1ed9272403216c276badc217b78b39251098,PMC,Defective Viral Genomes Arising In Vivo Provide Critical Danger Signals for the Triggering of Lung Antiviral Immunity,http://dx.doi.org/10.1371/journal.ppat.1003703,PMC3814336,24204261,CC BY,"The innate immune response to viruses is initiated when specialized cellular sensors recognize viral danger signals. Here we show that truncated forms of viral genomes that accumulate in infected cells potently trigger the sustained activation of the transcription factors IRF3 and NF-κB and the production type I IFNs through a mechanism independent of IFN signaling. We demonstrate that these defective viral genomes (DVGs) are generated naturally during respiratory infections in vivo even in mice lacking the type I IFN receptor, and their appearance coincides with the production of cytokines during infections with Sendai virus (SeV) or influenza virus. Remarkably, the hallmark antiviral cytokine IFNβ is only expressed in lung epithelial cells containing DVGs, while cells within the lung that contain standard viral genomes alone do not express this cytokine. Together, our data indicate that DVGs generated during viral replication are a primary source of danger signals for the initiation of the host immune response to infection.",2013 Oct 31,"['Tapia, Karla', 'Kim, Won-keun', 'Sun, Yan', 'Mercado-López, Xiomara', 'Dunay, Emily', 'Wise, Megan', 'Adu, Michael', 'López, Carolina B.']",PLoS Pathog,,,True
63dda1b262c68b84a8058a50480f0d5ae1b4f2ae,PMC,Identification of Novel Compounds Inhibiting Chikungunya Virus-Induced Cell Death by High Throughput Screening of a Kinase Inhibitor Library,http://dx.doi.org/10.1371/journal.pntd.0002471,PMC3814572,24205414,CC BY,"Chikungunya virus (CHIKV) is a mosquito-borne arthrogenic alphavirus that causes acute febrile illness in humans accompanied by joint pains and in many cases, persistent arthralgia lasting weeks to years. The re-emergence of CHIKV has resulted in numerous outbreaks in the eastern hemisphere, and threatens to expand in the foreseeable future. Unfortunately, no effective treatment is currently available. The present study reports the use of resazurin in a cell-based high-throughput assay, and an image-based high-content assay to identify and characterize inhibitors of CHIKV-infection in vitro. CHIKV is a highly cytopathic virus that rapidly kills infected cells. Thus, cell viability of HuH-7 cells infected with CHIKV in the presence of compounds was determined by measuring metabolic reduction of resazurin to identify inhibitors of CHIKV-associated cell death. A kinase inhibitor library of 4,000 compounds was screened against CHIKV infection of HuH-7 cells using the resazurin reduction assay, and the cell toxicity was also measured in non-infected cells. Seventy-two compounds showing ≥50% inhibition property against CHIKV at 10 µM were selected as primary hits. Four compounds having a benzofuran core scaffold (CND0335, CND0364, CND0366 and CND0415), one pyrrolopyridine (CND0545) and one thiazol-carboxamide (CND3514) inhibited CHIKV-associated cell death in a dose-dependent manner, with EC(50) values between 2.2 µM and 7.1 µM. Based on image analysis, these 6 hit compounds did not inhibit CHIKV replication in the host cell. However, CHIKV-infected cells manifested less prominent apoptotic blebs typical of CHIKV cytopathic effect compared with the control infection. Moreover, treatment with these compounds reduced viral titers in the medium of CHIKV-infected cells by up to 100-fold. In conclusion, this cell-based high-throughput screening assay using resazurin, combined with the image-based high content assay approach identified compounds against CHIKV having a novel antiviral activity - inhibition of virus-induced CPE - likely by targeting kinases involved in apoptosis.",2013 Oct 31,"['Cruz, Deu John M.', 'Bonotto, Rafaela M.', 'Gomes, Rafael G. B.', 'da Silva, Camila T.', 'Taniguchi, Juliana B.', 'No, Joo Hwan', 'Lombardot, Benoit', 'Schwartz, Olivier', 'Hansen, Michael A. E.', 'Freitas-Junior, Lucio H.']",PLoS Negl Trop Dis,,,True
d3a753e3847b2c8524486ee213fb614c3c52d8c3,PMC,Diagnosis of West Nile Virus Human Infections: Overview and Proposal of Diagnostic Protocols Considering the Results of External Quality Assessment Studies,http://dx.doi.org/10.3390/v5102329,PMC3814591,24072061,CC BY,"West Nile virus, genus Flavivirus, is transmitted between birds and occasionally other animals by ornithophilic mosquitoes. This virus also infects humans causing asymptomatic infections in about 85% of cases and <1% of clinical cases progress to severe neuroinvasive disease. The virus also presents a threat since most infections remain unapparent. However, the virus contained in blood and organs from asymptomatically infected donors can be transmitted to recipients of these infectious tissues. This paper reviews the presently available methods to achieve the laboratory diagnosis of West Nile virus infections in humans, discussing the most prominent advantages and disadvantages of each in light of the results obtained during four different External Quality Assessment studies carried out by the European Network for ‘Imported’ Viral Diseases (ENIVD).",2013 Sep 25,"['Sambri, Vittorio', 'Capobianchi, Maria R.', 'Cavrini, Francesca', 'Charrel, Rémi', 'Donoso-Mantke, Olivier', 'Escadafal, Camille', 'Franco, Leticia', 'Gaibani, Paolo', 'Gould, Ernest A.', 'Niedrig, Matthias', 'Papa, Anna', 'Pierro, Anna', 'Rossini, Giada', 'Sanchini, Andrea', 'Tenorio, Antonio', 'Varani, Stefania', 'Vázquez, Ana', 'Vocale, Caterina', 'Zeller, Herve']",Viruses,,,True
7a0108c70d3af86c64911d951b82ec9b1bda2818,PMC,"Sequence Heterogeneity of the ORF3 Gene of Porcine Epidemic Diarrhea Viruses Field Samples in Fujian, China, 2010–2012",http://dx.doi.org/10.3390/v5102375,PMC3814593,24084234,CC BY,"Twenty-seven field samples that showed positive in PEDV detection were collected from different farms of Fujian province from 2010 to 2012. Their heterogeneity was investigated by analysis of the ORF3 gene because of its potential function as a representation of virulence. According to the results, six Fujian strains in Group 1 showed a different genotype with unique point mutations, which might be used in differentiation between PEDV groups and brought potential antigenic variation. P55 and five reference strains in Group 2 had a long length deletion, showing another genotype and might be involved in the variation of virulence. Phylogenetic analysis revealed that the collected Fujian strains were very distant from the vaccine development strain CV777, which might be the reason why the vaccine was inefficient to control the disease. The results can help to reconsider the strategy of PEDV vaccine management and prevent outbreaks of PEDV-induced diarrhea more efficiently.",2013 Sep 30,"['Chen, Xi', 'Zeng, Lili', 'Yang, Jinxian', 'Yu, Fusong', 'Ge, Junqing', 'Guo, Qing', 'Gao, Xindang', 'Song, Tieying']",Viruses,,,True
78c991a34ec87c73006a683cd641762d15597890,PMC,Detection and Molecular Diversity of Spike Gene of Porcine Epidemic Diarrhea Virus in China,http://dx.doi.org/10.3390/v5102601,PMC3814607,24153062,CC BY,"Since late 2010, porcine epidemic diarrhea virus (PEDV) has rapidly disseminated all over the China and caused considerable morbidity and high mortality (up to 100%) in neonatal piglets. 79.66% (141 of 177) pig farms in 29 provinces (excluding Tibet and Hainan, China) and 72.27% (417 of 577) samples were positive for PEDV confirmed by reverse transcription-polymerase chain reaction (RT-PCR). The full-length S genes of representative field strains were sequenced. 33 field strains share 93.5%–99.9% homologies with each other at the nucleotide sequence level and 92.3%–99.8% homologies with each other at the amino acids sequence level. Most field strains have nucleotide deletion and insertion regions, and show lower homologies (93.5%–94.2%) with Chinese classical strain CH/S, however higher homologies (97.1%–99.3%) with recent strain CHGD-1. The phylogenetic analysis showed there are classical strains and variants prevailing in pig herd in China. PEDV has a high detection rate in pig herds in China. Sequence analysis indicated the S genes of recent field strains have heterogeneity and the variants are predominant.",2013 Oct 22,"['Chen, Jianfei', 'Liu, Xiaozhen', 'Shi, Da', 'Shi, Hongyan', 'Zhang, Xin', 'Li, Changlong', 'Chi, Yanbin', 'Feng, Li']",Viruses,,,True
937c21d92c53102251dc79fb436701d149789d4d,PMC,Bats and Viruses: Friend or Foe?,http://dx.doi.org/10.1371/journal.ppat.1003651,PMC3814676,24204253,CC BY,,2013 Oct 31,"['Wynne, James W.', 'Wang, Lin-Fa']",PLoS Pathog,,,True
25742d7fc7e3a5dfd8af95c2dbc9731494d13e67,PMC,The use of oral recombinant feline interferon omega in two cats with type II diabetes mellitus and concurrent feline chronic gingivostomatitis syndrome,http://dx.doi.org/10.1186/2046-0481-66-19,PMC3816157,24153100,CC BY,"Feline Chronic Gingivostomatitis Syndrome (FCGS) is a common disease in clinical practice. Among the therapeutic options available, long-acting corticosteroids are frequently used due to their anti-inflammatory and immunosuppressive properties. Although they may improve the clinical symptoms, they can lead to a progressive form of the disease that becomes refractory to treatment. Furthermore, their direct relationship with type II diabetes mellitus (DM) is well known. Consequently, these drugs are controversial and not recommended for routine management of FCGS. Recombinant feline interferon-omega (rFeIFN-ω) is an immunomodulatory compound. Recently, its daily oral administration has been shown to be successful in treating refractory cases of FCGS. This case study describes two clinical cases of type II DM complicated by FCGS. Both animals were calicivirus positive and they had been previously treated with long-acting corticosteroids, which may have been the major cause of DM. The two cats were treated with glargine insulin (Lantus, starting dose 1 IU/cat twice daily (BID)), achieving remission 10 and 18 weeks later respectively. Considering the difficulty with control of FCGS in these animals, an oral daily dose of rFeIFN-ω was started as an alternative to long-acting corticosteroids. In both cats oral clinical signs gradually improved and 60 days after the start of therapy the owners reported a significant relief of pain during mastication. According to the authors’ knowledge, this is the first case report that describes the successful use of rFeIFN-ω in the management of FCGS in type II diabetic cats, in which long-acting corticosteroids are contraindicated.",2013 Oct 23,"['Leal, Rodolfo O', 'Gil, Solange', 'Brito, Maria TV', 'McGahie, David', 'Niza, Maria MRE', 'Tavares, Luís']",Ir Vet J,,,True
6460342e18e6d3fea8f62630e12b083d46a6eb99,PMC,EpiBasket: how e-commerce tools can improve epidemiological preparedness,http://dx.doi.org/10.3402/ehtj.v6i0.19748,PMC3816197,24183326,CC BY,"BACKGROUND: Should an emerging infectious disease outbreak or an environmental disaster occur, the collection of epidemiological data must start as soon as possible after the event's onset. Questionnaires are usually built de novo for each event, resulting in substantially delayed epidemiological responses that are detrimental to the understanding and control of the event considered. Moreover, the public health and/or academic institution databases constructed with responses to different questionnaires are usually difficult to merge, impairing necessary collaborations. We aimed to show that e-commerce concepts and software tools can be readily adapted to enable rapid collection of data after an infectious disease outbreak or environmental disaster. Here, the ‘customers’ are the epidemiologists, who fill their shopping ‘baskets’ with standardised questions. METHODS: For each epidemiological field, a catalogue of questions is constituted by identifying the relevant variables based on a review of the published literature on similar circumstances. Each question is tagged with information on its source papers. Epidemiologists can then tailor their own questionnaires by choosing appropriate questions from this catalogue. The software immediately provides them with ready-to-use forms and online questionnaires. All databases constituted by the different EpiBasket users are interoperable, because the corresponding questionnaires are derived from the same corpus of questions. RESULTS: A proof-of-concept prototype was developed for Knowledge, Attitudes and Practice (KAP) surveys, which is one of the fields of the epidemiological investigation frequently explored during, or after, an outbreak or environmental disaster. The catalogue of questions was initiated from a review of the KAP studies conducted during or after the 2003 severe acute respiratory syndrome epidemic. CONCLUSION: Rapid collection of standardised data after an outbreak or environmental disaster can be facilitated by transposing the e-commerce paradigm to epidemiology, taking advantage of the powerful software tools already available.",2013 Oct 31,"['Xing, Weijia', 'Hejblum, Gilles', 'Valleron, Alain-Jacques']",Emerg Health Threats J,,,True
0a11a6e99c61da77f540fa28b3ab843761537711,PMC,RNAi Therapeutic Platforms for Lung Diseases,http://dx.doi.org/10.3390/ph6020223,PMC3816685,24275949,CC BY,"RNA interference (RNAi) is rapidly becoming an important method for analyzing gene functions in many eukaryotes and holds promise for the development of therapeutic gene silencing. The induction of RNAi relies on small silencing RNAs, which affect specific messenger RNA (mRNA) degradation. Two types of small RNA molecules, i.e. small interfering RNAs (siRNAs) and microRNAs (miRNAs), are central to RNAi. Drug discovery studies and novel treatments of siRNAs are currently targeting a wide range of diseases, including various viral infections and cancers. Lung diseases in general are attractive targets for siRNA therapeutics because of their lethality and prevalence. In addition, the lung is anatomically accessible to therapeutic agents via the intrapulmonary route. Recently, increasing evidence indicates that miRNAs play an important role in lung abnormalities, such as inflammation and oncogenesis. Therefore, miRNAs are being targeted for therapeutic purposes. In this review, we present strategies for RNAi delivery and discuss the current state-of-the-art RNAi-based therapeutics for various lung diseases.",2013 Feb 6,"['Fujita, Yu', 'Takeshita, Fumitaka', 'Kuwano, Kazuyoshi', 'Ochiya, Takahiro']",Pharmaceuticals (Basel),,,True
ebf258ca8bfc0adbd09d0ebe0c5f25688fbc7c34,PMC,Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Epithelial Cells Are Less Tolerant to Infection by Staphylococcus aureus,http://dx.doi.org/10.1371/journal.pone.0079566,PMC3817128,24223971,CC BY,"Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway and provides reducing energy to all cells by maintaining redox balance. The most common clinical manifestations in patients with G6PD deficiency are neonatal jaundice and acute hemolytic anemia. The effects of microbial infection in patients with G6PD deficiency primarily relate to the hemolytic anemia caused by Plasmodium or viral infections and the subsequent medication that is required. We are interested in studying the impact of bacterial infection in G6PD-deficient cells. G6PD knock down A549 lung carcinoma cells, together with the common pathogen Staphylococcus aureus, were employed in our cell infection model. Here, we demonstrate that a lower cell viability was observed among G6PD-deficient cells when compared to scramble controls upon bacterial infection using the MTT assay. A significant increase in the intracellular ROS was detected among S. aureus-infected G6PD-deficient cells by observing dichlorofluorescein (DCF) intensity within cells under a fluorescence microscope and quantifying this signal using flow cytometry. The impairment of ROS removal is predicted to enhance apoptotic activity in G6PD-deficient cells, and this enhanced apoptosis was observed by annexin V/PI staining under a confocal fluorescence microscope and quantified by flow cytometry. A higher expression level of the intrinsic apoptotic initiator caspase-9, as well as the downstream effector caspase-3, was detected by Western blotting analysis of G6PD-deficient cells following bacterial infection. In conclusion, we propose that bacterial infection, perhaps the secreted S. aureus α-hemolysin in this case, promotes the accumulation of intracellular ROS in G6PD-deficient cells. This would trigger a stronger apoptotic activity through the intrinsic pathway thereby reducing cell viability when compared to wild type cells.",2013 Nov 4,"['Hsieh, Yi-Ting', 'Lin, Mei-Hui', 'Ho, Hung-Yao', 'Chen, Lei-Chin', 'Chen, Chien-Cheng', 'Shu, Jwu-Ching']",PLoS One,,,True
2d266d6c9ef81ffefa8fc5ba319851d220e71cbd,PMC,Autologous Antibody Capture to Enrich Immunogenic Viruses for Viral Discovery,http://dx.doi.org/10.1371/journal.pone.0078454,PMC3817278,24223808,CC BY,"Discovery of new viruses has been boosted by novel deep sequencing technologies. Currently, many viruses can be identified by sequencing without knowledge of the pathogenicity of the virus. However, attributing the presence of a virus in patient material to a disease in the patient can be a challenge. One approach to meet this challenge is identification of viral sequences based on enrichment by autologous patient antibody capture. This method facilitates identification of viruses that have provoked an immune response within the patient and may increase the sensitivity of the current virus discovery techniques. To demonstrate the utility of this method, virus discovery deep sequencing (VIDISCA-454) was performed on clinical samples from 19 patients: 13 with a known respiratory viral infection and 6 with a known gastrointestinal viral infection. Patient sera was collected from one to several months after the acute infection phase. Input and antibody capture material was sequenced and enrichment was assessed. In 18 of the 19 patients, viral reads from immunogenic viruses were enriched by antibody capture (ranging between 1.5x to 343x in respiratory material, and 1.4x to 53x in stool). Enriched reads were also determined in an identity independent manner by using a novel algorithm Xcompare. In 16 of the 19 patients, 21% to 100% of the enriched reads were derived from infecting viruses. In conclusion, the technique provides a novel approach to specifically identify immunogenic viral sequences among the bulk of sequences which are usually encountered during virus discovery metagenomics.",2013 Nov 4,"['Oude Munnink, Bas B.', 'Jazaeri Farsani, Seyed Mohammad', 'Deijs, Martin', 'Jonkers, Jiri', 'Verhoeven, Joost T. P.', 'Ieven, Margareta', 'Goossens, Herman', 'de Jong, Menno D.', 'Berkhout, Ben', 'Loens, Katherine', 'Kellam, Paul', 'Bakker, Margreet', 'Canuti, Marta', 'Cotten, Matthew', 'van der Hoek, Lia']",PLoS One,,,True
cf0d47062feee58725fffdbd8b91eec680237fc1,PMC,Targeting Antigens to Dendritic Cell Receptors for Vaccine Development,http://dx.doi.org/10.1155/2013/869718,PMC3817681,24228179,CC BY,"Dendritic cells (DCs) are highly specialized antigen presenting cells of the immune system which play a key role in regulating immune responses. Depending on the method of antigen delivery, DCs stimulate immune responses or induce tolerance. As a consequence of the dual function of DCs, DCs are studied in the context of immunotherapy for both cancer and autoimmune diseases. In vaccine development, a major aim is to induce strong, specific T-cell responses. This is achieved by targeting antigen to cell surface molecules on DCs that efficiently channel the antigen into endocytic compartments for loading onto MHC molecules and stimulation of T-cell responses. The most attractive cell surface receptors, expressed on DCs used as targets for antigen delivery for cancer and other diseases, are discussed.",2013 Oct 8,"['Apostolopoulos, Vasso', 'Thalhammer, Theresia', 'Tzakos, Andreas G.', 'Stojanovska, Lily']",J Drug Deliv,,,True
b5215808485ffba5aa16d95577bd6344ede9d45c,PMC,Viral IRES Prediction System - a Web Server for Prediction of the IRES Secondary Structure In Silico,http://dx.doi.org/10.1371/journal.pone.0079288,PMC3818432,24223923,CC BY,"The internal ribosomal entry site (IRES) functions as cap-independent translation initiation sites in eukaryotic cells. IRES elements have been applied as useful tools for bi-cistronic expression vectors. Current RNA structure prediction programs are unable to predict precisely the potential IRES element. We have designed a viral IRES prediction system (VIPS) to perform the IRES secondary structure prediction. In order to obtain better results for the IRES prediction, the VIPS can evaluate and predict for all four different groups of IRESs with a higher accuracy. RNA secondary structure prediction, comparison, and pseudoknot prediction programs were implemented to form the three-stage procedure for the VIPS. The backbone of VIPS includes: the RNAL fold program, aimed to predict local RNA secondary structures by minimum free energy method; the RNA Align program, intended to compare predicted structures; and pknotsRG program, used to calculate the pseudoknot structure. VIPS was evaluated by using UTR database, IRES database and Virus database, and the accuracy rate of VIPS was assessed as 98.53%, 90.80%, 82.36% and 80.41% for IRES groups 1, 2, 3, and 4, respectively. This advance useful search approach for IRES structures will facilitate IRES related studies. The VIPS on-line website service is available at http://140.135.61.250/vips/.",2013 Nov 5,"['Hong, Jun-Jie', 'Wu, Tzong-Yuan', 'Chang, Tsair-Yuan', 'Chen, Chung-Yung']",PLoS One,,,True
bc381e908d987cbecf5fb3df2640a7c878886405,PMC,Broad-Spectrum Detection of H5 Subtype Influenza A Viruses with a New Fluorescent Immunochromatography System,http://dx.doi.org/10.1371/journal.pone.0076753,PMC3819354,24223117,CC BY,"Immunochromatography (IC) is an antigen-detection assay that plays an important role in the rapid diagnosis of influenza virus because the protocol is short time and easy to use. Despite the usability of IC, the sensitivity is approximately 10(3) pfu per reaction. In addition, antigen-antibody interaction-based method cannot be used for the detection of influenza viruses with major antigenic change. In this study, we established the use of fluorescent immunochromatography (FLIC) to detect a broad spectrum of H5 subtype influenza A viruses. This method has improved sensitivity 10–100 fold higher than traditional IC because of the use of fluorescent conjugated beads. Our Type-E FLIC kit detected all of the H5 subtype influenza viruses that were examined, as well as recombinant hemagglutinin (HA) proteins (rHAs) belonging to the Eurasian H5 subtype viruses and the Type-N diagnosed North American H5 subtype influenza A viruses. Thus, this kit has the improved potential to detect H5 subtype influenza viruses of different clades with both Type-E and Type-N FLIC kits. Compared with PCR-based diagnosis, FLIC has a strong advantage in usability, because the sample preparation required for FLIC is only mix-and-drop without any additional steps such as RNA extraction. Our results can provide new strategies against the spread and transmission of HPAI H5N1 viruses in birds and mammals including humans.",2013 Nov 6,"['Sakurai, Akira', 'Takayama, Katsuyoshi', 'Nomura, Namiko', 'Munakata, Tsubasa', 'Yamamoto, Naoki', 'Tamura, Tsuruki', 'Yamada, Jitsuho', 'Hashimoto, Masako', 'Kuwahara, Kazuhiko', 'Sakoda, Yoshihiro', 'Suda, Yoshihiko', 'Kobayashi, Yukuharu', 'Sakaguchi, Nobuo', 'Kida, Hiroshi', 'Kohara, Michinori', 'Shibasaki, Futoshi']",PLoS One,,,True
1829dd66176c20fb22a9d7186d62fa596cc93f9c,PMC,Rhinovirus-Induced Exacerbations of Asthma and COPD,http://dx.doi.org/10.1155/2013/405876,PMC3820304,24278777,CC BY,"Over the past two decades, increasing evidence has shown that, in patients with chronic airways disease, viral infection is the most common cause of exacerbation. This review will examine the evidence for viral-induced exacerbations of asthma and chronic obstructive lung disease and the potential mechanisms by which viruses cause exacerbations. Attention will be focused on rhinovirus, the most common cause of respiratory exacerbations. Exacerbations due to rhinovirus, which infects relatively few cells in the airway and does not cause the cytotoxicity of other viruses such as influenza or respiratory syncytial virus, are particularly poorly understood. While the innate immune response likely plays a role in rhinovirus-induced exacerbations, its precise role, either adaptive or maladaptive, is debated. Because current treatment strategies are only partially effective, further research examining the cellular and molecular mechanisms underlying viral-induced exacerbations of chronic airways diseases is warranted.",2013 Feb 21,"Hershenson, Marc B.",Scientifica (Cairo),,,True
25eb6cba256ef7c1dce823fc897b29a642aa0d5c,PMC,"The Past, Present, and Future of Public Health Surveillance",http://dx.doi.org/10.6064/2012/875253,PMC3820481,24278752,CC BY,"This paper provides a review of the past, present, and future of public health surveillance—the ongoing systematic collection, analysis, interpretation, and dissemination of health data for the planning, implementation, and evaluation of public health action. Public health surveillance dates back to the first recorded epidemic in 3180 B.C. in Egypt. Hippocrates (460 B.C.–370 B.C.) coined the terms endemic and epidemic, John Graunt (1620–1674) introduced systematic data analysis, Samuel Pepys (1633–1703) started epidemic field investigation, William Farr (1807–1883) founded the modern concept of surveillance, John Snow (1813–1858) linked data to intervention, and Alexander Langmuir (1910–1993) gave the first comprehensive definition of surveillance. Current theories, principles, and practice of public health surveillance are summarized. A number of surveillance dichotomies, such as epidemiologic surveillance versus public health surveillance, are described. Some future scenarios are presented, while current activities that can affect the future are summarized: exploring new frontiers; enhancing computer technology; improving epidemic investigations; improving data collection, analysis, dissemination, and use; building on lessons from the past; building capacity; enhancing global surveillance. It is concluded that learning from the past, reflecting on the present, and planning for the future can further enhance public health surveillance.",2012 Aug 5,"Choi, Bernard C. K.",Scientifica (Cairo),,,True
27969ab6c34a3d9b630666d5876256a9641bc05a,PMC,How Do Viruses Avoid Inhibition by Endogenous Cellular MicroRNAs?,http://dx.doi.org/10.1371/journal.ppat.1003694,PMC3820716,24244153,CC BY,,2013 Nov 7,"Cullen, Bryan R.",PLoS Pathog,,,True
c8973a511fb65247ed8f08c777512f17d5c4e977,PMC,Serum proteomics analysis and comparisons using iTRAQ in the progression of hepatitis B,http://dx.doi.org/10.3892/etm.2013.1310,PMC3820766,24223640,CC BY,"The aim of this study was to analyze the changes in serum protein levels in the progression of hepatitis B using isobaric tags for relative and absolute quantitation (iTRAQ) analysis, in addition to comparing the serum protein levels of patients with chronic hepatitis B (CHB), patients with hepatitis B virus-induced acute-on-chronic liver failure (HBV-induced ACLF) and normal individuals. Protein analysis was performed on 15 serum samples using iTRAQ. The study population included healthy controls (n=5), patients with CHB (n=5) and patients with HBV-induced ACLF (n=5). Western blotting was used to verify the results in an additional nine serum samples from healthy controls, patients with CHB and patients with HBV-induced ACLF (n=3, respectively). Using iTRAQ analysis, 16 different serum proteins with ≥1.5-fold differences in expression levels were identified in the patients with CHB and ACLF compared with the healthy controls. Five of those proteins, C-reactive protein precursor, hemoglobin β chain variant Hb S-Wake, apolipoprotein J precursor, platelet factor 4 precursor and vitronectin, which demonstrated the greatest differences in their expression levels and the most significant correlation with liver diseases, were subsequently verified using western blotting. The western blotting results were consistent with the results from the iTRAQ. Two of the five proteins are not classified by biological process, and the biological functions of all the proteins in HBV-induced ACLF remain unclear. This preliminary study demonstrated that a correlation between the expression of various serum proteins and the different pathogenetic conditions induced by HBV may exist. The analysis of a larger number of samples is required to identify potential protein biomarkers that may be involved in the pathogenesis and progression of hepatitis B.",2013 Nov 18,"['PENG, LIANG', 'LIU, JING', 'LI, YANG-MEI', 'HUANG, ZHAN-LIAN', 'WANG, PEI-PEI', 'GU, YU-RONG', 'ZHENG, YU-BAO', 'GAO, ZHI-LIANG']",Exp Ther Med,,,True
17a425d3e66241ada9c347aa0e0387231be31dcd,PMC,"Yu Ping Feng San, an Ancient Chinese Herbal Decoction Containing Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, Regulates the Release of Cytokines in Murine Macrophages",http://dx.doi.org/10.1371/journal.pone.0078622,PMC3823765,24244327,CC BY,"Yu Ping Feng San (YPFS), a Chinese herbal decoction, is composed of Astragali Radix (AR; Huangqi), Atractylodis Macrocephalae Rhizoma (AMR; Baizhu) and Saposhnikoviae Radix (SR; Fangfeng) in a weight ratio of 1∶2∶1. Clinically, YPFS has been widely used to regulate immune functions; however, the action mechanism of it is not known. Here, we addressed this issue by providing detail analyses of chemical and biological properties of YPFS. By using rapid resolution liquid chromatography coupled with mass spectrometry, fifteen chemicals deriving from different herbs of YPFS were determined, and which served as a control for the standardization of the herbal extract of YPFS. In general, the amounts of chosen chemical markers were higher in a preparation of YPFS as compared to that of single herb or two-herb compositions. In order to reveal the immune functions of YPFS, the standardized extract was applied onto cultured murine macrophages. The treatment of YPFS stimulated the mRNA and protein expressions of pro-inflammatory cytokines via activation of NF-κB by enhancing IκBα degradation. In contrast, the application of YPFS suppressed the expressions of pro-inflammatory cytokines significantly in the lipopolysaccharide (LPS)-induced chronic inflammation model. In addition, YPFS could up regulate the phagocytic activity in cultured macrophages. These results therefore supported the bi-directional immune-modulatory roles of YPFS in regulating the releases of cytokines from macrophages.",2013 Nov 11,"['Du, Crystal Y. Q.', 'Choi, Roy C. Y.', 'Zheng, Ken Y. Z.', 'Dong, Tina T. X.', 'Lau, David T. W.', 'Tsim, Karl W. K.']",PLoS One,,,True
580ef02f408295bba21f0ad87b6eba6ba9676163,PMC,Traditional Chinese Medicine Diagnosis “Yang-Xu Zheng”: Significant Prognostic Predictor for Patients with Severe Sepsis and Septic Shock,http://dx.doi.org/10.1155/2013/759748,PMC3824639,24282436,CC BY,"Pathogenesis of sepsis includes complex interaction between pathogen activities and host response, manifesting highly variable signs and symptoms, possibly delaying diagnosis and timely life-saving interventions. This study applies traditional Chinese medicine (TCM) Zheng diagnosis in patients with severe sepsis and septic shock to evaluate its adaptability and use as an early predictor of sepsis mortality. Three-year prospective observational study enrolled 126 septic patients. TCM Zheng diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and blood samples for host response cytokines measurement (tumor necrosis factor-α, Interleukin-6, Interleukin-8, Interleukin-10, Interleukin-18) were collected within 24 hours after admission to Intensive Care Unit. Main outcome was 28-day mortality; multivariate logistic regression analysis served to determine predictive variables of the sepsis mortality. APACHE II score, frequency of Nutrient-phase heat, and Qi-Xu and Yang-Xu Zhengs were significantly higher in nonsurvivors. The multivariate logistic regression analysis identified Yang-Xu Zheng as the outcome predictor. APACHE II score and levels of five host response cytokines between patients with and without Yang-Xu Zheng revealed significant differences. Furthermore, cool extremities and weak pulse, both diagnostic signs of Yang-Xu Zheng, were also proven independent predictors of sepsis mortality. TCM diagnosis “Yang-Xu Zheng” may provide a new mortality predictor for septic patients.",2013 Oct 24,"['Lin, Sunny Jui-Shan', 'Cheng, Yung-Yen', 'Chang, Chih-Hung', 'Lee, Cheng-Hung', 'Huang, Yi-Chia', 'Su, Yi-Chang']",Evid Based Complement Alternat Med,,,True
0807d06a6db06216d0b9399f4658a4ffb581db03,PMC,Defects in Base Excision Repair Sensitize Cells to Manganese in S. cerevisiae,http://dx.doi.org/10.1155/2013/295635,PMC3825218,24282812,CC BY,"Manganese (Mn) is essential for normal physiologic functioning; therefore, deficiencies and excess intake of manganese can result in disease. In humans, prolonged exposure to manganese causes neurotoxicity characterized by Parkinson-like symptoms. Mn(2+) has been shown to mediate DNA damage possibly through the generation of reactive oxygen species. In a recent publication, we showed that Mn induced oxidative DNA damage and caused lesions in thymines. This study further investigates the mechanisms by which cells process Mn(2+)-mediated DNA damage using the yeast S. cerevisiae. The strains most sensitive to Mn(2+) were those defective in base excision repair, glutathione synthesis, and superoxide dismutase mutants. Mn(2+) caused a dose-dependent increase in the accumulation of mutations using the CAN1 and lys2-10A mutator assays. The spectrum of CAN1 mutants indicates that exposure to Mn results in accumulation of base substitutions and frameshift mutations. The sensitivity of cells to Mn(2+) as well as its mutagenic effect was reduced by N-acetylcysteine, glutathione, and Mg(2+). These data suggest that Mn(2+) causes oxidative DNA damage that requires base excision repair for processing and that Mn interferes with polymerase fidelity. The status of base excision repair may provide a biomarker for the sensitivity of individuals to manganese.",2013 Oct 27,"['Stephenson, Adrienne P.', 'Mazu, Tryphon K.', 'Miles, Jana S.', 'Freeman, Miles D.', 'Reams, R. Renee', 'Flores-Rozas, Hernan']",Biomed Res Int,,,True
c08002cc1b2282d646514bf4f2abde54ac144994,PMC,Recombinant lentogenic Newcastle disease virus expressing Ebola virus GP infects cells independently of exogenous trypsin and uses macropinocytosis as the major pathway for cell entry,http://dx.doi.org/10.1186/1743-422X-10-331,PMC3826533,24209904,CC BY,"BACKGROUND: Using reverse genetics, we generated a recombinant low-pathogenic LaSota strain Newcastle disease virus (NDV) expressing the glycoprotein (GP) of Ebola virus (EBOV), designated rLa-EBOVGP, and evaluated its biological characteristic in vivo and in vitro. RESULTS: The introduction and expression of the EBOV GP gene did not increase the virulence of the NDV vector in poultry or mice. EBOV GP was incorporated into the particle of the vector virus and the recombinant virus rLa-EBOVGP infected cells and spread within them independently of exogenous trypsin. rLa-EBOVGP is more resistant to NDV antiserum than the vector NDV and is moderately sensitive to EBOV GP antiserum. More importantly, infection with rLa-EBOVGP was markedly inhibited by IPA3, indicating that rLa-EBOVGP uses macropinocytosis as the major internalization pathway for cell entry. CONCLUSIONS: The results demonstrate that EBOV GP in recombinant NDV particles functions independently to mediate the viral infection of the host cells and alters the cell-entry pathway.",2013 Nov 9,"['Wen, Zhiyuan', 'Zhao, Bolin', 'Song, Kun', 'Hu, Xule', 'Chen, Weiye', 'Kong, Dongni', 'Ge, Jinying', 'Bu, Zhigao']",Virol J,,,True
cfafca2d4a79e684fdd5291ae3b69245ff13b61c,PMC,Public Health Response Systems In-Action: Learning from Local Health Departments’ Experiences with Acute and Emergency Incidents,http://dx.doi.org/10.1371/journal.pone.0079457,PMC3827361,24236137,CC BY,"As part of their core mission, public health agencies attend to a wide range of disease and health threats, including those that require routine, acute, and emergency responses. While each incident is unique, the number and type of response activities are finite; therefore, through comparative analysis, we can learn about commonalities in the response patterns that could improve predictions and expectations regarding the resources and capabilities required to respond to future acute events. In this study, we interviewed representatives from more than 120 local health departments regarding their recent experiences with real-world acute public health incidents, such as infectious disease outbreaks, severe weather events, chemical spills, and bioterrorism threats. We collected highly structured data on key aspects of the incident and the public health response, particularly focusing on the public health activities initiated and community partners engaged in the response efforts. As a result, we are able to make comparisons across event types, create response profiles, and identify functional and structural response patterns that have import for future public health preparedness and response. Our study contributes to clarifying the complexity of public health response systems and our analysis reveals the ways in which these systems are adaptive to the character of the threat, resulting in differential activation of functions and partners based on the type of incident. Continued and rigorous examination of the experiences of health departments throughout the nation will refine our very understanding of what the public health response system is, will enable the identification of organizational and event inputs to performance, and will allow for the construction of rich, relevant, and practical models of response operations that can be employed to strengthen public health systems.",2013 Nov 13,"['Hunter, Jennifer C.', 'Yang, Jane E.', 'Crawley, Adam W.', 'Biesiadecki, Laura', 'Aragón, Tomás J.']",PLoS One,,,True
00fcc6277c19f6b180232d7a6fe0b0abfafb21f7,PMC,Clinical Features and Factors Associated with Severity and Fatality among Patients with Severe Fever with Thrombocytopenia Syndrome Bunyavirus Infection in Northeast China,http://dx.doi.org/10.1371/journal.pone.0080802,PMC3827460,24236203,CC BY,"BACKGROUND: In 2009, severe fever with thrombocytopenia syndrome virus (SFTSV) was identified as a novel member of the genus phlebovirus in the Bunyaviridae family in China. The detailed clinical features of cases with SFTSV infection have not been well described, and the risk factors for severity among patients and fatality among severe patients remain to be determined. METHODOLOGY/PRINCIPAL FINDINGS: Clinical and laboratory features of 115 hospitalized patients with SFTSV infection during the period from June 2010 to December 2011 in Northeast China were retrospectively reviewed. We assessed the risk factors associated with severity in confirmed cases and fatality in severe cases by multivariate analysis. One hundred and three (89.6%) of 115 patients presented with multiple organ dysfunction, and 22 (19.1%) of 115 proceeded to the stage of life threatening multiple organ failure. Of the 115 patients, 14 fatalities (12.2%) were reported. Multivariate analysis demonstrated that the independent predictors of risk for severity were: albumin ≤30 g/l (OR, 8.09; 95% CI, 2.58-25.32), APTT ≥ 66 seconds (OR, 14.28; 95% CI, 3.28-62.24), sodium ≤130 mmol/l (OR, 5.44; 95% CI, 1.38-21.40), and presence of neurological manifestations (OR, 7.70; 95% CI, 1.91-31.12). Among patients with severe disease, presence of acute lung injury/acute respiratory distress syndrome (HR, 4.59; 95% CI, 1.48–14.19) and disseminated intravascular coagulation (HR, 4.24; 95% CI, 1.38–13.03) were independently associated with fatality. CONCLUSIONS/SIGNIFICANCE: SFTSV infection may present with more severe symptoms and laboratory abnormalities than hitherto reported. Due to infection with a novel bunyavirus, the patients may sufferer multiple organ dysfunction and die of multiple organ failure. In the clinical assessment of any case of SFTS, independent factors relating to prognosis need to be taken into account by clinicians.",2013 Nov 13,"['Deng, Baocheng', 'Zhou, Bo', 'Zhang, Shujun', 'Zhu, Ying', 'Han, Leqiang', 'Geng, Yingzhi', 'Jin, Zhenan', 'Liu, Hongbo', 'Wang, Donglei', 'Zhao, Yitong', 'Wen, Ying', 'Cui, Wei', 'Zhou, Ying', 'Gu, Qiuhong', 'Sun, Cuiming', 'Lu, Xu', 'Wang, Wen', 'Wang, Yu', 'Li, Chengbo', 'Wang, Yanli', 'Yao, Wenqing', 'Liu, Pei']",PLoS One,,,True
4f5a550869a4ff5f8c754a9aa89453486cab2985,PMC,Limited Promiscuity of HLA-DRB1 Presented Peptides Derived of Blood Coagulation Factor VIII,http://dx.doi.org/10.1371/journal.pone.0080239,PMC3828219,24244658,CC BY,"The formation of inhibitory antibodies directed against coagulation factor VIII (FVIII) is a severe complication in the treatment of hemophilia A patients. The induction of anti-FVIII antibodies is a CD4(+) T cell-dependent process. Activation of FVIII-specific CD4(+) T cells is dependent on the presentation of FVIII-derived peptides on MHC class II by antigen-presenting cells. Previously, we have shown that FVIII-pulsed human monocyte-derived dendritic cells can present peptides from several FVIII domains. In this study we show that FVIII peptides are presented on immature as well as mature dendritic cells. In immature dendritic cells half of the FVIII-loaded MHC class II molecules are retained within the cell, whereas in LPS-matured dendritic cells the majority of MHC class II/peptide complexes is present on the plasma membrane. Time-course studies revealed that presentation of FVIII-derived peptides was optimal between 12 and 24 hours after maturation but persisted for at least 96 hours. We also show that macrophages are able to internalize FVIII as efficiently as dendritic cells, however FVIII was presented on MHC class II with a lower efficiency and with different epitopes compared to dendritic cells. In total, 48 FVIII core-peptides were identified using a DCs derived of 8 different donors. Five HLA-promiscuous FVIII peptide regions were found – these were presented by at least 4 out of 8 donors. The remaining 42 peptide core regions in FVIII were presented by DCs derived from a single (30 peptides) or two to three donors (12 peptides). Overall, our findings show that a broad repertoire of FVIII peptides can be presented on HLA-DR.",2013 Nov 14,"['van Haren, Simon D.', 'Wroblewska, Aleksandra', 'Herczenik, Eszter', 'Kaijen, Paul H.', 'Ruminska, Aleksandra', 'ten Brinke, Anja', 'Meijer, Alexander B.', 'Voorberg, Jan']",PLoS One,,,True
691bcdc9ee856e121db71833a0c56c43c3c25555,PMC,Limited Promiscuity of HLA-DRB1 Presented Peptides Derived of Blood Coagulation Factor VIII,http://dx.doi.org/10.1371/journal.pone.0080239,PMC3828219,24244658,CC BY,"The formation of inhibitory antibodies directed against coagulation factor VIII (FVIII) is a severe complication in the treatment of hemophilia A patients. The induction of anti-FVIII antibodies is a CD4(+) T cell-dependent process. Activation of FVIII-specific CD4(+) T cells is dependent on the presentation of FVIII-derived peptides on MHC class II by antigen-presenting cells. Previously, we have shown that FVIII-pulsed human monocyte-derived dendritic cells can present peptides from several FVIII domains. In this study we show that FVIII peptides are presented on immature as well as mature dendritic cells. In immature dendritic cells half of the FVIII-loaded MHC class II molecules are retained within the cell, whereas in LPS-matured dendritic cells the majority of MHC class II/peptide complexes is present on the plasma membrane. Time-course studies revealed that presentation of FVIII-derived peptides was optimal between 12 and 24 hours after maturation but persisted for at least 96 hours. We also show that macrophages are able to internalize FVIII as efficiently as dendritic cells, however FVIII was presented on MHC class II with a lower efficiency and with different epitopes compared to dendritic cells. In total, 48 FVIII core-peptides were identified using a DCs derived of 8 different donors. Five HLA-promiscuous FVIII peptide regions were found – these were presented by at least 4 out of 8 donors. The remaining 42 peptide core regions in FVIII were presented by DCs derived from a single (30 peptides) or two to three donors (12 peptides). Overall, our findings show that a broad repertoire of FVIII peptides can be presented on HLA-DR.",2013 Nov 14,"['van Haren, Simon D.', 'Wroblewska, Aleksandra', 'Herczenik, Eszter', 'Kaijen, Paul H.', 'Ruminska, Aleksandra', 'ten Brinke, Anja', 'Meijer, Alexander B.', 'Voorberg, Jan']",PLoS One,,,False
d4b76917de146cdbe4c922c15ac3d87d3d483446,PMC,Transcriptional profiling of feline infectious peritonitis virus infection in CRFK cells and in PBMCs from FIP diagnosed cats,http://dx.doi.org/10.1186/1743-422X-10-329,PMC3829811,24209771,CC BY,"BACKGROUND: Feline Infectious Peritonitis (FIP) is a lethal systemic disease, caused by the FIP Virus (FIPV); a virulent mutant of Feline Enteric Coronavirus (FECV). Currently, the viruses virulence determinants and host gene expressions during FIPV infection are not fully understood. METHODS: RNA sequencing of Crandell Rees Feline Kidney (CRFK) cells, infected with FIPV strain 79–1146 at 3 hours post infection (h.p.i), were sequenced using the Illumina next generation sequencing approach. Bioinformatic’s analysis, based on Felis catus 2X annotated shotgun reference genome, using CLC bio Genome Workbench mapped both control and infected cell reads to 18899 genes out of 19046 annotated genes. Kal’s Z test statistical analysis was used to analyse the differentially expressed genes from the infected CRFK cells. Real time RT-qPCR was developed for further transcriptional profiling of three genes (PD-1, PD-L1 and A3H) in infected CRFK cells and Peripheral Blood Mononuclear Cells (PBMCs) from healthy and FIP-diseased cats. RESULTS: Based on Kal’s Z-test, with False Discovery Rate (FDR) <0.05 and >1.99 fold change on gene expressions, a total of 61 genes were differentially expressed by both samples, where 44 genes were up-regulated and the remainder were down-regulated. Most genes were closely clustered together, suggesting a homogeneous expression. The majority of the genes that were significantly regulated, were those associated with monocytes-macrophage and Th1 cell functions, and the regulation of apoptosis. Real time RT-qPCR developed focusing on 2 up-regulated genes (PD-L1 and A3H) together with an apoptosis associated gene PD-1 expressions in FIPV infected CRFK cells and in PBMCs from healthy and FIP diagnosed cats produced concordant results with transcriptome data. CONCLUSION: The possible roles of these genes, and their importance in feline coronaviruses infection, are discussed.",2013 Nov 9,"['Harun, Mohammad Syamsul Reza', 'Kuan, Choong Oi', 'Selvarajah, Gayathri Thevi', 'Wei, Tan Sheau', 'Arshad, Siti Suri', 'Bejo, Mohd Hair', 'Omar, Abdul Rahman']",Virol J,,,True
28a0bf1e235fe876fff1127346bb3bac0b6e5072,PMC,Elucidating the Interacting Domains of Chandipura Virus Nucleocapsid Protein,http://dx.doi.org/10.1155/2013/594319,PMC3830837,24288532,CC BY,"The nucleocapsid (N) protein of Chandipura virus (CHPV) plays a crucial role in viral life cycle, besides being an important structural component of the virion through proper organization of its interactions with other viral proteins. In a recent study, the authors had mapped the associations among CHPV proteins and shown that N protein interacts with four of the viral proteins: N, phosphoprotein (P), matrix protein (M), and glycoprotein (G). The present study aimed to distinguish the regions of CHPV N protein responsible for its interactions with other viral proteins. In this direction, we have generated the structure of CHPV N protein by homology modeling using SWISS-MODEL workspace and Accelrys Discovery Studio client 2.55 and mapped the domains of N protein using PiSQRD. The interactions of N protein fragments with other proteins were determined by ZDOCK rigid-body docking method and validated by yeast two-hybrid and ELISA. The study revealed a unique binding site, comprising of amino acids 1–30 at the N terminus of the nucleocapsid protein (N1) that is instrumental in its interactions with N, P, M, and G proteins. It was also observed that N2 associates with N and G proteins while N3 interacts with N, P, and M proteins.",2013 Oct 28,"['Kumar, Kapila', 'Rajasekharan, Sreejith', 'Gulati, Sahil', 'Rana, Jyoti', 'Gabrani, Reema', 'Jain, Chakresh K.', 'Gupta, Amita', 'Chaudhary, Vijay K.', 'Gupta, Sanjay']",Adv Virol,,,True
6531f45674dda196c08f5a81a18eeea88ee6bb55,PMC,Targeting Toll-Like Receptors: Promising Therapeutic Strategies for the Management of Sepsis-Associated Pathology and Infectious Diseases,http://dx.doi.org/10.3389/fimmu.2013.00387,PMC3831162,24302927,CC BY,"Toll-like receptors (TLRs) are pattern recognition receptors playing a fundamental role in sensing microbial invasion and initiating innate and adaptive immune responses. TLRs are also triggered by danger signals released by injured or stressed cells during sepsis. Here we focus on studies developing TLR agonists and antagonists for the treatment of infectious diseases and sepsis. Positioned at the cell surface, TLR4 is essential for sensing lipopolysaccharide of Gram-negative bacteria, TLR2 is involved in the recognition of a large panel of microbial ligands, while TLR5 recognizes flagellin. Endosomal TLR3, TLR7, TLR8, TLR9 are specialized in the sensing of nucleic acids produced notably during viral infections. TLR4 and TLR2 are favorite targets for developing anti-sepsis drugs, and antagonistic compounds have shown efficient protection from septic shock in pre-clinical models. Results from clinical trials evaluating anti-TLR4 and anti-TLR2 approaches are presented, discussing the challenges of study design in sepsis and future exploitation of these agents in infectious diseases. We also report results from studies suggesting that the TLR5 agonist flagellin may protect from infections of the gastrointestinal tract and that agonists of endosomal TLRs are very promising for treating chronic viral infections. Altogether, TLR-targeted therapies have a strong potential for prevention and intervention in infectious diseases, notably sepsis.",2013 Nov 18,"['Savva, Athina', 'Roger, Thierry']",Front Immunol,,,True
c52ffa67fea523c74bd0c0f45033183f403692ed,PMC,Lung progenitors from lambs can differentiate into specialized alveolar or bronchiolar epithelial cells,http://dx.doi.org/10.1186/1746-6148-9-224,PMC3831758,24206786,CC BY,"BACKGROUND: Airways progenitors may be involved in embryogenesis and lung repair. The characterization of these important populations may enable development of new therapeutics to treat acute or chronic lung disease. In this study, we aimed to establish the presence of bronchioloalveolar progenitors in ovine lungs and to characterize their potential to differentiate into specialized cells. RESULTS: Lung cells were studied using immunohistochemistry on frozen sections of the lung. Immunocytochemistry and flow cytometry were conducted on ex-vivo derived pulmonary cells. The bronchioloalveolar progenitors were identified by their co-expression of CCSP, SP-C and CD34. A minor population of CD34(pos)/SP-C(pos)/CCSP(pos) cells (0.33% ± 0.31) was present ex vivo in cell suspensions from dissociated lungs. Using CD34 magnetic positive-cell sorting, undifferentiated SP-C(pos)/CCSP(pos) cells were purified (>80%) and maintained in culture. Using synthetic media and various extracellular matrices, SP-C(pos)/CCSP(pos) cells differentiated into either club cells (formerly named Clara cells) or alveolar epithelial type-II cells. Furthermore, these ex vivo and in vitro derived bronchioloalveolar progenitors expressed NANOG, OCT4 and BMI1, specifically described in progenitors or stem cells, and during lung development. CONCLUSIONS: We report for the first time in a large animal the existence of bronchioloalveolar progenitors with dual differentiation potential and the expression of specialized genes. These newly described cell population in sheep could be implicated in regeneration of the lung following lesions or in development of diseases such as cancers.",2013 Nov 8,"['Archer, Fabienne', 'Abi-Rizk, Alain', 'Desloire, Sophie', 'Dolmazon, Christine', 'Gineys, Barbara', 'Guiguen, François', 'Cottin, Vincent', 'Mornex, Jean-François', 'Leroux, Caroline']",BMC Vet Res,,,True
324deb63a4686d7efc7c32b8e20bdc7e96e1fb7e,PMC,Effects of Space Flight on the Chemical Constituents and Anti-Inflammatory Activity of Licorice (Glycyrrhiza uralensis Fisch),,PMC3832146,24250485,CC BY,"Licorice, the oldest Chinese traditional medicine, is widely used in the treatment of human diseases. Due to the deficiency of wild resource, selecting and breeding becomes a key issue to expanding the supply of licorice. Spaceflight technology will become a new method for medicinal plants. The aim of this study was to investigate the effect of spaceflight on the components and anti-inflammatory activity in licorice. After flowing on a recoverable satellite for 18 days, licorice seeds were germinated and grown to maturity and the parallel ground-based seeds were also planted under the same conditions. The main components in licorice root were analyzed through HPLC. The contents of two components in spaceflight groups were higher than that of the ground control ones. Three acute inflammatory models including xylene-induced auricular edema, carrageenan-induced paw edema and acetic acid-induced vascular permeability were utilized to compare the anti-inflammatory activity of licorice pre and post spaceflight. The licorice extract showed the significant anti-inflammation activity. After the spaceflight, the pharmacological activity of licorice got higher than that of the ground control one. All of the models gained the tendency that the spaceflight group of species Hangjinqi had the strongest activity than other groups. The research provided the scientific data for a new breeding of medicinal plant through the spaceflight and indicated that the technology of space flight may be a new effective method for the breeding and cultivation of licorice.",2012 Spring,"['Zhang, Jingze', 'Gao, Wenyuan', 'Yan, Shuo', 'Zhao, Yaxin']",Iran J Pharm Res,,,True
810749401200c77f19d5a7950070e0c2d4d2629e,PMC,Ubiquitin-Specific Proteases 25 Negatively Regulates Virus-Induced Type I Interferon Signaling,http://dx.doi.org/10.1371/journal.pone.0080976,PMC3832446,24260525,CC BY,"Ubiquitination and deubiquitination have emerged as critical regulatory processes in the virus-triggered type I interferon (IFN) induction pathway. In this study, we carried out a targeted siRNA screen of 54 ubiquitin-specific proteases (USPs) and identified USP25 as a negative regulator of the virus-triggered type I IFN signaling pathway. Overexpression of USP25 inhibited virus-induced activation of IFN-β, interferon regulation factor 3 (IRF3) and nuclear factor-kappa B (NF-κB), as well as the phosphorylation of IRF3 and NF-κB subunit p65. Furthermore, Knockdown of USP25 potentiated virus-induced induction of the IFN-β. In addition, detailed analysis demonstrated that USP25 cleaved lysine 48- and lysine 63-linked polyubiquitin chains in vitro and in vivo, and its deubiquitinating enzyme (DUB) activity, were dependent on a cysteine residue (Cys178) and a histidine residue (His607). USP25 mutants lacking DUB activity lost the ability to block virus-induced type I IFN to some degree. Mechanistically, USP25 deubiquitinated retinoic acid-inducible gene I (RIG-I), tumornecrosis factor (TNF) receptor-associated factor 2 (TRAF2), and TRAF6 to inhibit RIG-I-like receptor-mediated IFN signaling. Our findings suggest that USP25 is a novel DUB negatively regulating virus-induced type I IFN production.",2013 Nov 18,"['Zhong, Huijuan', 'Wang, Dang', 'Fang, Liurong', 'Zhang, Huan', 'Luo, Rui', 'Shang, Min', 'Ouyang, Chao', 'Ouyang, Haiping', 'Chen, Huanchun', 'Xiao, Shaobo']",PLoS One,,,True
7274f439641a1f4dc180a94cafe9b69d37e60415,PMC,Novel Virus Discovery and Genome Reconstruction from Field RNA Samples Reveals Highly Divergent Viruses in Dipteran Hosts,http://dx.doi.org/10.1371/journal.pone.0080720,PMC3832450,24260463,CC BY,"We investigated whether small RNA (sRNA) sequenced from field-collected mosquitoes and chironomids (Diptera) can be used as a proxy signature of viral prevalence within a range of species and viral groups, using sRNAs sequenced from wild-caught specimens, to inform total RNA deep sequencing of samples of particular interest. Using this strategy, we sequenced from adult Anopheles maculipennis s.l. mosquitoes the apparently nearly complete genome of one previously undescribed virus related to chronic bee paralysis virus, and, from a pool of Ochlerotatus caspius and Oc. detritus mosquitoes, a nearly complete entomobirnavirus genome. We also reconstructed long sequences (1503-6557 nt) related to at least nine other viruses. Crucially, several of the sequences detected were reconstructed from host organisms highly divergent from those in which related viruses have been previously isolated or discovered. It is clear that viral transmission and maintenance cycles in nature are likely to be significantly more complex and taxonomically diverse than previously expected.",2013 Nov 18,"['Cook, Shelley', 'Chung, Betty Y.-W.', 'Bass, David', 'Moureau, Gregory', 'Tang, Shuoya', 'McAlister, Erica', 'Culverwell, C. Lorna', 'Glücksman, Edvard', 'Wang, Hui', 'Brown, T. David K.', 'Gould, Ernest A.', 'Harbach, Ralph E.', 'de Lamballerie, Xavier', 'Firth, Andrew E.']",PLoS One,,,True
6a54a1fdb5e1476e36b632b0fb061da5b3b69b5c,PMC,Prevalence of Herpes and Respiratory Viruses in Induced Sputum among Hospitalized Children with Non Typical Bacterial Community-Acquired Pneumonia,http://dx.doi.org/10.1371/journal.pone.0079477,PMC3832587,24260230,CC BY,"OBJECTIVE: Few comprehensive studies have searched for viruses in infants and young children with community-acquired pneumonia (CAP) in China. The aim of this study was to investigate the roles of human herpes viruses (HHVs) and other respiratory viruses in CAP not caused by typical bacterial infection and to determine their prevalence and clinical significance. METHODS: Induced sputum (IS) samples were collected from 354 hospitalised patients (infants, n = 205; children, n = 149) with respiratory illness (CAP or non-CAP) admitted to Wenling Hospital of China. We tested for HHVs and respiratory viruses using PCR-based assays. The epidemiological profiles were also analysed. RESULTS: High rate of virus detection (more than 98%) and co-infection (more than 80%) were found among IS samples from 354 hospitalised infants and children with respiratory illness in this study. Of 273 CAP samples tested, CMV (91.6%), HHV-6 (50.9%), RSV (37.4%), EBV (35.5%), HBoV (28.2%), HHV-7 (18.3%) and rhinovirus (17.2%) were the most commonly detected viruses. Of 81 non- CAP samples tested, CMV (63%), RSV (49.4%), HHV-6 (42%), EBV (24.7%), HHV-7 (13.6%) and HBoV (8.6%) were the dominant viruses detected. The prevalence of several viral agents (rhinovirus, bocavirus, adenovirus and CMV) among IS samples of CAP were significantly higher than that of non-CAP control group. We also found the prevalence of RSV coinfection with HHVs was also higher among CAP group than that of non-CAP control. CONCLUSIONS: With sensitive molecular detection techniques and IS samples, high rates of viral identification were achieved in infants and young children with respiratory illness in a rural area of China. The clinical significance of rhinovirus, bocavirus, adenovirus and HHV (especially CMV) infections should receive greater attention in future treatment and prevention studies of CAP in infants and children.",2013 Nov 18,"['Zhou, Weimin', 'Lin, Feng', 'Teng, Lingfang', 'Li, Hua', 'Hou, Jianyi', 'Tong, Rui', 'Zheng, Changhua', 'Lou, Yongliang', 'Tan, Wenjie']",PLoS One,,,True
41d0c75e25a257485a79211632b5c9ed93d4df14,PMC,The biodistribution of self-assembling protein nanoparticles shows they are promising vaccine platforms,http://dx.doi.org/10.1186/1477-3155-11-36,PMC3832906,24219600,CC BY,"BACKGROUND: Because of the need to limit side-effects, nanoparticles are increasingly being studied as drug-carrying and targeting tools. We have previously reported on a scheme to produce protein-based self-assembling nanoparticles that can act as antigen display platforms. Here we attempted to use the same system for cancer-targeting, making use of a C-terminal bombesin peptide that has high affinity for a receptor known to be overexpressed in certain tumors, as well as an N-terminal polyhistidine tag that can be used for radiolabeling with technetium tricarbonyl. RESULTS: In order to increase circulation time, we experimented with PEGylated and unPEGylated varities typo particle. We also tested the effect of incorporating different numbers of bombesins per nanoparticle. Biophysical characterization determined that all configurations assemble into regular particles with relatively monodisperse size distributions, having peaks of about 33 – 36 nm. The carbonyl method used for labeling produced approximately 80% labeled nanoparticles. In vitro, the nanoparticles showed high binding, both specific and non-specific, to PC-3 prostate cancer cells. In vivo, high uptake was observed for all nanoparticle types in the spleens of CD-1 nu/nu mice, decreasing significantly over the course of 24 hours. High uptake was also observed in the liver, while only low uptake was seen in both the pancreas and a tumor xenograft. CONCLUSIONS: The data suggest that the nanoparticles are non-specifically taken up by the reticuloendothelial system. Low uptake in the pancreas and tumor indicate that there is little or no specific targeting. PEGylation or increasing the amount of bombesins per nanoparticle did not significantly improve targeting. In particular, the uptake in the spleen, which is a primary organ of the immune system, highlights the potential of the nanoparticles as vaccine carriers. Also, the decrease in liver and spleen radioactivity with time implies that the nanoparticles are broken down and cleared. This is an important finding, as it shows that the nanoparticles can be safely used as a vaccine platform without the risk of prolonged side effects. Furthermore, it demonstrates that technetium carbonyl radiolabeling of our protein-based nanoparticles can be used to evaluate their pharmacokinetic properties in vivo.",2013 Nov 12,"['Yang, Yongkun', 'Neef, Tobias', 'Mittelholzer, Christian', 'Garcia Garayoa, Elisa', 'Bläuenstein, Peter', 'Schibli, Roger', 'Aebi, Ueli', 'Burkhard, Peter']",J Nanobiotechnology,,,True
2d2b70166db15be7908f748930e9c56a300e5851,PMC,"Twentieth anniversary of the European Union health mandate: taking stock of perceived achievements, failures and missed opportunities – a qualitative study",http://dx.doi.org/10.1186/1471-2458-13-1074,PMC3833669,24225055,CC BY,"BACKGROUND: The European Union (EU) health mandate was initially defined in the Maastricht Treaty in 1992. The twentieth anniversary of the Treaty offers a unique opportunity to take stock of EU health actions by giving an overview of influential public health related EU-level policy outputs and a summary of policy outputs or actions perceived as an achievement, a failure or a missed opportunity. METHODS: Semi-structured expert interviews (N = 20) were conducted focusing on EU-level actions that were relevant for health. Respondents were asked to name EU policies or actions that they perceived as an achievement, a failure or a missed opportunity. A directed content analysis approach was used to identify expert perceptions on achievements, failures and missed opportunities in the interviews. Additionally, a nominal group technique was applied to identify influential and public health relevant EU-level policy outputs. RESULTS: The ranking of influential policy outputs resulted in top positions of adjudications and legislations, agencies, European Commission (EC) programmes and strategies, official networks, cooperative structures and exchange efforts, the work on health determinants and uptake of scientific knowledge. The assessment of EU health policies as being an achievement, a failure or a missed opportunity was often characterized by diverging respondent views. Recurring topics that emerged were the Directorate General for Health and Consumers (DG SANCO), EU agencies, life style factors, internal market provisions as well as the EU Directive on patients’ rights in cross-border healthcare. Among these recurring topics, expert perceptions on the establishment of DG SANCO, EU public health agencies, and successes in tobacco control were dominated by aspects of achievements. The implementation status of the Health in All Policy approach was perceived as a missed opportunity. CONCLUSIONS: When comparing the emerging themes from the interviews conducted with the responsibilities defined in the EU health mandate, one can identify that these responsibilities were only partly fulfilled or acknowledged by the respondents. In general, the EU is a recognized public health player in Europe which over the past two decades, has begun to develop competencies in supporting, coordinating and supplementing member state health actions. However, the assurance of health protection in other European policies seems to require further development.",2013 Nov 14,"['Rosenkötter, Nicole', 'Clemens, Timo', 'Sørensen, Kristine', 'Brand, Helmut']",BMC Public Health,,,True
801aad4fa6fab8d6d0973eb4df2178454195e037,PMC,Spironolactone Attenuates Bleomycin-Induced Pulmonary Injury Partially via Modulating Mononuclear Phagocyte Phenotype Switching in Circulating and Alveolar Compartments,http://dx.doi.org/10.1371/journal.pone.0081090,PMC3834272,24260540,CC BY,"BACKGROUND: Recent experimental studies provide evidence indicating that manipulation of the mononuclear phagocyte phenotype could be a feasible approach to alter the severity and persistence of pulmonary injury and fibrosis. Mineralocorticoid receptor (MR) has been reported as a target to regulate macrophage polarization. The present work was designed to investigate the therapeutic potential of MR antagonism in bleomycin-induced acute lung injury and fibrosis. METHODOLOGY/PRINCIPAL FINDINGS: We first demonstrated the expression of MR in magnetic bead-purified Ly6G-/CD11b+ circulating monocytes and in alveolar macrophages harvested in bronchoalveolar lavage fluid (BALF) from C57BL/6 mice. Then, a pharmacological intervention study using spironolactone (20mg/kg/day by oral gavage) revealed that MR antagonism led to decreased inflammatory cell infiltration, cytokine production (downregulated monocyte chemoattractant protein-1, transforming growth factor β1, and interleukin-1β at mRNA and protein levels) and collagen deposition (decreased lung total hydroxyproline content and collagen positive area by Masson’ trichrome staining) in bleomycin treated (2.5mg/kg, via oropharyngeal instillation) male C57BL/6 mice. Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6C(hi) monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+) of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c-) remained unaffected by spironolactone during investigation. CONCLUSIONS/SIGNIFICANCE: The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching.",2013 Nov 19,"['Ji, Wen-Jie', 'Ma, Yong-Qiang', 'Zhou, Xin', 'Zhang, Yi-Dan', 'Lu, Rui-Yi', 'Guo, Zhao-Zeng', 'Sun, Hai-Ying', 'Hu, Dao-Chuan', 'Yang, Guo-Hong', 'Li, Yu-Ming', 'Wei, Lu-Qing']",PLoS One,,,True
1c8a0fb2f60c243f71d16d5fefb5b51d7978869e,PMC,Proteome and phosphoproteome analysis of honeybee (Apis mellifera) venom collected from electrical stimulation and manual extraction of the venom gland,http://dx.doi.org/10.1186/1471-2164-14-766,PMC3835400,24199871,CC BY,"BACKGROUND: Honeybee venom is a complicated defensive toxin that has a wide range of pharmacologically active compounds. Some of these compounds are useful for human therapeutics. There are two major forms of honeybee venom used in pharmacological applications: manually (or reservoir disrupting) extracted glandular venom (GV), and venom extracted through the use of electrical stimulation (ESV). A proteome comparison of these two venom forms and an understanding of the phosphorylation status of ESV, are still very limited. Here, the proteomes of GV and ESV were compared using both gel-based and gel-free proteomics approaches and the phosphoproteome of ESV was determined through the use of TiO(2) enrichment. RESULTS: Of the 43 proteins identified in GV, < 40% were venom toxins, and > 60% of the proteins were non-toxic proteins resulting from contamination by gland tissue damage during extraction and bee death. Of the 17 proteins identified in ESV, 14 proteins (>80%) were venom toxic proteins and most of them were found in higher abundance than in GV. Moreover, two novel proteins (dehydrogenase/reductase SDR family member 11-like and histone H2B.3-like) and three novel phosphorylation sites (icarapin (S43), phospholipase A-2 (T145), and apamin (T23)) were identified. CONCLUSIONS: Our data demonstrate that venom extracted manually is different from venom extracted using ESV, and these differences may be important in their use as pharmacological agents. ESV may be more efficient than GV as a potential pharmacological source because of its higher venom protein content, production efficiency, and without the need to kill honeybee. The three newly identified phosphorylated venom proteins in ESV may elicit a different immune response through the specific recognition of antigenic determinants. The two novel venom proteins extend our proteome coverage of honeybee venom.",2013 Nov 7,"['Li, Rongli', 'Zhang, Lan', 'Fang, Yu', 'Han, Bin', 'Lu, Xiaoshan', 'Zhou, Tiane', 'Feng, Mao', 'Li, Jianke']",BMC Genomics,,,True
d2597e291d5073395da85f2db0f523f01530a3f6,PMC,A Genome-Wide Analysis of RNA Pseudoknots That Stimulate Efficient −1 Ribosomal Frameshifting or Readthrough in Animal Viruses,http://dx.doi.org/10.1155/2013/984028,PMC3835772,24298557,CC BY,"Programmed −1 ribosomal frameshifting (PRF) and stop codon readthrough are two translational recoding mechanisms utilized by some RNA viruses to express their structural and enzymatic proteins at a defined ratio. Efficient recoding usually requires an RNA pseudoknot located several nucleotides downstream from the recoding site. To assess the strategic importance of the recoding pseudoknots, we have carried out a large scale genome-wide analysis in which we used an in-house developed program to detect all possible H-type pseudoknots within the genomic mRNAs of 81 animal viruses. Pseudoknots are detected downstream from ~85% of the recoding sites, including many previously unknown pseudoknots. ~78% of the recoding pseudoknots are the most stable pseudoknot within the viral genomes. However, they are not as strong as some designed pseudoknots that exhibit roadblocking effect on the translating ribosome. Strong roadblocking pseudoknots are not detected within the viral genomes. These results indicate that the decoding pseudoknots have evolved to possess optimal stability for efficient recoding. We also found that the sequence at the gag-pol frameshift junction of HIV1 harbors potential elaborated pseudoknots encompassing the frameshift site. A novel mechanism is proposed for possible involvement of the elaborated pseudoknots in the HIV1 PRF event.",2013 Nov 4,"['Huang, Xiaolan', 'Cheng, Qiang', 'Du, Zhihua']",Biomed Res Int,,,False
01b5ae0cce289ca9cdcebc4079f960e833cfbd79,PMC,A Genome-Wide Analysis of RNA Pseudoknots That Stimulate Efficient −1 Ribosomal Frameshifting or Readthrough in Animal Viruses,http://dx.doi.org/10.1155/2013/984028,PMC3835772,24298557,CC BY,"Programmed −1 ribosomal frameshifting (PRF) and stop codon readthrough are two translational recoding mechanisms utilized by some RNA viruses to express their structural and enzymatic proteins at a defined ratio. Efficient recoding usually requires an RNA pseudoknot located several nucleotides downstream from the recoding site. To assess the strategic importance of the recoding pseudoknots, we have carried out a large scale genome-wide analysis in which we used an in-house developed program to detect all possible H-type pseudoknots within the genomic mRNAs of 81 animal viruses. Pseudoknots are detected downstream from ~85% of the recoding sites, including many previously unknown pseudoknots. ~78% of the recoding pseudoknots are the most stable pseudoknot within the viral genomes. However, they are not as strong as some designed pseudoknots that exhibit roadblocking effect on the translating ribosome. Strong roadblocking pseudoknots are not detected within the viral genomes. These results indicate that the decoding pseudoknots have evolved to possess optimal stability for efficient recoding. We also found that the sequence at the gag-pol frameshift junction of HIV1 harbors potential elaborated pseudoknots encompassing the frameshift site. A novel mechanism is proposed for possible involvement of the elaborated pseudoknots in the HIV1 PRF event.",2013 Nov 4,"['Huang, Xiaolan', 'Cheng, Qiang', 'Du, Zhihua']",Biomed Res Int,,,True
7d38e11db887bf824a89621f65d384ef45e14955,PMC,Development and Evaluation of a SYBR Green-Based Real Time RT-PCR Assay for Detection of the Emerging Avian Influenza A (H7N9) Virus,http://dx.doi.org/10.1371/journal.pone.0080028,PMC3835827,24278234,CC BY,"Most recently a novel avian-origin influenza A (H7N9) virus emerged in China and has been associated with lots of human infection and fatal cases. Genetic analysis of the viral genome revealed that this reassortant virus might be better adapted to humans than other avian influenza viruses. Molecular diagnostic methods are thus urgently needed in public health laboratories. In this study, a SYBR green-based one-step real time reverse transcription-PCR (RT-PCR) was developed to detect the novel H7N9 virus. The primer pairs on the basis of the hemagglutinin and neuraminidase gene sequences of H7N9 viruses amplified subtype-specific fragments with Tm values of 80.77±0.06°C for H7 and 81.20±0.17°C for N9 respectively. The standard curves showed a dynamic linear range across 6 log units of RNA copy number (10(6) to 10(1) copies/ µl) with a detection limit of 10 copies per reaction for both H7 and N9 assays by using serial ten-fold diluted in-vitro transcribed viral RNA. In addition, no cross-reactivity was observed with seasonal H1N1, H1N1 pdm09, H3N2, H5N1 and H9N2 viruses as well as other human respiratory viruses. When the assay was further evaluated in H7N9 virus infected clinical samples, positive amplification signals were obtained in all of the specimens with the accordance between H7 and N9 assays. Therefore, the established SYBR green-based real time RT-PCR assay could provide a rapid, sensitive, specific and reliable alternative approach with lower costs for high throughput screening of suspected samples from humans, animals and environments in first line public health laboratories.",2013 Nov 20,"['Zhu, Zheng', 'Fan, Huan', 'Qi, Xian', 'Qi, Yuhua', 'Shi, Zhiyang', 'Wang, Hua', 'Cui, Lunbiao', 'Zhou, Minghao']",PLoS One,,,True
e5526afbb4d770dabb8c34da47c1267ee3342959,PMC,Ultra-Deep Sequencing of Intra-host Rabies Virus Populations during Cross-species Transmission,http://dx.doi.org/10.1371/journal.pntd.0002555,PMC3836733,24278493,CC0,"One of the hurdles to understanding the role of viral quasispecies in RNA virus cross-species transmission (CST) events is the need to analyze a densely sampled outbreak using deep sequencing in order to measure the amount of mutation occurring on a small time scale. In 2009, the California Department of Public Health reported a dramatic increase (350) in the number of gray foxes infected with a rabies virus variant for which striped skunks serve as a reservoir host in Humboldt County. To better understand the evolution of rabies, deep-sequencing was applied to 40 unpassaged rabies virus samples from the Humboldt outbreak. For each sample, approximately 11 kb of the 12 kb genome was amplified and sequenced using the Illumina platform. Average coverage was 17,448 and this allowed characterization of the rabies virus population present in each sample at unprecedented depths. Phylogenetic analysis of the consensus sequence data demonstrated that samples clustered according to date (1995 vs. 2009) and geographic location (northern vs. southern). A single amino acid change in the G protein distinguished a subset of northern foxes from a haplotype present in both foxes and skunks, suggesting this mutation may have played a role in the observed increased transmission among foxes in this region. Deep-sequencing data indicated that many genetic changes associated with the CST event occurred prior to 2009 since several nonsynonymous mutations that were present in the consensus sequences of skunk and fox rabies samples obtained from 20032010 were present at the sub-consensus level (as rare variants in the viral population) in skunk and fox samples from 1995. These results suggest that analysis of rare variants within a viral population may yield clues to ancestral genomes and identify rare variants that have the potential to be selected for if environment conditions change.",2013 Nov 21,"['Borucki, Monica K.', 'Chen-Harris, Haiyin', 'Lao, Victoria', 'Vanier, Gilda', 'Wadford, Debra A.', 'Messenger, Sharon', 'Allen, Jonathan E.']",PLoS Negl Trop Dis,,,True
5e0e39574ffd7d5f3dcdc97d0301507de50e5c54,PMC,The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells,http://dx.doi.org/10.1371/journal.ppat.1003776,PMC3836734,24278022,CC BY,"The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses mucosal surfaces to establish infection are unknown. Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated by antibody. We found that the combination of acidic pH and Env-specific IgG, including that from cervicovaginal and seminal fluids of HIV-1-infected individuals, augmented transcytosis across epithelial cells as much as 20-fold compared with Env-specific IgG at neutral pH or non-specific IgG at either pH. Enhanced transcytosis was observed with clinical HIV-1 isolates, including transmitted/founder strains, and was eliminated in Fc neonatal receptor (FcRn)-knockdown epithelial cells. Non-neutralizing antibodies allowed similar or less transcytosis than neutralizing antibodies. However, the ratio of total:infectious virus was higher for neutralizing antibodies, indicating that they allowed transcytosis while blocking infectivity of transcytosed virus. Immunocytochemistry revealed abundant FcRn expression in columnar epithelia lining the human endocervix and penile urethra. Acidity and Env-specific IgG enhance transcytosis of virus across epithelial cells via FcRn and could facilitate translocation of virus to susceptible target cells following sexual exposure.",2013 Nov 21,"['Gupta, Sandeep', 'Gach, Johannes S.', 'Becerra, Juan C.', 'Phan, Tran B.', 'Pudney, Jeffrey', 'Moldoveanu, Zina', 'Joseph, Sarah B.', 'Landucci, Gary', 'Supnet, Medalyn Jude', 'Ping, Li-Hua', 'Corti, Davide', 'Moldt, Brian', 'Hel, Zdenek', 'Lanzavecchia, Antonio', 'Ruprecht, Ruth M.', 'Burton, Dennis R.', 'Mestecky, Jiri', 'Anderson, Deborah J.', 'Forthal, Donald N.']",PLoS Pathog,,,True
31e1410cb8c22cfaae254381a16e88ec633086e4,PMC,Defining the Range of Pathogens Susceptible to Ifitm3 Restriction Using a Knockout Mouse Model,http://dx.doi.org/10.1371/journal.pone.0080723,PMC3836756,24278312,CC BY,"The interferon-inducible transmembrane (IFITM) family of proteins has been shown to restrict a broad range of viruses in vitro and in vivo by halting progress through the late endosomal pathway. Further, single nucleotide polymorphisms (SNPs) in its sequence have been linked with risk of developing severe influenza virus infections in humans. The number of viruses restricted by this host protein has continued to grow since it was first demonstrated as playing an antiviral role; all of which enter cells via the endosomal pathway. We therefore sought to test the limits of antimicrobial restriction by Ifitm3 using a knockout mouse model. We showed that Ifitm3 does not impact on the restriction or pathogenesis of bacterial (Salmonella typhimurium, Citrobacter rodentium, Mycobacterium tuberculosis) or protozoan (Plasmodium berghei) pathogens, despite in vitro evidence. However, Ifitm3 is capable of restricting respiratory syncytial virus (RSV) in vivo either through directly restricting RSV cell infection, or by exerting a previously uncharacterised function controlling disease pathogenesis. This represents the first demonstration of a virus that enters directly through the plasma membrane, without the need for the endosomal pathway, being restricted by the IFITM family; therefore further defining the role of these antiviral proteins.",2013 Nov 21,"['Everitt, Aaron R.', 'Clare, Simon', 'McDonald, Jacqueline U.', 'Kane, Leanne', 'Harcourt, Katherine', 'Ahras, Malika', 'Lall, Amar', 'Hale, Christine', 'Rodgers, Angela', 'Young, Douglas B.', 'Haque, Ashraful', 'Billker, Oliver', 'Tregoning, John S.', 'Dougan, Gordon', 'Kellam, Paul']",PLoS One,,,True
8613777458478918e5fd17250ca0dc7dcb92e259,PMC,Quantification of Hantaan Virus with a SYBR Green Ⅰ-Based One-Step qRT-PCR Assay,http://dx.doi.org/10.1371/journal.pone.0081525,PMC3836762,24278449,CC BY,"Hantaan virus (HTNV) is a major zoonotic pathogen that causes hemorrhagic fever with renal syndrome (HFRS) in Asia, especially in China. Shaanxi province, which is located in northwest of China, is one of the areas in China most severely afflicted with HFRS epidemics annually. This study aims to establish a quantitative RT-PCR (qRT-PCR) assay to detect HTNV both in cell culture and clinical serum samples. We established a SYBR Green Ⅰ-based one-step qRT-PCR assay that targets the S segment of the HTNV genome for rapid detection and quantification. The HTNV cRNA standards were constructed by in vitro transcription, and the copy numbers of the HTNV cRNA were quantified. Standard curve was generated by determining the mean cycle threshold (Ct) values versus 10-fold serial dilutions of the HTNV cRNA over a range of 1×10(8) to 1×10(3) copies/μl. The standard curve had a reaction efficiency of 102.1%, a correlation coefficient (R(2)) of 0.998, and a slope of -3.273. The coefficient of variation (CV) of the intra- and inter-assays ranged from 0.68% to 3.00% and from 0.86% to 3.21%, respectively. The cycle intervals of the qRT-PCR assay between each dilution ranged from 2.9 to 3.8 cycles, and the lowest detection limit of the qRT-PCR assay was 10 copies/μl. The assay exhibited high specificity that was confirmed by melting curve analysis, and no cross reaction with the Seoul virus (SEOV) and other viruses (HBV, HCV and HIV) was observed. HTNV RNA was also detected in the 27 serum samples of clinical HFRS patients using the assay, and the HTNV RNA viral load ranged from 2.06×10(1) to 1.95×10(5) copies/μl. The SYBR Green Ⅰ-based one-step qRT-PCR assay is a sensitive, specific, reproducible, and simple method for detecting and quantifying HTNV in cell culture and clinical samples.",2013 Nov 21,"['Jiang, Wei', 'Yu, Hai-tao', 'Zhao, Ke', 'Zhang, Ye', 'Du, Hong', 'Wang, Ping-zhong', 'Bai, Xue-fan']",PLoS One,,,True
6da3f66c681b4b60ce1f6f246340517b79b67137,PMC,Chicken Interferon-Inducible Transmembrane Protein 3 Restricts Influenza Viruses and Lyssaviruses In Vitro,http://dx.doi.org/10.1128/JVI.01443-13,PMC3838109,24067955,CC BY,"Interferon-inducible transmembrane protein 3 (IFITM3) is an effector protein of the innate immune system. It confers potent, cell-intrinsic resistance to infection by diverse enveloped viruses both in vitro and in vivo, including influenza viruses, West Nile virus, and dengue virus. IFITM3 prevents cytosolic entry of these viruses by blocking complete virus envelope fusion with cell endosome membranes. Although the IFITM locus, which includes IFITM1, -2, -3, and -5, is present in mammalian species, this locus has not been unambiguously identified or functionally characterized in avian species. Here, we show that the IFITM locus exists in chickens and is syntenic with the IFITM locus in mammals. The chicken IFITM3 protein restricts cell infection by influenza A viruses and lyssaviruses to a similar level as its human orthologue. Furthermore, we show that chicken IFITM3 is functional in chicken cells and that knockdown of constitutive expression in chicken fibroblasts results in enhanced infection by influenza A virus. Chicken IFITM2 and -3 are constitutively expressed in all tissues examined, whereas IFITM1 is only expressed in the bursa of Fabricius, gastrointestinal tract, cecal tonsil, and trachea. Despite being highly divergent at the amino acid level, IFITM3 proteins of birds and mammals can restrict replication of viruses that are able to infect different host species, suggesting IFITM proteins may provide a crucial barrier for zoonotic infections.",2013 Dec,"['Smith, S. E.', 'Gibson, M. S.', 'Wash, R. S.', 'Ferrara, F.', 'Wright, E.', 'Temperton, N.', 'Kellam, P.', 'Fife, M.']",J Virol,,,True
765003fdad3ad535f5fd2d769ed5900e5013dda2,PMC,A Simplified Positive-Sense-RNA Virus Construction Approach That Enhances Analysis Throughput,http://dx.doi.org/10.1128/JVI.02261-13,PMC3838137,24049164,CC BY,"Here we present an approach that advances the throughput of a genetic analysis of a positive-sense RNA virus by simplifying virus construction. It enabled comprehensive dissection of a complex, multigene phenotype through rapid derivation of a large number of chimeric viruses and construction of a mutant library directly from a virus pool. The versatility of the approach described here expands the applicability of diverse genetic approaches to study these viruses.",2013 Dec,"['Siridechadilok, Bunpote', 'Gomutsukhavadee, Methee', 'Sawaengpol, Thunyarat', 'Sangiambut, Sutha', 'Puttikhunt, Chunya', 'Chin-inmanu, Kwanrutai', 'Suriyaphol, Prapat', 'Malasit, Prida', 'Screaton, Gavin', 'Mongkolsapaya, Juthathip']",J Virol,,,True
bf256a0f8fd3ff2faa39f340180e7e19bfa4c295,PMC,The Soluble Form of the EIAV Receptor Encoded by an Alternative Splicing Variant Inhibits EIAV Infection of Target Cells,http://dx.doi.org/10.1371/journal.pone.0079299,PMC3838338,24278125,CC BY,"Equine lentivirus receptor 1 (ELR1) has been identified as the sole receptor for equine infectious anemia virus (EIAV) and is a member of the tumor necrosis factor receptor (TNFR) superfamily. In addition to the previously described membrane-associated form of ELR1, two other major alternative splicing variant mRNAs were identified in equine monocyte-derived macrophages (eMDMs). One major spliced species (ELR1-IN) contained an insertion of 153 nt, which resulted in a premature stop codon situated 561 nt upstream of the predicted membrane spanning domain. The other major species (ELR1-DE) has a deletion of 109 nt that causes a shift of the open reading frame and generates a stop codon 312 nt downstream. Because ELR1-DE presumably encodes a peptide of a mere 23 residues, only ELR1-IN was further analyzed. The expression of a soluble form of ELR1 (sELR1) by ELR1-IN was confirmed by Western blot and immunofluorescence analyses. Similar to ELR1, the transcription level of ELR1-IN varied among individual horses and at different time points in the same individuals. The ratio of ELR1-IN mRNA species to ELR1 mRNA was approximately 1∶2.5. Pre-incubation of the recombinant sELR1 with EIAV significantly inhibited EIAV infection in equine macrophages, the primary in vivo target cell of the virus. Fetal equine dermal (FED) cells are susceptible to EIAV in vitro, and the replication of EIAV in FED cells transiently transfected with ELR1-IN was markedly reduced when compared with replication in cells transfected with the empty vector. Finally, the expression levels of both forms of the EIAV receptor were significantly regulated by infection with this virus. Taken together, our data indicate that sELR1 acts as a secreted cellular factor that inhibits EIAV infection in host cells.",2013 Nov 22,"['Lin, Yue-Zhi', 'Yang, Fei', 'Zhang, Shu-Qin', 'Sun, Liu-Ke', 'Wang, Xue-Feng', 'Du, Cheng', 'Zhou, Jian-Hua']",PLoS One,,,True
9fb5556c3b5fdb3bff762a42f16c21a7fa65d801,PMC,MMP-independent role of TIMP-1 at the blood brain barrier during viral encephalomyelitis,http://dx.doi.org/10.1042/AN20130033,PMC3840398,24156369,CC BY,"Infection of the CNS (central nervous system) with a sublethal neurotropic coronavirus (JHMV) induces a vigorous inflammatory response. CD4(+) and CD8(+) T cells are essential to control infectious virus but at the cost of tissue damage. An enigma in understanding the contribution of T cell subsets in pathogenesis resides in their distinct migration pattern across the BBB (blood brain barrier). CD4(+) T cells transiently accumulate within the perivascular space, whereas CD8(+) T cells migrate directly into the CNS parenchyma. As MMPs (matrix metalloproteinases) facilitate migration across the glia limitans, specific expression of the TIMP (tissue inhibitor of MMPs)-1 by CD4(+) T cells present in the perivascular cuffs suggested that TIMP-1 is responsible for stalling CD4(+) T cell migration into the CNS parenchyma. Using TIMP-1 deficient mice, the present data demonstrate an increase rather than a decrease in CD4(+) T cell accumulation within the perivascular space during JHMV infection. Whereas virus control was not affected by perivascular retention of CD4(+) T cells, disease severity was decreased and associated with reduced IFNγ (interferon γ) production. Moreover, decreased CD4(+) T cell recruitment into the CNS parenchyma of TIMP-1 deficient mice was not associated with impaired T cell recruiting chemokines or MMP expression, and no compensation by other TIMP molecules was identified. These data suggest an MMP-independent role of TIMP-1 in regulating CD4(+) T cell access into the CNS parenchyma during acute JHMV encephalitis.",2013 Nov 26,"['Savarin, Carine', 'Bergmann, Cornelia\xa0C.', 'Hinton, David\xa0R.', 'Stohlman, Stephen\xa0A.']",ASN Neuro,,,True
377bace754b08919a4139b9f1070f8ab422f90bc,PMC,Pandemic influenza viruses: time to recognize our inability to predict the unpredictable and stop dangerous gain-of-function experiments,http://dx.doi.org/10.1002/emmm.201303475,PMC3840482,24186378,CC BY,,2013 Nov 24,"Wain-Hobson, Simon",EMBO Mol Med,,,True
92911175d25c9f4bce7ace3050a4ddea1f5105eb,PMC,Efficacy of a Carrageenan nasal spray in patients with common cold: a randomized controlled trial,http://dx.doi.org/10.1186/1465-9921-14-124,PMC3840586,24219370,CC BY,"BACKGROUND: The common cold is the most widespread viral infection in humans. Iota-carrageenan has previously shown antiviral effectiveness against cold viruses in clinical trials. This study investigated the efficacy of a carrageenan-containing nasal spray on the duration of the common cold and nasal fluid viral load in adult patients. METHODS: In a randomized, double-blind, placebo-controlled trial, 211 patients suffering from early symptoms of the common cold were treated for seven days. Application was performed three times daily with either a carrageenan-supplemented nasal spray or saline solution as placebo with an overall observation period of 21 days. The primary endpoint was the duration of disease defined as the time until the last day with symptoms followed by all other days in the study period without symptoms. During the study, but prior unblinding, the definition of disease duration was adapted from the original protocol that defines disease duration as the time period of symptoms followed by 48 hours without symptoms. RESULTS: In patients showing a laboratory-confirmed cold virus infection and adherence to the protocol, alleviation of symptoms was 2.1 days faster in the carrageenan group in comparison to placebo (p = 0.037). The primary endpoint that had been prespecified but was changed before unblinding was not met. Viral titers in nasal fluids showed a significantly greater decrease in carrageenan patients in the intention-to-treat population (p = 0.024) and in the per protocol population (p = 0.018) between days 1 and 3/4. CONCLUSIONS: In adults with common cold virus infections, direct local administration of carrageenan with nasal sprays reduced the duration of cold symptoms. A significant reduction of viral load in the nasal wash fluids of patients confirmed similar findings from earlier trials in children and adults. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80148028",2013 Nov 13,"['Ludwig, Martin', 'Enzenhofer, Elisabeth', 'Schneider, Sven', 'Rauch, Margit', 'Bodenteich, Angelika', 'Neumann, Kurt', 'Prieschl-Grassauer, Eva', 'Grassauer, Andreas', 'Lion, Thomas', 'Mueller, Christian A']",Respir Res,,,True
0b227d1996bc5dfd895b43f6c6e2449c58252c67,PMC,Insufficient preparedness of primary care practices for pandemic influenza and the effect of a preparedness plan in Japan: a prefecture-wide cross-sectional study,http://dx.doi.org/10.1186/1471-2296-14-174,PMC3840630,24252688,CC BY,"BACKGROUND: Cases of emerging infectious diseases, including H5N1 influenza, H7N9 influenza, and Middle East Respiratory Syndrome, have been reported in recent years, and the threat of pandemic outbreaks persists. In Japan, primary care is the frontline against emerging infectious diseases in communities. Although the importance of pandemic preparedness in primary care has been highlighted previously, few studies have thus far investigated the preparedness among primary care practices (PCPs) or differences in the preparedness of different institutional settings. We examined PCP preparedness and response to the 2009 influenza pandemic in Japan, and explored the role of a pandemic preparedness plan during the pandemic. METHODS: We used a survey questionnaire to assess how well individual PCPs in Okinawa, Japan, were prepared for the 2009 influenza pandemic. The questionnaire was mailed to all eligible PCPs (N = 465) in Okinawa, regardless of their institutional setting. In addition, we assessed the differences in the preparedness of clinics and hospitals and determined whether the national preparedness plan affected individual preparedness and response. Data were analyzed using descriptive and logistic regression analyses. RESULTS: A total of 174 (37.4%) PCPs responded to our survey. In general, high-level personal protective equipment (PPE) such as N95 masks (45.4%), gowns (30.5%), and eye protection (21.3%) was stocked at a low rate. Clinic-based PCPs were significantly less prepared than hospital-based PCPs to provide N95 masks (OR 0.34), gowns (OR 0.15), and eye protection (OR 0.18). In addition, only 32.8% of PCPs adopted an adequate business continuity plan (BCP). After controlling for institutional setting, reading the national preparedness plan was significantly associated with establishment of a BCP (OR 5.86), and with knowledge of how to transfer a swab specimen to a local medical laboratory (OR 5.60). CONCLUSIONS: With regard to PPE availability, PCPs (especially clinic-based PCPs) were not adequately prepared for the influenza pandemic. Awareness of the national pandemic preparedness plan is likely to promote prefecture-wide implementation of BCPs and surveillance activity.",2013 Nov 19,"['Tomizuka, Taro', 'Kanatani, Yasuhiro', 'Kawahara, Kazuo']",BMC Fam Pract,,,True
2d51e2d2cbb76670bc27af8af326084f00f235db,PMC,Insufficient preparedness of primary care practices for pandemic influenza and the effect of a preparedness plan in Japan: a prefecture-wide cross-sectional study,http://dx.doi.org/10.1186/1471-2296-14-174,PMC3840630,24252688,CC BY,"BACKGROUND: Cases of emerging infectious diseases, including H5N1 influenza, H7N9 influenza, and Middle East Respiratory Syndrome, have been reported in recent years, and the threat of pandemic outbreaks persists. In Japan, primary care is the frontline against emerging infectious diseases in communities. Although the importance of pandemic preparedness in primary care has been highlighted previously, few studies have thus far investigated the preparedness among primary care practices (PCPs) or differences in the preparedness of different institutional settings. We examined PCP preparedness and response to the 2009 influenza pandemic in Japan, and explored the role of a pandemic preparedness plan during the pandemic. METHODS: We used a survey questionnaire to assess how well individual PCPs in Okinawa, Japan, were prepared for the 2009 influenza pandemic. The questionnaire was mailed to all eligible PCPs (N = 465) in Okinawa, regardless of their institutional setting. In addition, we assessed the differences in the preparedness of clinics and hospitals and determined whether the national preparedness plan affected individual preparedness and response. Data were analyzed using descriptive and logistic regression analyses. RESULTS: A total of 174 (37.4%) PCPs responded to our survey. In general, high-level personal protective equipment (PPE) such as N95 masks (45.4%), gowns (30.5%), and eye protection (21.3%) was stocked at a low rate. Clinic-based PCPs were significantly less prepared than hospital-based PCPs to provide N95 masks (OR 0.34), gowns (OR 0.15), and eye protection (OR 0.18). In addition, only 32.8% of PCPs adopted an adequate business continuity plan (BCP). After controlling for institutional setting, reading the national preparedness plan was significantly associated with establishment of a BCP (OR 5.86), and with knowledge of how to transfer a swab specimen to a local medical laboratory (OR 5.60). CONCLUSIONS: With regard to PPE availability, PCPs (especially clinic-based PCPs) were not adequately prepared for the influenza pandemic. Awareness of the national pandemic preparedness plan is likely to promote prefecture-wide implementation of BCPs and surveillance activity.",2013 Nov 19,"['Tomizuka, Taro', 'Kanatani, Yasuhiro', 'Kawahara, Kazuo']",BMC Fam Pract,,,False
ef38ed2f4cc96e16ce011623cc5d15d2d8ca58c3,PMC,Efficient generation of recombinant RNA viruses using targeted recombination-mediated mutagenesis of bacterial artificial chromosomes containing full-length cDNA,http://dx.doi.org/10.1186/1471-2164-14-819,PMC3840674,24262008,CC BY,"BACKGROUND: Infectious cDNA clones are a prerequisite for directed genetic manipulation of RNA viruses. Here, a strategy to facilitate manipulation and rescue of classical swine fever viruses (CSFVs) from full-length cDNAs present within bacterial artificial chromosomes (BACs) is described. This strategy allows manipulation of viral cDNA by targeted recombination-mediated mutagenesis within bacteria. RESULTS: A new CSFV-BAC (pBeloR26) derived from the Riems vaccine strain has been constructed and subsequently modified in the E2 coding sequence, using the targeted recombination strategy to enable rescue of chimeric pestiviruses (vR26_E2gif and vR26_TAV) with potential as new marker vaccine candidates. Sequencing of the BACs revealed a high genetic stability during passages within bacteria. The complete genome sequences of rescued viruses, after extensive passages in mammalian cells showed that modifications in the E2 protein coding sequence were stably maintained. A single amino acid substitution (D3431G) in the RNA dependent RNA polymerase was observed in the rescued viruses vR26_E2gif and vR26, which was reversion to the parental Riems sequence. CONCLUSIONS: These results show that targeted recombination-mediated mutagenesis provides a powerful tool for expediting the construction of novel RNA genomes and should be applicable to the manipulation of other RNA viruses.",2013 Nov 22,"['Rasmussen, Thomas Bruun', 'Risager, Peter Christian', 'Fahnøe, Ulrik', 'Friis, Martin Barfred', 'Belsham, Graham J', 'Höper, Dirk', 'Reimann, Ilona', 'Beer, Martin']",BMC Genomics,,,True
b3e679d6e37ba367e165971515663ecd71ea522c,PMC,Synonymous Codon Usage in TTSuV2: Analysis and Comparison with TTSuV1,http://dx.doi.org/10.1371/journal.pone.0081469,PMC3841265,24303050,CC BY,"Two species of the DNA virus Torque teno sus virus (TTSuV), TTSuV1 and TTSuV2, have become widely distributed in pig-farming countries in recent years. In this study, we performed a comprehensive analysis of synonymous codon usage bias in 41 available TTSuV2 coding sequences (CDS), and compared the codon usage patterns of TTSuV2 and TTSuV1. TTSuV codon usage patterns were found to be phylogenetically conserved. Values for the effective number of codons (ENC) indicated that the overall extent of codon usage bias in both TTSuV2 and TTSuV1 was not significant, the most frequently occurring codons had an A or C at the third codon position. Correspondence analysis (COA) was performed and TTSuV2 and TTSuV1 sequences were located in different quadrants of the first two major axes. A plot of the ENC revealed that compositional constraint was the major factor determining the codon usage bias for TTSuV2. In addition, hierarchical cluster analysis of 41 TTSuV2 isolates based on relative synonymous codon usage (RSCU) values suggested that there was no association between geographic distribution and codon bias of TTSuV2 sequences. Finally, the comparison of RSCU for TTSuV2, TTSuV1 and the corresponding host sequence indicated that the codon usage pattern of TTSuV2 was similar to that of TTSuV1. However the similarity was low for each virus and its host. These conclusions provide important insight into the synonymous codon usage pattern of TTSuV2, as well as better understangding of the molecular evolution of TTSuV2 genomes.",2013 Nov 26,"['Zhang, Zhicheng', 'Dai, Wei', 'Dai, Dingzhen']",PLoS One,,,True
39aba27d479a1340c398f332053951fb33606dcd,PMC,Positive Evolutionary Selection On the RIG-I-Like Receptor Genes in Mammals,http://dx.doi.org/10.1371/journal.pone.0081864,PMC3842351,24312370,CC BY,"The mammalian RIG-I-like receptors, RIG-I, MDA5 and LGP2, are a family of DExD/H box RNA helicases responsible for the cytoplasmic detection of viral RNA. These receptors detect a variety of RNA viruses, or DNA viruses that express unusual RNA species, many of which are responsible for a great number of severe and lethal diseases. Host innate sentinel proteins involved in pathogen recognition must rapidly evolve in a dynamic arms race with pathogens, and thus are subjected to long-term positive selection pressures to avoid potential infections. Using six codon-based Maximum Likelihood methods, we were able to identify specific codons under positive selection in each of these three genes. The highest number of positively selected codons was detected in MDA5, but a great percentage of these codons were located outside of the currently defined protein domains for MDA5, which likely reflects the imposition of both functional and structural constraints. Additionally, our results support LGP2 as being the least prone to evolutionary change, since the lowest number of codons under selection was observed for this gene. On the other hand, the preponderance of positively selected codons for RIG-I were detected in known protein functional domains, suggesting that pressure has been imposed by the vast number of viruses that are recognized by this RNA helicase. Furthermore, the RIG-I repressor domain, the region responsible for recognizing and binding to its RNA substrates, exhibited the strongest evidence of selective pressures. Branch-site analyses were performed and several species branches on the three receptor gene trees showed evidence of episodic positive selection. In conclusion, by looking for evidence of positive evolutionary selection on mammalian RIG-I-like receptor genes, we propose that a multitude of viruses have crafted the receptors biological function in host defense, specifically for the RIG-I gene, contributing to the innate species-specific resistance/susceptibility to diverse viral pathogens.",2013 Nov 27,"['Lemos de Matos, Ana', 'McFadden, Grant', 'Esteves, Pedro J.']",PLoS One,,,True
8d75437a3933156f016f8b3ef139d206c63f9bec,PMC,Positive Evolutionary Selection On the RIG-I-Like Receptor Genes in Mammals,http://dx.doi.org/10.1371/journal.pone.0081864,PMC3842351,24312370,CC BY,"The mammalian RIG-I-like receptors, RIG-I, MDA5 and LGP2, are a family of DExD/H box RNA helicases responsible for the cytoplasmic detection of viral RNA. These receptors detect a variety of RNA viruses, or DNA viruses that express unusual RNA species, many of which are responsible for a great number of severe and lethal diseases. Host innate sentinel proteins involved in pathogen recognition must rapidly evolve in a dynamic arms race with pathogens, and thus are subjected to long-term positive selection pressures to avoid potential infections. Using six codon-based Maximum Likelihood methods, we were able to identify specific codons under positive selection in each of these three genes. The highest number of positively selected codons was detected in MDA5, but a great percentage of these codons were located outside of the currently defined protein domains for MDA5, which likely reflects the imposition of both functional and structural constraints. Additionally, our results support LGP2 as being the least prone to evolutionary change, since the lowest number of codons under selection was observed for this gene. On the other hand, the preponderance of positively selected codons for RIG-I were detected in known protein functional domains, suggesting that pressure has been imposed by the vast number of viruses that are recognized by this RNA helicase. Furthermore, the RIG-I repressor domain, the region responsible for recognizing and binding to its RNA substrates, exhibited the strongest evidence of selective pressures. Branch-site analyses were performed and several species branches on the three receptor gene trees showed evidence of episodic positive selection. In conclusion, by looking for evidence of positive evolutionary selection on mammalian RIG-I-like receptor genes, we propose that a multitude of viruses have crafted the receptors biological function in host defense, specifically for the RIG-I gene, contributing to the innate species-specific resistance/susceptibility to diverse viral pathogens.",2013 Nov 27,"['Lemos de Matos, Ana', 'McFadden, Grant', 'Esteves, Pedro J.']",PLoS One,,,False
c4a6222c0b432f6757267c5c6db630859f0bcadb,PMC,Positive Evolutionary Selection On the RIG-I-Like Receptor Genes in Mammals,http://dx.doi.org/10.1371/journal.pone.0081864,PMC3842351,24312370,CC BY,"The mammalian RIG-I-like receptors, RIG-I, MDA5 and LGP2, are a family of DExD/H box RNA helicases responsible for the cytoplasmic detection of viral RNA. These receptors detect a variety of RNA viruses, or DNA viruses that express unusual RNA species, many of which are responsible for a great number of severe and lethal diseases. Host innate sentinel proteins involved in pathogen recognition must rapidly evolve in a dynamic arms race with pathogens, and thus are subjected to long-term positive selection pressures to avoid potential infections. Using six codon-based Maximum Likelihood methods, we were able to identify specific codons under positive selection in each of these three genes. The highest number of positively selected codons was detected in MDA5, but a great percentage of these codons were located outside of the currently defined protein domains for MDA5, which likely reflects the imposition of both functional and structural constraints. Additionally, our results support LGP2 as being the least prone to evolutionary change, since the lowest number of codons under selection was observed for this gene. On the other hand, the preponderance of positively selected codons for RIG-I were detected in known protein functional domains, suggesting that pressure has been imposed by the vast number of viruses that are recognized by this RNA helicase. Furthermore, the RIG-I repressor domain, the region responsible for recognizing and binding to its RNA substrates, exhibited the strongest evidence of selective pressures. Branch-site analyses were performed and several species branches on the three receptor gene trees showed evidence of episodic positive selection. In conclusion, by looking for evidence of positive evolutionary selection on mammalian RIG-I-like receptor genes, we propose that a multitude of viruses have crafted the receptors biological function in host defense, specifically for the RIG-I gene, contributing to the innate species-specific resistance/susceptibility to diverse viral pathogens.",2013 Nov 27,"['Lemos de Matos, Ana', 'McFadden, Grant', 'Esteves, Pedro J.']",PLoS One,,,False
1c5dd9051932934f62921f37a1d2a3d739fd4a95,PMC,Positive Evolutionary Selection On the RIG-I-Like Receptor Genes in Mammals,http://dx.doi.org/10.1371/journal.pone.0081864,PMC3842351,24312370,CC BY,"The mammalian RIG-I-like receptors, RIG-I, MDA5 and LGP2, are a family of DExD/H box RNA helicases responsible for the cytoplasmic detection of viral RNA. These receptors detect a variety of RNA viruses, or DNA viruses that express unusual RNA species, many of which are responsible for a great number of severe and lethal diseases. Host innate sentinel proteins involved in pathogen recognition must rapidly evolve in a dynamic arms race with pathogens, and thus are subjected to long-term positive selection pressures to avoid potential infections. Using six codon-based Maximum Likelihood methods, we were able to identify specific codons under positive selection in each of these three genes. The highest number of positively selected codons was detected in MDA5, but a great percentage of these codons were located outside of the currently defined protein domains for MDA5, which likely reflects the imposition of both functional and structural constraints. Additionally, our results support LGP2 as being the least prone to evolutionary change, since the lowest number of codons under selection was observed for this gene. On the other hand, the preponderance of positively selected codons for RIG-I were detected in known protein functional domains, suggesting that pressure has been imposed by the vast number of viruses that are recognized by this RNA helicase. Furthermore, the RIG-I repressor domain, the region responsible for recognizing and binding to its RNA substrates, exhibited the strongest evidence of selective pressures. Branch-site analyses were performed and several species branches on the three receptor gene trees showed evidence of episodic positive selection. In conclusion, by looking for evidence of positive evolutionary selection on mammalian RIG-I-like receptor genes, we propose that a multitude of viruses have crafted the receptors biological function in host defense, specifically for the RIG-I gene, contributing to the innate species-specific resistance/susceptibility to diverse viral pathogens.",2013 Nov 27,"['Lemos de Matos, Ana', 'McFadden, Grant', 'Esteves, Pedro J.']",PLoS One,,,False
c7d8100f9f9f799f495a0458c8f23dcc7bcec3ec,PMC,Efficacy of cineole in patients suffering from acute bronchitis: a placebo-controlled double-blind trial,http://dx.doi.org/10.1186/1745-9974-9-25,PMC3842692,24261680,CC BY,"OBJECTIVE: Cineole has mucolytic, bronchodilating and anti-inflammatory properties and reduces the exacerbation rate in patients suffering from COPD, as well as ameliorates symptoms in patients suffering from asthma and rhinosinusitis. Based on these effects, we therefore postulated the hypothesis that patients with acute bronchitis would also benefit from therapy with Cineole. METHODS: As part of a double-blind, placebo-controlled, multi-center-study, a total of 242 patients with confirmed acute bronchitis was randomly selected to participate. Over a period of 10 days, all patients were administered 3 x 200 mg of Cineole, or a respective placebo, per day. The primary outcome measure was a Bronchitis Sum Score, which summarises the relevant symptoms of acute bronchitis. RESULTS: After 4 days of treatment it was notable, that the patient group treated with Cineole, showed significantly more improvements of the bronchitis-sum-score than those of the placebo group (p = 0.0383). The statistical significant difference of the individual outcome measures was especially underlined by the frequency of cough fits by p = 0.0001 after 4 days. CONCLUSIONS: The effects of Cineole in the treatment of acute bronchitis were clearly measurable and could be proven after a treatment period of merely 4 days. This study corroborates the fact that Cineole actively and significantly reduces cough frequency after four days. Therefore it has been shown to have a great socioeconomic impact. TRIAL REGISTRATION: ISRCTN: ISRCTN37784439",2013 Nov 21,"['Fischer, Juergen', 'Dethlefsen, Uwe']",Cough,,,True
378082edc2f3e85e6cc8941c81030a70c65c7f8f,PMC,Dendritic Cell-Specific Delivery of Flt3L by Coronavirus Vectors Secures Induction of Therapeutic Antitumor Immunity,http://dx.doi.org/10.1371/journal.pone.0081442,PMC3842931,24312302,CC BY,"Efficacy of antitumor vaccination depends to a large extent on antigen targeting to dendritic cells (DCs). Here, we assessed antitumor immunity induced by attenuated coronavirus vectors which exclusively target DCs in vivo and express either lymphocyte- or DC-activating cytokines in combination with a GFP-tagged model antigen. Tracking of in vivo transduced DCs revealed that vectors encoding for Fms-like tyrosine kinase 3 ligand (Flt3L) exhibited a higher capacity to induce DC maturation compared to vectors delivering IL-2 or IL-15. Moreover, Flt3L vectors more efficiently induced tumor-specific CD8(+) T cells, expanded the epitope repertoire, and provided both prophylactic and therapeutic tumor immunity. In contrast, IL-2- or IL-15-encoding vectors showed a substantially lower efficacy in CD8(+) T cell priming and failed to protect the host once tumors had been established. Thus, specific in vivo targeting of DCs with coronavirus vectors in conjunction with appropriate conditioning of the microenvironment through Flt3L represents an efficient strategy for the generation of therapeutic antitumor immunity.",2013 Nov 28,"['Perez-Shibayama, Christian', 'Gil-Cruz, Cristina', 'Nussbacher, Monika', 'Allgäuer, Eva', 'Cervantes-Barragan, Luisa', 'Züst, Roland', 'Ludewig, Burkhard']",PLoS One,,,True
5ff6f535016d7b46687474786efd07db9c19ce8e,PMC,Investigation of serum protein profiles in scrapie infected sheep by means of SELDI-TOF-MS and multivariate data analysis,http://dx.doi.org/10.1186/1756-0500-6-466,PMC3843553,24229425,CC BY,"BACKGROUND: Classical scrapie in sheep is a fatal neurodegenerative disease associated with the conversion PrP(C) to PrP(Sc). Much is known about genetic susceptibility, uptake and dissemination of PrP(Sc) in the body, but many aspects of prion diseases are still unknown. Different proteomic techniques have been used during the last decade to investigate differences in protein profiles between affected animals and healthy controls. We have investigated the protein profiles in serum of sheep with scrapie and healthy controls by SELDI-TOF-MS and LC-MS/MS. Latent Variable methods such as Principal Component Analysis, Partial Least Squares-Discriminant Analysis and Target Projection methods were used to describe the MS data. RESULTS: The serum proteomic profiles showed variable differences between the groups both throughout the incubation period and at the clinical end stage of scrapie. At the end stage, the target projection model separated the two groups with a sensitivity of 97.8%, and serum amyloid A was identified as one of the protein peaks that differed significantly between the groups. CONCLUSIONS: At the clinical end stage of classical scrapie, ten SELDI peaks significantly discriminated the scrapie group from the healthy controls. During the non-clinical incubation period, individual SELDI peaks were differently expressed between the groups at different time points. Investigations of differences in -omic profiles can contribute to new insights into the underlying disease processes and pathways, and advance our understanding of prion diseases, but comparison and validation across laboratories is difficult and challenging.",2013 Nov 14,"['Meling, Siv', 'Kvalheim, Olav M', 'Arneberg, Reidar', 'Bårdsen, Kjetil', 'Hjelle, Anne', 'Ulvund, Martha J']",BMC Res Notes,,,True
9976bf51302bf33a5384a30c73231d4077c63ffe,PMC,"Genotyping and pathobiologic characterization of canine parvovirus circulating in Nanjing, China",http://dx.doi.org/10.1186/1743-422X-10-272,PMC3844316,23988202,CC BY,"BACKGROUND: Canine parvovirus (CPV) is an important pathogen that causes acute enteric disease in dogs. It has mutated and spread throughout the world in dog populations. We provide an update on the molecular characterization of CPV that circulated in Nanjing, a provincial capital in China between 2009 and 2012. RESULTS: Seventy rectal swab samples were collected from the dogs diagnosed with CPV infection in 8 animal hospitals of Nanjing. Sequence analysis of VP2 genes of 31 samples revealed that 29 viral strains belonged to CPV-2a subtype, while other two strains were classified into CPV-2b. To investigate the pathogenicity of the prevalent virus, we isolated CPV-2a and performed the animal experiment. Nine beagles were inoculated with 10(5.86) of 50% tissue culture infectious doses (TCID(50)) of the virus. All the experimentally infected beagles exhibited mild to moderate mucoid or watery diarrhea on day 4 post-infection (p.i.). On day 9 p.i., characteristic histopathological lesions were clearly observed in multiple organs of infected dogs, including liver, spleen, kidney, brain and all segments of the small and large intestines, while viral DNA and antigen staining could be detected in the sampled tissues. It is notable that canine parvovirus was isolated in one from two brain samples processed. CONCLUSION: Our results indicated that CPV-2a is the predominant subtype in Nanjing of China. And this virus caused extensive lesions in a variety of tissues, including the brain.",2013 Aug 29,"['Zhao, Yanbing', 'Lin, Yan', 'Zeng, Xujian', 'Lu, Chengping', 'Hou, Jiafa']",Virol J,,,True
fa93cc1d684bce742748b879031332537855f5ec,PMC,The Effect of Postoperative Corticosteroid Administration on Free Vascularized Fibular Grafting for Treating Osteonecrosis of the Femoral Head,http://dx.doi.org/10.1155/2013/708014,PMC3845513,24324377,CC BY,"Free vascularized fibular grafting (FVFG) has been reported to be an effective method of treating osteonecrosis of the femoral head (ONFH). This study evaluated whether postoperative maintenance doses of corticosteroids had an adverse effect on FVFG outcomes in patients with corticosteroid-induced ONFH. We retrospectively reviewed the records of 39 patients (67 hips) who had received maintenance doses of corticosteroids following FVFG. This group was matched to a group of patients who had not received corticosteroids treatment after operation. The mean follow-up duration was 5.4 years for the postoperative corticosteroid administration group (PCA group) and 5.0 years for the control group. At the latest follow-up, the average increase in Harris hip score was 11.1 ± 8.7 points for all hips in the PCA group and 12.6 ± 7.4 points for all hips in the control group (P > 0.05). In the PCA group, through radiographic evaluation, 49 hips were improved, 10 hips appeared unchanged, and 8 hips appeared worse. In the control group, 47 hips were improved, 13 hips appeared unchanged, and 7 hips appeared worse. The results suggested that postoperative maintenance doses of corticosteroids do not have an adverse effect on FVFG outcomes in patients with corticosteroid-induced ONFH.",2013 Nov 12,"['Ding, Hao', 'Chen, Sheng-Bao', 'Lin, Sen', 'Gao, You-Shui', 'Zhang, Chang-Qing']",ScientificWorldJournal,,,True
70542f1f1a2ced1e26658f62372e882da4c2b366,PMC,Effectiveness of cough etiquette maneuvers in disrupting the chain of transmission of infectious respiratory diseases,http://dx.doi.org/10.1186/1471-2458-13-811,PMC3846148,24010919,CC BY,"BACKGROUND: The effectiveness of recommended measures, such as “cover your mouth when coughing”, in disrupting the chain of transmission of infectious respiratory diseases (IRD) has been questioned. The objective of the current study was to determine the effectiveness of simple primary respiratory hygiene/cough etiquette maneuvers in blocking droplets expelled as aerosol during coughing. METHOD: In this study, 31 healthy non-smokers performed cough etiquette maneuvers in an effort to cover their voluntarily elicited best effort coughs in an open bench format. A laser diffraction system was used to obtain accurate, non-invasive, quantitative, real time measurements of the size and number of droplets emitted during the assessed cough etiquette maneuvers. RESULTS: Recommended cough etiquette maneuvers did not block the release and dispersion of a variety of different diameter droplets to the surrounding environment. Droplets smaller than one-micron size dominate the total number of droplets leaked when practicing assessed maneuvers. CONCLUSIONS: All the assessed cough etiquette maneuvers, performed as recommended, do not block droplets expelled as aerosol when coughing. This aerosol can penetrate profound levels of the respiratory system. Practicing these assessed primary respiratory hygiene/cough etiquette maneuvers would still permit direct, indirect, and/or airborne transmission and spread of IRD, such as influenza and Tuberculosis. All the assessed cough etiquette maneuvers, as recommended, do not fully interrupt the chain of transmission of IRD. This knowledge urges us all to critically review recommended CE and to search for new evidence-based procedures that effectively disrupt the transmission of respiratory pathogens. Interrupting the chain of transmission of IRD will optimize the protection of first responders, paramedics, nurses, and doctors working in triage sites, emergency rooms, intensive care units, and the general public against cough-droplet-spread diseases.",2013 Sep 8,"['Zayas, Gustavo', 'Chiang, Ming C', 'Wong, Eric', 'MacDonald, Fred', 'Lange, Carlos F', 'Senthilselvan, Ambikaipakan', 'King, Malcolm']",BMC Public Health,,,True
6f0572cc1fa39ecc775cf576db694638a7fb9bc1,PMC,Bacterial artificial chromosome derived simian varicella virus is pathogenic in vivo,http://dx.doi.org/10.1186/1743-422X-10-278,PMC3846606,24010815,CC BY,"BACKGROUND: Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus that infects humans and results in chickenpox and herpes zoster. A number of VZV genes remain functionally uncharacterized and since VZV is an obligate human pathogen, rigorous evaluation of VZV mutants in vivo remains challenging. Simian varicella virus (SVV) is homologous to VZV and SVV infection of rhesus macaques (RM) closely mimics VZV infection of humans. Recently the SVV genome was cloned as a bacterial artificial chromosome (BAC) and BAC-derived SVV displayed similar replication kinetics as wild-type (WT) SVV in vitro. METHODS: RMs were infected with BAC-derived SVV or WT SVV at 4x10(5) PFU intrabronchially (N=8, 4 per group, sex and age matched). We collected whole blood (PBMC) and bronchoalveolar lavage (BAL) at various days post-infection (dpi) and sensory ganglia during latent infection (>84 dpi) at necropsy and compared disease progression, viral replication, immune response and the establishment of latency. RESULTS: Viral replication kinetics and magnitude in bronchoalveolar lavage cells and whole blood as well as rash severity and duration were similar in RMs infected with SVV BAC or WT SVV. Moreover, SVV-specific B and T cell responses were comparable between BAC and WT-infected animals. Lastly, we measured viral DNA in sensory ganglia from both cohorts of infected RMs during latent infection. CONCLUSIONS: SVV BAC is as pathogenic and immunogenic as WT SVV in vivo. Thus, the SVV BAC genetic system combined with the rhesus macaque animal model can further our understanding of viral ORFs important for VZV pathogenesis and the development of second-generation vaccines.",2013 Sep 8,"['Meyer, Christine', 'Dewane, Jesse', 'Haberthur, Kristen', 'Engelmann, Flora', 'Arnold, Nicole', 'Gray, Wayne', 'Messaoudi, Ilhem']",Virol J,,,True
38eee3781e1192464696b9a1164834259214cde9,PMC,Calf-Level Factors Associated with Bovine Neonatal Pancytopenia – A Multi-Country Case-Control Study,http://dx.doi.org/10.1371/journal.pone.0080619,PMC3846664,24312485,CC BY,"Bovine neonatal pancytopenia (BNP), a high fatality condition causing haemorrhages in calves aged less than 4 weeks, was first reported in 2007 in Germany and subsequently observed at low incidence in other European countries and New Zealand. A multi-country matched case-control study was conducted in 2011 to identify calf-level risk factors for BNP. 405 BNP cases were recruited from 330 farms in Belgium, France, Germany and the Netherlands by laboratory confirmation of farmer-reported cases. Up to four calves of similar age from the same farm were selected as controls (1154 calves). Risk factor data were collected by questionnaire. Multivariable modelling using conditional logistic regression indicated that PregSure®BVD (PregSure, Pfizer Animal Health) vaccination of the dam was strongly associated with BNP cases (adjusted matched Odds Ratio - amOR 17.8 first lactation dams; 95% confidence interval – ci 2.4, 134.4; p = 0.005), and second or more lactation PregSure-vaccinated dams were more likely to have a case than first lactation vaccinated dams (amOR 2.2 second lactation; ci 1.1, 4.3; p = 0.024; amOR 5.3 third or more lactation; ci 2.9, 9.8; p = <0.001). Feeding colostrum from other cows was strongly associated with BNP if the dam was not PregSure-vaccinated (amOR 30.5; ci 2.1, 440.5; p = 0.012), but the effect was less if the dam was PregSure-vaccinated (amOR 2.1; ci 1.1, 4.0; p = 0.024). Feeding exclusively dam’s milk was a higher risk than other types of milk (amOR 3.4; ci 1.6, 7.5; p = 0.002). The population attributable fractions were 0.84 (ci 0.68, 0.92) for PregSure vaccination, 0.13 (ci 0.06, 0.19) for feeding other cows’ colostrum, and 0.15 (ci 0.08, 0.22) for feeding dam’s milk. No other calf-level factors were identified, suggesting that there are other important factors that are outside the scope of this study, such as genetics, which explain why BNP develops in some PregSure-colostrum-exposed calves but not in others.",2013 Dec 2,"['Jones, Bryony A.', 'Sauter-Louis, Carola', 'Henning, Joerg', 'Stoll, Alexander', 'Nielen, Mirjam', 'Van Schaik, Gerdien', 'Smolenaars, Anja', 'Schouten, Matthijs', 'den Uijl, Ingrid', 'Fourichon, Christine', 'Guatteo, Raphael', 'Madouasse, Aurélien', 'Nusinovici, Simon', 'Deprez, Piet', 'De Vliegher, Sarne', 'Laureyns, Jozef', 'Booth, Richard', 'Cardwell, Jackie M.', 'Pfeiffer, Dirk U.']",PLoS One,,,True
5c3f5dde0537e3072d046990501a4e71471d9ddc,PMC,DC-SIGN gene promoter variants and IVIG treatment response in Kawasaki disease,http://dx.doi.org/10.1186/1546-0096-11-32,PMC3847673,24006904,CC BY,"BACKGROUND: Genetic variants in the inhibiting FcγRIIB mediate anti-inflammatory responses and influence IVIG refractoriness (IVIG-R). However, these variants are rare in Asian and Hispanic populations so other genes in the pathway could be potentially involved. IVIG is ineffective in mice lacking SIGN-R1, a related molecule to human DC-SIGN. Further, DC-SIGN is a known receptor for sialylated Fc, the component responsible for the anti-inflammatory action of IVIG. Thus, we hypothesized that DC-SIGN would also be involved in the pathway of IVIG response in Kawasaki Disease (KD) patients. FINDINGS: A case-control approach was performed to examine the differential distribution of five single nucleotide polymorphisms (SNPs) in DC-SIGN promoter with IVIG-R among White (158 vs. 62), Asian (64 vs. 12) and Hispanic (55 vs. 20) KD patients. Distinct differences in allele frequency distributions of several variants in the DC-SIGN promoter were observed in the three ethnic groups. Further, Asians with the major allele “A” in rs2287886 were more likely (OR = 1.76, p = 0.04) to be IVIG non-responder, but this allele is a minor allele in other two ethnic groups, where the association was not apparent. CONCLUSIONS: DC-SIGN can potentially complement the role of FcγRIIB in the anti-inflammatory cascade involved in the IVIG response mechanism.",2013 Sep 5,"['Portman, Michael A', 'Wiener, Howard W', 'Silva, Miriam', 'Shendre, Aditi', 'Shrestha, Sadeep']",Pediatr Rheumatol Online J,,,True
2a79ac3a49714d75cfc75c28df0a4e33d9362969,PMC,Respiratory virus surveillance in hospitalised pneumonia patients on the Thailand-Myanmar border,http://dx.doi.org/10.1186/1471-2334-13-434,PMC3847692,24498873,CC BY,"BACKGROUND: Pneumonia is a significant cause of morbidity and mortality in the developing world. Viruses contribute significantly to pneumonia burden, although data for low-income and tropical countries are scarce. The aim of this laboratory-enhanced, hospital-based surveillance was to characterise the epidemiology of respiratory virus infections among refugees living on the Thailand-Myanmar border. METHODS: Maela camp provides shelter for ~45,000 refugees. Inside the camp, a humanitarian organisation provides free hospital care in a 158-bed inpatient department (IPD). Between 1st April 2009 and 30th September 2011, all patients admitted to the IPD with a clinical diagnosis of pneumonia were invited to participate. Clinical symptoms and signs were recorded and a nasopharyngeal aspirate (NPA) collected. NPAs were tested for adenoviruses, human metapneumovirus (hMPV), influenza A & B, and RSV by PCR. RESULTS: Seven hundred eight patient episodes (698 patients) diagnosed as pneumonia during the enhanced surveillance period were included in this analysis. The median patient age was 1 year (range: < 1-70), and 90.4% were aged < 5 years. At least one virus was detected in 53.7% (380/708) of episodes. Virus detection was more common in children aged < 5 years old (<1 year: OR 2.0, 95% CI 1.2-3.4, p = 0.01; 1-4 years: OR 1.4, 95% CI 0.8-2.3, p = 0.2). RSV was detected in 176/708 (24.9%); an adenovirus in 133/708 (18.8%); an influenza virus in 68/708 (9.6%); and hMPV in 33/708 (4.7%). Twenty-eight episodes of multiple viral infections were identified, most commonly adenovirus plus another virus. RSV was more likely to be detected in children <5 years (OR 12.3, 95% CI 3.0-50.8, p = 0.001) and influenza viruses in patients ≥5 years (OR 2.8, 95% CI 1.5-5.4, p = 0.002). IPD treatment was documented in 702/708 cases; all but one patient received antimicrobials, most commonly a beta-lactam (amoxicillin/ampicillin +/−gentamicin in 664/701, 94.7%). CONCLUSIONS: Viral nucleic acid was identified in the nasopharynx in half the patients admitted with clinically diagnosed pneumonia. Development of immunisations targeting common respiratory viruses is likely to reduce the incidence of pneumonia in children living refugee camps and similar settings.",2013 Sep 16,"['Turner, Paul', 'Turner, Claudia', 'Watthanaworawit, Wanitda', 'Carrara, Verena', 'Cicelia, Naw', 'Deglise, Carole', 'Phares, Christina', 'Ortega, Luis', 'Nosten, Francois']",BMC Infect Dis,,,True
112c03868171e79e5f64b72e7c837fd4875d88f4,PMC,Comparison of viremia of type II porcine reproductive and respiratory syndrome virus in naturally infected pigs by zip nucleic acid probe-based real-time PCR,http://dx.doi.org/10.1186/1746-6148-9-181,PMC3847877,24028493,CC BY,"BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a RNA virus with high genetic variation. This virus causes significant economic losses in most pig-producing countries. The clinical presentation of PRRSV ranges from asymptomatic to devastating. In this study, we developed a sensitive and specific zip nucleic acid probe-based real-time PCR assay to evaluate the viremia of natural PRRSV-infected pigs in Taiwan. Serum samples were collected from 577 pigs aged 5–12 weeks. These include 444 clinically healthy pigs and 133 symptomatic pigs were confirmed to have porcine respiratory disease complex (PRDC). RESULTS: Viremia was quantified in 79 of the 444 (17.8%) clinically healthy pigs and in 112 of the 133 (84.2%) PRDC cases. Viremias were significantly more common in pigs with PRDC compared with the clinically healthy pigs (P <0.0001). These results suggest that a high viral load is a major feature of PRRSV-affected pigs. CONCLUSIONS: ZNA probe-based real-time PCR can be a useful tool to diagnose symptomatic and asymptomatic PRRSV-infected pigs. The presence of this marker in a sample of animals with high PRRSV loads (>10(4.2) PRRSV genomes/μl of serum) seems to indicate that it correlates with the presence of PRDC in pigs.",2013 Sep 12,"['Lin, Chao-Nan', 'Lin, Wei-Hao', 'Hung, Li-Ning', 'Wang, Sheng-Yuan', 'Chiou, Ming-Tang']",BMC Vet Res,,,True
3d7aeae7fc9f39f80a461b590c16fd9ea37aa9d7,PMC,Differential cellular gene expression in duck trachea infected with a highly or low pathogenic H5N1 avian influenza virus,http://dx.doi.org/10.1186/1743-422X-10-279,PMC3848638,24015922,CC BY,"BACKGROUND: Avian influenza A (AI) viruses of subtypes H5 can cause serious disease outbreaks in poultry including panzootic due to H5N1 highly pathogenic (HP) viruses. These viruses are a threat not only for animal health but also public health due to their zoonotic potential. The domestic duck plays a major role in the epidemiological cycle of influenza virus subtypes H5 but little is known concerning host/pathogen interactions during influenza infection in duck species. In this study, a subtracted library from duck trachea (a primary site of influenza virus infection) was constructed to analyse and compare the host response after a highly or low pathogenic (LP) H5N1-infection. RESULTS: Here, we show that more than 200 different genes were differentially expressed in infected duck trachea to a significant degree. In addition, significant differentially expressed genes between LPAI- and HPAI-infected tracheas were observed. Gene ontology annotation was used and specific signalling pathways were identified. These pathways were different for LPAI and HPAI-infected tracheas, except for the CXCR4 signalling pathway which is implicated in immune response. A different modulation of genes in the CXCR4 signalling pathway and TRIM33 was induced in duck tracheas infected with a HPAI- or a LPAI-H5N1. CONCLUSION: First, this study indicates that Suppressive Subtractive Hybridization (SSH) is an alternative approach to gain insights into the pathogenesis of influenza infection in ducks. Secondly, the results indicate that cellular gene expression in the duck trachea was differently modulated after infection with a LPAI-H5N1 or after infection with a HPAI-H5N1 virus. Such difference found in infected trachea, a primary infection site, could precede continuation of infection and could explain appearance of respiratory symptoms or not.",2013 Sep 10,"['Massin, Pascale', 'Deleage, Claire', 'Oger, Aurélie', 'Briand, François-Xavier', 'Quenault, Hélène', 'Blanchard, Yannick']",Virol J,,,True
287efc07973e7b2d046c7664771dc2e2a00b501b,PMC,First infection by all four non-severe acute respiratory syndrome human coronaviruses takes place during childhood,http://dx.doi.org/10.1186/1471-2334-13-433,PMC3848659,24040960,CC BY,"BACKGROUND: Non-severe acute respiratory syndrome (non-SARS)-related human coronaviruses (HCoVs), including HCoV-229E, -HKU1, -NL63, and -OC43, have been detected in respiratory tract samples from children and adults. However, the natural prevalence of antibodies against these viruses in serum among population is unknown. METHODS: To measure antibodies to the spike (S) protein of the four common non-SARS HCoVs, recombinant S proteins of the four HCoVs were expressed and characterised in 293 T cell. An S-protein-based indirect immunofluorescence assay (IFA) was then developed to detect anti-S IgG and IgM for the four individual HCoVs and applied to serum samples from a general asymptomatic population (218 children and 576 adults) in Beijing. RESULTS: Of 794 blood samples tested, only 29 (3.65%) were negative for anti-S IgG. The seropositivity of the four anti-S IgG antibodies was >70% within the general population. The majority of seroconversions to four-HCoV positivity first occurred in children. Both S-IgG and S-IgM antibodies were detectable among children and increased with age, reaching a plateau at 6 years of age. However, no anti-S IgM was detected in healthy adults. CONCLUSION: Large proportions of children and adults in Beijing have evidence of anti-S IgG against four the HCoVs, and first infections by all four non-SARS HCoVs takes place during childhood.",2013 Sep 16,"['Zhou, Weimin', 'Wang, Wen', 'Wang, Huijuan', 'Lu, Roujian', 'Tan, Wenjie']",BMC Infect Dis,,,True
0480084eefee6333df832a821af8945ea7ab379a,PMC,A survey of visitors on Swedish livestock farms with reference to the spread of animal diseases,http://dx.doi.org/10.1186/1746-6148-9-184,PMC3848732,24040830,CC BY,"BACKGROUND: In addition to livestock movements, other between-farm contacts such as visitors may contribute to the spread of contagious animal diseases. Knowledge about such contacts is essential for contingency planning. Preventive measures, risk-based surveillance and contact tracing may be facilitated if the frequency and type of between-farm contacts can be assessed for different types of farms. The aim of this study was to investigate the frequency and types of visitors on farms with cloven-hoofed animals in Sweden and to analyse whether there were differences in the number of visitors attributable to region, season, and type of herd. Data were collected from Swedish farmers through contact-logs covering two-week periods during four different seasons. RESULTS: In total, 482 (32%) farmers filled in the contact log for at least one period and the data represent 18,416 days. The average number of professional and non-professional visitors per day was 0.3 and 0.8, respectively. Whereas the number of professional visitors seemed to increase with increasing herd size, this relation was not seen for non-professional visits. The mean numbers of visitors per day were highest in the summer and in the farm category ‘small mixed farm’. Reports of the visitors’ degree of contact with the animals showed that veterinarians, AI-technicians, animal transporters and neighbours were often in direct contact with the animals or entered the stables and 8.8% of the repairmen were also in direct contact with animals, which was unexpected. In a multivariable analysis, species, herd size and season were significantly associated with the number of professional visitors as well as the number of visitors in direct contact with the animals. CONCLUSION: In conclusion there was a large variation between farms in the number and type of contacts. The number of visitors that may be more likely to spread diseases between farms was associated with animal species and herd size.",2013 Sep 16,"['Nöremark, Maria', 'Frössling, Jenny', 'Lewerin, Susanna Sternberg']",BMC Vet Res,,,True
712dc64a26edbb44c0e9372a9443f7292a87bf80,PMC,A survey of visitors on Swedish livestock farms with reference to the spread of animal diseases,http://dx.doi.org/10.1186/1746-6148-9-184,PMC3848732,24040830,CC BY,"BACKGROUND: In addition to livestock movements, other between-farm contacts such as visitors may contribute to the spread of contagious animal diseases. Knowledge about such contacts is essential for contingency planning. Preventive measures, risk-based surveillance and contact tracing may be facilitated if the frequency and type of between-farm contacts can be assessed for different types of farms. The aim of this study was to investigate the frequency and types of visitors on farms with cloven-hoofed animals in Sweden and to analyse whether there were differences in the number of visitors attributable to region, season, and type of herd. Data were collected from Swedish farmers through contact-logs covering two-week periods during four different seasons. RESULTS: In total, 482 (32%) farmers filled in the contact log for at least one period and the data represent 18,416 days. The average number of professional and non-professional visitors per day was 0.3 and 0.8, respectively. Whereas the number of professional visitors seemed to increase with increasing herd size, this relation was not seen for non-professional visits. The mean numbers of visitors per day were highest in the summer and in the farm category ‘small mixed farm’. Reports of the visitors’ degree of contact with the animals showed that veterinarians, AI-technicians, animal transporters and neighbours were often in direct contact with the animals or entered the stables and 8.8% of the repairmen were also in direct contact with animals, which was unexpected. In a multivariable analysis, species, herd size and season were significantly associated with the number of professional visitors as well as the number of visitors in direct contact with the animals. CONCLUSION: In conclusion there was a large variation between farms in the number and type of contacts. The number of visitors that may be more likely to spread diseases between farms was associated with animal species and herd size.",2013 Sep 16,"['Nöremark, Maria', 'Frössling, Jenny', 'Lewerin, Susanna Sternberg']",BMC Vet Res,,,False
73761176155e77d6873806dd9579f59e5419111a,PMC,An easy operating pathogen microarray (EOPM) platform for rapid screening of vertebrate pathogens,http://dx.doi.org/10.1186/1471-2334-13-437,PMC3848773,24053492,CC BY,"BACKGROUND: Infectious diseases emerge frequently in China, partly because of its large and highly mobile population. Therefore, a rapid and cost-effective pathogen screening method with broad coverage is required for prevention and control of infectious diseases. The availability of a large number of microbial genome sequences generated by conventional Sanger sequencing and next generation sequencing has enabled the development of a high-throughput high-density microarray platform for rapid large-scale screening of vertebrate pathogens. METHODS: An easy operating pathogen microarray (EOPM) was designed to detect almost all known pathogens and related species based on their genomic sequences. For effective identification of pathogens from EOPM data, a statistical enrichment algorithm has been proposed, and further implemented in a user-friendly web-based interface. RESULTS: Using multiple probes designed to specifically detect a microbial genus or species, EOPM can correctly identify known pathogens at the species or genus level in blinded testing. Despite a lower sensitivity than PCR, EOPM is sufficiently sensitive to detect the predominant pathogens causing clinical symptoms. During application in two recent clinical infectious disease outbreaks in China, EOPM successfully identified the responsible pathogens. CONCLUSIONS: EOPM is an effective surveillance platform for infectious diseases, and can play an important role in infectious disease control.",2013 Sep 20,"['Huang, Weiwei', 'Yang, Yinhui', 'Zhang, Xinlei', 'Zhao, Changan', 'Yin, Aihua', 'Zhang, Xiaozhuang', 'He, Zhengxin', 'Jiang, Yongqiang', 'Zhang, Liang']",BMC Infect Dis,,,True
5b263e22abc98f73d06f4d7baa292027c941f3c6,PMC,Dengue virus infection induces autophagy: an in vivo study,http://dx.doi.org/10.1186/1423-0127-20-65,PMC3848819,24011333,CC BY,"BACKGROUND: We and others have reported that autophagy is induced by dengue viruses (DVs) in various cell lines, and that it plays a supportive role in DV replication. This study intended to clarify whether DV infection could induce autophagy in vivo. Furthermore, the effect of DV induced autophagy on viral replication and DV-related pathogenesis was investigated. RESULTS AND CONCLUSIONS: The physiopathological parameters were evaluated after DV2 was intracranially injected into 6-day-old ICR suckling mice. Autophagy-related markers were monitored by immunohistochemical/immunofluorescent staining and Western blotting. Double-membrane autophagic vesicles were investigated by transmission-electron-microscopy. DV non-structural-protein-1 (NS1) expression (indicating DV infection) was detected in the cerebrum, medulla and midbrain of the infected mice. In these infected tissues, increased LC3 puncta formation, LC3-II expression, double-membrane autophagosome-like vesicles (autophagosome), amphisome, and decreased p62 accumulation were observed, indicating that DV2 induces the autophagic progression in vivo. Amphisome formation was demonstrated by colocalization of DV2-NS1 protein or LC3 puncta and mannose-6-phosphate receptor (MPR, endosome marker) in DV2-infected brain tissues. We further manipulated DV-induced autophagy by the inducer rapamycin and the inhibitor 3-methyladenine (3MA), which accordingly promoted or suppressed the disease symptoms and virus load in the brain of the infected mice. We demonstrated that DV2 infection of the suckling mice induces autophagy, which plays a promoting role in DV replication and pathogenesis.",2013 Sep 8,"['Lee, Ying-Ray', 'Hu, Hsuan-Yun', 'Kuo, Szu-Han', 'Lei, Huan-Yao', 'Lin, Yee-Shin', 'Yeh, Trai-Ming', 'Liu, Ching-Chuan', 'Liu, Hsiao-Sheng']",J Biomed Sci,,,True
cd2c52484c1f755ce9d2c18174aae3ae879d221f,PMC,Dengue virus infection induces autophagy: an in vivo study,http://dx.doi.org/10.1186/1423-0127-20-65,PMC3848819,24011333,CC BY,"BACKGROUND: We and others have reported that autophagy is induced by dengue viruses (DVs) in various cell lines, and that it plays a supportive role in DV replication. This study intended to clarify whether DV infection could induce autophagy in vivo. Furthermore, the effect of DV induced autophagy on viral replication and DV-related pathogenesis was investigated. RESULTS AND CONCLUSIONS: The physiopathological parameters were evaluated after DV2 was intracranially injected into 6-day-old ICR suckling mice. Autophagy-related markers were monitored by immunohistochemical/immunofluorescent staining and Western blotting. Double-membrane autophagic vesicles were investigated by transmission-electron-microscopy. DV non-structural-protein-1 (NS1) expression (indicating DV infection) was detected in the cerebrum, medulla and midbrain of the infected mice. In these infected tissues, increased LC3 puncta formation, LC3-II expression, double-membrane autophagosome-like vesicles (autophagosome), amphisome, and decreased p62 accumulation were observed, indicating that DV2 induces the autophagic progression in vivo. Amphisome formation was demonstrated by colocalization of DV2-NS1 protein or LC3 puncta and mannose-6-phosphate receptor (MPR, endosome marker) in DV2-infected brain tissues. We further manipulated DV-induced autophagy by the inducer rapamycin and the inhibitor 3-methyladenine (3MA), which accordingly promoted or suppressed the disease symptoms and virus load in the brain of the infected mice. We demonstrated that DV2 infection of the suckling mice induces autophagy, which plays a promoting role in DV replication and pathogenesis.",2013 Sep 8,"['Lee, Ying-Ray', 'Hu, Hsuan-Yun', 'Kuo, Szu-Han', 'Lei, Huan-Yao', 'Lin, Yee-Shin', 'Yeh, Trai-Ming', 'Liu, Ching-Chuan', 'Liu, Hsiao-Sheng']",J Biomed Sci,,,False
820948b4ad6cf7e7272ef197612b1246e2117756,PMC,Dengue virus infection induces autophagy: an in vivo study,http://dx.doi.org/10.1186/1423-0127-20-65,PMC3848819,24011333,CC BY,"BACKGROUND: We and others have reported that autophagy is induced by dengue viruses (DVs) in various cell lines, and that it plays a supportive role in DV replication. This study intended to clarify whether DV infection could induce autophagy in vivo. Furthermore, the effect of DV induced autophagy on viral replication and DV-related pathogenesis was investigated. RESULTS AND CONCLUSIONS: The physiopathological parameters were evaluated after DV2 was intracranially injected into 6-day-old ICR suckling mice. Autophagy-related markers were monitored by immunohistochemical/immunofluorescent staining and Western blotting. Double-membrane autophagic vesicles were investigated by transmission-electron-microscopy. DV non-structural-protein-1 (NS1) expression (indicating DV infection) was detected in the cerebrum, medulla and midbrain of the infected mice. In these infected tissues, increased LC3 puncta formation, LC3-II expression, double-membrane autophagosome-like vesicles (autophagosome), amphisome, and decreased p62 accumulation were observed, indicating that DV2 induces the autophagic progression in vivo. Amphisome formation was demonstrated by colocalization of DV2-NS1 protein or LC3 puncta and mannose-6-phosphate receptor (MPR, endosome marker) in DV2-infected brain tissues. We further manipulated DV-induced autophagy by the inducer rapamycin and the inhibitor 3-methyladenine (3MA), which accordingly promoted or suppressed the disease symptoms and virus load in the brain of the infected mice. We demonstrated that DV2 infection of the suckling mice induces autophagy, which plays a promoting role in DV replication and pathogenesis.",2013 Sep 8,"['Lee, Ying-Ray', 'Hu, Hsuan-Yun', 'Kuo, Szu-Han', 'Lei, Huan-Yao', 'Lin, Yee-Shin', 'Yeh, Trai-Ming', 'Liu, Ching-Chuan', 'Liu, Hsiao-Sheng']",J Biomed Sci,,,False
3273d1af75cb33dbbec0d61dded9d576fe946030,PMC,Calculation of Evolutionary Correlation between Individual Genes and Full-Length Genome: A Method Useful for Choosing Phylogenetic Markers for Molecular Epidemiology,http://dx.doi.org/10.1371/journal.pone.0081106,PMC3849185,24312527,CC BY,"Individual genes or regions are still commonly used to estimate the phylogenetic relationships among viral isolates. The genomic regions that can faithfully provide assessments consistent with those predicted with full-length genome sequences would be preferable to serve as good candidates of the phylogenetic markers for molecular epidemiological studies of many viruses. Here we employed a statistical method to evaluate the evolutionary relationships between individual viral genes and full-length genomes without tree construction as a way to determine which gene can match the genome well in phylogenetic analyses. This method was performed by calculation of linear correlations between the genetic distance matrices of aligned individual gene sequences and aligned genome sequences. We applied this method to the phylogenetic analyses of porcine circovirus 2 (PCV2), measles virus (MV), hepatitis E virus (HEV) and Japanese encephalitis virus (JEV). Phylogenetic trees were constructed for comparisons and the possible factors affecting the method accuracy were also discussed in the calculations. The results revealed that this method could produce results consistent with those of previous studies about the proper consensus sequences that could be successfully used as phylogenetic markers. And our results also suggested that these evolutionary correlations could provide useful information for identifying genes that could be used effectively to infer the genetic relationships.",2013 Dec 3,"['Wang, Shuai', 'Luo, Xuenong', 'Wei, Wei', 'Zheng, Yadong', 'Dou, Yongxi', 'Cai, Xuepeng']",PLoS One,,,True
599f44a88bfd9fcd7cc5b03f3b0bf01c9b3c5ba8,PMC,Incubation periods of viral gastroenteritis: a systematic review,http://dx.doi.org/10.1186/1471-2334-13-446,PMC3849296,24066865,CC BY,"BACKGROUND: Accurate knowledge of incubation period is important to investigate and to control infectious diseases and their transmission, however statements of incubation period in the literature are often uncited, inconsistent, and/or not evidence based. METHODS: In a systematic review of the literature on five enteric viruses of public health importance, we found 256 articles with incubation period estimates, including 33 with data for pooled analysis. RESULTS: We fit a log-normal distribution to pooled data and found the median incubation period to be 4.5 days (95% CI 3.9-5.2 days) for astrovirus, 1.2 days (95% CI 1.1-1.2 days) for norovirus genogroups I and II, 1.7 days (95% CI 1.5-1.8 days) for sapovirus, and 2.0 days (95% CI 1.4-2.4 days) for rotavirus. CONCLUSIONS: Our estimates combine published data and provide sufficient quantitative detail to allow for these estimates to be used in a wide range of clinical and modeling applications. This can translate into improved prevention and control efforts in settings with transmission or the risk of transmission.",2013 Sep 25,"['Lee, Rachel M', 'Lessler, Justin', 'Lee, Rose A', 'Rudolph, Kara E', 'Reich, Nicholas G', 'Perl, Trish M', 'Cummings, Derek AT']",BMC Infect Dis,,,True
adbb0a486cf43c474df8b8b86fa6eacd422b171c,PMC,Evidence for the interaction of the human metapneumovirus G and F proteins during virus-like particle formation,http://dx.doi.org/10.1186/1743-422X-10-294,PMC3849350,24067107,CC BY,"BACKGROUND: Human metapneumovirus (HMPV) is now a major cause of lower respiratory infection in children. Although primary isolation of HMPV has been achieved in several different cell lines, the low level of virus replication and the subsequent recovery of low levels of infectious HMPV have hampered biochemical studies on the virus. These experimental methodologies usually require higher levels of biological material that can be achieved following HMPV infection. In this study we demonstrate that expression of the HMPV F, G and M proteins in mammalian cells leads to HMPV virus-like particles (VLP) formation. This experimental strategy will serve as a model system to allow the process of HMPV virus assembly to be examined. METHODS: The HMPV F, G and M proteins were expressed in mammalian cell lines. Protein cross-linking studies, sucrose gradient centrifugation and in situ imaging was used to examine interactions between the virus proteins. VLP formation was examined using sucrose density gradient centrifugation and electron microscopy analysis. RESULTS: Analysis of cells co-expressing the F, G and M proteins demonstrated that these proteins interacted. Furthermore, in cells co-expression the three HMPV proteins the formation VLPs was observed. Image analysis revealed the VLPs had a similar morphology to the filamentous virus morphology that we observed on HMPV-infected cells. The capacity of each protein to initiate VLP formation was examined using a VLP formation assay. Individual expression of each virus protein showed that the G protein was able to form VLPs in the absence of the other virus proteins. Furthermore, co-expression of the G protein with either the M or F proteins facilitated their incorporation into the VLP fraction. CONCLUSION: Co-expression of the F, G and M proteins leads to the formation of VLPs, and that incorporation of the F and M proteins into VLPs is facilitated by their interaction with the G protein. Our data suggests that the G protein plays a central role in VLP formation, and further suggests that the G protein may also play a role in the recruitment of the F and M proteins to sites of virus particle formation during HMPV infection.",2013 Sep 25,"['Loo, Liat Hui', 'Jumat, Muhammad Raihan', 'Fu, Yi', 'Ayi, Teck Choon', 'Wong, Pui San', 'Tee, Nancy WS', 'Tan, Boon Huan', 'Sugrue, Richard J']",Virol J,,,True
758c1e9d8c3cb652fe8ffc25e4b2b333cfb11ee1,PMC,Peptides Corresponding to the Predicted Heptad Repeat 2 Domain of the Feline Coronavirus Spike Protein Are Potent Inhibitors of Viral Infection,http://dx.doi.org/10.1371/journal.pone.0082081,PMC3849439,24312629,CC BY,"BACKGROUND: Feline infectious peritonitis (FIP) is a lethal immune-mediated disease caused by feline coronavirus (FCoV). Currently, no therapy with proven efficacy is available. In searching for agents that may prove clinically effective against FCoV infection, five analogous overlapping peptides were designed and synthesized based on the putative heptad repeat 2 (HR2) sequence of the spike protein of FCoV, and the antiviral efficacy was evaluated. METHODS: Plaque reduction assay and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cytotoxicity assay were performed in this study. Peptides were selected using a plaque reduction assay to inhibit Feline coronavirus infection. RESULTS: The results demonstrated that peptide (FP5) at concentrations below 20 μM inhibited viral replication by up to 97%. The peptide (FP5) exhibiting the most effective antiviral effect was further combined with a known anti-viral agent, human interferon-α (IFN-α), and a significant synergistic antiviral effect was observed. CONCLUSION: Our data suggest that the synthetic peptide FP5 could serve as a valuable addition to the current FIP prevention methods.",2013 Dec 3,"['Liu, I-Jung', 'Tsai, Wan-Ting', 'Hsieh, Li-En', 'Chueh, Ling-Ling']",PLoS One,,,True
a986a6d115df1e271c89a765800aa931ac3f6833,PMC,An evaluation of the global network of field epidemiology and laboratory training programmes: a resource for improving public health capacity and increasing the number of public health professionals worldwide,http://dx.doi.org/10.1186/1478-4491-11-45,PMC3849587,24053689,CC BY,"BACKGROUND: Given that many infectious diseases spread rapidly, across borders and species, there is a growing worldwide need to increase the number of public health professionals skilled in controlling infectious epidemics. Needed also are more public health professionals skilled in non-communicable disease surveillance and interventions. As a result, we surveyed all 57 field epidemiology training programmes (FETPs) that are members of the Training Program in Epidemiology and Public Health Interventions Network (TEPHINET), to evaluate the progress of the FETPs, the only global applied epidemiology network, toward increasing public health capacity globally. METHODS: Data on the FETP programmes and the training they provide were abstracted from TEPHINET membership surveys and verified with FETP directors for all FETPs that were members of TEPHINET in 2012. Data on abstracts submitted to the recent TEPHINET Global Scientific Conference, on recent accomplishments by each FETP, and on quality improvement were also compiled to provide a worldwide view of the public health human resource capacity produced by these programmes. RESULTS: A total of 6980 public health professionals worldwide have graduated from an FETP or from the Center for Disease Control and Prevention’s Epidemiology Intelligence Service (EIS). FETP residents and graduates participate in key public health prevention, control, and response activities. Each FETP has adapted its curriculum and objectives over time to align with its country’s public health priorities. FETPs are well integrated into their national public health infrastructures, and they have many partners at the national, regional and global levels. CONCLUSION: FETPs are a competent and diverse source of highly skilled public health professionals who contribute significantly to public health’s global human resource needs. This finding is evidenced by 1) the training curricula that were adapted over time to meet public health’s human resource needs, 2) the FETPs’ continued support from internal and external partners, 3) the increasing number of FETP residents and graduates and their increasing contribution to effective public health work, and 4) the increased quality improvement initiatives facilitated through the FETPs membership in one global network, TEPHINET.",2013 Sep 21,"['Subramanian, Renee E', 'Herrera, Dionisio G', 'Kelly, Paul M']",Hum Resour Health,,,True
2558f92b15a62a49fdd0e7621ba97f1a4aa0080d,PMC,The first detection of influenza in the Finnish pig population: a retrospective study,http://dx.doi.org/10.1186/1751-0147-55-69,PMC3850993,24047612,CC BY,"BACKGROUND: Swine influenza is an infectious acute respiratory disease of pigs caused by influenza A virus. We investigated the time of entry of swine influenza into the Finnish pig population. We also describe the molecular detection of two types of influenza A (H1N1) viruses in porcine samples submitted in 2009 and 2010. This retrospective study was based on three categories of samples: blood samples collected for disease monitoring from pigs at major slaughterhouses from 2007 to 2009; blood samples from pigs in farms with a special health status taken in 2008 and 2009; and diagnostic blood samples from pigs in farms with clinical signs of respiratory disease in 2008 and 2009. The blood samples were tested for influenza A antibodies with an antibody ELISA. Positive samples were further analyzed for H1N1, H3N2, and H1N2 antibodies with a hemagglutination inhibition test. Diagnostic samples for virus detection were subjected to influenza A M-gene-specific real-time RT-PCR and to pandemic influenza A H1N1-specific real-time RT-PCR. Positive samples were further analyzed with RT-PCRs designed for this purpose, and the PCR products were sequenced and sequences analyzed phylogenetically. RESULTS: In the blood samples from pigs in special health class farms producing replacement animals and in diagnostic blood samples, the first serologically positive samples originated from the period July–August 2008. In samples collected for disease monitoring, < 0.1%, 0% and 16% were positive for antibodies against influenza A H1N1 in the HI test in 2007, 2008, and 2009, respectively. Swine influenza A virus of avian-like H1N1 was first detected in diagnostic samples in February 2009. In 2009 and 2010, the avian-like H1N1 virus was detected on 12 and two farms, respectively. The pandemic H1N1 virus (A(H1N1)pdm09) was detected on one pig farm in 2009 and on two farms in 2010. CONCLUSIONS: Based on our study, swine influenza of avian-like H1N1 virus was introduced into the Finnish pig population in 2008 and A(H1N1)pdm09 virus in 2009. The source of avian-like H1N1 infection could not be determined. Cases of pandemic H1N1 in pigs coincided with the period when the A(H1N1)pdm09 virus was spread in humans in Finland.",2013 Sep 18,"['Nokireki, Tiina', 'Laine, Taina', 'London, Laura', 'Ikonen, Niina', 'Huovilainen, Anita']",Acta Vet Scand,,,True
55844fc8a5cb75ffa1a249436ad30d6d93792df5,PMC,"Transmission potential of influenza A/H7N9, February to May 2013, China",http://dx.doi.org/10.1186/1741-7015-11-214,PMC3851127,24083506,CC BY,"BACKGROUND: On 31 March 2013, the first human infections with the novel influenza A/H7N9 virus were reported in Eastern China. The outbreak expanded rapidly in geographic scope and size, with a total of 132 laboratory-confirmed cases reported by 3 June 2013, in 10 Chinese provinces and Taiwan. The incidence of A/H7N9 cases has stalled in recent weeks, presumably as a consequence of live bird market closures in the most heavily affected areas. Here we compare the transmission potential of influenza A/H7N9 with that of other emerging pathogens and evaluate the impact of intervention measures in an effort to guide pandemic preparedness. METHODS: We used a Bayesian approach combined with a SEIR (Susceptible-Exposed-Infectious-Removed) transmission model fitted to daily case data to assess the reproduction number (R) of A/H7N9 by province and to evaluate the impact of live bird market closures in April and May 2013. Simulation studies helped quantify the performance of our approach in the context of an emerging pathogen, where human-to-human transmission is limited and most cases arise from spillover events. We also used alternative approaches to estimate R based on individual-level information on prior exposure and compared the transmission potential of influenza A/H7N9 with that of other recent zoonoses. RESULTS: Estimates of R for the A/H7N9 outbreak were below the epidemic threshold required for sustained human-to-human transmission and remained near 0.1 throughout the study period, with broad 95% credible intervals by the Bayesian method (0.01 to 0.49). The Bayesian estimation approach was dominated by the prior distribution, however, due to relatively little information contained in the case data. We observe a statistically significant deceleration in growth rate after 6 April 2013, which is consistent with a reduction in A/H7N9 transmission associated with the preemptive closure of live bird markets. Although confidence intervals are broad, the estimated transmission potential of A/H7N9 appears lower than that of recent zoonotic threats, including avian influenza A/H5N1, swine influenza H3N2sw and Nipah virus. CONCLUSION: Although uncertainty remains high in R estimates for H7N9 due to limited epidemiological information, all available evidence points to a low transmission potential. Continued monitoring of the transmission potential of A/H7N9 is critical in the coming months as intervention measures may be relaxed and seasonal factors could promote disease transmission in colder months.",2013 Oct 2,"['Chowell, Gerardo', 'Simonsen, Lone', 'Towers, Sherry', 'Miller, Mark A', 'Viboud, Cécile']",BMC Med,,,True
257d3ac44f72e298b1b0c5f46561948b973ac3d5,PMC,Different virulence of porcine and porcine-like bovine rotavirus strains with genetically nearly identical genomes in piglets and calves,http://dx.doi.org/10.1186/1297-9716-44-88,PMC3851489,24083947,CC BY,"Direct interspecies transmissions of group A rotaviruses (RVA) have been reported under natural conditions. However, the pathogenicity of RVA has never been directly compared in homologous and heterologous hosts. The bovine RVA/Cow-tc/KOR/K5/2004/G5P[7] strain, which was shown to possess a typical porcine-like genotype constellation similar to that of the G5P[7] prototype RVA/Pig-tc/USA/OSU/1977/G5P9[7] strain, was examined for its pathogenicity and compared with the porcine G5P[7] RVA/Pig-tc/KOR/K71/2006/G5P[7] strain possessing the same genotype constellation. The bovine K5 strain induced diarrhea and histopathological changes in the small intestine of piglets and calves, whereas the porcine K71 strain caused diarrhea and histopathological changes in the small intestine of piglets, but not in calves. Furthermore, the bovine K5 strain showed extra-intestinal tropisms in both piglets and calves, whereas the porcine K71 strain had extra-intestinal tropisms in piglets, but not in calves. Therefore, we performed comparative genomic analysis of the K71 and K5 RVA strains to determine whether specific mutations could be associated with these distinct clinical and pathological phenotypes. Full-length sequencing analyses for the 11 genomic segments for K71 and K5 revealed that these strains were genetically nearly identical to each other. Two nucleotide mutations were found in the 5′ untranslated region (UTR) of NSP5 and the 3′ UTR of NSP3, and eight amino acid mutations in VP1-VP4 and NSP2. Some of these mutations may be critical molecular determinants for RVA virulence and/or pathogenicity.",2013 Oct 1,"['Park, Jun-Gyu', 'Kim, Hyun-Jeong', 'Matthijnssens, Jelle', 'Alfajaro, Mia Madel', 'Kim, Deok-Song', 'Son, Kyu-Yeol', 'Kwon, Hyoung-Jun', 'Hosmillo, Myra', 'Ryu, Eun-Hye', 'Kim, Ji-Yun', 'Cena, Rohani B', 'Lee, Ju-Hwan', 'Kang, Mun-Il', 'Park, Sang-Ik', 'Cho, Kyoung-Oh']",Vet Res,,,True
fda3a715b0db3802a398fdadcf819448672b339a,PMC,Different virulence of porcine and porcine-like bovine rotavirus strains with genetically nearly identical genomes in piglets and calves,http://dx.doi.org/10.1186/1297-9716-44-88,PMC3851489,24083947,CC BY,"Direct interspecies transmissions of group A rotaviruses (RVA) have been reported under natural conditions. However, the pathogenicity of RVA has never been directly compared in homologous and heterologous hosts. The bovine RVA/Cow-tc/KOR/K5/2004/G5P[7] strain, which was shown to possess a typical porcine-like genotype constellation similar to that of the G5P[7] prototype RVA/Pig-tc/USA/OSU/1977/G5P9[7] strain, was examined for its pathogenicity and compared with the porcine G5P[7] RVA/Pig-tc/KOR/K71/2006/G5P[7] strain possessing the same genotype constellation. The bovine K5 strain induced diarrhea and histopathological changes in the small intestine of piglets and calves, whereas the porcine K71 strain caused diarrhea and histopathological changes in the small intestine of piglets, but not in calves. Furthermore, the bovine K5 strain showed extra-intestinal tropisms in both piglets and calves, whereas the porcine K71 strain had extra-intestinal tropisms in piglets, but not in calves. Therefore, we performed comparative genomic analysis of the K71 and K5 RVA strains to determine whether specific mutations could be associated with these distinct clinical and pathological phenotypes. Full-length sequencing analyses for the 11 genomic segments for K71 and K5 revealed that these strains were genetically nearly identical to each other. Two nucleotide mutations were found in the 5′ untranslated region (UTR) of NSP5 and the 3′ UTR of NSP3, and eight amino acid mutations in VP1-VP4 and NSP2. Some of these mutations may be critical molecular determinants for RVA virulence and/or pathogenicity.",2013 Oct 1,"['Park, Jun-Gyu', 'Kim, Hyun-Jeong', 'Matthijnssens, Jelle', 'Alfajaro, Mia Madel', 'Kim, Deok-Song', 'Son, Kyu-Yeol', 'Kwon, Hyoung-Jun', 'Hosmillo, Myra', 'Ryu, Eun-Hye', 'Kim, Ji-Yun', 'Cena, Rohani B', 'Lee, Ju-Hwan', 'Kang, Mun-Il', 'Park, Sang-Ik', 'Cho, Kyoung-Oh']",Vet Res,,,False
e1400d2059ba0e337608df70a17351ee9c3caa17,PMC,Genetic and biological characterisation of an avian-like H1N2 swine influenza virus generated by reassortment of circulating avian-like H1N1 and H3N2 subtypes in Denmark,http://dx.doi.org/10.1186/1743-422X-10-290,PMC3851529,24047399,CC BY,"BACKGROUND: The influenza A virus subtypes H1N1, H1N2 and H3N2 are the most prevalent subtypes in swine. In 2003, a reassorted H1N2 swine influenza virus (SIV) subtype appeared and became prevalent in Denmark. In the present study, the reassortant H1N2 subtype was characterised genetically and the infection dynamics compared to an “avian-like” H1N1 virus by an experimental infection study. METHODS: Sequence analyses were performed of the H1N2 virus. Two groups of pigs were inoculated with the reassortant H1N2 virus and an “avian-like” H1N1 virus, respectively, followed by inoculation with the opposite subtype four weeks later. Measurements of HI antibodies and acute phase proteins were performed. Nasal virus excretion and virus load in lungs were determined by real-time RT-PCR. RESULTS: The phylogenetic analysis revealed that the reassorted H1N2 virus contained a European “avian-like” H1-gene and a European “swine-like” N2-gene, thus being genetically distinct from most H1N2 viruses circulating in Europe, but similar to viruses reported in 2009/2010 in Sweden and Italy. Sequence analyses of the internal genes revealed that the reassortment probably arose between circulating Danish “avian-like” H1N1 and H3N2 SIVs. Infected pigs developed cross-reactive antibodies, and increased levels of acute phase proteins after inoculations. Pigs inoculated with H1N2 exhibited nasal virus excretion for seven days, peaking day 1 after inoculation two days earlier than H1N1 infected pigs and at a six times higher level. The difference, however, was not statistically significant. Pigs euthanized on day 4 after inoculation, had a high virus load in all lung lobes. After the second inoculation, the nasal virus excretion was minimal. There were no clinical sign except elevated body temperature under the experimental conditions. CONCLUSIONS: The “avian-like” H1N2 subtype, which has been established in the Danish pig population at least since 2003, is a reassortant between circulating swine “avian-like” H1N1 and H3N2. The Danish H1N2 has an “avian-like” H1 and differs from most other reported H1N2 viruses in Europe and North America/Asia, which have H1-genes of human or “classical-swine” origin, respectively. The variant seems, however, also to be circulating in countries like Sweden and Italy. The infection dynamics of the reassorted “avian-like” H1N2 is similar to the older “avian-like” H1N1 subtype.",2013 Sep 18,"['Trebbien, Ramona', 'Bragstad, Karoline', 'Larsen, Lars Erik', 'Nielsen, Jens', 'Bøtner, Anette', 'Heegaard, Peter MH', 'Fomsgaard, Anders', 'Viuff, Birgitte', 'Hjulsager, Charlotte Kristiane']",Virol J,,,True
6360e58e9bb14d3e03b5c78025509ea6f9482bec,PMC,Selection of reference genes for quantitative real-time PCR analysis in chicken embryo fibroblasts infected with avian leukosis virus subgroup J,http://dx.doi.org/10.1186/1756-0500-6-402,PMC3851545,24099561,CC BY,"BACKGROUND: The selection of stably expressed reference genes is a prerequisite when evaluating gene expression, via real-time PCR, in cells in response to viral infections. The objective of our study was to identify suitable reference genes for mRNA expression analysis in chicken embryonic fibroblasts (CEF) after infection with avian leukosis virus subgroup J (ALV-J). FINDINGS: The expression levels of 11 potential reference genes in CEF infected with ALV-J were determined by real-time PCR. The expression stability of these genes were analyzed and ranked using the geNorm tool. Analysis indicated that the genes RPL30 (ribosomal protein L30) and SDHA (succinate dehydrogenase complex, subunit A) were the most stably expressed genes in the ALV-J infected CEF. CONCLUSIONS: The RPL30 and SDHA were deemed suitable for use as reference genes for real-time PCR analysis of mRNA gene expression during ALV-J infection, whereas commonly used ACTB and GAPDH are unsuitable to be reference genes.",2013 Oct 7,"['Yang, Falong', 'Lei, Xiaowen', 'Rodriguez-Palacios, Alexander', 'Tang, Cheng', 'Yue, Hua']",BMC Res Notes,,,True
d4c35983add63a4f8eee72b1d8fa864de4147ead,PMC,A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines,http://dx.doi.org/10.1371/journal.pone.0081587,PMC3852489,24324708,CC BY,"An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367–606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients’ lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection.",2013 Dec 4,"['Du, Lanying', 'Kou, Zhihua', 'Ma, Cuiqing', 'Tao, Xinrong', 'Wang, Lili', 'Zhao, Guangyu', 'Chen, Yaoqing', 'Yu, Fei', 'Tseng, Chien-Te K.', 'Zhou, Yusen', 'Jiang, Shibo']",PLoS One,,,True
aa1eaad52d7a7827850cecf3d6b582e728e7e543,PMC,Haemorrhagic pneumonia in sled dogs caused by Streptococcus equi subsp. zooepidemicus - one fatality and two full recoveries: a case report,http://dx.doi.org/10.1186/1751-0147-55-67,PMC3852515,24020788,CC BY,"In spite of yearly vaccination, outbreaks of canine infectious respiratory disease are periodically seen amongst domestic dogs. These infections compromise host defense mechanisms, and, when combined with other stressful events, allow opportunistic pathogens like Streptococcus equi subsp. zooepidemicus to create serious disease. Early recognition and treatment are tremendously important for a successful outcome in these cases. A polyvalent vaccine was given to 22 racing dogs three days after a competition, followed by two days of rest, and then the dogs were returned to regular training. Coughing was noticed among the dogs four days after immunisation. Three days after this outbreak one of the dogs was unusually silent and was found dead the next morning. Simultaneously two other dogs developed haemorrhagic expectorate, depression and dyspnea and were brought in to the veterinary hospital. Streptococcus equi subsp. zooepidemicus was isolated in pure culture from all three cases. They were treated and rehabilitated successfully, and won a sledge race three months later. This paper discusses the necropsy results, treatment regime, rehabilitation and the chronology of vaccination, stressful events and disease.",2013 Sep 11,"['Jaeger, Gry', 'Skogmo, Hege Kippenes', 'Kolbjørnsen, Øyvor', 'Larsen, Hans Jørgen Søiland', 'Bergsjø, Bjarne', 'Sørum, Henning']",Acta Vet Scand,,,True
096d707e74acc27426416dacf89d5d134a0b9866,PMC,Immunosuppression of the Trimellitic Anhydride-Induced Th2 Response by Novel Nonanatural Products Mixture in Mice,http://dx.doi.org/10.1155/2013/748123,PMC3852580,24348718,CC BY,"Many natural dietary products prevent or cure allergic inflammation; however, the ability of mixtures of these natural medicinals to suppress allergic skin inflammation is unknown. We examined the inhibitory effects of nonanatural products mixture (NPM-9), which provides immunoregulatory activation, on Th2-mediated skin allergic inflammation. Oral administration of NPM-9 in mice reduced ear thickness and specific IgE production in trimellitic anhydride- (TMA-)induced contact hypersensitivity (CHS). NPM-9 also suppressed IL-4 and IL-1β production in splenocytes but prevented only TMA-induced IL-1β production in inflamed ears. To characterize the mechanism of this effect, we examined NPM-9 immunosuppression on an OVA-induced Th2 allergic state. Oral administration of NPM-9 inhibited Th2-mediated serum IgE overproduction. NPM-9 also downregulated the polarized Th2 response, whereas it upregulated Th1 response in splenocytes. These data suggest that NPM-9 may be a useful therapeutic agent for allergic inflammatory diseases through its suppression of the Th2-mediated allergic response.",2013 Nov 19,"['Bae, Min-Jung', 'Shin, Hee Soon', 'Shon, Dong-Hwa']",Evid Based Complement Alternat Med,,,True
2a46fb28bde7f183808bb47ec90ffd8d97511a73,PMC,"Microbiological, pathological and histological findings in four Danish pig herds affected by a new neonatal diarrhoea syndrome",http://dx.doi.org/10.1186/1746-6148-9-206,PMC3852778,24119974,CC BY,"BACKGROUND: Neonatal diarrhoea is a frequent clinical condition in commercial swine herds, previously regarded to be uncomplicated to treat. However, since 2008 it seems that a new neonatal diarrhoeic syndrome unresponsive to antibiotics and common management practices has emerged. Routine laboratory examinations have not detected any pathogen related to this syndrome. The primary purpose of this study was to evaluate if well-known enteric pathogens could be associated with outbreaks of neonatal diarrhoea, thus question the hypotheses of a new syndrome. Furthermore, we wanted to evaluate macroscopic and microscopic findings associated with these outbreaks and if possible propose a preliminary piglet-level case-definition on syndrome New Neonatal Porcine Diarrhoea syndrome (NNPDS). RESULTS: Four well-managed herds experiencing neonatal diarrhoea with no previously established laboratory conclusion and suspected to suffer from New Neonatal Porcine Diarrhoea Syndrome, were selected. Within these herds, 51 diarrhoeic and 50 non-diarrhoeic piglets at the age of three to seven days were necropsied and subjected to histological and microbiological examination. Faeces were non-haemorrhagic. Neither enterotoxigenic E. coli, Clostridium perfringens type A or C, Clostridium difficile, rotavirus, coronavirus, Cryptosporidium spp, Giardia spp, Cystoisospora suis nor Strongyloides ransomi were associated with diarrhoea in the investigated outbreaks. Macroscopically, the diarrhoeic piglets were characterized by filled stomachs and flaccid intestines without mucosal changes. The predominant histological lesions were villous atrophy in jejunum and ileum. Epithelial lesions in colon were seen in one third of the case piglets. CONCLUSIONS: The results of the study supported the hypothesis that a new neonatal porcine diarrhoea was present in the investigated herds, since no known pathogen(s) or management factors could explain the diarrhoeal outbreaks. Based on the findings in the four herds the following case-definition of NNPDS was suggested: Non-haemorrhagic diarrhoea during the first week of life, without detection of known infectious pathogens, characterized by milk-filled stomachs and flaccid intestines at necropsy.",2013 Oct 12,"['Kongsted, Hanne', 'Jonach, Beata', 'Haugegaard, Svend', 'Angen, Øystein', 'Jorsal, Sven E', 'Kokotovic, Branko', 'Larsen, Lars E', 'Jensen, Tim K', 'Nielsen, Jens P']",BMC Vet Res,,,True
5a2360e93ec038502133c97cf78a114c012e5df4,PMC,Whole genome methylation array analysis reveals new aspects in Balkan endemic nephropathy etiology,http://dx.doi.org/10.1186/1471-2369-14-225,PMC3852817,24131581,CC BY,"BACKGROUND: Balkan endemic nephropathy (BEN) represents a chronic progressive interstitial nephritis in striking correlation with uroepithelial tumours of the upper urinary tract. The disease has endemic distribution in the Danube river regions in several Balkan countries. DNA methylation is a primary epigenetic modification that is involved in major processes such as cancer, genomic imprinting, gene silencing, etc. The significance of CpG island methylation status in normal development, cell differentiation and gene expression is widely recognized, although still stays poorly understood. METHODS: We performed whole genome DNA methylation array analysis on DNA pool samples from peripheral blood from 159 affected individuals and 170 healthy individuals. This technique allowed us to determine the methylation status of 27 627 CpG islands throughout the whole genome in healthy controls and BEN patients. Thus we obtained the methylation profile of BEN patients from Bulgarian and Serbian endemic regions. RESULTS: Using specifically developed software we compared the methylation profiles of BEN patients and corresponding controls and revealed the differently methylated regions. We then compared the DMRs between all patient-control pairs to determine common changes in the epigenetic profiles. SEC61G, IL17RA, HDAC11 proved to be differently methylated throughout all patient-control pairs. The CpG islands of all 3 genes were hypomethylated compared to controls. This suggests that dysregulation of these genes involved in immunological response could be a common mechanism in BEN pathogenesis in both endemic regions and in both genders. CONCLUSION: Our data propose a new hypothesis that immunologic dysregulation has a place in BEN etiopathogenesis.",2013 Oct 16,"['Staneva, Rada', 'Rukova, Blaga', 'Hadjidekova, Savina', 'Nesheva, Desislava', 'Antonova, Olga', 'Dimitrov, Plamen', 'Simeonov, Valeri', 'Stamenov, Georgi', 'Cukuranovic, Rade', 'Cukuranovic, Jovana', 'Stefanovic, Vladislav', 'Polenakovic, Momir', 'Dimova, Ivanka', 'Hlushchuk, Ruslan', 'Djonov, Valentin', 'Galabov, Angel', 'Toncheva, Draga']",BMC Nephrol,,,True
588ad9cd788e0631c93e4164f98489d9b3f30811,PMC,Adaptive evolution of bat dipeptidyl peptidase 4 (dpp4): implications for the origin and emergence of Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1186/1743-422X-10-304,PMC3852826,24107353,CC BY,"BACKGROUND: The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) that first appeared in Saudi Arabia during the summer of 2012 has to date (20th September 2013) caused 58 human deaths. MERS-CoV utilizes the dipeptidyl peptidase 4 (DPP4) host cell receptor, and analysis of the long-term interaction between virus and receptor provides key information on the evolutionary events that lead to the viral emergence. FINDINGS: We show that bat DPP4 genes have been subject to significant adaptive evolution, suggestive of a long-term arms-race between bats and MERS related CoVs. In particular, we identify three positively selected residues in DPP4 that directly interact with the viral surface glycoprotein. CONCLUSIONS: Our study suggests that the evolutionary lineage leading to MERS-CoV may have circulated in bats for a substantial time period.",2013 Oct 10,"['Cui, Jie', 'Eden, John-Sebastian', 'Holmes, Edward C', 'Wang, Lin-Fa']",Virol J,,,True
fb0191a305e3289b1be275259659e20b096247b5,PMC,SSW Library: An SIMD Smith-Waterman C/C++ Library for Use in Genomic Applications,http://dx.doi.org/10.1371/journal.pone.0082138,PMC3852983,24324759,CC BY,"BACKGROUND: The Smith-Waterman algorithm, which produces the optimal pairwise alignment between two sequences, is frequently used as a key component of fast heuristic read mapping and variation detection tools for next-generation sequencing data. Though various fast Smith-Waterman implementations are developed, they are either designed as monolithic protein database searching tools, which do not return detailed alignment, or are embedded into other tools. These issues make reusing these efficient Smith-Waterman implementations impractical. RESULTS: To facilitate easy integration of the fast Single-Instruction-Multiple-Data Smith-Waterman algorithm into third-party software, we wrote a C/C++ library, which extends Farrar’s Striped Smith-Waterman (SSW) to return alignment information in addition to the optimal Smith-Waterman score. In this library we developed a new method to generate the full optimal alignment results and a suboptimal score in linear space at little cost of efficiency. This improvement makes the fast Single-Instruction-Multiple-Data Smith-Waterman become really useful in genomic applications. SSW is available both as a C/C++ software library, as well as a stand-alone alignment tool at: https://github.com/mengyao/Complete-Striped-Smith-Waterman-Library. CONCLUSIONS: The SSW library has been used in the primary read mapping tool MOSAIK, the split-read mapping program SCISSORS, the MEI detector TANGRAM, and the read-overlap graph generation program RZMBLR. The speeds of the mentioned software are improved significantly by replacing their ordinary Smith-Waterman or banded Smith-Waterman module with the SSW Library.",2013 Dec 4,"['Zhao, Mengyao', 'Lee, Wan-Ping', 'Garrison, Erik P.', 'Marth, Gabor T.']",PLoS One,,,True
864336d3d1a34686efdd078534a092fc888c2c3f,PMC,Agent based modeling of Treg-Teff cross regulation in relapsing-remitting multiple sclerosis,http://dx.doi.org/10.1186/1471-2105-14-S16-S9,PMC3853330,24564794,CC BY,BACKGROUND: Multiple sclerosis (MS) is a disease of central nervous system that causes the removal of fatty myelin sheath from axons of the brain and spinal cord. Autoimmunity plays an important role in this pathology outcome and body's own immune system attacks on the myelin sheath causing the damage. The etiology of the disease is partially understood and the response to treatment cannot easily be predicted. RESULTS: We presented the results obtained using 8 genetically predisposed randomly chosen individuals reproducing both the absence and presence of malfunctions of the Teff-Treg cross-balancing mechanisms at a local level. For simulating the absence of a local malfunction we supposed that both Teff and Treg populations had similar maximum duplication rates. Results presented here suggest that presence of a genetic predisposition is not always a sufficient condition for developing the disease. Other conditions such as a breakdown of the mechanisms that regulate and allow peripheral tolerance should be involved. CONCLUSIONS: The presented model allows to capture the essential dynamics of relapsing-remitting MS despite its simplicity. It gave useful insights that support the hypothesis of a breakdown of Teff-Treg cross balancing mechanisms.,2013 Oct 22,"['Pennisi, Marzio', 'Rajput, Abdul-Mateen', 'Toldo, Luca', 'Pappalardo, Francesco']",BMC Bioinformatics,,,True
2f4331d2427906e96afeb82ef5c4a90dda236470,PMC,Anti HSV-1 Activity of Halistanol Sulfate and Halistanol Sulfate C Isolated from Brazilian Marine Sponge Petromica citrina (Demospongiae),http://dx.doi.org/10.3390/md11114176,PMC3853722,24172213,CC BY,"The n-butanol fraction (BF) obtained from the crude extract of the marine sponge Petromica citrina, the halistanol-enriched fraction (TSH fraction), and the isolated compounds halistanol sulfate (1) and halistanol sulfate C (2), were evaluated for their inhibitory effects on the replication of the Herpes Simplex Virus type 1 (HSV-1, KOS strain) by the viral plaque number reduction assay. The TSH fraction was the most effective against HSV-1 replication (SI = 15.33), whereas compounds 1 (SI = 2.46) and 2 (SI = 1.95) were less active. The most active fraction and these compounds were also assayed to determine the viral multiplication step(s) upon which they act as well as their potential synergistic effects. The anti-HSV-1 activity detected was mediated by the inhibition of virus attachment and by the penetration into Vero cells, the virucidal effect on virus particles, and by the impairment in levels of ICP27 and gD proteins of HSV-1. In summary, these results suggest that the anti-HSV-1 activity of TSH fraction detected is possibly related to the synergic effects of compounds 1 and 2.",2013 Oct 29,"['da Rosa Guimarães, Tatiana', 'Quiroz, Carlos Guillermo', 'Rigotto, Caroline', 'de Oliveira, Simone Quintana', 'Rojo de Almeida, Maria Tereza', 'Bianco, Éverson Miguel', 'Moritz, Maria Izabel Goulart', 'Carraro, João Luís', 'Palermo, Jorge Alejandro', 'Cabrera, Gabriela', 'Schenkel, Eloir Paulo', 'Reginatto, Flávio Henrique', 'Oliveira Simões, Cláudia Maria']",Mar Drugs,,,True
f53604d28e212733384d7ec28e84d4a62e506254,PMC,Serological Evidence for Multiple Strains of Canine Norovirus in the UK Dog Population,http://dx.doi.org/10.1371/journal.pone.0081596,PMC3855277,24339947,CC BY,"Noroviruses are associated with intestinal disease in humans, cows, pigs, mice, and, more recently, dogs. In 2007, the first canine norovirus (CNV) was identified and characterized in Italy. Subsequent studies have identified CNV in stools of dogs from Portugal, Greece, and the United States. To investigate the prevalence of CNV in the UK dog population, 228 canine stool samples were screened for CNV by qPCR, and 396 serum samples were screened for anti-CNV antibodies. qPCR of RNA extracted from canine stool samples did not reveal any CNV-positive samples, based on samples collected from diarrhoeic and control dogs in 2012–2013. CNV virus-like particles to three different CNV strains were produced using recombinant baculoviruses and a seroprevalence screen undertaken. Anti-CNV antibodies were identified at significant levels in canine serum; 38.1% of samples collected between 1999–2001 and 60.1% of samples collected in 2012–2013 were seropositive. The increase in seroprevalence over time (p<0.001) suggests that the CNV strains screened for are becoming more widespread. Variation in seroprevalence to different CNV strains was also identified. Two-thirds of the dogs were seropositive to a single strain, whereas the remaining third were seropositive to two or three of the strains analysed. This study has provided the first evidence that CNV is present in the UK, with seroprevalence identified to multiple circulating strains. This warrants further study and increased awareness of this recently discovered canine virus.",2013 Dec 5,"['Caddy, Sarah', 'Emmott, Edward', 'El-Attar, Laila', 'Mitchell, Judy', 'de Rougemont, Alexis', 'Brownlie, Joe', 'Goodfellow, Ian']",PLoS One,,,True
6e1a04ccbbb614c9a28dd37899d7537f907028a8,PMC,Cytoplasmic Viruses: Rage against the (Cellular RNA Decay) Machine,http://dx.doi.org/10.1371/journal.ppat.1003762,PMC3855480,24339774,CC BY,,2013 Dec 5,"['Moon, Stephanie L.', 'Wilusz, Jeffrey']",PLoS Pathog,,,True
394b9e259a4a871f49e3ab9209a05059fb6347ed,PMC,A Multigene Approach for Comparing Genealogy of Betacoronavirus from Cattle and Horses,http://dx.doi.org/10.1155/2013/349702,PMC3855977,24348152,CC BY,"Gastroenteritis is one of the leading causes of morbidity and mortality among young and newborn animals and is often caused by multiple intestinal infections, with rotavirus and bovine coronavirus (BCoV) being the main viral causes in cattle. Given that BCoV is better studied than equine coronaviruses and given the possibility of interspecies transmission of these viruses, this research was designed to compare the partial sequences of the spike glycoprotein (S), hemagglutinin-esterase protein (HE), and nucleoprotein (N) genes from coronaviruses from adult cattle with winter dysentery, calves with neonatal diarrhea, and horses. To achieve this, eleven fecal samples from dairy cows with winter dysentery, three from calves, and two from horses, all from Brazil, were analysed. It could be concluded that the enteric BCoV genealogy from newborn and adult cattle is directly associated with geographic distribution patterns, when S and HE genes are taken into account. A less-resolved genealogy exists for the HE and N genes in cattle, with a trend for an age-related segregation pattern. The coronavirus strains from horses revealed Betacoronavirus sequences indistinguishable from those found in cattle, a fact previously unknown.",2013 Nov 17,"['Barros, Iracema N.', 'Silva, Sheila O. S.', 'Nogueira Neto, Francisco S.', 'Asano, Karen M.', 'Souza, Sibele P.', 'Richtzenhain, Leonardo J.', 'Brandao, Paulo E.']",ScientificWorldJournal,,,True
cc61245f0f1817ac5d96a0cf9bce41377d6e4978,PMC,Detection of Coronaviruses in Bats of Various Species in Italy,http://dx.doi.org/10.3390/v5112679,PMC3856409,24184965,CC BY,"Bats are natural reservoirs for many mammalian coronaviruses, which have received renewed interest after the discovery of the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) CoV in humans. This study describes the identification and molecular characterization of alphacoronaviruses and betacoronaviruses in bats in Italy, from 2010 to 2012. Sixty-nine faecal samples and 126 carcasses were tested using pan-coronavirus RT-PCR. Coronavirus RNAs were detected in seven faecal samples and nine carcasses. A phylogenetic analysis of RNA-dependent RNA polymerase sequence fragments aided in identifying two alphacoronaviruses from Kuhl’s pipistrelle (Pipistrellus kuhlii), three clade 2b betacoronaviruses from lesser horseshoe bats (Rhinolophus hipposideros), and 10 clade 2c betacoronaviruses from Kuhl’s pipistrelle, common noctule (Nyctalus noctula), and Savi’s pipistrelle (Hypsugo savii). This study fills a substantive gap in the knowledge on bat-CoV ecology in Italy, and extends the current knowledge on clade 2c betacoronaviruses with new sequences obtained from bats that have not been previously described as hosts of these viruses.",2013 Oct 31,"['Lelli, Davide', 'Papetti, Alice', 'Sabelli, Cristiano', 'Rosti, Enrica', 'Moreno, Ana', 'Boniotti, Maria B.']",Viruses,,,True
2c5983eedfe4431e007a45dcf0103176ed1d9ff8,PMC,Identification of Three Antiviral Inhibitors against Japanese Encephalitis Virus from Library of Pharmacologically Active Compounds 1280,http://dx.doi.org/10.1371/journal.pone.0078425,PMC3857149,24348901,CC BY,"Japanese encephalitis virus (JEV) can cause severe central nervous disease with a high mortality rate. There is no antiviral drug available for JEV-specific treatment. In this study, a cytopathic-effect-based, high-throughput screening assay was developed and applied to screen JEV inhibitors from Library of Pharmacologically Active Compounds 1280. The antiviral effects of three hit compounds including FGIN-1-27, cilnidipine, and niclosamide were evaluated in cells by western blotting, indirect immunofluorescence assay, and plaque reduction assay. A time-of-addition assay proved that all three compounds inhibited JEV at the stage of replication. The EC50s of FGIN-1-27, cilnidipine, and niclosamide were 3.21, 6.52, and 5.80 µM, respectively, while the selectivity indexes were 38.79, 30.67, and 7.49. FGIN-1-27 and cilnidipine have high efficiency and selectivity against JEV. This study provided two JEV antiviral inhibitors as candidates for treatment of JEV infection.",2013 Nov 4,"[""Fang, Jin'e"", 'Sun, Leqiang', 'Peng, Guiqing', 'Xu, Jia', 'Zhou, Rui', 'Cao, Shengbo', 'Chen, Huanchun', 'Song, Yunfeng']",PLoS One,,,True
4070000cd4a0880ff387df1d1a42f5f45f34e015,PMC,Tmprss2 Is Essential for Influenza H1N1 Virus Pathogenesis in Mice,http://dx.doi.org/10.1371/journal.ppat.1003774,PMC3857797,24348248,CC BY,"Annual influenza epidemics and occasional pandemics pose a severe threat to human health. Host cell factors required for viral spread but not for cellular survival are attractive targets for novel approaches to antiviral intervention. The cleavage activation of the influenza virus hemagglutinin (HA) by host cell proteases is essential for viral infectivity. However, it is unknown which proteases activate influenza viruses in mammals. Several candidates have been identified in cell culture studies, leading to the concept that influenza viruses can employ multiple enzymes to ensure their cleavage activation in the host. Here, we show that deletion of a single HA-activating protease gene, Tmprss2, in mice inhibits spread of mono-basic H1N1 influenza viruses, including the pandemic 2009 swine influenza virus. Lung pathology was strongly reduced and mutant mice were protected from weight loss, death and impairment of lung function. Also, after infection with mono-basic H3N2 influenza A virus body weight loss and survival was less severe in Tmprss2 mutant compared to wild type mice. As expected, Tmprss2-deficient mice were not protected from viral spread and pathology after infection with multi-basic H7N7 influenza A virus. In conclusion, these results identify TMPRSS2 as a host cell factor essential for viral spread and pathogenesis of mono-basic H1N1 and H3N2 influenza A viruses.",2013 Dec 5,"['Hatesuer, Bastian', 'Bertram, Stephanie', 'Mehnert, Nora', 'Bahgat, Mahmoud M.', 'Nelson, Peter S.', 'Pöhlman, Stefan', 'Schughart, Klaus']",PLoS Pathog,,,True
c0cf1c6377c3115aa80ff787332120d4ba1cd386,PMC,Coronaviruses as DNA Wannabes: A New Model for the Regulation of RNA Virus Replication Fidelity,http://dx.doi.org/10.1371/journal.ppat.1003760,PMC3857799,24348241,CC BY,,2013 Dec 5,"['Smith, Everett Clinton', 'Denison, Mark R.']",PLoS Pathog,,,True
9642cb44e010ca78890c7021b2641ad7d3fcdc69,PMC,Data Sharing in a Humanitarian Organization: The Experience of Médecins Sans Frontières,http://dx.doi.org/10.1371/journal.pmed.1001562,PMC3858219,24339750,CC BY,Unni Karunakara and colleagues discuss how Médecins Sans Frontières decided to adopt a data sharing policy for routinely collected clinical and research data in humanitarian settings and its aspirations to create a truly open data set with the first step being managed access. Please see later in the article for the Editors' Summary,2013 Dec 10,"Karunakara, Unni",PLoS Med,,,True
a9e7f41215542f62723e5118535f51d7d0c5cdab,PMC,Plasmablasts as Migratory IgG-Producing Cells in the Pathogenesis of Neuromyelitis Optica,http://dx.doi.org/10.1371/journal.pone.0083036,PMC3858367,24340077,CC BY,"Neuromyelitis optica (NMO) is an inflammatory disease characterized by recurrent attacks of optic neuritis and myelitis. It is generally accepted that autoantibodies against aquaporin 4 water channel protein play a pathogenic role in neuromyelitis optica. We have recently reported that plasmablasts are increased in the peripheral blood of this autoimmune disease, and are capable of producing autoantibodies against aquaporin 4. Here, we demonstrate that CD138(+)HLA-DR(+) plasmablasts, a subset of IgG-producing cells, are increased in the peripheral blood and are enriched among the cerebrospinal fluid (CSF) lymphocytes during the relapse of neuromyelitis optica. Notably, these CD138(+)HLA-DR(+) plasmablasts overexpress CXCR3, whose ligands are present in the cerebrospinal fluid during the relapse of neuromyelitis optica. These results led us to speculate that plasmablasts producing anti-aquaporin 4 autoantibodies might traffic toward the central nervous system (CNS). Furthermore, we performed single-cell sorting of plasmablasts from peripheral blood and CSF samples from NMO and sequenced the complementarity-determining regions (CDRs) of the IgG heavy chain expressed by the sorted plasmablast clones. There were high frequencies of mutations in the CDRs compared with framework regions, indicating that these plasmablast clones would represent a post-germinal center B-cell lineage. Consistent with the preceding results, the plasmablast clones from the peripheral blood shared the same CDR sequences with the clones from the CSF. These results indicate that IgG-producing plasmablasts, which are guided by helper T-cells, may migrate from the peripheral blood preferentially to the CSF. Since migratory plasmablasts could be involved in the inflammatory pathology of NMO, the B-cell subset and their migration might be an attractive therapeutic target.",2013 Dec 10,"['Chihara, Norio', 'Aranami, Toshimasa', 'Oki, Shinji', 'Matsuoka, Takako', 'Nakamura, Masakazu', 'Kishida, Hitaru', 'Yokoyama, Kazumasa', 'Kuroiwa, Yoshiyuki', 'Hattori, Nobutaka', 'Okamoto, Tomoko', 'Murata, Miho', 'Toda, Tatsushi', 'Miyake, Sachiko', 'Yamamura, Takashi']",PLoS One,,,True
5c10b401cc688e4f966e2ab5f41ab3a056685a3d,PMC,The Panhandle Formed by Influenza A and C Virus NS Non-Coding Regions Determines NS Segment Expression,http://dx.doi.org/10.1371/journal.pone.0081550,PMC3858493,24348921,CC BY,"Exchange of the extremities of the NS segment of type A and C influenza viruses in reverse genetics systems was used to assess their putative role in type specificity. Restoration of each specific proximal panhandle was mandatory to allow the rescue of viruses with heterotypic extremities. Moreover, the transcription level of the modified segment seemed to be directly affected by the distal panhandle strength.",2013 Nov 21,"['Crescenzo-Chaigne, Bernadette', 'Barbezange, Cyril', 'van der Werf, Sylvie']",PLoS One,,,True
e5f64cc1c75a45af66bdd08d4d480b8bd70bbe9d,PMC,iEzy-Drug: A Web Server for Identifying the Interaction between Enzymes and Drugs in Cellular Networking,http://dx.doi.org/10.1155/2013/701317,PMC3858977,24371828,CC BY,"With the features of extremely high selectivity and efficiency in catalyzing almost all the chemical reactions in cells, enzymes play vitally important roles for the life of an organism and hence have become frequent targets for drug design. An essential step in developing drugs by targeting enzymes is to identify drug-enzyme interactions in cells. It is both time-consuming and costly to do this purely by means of experimental techniques alone. Although some computational methods were developed in this regard based on the knowledge of the three-dimensional structure of enzyme, unfortunately their usage is quite limited because three-dimensional structures of many enzymes are still unknown. Here, we reported a sequence-based predictor, called “iEzy-Drug,” in which each drug compound was formulated by a molecular fingerprint with 258 feature components, each enzyme by the Chou's pseudo amino acid composition generated via incorporating sequential evolution information and physicochemical features derived from its sequence, and the prediction engine was operated by the fuzzy K-nearest neighbor algorithm. The overall success rate achieved by iEzy-Drug via rigorous cross-validations was about 91%. Moreover, to maximize the convenience for the majority of experimental scientists, a user-friendly web server was established, by which users can easily obtain their desired results.",2013 Nov 26,"['Min, Jian-Liang', 'Xiao, Xuan', 'Chou, Kuo-Chen']",Biomed Res Int,,,False
02ee87386084e0c94d20ad44138ea6488dbd293d,PMC,iEzy-Drug: A Web Server for Identifying the Interaction between Enzymes and Drugs in Cellular Networking,http://dx.doi.org/10.1155/2013/701317,PMC3858977,24371828,CC BY,"With the features of extremely high selectivity and efficiency in catalyzing almost all the chemical reactions in cells, enzymes play vitally important roles for the life of an organism and hence have become frequent targets for drug design. An essential step in developing drugs by targeting enzymes is to identify drug-enzyme interactions in cells. It is both time-consuming and costly to do this purely by means of experimental techniques alone. Although some computational methods were developed in this regard based on the knowledge of the three-dimensional structure of enzyme, unfortunately their usage is quite limited because three-dimensional structures of many enzymes are still unknown. Here, we reported a sequence-based predictor, called “iEzy-Drug,” in which each drug compound was formulated by a molecular fingerprint with 258 feature components, each enzyme by the Chou's pseudo amino acid composition generated via incorporating sequential evolution information and physicochemical features derived from its sequence, and the prediction engine was operated by the fuzzy K-nearest neighbor algorithm. The overall success rate achieved by iEzy-Drug via rigorous cross-validations was about 91%. Moreover, to maximize the convenience for the majority of experimental scientists, a user-friendly web server was established, by which users can easily obtain their desired results.",2013 Nov 26,"['Min, Jian-Liang', 'Xiao, Xuan', 'Chou, Kuo-Chen']",Biomed Res Int,,,False
4b56fb5add2d1264c928b8c0fb39d55c93a814b7,PMC,iEzy-Drug: A Web Server for Identifying the Interaction between Enzymes and Drugs in Cellular Networking,http://dx.doi.org/10.1155/2013/701317,PMC3858977,24371828,CC BY,"With the features of extremely high selectivity and efficiency in catalyzing almost all the chemical reactions in cells, enzymes play vitally important roles for the life of an organism and hence have become frequent targets for drug design. An essential step in developing drugs by targeting enzymes is to identify drug-enzyme interactions in cells. It is both time-consuming and costly to do this purely by means of experimental techniques alone. Although some computational methods were developed in this regard based on the knowledge of the three-dimensional structure of enzyme, unfortunately their usage is quite limited because three-dimensional structures of many enzymes are still unknown. Here, we reported a sequence-based predictor, called “iEzy-Drug,” in which each drug compound was formulated by a molecular fingerprint with 258 feature components, each enzyme by the Chou's pseudo amino acid composition generated via incorporating sequential evolution information and physicochemical features derived from its sequence, and the prediction engine was operated by the fuzzy K-nearest neighbor algorithm. The overall success rate achieved by iEzy-Drug via rigorous cross-validations was about 91%. Moreover, to maximize the convenience for the majority of experimental scientists, a user-friendly web server was established, by which users can easily obtain their desired results.",2013 Nov 26,"['Min, Jian-Liang', 'Xiao, Xuan', 'Chou, Kuo-Chen']",Biomed Res Int,,,False
338ea249f053b957f0681c987b83322a96a7350b,PMC,iEzy-Drug: A Web Server for Identifying the Interaction between Enzymes and Drugs in Cellular Networking,http://dx.doi.org/10.1155/2013/701317,PMC3858977,24371828,CC BY,"With the features of extremely high selectivity and efficiency in catalyzing almost all the chemical reactions in cells, enzymes play vitally important roles for the life of an organism and hence have become frequent targets for drug design. An essential step in developing drugs by targeting enzymes is to identify drug-enzyme interactions in cells. It is both time-consuming and costly to do this purely by means of experimental techniques alone. Although some computational methods were developed in this regard based on the knowledge of the three-dimensional structure of enzyme, unfortunately their usage is quite limited because three-dimensional structures of many enzymes are still unknown. Here, we reported a sequence-based predictor, called “iEzy-Drug,” in which each drug compound was formulated by a molecular fingerprint with 258 feature components, each enzyme by the Chou's pseudo amino acid composition generated via incorporating sequential evolution information and physicochemical features derived from its sequence, and the prediction engine was operated by the fuzzy K-nearest neighbor algorithm. The overall success rate achieved by iEzy-Drug via rigorous cross-validations was about 91%. Moreover, to maximize the convenience for the majority of experimental scientists, a user-friendly web server was established, by which users can easily obtain their desired results.",2013 Nov 26,"['Min, Jian-Liang', 'Xiao, Xuan', 'Chou, Kuo-Chen']",Biomed Res Int,,,True
c4e99c8b861f4457b4a0518860bc9e52f5348e87,PMC,Zoos through the Lens of the IUCN Red List: A Global Metapopulation Approach to Support Conservation Breeding Programs,http://dx.doi.org/10.1371/journal.pone.0080311,PMC3859473,24348999,CC BY,"Given current extinction trends, the number of species requiring conservation breeding programs (CBPs) is likely to increase dramatically. To inform CBP policies for threatened terrestrial vertebrates, we evaluated the number and representation of threatened vertebrate species on the IUCN Red List held in the ISIS zoo network and estimated the complexity of their management as metapopulations. Our results show that 695 of the 3,955 (23%) terrestrial vertebrate species in ISIS zoos are threatened. Only two of the 59 taxonomic orders show a higher proportion of threatened species in ISIS zoos than would be expected if species were selected at random. In addition, for most taxa, the management of a zoo metapopulation of more than 250 individuals will require the coordination of a cluster of 11 to 24 ISIS zoos within a radius of 2,000 km. Thus, in the zoo network, the representation of species that may require CBPs is currently low and the spatial distribution of these zoo populations makes management difficult. Although the zoo community may have the will and the logistical potential to contribute to conservation actions, including CBPs, to do so will require greater collaboration between zoos and other institutions, alongside the development of international agreements that facilitate cross-border movement of zoo animals. To maximize the effectiveness of integrated conservation actions that include CBPs, it is fundamental that the non-zoo conservation community acknowledges and integrates the expertise and facilities of zoos where it can be helpful.",2013 Dec 11,"['Conde, Dalia A.', 'Colchero, Fernando', 'Gusset, Markus', 'Pearce-Kelly, Paul', 'Byers, Onnie', 'Flesness, Nate', 'Browne, Robert K.', 'Jones, Owen R.']",PLoS One,,,True
cf7837069ab6a12d5663c6f3c715b73fe53493a1,PMC,Cellular microRNA miR-181b Inhibits Replication of Mink Enteritis Virus by Repression of Non-Structural Protein 1 Translation,http://dx.doi.org/10.1371/journal.pone.0081515,PMC3859502,24349084,CC BY,"Mink enteritis virus (MEV) is one of the most important viral pathogens in the mink industry. Recent studies have showed that microRNAs (miRNAs), small noncoding RNAs of length ranging from 18–23 nucleotides (nt) participate in host-pathogen interaction networks; however, whether or not miRNAs are involved in MEV infection has not been reported. Our study revealed that miRNA miR-181b inhibited replication of MEV in the feline kidney (F81) cell line by targeting the MEV non-structural protein 1 (NS1) messenger RNA (mRNA) coding region, resulting in NS1 translational repression, while MEV infection reduced miR-181b expression. This is the first description of cellular miRNAs modulating MEV infection in F81 cells, providing further insight into the mechanisms of viral infection, and may be useful in development of naturally-occurring miRNAs antiviral strategies.",2013 Dec 11,"['Sun, Jia-zeng', 'Wang, Jigui', 'Yuan, Daoli', 'Wang, Shuang', 'Li, Zhili', 'Yi, Bao', 'Mao, Yaping', 'Hou, Qiang', 'Liu, Weiquan']",PLoS One,,,True
3c440b07b2bc59e8483537e994bbd7ac0030801a,PMC,A Leaderless Genome Identified during Persistent Bovine Coronavirus Infection Is Associated with Attenuation of Gene Expression,http://dx.doi.org/10.1371/journal.pone.0082176,PMC3861326,24349214,CC BY,"The establishment of persistent viral infection is often associated with the selection of one or more mutant viruses. For example, it has been found that an intraleader open reading frame (ORF) in genomic and subgenomic mRNA (sgmRNA) molecules is selected during bovine coronavirus (BCoV) persistence which leads to translation attenuation of the downstream ORF. Here, we report the unexpected identification of leaderless genomes, in addition to leader-containing genomes, in a cell culture persistently infected with BCoV. The discovery was made by using a head-to-tail ligation method that examines genomic 5′-terminal sequences at different times postinfection. Functional analyses of the leaderless genomic RNA in a BCoV defective interfering (DI) RNA revealed that (1) the leaderless genome was able to serve as a template for the synthesis of negative-strand genome, although it cannot perform replicative positive-strand genomic RNA synthesis, and (2) the leaderless genome retained its function in translation and transcription, although the efficiency of these processes was impaired. Therefore, this previously unidentified leaderless genome is associated with the attenuation of genome expression. Whether the leaderless genome contributes to the establishment of persistent infection remains to be determined.",2013 Dec 12,"['Ke, Ting-Yung', 'Liao, Wei-Yu', 'Wu, Hung-Yi']",PLoS One,,,True
4ee2232fd9b2088955ad781243f135dc76edbaf1,PMC,Endoplasmic Reticulum Stress Contributes to Helicobacter Pylori VacA-Induced Apoptosis,http://dx.doi.org/10.1371/journal.pone.0082322,PMC3862672,24349255,CC0,"Vacuolating cytotoxin A (VacA) is one of the important virulence factors produced by H. pylori. VacA induces apoptotic cell death, which is potentiated by ammonia. VacA also causes cell death by mitochondrial damage, via signaling pathways that are not fully defined. Our aim was to determine whether endoplasmic reticulum (ER) stress is associated with VacA-induced mitochondrial dysfunction and apoptosis. We found that C/EBP homologous protein (CHOP), a key signaling protein of ER stress-induced apoptosis, was transcriptionally up-regulated following incubation of gastric epithelial cells with VacA. The effect of VacA on CHOP induction was significantly enhanced by co-incubation with ammonium chloride. Phosphorylation of eukaryotic initiation factor 2 (eIF2)-alpha, which is known to occur downstream of the ER stress sensor PKR-like ER-localized eIF2-alpha kinase (PERK) and to regulate CHOP expression, was also observed following incubation with VacA in the presence of ammonium chloride. Knockdown of CHOP by siRNA resulted in inhibition of VacA-induced apoptosis. Further studies showed that silencing of the PERK gene with siRNA attenuated VacA-mediated phosphorylation of eIF2-alpha, CHOP induction, expression of BH3-only protein Bim and Bax activation, and cell death induced by VacA with ammonium chloride, indicating that ER stress may lead to mitochondrial dysfunction during VacA-induced toxicity. Activation of ER stress and up-regulation of BH3-only proteins were also observed in human H. pylori-infected gastric mucosa. Collectively, this study reveals a possible association between VacA-induced apoptosis in gastric epithelial cells, and activation of ER stress in H. pylori-positive gastric mucosa.",2013 Dec 13,"['Akazawa, Yuko', 'Isomoto, Hajime', 'Matsushima, Kayoko', 'Kanda, Tsutomu', 'Minami, Hitomi', 'Yamaghchi, Naoyuki', 'Taura, Naota', 'Shiozawa, Ken', 'Ohnita, Ken', 'Takeshima, Fuminao', 'Nakano, Masayuki', 'Moss, Joel', 'Hirayama, Toshiya', 'Nakao, Kazuhiko']",PLoS One,,,True
5d46c99fa67d9b839724a7349e6ffb22ba71cf1d,PMC,"Surveillance, response systems, and evidence updates on emerging zoonoses: the role of one health",http://dx.doi.org/10.3402/iee.v3i0.21386,PMC3864162,24363836,CC BY,"Globally, emerging zoonotic diseases are increasing. Existing surveillance systems for zoonoses have substantial gaps, especially in developing countries, and the systems in place in the developed world require improvements. Resources and updates on evidence-based practice (EBP) for zoonoses are sparser in the veterinary literature as compared to the medical literature. Evidence updates for emerging zoonoses are either absent or rudimentary in both human and veterinary medicine. A ‘one-health’ concept, including a global signaling surveillance system for emerging zoonoses, will be essential for correct diagnoses, interventions, and public health strategies. An open access EBP platform supported by builders of EBP resources is urgently needed to counter emerging zoonoses.",2013 Dec 13,"['Asokan, G. V.', 'Kasimanickam, Ramanathan K.', 'Asokan, Vanitha']",Infect Ecol Epidemiol,,,True
046a56d635edc933ed8f30ccf1ae9fd488dfe645,PMC,Tat Peptide-Mediated Soluble Expression of the Membrane Protein LSECtin-CRD in Escherichia coli,http://dx.doi.org/10.1371/journal.pone.0083579,PMC3865297,24358298,CC BY,"The human liver and lymph node sinusoidal endothelial cell C-type lectin (hLSECtin), a type II integral membrane protein, containing a Ca(2+)-dependent carbohydrate recognition domain (CRD), has a well-established biological activity, yet its three-dimensional structure is unknown due to low expression yields and aggregation into inclusion bodies. Previous study has demonstrated that the HIV-1 virus-encoded Tat peptide (‘YGRKKRRQRRR’) can increase the yields and the solubility of heterologous proteins. However, whether the Tat peptide could promote the high-yield and soluble expression of membrane proteins in Escherichia coli is not known. Therefore, the prokaryotic expression vector pET28b-Tat-hLSECtin-CRD (using pET28b and pET28b-hLSECtin-CRD as controls) was constructed, and transformed into E. coli BL21 (DE3) cells and induced with isopropyl-β-d-thiogalactoside (IPTG) followed with identifying by SDS-PAGE and Western blot. Subsequently, the bacterial subcellular structure, in which overexpressed the heterologous proteins Tat-hLSECtin-CRD and Tat-free hLSECtin-CRD, was analyzed by transmission electron microscope (TEM) respectively, and the mannose-binding activity of Tat-hLSECtin-CRD was also determined. Expectedly, the solubility of Tat-LSECtin-CRD significantly increased compared to Tat-free LSECtin-CRD (**p < 0.01) with prolonged time, and the Tat-LSECtin-CRD had a significant mannose-binding activity. The subcellular structure analysis indicated that the bacterial cells overexpressed Tat-hLSECtin-CRD exhibited denser region compared with controls, while dot denser region aggregated in the two ends of bacterial cells overexpressed Tat-free hLSECtin-CRD. This study provided a novel method for improving the soluble expression of membrane proteins in prokaryotic systems by fusion with the Tat peptide, which may be potentially expanded to the expression of other membrane proteins.",2013 Dec 16,"['Dong, Guofu', 'Wang, Changzhen', 'Wu, Yonghong', 'Cong, Jianbo', 'Cheng, Li', 'Wang, Mingqun', 'Zhao, Pengkai', 'Tang, Li', 'Zhang, Chenggang', 'Wu, Ke']",PLoS One,,,True
83f5dbddb15c7cc6ad9d27d00ba1226462845440,PMC,Antisense suppression of donor splice site mutations in the dystrophin gene transcript,http://dx.doi.org/10.1002/mgg3.19,PMC3865583,24498612,CC BY,"We describe two donor splice site mutations, affecting dystrophin exons 16 and 45 that led to Duchenne muscular dystrophy (DMD), through catastrophic inactivation of the mRNA. These gene lesions unexpectedly resulted in the retention of the downstream introns, thereby increasing the length of the dystrophin mRNA by 20.2 and 36 kb, respectively. Splice-switching antisense oligomers targeted to exon 16 excised this in-frame exon and the following intron from the patient dystrophin transcript very efficiently in vitro, thereby restoring the reading frame and allowing synthesis of near-normal levels of a putatively functional dystrophin isoform. In contrast, targeting splice-switching oligomers to exon 45 in patient cells promoted only modest levels of an out-of-frame dystrophin transcript after transfection at high oligomer concentrations, whereas dual targeting of exons 44 and 45 or 45 and 46 resulted in more efficient exon skipping, with concomitant removal of intron 45. The splice site mutations reported here appear highly amenable to antisense oligomer intervention. We suggest that other splice site mutations may need to be evaluated for oligomer interventions on a case-by-case basis.",2013 Sep 13,"['Fletcher, Sue', 'Meloni, Penny L', 'Johnsen, Russell D', 'Wong, Brenda L', 'Muntoni, Francesco', 'Wilton, Stephen D']",Mol Genet Genomic Med,,,True
4300be597ccbea9acb374312063e2776b7f631c4,PMC,"Epidemiology of Human Respiratory Viruses in Children with Acute Respiratory Tract Infections in Jinan, China",http://dx.doi.org/10.1155/2013/210490,PMC3865640,24363757,CC BY,"The viral etiologies of UTRIs and LTRIs in children in Jinan city were investigated between July 2009 and June 2010. Nasal and throat swabs were collected from 397 children with URTIs and bronchoalveolar lavage fluid specimens were collected from 323 children with LRTIs. RT-PCR/PCR was used to examine all samples for IFV, PIV, RSV, RV, hMPV, HBoV, CoV, ADV, RSV, and EV. Viral pathogens were detected in 47.10% of URTI samples and 66.57% samples, and the incidence of viral coinfection was 5.29% and 21.05%, respectively. IFV was the most common virus in URTIs, with a detection rate of 19.40%, followed by PIV (10.83%), RV (10.58%), and EV (6.30%). For LRTIs, PIV and RV were both detected in 27% of samples, followed by RSV (9.91%), HBoV (8.36%), IFV (5.57%), and hMPV (5.57%). RSV and HBoV were more prevalent in the youngest children of no more than six months. Meanwhile, RV, PIV, and RSV were the most frequent viruses combined with bacterial pathogens in LRTIs. In conclusion, the spectrum of respiratory virus infections in URTIs and LRTIs differed in terms of the most common pathogens, seasonal distribution, and coinfection rate.",2013 Dec 2,"['Lu, Yanqin', 'Wang, Shifu', 'Zhang, Lehai', 'Xu, Chao', 'Bian, Cuirong', 'Wang, Zhaoxia', 'Ma, Yanhui', 'Wang, Ke', 'Ma, Lixia', 'Meng, Chen', 'Ni, Caiyun', 'Tong, Jiabei', 'Li, Gongchao', 'Han, Jinxiang']",Clin Dev Immunol,,,True
88249503fb8dd13282a60ceac441edd59e1c5be3,PMC,Glucocorticosteroid in Treatment of Severe Pneumonia,http://dx.doi.org/10.1155/2013/865635,PMC3865735,24363503,CC BY,"Airway diseases such as pneumonia constitute a major health burden on a global scale; untreated pneumonia may develop to severe pneumonia and consequently lead to to fatal episodes of mortality and morbidity. The balance between inflammatory mediators is key for the outcome of the pulmonary infection; elimination of invading pathogen was marked by the release of cytokines and other inflammatory mediators from alveolar macrophages and glucocorticoid steroids (GCs) acting on the inflammatory component. Treatments of severe pneumonia with GCs have been developing for years with inconclusive results. In many cases GCs have been administered empirically without clinical evidence. Recent studies assess beneficial impact on treatment of severe pneumonia by suggesting specific dosage, period of administration, and tapered dosage.",2013 Dec 2,"['Ariani, Felinda', 'Liu, Kaixiong', 'Jing, Zhang', 'Qu, Jieming']",Mediators Inflamm,,,True
c9bcd70bf18a413b1af105124cc232f2fe0fd5b9,PMC,A Replicating Modified Vaccinia Tiantan Strain Expressing an Avian-Derived Influenza H5N1 Hemagglutinin Induce Broadly Neutralizing Antibodies and Cross-Clade Protective Immunity in Mice,http://dx.doi.org/10.1371/journal.pone.0083274,PMC3866202,24358269,CC BY,"To combat the possibility of a zoonotic H5N1 pandemic in a timely fashion, it is necessary to develop a vaccine that would confer protection against homologous and heterologous human H5N1 influenza viruses. Using a replicating modified vaccinia virus Tian Tan strain (MVTT) as a vaccine vector, we constructed MVTT(HA-QH) and MVTT(HA-AH), which expresses the H5 gene of a goose-derived Qinghai strain A/Bar-headed Goose/Qinghai/1/2005 or human-derived Anhui Strain A/Anhui/1/2005. The immunogenicity profiles of both vaccine candidates were evaluated. Vaccination with MVTT(HA-QH) induced a significant level of neutralizing antibodies (Nabs) against a homologous strain and a wide range of H5N1 pseudoviruses (clades 1, 2.1, 2.2, 2.3.2, and 2.3.4). Neutralization tests (NT) and Haemagglutination inhibition (HI) antibodies inhibit the live autologous virus as well as a homologous A/Xingjiang/1/2006 and a heterologous A/Vietnam/1194/2004, representing two human isolates from clade 2.2 and clade 1, respectively. Importantly, mice vaccinated with intranasal MVTT(HA-QH) were completely protected from challenge with lethal dosages of A/Bar-headed Goose/Qinghai/1/2005 and the A/Viet Nam/1194/2004, respectively, but not control mice that received a mock MVTT(S) vaccine. However, MVTT(HA-AH) induced much lower levels of NT against its autologous strain. Our results suggest that it is feasible to use the H5 gene from A/Bar-headed Goose/Qinghai/1/2005 to construct an effective vaccine, when using MVTT as a vector, to prevent infections against homologous and genetically divergent human H5N1 influenza viruses.",2013 Dec 17,"['Xiao, Haixia', 'Liu, Li', 'Zhu, Qingyu', 'Tan, Zhiwu', 'Yu, Wenbo', 'Tang, Xian', 'Zhan, Dawei', 'Du, Yanhua', 'Wang, Haibo', 'Liu, Di', 'Li, Zhixin', 'Yuen, Kwok-Yung', 'Ho, David D.', 'Gao, George F.', 'Chen, Zhiwei']",PLoS One,,,True
e9b3af3ad2b2abfacc4228e0ae590cc645f29718,PMC,Application of an Amine Functionalized Biopolymer in the Colonic Delivery of Glycyrrhizin: A Design and In Vivo Efficacy Study,http://dx.doi.org/10.3797/scipharm.1301-14,PMC3867243,24482776,CC BY,"In our current study, a newer amine functionalized guar gum derivative was studied for its efficacy in colonic drug delivery. Glycyrrhizic acid mono-ammonium salt was used as the model drug. Drug-loaded microparticles were formulated by ionic crosslinking using sodium tripolyphosphate. The Scanning Electron Microscopic study revealed spherical particles of sizes from 4.9 ± 3.8 μm to 6.9 ± 3.9 μm. The FT-IR studies presented a possible interaction between the drug and the polymer. The drug was encapsulated in amorphous form as observed from the powder X-Ray Diffraction studies. A cumulative drug release study was carried out in simulated gastric, intestinal, and colonic fluids. The cumulative drug release studies presented a burst release followed by a sustained release of the drug in simulated colonic fluid containing rat cecal contents. The drug-polymer ratio was optimised using a 3(2) factorial design by taking the amounts of glycyrrhizic acid (X(1)) and guar gum alkyl amine (X(2)) as the independant variables. The percent cumulative drug release at 240 mins (Q(240)), 720 mins (Q(720)), and at 1,440 mins (Q(1440)) were considered as the dependant variables. The efficacy of the optimized formulation was studied in a 2,4,6-trinitrobenzene sulfonic acid-induced rat colitis model. The tissue’s nitric oxide, malondialdehyde, and myeloperoxidase activities were found to be much lower in the microparticle-treated group compared to free drug-treated group. The histology of the colonic tissue from the treated group of animals revealed almost no infiltration of inflammatory cells in the tissue for the microparticle-treated group of animals. The synthesized amine derivative of guar gum was found to be better in vitro with a better in vivo efficacy in the colonic delivery of glycyrrhizic acid monoammonium salt and can be considered as a newer modified biopolymer for colonic drug delivery.",2013 May 18 Oct-Dec,"['Kumar De, Amit', 'Datta, Sriparna', 'Mukherjee, Arup']",Sci Pharm,,,True
5159ab148faaafed700258c0a6278cb1fb5476e7,PMC,"Characterization of the Complete Genome of Chikungunya in Zhejiang, China, Using a Modified Virus Discovery Method Based on cDNA-AFLP",http://dx.doi.org/10.1371/journal.pone.0083014,PMC3867435,24367579,CC BY,"BACKGROUND: Chikungunya (CHIK) virus is a mosquito-borne emerging pathogen presenting great health challenges worldwide, particularly in tropical zones. Here we report a newly detected strain of CHIK, Zhejiang/chik-sy/2012, in China, a nonindigenous region for CHIK, using a modified approach based on the classic cDNA-AFLP. We then performed etiological and phylogenetic analyses to better understand its molecular characterization and phylogenetic pattern, and also to aid in further evaluating its persistence in Southeast Asia. METHODS: By using this modified procedure, we determined for the first time the complete genome sequence of the chikungunya virus strain, Zhejiang/chik-sy/2012, isolated in 2012 from a patient in Zhejiang, China. Sequence analyses revealed that this positive single strand of RNA is 12,017 bp long. We found no single amino acid mutation in A226V, D284E and A316V. Phylogenetic analysis showed that our strain shared the greatest homology with a strain isolated in Taiwan, which was derived from a strain from Indonesia. Chik-sy/2012 is in a different clade from other CHIK viruses found in China previously. CONCLUSIONS: A modified cDNA-AFLP in virus discovery was used to isolate the first CHIK and the first complete genome sequence of virus strain chik-sy/2012 in 2012 from a patient with CHIK fever in Zhejiang, China. The infection displayed great phylogenetic distance from viruses detected in Guangdong, China, in 2008 and 2010, since they were derived from another evolutionary lineage. Additional molecular epidemiology data are needed to further understand, monitor and evaluate CHIK in China.",2013 Dec 18,"['Sun, Yi', 'Yan, JuYing', 'Mao, HaiYan', 'Zhang, Lei', 'Lyu, QinFeng', 'Wu, ZhongHua', 'Zheng, Wei', 'Feng, Cen', 'Zhang, YanJun']",PLoS One,,,True
d6f350fa81730f8476614ffe7280454633d77f31,PMC,"The Cytokine and Chemokine Profiles in Patients with Hand, Foot and Mouth Disease of Different Severities in Shanghai, China, 2010",http://dx.doi.org/10.1371/journal.pntd.0002599,PMC3868519,24367714,CC BY,"BACKGROUND AND PURPOSE: Systemic upregulation of inflammatory cytokines is characteristic of critical severe hand, foot, and mouth disease (HFMD) with pulmonary edema. Thus, immunomodulatory medicines such as steroids, including methylprednisolone, have been proposed to treat patients with severe HFMD in China, because it is postulated that inflammatory cytokines play a role in the development of severe complications. This study is to further investigate the inflammatory response in the relatively mild HFMD patients, and whether steroid treatment has a beneficial effect on the suppression of inflammation in HFMD patients. METHOD: We measured the levels of 50 kinds of chemokines, cytokines, growth factors and soluble receptors in serum samples from control patients without HFMD and the HFMD patients with or without prior treatment of intravenous methylprednisolone. RESULTS: Our present study found that even relatively mild HFMD patients without central nervous system (CNS) complications had elevated serum levels of inflammatory cytokines, including interleukin (IL)-3, IL-6, IL-12p40, and tumor necrosis factor (TNF)-α, which suggested systemic inflammation. In contrast, these patients also have decreased levels of other serum biomarkers, including IL-1Ra, IL-8, IL-16, soluble ICAM-1, CXCL-1, and CCL27. The dysregulation of cytokine and chemokine expression may be involved in CNS complications and unbalanced circulating leukocytes in HFMD patients. Surprisingly, patients treated with methylprednisolone had no difference in the expression levels of HFMD-associated biomarkers instead had slightly increased levels of IL-17A, which was not associated with the occurrence of HFMD. CONCLUSION: Whether steroid treatment has any beneficial effect on the prognosis of HFMD patients requires to be further investigated.",2013 Dec 19,"['Zeng, Mei', 'Zheng, Xiaoyan', 'Wei, Ruicheng', 'Zhang, Na', 'Zhu, Kai', 'Xu, Bin', 'Yang, Chun-Hui', 'Yang, Chun-Fu', 'Deng, Chaoyang', 'Pu, Dongbo', 'Wang, Xiaohong', 'Altmeyer, Ralf', 'Leng, Qibin']",PLoS Negl Trop Dis,,,True
2be4d8ed799f2556c53e6946720e3033d41060e2,PMC,"Space-Time Clustering Characteristics of Tuberculosis in China, 2005-2011",http://dx.doi.org/10.1371/journal.pone.0083605,PMC3868653,24367604,CC BY,"OBJECTIVES: China is one of the 22 tuberculosis (TB) high-burden countries in the world. As TB is a major public health problem in China, spatial analysis could be applied to detect geographic distribution of TB clusters for targeted intervention on TB epidemics. METHODS: Spatial analysis was applied for detecting TB clusters on county-based TB notification data in the national notifiable infectious disease case reporting surveillance system from 2005 to 2011. Two indicators of TB epidemic were used including new sputum smear-positive (SS+) notification rate and total TB notification rate. Global Moran’s I by ArcGIS was used to assess whether TB clustering and its trend were significant. SaTScan software that used the retrospective space-time analysis and Possion probability model was utilized to identify geographic areas and time period of potential clusters with notification rates on county-level from 2005 to 2011. RESULTS: Two indicators of TB notification had presented significant spatial autocorrelation globally each year (p<0.01). Global Moran’s I of total TB notification rate had positive trend as time went by (t=6.87, p<0.01). The most likely clusters of two indicators had similar spatial distribution and size in the south-central regions of China from 2006 to 2008, and the secondary clusters in two regions: northeastern China and western China. Besides, the secondary clusters of total TB notification rate had two more large clustering centers in Inner Mongolia, Gansu and Qinghai provinces and several smaller clusters in Shanxi, Henan, Hebei and Jiangsu provinces. CONCLUSION: The total TB notification cases clustered significantly in some special areas each year and the clusters trended to aggregate with time. The most-likely and secondary clusters that overlapped among two TB indicators had higher TB burden and risks of TB transmission. These were the focused geographic areas where TB control efforts should be prioritized.",2013 Dec 19,"['Zhao, Fei', 'Cheng, Shiming', 'He, Guangxue', 'Huang, Fei', 'Zhang, Hui', 'Xu, Biao', 'Murimwa, Tonderayi C.', 'Cheng, Jun', 'Hu, Dongmei', 'Wang, Lixia']",PLoS One,,,True
81d0bac38646d309a178010b68ebf0e11d43101c,PMC,NEWS,http://dx.doi.org/10.7189/jogh.03.020202,PMC3868822,,CC BY,,2013 Dec,,J Glob Health,,,False
35d8d53b4907862f8ad0c6f72e6905204d4c9562,PMC,Full-Length Genome Sequence of a Plaque-Cloned Virulent Porcine Epidemic Diarrhea Virus Isolate (USA/Iowa/18984/2013) from a Midwestern U.S. Swine Herd,http://dx.doi.org/10.1128/genomeA.01049-13,PMC3868854,24356830,CC BY,Porcine epidemic diarrhea (PED) was recognized in U.S. swine for the first time in early 2013. A plaque-purified PED virus (PEDV) isolate (USA/Iowa/18984/2013) was obtained from a diarrheic piglet. The isolate is genetically close to other previously reported U.S. PEDVs and recent Chinese PEDVs and was virulent when inoculated into neonatal pigs.,2013 Dec 19,"['Hoang, Hai', 'Killian, Mary L.', 'Madson, Darin M.', 'Arruda, Paulo H. E.', 'Sun, Dong', 'Schwartz, Kent J.', 'Yoon, Kyoungjin J.']",Genome Announc,,,True
b94abc8c5e511d49e02cc4175cccc27629f5ee76,PMC,Transcriptome analysis of chicken kidney tissues following coronavirus avian infectious bronchitis virus infection,http://dx.doi.org/10.1186/1471-2164-14-743,PMC3870970,24168272,CC BY,"BACKGROUND: Infectious bronchitis virus (IBV), a prototype of the Coronaviridae family, is an economically important causative agent of infectious bronchitis in chickens and causes an acute and highly contagious upper respiratory tract infections that may lead to nephritis. However, the molecular antiviral mechanisms of chickens to IBV infection remain poorly understood. In this study, we conducted global gene expression profiling of chicken kidney tissue after nephropathogenic IBV infection to better understand the interactions between host and virus. RESULTS: IBV infection contributed to differential expression of 1777 genes, of which 876 were up-regulated and 901 down-regulated in the kidney compared to those of control chickens and 103 associated with immune and inflammatory responses may play important roles in the host defense response during IBV infection. Twelve of the altered immune-related genes were confirmed by real-time RT-PCR. Gene ontology category, KEGG pathway, and gene interaction networks (STRING analysis) were analyzed to identify relationships among differentially expressed genes involved in signal transduction, cell adhesion, immune responses, apoptosis regulation, positive regulation of the I-kappaB kinase/NF-kappaB cascade and response to cytokine stimulus. Most of these genes were related and formed a large network, in which IL6, STAT1, MYD88, IRF1 and NFKB2 were key genes. CONCLUSIONS: Our results provided comprehensive knowledge regarding the host transcriptional response to IBV infection in chicken kidney tissues, thereby providing insight into IBV pathogenesis, particularly the involvement of innate immune pathway genes associated with IBV infection.",2013 Oct 30,"['Cong, Feng', 'Liu, Xiaoli', 'Han, Zongxi', 'Shao, Yuhao', 'Kong, Xiangang', 'Liu, Shengwang']",BMC Genomics,,,True
11227aa67f131d1b8220d5c45b4bf592f0a48ef4,PMC,The discovery and identification of a candidate proteomic biomarker of active tuberculosis,http://dx.doi.org/10.1186/1471-2334-13-506,PMC3870977,24168695,CC BY,"BACKGROUND: Noninvasive and convenient biomarkers for early diagnosis of tuberculosis (TB) remain an urgent need. The aim of this study was to discover and identify potential biomarkers specific for TB. METHODS: The surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from 180 cases of TB and 211 control subjects. A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by reverse phase-high performance liquid chromatography (RP-HPLC), identified by MALDI-TOF MS, LC-MS/MS and validated using enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 35 discriminating m/z peaks were detected that were related to TB (P < 0.01). The model of biomarkers based on the four biomarkers (2554.6, 4824.4, 5325.7, and 8606.8 Da) was established which could distinguish TB from controls with the sensitivity of 83.3% and the specificity of 84.2%. The candidate biomarker with m/z of 2554.6 Da was found to be up-regulated in TB patients, and was identified as a fragment of fibrinogen, alpha polypeptide isoform alpha-E preproprotein. Analysis in 22 patients with TB showed increased fibrinogen degradation product (FDP) (5,005 ± 1,297 vs. 4,010 ± 1,181 ng/mL, P < 0.05) and in 142 patients showed elevated plasma fibrinogen levels. CONCLUSIONS: A diagnostic model for TB with high sensitivity and specificity was developed using mass spectrometry combined with magnetic beads. Fibrinogen was identified as a potential biomarker for TB and showed diagnostic values in clinical application.",2013 Oct 29,"['Liu, Jiyan', 'Jiang, Tingting', 'Wei, Liliang', 'Yang, Xiuyun', 'Wang, Chong', 'Zhang, Xing', 'Xu, Dandan', 'Chen, Zhongliang', 'Yang, Fuquan', 'Li, Ji-Cheng']",BMC Infect Dis,,,True
9f824ee0252ae66915b8dc9b593366f921b6d615,PMC,The discovery and identification of a candidate proteomic biomarker of active tuberculosis,http://dx.doi.org/10.1186/1471-2334-13-506,PMC3870977,24168695,CC BY,"BACKGROUND: Noninvasive and convenient biomarkers for early diagnosis of tuberculosis (TB) remain an urgent need. The aim of this study was to discover and identify potential biomarkers specific for TB. METHODS: The surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from 180 cases of TB and 211 control subjects. A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by reverse phase-high performance liquid chromatography (RP-HPLC), identified by MALDI-TOF MS, LC-MS/MS and validated using enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 35 discriminating m/z peaks were detected that were related to TB (P < 0.01). The model of biomarkers based on the four biomarkers (2554.6, 4824.4, 5325.7, and 8606.8 Da) was established which could distinguish TB from controls with the sensitivity of 83.3% and the specificity of 84.2%. The candidate biomarker with m/z of 2554.6 Da was found to be up-regulated in TB patients, and was identified as a fragment of fibrinogen, alpha polypeptide isoform alpha-E preproprotein. Analysis in 22 patients with TB showed increased fibrinogen degradation product (FDP) (5,005 ± 1,297 vs. 4,010 ± 1,181 ng/mL, P < 0.05) and in 142 patients showed elevated plasma fibrinogen levels. CONCLUSIONS: A diagnostic model for TB with high sensitivity and specificity was developed using mass spectrometry combined with magnetic beads. Fibrinogen was identified as a potential biomarker for TB and showed diagnostic values in clinical application.",2013 Oct 29,"['Liu, Jiyan', 'Jiang, Tingting', 'Wei, Liliang', 'Yang, Xiuyun', 'Wang, Chong', 'Zhang, Xing', 'Xu, Dandan', 'Chen, Zhongliang', 'Yang, Fuquan', 'Li, Ji-Cheng']",BMC Infect Dis,,,False
871bb1d475d0dbb910cce25e16d066adf9706a4c,PMC,"Functional Limitations of Plasmacytoid Dendritic Cells Limit Type I Interferon, T Cell Responses and Virus Control in Early Life",http://dx.doi.org/10.1371/journal.pone.0085302,PMC3871569,24376875,CC BY,"Infant mortality from viral infection remains a major global health concern: viruses causing acute infections in immunologically mature hosts often follow a more severe course in early life, with prolonged or persistent viral replication. Similarly, the WE strain of lymphocytic choriomeningitis virus (LCMV-WE) causes acute self-limiting infection in adult mice but follows a protracted course in infant animals, in which LCMV-specific CD8(+) T cells fail to expand and control infection. By disrupting type I IFNs signaling in adult mice or providing IFN-α supplementation to infant mice, we show here that the impaired early life T cell responses and viral control result from limited early type I IFN responses. We postulated that plasmacytoid dendritic cells (pDC), which have been identified as one major source of immediate-early IFN-I, may not exert adult-like function in vivo in the early life microenvironment. We tested this hypothesis by studying pDC functions in vivo during LCMV infection and identified a coordinated downregulation of infant pDC maturation, activation and function: despite an adult-like in vitro activation capacity of infant pDCs, the expression of the E2-2 pDC master regulator (and of critical downstream antiviral genes such as MyD88, TLR7/TLR9, NF-κB, IRF7 and IRF8) is downregulated in vivo at baseline and during LCMV infection. A similar pattern was observed in response to ssRNA polyU, a model ligand of the TLR7 viral sensor. This suggests that the limited T cell-mediated defense against early life viral infections is largely attributable to / regulated by infant pDC responses and provides incentives for novel strategies to supplement or stimulate immediate-early IFN-α responses.",2013 Dec 23,"['Belnoue, Elodie', 'Fontannaz, Paola', 'Rochat, Anne-Françoise', 'Tougne, Chantal', 'Bergthaler, Andreas', 'Lambert, Paul-Henri', 'Pinschewer, Daniel D.', 'Siegrist, Claire-Anne']",PLoS One,,,True
8762daff0f7890b72f611247c1a15133ea291afb,PMC,"Recent Advances in Diagnosis, Prevention, and Treatment of Human Respiratory Syncytial Virus",http://dx.doi.org/10.1155/2013/595768,PMC3872095,24382964,CC BY,"Human respiratory syncytial virus (RSV) is a common cause of respiratory infection in infants and the elderly, leading to significant morbidity and mortality. The interdisciplinary fields, especially biotechnology and nanotechnology, have facilitated the development of modern detection systems for RSV. Many anti-RSV compounds like fusion inhibitors and RNAi molecules have been successful in laboratory and clinical trials. But, currently, there are no effective drugs for RSV infection even after decades of research. Effective diagnosis can result in effective treatment, but the progress in both of these facets must be concurrent. The development in prevention and treatment measures for RSV is at appreciable pace, but the implementation into clinical practice still seems a challenge. This review attempts to present the promising diverse research approaches and advancements in the area of diagnosis, prevention, and treatment that contribute to RSV management.",2013 Dec 9,"['Bawage, Swapnil Subhash', 'Tiwari, Pooja Munnilal', 'Pillai, Shreekumar', 'Dennis, Vida', 'Singh, Shree Ram']",Adv Virol,,,True
575aa2758f4a3c952d7cd9ab031eb42b25a87a96,PMC,Sensing Microbial RNA in the Cytosol,http://dx.doi.org/10.3389/fimmu.2013.00468,PMC3872322,24400006,CC BY,"The innate immune system faces the difficult task of keeping a fine balance between sensitive detection of microbial presence and avoidance of autoimmunity. To this aim, key mechanisms of innate responses rely on isolation of pathogens in specialized subcellular compartments, or sensing of specific microbial patterns absent from the host. Efficient detection of foreign RNA in the cytosol requires an additional layer of complexity from the immune system. In this particular case, innate sensors should be able to distinguish self and non-self molecules that share several similar properties. In this review, we discuss this interplay between cytosolic pattern recognition receptors and the microbial RNA they detect. We describe how microbial RNAs gain access to the cytosol, which receptors they activate and counter-strategies developed by microorganisms to avoid this response.",2013 Dec 25,"['Vabret, Nicolas', 'Blander, J. Magarian']",Front Immunol,,,True
f8f49888663fdad58dabb5d7f9f8556b36d34587,PMC,"Estimating the Diversity, Completeness, and Cross-Reactivity of the T Cell Repertoire",http://dx.doi.org/10.3389/fimmu.2013.00485,PMC3872652,24421780,CC BY,"In order to recognize and combat a diverse array of pathogens the immune system has a large repertoire of T cells having unique T cell receptors (TCRs) with only a few clones specific for any given antigen. We discuss how the number of different possible TCRs encoded in the genome (the potential repertoire) and the number of different TCRs present in an individual (the realized repertoire) can be measured. One puzzle is that the potential repertoire greatly exceeds the realized diversity of naïve T cells within any individual. We show that the existing hypotheses fail to explain why the immune system has the potential to generate far more diversity than is used in an individual, and propose an alternative hypothesis of “evolutionary sloppiness.” Another immunological puzzle is why mice and humans have similar repertoires even though humans have over 1000-fold more T cells. We discuss how the idea of the “protecton,” the smallest unit of protection, might explain this discrepancy and estimate the size of “protecton” based on available precursor frequencies data. We then consider T cell cross-reactivity – the ability of a T cell clone to respond to more than one epitope. We extend existing calculations to estimate the extent of expected cross-reactivity between the responses to different pathogens. Our results are consistent with two observations: a low probability of observing cross-reactivity between the immune responses to two randomly chosen pathogens; and the ensemble of memory cells being sufficiently diverse to generate cross-reactive responses to new pathogens.",2013 Dec 26,"['Zarnitsyna, Veronika I.', 'Evavold, Brian D.', 'Schoettle, Louis N.', 'Blattman, Joseph N.', 'Antia, Rustom']",Front Immunol,,,True
f7740a58d95fb643e40af517b3da5a3d925edb50,PMC,Aptamer-Based Therapeutics: New Approaches to Combat Human Viral Diseases,http://dx.doi.org/10.3390/ph6121507,PMC3873675,24287493,CC BY,"Viruses replicate inside the cells of an organism and continuously evolve to contend with an ever-changing environment. Many life-threatening diseases, such as AIDS, SARS, hepatitis and some cancers, are caused by viruses. Because viruses have small genome sizes and high mutability, there is currently a lack of and an urgent need for effective treatment for many viral pathogens. One approach that has recently received much attention is aptamer-based therapeutics. Aptamer technology has high target specificity and versatility, i.e., any viral proteins could potentially be targeted. Consequently, new aptamer-based therapeutics have the potential to lead a revolution in the development of anti-infective drugs. Additionally, aptamers can potentially bind any targets and any pathogen that is theoretically amenable to rapid targeting, making aptamers invaluable tools for treating a wide range of diseases. This review will provide a broad, comprehensive overview of viral therapies that use aptamers. The aptamer selection process will be described, followed by an explanation of the potential for treating virus infection by aptamers. Recent progress and prospective use of aptamers against a large variety of human viruses, such as HIV-1, HCV, HBV, SCoV, Rabies virus, HPV, HSV and influenza virus, with particular focus on clinical development of aptamers will also be described. Finally, we will discuss the challenges of advancing antiviral aptamer therapeutics and prospects for future success.",2013 Nov 25,"['Shum, Ka-To', 'Zhou, Jiehua', 'Rossi, John J.']",Pharmaceuticals (Basel),,,True
25affabb80bcf3e1a60c00fc09fd5d2e8f89ec48,PMC,Do Intensive Care Data on Respiratory Infections Reflect Influenza Epidemics?,http://dx.doi.org/10.1371/journal.pone.0083854,PMC3877112,24391837,CC BY,"OBJECTIVES: Severe influenza can lead to Intensive Care Unit (ICU) admission. We explored whether ICU data reflect influenza like illness (ILI) activity in the general population, and whether ICU respiratory infections can predict influenza epidemics. METHODS: We calculated the time lag and correlation between ILI incidence (from ILI sentinel surveillance, based on general practitioners (GP) consultations) and percentages of ICU admissions with a respiratory infection (from the Dutch National Intensive Care Registry) over the years 2003–2011. In addition, ICU data of the first three years was used to build three regression models to predict the start and end of influenza epidemics in the years thereafter, one to three weeks ahead. The predicted start and end of influenza epidemics were compared with observed start and end of such epidemics according to the incidence of ILI. RESULTS: Peaks in respiratory ICU admissions lasted longer than peaks in ILI incidence rates. Increases in ICU admissions occurred on average two days earlier compared to ILI. Predicting influenza epidemics one, two, or three weeks ahead yielded positive predictive values ranging from 0.52 to 0.78, and sensitivities from 0.34 to 0.51. CONCLUSIONS: ICU data was associated with ILI activity, with increases in ICU data often occurring earlier and for a longer time period. However, in the Netherlands, predicting influenza epidemics in the general population using ICU data was imprecise, with low positive predictive values and sensitivities.",2013 Dec 31,"['Koetsier, Antonie', 'van Asten, Liselotte', 'Dijkstra, Frederika', 'van der Hoek, Wim', 'Snijders, Bianca E.', 'van den Wijngaard, Cees C.', 'Boshuizen, Hendriek C.', 'Donker, Gé A.', 'de Lange, Dylan W.', 'de Keizer, Nicolette F.', 'Peek, Niels']",PLoS One,,,True
a0916fa29144e650632aba916141809195ab6809,PMC,An IDEA for Short Term Outbreak Projection: Nearcasting Using the Basic Reproduction Number,http://dx.doi.org/10.1371/journal.pone.0083622,PMC3877403,24391797,CC BY,"BACKGROUND: Communicable disease outbreaks of novel or existing pathogens threaten human health around the globe. It would be desirable to rapidly characterize such outbreaks and develop accurate projections of their duration and cumulative size even when limited preliminary data are available. Here we develop a mathematical model to aid public health authorities in tracking the expansion and contraction of outbreaks with explicit representation of factors (other than population immunity) that may slow epidemic growth. METHODOLOGY: The Incidence Decay and Exponential Adjustment (IDEA) model is a parsimonious function that uses the basic reproduction number R(0), along with a discounting factor to project the growth of outbreaks using only basic epidemiological information (e.g., daily incidence counts). PRINCIPAL FINDINGS: Compared to simulated data, IDEA provides highly accurate estimates of total size and duration for a given outbreak when R(0) is low or moderate, and also identifies turning points or new waves. When tested with an outbreak of pandemic influenza A (H1N1), the model generates estimated incidence at the i+1(th) serial interval using data from the i(th) serial interval within an average of 20% of actual incidence. CONCLUSIONS AND SIGNIFICANCE: This model for communicable disease outbreaks provides rapid assessments of outbreak growth and public health interventions. Further evaluation in the context of real-world outbreaks will establish the utility of IDEA as a tool for front-line epidemiologists.",2013 Dec 31,"['Fisman, David N.', 'Hauck, Tanya S.', 'Tuite, Ashleigh R.', 'Greer, Amy L.']",PLoS One,,,True
7b6a0cdab144889035b432119a497eb9cad5b9cd,PMC,"Information needs and seeking behaviour among health professionals working at public hospital and health centres in Bahir Dar, Ethiopia",http://dx.doi.org/10.1186/1472-6963-13-534,PMC3877973,24373296,CC BY,"BACKGROUND: Universal access to information for health professionals is a need to achieve “health for all strategy.” A large proportion of the population including health professionals have limited access to health information in resource limited countries. The aim of this study is to assess information needs among Ethiopian health professionals. METHODS: A cross sectional quantitative study design complemented with qualitative method was conducted among 350 health care workers in Feburary26-June5/2012. Pretested self-administered questionnaire and observation checklist were used to collect data on different variables. Data entry and data analysis were done using Epi-Info version 3.5.1 and by SPSS version19, respectively. Descriptive statistics and multivariate regression analyses were applied to describe study objectives and identify the determinants of information seeking behaviours respectively. Odds ratio with 95% CI was used to assess the association between a factor and an outcome variable. RESULTS: The majority of the respondents acknowledged the need of health information to their routine activities. About 54.0% of respondents lacked access to health information. Only 42.8% of respondents have access to internet sources. Important barriers to access information were geographical, organizational, personal, economic, educational status and time. About 58.0% of the respondents accessed information by referring their hard copies and asking senior staff. Age, sex, income, computer literacy and access, patient size, work experience and working site were significantly associated with information needs and seeking behaviour. CONCLUSIONS: The health information seeking behaviour of health professional was significant. The heaklth facilities had neither informationcenter such as library, nor internet facilities. Conducting training on managing health information, accessing computer and improving infrastructures are important interventions to facilitate evidence based descions.",2013 Dec 27,"['Andualem, Mulusew', 'Kebede, Gashaw', 'Kumie, Abera']",BMC Health Serv Res,,,True
97c615d915000b15e55f71d20e045bf939c6bca5,PMC,In-vitro renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during Middle East Respiratory Syndrome (MERS) Coronavirus infection,http://dx.doi.org/10.1186/1743-422X-10-359,PMC3878046,24364985,CC BY,"BACKGROUND: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes symptoms similar to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), yet involving an additional component of acute renal failure (ARF) according to several published case reports. Impairment of the kidney is not typically seen in Coronavirus infections. The role of kidney infection in MERS is not understood. FINDINGS: A systematic review of communicated and peer-reviewed case reports revealed differences in descriptions of kidney involvement in MERS versus SARS patients. In particular, ARF in MERS patients occurred considerably earlier after a median time to onset of 11 days (SD ±2,0 days) as opposed to 20 days for SARS, according to the literature. In-situ histological staining of the respective cellular receptors for MERS- and SARS-Coronavirus showed highly similar staining patterns with a focus of a receptor-specific signal in kidney epithelial cells. Comparative infection experiments with SARS- and MERS-CoV in primary human kidney cells versus primary human bronchial epithelial cells showed cytopathogenic infection only in kidney cells, and only if infected with MERS-CoV. Kidney epithelial cells produced almost 1000-fold more infectious MERS-CoV progeny than bronchial epithelial cells, while only a small difference was seen between cell types when infected with SARS-CoV. CONCLUSION: Epidemiological studies should analyze kidney impairment and its characteristics in MERS-CoV. Virus replication in the kidney with potential shedding in urine might constitute a way of transmission, and could explain untraceable transmission chains leading to new cases. Individual patients might benefit from early induction of renoprotective treatment.",2013 Dec 23,"['Eckerle, Isabella', 'Müller, Marcel A', 'Kallies, Stephan', 'Gotthardt, Daniel N', 'Drosten, Christian']",Virol J,,,True
d215fd9c30298cb374b6c9cbec60269c91255fcf,PMC,Chinese social media reaction to the MERS-CoV and avian influenza A(H7N9) outbreaks,http://dx.doi.org/10.1186/2049-9957-2-31,PMC3878123,24359669,CC BY,"BACKGROUND: As internet and social media use have skyrocketed, epidemiologists have begun to use online data such as Google query data and Twitter trends to track the activity levels of influenza and other infectious diseases. In China, Weibo is an extremely popular microblogging site that is equivalent to Twitter. Capitalizing on the wealth of public opinion data contained in posts on Weibo, this study used Weibo as a measure of the Chinese people’s reactions to two different outbreaks: the 2012 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreak, and the 2013 outbreak of human infection of avian influenza A(H7N9) in China. METHODS: Keyword searches were performed in Weibo data collected by The University of Hong Kong’s Weiboscope project. Baseline values were determined for each keyword and reaction values per million posts in the days after outbreak information was released to the public. RESULTS: The results show that the Chinese people reacted significantly to both outbreaks online, where their social media reaction was two orders of magnitude stronger to the H7N9 influenza outbreak that happened in China than the MERS-CoV outbreak that was far away from China. CONCLUSIONS: These results demonstrate that social media could be a useful measure of public awareness and reaction to disease outbreak information released by health authorities.",2013 Dec 20,"['Fung, Isaac Chun-Hai', 'Fu, King-Wa', 'Ying, Yuchen', 'Schaible, Braydon', 'Hao, Yi', 'Chan, Chung-Hong', 'Tse, Zion Tsz-Ho']",Infect Dis Poverty,,,True
d2e396c2837b42c757e8b87e9c54a9e780324e97,PMC,Chinese social media reaction to the MERS-CoV and avian influenza A(H7N9) outbreaks,http://dx.doi.org/10.1186/2049-9957-2-31,PMC3878123,24359669,CC BY,"BACKGROUND: As internet and social media use have skyrocketed, epidemiologists have begun to use online data such as Google query data and Twitter trends to track the activity levels of influenza and other infectious diseases. In China, Weibo is an extremely popular microblogging site that is equivalent to Twitter. Capitalizing on the wealth of public opinion data contained in posts on Weibo, this study used Weibo as a measure of the Chinese people’s reactions to two different outbreaks: the 2012 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreak, and the 2013 outbreak of human infection of avian influenza A(H7N9) in China. METHODS: Keyword searches were performed in Weibo data collected by The University of Hong Kong’s Weiboscope project. Baseline values were determined for each keyword and reaction values per million posts in the days after outbreak information was released to the public. RESULTS: The results show that the Chinese people reacted significantly to both outbreaks online, where their social media reaction was two orders of magnitude stronger to the H7N9 influenza outbreak that happened in China than the MERS-CoV outbreak that was far away from China. CONCLUSIONS: These results demonstrate that social media could be a useful measure of public awareness and reaction to disease outbreak information released by health authorities.",2013 Dec 20,"['Fung, Isaac Chun-Hai', 'Fu, King-Wa', 'Ying, Yuchen', 'Schaible, Braydon', 'Hao, Yi', 'Chan, Chung-Hong', 'Tse, Zion Tsz-Ho']",Infect Dis Poverty,,,False
4c7cbcc5bec46c8c956a8f05adab670eb353cc30,PMC,Chinese social media reaction to the MERS-CoV and avian influenza A(H7N9) outbreaks,http://dx.doi.org/10.1186/2049-9957-2-31,PMC3878123,24359669,CC BY,"BACKGROUND: As internet and social media use have skyrocketed, epidemiologists have begun to use online data such as Google query data and Twitter trends to track the activity levels of influenza and other infectious diseases. In China, Weibo is an extremely popular microblogging site that is equivalent to Twitter. Capitalizing on the wealth of public opinion data contained in posts on Weibo, this study used Weibo as a measure of the Chinese people’s reactions to two different outbreaks: the 2012 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreak, and the 2013 outbreak of human infection of avian influenza A(H7N9) in China. METHODS: Keyword searches were performed in Weibo data collected by The University of Hong Kong’s Weiboscope project. Baseline values were determined for each keyword and reaction values per million posts in the days after outbreak information was released to the public. RESULTS: The results show that the Chinese people reacted significantly to both outbreaks online, where their social media reaction was two orders of magnitude stronger to the H7N9 influenza outbreak that happened in China than the MERS-CoV outbreak that was far away from China. CONCLUSIONS: These results demonstrate that social media could be a useful measure of public awareness and reaction to disease outbreak information released by health authorities.",2013 Dec 20,"['Fung, Isaac Chun-Hai', 'Fu, King-Wa', 'Ying, Yuchen', 'Schaible, Braydon', 'Hao, Yi', 'Chan, Chung-Hong', 'Tse, Zion Tsz-Ho']",Infect Dis Poverty,,,True
33019198857c41e85955b2b731077ab3ea57c85b,PMC,Lineage specific antigenic differences in porcine torovirus hemagglutinin-esterase (PToV-HE) protein,http://dx.doi.org/10.1186/1297-9716-44-126,PMC3878402,24364900,CC BY,"Hemagglutinin-esterases (HE) are viral envelope proteins present in some members from the toro-, corona- and orthomyxovirus families, all related with enteric and/or respiratory tract infections. HE proteins mediate reversible binding to sialic acid receptor determinants, very abundant glycan residues in the enteric and respiratory tracts. The role of the HE protein during the torovirus infection cycle remains unknown, although it is believed to be important in the natural infection process. The phylogenetic analysis of HE coding sequences from porcine torovirus (PToV) field strains revealed the existence of two distinct HE lineages. In a previous study, PToV virus strains with HE proteins from the two lineages were found coexisting in a pig herd, and they were even obtained from the same animal at two consecutive sampling time points. In this work, we report antigenic differences between the two HE lineages, and discuss the possible implications that the coexistence of viruses belonging to both lineages might have on the spread and sustainment of PToV infection in the farms.",2013 Dec 23,"['Pignatelli, Jaime', 'Alonso-Padilla, Julio', 'Rodríguez, Dolores']",Vet Res,,,True
753b8924471c5747cc1600e92a4cfae5d3584439,PMC,Lineage specific antigenic differences in porcine torovirus hemagglutinin-esterase (PToV-HE) protein,http://dx.doi.org/10.1186/1297-9716-44-126,PMC3878402,24364900,CC BY,"Hemagglutinin-esterases (HE) are viral envelope proteins present in some members from the toro-, corona- and orthomyxovirus families, all related with enteric and/or respiratory tract infections. HE proteins mediate reversible binding to sialic acid receptor determinants, very abundant glycan residues in the enteric and respiratory tracts. The role of the HE protein during the torovirus infection cycle remains unknown, although it is believed to be important in the natural infection process. The phylogenetic analysis of HE coding sequences from porcine torovirus (PToV) field strains revealed the existence of two distinct HE lineages. In a previous study, PToV virus strains with HE proteins from the two lineages were found coexisting in a pig herd, and they were even obtained from the same animal at two consecutive sampling time points. In this work, we report antigenic differences between the two HE lineages, and discuss the possible implications that the coexistence of viruses belonging to both lineages might have on the spread and sustainment of PToV infection in the farms.",2013 Dec 23,"['Pignatelli, Jaime', 'Alonso-Padilla, Julio', 'Rodríguez, Dolores']",Vet Res,,,False
d23a5e1b6a5c6036c3e45e7c6d9019a59ddfd6bd,PMC,Minimizing the threat of pandemic emergence from avian influenza in poultry systems,http://dx.doi.org/10.1186/1471-2334-13-592,PMC3878446,24341669,CC BY,"BACKGROUND: Live-animal markets are a culturally important feature of meat distribution chains in many populations, yet they provide an opportunity for the maintenance and transmission of potentially emergent zoonotic pathogens. The ongoing human outbreak of avian H7N9 in China highlights the need for increased surveillance and control in these live-bird markets (LBMs). DISCUSSION: Closure of retail markets in affected areas rapidly decreased human cases to rare, sporadic occurrence, but little attention has been paid thus far to the role of upstream elements of the poultry distribution chain such as wholesale markets. This could partly explain why transmission in poultry populations has not been eliminated more broadly. We present surveillance data from both wholesale live-bird markets (wLBMs) and rLBMs in Shantou, China (from 2004–2006), and call on disease-dynamic theory to illustrate why closing rLBMs has only minor effects on the overall volume of transmission. We show that the length of time birds stay in rLBMs can severely limit transmission there, but that the system-wide effect may be reduced substantially by high levels of transmission upstream of retail markets. SUMMARY: Management plans that minimize transmission throughout the entire poultry supply chain are essential for minimizing exposure to the public. These include reducing stay-time of birds in markets to 1 day, standardizing poultry supply chains to limit transmission in pre-retail settings, and monitoring strains with epidemiological traits that pose a high risk of emergence. These actions will further limit human exposure to extant viruses and reduce the likelihood of the emergence of novel strains by decreasing the overall volume of transmission.",2013 Dec 16,"['Pepin, Kim M', 'Lloyd-Smith, James O', 'Webb, Colleen T', 'Holcomb, Karen', 'Zhu, Huachen', 'Guan, Yi', 'Riley, Steven']",BMC Infect Dis,,,True
8df741c3cb3a548994916cbc0db540c43f374bc7,PMC,Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation,http://dx.doi.org/10.1186/1756-8722-6-94,PMC3878524,24341630,CC BY,"Viral infections are important causes of morbidity and mortality after allogeneic stem cell hematopoietic transplantation (allo-HSCT). Although most viral infections present with asymptomatic or subclinical manifestations, viruses may result in fatal complications in severe immunocompromised recipients. Reactivation of latent viruses, such as herpesviruses, is frequent during the immunosuppression that occurs with allo-HSCT. Viruses acquired from community, such as the respiratory and gastrointestinal viruses, are also important pathogens of post-transplant viral diseases. Currently, molecular diagnostic methods have replaced or supplemented traditional methods, such as viral culture and antigen detection, in diagnosis of viral infections. The utilization of polymerase chain reaction facilitates the early diagnosis. In view of lacking efficacious agents for treatment of viral diseases, prevention of viral infections is extremely valuable. Application of prophylactic strategies including preemptive therapy reduces viral infections and diseases. Adoptive cellular therapy for restoring virus-specific immunity is a promising method in the treatment of viral diseases.",2013 Dec 17,"['Lin, Ren', 'Liu, Qifa']",J Hematol Oncol,,,True
5977507d38a03786e12e8e48cda0b431871af042,PMC,Single injection recombinant vesicular stomatitis virus vaccines protect ferrets against lethal Nipah virus disease,http://dx.doi.org/10.1186/1743-422X-10-353,PMC3878732,24330654,CC BY,"BACKGROUND: Nipah virus (NiV) is a highly pathogenic zoonotic agent in the family Paramyxoviridae that is maintained in nature by bats. Outbreaks have occurred in Malaysia, Singapore, India, and Bangladesh and have been associated with 40 to 75% case fatality rates. There are currently no vaccines or postexposure treatments licensed for combating human NiV infection. METHODS AND RESULTS: Four groups of ferrets received a single vaccination with different recombinant vesicular stomatitis virus vectors expressing: Group 1, control with no glycoprotein; Group 2, the NiV fusion protein (F); Group 3, the NiV attachment protein (G); and Group 4, a combination of the NiV F and G proteins. Animals were challenged intranasally with NiV 28 days after vaccination. Control ferrets in Group 1 showed characteristic clinical signs of NiV disease including respiratory distress, neurological disorders, viral load in blood and tissues, and gross lesions and antigen in target tissues; all animals in this group succumbed to infection by day 8. Importantly, all specifically vaccinated ferrets in Groups 2-4 showed no evidence of clinical illness and survived challenged. All animals in these groups developed anti-NiV F and/or G IgG and neutralizing antibody titers. While NiV RNA was detected in blood at day 6 post challenge in animals from Groups 2-4, the levels were orders of magnitude lower than animals from control Group 1. CONCLUSIONS: These data show protective efficacy against NiV in a relevant model of human infection. Further development of this technology has the potential to yield effective single injection vaccines for NiV infection.",2013 Dec 13,"['Mire, Chad E', 'Versteeg, Krista M', 'Cross, Robert W', 'Agans, Krystle N', 'Fenton, Karla A', 'Whitt, Michael A', 'Geisbert, Thomas W']",Virol J,,,True
39b4ca41bed615d00441db0664ce67e473e74ba5,PMC,VIRsiRNApred: a web server for predicting inhibition efficacy of siRNAs targeting human viruses,http://dx.doi.org/10.1186/1479-5876-11-305,PMC3878835,24330765,CC BY,"BACKGROUND: Selection of effective viral siRNA is an indispensable step in the development of siRNA based antiviral therapeutics. Despite immense potential, a viral siRNA efficacy prediction algorithm is still not available. Moreover, performances of the existing general mammalian siRNA efficacy predictors are not satisfactory for viral siRNAs. Therefore, we have developed “VIRsiRNApred” a support vector machine (SVM) based method for predicting the efficacy of viral siRNA. METHODS: In the present study, we have employed a new dataset of 1725 viral siRNAs with experimentally verified quantitative efficacies tested under heterogeneous experimental conditions and targeting as many as 37 important human viruses including HIV, Influenza, HCV, HBV, SARS etc. These siRNAs were divided into training (T(1380)) and validation (V(345)) datasets. Important siRNA sequence features including mono to penta nucleotide frequencies, binary pattern, thermodynamic properties and secondary structure were employed for model development. RESULTS: During 10-fold cross validation on T(1380) using hybrid approach, we achieved a maximum Pearson Correlation Coefficient (PCC) of 0.55 between predicted and actual efficacy of viral siRNAs. On V(345) independent dataset, our best model achieved a maximum correlation of 0.50 while existing general siRNA prediction methods showed PCC from 0.05 to 0.18. However, using leave one out cross validation PCC was improved to 0.58 and 0.55 on training and validation datasets respectively. SVM performed better than other machine learning techniques used like ANN, KNN and REP Tree. CONCLUSION: VIRsiRNApred is the first algorithm for predicting inhibition efficacy of viral siRNAs which is developed using experimentally verified viral siRNAs. We hope this algorithm would be useful in predicting highly potent viral siRNA to aid siRNA based antiviral therapeutics development. The web server is freely available at http://crdd.osdd.net/servers/virsirnapred/.",2013 Dec 11,"['Qureshi, Abid', 'Thakur, Nishant', 'Kumar, Manoj']",J Transl Med,,,True
15d52271667c76c6db91907ad72ecb65fb88ec84,PMC,Phylogeography of influenza A H5N1 clade 2.2.1.1 in Egypt,http://dx.doi.org/10.1186/1471-2164-14-871,PMC3878885,24325606,CC BY,"BACKGROUND: Influenza A H5N1 has killed millions of birds and raises serious public health concern because of its potential to spread to humans and cause a global pandemic. While the early focus was in Asia, recent evidence suggests that Egypt is a new epicenter for the disease. This includes characterization of a variant clade 2.2.1.1, which has been found almost exclusively in Egypt. We analyzed 226 HA and 92 NA sequences with an emphasis on the H5N1 2.2.1.1 strains in Egypt using a Bayesian discrete phylogeography approach. This allowed modeling of virus dispersion between Egyptian governorates including the most likely origin. RESULTS: Phylogeography models of hemagglutinin (HA) and neuraminidase (NA) suggest Ash Sharqiyah as the origin of virus spread, however the support is weak based on Kullback–Leibler values of 0.09 for HA and 0.01 for NA. Association Index (AI) values and Parsimony Scores (PS) were significant (p-value < 0.05), indicating that dispersion of H5N1 in Egypt was geographically structured. In addition, the Ash Sharqiyah to Al Gharbiyah and Al Fayyum to Al Qalyubiyah routes had the strongest statistical support. CONCLUSION: We found that the majority of routes with strong statistical support were in the heavily populated Delta region. In particular, the Al Qalyubiyah governorate appears to represent a popular location for virus transition as it represented a large portion of branches in both trees. However, there remains uncertainty about virus dispersion to and from this location and thus more research needs to be conducted in order to examine this. Phylogeography can highlight the drivers of H5N1 emergence and spread. This knowledge can be used to target public health efforts to reduce morbidity and mortality. For Egypt, future work should focus on using data about vaccination and live bird markets in phylogeography models to study their impact on H5N1 diffusion within the country.",2013 Dec 10,"['Scotch, Matthew', 'Mei, Changjiang', 'Makonnen, Yilma J', 'Pinto, Julio', 'Ali, AbdelHakim', 'Vegso, Sally', 'Kane, Michael', 'Sarkar, Indra Neil', 'Rabinowitz, Peter']",BMC Genomics,,,True
d2f29c0bf8f5b9bf9d357001a62b42244698b298,PMC,The Gene Expression Profile of Peripheral Blood Mononuclear Cells from EV71-Infected Rhesus Infants and the Significance in Viral Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0083766,PMC3879270,24392094,CC BY,"Enterovirus 71 (EV71) is the major pathogen responsible for fatal hand, foot and mouth disease (HFMD). Our previous work reported on an EV71-infected rhesus monkey infant model that presented with histo-pathologic changes of the central nervous system (CNS) and lungs. This study is focused on the correlated modulation of gene expression in the peripheral blood mononuclear cells (PBMCs) from EV71-infected rhesus monkey infants. The expression of more than 500 functional genes associated with multiple pathways was modulated. The expression of genes associated with immune inflammatory responses was up-regulated during the period from days 4 to 10 post-infection. The expression of two genes (TAC1 and IL17A), which play major roles in inflammatory reactions, was remarkably up-regulated during the infection period. Furthermore, a higher expression level of the TAC1 gene was identified in the CNS compared to the lungs, but a high expression level of the IL-17A gene was observed in the lungs and not in the CNS. The results of this study suggest at least two facts about EV71 infection, which are that: the TAC1 gene that encodes substance P and neurokinin-A is present in both PBMCs and the hypothalamus; and the up-regulation of IL-17A is sustained in the peripheral blood.",2014 Jan 2,"['Zhang, Ying', 'Yang, Erxia', 'Pu, Jing', 'Liu, Longding', 'Che, Yanchun', 'Wang, Jingjing', 'Liao, Yun', 'Wang, Lichun', 'Ding, Dong', 'Zhao, Ting', 'Ma, Na', 'Song, Ming', 'Wang, Xi', 'Shen, Dong', 'Tang, Donghong', 'Huang, Hongtai', 'Zhang, Zhixiao', 'Chen, Dai', 'Feng, Mingfei', 'Li, Qihan']",PLoS One,,,True
8fa2be5d5abb0473dda3892cf6f42a318f87b39b,PMC,Transcriptome Analysis of Houttuynia cordata Thunb. by Illumina Paired-End RNA Sequencing and SSR Marker Discovery,http://dx.doi.org/10.1371/journal.pone.0084105,PMC3879290,24392108,CC BY,"BACKGROUND: Houttuynia cordata Thunb. is an important traditional medical herb in China and other Asian countries, with high medicinal and economic value. However, a lack of available genomic information has become a limitation for research on this species. Thus, we carried out high-throughput transcriptomic sequencing of H. cordata to generate an enormous transcriptome sequence dataset for gene discovery and molecular marker development. PRINCIPAL FINDINGS: Illumina paired-end sequencing technology produced over 56 million sequencing reads from H. cordata mRNA. Subsequent de novo assembly yielded 63,954 unigenes, 39,982 (62.52%) and 26,122 (40.84%) of which had significant similarity to proteins in the NCBI nonredundant protein and Swiss-Prot databases (E-value <10(−5)), respectively. Of these annotated unigenes, 30,131 and 15,363 unigenes were assigned to gene ontology categories and clusters of orthologous groups, respectively. In addition, 24,434 (38.21%) unigenes were mapped onto 128 pathways using the KEGG pathway database and 17,964 (44.93%) unigenes showed homology to Vitis vinifera (Vitaceae) genes in BLASTx analysis. Furthermore, 4,800 cDNA SSRs were identified as potential molecular markers. Fifty primer pairs were randomly selected to detect polymorphism among 30 samples of H. cordata; 43 (86%) produced fragments of expected size, suggesting that the unigenes were suitable for specific primer design and of high quality, and the SSR marker could be widely used in marker-assisted selection and molecular breeding of H. cordata in the future. CONCLUSIONS: This is the first application of Illumina paired-end sequencing technology to investigate the whole transcriptome of H. cordata and to assemble RNA-seq reads without a reference genome. These data should help researchers investigating the evolution and biological processes of this species. The SSR markers developed can be used for construction of high-resolution genetic linkage maps and for gene-based association analyses in H. cordata. This work will enable future functional genomic research and research into the distinctive active constituents of this genus.",2014 Jan 2,"['Wei, Lin', 'Li, Shenghua', 'Liu, Shenggui', 'He, Anna', 'Wang, Dan', 'Wang, Jie', 'Tang, Yulian', 'Wu, Xianjin']",PLoS One,,,True
293854bf36effa5c8080201deaa19b213d4465c9,PMC,Effect of facemasks on empathy and relational continuity: a randomised controlled trial in primary care,http://dx.doi.org/10.1186/1471-2296-14-200,PMC3879648,24364989,CC BY,"BACKGROUND: There is limited evidence to support the use of facemasks in preventing infection for primary care professionals. Negative effects on communication has been suggested when the physician wears a facemask. As communication skills and doctor patient relationship are essential to primary care consultations, the effects of doctor’s facemask wearing were explored. METHOD: A randomised controlled study was conducted in primary care to explore the effects of doctors wearing facemasks on patients’ perception of doctors’ empathy, patient enablement and patient satisfaction. Primary care doctors were randomized to mask wearing and non mask wearing clinical consultations in public primary care clinics in Hong Kong. Patients’ views were gathered using the Consultation and Relational Empathy (CARE) Measure, Patient Enablement Instrument (PEI) and an overall satisfaction rating scale. The effects of face mask wearing were investigated using multilevel (hierarchical) modelling. RESULTS: 1,030 patients were randomised to doctor-mask wearing consultations (n = 514) and non mask wearing consultations (n = 516). A significant and negative effect was found in the patients’ perception of the doctors’ empathy (CARE score reduction -0.98, p-value = 0.04). In the more established doctor-patient relationship, the effect of doctors’ mask wearing was more pronounced (CARE score reduction -5.67, p-value = 0.03). CONCLUSION: This study demonstrates that when doctors wearing a facemask during consultations, this has a significant negative impact on the patient’s perceived empathy and diminish the positive effects of relational continuity. Consideration should be taken in planning appropriate use of facemasks in infectious disease policy for primary care and other healthcare professionals at a national, local or practice level. CLINICAL TRIAL REGISTRATION: This trial was registered on Chinese Clinical Trial Register (ChiCTR). Registration no.: ChiCTR-TTRCC-12002519. URL: http://www.chictr.org/en/proj/show.aspx?proj=3486. Due to administrative error, registration of trial did not take place until after the trial started on 1(st) August 2011 and registration number was released on 21(st) September 2012.",2013 Dec 24,"['Wong, Carmen Ka Man', 'Yip, Benjamin Hon Kei', 'Mercer, Stewart', 'Griffiths, Sian', 'Kung, Kenny', 'Wong, Martin Chi-sang', 'Chor, Josette', 'Wong, Samuel Yeung-shan']",BMC Fam Pract,,,True
c1e4465687748c1d03b1c648b1558d1051859b5a,PMC,A cross-sectional study of the clinical characteristics of hospitalized children with community-acquired pneumonia in eight eastern cities in China,http://dx.doi.org/10.1186/1472-6882-13-367,PMC3880031,24364897,CC BY,"BACKGROUND: Community-acquired pneumonia in children is common in China. To understand current clinical characteristics and practice, we conducted a cross-sectional study to analyze quality of care on childhood pneumonia in eight eastern cities in China. METHODS: Consecutive hospital records between January 1, 2010 and December 31, 2010 were collected from 13 traditional Chinese medicine (TCM) and western medicine (WM) hospitals in February, May, August, and November (25 cases per season, 100 cases over the year), respectively. A predesigned case report form was used to extract data from the hospital medical records. RESULTS: A total of 1298 cases were collected and analyzed. Symptoms and signs upon admission at TCM and WM hospitals were cough (99.3% vs. 98.6%), rales (84.8% vs. 75.0%), phlegm (83.3% vs. 49.1%), and fever (74.9% vs. 84.0%) in frequency. Patients admitted to WM hospitals had symptoms and signs for a longer period prior to admission than patients admitted to TCM hospitals. Testing to identify etiologic agents was performed in 1140 cases (88.4%). Intravenous antibiotics were administered in 99.3% (595/598) of cases in TCM hospitals and in 98.6% (699/700) of cases in WM hospitals. Besides, Chinese herbal extract injection was used more frequently in TCM hospitals (491 cases, 82.1%) than in WM hospitals (212 cases, 30.3%) (p < 0.01). At discharge, 818 cases (63.0%) were clinically cured, with a significant difference between the cure rates in TCM (87.6%) and WM hospitals (42.0%) (OR = 9.8, 95% confidence interval (CI): 7.3 ~ 12.9, p < 0.01). Pathogen and previous medical history were more likely associated with the disappearance of rales (OR = 7.2, 95% CI: 4.8 ~ 10.9). Adverse effects were not reported from the medical records. CONCLUSIONS: Intravenous use of antibiotics is highly prevalent in children with community-acquired pneumonia regardless of aetiology. There was difference between TCM and WM hospitals with regard to symptom profile and the use of antibiotics. Intravenous use of herbal injection was higher in TCM hospitals than in WM hospitals. Most of the cases were diagnosed based on clinical signs and symptoms without sufficient confirmation of aetiology. Audit of current practice is urgently needed to improve care.",2013 Dec 23,"['Wang, Xue-Feng', 'Liu, Jian-Ping', 'Shen, Kun-Ling', 'Ma, Rong', 'Cui, Zhen-Ze', 'Deng, Li', 'Shang, Yun-Xiao', 'Zhao, De-Yu', 'Wang, Li-Bo', 'Wan, Li-Ya', 'Sun, Yi-Qiu', 'Li, Yan-Ning', 'Jiang, Zhi-Yan', 'Xu, Hua', 'Li, Xin-Min', 'Wu, Zhen-Qi', 'Liu, Zhao-Lan', 'Hu, Ying-Hui', 'Huang, Yan', 'He, Chun-Hui', 'Zhang, Han', 'Jiang, Yong-Hong', 'Liu, Hua', 'Wang, Zi']",BMC Complement Altern Med,,,True
14a0b8d9f05d4baef14cfa9178748cb9d504d523,PMC,Design and Experimental Approach to the Construction of a Human Signal-Molecule-Profiling Database,http://dx.doi.org/10.3390/ijerph10126887,PMC3881147,24351788,CC BY,"The human signal-molecule-profiling database (HSMPD) is designed as a prospective medical database for translational bioinformatics (TBI). To explore the feasibility of low-cost database construction, we studied the roadmap of HSMPD. A HSMPD-oriented tool, called “signal-molecule-profiling (SMP) chip” was developed for data acquisition, which can be employed in the routine blood tests in hospitals; the results will be stored in the HSMPD system automatically. HSMPD system can provide data services for the TBI community, which generates a stable income to support the data acquisition. The small-scale experimental test was performed in the hospital to verify SMP chips and the demo HSMPD software. One hundred and eighty nine complete SMP records were collected, and the demo HSMPD system was also evaluated in the survey study on patients and doctors. The function of SMP chip was verified, whereas the demo HSMPD software needed to be improved. The survey study showed that patients would only accept free tests of SMP chips when they originally needed blood examinations. The study indicated that the construction of HSMPD relies on the self-motivated cooperation of the TBI community and the traditional healthcare system. The proposed roadmap potentially provides an executable solution to build the HSMPD without high costs.",2013 Dec 9,"['Zhao, Xinyan', 'Dong, Tao']",Int J Environ Res Public Health,,,True
8a5accd8df7fcfcef5fb8b467e2cc8caa7c631a4,PMC,A Neutralization Epitope in the Hepatitis C Virus E2 Glycoprotein Interacts with Host Entry Factor CD81,http://dx.doi.org/10.1371/journal.pone.0084346,PMC3882236,24400084,CC0,"The identification of a specific immunogenic candidate that will effectively activate the appropriate pathway for neutralizing antibody production is fundamental for vaccine design. By using a monoclonal antibody (1H8) that neutralizes HCV in vitro, we have demonstrated here that 1H8 recognized an epitope mapped between residues A524 and W529 of the E2 protein. We also found that the epitope residues A524, P525, Y527 and W529 were crucial for antibody binding, while the residues T526, Y527 and W529 within the same epitope engaged in the interaction with the host entry factor CD81. Furthermore, we detected “1H8-like” antibodies, defined as those with amino acid-specificity similar to 1H8, in the plasma of patients with chronic HCV infection. The time course study of plasma samples from Patient H, a well-characterized case of post-transfusion hepatitis C, showed that “1H8-like” antibodies could be detected in a sample collected almost two years after the initial infection, thus confirming the immunogenicity of this epitope in vivo. The characterization of this neutralization epitope with a function in host entry factor CD81 interaction should enhance our understanding of antibody-mediated neutralization of HCV infections.",2014 Jan 6,"['Zhao, Zhong', 'Zhong, Lilin', 'Elrod, Elizabeth', 'Struble, Evi', 'Ma, Li', 'Yan, Hailing', 'Harman, Christine', 'Deng, Lu', 'Virata-Theimer, Maria Luisa', 'Liu, Peter', 'Alter, Harvey', 'Grakoui, Arash', 'Zhang, Pei']",PLoS One,,,True
372f3a4aac120be6b70f0b3d51481ab2679a6b92,PMC,"Full-Genome Analysis of a Canine Pneumovirus Causing Acute Respiratory Disease in Dogs, Italy",http://dx.doi.org/10.1371/journal.pone.0085220,PMC3882280,24400129,CC BY,"An outbreak of canine infectious respiratory disease (CIRD) associated to canine pneumovirus (CnPnV) infection is reported. The outbreak occurred in a shelter of the Apulia region and involved 37 out of 350 dogs that displayed cough and/or nasal discharge with no evidence of fever. The full-genomic characterisation showed that the causative agent (strain Bari/100-12) was closely related to CnPnVs that have been recently isolated in the USA, as well as to murine pneumovirus, which is responsible for respiratory disease in mice. The present study represents a useful contribution to the knowledge of the pathogenic potential of CnPnV and its association with CIRD in dogs. Further studies will elucidate the pathogenicity and epidemiology of this novel pneumovirus, thus addressing the eventual need for specific vaccines.",2014 Jan 6,"['Decaro, Nicola', 'Pinto, Pierfrancesco', 'Mari, Viviana', 'Elia, Gabriella', 'Larocca, Vittorio', 'Camero, Michele', 'Terio, Valentina', 'Losurdo, Michele', 'Martella, Vito', 'Buonavoglia, Canio']",PLoS One,,,True
4e9183ccee2b50199a61683e3d261417ab182bda,PMC,Viral encephalitis caused by respiratory viruses,http://dx.doi.org/10.1186/1471-2334-13-S1-P78,PMC3882642,,CC BY,,2013 Dec 16,"['Vişan, Angelica', 'Luminos, Monica', 'Vasile, Magda', 'Drăgănescu, Anca', 'Jugulete, Gheorghiță', 'Bilaşco, Anuța', 'Negulescu, Cristina', 'Kouris, Camelia', 'Măntescu, Ruxandra', 'Merişescu, Mădălina Maria', 'Osman, Endis', 'Șchiopu, Sabina', 'Florea, Dragoş', 'Oțelea, Dan']",BMC Infect Dis,,,False
2804ea9b709694627657763fd17564d0323a5dcf,PMC,Multi-omic network signatures of disease,http://dx.doi.org/10.3389/fgene.2013.00309,PMC3882664,24432028,CC BY,"To better understand dynamic disease processes, integrated multi-omic methods are needed, yet comparing different types of omic data remains difficult. Integrative solutions benefit experimenters by eliminating potential biases that come with single omic analysis. We have developed the methods needed to explore whether a relationship exists between co-expression network models built from transcriptomic and proteomic data types, and whether this relationship can be used to improve the disease signature discovery process. A naïve, correlation based method is utilized for comparison. Using publicly available infectious disease time series data, we analyzed the related co-expression structure of the transcriptome and proteome in response to SARS-CoV infection in mice. Transcript and peptide expression data was filtered using quality scores and subset by taking the intersection on mapped Entrez IDs. Using this data set, independent co-expression networks were built. The networks were integrated by constructing a bipartite module graph based on module member overlap, module summary correlation, and correlation to phenotypes of interest. Compared to the module level results, the naïve approach is hindered by a lack of correlation across data types, less significant enrichment results, and little functional overlap across data types. Our module graph approach avoids these problems, resulting in an integrated omic signature of disease progression, which allows prioritization across data types for down-stream experiment planning. Integrated modules exhibited related functional enrichments and could suggest novel interactions in response to infection. These disease and platform-independent methods can be used to realize the full potential of multi-omic network signatures. The data (experiment SM001) are publically available through the NIAID Systems Virology (https://www.systemsvirology.org) and PNNL (http://omics.pnl.gov) web portals. Phenotype data is found in the supplementary information. The ProCoNA package is available as part of Bioconductor 2.13.",2014 Jan 7,"['Gibbs, David L.', 'Gralinski, Lisa', 'Baric, Ralph S.', 'McWeeney, Shannon K.']",Front Genet,,,True
5e8f40e1096456d1b5b0c24b57104bf15f45d37e,PMC,Two Different Conformations in Hepatitis C Virus p7 Protein Account for Proton Transport and Dye Release,http://dx.doi.org/10.1371/journal.pone.0078494,PMC3883635,24409277,CC BY,"The p7 protein from the hepatitis C virus (HCV) is a 63 amino acid long polypeptide that is essential for replication, and is involved in protein trafficking and proton transport. Therefore, p7 is a possible target for antivirals. The consensus model for the channel formed by p7 protein is a hexameric or heptameric oligomer of α-helical hairpin monomers, each having two transmembrane domains, TM1 and TM2, where the N-terminal TM1 would face the lumen of this channel. A reported high-throughput functional assay to search for p7 channel inhibitors is based on carboxyfluorescein (CF) release from liposomes after p7 addition. However, the rationale for the dual ability of p7 to serve as an ion or proton channel in the infected cell, and to permeabilize membranes to large molecules like CF is not clear. We have recreated both activities in vitro, examining the conformation present in these assays using infrared spectroscopy. Our results indicate that an α-helical form of p7, which can transport protons, is not able to elicit CF release. In contrast, membrane permeabilization to CF is observed when p7 contains a high percentage of β-structure, or when using a C-terminal fragment of p7, encompassing TM2. We propose that the reported inhibitory effect of some small compounds, e.g., rimantadine, on both CF release and proton transport can be explained via binding to the membrane-inserted C-terminal half of p7, increasing its rigidity, in a similar way to the influenza A M2-rimantadine interaction.",2014 Jan 7,"['Gan, Siok Wan', 'Surya, Wahyu', 'Vararattanavech, Ardcharaporn', 'Torres, Jaume']",PLoS One,,,True
b0e5a700bc9e8fe25e5c3f2c10976314cb30c150,PMC,Normal Thoracic Radiographic Appearance of the Cynomolgus Monkey (Macaca fascicularis),http://dx.doi.org/10.1371/journal.pone.0084599,PMC3885584,24416248,CC BY,"BACKGROUND: The cynomolgus monkey (Macaca fascicularis) has been increasingly used as a non-human primate model in biomedical research. As establishing baseline thoracic radiography for the cynomolgus monkey is essential, we tested the hypothesis that age and sex may affect the thoracic radiography parameters of this species. METHODS: Here, 697 healthy cynomolgus monkeys were segregated by sex and age (three age groups: 25–36 months, 37–48 months, 49–60 months). The lung length (LL), maximal interior thoracic depth (TD), maximal interior thoracic breadth (TBr), cardiac silhouette breadth (CBr), cardiothoracic ratio (CR), right and left costophrenic angles (RCA and LCA), and right hilar height ratio (R-HHR) were assessed by chest film. Statistical analysis was applied to examine the effect of age, sex, and age × sex interactions. RESULTS: Significant effects by age were shown for LL, TD, TBr, CBr, and CR. Significant effects by sex were found for TD, TBr, CBr, CR, and R-HHR. Significant effects by age × sex were observed for TD, TBr, CBr, and CR. Both TD and TBr increased with age in both sexes, and both were significantly higher in males than in females in the group aged 49–60 months. CBr increased with age and was significantly higher in males than in females across all age groups. CR declined with age and was significantly higher in males than females across all age groups, and CR was similar or slightly higher relative to those previously found in other non-human primate species. As to the other parameters with no significant sex nor age-related differences, the R-HHR was greater than 1.00, and the angulation of bilateral costophrenic angles were sharp. CONCLUSIONS: The thoracic radiographic parameters for the healthy cynomolgus monkey presented here should prove useful in veterinary practice, research involving non-human primate models of respiratory or cardiovascular disorders, and morphological studies on cynomolgus monkeys.",2014 Jan 8,"['Xie, Liang', 'Zhou, Qinming', 'Liu, Shigang', 'Wu, Qingyuan', 'Ji, Yongjia', 'Zhang, Lujun', 'Xu, Fan', 'Gong, Wei', 'Melgiri, Narayan D.', 'Xie, Peng']",PLoS One,,,True
5912189e6ca5053f8e7a2de341c90341f737aa7e,PMC,"Pandemic Influenza Virus 2009 H1N1 and Adenovirus in a High Risk Population of Young Adults: Epidemiology, Comparison of Clinical Presentations, and Coinfection",http://dx.doi.org/10.1371/journal.pone.0085094,PMC3885690,24416345,CC0,"BACKGROUND: In 2009, pandemic H1N1 influenza virus (2009 H1N1) emerged worldwide, causing morbidity and mortality that disproportionately affected young adults. Upper respiratory infection (URI), largely due to adenovirus, is an endemic cause of morbidity in military training. Whether clinical presentations differ or excess morbidity results from coinfection is unclear. METHODS: The Center for Advanced Molecular Detection evaluates epidemiology and rapid diagnostics of respiratory pathogens in trainees with URI. From May 1, 2009, to November 30, 2009, demographic, clinical, and PCR data from throat and nasal specimens for adenovirus and 2009 H1N1 were prospectively collected. RESULTS: 375 trainees with URI enrolled and were tested for both adenovirus and 2009 H1N1 by PCR (median age 20; 89% male). Adenovirus PCR was positive in 72% (96% serotype E-4) and 2009 H1N1 in 20%. Males were more likely to have adenovirus and females more likely to have 2009 H1N1 (p  =  0.047). Subjects with 2009 H1N1 presented an average of 1 week earlier in training, had shorter illness duration before enrollment, less sore throat, diarrhea, and fewer abnormal findings on throat exam. Coryza and cough were more common with 2009 H1N1 compared to adenovirus. Subjects with 2009 H1N1 were less likely to have adenovirus than those without, despite persistently high frequencies of adenovirus detections during peak 2009 H1N1 weeks (15% vs. 83%, p < 0.01). Coinfection with adenovirus and 2009 H1N1 was rare (4%). Rates of hospitalization and pneumonia did not differ between the adenovirus, 2009 H1N1, or coinfected groups. CONCLUSION: Military trainees with 2009 H1N1 vs. adenovirus have differing clinical presentations, and males are more likely to have adenovirus. Despite high frequencies of adenovirus infection, coinfection with adenovirus and 2009 H1N1 is rare and apparently does not result in increased morbidity.",2014 Jan 8,"['Yun, Heather C.', 'Fugate, William H.', 'Murray, Clinton K.', 'Cropper, Thomas L.', 'Lott, Lisa', 'McDonald, J. Matthew']",PLoS One,,,True
239cd6dbc4b75c51256acc527ae69394b891bc1d,PMC,CD13 promotes mesenchymal stem cell-mediated regeneration of ischemic muscle,http://dx.doi.org/10.3389/fphys.2013.00402,PMC3885827,24409152,CC BY,"Mesenchymal stem cells (MSCs) are multipotent, tissue-resident cells that can facilitate tissue regeneration and thus, show great promise as potential therapeutic agents. Functional MSCs have been isolated and characterized from a wide array of adult tissues and are universally identified by the shared expression of a core panel of MSCs markers. One of these markers is the multifunctional cell surface peptidase CD13 that has been shown to be expressed on human and murine MSCs from many tissues. To investigate whether this universal expression indicates a functional role for CD13 in MSC biology we isolated, expanded and characterized MSCs from bone marrow of wild type (WT) and CD13(KO) mice. Characterization of these cells demonstrated that both WT and CD13(KO) MSCs expressed the full complement of MSC markers (CD29, CD44, CD49e, CD105, Sca1), showed comparable proliferation rates and were capable of differentiating toward the adipogenic and osteogenic lineages. However, MSCs lacking CD13 were unable to differentiate into vascular cells, consistent with our previous characterization of CD13 as an angiogenic regulator. Compared to WT MSCs, adhesion and migration on various extracellular matrices of CD13(KO) MSCs were significantly impaired, which correlated with decreased phospho-FAK levels and cytoskeletal alterations. Crosslinking human MSCs with activating CD13 antibodies increased cell adhesion to endothelial monolayers and induced FAK activation in a time dependent manner. In agreement with these in vitro data, intramuscular injection of CD13(KO) MSCs in a model of severe ischemic limb injury resulted in significantly poorer perfusion, decreased ambulation, increased necrosis and impaired vascularization compared to those receiving WT MSCs. This study suggests that CD13 regulates FAK activation to promote MSC adhesion and migration, thus, contributing to MSC-mediated tissue repair. CD13 may present a viable target to enhance the efficacy of mesenchymal stem cell therapies.",2014 Jan 9,"['Rahman, M. Mamunur', 'Subramani, Jaganathan', 'Ghosh, Mallika', 'Denninger, Jiyeon K.', 'Takeda, Kotaro', 'Fong, Guo-Hua', 'Carlson, Morgan E.', 'Shapiro, Linda H.']",Front Physiol,,,True
317f9c2b15b77682a875328e023b5b62a9eb2896,PMC,"Update on the Angiotensin Converting Enzyme 2-Angiotensin (1–7)-Mas Receptor Axis: Fetal Programing, Sex Differences, and Intracellular Pathways",http://dx.doi.org/10.3389/fendo.2013.00201,PMC3886117,24409169,CC BY,"The renin-angiotensin-system (RAS) constitutes an important hormonal system in the physiological regulation of blood pressure. Indeed, dysregulation of the RAS may lead to the development of cardiovascular pathologies including kidney injury. Moreover, the blockade of this system by the inhibition of angiotensin converting enzyme (ACE) or antagonism of the angiotensin type 1 receptor (AT(1)R) constitutes an effective therapeutic regimen. It is now apparent with the identification of multiple components of the RAS that the system is comprised of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS can be defined as the ACE-Ang II-AT(1)R axis that promotes vasoconstriction, sodium retention, and other mechanisms to maintain blood pressure, as well as increased oxidative stress, fibrosis, cellular growth, and inflammation in pathological conditions. In contrast, the non-classical RAS composed of the ACE2-Ang-(1–7)-Mas receptor axis generally opposes the actions of a stimulated Ang II-AT(1)R axis through an increase in nitric oxide and prostaglandins and mediates vasodilation, natriuresis, diuresis, and oxidative stress. Thus, a reduced tone of the Ang-(1–7) system may contribute to these pathologies as well. Moreover, the non-classical RAS components may contribute to the effects of therapeutic blockade of the classical system to reduce blood pressure and attenuate various indices of renal injury. The review considers recent studies on the ACE2-Ang-(1–7)-Mas receptor axis regarding the precursor for Ang-(1–7), the intracellular expression and sex differences of this system, as well as an emerging role of the Ang1-(1–7) pathway in fetal programing events and cardiovascular dysfunction.",2014 Jan 9,"['Chappell, Mark C.', 'Marshall, Allyson C.', 'Alzayadneh, Ebaa M.', 'Shaltout, Hossam A.', 'Diz, Debra I.']",Front Endocrinol (Lausanne),,,True
d12f82f17862869b5118dc55c63929adc6597dd4,PMC,"Immunomorphologic Manifestations in Mice Liver Infected with Influenza A/H5N1, A/Goose/Krasnoozerskoye/627/05 Strain",http://dx.doi.org/10.1155/2013/342686,PMC3886489,24454472,CC BY,"Highly pathogenic avian influenza H5N1 (HPAI H5N1) viruses can infect mammals, including humans, causing severe systemic disease with the inhibition of the immune system and a high mortality rate. In conditions of lymphoid tissue depletion, the liver plays an important role in host defence against viruses. The changes in mice liver infected with HPAI H5N1 virus A/goose/Krasnoozerskoye/627/05 have been studied. It has been shown that the virus persistence in the liver leads to the expression of proinflammatory cytokines (TNF-α, IL-6) and intracellular proteases (lysozyme, cathepsin D, and myeloperoxidase) by Kupffer cells. Defective antiviral response exacerbates destructive processes in the liver accelerating the development of liver failure.",2013 Dec 23,"['Potapova, Oxana V.', 'Sharkova, Tatyana V.', 'Shkurupiy, Vyacheslav A.', 'Shestopalov, Alexander M.']",Clin Dev Immunol,,,True
a30fd6139467d0ef97598274d3d926ddf4623e88,PMC,“Don’t forget the migrants”: exploring preparedness and response strategies to combat the potential spread of MERS-CoV virus through migrant workers in Sri Lanka,http://dx.doi.org/10.12688/f1000research.2-163.v1,PMC3886786,24555078,CC BY,"From September 2012 to July 2013, 81 laboratory-confirmed cases of infection with Middle East respiratory syndrome coronavirus (MERS-CoV), including 45 deaths (a case fatality ratio of 55%) have been reported from eight countries. Human-to-human transmission is now confirmed showing potential for another pandemic of zoonotic disease, with an extremely high mortality rate. Effective surveillance strategies are required in countries with a high influx of migrants from the Middle East to mitigate the probable importation of MERS-CoV. We discuss here the risk of MERS-CoV in major labor sending countries and list the probable strategies for control and prevention of MERS-CoV using Sri Lanka as an example. It is conservatively estimated that 10% of Sri Lanka’s population work as international labor migrants (1.8 to 2 million workers), with 93% residing in the Middle East. An average of 720 workers depart each day, with the majority of these workers (71%) departing to the Kingdom of Saudi Arabia (the country with 81.5% of total MERS-CoV cases). We also describe other inbound migration categories such as tourists and resident visa holders relevant to the context of preparedness and planning. The importance of partnerships between public health authorities at national and regional levels with labor migration networks to establish institutional and/or policy mechanisms are highlighted for ensuring effective preparedness and response planning. Strategies that can be taken by public health authorities working in both labor sending and labor receiving counties are also described.  The strategies described here may be useful for other labor sending country contexts in Asia with a high frequency and volume of migrant workers to and from the Gulf region.",2013 Jul 29,"['Wickramage, Kolitha', 'Peiris, Sharika', 'Agampodi, Suneth B']",F1000Res,,,True
86bd9005ed7a8aa7f895a9d0769b8dd8e4990e06,PMC,Cell Tropism Predicts Long-term Nucleotide Substitution Rates of Mammalian RNA Viruses,http://dx.doi.org/10.1371/journal.ppat.1003838,PMC3887100,24415935,CC BY,"The high rates of RNA virus evolution are generally attributed to replication with error-prone RNA-dependent RNA polymerases. However, these long-term nucleotide substitution rates span three orders of magnitude and do not correlate well with mutation rates or selection pressures. This substitution rate variation may be explained by differences in virus ecology or intrinsic genomic properties. We generated nucleotide substitution rate estimates for mammalian RNA viruses and compiled comparable published rates, yielding a dataset of 118 substitution rates of structural genes from 51 different species, as well as 40 rates of non-structural genes from 28 species. Through ANCOVA analyses, we evaluated the relationships between these rates and four ecological factors: target cell, transmission route, host range, infection duration; and three genomic properties: genome length, genome sense, genome segmentation. Of these seven factors, we found target cells to be the only significant predictors of viral substitution rates, with tropisms for epithelial cells or neurons (P<0.0001) as the most significant predictors. Further, one-tailed t-tests showed that viruses primarily infecting epithelial cells evolve significantly faster than neurotropic viruses (P<0.0001 and P<0.001 for the structural genes and non-structural genes, respectively). These results provide strong evidence that the fastest evolving mammalian RNA viruses infect cells with the highest turnover rates: the highly proliferative epithelial cells. Estimated viral generation times suggest that epithelial-infecting viruses replicate more quickly than viruses with different cell tropisms. Our results indicate that cell tropism is a key factor in viral evolvability.",2014 Jan 9,"['Hicks, Allison L.', 'Duffy, Siobain']",PLoS Pathog,,,True
cee3dd6c1927b863e94e9493295d99213401f158,PMC,Bat Airway Epithelial Cells: A Novel Tool for the Study of Zoonotic Viruses,http://dx.doi.org/10.1371/journal.pone.0084679,PMC3890267,24454736,CC BY,"Bats have been increasingly recognized as reservoir of important zoonotic viruses. However, until now many attempts to isolate bat-borne viruses in cell culture have been unsuccessful. Further, experimental studies on reservoir host species have been limited by the difficulty of rearing these species. The epithelium of the respiratory tract plays a central role during airborne transmission, as it is the first tissue encountered by viral particles. Although several cell lines from bats were established recently, no well-characterized, selectively cultured airway epithelial cells were available so far. Here, primary cells and immortalized cell lines from bats of the two important suborders Yangochiroptera and Yinpterochiroptera, Carollia perspicillata (Seba's short-tailed bat) and Eidolon helvum (Straw-colored fruit bat), were successfully cultured under standardized conditions from both fresh and frozen organ specimens by cell outgrowth of organ explants and by the use of serum-free primary cell culture medium. Cells were immortalized to generate permanent cell lines. Cells were characterized for their epithelial properties such as expression of cytokeratin and tight junctions proteins and permissiveness for viral infection with Rift-Valley fever virus and vesicular stomatitis virus Indiana. These cells can serve as suitable models for the study of bat-borne viruses and complement cell culture models for virus infection in human airway epithelial cells.",2014 Jan 13,"['Eckerle, Isabella', 'Ehlen, Lukas', 'Kallies, René', 'Wollny, Robert', 'Corman, Victor M.', 'Cottontail, Veronika M.', 'Tschapka, Marco', 'Oppong, Samuel', 'Drosten, Christian', 'Müller, Marcel A.']",PLoS One,,,True
eef61bdfa49b8652fd660b5b8b7e74cf51922505,PMC,Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China,http://dx.doi.org/10.1186/1471-2334-14-21,PMC3890533,24410932,CC BY,"BACKGROUND: This paper reports findings from the prevalence survey conducted in Shandong China in 2010, a province with a population of 94 million. This study aimed to estimate TB prevalence of the province in 2010 in comparison with the 2000 survey; and to compare yields of TB cases from different case finding approaches. METHODS: A population based, cross-sectional survey was conducted using multi-stage random cluster sampling. 54,279 adults participated in the survey with a response rate of 96%. Doctors interviewed and classified participants as suspected TB cases if they presented with persistent cough, abnormal chest X-ray (CXRAY), or both. Three sputum specimens of all suspected cases were collected and sent for smear microscopy and culture. RESULTS: Adjusted prevalence rate of bacteriologically confirmed cases was 34 per 100,000 for adults in Shandong in 2010. Compared to the 2000 survey, TB prevalence has declined by 80%. 53% of bacteriologically confirmed cases did not present persistent cough. The yield of bacteriologically confirmed cases was 47% by symptom screening and 95% by CXRAY. Over 50% of TB cases were among over 65’s. CONCLUSIONS: The prevalence rate of bacteriologically confirmed cases was significantly reduced compared with 2000. The survey raised challenges to identify TB cases without clear symptoms.",2014 Jan 11,"['Wei, Xiaolin', 'Zhang, Xiulei', 'Yin, Jia', 'Walley, John', 'Beanland, Rachel', 'Zou, Guanyang', 'Zhang, Hongmei', 'Li, Fang', 'Liu, Zhimin', 'Zee, Benny CY', 'Griffiths, Sian M']",BMC Infect Dis,,,True
8dab25c25f6598446d3b229d821402278b2bc0b9,PMC,Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling,http://dx.doi.org/10.1186/1471-2164-14-857,PMC3890716,24308360,CC BY,"BACKGROUD: Isatis indigotica is a widely used herb for the clinical treatment of colds, fever, and influenza in Traditional Chinese Medicine (TCM). Various structural classes of compounds have been identified as effective ingredients. However, little is known at genetics level about these active metabolites. In the present study, we performed de novo transcriptome sequencing for the first time to produce a comprehensive dataset of I. indigotica. RESULTS: A database of 36,367 unigenes (average length = 1,115.67 bases) was generated by performing transcriptome sequencing. Based on the gene annotation of the transcriptome, 104 unigenes were identified covering most of the catalytic steps in the general biosynthetic pathways of indole, terpenoid, and phenylpropanoid. Subsequently, the organ-specific expression patterns of the genes involved in these pathways, and their responses to methyl jasmonate (MeJA) induction, were investigated. Metabolites profile of effective phenylpropanoid showed accumulation pattern of secondary metabolites were mostly correlated with the transcription of their biosynthetic genes. According to the analysis of UDP-dependent glycosyltransferases (UGT) family, several flavonoids were indicated to exist in I. indigotica and further identified by metabolic profile using UPLC/Q-TOF. Moreover, applying transcriptome co-expression analysis, nine new, putative UGTs were suggested as flavonol glycosyltransferases and lignan glycosyltransferases. CONCLUSIONS: This database provides a pool of candidate genes involved in biosynthesis of effective metabolites in I. indigotica. Furthermore, the comprehensive analysis and characterization of the significant pathways are expected to give a better insight regarding the diversity of chemical composition, synthetic characteristics, and the regulatory mechanism which operate in this medical herb.",2013 Dec 5,"['Chen, Junfeng', 'Dong, Xin', 'Li, Qing', 'Zhou, Xun', 'Gao, Shouhong', 'Chen, Ruibing', 'Sun, Lianna', 'Zhang, Lei', 'Chen, Wansheng']",BMC Genomics,,,True
f5c1542555ee0f8e60c74414e328ed7845b932a4,PMC,Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling,http://dx.doi.org/10.1186/1471-2164-14-857,PMC3890716,24308360,CC BY,"BACKGROUD: Isatis indigotica is a widely used herb for the clinical treatment of colds, fever, and influenza in Traditional Chinese Medicine (TCM). Various structural classes of compounds have been identified as effective ingredients. However, little is known at genetics level about these active metabolites. In the present study, we performed de novo transcriptome sequencing for the first time to produce a comprehensive dataset of I. indigotica. RESULTS: A database of 36,367 unigenes (average length = 1,115.67 bases) was generated by performing transcriptome sequencing. Based on the gene annotation of the transcriptome, 104 unigenes were identified covering most of the catalytic steps in the general biosynthetic pathways of indole, terpenoid, and phenylpropanoid. Subsequently, the organ-specific expression patterns of the genes involved in these pathways, and their responses to methyl jasmonate (MeJA) induction, were investigated. Metabolites profile of effective phenylpropanoid showed accumulation pattern of secondary metabolites were mostly correlated with the transcription of their biosynthetic genes. According to the analysis of UDP-dependent glycosyltransferases (UGT) family, several flavonoids were indicated to exist in I. indigotica and further identified by metabolic profile using UPLC/Q-TOF. Moreover, applying transcriptome co-expression analysis, nine new, putative UGTs were suggested as flavonol glycosyltransferases and lignan glycosyltransferases. CONCLUSIONS: This database provides a pool of candidate genes involved in biosynthesis of effective metabolites in I. indigotica. Furthermore, the comprehensive analysis and characterization of the significant pathways are expected to give a better insight regarding the diversity of chemical composition, synthetic characteristics, and the regulatory mechanism which operate in this medical herb.",2013 Dec 5,"['Chen, Junfeng', 'Dong, Xin', 'Li, Qing', 'Zhou, Xun', 'Gao, Shouhong', 'Chen, Ruibing', 'Sun, Lianna', 'Zhang, Lei', 'Chen, Wansheng']",BMC Genomics,,,False
a3b45e62a604fc32b9f370e3e92bb3efc7f5c0b2,PMC,Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling,http://dx.doi.org/10.1186/1471-2164-14-857,PMC3890716,24308360,CC BY,"BACKGROUD: Isatis indigotica is a widely used herb for the clinical treatment of colds, fever, and influenza in Traditional Chinese Medicine (TCM). Various structural classes of compounds have been identified as effective ingredients. However, little is known at genetics level about these active metabolites. In the present study, we performed de novo transcriptome sequencing for the first time to produce a comprehensive dataset of I. indigotica. RESULTS: A database of 36,367 unigenes (average length = 1,115.67 bases) was generated by performing transcriptome sequencing. Based on the gene annotation of the transcriptome, 104 unigenes were identified covering most of the catalytic steps in the general biosynthetic pathways of indole, terpenoid, and phenylpropanoid. Subsequently, the organ-specific expression patterns of the genes involved in these pathways, and their responses to methyl jasmonate (MeJA) induction, were investigated. Metabolites profile of effective phenylpropanoid showed accumulation pattern of secondary metabolites were mostly correlated with the transcription of their biosynthetic genes. According to the analysis of UDP-dependent glycosyltransferases (UGT) family, several flavonoids were indicated to exist in I. indigotica and further identified by metabolic profile using UPLC/Q-TOF. Moreover, applying transcriptome co-expression analysis, nine new, putative UGTs were suggested as flavonol glycosyltransferases and lignan glycosyltransferases. CONCLUSIONS: This database provides a pool of candidate genes involved in biosynthesis of effective metabolites in I. indigotica. Furthermore, the comprehensive analysis and characterization of the significant pathways are expected to give a better insight regarding the diversity of chemical composition, synthetic characteristics, and the regulatory mechanism which operate in this medical herb.",2013 Dec 5,"['Chen, Junfeng', 'Dong, Xin', 'Li, Qing', 'Zhou, Xun', 'Gao, Shouhong', 'Chen, Ruibing', 'Sun, Lianna', 'Zhang, Lei', 'Chen, Wansheng']",BMC Genomics,,,False
023e329ab90febccbabdae8e920c2f1bf4c5419f,PMC,Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling,http://dx.doi.org/10.1186/1471-2164-14-857,PMC3890716,24308360,CC BY,"BACKGROUD: Isatis indigotica is a widely used herb for the clinical treatment of colds, fever, and influenza in Traditional Chinese Medicine (TCM). Various structural classes of compounds have been identified as effective ingredients. However, little is known at genetics level about these active metabolites. In the present study, we performed de novo transcriptome sequencing for the first time to produce a comprehensive dataset of I. indigotica. RESULTS: A database of 36,367 unigenes (average length = 1,115.67 bases) was generated by performing transcriptome sequencing. Based on the gene annotation of the transcriptome, 104 unigenes were identified covering most of the catalytic steps in the general biosynthetic pathways of indole, terpenoid, and phenylpropanoid. Subsequently, the organ-specific expression patterns of the genes involved in these pathways, and their responses to methyl jasmonate (MeJA) induction, were investigated. Metabolites profile of effective phenylpropanoid showed accumulation pattern of secondary metabolites were mostly correlated with the transcription of their biosynthetic genes. According to the analysis of UDP-dependent glycosyltransferases (UGT) family, several flavonoids were indicated to exist in I. indigotica and further identified by metabolic profile using UPLC/Q-TOF. Moreover, applying transcriptome co-expression analysis, nine new, putative UGTs were suggested as flavonol glycosyltransferases and lignan glycosyltransferases. CONCLUSIONS: This database provides a pool of candidate genes involved in biosynthesis of effective metabolites in I. indigotica. Furthermore, the comprehensive analysis and characterization of the significant pathways are expected to give a better insight regarding the diversity of chemical composition, synthetic characteristics, and the regulatory mechanism which operate in this medical herb.",2013 Dec 5,"['Chen, Junfeng', 'Dong, Xin', 'Li, Qing', 'Zhou, Xun', 'Gao, Shouhong', 'Chen, Ruibing', 'Sun, Lianna', 'Zhang, Lei', 'Chen, Wansheng']",BMC Genomics,,,False
8ea9dbee38148772a4a9701d38358512c3d31a47,PMC,Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling,http://dx.doi.org/10.1186/1471-2164-14-857,PMC3890716,24308360,CC BY,"BACKGROUD: Isatis indigotica is a widely used herb for the clinical treatment of colds, fever, and influenza in Traditional Chinese Medicine (TCM). Various structural classes of compounds have been identified as effective ingredients. However, little is known at genetics level about these active metabolites. In the present study, we performed de novo transcriptome sequencing for the first time to produce a comprehensive dataset of I. indigotica. RESULTS: A database of 36,367 unigenes (average length = 1,115.67 bases) was generated by performing transcriptome sequencing. Based on the gene annotation of the transcriptome, 104 unigenes were identified covering most of the catalytic steps in the general biosynthetic pathways of indole, terpenoid, and phenylpropanoid. Subsequently, the organ-specific expression patterns of the genes involved in these pathways, and their responses to methyl jasmonate (MeJA) induction, were investigated. Metabolites profile of effective phenylpropanoid showed accumulation pattern of secondary metabolites were mostly correlated with the transcription of their biosynthetic genes. According to the analysis of UDP-dependent glycosyltransferases (UGT) family, several flavonoids were indicated to exist in I. indigotica and further identified by metabolic profile using UPLC/Q-TOF. Moreover, applying transcriptome co-expression analysis, nine new, putative UGTs were suggested as flavonol glycosyltransferases and lignan glycosyltransferases. CONCLUSIONS: This database provides a pool of candidate genes involved in biosynthesis of effective metabolites in I. indigotica. Furthermore, the comprehensive analysis and characterization of the significant pathways are expected to give a better insight regarding the diversity of chemical composition, synthetic characteristics, and the regulatory mechanism which operate in this medical herb.",2013 Dec 5,"['Chen, Junfeng', 'Dong, Xin', 'Li, Qing', 'Zhou, Xun', 'Gao, Shouhong', 'Chen, Ruibing', 'Sun, Lianna', 'Zhang, Lei', 'Chen, Wansheng']",BMC Genomics,,,False
f7f54aa815c6e0608b2e0ebe3499603926135463,PMC,Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling,http://dx.doi.org/10.1186/1471-2164-14-857,PMC3890716,24308360,CC BY,"BACKGROUD: Isatis indigotica is a widely used herb for the clinical treatment of colds, fever, and influenza in Traditional Chinese Medicine (TCM). Various structural classes of compounds have been identified as effective ingredients. However, little is known at genetics level about these active metabolites. In the present study, we performed de novo transcriptome sequencing for the first time to produce a comprehensive dataset of I. indigotica. RESULTS: A database of 36,367 unigenes (average length = 1,115.67 bases) was generated by performing transcriptome sequencing. Based on the gene annotation of the transcriptome, 104 unigenes were identified covering most of the catalytic steps in the general biosynthetic pathways of indole, terpenoid, and phenylpropanoid. Subsequently, the organ-specific expression patterns of the genes involved in these pathways, and their responses to methyl jasmonate (MeJA) induction, were investigated. Metabolites profile of effective phenylpropanoid showed accumulation pattern of secondary metabolites were mostly correlated with the transcription of their biosynthetic genes. According to the analysis of UDP-dependent glycosyltransferases (UGT) family, several flavonoids were indicated to exist in I. indigotica and further identified by metabolic profile using UPLC/Q-TOF. Moreover, applying transcriptome co-expression analysis, nine new, putative UGTs were suggested as flavonol glycosyltransferases and lignan glycosyltransferases. CONCLUSIONS: This database provides a pool of candidate genes involved in biosynthesis of effective metabolites in I. indigotica. Furthermore, the comprehensive analysis and characterization of the significant pathways are expected to give a better insight regarding the diversity of chemical composition, synthetic characteristics, and the regulatory mechanism which operate in this medical herb.",2013 Dec 5,"['Chen, Junfeng', 'Dong, Xin', 'Li, Qing', 'Zhou, Xun', 'Gao, Shouhong', 'Chen, Ruibing', 'Sun, Lianna', 'Zhang, Lei', 'Chen, Wansheng']",BMC Genomics,,,False
217114455f564a37a057840d761b901fd372bef3,PMC,Molecular Detection of Porcine Torovirus in Piglets with Diarrhea in Southwest China,http://dx.doi.org/10.1155/2013/984282,PMC3891532,24459455,CC BY,"Porcine torovirus (PToV) was detected from intestinal samples of piglets with diarrhea from 20 farms in southwest China. The total prevalence of PToV was 45% (9 out of 20 farms); it was the first detection of PToV in China, and also the study analyzed the phylogenetic relationships between the Chinese PToV and PToV reference strains as well as other representative toroviruses. Genetic and phylogenetic analysis showed the existence of genetic diversity among geographically separated PToV. Statistical analysis of the PToV positive rate as well as a survey for other enteric pathogens in diarrheic pigs suggests that PToV may play a role as a causative agent of severe diarrhea in piglets.",2013 Dec 26,"['Zhou, Yuancheng', 'Chen, Lei', 'Zhu, Ling', 'Xu, Zhiwen']",ScientificWorldJournal,,,True
ab906d73fa3fecf440ed8c98ad852397bf7bee1f,PMC,SIRT1 Activating compounds reduce oxidative stress mediated neuronal loss in viral induced CNS demyelinating disease,http://dx.doi.org/10.1186/2051-5960-2-3,PMC3892130,24383546,CC BY,"BACKGROUND: Multiple sclerosis (MS) is characterized by central nervous system inflammation and demyelination, and increasing evidence demonstrates significant neuronal damage also occurs and is associated with permanent functional impairment. Current MS therapies have limited ability to prevent neuronal damage, suggesting additional neuroprotective therapies are needed. Compounds that activate the NAD(+)-dependent SIRT1 deacetylase prevent neuronal loss in an autoimmune-mediated MS model, but the mechanism of this effect is unknown, and it is unclear whether SIRT1 activating compounds exert similar effects in demyelinating disease induced by other etiologies. We measured neuronal loss in C57BL/6 mice inoculated with a neurotropic strain of mouse hepatitis virus, MHV-A59, that induces an MS-like disease. RESULTS: Oral treatment with the SIRT1 activating compound SRTAW04 significantly increased SIRT1 activity within optic nerves and prevented neuronal loss during optic neuritis, an inflammatory demyelinating optic nerve lesion that occurs in MS and its animal models. MHV-A59 induced neuronal loss was associated with reactive oxygen species (ROS) accumulation, and SRTAW04 treatment significantly reduced ROS levels while promoting increased expression of enzymes involved in mitochondrial function and reduction of ROS. SRTAW04 exerted similar protective effects in EAE spinal cords, with decreased demyelination. CONCLUSIONS: Results demonstrate that SIRT1 activating compounds prevent neuronal loss in viral-induced demyelinating disease similar to their effects in autoimmune-mediated disease. One mechanism of this neuroprotective effect involves increasing mitochondrial biogenesis with reduction of oxidative stress. SIRT1 activators represent a potential neuroprotective therapy for MS. Understanding common mechanisms of these effects in distinct disease models will help identify targets for more specific therapies.",2014 Jan 2,"['Khan, Reas S', 'Dine, Kimberly', 'Das Sarma, Jayasri', 'Shindler, Kenneth S']",Acta Neuropathol Commun,,,True
30556242d064131f0f2b645a727d42c55dc1c71e,PMC,"Isolation, Characterization, and Molecular Modeling of a Rheumatoid Factor from a Hepatitis C Virus Infected Patient with Sjögren's Syndrome",http://dx.doi.org/10.1155/2013/516516,PMC3892945,24489505,CC BY,"We have previously isolated several IgG rheumatoid factors (RFs) from patients with both rheumatoid arthritis and idiopathic thrombocytopenia purpura using phage display system. To study IgG RFs in patients with other autoimmune diseases, phage display antibody libraries from a hepatitis C virus infected patient with Sjögren's syndrome were constructed. After panning, a specific clone RFL11 was isolated for characterization in advance. The binding activity and specificity of RFL11 to IgG Fc fragment were comparable to those of RFs previously isolated. The analysis with existed RF-Fc complex structures indicated the homology model of RFL11 is similar to IgM RF61 complex with high binding affinity of about 6 × 10(−8) M. This effect resulted from longer complementarity-determining region (CDR) combining key somatic mutations. In the RFL11-Fc interfaces, the CDR-H3 loop forms a finger-like structure extending into the bottom of Fc pocket and resulting in strong ion and cation-pi interactions. Moreover, a process of antigen-driven maturation was proven by somatically mutated VH residues on H2 and H3 CDR loops in the interfaces. Taken together, these results suggested that high affinity IgG RFs can be generated in patients with Sjögren's syndrome and may play an important role in the pathogenesis of this autoimmune disease.",2013 Dec 30,"['Lee, Yu-Ching', 'Tsai, Keng-Chang', 'Leu, Sy-Jye', 'Wang, Tuan-Jen', 'Liu, Chia-Yu', 'Yang, Yi-Yuan']",ScientificWorldJournal,,,True
8ecb2c48d129fe9df101cb136f9496000d4bb581,PMC,Characterization of Angiotensin-Converting Enzyme 2 Ectodomain Shedding from Mouse Proximal Tubular Cells,http://dx.doi.org/10.1371/journal.pone.0085958,PMC3893316,24454948,CC BY,"Angiotensin-converting enzyme 2 (ACE2) is highly expressed in the kidney proximal tubule, where it cleaves angiotensin (Ang) II to Ang-(1-7). Urinary ACE2 levels increase in diabetes, suggesting that ACE2 may be shed from tubular cells. The aim of this study was to determine if ACE2 is shed from proximal tubular cells, to characterize ACE2 fragments, and to study pathways for shedding. Studies involved primary cultures of mouse proximal tubular cells, with ACE2 activity measured using a synthetic substrate, and analysis of ACE2 fragments by immunoblots and mass spectrometry. The culture media from mouse proximal tubular cells demonstrated a time-dependent increase in ACE2 activity, suggesting constitutive ACE2 shedding. ACE2 was detected in media as two bands at ∼90 kDa and ∼70 kDa on immunoblots. By contrast, full-length ACE2 appeared at ∼100 kDa in cell lysates or mouse kidney cortex. Mass spectrometry of the two deglycosylated fragments identified peptides matching mouse ACE2 at positions 18-706 and 18-577, respectively. The C-terminus of the 18-706 peptide fragment contained a non-tryptic site, suggesting that Met(706) is a candidate ACE2 cleavage site. Incubation of cells in high D-glucose (25 mM) (and to a lesser extent Ang II) for 48–72 h increased ACE2 activity in the media (p<0.001), an effect blocked by inhibition of a disintegrin and metalloproteinase (ADAM)17. High D-glucose increased ADAM17 activity in cell lysates (p<0.05). These data indicate that two glycosylated ACE2 fragments are constitutively shed from mouse proximal tubular cells. ACE2 shedding is stimulated by high D-glucose, at least partly via an ADAM17-mediated pathway. The results suggest that proximal tubular shedding of ACE2 may increase in diabetes, which could enhance degradation of Ang II in the tubular lumen, and increase levels of Ang-(1-7).",2014 Jan 15,"['Xiao, Fengxia', 'Zimpelmann, Joseph', 'Agaybi, Samih', 'Gurley, Susan B.', 'Puente, Lawrence', 'Burns, Kevin D.']",PLoS One,,,True
997ebf63461efa3e7cb1fc3014fc957659705202,PMC,Measuring psychological resilience to disasters: are evidence-based indicators an achievable goal?,http://dx.doi.org/10.1186/1476-069X-12-115,PMC3893382,24359448,CC BY,"Despite rising interest on the concept of societal resilience and its measurement, little has been done to provide operational indicators. Importantly, an evidence-based approach to assess the suitability of indicators remains unexplored. Furthermore few approaches that exist do not investigate indicators of psychological resilience, which is emerging as an important component of societal resilience to disasters. Disasters are events which overwhelm local capacities, often producing human losses, injury and damage to the affected communities. As climate hazards and disasters are likely to increase in the coming decades, strengthening the capacity of societies to withstand these shocks and recover quickly is vital. In this review, we search the Web of Knowledge to summarize the evidence on indicators of psychological resilience to disasters and provided a qualitative assessment of six selected studies. We find that an evidence-based approach using features from systematic reviews is useful to compile, select and assess the evidence and elucidate robust indicators. We conclude that strong social support received after a disaster is associated with an increased psychological resilience whereas a female gender is connected with a decrease in the likelihood of a resilient outcome. These results are consistent across disaster settings and cultures and are representative of approximately 13 million disaster-exposed civilians of adult age. An approach such as this that collects and evaluates evidence will allow indicators of resilience to be much more revealing and useful in the future. They will provide a robust basis to prioritize indicators to act upon through intersectoral policies and post-disaster public health interventions.",2013 Dec 20,"['Rodriguez-Llanes, Jose Manuel', 'Vos, Femke', 'Guha-Sapir, Debarati']",Environ Health,,,True
a648c37b99ce3b55b5a07125c086a958bbbf3c13,PMC,A bio-objects approach to biosecurity: the “mutant flu” controversy as a bio-objectification process,http://dx.doi.org/10.3325/cmj.2013.54.592,PMC3893992,24382857,CC BY,,2013 Dec,"Cañada, Jose A.",Croat Med J,,,True
16c14c63746634d9cc1a2d4257b7d7560af187ba,PMC,Alphavirus Mutator Variants Present Host-Specific Defects and Attenuation in Mammalian and Insect Models,http://dx.doi.org/10.1371/journal.ppat.1003877,PMC3894214,24453971,CC BY,"Arboviruses cycle through both vertebrates and invertebrates, which requires them to adapt to disparate hosts while maintaining genetic integrity during genome replication. To study the genetic mechanisms and determinants of these processes, we use chikungunya virus (CHIKV), a re-emerging human pathogen transmitted by the Aedes mosquito. We previously isolated a high fidelity (or antimutator) polymerase variant, C483Y, which had decreased fitness in both mammalian and mosquito hosts, suggesting this residue may be a key molecular determinant. To further investigate effects of position 483 on RNA-dependent RNA-polymerase (RdRp) fidelity, we substituted every amino acid at this position. We isolated novel mutators with decreased replication fidelity and higher mutation frequencies, allowing us to examine the fitness of error-prone arbovirus variants. Although CHIKV mutators displayed no major replication defects in mammalian cell culture, they had reduced specific infectivity and were attenuated in vivo. Unexpectedly, mutator phenotypes were suppressed in mosquito cells and the variants exhibited significant defects in RNA synthesis. Consequently, these replication defects resulted in strong selection for reversion during infection of mosquitoes. Since residue 483 is conserved among alphaviruses, we examined the analogous mutations in Sindbis virus (SINV), which also reduced polymerase fidelity and generated replication defects in mosquito cells. However, replication defects were mosquito cell-specific and were not observed in Drosophila S2 cells, allowing us to evaluate the potential attenuation of mutators in insect models where pressure for reversion was absent. Indeed, the SINV mutator variant was attenuated in fruit flies. These findings confirm that residue 483 is a determinant regulating alphavirus polymerase fidelity and demonstrate proof of principle that arboviruses can be attenuated in mammalian and insect hosts by reducing fidelity.",2014 Jan 16,"['Rozen-Gagnon, Kathryn', 'Stapleford, Kenneth A.', 'Mongelli, Vanesa', 'Blanc, Hervé', 'Failloux, Anna-Bella', 'Saleh, Maria-Carla', 'Vignuzzi, Marco']",PLoS Pathog,,,True
a2d455f2d873e1be7f2db4b069b6e40f3faf168b,PMC,Gammaherpesviral Gene Expression and Virion Composition Are Broadly Controlled by Accelerated mRNA Degradation,http://dx.doi.org/10.1371/journal.ppat.1003882,PMC3894220,24453974,CC BY,"Lytic gammaherpesvirus infection restricts host gene expression by promoting widespread degradation of cytoplasmic mRNA through the activity of the viral endonuclease SOX. Though generally assumed to be selective for cellular transcripts, the extent to which SOX impacts viral mRNA stability has remained unknown. We addressed this issue using the model murine gammaherpesvirus MHV68 and, unexpectedly, found that all stages of viral gene expression are controlled through mRNA degradation. Using both comprehensive RNA expression profiling and half-life studies we reveal that the levels of the majority of viral mRNAs but not noncoding RNAs are tempered by MHV68 SOX (muSOX) activity. The targeting of viral mRNA by muSOX is functionally significant, as it impacts intracellular viral protein abundance and progeny virion composition. In the absence of muSOX-imposed gene expression control the viral particles display increased cell surface binding and entry as well as enhanced immediate early gene expression. These phenotypes culminate in a viral replication defect in multiple cell types as well as in vivo, highlighting the importance of maintaining the appropriate balance of viral RNA during gammaherpesviral infection. This is the first example of a virus that fails to broadly discriminate between cellular and viral transcripts during host shutoff and instead uses the targeting of viral messages to fine-tune overall gene expression.",2014 Jan 16,"['Abernathy, Emma', 'Clyde, Karen', 'Yeasmin, Rukhsana', 'Krug, Laurie T.', 'Burlingame, Al', 'Coscoy, Laurent', 'Glaunsinger, Britt']",PLoS Pathog,,,True
89a3606a8ebb09ebab239030d3ef7082c74b884b,PMC,Gammaherpesviral Gene Expression and Virion Composition Are Broadly Controlled by Accelerated mRNA Degradation,http://dx.doi.org/10.1371/journal.ppat.1003882,PMC3894220,24453974,CC BY,"Lytic gammaherpesvirus infection restricts host gene expression by promoting widespread degradation of cytoplasmic mRNA through the activity of the viral endonuclease SOX. Though generally assumed to be selective for cellular transcripts, the extent to which SOX impacts viral mRNA stability has remained unknown. We addressed this issue using the model murine gammaherpesvirus MHV68 and, unexpectedly, found that all stages of viral gene expression are controlled through mRNA degradation. Using both comprehensive RNA expression profiling and half-life studies we reveal that the levels of the majority of viral mRNAs but not noncoding RNAs are tempered by MHV68 SOX (muSOX) activity. The targeting of viral mRNA by muSOX is functionally significant, as it impacts intracellular viral protein abundance and progeny virion composition. In the absence of muSOX-imposed gene expression control the viral particles display increased cell surface binding and entry as well as enhanced immediate early gene expression. These phenotypes culminate in a viral replication defect in multiple cell types as well as in vivo, highlighting the importance of maintaining the appropriate balance of viral RNA during gammaherpesviral infection. This is the first example of a virus that fails to broadly discriminate between cellular and viral transcripts during host shutoff and instead uses the targeting of viral messages to fine-tune overall gene expression.",2014 Jan 16,"['Abernathy, Emma', 'Clyde, Karen', 'Yeasmin, Rukhsana', 'Krug, Laurie T.', 'Burlingame, Al', 'Coscoy, Laurent', 'Glaunsinger, Britt']",PLoS Pathog,,,False
8806d2b5dd6c0709ed0fc8e99153cbef69fd4614,PMC,Occurrence and phylogenetic analysis of bovine respiratory syncytial virus in outbreaks of respiratory disease in Norway,http://dx.doi.org/10.1186/1746-6148-10-15,PMC3896707,24423030,CC BY,"BACKGROUND: Bovine respiratory syncytial virus (BRSV) is one of the major pathogens involved in the bovine respiratory disease (BRD) complex. The seroprevalence to BRSV in Norwegian cattle herds is high, but its role in epidemics of respiratory disease is unclear. The aims of the study were to investigate the etiological role of BRSV and other respiratory viruses in epidemics of BRD and to perform phylogenetic analysis of Norwegian BRSV strains. RESULTS: BRSV infection was detected either serologically and/or virologically in 18 (86%) of 21 outbreaks and in most cases as a single viral agent. When serology indicated that bovine coronavirus and/or bovine parainfluenza virus 3 were present, the number of BRSV positive animals in the herd was always higher, supporting the view of BRSV as the main pathogen. Sequencing of the G gene of BRSV positive samples showed that the current circulating Norwegian BRSVs belong to genetic subgroup II, along with other North European isolates. One isolate from an outbreak in Norway in 1976 was also investigated. This strain formed a separate branch in subgroup II, clearly different from the current Scandinavian sequences. The currently circulating BRSV could be divided into two different strains that were present in the same geographical area at the same time. The sequence variations between the two strains were in an antigenic important part of the G protein. CONCLUSION: The results demonstrated that BRSV is the most important etiological agent of epidemics of BRD in Norway and that it often acts as the only viral agent. The phylogenetic analysis of the Norwegian strains of BRSV and several previously published isolates supported the theory of geographical and temporal clustering of BRSV.",2014 Jan 14,"['Klem, Thea B', 'Rimstad, Espen', 'Stokstad, Maria']",BMC Vet Res,,,True
b54ab920006bd7dceb8851d37e0eef82d3711534,PMC,Presence of infectious agents and co-infections in diarrheic dogs determined with a real-time polymerase chain reaction-based panel,http://dx.doi.org/10.1186/1746-6148-10-23,PMC3896730,24433321,CC BY,"BACKGROUND: Infectious diarrhea can be caused by bacteria, viruses, or protozoan organisms, or a combination of these. The identification of co-infections in dogs is important to determine the prognosis and to plan strategies for their treatment and prophylaxis. Although many pathogens have been individually detected with real-time polymerase chain reaction (PCR), a comprehensive panel of agents that cause diarrhea in privately owned dogs has not yet been established. The objective of this study was to use a real-time PCR diarrhea panel to survey the frequencies of pathogens and co-infections in owned dogs attended in a veterinary hospital with and without diarrhea, as well the frequency in different countries. Feces samples were tested for canine distemper virus, canine coronavirus, canine parvovirus type 2 (CPV-2), Clostridium perfringens alpha toxin (CPA), Cryptosporidium spp., Giardia spp., and Salmonella spp. using molecular techniques. RESULTS: In total, 104 diarrheic and 43 control dogs that were presented consecutively at a major private veterinary hospital were included in the study. Overall, 71/104 (68.3%) dogs with diarrhea were positive for at least one pathogen: a single infection in 39/71 dogs (54.9%) and co-infections in 32/71 dogs (45.1%), including 21/32 dogs (65.6%) with dual, 5/32 (15.6%) with triple, and 6/32 (18.8%) with quadruple infections. In the control group, 13/43 (30.2%) dogs were positive, all with single infections only. The most prevalent pathogens in the diarrheic dogs were CPA (40/104 dogs, 38.5%), CPV-2 (36/104 dogs, 34.6%), and Giardia spp. (14/104 dogs, 13.5%). CPV-2 was the most prevalent pathogen in the dual co-infections, associated with CPA, Cryptosporidium spp., or Giardia spp. No statistical difference (P = 0.8374) was observed in the duration of diarrhea or the number of deaths (P = 0.5722) in the presence or absence of single or co-infections. CONCLUSIONS: Diarrheic dogs showed a higher prevalence of pathogen infections than the controls. Whereas the healthy dogs had only single infections, about half the diarrheic dogs had co-infections. Therefore, multiple pathogens should be investigated in dogs presenting with diarrhea. The effects of multiple pathogens on the disease outcomes remain unclear because the rate of death and the duration of diarrhea did not seem to be affected by these factors.",2014 Jan 16,"['Gizzi, Aline Baumann da Rocha', 'Oliveira, Simone Tostes', 'Leutenegger, Christian M', 'Estrada, Marko', 'Kozemjakin, Denise Adamczyk', 'Stedile, Rafael', 'Marcondes, Mary', 'Biondo, Alexander Welker']",BMC Vet Res,,,True
304d61d063b602c2971b9df3ce167445c9880645,PMC,A SYBR Green I based real time RT-PCR assay for specific detection and quantitation of Peste des petits ruminants virus,http://dx.doi.org/10.1186/1746-6148-10-22,PMC3896792,24423231,CC BY,"BACKGROUND: Peste des petits ruminants (PPR) is an economically important disease of small ruminants such as sheep and goats. The disease is characterized by severe pyrexia, oculo-nasal discharge, pneumonia, necrosis and ulceration of the mucous membrane and inflammation of the gastro-intestinal tract leading to severe diarrhea. A SYBR Green I based real time RT-PCR targeting the N gene of PPRV has not been established for PPRV detection. Thus, the objective of present study was to develop highly sensitive N gene target SYBR Green I real time RT-PCR for specific detection and quantification of PPRV in clinical samples. A set of primers was designed to detect the nucleocapsid (N) gene of PPRV. RESULTS: The assay exhibited high specificity as all the viruses which have clinical and structural similarities to PPRV including Canine distemper virus (CDV), Measles virus (MV), Bluetongue virus (BTV) and Newcastle disease virus (NDV) failed to show an amplification signal. The lower detection limit of the assay was 5.11 copies/μl (Ct value of 33.67 ± 0.5) and 0.001 TCID(50)/ml (Ct value of 34.7 ± 0.5) based on plasmid copy number and tissue culture infectivity titre. The assay was 3-log more sensitive than the conventional RT-PCR. The coefficient of variation (CV) values for intra- and inter-assay variability were low, ranging from 0.32% - 2.31%, and 0.71% - 5.32%, respectively. To evaluate the performance of the newly developed assay, a total of 36 clinical samples suspected of PPR were screened for the presence of PPRV in parallel with conventional RT-PCR. The real time RT-PCR assay detected PPRV in 30 (83.3%) of clinical samples compared to 16 (44.4%) by conventional RT-PCR. CONCLUSIONS: The two-step SYBR Green I based real time RT-PCR assay reported here is highly sensitive, specific, reproducible and rapid for detection and quantification of PPRV nucleic acids.",2014 Jan 14,"['Abera, Tsegalem', 'Thangavelu, Ardhanary', 'Joy Chandran, Navamani Daniel', 'Raja, Angamuthu']",BMC Vet Res,,,True
09db5b9c6d7c4f5d804c532939fb4f824c409bb6,PMC,Enteropathogen co-infection in UK cats with diarrhoea,http://dx.doi.org/10.1186/1746-6148-10-13,PMC3896830,24410914,CC BY,"BACKGROUND: Individual enteropathogen infections in healthy and clinically ill cats are well described, but prevalence and patterns of enteropathogen co-infection have only been reported on a limited basis. We studied enteropathogen co-infection in diarrhoeic UK cats using results of a real time PCR assay for 8 enteropathogenic species; feline coronavirus (Co), feline panleukopenia virus (Pa), Clostridium perfringens (Cl), Salmonella enterica (Sa), Giardia spp. (Gi), Tritrichomonas foetus (Tr), Cryptosporidium spp. (Cr), and Toxoplasma gondii (To). Age, gender, breed and history were recorded. PCR panels from 1088 diarrhoeic cats were available for analysis. RESULTS: Overall enteropathogen prevalence was 56.9% (Co), 22.1% (Pa), 56.6% (Cl), 0.8% (Sa), 20.6% (Gi), 18.8% (Tr), 24.4% (Cr) and 1.0% (To). Prevalence of Co, Gi and Tr was higher in pedigree cats compared to non-pedigree cats (DSH) and prevalence decreased with increasing age for Co, Pa, Gi, Cr and Tr. Co-infection was common: ≥2 enteropathogens were detected in 62.5% of cats, and 13.3% of cats had ≥4 enteropathogens. Mean ( [Formula: see text]) enteropathogen co-infection 2.01 (±1.3 SD), was significantly higher in pedigree cats ( [Formula: see text] =2.51) compared to DSH ( [Formula: see text] =1.68) and decreased with age ( [Formula: see text] =2.64 <6 months, [Formula: see text] =1.68 for >1 yr). More cats were negative for all 8 enteropathogens tested (12.7%) than expected. When exact combinations of co-infection were examined, Tr tended to be found in combinations with Co, Cl, and Gi. CONCLUSIONS: Multiple infections should be considered the most likely result of faecal testing in cats, and case management needs to take this into account. In contrast, the relatively high percentage of cats negative for all 8 enteropathogens tested could indicate an innate resistance to infection. Alternatively it could indicate a lack of exposure to these 8 enteropathogens or the presence of other enteropathogens not assessed by this assay.",2014 Jan 12,"['Paris, Jasmin K', 'Wills, Sheila', 'Balzer, Hans-Jörg', 'Shaw, Darren J', 'Gunn-Moore, Danièlle A']",BMC Vet Res,,,True
5bc5b2f9dee2ff454efe226384070d467112e25d,PMC,A 2D graphical representation of the sequences of DNA based on triplets and its application,http://dx.doi.org/10.1186/1687-4153-2014-1,PMC3896961,24383852,CC BY,"In this paper, we first present a new concept of ‘weight’ for 64 triplets and define a different weight for each kind of triplet. Then, we give a novel 2D graphical representation for DNA sequences, which can transform a DNA sequence into a plot set to facilitate quantitative comparisons of DNA sequences. Thereafter, associating with a newly designed measure of similarity, we introduce a novel approach to make similarities/dissimilarities analysis of DNA sequences. Finally, the applications in similarities/dissimilarities analysis of the complete coding sequences of β-globin genes of 11 species illustrate the utilities of our newly proposed method.",2014 Jan 2,"['Zou, Sai', 'Wang, Lei', 'Wang, Junfeng']",EURASIP J Bioinform Syst Biol,,,True
639215bc06ff8518135073d907b7bf6a9089c1fc,PMC,AAV Vectors Vaccines Against Infectious Diseases,http://dx.doi.org/10.3389/fimmu.2014.00005,PMC3896988,24478774,CC BY,"Since their discovery as a tool for gene transfer, vectors derived from the adeno-associated virus (AAV) have been used for gene therapy applications and attracted scientist to this field for their exceptional properties of efficiency of in vivo gene transfer and the level and duration of transgene expression. For many years, AAVs have been considered as low immunogenic vectors due to their ability to induce long-term expression of non-self-proteins in contrast to what has been observed with other viral vectors, such as adenovirus, for which strong immune responses against the same transgene products were documented. The perceived low immunogenicity likely explains why the use of AAV vectors for vaccination was not seriously considered before the early 2000s. Indeed, while analyses conducted using a variety of transgenes and animal species slowly changed the vision of immunological properties of AAVs, an increasing number of studies were also performed in the field of vaccination. Even if the comparison with other modes of vaccination was not systemically performed, the analyses conducted so far in the field of active immunotherapy strongly suggest that AAVs possess some interesting features to be used as tools to produce an efficient and sustained antibody response. In addition, recent studies also highlighted the potential of AAVs for passive immunotherapy. This review summarizes the main studies conducted to evaluate the potential of AAV vectors for vaccination against infectious agents and discusses their advantages and drawbacks. Altogether, the variety of studies conducted in this field contributes to the understanding of the immunological properties of this versatile virus and to the definition of its possible future applications.",2014 Jan 21,"['Nieto, Karen', 'Salvetti, Anna']",Front Immunol,,,True
d17ba127439d63e04c399c19a06fa63998d65e6d,PMC,Immunosuppressive Drugs Modulate the Replication of Hepatitis B Virus (HBV) in a Hydrodynamic Injection Mouse Model,http://dx.doi.org/10.1371/journal.pone.0085832,PMC3897536,24465734,CC BY,"Hepatitis B virus (HBV) reactivation and recurrence are common in patients under immunosuppression and can be controlled by hepatitis B immunoglobulin, antivirals, and hepatitis B vaccine. However, the detailed analysis of HBV infection under immunosuppression is essential for the prophylaxis and therapy for HBV reactivation and recurrence. In this study, HBV replication and T cell responses were analyzed in a HBV-transfected mouse model under immunosuppressive therapy. During the treatment, HBV replication was at a high level in mice treated with dexamethasone, cyclosporine, and cyclophosphamide, whereas was terminated in mice treated with mycophenolate mofetil. After the withdrawal, HBV replication was at low or high levels in the dexamethasone-treated mice or in both cyclosporine- and cyclophosphamide-treated mice. The early withdrawal of cyclosporine allowed the recovery of suppressed T cell responses and led to subsequent HBV clearance, while the adoptive immune transfer to the mice with HBV persistence led to HBV suppression. Taken together, long-term HBV persistence under immunosuppression depends on the immunosuppressive drugs used and on the treatment duration and is mediated by the suppressed intrahepatic CD8 T cell response. These data may be helpful for individualized immunosuppressive therapy in patients with high risk of HBV reactivation and recurrence, and the mouse system is suitable for studying HBV reactivation and recurrence under immunosuppression.",2014 Jan 21,"['Wang, Junzhong', 'Wang, Baoju', 'Huang, Shunmei', 'Song, Zhitao', 'Wu, Jun', 'Zhang, Ejuan', 'Zhu, Zhenni', 'Zhu, Bin', 'Yin, Ying', 'Lin, Yong', 'Xu, Yang', 'Zheng, Xin', 'Lu, Mengji', 'Yang, Dongliang']",PLoS One,,,True
da412bad3772b82d1b3ab2d1aa1e00035869ac55,PMC,"Nasal swab samples and real-time polymerase chain reaction assays in community-based, longitudinal studies of respiratory viruses: the importance of sample integrity and quality control",http://dx.doi.org/10.1186/1471-2334-14-15,PMC3897990,24405747,CC BY,"BACKGROUND: Carefully conducted, community-based, longitudinal studies are required to gain further understanding of the nature and timing of respiratory viruses causing infections in the population. However, such studies pose unique challenges for field specimen collection, including as we have observed the appearance of mould in some nasal swab specimens. We therefore investigated the impact of sample collection quality and the presence of visible mould in samples upon respiratory virus detection by real-time polymerase chain reaction (PCR) assays. METHODS: Anterior nasal swab samples were collected from infants participating in an ongoing community-based, longitudinal, dynamic birth cohort study. The samples were first collected from each infant shortly after birth and weekly thereafter. They were then mailed to the laboratory where they were catalogued, stored at -80°C and later screened by PCR for 17 respiratory viruses. The quality of specimen collection was assessed by screening for human deoxyribonucleic acid (DNA) using endogenous retrovirus 3 (ERV3). The impact of ERV3 load upon respiratory virus detection and the impact of visible mould observed in a subset of swabs reaching the laboratory upon both ERV3 loads and respiratory virus detection was determined. RESULTS: In total, 4933 nasal swabs were received in the laboratory. ERV3 load in nasal swabs was associated with respiratory virus detection. Reduced respiratory virus detection (odds ratio 0.35; 95% confidence interval 0.27-0.44) was observed in samples where the ERV3 could not be identified. Mould was associated with increased time of samples reaching the laboratory and reduced ERV3 loads and respiratory virus detection. CONCLUSION: Suboptimal sample collection and high levels of visible mould can impact negatively upon sample quality. Quality control measures, including monitoring human DNA loads using ERV3 as a marker for epithelial cell components in samples should be undertaken to optimize the validity of real-time PCR results for respiratory virus investigations in community-based studies.",2014 Jan 9,"['Alsaleh, Asma N', 'Whiley, David M', 'Bialasiewicz, Seweryn', 'Lambert, Stephen B', 'Ware, Robert S', 'Nissen, Michael D', 'Sloots, Theo P', 'Grimwood, Keith']",BMC Infect Dis,,,True
eae06fd0ce129fbfb73f70fd0c49df18c40632dd,PMC,Thank you to Virology Journal's peer reviewers in 2013,http://dx.doi.org/10.1186/1743-422X-11-4,PMC3898089,,CC BY,"The editors of Virology Journal would like to thank all our reviewers who have contributed to the journal in Volume 10 (2013). The success of any scientific journal depends on an effective and strict peer review process and Virology Journal could not operate without your contribution. We are grateful to the large number of reviewers (1026 to be exact!), who have done a great job in not only lifting the quality of the journal’s scientific peer reviewing process, but also helped us to achieve our goal of a median time to first decision of just 35 days. Our record time from submission to online, open access, publication in 2013 was 22 days for a Research Article [1] and 28 days for a Review [2]. This is a great achievement by any standard. We look forward to your continuous support of Virology Journal either as an invited reviewer or a contributing author in the years to come.",2014 Jan 22,"Wang, Linfa",Virol J,,,True
2b2e83d49677c03c836133b83b909f5db0423cc9,PMC,Development of a novel clinical scoring system for on-farm diagnosis of bovine respiratory disease in pre-weaned dairy calves,http://dx.doi.org/10.7717/peerj.238,PMC3898311,24482759,CC BY,"Several clinical scoring systems for diagnosis of bovine respiratory disease (BRD) in calves have been proposed. However, such systems were based on subjective judgment, rather than statistical methods, to weight scores. Data from a pair-matched case-control study on a California calf raising facility was used to develop three novel scoring systems to diagnose BRD in preweaned dairy calves. Disease status was assigned using both clinical signs and diagnostic test results for BRD-associated pathogens. Regression coefficients were used to weight score values. The systems presented use nasal and ocular discharge, rectal temperature, ear and head carriage, coughing, and respiratory quality as predictors. The systems developed in this research utilize fewer severity categories of clinical signs, require less calf handling, and had excellent agreement (Kappa > 0.8) when compared to an earlier scoring system. The first scoring system dichotomized all clinical predictors but required inducing a cough. The second scoring system removed induced cough as a clinical abnormality but required distinguishing between three levels of nasal discharge severity. The third system removed induced cough and forced a dichotomized variable for nasal discharge. The first system presented in this study used the following predictors and assigned values: coughing (induced or spontaneous coughing, 2 points), nasal discharge (any discharge, 3 points), ocular discharge (any discharge, 2 points), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2°C or 102.5°F, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized “BRD positive” if their total score was ≥4. This system correctly classified 95.4% cases and 88.6% controls. The second presented system categorized the predictors and assigned weights as follows: coughing (spontaneous only, 2 points), mild nasal discharge (unilateral, serous, or watery discharge, 3 points), moderate to severe nasal discharge (bilateral, cloudy, mucoid, mucopurlent, or copious discharge, 5 points), ocular discharge (any discharge, 1 point), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2°C, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized “BRD positive” if their total score was ≥4. This system correctly classified 89.3% cases and 92.8% controls. The third presented system used the following predictors and scores: coughing (spontaneous only, 2 points), nasal discharge (any, 4 points), ocular discharge (any, 2 points), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2°C, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized “BRD positive” if their total score was ≥5. This system correctly classified 89.4% cases and 90.8% controls. Each of the proposed systems offer few levels of clinical signs and data-based weights for on-farm diagnosis of BRD in dairy calves.",2014 Jan 2,"['Love, William J.', 'Lehenbauer, Terry W.', 'Kass, Philip H.', 'Van Eenennaam, Alison L.', 'Aly, Sharif S.']",PeerJ,,,True
0a4a2763f35864555a20b296c1daf1614f09e28f,PMC,In Vitro and In Vivo Activity of a Novel Antifungal Small Molecule against Candida Infections,http://dx.doi.org/10.1371/journal.pone.0085836,PMC3899067,24465737,CC BY,"Candida is the most common fungal pathogen of humans worldwide and has become a major clinical problem because of the growing number of immunocompromised patients, who are susceptible to infection. Moreover, the number of available antifungals is limited, and antifungal-resistant Candida strains are emerging. New and effective antifungals are therefore urgently needed. Here, we discovered a small molecule with activity against Candida spp. both in vitro and in vivo. We screened a library of 50,240 small molecules for inhibitors of yeast-to-hypha transition, a major virulence attribute of Candida albicans. This screening identified 20 active compounds. Further examination of the in vitro antifungal and anti-biofilm properties of these compounds, using a range of Candida spp., led to the discovery of SM21, a highly potent antifungal molecule (minimum inhibitory concentration (MIC) 0.2 – 1.6 µg/ml). In vitro, SM21 was toxic to fungi but not to various human cell lines or bacterial species and was active against Candida isolates that are resistant to existing antifungal agents. Moreover, SM21 was relatively more effective against biofilms of Candida spp. than the current antifungal agents. In vivo, SM21 prevented the death of mice in a systemic candidiasis model and was also more effective than the common antifungal nystatin at reducing the extent of tongue lesions in a mouse model of oral candidiasis. Propidium iodide uptake assay showed that SM21 affected the integrity of the cell membrane. Taken together, our results indicate that SM21 has the potential to be developed as a novel antifungal agent for clinical use.",2014 Jan 22,"['Wong, Sarah Sze Wah', 'Kao, Richard Yi Tsun', 'Yuen, Kwok Yong', 'Wang, Yu', 'Yang, Dan', 'Samaranayake, Lakshman Perera', 'Seneviratne, Chaminda Jayampath']",PLoS One,,,True
8605d9a84e827e232a47861c65c61605c789acf7,PMC,Transmission of Pandemic Influenza A (H1N1) Virus in a Train in China,http://dx.doi.org/10.2188/jea.JE20100119,PMC3899419,21646746,CC BY,"BACKGROUND: Pandemic influenza A (H1N1) virus emerged in North America in April 2009 and spread globally. We describe the epidemiology and public health response to the first known outbreak of 2009 H1N1 in a train, which occurred in June 2009 in China. METHODS: After 2 provinces provided initial reports of 2009 H1N1 infection in 2 persons who had travelled on the same train, we conducted a retrospective epidemiologic investigation to collect information from the passengers, crew members, contacts, and health care providers. We explored the source of infection and possible routes of transmission in the train. All cases were confirmed by real-time reverse transcription polymerase chain reaction testing. RESULTS: Train #1223 traveled 40 hours, made 28 stops in 4 Chinese provinces, and boarded 2555 passengers, who logged a total of 59 144 person-hours of travel time. Nineteen confirmed 2009 H1N1 cases were identified. Of these, 13 were infected and developed symptoms on the train and 6 occurred among contacts who developed illness during medical monitoring. In addition, 3 asymptomatic cases were identified based on RT-PCR testing of respiratory swabs from contacts. The attack rate among contacts of confirmed cases in the same car was higher than that among contacts in other cars (3.15% vs. 0%, P < 0.001). Attack rates increased with exposure time. CONCLUSIONS: Close contact and long exposure may have contributed to the transmission of 2009 H1N1 virus in the train. Trains may have played an important role in the 2009 influenza pandemic.",2011 Jul 5,"['Cui, Fuqiang', 'Luo, Huiming', 'Zhou, Lei', 'Yin, Dapeng', 'Zheng, Canjun', 'Wang, Dingming', 'Gong, Jian', 'Fang, Gang', 'He, Jianfeng', 'McFarland, Jeffrey', 'Yu, Hongjie']",J Epidemiol,,,True
c8b1da52eeb1d7dc2ff2f2f20a44ef13160fd626,PMC,Sambucus nigra extracts inhibit infectious bronchitis virus at an early point during replication,http://dx.doi.org/10.1186/1746-6148-10-24,PMC3899428,24433341,CC BY,"BACKGROUND: Infectious bronchitis virus (IBV) is a pathogenic chicken coronavirus. Currently, vaccination against IBV is only partially protective; therefore, better preventions and treatments are needed. Plants produce antimicrobial secondary compounds, which may be a source for novel anti-viral drugs. Non-cytotoxic, crude ethanol extracts of Rhodiola rosea roots, Nigella sativa seeds, and Sambucus nigra fruit were tested for anti-IBV activity, since these safe, widely used plant tissues contain polyphenol derivatives that inhibit other viruses. RESULTS: Dose–response cytotoxicity curves on Vero cells using trypan blue staining determined the highest non-cytotoxic concentrations of each plant extract. To screen for IBV inhibition, cells and virus were pretreated with extracts, followed by infection in the presence of extract. Viral cytopathic effect was assessed visually following an additional 24 h incubation with extract. Cells and supernatants were harvested separately and virus titers were quantified by plaque assay. Variations of this screening protocol determined the effects of a number of shortened S. nigra extract treatments. Finally, S. nigra extract-treated virions were visualized by transmission electron microscopy with negative staining. Virus titers from infected cells treated with R. rosea and N. sativa extracts were not substantially different from infected cells treated with solvent alone. However, treatment with S. nigra extracts reduced virus titers by four orders of magnitude at a multiplicity of infection (MOI) of 1 in a dose-responsive manner. Infection at a low MOI reduced viral titers by six orders of magnitude and pretreatment of virus was necessary, but not sufficient, for full virus inhibition. Electron microscopy of virions treated with S. nigra extract showed compromised envelopes and the presence of membrane vesicles, which suggested a mechanism of action. CONCLUSIONS: These results demonstrate that S. nigra extract can inhibit IBV at an early point in infection, probably by rendering the virus non-infectious. They also suggest that future studies using S. nigra extract to treat or prevent IBV or other coronaviruses are warranted.",2014 Jan 16,"['Chen, Christie', 'Zuckerman, David M', 'Brantley, Susanna', 'Sharpe, Michka', 'Childress, Kevin', 'Hoiczyk, Egbert', 'Pendleton, Amanda R']",BMC Vet Res,,,True
45f6818a37c16f974f9be1d2e94e0ff5b9887c4d,PMC,"Attitudes, practices and information needs regarding novel influenza A (H7N9) among employees of food production and operation in Guangzhou, Southern China: a cross-sectional study",http://dx.doi.org/10.1186/1471-2334-14-4,PMC3899619,24383626,CC BY,"BACKGROUND: As of 30 May 2013, 132 human infections with avian influenza A (H7N9) had been reported in 10 Chinese cities. On 17 May 2013, because a chicken infection with H7 subtype avian influenza virus was detected in Guanzhou, Guangzhou became the 11th city to conduct emergency response operations. The goal of this study was to identify attitudes, practices and information needs among employees of food production and operation in Guangzhou. METHODS: A cross-sectional survey of face-to-face interviews was used during 17–24 June 2013. All adults seeking health examination in Guangzhou Center for Disease Control and Prevention who had lived in Guangzhou for at least 3 months, were engaged in food production and operation, and agreed to participate were interviewed. RESULTS: Of 1,450 participants, 69.72% worried about being infected with the A/H7N9 and 74.41% stated that they had searched for information about A/H7N9. The internet (76.92%), television (67.56%), and newspapers (56.26%) were the main methods of obtaining information; the use of these methods differed significantly by various demographic variables (P < 0.05). More than one-fifth of participants complained that the information was not timely enough (20.28%) and was intentionally concealed by the government (20.76%). Nearly one-third (32.35%) did not believe that the government could control the A/H7N9 epidemic. Most participants (80.76%) reported washing hands more frequently than before, while over one-third (37.17%) stated no longer buying poultry. A total of 84.00% indicated a willingness to receive an A/H7N9 vaccine, and the primary reason for not being willing was concern about safety (58.19%). A history of influenza vaccination and worry about being infected with the A/H7N9 were significantly associated with intention to receive an A/H7N9 vaccine (P < 0.05). CONCLUSIONS: Our findings provide insight into the attitudes and practices of employees of food production and operation 3 months after the first human A/H7N9 case reported in China, and 1 month after infected chickens were identified in Guangzhou. Distrust in the health department should be addressed, and more effort should be made to improve compliance of proper preventive measures to reduce panic among the public. The information needs should be taken into account in the next step of health education.",2014 Jan 2,"['Li, Tiegang', 'Feng, Jing', 'Qing, Pengzhe', 'Fan, Xiaomei', 'Liu, Weisi', 'Li, MeiXia', 'Wang, Ming']",BMC Infect Dis,,,True
48f553c843618f0cc189f9067685f551049a018f,PMC,Bayesian Reconstruction of Disease Outbreaks by Combining Epidemiologic and Genomic Data,http://dx.doi.org/10.1371/journal.pcbi.1003457,PMC3900386,24465202,CC BY,"Recent years have seen progress in the development of statistically rigorous frameworks to infer outbreak transmission trees (“who infected whom”) from epidemiological and genetic data. Making use of pathogen genome sequences in such analyses remains a challenge, however, with a variety of heuristic approaches having been explored to date. We introduce a statistical method exploiting both pathogen sequences and collection dates to unravel the dynamics of densely sampled outbreaks. Our approach identifies likely transmission events and infers dates of infections, unobserved cases and separate introductions of the disease. It also proves useful for inferring numbers of secondary infections and identifying heterogeneous infectivity and super-spreaders. After testing our approach using simulations, we illustrate the method with the analysis of the beginning of the 2003 Singaporean outbreak of Severe Acute Respiratory Syndrome (SARS), providing new insights into the early stage of this epidemic. Our approach is the first tool for disease outbreak reconstruction from genetic data widely available as free software, the R package outbreaker. It is applicable to various densely sampled epidemics, and improves previous approaches by detecting unobserved and imported cases, as well as allowing multiple introductions of the pathogen. Because of its generality, we believe this method will become a tool of choice for the analysis of densely sampled disease outbreaks, and will form a rigorous framework for subsequent methodological developments.",2014 Jan 23,"['Jombart, Thibaut', 'Cori, Anne', 'Didelot, Xavier', 'Cauchemez, Simon', 'Fraser, Christophe', 'Ferguson, Neil']",PLoS Comput Biol,,,True
1e3bb33ad4578e3e176b4c68fc4903d6541d9e80,PMC,Bayesian Reconstruction of Disease Outbreaks by Combining Epidemiologic and Genomic Data,http://dx.doi.org/10.1371/journal.pcbi.1003457,PMC3900386,24465202,CC BY,"Recent years have seen progress in the development of statistically rigorous frameworks to infer outbreak transmission trees (“who infected whom”) from epidemiological and genetic data. Making use of pathogen genome sequences in such analyses remains a challenge, however, with a variety of heuristic approaches having been explored to date. We introduce a statistical method exploiting both pathogen sequences and collection dates to unravel the dynamics of densely sampled outbreaks. Our approach identifies likely transmission events and infers dates of infections, unobserved cases and separate introductions of the disease. It also proves useful for inferring numbers of secondary infections and identifying heterogeneous infectivity and super-spreaders. After testing our approach using simulations, we illustrate the method with the analysis of the beginning of the 2003 Singaporean outbreak of Severe Acute Respiratory Syndrome (SARS), providing new insights into the early stage of this epidemic. Our approach is the first tool for disease outbreak reconstruction from genetic data widely available as free software, the R package outbreaker. It is applicable to various densely sampled epidemics, and improves previous approaches by detecting unobserved and imported cases, as well as allowing multiple introductions of the pathogen. Because of its generality, we believe this method will become a tool of choice for the analysis of densely sampled disease outbreaks, and will form a rigorous framework for subsequent methodological developments.",2014 Jan 23,"['Jombart, Thibaut', 'Cori, Anne', 'Didelot, Xavier', 'Cauchemez, Simon', 'Fraser, Christophe', 'Ferguson, Neil']",PLoS Comput Biol,,,False
83a6a45a591e9222cf68f14d60dce7d3c810c1f0,PMC,Resting of Cryopreserved PBMC Does Not Generally Benefit the Performance of Antigen-Specific T Cell ELISPOT Assays,http://dx.doi.org/10.3390/cells1030409,PMC3901103,24710483,CC BY,"T cell monitoring is increasingly performed using cryopreserved PBMC. It has been suggested that resting of PBMC after thawing, that is, culturing them overnight in test medium, produces higher antigen-induced spot counts in ELISPOT assays. To evaluate the importance of overnight resting, we systematically tested cryopreserved PBMC from 25 healthy donors. CEF peptides (comprising CMV, EBV and flu antigens) were used to stimulate CD8 cells and mumps antigen to stimulate CD4 cells. The data show that resting significantly increased antigen-elicited T cell responses only for CEF high responder PBMC. The maximal gain observed was doubling of spot counts. For CEF low responders, and for mumps responders of either low- or high reactivity levels, resting had no statistically significant effect on the observed spot counts. Therefore, resting is not a generally applicable approach to improve ELISPOT assay performance, but can be recommended only for clinical subject cohorts and antigens for which it has a proven benefit. Because resting invariably leads to losing about half of the PBMC available for testing, and because doubling the PBMC numbers plated into the assay reliably doubles the antigen-induced spot counts, we suggest the latter approach as a simple and reliable alternative to resting for enhancing the performance of ELISPOT assays. Our data imply that resting is not required if PBMC were cryopreserved and thawed under conditions that minimize apoptosis of the cells. Therefore, this study should draw attention to the need to optimize freezing and thawing conditions for successful T cell work.",2012 Jul 30,"['Kuerten, Stefanie', 'Batoulis, Helena', 'Recks, Mascha S.', 'Karacsony, Edith', 'Zhang, Wenji', 'Subbramanian, Ramu A.', 'Lehmann, Paul V.']",Cells,,,True
14898820328acb4f3dcf85f33f3addb113d5a97d,PMC,Modulation of Autophagy-Like Processes by Tumor Viruses,http://dx.doi.org/10.3390/cells1030204,PMC3901111,24710474,CC BY,"Autophagy is an intracellular degradation pathway for long-lived proteins and organelles. This process is activated above basal levels upon cell intrinsic or environmental stress and dysregulation of autophagy has been linked to various human diseases, including those caused by viral infection. Many viruses have evolved strategies to directly interfere with autophagy, presumably to facilitate their replication or to escape immune detection. However, in some cases, modulation of autophagy appears to be a consequence of the virus disturbing the cell’s metabolic signaling networks. Here, we summarize recent advances in research at the interface of autophagy and viral infection, paying special attention to strategies that human tumor viruses have evolved.",2012 Jun 25,"['Mack, Hildegard I. D.', 'Munger, Karl']",Cells,,,True
4a64ef9057367aec43ce6b8a40e9bb0c9587fdf4,PMC,Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats,http://dx.doi.org/10.3390/cells1041168,PMC3901151,24710549,CC BY,"Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH). Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture.",2012 Dec 5,"['Zhang, Qing', 'Miller, Christopher', 'Bible, Jesse', 'Li, Jiliang', 'Xu, Xiaoqing', 'Mehta, Nozer', 'Gilligan, James', 'Vignery, Agnès', 'Scholz, Jodi A Carlson']",Cells,,,True
89e039e0e861069bedfb158e43844d3730b5abbb,PMC,Functional Polymorphisms of Interferon-gamma Affect Pneumonia-Induced Sepsis,http://dx.doi.org/10.1371/journal.pone.0087049,PMC3901723,24475220,CC BY,"OBJECTIVE: Sepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high. Because interferon-gamma (IFN-γ) plays an important role in inflammation, this work assessed IFN-γ single nucleotide polymorphism (SNPs) that may be associated with sepsis. METHODS: A total of 196 patients with pneumonia-induced sepsis and 213 age- and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China. Patient clinical information was collected. Clinical pathology was assessed in subgroups defined based on clinical criteria, APACHE II (acute physiology and chronic health evaluation) and SOFA (sepsis-related organ failure assessment) scores and discharge rate. Four functional SNPs, −1616T/C (rs2069705), −764G/C (rs2069707), +874A/T (rs2430561) and +3234C/T (rs2069718), were genotyped by Snapshot in both sepsis patients and healthy controls. Pearson’s chi-square test or Fisher’s exact test were used to analyze the distribution of the SNPs, and the probability values (P values), odds ratios (OR) and 95% confidence intervals (CIs) were calculated. RESULTS: No mutations in the IFN-γ −764G/C SNP were detected among the participants in our study. The +874A/T and +3234C/T SNPs were in strong linkage disequilibrium (LD) (r(2) = 0.894). The −1616 TC+TT, +874 AT+AA genotype and the TAC haplotype were significantly associated with sepsis susceptibility, while the CTT haplotype was associated with protection against sepsis incidence. Genotype of −1616 TT wasn’t only protective against severity of sepsis, but also against higher APACHE II and SOFA scores as +874 AA and +3234 CC. The TAC haplotype was was protective against progression to severe sepsis either. CONCLUSION: Our results suggest that functional IFN-γ SNPs and their haplotypes are associated with pneumonia-induced sepsis.",2014 Jan 24,"['Wang, Ding', 'Zhong, Xuan', 'Huang, Dongjian', 'Chen, Rui', 'Bai, Guibin', 'Li, Qing', 'Yu, Bolan', 'Fan, Yong', 'Sun, Xiaofang']",PLoS One,,,True
b010b3bb7db4f358b0ec2829523ccbfd6d52afbc,PMC,Cost-effective length and timing of school closure during an influenza pandemic depend on the severity,http://dx.doi.org/10.1186/1742-4682-11-5,PMC3901768,24447310,CC BY,"BACKGROUND: There has been a variation in published opinions toward the effectiveness of school closure which is implemented reactively when substantial influenza transmissions are seen at schools. Parameterizing an age-structured epidemic model using published estimates of the pandemic H1N1-2009 and accounting for the cost effectiveness, we examined if the timing and length of school closure could be optimized. METHODS: Age-structured renewal equation was employed to describe the epidemic dynamics of an influenza pandemic. School closure was assumed to take place only once during the course of the pandemic, abruptly reducing child-to-child transmission for a fixed length of time and also influencing the transmission between children and adults. Public health effectiveness was measured by reduction in the cumulative incidence, and cost effectiveness was also examined by calculating the incremental cost effectiveness ratio and adopting a threshold of 1.0 × 10(7) Japanese Yen/life-year. RESULTS: School closure at the epidemic peak appeared to yield the largest reduction in the final size, while the time of epidemic peak was shown to depend on the transmissibility. As the length of school closure was extended, we observed larger reduction in the cumulative incidence. Nevertheless, the cost effectiveness analysis showed that the cost of our school closure scenario with the parameters derived from H1N1-2009 was not justifiable. If the risk of death is three times or greater than that of H1N1-2009, the school closure could be regarded as cost effective. CONCLUSIONS: There is no fixed timing and duration of school closure that can be recommended as universal guideline for different types of influenza viruses. The effectiveness of school closure depends on the transmission dynamics of a particular influenza virus strain, especially the virulence (i.e. the infection fatality risk).",2014 Jan 21,"['Nishiura, Hiroshi', 'Ejima, Keisuke', 'Mizumoto, Kenji', 'Nakaoka, Shinji', 'Inaba, Hisashi', 'Imoto, Seiya', 'Yamaguchi, Rui', 'Saito, Masaya M']",Theor Biol Med Model,,,True
e141a069b6f6aef31ddf1a2ae592933db0b4a031,PMC,Discovery of functional genomic motifs in viruses with ViReMa–a Virus Recombination Mapper–for analysis of next-generation sequencing data,http://dx.doi.org/10.1093/nar/gkt916,PMC3902915,24137010,CC BY,"We developed an algorithm named ViReMa (Viral-Recombination-Mapper) to provide a versatile platform for rapid, sensitive and nucleotide-resolution detection of recombination junctions in viral genomes using next-generation sequencing data. Rather than mapping read segments of pre-defined lengths and positions, ViReMa dynamically generates moving read segments. ViReMa initially attempts to align the 5′ end of a read to the reference genome(s) with the Bowtie seed-based alignment. A new read segment is then made by either extracting any unaligned nucleotides at the 3′ end of the read or by trimming the first nucleotide from the read. This continues iteratively until all portions of the read are either mapped or trimmed. With multiple reference genomes, it is possible to detect virus-to-host or inter-virus recombination. ViReMa is also capable of detecting insertion and substitution events and multiple recombination junctions within a single read. By mapping the distribution of recombination events in the genome of flock house virus, we demonstrate that this information can be used to discover de novo functional motifs located in conserved regions of the viral genome.",2014 Jan 9,"['Routh, Andrew', 'Johnson, John E.']",Nucleic Acids Res,,,True
7d8f6f7c012e065e971832e990bcf5b9b5bc6928,PMC,High-Throughput Screening to Identify Plant Derived Human LDH-A Inhibitors,,PMC3903096,24478981,CC BY,"AIMS: Lactate dehydrogenase (LDH)-A is highly expressed in diverse human malignant tumors, parallel to aggressive metastatic disease, resistance to radiation/chemotherapy and clinically poor outcome. Although this enzyme constitutes a plausible target in treatment of advanced cancer, there are few known LDH-A inhibitors. STUDY DESIGN: In this work, we utilized a high-throughput enzyme micro-array format to screen and evaluate > 900 commonly used medicinal plant extracts (0.00001-.5 mg/ml) for capacity to inhibit activity of recombinant full length human LDHA; EC .1.1.1.27. METHODOLOGY: The protein sequence of purified enzyme was confirmed using 1D gel electrophoresis- MALDI-TOF-MS/MS, enzyme activity was validated by oxidation of NADH (500μM) and kinetic inhibition established in the presence of a known inhibitor (Oxalic Acid). RESULTS: Of the natural extracts tested, the lowest IC(50)s [<0.001 mg/ml] were obtained by: Chinese Gallnut (Melaphis chinensis gallnut), Bladderwrack (Fucus vesiculosus), Kelp (Laminaria Japonica) and Babul (Acacia Arabica). Forty-six additional herbs contained significant LDH-A inhibitory properties with IC(50)s [<0.07 mg/ml], some of which have common names of Arjun, Pipsissewa, Cinnamon, Pink Rose Buds/Petals, Wintergreen, Cat’s Claw, Witch Hazel Root and Rhodiola Root. CONCLUSION: These findings reflect relative potency by rank of commonly used herbs and plants that contain human LDH-A inhibitory properties. Future research will be required to isolate chemical constituents within these plants responsible for LDH-A inhibition and investigate potential therapeutic application.",2013,"['Deiab, S.', 'Mazzio, E.', 'Messeha, S.', 'Mack, N.', 'Soliman, K. F. A.']",European J Med Plants,,,True
f18489a27432115deff5b9be2dd2e0af9d8409a5,PMC,Comparison of Road Traffic Injury Characteristics between Local versus Floating Migrant Patients in a Tertiary Hospital between 2007 and 2010,http://dx.doi.org/10.1371/journal.pone.0082640,PMC3903469,24475023,CC BY,"BACKGROUND: The aim of this study is to give a description of the road traffic injuries (RTIs) characteristics of floating migrant population by comparing with those of local residents in a harbor city of China. METHODS: A population-based descriptive study was carried out between 2007 and 2010 with RTI patient records from the Fifth Center Hospital of Tianjin. Inpatient diagnoses of RTI patients were defined using the International Classification of Diseases, Tenth Revision (ICD-10) codes. We analyzed the demographics and general characteristics of RTI patients that were in the hospital during the four years. In order to compare the group differences between local resident patients and floating migrant patients, the distribution of their ages, diagnoses, severity of injuries, duration of inpatient stays, hospitalization cost were analyzed. RESULTS: People between the ages of 16 and 55 were the most likely to suffer RTIs. The floating migrant patients between the ages of 16 and 45 had a higher incidence of accidents, while local resident patients between 46 and 55 had a higher incidence of accidents. Compared to local resident patients, floating migrant patients were more vulnerable to open injuries and severe traffic injuries. With the severity of injuries ranked from mild to severe, floating migrant patients had lower duration of inpatient stay, but higher hospitalization costs compared to local resident patients. CONCLUSIONS: Floating migrant patients had a different age distribution, severity of injuries, diseases, inpatient duration and hospitalization cost compared with local resident patients. Compared to local resident patients, floating migrants had a higher risk to RTIs and were more vulnerable to severer traffic accidents at lower ages.",2014 Jan 27,"['Xu, Chungui', 'Wang, Yanhua', 'Han, Na', 'Kou, Yuhui', 'Yin, Xiaofeng', 'Zhang, Peixun', 'Wang, Tianbing', 'Zhang, Dianying', 'Jiang, Baoguo']",PLoS One,,,True
d876d3d89d579f47df9ac251a4139ab1051561f5,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,True
7c4692c36869c3dfbd3507e70bdd74c11a0abec4,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
259ccfb33a20277e36150d6aad3ad88052123d15,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
31a504112c9e2d723989d5dbc83b2d14268b5d00,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
d332e54ea99c5fb3db1c18e6a4625aa7ace6ef31,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
392acb54f5179e12c68b78659be5d45df986707b,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
699bd0d52187342c078470d7d3d52f2046557830,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
2744c8c3be800ae8061c5cceb36d06d5d426b8a0,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
6624feb71eb178c0bf6ad26181e82432e634f991,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
f8feadd4392a7a0a031d1d0343f561ad9fd98370,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
470d07fc69e326fb26f10d21c103696232b021d2,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
5e77269850b7b4bf57514e226ea66cd48ac31db5,PMC,Profiling of Glycan Receptors for Minute Virus of Mice in Permissive Cell Lines Towards Understanding the Mechanism of Cell Recognition,http://dx.doi.org/10.1371/journal.pone.0086909,PMC3903596,24475195,CC BY,"The recognition of sialic acids by two strains of minute virus of mice (MVM), MVMp (prototype) and MVMi (immunosuppressive), is an essential requirement for successful infection. To understand the potential for recognition of different modifications of sialic acid by MVM, three types of capsids, virus-like particles, wild type empty (no DNA) capsids, and DNA packaged virions, were screened on a sialylated glycan microarray (SGM). Both viruses demonstrated a preference for binding to 9-O-methylated sialic acid derivatives, while MVMp showed additional binding to 9-O-acetylated and 9-O-lactoylated sialic acid derivatives, indicating recognition differences. The glycans recognized contained a type-2 Galβ1-4GlcNAc motif (Neu5Acα2-3Galβ1-4GlcNAc or 3′SIA-LN) and were biantennary complex-type N-glycans with the exception of one. To correlate the recognition of the 3′SIA-LN glycan motif as well as the biantennary structures to their natural expression in cell lines permissive for MVMp, MVMi, or both strains, the N- and O-glycans, and polar glycolipids present in three cell lines used for in vitro studies, A9 fibroblasts, EL4 T lymphocytes, and the SV40 transformed NB324K cells, were analyzed by MALDI-TOF/TOF mass spectrometry. The cells showed an abundance of the sialylated glycan motifs recognized by the viruses in the SGM and previous glycan microarrays supporting their role in cellular recognition by MVM. Significantly, the NB324K showed fucosylation at the non-reducing end of their biantennary glycans, suggesting that recognition of these cells is possibly mediated by the Lewis X motif as in 3′SIA-Le(X) identified in a previous glycan microarray screen.",2014 Jan 27,"['Halder, Sujata', 'Cotmore, Susan', 'Heimburg-Molinaro, Jamie', 'Smith, David F.', 'Cummings, Richard D.', 'Chen, Xi', 'Trollope, Alana J.', 'North, Simon J.', 'Haslam, Stuart M.', 'Dell, Anne', 'Tattersall, Peter', 'McKenna, Robert', 'Agbandje-McKenna, Mavis']",PLoS One,,,True
df1017e24101a51f6b5ca30ae2cb8376d8756a61,PMC,Dietary Enterococcus faecium NCIMB 10415 and Zinc Oxide Stimulate Immune Reactions to Trivalent Influenza Vaccination in Pigs but Do Not Affect Virological Response upon Challenge Infection,http://dx.doi.org/10.1371/journal.pone.0087007,PMC3904981,24489827,CC BY,"Swine influenza viruses (SIV) regularly cause significant disease in pigs worldwide. Since there is no causative treatment of SIV, we tested if probiotic Enterococcus (E.) faecium NCIMB 10415 or zinc (Zn) oxide as feed supplements provide beneficial effects upon SIV infection in piglets. Seventy-two weaned piglets were fed three different diets containing either E. faecium or different levels of Zn (2500 ppm, Zn(high); 50 ppm, Zn(low)). Half of the piglets were vaccinated intramuscularly (VAC) twice with an inactivated trivalent SIV vaccine, while all piglets were then infected intranasally with H3N2 SIV. Significantly higher weekly weight gains were observed in the E. faecium group before virus infection, and piglets in Zn(high) and E. faecium groups gained weight after infection while those in the control group (Zn(low)) lost weight. Using ELISA, we found significantly higher H3N2-specific antibody levels in the E. faecium+VAC group 2 days before and at the day of challenge infection as well as at 4 and 6 days after challenge infection. Higher hemagglutination inhibition (HI) titers were also observed in the Zn(high)+VAC and E. faecium+VAC groups at 0, 1 and 4 days after infection. However, there were no significant differences in virus shedding and lung lesions between the dietary groups. Using flow cytometry analysis significantly higher activated T helper cells and cytotoxic T lymphocyte percentages in the PBMCs were detected in the Zn(high) and E. faecium groups at single time points after infection compared to the Zn(low) control group, but no prolonged effect was found. In the BAL cells no influence of dietary supplementation on immune cell percentages could be detected. Our results suggest that feeding high doses of zinc oxide and particularly E. faecium could beneficially influence humoral immune responses after vaccination and recovery from SIV infection, but not affect virus shedding and lung pathology.",2014 Jan 28,"['Wang, Zhenya', 'Burwinkel, Michael', 'Chai, Weidong', 'Lange, Elke', 'Blohm, Ulrike', 'Breithaupt, Angele', 'Hoffmann, Bernd', 'Twardziok, Sven', 'Rieger, Juliane', 'Janczyk, Pawel', 'Pieper, Robert', 'Osterrieder, Nikolaus']",PLoS One,,,True
8ec3cfefcf560550c37dbc48107102bf2c893036,PMC,A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses,http://dx.doi.org/10.1371/journal.pone.0087194,PMC3906132,24489870,CC BY,"The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome). We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs). Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae). In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.",2014 Jan 29,"['Dacheux, Laurent', 'Cervantes-Gonzalez, Minerva', 'Guigon, Ghislaine', 'Thiberge, Jean-Michel', 'Vandenbogaert, Mathias', 'Maufrais, Corinne', 'Caro, Valérie', 'Bourhy, Hervé']",PLoS One,,,True
33748091ef717d6cf46b0677a1d5592c48d7581e,PMC,A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses,http://dx.doi.org/10.1371/journal.pone.0087194,PMC3906132,24489870,CC BY,"The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome). We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs). Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae). In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.",2014 Jan 29,"['Dacheux, Laurent', 'Cervantes-Gonzalez, Minerva', 'Guigon, Ghislaine', 'Thiberge, Jean-Michel', 'Vandenbogaert, Mathias', 'Maufrais, Corinne', 'Caro, Valérie', 'Bourhy, Hervé']",PLoS One,,,False
3114faaa4d11f6f05bd4702280615e2f8b44f488,PMC,A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses,http://dx.doi.org/10.1371/journal.pone.0087194,PMC3906132,24489870,CC BY,"The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome). We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs). Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae). In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.",2014 Jan 29,"['Dacheux, Laurent', 'Cervantes-Gonzalez, Minerva', 'Guigon, Ghislaine', 'Thiberge, Jean-Michel', 'Vandenbogaert, Mathias', 'Maufrais, Corinne', 'Caro, Valérie', 'Bourhy, Hervé']",PLoS One,,,False
e07b6453dffb63c7ca686ce8e5772422f987d3e5,PMC,A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses,http://dx.doi.org/10.1371/journal.pone.0087194,PMC3906132,24489870,CC BY,"The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome). We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs). Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae). In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.",2014 Jan 29,"['Dacheux, Laurent', 'Cervantes-Gonzalez, Minerva', 'Guigon, Ghislaine', 'Thiberge, Jean-Michel', 'Vandenbogaert, Mathias', 'Maufrais, Corinne', 'Caro, Valérie', 'Bourhy, Hervé']",PLoS One,,,False
da9beea6cc4a217fb31b54caf455ca229bf8a27b,PMC,A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses,http://dx.doi.org/10.1371/journal.pone.0087194,PMC3906132,24489870,CC BY,"The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome). We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs). Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae). In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.",2014 Jan 29,"['Dacheux, Laurent', 'Cervantes-Gonzalez, Minerva', 'Guigon, Ghislaine', 'Thiberge, Jean-Michel', 'Vandenbogaert, Mathias', 'Maufrais, Corinne', 'Caro, Valérie', 'Bourhy, Hervé']",PLoS One,,,False
57935bbfea5e9eb4e25ef185f059ebb4362714d8,PMC,A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses,http://dx.doi.org/10.1371/journal.pone.0087194,PMC3906132,24489870,CC BY,"The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome). We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs). Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae). In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.",2014 Jan 29,"['Dacheux, Laurent', 'Cervantes-Gonzalez, Minerva', 'Guigon, Ghislaine', 'Thiberge, Jean-Michel', 'Vandenbogaert, Mathias', 'Maufrais, Corinne', 'Caro, Valérie', 'Bourhy, Hervé']",PLoS One,,,False
af28c7f2e54f09c2ee5ea579d8646768a3be25c6,PMC,A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses,http://dx.doi.org/10.1371/journal.pone.0087194,PMC3906132,24489870,CC BY,"The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome). We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs). Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae). In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.",2014 Jan 29,"['Dacheux, Laurent', 'Cervantes-Gonzalez, Minerva', 'Guigon, Ghislaine', 'Thiberge, Jean-Michel', 'Vandenbogaert, Mathias', 'Maufrais, Corinne', 'Caro, Valérie', 'Bourhy, Hervé']",PLoS One,,,True
a04371951c94976a9b879f321764eb6dbeb4a9ab,PMC,Effect of Glycyrrhizin on Pseudomonal Skin Infections in Human-Mouse Chimeras,http://dx.doi.org/10.1371/journal.pone.0083747,PMC3907411,24497916,CC BY,"In our previous studies, peripheral blood lineage(−)CD34(+)CD31(+) cells (CD31(+) IMC) appearing in severely burned patients have been characterized as inhibitor cells for the production of β-defensins (HBDs) by human epidermal keratinocytes (NHEK). In this study, the effect of glycyrrhizin on pseudomonal skin infections was studied in a chimera model of thermal injury. Two different chimera models were utilized. Patient chimeras were created in murine antimicrobial peptide-depleted NOD-SCID IL-2rγ(null) mice that were grafted with unburned skin tissues of severely burned patients and inoculated with the same patient peripheral blood CD31(+) IMC. Patient chimera substitutes were created in the same mice that were grafted with NHEK and inoculated with experimentally induced CD31(+) IMC. In the results, both groups of chimeras treated with glycyrrhizin resisted a 20 LD(50) dose of P. aeruginosa skin infection, while all chimeras in both groups treated with saline died within 3 days of the infection. Human antimicrobial peptides were detected from the grafted site tissues of both groups of chimeras treated with glycyrrhizin, while the peptides were not detected in the same area tissues of controls. HBD-1 was produced by keratinocytes in transwell-cultures performed with CD31(+) IMC and glycyrrhizin. Also, inhibitors (IL-10 and CCL2) of HBD-1 production by keratinocytes were not detected in cultures of patient CD31(+) IMC treated with glycyrrhizin. These results indicate that sepsis stemming from pseudomonal grafted site infections in a chimera model of burn injury is controllable by glycyrrhizin. Impaired antimicrobial peptide production at the infection site of severely burned patients may be restored after treatment with glycyrrhizin.",2014 Jan 30,"['Yoshida, Shohei', 'Lee, Jong O.', 'Nakamura, Kiwamu', 'Suzuki, Sumihiro', 'Hendon, David N.', 'Kobayashi, Makiko', 'Suzuki, Fujio']",PLoS One,,,True
66d172659a7156097bd453af7028c06632c231a5,PMC,Cross sectional survey of human-bat interaction in Australia: public health implications,http://dx.doi.org/10.1186/1471-2458-14-58,PMC3908316,24443960,CC BY,"BACKGROUND: Flying foxes (megachiroptera) and insectivorous microbats (microchiroptera) are the known reservoirs for a range of recently emerged, highly pathogenic viruses. In Australia there is public health concern relating to bats’ role as reservoirs of Australian Bat Lyssavirus (ABLV), which has clinical features identical to classical rabies. Three deaths from ABLV have occurred in Australia. A survey was conducted to determine the frequency of bat exposures amongst adults in Australia’s most populous state, New South Wales; explore reasons for handling bats; examine reported practices upon encountering injured or trapped bats or experiencing bat bites or scratches; and investigate knowledge of bat handling warnings. METHODS: A representative sample of 821 New South Wales adults aged 16 years and older were interviewed during May and June 2011, using a computer assisted telephone interview (CATI) method. Frequencies, proportions and statistical differences in proportion were performed. Using an α-value of 0.05 and power of 80%, it was calculated that a sample size of 800 was required to provide statistical significance of +/− 5% for dichotomous variables. RESULTS: One-hundred-and-twenty-seven (15.5%) respondents indicated that they had previously handled a bat, being 22% (48/218) rural and 13% (78/597) urban respondents (χ(2) = 9.8, p = 0.0018). Twenty one percent of males (63/304) had handled bats compared with 12% (64/517) of females (χ(2) = 10.2, p = 0.0014). Overall, 42.0% (n = 345) of respondents reported having seen or heard a warning about handling bats. If faced with an injured or trapped bat, 25% (206/821) indicated that they would handle the bat, with 17% (36/206) saying that they would use their bare hands. For minor scratches, 14% (117/821) indicated that they would ignore the injury while four respondents would ignore major scratches or bites. CONCLUSIONS: Previous human-bat interactions were relatively common. Bat exposures most frequently occurred with sick or injured bats, which have the highest risk of ABLV. On encountering an injured or sick bat, potentially high risk practices were commonly reported, particularly among rural males. It is important to understand why people still handle bats despite public health warnings to inform future communication strategies.",2014 Jan 21,"['Paterson, Beverley J', 'Butler, Michelle T', 'Eastwood, Keith', 'Cashman, Patrick M', 'Jones, Alison', 'Durrheim, David N']",BMC Public Health,,,True
8589358e390499b6c9d95a5eb20b0bfb4bc75466,PMC,Idiopathic acute myocarditis during treatment for controlled human malaria infection: a case report,http://dx.doi.org/10.1186/1475-2875-13-38,PMC3909449,24479524,CC BY,"A 23-year-old healthy male volunteer took part in a clinical trial in which the volunteer took chloroquine chemoprophylaxis and received three intradermal doses at four-week intervals of aseptic, purified Plasmodium falciparum sporozoites to induce protective immunity against malaria. Fifty-nine days after the last administration of sporozoites and 32 days after the last dose of chloroquine the volunteer underwent controlled human malaria infection (CHMI) by the bites of five P. falciparum-infected mosquitoes. Eleven days post-CHMI a thick blood smear was positive (6 P. falciparum/μL blood) and treatment was initiated with atovaquone/proguanil (Malarone®). On the second day of treatment, day 12 post-CHMI, troponin T, a marker for cardiac tissue damage, began to rise above normal, and reached a maximum of 1,115 ng/L (upper range of normal = 14 ng/L) on day 16 post-CHMI. The volunteer had one ~20 minute episode of retrosternal chest pain and heavy feeling in his left arm on day 14 post-CHMI. ECG at the time revealed minor repolarization disturbances, and cardiac MRI demonstrated focal areas of subepicardial and midwall delayed enhancement of the left ventricle with some oedema and hypokinesia. A diagnosis of myocarditis was made. Troponin T levels were normal within 16 days and the volunteer recovered without clinical sequelae. Follow-up cardiac MRI at almost five months showed normal function of both ventricles and disappearance of oedema. Delayed enhancement of subepicardial and midwall regions decreased, but was still present. With the exception of a throat swab that was positive for rhinovirus on day 14 post-CHMI, no other tests for potential aetiologies of the myocarditis were positive. A number of possible aetiological factors may explain or have contributed to this case of myocarditis including, i) P. falciparum infection, ii) rhinovirus infection, iii) unidentified pathogens, iv) hyper-immunization (the volunteer received six travel vaccines between the last immunization and the CHMI), v) atovaquone/proguanil treatment, or vi) a combination of these factors. Definitive aetiology and pathophysiological mechanism for the myocarditis have not been established.",2014 Jan 30,"['van Meer, Maurits PA', 'Bastiaens, Guido JH', 'Boulaksil, Mohamed', 'de Mast, Quirijn', 'Gunasekera, Anusha', 'Hoffman, Stephen L', 'Pop, Gheorghe', 'van der Ven, André JAM', 'Sauerwein, Robert W']",Malar J,,,True
7115c4bf2dfc029be764f0cd2e13de0bf8ec1312,PMC,Long-Distance Travel Behaviours Accelerate and Aggravate the Large-Scale Spatial Spreading of Infectious Diseases,http://dx.doi.org/10.1155/2014/295028,PMC3910471,24511324,CC BY,"The study analyses the role of long-distance travel behaviours on the large-scale spatial spreading of directly transmitted infectious diseases, focusing on two different travel types in terms of the travellers travelling to a specific group or not. For this purpose, we have formulated and analysed a metapopulation model in which the individuals in each subpopulation are organised into a scale-free contact network. The long-distance travellers between the subpopulations will temporarily change the network structure of the destination subpopulation through the “merging effects (MEs),” which indicates that the travellers will be regarded as either connected components or isolated nodes in the contact network. The results show that the presence of the MEs has constantly accelerated the transmission of the diseases and aggravated the outbreaks compared to the scenario in which the diversity of the long-distance travel types is arbitrarily discarded. Sensitivity analyses show that these results are relatively constant regarding a wide range variation of several model parameters. Our study has highlighted several important causes which could significantly affect the spatiotemporal disease dynamics neglected by the present studies.",2014 Jan 8,"['Xu, Zhijing', 'Zu, Zhenghu', 'Zheng, Tao', 'Zhang, Wendou', 'Xu, Qing', 'Liu, Jinjie']",Comput Math Methods Med,,,True
7261e8caea6deec22cee8f20ba55074a99b11e60,PMC,Powerful Sequence Similarity Search Methods and In-Depth Manual Analyses Can Identify Remote Homologs in Many Apparently “Orphan” Viral Proteins,http://dx.doi.org/10.1128/JVI.02595-13,PMC3911697,24155369,CC BY,"The genome sequences of new viruses often contain many “orphan” or “taxon-specific” proteins apparently lacking homologs. However, because viral proteins evolve very fast, commonly used sequence similarity detection methods such as BLAST may overlook homologs. We analyzed a data set of proteins from RNA viruses characterized as “genus specific” by BLAST. More powerful methods developed recently, such as HHblits or HHpred (available through web-based, user-friendly interfaces), could detect distant homologs of a quarter of these proteins, suggesting that these methods should be used to annotate viral genomes. In-depth manual analyses of a subset of the remaining sequences, guided by contextual information such as taxonomy, gene order, or domain cooccurrence, identified distant homologs of another third. Thus, a combination of powerful automated methods and manual analyses can uncover distant homologs of many proteins thought to be orphans. We expect these methodological results to be also applicable to cellular organisms, since they generally evolve much more slowly than RNA viruses. As an application, we reanalyzed the genome of a bee pathogen, Chronic bee paralysis virus (CBPV). We could identify homologs of most of its proteins thought to be orphans; in each case, identifying homologs provided functional clues. We discovered that CBPV encodes a domain homologous to the Alphavirus methyltransferase-guanylyltransferase; a putative membrane protein, SP24, with homologs in unrelated insect viruses and insect-transmitted plant viruses having different morphologies (cileviruses, higreviruses, blunerviruses, negeviruses); and a putative virion glycoprotein, ORF2, also found in negeviruses. SP24 and ORF2 are probably major structural components of the virions.",2014 Jan,"['Kuchibhatla, Durga B.', 'Sherman, Westley A.', 'Chung, Betty Y. W.', 'Cook, Shelley', 'Schneider, Georg', 'Eisenhaber, Birgit', 'Karlin, David G.']",J Virol,,,False
db62bc4bb76fa5755a43e79b6da62374886f2439,PMC,Powerful Sequence Similarity Search Methods and In-Depth Manual Analyses Can Identify Remote Homologs in Many Apparently “Orphan” Viral Proteins,http://dx.doi.org/10.1128/JVI.02595-13,PMC3911697,24155369,CC BY,"The genome sequences of new viruses often contain many “orphan” or “taxon-specific” proteins apparently lacking homologs. However, because viral proteins evolve very fast, commonly used sequence similarity detection methods such as BLAST may overlook homologs. We analyzed a data set of proteins from RNA viruses characterized as “genus specific” by BLAST. More powerful methods developed recently, such as HHblits or HHpred (available through web-based, user-friendly interfaces), could detect distant homologs of a quarter of these proteins, suggesting that these methods should be used to annotate viral genomes. In-depth manual analyses of a subset of the remaining sequences, guided by contextual information such as taxonomy, gene order, or domain cooccurrence, identified distant homologs of another third. Thus, a combination of powerful automated methods and manual analyses can uncover distant homologs of many proteins thought to be orphans. We expect these methodological results to be also applicable to cellular organisms, since they generally evolve much more slowly than RNA viruses. As an application, we reanalyzed the genome of a bee pathogen, Chronic bee paralysis virus (CBPV). We could identify homologs of most of its proteins thought to be orphans; in each case, identifying homologs provided functional clues. We discovered that CBPV encodes a domain homologous to the Alphavirus methyltransferase-guanylyltransferase; a putative membrane protein, SP24, with homologs in unrelated insect viruses and insect-transmitted plant viruses having different morphologies (cileviruses, higreviruses, blunerviruses, negeviruses); and a putative virion glycoprotein, ORF2, also found in negeviruses. SP24 and ORF2 are probably major structural components of the virions.",2014 Jan,"['Kuchibhatla, Durga B.', 'Sherman, Westley A.', 'Chung, Betty Y. W.', 'Cook, Shelley', 'Schneider, Georg', 'Eisenhaber, Birgit', 'Karlin, David G.']",J Virol,,,True
a5243628f77d40d5861c26212a3cc3102d9b2449,PMC,"Clinical Epidemiology of Bocavirus, Rhinovirus, Two Polyomaviruses and Four Coronaviruses in HIV-Infected and HIV-Uninfected South African Children",http://dx.doi.org/10.1371/journal.pone.0086448,PMC3911925,24498274,CC BY,"BACKGROUND: Advances in molecular diagnostics have implicated newly-discovered respiratory viruses in the pathogenesis of pneumonia. We aimed to determine the prevalence and clinical characteristics of human bocavirus (hBoV), human rhinovirus (hRV), polyomavirus-WU (WUPyV) and –KI (KIPyV) and human coronaviruses (CoV)-OC43, -NL63, -HKU1 and -229E among children hospitalized with lower respiratory tract infections (LRTI). METHODS: Multiplex real-time reverse-transcriptase polymerase chain reaction was undertaken on archived nasopharyngeal aspirates from HIV-infected and –uninfected children (<2 years age) hospitalized for LRTI, who had been previously investigated for respiratory syncytial virus, human metapneumovirus, parainfluenza I–III, adenovirus and influenza A/B. RESULTS: At least one of these viruses were identified in 274 (53.0%) of 517 and in 509 (54.0%) of 943 LRTI-episodes in HIV-infected and -uninfected children, respectively. Human rhinovirus was the most prevalent in HIV-infected (31.7%) and –uninfected children (32.0%), followed by CoV-OC43 (12.2%) and hBoV (9.5%) in HIV-infected; and by hBoV (13.3%) and WUPyV (11.9%) in HIV-uninfected children. Polyomavirus-KI (8.9% vs. 4.8%; p = 0.002) and CoV-OC43 (12.2% vs. 3.6%; p<0.001) were more prevalent in HIV-infected than –uninfected children. Combined with previously-tested viruses, respiratory viruses were identified in 60.9% of HIV-infected and 78.3% of HIV-uninfected children. The newly tested viruses were detected at high frequency in association with other respiratory viruses, including previously-investigated viruses (22.8% in HIV-infected and 28.5% in HIV–uninfected children). CONCLUSIONS: We established that combined with previously-investigated viruses, at least one respiratory virus was identified in the majority of HIV-infected and HIV-uninfected children hospitalized for LRTI. The high frequency of viral co-infections illustrates the complexities in attributing causality to specific viruses in the aetiology of LRTI and may indicate a synergetic role of viral co-infections in the pathogenesis of childhood LRTI.",2014 Feb 3,"['Nunes, Marta C.', 'Kuschner, Zachary', 'Rabede, Zelda', 'Madimabe, Richard', 'Van Niekerk, Nadia', 'Moloi, Jackie', 'Kuwanda, Locadiah', 'Rossen, John W.', 'Klugman, Keith P.', 'Adrian, Peter V.', 'Madhi, Shabir A.']",PLoS One,,,True
347209baac4ddbcc1533979d1a496128d7834f5e,PMC,Public knowledge and preventive behavior during a large-scale Salmonella outbreak: results from an online survey in the Netherlands,http://dx.doi.org/10.1186/1471-2458-14-100,PMC3913330,24479614,CC BY,"BACKGROUND: Food-borne Salmonella infections are a worldwide concern. During a large-scale outbreak, it is important that the public follows preventive advice. To increase compliance, insight in how the public gathers its knowledge and which factors determine whether or not an individual complies with preventive advice is crucial. METHODS: In 2012, contaminated salmon caused a large Salmonella Thompson outbreak in the Netherlands. During the outbreak, we conducted an online survey (n = 1,057) to assess the general public’s perceptions, knowledge, preventive behavior and sources of information. RESULTS: Respondents perceived Salmonella infections and the 2012 outbreak as severe (m = 4.21; five-point scale with 5 as severe). Their knowledge regarding common food sources, the incubation period and regular treatment of Salmonella (gastro-enteritis) was relatively low (e.g., only 28.7% knew that Salmonella is not normally treated with antibiotics). Preventive behavior differed widely, and the majority (64.7%) did not check for contaminated salmon at home. Most information about the outbreak was gathered through traditional media and news and newspaper websites. This was mostly determined by time spent on the medium. Social media played a marginal role. Wikipedia seemed a potentially important source of information. CONCLUSIONS: To persuade the public to take preventive actions, public health organizations should deliver their message primarily through mass media. Wikipedia seems a promising instrument for educating the public about food-borne Salmonella.",2014 Jan 31,"['van Velsen, Lex', 'Beaujean, Desirée JMA', 'van Gemert-Pijnen, Julia EWC', 'van Steenbergen, Jim E', 'Timen, Aura']",BMC Public Health,,,True
784c237bbdda9fbc087e1f42ce10e4948aa34a1b,PMC,Novel Bifunctional Single-Chain Variable Antibody Fragments to Enhance Virolysis by Complement: Generation and Proof-of-Concept,http://dx.doi.org/10.1155/2014/971345,PMC3913500,24524088,CC BY,"When bound to the envelope of viruses, factor H (FH), a soluble regulator of complement activation, contributes to the protection against a potent immune defense mechanism, the complement-mediated lysis (CML). Thus, removing FH from the surface renders viruses, such as HIV, susceptible to CML. For a proof of concept, we developed a construct consisting of recombinant bifunctional single-chain variable fragment (scFv) based on a monoclonal antibody against Friend murine leukemia virus (F-MuLV) envelope protein gp70, which was coupled to specific binding domains (short consensus repeats 19-20; SCR1920) of FH. We used Pichia pastoris as expression system in common shake flasks and optimized expression in high density bench top fermentation. Specific binding of recombinant scFv was proven by flow cytometry. The recombinant scFv-SCR significantly enhanced CML of F-MuLV in vitro implying that FH binding to the viral surface was impaired by the scFv-SCR. This novel concept to enhance virolysis may provide a new approach for antiviral treatment.",2014 Jan 12,"['Huber, Georg', 'Bánki, Zoltán', 'Kunert, Renate', 'Stoiber, Heribert']",Biomed Res Int,,,False
52431fafe4d5ccd27011d899aa54aa5aa3537e95,PMC,Novel Bifunctional Single-Chain Variable Antibody Fragments to Enhance Virolysis by Complement: Generation and Proof-of-Concept,http://dx.doi.org/10.1155/2014/971345,PMC3913500,24524088,CC BY,"When bound to the envelope of viruses, factor H (FH), a soluble regulator of complement activation, contributes to the protection against a potent immune defense mechanism, the complement-mediated lysis (CML). Thus, removing FH from the surface renders viruses, such as HIV, susceptible to CML. For a proof of concept, we developed a construct consisting of recombinant bifunctional single-chain variable fragment (scFv) based on a monoclonal antibody against Friend murine leukemia virus (F-MuLV) envelope protein gp70, which was coupled to specific binding domains (short consensus repeats 19-20; SCR1920) of FH. We used Pichia pastoris as expression system in common shake flasks and optimized expression in high density bench top fermentation. Specific binding of recombinant scFv was proven by flow cytometry. The recombinant scFv-SCR significantly enhanced CML of F-MuLV in vitro implying that FH binding to the viral surface was impaired by the scFv-SCR. This novel concept to enhance virolysis may provide a new approach for antiviral treatment.",2014 Jan 12,"['Huber, Georg', 'Bánki, Zoltán', 'Kunert, Renate', 'Stoiber, Heribert']",Biomed Res Int,,,True
8ecf2ad1996b1e93edd3eb7a8b2207114a33818a,PMC,Epidemiology of Multi-Drug Resistant Organisms in a Teaching Hospital in Oman: A One-Year Hospital-Based Study,http://dx.doi.org/10.1155/2014/157102,PMC3914445,24526881,CC BY,"Background. Antimicrobial resistance is increasingly recognized as a global challenge. A few studies have emerged on epidemiology of multidrug resistant organisms in tertiary care settings in the Arabian Gulf. Aim. To describe the epidemiology of multi-drug resistant organisms (MDRO) at Sultan Qaboos University Hospital, a tertiary hospital in Oman. Methods. A retrospective review of MDRO records has been conducted throughout the period from January 2012 till December 2012. Organisms were identified and tested by an automated identification and susceptibility system, and the antibiotic susceptibility testing was confirmed by the disk diffusion method. Results. Out of the total of 29,245 admissions, there have been 315 patients registered as MDRO patients giving an overall prevalence rate of 10.8 (95% CI 9.3, 12.4) MDRO cases per 1000 admissions. In addition, the prevalence rate of MDRO isolates was 11.2 (95% CI 9.7, 12.9) per 1000 admissions. Overall, increasing trends in prevalence rates of MDRO patients and MDRO isolates were observed throughout the study period. Conclusion. Antimicrobial resistance is an emerging challenge in Oman. Continuous monitoring of antimicrobial susceptibility and strict adherence to infection prevention guidelines are essential to prevent proliferation of MDRO. Along such quest, stringent antibiotic prescription guidelines are needed in the country.",2014 Jan 14,"['Balkhair, Abdullah', 'Al-Farsi, Yahya M.', 'Al-Muharrmi, Zakariya', 'Al-Rashdi, Raiya', 'Al-Jabri, Mansoor', 'Neilson, Fatma', 'Al-Adawi, Sara S.', 'El-Beeli, Marah', 'Al-Adawi, Samir']",ScientificWorldJournal,,,True
107824986103d1409f047ec9823d75b7b25d9702,PMC,Effect of the One-Child Policy on Influenza Transmission in China: A Stochastic Transmission Model,http://dx.doi.org/10.1371/journal.pone.0084961,PMC3916292,24516519,CC BY,"BACKGROUND: China's one-child-per-couple policy, introduced in 1979, led to profound demographic changes for nearly a quarter of the world's population. Several decades later, the consequences include decreased fertility rates, population aging, decreased household sizes, changes in family structure, and imbalanced sex ratios. The epidemiology of communicable diseases may have been affected by these changes since the transmission dynamics of infectious diseases depend on demographic characteristics of the population. Of particular interest is influenza because China and Southeast Asia lie at the center of a global transmission network of influenza. Moreover, changes in household structure may affect influenza transmission. Is it possible that the pronounced demographic changes that have occurred in China have affected influenza transmission? METHODS AND FINDINGS: To address this question, we developed a continuous-time, stochastic, individual-based simulation model for influenza transmission. With this model, we simulated 30 years of influenza transmission and compared influenza transmission rates in populations with and without the one-child policy control. We found that the average annual attack rate is reduced by 6.08% (SD 2.21%) in the presence of the one-child policy compared to a population in which no demographic changes occurred. There was no discernible difference in the secondary attack rate, −0.15% (SD 1.85%), between the populations with and without a one-child policy. We also forecasted influenza transmission over a ten-year time period in a population with a two-child policy under a hypothesis that a two-child-per-couple policy will be carried out in 2015, and found a negligible difference in the average annual attack rate compared to the population with the one-child policy. CONCLUSIONS: This study found that the average annual attack rate is slightly lowered in a population with a one-child policy, which may have resulted from a decrease in household size and the proportion of children in the population.",2014 Feb 6,"['Liu, Fengchen', 'Enanoria, Wayne T. A.', 'Ray, Kathryn J.', 'Coffee, Megan P.', 'Gordon, Aubree', 'Aragón, Tomás J.', 'Yu, Guowei', 'Cowling, Benjamin J.', 'Porco, Travis C.']",PLoS One,,,True
992365f92b227163487b5b2aa46063f842e7b36e,PMC,ABSL-4 Aerobiology Biosafety and Technology at the NIH/NIAID Integrated Research Facility at Fort Detrick,http://dx.doi.org/10.3390/v6010137,PMC3917435,24402304,CC BY,"The overall threat of a viral pathogen to human populations is largely determined by the modus operandi and velocity of the pathogen that is transmitted among humans. Microorganisms that can spread by aerosol are considered a more challenging enemy than those that require direct body-to-body contact for transmission, due to the potential for infection of numerous people rather than a single individual. Additionally, disease containment is much more difficult to achieve for aerosolized viral pathogens than for pathogens that spread solely via direct person-to-person contact. Thus, aerobiology has become an increasingly necessary component for studying viral pathogens that are naturally or intentionally transmitted by aerosol. The goal of studying aerosol viral pathogens is to improve public health preparedness and medical countermeasure development. Here, we provide a brief overview of the animal biosafety level 4 Aerobiology Core at the NIH/NIAID Integrated Research Facility at Fort Detrick, Maryland, USA.",2014 Jan 7,"['Lackemeyer, Matthew G.', 'de Kok-Mercado, Fabian', 'Wada, Jiro', 'Bollinger, Laura', 'Kindrachuk, Jason', 'Wahl-Jensen, Victoria', 'Kuhn, Jens H.', 'Jahrling, Peter B.']",Viruses,,,True
e8679d8c149ea6d25afb92e8a4f4b622dadcd872,PMC,Alveolar Macrophages Infected with Ames or Sterne Strain of Bacillus anthracis Elicit Differential Molecular Expression Patterns,http://dx.doi.org/10.1371/journal.pone.0087201,PMC3917846,24516547,CC0,"Alveolar macrophages (AMs) phagocytose Bacillus anthracis following inhalation and induce the production of pro-inflammatory cytokines and chemokines to mediate the activation of innate immunity. Ames, the virulent strain of B. anthracis, contains two plasmids that encode the antiphagocytic poly-γ-d-glutamic acid capsule and the lethal toxin. The attenuated Sterne strain of B. anthracis, which lacks the plasmid encoding capsule, is widely adapted as a vaccine strain. Although differences in the outcome of infection with the two strains may have originated from the presence or absence of an anti-phagocytic capsule, the disease pathogenesis following infection will be manifested via the host responses, which is not well understood. To gain understanding of the host responses at cellular level, a microarray analysis was performed using primary rhesus macaque AMs infected with either Ames or Sterne spores. Notably, 528 human orthologs were identified to be differentially expressed in AMs infected with either strain of the B. anthracis. Meta-analyses revealed genes differentially expressed in response to B. anthracis infection were also induced upon infections with multiple pathogens such as Francisella Novicida or Staphylococcus aureus. This suggests the existence of a common molecular signature in response to pathogen infections. Importantly, the microarray and protein expression data for certain cytokines, chemokines and host factors provide further insights on how cellular processes such as innate immune sensing pathways, anti-apoptosis versus apoptosis may be differentially modulated in response to the virulent or vaccine strain of B. anthracis. The reported differences may account for the marked difference in pathogenicity between these two strains.",2014 Feb 7,"['Langel, Felicia D.', 'Chiang, Chih-Yuan', 'Lane, Douglas', 'Kenny, Tara', 'Ojeda, Jenifer F.', 'Zhong, Yang', 'Che, Jianwei', 'Zhou, Yingyao', 'Ribot, Wilson', 'Kota, Krishna P.', 'Bavari, Sina', 'Panchal, Rekha G.']",PLoS One,,,True
b0da552a101206a82845a47dc3ee9f0a64ed2bac,PMC,"Respiratory viruses within homeless shelters in Marseille, France",http://dx.doi.org/10.1186/1756-0500-7-81,PMC3918144,24499605,CC BY,"BACKGROUND: Homeless shelters are identified as places where humans are at high risk of acquiring respiratory disease. We previously reported the prevalence of the main respiratory diseases affecting a population of homeless in Marseille, France. Here, we investigated the prevalence of 10 respiratory viruses in a similar homeless population during 2 successive winter seasons. FINDINGS: Following a clinical examination, we collected nasal specimens from which the RT-PCR detection of 10 respiratory viruses was performed through snapshot investigations. Among the 265 patients included, 150 (56.6%) reported at least one respiratory symptom of which 13 (8.7%) had positive swabs for at least one respiratory virus, and 115 patients reported any respiratory symptom of which 10 (8.7%) had positive swabs for respiratory virus. Overall, 23 patients had positive swabs for at least one respiratory virus. Human rhinovirus (HRV) was the predominant virus (13 isolates) followed by enteroviruses (3), human metapneumovirus (2), human coronavirus OC43 (2), 229E virus (2) and human respiratory syncytial virus subtype B (1). Among the patients infected with HRV, 10 were collected during the same snapshot. CONCLUSIONS: Although one half of the patients reported respiratory symptoms, the prevalence of respiratory viruses was within the range of that previously described in adult asymptomatic patients outside the homeless community. Most HRV-positive swabs were collected during the same snapshot suggesting a local outbreak. No influenza viruses were found despite the fact that one half of the patients were investigated during the peak of the seasonal influenza epidemic in Marseille.",2014 Feb 5,"['Thiberville, Simon-djamel', 'Salez, Nicolas', 'Benkouiten, Samir', 'Badiaga, Sekene', 'Charrel, Remi', 'Brouqui, Philippe']",BMC Res Notes,,,True
173ce92cbc6f228d5bfbdbd7ba7137523ebe36bd,PMC,Emergence of Enteric Viruses in Production Chickens Is a Concern for Avian Health,http://dx.doi.org/10.1155/2014/450423,PMC3919086,24578633,CC BY,"Several viruses have been identified in recent years in the intestinal contents of chickens and turkeys with enteric problems, which have been observed in commercial farms worldwide, including Brazil. Molecular detection of these viruses in Brazil can transform to a big threat for poultry production due to risk for intestinal integrity. This disease is characterized by severely delayed growth, low uniformity, lethargy, watery diarrhea, delayed feed consumption, and a decreased conversion rate. Chicken astrovirus (CAstV), rotavirus, reovirus, chicken parvovirus (ChPV), fowl adenovirus of subgroup I (FAdV-1), and avian nephritis virus (ANV) were investigated using the conventional polymerase chain reaction (PCR) and the reverse transcription polymerase chain reaction (RT-PCR). In addition, the infectious bronchitis virus (IBV), which may play a role in enteric disease, was included. The viruses most frequently detected, either alone or in concomitance with other viruses, were IBV, ANV, rotavirus, and CAstV followed by parvovirus, reovirus, and adenovirus. This study demonstrates the diversity of viruses in Brazilian chicken flocks presenting enteric problems characterized by diarrhea, growth retard, loss weight, and mortality, which reflects the multicausal etiology of this disease.",2014 Jan 22,"['Mettifogo, Elena', 'Nuñez, Luis F. N.', 'Chacón, Jorge L.', 'Santander Parra, Silvana H.', 'Astolfi-Ferreira, Claudete S.', 'Jerez, José A.', 'Jones, Richard C.', 'Piantino Ferreira, Antonio J.']",ScientificWorldJournal,,,True
1c5f2a7a584371461fa19a49e49c99ecd0ef7743,PMC,"Genetic Variability and Phylogeny of Current Chinese Porcine Epidemic Diarrhea Virus Strains Based on Spike, ORF3, and Membrane Genes",http://dx.doi.org/10.1155/2014/208439,PMC3919097,24578626,CC BY,"Since late 2010, the outbreak of porcine epidemic diarrhea (PED) in China has resulted in the deaths of millions of suckling piglets. The main cause of the disease outbreak was unknown. In this study, partial spike (S), ORF3, and membrane (M) genes amplified from these variants were sequenced and analyzed. The results showed that the variants could be clustered into one to three subgroups and suggested that S genes were variable, while M genes were relatively conserved. Moreover, in comparison with the vaccine strain CV777, sequence alignment analyses revealed that the S genes of the newly isolated strains contained several mutations at the aa level. It is possible that these mutations have changed the hydrophobicity of the S protein and influenced the viral antigenicity and virulence. Interestingly, homology analyses based on ORF3 demonstrated that the isolates had an intact opening reading frame (ORF), which were different from the attenuated DR13 strain. In conclusion, the widespread PED virus (PEDV) isolates had virulent characteristics. Additionally, the high degree of variation in the genes, particularly S genes, might provide an explanation for the poor immunity and rapid spread of the disease.",2014 Jan 22,"['Sun, Ruiqin', 'Leng, Zhangming', 'Zhai, Shao-Lun', 'Chen, Dekun', 'Song, Changxu']",ScientificWorldJournal,,,True
66daba9fe4360f00714bd778402b6ac3489b2ec6,PMC,Stimulation of ribosomal frameshifting by RNA G-quadruplex structures,http://dx.doi.org/10.1093/nar/gkt1022,PMC3919603,24178029,CC BY,"Guanine-rich sequences can fold into four-stranded structures of stacked guanine-tetrads, so-called G-quadruplexes (G4). These unique motifs have been extensively studied on the DNA level; however, exploration of the biological roles of G4s at the RNA level is just emerging. Here we show that G4 RNA when introduced within coding regions are capable of stimulating −1 ribosomal frameshifting (−1 FS) in vitro and in cultured cells. Systematic manipulation of the loop length between each G-tract revealed that the −1 FS efficiency positively correlates with G4 stability. Addition of a G4-stabilizing ligand, PhenDC3, resulted in higher −1 FS. Further, we demonstrated that the G4s can stimulate +1 FS and stop codon readthrough as well. These results suggest a potentially novel translational gene regulation mechanism mediated by G4 RNA.",2014 Feb 30,"['Yu, Chien-Hung', 'Teulade-Fichou, Marie-Paule', 'Olsthoorn, René C. L.']",Nucleic Acids Res,,,True
cada5b298ac838d0b1414918d4c0eba698ee7276,PMC,Stimulation of ribosomal frameshifting by RNA G-quadruplex structures,http://dx.doi.org/10.1093/nar/gkt1022,PMC3919603,24178029,CC BY,"Guanine-rich sequences can fold into four-stranded structures of stacked guanine-tetrads, so-called G-quadruplexes (G4). These unique motifs have been extensively studied on the DNA level; however, exploration of the biological roles of G4s at the RNA level is just emerging. Here we show that G4 RNA when introduced within coding regions are capable of stimulating −1 ribosomal frameshifting (−1 FS) in vitro and in cultured cells. Systematic manipulation of the loop length between each G-tract revealed that the −1 FS efficiency positively correlates with G4 stability. Addition of a G4-stabilizing ligand, PhenDC3, resulted in higher −1 FS. Further, we demonstrated that the G4s can stimulate +1 FS and stop codon readthrough as well. These results suggest a potentially novel translational gene regulation mechanism mediated by G4 RNA.",2014 Feb 30,"['Yu, Chien-Hung', 'Teulade-Fichou, Marie-Paule', 'Olsthoorn, René C. L.']",Nucleic Acids Res,,,False
3e01904917aea1c46193a3e98307e95be703c7c6,PMC,Cyclophilin A: a key player for human disease,http://dx.doi.org/10.1038/cddis.2013.410,PMC3920964,24176846,CC BY,"Cyclophilin A (CyPA) is a ubiquitously distributed protein belonging to the immunophilin family. CyPA has peptidyl prolyl cis-trans isomerase (PPIase) activity, which regulates protein folding and trafficking. Although CyPA was initially believed to function primarily as an intracellular protein, recent studies have revealed that it can be secreted by cells in response to inflammatory stimuli. Current research in animal models and humans has provided compelling evidences supporting the critical function of CyPA in several human diseases. This review discusses recently available data about CyPA in cardiovascular diseases, viral infections, neurodegeneration, cancer, rheumatoid arthritis, sepsis, asthma, periodontitis and aging. It is believed that further elucidations of the role of CyPA will provide a better understanding of the molecular mechanisms underlying these diseases and will help develop novel pharmacological therapies.",2013 Oct 31,"['Nigro, P', 'Pompilio, G', 'Capogrossi, M C']",Cell Death Dis,,,True
1c995ac4ae70bbcc5da53211e20df4398d1ce55d,PMC,"Autophagic response in the Rabbit Hemorrhagic Disease, an animal model of virally-induced fulminant hepatic failure",http://dx.doi.org/10.1186/1297-9716-45-15,PMC3922607,24490870,CC BY,"The Rabbit Hemorrhagic Disease Virus (RHDV) induces a severe disease that fulfils many requirements of an animal model of fulminant hepatic failure. However, a better knowledge of molecular mechanisms contributing to liver damage is required, and it is unknown whether the RHDV induces liver autophagy and how it relates to apoptosis. In this study, we attempted to explore which signalling pathways were involved in the autophagic response induced by the RHDV and to characterize their role in the context of RHDV pathogenesis. Rabbits were infected with 2 × 10(4) hemmaglutination units of a RHDV isolate. The autophagic response was measured as presence of autophagic vesicles, LC3 staining, conversion of LC3-I to autophagosome-associated LC3-II and changes in expression of beclin-1, UVRAG, Atg5, Atg12, Atg16L1 and p62/SQSTM1. RHDV-triggered autophagy reached a maximum at 24 hours post-infection (hpi) and declined at 30 and 36 hpi. Phosphorylation of mTOR also augmented in early periods of infection and there was an increase in the expression of the endoplasmic reticulum chaperones BiP/GRP78, CHOP and GRP94. Apoptosis, measured as caspase-3 activity and expression of PARP-1, increased significantly at 30 and 36 hpi in parallel to the maximal expression of the RHDV capsid protein VP60. These data indicate that RHDV infection initiates a rapid autophagic response, perhaps in an attempt to protect liver, which associates to ER stress development and is independent from downregulation of the major autophagy suppressor mTOR. As the infection continues and the autophagic response declines, cells begin to exhibit apoptosis.",2014 Feb 4,"['Vallejo, Daniela', 'Crespo, Irene', 'San-Miguel, Beatriz', 'Álvarez, Marcelino', 'Prieto, Jesús', 'Tuñón, María Jesús', 'González-Gallego, Javier']",Vet Res,,,True
58f9cce5d568b8cc7c7eb62a3b03b476a5ced52d,PMC,"Animal Viruses, Bacteria, and Cancer: A Brief Commentary",http://dx.doi.org/10.3389/fpubh.2014.00014,PMC3923154,24592380,CC BY,"Animal viruses and bacteria are ubiquitous in the environment. However, little is known about their mode of transmission and etiologic role in human cancers, especially among high-risk groups (e.g., farmers, veterinarians, poultry plant workers, pet owners, and infants). Many factors may affect the survival, transmissibility, and carcinogenicity of these agents, depending on the animal-host environment, hygiene practices, climate, travel, herd immunity, and cultural differences in food consumption and preparation. Seasonal variations in immune function also may increase host susceptibility at certain times of the year. The lack of objective measures, inconsistent study designs, and sources of epidemiologic bias (e.g., residual confounding, recall bias, and non-randomized patient selection) are some of the factors that complicate a clear understanding of this subject.",2014 Feb 13,"['Efird, Jimmy T.', 'Davies, Stephen W.', 'O’Neal, Wesley T.', 'Anderson, Ethan J.']",Front Public Health,,,True
074b685a347c109752be7efe757c3985190ec6c4,PMC,"Vaccine Effectiveness against Medically Attended Laboratory-Confirmed Influenza in Japan, 2011–2012 Season",http://dx.doi.org/10.1371/journal.pone.0088813,PMC3923823,24551167,CC BY,"The objective of this study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza during the 2011–2012 season in Japan using a test-negative case-control study design. The effect of co-circulating non-influenza respiratory viruses (NIRVs) on VE estimates was also explored. Nasopharyngeal swab samples were collected from outpatients with influenza-like illnesses (ILIs) in a community hospital in Nagasaki, Japan. Thirteen respiratory viruses (RVs), including influenza A and B, were identified from the samples using a multiplex polymerase chain reaction. The difference in VE point estimates was assessed using three different controls: ILI patients that tested negative for influenza, those that tested negative for all RVs, and those that tested positive for NIRVs. The adjusted VE against medically attended, laboratory-confirmed influenza using all influenza-negative controls was 5.3% (95% confidence interval [CI], −60.5 to 44.1). The adjusted VEs using RV-negative and NIRV-positive controls were −1.5% (95% CI, −74.7 to 41) and 50% (95% CI, −43.2 to 82.5), respectively. Influenza VE was limited in Japan during the 2011–2012 season. Although the evidence is not conclusive, co-circulating NIRVs may affect influenza VE estimates in test-negative case-control studies.",2014 Feb 13,"['Suzuki, Motoi', 'Minh, Le Nhat', 'Yoshimine, Hiroyuki', 'Inoue, Kenichiro', 'Yoshida, Lay Myint', 'Morimoto, Konosuke', 'Ariyoshi, Koya']",PLoS One,,,True
2000b147cb90354ba98206dffbc47deddddcc84d,PMC,Utilization of and Direct Expenditure for Emergency Medical 
Care in Taiwan: A Population-based Descriptive Study,http://dx.doi.org/10.2188/jea.JE20080042,PMC3924095,19164870,CC BY,"BACKGROUND: We surveyed the emergency medical system (EMS) in Taiwan to provide information to policymakers responsible for decisions regarding the redistribution of national medical resources. METHODS: A systematic sampling method was used to randomly sample a representative database from the National Health Insurance (NHI) database in Taiwan, during the period from 2000 to 2004. RESULTS: We identified 10,124, 10,408, 11,209, 10,686, and 11,914 emergency room visits in 2000, 2001, 2002, 2003, and 2004, respectively. There were more males than females, and the majority of adults were younger than 50 years. Diagnose of injury/poisoning was the most frequently noted diagnostic category in emergency departments (EDs) in Taiwan. There were 13,196 (24.3%) and 2,952 (5.4%) patients with 2 and 3 concomitant diagnoses, respectively. There was a significant association between advanced age and the existence of multiple diagnoses (P < 0.001). With the exception of the ill-defined symptoms/signs/conditions, the two most frequent diagnoses were diseases of the circulatory system and diseases of the respiratory system in patients aged 65 years or older. On average, treatment-associated expenditure and drug-associated expenditure in Taiwan EDs averaged NT$1,155 ($35.0) and NT$190 ($5.8), respectively, which was equal to 64.5% and 10.6% of the total ED-associated cost. General ED medical expenditure increased with patient age; the increased cost ratio due to age was estimated at 8% per year (P < 0.001). CONCLUSIONS: The frequency of major health problems diagnosed at ED visits varied by age: more complicated complaints and multiple diagnoses were more frequent in older patients. In Taiwan, the ED system remains overloaded, possibly because of the low cost of an ED visit.",2009 Jan 30,"['Yang, Nan-Ping', 'Lee, Yi-Hui', 'Lin, Ching-Heng', 'Chung, Yuan-Chang', 'Chen, Wen-Jone', 'Chou, Pesus']",J Epidemiol,,,True
6ff529e1f29ef13037ef1117086082db53d12691,PMC,Support vector machine (SVM) based multiclass prediction with basic statistical analysis of plasminogen activators,http://dx.doi.org/10.1186/1756-0500-7-63,PMC3924408,24468032,CC BY,"BACKGROUND: Plasminogen (Pg), the precursor of the proteolytic and fibrinolytic enzyme of blood, is converted to the active enzyme plasmin (Pm) by different plasminogen activators (tissue plasminogen activators and urokinase), including the bacterial activators streptokinase and staphylokinase, which activate Pg to Pm and thus are used clinically for thrombolysis. The identification of Pg-activators is therefore an important step in understanding their functional mechanism and derives new therapies. METHODS: In this study, different computational methods for predicting plasminogen activator peptide sequences with high accuracy were investigated, including support vector machines (SVM) based on amino acid (AC), dipeptide composition (DC), PSSM profile and Hybrid methods used to predict different Pg-activators from both prokaryotic and eukaryotic origins. RESULTS: Overall maximum accuracy, evaluated using the five-fold cross validation technique, was 88.37%, 84.32%, 87.61%, 85.63% in 0.87, 0.83,0.86 and 0.85 MCC with amino (AC) or dipeptide composition (DC), PSSM profile and Hybrid methods respectively. Through this study, we have found that the different subfamilies of Pg-activators are quite closely correlated in terms of amino, dipeptide, PSSM and Hybrid compositions. Therefore, our prediction results show that plasminogen activators are predictable with a high accuracy from their primary sequence. Prediction performance was also cross-checked by confusion matrix and ROC (Receiver operating characteristics) analysis. A web server to facilitate the prediction of Pg-activators from primary sequence data was implemented. CONCLUSION: The results show that dipeptide, PSSM profile, and Hybrid based methods perform better than single amino acid composition (AC). Furthermore, we also have developed a web server, which predicts the Pg-activators and their classification (available online at http://mamsap.it.deakin.edu.au/plas_pred/home.html). Our experimental results show that our approaches are faster and achieve generally a good prediction performance.",2014 Jan 27,"['Muthukrishnan, Selvaraj', 'Puri, Munish', 'Lefevre, Christophe']",BMC Res Notes,,,True
1fdefb8aa4368ef11e32bad469c37591b0eb24bc,PMC,Recent developments in antiviral agents against enterovirus 71 infection,http://dx.doi.org/10.1186/1423-0127-21-14,PMC3924904,24521134,CC BY,"Enterovirus 71 (EV-71) is the main etiological agent of hand, foot and mouth disease (HFMD). Recent EV-71 outbreaks in Asia-Pacific were not limited to mild HFMD, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death. The absence of licensed therapeutics for clinical use has intensified research into anti-EV-71 development. This review highlights the potential antiviral agents targeting EV-71 attachment, entry, uncoating, translation, polyprotein processing, virus-induced formation of membranous RNA replication complexes, and RNA-dependent RNA polymerase. The strategies for antiviral development include target-based synthetic compounds, anti-rhinovirus and poliovirus libraries screening, and natural compound libraries screening. Growing knowledge of the EV-71 life cycle will lead to successful development of antivirals. The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine. The coupling of antivirals with an effective vaccine will accelerate eradication of the disease.",2014 Feb 12,"['Tan, Chee Wah', 'Lai, Jeffrey Kam Fatt', 'Sam, I-Ching', 'Chan, Yoke Fun']",J Biomed Sci,,,True
dc38fa3321df5137294140ffe1a358399befb500,PMC,Distinct Immune Response in Two MERS-CoV-Infected Patients: Can We Go from Bench to Bedside?,http://dx.doi.org/10.1371/journal.pone.0088716,PMC3925152,24551142,CC BY,"One year after the occurrence of the first case of infection by the Middle East Respiratory Syndrome coronavirus (MERS-CoV) there is no clear consensus on the best treatment to propose. The World Health Organization, as well as several other national agencies, are still working on different clinical approaches to implement the most relevant treatment in MERS-CoV infection. We compared innate and adaptive immune responses of two patients infected with MERS-CoV to understand the underlying mechanisms involved in the response and propose potential therapeutic approaches. Broncho-alveolar lavage (BAL) of the first week and sera of the first month from the two patients were used in this study. Quantitative polymerase chain reaction (qRTPCR) was performed after extraction of RNA from BAL cells of MERS-CoV infected patients and control patients. BAL supernatants and sera were used to assess cytokines and chemokines secretion by enzyme-linked immunosorbent assay. The first patient died rapidly after 3 weeks in the intensive care unit, the second patient still recovers from infection. The patient with a poor outcome (patient 1), compared to patient 2, did not promote type-1 Interferon (IFN), and particularly IFNα, in response to double stranded RNA (dsRNA) from MERS-CoV. The absence of IFNα, known to promote antigen presentation in response to viruses, impairs the development of a robust antiviral adaptive Th-1 immune response. This response is mediated by IL-12 and IFNγ that decreases viral clearance; levels of both of these mediators were decreased in patient 1. Finally, we confirm previous in vitro findings that MERS-CoV can drive IL-17 production in humans. Host recognition of viral dsRNA determines outcome in the early stage of MERS-CoV infection. We highlight the critical role of IFNα in this initial stage to orchestrate a robust immune response and bring substantial arguments for the indication of early IFNα treatment during MERS-CoV infection.",2014 Feb 14,"['Faure, Emmanuel', 'Poissy, Julien', 'Goffard, Anne', 'Fournier, Clement', 'Kipnis, Eric', 'Titecat, Marie', 'Bortolotti, Perinne', 'Martinez, Laura', 'Dubucquoi, Sylvain', 'Dessein, Rodrigue', 'Gosset, Philippe', 'Mathieu, Daniel', 'Guery, Benoit']",PLoS One,,,True
439ddbbdb17f5ab18ac2e208e7df5c09a8dc9789,PMC,Unexplained diarrhoea in HIV-1 infected individuals,http://dx.doi.org/10.1186/1471-2334-14-22,PMC3925291,24410947,CC BY,"BACKGROUND: Gastrointestinal symptoms, in particular diarrhoea, are common in non-treated HIV-1 infected individuals. Although various enteric pathogens have been implicated, the aetiology of diarrhoea remains unexplained in a large proportion of HIV-1 infected patients. Our aim is to identify the cause of diarrhoea for patients that remain negative in routine diagnostics. METHODS: In this study stool samples of 196 HIV-1 infected persons, including 29 persons with diarrhoea, were examined for enteropathogens and HIV-1. A search for unknown and unexpected viruses was performed using virus discovery cDNA-AFLP combined with Roche-454 sequencing (VIDISCA-454). RESULTS: HIV-1 RNA was detected in stool of 19 patients with diarrhoea (66%) compared to 75 patients (45%) without diarrhoea. In 19 of the 29 diarrhoea cases a known enteropathogen could be identified (66%). Next to these known causative agents, a range of recently identified viruses was identified via VIDISCA-454: cosavirus, Aichi virus, human gyrovirus, and non-A non-B hepatitis virus. Moreover, a novel virus was detected which was named immunodeficiency-associated stool virus (IASvirus). However, PCR based screening for these viruses showed that none of these novel viruses was associated with diarrhoea. Notably, among the 34% enteropathogen-negative cases, HIV-1 RNA shedding in stool was more frequently observed (80%) compared to enteropathogen-positive cases (47%), indicating that HIV-1 itself is the most likely candidate to be involved in diarrhoea. CONCLUSION: Unexplained diarrhoea in HIV-1 infected patients is probably not caused by recently described or previously unknown pathogens, but it is more likely that HIV-1 itself plays a role in intestinal mucosal abnormalities which leads to diarrhoea.",2014 Jan 13,"['Oude Munnink, Bas B', 'Canuti, Marta', 'Deijs, Martin', 'de Vries, Michel', 'Jebbink, Maarten F', 'Rebers, Sjoerd', 'Molenkamp, Richard', 'van Hemert, Formijn J', 'Chung, Kevin', 'Cotten, Matthew', 'Snijders, Fransje', 'Sol, Cees JA', 'van der Hoek, Lia']",BMC Infect Dis,,,True
386c21f11ae0c9199c26218e334373932f3fa0c0,PMC,Profile of international air passengers intercepted with illegal animal products in baggage at Guarulhos and Galeão airports in Brazil,http://dx.doi.org/10.1186/2193-1801-3-69,PMC3925492,24567878,CC BY,"Protection against biological material entering a country or region through airports is important because, through them, infectious agents can quickly reach exotic destinations and be disseminated. Illegal products of animal origin may contain hazardous infectious agents that can compromise animal and public health. The aim of this study was to identify associations between possession of illegal animal products in baggage and demographic characteristics of the passengers, as well as characteristics of their travel plans in the two main Brazilian international airports. A total of 457 passengers were divided into two groups: passengers identified as carrying illegal animal products and control. Passengers identified as carrying illegal animal products not stated on the accompanied baggage declaration completed a questionnaire, to aid in profiling. Nationality, origin, age and residency of passengers were analyzed using chi square, logistic regression and odds ratios. Passengers from Eastern Europe were the most likely to enter with animal products as were those aged between 35 and 55 years. When evaluating the departure point, the highest frequency was seen in those coming from Portugal. Passenger group, reasons for travel, amount and type of baggage were available only for passengers identified as carrying illegal animal products, noting that they prefer traveling alone, for leisure, bringing few bags. Such information can contribute to the early identification of passengers that have illegal animal products in baggage at Brazilian airports.",2014 Feb 6,"['de Melo, Cristiano Barros', 'Pinheiro de Sá, Marcos Eielson', 'Alves, Flaviane Faria', 'McManus, Concepta', 'Aragão, Lucas Fernandes', 'Belo, Bruno Benin', 'Campani, Paulo Ricardo', 'da Matta Ribeiro, Antonio Cavalcanti', 'Seabra, Christina Isoldi', 'Seixas, Luiza']",Springerplus,,,True
a792bbaa94e64b3e7e230718d114dfd5d8d174dd,PMC,Global health in the European Union – a review from an agenda-setting perspective,http://dx.doi.org/10.3402/gha.v7.23610,PMC3925807,24560264,CC BY,"This review attempts to analyse the global health agenda-setting process in the European Union (EU). We give an overview of the European perspective on global health, making reference to the developments that led to the EU acknowledging its role as a global health actor. The article thereby focusses in particular on the European interpretation of its role in global health from 2010, which was formalised through, respectively, a European Commission Communication and European Council Conclusions. Departing from there, and based on Kingdon's multiple streams theory on agenda setting, we identify some barriers that seem to hinder the further establishment and promotion of a solid global health agenda in the EU. The main barriers for creating a strong European global health agenda are the fragmentation of the policy community and the lack of a common definition for global health in Europe. Forwarding the agenda in Europe for global health requires more clarification of the common goals and perspectives of the policy community and the use of arising windows of opportunity.",2014 Feb 13,"['Aluttis, Christoph', 'Krafft, Thomas', 'Brand, Helmut']",Glob Health Action,,,True
0be7b06a39aa31b27514a501ebdd477f42b0919a,PMC,Antifragility and Tinkering in Biology (and in Business) Flexibility Provides an Efficient Epigenetic Way to Manage Risk,http://dx.doi.org/10.3390/genes2040998,PMC3927596,24710302,CC BY,"The notion of antifragility, an attribute of systems that makes them thrive under variable conditions, has recently been proposed by Nassim Taleb in a business context. This idea requires the ability of such systems to ‘tinker’, i.e., to creatively respond to changes in their environment. A fairly obvious example of this is natural selection-driven evolution. In this ubiquitous process, an original entity, challenged by an ever-changing environment, creates variants that evolve into novel entities. Analyzing functions that are essential during stationary-state life yield examples of entities that may be antifragile. One such example is proteins with flexible regions that can undergo functional alteration of their side residues or backbone and thus implement the tinkering that leads to antifragility. This in-built property of the cell chassis must be taken into account when considering construction of cell factories driven by engineering principles.",2011 Nov 29,"['Danchin, Antoine', 'Binder, Philippe M.', 'Noria, Stanislas']",Genes (Basel),,,True
6a2386de99a966c8755732f196ba4c2cc0dda2f2,PMC,Selection of Suitable Reference Genes for Normalization of Quantitative Real-Time Polymerase Chain Reaction in Human Cartilage Endplate of the Lumbar Spine,http://dx.doi.org/10.1371/journal.pone.0088892,PMC3928306,24558443,CC BY,"The quantitative real-time polymerase chain reaction (qRT-PCR) is one of the most widely used methods to study gene expression profiles, and it requires appropriate normalization for accurate and reliable results. Although several genes are commonly used as reference genes (such as GAPDH, ACTB, and 18S rRNA), they are also regulated and can be expressed at varying levels. In this study, we evaluated twelve well-known reference genes to identify the most suitable housekeeping gene for normalization of qRT-PCR in human lumbar vertebral endplate with Modic changes, by using the geNorm, NormFinder, and BestKeeper algorithms. Our results showed that the rarely-used SDHA was the most stable single reference gene, and a combination of three, SDHA, B2M, and LDHA, was the most suitable gene set for normalization in all samples. In addition, the commonly-used genes, GAPDH, ACTB and 18S rRNA, were all inappropriate as internal standards. The rankings of reference genes for the three types of Modic change differed, although SDHA and RPL13A uniformly ranked in the first and last position, respectively. Further simulated expression analysis validated that the arbitrary use of a reference gene could lead to the misinterpretation of data. Our study confirmed the necessity of exploring the expression stability of potential reference genes in each specific tissue and experimental situation before quantitative evaluation of gene expression by qRT-PCR.",2014 Feb 18,"['Zhou, Zhi-Jie', 'Zhang, Jian-Feng', 'Xia, Ping', 'Wang, Ji-Ying', 'Chen, Shuai', 'Fang, Xiang-Qian', 'Fan, Shun-Wu']",PLoS One,,,True
a7ab989eb31d8d6dd0a09da2ee0cf5f6a5182885,PMC,Zoonoses and One Health: A Review of the Literature,http://dx.doi.org/10.1155/2014/874345,PMC3928857,24634782,CC BY,"Background. One health is a concept that was officially adopted by international organizations and scholarly bodies in 1984. It is the notion of combining human, animal, and environmental components to address global health challenges that have an ecological interconnectedness. Methods. A cross-sectional study of the available literature cited was conducted from January 1984 when the one health concept was adopted till December 2012 to examine the role of the one health approach towards zoonoses. Inclusion criteria included publications, professional presentations, funding allocations, official documentation books, and book chapters, and exclusion criteria included those citations written outside the period of review. Results. A total of 737 resources met the inclusion criteria and were considered in this review. Resources showed a continuous upward trend for the years from 2006 to 2012. The predominant resources were journal publications with environmental health as the significant scope focus for one health. There was also an emphasis on the distribution of the work from developed countries. All categories of years, resources, scopes, and country locale differed from the means (P = 0.000). Year of initiative, scope, and country locale showed a dependent relationship (P = 0.022, P = 0.003, and P = 0.021, resp.). Conclusion. Our findings demonstrate the rapid growth in embracing the concept of one health, particularly in developed countries over the past six years. The advantages and benefits of this approach in tackling zoonoses are manifold, yet they are still not seemingly being embraced in developing countries where zoonoses have the greatest impact.",2014 Jan 30,"['Bidaisee, Satesh', 'Macpherson, Calum N. L.']",J Parasitol Res,,,True
ade1a8f088544b34547d3f9608805c969c9f189f,PMC,"The General Composition of the Faecal Virome of Pigs Depends on Age, but Not on Feeding with a Probiotic Bacterium",http://dx.doi.org/10.1371/journal.pone.0088888,PMC3929612,24586429,CC BY,"BACKGROUND: The pig faecal virome, which comprises the community of viruses present in pig faeces, is complex and consists of pig viruses, bacteriophages, transiently passaged plant viruses and other minor virus species. Only little is known about factors influencing its general composition. Here, the effect of the probiotic bacterium Enterococcus faecium (E. faecium) NCIMB 10415 on the pig faecal virome composition was analysed in a pig feeding trial with sows and their piglets, which received either the probiotic bacterium or not. RESULTS: From 8 pooled faecal samples derived from the feeding trial, DNA and RNA virus particles were prepared and subjected to process-controlled Next Generation Sequencing resulting in 390,650 sequence reads. In average, 14% of the reads showed significant sequence identities to known viruses. The percentage of detected mammalian virus sequences was highest (55–77%) in the samples of the youngest piglets and lowest (8–10%) in the samples of the sows. In contrast, the percentage of bacteriophage sequences increased from 22–44% in the youngest piglets to approximately 90% in the sows. The dominating mammalian viruses differed remarkably among 12 day-old piglets (kobuvirus), 54 day-old piglets (boca-, dependo- and pig stool-associated small circular DNA virus [PigSCV]) and the sows (PigSCV, circovirus and “circovirus-like” viruses CB-A and RW-A). In addition, the Shannon index, which reflects the diversity of sequences present in a sample, was generally higher for the sows as compared to the piglets. No consistent differences in the virome composition could be identified between the viromes of the probiotic bacterium-treated group and the control group. CONCLUSION: The analysis indicates that the pig faecal virome shows a high variability and that its general composition is mainly dependent on the age of the pigs. Changes caused by feeding with the probiotic bacterium E. faecium could not be demonstrated using the applied metagenomics method.",2014 Feb 19,"['Sachsenröder, Jana', 'Twardziok, Sven O.', 'Scheuch, Matthias', 'Johne, Reimar']",PLoS One,,,True
f3160710f61d4812ee7b310d0966c3d48ca30d28,PMC,"The General Composition of the Faecal Virome of Pigs Depends on Age, but Not on Feeding with a Probiotic Bacterium",http://dx.doi.org/10.1371/journal.pone.0088888,PMC3929612,24586429,CC BY,"BACKGROUND: The pig faecal virome, which comprises the community of viruses present in pig faeces, is complex and consists of pig viruses, bacteriophages, transiently passaged plant viruses and other minor virus species. Only little is known about factors influencing its general composition. Here, the effect of the probiotic bacterium Enterococcus faecium (E. faecium) NCIMB 10415 on the pig faecal virome composition was analysed in a pig feeding trial with sows and their piglets, which received either the probiotic bacterium or not. RESULTS: From 8 pooled faecal samples derived from the feeding trial, DNA and RNA virus particles were prepared and subjected to process-controlled Next Generation Sequencing resulting in 390,650 sequence reads. In average, 14% of the reads showed significant sequence identities to known viruses. The percentage of detected mammalian virus sequences was highest (55–77%) in the samples of the youngest piglets and lowest (8–10%) in the samples of the sows. In contrast, the percentage of bacteriophage sequences increased from 22–44% in the youngest piglets to approximately 90% in the sows. The dominating mammalian viruses differed remarkably among 12 day-old piglets (kobuvirus), 54 day-old piglets (boca-, dependo- and pig stool-associated small circular DNA virus [PigSCV]) and the sows (PigSCV, circovirus and “circovirus-like” viruses CB-A and RW-A). In addition, the Shannon index, which reflects the diversity of sequences present in a sample, was generally higher for the sows as compared to the piglets. No consistent differences in the virome composition could be identified between the viromes of the probiotic bacterium-treated group and the control group. CONCLUSION: The analysis indicates that the pig faecal virome shows a high variability and that its general composition is mainly dependent on the age of the pigs. Changes caused by feeding with the probiotic bacterium E. faecium could not be demonstrated using the applied metagenomics method.",2014 Feb 19,"['Sachsenröder, Jana', 'Twardziok, Sven O.', 'Scheuch, Matthias', 'Johne, Reimar']",PLoS One,,,False
490ce7b2903c51796088daeeaeac576e76eabcc9,PMC,"The General Composition of the Faecal Virome of Pigs Depends on Age, but Not on Feeding with a Probiotic Bacterium",http://dx.doi.org/10.1371/journal.pone.0088888,PMC3929612,24586429,CC BY,"BACKGROUND: The pig faecal virome, which comprises the community of viruses present in pig faeces, is complex and consists of pig viruses, bacteriophages, transiently passaged plant viruses and other minor virus species. Only little is known about factors influencing its general composition. Here, the effect of the probiotic bacterium Enterococcus faecium (E. faecium) NCIMB 10415 on the pig faecal virome composition was analysed in a pig feeding trial with sows and their piglets, which received either the probiotic bacterium or not. RESULTS: From 8 pooled faecal samples derived from the feeding trial, DNA and RNA virus particles were prepared and subjected to process-controlled Next Generation Sequencing resulting in 390,650 sequence reads. In average, 14% of the reads showed significant sequence identities to known viruses. The percentage of detected mammalian virus sequences was highest (55–77%) in the samples of the youngest piglets and lowest (8–10%) in the samples of the sows. In contrast, the percentage of bacteriophage sequences increased from 22–44% in the youngest piglets to approximately 90% in the sows. The dominating mammalian viruses differed remarkably among 12 day-old piglets (kobuvirus), 54 day-old piglets (boca-, dependo- and pig stool-associated small circular DNA virus [PigSCV]) and the sows (PigSCV, circovirus and “circovirus-like” viruses CB-A and RW-A). In addition, the Shannon index, which reflects the diversity of sequences present in a sample, was generally higher for the sows as compared to the piglets. No consistent differences in the virome composition could be identified between the viromes of the probiotic bacterium-treated group and the control group. CONCLUSION: The analysis indicates that the pig faecal virome shows a high variability and that its general composition is mainly dependent on the age of the pigs. Changes caused by feeding with the probiotic bacterium E. faecium could not be demonstrated using the applied metagenomics method.",2014 Feb 19,"['Sachsenröder, Jana', 'Twardziok, Sven O.', 'Scheuch, Matthias', 'Johne, Reimar']",PLoS One,,,False
43773723e483187647685be053b62f601a8d91d3,PMC,"The General Composition of the Faecal Virome of Pigs Depends on Age, but Not on Feeding with a Probiotic Bacterium",http://dx.doi.org/10.1371/journal.pone.0088888,PMC3929612,24586429,CC BY,"BACKGROUND: The pig faecal virome, which comprises the community of viruses present in pig faeces, is complex and consists of pig viruses, bacteriophages, transiently passaged plant viruses and other minor virus species. Only little is known about factors influencing its general composition. Here, the effect of the probiotic bacterium Enterococcus faecium (E. faecium) NCIMB 10415 on the pig faecal virome composition was analysed in a pig feeding trial with sows and their piglets, which received either the probiotic bacterium or not. RESULTS: From 8 pooled faecal samples derived from the feeding trial, DNA and RNA virus particles were prepared and subjected to process-controlled Next Generation Sequencing resulting in 390,650 sequence reads. In average, 14% of the reads showed significant sequence identities to known viruses. The percentage of detected mammalian virus sequences was highest (55–77%) in the samples of the youngest piglets and lowest (8–10%) in the samples of the sows. In contrast, the percentage of bacteriophage sequences increased from 22–44% in the youngest piglets to approximately 90% in the sows. The dominating mammalian viruses differed remarkably among 12 day-old piglets (kobuvirus), 54 day-old piglets (boca-, dependo- and pig stool-associated small circular DNA virus [PigSCV]) and the sows (PigSCV, circovirus and “circovirus-like” viruses CB-A and RW-A). In addition, the Shannon index, which reflects the diversity of sequences present in a sample, was generally higher for the sows as compared to the piglets. No consistent differences in the virome composition could be identified between the viromes of the probiotic bacterium-treated group and the control group. CONCLUSION: The analysis indicates that the pig faecal virome shows a high variability and that its general composition is mainly dependent on the age of the pigs. Changes caused by feeding with the probiotic bacterium E. faecium could not be demonstrated using the applied metagenomics method.",2014 Feb 19,"['Sachsenröder, Jana', 'Twardziok, Sven O.', 'Scheuch, Matthias', 'Johne, Reimar']",PLoS One,,,False
5926e0775494fcad788d2e93e3a5ddac4d5aeb0d,PMC,Infrastructure and Contamination of the Physical Environment in Three Bangladeshi Hospitals: Putting Infection Control into Context,http://dx.doi.org/10.1371/journal.pone.0089085,PMC3929649,24586516,CC0,"OBJECTIVE: This paper describes the physical structure and environmental contamination in selected hospital wards in three government hospitals in Bangladesh. METHODS: The qualitative research team conducted 48 hours of observation in six wards from three Bangladeshi tertiary hospitals in 2007. They recorded environmental contamination with body secretions and excretions and medical waste and observed ward occupant handwashing and use of personal protective equipment. They recorded number of persons, number of open doors and windows, and use of fans. They measured the ward area and informally observed waste disposal outside the wards. They conducted nine focus group discussions with doctors, nurses and support staff. RESULTS: A median of 3.7 persons were present per 10 m(2) of floor space in the wards. A median of 4.9 uncovered coughs or sneezes were recorded per 10 m(2) per hour per ward. Floors in the wards were soiled with saliva, spit, mucous, vomitus, feces and blood 125 times in 48 hours. Only two of the 12 patient handwashing stations had running water and none had soap. No disinfection was observed before or after using medical instruments. Used medical supplies were often discarded in open containers under the beds. Handwashing with soap was observed in only 32 of 3,373 handwashing opportunities noted during 48 hours. Mosquitoes and feral cats were commonly observed in the wards. CONCLUSIONS: The physical structure and environment of our study hospitals are conducive to the spread of infection to people in the wards. Low-cost interventions on hand hygiene and cleaning procedures for rooms and medical equipment should be developed and evaluated for their practicality and effectiveness.",2014 Feb 19,"['Rimi, Nadia Ali', 'Sultana, Rebeca', 'Luby, Stephen P.', 'Islam, Mohammed Saiful', 'Uddin, Main', 'Hossain, Mohammad Jahangir', 'Zaman, Rashid Uz', 'Nahar, Nazmun', 'Gurley, Emily S.']",PLoS One,,,True
88395bf2fdca68c0eb033b14655275547bdcd714,PMC,Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1,http://dx.doi.org/10.1186/2045-3701-4-3,PMC3930072,24410900,CC BY,"BACKGROUND: Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. Spike (S) protein of SARS-CoV activates the unfolded protein response (UPR). It is not understood whether HCoV-HKU1 S protein has similar activity. In addition, the UPR-activating domain in SARS-CoV S protein remains to be identified. RESULTS: In this study we compared S proteins of SARS-CoV and HCoV-HKU1 for their ability to activate the UPR. Both S proteins were found in the endoplasmic reticulum. Transmembrane serine protease TMPRSS2 catalyzed the cleavage of SARS-CoV S protein, but not the counterpart in HCoV-HKU1. Both S proteins showed a similar pattern of UPR-activating activity. Through PERK kinase they activated the transcription of UPR effector genes such as Grp78, Grp94 and CHOP. N-linked glycosylation was not required for the activation of the UPR by S proteins. S1 subunit of SARS-CoV but not its counterpart in HCoV-HKU1 was capable of activating the UPR. A central region (amino acids 201–400) of SARS-CoV S1 was required for this activity. CONCLUSIONS: SARS-CoV and HCoV-HKU1 S proteins use distinct UPR-activating domains to exert the same modulatory effects on UPR signaling.",2014 Jan 13,"['Siu, Kam-Leung', 'Chan, Ching-Ping', 'Kok, Kin-Hang', 'Woo, Patrick C-Y', 'Jin, Dong-Yan']",Cell Biosci,,,True
8d2f1769c1de3d813cf910561ff0401fb9d75121,PMC,Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2,http://dx.doi.org/10.1371/journal.ppat.1003932,PMC3930559,24586153,CC BY,"Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.",2014 Feb 20,"['Lemey, Philippe', 'Rambaut, Andrew', 'Bedford, Trevor', 'Faria, Nuno', 'Bielejec, Filip', 'Baele, Guy', 'Russell, Colin A.', 'Smith, Derek J.', 'Pybus, Oliver G.', 'Brockmann, Dirk', 'Suchard, Marc A.']",PLoS Pathog,,,True
52032489740c2f7f90c18e0a2668e5c51a3862a3,PMC,Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2,http://dx.doi.org/10.1371/journal.ppat.1003932,PMC3930559,24586153,CC BY,"Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.",2014 Feb 20,"['Lemey, Philippe', 'Rambaut, Andrew', 'Bedford, Trevor', 'Faria, Nuno', 'Bielejec, Filip', 'Baele, Guy', 'Russell, Colin A.', 'Smith, Derek J.', 'Pybus, Oliver G.', 'Brockmann, Dirk', 'Suchard, Marc A.']",PLoS Pathog,,,False
864891b1bc35a03f305d3294e56b5c0870978f46,PMC,Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2,http://dx.doi.org/10.1371/journal.ppat.1003932,PMC3930559,24586153,CC BY,"Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.",2014 Feb 20,"['Lemey, Philippe', 'Rambaut, Andrew', 'Bedford, Trevor', 'Faria, Nuno', 'Bielejec, Filip', 'Baele, Guy', 'Russell, Colin A.', 'Smith, Derek J.', 'Pybus, Oliver G.', 'Brockmann, Dirk', 'Suchard, Marc A.']",PLoS Pathog,,,False
44c845b602b325eafa4b6a463b08967f456c59fb,PMC,Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2,http://dx.doi.org/10.1371/journal.ppat.1003932,PMC3930559,24586153,CC BY,"Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.",2014 Feb 20,"['Lemey, Philippe', 'Rambaut, Andrew', 'Bedford, Trevor', 'Faria, Nuno', 'Bielejec, Filip', 'Baele, Guy', 'Russell, Colin A.', 'Smith, Derek J.', 'Pybus, Oliver G.', 'Brockmann, Dirk', 'Suchard, Marc A.']",PLoS Pathog,,,False
5061a30dc9fa11fea2c38a44f8e5aaa5f31141fe,PMC,Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2,http://dx.doi.org/10.1371/journal.ppat.1003932,PMC3930559,24586153,CC BY,"Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.",2014 Feb 20,"['Lemey, Philippe', 'Rambaut, Andrew', 'Bedford, Trevor', 'Faria, Nuno', 'Bielejec, Filip', 'Baele, Guy', 'Russell, Colin A.', 'Smith, Derek J.', 'Pybus, Oliver G.', 'Brockmann, Dirk', 'Suchard, Marc A.']",PLoS Pathog,,,False
337e3a24fa905a564211c159d1fc5fc0fd93924d,PMC,Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2,http://dx.doi.org/10.1371/journal.ppat.1003932,PMC3930559,24586153,CC BY,"Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.",2014 Feb 20,"['Lemey, Philippe', 'Rambaut, Andrew', 'Bedford, Trevor', 'Faria, Nuno', 'Bielejec, Filip', 'Baele, Guy', 'Russell, Colin A.', 'Smith, Derek J.', 'Pybus, Oliver G.', 'Brockmann, Dirk', 'Suchard, Marc A.']",PLoS Pathog,,,False
ec5eb5ea6033d1a32e46cb874e3b87b9a700cd5a,PMC,Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2,http://dx.doi.org/10.1371/journal.ppat.1003932,PMC3930559,24586153,CC BY,"Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.",2014 Feb 20,"['Lemey, Philippe', 'Rambaut, Andrew', 'Bedford, Trevor', 'Faria, Nuno', 'Bielejec, Filip', 'Baele, Guy', 'Russell, Colin A.', 'Smith, Derek J.', 'Pybus, Oliver G.', 'Brockmann, Dirk', 'Suchard, Marc A.']",PLoS Pathog,,,True
03fd3a4ec79ffea2a049338b2818457e98496df6,PMC,Comparative In Vivo Analysis of Recombinant Type II Feline Coronaviruses with Truncated and Completed ORF3 Region,http://dx.doi.org/10.1371/journal.pone.0088758,PMC3930587,24586385,CC BY,"Our previous in vitro comparative study on a feline coronavirus (FCoV) pair, differing only in the intactness of their ORF3abc regions, showed that the truncated ORF3abc plays an important role in the efficient macrophage/monocyte tropism of type II feline infectious peritonitis virus (FIPV). In the present study, we describe a challenge experiment with the same recombinant FCoVs in order to gain data on the in vivo characteristics on these viruses. While parent virus FIPV DF-2 developed feline infectious peritonitis in all the infected cats, its recombinant virus PBFIPV-DF-2, differing only in seven nucleotides, proved to be surprisingly low virulent, although caused an acute febrile episode similarly to the original FIPV DF-2. PBFIPV-DF-2 infection induced significantly lower virus neutralization titers than its parent virus, and lacked the second phase of viremia and development of fatal course of the disease. The recombinant PBFIPV-DF-2-R3i with completed ORF3abc gained biological properties that differentiate between the feline enteric coronavirus (FECV) and FIPV biotypes such as intensive replication in the gut, absence of viremia and weak or no serological response. Using reverse genetic approaches our study is the first experimental proof that ORF3abc is indeed responsible for the restriction of FECV replication to the intestine in vivo.",2014 Feb 20,"['Bálint, Ádám', 'Farsang, Attila', 'Zádori, Zoltán', 'Belák, Sándor']",PLoS One,,,True
bb6a9f522a87a780723faca7cde002ece6dbfb48,PMC,A novel reporter system for neutralizing and enhancing antibody assay against dengue virus,http://dx.doi.org/10.1186/1471-2180-14-44,PMC3930823,24548533,CC BY,"BACKGROUND: Dengue virus (DENV) still poses a global public health threat, and no vaccine or antiviral therapy is currently available. Antibody plays distinct roles in controlling DENV infections. Neutralizing antibody is protective against DENV infection, whereas sub-neutralizing concentration of antibody can increase DENV infection, termed antibody-dependent enhancement (ADE). Plaque-based assay represents the most widely accepted method measuring neutralizing or enhancing antibodies. RESULTS: In this study, a novel reporter virus-based system was developed for measuring neutralization and ADE activity. A stable Renilla luciferase reporter DENV (Luc-DENV) that can produce robust luciferase signals in BHK-21 and K562 cells were used to establish the assay and validated against traditional plaque-based assay. Luciferase value analysis using various known DENV-specific monoclonal antibodies showed good repeatability and a well linear correlation with conventional plaque-based assays. The newly developed assay was finally validated with clinical samples from infected animals and individuals. CONCLUSIONS: This reporter virus-based assay for neutralizing and enhancing antibody evaluation is rapid, lower cost, and high throughput, and will be helpful for laboratory detection and epidemiological investigation for DENV antibodies.",2014 Feb 18,"['Song, Ke-Yu', 'Zhao, Hui', 'Jiang, Zhen-You', 'Li, Xiao-Feng', 'Deng, Yong-Qiang', 'Jiang, Tao', 'Zhu, Shun-Ya', 'Shi, Pei-Yong', 'Zhang, Bo', 'Zhang, Fu-Chun', 'Qin, E-De', 'Qin, Cheng-Feng']",BMC Microbiol,,,True
1c857d4493720168ac6eba2bbeb2fbfa31433d91,PMC,Functional Fcgamma Receptor Polymorphisms Are Associated with Human Allergy,http://dx.doi.org/10.1371/journal.pone.0089196,PMC3931680,24586589,CC BY,"OBJECTIVE: IgG Fc receptors (FcγRs) play important roles in immune responses. It is not clear whether FcγR receptors play a role in human asthma and allergy. The aim of current study was to investigate whether functional single nucleotide polymorphisms (SNPs) of FcγR genes (FCGR) are associated with human asthma and allergy. METHODS: Functional SNPs of FCGR2A (FcγRIIA-131His>Arg, rs1801274), FCGR2B (FcγRIIB-187Ile>Thr, rs1050501), FCGR2C (FcγRIIC-13Gln>Stop, rs10917661), FCGR3A (FcγRIIIA-158Val>Phe, rs396991), and FCGR3B variants (FcγRIIIB NA1 and NA2) were genotyped in an asthma family cohort including 370 atopy positive, 239 atopy negative, and 169 asthma positive subjects. The genotype and phenotype data (asthma, bronchial hyper-responsiveness, and atopy) of subjects were analyzed using family-based association tests (FBAT) and logistic regression adjusted for age and sex. RESULT: The FcγRIIA-131His>Arg SNP is significantly associated with atopy in a family-based association test (P = 0.00287) and in a logistic regression analysis (P = 0.0269, OR 0.732, 95% CI: 0.555–0.965). The FcγRIIA-131His (or rs1801274-A) allele capable of binding human IgG2 has a protective role against atopy. In addition, the rare FcγRIIB-187Thr (or rs1050501-C) allele defective for the receptor-mediated inhibitory signals is a risk factor for atopy (P = 0.0031, OR 1.758, 95% CI: 1.209–2.556) and IgE production (P<0.001). However, variants of activating FcγRIIIA (rs396991), and FcγRIIIB (NA1 and NA2), and FcγRIIC (rs10917661) are not associated with asthma, BHR, and atopy (P>0.05). CONCLUSIONS: FcγRIIA and FcγRIIB functional polymorphisms may have a role in the pathogenesis of allergy.",2014 Feb 21,"['Wu, Jianming', 'Lin, Rui', 'Huang, Jinhai', 'Guan, Weihua', 'Oetting, William S.', 'Sriramarao, P.', 'Blumenthal, Malcolm N.']",PLoS One,,,True
e74b146de222afb1af191265d849fc86048712bc,PMC,Nano-ZnO Catalyzed Multicomponent One-Pot Synthesis of Novel Spiro(indoline-pyranodioxine) Derivatives,http://dx.doi.org/10.1155/2014/427195,PMC3933407,24683341,CC BY,"A simple catalytic protocol for the synthesis of novel spiro[indoline-pyranodioxine] derivatives has been developed using ZnO nanoparticle as an efficient, green, and reusable catalyst. The derivatives are obtained in moderate to excellent yield by one-pot three-component reaction of an isatin, malononitrile/ethylcyanoacetate, and 2,2-dimethyl-1,3-dioxane-4,6-dione in absolute ethanol under conventional heating and microwave irradiation. The catalyst was recovered by filtration from the reaction mixture and reused during five consecutive runs without any apparent loss of activity for the same reaction. The mild reaction conditions and recyclability of the catalyst make it environmentally benign synthetic procedure.",2014 Feb 5,"['Sachdeva, Harshita', 'Saroj, Rekha', 'Dwivedi, Diksha']",ScientificWorldJournal,,,True
7f62acc34c68b857a7bf8a4868fdd75d312720e9,PMC,"Population-Based Incidence of Severe Acute Respiratory Virus Infections among Children Aged <5 Years in Rural Bangladesh, June–October 2010",http://dx.doi.org/10.1371/journal.pone.0089978,PMC3934972,24587163,CC0,"BACKGROUND: Better understanding the etiology-specific incidence of severe acute respiratory infections (SARIs) in resource-poor, rural settings will help further develop and prioritize prevention strategies. To address this gap in knowledge, we conducted a longitudinal study to estimate the incidence of SARIs among children in rural Bangladesh. METHODS: During June through October 2010, we followed children aged <5 years in 67 villages to identify those with cough, difficulty breathing, age-specific tachypnea and/or danger signs in the community or admitted to the local hospital. A study physician collected clinical information and obtained nasopharyngeal swabs from all SARI cases and blood for bacterial culture from those hospitalized. We tested swabs for respiratory syncytial virus (RSV), influenza viruses, human metapneumoviruses, adenoviruses and human parainfluenza viruses 1–3 (HPIV) by real-time reverse transcription polymerase chain reaction. We calculated virus-specific SARI incidence by dividing the number of new illnesses by the person-time each child contributed to the study. RESULTS: We followed 12,850 children for 279,029 person-weeks (pw) and identified 141 SARI cases; 76 (54%) at their homes and 65 (46%) at the hospital. RSV was associated with 7.9 SARI hospitalizations per 100,000 pw, HPIV3 2.2 hospitalizations/100,000 pw, and influenza 1.1 hospitalizations/100,000 pw. Among non-hospitalized SARI cases, RSV was associated with 10.8 illnesses/100,000 pw, HPIV3 1.8/100,000 pw, influenza 1.4/100,000 pw, and adenoviruses 0.4/100,000 pw. CONCLUSION: Respiratory viruses, particularly RSV, were commonly associated with SARI among children. It may be useful to explore the value of investing in prevention strategies, such as handwashing and respiratory hygiene, to reduce respiratory infections among young children in such settings.",2014 Feb 25,"['Nasreen, Sharifa', 'Luby, Stephen P.', 'Brooks, W. Abdullah', 'Homaira, Nusrat', 'Mamun, Abdullah Al', 'Bhuiyan, Mejbah Uddin', 'Rahman, Mustafizur', 'Ahmed, Dilruba', 'Abedin, Jaynal', 'Rahman, Mahmudur', 'Alamgir, A. S. M.', 'Fry, Alicia M.', 'Streatfield, Peter Kim', 'Rahman, Anisur', 'Bresee, Joseph', 'Widdowson, Marc-Alain', 'Azziz-Baumgartner, Eduardo']",PLoS One,,,True
540ccda8bb32d2b9192782b878cc2759da109212,PMC,Evolution and Structural Organization of the C Proteins of Paramyxovirinae,http://dx.doi.org/10.1371/journal.pone.0090003,PMC3934983,24587180,CC0,"The phosphoprotein (P) gene of most Paramyxovirinae encodes several proteins in overlapping frames: P and V, which share a common N-terminus (PNT), and C, which overlaps PNT. Overlapping genes are of particular interest because they encode proteins originated de novo, some of which have unknown structural folds, challenging the notion that nature utilizes only a limited, well-mapped area of fold space. The C proteins cluster in three groups, comprising measles, Nipah, and Sendai virus. We predicted that all C proteins have a similar organization: a variable, disordered N-terminus and a conserved, α-helical C-terminus. We confirmed this predicted organization by biophysically characterizing recombinant C proteins from Tupaia paramyxovirus (measles group) and human parainfluenza virus 1 (Sendai group). We also found that the C of the measles and Nipah groups have statistically significant sequence similarity, indicating a common origin. Although the C of the Sendai group lack sequence similarity with them, we speculate that they also have a common origin, given their similar genomic location and structural organization. Since C is dispensable for viral replication, unlike PNT, we hypothesize that C may have originated de novo by overprinting PNT in the ancestor of Paramyxovirinae. Intriguingly, in measles virus and Nipah virus, PNT encodes STAT1-binding sites that overlap different regions of the C-terminus of C, indicating they have probably originated independently. This arrangement, in which the same genetic region encodes simultaneously a crucial functional motif (a STAT1-binding site) and a highly constrained region (the C-terminus of C), seems paradoxical, since it should severely reduce the ability of the virus to adapt. The fact that it originated twice suggests that it must be balanced by an evolutionary advantage, perhaps from reducing the size of the genetic region vulnerable to mutations.",2014 Feb 25,"['Lo, Michael K.', 'Søgaard, Teit Max', 'Karlin, David G.']",PLoS One,,,True
12590435a221d10824ab106e66d0f9fec397db40,PMC,The output of the tRNA modification pathways controlled by the Escherichia coli MnmEG and MnmC enzymes depends on the growth conditions and the tRNA species,http://dx.doi.org/10.1093/nar/gkt1228,PMC3936742,24293650,CC BY,"In Escherichia coli, the MnmEG complex modifies transfer RNAs (tRNAs) decoding NNA/NNG codons. MnmEG catalyzes two different modification reactions, which add an aminomethyl (nm) or carboxymethylaminomethyl (cmnm) group to position 5 of the anticodon wobble uridine using ammonium or glycine, respectively. In [Image: see text] and [Image: see text], however, cmnm(5) appears as the final modification, whereas in the remaining tRNAs, the MnmEG products are converted into 5-methylaminomethyl (mnm(5)) through the two-domain, bi-functional enzyme MnmC. MnmC(o) transforms cmnm(5) into nm(5), whereas MnmC(m) converts nm(5) into mnm(5), thus producing an atypical network of modification pathways. We investigate the activities and tRNA specificity of MnmEG and the MnmC domains, the ability of tRNAs to follow the ammonium or glycine pathway and the effect of mnmC mutations on growth. We demonstrate that the two MnmC domains function independently of each other and that [Image: see text] and [Image: see text] are substrates for MnmC(m), but not MnmC(o). Synthesis of mnm(5)s(2)U by MnmEG-MnmC in vivo avoids build-up of intermediates in [Image: see text]. We also show that MnmEG can modify all the tRNAs via the ammonium pathway. Strikingly, the net output of the MnmEG pathways in vivo depends on growth conditions and tRNA species. Loss of any MnmC activity has a biological cost under specific conditions.",2014 Feb 26,"['Moukadiri, Ismaïl', 'Garzón, M.-José', 'Björk, Glenn R.', 'Armengod, M.-Eugenia']",Nucleic Acids Res,,,True
1d46e668687f5f0244a551b292f5567358f3bf3d,PMC,The output of the tRNA modification pathways controlled by the Escherichia coli MnmEG and MnmC enzymes depends on the growth conditions and the tRNA species,http://dx.doi.org/10.1093/nar/gkt1228,PMC3936742,24293650,CC BY,"In Escherichia coli, the MnmEG complex modifies transfer RNAs (tRNAs) decoding NNA/NNG codons. MnmEG catalyzes two different modification reactions, which add an aminomethyl (nm) or carboxymethylaminomethyl (cmnm) group to position 5 of the anticodon wobble uridine using ammonium or glycine, respectively. In [Image: see text] and [Image: see text], however, cmnm(5) appears as the final modification, whereas in the remaining tRNAs, the MnmEG products are converted into 5-methylaminomethyl (mnm(5)) through the two-domain, bi-functional enzyme MnmC. MnmC(o) transforms cmnm(5) into nm(5), whereas MnmC(m) converts nm(5) into mnm(5), thus producing an atypical network of modification pathways. We investigate the activities and tRNA specificity of MnmEG and the MnmC domains, the ability of tRNAs to follow the ammonium or glycine pathway and the effect of mnmC mutations on growth. We demonstrate that the two MnmC domains function independently of each other and that [Image: see text] and [Image: see text] are substrates for MnmC(m), but not MnmC(o). Synthesis of mnm(5)s(2)U by MnmEG-MnmC in vivo avoids build-up of intermediates in [Image: see text]. We also show that MnmEG can modify all the tRNAs via the ammonium pathway. Strikingly, the net output of the MnmEG pathways in vivo depends on growth conditions and tRNA species. Loss of any MnmC activity has a biological cost under specific conditions.",2014 Feb 26,"['Moukadiri, Ismaïl', 'Garzón, M.-José', 'Björk, Glenn R.', 'Armengod, M.-Eugenia']",Nucleic Acids Res,,,False
e2b6aa71fbb89c9a10e9b00f36313ba5be05b025,PMC,A cypovirus VP5 displays the RNA chaperone-like activity that destabilizes RNA helices and accelerates strand annealing,http://dx.doi.org/10.1093/nar/gkt1256,PMC3936753,24319147,CC BY,"For double-stranded RNA (dsRNA) viruses in the family Reoviridae, their inner capsids function as the machinery for viral RNA (vRNA) replication. Unlike other multishelled reoviruses, cypovirus has a single-layered capsid, thereby representing a simplified model for studying vRNA replication of reoviruses. VP5 is one of the three major cypovirus capsid proteins and functions as a clamp protein to stabilize cypovirus capsid. Here, we expressed VP5 from type 5 Helicoverpa armigera cypovirus (HaCPV-5) in a eukaryotic system and determined that this VP5 possesses RNA chaperone-like activity, which destabilizes RNA helices and accelerates strand annealing independent of ATP. Our further characterization of VP5 revealed that its helix-destabilizing activity is RNA specific, lacks directionality and could be inhibited by divalent ions, such as Mg(2+), Mn(2+), Ca(2+) or Zn(2+), to varying degrees. Furthermore, we found that HaCPV-5 VP5 facilitates the replication initiation of an alternative polymerase (i.e. reverse transcriptase) through a panhandle-structured RNA template, which mimics the 5′-3′ cyclization of cypoviral positive-stranded RNA. Given that the replication of negative-stranded vRNA on the positive-stranded vRNA template necessitates the dissociation of the 5′-3′ panhandle, the RNA chaperone activity of VP5 may play a direct role in the initiation of reoviral dsRNA synthesis.",2014 Feb 5,"['Yang, Jie', 'Cheng, Zhenyun', 'Zhang, Songliu', 'Xiong, Wei', 'Xia, Hongjie', 'Qiu, Yang', 'Wang, Zhaowei', 'Wu, Feige', 'Qin, Cheng-Feng', 'Yin, Lei', 'Hu, Yuanyang', 'Zhou, Xi']",Nucleic Acids Res,,,True
aeb9f61c19077eaf906fd7baf5bcf4e010dc6fa6,PMC,A cypovirus VP5 displays the RNA chaperone-like activity that destabilizes RNA helices and accelerates strand annealing,http://dx.doi.org/10.1093/nar/gkt1256,PMC3936753,24319147,CC BY,"For double-stranded RNA (dsRNA) viruses in the family Reoviridae, their inner capsids function as the machinery for viral RNA (vRNA) replication. Unlike other multishelled reoviruses, cypovirus has a single-layered capsid, thereby representing a simplified model for studying vRNA replication of reoviruses. VP5 is one of the three major cypovirus capsid proteins and functions as a clamp protein to stabilize cypovirus capsid. Here, we expressed VP5 from type 5 Helicoverpa armigera cypovirus (HaCPV-5) in a eukaryotic system and determined that this VP5 possesses RNA chaperone-like activity, which destabilizes RNA helices and accelerates strand annealing independent of ATP. Our further characterization of VP5 revealed that its helix-destabilizing activity is RNA specific, lacks directionality and could be inhibited by divalent ions, such as Mg(2+), Mn(2+), Ca(2+) or Zn(2+), to varying degrees. Furthermore, we found that HaCPV-5 VP5 facilitates the replication initiation of an alternative polymerase (i.e. reverse transcriptase) through a panhandle-structured RNA template, which mimics the 5′-3′ cyclization of cypoviral positive-stranded RNA. Given that the replication of negative-stranded vRNA on the positive-stranded vRNA template necessitates the dissociation of the 5′-3′ panhandle, the RNA chaperone activity of VP5 may play a direct role in the initiation of reoviral dsRNA synthesis.",2014 Feb 5,"['Yang, Jie', 'Cheng, Zhenyun', 'Zhang, Songliu', 'Xiong, Wei', 'Xia, Hongjie', 'Qiu, Yang', 'Wang, Zhaowei', 'Wu, Feige', 'Qin, Cheng-Feng', 'Yin, Lei', 'Hu, Yuanyang', 'Zhou, Xi']",Nucleic Acids Res,,,False
2895e9bc46487b11d2e514ed42fca059df5ec7a6,PMC,Public health human resources: a comparative analysis of policy documents in two Canadian provinces,http://dx.doi.org/10.1186/1478-4491-12-13,PMC3936858,24564931,CC BY,"BACKGROUND: Amidst concerns regarding the capacity of the public health system to respond rapidly and appropriately to threats such as pandemics and terrorism, along with changing population health needs, governments have focused on strengthening public health systems. A key factor in a robust public health system is its workforce. As part of a nationally funded study of public health renewal in Canada, a policy analysis was conducted to compare public health human resources-relevant documents in two Canadian provinces, British Columbia (BC) and Ontario (ON), as they each implement public health renewal activities. METHODS: A content analysis of policy and planning documents from government and public health-related organizations was conducted by a research team comprised of academics and government decision-makers. Documents published between 2003 and 2011 were accessed (BC = 27; ON = 20); documents were either publicly available or internal to government and excerpted with permission. Documentary texts were deductively coded using a coding template developed by the researchers based on key health human resources concepts derived from two national policy documents. RESULTS: Documents in both provinces highlighted the importance of public health human resources planning and policies; this was particularly evident in early post-SARS documents. Key thematic areas of public health human resources identified were: education, training, and competencies; capacity; supply; intersectoral collaboration; leadership; public health planning context; and priority populations. Policy documents in both provinces discussed the importance of an educated, competent public health workforce with the appropriate skills and competencies for the effective and efficient delivery of public health services. CONCLUSION: This policy analysis identified progressive work on public health human resources policy and planning with early documents providing an inventory of issues to be addressed and later documents providing evidence of beginning policy development and implementation. While many similarities exist between the provinces, the context distinctive to each province has influenced and shaped how they have focused their public health human resources policies.",2014 Feb 24,"['Regan, Sandra', 'MacDonald, Marjorie', 'Allan, Diane E', 'Martin, Cheryl', 'Peroff-Johnston, Nancy']",Hum Resour Health,,,True
0245907283f094332e4062539e495f880c6994f6,PMC,Public health human resources: a comparative analysis of policy documents in two Canadian provinces,http://dx.doi.org/10.1186/1478-4491-12-13,PMC3936858,24564931,CC BY,"BACKGROUND: Amidst concerns regarding the capacity of the public health system to respond rapidly and appropriately to threats such as pandemics and terrorism, along with changing population health needs, governments have focused on strengthening public health systems. A key factor in a robust public health system is its workforce. As part of a nationally funded study of public health renewal in Canada, a policy analysis was conducted to compare public health human resources-relevant documents in two Canadian provinces, British Columbia (BC) and Ontario (ON), as they each implement public health renewal activities. METHODS: A content analysis of policy and planning documents from government and public health-related organizations was conducted by a research team comprised of academics and government decision-makers. Documents published between 2003 and 2011 were accessed (BC = 27; ON = 20); documents were either publicly available or internal to government and excerpted with permission. Documentary texts were deductively coded using a coding template developed by the researchers based on key health human resources concepts derived from two national policy documents. RESULTS: Documents in both provinces highlighted the importance of public health human resources planning and policies; this was particularly evident in early post-SARS documents. Key thematic areas of public health human resources identified were: education, training, and competencies; capacity; supply; intersectoral collaboration; leadership; public health planning context; and priority populations. Policy documents in both provinces discussed the importance of an educated, competent public health workforce with the appropriate skills and competencies for the effective and efficient delivery of public health services. CONCLUSION: This policy analysis identified progressive work on public health human resources policy and planning with early documents providing an inventory of issues to be addressed and later documents providing evidence of beginning policy development and implementation. While many similarities exist between the provinces, the context distinctive to each province has influenced and shaped how they have focused their public health human resources policies.",2014 Feb 24,"['Regan, Sandra', 'MacDonald, Marjorie', 'Allan, Diane E', 'Martin, Cheryl', 'Peroff-Johnston, Nancy']",Hum Resour Health,,,False
2bfe733ac66d7514f07e3c7ceb2a58dea87f922b,PMC,Public health human resources: a comparative analysis of policy documents in two Canadian provinces,http://dx.doi.org/10.1186/1478-4491-12-13,PMC3936858,24564931,CC BY,"BACKGROUND: Amidst concerns regarding the capacity of the public health system to respond rapidly and appropriately to threats such as pandemics and terrorism, along with changing population health needs, governments have focused on strengthening public health systems. A key factor in a robust public health system is its workforce. As part of a nationally funded study of public health renewal in Canada, a policy analysis was conducted to compare public health human resources-relevant documents in two Canadian provinces, British Columbia (BC) and Ontario (ON), as they each implement public health renewal activities. METHODS: A content analysis of policy and planning documents from government and public health-related organizations was conducted by a research team comprised of academics and government decision-makers. Documents published between 2003 and 2011 were accessed (BC = 27; ON = 20); documents were either publicly available or internal to government and excerpted with permission. Documentary texts were deductively coded using a coding template developed by the researchers based on key health human resources concepts derived from two national policy documents. RESULTS: Documents in both provinces highlighted the importance of public health human resources planning and policies; this was particularly evident in early post-SARS documents. Key thematic areas of public health human resources identified were: education, training, and competencies; capacity; supply; intersectoral collaboration; leadership; public health planning context; and priority populations. Policy documents in both provinces discussed the importance of an educated, competent public health workforce with the appropriate skills and competencies for the effective and efficient delivery of public health services. CONCLUSION: This policy analysis identified progressive work on public health human resources policy and planning with early documents providing an inventory of issues to be addressed and later documents providing evidence of beginning policy development and implementation. While many similarities exist between the provinces, the context distinctive to each province has influenced and shaped how they have focused their public health human resources policies.",2014 Feb 24,"['Regan, Sandra', 'MacDonald, Marjorie', 'Allan, Diane E', 'Martin, Cheryl', 'Peroff-Johnston, Nancy']",Hum Resour Health,,,False
69e95489dff0da006349ceb3a46a1f215cb1b910,PMC,"Myosins 1 and 6, myosin light chain kinase, actin and microtubules cooperate during antibody-mediated internalisation and trafficking of membrane-expressed viral antigens in feline infectious peritonitis virus infected monocytes",http://dx.doi.org/10.1186/1297-9716-45-17,PMC3937040,24517254,CC BY,"Monocytes infected with feline infectious peritonitis virus, a coronavirus, express viral proteins in their plasma membranes. Upon binding of antibodies, these proteins are quickly internalised through a new clathrin- and caveolae-independent internalisation pathway. By doing so, the infected monocytes can escape antibody-dependent cell lysis. In the present study, we investigated which kinases and cytoskeletal proteins are of importance during internalisation and subsequent intracellular transport. The experiments showed that myosin light chain kinase (MLCK) and myosin 1 are crucial for the initiation of the internalisation. With co-localisation stainings, it was found that MLCK and myosin 1 co-localise with antigens even before internalisation started. Myosin 6 co-localised with the internalising complexes during passage through the cortical actin, were it might play a role in moving or disintegrating actin filaments, to overcome the actin barrier. One minute after internalisation started, vesicles had passed the cortical actin, co-localised with microtubules and association with myosin 6 was lost. The vesicles were further transported over the microtubules and accumulated at the microtubule organising centre after 10 to 30 min. Intracellular trafficking over microtubules was mediated by MLCK, myosin 1 and a small actin tail. Since inhibiting MLCK with ML-7 was so efficient in blocking the internalisation pathway, this target can be used for the development of a new treatment for FIPV.",2014 Feb 12,"['Dewerchin, Hannah L', 'Desmarets, Lowiese M', 'Noppe, Ytse', 'Nauwynck, Hans J']",Vet Res,,,True
4e741d57fb2db417d3a82fae701233ed7d4c5b55,PMC,Chinese immigrant parents’ vaccination decision making for children: a qualitative analysis,http://dx.doi.org/10.1186/1471-2458-14-133,PMC3937074,24507384,CC BY,"BACKGROUND: While immunization coverage rates for childhood routine vaccines in Hong Kong are almost 100%, the uptake rates of optional vaccines remain suboptimal. Understanding parental decision-making for children’s vaccination is important, particularly among minority groups who are most vulnerable and underserved. This study explored how a subsample of new immigrant mothers from mainland China, a rapidly-growing subpopulation in Hong Kong, made decisions on various childhood and adolescent vaccines for their offspring, and identified key influences affecting their decision making. METHODS: Semi-structured in-depth interviews were conducted with 23 Chinese new immigrant mothers recruited by purposive sampling. All interviews were audio-taped, transcribed and analyzed using a Grounded Theory approach. RESULTS: Participants’ conversation revealed five underlying themes which influenced parents’ vaccination decision-making: (1) Institutional factors, (2) Insufficient vaccination knowledge and advice, (3) Affective impacts on motivation, (4) Vaccination barriers, and (5) Social influences. The role of social norms appeared overwhelmingly salient influencing parents’ vaccination decision making. Institutional factors shaped parent’s perceptions of vaccination necessity. Fear of vaccine-targeted diseases was a key motivating factor for parents adopting vaccination. Insufficient knowledge about vaccines and targeted diseases, lack of advice from health professionals and, if provided, suspicions regarding the motivations for such advice were common issues. Vaccination cost was a major barrier for many new immigrant parents. CONCLUSIONS: Social norms play a key role influencing parental vaccination decision-making. Insight gained from this study will help inform healthcare providers in vaccination communication and policymakers in future vaccination programme.",2014 Feb 7,"['Wang, Linda DL', 'Lam, Wendy WT', 'Wu, Joseph T', 'Liao, Qiuyan', 'Fielding, Richard']",BMC Public Health,,,True
fd28c322b33337c09ccb3d0785d8c2494efa0946,PMC,Rapid PCR/ESI-MS-based molecular genotyping of Staphylococcus aureus from nasal swabs of emergency department patients,http://dx.doi.org/10.1186/1471-2334-14-16,PMC3937163,24405766,CC BY,"BACKGROUND: A limitation of both culture-based and molecular methods of screening for staphylococcal infection is that current tests determine only the presence or absence of colonization with no information on the colonizing strain type. A technique that couples polymerase chain reaction to mass spectrometry (PCR/ESI-MS) has recently been developed and an assay validated to identify and genotype S. aureus and coagulase-negative staphylococci (CoNS). METHODS: This study was conducted to determine the rates, risk factors, and molecular genotypes of colonizing Staphylococcus aureus in adult patients presenting to an inner-city academic emergency department. Participants completed a structured questionnaire to assess hospital and community risks for infection with methicillin-resistant S. aureus (MRSA). Nasal swabs were analyzed by PCR/ESI-MS to identify and genotype S. aureus and CoNS. RESULTS: Of 200 patients evaluated, 59 were colonized with S. aureus; 27 of these were methicillin-resistant strains. Twenty-four of the 59 S. aureus carriers were co-colonized with a CoNS and 140 of the 200 patients were colonized exclusively with CoNS. The molecular genotypes of the 59 S. aureus strains were diverse; 21 unique molecular genotypes belonging to seven major clonal complexes were identified. Eighty-five of 200 patients carried strains with high-level mupirocin resistance. Of these eighty-five participants, 4 were colonized exclusively with S. aureus, 16 were co-colonized with S. aureus and CoNS, and 65 were colonized exclusively with CoNS. CONCLUSION: The prevalence of S. aureus and methicillin-resistant S. aureus colonization in a random sample of patients seeking care in Emergency Department was 29.5% and 13.5%, respectively. A substantial fraction of the S. aureus-colonized patients were co-colonized with CoNS and high-level mupirocin-resistant CoNS. Determining the molecular genotype of S. aureus during intake screening may prove valuable in the future if certain molecular genotypes become associated with increased infection risk.",2014 Jan 9,"['Kecojevic, Aleksandar', 'Ranken, Ray', 'Ecker, David J', 'Massire, Christian', 'Sampath, Rangarajan', 'Blyn, Lawrence B', 'Hsieh, Yu-Hsiang', 'Rothman, Richard E', 'Gaydos, Charlotte A']",BMC Infect Dis,,,True
0b22db40e9e78fb29f6ae2938ed8ee2d00cd46b2,PMC,Disassembly of the cystovirus ϕ6 envelope by montmorillonite clay,http://dx.doi.org/10.1002/mbo3.148,PMC3937728,24357622,CC BY,"Prior studies of clay–virus interactions have focused on the stability and infectivity of nonenveloped viruses, yielding contradictory results. We hypothesize that the surface charge distribution of the clay and virus envelope dictates how the components react and affect aggregation, viral stability, and infectivity. The bacteriophage Cystoviridae species φ6 used in this study is a good model for enveloped pathogens. The interaction between φ6 and montmorillonite (MMT) clay (the primary component of bentonite) is explored by transmission electron microscopy. The analyses show that MMT–φ6 mixtures undergo heteroaggregation, forming structures in which virtually all the virions are either sequestered between MMT platelet layers or attached to platelet edges. The virions swell and undergo disassembly resulting in partial or total envelope loss. Edge-attached viral envelopes distort to increase contact area with the positively charged platelet edges indicating that the virion surface is negatively charged. The nucleocapsid (NCs) remaining after envelope removal also exhibit distortion, in contrast to detergent-produced NCs which exhibit no distortion. This visually discernible disassembly is a mechanism for loss of infectivity previously unreported by studies of nonenveloped viruses. The MMT-mediated sequestration and disassembly result in reduced infectivity, suggesting that clays may reduce infectivity of enveloped pathogenic viruses in soils and sediments.",2014 Feb 19,"['Block, Karin A', 'Trusiak, Adrianna', 'Katz, Al', 'Gottlieb, Paul', 'Alimova, Alexandra', 'Wei, Hui', 'Morales, Jorge', 'Rice, William J', 'Steiner, Jeffrey C']",Microbiologyopen,,,True
22977df2b5a35dfe536faa4bd77a21ab316dc9f8,PMC,Long-Term Single-Dose Efficacy of a Vesicular Stomatitis Virus-Based Andes Virus Vaccine in Syrian Hamsters,http://dx.doi.org/10.3390/v6020516,PMC3939469,24492621,CC BY,"Andes virus (ANDV) is highly pathogenic in humans and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in South America. Case-fatality rates are as high as 50% and there are no approved vaccines or specific therapies for infection. Our laboratory has recently developed a replication-competent recombinant vesicular stomatitis virus (VSV)-based vaccine that expressed the glycoproteins of Andes virus in place of the native VSV glycoprotein (G). This vaccine is highly efficacious in the Syrian hamster model of HCPS when given 28 days before challenge with ANDV, or when given around the time of challenge (peri-exposure), and even protects when administered post-exposure. Herein, we sought to test the durability of the immune response to a single dose of this vaccine in Syrian hamsters. This vaccine was efficacious in hamsters challenged intranasally with ANDV 6 months after vaccination (p = 0.025), but animals were not significantly protected following 1 year of vaccination (p = 0.090). The decrease in protection correlated with a reduction of measurable neutralizing antibody responses, and suggests that a more robust vaccination schedule might be required to provide long-term immunity.",2014 Jan 31,"['Prescott, Joseph', 'DeBuysscher, Blair L.', 'Brown, Kyle S.', 'Feldmann, Heinz']",Viruses,,,True
b76a42e03efa0717d687c09551b0fb2a3cf116b9,PMC,Molecular Analysis of Human Metapneumovirus Detected in Patients with Lower Respiratory Tract Infection in Upper Egypt,http://dx.doi.org/10.1155/2014/290793,PMC3941176,24669221,CC BY,"Introduction. Since 2001, when Human metapneumovirus (HMPV) was isolated in the Netherlands, the virus has been detected in several continents. Although reports have confirmed the prevalence of HMPV worldwide, data from Egypt remain limited. HMPV plays an important role in respiratory tract infections in individuals of all ages particularly in children. This study was aimed at estimating the prevalence of HMPV in patients with community-acquired lower respiratory infection in Upper Egypt and characterizing the circulating Egyptian HMPV strains for the first time. Materials and Methods. From 2005 to 2008, respiratory samples from 520 patients were analyzed for the presence of HMPV by real-time RT-PCR. Molecular and phylogenetic analyses were performed on partial fusion gene sequences of HMPV-positive patients. Results. HMPV-positive patients were detected in 2007-2008. The overall infection rate was 4%, while 57% of the patients were children. Sequence analysis demonstrated circulation of subgroup B viruses with predominance of lineage B2. Nucleotide sequence identity within lineage B1 was 98.8%–99.7% and higher than that in lineage B2 (94.3%–100%). Three new amino acid substitutions (T223N, R229K, and D280N) of lineage B2 were observed. Conclusion. HMPV is a major viral pathogen in the Egyptian population especially in children. During 2007-2008, predominantly HMPV B2 circulated in Upper Egypt.",2014 Jan 30,"['Embarek Mohamed, Mona S.', 'Reiche, Janine', 'Jacobsen, Sonja', 'Thabit, Amany G.', 'Badary, Mohamed S.', 'Brune, Wolfram', 'Schweiger, Brunhilde', 'Osmann, Ahmed H.']",Int J Microbiol,,,True
4d2c66f3c30a2fd8f14f75c3f5405e2ba61b9345,PMC,Giardiosis and other enteropathogenic infections: a study on diarrhoeic calves in Southern Germany,http://dx.doi.org/10.1186/1756-0500-7-112,PMC3941484,24568139,CC BY,"BACKGROUND: Diarrhoea induces massive problems in the rearing of calves. The aim of the study was to obtain current data about the frequency of Giardia spp., Cryptosporidium spp. and Eimeria spp. in diarrhoeic calves in Southern Germany with the particular focus on giardiosis. RESULTS: 1564 samples were analysed for the three pathogens using microscopical methods. Giardia spp. was detectable in 112/1564 samples (7.2%). The mean age was 46.5 days and the odds of being infected with Giardia spp. increased slowly up to 8 times from about 12 days to 30 days of age. There appeared to be no seasonal influence on the frequency of Giardia spp. A mono-infection with Giardia spp. was diagnosed in 46 calves (2.9%) whereas 15 calves (1.0%) had a mixed-infection with Cryptosporidium spp. and 51 calves (3.3%) with Eimeria spp. Cryptosporidium spp. and Eimeria spp. could be detected in 646/1564 samples (41.3%) and 208/1564 samples (13.3%), respectively, with a mean age of 11.3 and 55.0 days, respectively. The odds of being infected with Cryptosporidium spp. increased up to 4.5 times until an age of 10 days. After that the odds decreased continuously and was approaching zero at about 30 days. The odds of being infected with Eimeria spp. increased continuously up to 30 times from about 20 days to 60 days of age. There appeared to be no significant seasonal influence on the frequency of Cryptosporidium spp.; but there was one for Eimeria spp.: the odds of being infected with Eimeria spp. in March and April decreased by about half and increased up to 2.3 times between July and September. Additionally, as requested by the veterinarians, 1282 of those samples were analysed for E. coli, Rota-, Coronavirus and Cryptosporidium spp. using an ELISA. Obtained frequencies for these pathogens were 0.9%, 37.8%, 3.4% and 45.3% with a mean age of 24.8 days, 12.1 days, 9.0 days and 12.1 days, respectively. CONCLUSIONS: The results indicate that in Southern Germany in addition to Eimeria spp., Giardia spp. seems to play a contributing role in diarrhoea in older calves, whereas Cryptosporidium spp. and Rotavirus are mostly relevant in young calves.",2014 Feb 26,"['Gillhuber, Julia', 'Rügamer, David', 'Pfister, Kurt', 'Scheuerle, Miriam C']",BMC Res Notes,,,True
a62951116b1815c48334c0caae599e4d4f06e58f,PMC,In Vitro Anti-rotaviral Activity of Achillea kellalensis,,PMC3941895,24624203,CC BY,"BACKGROUND: Achillea kellalensis, which is frequently used by Chaharmahal va Bakhtiarians residing in, Southwest of Iran, as a traditional herbal medicine for the treatment of acute diarrhea, has been selected to examine its antiviral activities against bovine rotavirus and cell toxicity activity in MA-104 cells. OBJECTIVES: The aim of this study was to evaluate the in vitro cytotoxic and anti-rotavirus properties of crude extracts of A. kellalensis. MATERIALS AND METHODS: The dried and powdered flowers of Achillea kellalensis were extracted with hot water and ethanol 50% (v/v). The cell viability and toxicity of the extracts were evaluated on MA-104 cells using four methods; trypan blue dye, NR, crystal violet and MTT assay. The in vitro anti-rotavirus properties were determined via four different assays, in order to evaluate the direct inhibition and/or the inhibition of viral replication. RESULTS: Cytotoxicity of two A. kellalensis extracts showed different concentrations. Hydro-alcoholic extract had low CC(50) at 600 µg/mL by the NR assay while the aqueous extract had high CC(50) at 1000µg/mL by the crystal violet method. In the simultaneous treatment assay and post treatment assay, the extracts were able to prevent viral replication and inhibit the viral CPE on MA-104 cells at 10 TCID(50), but the extracts did not exhibit direct antiviral activity on rotavirus adsorption. The effective concentration (EC(50)) of both extracts was observed to be 100 µg/mL. CONCLUSIONS: These results indicate that A. kellalensis extracts exert potent anti-rotaviral activity only after viral adsorption. The two extracts from A. kellalensis showed a good selectivity index. Also these results suggest that extracts prepared from the flowers of A. kellalensis may be potential anti-rotaviral agents in vivo and be useful in veterinary medicine.",2013 Aug 17,"['Taherkhani, Reza', 'Farshadpour, Fatemeh', 'Makvandi, Manoochehr']",Jundishapur J Nat Pharm Prod,,,True
7c1647ec918ab799e8f2dc782620024844c52a55,PMC,DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial,http://dx.doi.org/10.1186/1471-2431-14-37,PMC3942179,24506910,CC BY,"BACKGROUND: Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of early childhood. The objectives of this study are: 1) to compare the effect of ‘high dose’ (2000 IU/day) vs. ‘standard dose’ (400 IU/day) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children; and 2) to assess the effect of ‘high dose’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI. METHODS/DESIGN: This study is a pragmatic randomized controlled trial. Over 4 successive winters we will recruit 750 healthy children 1–5 years of age. Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be randomized to the ‘standard dose’ or ‘high dose’ oral supplemental vitamin D for a minimum of 4 months (200 children per group). Parents will obtain a nasal swab from their child with each URTI, report the number of asthma exacerbations and complete symptom checklists. Unscheduled physician visits for URTIs and asthma exacerbations will be recorded. By May, a blood sample will be drawn to determine vitamin D serum levels. The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model. Secondary analyses will compare vitamin D serum levels, asthma exacerbations and the frequency of specific viral agents between groups. DISCUSSION: Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs. This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers.",2014 Feb 8,"['Maguire, Jonathon L', 'Birken, Catherine S', 'Loeb, Mark B', 'Mamdani, Muhammad', 'Thorpe, Kevin', 'Hoch, Jeffrey S', 'Mazzulli, Tony', 'Borkhoff, Cornelia M', 'Macarthur, Colin', 'Parkin, Patricia C']",BMC Pediatr,,,True
f4abc6948ca4fa09dcedeb1fd26eefd79011d9c2,PMC,DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial,http://dx.doi.org/10.1186/1471-2431-14-37,PMC3942179,24506910,CC BY,"BACKGROUND: Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of early childhood. The objectives of this study are: 1) to compare the effect of ‘high dose’ (2000 IU/day) vs. ‘standard dose’ (400 IU/day) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children; and 2) to assess the effect of ‘high dose’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI. METHODS/DESIGN: This study is a pragmatic randomized controlled trial. Over 4 successive winters we will recruit 750 healthy children 1–5 years of age. Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be randomized to the ‘standard dose’ or ‘high dose’ oral supplemental vitamin D for a minimum of 4 months (200 children per group). Parents will obtain a nasal swab from their child with each URTI, report the number of asthma exacerbations and complete symptom checklists. Unscheduled physician visits for URTIs and asthma exacerbations will be recorded. By May, a blood sample will be drawn to determine vitamin D serum levels. The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model. Secondary analyses will compare vitamin D serum levels, asthma exacerbations and the frequency of specific viral agents between groups. DISCUSSION: Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs. This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers.",2014 Feb 8,"['Maguire, Jonathon L', 'Birken, Catherine S', 'Loeb, Mark B', 'Mamdani, Muhammad', 'Thorpe, Kevin', 'Hoch, Jeffrey S', 'Mazzulli, Tony', 'Borkhoff, Cornelia M', 'Macarthur, Colin', 'Parkin, Patricia C']",BMC Pediatr,,,False
100f1ef9121b891657828073c30b4729e7f114de,PMC,DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial,http://dx.doi.org/10.1186/1471-2431-14-37,PMC3942179,24506910,CC BY,"BACKGROUND: Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of early childhood. The objectives of this study are: 1) to compare the effect of ‘high dose’ (2000 IU/day) vs. ‘standard dose’ (400 IU/day) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children; and 2) to assess the effect of ‘high dose’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI. METHODS/DESIGN: This study is a pragmatic randomized controlled trial. Over 4 successive winters we will recruit 750 healthy children 1–5 years of age. Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be randomized to the ‘standard dose’ or ‘high dose’ oral supplemental vitamin D for a minimum of 4 months (200 children per group). Parents will obtain a nasal swab from their child with each URTI, report the number of asthma exacerbations and complete symptom checklists. Unscheduled physician visits for URTIs and asthma exacerbations will be recorded. By May, a blood sample will be drawn to determine vitamin D serum levels. The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model. Secondary analyses will compare vitamin D serum levels, asthma exacerbations and the frequency of specific viral agents between groups. DISCUSSION: Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs. This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers.",2014 Feb 8,"['Maguire, Jonathon L', 'Birken, Catherine S', 'Loeb, Mark B', 'Mamdani, Muhammad', 'Thorpe, Kevin', 'Hoch, Jeffrey S', 'Mazzulli, Tony', 'Borkhoff, Cornelia M', 'Macarthur, Colin', 'Parkin, Patricia C']",BMC Pediatr,,,False
6728e39493edf4ca2fcc3f1a94a96cb7d12e5196,PMC,DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial,http://dx.doi.org/10.1186/1471-2431-14-37,PMC3942179,24506910,CC BY,"BACKGROUND: Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of early childhood. The objectives of this study are: 1) to compare the effect of ‘high dose’ (2000 IU/day) vs. ‘standard dose’ (400 IU/day) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children; and 2) to assess the effect of ‘high dose’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI. METHODS/DESIGN: This study is a pragmatic randomized controlled trial. Over 4 successive winters we will recruit 750 healthy children 1–5 years of age. Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be randomized to the ‘standard dose’ or ‘high dose’ oral supplemental vitamin D for a minimum of 4 months (200 children per group). Parents will obtain a nasal swab from their child with each URTI, report the number of asthma exacerbations and complete symptom checklists. Unscheduled physician visits for URTIs and asthma exacerbations will be recorded. By May, a blood sample will be drawn to determine vitamin D serum levels. The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model. Secondary analyses will compare vitamin D serum levels, asthma exacerbations and the frequency of specific viral agents between groups. DISCUSSION: Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs. This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers.",2014 Feb 8,"['Maguire, Jonathon L', 'Birken, Catherine S', 'Loeb, Mark B', 'Mamdani, Muhammad', 'Thorpe, Kevin', 'Hoch, Jeffrey S', 'Mazzulli, Tony', 'Borkhoff, Cornelia M', 'Macarthur, Colin', 'Parkin, Patricia C']",BMC Pediatr,,,False
e42319fcc00ed3b44add5b145465dafbd56380b7,PMC,DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial,http://dx.doi.org/10.1186/1471-2431-14-37,PMC3942179,24506910,CC BY,"BACKGROUND: Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of early childhood. The objectives of this study are: 1) to compare the effect of ‘high dose’ (2000 IU/day) vs. ‘standard dose’ (400 IU/day) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children; and 2) to assess the effect of ‘high dose’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI. METHODS/DESIGN: This study is a pragmatic randomized controlled trial. Over 4 successive winters we will recruit 750 healthy children 1–5 years of age. Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be randomized to the ‘standard dose’ or ‘high dose’ oral supplemental vitamin D for a minimum of 4 months (200 children per group). Parents will obtain a nasal swab from their child with each URTI, report the number of asthma exacerbations and complete symptom checklists. Unscheduled physician visits for URTIs and asthma exacerbations will be recorded. By May, a blood sample will be drawn to determine vitamin D serum levels. The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model. Secondary analyses will compare vitamin D serum levels, asthma exacerbations and the frequency of specific viral agents between groups. DISCUSSION: Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs. This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers.",2014 Feb 8,"['Maguire, Jonathon L', 'Birken, Catherine S', 'Loeb, Mark B', 'Mamdani, Muhammad', 'Thorpe, Kevin', 'Hoch, Jeffrey S', 'Mazzulli, Tony', 'Borkhoff, Cornelia M', 'Macarthur, Colin', 'Parkin, Patricia C']",BMC Pediatr,,,False
ecbb9acde61473bf4f5942d6bbef461eee034a9a,PMC,DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial,http://dx.doi.org/10.1186/1471-2431-14-37,PMC3942179,24506910,CC BY,"BACKGROUND: Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of early childhood. The objectives of this study are: 1) to compare the effect of ‘high dose’ (2000 IU/day) vs. ‘standard dose’ (400 IU/day) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children; and 2) to assess the effect of ‘high dose’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI. METHODS/DESIGN: This study is a pragmatic randomized controlled trial. Over 4 successive winters we will recruit 750 healthy children 1–5 years of age. Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be randomized to the ‘standard dose’ or ‘high dose’ oral supplemental vitamin D for a minimum of 4 months (200 children per group). Parents will obtain a nasal swab from their child with each URTI, report the number of asthma exacerbations and complete symptom checklists. Unscheduled physician visits for URTIs and asthma exacerbations will be recorded. By May, a blood sample will be drawn to determine vitamin D serum levels. The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model. Secondary analyses will compare vitamin D serum levels, asthma exacerbations and the frequency of specific viral agents between groups. DISCUSSION: Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs. This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers.",2014 Feb 8,"['Maguire, Jonathon L', 'Birken, Catherine S', 'Loeb, Mark B', 'Mamdani, Muhammad', 'Thorpe, Kevin', 'Hoch, Jeffrey S', 'Mazzulli, Tony', 'Borkhoff, Cornelia M', 'Macarthur, Colin', 'Parkin, Patricia C']",BMC Pediatr,,,False
d5cc1936183d8b73aa5006487dce09b3f8fe1d65,PMC,Transcriptome Analysis of the Initial Stage of Acute WSSV Infection Caused by Temperature Change,http://dx.doi.org/10.1371/journal.pone.0090732,PMC3942461,24595043,CC BY,"White spot syndrome virus (WSSV) is the most devastating virosis threatening the shrimp culture industry worldwide. Variations of environmental factors in shrimp culture ponds usually lead to the outbreak of white spot syndrome (WSS). In order to know the molecular mechanisms of WSS outbreak induced by temperature variation and the biological changes of the host at the initial stage of WSSV acute infection, RNA-Seq technology was used to analyze the differentially expressed genes (DEGs) in shrimp with a certain amount of WSSV cultured at 18°C and shrimp whose culture temperature were raised to 25°C. To analyze whether the expression changes of the DEGs were due to temperature rising or WSSV proliferation, the expression of selected DEGs was analyzed by real-time PCR with another shrimp group, namely Group T, as control. Group T didn’t suffer WSSV infection but was subjected to temperature rising in parallel. At the initial stage of WSSV acute infection, DEGs related to energy production were up-regulated, whereas most DEGs related to cell cycle and positive regulation of cell death and were down-regulated. Triose phosphate isomerase, enolase and alcohol dehydrogenase involved in glycosis were up-regulated, while pyruvate dehydrogenase, citrate synthase and isocitrate dehydrogenase with NAD as the coenzyme involved in TCA pathway were down-regulated. Also genes involved in host DNA replication, including DNA primase, DNA topoisomerase and DNA polymerase showed down-regulated expression. Several interesting genes including crustin genes, acting binding or inhibiting protein genes, a disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) gene and a GRP 78 gene were also analyzed. Understanding the interactions between hosts and WSSV at the initial stage of acute infection will not only help to get a deep insight into the pathogenesis of WSSV but also provide clues for therapies.",2014 Mar 4,"['Sun, Yumiao', 'Li, Fuhua', 'Sun, Zheng', 'Zhang, Xiaojun', 'Li, Shihao', 'Zhang, Chengsong', 'Xiang, Jianhai']",PLoS One,,,True
6b40e3b543867aa91f5d01345cf3ed074300159c,PMC,Genome-Wide Analysis of Codon Usage and Influencing Factors in Chikungunya Viruses,http://dx.doi.org/10.1371/journal.pone.0090905,PMC3942501,24595095,CC BY,"Chikungunya virus (CHIKV) is an arthropod-borne virus of the family Togaviridae that is transmitted to humans by Aedes spp. mosquitoes. Its genome comprises a 12 kb single-strand positive-sense RNA. In the present study, we report the patterns of synonymous codon usage in 141 CHIKV genomes by calculating several codon usage indices and applying multivariate statistical methods. Relative synonymous codon usage (RSCU) analysis showed that the preferred synonymous codons were G/C and A-ended. A comparative analysis of RSCU between CHIKV and its hosts showed that codon usage patterns of CHIKV are a mixture of coincidence and antagonism. Similarity index analysis showed that the overall codon usage patterns of CHIKV have been strongly influenced by Pan troglodytes and Aedes albopictus during evolution. The overall codon usage bias was low in CHIKV genomes, as inferred from the analysis of effective number of codons (ENC) and codon adaptation index (CAI). Our data suggested that although mutation pressure dominates codon usage in CHIKV, patterns of codon usage in CHIKV are also under the influence of natural selection from its hosts and geography. To the best of our knowledge, this is first report describing codon usage analysis in CHIKV genomes. The findings from this study are expected to increase our understanding of factors involved in viral evolution, and fitness towards hosts and the environment.",2014 Mar 4,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Tong, Yigang']",PLoS One,,,True
2e83f16bbbc37d4cf2eba3dd0479e4ec7da6fc41,PMC,LBSapSal-vaccinated dogs exhibit increased circulating T-lymphocyte subsets (CD4(+) and CD8(+)) as well as a reduction of parasitism after challenge with Leishmania infantum plus salivary gland of Lutzomyia longipalpis,http://dx.doi.org/10.1186/1756-3305-7-61,PMC3943450,24507702,CC BY,"BACKGROUND: The development of a protective vaccine against canine visceral leishmaniasis (CVL) is an alternative approach for interrupting the domestic cycle of Leishmania infantum. Given the importance of sand fly salivary proteins as potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in the last few decades. In this context, we previously immunized dogs with a vaccine composed of L. braziliensis antigens plus saponin as the adjuvant and sand fly salivary gland extract (LBSapSal vaccine). This vaccine elicited an increase in both anti-saliva and anti-Leishmania IgG isotypes, higher counts of specific circulating CD8(+) T cells, and high NO production. METHODS: We investigated the immunogenicity and protective effect of LBSapSal vaccination after intradermal challenge with 1 × 10(7) late-log-phase L. infantum promastigotes in the presence of sand fly saliva of Lutzomyia longipalpis. The dogs were followed for up to 885 days after challenge. RESULTS: The LBSapSal vaccine presents extensive antigenic diversity with persistent humoral and cellular immune responses, indicating resistance against CVL is triggered by high levels of total IgG and its subtypes (IgG1 and IgG2); expansion of circulating CD5(+), CD4(+), and CD8(+) T lymphocytes and is Leishmania-specific; and reduction of splenic parasite load. CONCLUSIONS: These results encourage further study of vaccine strategies addressing Leishmania antigens in combination with proteins present in the saliva of the vector.",2014 Feb 7,"['Aguiar-Soares, Rodrigo Dian de Oliveira', 'Roatt, Bruno Mendes', 'Ker, Henrique Gama', 'Moreira, Nádia das Dores', 'Mathias, Fernando Augusto Siqueira', 'Cardoso, Jamille Mirelle de Oliveira', 'Gontijo, Nelder Figueiredo', 'Bruna-Romero, Oscar', 'Teixeira-Carvalho, Andréa', 'Martins-Filho, Olindo Assis', 'Corrêa-Oliveira, Rodrigo', 'Giunchetti, Rodolfo Cordeiro', 'Reis, Alexandre Barbosa']",Parasit Vectors,,,True
a22be780c7774b48b0f4415ed03d2e62ee098518,PMC,A Chemoinformatics Approach to the Discovery of Lead-Like Molecules from Marine and Microbial Sources En Route to Antitumor and Antibiotic Drugs,http://dx.doi.org/10.3390/md12020757,PMC3944514,24473174,CC BY,"The comprehensive information of small molecules and their biological activities in the PubChem database allows chemoinformatic researchers to access and make use of large-scale biological activity data to improve the precision of drug profiling. A Quantitative Structure–Activity Relationship approach, for classification, was used for the prediction of active/inactive compounds relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1804 compounds from PubChem. Using the best classification models for antibiotic and antitumor activities a data set of marine and microbial natural products from the AntiMarin database were screened—57 and 16 new lead compounds for antibiotic and antitumor drug design were proposed, respectively. All compounds proposed by our approach are classified as non-antibiotic and non-antitumor compounds in the AntiMarin database. Recently several of the lead-like compounds proposed by us were reported as being active in the literature.",2014 Jan 27,"['Pereira, Florbela', 'Latino, Diogo A. R. S.', 'Gaudêncio, Susana P.']",Mar Drugs,,,True
f4237ea9635b4330639d7f678c719a05f7c9d8a3,PMC,Genetic characterization of type 2a canine parvoviruses from Taiwan reveals the emergence of an Ile324 mutation in VP2,http://dx.doi.org/10.1186/1743-422X-11-39,PMC3944821,24568207,CC BY,"BACKGROUND: Canine parvovirus 2 (CPV 2) is a major infectious cause of mortality in puppies. The characteristic symptom of CPV 2 disease is intestinal hemorrhage with severe bloody diarrhea. Soon after CPV was first recognized in the late 1970s, the original virus, CPV 2, was replaced in the canine population by strains carrying minor antigenic variants (termed 2a, 2b, and 2c) of the VP2 gene that could be distinguished using monoclonal antibodies and molecular analyses. Here, we provide an updated molecular characterization of the CPV 2 circulating in Taiwan. METHODS: In this study, 28 isolates of CPV 2 from 144 dogs with suspected CPV infection were obtained from northern, central, and southern Taiwan from 2008 to 2012 and screened by PCR. The 28 isolates were sequenced, and a phylogenetic analysis of the VP2 gene was performed. RESULTS: Of the 28 Taiwanese CPV 2 isolates, 15 were identified as new CPV 2a, and 13 were identified as new CPV 2b. Compared to the reference CPV 2a, all 15 of the CPV 2a sequences collected in this study contain an Ile324 mutation caused by a TAT to ATT mutation at nucleotides 970–972 of the VP2 gene. CONCLUSION: Our VP2 sequence data revealed that both types are currently prevalent CPV 2 field strains circulating in Taiwan, and a unique Ile324 VP2 mutation was found in our Taiwanese CPV 2a isolates and recent Asian isolates. CPV 2c was not observed in this study.",2014 Feb 25,"['Lin, Chao-Nan', 'Chien, Chi-Hsien', 'Chiou, Ming-Tang', 'Chueh, Ling-Ling', 'Hung, Meng-Yu', 'Hsu, Han-Siang']",Virol J,,,True
4509a768ab8962812dbdf4c610b6d741f84c8318,PMC,Beliefs and Knowledge about Vaccination against AH1N1pdm09 Infection and Uptake Factors among Chinese Parents,http://dx.doi.org/10.3390/ijerph110201989,PMC3945580,24534766,CC BY,"Vaccination against AH1N1pdm09 infection (human swine infection, HSI) is an effective measure of preventing pandemic infection, especially for high-risk groups like children between the ages of 6 months and 6 years. This study used a cross-sectional correlation design and aimed to identify predicting factors of parental acceptance of the HSI vaccine (HSIV) and uptake of the vaccination by their preschool-aged children in Hong Kong. A total of 250 parents were recruited from four randomly selected kindergartens. A self-administered questionnaire based on the health belief framework was used for data collection. The results showed that a number of factors significantly affected the tendency toward new vaccination uptake; these factors included parental age, HSI vaccination history of the children in their family, preferable price of the vaccine, perceived severity, perceived benefits, perceived barriers, and motivating factors for taking new vaccines. Using these factors, a logistic regression model with a high Nagelkerke R(2) of 0.63 was generated to explain vaccination acceptance. A strong correlation between parental acceptance of new vaccinations and the motivating factors of vaccination uptake was found, which indicates the importance of involving parents in policy implementation for any new vaccination schemes. Overall, in order to fight against pandemics and enhance vaccination acceptance, it is essential for the government to understand the above factors determining parental acceptance of new vaccinations for their preschool-aged children.",2014 Feb 14,"['Wu, Cynthia Sau Ting', 'Kwong, Enid Wai Yung', 'Wong, Ho Ting', 'Lo, Suet Hang', 'Wong, Anthony Siu Wo']",Int J Environ Res Public Health,,,True
3ab1d505d3521db73f63ef84163a41fa2f3dbdf6,PMC,Triple Immunoglobulin Gene Knockout Transchromosomic Cattle: Bovine Lambda Cluster Deletion and Its Effect on Fully Human Polyclonal Antibody Production,http://dx.doi.org/10.1371/journal.pone.0090383,PMC3946162,24603704,CC BY,"Towards the goal of producing fully human polyclonal antibodies (hpAbs or hIgGs) in transchromosomic (Tc) cattle, we previously reported that Tc cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin (Ig) heavy-chain (hIGH), kappa-chain (hIGK), and lambda-chain (hIGL) germline loci produced physiological levels of hIgGs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, were homozygously inactivated (bIGHM(−/−), bIGHML1(−/−); double knockouts or DKO). However, because endogenous bovine immunoglobulin light chain loci are still intact, the light chains are produced both from the hIGK and hIGL genomic loci on the HAC and from the endogenous bovine kappa-chain (bIGK) and lambda-chain (bIGL) genomic loci, resulting in the production of fully hIgGs (both Ig heavy-chains and light-chains are of human origin: hIgG/hIgκ or hIgG/hIgλ) and chimeric hIgGs (Ig heavy-chains are of human origin while the Ig light-chains are of bovine origin: hIgG/bIgκ or hIgG/bIgλ). To improve fully hIgG production in Tc cattle, we here report the deletion of the entire bIGL joining (J) and constant (C) gene cluster (bIGLJ1-IGLC1 to bIGLJ5-IGLC5) by employing Cre/loxP mediated site-specific chromosome recombination and the production of triple knockout (bIGHM(−/−), bIGHML1(−/−) and bIGL(−/−); TKO) Tc cattle. We further demonstrate that bIGL cluster deletion greatly improves fully hIgGs production in the sera of TKO Tc cattle, with 51.3% fully hIgGs (hIgG/hIgκ plus hIgG/hIgλ).",2014 Mar 6,"['Matsushita, Hiroaki', 'Sano, Akiko', 'Wu, Hua', 'Jiao, Jin-an', 'Kasinathan, Poothappillai', 'Sullivan, Eddie J.', 'Wang, Zhongde', 'Kuroiwa, Yoshimi']",PLoS One,,,True
e20aef0065c509346a868a73020a7ba5862e1cd5,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,True
40711ec13cb795b87708286783e253c429380e1f,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
3b0dd174adb4bc0f1dbdb74fba9c77c87761b31c,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
1066883cb4190d7564b147d36e4bf2fcb8189a81,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
6535b5a6a1907f1e51f373a3c727a2e0765d16ce,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
967f87ec152c33fd332b2ba5ea7c76a202951eb1,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
01cb25de5152563a0654eb672d932b5605a02eb6,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
9402e240e9b4d07e6b85174891e905d254078509,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
1532ab213d617b828362ffc2050097696995fd2f,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
852ae4dbba4756ff9d7e331eb12c1672fb7ebfed,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
62d7719c3402b89f11ccb6a158dc2812f10bc234,PMC,Depletion of Alveolar Macrophages Ameliorates Virus-Induced Disease following a Pulmonary Coronavirus Infection,http://dx.doi.org/10.1371/journal.pone.0090720,PMC3946553,24608125,CC BY,"Coronaviruses cause respiratory disease in humans that can range from mild to severe. However, the pathogenesis of pulmonary coronavirus infections is poorly understood. Mouse hepatitis virus type 1 (MHV-1) is a group 2 coronavirus capable of causing severe morbidity and mortality in highly susceptible C3H/HeJ mice. We have previously shown that both CD4 and CD8 T cells play a critical role in mediating MHV-1-induced disease. Here we evaluated the role of alveolar macrophages (AM) in modulating the adaptive immune response and subsequent disease. Depletion of AM using clodronate liposomes administered prior to MHV-1 infection was associated with a significant amelioration of MHV-1-induced morbidity and mortality. AM depletion resulted in a decreased number of virus-specific CD4 T cells in the lung airways. In addition, a significant increase in the frequency and total number of Tregs in the lung tissue and lung airways was observed following MHV-1 infection in mice depleted of AM. Our results indicate that AM play a critical role in modulating MHV-1-induced morbidity and mortality.",2014 Mar 7,"['Hartwig, Stacey M.', 'Holman, Kaitlyn M.', 'Varga, Steven M.']",PLoS One,,,True
5c4dfdf8ee6230324845b917be55c47d1e991f2c,PMC,hCLE/C14orf166 Associates with DDX1-HSPC117-FAM98B in a Novel Transcription-Dependent Shuttling RNA-Transporting Complex,http://dx.doi.org/10.1371/journal.pone.0090957,PMC3946611,24608264,CC BY,"hCLE/C14orf166 is a nuclear and cytoplasmic protein that interacts with the RNAP II, modulates nuclear RNA metabolism and is present in cytoplasmic RNA granules involved in localized translation. Here we have studied whether hCLE shares common interactors in the nucleus and the cytosol, which could shed light on its participation in the sequential phases of RNA metabolism. Nuclear and cytoplasmic purified hCLE-associated factors were identified and proteins involved in mRNA metabolism, motor-related proteins, cytoskeletal and translation-related factors were found. Purified hCLE complexes also contain RNAs and as expected some hCLE-interacting proteins (DDX1, HSPC117, FAM98B) were found both in the nucleus and the cytoplasm. Moreover, endogenous hCLE fractionates in protein complexes together with DDX1, HSPC117 and FAM98B and silencing of hCLE down-regulates their nuclear and cytosolic accumulation levels. Using a photoactivatable hCLE-GFP protein, nuclear import and export of hCLE was observed indicating that hCLE is a shuttling protein. Interestingly, hCLE nuclear import required active transcription, as did the import of DDX1, HSPC117 and FAM98B proteins. The data indicate that hCLE probably as a complex with DDX1, HSPC117 and FAM98B shuttles between the nucleus and the cytoplasm transporting RNAs suggesting that this complex has a prominent role on nuclear and cytoplasmic RNA fate.",2014 Mar 7,"['Pérez-González, Alicia', 'Pazo, Alejandra', 'Navajas, Rosana', 'Ciordia, Sergio', 'Rodriguez-Frandsen, Ariel', 'Nieto, Amelia']",PLoS One,,,True
6ec1c2c2244a8d8f5959fad54ba3b7923e72e971,PMC,Intentions to Perform Non-Pharmaceutical Protective Behaviors during Influenza Outbreaks in Sweden: A Cross-Sectional Study following a Mass Vaccination Campaign,http://dx.doi.org/10.1371/journal.pone.0091060,PMC3946657,24608557,CC BY,"Failure to incorporate the beliefs and attitudes of the public into theoretical models of preparedness has been identified as a weakness in strategies to mitigate infectious disease outbreaks. We administered a cross-sectional telephone survey to a representative sample (n = 443) of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8), sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal. The interviewees were asked to make their appraisals for two scenarios: a) an influenza with low case fatality and mild lifestyle impact; b) severe influenza with high case fatality and serious disturbances of societal functions. Every second respondent (50.0%) reported high trust in official information about influenza. The proportion that reported intentions to take deliberate actions to improve personal hygiene during outbreaks ranged between 45–85%, while less than 25% said that they intended to increase social distancing. Multiple logistic regression models with coping appraisal as the explanatory factor most frequently contributing to the explanation of the variance in intentions showed strong discriminatory performance for staying home while not ill (mild outbreaks: Area under the curve [AUC] 0.85 (95% confidence interval 0.82;0.89), severe outbreaks AUC 0.82 (95% CI 0.77;0.85)) and acceptable performance with regard to avoiding public transportation (AUC 0.78 (0.74;0.82), AUC 0.77 (0.72;0.82)), using handwash products (AUC 0.70 (0.65;0.75), AUC 0.76 (0.71;0.80)), and frequently washing hands (AUC 0.71 (0.66;0.76), AUC 0.75 (0.71;0.80)). We conclude that coping appraisal was the explanatory factor most frequently included in statistical models explaining self-reported intentions to carry out non-pharmaceutical health actions in the Swedish outlined context, and that variations in threat appraisal played a smaller role in these models despite scientific uncertainties surrounding a recent mass vaccination campaign.",2014 Mar 7,"['Timpka, Toomas', 'Spreco, Armin', 'Gursky, Elin', 'Eriksson, Olle', 'Dahlström, Örjan', 'Strömgren, Magnus', 'Ekberg, Joakim', 'Pilemalm, Sofie', 'Karlsson, David', 'Hinkula, Jorma', 'Holm, Einar']",PLoS One,,,True
2318d71622cd266fdbd9a9d80f25e689ff6f61ae,PMC,Detection of Viral Proteins in Human Cells Lines by Xeno-Proteomics: Elimination of the Last Valid Excuse for Not Testing Every Cellular Proteome Dataset for Viral Proteins,http://dx.doi.org/10.1371/journal.pone.0091433,PMC3950186,24618588,CC BY,"Cell cultures used routinely in proteomic experiments may contain proteins from other species because of infection, transfection or just contamination. Since infection or contamination may affect the results of a biological experiment, it is important to test the samples for the presence of “alien” proteins. Usually cells are tested only for the most common infections, and most of the existing tests are targeting specific contaminations. Here we describe a three-step procedure for reliable untargeted detection of viral proteins using proteomics data, and recommend this or similar procedure to be applied to every proteomics dataset submitted for publication.",2014 Mar 11,"['Chernobrovkin, Alexey L.', 'Zubarev, Roman A.']",PLoS One,,,True
da9d1b5baf44c1abc7fa6b9e3f99f2de27f1a7c4,PMC,Detection of Viral Proteins in Human Cells Lines by Xeno-Proteomics: Elimination of the Last Valid Excuse for Not Testing Every Cellular Proteome Dataset for Viral Proteins,http://dx.doi.org/10.1371/journal.pone.0091433,PMC3950186,24618588,CC BY,"Cell cultures used routinely in proteomic experiments may contain proteins from other species because of infection, transfection or just contamination. Since infection or contamination may affect the results of a biological experiment, it is important to test the samples for the presence of “alien” proteins. Usually cells are tested only for the most common infections, and most of the existing tests are targeting specific contaminations. Here we describe a three-step procedure for reliable untargeted detection of viral proteins using proteomics data, and recommend this or similar procedure to be applied to every proteomics dataset submitted for publication.",2014 Mar 11,"['Chernobrovkin, Alexey L.', 'Zubarev, Roman A.']",PLoS One,,,False
c0617473da97a9dd36b02d46fe80b144f2138f0a,PMC,Cellular trafficking determines the exon skipping activity of Pip6a-PMO in mdx skeletal and cardiac muscle cells,http://dx.doi.org/10.1093/nar/gkt1220,PMC3950666,24366877,CC BY,"Cell-penetrating peptide-mediated delivery of phosphorodiamidate morpholino oligomers (PMOs) has shown great promise for exon-skipping therapy of Duchenne Muscular Dystrophy (DMD). Pip6a-PMO, a recently developed conjugate, is particularly efficient in a murine DMD model, although mechanisms responsible for its increased biological activity have not been studied. Here, we evaluate the cellular trafficking and the biological activity of Pip6a-PMO in skeletal muscle cells and primary cardiomyocytes. Our results indicate that Pip6a-PMO is taken up in the skeletal muscle cells by an energy- and caveolae-mediated endocytosis. Interestingly, its cellular distribution is different in undifferentiated and differentiated skeletal muscle cells (vesicular versus nuclear). Likewise, Pip6a-PMO mainly accumulates in cytoplasmic vesicles in primary cardiomyocytes, in which clathrin-mediated endocytosis seems to be the pre-dominant uptake pathway. These differences in cellular trafficking correspond well with the exon-skipping data, with higher activity in myotubes than in myoblasts or cardiomyocytes. These differences in cellular trafficking thus provide a possible mechanistic explanation for the variations in exon-skipping activity and restoration of dystrophin protein in heart muscle compared with skeletal muscle tissues in DMD models. Overall, Pip6a-PMO appears as the most efficient conjugate to date (low nanomolar EC(50)), even if limitations remain from endosomal escape.",2014 Mar 22,"['Lehto, Taavi', 'Castillo Alvarez, Alejandra', 'Gauck, Sarah', 'Gait, Michael J.', 'Coursindel, Thibault', 'Wood, Matthew J. A.', 'Lebleu, Bernard', 'Boisguerin, Prisca']",Nucleic Acids Res,,,True
b1f90c0a862d8dc3485d61deb8c87c0b53b798b8,PMC,"Hantaan Virus Infection Induces CXCL10 Expression through TLR3, RIG-I, and MDA-5 Pathways Correlated with the Disease Severity",http://dx.doi.org/10.1155/2014/697837,PMC3950924,24701034,CC BY,"Hantaan virus (HTNV) is a major agent causing hemorrhagic fever with renal syndrome (HFRS). Although the pathogenesis of HFRS is unclear, some reports have suggested that the abundant production of proinflammatory cytokines and uncontrolled inflammatory responses may contribute to the development of HFRS. CXCL10 is one of these cytokines and is found to be involved in the pathogenesis of many virus infectious diseases. However, the role of CXCL10 in the pathogenesis of HFRS and the molecular regulation mechanism of CXCL10 in HTNV infection remain unknown. In this study, we report that CXCL10 expresses highly in the HFRS patients' sera and the elevated CXCL10 is positively correlated with the severity of HFRS. We find that HTNV, a single-strand RNA virus, can act as a double-strand RNA to activate the TLR3, RIG-I, and MDA-5 signaling pathways. Through the downstream transcription factors of these pathways, NF-κB and IRF7, which bind directly to the CXCL10's promoter, the expression of CXCL10 is increased. Our results may help to better understand the role of CXCL10 in the development of HFRS and may provide some novel insights into the immune response of HTNV infection.",2014 Feb 23,"['Zhang, Yusi', 'Liu, Bei', 'Ma, Ying', 'Yi, Jing', 'Zhang, Chunmei', 'Zhang, Yun', 'Xu, Zhuwei', 'Wang, Jiuping', 'Yang, Kun', 'Yang, Angang', 'Zhuang, Ran', 'Jin, Boquan']",Mediators Inflamm,,,True
f5ad2323eb387f6e271e2842bb2cc4a33504fde3,PMC,In Vitro Antiviral Activity of Circular Triple Helix Forming Oligonucleotide RNA towards Feline Infectious Peritonitis Virus Replication,http://dx.doi.org/10.1155/2014/654712,PMC3950953,24707494,CC BY,"Feline Infectious Peritonitis (FIP) is a severe fatal immune-augmented disease in cat population. It is caused by FIP virus (FIPV), a virulent mutant strain of Feline Enteric Coronavirus (FECV). Current treatments and prophylactics are not effective. The in vitro antiviral properties of five circular Triple-Helix Forming Oligonucleotide (TFO) RNAs (TFO1 to TFO5), which target the different regions of virulent feline coronavirus (FCoV) strain FIPV WSU 79-1146 genome, were tested in FIPV-infected Crandell-Rees Feline Kidney (CRFK) cells. RT-qPCR results showed that the circular TFO RNAs, except TFO2, inhibit FIPV replication, where the viral genome copy numbers decreased significantly by 5-fold log(10) from 10(14) in the virus-inoculated cells to 10(9) in the circular TFO RNAs-transfected cells. Furthermore, the binding of the circular TFO RNA with the targeted viral genome segment was also confirmed using electrophoretic mobility shift assay. The strength of binding kinetics between the TFO RNAs and their target regions was demonstrated by NanoITC assay. In conclusion, the circular TFOs have the potential to be further developed as antiviral agents against FIPV infection.",2014 Feb 20,"['Choong, Oi Kuan', 'Mehrbod, Parvaneh', 'Tejo, Bimo Ario', 'Omar, Abdul Rahman']",Biomed Res Int,,,True
772e7c8efc8fed6e7c27602dc255fd97f2f55a7e,PMC,China Tuberculosis Policy at Crucial Crossroads: Comparing the Practice of Different Hospital and Tuberculosis Control Collaboration Models Using Survey Data,http://dx.doi.org/10.1371/journal.pone.0090596,PMC3951218,24621996,CC BY,"BACKGROUND: Currently three hospital and tuberculosis (TB) collaboration models exist in China: the dispensary model where TB has to be diagnosed and treated in TB dispensaries, the specialist model where TB specialist hospital also treat TB patients, and the integrated model where TB diagnosis and treatment is integrated into a general hospital. The study compared effects of the three models through exploring patient experience in TB diagnosis and treatment. METHODS: We selected two sites in each model of TB service in four provinces of China. In each site, 50 patients were selected from TB patient registries for a structured questionnaire survey, with a total of 293 patients recruited. All participants were newly registered uncomplicated TB cases without any major complications or resistance to first-line anti-TB drugs, and having successfully completed treatment. Diagnostic and treatment procedures were reviewed from medical charts of the surveyed patients to compare with national guidelines. RESULTS: Specialist sites had the highest patient expenditure, hospitalization rates and mostly used second-line anti-TB drugs, while the integrated model reported the opposite. The median health expenditure was USD 1,499 for the specialist sites and USD 306 for the integrated sites, with 83% and 15% patients respectively having unnecessary hospitalization. 74% of the specialist sites and 19% of the integrated sites used second-line anti-TB drugs. Mixed results were identified in the two dispensary sites. One site had median health expenditure of USD 138 with 12% of patients hospitalized, while the other had USD 912 and 65% respectively. CONCLUSION: The study observed prohibitive financial expenditure and a high level of deviation from national guidelines in all sites, which may be related to the profit-seeking behavior of public hospitals. The study supports the integrated model as the better policy option for future TB health reform in China.",2014 Mar 12,"['Wei, Xiaolin', 'Zou, Guanyang', 'Walley, John', 'Yin, Jia', 'Lonnroth, Knut', 'Uplekar, Mukund', 'Wang, Weibing', 'Sun, Qiang']",PLoS One,,,True
832fab67c299fb2682948d33858e58a5db71e6f8,PMC,A Novel Vaccine against Crimean-Congo Haemorrhagic Fever Protects 100% of Animals against Lethal Challenge in a Mouse Model,http://dx.doi.org/10.1371/journal.pone.0091516,PMC3951450,24621656,CC BY,"Crimean-Congo Haemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. Between 15–70% of reported cases are fatal. There is no approved vaccine available, and preclinical protection in vivo by an experimental vaccine has not been demonstrated previously. In the present study, the attenuated poxvirus vector, Modified Vaccinia virus Ankara, was used to develop a recombinant candidate vaccine expressing the CCHF virus glycoproteins. Cellular and humoral immunogenicity was confirmed in two mouse strains, including type I interferon receptor knockout mice, which are susceptible to CCHF disease. This vaccine protected all recipient animals from lethal disease in a challenge model adapted to represent infection via a tick bite. Histopathology and viral load analysis of protected animals confirmed that they had been exposed to challenge virus, even though they did not exhibit clinical signs. This is the first demonstration of efficacy of a CCHF vaccine.",2014 Mar 12,"['Buttigieg, Karen R.', 'Dowall, Stuart D.', 'Findlay-Wilson, Stephen', 'Miloszewska, Aleksandra', 'Rayner, Emma', 'Hewson, Roger', 'Carroll, Miles W.']",PLoS One,,,True
b4b8196a56fe00d653d288226f12952824c5b7cc,PMC,Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned,http://dx.doi.org/10.3389/fncel.2014.00073,PMC3952085,24659953,CC BY,"Although astrogliosis and microglia activation are characteristic features of multiple sclerosis (MS) and other central nervous system (CNS) lesions the exact functions of these events are not fully understood. Animal models help to understand the complex interplay between the different cell types of the CNS and uncover general mechanisms of damage and repair of myelin sheaths. The so called cuprizone model is a toxic model of demyelination in the CNS white and gray matter, which lacks an autoimmune component. Cuprizone induces apoptosis of mature oligodendrocytes that leads to a robust demyelination and profound activation of both astrocytes and microglia with regional heterogeneity between different white and gray matter regions. Although not suitable to study autoimmune mediated demyelination, this model is extremely helpful to elucidate basic cellular and molecular mechanisms during de- and particularly remyelination independently of interactions with peripheral immune cells. Phagocytosis and removal of damaged myelin seems to be one of the major roles of microglia in this model and it is well known that removal of myelin debris is a prerequisite of successful remyelination. Furthermore, microglia provide several signals that support remyelination. The role of astrocytes during de- and remyelination is not well defined. Both supportive and destructive functions have been suggested. Using the cuprizone model we could demonstrate that there is an important crosstalk between astrocytes and microglia. In this review we focus on the role of glial reactions and interaction in the cuprizone model. Advantages and limitations of as well as its potential therapeutic relevance for the human disease MS are critically discussed in comparison to other animal models.",2014 Mar 13,"['Gudi, Viktoria', 'Gingele, Stefan', 'Skripuletz, Thomas', 'Stangel, Martin']",Front Cell Neurosci,,,True
879b0904d411e88c1be90f0660e7bb4377ae29d8,PMC,Porcine epidemic diarrhea virus (PEDV) co-infection induced chlamydial persistence/stress does not require viral replication,http://dx.doi.org/10.3389/fcimb.2014.00020,PMC3952398,24660163,CC BY,"Chlamydiae may exist at the site of infection in an alternative replicative form, called the aberrant body (AB). ABs are produced during a viable but non-infectious developmental state termed “persistence” or “chlamydial stress.” As persistent/stressed chlamydiae: (i) may contribute to chronic inflammation observed in diseases like trachoma; and (ii) are more resistant to current anti-chlamydial drugs of choice, it is critical to better understand this developmental stage. We previously demonstrated that porcine epidemic diarrhea virus (PEDV) co-infection induced Chlamydia pecorum persistence/stress in culture. One critical characteristic of persistence/stress is that the chlamydiae remain viable and can reenter the normal developmental cycle when the stressor is removed. Thus, we hypothesized that PEDV-induced persistence would be reversible if viral replication was inhibited. Therefore, we performed time course experiments in which Vero cells were C. pecorum/PEDV infected in the presence of cycloheximide (CHX), which inhibits viral but not chlamydial protein synthesis. CHX-exposure inhibited PEDV replication, but did not inhibit induction of C. pecorum persistence at 24 h post-PEDV infection, as indicated by AB formation and reduced production of infectious EBs. Interestingly, production of infectious EBs resumed when CHX-exposed, co-infected cells were incubated 48–72 h post-PEDV co-infection. These data demonstrate that PEDV co-infection-induced chlamydial persistence/stress is reversible and suggest that this induction (i) does not require viral replication in host cells; and (ii) does not require de novo host or viral protein synthesis. These data also suggest that viral binding and/or entry may be required for this effect. Because the PEDV host cell receptor (CD13 or aminopeptidase N) stimulates cellular signaling pathways in the absence of PEDV infection, we suspect that PEDV co-infection might alter CD13 function and induce the chlamydiae to enter the persistent state.",2014 Mar 13,"['Schoborg, Robert V.', 'Borel, Nicole']",Front Cell Infect Microbiol,,,True
be45cd588caaa0d8e5cdcd0cb7a1a59ccfc85d51,PMC,Enhancement of accuracy and efficiency for RNA secondary structure prediction by sequence segmentation and MapReduce,http://dx.doi.org/10.1186/1472-6807-13-S1-S3,PMC3952952,24564983,CC BY,"BACKGROUND: Ribonucleic acid (RNA) molecules play important roles in many biological processes including gene expression and regulation. Their secondary structures are crucial for the RNA functionality, and the prediction of the secondary structures is widely studied. Our previous research shows that cutting long sequences into shorter chunks, predicting secondary structures of the chunks independently using thermodynamic methods, and reconstructing the entire secondary structure from the predicted chunk structures can yield better accuracy than predicting the secondary structure using the RNA sequence as a whole. The chunking, prediction, and reconstruction processes can use different methods and parameters, some of which produce more accurate predictions than others. In this paper, we study the prediction accuracy and efficiency of three different chunking methods using seven popular secondary structure prediction programs that apply to two datasets of RNA with known secondary structures, which include both pseudoknotted and non-pseudoknotted sequences, as well as a family of viral genome RNAs whose structures have not been predicted before. Our modularized MapReduce framework based on Hadoop allows us to study the problem in a parallel and robust environment. RESULTS: On average, the maximum accuracy retention values are larger than one for our chunking methods and the seven prediction programs over 50 non-pseudoknotted sequences, meaning that the secondary structure predicted using chunking is more similar to the real structure than the secondary structure predicted by using the whole sequence. We observe similar results for the 23 pseudoknotted sequences, except for the NUPACK program using the centered chunking method. The performance analysis for 14 long RNA sequences from the Nodaviridae virus family outlines how the coarse-grained mapping of chunking and predictions in the MapReduce framework exhibits shorter turnaround times for short RNA sequences. However, as the lengths of the RNA sequences increase, the fine-grained mapping can surpass the coarse-grained mapping in performance. CONCLUSIONS: By using our MapReduce framework together with statistical analysis on the accuracy retention results, we observe how the inversion-based chunking methods can outperform predictions using the whole sequence. Our chunk-based approach also enables us to predict secondary structures for very long RNA sequences, which is not feasible with traditional methods alone.",2013 Nov 8,"['Zhang, Boyu', 'Yehdego, Daniel T', 'Johnson, Kyle L', 'Leung, Ming-Ying', 'Taufer, Michela']",BMC Struct Biol,,,True
5da136317f5b97ed8371d5121d8828f1c9a5372d,PMC,Congenital Malaria in China,http://dx.doi.org/10.1371/journal.pntd.0002622,PMC3953009,24626148,CC BY,"ABSTRACT: BACKGROUND: Congenital malaria, in which infants are directly infected with malaria parasites from their mother prior to or during birth, is a potentially life-threatening condition that occurs at relatively low rates in malaria-endemic regions. It is recognized as a serious problem in Plasmodium falciparum–endemic sub-Saharan Africa, where recent data suggests that it is more common than previously believed. In such regions where malaria transmission is high, neonates may be protected from disease caused by congenital malaria through the transfer of maternal antibodies against the parasite. However, in low P. vivax–endemic regions, immunity to vivax malaria is low; thus, there is the likelihood that congenital vivax malaria poses a more significant threat to newborn health. Malaria had previously been a major parasitic disease in China, and congenital malaria case reports in Chinese offer valuable information for understanding the risks posed by congenital malaria to neonatal health. As most of the literature documenting congenital malaria cases in China are written in Chinese and therefore are not easily accessible to the global malaria research community, we have undertaken an extensive review of the Chinese literature on this subject. METHODS/PRINCIPAL FINDINGS: Here, we reviewed congenital malaria cases from three major searchable Chinese journal databases, concentrating on data from 1915 through 2011. Following extensive screening, a total of 104 cases of congenital malaria were identified. These cases were distributed mainly in the eastern, central, and southern regions of China, as well as in the low-lying region of southwest China. The dominant species was P. vivax (92.50%), reflecting the malaria parasite species distribution in China. The leading clinical presentation was fever, and other clinical presentations were anaemia, jaundice, paleness, diarrhoea, vomiting, and general weakness. With the exception of two cases, all patients were cured with antimalarial drugs such as chloroquine, quinine, artemether, and artesunate. CONCLUSIONS: The symptoms of congenital malaria vary significantly between cases, so clear and early diagnosis is difficult. We suggest that active surveillance might be necessary for neonates born to mothers with a history of malaria.",2014 Mar 13,"['Tao, Zhi-yong', 'Fang, Qiang', 'Liu, Xue', 'Culleton, Richard', 'Tao, Li', 'Xia, Hui', 'Gao, Qi']",PLoS Negl Trop Dis,,,True
0f6b1645fdc27b32ae9fdb4f99dbbb30eb1dfd7f,PMC,Dengue Virus Type 2 (DENV2)-Induced Oxidative Responses in Monocytes from Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient and G6PD Normal Subjects,http://dx.doi.org/10.1371/journal.pntd.0002711,PMC3953068,24625456,CC BY,"BACKGROUND: Dengue virus is endemic in peninsular Malaysia. The clinical manifestations vary depending on the incubation period of the virus as well as the immunity of the patients. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is prevalent in Malaysia where the incidence is 3.2%. It has been noted that some G6PD-deficient individuals suffer from more severe clinical presentation of dengue infection. In this study, we aim to investigate the oxidative responses of DENV2-infected monocytes from G6PD-deficient individuals. METHODOLOGY: Monocytes from G6PD-deficient individuals were infected with DENV2 and infection rate, levels of oxidative species, nitric oxide (NO), superoxide anions (O(2) (−)), and oxidative stress were determined and compared with normal controls. PRINCIPAL FINDINGS: Monocytes from G6PD-deficient individuals exhibited significantly higher infection rates compared to normal controls. In an effort to explain the reason for this enhanced susceptibility, we investigated the production of NO and O(2) (−) in the monocytes of individuals with G6PD deficiency compared with normal controls. We found that levels of NO and O(2) (−) were significantly lower in the DENV-infected monocytes from G6PD-deficient individuals compared with normal controls. Furthermore, the overall oxidative stress in DENV-infected monocytes from G6PD-deficient individuals was significantly higher when compared to normal controls. Correlation studies between DENV-infected cells and oxidative state of monocytes further confirmed these findings. CONCLUSIONS/SIGNIFICANCE: Altered redox state of DENV-infected monocytes from G6PD-deficient individuals appears to augment viral replication in these cells. DENV-infected G6PD-deficient individuals may contain higher viral titers, which may be significant in enhanced virus transmission. Furthermore, granulocyte dysfunction and higher viral loads in G6PD-deificient individuals may result in severe form of dengue infection.",2014 Mar 13,"['Al-alimi, Abdullah Ahmed', 'Ali, Syed A.', 'Al-Hassan, Faisal Muti', 'Idris, Fauziah Mohd', 'Teow, Sin-Yeang', 'Mohd Yusoff, Narazah']",PLoS Negl Trop Dis,,,True
d964ce1c8dd79290032b1b70d511f256b805e558,PMC,Adaptive Gene Amplification As an Intermediate Step in the Expansion of Virus Host Range,http://dx.doi.org/10.1371/journal.ppat.1004002,PMC3953438,24626510,CC BY,"The majority of recently emerging infectious diseases in humans is due to cross-species pathogen transmissions from animals. To establish a productive infection in new host species, viruses must overcome barriers to replication mediated by diverse and rapidly evolving host restriction factors such as protein kinase R (PKR). Many viral antagonists of these restriction factors are species specific. For example, the rhesus cytomegalovirus PKR antagonist, RhTRS1, inhibits PKR in some African green monkey (AGM) cells, but does not inhibit human or rhesus macaque PKR. To model the evolutionary changes necessary for cross-species transmission, we generated a recombinant vaccinia virus that expresses RhTRS1 in a strain that lacks PKR inhibitors E3L and K3L (VVΔEΔK+RhTRS1). Serially passaging VVΔEΔK+RhTRS1 in minimally-permissive AGM cells increased viral replication 10- to 100-fold. Notably, adaptation in these AGM cells also improved virus replication 1000- to 10,000-fold in human and rhesus cells. Genetic analyses including deep sequencing revealed amplification of the rhtrs1 locus in the adapted viruses. Supplying additional rhtrs1 in trans confirmed that amplification alone was sufficient to improve VVΔEΔK+RhTRS1 replication. Viruses with amplified rhtrs1 completely blocked AGM PKR, but only partially blocked human PKR, consistent with the replication properties of these viruses in AGM and human cells. Finally, in contrast to AGM-adapted viruses, which could be serially propagated in human cells, VVΔEΔK+RhTRS1 yielded no progeny virus after only three passages in human cells. Thus, rhtrs1 amplification in a minimally permissive intermediate host was a necessary step, enabling expansion of the virus range to previously nonpermissive hosts. These data support the hypothesis that amplification of a weak viral antagonist may be a general evolutionary mechanism to permit replication in otherwise resistant host species, providing a molecular foothold that could enable further adaptations necessary for efficient replication in the new host.",2014 Mar 13,"['Brennan, Greg', 'Kitzman, Jacob O.', 'Rothenburg, Stefan', 'Shendure, Jay', 'Geballe, Adam P.']",PLoS Pathog,,,True
8a096b3f838ccc2fab01f191ea2aacd2005f3f68,PMC,Epidemics in Partially Overlapped Multiplex Networks,http://dx.doi.org/10.1371/journal.pone.0092200,PMC3954885,24632709,CC BY,"Many real networks exhibit a layered structure in which links in each layer reflect the function of nodes on different environments. These multiple types of links are usually represented by a multiplex network in which each layer has a different topology. In real-world networks, however, not all nodes are present on every layer. To generate a more realistic scenario, we use a generalized multiplex network and assume that only a fraction [Image: see text] of the nodes are shared by the layers. We develop a theoretical framework for a branching process to describe the spread of an epidemic on these partially overlapped multiplex networks. This allows us to obtain the fraction of infected individuals as a function of the effective probability that the disease will be transmitted [Image: see text]. We also theoretically determine the dependence of the epidemic threshold on the fraction [Image: see text] of shared nodes in a system composed of two layers. We find that in the limit of [Image: see text] the threshold is dominated by the layer with the smaller isolated threshold. Although a system of two completely isolated networks is nearly indistinguishable from a system of two networks that share just a few nodes, we find that the presence of these few shared nodes causes the epidemic threshold of the isolated network with the lower propagating capacity to change discontinuously and to acquire the threshold of the other network.",2014 Mar 14,"['Buono, Camila', 'Alvarez-Zuzek, Lucila G.', 'Macri, Pablo A.', 'Braunstein, Lidia A.']",PLoS One,,,True
f7735a5236aeba514810bd4538357cb4f4e09fce,PMC,Differential Host Cell Gene Expression and Regulation of Cell Cycle Progression by Nonstructural Protein 11 of Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1155/2014/430508,PMC3955671,24719865,CC BY,"Nonstructural protein 11 (nsp11) of porcine reproductive and respiratory syndrome virus (PRRSV) is a viral endoribonuclease with an unknown function. The regulation of cellular gene expression by nsp11 was examined by RNA microarrays using MARC-nsp11 cells constitutively expressing nsp11. In these cells, the interferon-β, interferon regulatory factor 3, and nuclear factor-κB activities were suppressed compared to those of parental cells, suggesting that nsp11 might serve as a viral interferon antagonist. Differential cellular transcriptome was examined using Affymetrix exon chips representing 28,536 transcripts, and after statistical analyses 66 cellular genes were shown to be upregulated and 104 genes were downregulated by nsp11. These genes were grouped into 5 major signaling pathways according to their functional relations: histone-related, cell cycle and DNA replication, mitogen activated protein kinase signaling, complement, and ubiquitin-proteasome pathways. Of these, the modulation of cell cycle by nsp11 was further investigated since many of the regulated genes fell in this particular pathway. Flow cytometry showed that nsp11 caused the delay of cell cycle progression at the S phase and the BrdU staining confirmed the cell cycle arrest in nsp11-expressing cells. The study provides insights into the understanding of specific cellular responses to nsp11 during PRRSV infection.",2014 Feb 26,"['Sun, Yan', 'Li, Dong', 'Giri, Sumanprava', 'Prasanth, Supriya G.', 'Yoo, Dongwan']",Biomed Res Int,,,True
de925d6c5bc669b0ada19aedaf299dfaed7445ad,PMC,Migration and health in Southern Africa: 100 years and still circulating,http://dx.doi.org/10.1080/21642850.2013.866898,PMC3956074,24653964,CC BY,"Migration has deep historical roots in South and Southern Africa and to this day continues to be highly prevalent and a major factor shaping South African society and health. In this paper we examine the role of migration in the spread of two diseases nearly 100 years apart: tuberculosis following the discovery of gold in 1886 and HIV in the early 1990s. Both cases demonstrate the critical role played by human migration in the transmission and subsequent dissemination of these diseases to rural areas. In both cases, migration acts to assemble in one high-risk environment thousands of young men highly susceptible to new diseases. With poor living and working conditions, these migration destinations act as hot-spots for disease transmission. Migration of workers back to rural areas then serves as a highly efficient means of disseminating these diseases to rural populations. We conclude by raising some more recent questions examining the current role of migration in Southern Africa.",2014 Jan 1,"['Lurie, Mark N.', 'Williams, Brian G.']",Health Psychol Behav Med,,,True
dcb83fc0259abca0186d62b0b1d32eaf8607fcfc,PMC,Gene Silencing of SOCS3 by siRNA Intranasal Delivery Inhibits Asthma Phenotype in Mice,http://dx.doi.org/10.1371/journal.pone.0091996,PMC3956882,24637581,CC BY,"Suppresors of cytokine signaling (SOCS) proteins regulate cytokine responses and control immune balance. Several studies have confirmed that SOCS3 is increased in asthmatic patients, and SOCS3 expression is correlated with disease severity. The objective of this study was to evaluate if delivering of SOCS3 short interfering RNA (siRNA) intranasally in lungs could be a good therapeutic approach in an asthma chronic mouse model. Our results showed that intranasal treatment with SOCS3-siRNA led to an improvement in the eosinophil count and the normalization of hyperresponsiveness to methacholine. Concomitantly, this treatment resulted in an improvement in mucus secretion, a reduction in lung collagen, which are prominent features of airway remodeling. The mechanism implies JAK/STAT and RhoA/Rho-kinase signaling pathway, because we found a decreasing in STAT3 phosphorylation status and down regulation of RhoA/Rho-kinase protein expression. These results might lead to a new therapy for the treatment of chronic asthma.",2014 Mar 17,"[None, 'Mazzeo, Carla', 'Gámez, Cristina', 'Rodriguez Marco, Ainara', 'de Zulueta, Ana', 'Sanz, Veronica', 'Bilbao, Izaskun', 'Ruiz-Cabello, Jesús', 'Zubeldia, Jose M.', 'del Pozo, Victoria']",PLoS One,,,True
3159f6ba739648bbaa0b8b7eb498924a8d21cf8e,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,True
00378829b1df524d9f72cdad968dc635c614fa41,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
9a306ee64f21422e00a4b55bd1cec04d2d35a836,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
b7f569585aafded757463cd95eeb68534001841f,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
449ffbcc271a7f0606d6d6e1db69d135e82cebff,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
ea5e91fad311e440b03ace589789841ecb0d3d8d,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
fd314c9703b75474ea7a9cd80acd8edb028eda3d,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
7489c191e0bb82790ad2be5b708e0f49e0ba0332,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
5d5256f8f520d9752d5fef8425df87d7a953cde0,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
20a618f5cb2d18add9852731a45e81d2404f346b,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
517c73d7a87c11b3a643f609c9ceee95b5432581,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
7c608e69084d51e22aba905364bc88ff2819698f,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
3e77bba0df6bcecc06f68cb14627737ed8f747d3,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
6523295fccf833aa2e20ecf80196ea7fbd82b043,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
5753df8ed90cfb059e39566ad1271587df4ad31d,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
8a729774a87e5a4a908a85e01b24ca6882e7c2f8,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
87258f75b4634f185e7062cae7628e27f83a6dcc,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
ae7e947ef8f28c4a5f1ee201cf0c2d6cd54a40d8,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
1bc2878023734630f4bfdf86bf62b0bdeebc7d7b,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
59013a7b62d641a9e14cabe90fcda41a52870772,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
4126632a4e57a806d8da05023850ba8755cf802f,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
f7a1f8ff3552ac192d882ad7ef31d46c21ca1e32,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,True
990153e74de3d5bc506c686afb5dbf037cfa5d6b,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
810ff7a21410bfe51bc95f54e9bfdb922d9ef848,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
fb4c3d10a9ea514f135f1fdbc5b535bd7955d888,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
3282216c38dff96f0fa23f520317ad7572fa1da2,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
1d960a741888ae2ee9c8a7ea154c651de9cbd272,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
11da1c0cfae7699891514093f0695df560e4fc99,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
fc86da0d534cd666f77d946c63a8cea739111283,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
48c4de8366001c46339033536193b44103ee7f96,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
ac2a2ff57637dadf2e51cc82b4ef561765b715c9,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
5fa8a1eb8fab8c225ab28402700a6c3aa950f2d6,PMC,DBatVir: the database of bat-associated viruses,http://dx.doi.org/10.1093/database/bau021,PMC3958617,24647629,CC BY,"Emerging infectious diseases remain a significant threat to public health. Most emerging infectious disease agents in humans are of zoonotic origin. Bats are important reservoir hosts of many highly lethal zoonotic viruses and have been implicated in numerous emerging infectious disease events in recent years. It is essential to enhance our knowledge and understanding of the genetic diversity of the bat-associated viruses to prevent future outbreaks. To facilitate further research, we constructed the database of bat-associated viruses (DBatVir). Known viral sequences detected in bat samples were manually collected and curated, along with the related metadata, such as the sampling time, location, bat species and specimen type. Additional information concerning the bats, including common names, diet type, geographic distribution and phylogeny were integrated into the database to bridge the gap between virologists and zoologists. The database currently covers >4100 bat-associated animal viruses of 23 viral families detected from 196 bat species in 69 countries worldwide. It provides an overview and snapshot of the current research regarding bat-associated viruses, which is essential now that the field is rapidly expanding. With a user-friendly interface and integrated online bioinformatics tools, DBatVir provides a convenient and powerful platform for virologists and zoologists to analyze the virome diversity of bats, as well as for epidemiologists and public health researchers to monitor and track current and future bat-related infectious diseases. Database URL: http://www.mgc.ac.cn/DBatVir/",2014 Mar 18,"['Chen, Lihong', 'Liu, Bo', 'Yang, Jian', 'Jin, Qi']",Database (Oxford),,,True
e80ffcae95f83bc7e4353e746ec75187eb61281e,PMC,Multistep-Ahead Air Passengers Traffic Prediction with Hybrid ARIMA-SVMs Models,http://dx.doi.org/10.1155/2014/567246,PMC3958729,24723814,CC BY,"The hybrid ARIMA-SVMs prediction models have been established recently, which take advantage of the unique strength of ARIMA and SVMs models in linear and nonlinear modeling, respectively. Built upon this hybrid ARIMA-SVMs models alike, this study goes further to extend them into the case of multistep-ahead prediction for air passengers traffic with the two most commonly used multistep-ahead prediction strategies, that is, iterated strategy and direct strategy. Additionally, the effectiveness of data preprocessing approaches, such as deseasonalization and detrending, is investigated and proofed along with the two strategies. Real data sets including four selected airlines' monthly series were collected to justify the effectiveness of the proposed approach. Empirical results demonstrate that the direct strategy performs better than iterative one in long term prediction case while iterative one performs better in the case of short term prediction. Furthermore, both deseasonalization and detrending can significantly improve the prediction accuracy for both strategies, indicating the necessity of data preprocessing. As such, this study contributes as a full reference to the planners from air transportation industries on how to tackle multistep-ahead prediction tasks in the implementation of either prediction strategy.",2014 Feb 27,"['Ming, Wei', 'Bao, Yukun', 'Hu, Zhongyi', 'Xiong, Tao']",ScientificWorldJournal,,,True
b3e94bce63878a41d45d22c012a9492d079b3b7f,PMC,NTCP and Beyond: Opening the Door to Unveil Hepatitis B Virus Entry,http://dx.doi.org/10.3390/ijms15022892,PMC3958888,24557582,CC BY,"Chronic hepatitis B virus (HBV) infection, affecting approximately 240 million people worldwide, is a major public health problem that elevates the risk of developing liver cirrhosis and hepatocellular carcinoma. Given that current anti-HBV drugs are limited to interferon-based regimens and nucleos(t)ide analogs, the development of new anti-HBV agents is urgently needed. The viral entry process is generally an attractive target implicated in antiviral strategies. Using primary cells from humans and Tupaia belangeri, as well as HepaRG cells, important determinants of viral entry have been achieved. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was identified as an HBV entry receptor and enabled the establishment of a susceptible cell line that can efficiently support HBV infection. This finding will allow a deeper understanding of the requirements for efficient HBV infection, including the elucidation of the molecular entry mechanism. In addition, pharmacological studies suggest that NTCP is able to serve as a therapeutic target. This article summarizes our current knowledge on the mechanisms of HBV entry and the role of NTCP in this process.",2014 Feb 19,"['Watashi, Koichi', 'Urban, Stephan', 'Li, Wenhui', 'Wakita, Takaji']",Int J Mol Sci,,,True
108ebac20ee26fd05a2ba7ad43523957c34d871e,PMC,How Change of Public Transportation Usage Reveals Fear of the SARS Virus in a City,http://dx.doi.org/10.1371/journal.pone.0089405,PMC3960095,24647278,CC BY,"The outbreaks of the severe acute respiratory syndrome (SARS) epidemic in 2003 resulted in unprecedented impacts on people's daily life. One of the most significant impacts to people is the fear of contacting the SARS virus while engaging daily routine activity. Here we use data from daily underground ridership in Taipei City and daily reported new SARS cases in Taiwan to model the dynamics of the public fear of the SARS virus during the wax and wane of the SARS period. We found that for each reported new SARS case there is an immediate loss of about 1200 underground ridership (the fresh fear). These daily loss rates dissipate to the following days with an e-folding time of about 28 days, reflecting the public perception on the risk of contacting SARS virus when traveling with the underground system (the residual fear). About 50% of daily ridership was lost during the peak of the 2003 SARS period, compared with the loss of 80% daily ridership during the closure of the underground system after Typhoon Nari, the loss of 50–70% ridership due to the closure of the governmental offices and schools during typhoon periods, and the loss of 60% daily ridership during Chinese New Year holidays.",2014 Mar 19,"Wang, Kuo-Ying",PLoS One,,,True
638c36249e56a71ae71edd5391b1ca7fafd82daf,PMC,Contrasting Patterns in Mammal–Bacteria Coevolution: Bartonella and Leptospira in Bats and Rodents,http://dx.doi.org/10.1371/journal.pntd.0002738,PMC3961187,24651646,CC BY,"BACKGROUND: Emerging bacterial zoonoses in bats and rodents remain relatively understudied. We conduct the first comparative host–pathogen coevolutionary analyses of bacterial pathogens in these hosts, using Bartonella spp. and Leptospira spp. as a model. METHODOLOGY/PRINCIPAL FINDINGS: We used published genetic data for 51 Bartonella genotypes from 24 bat species, 129 Bartonella from 38 rodents, and 26 Leptospira from 20 bats. We generated maximum likelihood and Bayesian phylogenies for hosts and bacteria, and tested for coevoutionary congruence using programs ParaFit, PACO, and Jane. Bartonella spp. and their bat hosts had a significant coevolutionary fit (ParaFitGlobal = 1.9703, P≤0.001; m(2) global value = 7.3320, P≤0.0001). Bartonella spp. and rodent hosts also indicated strong overall patterns of cospeciation (ParaFitGlobal = 102.4409, P≤0.001; m(2) global value = 86.532, P≤0.0001). In contrast, we were unable to reject independence of speciation events in Leptospira and bats (ParaFitGlobal = 0.0042, P = 0.84; m(2) global value = 4.6310, P = 0.5629). Separate analyses of New World and Old World data subsets yielded results congruent with analysis from entire datasets. We also conducted event-based cophylogeny analyses to reconstruct likely evolutionary histories for each group of pathogens and hosts. Leptospira and bats had the greatest number of host switches per parasite (0.731), while Bartonella and rodents had the fewest (0.264). CONCLUSIONS/SIGNIFICANCE: In both bat and rodent hosts, Bartonella exhibits significant coevolution with minimal host switching, while Leptospira in bats lacks evolutionary congruence with its host and has high number of host switches. Reasons underlying these variable coevolutionary patterns in host range are likely due to differences in disease-specific transmission and host ecology. Understanding the coevolutionary patterns and frequency of host-switching events between bacterial pathogens and their hosts will allow better prediction of spillover between mammal reservoirs, and ultimately to humans.",2014 Mar 20,"['Lei, Bonnie R.', 'Olival, Kevin J.']",PLoS Negl Trop Dis,,,True
dacb58b5ac7adedfeb44dde5632c503c5d37548f,PMC,De novo Fatty Acid Biosynthesis Contributes Significantly to Establishment of a Bioenergetically Favorable Environment for Vaccinia Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1004021,PMC3961357,24651651,CC BY,"The poxvirus life cycle, although physically autonomous from the host nucleus, is nevertheless dependent upon cellular functions. A requirement for de novo fatty acid biosynthesis was implied by our previous demonstration that cerulenin, a fatty acid synthase inhibitor, impaired vaccinia virus production. Here we show that additional inhibitors of this pathway, TOFA and C75, reduce viral yield significantly, with partial rescue provided by exogenous palmitate, the pathway's end-product. Palmitate's major role during infection is not for phospholipid synthesis or protein palmitoylation. Instead, the mitochondrial import and β-oxidation of palmitate are essential, as shown by the impact of etomoxir and trimetazidine, which target these two processes respectively. Moreover, the impact of these inhibitors is exacerbated in the absence of exogenous glucose, which is otherwise dispensable for infection. In contrast to glucose, glutamine is essential for productive viral infection, providing intermediates that sustain the TCA cycle (anaplerosis). Cumulatively, these data suggest that productive infection requires the mitochondrial β-oxidation of palmitate which drives the TCA cycle and energy production. Additionally, infection causes a significant rise in the cellular oxygen consumption rate (ATP synthesis) that is ablated by etomoxir. The biochemical progression of the vaccinia life cycle is not impaired in the presence of TOFA, C75, or etomoxir, although the levels of viral DNA and proteins synthesized are somewhat diminished. However, by reversibly arresting infections at the onset of morphogenesis, and then monitoring virus production after release of the block, we determined that virion assembly is highly sensitive to TOFA and C75. Electron microscopic analysis of cells released into C75 revealed fragmented aggregates of viroplasm which failed to be enclosed by developing virion membranes. Taken together, these data indicate that vaccinia infection, and in particular virion assembly, relies on the synthesis and mitochondrial import of fatty acids, where their β-oxidation drives robust ATP production.",2014 Mar 20,"['Greseth, Matthew D.', 'Traktman, Paula']",PLoS Pathog,,,True
740523d9e53ac786c0a45c790320c219cd0031a4,PMC,MAVS-MKK7-JNK2 Defines a Novel Apoptotic Signaling Pathway during Viral Infection,http://dx.doi.org/10.1371/journal.ppat.1004020,PMC3961361,24651600,CC BY,"Viral infection induces innate immunity and apoptosis. Apoptosis is an effective means to sacrifice virus-infected host cells and therefore restrict the spread of pathogens. However, the underlying mechanisms of this process are still poorly understood. Here, we show that the mitochondrial antiviral signaling protein (MAVS/VISA/Cardif/IPS-1) is critical for SeV (Sendai virus)-induced apoptosis. MAVS specifically activates c-Jun N-terminal kinase 2 (JNK2) but not other MAP kinases. Jnk2−/− cells, but not Jnk1−/− cells, are unable to initiate virus-induced apoptosis and SeV further fails to trigger apoptosis in MAPK kinase 7 (MKK7) knockout (Mkk7−/−) cells. Mechanistically, MAVS recruits MKK7 onto mitochondria via its 3D domain, which subsequently phosphorylates JNK2 and thus activates the apoptosis pathway. Consistently, Jnk2−/− mice, but not Jnk1−/− mice, display marked inflammatory injury in lung and liver after viral challenge. Collectively, we have identified a novel signaling pathway, involving MAVS-MKK7-JNK2, which mediates virus-induced apoptosis and highlights the indispensable role of mitochondrial outer membrane in host defenses.",2014 Mar 20,"['Huang, Yuefeng', 'Liu, Heng', 'Li, Senlin', 'Tang, Yijun', 'Wei, Bo', 'Yu, Huansha', 'Wang, Chen']",PLoS Pathog,,,True
9027b4d1324273bed34f667f3d61d2536e9fd316,PMC,"Concurrent Measurement of Dynamic Changes in Viral Load, Serum Enzymes, T Cell Subsets, and Cytokines in Patients with Severe Fever with Thrombocytopenia Syndrome",http://dx.doi.org/10.1371/journal.pone.0091679,PMC3962368,24658451,CC BY,"Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infection caused by a novel Bunyavirus. Analysis on the dynamic changes of clinical, laboratory, and immunological abnormalities associated with SFTS in a concurrent study is lacking. Thirty-three SFTS patients were admitted to Jiangsu People's Hospital, Nanjing, China, and diagnosis was made based on the clinical symptoms and positive viral RNA detected by RT-PCR. Four patients deceased and twenty-nine survived. Blood samples were collected every other day between Day 5 and Day 15 from the onset of fever. Samples from healthy volunteers were used as normal controls. Peak viral RNA load, serum enzymes, IL-6, and IL-10 were significantly higher in deceased patients compared to survivors. Viral load, serum enzymes, and cytokines declined in survivors within 2 weeks from onset of fever. CD69+ T cells were elevated early after infection while HLA-DR+ and CTLA4+ T cells were elevated during the recovery phase of those who survived. High level SFTSV viral load was concurrently observed with reduced PLT, elevated serum enzymes, elevated pro-inflammatory and anti-inflammatory cytokines, and activation of CD69+ T cells. The degree and pattern of changes in these parameters may indicate the clinical outcome in SFTSV-infected patients.",2014 Mar 21,"['Li, Jun', 'Han, Yaping', 'Xing, Yiping', 'Li, Shuang', 'Kong, Lianhua', 'Zhang, Yongxiang', 'Zhang, Lili', 'Liu, Ning', 'Wang, Qian', 'Wang, Shixia', 'Lu, Shan', 'Huang, Zuhu']",PLoS One,,,True
3db3a962e710f4712e14a5162a9e7f3f136696f6,PMC,Multi-Organ Lesions in Suckling Mice Infected with SARS-Associated Mammalian Reovirus Linked with Apoptosis Induced by Viral Proteins μ1 and σ1,http://dx.doi.org/10.1371/journal.pone.0092678,PMC3963933,24664247,CC BY,"We reported the isolation and characterization of a novel mammalian reassortant reovirus BYD1 that may have played an accomplice role with SARS-coronavirus during the 2003 SARS pandemic. The pathogenic mechanism of this novel reovirus is unknown. Reovirus pathogenicity has been associated with virus-induced apoptosis in cultured cells and in vivo. The reovirus outer capsid protein μ1 is recognized as the primary determinant of reovirus-induced apoptosis. Here, we investigated the apoptosis induced by BYD1, its outer capsid protein μ1, and its cell-attachment protein σ1 to understand the pathogenesis of BYD1. We also investigated BYD1 caused systemic complications in suckling mice. Under electron microscopy, BYD1-infected cells showed characteristics typical of apoptosis. Notably, ectopically expressed μ1 and σ1 induced similar pathological apoptosis, independent of BYD1 infection, in host cells in which they were expressed, which suggests that μ1 and σ1 are both apoptotic virulence factors. Consistent with previous reports of reovirus pathogenicity, suckling mice intracranially inoculated with BYD1 developed central nerve damage, myocarditis, and pneumonia. Collectively, our data suggest that BYD1 μ1- and σ1-induced apoptosis is involved in the multi-organ lesions in a suckling mouse BYD1 infection model.",2014 Mar 24,"['Song, Lihua', 'Lu, Yongfeng', 'He, Jun', 'Yu, Yonghui', 'Zuo, Tingting', 'Li, Yanwei', 'Zhu, Hong', 'Duan, Qing']",PLoS One,,,True
a135f7028fe8bfd36c791323bf28623c06c7b7fb,PMC,AVPdb: a database of experimentally validated antiviral peptides targeting medically important viruses,http://dx.doi.org/10.1093/nar/gkt1191,PMC3964995,24285301,CC BY,"Antiviral peptides (AVPs) have exhibited huge potential in inhibiting viruses by targeting various stages of their life cycle. Therefore, we have developed AVPdb, available online at http://crdd.osdd.net/servers/avpdb, to provide a dedicated resource of experimentally verified AVPs targeting over 60 medically important viruses including Influenza, HCV, HSV, RSV, HBV, DENV, SARS, etc. However, we have separately provided HIV inhibiting peptides in ‘HIPdb’. AVPdb contains detailed information of 2683 peptides, including 624 modified peptides experimentally tested for antiviral activity. In modified peptides a chemical moiety is attached for increasing their efficacy and stability. Detailed information include: peptide sequence, length, source, virus targeted, virus family, cell line used, efficacy (qualitative/quantitative), target step/protein, assay used in determining the efficacy and PubMed reference. The database also furnishes physicochemical properties and predicted structure for each peptide. We have provided user-friendly browsing and search facility along with other analysis tools to help the users. Entering of many synthetic peptide-based drugs in various stages of clinical trials reiterate the importance for the AVP resources. AVPdb is anticipated to cater to the needs of scientific community working for the development of antiviral therapeutics.",2014 Jan 1,"['Qureshi, Abid', 'Thakur, Nishant', 'Tandon, Himani', 'Kumar, Manoj']",Nucleic Acids Res,,,True
2d2d787fd72d87b38275e4deb4b160ad8c80338c,PMC,Proteomics Analysis of the DF-1 Chicken Fibroblasts Infected with Avian Reovirus Strain S1133,http://dx.doi.org/10.1371/journal.pone.0092154,PMC3965424,24667214,CC BY,"BACKGROUND: Avian reovirus (ARV) is a member of the Orthoreovirus genus in the Reoviridae family. It is the etiological agent of several diseases, among which viral arthritis and malabsorption syndrome are the most commercially important, causing considerable economic losses in the poultry industry. Although a small but increasing number of reports have characterized some aspects of ARV infection, global changes in protein expression in ARV-infected host cells have not been examined. The current study used a proteomics approach to obtain a comprehensive view of changes in protein levels in host cells upon infection by ARV. METHODOLOGY AND PRINCIPAL FINDINGS: The proteomics profiles of DF-1 chicken fibroblast cells infected with ARV strain S1133 were analyzed by two-dimensional differential-image gel electrophoresis. The majority of protein expression changes (≥1.5 fold, p<0.05) occurred at 72 h post-infection. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry identified 51 proteins with differential expression levels, including 25 that were upregulated during ARV infection and 26 that were downregulated. These proteins were divided into eight groups according to biological function: signal transduction, stress response, RNA processing, the ubiquitin-proteasome pathway, lipid metabolism, carbohydrate metabolism, energy metabolism, and cytoskeleton organization. They were further examined by immunoblotting to validate the observed alterations in protein expression. CONCLUSION/SIGNIFICANCE: This is the first report of a time-course proteomic analysis of ARV-infected host cells. Notably, all identified proteins involved in signal transduction, RNA processing, and the ubiquitin-proteasome pathway were downregulated in infected cells, whereas proteins involved in DNA synthesis, apoptosis, and energy production pathways were upregulated. In addition, other differentially expressed proteins were linked with the cytoskeleton, metabolism, redox regulation, and stress response. These proteomics data provide valuable information about host cell responses to ARV infection and will facilitate further studies of the molecular mechanisms underlying ARV pathogenesis.",2014 Mar 25,"['Chen, Wen-Ting', 'Wu, Yi-Le', 'Chen, Ting', 'Cheng, Chao-Sheng', 'Chan, Hong-Lin', 'Chou, Hsiu-Chuan', 'Chen, Yi-Wen', 'Yin, Hsien-Sheng']",PLoS One,,,True
2ab24bbc71562ee67437db9fee7f83edb40f4de9,PMC,Imported Case of Acute Respiratory Tract Infection Associated with a Member of Species Nelson Bay Orthoreovirus,http://dx.doi.org/10.1371/journal.pone.0092777,PMC3965453,24667794,CC BY,"A Japanese man suffered from acute respiratory tract infection after returning to Japan from Bali, Indonesia in 2007. Miyazaki-Bali/2007, a strain of the species of Nelson Bay orthoreovirus, was isolated from the patient's throat swab using Vero cells, in which syncytium formation was observed. This is the sixth report describing a patient with respiratory tract infection caused by an orthoreovirus classified to the species of Nelson Bay orthoreovirus. Given the possibility that all of the patients were infected in Malaysia and Indonesia, prospective surveillance on orthoreovirus infections should be carried out in Southeast Asia. Furthermore, contact surveillance study suggests that the risk of human-to-human infection of the species of Nelson Bay orthoreovirus would seem to be low.",2014 Mar 25,"['Yamanaka, Atsushi', 'Iwakiri, Akira', 'Yoshikawa, Tomoki', 'Sakai, Kouji', 'Singh, Harpal', 'Himeji, Daisuke', 'Kikuchi, Ikuo', 'Ueda, Akira', 'Yamamoto, Seigo', 'Miura, Miho', 'Shioyama, Yoko', 'Kawano, Kimiko', 'Nagaishi, Tokiko', 'Saito, Minako', 'Minomo, Masumi', 'Iwamoto, Naoyasu', 'Hidaka, Yoshio', 'Sohma, Hirotoshi', 'Kobayashi, Takeshi', 'Kanai, Yuta', 'Kawagishi, Takehiro', 'Nagata, Noriyo', 'Fukushi, Shuetsu', 'Mizutani, Tetsuya', 'Tani, Hideki', 'Taniguchi, Satoshi', 'Fukuma, Aiko', 'Shimojima, Masayuki', 'Kurane, Ichiro', 'Kageyama, Tsutomu', 'Odagiri, Takato', 'Saijo, Masayuki', 'Morikawa, Shigeru']",PLoS One,,,True
e172d0ebcbb5e8488f19e2193ac9a9ed96f60efb,PMC,Commentary on the Regulation of Viral Proteins in Autophagy Process,http://dx.doi.org/10.1155/2014/962915,PMC3966343,24734254,CC BY,"The ability to subvert intracellular antiviral defenses is necessary for virus to survive as its replication occurs only in the host cells. Viruses have to modulate cellular processes and antiviral mechanisms to their own advantage during the entire virus life cycle. Autophagy plays important roles in cell regulation. Its function is not only to catabolize aggregate proteins and damaged organelles for recycling but also to serve as innate immunity to remove intracellular pathogenic elements such as viruses. Nevertheless, some viruses have evolved to negatively regulate autophagy by inhibiting its formation. Even more, some viruses have employed autophagy to benefit their replication. To date, there are more and more growing evidences uncovering the functions of many viral proteins to regulate autophagy through different cellular pathways. In this review, we will discuss the relationship between viruses and autophagy and summarize the current knowledge on the functions of viral proteins contributing to affect autophagy process.",2014 Mar 10,"['Cheng, Ching-Yuan', 'Chi, Pei-I', 'Liu, Hung-Jen']",Biomed Res Int,,,True
29ada2d0f89dbeee105c3f95b7df0ab204d9a444,PMC,"A New Species of Mesonivirus from the Northern Territory, Australia",http://dx.doi.org/10.1371/journal.pone.0091103,PMC3966781,24670468,CC BY,"Here we describe Casuarina virus (CASV), a new virus in the family Mesoniviridae. This is the first report of a mesonivirus in Australia, which extends the geographical range of this virus family to 3 continents. The virus was isolated in 2010 from Coquillettidia xanthogaster mosquitoes during surveillance in the suburbs of Darwin, the capital of the Northern Territory. Cryo-electron microscopy of the CASV virions revealed spherical particles of 65 nm in size with large club-shaped projections of approximately 15 nm in length. The new virus was most closely related to Alphamesonivirus 1, the only currently recognized species in the family. In 2013 a further 5 putative new mesonivirus species were described: Hana, Méno, Nsé, Moumo and Dak Nong viruses. The evolutionary distance between CASV and two of its closest relatives, Cavally and Hana viruses (Jones-Taylor-Thornton distance of 0.151 and 0.224, respectively), along with its isolation from a different genus of mosquitoes captured on a separate continent indicate that CASV is a new species.",2014 Mar 26,"['Warrilow, David', 'Watterson, Daniel', 'Hall, Roy A.', 'Davis, Steven S.', 'Weir, Richard', 'Kurucz, Nina', 'Whelan, Peter', 'Allcock, Richard', 'Hall-Mendelin, Sonja', 'O’Brien, Caitlin A.', 'Hobson-Peters, Jody']",PLoS One,,,True
9dbde5d85011e2cb16e7d996421db75323ea21c0,PMC,Molecular Characterization of Major Structural Protein Genes of Avian Coronavirus Infectious Bronchitis Virus Isolates in Southern China,http://dx.doi.org/10.3390/v5123007,PMC3967158,24304696,CC BY,"To gain comprehensive genetic information of circulating avian coronavirus infectious bronchitis virus (IBV) isolates in China, analysis of the phylogenetic tree, entropy of the amino acid sequences, and the positive selection as well as computational recombinations of S1, M and N genes of 23 IBV isolates was conducted in the present study. The phylogenetic trees based on the S1, M and N genes exhibited considerably different topology and the CK/CH/LSC/99I-type isolates were the predominant IBVs based on the phylogenetic analysis of S1 gene. Results of entropy of amino acid sequences revealed that the S1 gene had the largest variation; the M gene had less variation than the N gene. Positive selections were detected in not only S1 but also M and N gene proteins. In addition, five S1 gene recombinants between vaccine strain 4/91 and CK/CH/LSC/99I-type field isolate were confirmed. In conclusion, multiple IBV genotypes co-circulated; genetic diversity and positive selections existed in S1, M and N genes; 4/91 vaccine recombinants emerged in China. Our results show that field IBVs in China are continuing to evolve and vaccine strains may have an important role in the appearance of new IBV strains via recombination. In addition, the present study indicates that IBV evolution is driven by both generations of genetic diversity and selection.",2013 Dec 4,"['Mo, Mei-Lan', 'Li, Meng', 'Huang, Bai-Cheng', 'Fan, Wen-Sheng', 'Wei, Ping', 'Wei, Tian-Chao', 'Cheng, Qiu-Ying', 'Wei, Zheng-Ji', 'Lang, Ya-Hui']",Viruses,,,True
dcc4db04a2a7001e0b9931be5648c7f0cc233620,PMC,Make Yourself at Home: Viral Hijacking of the PI3K/Akt Signaling Pathway,http://dx.doi.org/10.3390/v5123192,PMC3967167,24351799,CC BY,"As viruses do not possess genes encoding for proteins required for translation, energy metabolism or membrane biosynthesis, they are classified as obligatory intracellular parasites that depend on a host cell to replicate. This genome limitation forces them to gain control over cellular processes to ensure their successful propagation. A diverse spectrum of virally encoded proteins tackling a broad spectrum of cellular pathways during most steps of the viral life cycle ranging from the host cell entry to viral protein translation has evolved. Since the host cell PI3K/Akt signaling pathway plays a critical regulatory role in many cellular processes including RNA processing, translation, autophagy and apoptosis, many viruses, in widely varying ways, target it. This review focuses on a number of remarkable examples of viral strategies, which exploit the PI3K/Akt signaling pathway for effective viral replication.",2013 Dec 16,"['Diehl, Nora', 'Schaal, Heiner']",Viruses,,,True
f1f24521928f5d8565a15a17bd7f79239a3d4116,PMC,A Schiff Base-Derived Copper (II) Complex Is a Potent Inducer of Apoptosis in Colon Cancer Cells by Activating the Intrinsic Pathway,http://dx.doi.org/10.1155/2014/540463,PMC3967396,24737979,CC BY,"Metal-based drugs with extensive clinical applications hold great promise for the development of cancer chemotherapeutic agents. In the last few decades, Schiff bases and their complexes have become well known for their extensive biological potential. In the present study, we examined the antiproliferative effect of a copper (II) complex on HT-29 colon cancer cells. The Cu(BrHAP)(2 ) Schiff base compound demonstrated a potent antiproliferative effect in HT-29 cells, with an IC(50 )value of 2.87 μg/ml after 72 h of treatment. HT-29 cells treated with Cu (II) complexes underwent apoptosis death, as exhibited by a progressive elevation in the proportion of the G(1 ) cell population. At a concentration of 6.25 μg/ml, the Cu(BrHAP)(2 ) compound caused significant elevation in ROS production following perturbation of mitochondrial membrane potential and cytochrome c release, as assessed by the measurement of fluorescence intensity in stained cells. Furthermore, the activation of caspases 3/7 and 9 was part of the Cu (II) complex-induced apoptosis, which confirmed the involvement of mitochondrial-mediated apoptosis. Meanwhile, there was no significant activation of caspase-8. Taken together, these results imply that the Cu(BrHAP)(2 ) compound is a potential candidate for further in vivo and clinical colon cancer studies to develop novel chemotherapeutic agents derived from metal-based agents.",2014 Mar 5,"['Hajrezaie, Maryam', 'Paydar, Mohammadjavad', 'Zorofchian Moghadamtousi, Soheil', 'Hassandarvish, Pouya', 'Gwaram, Nura Suleiman', 'Zahedifard, Maryam', 'Rouhollahi, Elham', 'Karimian, Hamed', 'Looi, Chung Yeng', 'Ali, Hapipah Mohd', 'Abdul Majid, Nazia', 'Abdulla, Mahmood Ameen']",ScientificWorldJournal,,,True
c4aa9bb066a64db00b8bdd44d5c021c5603a09a2,PMC,"Comparison of Patients Hospitalized With Influenza A Subtypes H7N9, H5N1, and 2009 Pandemic H1N1",http://dx.doi.org/10.1093/cid/ciu053,PMC3967826,24488975,CC BY,"Background. Influenza A(H7N9) viruses isolated from humans show features suggesting partial adaptation to mammals. To provide insights into the pathogenesis of H7N9 virus infection, we compared risk factors, clinical presentation, and progression of patients hospitalized with H7N9, H5N1, and 2009 pandemic H1N1 (pH1N1) virus infections. Methods. We compared individual-level data from patients hospitalized with infection by H7N9 (n = 123), H5N1 (n = 119; 43 China, 76 Vietnam), and pH1N1 (n = 3486) viruses. We assessed risk factors for hospitalization after adjustment for age- and sex-specific prevalence of risk factors in the general Chinese population. Results. The median age of patients with H7N9 virus infection was older than other patient groups (63 years; P < .001) and a higher proportion was male (71%; P < .02). After adjustment for age and sex, chronic heart disease was associated with an increased risk of hospitalization with H7N9 (relative risk, 9.68; 95% confidence interval, 5.24–17.9). H7N9 patients had similar patterns of leukopenia, thrombocytopenia, and elevated alanine aminotransferase, creatinine kinase, C-reactive protein, and lactate dehydrogenase to those seen in H5N1 patients, which were all significantly different from pH1N1 patients (P < .005). H7N9 patients had a longer duration of hospitalization than either H5N1 or pH1N1 patients (P < .001), and the median time from onset to death was 18 days for H7N9 (P = .002) vs 11 days for H5N1 and 15 days for pH1N1 (P = .154). Conclusions. The identification of known risk factors for severe seasonal influenza and the more protracted clinical course compared with that of H5N1 suggests that host factors are an important contributor to H7N9 severity.",2014 Apr 15,"['Wang, Chen', 'Yu, Hongjie', 'Horby, Peter W.', 'Cao, Bin', 'Wu, Peng', 'Yang, Shigui', 'Gao, Hainv', 'Li, Hui', 'Tsang, Tim K.', 'Liao, Qiaohong', 'Gao, Zhancheng', 'Ip, Dennis K. M.', 'Jia, Hongyu', 'Jiang, Hui', 'Liu, Bo', 'Ni, Michael Y.', 'Dai, Xiahong', 'Liu, Fengfeng', 'Van Kinh, Nguyen', 'Liem, Nguyen Thanh', 'Hien, Tran Tinh', 'Li, Yu', 'Yang, Juan', 'Wu, Joseph T.', 'Zheng, Yaming', 'Leung, Gabriel M.', 'Farrar, Jeremy J.', 'Cowling, Benjamin J.', 'Uyeki, Timothy M.', 'Li, Lanjuan']",Clin Infect Dis,,,True
56ac442721c9e0f335024cb4e414c9f00bc53aea,PMC,Viral OTU Deubiquitinases: A Structural and Functional Comparison,http://dx.doi.org/10.1371/journal.ppat.1003894,PMC3968130,24676359,CC BY,"Recent studies have revealed that proteases encoded by three very diverse RNA virus groups share structural similarity with enzymes of the Ovarian Tumor (OTU) superfamily of deubiquitinases (DUBs). The publication of the latest of these reports in quick succession prevented proper recognition and discussion of the shared features of these viral enzymes. Here we provide a brief structural and functional comparison of these virus-encoded OTU DUBs. Interestingly, although their shared structural features and substrate specificity tentatively place them within the same protease superfamily, they also show interesting differences that trigger speculation as to their origins.",2014 Mar 27,"['Bailey-Elkin, Ben A.', 'van Kasteren, Puck B.', 'Snijder, Eric J.', 'Kikkert, Marjolein', 'Mark, Brian L.']",PLoS Pathog,,,True
2a5d09bdb532096261be55490d99eb996e05ea18,PMC,Influenza-Like Illnesses in Senegal: Not Only Focus on Influenza Viruses,http://dx.doi.org/10.1371/journal.pone.0093227,PMC3968133,24675982,CC BY,"Influenza surveillance in African countries was initially restricted to the identification of circulating strains. In Senegal, the network has recently been enhanced (i) to include epidemiological data from Dakar and other regions and (ii) to extend virological surveillance to other respiratory viruses. Epidemiological data from the sentinel sites is transmitted daily by mobile phone. The data include those for other febrile syndromes similar to influenza-like illnesses (ILI), corresponding to integrated approach. Also, clinical samples are randomly selected and analyzed for influenza and other respiratory viruses. There were 101,640 declared visits to the 11 sentinel sites between week 11-2012 and week 35-2013; 22% of the visits were for fever syndromes and 23% of the cases of fever syndrome were ILI. Influenza viruses were the second most frequent cause of ILI (20%), after adenoviruses (21%) and before rhinoviruses (18%) and enteroviruses (15%). Co-circulation and co-infection were frequent and were responsible for ILI peaks. The first months of implementation of the enhanced surveillance system confirmed that viruses other the influenza make large contributions to influenza-like illnesses. It is therefore important to consider these etiologies in the development of strategies to reduce respiratory infections. More informative tools and research studies are required to assess the burden of respiratory infections in developing countries.",2014 Mar 27,"['Dia, Ndongo', 'Diene Sarr, Fatoumata', 'Thiam, Diamilatou', 'Faye Sarr, Tening', 'Espié, Emmanuelle', 'OmarBa, Ibrahim', 'Coly, Malang', 'Niang, Mbayame', 'Richard, Vincent', None]",PLoS One,,,True
d5325b37145bcf18e4b7bf64b7c93ceef20273b5,PMC,Orsay virus utilizes ribosomal frameshifting to express a novel protein that is incorporated into virions(),http://dx.doi.org/10.1016/j.virol.2013.12.016,PMC3969245,24503084,CC BY,"Orsay virus is the first identified virus that is capable of naturally infecting Caenorhabditis elegans. Although it is most closely related to nodaviruses, Orsay virus differs from nodaviruses in its genome organization. In particular, the Orsay virus RNA2 segment encodes a putative novel protein of unknown function, termed delta, which is absent from all known nodaviruses. Here we present evidence that Orsay virus utilizes a ribosomal frameshifting strategy to express a novel fusion protein from the viral capsid (alpha) and delta ORFs. Moreover, the fusion protein was detected in purified virus fractions, demonstrating that it is most likely incorporated into Orsay virions. Furthermore, N-terminal sequencing of both the fusion protein and the capsid protein demonstrated that these proteins must be translated from a non-canonical initiation site. While the function of the alpha–delta fusion remains cryptic, these studies provide novel insights into the fundamental properties of this new clade of viruses.",2014 Feb,"['Jiang, Hongbing', 'Franz, Carl J.', 'Wu, Guang', 'Renshaw, Hilary', 'Zhao, Guoyan', 'Firth, Andrew E.', 'Wang, David']",Virology,,,False
d3d998de1e3cb950c425decbadc73af2c26102fb,PMC,More Novel Hantaviruses and Diversifying Reservoir Hosts — Time for Development of Reservoir-Derived Cell Culture Models?,http://dx.doi.org/10.3390/v6030951,PMC3970132,24576845,CC BY,"Due to novel, improved and high-throughput detection methods, there is a plethora of newly identified viruses within the genus Hantavirus. Furthermore, reservoir host species are increasingly recognized besides representatives of the order Rodentia, now including members of the mammalian orders Soricomorpha/Eulipotyphla and Chiroptera. Despite the great interest created by emerging zoonotic viruses, there is still a gross lack of in vitro models, which reflect the exclusive host adaptation of most zoonotic viruses. The usually narrow host range and genetic diversity of hantaviruses make them an exciting candidate for studying virus-host interactions on a cellular level. To do so, well-characterized reservoir cell lines covering a wide range of bat, insectivore and rodent species are essential. Most currently available cell culture models display a heterologous virus-host relationship and are therefore only of limited value. Here, we review the recently established approaches to generate reservoir-derived cell culture models for the in vitro study of virus-host interactions. These successfully used model systems almost exclusively originate from bats and bat-borne viruses other than hantaviruses. Therefore we propose a parallel approach for research on rodent- and insectivore-borne hantaviruses, taking the generation of novel rodent and insectivore cell lines from wildlife species into account. These cell lines would be also valuable for studies on further rodent-borne viruses, such as orthopox- and arenaviruses.",2014 Feb 26,"['Eckerle, Isabella', 'Lenk, Matthias', 'Ulrich, Rainer G.']",Viruses,,,True
1d0c8b03f2da34c55161d6205a97d06d373762c0,PMC,Isolation and Identification of Feline Herpesvirus Type 1 from a South China Tiger in China,http://dx.doi.org/10.3390/v6031004,PMC3970135,24590411,CC BY,"In 2012, an FHV-1-like virus was isolated from a tiger that presented with clinical signs of sialorrhea, sneezing and purulent rhinorrhea. Isolation was performed with the FK81 cell line, and the virus was identified by PCR, transmission electron microscopy (TEM), and the phylogenetic analysis of the partial thymidine kinase (TK) and glycoprotein B (gB) genes. A total of 253 bp of the TK gene and 566 bp of the gB gene were amplified from the trachea of the tiger by PCR/RT-PCR method. Phylogenetic analysis showed that the isolate belonged to the same cluster with other FHV-1 strains obtained from GenBank. Herpes-like viruses with an envelope and diameters of approximately 200 nm were observed in the culture supernatants of FK81 cells inoculated with samples from the tiger. The FHV-1 infection was confirmed by an animal challenge experiment in a cat model. Our finding extends the host range of FHV-1 and has implications for FHV-1 infection and South China tiger conservation.",2014 Feb 28,"['Sun, Heting', 'Li, Yuanguo', 'Jiao, Weiyi', 'Liu, Cunfa', 'Liu, Xiujuan', 'Wang, Haijun', 'Hua, Fuyou', 'Dong, Jianxiu', 'Fan, Shengtao', 'Yu, Zhijun', 'Gao, Yuwei', 'Xia, Xianzhu']",Viruses,,,True
1c956bc94ce590a7ca6c2ace2c0766bbbbfaa0e3,PMC,Development of Lectin-Linked Immunomagnetic Separation for the Detection of Hepatitis A Virus,http://dx.doi.org/10.3390/v6031037,PMC3970137,24599279,CC BY,"The accuracy and sensitivity of PCR-based methods for detection of hepatitis A virus (HAV) are dependent on the methods used to separate and concentrate the HAV from the infected cells. The pH and ionic strength affect the binding affinity of the virus to cells. In this study, we initially investigated the effects of pH (4.0–10.0) and metal ions (Fe(2+), Co(2+), Cu(2+), Mg(2+), K(+), and Ca(2+)) on the binding of HAV to oyster digestive cells. The lowest relative binding (RB) of HAV to the cells was found at pH 4.0 and in FeSO(4) solution (64.6% and 68.1%, respectively). To develop an alternative to antibody-dependent immunomagnetic separation prior to detection of HAV using RT-PCR, the binding of HAV to five lectins, peanut agglutinin (PNA), Dolichos biflorus agglutinin (DBA), Helix pomatia agglutinin (HPA), Ulex europaeus agglutinin (UEA-1) and soybean agglutinin (SBA), was evaluated using ELISAs. SBA showed significantly higher RB to HAV than the other lectins tested. In addition, HAV could be concentrated within 30 min using SBA-linked magnetic bead separation (SMS) prior to the RT-PCR assay. Our findings demonstrate the feasibility of using SMS combined with RT-PCR to detect HAV at dilutions ranging from 10(−1)–10(−4) of a HAV stock (titer: 10(4) TCID(50)/mL).",2014 Mar 4,"['Ko, Sang-Mu', 'Kwon, Joseph', 'Vaidya, Bipin', 'Choi, Jong Soon', 'Lee, Hee-Min', 'Oh, Myung-Joo', 'Bae, Hyeun-Jong', 'Cho, Se-Young', 'Oh, Kyung-Seo', 'Kim, Duwoon']",Viruses,,,True
507796937879c600ac886d0aa7080e73bedb5044,PMC,Molecular Characterizations of Subcellular Localization Signals in the Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.3390/v6031253,PMC3970149,24632575,CC BY,"The nucleolus is a dynamic subnuclear structure, which is crucial to the normal operation of the eukaryotic cell. The porcine epidemic diarrhea virus (PEDV), coronavirus nucleocapsid (N) protein, plays important roles in the process of virus replication and cellular infection. Virus infection and transfection showed that N protein was predominately localized in the cytoplasm, but also found in the nucleolus in Vero E6 cells. Furthermore, by utilizing fusion proteins with green fluorescent protein (GFP), deletion mutations or site-directed mutagenesis of PEDV N protein, coupled with live cell imaging and confocal microscopy, it was revealed that, a region spanning amino acids (aa), 71–90 in region 1 of the N protein was sufficient for nucleolar localization and R87 and R89 were critical for its function. We also identified two nuclear export signals (NES, aa221–236, and 325–364), however, only the nuclear export signal (aa325–364) was found to be functional in the context of the full-length N protein. Finally, the activity of this nuclear export signal (NES) was inhibited by the antibiotic Lepomycin B, suggesting that N is exported by a chromosome region maintenance 1-related export pathway.",2014 Mar 13,"['Shi, Da', 'Lv, Maojie', 'Chen, Jianfei', 'Shi, Hongyan', 'Zhang, Sha', 'Zhang, Xin', 'Feng, Li']",Viruses,,,True
4ff3cd099988eec4079249528fb8db645b3c9490,PMC,Hantavirus Immunology of Rodent Reservoirs: Current Status and Future Directions,http://dx.doi.org/10.3390/v6031317,PMC3970152,24638205,CC BY,"Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a significant contributory role in these diseases. However, in reservoir hosts that have been closely examined, little or no pathology occurs and infection is persistent despite evidence of adaptive immune responses. Because most hantavirus reservoirs are not model organisms, it is difficult to conduct meaningful experiments that might shed light on how the viruses evade sterilizing immune responses and why immunopathology does not occur. Despite these limitations, recent advances in instrumentation and bioinformatics will have a dramatic impact on understanding reservoir host responses to hantaviruses by employing a systems biology approach to identify important pathways that mediate virus/reservoir relationships.",2014 Mar 14,"['Schountz, Tony', 'Prescott, Joseph']",Viruses,,,True
d311746113fa03b25d129db6c7acc6182499d679,PMC,Asthmatics with exacerbation during acute respiratory illness exhibit unique transcriptional signatures within the nasal mucosa,http://dx.doi.org/10.1186/gm520,PMC3971347,24433494,CC BY,"BACKGROUND: Acute respiratory illness is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular events characterizing acute respiratory illness-induced asthma exacerbations, we undertook a transcriptional profiling study of the nasal mucosa over the course of acute respiratory illness amongst individuals with a history of asthma, allergic rhinitis and no underlying respiratory disease. METHODS: Transcriptional profiling experiments were performed using the Agilent Whole Human Genome 4X44K array platform. Time point-based microarray and principal component analyses were conducted to identify and distinguish acute respiratory illness-associated transcriptional profiles over the course of our study. Gene enrichment analysis was conducted to identify biological processes over-represented within each acute respiratory illness-associated profile, and gene expression was subsequently confirmed by quantitative polymerase chain reaction. RESULTS: We found that acute respiratory illness is characterized by dynamic, time-specific transcriptional profiles whose magnitudes of expression are influenced by underlying respiratory disease and the mucosal repair signature evoked during acute respiratory illness. Most strikingly, we report that people with asthma who experience acute respiratory illness-induced exacerbations are characterized by a reduced but prolonged inflammatory immune response, inadequate activation of mucosal repair, and the expression of a newly described exacerbation-specific transcriptional signature. CONCLUSION: Findings from our study represent a significant contribution towards clarifying the complex molecular interactions that typify acute respiratory illness-induced asthma exacerbations.",2014 Jan 17,"['McErlean, Peter', 'Berdnikovs, Sergejs', 'Favoreto, Silvio', 'Shen, Junqing', 'Biyasheva, Assel', 'Barbeau, Rebecca', 'Eisley, Chris', 'Barczak, Andrea', 'Ward, Theresa', 'Schleimer, Robert P', 'Erle, David J', 'Boushey, Homer A', 'Avila, Pedro C']",Genome Med,,,True
2b9a00927657405449eeb367dc660fb109fe017c,PMC,Asthmatics with exacerbation during acute respiratory illness exhibit unique transcriptional signatures within the nasal mucosa,http://dx.doi.org/10.1186/gm520,PMC3971347,24433494,CC BY,"BACKGROUND: Acute respiratory illness is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular events characterizing acute respiratory illness-induced asthma exacerbations, we undertook a transcriptional profiling study of the nasal mucosa over the course of acute respiratory illness amongst individuals with a history of asthma, allergic rhinitis and no underlying respiratory disease. METHODS: Transcriptional profiling experiments were performed using the Agilent Whole Human Genome 4X44K array platform. Time point-based microarray and principal component analyses were conducted to identify and distinguish acute respiratory illness-associated transcriptional profiles over the course of our study. Gene enrichment analysis was conducted to identify biological processes over-represented within each acute respiratory illness-associated profile, and gene expression was subsequently confirmed by quantitative polymerase chain reaction. RESULTS: We found that acute respiratory illness is characterized by dynamic, time-specific transcriptional profiles whose magnitudes of expression are influenced by underlying respiratory disease and the mucosal repair signature evoked during acute respiratory illness. Most strikingly, we report that people with asthma who experience acute respiratory illness-induced exacerbations are characterized by a reduced but prolonged inflammatory immune response, inadequate activation of mucosal repair, and the expression of a newly described exacerbation-specific transcriptional signature. CONCLUSION: Findings from our study represent a significant contribution towards clarifying the complex molecular interactions that typify acute respiratory illness-induced asthma exacerbations.",2014 Jan 17,"['McErlean, Peter', 'Berdnikovs, Sergejs', 'Favoreto, Silvio', 'Shen, Junqing', 'Biyasheva, Assel', 'Barbeau, Rebecca', 'Eisley, Chris', 'Barczak, Andrea', 'Ward, Theresa', 'Schleimer, Robert P', 'Erle, David J', 'Boushey, Homer A', 'Avila, Pedro C']",Genome Med,,,False
8af0901c4f1252ca252a8618a346c88b3b65ae1b,PMC,Potential Geographic Distribution of the Novel Avian-Origin Influenza A (H7N9) Virus,http://dx.doi.org/10.1371/journal.pone.0093390,PMC3972139,24690878,CC BY,"BACKGROUND: In late March 2013, a new avian-origin influenza virus emerged in eastern China. This H7N9 subtype virus has since infected 240 people and killed 60, and has awakened global concern as a potential pandemic threat. Ecological niche modeling has seen increasing applications as a useful tool in mapping geographic potential and risk of disease transmission. METHODOLOGY/PRINCIPALS: We developed two datasets based on seasonal variation in Normalized Difference Vegetation Index (NDVI) from the MODIS sensor to characterize environmental dimensions of H7N9 virus. One-third of well-documented cases was used to test robustness of models calibrated based on the remaining two-thirds, and model significance was tested using partial ROC approaches. A final niche model was calibrated using all records available. CONCLUSIONS/SIGNIFICANCE: Central-eastern China appears to represent an area of high risk for H7N9 spread, but suitable areas were distributed more spottily in the north and only along the coast in the south; highly suitable areas also were identified in western Taiwan. Areas identified as presenting high risk for H7N9 spread tend to present consistent NDVI values through the year, whereas unsuitable areas show greater seasonal variation.",2014 Apr 1,"['Zhu, Gengping', 'Peterson, A. Townsend']",PLoS One,,,True
535c73393b8f68ef2f9081e1e07d0d0aa0d44a8c,PMC,New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) IV: Circulating ACE2 as a Biomarker of Systolic Dysfunction in Human Hypertension and Heart Failure,http://dx.doi.org/10.1371/journal.pone.0087845,PMC3972189,24691269,CC BY,"BACKGROUND: Growing evidence exists for soluble Angiotensin Converting Enzyme-2 (sACE2) as a biomarker in definitive heart failure (HF), but there is little information about changes in sACE2 activity in hypertension with imminent heart failure and in reverse remodeling. METHODS, FINDINGS: Patients with systolic HF (NYHAII-IV, enrolled for cardiac resynchronisation therapy, CRT, n = 100) were compared to hypertensive patients (n = 239) and to a healthy cohort (n = 45) with preserved ejection fraction (EF>50%) in a single center prospective clinical study. The status of the heart failure patients were checked before and after CRT. Biochemical (ACE and sACE2 activity, ACE concentration) and echocardiographic parameters (EF, left ventricular end-diastolic (EDD) and end-systolic diameter (ESD) and dP/dt) were measured. sACE2 activity negatively correlated with EF and positively with ESD and EDD in all patient's populations, while it was independent in the healthy cohort. sACE2 activity was already increased in the hypertensive group, where signs for imminent heart failure (slightly decreased EF and barely increased NT-proBNP levels) were detected. sACE2 activities further increased in patients with definitive heart failure (EF<50%), while sACE2 activities decreased with the improvement of the heart failure after CRT (reverse remodeling). Serum angiotensin converting enzyme (ACE) concentrations were lower in the diseased populations, but did not show a strong correlation with the echocardiographic parameters. CONCLUSIONS: Soluble ACE2 activity appears to be biomarker in heart failure, and in hypertension, where heart failure may be imminent. Our data suggest that sACE2 is involved in the pathomechanism of hypertension and HF.",2014 Apr 1,"['Úri, Katalin', 'Fagyas, Miklós', 'Mányiné Siket, Ivetta', 'Kertész, Attila', 'Csanádi, Zoltán', 'Sándorfi, Gábor', 'Clemens, Marcell', 'Fedor, Roland', 'Papp, Zoltán', 'Édes, István', 'Tóth, Attila', 'Lizanecz, Erzsébet']",PLoS One,,,True
1516a62bffb7478ad5cbec0bde15290baf5384a3,PMC,Apoptotic Response through a High Mobility Box 1 Protein-Dependent Mechanism in LPS/GalN-Induced Mouse Liver Failure and Glycyrrhizin-Mediated Inhibition,http://dx.doi.org/10.1371/journal.pone.0092884,PMC3972228,24690901,CC BY,"HMGB1 is a nuclear component involved in nucleosome stabilization and transcription regulation, but extracellularly it is able to serve as a potential late mediator of lethality. In the present study, we explored inflammation-promoting activity of HMGB1 and blockade of extracellular release of HMGB1 by glycyrrhizin (GL) in LPS/GalN-triggered mouse liver injury. At 1 to 10 h after LPS/GalN-treatment, mice were anesthetized to collect blood from heart puncture, and serum transaminase and HMGB1 were evaluated. Administration of LPS/GalN precipitated tissue injury associated with time-dependent alteration in HMGB1 serum levels. At 8 h nuclear immunoreactive products were remarkably reduced and extracellular HMGB1 expression was found exclusively in the pericentral foci. The treatment with GL significantly down-regulated the serum levels of ALT, AST, and HMGB1 in addition to the strong inhibition of tissue injury and extracellular immunoreactivity to HMGB1 and to acetylated-lysine. Furthermore, GL brought about a significant decrease in the number of apoptotic hepatocytes labeled with TUNEL-method. On the basis of these results, three apoptosis-associated genes were identified with microarray analysis and real-time PCR. The ChIP-assay revealed the binding of HMGB1 protein to Gsto1 promoter sequence in LPS/GalN-treated mice and the remarkable decrease in combined HMGB1 protein by GL. The current findings claim that a single injection of LPS/GalN might stimulate apoptosis of hepatocytes through the binding of HMGB1 protein to Gsto1 promoter region and that GL-treatment might prevent the apoptosis and inflammatory infiltrates caused with LPS/GalN-injection by disturbing the binding of HMGB1 protein to Gsto1 promoter sequence.",2014 Apr 1,"['Kuroda, Noriyuki', 'Inoue, Kouji', 'Ikeda, Tadayuki', 'Hara, Yaiko', 'Wake, Kenjiro', 'Sato, Tetsuji']",PLoS One,,,True
5dc0c03f8620c881a56b6b17db77b6ffe430ca28,PMC,Divergent Roles of Autophagy in Virus Infection,http://dx.doi.org/10.3390/cells2010083,PMC3972664,24709646,CC BY,"Viruses have played an important role in human evolution and have evolved diverse strategies to co-exist with their hosts. As obligate intracellular pathogens, viruses exploit and manipulate different host cell processes, including cellular trafficking, metabolism and immunity-related functions, for their own survival. In this article, we review evidence for how autophagy, a highly conserved cellular degradative pathway, serves either as an antiviral defense mechanism or, alternatively, as a pro-viral process during virus infection. Furthermore, we highlight recent reports concerning the role of selective autophagy in virus infection and how viruses manipulate autophagy to evade lysosomal capture and degradation.",2013 Jan 25,"['Chiramel, Abhilash I.', 'Brady, Nathan R.', 'Bartenschlager, Ralf']",Cells,,,True
de95f39159534068d4a1aef3e5d6a884d1c39656,PMC,"CD8+ T Lymphocyte Epitopes From The Herpes Simplex Virus Type 2 ICP27, VP22 and VP13/14 Proteins To Facilitate Vaccine Design And Characterization",http://dx.doi.org/10.3390/cells2010019,PMC3972665,24709642,CC BY,"CD8+ T cells have the potential to control HSV-2 infection. However, limited information has been available on CD8+ T cell epitopes or the functionality of antigen specific T cells during infection or following immunization with experimental vaccines. Peptide panels from HSV-2 proteins ICP27, VP22 and VP13/14 were selected from in silico predictions of binding to human HLA-A*0201 and mouse H-2Kd, Ld and Dd molecules. Nine previously uncharacterized CD8+ T cell epitopes were identified from HSV-2 infected BALB/c mice. HSV-2 specific peptide sequences stabilized HLA-A*02 surface expression with intermediate or high affinity binding. Peptide specific CD8+ human T cell lines from peripheral blood lymphocytes were generated from a HLA-A*02+ donor. High frequencies of peptide specific CD8+ T cell responses were elicited in mice by DNA vaccination with ICP27, VP22 and VP13/14, as demonstrated by CD107a mobilization. Vaccine driven T cell responses displayed a more focused immune response than those induced by viral infection. Furthermore, vaccination with ICP27 reduced viral shedding and reduced the clinical impact of disease. In conclusion, this study describes novel HSV-2 epitopes eliciting strong CD8+ T cell responses that may facilitate epitope based vaccine design and aid immunomonitoring of antigen specific T cell frequencies in preclinical and clinical settings.",2013 Jan 4,"['Platt, Rebecca J.', 'Khodai, Tansi', 'Townend, Tim J.', 'Bright, Helen H.', 'Cockle, Paul', 'Perez-Tosar, Luis', 'Webster, Rob', 'Champion, Brian', 'Hickling, Timothy P.', 'Mirza, Fareed']",Cells,,,True
8b248d30d63f97ce5c6aa8f1a6c61a8d7f4c914e,PMC,"Prevalence and correlates of influenza-a in piggery workers and pigs in two communities in Lagos, Nigeria",http://dx.doi.org/10.11604/pamj.2013.16.102.1450,PMC3972905,24711881,CC BY,"INTRODUCTION: Worldwide, three Influenza-A virus subtypes (H1N1, H1N2 and H3N2) in swine are major public health issues. In Nigeria, the existence of these subtypes in pigs has not been well studied. This study aimed at determining the prevalence and correlates of Influenza-A viruses circulating in piggery workers and pigs in Oke-aro and Goshen communities in Lagos, Nigeria. METHODS: Nasal swabs were taken from 197 consenting piggery workers and 281 randomly selected pigs to determine the prevalence of Influenza-A (H1, H3, H5) using Reverse Transcriptase Polymerase Chain Reaction test (gene M). An interviewer administered questionnaire was used to collect information on demography, Influenza-A related symptoms experienced, personal hygiene and management practices from the piggery workers. Descriptive statistics was used and chi square test performed at 5% significant level. RESULTS: All piggery workers and pigs’ nasal swabs tested negative for Influenza-A viruses, hence, association could not be tested. Mean age of piggery workers was 41 ± 13.6 years and 60% were females. Forty two percent were farm attendants, 38.0% were pig farmers and the rest butchers. Nineteen percent had history of headache; 14.0% had catarrh and cough; 4.0% had sore-throat; 5.0% had diarrhea; while 48.0% had muscle pain at the time of data collection. The mean body temperature for the pig workers was 36.5 ± 0.5 °C. A significant difference (p<0.05) existed among piggery workers who had muscle pains. CONCLUSION: Piggery workers and pigs in study area were free of Influenza-A (H1, H3, H5) viruses. The current practices of the piggery workers should be encouraged.",2013 Nov 17,"['Awosanya, Emmanuel Jolaoluwa', 'Ogundipe, Gabriel', 'Babalobi, Olutayo', 'Omilabu, Sunday']",Pan Afr Med J,,,True
45b4b6a49cc3373b0f67b014910073336dbca667,PMC,RNase L restricts the mobility of engineered retrotransposons in cultured human cells,http://dx.doi.org/10.1093/nar/gkt1308,PMC3973342,24371271,CC BY,"Retrotransposons are mobile genetic elements, and their mobility can lead to genomic instability. Retrotransposon insertions are associated with a diverse range of sporadic diseases, including cancer. Thus, it is not a surprise that multiple host defense mechanisms suppress retrotransposition. The 2′,5′-oligoadenylate (2-5A) synthetase (OAS)-RNase L system is a mechanism for restricting viral infections during the interferon antiviral response. Here, we investigated a potential role for the OAS-RNase L system in the restriction of retrotransposons. Expression of wild type (WT) and a constitutively active form of RNase L (NΔ385), but not a catalytically inactive RNase L mutant (R667A), impaired the mobility of engineered human LINE-1 (L1) and mouse intracisternal A-type particle retrotransposons in cultured human cells. Furthermore, WT RNase L, but not an inactive RNase L mutant (R667A), reduced L1 RNA levels and subsequent expression of the L1-encoded proteins (ORF1p and ORF2p). Consistently, confocal immunofluorescent microscopy demonstrated that WT RNase L, but not RNase L R667A, prevented formation of L1 cytoplasmic foci. Finally, siRNA-mediated depletion of endogenous RNase L in a human ovarian cancer cell line (Hey1b) increased the levels of L1 retrotransposition by ∼2-fold. Together, these data suggest that RNase L might function as a suppressor of structurally distinct retrotransposons.",2014 Apr 25,"['Zhang, Ao', 'Dong, Beihua', 'Doucet, Aurélien J.', 'Moldovan, John B.', 'Moran, John V.', 'Silverman, Robert H.']",Nucleic Acids Res,,,True
88599257eafdc8f7994d42af5dca697fd9283dd4,PMC,RNase L restricts the mobility of engineered retrotransposons in cultured human cells,http://dx.doi.org/10.1093/nar/gkt1308,PMC3973342,24371271,CC BY,"Retrotransposons are mobile genetic elements, and their mobility can lead to genomic instability. Retrotransposon insertions are associated with a diverse range of sporadic diseases, including cancer. Thus, it is not a surprise that multiple host defense mechanisms suppress retrotransposition. The 2′,5′-oligoadenylate (2-5A) synthetase (OAS)-RNase L system is a mechanism for restricting viral infections during the interferon antiviral response. Here, we investigated a potential role for the OAS-RNase L system in the restriction of retrotransposons. Expression of wild type (WT) and a constitutively active form of RNase L (NΔ385), but not a catalytically inactive RNase L mutant (R667A), impaired the mobility of engineered human LINE-1 (L1) and mouse intracisternal A-type particle retrotransposons in cultured human cells. Furthermore, WT RNase L, but not an inactive RNase L mutant (R667A), reduced L1 RNA levels and subsequent expression of the L1-encoded proteins (ORF1p and ORF2p). Consistently, confocal immunofluorescent microscopy demonstrated that WT RNase L, but not RNase L R667A, prevented formation of L1 cytoplasmic foci. Finally, siRNA-mediated depletion of endogenous RNase L in a human ovarian cancer cell line (Hey1b) increased the levels of L1 retrotransposition by ∼2-fold. Together, these data suggest that RNase L might function as a suppressor of structurally distinct retrotransposons.",2014 Apr 25,"['Zhang, Ao', 'Dong, Beihua', 'Doucet, Aurélien J.', 'Moldovan, John B.', 'Moran, John V.', 'Silverman, Robert H.']",Nucleic Acids Res,,,False
ab98d1b125aa0704e63adef426b27abd32e935f0,PMC,"Full Genome Virus Detection in Fecal Samples Using Sensitive Nucleic Acid Preparation, Deep Sequencing, and a Novel Iterative Sequence Classification Algorithm",http://dx.doi.org/10.1371/journal.pone.0093269,PMC3973683,24695106,CC BY,"We have developed a full genome virus detection process that combines sensitive nucleic acid preparation optimised for virus identification in fecal material with Illumina MiSeq sequencing and a novel post-sequencing virus identification algorithm. Enriched viral nucleic acid was converted to double-stranded DNA and subjected to Illumina MiSeq sequencing. The resulting short reads were processed with a novel iterative Python algorithm SLIM for the identification of sequences with homology to known viruses. De novo assembly was then used to generate full viral genomes. The sensitivity of this process was demonstrated with a set of fecal samples from HIV-1 infected patients. A quantitative assessment of the mammalian, plant, and bacterial virus content of this compartment was generated and the deep sequencing data were sufficient to assembly 12 complete viral genomes from 6 virus families. The method detected high levels of enteropathic viruses that are normally controlled in healthy adults, but may be involved in the pathogenesis of HIV-1 infection and will provide a powerful tool for virus detection and for analyzing changes in the fecal virome associated with HIV-1 progression and pathogenesis.",2014 Apr 2,"['Cotten, Matthew', 'Oude Munnink, Bas', 'Canuti, Marta', 'Deijs, Martin', 'Watson, Simon J.', 'Kellam, Paul', 'van der Hoek, Lia']",PLoS One,,,True
b8660d5f12c9a6a85b73207bc61291535c2700ce,PMC,Effect of cinnamon water extract on monocyte-to-macrophage differentiation and scavenger receptor activity,http://dx.doi.org/10.1186/1472-6882-14-90,PMC3973967,24602512,CC BY,"BACKGROUND: Water soluble cinnamon extract has been shown to increase insulin sensitivity and modulate macrophage activation, a desirable trait for the management of obesity or atherosclerosis. Our present study investigated whether cinnamon water extract (CWE) may influence the differentiation of monocytes into macrophages and the activity of macrophage scavenger receptors, commonly observed in atherosclerotic lesions. METHODS: We investigated the effect of CWE on the expression of various surface markers and the uptake of acetylated low density lipoprotein (LDL) in phorbol-12-myristate-13-acetate (PMA)-stimulated THP-1 cells. The protein levels of PMA or macrophage-colony stimulating factor (M-CSF)-stimulated type 1 macrophage scavenger receptor (SRA) were analyzed. Finally, the role of extracellar signal-related kinase (ERK) 1/2 in SRA synthesis and the effect of CWE on PMA-stimulated ERK1/2 were determined. RESULTS: CWE inhibited the differentiation of monocyte by decreasing the expression of CD11b, CD36 and SRA and the uptake of acetyl LDL. CWE suppressed the upregulation of SRA by M-CSF and modulated ERK1/2 activity, which was required for PMA-induced SRA synthesis. CONCLUSIONS: Our results demonstrate that CWE was able to interfere with monocyte differentiation and macrophage scavenger activity, indicating its potential in preventing the development of atherosclerotic lesions.",2014 Mar 7,"['Kang, Hee', 'Park, Sung-Hyun', 'Yun, Jeong-Moon', 'Nam, Tae-Gyu', 'Kim, Young-Eun', 'Kim, Dae-Ok', 'Kim, Youn Jung']",BMC Complement Altern Med,,,True
d2c72e2daceccd9b61cb182d778661e29256527b,PMC,Natural reservoirs for homologs of hepatitis C virus,http://dx.doi.org/10.1038/emi.2014.19,PMC3974340,26038514,CC BY,"Hepatitis C virus is considered a major public health problem, infecting 2%–3% of the human population. Hepatitis C virus infection causes acute and chronic liver disease, including chronic hepatitis, cirrhosis and hepatocellular carcinoma. In fact, hepatitis C virus infection is the most frequent indication for liver transplantation and a vaccine is not available. Hepatitis C virus displays a narrow host species tropism, naturally infecting only humans, although chimpanzees are also susceptible to experimental infection. To date, there is no evidence for an animal reservoir of viruses closely related to hepatitis C virus which may have crossed the species barrier to cause disease in humans and resulted in the current pandemic. In fact, due to this restricted host range, a robust immunocompetent small animal model is still lacking, hampering mechanistic analysis of virus pathogenesis, immune control and prophylactic vaccine development. Recently, several studies discovered new viruses related to hepatitis C virus, belonging to the hepaci- and pegivirus genera, in small wild mammals (rodents and bats) and domesticated animals which live in close contact with humans (dogs and horses). Genetic and biological characterization of these newly discovered hepatitis C virus-like viruses infecting different mammals will contribute to our understanding of the origins of hepatitis C virus in humans and enhance our ability to study pathogenesis and immune responses using tractable animal models. In this review article, we start with an introduction on the genetic diversity of hepatitis C virus and then focus on the newly discovered viruses closely related to hepatitis C virus. Finally, we discuss possible theories about the origin of this important viral human pathogen.",2014 Mar 26,"['Pfaender, Stephanie', 'Brown, Richard JP', 'Pietschmann, Thomas', 'Steinmann, Eike']",Emerg Microbes Infect,,,True
cf750714decab335f8990db7d0ca100506fa99fa,PMC,Novel Coronavirus and Astrovirus in Delaware Bay Shorebirds,http://dx.doi.org/10.1371/journal.pone.0093395,PMC3974748,24699424,CC BY,"BACKGROUND: Wild birds are an important but to some extent under-studied reservoir for emerging pathogens. We used unbiased sequencing methods for virus discovery in shorebird samples from the Delaware Bay, USA; an important feeding ground for thousands of migratory birds. FINDINGS: Analysis of shorebird fecal samples indicated the presence of a novel astrovirus and coronavirus. A sanderling sample yielded sequences with distant homology to avian nephritis virus 1, an astrovirus associated with acute nephritis in poultry. A ruddy turnstone sample yielded sequences with homology to deltacoronaviruses. CONCLUSIONS: Our findings highlight shorebirds as a virus reservoir and the need to closely monitor wild bird populations for the emergence of novel virus variants.",2014 Apr 3,"['Honkavuori, Kirsi S.', 'Briese, Thomas', 'Krauss, Scott', 'Sanchez, Maria D.', 'Jain, Komal', 'Hutchison, Stephen K.', 'Webster, Robert G.', 'Lipkin, W. Ian']",PLoS One,,,True
db80870c75793687f024d74e11d6a6d49333b1b6,PMC,Deep Sequencing to Identify the Causes of Viral Encephalitis,http://dx.doi.org/10.1371/journal.pone.0093993,PMC3974838,24699691,CC BY,"Deep sequencing allows for a rapid, accurate characterization of microbial DNA and RNA sequences in many types of samples. Deep sequencing (also called next generation sequencing or NGS) is being developed to assist with the diagnosis of a wide variety of infectious diseases. In this study, seven frozen brain samples from deceased subjects with recent encephalitis were investigated. RNA from each sample was extracted, randomly reverse transcribed and sequenced. The sequence analysis was performed in a blinded fashion and confirmed with pathogen-specific PCR. This analysis successfully identified measles virus sequences in two brain samples and herpes simplex virus type-1 sequences in three brain samples. No pathogen was identified in the other two brain specimens. These results were concordant with pathogen-specific PCR and partially concordant with prior neuropathological examinations, demonstrating that deep sequencing can accurately identify viral infections in frozen brain tissue.",2014 Apr 3,"['Chan, Benjamin K.', 'Wilson, Theodore', 'Fischer, Kael F.', 'Kriesel, John D.']",PLoS One,,,True
dcef588534b114e24a8c93a3eeeba8c1d11dd8a3,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,True
43c5fd0ced20ca85ba8a50b829674b806efb390d,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
b2cadb48524929ff83ac9705cb1d0a747b5bb1e8,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
93f839ddebf73ec46b504aafff560f7b3b50f22e,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
da0263344c5e5a938ffa955c8c6a2b9a12f8db6e,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
dae759b41afa898455c421249fda604375d8c973,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
d6043608d84c9697099d1e554487278e735942d2,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
2a70ba4400d14058b87d05736cf93bac434a01be,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
17815ef0b4f84d574710ea853ddfedb3b885dc69,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
07c02024be63150bd34d668fa5381061c23f07db,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
ba4c7eec34d93bb53325e6d925cb79ad04423cd1,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
b9a7147127a2c50c1d64f8e0236738301c534be0,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
a8d8faf148d930bc5d0b5908b0069c770123109e,PMC,A Human Lung Xenograft Mouse Model of Nipah Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1004063,PMC3974875,24699832,CC BY,"Nipah virus (NiV) is a member of the genus Henipavirus (family Paramyxoviridae) that causes severe and often lethal respiratory illness and encephalitis in humans with high mortality rates (up to 92%). NiV can cause Acute Lung Injury (ALI) in humans, and human-to-human transmission has been observed in recent outbreaks of NiV. While the exact route of transmission to humans is not known, we have previously shown that NiV can efficiently infect human respiratory epithelial cells. The molecular mechanisms of NiV-associated ALI in the human respiratory tract are unknown. Thus, there is an urgent need for models of henipavirus infection of the human respiratory tract to study the pathogenesis and understand the host responses. Here, we describe a novel human lung xenograft model in mice to study the pathogenesis of NiV. Following transplantation, human fetal lung xenografts rapidly graft and develop mature structures of adult lungs including cartilage, vascular vessels, ciliated pseudostratified columnar epithelium, and primitive “air” spaces filled with mucus and lined by cuboidal to flat epithelium. Following infection, NiV grows to high titers (10(7) TCID(50)/gram lung tissue) as early as 3 days post infection (pi). NiV targets both the endothelium as well as respiratory epithelium in the human lung tissues, and results in syncytia formation. NiV infection in the human lung results in the production of several cytokines and chemokines including IL-6, IP-10, eotaxin, G-CSF and GM-CSF on days 5 and 7 pi. In conclusion, this study demonstrates that NiV can replicate to high titers in a novel in vivo model of the human respiratory tract, resulting in a robust inflammatory response, which is known to be associated with ALI. This model will facilitate progress in the fundamental understanding of henipavirus pathogenesis and virus-host interactions; it will also provide biologically relevant models for other respiratory viruses.",2014 Apr 3,"['Valbuena, Gustavo', 'Halliday, Hailey', 'Borisevich, Viktoriya', 'Goez, Yenny', 'Rockx, Barry']",PLoS Pathog,,,True
ee55aea26f816403476a7cb71816b8ecb1110329,PMC,iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking,http://dx.doi.org/10.3390/ijms15034915,PMC3975431,24651462,CC BY,"Nuclear receptors (NRs) are closely associated with various major diseases such as cancer, diabetes, inflammatory disease, and osteoporosis. Therefore, NRs have become a frequent target for drug development. During the process of developing drugs against these diseases by targeting NRs, we are often facing a problem: Given a NR and chemical compound, can we identify whether they are really in interaction with each other in a cell? To address this problem, a predictor called “iNR-Drug” was developed. In the predictor, the drug compound concerned was formulated by a 256-D (dimensional) vector derived from its molecular fingerprint, and the NR by a 500-D vector formed by incorporating its sequential evolution information and physicochemical features into the general form of pseudo amino acid composition, and the prediction engine was operated by the SVM (support vector machine) algorithm. Compared with the existing prediction methods in this area, iNR-Drug not only can yield a higher success rate, but is also featured by a user-friendly web-server established at http://www.jci-bioinfo.cn/iNR-Drug/, which is particularly useful for most experimental scientists to obtain their desired data in a timely manner. It is anticipated that the iNR-Drug server may become a useful high throughput tool for both basic research and drug development, and that the current approach may be easily extended to study the interactions of drug with other targets as well.",2014 Mar 19,"['Fan, Yue-Nong', 'Xiao, Xuan', 'Min, Jian-Liang', 'Chou, Kuo-Chen']",Int J Mol Sci,,,True
ceb581975a05b3e74dc49c8efe7abffb656f6c69,PMC,iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking,http://dx.doi.org/10.3390/ijms15034915,PMC3975431,24651462,CC BY,"Nuclear receptors (NRs) are closely associated with various major diseases such as cancer, diabetes, inflammatory disease, and osteoporosis. Therefore, NRs have become a frequent target for drug development. During the process of developing drugs against these diseases by targeting NRs, we are often facing a problem: Given a NR and chemical compound, can we identify whether they are really in interaction with each other in a cell? To address this problem, a predictor called “iNR-Drug” was developed. In the predictor, the drug compound concerned was formulated by a 256-D (dimensional) vector derived from its molecular fingerprint, and the NR by a 500-D vector formed by incorporating its sequential evolution information and physicochemical features into the general form of pseudo amino acid composition, and the prediction engine was operated by the SVM (support vector machine) algorithm. Compared with the existing prediction methods in this area, iNR-Drug not only can yield a higher success rate, but is also featured by a user-friendly web-server established at http://www.jci-bioinfo.cn/iNR-Drug/, which is particularly useful for most experimental scientists to obtain their desired data in a timely manner. It is anticipated that the iNR-Drug server may become a useful high throughput tool for both basic research and drug development, and that the current approach may be easily extended to study the interactions of drug with other targets as well.",2014 Mar 19,"['Fan, Yue-Nong', 'Xiao, Xuan', 'Min, Jian-Liang', 'Chou, Kuo-Chen']",Int J Mol Sci,,,False
b3e1d993fd5eb9e538a5acb4f5933d4bb6209878,PMC,Estimating the incidence reporting rates of new influenza pandemics at an early stage using travel data from the source country,http://dx.doi.org/10.1017/S0950268813002550,PMC3975527,24107289,CC BY,"During the surveillance of influenza pandemics, underreported data are a public health challenge that complicates the understanding of pandemic threats and can undermine mitigation efforts. We propose a method to estimate incidence reporting rates at early stages of new influenza pandemics using 2009 pandemic H1N1 as an example. Routine surveillance data and statistics of travellers arriving from Mexico were used. Our method incorporates changes in reporting rates such as linearly increasing trends due to the enhanced surveillance. From our results, the reporting rate was estimated at 0·46% during early stages of the pandemic in Mexico. We estimated cumulative incidence in the Mexican population to be 0·7% compared to 0·003% reported by officials in Mexico at the end of April. This method could be useful in estimation of actual cases during new influenza pandemics for policy makers to better determine appropriate control measures.",2014 May 10,"['CHONG, K. C.', 'FONG, H. F.', 'ZEE, C. Y.']",Epidemiol Infect,,,True
595019b82939f4fc62cda92fe6eedd34f6933c35,PMC,Aspergillus spp. colonization in exhaled breath condensate of lung cancer patients from Puglia Region of Italy,http://dx.doi.org/10.1186/1471-2466-14-22,PMC3975946,24548615,CC BY,"BACKGROUND: Airways of lung cancer patients are often colonized by fungi. Some of these colonizing fungi, under particular conditions, produce cancerogenic mycotoxins. Given the recent interest in the infective origin of lung cancer, with this preliminary study we aim to give our small contribution to this field of research by analysing the fungal microbiome of the exhaled breath condensate of lung cancer patients from Puglia, a region of Italy. METHODS: We enrolled 43 lung cancer patients and 21 healthy subjects that underwent exhaled breath condensate and bronchial brushing collection. The fungal incidence and nature of sample collected were analysed by using a selected media for Aspergillus species. RESULTS: For the first time we were able to analyse the fungal microbioma of the exhaled breath condensate. 27.9% of lung cancer patients showed a presence of Aspergillus niger, or A. ochraceus or Penicillium ssp. while none of the healthy subjects did so. CONCLUSION: The results confirmed the high percentage of fungal colonization of the airways of lung cancer patients from Puglia, suggesting the need to conduct further analyses in this field in order to evaluate the exact pathogenetic role of these fungi in lung cancer as well as to propose efficient, empirical therapy.",2014 Feb 18,"['Carpagnano, Giovanna E', 'Lacedonia, Donato', 'Palladino, Grazia Pia', 'Logrieco, Giuseppe', 'Crisetti, Elisabetta', 'Susca, Antonia', 'Logrieco, Antonio', 'Foschino-Barbaro, Maria P']",BMC Pulm Med,,,True
b45e94d7cf1a4ac89b45053ce5a24f03984f8e24,PMC,Association of Radiologic Findings with Mortality in Patients with Avian Influenza H7N9 Pneumonia,http://dx.doi.org/10.1371/journal.pone.0093885,PMC3976364,24705783,CC BY,"BACKGROUND: The novel H7N9 virus causes severe illness, including pneumonia and acute respiratory distress syndrome, with high rates of mortality. We investigated the association of initial radiologic characteristics obtained at admission with clinical outcomes in patients with avian influenza H7N9 pneumonia. METHODS: Demographics, comorbidities, clinical findings, radiologic appearance and scores of the affected lung parenchyma were compared between survivor group (n = 15) and mortality group (n = 7). Two radiologic scores were calculated, one using chest radiography and one using CT. Follow-up CT scans at discharge were analyzed in 12 patients of the survival group. RESULTS: All the patients in mortality group developed acute respiratory distress syndrome and required mechanical ventilation, while in the survival group 33% (5/15) developed acute respiratory distress syndrome (P<0.05) and 27% (4/15) required mechanical ventilation (P<0.05). The mean radiographic and CT scores of the mortality group were 50% higher compared to the survival group (P<0.05). ROC analysis revealed an area under curve of 0.738 for the radiographic score with an optimal cutoff value of a score of 19 for prediction of mortality, with a sensitivity of 71% and a specificity of 67%, and an area under curve of 0.833 for the CT score with an optimal cutoff value of a CT score of 21 for prediction of mortality, with a sensitivity of 86% and a specificity of 73%. The mean CT score of the affected lung parenchyma at discharge was 30% lower than the initial CT examination (P<0.05). CONCLUSION: High initial radiologic score is associated with mortality in patients with avian influenza H7N9 pneumonia.",2014 Apr 4,"['Feng, Feng', 'Jiang, Yebin', 'Yuan, Min', 'Shen, Jie', 'Yin, Huabin', 'Geng, Daoying', 'Xu, Jianrong', 'Hua, Yanqing', 'Shi, Jingyun', 'Shi, Yuxin', 'Zhang, Zhiyong']",PLoS One,,,True
ce48c5f903bc1435190dd7ddf21612cb0a8b0815,PMC,"Establishing and Applying a Schistosomiasis Early Warning Index (SEWI) in the Lower Yangtze River Region of Jiangsu Province, China",http://dx.doi.org/10.1371/journal.pone.0094012,PMC3976384,24705352,CC BY,"BACKGROUND: China has made remarkable progress in schistosomiasis control over the past decades. Transmission control has replaced morbidity control as the country moves towards the goal of elimination and the current challenge is to find a sensitive measure capable of gauging transmission risk in low-prevalence areas. The study aims to develop a Schistosomiasis Early Warning Index (SEWI) and demonstrate its use in Jiangsu Province along the lower Yangtze River. METHODOLOGY/PRINCIPAL FINDINGS: The Delphi approach, a structured communication technique, was used to develop the SEWI. Two rounds of interviews with 30 public health experts specialized in schistosomiasis control were conducted using 40 indicators that reflected different aspects of schistosomiasis transmission and control. The necessity, feasibility, and sensitivity of each indicator were assessed and the weight value of each indicator determined based on these experts' judgment. The system included 3 first-order indicators, 7 second-order indicators, and 30 third-order indicators. The 3 first-order indicators were endemic status, control measures, social and environmental factors, with the weight values 0.366, 0.343 and 0.291, respectively. For the 7 second-order indicators, the highest weight value was for control measures for snails (0.175) and the lowest for transmission route (0.110). We estimated and mapped the SEWI for endemic areas at the county scale in Jiangsu Province finding that the majority of the endemic areas were characterized as medium transmission risk (SEWI risk values between 0.3 and 0.6), while areas where transmission interruption had been officially declared showed SEWI values <0.30. A few isolated areas (e.g. endemic islands in the Yangtze River) produced SEWI values >0.60. These estimates are largely in agreement with the endemicity levels based on recent epidemiological surveys. CONCLUSIONS/SIGNIFICANCE: The SEWI should be useful for estimation of schistosomiasis transmission surveillance, particularly with reference to the elimination of the disease in China.",2014 Apr 4,"['Yang, Kun', 'Xu, Jun-Fang', 'Zhang, Jian-Feng', 'Li, Wei', 'He, Jian', 'Liang, Song', 'Bergquist, Robert']",PLoS One,,,True
96c886c9234855e0fb6ef46ea3c5b7c1c7abc652,PMC,In Silico Analysis Reveals Sequential Interactions and Protein Conformational Changes during the Binding of Chemokine CXCL-8 to Its Receptor CXCR1,http://dx.doi.org/10.1371/journal.pone.0094178,PMC3976404,24705928,CC BY,"Chemokine CXCL-8 plays a central role in human immune response by binding to and activate its cognate receptor CXCR1, a member of the G-protein coupled receptor (GPCR) family. The full-length structure of CXCR1 is modeled by combining the structures of previous NMR experiments with those from homology modeling. Molecular docking is performed to search favorable binding sites of monomeric and dimeric CXCL-8 with CXCR1 and a mutated form of it. The receptor-ligand complex is embedded into a lipid bilayer and used in multi ns molecular dynamics (MD) simulations. A multi-steps binding mode is proposed: (i) the N-loop of CXCL-8 initially binds to the N-terminal domain of receptor CXCR1 driven predominantly by electrostatic interactions; (ii) hydrophobic interactions allow the N-terminal Glu-Leu-Arg (ELR) motif of CXCL-8 to move closer to the extracellular loops of CXCR1; (iii) electrostatic interactions finally dominate the interaction between the N-terminal ELR motif of CXCL-8 and the EC-loops of CXCR1. Mutation of CXCR1 abrogates this mode of binding. The detailed binding process may help to facilitate the discovery of agonists and antagonists for rational drug design.",2014 Apr 4,"['Liou, Je-Wen', 'Chang, Fang-Tzu', 'Chung, Yi', 'Chen, Wen-Yi', 'Fischer, Wolfgang B.', 'Hsu, Hao-Jen']",PLoS One,,,True
23696844593c72dd8c4d74607ff26049336fe9b0,PMC,Geographic Access to High Capability Severe Acute Respiratory Failure Centers in the United States,http://dx.doi.org/10.1371/journal.pone.0094057,PMC3976413,24705417,CC BY,"OBJECTIVE: Optimal care of adults with severe acute respiratory failure requires specific resources and expertise. We sought to measure geographic access to these centers in the United States. DESIGN: Cross-sectional analysis of geographic access to high capability severe acute respiratory failure centers in the United States. We defined high capability centers using two criteria: (1) provision of adult extracorporeal membrane oxygenation (ECMO), based on either 2008–2013 Extracorporeal Life Support Organization reporting or provision of ECMO to 2010 Medicare beneficiaries; or (2) high annual hospital mechanical ventilation volume, based 2010 Medicare claims. SETTING: Nonfederal acute care hospitals in the United States. MEASUREMENTS AND MAIN RESULTS: We defined geographic access as the percentage of the state, region and national population with either direct or hospital-transferred access within one or two hours by air or ground transport. Of 4,822 acute care hospitals, 148 hospitals met our ECMO criteria and 447 hospitals met our mechanical ventilation criteria. Geographic access varied substantially across states and regions in the United States, depending on center criteria. Without interhospital transfer, an estimated 58.5% of the national adult population had geographic access to hospitals performing ECMO and 79.0% had geographic access to hospitals performing a high annual volume of mechanical ventilation. With interhospital transfer and under ideal circumstances, an estimated 96.4% of the national adult population had geographic access to hospitals performing ECMO and 98.6% had geographic access to hospitals performing a high annual volume of mechanical ventilation. However, this degree of geographic access required substantial interhospital transfer of patients, including up to two hours by air. CONCLUSIONS: Geographic access to high capability severe acute respiratory failure centers varies widely across states and regions in the United States. Adequate referral center access in the case of disasters and pandemics will depend highly on local and regional care coordination across political boundaries.",2014 Apr 4,"['Wallace, David J.', 'Angus, Derek C.', 'Seymour, Christopher W.', 'Yealy, Donald M.', 'Carr, Brendan G.', 'Kurland, Kristen', 'Boujoukos, Arthur', 'Kahn, Jeremy M.']",PLoS One,,,True
2b8c0be4a3bed5dbeea46401dcebe6c1263ead10,PMC,Decline in temperature and humidity increases the occurrence of influenza in cold climate,http://dx.doi.org/10.1186/1476-069X-13-22,PMC3978084,24678699,CC BY,"BACKGROUND: Both temperature and humidity may independently or jointly contribute to the risk of influenza infections. We examined the relations between the level and decrease of temperature, humidity and the risk of influenza A and B virus infections in a subarctic climate. METHODS: We conducted a case-crossover study among military conscripts (n = 892) seeking medical attention due to respiratory symptoms during their military training period and identified 66 influenza A and B cases by PCR or serology. Meteorological data such as measures of average and decline in ambient temperature and absolute humidity (AH) during the three preceding days of the onset (hazard period) and two reference periods, prior and after the onset were obtained. RESULTS: The average temperature preceding the influenza onset was −6.8 ± 5.6°C and AH 3.1 ± 1.3 g/m(3). A decrease in both temperature and AH during the hazard period increased the occurrence of influenza so that a 1°C decrease in temperature and 0.5 g decrease per m(3) in AH increased the estimated risk by 11% [OR 1.11 (1.03 to 1.20)] and 58% [OR 1.58 (1.28 to 1.96)], respectively. The occurrence of influenza infections was positively associated with both the average temperature [OR 1.10 per 1°C (95% confidence interval 1.02 to 1.19)] and AH [OR 1.25 per g/m(3) (1.05 to 1.49)] during the hazard period prior to onset. CONCLUSION: Our results demonstrate that a decrease rather than low temperature and humidity per se during the preceding three days increase the risk of influenza episodes in a cold climate.",2014 Mar 28,"['Jaakkola, Kari', 'Saukkoriipi, Annika', 'Jokelainen, Jari', 'Juvonen, Raija', 'Kauppila, Jaana', 'Vainio, Olli', 'Ziegler, Thedi', 'Rönkkö, Esa', 'Jaakkola, Jouni JK', 'Ikäheimo, Tiina M']",Environ Health,,,True
efaa556b484fbcd9cc34832ffac53ef3e834e9c0,PMC,Mucosal Vaccination with Recombinant Lactobacillus casei-Displayed CTA1-Conjugated Consensus Matrix Protein-2 (sM2) Induces Broad Protection against Divergent Influenza Subtypes in BALB/c Mice,http://dx.doi.org/10.1371/journal.pone.0094051,PMC3979752,24714362,CC BY,"To develop a safe and effective mucosal vaccine against pathogenic influenza viruses, we constructed recombinant Lactobacillus casei strains that express conserved matrix protein 2 with (pgsA-CTA1-sM2/L. casei) or without (pgsA-sM2/L. casei) cholera toxin subunit A1 (CTA1) on the surface. The surface localization of the fusion protein was verified by cellular fractionation analyses, flow cytometry and immunofluorescence microscopy. Oral and nasal inoculations of recombinant L. casei into mice resulted in high levels of serum immunoglobulin G (IgG) and mucosal IgA. However, the conjugation of cholera toxin subunit A1 induced more potent mucosal, humoral and cell-mediated immune responses. In a challenge test with 10 MLD(50) of A/EM/Korea/W149/06(H5N1), A/Puerto Rico/8/34(H1N1), A/Aquatic bird /Korea/W81/2005(H5N2), A/Aquatic bird/Korea/W44/2005(H7N3), and A/Chicken/Korea/116/2004(H9N2) viruses, the recombinant pgsA-CTA1-sM2/L. casei provided better protection against lethal challenges than pgsA-sM2/L. casei, pgsA/L. casei and PBS in mice. These results indicate that mucosal immunization with recombinant L. casei expressing CTA1-conjugated sM2 protein on its surface is an effective means of eliciting protective immune responses against diverse influenza subtypes.",2014 Apr 8,"['Chowdhury, Mohammed Y. E.', 'Li, Rui', 'Kim, Jae-Hoon', 'Park, Min-Eun', 'Kim, Tae-Hwan', 'Pathinayake, Prabuddha', 'Weeratunga, Prasanna', 'Song, Man Ki', 'Son, Hwa-Young', 'Hong, Seung-Pyo', 'Sung, Moon-Hee', 'Lee, Jong-Soo', 'Kim, Chul-Joong']",PLoS One,,,True
c6c0a0d35bdedb534df909619bd7f240f9d52ae6,PMC,The Nairovirus Nairobi Sheep Disease Virus/Ganjam Virus Induces the Translocation of Protein Disulphide Isomerase-Like Oxidoreductases from the Endoplasmic Reticulum to the Cell Surface and the Extracellular Space,http://dx.doi.org/10.1371/journal.pone.0094656,PMC3979861,24714576,CC BY,"Nairobi sheep disease virus (NSDV) of the genus Nairovirus causes a haemorrhagic gastroenteritis in sheep and goats with mortality up to 90%; the virus is found in East and Central Africa, and in India, where the virus is called Ganjam virus. NSDV is closely related to the human pathogen Crimean-Congo haemorrhagic fever virus, which also causes a haemorrhagic disease. As with other nairoviruses, replication of NSDV takes place in the cytoplasm and the new virus particles bud into the Golgi apparatus; however, the effect of viral replication on cellular compartments has not been studied extensively. We have found that the overall structure of the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment and the Golgi were unaffected by infection with NSDV. However, we observed that NSDV infection led to the loss of protein disulphide isomerase (PDI), an oxidoreductase present in the lumen of the endoplasmic reticulum (ER) and which assists during protein folding, from the ER. Further investigation showed that NSDV-infected cells have high levels of PDI at their surface, and PDI is also secreted into the culture medium of infected cells. Another chaperone from the PDI family, ERp57, was found to be similarly affected. Analysis of infected cells and expression of individual viral glycoproteins indicated that the NSDV PreGn glycoprotein is involved in redistribution of these soluble ER oxidoreductases. It has been suggested that extracellular PDI can activate integrins and tissue factor, which are involved respectively in pro-inflammatory responses and disseminated intravascular coagulation, both of which manifest in many viral haemorrhagic fevers. The discovery of enhanced PDI secretion from NSDV-infected cells may be an important finding for understanding the mechanisms underlying the pathogenicity of haemorrhagic nairoviruses.",2014 Apr 8,"['Lasecka, Lidia', 'Baron, Michael D.']",PLoS One,,,True
e0a2b2bc691434ef31983736806d4e558b222c92,PMC,The Regulation of Autophagy by Influenza A Virus,http://dx.doi.org/10.1155/2014/498083,PMC3980786,24779013,CC BY,"Influenza A virus is a dreadful pathogen of animals and humans, causing widespread infection and severe morbidity and mortality. It is essential to characterize the influenza A virus-host interaction and develop efficient counter measures against the viral infection. Autophagy is known as a catabolic process for the recycling of the cytoplasmic macromolecules. Recently, it has been shown that autophagy is a critical mechanism underlying the interaction between influenza A virus and its host. Autophagy can be induced by the infection with influenza A virus, which is considered as a necessary process for the viral proliferation, including the accumulation of viral elements during the replication of influenza A virus. On the other hand, influenza A virus can inhibit the autophagic formation via interaction with the autophagy-related genes (Atg) and signaling pathways. In addition, autophagy is involved in the influenza virus-regulated cell deaths, leading to significant changes in host apoptosis. Interestingly, the high pathogenic strains of influenza A virus, such as H5N1, stimulate autophagic cell death and appear to interplay with the autophagy in distinct ways as compared with low pathogenic strains. This review discusses the regulation of autophagy, an influenza A virus driven process.",2014 Mar 23,"['Zhang, Rong', 'Chi, Xiaojuan', 'Wang, Song', 'Qi, Baomin', 'Yu, Xiaoqiang', 'Chen, Ji-Long']",Biomed Res Int,,,True
0089aa4b17549b9774f13a9e2e12a84fc827d60b,PMC,The Domain-Specific and Temperature-Dependent Protein Misfolding Phenotype of Variant Medium-Chain acyl-CoA Dehydrogenase,http://dx.doi.org/10.1371/journal.pone.0093852,PMC3981736,24718418,CC BY,"The implementation of expanded newborn screening programs reduced mortality and morbidity in medium-chain acyl-CoA dehydrogenase deficiency (MCADD) caused by mutations in the ACADM gene. However, the disease is still potentially fatal. Missense induced MCADD is a protein misfolding disease with a molecular loss-of-function phenotype. Here we established a comprehensive experimental setup to analyze the structural consequences of eight ACADM missense mutations (p.Ala52Val, p.Tyr67His, p.Tyr158His, p.Arg206Cys, p.Asp266Gly, p.Lys329Glu, p.Arg334Lys, p.Arg413Ser) identified after newborn screening and linked the corresponding protein misfolding phenotype to the site of side-chain replacement with respect to the domain. With fever being the crucial risk factor for metabolic decompensation of patients with MCADD, special emphasis was put on the analysis of structural and functional derangements related to thermal stress. Based on protein conformation, thermal stability and kinetic stability, the molecular phenotype in MCADD depends on the structural region that is affected by missense-induced conformational changes with the central β-domain being particularly prone to structural derangement and destabilization. Since systematic classification of conformational derangements induced by ACADM mutations may be a helpful tool in assessing the clinical risk of patients, we scored the misfolding phenotype of the variants in comparison to p.Lys329Glu (K304E), the classical severe mutation, and p.Tyr67His (Y42H), discussed to be mild. Experiments assessing the impact of thermal stress revealed that mutations in the ACADM gene lower the temperature threshold at which MCAD loss-of-function occurs. Consequently, increased temperature as it occurs during intercurrent infections, significantly increases the risk of further conformational derangement and loss of function of the MCAD enzyme explaining the life-threatening clinical courses observed during fever episodes. Early and aggressive antipyretic treatment thus may be life-saving in patients suffering from MCADD.",2014 Apr 9,"['Jank, Johanna M.', 'Maier, Esther M.', 'Reiß, Dunja D.', 'Haslbeck, Martin', 'Kemter, Kristina F.', 'Truger, Marietta S.', 'Sommerhoff, Christian P.', 'Ferdinandusse, Sacha', 'Wanders, Ronald J.', 'Gersting, Søren W.', 'Muntau, Ania C.']",PLoS One,,,True
faad09d0c4532ac11d673b84f539be583e897df9,PMC,The Spatial Resolution of Epidemic Peaks,http://dx.doi.org/10.1371/journal.pcbi.1003561,PMC3983068,24722420,CC BY,"The emergence of novel respiratory pathogens can challenge the capacity of key health care resources, such as intensive care units, that are constrained to serve only specific geographical populations. An ability to predict the magnitude and timing of peak incidence at the scale of a single large population would help to accurately assess the value of interventions designed to reduce that peak. However, current disease-dynamic theory does not provide a clear understanding of the relationship between: epidemic trajectories at the scale of interest (e.g. city); population mobility; and higher resolution spatial effects (e.g. transmission within small neighbourhoods). Here, we used a spatially-explicit stochastic meta-population model of arbitrary spatial resolution to determine the effect of resolution on model-derived epidemic trajectories. We simulated an influenza-like pathogen spreading across theoretical and actual population densities and varied our assumptions about mobility using Latin-Hypercube sampling. Even though, by design, cumulative attack rates were the same for all resolutions and mobilities, peak incidences were different. Clear thresholds existed for all tested populations, such that models with resolutions lower than the threshold substantially overestimated population-wide peak incidence. The effect of resolution was most important in populations which were of lower density and lower mobility. With the expectation of accurate spatial incidence datasets in the near future, our objective was to provide a framework for how to use these data correctly in a spatial meta-population model. Our results suggest that there is a fundamental spatial resolution for any pathogen-population pair. If underlying interactions between pathogens and spatially heterogeneous populations are represented at this resolution or higher, accurate predictions of peak incidence for city-scale epidemics are feasible.",2014 Apr 10,"['Mills, Harriet L.', 'Riley, Steven']",PLoS Comput Biol,,,True
0d71c6368927c7235b7ab328d1ee33aebe699396,PMC,The Spatial Resolution of Epidemic Peaks,http://dx.doi.org/10.1371/journal.pcbi.1003561,PMC3983068,24722420,CC BY,"The emergence of novel respiratory pathogens can challenge the capacity of key health care resources, such as intensive care units, that are constrained to serve only specific geographical populations. An ability to predict the magnitude and timing of peak incidence at the scale of a single large population would help to accurately assess the value of interventions designed to reduce that peak. However, current disease-dynamic theory does not provide a clear understanding of the relationship between: epidemic trajectories at the scale of interest (e.g. city); population mobility; and higher resolution spatial effects (e.g. transmission within small neighbourhoods). Here, we used a spatially-explicit stochastic meta-population model of arbitrary spatial resolution to determine the effect of resolution on model-derived epidemic trajectories. We simulated an influenza-like pathogen spreading across theoretical and actual population densities and varied our assumptions about mobility using Latin-Hypercube sampling. Even though, by design, cumulative attack rates were the same for all resolutions and mobilities, peak incidences were different. Clear thresholds existed for all tested populations, such that models with resolutions lower than the threshold substantially overestimated population-wide peak incidence. The effect of resolution was most important in populations which were of lower density and lower mobility. With the expectation of accurate spatial incidence datasets in the near future, our objective was to provide a framework for how to use these data correctly in a spatial meta-population model. Our results suggest that there is a fundamental spatial resolution for any pathogen-population pair. If underlying interactions between pathogens and spatially heterogeneous populations are represented at this resolution or higher, accurate predictions of peak incidence for city-scale epidemics are feasible.",2014 Apr 10,"['Mills, Harriet L.', 'Riley, Steven']",PLoS Comput Biol,,,False
ce5e67e3d17645302f7a91d7d0c8bc3428884187,PMC,The Spatial Resolution of Epidemic Peaks,http://dx.doi.org/10.1371/journal.pcbi.1003561,PMC3983068,24722420,CC BY,"The emergence of novel respiratory pathogens can challenge the capacity of key health care resources, such as intensive care units, that are constrained to serve only specific geographical populations. An ability to predict the magnitude and timing of peak incidence at the scale of a single large population would help to accurately assess the value of interventions designed to reduce that peak. However, current disease-dynamic theory does not provide a clear understanding of the relationship between: epidemic trajectories at the scale of interest (e.g. city); population mobility; and higher resolution spatial effects (e.g. transmission within small neighbourhoods). Here, we used a spatially-explicit stochastic meta-population model of arbitrary spatial resolution to determine the effect of resolution on model-derived epidemic trajectories. We simulated an influenza-like pathogen spreading across theoretical and actual population densities and varied our assumptions about mobility using Latin-Hypercube sampling. Even though, by design, cumulative attack rates were the same for all resolutions and mobilities, peak incidences were different. Clear thresholds existed for all tested populations, such that models with resolutions lower than the threshold substantially overestimated population-wide peak incidence. The effect of resolution was most important in populations which were of lower density and lower mobility. With the expectation of accurate spatial incidence datasets in the near future, our objective was to provide a framework for how to use these data correctly in a spatial meta-population model. Our results suggest that there is a fundamental spatial resolution for any pathogen-population pair. If underlying interactions between pathogens and spatially heterogeneous populations are represented at this resolution or higher, accurate predictions of peak incidence for city-scale epidemics are feasible.",2014 Apr 10,"['Mills, Harriet L.', 'Riley, Steven']",PLoS Comput Biol,,,True
aa8fbab7c3255083bf78bcf8752b279ec210e684,PMC,The Spatial Resolution of Epidemic Peaks,http://dx.doi.org/10.1371/journal.pcbi.1003561,PMC3983068,24722420,CC BY,"The emergence of novel respiratory pathogens can challenge the capacity of key health care resources, such as intensive care units, that are constrained to serve only specific geographical populations. An ability to predict the magnitude and timing of peak incidence at the scale of a single large population would help to accurately assess the value of interventions designed to reduce that peak. However, current disease-dynamic theory does not provide a clear understanding of the relationship between: epidemic trajectories at the scale of interest (e.g. city); population mobility; and higher resolution spatial effects (e.g. transmission within small neighbourhoods). Here, we used a spatially-explicit stochastic meta-population model of arbitrary spatial resolution to determine the effect of resolution on model-derived epidemic trajectories. We simulated an influenza-like pathogen spreading across theoretical and actual population densities and varied our assumptions about mobility using Latin-Hypercube sampling. Even though, by design, cumulative attack rates were the same for all resolutions and mobilities, peak incidences were different. Clear thresholds existed for all tested populations, such that models with resolutions lower than the threshold substantially overestimated population-wide peak incidence. The effect of resolution was most important in populations which were of lower density and lower mobility. With the expectation of accurate spatial incidence datasets in the near future, our objective was to provide a framework for how to use these data correctly in a spatial meta-population model. Our results suggest that there is a fundamental spatial resolution for any pathogen-population pair. If underlying interactions between pathogens and spatially heterogeneous populations are represented at this resolution or higher, accurate predictions of peak incidence for city-scale epidemics are feasible.",2014 Apr 10,"['Mills, Harriet L.', 'Riley, Steven']",PLoS Comput Biol,,,True
91ff06254beef1b03a35520d4fd5bad025274b08,PMC,The Spatial Resolution of Epidemic Peaks,http://dx.doi.org/10.1371/journal.pcbi.1003561,PMC3983068,24722420,CC BY,"The emergence of novel respiratory pathogens can challenge the capacity of key health care resources, such as intensive care units, that are constrained to serve only specific geographical populations. An ability to predict the magnitude and timing of peak incidence at the scale of a single large population would help to accurately assess the value of interventions designed to reduce that peak. However, current disease-dynamic theory does not provide a clear understanding of the relationship between: epidemic trajectories at the scale of interest (e.g. city); population mobility; and higher resolution spatial effects (e.g. transmission within small neighbourhoods). Here, we used a spatially-explicit stochastic meta-population model of arbitrary spatial resolution to determine the effect of resolution on model-derived epidemic trajectories. We simulated an influenza-like pathogen spreading across theoretical and actual population densities and varied our assumptions about mobility using Latin-Hypercube sampling. Even though, by design, cumulative attack rates were the same for all resolutions and mobilities, peak incidences were different. Clear thresholds existed for all tested populations, such that models with resolutions lower than the threshold substantially overestimated population-wide peak incidence. The effect of resolution was most important in populations which were of lower density and lower mobility. With the expectation of accurate spatial incidence datasets in the near future, our objective was to provide a framework for how to use these data correctly in a spatial meta-population model. Our results suggest that there is a fundamental spatial resolution for any pathogen-population pair. If underlying interactions between pathogens and spatially heterogeneous populations are represented at this resolution or higher, accurate predictions of peak incidence for city-scale epidemics are feasible.",2014 Apr 10,"['Mills, Harriet L.', 'Riley, Steven']",PLoS Comput Biol,,,False
e572a3a154399f2b500b0f547a7252c94580acf4,PMC,Prediction of High Incidence of Dengue in the Philippines,http://dx.doi.org/10.1371/journal.pntd.0002771,PMC3983113,24722434,CC0,"BACKGROUND: Accurate prediction of dengue incidence levels weeks in advance of an outbreak may reduce the morbidity and mortality associated with this neglected disease. Therefore, models were developed to predict high and low dengue incidence in order to provide timely forewarnings in the Philippines. METHODS: Model inputs were chosen based on studies indicating variables that may impact dengue incidence. The method first uses Fuzzy Association Rule Mining techniques to extract association rules from these historical epidemiological, environmental, and socio-economic data, as well as climate data indicating future weather patterns. Selection criteria were used to choose a subset of these rules for a classifier, thereby generating a Prediction Model. The models predicted high or low incidence of dengue in a Philippines province four weeks in advance. The threshold between high and low was determined relative to historical incidence data. PRINCIPAL FINDINGS: Model accuracy is described by Positive Predictive Value (PPV), Negative Predictive Value (NPV), Sensitivity, and Specificity computed on test data not previously used to develop the model. Selecting a model using the F(0.5) measure, which gives PPV more importance than Sensitivity, gave these results: PPV = 0.780, NPV = 0.938, Sensitivity = 0.547, Specificity = 0.978. Using the F(3) measure, which gives Sensitivity more importance than PPV, the selected model had PPV = 0.778, NPV = 0.948, Sensitivity = 0.627, Specificity = 0.974. The decision as to which model has greater utility depends on how the predictions will be used in a particular situation. CONCLUSIONS: This method builds prediction models for future dengue incidence in the Philippines and is capable of being modified for use in different situations; for diseases other than dengue; and for regions beyond the Philippines. The Philippines dengue prediction models predicted high or low incidence of dengue four weeks in advance of an outbreak with high accuracy, as measured by PPV, NPV, Sensitivity, and Specificity.",2014 Apr 10,"['Buczak, Anna L.', 'Baugher, Benjamin', 'Babin, Steven M.', 'Ramac-Thomas, Liane C.', 'Guven, Erhan', 'Elbert, Yevgeniy', 'Koshute, Phillip T.', 'Velasco, John Mark S.', 'Roque, Vito G.', 'Tayag, Enrique A.', 'Yoon, In-Kyu', 'Lewis, Sheri H.']",PLoS Negl Trop Dis,,,True
b60f35d40ea356d450ec485223083150e662b10f,PMC,"Complete Genome Sequence of Strain SDCV/USA/Illinois121/2014, a Porcine Deltacoronavirus from the United States",http://dx.doi.org/10.1128/genomeA.00218-14,PMC3983293,24723704,CC BY,"To investigate the causative agent of swine diarrhea, next-generation sequencing (NGS) was performed on a porcine fecal sample. The NGS reads were assembled, which generated a complete swine Deltacoronavirus genome sequence, that of strain SDCV/USA/Illinois121/2014.",2014 Apr 10,"['Marthaler, Douglas', 'Jiang, Yin', 'Collins, Jim', 'Rossow, Kurt']",Genome Announc,,,True
4ebdb50f487a8f6c2421e3e3281b053990cb4fac,PMC,Full-Length Genome Sequence of Porcine Deltacoronavirus Strain USA/IA/2014/8734,http://dx.doi.org/10.1128/genomeA.00278-14,PMC3983307,24723718,CC BY,Porcine deltacoronavirus (PDCoV) was detected in feces from diarrheic sows during an epidemic of acute and transmissible diarrhea. No transmissible gastroenteritis virus or porcine epidemic diarrhea virus was detected. The PDCoV USA/IA/2014/8734 from the herd was sequenced for full-length genomic RNA to further characterize PDCoV in U.S. swine.,2014 Apr 10,"['Li, Ganwu', 'Chen, Qi', 'Harmon, Karen M.', 'Yoon, Kyoung-Jin', 'Schwartz, Kent J.', 'Hoogland, Marlin J.', 'Gauger, Phillip C.', 'Main, Rodger G.', 'Zhang, Jianqiang']",Genome Announc,,,True
c848bce30b9e60bccfd15a5534af1d0cea54c686,PMC,Thrombocytopenia Is Associated with Acute Respiratory Distress Syndrome Mortality: An International Study,http://dx.doi.org/10.1371/journal.pone.0094124,PMC3986053,24732309,CC BY,"BACKGROUND: Early detection of the Acute Respiratory Distress Syndrome (ARDS) has the potential to improvethe prognosis of critically ill patients admitted to the intensive care unit (ICU). However, no reliable biomarkers are currently available for accurate early detection of ARDS in patients with predisposing conditions. OBJECTIVES: This study examined risk factors and biomarkers for ARDS development and mortality in two prospective cohort studies. METHODS: We examined clinical risk factors for ARDS in a cohort of 178 patients in Beijing, China who were admitted to the ICU and were at high risk for ARDS. Identified biomarkers were then replicated in a second cohort of1,878 patients in Boston, USA. RESULTS: Of 178 patients recruited from participating hospitals in Beijing, 75 developed ARDS. After multivariate adjustment, sepsis (odds ratio [OR]:5.58, 95% CI: 1.70–18.3), pulmonary injury (OR: 3.22; 95% CI: 1.60–6.47), and thrombocytopenia, defined as platelet count <80×10(3)/µL, (OR: 2.67; 95% CI: 1.27–5.62)were significantly associated with increased risk of developing ARDS. Thrombocytopenia was also associated with increased mortality in patients who developed ARDS (adjusted hazard ratio [AHR]: 1.38, 95% CI: 1.07–1.57) but not in those who did not develop ARDS(AHR: 1.25, 95% CI: 0.96–1.62). The presence of both thrombocytopenia and ARDS substantially increased 60-daymortality. Sensitivity analyses showed that a platelet count of <100×10(3)/µLin combination with ARDS provide the highest prognostic value for mortality. These associations were replicated in the cohort of US patients. CONCLUSIONS: This study of ICU patients in both China and US showed that thrombocytopenia is associated with an increased risk of ARDS and platelet count in combination with ARDS had a high predictive value for patient mortality.",2014 Apr 14,"['Wang, Tiehua', 'Liu, Zhuang', 'Wang, Zhaoxi', 'Duan, Meili', 'Li, Gang', 'Wang, Shupeng', 'Li, Wenxiong', 'Zhu, Zhaozhong', 'Wei, Yongyue', 'Christiani, David C.', 'Li, Ang', 'Zhu, Xi']",PLoS One,,,True
bd592988022fb91de64e0d4c287d3b04d864f8ba,PMC,Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data,http://dx.doi.org/10.1371/journal.pone.0092199,PMC3986061,24732572,CC BY,"Laboratory testing is the single highest-volume medical activity, making it useful to ask how well one can anticipate whether a given test result will be high, low, or within the reference interval (“normal”). We analyzed 10 years of electronic health records—a total of 69.4 million blood tests—to see how well standard rule-mining techniques can anticipate test results based on patient age and gender, recent diagnoses, and recent laboratory test results. We evaluated rules according to their positive and negative predictive value (PPV and NPV) and area under the receiver-operator characteristic curve (ROC AUCs). Using a stringent cutoff of PPV and/or NPV≥0.95, standard techniques yield few rules for sendout tests but several for in-house tests, mostly for repeat laboratory tests that are part of the complete blood count and basic metabolic panel. Most rules were clinically and pathophysiologically plausible, and several seemed clinically useful for informing pre-test probability of a given result. But overall, rules were unlikely to be able to function as a general substitute for actually ordering a test. Improving laboratory utilization will likely require different input data and/or alternative methods.",2014 Apr 14,"['Mohammad, Fahim', 'Theisen-Toupal, Jesse C.', 'Arnaout, Ramy']",PLoS One,,,True
90706dd8b172f0aeb996ea828c356155c32e0682,PMC,"Anxiety, worry and cognitive risk estimate in relation to protective behaviors during the 2009 influenza A/H1N1 pandemic in Hong Kong: ten cross-sectional surveys",http://dx.doi.org/10.1186/1471-2334-14-169,PMC3986671,24674239,CC BY,"BACKGROUND: Few studies have investigated associations between psychological and behavioral indices throughout a major epidemic. This study was aimed to compare the strength of associations between different cognitive and affective measures of risk and self-reported protective behaviors in a series of ten cross-sectional surveys conducted throughout the first wave of influenza A/H1N1 pandemic. METHODS: All surveys were conducted using questionnaire-based telephone interviews, with random digit dialing to recruit adults from the general population. Measures of anxiety and worry (affective) and perceived risk (cognitive) regarding A/H1N1 were made in 10 serial surveys. Multivariate logistic regression models were used to estimate the cognitive/affective-behavioral associations in each survey while multilevel logistic models were conducted to estimate the average effects of each cognitive/affective measure on adoption of protective behaviors throughout the ten surveys. RESULTS: Excepting state anxiety, other affective measures including “anticipated worry”, “experienced worry” and “current worry” specific to A/H1N1 risk were consistently and strongly associated with adoption of protective behaviors across different survey periods. However, the cognitive-behavioral associations were weaker and inconsistent across the ten surveys. Perceived A/H1N1 severity relative to SARS had stronger associations with adoption of protective behaviors in the late epidemic periods than in the early epidemic periods. CONCLUSION: Risk-specific worries appear to be significantly associated with the adoption of protective behaviors at different epidemic stages, whereas cognitive measures may become more important in understanding people’s behavioral responses later in epidemics. Future epidemic-related psycho-behavioral research should include more affective-loaded measures of risk.",2014 Mar 27,"['Liao, Qiuyan', 'Cowling, Benjamin J', 'Lam, Wendy WT', 'Ng, Diane MW', 'Fielding, Richard']",BMC Infect Dis,,,True
b3f4cd3e21b32b677d50fda144e8eed9ee44df8e,PMC,High-dose dietary zinc oxide mitigates infection with transmissible gastroenteritis virus in piglets,http://dx.doi.org/10.1186/1746-6148-10-75,PMC3986850,24673930,CC BY,"BACKGROUND: Zinc (Zn) supplementation has been shown to reduce the incidence of diarrhea and to protect animals from intestinal diseases, but the mechanisms of this protective effect against virus infection in vivo have not yet been elucidated. Transmissible gastroenteritis virus (TGEV) causes diarrhea in piglets with an age-dependent decrease of severity. RESULTS: We used 60 weaned piglets that were divided into three groups to evaluate the effect of different Zn levels added to a conventional diet (50 mg Zn/kg diet, Zn(low), control group). The other groups received the diet supplemented with ZnO at final concentrations of 150 mg Zn/kg diet (Zn(med)), or 2,500 mg/kg diet (Zn(high)). Oral challenge infection with TGEV was performed when the pigs had been fed for 1 week with the respective diet. Half of the piglets of each group were sacrificed at day 1 and 18 after challenge infection. Fecal consistency was improved and body weights increased in the Zn(high) group when compared to the other groups, but no direct effect of Zn concentrations in the diet on fecal TGEV shedding and mucosal immune responses was detectable. However, in the Zn(high) group, we found a prevention of villus atrophy and decreased caspase-3-mediated apoptosis of jejunal epithelium. Furthermore, pigs receiving high Zn diet showed a down-regulation of interferon (IFN)-α, oligoadenylate synthetase (OAS), Zn transporter SLC39A4 (ZIP4), but up-regulation of metallothionein-1 (MT1), as well as the Zn transporters SLC30A1 (ZnT1) and SLC30A5 (ZnT5). In addition, forskolin-induced chloride secretion and epithelial resistance were controlled at a physiological level in the Zn(high) but not the other groups. Finally, in the Zn(high) group, we documented an earlier and higher systemic TGEV-specific serum antibody response. CONCLUSIONS: These results suggest that high dietary Zn could provide enhanced protection in the intestinal tract and stimulate the systemic humoral immune response against TGEV infection.",2014 Mar 28,"['Chai, Weidong', 'Zakrzewski, Silke S', 'Günzel, Dorothee', 'Pieper, Robert', 'Wang, Zhenya', 'Twardziok, Sven', 'Janczyk, Pawel', 'Osterrieder, Nikolaus', 'Burwinkel, Michael']",BMC Vet Res,,,True
9faf6a32a170b3fc5950af6a7d34cf710c79321d,PMC,"Gene silencing of β-galactosamide α-2,6-sialyltransferase 1 inhibits human influenza virus infection of airway epithelial cells",http://dx.doi.org/10.1186/1471-2180-14-78,PMC3986885,24670114,CC BY,"BACKGROUND: Human influenza virus hemagglutinin prefers to use sialic acid (SA) receptors via α-2,6 linkages. The β-galactoside α-2,6-sialyltransferase I (ST6Gal I) protein is encoded by the ST6GAL1 gene and is responsible for the addition of α-2,6 linked SA to the Galβ1-4GlcNAc disaccharide of glycans and glycoproteins found on the cellular surface. Therefore, ST6GAL1 could be a potential target for anti-influenza therapeutics. We used specific small interfering RNAs (siRNAs) to block expression of ST6GAL1 and limit distribution of SA receptors on the surface of airway epithelial cells. RESULTS: The siRNA duplexes we used inhibited ST6GAL1 mRNA expression and subsequent expression of the encoding protein. As a result, synthesis of α-2,6 SA galactose was inhibited. Adsorption of influenza virus particles to the surface of cells transfected with appropriate specific siRNAs was significantly reduced. Intracellular viral genome copy number and virus titer within the supernatant of cells transfected with siRNAs was significantly reduced in a dose-dependent manner compared with those for untransfected cells and cells transfected with non-specific siRNAs. CONCLUSIONS: We used siRNAs targeting ST6GAL1 to inhibit the expression of certain cell surface receptors, thereby preventing virus adsorption. This resulted in the inhibition of human influenza virus infection. Our findings are a significant development in the identification of potential new anti-influenza drug targets.",2014 Mar 27,"['Wu, Dong', 'Huang, Wenbo', 'Wang, Yutao', 'Guan, Wenda', 'Li, Runfeng', 'Yang, Zifeng', 'Zhong, Nanshan']",BMC Microbiol,,,True
b675d6df1216305b9f778bb8e8f9701fa3ff5ca9,PMC,"Gene silencing of β-galactosamide α-2,6-sialyltransferase 1 inhibits human influenza virus infection of airway epithelial cells",http://dx.doi.org/10.1186/1471-2180-14-78,PMC3986885,24670114,CC BY,"BACKGROUND: Human influenza virus hemagglutinin prefers to use sialic acid (SA) receptors via α-2,6 linkages. The β-galactoside α-2,6-sialyltransferase I (ST6Gal I) protein is encoded by the ST6GAL1 gene and is responsible for the addition of α-2,6 linked SA to the Galβ1-4GlcNAc disaccharide of glycans and glycoproteins found on the cellular surface. Therefore, ST6GAL1 could be a potential target for anti-influenza therapeutics. We used specific small interfering RNAs (siRNAs) to block expression of ST6GAL1 and limit distribution of SA receptors on the surface of airway epithelial cells. RESULTS: The siRNA duplexes we used inhibited ST6GAL1 mRNA expression and subsequent expression of the encoding protein. As a result, synthesis of α-2,6 SA galactose was inhibited. Adsorption of influenza virus particles to the surface of cells transfected with appropriate specific siRNAs was significantly reduced. Intracellular viral genome copy number and virus titer within the supernatant of cells transfected with siRNAs was significantly reduced in a dose-dependent manner compared with those for untransfected cells and cells transfected with non-specific siRNAs. CONCLUSIONS: We used siRNAs targeting ST6GAL1 to inhibit the expression of certain cell surface receptors, thereby preventing virus adsorption. This resulted in the inhibition of human influenza virus infection. Our findings are a significant development in the identification of potential new anti-influenza drug targets.",2014 Mar 27,"['Wu, Dong', 'Huang, Wenbo', 'Wang, Yutao', 'Guan, Wenda', 'Li, Runfeng', 'Yang, Zifeng', 'Zhong, Nanshan']",BMC Microbiol,,,False
d5f9caf3c407fae4690cd853b95d3c3e9b0a8b5e,PMC,"Disaster resilience in tertiary hospitals: a cross-sectional survey in Shandong Province, China",http://dx.doi.org/10.1186/1472-6963-14-135,PMC3987831,24661641,CC BY,"BACKGROUND: Hospital disaster resilience can be defined as a hospital’s ability to resist, absorb, and respond to the shock of disasters while maintaining critical functions, and then to recover to its original state or adapt to a new one. This study aims to explore the status of resilience among tertiary hospitals in Shandong Province, China. METHODS: A stratified random sample (n = 50) was derived from tertiary A, tertiary B, and tertiary C hospitals in Shandong Province, and was surveyed by questionnaire. Data on hospital characteristics and 8 key domains of hospital resilience were collected and analysed. Variables were binary, and analysed using descriptive statistics such as frequencies. RESULTS: A response rate of 82% (n = 41) was attained. Factor analysis identified four key factors from eight domains which appear to reflect the overall level of disaster resilience. These were hospital safety, disaster management mechanisms, disaster resources and disaster medical care capability. The survey demonstrated that in regard to hospital safety, 93% had syndromic surveillance systems for infectious diseases and 68% had evaluated their safety standards. In regard to disaster management mechanisms, all had general plans, while only 20% had specific plans for individual hazards. 49% had a public communication protocol and 43.9% attended the local coordination meetings. In regard to disaster resources, 75.6% and 87.5% stockpiled emergency drugs and materials respectively, while less than a third (30%) had a signed Memorandum of Understanding with other hospitals to share these resources. Finally in regard to medical care, 66% could dispatch an on-site medical rescue team, but only 5% had a ‘portable hospital’ function and 36.6% and 12% of the hospitals could surge their beds and staff capacity respectively. The average beds surge capacity within 1 day was 13%. CONCLUSIONS: This study validated the broad utility of a framework for understanding and measuring the level of hospital resilience. The survey demonstrated considerable variability in disaster resilience arrangements of tertiary hospitals in Shandong province, and the difference between tertiary A hospitals and tertiary B hospitals was also identified in essential areas.",2014 Mar 25,"['Zhong, Shuang', 'Hou, Xiang-Yu', 'Clark, Michele', 'Zang, Yu-Li', 'Wang, Lu', 'Xu, Ling-Zhong', 'FitzGerald, Gerard']",BMC Health Serv Res,,,True
4f2c063485df91923fc9c7c9f4ec6ebf5a61157a,PMC,"Model for Vaccine Design by Prediction of B-Epitopes of IEDB Given Perturbations in Peptide Sequence, In Vivo Process, Experimental Techniques, and Source or Host Organisms",http://dx.doi.org/10.1155/2014/768515,PMC3987976,24741624,CC BY,"Perturbation methods add variation terms to a known experimental solution of one problem to approach a solution for a related problem without known exact solution. One problem of this type in immunology is the prediction of the possible action of epitope of one peptide after a perturbation or variation in the structure of a known peptide and/or other boundary conditions (host organism, biological process, and experimental assay). However, to the best of our knowledge, there are no reports of general-purpose perturbation models to solve this problem. In a recent work, we introduced a new quantitative structure-property relationship theory for the study of perturbations in complex biomolecular systems. In this work, we developed the first model able to classify more than 200,000 cases of perturbations with accuracy, sensitivity, and specificity >90% both in training and validation series. The perturbations include structural changes in >50000 peptides determined in experimental assays with boundary conditions involving >500 source organisms, >50 host organisms, >10 biological process, and >30 experimental techniques. The model may be useful for the prediction of new epitopes or the optimization of known peptides towards computational vaccine design.",2014 Jan 12,"['González-Díaz, Humberto', 'Pérez-Montoto, Lázaro G.', 'Ubeira, Florencio M.']",J Immunol Res,,,False
a0f4a467be80972f434dabf027d2b5260b608740,PMC,"Model for Vaccine Design by Prediction of B-Epitopes of IEDB Given Perturbations in Peptide Sequence, In Vivo Process, Experimental Techniques, and Source or Host Organisms",http://dx.doi.org/10.1155/2014/768515,PMC3987976,24741624,CC BY,"Perturbation methods add variation terms to a known experimental solution of one problem to approach a solution for a related problem without known exact solution. One problem of this type in immunology is the prediction of the possible action of epitope of one peptide after a perturbation or variation in the structure of a known peptide and/or other boundary conditions (host organism, biological process, and experimental assay). However, to the best of our knowledge, there are no reports of general-purpose perturbation models to solve this problem. In a recent work, we introduced a new quantitative structure-property relationship theory for the study of perturbations in complex biomolecular systems. In this work, we developed the first model able to classify more than 200,000 cases of perturbations with accuracy, sensitivity, and specificity >90% both in training and validation series. The perturbations include structural changes in >50000 peptides determined in experimental assays with boundary conditions involving >500 source organisms, >50 host organisms, >10 biological process, and >30 experimental techniques. The model may be useful for the prediction of new epitopes or the optimization of known peptides towards computational vaccine design.",2014 Jan 12,"['González-Díaz, Humberto', 'Pérez-Montoto, Lázaro G.', 'Ubeira, Florencio M.']",J Immunol Res,,,True
900f9612d2b06b3e32f4d460305a282d259f370d,PMC,Comparison of DNA-Hydrolyzing Antibodies from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis,http://dx.doi.org/10.1371/journal.pone.0093001,PMC3988009,24736683,CC BY,"It was found that high-affinity anti-DNA antibodies were one of the major components of the intrathecal IgG response in multiple sclerosis (MS) patients [Williamson et al., PNAS, 2001]. Recently we have shown that IgGs from the sera of MS patients are active in the hydrolysis of DNA. Here we have shown, for the first time, that average concentration of total proteins (132-fold), total IgGs (194-fold) and anti-DNA antibodies (200-fold) in the sera is significantly higher than that in the cerebrospinal fluid (CSF) of fifteen MS patients. The relative activities of total protein from sera and CSFs varied remarkably from patient to patient. It was surprising that the specific DNase activity of the total protein of CSF reparations were 198-fold higher than the serum ones. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We present first evidence showing that IgGs from CSF not only bind but efficiently hydrolyze DNA and that average specific DNase activity of homogeneous antibodies from CSF is unpredictably ∼49-fold higher than that from the sera of the same MS patients. Some possible reasons of these findings are discussed. We suggest that DNase IgGs of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and MS pathogenesis development.",2014 Apr 15,"['Parkhomenko, Taisiya A.', 'Doronin, Vasilii B.', 'Castellazzi, Massimiliano', 'Padroni, Marina', 'Pastore, Michela', 'Buneva, Valentina N.', 'Granieri, Enrico', 'Nevinsky, Georgy A.']",PLoS One,,,True
d4190432c724cc90504db6a90053c0a61057eb7c,PMC,"Detection of the Influenza A(H1N1)pdm09 Virus Carrying the K-15E, P83S and Q293H Mutations in Patients Who Have Undergone Bone Marrow Transplant",http://dx.doi.org/10.1371/journal.pone.0094822,PMC3989246,24740088,CC BY,"The 2009 pandemic influenza A(H1N1)pdm09 virus emerged and caused considerable morbidity and mortality in the third world, especially in Brazil. Although circulating strains of A(H1N1)pdm09 are A/California/04/2009-like (CA-04-like) viruses, various studies have suggested that some mutations in the viral hemagglutinin (HA) may be associated with enhanced severity and fatality. This phenomenon is particularly challenging for immunocompromised individuals, such as those who have undergone bone marrow transplant (BMT), because they are more likely to display worse clinical outcomes to influenza infection than non-immunocompromised individuals. We studied the clinical and viral aspects of post-BMT patients with confirmed A(H1N1)pdm09 diagnosis in the largest cancer hospital in Brazil. We found a viral strain with K-15E, P83S and Q293H polymorphisms in the HA, which is presumably more virulent, in these individuals. Despite that, these patients showed only mild symptoms of infection. Our findings complement the discovery of mild cases of infection with the A(H1N1)pdm09 virus with the K-15E, P83S and Q293H mutations in Brazil and oppose other studies that have linked these changes with increased disease severity. These results could be important for a better comprehension of the impact of the pandemic influenza in the context of BMT.",2014 Apr 16,"['Mesquita, Milene', 'Resende, Paola', 'Marttorelli, Andressa', 'Machado, Viviane', 'Sacramento, Carolina Q.', 'Fintelman-Rodrigues, Natalia', 'Abrantes, Juliana L.', 'Tavares, Rita', 'Schirmer, Marcelo', 'Siqueira, Marilda M.', 'Souza, Thiago Moreno L.']",PLoS One,,,True
e782e045471faad6e0a63dae1f064e345d754493,PMC,Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0095322,PMC3989284,24740153,CC BY,"Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.",2014 Apr 16,"Kikhno, Irina",PLoS One,,,True
c21d33b3490e3e6d79a368346f37459d7b400dd7,PMC,Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0095322,PMC3989284,24740153,CC BY,"Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.",2014 Apr 16,"Kikhno, Irina",PLoS One,,,False
2c6ed53ad8928f5004e26f4c8312623b6e9c8b28,PMC,Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0095322,PMC3989284,24740153,CC BY,"Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.",2014 Apr 16,"Kikhno, Irina",PLoS One,,,False
b1350b65c323c618c3b688f68922699725242ff9,PMC,Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0095322,PMC3989284,24740153,CC BY,"Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.",2014 Apr 16,"Kikhno, Irina",PLoS One,,,False
bc40cb8cb2e3be7d265ec142561efed182e9fd50,PMC,Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0095322,PMC3989284,24740153,CC BY,"Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.",2014 Apr 16,"Kikhno, Irina",PLoS One,,,False
5f5149411e4a10a325d6369bb27d3a24d0b0a801,PMC,Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0095322,PMC3989284,24740153,CC BY,"Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.",2014 Apr 16,"Kikhno, Irina",PLoS One,,,False
ab32facb1031aea8f1a2b8b5be3d3d20077388d5,PMC,Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0095322,PMC3989284,24740153,CC BY,"Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.",2014 Apr 16,"Kikhno, Irina",PLoS One,,,False
a5b5be924639d6af104435ff9f67fbefc4236fb6,PMC,Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0095322,PMC3989284,24740153,CC BY,"Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.",2014 Apr 16,"Kikhno, Irina",PLoS One,,,False
6dbe5c842f58c1846c7659a0fb4f0da62d137c73,PMC,Counteraction of the multifunctional restriction factor tetherin,http://dx.doi.org/10.3389/fmicb.2014.00163,PMC3989765,24782851,CC BY,"The interferon-inducible restriction factor tetherin (also known as CD317, BST-2 or HM1.24) has emerged as a key component of the antiviral immune response. Initially, tetherin was shown to restrict replication of various enveloped viruses by inhibiting the release of budding virions from infected cells. More recently, it has become clear that tetherin also acts as a pattern recognition receptor inducing NF-κB-dependent proinflammatory gene expression in virus infected cells. Whereas the ability to restrict virion release is highly conserved among mammalian tetherin orthologs and thus probably an ancient function of this protein, innate sensing seems to be an evolutionarily recent activity. The potent and broad antiviral activity of tetherin is reflected by the fact that many viruses evolved means to counteract this restriction factor. A continuous arms race with viruses has apparently driven the evolution of different isoforms of tetherin with different functional properties. Interestingly, tetherin has also been implicated in cellular processes that are unrelated to immunity, such as the organization of the apical actin network and membrane microdomains or stabilization of the Golgi apparatus. In this review, I summarize our current knowledge of the different functions of tetherin and describe the molecular strategies that viruses have evolved to antagonize or evade this multifunctional host restriction factor.",2014 Apr 10,"Sauter, Daniel",Front Microbiol,,,True
5534fcf5c7e7df182da3c253d2312cd5662259b8,PMC,The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication,http://dx.doi.org/10.1371/journal.ppat.1004051,PMC3990711,24743583,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.",2014 Apr 17,"['Kovalev, Nikolay', 'Nagy, Peter D.']",PLoS Pathog,,,True
479da48b0ba5eadbcf457e609adfe701fba6f27a,PMC,The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication,http://dx.doi.org/10.1371/journal.ppat.1004051,PMC3990711,24743583,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.",2014 Apr 17,"['Kovalev, Nikolay', 'Nagy, Peter D.']",PLoS Pathog,,,False
4f2cd9ec8eed6fe97d78e1893dc0801604347e00,PMC,The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication,http://dx.doi.org/10.1371/journal.ppat.1004051,PMC3990711,24743583,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.",2014 Apr 17,"['Kovalev, Nikolay', 'Nagy, Peter D.']",PLoS Pathog,,,False
f5872038f326d5b93192fb1aebd5896624506310,PMC,The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication,http://dx.doi.org/10.1371/journal.ppat.1004051,PMC3990711,24743583,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.",2014 Apr 17,"['Kovalev, Nikolay', 'Nagy, Peter D.']",PLoS Pathog,,,False
8dd5e7afcdb1235f5b6241ebe79d22fc66e61ddf,PMC,The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication,http://dx.doi.org/10.1371/journal.ppat.1004051,PMC3990711,24743583,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.",2014 Apr 17,"['Kovalev, Nikolay', 'Nagy, Peter D.']",PLoS Pathog,,,False
483953cef653fdfa80fdce8e38788f2d503e5a72,PMC,The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication,http://dx.doi.org/10.1371/journal.ppat.1004051,PMC3990711,24743583,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.",2014 Apr 17,"['Kovalev, Nikolay', 'Nagy, Peter D.']",PLoS Pathog,,,False
80e5844199de5f7719dd366b92b5b90aa9e4f81e,PMC,The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication,http://dx.doi.org/10.1371/journal.ppat.1004051,PMC3990711,24743583,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.",2014 Apr 17,"['Kovalev, Nikolay', 'Nagy, Peter D.']",PLoS Pathog,,,False
387ef042d74eed570e829ad4b9d7b721cfc9ea27,PMC,The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication,http://dx.doi.org/10.1371/journal.ppat.1004051,PMC3990711,24743583,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.",2014 Apr 17,"['Kovalev, Nikolay', 'Nagy, Peter D.']",PLoS Pathog,,,False
a92044661e4999b7f34275c0bf742cf6e03955b5,PMC,Deficient IFN Signaling by Myeloid Cells Leads to MAVS-Dependent Virus-Induced Sepsis,http://dx.doi.org/10.1371/journal.ppat.1004086,PMC3990718,24743949,CC BY,"The type I interferon (IFN) signaling response limits infection of many RNA and DNA viruses. To define key cell types that require type I IFN signaling to orchestrate immunity against West Nile virus (WNV), we infected mice with conditional deletions of the type I IFN receptor (IFNAR) gene. Deletion of the Ifnar gene in subsets of myeloid cells resulted in uncontrolled WNV replication, vasoactive cytokine production, sepsis, organ damage, and death that were remarkably similar to infection of Ifnar (−/−) mice completely lacking type I IFN signaling. In Mavs(−/−)×Ifnar(−/−) myeloid cells and mice lacking both Ifnar and the RIG-I-like receptor adaptor gene Mavs, cytokine production was muted despite high levels of WNV infection. Thus, in myeloid cells, viral infection triggers signaling through MAVS to induce proinflammatory cytokines that can result in sepsis and organ damage. Viral pathogenesis was caused in part by massive complement activation, as liver damage was minimized in animals lacking complement components C3 or factor B or treated with neutralizing anti-C5 antibodies. Disease in Ifnar (−/−) and CD11c Cre(+) Ifnar (f/f) mice also was facilitated by the proinflammatory cytokine TNF-α, as blocking antibodies diminished complement activation and prolonged survival without altering viral burden. Collectively, our findings establish the dominant role of type I IFN signaling in myeloid cells in restricting virus infection and controlling pathological inflammation and tissue injury.",2014 Apr 17,"['Pinto, Amelia K.', 'Ramos, Hilario J.', 'Wu, Xiaobo', 'Aggarwal, Shilpa', 'Shrestha, Bimmi', 'Gorman, Matthew', 'Kim, Kristin Y.', 'Suthar, Mehul S.', 'Atkinson, John P.', 'Gale Jr, Michael', 'Diamond, Michael S.']",PLoS Pathog,,,True
ad4fdcc457c573beda847d0999a02d9e1c9fb151,PMC,Deficient IFN Signaling by Myeloid Cells Leads to MAVS-Dependent Virus-Induced Sepsis,http://dx.doi.org/10.1371/journal.ppat.1004086,PMC3990718,24743949,CC BY,"The type I interferon (IFN) signaling response limits infection of many RNA and DNA viruses. To define key cell types that require type I IFN signaling to orchestrate immunity against West Nile virus (WNV), we infected mice with conditional deletions of the type I IFN receptor (IFNAR) gene. Deletion of the Ifnar gene in subsets of myeloid cells resulted in uncontrolled WNV replication, vasoactive cytokine production, sepsis, organ damage, and death that were remarkably similar to infection of Ifnar (−/−) mice completely lacking type I IFN signaling. In Mavs(−/−)×Ifnar(−/−) myeloid cells and mice lacking both Ifnar and the RIG-I-like receptor adaptor gene Mavs, cytokine production was muted despite high levels of WNV infection. Thus, in myeloid cells, viral infection triggers signaling through MAVS to induce proinflammatory cytokines that can result in sepsis and organ damage. Viral pathogenesis was caused in part by massive complement activation, as liver damage was minimized in animals lacking complement components C3 or factor B or treated with neutralizing anti-C5 antibodies. Disease in Ifnar (−/−) and CD11c Cre(+) Ifnar (f/f) mice also was facilitated by the proinflammatory cytokine TNF-α, as blocking antibodies diminished complement activation and prolonged survival without altering viral burden. Collectively, our findings establish the dominant role of type I IFN signaling in myeloid cells in restricting virus infection and controlling pathological inflammation and tissue injury.",2014 Apr 17,"['Pinto, Amelia K.', 'Ramos, Hilario J.', 'Wu, Xiaobo', 'Aggarwal, Shilpa', 'Shrestha, Bimmi', 'Gorman, Matthew', 'Kim, Kristin Y.', 'Suthar, Mehul S.', 'Atkinson, John P.', 'Gale Jr, Michael', 'Diamond, Michael S.']",PLoS Pathog,,,False
0c361ff7d4302f316571dd1b313c4b841c15c66a,PMC,Deficient IFN Signaling by Myeloid Cells Leads to MAVS-Dependent Virus-Induced Sepsis,http://dx.doi.org/10.1371/journal.ppat.1004086,PMC3990718,24743949,CC BY,"The type I interferon (IFN) signaling response limits infection of many RNA and DNA viruses. To define key cell types that require type I IFN signaling to orchestrate immunity against West Nile virus (WNV), we infected mice with conditional deletions of the type I IFN receptor (IFNAR) gene. Deletion of the Ifnar gene in subsets of myeloid cells resulted in uncontrolled WNV replication, vasoactive cytokine production, sepsis, organ damage, and death that were remarkably similar to infection of Ifnar (−/−) mice completely lacking type I IFN signaling. In Mavs(−/−)×Ifnar(−/−) myeloid cells and mice lacking both Ifnar and the RIG-I-like receptor adaptor gene Mavs, cytokine production was muted despite high levels of WNV infection. Thus, in myeloid cells, viral infection triggers signaling through MAVS to induce proinflammatory cytokines that can result in sepsis and organ damage. Viral pathogenesis was caused in part by massive complement activation, as liver damage was minimized in animals lacking complement components C3 or factor B or treated with neutralizing anti-C5 antibodies. Disease in Ifnar (−/−) and CD11c Cre(+) Ifnar (f/f) mice also was facilitated by the proinflammatory cytokine TNF-α, as blocking antibodies diminished complement activation and prolonged survival without altering viral burden. Collectively, our findings establish the dominant role of type I IFN signaling in myeloid cells in restricting virus infection and controlling pathological inflammation and tissue injury.",2014 Apr 17,"['Pinto, Amelia K.', 'Ramos, Hilario J.', 'Wu, Xiaobo', 'Aggarwal, Shilpa', 'Shrestha, Bimmi', 'Gorman, Matthew', 'Kim, Kristin Y.', 'Suthar, Mehul S.', 'Atkinson, John P.', 'Gale Jr, Michael', 'Diamond, Michael S.']",PLoS Pathog,,,False
a69e74d1f10d384fc703f38564490fe994bc7bf2,PMC,Deficient IFN Signaling by Myeloid Cells Leads to MAVS-Dependent Virus-Induced Sepsis,http://dx.doi.org/10.1371/journal.ppat.1004086,PMC3990718,24743949,CC BY,"The type I interferon (IFN) signaling response limits infection of many RNA and DNA viruses. To define key cell types that require type I IFN signaling to orchestrate immunity against West Nile virus (WNV), we infected mice with conditional deletions of the type I IFN receptor (IFNAR) gene. Deletion of the Ifnar gene in subsets of myeloid cells resulted in uncontrolled WNV replication, vasoactive cytokine production, sepsis, organ damage, and death that were remarkably similar to infection of Ifnar (−/−) mice completely lacking type I IFN signaling. In Mavs(−/−)×Ifnar(−/−) myeloid cells and mice lacking both Ifnar and the RIG-I-like receptor adaptor gene Mavs, cytokine production was muted despite high levels of WNV infection. Thus, in myeloid cells, viral infection triggers signaling through MAVS to induce proinflammatory cytokines that can result in sepsis and organ damage. Viral pathogenesis was caused in part by massive complement activation, as liver damage was minimized in animals lacking complement components C3 or factor B or treated with neutralizing anti-C5 antibodies. Disease in Ifnar (−/−) and CD11c Cre(+) Ifnar (f/f) mice also was facilitated by the proinflammatory cytokine TNF-α, as blocking antibodies diminished complement activation and prolonged survival without altering viral burden. Collectively, our findings establish the dominant role of type I IFN signaling in myeloid cells in restricting virus infection and controlling pathological inflammation and tissue injury.",2014 Apr 17,"['Pinto, Amelia K.', 'Ramos, Hilario J.', 'Wu, Xiaobo', 'Aggarwal, Shilpa', 'Shrestha, Bimmi', 'Gorman, Matthew', 'Kim, Kristin Y.', 'Suthar, Mehul S.', 'Atkinson, John P.', 'Gale Jr, Michael', 'Diamond, Michael S.']",PLoS Pathog,,,False
423a10412afb0aef150b143711b96b0dae789ba4,PMC,Deficient IFN Signaling by Myeloid Cells Leads to MAVS-Dependent Virus-Induced Sepsis,http://dx.doi.org/10.1371/journal.ppat.1004086,PMC3990718,24743949,CC BY,"The type I interferon (IFN) signaling response limits infection of many RNA and DNA viruses. To define key cell types that require type I IFN signaling to orchestrate immunity against West Nile virus (WNV), we infected mice with conditional deletions of the type I IFN receptor (IFNAR) gene. Deletion of the Ifnar gene in subsets of myeloid cells resulted in uncontrolled WNV replication, vasoactive cytokine production, sepsis, organ damage, and death that were remarkably similar to infection of Ifnar (−/−) mice completely lacking type I IFN signaling. In Mavs(−/−)×Ifnar(−/−) myeloid cells and mice lacking both Ifnar and the RIG-I-like receptor adaptor gene Mavs, cytokine production was muted despite high levels of WNV infection. Thus, in myeloid cells, viral infection triggers signaling through MAVS to induce proinflammatory cytokines that can result in sepsis and organ damage. Viral pathogenesis was caused in part by massive complement activation, as liver damage was minimized in animals lacking complement components C3 or factor B or treated with neutralizing anti-C5 antibodies. Disease in Ifnar (−/−) and CD11c Cre(+) Ifnar (f/f) mice also was facilitated by the proinflammatory cytokine TNF-α, as blocking antibodies diminished complement activation and prolonged survival without altering viral burden. Collectively, our findings establish the dominant role of type I IFN signaling in myeloid cells in restricting virus infection and controlling pathological inflammation and tissue injury.",2014 Apr 17,"['Pinto, Amelia K.', 'Ramos, Hilario J.', 'Wu, Xiaobo', 'Aggarwal, Shilpa', 'Shrestha, Bimmi', 'Gorman, Matthew', 'Kim, Kristin Y.', 'Suthar, Mehul S.', 'Atkinson, John P.', 'Gale Jr, Michael', 'Diamond, Michael S.']",PLoS Pathog,,,False
5e022a5ce7ca2c5463c52d20ed1a1e63259c17a7,PMC,Complete Genome Sequence of Porcine Coronavirus HKU15 Strain IN2847 from the United States,http://dx.doi.org/10.1128/genomeA.00291-14,PMC3990748,24744332,CC BY,"Porcine coronavirus HKU15 (PorCoV HKU15) was first detected in pigs with clinical diseases in February 2014 in the United States. Here, we report the complete genome sequence of Indiana strain IN2847, which might be useful for understanding the molecular profile of PorCoV HKU15.",2014 Apr 17,"['Wang, Leyi', 'Zhang, Yan', 'Byrum, Beverly']",Genome Announc,,,True
3207d738e32216ee810dcb38fdbdf73d47eafaca,PMC,Glycyrrhizin improves p75NTR-associated sciatic nerve regeneration in a BALB/c mouse model,http://dx.doi.org/10.3892/etm.2014.1546,PMC3991491,24940400,CC BY,"Glycyrrhizin has a role in immune regulation in the central nervous system, but its impact on sciatic nerve injury had not previously been reported. In this study, a BALB/c mouse model of sciatic nerve injury was used to explore the role of glycyrrhizin in sciatic nerve repair and its underlying mechanism. Glycyrrhizin with intragastric gavage of 10 and 20 mg/kg weight per day (mid- and high-dose, respectively) inhibited p75 neurotrophin receptor (p75NTR) expression at the protein and mRNA levels versus the 5 mg/kg (low-dose) group and control (0.9% NaCl solution) at one, two, four and eight weeks following sciatic nerve injury, and simultaneously improved the action potential amplitude and motor nerve conductive velocity. Combined Marsland, Glees and Erikson’s silver stain and Luxol fast blue staining results indicated that high- and mid-dose glycyrrhizin promoted improved sciatic nerve myelination compared with the low-dose or control groups eight weeks after injury. Immunofluorescence staining demonstrated that glycyrrhizin had an inhibitory effect to a certain degree on local hypertrophic scar and inflammatory responses in the mouse model. In conclusion, glycyrrhizin can promote sciatic nerve regeneration and functional repair, in which doses of 10 and 20 mg/kg per day are more effective than lower doses, and such regeneration is associated with the downregulation of p75NTR.",2014 May 14,"['JIA, YU-XI', 'LI, JIN-RAN', 'MAO, CUI-YING', 'YIN, WEI-TIAN', 'JIANG, RI-HUA']",Exp Ther Med,,,True
aca7762f80af606fe3c6d2614096db74f1398368,PMC,Development of VHH Antibodies against Dengue Virus Type 2 NS1 and Comparison with Monoclonal Antibodies for Use in Immunological Diagnosis,http://dx.doi.org/10.1371/journal.pone.0095263,PMC3994031,24751715,CC BY,"The possibility of using variable domain heavy-chain antibodies (VHH antibodies) as diagnostic tools for dengue virus (DENV) type 2 NS1 protein was investigated and compared with the use of conventional monoclonal antibodies. After successful expression of DENV type 2 NS1 protein, the genes of VHH antibodies against NS1 protein were biopanned from a non-immune llama library by phage display. VHH antibodies were then expressed and purified from Escherichia coli. Simultaneously, monoclonal antibodies were obtained by the conventional route. Sequence analysis of the VHH antibodies revealed novel and long complementarity determining regions 3 (CDR3). Epitope mapping was performed via a phage display peptide library using purified VHH and monoclonal antibodies as targets. Interestingly, the same region of NS1, which comprises amino acids (224)HWPKPHTLW(232), was conserved for both kinds of antibodies displaying the consensus motif histidine-tryptophan-tryptophan or tryptophan-proline-tryptophan. The two types of antibodies were used to prepare rapid diagnostic kits based on immunochromatographic assay. The VHH antibody immobilized rapid diagnostic kit showed better sensitivity and specificity than the monoclonal antibody immobilized rapid diagnostic kit, which might be due to the long CDR3 regions of the VHH antibodies and their ability to bind to the pocket and cleft of the targeted antigen. This demonstrates that VHH antibodies are likely to be an option for developing point-of-care tests against DENV infection.",2014 Apr 21,"['Fatima, Aneela', 'Wang, Haiying', 'Kang, Keren', 'Xia, Liliang', 'Wang, Ying', 'Ye, Wei', 'Wang, Jufang', 'Wang, Xiaoning']",PLoS One,,,True
98bc863e44dea730a7952a8b6bc62292fe5da07a,PMC,Viral Infection Is Not Uncommon in Adult Patients with Severe Hospital-Acquired Pneumonia,http://dx.doi.org/10.1371/journal.pone.0095865,PMC3994115,24752070,CC BY,"BACKGROUND: Viral pathogens have not generally been regarded as important causes of severe hospital-acquired pneumonia (HAP), except in patients with hematologic malignancy or transplant recipients. We investigated the role and distribution of viruses in adult with severe HAP who required intensive care. METHODS: From March 2010 to February 2012, adult patients with severe HAP required admission to the intensive care unit (ICU), 28-bed medical ICU in a tertiary care hospital, were prospectively enrolled. Respiratory viruses were detected using multiplex reverse-transcription polymerase chain reaction and/or shell vial culture. RESULTS: A total of 262 patients were enrolled and 107 patients (40.8%) underwent bronchoscopic BAL for etiologic diagnosis. One hundred and fifty-six patients (59.5%) had bacterial infections and 59 patients (22.5%) had viral infections. Viruses were detected in BAL fluid specimens of 37 patients (62.7%, 37/59). The most commonly identified viruses were respiratory syncytial virus and parainfluenza virus (both 27.1%, 16/59), followed by rhinovirus (25.4%, 15/59), and influenza virus (16.9%, 10/59). Twenty-one patients (8.0%, 21/262) had bacterial-viral coinfections and Staphylococcus aureus was the most commonly coexisting bacteria (n = 10). Viral infection in non-immunocompromised patients was not uncommon (11.1%, 16/143), although it was not as frequent as that in immunocompromised patients (36.4%, 43/119). Non-immunocompromised patients were significantly older than immunocompromised patients and had significantly higher rates of underlying chronic obstructive pulmonary disease, tuberculous destroyed lung and chronic kidney disease. The 28 day mortalities of patients with bacterial infections, viral infections and bacterial-viral coinfections were not significantly different (29.5%, 35.6% and 19.0%, respectively; p = 0.321). CONCLUSIONS: Viral pathogens are not uncommon in adult patients with severe HAP who required ICU admission. Since viral pathogens may cause severe HAP and could be a potential source of viral transmission, further investigation is required to delineate the role of viral pathogens in severe HAP.",2014 Apr 21,"['Hong, Hyo-Lim', 'Hong, Sang-Bum', 'Ko, Gwang-Beom', 'Huh, Jin Won', 'Sung, Heungsup', 'Do, Kyung-Hyun', 'Kim, Sung-Han', 'Lee, Sang-Oh', 'Kim, Mi-Na', 'Jeong, Jin-Yong', 'Lim, Chae-Man', 'Kim, Yang Soo', 'Woo, Jun Hee', 'Koh, Younsuck', 'Choi, Sang-Ho']",PLoS One,,,True
66f31952c8b998f8c9de4d34c17a7c2e0d2e35fa,PMC,Activation of the PKR/eIF2α signaling cascade inhibits replication of Newcastle disease virus,http://dx.doi.org/10.1186/1743-422X-11-62,PMC3994276,24684861,CC BY,"BACKGROUND: Newcastle Disease virus (NDV) causes severe and economically significant disease in almost all birds. However, factors that affect NDV replication in host cells are poorly understood. NDV generates long double-stranded RNA (dsRNA) molecules during transcription of single-stranded genomic RNA. Protein kinase R (PKR) is activated by dsRNA. The aim of this study was to elucidate the role of PKR in NDV infection. RESULTS: NDV infection led to the activation of dsRNA-dependent PKR and phosphorylation of its substrate, translation initiation factor eIF2α, in a dose-dependent manner by either the lentogenic strain LaSota or a velogenic strain Herts/33. PKR activation coincided with the accumulation of dsRNA induced by NDV infection. PKR knockdown remarkably decreased eIF2α phosphorylation as well as IFN-β mRNA levels, leading to the augmentation of extracellular virus titer. Furthermore, siRNA knockdown or phosphorylation of eIF2α or okadaic acid treatment significantly impaired NDV replication, indicating the critical role of the PKR/eIF2α signaling cascade in NDV infection. CONCLUSION: PKR is activated by dsRNA generated by NDV infection and inhibits NDV replication by eIF2α phosphorylation. This study provides insight into NDV-host interactions for the development of candidate antiviral strategies.",2014 Mar 31,"['Zhang, Shilei', 'Sun, Yingjie', 'Chen, Hongjun', 'Dai, Yabin', 'Zhan, Yuan', 'Yu, Shengqing', 'Qiu, Xusheng', 'Tan, Lei', 'Song, Cuiping', 'Ding, Chan']",Virol J,,,True
417a6772d67e3b958d27a80ed09cabfea228d432,PMC,Impact of 2013 south Asian haze crisis: study of physical and psychological symptoms and perceived dangerousness of pollution level,http://dx.doi.org/10.1186/1471-244X-14-81,PMC3995317,24642046,CC BY,"BACKGROUND: The widespread forest fires in Indonesia in June 2013 led to widespread haze to neighbouring countries. This is the first study in the medical literature reporting the acute physical and psychological symptoms of the general population during a haze crisis. We evaluated the factors that are associated with psychological stress of haze exposure. METHODS: This study was conducted between June 21 to June 26, 2013. Participants were recruited by an online recruitment post and snowball sampling techniques. Participants were required to complete an online survey which was composed of demographics questionnaire, physical symptom checklist, perceived dangerous Pollutant Standard Index (PSI) value and views on the N-95 mask and the Impact of Event Scale-Revised (IES-R). RESULTS: A total of 298 participants returned the completed study questionnaire. The respondents reported a mean number of 4.03 physical symptoms (S.D. = 2.6). The five most common physical symptoms include mouth or throat discomfort (68.8%), nose discomfort (64.1%), eye discomfort (60.7%), headache (50.3%) and breathing difficulty (40.3%). The total IES-R score was 18.47 (S.D. = 11.69) which indicated that the study population experienced mild psychological stress but not to the extent of acute stress reaction syndrome. The perceived dangerous PSI level and number of physical symptoms were significantly associated with the mean intrusion score, mean hyper-arousal score, total mean IES-R score and total IES-R score (p < 0.05). CONCLUSIONS: Our findings suggest that a haze crisis is associated with acute physical symptoms and mild psychological stress. The number of physical symptoms and the perceived dangerous PSI values are important factors associated with psychological stress.",2014 Mar 19,"['Ho, Roger C', 'Zhang, Melvyn W', 'Ho, Cyrus S', 'Pan, Fang', 'Lu, Yanxia', 'Sharma, Vijay K']",BMC Psychiatry,,,True
a11b3479a9f0e004870ecefa643c4c311c6066cb,PMC,Fluorescence in situ hybridization investigation of potentially pathogenic bacteria involved in neonatal porcine diarrhea,http://dx.doi.org/10.1186/1746-6148-10-68,PMC3995547,24628856,CC BY,"BACKGROUND: Neonatal diarrhea is a multifactorial condition commonly present on pig farms and leads to economic losses due to increased morbidity and mortality of piglets. Immature immune system and lack of fully established microbiota at birth predispose neonatal piglets to infection with enteric pathogens. The microorganisms that for decades have been associated with enteritis and diarrhea in suckling piglets are: rotavirus A, coronavirus, enterotoxigenic Escherichia coli (ETEC), Clostridium perfringens type C, Cryptosporidium spp., Giardia spp., Cystoisospora suis and Strongyloides ransomi. However, in recent years, the pig industry has experienced an increased number of neonatal diarrhea cases in which the above mentioned pathogens are no longer detected. Potentially pathogenic bacteria have recently received focus in the research on the possible etiology of neonatal diarrhea not caused by common pathogens. The primary aim of this study was to investigate the role of E. coli, Enterococcus spp., C. perfringens and C. difficile in the pathogenesis of neonatal porcine diarrhea with no established casual agents. Fluorescence in situ hybridization with oligonucleotide probes was applied on the fixed intestinal tissue samples from 51 diarrheic and 50 non-diarrheic piglets collected from four Danish farms during outbreaks of neonatal diarrhea not caused by well-known enteric pathogens. Furthermore, an association between the presence of these bacteria and histological lesions was evaluated. RESULTS: The prevalence of fluorescence signals specific for E. coli, C. perfringens and C. difficile was similar in both groups of piglets. However, Enterococcus spp. was primarily detected in the diarrheic piglets. Furthermore, adherent bacteria were detected in 37 % diarrheic and 14 % non-diarrheic piglets. These bacteria were identified as E. coli and Enterococcus spp. and their presence in the intestinal mucosa was associated with histopathological changes. CONCLUSIONS: The results of this study showed that simultaneous colonization of the intestinal mucosa by adherent non-ETEC E. coli and Enterococcus spp. can be involved in the pathogenesis of neonatal porcine diarrhea. These bacteria should be considered in diagnosis of diarrhea in piglets, when detection of common, well-known enteric agents is unsuccessful.",2014 Mar 14,"['Jonach, Beata', 'Boye, Mette', 'Stockmarr, Anders', 'Jensen, Tim Kåre']",BMC Vet Res,,,True
93edcf98f17f9827882fbaed728fb18a8a51cc1d,PMC,Serological report of pandemic (H1N1) 2009 infection among cats in Northeastern China in 2012-02 and 2013-03,http://dx.doi.org/10.1186/1743-422X-11-49,PMC3995557,24624924,CC BY,"BACKGROUND: Influenza A virus has a wide range of hosts. It has not only infected human, but also been reported interspecies transmission from humans to other animals, such as pigs, poultry, dogs and cats. However, prevalence of A (H1N1) pdm09 influenza virus infections in cats in northeastern China is unknown. Therefore, the prevalence of A (H1N1) pdm09 influenza virus infections was performed among cats in northeastern China in this study. FINDINGS: Of all samples in this study, the overall seroprevalence of pandemic (H1N1) 2009 infection in cats was 21% (240/1140). It also showed a higher prevalence rate of pandemic(H1N1) 2009 infection in pet cats (30.6%) than roaming cats (11%) based on NT. In addition, the results also showed a trend of difference in term of species of cats and it was statistically significant. CONCLUSIONS: This is the first survey on the seroprevalence of pandemic (H1N1) 2009 infection among cats in northeastern China. This study has observed a relatively high seroprevalence of pandemic (H1N1) 2009 among different cat populations in northeastern China, similar seroprevalence studies should be conducted elsewhere.",2014 Mar 14,"['Zhao, Fu-Rong', 'Liu, Chun-Guo', 'Yin, Xin', 'Zhou, Dong-Hui', 'Wei, Ping', 'Chang, Hui-Yun']",Virol J,,,True
018b618ea132d47ffb43b003a6c78cb9eeadc017,PMC,Unique Epitopes Recognized by Antibodies Induced in Chikungunya Virus-Infected Non-Human Primates: Implications for the Study of Immunopathology and Vaccine Development,http://dx.doi.org/10.1371/journal.pone.0095647,PMC3995782,24755730,CC BY,"Chikungunya virus (CHIKV) is an Alphavirus that causes chronic and incapacitating arthralgia in humans. Although patient cohort studies have shown the production of CHIKV specific antibodies, the fine specificity of the antibody response against CHIKV is not completely defined. The macaque model of CHIKV infection was established due to limitations of clinical specimens. More importantly, its close relation to humans will allow the study of chronic infection and further identify important CHIKV targets. In this study, serum samples from CHIKV-infected macaques collected at different time-points post infection were used to characterize the antibody production pattern and kinetics. Results revealed that anti-CHIKV antibodies were neutralizing and the E2 glycoprotein, Capsid, nsP1, nsP3 and nsP4 proteins were targets of the anti-CHIKV antibody response in macaques. Furthermore, linear B-cell epitopes recognized by these anti-CHIKV antibodies were identified, and mapped to their structural localization. This characterizes the specificity of anti-CHIKV antibody response in macaques and further demonstrates the importance of the different regions in CHIKV-encoded proteins in the adaptive immune response. Information from this study provides critical knowledge that will aid in the understanding of CHIKV infection and immunity, vaccine design, and pre-clinical efficacy studies.",2014 Apr 22,"['Kam, Yiu-Wing', 'Lee, Wendy W. L.', 'Simarmata, Diane', 'Le Grand, Roger', 'Tolou, Hugues', 'Merits, Andres', 'Roques, Pierre', 'Ng, Lisa F. P.']",PLoS One,,,True
08e013666eb4c5dde725c49c2f2b701f05572a0c,PMC,Unique Epitopes Recognized by Antibodies Induced in Chikungunya Virus-Infected Non-Human Primates: Implications for the Study of Immunopathology and Vaccine Development,http://dx.doi.org/10.1371/journal.pone.0095647,PMC3995782,24755730,CC BY,"Chikungunya virus (CHIKV) is an Alphavirus that causes chronic and incapacitating arthralgia in humans. Although patient cohort studies have shown the production of CHIKV specific antibodies, the fine specificity of the antibody response against CHIKV is not completely defined. The macaque model of CHIKV infection was established due to limitations of clinical specimens. More importantly, its close relation to humans will allow the study of chronic infection and further identify important CHIKV targets. In this study, serum samples from CHIKV-infected macaques collected at different time-points post infection were used to characterize the antibody production pattern and kinetics. Results revealed that anti-CHIKV antibodies were neutralizing and the E2 glycoprotein, Capsid, nsP1, nsP3 and nsP4 proteins were targets of the anti-CHIKV antibody response in macaques. Furthermore, linear B-cell epitopes recognized by these anti-CHIKV antibodies were identified, and mapped to their structural localization. This characterizes the specificity of anti-CHIKV antibody response in macaques and further demonstrates the importance of the different regions in CHIKV-encoded proteins in the adaptive immune response. Information from this study provides critical knowledge that will aid in the understanding of CHIKV infection and immunity, vaccine design, and pre-clinical efficacy studies.",2014 Apr 22,"['Kam, Yiu-Wing', 'Lee, Wendy W. L.', 'Simarmata, Diane', 'Le Grand, Roger', 'Tolou, Hugues', 'Merits, Andres', 'Roques, Pierre', 'Ng, Lisa F. P.']",PLoS One,,,False
491f229f1a4bc9fb8f4c85097040666e5ad1c455,PMC,Determining the dynamics of influenza transmission by age,http://dx.doi.org/10.1186/1742-7622-11-4,PMC3997935,24656239,CC BY,"BACKGROUND: It is widely accepted that influenza transmission dynamics vary by age; however methods to quantify the reproductive number by age group are limited. We introduce a simple method to estimate the reproductive number by modifying the method originally proposed by Wallinga and Teunis and using existing information on contact patterns between age groups. We additionally perform a sensitivity analysis to determine the potential impact of differential healthcare seeking patterns by age. We illustrate this method using data from the 2009 H1N1 Influenza pandemic in Gauteng Province, South Africa. RESULTS: Our results are consistent with others in showing decreased transmission with age. We show that results can change markedly when we make the account for differential healthcare seeking behaviors by age. CONCLUSIONS: We show substantial heterogeneity in transmission by age group during the Influenza A H1N1 pandemic in South Africa. This information can greatly assist in targeting interventions and implementing social distancing measures.",2014 Mar 21,"['White, Laura F', 'Archer, Brett', 'Pagano, Marcello']",Emerg Themes Epidemiol,,,True
90394841ad2cbaec78bf51646d5ca1ae26fadba6,PMC,Bayesian Analysis for Inference of an Emerging Epidemic: Citrus Canker in Urban Landscapes,http://dx.doi.org/10.1371/journal.pcbi.1003587,PMC3998883,24762851,CC0,"Outbreaks of infectious diseases require a rapid response from policy makers. The choice of an adequate level of response relies upon available knowledge of the spatial and temporal parameters governing pathogen spread, affecting, amongst others, the predicted severity of the epidemic. Yet, when a new pathogen is introduced into an alien environment, such information is often lacking or of no use, and epidemiological parameters must be estimated from the first observations of the epidemic. This poses a challenge to epidemiologists: how quickly can the parameters of an emerging disease be estimated? How soon can the future progress of the epidemic be reliably predicted? We investigate these issues using a unique, spatially and temporally resolved dataset for the invasion of a plant disease, Asiatic citrus canker in urban Miami. We use epidemiological models, Bayesian Markov-chain Monte Carlo, and advanced spatial statistical methods to analyse rates and extent of spread of the disease. A rich and complex epidemic behaviour is revealed. The spatial scale of spread is approximately constant over time and can be estimated rapidly with great precision (although the evidence for long-range transmission is inconclusive). In contrast, the rate of infection is characterised by strong monthly fluctuations that we associate with extreme weather events. Uninformed predictions from the early stages of the epidemic, assuming complete ignorance of the future environmental drivers, fail because of the unpredictable variability of the infection rate. Conversely, predictions improve dramatically if we assume prior knowledge of either the main environmental trend, or the main environmental events. A contrast emerges between the high detail attained by modelling in the spatiotemporal description of the epidemic and the bottleneck imposed on epidemic prediction by the limits of meteorological predictability. We argue that identifying such bottlenecks will be a fundamental step in future modelling of weather-driven epidemics.",2014 Apr 24,"['Neri, Franco M.', 'Cook, Alex R.', 'Gibson, Gavin J.', 'Gottwald, Tim R.', 'Gilligan, Christopher A.']",PLoS Comput Biol,,,True
d7454f33ce536b8ede6b9540b21f09c407a5e708,PMC,Bayesian Analysis for Inference of an Emerging Epidemic: Citrus Canker in Urban Landscapes,http://dx.doi.org/10.1371/journal.pcbi.1003587,PMC3998883,24762851,CC0,"Outbreaks of infectious diseases require a rapid response from policy makers. The choice of an adequate level of response relies upon available knowledge of the spatial and temporal parameters governing pathogen spread, affecting, amongst others, the predicted severity of the epidemic. Yet, when a new pathogen is introduced into an alien environment, such information is often lacking or of no use, and epidemiological parameters must be estimated from the first observations of the epidemic. This poses a challenge to epidemiologists: how quickly can the parameters of an emerging disease be estimated? How soon can the future progress of the epidemic be reliably predicted? We investigate these issues using a unique, spatially and temporally resolved dataset for the invasion of a plant disease, Asiatic citrus canker in urban Miami. We use epidemiological models, Bayesian Markov-chain Monte Carlo, and advanced spatial statistical methods to analyse rates and extent of spread of the disease. A rich and complex epidemic behaviour is revealed. The spatial scale of spread is approximately constant over time and can be estimated rapidly with great precision (although the evidence for long-range transmission is inconclusive). In contrast, the rate of infection is characterised by strong monthly fluctuations that we associate with extreme weather events. Uninformed predictions from the early stages of the epidemic, assuming complete ignorance of the future environmental drivers, fail because of the unpredictable variability of the infection rate. Conversely, predictions improve dramatically if we assume prior knowledge of either the main environmental trend, or the main environmental events. A contrast emerges between the high detail attained by modelling in the spatiotemporal description of the epidemic and the bottleneck imposed on epidemic prediction by the limits of meteorological predictability. We argue that identifying such bottlenecks will be a fundamental step in future modelling of weather-driven epidemics.",2014 Apr 24,"['Neri, Franco M.', 'Cook, Alex R.', 'Gibson, Gavin J.', 'Gottwald, Tim R.', 'Gilligan, Christopher A.']",PLoS Comput Biol,,,False
03e779f9defa0b9cb6a9943947e41b9c1532e3d3,PMC,Bayesian Analysis for Inference of an Emerging Epidemic: Citrus Canker in Urban Landscapes,http://dx.doi.org/10.1371/journal.pcbi.1003587,PMC3998883,24762851,CC0,"Outbreaks of infectious diseases require a rapid response from policy makers. The choice of an adequate level of response relies upon available knowledge of the spatial and temporal parameters governing pathogen spread, affecting, amongst others, the predicted severity of the epidemic. Yet, when a new pathogen is introduced into an alien environment, such information is often lacking or of no use, and epidemiological parameters must be estimated from the first observations of the epidemic. This poses a challenge to epidemiologists: how quickly can the parameters of an emerging disease be estimated? How soon can the future progress of the epidemic be reliably predicted? We investigate these issues using a unique, spatially and temporally resolved dataset for the invasion of a plant disease, Asiatic citrus canker in urban Miami. We use epidemiological models, Bayesian Markov-chain Monte Carlo, and advanced spatial statistical methods to analyse rates and extent of spread of the disease. A rich and complex epidemic behaviour is revealed. The spatial scale of spread is approximately constant over time and can be estimated rapidly with great precision (although the evidence for long-range transmission is inconclusive). In contrast, the rate of infection is characterised by strong monthly fluctuations that we associate with extreme weather events. Uninformed predictions from the early stages of the epidemic, assuming complete ignorance of the future environmental drivers, fail because of the unpredictable variability of the infection rate. Conversely, predictions improve dramatically if we assume prior knowledge of either the main environmental trend, or the main environmental events. A contrast emerges between the high detail attained by modelling in the spatiotemporal description of the epidemic and the bottleneck imposed on epidemic prediction by the limits of meteorological predictability. We argue that identifying such bottlenecks will be a fundamental step in future modelling of weather-driven epidemics.",2014 Apr 24,"['Neri, Franco M.', 'Cook, Alex R.', 'Gibson, Gavin J.', 'Gottwald, Tim R.', 'Gilligan, Christopher A.']",PLoS Comput Biol,,,True
e2b354fb613a71ab7f449318fe0d8c20d535e9b1,PMC,The effect of New Neonatal Porcine Diarrhoea Syndrome (NNPDS) on average daily gain and mortality in 4 Danish pig herds,http://dx.doi.org/10.1186/1746-6148-10-90,PMC3999350,24755093,CC BY,"BACKGROUND: The study evaluated the effect of New Neonatal Porcine Diarrhoea Syndrome (NNPDS) on average daily gain (ADG) and mortality and described the clinical manifestations in four herds suffering from the syndrome. NNPDS is a diarrhoeic syndrome affecting piglets within the first week of life, which is not caused by enterotoxigenic Escherichia coli (ETEC), Clostridium perfringens (C. perfringens) type A/C, Clostridium difficile (C. difficile), rotavirus A, coronavirus, Cystoisospora suis, Strongyloides ransomi, Giardia spp or Cryptosporidium spp. RESULTS: Piglets were estimated to have a negative ADG of 9 and 14 g when diarrhoeic for 1 day and >1 day respectively. However, if only diarrhoeic on the day of birth, no negative effect on ADG was seen. Piglets originating from severely affected litters were estimated to have a reduced ADG of 38 g. The study did not show an overall effect of diarrhoea on mortality, but herd of origin, sow parity, birth weight, and gender were significantly associated with mortality. In one of the herds, approximately 25% of the diarrhoeic piglets vs. 6% of the non-diarrhoeic piglets died, and 74% of necropsied piglets were diagnosed with enteritis. These findings indicate that the high mortality seen in this herd was due to diarrhoea. CONCLUSIONS: NNPDS negatively affected ADG in piglets, and even piglets that were diarrhoeic for one day only experienced a reduction in ADG. However, the study showed that diarrhoea restricted to the day of birth did not affect ADG and suggested this phenomenon to be unrelated to the syndrome. Since the diarrhoeal status of the litter had important effects on ADG, future research on NNPDS probably ought to focus on piglets from severely affected litters. The study showed important dissimilarities in the course of diarrhoea between the herds, and one herd was considerably more affected than the others. Within this herd, NNPDS seemed to be associated with a higher mortality, whereas in general the study did not show lethal effects of NNPDS.",2014 Apr 22,"['Kongsted, Hanne', 'Stege, Helle', 'Toft, Nils', 'Nielsen, Jens P']",BMC Vet Res,,,True
e608f2a6b99e0e74c16aa9085128690e20b59ea0,PMC,Severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses,http://dx.doi.org/10.1186/1742-4933-11-4,PMC3999990,24642138,CC BY,"BACKGROUND: Many respiratory viruses disproportionately impact the elderly. Likewise, advanced age correlated with more adverse disease outcomes following severe acute respiratory syndrome coronavirus (SARS-CoV) infection in humans. We used an aged African green monkey SARS-CoV infection model to better understand age-related mechanisms of increased susceptibility to viral respiratory infections. Nonhuman primates are critical translational models for such research given their similarities to humans in immune-ageing as well as lung structure. RESULTS: Significant age- and infection-dependent differences were observed in both systemic and mucosal immune compartments. Peripheral lymphocytes, specifically CD8 T and B cells were significantly lower in aged monkeys pre- and post- SARS-CoV infection, while neutrophil and monocyte numbers were not impacted by age or infection status. Serum proinflammatory cytokines were similar in both age groups, whereas significantly lower levels of IL-1beta, IL-18, IL-6, IL-12 and IL-15 were detected in the lungs of SARS-CoV-infected aged monkeys at either 5 or 10 days post infection. Total lung leukocyte numbers and relative frequency of CD8 T cells, B cells, macrophages and dendritic cells were greatly reduced in the aged host during SARS-CoV infection, despite high levels of chemoattractants for many of these cells in the aged lung. Dendritic cells and monocytes/macrophages showed age-dependent differences in activation and chemokine receptor profiles, while the CD8 T cell and B cell responses were significantly reduced in the aged host. In examination of viral titers, significantly higher levels of SARS-CoV were detected in the nasal swabs early, at day 1 post infection, in aged as compared to juvenile monkeys, but virus levels were only slightly higher in aged animals by day 3. Although there was a trend of higher titers in respiratory tissues at day 5 post infection, this did not reach statistical significance and virus was cleared from all animals by day 10, regardless of age. CONCLUSIONS: This study provides unique insight into how several parameters of the systemic and mucosal immune response to SARS-CoV infection are significantly modulated by age. These immune differences may contribute to deficient immune function and the observed trend of higher SARS-CoV replication in aged nonhuman primates.",2014 Mar 19,"['Clay, Candice C', 'Donart, Nathan', 'Fomukong, Ndingsa', 'Knight, Jennifer B', 'Overheim, Katie', 'Tipper, Jennifer', 'Van Westrienen, Jesse', 'Hahn, Fletcher', 'Harrod, Kevin S']",Immun Ageing,,,True
b7ff247b83afad127e3d971006647d12ce097d56,PMC,Improving the Diagnosis of Bloodstream Infections: PCR Coupled with Mass Spectrometry,http://dx.doi.org/10.1155/2014/501214,PMC4000954,24818144,CC BY,"The reference method for the diagnosis of bloodstream infections is blood culture followed by biochemical identification and antibiotic susceptibility testing of the isolated pathogen. This process requires 48 to 72 hours. The rapid administration of the most appropriate antimicrobial treatment is crucial for the survival of septic patients; therefore, a rapid method that enables diagnosis directly from analysis of a blood sample without culture is needed. A recently developed platform that couples broad-range PCR amplification of pathogen DNA with electrospray ionization mass spectrometry (PCR/ESI-MS) has the ability to identify virtually any microorganism from direct clinical specimens. To date, two clinical evaluations of the PCR/ESI-MS technology for the diagnosis of bloodstream infections from whole blood have been published. Here we discuss them and describe recent improvements that result in an enhanced sensitivity. Other commercially available assays for the molecular diagnosis of bloodstream infections from whole blood are also reviewed. The use of highly sensitive molecular diagnostic methods in combination with conventional procedures could substantially improve the management of septic patients.",2014 Apr 9,"['Jordana-Lluch, Elena', 'Giménez, Montserrat', 'Quesada, M. Dolores', 'Ausina, Vicente', 'Martró, Elisa']",Biomed Res Int,,,True
28564e89afd6423e291c68867dd52654258b29f8,PMC,How integration of global omics-data could help preparing for pandemics – a scent of influenza,http://dx.doi.org/10.3389/fgene.2014.00080,PMC4000993,24795745,CC BY,"Pandemics caused by novel emerging or re-emerging infectious diseases could lead to high mortality and morbidity world-wide when left uncontrolled. In this perspective, we evaluate the possibility of integration of global omics-data in order to timely prepare for pandemics. Such an approach requires two major innovations. First, data that is obtained should be shared with the global community instantly. The strength of rapid integration of simple signals is exemplified by Google’s(TM) Flu Trend, which could predict the incidence of influenza-like illness based on online search engine queries. Second, omics technologies need to be fast and high-throughput. We postulate that analysis of the exhaled breath would be a simple, rapid and non-invasive alternative. Breath contains hundreds of volatile organic compounds that are altered by infection and inflammation. The molecular fingerprint of breath (breathprint) can be obtained using an electronic nose, which relies on sensor technology. These breathprints can be stored in an online database (a “breathcloud”) and coupled to clinical data. Comparison of the breathprint of a suspected subject to the breathcloud allows for a rapid decision on the presence or absence of a pathogen.",2014 Apr 22,"['Bos, Lieuwe D. J.', 'de Jong, Menno D.', 'Sterk, Peter J.', 'Schultz, Marcus J.']",Front Genet,,,True
1f7f414d82475a8c5b2272163e6f31b474904486,PMC,Emerging gene editing strategies for Duchenne muscular dystrophy targeting stem cells,http://dx.doi.org/10.3389/fphys.2014.00148,PMC4001063,24795643,CC BY,"The progressive loss of muscle mass characteristic of many muscular dystrophies impairs the efficacy of most of the gene and molecular therapies currently being pursued for the treatment of those disorders. It is becoming increasingly evident that a therapeutic application, to be effective, needs to target not only mature myofibers, but also muscle progenitors cells or muscle stem cells able to form new muscle tissue and to restore myofibers lost as the result of the diseases or during normal homeostasis so as to guarantee effective and lost lasting effects. Correction of the genetic defect using oligodeoxynucleotides (ODNs) or engineered nucleases holds great potential for the treatment of many of the musculoskeletal disorders. The encouraging results obtained by studying in vitro systems and model organisms have set the groundwork for what is likely to become an emerging field in the area of molecular and regenerative medicine. Furthermore, the ability to isolate and expand from patients various types of muscle progenitor cells capable of committing to the myogenic lineage provides the opportunity to establish cell lines that can be used for transplantation following ex vivo manipulation and expansion. The purpose of this article is to provide a perspective on approaches aimed at correcting the genetic defect using gene editing strategies and currently under development for the treatment of Duchenne muscular dystrophy (DMD), the most sever of the neuromuscular disorders. Emphasis will be placed on describing the potential of using the patient own stem cell as source of transplantation and the challenges that gene editing technologies face in the field of regenerative biology.",2014 Apr 21,"Bertoni, Carmen",Front Physiol,,,True
8c433501a618d6a3f93463393f4ce58007abec95,PMC,Malaria vaccines: high-throughput tools for antigens discovery with potential for their development,,PMC4002024,24892459,CC BY,"Malaria is a disease induced by parasites of the Plasmodium genus, which are transmitted by Anopheles mosquitoes and represents a great socio-economic burden Worldwide. Plasmodium vivax is the second species of malaria Worldwide, but it is the most prevalent in Latin America and other regions of the planet. It is currently considered that vaccines represent a cost-effective strategy for controlling transmissible diseases and could complement other malaria control measures; however, the chemical and immunological complexity of the parasite has hindered development of effective vaccines. Recent availability of several genomes of Plasmodium species, as well as bioinformatic tools are allowing the selection of large numbers of proteins and analysis of their immune potential. Herein, we review recently developed strategies for discovery of novel antigens with potential for malaria vaccine development.",,"['Céspedes, Nora', 'Vallejo, Andrés', 'Arévalo-Herrera, Myriam', 'Herrera, Sócrates']",Colomb Med (Cali).; 44(2):121-128,,,True
8eb469fc4a148699ffdf0969e3ea75048412472d,PMC,The YXXΦ motif within the severe acute respiratory syndrome coronavirus (SARS-CoV) 3a protein is crucial for its intracellular transport,http://dx.doi.org/10.1186/1743-422X-11-75,PMC4004515,24762043,CC BY,"BACKGROUND: The SARS coronavirus (SARS-CoV) 3a protein functions as an ion channel, induces apoptosis and is important for viral pathogenesis. It is expressed on the cell surface and contains a tyrosine-based sorting motif and a di-acidic motif, which may be crucial for its intracellular trafficking. However the role of these motifs is not fully understood in the case of 3a protein. METHODS: The subcellular distribution of the 3a protein was studied by immunofluorescence staining of cells transfected with wild type and mutant constructs along with markers for different intracellular compartments. Semi-quantitative RT-PCR was performed to estimate the mRNA where as western blotting was carried out to detect protein levels of wild type and mutant 3a proteins. In vitro transcription- translation was performed to estimate cell free protein synthesis. RESULTS: While the wild type 3a protein is efficiently transported to the plasma membrane, the protein with mutations in the tyrosine and valine residues within the YXXV motif (ΔYXXΦ) accumulated in the Golgi compartment. However the 3a protein with mutations within the EXD di-acidic motif (ΔEXD) showed an intracellular distribution similar to the wild type protein. Increased retention of the ΔYXXΦ protein in the Golgi compartment also increased its association with lipid droplets. The ΔYXXΦ protein also expressed at significantly lower levels compared to the wild type 3a protein, which was reversed with Brefeldin A and Aprotinin. CONCLUSIONS: The data suggest that the YXXΦ motif of the SARS-CoV 3a protein is necessary for Golgi to plasma membrane transport, in the absence of which the protein is targeted to lysosomal degradation compartment via lipid droplets.",2014 Apr 24,"['Minakshi, Rinki', 'Padhan, Kartika']",Virol J,,,True
1f2bbc79b56c51c0ae26ced2d7d8ccf10360fa72,PMC,Ribonuclease L and metal-ion–independent endoribonuclease cleavage sites in host and viral RNAs,http://dx.doi.org/10.1093/nar/gku118,PMC4005677,24500209,CC BY,"Ribonuclease L (RNase L) is a metal-ion–independent endoribonuclease associated with antiviral and antibacterial defense, cancer and lifespan. Despite the biological significance of RNase L, the RNAs cleaved by this enzyme are poorly defined. In this study, we used deep sequencing methods to reveal the frequency and location of RNase L cleavage sites within host and viral RNAs. To make cDNA libraries, we exploited the 2′, 3′-cyclic phosphate at the end of RNA fragments produced by RNase L and other metal-ion–independent endoribonucleases. We optimized and validated 2′, 3′-cyclic phosphate cDNA synthesis and Illumina sequencing methods using viral RNAs cleaved with purified RNase L, viral RNAs cleaved with purified RNase A and RNA from uninfected and poliovirus-infected HeLa cells. Using these methods, we identified (i) discrete regions of hepatitis C virus and poliovirus RNA genomes that were profoundly susceptible to RNase L and other single-strand specific endoribonucleases, (ii) RNase L-dependent and RNase L-independent cleavage sites within ribosomal RNAs (rRNAs) and (iii) 2′, 3′-cyclic phosphates at the ends of 5S rRNA and U6 snRNA. Monitoring the frequency and location of metal-ion–independent endoribonuclease cleavage sites within host and viral RNAs reveals, in part, how these enzymes contribute to health and disease.",2014 Apr 5,"['Cooper, Daphne A.', 'Jha, Babal K.', 'Silverman, Robert H.', 'Hesselberth, Jay R.', 'Barton, David J.']",Nucleic Acids Res,,,True
ae0b9375dd56b6338cb63a3b5857e4125f5edf41,PMC,Ribonuclease L and metal-ion–independent endoribonuclease cleavage sites in host and viral RNAs,http://dx.doi.org/10.1093/nar/gku118,PMC4005677,24500209,CC BY,"Ribonuclease L (RNase L) is a metal-ion–independent endoribonuclease associated with antiviral and antibacterial defense, cancer and lifespan. Despite the biological significance of RNase L, the RNAs cleaved by this enzyme are poorly defined. In this study, we used deep sequencing methods to reveal the frequency and location of RNase L cleavage sites within host and viral RNAs. To make cDNA libraries, we exploited the 2′, 3′-cyclic phosphate at the end of RNA fragments produced by RNase L and other metal-ion–independent endoribonucleases. We optimized and validated 2′, 3′-cyclic phosphate cDNA synthesis and Illumina sequencing methods using viral RNAs cleaved with purified RNase L, viral RNAs cleaved with purified RNase A and RNA from uninfected and poliovirus-infected HeLa cells. Using these methods, we identified (i) discrete regions of hepatitis C virus and poliovirus RNA genomes that were profoundly susceptible to RNase L and other single-strand specific endoribonucleases, (ii) RNase L-dependent and RNase L-independent cleavage sites within ribosomal RNAs (rRNAs) and (iii) 2′, 3′-cyclic phosphates at the ends of 5S rRNA and U6 snRNA. Monitoring the frequency and location of metal-ion–independent endoribonuclease cleavage sites within host and viral RNAs reveals, in part, how these enzymes contribute to health and disease.",2014 Apr 5,"['Cooper, Daphne A.', 'Jha, Babal K.', 'Silverman, Robert H.', 'Hesselberth, Jay R.', 'Barton, David J.']",Nucleic Acids Res,,,True
31a744d5cdf4b8901ea26a847bbc3cc76d6e02d7,PMC,"Molecular and serological surveillance of canine enteric viruses in stray dogs from Vila do Maio, Cape Verde",http://dx.doi.org/10.1186/1746-6148-10-91,PMC4005843,24755118,CC BY,"BACKGROUND: Infections caused by canine parvovirus, canine distemper virus and canine coronavirus are an important cause of mortality and morbidity in dogs worldwide. Prior to this study, no information was available concerning the incidence and prevalence of these viruses in Cape Verde archipelago. RESULTS: To provide information regarding the health status of the canine population in Vila do Maio, Maio Island, Cape Verde, 53 rectal swabs were collected from 53 stray dogs during 2010 and 93 rectal swabs and 88 blood samples were collected from 125 stray dogs in 2011. All rectal swabs (2010 n = 53; 2011 n = 93) were analysed for the presence of canine parvovirus, canine distemper virus and canine coronavirus nucleic acids by quantitative PCR methods. Specific antibodies against canine distemper virus and canine parvovirus were also assessed (2011 n = 88). From the 2010 sampling, 43.3% (23/53) were positive for canine parvovirus DNA, 11.3% (6/53) for canine distemper virus RNA and 1.9% (1/53) for canine coronavirus RNA. In 2011, the prevalence values for canine parvovirus and canine coronavirus were quite similar to those from the previous year, respectively 44.1% (41/93), and 1.1% (1/93), but canine distemper virus was not detected in any of the samples analysed (0%, 0/93). Antibodies against canine parvovirus were detected in 71.6% (63/88) blood samples and the seroprevalence found for canine distemper virus was 51.1% (45/88). CONCLUSIONS: This study discloses the data obtained in a molecular and serological epidemiological surveillance carried out in urban populations of stray and domestic animals. Virus transmission and spreading occurs easily in large dog populations leading to high mortality rates particularly in unvaccinated susceptible animals. In addition, these animals can act as disease reservoirs for wild animal populations by occasional contact. Identification of susceptible wildlife of Maio Island is of upmost importance to evaluate the risk of pathogen spill over from domestic to wild animals in Cape Verde and to evaluate the associated threat to the wild susceptible species.",2014 Apr 23,"['Castanheira, Pedro', 'Duarte, Ana', 'Gil, Solange', 'Cartaxeiro, Clara', 'Malta, Manuel', 'Vieira, Sara', 'Tavares, Luis']",BMC Vet Res,,,True
9e5c4cfb4582c7aa5e60455ae948554981054c47,PMC,Lung ultrasound for the diagnosis of pneumonia in adults: a systematic review and meta-analysis,http://dx.doi.org/10.1186/1465-9921-15-50,PMC4005846,24758612,CC BY,"BACKGROUND: Guidelines do not currently recommend the use of lung ultrasound (LUS) as an alternative to chest X-ray (CXR) or chest computerized tomography (CT) scan for the diagnosis of pneumonia. We conducted a meta-analysis to summarize existing evidence of the diagnostic accuracy of LUS for pneumonia in adults. METHODS: We conducted a systematic search of published studies comparing the diagnostic accuracy of LUS against a referent CXR or chest CT scan and/or clinical criteria for pneumonia in adults aged ≥18 years. Eligible studies were required to have a CXR and/or chest CT scan at the time of evaluation. We manually extracted descriptive and quantitative information from eligible studies, and calculated pooled sensitivity and specificity using the Mantel-Haenszel method and pooled positive and negative likelihood ratios (LR) using the DerSimonian-Laird method. We assessed for heterogeneity using the Q and I(2) statistics. RESULTS: Our initial search strategy yielded 2726 articles, of which 45 (1.7%) were manually selected for review and 10 (0.4%) were eligible for analyses. These 10 studies provided a combined sample size of 1172 participants. Six studies enrolled adult patients who were either hospitalized or admitted to Emergency Departments with suspicion of pneumonia and 4 studies enrolled critically-ill adult patients. LUS was performed by highly-skilled sonographers in seven studies, by trained physicians in two, and one did not mention level of training. All studies were conducted in high-income settings. LUS took a maximum of 13 minutes to conduct. Nine studies used a 3.5-5 MHz micro-convex transducer and one used a 5–9 MHz convex probe. Pooled sensitivity and specificity for the diagnosis of pneumonia using LUS were 94% (95% CI, 92%-96%) and 96% (94%-97%), respectively; pooled positive and negative LRs were 16.8 (7.7-37.0) and 0.07 (0.05-0.10), respectively; and, the area-under-the-ROC curve was 0.99 (0.98-0.99). CONCLUSIONS: Our meta-analysis supports that LUS, when conducted by highly-skilled sonographers, performs well for the diagnosis of pneumonia. General practitioners and Emergency Medicine physicians should be encouraged to learn LUS since it appears to be an established diagnostic tool in the hands of experienced physicians.",2014 Apr 23,"['Chavez, Miguel A', 'Shams, Navid', 'Ellington, Laura E', 'Naithani, Neha', 'Gilman, Robert H', 'Steinhoff, Mark C', 'Santosham, Mathuram', 'Black, Robert E', 'Price, Carrie', 'Gross, Margaret', 'Checkley, William']",Respir Res,,,True
a279441c0873b6bfdfbd63cee1220cf9596acaee,PMC,A dose and time response Markov model for the in-host dynamics of infection with intracellular bacteria following inhalation: with application to Francisella tularensis,http://dx.doi.org/10.1098/rsif.2014.0119,PMC4006251,24671937,CC BY,"In a novel approach, the standard birth–death process is extended to incorporate a fundamental mechanism undergone by intracellular bacteria, phagocytosis. The model accounts for stochastic interaction between bacteria and cells of the immune system and heterogeneity in susceptibility to infection of individual hosts within a population. Model output is the dose–response relation and the dose-dependent distribution of time until response, where response is the onset of symptoms. The model is thereafter parametrized with respect to the highly virulent Schu S4 strain of Francisella tularensis, in the first such study to consider a biologically plausible mathematical model for early human infection with this bacterium. Results indicate a median infectious dose of about 23 organisms, which is higher than previously thought, and an average incubation period of between 3 and 7 days depending on dose. The distribution of incubation periods is right-skewed up to about 100 organisms and symmetric for larger doses. Moreover, there are some interesting parallels to the hypotheses of some of the classical dose–response models, such as independent action (single-hit model) and individual effective dose (probit model). The findings of this study support experimental evidence and postulations from other investigations that response is, in fact, influenced by both in-host and between-host variability.",2014 Jun 6,"['Wood, R. M.', 'Egan, J. R.', 'Hall, I. M.']",J R Soc Interface,,,True
3bb7cd6590ad3a1d77205ad58c2c014934ee2364,PMC,Amino acid changes in the spike protein of feline coronavirus correlate with systemic spread of virus from the intestine and not with feline infectious peritonitis,http://dx.doi.org/10.1186/1297-9716-45-49,PMC4006447,24767677,CC BY,"Recent evidence suggests that a mutation in the spike protein gene of feline coronavirus (FCoV), which results in an amino acid change from methionine to leucine at position 1058, may be associated with feline infectious peritonitis (FIP). Tissue and faecal samples collected post mortem from cats diagnosed with or without FIP were subjected to RNA extraction and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) to detect FCoV RNA. In cats with FIP, 95% of tissue, and 81% of faecal samples were PCR-positive, as opposed to 22% of tissue, and 60% of faecal samples in cats without FIP. Relative FCoV copy numbers were significantly higher in the cats with FIP, both in tissues (P < 0.001) and faeces (P = 0.02). PCR-positive samples underwent pyrosequencing encompassing position 1058 of the FCoV spike protein. This identified a methionine codon at position 1058, consistent with the shedding of an enteric form of FCoV, in 77% of the faecal samples from cats with FIP, and in 100% of the samples from cats without FIP. In contrast, 91% of the tissue samples from cats with FIP and 89% from cats without FIP had a leucine codon at position 1058, consistent with a systemic form of FCoV. These results suggest that the methionine to leucine substitution at position 1058 in the FCoV spike protein is indicative of systemic spread of FCoV from the intestine, rather than a virus with the potential to cause FIP.",2014 Apr 25,"['Porter, Emily', 'Tasker, Séverine', 'Day, Michael J', 'Harley, Ross', 'Kipar, Anja', 'Siddell, Stuart G', 'Helps, Christopher R']",Vet Res,,,True
25e53f84ee9bb3d0f9be47a740938c12dbbd559b,PMC,"Evaluation of Antiviral Efficacy of Ribavirin, Arbidol, and T-705 (Favipiravir) in a Mouse Model for Crimean-Congo Hemorrhagic Fever",http://dx.doi.org/10.1371/journal.pntd.0002804,PMC4006714,24786461,CC BY,"BACKGROUND: Mice lacking the type I interferon receptor (IFNAR(−/−) mice) reproduce relevant aspects of Crimean-Congo hemorrhagic fever (CCHF) in humans, including liver damage. We aimed at characterizing the liver pathology in CCHF virus-infected IFNAR(−/−) mice by immunohistochemistry and employed the model to evaluate the antiviral efficacy of ribavirin, arbidol, and T-705 against CCHF virus. METHODOLOGY/PRINCIPAL FINDINGS: CCHF virus-infected IFNAR(−/−) mice died 2–6 days post infection with elevated aminotransferase levels and high virus titers in blood and organs. Main pathological alteration was acute hepatitis with extensive bridging necrosis, reactive hepatocyte proliferation, and mild to moderate inflammatory response with monocyte/macrophage activation. Virus-infected and apoptotic hepatocytes clustered in the necrotic areas. Ribavirin, arbidol, and T-705 suppressed virus replication in vitro by ≥3 log units (IC(50) 0.6–2.8 µg/ml; IC(90) 1.2–4.7 µg/ml). Ribavirin [100 mg/(kg×d)] did not increase the survival rate of IFNAR(−/−) mice, but prolonged the time to death (p<0.001) and reduced the aminotransferase levels and the virus titers. Arbidol [150 mg/(kg×d)] had no efficacy in vivo. Animals treated with T-705 at 1 h [15, 30, and 300 mg/(kg×d)] or up to 2 days [300 mg/(kg×d)] post infection survived, showed no signs of disease, and had no virus in blood and organs. Co-administration of ribavirin and T-705 yielded beneficial rather than adverse effects. CONCLUSIONS/SIGNIFICANCE: Activated hepatic macrophages and monocyte-derived cells may play a role in the proinflammatory cytokine response in CCHF. Clustering of infected hepatocytes in necrotic areas without marked inflammation suggests viral cytopathic effects. T-705 is highly potent against CCHF virus in vitro and in vivo. Its in vivo efficacy exceeds that of the current standard drug for treatment of CCHF, ribavirin.",2014 May 1,"['Oestereich, Lisa', 'Rieger, Toni', 'Neumann, Melanie', 'Bernreuther, Christian', 'Lehmann, Maria', 'Krasemann, Susanne', 'Wurr, Stephanie', 'Emmerich, Petra', 'de Lamballerie, Xavier', 'Ölschläger, Stephan', 'Günther, Stephan']",PLoS Negl Trop Dis,,,True
893e7344ac32678f26385d12f05ab2a06ed3544c,PMC,Emerging Infectious Diseases in Free-Ranging Wildlife–Australian Zoo Based Wildlife Hospitals Contribute to National Surveillance,http://dx.doi.org/10.1371/journal.pone.0095127,PMC4006786,24787430,CC BY,"Emerging infectious diseases are increasingly originating from wildlife. Many of these diseases have significant impacts on human health, domestic animal health, and biodiversity. Surveillance is the key to early detection of emerging diseases. A zoo based wildlife disease surveillance program developed in Australia incorporates disease information from free-ranging wildlife into the existing national wildlife health information system. This program uses a collaborative approach and provides a strong model for a disease surveillance program for free-ranging wildlife that enhances the national capacity for early detection of emerging diseases.",2014 May 1,"['Cox-Witton, Keren', 'Reiss, Andrea', 'Woods, Rupert', 'Grillo, Victoria', 'Baker, Rupert T.', 'Blyde, David J.', 'Boardman, Wayne', 'Cutter, Stephen', 'Lacasse, Claude', 'McCracken, Helen', 'Pyne, Michael', 'Smith, Ian', 'Vitali, Simone', 'Vogelnest, Larry', 'Wedd, Dion', 'Phillips, Martin', 'Bunn, Chris', 'Post, Lyndel']",PLoS One,,,True
a820465dbd9b10702c009445daa65b9bd48e0c72,PMC,Comparison of the Effects of Air Pollution on Outpatient and Inpatient Visits for Asthma: A Population-Based Study in Taiwan,http://dx.doi.org/10.1371/journal.pone.0096190,PMC4006842,24789041,CC BY,"BACKGROUND: A nationwide asthma survey on the effects of air pollution is lacking in Taiwan. The purpose of this study was to evaluate the time trend and the relationship between air pollution and health care services for asthma in Taiwan. METHODS: Health care services for asthma and ambient air pollution data were obtained from the National Health Insurance Research database and Environmental Protection Administration from 2000 through 2009, respectively. Health care services, including those related to the outpatient and inpatient visits were compared according to the concentration of air pollutants. RESULTS: The number of asthma-patient visits to health-care facilities continue to increase in Taiwan. Relative to the respective lowest quartile of air pollutants, the adjusted relative risks (RRs) of the outpatient visits in the highest quartile were 1.10 (P-trend  = 0.013) for carbon monoxide (CO), 1.10 (P-trend  = 0.015) for nitrogen dioxide (NO(2)), and 1.20 (P-trend <0.0001) for particulate matter with an aerodynamic diameter ≦10µm (PM(10)) in the child group (aged 0–18). For adults aged 19–44, the RRs of outpatient visits were 1.13 (P-trend = 0.078) for CO, 1.17 (P-trend = 0.002) for NO(2,) and 1.13 (P-trend <0.0001) for PM(10). For adults aged 45–64, the RRs of outpatient visits were 1.15 (P-trend = 0.003) for CO, 1.19 (P-trend = 0.0002) for NO(2,) and 1.10 (P-trend = 0.001) for PM(10). For the elderly (aged≥ 65), the RRs of outpatient visits in were 1.12 (P-trend  = 0.003) for NO(2) and 1.10 (P-trend  = 0.006) for PM(10.) For inpatient visits, the RRs across quartiles of CO level were 1.00, 1.70, 1.92, and 1.86 (P-trend  = 0.0001) in the child group. There were no significant linear associations between inpatient visits and air pollutants in other groups. CONCLUSIONS: There were positive associations between CO levels and childhood inpatient visits as well as NO(2), CO and PM(10) and outpatient visits.",2014 May 1,"['Pan, Hui-Hsien', 'Chen, Chun-Tzu', 'Sun, Hai-Lun', 'Ku, Min-Sho', 'Liao, Pei-Fen', 'Lu, Ko-Hsiu', 'Sheu, Ji-Nan', 'Huang, Jing-Yang', 'Pai, Jar-Yuan', 'Lue, Ko-Huang']",PLoS One,,,True
4fc5e9665de47ef816e11dea365d068d1d1a77e8,PMC,Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Ion Channel Activity Promotes Virus Fitness and Pathogenesis,http://dx.doi.org/10.1371/journal.ppat.1004077,PMC4006877,24788150,CC BY,"Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) envelope (E) gene attenuates the virus. E gene encodes a small multifunctional protein that possesses ion channel (IC) activity, an important function in virus-host interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARS-CoVs, each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS) leading to death. Reduced edema correlated with lung epithelia integrity and proper localization of Na(+)/K(+) ATPase, which participates in edema resolution. Levels of inflammasome-activated IL-1β were reduced in the lung airways of the animals infected with viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction of IL-1β was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a new determinant for SARS-CoV virulence.",2014 May 1,"['Nieto-Torres, Jose L.', 'DeDiego, Marta L.', 'Verdiá-Báguena, Carmina', 'Jimenez-Guardeño, Jose M.', 'Regla-Nava, Jose A.', 'Fernandez-Delgado, Raul', 'Castaño-Rodriguez, Carlos', 'Alcaraz, Antonio', 'Torres, Jaume', 'Aguilella, Vicente M.', 'Enjuanes, Luis']",PLoS Pathog,,,True
29baaba300edea006f7b4d287edd3426d6573a26,PMC,PARV4: An Emerging Tetraparvovirus,http://dx.doi.org/10.1371/journal.ppat.1004036,PMC4006886,24789326,CC BY,,2014 May 1,"['Matthews, Philippa C.', 'Malik, Amna', 'Simmons, Ruth', 'Sharp, Colin', 'Simmonds, Peter', 'Klenerman, Paul']",PLoS Pathog,,,True
3330a6e81c27b196cb5171baf11239a9560ff6e7,PMC,Respiratory viral pathogens among Singapore military servicemen 2009 – 2012: epidemiology and clinical characteristics,http://dx.doi.org/10.1186/1471-2334-14-204,PMC4006965,24735158,CC BY,"BACKGROUND: Few studies have comprehensively described tropical respiratory disease surveillance in military populations. There is also a lack of studies comparing clinical characteristics of the non-influenza pathogens with influenza and amongst themselves. METHODS: From May 2009 through October 2012, 7733 consenting cases of febrile respiratory illness (FRI) (temperature [greater than or equal to]37.5degreesC with cough or sorethroat) and controls in the Singapore military had clinical data and nasal washes collected prospectively. Nasal washes underwent multiplex PCR, and the analysis was limited to viral mono-infections. RESULTS: 49% of cases tested positive for at least one virus, of whom 10% had multiple infections. 53% of the FRI cases fulfilled the definition of influenza-like illness (ILI), of whom 52% were positive for at least one virus. The most frequent etiologies for mono-infections among FRI cases were Influenza A(H1N1)pdm09 (13%), Influenza B (13%) and coxsackevirus (9%). The sensitivity, specificity, positive predictive value and negative predictive value of ILI for influenza among FRI cases were 72%, 48%, 40% and 69% respectively. On logistic regression, there were marked differences in the prevalence of different symptoms and signs between viruses with fever more prevalent amongst influenza and adenovirus infections than other viruses. CONCLUSION: There are multiple viral etiologies for FRI and ILI with differing clinical symptoms in the Singapore military. Influenza and coxsackevirus were the most common etiology for FRI, while influenza and adenoviruses displayed the most febrile symptoms. Further studies should explore these differences and possible interventions.",2014 Apr 15,"['Tan, Xin Quan', 'Zhao, Xiahong', 'Lee, Vernon J', 'Loh, Jin Phang', 'Tan, Boon Huan', 'Koh, Wee Hong Victor', 'Ng, Sock Hoon', 'Chen, Mark I-Cheng', 'Cook, Alex Richard']",BMC Infect Dis,,,True
b16b23aad25d88c3af9ccd50b754cd4d9e8762fe,PMC,Comparative Analysis of the Effectiveness of Three Immunization Strategies in Controlling Disease Outbreaks in Realistic Social Networks,http://dx.doi.org/10.1371/journal.pone.0095911,PMC4008523,24787718,CC BY,"The high incidence of emerging infectious diseases has highlighted the importance of effective immunization strategies, especially the stochastic algorithms based on local available network information. Present stochastic strategies are mainly evaluated based on classical network models, such as scale-free networks and small-world networks, and thus are insufficient. Three frequently referred stochastic immunization strategies—acquaintance immunization, community-bridge immunization, and ring vaccination—were analyzed in this work. The optimal immunization ratios for acquaintance immunization and community-bridge immunization strategies were investigated, and the effectiveness of these three strategies in controlling the spreading of epidemics were analyzed based on realistic social contact networks. The results show all the strategies have decreased the coverage of the epidemics compared to baseline scenario (no control measures). However the effectiveness of acquaintance immunization and community-bridge immunization are very limited, with acquaintance immunization slightly outperforming community-bridge immunization. Ring vaccination significantly outperforms acquaintance immunization and community-bridge immunization, and the sensitivity analysis shows it could be applied to controlling the epidemics with a wide infectivity spectrum. The effectiveness of several classical stochastic immunization strategies was evaluated based on realistic contact networks for the first time in this study. These results could have important significance for epidemic control research and practice.",2014 May 2,"['Xu, Zhijing', 'Zu, Zhenghu', 'Zheng, Tao', 'Zhang, Wendou', 'Xu, Qing', 'Liu, Jinjie']",PLoS One,,,True
df63d7e1d02197e9dc6686976729bb00682f2ff8,PMC,EV71 vaccines: a milestone in the history of global vaccine development,http://dx.doi.org/10.1038/emi.2014.29,PMC4008769,26038519,CC BY,,2014 Apr 16,"Lu, Shan",Emerg Microbes Infect,,,True
1713f0cf6cf8f5e4134cb4b78d5ab4d2c3cc8791,PMC,Herpes Simplex Virus Hepatitis in an Immunocompetent Adult: A Fatal Outcome due to Liver Failure,http://dx.doi.org/10.1155/2011/138341,PMC4010022,24826316,CC BY,"Objective. To present a case of a healthy 41-year-old female who developed fulminant hepatic failure leading to death. The cause of hepatic failure identified on postmortem exam was herpes simplex virus hepatitis. Design. Observation of a single patient. Setting. Intensive care unit of a tertiary care university teaching hospital in Canada. Patient. 41-year-old previously healthy female presenting with a nonspecific viral illness and systemic inflammatory response syndrome. Intervention. The patient was treated with intravenous fluids and broad-spectrum antibiotics. On the second day of admission, she was found to have elevated transaminases, and, over 48 hours, she progressed to fulminant liver failure with disseminated intravascular coagulopathy, refractory lactic acidosis, and shock. She progressed to respiratory failure requiring intubation and mechanical ventilation. She was started on N-acetylcysteine, a bicarbonate infusion, hemodialysis, and multiple vasopressors and inotropes. Measurements and Main Results. Despite treatment, the patient died roughly 70 hours after her initial presentation to hospital. Her postmortem liver biopsy revealed herpes simplex virus hepatitis as her cause of death. Conclusions. Herpes simplex virus must be considered in all patients presenting with liver failure of unknown cause. If suspected, prompt treatment with acyclovir should be initiated.",2011 Dec 7,"['Poley, Rachel A.', 'Snowdon, Jaime F.', 'Howes, Daniel W.']",Case Rep Crit Care,,,True
4d601f59175ab8d983670ce69504c80be6fb38a4,PMC,Epidemiology of Acute Respiratory Infections in Children in Guangzhou: A Three-Year Study,http://dx.doi.org/10.1371/journal.pone.0096674,PMC4010508,24797911,CC BY,"Acute Respiratory Infections (ARI) are some of the most common human diseases worldwide. However, they have a complex and diverse etiology, and the characteristics of the pathogens involved in respiratory infections in developing countries are not well understood. In this work, we analyzed the characteristics of 17 common respiratory pathogens in children (≤14 years old) with ARI in Guangzhou, southern China over a 3-year period using real-time polymerase chain reaction. Pathogens were identified in 2361/4242 (55.7%) patients, and the positivity rate varied seasonally. Ten of the 17 pathogens investigated showed positivity rates of more than 5%. The most frequently detected pathogens were respiratory syncytial virus (768/2361, 32.5%), influenza A virus (428/2361, 18.1%), enterovirus (138/2361, 13.3%), Mycoplasma pneumoniae (267/2361, 11.3%) and adenovirus (213/2361, 9.0%). Co-pathogens were common and found in 503 of 2361 (21.3%) positive samples. When ranked according to frequency of occurrence, the pattern of co-pathogens was similar to that of the primary pathogens, with the exception of human bocavirus, human coronavirus and human metapneumovirus. Significant differences were found in age prevalence in 10 of the 17 pathogens (p≤0.009): four basic patterns were observed, A: detection rates increased with age, B: detection rates declined with age, C: the detection rate showed distinct peaks or D: numbers of patients were too low to detect a trend or showed no significant difference among age groups (p>0.05). These data will be useful for planning vaccine research and control strategies and for studies predicting pathogen prevalence.",2014 May 5,"['Liu, Wen Kuan', 'Liu, Qian', 'Chen, De Hui', 'Liang, Huan Xi', 'Chen, Xiao Kai', 'Chen, Mei Xin', 'Qiu, Shu Yan', 'Yang, Zi Yeng', 'Zhou, Rong']",PLoS One,,,True
ecea1d9607209bfcf32da251f53136e7f5c12f3e,PMC,A Vaccine of L2 Epitope Repeats Fused with a Modified IgG1 Fc Induced Cross-Neutralizing Antibodies and Protective Immunity against Divergent Human Papillomavirus Types,http://dx.doi.org/10.1371/journal.pone.0095448,PMC4011685,24802101,CC BY,"Current human papillomavirus (HPV) major capsid protein L1 virus-like particles (VLPs)-based vaccines in clinic induce strong HPV type-specific neutralizing antibody responses. To develop pan-HPV vaccines, here, we show that the fusion protein E3R4 consisting of three repeats of HPV16 L2 aa 17–36 epitope (E3) and a modified human IgG1 Fc scaffold (R4) induces cross-neutralizing antibodies and protective immunity against divergent HPV types. E3R4 was expressed as a secreted protein in baculovirus expression system and could be simply purified by one step Protein A affinity chromatography with the purity above 90%. Vaccination of E3R4 formulated with Freunds adjuvant not only induced cross-neutralizing antibodies against HPV pseudovirus types 16, 18, 45, 52, 58, 6, 11 and 5 in mice, but also protected mice against vaginal challenges with HPV pseudovirus types 16, 45, 52, 58, 11 and 5 for at least eleven months after the first immunization. Moreover, vaccination of E3R4 formulated with FDA approved adjuvant alum plus monophosphoryl lipid A also induced cross-neutralizing antibodies against HPV types 16, 18 and 6 in rabbits. Thus, our results demonstrate that delivery of L2 antigen as a modified Fc-fusion protein may facilitate pan-HPV vaccine development.",2014 May 6,"['Chen, Xue', 'Liu, Hongyang', 'Zhang, Ting', 'Liu, Yanchun', 'Xie, Xixiu', 'Wang, Zhirong', 'Xu, Xuemei']",PLoS One,,,True
dc2451c2166ef31db7fc2ad93ade6bf4d18c55e2,PMC,Insights and Ideas Garnered from Marine Metabolites for Development of Dual-Function Acetylcholinesterase and Amyloid-β Aggregation Inhibitors,http://dx.doi.org/10.3390/md12042114,PMC4012451,24714126,CC BY,"Due to the diversity of biological activities that can be found in aquatic ecosystems, marine metabolites have been an active area of drug discovery for the last 30 years. Marine metabolites have been found to inhibit a number of enzymes important in the treatment of human disease. Here, we focus on marine metabolites that inhibit the enzyme acetylcholinesterase, which is the cellular target for treatment of early-stage Alzheimer’s disease. Currently, development of anticholinesterase drugs with improved potency, and drugs that act as dual acetylcholinesterase and amyloid-β aggregation inhibitors, are being sought to treat Alzheimer’s disease. Seven classes of marine metabolites are reported to possess anti-cholinesterase activity. We compared these metabolites to clinically-used acetylcholinesterase inhibitors having known mechanisms of inhibition. We performed a docking simulation and compared them to published experimental data for each metabolite to determine the most likely mechanism of inhibition for each class of marine inhibitor. Our results indicate that several marine metabolites bind to regions of the acetylcholinesterase active site that are not bound by the clinically-used drugs rivastigmine, galanthamine, donepezil, or tacrine. We use the novel poses adopted for computational drug design of tighter binding anticholinesterase drugs likely to act as inhibitors of both acetylcholinesterase activity and amyloid-β aggregation inhibition.",2014 Apr 4,"['Stoddard, Shana V.', 'Hamann, Mark T.', 'Wadkins, Randy M.']",Mar Drugs,,,True
0c490bb2b4f44038ed03a197923aa3490e54f75b,PMC,Insights and Ideas Garnered from Marine Metabolites for Development of Dual-Function Acetylcholinesterase and Amyloid-β Aggregation Inhibitors,http://dx.doi.org/10.3390/md12042114,PMC4012451,24714126,CC BY,"Due to the diversity of biological activities that can be found in aquatic ecosystems, marine metabolites have been an active area of drug discovery for the last 30 years. Marine metabolites have been found to inhibit a number of enzymes important in the treatment of human disease. Here, we focus on marine metabolites that inhibit the enzyme acetylcholinesterase, which is the cellular target for treatment of early-stage Alzheimer’s disease. Currently, development of anticholinesterase drugs with improved potency, and drugs that act as dual acetylcholinesterase and amyloid-β aggregation inhibitors, are being sought to treat Alzheimer’s disease. Seven classes of marine metabolites are reported to possess anti-cholinesterase activity. We compared these metabolites to clinically-used acetylcholinesterase inhibitors having known mechanisms of inhibition. We performed a docking simulation and compared them to published experimental data for each metabolite to determine the most likely mechanism of inhibition for each class of marine inhibitor. Our results indicate that several marine metabolites bind to regions of the acetylcholinesterase active site that are not bound by the clinically-used drugs rivastigmine, galanthamine, donepezil, or tacrine. We use the novel poses adopted for computational drug design of tighter binding anticholinesterase drugs likely to act as inhibitors of both acetylcholinesterase activity and amyloid-β aggregation inhibition.",2014 Apr 4,"['Stoddard, Shana V.', 'Hamann, Mark T.', 'Wadkins, Randy M.']",Mar Drugs,,,False
d2d7428869cef29308728dd3a05f0facaf1d25da,PMC,SARS-CoV envelope protein palmitoylation or nucleocapid association is not required for promoting virus-like particle production,http://dx.doi.org/10.1186/1423-0127-21-34,PMC4014084,24766657,CC BY,"BACKGROUND: Coronavirus membrane (M) proteins are capable of interacting with nucleocapsid (N) and envelope (E) proteins. Severe acute respiratory syndrome coronavirus (SARS-CoV) M co-expression with either N or E is sufficient for producing virus-like particles (VLPs), although at a lower level compared to M, N and E co-expression. Whether E can release from cells or E/N interaction exists so as to contribute to enhanced VLP production is unknown. It also remains to be determined whether E palmitoylation or disulfide bond formation plays a role in SARS-CoV virus assembly. RESULTS: SARS-CoV N is released from cells through an association with E protein-containing vesicles. Further analysis suggests that domains involved in E/N interaction are largely located in both carboxyl-terminal regions. Changing all three E cysteine residues to alanines did not exert negative effects on E release, E association with N, or E enhancement of VLP production, suggesting that E palmitoylation modification or disulfide bond formation is not required for SARS-CoV virus assembly. We found that removal of the last E carboxyl-terminal residue markedly affected E release, N association, and VLP incorporation, but did not significantly compromise the contribution of E to efficient VLP production. CONCLUSIONS: The independence of the SARS-CoV E enhancement effect on VLP production from its viral packaging capacity suggests a distinct SARS-CoV E role in virus assembly.",2014 Apr 27,"['Tseng, Ying-Tzu', 'Wang, Shiu-Mei', 'Huang, Kuo-Jung', 'Wang, Chin-Tien']",J Biomed Sci,,,True
051cf89045450e5eff3fc9ba4fdc518fe1d623b8,PMC,Structural basis of sialidase in complex with geranylated flavonoids as potent natural inhibitors,http://dx.doi.org/10.1107/S1399004714002971,PMC4014123,24816104,CC BY,"Sialidase catalyzes the removal of a terminal sialic acid from glycoconjugates and plays a pivotal role in nutrition, cellular interactions and pathogenesis mediating various infectious diseases including cholera, influenza and sepsis. An array of antiviral sialidase agents have been developed and are commercially available, such as zanamivir and oseltamivir for treating influenza. However, the development of bacterial sialidase inhibitors has been much less successful. Here, natural polyphenolic geranylated flavonoids which show significant inhibitory effects against Cp-NanI, a sialidase from Clostridium perfringens, are reported. This bacterium causes various gastrointestinal diseases. The crystal structure of the Cp-NanI catalytic domain in complex with the best inhibitor, diplacone, is also presented. This structure explains how diplacone generates a stable enzyme–inhibitor complex. These results provide a structural framework for understanding the interaction between sialidase and natural flavonoids, which are promising scaffolds on which to discover new anti-sialidase agents.",2014 Apr 30,"['Lee, Youngjin', 'Ryu, Young Bae', 'Youn, Hyung-Seop', 'Cho, Jung Keun', 'Kim, Young Min', 'Park, Ji-Young', 'Lee, Woo Song', 'Park, Ki Hun', 'Eom, Soo Hyun']",Acta Crystallogr D Biol Crystallogr,,,True
bfa53450da2024fe53e99a919dcadd4f9740a774,PMC,Structural basis of sialidase in complex with geranylated flavonoids as potent natural inhibitors,http://dx.doi.org/10.1107/S1399004714002971,PMC4014123,24816104,CC BY,"Sialidase catalyzes the removal of a terminal sialic acid from glycoconjugates and plays a pivotal role in nutrition, cellular interactions and pathogenesis mediating various infectious diseases including cholera, influenza and sepsis. An array of antiviral sialidase agents have been developed and are commercially available, such as zanamivir and oseltamivir for treating influenza. However, the development of bacterial sialidase inhibitors has been much less successful. Here, natural polyphenolic geranylated flavonoids which show significant inhibitory effects against Cp-NanI, a sialidase from Clostridium perfringens, are reported. This bacterium causes various gastrointestinal diseases. The crystal structure of the Cp-NanI catalytic domain in complex with the best inhibitor, diplacone, is also presented. This structure explains how diplacone generates a stable enzyme–inhibitor complex. These results provide a structural framework for understanding the interaction between sialidase and natural flavonoids, which are promising scaffolds on which to discover new anti-sialidase agents.",2014 Apr 30,"['Lee, Youngjin', 'Ryu, Young Bae', 'Youn, Hyung-Seop', 'Cho, Jung Keun', 'Kim, Young Min', 'Park, Ji-Young', 'Lee, Woo Song', 'Park, Ki Hun', 'Eom, Soo Hyun']",Acta Crystallogr D Biol Crystallogr,,,False
f6069d299d3a03300b5ce41868efc5f2391a7544,PMC,Cellular Superspreaders: An Epidemiological Perspective on HIV Infection inside the Body,http://dx.doi.org/10.1371/journal.ppat.1004092,PMC4014458,24811311,CC BY,,2014 May 8,"['Talbert-Slagle, Kristina', 'Atkins, Katherine E.', 'Yan, Koon-Kiu', 'Khurana, Ekta', 'Gerstein, Mark', 'Bradley, Elizabeth H.', 'Berg, David', 'Galvani, Alison P.', 'Townsend, Jeffrey P.']",PLoS Pathog,,,True
ba2fc738765a5e090d04ad70d972bb35724d927a,PMC,Haemoproteus iwa in Great Frigatebirds (Fregata minor) in the Islands of the Western Indian Ocean,http://dx.doi.org/10.1371/journal.pone.0097185,PMC4014603,24810172,CC BY,"Blood parasites of the sub-genus Haemoproteus have been reported in seabirds, in particular in species in the Suliformes order. These parasites are transmitted by hippoboscid flies of the genus Olfersia; strong specificity has been suggested between the vector and its vertebrate host. We investigated the prevalence of Haemoproteus infection in Suliformes and hippoboscid flies in two oceanic islands of the Western Indian Ocean: Europa and Tromelin. In total, 209 blood samples were collected from great frigatebirds (Fregata minor), masked boobies (Sula dactylatra) and red-footed boobies (Sula sula). Forty-one hippoboscid flies were also collected from birds. Seventeen frigatebirds and one fly collected on Europa tested positive for the presence of Haemoproteus parasites by polymerase chain reaction. Phylogenetic analyses based on partial sequences of the Cytochrome b gene showed that parasites were closely related to Haemoproteus iwa reported from frigatebirds in the Pacific Ocean and in the Caribbean. Plasmodium was also detected in a frigatebird on Europa; however, its placement on the phylogenetic tree could not be resolved. We provide strong support for transmission of blood parasites in seabirds in the Western Indian Ocean and suggest that migrations between the Pacific and the Indian oceans could favor the large-scale distribution of Haemoproteus iwa in frigatebird populations.",2014 May 8,"['Bastien, Matthieu', 'Jaeger, Audrey', 'Le Corre, Matthieu', 'Tortosa, Pablo', 'Lebarbenchon, Camille']",PLoS One,,,True
4cd5e0a3e13b16bea2c7e595e6a77344fa3caebc,PMC,Poxviruses in Bats … so What?,http://dx.doi.org/10.3390/v6041564,PMC4014710,24704730,CC BY,"Poxviruses are important pathogens of man and numerous domestic and wild animal species. Cross species (including zoonotic) poxvirus infections can have drastic consequences for the recipient host. Bats are a diverse order of mammals known to carry lethal viral zoonoses such as Rabies, Hendra, Nipah, and SARS. Consequent targeted research is revealing bats to be infected with a rich diversity of novel viruses. Poxviruses were recently identified in bats and the settings in which they were found were dramatically different. Here, we review the natural history of poxviruses in bats and highlight the relationship of the viruses to each other and their context in the Poxviridae family. In addition to considering the zoonotic potential of these viruses, we reflect on the broader implications of these findings. Specifically, the potential to explore and exploit this newfound relationship to study coevolution and cross species transmission together with fundamental aspects of poxvirus host tropism as well as bat virology and immunology.",2014 Apr 3,"['Baker, Kate S.', 'Murcia, Pablo R.']",Viruses,,,True
bab7ccb9c632b7942584edea0ee9bb3c13f86720,PMC,Poxviruses in Bats … so What?,http://dx.doi.org/10.3390/v6041564,PMC4014710,24704730,CC BY,"Poxviruses are important pathogens of man and numerous domestic and wild animal species. Cross species (including zoonotic) poxvirus infections can have drastic consequences for the recipient host. Bats are a diverse order of mammals known to carry lethal viral zoonoses such as Rabies, Hendra, Nipah, and SARS. Consequent targeted research is revealing bats to be infected with a rich diversity of novel viruses. Poxviruses were recently identified in bats and the settings in which they were found were dramatically different. Here, we review the natural history of poxviruses in bats and highlight the relationship of the viruses to each other and their context in the Poxviridae family. In addition to considering the zoonotic potential of these viruses, we reflect on the broader implications of these findings. Specifically, the potential to explore and exploit this newfound relationship to study coevolution and cross species transmission together with fundamental aspects of poxvirus host tropism as well as bat virology and immunology.",2014 Apr 3,"['Baker, Kate S.', 'Murcia, Pablo R.']",Viruses,,,False
033321dcd825a79a8ba380ba3d52d4ea71f45c81,PMC,Analysis of Determinants in Filovirus Glycoproteins Required for Tetherin Antagonism,http://dx.doi.org/10.3390/v6041654,PMC4014715,24721789,CC BY,"The host cell protein tetherin can restrict the release of enveloped viruses from infected cells. The HIV-1 protein Vpu counteracts tetherin by removing it from the site of viral budding, the plasma membrane, and this process depends on specific interactions between the transmembrane domains of Vpu and tetherin. In contrast, the glycoproteins (GPs) of two filoviruses, Ebola and Marburg virus, antagonize tetherin without reducing surface expression, and the domains in GP required for tetherin counteraction are unknown. Here, we show that filovirus GPs depend on the presence of their authentic transmembrane domains for virus-cell fusion and tetherin antagonism. However, conserved residues within the transmembrane domain were dispensable for membrane fusion and tetherin counteraction. Moreover, the insertion of the transmembrane domain into a heterologous viral GP, Lassa virus GPC, was not sufficient to confer tetherin antagonism to the recipient. Finally, mutation of conserved residues within the fusion peptide of Ebola virus GP inhibited virus-cell fusion but did not ablate tetherin counteraction, indicating that the fusion peptide and the ability of GP to drive host cell entry are not required for tetherin counteraction. These results suggest that the transmembrane domains of filoviral GPs contribute to tetherin antagonism but are not the sole determinants.",2014 Apr 9,"['Gnirß, Kerstin', 'Fiedler, Marie', 'Krämer-Kühl, Annika', 'Bolduan, Sebastian', 'Mittler, Eva', 'Becker, Stephan', 'Schindler, Michael', 'Pöhlmann, Stefan']",Viruses,,,True
84aa85f8690419badcdb6d6777763e6fc3235af1,PMC,Arg(972) Insulin receptor substrate-1 is associated with decreased serum angiotensin-converting enzyme 2 levels in acute myocardial infarction patients: in vivo and in vitro evidence,http://dx.doi.org/10.1186/1475-2840-12-151,PMC4015180,24134599,CC BY,"BACKGROUND: Activation of the renin-angiotensin system (RAS) plays a critical role in the pathophysiology of myocardial infarction (MI) and the development of heart failure. Both angiotensin-converting enzyme 2 (ACE2) and insulin/insulin receptor substrate-1 (IRS-1) show cardioprotective effects after acute MI. The Arg(972) IRS-1 polymorphism is associated with diminished activity of insulin. In the present study, we explored the association among Arg(972) IRS-1, acute MI, and serum levels of ACE2. METHODS: A total of 711 subjects, including 351 subjects with first-time acute MI and 360 subjects without a history of MI were genotyped for Arg(972) IRS-1 polymorphism. Serum levels of ACE2 and MI severity scores were determined. Primary human cardiomyocytes with overexpression of wild type IRS-1 or Arg(972) IRS-1 or knockdown of endogenous IRS-1 were exposed to normoxia and hypoxia, and the expression levels of ACE2 were determined. RESULTS: The serum ACE2 level was significantly increased in acute MI patients compared with that of non-MI controls. Compared with wild type IRS-1 carriers, Arg(972) IRS-1 carriers exhibited decreased serum ACE2 levels and increased MI severity scores after MI. Our in vitro data demonstrate that impairment of insulin/IRS-1/PI3K signaling by overexpression of Arg(972)-IRS-1, knockdown of endogenous IRS-1, or PI3K inhibitor can abolish hypoxia-induced IRS-1-associated PI3K activity and ACE2 expression in human cardiomyocytes, which suggests a causal relationship between Arg(972)-IRS-1 and decreased serum ACE2 levels in acute MI patients. Our in vitro data also indicate that insulin/IRS-1/PI3K signaling is required for ACE2 expression in cardiomyocytes, and that hypoxia can enhance the induction effect of insulin/IRS-1/PI3K signaling on ACE2 expression in cardiomyocytes. CONCLUSIONS: This study provides the first evidence of crosstalk between insulin/IRS-1/PI3K signaling and RAS after acute MI, thereby adding fresh insights into the pathophysiology and treatment of acute MI.",2013 Oct 17,"['Liu, Wei', 'Zhou, Xinmin', 'Yu, Fenglei', 'Hu, Jianguo', 'Hu, Wen']",Cardiovasc Diabetol,,,True
206b5371a11c4b903ed2600b579171a3e6873764,PMC,"Prevalence of adenovirus in children with acute respiratory tract infection in Lanzhou, China",http://dx.doi.org/10.1186/1743-422X-10-271,PMC4015357,23984826,CC BY,"BACKGROUND: Human adenovirus (HAdV) is an important agent causing respiratory tract infection in children. Information on the epidemiological and clinical features of HAdV is limited in children with acute respiratory tract infections (ARTIs) in China, especially those of a novel genotype, Ad55. METHODS: In total, 1169 nasopharyngeal aspirates were collected from children younger than 14 years with ARTIs between November 2006 and November 2009. The polymerase chain reaction (PCR) was used to screen HAdVs. All PCR-positive products were sequenced. RESULTS: 74 of 1169 (6.33%) specimens were positive for HAdVs. Among positive cases, AdV3 (58/74) was detected most frequently, followed by AdV11 (10/74), AdV2 (2/74), AdV7 (2/69), AdV6 (1/74), and AdV1 (1/74). AdV55 was found in one case. The incidence of HAdV infection peaked in children aged 3–7 years. The most common clinical diagnosis was upper respiratory infection, and the most common syndrome was fever and cough.The comparison of HAdV and RSV group revealed that Children infected with group AdV were significant older than children infected with group RSV, had more fever but less frequently wheezing, and cough, crackles, and cyanosis, The duration of hospitalization between the AdV group and RSV group was not significant, but a greater frequency of LRTIs was observed in RSV group. CONCLUSIONS: HAdV is an important viral agent in children with ARTIs in Lanzhou City, China. Multiple HAdV serotypes co-circulated with Ad3, which was predominant in this 3-year study. The novel AdV55 genotype was found in one case. No fixed seasonal rhythm could be identified.",2013 Aug 29,"['Jin, Yu', 'Zhang, Rong-fang', 'Xie, Zhi-ping', 'Yan, Kun-long', 'Gao, Han-chun', 'Song, Jing-rong', 'Yuan, Xin-hui', 'Hou, Yun-de', 'Duan, Zhao-jun']",Virol J,,,True
2a7fdc03389aef740cb9d6de762e96e52473b236,PMC,"Viral aetiology influenza like illnesses in Santa Cruz, Bolivia (2010–2012)",http://dx.doi.org/10.1186/1743-422X-11-35,PMC4015617,24564892,CC BY,"BACKGROUND: Acute respiratory infections represent a serious public health issue worldwide but virological aetiologies of Influenza Like Illnesses (ILIs) remain largely unknown in developing countries. This study represents the first attempt to characterise viral aetiologies of ILIs in Bolivia. METHODS: It was performed in Santa Cruz city from January 2010 to September 2012, based on 564 naso-pharyngeal swabs collected in a National Reference Laboratory and real-time PCR techniques, viral cultures and phylogenetic analyses. RESULTS: 50.2% of samples were positive for at least one virus with influenza viruses (Flu A: ~15%; Flu B: ~9%), rhinoviruses (~8%), coronaviruses (~5%) and hRSV (~4%) being the most frequently identified. The pattern of viral infections varied according to age groups. The elucidation rate was the highest (>60%) amongst patients under 10 yo and the lowest (<40%) amongst patients ≥60 yo. Nearly 3% of samples showed dual viral infections. Epidemiological peaks were associated with a predominant virus but generally included 30-50% of infections by different viruses. Unexpectedly, the frequency of influenza in the 0–4 yo population was very low and a complete hRSV eclipse occurred in 2011. Genetic analyses indicated that distinct evolutionary lineages of Flu A(H1N1)pdm2009, Flu A/H3N2 and Flu B have co-circulated in Bolivia in the study period, originating from Central and North America, Europe, Asia and Australia. CONCLUSION: Our results emphasise the requirement for a reinforced epidemiological and genetic follow-up of influenza and other ILIs in Bolivia to further inform the preparation of vaccines used in the region, guide vaccination campaigns and improve the medical management of patients.",2014 Feb 24,"['Delangue, Julie', 'Roca Sanchez, Yelin', 'Piorkowski, Géraldine', 'Bessaud, Maël', 'Baronti, Cécile', 'Thirion-Perrier, Laurence', 'Mafayle, Roxana Loayza', 'Ardaya, Cinthia Avila', 'Aguilera, Gabriela Añez', 'Guzman, Jimmy Revollo', 'Riera, Javier Lora', 'de Lamballerie, Xavier']",Virol J,,,True
7bfcd661fcd1248cb3ecaeea416eee85a689bf32,PMC,Control of HPV-associated tumors by innovative therapeutic HPV DNA vaccine in the absence of CD4+ T cells,http://dx.doi.org/10.1186/2045-3701-4-11,PMC4015858,24594273,CC BY,"Human papillomavirus (HPV) infections are particularly problematic for HIV + and solid organ transplant patients with compromised CD4+ T cell-dependent immunity as they produce more severe and progressive disease compared to healthy individuals. There are no specific treatments for chronic HPV infection, resulting in an urgent unmet need for a modality that is safe and effective for both immunocompromised and otherwise normal patients with recalcitrant disease. DNA vaccination is attractive because it avoids the risks of administration of live vectors to immunocompromised patients, and can induce potent HPV-specific cytotoxic T cell responses. We have developed a DNA vaccine (pNGVL4a-hCRTE6E7L2) encoding calreticulin (CRT) fused to E6, E7 and L2 proteins of HPV-16, the genotype associated with approximately 90% vaginal, vulvar, anal, penile and oropharyngeal HPV-associated cancers and the majority of cervical cancers. Administration of the DNA vaccine by intramuscular (IM) injection followed by electroporation induced significantly greater HPV-specific immune responses compared to IM injection alone or mixed with alum. Furthermore, pNGVL4a-hCRTE6E7L2 DNA vaccination via electroporation of mice carrying an intravaginal HPV-16 E6/E7-expressing syngeneic tumor demonstrated more potent therapeutic effects than IM vaccination alone. Of note, administration of the DNA vaccine by IM injection followed by electroporation elicited potent E6 and E7-specific CD8+ T cell responses and antitumor effects despite CD4+ T cell-depletion, although no antibody response was detected. While CD4+ T cell-depletion did reduce the E6 and E7-specific CD8+ T cell response, it remained sufficient to prevent subcutaneous tumor growth and to eliminate circulating tumor cells in a model of metastatic HPV-16+ cancer. Thus, the antibody response was CD4-dependent, whereas CD4+ T cell help enhanced the E6/E7-specific CD8+ T cell immunity, but was not required. Taken together, our data suggest that pNGVL4a-hCRTE6E7L2 DNA vaccination via electroporation warrants testing in otherwise healthy patients and those with compromised CD4+ T cell immunity to treat HPV-16-associated anogenital disease and cancer.",2014 Mar 4,"['Peng, Shiwen', 'Song, Liwen', 'Knoff, Jayne', 'Wang, Joshua W', 'Chang, Yung-Nien', 'Hannaman, Drew', 'Wu, T-C', 'Alvarez, Ronald D', 'Roden, Richard BS', 'Hung, Chien-Fu']",Cell Biosci,,,True
b3873c777b754d108ce93d5feca0c3dff4a74564,PMC,"A 60-year review on the changing epidemiology of measles in capital Beijing, China, 1951-2011",http://dx.doi.org/10.1186/1471-2458-13-986,PMC4016557,24143899,CC BY,"BACKGROUND: China pledged to join the global effort to eliminate measles by 2012. To improve measles control strategy, the epidemic trend and population immunity of measles were investigated in 1951–2011 in Beijing. METHODS: The changing trend of measles since 1951 was described based on measles surveillance data from Beijing Centre of Disease Control and Prevention (CDC). The measles vaccination coverage and antibody level were assessed by routinely reported measles vaccination data and twenty-one sero-epidemiological surveys. RESULTS: The incidence of measles has decreased significantly from 593.5/100,000 in 1951 (peaked at 2721.0/100,000 in 1955), to 0.5/100,000 in 2011 due to increasing vaccination coverage of 95%-99%. Incidence rebounded from 6.6/100,000 to 24.5/100,000 since 2005 and decreased after measles vaccine (MV) supplementary immunization activities (SIAs) in 2010. Measles antibody positive rate was 85%-95% in most of years since 1981. High-risk districts were spotted in Chaoyang, Fengtai and Changping districts in recent 15 years. Age-specific incidence and proportion of measles varied over time. The most affected population were younger children of 1–4 years before 1978, older children of 5–14 years in 1978–1996, infant of <1 years and adults of ≥15 years in period of aim to measles elimination. CONCLUSION: Strategies at different stages had a prevailing effect on the epidemic dynamics of measles in recent 60 years in Beijing. It will be essential to validate reported vaccination coverage, improve vaccination coverage in adults and strengthen measles surveillance in the anticipated elimination campaign for measles.",2013 Oct 21,"['Li, Juan', 'Lu, Li', 'Pang, Xinghuo', 'Sun, Meiping', 'Ma, Rui', 'Liu, Donglei', 'Wu, Jiang']",BMC Public Health,,,True
519b82201745afd08726b2c3e87cad65f8409da5,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,True
93c503c5143a7b949665b91e735de908fb437410,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
f8f3b36606fcb6e4275eba987085c94389b6f36e,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
89dc7cd98b98836a8fed26eb42813ef9c8741cb2,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
9091a42a55fd924dbe8273cfdcec30c14e7bb52b,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
8654df96fb9cd8ae9dc157fd4bdbf918760de8a1,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
5374c4e483eccc3bd651bd9391a4a8866654445d,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
5a783fbb41a3064e1bc6e06f18f5a126db1b7e44,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
ec814d30f47d6fe554f3fb65a9813e7028b51b6f,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
249496d6fe8f7583d9614407315177b5b634a6b3,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
95484e01993954fba67480d038aea0558c32573c,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
f6779c3cfe1534b21e84f04a454294add1f755e9,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
e9879104d64146559cc35fdeb001c7c0ea608d2d,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
4930fc9d9e3cb5bea0a97320187aca766f07493d,PMC,Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus,http://dx.doi.org/10.1186/1743-422X-11-82,PMC4018502,24885320,CC BY,"BACKGROUND: Public health risks associated to infection by human coronaviruses remain considerable and vaccination is a key option for preventing the resurgence of severe acute respiratory syndrome coronavirus (SARS-CoV). We have previously reported that antibodies elicited by a SARS-CoV vaccine candidate based on recombinant, full-length SARS-CoV Spike-protein trimers, trigger infection of immune cell lines. These observations prompted us to investigate the molecular mechanisms and responses to antibody-mediated infection in human macrophages. METHODS: We have used primary human immune cells to evaluate their susceptibility to infection by SARS-CoV in the presence of anti-Spike antibodies. Fluorescence microscopy and real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) were utilized to assess occurrence and consequences of infection. To gain insight into the underlying molecular mechanism, we performed mutational analysis with a series of truncated and chimeric constructs of fragment crystallizable γ receptors (FcγR), which bind antibody-coated pathogens. RESULTS: We show here that anti-Spike immune serum increased infection of human monocyte-derived macrophages by replication-competent SARS-CoV as well as Spike-pseudotyped lentiviral particles (SARS-CoVpp). Macrophages infected with SARS-CoV, however, did not support productive replication of the virus. Purified anti-viral IgGs, but not other soluble factor(s) from heat-inactivated mouse immune serum, were sufficient to enhance infection. Antibody-mediated infection was dependent on signaling-competent members of the human FcγRII family, which were shown to confer susceptibility to otherwise naïve ST486 cells, as binding of immune complexes to cell surface FcγRII was necessary but not sufficient to trigger antibody-dependent enhancement (ADE) of infection. Furthermore, only FcγRII with intact cytoplasmic signaling domains were competent to sustain ADE of SARS-CoVpp infection, thus providing additional information on the role of downstream signaling by FcγRII. CONCLUSIONS: These results demonstrate that human macrophages can be infected by SARS-CoV as a result of IgG-mediated ADE and indicate that this infection route requires signaling pathways activated downstream of binding to FcγRII receptors.",2014 May 6,"['Yip, Ming Shum', 'Leung, Nancy Hiu Lan', 'Cheung, Chung Yan', 'Li, Ping Hung', 'Lee, Horace Hok Yeung', 'Daëron, Marc', 'Peiris, Joseph Sriyal Malik', 'Bruzzone, Roberto', 'Jaume, Martial']",Virol J,,,True
b40b2c7a9a57323d18e7b564d0dec8ee330d3d01,PMC,Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1,http://dx.doi.org/10.7554/eLife.02362,PMC4018625,24843023,CC BY,"BST2/tetherin, an antiviral restriction factor, inhibits the release of enveloped viruses from the cell surface. Human immunodeficiency virus-1 (HIV-1) antagonizes BST2 through viral protein u (Vpu), which downregulates BST2 from the cell surface. We report the crystal structure of a protein complex containing Vpu and BST2 cytoplasmic domains and the core of the clathrin adaptor protein complex 1 (AP1). This, together with our biochemical and functional validations, reveals how Vpu hijacks the AP1-dependent membrane trafficking pathways to mistraffick BST2. Vpu mimics a canonical acidic dileucine-sorting motif to bind AP1 in the cytosol, while simultaneously interacting with BST2 in the membrane. These interactions enable Vpu to build on an intrinsic interaction between BST2 and AP1, presumably causing the observed retention of BST2 in juxtanuclear endosomes and stimulating its degradation in lysosomes. The ability of Vpu to hijack AP-dependent trafficking pathways suggests a potential common theme for Vpu-mediated downregulation of host proteins. DOI: http://dx.doi.org/10.7554/eLife.02362.001",2014 Apr 29,"['Jia, Xiaofei', 'Weber, Erin', 'Tokarev, Andrey', 'Lewinski, Mary', 'Rizk, Maryan', 'Suarez, Marissa', 'Guatelli, John', 'Xiong, Yong']",eLife,,,True
1b2d0c795271b2dffeba58396e52cca462185d78,PMC,Communicating and Monitoring Surveillance and Response Activities for Malaria Elimination: China's “1-3-7” Strategy,http://dx.doi.org/10.1371/journal.pmed.1001642,PMC4019513,24824170,CC BY,"Qi Gao and colleagues describe China's 1-3-7 strategy for eliminating malaria: reporting of malaria cases within one day, their confirmation and investigation within three days, and the appropriate public health response to prevent further transmission within seven days.",2014 May 13,"['Cao, Jun', 'Sturrock, Hugh J. W.', 'Cotter, Chris', 'Zhou, Shuisen', 'Zhou, Huayun', 'Liu, Yaobao', 'Tang, Linhua', 'Gosling, Roly D.', 'Feachem, Richard G. A.', 'Gao, Qi']",PLoS Med,,,True
1ab0742b23affe5d2f9a5adc6b98e3f89defd930,PMC,Usefulness of Cellular Analysis of Bronchoalveolar Lavage Fluid for Predicting the Etiology of Pneumonia in Critically Ill Patients,http://dx.doi.org/10.1371/journal.pone.0097346,PMC4019586,24824328,CC BY,"BACKGROUND: The usefulness of bronchoalveolar lavage (BAL) fluid cellular analysis in pneumonia has not been adequately evaluated. This study investigated the ability of cellular analysis of BAL fluid to differentially diagnose bacterial pneumonia from viral pneumonia in adult patients who are admitted to intensive care unit. METHODS: BAL fluid cellular analysis was evaluated in 47 adult patients who underwent bronchoscopic BAL following less than 24 hours of antimicrobial agent exposure. The abilities of BAL fluid total white blood cell (WBC) counts and differential cell counts to differentiate between bacterial and viral pneumonia were evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Bacterial pneumonia (n = 24) and viral pneumonia (n = 23) were frequently associated with neutrophilic pleocytosis in BAL fluid. BAL fluid median total WBC count (2,815/µL vs. 300/µL, P<0.001) and percentage of neutrophils (80.5% vs. 54.0%, P = 0.02) were significantly higher in the bacterial pneumonia group than in the viral pneumonia group. In ROC curve analysis, BAL fluid total WBC count showed the best discrimination, with an area under the curve of 0.855 (95% CI, 0.750–0.960). BAL fluid total WBC count ≥510/µL had a sensitivity of 83.3%, specificity of 78.3%, positive likelihood ratio (PLR) of 3.83, and negative likelihood ratio (NLR) of 0.21. When analyzed in combination with serum procalcitonin or C-reactive protein, sensitivity was 95.8%, specificity was 95.7%, PLR was 8.63, and NLR was 0.07. BAL fluid total WBC count ≥510/µL was an independent predictor of bacterial pneumonia with an adjusted odds ratio of 13.5 in multiple logistic regression analysis. CONCLUSIONS: Cellular analysis of BAL fluid can aid early differential diagnosis of bacterial pneumonia from viral pneumonia in critically ill patients.",2014 May 13,"['Choi, Sang-Ho', 'Hong, Sang-Bum', 'Hong, Hyo-Lim', 'Kim, Sung-Han', 'Huh, Jin Won', 'Sung, Heungsup', 'Lee, Sang-Oh', 'Kim, Mi-Na', 'Jeong, Jin-Yong', 'Lim, Chae-Man', 'Kim, Yang Soo', 'Woo, Jun Hee', 'Koh, Younsuck']",PLoS One,,,True
1f1c43d3f7a43ad4a16b8ded2b2ac384f3db3b4c,PMC,It is Unlikely That Influenza Viruses Will Cause a Pandemic Again Like What Happened in 1918 and 1919,http://dx.doi.org/10.3389/fpubh.2014.00039,PMC4019839,24847476,CC BY,,2014 May 7,"Song, Liting",Front Public Health,,,True
540a2a909e0ae17de908c236742379d073ab2d95,PMC,Evaluation of Three Automated Nucleic Acid Extraction Systems for Identification of Respiratory Viruses in Clinical Specimens by Multiplex Real-Time PCR,http://dx.doi.org/10.1155/2014/430650,PMC4020539,24868527,CC BY,"A total of 84 nasopharyngeal swab specimens were collected from 84 patients. Viral nucleic acid was extracted by three automated extraction systems: QIAcube (Qiagen, Germany), EZ1 Advanced XL (Qiagen), and MICROLAB Nimbus IVD (Hamilton, USA). Fourteen RNA viruses and two DNA viruses were detected using the Anyplex II RV16 Detection kit (Seegene, Republic of Korea). The EZ1 Advanced XL system demonstrated the best analytical sensitivity for all the three viral strains. The nucleic acids extracted by EZ1 Advanced XL showed higher positive rates for virus detection than the others. Meanwhile, the MICROLAB Nimbus IVD system was comprised of fully automated steps from nucleic extraction to PCR setup function that could reduce human errors. For the nucleic acids recovered from nasopharyngeal swab specimens, the QIAcube system showed the fewest false negative results and the best concordance rate, and it may be more suitable for detecting various viruses including RNA and DNA virus strains. Each system showed different sensitivity and specificity for detection of certain viral pathogens and demonstrated different characteristics such as turnaround time and sample capacity. Therefore, these factors should be considered when new nucleic acid extraction systems are introduced to the laboratory.",2014 Apr 28,"['Kim, Yoonjung', 'Han, Mi-Soon', 'Kim, Juwon', 'Kwon, Aerin', 'Lee, Kyung-A']",Biomed Res Int,,,True
b7f783ce7fc3715b718384a9295bd8afb24b93ec,PMC,"Respiratory viruses associated with patients older than 50 years presenting with ILI in Senegal, 2009 to 2011",http://dx.doi.org/10.1186/1471-2334-14-189,PMC4020602,24712515,CC BY,"BACKGROUND: In Africa, especially in West Africa, studies about the prevalence and diversity of respiratory viruses (influenza and others) in elderly people are largely lacking. In studies done elsewhere, it is well established that older people, when compared with younger adults, are at greater risk of significant morbidity and mortality from complications arising from influenza. The main aim of this study was to determine the prevalence and the diversity of respiratory viruses associated with ILI cases in adults over 50 years old in Senegal. METHODS: The recruitment period of this study was from January 2009 to December 2011. 232 patients aged 50 years and above presenting ILI cases were enrolled. Nasal-pharyngeal and/or oral pharyngeal swabs were collected from patients. RNA was extracted from 200 μl of each sample followed by a two-step real-time RT-PCR. The Anyplex™ II RV16 Detection kit was used for viral detection. The kit enabled the simultaneous detection of the presence of 16 respiratory viruses. RESULTS: 150 viruses were detected: influenza viruses (44.7%) and rhinoviruses (26.7%) were the most prevalent. We detected 13 human parainfluenza viruses (8.7%), 7 human respiratory syncytial viruses (4.7%), 6 coronaviruses (4%), 5 human metapneumoviruses (3.3%), 5 human adenoviruses (3.3%) and 1 human bocavirus (0.7%). 14 cases (6%) of dual virus infections and one triple viral detection case were encountered. 56 (56.6%) viruses detected were found in the 50-64 year old age group, 59 (76.6%; P < 0.001) from 65–74 year old age group and 35 (62.5%) were detected in the ≥75 year old age group. The viral co-infections were more frequent in the 65-74 age group (9/15). CONCLUSIONS: This pilot study demonstrates a variety of respiratory viruses in the elderly. It also highlights a high prevalence of these viruses in this age group. We speculate from these results that the impact of respiratory viruses other than influenza on the elderly has been considerably underestimated. A more exhaustive study seems necessary in order to provide a more complete picture of the burden of respiratory viruses on morbidity among adults over 50 years old in the sub-Saharan context.",2014 Apr 8,"['Dia, Ndongo', 'Richard, Vincent', 'Kiori, Davy', 'Cisse, El Hadj Abdoul Khadir', 'Sarr, Fatoumata Diène', 'Faye, Abdourahmane', 'Goudiaby, Déborah G', 'Diop, Ousmane M', 'Niang, Mbayame N']",BMC Infect Dis,,,True
a27702025191a260051091b84a0d5c9b68829440,PMC,"The Antiviral Restriction Factors IFITM1, 2 and 3 Do Not Inhibit Infection of Human Papillomavirus, Cytomegalovirus and Adenovirus",http://dx.doi.org/10.1371/journal.pone.0096579,PMC4020762,24827144,CC BY,"Type I interferons (IFN-α and β) induce dynamic host defense mechanisms to inhibit viral infections. It has been recently recognized that the interferon-inducible transmembrane proteins (IFITM) 1, 2 and 3 can block entry of a broad spectrum of RNA viruses. However, no study to date has focused on the role of IFITM proteins in DNA virus restriction. Here, we demonstrate that IFN-α or -β treatment of keratinocytes substantially decreases human papillomavirus 16 (HPV16) infection while robustly inducing IFITM1, 2 and 3 expression. However, IFITM1, 2 and 3 overexpression did not inhibit HPV16 infection; rather, IFITM1 and IFITM3 modestly enhanced HPV16 infection in various cell types including primary keratinocytes. Moreover, IFITM1, 2 and 3 did not inhibit infection by two other DNA viruses, human cytomegalovirus (HCMV) and adenovirus type 5 (Ad5). Taken together, we reveal that the entry of several DNA viruses, including HPV, HCMV, and Ad5 is not affected by IFITM1, 2 and 3 expression. These results imply that HPV, and other DNA viruses, may bypass IFITM restriction during intracellular trafficking.",2014 May 14,"['Warren, Cody J.', 'Griffin, Laura M.', 'Little, Alexander S.', 'Huang, I-Chueh', 'Farzan, Michael', 'Pyeon, Dohun']",PLoS One,,,True
866fb412a1ef52e7696d7a50400760ad00b0db9f,PMC,"The Antiviral Restriction Factors IFITM1, 2 and 3 Do Not Inhibit Infection of Human Papillomavirus, Cytomegalovirus and Adenovirus",http://dx.doi.org/10.1371/journal.pone.0096579,PMC4020762,24827144,CC BY,"Type I interferons (IFN-α and β) induce dynamic host defense mechanisms to inhibit viral infections. It has been recently recognized that the interferon-inducible transmembrane proteins (IFITM) 1, 2 and 3 can block entry of a broad spectrum of RNA viruses. However, no study to date has focused on the role of IFITM proteins in DNA virus restriction. Here, we demonstrate that IFN-α or -β treatment of keratinocytes substantially decreases human papillomavirus 16 (HPV16) infection while robustly inducing IFITM1, 2 and 3 expression. However, IFITM1, 2 and 3 overexpression did not inhibit HPV16 infection; rather, IFITM1 and IFITM3 modestly enhanced HPV16 infection in various cell types including primary keratinocytes. Moreover, IFITM1, 2 and 3 did not inhibit infection by two other DNA viruses, human cytomegalovirus (HCMV) and adenovirus type 5 (Ad5). Taken together, we reveal that the entry of several DNA viruses, including HPV, HCMV, and Ad5 is not affected by IFITM1, 2 and 3 expression. These results imply that HPV, and other DNA viruses, may bypass IFITM restriction during intracellular trafficking.",2014 May 14,"['Warren, Cody J.', 'Griffin, Laura M.', 'Little, Alexander S.', 'Huang, I-Chueh', 'Farzan, Michael', 'Pyeon, Dohun']",PLoS One,,,False
fb9b75c5e290a5ff3b49c2f0f93e05a1dcff78df,PMC,Tollip or Not Tollip: What Are the Evolving Questions behind It?,http://dx.doi.org/10.1371/journal.pone.0097219,PMC4020778,24828816,CC BY,"Tollip plays an important role in the interleukin-1 receptor IL-1R and Toll pathways. As a modulator of the immune pathway, it indirectly controls the amount of antimicrobial peptides. This could indicate a vital step in maintaining animal immune systems and preventing infection. Evolutionary questions are crucial to understanding the conservation and functioning of the biochemical pathways like the Tollip-mediated one. Through an analysis of 36 sequences of the Tollip protein from different animal taxa, downloaded from Kyoto Encyclopedia of Genes and Genomes (KEGG) databank, we inferred diverse evolutionary parameters, such as molecular selection and structure conservation, by analyzing residue by residue, beyond the canonical parameters to this type of study, as maximum likelihood trees. We found that Tollip presented different trends in its evolving history. In primates, the protein is becoming more unstable, just the opposite is observed in the arthropod group. The most interesting finding was the concentration of positively selected residues at amino terminal ends. Some observed topological incongruences in maximum likelihood trees of complete and curated Tollip data sets could be explained through horizontal transfers, evidenced by recombination detection. These results suggest that there is more to be researched and understood about this protein.",2014 May 14,"['Luiz, Denis Prudencio', 'Santos Júnior, Célio Dias', 'Bonetti, Ana Maria', 'Brandeburgo, Malcom Antônio Manfredi']",PLoS One,,,True
d65ef4b00759d797d28454625b4de2814675bb56,PMC,Interferon-induced HERC5 is evolving under positive selection and inhibits HIV-1 particle production by a novel mechanism targeting Rev/RRE-dependent RNA nuclear export,http://dx.doi.org/10.1186/1742-4690-11-27,PMC4021598,24693865,CC BY,"BACKGROUND: Type I interferon (IFN) inhibits virus replication by activating multiple antiviral mechanisms and pathways. It has long been recognized that type I IFNs can potently block HIV-1 replication in vitro; as such, HIV-1 has been used as a system to identify and characterize IFN-induced antiviral proteins responsible for this block. IFN-induced HERC5 contains an amino-terminal Regulator of Chromosome Condensation 1 (RCC1)-like domain and a carboxyl-terminal Homologous to the E6-AP Carboxyl Terminus (HECT) domain. HERC5 is the main cellular E3 ligase that conjugates the IFN-induced protein ISG15 to proteins. This E3 ligase activity was previously shown to inhibit the replication of evolutionarily diverse viruses, including HIV-1. The contribution of the RCC1-like domain to the antiviral activity of HERC5 was previously unknown. RESULTS: In this study, we showed that HERC5 inhibits HIV-1 particle production by a second distinct mechanism that targets the nuclear export of Rev/RRE-dependent RNA. Unexpectedly, the E3 ligase activity of HERC5 was not required for this inhibition. Instead, this activity required the amino-terminal RCC1-like domain of HERC5. Inhibition correlated with a reduction in intracellular RanGTP protein levels and/or the ability of RanGTP to interact with RanBP1. Inhibition also correlated with altered subcellular localization of HIV-1 Rev. In addition, we demonstrated that positive evolutionary selection is operating on HERC5. We identified a region in the RCC1-like domain that exhibits an exceptionally high probability of having evolved under positive selection and showed that this region is required for HERC5-mediated inhibition of nuclear export. CONCLUSIONS: We have identified a second distinct mechanism by which HERC5 inhibits HIV-1 replication and demonstrate that HERC5 is evolving under strong positive selection. Together, our findings contribute to a growing body of evidence suggesting that HERC5 is a novel host restriction factor.",2014 Apr 3,"['Woods, Matthew William', 'Tong, Jessica Gayle', 'Tom, Sean Kevin', 'Szabo, Peter Anthony', 'Cavanagh, Peter Craig', 'Dikeakos, Jimmy Dimitrios', 'Haeryfar, SM Mansour', 'Barr, Stephen Dominic']",Retrovirology,,,True
d20b60ebfc43e34474624c454c84afb31ddec20c,PMC,Interferon-induced HERC5 is evolving under positive selection and inhibits HIV-1 particle production by a novel mechanism targeting Rev/RRE-dependent RNA nuclear export,http://dx.doi.org/10.1186/1742-4690-11-27,PMC4021598,24693865,CC BY,"BACKGROUND: Type I interferon (IFN) inhibits virus replication by activating multiple antiviral mechanisms and pathways. It has long been recognized that type I IFNs can potently block HIV-1 replication in vitro; as such, HIV-1 has been used as a system to identify and characterize IFN-induced antiviral proteins responsible for this block. IFN-induced HERC5 contains an amino-terminal Regulator of Chromosome Condensation 1 (RCC1)-like domain and a carboxyl-terminal Homologous to the E6-AP Carboxyl Terminus (HECT) domain. HERC5 is the main cellular E3 ligase that conjugates the IFN-induced protein ISG15 to proteins. This E3 ligase activity was previously shown to inhibit the replication of evolutionarily diverse viruses, including HIV-1. The contribution of the RCC1-like domain to the antiviral activity of HERC5 was previously unknown. RESULTS: In this study, we showed that HERC5 inhibits HIV-1 particle production by a second distinct mechanism that targets the nuclear export of Rev/RRE-dependent RNA. Unexpectedly, the E3 ligase activity of HERC5 was not required for this inhibition. Instead, this activity required the amino-terminal RCC1-like domain of HERC5. Inhibition correlated with a reduction in intracellular RanGTP protein levels and/or the ability of RanGTP to interact with RanBP1. Inhibition also correlated with altered subcellular localization of HIV-1 Rev. In addition, we demonstrated that positive evolutionary selection is operating on HERC5. We identified a region in the RCC1-like domain that exhibits an exceptionally high probability of having evolved under positive selection and showed that this region is required for HERC5-mediated inhibition of nuclear export. CONCLUSIONS: We have identified a second distinct mechanism by which HERC5 inhibits HIV-1 replication and demonstrate that HERC5 is evolving under strong positive selection. Together, our findings contribute to a growing body of evidence suggesting that HERC5 is a novel host restriction factor.",2014 Apr 3,"['Woods, Matthew William', 'Tong, Jessica Gayle', 'Tom, Sean Kevin', 'Szabo, Peter Anthony', 'Cavanagh, Peter Craig', 'Dikeakos, Jimmy Dimitrios', 'Haeryfar, SM Mansour', 'Barr, Stephen Dominic']",Retrovirology,,,False
7967040b2131b69fec61d9f1d5c14dd214c49989,PMC,A look at the ASEAN-NDI: building a regional health R&D innovation network,http://dx.doi.org/10.1186/2049-9957-3-15,PMC4021759,24834349,CC BY,"Globally, there are growing efforts to address diseases through the advancement in health research and development (R&D), strengthening of regional cooperation in science and technology (particularly on product discovery and development), and implementation of the World Health Assembly Resolution 61.21 (WHA61.21) on the Global Strategy and Plan of Action on Public Health, Innovation, and Intellectual Property (GSPA-PHI). As such, the Association of Southeast Asian Nations (ASEAN) is responding to this through the establishment of the ASEAN-Network for Drugs, Diagnostics, Vaccines, and Traditional Medicines Innovation (ASEAN-NDI). This is important in the ASEAN considering that infectious tropical diseases remain prevalent, emerging, and reemerging in the region. This paper looks into the evolution of the ASEAN-NDI from its inception in 2009, to how it is at present, and its plans to mitigate public health problems regionally and even globally.",2014 Apr 28,"['Montoya, Jaime C', 'Rebulanan, Carina L', 'Parungao, Nico Angelo C', 'Ramirez, Bernadette']",Infect Dis Poverty,,,True
39c02a3753a3488525c47e79c1f0eddf16195ebb,PMC,A look at the ASEAN-NDI: building a regional health R&D innovation network,http://dx.doi.org/10.1186/2049-9957-3-15,PMC4021759,24834349,CC BY,"Globally, there are growing efforts to address diseases through the advancement in health research and development (R&D), strengthening of regional cooperation in science and technology (particularly on product discovery and development), and implementation of the World Health Assembly Resolution 61.21 (WHA61.21) on the Global Strategy and Plan of Action on Public Health, Innovation, and Intellectual Property (GSPA-PHI). As such, the Association of Southeast Asian Nations (ASEAN) is responding to this through the establishment of the ASEAN-Network for Drugs, Diagnostics, Vaccines, and Traditional Medicines Innovation (ASEAN-NDI). This is important in the ASEAN considering that infectious tropical diseases remain prevalent, emerging, and reemerging in the region. This paper looks into the evolution of the ASEAN-NDI from its inception in 2009, to how it is at present, and its plans to mitigate public health problems regionally and even globally.",2014 Apr 28,"['Montoya, Jaime C', 'Rebulanan, Carina L', 'Parungao, Nico Angelo C', 'Ramirez, Bernadette']",Infect Dis Poverty,,,False
2f4ea657c6c2e9ee90b6ef1af40e2626e5bb488b,PMC,Potential Sources and Roles of Adaptive Immunity in Age-Related Macular Degeneration: Shall We Rename AMD into Autoimmune Macular Disease?,http://dx.doi.org/10.1155/2014/532487,PMC4022009,24876950,CC BY,"Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly throughout the industrialized world. Its most prominent pathologic features are lesions involving the retinal pigment epithelium (RPE) the Bruch's membrane, the degeneration of photoreceptors, and, in the most aggressive cases, choroidal neovascularization. Genetic associations between the risk of developing AMD and polymorphism within components of the complement system, as well as chemokine receptors expressed on microglial cells and macrophages, have linked retinal degeneration and choroidal neovascularization to innate immunity (inflammation). In addition to inflammation, players of the adaptive immunity including cytokines, chemokines, antibodies, and T cells have been detected in animal models of AMD and in patients suffering from this pathology. These observations suggest that adaptive immunity might play a role in different processes associated with AMD such as RPE atrophy, neovascularization, and retinal degeneration. To this date however, the exact roles (if any) of autoantibodies and T cells in AMD remain unknown. In this review we discuss the potential effects of adaptive immune responses in AMD pathogenesis.",2014 Apr 30,"Camelo, Serge",Autoimmune Dis,,,True
6e4a162ab67f96a6b889e1f09d5531770fb1996d,PMC,An RNA Aptamer That Specifically Binds to the Glycosylated Hemagglutinin of Avian Influenza Virus and Suppresses Viral Infection in Cells,http://dx.doi.org/10.1371/journal.pone.0097574,PMC4023947,24835440,CC BY,"The influenza virus surface glycoprotein hemagglutinin (HA) is responsible for viral attachment to sialic acid-containing host cell receptors and it facilitates the initial stage of viral infection. In the present study, we isolated an RNA aptamer specific to the glycosylated receptor-binding domain of the HA protein (gHA1) after 12 cycles of the systematic evolution of ligands by exponential enrichment procedure (SELEX), and we then investigated if the selected aptamer suppresses viral infection in host cells. Nitrocellulose filter binding and enzyme-linked immunosorbent assay (ELISA) experiments revealed that 1 RNA aptamer, HA12-16, bound specifically to the gHA1 protein. Cell viability assay showed that the HA12-16 RNA aptamer suppressed viral infection in host cells by enhancing cell viability. Immunofluorescence microscopic analysis further demonstrated that the HA12-16 RNA aptamer suppresses viral attachment to host cells by neutralizing the receptor-binding site of influenza virus HA. These results indicate that the isolated RNA aptamer can be developed as an antiviral reagent against influenza through appropriate therapeutic formulation.",2014 May 16,"['Kwon, Hyun-Mi', 'Lee, Kwang Hyun', 'Han, Byung Woo', 'Han, Mi Ra', 'Kim, Dong Ho', 'Kim, Dong-Eun']",PLoS One,,,True
c40606c62e96d3ea8313b67bf60e8148eeb45f05,PMC,After 2015: infectious diseases in a new era of health and development,http://dx.doi.org/10.1098/rstb.2013.0426,PMC4024220,24821913,CC BY,"Running over timescales that span decades or centuries, the epidemiological transition provides the central narrative of global health. In this transition, a reduction in mortality is followed by a reduction in fertility, creating larger, older populations in which the main causes of illness and death are no longer acute infections of children but chronic diseases of adults. Since the year 2000, the Millennium Development Goals (MDGs) have provided a framework for accelerating the decline of infectious diseases, backed by a massive injection of foreign investment to low-income countries. Despite the successes of the MDGs era, the inhabitants of low-income countries still suffer an enormous burden of disease owing to diarrhoea, pneumonia, HIV/AIDS, tuberculosis, malaria and other pathogens. Adding to the predictable burden of endemic disease, the threat of pandemics is ever-present and global. With a view to the future, this review spotlights five aspects of the fight against infection beyond 2015, when the MDGs will be replaced by a new set of goals for poverty reduction and sustainable development. These aspects are: exploiting the biological links between infectious and non-infectious diseases; controlling infections among the new urban majority; enhancing the response to international health threats; expanding childhood immunization programmes to prevent acute and chronic diseases in adults; and working towards universal health coverage. By scanning the wider horizon now, infectious disease specialists have the chance to shape the post-2015 era of health and development.",2014 Jun 19,"Dye, Christopher",Philos Trans R Soc Lond B Biol Sci,,,True
ecb3c8e94fb9e56b8ca7f05687f791f3db024a94,PMC,Social mixing patterns in rural and urban areas of southern China,http://dx.doi.org/10.1098/rspb.2014.0268,PMC4024290,24789897,CC BY,"A dense population, global connectivity and frequent human–animal interaction give southern China an important role in the spread and emergence of infectious disease. However, patterns of person-to-person contact relevant to the spread of directly transmitted infections such as influenza remain poorly quantified in the region. We conducted a household-based survey of travel and contact patterns among urban and rural populations of Guangdong, China. We measured the character and distance from home of social encounters made by 1821 individuals. Most individuals reported 5–10 h of contact with around 10 individuals each day; however, both distributions have long tails. The distribution of distance from home at which contacts were made is similar: most were within a kilometre of the participant's home, while some occurred further than 500 km away. Compared with younger individuals, older individuals made fewer contacts which tended to be closer to home. There was strong assortativity in age-based contact rates. We found no difference between the total number or duration of contacts between urban and rural participants, but urban participants tended to make contacts closer to home. These results can improve mathematical models of infectious disease emergence, spread and control in southern China and throughout the region.",2014 Jun 22,"['Read, Jonathan M.', 'Lessler, Justin', 'Riley, Steven', 'Wang, Shuying', 'Tan, Li Jiu', 'Kwok, Kin On', 'Guan, Yi', 'Jiang, Chao Qiang', 'Cummings, Derek A. T.']",Proc Biol Sci,,,True
15dddee0b99b7095553fde91f32e7ae83c15e9ef,PMC,European Monitoring Systems and Data for Assessing Environmental and Climate Impacts on Human Infectious Diseases,http://dx.doi.org/10.3390/ijerph110403894,PMC4025019,24722542,CC BY,"Surveillance is critical to understanding the epidemiology and control of infectious diseases. The growing concern over climate and other drivers that may increase infectious disease threats to future generations has stimulated a review of the surveillance systems and environmental data sources that might be used to assess future health impacts from climate change in Europe. We present an overview of organizations, agencies and institutions that are responsible for infectious disease surveillance in Europe. We describe the surveillance systems, tracking tools, communication channels, information exchange and outputs in light of environmental and climatic drivers of infectious diseases. We discuss environmental and climatic data sets that lend themselves to epidemiological analysis. Many of the environmental data sets have a relatively uniform quality across EU Member States because they are based on satellite measurements or EU funded FP6 or FP7 projects with full EU coverage. Case-reporting systems for surveillance of infectious diseases should include clear and consistent case definitions and reporting formats that are geo-located at an appropriate resolution. This will allow linkage to environmental, social and climatic sources that will enable risk assessments, future threat evaluations, outbreak management and interventions to reduce disease burden.",2014 Apr 9,"['Nichols, Gordon L.', 'Andersson, Yvonne', 'Lindgren, Elisabet', 'Devaux, Isabelle', 'Semenza, Jan C.']",Int J Environ Res Public Health,,,True
35d7e6d1717c9b8604c8370ffdf26ea9569aa75d,PMC,Influenza A Virus Encoding Secreted Gaussia Luciferase as Useful Tool to Analyze Viral Replication and Its Inhibition by Antiviral Compounds and Cellular Proteins,http://dx.doi.org/10.1371/journal.pone.0097695,PMC4026478,24842154,CC BY,"Reporter genes inserted into viral genomes enable the easy and rapid quantification of virus replication, which is instrumental to efficient in vitro screening of antiviral compounds or in vivo analysis of viral spread and pathogenesis. Based on a published design, we have generated several replication competent influenza A viruses carrying either fluorescent proteins or Gaussia luciferase. Reporter activity could be readily quantified in infected cultures, but the virus encoding Gaussia luciferase was more stable than viruses bearing fluorescent proteins and was therefore analyzed in detail. Quantification of Gaussia luciferase activity in the supernatants of infected culture allowed the convenient and highly sensitive detection of viral spread, and enzymatic activity correlated with the number of infectious particles released from infected cells. Furthermore, the Gaussia luciferase encoding virus allowed the sensitive quantification of the antiviral activity of the neuraminidase inhibitor (NAI) zanamivir and the host cell interferon-inducible transmembrane (IFITM) proteins 1–3, which are known to inhibit influenza virus entry. Finally, the virus was used to demonstrate that influenza A virus infection is sensitive to a modulator of endosomal cholesterol, in keeping with the concept that IFITMs inhibit viral entry by altering cholesterol levels in the endosomal membrane. In sum, we report the characterization of a novel influenza A reporter virus, which allows fast and sensitive detection of viral spread and its inhibition, and we show that influenza A virus entry is sensitive to alterations of endosomal cholesterol levels.",2014 May 19,"['Eckert, Nadine', 'Wrensch, Florian', 'Gärtner, Sabine', 'Palanisamy, Navaneethan', 'Goedecke, Ulrike', 'Jäger, Nils', 'Pöhlmann, Stefan', 'Winkler, Michael']",PLoS One,,,True
6081206484e5e671f9a73195a8b1fac39e456a3e,PMC,Ethical Alternatives to Experiments with Novel Potential Pandemic Pathogens,http://dx.doi.org/10.1371/journal.pmed.1001646,PMC4028196,24844931,CC BY,Please see later in the article for the Editors' Summary,2014 May 20,"['Lipsitch, Marc', 'Galvani, Alison P.']",PLoS Med,,,True
a80b756097aea945ba90510f7fa55cc84f849686,PMC,Effect of Chicken Egg Yolk Antibodies (IgY) against Diarrhea in Domesticated Animals: A Systematic Review and Meta-Analysis,http://dx.doi.org/10.1371/journal.pone.0097716,PMC4028221,24846286,CC BY,"BACKGROUND: IgY antibodies are serum immunoglobulin in birds, reptiles and amphibians, and are transferred from serum to egg yolk to confer passive immunity to their embryos and offspring. Currently, the oral passive immunization using chicken IgY has been focused as an alternative to antibiotics for the treatment and control of diarrhea in animals and humans. This systematic review was focused to determine the effect of IgY in controlling and preventing diarrhea in domesticated animals including Piglets, Mice, Poultry and Calves. METHODS AND RESULTS: Previous research reports focused on treatment effect of Chicken IgY against diarrhea were retrieved from different electronic data bases (MEDLINE, EMBASE, SPRINGER-LINK, WILEY, AGRICOLA, MEDWELL Journals, Scientific Publish, Chinese articles from Core periodicals in 2012). A total of 61 studies in 4 different animal classes met the inclusion criteria. Data on study characteristics and outcome measures were extracted. The pooled relative risk (RR) of 49 studies of different animals [Piglets – 22; Mice – 14; Poultry – 7 and Calves – 6] in meta-analyses revealed that, IgY significantly reduced the risk of diarrhea in treatment group when compare to the placebo. However, the 95% confidence intervals of the majority of studies in animal class piglets and calves embrace RR of one. The same results were obtained in sub group analyses (treatment regiment – prophylactic or therapeutic; pathogen type – bacterial or viral). Perhaps, this inconsistency in the effect of IgY at the individual study level and overall effect measures could be influenced by the methodological heterogeneity. CONCLUSION: The present systematic review (SR) and meta-analysis demonstrated the beneficial effect of IgY. This supports the opinion that IgY is useful for prophylaxis and treatment. However, more intensive studies using the gold standard animal experiments with the focus to use IgY alone or in combination with other alternative strategies are indispensable.",2014 May 20,"['Diraviyam, Thirumalai', 'Zhao, Bin', 'Wang, Yuan', 'Schade, Ruediger', 'Michael, Antonysamy', 'Zhang, Xiaoying']",PLoS One,,,True
d31c8c30c1aaad525d6a1714296376a091414e5e,PMC,Trends in influenza vaccination coverage in Portugal from 1998 to 2010: effect of major pandemic threats,http://dx.doi.org/10.1186/1471-2458-13-1130,PMC4028814,24314008,CC BY,"BACKGROUND: Vaccination is the key measure available for prevention of the public health burden of annual influenza epidemics. This article describes national trends in seasonal influenza vaccine (IV) coverage in Portugal from 1998/99 to 2010/11, analyzes progress towards meeting WHO 2010 coverage goals, and addresses the effect of major public health threats of the last 12 years (SARS in 2003/04, influenza A (H5N1) in 2005/06, and the influenza A (H1N1)2009 pandemic) on vaccination trends. METHODS: The National Institute of Health surveyed (12 times) a random sample of Portuguese families. IV coverage was estimated and was adjusted for age distribution and country region. Independence of age and sex coverage distribution was tested using a modified F-statistic with a 5% significance level. The effect of SARS, A (H5N1), and the A (H1N1)2009 pandemic was tested using a meta-regression model. The model was adjusted for IV coverage in the general population and in the age groups. RESULTS: Between 1998/99 and 2010/11 IV, coverage in the general population varied between 14.2% (CI (95%): 11.6%–16.8%) and 17.5% (CI (95%): 17.6%–21.6%). There was no trend in coverage (p = 0.097). In the younger age group (<15 years) a declining trend was identified until 2008/09 (p = 0.005). This trend reversed in 2009/10. There was also a gradual and significant increase in seasonal IV coverage in the elderly (p for trend < 0.001). After 2006/07, IV coverage remained near 50%. Adjusting for baseline trends, there was significantly higher coverage in the general population in 2003/04 (p = 0.032) and 2005/06 (p = 0.018). The high coverage observed in the <15-year age group in season 2009/10 was also significant (p = 0.015). CONCLUSIONS: IV coverage in the elderly population displayed an increasing trend, but the 75% WHO 2010 target was not met. This result indicates that influenza vaccination strategy should be improved to meet the ambitious WHO coverage goals. The major pandemic threats of the past decade had a modest but significant effect on seasonal influenza vaccination. There was an increase in vaccine uptake proportion in the general population in 2003/04 and in 2005/06, and in individuals <15 years old in 2009/10.",2013 Dec 5,"['Pinto, Cátia Sousa', 'Nunes, Baltazar', 'Branco, Maria João', 'Falcão, José Marinho']",BMC Public Health,,,True
ab8da309a4060c4f4a3774c3ec9e7ebdc5a3a74e,PMC,α4-integrins control viral meningoencephalitis through differential recruitment of T helper cell subsets,http://dx.doi.org/10.1186/2051-5960-2-27,PMC4029267,24606807,CC BY,"INTRODUCTION: Natalizumab blocks α4-integrins and is a prototypic agent for a series of anti-inflammatory drugs that impair trafficking of immune cells into the CNS. However, modulation of the access of immune cells to the CNS is associated with impaired immune surveillance and detrimental viral infections of the CNS. Here, we explored the potency of cellular immune responses within the CNS to protect against viral encephalitis in mice with T cell conditional disruption of VLA-4 integrin (α4β1) expression. RESULTS: While VLA-4 expression in virus specific Th1 cells is non-redundant for their ability to access the CNS, α4-integrin deficient Th17 cells enter the CNS compartment and generate an inflammatory milieu upon intrathecal vaccinia virus (VV) infection. However, in contrast to Th1 cells that can adopt direct cytotoxic properties, Th17 cells fail to clear the virus due to insufficient Eomes induced perforin-1 expression. CONCLUSION: The quality of the intrathecal cellular antiviral response under conditions of impaired VLA-4 function jeopardizes host protection. Our functional in vivo data extend our mechanistic understanding of anti-viral immunity in the CNS and help to estimate the risk potential of upcoming therapeutic agents that target the trafficking of immune cells into distinct anatomical compartments.",2014 Mar 7,"['Rothhammer, Veit', 'Muschaweckh, Andreas', 'Gasteiger, Georg', 'Petermann, Franziska', 'Heink, Sylvia', 'Busch, Dirk H', 'Heikenwälder, Mathias', 'Hemmer, Bernhard', 'Drexler, Ingo', 'Korn, Thomas']",Acta Neuropathol Commun,,,True
36def2d37441d9ab0833ba1a1a48c68184bae246,PMC,Viral metagenomic analysis of feces of wild small carnivores,http://dx.doi.org/10.1186/1743-422X-11-89,PMC4030737,24886057,CC BY,"BACKGROUND: Recent studies have clearly demonstrated the enormous virus diversity that exists among wild animals. This exemplifies the required expansion of our knowledge of the virus diversity present in wildlife, as well as the potential transmission of these viruses to domestic animals or humans. METHODS: In the present study we evaluated the viral diversity of fecal samples (n = 42) collected from 10 different species of wild small carnivores inhabiting the northern part of Spain using random PCR in combination with next-generation sequencing. Samples were collected from American mink (Neovison vison), European mink (Mustela lutreola), European polecat (Mustela putorius), European pine marten (Martes martes), stone marten (Martes foina), Eurasian otter (Lutra lutra) and Eurasian badger (Meles meles) of the family of Mustelidae; common genet (Genetta genetta) of the family of Viverridae; red fox (Vulpes vulpes) of the family of Canidae and European wild cat (Felis silvestris) of the family of Felidae. RESULTS: A number of sequences of possible novel viruses or virus variants were detected, including a theilovirus, phleboviruses, an amdovirus, a kobuvirus and picobirnaviruses. CONCLUSIONS: Using random PCR in combination with next generation sequencing, sequences of various novel viruses or virus variants were detected in fecal samples collected from Spanish carnivores. Detected novel viruses highlight the viral diversity that is present in fecal material of wild carnivores.",2014 May 15,"['Bodewes, Rogier', 'Ruiz-Gonzalez, Aritz', 'Schapendonk, Claudia ME', 'van den Brand, Judith MA', 'Osterhaus, Albert DME', 'Smits, Saskia L']",Virol J,,,True
2bf9a03995b1056dc5d3e353461d3a31a9348885,PMC,Molecular Insights into Poly(ADP-ribose) Recognition and Processing,http://dx.doi.org/10.3390/biom3010001,PMC4030884,24970154,CC BY,"Poly(ADP-ribosyl)ation is a post-translational protein modification involved in the regulation of important cellular functions including DNA repair, transcription, mitosis and apoptosis. The amount of poly(ADP-ribosyl)ation (PAR) in cells reflects the balance of synthesis, mediated by the PARP protein family, and degradation, which is catalyzed by a glycohydrolase, PARG. Many of the proteins mediating PAR metabolism possess specialised high affinity PAR-binding modules that allow the efficient sensing or processing of the PAR signal. The identification of four such PAR-binding modules and the characterization of a number of proteins utilising these elements during the last decade has provided important insights into how PAR regulates different cellular activities. The macrodomain represents a unique PAR-binding module which is, in some instances, known to possess enzymatic activity on ADP-ribose derivatives (in addition to PAR-binding). The most recently discovered example for this is the PARG protein, and several available PARG structures have provided an understanding into how the PARG macrodomain evolved into a major enzyme that maintains PAR homeostasis in living cells.",2012 Dec 21,"['Žaja, Roko', 'Mikoč, Andreja', 'Barkauskaite, Eva', 'Ahel, Ivan']",Biomolecules,,,True
cfdfb727440e1010a4189d0c9bee58330c0383dc,PMC,The 3′-Terminal 55 Nucleotides of Bovine Coronavirus Defective Interfering RNA Harbor Cis-Acting Elements Required for Both Negative- and Positive-Strand RNA Synthesis,http://dx.doi.org/10.1371/journal.pone.0098422,PMC4031142,24852421,CC BY,"The synthesis of the negative-strand [(−)-strand] complement of the ∼30 kilobase, positive-strand [(+)-strand] coronaviral genome is a necessary early step for genome replication. The identification of cis-acting elements required for (−)-strand RNA synthesis in coronaviruses, however, has been hampered due to insufficiencies in the techniques used to detect the (−)-strand RNA species. Here, we employed a method of head-to-tail ligation and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) to detect and quantitate the synthesis of bovine coronavirus (BCoV) defective interfering (DI) RNA (−) strands. Furthermore, using the aforementioned techniques along with Northern blot assay, we specifically defined the cis-acting RNA elements within the 3′-terminal 55 nucleotides (nts) which function in the synthesis of (−)- or (+)-strand BCoV DI RNA. The major findings are as follows: (i) nts from -5 to -39 within the 3′-terminal 55 nts are the cis-acting elements responsible for (−)-strand BCoV DI RNA synthesis, (ii) nts from −3 to −34 within the 3′-terminal 55 nts are cis-acting elements required for (+)-strand BCoV DI RNA synthesis, and (iii) the nucleotide species at the 3′-most position (−1) is important, but not critical, for both (−)- and (+)-strand BCoV DI RNA synthesis. These results demonstrate that the 3′-terminal 55 nts in BCoV DI RNA harbor cis-acting RNA elements required for both (−)- and (+)-strand DI RNA synthesis and extend our knowledge on the mechanisms of coronavirus replication. The method of head-to-tail ligation and qRT-PCR employed in the study may also be applied to identify other cis-acting elements required for (−)-strand RNA synthesis in coronaviruses.",2014 May 22,"['Liao, Wei-Yu', 'Ke, Ting-Yung', 'Wu, Hung-Yi']",PLoS One,,,True
bc1beba35495c40001df667b4612b7cb9bb67185,PMC,One Health: Past Successes and Future Challenges in Three African Contexts,http://dx.doi.org/10.1371/journal.pntd.0002884,PMC4031173,24851901,CC BY,"BACKGROUND: The recent emergence of zoonotic diseases such as Highly Pathogenic Avian Influenza (HPAI) and Severe Acute Respiratory Syndrome (SARS) have contributed to dominant Global Health narratives around health securitisation and pandemic preparedness, calling for greater co-operation between the health, veterinary and environmental sectors in the ever-evolving One Health movement. A decade later, One Health advocates face increasing pressure to translate the approach from theory into action. METHODOLOGY/PRINCIPAL FINDINGS: A qualitative case study methodology was used to examine the emerging relationships between international One Health dialogue and its practical implementation in the African health policy context. A series of Key Informant Interviews (n = 32) with policy makers, government officials and academics in Nigeria, Tanzania and Uganda are presented as three separate case studies. Each case examines a significant aspect of One Health operationalisation, framed around the control of both emerging and Neglected Zoonotic Diseases including HPAI, Human African Trypanosomiasis and rabies. The research found that while there is general enthusiasm and a strong affirmative argument for adoption of One Health approaches in Africa, identifying alternative contexts away from a narrow focus on pandemics will help broaden its appeal, particularly for national or regionally significant endemic and neglected diseases not usually addressed under a “global” remit. CONCLUSIONS/SIGNIFICANCE: There is no ‘one size fits all’ approach to achieving the intersectoral collaboration, significant resource mobilisation and political co-operation required to realise a One Health approach. Individual country requirements cannot be underestimated, dismissed or prescribed in a top down manner. This article contributes to the growing discussion regarding not whether One Health should be operationalised, but how this may be achieved.",2014 May 22,"['Okello, Anna L.', 'Bardosh, Kevin', 'Smith, James', 'Welburn, Susan C.']",PLoS Negl Trop Dis,,,True
b7b6bf20c919a0b200c528e76f76f508d5554700,PMC,Structural Basis for the Ubiquitin-Linkage Specificity and deISGylating Activity of SARS-CoV Papain-Like Protease,http://dx.doi.org/10.1371/journal.ppat.1004113,PMC4031219,24854014,CC BY,"Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes a papain-like protease (PLpro) with both deubiquitinating (DUB) and deISGylating activities that are proposed to counteract the post-translational modification of signaling molecules that activate the innate immune response. Here we examine the structural basis for PLpro's ubiquitin chain and interferon stimulated gene 15 (ISG15) specificity. We present the X-ray crystal structure of PLpro in complex with ubiquitin-aldehyde and model the interaction of PLpro with other ubiquitin-chain and ISG15 substrates. We show that PLpro greatly prefers K48- to K63-linked ubiquitin chains, and ISG15-based substrates to those that are mono-ubiquitinated. We propose that PLpro's higher affinity for K48-linked ubiquitin chains and ISG15 stems from a bivalent mechanism of binding, where two ubiquitin-like domains prefer to bind in the palm domain of PLpro with the most distal ubiquitin domain interacting with a “ridge” region of the thumb domain. Mutagenesis of residues within this ridge region revealed that these mutants retain viral protease activity and the ability to catalyze hydrolysis of mono-ubiquitin. However, a select number of these mutants have a significantly reduced ability to hydrolyze the substrate ISG15-AMC, or be inhibited by K48-linked diubuiquitin. For these latter residues, we found that PLpro antagonism of the nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB) signaling pathway is abrogated. This identification of key and unique sites in PLpro required for recognition and processing of diubiquitin and ISG15 versus mono-ubiquitin and protease activity provides new insight into ubiquitin-chain and ISG15 recognition and highlights a role for PLpro DUB and deISGylase activity in antagonism of the innate immune response.",2014 May 22,"['Ratia, Kiira', 'Kilianski, Andrew', 'Baez-Santos, Yahira M.', 'Baker, Susan C.', 'Mesecar, Andrew']",PLoS Pathog,,,True
2074bedae293a25ea9023dc8802bd67b3a626b83,PMC,Structural Basis for the Ubiquitin-Linkage Specificity and deISGylating Activity of SARS-CoV Papain-Like Protease,http://dx.doi.org/10.1371/journal.ppat.1004113,PMC4031219,24854014,CC BY,"Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes a papain-like protease (PLpro) with both deubiquitinating (DUB) and deISGylating activities that are proposed to counteract the post-translational modification of signaling molecules that activate the innate immune response. Here we examine the structural basis for PLpro's ubiquitin chain and interferon stimulated gene 15 (ISG15) specificity. We present the X-ray crystal structure of PLpro in complex with ubiquitin-aldehyde and model the interaction of PLpro with other ubiquitin-chain and ISG15 substrates. We show that PLpro greatly prefers K48- to K63-linked ubiquitin chains, and ISG15-based substrates to those that are mono-ubiquitinated. We propose that PLpro's higher affinity for K48-linked ubiquitin chains and ISG15 stems from a bivalent mechanism of binding, where two ubiquitin-like domains prefer to bind in the palm domain of PLpro with the most distal ubiquitin domain interacting with a “ridge” region of the thumb domain. Mutagenesis of residues within this ridge region revealed that these mutants retain viral protease activity and the ability to catalyze hydrolysis of mono-ubiquitin. However, a select number of these mutants have a significantly reduced ability to hydrolyze the substrate ISG15-AMC, or be inhibited by K48-linked diubuiquitin. For these latter residues, we found that PLpro antagonism of the nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB) signaling pathway is abrogated. This identification of key and unique sites in PLpro required for recognition and processing of diubiquitin and ISG15 versus mono-ubiquitin and protease activity provides new insight into ubiquitin-chain and ISG15 recognition and highlights a role for PLpro DUB and deISGylase activity in antagonism of the innate immune response.",2014 May 22,"['Ratia, Kiira', 'Kilianski, Andrew', 'Baez-Santos, Yahira M.', 'Baker, Susan C.', 'Mesecar, Andrew']",PLoS Pathog,,,False
18adcbf84b2bc81951a30bad117fc8d0a3cc623e,PMC,Structural Basis for the Ubiquitin-Linkage Specificity and deISGylating Activity of SARS-CoV Papain-Like Protease,http://dx.doi.org/10.1371/journal.ppat.1004113,PMC4031219,24854014,CC BY,"Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes a papain-like protease (PLpro) with both deubiquitinating (DUB) and deISGylating activities that are proposed to counteract the post-translational modification of signaling molecules that activate the innate immune response. Here we examine the structural basis for PLpro's ubiquitin chain and interferon stimulated gene 15 (ISG15) specificity. We present the X-ray crystal structure of PLpro in complex with ubiquitin-aldehyde and model the interaction of PLpro with other ubiquitin-chain and ISG15 substrates. We show that PLpro greatly prefers K48- to K63-linked ubiquitin chains, and ISG15-based substrates to those that are mono-ubiquitinated. We propose that PLpro's higher affinity for K48-linked ubiquitin chains and ISG15 stems from a bivalent mechanism of binding, where two ubiquitin-like domains prefer to bind in the palm domain of PLpro with the most distal ubiquitin domain interacting with a “ridge” region of the thumb domain. Mutagenesis of residues within this ridge region revealed that these mutants retain viral protease activity and the ability to catalyze hydrolysis of mono-ubiquitin. However, a select number of these mutants have a significantly reduced ability to hydrolyze the substrate ISG15-AMC, or be inhibited by K48-linked diubuiquitin. For these latter residues, we found that PLpro antagonism of the nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB) signaling pathway is abrogated. This identification of key and unique sites in PLpro required for recognition and processing of diubiquitin and ISG15 versus mono-ubiquitin and protease activity provides new insight into ubiquitin-chain and ISG15 recognition and highlights a role for PLpro DUB and deISGylase activity in antagonism of the innate immune response.",2014 May 22,"['Ratia, Kiira', 'Kilianski, Andrew', 'Baez-Santos, Yahira M.', 'Baker, Susan C.', 'Mesecar, Andrew']",PLoS Pathog,,,False
4d968bbfddfa8eb4f1cad1f00ed121ec2c4a4df6,PMC,A new paradigm: innate immune sensing of viruses via the unfolded protein response,http://dx.doi.org/10.3389/fmicb.2014.00222,PMC4032990,24904537,CC BY,"The immune system depends upon combinations of signals to mount appropriate responses: pathogen specific signals in the context of co-stimulatory “danger” signals drive immune strength and accuracy. Viral infections trigger anti-viral type I interferon (IFN) responses by stimulating endosomal and cytosolic pattern recognition receptors (PRRs). However, viruses have also evolved many strategies to counteract IFN responses. Are there intracellular danger signals that enhance immune responses to viruses? During infection, viruses place a heavy demand on the protein folding machinery of the host endoplasmic reticulum (ER). To survive ER stress, host cells mount an unfolded protein response (UPR) to decrease ER protein load and enhance protein-folding capacity. Viruses also directly elicit the UPR to enhance their replication. Increasing evidence supports an intersection between the host UPR and inflammation, in particular the production of pro-inflammatory cytokines and type I IFN. The UPR directly activates pro-inflammatory cytokine transcription factors and dramatically enhances cytokine production in response to viral PRR engagement. Additionally, viral PRR engagement may stimulate specific pathways within the UPR to enhance cytokine production. Through these mechanisms, viral detection via the UPR and inflammatory cytokine production are intertwined. Consequently, the UPR response is perfectly poised to act as an infection-triggered “danger” signal. The UPR may serve as an internal “co-stimulatory” signal that (1) provides specificity and (2) critically augments responses to overcome viral subterfuge. Further work is needed to test this hypothesis during viral infections.",2014 May 16,"Smith, Judith A.",Front Microbiol,,,True
78b3f2e613d0e2be8608c68c73b20c25d440a0b8,PMC,Unfolded protein response in hepatitis C virus infection,http://dx.doi.org/10.3389/fmicb.2014.00233,PMC4033015,24904547,CC BY,"Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus of clinical importance. The virus establishes a chronic infection and can progress from chronic hepatitis, steatosis to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The mechanisms of viral persistence and pathogenesis are poorly understood. Recently the unfolded protein response (UPR), a cellular homeostatic response to endoplasmic reticulum (ER) stress, has emerged to be a major contributing factor in many human diseases. It is also evident that viruses interact with the host UPR in many different ways and the outcome could be pro-viral, anti-viral or pathogenic, depending on the particular type of infection. Here we present evidence for the elicitation of chronic ER stress in HCV infection. We analyze the UPR signaling pathways involved in HCV infection, the various levels of UPR regulation by different viral proteins and finally, we propose several mechanisms by which the virus provokes the UPR.",2014 May 20,"Chan, Shiu-Wan",Front Microbiol,,,True
488e1294b604a8ea66aa4f21f431b52723dfc8de,PMC,"Enterovirus 71 related severe hand, foot and mouth disease outbreaks in South-East Asia: current situation and ongoing challenges",http://dx.doi.org/10.1136/jech-2014-203836,PMC4033151,24652348,CC BY,,2014 Jun 20,"['Sabanathan, Saraswathy', 'Tan, Le Van', 'Thwaites, Louise', 'Wills, Bridget', 'Qui, Phan Tu', 'Rogier van Doorn, H']",J Epidemiol Community Health,,,True
6b3f7521b0b4ed6a0230e0ce6ab2f4c02892a287,PMC,Epidemiology of virus-induced asthma exacerbations: with special reference to the role of human rhinovirus,http://dx.doi.org/10.3389/fmicb.2014.00226,PMC4033317,24904541,CC BY,"Viral respiratory infections may be associated with the virus-induced asthma in adults as well as children. Particularly, human rhinovirus is strongly suggested a major candidate for the associations of the virus-induced asthma. Thus, in this review, we reviewed and focused on the epidemiology, pathophysiology, and treatment of virus-induced asthma with special reference on human rhinovirus. Furthermore, we added our preliminary data regarding the clinical and virological findings in the present review.",2014 May 26,"['Saraya, Takeshi', 'Kurai, Daisuke', 'Ishii, Haruyuki', 'Ito, Anri', 'Sasaki, Yoshiko', 'Niwa, Shoichi', 'Kiyota, Naoko', 'Tsukagoshi, Hiroyuki', 'Kozawa, Kunihisa', 'Goto, Hajime', 'Takizawa, Hajime']",Front Microbiol,,,True
cbc8e184157e7543e44f09f2be3999131db359e2,PMC,Comparative Analysis of Lycorine in Wild Plant and Callus Culture Samples of Hymenocallis littoralis by HPLC-UV Method,http://dx.doi.org/10.1155/2014/408306,PMC4033353,24895650,CC BY,"The Hymenocallis littoralis, an ornamental and medicinal plant, had been traditionally used for wound healing. In the present study, an analytical method using HPLC with ultraviolet detection was developed for the quantification of lycorine in the extracts of different parts of wild plant and tissue culture samples of H. littoralis. The separation was achieved using a reversed-phase column. The method was found to be accurate, repeatable, and sensitive for the quantification of minute amount of lycorine present in the samples. The highest lycorine content was found in the bulb extract (2.54 ± 0.02 μg/mg) whereas the least was in the root extract (0.71 ± 0.02 μg/mg) of the wild plants. Few callus culture samples had high content of lycorine, comparable to that of wild plants. The results showed that plant growth regulators, 2,4-dichlorophenoxyacetic acid (2,4-D) alone at 4.5 μM (2.58 ± 0.38 μg/mg) or a combination of 2,4-D at 9.00 μM with 4.5 μM of 6-benzylaminopurine (BAP), were the optimum concentrations for the production of high lycorine (2.45 ± 0.15 μg/mg) content in callus culture. The present analytical method could be of value for routine quantification of lycorine in the tissue culture production and standardization of the raw material or extracts of H. littoralis.",2014 May 6,"['Subramaniam, Sreeramanan', 'Sundarasekar, Jeevandran', 'Sahgal, Geethaa', 'Murugaiyah, Vikneswaran']",ScientificWorldJournal,,,True
d0a6596fcbf8b76491fd4f2c4da8d9037170caf8,PMC,Cellular unfolded protein response against viruses used in gene therapy,http://dx.doi.org/10.3389/fmicb.2014.00250,PMC4033601,24904562,CC BY,"Viruses are excellent vehicles for gene therapy due to their natural ability to infect and deliver the cargo to specific tissues with high efficiency. Although such vectors are usually “gutted” and are replication defective, they are subjected to clearance by the host cells by immune recognition and destruction. Unfolded protein response (UPR) is a naturally evolved cyto-protective signaling pathway which is triggered due to endoplasmic reticulum (ER) stress caused by accumulation of unfolded/misfolded proteins in its lumen. The UPR signaling consists of three signaling pathways, namely PKR-like ER kinase, activating transcription factor 6, and inositol-requiring protein-1. Once activated, UPR triggers the production of ER molecular chaperones and stress response proteins to help reduce the protein load within the ER. This occurs by degradation of the misfolded proteins and ensues in the arrest of protein translation machinery. If the burden of protein load in ER is beyond its processing capacity, UPR can activate pro-apoptotic pathways or autophagy leading to cell death. Viruses are naturally evolved in hijacking the host cellular translation machinery to generate a large amount of proteins. This phenomenon disrupts ER homeostasis and leads to ER stress. Alternatively, in the case of gutted vectors used in gene therapy, the excess load of recombinant vectors administered and encountered by the cell can trigger UPR. Thus, in the context of gene therapy, UPR becomes a major roadblock that can potentially trigger inflammatory responses against the vectors and reduce the efficiency of gene transfer.",2014 May 26,"['Sen, Dwaipayan', 'Balakrishnan, Balaji', 'Jayandharan, Giridhara R.']",Front Microbiol,,,True
46c2eb2186aa09c3963227ce0195a881ac26de7d,PMC,Cell-Penetrating Peptides for Antiviral Drug Development,http://dx.doi.org/10.3390/ph3030448,PMC4033964,27713263,CC BY,"Viral diseases affect hundreds of millions of people worldwide, and the few available drugs to treat these diseases often come with limitations. The key obstacle to the development of new antiviral agents is their delivery into infected cells in vivo. Cell-penetrating peptides (CPPs) are short peptides that can cross the cellular lipid bilayer with the remarkable capability to shuttle conjugated cargoes into cells. CPPs have been successfully utilized to enhance the cellular uptake and intracellular trafficking of antiviral molecules, and thereby increase the inhibitory activity of potential antiviral proteins and oligonucleotide analogues, both in cultured cells and in animal models. This review will address the notable findings of these studies, highlighting some promising results and discussing the challenges CPP technology has to overcome for further clinical applications.",2010 Mar 2,"['Delcroix, Melaine', 'Riley, Lee W.']",Pharmaceuticals (Basel),,,True
b94bee4f159369de60f7d9e7cc5733676dfa15b8,PMC,Building Cell Selectivity into CPP-Mediated Strategies,http://dx.doi.org/10.3390/ph3051456,PMC4033992,27713313,CC BY,"There is a pressing need for more effective and selective therapies for cancer and other diseases. Consequently, much effort is being devoted to the development of alternative experimental approaches based on selective systems, which are designed to be specifically directed against target cells. In addition, a large number of highly potent therapeutic molecules are being discovered. However, they do not reach clinical trials because of their low delivery, poor specificity or their incapacity to bypass the plasma membrane. Cell-penetrating peptides (CPPs) are an open door for cell-impermeable compounds to reach intracellular targets. Putting all these together, research is sailing in the direction of the design of systems with the capacity to transport new drugs into a target cell. Some CPPs show cell type specificity while others require modifications or form part of more sophisticated drug delivery systems. In this review article we summarize several strategies for directed drug delivery involving CPPs that have been reported in the literature.",2010 May 14,"['Martín, Irene', 'Teixidó, Meritxell', 'Giralt, Ernest']",Pharmaceuticals (Basel),,,True
8446bfae882d6ec192e572e9bbcb858eeae83cc8,PMC,DV-Curve Representation of Protein Sequences and Its Application,http://dx.doi.org/10.1155/2014/203871,PMC4034481,24899916,CC BY,"Based on the detailed hydrophobic-hydrophilic(HP) model of amino acids, we propose dual-vector curve (DV-curve) representation of protein sequences, which uses two vectors to represent one alphabet of protein sequences. This graphical representation not only avoids degeneracy, but also has good visualization no matter how long these sequences are, and can reflect the length of protein sequence. Then we transform the 2D-graphical representation into a numerical characterization that can facilitate quantitative comparison of protein sequences. The utility of this approach is illustrated by two examples: one is similarity/dissimilarity comparison among different ND6 protein sequences based on their DV-curve figures the other is the phylogenetic analysis among coronaviruses based on their spike proteins.",2014 May 8,"['Deng, Wei', 'Luan, Yihui']",Comput Math Methods Med,,,True
33222702ba2e2e7e5f526c667d64beb5bd2cda96,PMC,Improving the estimation of the death rate of infected cells from time course data during the acute phase of virus infections: application to acute HIV-1 infection in a humanized mouse model,http://dx.doi.org/10.1186/1742-4682-11-22,PMC4035760,24885827,CC BY,"BACKGROUND: Mathematical modeling of virus dynamics has provided quantitative insights into viral infections such as influenza, the simian immunodeficiency virus/human immunodeficiency virus, hepatitis B, and hepatitis C. Through modeling, we can estimate the half-life of infected cells, the exponential growth rate, and the basic reproduction number (R(0)). To calculate R(0) from virus load data, the death rate of productively infected cells is required. This can be readily estimated from treatment data collected during the chronic phase, but is difficult to determine from acute infection data. Here, we propose two new models that can reliably estimate the average life span of infected cells from acute-phase data, and apply both methods to experimental data from humanized mice infected with HIV-1. METHODS: Both new models, called as the reduced quasi-steady state (RQS) model and the piece-wise regression (PWR) model, are derived by simplification of a standard model for the acute-phase dynamics of target cells, viruses and infected cells. By having only a limited number of parameters, both models allow us to reliably estimate the death rate of productively infected cells. Simulated datasets with plausible parameter values are generated with the standard model to compare the performance of the new models with that of the major previous model (i.e., the simple exponential model). Finally, we fit models to time course data from HIV-1 infected humanized mice to estimate the several important parameters characterizing their acute infection. RESULTS AND CONCLUSIONS: The new models provided much better estimates than the previous model because they more precisely capture the de novo infection process. Both models describe the acute phase of HIV-1 infected humanized mice reasonably well, and we estimated an average death rate of infected cells of 0.61 and 0.61, an average exponential growth rate of 0.69 and 0.76, and an average basic reproduction number of 2.30 and 2.38 in the RQS model and the PWR model, respectively. These estimates are fairly close to those obtained in humans.",2014 May 21,"['Ikeda, Hiroki', 'de Boer, Rob J', 'Sato, Kei', 'Morita, Satoru', 'Misawa, Naoko', 'Koyanagi, Yoshio', 'Aihara, Kazuyuki', 'Iwami, Shingo']",Theor Biol Med Model,,,True
d33a044bbb52673f1eeeb792b0376b0987fe02f6,PMC,Evaluation of the Broad-Range PCR-Electrospray Ionization Mass Spectrometry (PCR/ESI-MS) System and Virus Microarrays for Virus Detection,http://dx.doi.org/10.3390/v6051876,PMC4036539,24777034,CC BY,"Advanced nucleic acid-based technologies are powerful research tools for novel virus discovery but need to be standardized for broader applications such as virus detection in biological products and clinical samples. We have used well-characterized retrovirus stocks to evaluate the limit of detection (LOD) for broad-range PCR with electrospray ionization mass spectrometry (PCR/ESI-MS or PLEX-ID), RT-PCR assays, and virus microarrays. The results indicated that in the absence of background cellular nucleic acids, PLEX-ID and RT-PCR had a similar LOD for xenotropic murine retrovirus-related virus (XMRV; 3.12 particles per µL) whereas sensitivity of virus detection was 10-fold greater using virus microarrays. When virus was spiked into a background of cellular nucleic acids, the LOD using PLEX-ID remained the same, whereas virus detection by RT-PCR was 10-fold less sensitive, and no virus could be detected by microarrays. Expected endogenous retrovirus (ERV) sequences were detected in cell lines tested and known species-specific viral sequences were detected in bovine serum and porcine trypsin. A follow-up strategy was developed using PCR amplification, nucleotide sequencing, and bioinformatics to demonstrate that an RD114-like retrovirus sequence that was detected by PLEX-ID in canine cell lines (Madin-Darby canine kidney (MDCK) and Cf2Th canine thymus) was due to defective, endogenous gammaretrovirus-related sequences.",2014 Apr 25,"['Taliaferro, Lanyn P.', 'Galvin, Teresa A.', 'Ma, Hailun', 'Shaheduzzaman, Syed', 'Williams, Dhanya K.', 'Glasner, Dustin R.', 'Khan, Arifa S.']",Viruses,,,True
baf2944b65112b4b45b0c0f6aeb16e3e90a4f61e,PMC,Hantavirus Reservoirs: Current Status with an Emphasis on Data from Brazil,http://dx.doi.org/10.3390/v6051929,PMC4036540,24784571,CC BY,"Since the recognition of hantavirus as the agent responsible for haemorrhagic fever in Eurasia in the 1970s and, 20 years later, the descovery of hantavirus pulmonary syndrome in the Americas, the genus Hantavirus has been continually described throughout the World in a variety of wild animals. The diversity of wild animals infected with hantaviruses has only recently come into focus as a result of expanded wildlife studies. The known reservoirs are more than 80, belonging to 51 species of rodents, 7 bats (order Chiroptera) and 20 shrews and moles (order Soricomorpha). More than 80genetically related viruses have been classified within Hantavirus genus; 25 recognized as human pathogens responsible for a large spectrum of diseases in the Old and New World. In Brazil, where the diversity of mammals and especially rodents is considered one of the largest in the world, 9 hantavirus genotypes have been identified in 12 rodent species belonging to the genus Akodon, Calomys, Holochilus, Oligoryzomys, Oxymycterus, Necromys and Rattus. Considering the increasing number of animals that have been implicated as reservoirs of different hantaviruses, the understanding of this diversity is important for evaluating the risk of distinct hantavirus species as human pathogens.",2014 Apr 29,"['Carvalho de Oliveira, Renata', 'Guterres, Alexandro', 'Fernandes, Jorlan', 'D’Andrea, Paulo Sérgio', 'Bonvicino, Cibele Rodrigues', 'de Lemos, Elba Regina Sampaio']",Viruses,,,True
50e19c5dc4c5f5934e19be3082fb5aca082870fb,PMC,Hantavirus Reservoirs: Current Status with an Emphasis on Data from Brazil,http://dx.doi.org/10.3390/v6051929,PMC4036540,24784571,CC BY,"Since the recognition of hantavirus as the agent responsible for haemorrhagic fever in Eurasia in the 1970s and, 20 years later, the descovery of hantavirus pulmonary syndrome in the Americas, the genus Hantavirus has been continually described throughout the World in a variety of wild animals. The diversity of wild animals infected with hantaviruses has only recently come into focus as a result of expanded wildlife studies. The known reservoirs are more than 80, belonging to 51 species of rodents, 7 bats (order Chiroptera) and 20 shrews and moles (order Soricomorpha). More than 80genetically related viruses have been classified within Hantavirus genus; 25 recognized as human pathogens responsible for a large spectrum of diseases in the Old and New World. In Brazil, where the diversity of mammals and especially rodents is considered one of the largest in the world, 9 hantavirus genotypes have been identified in 12 rodent species belonging to the genus Akodon, Calomys, Holochilus, Oligoryzomys, Oxymycterus, Necromys and Rattus. Considering the increasing number of animals that have been implicated as reservoirs of different hantaviruses, the understanding of this diversity is important for evaluating the risk of distinct hantavirus species as human pathogens.",2014 Apr 29,"['Carvalho de Oliveira, Renata', 'Guterres, Alexandro', 'Fernandes, Jorlan', 'D’Andrea, Paulo Sérgio', 'Bonvicino, Cibele Rodrigues', 'de Lemos, Elba Regina Sampaio']",Viruses,,,False
03148d1ba3c986ec7306ab2a90bcd6082c512f49,PMC,Evidence for Retrovirus and Paramyxovirus Infection of Multiple Bat Species in China,http://dx.doi.org/10.3390/v6052138,PMC4036550,24841387,CC BY,"Bats are recognized reservoirs for many emerging zoonotic viruses of public health importance. Identifying and cataloguing the viruses of bats is a logical approach to evaluate the range of potential zoonoses of bat origin. We characterized the fecal pathogen microbiome of both insectivorous and frugivorous bats, incorporating 281 individual bats comprising 20 common species, which were sampled in three locations of Yunnan province, by combining reverse transcription polymerase chain reaction (RT-PCR) assays and next-generation sequencing. Seven individual bats were paramyxovirus-positive by RT-PCR using degenerate primers, and these paramyxoviruses were mainly classified into three genera (Rubulavirus, Henipavirus and Jeilongvirus). Various additional novel pathogens were detected in the paramyxovirus-positive bats using Illumina sequencing. A total of 7066 assembled contigs (≥200 bp) were constructed, and 105 contigs matched eukaryotic viruses (of them 103 belong to 2 vertebrate virus families, 1 insect virus, and 1 mycovirus), 17 were parasites, and 4913 were homologous to prokaryotic microorganisms. Among the 103 vertebrate viral contigs, 79 displayed low identity (<70%) to known viruses including human viruses at the amino acid level, suggesting that these belong to novel and genetically divergent viruses. Overall, the most frequently identified viruses, particularly in bats from the family Hipposideridae, were retroviruses. The present study expands our understanding of the bat virome in species commonly found in Yunnan, China, and provides insight into the overall diversity of viruses that may be capable of directly or indirectly crossing over into humans.",2014 May 16,"['Yuan, Lihong', 'Li, Min', 'Li, Linmiao', 'Monagin, Corina', 'Chmura, Aleksei A.', 'Schneider, Bradley S.', 'Epstein, Jonathan H.', 'Mei, Xiaolin', 'Shi, Zhengli', 'Daszak, Peter', 'Chen, Jinping']",Viruses,,,True
247a9eae1e4452f7f969ab41a88f335fda54fbc9,PMC,Evidence for Retrovirus and Paramyxovirus Infection of Multiple Bat Species in China,http://dx.doi.org/10.3390/v6052138,PMC4036550,24841387,CC BY,"Bats are recognized reservoirs for many emerging zoonotic viruses of public health importance. Identifying and cataloguing the viruses of bats is a logical approach to evaluate the range of potential zoonoses of bat origin. We characterized the fecal pathogen microbiome of both insectivorous and frugivorous bats, incorporating 281 individual bats comprising 20 common species, which were sampled in three locations of Yunnan province, by combining reverse transcription polymerase chain reaction (RT-PCR) assays and next-generation sequencing. Seven individual bats were paramyxovirus-positive by RT-PCR using degenerate primers, and these paramyxoviruses were mainly classified into three genera (Rubulavirus, Henipavirus and Jeilongvirus). Various additional novel pathogens were detected in the paramyxovirus-positive bats using Illumina sequencing. A total of 7066 assembled contigs (≥200 bp) were constructed, and 105 contigs matched eukaryotic viruses (of them 103 belong to 2 vertebrate virus families, 1 insect virus, and 1 mycovirus), 17 were parasites, and 4913 were homologous to prokaryotic microorganisms. Among the 103 vertebrate viral contigs, 79 displayed low identity (<70%) to known viruses including human viruses at the amino acid level, suggesting that these belong to novel and genetically divergent viruses. Overall, the most frequently identified viruses, particularly in bats from the family Hipposideridae, were retroviruses. The present study expands our understanding of the bat virome in species commonly found in Yunnan, China, and provides insight into the overall diversity of viruses that may be capable of directly or indirectly crossing over into humans.",2014 May 16,"['Yuan, Lihong', 'Li, Min', 'Li, Linmiao', 'Monagin, Corina', 'Chmura, Aleksei A.', 'Schneider, Bradley S.', 'Epstein, Jonathan H.', 'Mei, Xiaolin', 'Shi, Zhengli', 'Daszak, Peter', 'Chen, Jinping']",Viruses,,,True
b53f3fa13a84fed43c6314ae35e98f59eb54c9e9,PMC,On-farm biosecurity as perceived by professionals visiting Swedish farms,http://dx.doi.org/10.1186/1751-0147-56-28,PMC4036743,24886408,CC BY,"BACKGROUND: On-farm biosecurity is an important part of disease prevention and control, this applies to live animal contacts as well as indirect contacts e.g. via professionals visiting farms in their work. The objectives of this study were to investigate how professionals visiting animal farms in Sweden in their daily work perceive the on-farm conditions for biosecurity, the factors that influence their own biosecurity routines and what they describe as obstacles for biosecurity. Suggestions for improvements were also asked for. Questionnaires were distributed to professionals visiting farms in their daily work; veterinarians, livestock hauliers, artificial insemination technicians, animal welfare inspectors and cattle hoof trimmers. The sample was a convenience sample, based on accessibility to registers or collaboration with organisations distributing the questionnaire. Respondents were asked about the availability of certain biosecurity conditions related to farm visits, e.g. if facilities for hand washing were available, how important different factors were for their own routines and, through open ended questions, to describe obstacles and suggestions for improvement. RESULTS: After data cleaning, there were responses from 368 persons. There was a difference in the proportion of visited farms reported to have certain biosecurity measures in place related to animal species present on the farm. In general, visited pig farms had a higher proportion of biosecurity measures in place, whereas the conditions were poorer on sheep and goat farms and horse farms. There were also differences between the visitor categories; the perceived conditions for biosecurity varied between the groups, e.g. livestock hauliers did not have access to hand washing facilities as often as veterinarians did. In all groups, a majority of the respondents perceived obstacles for on-farm biosecurity, among veterinarians 66% perceived that there were obstacles. Many of the reported obstacles related to the very basics of biosecurity, such as access to soap and water. Responsibility was identified to be a key issue; while some farmers expect visitors to take responsibility for keeping up biosecurity they do not provide the adequate on-farm conditions. CONCLUSIONS: Many of the respondents reported obstacles for keeping good biosecurity related to on-farm conditions. There was a gap when it came to responsibility which needs to be clarified. Visitors need to take responsibility for avoiding spread of disease, while farmers need to assume responsibility for providing adequate conditions for on-farm biosecurity.",2014 May 9,"['Nöremark, Maria', 'Sternberg-Lewerin, Susanna']",Acta Vet Scand,,,True
b1926f529e31d88fd6796fdae1916ced6d609c44,PMC,On-farm biosecurity as perceived by professionals visiting Swedish farms,http://dx.doi.org/10.1186/1751-0147-56-28,PMC4036743,24886408,CC BY,"BACKGROUND: On-farm biosecurity is an important part of disease prevention and control, this applies to live animal contacts as well as indirect contacts e.g. via professionals visiting farms in their work. The objectives of this study were to investigate how professionals visiting animal farms in Sweden in their daily work perceive the on-farm conditions for biosecurity, the factors that influence their own biosecurity routines and what they describe as obstacles for biosecurity. Suggestions for improvements were also asked for. Questionnaires were distributed to professionals visiting farms in their daily work; veterinarians, livestock hauliers, artificial insemination technicians, animal welfare inspectors and cattle hoof trimmers. The sample was a convenience sample, based on accessibility to registers or collaboration with organisations distributing the questionnaire. Respondents were asked about the availability of certain biosecurity conditions related to farm visits, e.g. if facilities for hand washing were available, how important different factors were for their own routines and, through open ended questions, to describe obstacles and suggestions for improvement. RESULTS: After data cleaning, there were responses from 368 persons. There was a difference in the proportion of visited farms reported to have certain biosecurity measures in place related to animal species present on the farm. In general, visited pig farms had a higher proportion of biosecurity measures in place, whereas the conditions were poorer on sheep and goat farms and horse farms. There were also differences between the visitor categories; the perceived conditions for biosecurity varied between the groups, e.g. livestock hauliers did not have access to hand washing facilities as often as veterinarians did. In all groups, a majority of the respondents perceived obstacles for on-farm biosecurity, among veterinarians 66% perceived that there were obstacles. Many of the reported obstacles related to the very basics of biosecurity, such as access to soap and water. Responsibility was identified to be a key issue; while some farmers expect visitors to take responsibility for keeping up biosecurity they do not provide the adequate on-farm conditions. CONCLUSIONS: Many of the respondents reported obstacles for keeping good biosecurity related to on-farm conditions. There was a gap when it came to responsibility which needs to be clarified. Visitors need to take responsibility for avoiding spread of disease, while farmers need to assume responsibility for providing adequate conditions for on-farm biosecurity.",2014 May 9,"['Nöremark, Maria', 'Sternberg-Lewerin, Susanna']",Acta Vet Scand,,,False
1cd5431db44d6562cfea3d77b51e079b13bc917f,PMC,On-farm biosecurity as perceived by professionals visiting Swedish farms,http://dx.doi.org/10.1186/1751-0147-56-28,PMC4036743,24886408,CC BY,"BACKGROUND: On-farm biosecurity is an important part of disease prevention and control, this applies to live animal contacts as well as indirect contacts e.g. via professionals visiting farms in their work. The objectives of this study were to investigate how professionals visiting animal farms in Sweden in their daily work perceive the on-farm conditions for biosecurity, the factors that influence their own biosecurity routines and what they describe as obstacles for biosecurity. Suggestions for improvements were also asked for. Questionnaires were distributed to professionals visiting farms in their daily work; veterinarians, livestock hauliers, artificial insemination technicians, animal welfare inspectors and cattle hoof trimmers. The sample was a convenience sample, based on accessibility to registers or collaboration with organisations distributing the questionnaire. Respondents were asked about the availability of certain biosecurity conditions related to farm visits, e.g. if facilities for hand washing were available, how important different factors were for their own routines and, through open ended questions, to describe obstacles and suggestions for improvement. RESULTS: After data cleaning, there were responses from 368 persons. There was a difference in the proportion of visited farms reported to have certain biosecurity measures in place related to animal species present on the farm. In general, visited pig farms had a higher proportion of biosecurity measures in place, whereas the conditions were poorer on sheep and goat farms and horse farms. There were also differences between the visitor categories; the perceived conditions for biosecurity varied between the groups, e.g. livestock hauliers did not have access to hand washing facilities as often as veterinarians did. In all groups, a majority of the respondents perceived obstacles for on-farm biosecurity, among veterinarians 66% perceived that there were obstacles. Many of the reported obstacles related to the very basics of biosecurity, such as access to soap and water. Responsibility was identified to be a key issue; while some farmers expect visitors to take responsibility for keeping up biosecurity they do not provide the adequate on-farm conditions. CONCLUSIONS: Many of the respondents reported obstacles for keeping good biosecurity related to on-farm conditions. There was a gap when it came to responsibility which needs to be clarified. Visitors need to take responsibility for avoiding spread of disease, while farmers need to assume responsibility for providing adequate conditions for on-farm biosecurity.",2014 May 9,"['Nöremark, Maria', 'Sternberg-Lewerin, Susanna']",Acta Vet Scand,,,False
dc1e16996462dd1445f21c419b6e40dd0dd84c02,PMC,Asymmetrically interacting spreading dynamics on complex layered networks,http://dx.doi.org/10.1038/srep05097,PMC4037715,24872257,CC BY,"The spread of disease through a physical-contact network and the spread of information about the disease on a communication network are two intimately related dynamical processes. We investigate the asymmetrical interplay between the two types of spreading dynamics, each occurring on its own layer, by focusing on the two fundamental quantities underlying any spreading process: epidemic threshold and the final infection ratio. We find that an epidemic outbreak on the contact layer can induce an outbreak on the communication layer, and information spreading can effectively raise the epidemic threshold. When structural correlation exists between the two layers, the information threshold remains unchanged but the epidemic threshold can be enhanced, making the contact layer more resilient to epidemic outbreak. We develop a physical theory to understand the intricate interplay between the two types of spreading dynamics.",2014 May 29,"['Wang, Wei', 'Tang, Ming', 'Yang, Hui', 'Younghae Do', 'Lai, Ying-Cheng', 'Lee, GyuWon']",Sci Rep,,,True
354a4b199eb297756554a8967154ea32f07e88d1,PMC,Asymmetrically interacting spreading dynamics on complex layered networks,http://dx.doi.org/10.1038/srep05097,PMC4037715,24872257,CC BY,"The spread of disease through a physical-contact network and the spread of information about the disease on a communication network are two intimately related dynamical processes. We investigate the asymmetrical interplay between the two types of spreading dynamics, each occurring on its own layer, by focusing on the two fundamental quantities underlying any spreading process: epidemic threshold and the final infection ratio. We find that an epidemic outbreak on the contact layer can induce an outbreak on the communication layer, and information spreading can effectively raise the epidemic threshold. When structural correlation exists between the two layers, the information threshold remains unchanged but the epidemic threshold can be enhanced, making the contact layer more resilient to epidemic outbreak. We develop a physical theory to understand the intricate interplay between the two types of spreading dynamics.",2014 May 29,"['Wang, Wei', 'Tang, Ming', 'Yang, Hui', 'Younghae Do', 'Lai, Ying-Cheng', 'Lee, GyuWon']",Sci Rep,,,True
f8b28dc077a4d62178940c43350079dd6b0b91bd,PMC,Mesoniviruses are mosquito-specific viruses with extensive geographic distribution and host range,http://dx.doi.org/10.1186/1743-422X-11-97,PMC4038087,24884700,CC BY,"BACKGROUND: The family Mesoniviridae (order Nidovirales) comprises of a group of positive-sense, single-stranded RNA ([+]ssRNA) viruses isolated from mosquitoes. FINDINGS: Thirteen novel insect-specific virus isolates were obtained from mosquitoes collected in Indonesia, Thailand and the USA. By electron microscopy, the virions appeared as spherical particles with a diameter of ~50 nm. Their 20,129 nt to 20,777 nt genomes consist of positive-sense, single-stranded RNA with a poly-A tail. Four isolates from Houston, Texas, and one isolate from Java, Indonesia, were identified as variants of the species Alphamesonivirus-1 which also includes Nam Dinh virus (NDiV) from Vietnam and Cavally virus (CavV) from Côte d’Ivoire. The eight other isolates were identified as variants of three new mesoniviruses, based on genome organization and pairwise evolutionary distances: Karang Sari virus (KSaV) from Java, Bontag Baru virus (BBaV) from Java and Kalimantan, and Kamphaeng Phet virus (KPhV) from Thailand. In comparison with NDiV, the three new mesoniviruses each contained a long insertion (180 – 588 nt) of unknown function in the 5’ region of ORF1a, which accounted for much of the difference in genome size. The insertions contained various short imperfect repeats and may have arisen by recombination or sequence duplication. CONCLUSIONS: In summary, based on their genome organizations and phylogenetic relationships, thirteen new viruses were identified as members of the family Mesoniviridae, order Nidovirales. Species demarcation criteria employed previously for mesoniviruses would place five of these isolates in the same species as NDiV and CavV (Alphamesonivirus-1) and the other eight isolates would represent three new mesonivirus species (Alphamesonivirus-5, Alphamesonivirus-6 and Alphamesonivirus-7). The observed spatiotemporal distribution over widespread geographic regions and broad species host range in mosquitoes suggests that mesoniviruses may be common in mosquito populations worldwide.",2014 May 20,"['Vasilakis, Nikos', 'Guzman, Hilda', 'Firth, Cadhla', 'Forrester, Naomi L', 'Widen, Steven G', 'Wood, Thomas G', 'Rossi, Shannan L', 'Ghedin, Elodie', 'Popov, Vsevolov', 'Blasdell, Kim R', 'Walker, Peter J', 'Tesh, Robert B']",Virol J,,,True
586244c9f0237c8e2ad291d176ec1705a04ddea6,PMC,Mesoniviruses are mosquito-specific viruses with extensive geographic distribution and host range,http://dx.doi.org/10.1186/1743-422X-11-97,PMC4038087,24884700,CC BY,"BACKGROUND: The family Mesoniviridae (order Nidovirales) comprises of a group of positive-sense, single-stranded RNA ([+]ssRNA) viruses isolated from mosquitoes. FINDINGS: Thirteen novel insect-specific virus isolates were obtained from mosquitoes collected in Indonesia, Thailand and the USA. By electron microscopy, the virions appeared as spherical particles with a diameter of ~50 nm. Their 20,129 nt to 20,777 nt genomes consist of positive-sense, single-stranded RNA with a poly-A tail. Four isolates from Houston, Texas, and one isolate from Java, Indonesia, were identified as variants of the species Alphamesonivirus-1 which also includes Nam Dinh virus (NDiV) from Vietnam and Cavally virus (CavV) from Côte d’Ivoire. The eight other isolates were identified as variants of three new mesoniviruses, based on genome organization and pairwise evolutionary distances: Karang Sari virus (KSaV) from Java, Bontag Baru virus (BBaV) from Java and Kalimantan, and Kamphaeng Phet virus (KPhV) from Thailand. In comparison with NDiV, the three new mesoniviruses each contained a long insertion (180 – 588 nt) of unknown function in the 5’ region of ORF1a, which accounted for much of the difference in genome size. The insertions contained various short imperfect repeats and may have arisen by recombination or sequence duplication. CONCLUSIONS: In summary, based on their genome organizations and phylogenetic relationships, thirteen new viruses were identified as members of the family Mesoniviridae, order Nidovirales. Species demarcation criteria employed previously for mesoniviruses would place five of these isolates in the same species as NDiV and CavV (Alphamesonivirus-1) and the other eight isolates would represent three new mesonivirus species (Alphamesonivirus-5, Alphamesonivirus-6 and Alphamesonivirus-7). The observed spatiotemporal distribution over widespread geographic regions and broad species host range in mosquitoes suggests that mesoniviruses may be common in mosquito populations worldwide.",2014 May 20,"['Vasilakis, Nikos', 'Guzman, Hilda', 'Firth, Cadhla', 'Forrester, Naomi L', 'Widen, Steven G', 'Wood, Thomas G', 'Rossi, Shannan L', 'Ghedin, Elodie', 'Popov, Vsevolov', 'Blasdell, Kim R', 'Walker, Peter J', 'Tesh, Robert B']",Virol J,,,False
53c724259063603c2e3676cbce495688151db443,PMC,Mesoniviruses are mosquito-specific viruses with extensive geographic distribution and host range,http://dx.doi.org/10.1186/1743-422X-11-97,PMC4038087,24884700,CC BY,"BACKGROUND: The family Mesoniviridae (order Nidovirales) comprises of a group of positive-sense, single-stranded RNA ([+]ssRNA) viruses isolated from mosquitoes. FINDINGS: Thirteen novel insect-specific virus isolates were obtained from mosquitoes collected in Indonesia, Thailand and the USA. By electron microscopy, the virions appeared as spherical particles with a diameter of ~50 nm. Their 20,129 nt to 20,777 nt genomes consist of positive-sense, single-stranded RNA with a poly-A tail. Four isolates from Houston, Texas, and one isolate from Java, Indonesia, were identified as variants of the species Alphamesonivirus-1 which also includes Nam Dinh virus (NDiV) from Vietnam and Cavally virus (CavV) from Côte d’Ivoire. The eight other isolates were identified as variants of three new mesoniviruses, based on genome organization and pairwise evolutionary distances: Karang Sari virus (KSaV) from Java, Bontag Baru virus (BBaV) from Java and Kalimantan, and Kamphaeng Phet virus (KPhV) from Thailand. In comparison with NDiV, the three new mesoniviruses each contained a long insertion (180 – 588 nt) of unknown function in the 5’ region of ORF1a, which accounted for much of the difference in genome size. The insertions contained various short imperfect repeats and may have arisen by recombination or sequence duplication. CONCLUSIONS: In summary, based on their genome organizations and phylogenetic relationships, thirteen new viruses were identified as members of the family Mesoniviridae, order Nidovirales. Species demarcation criteria employed previously for mesoniviruses would place five of these isolates in the same species as NDiV and CavV (Alphamesonivirus-1) and the other eight isolates would represent three new mesonivirus species (Alphamesonivirus-5, Alphamesonivirus-6 and Alphamesonivirus-7). The observed spatiotemporal distribution over widespread geographic regions and broad species host range in mosquitoes suggests that mesoniviruses may be common in mosquito populations worldwide.",2014 May 20,"['Vasilakis, Nikos', 'Guzman, Hilda', 'Firth, Cadhla', 'Forrester, Naomi L', 'Widen, Steven G', 'Wood, Thomas G', 'Rossi, Shannan L', 'Ghedin, Elodie', 'Popov, Vsevolov', 'Blasdell, Kim R', 'Walker, Peter J', 'Tesh, Robert B']",Virol J,,,False
8781ae40cadd5a251e316e944c0b331e16094f5d,PMC,Mesoniviruses are mosquito-specific viruses with extensive geographic distribution and host range,http://dx.doi.org/10.1186/1743-422X-11-97,PMC4038087,24884700,CC BY,"BACKGROUND: The family Mesoniviridae (order Nidovirales) comprises of a group of positive-sense, single-stranded RNA ([+]ssRNA) viruses isolated from mosquitoes. FINDINGS: Thirteen novel insect-specific virus isolates were obtained from mosquitoes collected in Indonesia, Thailand and the USA. By electron microscopy, the virions appeared as spherical particles with a diameter of ~50 nm. Their 20,129 nt to 20,777 nt genomes consist of positive-sense, single-stranded RNA with a poly-A tail. Four isolates from Houston, Texas, and one isolate from Java, Indonesia, were identified as variants of the species Alphamesonivirus-1 which also includes Nam Dinh virus (NDiV) from Vietnam and Cavally virus (CavV) from Côte d’Ivoire. The eight other isolates were identified as variants of three new mesoniviruses, based on genome organization and pairwise evolutionary distances: Karang Sari virus (KSaV) from Java, Bontag Baru virus (BBaV) from Java and Kalimantan, and Kamphaeng Phet virus (KPhV) from Thailand. In comparison with NDiV, the three new mesoniviruses each contained a long insertion (180 – 588 nt) of unknown function in the 5’ region of ORF1a, which accounted for much of the difference in genome size. The insertions contained various short imperfect repeats and may have arisen by recombination or sequence duplication. CONCLUSIONS: In summary, based on their genome organizations and phylogenetic relationships, thirteen new viruses were identified as members of the family Mesoniviridae, order Nidovirales. Species demarcation criteria employed previously for mesoniviruses would place five of these isolates in the same species as NDiV and CavV (Alphamesonivirus-1) and the other eight isolates would represent three new mesonivirus species (Alphamesonivirus-5, Alphamesonivirus-6 and Alphamesonivirus-7). The observed spatiotemporal distribution over widespread geographic regions and broad species host range in mosquitoes suggests that mesoniviruses may be common in mosquito populations worldwide.",2014 May 20,"['Vasilakis, Nikos', 'Guzman, Hilda', 'Firth, Cadhla', 'Forrester, Naomi L', 'Widen, Steven G', 'Wood, Thomas G', 'Rossi, Shannan L', 'Ghedin, Elodie', 'Popov, Vsevolov', 'Blasdell, Kim R', 'Walker, Peter J', 'Tesh, Robert B']",Virol J,,,False
312f7d52c437036fdc131e828cd4c86ff3886a0e,PMC,Mesoniviruses are mosquito-specific viruses with extensive geographic distribution and host range,http://dx.doi.org/10.1186/1743-422X-11-97,PMC4038087,24884700,CC BY,"BACKGROUND: The family Mesoniviridae (order Nidovirales) comprises of a group of positive-sense, single-stranded RNA ([+]ssRNA) viruses isolated from mosquitoes. FINDINGS: Thirteen novel insect-specific virus isolates were obtained from mosquitoes collected in Indonesia, Thailand and the USA. By electron microscopy, the virions appeared as spherical particles with a diameter of ~50 nm. Their 20,129 nt to 20,777 nt genomes consist of positive-sense, single-stranded RNA with a poly-A tail. Four isolates from Houston, Texas, and one isolate from Java, Indonesia, were identified as variants of the species Alphamesonivirus-1 which also includes Nam Dinh virus (NDiV) from Vietnam and Cavally virus (CavV) from Côte d’Ivoire. The eight other isolates were identified as variants of three new mesoniviruses, based on genome organization and pairwise evolutionary distances: Karang Sari virus (KSaV) from Java, Bontag Baru virus (BBaV) from Java and Kalimantan, and Kamphaeng Phet virus (KPhV) from Thailand. In comparison with NDiV, the three new mesoniviruses each contained a long insertion (180 – 588 nt) of unknown function in the 5’ region of ORF1a, which accounted for much of the difference in genome size. The insertions contained various short imperfect repeats and may have arisen by recombination or sequence duplication. CONCLUSIONS: In summary, based on their genome organizations and phylogenetic relationships, thirteen new viruses were identified as members of the family Mesoniviridae, order Nidovirales. Species demarcation criteria employed previously for mesoniviruses would place five of these isolates in the same species as NDiV and CavV (Alphamesonivirus-1) and the other eight isolates would represent three new mesonivirus species (Alphamesonivirus-5, Alphamesonivirus-6 and Alphamesonivirus-7). The observed spatiotemporal distribution over widespread geographic regions and broad species host range in mosquitoes suggests that mesoniviruses may be common in mosquito populations worldwide.",2014 May 20,"['Vasilakis, Nikos', 'Guzman, Hilda', 'Firth, Cadhla', 'Forrester, Naomi L', 'Widen, Steven G', 'Wood, Thomas G', 'Rossi, Shannan L', 'Ghedin, Elodie', 'Popov, Vsevolov', 'Blasdell, Kim R', 'Walker, Peter J', 'Tesh, Robert B']",Virol J,,,False
28a01c582588f326714549b5f7ba16515175666f,PMC,Mesoniviruses are mosquito-specific viruses with extensive geographic distribution and host range,http://dx.doi.org/10.1186/1743-422X-11-97,PMC4038087,24884700,CC BY,"BACKGROUND: The family Mesoniviridae (order Nidovirales) comprises of a group of positive-sense, single-stranded RNA ([+]ssRNA) viruses isolated from mosquitoes. FINDINGS: Thirteen novel insect-specific virus isolates were obtained from mosquitoes collected in Indonesia, Thailand and the USA. By electron microscopy, the virions appeared as spherical particles with a diameter of ~50 nm. Their 20,129 nt to 20,777 nt genomes consist of positive-sense, single-stranded RNA with a poly-A tail. Four isolates from Houston, Texas, and one isolate from Java, Indonesia, were identified as variants of the species Alphamesonivirus-1 which also includes Nam Dinh virus (NDiV) from Vietnam and Cavally virus (CavV) from Côte d’Ivoire. The eight other isolates were identified as variants of three new mesoniviruses, based on genome organization and pairwise evolutionary distances: Karang Sari virus (KSaV) from Java, Bontag Baru virus (BBaV) from Java and Kalimantan, and Kamphaeng Phet virus (KPhV) from Thailand. In comparison with NDiV, the three new mesoniviruses each contained a long insertion (180 – 588 nt) of unknown function in the 5’ region of ORF1a, which accounted for much of the difference in genome size. The insertions contained various short imperfect repeats and may have arisen by recombination or sequence duplication. CONCLUSIONS: In summary, based on their genome organizations and phylogenetic relationships, thirteen new viruses were identified as members of the family Mesoniviridae, order Nidovirales. Species demarcation criteria employed previously for mesoniviruses would place five of these isolates in the same species as NDiV and CavV (Alphamesonivirus-1) and the other eight isolates would represent three new mesonivirus species (Alphamesonivirus-5, Alphamesonivirus-6 and Alphamesonivirus-7). The observed spatiotemporal distribution over widespread geographic regions and broad species host range in mosquitoes suggests that mesoniviruses may be common in mosquito populations worldwide.",2014 May 20,"['Vasilakis, Nikos', 'Guzman, Hilda', 'Firth, Cadhla', 'Forrester, Naomi L', 'Widen, Steven G', 'Wood, Thomas G', 'Rossi, Shannan L', 'Ghedin, Elodie', 'Popov, Vsevolov', 'Blasdell, Kim R', 'Walker, Peter J', 'Tesh, Robert B']",Virol J,,,False
2ebf1526911eca26db1a7933e592260302caa3b7,PMC,A Novel Universal Neutralizing Monoclonal Antibody against Enterovirus 71 That Targets the Highly Conserved “Knob” Region of VP3 Protein,http://dx.doi.org/10.1371/journal.pntd.0002895,PMC4038473,24875055,CC BY,"Hand, foot and mouth disease caused by enterovirus 71(EV71) leads to the majority of neurological complications and death in young children. While putative inactivated vaccines are only now undergoing clinical trials, no specific treatment options exist yet. Ideally, EV71 specific intravenous immunoglobulins could be developed for targeted treatment of severe cases. To date, only a single universally neutralizing monoclonal antibody against a conserved linear epitope of VP1 has been identified. Other enteroviruses have been shown to possess major conformational neutralizing epitopes on both the VP2 and VP3 capsid proteins. Hence, we attempted to isolate such neutralizing antibodies against conformational epitopes for their potential in the treatment of infection as well as differential diagnosis and vaccine optimization. Here we describe a universal neutralizing monoclonal antibody that recognizes a conserved conformational epitope of EV71 which was mapped using escape mutants. Eight escape mutants from different subgenogroups (A, B2, B4, C2, C4) were rescued; they harbored three essential mutations either at amino acid positions 59, 62 or 67 of the VP3 protein which are all situated in the “knob” region. The escape mutant phenotype could be mimicked by incorporating these mutations into reverse genetically engineered viruses showing that P59L, A62D, A62P and E67D abolish both monoclonal antibody binding and neutralization activity. This is the first conformational neutralization epitope mapped on VP3 for EV71.",2014 May 29,"['Kiener, Tanja K.', 'Jia, Qiang', 'Meng, Tao', 'Chow, Vincent Tak Kwong', 'Kwang, Jimmy']",PLoS Negl Trop Dis,,,True
d0bace106b5562f5e1cf5b124331f9c526d46d21,PMC,Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts,http://dx.doi.org/10.1371/journal.pgen.1004403,PMC4038475,24875882,CC BY,"Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.",2014 May 29,"['Daugherty, Matthew D.', 'Young, Janet M.', 'Kerns, Julie A.', 'Malik, Harmit S.']",PLoS Genet,,,True
6fd2d02aa0a14ee3abc038a93632b9a53231c004,PMC,Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts,http://dx.doi.org/10.1371/journal.pgen.1004403,PMC4038475,24875882,CC BY,"Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.",2014 May 29,"['Daugherty, Matthew D.', 'Young, Janet M.', 'Kerns, Julie A.', 'Malik, Harmit S.']",PLoS Genet,,,False
ffb2127ddb0f8548f3f9a5e2da25a8d716c1dc56,PMC,Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts,http://dx.doi.org/10.1371/journal.pgen.1004403,PMC4038475,24875882,CC BY,"Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.",2014 May 29,"['Daugherty, Matthew D.', 'Young, Janet M.', 'Kerns, Julie A.', 'Malik, Harmit S.']",PLoS Genet,,,False
bf98247f3fce1a28bd9b3eefb26265c83dfb4883,PMC,Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts,http://dx.doi.org/10.1371/journal.pgen.1004403,PMC4038475,24875882,CC BY,"Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.",2014 May 29,"['Daugherty, Matthew D.', 'Young, Janet M.', 'Kerns, Julie A.', 'Malik, Harmit S.']",PLoS Genet,,,False
cccd00693812328980f4652e418319de1d27c455,PMC,Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts,http://dx.doi.org/10.1371/journal.pgen.1004403,PMC4038475,24875882,CC BY,"Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.",2014 May 29,"['Daugherty, Matthew D.', 'Young, Janet M.', 'Kerns, Julie A.', 'Malik, Harmit S.']",PLoS Genet,,,False
8476daf05ad6126ff4f5a6fedee2e3c7b8faecbb,PMC,Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts,http://dx.doi.org/10.1371/journal.pgen.1004403,PMC4038475,24875882,CC BY,"Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.",2014 May 29,"['Daugherty, Matthew D.', 'Young, Janet M.', 'Kerns, Julie A.', 'Malik, Harmit S.']",PLoS Genet,,,False
315d4cc4aa30d30ddab0007ac05b4c817a4617f4,PMC,Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts,http://dx.doi.org/10.1371/journal.pgen.1004403,PMC4038475,24875882,CC BY,"Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.",2014 May 29,"['Daugherty, Matthew D.', 'Young, Janet M.', 'Kerns, Julie A.', 'Malik, Harmit S.']",PLoS Genet,,,False
52dfb9ce5951426c5fb9ad7bf82186038938ab66,PMC,Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts,http://dx.doi.org/10.1371/journal.pgen.1004403,PMC4038475,24875882,CC BY,"Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.",2014 May 29,"['Daugherty, Matthew D.', 'Young, Janet M.', 'Kerns, Julie A.', 'Malik, Harmit S.']",PLoS Genet,,,False
17dbd5741595c1e5b7508063b31147be9263e7f0,PMC,Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus,http://dx.doi.org/10.1371/journal.ppat.1004166,PMC4038610,24874215,CC BY,"Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS–CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections.",2014 May 29,"['Lundin, Anna', 'Dijkman, Ronald', 'Bergström, Tomas', 'Kann, Nina', 'Adamiak, Beata', 'Hannoun, Charles', 'Kindler, Eveline', 'Jónsdóttir, Hulda R.', 'Muth, Doreen', 'Kint, Joeri', 'Forlenza, Maria', 'Müller, Marcel A.', 'Drosten, Christian', 'Thiel, Volker', 'Trybala, Edward']",PLoS Pathog,,,True
0899d745009fa75954f75b381c040aebd927832a,PMC,The evolution of disease: anthropological perspectives on epidemiologic transitions,http://dx.doi.org/10.3402/gha.v7.23303,PMC4038768,24848652,CC BY,"BACKGROUND: The model of epidemiologic transitions has served as a guiding framework for understanding relationships between patterns of human health and disease and economic development for the past several decades. However, epidemiologic transition theory is infrequently employed in epidemiology. OBJECTIVE: Moving beyond Omran's original formulation, we discuss critiques and modifications of the theory of epidemiologic transitions and highlight some of the ways in which incorporating epidemiologic transition theory can benefit theory and practice in epidemiology. DESIGN: We focus on two broad contemporary trends in human health that epidemiologic transition theory is useful for conceptualizing: the increased incidence of chronic inflammatory diseases (CIDs), such as allergic and autoimmune diseases, and the emergence and reemergence of infectious disease. RESULTS: Situating these trends within epidemiologic transition theory, we explain the rise in CIDs with the hygiene hypothesis and the rise in emerging and reemerging infections with the concept of a third epidemiologic transition. CONCLUSIONS: Contextualizing these trends within epidemiologic transition theory reveals implications for clinical practice, global health policies, and future research within epidemiology.",2014 May 15,"['Zuckerman, Molly Kathleen', 'Harper, Kristin Nicole', 'Barrett, Ronald', 'Armelagos, George John']",Glob Health Action,,,True
20905ce137d4d5735c25f22352a653f3ebcbc4fc,PMC,Full-Genome Sequence of Human Betacoronavirus 2c Jordan-N3/2012 after Serial Passage in Mammalian Cells,http://dx.doi.org/10.1128/genomeA.00324-14,PMC4038873,24874668,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is the etiologic agent of a highly lethal pneumonia. Here, we report the full-genome sequence of the Jordan-N3/2012 strain after serial passage in two distinct mammalian cell lines. The genome exhibits noteworthy stability, which may inform the development of vaccines and therapeutics used to treat infection with this virus.",2014 May 29,"['Frey, Kenneth G.', 'Redden, Cassie L.', 'Bishop-Lilly, Kimberly A.', 'Johnson, Reed', 'Hensley, Lisa E.', 'Raviprakash, Kanakatte', 'Luke, Thomas', 'Kochel, Tad', 'Mokashi, Vishwesh P.', 'Defang, Gabriel N.']",Genome Announc,,,True
f34cdf2bec51c797567dedf6f00954351ebe5320,PMC,"Genome Sequence of the Novel Reassortant Mammalian Orthoreovirus Strain MRV00304/13, Isolated from a Calf with Diarrhea from the United States",http://dx.doi.org/10.1128/genomeA.00451-14,PMC4038876,24874671,CC BY,"Mammalian orthoreovirus (MRV) strain MRV00304/13 was isolated from diarrheic calves. The serotype-specific antigen σ1 was found to be 95% identical to that of bovine MRV1. All predicted viral proteins had >92% identity to those of MRV except µ2 and σ1s (80 and 72% identities, respectively), suggesting that MRV00304/13 is a novel reassortant MRV1.",2014 May 29,"['Anbalagan, Srivishnupriya', 'Spaans, Tina', 'Hause, Ben M.']",Genome Announc,,,True
59d6529a7cd680c358b3caf56b8517ad61b82aca,PMC,"Complete Genome Sequence of K14JB01, a Novel Variant Strain of Porcine Epidemic Diarrhea Virus in South Korea",http://dx.doi.org/10.1128/genomeA.00505-14,PMC4038887,24874682,CC BY,A novel variant strain of porcine epidemic diarrhea virus (PEDV) emerged on pig farms in South Korea during late 2013. Genomic DNA isolated from a K14JB01 strain identified in a diarrheal pig showed high sequence similarity to PEDV strains prevailing in the United States in 2013. This is the first study to identify the complete genome sequence of a novel variant PEDV in South Korea.,2014 May 29,"['Cho, Yoon-Young', 'Lim, Seong-In', 'Kim, Yong Kwan', 'Song, Jae-Young', 'Lee, Joong-Bok', 'An, Dong-Jun']",Genome Announc,,,True
6bba4b00882498efa69f66a1a92b1c240acfd2a9,PMC,Actinobacillus pleuropneumoniae Possesses an Antiviral Activity against Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1371/journal.pone.0098434,PMC4039538,24878741,CC BY,"Pigs are often colonized by more than one bacterial and/or viral species during respiratory tract infections. This phenomenon is known as the porcine respiratory disease complex (PRDC). Actinobacillus pleuropneumoniae (App) and porcine reproductive and respiratory syndrome virus (PRRSV) are pathogens that are frequently involved in PRDC. The main objective of this project was to study the in vitro interactions between these two pathogens and the host cells in the context of mixed infections. To fulfill this objective, PRRSV permissive cell lines such as MARC-145, SJPL, and porcine alveolar macrophages (PAM) were used. A pre-infection with PRRSV was performed at 0.5 multiplicity of infection (MOI) followed by an infection with App at 10 MOI. Bacterial adherence and cell death were compared. Results showed that PRRSV pre-infection did not affect bacterial adherence to the cells. PRRSV and App co-infection produced an additive cytotoxicity effect. Interestingly, a pre-infection of SJPL and PAM cells with App blocked completely PRRSV infection. Incubation of SJPL and PAM cells with an App cell-free culture supernatant is also sufficient to significantly block PRRSV infection. This antiviral activity is not due to LPS but rather by small molecular weight, heat-resistant App metabolites (<1 kDa). The antiviral activity was also observed in SJPL cells infected with swine influenza virus but to a much lower extent compared to PRRSV. More importantly, the PRRSV antiviral activity of App was also seen with PAM, the cells targeted by the virus in vivo during infection in pigs. The antiviral activity might be due, at least in part, to the production of interferon γ. The use of in vitro experimental models to study viral and bacterial co-infections will lead to a better understanding of the interactions between pathogens and their host cells, and could allow the development of novel prophylactic and therapeutic tools.",2014 May 30,"['Lévesque, Cynthia', 'Provost, Chantale', 'Labrie, Josée', 'Hernandez Reyes, Yenney', 'Burciaga Nava, Jorge A.', 'Gagnon, Carl A.', 'Jacques, Mario']",PLoS One,,,True
b31d9e4a450071584fa87e054414be87264def22,PMC,Vitamin D(3) and gargling for the prevention of upper respiratory tract infections: a randomized controlled trial,http://dx.doi.org/10.1186/1471-2334-14-273,PMC4041358,24885201,CC BY,"BACKGROUND: We undertook a 2X2 factorial, randomized controlled trial (RCT) to assess whether vitamin D(3) supplementation (10,000 international units per week) versus placebo and gargling versus no gargling could prevent viral, clinical upper respiratory tract infection (URTI) in university students. METHODS: We randomized 600 students into 4 treatment arms: 1) vitamin D(3) and gargling, 2) placebo and gargling, 3) vitamin D(3) and no gargling, and 4) placebo and no gargling. Students completed weekly electronic surveys and submitted self-collected mid-turbinate nasal flocked swabs during September and October in 2010 or 2011. Symptomatic students also completed an electronic symptom diary. The primary and secondary outcomes were the occurrence of symptomatic clinical URTI and laboratory confirmed URTI respectively. RESULTS: Of 600 participants, 471 (78.5%) completed all surveys while 43 (7.2%) completed none; 150 (25.0%) reported clinical URTI. Seventy participants (23.3%) randomized to vitamin D(3) reported clinical URTI compared to 80 (26.7%) randomized to placebo (RR:0.79, CI(95):0.61-1.03, p = 0.09). Eighty-five participants (28.3%) randomized to gargling reported clinical URTI compared to 65 participants (21.7%) randomized to the no gargling arm (RR:1.3, CI(95):0.92-1.57, p = 0.19). Laboratory testing identified 70 infections (46.7 per 100 URTIs). Vitamin D(3) treatment was associated with a significantly lower risk for laboratory confirmed URTI (RR: 0.54, CI(95):0.34-0.84, p = 0.007) and with a significantly lower mean viral load measured as log(10) viral copies/mL (mean difference: -0.89, CI(95:) -1.7, -0.06, p = 0.04). Fewer students assigned to gargling experienced laboratory confirmed URTI, however this was not statistically significant (RR:0.82, CI(95):0.53-1.26, p = 0.36). CONCLUSIONS: These results suggest that vitamin D(3) is a promising intervention for the prevention of URTI. Vitamin D(3) significantly reduced the risk of laboratory confirmed URTI and may reduce the risk of clinical infections. TRIAL REGISTRATION: Clinical Trials Registration: NCT01158560.",2014 May 19,"['Goodall, Emma C', 'Granados, Andrea C', 'Luinstra, Kathy', 'Pullenayegum, Eleanor', 'Coleman, Brenda L', 'Loeb, Mark', 'Smieja, Marek']",BMC Infect Dis,,,True
bdd4a8a3507c4df13f06d8693ce8d6b4e9d6c3af,PMC,Identification and genotyping of feline infectious peritonitis-associated single nucleotide polymorphisms in the feline interferon-γ gene,http://dx.doi.org/10.1186/1297-9716-45-57,PMC4041894,24886103,CC BY,"Feline infectious peritonitis (FIP) is an immune-mediated, highly lethal disease caused by feline coronavirus (FCoV) infection. Currently, no protective vaccine or effective treatment for the disease is available. Studies have found that some cats survive the challenge of virulent FCoV isolates. Since cellular immunity is thought to be critical in preventing FIP and because diseased cats often show a significant decrease in interferon-γ (IFN-γ) production, we investigated whether single nucleotide polymorphisms (SNP) in the feline IFN-γ gene (fIFNG) are associated with the outcome of infection. A total of 82 asymptomatic and 63 FIP cats were analyzed, and 16 SNP were identified in intron 1 of fIFNG. Among these SNP, the fFING + 428 T allele was shown to be a FIP-resistant allele (p = 0.03), and the heterozygous genotypes 01C/T and +408C/T were found to be FIP-susceptible factors (p = 0.004). Furthermore, an fIFNG + 428 resistant allele also showed a clear correlation with the plasma level of IFN-γ in FIP cats. For the identification of these three FIP-related SNP, genotyping methods were established using amplification refractory mutation system PCR (ARMS-PCR) and restriction fragment length polymorphisms (RFLP), and the different genotypes could easily be identified without sequencing. The identification of additional FIP-related SNP will allow the selection of resistant cats and decrease the morbidity of the cat population to FIP.",2014 May 21,"['Hsieh, Li-En', 'Chueh, Ling-Ling']",Vet Res,,,True
ab2859ea36cc85687a9caad282ffaca666bd0b64,PMC,A highly conserved WDYPKCDRA epitope in the RNA directed RNA polymerase of human coronaviruses can be used as epitope-based universal vaccine design,http://dx.doi.org/10.1186/1471-2105-15-161,PMC4041900,24884408,CC BY,"BACKGROUND: Coronaviruses are the diverse group of RNA virus. From 1960, six strains of human coronaviruses have emerged that includes SARS-CoV and the recent infection by deadly MERS-CoV which is now going to cause another outbreak. Prevention of these viruses is urgent and a universal vaccine for all strain could be a promising solution in this circumstance. In this study we aimed to design an epitope based vaccine against all strain of human coronavirus. RESULTS: Multiple sequence alignment (MSA) approach was employed among spike (S), membrane (M), enveloped (E) and nucleocapsid (N) protein and replicase polyprotein 1ab to identify which one is highly conserve in all coronaviruses strains. Next, we use various in silico tools to predict consensus immunogenic and conserved peptide. We found that conserved region is present only in the RNA directed RNA polymerase protein. In this protein we identified one epitope WDYPKCDRA is highly immunogenic and 100% conserved among all available human coronavirus strains. CONCLUSIONS: Here we suggest in vivo study of our identified novel peptide antigen in RNA directed RNA polymerase protein for universal vaccine – which may be the way to prevent all human coronavirus disease.",2014 May 29,"['Sharmin, Refat', 'Islam, Abul Bashar Mir Md Khademul']",BMC Bioinformatics,,,True
3d2fae37d61a2e45cf0dff9bc0abee361bbf9a8d,PMC,Polypeptide N-acetylgalactosaminyltransferase 2 regulates cellular metastasis-associated behavior in gastric cancer,http://dx.doi.org/10.3892/ijmm.2012.1130,PMC4042861,22992780,CC BY,"Aberrant glycosylation of cell surface glycoprotein due to specific alterations of glycosyltransferase activity is usually associated with invasion and metastasis of cancer, particularly of gastric carcinomas. Polypeptide N-acetylgalactosaminyltransferase 2 (ppGalNAc-T2), which catalyzes initiation of mucin-type O-glycosylation, is also involved in tumor migration and invasion. However, a comprehensive understanding of how ppGalNAc-T2 correlates with the metastasic potential of human gastric cancer is not currently available. In the present study, ppGalNAc-T2 was detected in a variety of human poorly differentiated tumor cells, and expression appeared to be higher in SGC7901 gastric cancer cells. In addition, we investigated the potential effects of ppGalNAc-T2 on growth and metastasis-associated behavior in SGC7901 cells after stable transfection with ppGalNAc-T2 sense and antisense vectors. We found that cell proliferation, adhesion and invasion were decreased in ppGalNAc-T2 overexpressed cells but increased in ppGalNAc-T2 downregulated cells. Therefore, we attempted to clarify the mechanisms underlying the anti-metastatic activities of ppGalNAc-T2. Further investigation indicated that overexpression of ppGalNAc-T2 is involved in the inhibition of matrix metalloproteinase (MMP)-2 expression at both the protein and mRNA levels, which may be associated with ppGalNAc-T2 suppressing the expression of transforming growth factor (TGF)-β1. However, it did not exhibit any apparent correlation with MMP-14 expression levels. Our data show the effect of ppGalNAc-T2 on proliferation, adhesion or invasion of SGC7901 gastric cancer cells, suggesting that ppGalNAc-T2 may exert anti-proliferative and anti-metastatic activity through the decrease of MMP-2 and TGF-β1. These results indicate that ppGalNAc-T2 may be used as a novel therapeutic target for human gastric cancer treatment.",2012 Dec 18,"['HUA, DONG', 'SHEN, LI', 'XU, LAN', 'JIANG, ZHI', 'ZHOU, YINGHUI', 'YUE, AIHUAN', 'ZOU, SHITAO', 'CHENG, ZHIHONG', 'WU, SHILIANG']",Int J Mol Med,,,True
98936f4aa8ad9759352811bbb4aa531c2f061cd7,PMC,Inhibitory effect of sodium houttuyfonate on synovial proliferation in vitro in cells from a patient with rheumatoid arthritis,http://dx.doi.org/10.3892/etm.2014.1636,PMC4043587,24926358,CC BY,"The aim of the present study was to investigate the inhibitory effect of sodium houttuyfonate (SH) on synovial cell proliferation in vitro. Primary cells were obtained from the synovial tissue of a patient with rheumatoid arthritis (RA). The cells were divided into five treatment groups as follows: the control group (group 1), 25 μg/ml SH-treated group (group 2), 50 μg/ml SH-treated group (group 3), 100 μg/ml SH-treated group (group 4) and the 200 μg/ml SH-treated group (group 5). Following seven days of treatment, the proliferation rate of the synovial cells was then detected using an MTT assay. The expression level of proliferative synovial cells markedly decreased in the SH-treated groups in a dose-dependent manner compared with the control group. In conclusion, the present study demonstrated that SH was able to inhibit the proliferation of synovial cells obtained from a patient with RA. These results provide a potential theoretical basis for the development of a safe and effective treatment against RA in the future.",2014 Jun 27,"['LI, JUN', 'ZHOU, TING', 'ZHAO, FUTAO']",Exp Ther Med,,,True
5eb1e53fb44c8a997713bd4fc55d65b904df3ce8,PMC,Silver Sucrose Octasulfate (IASOS™) as a Valid Active Ingredient into a Novel Vaginal Gel against Human Vaginal Pathogens: In Vitro Antimicrobial Activity Assessment,http://dx.doi.org/10.1371/journal.pone.0097791,PMC4045761,24897299,CC BY,"This in vitro study assessed the antimicrobial properties of a novel octasilver salt of Sucrose Octasulfate (IASOS) as well as of an innovative vaginal gel containing IASOS (SilSOS Femme), against bacterial and yeast pathogens isolated from human clinical cases of symptomatic vaginal infections. In BHI and LAPT culture media, different ionic silver concentrations and different pHs were tested. IASOS exerted a strong antimicrobial activity towards all the pathogens tested in both culture media. The results demonstrated that salts and organic compounds present in the culture media influenced IASOS efficacy only to a moderate extent. Whereas comparable MBCs (Minimal Bactericidal Concentrations) were observed for G. vaginalis (10 mg/L Ag(+)), E. coli and E. aerogenes (25 mg/L Ag(+)) in both media, higher MBCs were found for S. aureus and S. agalactiae in LAPT cultures (50 mg/L Ag(+) versus 25 mg/L Ag(+)). No minimal concentration totally inhibiting the growth of C. albicans was found. Nevertheless, in both media at the highest ionic silver concentrations (50–200 mg/L Ag(+)), a significant 34–52% drop in Candida growth was observed. pH differently affected the antimicrobial properties of IASOS against bacteria or yeasts; however, a stronger antimicrobial activity at pH higher than the physiological pH was generally observed. It can be therefore concluded that IASOS exerts a bactericidal action against all the tested bacteria and a clear fungistatic action against C. albicans. The antimicrobial activity of the whole vaginal gel SilSOS Femme further confirmed the antimicrobial activity of IASOS. Overall, our findings support IASOS as a valid active ingredient into a vaginal gel.",2014 Jun 4,"['Marianelli, Cinzia', 'Petrucci, Paola', 'Comelli, Maria Cristina', 'Calderini, Gabriella']",PLoS One,,,True
4c4214329dbbf291d7c73b5afb2a145559f780e2,PMC,Decreased expression of eukaryotic initiation factor 3f is an adverse prognostic factor for stage I–III gastric cancer,http://dx.doi.org/10.1186/1477-7819-12-72,PMC4046624,24678890,CC BY,"BACKGROUND: It has been demonstrated that eIF3f expression is significantly decreased in many human cancers, a fact which plays an important role in human cancer. However, the expression of eIF3f in gastric cancer (GC) is not well understood to date. Therefore, the aim of this study is to detect the expression of eIF3f in GC. METHODS: The expression of eIF3f was examined by immunohistochemistry in tissues with stage I to III GC and adjacent non-cancerous tissues (ANCT) of 195 gastrectomy specimens; clinicopathological results, including survival, were analyzed. RESULTS: The positive expression rate of eIF3f was significantly higher in ANCT tissues than in GC. eIF3f levels were correlated with more advanced tumor stages and likelihood of recurrence (all P <0.05). The Kaplan-Meier survival curves indicated that decreased expression of eIF3f could serve as a prognosis marker for poor outcome of GC patients (P = 0.04). CONCLUSIONS: eIF3f may play an important role in recurrence, thus representing a promising predictive marker for the prognosis of GC.",2014 Mar 28,"['Li, Guanghua', 'Wang, Na', 'Sun, Chuanjin', 'Li, Bo']",World J Surg Oncol,,,True
38aa050ad79d8a1d7022c33535255ce9d47914e5,PMC,Potent Inhibition of Junín Virus Infection by Interferon in Murine Cells,http://dx.doi.org/10.1371/journal.pntd.0002933,PMC4046933,24901990,CC BY,"The new world arenavirus Junín virus (JUNV) is the causative agent of Argentine hemorrhagic fever, a lethal human infectious disease. Adult laboratory mice are generally resistant to peripheral infection by JUNV. The mechanism underlying the mouse resistance to JUNV infection is largely unknown. We have reported that interferon receptor knockout mice succumb to JUNV infection, indicating the critical role of interferon in restricting JUNV infection in mice. Here we report that the pathogenic and vaccine strains of JUNV were highly sensitive to interferon in murine primary cells. Treatment with low concentrations of interferon abrogated viral NP protein expression in murine cells. The replication of both JUNVs was enhanced in IRF3/IRF7 deficient cells. In addition, the vaccine strain of JUNV displayed impaired growth in primary murine cells. Our data suggested a direct and potent role of host interferon response in restricting JUNV replication in mice. The defect in viral growth for vaccine JUNV might also partially explain its attenuation in mice.",2014 Jun 5,"['Huang, Cheng', 'Walker, Aida G.', 'Grant, Ashley M.', 'Kolokoltsova, Olga A.', 'Yun, Nadezhda E.', 'Seregin, Alexey V.', 'Paessler, Slobodan']",PLoS Negl Trop Dis,,,True
0326bf875d2a22d7c4a4328dcd34c2d801fd110e,PMC,Neglected Zoonotic Diseases—The Long and Winding Road to Advocacy,http://dx.doi.org/10.1371/journal.pntd.0002800,PMC4046968,24901769,CC BY,"BACKGROUND: Years of advocacy for the neglected tropical diseases (NTDs) have focused the world's attention on these diseases of the poor, resulting most recently in the 2012 “London Declaration” and the recent World Health Assembly Resolution WHA66.12 on NTDs in May 2013. Control of the endemic neglected zoonotic diseases (NZDs) would benefit from a similar campaign, which needs the support of a global community. METHODOLOGY/PRINCIPAL FINDINGS: The resolutions from all 66 World Health Assembly (WHA) meetings held between 1948 and 2013 were examined to determine how many contain a specific focus on any of the following eight NZDs as defined by the World Health Organisation (WHO): anthrax, bovine tuberculosis (TB), brucellosis, Taenia solium cysticercosis, cystic echinococcosis (hydatidosis), leishmaniasis, rabies, and zoonotic human African trypanosomiasis (HAT or sleeping sickness). Twenty-one resolutions adopted in the 16 assemblies between 1948 and 2013 targeted one or more of these eight NZDs, representing 4% of the total resolutions on infectious diseases passed to date. The 2013 adoption of Resolution WHA66.12 targeting all 17 NTDs marks a change in approach by the WHA. Whereas previous resolutions have targeted the NTDs as separate entities, the new approach of the combined resolution will help increase the overall momentum to target these ancient diseases as coendemic clusters in endemic countries. However, three major NZDs remain outside this recent resolution: anthrax, brucellosis, and bovine TB. CONCLUSIONS AND SIGNIFICANCE: The recent adoption of a specific resolution at the WHA in 2013 that emphasises a One Health approach for the successful control of 17 NTDs is a major development in advocacy. However, recognition of the importance of three major NZDs to public health in endemic countries—anthrax, brucellosis, and bovine tuberculosis—is still lacking despite being prioritised by the WHA as early as the 1950s. Global advocacy for control of the NZDs as a whole would similarly benefit from adoption of a One Health approach as is promoted for the NTDs under WHA66.12.",2014 Jun 5,"['Mableson, Hayley E.', 'Okello, Anna', 'Picozzi, Kim', 'Welburn, Susan Christina']",PLoS Negl Trop Dis,,,True
1b248ec38c2c12737c005fd38db1bec556675707,PMC,A Loss of Function Analysis of Host Factors Influencing Vaccinia virus Replication by RNA Interference,http://dx.doi.org/10.1371/journal.pone.0098431,PMC4047015,24901222,CC BY,"Vaccinia virus (VACV) is a large, cytoplasmic, double-stranded DNA virus that requires complex interactions with host proteins in order to replicate. To explore these interactions a functional high throughput small interfering RNA (siRNA) screen targeting 6719 druggable cellular genes was undertaken to identify host factors (HF) influencing the replication and spread of an eGFP-tagged VACV. The experimental design incorporated a low multiplicity of infection, thereby enhancing detection of cellular proteins involved in cell-to-cell spread of VACV. The screen revealed 153 pro- and 149 anti-viral HFs that strongly influenced VACV replication. These HFs were investigated further by comparisons with transcriptional profiling data sets and HFs identified in RNAi screens of other viruses. In addition, functional and pathway analysis of the entire screen was carried out to highlight cellular mechanisms involved in VACV replication. This revealed, as anticipated, that many pro-viral HFs are involved in translation of mRNA and, unexpectedly, suggested that a range of proteins involved in cellular transcriptional processes and several DNA repair pathways possess anti-viral activity. Multiple components of the AMPK complex were found to act as pro-viral HFs, while several septins, a group of highly conserved GTP binding proteins with a role in sequestering intracellular bacteria, were identified as strong anti-viral VACV HFs. This screen has identified novel and previously unexplored roles for cellular factors in poxvirus replication. This advancement in our understanding of the VACV life cycle provides a reliable knowledge base for the improvement of poxvirus-based vaccine vectors and development of anti-viral theraputics.",2014 Jun 5,"['Beard, Philippa M.', 'Griffiths, Samantha J.', 'Gonzalez, Orland', 'Haga, Ismar R.', 'Pechenick Jowers, Tali', 'Reynolds, Danielle K.', 'Wildenhain, Jan', 'Tekotte, Hille', 'Auer, Manfred', 'Tyers, Mike', 'Ghazal, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS One,,,True
10dd2aeb61d54b45337a96f3c6243b72d6764732,PMC,Using HIV Networks to Inform Real Time Prevention Interventions,http://dx.doi.org/10.1371/journal.pone.0098443,PMC4047027,24901437,CC0,"OBJECTIVE: To reconstruct the local HIV-1 transmission network from 1996 to 2011 and use network data to evaluate and guide efforts to interrupt transmission. DESIGN: HIV-1 pol sequence data were analyzed to infer the local transmission network. METHODS: We analyzed HIV-1 pol sequence data to infer a partial local transmission network among 478 recently HIV-1 infected persons and 170 of their sexual and social contacts in San Diego, California. A transmission network score (TNS) was developed to estimate the risk of HIV transmission from a newly diagnosed individual to a new partner and target prevention interventions. RESULTS: HIV-1 pol sequences from 339 individuals (52.3%) were highly similar to sequences from at least one other participant (i.e., clustered). A high TNS (top 25%) was significantly correlated with baseline risk behaviors (number of unique sexual partners and insertive unprotected anal intercourse (p = 0.014 and p = 0.0455, respectively) and predicted risk of transmission (p<0.0001). Retrospective analysis of antiretroviral therapy (ART) use, and simulations of ART targeted to individuals with the highest TNS, showed significantly reduced network level HIV transmission (p<0.05). CONCLUSIONS: Sequence data from an HIV-1 screening program focused on recently infected persons and their social and sexual contacts enabled the characterization of a highly connected transmission network. The network-based risk score (TNS) was highly correlated with transmission risk behaviors and outcomes, and can be used identify and target effective prevention interventions, like ART, to those at a greater risk for HIV-1 transmission.",2014 Jun 5,"['Little, Susan J.', 'Kosakovsky Pond, Sergei L.', 'Anderson, Christy M.', 'Young, Jason A.', 'Wertheim, Joel O.', 'Mehta, Sanjay R.', 'May, Susanne', 'Smith, Davey M.']",PLoS One,,,True
a4995af42a012dd1b7f8da3936d79d78d0e24405,PMC,Interactome Profile of the Host Cellular Proteins and the Nonstructural Protein 2 of Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1371/journal.pone.0099176,PMC4047090,24901321,CC BY,"The nonstructural protein 2 (NSP2) is considered to be one of crucial viral proteins in the replication and pathogenesis of porcine reproductive and respiratory syndrome virus (PRRSV). In the present study, the host cellular proteins that interact with the NSP2 of PRRSV were immunoprecipitated with anti-Myc antibody from the MARC-145 cells infected by a recombinant PRRSV with 3xMyc tag insertion in its NSP2-coding region, and then 285 cellular proteins interacting with NSP2 were identified by LC-MS/MS. The Gene Ontology and enriched KEGG Pathway bioinformatics analyses indicated that the identified proteins could be assigned to different subcellular locations and functional classes. Functional analysis of the interactome profile highlighted cellular pathways associated with infectious disease, translation, immune system, nervous system and signal transduction. Two interested cellular proteins–BCL2-associated athanogene 6 (BAG6) and apoptosis-inducing factor 1 (AIF1) which may involve in transporting of NSP2 to Endoplasmic reticulum (ER) or PRRSV-driven apoptosis were validated by Western blot. The interactome data between PRRSV NSP2 and cellular proteins contribute to the understanding of the roles of NSP2 in the replication and pathogenesis of PRRSV, and also provide novel cellular target proteins for elucidating the associated molecular mechanisms of the interaction of host cellular proteins with viral proteins in regulating the viral replication.",2014 Jun 5,"['Wang, Li', 'Zhou, Lei', 'Zhang, Han', 'Li, Yan', 'Ge, Xinna', 'Guo, Xin', 'Yu, Kangzhen', 'Yang, Hanchun']",PLoS One,,,True
2557b13f557e15081960d49034d890a790943b38,PMC,Nonstructural Protein 5A Is Incorporated into Hepatitis C Virus Low-Density Particle through Interaction with Core Protein and Microtubules during Intracellular Transport,http://dx.doi.org/10.1371/journal.pone.0099022,PMC4048239,24905011,CC BY,"Nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) serves dual functions in viral RNA replication and virus assembly. Here, we demonstrate that HCV replication complex along with NS5A and Core protein was transported to the lipid droplet (LD) through microtubules, and NS5A-Core complexes were then transported from LD through early-to-late endosomes to the plasma membrane via microtubules. Further studies by cofractionation analysis and immunoelectron microscopy of the released particles showed that NS5A-Core complexes, but not NS4B, were present in the low-density fractions, but not in the high-density fractions, of the HCV RNA-containing virions and associated with the internal virion core. Furthermore, exosomal markers CD63 and CD81 were also detected in the low-density fractions, but not in the high-density fractions. Overall, our results suggest that HCV NS5A is associated with the core of the low-density virus particles which exit the cell through a preexisting endosome/exosome pathway and may contribute to HCV natural infection.",2014 Jun 6,"['Lai, Chao-Kuen', 'Saxena, Vikas', 'Tseng, Chung-Hsin', 'Jeng, King-Song', 'Kohara, Michinori', 'Lai, Michael M. C.']",PLoS One,,,True
60d68e4052a397966e72c6eda0895ca7d27afb68,PMC,Improving rheumatic fever surveillance in New Zealand: results of a surveillance sector review,http://dx.doi.org/10.1186/1471-2458-14-528,PMC4049392,24885018,CC BY,"BACKGROUND: The New Zealand (NZ) Government has made a strong commitment to reduce the incidence of rheumatic fever (RF) by two thirds, to 1.4 cases per 100,000, by mid-2017. We reviewed the NZ RF surveillance sector, aiming to identify potential improvements which would support optimal RF control and prevention activities. METHODS: This review used a recently developed surveillance sector review method. Interviews with 36 key informants were used to describe the sector, assess it and identify its gaps. Priorities for improvement and implementation strategies were determined following discussion with these key informants, with policy advisors and within the research team. RESULTS: Key improvements identified included the need for a comprehensive RF surveillance strategy, integrated reporting and an online national RF register. At a managerial level this review provided evidence for system change and built support for this across the surveillance sector. CONCLUSIONS: The surveillance sector review approach can be added to the small set of tools currently available for developing and evaluating surveillance systems. This new approach is likely to prove useful as we confront the challenges of combating new emerging infectious diseases, responding to global environmental changes, and reducing health inequalities.",2014 May 29,"['Oliver, Jane', 'Pierse, Nevil', 'Baker, Michael G']",BMC Public Health,,,True
bab3e74b5db5b2e04b521d1172b9df7726871aaa,PMC,Core Self-Evaluations Mediate the Associations of Dispositional Optimism and Life Satisfaction,http://dx.doi.org/10.1371/journal.pone.0097752,PMC4049581,24911367,CC BY,"BACKGROUND: Positive traits, such as life satisfaction, optimism, and core self-evaluation (CSE), have garnered increasing attention from researchers and professionals. However, the trilateral relationship among them remains unclear. OBJECTIVE: This study examines the effect of dispositional optimism on life satisfaction and primarily verified the mediator role of CSEs. METHODS: Six hundred thirty college students from two general universities completed a questionnaire packet containing life orientation test–revised (LOT–R), core self-evaluations, and satisfaction with life scale. Confirmatory factor analysis (CFA) was conducted to assess the dimension of LOT–R. Bootstrap was used in structural equation modeling to analyze mediation effect. RESULTS: Results revealed that dispositional optimism and core self-evaluations were significantly correlated with life satisfaction. CFA identified the bidimensional structure of dispositional optimism. SEM indicated that core self-evaluations partially mediated the effect of dispositional optimism on life satisfaction. The final model also revealed significant paths from optimism and pessimism to life satisfaction through core-self evaluations. CONCLUSION: The findings extended prior studies and shed light on how dispositional optimism influences life satisfaction. This study provides valuable evidence on how to promote the life satisfaction of human beings in positive psychology. A further study can fully explore the relationship among them in multi-cultural follow-up studies.",2014 Jun 9,"['Jiang, Wensheng', 'Li, Fei', 'Jiang, Haipeng', 'Yu, Lili', 'Liu, Wenbo', 'Li, Qiang', 'Zuo, Luning']",PLoS One,,,True
fbf214b2ff7bf5dc3d5dab6096d53cb086f0dea4,PMC,Estimated Effects of Projected Climate Change on the Basic Reproductive Number of the Lyme Disease Vector Ixodes scapularis,http://dx.doi.org/10.1289/ehp.1307799,PMC4050516,24627295,CC0,"Background: The extent to which climate change may affect human health by increasing risk from vector-borne diseases has been under considerable debate. Objectives: We quantified potential effects of future climate change on the basic reproduction number (R(0)) of the tick vector of Lyme disease, Ixodes scapularis, and explored their importance for Lyme disease risk, and for vector-borne diseases in general. Methods: We applied observed temperature data for North America and projected temperatures using regional climate models to drive an I. scapularis population model to hindcast recent, and project future, effects of climate warming on R(0). Modeled R(0) increases were compared with R(0) ranges for pathogens and parasites associated with variations in key ecological and epidemiological factors (obtained by literature review) to assess their epidemiological importance. Results: R(0) for I. scapularis in North America increased during the years 1971–2010 in spatio-temporal patterns consistent with observations. Increased temperatures due to projected climate change increased R(0) by factors (2–5 times in Canada and 1.5–2 times in the United States), comparable to observed ranges of R(0) for pathogens and parasites due to variations in strains, geographic locations, epidemics, host and vector densities, and control efforts. Conclusions: Climate warming may have co-driven the emergence of Lyme disease in northeastern North America, and in the future may drive substantial disease spread into new geographic regions and increase tick-borne disease risk where climate is currently suitable. Our findings highlight the potential for climate change to have profound effects on vectors and vector-borne diseases, and the need to refocus efforts to understand these effects. Citation: Ogden NH, Radojević M, Wu X, Duvvuri VR, Leighton PA, Wu J. 2014. Estimated effects of projected climate change on the basic reproductive number of the Lyme disease vector Ixodes scapularis. Environ Health Perspect 122:631–638; http://dx.doi.org/10.1289/ehp.1307799",2014 Jun 14,"['Ogden, Nicholas H.', 'Radojevic´, Milka', 'Wu, Xiaotian', 'Duvvuri, Venkata R.', 'Leighton, Patrick A.', 'Wu, Jianhong']",Environ Health Perspect,,,True
feccc27dc3c4100c8080abda883969ec979956c9,PMC,Estimated Effects of Projected Climate Change on the Basic Reproductive Number of the Lyme Disease Vector Ixodes scapularis,http://dx.doi.org/10.1289/ehp.1307799,PMC4050516,24627295,CC0,"Background: The extent to which climate change may affect human health by increasing risk from vector-borne diseases has been under considerable debate. Objectives: We quantified potential effects of future climate change on the basic reproduction number (R(0)) of the tick vector of Lyme disease, Ixodes scapularis, and explored their importance for Lyme disease risk, and for vector-borne diseases in general. Methods: We applied observed temperature data for North America and projected temperatures using regional climate models to drive an I. scapularis population model to hindcast recent, and project future, effects of climate warming on R(0). Modeled R(0) increases were compared with R(0) ranges for pathogens and parasites associated with variations in key ecological and epidemiological factors (obtained by literature review) to assess their epidemiological importance. Results: R(0) for I. scapularis in North America increased during the years 1971–2010 in spatio-temporal patterns consistent with observations. Increased temperatures due to projected climate change increased R(0) by factors (2–5 times in Canada and 1.5–2 times in the United States), comparable to observed ranges of R(0) for pathogens and parasites due to variations in strains, geographic locations, epidemics, host and vector densities, and control efforts. Conclusions: Climate warming may have co-driven the emergence of Lyme disease in northeastern North America, and in the future may drive substantial disease spread into new geographic regions and increase tick-borne disease risk where climate is currently suitable. Our findings highlight the potential for climate change to have profound effects on vectors and vector-borne diseases, and the need to refocus efforts to understand these effects. Citation: Ogden NH, Radojević M, Wu X, Duvvuri VR, Leighton PA, Wu J. 2014. Estimated effects of projected climate change on the basic reproductive number of the Lyme disease vector Ixodes scapularis. Environ Health Perspect 122:631–638; http://dx.doi.org/10.1289/ehp.1307799",2014 Jun 14,"['Ogden, Nicholas H.', 'Radojevic´, Milka', 'Wu, Xiaotian', 'Duvvuri, Venkata R.', 'Leighton, Patrick A.', 'Wu, Jianhong']",Environ Health Perspect,,,True
f719d2ff295ade18c5946296cd7c2436727d2822,PMC,Structural and functional characterization of MERS coronavirus papain-like protease,http://dx.doi.org/10.1186/1423-0127-21-54,PMC4051379,24898546,CC BY,"BACKGROUNDS: A new highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and Saudi Arabia and quickly spread to some European countries since September 2012. Until 15 May 2014, it has infected at least 572 people with a fatality rate of about 30% globally. Studies to understand the virus and to develop antiviral drugs or therapy are necessary and urgent. In the present study, MERS-CoV papain-like protease (PL(pro)) is expressed, and its structural and functional consequences are elucidated. RESULTS: Circular dichroism and Tyr/Trp fluorescence analyses indicated that the secondary and tertiary structure of MERS-CoV PL(pro) is well organized and folded. Analytical ultracentrifugation analyses demonstrated that MERS-CoV PL(pro) is a monomer in solution. The steady-state kinetic and deubiquitination activity assays indicated that MERS-CoV PL(pro) exhibits potent deubiquitination activity but lower proteolytic activity, compared with SARS-CoV PL(pro). A natural mutation, Leu105, is the major reason for this difference. CONCLUSIONS: Overall, MERS-CoV PL(pro) bound by an endogenous metal ion shows a folded structure and potent proteolytic and deubiquitination activity. These findings provide important insights into the structural and functional properties of coronaviral PL(pro) family, which is applicable to develop strategies inhibiting PL(pro) against highly pathogenic coronaviruses.",2014 Jun 4,"['Lin, Min-Han', 'Chuang, Shang-Ju', 'Chen, Chiao-Che', 'Cheng, Shu-Chun', 'Cheng, Kai-Wen', 'Lin, Chao-Hsiung', 'Sun, Chiao-Yin', 'Chou, Chi-Yuan']",J Biomed Sci,,,True
5a1718b5f9e6b1d39eab3363e7d49678ef87f1f9,PMC,Structural and functional characterization of MERS coronavirus papain-like protease,http://dx.doi.org/10.1186/1423-0127-21-54,PMC4051379,24898546,CC BY,"BACKGROUNDS: A new highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and Saudi Arabia and quickly spread to some European countries since September 2012. Until 15 May 2014, it has infected at least 572 people with a fatality rate of about 30% globally. Studies to understand the virus and to develop antiviral drugs or therapy are necessary and urgent. In the present study, MERS-CoV papain-like protease (PL(pro)) is expressed, and its structural and functional consequences are elucidated. RESULTS: Circular dichroism and Tyr/Trp fluorescence analyses indicated that the secondary and tertiary structure of MERS-CoV PL(pro) is well organized and folded. Analytical ultracentrifugation analyses demonstrated that MERS-CoV PL(pro) is a monomer in solution. The steady-state kinetic and deubiquitination activity assays indicated that MERS-CoV PL(pro) exhibits potent deubiquitination activity but lower proteolytic activity, compared with SARS-CoV PL(pro). A natural mutation, Leu105, is the major reason for this difference. CONCLUSIONS: Overall, MERS-CoV PL(pro) bound by an endogenous metal ion shows a folded structure and potent proteolytic and deubiquitination activity. These findings provide important insights into the structural and functional properties of coronaviral PL(pro) family, which is applicable to develop strategies inhibiting PL(pro) against highly pathogenic coronaviruses.",2014 Jun 4,"['Lin, Min-Han', 'Chuang, Shang-Ju', 'Chen, Chiao-Che', 'Cheng, Shu-Chun', 'Cheng, Kai-Wen', 'Lin, Chao-Hsiung', 'Sun, Chiao-Yin', 'Chou, Chi-Yuan']",J Biomed Sci,,,False
08885e2da682c5d027e986aacc166975e01fc60c,PMC,Lung ultrasound imaging in avian influenza A (H7N9) respiratory failure,http://dx.doi.org/10.1186/2036-7902-6-6,PMC4051407,24949191,CC BY,"BACKGROUND: Lung ultrasound has been shown to identify in real-time, various pathologies of the lung such as pneumonia, viral pneumonia, and acute respiratory distress syndrome (ARDS). Lung ultrasound maybe a first-line alternative to chest X-ray and CT scan in critically ill patients with respiratory failure. We describe the use of lung ultrasound imaging and findings in two cases of severe respiratory failure from avian influenza A (H7N9) infection. METHODS: Serial lung ultrasound images and video from two cases of H7N9 respiratory failure requiring mechanical ventilation and extracorporeal membrane oxygenation in a tertiary care intensive care unit were analyzed for characteristic lung ultrasound findings described previously for respiratory failure and infection. These findings were followed serially, correlated with clinical course and chest X-ray. RESULTS: In both patients, characteristic lung ultrasound findings have been observed as previously described in viral pulmonary infections: subpleural consolidations associated or not with local pleural effusion. In addition, numerous, confluent, or coalescing B-lines leading to ‘white lung’ with corresponding pleural line thickening are associated with ARDS. Extension or reduction of lesions observed with ultrasound was also correlated respectively with clinical worsening or improvement. Coexisting consolidated pneumonia with sonographic air bronchograms was noted in one patient who did not survive. CONCLUSIONS: Clinicians with access to point-of-care ultrasonography may use these findings as an alternative to chest X-ray or CT scan. Lung ultrasound imaging may assist in the efficient allocation of intensive care for patients with respiratory failure from viral pulmonary infections, especially in resource scarce settings or situations such as future respiratory virus outbreaks or pandemics.",2014 May 20,"['Tsai, Nga Wing', 'Ngai, Chun Wai', 'Mok, Ka Leung', 'Tsung, James W']",Crit Ultrasound J,,,True
6aa7ff7bbaba12fef375a84c5ba297d9f848541f,PMC,"NGS Nominated CELA1, HSPG2, and KCNK5 as Candidate Genes for Predisposition to Balkan Endemic Nephropathy",http://dx.doi.org/10.1155/2014/920723,PMC4052113,24949484,CC BY,"Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression leading to terminal renal failure. The results of molecular biological investigations propose that BEN is a multifactorial disease with genetic predisposition to environmental risk agents. Exome sequencing of 22 000 genes with Illumina Nextera Exome Enrichment Kit was performed on 22 DNA samples (11 Bulgarian patients and 11 Serbian patients). Software analysis was performed via NextGene, Provean, and PolyPhen. The frequency of all annotated genetic variants with deleterious/damaging effect was compared with those of European populations. Then we focused on nonannotated variants (with no data available about them and not found in healthy Bulgarian controls). There is no statistically significant difference between annotated variants in BEN patients and European populations. From nonannotated variants with more than 40% frequency in both patients' groups, we nominated 3 genes with possible deleterious/damaging variants—CELA1, HSPG2, and KCNK5. Mutant genes (CELA1, HSPG2, and KCNK5) in BEN patients encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis. We suggest that an abnormal process of angiogenesis plays a key role in the molecular pathogenesis of BEN.",2014 May 15,"['Toncheva, D.', 'Mihailova-Hristova, M.', 'Vazharova, R.', 'Staneva, R.', 'Karachanak, S.', 'Dimitrov, P.', 'Simeonov, V.', 'Ivanov, S.', 'Balabanski, L.', 'Serbezov, D.', 'Malinov, M.', 'Stefanovic, V.', 'Čukuranović, R.', 'Polenakovic, M.', 'Jankovic-Velickovic, L.', 'Djordjevic, V.', 'Jevtovic-Stoimenov, T.', 'Plaseska-Karanfilska, D.', 'Galabov, A.', 'Djonov, V.', 'Dimova, I.']",Biomed Res Int,,,True
bdd49a68f33046aa3a724721b7050c5f548f90de,PMC,Identification of Plakortide E from the Caribbean Sponge Plakortis halichondroides as a Trypanocidal Protease Inhibitor using Bioactivity-Guided Fractionation,http://dx.doi.org/10.3390/md12052614,PMC4052307,24798927,CC BY,"In this paper, we report new protease inhibitory activity of plakortide E towards cathepsins and cathepsin-like parasitic proteases. We further report on its anti-parasitic activity against Trypanosoma brucei with an IC(50) value of 5 μM and without cytotoxic effects against J774.1 macrophages at 100 μM concentration. Plakortide E was isolated from the sponge Plakortis halichondroides using enzyme assay-guided fractionation and identified by NMR spectroscopy and mass spectrometry. Furthermore, enzyme kinetic studies confirmed plakortide E as a non-competitive, slowly-binding, reversible inhibitor of rhodesain.",2014 May 2,"['Oli, Swarna', 'Abdelmohsen, Usama Ramadan', 'Hentschel, Ute', 'Schirmeister, Tanja']",Mar Drugs,,,True
a81118016cd86948665a49c7562f577f83cb87b5,PMC,"Response surface modeling for hot, humid air decontamination of materials contaminated with Bacillus anthracis ∆Sterne and Bacillus thuringiensis Al Hakam spores",http://dx.doi.org/10.1186/s13568-014-0021-3,PMC4052701,24949256,CC BY,"Response surface methodology using a face-centered cube design was used to describe and predict spore inactivation of Bacillus anthracis ∆Sterne and Bacillus thuringiensis Al Hakam spores after exposure of six spore-contaminated materials to hot, humid air. For each strain/material pair, an attempt was made to fit a first or second order model. All three independent predictor variables (temperature, relative humidity, and time) were significant in the models except that time was not significant for B. thuringiensis Al Hakam on nylon. Modeling was unsuccessful for wiring insulation and wet spores because there was complete spore inactivation in the majority of the experimental space. In cases where a predictive equation could be fit, response surface plots with time set to four days were generated. The survival of highly purified Bacillus spores can be predicted for most materials tested when given the settings for temperature, relative humidity, and time. These predictions were cross-checked with spore inactivation measurements.",2014 May 1,"['Prokop, Edward J', 'Crigler, John R', 'Wells, Claire M', 'Young, Alice A', 'Buhr, Tony L']",AMB Express,,,True
bc1d2578b23ef87c23e94bb11bf4986606483527,PMC,Conflicts of Interest during Contact Investigations: A Game-Theoretic Analysis,http://dx.doi.org/10.1155/2014/952381,PMC4052784,24982688,CC BY,"The goal of contact tracing is to reduce the likelihood of transmission, particularly to individuals who are at greatest risk for developing complications of infection, as well as identifying individuals who are in need of medical treatment of other interventions. In this paper, we develop a simple mathematical model of contact investigations among a small group of individuals and apply game theory to explore conflicts of interest that may arise in the context of perceived costs of disclosure. Using analytic Kolmogorov equations, we determine whether or not it is possible for individual incentives to drive noncooperation, even though cooperation would yield a better group outcome. We found that if all individuals have a cost of disclosure, then the optimal individual decision is to simply not disclose each other. With further analysis of (1) completely offsetting the costs of disclosure and (2) partially offsetting the costs of disclosure, we found that all individuals disclose all contacts, resulting in a smaller basic reproductive number and an alignment of individual and group optimality. More data are needed to understand decision making during outbreak investigations and what the real and perceived costs are.",2014 Apr 14,"['Sippl-Swezey, Nicolas', 'Enanoria, Wayne T.', 'Porco, Travis C.']",Comput Math Methods Med,,,True
ce6af0bb9b796bf3ddc44ddabdce04a7584957d5,PMC,Antiviral activity and possible mode of action of ellagic acid identified in Lagerstroemia speciosa leaves toward human rhinoviruses,http://dx.doi.org/10.1186/1472-6882-14-171,PMC4052798,24885569,CC BY,"BACKGROUND: Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cause billions of USD annually in medical visits and school and work absenteeism. An assessment was made of the cytotoxic and antiviral activities and possible mode of action of the tannin ellagic acid from the leaves of Lagerstroemia speciosa toward HeLa cells and three rhinoviruses, HRV-2, -3, and -4. METHODS: The antiviral property and mechanism of action of ellagic acid were evaluated using a sulforhodamine B assay and real-time reverse transcription-PCR (RT-PCR) with SYBR Green dye. Results were compared with those of the currently used broad-spectrum antiviral agent, ribavirin. RESULTS: As judged by 50% inhibitory concentration values, natural ellagic acid was 1.8, 2.3, and 2.2 times more toxic toward HRV-2 (38 μg/mL), HRV-3 (31 μg/mL), and HRV-4 (29 μg/mL) than ribavirin, respectively. The inhibition rate of preincubation with 50 μg/mL ellagic acid was 17%, whereas continuous presence of ellagic acid during infection led to a significant increase in the inhibition (70%). Treatment with 50 μg/mL ellagic acid considerably suppressed HRV-4 infection only when added just after the virus inoculation (0 h) (87% inhibition), but not before -1 h or after 1 h or later (<20% inhibition). These findings suggest that ellagic acid does not interact with the HRV-4 particles and may directly interact with the human cells in the early stage of HRV infections to protect the cells from the virus destruction. Furthermore, RT-PCR analysis revealed that 50 μg/mL ellagic acid strongly inhibited the RNA replication of HRV-4 in HeLa cells, suggesting that ellagic acid inhibits virus replication by targeting on cellular molecules, rather than virus molecules. CONCLUSIONS: Global efforts to reduce the level of antibiotics justify further studies on L. speciosa leaf-derived materials containing ellagic acid as potential anti-HRV products or a lead molecule for the prevention or treatment of HRV infection.",2014 May 26,"['Park, Sang Wook', 'Kwon, Min Jung', 'Yoo, Ji Young', 'Choi, Hwa-Jung', 'Ahn, Young-Joon']",BMC Complement Altern Med,,,True
fdf03dcd427aa029a6b213288a7e862519decafb,PMC,Glycyrrhizic Acid in the Treatment of Liver Diseases: Literature Review,http://dx.doi.org/10.1155/2014/872139,PMC4052927,24963489,CC BY,"Glycyrrhizic acid (GA) is a triterpene glycoside found in the roots of licorice plants (Glycyrrhiza glabra). GA is the most important active ingredient in the licorice root, and possesses a wide range of pharmacological and biological activities. GA coupled with glycyrrhetinic acid and 18-beta-glycyrrhetic acid was developed in China or Japan as an anti-inflammatory, antiviral, and antiallergic drug for liver disease. This review summarizes the current biological activities of GA and its medical applications in liver diseases. The pharmacological actions of GA include inhibition of hepatic apoptosis and necrosis; anti-inflammatory and immune regulatory actions; antiviral effects; and antitumor effects. This paper will be a useful reference for physicians and biologists researching GA and will open the door to novel agents in drug discovery and development from Chinese herbs. With additional research, GA may be more widely used in the treatment of liver diseases or other conditions.",2014 May 13,"['Li, Jian-yuan', 'Cao, Hong-yan', 'Liu, Ping', 'Cheng, Gen-hong', 'Sun, Ming-yu']",Biomed Res Int,,,True
c42f9e96fcbb25a8f456fb17af3d591c1300ae64,PMC,RIG-I Enhanced Interferon Independent Apoptosis upon Junin Virus Infection,http://dx.doi.org/10.1371/journal.pone.0099610,PMC4053358,24918927,CC BY,"Junin virus (JUNV) is the etiological agent of Argentine hemorrhagic fever (AHF), a human disease with a high case-fatality rate. It is widely accepted that arenaviral infections, including JUNV infections, are generally non-cytopathic. In contrast, here we demonstrated apoptosis induction in human lung epithelial carcinoma (A549), human hepatocarcinoma and Vero cells upon infection with the attenuated Candid#1 strain of, JUNV as determined by phosphatidylserine (PS) translocation, Caspase 3 (CASP3) activation, Poly (ADP-ribose) polymerase (PARP) cleavage and/or chromosomal DNA fragmentation. Moreover, as determined by DNA fragmentation, we found that the pathogenic Romero strain of JUNV was less cytopathic than Candid#1 in human hepatocarcinoma and Vero, but more apoptotic in A549 and Vero E6 cells. Additionally, we found that JUNV-induced apoptosis was enhanced by RIG-I signaling. Consistent with the previously reported role of RIG-I like helicase (RLH) signaling in initiating programmed cell death, we showed that cell death or DNA fragmentation of Candid#1-infected A549 cells was decreased upon siRNA or shRNA silencing of components of RIG-I pathway in spite of increased virus production. Similarly, we observed decreased DNA fragmentation in JUNV-infected human hepatocarcinoma cells deficient for RIG-I when compared with that of RIG-I-competent cells. In addition, DNA fragmentation detected upon Candid#1 infection of type I interferon (IFN)-deficient Vero cells suggested a type I IFN-independent mechanism of apoptosis induction in response to JUNV. Our work demonstrated for the first time apoptosis induction in various cells of mammalian origin in response to JUNV infection and partial mechanism of this cell death.",2014 Jun 11,"['Kolokoltsova, Olga A.', 'Grant, Ashley M.', 'Huang, Cheng', 'Smith, Jennifer K.', 'Poussard, Allison L.', 'Tian, Bing', 'Brasier, Allan R.', 'Peters, Clarence J.', 'Tseng, Chien-Te Kent', 'de la Torre, Juan C.', 'Paessler, Slobodan']",PLoS One,,,True
f9075b3b2fcb919dd92b981ac6161302c5f904cd,PMC,Targeting IL-1β and IL-17A Driven Inflammation during Influenza-Induced Exacerbations of Chronic Lung Inflammation,http://dx.doi.org/10.1371/journal.pone.0098440,PMC4053370,24918427,CC BY,"For patients with chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), exacerbations are life-threatening events causing acute respiratory distress that can even lead to hospitalization and death. Although a great deal of effort has been put into research of exacerbations and potential treatment options, the exact underlying mechanisms are yet to be deciphered and no therapy that effectively targets the excessive inflammation is available. In this study, we report that interleukin-1β (IL-1β) and interleukin-17A (IL-17A) are key mediators of neutrophilic inflammation in influenza-induced exacerbations of chronic lung inflammation. Using a mouse model of disease, our data shows a role for IL-1β in mediating lung dysfunction, and in driving neutrophilic inflammation during the whole phase of viral infection. We further report a role for IL-17A as a mediator of IL-1β induced neutrophilia at early time points during influenza-induced exacerbations. Blocking of IL-17A or IL-1 resulted in a significant abrogation of neutrophil recruitment to the airways in the initial phase of infection or at the peak of viral replication, respectively. Therefore, IL-17A and IL-1β are potential targets for therapeutic treatment of viral exacerbations of chronic lung inflammation",2014 Jun 11,"['Sichelstiel, Anke', 'Yadava, Koshika', 'Trompette, Aurélien', 'Salami, Olawale', 'Iwakura, Yoichiro', 'Nicod, Laurent P.', 'Marsland, Benjamin J.']",PLoS One,,,True
63f9ef8701b8b68aab585d81fa58bd567ade8e4a,PMC,Critical role of cellular cholesterol in bovine rotavirus infection,http://dx.doi.org/10.1186/1743-422X-11-98,PMC4053397,24884772,CC BY,"BACKGROUND: Bovine rotavirus (BRV) is a non-enveloped dsRNA virus that cause neonatal calf diarrhea. Lipid rafts are cholesterol-enrich membrane mircodomains that play a vital role in many cellular processes. In this study, the effect of cellular cholesterol depletion on infection of MA-104 cells with bovine rotavirus was investigated. RESULTS: We demonstrated that cholesterol depletion of the plasma membrane by MβCD had no effect on BRV binding to cells but significantly impaired BRV entry in a dose-dependent manner and the effect was partially reversed by addition of exogenous cholesterol, suggesting the reduction of BRV infection by MβCD was specifically due to cholesterol depletion. Cholesterol depletion after virus entry did not reduce BRV replication, whereas affected virus assembly. CONCLUSIONS: Taken together, our results demonstrate that cell membrane cholesterol is essential to BRV infectivity.",2014 May 23,"['Cui, Jin', 'Fu, Xinliang', 'Xie, Jiexiong', 'Gao, Ming', 'Hong, Malin', 'Chen, Yao', 'Su, Shuo', 'Li, Shoujun']",Virol J,,,True
76e0bd45995e7799e0f52be915f66719e24265a9,PMC,Pharmacokinetics of Anti-HBV Polyoxometalate in Rats,http://dx.doi.org/10.1371/journal.pone.0098292,PMC4055585,24921932,CC BY,"Polyoxometalates are non-nucleoside analogs that have been proven to exhibit broad-spectrum antiviral activity. In particular, Cs(2)K(4)Na[SiW(9)Nb(3)O(40)].H(2)O 1 shows low toxicity and high activity against HBV. The preclinical pharmacokinetics of Compound 1 in rats were characterized by establishing and applying inductively coupled plasma-mass spectrometry method to determine the concentration of W in plasma, urine, feces, bile and organ samples. The quantitative ICP-MS method demonstrated good sensitivity and application in the pharmacokinetics study of polyoxometalates. The pharmacokinetic behavior of Compound 1 after intravenous or oral administration fit a two-compartment model. T(max) ranges from 0.1 h to 3 h and the T(1/2) of Compound 1 is between 20 h and 30 h. The absolute bioavailability of Compound 1 at 45, 180 and 720 mg/kg groups were 23.68%, 14.67% and 11.93%, respectively. The rates of plasma protein binding of Compound 1 at 9, 18 and 36 mg/ml of Compound 1 are 62.13±9.41%, 71.20±24.98% and 49.00±25.59%, respectively. Compound 1 was widely distributed throughout the body, and high levels of compound 1 were found in the kidney and liver. The level of Compound 1 in excretion was lower: 30% for urine, 0.28% for feces and 0.42% for bile, respectively. For elaborate pharmacokinetic characteristics to be fully understood, the metabolism of Compound 1 needs to be studied further.",2014 Jun 12,"['Wang, Juan', 'Qu, Xiaofeng', 'Qi, Yanfei', 'Li, Jinhua', 'Song, Xiuling', 'Li, Li', 'Yin, Dehui', 'Xu, Kun', 'Li, Juan']",PLoS One,,,True
d400825a1ea10fb8d5bdbc96b2c00e866eb75f1d,PMC,Equine Arteritis Virus Does Not Induce Interferon Production in Equine Endothelial Cells: Identification of Nonstructural Protein 1 as a Main Interferon Antagonist,http://dx.doi.org/10.1155/2014/420658,PMC4055586,24967365,CC BY,"The objective of this study was to investigate the effect of equine arteritis virus (EAV) on type I interferon (IFN) production. Equine endothelial cells (EECs) were infected with the virulent Bucyrus strain (VBS) of EAV and expression of IFN-β was measured at mRNA and protein levels by quantitative real-time RT-PCR and IFN bioassay using vesicular stomatitis virus expressing the green fluorescence protein (VSV-GFP), respectively. Quantitative RT-PCR results showed that IFN-β mRNA levels in EECs infected with EAV VBS were not increased compared to those in mock-infected cells. Consistent with quantitative RT-PCR, Sendai virus- (SeV-) induced type I IFN production was inhibited by EAV infection. Using an IFN-β promoter-luciferase reporter assay, we subsequently demonstrated that EAV nsps 1, 2, and 11 had the capability to inhibit type I IFN activation. Of these three nsps, nsp1 exhibited the strongest inhibitory effect. Taken together, these data demonstrate that EAV has the ability to suppress the type I IFN production in EECs and nsp1 may play a critical role to subvert the equine innate immune response.",2014 May 25,"['Go, Yun Young', 'Li, Yanhua', 'Chen, Zhenhai', 'Han, Mingyuan', 'Yoo, Dongwan', 'Fang, Ying', 'Balasuriya, Udeni B. R.']",Biomed Res Int,,,True
daa3f7d4838adebf0aac1be3cda2924fc1d2106a,PMC,Circulating Levels of Tumor Necrosis Factor-Alpha Receptor 2 Are Increased in Heart Failure with Preserved Ejection Fraction Relative to Heart Failure with Reduced Ejection Fraction: Evidence for a Divergence in Pathophysiology,http://dx.doi.org/10.1371/journal.pone.0099495,PMC4055721,24923671,CC BY,"BACKGROUND: Various pathways have been implicated in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFPEF). Inflammation in response to comorbid conditions, such as hypertension and diabetes, may play a proportionally larger role in HFPEF as compared to HF with reduced ejection fraction (HFREF). METHODS AND RESULTS: This study investigated inflammation mediated by the tumor necrosis factor-alpha (TNFα) axis in community-based cohorts of HFPEF patients (n = 100), HFREF patients (n = 100) and healthy controls (n = 50). Enzyme-linked immunosorbent assays were used to investigate levels of TNFα, its two receptors (TNFR1 and TNFR2), and a non-TNFα cytokine, interleukin-6 (IL-6), in plasma derived from peripheral blood samples. Plasma levels of TNFα and TNFR1 were significantly elevated in HFPEF relative to controls, while levels of TNFR2 were significantly higher in HFPEF than both controls and HFREF. TNFα, TNFR1 and TNFR2 were each significantly associated with at least two of the following: age, estimated glomerular filtration rate, hypertension, diabetes, smoking, peripheral vascular disease or history of atrial fibrillation. TNFR2 levels were also significantly associated with increasing grade of diastolic dysfunction and severity of symptoms in HFPEF. CONCLUSIONS: Inflammation mediated through TNFα and its receptors, TNFR1 and TNFR2, may represent an important component of a comorbidity-induced inflammatory response that partially drives the pathophysiology of HFPEF.",2014 Jun 12,"['Putko, Brendan N.', 'Wang, Zuocheng', 'Lo, Jennifer', 'Anderson, Todd', 'Becher, Harald', 'Dyck, Jason R. B.', 'Kassiri, Zamaneh', 'Oudit, Gavin Y.', None]",PLoS One,,,True
4cd3f43501d49e775838473a3edafb55e57d08df,PMC,Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1004192,PMC4055766,24945244,CC BY,"Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype often cause severe pneumonia and multiple organ failure in humans, with reported case fatality rates of more than 60%. To develop a clinical antibody therapy, we generated a human-mouse chimeric monoclonal antibody (MAb) ch61 that showed strong neutralizing activity against H5N1 HPAI viruses isolated from humans and evaluated its protective potential in mouse and nonhuman primate models of H5N1 HPAI virus infections. Passive immunization with MAb ch61 one day before or after challenge with a lethal dose of the virus completely protected mice, and partial protection was achieved when mice were treated 3 days after the challenge. In a cynomolgus macaque model, reduced viral loads and partial protection against lethal infection were observed in macaques treated with MAb ch61 intravenously one and three days after challenge. Protective effects were also noted in macaques under immunosuppression. Though mutant viruses escaping from neutralization by MAb ch61 were recovered from macaques treated with this MAb alone, combined treatment with MAb ch61 and peramivir reduced the emergence of escape mutants. Our results indicate that antibody therapy might be beneficial in reducing viral loads and delaying disease progression during H5N1 HPAI virus infection in clinical cases and combined treatment with other antiviral compounds should improve the protective effects of antibody therapy against H5N1 HPAI virus infection.",2014 Jun 12,"['Itoh, Yasushi', 'Yoshida, Reiko', 'Shichinohe, Shintaro', 'Higuchi, Megumi', 'Ishigaki, Hirohito', 'Nakayama, Misako', 'Pham, Van Loi', 'Ishida, Hideaki', 'Kitano, Mitsutaka', 'Arikata, Masahiko', 'Kitagawa, Naoko', 'Mitsuishi, Yachiyo', 'Ogasawara, Kazumasa', 'Tsuchiya, Hideaki', 'Hiono, Takahiro', 'Okamatsu, Masatoshi', 'Sakoda, Yoshihiro', 'Kida, Hiroshi', 'Ito, Mutsumi', 'Quynh Mai, Le', 'Kawaoka, Yoshihiro', 'Miyamoto, Hiroko', 'Ishijima, Mari', 'Igarashi, Manabu', 'Suzuki, Yasuhiko', 'Takada, Ayato']",PLoS Pathog,,,True
f82005e7a19bb8a9a23d6d2d4ce3b5dd18c7d26e,PMC,Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1004192,PMC4055766,24945244,CC BY,"Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype often cause severe pneumonia and multiple organ failure in humans, with reported case fatality rates of more than 60%. To develop a clinical antibody therapy, we generated a human-mouse chimeric monoclonal antibody (MAb) ch61 that showed strong neutralizing activity against H5N1 HPAI viruses isolated from humans and evaluated its protective potential in mouse and nonhuman primate models of H5N1 HPAI virus infections. Passive immunization with MAb ch61 one day before or after challenge with a lethal dose of the virus completely protected mice, and partial protection was achieved when mice were treated 3 days after the challenge. In a cynomolgus macaque model, reduced viral loads and partial protection against lethal infection were observed in macaques treated with MAb ch61 intravenously one and three days after challenge. Protective effects were also noted in macaques under immunosuppression. Though mutant viruses escaping from neutralization by MAb ch61 were recovered from macaques treated with this MAb alone, combined treatment with MAb ch61 and peramivir reduced the emergence of escape mutants. Our results indicate that antibody therapy might be beneficial in reducing viral loads and delaying disease progression during H5N1 HPAI virus infection in clinical cases and combined treatment with other antiviral compounds should improve the protective effects of antibody therapy against H5N1 HPAI virus infection.",2014 Jun 12,"['Itoh, Yasushi', 'Yoshida, Reiko', 'Shichinohe, Shintaro', 'Higuchi, Megumi', 'Ishigaki, Hirohito', 'Nakayama, Misako', 'Pham, Van Loi', 'Ishida, Hideaki', 'Kitano, Mitsutaka', 'Arikata, Masahiko', 'Kitagawa, Naoko', 'Mitsuishi, Yachiyo', 'Ogasawara, Kazumasa', 'Tsuchiya, Hideaki', 'Hiono, Takahiro', 'Okamatsu, Masatoshi', 'Sakoda, Yoshihiro', 'Kida, Hiroshi', 'Ito, Mutsumi', 'Quynh Mai, Le', 'Kawaoka, Yoshihiro', 'Miyamoto, Hiroko', 'Ishijima, Mari', 'Igarashi, Manabu', 'Suzuki, Yasuhiko', 'Takada, Ayato']",PLoS Pathog,,,False
049d30dbc331c7fd67ee83bed3990804272155b0,PMC,Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1004192,PMC4055766,24945244,CC BY,"Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype often cause severe pneumonia and multiple organ failure in humans, with reported case fatality rates of more than 60%. To develop a clinical antibody therapy, we generated a human-mouse chimeric monoclonal antibody (MAb) ch61 that showed strong neutralizing activity against H5N1 HPAI viruses isolated from humans and evaluated its protective potential in mouse and nonhuman primate models of H5N1 HPAI virus infections. Passive immunization with MAb ch61 one day before or after challenge with a lethal dose of the virus completely protected mice, and partial protection was achieved when mice were treated 3 days after the challenge. In a cynomolgus macaque model, reduced viral loads and partial protection against lethal infection were observed in macaques treated with MAb ch61 intravenously one and three days after challenge. Protective effects were also noted in macaques under immunosuppression. Though mutant viruses escaping from neutralization by MAb ch61 were recovered from macaques treated with this MAb alone, combined treatment with MAb ch61 and peramivir reduced the emergence of escape mutants. Our results indicate that antibody therapy might be beneficial in reducing viral loads and delaying disease progression during H5N1 HPAI virus infection in clinical cases and combined treatment with other antiviral compounds should improve the protective effects of antibody therapy against H5N1 HPAI virus infection.",2014 Jun 12,"['Itoh, Yasushi', 'Yoshida, Reiko', 'Shichinohe, Shintaro', 'Higuchi, Megumi', 'Ishigaki, Hirohito', 'Nakayama, Misako', 'Pham, Van Loi', 'Ishida, Hideaki', 'Kitano, Mitsutaka', 'Arikata, Masahiko', 'Kitagawa, Naoko', 'Mitsuishi, Yachiyo', 'Ogasawara, Kazumasa', 'Tsuchiya, Hideaki', 'Hiono, Takahiro', 'Okamatsu, Masatoshi', 'Sakoda, Yoshihiro', 'Kida, Hiroshi', 'Ito, Mutsumi', 'Quynh Mai, Le', 'Kawaoka, Yoshihiro', 'Miyamoto, Hiroko', 'Ishijima, Mari', 'Igarashi, Manabu', 'Suzuki, Yasuhiko', 'Takada, Ayato']",PLoS Pathog,,,False
9e102fc4487f4b9cdc7f7426ad24ba33aa1a4d42,PMC,Immune derangement occurs in patients with H7N9 avian influenza,http://dx.doi.org/10.1186/cc13788,PMC4056113,25030090,CC BY,"INTRODUCTION: Currently, little is known about the immunological characteristics of patients with avian influenza A (H7N9) virus infection. METHODS: The numbers and percentages of peripheral blood immune cells were measured in 27 patients with laboratory-confirmed H7N9 virus infection and 30 healthy controls (HCs). The functional phenotypes of T cells and monocytes, as well as serum cytokine levels, were analyzed by flow cytometry. RESULTS: There were 19 patients (70.4%) with acute respiratory distress syndrome, 13 (48.1%) with secondary respiratory infection, 20 (74%) with systemic inflammatory response syndrome (SIRS; defined as having at least two concurrent SIRS components), 18 (66.7%) with lymphocytopenia and 11 (40.7%) with reduced numbers of monocytes. In comparison with levels in the HCs, the levels of serum interleukin 6 (IL-6), IL-8 and IL-10 and the percentages of CD38+ or Tim-3+ T cells were significantly increased. However, the percentages of human leukocyte antigen-DR + and Tim-3+ monocytes were significantly decreased in patients compared with HCs. CONCLUSIONS: Patients with avian H7N9 virus infection display profound SIRS concomitantly with an anti-inflammatory response, which may be associated with the rapid progression of and high mortality associated with this novel viral disease.",2014 Mar 24,"['Wu, Wei', 'Shi, Yu', 'Gao, Hainv', 'Liang, Weifeng', 'Sheng, Jifang', 'Li, Lanjuan']",Crit Care,,,True
f6d6d7efc1686a7d219ecfc55f9a48ce72d4fb00,PMC,Genome Sequences of Porcine Epidemic Diarrhea Virus: In Vivo and In Vitro Phenotypes,http://dx.doi.org/10.1128/genomeA.00503-14,PMC4056290,24926047,CC BY,"Since the outbreak of porcine epidemic diarrhea virus (PEDV) in May 2013, U.S. swine producers have lost almost five million baby pigs. In an attempt to understand the evolution of PEDV in the United States and possibly develop a control strategy, we compared the genome sequences of a PEDV strain isolated from an infected piglet against its in vitro adapted version. The original PEDV strain was grown in Vero cells and passed 10 times serially in a MARC145 cell line. The sequence analysis of the native PEDV strain and in vitro passaged virus shows that the cell culture adaptation specifically modifies PEDV spike protein whereas the open reading frame 1a/b (ORF1a/b)-encoded polyprotein, the nucleoprotein, NS3B (ORF3), and membrane and envelope proteins remain unchanged.",2014 Jun 12,"['Lawrence, Paulraj K.', 'Bumgardner, Eric', 'Bey, Russell F.', 'Stine, Douglas', 'Bumgarner, Roger E.']",Genome Announc,,,True
6ebb0d128a1f03635f662f5419927c90c61855e5,PMC,Activation of JNK1/2 and p38 MAPK signaling pathways promotes enterovirus 71 infection in immature dendritic cells,http://dx.doi.org/10.1186/1471-2180-14-147,PMC4057572,24906853,CC BY,"BACKGROUND: c-Jun NH(2)-terminal kinase/stress-activated kinase (JNK/SAPK) and the p38 mitogen-activated protein kinase (p38 MAPK) are important components of cellular signal transduction pathways, which have been reported to be involved in viral replication. However, little is known about JNK1/2 and p38 MAPK signaling pathways in enterovirus 71 (EV71)-infected immature dendritic cells (iDCs). Thus, iDCs were induced from peripheral blood mononuclear cells (PBMC) and performed to explore the expressions and phosphorylation of molecules in the two signaling pathways as well as secretions of inflammatory cytokines and interferons during EV71 replication. RESULTS: We showed that EV71 infection could activate both JNK1/2 and p38 MAPK in iDCs and phosphorylate their downstream transcription factors c-Fos and c-Jun, which further promoted the production of IL-2, IL-6, IL-10, and TNF-α. Moreover, EV71 infection also increased the release of IFN-β and IL-12 p40. Pretreatment of iDCs with SP600125 and SB203580 (20 μM) could severely impair viral replication and its induced phosphorylation of JNK1/2,p38 MAPK, c-Fos and c-Jun. In addition, treatment of EV71-infected iDCs with SP600125 and SB203580 could inhibit secretions of IL-6, IL-10 and TNF-α. CONCLUSION: JNK1/2 and p38 MAPK signaling pathways are beneficial to EV71 infection and positively regulate secretions of inflammatory cytokines in iDCs.",2014 Jun 7,"['Peng, Hongjun', 'Shi, Mei', 'Zhang, Li', 'Li, Yuanyuan', 'Sun, Jing', 'Zhang, Lirong', 'Wang, Xiaohui', 'Xu, Xiaopeng', 'Zhang, Xiaolei', 'Mao, Yijie', 'Ji, Yun', 'Jiang, Jingting', 'Shi, Weifeng']",BMC Microbiol,,,True
55f79ab7db345d29089af0c330d95292350ba225,PMC,Influenza and other respiratory virus infections in outpatients with medically attended acute respiratory infection during the 2011-12 influenza season,http://dx.doi.org/10.1111/irv.12247,PMC4057994,24852890,CC BY,"BACKGROUND: Respiratory tract infections are a major cause of outpatient visits, yet only a portion is tested to determine the etiologic organism. Multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) assays for detection of multiple viruses are being used increasingly in clinical settings. METHODS: During January–April 2012, outpatients with acute respiratory illness (≤7 days) were tested for influenza using singleplex RT-PCR (SRT-PCR). A subset was assayed for 18 viruses using MRT-PCR to compare detection of influenza and examine the distribution of viruses and characteristics of patients using multinomial logistic regression. RESULTS: Among 662 participants (6 months–82 years), detection of influenza was similar between the MRT-PCR and SRT-PCR (κ = 0·83). No virus was identified in 267 (40.3%) samples. Commonly detected viruses were human rhinovirus (HRV, 15·4%), coronavirus (CoV, 10·4%), respiratory syncytial virus (RSV, 8·4%), human metapneumovirus (hMPV, 8·3%), and influenza (6%). Co-detections were infrequent (6·9%) and most commonly occurred among those <18 years old. In regression analyses, compared with non-viral illnesses, RSV and hMPV were significantly more frequent in children and less frequent in 18- to 49-year-olds than in those ≥50 years (P = 0·01), fever was more common in hMPV and influenza infections (P = 0·008), nasal congestion was more frequent in CoV, HRV, hMPV, influenza and RSV infections (P = 0·001), and body mass index was higher among those with influenza (P = 0·036). CONCLUSIONS: Using MRT-PCR, a viral etiology was found in three-fifths of patients with medically attended outpatient visits for acute respiratory illness during the influenza season; co-detected viruses were infrequent. Symptoms varied by viral etiology.",2014 Jul 8,"['Zimmerman, Richard K', 'Rinaldo, Charles R', 'Nowalk, Mary Patricia', 'GK, Balasubramani', 'Thompson, Mark G', 'Moehling, Krissy K', 'Bullotta, Arlene', 'Wisniewski, Stephen']",Influenza Other Respir Viruses,,,True
93f8a441807d1356ad516a8681e14fc093ab016b,PMC,Methods To Identify Aptamers against Cell Surface Biomarkers,http://dx.doi.org/10.3390/ph4091216,PMC4058655,,CC BY,"Aptamers are nucleic acid-based ligands identified through a process of molecular evolution named SELEX (Systematic Evolution of Ligands by Exponential enrichment). During the last 10-15 years, numerous aptamers have been developed specifically against targets present on or associated with the surface of human cells or infectious pathogens such as viruses, bacteria, fungi or parasites. Several of the aptamers have been described as potent probes, rivalling antibodies, for use in flow cytometry or microscopy. Some have also been used as drugs by inhibiting or activating functions of their targets in a manner similar to neutralizing or agonistic antibodies. Additionally, it is straightforward to conjugate aptamers to other agents without losing their affinity and they have successfully been used in vitro and in vivo to deliver drugs, siRNA, nanoparticles or contrast agents to target cells. Hence, aptamers identified against cell surface biomarkers represent a promising class of ligands. This review presents the different strategies of SELEX that have been developed to identify aptamers for cell surface-associated proteins as well as some of the methods that are used to study their binding on living cells.",2011 Sep 19,"['Cibiel, Agnes', 'Dupont, Daniel Miotto', 'Ducongé, Frédéric']",Pharmaceuticals (Basel),,,True
9d16d9dcd360578447fca314b4f8b873b23acf0b,PMC,Echinacea—A Source of Potent Antivirals for Respiratory Virus Infections,http://dx.doi.org/10.3390/ph4071019,PMC4058675,,CC BY,"Extracts of Echinacea species have been used traditionally in North America for the control of symptoms of colds, influenza, and other diseases, and some of them have become very popular as “herbal medicines”. Recent studies have revealed that preparations derived from certain species and plant parts, but not all of them, possess potent antiviral activities, at non-cytotoxic concentrations, particularly against membrane-containing viruses. Thus all strains of human and avian influenza viruses tested (including a Tamiflu-resistant strain), as well as herpes simplex virus, respiratory syncytial virus, and rhinoviruses, were very sensitive to a standardized Echinacea purpurea preparation. In mechanistic studies the influenza virus-specific hemagglutinin and neuraminidase were inhibited. In addition some extracts displayed anti-inflammatory activity in virus-infected cells, and numerous other effects on the expression of cellular genes. Multiple components, either discrete compounds or mixtures, appeared to be responsible for the various antiviral activities.",2011 Jul 13,"['Hudson, James', 'Vimalanathan, Selvarani']",Pharmaceuticals (Basel),,,True
a65d8f4193a3b03c5d20fac1972e0756ecf2d328,PMC,Clinical Disease Severity of Respiratory Viral Co-Infection versus Single Viral Infection: A Systematic Review and Meta-Analysis,http://dx.doi.org/10.1371/journal.pone.0099392,PMC4059637,24932493,CC BY,"BACKGROUND: Results from cohort studies evaluating the severity of respiratory viral co-infections are conflicting. We conducted a systematic review and meta-analysis to assess the clinical severity of viral co-infections as compared to single viral respiratory infections. METHODS: We searched electronic databases and other sources for studies published up to January 28, 2013. We included observational studies on inpatients with respiratory illnesses comparing the clinical severity of viral co-infections to single viral infections as detected by molecular assays. The primary outcome reflecting clinical disease severity was length of hospital stay (LOS). A random-effects model was used to conduct the meta-analyses. RESULTS: Twenty-one studies involving 4,280 patients were included. The overall quality of evidence applying the GRADE approach ranged from moderate for oxygen requirements to low for all other outcomes. No significant differences in length of hospital stay (LOS) (mean difference (MD) −0.20 days, 95% CI −0.94, 0.53, p = 0.59), or mortality (RR 2.44, 95% CI 0.86, 6.91, p = 0.09) were documented in subjects with viral co-infections compared to those with a single viral infection. There was no evidence for differences in effects across age subgroups in post hoc analyses with the exception of the higher mortality in preschool children (RR 9.82, 95% CI 3.09, 31.20, p<0.001) with viral co-infection as compared to other age groups (I(2) for subgroup analysis 64%, p = 0.04). CONCLUSIONS: No differences in clinical disease severity between viral co-infections and single respiratory infections were documented. The suggested increased risk of mortality observed amongst children with viral co-infections requires further investigation.",2014 Jun 16,"['Asner, Sandra A.', 'Science, Michelle E.', 'Tran, Dat', 'Smieja, Marek', 'Merglen, Arnaud', 'Mertz, Dominik']",PLoS One,,,True
181d47c4050ebc63d4831f8dd0df88b785bf4985,PMC,"Antimicrobial, Antiviral and Immunomodulatory Activity Studies of Pelargonium sidoides (EPs(®) 7630) in the Context of Health Promotion",http://dx.doi.org/10.3390/ph4101295,PMC4060126,27721327,CC BY,"Pelargonium species contribute significantly to the health care of a large population in the Southern African region, as part of a long-standing medical system intimately linked to traditional healing practices. Most notably, extracts of the roots of P. sidoides have commonly been applied for the treatment of dysentery and diarrhoea but only occasionally for respiratory complaints. Clinical trials have shown that a modern aqueous-ethanolic formulation of P. sidoides extracts (EPs(®) 7630) is an efficacious treatment for disorders of the respiratory tract, for example bronchitis and sinusitis. It should be noted that EPs(®) 7630 is the most widely investigated extract and therefore is the focus of this review. In order to provide a rationale for its therapeutic activity extracts have been evaluated for antibacterial activity and for their effects on non-specific immune functions. Only moderate direct antibacterial capabilities against a spectrum of bacteria, including Mycobacteria strains, have been noted. In contrast, a large body of in vitro studies has provided convincing evidence for an anti-infective principle associated with activation of the non-specific immune system. Interestingly, significant inhibition of interaction between bacteria and host cells, a key to the pathogenesis of respiratory tract infections, has emerged from recent studies. In addition, antiviral effects have been demonstrated, including inhibition of the replication of respiratory viruses and the enzymes haemagglutinin and neuraminidase. Besides, an increase of cilliary beat frequency of respiratory cells may contribute to the beneficial effects of P. sidoides extracts. This example provides a compelling argument for continuing the exploration of Nature and traditional medical systems as a source of therapeutically useful herbal medicines.",2011 Oct 10,"Kolodziej, Herbert",Pharmaceuticals (Basel),,,True
5c4e986c0995292d3e3839bb20c20b95039ae9d4,PMC,ELR(+) chemokine signaling in host defense and disease in a viral model of central nervous system disease,http://dx.doi.org/10.3389/fncel.2014.00165,PMC4060560,24987333,CC BY,"Intracranial infection of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of susceptible strains of mice results in an acute encephalomyelitis, accompanied by viral replication in glial cells and robust infiltration of virus-specific T cells that contribute to host defense through cytokine secretion and cytolytic activity. Mice surviving the acute stage of disease develop an immune-mediated demyelinating disease, characterized by viral persistence in white matter tracts and a chronic neuroinflammatory response dominated by T cells and macrophages. Chemokines and their corresponding chemokine receptors are dynamically expressed throughout viral infection of the CNS, influencing neuroinflammation by regulating immune cell infltration and glial biology. This review is focused upon the pleiotropic chemokine receptor CXCR2 and its effects upon neutrophils and oligodendrocytes during JHMV infection and a number of other models of CNS inflammation.",2014 Jun 17,"['Hosking, Martin P.', 'Lane, Thomas E.']",Front Cell Neurosci,,,True
9761b5e2c50841879b9ec0fff753ec88ece36744,PMC,"Coronavirus infection, ER stress, apoptosis and innate immunity",http://dx.doi.org/10.3389/fmicb.2014.00296,PMC4060729,24987391,CC BY,"The replication of coronavirus, a family of important animal and human pathogens, is closely associated with the cellular membrane compartments, especially the endoplasmic reticulum (ER). Coronavirus infection of cultured cells was previously shown to cause ER stress and induce the unfolded protein response (UPR), a process that aims to restore the ER homeostasis by global translation shutdown and increasing the ER folding capacity. However, under prolonged ER stress, UPR can also induce apoptotic cell death. Accumulating evidence from recent studies has shown that induction of ER stress and UPR may constitute a major aspect of coronavirus–host interaction. Activation of the three branches of UPR modulates a wide variety of signaling pathways, such as mitogen-activated protein (MAP) kinase activation, autophagy, apoptosis, and innate immune response. ER stress and UPR activation may therefore contribute significantly to the viral replication and pathogenesis during coronavirus infection. In this review, we summarize the current knowledge on coronavirus-induced ER stress and UPR activation, with emphasis on their cross-talking to apoptotic signaling.",2014 Jun 17,"['Fung, To S.', 'Liu, Ding X.']",Front Microbiol,,,True
ba2009991ed471ace18c92633780cd180404c4a9,PMC,Package of NDV-Pseudotyped HIV-Luc Virus and Its Application in the Neutralization Assay for NDV Infection,http://dx.doi.org/10.1371/journal.pone.0099905,PMC4061091,24937158,CC BY,"Newcastle disease virus (NDV) is a member of the Paramyxovirinae subfamily and can infect most species of birds. It has been a great threat for the poultry industry all around the world. In this report, we successfully produced infectious pseudotyped pNL4-3-Luc-R(−)E(−) (HIV-Luc) viruses with the HN and F envelope proteins of NDV. Further investigation revealed the cytoplasmic domains of HN and F, especially HN, plays a significant role in the infection efficiency of these pseudotyped HIV-Luc viruses. Replacement of, or direct fusion to the cytoplasmic domain of the HN protein by that of vesicular stomatitis virus G (VSV-G) could greatly enhance or destroy the infective potential of HN and F-pseudotyped (NDV-pseudotyped) HIV-Luc virus. We further established a novel neutralization assay to evaluate neutralizing antibodies against NDV with the NDV-pseudotyped HIV-Luc viruses. Comparative neutralization data indicate that the results determined by using the NDV-pseudotyped HIV-Luc viruses are as reliable as those by the conventional virus-neutralization assay (VN test) with native NDV. Moreover, the results show that the novel neutralization assay is more sensitive than the VN test.",2014 Jun 17,"['Wang, Bin', 'Wang, Bin', 'Liu, Peixin', 'Li, Tao', 'Si, Wei', 'Xiu, Jinsheng', 'Liu, Henggui']",PLoS One,,,True
ef58c6e2790539f30df14acc260ae2af4b5f3d1f,PMC,Can’t RIDD off viruses,http://dx.doi.org/10.3389/fmicb.2014.00292,PMC4061530,24995003,CC BY,"The mammalian genome has evolved to encode a battery of mechanisms, to mitigate a progression in the life cycle of an invasive viral pathogen. Although apparently disadvantaged by their dependence on the host biosynthetic processes, an immensely faster rate of evolution provides viruses with an edge in this conflict. In this review, I have discussed the potential anti-virus activity of inositol-requiring enzyme 1 (IRE1), a well characterized effector of the cellular homeostatic response to an overloading of the endoplasmic reticulum (ER) protein-folding capacity. IRE1, an ER-membrane-resident ribonuclease (RNase), upon activation catalyses regulated cleavage of select protein-coding and non-coding host RNAs, using an RNase domain which is homologous to that of the known anti-viral effector RNaseL. The latter operates as part of the Oligoadenylate synthetase OAS/RNaseL system of anti-viral defense mechanism. Protein-coding RNA substrates are differentially treated by the IRE1 RNase to either augment, through cytoplasmic splicing of an intron in the Xbp1 transcript, or suppress gene expression. This referred suppression of gene expression is mediated through degradative cleavage of a select cohort of cellular RNA transcripts, initiating the regulated IRE1-dependent decay (RIDD) pathway. The review first discusses the anti-viral mechanism of the OAS/RNaseL system and evasion tactics employed by different viruses. This is followed by a review of the RIDD pathway and its potential effect on the stability of viral RNAs. I conclude with a comparison of the enzymatic activity of the two RNases followed by deliberations on the physiological consequences of their activation.",2014 Jun 18,"Bhattacharyya, Sankar",Front Microbiol,,,True
4055104522be7b53cb86035004c9406b118199f7,PMC,A Compact Immunoassay Platform Based on a Multicapillary Glass Plate,http://dx.doi.org/10.3390/s140509132,PMC4063063,24859022,CC BY,"A highly sensitive, rapid immunoassay performed in the multi-channels of a micro-well array consisting of a multicapillary glass plate (MCP) and a polydimethylsiloxane (PDMS) slide is described. The micro-dimensions and large surface area of the MCP permitted the diffusion distance to be decreased and the reaction efficiency to be increased. To confirm the concept of the method, human immunoglobulin A (h-IgA) was measured using both the proposed immunoassay system and the traditional 96-well plate method. The proposed method resulted in a 1/5-fold decrease of immunoassay time, and a 1/56-fold cut in reagent consumption with a 0.05 ng/mL of limit of detection (LOD) for IgA. The method was also applied to saliva samples obtained from healthy volunteers. The results correlated well to those obtained by the 96-well plate method. The method has the potential for use in disease diagnostic or on-site immunoassays.",2014 May 23,"['Xue, Shuhua', 'Zeng, Hulie', 'Yang, Jianmin', 'Nakajima, Hizuru', 'Uchiyama, Katsumi']",Sensors (Basel),,,True
d8a900446a0ac1e4d0096ab06f805c253a75523c,PMC,"Viral Etiologies of Hospitalized Acute Lower Respiratory Infection Patients in China, 2009-2013",http://dx.doi.org/10.1371/journal.pone.0099419,PMC4063718,24945280,CC BY,"BACKGROUND: Acute lower respiratory infections (ALRIs) are an important cause of acute illnesses and mortality worldwide and in China. However, a large-scale study on the prevalence of viral infections across multiple provinces and seasons has not been previously reported from China. Here, we aimed to identify the viral etiologies associated with ALRIs from 22 Chinese provinces. METHODS AND FINDINGS: Active surveillance for hospitalized ALRI patients in 108 sentinel hospitals in 24 provinces of China was conducted from January 2009-September 2013. We enrolled hospitalized all-age patients with ALRI, and collected respiratory specimens, blood or serum collected for diagnostic testing for respiratory syncytial virus (RSV), human influenza virus, adenoviruses (ADV), human parainfluenza virus (PIV), human metapneumovirus (hMPV), human coronavirus (hCoV) and human bocavirus (hBoV). We included 28,369 ALRI patients from 81 (of the 108) sentinel hospitals in 22 (of the 24) provinces, and 10,387 (36.6%) were positive for at least one etiology. The most frequently detected virus was RSV (9.9%), followed by influenza (6.6%), PIV (4.8%), ADV (3.4%), hBoV (1.9), hMPV (1.5%) and hCoV (1.4%). Co-detections were found in 7.2% of patients. RSV was the most common etiology (17.0%) in young children aged <2 years. Influenza viruses were the main cause of the ALRIs in adults and elderly. PIV, hBoV, hMPV and ADV infections were more frequent in children, while hCoV infection was distributed evenly in all-age. There were clear seasonal peaks for RSV, influenza, PIV, hBoV and hMPV infections. CONCLUSIONS: Our findings could serve as robust evidence for public health authorities in drawing up further plans to prevent and control ALRIs associated with viral pathogens. RSV is common in young children and prevention measures could have large public health impact. Influenza was most common in adults and influenza vaccination should be implemented on a wider scale in China.",2014 Jun 19,"['Feng, Luzhao', 'Li, Zhongjie', 'Zhao, Shiwen', 'Nair, Harish', 'Lai, Shengjie', 'Xu, Wenbo', 'Li, Mengfeng', 'Wu, Jianguo', 'Ren, Lili', 'Liu, Wei', 'Yuan, Zhenghong', 'Chen, Yu', 'Wang, Xinhua', 'Zhao, Zhuo', 'Zhang, Honglong', 'Li, Fu', 'Ye, Xianfei', 'Li, Sa', 'Feikin, Daniel', 'Yu, Hongjie', 'Yang, Weizhong']",PLoS One,,,True
359aef6ff466266be0ea21eb665fb887cec16713,PMC,Associations between Single Nucleotide Polymorphisms in Cellular Viral Receptors and Attachment Factor-Related Genes and Humoral Immunity to Rubella Vaccination,http://dx.doi.org/10.1371/journal.pone.0099997,PMC4063777,24945853,CC BY,"BACKGROUND: Viral attachment and cell entry host factors are important for viral replication, pathogenesis, and the generation and sustenance of immune responses after infection and/or vaccination, and are plausible genetic regulators of vaccine-induced immunity. METHODS: Using a tag-SNP approach in candidate gene study, we assessed the role of selected cell surface receptor genes, attachment factor-related genes, along with other immune genes in the genetic control of immune response variations after live rubella vaccination in two independent study cohorts. RESULTS: Our analysis revealed evidence for multiple associations between genetic variants in the PVR, PVRL2, CD209/DC-SIGN, RARB, MOG, IL6 and other immune function-related genes and rubella-specific neutralizing antibodies after vaccination (meta p-value <0.05). CONCLUSION: Our results indicate that multiple SNPs from genes involved in cell adhesion, viral attachment, and viral entry, as well as others in genes involved in signaling and/or immune response regulation, play a role in modulating humoral immune responses following live rubella vaccination.",2014 Jun 19,"['Haralambieva, Iana H.', 'Lambert, Nathaniel D.', 'Ovsyannikova, Inna G.', 'Kennedy, Richard B.', 'Larrabee, Beth R.', 'Pankratz, V. Shane', 'Poland, Gregory A.']",PLoS One,,,True
d647c6b65ee08b38ecbd2bb85de064df41f7cf0f,PMC,Public perceptions of non-pharmaceutical interventions for reducing transmission of respiratory infection: systematic review and synthesis of qualitative studies,http://dx.doi.org/10.1186/1471-2458-14-589,PMC4063987,24920395,CC BY,"BACKGROUND: Non-pharmaceutical public health interventions may provide simple, low-cost, effective ways of minimising the transmission and impact of acute respiratory infections in pandemic and non-pandemic contexts. Understanding what influences the uptake of non-pharmaceutical interventions such as hand and respiratory hygiene, mask wearing and social distancing could help to inform the development of effective public health advice messages. The aim of this synthesis was to explore public perceptions of non-pharmaceutical interventions that aim to reduce the transmission of acute respiratory infections. METHODS: Five online databases (MEDLINE, PsycINFO, CINAHL, EMBASE and Web of Science) were systematically searched. Reference lists of articles were also examined. We selected papers that used a qualitative research design to explore perceptions and beliefs about non-pharmaceutical interventions to reduce transmission of acute respiratory infections. We excluded papers that only explored how health professionals or children viewed non-pharmaceutical respiratory infection control. Three authors performed data extraction and assessment of study quality. Thematic analysis and components of meta-ethnography were adopted to synthesise findings. RESULTS: Seventeen articles from 16 studies in 9 countries were identified and reviewed. Seven key themes were identified: perceived benefits of non-pharmaceutical interventions, perceived disadvantages of non-pharmaceutical interventions, personal and cultural beliefs about infection transmission, diagnostic uncertainty in emerging respiratory infections, perceived vulnerability to infection, anxiety about emerging respiratory infections and communications about emerging respiratory infections. The synthesis showed that some aspects of non-pharmaceutical respiratory infection control (particularly hand and respiratory hygiene) were viewed as familiar and socially responsible actions to take. There was ambivalence about adopting isolation and personal distancing behaviours in some contexts due to their perceived adverse impact and potential to attract social stigma. Common perceived barriers included beliefs about infection transmission, personal vulnerability to respiratory infection and concerns about self-diagnosis in emerging respiratory infections. CONCLUSIONS: People actively evaluate non-pharmaceutical interventions in terms of their perceived necessity, efficacy, acceptability, and feasibility. To enhance uptake, it will be necessary to address key barriers, such as beliefs about infection transmission, rejection of personal risk of infection and concern about the potential costs and stigma associated with some interventions.",2014 Jun 11,"['Teasdale, Emma', 'Santer, Miriam', 'Geraghty, Adam W A', 'Little, Paul', 'Yardley, Lucy']",BMC Public Health,,,True
c6024a8ca787b4af96d36292b86479031416a0b6,PMC,A fast and robust iterative algorithm for prediction of RNA pseudoknotted secondary structures,http://dx.doi.org/10.1186/1471-2105-15-147,PMC4064103,24884954,CC BY,"BACKGROUND: Improving accuracy and efficiency of computational methods that predict pseudoknotted RNA secondary structures is an ongoing challenge. Existing methods based on free energy minimization tend to be very slow and are limited in the types of pseudoknots that they can predict. Incorporating known structural information can improve prediction accuracy; however, there are not many methods for prediction of pseudoknotted structures that can incorporate structural information as input. There is even less understanding of the relative robustness of these methods with respect to partial information. RESULTS: We present a new method, Iterative HFold, for pseudoknotted RNA secondary structure prediction. Iterative HFold takes as input a pseudoknot-free structure, and produces a possibly pseudoknotted structure whose energy is at least as low as that of any (density-2) pseudoknotted structure containing the input structure. Iterative HFold leverages strengths of earlier methods, namely the fast running time of HFold, a method that is based on the hierarchical folding hypothesis, and the energy parameters of HotKnots V2.0. Our experimental evaluation on a large data set shows that Iterative HFold is robust with respect to partial information, with average accuracy on pseudoknotted structures steadily increasing from roughly 54% to 79% as the user provides up to 40% of the input structure. Iterative HFold is much faster than HotKnots V2.0, while having comparable accuracy. Iterative HFold also has significantly better accuracy than IPknot on our HK-PK and IP-pk168 data sets. CONCLUSIONS: Iterative HFold is a robust method for prediction of pseudoknotted RNA secondary structures, whose accuracy with more than 5% information about true pseudoknot-free structures is better than that of IPknot, and with about 35% information about true pseudoknot-free structures compares well with that of HotKnots V2.0 while being significantly faster. Iterative HFold and all data used in this work are freely available at http://www.cs.ubc.ca/~hjabbari/software.php.",2014 May 18,"['Jabbari, Hosna', 'Condon, Anne']",BMC Bioinformatics,,,True
a04f2512a74dc49c895acb697ee84d9a22101dc1,PMC,A fast and robust iterative algorithm for prediction of RNA pseudoknotted secondary structures,http://dx.doi.org/10.1186/1471-2105-15-147,PMC4064103,24884954,CC BY,"BACKGROUND: Improving accuracy and efficiency of computational methods that predict pseudoknotted RNA secondary structures is an ongoing challenge. Existing methods based on free energy minimization tend to be very slow and are limited in the types of pseudoknots that they can predict. Incorporating known structural information can improve prediction accuracy; however, there are not many methods for prediction of pseudoknotted structures that can incorporate structural information as input. There is even less understanding of the relative robustness of these methods with respect to partial information. RESULTS: We present a new method, Iterative HFold, for pseudoknotted RNA secondary structure prediction. Iterative HFold takes as input a pseudoknot-free structure, and produces a possibly pseudoknotted structure whose energy is at least as low as that of any (density-2) pseudoknotted structure containing the input structure. Iterative HFold leverages strengths of earlier methods, namely the fast running time of HFold, a method that is based on the hierarchical folding hypothesis, and the energy parameters of HotKnots V2.0. Our experimental evaluation on a large data set shows that Iterative HFold is robust with respect to partial information, with average accuracy on pseudoknotted structures steadily increasing from roughly 54% to 79% as the user provides up to 40% of the input structure. Iterative HFold is much faster than HotKnots V2.0, while having comparable accuracy. Iterative HFold also has significantly better accuracy than IPknot on our HK-PK and IP-pk168 data sets. CONCLUSIONS: Iterative HFold is a robust method for prediction of pseudoknotted RNA secondary structures, whose accuracy with more than 5% information about true pseudoknot-free structures is better than that of IPknot, and with about 35% information about true pseudoknot-free structures compares well with that of HotKnots V2.0 while being significantly faster. Iterative HFold and all data used in this work are freely available at http://www.cs.ubc.ca/~hjabbari/software.php.",2014 May 18,"['Jabbari, Hosna', 'Condon, Anne']",BMC Bioinformatics,,,False
a686bbe47aebbb5fd7c29a4f3da4f83271ff9c3e,PMC,A fast and robust iterative algorithm for prediction of RNA pseudoknotted secondary structures,http://dx.doi.org/10.1186/1471-2105-15-147,PMC4064103,24884954,CC BY,"BACKGROUND: Improving accuracy and efficiency of computational methods that predict pseudoknotted RNA secondary structures is an ongoing challenge. Existing methods based on free energy minimization tend to be very slow and are limited in the types of pseudoknots that they can predict. Incorporating known structural information can improve prediction accuracy; however, there are not many methods for prediction of pseudoknotted structures that can incorporate structural information as input. There is even less understanding of the relative robustness of these methods with respect to partial information. RESULTS: We present a new method, Iterative HFold, for pseudoknotted RNA secondary structure prediction. Iterative HFold takes as input a pseudoknot-free structure, and produces a possibly pseudoknotted structure whose energy is at least as low as that of any (density-2) pseudoknotted structure containing the input structure. Iterative HFold leverages strengths of earlier methods, namely the fast running time of HFold, a method that is based on the hierarchical folding hypothesis, and the energy parameters of HotKnots V2.0. Our experimental evaluation on a large data set shows that Iterative HFold is robust with respect to partial information, with average accuracy on pseudoknotted structures steadily increasing from roughly 54% to 79% as the user provides up to 40% of the input structure. Iterative HFold is much faster than HotKnots V2.0, while having comparable accuracy. Iterative HFold also has significantly better accuracy than IPknot on our HK-PK and IP-pk168 data sets. CONCLUSIONS: Iterative HFold is a robust method for prediction of pseudoknotted RNA secondary structures, whose accuracy with more than 5% information about true pseudoknot-free structures is better than that of IPknot, and with about 35% information about true pseudoknot-free structures compares well with that of HotKnots V2.0 while being significantly faster. Iterative HFold and all data used in this work are freely available at http://www.cs.ubc.ca/~hjabbari/software.php.",2014 May 18,"['Jabbari, Hosna', 'Condon, Anne']",BMC Bioinformatics,,,False
88122d733a2f4dcfa0aed0803994aa7402c1c369,PMC,A fast and robust iterative algorithm for prediction of RNA pseudoknotted secondary structures,http://dx.doi.org/10.1186/1471-2105-15-147,PMC4064103,24884954,CC BY,"BACKGROUND: Improving accuracy and efficiency of computational methods that predict pseudoknotted RNA secondary structures is an ongoing challenge. Existing methods based on free energy minimization tend to be very slow and are limited in the types of pseudoknots that they can predict. Incorporating known structural information can improve prediction accuracy; however, there are not many methods for prediction of pseudoknotted structures that can incorporate structural information as input. There is even less understanding of the relative robustness of these methods with respect to partial information. RESULTS: We present a new method, Iterative HFold, for pseudoknotted RNA secondary structure prediction. Iterative HFold takes as input a pseudoknot-free structure, and produces a possibly pseudoknotted structure whose energy is at least as low as that of any (density-2) pseudoknotted structure containing the input structure. Iterative HFold leverages strengths of earlier methods, namely the fast running time of HFold, a method that is based on the hierarchical folding hypothesis, and the energy parameters of HotKnots V2.0. Our experimental evaluation on a large data set shows that Iterative HFold is robust with respect to partial information, with average accuracy on pseudoknotted structures steadily increasing from roughly 54% to 79% as the user provides up to 40% of the input structure. Iterative HFold is much faster than HotKnots V2.0, while having comparable accuracy. Iterative HFold also has significantly better accuracy than IPknot on our HK-PK and IP-pk168 data sets. CONCLUSIONS: Iterative HFold is a robust method for prediction of pseudoknotted RNA secondary structures, whose accuracy with more than 5% information about true pseudoknot-free structures is better than that of IPknot, and with about 35% information about true pseudoknot-free structures compares well with that of HotKnots V2.0 while being significantly faster. Iterative HFold and all data used in this work are freely available at http://www.cs.ubc.ca/~hjabbari/software.php.",2014 May 18,"['Jabbari, Hosna', 'Condon, Anne']",BMC Bioinformatics,,,False
68eb9f309e762e8265822b96e7a6c6fa5814e959,PMC,A fast and robust iterative algorithm for prediction of RNA pseudoknotted secondary structures,http://dx.doi.org/10.1186/1471-2105-15-147,PMC4064103,24884954,CC BY,"BACKGROUND: Improving accuracy and efficiency of computational methods that predict pseudoknotted RNA secondary structures is an ongoing challenge. Existing methods based on free energy minimization tend to be very slow and are limited in the types of pseudoknots that they can predict. Incorporating known structural information can improve prediction accuracy; however, there are not many methods for prediction of pseudoknotted structures that can incorporate structural information as input. There is even less understanding of the relative robustness of these methods with respect to partial information. RESULTS: We present a new method, Iterative HFold, for pseudoknotted RNA secondary structure prediction. Iterative HFold takes as input a pseudoknot-free structure, and produces a possibly pseudoknotted structure whose energy is at least as low as that of any (density-2) pseudoknotted structure containing the input structure. Iterative HFold leverages strengths of earlier methods, namely the fast running time of HFold, a method that is based on the hierarchical folding hypothesis, and the energy parameters of HotKnots V2.0. Our experimental evaluation on a large data set shows that Iterative HFold is robust with respect to partial information, with average accuracy on pseudoknotted structures steadily increasing from roughly 54% to 79% as the user provides up to 40% of the input structure. Iterative HFold is much faster than HotKnots V2.0, while having comparable accuracy. Iterative HFold also has significantly better accuracy than IPknot on our HK-PK and IP-pk168 data sets. CONCLUSIONS: Iterative HFold is a robust method for prediction of pseudoknotted RNA secondary structures, whose accuracy with more than 5% information about true pseudoknot-free structures is better than that of IPknot, and with about 35% information about true pseudoknot-free structures compares well with that of HotKnots V2.0 while being significantly faster. Iterative HFold and all data used in this work are freely available at http://www.cs.ubc.ca/~hjabbari/software.php.",2014 May 18,"['Jabbari, Hosna', 'Condon, Anne']",BMC Bioinformatics,,,False
9ca17c3afd9591b30a57bb00f6af2957f37c1b8a,PMC,"Molecular epidemiology of Porcine torovirus (PToV) in Sichuan Province, China: 2011–2013",http://dx.doi.org/10.1186/1743-422X-11-106,PMC4064267,24903213,CC BY,"BACKGROUND: Porcine torovirus (PToV) is a member of the genus Torovirus which is responsible for gastrointestinal disease in both human beings and animals with particular prevalence in youth. Torovirus infections are generally asymptomatic, however, their presence may worsen disease consequences in concurrent infections with other enteric pathogens. METHODS: A total of 872 diarrheic fecal samples from pigs of different ages were collected from 12 districts of Sichuan Province in the southwest of China. RT-PCR was done with PToV S gene specific primers to detect the presence of PToV positive samples. M gene specific primers were used with the PToV positive samples and the genes were sequenced. A phylogenetic tree was constructed based on the M gene nucleotide sequences from the 19 selected novel Sichuan strains and 21 PToV and BToV M gene sequences from GenBank. RESULTS: A total of 331 (37.96%, 331/872) samples were found to be positive for PToV and the highest prevalence was observed in piglets aged from 1 to 3 weeks old. Through phylogenetic inference the 40 PToV M gene containing sequences were placed into two genotypes (I & II). The 19 novel Sichuan strains of genotype I showed strong correlations to two Korean gene sequences (GU-07-56-11 and GU-07-56-22). Amino-acid sequence analysis of the 40 PToV M gene strains revealed that the M gene protein was highly conserved. CONCLUSIONS: This study uncovered the presence of PToV in Sichuan Province, and demonstrated the need for continuous surveillance PToV of epidemiology.",2014 Jun 5,"['Zhou, Lu', 'Wei, Haoche', 'Zhou, Yuancheng', 'Xu, Zhiwen', 'Zhu, Ling', 'Horne, Jim']",Virol J,,,True
e10af65e4c33f25a580260de1b277ca738dcc886,PMC,"Characterization of the Ectodomain of the Envelope Protein of Dengue Virus Type 4: Expression, Membrane Association, Secretion and Particle Formation in the Absence of Precursor Membrane Protein",http://dx.doi.org/10.1371/journal.pone.0100641,PMC4065094,24950216,CC BY,"BACKGROUND: The envelope (E) of dengue virus (DENV) is the major target of neutralizing antibodies and vaccine development. After biosynthesis E protein forms a heterodimer with precursor membrane (prM) protein. Recent reports of infection enhancement by anti-prM monoclonal antibodies (mAbs) suggest anti-prM responses could be potentially harmful. Previously, we studied a series of C-terminal truncation constructs expressing DENV type 4 prM/E or E proteins and found the ectodomain of E protein alone could be recognized by all 12 mAbs tested, suggesting E protein ectodomain as a potential subunit immunogen without inducing anti-prM response. The characteristics of DENV E protein ectodomain in the absence of prM protein remains largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the expression, membrane association, glycosylation pattern, secretion and particle formation of E protein ectodomain of DENV4 in the presence or absence of prM protein. E protein ectodomain associated with membrane in or beyond trans-Golgi and contained primarily complex glycans, whereas full-length E protein associated with ER membrane and contained high mannose glycans. In the absence of prM protein, E protein ectodomain can secrete as well as form particles of approximately 49 nm in diameter, as revealed by sucrose gradient ultracentrifugation with or without detergent and electron microscopy. Mutational analysis revealed that the secretion of E protein ectodomain was affected by N-linked glycosylation and could be restored by treatment with ammonia chloride. CONCLUSIONS/SIGNIFICANCE: Considering the enhancement of DENV infectivity by anti-prM antibodies, our findings provide new insights into the expression and secretion of E protein ectodomain in the absence of prM protein and contribute to future subunit vaccine design.",2014 Jun 20,"['Hsieh, Szu-Chia', 'Tsai, Wen-Yang', 'Nerurkar, Vivek R.', 'Wang, Wei-Kung']",PLoS One,,,True
2738ed5788b2eb1a42164c7ddff227105d5ae617,PMC,Maternal immunity enhances Mycoplasma hyopneumoniae vaccination induced cell-mediated immune responses in piglets,http://dx.doi.org/10.1186/1746-6148-10-124,PMC4065585,24903770,CC BY,"BACKGROUND: Passively acquired maternal derived immunity (MDI) is a double-edged sword. Maternal derived antibody-mediated immunity (AMI) and cell-mediated immunity (CMI) are critical immediate defenses for the neonate; however, MDI may interfere with the induction of active immunity in the neonate, i.e. passive interference. The effect of antigen-specific MDI on vaccine-induced AMI and CMI responses to Mycoplasma hyopneumoniae (M. hyopneumoniae) was assessed in neonatal piglets. To determine whether CMI and AMI responses could be induced in piglets with MDI, piglets with high and low levels of maternal M. hyopneumoniae-specific immunity were vaccinated against M. hyopneumoniae at 7 d of age. Piglet M. hyopneumoniae-specific antibody, lymphoproliferation, and delayed type hypersensitivity (DTH) responses were measured 7 d and 14 d post vaccination. RESULTS: Piglets with M. hyopneumoniae-specific MDI failed to show vaccine-induced AMI responses; there was no rise in M. hyopneumoniae antibody levels following vaccination of piglets in the presence of M. hyopneumoniae-specific MDI. However, piglets with M. hyopneumoniae-specific MDI had primary (antigen-specific lymphoproliferation) and secondary (DTH) M. hyopneumoniae-specific CMI responses following vaccination. CONCLUSIONS: In this study neonatal M. hyopneumoniae-specific CMI was not subject to passive interference by MDI. Further, it appears that both maternal derived and endogenous CMI contribute to M. hyopneumoniae-specific CMI responses in piglets vaccinated in the face of MDI.",2014 Jun 5,"['Bandrick, Meggan', 'Theis, Kara', 'Molitor, Thomas W']",BMC Vet Res,,,True
9adb161f0e769ea8de09f4138cc40f206d586003,PMC,Analysis of tetra- and hepta-nucleotides motifs promoting -1 ribosomal frameshifting in Escherichia coli,http://dx.doi.org/10.1093/nar/gku386,PMC4066793,24875478,CC BY,"Programmed ribosomal -1 frameshifting is a non-standard decoding process occurring when ribosomes encounter a signal embedded in the mRNA of certain eukaryotic and prokaryotic genes. This signal has a mandatory component, the frameshift motif: it is either a Z_ZZN tetramer or a X_XXZ_ZZN heptamer (where ZZZ and XXX are three identical nucleotides) allowing cognate or near-cognate repairing to the -1 frame of the A site or A and P sites tRNAs. Depending on the signal, the frameshifting frequency can vary over a wide range, from less than 1% to more than 50%. The present study combines experimental and bioinformatics approaches to carry out (i) a systematic analysis of the frameshift propensity of all possible motifs (16 Z_ZZN tetramers and 64 X_XXZ_ZZN heptamers) in Escherichia coli and (ii) the identification of genes potentially using this mode of expression amongst 36 Enterobacteriaceae genomes. While motif efficiency varies widely, a major distinctive rule of bacterial -1 frameshifting is that the most efficient motifs are those allowing cognate re-pairing of the A site tRNA from ZZN to ZZZ. The outcome of the genomic search is a set of 69 gene clusters, 59 of which constitute new candidates for functional utilization of -1 frameshifting.",2014 Jul 1,"['Sharma, Virag', 'Prère, Marie-Françoise', 'Canal, Isabelle', 'Firth, Andrew E.', 'Atkins, John F.', 'Baranov, Pavel V.', 'Fayet, Olivier']",Nucleic Acids Res,,,True
0369a40d60dd1a4366529493f90c3e5bcea8a0f4,PMC,Analysis of tetra- and hepta-nucleotides motifs promoting -1 ribosomal frameshifting in Escherichia coli,http://dx.doi.org/10.1093/nar/gku386,PMC4066793,24875478,CC BY,"Programmed ribosomal -1 frameshifting is a non-standard decoding process occurring when ribosomes encounter a signal embedded in the mRNA of certain eukaryotic and prokaryotic genes. This signal has a mandatory component, the frameshift motif: it is either a Z_ZZN tetramer or a X_XXZ_ZZN heptamer (where ZZZ and XXX are three identical nucleotides) allowing cognate or near-cognate repairing to the -1 frame of the A site or A and P sites tRNAs. Depending on the signal, the frameshifting frequency can vary over a wide range, from less than 1% to more than 50%. The present study combines experimental and bioinformatics approaches to carry out (i) a systematic analysis of the frameshift propensity of all possible motifs (16 Z_ZZN tetramers and 64 X_XXZ_ZZN heptamers) in Escherichia coli and (ii) the identification of genes potentially using this mode of expression amongst 36 Enterobacteriaceae genomes. While motif efficiency varies widely, a major distinctive rule of bacterial -1 frameshifting is that the most efficient motifs are those allowing cognate re-pairing of the A site tRNA from ZZN to ZZZ. The outcome of the genomic search is a set of 69 gene clusters, 59 of which constitute new candidates for functional utilization of -1 frameshifting.",2014 Jul 1,"['Sharma, Virag', 'Prère, Marie-Françoise', 'Canal, Isabelle', 'Firth, Andrew E.', 'Atkins, John F.', 'Baranov, Pavel V.', 'Fayet, Olivier']",Nucleic Acids Res,,,False
ea3edffefb5fa20412b31e223330af336503afaf,PMC,Accuracy of epidemiological inferences based on publicly available information: retrospective comparative analysis of line lists of human cases infected with influenza A(H7N9) in China,http://dx.doi.org/10.1186/1741-7015-12-88,PMC4066833,24885692,CC BY,"BACKGROUND: Appropriate public health responses to infectious disease threats should be based on best-available evidence, which requires timely reliable data for appropriate analysis. During the early stages of epidemics, analysis of ‘line lists’ with detailed information on laboratory-confirmed cases can provide important insights into the epidemiology of a specific disease. The objective of the present study was to investigate the extent to which reliable epidemiologic inferences could be made from publicly-available epidemiologic data of human infection with influenza A(H7N9) virus. METHODS: We collated and compared six different line lists of laboratory-confirmed human cases of influenza A(H7N9) virus infection in the 2013 outbreak in China, including the official line list constructed by the Chinese Center for Disease Control and Prevention plus five other line lists by HealthMap, Virginia Tech, Bloomberg News, the University of Hong Kong and FluTrackers, based on publicly-available information. We characterized clinical severity and transmissibility of the outbreak, using line lists available at specific dates to estimate epidemiologic parameters, to replicate real-time inferences on the hospitalization fatality risk, and the impact of live poultry market closure. RESULTS: Demographic information was mostly complete (less than 10% missing for all variables) in different line lists, but there were more missing data on dates of hospitalization, discharge and health status (more than 10% missing for each variable). The estimated onset to hospitalization distributions were similar (median ranged from 4.6 to 5.6 days) for all line lists. Hospital fatality risk was consistently around 20% in the early phase of the epidemic for all line lists and approached the final estimate of 35% afterwards for the official line list only. Most of the line lists estimated >90% reduction in incidence rates after live poultry market closures in Shanghai, Nanjing and Hangzhou. CONCLUSIONS: We demonstrated that analysis of publicly-available data on H7N9 permitted reliable assessment of transmissibility and geographical dispersion, while assessment of clinical severity was less straightforward. Our results highlight the potential value in constructing a minimum dataset with standardized format and definition, and regular updates of patient status. Such an approach could be particularly useful for diseases that spread across multiple countries.",2014 May 28,"['Lau, Eric HY', 'Zheng, Jiandong', 'Tsang, Tim K', 'Liao, Qiaohong', 'Lewis, Bryan', 'Brownstein, John S', 'Sanders, Sharon', 'Wong, Jessica Y', 'Mekaru, Sumiko R', 'Rivers, Caitlin', 'Wu, Peng', 'Jiang, Hui', 'Li, Yu', 'Yu, Jianxing', 'Zhang, Qian', 'Chang, Zhaorui', 'Liu, Fengfeng', 'Peng, Zhibin', 'Leung, Gabriel M', 'Feng, Luzhao', 'Cowling, Benjamin J', 'Yu, Hongjie']",BMC Med,,,True
af8d060acff4a631e09af5425cdab023103e9d8a,PMC,Accuracy of epidemiological inferences based on publicly available information: retrospective comparative analysis of line lists of human cases infected with influenza A(H7N9) in China,http://dx.doi.org/10.1186/1741-7015-12-88,PMC4066833,24885692,CC BY,"BACKGROUND: Appropriate public health responses to infectious disease threats should be based on best-available evidence, which requires timely reliable data for appropriate analysis. During the early stages of epidemics, analysis of ‘line lists’ with detailed information on laboratory-confirmed cases can provide important insights into the epidemiology of a specific disease. The objective of the present study was to investigate the extent to which reliable epidemiologic inferences could be made from publicly-available epidemiologic data of human infection with influenza A(H7N9) virus. METHODS: We collated and compared six different line lists of laboratory-confirmed human cases of influenza A(H7N9) virus infection in the 2013 outbreak in China, including the official line list constructed by the Chinese Center for Disease Control and Prevention plus five other line lists by HealthMap, Virginia Tech, Bloomberg News, the University of Hong Kong and FluTrackers, based on publicly-available information. We characterized clinical severity and transmissibility of the outbreak, using line lists available at specific dates to estimate epidemiologic parameters, to replicate real-time inferences on the hospitalization fatality risk, and the impact of live poultry market closure. RESULTS: Demographic information was mostly complete (less than 10% missing for all variables) in different line lists, but there were more missing data on dates of hospitalization, discharge and health status (more than 10% missing for each variable). The estimated onset to hospitalization distributions were similar (median ranged from 4.6 to 5.6 days) for all line lists. Hospital fatality risk was consistently around 20% in the early phase of the epidemic for all line lists and approached the final estimate of 35% afterwards for the official line list only. Most of the line lists estimated >90% reduction in incidence rates after live poultry market closures in Shanghai, Nanjing and Hangzhou. CONCLUSIONS: We demonstrated that analysis of publicly-available data on H7N9 permitted reliable assessment of transmissibility and geographical dispersion, while assessment of clinical severity was less straightforward. Our results highlight the potential value in constructing a minimum dataset with standardized format and definition, and regular updates of patient status. Such an approach could be particularly useful for diseases that spread across multiple countries.",2014 May 28,"['Lau, Eric HY', 'Zheng, Jiandong', 'Tsang, Tim K', 'Liao, Qiaohong', 'Lewis, Bryan', 'Brownstein, John S', 'Sanders, Sharon', 'Wong, Jessica Y', 'Mekaru, Sumiko R', 'Rivers, Caitlin', 'Wu, Peng', 'Jiang, Hui', 'Li, Yu', 'Yu, Jianxing', 'Zhang, Qian', 'Chang, Zhaorui', 'Liu, Fengfeng', 'Peng, Zhibin', 'Leung, Gabriel M', 'Feng, Luzhao', 'Cowling, Benjamin J', 'Yu, Hongjie']",BMC Med,,,False
c12642f0762cb4888b417ce295044080ab9202a6,PMC,Macrophage activation state determines the response to rhinovirus infection in a mouse model of allergic asthma,http://dx.doi.org/10.1186/1465-9921-15-63,PMC4066837,24907978,CC BY,"BACKGROUND: The mechanisms by which viruses cause asthma exacerbations are not precisely known. Previously, we showed that, in ovalbumin (OVA)-sensitized and -challenged mice with allergic airway inflammation, rhinovirus (RV) infection increases type 2 cytokine production from alternatively-activated (M2) airway macrophages, enhancing eosinophilic inflammation and airways hyperresponsiveness. In this paper, we tested the hypothesis that IL-4 signaling determines the state of macrophage activation and pattern of RV-induced exacerbation in mice with allergic airways disease. METHODS: Eight week-old wild type or IL-4 receptor knockout (IL-4R KO) mice were sensitized and challenged with OVA and inoculated with RV1B or sham HeLa cell lysate. RESULTS: In contrast to OVA-treated wild-type mice with both neutrophilic and eosinophilic airway inflammation, OVA-treated IL-4R KO mice showed increased neutrophilic inflammation with few eosinophils in the airways. Like wild-type mice, IL-4R KO mice showed OVA-induced airway hyperreactivity which was further exacerbated by RV. There was a shift in lung cytokines from a type 2-predominant response to a type 1 response, including production of IL-12p40 and TNF-α. IL-17A was also increased. RV infection of OVA-treated IL-4R KO mice further increased neutrophilic inflammation. Bronchoalveolar macrophages showed an M1 polarization pattern and ex vivo RV infection increased macrophage production of TNF-α, IFN-γ and IL-12p40. Finally, lung cells from OVA-treated IL-4R KO mice showed reduced CD206+ CD301+ M2 macrophages, decreased IL-13 and increased TNF-α and IL-17A production by F4/80+, CD11b+ macrophages. CONCLUSIONS: OVA-treated IL-4R KO mice show neutrophilic airway inflammation constituting a model of allergic, type 1 cytokine-driven neutrophilic asthma. In the absence of IL-4/IL-13 signaling, RV infection of OVA-treated mice increased type 1 cytokine and IL-17A production from conventionally-activated macrophages, augmenting neutrophilic rather than eosinophilic inflammation. In mice with allergic airways inflammation, IL-4R signaling determines macrophage activation state and the response to subsequent RV infection.",2014 Jun 7,"['Hong, Jun Young', 'Chung, Yutein', 'Steenrod, Jessica', 'Chen, Qiang', 'Lei, Jing', 'Comstock, Adam T', 'Goldsmith, Adam M', 'Bentley, J Kelley', 'Sajjan, Uma S', 'Hershenson, Marc B']",Respir Res,,,True
9c437ea3972c987ed041833f65535b2d4300e095,PMC,Difference in immune response in vaccinated and unvaccinated Swedish individuals after the 2009 influenza pandemic,http://dx.doi.org/10.1186/1471-2334-14-319,PMC4067073,24916787,CC BY,"BACKGROUND: Previous exposures to flu and subsequent immune responses may impact on 2009/2010 pandemic flu vaccine responses and clinical symptoms upon infection with the 2009 pandemic H1N1 influenza strain. Qualitative and quantitative differences in humoral and cellular immune responses associated with the flu vaccination in 2009/2010 (pandemic H1N1 vaccine) and natural infection have not yet been described in detail. We designed a longitudinal study to examine influenza- (flu-) specific immune responses and the association between pre-existing flu responses, symptoms of influenza-like illness (ILI), impact of pandemic flu infection, and pandemic flu vaccination in a cohort of 2,040 individuals in Sweden in 2009–2010. METHODS: Cellular flu-specific immune responses were assessed by whole-blood antigen stimulation assay, and humoral responses by a single radial hemolysis test. RESULTS: Previous seasonal flu vaccination was associated with significantly lower flu-specific IFN-γ responses (using a whole-blood assay) at study entry. Pandemic flu vaccination induced long-lived T-cell responses (measured by IFN-γ production) to influenza A strains, influenza B strains, and the matrix (M1) antigen. In contrast, individuals with pandemic flu infection (PCR positive) exhibited increased flu-specific T-cell responses shortly after onset of ILI symptoms but the immune response decreased after the flu season (spring 2010). We identified non-pandemic-flu vaccinated participants without ILI symptoms who showed an IFN-γ production profile similar to pandemic-flu infected participants, suggesting exposure without experiencing clinical symptoms. CONCLUSIONS: Strong and long-lived flu-M1 specific immune responses, defined by IFN-γ production, in individuals after vaccination suggest that M1-responses may contribute to protective cellular immune responses. Silent flu infections appeared to be frequent in 2009/2010. The pandemic flu vaccine induced qualitatively and quantitatively different humoral and cellular immune responses as compared to infection with the 2009 H1N1 pandemic H1N1 influenza strain.",2014 Jun 11,"['Magalhaes, Isabelle', 'Eriksson, Mikael', 'Linde, Charlotte', 'Muhammad, Rashid', 'Rane, Lalit', 'Ambati, Aditya', 'Axelsson-Robertson, Rebecca', 'Khalaj, Bahareh', 'Alvarez-Corrales, Nancy', 'Lapini, Giulia', 'Montomoli, Emanuele', 'Linde, Annika', 'Pedersen, Nancy L', 'Maeurer, Markus']",BMC Infect Dis,,,True
1434efe4d841738948735807bd1d1f1e9a36225e,PMC,Difference in immune response in vaccinated and unvaccinated Swedish individuals after the 2009 influenza pandemic,http://dx.doi.org/10.1186/1471-2334-14-319,PMC4067073,24916787,CC BY,"BACKGROUND: Previous exposures to flu and subsequent immune responses may impact on 2009/2010 pandemic flu vaccine responses and clinical symptoms upon infection with the 2009 pandemic H1N1 influenza strain. Qualitative and quantitative differences in humoral and cellular immune responses associated with the flu vaccination in 2009/2010 (pandemic H1N1 vaccine) and natural infection have not yet been described in detail. We designed a longitudinal study to examine influenza- (flu-) specific immune responses and the association between pre-existing flu responses, symptoms of influenza-like illness (ILI), impact of pandemic flu infection, and pandemic flu vaccination in a cohort of 2,040 individuals in Sweden in 2009–2010. METHODS: Cellular flu-specific immune responses were assessed by whole-blood antigen stimulation assay, and humoral responses by a single radial hemolysis test. RESULTS: Previous seasonal flu vaccination was associated with significantly lower flu-specific IFN-γ responses (using a whole-blood assay) at study entry. Pandemic flu vaccination induced long-lived T-cell responses (measured by IFN-γ production) to influenza A strains, influenza B strains, and the matrix (M1) antigen. In contrast, individuals with pandemic flu infection (PCR positive) exhibited increased flu-specific T-cell responses shortly after onset of ILI symptoms but the immune response decreased after the flu season (spring 2010). We identified non-pandemic-flu vaccinated participants without ILI symptoms who showed an IFN-γ production profile similar to pandemic-flu infected participants, suggesting exposure without experiencing clinical symptoms. CONCLUSIONS: Strong and long-lived flu-M1 specific immune responses, defined by IFN-γ production, in individuals after vaccination suggest that M1-responses may contribute to protective cellular immune responses. Silent flu infections appeared to be frequent in 2009/2010. The pandemic flu vaccine induced qualitatively and quantitatively different humoral and cellular immune responses as compared to infection with the 2009 H1N1 pandemic H1N1 influenza strain.",2014 Jun 11,"['Magalhaes, Isabelle', 'Eriksson, Mikael', 'Linde, Charlotte', 'Muhammad, Rashid', 'Rane, Lalit', 'Ambati, Aditya', 'Axelsson-Robertson, Rebecca', 'Khalaj, Bahareh', 'Alvarez-Corrales, Nancy', 'Lapini, Giulia', 'Montomoli, Emanuele', 'Linde, Annika', 'Pedersen, Nancy L', 'Maeurer, Markus']",BMC Infect Dis,,,True
8c2cfca9f2eee4a00231a2a3a2cfe1e60e798672,PMC,Inducing Dose Sparing with Inactivated Polio Virus Formulated in Adjuvant CAF01,http://dx.doi.org/10.1371/journal.pone.0100879,PMC4067388,24956110,CC BY,"The development of new low cost inactivated polio virus based vaccines (IPV) is a high priority, and will be required to eradicate polio. In addition, such a vaccine constitutes the only realistic polio vaccine in the post-eradication era. One way to reduce the cost of a vaccine is to increase immunogenicity by use of adjuvants. The CAF01 adjuvant has previously been shown to be a safe and potent adjuvant with several antigens, and here we show that in mice IPV formulated with CAF01 induced increased systemic protective immunity measured by binding and neutralization antibody titers in serum. CAF01 also influenced the kinetics of both the cellular and humoral response against IPV to produce a faster, as well as a stronger, response, dominated by IgG2a, IgG2b, and IgG2c isotypes as well as IPV specific T cells secreting IFN-γ/IL-2. Finally, as intestinal immunity is also a priority of polio vaccines, we present a vaccine strategy based on simultaneous priming at an intradermal and an intramuscular site that generate intestinal immune responses against polio virus. Taken together, the IPV-CAF01 formulation constitutes a new promising vaccine against polio with the ability to generate strong humoral and cellular immunity against the polio virus.",2014 Jun 23,"['Dietrich, Jes', 'Andreasen, Lars Vibe', 'Andersen, Peter', 'Agger, Else Marie']",PLoS One,,,True
458baa469db78afded4d1acdbc4b7d440a5f0a74,PMC,"Results From the First Six Years of National Sentinel Surveillance for Influenza in Kenya, July 2007–June 2013",http://dx.doi.org/10.1371/journal.pone.0098615,PMC4067481,24955962,CC0,"BACKGROUND: Recent studies have shown that influenza is associated with significant disease burden in many countries in the tropics, but until recently national surveillance for influenza was not conducted in most countries in Africa. METHODS: In 2007, the Kenyan Ministry of Health with technical support from the CDC-Kenya established a national sentinel surveillance system for influenza. At 11 hospitals, for every hospitalized patient with severe acute respiratory illness (SARI), and for the first three outpatients with influenza-like illness (ILI) per day, we collected both nasopharyngeal and oropharyngeal swabs. Beginning in 2008, we conducted in-hospital follow-up for SARI patients to determine outcome. Specimens were tested by real time RT-PCR for influenza A and B. Influenza A-positive specimens were subtyped for H1, H3, H5, and (beginning in May 2009) A(H1N1)pdm09. RESULTS: From July 1, 2007 through June 30, 2013, we collected specimens from 24,762 SARI and 14,013 ILI patients. For SARI and ILI case-patients, the median ages were 12 months and 16 months, respectively, and 44% and 47% were female. In all, 2,378 (9.6%) SARI cases and 2,041 (14.6%) ILI cases were positive for influenza viruses. Most influenza-associated SARI cases (58.6%) were in children <2 years old. Of all influenza-positive specimens, 78% were influenza A, 21% were influenza B, and 1% were influenza A/B coinfections. Influenza circulated in every month. In four of the six years influenza activity peaked during July–November. Of 9,419 SARI patients, 2.7% died; the median length of hospitalization was 4 days. CONCLUSIONS: During six years of surveillance in Kenya, influenza was associated with nearly 10 percent of hospitalized SARI cases and one-sixth of outpatient ILI cases. Most influenza-associated SARI and ILI cases were in children <2 years old; interventions to reduce the burden of influenza, such as vaccine, could consider young children as a priority group.",2014 Jun 23,"['Katz, Mark A.', 'Muthoka, Philip', 'Emukule, Gideon O.', 'Kalani, Rosalia', 'Njuguna, Henry', 'Waiboci, Lilian W.', 'Ahmed, Jamal A.', 'Bigogo, Godfrey', 'Feikin, Daniel R.', 'Njenga, Moses K.', 'Breiman, Robert F.', 'Mott, Joshua A.']",PLoS One,,,True
b7f529b58714037f09a19f78d9a06d68f1f15dd9,PMC,From gene to protein—experimental and clinical studies of ACE2 in blood pressure control and arterial hypertension,http://dx.doi.org/10.3389/fphys.2014.00227,PMC4067757,25009501,CC BY,"Hypertension is a major risk factor for stroke, coronary events, heart and renal failure, and the renin-angiotensin system (RAS) plays a major role in its pathogenesis. Within the RAS, angiotensin converting enzyme (ACE) converts angiotensin (Ang) I into the vasoconstrictor Ang II. An “alternate” arm of the RAS now exists in which ACE2 counterbalances the effects of the classic RAS through degradation of Ang II, and generation of the vasodilator Ang 1-7. ACE2 is highly expressed in the heart, blood vessels, and kidney. The catalytically active ectodomain of ACE2 undergoes shedding, resulting in ACE2 in the circulation. The ACE2 gene maps to a quantitative trait locus on the X chromosome in three strains of genetically hypertensive rats, suggesting that ACE2 may be a candidate gene for hypertension. It is hypothesized that disruption of tissue ACE/ACE2 balance results in changes in blood pressure, with increased ACE2 expression protecting against increased blood pressure, and ACE2 deficiency contributing to hypertension. Experimental hypertension studies have measured ACE2 in either the heart or kidney and/or plasma, and have reported that deletion or inhibition of ACE2 leads to hypertension, whilst enhancing ACE2 protects against the development of hypertension, hence increasing ACE2 may be a therapeutic option for the management of high blood pressure in man. There have been relatively few studies of ACE2, either at the gene or the circulating level in patients with hypertension. Plasma ACE2 activity is low in healthy subjects, but elevated in patients with cardiovascular risk factors or cardiovascular disease. Genetic studies have investigated ACE2 gene polymorphisms with either hypertension or blood pressure, and have produced largely inconsistent findings. This review discusses the evidence regarding ACE2 in experimental hypertension models and the association between circulating ACE2 activity and ACE2 polymorphisms with blood pressure and arterial hypertension in man.",2014 Jun 24,"['Patel, Sheila K.', 'Velkoska, Elena', 'Freeman, Melanie', 'Wai, Bryan', 'Lancefield, Terase F.', 'Burrell, Louise M.']",Front Physiol,,,True
df5401bebedec1ea63a7afebb3b4166f775fbd82,PMC,No Evidence of Viral Transmission following Long-Term Implantation of Agarose Encapsulated Porcine Islets in Diabetic Dogs,http://dx.doi.org/10.1155/2014/727483,PMC4068064,24995342,CC BY,"We have previously described the use of a double coated agarose-agarose porcine islet macrobead for the treatment of type I diabetes mellitus. In the current study, the long-term viral safety of macrobead implantation into pancreatectomized diabetic dogs treated with pravastatin (n = 3) was assessed while 2 dogs served as nonimplanted controls. A more gradual return to preimplant insulin requirements occurred after a 2nd implant procedure (days 148, 189, and >652) when compared to a first macrobead implantation (days 9, 21, and 21) in all macrobead implanted animals. In all three implanted dogs, porcine C-peptide was detected in the blood for at least 10 days following the first implant and for at least 26 days following the second implant. C-peptide was also present in the peritoneal fluid of all three implanted dogs at 6 months after 2nd implant and in 2 of 3 dogs at necropsy. Prescreening results of islet macrobeads and culture media prior to transplantation were negative for 13 viruses. No evidence of PERV or other viral transmission was found throughout the study. This study demonstrates that the long-term (2.4 years) implantation of agarose-agarose encapsulated porcine islets is a safe procedure in a large animal model of type I diabetes mellitus.",2014 Jun 5,"['Gazda, Lawrence S.', 'Vinerean, Horatiu V.', 'Laramore, Melissa A.', 'Hall, Richard D.', 'Carraway, Joseph W.', 'Smith, Barry H.']",J Diabetes Res,,,True
153bc127b399f445ca2ec0e0709379efaada43bc,PMC,Unanswered questions about the Middle East respiratory syndrome coronavirus (MERS-CoV),http://dx.doi.org/10.1186/1756-0500-7-358,PMC4068970,24920393,CC BY,"BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) represents a current threat to the Arabian Peninsula, and potential pandemic disease. As of June 3, 2014, MERS CoV has reportedly infected 688 people and killed 282. We briefly summarize the state of the outbreak, and highlight unanswered questions and various explanations for the observed epidemiology. FINDINGS: The continuing but infrequent cases of MERS-CoV reported over the past two years have been puzzling and difficult to explain. The epidemiology of MERS-CoV, with many sporadic cases and a few hospital outbreaks, yet no sustained epidemic, suggests a low reproductive number. Furthermore, a clear source of infection to humans remains unknown. Also puzzling is the fact that MERS-CoV has been present in Saudi Arabia over several mass gatherings, including the 2012 and 2013 Hajj and Umrah pilgrimages, which predispose to epidemics, without an epidemic arising. CONCLUSIONS: The observed epidemiology of MERS-CoV is quite distinct and does not clearly fit either a sporadic or epidemic pattern. Possible explanations of the unusual features of the epidemiology of MERS-CoV include sporadic ongoing infections from a non-human source; human to human transmission with a large proportion of undetected cases; or a combination of both. The virus has been identified in camels; however the mode of transmission of the virus to humans remains unknown, and many cases have no history of animal contact. In order to gain a better understanding of the epidemiology of MERS CoV, further investigation is warranted.",2014 Jun 11,"['Gardner, Lauren M', 'MacIntyre, C Raina']",BMC Res Notes,,,True
8eefe017d2a4fedeac3243fb76f3b417b16023f2,PMC,Bat Distribution Size or Shape as Determinant of Viral Richness in African Bats,http://dx.doi.org/10.1371/journal.pone.0100172,PMC4069033,24959855,CC BY,"The rising incidence of emerging infectious diseases (EID) is mostly linked to biodiversity loss, changes in habitat use and increasing habitat fragmentation. Bats are linked to a growing number of EID but few studies have explored the factors of viral richness in bats. These may have implications for role of bats as potential reservoirs. We investigated the determinants of viral richness in 15 species of African bats (8 Pteropodidae and 7 microchiroptera) in Central and West Africa for which we provide new information on virus infection and bat phylogeny. We performed the first comparative analysis testing the correlation of the fragmented geographical distribution (defined as the perimeter to area ratio) with viral richness in bats. Because of their potential effect, sampling effort, host body weight, ecological and behavioural traits such as roosting behaviour, migration and geographical range, were included into the analysis as variables. The results showed that the geographical distribution size, shape and host body weight have significant effects on viral richness in bats. Viral richness was higher in large-bodied bats which had larger and more fragmented distribution areas. Accumulation of viruses may be related to the historical expansion and contraction of bat species distribution range, with potentially strong effects of distribution edges on virus transmission. Two potential explanations may explain these results. A positive distribution edge effect on the abundance or distribution of some bat species could have facilitated host switches. Alternatively, parasitism could play a direct role in shaping the distribution range of hosts through host local extinction by virulent parasites. This study highlights the importance of considering the fragmentation of bat species geographical distribution in order to understand their role in the circulation of viruses in Africa.",2014 Jun 24,"['Maganga, Gaël D.', 'Bourgarel, Mathieu', 'Vallo, Peter', 'Dallo, Thierno D.', 'Ngoagouni, Carine', 'Drexler, Jan Felix', 'Drosten, Christian', 'Nakouné, Emmanuel R.', 'Leroy, Eric M.', 'Morand, Serge']",PLoS One,,,True
04f4cff6c1a32e0edb50bdb8daf00f82708a5142,PMC,Plasmodium vivax Antigen Discovery Based on Alpha-Helical Coiled Coil Protein Motif,http://dx.doi.org/10.1371/journal.pone.0100440,PMC4069070,24959747,CC BY,"Protein α-helical coiled coil structures that elicit antibody responses, which block critical functions of medically important microorganisms, represent a means for vaccine development. By using bioinformatics algorithms, a total of 50 antigens with α-helical coiled coil motifs orthologous to Plasmodium falciparum were identified in the P. vivax genome. The peptides identified in silico were chemically synthesized; circular dichroism studies indicated partial or high α-helical content. Antigenicity was evaluated using human sera samples from malaria-endemic areas of Colombia and Papua New Guinea. Eight of these fragments were selected and used to assess immunogenicity in BALB/c mice. ELISA assays indicated strong reactivity of serum samples from individuals residing in malaria-endemic regions and sera of immunized mice, with the α-helical coiled coil structures. In addition, ex vivo production of IFN-γ by murine mononuclear cells confirmed the immunogenicity of these structures and the presence of T-cell epitopes in the peptide sequences. Moreover, sera of mice immunized with four of the eight antigens recognized native proteins on blood-stage P. vivax parasites, and antigenic cross-reactivity with three of the peptides was observed when reacted with both the P. falciparum orthologous fragments and whole parasites. Results here point to the α-helical coiled coil peptides as possible P. vivax malaria vaccine candidates as were observed for P. falciparum. Fragments selected here warrant further study in humans and non-human primate models to assess their protective efficacy as single components or assembled as hybrid linear epitopes.",2014 Jun 24,"['Céspedes, Nora', 'Habel, Catherine', 'Lopez-Perez, Mary', 'Castellanos, Angélica', 'Kajava, Andrey V.', 'Servis, Catherine', 'Felger, Ingrid', 'Moret, Remy', 'Arévalo-Herrera, Myriam', 'Corradin, Giampietro', 'Herrera, Sócrates']",PLoS One,,,True
20308c2a1349e993e82115a8dc869c011298dd06,PMC,Epidemiology and Viral Etiology of the Influenza-Like Illness in Corsica during the 2012–2013 Winter: An Analysis of Several Sentinel Surveillance Systems,http://dx.doi.org/10.1371/journal.pone.0100388,PMC4069071,24959929,CC BY,"Influenza-like illness (ILI) surveillance is important to identify circulating and emerging/reemerging strains and unusual epidemiological trends. The present study aimed to give an accurate picture of the 2012–2013 ILI outbreak in Corsica by combining data from several surveillance systems: general practice, emergency general practice, hospital emergency units, intensive care units, and nursing homes. Twenty-eight respiratory viruses were retrospectively investigated from patients in general practice with ILI. Sequence analysis of the genetic changes in the hemagglutinin gene of influenza viruses (A(H1N1)pdm2009, A(H3N2) and B) was performed. The trends in ILI/influenza consultation rates and the relative illness ratios (RIRs) of having an ILI consultation were estimated by age group for the different surveillance systems analyzed. Of the 182 ILI patients enrolled by general practitioners, 57.7% tested positive for influenza viruses. Phylogenetic analyses suggested a genetic drift for influenza B and A(H3N2) viruses. The ILI/influenza surveillance systems showed similar trends and were well correlated. In accordance with virological data, the RIRs of having an ILI consultation were highest among the young (<15 years old) and decreased with age. No clusters of acute respiratory illness were declared by the sentinel nursing homes. This study is noteworthy in that it is the first extensive description of the 2012–2013 ILI outbreak in Corsica as monitored through several surveillance systems. To improve ILI surveillance in Corsica, a consortium that links together the complementary regional surveillance ILI systems described here is being implemented.",2014 Jun 24,"['Minodier, Laëtitia', 'Arena, Christophe', 'Heuze, Guillaume', 'Ruello, Marc', 'Amoros, Jean Pierre', 'Souty, Cécile', 'Varesi, Laurent', 'Falchi, Alessandra']",PLoS One,,,True
fc5cc0fedf50af659b515f25de57a6c7d841d342,PMC,"Yu Ping Feng San, an Ancient Chinese Herbal Decoction, Regulates the Expression of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 and the Activity of Intestinal Alkaline Phosphatase in Cultures",http://dx.doi.org/10.1371/journal.pone.0100382,PMC4072625,24967898,CC BY,"Yu Ping Feng San (YPFS), a Chinese herbal decoction comprising Astragali Radix (AR; Huangqi), Atractylodis Macrocephalae Rhizoma (AMR; Baizhu), and Saposhnikoviae Radix (SR; Fangfeng), has been used clinically to treat inflammatory bowel diseases (IBD). Previously, we demonstrated a dual role of YPFS in regulating cytokine release in cultured macrophages. In this study, we elucidated the anti-inflammatory effect of YPFS that is mediated through modulating the expression of three key enzymes involved in IBD: inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and intestinal alkaline phosphatase (IALP). In a lipopolysaccharide (LPS)-induced chronic-inflammation model of cultured murine macrophages, YPFS treatment suppressed the activation of iNOS and COX-2 expression in a dose-dependent manner. Conversely, application of YPFS in cultured small intestinal enterocytes markedly induced the expression of IALP in a time-dependent manner, which might strengthen the intestinal detoxification system. A duality of YPFS in modulating the expression of iNOS and COX-2 was determined here. The expression of iNOS and COX-2 in macrophages was induced by YPFS, and this activation was partially blocked by the NF-κB-specific inhibitor BAY 11-7082, indicating a role of NF-κB signaling. These YPFS-induced changes in gene regulation strongly suggest that the anti-inflammatory effects of YPFS are mediated through the regulation of inflammatory enzymes.",2014 Jun 26,"['Du, Crystal Y. Q.', 'Choi, Roy C. Y.', 'Dong, Tina T. X.', 'Lau, David T. W.', 'Tsim, Karl W. K.']",PLoS One,,,True
fa16032841f11e0924b539d21444915e3bcc9a0e,PMC,A Nucleic-Acid Hydrolyzing Single Chain Antibody Confers Resistance to DNA Virus Infection in HeLa Cells and C57BL/6 Mice,http://dx.doi.org/10.1371/journal.ppat.1004208,PMC4072776,24968358,CC BY,"Viral protein neutralizing antibodies have been developed but they are limited only to the targeted virus and are often susceptible to antigenic drift. Here, we present an alternative strategy for creating virus-resistant cells and animals by ectopic expression of a nucleic acid hydrolyzing catalytic 3D8 single chain variable fragment (scFv), which has both DNase and RNase activities. HeLa cells (SCH7072) expressing 3D8 scFv acquired significant resistance to DNA viruses. Virus challenging with Herpes simplex virus (HSV) in 3D8 scFv transgenic cells and fluorescence resonance energy transfer (FRET) assay based on direct DNA cleavage analysis revealed that the induced resistance in HeLa cells was acquired by the nucleic acid hydrolyzing catalytic activity of 3D8 scFv. In addition, pseudorabies virus (PRV) infection in WT C57BL/6 mice was lethal, whereas transgenic mice (STG90) that expressed high levels of 3D8 scFv mRNA in liver, muscle, and brain showed a 56% survival rate 5 days after PRV intramuscular infection. The antiviral effects against DNA viruses conferred by 3D8 scFv expression in HeLa cells as well as an in vivo mouse system can be attributed to the nuclease activity that inhibits viral genome DNA replication in the nucleus and/or viral mRNA translation in the cytoplasm. Our results demonstrate that the nucleic-acid hydrolyzing activity of 3D8 scFv confers viral resistance to DNA viruses in vitro in HeLa cells and in an in vivo mouse system.",2014 Jun 26,"['Lee, Gunsup', 'Yu, Jaelim', 'Cho, Seungchan', 'Byun, Sung-June', 'Kim, Dae Hyun', 'Lee, Taek-Kyun', 'Kwon, Myung-Hee', 'Lee, Sukchan']",PLoS Pathog,,,True
6a6327ac7ce00c6d5b2bffd0ff65c8476d94760b,PMC,Proof by synthesis of Tobacco mosaic virus,http://dx.doi.org/10.1186/gb-2014-15-5-r67,PMC4072989,24887356,CC BY,"BACKGROUND: Synthetic biology is a discipline that includes making life forms artificially from chemicals. Here, a DNA molecule was enzymatically synthesized in vitro from DNA templates made from oligonucleotides representing the text of the first Tobacco mosaic virus (TMV) sequence elucidated in 1982. No infectious DNA molecule of that seminal reference sequence exists, so the goal was to synthesize it and then build viral chimeras. RESULTS: RNA was transcribed from synthetic DNA and encapsidated with capsid protein in vitro to make synthetic virions. Plants inoculated with the virions did not develop symptoms. When two nucleotide mutations present in the original sequence, but not present in most other TMV sequences in GenBank, were altered to reflect the consensus, the derivative synthetic virions produced classic TMV symptoms. Chimeras were then made by exchanging TMV capsid protein DNA with Tomato mosaic virus (ToMV) and Barley stripe mosaic virus (BSMV) capsid protein DNA. Virus expressing ToMV capsid protein exhibited altered, ToMV-like symptoms in Nicotiana sylvestris. A hybrid ORF6 protein unknown to nature, created by substituting the capsid protein genes in the virus, was found to be a major symptom determinant in Nicotiana benthamiana. Virus expressing BSMV capsid protein did not have an extended host range to barley, but did produce novel symptoms in N. benthamiana. CONCLUSIONS: This first report of the chemical synthesis and artificial assembly of a plant virus corrects a long-standing error in the TMV reference genome sequence and reveals that unnatural hybrid virus proteins can alter symptoms unexpectedly.",2014 Apr 30,"Cooper, Bret",Genome Biol,,,True
7e216d0c059fbbc7cace4a9d12a48482ad781366,PMC,A Multi-Method Approach to Curriculum Development for In-Service Training in China’s Newly Established Health Emergency Response Offices,http://dx.doi.org/10.1371/journal.pone.0100892,PMC4074095,24971602,CC BY,"OBJECTIVE: To describe an innovative approach for developing and implementing an in-service curriculum in China for staff of the newly established health emergency response offices (HEROs), and that is generalisable to other settings. METHODS: The multi-method training needs assessment included reviews of the competency domains needed to implement the International Health Regulations (2005) as well as China’s policies and emergency regulations. The review, iterative interviews and workshops with experts in government, academia, the military, and with HERO staff were reviewed critically by an expert technical advisory panel. FINDINGS: Over 1600 participants contributed to curriculum development. Of the 18 competency domains identified as essential for HERO staff, nine were developed into priority in-service training modules to be conducted over 2.5 weeks. Experts from academia and experienced practitioners prepared and delivered each module through lectures followed by interactive problem-solving exercises and desktop simulations to help trainees apply, experiment with, and consolidate newly acquired knowledge and skills. CONCLUSION: This study adds to the emerging literature on China’s enduring efforts to strengthen its emergency response capabilities since the outbreak of SARS in 2003. The multi-method approach to curriculum development in partnership with senior policy-makers, researchers, and experienced practitioners can be applied in other settings to ensure training is responsive and customized to local needs, resources and priorities. Ongoing curriculum development should reflect international standards and be coupled with the development of appropriate performance support systems at the workplace for motivating staff to apply their newly acquired knowledge and skills effectively and creatively.",2014 Jun 27,"['Wang, Yadong', 'Li, Xiangrui', 'Yuan, Yiwen', 'Patel, Mahomed S.']",PLoS One,,,True
53c2f84a60048a66e83bd25c1521e7bc87efd5f4,PMC,Discovery of Novel GPVI Receptor Antagonists by Structure-Based Repurposing,http://dx.doi.org/10.1371/journal.pone.0101209,PMC4074120,24971515,CC BY,"Inappropriate platelet aggregation creates a cardiovascular risk that is largely managed with thienopyridines and aspirin. Although effective, these drugs carry risks of increased bleeding and drug ‘resistance’, underpinning a drive for new antiplatelet agents. To discover such drugs, one strategy is to identify a suitable druggable target and then find small molecules that modulate it. A good and unexploited target is the platelet collagen receptor, GPVI, which promotes thrombus formation. To identify inhibitors of GPVI that are safe and bioavailable, we docked a FDA-approved drug library into the GPVI collagen-binding site in silico. We now report that losartan and cinanserin inhibit GPVI-mediated platelet activation in a selective, competitive and dose-dependent manner. This mechanism of action likely underpins the cardioprotective effects of losartan that could not be ascribed to its antihypertensive effects. We have, therefore, identified small molecule inhibitors of GPVI-mediated platelet activation, and also demonstrated the utility of structure-based repurposing.",2014 Jun 27,"['Taylor, Lewis', 'Vasudevan, Sridhar R.', 'Jones, Chris I.', 'Gibbins, Jonathan M.', 'Churchill, Grant C.', 'Campbell, R. Duncan', 'Coxon, Carmen H.']",PLoS One,,,True
7b96a98291fe154a1abf59e93e00f52ac9ac230b,PMC,Alphavirus-Based Vaccines,http://dx.doi.org/10.3390/v6062392,PMC4074933,24937089,CC BY,"Alphavirus vectors have demonstrated high levels of transient heterologous gene expression both in vitro and in vivo and, therefore, possess attractive features for vaccine development. The most commonly used delivery vectors are based on three single-stranded encapsulated alphaviruses, namely Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus. Alphavirus vectors have been applied as replication-deficient recombinant viral particles and, more recently, as replication-proficient particles. Moreover, in vitro transcribed RNA, as well as layered DNA vectors have been applied for immunization. A large number of highly immunogenic viral structural proteins expressed from alphavirus vectors have elicited strong neutralizing antibody responses in multispecies animal models. Furthermore, immunization studies have demonstrated robust protection against challenges with lethal doses of virus in rodents and primates. Similarly, vaccination with alphavirus vectors expressing tumor antigens resulted in prophylactic protection against challenges with tumor-inducing cancerous cells. As certain alphaviruses, such as Chikungunya virus, have been associated with epidemics in animals and humans, attention has also been paid to the development of vaccines against alphaviruses themselves. Recent progress in alphavirus vector development and vaccine technology has allowed conducting clinical trials in humans.",2014 Jun 16,"Lundstrom, Kenneth",Viruses,,,True
e5b3fc64db01648fa06f51f1cde95ff3d0925607,PMC,Influenza and Other Respiratory Viruses Involved in Severe Acute Respiratory Disease in Northern Italy during the Pandemic and Postpandemic Period (2009–2011),http://dx.doi.org/10.1155/2014/241298,PMC4075074,25013770,CC BY,"Since 2009 pandemic, international health authorities recommended monitoring severe and complicated cases of respiratory disease, that is, severe acute respiratory infection (SARI) and acute respiratory distress syndrome (ARDS). We evaluated the proportion of SARI/ARDS cases and deaths due to influenza A(H1N1)pdm09 infection and the impact of other respiratory viruses during pandemic and postpandemic period (2009–2011) in northern Italy; additionally we searched for unknown viruses in those cases for which diagnosis remained negative. 206 respiratory samples were collected from SARI/ARDS cases and analyzed by real-time RT-PCR/PCR to investigate influenza viruses and other common respiratory pathogens; also, a virus discovery technique (VIDISCA-454) was applied on those samples tested negative to all pathogens. Influenza A(H1N1)pdm09 virus was detected in 58.3% of specimens, with a case fatality rate of 11.3%. The impact of other respiratory viruses was 19.4%, and the most commonly detected viruses were human rhinovirus/enterovirus and influenza A(H3N2). VIDISCA-454 enabled the identification of one previously undiagnosed measles infection. Nearly 22% of SARI/ARDS cases did not obtain a definite diagnosis. In clinical practice, great efforts should be dedicated to improving the diagnosis of severe respiratory disease; the introduction of innovative molecular technologies, as VIDISCA-454, will certainly help in reducing such “diagnostic gap.”",2014 Jun 12,"['Pariani, Elena', 'Martinelli, Marianna', 'Canuti, Marta', 'Jazaeri Farsani, Seyed Mohammad', 'Oude Munnink, Bas B.', 'Deijs, Martin', 'Tanzi, Elisabetta', 'Zanetti, Alessandro', 'van der Hoek, Lia', 'Amendola, Antonella']",Biomed Res Int,,,True
ba502a88e3f83aa9e3d5edd649970db6da85c5bf,PMC,The role of CXCL10 in the pathogenesis of experimental septic shock,http://dx.doi.org/10.1186/cc13902,PMC4075230,24890566,CC BY,"INTRODUCTION: The chemokine CXCL10 is produced during infection and inflammation to activate the chemokine receptor CXCR3, an important regulator of lymphocyte trafficking and activation. The goal of this study was to assess the contributions of CXCL10 to the pathogenesis of experimental septic shock in mice. METHODS: Septic shock was induced by cecal ligation and puncture (CLP) in mice resuscitated with lactated Ringer’s solution and, in some cases, the broad spectrum antibiotic Primaxin. Studies were performed in CXCL10 knockout mice and mice treated with anti-CXCL10 immunoglobulin G (IgG). Endpoints included leukocyte trafficking and activation, core body temperature, plasma cytokine concentrations, bacterial clearance and survival. RESULTS: CXCL10 was present at high concentrations in plasma and peritoneal cavity during CLP-induced septic shock. Survival was significantly improved in CXCL10 knockout (CXCL10KO) mice and mice treated with anti-CXCL10 IgG compared to controls. CXCL10KO mice and mice treated with anti-CXCL10 IgG showed attenuated hypothermia, lower concentrations of interleukin-6 (IL-6) and macrophage inhibitory protein-2 (MIP-2) in plasma and lessened natural killer (NK) cell activation compared to control mice. Compared to control mice, bacterial burden in blood and lungs was lower in CXCL10-deficient mice but not in mice treated with anti-CXCL10 IgG. Treatment of mice with anti-CXCL10 IgG plus fluids and Primaxin at 2 or 6 hours after CLP significantly improved survival compared to mice treated with non-specific IgG under the same conditions. CONCLUSIONS: CXCL10 plays a role in the pathogenesis of CLP-induced septic shock and could serve as a therapeutic target during the acute phase of septic shock.",2014 Jun 2,"['Herzig, Daniela S', 'Luan, Liming', 'Bohannon, Julia K', 'Toliver-Kinsky, Tracy E', 'Guo, Yin', 'Sherwood, Edward R']",Crit Care,,,True
2a3a08fcd21eb4e6ed6251960b7e1e6cf1a7f18a,PMC,"Pandemic clinical case definitions are non-specific: multiple respiratory viruses circulating in the early phases of the 2009 influenza pandemic in New South Wales, Australia",http://dx.doi.org/10.1186/1743-422X-11-113,PMC4076060,24942807,CC BY,"BACKGROUND: During the early phases of the 2009 pandemic, subjects with influenza-like illness only had laboratory testing specific for the new A(H1N1)pdm09 virus. FINDINGS: Between 25(th) May and 7(th) June 2009, during the pandemic CONTAIN phase, A(H1N1)pdm09 virus was detected using nucleic acid tests in only 56 of 1466 (3.8%) samples meeting the clinical case definition required for A(H1N1)pdm09 testing. Two hundred and fifty-five randomly selected A(H1N1)pdm09 virus-negative samples were tested for other respiratory viruses using a real-time multiplex PCR assay. Of the 255 samples tested, 113 (44.3%) had other respiratory viruses detected: rhinoviruses 63.7%, seasonal influenza A 17.6%, respiratory syncytial virus 7.9%, human metapneumovirus 5.3%, parainfluenzaviruses 4.4%, influenza B virus 4.4%, and enteroviruses 0.8%. Viral co-infections were present in 4.3% of samples. CONCLUSIONS: In the very early stages of a new pandemic, limiting testing to only the novel virus will miss other clinically important co-circulating respiratory pathogens.",2014 Jun 18,"['Ratnamohan, Vigneswary Mala', 'Taylor, Janette', 'Zeng, Frank', 'McPhie, Kenneth', 'Blyth, Christopher C', 'Adamson, Sheena', 'Kok, Jen', 'Dwyer, Dominic E']",Virol J,,,True
9c2755f8ae42badb521b1c6afcb99874d21657e5,PMC,Comparison and Analysis of Biological Agent Category Lists Based On Biosafety and Biodefense,http://dx.doi.org/10.1371/journal.pone.0101163,PMC4076228,24979754,CC BY,"Biological agents pose a serious threat to human health, economic development, social stability and even national security. The classification of biological agents is a basic requirement for both biosafety and biodefense. We compared and analyzed the Biological Agent Laboratory Biosafety Category list and the defining criteria according to the World Health Organization (WHO), the National Institutes of Health (NIH), the European Union (EU) and China. We also compared and analyzed the Biological Agent Biodefense Category list and the defining criteria according to the Centers for Disease Control and Prevention (CDC) of the United States, the EU and Russia. The results show some inconsistencies among or between the two types of category lists and criteria. We suggest that the classification of biological agents based on laboratory biosafety should reduce the number of inconsistencies and contradictions. Developing countries should also produce lists of biological agents to direct their development of biodefense capabilities.To develop a suitable biological agent list should also strengthen international collaboration and cooperation.",2014 Jun 30,"['Tian, Deqiao', 'Zheng, Tao']",PLoS One,,,True
25b38d2f44283253d1e8d320c8389c069c5ae906,PMC,HIV-1 and Its gp120 Inhibits the Influenza A(H1N1)pdm09 Life Cycle in an IFITM3-Dependent Fashion,http://dx.doi.org/10.1371/journal.pone.0101056,PMC4076258,24978204,CC BY,"HIV-1-infected patients co-infected with A(H1N1)pdm09 surprisingly presented benign clinical outcome. The knowledge that HIV-1 changes the host homeostatic equilibrium, which may favor the patient resistance to some co-pathogens, prompted us to investigate whether HIV-1 infection could influence A(H1N1)pdm09 life cycle in vitro. We show here that exposure of A(H1N1)pdm09-infected epithelial cells to HIV-1 viral particles or its gp120 enhanced by 25% the IFITM3 content, resulting in a decrease in influenza replication. This event was dependent on toll-like receptor 2 and 4. Moreover, knockdown of IFITM3 prevented HIV-1 ability to inhibit A(H1N1)pdm09 replication. HIV-1 infection also increased IFITM3 levels in human primary macrophages by almost 100%. Consequently, the arrival of influenza ribonucleoproteins (RNPs) to nucleus of macrophages was inhibited, as evaluated by different approaches. Reduction of influenza RNPs entry into the nucleus tolled A(H1N1)pdm09 life cycle in macrophages earlier than usual, limiting influenza's ability to induce TNF-α. As judged by analysis of the influenza hemagglutin (HA) gene from in vitro experiments and from samples of HIV-1/A(H1N1)pdm09 co-infected individuals, the HIV-1-induced reduction of influenza replication resulted in delayed viral evolution. Our results may provide insights on the mechanisms that may have attenuated the clinical course of Influenza in HIV-1/A(H1N1)pdm09 co-infected patients during the recent influenza form 2009/2010.",2014 Jun 30,"['Mesquita, Milene', 'Fintelman-Rodrigues, Natalia', 'Sacramento, Carolina Q.', 'Abrantes, Juliana L.', 'Costa, Eduardo', 'Temerozo, Jairo R.', 'Siqueira, Marilda M.', 'Bou-Habib, Dumith Chequer', 'Souza, Thiago Moreno L.']",PLoS One,,,True
c66be1e891285a777b15ba49e685452fed6ee837,PMC,Differences in the tissue tropism to chicken oviduct epithelial cells between avian coronavirus IBV strains QX and B1648 are not related to the sialic acid binding properties of their spike proteins,http://dx.doi.org/10.1186/1297-9716-45-67,PMC4076756,24928425,CC BY,"The avian coronavirus (AvCoV) infectious bronchitis virus (IBV) is a major poultry pathogen. A characteristic feature of IBV is the occurrence of many different strains belonging to different serotypes, which makes a complete control of the disease by vaccinations a challenging task. Reasons for differences in the tissue tropism and pathogenicity between IBV strains, e.g. a predilection for the kidneys or the oviduct are still an open question. Strains of the QX genotype have been major pathogens in poultry flocks in Asia, Europe and other parts of the world. They are the cause of severe problems with kidney disease and reproductive tract disorders. We analysed infectivity and binding properties of the QX strain and compared them with those of the nephropathogenic strain B1648. As most IBV strains do not infect permanent cell lines and show infection only in primary chicken cells of the target organs, we developed a culture system for chicken oviduct explants. The epithelial cells of the oviduct showed a high susceptibility to infection by the QX strain and were almost resistant to infection by the nephropathogenic B1648 strain. Binding tests with isolated primary oviduct epithelial cells and soluble S1 proteins revealed that S1 proteins of two IBV strains bound with the same efficiency to oviduct epithelial cells. This attachment was sialic acid dependent, indicating that the sugar binding property of IBV spike proteins is not the limiting factor for differences in infection efficiency for the oviduct of the corresponding viruses.",2014 Jun 14,"['Mork, Ann-Kathrin', 'Hesse, Martina', 'Abd El Rahman, Sahar', 'Rautenschlein, Silke', 'Herrler, Georg', 'Winter, Christine']",Vet Res,,,True
13582a5cf358e261c5f432ea1abc513ae637e3dc,PMC,Differences in the tissue tropism to chicken oviduct epithelial cells between avian coronavirus IBV strains QX and B1648 are not related to the sialic acid binding properties of their spike proteins,http://dx.doi.org/10.1186/1297-9716-45-67,PMC4076756,24928425,CC BY,"The avian coronavirus (AvCoV) infectious bronchitis virus (IBV) is a major poultry pathogen. A characteristic feature of IBV is the occurrence of many different strains belonging to different serotypes, which makes a complete control of the disease by vaccinations a challenging task. Reasons for differences in the tissue tropism and pathogenicity between IBV strains, e.g. a predilection for the kidneys or the oviduct are still an open question. Strains of the QX genotype have been major pathogens in poultry flocks in Asia, Europe and other parts of the world. They are the cause of severe problems with kidney disease and reproductive tract disorders. We analysed infectivity and binding properties of the QX strain and compared them with those of the nephropathogenic strain B1648. As most IBV strains do not infect permanent cell lines and show infection only in primary chicken cells of the target organs, we developed a culture system for chicken oviduct explants. The epithelial cells of the oviduct showed a high susceptibility to infection by the QX strain and were almost resistant to infection by the nephropathogenic B1648 strain. Binding tests with isolated primary oviduct epithelial cells and soluble S1 proteins revealed that S1 proteins of two IBV strains bound with the same efficiency to oviduct epithelial cells. This attachment was sialic acid dependent, indicating that the sugar binding property of IBV spike proteins is not the limiting factor for differences in infection efficiency for the oviduct of the corresponding viruses.",2014 Jun 14,"['Mork, Ann-Kathrin', 'Hesse, Martina', 'Abd El Rahman, Sahar', 'Rautenschlein, Silke', 'Herrler, Georg', 'Winter, Christine']",Vet Res,,,False
5752683f35a4f922c8a1a363c93dcae050b92b50,PMC,How to Reduce the Latent Social Risk of Disease: The Determinants of Vaccination against Rabies in Taiwan,http://dx.doi.org/10.3390/ijerph110605934,PMC4078556,24901413,CC BY,"To control the latent social risk of disease, the government usually spreads accurate information and attempts to improve the public’s attitude toward adopting prevention. However, these methods with the Knowledge, Attitudes, and Practices (KAP) model do not always work. Therefore, we used the theory of planned behavior (TPB) to understand dog owners’ behavior and distinguished the knowledge effect as objective knowledge (OK) and subjective knowledge (SK). A total of 310 dog owners completed a questionnaire based on our model. We employed structural equation modeling to verify the structural relationships and found three main results. First, our model was fit, and each path was significant. People with better attitudes, stronger subjective norms, and more perceptive behavioral control have stronger behavioral intention. Second, perceived behavioral control, not attitude, was the best predictive index in this model. Finally, on perceived behavioral control, subjective knowledge showed more influence than objective knowledge. We successfully extended TPB to explain the behavioral intention of dog owners and presented more workable recommendations. To reduce the latent social risk of disease, the government should not only address dog owners’ attitudes, but also their subjective norms and perceptive behavioral control. Indeed, perceptive behavioral control and SK showed the most influence in this model. It is implied that the self-efficacy of dog owners is the most important factor in such a behavior. Therefore, the government should focus on enhancing dog owners’ self-efficacy first while devoted to prevention activities.",2014 Jun 4,"['Ku-Yuan, Lee', 'Li-Chi, Lan', 'Jiun-Hao, Wang', 'Chen-Ling, Fang', 'Kun-Sun, Shiao']",Int J Environ Res Public Health,,,True
b6c62ca4653ef469da8a131bcd9fe168e439e3a3,PMC,A Comprehensive Phylogenetic and Structural Analysis of the Carcinoembryonic Antigen (CEA) Gene Family,http://dx.doi.org/10.1093/gbe/evu103,PMC4079198,24858421,CC BY,"The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin (Ig) superfamily and codes for a vast number of glycoproteins that differ greatly both in amino acid composition and function. The CEA family is divided into two groups, the carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) and the pregnancy-specific glycoproteins. The CEA family members are implicated in pleiotropic (patho)physiological functions including cell–cell adhesion, pregnancy, immunity, neovascularization, regulation of insulin homeostasis, and carcinogenesis. In general, the CEA-encoded proteins are composed of an extracellular region with Ig variable and constant-like domains and a cytoplasmic region containing signaling motifs. Of particular interest, the well-studied human and mouse CEA genes are arranged in clusters in a single chromosome. Taking into account this characteristic, we made an effort to reconstruct the evolutionary history of the CEA gene family. Toward this end, the publicly available genomes were searched extensively for CEA homologs. The domain organization of the retrieved protein sequences was analyzed, and, subsequently, comprehensive phylogenetic analyses of the entire length CEA homologous proteins were performed. A series of evolutionarily conserved amino acid residues, functionally important, were identified. The relative positioning of these residues on the modeled tertiary structure of novel CEA protein domains revealed that they are, also, spatially conserved. Furthermore, the chromosomal arrangement of CEA genes was examined, and it was found that the CEA genes are preserved in terms of position, transcriptional orientation, and number in all species under investigation.",2014 May 23,"['Pavlopoulou, Athanasia', 'Scorilas, Andreas']",Genome Biol Evol,,,True
4660da2a8603d28150c9d3de1a17c0333094087c,PMC,Histopathology of Pneumocystis carinii pneumonia in immunocompetent laboratory rats,http://dx.doi.org/10.3892/etm.2014.1732,PMC4079405,25009598,CC BY,"The occurrence of idiopathic pulmonary lesions in laboratory rats, characterized by lymphohistiocytic interstitial pneumonia with dense perivascular lymphoid cuffs, has been reported over the past decade. Although the term rat respiratory virus (RRV) was adopted to confer a putative viral etiology to the idiopathic pulmonary lesions, the etiology of this disease remains to be elucidated. Recently, inflammatory lesions have been observed in the lungs of immunocompetent laboratory rats similar to those previously described. Based on the latest evidence indicating that Pneumocystis carinii (P. carinii), and not putative RRV, causes infectious interstitial pneumonia in laboratory rats, the present study investigated whether the pulmonary lesions observed were caused by P. carinii infection. Male Sprague-Dawley rats, free of known pathogens, were introduced into a rat colony positive for RRV-type lesions. Routine histopathological examinations were performed on the rat lung tissues following exposure. The presence of Pneumocystis organisms was confirmed using Grocott’s methenamine silver (GMS) staining. At week 3 following introduction, a few small lymphoid aggregates were located adjacent to the edematous vascular sheath. By week 5, foci of dense perivascular lymphoid cuffing were observed. Multifocal lymphohistiocytic interstitial pneumonia and prominent lymphoid perivascular cuffs were observed between week 7 and 10. GMS staining confirmed the presence of Pneumocystis cysts. Thus, the results of the present study demonstrated that P. carinii caused lymphohistiocytic interstitial pneumonia in a group of laboratory rats. The observations strongly support the conclusion that P. carinii infection in immunocompetent laboratory rats causes the lung lesions that were previously attributed to RRV.",2014 Aug 26,"['KIM, HYUN-SOO', 'DO, SUNG-IM', 'KIM, YOUN WHA']",Exp Ther Med,,,True
ff77d5ebc39274bb7729f2b5261bca574bdfd6a8,PMC,"Prevalence and Genetic Diversity Analysis of Human Coronavirus OC43 among Adult Patients with Acute Respiratory Infections in Beijing, 2012",http://dx.doi.org/10.1371/journal.pone.0100781,PMC4079595,24987849,CC BY,"To determine the prevalence, epidemiology and genetic diversity of human coronavirus OC43 (HCoV-OC43) among adult patients with acute respiratory infections (ARI) in Beijing,five hundred and fifty-nine nasopharyngeal swab samples were collected from adult patients with ARI in Beijing. The prevalence of HCoV-OC43 infection among these patients was assessed using two different OneStep reverse transcription polymerase chain reaction (RT-PCR) assays. The epidemiological profiles of the patients with HCoV-OC43 infection were described. Partial S and N genes of HCoV-OC43 circulating strains were sequenced followed by phylogenetic analysis and amino acid alignment. Our results showed that the prevalence of HCoV-OC43 infection was 12.52% (95% CI: 9.78–15.26%), and the epidemic peak occurred in autumn. Fifty partial S and 40 partial N fragments were obtained from these patients. Phylogenetic analysis based on neighbour-joining method showed that at least three distinct clusters (A, B, C/D) of HCoV-OC43 strains were circulating among adult patients with ARI in Beijing. In addition, some novel unique clusters (UNT) of HCoV-OC43 were found in the S- and N-based phylogenetic trees. Furthermore, consensus amino acids substitutes for each cluster were also found after alignment of partial S or N sequence coding region in this study. In conclusion, we herein describe the prevalence of HCoV-OC43 among adult patients and provide substantial evidence for the genetic diversity of HCoV-OC43 circulating in Beijing.",2014 Jul 2,"['Hu, Qin', 'Lu, Roujian', 'Peng, Kun', 'Duan, Xijie', 'Wang, Yanqun', 'Zhao, Yanjie', 'Wang, Wen', 'Lou, Yongliang', 'Tan, Wenjie']",PLoS One,,,True
36eedeee8fd40eda2f7f1d0c0cb0e2a4971439a6,PMC,"After Malaria Is Controlled, What's Next?†",http://dx.doi.org/10.4269/ajtmh.14-0056,PMC4080571,24591436,CC BY,,2014 Jul 2,"Walker, David H.",Am J Trop Med Hyg,,,True
40ae6bae0a5f86ac9beb57de189ae3320875e22c,PMC,ERAD and how viruses exploit it,http://dx.doi.org/10.3389/fmicb.2014.00330,PMC4080680,25071743,CC BY,"Endoplasmic reticulum (ER)-associated degradation (ERAD) is a universally important process among eukaryotic cells. ERAD is necessary to preserve cell integrity since the accumulation of defective proteins results in diseases associated with neurological dysfunction, cancer, and infections. This process involves recognition of misfolded or misassembled proteins that have been translated in association with ER membranes. Recognition of ERAD substrates leads to their extraction through the ER membrane (retrotranslocation or dislocation), ubiquitination, and destruction by cytosolic proteasomes. This review focuses on ERAD and its components as well as how viruses use this process to promote their replication and to avoid the immune response.",2014 Jul 3,"['Byun, Hyewon', 'Gou, Yongqiang', 'Zook, Adam', 'Lozano, Mary M.', 'Dudley, Jaquelin P.']",Front Microbiol,,,True
dcd7287d538d38848896654f8dd359f9adf94946,PMC,Advances in Diagnosis of Respiratory Diseases of Small Ruminants,http://dx.doi.org/10.1155/2014/508304,PMC4082846,25028620,CC BY,"Irrespective of aetiology, infectious respiratory diseases of sheep and goats contribute to 5.6 percent of the total diseases of small ruminants. These infectious respiratory disorders are divided into two groups: the diseases of upper respiratory tract, namely, nasal myiasis and enzootic nasal tumors, and diseases of lower respiratory tract, namely, peste des petits ruminants (PPR), parainfluenza, Pasteurellosis, Ovine progressive pneumonia, mycoplasmosis, caprine arthritis encephalitis virus, caseous lymphadenitis, verminous pneumonia, and many others. Depending upon aetiology, many of them are acute and fatal in nature. Early, rapid, and specific diagnosis of such diseases holds great importance to reduce the losses. The advanced enzyme-linked immunosorbent assays (ELISAs) for the detection of antigen as well as antibodies directly from the samples and molecular diagnostic assays along with microsatellites comprehensively assist in diagnosis as well as treatment and epidemiological studies. The present review discusses the advancements made in the diagnosis of common infectious respiratory diseases of sheep and goats. It would update the knowledge and help in adapting and implementing appropriate, timely, and confirmatory diagnostic procedures. Moreover, it would assist in designing appropriate prevention protocols and devising suitable control strategies to overcome respiratory diseases and alleviate the economic losses.",2014 Jun 15,"['Chakraborty, Sandip', 'Kumar, Amit', 'Tiwari, Ruchi', 'Rahal, Anu', 'Malik, Yash', 'Dhama, Kuldeep', 'Pal, Amar', 'Prasad, Minakshi']",Vet Med Int,,,True
af6cc29d9bc7f9d84ded3d7ad30509a945e425d3,PMC,Metagenomic analysis of a sample from a patient with respiratory tract infection reveals the presence of a γ-papillomavirus,http://dx.doi.org/10.3389/fmicb.2014.00347,PMC4086198,25071755,CC BY,"Previously unknown or unexpected pathogens may be responsible for that proportion of respiratory diseases in which a causative agent cannot be identified. The application of broad-spectrum, sequence independent virus discovery techniques may be useful to reduce this proportion and widen our knowledge about respiratory pathogens. Thanks to the availability of high-throughput sequencing (HTS) technology, it became today possible to detect viruses which are present at a very low load, but the clinical relevance of those viruses must be investigated. In this study we used VIDISCA-454, a restriction enzyme based virus discovery method that utilizes Roche 454 HTS system, on a nasal swab collected from a subject with respiratory complaints. A γ-papillomavirus was detected (complete genome: 7142 bp) and its role in disease was investigated. Respiratory samples collected both during the acute phase of the illness and 2 weeks after full recovery contained the virus. The patient presented antibodies directed against the virus but there was no difference between IgG levels in blood samples collected during the acute phase and 2 weeks after full recovery. We therefore concluded that the detected γ-papillomavirus is unlikely to be the causative agent of the respiratory complaints and its presence in the nose of the patient is not related to the disease. Although HTS based virus discovery techniques proved their great potential as a tool to clarify the etiology of some infectious diseases, the obtained information must be subjected to cautious interpretations. This study underlines the crucial importance of performing careful investigations on viruses identified when applying sensitive virus discovery techniques, since the mere identification of a virus and its presence in a clinical sample are not satisfactory proofs to establish a causative link with a disease.",2014 Jul 8,"['Canuti, Marta', 'Deijs, Martin', 'Jazaeri Farsani, Seyed M.', 'Holwerda, Melle', 'Jebbink, Maarten F.', 'de Vries, Michel', 'van Vugt, Saskia', 'Brugman, Curt', 'Verheij, Theo', 'Lammens, Christine', 'Goossens, Herman', 'Loens, Katherine', 'Ieven, Margareta', 'van der Hoek, Lia']",Front Microbiol,,,True
0542a6ae26f57a5ffa35dcfebdec5004ff45688c,PMC,Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies,http://dx.doi.org/10.1371/journal.pone.0101785,PMC4086938,25004134,CC0,"BACKGROUND: Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients. METHODS AND FINDINGS: Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17 countries at 2 days (IQR 1–3) and 6 days (IQR 4–10) following ILI onset, respectively. Disease progression was experienced by 29 (1 death) outpatients (5.1%; 95% CI: 3.4–7.2%) and 80 inpatients [death (32), hospitalization >28 days (43) or ICU transfer (20)] (21.6%; 95% CI: 17.5–26.2%). Disease progression (death) for hospitalized patients was 53.1% (26.6%) and 12.8% (3.8%), respectively, for those enrolled in the ICU and general ward. In pooled analyses for both studies, predictors of disease progression were age, longer duration of symptoms at enrollment and immunosuppression. Patients hospitalized during the pandemic period had a poorer prognosis than in subsequent seasons. CONCLUSIONS: Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection. These data reinforce the need for international trials of novel treatment strategies for influenza infection and serve as a reminder of the need to monitor the severity of seasonal and pandemic influenza epidemics globally. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: FLU 002- NCT01056354, FLU 003- NCT01056185.",2014 Jul 8,"['Lynfield, Ruth', 'Davey, Richard', 'Dwyer, Dominic E.', 'Losso, Marcelo H.', 'Wentworth, Deborah', 'Cozzi-Lepri, Alessandro', 'Herman-Lamin, Kathy', 'Cholewinska, Grazyna', 'David, Daniel', 'Kuetter, Stefan', 'Ternesgen, Zelalem', 'Uyeki, Timothy M.', 'Lane, H. Clifford', 'Lundgren, Jens', 'Neaton, James D.', None]",PLoS One,,,True
403d1861771bf1e5e3625b0f86247d7134c3873d,PMC,Pandemic preparedness: perceptions of vulnerable migrants in Thailand towards WHO-recommended non-pharmaceutical interventions: a cross-sectional study,http://dx.doi.org/10.1186/1471-2458-14-665,PMC4090173,24973943,CC BY,"BACKGROUND: Non-pharmaceutical interventions (NPIs) constituted the principal public health response to the previous influenza A (H1N1) 2009 pandemic and are one key area of ongoing preparation for future pandemics. Thailand is an important point of focus in terms of global pandemic preparedness and response due to its role as the major transportation hub for Southeast Asia, the endemic presence of multiple types of influenza, and its role as a major receiving country for migrants. Our aim was to collect information about vulnerable migrants’ perceptions of and ability to implement NPIs proposed by the WHO. We hope that this information will help us to gauge the capacity of this population to engage in pandemic preparedness and response efforts, and to identify potential barriers to NPI effectiveness. METHODS: A cross-sectional survey was performed. The study was conducted during the influenza H1N1 2009 pandemic and included 801 migrant participants living in border areas thought to be high risk by the Thailand Ministry of Public Health. Data were collected by Migrant Community Health Workers using a 201-item interviewer-assisted questionnaire. Univariate descriptive analyses were conducted. RESULTS: With the exception of border measures, to which nearly all participants reported they would be adherent, attitudes towards recommended NPIs were generally negative or uncertain. Other potential barriers to NPI implementation include limited experience applying these interventions (e.g., using a thermometer, wearing a face mask) and inadequate hand washing and household disinfection practices. CONCLUSIONS: Negative or ambivalent attitudes towards NPIs combined with other barriers identified suggest that vulnerable migrants in Thailand have a limited capacity to participate in pandemic preparedness efforts. This limited capacity likely puts migrants at risk of propagating the spread of a pandemic virus. Coordinated risk communication and public education are potential strategies that may reduce barriers to individual NPI implementation.",2014 Jun 28,"['Hickey, Jason', 'Gagnon, Anita J', 'Jitthai, Nigoon']",BMC Public Health,,,True
3b2a2a17eb789fee6c46ff6cdc7b6e794f7d545c,PMC,Epidemic Surveillance Using an Electronic Medical Record: An Empiric Approach to Performance Improvement,http://dx.doi.org/10.1371/journal.pone.0100845,PMC4090236,25006878,CC0,"BACKGROUNDS: Electronic medical records (EMR) form a rich repository of information that could benefit public health. We asked how structured and free-text narrative EMR data should be combined to improve epidemic surveillance for acute respiratory infections (ARI). METHODS: Eight previously characterized ARI case detection algorithms (CDA) were applied to historical EMR entries to create authentic time series of daily ARI case counts (background). An epidemic model simulated influenza cases (injection). From the time of the injection, cluster-detection statistics were applied daily on paired background+injection (combined) and background-only time series. This cycle was then repeated with the injection shifted to each week of the evaluation year. We computed: a) the time from injection to the first statistical alarm uniquely found in the combined dataset (Detection Delay); b) how often alarms originated in the background-only dataset (false-alarm rate, or FAR); and c) the number of cases found within these false alarms (Caseload). For each CDA, we plotted the Detection Delay as a function of FAR or Caseload, over a broad range of alarm thresholds. RESULTS: CDAs that combined text analyses seeking ARI symptoms in clinical notes with provider-assigned diagnostic codes in order to maximize the precision rather than the sensitivity of case-detection lowered Detection Delay at any given FAR or Caseload. CONCLUSION: An empiric approach can guide the integration of EMR data into case-detection methods that improve both the timeliness and efficiency of epidemic detection.",2014 Jul 9,"['Zheng, Hongzhang', 'Gaff, Holly', 'Smith, Gary', 'DeLisle, Sylvain']",PLoS One,,,True
e023845ba693ca1f8667d37d40b02626a6c2ecd5,PMC,On the Use of Human Mobility Proxies for Modeling Epidemics,http://dx.doi.org/10.1371/journal.pcbi.1003716,PMC4091706,25010676,CC BY,"Human mobility is a key component of large-scale spatial-transmission models of infectious diseases. Correctly modeling and quantifying human mobility is critical for improving epidemic control, but may be hindered by data incompleteness or unavailability. Here we explore the opportunity of using proxies for individual mobility to describe commuting flows and predict the diffusion of an influenza-like-illness epidemic. We consider three European countries and the corresponding commuting networks at different resolution scales, obtained from (i) official census surveys, (ii) proxy mobility data extracted from mobile phone call records, and (iii) the radiation model calibrated with census data. Metapopulation models defined on these countries and integrating the different mobility layers are compared in terms of epidemic observables. We show that commuting networks from mobile phone data capture the empirical commuting patterns well, accounting for more than 87% of the total fluxes. The distributions of commuting fluxes per link from mobile phones and census sources are similar and highly correlated, however a systematic overestimation of commuting traffic in the mobile phone data is observed. This leads to epidemics that spread faster than on census commuting networks, once the mobile phone commuting network is considered in the epidemic model, however preserving to a high degree the order of infection of newly affected locations. Proxies' calibration affects the arrival times' agreement across different models, and the observed topological and traffic discrepancies among mobility sources alter the resulting epidemic invasion patterns. Results also suggest that proxies perform differently in approximating commuting patterns for disease spread at different resolution scales, with the radiation model showing higher accuracy than mobile phone data when the seed is central in the network, the opposite being observed for peripheral locations. Proxies should therefore be chosen in light of the desired accuracy for the epidemic situation under study.",2014 Jul 10,"['Tizzoni, Michele', 'Bajardi, Paolo', 'Decuyper, Adeline', 'Kon Kam King, Guillaume', 'Schneider, Christian M.', 'Blondel, Vincent', 'Smoreda, Zbigniew', 'González, Marta C.', 'Colizza, Vittoria']",PLoS Comput Biol,,,True
0a7a6b0343a8760e62e7b69c3eacae5c9d1eddc7,PMC,On the Use of Human Mobility Proxies for Modeling Epidemics,http://dx.doi.org/10.1371/journal.pcbi.1003716,PMC4091706,25010676,CC BY,"Human mobility is a key component of large-scale spatial-transmission models of infectious diseases. Correctly modeling and quantifying human mobility is critical for improving epidemic control, but may be hindered by data incompleteness or unavailability. Here we explore the opportunity of using proxies for individual mobility to describe commuting flows and predict the diffusion of an influenza-like-illness epidemic. We consider three European countries and the corresponding commuting networks at different resolution scales, obtained from (i) official census surveys, (ii) proxy mobility data extracted from mobile phone call records, and (iii) the radiation model calibrated with census data. Metapopulation models defined on these countries and integrating the different mobility layers are compared in terms of epidemic observables. We show that commuting networks from mobile phone data capture the empirical commuting patterns well, accounting for more than 87% of the total fluxes. The distributions of commuting fluxes per link from mobile phones and census sources are similar and highly correlated, however a systematic overestimation of commuting traffic in the mobile phone data is observed. This leads to epidemics that spread faster than on census commuting networks, once the mobile phone commuting network is considered in the epidemic model, however preserving to a high degree the order of infection of newly affected locations. Proxies' calibration affects the arrival times' agreement across different models, and the observed topological and traffic discrepancies among mobility sources alter the resulting epidemic invasion patterns. Results also suggest that proxies perform differently in approximating commuting patterns for disease spread at different resolution scales, with the radiation model showing higher accuracy than mobile phone data when the seed is central in the network, the opposite being observed for peripheral locations. Proxies should therefore be chosen in light of the desired accuracy for the epidemic situation under study.",2014 Jul 10,"['Tizzoni, Michele', 'Bajardi, Paolo', 'Decuyper, Adeline', 'Kon Kam King, Guillaume', 'Schneider, Christian M.', 'Blondel, Vincent', 'Smoreda, Zbigniew', 'González, Marta C.', 'Colizza, Vittoria']",PLoS Comput Biol,,,False
e952843f8bdc91e48ca6fa5fa94d53abdfb63ff7,PMC,The Ubiquitin-Conjugating System: Multiple Roles in Viral Replication and Infection,http://dx.doi.org/10.3390/cells3020386,PMC4092849,24805990,CC BY,"Through the combined action of ubiquitinating and deubiquitinating enzymes, conjugation of ubiquitin to a target protein acts as a reversible post-translational modification functionally similar to phosphorylation. Indeed, ubiquitination is more and more recognized as a central process for the fine regulation of many cellular pathways. Due to their nature as obligate intracellular parasites, viruses rely on the most conserved host cell machineries for their own replication. Thus, it is not surprising that members from almost every viral family are challenged by ubiquitin mediated mechanisms in different steps of their life cycle and have evolved in order to by-pass or exploit the cellular ubiquitin conjugating system to maximize their chance to establish a successful infection. In this review we will present several examples of the complex interplay that links viruses and the ubiquitin conjugation machinery, with a special focus on the mechanisms evolved by the human immunodeficiency virus to escape from cellular restriction factors and to exit from infected cells.",2014 May 6,"['Calistri, Arianna', 'Munegato, Denis', 'Carli, Ilaria', 'Parolin, Cristina', 'Palù, Giorgio']",Cells,,,True
2de3df4bc6bfab602038165ccb45368768071956,PMC,Medical relevance of UK-funded non-human primate research published from January 1997 to July 2012,http://dx.doi.org/10.1177/0141076814530686,PMC4093757,24739383,CC BY,"In 2012, the Bateson Review of research using non-human primates (NHPs) recommended the commissioning of a working group to identify and follow-up the results of UK-funded NHP research of potential benefit for human health (Recommendation 4), but the Medical Research Council (MRC) has postponed implementation of the recommendation. Information on results and potential benefits of NHP research therefore remains unavailable. To fill this gap in knowledge, this study identified all published NHP research studies funded by the MRC, Wellcome Trust and Biotechnology and Biological Sciences Research Council (BBSRC) from January 1997 to July 2012 and assessed full texts for medical relevance. In total, 284 papers were identified, of which 51 (18%) involved invasive NHP research, compared to 176 (61%) which used NHP tissue and cell lines, indicating a shift in research emphasis from invasive whole animal to cell-based research. Of these studies, 98 (35%) were medically relevant, of which 22 had potential therapeutic or public health applications. The relatively low proportion of medical studies together with the small number of applied studies raises questions over the level of investment in medical research and the effectiveness of knowledge transfer from basic to applied research. Implementation of the Bateson Review’s Recommendation 4 would address these questions.",2014 Jul,"Moore, Edward",J R Soc Med,,,True
9cdbf5aaebee9f6b33cb9fbbdcd1a68d53727289,PMC,CXCR3 modulates glial accumulation and activation in cuprizone-induced demyelination of the central nervous system,http://dx.doi.org/10.1186/1742-2094-11-109,PMC4096537,24930935,CC BY,"BACKGROUND: The functional state of glial cells, like astrocytes and microglia, critically modulates the course of neuroinflammatory and neurodegenerative diseases and can have both detrimental and beneficial effects. Glial cell function is tightly controlled by cellular interactions in which cytokines are important messengers. Recent studies provide evidence that in particular chemokines are important modulators of glial cell function. During the course of CNS diseases like multiple sclerosis or Alzheimer’s disease, and in the corresponding animal models, the chemokines CXCL9 and CXCL10 are abundantly expressed at sites of glial activation, arguing for an important role of these chemokines and their corresponding receptor CXCR3 in glial activation. To clarify the role of this chemokine system in glial cell activation, we characterized the impact of CXCR3 on glial activation in a model of toxic demyelination in which glial activation without a prominent influx of hematogenous cells is prototypical. METHODS: We investigated the impact of CXCR3 on cuprizone-induced demyelination, comparing CXCR3-deficient mice with wild type controls. The clinical course during cuprizone feeding was documented for five weeks and for the subsequent four days withdrawal of the cuprizone diet (5.5 weeks). Glial activation was characterized using histological, histomorphometric and phenotypic analysis. Molecular analysis for (de)myelination and neuroinflammation was applied to characterize the effect of cuprizone on CXCR3-deficient mice and control animals. RESULTS: CXCR3-deficient mice displayed a milder clinical course during cuprizone feeding and a more rapid body weight recovery after offset of diet. In the CNS, CXCR3 deficiency significantly attenuated the accumulation and activation of microglia and astrocytes. Moreover, a deficiency of CXCR3 reduced the expression of the microglial activation markers CD45 and CD11b. Compared to controls, we observed a vast reduction of RNA levels for proinflammatory cytokines and chemokines like Ccl2, Cxcl10, Tnf and Il6 within the CNS of cuprizone-treated mice. Lastly, CXCR3 deficiency had no major effects on the course of demyelination during cuprizone feeding. CONCLUSIONS: The CXCR3 chemokine system is critically involved in the intrinsic glial activation during cuprizone-induced demyelination, which significantly modulates the distribution of glial cells and the local cytokine milieu.",2014 Jun 16,"['Krauthausen, Marius', 'Saxe, Simon', 'Zimmermann, Julian', 'Emrich, Michael', 'Heneka, Michael T', 'Müller, Marcus']",J Neuroinflammation,,,True
85e67a0122ea002985fd0e498a7f94df64957701,PMC,The use of the temporal scan statistic to detect methicillin-resistant Staphylococcus aureus clusters in a community hospital,http://dx.doi.org/10.1186/1471-2334-14-375,PMC4097048,25005247,CC BY,"BACKGROUND: In healthcare facilities, conventional surveillance techniques using rule-based guidelines may result in under- or over-reporting of methicillin-resistant Staphylococcus aureus (MRSA) outbreaks, as these guidelines are generally unvalidated. The objectives of this study were to investigate the utility of the temporal scan statistic for detecting MRSA clusters, validate clusters using molecular techniques and hospital records, and determine significant differences in the rate of MRSA cases using regression models. METHODS: Patients admitted to a community hospital between August 2006 and February 2011, and identified with MRSA > 48 hours following hospital admission, were included in this study. Between March 2010 and February 2011, MRSA specimens were obtained for spa typing. MRSA clusters were investigated using a retrospective temporal scan statistic. Tests were conducted on a monthly scale and significant clusters were compared to MRSA outbreaks identified by hospital personnel. Associations between the rate of MRSA cases and the variables year, month, and season were investigated using a negative binomial regression model. RESULTS: During the study period, 735 MRSA cases were identified and 167 MRSA isolates were spa typed. Nine different spa types were identified with spa type 2/t002 (88.6%) the most prevalent. The temporal scan statistic identified significant MRSA clusters at the hospital (n = 2), service (n = 16), and ward (n = 10) levels (P ≤ 0.05). Seven clusters were concordant with nine MRSA outbreaks identified by hospital staff. For the remaining clusters, seven events may have been equivalent to true outbreaks and six clusters demonstrated possible transmission events. The regression analysis indicated years 2009–2011, compared to 2006, and months March and April, compared to January, were associated with an increase in the rate of MRSA cases (P ≤ 0.05). CONCLUSIONS: The application of the temporal scan statistic identified several MRSA clusters that were not detected by hospital personnel. The identification of specific years and months with increased MRSA rates may be attributable to several hospital level factors including the presence of other pathogens. Within hospitals, the incorporation of the temporal scan statistic to standard surveillance techniques is a valuable tool for healthcare workers to evaluate surveillance strategies and aid in the identification of MRSA clusters.",2014 Jul 8,"['Faires, Meredith C', 'Pearl, David L', 'Ciccotelli, William A', 'Berke, Olaf', 'Reid-Smith, Richard J', 'Weese, J Scott']",BMC Infect Dis,,,True
e9f9bb005036503310d511566fbfc6b1a82d8fdd,PMC,Substitution at Aspartic Acid 1128 in the SARS Coronavirus Spike Glycoprotein Mediates Escape from a S2 Domain-Targeting Neutralizing Monoclonal Antibody,http://dx.doi.org/10.1371/journal.pone.0102415,PMC4097068,25019613,CC BY,"The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is the etiological agent for the infectious disease, SARS, which first emerged 10 years ago. SARS-CoV is a zoonotic virus that has crossed the species barriers to infect humans. Bats, which harbour a diverse pool of SARS-like CoVs (SL-CoVs), are believed to be the natural reservoir. The SARS-CoV surface Spike (S) protein is a major antigenic determinant in eliciting neutralizing antibody production during SARS-CoV infection. In our previous work, we showed that a panel of murine monoclonal antibodies (mAbs) that target the S2 subunit of the S protein are capable of neutralizing SARS-CoV infection in vitro (Lip KM et al, J Virol. 2006 Jan; 80(2): 941–50). In this study, we report our findings on the characterization of one of these mAbs, known as 1A9, which binds to the S protein at a novel epitope within the S2 subunit at amino acids 1111–1130. MAb 1A9 is a broadly neutralizing mAb that prevents viral entry mediated by the S proteins of human and civet SARS-CoVs as well as bat SL-CoVs. By generating mutant SARS-CoV that escapes the neutralization by mAb 1A9, the residue D1128 in S was found to be crucial for its interaction with mAb 1A9. S protein containing the substitution of D1128 with alanine (D1128A) exhibited a significant decrease in binding capability to mAb 1A9 compared to wild-type S protein. By using a pseudotyped viral entry assay, it was shown that the D1128A substitution in the escape virus allows it to overcome the viral entry blockage by mAb 1A9. In addition, the D1128A mutation was found to exert no effects on the S protein cell surface expression and incorporation into virion particles, suggesting that the escape virus retains the same viral entry property as the wild-type virus.",2014 Jul 14,"['Ng, Oi-Wing', 'Keng, Choong-Tat', 'Leung, Cynthia Sau-Wai', 'Peiris, J. S. Malik', 'Poon, Leo Lit Man', 'Tan, Yee-Joo']",PLoS One,,,True
fb0a470971165da64de3314623977282563c7a04,PMC,"Dissecting Virus Entry: Replication-Independent Analysis of Virus Binding, Internalization, and Penetration Using Minimal Complementation of β-Galactosidase",http://dx.doi.org/10.1371/journal.pone.0101762,PMC4099126,25025332,CC BY,"Studies of viral entry into host cells often rely on the detection of post-entry parameters, such as viral replication or the expression of a reporter gene, rather than on measuring entry per se. The lack of assays to easily detect the different steps of entry severely hampers the analysis of this key process in virus infection. Here we describe novel, highly adaptable viral entry assays making use of minimal complementation of the E. coli β-galactosidase in mammalian cells. Enzyme activity is reconstituted when a small intravirion peptide (α-peptide) is complementing the inactive mutant form ΔM15 of β-galactosidase. The method allows to dissect and to independently detect binding, internalization, and fusion of viruses during host cell entry. Here we use it to confirm and extend current knowledge on the entry process of two enveloped viruses: vesicular stomatitis virus (VSV) and murine hepatitis coronavirus (MHV).",2014 Jul 15,"['Burkard, Christine', 'Bloyet, Louis-Marie', 'Wicht, Oliver', 'van Kuppeveld, Frank J.', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.', 'Bosch, Berend Jan']",PLoS One,,,True
196eaa0045b36b7c0e56594ad4fbec1e8edd3e9c,PMC,"Dissecting Virus Entry: Replication-Independent Analysis of Virus Binding, Internalization, and Penetration Using Minimal Complementation of β-Galactosidase",http://dx.doi.org/10.1371/journal.pone.0101762,PMC4099126,25025332,CC BY,"Studies of viral entry into host cells often rely on the detection of post-entry parameters, such as viral replication or the expression of a reporter gene, rather than on measuring entry per se. The lack of assays to easily detect the different steps of entry severely hampers the analysis of this key process in virus infection. Here we describe novel, highly adaptable viral entry assays making use of minimal complementation of the E. coli β-galactosidase in mammalian cells. Enzyme activity is reconstituted when a small intravirion peptide (α-peptide) is complementing the inactive mutant form ΔM15 of β-galactosidase. The method allows to dissect and to independently detect binding, internalization, and fusion of viruses during host cell entry. Here we use it to confirm and extend current knowledge on the entry process of two enveloped viruses: vesicular stomatitis virus (VSV) and murine hepatitis coronavirus (MHV).",2014 Jul 15,"['Burkard, Christine', 'Bloyet, Louis-Marie', 'Wicht, Oliver', 'van Kuppeveld, Frank J.', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.', 'Bosch, Berend Jan']",PLoS One,,,True
a87c83a672852a6d046357d68715f3c3c0cdf5b1,PMC,Viral Metagenomics on Animals as a Tool for the Detection of Zoonoses Prior to Human Infection?,http://dx.doi.org/10.3390/ijms150610377,PMC4100157,24918293,CC BY,"Many human viral infections have a zoonotic, i.e., wild or domestic animal, origin. Several zoonotic viruses are transmitted to humans directly via contact with an animal or indirectly via exposure to the urine or feces of infected animals or the bite of a bloodsucking arthropod. If a virus is able to adapt and replicate in its new human host, human-to-human transmissions may occur, possibly resulting in an epidemic, such as the A/H1N1 flu pandemic in 2009. Thus, predicting emerging zoonotic infections is an important challenge for public health officials in the coming decades. The recent development of viral metagenomics, i.e., the characterization of the complete viral diversity isolated from an organism or an environment using high-throughput sequencing technologies, is promising for the surveillance of such diseases and can be accomplished by analyzing the viromes of selected animals and arthropods that are closely in contact with humans. In this review, we summarize our current knowledge of viral diversity within such animals (in particular blood-feeding arthropods, wildlife and domestic animals) using metagenomics and present its possible future application for the surveillance of zoonotic and arboviral diseases.",2014 Jun 10,"['Temmam, Sarah', 'Davoust, Bernard', 'Berenger, Jean-Michel', 'Raoult, Didier', 'Desnues, Christelle']",Int J Mol Sci,,,True
e1c6885ff3cb7eded9abdbbebc8e486459265c95,PMC,Multiplex Evaluation of Influenza Neutralizing Antibodies with Potential Applicability to In-Field Serological Studies,http://dx.doi.org/10.1155/2014/457932,PMC4101955,25101305,CC BY,"The increased number of outbreaks of H5 and H7 LPAI and HPAI viruses in poultry has major public and animal health implications. The continuous rapid evolution of these subtypes and the emergence of new variants influence the ability to undertake effective surveillance. Retroviral pseudotypes bearing influenza haemagglutinin (HA) and neuraminidase (NA) envelope glycoproteins represent a flexible platform for sensitive, readily standardized influenza serological assays. We describe a multiplex assay for the study of neutralizing antibodies that are directed against both influenza H5 and H7 HA. This assay permits the measurement of neutralizing antibody responses against two antigenically distinct HAs in the same serum/plasma sample thus increasing the amount and quality of serological data that can be acquired from valuable sera. Sera obtained from chickens vaccinated with a monovalent H5N2 vaccine, chickens vaccinated with a bivalent H7N1/H5N9 vaccine, or turkeys naturally infected with an H7N3 virus were evaluated in this assay and the results correlated strongly with data obtained by HI assay. We show that pseudotypes are highly stable under basic cold-chain storage conditions and following multiple rounds of freeze-thaw. We propose that this robust assay may have practical utility for in-field serosurveillance and vaccine studies in resource-limited regions worldwide.",2014 Jul 3,"['Molesti, Eleonora', 'Wright, Edward', 'Terregino, Calogero', 'Rahman, Rafat', 'Cattoli, Giovanni', 'Temperton, Nigel J.']",J Immunol Res,,,True
9e3db9f0b5e4e5811a8b21576cb08297043ddb84,PMC,Antagonizing Interferon-Mediated Immune Response by Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1155/2014/315470,PMC4101967,25101271,CC BY,"Interferons (IFNs) are important components in innate immunity involved in the first line of defense to protect host against viral infection. Porcine reproductive and respiratory syndrome virus (PRRSV) leads to severe economic losses for swine industry since being first identified in early 1990s. PRRSV interplays with host IFN production and IFN-activated signaling, which may contribute to the delayed onset and low level of neutralizing antibodies, as well as weak cell-mediated immune response in infected pigs. PRRSV encodes several proteins that act as antagonists for the IFN signaling. In this review, we summarized the various strategies used by PRRSV to antagonize IFN production and thwart IFN-activated antiviral signaling, as well as the variable interference with IFN-mediated immune response by different PRRSV strains. Thorough understanding of the interaction between PRRSV and host innate immune response will facilitate elucidation of PRRSV pathogenesis and development of a better strategy to control PRRS.",2014 Jul 3,"['Wang, Rong', 'Zhang, Yan-Jin']",Biomed Res Int,,,True
fe2c4dd2b0a96acbdcd6566d94bf227c497995ef,PMC,"Fever Screening and Detection of Febrile Arrivals at an International Airport in Korea: Association among Self-reported Fever, Infrared Thermal Camera Scanning, and Tympanic Temperature",http://dx.doi.org/10.4178/epih/e2014004,PMC4101989,25045577,CC BY,"OBJECTIVES: The purpose of this research was to measure fever prevalence and the effectiveness of a fever screening procedure in detecting febrile arrivals at an international airport in Korea. METHODS: Data were retrieved from arrivals’ health declaration forms and questionnaires for febrile arrivals at an international airport collected by a national quarantine station during the year 2012. Self-reported health declaration forms were returned by 355,887 arrivals (61% of the total arrivals). Of these, 608 symptomatic arrivals (0.2%) including 6 febrile arrivals were analyzed. RESULTS: Fever prevalence at an international airport in Korea was 0.002%. Self-reported fever was significantly positively associated with tympanic temperature (p<0.001). The difference between the thermal camera temperature (36.83°C) and tympanic (or ear) temperature (38.14°C) was not statistically significant. CONCLUSIONS: The findings imply that a procedure for mass detection of fever such as self-reported questionnaires and thermal camera scanning may serve as an effective tool for detecting febrile arrivals at quarantine stations. Future research can benefit from looking at the sensitivity, specificity, positive predictive value, and negative predictive value of the entry screening system.",2014 May 30,"['Cho, Kyung Sook', 'Yoon, Jangho']",Epidemiol Health,,,True
dda497d889e111005663783d8ac3c1289e4a7f42,PMC,Quantifying the risk of respiratory infection in healthcare workers performing high-risk procedures,http://dx.doi.org/10.1017/S095026881300304X,PMC4102100,24308554,CC BY,"This study determined the risk of respiratory infection associated with high-risk procedures (HRPs) performed by healthcare workers (HCWs) in high-risk settings. We prospectively studied 481 hospital HCWs in China, documented risk factors for infection, including performing HRPs, measured new infections, and analysed whether HRPs predicted infection. Infection outcomes were clinical respiratory infection (CRI), laboratory-confirmed viral or bacterial infection, and an influenza infection. About 12% (56/481) of the study participants performed at least one HRP, the most common being airway suctioning (7·7%, 37/481). HCWs who performed a HRP were at significantly higher risk of developing CRI and laboratory-confirmed infection [adjusted relative risk 2·9, 95% confidence interval (CI) 1·42–5·87 and 2·9, 95% CI 1·37–6·22, respectively]. Performing a HRP resulted in a threefold increase in the risk of respiratory infections. This is the first time the risk has been prospectively quantified in HCWs, providing data to inform occupational health and safety policies.",2014 Sep 5,"['MACINTYRE, C. R.', 'SEALE, H.', 'YANG, P.', 'ZHANG, Y.', 'SHI, W.', 'ALMATROUDI, A.', 'MOA, A.', 'WANG, X.', 'LI, X.', 'PANG, X.', 'WANG, Q.']",Epidemiol Infect,,,True
015c335c8cb9e5eabb352e81c0f38bf6f781b202,PMC,Validation of three geolocation strategies for health-facility attendees for research and public health surveillance in a rural setting in western Kenya,http://dx.doi.org/10.1017/S0950268814000946,PMC4102101,24787145,CC BY,"Understanding the spatial distribution of disease is critical for effective disease control. Where formal address networks do not exist, tracking spatial patterns of clinical disease is difficult. Geolocation strategies were tested at rural health facilities in western Kenya. Methods included geocoding residence by head of compound, participatory mapping and recording the self-reported nearest landmark. Geocoding was able to locate 72·9% [95% confidence interval (CI) 67·7–77·6] of individuals to within 250 m of the true compound location. The participatory mapping exercise was able to correctly locate 82·0% of compounds (95% CI 78·9–84·8) to a 2 × 2·5 km area with a 500 m buffer. The self-reported nearest landmark was able to locate 78·1% (95% CI 73·8–82·1) of compounds to the correct catchment area. These strategies tested provide options for quickly obtaining spatial information on individuals presenting at health facilities.",2014 Sep 1,"['STRESMAN, G. H.', 'STEVENSON, J. C.', 'OWAGA, C.', 'MARUBE, E.', 'ANYANGO, C.', 'DRAKELEY, C.', 'BOUSEMA, T.', 'COX, J.']",Epidemiol Infect,,,True
dcf73eb12e0e246c75505f6723e6c10608963297,PMC,Synergistic Up-Regulation of CXCL10 by Virus and IFN γ in Human Airway Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0100978,PMC4102466,25033426,CC BY,"Airway epithelial cells are the first line of defense against viral infections and are instrumental in coordinating the inflammatory response. In this study, we demonstrate the synergistic stimulation of CXCL10 mRNA and protein, a key chemokine responsible for the early immune response to viral infection, following treatment of airway epithelial cells with IFN γ and influenza virus. The synergism also occurred when the cells were treated with IFN γ and a viral replication mimicker (dsRNA) both in vitro and in vivo. Despite the requirement of type I interferon (IFNAR) signaling in dsRNA-induced CXCL10, the synergism was independent of the IFNAR pathway since it wasn’t affected by the addition of a neutralizing IFNAR antibody or the complete lack of IFNAR expression. Furthermore, the same synergistic effect was also observed when a CXCL10 promoter reporter was examined. Although the responsive promoter region contains both ISRE and NFκB sites, western blot analysis indicated that the combined treatment of IFN γ and dsRNA significantly augmented NFκB but not STAT1 activation as compared to the single treatment. Therefore, we conclude that IFN γ and dsRNA act in concert to potentiate CXCL10 expression in airway epithelial cells via an NFκB-dependent but IFNAR-STAT independent pathway and it is at least partly regulated at the transcriptional level.",2014 Jul 17,"['Oslund, Karen L.', 'Zhou, Xu', 'Lee, Boram', 'Zhu, Lingxiang', 'Duong, Trang', 'Shih, Robert', 'Baumgarth, Nicole', 'Hung, Li-Yin', 'Wu, Reen', 'Chen, Yin']",PLoS One,,,True
4a17cedf8c94b518c91dfa6719832894b5dd0417,PMC,Excessive production and extreme editing of human metapneumovirus defective interfering RNA is associated with type I IFN induction,http://dx.doi.org/10.1099/vir.0.066100-0,PMC4103063,24760760,CC BY,"Type I IFN production is one of the hallmarks of host innate immune responses upon virus infection. Whilst most respiratory viruses carry IFN antagonists, reports on human metapneumovirus (HMPV) have been conflicting. Using deep sequencing, we have demonstrated that HMPV particles accumulate excessive amounts of defective interfering RNA (DIs) rapidly upon in vitro passage, and that these are associated with IFN induction. Importantly, the DIs were edited extensively; up to 70 % of the original A and T residues had mutated to G or C, respectively. Such high editing rates of viral RNA have not, to our knowledge, been reported before. Bioinformatics and PCR assays indicated that adenosine deaminase acting on RNA (ADAR) was the most likely editing enzyme. HMPV thus has an unusually high propensity to generate DIs, which are edited at an unprecedented high frequency. The conflicting published data on HMPV IFN induction and antagonism are probably explained by DIs in virus stocks. The interaction of HMPV DIs with the RNA-editing machinery and IFN responses warrants further investigation.",2014 Aug,"['van den Hoogen, Bernadette G.', 'van Boheemen, Sander', 'de Rijck, Jonneke', 'van Nieuwkoop, Stefan', 'Smith, Derek J.', 'Laksono, Brigitta', 'Gultyaev, Alexander', 'Osterhaus, Albert D. M. E.', 'Fouchier, Ron A. M.']",J Gen Virol,,,True
412e5e7d7abb90b1bbd1e91d1c89b937987e376e,PMC,Dynamically-Driven Enhancement of the Catalytic Machinery of the SARS 3C-Like Protease by the S284-T285-I286/A Mutations on the Extra Domain,http://dx.doi.org/10.1371/journal.pone.0101941,PMC4103764,25036652,CC BY,"Previously we revealed that the extra domain of SARS 3CLpro mediated the catalysis via different mechanisms. While the R298A mutation completely abolished the dimerization, thus resulting in the inactive catalytic machinery, N214A inactivated the enzyme by altering its dynamics without significantly perturbing its structure. Here we studied another mutant with S284-T285-I286 replaced by Ala (STI/A) with a 3.6-fold activity increase and slightly enhanced dimerization. We determined its crystal structure, which still adopts the dimeric structure almost identical to that of the wild-type (WT), except for slightly tighter packing between two extra-domains. We then conducted 100-ns molecular dynamics (MD) simulations for both STI/A and WT, the longest reported so far for 3CLpro. In the simulations, two STI/A extra domains become further tightly packed, leading to a significant volume reduction of the nano-channel formed by residues from both catalytic and extra domains. The enhanced packing appears to slightly increase the dynamic stability of the N-finger and the first helix residues, which subsequently triggers the redistribution of dynamics over residues directly contacting them. This ultimately enhances the dynamical stability of the residues constituting the catalytic dyad and substrate-binding pockets. Further correlation analysis reveals that a global network of the correlated motions exists in the protease, whose components include all residues identified so far to be critical for the dimerization and catalysis. Most strikingly, the N214A mutation globally decouples this network while the STI/A mutation alters the correlation pattern. Together with previous results, the present study establishes that besides the classic structural allostery, the dynamic allostery also operates in the SARS 3CLpro, which is surprisingly able to relay the perturbations on the extra domain onto the catalytic machinery to manifest opposite catalytic effects. Our results thus imply a promising avenue to design specific inhibitors for 3CL proteases by disrupting their dynamic correlation network.",2014 Jul 18,"['Lim, Liangzhong', 'Shi, Jiahai', 'Mu, Yuguang', 'Song, Jianxing']",PLoS One,,,True
dba0cdf3fbecdba11207ba0d7da322fc2a83b798,PMC,Building core capacities at the designated points of entry according to the International Health Regulations 2005: a review of the progress and prospects in Taiwan,http://dx.doi.org/10.3402/gha.v7.24516,PMC4104008,25037903,CC BY,"BACKGROUND: As designated points of entry (PoEs) play a critical role in preventing the transmission of international public health risks, huge efforts have been invested in Taiwan to improve the core capacities specified in the International Health Regulations 2005 (IHR 2005). This article reviews how Taiwan strengthened the core capacities at the Taoyuan International Airport (TIA) and the Port of Kaohsiung (PoK) by applying a new, practicable model. DESIGN: An IHR PoE program was initiated for implementing the IHR core capacities at designated PoEs. The main methods of this program were 1) identifying the designated PoEs according to the pre-determined criteria, 2) identifying the competent authority for each health measure, 3) building a close collaborative relationship between stakeholders from the central and PoE level, 4) designing three stages of systematic assessment using the assessment tool published by the World Health Organization (WHO), and 5) undertaking action plans targeting the gaps identified by the assessments. RESULTS: Results of the self-assessment, preliminary external assessment, and follow-up external assessment revealed a continuous progressive trend at the TIA (86, 91, and 100%, respectively), and at the PoK (77, 97, and 99.9%, respectively). The results of the follow-up external assessment indicated that both these designated PoEs already conformed to the IHR requirements. These achievements were highly associated with strong collaboration, continuous empowerment, efficient resource integration, and sustained commitments. CONCLUSIONS: Considering that many countries had requested for an extension on the deadline to fulfill the IHR 2005 core capacity requirements, Taiwan's experiences can be a source of learning for countries striving to fully implement these requirements. Further, in order to broaden the scope of public health protection into promoting global security, Taiwan will keep its commitments on multisectoral cooperation, human resource capacity building, and maintaining routine and emergency capacities.",2014 Jul 17,"['Chiu, Hsiao-Hsuan', 'Hsieh, Jui-Wei', 'Wu, Yi-Chun', 'Chou, Jih-Haw', 'Chang, Feng-Yee']",Glob Health Action,,,True
3c43e9e66c5b384ac03f0067bc8d16a9efdd5fb9,PMC,Choindroitinase ABC I-Mediated Enhancement of Oncolytic Virus Spread and Anti Tumor Efficacy: A Mathematical Model,http://dx.doi.org/10.1371/journal.pone.0102499,PMC4105445,25047810,CC BY,"Oncolytic viruses are genetically engineered viruses that are designed to kill cancer cells while doing minimal damage to normal healthy tissue. After being injected into a tumor, they infect cancer cells, multiply inside them, and when a cancer cell is killed they move on to spread and infect other cancer cells. Chondroitinase ABC (Chase-ABC) is a bacterial enzyme that can remove a major glioma ECM component, chondroitin sulfate glycosoamino glycans from proteoglycans without any deleterious effects in vivo. It has been shown that Chase-ABC treatment is able to promote the spread of the viruses, increasing the efficacy of the viral treatment. In this paper we develop a mathematical model to investigate the effect of the Chase-ABC on the treatment of glioma by oncolytic viruses (OV). We show that the model's predictions agree with experimental results for a spherical glioma. We then use the model to test various treatment options in the heterogeneous microenvironment of the brain. The model predicts that separate injections of OV, one into the center of the tumor and another outside the tumor will result in better outcome than if the total injection is outside the tumor. In particular, the injection of the ECM-degrading enzyme (Chase-ABC) on the periphery of the main tumor core need to be administered in an optimal strategy in order to infect and eradicate the infiltrating glioma cells outside the tumor core in addition to proliferative cells in the bulk of tumor core. The model also predicts that the size of tumor satellites and distance between the primary tumor and multifocal/satellite lesions may be an important factor for the efficacy of the viral therapy with Chase treatment.",2014 Jul 21,"['Kim, Yangjin', 'Lee, Hyun Geun', 'Dmitrieva, Nina', 'Kim, Junseok', 'Kaur, Balveen', 'Friedman, Avner']",PLoS One,,,True
8dcc9848e421e45ac829203e4e6fe58e6ac130e5,PMC,Choindroitinase ABC I-Mediated Enhancement of Oncolytic Virus Spread and Anti Tumor Efficacy: A Mathematical Model,http://dx.doi.org/10.1371/journal.pone.0102499,PMC4105445,25047810,CC BY,"Oncolytic viruses are genetically engineered viruses that are designed to kill cancer cells while doing minimal damage to normal healthy tissue. After being injected into a tumor, they infect cancer cells, multiply inside them, and when a cancer cell is killed they move on to spread and infect other cancer cells. Chondroitinase ABC (Chase-ABC) is a bacterial enzyme that can remove a major glioma ECM component, chondroitin sulfate glycosoamino glycans from proteoglycans without any deleterious effects in vivo. It has been shown that Chase-ABC treatment is able to promote the spread of the viruses, increasing the efficacy of the viral treatment. In this paper we develop a mathematical model to investigate the effect of the Chase-ABC on the treatment of glioma by oncolytic viruses (OV). We show that the model's predictions agree with experimental results for a spherical glioma. We then use the model to test various treatment options in the heterogeneous microenvironment of the brain. The model predicts that separate injections of OV, one into the center of the tumor and another outside the tumor will result in better outcome than if the total injection is outside the tumor. In particular, the injection of the ECM-degrading enzyme (Chase-ABC) on the periphery of the main tumor core need to be administered in an optimal strategy in order to infect and eradicate the infiltrating glioma cells outside the tumor core in addition to proliferative cells in the bulk of tumor core. The model also predicts that the size of tumor satellites and distance between the primary tumor and multifocal/satellite lesions may be an important factor for the efficacy of the viral therapy with Chase treatment.",2014 Jul 21,"['Kim, Yangjin', 'Lee, Hyun Geun', 'Dmitrieva, Nina', 'Kim, Junseok', 'Kaur, Balveen', 'Friedman, Avner']",PLoS One,,,True
9eff33e415aeff95305afd9a4914f15b1eafab84,PMC,"Viral etiology and seasonality of influenza-like illness in Gabon, March 2010 to June 2011",http://dx.doi.org/10.1186/1471-2334-14-373,PMC4107952,25000832,CC BY,"BACKGROUND: Surveillance of influenza-like illness (ILI) in Central Africa began only recently, and few data are therefore available on the circulation of influenza virus and other respiratory viruses. In Gabon, a Central African country, we established a surveillance network in four major towns in order to analyze cases of ILI among patients who visited health centers between March 2010 and June 2011, and to determine the viral etiology. METHODS: Nasal swabs were sent for analysis to the Centre International de Recherches Médicales de Franceville, where they were screened for 17 respiratory viruses in a multiplex real-time reverse transcription polymerase chain reaction for all pathogens according the following pairs: adenovirus/parainfluenza virus 4, respiratory syncytial virus/human metapneumovirus, parainfluenza virus 1/parainfluenza virus 2, pandemic influenza virus A/seasonal influenza virus A (H1N1, H3N2)/seasonal influenza virus B, human coronaviruses 229E/OC43, human coronaviruses NL63/HKU1, rhinovirus/human parechovirus, and enterovirus/parainfluenza virus 3. RESULTS: We analyzed a total of 1041 specimens, of which 639 (61%) were positive for at least one virus. Three-quarters of the patients were children under five years old. We therefore focused on this age group, in which 68.1% of patients were positive for at least one virus. The most common viruses were adenoviruses (17.5%), followed by parainfluenza viruses (PIVs) 1–4 (16.8%), enteroviruses (EV) (14.7%), respiratory syncytial virus (RSV) (13.5%), and influenza virus (11.9%). The prevalence of some viruses was subject to geographic and seasonal variations. One-third of positive samples contained more than one virus. CONCLUSIONS: Like most studies in the world, the virus PIVs, EV, RSV, Influenza virus, HRV were predominant among children under five years old in Gabon. An exception is made for adenoviruses which have a high prevalence in our study. However adenoviruses can be detected in asymptomatic persons. These finding gave a better knowledge of the circulation and the seasonality of the viruses involved in ILI in Gabon.",2014 Jul 7,"['Lekana-Douki, Sonia Etenna', 'Nkoghe, Dieudonné', 'Drosten, Christian', 'Ngoungou, Edgar Brice', 'Drexler, Jan Felix', 'Leroy, Eric M']",BMC Infect Dis,,,True
22371f1a9a91782adf48ffc5ad7d54d9a7a61b13,PMC,Q fever in the Netherlands: public perceptions and behavioral responses in three different epidemiological regions: a follow-up study,http://dx.doi.org/10.1186/1471-2458-14-263,PMC4108011,24645896,CC BY,"BACKGROUND: Over the past years, Q fever has become a major public health problem in the Netherlands, with a peak of 2,357 human cases in 2009. In the first instance, Q fever was mainly a local problem of one province with a high density of large dairy goat farms, but in 2009 an alarming increase of Q fever cases was observed in adjacent provinces. The aim of this study was to identify trends over time and regional differences in public perceptions and behaviors, as well as predictors of preventive behavior regarding Q fever. METHODS: One cross-sectional survey (2009) and two follow-up surveys (2010, 2012) were performed. Adults, aged ≥18 years, that participated in a representative internet panel were invited (survey 1, n = 1347; survey 2, n = 1249; survey 3, n = 1030). RESULTS: Overall, public perceptions and behaviors regarding Q fever were consistent with the trends over time in the numbers of new human Q fever cases in different epidemiological regions and the amount of media attention focused on Q fever in the Netherlands. However, there were remarkably low levels of perceived vulnerability and perceived anxiety, particularly in the region of highest incidence, where three-quarters of the total cases occurred in 2009. Predictors of preventive behavior were being female, older aged, having Q fever themselves or someone in their household, more knowledge, and higher levels of perceived severity, anxiety and (self-) efficacy. CONCLUSIONS: During future outbreaks of (zoonotic) infectious diseases, it will be important to instil a realistic sense of vulnerability by providing the public with accurate information on the risk of becoming infected. This should be given in addition to information about the severity of the disease, the efficacy of measures, and instructions for minimising infection risk with appropriate, feasible preventative measures. Furthermore, public information should be adapted to regional circumstances.",2014 Mar 20,"['Bults, Marloes', 'Beaujean, Desirée', 'Wijkmans, Clementine', 'Richardus, Jan Hendrik', 'Voeten, Hélène']",BMC Public Health,,,True
938354ea93017c47a439518c4d67178f63e70088,PMC,Recent advances in live cell imaging of hepatoma cells,http://dx.doi.org/10.1186/1471-2121-15-26,PMC4108253,25005127,CC BY,"Live cell imaging enables the study of dynamic processes of living cells in real time by use of suitable reporter proteins and the staining of specific cellular structures and/or organelles. With the availability of advanced optical devices and improved cell culture protocols it has become a rapidly growing research methodology. The success of this technique relies mainly on the selection of suitable reporter proteins, construction of recombinant plasmids possessing cell type specific promoters as well as reliable methods of gene transfer. This review aims to provide an overview of the recent developments in the field of marker proteins (bioluminescence and fluorescent) and methodologies (fluorescent resonance energy transfer, fluorescent recovery after photobleaching and proximity ligation assay) employed as to achieve an improved imaging of biological processes in hepatoma cells. Moreover, different expression systems of marker proteins and the modes of gene transfer are discussed with emphasis on the study of lipid droplet formation in hepatocytes as an example.",2014 Jul 8,"['Salipalli, Sandeep', 'Singh, Prafull Kumar', 'Borlak, Jürgen']",BMC Cell Biol,,,True
a795b134187db133ca06a515ab1bec787916af2d,PMC,"SELDI-TOF-MS Proteomic Profiling of Serum, Urine, and Amniotic Fluid in Neural Tube Defects",http://dx.doi.org/10.1371/journal.pone.0103276,PMC4108413,25054433,CC BY,"Neural tube defects (NTDs) are common birth defects, whose specific biomarkers are needed. The purpose of this pilot study is to determine whether protein profiling in NTD-mothers differ from normal controls using SELDI-TOF-MS. ProteinChip Biomarker System was used to evaluate 82 maternal serum samples, 78 urine samples and 76 amniotic fluid samples. The validity of classification tree was then challenged with a blind test set including another 20 NTD-mothers and 18 controls in serum samples, and another 19 NTD-mothers and 17 controls in urine samples, and another 20 NTD-mothers and 17 controls in amniotic fluid samples. Eight proteins detected in serum samples were up-regulated and four proteins were down-regulated in the NTD group. Four proteins detected in urine samples were up-regulated and one protein was down-regulated in the NTD group. Six proteins detected in amniotic fluid samples were up-regulated and one protein was down-regulated in the NTD group. The classification tree for serum samples separated NTDs from healthy individuals, achieving a sensitivity of 91% and a specificity of 97% in the training set, and achieving a sensitivity of 90% and a specificity of 97% and a positive predictive value of 95% in the test set. The classification tree for urine samples separated NTDs from controls, achieving a sensitivity of 95% and a specificity of 94% in the training set, and achieving a sensitivity of 89% and a specificity of 82% and a positive predictive value of 85% in the test set. The classification tree for amniotic fluid samples separated NTDs from controls, achieving a sensitivity of 93% and a specificity of 89% in the training set, and achieving a sensitivity of 90% and a specificity of 88% and a positive predictive value of 90% in the test set. These suggest that SELDI-TOF-MS is an additional method for NTDs pregnancies detection.",2014 Jul 23,"['Liu, Zhenjiang', 'Yuan, Zhengwei', 'Zhao, Qun']",PLoS One,,,True
3aa75376556fa96324ad4cacb0b862ad86b7a11e,PMC,A Novel MVA Vectored Chikungunya Virus Vaccine Elicits Protective Immunity in Mice,http://dx.doi.org/10.1371/journal.pntd.0002970,PMC4109897,25058320,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a re-emerging arbovirus associated with febrile illness often accompanied by rash and arthralgia that may persist for several years. Outbreaks are associated with high morbidity and create a public health challenge for countries affected. Recent outbreaks have occurred in both Europe and the Americas, suggesting CHIKV may continue to spread. Despite the sustained threat of the virus, there is no approved vaccine or antiviral therapy against CHIKV. Therefore, it is critical to develop a vaccine that is both well tolerated and highly protective. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we describe the construction and characterization of a modified Vaccinia virus Ankara (MVA) virus expressing CHIKV E3 and E2 proteins (MVA-CHIK) that protected several mouse models from challenge with CHIKV. In particular, BALB/c mice were completely protected against viremia upon challenge with CHIKV after two doses of MVA-CHIK. Additionally, A129 mice (deficient in IFNα/β) were protected from viremia, footpad swelling, and mortality. While high anti-virus antibodies were elicited, low or undetectable levels of neutralizing antibodies were produced in both mouse models. However, passive transfer of MVA-CHIK immune serum to naïve mice did not protect against mortality, suggesting that antibodies may not be the main effectors of protection afforded by MVA-CHIK. Furthermore, depletion of CD4(+), but not CD8(+) T-cells from vaccinated mice resulted in 100% mortality, implicating the indispensable role of CD4(+) T-cells in the protection afforded by MVA-CHIK. CONCLUSIONS/SIGNIFICANCE: The results presented herein demonstrate the potential of MVA to effectively express CHIKV E3-E2 proteins and generate protective immune responses. Our findings challenge the assumption that only neutralizing antibodies are effective in providing protection against CHIKV, and provides a framework for the development of novel, more effective vaccine strategies to combat CHIKV.",2014 Jul 24,"['Weger-Lucarelli, James', 'Chu, Haiyan', 'Aliota, Matthew T.', 'Partidos, Charalambos D.', 'Osorio, Jorge E.']",PLoS Negl Trop Dis,,,True
f8f2a61fb217ad9fb00b93b7ec2bbb016bcbb881,PMC,Using Informatics and the Electronic Medical Record to Describe Antimicrobial Use in the Clinical Management of Diarrhea Cases at 12 Companion Animal Practices,http://dx.doi.org/10.1371/journal.pone.0103190,PMC4109994,25057893,CC BY,"Antimicrobial drugs may be used to treat diarrheal illness in companion animals. It is important to monitor antimicrobial use to better understand trends and patterns in antimicrobial resistance. There is no monitoring of antimicrobial use in companion animals in Canada. To explore how the use of electronic medical records could contribute to the ongoing, systematic collection of antimicrobial use data in companion animals, anonymized electronic medical records were extracted from 12 participating companion animal practices and warehoused at the University of Calgary. We used the pre-diagnostic, clinical features of diarrhea as the case definition in this study. Using text-mining technologies, cases of diarrhea were described by each of the following variables: diagnostic laboratory tests performed, the etiological diagnosis and antimicrobial therapies. The ability of the text miner to accurately describe the cases for each of the variables was evaluated. It could not reliably classify cases in terms of diagnostic tests or etiological diagnosis; a manual review of a random sample of 500 diarrhea cases determined that 88/500 (17.6%) of the target cases underwent diagnostic testing of which 36/88 (40.9%) had an etiological diagnosis. Text mining, compared to a human reviewer, could accurately identify cases that had been treated with antimicrobials with high sensitivity (92%, 95% confidence interval, 88.1%–95.4%) and specificity (85%, 95% confidence interval, 80.2%–89.1%). Overall, 7400/15,928 (46.5%) of pets presenting with diarrhea were treated with antimicrobials. Some temporal trends and patterns of the antimicrobial use are described. The results from this study suggest that informatics and the electronic medical records could be useful for monitoring trends in antimicrobial use.",2014 Jul 24,"['Anholt, R. Michele', 'Berezowski, John', 'Ribble, Carl S.', 'Russell, Margaret L.', 'Stephen, Craig']",PLoS One,,,True
a35a9ab63e50b5eed8710a67b89d6c31d53cd191,PMC,Risk factors and epidemiological characteristics of new neonatal porcine diarrhoea syndrome in four Danish herds,http://dx.doi.org/10.1186/1746-6148-10-151,PMC4110237,25012922,CC BY,"BACKGROUND: The epidemiology of New Neonatal Porcine Diarrhoea Syndrome (NNPDS) was studied in four selected herds. A total of 941 new born piglets in 86 litters were evaluated for five consecutive days. NNPDS is a newly emerged syndrome, characterized by diarrhoea within the first week of life, which is un-responsive to antibiotics and not associated with known pathogens. The aetiology behind the syndrome is unknown, and specific risk factors predisposing piglets to develop NNPDS also remain to be determined. The study evaluated sow and piglet-level risk factors for developing NNPDS and described the epidemiologic characteristics within four herds previously diagnosed with the syndrome. NNPDS was defined as diarrhoea at any time-point during the second to fifth day of life. RESULTS: NNPDS was observed in a total of 60% (range: 39%-89%) of first parity piglets and 36% (range: 19-65%) of piglets born by mature sows. In total of 26% of piglets had liquid faeces on the day of birth. Approximately half of these piglets developed NNPDS. In the majority of cases (50-70% of cases within herds) symptoms started on the second or third day of life. Piglets in Herd 1 had12.8 times higher probability of developing NNPDS than piglets in Herd 4. First parity piglets had a 4.1 higher probability of developing NNPDS than piglets born by mature sows. Birth weight and faecal consistency on the day of birth were minor risk factors, each significant within one herd. CONCLUSIONS: The most important factors associated with NNPDS were herd of origin and sow-parity. The reason for one of the herds experiencing a considerably more severe outbreak than the others was not explained by factors addressed in this study. The epidemiological pattern of diarrhoea varied a lot between herds; however, in all herds first parity piglets seemed predisposed. This association may be explained by an infectious background of the syndrome, but further studies are needed to explain this association.",2014 Jul 10,"['Kongsted, Hanne', 'Toft, Nils', 'Nielsen, Jens Peter']",BMC Vet Res,,,True
42d750019224d03261c70185a1bae3afe5be8c3a,PMC,Draft Genome Sequence of the Bordetella bronchiseptica Swine Isolate KM22,http://dx.doi.org/10.1128/genomeA.00670-14,PMC4110755,25013141,CC BY,Bordetella bronchiseptica swine isolate KM22 has been used in experimental infections of swine as a model of clinical B. bronchiseptica infections within swine herds and to study host-to-host transmission. Here we report the draft genome sequence of KM22.,2014 Jul 10,"['Nicholson, Tracy L.', 'Shore, Sarah M.', 'Bayles, Darrell O.', 'Register, Karen B.', 'Kingsley, Robert A.']",Genome Announc,,,True
284a7df2b370e893122a58ce3af9a9d2daaab704,PMC,A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection,http://dx.doi.org/10.7554/eLife.02910,PMC4112549,24966209,CC0,"Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into Lepidopteran cells. This restriction is overcome when cells are co-infected with vaccinia virus (VACV), a vertebrate DNA virus. Using RNAi screening, we show that Lepidopteran RNAi, Nuclear Factor-κB, and ubiquitin-proteasome pathways restrict RNA virus infection. Surprisingly, a highly conserved, uncharacterized VACV protein, A51R, can partially overcome this virus restriction. We show that A51R is also critical for VACV replication in vertebrate cells and for pathogenesis in mice. Interestingly, A51R colocalizes with, and stabilizes, host microtubules and also associates with ubiquitin. We show that A51R promotes viral protein stability, possibly by preventing ubiquitin-dependent targeting of viral proteins for destruction. Importantly, our studies reveal exciting new opportunities to study virus-host interactions in experimentally-tractable Lepidopteran systems. DOI: http://dx.doi.org/10.7554/eLife.02910.001",2014 Jun 25,"['Gammon, Don B', 'Duraffour, Sophie', 'Rozelle, Daniel K', 'Hehnly, Heidi', 'Sharma, Rita', 'Sparks, Michael E', 'West, Cara C', 'Chen, Ying', 'Moresco, James J', 'Andrei, Graciela', 'Connor, John H', 'Conte, Darryl', 'Gundersen-Rindal, Dawn E', 'Marshall, William L', 'Yates, John R', 'Silverman, Neal', 'Mello, Craig C']",eLife,,,True
c7d60067e11331d3c5e1f9b1d79e70caacb13f25,PMC,Kawasaki disease patients homozygous for the rs12252-C variant of interferon-induced transmembrane protein-3 are significantly more likely to develop coronary artery lesions,http://dx.doi.org/10.1002/mgg3.79,PMC4113277,25077179,CC BY,,2014 Jul 14,"['Bowles, Neil E', 'Arrington, Cammon B', 'Hirono, Keiichi', 'Nakamura, Tsuneyuki', 'Ngo, Long', 'Wee, Yin Shen', 'Ichida, Fukiko', 'Weis, John H']",Mol Genet Genomic Med,,,True
7db22f7f81977109d493a0edf8ed75562648e839,PMC,Recombinant Scorpine Produced Using SUMO Fusion Partner in Escherichia coli Has the Activities against Clinically Isolated Bacteria and Inhibits the Plasmodium falciparum Parasitemia In Vitro,http://dx.doi.org/10.1371/journal.pone.0103456,PMC4113386,25068263,CC BY,"Scorpine, a small cationic peptide from the venom of Pandinus imperator, which has been shown to have anti-bacterial and anti-plasmodial activities, has potential important applications in the pharmaceutical industries. However, the isolation of scorpine from natural sources is inefficient and time-consuming. Here, we first report the expression and purification of recombinant scorpine in Escherichia coli, using small ubiquitin-related modifier (SUMO) fusion partner. The fusion protein was expressed in soluble form in E. coli, and expression was verified by SDS-PAGE and western blotting analysis. The fusion protein was purified to 90% purity by nickel–nitrilotriacetic acid (Ni(2+)–NTA) resin chromatography. After the SUMO-scorpine fusion protein was cleaved by the SUMO protease, the cleaved sample was reapplied to a Ni(2+)–NTA column. Tricine/SDS-PAGE gel results indicated that Scorpine had been purified successfully to more than 95% purity. The recombinantly expressed Scorpine showed anti-bacterial activity against two standard bacteria including Staphylococcus aureus ATCC 29213 and Acinetobacter baumannii ATCC 19606, and clinically isolated bacteria including S. aureus S, S. aureus R, A. baumannii S, and A. baumannii R. It also produced 100% reduction in Plasmodium falciparum parasitemia in vitro. Thus, the expression strategy presented in this study allowed convenient high yield and easy purification of recombinant Scorpine for pharmaceutical applications in the future.",2014 Jul 28,"['Zhang, Chao', 'He, Xinlong', 'Gu, Yaping', 'Zhou, Huayun', 'Cao, Jun', 'Gao, Qi']",PLoS One,,,True
8086b478a036f07fc6a809c63dc7d52acb659fe1,PMC,RNA Virus Reverse Genetics and Vaccine Design,http://dx.doi.org/10.3390/v6072531,PMC4113782,24967693,CC BY,"RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine development. Here, we review the impact of RNA virus reverse genetics systems on past and current efforts to design effective and safe viral therapeutics and vaccines.",2014 Jun 25,"['Stobart, Christopher C.', 'Moore, Martin L.']",Viruses,,,True
6223b84467e6bdc875ce49a403acf34055e4d141,PMC,Modified Vaccinia Virus Ankara (MVA) as Production Platform for Vaccines against Influenza and Other Viral Respiratory Diseases,http://dx.doi.org/10.3390/v6072735,PMC4113791,25036462,CC BY,"Respiratory viruses infections caused by influenza viruses, human parainfluenza virus (hPIV), respiratory syncytial virus (RSV) and coronaviruses are an eminent threat for public health. Currently, there are no licensed vaccines available for hPIV, RSV and coronaviruses, and the available seasonal influenza vaccines have considerable limitations. With regard to pandemic preparedness, it is important that procedures are in place to respond rapidly and produce tailor made vaccines against these respiratory viruses on short notice. Moreover, especially for influenza there is great need for the development of a universal vaccine that induces broad protective immunity against influenza viruses of various subtypes. Modified Vaccinia Virus Ankara (MVA) is a replication-deficient viral vector that holds great promise as a vaccine platform. MVA can encode one or more foreign antigens and thus functions as a multivalent vaccine. The vector can be used at biosafety level 1, has intrinsic adjuvant capacities and induces humoral and cellular immune responses. However, there are some practical and regulatory issues that need to be addressed in order to develop MVA-based vaccines on short notice at the verge of a pandemic. In this review, we discuss promising novel influenza virus vaccine targets and the use of MVA for vaccine development against various respiratory viruses.",2014 Jul 17,"['Altenburg, Arwen F.', 'Kreijtz, Joost H. C. M.', 'de Vries, Rory D.', 'Song, Fei', 'Fux, Robert', 'Rimmelzwaan, Guus F.', 'Sutter, Gerd', 'Volz, Asisa']",Viruses,,,True
b8aeb68acc940bb4f4d68bb6e7bb89da81c5d12f,PMC,Membranous Replication Factories Induced by Plus-Strand RNA Viruses,http://dx.doi.org/10.3390/v6072826,PMC4113795,25054883,CC BY,"In this review, we summarize the current knowledge about the membranous replication factories of members of plus-strand (+) RNA viruses. We discuss primarily the architecture of these complex membrane rearrangements, because this topic emerged in the last few years as electron tomography has become more widely available. A general denominator is that two “morphotypes” of membrane alterations can be found that are exemplified by flaviviruses and hepaciviruses: membrane invaginations towards the lumen of the endoplasmatic reticulum (ER) and double membrane vesicles, representing extrusions also originating from the ER, respectively. We hypothesize that either morphotype might reflect common pathways and principles that are used by these viruses to form their membranous replication compartments.",2014 Jul 22,"['Romero-Brey, Inés', 'Bartenschlager, Ralf']",Viruses,,,True
bd392572caeafc342bc6b6c54ad637bb8c2dfe4b,PMC,Usage of Social Media and Smartphone Application in Assessment of Physical and Psychological Well-Being of Individuals in Times of a Major Air Pollution Crisis,http://dx.doi.org/10.2196/mhealth.2827,PMC4114481,25098255,CC BY,"BACKGROUND: Crisis situations bring about many challenges to researchers, public institutions, and governments in collecting data and conducting research in affected individuals. Recent developments in Web-based and smartphone technologies have offered government and nongovernment organizations a new system to disseminate and acquire information. However, research into this area is still lacking. The current study focuses largely on how new social networking websites and, in particular, smartphone technologies could have helped in the acquisition of crucial research data from the general population during the recent 2013 Southeast Asian Haze. This crisis lasted only for 1 week, and is unlike other crisis where there are large-scale consequential after-effects. OBJECTIVE: To determine whether respondents will make use of Internet, social media, and smartphone technologies to provide feedback regarding their physical and psychological wellbeing during a crisis, and if so, will these new mechanisms be as effective as conventional, technological, Internet-based website technologies. METHODS: A Web-based database and a smartphone application were developed. Participants were recruited by snowball sampling. The participants were recruited either via a self-sponsored Facebook post featuring a direct link to the questionnaire on physical and psychological wellbeing and also a smartphone Web-based application; or via dissemination of the questionnaire link by emails, directed to the same group of participants. Information pertaining to physical and psychological wellbeing was collated. RESULTS: A total of 298 respondents took part in the survey. Most of them were between the ages of 20 to 29 years and had a university education. More individuals preferred the option of accessing and providing feedback to a survey on physical and psychological wellbeing via direct access to a Web-based questionnaire. Statistical analysis showed that demographic variables like age, gender, and educational levels did not influence the mechanism of access. In addition, the participants reported a mean number of 4.03 physical symptoms (SD 2.6). The total Impact of Event Scale–Revised (IES-R) score was 18.47 (SD 11.69), which indicated that the study population did experience psychological stress but not post-traumatic stress disorder. The perceived dangerous Pollutant Standards Index (PSI) level and the number of physical symptoms were associated with higher IES-R Score (P<.05). CONCLUSIONS: This is one of the first few studies demonstrating the use of Internet in data collection during an air-pollution crisis. Our results demonstrated that the newer technological modalities have the potential to acquire data, similar to that of conventional technologies. Demographic variables did not influence the mechanism of usage. In addition, our findings also suggested that there are acute physical and psychological impacts on the population from an air-pollution crisis.",2014 Mar 25,"['Zhang, Melvyn WB', 'Ho, Cyrus SH', 'Fang, Pan', 'Lu, Yanxia', 'Ho, Roger CM']",JMIR Mhealth Uhealth,,,False
6424a93c7b3cafd9bbe5c14bfc35940c81f9333e,PMC,Usage of Social Media and Smartphone Application in Assessment of Physical and Psychological Well-Being of Individuals in Times of a Major Air Pollution Crisis,http://dx.doi.org/10.2196/mhealth.2827,PMC4114481,25098255,CC BY,"BACKGROUND: Crisis situations bring about many challenges to researchers, public institutions, and governments in collecting data and conducting research in affected individuals. Recent developments in Web-based and smartphone technologies have offered government and nongovernment organizations a new system to disseminate and acquire information. However, research into this area is still lacking. The current study focuses largely on how new social networking websites and, in particular, smartphone technologies could have helped in the acquisition of crucial research data from the general population during the recent 2013 Southeast Asian Haze. This crisis lasted only for 1 week, and is unlike other crisis where there are large-scale consequential after-effects. OBJECTIVE: To determine whether respondents will make use of Internet, social media, and smartphone technologies to provide feedback regarding their physical and psychological wellbeing during a crisis, and if so, will these new mechanisms be as effective as conventional, technological, Internet-based website technologies. METHODS: A Web-based database and a smartphone application were developed. Participants were recruited by snowball sampling. The participants were recruited either via a self-sponsored Facebook post featuring a direct link to the questionnaire on physical and psychological wellbeing and also a smartphone Web-based application; or via dissemination of the questionnaire link by emails, directed to the same group of participants. Information pertaining to physical and psychological wellbeing was collated. RESULTS: A total of 298 respondents took part in the survey. Most of them were between the ages of 20 to 29 years and had a university education. More individuals preferred the option of accessing and providing feedback to a survey on physical and psychological wellbeing via direct access to a Web-based questionnaire. Statistical analysis showed that demographic variables like age, gender, and educational levels did not influence the mechanism of access. In addition, the participants reported a mean number of 4.03 physical symptoms (SD 2.6). The total Impact of Event Scale–Revised (IES-R) score was 18.47 (SD 11.69), which indicated that the study population did experience psychological stress but not post-traumatic stress disorder. The perceived dangerous Pollutant Standards Index (PSI) level and the number of physical symptoms were associated with higher IES-R Score (P<.05). CONCLUSIONS: This is one of the first few studies demonstrating the use of Internet in data collection during an air-pollution crisis. Our results demonstrated that the newer technological modalities have the potential to acquire data, similar to that of conventional technologies. Demographic variables did not influence the mechanism of usage. In addition, our findings also suggested that there are acute physical and psychological impacts on the population from an air-pollution crisis.",2014 Mar 25,"['Zhang, Melvyn WB', 'Ho, Cyrus SH', 'Fang, Pan', 'Lu, Yanxia', 'Ho, Roger CM']",JMIR Mhealth Uhealth,,,False
a445e4cc0146046d191344e3b61cd8dd4f33eb83,PMC,Human Coronaviruses Associated with Upper Respiratory Tract Infections in Three Rural Areas of Ghana,http://dx.doi.org/10.1371/journal.pone.0099782,PMC4117488,25080241,CC BY,"BACKGROUND: Acute respiratory tract infections (ARI) are the leading cause of morbidity and mortality in developing countries, especially in Africa. This study sought to determine whether human coronaviruses (HCoVs) are associated with upper respiratory tract infections among older children and adults in Ghana. METHODS: We conducted a case control study among older children and adults in three rural areas of Ghana using asymptomatic subjects as controls. Nasal/Nasopharyngeal swabs were tested for Middle East respiratory syndrome coronavirus (MERS-CoV), HCoV-22E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 using Reverse Transcriptase Real-Time Polymerase Chain Reaction. RESULTS: Out of 1,213 subjects recruited, 150 (12.4%) were positive for one or more viruses. Of these, single virus detections occurred in 146 subjects (12.0%) and multiple detections occurred in 4 (0.3%). Compared with control subjects, infections with HCoV-229E (OR = 5.15, 95%CI = 2.24–11.78), HCoV-OC43 (OR = 6.16, 95%CI = 1.77–21.65) and combine HCoVs (OR = 2.36, 95%CI = 1.5 = 3.72) were associated with upper respiratory tract infections. HCoVs were found to be seasonally dependent with significant detections in the harmattan season (mainly HCoV-229E) and wet season (mainly HCoV-NL63). A comparison of the obtained sequences resulted in no differences to sequences already published in GenBank. CONCLUSION: HCoVs could play significant role in causing upper respiratory tract infections among adults and older children in rural areas of Ghana.",2014 Jul 31,"['Owusu, Michael', 'Annan, Augustina', 'Corman, Victor Max', 'Larbi, Richard', 'Anti, Priscilla', 'Drexler, Jan Felix', 'Agbenyega, Olivia', 'Adu-Sarkodie, Yaw', 'Drosten, Christian']",PLoS One,,,True
c83a4991d36a6086da50b13968955329c5f07a6c,PMC,Inflammatory response in mixed viral-bacterial community-acquired pneumonia,http://dx.doi.org/10.1186/1471-2466-14-123,PMC4118651,25073709,CC BY,"BACKGROUND: The role of mixed pneumonia (virus + bacteria) in community-acquired pneumonia (CAP) has been described in recent years. However, it is not known whether the systemic inflammatory profile is different compared to monomicrobial CAP. We wanted to investigate this profile of mixed viral-bacterial infection and to compare it to monomicrobial bacterial or viral CAP. METHODS: We measured baseline serum procalcitonin (PCT), C reactive protein (CRP), and white blood cell (WBC) count in 171 patients with CAP with definite etiology admitted to a tertiary hospital: 59 (34.5%) bacterial, 66 (39.%) viral and 46 (27%) mixed (viral-bacterial). RESULTS: Serum PCT levels were higher in mixed and bacterial CAP compared to viral CAP. CRP levels were higher in mixed CAP compared to the other groups. CRP was independently associated with mixed CAP. CRP levels below 26 mg/dL were indicative of an etiology other than mixed in 83% of cases, but the positive predictive value was 45%. PCT levels over 2.10 ng/mL had a positive predictive value for bacterial-involved CAP versus viral CAP of 78%, but the negative predictive value was 48%. CONCLUSIONS: Mixed CAP has a different inflammatory pattern compared to bacterial or viral CAP. High CRP levels may be useful for clinicians to suspect mixed CAP.",2014 Jul 29,"['Bello, Salvador', 'Mincholé, Elisa', 'Fandos, Sergio', 'Lasierra, Ana B', 'Ruiz, María A', 'Simon, Ana L', 'Panadero, Carolina', 'Lapresta, Carlos', 'Menendez, Rosario', 'Torres, Antoni']",BMC Pulm Med,,,True
ed02cdbaaf52f191ad3bebb5a3bc117524718c8e,PMC,Establishment and Clinical Applications of a Portable System for Capturing Influenza Viruses Released through Coughing,http://dx.doi.org/10.1371/journal.pone.0103560,PMC4118893,25083787,CC BY,"Coughing plays an important role in influenza transmission; however, there is insufficient information regarding the viral load in cough because of the lack of convenient and reliable collection methods. We developed a portable airborne particle-collection system to measure the viral load; it is equipped with an air sampler to draw air and pass it through a gelatin membrane filter connected to a cone-shaped, megaphone-like device to guide the cough airflow to the membrane. The membrane was dissolved in a medium, and the viral load was measured using quantitative real-time reverse transcriptase-polymerase chain reaction and a plaque assay. The approximate viral recovery rate of this system was 10% in simulation experiments to collect and quantify the viral particles aerosolized by a nebulizer. Using this system, cough samples were collected from 56 influenza A patients. The total viral detection rate was 41% (23/56), and the viral loads varied significantly (from <10, less than the detection limit, to 2240 viral gene copies/cough). Viable viruses were detected from 3 samples with ≤18 plaque forming units per cough sample. The virus detection rates were similar among different groups of patients infected with different viral subtypes and during different influenza seasons. Among patients who did not receive antiviral treatment, viruses were detected in one of six cases in the vaccinated group and four of six cases in the unvaccinated group. We found cases with high viral titers in throat swabs or oral secretions but very low or undetectable in coughs and vice versa suggesting other possible anatomical sites where the viruses might be mixed into the cough. Our system is easy to operate, appropriate for bedside use, and is useful for comparing the viral load in cough samples from influenza patients under various conditions and settings. However, further large-scale studies are warranted to validate our results.",2014 Aug 1,"['Hatagishi, Etsuko', 'Okamoto, Michiko', 'Ohmiya, Suguru', 'Yano, Hisakazu', 'Hori, Toru', 'Saito, Wakana', 'Miki, Hiroshi', 'Suzuki, Yasushi', 'Saito, Reiko', 'Yamamoto, Taro', 'Shoji, Makoto', 'Morisaki, Yoshihisa', 'Sakata, Soichiro', 'Nishimura, Hidekazu']",PLoS One,,,True
18fb0cf6fba22d9478d4f5774f37f6b6bf09f3b0,PMC,Simultaneous Detection and Differentiation of Highly Virulent and Classical Chinese-Type Isolation of PRRSV by Real-Time RT-PCR,http://dx.doi.org/10.1155/2014/809656,PMC4119655,25114934,CC BY,"Porcine reproductive and respiratory syndrome (PRRS) is a leading disease in pig industry worldwide and can result in serious economic losses each year. The PRRS epidemic situation in China has been very complicated since the unprecedented large-scale highly pathogenic PRRS (HP-PRRS) outbreaks in 2006. And now the HP-PRRS virus (HP-PRRSV) and classical North American type PRRSV strains have coexisted in China. Rapid differential detection of the two strains of PRRSV is very important for effective PRRS control. The real-time RT-PCR for simultaneous detection and differentiation of HP-PRRSV and PRRSV by using both SYBR Green and TaqMan probes was developed and validated. Both assays can be used for rapid detection and strain-specific identification of HP-PRRSV and PRRSV. However, the TaqMan probe method had the highest detection rate whereas the conventional RT-PCR was the lowest. The real-time RT-PCR developed based on SYBR Green and TaqMan probe could be used for simultaneous detection and differentiation of HP-PRRSV and PRRSV in China, which will benefit much the PRRS control and research.",2014 Jun 12,"['Xiao, Shuqi', 'Chen, Yaosheng', 'Wang, Liangliang', 'Gao, Jintao', 'Mo, Delin', 'He, Zuyong', 'Liu, Xiaohong']",J Immunol Res,,,True
37142e322bc30493a97e2aff05533919897e39ef,PMC,"Using exercises to improve public health preparedness in Asia, the Middle East and Africa",http://dx.doi.org/10.1186/1756-0500-7-474,PMC4120002,25063987,CC BY,"BACKGROUND: Exercises are increasingly common tools used by the health sector and other sectors to evaluate their preparedness to respond to public health threats. Exercises provide an opportunity for multiple sectors to practice, test and evaluate their response to all types of public health emergencies. The information from these exercises can be used to refine and improve preparedness plans. There is a growing body of literature about the use of exercises among local, state and federal public health agencies in the United States. There is much less information about the use of exercises among public health agencies in other countries and the use of exercises that involve multiple countries. RESULTS: We developed and conducted 12 exercises (four sub-national, five national, three sub-regional) from August 2006 through December 2008. These 12 exercises included 558 participants (average 47) and 137 observers (average 11) from 14 countries. Participants consistently rated the overall quality of the exercises as very good or excellent. They rated the exercises lowest on their ability to identifying key gaps in performance. The vast majority of participants noted that they would use the information they gained at the exercise to improve their organization’s preparedness to respond to an influenza pandemic. Participants felt the exercises were particularly good at raising awareness and understanding about public health threats, assisting in evaluating plans and identifying priorities for improvement, and building relationships that strengthen preparedness and response across sectors and across countries. Participants left the exercises with specific ideas about the most important actions that they should engage in after the exercise such as improved planning coordination across sectors and countries and better training of health workers and response personnel. CONCLUSIONS: These experiences suggest that exercises can be a valuable, low-burden tool to improve emergency preparedness and response in countries around the world. They also demonstrate that countries can work together to develop and conduct successful exercises designed to improve regional preparedness to public health threats. The development of standardized evaluation methods for exercises may be an additional tool to help focus the actions to be taken as a result of the exercise and to improve future exercises. Exercises show great promise as tools to improve public health preparedness across sectors and countries.",2014 Jul 27,"['Dausey, David J', 'Moore, Melinda']",BMC Res Notes,,,True
969c9813397caecc9597daa9679e1bff3bc42635,PMC,Switch from Cap- to Factorless IRES-Dependent 0 and +1 Frame Translation during Cellular Stress and Dicistrovirus Infection,http://dx.doi.org/10.1371/journal.pone.0103601,PMC4121135,25089704,CC BY,"Internal ribosome entry sites (IRES) are utilized by a subset of cellular and viral mRNAs to initiate translation during cellular stress and virus infection when canonical cap-dependent translation is compromised. The intergenic region (IGR) IRES of the Dicistroviridae uses a streamlined mechanism in which it can directly recruit the ribosome in the absence of initiation factors and initiates translation using a non-AUG codon. A subset of IGR IRESs including that from the honey bee viruses can also direct translation of an overlapping +1 frame gene. In this study, we systematically examined cellular conditions that lead to IGR IRES-mediated 0 and +1 frame translation in Drosophila S2 cells. Towards this, a novel bicistronic reporter that exploits the 2A “stop-go” peptide was developed to allow the detection of IRES-mediated translation in vivo. Both 0 and +1 frame translation by the IGR IRES are stimulated under a number of cellular stresses and in S2 cells infected by cricket paralysis virus, demonstrating a switch from cap-dependent to IRES-dependent translation. The regulation of the IGR IRES mechanism ensures that both 0 frame viral structural proteins and +1 frame ORFx protein are optimally expressed during virus infection.",2014 Aug 4,"['Wang, Qing S.', 'Jan, Eric']",PLoS One,,,True
79be2bad7d0442947cec07b060a5b21f8eff7c72,PMC,Involvement of the ERK pathway in the protective effects of glycyrrhizic acid against the MPP(+)-induced apoptosis of dopaminergic neuronal cells,http://dx.doi.org/10.3892/ijmm.2014.1830,PMC4121344,24993693,CC BY,"Glycyrrhizic acid (GA), a major compound separated from Radix Glycyrrhizae, has been shwon to exert various biochemical effects, including neuroprotective effects. In the present study, we investigated the protective effects of GA against 1-methyl-4-phenylpyridinium (MPP(+))-induced damage to differentiated PC12 (DPC12) cells. Compared with the MPP(+)-treated cells, GA markedly improved cell viability, restored mitochondrial dysfunction, suppressed the overexpression of cleaved poly(ADP-ribose) polymerase (PARP), and suppressed the overproduction of lactate dehydrogenase (LDH) and intracellular Ca(2+) overload. The protective effects of GA on cell survival were further confirmed in primary cortical neurons. GA markedly increased the expression of phosphorylated extracellular signal-regulated kinase (p-ERK), as well as its migration from the cytoplasm to nucleus. PD98059, an inhibitor of ERK, blocked GA-enhanced ERK activation and reduced cell viability. However, pre-treatment with GA had no effects on the expression of phosphorylated AKT (p-AKT) and total AKT (t-AKT). These results indicate that the GA-mediated neuroprotective effects are associated with its modulation of multiple anti-apoptotic and pro-apoptotic factors, particularly the ERK signaling pathway. This study provides evidence supporting the use of GA as a potential therapeutic agent for the treatment of neurodegenerative diseases and neuronal injury.",2014 Sep 2,"['TENG, LESHENG', 'KOU, CHUNJIA', 'LU, CHENGYU', 'XU, JIAMING', 'XIE, JING', 'LU, JIAHUI', 'LIU, YAN', 'WANG, ZHENZUO', 'WANG, DI']",Int J Mol Med,,,True
40b7ed2533e026bb5323b85f9d81379ae0f17821,PMC,"ER stress, autophagy, and RNA viruses",http://dx.doi.org/10.3389/fmicb.2014.00388,PMC4122171,25140166,CC BY,"Endoplasmic reticulum (ER) stress is a general term for representing the pathway by which various stimuli affect ER functions. ER stress induces the evolutionarily conserved signaling pathways, called the unfolded protein response (UPR), which compromises the stimulus and then determines whether the cell survives or dies. In recent years, ongoing research has suggested that these pathways may be linked to the autophagic response, which plays a key role in the cell's response to various stressors. Autophagy performs a self-digestion function, and its activation protects cells against certain pathogens. However, the link between the UPR and autophagy may be more complicated. These two systems may act dependently, or the induction of one system may interfere with the other. Experimental studies have found that different viruses modulate these mechanisms to allow them to escape the host immune response or, worse, to exploit the host's defense to their advantage; thus, this topic is a critical area in antiviral research. In this review, we summarize the current knowledge about how RNA viruses, including influenza virus, poliovirus, coxsackievirus, enterovirus 71, Japanese encephalitis virus, hepatitis C virus, and dengue virus, regulate these processes. We also discuss recent discoveries and how these will produce novel strategies for antiviral treatment.",2014 Aug 5,"['Jheng, Jia-Rong', 'Ho, Jin-Yuan', 'Horng, Jim-Tong']",Front Microbiol,,,True
f48a26496eec9f955c65e9d89305c4bc5df2718a,PMC,"IRF7 in the Australian Black Flying Fox, Pteropus alecto: Evidence for a Unique Expression Pattern and Functional Conservation",http://dx.doi.org/10.1371/journal.pone.0103875,PMC4123912,25100081,CC BY,"As the only flying mammal, bats harbor a number of emerging and re-emerging viruses, many of which cause severe diseases in humans and other mammals yet result in no clinical symptoms in bats. As the master regulator of the interferon (IFN)-dependent immune response, IFN regulatory factor 7 (IRF7) plays a central role in innate antiviral immunity. To explore the role of bat IRF7 in the regulation of the IFN response, we performed sequence and functional analysis of IRF7 from the pteropid bat, Pteropus alecto. Our results demonstrate that bat IRF7 retains the ability to bind to MyD88 and activate the IFN response despite unique changes in the MyD88 binding domain. We also demonstrate that bat IRF7 has a unique expression pattern across both immune and non-immune related tissues and is inducible by double-strand RNA. The broad tissue distribution of IRF7 may provide bats with an enhanced ability to rapidly activate the IFN response in a wider range of tissues compared to other mammals. The importance of IRF7 in antiviral activity against the bat reovirus, Pulau virus was confirmed by siRNA knockdown of IRF7 in bat cells resulting in enhanced viral replication. Our results highlight the importance of IRF7 in innate antiviral immunity in bats.",2014 Aug 6,"['Zhou, Peng', 'Cowled, Chris', 'Mansell, Ashley', 'Monaghan, Paul', 'Green, Diane', 'Wu, Lijun', 'Shi, Zhengli', 'Wang, Lin-Fa', 'Baker, Michelle L.']",PLoS One,,,True
f6f669e9a8834d3c4c054d99f3ffd548a40a1059,PMC,ELM: enhanced lowest common ancestor based method for detecting a pathogenic virus from a large sequence dataset,http://dx.doi.org/10.1186/1471-2105-15-254,PMC4124145,25069839,CC BY,"BACKGROUND: Emerging viral diseases, most of which are caused by the transmission of viruses from animals to humans, pose a threat to public health. Discovering pathogenic viruses through surveillance is the key to preparedness for this potential threat. Next generation sequencing (NGS) helps us to identify viruses without the design of a specific PCR primer. The major task in NGS data analysis is taxonomic identification for vast numbers of sequences. However, taxonomic identification via a BLAST search against all the known sequences is a computational bottleneck. DESCRIPTION: Here we propose an enhanced lowest-common-ancestor based method (ELM) to effectively identify viruses from massive sequence data. To reduce the computational cost, ELM uses a customized database composed only of viral sequences for the BLAST search. At the same time, ELM adopts a novel criterion to suppress the rise in false positive assignments caused by the small database. As a result, identification by ELM is more than 1,000 times faster than the conventional methods without loss of accuracy. CONCLUSIONS: We anticipate that ELM will contribute to direct diagnosis of viral infections. The web server and the customized viral database are freely available at http://bioinformatics.czc.hokudai.ac.jp/ELM/. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2105-15-254) contains supplementary material, which is available to authorized users.",2014 Jul 28,"['Ueno, Keisuke', 'Ishii, Akihiro', 'Ito, Kimihito']",BMC Bioinformatics,,,False
fd1910cd1f9847cf0b72bbcf0d94447807c9de66,PMC,ELM: enhanced lowest common ancestor based method for detecting a pathogenic virus from a large sequence dataset,http://dx.doi.org/10.1186/1471-2105-15-254,PMC4124145,25069839,CC BY,"BACKGROUND: Emerging viral diseases, most of which are caused by the transmission of viruses from animals to humans, pose a threat to public health. Discovering pathogenic viruses through surveillance is the key to preparedness for this potential threat. Next generation sequencing (NGS) helps us to identify viruses without the design of a specific PCR primer. The major task in NGS data analysis is taxonomic identification for vast numbers of sequences. However, taxonomic identification via a BLAST search against all the known sequences is a computational bottleneck. DESCRIPTION: Here we propose an enhanced lowest-common-ancestor based method (ELM) to effectively identify viruses from massive sequence data. To reduce the computational cost, ELM uses a customized database composed only of viral sequences for the BLAST search. At the same time, ELM adopts a novel criterion to suppress the rise in false positive assignments caused by the small database. As a result, identification by ELM is more than 1,000 times faster than the conventional methods without loss of accuracy. CONCLUSIONS: We anticipate that ELM will contribute to direct diagnosis of viral infections. The web server and the customized viral database are freely available at http://bioinformatics.czc.hokudai.ac.jp/ELM/. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2105-15-254) contains supplementary material, which is available to authorized users.",2014 Jul 28,"['Ueno, Keisuke', 'Ishii, Akihiro', 'Ito, Kimihito']",BMC Bioinformatics,,,True
4826b9556f50d690979be891d770b33e25003440,PMC,Update in Pathogenesis and Prospective in Treatment of Necrotizing Enterocolitis,http://dx.doi.org/10.1155/2014/543765,PMC4124648,25147804,CC BY,"Necrotizing enterocolitis (NEC) is among the most common and devastating diseases in neonates and, despite the significant advances in neonatal clinical and basic science investigations, its etiology is largely understood, specific treatment strategies are lacking, and morbidity and mortality remain high. Improvements in the understanding of pathogenesis of NEC may have therapeutic consequences. Pharmacologic inhibition of toll-like receptor signaling, the use of novel nutritional strategies, and microflora modulation may represent novel promising approaches to the prevention and treatment of NEC. This review, starting from the recent acquisitions in the pathogenic mechanisms of NEC, focuses on current and possible therapeutic perspectives.",2014 Jul 17,"['Terrin, Gianluca', 'Scipione, Antonella', 'De Curtis, Mario']",Biomed Res Int,,,True
2ee32c492fb088bca33f2b2409baa37d488dae5c,PMC,Virus-Specific Regulatory T Cells Ameliorate Encephalitis by Repressing Effector T Cell Functions from Priming to Effector Stages,http://dx.doi.org/10.1371/journal.ppat.1004279,PMC4125232,25102154,CC BY,"Several studies have demonstrated the presence of pathogen-specific Foxp3(+) CD4 regulatory T cells (Treg) in infected animals, but little is known about where and how these cells affect the effector T cell responses and whether they are more suppressive than bulk Treg populations. We recently showed the presence of both epitope M133-specific Tregs (M133 Treg) and conventional CD4 T cells (M133 Tconv) in the brains of mice with coronavirus-induced encephalitis. Here, we provide new insights into the interactions between pathogenic Tconv and Tregs responding to the same epitope. M133 Tregs inhibited the proliferation but not initial activation of M133 Tconv in draining lymph nodes (DLN). Further, M133 Tregs inhibited migration of M133 Tconv from the DLN. In addition, M133 Tregs diminished microglia activation and decreased the number and function of Tconv in the infected brain. Thus, virus-specific Tregs inhibited pathogenic CD4 T cell responses during priming and effector stages, particularly those recognizing cognate antigen, and decreased mortality and morbidity without affecting virus clearance. These cells are more suppressive than bulk Tregs and provide a targeted approach to ameliorating immunopathological disease in infectious settings.",2014 Aug 7,"['Zhao, Jingxian', 'Zhao, Jincun', 'Perlman, Stanley']",PLoS Pathog,,,True
526919a3d53c54d8c3d0d6b3ba24c77f3a665e1a,PMC,"Molecular Detection of Adenoviruses, Rhabdoviruses, and Paramyxoviruses in Bats from Kenya",http://dx.doi.org/10.4269/ajtmh.13-0664,PMC4125246,24865685,CC BY,"We screened 217 bats of at least 20 species from 17 locations in Kenya during July and August of 2006 for the presence of adenovirus, rhabdovirus, and paramyxovirus nucleic acids using generic reverse transcription polymerase chain reaction (RT-PCR) and PCR assays. Of 217 bat fecal swabs examined, 4 bats were adenovirus DNA-positive, 11 bats were paramyxovirus RNA-positive, and 2 bats were rhabdovirus RNA-positive. Three bats were coinfected by two different viruses. By sequence comparison and phylogenetic analysis, the Kenya bat paramyxoviruses and rhabdoviruses from this study may represent novel viral lineages within their respective families; the Kenya bat adenoviruses could not be confirmed as novel, because the same region sequences from other known bat adenovirus genomes for comparison were lacking. Our study adds to previous evidence that bats carry diverse, potentially zoonotic viruses and may be coinfected with more than one virus.",2014 Aug 6,"['Conrardy, Christina', 'Tao, Ying', 'Kuzmin, Ivan V.', 'Niezgoda, Michael', 'Agwanda, Bernard', 'Breiman, Robert F.', 'Anderson, Larry J.', 'Rupprecht, Charles E.', 'Tong, Suxiang']",Am J Trop Med Hyg,,,True
0a4ff36a0de0c6c9efdcc2f20e3223a31e4c05a0,PMC,Single detection of human bocavirus 1 with a high viral load in severe respiratory tract infections in previously healthy children,http://dx.doi.org/10.1186/1471-2334-14-424,PMC4125703,25078257,CC BY,"BACKGROUND: Human bocavirus is a newly discovered parvovirus. Multiple studies have confirmed the presence of human bocavirus1 (HBoV1) in respiratory tract samples of children. The viral load, presentation of single detection and its role as a causative agent of severe respiratory tract infections have not been thoroughly elucidated. METHODS: We investigated the presence of HBoV1 by quantitative polymerase chain reaction (PCR) of nasopharyngeal aspirate specimens from 1229 children hospitalized for respiratory tract infections. The samples were analyzed for 15 respiratory viruses by PCR and 7 respiratory viruses by viral culture. RESULTS: At least one virus was detected in 652 (53.1%) of 1229 children, and two or more viruses were detected in 266 (21.6%) children. HBoV1 was detected in 127 children (10.3%), in which 66/127 (52%) of the cases were the only HBoV1 virus detected. Seasonal variation was observed with a high HBoV1 infection rate in summer. A cutoff value of 10(7) copies/mL was used to distinguish high and low HBoV1 viral loads in the nasopharyngeal aspirates. High viral loads of HBoV1 were noted predominantly in the absence of other viral agents (28/39, 71.8%) whereas there was primarily co-detection in cases of low HBoV1 viral loads (50/88, 56.8%). There were no differences in the clinical symptoms and severity between HBoV1 single detection and co-detection. In cases of HBoV1 single detection, the high viral load group was more prevalent among children with dyspnea and wheezing than was the low viral load group (42.9% vs. 23.7%, P = 0.036; 60.7% vs. 31.6%, P = 0.018). In clinical severity, a significant difference was recorded (25.0% vs. 5.3%, P = 0.003) between high viral load and low viral load groups. Of the HBoV1 positive patients associated with severe respiratory tract infections, 10/18 (55.6%) patients belonged to the HBoV1 high viral load group, and 7/10 (70%) patients had cases of HBoV1 single detection. CONCLUSIONS: HBoV1 at a high viral load is not frequently found in co-detection with other respiratory viruses, and a single detection with a high viral load could be an etiological agent of severe respiratory tract infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-424) contains supplementary material, which is available to authorized users.",2014 Jul 30,"['Zhou, Lili', 'Zheng, Shouyan', 'Xiao, Qiuyan', 'Ren, Luo', 'Xie, Xiaohong', 'Luo, Jian', 'Wang, Lijia', 'Huang, Ailong', 'Liu, Wei', 'Liu, Enmei']",BMC Infect Dis,,,True
3128ce331b8e280214991a3c775c895045ccfa70,PMC,Anti-inflammatory effects of Lactococcus lactis NCDO 2118 during the remission period of chemically induced colitis,http://dx.doi.org/10.1186/1757-4749-6-33,PMC4126083,25110521,CC BY,"BACKGROUND: Many probiotic bacteria have been described as promising tools for the treatment and prevention of inflammatory bowel diseases (IBDs). Most of these bacteria are lactic acid bacteria, which are part of the healthy human microbiota. However, little is known about the effects of transient bacteria present in normal diets, including Lactococcus lactis. METHODS: In the present study, we analysed the immunomodulatory effects of three L. lactis strains in vitro using intestinal epithelial cells. L. lactis NCDO 2118 was administered for 4 days to C57BL/6 mice during the remission period of colitis induced by dextran sodium sulphate (DSS). RESULTS: Only one strain, L. lactis NCDO 2118, was able to reduce IL-1β-induced IL-8 secretion in Caco-2 cells, suggesting a potential anti-inflammatory effect. Oral treatment using L. lactis NCDO 2118 resulted in a milder form of recurrent colitis than that observed in control diseased mice. This protective effect was not attributable to changes in secretory IgA (sIgA); however, NCDO 2118 administration was associated with an early increase in IL-6 production and sustained IL-10 production in colonic tissue. Mice fed L. lactis NCDO 2118 had an increased number of regulatory CD4(+) T cells (Tregs) bearing surface TGF-β in its latent form (Latency-associated peptide-LAP) in the mesenteric lymph nodes and spleen. CONCLUSIONS: Here, we identified a new probiotic strain with a potential role in the treatment of IBD, and we elucidated some of the mechanisms underlying its anti-inflammatory effect.",2014 Jul 29,"['Luerce, Tessalia Diniz', 'Gomes-Santos, Ana Cristina', 'Rocha, Clarissa Santos', 'Moreira, Thais Garcias', 'Cruz, Déborah Nogueira', 'Lemos, Luísa', 'Sousa, Adna Luciana', 'Pereira, Vanessa Bastos', 'de Azevedo, Marcela', 'Moraes, Kátia', 'Cara, Denise Carmona', 'LeBlanc, Jean Guy', 'Azevedo, Vasco', 'Faria, Ana Maria Caetano', 'Miyoshi, Anderson']",Gut Pathog,,,True
d887a0239eb93e1f9eed94d50126ba28157c4675,PMC,The impact of the interferon-lambda family on the innate and adaptive immune response to viral infections,http://dx.doi.org/10.1038/emi.2014.51,PMC4126180,26038748,CC BY,"Type-III interferons (IFN-λ, IFNL) are the most recently described family of IFNs. This family of innate cytokines are increasingly being ascribed pivotal roles in host–pathogen interactions. Herein, we will review the accumulating evidence detailing the immune biology of IFNL during viral infection, and the implications of this novel information on means to advance the development of therapies and vaccines against existing and emerging pathogens. IFNLs exert antiviral effects via induction of IFN-stimulated genes. Common single nucleotide polymorphisms (SNPs) in the IFNL3, IFNL4 and the IFNL receptor α-subunit genes have been strongly associated with IFN-α-based treatment of chronic hepatitis C virus infection. The clinical impact of these SNPs may be dependent on the status of viral infection (acute or chronic) and the potential to develop viral resistance. Another important function of IFNLs is macrophage and dendritic cell polarization, which prime helper T-cell activation and proliferation. It has been demonstrated that IFNL increase Th1- and reduce Th2-cytokines. Therefore, can such SNPs affect the IFNL signaling and thereby modulate the Th1/Th2 balance during infection? In turn, this may influence the subsequent priming of cytotoxic T cells versus antibody-secreting B cells, with implications for the breadth and durability of the host response.",2014 Jul 16,"['Egli, Adrian', 'Santer, Deanna M', ""O'Shea, Daire"", 'Tyrrell, D Lorne', 'Houghton, Michael']",Emerg Microbes Infect,,,True
cddbec166688aaf25aa6e2e6dc76a90668ba9e9d,PMC,A Membrane Topology Model for Human Interferon Inducible Transmembrane Protein 1,http://dx.doi.org/10.1371/journal.pone.0104341,PMC4126714,25105503,CC BY,"InterFeron Inducible TransMembrane proteins 1–3 (IFITM1, IFITM2 and IFITM3) are a family of proteins capable of inhibiting the cellular entry of numerous human and animal viruses. IFITM1-3 are unique amongst the currently described viral restriction factors in their apparent ability to block viral entry. This restrictive property is dependant on the localisation of the proteins to plasma and endosomal membranes, which constitute the main portals of viral entry into cells. The topology of the IFITM proteins within cell membranes is an unresolved aspect of their biology. Here we present data from immunofluorescence microscopy, protease cleavage, biotin-labelling and immuno-electron microscopy assays, showing that human IFITM1 has a membrane topology in which the N-terminal domain resides in the cytoplasm, and the C-terminal domain is extracellular. Furthermore, we provide evidence that this topology is conserved for all of the human interferon-induced IFITM proteins. This model is consistent with that recently proposed for murine IFITM3, but differs from that proposed for murine IFITM1.",2014 Aug 8,"['Weston, Stuart', 'Czieso, Stephanie', 'White, Ian J.', 'Smith, Sarah E.', 'Kellam, Paul', 'Marsh, Mark']",PLoS One,,,True
167b459cba8933f49d8cb5585f442a68fe326361,PMC,Cellular Proteins Associated with the Interior and Exterior of Vesicular Stomatitis Virus Virions,http://dx.doi.org/10.1371/journal.pone.0104688,PMC4126742,25105980,CC BY,"Virus particles (virions) often contain not only virus-encoded but also host-encoded proteins. Some of these host proteins are enclosed within the virion structure, while others, in the case of enveloped viruses, are embedded in the host-derived membrane. While many of these host protein incorporations are likely accidental, some may play a role in virus infectivity, replication and/or immunoreactivity in the next host. Host protein incorporations may be especially important in therapeutic applications where large numbers of virus particles are administered. Vesicular stomatitis virus (VSV) is the prototypic rhabdovirus and a candidate vaccine, gene therapy and oncolytic vector. Using mass spectrometry, we previously examined cell type dependent host protein content of VSV virions using intact (“whole”) virions purified from three cell lines originating from different species. Here we aimed to determine the localization of host proteins within the VSV virions by analyzing: i) whole VSV virions; and ii) whole VSV virions treated with Proteinase K to remove all proteins outside the viral envelope. A total of 257 proteins were identified, with 181 identified in whole virions and 183 identified in Proteinase K treated virions. Most of these proteins have not been previously shown to be associated with VSV. Functional enrichment analysis indicated the most overrepresented categories were proteins associated with vesicles, vesicle-mediated transport and protein localization. Using western blotting, the presence of several host proteins, including some not previously shown in association with VSV (such as Yes1, Prl1 and Ddx3y), was confirmed and their relative quantities in various virion fractions determined. Our study provides a valuable inventory of virion-associated host proteins for further investigation of their roles in the replication cycle, pathogenesis and immunoreactivity of VSV.",2014 Aug 8,"['Moerdyk-Schauwecker, Megan', 'Hwang, Sun-Il', 'Grdzelishvili, Valery Z.']",PLoS One,,,True
c8adc8df36e5301e6455b55be70e3164b9de66a7,PMC,The Consequences of a Lab Escape of a Potential Pandemic Pathogen,http://dx.doi.org/10.3389/fpubh.2014.00116,PMC4128296,25157347,CC BY,,2014 Aug 11,"['Klotz, Lynn C.', 'Sylvester, Edward J.']",Front Public Health,,,True
5c8323be8a418f5df5d877da4a51720e9aa60425,PMC,Herpes simplex virus type 1 and Alzheimer’s disease: increasing evidence for a major role of the virus,http://dx.doi.org/10.3389/fnagi.2014.00202,PMC4128394,25157230,CC BY,"Herpes simplex virus type 1 (HSV1), when present in brain of carriers of the type 4 allele of the apolipoprotein E gene (APOE), has been implicated as a major factor in Alzheimer’s disease (AD). It is proposed that virus is normally latent in many elderly brains but reactivates periodically (as in the peripheral nervous system) under certain conditions, for example stress, immunosuppression, and peripheral infection, causing cumulative damage and eventually development of AD. Diverse approaches have provided data that explicitly support, directly or indirectly, these concepts. Several have confirmed HSV1 DNA presence in human brains, and the HSV1-APOE-ε4 association in AD. Further, studies on HSV1-infected APOE-transgenic mice have shown that APOE-e4 animals display a greater potential for viral damage. Reactivated HSV1 can cause direct and inflammatory damage, probably involving increased formation of beta amyloid (Aβ) and of AD-like tau (P-tau)—changes found to occur in HSV1-infected cell cultures. Implicating HSV1 further in AD is the discovery that HSV1 DNA is specifically localized in amyloid plaques in AD. Other relevant, harmful effects of infection include the following: dynamic interactions between HSV1 and amyloid precursor protein (APP), which would affect both viral and APP transport; induction of toll-like receptors (TLRs) in HSV1-infected astrocyte cultures, which has been linked to the likely effects of reactivation of the virus in brain. Several epidemiological studies have shown, using serological data, an association between systemic infections and cognitive decline, with HSV1 particularly implicated. Genetic studies too have linked various pathways in AD with those occurring on HSV1 infection. In relation to the potential usage of antivirals to treat AD patients, acyclovir (ACV) is effective in reducing HSV1-induced AD-like changes in cell cultures, and valacyclovir, the bioactive form of ACV, might be most effective if combined with an antiviral that acts by a different mechanism, such as intravenous immunoglobulin (IVIG).",2014 Aug 11,"Itzhaki, Ruth F.",Front Aging Neurosci,,,True
6f6da38ab5fa77f94deb29bfa51504be4ebd018b,PMC,Chinese patent medicines for the treatment of the common cold: a systematic review of randomized clinical trials,http://dx.doi.org/10.1186/1472-6882-14-273,PMC4129119,25074623,CC BY,"BACKGROUND: Many Chinese patent medicines (CPMs) have been authorized by the Chinese State of Food and Drug Administration for the treatment of the common cold. A number of clinical trials have been conducted and published. However, there is no systematic review or meta-analysis on their efficacy and safety for the common cold to justify their clinical use. METHODS: We searched CENTRAL, MEDLINE, EMBASE, SinoMed, CNKI, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites for published and unpublished randomized clinical trials (RCTs) of CPMs for the common cold till 31 March 2013. Revman 5.2 software was used for data analysis with effect estimate presented as relative risk (RR) and mean difference (MD) with a 95% confidence interval (CI). RESULTS: A total of five RCTs were identified. All of the RCTs were of high risk of bias with flawed study design and poor methodological quality. All RCTs included children aged between 6 months to 14 years. Results of individual trials showed that Shuanghuanglian oral liquid (RR 4.00; 95% CI: 2.26 to 7.08), and Xiaoer Resuqing oral liquid (RR 1.43; 95% CI: 1.15 to 1.77) had higher cure rates compared with antivirus drugs. Most of the trials did not report adverse events, and the safety of CPMs was still uncertain. CONCLUSIONS: Some CPMs showed a potential positive effect for the common cold on cure rate. However, due to the poor methodology quality and the defects in the clinical design of the included RCTs, such as the lack of placebo controlled trials, the inappropriate comparison intervention and outcome measurement, the confirmative conclusions on the beneficial effect of CPMs for the common cold could not be drawn.",2014 Jul 30,"['Chen, Wei', 'Liu, Bo', 'Wang, Li-qiong', 'Ren, Jun', 'Liu, Jian-ping']",BMC Complement Altern Med,,,True
f4c43e4ae49ca69dbac32620bd0a73ecbb683b91,PMC,Exploring the Innate Immunological Response of an Alternative Nonhuman Primate Model of Infectious Disease; the Common Marmoset,http://dx.doi.org/10.1155/2014/913632,PMC4129158,25170519,CC BY,"The common marmoset (Callithrix jacchus) is increasingly being utilised as a nonhuman primate model for human disease, ranging from autoimmune to infectious disease. In order to fully exploit these models, meaningful comparison to the human host response is necessary. Commercially available reagents, primarily targeted to human cells, were utilised to assess the phenotype and activation status of key immune cell types and cytokines in naive and infected animals. Single cell suspensions of blood, spleen, and lung were examined. Generally, the phenotype of cells was comparable between humans and marmosets, with approximately 63% of all lymphocytes in the blood of marmosets being T cells, 25% B-cells, and 12% NK cells. The percentage of neutrophils in marmoset blood were more similar to human values than mouse values. Comparison of the activation status of cells following experimental systemic or inhalational infection exhibited different trends in different tissues, most obvious in cell types active in the innate immune response. This work significantly enhances the ability to understand the immune response in these animals and fortifies their use as models of infectious disease.",2014 Jul 22,"['Nelson, M.', 'Loveday, M.']",J Immunol Res,,,True
4ceca734c7185a61184a7e464e454b7f7d958dba,PMC,"Etiology of Severe Childhood Pneumonia in The Gambia, West Africa, Determined by Conventional and Molecular Microbiological Analyses of Lung and Pleural Aspirate Samples",http://dx.doi.org/10.1093/cid/ciu384,PMC4130311,24867789,CC BY,"Molecular analyses of lung aspirates from Gambian children with severe pneumonia detected pathogens more frequently than did culture and showed a predominance of bacteria, principally Streptococcus pneumoniae, >75% being of serotypes covered by current pneumococcal conjugate vaccines. Multiple pathogens were detected frequently, notably Haemophilus influenzae (mostly nontypeable) together with S. pneumoniae.",2014 Sep 1,"['Howie, Stephen R. C.', 'Morris, Gerard A. J.', 'Tokarz, Rafal', 'Ebruke, Bernard E.', 'Machuka, Eunice M.', 'Ideh, Readon C.', 'Chimah, Osaretin', 'Secka, Ousman', 'Townend, John', 'Dione, Michel', 'Oluwalana, Claire', 'Njie, Malick', 'Jallow, Mariatou', 'Hill, Philip C.', 'Antonio, Martin', 'Greenwood, Brian', 'Briese, Thomas', 'Mulholland, Kim', 'Corrah, Tumani', 'Lipkin, W. Ian', 'Adegbola, Richard A.']",Clin Infect Dis,,,True
70f3c90a651224f9292378da905af4ec635d5f43,PMC,Need of surveillance response systems to combat Ebola outbreaks and other emerging infectious diseases in African countries,http://dx.doi.org/10.1186/2049-9957-3-29,PMC4130433,25120913,CC BY,"There is growing concern in Sub-Saharan Africa about the spread of the Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever, and the public health burden that it ensues. Since 1976, there have been 885,343 suspected and laboratory confirmed cases of EVD and the disease has claimed 2,512 cases and 932 fatality in West Africa. There are certain requirements that must be met when responding to EVD outbreaks and this process could incur certain challenges. For the purposes of this paper, five have been identified: (i) the deficiency in the development and implementation of surveillance response systems against Ebola and others infectious disease outbreaks in Africa; (ii) the lack of education and knowledge resulting in an EVD outbreak triggering panic, anxiety, psychosocial trauma, isolation and dignity impounding, stigmatisation, community ostracism and resistance to associated socio-ecological and public health consequences; (iii) limited financial resources, human technical capacity and weak community and national health system operational plans for prevention and control responses, practices and management; (iv) inadequate leadership and coordination; and (v) the lack of development of new strategies, tools and approaches, such as improved diagnostics and novel therapies including vaccines which can assist in preventing, controlling and containing Ebola outbreaks as well as the spread of the disease. Hence, there is an urgent need to develop and implement an active early warning alert and surveillance response system for outbreak response and control of emerging infectious diseases. Understanding the unending risks of transmission dynamics and resurgence is essential in implementing rapid effective response interventions tailored to specific local settings and contexts. Therefore, the following actions are recommended: (i) national and regional inter-sectorial and trans-disciplinary surveillance response systems that include early warnings, as well as critical human resources development, must be quickly adopted by allied ministries and organisations in African countries in epidemic and pandemic responses; (ii) harnessing all stakeholders commitment and advocacy in sustained funding, collaboration, communication and networking including community participation to enhance a coordinated responses, as well as tracking and prompt case management to combat challenges; (iii) more research and development in new drug discovery and vaccines; and (iv) understanding the involvement of global health to promote the establishment of public health surveillance response systems with functions of early warning, as well as monitoring and evaluation in upholding research-action programmes and innovative interventions.",2014 Aug 5,"['Tambo, Ernest', 'Ugwu, Emmanuel Chidiebere', 'Ngogang, Jeane Yonkeu']",Infect Dis Poverty,,,True
7b4eded72a4f06ae298b78f07953e3f45f853aa3,PMC,Need of surveillance response systems to combat Ebola outbreaks and other emerging infectious diseases in African countries,http://dx.doi.org/10.1186/2049-9957-3-29,PMC4130433,25120913,CC BY,"There is growing concern in Sub-Saharan Africa about the spread of the Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever, and the public health burden that it ensues. Since 1976, there have been 885,343 suspected and laboratory confirmed cases of EVD and the disease has claimed 2,512 cases and 932 fatality in West Africa. There are certain requirements that must be met when responding to EVD outbreaks and this process could incur certain challenges. For the purposes of this paper, five have been identified: (i) the deficiency in the development and implementation of surveillance response systems against Ebola and others infectious disease outbreaks in Africa; (ii) the lack of education and knowledge resulting in an EVD outbreak triggering panic, anxiety, psychosocial trauma, isolation and dignity impounding, stigmatisation, community ostracism and resistance to associated socio-ecological and public health consequences; (iii) limited financial resources, human technical capacity and weak community and national health system operational plans for prevention and control responses, practices and management; (iv) inadequate leadership and coordination; and (v) the lack of development of new strategies, tools and approaches, such as improved diagnostics and novel therapies including vaccines which can assist in preventing, controlling and containing Ebola outbreaks as well as the spread of the disease. Hence, there is an urgent need to develop and implement an active early warning alert and surveillance response system for outbreak response and control of emerging infectious diseases. Understanding the unending risks of transmission dynamics and resurgence is essential in implementing rapid effective response interventions tailored to specific local settings and contexts. Therefore, the following actions are recommended: (i) national and regional inter-sectorial and trans-disciplinary surveillance response systems that include early warnings, as well as critical human resources development, must be quickly adopted by allied ministries and organisations in African countries in epidemic and pandemic responses; (ii) harnessing all stakeholders commitment and advocacy in sustained funding, collaboration, communication and networking including community participation to enhance a coordinated responses, as well as tracking and prompt case management to combat challenges; (iii) more research and development in new drug discovery and vaccines; and (iv) understanding the involvement of global health to promote the establishment of public health surveillance response systems with functions of early warning, as well as monitoring and evaluation in upholding research-action programmes and innovative interventions.",2014 Aug 5,"['Tambo, Ernest', 'Ugwu, Emmanuel Chidiebere', 'Ngogang, Jeane Yonkeu']",Infect Dis Poverty,,,False
108b012df7e6ae774a2a83243c0662f376637426,PMC,Porcine Epidemic Diarrhea Virus RNA Present in Commercial Spray-Dried Porcine Plasma Is Not Infectious to Naïve Pigs,http://dx.doi.org/10.1371/journal.pone.0104766,PMC4130536,25116479,CC BY,"Porcine epidemic diarrhea virus emerged in North America in April 2013 and has since been identified in 30 U.S. States, Canada and Mexico. The rapid spread of PEDV has raised concerns about the role of feed and particularly pork-by-product components such as spray-dried porcine plasma (SDPP) in PEDV transmission. The aim of this study was to determine the infectivity of PEDV RNA present in commercial SDPP. Specifically, 40 3-week-old PEDV naïve pigs were randomly assigned to one of five treatment groups. At day post inoculation (dpi) 0, NEG-CONTROL pigs were sham-inoculated, PEDV-CONTROL pigs received cell culture propagated PEDV, and SDPP-CONTROL pigs were switched to a diet with 5% SDPP containing 5.1±0.1 log(10) PEDV RNA copies/g. To evaluate a potential positive effect of anti-PEDV antibodies in SDPP on PEDV challenge, four days prior to PEDV challenge the pigs in the SDPP-PEDV group were switched to and remained on a 5% SDPP diet through dpi 28. Another group, EGG-PEDV, was orally administered a commercial egg-derived liquid PEDV globulin product from dpi -4 through 6. All PEDV-CONTROL pigs began shedding PEDV in feces by dpi 3 and seroconverted between dpi 7 and 14, whereas pigs in NEG-CONTROL and SDPP-CONTROL groups remained PEDV RNA negative and did not seroconvert to PEDV for the study duration. This indicates no evidence of infectivity of the PEDV RNA in the SDPP lot utilized. Furthermore, under the study conditions SDPP or egg-derived liquid PEDV globulin addition did not significantly alter PEDV-shedding or overall disease course after experimental challenge.",2014 Aug 12,"['Opriessnig, Tanja', 'Xiao, Chao-Ting', 'Gerber, Priscilla F.', 'Zhang, Jianqiang', 'Halbur, Patrick G.']",PLoS One,,,True
21469fd00f33c1dcdde68abf4b8da0508b7fe2d8,PMC,Self-Assembly and Release of Peste des Petits Ruminants Virus-Like Particles in an Insect Cell-Baculovirus System and Their Immunogenicity in Mice and Goats,http://dx.doi.org/10.1371/journal.pone.0104791,PMC4130610,25117931,CC BY,"Peste des petits ruminants (PPR) is an acute, febrile, viral disease of small ruminants that has a significant economic impact. For many viral diseases, vaccination with virus-like particles (VLPs) has shown considerable promise as a prophylactic approach; however, the processes of assembly and release of peste des petits ruminants virus (PPRV) VLPs are not well characterized, and their immunogenicity in the host is unknown. In this study, VLPs of PPRV were generated in a baculovirus system through simultaneous expression of PPRV matrix (M) protein and hemaglutin in (H) or fusion (F) protein. The released VLPs showed morphology similar to that of the native virus particles. Subcutaneous injection of these VLPs (PPRV-H, PPRV-F) into mice and goats elicited PPRV-specific IgG production, increased the levels of virus neutralizing antibodies, and promoted lymphocyte proliferation. Without adjuvants, the immune response induced by the PPRV-H VLPs was comparable to that obtained using equivalent amounts of PPRV vaccine. Thus, our results demonstrated that VLPs containing PPRV M protein and H or F protein are potential “differentiating infected from vaccinated animals” (DIVA) vaccine candidates for the surveillance and eradication of PPR.",2014 Aug 12,"['Li, Wenchao', 'Jin, Hongyan', 'Sui, Xiukun', 'Zhao, Zhanzhong', 'Yang, Chenghuai', 'Wang, Wenquan', 'Li, Junping', 'Li, Gang']",PLoS One,,,True
8dada285162e466f7867f6b657853905bd778933,PMC,Using core competencies to build an evaluative framework: outcome assessment of the University of Guelph Master of Public Health program,http://dx.doi.org/10.1186/1472-6920-14-158,PMC4131476,25078124,CC BY,"BACKGROUND: Master of Public Health programs have been developed across Canada in response to the need for graduate-level trained professionals to work in the public health sector. The University of Guelph recently conducted a five-year outcome assessment using the Core Competencies for Public Health in Canada as an evaluative framework to determine whether graduates are receiving adequate training, and identify areas for improvement. METHODS: A curriculum map of core courses and an online survey of University of Guelph Master of Public Health graduates comprised the outcome assessment. The curriculum map was constructed by evaluating course outlines, assignments, and content to determine the extent to which the Core Competencies were covered in each course. Quantitative survey results were characterized using descriptive statistics. Qualitative survey results were analyzed to identify common themes and patterns in open-ended responses. RESULTS: The University of Guelph Master of Public Health program provided a positive learning environment in which graduates gained proficiency across the Core Competencies through core and elective courses, meaningful practicums, and competent faculty. Practice-based learning environments, particularly in collaboration with public health organizations, were deemed to be beneficial to students’ learning experiences. CONCLUSIONS: The Core Competencies and graduate surveys can be used to conduct a meaningful and informative outcome assessment. We encourage other Master of Public Health programs to conduct their own outcome assessments using a similar framework, and disseminate these results in order to identify best practices and strengthen the Canadian graduate public health education system.",2014 Jul 31,"['Britten, Nicole', 'Wallar, Lauren E', 'McEwen, Scott A', 'Papadopoulos, Andrew']",BMC Med Educ,,,True
af86dce0ad626fff251552974a6b9245a0038e14,PMC,Using core competencies to build an evaluative framework: outcome assessment of the University of Guelph Master of Public Health program,http://dx.doi.org/10.1186/1472-6920-14-158,PMC4131476,25078124,CC BY,"BACKGROUND: Master of Public Health programs have been developed across Canada in response to the need for graduate-level trained professionals to work in the public health sector. The University of Guelph recently conducted a five-year outcome assessment using the Core Competencies for Public Health in Canada as an evaluative framework to determine whether graduates are receiving adequate training, and identify areas for improvement. METHODS: A curriculum map of core courses and an online survey of University of Guelph Master of Public Health graduates comprised the outcome assessment. The curriculum map was constructed by evaluating course outlines, assignments, and content to determine the extent to which the Core Competencies were covered in each course. Quantitative survey results were characterized using descriptive statistics. Qualitative survey results were analyzed to identify common themes and patterns in open-ended responses. RESULTS: The University of Guelph Master of Public Health program provided a positive learning environment in which graduates gained proficiency across the Core Competencies through core and elective courses, meaningful practicums, and competent faculty. Practice-based learning environments, particularly in collaboration with public health organizations, were deemed to be beneficial to students’ learning experiences. CONCLUSIONS: The Core Competencies and graduate surveys can be used to conduct a meaningful and informative outcome assessment. We encourage other Master of Public Health programs to conduct their own outcome assessments using a similar framework, and disseminate these results in order to identify best practices and strengthen the Canadian graduate public health education system.",2014 Jul 31,"['Britten, Nicole', 'Wallar, Lauren E', 'McEwen, Scott A', 'Papadopoulos, Andrew']",BMC Med Educ,,,False
76121941b87c781e6bdb9872304d87a74cc0f782,PMC,Using core competencies to build an evaluative framework: outcome assessment of the University of Guelph Master of Public Health program,http://dx.doi.org/10.1186/1472-6920-14-158,PMC4131476,25078124,CC BY,"BACKGROUND: Master of Public Health programs have been developed across Canada in response to the need for graduate-level trained professionals to work in the public health sector. The University of Guelph recently conducted a five-year outcome assessment using the Core Competencies for Public Health in Canada as an evaluative framework to determine whether graduates are receiving adequate training, and identify areas for improvement. METHODS: A curriculum map of core courses and an online survey of University of Guelph Master of Public Health graduates comprised the outcome assessment. The curriculum map was constructed by evaluating course outlines, assignments, and content to determine the extent to which the Core Competencies were covered in each course. Quantitative survey results were characterized using descriptive statistics. Qualitative survey results were analyzed to identify common themes and patterns in open-ended responses. RESULTS: The University of Guelph Master of Public Health program provided a positive learning environment in which graduates gained proficiency across the Core Competencies through core and elective courses, meaningful practicums, and competent faculty. Practice-based learning environments, particularly in collaboration with public health organizations, were deemed to be beneficial to students’ learning experiences. CONCLUSIONS: The Core Competencies and graduate surveys can be used to conduct a meaningful and informative outcome assessment. We encourage other Master of Public Health programs to conduct their own outcome assessments using a similar framework, and disseminate these results in order to identify best practices and strengthen the Canadian graduate public health education system.",2014 Jul 31,"['Britten, Nicole', 'Wallar, Lauren E', 'McEwen, Scott A', 'Papadopoulos, Andrew']",BMC Med Educ,,,False
b9440a58f12e8325569e686c0aaf6eed458075ba,PMC,Using core competencies to build an evaluative framework: outcome assessment of the University of Guelph Master of Public Health program,http://dx.doi.org/10.1186/1472-6920-14-158,PMC4131476,25078124,CC BY,"BACKGROUND: Master of Public Health programs have been developed across Canada in response to the need for graduate-level trained professionals to work in the public health sector. The University of Guelph recently conducted a five-year outcome assessment using the Core Competencies for Public Health in Canada as an evaluative framework to determine whether graduates are receiving adequate training, and identify areas for improvement. METHODS: A curriculum map of core courses and an online survey of University of Guelph Master of Public Health graduates comprised the outcome assessment. The curriculum map was constructed by evaluating course outlines, assignments, and content to determine the extent to which the Core Competencies were covered in each course. Quantitative survey results were characterized using descriptive statistics. Qualitative survey results were analyzed to identify common themes and patterns in open-ended responses. RESULTS: The University of Guelph Master of Public Health program provided a positive learning environment in which graduates gained proficiency across the Core Competencies through core and elective courses, meaningful practicums, and competent faculty. Practice-based learning environments, particularly in collaboration with public health organizations, were deemed to be beneficial to students’ learning experiences. CONCLUSIONS: The Core Competencies and graduate surveys can be used to conduct a meaningful and informative outcome assessment. We encourage other Master of Public Health programs to conduct their own outcome assessments using a similar framework, and disseminate these results in order to identify best practices and strengthen the Canadian graduate public health education system.",2014 Jul 31,"['Britten, Nicole', 'Wallar, Lauren E', 'McEwen, Scott A', 'Papadopoulos, Andrew']",BMC Med Educ,,,False
4c9d7e3db46a6026e1554f2fa3df4f93645381e1,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,True
0863338d4ec43e14a5438e5935bea4ff7cebeba0,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
49f04c6a31256ab8fb38bdcc329a6744248287fe,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
90d84b5b33ae2fb3c8d04b2ddb22d38fc9812740,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
87b5b5ddaa9c4adce29690c99a8aa92ff94c9203,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
e3ced319adf75d3a8442f1f94aaa5e79f9c74a99,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
25e667ff5a9a2b7f23192c2d34ef8edef4831c3d,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
b9d414deb6745c5410577dd00a9a483f65e4b340,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
2e6cb10cda7335535d59ea42b3d1e61f8eb4d8b6,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
d57b9b3170641624374a5a8211179699202adade,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
729870e5682b37d66e76f187a00584d00f725ea8,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
ebc78f92bc422103204b417df443754c8bf11ed4,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
fd421b0d1a42db7b23a87c7c7fb668d54437d70a,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
f7adc8de97c5f8d8ab6f6cad71bbef9c50790629,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
e9b657e17fc500733811c3cdb06bf6da3fb2adc3,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
ef43f8ba1afa11245e1f85c36bf74f4640ac4f1f,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
674aee78f478c1b628f00b9824de6230585be142,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
cddb100b1e41224a63a2362be678d773426b4615,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
7e8e7ba9af4f10d5ec6bfda422d0f5251a5f0f2b,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
4aa3212174a384b9e1b5bd2f58023d60b1d1bd2d,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
49369bef87aedbc56dc328357faae0db1a40a517,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
36e5a1e939633cc6a8b4fa2dc7d70f9dbe5f0ee8,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
767767546b54da4b2a51840674c68adfd4e1a0bf,PMC,Detection of Middle East respiratory syndrome coronavirus using reverse transcription loop-mediated isothermal amplification (RT-LAMP),http://dx.doi.org/10.1186/1743-422X-11-139,PMC4132226,25103205,CC BY,"BACKGROUND: The first documented case of Middle East Respiratory Syndrome coronavirus (MERS-CoV) occurred in 2012, and outbreaks have continued ever since, mainly in Saudi Arabia. MERS-CoV is primarily diagnosed using a real-time RT-PCR assay, with at least two different genomic targets required for a positive diagnosis according to the case definition of The World Health Organization (WHO) as of 3 July 2013. Therefore, it is urgently necessary to develop as many specific genetic diagnostic methods as possible to allow stable diagnosis of MERS-CoV infections. METHODS: Reverse transcription-loop-mediated isothermal amplification (RT-LAMP) is a genetic diagnostic method used widely for the detection of viral pathogens, which requires only a single temperature for amplification, and can be completed in less than 1 h. This study developed a novel RT-LAMP assay for detecting MERS-CoV using primer sets targeting a conserved nucleocapsid protein region. RESULTS: The RT-LAMP assay was capable of detecting as few as 3.4 copies of MERS-CoV RNA, and was highly specific, with no cross-reaction to other respiratory viruses. Pilot experiments to detect MERS-CoV from medium containing pharyngeal swabs inoculated with pre-titrated viruses were also performed. The RT-LAMP assay exhibited sensitivity similar to that of MERS-CoV real-time RT-PCR. CONCLUSIONS: These results suggest that the RT-LAMP assay described here is a useful tool for the diagnosis and epidemiologic surveillance of human MERS-CoV infections.",2014 Aug 8,"['Shirato, Kazuya', 'Yano, Takuya', 'Senba, Syouhei', 'Akachi, Shigehiro', 'Kobayashi, Takashi', 'Nishinaka, Takamichi', 'Notomi, Tsugunori', 'Matsuyama, Shutoku']",Virol J,,,True
5bc94c9cd8e4bcae0c56a4343f6f60cdc0effa9c,PMC,Complete Genome Sequence of Porcine Epidemic Diarrhea Virus in Vietnam,http://dx.doi.org/10.1128/genomeA.00753-14,PMC4132615,25125639,CC BY,"Porcine epidemic diarrhea virus (PEDV) has emerged in Vietnam since 2009. Herein, full-length genome sequences are reported for three PEDV isolates from pigs displaying severe diarrhea from farms located in northern and southern provinces of Vietnam. The results provide more understanding of the molecular characteristics of PEDV in Vietnam.",2014 Aug 14,"['Vui, Dam Thi', 'Tung, Nguyen', 'Inui, Ken', 'Slater, Steven', 'Nilubol, Dachrit']",Genome Announc,,,True
7c36bbbb2505c7eefacad040c39bd5b167969ad2,PMC,The PDZ-Binding Motif of Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Is a Determinant of Viral Pathogenesis,http://dx.doi.org/10.1371/journal.ppat.1004320,PMC4133396,25122212,CC BY,"A recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) lacking the envelope (E) protein is attenuated in vivo. Here we report that E protein PDZ-binding motif (PBM), a domain involved in protein-protein interactions, is a major determinant of virulence. Elimination of SARS-CoV E protein PBM by using reverse genetics caused a reduction in the deleterious exacerbation of the immune response triggered during infection with the parental virus and virus attenuation. Cellular protein syntenin was identified to bind the E protein PBM during SARS-CoV infection by using three complementary strategies, yeast two-hybrid, reciprocal coimmunoprecipitation and confocal microscopy assays. Syntenin redistributed from the nucleus to the cell cytoplasm during infection with viruses containing the E protein PBM, activating p38 MAPK and leading to the overexpression of inflammatory cytokines. Silencing of syntenin using siRNAs led to a decrease in p38 MAPK activation in SARS-CoV infected cells, further reinforcing their functional relationship. Active p38 MAPK was reduced in lungs of mice infected with SARS-CoVs lacking E protein PBM as compared with the parental virus, leading to a decreased expression of inflammatory cytokines and to virus attenuation. Interestingly, administration of a p38 MAPK inhibitor led to an increase in mice survival after infection with SARS-CoV, confirming the relevance of this pathway in SARS-CoV virulence. Therefore, the E protein PBM is a virulence domain that activates immunopathology most likely by using syntenin as a mediator of p38 MAPK induced inflammation.",2014 Aug 14,"['Jimenez-Guardeño, Jose M.', 'Nieto-Torres, Jose L.', 'DeDiego, Marta L.', 'Regla-Nava, Jose A.', 'Fernandez-Delgado, Raul', 'Castaño-Rodriguez, Carlos', 'Enjuanes, Luis']",PLoS Pathog,,,True
298ebce4397c9735f69cb5fcf9ad82881eead18f,PMC,The HIV-1 Envelope Transmembrane Domain Binds TLR2 through a Distinct Dimerization Motif and Inhibits TLR2-Mediated Responses,http://dx.doi.org/10.1371/journal.ppat.1004248,PMC4133399,25121610,CC BY,"HIV-1 uses a number of means to manipulate the immune system, to avoid recognition and to highjack signaling pathways. HIV-1 infected cells show limited Toll-Like Receptor (TLR) responsiveness via as yet unknown mechanisms. Using biochemical and biophysical approaches, we demonstrate that the trans-membrane domain (TMD) of the HIV-1 envelope (ENV) directly interacts with TLR2 TMD within the membrane milieu. This interaction attenuates TNFα, IL-6 and MCP-1 secretion in macrophages, induced by natural ligands of TLR2 both in in vitro and in vivo models. This was associated with decreased levels of ERK phosphorylation. Furthermore, mutagenesis demonstrated the importance of a conserved GxxxG motif in driving this interaction within the membrane milieu. The administration of the ENV TMD in vivo to lipotechoic acid (LTA)/Galactosamine-mediated septic mice resulted in a significant decrease in mortality and in tissue damage, due to the weakening of systemic macrophage activation. Our findings suggest that the TMD of ENV is involved in modulation of the innate immune response during HIV infection. Furthermore, due to the high functional homology of viral ENV proteins this function may be a general character of viral-induced immune modulation.",2014 Aug 14,"['Reuven, Eliran Moshe', 'Ali, Mohammad', 'Rotem, Etai', 'Schwarzter, Roland', 'Gramatica, Andrea', 'Futerman, Anthony H.', 'Shai, Yechiel']",PLoS Pathog,,,True
a4e41dcddb7c0eb538defbf19602371176f1f97c,PMC,Effect of human movement on airborne disease transmission in an airplane cabin: study using numerical modeling and quantitative risk analysis,http://dx.doi.org/10.1186/1471-2334-14-434,PMC4133625,25098254,CC BY,"BACKGROUND: Airborne transmission of respiratory infectious disease in indoor environment (e.g. airplane cabin, conference room, hospital, isolated room and inpatient ward) may cause outbreaks of infectious diseases, which may lead to many infection cases and significantly influences on the public health. This issue has received more and more attentions from academics. This work investigates the influence of human movement on the airborne transmission of respiratory infectious diseases in an airplane cabin by using an accurate human model in numerical simulation and comparing the influences of different human movement behaviors on disease transmission. METHODS: The Eulerian–Lagrangian approach is adopted to simulate the dispersion and deposition of the expiratory aerosols. The dose–response model is used to assess the infection risks of the occupants. The likelihood analysis is performed as a hypothesis test on the input parameters and different human movement pattern assumptions. An in-flight SARS outbreak case is used for investigation. A moving person with different moving speeds is simulated to represent the movement behaviors. A digital human model was used to represent the detailed profile of the occupants, which was obtained by scanning a real thermal manikin using the 3D laser scanning system. RESULTS: The analysis results indicate that human movement can strengthen the downward transport of the aerosols, significantly reduce the overall deposition and removal rate of the suspended aerosols and increase the average infection risk in the cabin. The likelihood estimation result shows that the risk assessment results better fit the outcome of the outbreak case when the movements of the seated passengers are considered. The intake fraction of the moving person is significantly higher than most of the seated passengers. CONCLUSIONS: The infection risk distribution in the airplane cabin highly depends on the movement behaviors of the passengers and the index patient. The walking activities of the crew members and the seated passengers can significantly increase their personal infection risks. Taking the influence of the movement of the seated passengers and the index patient into consideration is necessary and important. For future studies, investigations on the behaviors characteristics of the passengers during flight will be useful and helpful for infection control. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-434) contains supplementary material, which is available to authorized users.",2014 Aug 6,"['Han, Zhuyang', 'Sze To, Gin Nam', 'Fu, Sau Chung', 'Chao, Christopher Yu-Hang', 'Weng, Wenguo', 'Huang, Quanyi']",BMC Infect Dis,,,True
692fedb674101b505fb28fe7b96e552ed224c07d,PMC,Multiplex Degenerate Primer Design for Targeted Whole Genome Amplification of Many Viral Genomes,http://dx.doi.org/10.1155/2014/101894,PMC4137498,25157264,CC BY,"Background. Targeted enrichment improves coverage of highly mutable viruses at low concentration in complex samples. Degenerate primers that anneal to conserved regions can facilitate amplification of divergent, low concentration variants, even when the strain present is unknown. Results. A tool for designing multiplex sets of degenerate sequencing primers to tile overlapping amplicons across multiple whole genomes is described. The new script, run_tiled_primers, is part of the PriMux software. Primers were designed for each segment of South American hemorrhagic fever viruses, tick-borne encephalitis, Henipaviruses, Arenaviruses, Filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, and Japanese encephalitis virus. Each group is highly diverse with as little as 5% genome consensus. Primer sets were computationally checked for nontarget cross reactions against the NCBI nucleotide sequence database. Primers for murine hepatitis virus were demonstrated in the lab to specifically amplify selected genes from a laboratory cultured strain that had undergone extensive passage in vitro and in vivo. Conclusions. This software should help researchers design multiplex sets of primers for targeted whole genome enrichment prior to sequencing to obtain better coverage of low titer, divergent viruses. Applications include viral discovery from a complex background and improved sensitivity and coverage of rapidly evolving strains or variants in a gene family.",2014 Aug 3,"['Gardner, Shea N.', 'Jaing, Crystal J.', 'Elsheikh, Maher M.', 'Peña, José', 'Hysom, David A.', 'Borucki, Monica K.']",Adv Bioinformatics,,,True
de4137cea11509b6caf359fd5c66a215a1e8390f,PMC,Rapid Detection of Mycobacterium tuberculosis by Recombinase Polymerase Amplification,http://dx.doi.org/10.1371/journal.pone.0103091,PMC4138011,25118698,CC BY,"Improved access to effective tests for diagnosing tuberculosis (TB) has been designated a public health priority by the World Health Organisation. In high burden TB countries nucleic acid based TB tests have been restricted to centralised laboratories and specialised research settings. Requirements such as a constant electrical supply, air conditioning and skilled, computer literate operators prevent implementation of such tests in many settings. Isothermal DNA amplification technologies permit the use of simpler, less energy intensive detection platforms more suited to low resource settings that allow the accurate diagnosis of a disease within a short timeframe. Recombinase Polymerase Amplification (RPA) is a rapid, low temperature isothermal DNA amplification reaction. We report here RPA-based detection of Mycobacterium tuberculosis complex (MTC) DNA in <20 minutes at 39°C. Assays for two MTC specific targets were investigated, IS6110 and IS1081. When testing purified MTC genomic DNA, limits of detection of 6.25 fg (IS6110) and 20 fg (IS1081)were consistently achieved. When testing a convenience sample of pulmonary specimens from suspected TB patients, RPA demonstrated superior accuracy to indirect fluorescence microscopy. Compared to culture, sensitivities for the IS1081 RPA and microscopy were 91.4% (95%CI: 85, 97.9) and 86.1% (95%CI: 78.1, 94.1) respectively (n = 71). Specificities were 100% and 88.6% (95% CI: 80.8, 96.1) respectively. For the IS6110 RPA and microscopy sensitivities of 87.5% (95%CI: 81.7, 93.2) and 70.8% (95%CI: 62.9, 78.7) were obtained (n = 90). Specificities were 95.4 (95% CI: 92.3,98.1) and 88% (95% CI: 83.6, 92.4) respectively. The superior specificity of RPA for detecting tuberculosis was due to the reduced ability of fluorescence microscopy to distinguish Mtb complex from other acid fast bacteria. The rapid nature of the RPA assay and its low energy requirement compared to other amplification technologies suggest RPA-based TB assays could be of use for integration into a point-of-care test for use in resource constrained settings.",2014 Aug 13,"['Boyle, David S.', 'McNerney, Ruth', 'Teng Low, Hwee', 'Leader, Brandon Troy', 'Pérez-Osorio, Ailyn C.', 'Meyer, Jessica C.', ""O'Sullivan, Denise M."", 'Brooks, David G.', 'Piepenburg, Olaf', 'Forrest, Matthew S.']",PLoS One,,,True
5538bf904bcd32abf4ca1dbe9fc7e6c7514ebeda,PMC,A Quantitative Prioritisation of Human and Domestic Animal Pathogens in Europe,http://dx.doi.org/10.1371/journal.pone.0103529,PMC4138073,25136810,CC BY,"Disease or pathogen risk prioritisations aid understanding of infectious agent impact within surveillance or mitigation and biosecurity work, but take significant development. Previous work has shown the H-(Hirsch-)index as an alternative proxy. We present a weighted risk analysis describing infectious pathogen impact for human health (human pathogens) and well-being (domestic animal pathogens) using an objective, evidence-based, repeatable approach; the H-index. This study established the highest H-index European pathogens. Commonalities amongst pathogens not included in previous surveillance or risk analyses were examined. Differences between host types (humans/animals/zoonotic) in pathogen H-indices were explored as a One Health impact indicator. Finally, the acceptability of the H-index proxy for animal pathogen impact was examined by comparison with other measures. 57 pathogens appeared solely in the top 100 highest H-indices (1) human or (2) animal pathogens list, and 43 occurred in both. Of human pathogens, 66 were zoonotic and 67 were emerging, compared to 67 and 57 for animals. There were statistically significant differences between H-indices for host types (humans, animal, zoonotic), and there was limited evidence that H-indices are a reasonable proxy for animal pathogen impact. This work addresses measures outlined by the European Commission to strengthen climate change resilience and biosecurity for infectious diseases. The results include a quantitative evaluation of infectious pathogen impact, and suggest greater impacts of human-only compared to zoonotic pathogens or scientific under-representation of zoonoses. The outputs separate high and low impact pathogens, and should be combined with other risk assessment methods relying on expert opinion or qualitative data for priority setting, or could be used to prioritise diseases for which formal risk assessments are not possible because of data gaps.",2014 Aug 19,"['McIntyre, K. Marie', 'Setzkorn, Christian', 'Hepworth, Philip J.', 'Morand, Serge', 'Morse, Andrew P.', 'Baylis, Matthew']",PLoS One,,,True
2afa3da371e5495dd55f0b4dde4ae7700eaf99d6,PMC,"Rhinitis, Asthma and Respiratory Infections among Adults in Relation to the Home Environment in Multi-Family Buildings in Sweden",http://dx.doi.org/10.1371/journal.pone.0105125,PMC4138153,25136984,CC BY,"Risk factors for rhinitis, asthma and respiratory infections in the home environment were studied by a questionnaire survey. Totally 5775 occupants (≥18 years old) from a stratified random sample of multi-family buildings in Sweden participated (46%). 51.0% had rhinitis in the last 3 months (current rhinitis); 11.5% doctor diagnosed asthma; 46.4% respiratory infections in the last 3 months and 11.9% antibiotic medication for respiratory infections in the last 12 months. Associations between home environment and health were analyzed by multiple logistic regression, controlling for gender, age and smoking and mutual adjustment. Buildings constructed during 1960–1975 were risk factors for day time breathlessness (OR = 1.53, 95%CI 1.03–2.29). And those constructed during 1976–1985 had more current rhinitis (OR = 1.43, 95%CI 1.12–1.84) and respiratory infections (OR = 1.46, 95%CI 1.21–1.78). Cities with higher population density had more current rhinitis (p = 0.008) and respiratory infections (p<0.001). Rented apartments had more current rhinitis (OR = 1.23, 95%CI 1.07–1.40), wheeze (OR = 1.20, 95%CI 1.02–1.41), day time breathlessness (OR = 1.31, 95%CI 1.04–1.66) and respiratory infections (OR = 1.13, 95%CI 1.01–1.26). Living in colder parts of the country was a risk factor for wheeze (p = 0.03) and night time breathlessness (p = 0.002). Building dampness was a risk factor for wheeze (OR = 1.42, 95%CI 1.08–1.86) and day time breathlessness (OR = 1.57, 95%CI 1.09–2.27). Building dampness was a risk factor for health among those below 66 years old. Odor at home was a risk factor for doctor diagnosed asthma (OR = 1.49, 95%CI 1.08–2.06) and current asthma (OR = 1.52, 95%CI 1.03–2.24). Environmental tobacco smoke (ETS) was a risk factor for current asthma (OR = 1.53, 95%CI 1.09–2.16). Window pane condensation was a risk factor for antibiotic medication for respiratory infections (OR = 1.41, 95%CI 1.10–1.82). In conclusion, rhinitis, asthma and respiratory infections were related to a number of factors in the home environment. Certain building years (1961–1985), building dampness, window pane condensation and odor in the dwelling may be risk factors.",2014 Aug 19,"['Wang, Juan', 'Engvall, Karin', 'Smedje, Greta', 'Norbäck, Dan']",PLoS One,,,True
22d734ce865dda20bbbbd2695ffe67cb5bb10445,PMC,A canine model of experimental infection with Leishmania (L.) mexicana,http://dx.doi.org/10.1186/1756-3305-7-361,PMC4138396,25108307,CC BY,"BACKGROUND: Cutaneous leishmaniasis is a tropical disease affecting over one million patients annually and Leishmania (L.) mexicana is one of the major etiological agents in the Americas. Here we established the first experimental infection of L. (L.) mexicana in canids. METHODS: Beagle dogs were infected intradermally with culture-derived L. (L.) mexicana. We followed skin ulcer development, histopathological signs, parasite burden and the immune status of the infected dogs. RESULTS: All infected dogs developed uniform oval-craterform ulcers similar to those observed in humans, associated with mixed T helper 1/T helper 2 immune responses. Parasites were detected in the healed lesions 15 weeks post-infection. Higher anti-Leishmania IgG levels correlated with larger lesions and high IgG1/IgG2 ratio was associated with some level of splenomegaly. CONCLUSIONS: The canine model described in this work will be of use for further understanding of L. (L.) mexicana immunopathogenensis, and for drug and vaccine development.",2014 Aug 9,"['Cruz-Chan, Julio Vladimir', 'Carmen Aguilar-Cetina, Amarú del', 'Estefanía Villanueva-Lizama, Liliana', 'Pablo Martínez-Vega, Pedro', 'Jesús Ramírez-Sierra, Maria', 'Enrique Rosado-Vallado, Miguel', 'Leonardo Guillermo-Cordero, José', 'Dumonteil, Eric']",Parasit Vectors,,,True
c290f9617c78697d527d8a58bdbd8ef9af47fcfc,PMC,"Metagenomic Survey for Viruses in Western Arctic Caribou, Alaska, through Iterative Assembly of Taxonomic Units",http://dx.doi.org/10.1371/journal.pone.0105227,PMC4139337,25140520,CC0,"Pathogen surveillance in animals does not provide a sufficient level of vigilance because it is generally confined to surveillance of pathogens with known economic impact in domestic animals and practically nonexistent in wildlife species. As most (re-)emerging viral infections originate from animal sources, it is important to obtain insight into viral pathogens present in the wildlife reservoir from a public health perspective. When monitoring living, free-ranging wildlife for viruses, sample collection can be challenging and availability of nucleic acids isolated from samples is often limited. The development of viral metagenomics platforms allows a more comprehensive inventory of viruses present in wildlife. We report a metagenomic viral survey of the Western Arctic herd of barren ground caribou (Rangifer tarandus granti) in Alaska, USA. The presence of mammalian viruses in eye and nose swabs of 39 free-ranging caribou was investigated by random amplification combined with a metagenomic analysis approach that applied exhaustive iterative assembly of sequencing results to define taxonomic units of each metagenome. Through homology search methods we identified the presence of several mammalian viruses, including different papillomaviruses, a novel parvovirus, polyomavirus, and a virus that potentially represents a member of a novel genus in the family Coronaviridae.",2014 Aug 20,"['Schürch, Anita C.', 'Schipper, Debby', 'Bijl, Maarten A.', 'Dau, Jim', 'Beckmen, Kimberlee B.', 'Schapendonk, Claudia M. E.', 'Raj, V. Stalin', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.', 'Tryland, Morten', 'Smits, Saskia L.']",PLoS One,,,True
d1913c3e3106846c33b96d7276edc1d2a62b1a1e,PMC,Serum Diamine Oxidase as a Hemorrhagic Shock Biomarker in a Rabbit Model,http://dx.doi.org/10.1371/journal.pone.0102285,PMC4140717,25144315,CC BY,"BACKGROUND: In prolonged hemorrhagic shock, reductions in intestinal mucosal blood perfusion lead to mucosal barrier damage and systemic inflammation. Gastrointestinal failure in critically ill patients has a poor prognosis, so early assessment of mucosal barrier injury in shock patients is clinically relevant. Unfortunately, there is no serum marker that can accurately assess intestinal ischemia-reperfusion injury. OBJECTIVE: The aim of this study was to assess if serum diamine oxidase levels can reflect intestinal mucosal injury subsequent to prolonged hemorrhagic shock. METHODS: Thirty New Zealand white rabbits were divided into three groups: a control group, a medium blood pressure (BP) group (exsanguinated to a shock BP of 50 to 41 mm Hg), and a low BP group (exsanguinated to a shock blood pressure of 40 to 31 mm Hg), in which the shock BP was sustained for 180 min prior to fluid resuscitation. RESULTS: The severity of hemorrhagic shock in the low BP group was significantly greater than that of the medium BP group according to the post-resuscitation BP, serum tumor necrosis factor (TNF)-α, and arterial lactate. Intestinal damage was significantly more severe in the low BP group according to Chiu’s scoring, claudin-1, intercellular adhesion molecule (ICAM)-1, and myeloperoxidase expression. Serum diamine oxidase was significantly increased in the low BP group compared to the medium BP and control groups and was negatively correlated with shock BP. CONCLUSION: Serum diamine oxidase can be used as a serological marker in evaluating intestinal injury and shows promise as an indicator of hemorrhagic shock severity.",2014 Aug 21,"['Zhao, Liang', 'Luo, Lin', 'Jia, Weikun', 'Xiao, Juan', 'Huang, Gang', 'Tian, Geng', 'Li, Jingwei', 'Xiao, Yingbin']",PLoS One,,,True
4d392425fe3005f145fdfa835421ff0aa5fe0104,PMC,Early-Life Hepatitis E Infection in Pigs: The Importance of Maternally-Derived Antibodies,http://dx.doi.org/10.1371/journal.pone.0105527,PMC4140806,25144763,CC BY,"Passive immunity (PI), acquired through colostrum intake, is essential for piglet protection against pathogens. Maternally-derived antibodies (MDAs) can decrease the transmission of pathogens between individuals by reducing shedding from infected animals and/or susceptibility of naïve animals. Only a limited number of studies, however, have been carried out to quantify the level of protection conferred by PI in terms of transmission. In the present study, an original modeling framework was designed to estimate parameters governing the transmission of infectious agents in the presence and absence of PI. This epidemiological model accounts for the distribution of PI duration and two different forces of infection depending on the serological status of animals after colostrum intake. A Bayesian approach (Metropolis-Hastings algorithm) was used for parameter estimation. The impact of PI on hepatitis E virus transmission in piglets was investigated using longitudinal serological data from six pig farms. A strong impact of PI was highlighted, the efficiency of transmission being on average 13 times lower in piglets with maternally-derived antibodies than in fully susceptible animals (range: 5–21). Median infection-free survival ages, based on herd-specific estimates, ranged between 8.7 and 13.8 weeks in all but one herd. Indeed, this herd exhibited a different profile with a relatively low prevalence of infected pigs (50% at slaughter age) despite the similar proportions of passively immune individuals after colostrum intake. These results suggest that the age at HEV infection is not strictly dependent upon the proportion of piglets with PI but is also linked to farm-specific husbandry (mingling of piglets after weaning) and hygiene practices. The original methodology developed here, using population-based longitudinal serological data, was able to demonstrate the relative impact of MDAs on the transmission of infectious agents.",2014 Aug 21,"['Andraud, Mathieu', 'Casas, Maribel', 'Pavio, Nicole', 'Rose, Nicolas']",PLoS One,,,True
78f939545e7217684295ab63900119ab1ebdb173,PMC,Infection with MERS-CoV Causes Lethal Pneumonia in the Common Marmoset,http://dx.doi.org/10.1371/journal.ppat.1004250,PMC4140844,25144235,CC0,"The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans. The suitability of the marmoset as a MERS-CoV model was tested by inoculation via combined intratracheal, intranasal, oral and ocular routes. Most of the marmosets developed a progressive severe pneumonia leading to euthanasia of some animals. Extensive lesions were evident in the lungs of all animals necropsied at different time points post inoculation. Some animals were also viremic; high viral loads were detected in the lungs of all infected animals, and total RNAseq demonstrated the induction of immune and inflammatory pathways. This is the first description of a severe, partially lethal, disease model of MERS-CoV, and as such will have a major impact on the ability to assess the efficacy of vaccines and treatment strategies as well as allowing more detailed pathogenesis studies.",2014 Aug 21,"['Falzarano, Darryl', 'de Wit, Emmie', 'Feldmann, Friederike', 'Rasmussen, Angela L.', 'Okumura, Atsushi', 'Peng, Xinxia', 'Thomas, Matthew J.', 'van Doremalen, Neeltje', 'Haddock, Elaine', 'Nagy, Lee', 'LaCasse, Rachel', 'Liu, Tingting', 'Zhu, Jiang', 'McLellan, Jason S.', 'Scott, Dana P.', 'Katze, Michael G.', 'Feldmann, Heinz', 'Munster, Vincent J.']",PLoS Pathog,,,True
e840685d875ae1d0d6c08a0176f2151b2765a0d0,PMC,"Proteomics analysis reveals protein expression differences for hypopharyngeal gland activity in the honeybee, Apis mellifera carnica Pollmann",http://dx.doi.org/10.1186/1471-2164-15-665,PMC4141115,25103401,CC BY,"BACKGROUND: Most of the proteins contained in royal jelly (RJ) are secreted from the hypopharyngeal glands (HG) of young bees. Although generic protein composition of RJ has been investigated, little is known about how age-dependent changes on HG secretion affect RJ composition and their biological consequences. In this study, we identified differentially expressed proteins (DEPs) during HG development by using the isobaric tag for relative and absolute quantification (iTRAQ) labeling technique. This proteomic method increases the potential for new protein discovery by improving the identification of low quantity proteins. RESULTS: A total of 1282 proteins were identified from five age groups of worker bees, 284 of which were differentially expressed. 43 (15.1%) of the DEPs were identified for the first time. Comparison of samples at day 6, 9, 12, and 16 of development relative to day 3 led to the unambiguous identification of 112, 117, 127, and 127 DEPs, respectively. The majority of these DEPs were up-regulated in the older worker groups, indicating a substantial change in the pattern of proteins expressed after 3 days. DEPs were identified among all the age groups, suggesting that changes in protein expression during HG ontogeny are concomitant with different states of worker development. A total of 649 proteins were mapped to canonical signaling pathways found in the Kyoto Encyclopedia of Genes and Genomes (KEGG), which were preferentially associated with metabolism and biosynthesis of secondary metabolites. More than 10 key high-abundance proteins were involved in signaling pathways related to ribosome function and protein processing in the endoplasmic reticulum. The results were validated by qPCR. CONCLUSION: Our approach demonstrates that HG experienced important changes in protein expression during its ontogenic development, which supports the secretion of proteins involved in diverse functions in adult workers beyond its traditional role in royal jelly production. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-665) contains supplementary material, which is available to authorized users.",2014 Aug 8,"['Ji, Ting', 'Liu, Zhenguo', 'Shen, Jie', 'Shen, Fang', 'Liang, Qin', 'Wu, Liming', 'Chen, Guohong', 'Corona, Miguel']",BMC Genomics,,,True
9235d0eee63bf8da637b7b63b983d58d2372f0d3,PMC,Genetic Variants of CD209 Associated with Kawasaki Disease Susceptibility,http://dx.doi.org/10.1371/journal.pone.0105236,PMC4141786,25148534,CC BY,"BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis with unknown etiology mainly affecting children in Asian countries. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN, CD209) in humans was showed to trigger an anti-inflammatory cascade and associated with KD susceptibility. This study was conducted to investigate the association between genetic polymorphisms of CD209 and the risk KD. METHODS: A total of 948 subjects (381 KD and 567 controls) were recruited. Nine tagging SNPs (rs8112310, rs4804800, rs11465421, rs1544766, rs4804801, rs2287886, rs735239, rs735240, rs4804804) were selected for TaqMan allelic discrimination assay. Clinical phenotypes, coronary artery lesions (CAL) and intravenous immunoglobulin (IVIG) treatment outcomes were collected for analysis. RESULTS: Significant associations were found between CD209 polymorphisms (rs4804800, rs2287886, rs735240) and the risk of KD. Haplotype analysis for CD209 polymorphisms showed that A/A/G haplotype (P = 0.0002, OR = 1.61) and G/A/G haplotype (P = 0.0365, OR = 1.52) had higher risk of KD as compared with G/G/A haplotype in rs2287886/rs735239/rs735240 pairwise allele analysis. There were no significant association in KD with regards to CAL formation and IVIG treatment responses. CONCLUSION: CD209 polymorphisms were responsible for the susceptibility of KD, but not CAL formation and IVIG treatment responsiveness.",2014 Aug 22,"['Kuo, Ho-Chang', 'Huang, Ying-Hsien', 'Chien, Shu-Chen', 'Yu, Hong-Ren', 'Hsieh, Kai-Sheng', 'Hsu, Yu-Wen', 'Chang, Wei-Chiao']",PLoS One,,,True
5a85b1a03f6d5cebc70bad6027c941a2224f0df0,PMC,"Genomic Characterization of a Circovirus Associated with Fatal Hemorrhagic Enteritis in Dog, Italy",http://dx.doi.org/10.1371/journal.pone.0105909,PMC4141843,25147946,CC BY,"Dog circovirus (DogCV) was identified in an outbreak of enteritis in pups in Italy. The disease was observed in 6 young dachshunds pups of a litter from a breeding kennel and caused the death of 2 dogs. Upon full-genome analysis, the virus detected in one of the dead pups (strain Bari/411–13) was closely related to DogCVs that have been recently isolated in the USA. The present study, if corroborated by further reports, could represent a useful contribution to the knowledge of the pathogenic potential of DogCV and its association with enteritis in dogs.",2014 Aug 22,"['Decaro, Nicola', 'Martella, Vito', 'Desario, Costantina', 'Lanave, Gianvito', 'Circella, Elena', 'Cavalli, Alessandra', 'Elia, Gabriella', 'Camero, Michele', 'Buonavoglia, Canio']",PLoS One,,,True
8c43b5c8a56828ee5687a2b572dc05333c2815a0,PMC,Highlights from the 2014 International Symposium on HIV & Emerging Infectious Diseases (ISHEID): from cART management to the end of the HIV pandemic,http://dx.doi.org/10.1186/1742-6405-11-28,PMC4145833,25165483,CC BY,"The 2014 International Symposium on HIV and Emerging Infectious Diseases (ISHEID) provided a forum for investigators to hear the latest research developments in the clinical management of HIV and HCV infections as well as HIV cure research. Combined anti-retroviral therapy (c-ART) has had a profound impact on the disease prognosis and transformed this infection into a chronic disease. However, HIV is able to persist within the infected host and the pandemic is still growing. The main 2014 ISHEID theme was, hence “Together for a world without HIV and AIDS”. In this report we not only give details on this main topic but also summarize what has been discussed in the areas of HCV coinfection and present a short summary on currently emerging viral diseases.",2014 Aug 21,"['Lafeuillade, Alain', 'Wainberg, Mark', 'Gougeon, Marie-Lise', 'Loes, Sabine Kinloch-de', 'Halfon, Philippe', 'Tissot-Dupont, Hervé']",AIDS Res Ther,,,True
a62bab2887ddd15979d7ef71e48ea7ae3596adf6,PMC,"The Antibody Germline/Maturation Hypothesis, Elicitation of Broadly Neutralizing Antibodies Against HIV-1 and Cord Blood IgM Repertoires",http://dx.doi.org/10.3389/fimmu.2014.00398,PMC4147355,25221552,CC BY,"We have previously observed that all known potent broadly neutralizing antibodies (bnAbs) against HIV-1 are highly divergent from their putative germline predecessors in contrast to bnAbs against viruses causing acute infections such as henipaviruses and SARS CoV, which are much less divergent from their germline counterparts. Consequently, we have hypothesized that germline antibodies may not bind to the HIV-1 envelope glycoprotein (Env) because they are so different compared to the highly somatically mutated HIV-1-specific bnAbs. We have further hypothesized that the immunogenicity of highly conserved epitopes on the HIV-1 envelope glycoproteins (Envs) may be reduced or eliminated by their very weak or absent interactions with germline antibodies and immune responses leading to the elicitation of bnAbs may not be initiated and/or sustained. Even if such responses are initiated, the maturation pathways are so extraordinarily complex that prolonged periods of time may be required for elicitation of bnAbs with defined unique sequences. We provided the initial evidence supporting this antibody germline/maturation hypothesis, which prompted a number of studies to design vaccine immunogens that could bind putative germline predecessors of known bnAbs and to explore complex B cell lineages. However, guiding the immune system through the exceptionally complex antibody maturation pathways to elicit known bnAbs remains a major challenge. Here, we discuss studies exploring the antibody germline/maturation hypothesis as related to elicitation of bnAbs against HIV-1 and present our recent data demonstrating the existence of germline-like precursors of VRC01 antibodies in a human cord blood IgM library.",2014 Aug 28,"['Prabakaran, Ponraj', 'Chen, Weizao', 'Dimitrov, Dimiter S.']",Front Immunol,,,True
52f1664a1d9fae42e3fbc1f19d936c711826a931,PMC,Identification of Cis-Acting Elements on Positive-Strand Subgenomic mRNA Required for the Synthesis of Negative-Strand Counterpart in Bovine Coronavirus,http://dx.doi.org/10.3390/v6082938,PMC4147681,25080125,CC BY,"It has been demonstrated that, in addition to genomic RNA, sgmRNA is able to serve as a template for the synthesis of the negative-strand [(−)-strand] complement. However, the cis-acting elements on the positive-strand [(+)-strand] sgmRNA required for (−)-strand sgmRNA synthesis have not yet been systematically identified. In this study, we employed real-time quantitative reverse transcription polymerase chain reaction to analyze the cis-acting elements on bovine coronavirus (BCoV) sgmRNA 7 required for the synthesis of its (−)-strand counterpart by deletion mutagenesis. The major findings are as follows. (1) Deletion of the 5'-terminal leader sequence on sgmRNA 7 decreased the synthesis of the (−)-strand sgmRNA complement. (2) Deletions of the 3' untranslated region (UTR) bulged stem-loop showed no effect on (−)-strand sgmRNA synthesis; however, deletion of the 3' UTR pseudoknot decreased the yield of (−)-strand sgmRNA. (3) Nucleotides positioned from −15 to −34 of the sgmRNA 7 3'-terminal region are required for efficient (−)-strand sgmRNA synthesis. (4) Nucleotide species at the 3'-most position (−1) of sgmRNA 7 is correlated to the efficiency of (−)-strand sgmRNA synthesis. These results together suggest, in principle, that the 5'- and 3'-terminal sequences on sgmRNA 7 harbor cis-acting elements are critical for efficient (−)-strand sgmRNA synthesis in BCoV.",2014 Jul 30,"['Yeh, Po-Yuan', 'Wu, Hung-Yi']",Viruses,,,True
bc070e8139c6a9087e25333319f8b852aee81836,PMC,Identification of Cis-Acting Elements on Positive-Strand Subgenomic mRNA Required for the Synthesis of Negative-Strand Counterpart in Bovine Coronavirus,http://dx.doi.org/10.3390/v6082938,PMC4147681,25080125,CC BY,"It has been demonstrated that, in addition to genomic RNA, sgmRNA is able to serve as a template for the synthesis of the negative-strand [(−)-strand] complement. However, the cis-acting elements on the positive-strand [(+)-strand] sgmRNA required for (−)-strand sgmRNA synthesis have not yet been systematically identified. In this study, we employed real-time quantitative reverse transcription polymerase chain reaction to analyze the cis-acting elements on bovine coronavirus (BCoV) sgmRNA 7 required for the synthesis of its (−)-strand counterpart by deletion mutagenesis. The major findings are as follows. (1) Deletion of the 5'-terminal leader sequence on sgmRNA 7 decreased the synthesis of the (−)-strand sgmRNA complement. (2) Deletions of the 3' untranslated region (UTR) bulged stem-loop showed no effect on (−)-strand sgmRNA synthesis; however, deletion of the 3' UTR pseudoknot decreased the yield of (−)-strand sgmRNA. (3) Nucleotides positioned from −15 to −34 of the sgmRNA 7 3'-terminal region are required for efficient (−)-strand sgmRNA synthesis. (4) Nucleotide species at the 3'-most position (−1) of sgmRNA 7 is correlated to the efficiency of (−)-strand sgmRNA synthesis. These results together suggest, in principle, that the 5'- and 3'-terminal sequences on sgmRNA 7 harbor cis-acting elements are critical for efficient (−)-strand sgmRNA synthesis in BCoV.",2014 Jul 30,"['Yeh, Po-Yuan', 'Wu, Hung-Yi']",Viruses,,,False
b190452f13e95ef0af0c07243e44a98371fe00eb,PMC,The Coronavirus Nucleocapsid Is a Multifunctional Protein,http://dx.doi.org/10.3390/v6082991,PMC4147684,25105276,CC BY,"The coronavirus nucleocapsid (N) is a structural protein that forms complexes with genomic RNA, interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. Recent studies have confirmed that N is a multifunctional protein. The aim of this review is to highlight the properties and functions of the N protein, with specific reference to (i) the topology; (ii) the intracellular localization and (iii) the functions of the protein.",2014 Aug 7,"['McBride, Ruth', 'van Zyl, Marjorie', 'Fielding, Burtram C.']",Viruses,,,True
f6d2afb2ec44d8656972ea79f8a833143bbeb42b,PMC,Virus-Vectored Influenza Virus Vaccines,http://dx.doi.org/10.3390/v6083055,PMC4147686,25105278,CC BY,"Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines.",2014 Aug 7,"['Tripp, Ralph A.', 'Tompkins, S. Mark']",Viruses,,,True
f87ca9ce6ad3323737c273a36a56a08d050b2d26,PMC,European Bats as Carriers of Viruses with Zoonotic Potential,http://dx.doi.org/10.3390/v6083110,PMC4147689,25123684,CC BY,"Bats are being increasingly recognized as reservoir hosts of highly pathogenic and zoonotic emerging viruses (Marburg virus, Nipah virus, Hendra virus, Rabies virus, and coronaviruses). While numerous studies have focused on the mentioned highly human-pathogenic bat viruses in tropical regions, little is known on similar human-pathogenic viruses that may be present in European bats. Although novel viruses are being detected, their zoonotic potential remains unclear unless further studies are conducted. At present, it is assumed that the risk posed by bats to the general public is rather low. In this review, selected viruses detected and isolated in Europe are discussed from our point of view in regard to their human-pathogenic potential. All European bat species and their roosts are legally protected and some European species are even endangered. Nevertheless, the increasing public fear of bats and their viruses is an obstacle to their protection. Educating the public regarding bat lyssaviruses might result in reduced threats to both the public and the bats.",2014 Aug 13,"['Kohl, Claudia', 'Kurth, Andreas']",Viruses,,,True
b95e82e0343a470f5b39c97eae9f8541e218b76d,PMC,Canine Enteric Coronaviruses: Emerging Viral Pathogens with Distinct Recombinant Spike Proteins,http://dx.doi.org/10.3390/v6083363,PMC4147700,25153347,CC BY,"Canine enteric coronavirus (CCoV) is an alphacoronavirus infecting dogs that is closely related to enteric coronaviruses of cats and pigs. While CCoV has traditionally caused mild gastro-intestinal clinical signs, there are increasing reports of lethal CCoV infections in dogs, with evidence of both gastrointestinal and systemic viral dissemination. Consequently, CCoV is now considered to be an emerging infectious disease of dogs. In addition to the two known serotypes of CCoV, novel recombinant variants of CCoV have been found containing spike protein N-terminal domains (NTDs) that are closely related to those of feline and porcine strains. The increase in disease severity in dogs and the emergence of novel CCoVs can be attributed to the high level of recombination within the spike gene that can occur during infection by more than one CCoV type in the same host.",2014 Aug 22,"['Licitra, Beth N.', 'Duhamel, Gerald E.', 'Whittaker, Gary R.']",Viruses,,,True
b147a9e7654ef4257a7c45cae6606543a7864c80,PMC,FTY720 (fingolimod) modulates the severity of viral-induced encephalomyelitis and demyelination,http://dx.doi.org/10.1186/s12974-014-0138-y,PMC4148542,25138356,CC BY,"BACKGROUND: FTY720 (fingolimod) is the first oral drug approved by the Food and Drug Administration for treatment of patients with the relapsing-remitting form of the human demyelinating disease multiple sclerosis. Evidence suggests that the therapeutic benefit of FTY720 occurs by preventing the egress of lymphocytes from lymph nodes thereby inhibiting the infiltration of disease-causing lymphocytes into the central nervous system (CNS). We hypothesized that FTY720 treatment would affect lymphocyte migration to the CNS and influence disease severity in a mouse model of viral-induced neurologic disease. METHODS: Mice were infected intracranially with the neurotropic JHM strain of mouse hepatitis virus. Infected animals were treated with increasing doses (1, 3 and 10 mg/kg) of FTY720 and morbidity and mortality recorded. Infiltration of inflammatory virus-specific T cells (tetramer staining) into the CNS of FTY720-treated mice was determined using flow cytometry. The effects of FTY720 treatment on virus-specific T cell proliferation, cytokine production and cytolytic activity were also determined. The severity of neuroinflammation and demyelination in FTY720-treated mice was examined by flow cytometry and histopathologically, respectively, in the spinal cords of the mice. RESULTS: Administration of FTY720 to JHMV-infected mice resulted in increased clinical disease severity and mortality. These results correlated with impaired ability to control viral replication (P < 0.05) within the CNS at days 7 and 14 post-infection, which was associated with diminished accumulation of virus-specific CD4+ and CD8+ T cells (P < 0.05) into the CNS. Reduced neuroinflammation in FTY720-treated mice correlated with increased retention of T lymphocytes within draining cervical lymph nodes (P < 0.05). Treatment with FTY720 did not affect virus-specific T cell proliferation, expression of IFN-γ, TNF-α or cytolytic activity. FTY720-treated mice exhibited a reduction in the severity of demyelination associated with dampened neuroinflammation. CONCLUSION: These findings indicate that FTY720 mutes effective anti-viral immune responses through impacting migration and accumulation of virus-specific T cells within the CNS during acute viral-induced encephalomyelitis. FTY720 treatment reduces the severity of neuroinflammatory-mediated demyelination by restricting the access of disease-causing lymphocytes into the CNS but is not associated with viral recrudescence in this model.",2014 Aug 20,"['Blanc, Caroline A', 'Rosen, Hugh', 'Lane, Thomas E']",J Neuroinflammation,,,True
8705d3a93c346b8b21e349c6263e680d844e7aea,PMC,NK Cells in Mucosal Defense against Infection,http://dx.doi.org/10.1155/2014/413982,PMC4150440,25197644,CC BY,"Conventional natural killer cells (NK cells) provide continual surveillance for cancer and rapid responses to infection. They develop in the bone marrow, emerge as either NK precursor cells, immature, or mature cells, and disperse throughout the body. In the periphery NK cells provide critical defense against pathogens and cancer and are noted to develop features of adaptive immune responses. In the tightly regulated and dynamic mucosal tissues, they set up residency via unknown mechanisms and from sources that are yet to be defined. Once resident, they appear to have the ability to functionally mature dependent on the mucosal tissue microenvironment. Mucosal NK cells play a pivotal role in early protection through their cytolytic function and IFNγ production against bacteria, fungi, viruses, and parasitic infections. This review presents what is known about NK cell development and phenotypes of mucosal tissue resident conventional NK cells. The question of how they come to reside in their tissues and published data on their function against pathogens during mucosal infection are discussed. Dissecting major questions highlighted in this review will be important to the further understanding of NK cell homing and functional diversity and improve rational design of NK cell based therapies against mucosal infection.",2014 Aug 14,"['Ivanova, Daria', 'Krempels, Ryan', 'Ryfe, Jennyfer', 'Weitzman, Kaitlyn', 'Stephenson, David', 'Gigley, Jason P.']",Biomed Res Int,,,True
4b138ca6c96ce56fb2db1641847bd7686ca1cdff,PMC,Western Cold and Flu (WeCoF) aerosol study – preliminary results,http://dx.doi.org/10.1186/1756-0500-7-563,PMC4150972,25148847,CC BY,"BACKGROUND: Influenza virus is responsible for annual deaths due to seasonal epidemics and is the cause of major pandemics which have claimed millions of human lives over the last century. Knowledge about respiratory virus transmission is advancing. Spread is likely through the air, but much work remains to be done to characterize the aerosols produced by infected individuals, including viral particle survival and infectivity. Although coughs have been characterized, little work has been done to examine coughs from infected individuals. The WeCoF project aims at providing evidence to support prevention measures to mitigate person-to-person influenza transmission in critical locations, such as hospitals, and during pandemics. FINDINGS: A novel experimental cough chamber facility – the FLUGIE – has been developed to study the far-field aerodynamics and aerosol transport of droplets produced by the coughs from humans naturally-infected with influenza. The flow field of each cough is measured using Particle Image Velocimetry (PIV). A preliminary study involving 12 healthy individuals has been carried out in order to quantify the strengths of their coughs at a distance of 1 m from the mouth. The spatially averaged maximum velocity was determined and the average value was 0.41 m/s across 27 coughs of good data quality. The peak value of velocity was also extracted and compared with the average velocity. CONCLUSIONS: Preliminary results show that there is significant air motion associated with a cough (on the order of 0.5 m/s) as far away as 1 m from the mouth of the healthy person who coughs. The results from this pilot study provide the framework for a more extensive participant recruitment campaign that will encompass a statistically-significant cohort.",2014 Aug 23,"['Savory, Eric', 'Lin, William E', 'Blackman, Karin', 'Roberto, Matthew C', 'Cuthbertson, Lauren R', 'Scott, James A', 'Mubareka, Samira']",BMC Res Notes,,,True
9f548a03c496ef67ce743572cca4201debbf9910,PMC,Ethics of Clinical Science in a Public Health Emergency: Drug Discovery at the Bedside,http://dx.doi.org/10.1080/15265161.2013.813597,PMC4151792,23952822,CC BY,"Clinical research under the usual regulatory constraints may be difficult or even impossible in a public health emergency. Regulators must seek to strike a good balance in granting as wide therapeutic access to new drugs as possible at the same time as gathering sound evidence of safety and effectiveness. To inform current policy, I reexamine the philosophical rationale for restricting new medicines to clinical trials, at any stage and for any population of patients (which resides in the precautionary principle), to show that its objective to protect public health, now or in the future, could soon be defeated in a pandemic. Providing wider therapeutic access and coordinating observations and natural experiments, including service delivery by cluster (wedged cluster trials), may provide such a balance. However, there are important questions of fairness to resolve before any such research can proceed.",2013 Sep 1,"Edwards, Sarah J. L.",Am J Bioeth,,,True
6d08d5d8add16122735dcfa90a4c36f8d2a348ea,PMC,Defensins and Sepsis,http://dx.doi.org/10.1155/2014/180109,PMC4151856,25210703,CC BY,"Sepsis is a leading cause of mortality and morbidity in the critical illness. Multiple immune inflammatory processes take part in the pathogenesis of sepsis. Defensins are endogenous antimicrobial peptides with three disulphide bonds created by six cysteine residues. Besides the intrinsic microbicidal properties, defensins are active players which modulate both innate and adaptive immunity against various infections. Defensins can recruit neutrophils, enhance phagocytosis, chemoattract T cells and dendritic cells, promote complement activation, and induce IL-1β production and pyrotosis. Previous publications have documented that defensins play important roles in a series of immune inflammatory diseases including sepsis. This review aims to briefly summarize in vitro, in vivo, and genetic studies on defensins' effects as well as corresponding mechanisms within sepsis and highlights their promising findings which may be potential targets in future therapies of sepsis.",2014 Aug 19,"['Xie, Guo-Hao', 'Chen, Qi-Xing', 'Cheng, Bao-Li', 'Fang, Xiang-Ming']",Biomed Res Int,,,True
19b9ee3dcd89f01eea3e48b333888b1ce70b296f,PMC,Emergence of Pathogenic Coronaviruses in Cats by Homologous Recombination between Feline and Canine Coronaviruses,http://dx.doi.org/10.1371/journal.pone.0106534,PMC4152292,25180686,CC BY,"Type II feline coronavirus (FCoV) emerged via double recombination between type I FCoV and type II canine coronavirus (CCoV). In this study, two type I FCoVs, three type II FCoVs and ten type II CCoVs were genetically compared. The results showed that three Japanese type II FCoVs, M91-267, KUK-H/L and Tokyo/cat/130627, also emerged by homologous recombination between type I FCoV and type II CCoV and their parent viruses were genetically different from one another. In addition, the 3′-terminal recombination sites of M91-267, KUK-H/L and Tokyo/cat/130627 were different from one another within the genes encoding membrane and spike proteins, and the 5′-terminal recombination sites were also located at different regions of ORF1. These results indicate that at least three Japanese type II FCoVs emerged independently. Sera from a cat experimentally infected with type I FCoV was unable to neutralize type II CCoV infection, indicating that cats persistently infected with type I FCoV may be superinfected with type II CCoV. Our previous study reported that few Japanese cats have antibody against type II FCoV. All of these observations suggest that type II FCoV emerged inside the cat body and is unable to readily spread among cats, indicating that these recombination events for emergence of pathogenic coronaviruses occur frequently.",2014 Sep 2,"['Terada, Yutaka', 'Matsui, Nobutaka', 'Noguchi, Keita', 'Kuwata, Ryusei', 'Shimoda, Hiroshi', 'Soma, Takehisa', 'Mochizuki, Masami', 'Maeda, Ken']",PLoS One,,,True
2fadcd6b5c3ddc519094af150095be7578d8499b,PMC,Topology and biological function of enterovirus non-structural protein 2B as a member of the viroporin family,http://dx.doi.org/10.1186/s13567-014-0087-6,PMC4155101,25163654,CC BY,"Viroporins are a group of transmembrane proteins with low molecular weight that are encoded by many animal viruses. Generally, viroporins are composed of 50–120 amino acid residues and possess a minimum of one hydrophobic region that interacts with the lipid bilayer and leads to dispersion. Viroporins are involved in destroying the morphology of host cells and disturbing their biological functions to complete the life cycle of the virus. The 2B proteins encoded by enteroviruses, which belong to the family Picornaviridae, can form transmembrane pores by oligomerization, increase the permeability of plasma membranes, disturb the homeostasis of calcium in cells, induce apoptosis, and cause autophagy; these abilities are shared among viroporins. The present paper introduces the structure and biological characteristics of various 2B proteins encoded by enteroviruses of the family Picornaviridae and may provide a novel idea for developing antiviral drugs.",2014 Aug 28,"['Ao, Da', 'Sun, Shi-Qi', 'Guo, Hui-Chen']",Vet Res,,,True
34ccc1c615fa5697b5926c7ce5f1ea21bc06f5fa,PMC,Spherules and IBV,http://dx.doi.org/10.4161/bioe.29323,PMC4156489,25482229,CC BY,"Infectious bronchitis virus (IBV) is an economically important virus infecting chickens, causing large losses to the poultry industry globally. While vaccines are available, there is a requirement for novel vaccine strategies due to high strain variation and poor cross-protection. This requires a more detailed understanding of virus-host cell interactions to identify candidates for targeted virus attenuation. One key area of research in the positive sense RNA virus field, due to its central role in virus replication, is the induction of cellular membrane rearrangements by this class of viruses for the assembly of virus replication complexes. In our recent work, we identified the structures induced by IBV during infection of cultured cells, as well as primary cells and ex vivo organ culture. We identified structures novel to the coronavirus family, which strongly resemble replication sites of other positive sense RNA viruses. We have begun to extend this work using recombinant IBVs, which are chimera of different virus strains to study the role of viral proteins in the induction of membrane rearrangements.",2014 Sep 1,"['Maier, Helena J', 'Hawes, Philippa C', 'Keep, Sarah M', 'Britton, Paul']",Bioengineered,,,True
94ba61be5805b1b0caef6716c00ed234be78b021,PMC,The Role of Myeloid Cell Activation and Arginine Metabolism in the Pathogenesis of Virus-Induced Diseases,http://dx.doi.org/10.3389/fimmu.2014.00428,PMC4157561,25250029,CC BY,"When an antiviral immune response is generated, a balance must be reached between two opposing pathways: the production of proinflammatory and cytotoxic effectors that drive a robust antiviral immune response to control the infection and regulators that function to limit or blunt an excessive immune response to minimize immune-mediated pathology and repair tissue damage. Myeloid cells, including monocytes and macrophages, play an important role in this balance, particularly through the activities of the arginine-hydrolyzing enzymes nitric oxide synthase 2 (Nos2; iNOS) and arginase 1 (Arg1). Nitric oxide (NO) production by iNOS is an important proinflammatory mediator, whereas Arg1-expressing macrophages contribute to the resolution of inflammation and wound repair. In the context of viral infections, expression of these enzymes can result in a variety of outcomes for the host. NO has direct antiviral properties against some viruses, whereas during other virus infections NO can mediate immunopathology and/or inhibit the antiviral immune response to promote chronic infection. Arg1 activity not only has important wound healing functions but can also inhibit the antiviral immune response during some viral infections. Thus, depending on the specific virus and the tissue(s) involved, the activity of both of these arginine-hydrolyzing enzymes can either exacerbate or limit the severity of virus-induced disease. In this review, we will discuss a variety of viral infections, including HIV, SARS-CoV, LCMV, HCV, RSV, and others, where myeloid cells influence the control and clearance of the virus from the host, as well as the severity and resolution of tissue damage, via the activities of iNOS and/or Arg1. Clearly, monocyte/macrophage activation and arginine metabolism will continue to be important areas of investigation in the context of viral infections.",2014 Sep 8,"['Burrack, Kristina S.', 'Morrison, Thomas E.']",Front Immunol,,,True
e49106784cd05d905c10780cc5dbe2a10a6badb7,PMC,Correction: Infection with MERS-CoV Causes Lethal Pneumonia in the Common Marmoset,http://dx.doi.org/10.1371/journal.ppat.1004431,PMC4159343,,CC BY,,2014 Sep 9,,PLoS Pathog,,,True
8b369168263656b024f65707b9bb501d1b75a56e,PMC,Heterogeneous pathological outcomes after experimental pH1N1 influenza infection in ferrets correlate with viral replication and host immune responses in the lung,http://dx.doi.org/10.1186/s13567-014-0085-8,PMC4161856,25163545,CC BY,"The swine-origin pandemic (p) H1N1 influenza A virus causes mild upper-respiratory tract disease in most human patients. However, some patients developed severe lower-respiratory tract infections with fatal consequences, and the cause of these infections remain unknown. Recently, it has been suggested that different populations have different degrees of susceptibility to pH1N1 strains due to host genetic variations that are associated with inappropriate immune responses against viral genetic characteristics. Here, we tested whether the pathologic patterns of influenza strains that produce different disease outcomes in humans could be reproduced in a ferret model. Our results revealed that the severities of infection did not correspond to particular viral isolate and were not associated with the clinical phenotypes of the corresponding patients. Severe pathological outcomes were associated with higher viral replication, especially in alveolar areas, and with an exacerbated innate cellular immune response that was characterised by substantial phagocytic and cytotoxic cell migration into the lungs. Moreover, detrimental innate cellular responses were linked to the up-regulation of several proinflammatory cytokines and chemokines and the down-regulation of IFNα in the lungs. Additionally, severe lung lesions were associated with greater up-regulations of pro-apoptotic markers and higher levels of apoptotic neutrophils and macrophages. In conclusion, this study confirmed that the clinicopathological outcomes of pH1N1 infection in ferrets were not only due to viral replication abilities but also depended on the hosts’ capacities to mount efficient immune responses to control viral infection of the lung. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-014-0085-8) contains supplementary material, which is available to authorized users.",2014 Aug 28,"['Vidaña, Beatriz', 'Martínez, Jorge', 'Martínez-Orellana, Pamela', 'García Migura, Lourdes', 'Montoya, María', 'Martorell, Jaime', 'Majó, Natàlia']",Vet Res,,,True
44e1e81a18b18799c1ab86e439050fff057897d4,PMC,Progress and challenges of disaster health management in China: a scoping review,http://dx.doi.org/10.3402/gha.v7.24986,PMC4161949,25215910,CC BY,"BACKGROUND: Despite the importance of an effective health system response to various disasters, relevant research is still in its infancy, especially in middle- and low-income countries. OBJECTIVE: This paper provides an overview of the status of disaster health management in China, with its aim to promote the effectiveness of the health response for reducing disaster-related mortality and morbidity. DESIGN: A scoping review method was used to address the recent progress of and challenges to disaster health management in China. Major health electronic databases were searched to identify English and Chinese literature that were relevant to the research aims. RESULTS: The review found that since 2003 considerable progress has been achieved in the health disaster response system in China. However, there remain challenges that hinder effective health disaster responses, including low standards of disaster-resistant infrastructure safety, the lack of specific disaster plans, poor emergency coordination between hospitals, lack of portable diagnostic equipment and underdeveloped triage skills, surge capacity, and psychological interventions. Additional challenges include the fragmentation of the emergency health service system, a lack of specific legislation for emergencies, disparities in the distribution of funding, and inadequate cost-effective considerations for disaster rescue. CONCLUSIONS: One solution identified to address these challenges appears to be through corresponding policy strategies at multiple levels (e.g. community, hospital, and healthcare system level).",2014 Sep 10,"['Zhong, Shuang', 'Clark, Michele', 'Hou, Xiang-Yu', 'Zang, Yuli', 'FitzGerald, Gerard']",Glob Health Action,,,True
1a8daad89d2701b4cf603e668f6aab1209b6237e,PMC,Autoreactivity to Glucose Regulated Protein 78 Links Emphysema and Osteoporosis in Smokers,http://dx.doi.org/10.1371/journal.pone.0105066,PMC4162538,25216103,CC BY,"RATIONALE: Emphysema and osteoporosis are epidemiologically associated diseases of cigarette smokers. The causal mechanism(s) linking these illnesses is unknown. We hypothesized autoimmune responses may be involved in both disorders. OBJECTIVES: To discover an antigen-specific autoimmune response associated with both emphysema and osteoporosis among smokers. METHODS: Replicate nonbiased discovery assays indicated that autoimmunity to glucose regulated protein 78 (GRP78), an endoplasmic reticulum chaperone and cell surface signaling receptor, is present in many smokers. Subject assessments included spirometry, chest CT scans, dual x-ray absorptiometry, and immunoblots for anti-GRP78 IgG. Anti-GRP78 autoantibodies were isolated from patient plasma by affinity chromatography, leukocyte functions assessed by flow cytometry, and soluble metabolites and mediators measured by immunoassays. MEASUREMENTS AND MAIN RESULTS: Circulating anti-GRP78 IgG autoantibodies were detected in plasma specimens from 86 (32%) of the 265 smoking subjects. Anti-GRP78 autoantibodies were singularly prevalent among subjects with radiographic emphysema (OR 3.1, 95%CI 1.7–5.7, p = 0.003). Anti-GRP78 autoantibodies were also associated with osteoporosis (OR 4.7, 95%CI 1.7–13.3, p = 0.002), and increased circulating bone metabolites (p = 0.006). Among emphysematous subjects, GRP78 protein was an autoantigen of CD4 T-cells, stimulating lymphocyte proliferation (p = 0.0002) and IFN-gamma production (p = 0.03). Patient-derived anti-GRP78 autoantibodies had avidities for osteoclasts and macrophages, and increased macrophage NFkB phosphorylation (p = 0.005) and productions of IL-8, CCL-2, and MMP9 (p = 0.005, 0.007, 0.03, respectively). CONCLUSIONS: Humoral and cellular GRP78 autoimmune responses in smokers have numerous biologically-relevant pro-inflammatory and other deleterious actions, and are associated with emphysema and osteoporosis. These findings may have relevance for the pathogenesis of smoking-associated diseases, and development of biomarker immunoassays and/or novel treatments for these disorders.",2014 Sep 12,"['Bon, Jessica', 'Kahloon, Rehan', 'Zhang, Yingze', 'Xue, Jianmin', 'Fuhrman, Carl R.', 'Tan, Jiangning', 'Burger, Mathew', 'Kass, Daniel J.', 'Csizmadia, Eva', 'Otterbein, Leo', 'Chandra, Divay', 'Bhargava, Arpit', 'Pilewski, Joseph M.', 'Roodman, G. David', 'Sciurba, Frank C.', 'Duncan, Steven R.']",PLoS One,,,True
bff6e0b359144d2d7f0a1911dc76443c979690b7,PMC,"Isolation and characterization of 11 novel microsatellite loci in a West African leaf-nosed bat, Hipposideros aff. ruber",http://dx.doi.org/10.1186/1756-0500-7-607,PMC4162931,25189128,CC BY,"BACKGROUND: Noack’s leaf-nosed bat, Hipposideros ruber, is a cryptic species within the Hipposideros caffer species complex. Despite a widespread distribution in Africa and being host to potentially zoonotic viruses, the genetic structure and ecology of H. ruber is poorly known. Here we describe the development of 11 novel polymorphic microsatellite loci to facilitate the investigation of genetic structure. FINDINGS: We selected 20 microsatellite sequences identified from high throughput sequence reads and PCR amplified these for 38 individuals, yielding 11 consistently amplifying and scorable loci. The number of alleles per locus ranged from two to 12, and observed heterozygosities from 0.00 to 0.865. No evidence of linkage disequilibrium was observed, and nine of the markers showed no departure from Hardy-Weinberg equilibrium. We demonstrate successful amplification in two closely related species and two divergent lineages of the H. caffer species complex. CONCLUSIONS: These new markers will provide a valuable tool to investigate genetic structure in the poorly understood Hipposideros caffer species complex.",2014 Sep 4,"['Baldwin, Heather J', 'Vallo, Peter', 'Gardner, Michael G', 'Drosten, Christian', 'Tschapka, Marco', 'Stow, Adam J']",BMC Res Notes,,,True
482ceb8b002b0c3f8ec6f26fc0093dd90cec2b0c,PMC,Bioassay Directed Isolation and Biological Evaluation of Compounds Isolated from Rubus fairholmianus Gard.,http://dx.doi.org/10.1155/2014/204340,PMC4165380,25254204,CC BY,"The in vitro and in silico analysis of Rubus fairholmianus acetone extract for antioxidant, antiproliferative, and anti-inflammatory activity led to the isolation of six compounds. Amongst all the six isolated compounds tested, 1-(2-hydroxyphenyl)-4-methylpentan-1-one (compound 1) and 2-[(3-methylbutoxy) carbonyl] benzoic acid (compound 2) were found to be more active in inhibiting BRCA and COX target proteins, which also showed the better results for DPPH and ABTS radical scavenging assays. The promising results of this investigation emphasize the importance of using R. fairholmianus in the treatment of radical generated disorders mainly cancer and other inflammatory diseases.",2014 Sep 1,"['Plackal George, Blassan', 'Thangaraj, Parimelazhagan', 'Sulaiman, Cheruthazhakkatt', 'Piramanayagam, Shanmughavel', 'Ramaswamy, Sathish Kumar']",Biomed Res Int,,,True
2ab5a9cc48131a2a4fc4c2e8be6fabc68aa6397c,PMC,Predictors of Mortality in Mechanically Ventilated Critical Pertussis in a low Income Country,http://dx.doi.org/10.4084/MJHID.2014.059,PMC4165494,25237472,CC BY,"BACKGROUND: Critical pertussis is characterized by severe respiratory failure, important leukocytosis, pulmonary hypertension, septic shock and encephalopathy. AIM: To describe the clinical course of critical pertussis, and identify predictors of death at the time of presentation for medical care. METHODOLOGY: Retrospective study conducted in children’s hospital Tunisian PICU between 01 January and 31 October 2013. Patients with critical pertussis confirmed by RT-PCR and requiring mechanical ventilation were included. Predictors of death were studied. RESULTS: A total of 17 patients was studied. Median age was 50 days. Mortality was 23%. Predictors risk of mortality were : high PRISM score (Pediatric Risk of Mortality Score) (p=0,007), shock (p=0,002), tachycardia (p=0,005), seizures (p=0,006), altered mental status (p=0,006), elevated WBC count (p=0,003) and hemodynamic support (p=0022). However, the difference did not reach statistical significance in comorbidity, pneumoniae, high pulmonary hypertension or exchange transfusion. Concomitant viral or bacterial co-infection was not related to poor outcome. CONCLUSION: Young infants are at high risk to have critical pertussis. Despite advances in life support and the treatment of organ failure in childhood critical illness, critical pertussis remains difficult to treat.",2014 Sep 1,"['Borgi, Aida', 'Menif, Khaled', 'Belhadj, Sarra', 'Ghali, Narjess', 'Salmen, Loukil', 'Hamdi, Asma', 'Khaldi, Ammar', 'Bouaffsoun, Aida', 'Kechaou, Sonia', 'Kechrid, Amel', 'Bouziri, Asma', 'Benjaballah, Nejla']",Mediterr J Hematol Infect Dis,,,True
9fc349caa11e13a92c959d5f8b1669f4b425e2d2,PMC,Autophagic effects of Chaihu (dried roots of Bupleurum Chinense DC or Bupleurum scorzoneraefolium WILD),http://dx.doi.org/10.1186/1749-8546-9-21,PMC4165614,25228909,CC BY,"Chaihu, prepared from the dried roots of Bupleurum Chinense DC (also known as bei Chaihu in Chinese) or Bupleurum scorzoneraefolium WILD (also known as nan Chaihu in Chinese), is a herbal medicine for harmonizing and soothing gan (liver) qi stagnation. Substantial pharmacological studies have been conducted on Chaihu and its active components (saikosaponins). One of the active components of Chaihu, saikosaponin-d, exhibited anticancer effects via autophagy induction. This article reviews the pharmacological findings for the roles of autophagy in the pharmacological actions of Chaihu and saikosaponins.",2014 Sep 11,"['Law, Betty Yuen-Kwan', 'Mo, Jing-Fang', 'Wong, Vincent Kam-Wai']",Chin Med,,,True
d0bb873b6eb934aefa7743cd2fb095c7e3318410,PMC,Dendritic Cells from Aged Subjects Display Enhanced Inflammatory Responses to Chlamydophila pneumoniae,http://dx.doi.org/10.1155/2014/436438,PMC4165882,25253920,CC BY,"Chlamydophila pneumoniae (CPn) is a common respiratory pathogen that causes a chronic and persistent airway infection. The elderly display an increased susceptibility and severity to this infection. However, the underlying mechanisms are not well understood. Dendritic cells (DCs) are the initiators and regulators of immune responses. Therefore, we investigated the role of DCs in the age-associated increased CPn infection in vitro in humans. Though the expression of activation markers was comparable between the two age groups, DCs from aged subjects secreted enhanced levels of proinflammatory mediators such as TNF-α and CXCL-10 in response to CPn. In contrast, the secretion of IL-10 and innate interferons, IFN-α and IFN-λ, was severely impaired in DCs from aged donors. The increased activation of DCs from aged subjects to CPn also resulted in enhanced proliferation of CD4 and CD8 T cells in a DC-T coculture. Furthermore, T cells primed with CPn-stimulated DCs from aged subjects secreted increased levels of IFN-γ and reduced levels of IL-10 compared to DCs obtained from young subjects. In summary, DCs from the elderly displayed enhanced inflammatory response to CPn which may result in airway remodeling and increase the susceptibility of the elderly to respiratory diseases such as asthma.",2014 Sep 1,"['Prakash, Sangeetha', 'Agrawal, Sudhanshu', 'Ma, Dandan', 'Gupta, Sudhir', 'Peterson, Ellena M.', 'Agrawal, Anshu']",Mediators Inflamm,,,False
a7bb5432ed9fc93c11b893bd499bb66becfc71f6,PMC,Dendritic Cells from Aged Subjects Display Enhanced Inflammatory Responses to Chlamydophila pneumoniae,http://dx.doi.org/10.1155/2014/436438,PMC4165882,25253920,CC BY,"Chlamydophila pneumoniae (CPn) is a common respiratory pathogen that causes a chronic and persistent airway infection. The elderly display an increased susceptibility and severity to this infection. However, the underlying mechanisms are not well understood. Dendritic cells (DCs) are the initiators and regulators of immune responses. Therefore, we investigated the role of DCs in the age-associated increased CPn infection in vitro in humans. Though the expression of activation markers was comparable between the two age groups, DCs from aged subjects secreted enhanced levels of proinflammatory mediators such as TNF-α and CXCL-10 in response to CPn. In contrast, the secretion of IL-10 and innate interferons, IFN-α and IFN-λ, was severely impaired in DCs from aged donors. The increased activation of DCs from aged subjects to CPn also resulted in enhanced proliferation of CD4 and CD8 T cells in a DC-T coculture. Furthermore, T cells primed with CPn-stimulated DCs from aged subjects secreted increased levels of IFN-γ and reduced levels of IL-10 compared to DCs obtained from young subjects. In summary, DCs from the elderly displayed enhanced inflammatory response to CPn which may result in airway remodeling and increase the susceptibility of the elderly to respiratory diseases such as asthma.",2014 Sep 1,"['Prakash, Sangeetha', 'Agrawal, Sudhanshu', 'Ma, Dandan', 'Gupta, Sudhir', 'Peterson, Ellena M.', 'Agrawal, Anshu']",Mediators Inflamm,,,True
d1ecd2ec6f1030c8e1ba1844e0fea59b19267a55,PMC,Global health diplomacy: advancing foreign policy and global health interests,http://dx.doi.org/10.9745/GHSP-D-12-00048,PMC4168555,25276514,CC BY,"Attention to global health diplomacy has been rising but the future holds challenges, including a difficult budgetary environment. Going forward, both global health and foreign policy practitioners would benefit from working more closely together to achieve greater mutual understanding and to advance respective mutual goals.",2013 Mar 21,"['Michaud, Josh', 'Kates, Jennifer']",Glob Health Sci Pract,,,True
12cbf7162f5525c020e909c85db4142007c64603,PMC,"Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications",http://dx.doi.org/10.3762/bjoc.10.200,PMC4168895,25246951,CC BY,"(1H-Benzo[d][1,2,3]triazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), 1H-benzo[d][1,2,3]triazol-1-yl 4-methylbenzenesulfonate (Bt-OTs), and 3H-[1,2,3]triazolo[4,5-b]pyridine-3-yl 4-methylbenzenesulfonate (At-OTs) are classically utilized in peptide synthesis for amide-bond formation. However, a previously undescribed reaction of these compounds with alcohols in the presence of a base, leads to 1-alkoxy-1H-benzo- (Bt-OR) and 7-azabenzotriazoles (At-OR). Although BOP undergoes reactions with alcohols to furnish 1-alkoxy-1H-benzotriazoles, Bt-OTs proved to be superior. Both, primary and secondary alcohols undergo reaction under generally mild reaction conditions. Correspondingly, 1-alkoxy-1H-7-azabenzotriazoles were synthesized from At-OTs. Mechanistically, there are three pathways by which these peptide-coupling agents can react with alcohols. From (31)P{(1)H}, [(18)O]-labeling, and other chemical experiments, phosphonium and tosylate derivatives of alcohols seem to be intermediates. These then react with BtO(−) and AtO(−) produced in situ. In order to demonstrate broader utility, this novel reaction has been used to prepare a series of acyclic nucleoside-like compounds. Because BtO(−) is a nucleofuge, several Bt-OCH(2)Ar substrates have been evaluated in nucleophilic substitution reactions. Finally, the possible formation of Pd π–allyl complexes by departure of BtO(−) has been queried. Thus, alpha-allylation of three cyclic ketones was evaluated with 1-(cinnamyloxy)-1H-benzo[d][1,2,3]triazole, via in situ formation of pyrrolidine enamines and Pd catalysis.",2014 Aug 19,"['Lakshman, Mahesh K', 'Singh, Manish K', 'Kumar, Mukesh', 'Chamala, Raghu Ram', 'Yedulla, Vijayender R', 'Wagner, Domenick', 'Leung, Evan', 'Yang, Lijia', 'Matin, Asha', 'Ahmad, Sadia']",Beilstein J Org Chem,,,True
c33d7d8d49ed2a2ea4c997f587e75b9723418226,PMC,"Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications",http://dx.doi.org/10.3762/bjoc.10.200,PMC4168895,25246951,CC BY,"(1H-Benzo[d][1,2,3]triazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), 1H-benzo[d][1,2,3]triazol-1-yl 4-methylbenzenesulfonate (Bt-OTs), and 3H-[1,2,3]triazolo[4,5-b]pyridine-3-yl 4-methylbenzenesulfonate (At-OTs) are classically utilized in peptide synthesis for amide-bond formation. However, a previously undescribed reaction of these compounds with alcohols in the presence of a base, leads to 1-alkoxy-1H-benzo- (Bt-OR) and 7-azabenzotriazoles (At-OR). Although BOP undergoes reactions with alcohols to furnish 1-alkoxy-1H-benzotriazoles, Bt-OTs proved to be superior. Both, primary and secondary alcohols undergo reaction under generally mild reaction conditions. Correspondingly, 1-alkoxy-1H-7-azabenzotriazoles were synthesized from At-OTs. Mechanistically, there are three pathways by which these peptide-coupling agents can react with alcohols. From (31)P{(1)H}, [(18)O]-labeling, and other chemical experiments, phosphonium and tosylate derivatives of alcohols seem to be intermediates. These then react with BtO(−) and AtO(−) produced in situ. In order to demonstrate broader utility, this novel reaction has been used to prepare a series of acyclic nucleoside-like compounds. Because BtO(−) is a nucleofuge, several Bt-OCH(2)Ar substrates have been evaluated in nucleophilic substitution reactions. Finally, the possible formation of Pd π–allyl complexes by departure of BtO(−) has been queried. Thus, alpha-allylation of three cyclic ketones was evaluated with 1-(cinnamyloxy)-1H-benzo[d][1,2,3]triazole, via in situ formation of pyrrolidine enamines and Pd catalysis.",2014 Aug 19,"['Lakshman, Mahesh K', 'Singh, Manish K', 'Kumar, Mukesh', 'Chamala, Raghu Ram', 'Yedulla, Vijayender R', 'Wagner, Domenick', 'Leung, Evan', 'Yang, Lijia', 'Matin, Asha', 'Ahmad, Sadia']",Beilstein J Org Chem,,,True
4141cdba2be695f11c3f7278d72481ae521eebd9,PMC,"Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications",http://dx.doi.org/10.3762/bjoc.10.200,PMC4168895,25246951,CC BY,"(1H-Benzo[d][1,2,3]triazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), 1H-benzo[d][1,2,3]triazol-1-yl 4-methylbenzenesulfonate (Bt-OTs), and 3H-[1,2,3]triazolo[4,5-b]pyridine-3-yl 4-methylbenzenesulfonate (At-OTs) are classically utilized in peptide synthesis for amide-bond formation. However, a previously undescribed reaction of these compounds with alcohols in the presence of a base, leads to 1-alkoxy-1H-benzo- (Bt-OR) and 7-azabenzotriazoles (At-OR). Although BOP undergoes reactions with alcohols to furnish 1-alkoxy-1H-benzotriazoles, Bt-OTs proved to be superior. Both, primary and secondary alcohols undergo reaction under generally mild reaction conditions. Correspondingly, 1-alkoxy-1H-7-azabenzotriazoles were synthesized from At-OTs. Mechanistically, there are three pathways by which these peptide-coupling agents can react with alcohols. From (31)P{(1)H}, [(18)O]-labeling, and other chemical experiments, phosphonium and tosylate derivatives of alcohols seem to be intermediates. These then react with BtO(−) and AtO(−) produced in situ. In order to demonstrate broader utility, this novel reaction has been used to prepare a series of acyclic nucleoside-like compounds. Because BtO(−) is a nucleofuge, several Bt-OCH(2)Ar substrates have been evaluated in nucleophilic substitution reactions. Finally, the possible formation of Pd π–allyl complexes by departure of BtO(−) has been queried. Thus, alpha-allylation of three cyclic ketones was evaluated with 1-(cinnamyloxy)-1H-benzo[d][1,2,3]triazole, via in situ formation of pyrrolidine enamines and Pd catalysis.",2014 Aug 19,"['Lakshman, Mahesh K', 'Singh, Manish K', 'Kumar, Mukesh', 'Chamala, Raghu Ram', 'Yedulla, Vijayender R', 'Wagner, Domenick', 'Leung, Evan', 'Yang, Lijia', 'Matin, Asha', 'Ahmad, Sadia']",Beilstein J Org Chem,,,True
e24bf8c23979d56fff33bd4ed96fb00a117f701b,PMC,A New Approach for Monitoring Ebolavirus in Wild Great Apes,http://dx.doi.org/10.1371/journal.pntd.0003143,PMC4169258,25232832,CC0,"BACKGROUND: Central Africa is a “hotspot” for emerging infectious diseases (EIDs) of global and local importance, and a current outbreak of ebolavirus is affecting multiple countries simultaneously. Ebolavirus is suspected to have caused recent declines in resident great apes. While ebolavirus vaccines have been proposed as an intervention to protect apes, their effectiveness would be improved if we could diagnostically confirm Ebola virus disease (EVD) as the cause of die-offs, establish ebolavirus geographical distribution, identify immunologically naïve populations, and determine whether apes survive virus exposure. METHODOLOGY/PRINCIPAL FINDINGS: Here we report the first successful noninvasive detection of antibodies against Ebola virus (EBOV) from wild ape feces. Using this method, we have been able to identify gorillas with antibodies to EBOV with an overall prevalence rate reaching 10% on average, demonstrating that EBOV exposure or infection is not uniformly lethal in this species. Furthermore, evidence of antibodies was identified in gorillas thought previously to be unexposed to EBOV (protected from exposure by rivers as topological barriers of transmission). CONCLUSIONS/SIGNIFICANCE: Our new approach will contribute to a strategy to protect apes from future EBOV infections by early detection of increased incidence of exposure, by identifying immunologically naïve at-risk populations as potential targets for vaccination, and by providing a means to track vaccine efficacy if such intervention is deemed appropriate. Finally, since human EVD is linked to contact with infected wildlife carcasses, efforts aimed at identifying great ape outbreaks could have a profound impact on public health in local communities, where EBOV causes case-fatality rates of up to 88%.",2014 Sep 18,"['Reed, Patricia E.', 'Mulangu, Sabue', 'Cameron, Kenneth N.', 'Ondzie, Alain U.', 'Joly, Damien', 'Bermejo, Magdalena', 'Rouquet, Pierre', 'Fabozzi, Giulia', 'Bailey, Michael', 'Shen, Zhimin', 'Keele, Brandon F.', 'Hahn, Beatrice', 'Karesh, William B.', 'Sullivan, Nancy J.']",PLoS Negl Trop Dis,,,True
95e8817d39f27e9ae56bf7b2bb8f4f8bf3c9dd19,PMC,A New Approach for Monitoring Ebolavirus in Wild Great Apes,http://dx.doi.org/10.1371/journal.pntd.0003143,PMC4169258,25232832,CC0,"BACKGROUND: Central Africa is a “hotspot” for emerging infectious diseases (EIDs) of global and local importance, and a current outbreak of ebolavirus is affecting multiple countries simultaneously. Ebolavirus is suspected to have caused recent declines in resident great apes. While ebolavirus vaccines have been proposed as an intervention to protect apes, their effectiveness would be improved if we could diagnostically confirm Ebola virus disease (EVD) as the cause of die-offs, establish ebolavirus geographical distribution, identify immunologically naïve populations, and determine whether apes survive virus exposure. METHODOLOGY/PRINCIPAL FINDINGS: Here we report the first successful noninvasive detection of antibodies against Ebola virus (EBOV) from wild ape feces. Using this method, we have been able to identify gorillas with antibodies to EBOV with an overall prevalence rate reaching 10% on average, demonstrating that EBOV exposure or infection is not uniformly lethal in this species. Furthermore, evidence of antibodies was identified in gorillas thought previously to be unexposed to EBOV (protected from exposure by rivers as topological barriers of transmission). CONCLUSIONS/SIGNIFICANCE: Our new approach will contribute to a strategy to protect apes from future EBOV infections by early detection of increased incidence of exposure, by identifying immunologically naïve at-risk populations as potential targets for vaccination, and by providing a means to track vaccine efficacy if such intervention is deemed appropriate. Finally, since human EVD is linked to contact with infected wildlife carcasses, efforts aimed at identifying great ape outbreaks could have a profound impact on public health in local communities, where EBOV causes case-fatality rates of up to 88%.",2014 Sep 18,"['Reed, Patricia E.', 'Mulangu, Sabue', 'Cameron, Kenneth N.', 'Ondzie, Alain U.', 'Joly, Damien', 'Bermejo, Magdalena', 'Rouquet, Pierre', 'Fabozzi, Giulia', 'Bailey, Michael', 'Shen, Zhimin', 'Keele, Brandon F.', 'Hahn, Beatrice', 'Karesh, William B.', 'Sullivan, Nancy J.']",PLoS Negl Trop Dis,,,False
0fb7458693f388bce5927bb1f9be866eb36b6349,PMC,Association of Cytokines in Individuals Sensitive and Insensitive to Dust Mites in a Brazilian Population,http://dx.doi.org/10.1371/journal.pone.0107921,PMC4169580,25238536,CC BY,"INTRODUCTION: Allergic reaction to dust mites is a relatively common condition among children, triggering cutaneous and respiratory responses that have a great impact on the health of this population. Anaphylactic hypersensitivity is characterized by an exacerbated response involving the production of regulatory cytokines responsible for stimulating the production of IgE antibodies. OBJECTIVE: To investigate an association of variants in cytokine genes (IL1A (−889), IL1B (−511, +3962), IL1R (1970), IL1RA (11100), IL4RA (+1902), IL12 (−1188), IFNG (+874), TGFB1 (codon 10, codon 25), TNFA (−308, −238), IL2 (−330, +166), IL4 (−1098, −590, −33), IL6 (−174, nt565), and IL10 (−1082, −819, −592)) between patients sensitive to dust mites and a control group. METHODS: A total of 254 patients were grouped as atopic and non-atopic according to sensitivity as evaluated by the Prick Test and to cytokine genotyping by the polymerase chain reaction-sequence specific primers (PCR-SSP) method using the Cytokine Genotyping Kit. RESULTS: A comparison between individuals allergic to Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Blomia tropicalis and a non-atopic control group showed significant differences between allele and genotype frequencies in the regulatory regions of cytokine genes, with important evidence for IL4 (−590) in T/C (10.2% vs. 43.1%, odd ratio [OR] = 0.15, p = 5.2 10(−8), pc = 0.0000011, and 95% confidence interval [95%CI] = 0.07–0.32) and T/T genotypes (42.9% vs. 13.8%, OR = 4.69, p = 2.5 10(−6), pc = 0.000055, and 95%CI = 2.42–9.09). Other associations were observed in the pro-inflammatory cytokines IL1A (−889) (T/T, C, and T) and IL2 (−330) (G/T and T/T) and the anti-inflammatory cytokines IL4RA (+1902) (A and G), IL4 (−590) (T/C, T/T, C, and T), and IL10 (−592) (A/A, C/A, A, and C). CONCLUSION: Our results suggest a possible association between single nucleotide polymorphisms (SNPs) in cytokine genes and hypersensitivity to dust mites.",2014 Sep 19,"['Caniatti, Marcela Caleffi da Costa Lima', 'Marchioro, Ariella Andrade', 'Guilherme, Ana Lúcia Falavigna', 'Tsuneto, Luiza Tamie']",PLoS One,,,True
f33e644d058bc8373378c115878be06346298687,PMC,"Docetaxel induces moderate ovarian toxicity in mice, primarily affecting granulosa cells of early growing follicles",http://dx.doi.org/10.1093/molehr/gau057,PMC4172173,25080441,CC BY,"Advances in cancer therapy have focused attention on the quality of life of cancer survivors. Since infertility is a major concern following chemotherapy, it is important to characterize the drug-specific damage to the reproductive system to help find appropriate protective strategies. This study investigates the damage on neonatal mouse ovary maintained in vitro for 6 days, and exposed for 24 h (on Day 2) to clinically relevant doses of Docetaxel (DOC; low: 0.1 µM, mid: 1 µM, high: 10 µM). Furthermore, the study explores the putative protective action exerted by Tri-iodothyronine (T3; 10(−7) M). At the end of culture, morphological analyses and follicle counts showed that DOC negatively impacts on early growing follicles, decreasing primary follicle number and severely affecting health at the transitional and primary stages. Poor follicle health was mainly due to effects on granulosa cells, indicating that the effects of DOC on oocytes were likely to be secondary to granulosa cell damage. DOC damages growing follicles specifically, with no direct effect on the primordial follicle reserve. Immunostaining and western blotting showed that DOC induces activation of intrinsic, type II apoptosis in ovarian somatic cells; increasing the levels of cleaved caspase 3, cleaved caspase 8, Bax and cleaved poly(ADP-ribose) polymerase, while also inducing movement of cytochrome C from mitochondria into the cytosol. T3 did not prevent the damage induced by the low dose of DOC. These results demonstrated that DOC induces a gonadotoxic effect on the mouse ovary through induction of somatic cell apoptosis, with no evidence of direct effects on the oocyte, and that the damaging effect is not mitigated by T3.",2014 Oct 30,"['Lopes, Federica', 'Smith, Rowena', 'Anderson, Richard A.', 'Spears, Norah']",Mol Hum Reprod,,,True
7c1b1700315cc018b94e1488667365315137cb20,PMC,Rapid and sensitive detection of canine distemper virus by one-tube reverse transcription-insulated isothermal polymerase chain reaction,http://dx.doi.org/10.1186/s12917-014-0213-8,PMC4172905,25200113,CC BY,"BACKGROUND: Canine distemper virus (CDV) has been associated with outbreaks of canine infectious respiratory disease in shelters and boarding kennel environments. POCKIT(TM) Nucleic Acid Analyzer is a field-deployable device capable of generating automatically interpreted insulated isothermal polymerase chain reaction (iiPCR) results from extracted nucleic acid within one hour. In this study, reverse transcription iiPCR (RT-iiPCR) was developed to facilitate point-of-need diagnosis of CDV infection. RESULTS: Analytical sensitivity (limit of detection 95%) of the established CDV RT-iiPCR was about 11 copies of in vitro transcribed RNA per reaction. CDV RT-iiPCR generated positive signals from CDV, but not Bordetella bronchiseptica, canine parvovirus, canine herpesvirus, canine adenovirus 2, canine influenza virus (subtype H3N8), canine parainfluenza virus, and canine respiratory coronavirus. To evaluate accuracy of the established reaction in canine distemper clinical diagnosis, 110 specimens from dogs, raccoons, and foxes suspected with CDV infection were tested simultaneously by CDV RT-iiPCR and real-time RT-PCR. CDV RT-iiPCR demonstrated excellent sensitivity (100%) and specificity (100%), compared to real-time RT-PCR. CONCLUSIONS: The results indicated an excellent correlation between RT-iiPCR and a reference real time RT-PCR method. Working in a lyophilized format, the established method has great potential to be used for point-of-care diagnosis of canine distemper in animals, especially in resource-limited facilities.",2014 Sep 9,"['Wilkes, Rebecca P', 'Tsai, Yun-Long', 'Lee, Pei-Yu', 'Lee, Fu-Chun', 'Chang, Hsiao-Fen Grace', 'Wang, Hwa-Tang Thomas']",BMC Vet Res,,,True
468c549a9b35a3f23be71f098c3ab910abadac8d,PMC,"Management of the slowly emerging zoonosis, Hendra virus, by private veterinarians in Queensland, Australia: a qualitative study",http://dx.doi.org/10.1186/s12917-014-0215-6,PMC4173005,25224910,CC BY,"BACKGROUND: Veterinary infection control for the management of Hendra virus (HeV), an emerging zoonosis in Australia, remained suboptimal until 2010 despite 71.4% (5/7) of humans infected with HeV being veterinary personnel or assisting a veterinarian, three of whom died before 2009. The aim of this study was to identify the perceived barriers to veterinary infection control and HeV management in private veterinary practice in Queensland, where the majority of HeV outbreaks have occurred in Australia. RESULTS: Most participants agreed that a number of key factors had contributed to the slow uptake of adequate infection control measures for the management of HeV amongst private veterinarians: a work culture characterised by suboptimal infection control standards and misconceptions about zoonotic risks; a lack of leadership and support from government authorities; the difficulties of managing biosecurity and public health issues from a private workforce perspective; and the slow pattern of emergence of HeV. By 2010, some infection control and HeV management changes had been implemented. Participants interviewed agreed that further improvements remained necessary; but also cautioned that this was a complex process which would require time. CONCLUSION: Private veterinarians and government authorities prior to 2009 were unprepared to handle new slowly emerging zoonoses, which may explain their mismanagement of HeV. Slowly emerging zoonoses may be of low public health significance but of high significance for specialised groups such as veterinarians. Private veterinarians, who are expected to fulfil an active biosecurity and public health role in the frontline management of such emerging zoonoses, need government agencies to better recognise their contribution, to consult with the veterinary profession when devising guidelines for the management of zoonoses and to provide them with greater leadership and support. We propose that specific infection control guidelines for the management of slowly emerging zoonoses in private veterinary settings need to be developed.",2014 Sep 17,"['Mendez, Diana H', 'Kelly, Jenny', 'Buttner, Petra', 'Nowak, Madeleine', 'Speare, Rick']",BMC Vet Res,,,True
3dede13dfa857e159c3fd7830374e1dc76008f2e,PMC,A novel porcine reproductive and respiratory syndrome virus vector system that stably expresses enhanced green fluorescent protein as a separate transcription unit,http://dx.doi.org/10.1186/1297-9716-44-104,PMC4176086,24176053,CC BY,"Here we report the rescue of a recombinant porcine reproductive and respiratory syndrome virus (PRRSV) carrying an enhanced green fluorescent protein (EGFP) reporter gene as a separate transcription unit. A copy of the transcription regulatory sequence for ORF6 (TRS6) was inserted between the N protein and 3′-UTR to drive the transcription of the EGFP gene and yield a general purpose expression vector. Successful recovery of PRRSV was obtained using an RNA polymerase II promoter to drive transcription of the full-length virus genome, which was assembled in a bacterial artificial chromosome (BAC). The recombinant virus showed growth replication characteristics similar to those of the wild-type virus in the infected cells. In addition, the recombinant virus stably expressed EGFP for at least 10 passages. EGFP expression was detected at approximately 10 h post infection by live-cell imaging to follow the virus spread in real time and the infection of neighbouring cells occurred predominantly through cell-to-cell-contact. Finally, the recombinant virus generated was found to be an excellent tool for neutralising antibodies and antiviral compound screening. The newly established reverse genetics system for PRRSV could be a useful tool not only to monitor virus spread and screen for neutralising antibodies and antiviral compounds, but also for fundamental research on the biology of the virus.",2013 Oct 31,"['Wang, Chengbao', 'Huang, Baicheng', 'Kong, Ning', 'Li, Qiongyi', 'Ma, Yuping', 'Li, Zhijun', 'Gao, Jiming', 'Zhang, Chong', 'Wang, Xiangpeng', 'Liang, Chao', 'Dang, Lu', 'Xiao, Shuqi', 'Mu, Yang', 'Zhao, Qin', 'Sun, Yani', 'Almazan, Fernando', 'Enjuanes, Luis', 'Zhou, En-Min']",Vet Res,,,True
9ac01047c360e0def0d96adf2e59f6e5bd68b3b7,PMC,Photodynamic Antimicrobial Polymers for Infection Control,http://dx.doi.org/10.1371/journal.pone.0108500,PMC4177408,25250740,CC BY,"Hospital-acquired infections pose both a major risk to patient wellbeing and an economic burden on global healthcare systems, with the problem compounded by the emergence of multidrug resistant and biocide tolerant bacterial pathogens. Many inanimate surfaces can act as a reservoir for infection, and adequate disinfection is difficult to achieve and requires direct intervention. In this study we demonstrate the preparation and performance of materials with inherent photodynamic, surface-active, persistent antimicrobial properties through the incorporation of photosensitizers into high density poly(ethylene) (HDPE) using hot-melt extrusion, which require no external intervention except a source of visible light. Our aim is to prevent bacterial adherence to these surfaces and eliminate them as reservoirs of nosocomial pathogens, thus presenting a valuable advance in infection control. A two-layer system with one layer comprising photosensitizer-incorporated HDPE, and one layer comprising HDPE alone is also described to demonstrate the versatility of our approach. The photosensitizer-incorporated materials are capable of reducing the adherence of viable bacteria by up to 3.62 Log colony forming units (CFU) per square centimeter of material surface for methicillin resistant Staphylococcus aureus (MRSA), and by up to 1.51 Log CFU/cm(2) for Escherichia coli. Potential applications for the technology are in antimicrobial coatings for, or materials comprising objects, such as tubing, collection bags, handrails, finger-plates on hospital doors, or medical equipment found in the healthcare setting.",2014 Sep 24,"['McCoy, Colin P.', 'O’Neil, Edward J.', 'Cowley, John F.', 'Carson, Louise', 'De Baróid, Áine T.', 'Gdowski, Greg T.', 'Gorman, Sean P.', 'Jones, David S.']",PLoS One,,,True
b5a7acc938d3d05c5ef67cb6b1dd090805e487e5,PMC,Roles of the antioxidant properties of icariin and its phosphorylated derivative in the protection against duck virus hepatitis,http://dx.doi.org/10.1186/s12917-014-0226-3,PMC4177705,25244948,CC BY,"BACKGROUND: Duck viral hepatitis (DVH) is an acute disease of young ducklings with few convenient and effective veterinary drugs to treat. In pathology, present study mainly focused on the immune mechanism, but very few studies have concerned with the role of oxidative stress in the pathogenesis of DVH. To study the antioxidative and hepatoprotective effects of icariin and its phosphorylated derivative against DVH, we prepared phosphorylated icariin (p-icariin) using the sodium trimetaphosphate–sodium tripolyphosphate method. Ducklings were drunk with icariin and p-icariin after being challenged with duck hepatitis virus 1 (DHV-1). We recorded the number of dead ducklings, gross pathological changes in the liver, and changes in indices of oxidative stress and liver injury. The correlations between these indices were also analyzed. RESULTS: Exposure to DHV-1 induced significant oxidative damage in ducklings. Administration of icariin or p-icariin attenuated liver pathological injury and significantly increased the survival rate, with better outcomes in ducklings treated with p-icariin than in those treated with icariin. Icariin and p-icariin also attenuated the changes in oxidative stress and liver injury. We found positive correlations among indices of oxidative stress (malondialdehyde and inducible nitric oxide synthase) and liver injury (alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase), suggesting that DHV-1 causes significant oxidative damage, which is related to the extent of hepatic injury. CONCLUSIONS: Icariin and p-icariin improved the survival and attenuated oxidative stress and liver dysfunction induced by DHV-1. These outcomes were better in ducklings treated with p-icariin than in those treated by icariin. The clinical effects of both components were related to their antioxidant activities.",2014 Sep 24,"['Xiong, Wen', 'Chen, Yun', 'Wang, Yu', 'Liu, Jiaguo']",BMC Vet Res,,,True
a825eb21bd4ff17296f2f289faa849d326472b73,PMC,Hospital-based influenza morbidity and mortality surveillance system for influenza-like illnesses: a comparison with national influenza surveillance systems,http://dx.doi.org/10.1111/irv.12175,PMC4177793,24020512,CC BY,"The Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system is an emergency room (ER)-based influenza surveillance system in Korea that was established in 2011. The system was established under the assumption that integrated clinical and virologic surveillance could be performed rapidly and easily at seven tertiary hospitals' ER. Here, we assessed the correlation between data generated from the HIMM surveillance system and the Korean national influenza surveillance systems during the 2011–2012 influenza season using cross-correlation analysis and found strong correlations. Rapid antigen-test-based HIMM surveillance would predict the start of influenza epidemic earlier than pre-existing influenza-like-illness-based surveillance.",2014 Jan 11,"['Seo, Yu Bin', 'Song, Joon Young', 'Cheong, Hee Jin', 'Cho, Young Duck', 'Wie, Seong-Heon', 'Jeong, Hye Won', 'Kim, Woo Joo']",Influenza Other Respir Viruses,,,True
d4f6cfb312bae60aa35168d4a775bdb90c4bc39c,PMC,Respiratory viral infections and effects of meteorological parameters and air pollution in adults with respiratory symptoms admitted to the emergency room,http://dx.doi.org/10.1111/irv.12158,PMC4177797,24034701,CC BY,"BACKGROUND: Respiratory viral infections (RVIs) are the most common causes of respiratory infections. The prevalence of respiratory viruses in adults is underestimated. Meteorological variations and air pollution are likely to play a role in these infections. OBJECTIVES: The objectives of this study were to determine the number of emergency visits for influenza-like illness (ILI) and severe acute respiratory infection (SARI) and to evaluate the association between ILI/SARI, RVI prevalence, and meteorological factors/air pollution, in the city of Porto Alegre, Brazil, from November 2008 to October 2010. METHODS: Eleven thousand nine hundred and fifty-three hospitalizations (adults and children) for respiratory symptoms were correlated with meteorological parameters and air pollutants. In a subset of adults, nasopharyngeal aspirates were collected and analyzed through IFI test. The data were analyzed using time-series analysis. RESULTS: Influenza-like illness and SARI were diagnosed in 3698 (30·9%) and 2063 (17·7%) patients, respectively. Thirty-seven (9·0%) samples were positive by IFI and 93 of 410 (22·7%) were IFI and/or PCR positive. In a multivariate logistic regression model, IFI positivity was statistically associated with absolute humidity, use of air conditioning, and presence of mold in home. Sunshine duration was significantly associated with the frequency of ILI cases. For SARI cases, the variables mean temperature, sunshine duration, relative humidity, and mean concentration of pollutants were singnificant. CONCLUSIONS: At least 22% of infections in adult patients admitted to ER with respiratory complaints were caused by RVI. The correlations among meteorological variables, air pollution, ILI/SARI cases, and respiratory viruses demonstrated the relevance of climate factors as significant underlying contributors to the prevalence of RVI.",2014 Jan 26,"['Silva, Denise R', 'Viana, Vinícius P', 'Müller, Alice M', 'Livi, Fernando P', 'Dalcin, Paulo de Tarso R']",Influenza Other Respir Viruses,,,True
5300635b9c02f28ee26a26ee5547b6bc16cd0139,PMC,Increased cytokine/chemokines in serum from asthmatic and non-asthmatic patients with viral respiratory infection,http://dx.doi.org/10.1111/irv.12155,PMC4177805,23962134,CC BY,"BACKGROUND: Respiratory viral infections can induce different cytokine/chemokine profiles in lung tissues and have a significant influence on patients with asthma. There is little information about the systemic cytokine status in viral respiratory-infected asthmatic patients compared with non-asthmatic patients. OBJECTIVES: The aim of this study was to determine changes in circulating cytokines (IL-1β, TNF-α, IL-4, IL-5) and chemokines (MCP1: monocyte chemoattractant protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in patients with an asthmatic versus a non-asthmatic background with respiratory syncytial virus, parainfluenza virus or adenovirus respiratory infection. In addition, human monocyte cultures were incubated with respiratory viruses to determine the cytokine/chemokine profiles. PATIENTS/METHODS: Patients with asthmatic (n = 34) and non-asthmatic (n = 18) history and respiratory infections with respiratory syncytial virus, parainfluenza, and adenovirus were studied. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in blood and culture supernatants was determined by ELISA. Monocytes were isolated by Hystopaque gradient and cocultured with each of the above-mentioned viruses. RESULTS: Similar increased cytokine concentrations were observed in asthmatic and non-asthmatic patients. However, higher concentrations of chemokines were observed in asthmatic patients. Virus-infected monocyte cultures showed similar cytokine/chemokine profiles to those observed in the patients. CONCLUSIONS: Circulating cytokine profiles induced by acute viral lung infection were not related to asthmatic status, except for chemokines that were already increased in the asthmatic status. Monocytes could play an important role in the increased circulating concentration of cytokines found during respiratory viral infections.",2014 Jan 21,"['Giuffrida, María J', 'Valero, Nereida', 'Mosquera, Jesús', 'Alvarez de Mon, Melchor', 'Chacín, Betulio', 'Espina, Luz Marina', 'Gotera, Jennifer', 'Bermudez, John', 'Mavarez, Alibeth']",Influenza Other Respir Viruses,,,True
590dc551804c7579ac9623ee64f81d1186261faa,PMC,Reorganization of the Endosomal System in Salmonella-Infected Cells: The Ultrastructure of Salmonella-Induced Tubular Compartments,http://dx.doi.org/10.1371/journal.ppat.1004374,PMC4177991,25254663,CC BY,"During the intracellular life of Salmonella enterica, a unique membrane-bound compartment termed Salmonella-containing vacuole, or SCV, is formed. By means of translocated effector proteins, intracellular Salmonella also induce the formation of extensive, highly dynamic membrane tubules termed Salmonella-induced filaments or SIF. Here we report the first detailed ultrastructural analyses of the SCV and SIF by electron microscopy (EM), EM tomography and live cell correlative light and electron microscopy (CLEM). We found that a subset of SIF is composed of double membranes that enclose portions of host cell cytosol and cytoskeletal filaments within its inner lumen. Despite some morphological similarities, we found that the formation of SIF double membranes is independent from autophagy and requires the function of the effector proteins SseF and SseG. The lumen of SIF network is accessible to various types of endocytosed material and our CLEM analysis of double membrane SIF demonstrated that fluid phase markers accumulate only between the inner and outer membrane of these structures, a space continual with endosomal lumen. Our work reveals how manipulation of the endosomal membrane system by an intracellular pathogen results in a unique tubular membrane compartmentalization of the host cell, generating a shielded niche permissive for intracellular proliferation of Salmonella.",2014 Sep 25,"['Krieger, Viktoria', 'Liebl, David', 'Zhang, Yuying', 'Rajashekar, Roopa', 'Chlanda, Petr', 'Giesker, Katrin', 'Chikkaballi, Deepak', 'Hensel, Michael']",PLoS Pathog,,,True
d4b5a78a1ab61e4e94bf8478c47e6f5e2ef33086,PMC,High-Throughput Sequencing and De Novo Assembly of the Isatis indigotica Transcriptome,http://dx.doi.org/10.1371/journal.pone.0102963,PMC4178013,25259890,CC BY,"BACKGROUND: Isatis indigotica, the source of the traditional Chinese medicine Radix isatidis (Ban-Lan-Gen), is an extremely important economical crop in China. To facilitate biological, biochemical and molecular research on the medicinal chemicals in I. indigotica, here we report the first I. indigotica transcriptome generated by RNA sequencing (RNA-seq). RESULTS: RNA-seq library was created using RNA extracted from a mixed sample including leaf and root. A total of 33,238 unigenes were assembled from more than 28 million of high quality short reads. The quality of the assembly was experimentally examined by cDNA sequencing of seven randomly selected unigenes. Based on blast search 28,184 unigenes had a hit in at least one of the protein and nucleotide databases used in this study, and 8 unigenes were found to be associated with biosynthesis of indole and its derivatives. According to Gene Ontology classification, 22,365 unigenes were categorized into 48 functional groups. Furthermore, Clusters of Orthologous Group and Swiss-Port annotation were assigned for 7,707 and 18,679 unigenes, respectively. Analysis of repeat motifs identified 6,400 simple sequence repeat markers in 4,509 unigenes. CONCLUSION: Our data provide a comprehensive sequence resource for molecular study of I. indigotica. Our results will facilitate studies on the functions of genes involved in the indole alkaloid biosynthesis pathway and on metabolism of nitrogen and indole alkaloids in I. indigotica and its related species.",2014 Sep 26,"['Tang, Xiaoqing', 'Xiao, Yunhua', 'Lv, Tingting', 'Wang, Fangquan', 'Zhu, QianHao', 'Zheng, Tianqing', 'Yang, Jie']",PLoS One,,,True
27b5819a442f4af88897625612d73a398b439bfd,PMC,Modulation of Stop Codon Read-Through Efficiency and Its Effect on the Replication of Murine Leukemia Virus,http://dx.doi.org/10.1128/JVI.00898-14,PMC4178896,24991001,CC BY,"Translational readthrough—suppression of termination at a stop codon—is exploited in the replication cycles of several viruses and represents a potential target for antiviral intervention. In the gammaretroviruses, typified by Moloney murine leukemia virus (MuLV), gag and pol are in the same reading frame, separated by a UAG stop codon, and termination codon readthrough is required for expression of the viral Gag-Pol fusion protein. Here, we investigated the effect on MuLV replication of modulating readthrough efficiency. We began by manipulating the readthrough signal in the context of an infectious viral clone to generate a series of MuLV variants in which readthrough was stimulated or reduced. In carefully controlled infectivity assays, it was found that reducing the MuLV readthrough efficiency only 4-fold led to a marked defect and that a 10-fold reduction essentially abolished replication. However, up to an ∼8.5-fold stimulation of readthrough (up to 60% readthrough) was well tolerated by the virus. These high levels of readthrough were achieved using a two-plasmid system, with Gag and Gag-Pol expressed from separate infectious clones. We also modulated readthrough by silencing expression of eukaryotic release factors 1 and 3 (eRF1 and eRF3) or by introducing aminoglycosides into the cells. The data obtained indicate that gammaretroviruses tolerate a substantial excess of viral Gag-Pol synthesis but are very sensitive to a reduction in levels of this polyprotein. Thus, as is also the case for ribosomal frameshifting, antiviral therapies targeting readthrough with inhibitory agents are likely to be the most beneficial. IMPORTANCE Many pathogenic RNA viruses and retroviruses use ribosomal frameshifting or stop codon readthrough to regulate expression of their replicase enzymes. These translational “recoding” processes are potential targets for antiviral intervention, but we have only a limited understanding of the consequences to virus replication of modulating the efficiency of recoding, particularly for those viruses employing readthrough. In this paper, we describe the first systematic analysis of the effect of increasing or decreasing readthrough efficiency on virus replication using the gammaretrovirus MuLV as a model system. We find unexpectedly that MuLV replication is only slightly inhibited by substantial increases in readthrough frequency, but as with other viruses that use recoding strategies, replication is quite sensitive to even modest reductions. These studies provide insights into both the readthrough process and MuLV replication and have implications for the selection of antivirals against gammaretroviruses.",2014 Sep,"['Csibra, Eszter', 'Brierley, Ian', 'Irigoyen, Nerea']",J Virol,,,True
c9931d8718e491e3002bbf42aec7cde49e93bac5,PMC,The unfolded protein response in virus infections,http://dx.doi.org/10.3389/fmicb.2014.00518,PMC4179733,25324837,CC BY,,2014 Sep 30,"Chan, Shiu-Wan",Front Microbiol,,,True
4f25223579f443edc058800f30c4fe8847a6ab57,PMC,Application of WHO’s guideline for the selection of sentinel sites for hospital-based influenza surveillance in Indonesia,http://dx.doi.org/10.1186/1472-6963-14-424,PMC4179842,25248619,CC BY,"BACKGROUND: A sentinel hospital-based severe acute respiratory infection (SARI) surveillance system was established in Indonesia in 2013. Deciding on the number, geographic location and hospitals to be selected as sentinel sites was a challenge. Based on the recently published WHO guideline for influenza surveillance (2012), this study presents the process for hospital sentinel site selection. METHODS: From the 2,165 hospitals in Indonesia, the first step was to shortlist to hospitals that had previously participated in respiratory disease surveillance systems and had acceptable surveillance performance history. The second step involved categorizing the shortlist according to five regions in Indonesia to maximize geographic representativeness. A checklist was developed based on the WHO recommended attributes for sentinel site selection including stability, feasibility, representativeness and the availability of data to enable disease burden estimation. Eight hospitals, a maximum of two per geographic region, were visited for checklist administration. Checklist findings from the eight hospitals were analyzed and sentinel sites selected in the third step. RESULTS: Six hospitals could be selected based on resources available to ensure system stability over a three-year period. For feasibility, all eight hospitals visited had mechanisms for specimen shipment and the capacity to report surveillance data, but two had limited motivation for system participation. For representativeness, the eight hospitals were geographically dispersed around Indonesia, and all could capture cases in all age and socio-economic groups. All eight hospitals had prerequisite population data to enable disease burden estimation. The two hospitals with low motivation were excluded and the remaining six were selected as sentinel sites. CONCLUSIONS: The multi-step process enabled sentinel site selection based on the WHO recommended attributes that emphasize right-sizing the surveillance system to ensure its stability and maximizing its geographic representativeness. This experience may guide other countries interested in adopting WHO’s influenza surveillance standards for sentinel site selection.",2014 Sep 23,"['Susilarini, Ni Ketut', 'Sitorus, Martahan', 'Praptaningsih, Catharina Yekti', 'Sampurno, Ondri Dwi', 'Bratasena, Arie', 'Mulyadi, Ester', 'Rusli, Roselinda', 'Fandil, Ahmad', 'Mangiri, Amalya', 'Apsari, Hana', 'Hariyanto, Edy', 'Samaan, Gina']",BMC Health Serv Res,,,True
db97b6fadbd7b65de3e513beec8f3eca89bac377,PMC,An evaluation of a liquid antimicrobial (Sal CURB®) for reducing the risk of porcine epidemic diarrhea virus infection of naïve pigs during consumption of contaminated feed,http://dx.doi.org/10.1186/s12917-014-0220-9,PMC4179854,25253192,CC BY,"BACKGROUND: Since its initial detection in May 2013, porcine epidemic diarrhea virus (PEDV) has spread rapidly throughout the US swine industry. Recently, contaminated feed was confirmed as a vehicle for PEDV infection of naïve piglets. This research provides in vivo data supporting the ability of a liquid antimicrobial product to reduce this risk. RESULTS: Sal CURB® (Kemin Industries, Des Moines, IA, USA) is a FDA-approved liquid antimicrobial used to control Salmonella contamination in poultry and swine diets. To test its effect against PEDV, Sal CURB®-treated feed was spiked with a stock isolate of PEDV (Ct = 25.22), which PEDV-naïve piglets were allowed to ingest via natural feeding behavior (ad libitum) for a 14-day period. For the purpose of a positive control, a separate group of piglets was allowed to ingest non-treated (Sal CURB®-free) feed also spiked with stock PEDV (Ct = 25.22). A negative control group received PEDV-free feed. Clinical signs of PEDV infection (vomiting and diarrhea) and viral shedding in feces were observed in the positive control group 2–3 days post-consumption of non-treated feed. In contrast, no evidence of infection was observed in pigs fed Sal CURB®-treated feed or in the negative controls throughout the 14-day study period. In addition, the Sal CURB®-treated feed samples had higher (p < 0.0001) mean PEDV Ct values than samples from the positive control group. CONCLUSIONS: These data provide proof of concept that feed treated with Sal CURB® can serve as a means to reduce the risk of PEDV infection through contaminated feed. Furthermore, the results from the positive control group provide additional proof of concept regarding the ability of contaminated feed to serve as a risk factor for PEDV infection of naïve piglets.",2014 Sep 25,"['Dee, Scott', 'Neill, Casey', 'Clement, Travis', 'Christopher-Hennings, Jane', 'Nelson, Eric']",BMC Vet Res,,,True
db0f13123f5ba69c4a2b52b2d87fb2f5cd350c3c,PMC,Comparison of Antibodies Hydrolyzing Myelin Basic Protein from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis,http://dx.doi.org/10.1371/journal.pone.0107807,PMC4180057,25265393,CC BY,"It was found that antibodies (Abs) against myelin basic protein (MBP) are the major components of the antibody response in multiple sclerosis (MS) patients. We have recently shown that IgGs from sera of MS patients are active in the hydrolysis of MBP. However, in literature there are no available data concerning possible MBP-hydrolyzing Abs in cerebrospinal fluid (CSF) of MS patients. We have shown that the average content of IgGs in their sera is about 195-fold higher than that in their CSF. Here we have compared, for the first time, the average content of lambda- and kappa-IgGs as well as IgGs of four different subclasses (IgG1-IgG4) in CSF and sera of MS patients. The average relative content of lambda-IgGs and kappa –IgGs in the case of CSFs (8.0 and 92.0%) and sera (12.3 and 87.7%) are comparable, while IgG1, IgG2, IgG3, and IgG4: CSF - 40.4, 49.0, 8.2, and 2.5% of total IgGs, respectively and the sera - 53.6, 36.0, 5.6, and 4.8%, decreased in different order. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We present first evidence showing that IgGs from CSF efficiently hydrolyze MBP and that their average specific catalytic activity is unpredictably ∼54-fold higher than that of Abs from sera of the same MS patients. Some possible reasons of these findings are discussed. We suggest that anti-MBP abzymes of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development.",2014 Sep 29,"['Doronin, Visilii B.', 'Parkhomenko, Taisiya A.', 'Castellazzi, Massimiliano', 'Padroni, Marina', 'Pastore, Michela', 'Buneva, Valentina N.', 'Granieri, Enrico', 'Nevinsky, Georgy A.']",PLoS One,,,True
a286d1120f3b36b22f1b9e4e6409cad9b8471370,PMC,Recognizing flu-like symptoms from videos,http://dx.doi.org/10.1186/1471-2105-15-300,PMC4180141,25217118,CC BY,"BACKGROUND: Vision-based surveillance and monitoring is a potential alternative for early detection of respiratory disease outbreaks in urban areas complementing molecular diagnostics and hospital and doctor visit-based alert systems. Visible actions representing typical flu-like symptoms include sneeze and cough that are associated with changing patterns of hand to head distances, among others. The technical difficulties lie in the high complexity and large variation of those actions as well as numerous similar background actions such as scratching head, cell phone use, eating, drinking and so on. RESULTS: In this paper, we make a first attempt at the challenging problem of recognizing flu-like symptoms from videos. Since there was no related dataset available, we created a new public health dataset for action recognition that includes two major flu-like symptom related actions (sneeze and cough) and a number of background actions. We also developed a suitable novel algorithm by introducing two types of Action Matching Kernels, where both types aim to integrate two aspects of local features, namely the space-time layout and the Bag-of-Words representations. In particular, we show that the Pyramid Match Kernel and Spatial Pyramid Matching are both special cases of our proposed kernels. Besides experimenting on standard testbed, the proposed algorithm is evaluated also on the new sneeze and cough set. Empirically, we observe that our approach achieves competitive performance compared to the state-of-the-arts, while recognition on the new public health dataset is shown to be a non-trivial task even with simple single person unobstructed view. CONCLUSIONS: Our sneeze and cough video dataset and newly developed action recognition algorithm is the first of its kind and aims to kick-start the field of action recognition of flu-like symptoms from videos. It will be challenging but necessary in future developments to consider more complex real-life scenario of detecting these actions simultaneously from multiple persons in possibly crowded environments.",2014 Sep 12,"['Thi, Tuan Hue', 'Wang, Li', 'Ye, Ning', 'Zhang, Jian', 'Maurer-Stroh, Sebastian', 'Cheng, Li']",BMC Bioinformatics,,,True
36ac477a0485cd6f631502a5fe2e471db2210799,PMC,Procalcitonin guidance for reduction of antibiotic use in patients hospitalized with severe acute exacerbations of asthma: a randomized controlled study with 12-month follow-up,http://dx.doi.org/10.1186/s13054-014-0471-7,PMC4180966,25189222,CC BY,"INTRODUCTION: Patients with severe acute exacerbations of asthma often receive inappropriate antibiotic treatment. We aimed to determine whether serum procalcitonin (PCT) levels can effectively and safely reduce antibiotic exposure in patients experiencing exacerbations of asthma. METHODS: In this randomized controlled trial, a total of 216 patients requiring hospitalization for severe acute exacerbations of asthma were screened for eligibility to participate and 169 completed the 12-month follow-up visit. Patients were randomized to either PCT-guided (PCT group) or standard (control group) antimicrobial therapy. In the control group, patients received antibiotics according to the attending physician’s discretion; in the PCT group, patients received antibiotics according to an algorithm based on serum PCT levels. The primary end point was antibiotic exposure; secondary end points were clinical recovery, length of hospital stay, clinical and laboratory parameters, spirometry, number of asthma exacerbations, emergency room visits, hospitalizations and need for corticosteroid use due to asthma. RESULTS: PCT guidance reduced antibiotic prescription (48.9% versus 87.8%, respectively; P < 0.001) and antibiotic exposure (relative risk, 0.56; 95% confidence interval, 0.44 to 0.70; P < 0.001) compared to standard therapy. There were no significant differences in clinical recovery, length of hospital stay or clinical, laboratory and spirometry outcomes in both groups. Number of asthma exacerbations, emergency room visits, hospitalizations and need for corticosteroid use due to asthma were similar during the 12-month follow-up period. CONCLUSION: A PCT-guided strategy allows antibiotic exposure to be reduced in patients with severe acute exacerbation of asthma without apparent harm. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR-TRC-12002534 (registered 26 September 2012)",2014 Sep 5,"['Long, Wei', 'Li, Li-juan', 'Huang, Gao-zhong', 'Zhang, Xue-min', 'Zhang, Yi-cui', 'Tang, Jian-guo', 'Zhang, Yu', 'Lu, Gang']",Crit Care,,,True
2d315ee4d1e5819f972a999a7cc1a1c83a8993e5,PMC,Graph-distance distribution of the Boltzmann ensemble of RNA secondary structures,http://dx.doi.org/10.1186/1748-7188-9-19,PMC4181469,25285153,CC BY,"BACKGROUND: Large RNA molecules are often composed of multiple functional domains whose spatial arrangement strongly influences their function. Pre-mRNA splicing, for instance, relies on the spatial proximity of the splice junctions that can be separated by very long introns. Similar effects appear in the processing of RNA virus genomes. Albeit a crude measure, the distribution of spatial distances in thermodynamic equilibrium harbors useful information on the shape of the molecule that in turn can give insights into the interplay of its functional domains. RESULT: Spatial distance can be approximated by the graph-distance in RNA secondary structure. We show here that the equilibrium distribution of graph-distances between a fixed pair of nucleotides can be computed in polynomial time by means of dynamic programming. While a naïve implementation would yield recursions with a very high time complexity of O(n(6)D(5)) for sequence length n and D distinct distance values, it is possible to reduce this to O(n(4)) for practical applications in which predominantly small distances are of of interest. Further reductions, however, seem to be difficult. Therefore, we introduced sampling approaches that are much easier to implement. They are also theoretically favorable for several real-life applications, in particular since these primarily concern long-range interactions in very large RNA molecules. CONCLUSIONS: The graph-distance distribution can be computed using a dynamic programming approach. Although a crude approximation of reality, our initial results indicate that the graph-distance can be related to the smFRET data. The additional file and the software of our paper are available from http://www.rna.uni-jena.de/RNAgraphdist.html.",2014 Sep 11,"['Qin, Jing', 'Fricke, Markus', 'Marz, Manja', 'Stadler, Peter F', 'Backofen, Rolf']",Algorithms Mol Biol,,,True
be2fad939fdfc83bded3b06dee772e6479049f9e,PMC,Graph-distance distribution of the Boltzmann ensemble of RNA secondary structures,http://dx.doi.org/10.1186/1748-7188-9-19,PMC4181469,25285153,CC BY,"BACKGROUND: Large RNA molecules are often composed of multiple functional domains whose spatial arrangement strongly influences their function. Pre-mRNA splicing, for instance, relies on the spatial proximity of the splice junctions that can be separated by very long introns. Similar effects appear in the processing of RNA virus genomes. Albeit a crude measure, the distribution of spatial distances in thermodynamic equilibrium harbors useful information on the shape of the molecule that in turn can give insights into the interplay of its functional domains. RESULT: Spatial distance can be approximated by the graph-distance in RNA secondary structure. We show here that the equilibrium distribution of graph-distances between a fixed pair of nucleotides can be computed in polynomial time by means of dynamic programming. While a naïve implementation would yield recursions with a very high time complexity of O(n(6)D(5)) for sequence length n and D distinct distance values, it is possible to reduce this to O(n(4)) for practical applications in which predominantly small distances are of of interest. Further reductions, however, seem to be difficult. Therefore, we introduced sampling approaches that are much easier to implement. They are also theoretically favorable for several real-life applications, in particular since these primarily concern long-range interactions in very large RNA molecules. CONCLUSIONS: The graph-distance distribution can be computed using a dynamic programming approach. Although a crude approximation of reality, our initial results indicate that the graph-distance can be related to the smFRET data. The additional file and the software of our paper are available from http://www.rna.uni-jena.de/RNAgraphdist.html.",2014 Sep 11,"['Qin, Jing', 'Fricke, Markus', 'Marz, Manja', 'Stadler, Peter F', 'Backofen, Rolf']",Algorithms Mol Biol,,,True
8bcded9bf20651adee9df9dc56030291f0b881fb,PMC,Epidemiology of respiratory viral infections in children enrolled in a study of influenza vaccine effectiveness,http://dx.doi.org/10.1111/irv.12229,PMC4181477,24483149,CC BY,"BACKGROUND: Influenza-like illness (ILI) confers a high annual morbidity in young children. We report the epidemiology of ILIs in children who participated in an influenza vaccine effectiveness study during the 2010 Southern Hemisphere influenza season in Sydney, Australia. METHODS: Children aged 0·5–3 years were prospectively recruited from child care centres (CCCs). We classified them as fully vaccinated, partially vaccinated and unvaccinated according to their receipt of unadjuvanted vaccines containing influenza A (H1N1)pdm09. For 13 weeks commencing 30 July 2010, parents reported when their children developed an ILI (fever ≥37·8°C/feverishness plus ≥1 respiratory symptom) and collected nose and/or throat swabs for multiplex respiratory virus polymerase chain reaction (PCR) testing. Health impacts were assessed by telephone interview at enrolment and two weeks after each ILI. RESULTS: There were 124 ILIs reported in 105 of 381 enrolled children. Swabs were taken in 117 ILIs: 175 viruses were identified from 103 swabs. Adeno- and rhinoviruses were most frequently identified; 44% of swabs yielded multiple viruses. No virus was associated with more severe symptoms, although rhinovirus-related ILIs lasted longer. Nose swabs had a higher virus detection rate than throat swabs. Influenza-vaccinated children were 1·6 times (P = 0·001) more likely than unvaccinated children to have a non-influenza ILI. CONCLUSION: Adeno- and rhinoviruses were the most common viruses causing ILI. Swabs taken by parents are an effective method for sample collection. Influenza-like illness was more common in children vaccinated against influenza in this observational study, but prior health-seeking behaviour may have contributed to this difference.",2014 May 31,"['Dierig, Alexa', 'Heron, Leon G', 'Lambert, Stephen B', 'Yin, Jiehui Kevin', 'Leask, Julie', 'Chow, Maria Yui Kwan', 'Sloots, Theo P', 'Nissen, Michael D', 'Ridda, Iman', 'Booy, Robert']",Influenza Other Respir Viruses,,,True
66fb607e8ee0e7b13f1abaedf0ed42451c8924a2,PMC,"Epidemiology of human adenovirus and molecular characterization of human adenovirus 55 in China, 2009–2012",http://dx.doi.org/10.1111/irv.12232,PMC4181478,24467816,CC BY,"BACKGROUND: Human adenovirus 55 (HAdV-55) has caused recent outbreaks of acute respiratory disease (ARD) among adults and military trainees. The active surveillance for HAdV infections was sparse in China, and current knowledge on the HAdV-type distributions and its molecular evolution is lacking. OBJECTIVES: To acquire better understanding on the prevalence and molecular evolution of HAdV-55 strains in China, for an informed strategy for disease control and prevention. POPULATION/METHODS: Nasopharyngeal aspirates were collected from hospitalized children with ARTI in Chongqing during 2009–2012. The genotype of HAdV isolates were determined by sequencing the partial hexon and fiber genes. Whole genome sequences of HAdV-55 were obtained for molecular evolution analysis. RESULTS: About 191 (8·55%) HAdV were detected in 2234 children, including 92 (48·2%) with HAdV-7, 72 (37·7%) with HAdV-3, 6 (3·1%) with HAdV-55, 5 (2·6%) with HAdV-5, 4 (2·1%) with HAdV-1, 1 (0·5%) with HAdV-2, and 11(5·8%) with untyped HAdV. Four of these children developed pneumonia, two of whom were diagnosed with severe pneumonia and/or encephalopathy. HAdV-55 isolates clustered with HAdV-11 sequences based on the hexon gene and clustered with HAdV-14 sequences based on the fiber gene and the whole genome. The overall evolutionary rates of hexon gene, fiber gene, and whole genome of HAdV-55 were estimated at 6·2 × 10(−5) s/s/y, 8·0 × 10(−5) s/s/y, and 1·7 × 10(−5) s/s/y, respectively. CONCLUSIONS: This study suggested HAdV-55 as an emerging infectious disease pathogen has conserved genetic structure and is closely related to each other. Further molecular investigation based on HAdV-55 of wider origin might facilitate understanding its diversity, dissemination, and transmission in China.",2014 May 28,"['Lu, Qing-Bin', 'Tong, Yi-Gang', 'Wo, Ying', 'Wang, Hong-Yu', 'Liu, En-Mei', 'Gray, Gregory C', 'Liu, Wei', 'Cao, Wu-Chun']",Influenza Other Respir Viruses,,,True
d1861375d64fea0dd4e02843a049792058ce6140,PMC,A systematic review of studies on forecasting the dynamics of influenza outbreaks,http://dx.doi.org/10.1111/irv.12226,PMC4181479,24373466,CC BY,"Forecasting the dynamics of influenza outbreaks could be useful for decision-making regarding the allocation of public health resources. Reliable forecasts could also aid in the selection and implementation of interventions to reduce morbidity and mortality due to influenza illness. This paper reviews methods for influenza forecasting proposed during previous influenza outbreaks and those evaluated in hindsight. We discuss the various approaches, in addition to the variability in measures of accuracy and precision of predicted measures. PubMed and Google Scholar searches for articles on influenza forecasting retrieved sixteen studies that matched the study criteria. We focused on studies that aimed at forecasting influenza outbreaks at the local, regional, national, or global level. The selected studies spanned a wide range of regions including USA, Sweden, Hong Kong, Japan, Singapore, United Kingdom, Canada, France, and Cuba. The methods were also applied to forecast a single measure or multiple measures. Typical measures predicted included peak timing, peak height, daily/weekly case counts, and outbreak magnitude. Due to differences in measures used to assess accuracy, a single estimate of predictive error for each of the measures was difficult to obtain. However, collectively, the results suggest that these diverse approaches to influenza forecasting are capable of capturing specific outbreak measures with some degree of accuracy given reliable data and correct disease assumptions. Nonetheless, several of these approaches need to be evaluated and their performance quantified in real-time predictions.",2014 May 23,"['Nsoesie, Elaine O', 'Brownstein, John S', 'Ramakrishnan, Naren', 'Marathe, Madhav V']",Influenza Other Respir Viruses,,,True
9543d56a69a743e9472e1955f27bfa935ae43942,PMC,Impact of 2009 pandemic influenza among Vietnamese children based on a population-based prospective surveillance from 2007 to 2011,http://dx.doi.org/10.1111/irv.12244,PMC4181797,24602158,CC BY,"BACKGROUND: Influenza virus is one of the major viral pathogens causing pediatric acute respiratory infection (ARI). The spread of pandemic influenza A (A(H1N1)pdm09) in 2009 around the globe had a huge impact on global health. OBJECTIVE: To investigate the impact of A(H1N1)pdm09 on pediatric ARI in Vietnam. STUDY DESIGN: An ongoing population-based prospective surveillance in central Vietnam was used. All children aged <15 years residing in Nha Trang city, enrolled to the ARI surveillance in Khanh Hoa General Hospital, from February 2007 through March 2011 were studied. Clinical data and nasopharyngeal swab samples were collected. Influenza A was detected and genotyped by multiplex polymerase chain reaction assays and sequencing. RESULTS: Among enrolled 2736 hospitalized ARI cases, 354 (13%) were positive for influenza A. Genotyping results revealed that seasonal H3N2 and H1N1 (sea-H1N1) viruses were cocirculating before A(H1N1)pdm09 appeared in July 2009. The A(H1N1)pdm09 replaced the sea-H1N1 after the pandemic. The majority of influenza A cases (90%) were aged <5 years with incidence rate of 537 (387–775) per 100 000 population. Annual incidence rates of hospitalized influenza cases for pre-, initial and post-pandemic periods among children aged <5 year were 474, 452, and 387 per 100 000, respectively. Children with A(H1N1)pdm09 were elder, visited the hospital earlier, less frequently had severe signs, and were less frequently associated with viral coinfection compared with seasonal influenza cases. CONCLUSIONS: The A(H1N1)pdm09 did not increase the influenza annual hospitalization incidence or disease severity compared with seasonal influenza among pediatric ARI cases in central Vietnam.",2014 Jul 7,"['Le, Minh Nhat', 'Yoshida, Lay Myint', 'Suzuki, Motoi', 'Nguyen, Hien Anh', 'Le, Huu Tho', 'Moriuchi, Hiroyuki', 'Dang, Duc Anh', 'Ariyoshi, Koya']",Influenza Other Respir Viruses,,,True
ef5fe7296ec8baf90d974cf5737af0da3ed403ea,PMC,"A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China",http://dx.doi.org/10.1111/irv.12257,PMC4181804,24828783,CC BY,"BACKGROUND: The epidemiology of local viral etiologies is essential for the management of viral respiratory tract infections. Limited data are available in China to describe the epidemiology of viral respiratory infections, especially in small–medium cities and rural areas. OBJECTIVES: To determine the viral etiology and seasonality of acute respiratory infections in hospitalized children, a 3-year study was conducted in Shenzhen, China. METHODS: Nasopharyngeal aspirates from eligible children were collected. Influenza and other respiratory viruses were tested by molecular assays simultaneously. Data were analyzed to describe the frequency and seasonality. RESULTS: Of the 2025 children enrolled in the study, 971 (48·0%) were positive for at least one viral pathogen, in which 890 (91·7%) were <4 years of age. The three most prevalent viruses were influenza A (IAV; 35·8%), respiratory syncytial virus (RSV; 30·5%) and human rhinovirus (HRV; 21·5%). Co-infections were found in 302 cases (31·1%), and dual viral infection was dominant. RSV, HRV and IAV were the most frequent viral agents involved in co-infection. On the whole, the obvious seasonal peaks mainly from March to May were observed with peak strength varying from 1 year to another. CONCLUSIONS: This study provides a basic profile of the epidemiology of acute respiratory viral infection in hospitalized children in Shenzhen. The spectrum of viruses in the study site is similar to that in other places, but the seasonality is closely related to geographic position, different from that in big cities in northern China and neighboring Hong Kong.",2014 Jul 14,"['He, Ying', 'Lin, Guang-Yu', 'Wang, Qiong', 'Cai, Xiao-Ying', 'Zhang, Yin-Hui', 'Lin, Chuang-Xing', 'Lu, Chang-Dong', 'Lu, Xue-Dong']",Influenza Other Respir Viruses,,,True
59914aa651a598b95b58825690eeb4477c7777ef,PMC,Impact of preceding respiratory viral infections on the clinical severity of patients with pneumococcal pneumonia,http://dx.doi.org/10.1111/irv.12265,PMC4181819,24962523,CC BY,"BACKGROUND: This study aimed to investigate the impact of preceding respiratory viral infections (RVI) on the clinical severity of pneumococcal pneumonia patients. METHODS: A retrospective observational study was conducted at a university hospital from January 2009 to March 2013. Study subjects included adults (aged ≥18 years) with pneumococcal pneumonia who had undergone laboratory tests for RVI. Multivariate logistic regression analysis was performed to identify risk factors associated with severe pneumococcal pneumonia, defined as severity with the Pneumonia Severity Index (PSI) score ≥91. RESULTS: In total, 191 patients with pneumococcal pneumonia were included for analysis and stratified into 2 groups: the severe group with a PSI score ≥91 (n = 99) and the non-severe group with a PSI score <91 (n = 92). Preceding RVIs were detected in 48 patients, including influenza A virus (n = 20), influenza B virus (n = 4), parainfluenza viruses (n = 5), metapneumovirus (n = 4), rhinovirus (n = 4), respiratory syncytial viruses (n = 6), coronaviruses (n = 2), and mixed viral infections (n = 3). In the multivariate logistic regression analysis, preceding RVIs (odds ratio [OR], 2·49; 95% confidence interval [CI], 1·10–5·60), male sex (OR, 2·58; 95% CI, 1·24–5·38), old age (OR, 2·92; 95% CI, 1·37–6·24), hypoalbuminemia (OR, 3·26; 95% CI, 1·56–6·84)], and azotemia (OR, 2·24; 95% CI, 1·08–4·67) were significantly associated with severe pneumococcal pneumonia. CONCLUSION: This study suggests that preceding RVIs might be one of the risk factors affecting the clinical severity of pneumococcal pneumonia.",2014 Sep 24,"['Yoon, Young Kyung', 'Yang, Kyung Sook', 'Sohn, Jang Wook', 'Lee, Chang Kyu', 'Kim, Min Ja']",Influenza Other Respir Viruses,,,True
3ddbaa41fdf3c15e1677fd5cbc0a7d6c7f1e51fc,PMC,Heat inactivation of the Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1111/irv.12261,PMC4181824,25074677,CC BY,"The culture supernatants of the emerging Middle East respiratory syndrome coronavirus (MERS-CoV) were submitted to three temperatures over time and tested for infectivity by TCID(50) method on Vero E6 cells. At 56°C, almost 25 minutes were necessary to reduce the initial titre by 4 log(10). Increasing temperature to 65°C had a strong negative effect on viral infectivity as virucidy dropped significantly to 1 minute. On the contrary, no significant decrease in titre was observed after 2 hours at 25°C. These data might be useful in establishing biosafety measures in laboratories against MERS-CoV.",2014 Sep 24,"['Leclercq, India', 'Batéjat, Christophe', 'Burguière, Ana M', 'Manuguerra, Jean-Claude']",Influenza Other Respir Viruses,,,True
47aa21ec26143c3b7a9ff3fa57eb20634cc41940,PMC,The Impact of “Omic” and Imaging Technologies on Assessing the Host Immune Response to Biodefence Agents,http://dx.doi.org/10.1155/2014/237043,PMC4182007,25333059,CC BY,"Understanding the interactions between host and pathogen is important for the development and assessment of medical countermeasures to infectious agents, including potential biodefence pathogens such as Bacillus anthracis, Ebola virus, and Francisella tularensis. This review focuses on technological advances which allow this interaction to be studied in much greater detail. Namely, the use of “omic” technologies (next generation sequencing, DNA, and protein microarrays) for dissecting the underlying host response to infection at the molecular level; optical imaging techniques (flow cytometry and fluorescence microscopy) for assessing cellular responses to infection; and biophotonic imaging for visualising the infectious disease process. All of these technologies hold great promise for important breakthroughs in the rational development of vaccines and therapeutics for biodefence agents.",2014 Sep 16,"['Tree, Julia A.', 'Flick-Smith, Helen', 'Elmore, Michael J.', 'Rowland, Caroline A.']",J Immunol Res,,,True
5721c27ac5defb5f651b26e7f45324c848212c06,PMC,Chimeric NP Non Coding Regions between Type A and C Influenza Viruses Reveal Their Role in Translation Regulation,http://dx.doi.org/10.1371/journal.pone.0109046,PMC4182659,25268971,CC BY,"Exchange of the non coding regions of the NP segment between type A and C influenza viruses was used to demonstrate the importance not only of the proximal panhandle, but also of the initial distal panhandle strength in type specificity. Both elements were found to be compulsory to rescue infectious virus by reverse genetics systems. Interestingly, in type A influenza virus infectious context, the length of the NP segment 5′ NC region once transcribed into mRNA was found to impact its translation, and the level of produced NP protein consequently affected the level of viral genome replication.",2014 Sep 30,"['Crescenzo-Chaigne, Bernadette', 'Barbezange, Cyril', 'Frigard, Vianney', 'Poulain, Damien', 'van der Werf, Sylvie']",PLoS One,,,True
865949791a49615aa67ae0444e5987348c82ba65,PMC,Identification of Host-Immune Response Protein Candidates in the Sera of Human Oral Squamous Cell Carcinoma Patients,http://dx.doi.org/10.1371/journal.pone.0109012,PMC4182798,25272005,CC BY,"One of the most common cancers worldwide is oral squamous cell carcinoma (OSCC), which is associated with a significant death rate and has been linked to several risk factors. Notably, failure to detect these neoplasms at an early stage represents a fundamental barrier to improving the survival and quality of life of OSCC patients. In the present study, serum samples from OSCC patients (n = 25) and healthy controls (n = 25) were subjected to two-dimensional gel electrophoresis (2-DE) and silver staining in order to identify biomarkers that might allow early diagnosis. In this regard, 2-DE spots corresponding to various up- and down-regulated proteins were sequenced via high-resolution MALDI-TOF mass spectrometry and analyzed using the MASCOT database. We identified the following differentially expressed host-specific proteins within sera from OSCC patients: leucine-rich α2-glycoprotein (LRG), alpha-1-B-glycoprotein (ABG), clusterin (CLU), PRO2044, haptoglobin (HAP), complement C3c (C3), proapolipoprotein A1 (proapo-A1), and retinol-binding protein 4 precursor (RBP4). Moreover, five non-host factors were detected, including bacterial antigens from Acinetobacter lwoffii, Burkholderia multivorans, Myxococcus xanthus, Laribacter hongkongensis, and Streptococcus salivarius. Subsequently, we analyzed the immunogenicity of these proteins using pooled sera from OSCC patients. In this regard, five of these candidate biomarkers were found to be immunoreactive: CLU, HAP, C3, proapo-A1 and RBP4. Taken together, our immunoproteomics approach has identified various serum biomarkers that could facilitate the development of early diagnostic tools for OSCC.",2014 Oct 1,"['Chen, Yeng', 'Azman, Siti Nuraishah', 'Kerishnan, Jesinda P.', 'Zain, Rosnah Binti', 'Chen, Yu Nieng', 'Wong, Yin-Ling', 'Gopinath, Subash C. B.']",PLoS One,,,True
8ba20a12c92103d82364b8abca49cfcd91d91c13,PMC,N-glycan Cryptic Antigens as Active Immunological Targets in Prostate Cancer Patients,http://dx.doi.org/10.4172/jpb.1000218,PMC4183219,25284963,CC BY,"Although tumor-associated abnormal glycosylation has been recognized for decades, information regarding host recognition of the evolving tumor glycome remains elusive. We report here a carbohydrate microarray analysis of a number of tumor-associated carbohydrates for their serum antibody reactivities and potential immunogenicity in humans. These are the precursors, cores and internal sequences of N-glycans. They are usually masked by other sugar moieties and belong to a class of glyco-antigens that are normally “cryptic”. However, viral expression of these carbohydrates may trigger host immune responses. For examples, HIV-1 and SARS-CoV display Man9 clusters and tri- or multi-antennary type II (Galβ1→4GlcNAc) chains (Tri/m-II), respectively; viral neutralizing antibodies often target these sugar moieties. We asked, therefore, whether prostate tumor expression of corresponding carbohydrates triggers antibody responses in vivo. Using carbohydrate microarrays, we analyzed a panel of human sera, including 17 samples from prostate cancer patients and 12 from men with Benign Prostatic Hyperplasia (BPH). We observed that IgG antibodies targeting the Man9- or Tri-/m-II-autoantigens are readily detectable in the sera of men with BPH, as well as those with cancer. Importantly, these antibody activities were selectively increased in prostate cancer patients. Thus, human immune systems actively recognize these N-glycan cryptic carbohydrates and produce targeting antibodies. This finding shads a light on a class of previously less studied immunological targets of human cancers. Identifying the diagnostic, prognostic and therapeutic values of these targets will require further investigation.",2012 Apr 30,"Wang, Denong",J Proteomics Bioinform,,,True
3abc03ade244048ff2dbe668caa5cb9cb61a19eb,PMC,N-glycan Cryptic Antigens as Active Immunological Targets in Prostate Cancer Patients,http://dx.doi.org/10.4172/jpb.1000218,PMC4183219,25284963,CC BY,"Although tumor-associated abnormal glycosylation has been recognized for decades, information regarding host recognition of the evolving tumor glycome remains elusive. We report here a carbohydrate microarray analysis of a number of tumor-associated carbohydrates for their serum antibody reactivities and potential immunogenicity in humans. These are the precursors, cores and internal sequences of N-glycans. They are usually masked by other sugar moieties and belong to a class of glyco-antigens that are normally “cryptic”. However, viral expression of these carbohydrates may trigger host immune responses. For examples, HIV-1 and SARS-CoV display Man9 clusters and tri- or multi-antennary type II (Galβ1→4GlcNAc) chains (Tri/m-II), respectively; viral neutralizing antibodies often target these sugar moieties. We asked, therefore, whether prostate tumor expression of corresponding carbohydrates triggers antibody responses in vivo. Using carbohydrate microarrays, we analyzed a panel of human sera, including 17 samples from prostate cancer patients and 12 from men with Benign Prostatic Hyperplasia (BPH). We observed that IgG antibodies targeting the Man9- or Tri-/m-II-autoantigens are readily detectable in the sera of men with BPH, as well as those with cancer. Importantly, these antibody activities were selectively increased in prostate cancer patients. Thus, human immune systems actively recognize these N-glycan cryptic carbohydrates and produce targeting antibodies. This finding shads a light on a class of previously less studied immunological targets of human cancers. Identifying the diagnostic, prognostic and therapeutic values of these targets will require further investigation.",2012 Apr 30,"Wang, Denong",J Proteomics Bioinform,,,False
05445d95af0648219e8eb051ab3015b2a4615027,PMC,Immune Biomarkers Predictive of Respiratory Viral Infection in Elderly Nursing Home Residents,http://dx.doi.org/10.1371/journal.pone.0108481,PMC4183538,25275464,CC BY,"OBJECTIVE: To determine if immune phenotypes associated with immunosenescence predict risk of respiratory viral infection in elderly nursing home residents. METHODS: Residents ≥65 years from 32 nursing homes in 4 Canadian cities were enrolled in Fall 2009, 2010 and 2011, and followed for one influenza season. Following influenza vaccination, peripheral blood mononuclear cells (PBMCs) were obtained and analysed by flow cytometry for T-regs, CD4+ and CD8+ T-cell subsets (CCR7+CD45RA+, CCR7-CD45RA+ and CD28-CD57+) and CMV-reactive CD4+ and CD8+ T-cells. Nasopharyngeal swabs were obtained and tested for viruses in symptomatic residents. A Cox proportional hazards model adjusted for age, sex and frailty, determined the relationship between immune phenotypes and time to viral infection. RESULTS: 1072 residents were enrolled; median age 86 years and 72% female. 269 swabs were obtained, 87 were positive for virus: influenza (24%), RSV (14%), coronavirus (32%), rhinovirus (17%), human metapneumovirus (9%) and parainfluenza (5%). In multivariable analysis, high T-reg% (HR 0.41, 95% CI 0.20–0.81) and high CMV-reactive CD4+ T-cell% (HR 1.69, 95% CI 1.03–2.78) were predictive of respiratory viral infection. CONCLUSIONS: In elderly nursing home residents, high CMV-reactive CD4+ T-cells were associated with an increased risk and high T-regs were associated with a reduced risk of respiratory viral infection.",2014 Oct 2,"['Johnstone, Jennie', 'Parsons, Robin', 'Botelho, Fernando', 'Millar, Jamie', 'McNeil, Shelly', 'Fulop, Tamas', 'McElhaney, Janet', 'Andrew, Melissa K.', 'Walter, Stephen D.', 'Devereaux, P. J.', 'Malekesmaeili, Mehrnoush', 'Brinkman, Ryan R.', 'Mahony, James', 'Bramson, Jonathan', 'Loeb, Mark']",PLoS One,,,True
97229e8af52b75aa9ac0f0eb530bf89f7f5ec134,PMC,Cyclophilin A Associates with Enterovirus-71 Virus Capsid and Plays an Essential Role in Viral Infection as an Uncoating Regulator,http://dx.doi.org/10.1371/journal.ppat.1004422,PMC4183573,25275585,CC BY,"Viruses utilize host factors for their efficient proliferation. By evaluating the inhibitory effects of compounds in our library, we identified inhibitors of cyclophilin A (CypA), a known immunosuppressor with peptidyl-prolyl cis-trans isomerase activity, can significantly attenuate EV71 proliferation. We demonstrated that CypA played an essential role in EV71 entry and that the RNA interference-mediated reduction of endogenous CypA expression led to decreased EV71 multiplication. We further revealed that CypA directly interacted with and modified the conformation of H-I loop of the VP1 protein in EV71 capsid, and thus regulated the uncoating process of EV71 entry step in a pH-dependent manner. Our results aid in the understanding of how host factors influence EV71 life cycle and provide new potential targets for developing antiviral agents against EV71 infection.",2014 Oct 2,"['Qing, Jie', 'Wang, Yaxin', 'Sun, Yuna', 'Huang, Jiaoyan', 'Yan, Wenzhong', 'Wang, Jinglan', 'Su, Dan', 'Ni, Cheng', 'Li, Jian', 'Rao, Zihe', 'Liu, Lei', 'Lou, Zhiyong']",PLoS Pathog,,,True
1542e8e707bd5fa1cb6b3919722fc30ced018c1f,PMC,Lack of a 5.9 kDa Peptide C-Terminal Fragment of Fibrinogen α Chain Precedes Fibrosis Progression in Patients with Liver Disease,http://dx.doi.org/10.1371/journal.pone.0109254,PMC4183580,25275549,CC BY,"Early detection of fibrosis progression is of major relevance for the diagnosis and management of patients with liver disease. This study was designed to find non-invasive biomarkers for fibrosis in a clinical context where this process occurs rapidly, HCV-positive patients who underwent liver transplantation (LT). We analyzed 93 LT patients with HCV recurrence, 41 non-LT patients with liver disease showing a fibrosis stage F≥1 and 9 patients without HCV recurrence who received antiviral treatment before LT, as control group. Blood obtained from 16 healthy subjects was also analyzed. Serum samples were fractionated by ion exchange chromatography and their proteomic profile was analyzed by SELDI-TOF-MS. Characterization of the peptide of interest was performed by ion chromatography and electrophoresis, followed by tandem mass spectrometry identification. Marked differences were observed between the serum proteome profile of LT patients with early fibrosis recurrence and non-recurrent LT patients. A robust peak intensity located at 5905 m/z was the distinguishing feature of non-recurrent LT patients. However, the same peak was barely detected in recurrent LT patients. Similar results were found when comparing samples of healthy subjects with those of non-LT fibrotic patients, indicating that our findings were not related to either LT or HCV infection. Using tandem mass-spectrometry, we identified the protein peak as a C-terminal fragment of the fibrinogen α chain. Cell culture experiments demonstrated that TGF-β reduces α-fibrinogen mRNA expression and 5905 m/z peak intensity in HepG2 cells, suggesting that TGF-β activity regulates the circulating levels of this protein fragment. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen α chain as an early serum biomarker of fibrogenic processes in patients with liver disease.",2014 Oct 2,"['Marfà, Santiago', 'Crespo, Gonzalo', 'Reichenbach, Vedrana', 'Forns, Xavier', 'Casals, Gregori', 'Morales-Ruiz, Manuel', 'Navasa, Miquel', 'Jiménez, Wladimiro']",PLoS One,,,True
b84e5b51b40b345b68445d68483cc478e9ce5beb,PMC,Characterization of Uncultivable Bat Influenza Virus Using a Replicative Synthetic Virus,http://dx.doi.org/10.1371/journal.ppat.1004420,PMC4183581,25275541,CC BY,"Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV). Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1). This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2) showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses.",2014 Oct 2,"['Zhou, Bin', 'Ma, Jingjiao', 'Liu, Qinfang', 'Bawa, Bhupinder', 'Wang, Wei', 'Shabman, Reed S.', 'Duff, Michael', 'Lee, Jinhwa', 'Lang, Yuekun', 'Cao, Nan', 'Nagy, Abdou', 'Lin, Xudong', 'Stockwell, Timothy B.', 'Richt, Juergen A.', 'Wentworth, David E.', 'Ma, Wenjun']",PLoS Pathog,,,True
eb8769154d6a5a4a44f5cea8a1b92082f9c278a6,PMC,Nerve growth factor reduces amiloride‐sensitive Na(+) transport in human airway epithelial cells,http://dx.doi.org/10.14814/phy2.12073,PMC4187554,25347857,CC BY,"Nerve growth factor (NGF) is overexpressed in patients with inflammatory lung diseases, including virus infections. Airway surface liquid (ASL), which is regulated by epithelial cell ion transport, is essential for normal lung function. No information is available regarding the effect of NGF on ion transport of airway epithelium. To investigate whether NGF can affect ion transport, human primary air‐interface cultured epithelial cells were placed in Ussing chambers to obtain transepithelial voltage (−7.1 ± 3.4 mV), short‐circuit current (I(sc), 5.9 ± 1.0 μA), and transepithelial resistance (750 Ω·cm(2)), and to measure responses to ion transport inhibitors. Amiloride (apical, 3.5 × 10(−5) mol/L) decreased I(sc) by 55.3%. Apically applied NGF (1 ng/mL) reduced I(sc) by 5.3% in 5 min; basolaterally applied NGF had no effect. The response to amiloride was reduced (41.6%) in the presence of NGF. K‐252a (10 nmol/L, apical) did not itself affect Na(+) transport, but it attenuated the NGF‐induced reduction in Na(+) transport, indicating the participation of the trkA receptor in the NGF‐induced reduction in Na(+) transport. PD‐98059 (30 μmol/L, apical and basolateral) did not itself affect Na(+) transport, but attenuated the NGF‐induced reduction in Na(+) transport, indicating that trkA activated the Erk 1/2 signaling cascade. NGF stimulated phosphorylation of Erk 1/2 and the β‐subunit of ENaC. K‐252a and PD‐98059 inhibited these responses. NGF had no effect on I(sc) in the presence of apical nystatin (50 μmol/L). These results indicate that NGF inhibits Na(+) transport through a trkA‐Erk 1/2‐activated signaling pathway linked to ENaC phosphorylation.",2014 Jul 17,"['Shimko, Michael J.', 'Zaccone, Eric J.', 'Thompson, Janet A.', 'Schwegler‐Berry, Diane', 'Kashon, Michael L.', 'Fedan, Jeffrey S.']",Physiol Rep,,,True
d7817865765ddf7b0e1635e74b7a9393d0979a66,PMC,Visualization of a substrate-induced productive conformation of the catalytic triad of the Neisseria meningitidis peptidoglycan O-acetylesterase reveals mechanistic conservation in SGNH esterase family members,http://dx.doi.org/10.1107/S1399004714016770,PMC4188005,25286847,CC BY,"Peptidoglycan O-acetylesterase (Ape1), which is required for host survival in Neisseria sp., belongs to the diverse SGNH hydrolase superfamily, which includes important viral and bacterial virulence factors. Here, multi-domain crystal structures of Ape1 with an SGNH catalytic domain and a newly identified putative peptidoglycan-detection module are reported. Enzyme catalysis was performed in Ape1 crystals and key catalytic intermediates along the SGNH esterase hydrolysis reaction pathway were visualized, revealing a substrate-induced productive conformation of the catalytic triad, a mechanistic detail that has not previously been observed. This substrate-induced productive conformation of the catalytic triad shifts the established dogma on these enzymes, generating valuable insight into the structure-based design of drugs targeting the SGNH esterase superfamily.",2014 Sep 27,"['Williams, Allison H.', 'Veyrier, Frédéric J.', 'Bonis, Mathilde', 'Michaud, Yann', 'Raynal, Bertrand', 'Taha, Muhamed-Kheir', 'White, Stephen W.', 'Haouz, Ahmed', 'Boneca, Ivo G.']",Acta Crystallogr D Biol Crystallogr,,,True
56f4b284986e2ede2a15c810ad7b342cbfcc1fd6,PMC,Visualization of a substrate-induced productive conformation of the catalytic triad of the Neisseria meningitidis peptidoglycan O-acetylesterase reveals mechanistic conservation in SGNH esterase family members,http://dx.doi.org/10.1107/S1399004714016770,PMC4188005,25286847,CC BY,"Peptidoglycan O-acetylesterase (Ape1), which is required for host survival in Neisseria sp., belongs to the diverse SGNH hydrolase superfamily, which includes important viral and bacterial virulence factors. Here, multi-domain crystal structures of Ape1 with an SGNH catalytic domain and a newly identified putative peptidoglycan-detection module are reported. Enzyme catalysis was performed in Ape1 crystals and key catalytic intermediates along the SGNH esterase hydrolysis reaction pathway were visualized, revealing a substrate-induced productive conformation of the catalytic triad, a mechanistic detail that has not previously been observed. This substrate-induced productive conformation of the catalytic triad shifts the established dogma on these enzymes, generating valuable insight into the structure-based design of drugs targeting the SGNH esterase superfamily.",2014 Sep 27,"['Williams, Allison H.', 'Veyrier, Frédéric J.', 'Bonis, Mathilde', 'Michaud, Yann', 'Raynal, Bertrand', 'Taha, Muhamed-Kheir', 'White, Stephen W.', 'Haouz, Ahmed', 'Boneca, Ivo G.']",Acta Crystallogr D Biol Crystallogr,,,False
1469710f9b5dce0601307791210b86a225dd1be1,PMC,Unusual Influenza A Viruses in Bats,http://dx.doi.org/10.3390/v6093438,PMC4189031,25256392,CC BY,"Influenza A viruses infect a remarkably diverse number of hosts. Two completely new influenza A virus subtypes were recently discovered in bats, dramatically expanding the host range of the virus. These bat viruses are extremely divergent from all other known strains and likely have unique replication cycles. Phylogenetic analysis indicates long-term, isolated evolution in bats. This is supported by a high seroprevalence in sampled bat populations. As bats represent ~20% of all classified mammals, these findings suggests the presence of a massive cryptic reservoir of poorly characterized influenza A viruses. Here, we review the exciting progress made on understanding these newly discovered viruses, and discuss their zoonotic potential.",2014 Sep 17,"Mehle, Andrew",Viruses,,,True
2fd379bd7d8ce15f444b2fa608e6c5899441d52a,PMC,IFITM Proteins Inhibit Entry Driven by the MERS-Coronavirus Spike Protein: Evidence for Cholesterol-Independent Mechanisms,http://dx.doi.org/10.3390/v6093683,PMC4189045,25256397,CC BY,"The interferon-inducible transmembrane (IFITM) proteins 1, 2 and 3 inhibit the host cell entry of several enveloped viruses, potentially by promoting the accumulation of cholesterol in endosomal compartments. IFITM3 is essential for control of influenza virus infection in mice and humans. In contrast, the role of IFITM proteins in coronavirus infection is less well defined. Employing a retroviral vector system for analysis of coronavirus entry, we investigated the susceptibility of human-adapted and emerging coronaviruses to inhibition by IFITM proteins. We found that entry of the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is sensitive to inhibition by IFITM proteins. In 293T cells, IFITM-mediated inhibition of cellular entry of the emerging MERS- and SARS-CoV was less efficient than blockade of entry of the globally circulating human coronaviruses 229E and NL63. Similar differences were not observed in A549 cells, suggesting that cellular context and/or IFITM expression levels can impact inhibition efficiency. The differential IFITM-sensitivity of coronaviruses observed in 293T cells afforded the opportunity to investigate whether efficiency of entry inhibition by IFITMs and endosomal cholesterol accumulation correlate. No such correlation was observed. Furthermore, entry mediated by the influenza virus hemagglutinin was robustly inhibited by IFITM3 but was insensitive to accumulation of endosomal cholesterol, indicating that modulation of cholesterol synthesis/transport did not account for the antiviral activity of IFITM3. Collectively, these results show that the emerging MERS-CoV is a target of the antiviral activity of IFITM proteins and demonstrate that mechanisms other than accumulation of endosomal cholesterol can contribute to viral entry inhibition by IFITMs.",2014 Sep 26,"['Wrensch, Florian', 'Winkler, Michael', 'Pöhlmann, Stefan']",Viruses,,,True
d8271398b9073fbb1ad449e72697e6ae8f71d3d8,PMC,Passive Broad-Spectrum Influenza Immunoprophylaxis,http://dx.doi.org/10.1155/2014/267594,PMC4190013,25328697,CC BY,"Influenza is a perennial problem affecting millions of people annually with the everpresent threat of devastating pandemics. Active prophylaxis by vaccination against influenza virus is currently the main countermeasure supplemented with antivirals. However, disadvantages of this strategy include the impact of antigenic drift, necessitating constant updating of vaccine strain composition, and emerging antiviral drug resistance. The development of other options for influenza prophylaxis, particularly with broad acting agents able to provide protection in the period between the onset of a pandemic and the development of a strain specific vaccine, is of great interest. Exploitation of broad-spectrum mediators could provide barricade protection in the early critical phase of influenza virus outbreaks. Passive immunity has the potential to provide immediate antiviral effects, inhibiting virus replication, reducing virus shedding, and thereby protecting vulnerable populations in the event of an impending influenza pandemic. Here, we review passive broad-spectrum influenza prophylaxis options with a focus on harnessing natural host defenses, including interferons and antibodies.",2014 Sep 22,"['Berry, Cassandra M.', 'Penhale, William J.', 'Sangster, Mark Y.']",Influenza Res Treat,,,True
f5df82125769765004c7dd11f066688e6dc3cc76,PMC,Regulation of TGF-β Signal Transduction,http://dx.doi.org/10.1155/2014/874065,PMC4190275,25332839,CC BY,"Transforming growth factor-β (TGF-β) signaling regulates diverse cellular processes, including cell proliferation, differentiation, apoptosis, cell plasticity, and migration. TGF-β signaling can be mediated by Smad proteins or other signaling proteins such as MAP kinases and Akt. TGF-β signaling is tightly regulated at different levels along the pathways to ensure its proper physiological functions in different cells and tissues. Deregulation of TGF-β signaling has been associated with various kinds of diseases, such as cancer and tissue fibrosis. This paper focuses on our recent work on regulation of TGF-β signaling.",2014 Sep 23,"['Zhao, Bing', 'Chen, Ye-Guang']",Scientifica (Cairo),,,True
19e9c8796df362aa81ecfabf7730cfa4df5e5be6,PMC,Establishment of Myotis myotis Cell Lines - Model for Investigation of Host-Pathogen Interaction in a Natural Host for Emerging Viruses,http://dx.doi.org/10.1371/journal.pone.0109795,PMC4190323,25295526,CC BY,"Bats are found to be the natural reservoirs for many emerging viruses. In most cases, severe clinical signs caused by such virus infections are normally not seen in bats. This indicates differences in the virus-host interactions and underlines the necessity to develop natural host related models to study these phenomena. Due to the strict protection of European bat species, immortalized cell lines are the only alternative to investigate the innate anti-virus immune mechanisms. Here, we report about the establishment and functional characterization of Myotis myotis derived cell lines from different tissues: brain (MmBr), tonsil (MmTo), peritoneal cavity (MmPca), nasal epithelium (MmNep) and nervus olfactorius (MmNol) after immortalization by SV 40 large T antigen. The usefulness of these cell lines to study antiviral responses has been confirmed by analysis of their susceptibility to lyssavirus infection and the mRNA patterns of immune-relevant genes after poly I:C stimulation. Performed experiments indicated varying susceptibility to lyssavirus infection with MmBr being considerably less susceptible than the other cell lines. Further investigation demonstrated a strong activation of interferon mediated antiviral response in MmBr contributing to its resistance. The pattern recognition receptors: RIG-I and MDA5 were highly up-regulated during rabies virus infection in MmBr, suggesting their involvement in promotion of antiviral responses. The presence of CD14 and CD68 in MmBr suggested MmBr cells are microglia-like cells which play a key role in host defense against infections in the central nervous system (CNS). Thus the expression pattern of MmBr combined with the observed limitation of lyssavirus replication underpin a protective mechanism of the CNS controlling the lyssavirus infection. Overall, the established cell lines are important tools to analyze antiviral innate immunity in M. myotis against neurotropic virus infections and present a valuable tool for a broad spectrum of future investigations in cellular biology of M. myotis.",2014 Oct 8,"['He, Xiaocui', 'Korytář, Tomáš', 'Zhu, Yaqing', 'Pikula, Jiří', 'Bandouchova, Hana', 'Zukal, Jan', 'Köllner, Bernd']",PLoS One,,,True
7a6456acf2a0eda491acf31d4887daf43a25ca27,PMC,"Comparative pathology of pigs infected with Korean H1N1, H1N2, or H3N2 swine influenza A viruses",http://dx.doi.org/10.1186/1743-422X-11-170,PMC4190492,25253051,CC BY,"BACKGROUND: The predominant subtypes of swine influenza A virus (SIV) in Korea swine population are H1N1, H1N2, and H3N2. The viruses are genetically close to the classical U.S. H1N1 and triple-reassortant H1N2 and H3N2 viruses, respectively. Comparative pathogenesis caused by Korean H1N1, H1N2, and H3N2 SIV was evaluated in this study. FINDINGS: The H3N2 infected pigs had severe scores of gross and histopathological lesions at post-inoculation days (PID) 2, and this then progressively decreased. Both the H1N1 and H1N2 infected pigs lacked gross lesions at PID 2, but they showed moderate to severe pneumonia on PID 4, 7 and 14. The pigs infected with H1N1 had significant scores of gross and histopathological lesions when compared with the other pigs infected with H1N2, H3N2, and mock at PID 14. Mean SIV antigen-positive scores were rarely detected for pigs infected with H1N2 and H3N2 from PID 7, whereas a significantly increased amount of viral antigens were found in the bronchioles and alveolar epithelium of the H1N1infected pigs at PID 14. CONCLUSIONS: We demonstrated that Korean SIV subtypes had different pulmonary pathologic patterns. The Korean H3N2 rapidly induced acute lung lesions such as broncho-interstitial pneumonia, while the Korean H1N1 showed longer course of infection as compared to other strains.",2014 Sep 24,"['Lyoo, Kwang-Soo', 'Kim, Jeong-Ki', 'Jung, Kwonil', 'Kang, Bo-Kyu', 'Song, Daesub']",Virol J,,,True
aa14d6de32495ec579e30a5c6f1ae21666c01c8a,PMC,Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives,http://dx.doi.org/10.3390/pharmaceutics6030378,PMC4190526,25014738,CC BY,"Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT). Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV) etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents.",2014 Jul 10,"['Xu, Yingying', 'Yuen, Pak-Wai', 'Lam, Jenny Ka-Wing']",Pharmaceutics,,,True
7be0bfff671903d1176a2da34f16f1ff8189b554,PMC,The methyltransferase domain of dengue virus protein NS5 ensures efficient RNA synthesis initiation and elongation by the polymerase domain,http://dx.doi.org/10.1093/nar/gku666,PMC4191377,25209234,CC BY,"Viral RNA-dependent RNA polymerases (RdRps) responsible for the replication of single-strand RNA virus genomes exert their function in the context of complex replication machineries. Within these replication complexes the polymerase activity is often highly regulated by RNA elements, proteins or other domains of multi-domain polymerases. Here, we present data of the influence of the methyltransferase domain (NS5-MTase) of dengue virus (DENV) protein NS5 on the RdRp activity of the polymerase domain (NS5-Pol). The steady-state polymerase activities of DENV-2 recombinant NS5 and NS5-Pol are compared using different biochemical assays allowing the dissection of the de novo initiation, transition and elongation steps of RNA synthesis. We show that NS5-MTase ensures efficient RdRp activity by stimulating the de novo initiation and the elongation phase. This stimulation is related to a higher affinity of NS5 toward the single-strand RNA template indicating NS5-MTase either completes a high-affinity RNA binding site and/or promotes the correct formation of the template tunnel. Furthermore, the NS5-MTase increases the affinity of the priming nucleotide ATP upon de novo initiation and causes a higher catalytic efficiency of the polymerase upon elongation. The complex stimulation pattern is discussed under the perspective that NS5 adopts several conformations during RNA synthesis.",2014 Oct 13,"['Potisopon, Supanee', 'Priet, Stéphane', 'Collet, Axelle', 'Decroly, Etienne', 'Canard, Bruno', 'Selisko, Barbara']",Nucleic Acids Res,,,True
d307fc598aa1ad8f3c3480d20a996a23698cb57d,PMC,The methyltransferase domain of dengue virus protein NS5 ensures efficient RNA synthesis initiation and elongation by the polymerase domain,http://dx.doi.org/10.1093/nar/gku666,PMC4191377,25209234,CC BY,"Viral RNA-dependent RNA polymerases (RdRps) responsible for the replication of single-strand RNA virus genomes exert their function in the context of complex replication machineries. Within these replication complexes the polymerase activity is often highly regulated by RNA elements, proteins or other domains of multi-domain polymerases. Here, we present data of the influence of the methyltransferase domain (NS5-MTase) of dengue virus (DENV) protein NS5 on the RdRp activity of the polymerase domain (NS5-Pol). The steady-state polymerase activities of DENV-2 recombinant NS5 and NS5-Pol are compared using different biochemical assays allowing the dissection of the de novo initiation, transition and elongation steps of RNA synthesis. We show that NS5-MTase ensures efficient RdRp activity by stimulating the de novo initiation and the elongation phase. This stimulation is related to a higher affinity of NS5 toward the single-strand RNA template indicating NS5-MTase either completes a high-affinity RNA binding site and/or promotes the correct formation of the template tunnel. Furthermore, the NS5-MTase increases the affinity of the priming nucleotide ATP upon de novo initiation and causes a higher catalytic efficiency of the polymerase upon elongation. The complex stimulation pattern is discussed under the perspective that NS5 adopts several conformations during RNA synthesis.",2014 Oct 13,"['Potisopon, Supanee', 'Priet, Stéphane', 'Collet, Axelle', 'Decroly, Etienne', 'Canard, Bruno', 'Selisko, Barbara']",Nucleic Acids Res,,,False
51e10bb6f0ef0363cab568d94c52db244ce7ad1f,PMC,"Seasonal Variation of Newly Notified Pulmonary Tuberculosis Cases from 2004 to 2013 in Wuhan, China",http://dx.doi.org/10.1371/journal.pone.0108369,PMC4193739,25303675,CC BY,"BACKGROUND: Although there was a report about the seasonal variation in Wuhan city, it only analyzed the prevalence data of pulmonary tuberculosis (TB) cases, and just studied the seasonality by subgroup of smear positive and negative from 2006 to 2010 by spectral analysis. In this study, we investigated the seasonality of the total newly notified pulmonary TB cases by subgroups such as time period, sex, age, occupation, district, and sputum smear result from 2004 to 2013 in Wuhan by a popular seasonal adjustment model (TRAMO-SEATS). METHODS: Monthly pulmonary TB cases from 2004 to 2013 in Wuhan were analyzed by the TRAMO-SEATS seasonal adjustment program. Seasonal amplitude was calculated and compared within the subgroups. RESULTS: From 2004 to 2013, there were 77.76 thousand newly notified pulmonary TB cases in Wuhan, China. There was a dominant peak spring peak (March) with seasonal amplitude of 56.81% and a second summer peak (September) of 43.40%, compared with the trough month (December). The spring seasonal amplitude in 2004–2008 was higher than that of 2009–2013(P<0.05). There were no statistical differences for spring seasonal amplitude within subgroups of gender, age, district, and sputum smear result (P>0.05). However, there were significant differences in spring seasonal amplitude by occupation, with amplitude ranging from 59.37% to 113.22% (P<0.05). The summer seasonal amplitude in 2004–2008 was higher than that of 2009–2013(P<0.05). There were no statistical differences in summer seasonal amplitude within subgroups of gender, district, sputum smear result(P>0.05). There were significant differences in summer seasonal amplitude by age, with amplitude ranging from 36.05% to 100.09% (P<0.05). Also, there were significant differences in summer seasonal amplitude by occupation, with amplitude ranging from 43.40% to 109.88% (P<0.05). CONCLUSIONS: There was an apparent seasonal variation in pulmonary TB cases in Wuhan. We speculated that spring peak in our study was most likely caused by the increased reactivation of the latent TB due to vitamin D deficiency and high PM2.5 concentration, while the summer peak was mainly resulted from the enhanced winter transmission due to indoor crowding in winter, overcrowding of public transportation over the period of the Spring Festival and health care seeking delay in winter.",2014 Oct 10,"['Yang, Xiaobing', 'Duan, Qionghong', 'Wang, Jianjie', 'Zhang, Zhengbin', 'Jiang, Gaofeng']",PLoS One,,,True
0a3ef8eca5d6cd4d7a0fef83335cc02a2347492c,PMC,Rapid Isolation of Antibody from a Synthetic Human Antibody Library by Repeated Fluorescence-Activated Cell Sorting (FACS),http://dx.doi.org/10.1371/journal.pone.0108225,PMC4193741,25303314,CC BY,"Antibodies and their derivatives are the most important agents in therapeutics and diagnostics. Even after the significant progress in the technology for antibody screening from huge libraries, it takes a long time to isolate an antibody, which prevents a prompt action against the spread of a disease. Here, we report a new strategy for isolating desired antibodies from a combinatorial library in one day by repeated fluorescence-activated cell sorting (FACS). First, we constructed a library of synthetic human antibody in which single-chain variable fragment (scFv) was expressed in the periplasm of Escherichia coli. After labeling the cells with fluorescent antigen probes, the highly fluorescent cells were sorted by using a high-speed cell sorter, and these cells were reused without regeneration in the next round of sorting. After repeating this sorting, the positive clones were completely enriched in several hours. Thus, we screened the library against three viral antigens, including the H1N1 influenza virus, Hepatitis B virus, and Foot-and-mouth disease virus. Finally, the potential antibody candidates, which show K(D) values between 10 and 100 nM against the target antigens, could be successfully isolated even though the library was relatively small (∼10(6)). These results show that repeated FACS screening without regeneration of the sorted cells can be a powerful method when a rapid response to a spreading disease is required.",2014 Oct 10,"['Yim, Sung Sun', 'Bang, Hyun Bae', 'Kim, Young Hwan', 'Lee, Yong Jae', 'Jeong, Gu Min', 'Jeong, Ki Jun']",PLoS One,,,True
50f42123b5035f840369d0ff88cc55263a1394b7,PMC,The interconnected and cross-border nature of risks posed by infectious diseases,http://dx.doi.org/10.3402/gha.v7.25287,PMC4195207,25308818,CC BY,"Infectious diseases can constitute public health emergencies of international concern when a pathogen arises, acquires new characteristics, or is deliberately released, leading to the potential for loss of human lives as well as societal disruption. A wide range of risk drivers are now known to lead to and/or exacerbate the emergence and spread of infectious disease, including global trade and travel, the overuse of antibiotics, intensive agriculture, climate change, high population densities, and inadequate infrastructures, such as water treatment facilities. Where multiple risk drivers interact, the potential impact of a disease outbreak is amplified. The varying temporal and geographic frequency with which infectious disease events occur adds yet another layer of complexity to the issue. Mitigating the emergence and spread of infectious disease necessitates mapping and prioritising the interdependencies between public health and other sectors. Conversely, during an international public health emergency, significant disruption occurs not only to healthcare systems but also to a potentially wide range of sectors, including trade, tourism, energy, civil protection, transport, agriculture, and so on. At the same time, dealing with a disease outbreak may require a range of critical sectors for support. There is a need to move beyond narrow models of risk to better account for the interdependencies between health and other sectors so as to be able to better mitigate and respond to the risks posed by emerging infectious disease.",2014 Oct 10,"['Suk, Jonathan E.', 'Van Cangh, Thomas', 'Beauté, Julien', 'Bartels, Cornelius', 'Tsolova, Svetla', 'Pharris, Anastasia', 'Ciotti, Massimo', 'Semenza, Jan C.']",Glob Health Action,,,True
db361f98f584f900325b649f3ffa0e8057d0f20c,PMC,Alterations in Nerve-Evoked Bladder Contractions in a Coronavirus-Induced Mouse Model of Multiple Sclerosis,http://dx.doi.org/10.1371/journal.pone.0109314,PMC4195612,25310403,CC BY,"BACKGROUND: Patients with neurodegenerative diseases such as multiple sclerosis, Parkinson’s, and Alzheimer’s often present with lower urinary tract symptoms (LUTS, urinary frequency, urgency, nocturia and retention) resulting from damage to the peripheral and central nervous systems. These studies were designed to examine the changes in the function of the bladder that may underlie neurogenic bladder dysfunction using a mouse model of demyelination in the CNS. METHODS: Bladders from 12 week old male C57BL/6J mice with coronavirus-induced encephalomyelitis (CIE, a chronic, progressive demyelinating disease model of human MS), and age-matched controls, were cut into 5–7 strips and suspended in physiological muscle baths for tension measurement in response to agonists and electric field stimulation (EFS). Experiments were performed on intact and denuded (with mucosa removed) bladder strips. RESULTS: The maximum effect of EFS was not significantly different between CIE and control bladders. Nerve-evoked EFS contractions (tetrodotoxin-sensitive) were blocked by a combination of atropine (cholinergic antagonist) and α,β-methylene ATP (an ATP analog that desensitizes purinergic receptors). In response to EFS, the α,β-methylene ATP-resistant (cholinergic) component of contraction was significantly reduced, while the atropine-resistant (purinergic) component was significantly increased in CIE bladders. Removal of the mucosa in CIE bladders restored the cholinergic component. Bethanechol (muscarinic receptor agonist) potency was significantly increased in CIE bladders. CONCLUSIONS: Our data demonstrate a deficit in the nerve-evoked cholinergic component of contraction that is not due to the ability of the smooth muscle to respond to acetylcholine. We conclude that neurodegenerative bladder dysfunction in this model of multiple sclerosis may be due, in part, to pathologic changes in the mucosa that causes suppression of muscarinic receptor-mediated contractile response and augmentation of purinergic response of the underlying muscle. Further studies utilizing CIE mice should help elucidate the pathological changes in the mucosa resulting from demyelination in the CNS.",2014 Oct 13,"['Lamarre, Neil S.', 'Braverman, Alan S.', 'Malykhina, Anna P.', 'Barbe, Mary F.', 'Ruggieri, Michael R.']",PLoS One,,,True
ffd640ccc48cf505cf385e2a7ab7d2720e3ec427,PMC,Review: The Important Bacterial Zoonoses in “One Health” Concept,http://dx.doi.org/10.3389/fpubh.2014.00144,PMC4196475,25353010,CC BY,"An infectious disease that is transmitted from animals to humans, sometimes by a vector, is called zoonosis. The focus of this review article is on the most common emerging and re-emerging bacterial zoonotic diseases. The role of “One Health” approach, public health education, and some measures that can be taken to prevent zoonotic bacterial infections are discussed. Key points: A zoonotic bacterial disease is a disease that can be very commonly transmitted between animals and humans. Global climate changes, overuse of antimicrobials in medicine, more intensified farm settings, and closer interactions with animals facilitate emergence or re-emergence of bacterial zoonotic infections. The global “One Health” approach, which requires interdisciplinary collaborations and communications in all aspects of health care for humans, animals, and the environment, will support public health in general. New strategies for continuous dissemination of multidisciplinary research findings related to zoonotic bacterial diseases are hence needed.",2014 Oct 14,"['Cantas, Leon', 'Suer, Kaya']",Front Public Health,,,True
ae88cd3f2ac21948c74fd7b15b62cc03e9bac235,PMC,Verifying the Stability of Selected Genes for Normalization in Q PCR Experiments of Spodoptera frugiperda Cells during AcMNPV Infection,http://dx.doi.org/10.1371/journal.pone.0108516,PMC4196776,25313905,CC BY,"It is challenging to find genes with stable transcripts for use as reference genes for quantitative realtime polymerase chain reaction (qRT-PCR) during viral infection. Autographa californica nucleopolyhedrovirus (AcMNPV) is known to globally shut off host gene transcription in Sf21 cells and to modify their cytoskeletons. In this study, seven host genes were selected for validation as references for gene expression experiments using qRT-PCR. Two of them, ecdysoneless (ECD) and myosin showed stable RNA levels in our previous microarray study at 6, 12, and 24 hpi for both genes and 48 hpi for ECD. The others, actin, tubulin, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and 28S ribosome (28S), are commonly employed as reference genes for qRT-PCR. Ribosomal protein L35 (L35) gene was selected to test if ribosomal protein genes show stable RNA transcript levels similar to 28S and 18S rRNA and to validate the microarray data. In addition to 28S, previously known to have stable transcript levels, qRT-PCR showed that ECD transcript levels remained constant throughout the time course of AcMNPV infection. Transcripts of cytoskeleton genes such as actin, tubulin, and myosin declined dramatically as the infection progressed. GAPDH and L35 transcripts also declined over time. These results indicate that ECD is a reliable reference gene for qRT-PCR experiments during AcMNPV infection of Spodoptera frugiperda cells. Although 28S could be used as a reference gene for these experiments, it is less useful than ECD because of its abundance, which might make it difficult to establish an accurate baseline value for data analysis.",2014 Oct 14,"['Salem, Tamer Z.', 'Allam, Walaa R.', 'Thiem, Suzanne M.']",PLoS One,,,True
1a0304e5340ef8d016dd2f73d730072c2559acbb,PMC,Interleukin-1β Induces Blood–Brain Barrier Disruption by Downregulating Sonic Hedgehog in Astrocytes,http://dx.doi.org/10.1371/journal.pone.0110024,PMC4196962,25313834,CC BY,"The blood–brain barrier (BBB) is composed of capillary endothelial cells, pericytes, and perivascular astrocytes, which regulate central nervous system homeostasis. Sonic hedgehog (SHH) released from astrocytes plays an important role in the maintenance of BBB integrity. BBB disruption and microglial activation are common pathological features of various neurologic diseases such as multiple sclerosis, Parkinson’s disease, amyotrophic lateral sclerosis, and Alzheimer’s disease. Interleukin-1β (IL-1β), a major pro-inflammatory cytokine released from activated microglia, increases BBB permeability. Here we show that IL-1β abolishes the protective effect of astrocytes on BBB integrity by suppressing astrocytic SHH production. Astrocyte conditioned media, SHH, or SHH signal agonist strengthened BBB integrity by upregulating tight junction proteins, whereas SHH signal inhibitor abrogated these effects. Moreover, IL-1β increased astrocytic production of pro-inflammatory chemokines such as CCL2, CCL20, and CXCL2, which induce immune cell migration and exacerbate BBB disruption and neuroinflammation. Our findings suggest that astrocytic SHH is a potential therapeutic target that could be used to restore disrupted BBB in patients with neurologic diseases.",2014 Oct 14,"['Wang, Yue', 'Jin, Shijie', 'Sonobe, Yoshifumi', 'Cheng, Yi', 'Horiuchi, Hiroshi', 'Parajuli, Bijay', 'Kawanokuchi, Jun', 'Mizuno, Tetsuya', 'Takeuchi, Hideyuki', 'Suzumura, Akio']",PLoS One,,,True
8ae561e754ff3e094cd9d1e92f8517f8f9f4506a,PMC,IFITM3 Polymorphism rs12252-C Restricts Influenza A Viruses,http://dx.doi.org/10.1371/journal.pone.0110096,PMC4196997,25314048,CC BY,"The IFITM3 polymorphism rs12252-C, which encodes an IFITM3 isoform (Δ21 IFITM3) lacking 21 amino acids at the amino terminus, has been controversially associated with poor clinical outcomes in patients with H1N1 influenza A virus (IAV) infections. In vitro studies have shown that Δ21 IFITM3 loses its ability to restrict H1N1 IAV. Subsequent research has also revealed that tyrosine 20 is the key determinant for IFITM3 endocytic trafficking, which is essential for the efficient anti-viral activity of IFITM3. In contrast to previous studies, we demonstrated that both Δ21 IFITM3 and an IFITM3 variant (Y20A IFITM3), in which tyrosine 20 is substituted with alanine, strongly restricted entry mediated by IAV H1, H3, H5, and H7 proteins. Δ21 IFITM3 also efficiently suppressed replication of H1N1 and, to a lesser extent, H3N2 IAV. Δ21 IFITM3 and Y20A IFITM3 had broader subcellular distributions than full-length IFITM3 but an abundant amount of both IFITM3 variants still localized to late endosomes and lysosomes. Our data indicate that tyrosine 20 partially regulates the subcellular localization of IFITM3 but is not functionally essential for IFITM3-mediated IAV restriction. They also suggested that mechanisms, other than viral entry restriction, might contribute to variations in clinical outcomes of H1N1 influenza associated with rs12252-C.",2014 Oct 14,"['Williams, David Evan Joseph', 'Wu, Wan-Lin', 'Grotefend, Christopher Robert', 'Radic, Vladimir', 'Chung, Changik', 'Chung, Young-Hwa', 'Farzan, Michael', 'Huang, I-Chueh']",PLoS One,,,True
e2b3cf2cab4bdb3f5d357c987852c829cb4f6995,PMC,The limits of global health diplomacy: Taiwan’s observer status at the world health assembly,http://dx.doi.org/10.1186/s12992-014-0071-y,PMC4197227,25270977,CC BY,"In 2009, health authorities from Taiwan (under the name “Chinese Taipei”)(a) formally attended the 62(nd) World Health Assembly (WHA) of the World Health Organization as observers, marking the country’s participation for the first time since 1972. The long process of negotiating this breakthrough has been cited as an example of successful global health diplomacy. This paper analyses this negotiation process, drawing on government documents, formal representations from both sides of the Taiwan Strait, and key informant interviews. The actors and their motivations, along with the forums, practices and outcomes of the negotiation process, are detailed. While it is argued that non-traditional diplomatic action was important in establishing the case for Taiwan’s inclusion at the WHA, traditional concerns regarding Taiwanese sovereignty and diplomatic representation ultimately played a decisive role. The persistent influence of these traditional diplomatic questions illustrates the limits of global health diplomacy.",2014 Oct 1,"['Herington, Jonathan', 'Lee, Kelley']",Global Health,,,True
6eb145a990b1132457f78c4e1521ab827b715ad0,PMC,A Beneficiary Role for Neuraminidase in Influenza Virus Penetration through the Respiratory Mucus,http://dx.doi.org/10.1371/journal.pone.0110026,PMC4198190,25333824,CC BY,"Swine influenza virus (SIV) has a strong tropism for pig respiratory mucosa, which consists of a mucus layer, epithelium, basement membrane and lamina propria. Sialic acids present on the epithelial surface have long been considered to be determinants of influenza virus tropism. However, mucus which is also rich in sialic acids may serve as the first barrier of selection. It was investigated how influenza virus interacts with the mucus to infect epithelial cells. Two techniques were applied to track SIV H1N1 in porcine mucus. The microscopic diffusion of SIV particles in the mucus was analyzed by single particle tracking (SPT), and the macroscopic penetration of SIV through mucus was studied by a virus in-capsule-mucus penetration system, followed by visualizing the translocation of the virions with time by immunofluorescence staining. Furthermore, the effects of neuraminidase on SIV getting through or binding to the mucus were studied by using zanamivir, a neuraminidase inhibitor (NAI), and Arthrobacter ureafaciens neuraminidase. The distribution of the diffusion coefficient shows that 70% of SIV particles were entrapped, while the rest diffused freely in the mucus. Additionally, SIV penetrated the porcine mucus with time, reaching a depth of 65 µm at 30 min post virus addition, 2 fold of that at 2 min. Both the microscopic diffusion and macroscopic penetration were largely diminished by NAI, while were clearly increased by the effect of exogenous neuraminidase. Moreover, the exogenous neuraminidase sufficiently prevented the binding of SIV to mucus which was reversely enhanced by effect of NAI. These findings clearly show that the neuraminidase helps SIV move through the mucus, which is important for the virus to reach and infect epithelial cells and eventually become shed into the lumen of the respiratory tract.",2014 Oct 15,"['Yang, Xiaoyun', 'Steukers, Lennert', 'Forier, Katrien', 'Xiong, Ranhua', 'Braeckmans, Kevin', 'Van Reeth, Kristien', 'Nauwynck, Hans']",PLoS One,,,True
43c296a219a62ac9f9a632490034b6fdfc7b871e,PMC,Intestinal current measurement versus nasal potential difference measurements for diagnosis of cystic fibrosis: a case–control study,http://dx.doi.org/10.1186/1471-2466-14-156,PMC4199064,25280757,CC BY,"BACKGROUND: Nasal potential difference (NPD) and intestinal current measurement (ICM) are functional CFTR tests that are used as adjunctive diagnostic tools for cystic fibrosis (CF). Smoking has a systemic negative impact on CFTR function. A diagnostic comparison between NPD and ICM and the impact of smoking on both CFTR tests has not been done. METHODS: The sweat chloride test, NPD, and ICM were performed in 18 patients with CF (sweat chloride >60 mmol/l), including 6 pancreatic sufficient (PS) patients, and 13 healthy controls, including 8 smokers. The NPD CFTR response to Cl-free and isoproterenol perfusion (Δ0Cl(-) + Iso) was compared to the ICM CFTR response to forskolin/IBMX, carbachol, and histamine (ΔI(sc, forskolin/IBMX+ carbachol+histamine)). RESULTS: The mean NPD CFTR response and ICM CFTR response between patients with CF and healthy controls was significantly different (p <0.001), but not between patients with CF who were PS and those who were pancreatic insufficient (PI). Smokers have a decreased CFTR response measured by NPD (p = 0.049). For ICM there is a trend towards decreased CFTR response (NS). Three healthy control smokers had NPD responses within the CF-range. In contrast to NPD, there was no overlap of the ICM response between patients with CF and controls. CONCLUSIONS: ICM is superior to NPD in distinguishing between patients with CF who have a sweat chloride > 60 mmol/l and healthy controls, including smokers. Neither NPD nor ICM differentiated between patients with CF who were PS from those who were PI. Smoking has a negative impact on CFTR function in healthy controls measured by NPD and challenges the diagnostic interpretation of NPD, but not ICM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2466-14-156) contains supplementary material, which is available to authorized users.",2014 Oct 4,"['Bagheri-Hanson, Azadeh', 'Nedwed, Sebastian', 'Rueckes-Nilges, Claudia', 'Naehrlich, Lutz']",BMC Pulm Med,,,True
595f2518368eb7c7c56b8669bcf66978ac636ad1,PMC,Antibody-Validated Proteins in Inflamed Islets of Fulminant Type 1 Diabetes Profiled by Laser-Capture Microdissection Followed by Mass Spectrometry,http://dx.doi.org/10.1371/journal.pone.0107664,PMC4199548,25329145,CC BY,"BACKGROUND: There are no reports of proteomic analyses of inflamed islets in type 1 diabetes. PROCEDURES: Proteins expressed in the islets of enterovirus-associated fulminant type 1 diabetes (FT1DM) with extensive insulitis were identified by laser-capture microdissection mass spectrometry using formalin-fixed paraffin-embedded pancreatic tissues. RESULTS: Thirty-eight proteins were identified solely in FT1DM islets, most of which have not been previously linked to type 1 diabetes. Five protein-protein interacting clusters were identified, and the cellular localization of selected proteins was validated immunohistochemically. Migratory activity-related proteins, including plastin-2 (LCP1), moesin (MSN), lamin-B1 (LMNB1), Ras GTPase-activating-like protein (IQGAP1) and others, were identified in CD8(+) T cells and CD68(+) macrophages infiltrated to inflamed FT1DM islets. Proteins involved in successive signaling in innate/adaptive immunity were identified, including SAM domain and HD domain-containing protein 1 (SAMHD1), Ras GTPase-activating-like protein (IQGAP1), proteasome activator complex subunit 1 (PSME1), HLA class I histocompatibility antigen (HLA-C), and signal transducer and activator of transcription 1-alpha/beta (STAT1). Angiogenic (thymidine phosphorylase (TYMP)) and anti-angiogenic (tryptophan-tRNA ligase (WARS)) factors were identified in migrating CD8(+) T cells and CD68(+) macrophages. Proteins related to virus replication and cell proliferation, including probable ATP-dependent RNA helicase DEAD box helicase 5 (DDX5) and heterogeneous nuclear ribonucleoprotein H (HNRNPH1), were identified. The anti-apoptotic protein T-complex protein 1 subunit epsilon (CCT5), the anti-oxidative enzyme 6-phosphogluconate dehydrogenase (PDG), and the anti-viral and anti-apoptotic proteins serpin B6 (SERPINB6) and heat shock 70 kDa protein1-like (HSPA1L), were identified in FT1DM-affected islet cells. CONCLUSION: The identified FT1DM-characterizing proteins include those involved in aggressive beta cell destruction through massive immune cell migration and proteins involved in angiogenesis and islet vasculature bleeding, cell repair, and anti-inflammatory processes. Several target proteins for future type 1 diabetes interventions were identified.",2014 Oct 16,"['Nishida, Yoriko', 'Aida, Kaoru', 'Kihara, Makoto', 'Kobayashi, Tetsuro']",PLoS One,,,True
0c0e91904a6c84a7ee80cc69fe83370aaa3ca708,PMC,"Travel-related MERS-CoV cases: an assessment of exposures and risk factors in a group of Dutch travellers returning from the Kingdom of Saudi Arabia, May 2014",http://dx.doi.org/10.1186/1742-7622-11-16,PMC4200475,25328533,CC BY,"BACKGROUND: In May 2014, Middle East respiratory syndrome coronavirus (MERS-CoV) infection, with closely related viral genomes, was diagnosed in two Dutch residents, returning from a pilgrimage to Medina and Mecca, Kingdom of Saudi Arabia (KSA). These patients travelled with a group of 29 other Dutch travellers. We conducted an epidemiological assessment of the travel group to identify likely source(s) of infection and presence of potential risk factors. METHODS: All travellers, including the two cases, completed a questionnaire focussing on potential human, animal and food exposures to MERS-CoV. The questionnaire was modified from the WHO MERS-CoV questionnaire, taking into account the specific route and activities of the travel group. RESULTS: Twelve non-cases drank unpasteurized camel milk and had contact with camels. Most travellers, including one of the two patients (Case 1), visited local markets, where six of them consumed fruits. Two travellers, including Case 1, were exposed to coughing patients when visiting a hospital in Medina. Four travellers, including Case 1, visited two hospitals in Mecca. All travellers had been in contact with Case 1 while he was sick, with initially non-respiratory complaints. The cases were found to be older than the other travellers and both had co-morbidities. CONCLUSIONS: This epidemiological study revealed the complexity of MERS-CoV outbreak investigations with multiple potential exposures to MERS-CoV reported such as healthcare visits, camel exposure, and exposure to untreated food products. Exposure to MERS-CoV during a hospital visit is considered a likely source of infection for Case 1 but not for Case 2. For Case 2, the most likely source could not be determined. Exposure to MERS-CoV via direct contact with animals or dairy products seems unlikely for the two Dutch cases. Furthermore, exposure to a common but still unidentified source cannot be ruled out. More comprehensive research into sources of infection in the Arabian Peninsula is needed to strengthen and specify the prevention of MERS-CoV infections.",2014 Oct 17,"['Fanoy, Ewout B', 'van der Sande, Marianne AB', 'Kraaij-Dirkzwager, Marleen', 'Dirksen, Kees', 'Jonges, Marcel', 'van der Hoek, Wim', 'Koopmans, Marion PG', 'van der Werf, Douwe', 'Sonder, Gerard', 'van der Weijden, Charlie', 'van der Heuvel, Jet', 'Gelinck, Luc', 'Bouwhuis, Jolande W', 'van Gageldonk-Lafeber, Arianne B']",Emerg Themes Epidemiol,,,True
c4bddec0b339a9f5ea397a7390327d12c72159a2,PMC,Adaptive Management and the Value of Information: Learning Via Intervention in Epidemiology,http://dx.doi.org/10.1371/journal.pbio.1001970,PMC4204804,25333371,CC0,"Optimal intervention for disease outbreaks is often impeded by severe scientific uncertainty. Adaptive management (AM), long-used in natural resource management, is a structured decision-making approach to solving dynamic problems that accounts for the value of resolving uncertainty via real-time evaluation of alternative models. We propose an AM approach to design and evaluate intervention strategies in epidemiology, using real-time surveillance to resolve model uncertainty as management proceeds, with foot-and-mouth disease (FMD) culling and measles vaccination as case studies. We use simulations of alternative intervention strategies under competing models to quantify the effect of model uncertainty on decision making, in terms of the value of information, and quantify the benefit of adaptive versus static intervention strategies. Culling decisions during the 2001 UK FMD outbreak were contentious due to uncertainty about the spatial scale of transmission. The expected benefit of resolving this uncertainty prior to a new outbreak on a UK-like landscape would be £45–£60 million relative to the strategy that minimizes livestock losses averaged over alternate transmission models. AM during the outbreak would be expected to recover up to £20.1 million of this expected benefit. AM would also recommend a more conservative initial approach (culling of infected premises and dangerous contact farms) than would a fixed strategy (which would additionally require culling of contiguous premises). For optimal targeting of measles vaccination, based on an outbreak in Malawi in 2010, AM allows better distribution of resources across the affected region; its utility depends on uncertainty about both the at-risk population and logistical capacity. When daily vaccination rates are highly constrained, the optimal initial strategy is to conduct a small, quick campaign; a reduction in expected burden of approximately 10,000 cases could result if campaign targets can be updated on the basis of the true susceptible population. Formal incorporation of a policy to update future management actions in response to information gained in the course of an outbreak can change the optimal initial response and result in significant cost savings. AM provides a framework for using multiple models to facilitate public-health decision making and an objective basis for updating management actions in response to improved scientific understanding.",2014 Oct 21,"['Shea, Katriona', 'Tildesley, Michael J.', 'Runge, Michael C.', 'Fonnesbeck, Christopher J.', 'Ferrari, Matthew J.']",PLoS Biol,,,True
02766b20eeb39ff051a2f110def2e4bf8b9b010b,PMC,Proteome Profile of Swine Testicular Cells Infected with Porcine Transmissible Gastroenteritis Coronavirus,http://dx.doi.org/10.1371/journal.pone.0110647,PMC4204940,25333634,CC BY,"The interactions occurring between a virus and a host cell during a viral infection are complex. The purpose of this paper was to analyze altered cellular protein levels in porcine transmissible gastroenteritis coronavirus (TGEV)-infected swine testicular (ST) cells in order to determine potential virus-host interactions. A proteomic approach using isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography-tandem mass spectrometry identification was conducted on the TGEV-infected ST cells. The results showed that the 4-plex iTRAQ-based quantitative approach identified 4,112 proteins, 146 of which showed significant changes in expression 48 h after infection. At 64 h post infection, 219 of these proteins showed significant change, further indicating that a larger number of proteomic changes appear to occur during the later stages of infection. Gene ontology analysis of the altered proteins showed enrichment in multiple biological processes, including cell adhesion, response to stress, generation of precursor metabolites and energy, cell motility, protein complex assembly, growth, developmental maturation, immune system process, extracellular matrix organization, locomotion, cell-cell signaling, neurological system process, and cell junction organization. Changes in the expression levels of transforming growth factor beta 1 (TGF-β1), caspase-8, and heat shock protein 90 alpha (HSP90α) were also verified by western blot analysis. To our knowledge, this study is the first time the response profile of ST host cells following TGEV infection has been analyzed using iTRAQ technology, and our description of the late proteomic changes that are occurring after the time of vigorous viral production are novel. Therefore, this study provides a solid foundation for further investigation, and will likely help us to better understand the mechanisms of TGEV infection and pathogenesis.",2014 Oct 21,"['Ma, Ruili', 'Zhang, Yanming', 'Liu, Haiquan', 'Ning, Pengbo']",PLoS One,,,True
ba2f1457928b26ae7f4ad64983bac74a4e383378,PMC,Identification of Antigenic Proteins of the Nosocomial Pathogen Klebsiella pneumoniae,http://dx.doi.org/10.1371/journal.pone.0110703,PMC4205017,25333280,CC BY,"The continuous expansion of nosocomial infections around the globe has become a precarious situation. Key challenges include mounting dissemination of multiple resistances to antibiotics, the easy transmission and the growing mortality rates of hospital-acquired bacterial diseases. Thus, new ways to rapidly detect these infections are vital. Consequently, researchers around the globe pursue innovative approaches for point-of-care devices. In many cases the specific interaction of an antigen and a corresponding antibody is pivotal. However, the knowledge about suitable antigens is lacking. The aim of this study was to identify novel antigens as specific diagnostic markers. Additionally, these proteins might be aptly used for the generation of vaccines to improve current treatment options. Hence, a cDNA-based expression library was constructed and screened via microarrays to detect novel antigens of Klebsiella pneumoniae, a prominent agent of nosocomial infections well-known for its extensive antibiotics resistance, especially by extended-spectrum beta-lactamases (ESBL). After screening 1536 clones, 14 previously unknown immunogenic proteins were identified. Subsequently, each protein was expressed in full-length and its immunodominant character examined by ELISA and microarray analyses. Consequently, six proteins were selected for epitope mapping and three thereof possessed linear epitopes. After specificity analysis, homology survey and 3d structural modelling, one epitope sequence GAVVALSTTFA of KPN_00363, an ion channel protein, was identified harboring specificity for K. pneumoniae. The remaining epitopes showed ambiguous results regarding the specificity for K. pneumoniae. The approach adopted herein has been successfully utilized to discover novel antigens of Campylobacter jejuni and Salmonella enterica antigens before. Now, we have transferred this knowledge to the key nosocomial agent, K. pneumoniae. By identifying several novel antigens and their linear epitope sites, we have paved the way for crucial future research and applications including the design of point-of-care devices, vaccine development and serological screenings for a highly relevant nosocomial pathogen.",2014 Oct 21,"['Hoppe, Sebastian', 'Bier, Frank F.', 'von Nickisch-Rosenegk, Markus']",PLoS One,,,True
bdedfae3a14b3da115a9fd9d38823cd0a547eee6,PMC,Identification of Antigenic Proteins of the Nosocomial Pathogen Klebsiella pneumoniae,http://dx.doi.org/10.1371/journal.pone.0110703,PMC4205017,25333280,CC BY,"The continuous expansion of nosocomial infections around the globe has become a precarious situation. Key challenges include mounting dissemination of multiple resistances to antibiotics, the easy transmission and the growing mortality rates of hospital-acquired bacterial diseases. Thus, new ways to rapidly detect these infections are vital. Consequently, researchers around the globe pursue innovative approaches for point-of-care devices. In many cases the specific interaction of an antigen and a corresponding antibody is pivotal. However, the knowledge about suitable antigens is lacking. The aim of this study was to identify novel antigens as specific diagnostic markers. Additionally, these proteins might be aptly used for the generation of vaccines to improve current treatment options. Hence, a cDNA-based expression library was constructed and screened via microarrays to detect novel antigens of Klebsiella pneumoniae, a prominent agent of nosocomial infections well-known for its extensive antibiotics resistance, especially by extended-spectrum beta-lactamases (ESBL). After screening 1536 clones, 14 previously unknown immunogenic proteins were identified. Subsequently, each protein was expressed in full-length and its immunodominant character examined by ELISA and microarray analyses. Consequently, six proteins were selected for epitope mapping and three thereof possessed linear epitopes. After specificity analysis, homology survey and 3d structural modelling, one epitope sequence GAVVALSTTFA of KPN_00363, an ion channel protein, was identified harboring specificity for K. pneumoniae. The remaining epitopes showed ambiguous results regarding the specificity for K. pneumoniae. The approach adopted herein has been successfully utilized to discover novel antigens of Campylobacter jejuni and Salmonella enterica antigens before. Now, we have transferred this knowledge to the key nosocomial agent, K. pneumoniae. By identifying several novel antigens and their linear epitope sites, we have paved the way for crucial future research and applications including the design of point-of-care devices, vaccine development and serological screenings for a highly relevant nosocomial pathogen.",2014 Oct 21,"['Hoppe, Sebastian', 'Bier, Frank F.', 'von Nickisch-Rosenegk, Markus']",PLoS One,,,False
2a2a3087f3f753cbfdab460a0a31c0ac64b0cc52,PMC,Not all cows are epidemiologically equal: quantifying the risks of bovine viral diarrhoea virus (BVDV) transmission through cattle movements,http://dx.doi.org/10.1186/s13567-014-0110-y,PMC4206702,25323831,CC BY,"Many economically important cattle diseases spread between herds through livestock movements. Traditionally, most transmission models have assumed that all purchased cattle carry the same risk of generating outbreaks in the destination herd. Using data on bovine viral diarrhoea virus (BVDV) in Scotland as a case example, this study provides empirical and theoretical evidence that the risk of disease transmission varies substantially based on the animal and herd demographic characteristics at the time of purchase. Multivariable logistic regression analysis revealed that purchasing pregnant heifers and open cows sold with a calf at foot were associated with an increased risk of beef herds being seropositive for BVDV. Based on the results from a dynamic within-herd simulation model, these findings may be partly explained by the age-related probability of animals being persistently infected with BVDV as well as the herd demographic structure at the time of animal introductions. There was also evidence that an epidemiologically important network statistic, “betweenness centrality” (a measure frequently associated with the potential for herds to acquire and transmit disease), was significantly higher for herds that supplied these particular types of replacement beef cattle. The trends for dairy herds were not as clear, although there was some evidence that open heifers and open lactating cows were associated with an increased risk of BVDV. Overall, these findings have important implications for developing simulation models that more accurately reflect the industry-level transmission dynamics of infectious cattle diseases.",2014 Oct 17,"['Gates, M Carolyn', 'Humphry, Roger W', 'Gunn, George J', 'Woolhouse, Mark E J']",Vet Res,,,True
63e680dd648bb477a87f55d53d3f0ff3f2c18e0a,PMC,Transmission dynamics and control of Ebola virus disease (EVD): a review,http://dx.doi.org/10.1186/s12916-014-0196-0,PMC4207625,25300956,CC BY,"The complex and unprecedented Ebola epidemic ongoing in West Africa has highlighted the need to review the epidemiological characteristics of Ebola Virus Disease (EVD) as well as our current understanding of the transmission dynamics and the effect of control interventions against Ebola transmission. Here we review key epidemiological data from past Ebola outbreaks and carry out a comparative review of mathematical models of the spread and control of Ebola in the context of past outbreaks and the ongoing epidemic in West Africa. We show that mathematical modeling offers useful insights into the risk of a major epidemic of EVD and the assessment of the impact of basic public health measures on disease spread. We also discuss the critical need to collect detailed epidemiological data in real-time during the course of an ongoing epidemic, carry out further studies to estimate the effectiveness of interventions during past outbreaks and the ongoing epidemic, and develop large-scale modeling studies to study the spread and control of viral hemorrhagic fevers in the context of the highly heterogeneous economic reality of African countries.",2014 Oct 10,"['Chowell, Gerardo', 'Nishiura, Hiroshi']",BMC Med,,,True
2b7d5e5ebeba8a9731ed1e98a3ee177499fed7db,PMC,Hepatitis C Virus Infection as a Traumatic Experience,http://dx.doi.org/10.1371/journal.pone.0110529,PMC4207714,25340574,CC BY,"OBJECTIVE: The purpose of this study was to evaluate whether individuals consider their HCV infection to be a potentially traumatic experience. Additionally, we investigated its association with Post-Traumatic Stress Disorder (PTSD) and the impact of PTSD diagnosis on health-related quality of life (HRQoL) in HCV infected subjects. METHODS: We conducted a cross-sectional survey of 127 HCV-infected outpatients recruited at a University Hospital in Salvador, Brazil. All subjects answered an orally-administered questionnaire to gather clinical and socio-demographic data. We investigated traumatic experiences and the subject's perception of the disease using the Trauma History Questionnaire. PTSD and other psychiatric diagnoses were assessed through the Mini International Neuropsychiatric Interview-Brazilian Version 5.0.0 (M.I.N.I. PLUS). HRQoL was assessed using Short-Form 36 (SF-36). RESULTS: Approximately 38.6% of the patients considered hepatitis C to be a traumatic experience. Of these, 60.7% had a PTSD diagnosis. PTSD was associated with significant impairment in quality of life for individuals in seven SF-36 domains as shown bymultivariate analysis: Role-Physical (β: −24.85; 95% CI: −42.08; −7.61), Bodily Pain (β: −19.36; 95% CI: −31.28; −7.45), General Health (β: −20.79; 95% CI: −29.65; −11.92), Vitality (β: −11.92; 95% CI: −20.74; −3.1), Social Functioning (β: −34.73; 95% CI: −46.79; −22.68), Role-Emotional (β: −26.07; 95% CI: −44.61; −7.53), Mental Health (β: −17.46; 95% CI: −24.38; −10.54). CONCLUSION: HCV is frequently a traumatic experience and it is strongly associated with PTSD diagnosis. PTSD significantly impaired HRQoL.",2014 Oct 23,"['Morais-de-Jesus, Mychelle', 'Daltro-Oliveira, Renato', 'Pettersen, Karine Miranda', 'Dantas-Duarte, Adriana', 'Amaral, Luciana Di-Domizio', 'Cavalcanti-Ribeiro, Patrícia', 'Santos, Carlos Teles', 'Schinoni, Maria Isabel', 'Netto, Liana R.', 'Araújo-de-Freitas, Lucas', 'Paraná, Raymundo', 'Miranda-Scippa, Ângela', 'Koenen, Karestan C.', 'Quarantini, Lucas C.']",PLoS One,,,True
bb6be6d67dbc92ee528f4c09ca1643eeda4316bd,PMC,Epidemiological and Virological Characteristics of Influenza Viruses Circulating in Cambodia from 2009 to 2011,http://dx.doi.org/10.1371/journal.pone.0110713,PMC4207757,25340711,CC0,"BACKGROUND: The Cambodian National Influenza Center (NIC) monitored and characterized circulating influenza strains from 2009 to 2011. METHODOLOGY/PRINCIPAL FINDINGS: Sentinel and study sites collected nasopharyngeal specimens for diagnostic detection, virus isolation, antigenic characterization, sequencing and antiviral susceptibility analysis from patients who fulfilled case definitions for influenza-like illness, acute lower respiratory infections and event-based surveillance. Each year in Cambodia, influenza viruses were detected mainly from June to November, during the rainy season. Antigenic analysis show that A/H1N1pdm09 isolates belonged to the A/California/7/2009-like group. Circulating A/H3N2 strains were A/Brisbane/10/2007-like in 2009 before drifting to A/Perth/16/2009-like in 2010 and 2011. The Cambodian influenza B isolates from 2009 to 2011 all belonged to the B/Victoria lineage represented by the vaccine strains B/Brisbane/60/2008 and B/Malaysia/2506/2004. Sequences of the M2 gene obtained from representative 2009–2011 A/H3N2 and A/H1N1pdm09 strains all contained the S31N mutation associated with adamantanes resistance except for one A/H1N1pdm09 strain isolated in 2011 that lacked this mutation. No reduction in the susceptibility to neuraminidase inhibitors was observed among the influenza viruses circulating from 2009 to 2011. Phylogenetic analysis revealed that A/H3N2 strains clustered each year to a distinct group while most A/H1N1pdm09 isolates belonged to the S203T clade. CONCLUSIONS/SIGNIFICANCE: In Cambodia, from 2009 to 2011, influenza activity occurred throughout the year with peak seasonality during the rainy season from June to November. Seasonal influenza epidemics were due to multiple genetically distinct viruses, even though all of the isolates were antigenically similar to the reference vaccine strains. The drug susceptibility profile of Cambodian influenza strains revealed that neuraminidase inhibitors would be the drug of choice for influenza treatment and chemoprophylaxis in Cambodia, as adamantanes are no longer expected to be effective.",2014 Oct 23,"['Horm, Srey Viseth', 'Mardy, Sek', 'Rith, Sareth', 'Ly, Sovann', 'Heng, Seng', 'Vong, Sirenda', 'Kitsutani, Paul', 'Ieng, Vannra', 'Tarantola, Arnaud', 'Ly, Sowath', 'Sar, Borann', 'Chea, Nora', 'Sokhal, Buth', 'Barr, Ian', 'Kelso, Anne', 'Horwood, Paul F.', 'Timmermans, Ans', 'Hurt, Aeron', 'Lon, Chanthap', 'Saunders, David', 'Ung, Sam An', 'Asgari, Nima', 'Roces, Maria Concepcion', 'Touch, Sok', 'Komadina, Naomi', 'Buchy, Philippe']",PLoS One,,,True
e50473adb66bac4a176d80051d63f415d2dbd5a8,PMC,Integrin β3 Is Required in Infection and Proliferation of Classical Swine Fever Virus,http://dx.doi.org/10.1371/journal.pone.0110911,PMC4207786,25340775,CC BY,"Classical Swine Fever (CSF) is a highly infectious fatal pig disease, resulting in huge economic loss to the swine industry. Integrins are membrane-bound signal mediators, expressed on a variety of cell surfaces and are known as receptors or co-receptors for many viruses. However, the role of integrin β3 in CSFV infection is unknown. Here, through quantitive PCR, immunofluorescence (IFC) and immunocytohistochemistry (ICC), we revealed that ST (swine testicles epithelial) cells have a prominent advantage in CSFV proliferation as compared to EC (swine umbilical vein endothelial cell), IEC (swine intestinal epithelial cell) and PK (porcine kidney epithelial) cells. Meanwhile, ST cells had remarkably more integrin β3 expression as compared to EC, IEC and PK cells, which was positively correlated with CSFV infection and proliferation. Integrin β3 was up-regulated post CSFV infection in all the four cell lines, while the CSFV proliferation rate was decreased in integrin β3 function-blocked cells. ShRNA1755 dramatically decreased integrin β3, with a deficiency of 96% at the mRNA level and 80% at the protein level. CSFV proliferation was dramatically reduced in integrin β3 constantly-defected cells (ICDC), with the deficiencies of 92.6%, 99% and 81.7% at 24 h, 48 h and 72 h post CSFV infection, respectively. These results demonstrate that integrin β3 is required in CSFV infection and proliferation, which provide a new insight into the mechanism of CSFV infection.",2014 Oct 23,"['Li, Weiwei', 'Wang, Gang', 'Liang, Wulong', 'Kang, Kai', 'Guo, Kangkang', 'Zhang, Yanming']",PLoS One,,,True
63cbd57061c1709dc5aca57716a3ab95f6ba6446,PMC,Growth Patterns and Scaling Laws Governing AIDS Epidemic in Brazilian Cities,http://dx.doi.org/10.1371/journal.pone.0111015,PMC4207789,25340796,CC BY,"Brazil holds approximately 1/3 of population living infected with AIDS (acquired immunodeficiency syndrome) in Central and South Americas, and it was also the first developing country to implement a large-scale control and intervention program against AIDS epidemic. In this scenario, we investigate the temporal evolution and current status of the AIDS epidemic in Brazil. Specifically, we analyze records of annual absolute frequency of cases for more than 5000 cities for the first 33 years of the infection in Brazil. We found that (i) the annual absolute frequencies exhibit a logistic-type growth with an exponential regime in the first few years of the AIDS spreading; (ii) the actual reproduction number decaying as a power law; (iii) the distribution of the annual absolute frequencies among cities decays with a power law behavior; (iv) the annual absolute frequencies and the number of inhabitants have an allometric relationship; (v) the temporal evolution of the annual absolute frequencies have different profile depending on the average annual absolute frequencies in the cities. These findings yield a general quantitative description of the AIDS infection dynamics in Brazil since the beginning. They also provide clues about the effectiveness of treatment and control programs against the infection, that has had a different impact depending on the number of inhabitants of cities. In this framework, our results give insights into the overall dynamics of AIDS epidemic, which may contribute to select empirically accurate models.",2014 Oct 23,"['Antonio, Fernando Jose', 'de Picoli, Sergio', 'Teixeira, Jorge Juarez Vieira', 'Mendes, Renio dos Santos']",PLoS One,,,True
64053a0785373722d802b6a2fac9db7489b1474e,PMC,"Contact Heterogeneity, Rather Than Transmission Efficiency, Limits the Emergence and Spread of Canine Influenza Virus",http://dx.doi.org/10.1371/journal.ppat.1004455,PMC4207809,25340642,CC BY,"Host-range shifts in influenza virus are a major risk factor for pandemics. A key question in the study of emerging zoonoses is how the evolution of transmission efficiency interacts with heterogeneity in contact patterns in the new host species, as this interplay influences disease dynamics and prospects for control. Here we use a synergistic mixture of models and data to tease apart the evolutionary and demographic processes controlling a host-range shift in equine H3N8-derived canine influenza virus (CIV). CIV has experienced 15 years of continuous transfer among dogs in the United States, but maintains a patchy distribution, characterized by sporadic short-lived outbreaks coupled with endemic hotspots in large animal shelters. We show that CIV has a high reproductive potential in these facilities (mean R(0) = 3.9) and that these hotspots act as refugia from the sparsely connected majority of the dog population. Intriguingly, CIV has evolved a transmission efficiency that closely matches the minimum required to persist in these refugia, leaving it poised on the extinction/invasion threshold of the host contact network. Corresponding phylogenetic analyses show strong geographic clustering in three US regions, and that the effective reproductive number of the virus (R(e)) in the general dog population is close to 1.0. Our results highlight the critical role of host contact structure in CIV dynamics, and show how host contact networks could shape the evolution of pathogen transmission efficiency. Importantly, efficient control measures could eradicate the virus, in turn minimizing the risk of future sustained transmission among companion dogs that could represent a potential new axis to the human-animal interface for influenza.",2014 Oct 23,"['Dalziel, Benjamin D.', 'Huang, Kai', 'Geoghegan, Jemma L.', 'Arinaminpathy, Nimalan', 'Dubovi, Edward J.', 'Grenfell, Bryan T.', 'Ellner, Stephen P.', 'Holmes, Edward C.', 'Parrish, Colin R.']",PLoS Pathog,,,True
4c6112b657933e7254342266bc7afdeb42af507d,PMC,"Contact Heterogeneity, Rather Than Transmission Efficiency, Limits the Emergence and Spread of Canine Influenza Virus",http://dx.doi.org/10.1371/journal.ppat.1004455,PMC4207809,25340642,CC BY,"Host-range shifts in influenza virus are a major risk factor for pandemics. A key question in the study of emerging zoonoses is how the evolution of transmission efficiency interacts with heterogeneity in contact patterns in the new host species, as this interplay influences disease dynamics and prospects for control. Here we use a synergistic mixture of models and data to tease apart the evolutionary and demographic processes controlling a host-range shift in equine H3N8-derived canine influenza virus (CIV). CIV has experienced 15 years of continuous transfer among dogs in the United States, but maintains a patchy distribution, characterized by sporadic short-lived outbreaks coupled with endemic hotspots in large animal shelters. We show that CIV has a high reproductive potential in these facilities (mean R(0) = 3.9) and that these hotspots act as refugia from the sparsely connected majority of the dog population. Intriguingly, CIV has evolved a transmission efficiency that closely matches the minimum required to persist in these refugia, leaving it poised on the extinction/invasion threshold of the host contact network. Corresponding phylogenetic analyses show strong geographic clustering in three US regions, and that the effective reproductive number of the virus (R(e)) in the general dog population is close to 1.0. Our results highlight the critical role of host contact structure in CIV dynamics, and show how host contact networks could shape the evolution of pathogen transmission efficiency. Importantly, efficient control measures could eradicate the virus, in turn minimizing the risk of future sustained transmission among companion dogs that could represent a potential new axis to the human-animal interface for influenza.",2014 Oct 23,"['Dalziel, Benjamin D.', 'Huang, Kai', 'Geoghegan, Jemma L.', 'Arinaminpathy, Nimalan', 'Dubovi, Edward J.', 'Grenfell, Bryan T.', 'Ellner, Stephen P.', 'Holmes, Edward C.', 'Parrish, Colin R.']",PLoS Pathog,,,False
36c1c6bc314487fe898f76a7093175d90347ac20,PMC,Genetic polymorphisms and risk of recurrent wheezing in pediatric age,http://dx.doi.org/10.1186/1471-2466-14-162,PMC4210469,25326706,CC BY,"BACKGROUND: Wheezing during early life is a very common disorder, but the reasons underlying the different wheezing phenotypes are still unclear. The aims of this study were to analyse the potential correlations between the risk of developing recurrent wheezing and the presence of specific polymorphisms of some genes regulating immune system function, and to study the relative importance of the associations of different viruses and genetic polymorphisms in causing recurrent episodes. METHODS: The study involved 119 otherwise healthy infants admitted to hospital for a first episode of wheezing (74 of whom subsequently experienced recurrent episodes) and 119 age- and sex-matched subjects without any history of respiratory problem randomly selected from those attending our outpatient clinic during the study period. All of the study subjects were followed up for two years, and 47 single nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped on whole blood using an ABI PRISM 7900 HT Fast Real-time instrument. RESULTS: IL8-rs4073AT, VEGFA-rs833058CT, MBL2-rs1800450CT and IKBKB-rs3747811AT were associated with a significantly increased risk of developing wheezing (p = 0.02, p = 0.03, p = 0.05 and p = 0.0018), whereas CTLA4-rs3087243AG and NFKBIB-rs3136641TT were associated with a significantly reduced risk (p = 0.05 and p = 0.04). IL8-rs4073AT, VEGFA-rs2146323AA and NFKBIA-rs2233419AG were associated with a significantly increased risk of developing recurrent wheezing (p = 0.04, p = 0.04 and p = 0.03), whereas TLR3-rs3775291TC was associated with a significantly reduced risk (p = 0.03). Interestingly, the study of gene-environment interactions showed that rhinovirus was significantly associated with recurrent wheezing in the presence of IL4Ra-rs1801275GG and G (odds ratio [OR] 6.03, 95% confidence interval [CI]: 1.21-30.10, p = 0.03) and MAP3K1-rs702689AA (OR 4.09, 95% CI: 1.14-14.61, p = 0.03). CONCLUSIONS: This study shows a clear relationship between the risk of wheezing and polymorphisms of some genes involved in the immune response. Although further studies are needed to confirm the results, these findings may be useful for the early identification of children at the highest risk of developing recurrent episodes and possibly subsequent asthma.",2014 Oct 18,"['Esposito, Susanna', 'Ierardi, Valentina', 'Daleno, Cristina', 'Scala, Alessia', 'Terranova, Leonardo', 'Tagliabue, Claudia', 'Rios, Walter Peves', 'Pelucchi, Claudio', 'Principi, Nicola']",BMC Pulm Med,,,True
5bae3e47050469780ae94d2f254ab80221178ebf,PMC,Autoimmune and Neoplastic Thyroid Diseases Associated with Hepatitis C Chronic Infection,http://dx.doi.org/10.1155/2014/935131,PMC4211174,25374602,CC BY,"Frequently, patients with hepatitis C virus (HCV) chronic infection have high levels of serum anti-thyroperoxidase and/or anti-thyroglobulin autoantibodies, ultrasonographic signs of chronic autoimmune thyroiditis, and subclinical hypothyroidism, in female gender versus healthy controls, or hepatitis B virus infected patients. In patients with “HCV-associated mixed cryoglobulinemia” (MC + HCV), a higher prevalence of thyroid autoimmune disorders was shown not only compared to controls, but also versus HCV patients without cryoglobulinemia. Patients with MC + HCV or HCV chronic infection show a higher prevalence of papillary thyroid cancer than controls, in particular in patients with autoimmune thyroiditis. Patients with HCV chronic infection, or with MC + HCV, in presence of autoimmune thyroiditis, show higher serum levels of T-helper (Th)1 (C-X-C motif) ligand 10 (CXCL10) chemokine, but normal levels of Th2 (C-C motif) ligand 2 chemokine, than patients without thyroiditis. HCV thyroid infection could act by upregulating CXCL10 gene expression and secretion in thyrocytes recruiting Th1 lymphocytes that secrete interferon-γ and tumor necrosis factor-α. These cytokines might induce a further CXCL10 secretion by thyrocytes, thus perpetuating the immune cascade, which may lead to the appearance of autoimmune thyroid disorders in genetically predisposed subjects. A careful monitoring of thyroid function, particularly where nodules occur, is recommended in HCV patients.",2014 Oct 13,"['Fallahi, Poupak', 'Ferrari, Silvia Martina', 'Politti, Ugo', 'Giuggioli, Dilia', 'Ferri, Clodoveo', 'Antonelli, Alessandro']",Int J Endocrinol,,,True
60a7721ab454f05f6622087ecde3b186b505779f,PMC,Isolation Facilities for Highly Infectious Diseases in Europe – A Cross-Sectional Analysis in 16 Countries,http://dx.doi.org/10.1371/journal.pone.0100401,PMC4211666,25350843,CC BY,"BACKGROUND: Highly Infectious Diseases (HIDs) are (i) easily transmissible form person to person; (ii) cause a life-threatening illness with no or few treatment options; and (iii) pose a threat for both personnel and the public. Hence, even suspected HID cases should be managed in specialised facilities minimizing infection risks but allowing state-of-the-art critical care. Consensus statements on the operational management of isolation facilities have been published recently. The study presented was set up to compare the operational management, resources, and technical equipment among European isolation facilities. Due to differences in geography, population density, and national response plans it was hypothesized that adherence to recommendations will vary. METHODS AND FINDINGS: Until mid of 2010 the European Network for Highly Infectious Diseases conducted a cross-sectional analysis of isolation facilities in Europe, recruiting 48 isolation facilities in 16 countries. Three checklists were disseminated, assessing 44 items and 148 specific questions. The median feedback rate for specific questions was 97.9% (n = 47/48) (range: n = 7/48 (14.6%) to n = 48/48 (100%). Although all facilities enrolled were nominated specialised facilities' serving countries or regions, their design, equipment and personnel management varied. Eighteen facilities fulfilled the definition of a High Level Isolation Unit'. In contrast, 24 facilities could not operate independently from their co-located hospital, and five could not ensure access to equipment essential for infection control. Data presented are not representative for the EU in general, as only 16/27 (59.3%) of all Member States agreed to participate. Another limitation of this study is the time elapsed between data collection and publication; e.g. in Germany one additional facility opened in the meantime. CONCLUSION: There are disparities both within and between European countries regarding the design and equipment of isolation facilities. With regard to the International Health Regulations, terminology, capacities and equipment should be standardised.",2014 Oct 28,"['Schilling, Stefan', 'Fusco, Francesco Maria', 'De Iaco, Giuseppina', 'Bannister, Barbara', 'Maltezou, Helena C.', 'Carson, Gail', 'Gottschalk, Rene', 'Brodt, Hans-Reinhard', 'Brouqui, Philippe', 'Puro, Vincenzo', 'Ippolito, Giuseppe', None]",PLoS One,,,True
9b2ee0cdb3b92a377acec0e84a63090005b6b7ed,PMC,Identification of Protein Interaction Partners in Mammalian Cells Using SILAC-immunoprecipitation Quantitative Proteomics,http://dx.doi.org/10.3791/51656,PMC4212580,25046639,CC BY,"Quantitative proteomics combined with immuno-affinity purification, SILAC immunoprecipitation, represent a powerful means for the discovery of novel protein:protein interactions. By allowing the accurate relative quantification of protein abundance in both control and test samples, true interactions may be easily distinguished from experimental contaminants. Low affinity interactions can be preserved through the use of less-stringent buffer conditions and remain readily identifiable. This protocol discusses the labeling of tissue culture cells with stable isotope labeled amino acids, transfection and immunoprecipitation of an affinity tagged protein of interest, followed by the preparation for submission to a mass spectrometry facility. This protocol then discusses how to analyze and interpret the data returned from the mass spectrometer in order to identify cellular partners interacting with a protein of interest. As an example this technique is applied to identify proteins binding to the eukaryotic translation initiation factors: eIF4AI and eIF4AII.",2014 Jul 6,"['Emmott, Edward', 'Goodfellow, Ian']",J Vis Exp,,,True
a3156b64bff879eba0b2b9a0e81adc1c5dead42c,PMC,Harnessing Mechanistic Knowledge on Beneficial Versus Deleterious IFN-I Effects to Design Innovative Immunotherapies Targeting Cytokine Activity to Specific Cell Types,http://dx.doi.org/10.3389/fimmu.2014.00526,PMC4214202,25400632,CC BY,"Type I interferons (IFN-I) were identified over 50 years ago as cytokines critical for host defense against viral infections. IFN-I promote anti-viral defense through two main mechanisms. First, IFN-I directly reinforce or induce de novo in potentially all cells the expression of effector molecules of intrinsic anti-viral immunity. Second, IFN-I orchestrate innate and adaptive anti-viral immunity. However, IFN-I responses can be deleterious for the host in a number of circumstances, including secondary bacterial or fungal infections, several autoimmune diseases, and, paradoxically, certain chronic viral infections. We will review the proposed nature of protective versus deleterious IFN-I responses in selected diseases. Emphasis will be put on the potentially deleterious functions of IFN-I in human immunodeficiency virus type 1 (HIV-1) infection, and on the respective roles of IFN-I and IFN-III in promoting resolution of hepatitis C virus (HCV) infection. We will then discuss how the balance between beneficial versus deleterious IFN-I responses is modulated by several key parameters including (i) the subtypes and dose of IFN-I produced, (ii) the cell types affected by IFN-I, and (iii) the source and timing of IFN-I production. Finally, we will speculate how integration of this knowledge combined with advanced biochemical manipulation of the activity of the cytokines should allow designing innovative immunotherapeutic treatments in patients. Specifically, we will discuss how induction or blockade of specific IFN-I responses in targeted cell types could promote the beneficial functions of IFN-I and/or dampen their deleterious effects, in a manner adapted to each disease.",2014 Oct 30,"['Tomasello, Elena', 'Pollet, Emeline', 'Vu Manh, Thien-Phong', 'Uzé, Gilles', 'Dalod, Marc']",Front Immunol,,,True
28f13f534ff3d7fccd966a9bb1158a0a1ed95967,PMC,Spatial Analysis on Hepatitis C Virus Infection in Mainland China: From 2005 to 2011,http://dx.doi.org/10.1371/journal.pone.0110861,PMC4214689,25356554,CC BY,"BACKGROUND: The burden of Hepatitis C virus (HCV) has become more and more considerable in China. A macroscopic spatial analysis of HCV infection that can provide scientific information for further intervention and disease control is lacking. METHODS: All geo-referenced HCV cases that had been recorded by the China Information System for Disease Control and Prevention (CISDCP) during 2005–2011 were included in the study. In order to learn about the changes of demographic characteristics and geographic distribution, trend test and spatial analysis were conducted to reflect the changing pattern of HCV infection. RESULTS: Over 770,000 identified HCV infection cases had specific geographic information during the study period (2005–2011). Ratios of gender (Male/Female, Z-value  = −18.53, P<0.001), age group (≤30 years old/≥31 years old, Z-value  = −51.03, P<0.001) and diagnosis type (Clinical diagnosis/Laboratory diagnosis, Z-value  = −130.47, P<0.001) declined. HCV infection was not distributed randomly. Provinces Henan, Guangdong, Guangxi, Xinjiang, and Jilin reported more than 40,000 HCV infections during 2005 to 2011, accounting for 43.91% of all cases. The strength of cluster of disease was increasing in China during the study period. Overall, 11 provinces had once been detected as hotspots during 7 years, most of which were located in the central or border parts of China. Tibet, Qinghai, Jiangxi were the regions that had coldspots. CONCLUSIONS: The number of clustering of HCV infection among older adults increased in recent years. Specific interventions and prevention programs targeting at main HCV epidemic areas are urgently in need in mainland China.",2014 Oct 30,"['Wang, Lu', 'Xing, Jiannan', 'Chen, Fangfang', 'Yan, Ruixue', 'Ge, Lin', 'Qin, Qianqian', 'Wang, Liyan', 'Ding, Zhengwei', 'Guo, Wei', 'Wang, Ning']",PLoS One,,,True
a034fc1a3e926d0e12339678c32e892c37f514cb,PMC,Detecting Differential Transmissibilities That Affect the Size of Self-Limited Outbreaks,http://dx.doi.org/10.1371/journal.ppat.1004452,PMC4214794,25356657,CC0,"Our ability to respond appropriately to infectious diseases is enhanced by identifying differences in the potential for transmitting infection between individuals. Here, we identify epidemiological traits of self-limited infections (i.e. infections with an effective reproduction number satisfying [Image: see text]) that correlate with transmissibility. Our analysis is based on a branching process model that permits statistical comparison of both the strength and heterogeneity of transmission for two distinct types of cases. Our approach provides insight into a variety of scenarios, including the transmission of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the Arabian peninsula, measles in North America, pre-eradication smallpox in Europe, and human monkeypox in the Democratic Republic of the Congo. When applied to chain size data for MERS-CoV transmission before 2014, our method indicates that despite an apparent trend towards improved control, there is not enough statistical evidence to indicate that [Image: see text] has declined with time. Meanwhile, chain size data for measles in the United States and Canada reveal statistically significant geographic variation in [Image: see text], suggesting that the timing and coverage of national vaccination programs, as well as contact tracing procedures, may shape the size distribution of observed infection clusters. Infection source data for smallpox suggests that primary cases transmitted more than secondary cases, and provides a quantitative assessment of the effectiveness of control interventions. Human monkeypox, on the other hand, does not show evidence of differential transmission between animals in contact with humans, primary cases, or secondary cases, which assuages the concern that social mixing can amplify transmission by secondary cases. Lastly, we evaluate surveillance requirements for detecting a change in the human-to-human transmission of monkeypox since the cessation of cross-protective smallpox vaccination. Our studies lay the foundation for future investigations regarding how infection source, vaccination status or other putative transmissibility traits may affect self-limited transmission.",2014 Oct 30,"['Blumberg, Seth', 'Funk, Sebastian', 'Pulliam, Juliet R. C.']",PLoS Pathog,,,True
917fc85b2bd24410181d77246ad89c49e5d6f7b0,PMC,Detecting Differential Transmissibilities That Affect the Size of Self-Limited Outbreaks,http://dx.doi.org/10.1371/journal.ppat.1004452,PMC4214794,25356657,CC0,"Our ability to respond appropriately to infectious diseases is enhanced by identifying differences in the potential for transmitting infection between individuals. Here, we identify epidemiological traits of self-limited infections (i.e. infections with an effective reproduction number satisfying [Image: see text]) that correlate with transmissibility. Our analysis is based on a branching process model that permits statistical comparison of both the strength and heterogeneity of transmission for two distinct types of cases. Our approach provides insight into a variety of scenarios, including the transmission of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the Arabian peninsula, measles in North America, pre-eradication smallpox in Europe, and human monkeypox in the Democratic Republic of the Congo. When applied to chain size data for MERS-CoV transmission before 2014, our method indicates that despite an apparent trend towards improved control, there is not enough statistical evidence to indicate that [Image: see text] has declined with time. Meanwhile, chain size data for measles in the United States and Canada reveal statistically significant geographic variation in [Image: see text], suggesting that the timing and coverage of national vaccination programs, as well as contact tracing procedures, may shape the size distribution of observed infection clusters. Infection source data for smallpox suggests that primary cases transmitted more than secondary cases, and provides a quantitative assessment of the effectiveness of control interventions. Human monkeypox, on the other hand, does not show evidence of differential transmission between animals in contact with humans, primary cases, or secondary cases, which assuages the concern that social mixing can amplify transmission by secondary cases. Lastly, we evaluate surveillance requirements for detecting a change in the human-to-human transmission of monkeypox since the cessation of cross-protective smallpox vaccination. Our studies lay the foundation for future investigations regarding how infection source, vaccination status or other putative transmissibility traits may affect self-limited transmission.",2014 Oct 30,"['Blumberg, Seth', 'Funk, Sebastian', 'Pulliam, Juliet R. C.']",PLoS Pathog,,,True
7e79ee45307f38f4d8935a6ac728ee4d089a0d53,PMC,Detecting Differential Transmissibilities That Affect the Size of Self-Limited Outbreaks,http://dx.doi.org/10.1371/journal.ppat.1004452,PMC4214794,25356657,CC0,"Our ability to respond appropriately to infectious diseases is enhanced by identifying differences in the potential for transmitting infection between individuals. Here, we identify epidemiological traits of self-limited infections (i.e. infections with an effective reproduction number satisfying [Image: see text]) that correlate with transmissibility. Our analysis is based on a branching process model that permits statistical comparison of both the strength and heterogeneity of transmission for two distinct types of cases. Our approach provides insight into a variety of scenarios, including the transmission of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the Arabian peninsula, measles in North America, pre-eradication smallpox in Europe, and human monkeypox in the Democratic Republic of the Congo. When applied to chain size data for MERS-CoV transmission before 2014, our method indicates that despite an apparent trend towards improved control, there is not enough statistical evidence to indicate that [Image: see text] has declined with time. Meanwhile, chain size data for measles in the United States and Canada reveal statistically significant geographic variation in [Image: see text], suggesting that the timing and coverage of national vaccination programs, as well as contact tracing procedures, may shape the size distribution of observed infection clusters. Infection source data for smallpox suggests that primary cases transmitted more than secondary cases, and provides a quantitative assessment of the effectiveness of control interventions. Human monkeypox, on the other hand, does not show evidence of differential transmission between animals in contact with humans, primary cases, or secondary cases, which assuages the concern that social mixing can amplify transmission by secondary cases. Lastly, we evaluate surveillance requirements for detecting a change in the human-to-human transmission of monkeypox since the cessation of cross-protective smallpox vaccination. Our studies lay the foundation for future investigations regarding how infection source, vaccination status or other putative transmissibility traits may affect self-limited transmission.",2014 Oct 30,"['Blumberg, Seth', 'Funk, Sebastian', 'Pulliam, Juliet R. C.']",PLoS Pathog,,,False
ba7a60024505cd93efc22344fc0c956bad66d6e8,PMC,Mouse Hepatitis Virus Infection Upregulates Genes Involved in Innate Immune Responses,http://dx.doi.org/10.1371/journal.pone.0111351,PMC4216085,25360880,CC BY,"Neurotropic recombinant strain of Mouse Hepatitis Virus, RSA59, induces meningo-encephalitis, myelitis and demyelination following intracranial inoculation. RSA59 induced neuropathology is partially caused by activation of CNS resident microglia, as demonstrated by changes in cellular morphology and increased expression of a microglia/macrophage specific calcium ion binding factor, Iba1. Affymetrix Microarray analysis for mRNA expression data reveals expression of inflammatory mediators that are known to be released by activated microglia. Microglia-specific cell surface molecules, including CD11b, CD74, CD52 and CD68, are significantly upregulated in contrast to CD4, CD8 and CD19. Protein analysis of spinal cord extracts taken from mice 6 days post-inoculation, the time of peak inflammation, reveals robust expression of IFN-γ, IL-12 and mKC. Data suggest that activated microglia and inflammatory mediators contribute to a local CNS microenvironment that regulates viral replication and IFN-γ production during the acute phase of infection, which in turn can cause phagolysosome maturation and phagocytosis of the myelin sheath, leading to demyelination.",2014 Oct 31,"['Chatterjee, Dhriti', 'Addya, Sankar', 'Khan, Reas S.', 'Kenyon, Lawrence C.', 'Choe, Alexander', 'Cohrs, Randall J.', 'Shindler, Kenneth S.', 'Sarma, Jayasri Das']",PLoS One,,,True
f84decc775e81850bbfcbf71972377db10e4863c,PMC,Semen banking: consideration on viral contamination in the era of new emerging viral infection,,PMC4216451,25587263,CC BY,,2011 Spring,"Wiwanitkit, Viroj",Iran J Reprod Med,,,True
7ac11579d3d1602c4ebceee735a88cb465ff057b,PMC,The Effect of Aqueous Extract of Glycyrrhiza glabra on Herpes Simplex Virus  1,http://dx.doi.org/10.5812/jjm.11616,PMC4216581,25368801,CC BY,"BACKGROUND: Herpes Simplex Virus 1 (HSV-1) resistance to drugs and the side effects of drugs have drawn the attention of investigators to herbal plants. OBJECTIVES: The main aim of the current research was to investigate the effects of Glycyrrhiza glabra (liquorice root) on HSV-1. One of the objectives of the current research was to determine the efficacy and the effect of the elapsed incubation time of treating the Vero cells infected with HSV-1 by G. glabra. In addition, the effect of cells pretreatment with licorice root extract, preincubation of virus with licorice root extract, and the antiviral activity were assessed. PATIENTS AND METHODS: Vero cells were incubated after adding different concentrations of aqueous extracts of G. glabra. The cells were incubated during various time courses. Cytotoxicity assay, determining the 50% tissue culture infectious dose (TCID(50)), and incubation of HSV-1 with licorice root extract prior to viral infection were performed. RESULTS: Internal association among different experiment groups showed the significant difference in the efficacy of the extract with regard to incubation period between one and four hours, one and eight hours, four and 12 hours, and eight and 12 hours. Moreover, there was a significant difference with regard to efficacy among the pretreatment of cells with extract for two hours, incubation of virus with extract for one hour, incubation of virus with extract for two hours. CONCLUSIONS: G. glabra showed the characteristics of a novel antiviral medication; however, more in vitro experiments are needed to determine the antiherpetic activities of the G. glabra.",2014 Jul 1,"['Sabouri Ghannad, Masoud', 'Mohammadi, Avid', 'Safiallahy, Sohayla', 'Faradmal, Javad', 'Azizi, Mona', 'Ahmadvand, Zohreh']",Jundishapur J Microbiol,,,True
0926342a9cad40463ea13641523a95b165da8f8b,PMC,The quest for effective Ebola treatment: Ebola VP35 is an evidence-based target for dsRNA drugs,http://dx.doi.org/10.1038/emi.2014.77,PMC4217096,26038500,CC BY,,2014 Oct 29,"['Mitchell, William M', 'Carter, William A']",Emerg Microbes Infect,,,False
cbc100f9459ee41fa74a2ef65540097e420a461f,PMC,"Study of the effect on shelter cat intakes and euthanasia from a shelter neuter return project of 10,080 cats from March 2010 to June 2014",http://dx.doi.org/10.7717/peerj.646,PMC4217190,25374785,CC BY,"Cat impoundments were increasing at the municipal San Jose animal shelter in 2009, despite long-term successful low cost sterilization programs and attempts to lower the euthanasia rate of treatable-rehabilitatable impounds beginning in 2008. San Jose Animal Care and Services implemented a new strategy designed to control overall feral cat reproduction by altering and returning feral cats entering the shelter system, rather than euthanizing the cats. The purpose of this case study was to determine how the program affected the shelter cat intakes over time. In just over four years, 10,080 individual healthy adult feral cats, out of 11,423 impounded at the shelter during this time frame, were altered and returned to their site of capture. Included in the 11,423 cats were 862 cats impounded from one to four additional times for a total of 958 (9.5%) recaptures of the previously altered 10,080 cats. The remaining 385 healthy feral cats were euthanized at the shelter from March 2010 to June 2014. Four years into the program, researchers observed cat and kitten impounds decreased 29.1%; euthanasia decreased from over 70% of intakes in 2009, to 23% in 2014. Euthanasia in the shelter for Upper Respiratory Disease decreased 99%; dead cat pick up off the streets declined 20%. Dog impounds did not similarly decline over the four years. No other laws or program changes were implemented since the beginning of the program.",2014 Oct 30,"['Johnson, Karen L.', 'Cicirelli, Jon']",PeerJ,,,True
dc4332792ad6c643b1142cef1d344755a64b9625,PMC,Factors Influencing the Measurement of Plasma/Serum Surfactant Protein D Levels by ELISA,http://dx.doi.org/10.1371/journal.pone.0111466,PMC4218753,25365324,CC0,"BACKGROUND: Extensive variations in human surfactant protein D (SP-D) levels in circulation as measured by ELISA exist in the published literature. In order to determine the source of these variations, factors influencing the measurement by ELISA were explored. MATERIALS AND METHODS: Peripheral blood from healthy individuals was collected into various vacutainers during the same blood draw. Recombinant SP-D was diluted into different matrices and used for a standard curve. Samples were analyzed by capture ELISA using one of two distinct detection antibodies. RESULTS: The type of matrix had some effects on detection of recombinant SP-D. The type of anticoagulant used and dilution factor had very little effect, except for in plasma collected in EDTA vacutainers. The extent of variation in published values seemed to be due to the ELISA configuration employed, and, in agreement with this, we found that by switching the detection antibody, there was a 50% decrease in the extrapolated SP-D value of serum and plasma samples. Storage of samples resulted in slight changes in measured SP-D levels. CONCLUSIONS: The ELISA configuration employed to measure circulating levels of SP-D has a significant effect on the extrapolated values. In both configurations tested, the use of EDTA as a coagulant resulted in inconsistent values, and we, therefore, suggest the avoidance of this anticoagulant when assaying for SP-D by ELISA. While the demonstrated effects of several factors on measurement of SP-D may not account for all the disparities amongst the previous studies, they stress that variations in methodologies for measuring the same protein can result in very inconsistent results.",2014 Nov 3,"['Bratcher, Preston E.', 'Gaggar, Amit']",PLoS One,,,True
ac52347e640db03cb8dfaf1f0228caf47570ddaa,PMC,Patient-Based Transcriptome-Wide Analysis Identify Interferon and Ubiquination Pathways as Potential Predictors of Influenza A Disease Severity,http://dx.doi.org/10.1371/journal.pone.0111640,PMC4218794,25365328,CC BY,"BACKGROUND: The influenza A virus is an RNA virus that is responsible for seasonal epidemics worldwide with up to five million cases of severe illness and 500,000 deaths annually according to the World Health Organization estimates. The factors associated with severe diseases are not well defined, but more severe disease is more often seen among persons aged >65 years, infants, pregnant women, and individuals of any age with underlying health conditions. METHODOLOGY/PRINCIPAL FINDINGS: Using gene expression microarrays, the transcriptomic profiles of influenza-infected patients with severe (N = 11), moderate (N = 40) and mild (N = 83) symptoms were compared with the febrile patients of unknown etiology (N = 73). We found that influenza-infected patients, regardless of their clinical outcomes, had a stronger induction of antiviral and cytokine responses and a stronger attenuation of NK and T cell responses in comparison with those with unknown etiology. More importantly, we found that both interferon and ubiquitination signaling were strongly attenuated in patients with the most severe outcomes in comparison with those with moderate and mild outcomes, suggesting the protective roles of these pathways in disease pathogenesis. CONCLUSION/SIGNIFICANCES: The attenuation of interferon and ubiquitination pathways may associate with the clinical outcomes of influenza patients.",2014 Nov 3,"['Hoang, Long Truong', 'Tolfvenstam, Thomas', 'Ooi, Eng Eong', 'Khor, Chiea Chuen', 'Naim, Ahmand Nazri Mohamed', 'Ho, Eliza Xin Pei', 'Ong, Swee Hoe', 'Wertheim, Heiman F.', 'Fox, Annette', 'Van Vinh Nguyen, Chau', 'Nghiem, Ngoc My', 'Ha, Tuan Manh', 'Thi Ngoc Tran, Anh', 'Tambayah, Paul', 'Lin, Raymond', 'Sangsajja, Chariya', 'Manosuthi, Weerawat', 'Chuchottaworn, Chareon', 'Sansayunh, Piamlarp', 'Chotpitayasunondh, Tawee', 'Suntarattiwong, Piyarat', 'Chokephaibulkit, Kulkanya', 'Puthavathana, Pilaipan', 'de Jong, Menno D.', 'Farrar, Jeremy', 'van Doorn, H. Rogier', 'Hibberd, Martin Lloyd']",PLoS One,,,True
e0f36613dbfcdb38aee79337d0a011c8760acba0,PMC,"Antibodies against H10N8 avian influenza virus among animal workers in Guangdong Province before November 30, 2013, when the first human H10N8 case was recognized",http://dx.doi.org/10.1186/s12916-014-0205-3,PMC4219099,25348464,CC BY,"BACKGROUND: Considered an epicenter of pandemic influenza virus generation, southern China has recently seen an increasing number of human H7N9 infections. However, it is not the only threat. On 30 November 2013, a human H10N8 infection case was first described in China. The origin and genetic diversity of this novel virus is similar to that of H7N9 virus. As H10N8 avian influenza virus (AIV) was first identified from a duck in Guangdong Province during 2012 and there is also evidence of H10N8 infected dogs in this region, we sought to examine archived sera from animal workers to see if there was evidence of subclinical human infections before the first human H10N8 cases. METHODS: We studied archived serum samples (cross-sectional study, convenience sample) collected between May and September 2013 from 710 animal workers and 107 non-animal exposed volunteers living in five cities of Guangdong Province. Study participants’ sera were tested by horse red blood cells (RBCs) hemagglutination inhibition (HI) and microneutralization (MN) assays according to World Health Organization guidelines. The A/Jiangxi-Donghu/346-1/2013(H10N8) virus was used. Sera which have an HI assay ≥1:20 were further tested with the MN assay. Questionnaire data were examined for risk factor associations with positive serological assays. Risk factor analyses failed to identify specific factors associated with probable H10N8 infections. RESULTS: Among the 827 sera, only 21 animal workers had an HI titer ≥1:20 (18 had an HI titer of 1:20 and 3 had an HI titer of 1:40). None of these 21 subjects reported experiencing any influenza symptoms during the three months before enrollment. Among the three subjects with HI titers of 1:40, two had MN antibody titers of 1:40, and one had a MN antibody titer of 1:80 (probable H10N8 infections). CONCLUSIONS: Study data suggest that animal workers may have been infected with the H10N8 virus before the first recognized H10N8 human infection cases. It seems prudent to continue surveillance for H10N8 viruses among animal workers.",2014 Oct 27,"['Qi, Wenbao', 'Su, Shuo', 'Xiao, Chencheng', 'Zhou, Pei', 'Li, Huanan', 'Ke, Changwen', 'Gray, Gregory C', 'Zhang, Guihong', 'Liao, Ming']",BMC Med,,,True
5eba29203084de16f501b71b64873f5c96ce55f2,PMC,Toll-Like Receptor Responses to Peste des petits ruminants Virus in Goats and Water Buffalo,http://dx.doi.org/10.1371/journal.pone.0111609,PMC4219731,25369126,CC BY,"Ovine rinderpest or goat plague is an economically important and contagious viral disease of sheep and goats, caused by the Peste des petits ruminants virus (PPRV). Differences in susceptibility to goat plague among different breeds and water buffalo exist. The host innate immune system discriminates between pathogen associated molecular patterns and self antigens through surveillance receptors known as Toll like receptors (TLR). We investigated the role of TLR and cytokines in differential susceptibility of goat breeds and water buffalo to PPRV. We examined the replication of PPRV in peripheral blood mononuclear cells (PBMC) of Indian domestic goats and water buffalo and demonstrated that the levels of TLR3 and TLR7 and downstream signalling molecules correlation with susceptibility vs resistance. Naturally susceptible goat breeds, Barbari and Tellichery, had dampened innate immune responses to PPRV and increased viral loads with lower basal expression levels of TLR 3/7. Upon stimulation of PBMC with synthetic TLR3 and TLR7 agonists or PPRV, the levels of proinflammatory cytokines were found to be significantly higher while immunosuppressive interleukin (IL) 10 levels were lower in PPRV resistant Kanni and Salem Black breeds and water buffalo at transcriptional level, correlating with reduced viralloads in infected PBMC. Water buffalo produced higher levels of interferon (IFN) α in comparison with goats at transcriptional and translational levels. Pre-treatment of Vero cells with human IFNα resulted in reduction of PPRV replication, confirming the role of IFNα in limiting PPRV replication. Treatment with IRS66, a TLR7 antagonist, resulted in the reduction of IFNα levels, with increased PPRV replication confirming the role of TLR7. Single nucleotide polymorphism analysis of TLR7 of these goat breeds did not show any marked nucleotide differences that might account for susceptibility vs resistance to PPRV. Analyzing other host genetic factors might provide further insights on susceptibility to PPRV and genetic polymorphisms in the host.",2014 Nov 4,"['Dhanasekaran, Sakthivel', 'Biswas, Moanaro', 'Vignesh, Ambothi R.', 'Ramya, R.', 'Raj, Gopal Dhinakar', 'Tirumurugaan, Krishnaswamy G.', 'Raja, Angamuthu', 'Kataria, Ranjit S.', 'Parida, Satya', 'Subbiah, Elankumaran']",PLoS One,,,True
ff7d7dea55e89908b0a3935c6e5ce52cd8a165b4,PMC,Immunomodulatory Potential of Human Adipose Mesenchymal Stem Cells Derived Exosomes on in vitro Stimulated T Cells,http://dx.doi.org/10.3389/fimmu.2014.00556,PMC4220146,25414703,CC BY,"In the recent years, it has been demonstrated that the biological activity of mesenchymal stem cells (MSCs) is mediated through the release of paracrine factors. Many of these factors are released into exosomes, which are small membranous vesicles that participate in cell–cell communication. Exosomes from MSCs are thought to have similar functions to MSCs such as repairing and regeneration of damaged tissue, but little is known about the immunomodulatory effect of these vesicles. Based on an extensive bibliography where the immunomodulatory capacity of MSCs has been demonstrated, here we hypothesized that released exosomes from MSCs may have an immunomodulatory role on the differentiation, activation and function of different lymphocyte subsets. According to this hypothesis, in vitro experiments were performed to characterize the immunomodulatory effect of human adipose MSCs derived exosomes (exo-hASCs) on in vitro stimulated T cells. The phenotypic characterization of cytotoxic and helper T cells (activation and differentiation markers) together with functional assays (proliferation and IFN-γ production) demonstrated that exo-hASCs exerted an inhibitory effect in the differentiation and activation of T cells as well as a reduced T cell proliferation and IFN-γ release on in vitro stimulated cells. In summary, here we demonstrate that MSCs-derived exosomes are a cell-derived product that could be considered as a therapeutic agent for the treatment of inflammation-related diseases.",2014 Nov 4,"['Blazquez, Rebeca', 'Sanchez-Margallo, Francisco Miguel', 'de la Rosa, Olga', 'Dalemans, Wilfried', 'Álvarez, Verónica', 'Tarazona, Raquel', 'Casado, Javier G.']",Front Immunol,,,True
ae098292360fde9d65ff12d2beef927dff6c6077,PMC,Containing the accidental laboratory escape of potential pandemic influenza viruses,http://dx.doi.org/10.1186/1741-7015-11-252,PMC4220800,24283203,CC BY,"BACKGROUND: The recent work on the modified H5N1 has stirred an intense debate on the risk associated with the accidental release from biosafety laboratory of potential pandemic pathogens. Here, we assess the risk that the accidental escape of a novel transmissible influenza strain would not be contained in the local community. METHODS: We develop here a detailed agent-based model that specifically considers laboratory workers and their contacts in microsimulations of the epidemic onset. We consider the following non-pharmaceutical interventions: isolation of the laboratory, laboratory workers’ household quarantine, contact tracing of cases and subsequent household quarantine of identified secondary cases, and school and workplace closure both preventive and reactive. RESULTS: Model simulations suggest that there is a non-negligible probability (5% to 15%), strongly dependent on reproduction number and probability of developing clinical symptoms, that the escape event is not detected at all. We find that the containment depends on the timely implementation of non-pharmaceutical interventions and contact tracing and it may be effective (>90% probability per event) only for pathogens with moderate transmissibility (reproductive number no larger than R(0) = 1.5). Containment depends on population density and structure as well, with a probability of giving rise to a global event that is three to five times lower in rural areas. CONCLUSIONS: Results suggest that controllability of escape events is not guaranteed and, given the rapid increase of biosafety laboratories worldwide, this poses a serious threat to human health. Our findings may be relevant to policy makers when designing adequate preparedness plans and may have important implications for determining the location of new biosafety laboratories worldwide.",2013 Nov 28,"['Merler, Stefano', 'Ajelli, Marco', 'Fumanelli, Laura', 'Vespignani, Alessandro']",BMC Med,,,True
a9be3897c30e4a416d00398d86a623fc3d9faab5,PMC,Containing the accidental laboratory escape of potential pandemic influenza viruses,http://dx.doi.org/10.1186/1741-7015-11-252,PMC4220800,24283203,CC BY,"BACKGROUND: The recent work on the modified H5N1 has stirred an intense debate on the risk associated with the accidental release from biosafety laboratory of potential pandemic pathogens. Here, we assess the risk that the accidental escape of a novel transmissible influenza strain would not be contained in the local community. METHODS: We develop here a detailed agent-based model that specifically considers laboratory workers and their contacts in microsimulations of the epidemic onset. We consider the following non-pharmaceutical interventions: isolation of the laboratory, laboratory workers’ household quarantine, contact tracing of cases and subsequent household quarantine of identified secondary cases, and school and workplace closure both preventive and reactive. RESULTS: Model simulations suggest that there is a non-negligible probability (5% to 15%), strongly dependent on reproduction number and probability of developing clinical symptoms, that the escape event is not detected at all. We find that the containment depends on the timely implementation of non-pharmaceutical interventions and contact tracing and it may be effective (>90% probability per event) only for pathogens with moderate transmissibility (reproductive number no larger than R(0) = 1.5). Containment depends on population density and structure as well, with a probability of giving rise to a global event that is three to five times lower in rural areas. CONCLUSIONS: Results suggest that controllability of escape events is not guaranteed and, given the rapid increase of biosafety laboratories worldwide, this poses a serious threat to human health. Our findings may be relevant to policy makers when designing adequate preparedness plans and may have important implications for determining the location of new biosafety laboratories worldwide.",2013 Nov 28,"['Merler, Stefano', 'Ajelli, Marco', 'Fumanelli, Laura', 'Vespignani, Alessandro']",BMC Med,,,True
59af69dc1c698ba1b34d45b5a2e84302f0c1a907,PMC,MERS-CoV,http://dx.doi.org/10.1186/1471-2334-14-S2-S22,PMC4221070,,CC BY,,2014 May 23,"Müller, Marcel A",BMC Infect Dis,,,False
d0cb4b695a1cddbc249dcc8cb517441dea0157d6,PMC,Achieving compliance with the International Health Regulations by overseas territories of the United Kingdom of Great Britain and Northern Ireland,http://dx.doi.org/10.2471/BLT.14.137828,PMC4221769,25378745,CC BY,"The 2005 International Health Regulations (IHR) came into force for all Member States of the World Health Organization (WHO) in June 2007 and the deadline for achieving compliance was June 2012. The purpose of the IHR is to prevent, protect against, control – and provide a public health response to – international spread of disease. The territory of the United Kingdom of Great Britain and Northern Ireland and that of several other Member States, such as China, Denmark, France, the Netherlands and the United States of America, include overseas territories, which cover a total population of approximately 15 million people. Member States have a responsibility to ensure that all parts of their territory comply with the IHR. Since WHO has not provided specific guidance on compliance in the special circumstances of the overseas territories of Member States, compliance by these territories is an issue for self-assessment by Member States themselves. To date, no reports have been published on the assessment of IHR compliance in countries with overseas territories. We describe a gap analysis done in the United Kingdom to assess IHR compliance of its overseas territories. The findings and conclusions are broadly applicable to other countries with overseas territories which may have yet to assess their compliance with the IHR. Such assessments are needed to ensure compliance across all parts of a Member States’ territory and to increase global health security.",2014 Nov 1,"['Hamblion, Esther L', 'Salter, Mark', 'Jones, Jane', None]",Bull World Health Organ,,,True
64adce98190f9491944dc9d5141e0cccb6360519,PMC,Type I Interferon Regulates the Expression of Long Non-Coding RNAs,http://dx.doi.org/10.3389/fimmu.2014.00548,PMC4222131,25414701,CC BY,"Interferons (IFNs) are key players in the antiviral response. IFN sensing by the cell activates transcription of IFN-stimulated genes (ISGs) able to induce an antiviral state by affecting viral replication and release. IFN also induces the expression of ISGs that function as negative regulators to limit the strength and duration of IFN response. The ISGs identified so far belong to coding genes. However, only a small proportion of the transcriptome corresponds to coding transcripts and it has been estimated that there could be as many coding as long non-coding RNAs (lncRNAs). To address whether IFN can also regulate the expression of lncRNAs, we analyzed the transcriptome of HuH7 cells treated or not with IFNα2 by expression arrays. Analysis of the arrays showed increased levels of several well-characterized coding genes that respond to IFN both at early or late times. Furthermore, we identified several IFN-stimulated or -downregulated lncRNAs (ISRs and IDRs). Further validation showed that ISR2, 8, and 12 expression mimics that of their neighboring genes GBP1, IRF1, and IL6, respectively, all related to the IFN response. These genes are induced in response to different doses of IFNα2 in different cell lines at early (ISR2 or 8) or later (ISR12) time points. IFNβ also induced the expression of these lncRNAs. ISR2 and 8 were also induced by an influenza virus unable to block the IFN response but not by other wild-type lytic viruses tested. Surprisingly, both ISR2 and 8 were significantly upregulated in cultured cells and livers from patients infected with HCV. Increased levels of ISR2 were also detected in patients chronically infected with HIV. This is relevant as genome-wide guilt-by-association studies predict that ISR2, 8, and 12 may function in viral processes, in the IFN pathway and the antiviral response. Therefore, we propose that these lncRNAs could be induced by IFN to function as positive or negative regulators of the antiviral response.",2014 Nov 6,"['Carnero, Elena', 'Barriocanal, Marina', 'Segura, Victor', 'Guruceaga, Elizabeth', 'Prior, Celia', 'Börner, Kathleen', 'Grimm, Dirk', 'Fortes, Puri']",Front Immunol,,,True
538d34ee99bf5a6c75bc18a2749e0aff5ce72d35,PMC,Patterns of between-farm contacts via professionals in Sweden,http://dx.doi.org/10.1186/s13028-014-0070-2,PMC4222379,25366065,CC BY,"BACKGROUND: Infectious diseases of livestock have negative consequences for animal production as well as animal health and welfare and can be transmitted between farms via direct (live animal movements) as well as indirect (via physical vectors such as, people, transport vehicles and fomites) contacts. The objective of the study was to examine the travel patterns of professionals visiting Swedish farms (veterinarians, milk tanker drivers, artificial inseminators, maintenance technicians and livestock hauliers). This was done by obtaining records of the farms visited by a sample of professionals in the above categories in one week in January, one week in April, one week in July and one week in October in the Swedish counties Västerbotten, Södermanland, Västergötland and Skåne. RESULTS: There were twelve participating organisations, and data was provided for one to three individuals/vehicles/veterinary practices per professional category and per geographic region (except for dairy service technicians and livestock hauliers who did not provide data from all regions). There was a trend towards larger areas covered and smaller number of farms visited per week in the north, but exceptions occurred and there were regional variations. Generally, the greatest areas were travelled by milk tankers and livestock hauliers, and the profession travelling over the smallest areas tended to be the veterinarians. Milk tankers visited most farms per week, one milk tanker could visit between 23 and 90 farms per week and travel over areas between 717 km(2) and 23,512 km(2) per week. CONCLUSIONS: Valuable insight into the travel patterns of Swedish professionals has emerged although the implications of the study largely concern highly infectious diseases. Movement of live animals pose the greatest risk for the spread of infectious animal diseases; however indirect contacts are important for many diseases. The results of this study indicate that in Sweden a highly contagious disease might spread over a large area in the time span of one incubation period, which ought to be kept in mind in case of an outbreak and in outbreak investigations. The difficulties in contacting some professionals visiting farms could be a problem in an outbreak situation.",2014 Nov 4,"['Olofsson, Emelie', 'Nöremark, Maria', 'Lewerin, Susanna Sternberg']",Acta Vet Scand,,,True
d1465b112750748b01edc7837f005803a6e87658,PMC,Escherichia coli YmdB regulates biofilm formation independently of its role as an RNase III modulator,http://dx.doi.org/10.1186/1471-2180-13-266,PMC4222554,24267348,CC BY,"BACKGROUND: Ribonuclease III (RNase III) activity modulates hundreds of genes in Escherichia coli (E. coli). YmdB, a member of the macrodomain protein family, is one of known trans-acting regulators of RNase III activity; however, the significance of its regulatory role in specific bacterial cellular processes and related genes has not been determined. YmdB overexpression was used to model YmdB-induced RNase III inhibition in vivo, and microarray analysis identified gene targets and cellular processes related to RNase III inhibition. RESULTS: The expression of >2,000 E. coli genes was modulated by YmdB induction; 129 genes were strongly regulated, of which 80 have not been reported as RNase III targets. Of these, ten are involved in biofilm formation. Significantly, YmdB overexpression also inhibited biofilm formation via a process that is not uniquely dependent upon RNase III inhibition. Moreover, biofilm formation is interdependently regulated by RpoS, a known stress response regulator and biofilm inhibitor, and by YmdB. CONCLUSIONS: This is the first global profile of target genes modulated by YmdB-induced RNase III inhibition in E. coli, and the data reveal a novel, hitherto unrecognized regulatory role for YmdB in biofilm modulation.",2013 Nov 24,"['Kim, Taeyeon', 'Lee, Juyeon', 'Kim, Kwang-sun']",BMC Microbiol,,,True
a1cc5852e148a66c7044a68bef5d6e9323fb4a99,PMC,Escherichia coli YmdB regulates biofilm formation independently of its role as an RNase III modulator,http://dx.doi.org/10.1186/1471-2180-13-266,PMC4222554,24267348,CC BY,"BACKGROUND: Ribonuclease III (RNase III) activity modulates hundreds of genes in Escherichia coli (E. coli). YmdB, a member of the macrodomain protein family, is one of known trans-acting regulators of RNase III activity; however, the significance of its regulatory role in specific bacterial cellular processes and related genes has not been determined. YmdB overexpression was used to model YmdB-induced RNase III inhibition in vivo, and microarray analysis identified gene targets and cellular processes related to RNase III inhibition. RESULTS: The expression of >2,000 E. coli genes was modulated by YmdB induction; 129 genes were strongly regulated, of which 80 have not been reported as RNase III targets. Of these, ten are involved in biofilm formation. Significantly, YmdB overexpression also inhibited biofilm formation via a process that is not uniquely dependent upon RNase III inhibition. Moreover, biofilm formation is interdependently regulated by RpoS, a known stress response regulator and biofilm inhibitor, and by YmdB. CONCLUSIONS: This is the first global profile of target genes modulated by YmdB-induced RNase III inhibition in E. coli, and the data reveal a novel, hitherto unrecognized regulatory role for YmdB in biofilm modulation.",2013 Nov 24,"['Kim, Taeyeon', 'Lee, Juyeon', 'Kim, Kwang-sun']",BMC Microbiol,,,False
e47f91345fe98307b49fc5f39aa5f781ec37f893,PMC,Specificity and Effector Functions of Human RSV-Specific IgG from Bovine Milk,http://dx.doi.org/10.1371/journal.pone.0112047,PMC4222812,25375837,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) infection is the second most important cause of death in the first year of life, and early RSV infections are associated with the development of asthma. Breastfeeding and serum IgG have been shown to protect against RSV infection. Yet, many infants depend on bovine milk-based nutrition, which at present lacks intact immunoglobulins. OBJECTIVE: To investigate whether IgG purified from bovine milk (bIgG) can modulate immune responses against human RSV. METHODS: ELISAs were performed to analyse binding of bIgG to human respiratory pathogens. bIgG or hRSV was coated to plates to assess dose-dependent binding of bIgG to human Fcγ receptors (FcγR) or bIgG-mediated binding of myeloid cells to hRSV respectively. S. Epidermidis and RSV were used to test bIgG-mediated binding and internalisation of pathogens by myeloid cells. Finally, the ability of bIgG to neutralise infection of HEp2 cells by hRSV was evaluated. RESULTS: bIgG recognised human RSV, influenza haemagglutinin and Haemophilus influenza. bIgG bound to FcγRII on neutrophils, monocytes and macrophages, but not to FcγRI and FcγRIII, and could bind simultaneously to hRSV and human FcγRII on neutrophils. In addition, human neutrophils and dendritic cells internalised pathogens that were opsonised with bIgG. Finally, bIgG could prevent infection of HEp2 cells by hRSV. CONCLUSIONS: The data presented here show that bIgG binds to hRSV and other human respiratory pathogens and induces effector functions through binding to human FcγRII on phagocytes. Thus bovine IgG may contribute to immune protection against RSV.",2014 Nov 6,"['den Hartog, Gerco', 'Jacobino, Shamir', 'Bont, Louis', 'Cox, Linda', 'Ulfman, Laurien H.', 'Leusen, Jeanette H. W.', 'van Neerven, R. J. Joost']",PLoS One,,,True
2c33d7f0e90a4a8a7e7be1d56308496b7e13dad5,PMC,"Symptomatic treatment of the common cold with a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine: a randomized, placebo-controlled trial",http://dx.doi.org/10.1186/1471-2334-13-556,PMC4222817,24261438,CC BY,"BACKGROUND: The common cold and other viral airway infections are highly prevalent in the population, and their treatment often requires the use of medications for symptomatic relief. Paracetamol is as an analgesic and antipyretic; chlorphenamine is an antihistamine; and phenylephrine, a vasoconstrictor and decongestant. This randomized, double-blind, placebo-controlled trial sought to evaluate the efficacy and safety of a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine in the symptomatic treatment of the common cold and flu-like syndrome in adults. METHODS: This study enrolled 146 individuals aged 18 to 60 years who had moderate to severe flu-like syndrome or common cold. After clinical examination and laboratory tests, individuals were randomly assigned to receive the fixed-dose combination (73) or placebo (73), five capsules per day for 48 to 72 hours. The primary efficacy endpoint was the sum of the scores of 10 symptoms on a four-point Likert-type scale. To evaluate treatment safety, the occurrence of adverse events was also measured. RESULTS: Mean age was 33.5 (±9.5) years in the placebo group and 33.8 (±11.5) in the treatment group. There were 55 women and 18 men in the placebo group, and 46 women and 27 men in the treatment group. Comparison of overall symptom scores in the two groups revealed a significantly greater reduction in the treatment group than in the placebo group (p = 0.015). Analysis at the first 13 dose intervals (± 66 h of treatment) showed a greater reduction of symptom scores in the treatment group than in the placebo group (p < 0.05). The number and distribution of adverse events were similar in both groups. CONCLUSION: A fixed-dose combination of paracetamol, chlorphenamine and phenylephrine was safe and more effective than placebo in the symptomatic treatment of the common cold or flu-like syndrome in adults. TRIAL REGISTRATION: NCT01389518",2013 Nov 22,"['Picon, Paulo Dornelles', 'Costa, Marisa Boff', 'da Veiga Picon, Rafael', 'Fendt, Lucia Costa Cabral', 'Suksteris, Maurício Leichter', 'Saccilotto, Indara Carmanim', 'Dornelles, Alicia Dorneles', 'Schmidt, Luis Felipe Carissimi']",BMC Infect Dis,,,True
e5ca488c67d3b9db4056f7fe900e10254d69f7ca,PMC,The Evolution and Genetics of Virus Host Shifts,http://dx.doi.org/10.1371/journal.ppat.1004395,PMC4223060,25375777,CC BY,"Emerging viral diseases are often the product of a host shift, where a pathogen jumps from its original host into a novel species. Phylogenetic studies show that host shifts are a frequent event in the evolution of most pathogens, but why pathogens successfully jump between some host species but not others is only just becoming clear. The susceptibility of potential new hosts can vary enormously, with close relatives of the natural host typically being the most susceptible. Often, pathogens must adapt to successfully infect a novel host, for example by evolving to use different cell surface receptors, to escape the immune response, or to ensure they are transmitted by the new host. In viruses there are often limited molecular solutions to achieve this, and the same sequence changes are often seen each time a virus infects a particular host. These changes may come at a cost to other aspects of the pathogen's fitness, and this may sometimes prevent host shifts from occurring. Here we examine how these evolutionary factors affect patterns of host shifts and disease emergence.",2014 Nov 6,"['Longdon, Ben', 'Brockhurst, Michael A.', 'Russell, Colin A.', 'Welch, John J.', 'Jiggins, Francis M.']",PLoS Pathog,,,True
3339f4bb346bfa3070ae5fc7dc745ef051535b0e,PMC,Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner,http://dx.doi.org/10.1371/journal.ppat.1004502,PMC4223067,25375324,CC BY,"Enveloped viruses need to fuse with a host cell membrane in order to deliver their genome into the host cell. While some viruses fuse with the plasma membrane, many viruses are endocytosed prior to fusion. Specific cues in the endosomal microenvironment induce conformational changes in the viral fusion proteins leading to viral and host membrane fusion. In the present study we investigated the entry of coronaviruses (CoVs). Using siRNA gene silencing, we found that proteins known to be important for late endosomal maturation and endosome-lysosome fusion profoundly promote infection of cells with mouse hepatitis coronavirus (MHV). Using recombinant MHVs expressing reporter genes as well as a novel, replication-independent fusion assay we confirmed the importance of clathrin-mediated endocytosis and demonstrated that trafficking of MHV to lysosomes is required for fusion and productive entry to occur. Nevertheless, MHV was shown to be less sensitive to perturbation of endosomal pH than vesicular stomatitis virus and influenza A virus, which fuse in early and late endosomes, respectively. Our results indicate that entry of MHV depends on proteolytic processing of its fusion protein S by lysosomal proteases. Fusion of MHV was severely inhibited by a pan-lysosomal protease inhibitor, while trafficking of MHV to lysosomes and processing by lysosomal proteases was no longer required when a furin cleavage site was introduced in the S protein immediately upstream of the fusion peptide. Also entry of feline CoV was shown to depend on trafficking to lysosomes and processing by lysosomal proteases. In contrast, MERS-CoV, which contains a minimal furin cleavage site just upstream of the fusion peptide, was negatively affected by inhibition of furin, but not of lysosomal proteases. We conclude that a proteolytic cleavage site in the CoV S protein directly upstream of the fusion peptide is an essential determinant of the intracellular site of fusion.",2014 Nov 6,"['Burkard, Christine', 'Verheije, Monique H.', 'Wicht, Oliver', 'van Kasteren, Sander I.', 'van Kuppeveld, Frank J.', 'Haagmans, Bart L.', 'Pelkmans, Lucas', 'Rottier, Peter J. M.', 'Bosch, Berend Jan', 'de Haan, Cornelis A. M.']",PLoS Pathog,,,True
9faf9327f699f47d3a08625a86ee07af1402f3c5,PMC,Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner,http://dx.doi.org/10.1371/journal.ppat.1004502,PMC4223067,25375324,CC BY,"Enveloped viruses need to fuse with a host cell membrane in order to deliver their genome into the host cell. While some viruses fuse with the plasma membrane, many viruses are endocytosed prior to fusion. Specific cues in the endosomal microenvironment induce conformational changes in the viral fusion proteins leading to viral and host membrane fusion. In the present study we investigated the entry of coronaviruses (CoVs). Using siRNA gene silencing, we found that proteins known to be important for late endosomal maturation and endosome-lysosome fusion profoundly promote infection of cells with mouse hepatitis coronavirus (MHV). Using recombinant MHVs expressing reporter genes as well as a novel, replication-independent fusion assay we confirmed the importance of clathrin-mediated endocytosis and demonstrated that trafficking of MHV to lysosomes is required for fusion and productive entry to occur. Nevertheless, MHV was shown to be less sensitive to perturbation of endosomal pH than vesicular stomatitis virus and influenza A virus, which fuse in early and late endosomes, respectively. Our results indicate that entry of MHV depends on proteolytic processing of its fusion protein S by lysosomal proteases. Fusion of MHV was severely inhibited by a pan-lysosomal protease inhibitor, while trafficking of MHV to lysosomes and processing by lysosomal proteases was no longer required when a furin cleavage site was introduced in the S protein immediately upstream of the fusion peptide. Also entry of feline CoV was shown to depend on trafficking to lysosomes and processing by lysosomal proteases. In contrast, MERS-CoV, which contains a minimal furin cleavage site just upstream of the fusion peptide, was negatively affected by inhibition of furin, but not of lysosomal proteases. We conclude that a proteolytic cleavage site in the CoV S protein directly upstream of the fusion peptide is an essential determinant of the intracellular site of fusion.",2014 Nov 6,"['Burkard, Christine', 'Verheije, Monique H.', 'Wicht, Oliver', 'van Kasteren, Sander I.', 'van Kuppeveld, Frank J.', 'Haagmans, Bart L.', 'Pelkmans, Lucas', 'Rottier, Peter J. M.', 'Bosch, Berend Jan', 'de Haan, Cornelis A. M.']",PLoS Pathog,,,False
96456a955d56878dc1e53c0feeb14bf307518b17,PMC,Programmed Ribosomal Frameshift Alters Expression of West Nile Virus Genes and Facilitates Virus Replication in Birds and Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004447,PMC4223154,25375107,CC0,"West Nile virus (WNV) is a human pathogen of significant medical importance with close to 40,000 cases of encephalitis and more than 1,600 deaths reported in the US alone since its first emergence in New York in 1999. Previous studies identified a motif in the beginning of non-structural gene NS2A of encephalitic flaviviruses including WNV which induces programmed −1 ribosomal frameshift (PRF) resulting in production of an additional NS protein NS1′. We have previously demonstrated that mutant WNV with abolished PRF was attenuated in mice. Here we have extended our previous observations by showing that PRF does not appear to have a significant role in virus replication, virion formation, and viral spread in several cell lines in vitro. However, we have also shown that PRF induces an over production of structural proteins over non-structural proteins in virus-infected cells and that mutation abolishing PRF is present in ∼11% of the wild type virus population. In vivo experiments in house sparrows using wild type and PRF mutant of New York 99 strain of WNV viruses showed some attenuation for the PRF mutant virus. Moreover, PRF mutant of Kunjin strain of WNV showed significant decrease compared to wild type virus infection in dissemination of the virus from the midgut through the haemocoel, and ultimately the capacity of infected mosquitoes to transmit virus. Thus our results demonstrate an important role for PRF in regulating expression of viral genes and consequently virus replication in avian and mosquito hosts.",2014 Nov 6,"['Melian, Ezequiel Balmori', 'Hall-Mendelin, Sonja', 'Du, Fangyao', 'Owens, Nick', 'Bosco-Lauth, Angela M.', 'Nagasaki, Tomoko', 'Rudd, Stephen', 'Brault, Aaron C.', 'Bowen, Richard A.', 'Hall, Roy A.', 'van den Hurk, Andrew F.', 'Khromykh, Alexander A.']",PLoS Pathog,,,True
9484a7c6359d1364cd37bb1d80bdefd118d7ffe6,PMC,Viruses and viral proteins,http://dx.doi.org/10.1107/S205225251402003X,PMC4224467,25485129,CC BY,"For more than 30 years X-ray crystallography has been by far the most powerful approach for determining the structures of viruses and viral proteins at atomic resolution. The information provided by these structures, which covers many important aspects of the viral life cycle such as cell-receptor recognition, viral entry, nucleic acid transfer and genome replication, has extensively enriched our vision of the virus world. Many of the structures available correspond to potential targets for antiviral drugs against important human pathogens. This article provides an overview of the current knowledge of different structural aspects of the above-mentioned processes.",2014 Oct 14,"['Verdaguer, Nuria', 'Ferrero, Diego', 'Murthy, Mathur R. N.']",IUCrJ,,,True
6086be90c6e06e3fcbef307a61c0563e029ee24d,PMC,Bordetella pertussis in infants hospitalized for acute respiratory symptoms remains a concern,http://dx.doi.org/10.1186/1471-2334-13-526,PMC4226035,24209790,CC BY,"BACKGROUND: Preliminary results suggest that pertussis infection might be considered in infants during a seasonal respiratory syncytial virus (RSV) outbreak. METHODS: In order to analyze clinical features and laboratory findings in infants with pertussis hospitalized for acute respiratory symptoms during a seasonal RSV outbreak, we conducted a retrospective single-center study on 19 infants with pertussis (6 boys; median age 72 days) and 19 matched controls (RSV-bronchiolitis), hospitalized from October 2008 to April 2010. B. pertussis and RSV were detected from nasopharyngeal washes with Real Time-PCR. RESULTS: Infants with pertussis were less often breastfeed than infants with RSV bronchiolitis (63.2% vs 89.5%; p <0.06). Clinically, significantly fewer infants with pertussis than controls had more episodes of whooping cough (63.2% vs 0.0%; p < 0.001) and also less frequently fever at admission (15.8% vs 68.4%; p <0.01), apnea (52.6% vs 10.5%; p <0.006), and cyanosis (52.6% vs 10.5%; p < 0.006). Infants with pertussis had more often no abnormal chest sounds on auscultation than infants with RSV bronchiolitis (0% vs 42,1%; p < 0.005). The absolute blood lymphocyte and eosinophil counts were higher in infants with B. pertussis than in controls with bronchiolitis (23886 ± 16945 vs 10725 ± 4126 cells/mm(3), p < 0.0001 and 13.653 ± 10.430 vs 4.730 ± 2.400 cells/mm(3), p < 0.001). The molecular analysis of 2 B. pertussis isolates for ptxA1, ptxP3, and prn2 genes showed the presence of gene variants. CONCLUSIONS: When infants are hospitalized for acute respiratory symptoms, physicians should suspect a pertussis infection, seek for specific clinical symptoms, investigate lymphocyte and eosinophil counts and thus diagnose infection early enough to allow treatment.",2013 Nov 8,"['Nicolai, Ambra', 'Nenna, Raffaella', 'Stefanelli, Paola', 'Carannante, Anna', 'Schiavariello, Concetta', 'Pierangeli, Alessandra', 'Scagnolari, Carolina', 'Moretti, Corrado', 'Papoff, Paola', 'Bonci, Enea', 'Ferrara, Marianna', 'Papasso, Stefano', 'Midulla, Fabio']",BMC Infect Dis,,,True
ab3cd83b4fa77a65b99102d3d9afcfe861bdb2c4,PMC,"Simulate_PCR for amplicon prediction and annotation from multiplex, degenerate primers and probes",http://dx.doi.org/10.1186/1471-2105-15-237,PMC4226945,25005023,CC BY,"BACKGROUND: Pairing up primers to amplify desired targets and avoid undesired cross reactions can be a combinatorial challenge. Effective prediction of specificity and inclusivity from multiplexed primers and TaqMan®/Luminex® probes is a critical step in PCR design. RESULTS: Code is described to identify all primer and probe combinations from a list of unpaired, unordered candidates that should produce a product. It predicts and extracts all amplicon sequences in a large sequence database from a list of primers and probes, allowing degenerate bases and user-specified levels of primer-target mismatch tolerance. Amplicons hit by TaqMan®/Luminex® probes are indicated, and products may be annotated with gene information from NCBI. Fragment length distributions are calculated to predict electrophoretic gel banding patterns. CONCLUSIONS: Simulate_PCR is the only freely available software that can be run from the command line for high throughput applications which can calculate all products from large lists of primers and probes compared to a large sequence database such as nt. It requires no prior knowledge of how primers should be paired. Degenerate bases are allowed and entire amplicon sequences are extracted and annotated with gene information. Examples are provided for sets of TaqMan®/Luminex® PCR signatures predicted to amplify all HIV-1 genomes, all Coronaviridae genomes, and a group of antibiotic resistance genes. The software is a command line perl script freely available as open source.",2014 Jul 9,"['Gardner, Shea N', 'Slezak, Tom']",BMC Bioinformatics,,,True
a3bf6f0444bb71c6d5b232122353d551a15d0a5f,PMC,Archaeal DnaG contains a conserved N-terminal RNA-binding domain and enables tailing of rRNA by the exosome,http://dx.doi.org/10.1093/nar/gku969,PMC4227792,25326320,CC BY,"The archaeal exosome is a phosphorolytic 3′–5′ exoribonuclease complex. In a reverse reaction it synthesizes A-rich RNA tails. Its RNA-binding cap comprises the eukaryotic orthologs Rrp4 and Csl4, and an archaea-specific subunit annotated as DnaG. In Sulfolobus solfataricus DnaG and Rrp4 but not Csl4 show preference for poly(rA). Archaeal DnaG contains N- and C-terminal domains (NTD and CTD) of unknown function flanking a TOPRIM domain. We found that the NT and TOPRIM domains have comparable, high conservation in all archaea, while the CTD conservation correlates with the presence of exosome. We show that the NTD is a novel RNA-binding domain with poly(rA)-preference cooperating with the TOPRIM domain in binding of RNA. Consistently, a fusion protein containing full-length Csl4 and NTD of DnaG led to enhanced degradation of A-rich RNA by the exosome. We also found that DnaG strongly binds native and in vitro transcribed rRNA and enables its polynucleotidylation by the exosome. Furthermore, rRNA-derived transcripts with heteropolymeric tails were degraded faster by the exosome than their non-tailed variants. Based on our data, we propose that archaeal DnaG is an RNA-binding protein, which, in the context of the exosome, is involved in targeting of stable RNA for degradation.",2014 Nov 10,"['Hou, Linlin', 'Klug, Gabriele', 'Evguenieva-Hackenberg, Elena']",Nucleic Acids Res,,,True
6056125fa915e5c43fae515aa0813c1583262f68,PMC,Archaeal DnaG contains a conserved N-terminal RNA-binding domain and enables tailing of rRNA by the exosome,http://dx.doi.org/10.1093/nar/gku969,PMC4227792,25326320,CC BY,"The archaeal exosome is a phosphorolytic 3′–5′ exoribonuclease complex. In a reverse reaction it synthesizes A-rich RNA tails. Its RNA-binding cap comprises the eukaryotic orthologs Rrp4 and Csl4, and an archaea-specific subunit annotated as DnaG. In Sulfolobus solfataricus DnaG and Rrp4 but not Csl4 show preference for poly(rA). Archaeal DnaG contains N- and C-terminal domains (NTD and CTD) of unknown function flanking a TOPRIM domain. We found that the NT and TOPRIM domains have comparable, high conservation in all archaea, while the CTD conservation correlates with the presence of exosome. We show that the NTD is a novel RNA-binding domain with poly(rA)-preference cooperating with the TOPRIM domain in binding of RNA. Consistently, a fusion protein containing full-length Csl4 and NTD of DnaG led to enhanced degradation of A-rich RNA by the exosome. We also found that DnaG strongly binds native and in vitro transcribed rRNA and enables its polynucleotidylation by the exosome. Furthermore, rRNA-derived transcripts with heteropolymeric tails were degraded faster by the exosome than their non-tailed variants. Based on our data, we propose that archaeal DnaG is an RNA-binding protein, which, in the context of the exosome, is involved in targeting of stable RNA for degradation.",2014 Nov 10,"['Hou, Linlin', 'Klug, Gabriele', 'Evguenieva-Hackenberg, Elena']",Nucleic Acids Res,,,False
08c1093aa1c393ee5364089d26278781dc3a3405,PMC,Mapping overlapping functional elements embedded within the protein-coding regions of RNA viruses,http://dx.doi.org/10.1093/nar/gku981,PMC4227794,25326325,CC BY,"Identification of the full complement of genes and other functional elements in any virus is crucial to fully understand its molecular biology and guide the development of effective control strategies. RNA viruses have compact multifunctional genomes that frequently contain overlapping genes and non-coding functional elements embedded within protein-coding sequences. Overlapping features often escape detection because it can be difficult to disentangle the multiple roles of the constituent nucleotides via mutational analyses, while high-throughput experimental techniques are often unable to distinguish functional elements from incidental features. However, RNA viruses evolve very rapidly so that, even within a single species, substitutions rapidly accumulate at neutral or near-neutral sites providing great potential for comparative genomics to distinguish the signature of purifying selection. Computationally identified features can then be efficiently targeted for experimental analysis. Here we analyze alignments of protein-coding virus sequences to identify regions where there is a statistically significant reduction in the degree of variability at synonymous sites, a characteristic signature of overlapping functional elements. Having previously tested this technique by experimental verification of discoveries in selected viruses, we now analyze sequence alignments for ∼700 RNA virus species to identify hundreds of such regions, many of which have not been previously described.",2014 Nov 10,"Firth, Andrew E.",Nucleic Acids Res,,,True
ed745dd99691994096cdc638c5398cd65a2c9539,PMC,Mapping overlapping functional elements embedded within the protein-coding regions of RNA viruses,http://dx.doi.org/10.1093/nar/gku981,PMC4227794,25326325,CC BY,"Identification of the full complement of genes and other functional elements in any virus is crucial to fully understand its molecular biology and guide the development of effective control strategies. RNA viruses have compact multifunctional genomes that frequently contain overlapping genes and non-coding functional elements embedded within protein-coding sequences. Overlapping features often escape detection because it can be difficult to disentangle the multiple roles of the constituent nucleotides via mutational analyses, while high-throughput experimental techniques are often unable to distinguish functional elements from incidental features. However, RNA viruses evolve very rapidly so that, even within a single species, substitutions rapidly accumulate at neutral or near-neutral sites providing great potential for comparative genomics to distinguish the signature of purifying selection. Computationally identified features can then be efficiently targeted for experimental analysis. Here we analyze alignments of protein-coding virus sequences to identify regions where there is a statistically significant reduction in the degree of variability at synonymous sites, a characteristic signature of overlapping functional elements. Having previously tested this technique by experimental verification of discoveries in selected viruses, we now analyze sequence alignments for ∼700 RNA virus species to identify hundreds of such regions, many of which have not been previously described.",2014 Nov 10,"Firth, Andrew E.",Nucleic Acids Res,,,True
7dfaa4c09d874ca072da1848411baba5c552b8f9,PMC,G-quadruplexes in viruses: function and potential therapeutic applications,http://dx.doi.org/10.1093/nar/gku999,PMC4227801,25332402,CC BY,"G-rich nucleic acids can form non-canonical G-quadruplex structures (G4s) in which four guanines fold in a planar arrangement through Hoogsteen hydrogen bonds. Although many biochemical and structural studies have focused on DNA sequences containing successive, adjacent guanines that spontaneously fold into G4s, evidence for their in vivo relevance has recently begun to accumulate. Complete sequencing of the human genome highlighted the presence of ∼300 000 sequences that can potentially form G4s. Likewise, the presence of putative G4-sequences has been reported in various viruses genomes [e.g., Human immunodeficiency virus (HIV-1), Epstein–Barr virus (EBV), papillomavirus (HPV)]. Many studies have focused on telomeric G4s and how their dynamics are regulated to enable telomere synthesis. Moreover, a role for G4s has been proposed in cellular and viral replication, recombination and gene expression control. In parallel, DNA aptamers that form G4s have been described as inhibitors and diagnostic tools to detect viruses [e.g., hepatitis A virus (HAV), EBV, cauliflower mosaic virus (CaMV), severe acute respiratory syndrome virus (SARS), simian virus 40 (SV40)]. Here, special emphasis will be given to the possible role of these structures in a virus life cycle as well as the use of G4-forming oligonucleotides as potential antiviral agents and innovative tools.",2014 Nov 10,"['Métifiot, Mathieu', 'Amrane, Samir', 'Litvak, Simon', 'Andreola, Marie-Line']",Nucleic Acids Res,,,True
c992817218f27eaa39a7bc3b90e9bd0538017eb0,PMC,Applying evolutionary concepts to wildlife disease ecology and management,http://dx.doi.org/10.1111/eva.12168,PMC4227862,25469163,CC BY,"Existing and emerging infectious diseases are among the most pressing global threats to biodiversity, food safety and human health. The complex interplay between host, pathogen and environment creates a challenge for conserving species, communities and ecosystem functions, while mediating the many known ecological and socio-economic negative effects of disease. Despite the clear ecological and evolutionary contexts of host–pathogen dynamics, approaches to managing wildlife disease remain predominantly reactionary, focusing on surveillance and some attempts at eradication. A few exceptional studies have heeded recent calls for better integration of ecological concepts in the study and management of wildlife disease; however, evolutionary concepts remain underused. Applied evolution consists of four principles: evolutionary history, genetic and phenotypic variation, selection and eco-evolutionary dynamics. In this article, we first update a classical framework for understanding wildlife disease to integrate better these principles. Within this framework, we explore the evolutionary implications of environment–disease interactions. Subsequently, we synthesize areas where applied evolution can be employed in wildlife disease management. Finally, we discuss some future directions and challenges. Here, we underscore that despite some evolutionary principles currently playing an important role in our understanding of disease in wild animals, considerable opportunities remain for fostering the practice of evolutionarily enlightened wildlife disease management.",2014 Aug 31,"['Vander Wal, Eric', 'Garant, Dany', 'Calmé, Sophie', 'Chapman, Colin A', 'Festa-Bianchet, Marco', 'Millien, Virginie', 'Rioux-Paquette, Sébastien', 'Pelletier, Fanie']",Evol Appl,,,True
7f8fc0ff30e4455d834e829db27b8d529b2920df,PMC,Automated analysis of phylogenetic clusters,http://dx.doi.org/10.1186/1471-2105-14-317,PMC4228337,24191891,CC BY,"BACKGROUND: As sequence data sets used for the investigation of pathogen transmission patterns increase in size, automated tools and standardized methods for cluster analysis have become necessary. We have developed an automated Cluster Picker which identifies monophyletic clades meeting user-input criteria for bootstrap support and maximum genetic distance within large phylogenetic trees. A second tool, the Cluster Matcher, automates the process of linking genetic data to epidemiological or clinical data, and matches clusters between runs of the Cluster Picker. RESULTS: We explore the effect of different bootstrap and genetic distance thresholds on clusters identified in a data set of publicly available HIV sequences, and compare these results to those of a previously published tool for cluster identification. To demonstrate their utility, we then use the Cluster Picker and Cluster Matcher together to investigate how clusters in the data set changed over time. We find that clusters containing sequences from more than one UK location at the first time point (multiple origin) were significantly more likely to grow than those representing only a single location. CONCLUSIONS: The Cluster Picker and Cluster Matcher can rapidly process phylogenetic trees containing tens of thousands of sequences. Together these tools will facilitate comparisons of pathogen transmission dynamics between studies and countries.",2013 Nov 6,"['Ragonnet-Cronin, Manon', 'Hodcroft, Emma', 'Hué, Stéphane', 'Fearnhill, Esther', 'Delpech, Valerie', 'Brown, Andrew J Leigh', 'Lycett, Samantha']",BMC Bioinformatics,,,True
62a1f5bb2940b4c4c29338c8f9fc47fd431aed28,PMC,Automated analysis of phylogenetic clusters,http://dx.doi.org/10.1186/1471-2105-14-317,PMC4228337,24191891,CC BY,"BACKGROUND: As sequence data sets used for the investigation of pathogen transmission patterns increase in size, automated tools and standardized methods for cluster analysis have become necessary. We have developed an automated Cluster Picker which identifies monophyletic clades meeting user-input criteria for bootstrap support and maximum genetic distance within large phylogenetic trees. A second tool, the Cluster Matcher, automates the process of linking genetic data to epidemiological or clinical data, and matches clusters between runs of the Cluster Picker. RESULTS: We explore the effect of different bootstrap and genetic distance thresholds on clusters identified in a data set of publicly available HIV sequences, and compare these results to those of a previously published tool for cluster identification. To demonstrate their utility, we then use the Cluster Picker and Cluster Matcher together to investigate how clusters in the data set changed over time. We find that clusters containing sequences from more than one UK location at the first time point (multiple origin) were significantly more likely to grow than those representing only a single location. CONCLUSIONS: The Cluster Picker and Cluster Matcher can rapidly process phylogenetic trees containing tens of thousands of sequences. Together these tools will facilitate comparisons of pathogen transmission dynamics between studies and countries.",2013 Nov 6,"['Ragonnet-Cronin, Manon', 'Hodcroft, Emma', 'Hué, Stéphane', 'Fearnhill, Esther', 'Delpech, Valerie', 'Brown, Andrew J Leigh', 'Lycett, Samantha']",BMC Bioinformatics,,,True
0c59c6dbfbf29fb7f0872efe3204551c75f79d02,PMC,Automated analysis of phylogenetic clusters,http://dx.doi.org/10.1186/1471-2105-14-317,PMC4228337,24191891,CC BY,"BACKGROUND: As sequence data sets used for the investigation of pathogen transmission patterns increase in size, automated tools and standardized methods for cluster analysis have become necessary. We have developed an automated Cluster Picker which identifies monophyletic clades meeting user-input criteria for bootstrap support and maximum genetic distance within large phylogenetic trees. A second tool, the Cluster Matcher, automates the process of linking genetic data to epidemiological or clinical data, and matches clusters between runs of the Cluster Picker. RESULTS: We explore the effect of different bootstrap and genetic distance thresholds on clusters identified in a data set of publicly available HIV sequences, and compare these results to those of a previously published tool for cluster identification. To demonstrate their utility, we then use the Cluster Picker and Cluster Matcher together to investigate how clusters in the data set changed over time. We find that clusters containing sequences from more than one UK location at the first time point (multiple origin) were significantly more likely to grow than those representing only a single location. CONCLUSIONS: The Cluster Picker and Cluster Matcher can rapidly process phylogenetic trees containing tens of thousands of sequences. Together these tools will facilitate comparisons of pathogen transmission dynamics between studies and countries.",2013 Nov 6,"['Ragonnet-Cronin, Manon', 'Hodcroft, Emma', 'Hué, Stéphane', 'Fearnhill, Esther', 'Delpech, Valerie', 'Brown, Andrew J Leigh', 'Lycett, Samantha']",BMC Bioinformatics,,,False
f47e681d9221b89b8872886fc50a7ec0f411f799,PMC,Automated analysis of phylogenetic clusters,http://dx.doi.org/10.1186/1471-2105-14-317,PMC4228337,24191891,CC BY,"BACKGROUND: As sequence data sets used for the investigation of pathogen transmission patterns increase in size, automated tools and standardized methods for cluster analysis have become necessary. We have developed an automated Cluster Picker which identifies monophyletic clades meeting user-input criteria for bootstrap support and maximum genetic distance within large phylogenetic trees. A second tool, the Cluster Matcher, automates the process of linking genetic data to epidemiological or clinical data, and matches clusters between runs of the Cluster Picker. RESULTS: We explore the effect of different bootstrap and genetic distance thresholds on clusters identified in a data set of publicly available HIV sequences, and compare these results to those of a previously published tool for cluster identification. To demonstrate their utility, we then use the Cluster Picker and Cluster Matcher together to investigate how clusters in the data set changed over time. We find that clusters containing sequences from more than one UK location at the first time point (multiple origin) were significantly more likely to grow than those representing only a single location. CONCLUSIONS: The Cluster Picker and Cluster Matcher can rapidly process phylogenetic trees containing tens of thousands of sequences. Together these tools will facilitate comparisons of pathogen transmission dynamics between studies and countries.",2013 Nov 6,"['Ragonnet-Cronin, Manon', 'Hodcroft, Emma', 'Hué, Stéphane', 'Fearnhill, Esther', 'Delpech, Valerie', 'Brown, Andrew J Leigh', 'Lycett, Samantha']",BMC Bioinformatics,,,False
84323c90f9a4e2e339105377d6a0769cc2fa0fbc,PMC,Activation of Innate Immune-Response Genes in Little Brown Bats (Myotis lucifugus) Infected with the Fungus Pseudogymnoascus destructans,http://dx.doi.org/10.1371/journal.pone.0112285,PMC4229191,25391018,CC BY,"Recently bats have been associated with the emergence of diseases, both as reservoirs for several new viral diseases in humans and other animals and, in the northern Americas, as hosts for a devastating fungal disease that threatens to drive several bat species to regional extinction. However, despite these catastrophic events little Information is available on bat defences or how they interact with their pathogens. Even less is known about the response of bats to infection during torpor or long-term hibernation. Using tissue samples collected at the termination of an experiment to explore the pathogenesis of White Nose Syndrome in Little Brown Bats, we determined if hibernating bats infected with the fungus Pseudogymnoascus destructans could respond to infection by activating genes responsible for innate immune and stress responses. Lesions due to fungal infection and, in some cases, secondary bacterial infections, were restricted to the skin. However, we were unable to obtain sufficient amounts of RNA from these sites. We therefore examined lungs for response at an epithelial surface not linked to the primary site of infection. We found that bats responded to infection with a significant increase in lungs of transcripts for Cathelicidin (an anti-microbial peptide) as well as the immune modulators tumor necrosis factor alpha and interleukins 10 and 23. In conclusion, hibernating bats can respond to experimental P. destructans infection by activating expression of innate immune response genes.",2014 Nov 12,"['Rapin, Noreen', 'Johns, Kirk', 'Martin, Lauren', 'Warnecke, Lisa', 'Turner, James M.', 'Bollinger, Trent K.', 'Willis, Craig K. R.', 'Voyles, Jamie', 'Misra, Vikram']",PLoS One,,,True
77f34000cd69ab822903562a0004012eeebe7605,PMC,Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virus-induced acute lung injury,http://dx.doi.org/10.1038/srep07027,PMC4229671,25391767,CC BY,"Since March 2013, the emergence of an avian-origin influenza A (H7N9) virus has raised concern in China. Although most infections resulted in respiratory illness, some severe cases resulted in acute respiratory distress syndrome (ARDS), which is a severe form of acute lung injury (ALI) that further contributes to morbidity. To date, no effective drugs that improve the clinical outcome of influenza A (H7N9) virus-infected patients have been identified. Angiotensin-converting enzyme (ACE) and ACE2 are involved in several pathologies such as cardiovascular functions, renal disease, and acute lung injury. In the current study, we report that ACE2 could mediate the severe acute lung injury induced by influenza A (H7N9) virus infection in an experimental mouse model. Moreover, ACE2 deficiency worsened the disease pathogenesis markedly, mainly by targeting the angiotensin II type 1 receptor (AT1). The current findings demonstrate that ACE2 plays a critical role in influenza A (H7N9) virus-induced acute lung injury, and suggest that might be a useful potential therapeutic target for future influenza A (H7N9) outbreaks.",2014 Nov 13,"['Yang, Penghui', 'Gu, Hongjing', 'Zhao, Zhongpeng', 'Wang, Wei', 'Cao, Bin', 'Lai, Chengcai', 'Yang, Xiaolan', 'Zhang, LiangYan', 'Duan, Yueqiang', 'Zhang, Shaogeng', 'Chen, Weiwen', 'Zhen, Wenbo', 'Cai, Maosheng', 'Penninger, Josef M.', 'Jiang, Chengyu', 'Wang, Xiliang']",Sci Rep,,,True
ba3471e86d6880f42f1df67c9a381e83216d1b45,PMC,From sequence to enzyme mechanism using multi-label machine learning,http://dx.doi.org/10.1186/1471-2105-15-150,PMC4229970,24885296,CC BY,"BACKGROUND: In this work we predict enzyme function at the level of chemical mechanism, providing a finer granularity of annotation than traditional Enzyme Commission (EC) classes. Hence we can predict not only whether a putative enzyme in a newly sequenced organism has the potential to perform a certain reaction, but how the reaction is performed, using which cofactors and with susceptibility to which drugs or inhibitors, details with important consequences for drug and enzyme design. Work that predicts enzyme catalytic activity based on 3D protein structure features limits the prediction of mechanism to proteins already having either a solved structure or a close relative suitable for homology modelling. RESULTS: In this study, we evaluate whether sequence identity, InterPro or Catalytic Site Atlas sequence signatures provide enough information for bulk prediction of enzyme mechanism. By splitting MACiE (Mechanism, Annotation and Classification in Enzymes database) mechanism labels to a finer granularity, which includes the role of the protein chain in the overall enzyme complex, the method can predict at 96% accuracy (and 96% micro-averaged precision, 99.9% macro-averaged recall) the MACiE mechanism definitions of 248 proteins available in the MACiE, EzCatDb (Database of Enzyme Catalytic Mechanisms) and SFLD (Structure Function Linkage Database) databases using an off-the-shelf K-Nearest Neighbours multi-label algorithm. CONCLUSION: We find that InterPro signatures are critical for accurate prediction of enzyme mechanism. We also find that incorporating Catalytic Site Atlas attributes does not seem to provide additional accuracy. The software code (ml2db), data and results are available online at http://sourceforge.net/projects/ml2db/ and as supplementary files.",2014 May 19,"['De Ferrari, Luna', 'Mitchell, John BO']",BMC Bioinformatics,,,True
29688d13b2e9b0f1ce17caa2ec6591c9792f50ba,PMC,From sequence to enzyme mechanism using multi-label machine learning,http://dx.doi.org/10.1186/1471-2105-15-150,PMC4229970,24885296,CC BY,"BACKGROUND: In this work we predict enzyme function at the level of chemical mechanism, providing a finer granularity of annotation than traditional Enzyme Commission (EC) classes. Hence we can predict not only whether a putative enzyme in a newly sequenced organism has the potential to perform a certain reaction, but how the reaction is performed, using which cofactors and with susceptibility to which drugs or inhibitors, details with important consequences for drug and enzyme design. Work that predicts enzyme catalytic activity based on 3D protein structure features limits the prediction of mechanism to proteins already having either a solved structure or a close relative suitable for homology modelling. RESULTS: In this study, we evaluate whether sequence identity, InterPro or Catalytic Site Atlas sequence signatures provide enough information for bulk prediction of enzyme mechanism. By splitting MACiE (Mechanism, Annotation and Classification in Enzymes database) mechanism labels to a finer granularity, which includes the role of the protein chain in the overall enzyme complex, the method can predict at 96% accuracy (and 96% micro-averaged precision, 99.9% macro-averaged recall) the MACiE mechanism definitions of 248 proteins available in the MACiE, EzCatDb (Database of Enzyme Catalytic Mechanisms) and SFLD (Structure Function Linkage Database) databases using an off-the-shelf K-Nearest Neighbours multi-label algorithm. CONCLUSION: We find that InterPro signatures are critical for accurate prediction of enzyme mechanism. We also find that incorporating Catalytic Site Atlas attributes does not seem to provide additional accuracy. The software code (ml2db), data and results are available online at http://sourceforge.net/projects/ml2db/ and as supplementary files.",2014 May 19,"['De Ferrari, Luna', 'Mitchell, John BO']",BMC Bioinformatics,,,False
c181d32e2efda26882425f6179dc5549a59a3504,PMC,ADLD: A Novel Graphical Representation of Protein Sequences and Its Application,http://dx.doi.org/10.1155/2014/959753,PMC4230005,25530796,CC BY,"To facilitate the intuitional analysis of protein sequences, a novel graphical representation of protein sequences called ADLD (Alignment Diagonal Line Diagram) is introduced in this paper first, and then a new ADLD based method is proposed and utilized to analyze the similarity/dissimilarity of protein sequences. Comparing with existing methods, our ADLD based method is proved to be effective in the similarity/dissimilarity analysis of protein sequences and have the merits of good intuition, visuality, and simplicity. The examinations of the similarities/dissimilarities for both the 16 different ND5 proteins and the 29 different spike proteins illustrate the utility of our ADLD based approach.",2014 Oct 30,"['Wang, Lei', 'Peng, Hui', 'Zheng, Jinhua']",Comput Math Methods Med,,,True
dc4a3df470bfd502db850deec4219e39f7eadb63,PMC,Immune Responses to Non-Tumor Antigens in the Central Nervous System,http://dx.doi.org/10.3389/fonc.2014.00328,PMC4230036,25431758,CC BY,"The central nervous system (CNS), once viewed as an immune-privileged site protected by the blood–brain barrier (BBB), is now known to be a dynamic immunological environment through which immune cells migrate to prevent and respond to events such as localized infection. During these responses, endogenous glial cells, including astrocytes and microglia, become highly reactive and may secrete inflammatory mediators that regulate BBB permeability and recruit additional circulating immune cells. Here, we discuss the various roles played by astrocytes, microglia, and infiltrating immune cells during host immunity to non-tumor antigens in the CNS, focusing first on bacterial and viral infections, and then turning to responses directed against self-antigens in the setting of CNS autoimmunity.",2014 Nov 13,"['Huber, Amanda K.', 'Duncker, Patrick C.', 'Irani, David N.']",Front Oncol,,,True
58246d246bb1b2288dc58245c475fc314d34cc83,PMC,Role of Oct4 in the early embryo development,http://dx.doi.org/10.1186/2045-9769-3-7,PMC4230828,25408886,CC BY,"Oct4 is a key component of the pluripotency regulatory network, and its reciprocal interaction with Cdx2 has been shown to be a determinant of either the self-renewal of embryonic stem cells (ESCs) or their differentiation into trophoblast. Oct4 of maternal origin is postulated to play critical role in defining totipotency and inducing pluripotency during embryonic development. However, the genetic elimination of maternal Oct4 using a Cre-lox approach in mouse revealed that the establishment of totipotency in maternal Oct4–depleted embryos was not affected, and that these embryos could complete full-term development without any obvious defect. These results indicate that Oct4 is not essential for the initiation of pluripotency, in contrast to its critical role in maintaining pluripotency. This conclusion is further supported by the formation of Oct4-GFP– and Nanog- expressing inner cell masses (ICMs) in embryos with complete inactivation of both maternal and zygotic Oct4 expression and the reprogramming of fibroblasts into fully pluripotent cells by Oct4-deficient oocytes.",2014 Apr 29,"['Wu, Guangming', 'Schöler, Hans R']",Cell Regen (Lond),,,True
5b7e79c51c0788a3bb6e9c3a67e37d2dfedf9541,PMC,"The Global One Health Paradigm: Challenges and Opportunities for Tackling Infectious Diseases at the Human, Animal, and Environment Interface in Low-Resource Settings",http://dx.doi.org/10.1371/journal.pntd.0003257,PMC4230840,25393303,CC BY,"Zoonotic infectious diseases have been an important concern to humankind for more than 10,000 years. Today, approximately 75% of newly emerging infectious diseases (EIDs) are zoonoses that result from various anthropogenic, genetic, ecologic, socioeconomic, and climatic factors. These interrelated driving forces make it difficult to predict and to prevent zoonotic EIDs. Although significant improvements in environmental and medical surveillance, clinical diagnostic methods, and medical practices have been achieved in the recent years, zoonotic EIDs remain a major global concern, and such threats are expanding, especially in less developed regions. The current Ebola epidemic in West Africa is an extreme stark reminder of the role animal reservoirs play in public health and reinforces the urgent need for globally operationalizing a One Health approach. The complex nature of zoonotic diseases and the limited resources in developing countries are a reminder that the need for implementation of Global One Health in low-resource settings is crucial. The Veterinary Public Health and Biotechnology (VPH-Biotec) Global Consortium launched the International Congress on Pathogens at the Human-Animal Interface (ICOPHAI) in order to address important challenges and needs for capacity building. The inaugural ICOPHAI (Addis Ababa, Ethiopia, 2011) and the second congress (Porto de Galinhas, Brazil, 2013) were unique opportunities to share and discuss issues related to zoonotic infectious diseases worldwide. In addition to strong scientific reports in eight thematic areas that necessitate One Health implementation, the congress identified four key capacity-building needs: (1) development of adequate science-based risk management policies, (2) skilled-personnel capacity building, (3) accredited veterinary and public health diagnostic laboratories with a shared database, and (4) improved use of existing natural resources and implementation. The aim of this review is to highlight advances in key zoonotic disease areas and the One Health capacity needs.",2014 Nov 13,"['Gebreyes, Wondwossen A.', 'Dupouy-Camet, Jean', 'Newport, Melanie J.', 'Oliveira, Celso J. B.', 'Schlesinger, Larry S.', 'Saif, Yehia M.', 'Kariuki, Samuel', 'Saif, Linda J.', 'Saville, William', 'Wittum, Thomas', 'Hoet, Armando', 'Quessy, Sylvain', 'Kazwala, Rudovick', 'Tekola, Berhe', 'Shryock, Thomas', 'Bisesi, Michael', 'Patchanee, Prapas', 'Boonmar, Sumalee', 'King, Lonnie J.']",PLoS Negl Trop Dis,,,True
b3d980d9df2556687fc5d6bf3b18c95215da600c,PMC,Atomistic Detailed Mechanism and Weak Cation-Conducting Activity of HIV-1 Vpu Revealed by Free Energy Calculations,http://dx.doi.org/10.1371/journal.pone.0112983,PMC4231112,25392993,CC BY,"The viral protein U (Vpu) encoded by HIV-1 has been shown to assist in the detachment of virion particles from infected cells. Vpu forms cation-specific ion channels in host cells, and has been proposed as a potential drug target. An understanding of the mechanism of ion transport through Vpu is desirable, but remains limited because of the unavailability of an experimental structure of the channel. Using a structure of the pentameric form of Vpu – modeled and validated based on available experimental data – umbrella sampling molecular dynamics simulations (cumulative simulation time of more than 0.4 µs) were employed to elucidate the energetics and the molecular mechanism of ion transport in Vpu. Free energy profiles corresponding to the permeation of Na(+) and K(+) were found to be similar to each other indicating lack of ion selection, consistent with previous experimental studies. The Ser23 residue is shown to enhance ion transport via two mechanisms: creating a weak binding site, and increasing the effective hydrophilic length of the channel, both of which have previously been hypothesized in experiments. A two-dimensional free energy landscape has been computed to model multiple ion permeation, based on which a mechanism for ion conduction is proposed. It is shown that only one ion can pass through the channel at a time. This, along with a stretch of hydrophobic residues in the transmembrane domain of Vpu, explains the slow kinetics of ion conduction. The results are consistent with previous conductance studies that showed Vpu to be a weakly conducting ion channel.",2014 Nov 13,"['Padhi, Siladitya', 'Burri, Raghunadha Reddy', 'Jameel, Shahid', 'Priyakumar, U. Deva']",PLoS One,,,True
991fb0c5b5cd686d096e2b05d8dc19ca22213df4,PMC,Induction of robust immunity response in mice by dual-expression-system-based recombinant baculovirus expressing the capsid protein of porcine circovirus type 2,http://dx.doi.org/10.1186/1743-422X-10-316,PMC4231451,24161107,CC BY,"BACKGROUND: Porcine circovirus type 2 (PCV2) is associated with post-weaning multisystemic wasting syndrome (PMWS), an emerging swine disease that causes progressive weight loss, dyspnea, tachypnea, anemia, jaundice, and diarrhea in piglets. Although baculovirus is an enveloped virus that infects insects in nature, it has emerged as a vaccine vector, and we used it to develop a novel candidate vaccine for a preventive or therapeutic strategy to control PCV2 infections. METHODS: Immunoblotting analysis of recombinant baculovirus and immunofluorescent staining of baculovirus-infected cells were followed using anti-ORF2 monoclonal antibodies. The BALB/c mice were immunized intramuscularly with this baculovirus. The titers of antibodies were mensurated with a Cap-protein-specific enzyme-linked immunosorbent assay (ELISA) and a serum neutralization assay. The IFN-γ response in splenocytes harvested from immunized mice was measured by ELISA. Student's t-test was used to compare immune responses of different groups. RESULTS: In this study, we successfully constructed a dual-expression-system-based recombinant baculovirus BV-GD-ORF2, which can display the PCV2 capsid (Cap) protein and VSV-G protein on the viral envelope and also expressing Cap protein on transduced mammalian cells, thereby functioning as both a subunit and a DNA vaccine. After infection, the Cap protein was expressed and displayed on the viral surface, as demonstrated with an indirect fluorescence assay and immunoblotting. The vaccination of mice with recombinant baculovirus BV-GD-ORF2 successfully induced robust Cap-protein-specific humoral and cellular immune responses. CONCLUSIONS: Our findings collectively demonstrate that the recombinant baculovirus BV-GD-ORF2 is a potential vaccine against PCV2 infections.",2013 Oct 28,"['Ye, Yu', 'Cheng, Xiaoliang', 'Zhang, Jie', 'Tong, Tiezhu', 'Lin, Wenyao', 'Liao, Ming', 'Fan, Huiying']",Virol J,,,True
f11b19a9e1845ff5ab66a42d5409f8caed24faa1,PMC,"Sequencing, Annotation and Analysis of the Syrian Hamster (Mesocricetus auratus) Transcriptome",http://dx.doi.org/10.1371/journal.pone.0112617,PMC4232415,25398096,CC0,"BACKGROUND: The Syrian hamster (golden hamster, Mesocricetus auratus) is gaining importance as a new experimental animal model for multiple pathogens, including emerging zoonotic diseases such as Ebola. Nevertheless there are currently no publicly available transcriptome reference sequences or genome for this species. RESULTS: A cDNA library derived from mRNA and snRNA isolated and pooled from the brains, lungs, spleens, kidneys, livers, and hearts of three adult female Syrian hamsters was sequenced. Sequence reads were assembled into 62,482 contigs and 111,796 reads remained unassembled (singletons). This combined contig/singleton dataset, designated as the Syrian hamster transcriptome, represents a total of 60,117,204 nucleotides. Our Mesocricetus auratus Syrian hamster transcriptome mapped to 11,648 mouse transcripts representing 9,562 distinct genes, and mapped to a similar number of transcripts and genes in the rat. We identified 214 quasi-complete transcripts based on mouse annotations. Canonical pathways involved in a broad spectrum of fundamental biological processes were significantly represented in the library. The Syrian hamster transcriptome was aligned to the current release of the Chinese hamster ovary (CHO) cell transcriptome and genome to improve the genomic annotation of this species. Finally, our Syrian hamster transcriptome was aligned against 14 other rodents, primate and laurasiatheria species to gain insights about the genetic relatedness and placement of this species. CONCLUSIONS: This Syrian hamster transcriptome dataset significantly improves our knowledge of the Syrian hamster's transcriptome, especially towards its future use in infectious disease research. Moreover, this library is an important resource for the wider scientific community to help improve genome annotation of the Syrian hamster and other closely related species. Furthermore, these data provide the basis for development of expression microarrays that can be used in functional genomics studies.",2014 Nov 14,"['Tchitchek, Nicolas', 'Safronetz, David', 'Rasmussen, Angela L.', 'Martens, Craig', 'Virtaneva, Kimmo', 'Porcella, Stephen F.', 'Feldmann, Heinz', 'Ebihara, Hideki', 'Katze, Michael G.']",PLoS One,,,True
1248f79908add5049ea87ca9c44b851d841d5b54,PMC,"Sequencing, Annotation and Analysis of the Syrian Hamster (Mesocricetus auratus) Transcriptome",http://dx.doi.org/10.1371/journal.pone.0112617,PMC4232415,25398096,CC0,"BACKGROUND: The Syrian hamster (golden hamster, Mesocricetus auratus) is gaining importance as a new experimental animal model for multiple pathogens, including emerging zoonotic diseases such as Ebola. Nevertheless there are currently no publicly available transcriptome reference sequences or genome for this species. RESULTS: A cDNA library derived from mRNA and snRNA isolated and pooled from the brains, lungs, spleens, kidneys, livers, and hearts of three adult female Syrian hamsters was sequenced. Sequence reads were assembled into 62,482 contigs and 111,796 reads remained unassembled (singletons). This combined contig/singleton dataset, designated as the Syrian hamster transcriptome, represents a total of 60,117,204 nucleotides. Our Mesocricetus auratus Syrian hamster transcriptome mapped to 11,648 mouse transcripts representing 9,562 distinct genes, and mapped to a similar number of transcripts and genes in the rat. We identified 214 quasi-complete transcripts based on mouse annotations. Canonical pathways involved in a broad spectrum of fundamental biological processes were significantly represented in the library. The Syrian hamster transcriptome was aligned to the current release of the Chinese hamster ovary (CHO) cell transcriptome and genome to improve the genomic annotation of this species. Finally, our Syrian hamster transcriptome was aligned against 14 other rodents, primate and laurasiatheria species to gain insights about the genetic relatedness and placement of this species. CONCLUSIONS: This Syrian hamster transcriptome dataset significantly improves our knowledge of the Syrian hamster's transcriptome, especially towards its future use in infectious disease research. Moreover, this library is an important resource for the wider scientific community to help improve genome annotation of the Syrian hamster and other closely related species. Furthermore, these data provide the basis for development of expression microarrays that can be used in functional genomics studies.",2014 Nov 14,"['Tchitchek, Nicolas', 'Safronetz, David', 'Rasmussen, Angela L.', 'Martens, Craig', 'Virtaneva, Kimmo', 'Porcella, Stephen F.', 'Feldmann, Heinz', 'Ebihara, Hideki', 'Katze, Michael G.']",PLoS One,,,False
cc653d610df635aab4288b596359b83a38eb123b,PMC,"Sequencing, Annotation and Analysis of the Syrian Hamster (Mesocricetus auratus) Transcriptome",http://dx.doi.org/10.1371/journal.pone.0112617,PMC4232415,25398096,CC0,"BACKGROUND: The Syrian hamster (golden hamster, Mesocricetus auratus) is gaining importance as a new experimental animal model for multiple pathogens, including emerging zoonotic diseases such as Ebola. Nevertheless there are currently no publicly available transcriptome reference sequences or genome for this species. RESULTS: A cDNA library derived from mRNA and snRNA isolated and pooled from the brains, lungs, spleens, kidneys, livers, and hearts of three adult female Syrian hamsters was sequenced. Sequence reads were assembled into 62,482 contigs and 111,796 reads remained unassembled (singletons). This combined contig/singleton dataset, designated as the Syrian hamster transcriptome, represents a total of 60,117,204 nucleotides. Our Mesocricetus auratus Syrian hamster transcriptome mapped to 11,648 mouse transcripts representing 9,562 distinct genes, and mapped to a similar number of transcripts and genes in the rat. We identified 214 quasi-complete transcripts based on mouse annotations. Canonical pathways involved in a broad spectrum of fundamental biological processes were significantly represented in the library. The Syrian hamster transcriptome was aligned to the current release of the Chinese hamster ovary (CHO) cell transcriptome and genome to improve the genomic annotation of this species. Finally, our Syrian hamster transcriptome was aligned against 14 other rodents, primate and laurasiatheria species to gain insights about the genetic relatedness and placement of this species. CONCLUSIONS: This Syrian hamster transcriptome dataset significantly improves our knowledge of the Syrian hamster's transcriptome, especially towards its future use in infectious disease research. Moreover, this library is an important resource for the wider scientific community to help improve genome annotation of the Syrian hamster and other closely related species. Furthermore, these data provide the basis for development of expression microarrays that can be used in functional genomics studies.",2014 Nov 14,"['Tchitchek, Nicolas', 'Safronetz, David', 'Rasmussen, Angela L.', 'Martens, Craig', 'Virtaneva, Kimmo', 'Porcella, Stephen F.', 'Feldmann, Heinz', 'Ebihara, Hideki', 'Katze, Michael G.']",PLoS One,,,False
9650f6d8d76fe3f5624405c98b967b6b6a424e01,PMC,"Sequencing, Annotation and Analysis of the Syrian Hamster (Mesocricetus auratus) Transcriptome",http://dx.doi.org/10.1371/journal.pone.0112617,PMC4232415,25398096,CC0,"BACKGROUND: The Syrian hamster (golden hamster, Mesocricetus auratus) is gaining importance as a new experimental animal model for multiple pathogens, including emerging zoonotic diseases such as Ebola. Nevertheless there are currently no publicly available transcriptome reference sequences or genome for this species. RESULTS: A cDNA library derived from mRNA and snRNA isolated and pooled from the brains, lungs, spleens, kidneys, livers, and hearts of three adult female Syrian hamsters was sequenced. Sequence reads were assembled into 62,482 contigs and 111,796 reads remained unassembled (singletons). This combined contig/singleton dataset, designated as the Syrian hamster transcriptome, represents a total of 60,117,204 nucleotides. Our Mesocricetus auratus Syrian hamster transcriptome mapped to 11,648 mouse transcripts representing 9,562 distinct genes, and mapped to a similar number of transcripts and genes in the rat. We identified 214 quasi-complete transcripts based on mouse annotations. Canonical pathways involved in a broad spectrum of fundamental biological processes were significantly represented in the library. The Syrian hamster transcriptome was aligned to the current release of the Chinese hamster ovary (CHO) cell transcriptome and genome to improve the genomic annotation of this species. Finally, our Syrian hamster transcriptome was aligned against 14 other rodents, primate and laurasiatheria species to gain insights about the genetic relatedness and placement of this species. CONCLUSIONS: This Syrian hamster transcriptome dataset significantly improves our knowledge of the Syrian hamster's transcriptome, especially towards its future use in infectious disease research. Moreover, this library is an important resource for the wider scientific community to help improve genome annotation of the Syrian hamster and other closely related species. Furthermore, these data provide the basis for development of expression microarrays that can be used in functional genomics studies.",2014 Nov 14,"['Tchitchek, Nicolas', 'Safronetz, David', 'Rasmussen, Angela L.', 'Martens, Craig', 'Virtaneva, Kimmo', 'Porcella, Stephen F.', 'Feldmann, Heinz', 'Ebihara, Hideki', 'Katze, Michael G.']",PLoS One,,,False
21b5f4d12c8a8f488141e25fd334b4cc6e6270d2,PMC,"Sequencing, Annotation and Analysis of the Syrian Hamster (Mesocricetus auratus) Transcriptome",http://dx.doi.org/10.1371/journal.pone.0112617,PMC4232415,25398096,CC0,"BACKGROUND: The Syrian hamster (golden hamster, Mesocricetus auratus) is gaining importance as a new experimental animal model for multiple pathogens, including emerging zoonotic diseases such as Ebola. Nevertheless there are currently no publicly available transcriptome reference sequences or genome for this species. RESULTS: A cDNA library derived from mRNA and snRNA isolated and pooled from the brains, lungs, spleens, kidneys, livers, and hearts of three adult female Syrian hamsters was sequenced. Sequence reads were assembled into 62,482 contigs and 111,796 reads remained unassembled (singletons). This combined contig/singleton dataset, designated as the Syrian hamster transcriptome, represents a total of 60,117,204 nucleotides. Our Mesocricetus auratus Syrian hamster transcriptome mapped to 11,648 mouse transcripts representing 9,562 distinct genes, and mapped to a similar number of transcripts and genes in the rat. We identified 214 quasi-complete transcripts based on mouse annotations. Canonical pathways involved in a broad spectrum of fundamental biological processes were significantly represented in the library. The Syrian hamster transcriptome was aligned to the current release of the Chinese hamster ovary (CHO) cell transcriptome and genome to improve the genomic annotation of this species. Finally, our Syrian hamster transcriptome was aligned against 14 other rodents, primate and laurasiatheria species to gain insights about the genetic relatedness and placement of this species. CONCLUSIONS: This Syrian hamster transcriptome dataset significantly improves our knowledge of the Syrian hamster's transcriptome, especially towards its future use in infectious disease research. Moreover, this library is an important resource for the wider scientific community to help improve genome annotation of the Syrian hamster and other closely related species. Furthermore, these data provide the basis for development of expression microarrays that can be used in functional genomics studies.",2014 Nov 14,"['Tchitchek, Nicolas', 'Safronetz, David', 'Rasmussen, Angela L.', 'Martens, Craig', 'Virtaneva, Kimmo', 'Porcella, Stephen F.', 'Feldmann, Heinz', 'Ebihara, Hideki', 'Katze, Michael G.']",PLoS One,,,False
4ed270652370f2ffd9aecd7288519c77d7b925ea,PMC,Hijacking of an autophagy-like process is critical for the life cycle of a DNA virus infecting oceanic algal blooms,http://dx.doi.org/10.1111/nph.13008,PMC4233938,25195618,CC BY,"Marine photosynthetic microorganisms are the basis of marine food webs and are responsible for nearly 50% of the global primary production. Emiliania huxleyi forms massive oceanic blooms that are routinely terminated by large double-stranded DNA coccolithoviruses. The cellular mechanisms that govern the replication cycle of these giant viruses are largely unknown. We used diverse techniques, including fluorescence microscopy, transmission electron microscopy, cryoelectron tomography, immunolabeling and biochemical methodologies to investigate the role of autophagy in host–virus interactions. Hallmarks of autophagy are induced during the lytic phase of E. huxleyi viral infection, concomitant with up-regulation of autophagy-related genes (ATG genes). Pretreatment of the infected cells with an autophagy inhibitor causes a major reduction in the production of extracellular viral particles, without reducing viral DNA replication within the cell. The host-encoded Atg8 protein was detected within purified virions, demonstrating the pivotal role of the autophagy-like process in viral assembly and egress. We show that autophagy, which is classically considered as a defense mechanism, is essential for viral propagation and for facilitating a high burst size. This cellular mechanism may have a major impact on the fate of the viral-infected blooms, and therefore on the cycling of nutrients within the marine ecosystem.",2014 Dec 7,"['Schatz, Daniella', 'Shemi, Adva', 'Rosenwasser, Shilo', 'Sabanay, Helena', 'Wolf, Sharon G', 'Ben-Dor, Shifra', 'Vardi, Assaf']",New Phytol,,,True
7ac54db3298b52d9d78f4255e40447904bd90ad7,PMC,Enterovirus 71 Induces Mitochondrial Reactive Oxygen Species Generation That is Required for Efficient Replication,http://dx.doi.org/10.1371/journal.pone.0113234,PMC4234665,25401329,CC BY,"Redox homeostasis is an important host factor determining the outcome of infectious disease. Enterovirus 71 (EV71) infection has become an important endemic disease in Southeast Asia and China. We have previously shown that oxidative stress promotes viral replication, and progeny virus induces oxidative stress in host cells. The detailed mechanism for reactive oxygen species (ROS) generation in infected cells remains elusive. In the current study, we demonstrate that mitochondria were a major ROS source in EV71-infected cells. Mitochondria in productively infected cells underwent morphologic changes and exhibited functional anomalies, such as a decrease in mitochondrial electrochemical potential ΔΨ(m) and an increase in oligomycin-insensitive oxygen consumption. Respiratory control ratio of mitochondria from infected cells was significantly lower than that of normal cells. The total adenine nucleotide pool and ATP content of EV71-infected cells significantly diminished. However, there appeared to be a compensatory increase in mitochondrial mass. Treatment with mito-TEMPO reduced eIF2α phosphorylation and viral replication, suggesting that mitochondrial ROS act to promote viral replication. It is plausible that EV71 infection induces mitochondrial ROS generation, which is essential to viral replication, at the sacrifice of efficient energy production, and that infected cells up-regulate biogenesis of mitochondria to compensate for their functional defect.",2014 Nov 17,"['Cheng, Mei-Ling', 'Weng, Shiue-Fen', 'Kuo, Chih-Hao', 'Ho, Hung-Yao']",PLoS One,,,True
f04ae49e396269b6fc64538613ea9a6d53583bd6,PMC,Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley Fever vaccine in mice,http://dx.doi.org/10.1186/1743-422X-10-349,PMC4235025,24304565,CC BY,"BACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. METHODS: Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. RESULTS: A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8(+) T cell response. CONCLUSIONS: Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.",2013 Dec 5,"['Warimwe, George M', 'Lorenzo, Gema', 'Lopez-Gil, Elena', 'Reyes-Sandoval, Arturo', 'Cottingham, Matthew G', 'Spencer, Alexandra J', 'Collins, Katharine A', 'Dicks, Matthew DJ', 'Milicic, Anita', 'Lall, Amar', 'Furze, Julie', 'Turner, Alison V', 'Hill, Adrian VS', 'Brun, Alejandro', 'Gilbert, Sarah C']",Virol J,,,True
ffd791c34aa1431d8571663c1fa722086d0ad90f,PMC,Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley Fever vaccine in mice,http://dx.doi.org/10.1186/1743-422X-10-349,PMC4235025,24304565,CC BY,"BACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. METHODS: Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. RESULTS: A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8(+) T cell response. CONCLUSIONS: Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.",2013 Dec 5,"['Warimwe, George M', 'Lorenzo, Gema', 'Lopez-Gil, Elena', 'Reyes-Sandoval, Arturo', 'Cottingham, Matthew G', 'Spencer, Alexandra J', 'Collins, Katharine A', 'Dicks, Matthew DJ', 'Milicic, Anita', 'Lall, Amar', 'Furze, Julie', 'Turner, Alison V', 'Hill, Adrian VS', 'Brun, Alejandro', 'Gilbert, Sarah C']",Virol J,,,True
05e4c2f6b0affdeef1b7d99d5b481bee1c244a7f,PMC,Human Bocavirus: Lessons Learned to Date,http://dx.doi.org/10.3390/pathogens2010001,PMC4235705,25436878,CC BY,"Human bocavirus (HBoV) was identified as the second human parvovirus with pathogenic potential in 2005 in respiratory samples from children suffering from viral respiratory infections of unknown etiology. Since its first description, a large number of clinical studies have been performed that address the clinical significance of HBoV detection and the molecular biology of the virus. This review summarizes the most important steps taken in HBoV research to date and addresses open questions that need to be answered in the future to provide a better understanding of the role of a virus that is difficult to grow in cell culture and is suspected to be a pathogen, although it has not yet fulfilled Koch’s postulates.",2013 Jan 11,"Schildgen, Oliver",Pathogens,,,True
4be32977ea29039cf2fac3b4327ceea8f14d0af4,PMC,Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases,http://dx.doi.org/10.3390/pathogens2010153,PMC4235711,25436886,CC BY,"Epstein-Barr virus (EBV) is a ubiquitous herpesvirus infecting more than 90% of the adult population of the world. EBV is associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma, and autoimmune diseases including rheumatoid arthritis (RA). EBV in nature infects only humans, but in an experimental setting, a limited species of new-world monkeys can be infected with the virus. Small animal models, suitable for evaluation of novel therapeutics and vaccines, have not been available. Humanized mice, defined here as mice harboring functioning human immune system components, are easily infected with EBV that targets cells of the hematoimmune system. Furthermore, humanized mice can mount both cellular and humoral immune responses to EBV. Thus, many aspects of human EBV infection, including associated diseases (e.g., lymphoproliferative disease, hemophagocytic lymphohistiocytosis and erosive arthritis resembling RA), latent infection, and T-cell-mediated and humoral immune responses have been successfully reproduced in humanized mice. Here we summarize recent achievements in the field of humanized mouse models of EBV infection and show how they have been utilized to analyze EBV pathogenesis and normal and aberrant human immune responses to the virus.",2013 Mar 14,"['Fujiwara, Shigeyoshi', 'Matsuda, Go', 'Imadome, Ken-Ichi']",Pathogens,,,True
c9e24b269c1f1772454a1e93cc72c85251aeda6b,PMC,Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen,http://dx.doi.org/10.1371/journal.pone.0112602,PMC4236105,25405618,CC BY,"The development of an effective vaccine is critical for prevention of a Middle East respiratory syndrome coronavirus (MERS-CoV) pandemic. Some studies have indicated the receptor-binding domain (RBD) protein of MERS-CoV spike (S) is a good candidate antigen for a MERS-CoV subunit vaccine. However, highly purified proteins are typically not inherently immunogenic. We hypothesised that humoral and cell-mediated immunity would be improved with a modification of the vaccination regimen. Therefore, the immunogenicity of a novel MERS-CoV RBD-based subunit vaccine was tested in mice using different adjuvant formulations and delivery routes. Different vaccination regimens were compared in BALB/c mice immunized 3 times intramuscularly (i.m.) with a vaccine containing 10 µg of recombinant MERS-CoV RBD in combination with either aluminium hydroxide (alum) alone, alum and polyriboinosinic acid (poly I:C) or alum and cysteine-phosphate-guanine (CpG) oligodeoxynucleotides (ODN). The immune responses of mice vaccinated with RBD, incomplete Freund’s adjuvant (IFA) and CpG ODN by a subcutaneous (s.c.) route were also investigated. We evaluated the induction of RBD-specific humoral immunity (total IgG and neutralizing antibodies) and cellular immunity (ELISpot assay for IFN-γ spot-forming cells and splenocyte cytokine production). Our findings indicated that the combination of alum and CpG ODN optimized the development of RBD-specific humoral and cellular immunity following subunit vaccination. Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. Our data suggest that murine immunity following subunit vaccination can be tailored using adjuvant combinations and delivery routes. The vaccination regimen used in this study is promising and could improve the protection offered by the MERS-CoV subunit vaccine by eliciting effective humoral and cellular immune responses.",2014 Nov 18,"['Lan, Jiaming', 'Deng, Yao', 'Chen, Hong', 'Lu, Guangwen', 'Wang, Wen', 'Guo, Xiaojuan', 'Lu, Zhuozhuang', 'Gao, George F.', 'Tan, Wenjie']",PLoS One,,,True
085c71736d6b79717bb03aec375310d9e536f851,PMC,PTB Binds to the 3’ Untranslated Region of the Human Astrovirus Type 8: A Possible Role in Viral Replication,http://dx.doi.org/10.1371/journal.pone.0113113,PMC4236132,25406089,CC BY,"The 3′ untranslated region (3′UTR) of human astroviruses (HAstV) consists of two hairpin structures (helix I and II) joined by a linker harboring a conserved PTB/hnRNP1 binding site. The identification and characterization of cellular proteins that interact with the 3′UTR of HAstV-8 virus will help to uncover cellular requirements for viral functions. To this end, mobility shift assays and UV cross-linking were performed with uninfected and HAstV-8-infected cell extracts and HAstV-8 3′UTR probes. Two RNA-protein complexes (CI and CII) were recruited into the 3′UTR. Complex CII formation was compromised with cold homologous RNA, and seven proteins of 35, 40, 45, 50, 52, 57/60 and 75 kDa were cross-linked to the 3′UTR. Supermobility shift assays indicated that PTB/hnRNP1 is part of this complex, and 3′UTR-crosslinked PTB/hnRNP1 was immunoprecipitated from HAstV-8 infected cell-membrane extracts. Also, immunofluorescence analyses revealed that PTB/hnRNP1 is distributed in the nucleus and cytoplasm of uninfected cells, but it is mainly localized perinuclearly in the cytoplasm of HAstV-8 infected cells. Furthermore, the minimal 3′UTR sequences recognized by recombinant PTB are those conforming helix I, and an intact PTB/hnRNP1-binding site. Finally, small interfering RNA-mediated PTB/hnRNP1 silencing reduced synthesis viral genome and virus yield in CaCo2 cells, suggesting that PTB/hnRNP1 is required for HAstV replication. In conclusion, PTB/hnRNP1 binds to the 3′UTR HAstV-8 and is required or participates in viral replication.",2014 Nov 18,"['Espinosa-Hernández, Wendy', 'Velez-Uriza, Dora', 'Valdés, Jesús', 'Vélez-Del Valle, Cristina', 'Salas-Benito, Juan', 'Martínez-Contreras, Rebeca', 'García-Espítia, Matilde', 'Salas-Benito, Mariana', 'Vega-Almeida, Tania', 'De Nova-Ocampo, Mónica']",PLoS One,,,True
60498316646f729173d57cac8d9c2cf9a701a2c9,PMC,Profiling bacterial community in upper respiratory tracts,http://dx.doi.org/10.1186/s12879-014-0583-3,PMC4236460,25391813,CC BY,"BACKGROUND: Infection by pathogenic viruses results in rapid epithelial damage and significantly impacts on the condition of the upper respiratory tract, thus the effects of viral infection may induce changes in microbiota. Thus, we aimed to define the healthy microbiota and the viral pathogen-affected microbiota in the upper respiratory tract. In addition, any association between the type of viral agent and the resultant microbiota profile was assessed. METHODS: We analyzed the upper respiratory tract bacterial content of 57 healthy asymptomatic people (17 health-care workers and 40 community people) and 59 patients acutely infected with influenza, parainfluenza, rhino, respiratory syncytial, corona, adeno, or metapneumo viruses using culture-independent pyrosequencing. RESULTS: The healthy subjects harbored primarily Streptococcus, whereas the patients showed an enrichment of Haemophilus or Moraxella. Quantifying the similarities between bacterial populations by using Fast UniFrac analysis indicated that bacterial profiles were apparently divisible into 6 oropharyngeal types in the tested subjects. The oropharyngeal types were not associated with the type of viruses, but were rather linked to the age of the subjects. Moraxella nonliquefaciens exhibited unprecedentedly high abundance in young subjects aged <6 years. The genome of M. nonliquefaciens was found to encode various proteins that may play roles in pathogenesis. CONCLUSIONS: This study identified 6 oropharyngeal microbiome types. No virus-specific bacterial profile was discovered, but comparative analysis of healthy adults and patients identified a bacterium specific to young patients, M. nonliquefaciens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0583-3) contains supplementary material, which is available to authorized users.",2014 Nov 13,"['Yi, Hana', 'Yong, Dongeun', 'Lee, Kyungwon', 'Cho, Yong-Joon', 'Chun, Jongsik']",BMC Infect Dis,,,True
408fb49191d282aa03d722d951eb500a1dde3b87,PMC,Carrageenan nasal spray in virus confirmed common cold: individual patient data analysis of two randomized controlled trials,http://dx.doi.org/10.1186/2049-6958-9-57,PMC4236476,25411637,CC BY,"BACKGROUND: Clinical trials applying iota-carrageenan nasal spray have previously shown to reduce duration of virus-confirmed common cold. The present study pooled data of two similar clinical trials to provide further evidence for the antiviral effectiveness of carrageenan. METHODS: Individual patient data were analyzed from two randomized double blind placebo controlled trials assessing the therapeutic effectiveness of carrageenan nasal spray in acute common cold. Patients with virus-confirmed common cold (n = 254, verum 126, placebo 128) were included and the following parameters were appraised: duration of disease, number of patients with relapses, number of respiratory viruses and viral titers at inclusion (visit 1) compared to days 3–5 (visit 2). RESULTS: Carrageenan treated patients showed a significant reduction in duration of disease of almost 2 days (p < 0.05) as well as significantly fewer relapses during 21 days of observation period (p < 0.05). The virus clearance between visit 1 and visit 2 was significantly more pronounced in the carrageenan group (p < 0.05). In both studies, virus-confirmed common cold was caused by three main virus subtypes: human rhinovirus (46%), human coronavirus (25%) and influenza A (14%) virus. Carrageenan nasal spray showed significant antiviral efficacy in all three virus subgroups, the highest effectiveness was observed in human corona virus-infected patients. The reduced duration of disease was 3 days (p < 0.01) and the number of relapses was three times less (p < 0.01) in carrageenan treated corona-virus-infected patients compared to control patients. CONCLUSIONS: Administration of carrageenan nasal spray in children as well as in adults suffering from virus-confirmed common cold reduced duration of disease, increased viral clearance and reduced relapses of symptoms. Carrageenan nasal spray appeared as an effective treatment of common cold in children and adults. TRIAL REGISTRATION: Pooled data from ISRCTN52519535 and ISRCTN80148028",2014 Nov 12,"['Koenighofer, Martin', 'Lion, Thomas', 'Bodenteich, Angelika', 'Prieschl-Grassauer, Eva', 'Grassauer, Andreas', 'Unger, Hermann', 'Mueller, Christian A', 'Fazekas, Tamás']",Multidiscip Respir Med,,,True
2934008a223a07e3fd3c886db120eb1fe3aab567,PMC,Respiratory virus is a real pathogen in immunocompetent community-acquired pneumonia: comparing to influenza like illness and volunteer controls,http://dx.doi.org/10.1186/1471-2466-14-144,PMC4236731,25178477,CC BY,"BACKGROUND: Viral pathogens were more commonly reported than previously estimated in community-acquired pneumonia (CAP) patients. However, the real role of virus was still controversial. METHODS: Consecutive adult patients with CAP between April and December, 2009 were prospectively enrolled. A four-fold or greater increase of IgG-titres against respiratory viruses in pair sera was tested by means of hemagglutination inhibition assay or indirect immunofluorescence. Swab samples were tested by cell culture and/or nucleic amplification tests. Viral etiology was considered definitive if at least one of the above tests was positive. RESULTS: Viral etiology was established in fifty-two (34.9%) of 149 CAP patients, twenty-two (81.5%) of 27 influenza like illness patients, and none of 75 volunteer controls. Forty-seven CAP patients were infected by a single virus (24 influenza A virus, 5 influenza B, 10 parainfluenza virus type 3 [PIV-3], 2 PIV-1, 2 adenovirus, 2 human rhinovirus and 2 coronavirus OC43), five cases by two or three viruses co-infection. Fever ≥ 39°C (66.7%), fatigue (64.6%), and purulent sputum (52.1%) was the most common symptoms in viral pneumonia patients. On multivariate analysis, myalgia was included in the model for pneumonia associated with influenza infection. In the CURB-65 model only influenza infection was found independently associated with severe disease (CURB-65 score ≥ 3) out of variables, including age(years), sex, current smoking status, sick contact with febrile patients, numbers of comorbidity, presence of influenza infection, presence of PIV infection, with P = 0.021, OR 7.86 (95% CI 1.37-45.04). CONCLUSION: Respiratory virus was not a bystander, but pathogenic in pneumonia and was a common cause of CAP.",2014 Sep 2,"['Zhan, Yangqing', 'Yang, Zifeng', 'Chen, Rongchang', 'Wang, Yutao', 'Guan, Wenda', 'Zhao, Suishan']",BMC Pulm Med,,,True
94c6aacd8aeb83b9798d43627bcf867944fb8afd,PMC,An eight-year epidemiologic study based on baculovirus-expressed type-specific spike proteins for the differentiation of type I and II feline coronavirus infections,http://dx.doi.org/10.1186/s12917-014-0186-7,PMC4236817,25123112,CC BY,"BACKGROUND: Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus (FCoV). FCoVs are divided into two serotypes with markedly different infection rates among cat populations around the world. A baculovirus-expressed type-specific domain of the spike proteins of FCoV was used to survey the infection of the two viruses over the past eight years in Taiwan. RESULTS: An immunofluorescence assay based on cells infected with the recombinant viruses that was capable of distinguishing between the two types of viral infection was established. A total of 833 cases from a teaching hospital was surveyed for prevalence of different FCoV infections. Infection of the type I FCoV was dominant, with a seropositive rate of 70.4%, whereas 3.5% of cats were infected with the type II FCoV. In most cases, results derived from serotyping and genotyping were highly agreeable. However, 16.7% (4/24) FIP cats and 9.8% (6/61) clinically healthy cats were found to possess antibodies against both viruses. Moreover, most of the cats (84.6%, 22/26) infected with a genotypic untypable virus bearing a type I FCoV antibody. CONCLUSION: A relatively simple serotyping method to distinguish between two types of FCoV infection was developed. Based on this method, two types of FCoV infection in Taiwan was first carried out. Type I FCoV was found to be predominant compared with type II virus. Results derived from serotyping and genotyping support our current understanding of evolution of disease-related FCoV and transmission of FIP.",2014 Aug 15,"['Wang, Ying-Ting', 'Chueh, Ling-Ling', 'Wan, Cho-Hua']",BMC Vet Res,,,True
d7a80f6f56131be32a661d7604b38c6a893ded50,PMC,CD26/DPP4 Cell-Surface Expression in Bat Cells Correlates with Bat Cell Susceptibility to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Evolution of Persistent Infection,http://dx.doi.org/10.1371/journal.pone.0112060,PMC4237331,25409519,CC0,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors.",2014 Nov 19,"['Caì, Yíngyún', 'Yú, Shuǐqìng', 'Postnikova, Elena N.', 'Mazur, Steven', 'Bernbaum, John G.', 'Burk, Robin', 'Zhāng, Téngfēi', 'Radoshitzky, Sheli R.', 'Müller, Marcel A.', 'Jordan, Ingo', 'Bollinger, Laura', 'Hensley, Lisa E.', 'Jahrling, Peter B.', 'Kuhn, Jens H.']",PLoS One,,,True
f87c8bfc787731a80acd6bf082c748c41afb8a4a,PMC,Frequency and Fitness Consequences of Bacteriophage Φ6 Host Range Mutations,http://dx.doi.org/10.1371/journal.pone.0113078,PMC4237377,25409341,CC BY,"Viruses readily mutate and gain the ability to infect novel hosts, but few data are available regarding the number of possible host range-expanding mutations allowing infection of any given novel host, and the fitness consequences of these mutations on original and novel hosts. To gain insight into the process of host range expansion, we isolated and sequenced 69 independent mutants of the dsRNA bacteriophage Φ6 able to infect the novel host, Pseudomonas pseudoalcaligenes. In total, we found at least 17 unique suites of mutations among these 69 mutants. We assayed fitness for 13 of 17 mutant genotypes on P. pseudoalcaligenes and the standard laboratory host, P. phaseolicola. Mutants exhibited significantly lower fitnesses on P. pseudoalcaligenes compared to P. phaseolicola. Furthermore, 12 of the 13 assayed mutants showed reduced fitness on P. phaseolicola compared to wildtype Φ6, confirming the prevalence of antagonistic pleiotropy during host range expansion. Further experiments revealed that the mechanistic basis of these fitness differences was likely variation in host attachment ability. In addition, using computational protein modeling, we show that host-range expanding mutations occurred in hotspots on the surface of the phage's host attachment protein opposite a putative hydrophobic anchoring domain.",2014 Nov 19,"['Ford, Brian E.', 'Sun, Bruce', 'Carpino, James', 'Chapler, Elizabeth S.', 'Ching, Jane', 'Choi, Yoon', 'Jhun, Kevin', 'Kim, Jung D.', 'Lallos, Gregory G.', 'Morgenstern, Rachelle', 'Singh, Shalini', 'Theja, Sai', 'Dennehy, John J.']",PLoS One,,,True
cbe56b09d64047cba4ee7875c4f55276a0cdf273,PMC,Enterovirus 71-induced autophagy increases viral replication and pathogenesis in a suckling mouse model,http://dx.doi.org/10.1186/s12929-014-0080-4,PMC4237791,25139436,CC BY,"BACKGROUND: We previously reported that Enterovirus 71 (EV71) infection activates autophagy, which promotes viral replication both in vitro and in vivo. In the present study we further investigated whether EV71 infection of neuronal SK-N-SH cells induces an autophagic flux. Furthermore, the effects of autophagy on EV71-related pathogenesis and viral load were evaluated after intracranial inoculation of mouse-adapted EV71 (MP4 strain) into 6-day-old ICR suckling mice. RESULTS: We demonstrated that in EV71-infected SK-N-SH cells, EV71 structural protein VP1 and nonstructural protein 2C co-localized with LC3 and mannose-6-phosphate receptor (MPR, endosome marker) proteins by immunofluorescence staining, indicating amphisome formation. Together with amphisome formation, EV71 induced an autophagic flux, which could be blocked by NH(4)Cl (inhibitor of acidification) and vinblastine (inhibitor of fusion), as demonstrated by Western blotting. Suckling mice intracranially inoculated with EV71 showed EV71 VP1 protein expression (representing EV71 infection) in the cerebellum, medulla, and pons by immunohistochemical staining. Accompanied with these infected brain tissues, increased expression of LC3-II protein as well as formation of LC3 aggregates, autophagosomes and amphisomes were detected. Amphisome formation, which was confirmed by colocalization of EV71-VP1 protein or LC3 puncta and the endosome marker protein MPR. Thus, EV71-infected suckling mice (similar to EV71-infected SK-N-SH cells) also show an autophagic flux. The physiopathological parameters of EV71-MP4 infected mice, including body weight loss, disease symptoms, and mortality were increased compared to those of the uninfected mice. We further blocked EV71-induced autophagy with the inhibitor 3-methyladenine (3-MA), which attenuated the disease symptoms and decreased the viral load in the brain tissues of the infected mice. CONCLUSIONS: In this study, we reveal that EV71 infection of suckling mice induces an amphisome formation accompanied with the autophagic flux in the brain tissues. Autophagy induced by EV71 promotes viral replication and EV71-related pathogenesis.",2014 Aug 20,"['Lee, Ying-Ray', 'Wang, Po-Shun', 'Wang, Jen-Ren', 'Liu, Hsiao-Sheng']",J Biomed Sci,,,True
2f00227d35cee08706713c7085ec576b74ff2f9a,PMC,Is There Still Room for Novel Viral Pathogens in Pediatric Respiratory Tract Infections?,http://dx.doi.org/10.1371/journal.pone.0113570,PMC4239085,25412469,CC BY,"Viruses are the most frequent cause of respiratory disease in children. However, despite the advanced diagnostic methods currently in use, in 20 to 50% of respiratory samples a specific pathogen cannot be detected. In this work, we used a metagenomic approach and deep sequencing to examine respiratory samples from children with lower and upper respiratory tract infections that had been previously found negative for 6 bacteria and 15 respiratory viruses by PCR. Nasal washings from 25 children (out of 250) hospitalized with a diagnosis of pneumonia and nasopharyngeal swabs from 46 outpatient children (out of 526) were studied. DNA reads for at least one virus commonly associated to respiratory infections was found in 20 of 25 hospitalized patients, while reads for pathogenic respiratory bacteria were detected in the remaining 5 children. For outpatients, all the samples were pooled into 25 DNA libraries for sequencing. In this case, in 22 of the 25 sequenced libraries at least one respiratory virus was identified, while in all other, but one, pathogenic bacteria were detected. In both patient groups reads for respiratory syncytial virus, coronavirus-OC43, and rhinovirus were identified. In addition, viruses less frequently associated to respiratory infections were also found. Saffold virus was detected in outpatient but not in hospitalized children. Anellovirus, rotavirus, and astrovirus, as well as several animal and plant viruses were detected in both groups. No novel viruses were identified. Adding up the deep sequencing results to the PCR data, 79.2% of 250 hospitalized and 76.6% of 526 ambulatory patients were positive for viruses, and all other children, but one, had pathogenic respiratory bacteria identified. These results suggest that at least in the type of populations studied and with the sampling methods used the odds of finding novel, clinically relevant viruses, in pediatric respiratory infections are low.",2014 Nov 20,"['Taboada, Blanca', 'Espinoza, Marco A.', 'Isa, Pavel', 'Aponte, Fernando E.', 'Arias-Ortiz, María A.', 'Monge-Martínez, Jesús', 'Rodríguez-Vázquez, Rubén', 'Díaz-Hernández, Fidel', 'Zárate-Vidal, Fernando', 'Wong-Chew, Rosa María', 'Firo-Reyes, Verónica', 'del Río-Almendárez, Carlos N.', 'Gaitán-Meza, Jesús', 'Villaseñor-Sierra, Alberto', 'Martínez-Aguilar, Gerardo', 'Salas-Mier, Ma. del Carmen', 'Noyola, Daniel E.', 'Pérez-Gónzalez, Luis F.', 'López, Susana', 'Santos-Preciado, José I.', 'Arias, Carlos F.']",PLoS One,,,True
2402b2a0cb8aef3abb2e103f0997c61dec6511a0,PMC,Full-Genome Sequence Analysis of a Variant Strain of Porcine Epidemic Diarrhea Virus in South Korea,http://dx.doi.org/10.1128/genomeA.01116-14,PMC4239346,25414491,CC BY,"In March of 2014, a variant of novel porcine epidemic diarrhea virus (PEDV) was first identified in South Korea and found to be most closely related to the U.S. variant strain OH851. The complete genome of the KOR/KNU-1406/2014 strain was sequenced and analyzed to investigate the U.S.-strain-like variant circulating in South Korea.",2014 Nov 20,"['Lee, Sunhee', 'Park, Gun-Seok', 'Shin, Jae-Ho', 'Lee, Changhee']",Genome Announc,,,True
63771fc756683bf14c7f7e169990c7268b35d8ed,PMC,The discriminative capacity of soluble Toll-like receptor (sTLR)2 and sTLR4 in inflammatory diseases,http://dx.doi.org/10.1186/s12865-014-0055-y,PMC4240815,25406630,CC BY,"BACKGROUND: The extracellular domains of cytokine receptors are released during inflammation, but little is known about the shedding of Toll-like receptors (TLR) and whether they can be used as diagnostic biomarkers. METHODS: The release of sTLR2 and sTLR4 was studied in in-vitro stimulations, as well as in-vivo during experimental human endotoxemia (n = 11, 2 ng/kg LPS), and in plasma of 394 patients with infections (infectious mononucleosis, measles, respiratory tract infections, bacterial sepsis and candidemia) or non-infectious inflammation (Crohn’s disease, gout, rheumatoid arthritis, autoinflammatory syndromes and pancreatitis). Using C-statistics, the value of sTLR2 and sTLR4 levels for discrimination between infections and non-infectious inflammatory diseases, as well as between viral and bacterial infections was analyzed. RESULTS: In-vitro, peripheral blood mononuclear cells released sTLR2 and sTLR4 by exposure to microbial ligands. During experimental human endotoxemia, plasma concentrations peaked after 2 hours (sTLR4) and 4 hours (sTLR2). sTLR4 did not correlate with cytokines, but sTLR2 correlated positively with TNFα (r(s) = 0.80, P < 0.05), IL-6 (r(s) = 0.65, P < 0.05), and IL-1Ra (r(s) = 0.57, P = 0.06), and negatively with IL-10 (r(s) = -0.58, P = 0.06), respectively. sTLR4 had a similar area under the ROC curve [AUC] for differentiating infectious and non-infectious inflammation compared to CRP: 0.72 (95% CI 0.66-0.79) versus 0.74 (95% CI 0.69-0.80) [P = 0.80], while sTLR2 had a lower AUC: 0.60 (95% CI 0.54-0.66) [P = 0.0004]. CRP differentiated bacterial infections better from viral infections than sTLR2 and sTLR4: AUC 0.94 (95% CI 0.90-0.96) versus 0.58 (95% CI 0.51-0.64) and 0.75 (95% CI 0.70-0.80), respectively [P < 0.0001 for both]. CONCLUSIONS: sTLRs are released into the circulation, and suggest the possibility to use sTLRs as diagnostic tool in inflammatory conditions.",2014 Nov 19,"['ten Oever, Jaap', 'Kox, Matthijs', 'van de Veerdonk, Frank L', 'Mothapo, Khutso M', 'Slavcovici, Adriana', 'Jansen, Tim L', 'Tweehuysen, Lieke', 'Giamarellos-Bourboulis, Evangelos J', 'Schneeberger, Peter M', 'Wever, Peter C', 'Stoffels, Monique', 'Simon, Anna', 'van der Meer, Jos WM', 'Johnson, Melissa D', 'Kullberg, Bart-Jan', 'Pickkers, Peter', 'Pachot, Alexandre', 'Joosten, Leo AB', 'Netea, Mihai G']",BMC Immunol,,,True
8b47882ebbc8d2e9d217dcc10b2328eff5bf8b46,PMC,Cell Surface Protein Disulfide Isomerase Regulates Natriuretic Peptide Generation of Cyclic Guanosine Monophosphate,http://dx.doi.org/10.1371/journal.pone.0112986,PMC4242536,25419565,CC BY,"RATIONALE: The family of natriuretic peptides (NPs), including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), exert important and diverse actions for cardiovascular and renal homeostasis. The autocrine and paracrine functions of the NPs are primarily mediated through the cellular membrane bound guanylyl cyclase-linked receptors GC-A (NPR-A) and GC-B (NPR-B). As the ligands and receptors each contain disulfide bonds, a regulatory role for the cell surface protein disulfide isomerase (PDI) was investigated. OBJECTIVE: We utilized complementary in vitro and in vivo models to determine the potential role of PDI in regulating the ability of the NPs to generate its second messenger, cyclic guanosine monophosphate. METHODS AND RESULTS: Inhibition of PDI attenuated the ability of ANP, BNP and CNP to generate cGMP in human mesangial cells (HMCs), human umbilical vein endothelial cells (HUVECs), and human aortic smooth muscle cells (HASMCs), each of which were shown to express PDI. In LLC-PK1 cells, where PDI expression was undetectable by immunoblotting, PDI inhibition had a minimal effect on cGMP generation. Addition of PDI to cultured LLC-PK1 cells increased intracellular cGMP generation mediated by ANP. Inhibition of PDI in vivo attenuated NP-mediated generation of cGMP by ANP. Surface Plasmon Resonance demonstrated modest and differential binding of the natriuretic peptides with immobilized PDI in a cell free system. However, PDI was shown to co-localize on the surface of cells with GC-A and GC-B by co-immunoprecpitation and immunohistochemistry. CONCLUSION: These data demonstrate for the first time that cell surface PDI expression and function regulate the capacity of natriuretic peptides to generate cGMP through interaction with their receptors.",2014 Nov 24,"['Pan, Shuchong', 'Chen, Horng H.', 'Correia, Cristina', 'Dai, Haiming', 'Witt, Tyra A.', 'Kleppe, Laurel S.', 'Burnett, John C.', 'Simari, Robert D.']",PLoS One,,,True
98157c4866587f2ad65dbf57f6a7cb5a7699b1e4,PMC,A clinical prediction rule for diagnosing human infections with avian influenza A(H7N9) in a hospital emergency department setting,http://dx.doi.org/10.1186/s12916-014-0127-0,PMC4243192,25091477,CC BY,"BACKGROUND: Human infections with avian influenza A(H7N9) virus are associated with severe illness and high mortality. To better inform triage decisions of hospitalization and management, we developed a clinical prediction rule for diagnosing patients with A(H7N9) and determined its predictive performance. METHODS: Clinical details on presentation of adult patients hospitalized with either A(H7N9)(n = 121) in China from March to May 2013 or other causes of acute respiratory infections (n = 2,603) in Jingzhou City, China from January 2010 through September 2012 were analyzed. A clinical prediction rule was developed using a two-step coefficient-based multivariable logistic regression scoring method and evaluated with internal validation by bootstrapping. RESULTS: In step 1, predictors for A(H7N9) included male sex, poultry exposure history, and fever, haemoptysis, or shortness of breath on history and physical examination. In step 2, haziness or pneumonic consolidation on chest radiographs and leukopenia were also associated with a higher probability of A(H7N9). The observed risk of A(H7N9) was 0.3% for those assigned to the low-risk group and 2.5%, 4.3%, and 44.0% for tertiles 1 through 3, respectively, in the high-risk group. This prediction rule achieved good model performance, with an optimism-corrected sensitivity of 0.93, a specificity of 0.80, and an area under the receiver-operating characteristic curve of 0.96. CONCLUSIONS: A simple decision rule based on data readily obtainable in the setting of patients’ first clinical presentations from the first wave of the A/H7N9 epidemic in China has been developed. This prediction rule has achieved good model performance in predicting their risk of A(H7N9) infection and should be useful in guiding important clinical and public health decisions in a timely and objective manner. Data to be gathered with its use in the current evolving second wave of the A/H7N9 epidemic in China will help to inform its performance in the field and contribute to its further refinement. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-014-0127-0) contains supplementary material, which is available to authorized users.",2014 Aug 5,"['Liao, Qiaohong', 'Ip, Dennis K M', 'Tsang, Tim K', 'Cao, Bin', 'Jiang, Hui', 'Liu, Fengfeng', 'Zheng, Jiandong', 'Peng, Zhibin', 'Wu, Peng', 'Huai, Yang', 'Lau, Eric H Y', 'Feng, Luzhao', 'Leung, Gabriel M', 'Yu, Hongjie', 'Cowling, Benjamin J']",BMC Med,,,False
3a4cf1cc2f583dea77288aa7e114c117a00660b2,PMC,A clinical prediction rule for diagnosing human infections with avian influenza A(H7N9) in a hospital emergency department setting,http://dx.doi.org/10.1186/s12916-014-0127-0,PMC4243192,25091477,CC BY,"BACKGROUND: Human infections with avian influenza A(H7N9) virus are associated with severe illness and high mortality. To better inform triage decisions of hospitalization and management, we developed a clinical prediction rule for diagnosing patients with A(H7N9) and determined its predictive performance. METHODS: Clinical details on presentation of adult patients hospitalized with either A(H7N9)(n = 121) in China from March to May 2013 or other causes of acute respiratory infections (n = 2,603) in Jingzhou City, China from January 2010 through September 2012 were analyzed. A clinical prediction rule was developed using a two-step coefficient-based multivariable logistic regression scoring method and evaluated with internal validation by bootstrapping. RESULTS: In step 1, predictors for A(H7N9) included male sex, poultry exposure history, and fever, haemoptysis, or shortness of breath on history and physical examination. In step 2, haziness or pneumonic consolidation on chest radiographs and leukopenia were also associated with a higher probability of A(H7N9). The observed risk of A(H7N9) was 0.3% for those assigned to the low-risk group and 2.5%, 4.3%, and 44.0% for tertiles 1 through 3, respectively, in the high-risk group. This prediction rule achieved good model performance, with an optimism-corrected sensitivity of 0.93, a specificity of 0.80, and an area under the receiver-operating characteristic curve of 0.96. CONCLUSIONS: A simple decision rule based on data readily obtainable in the setting of patients’ first clinical presentations from the first wave of the A/H7N9 epidemic in China has been developed. This prediction rule has achieved good model performance in predicting their risk of A(H7N9) infection and should be useful in guiding important clinical and public health decisions in a timely and objective manner. Data to be gathered with its use in the current evolving second wave of the A/H7N9 epidemic in China will help to inform its performance in the field and contribute to its further refinement. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-014-0127-0) contains supplementary material, which is available to authorized users.",2014 Aug 5,"['Liao, Qiaohong', 'Ip, Dennis K M', 'Tsang, Tim K', 'Cao, Bin', 'Jiang, Hui', 'Liu, Fengfeng', 'Zheng, Jiandong', 'Peng, Zhibin', 'Wu, Peng', 'Huai, Yang', 'Lau, Eric H Y', 'Feng, Luzhao', 'Leung, Gabriel M', 'Yu, Hongjie', 'Cowling, Benjamin J']",BMC Med,,,True
72b6e571746493f62630cc8eb59cd6fae5cb71e2,PMC,The pathological effects of CCR2+ inflammatory monocytes are amplified by an IFNAR1-triggered chemokine feedback loop in highly pathogenic influenza infection,http://dx.doi.org/10.1186/s12929-014-0099-6,PMC4243311,25407417,CC BY,"BACKGROUND: Highly pathogenic influenza viruses cause high levels of morbidity, including excessive infiltration of leukocytes into the lungs, high viral loads and a cytokine storm. However, the details of how these pathological features unfold in severe influenza infections remain unclear. Accumulation of Gr1 + CD11b + myeloid cells has been observed in highly pathogenic influenza infections but it is not clear how and why they accumulate in the severely inflamed lung. In this study, we selected this cell population as a target to investigate the extreme inflammatory response during severe influenza infection. RESULTS: We established H1N1 IAV-infected mouse models using three viruses of varying pathogenicity and noted the accumulation of a defined Gr1 + CD11b + myeloid population correlating with the pathogenicity. Herein, we reported that CCR2+ inflammatory monocytes are the major cell compartments in this population. Of note, impaired clearance of the high pathogenicity virus prolonged IFN expression, leading to CCR2+ inflammatory monocytes amplifying their own recruitment via an interferon-α/β receptor 1 (IFNAR1)-triggered chemokine loop. Blockage of IFNAR1-triggered signaling or inhibition of viral replication by Oseltamivir significantly suppresses the expression of CCR2 ligands and reduced the influx of CCR2+ inflammatory monocytes. Furthermore, trafficking of CCR2+ inflammatory monocytes from the bone marrow to the lung was evidenced by a CCR2-dependent chemotaxis. Importantly, leukocyte infiltration, cytokine storm and expression of iNOS were significantly reduced in CCR2−/− mice lacking infiltrating CCR2+ inflammatory monocytes, enhancing the survival of the infected mice. CONCLUSIONS: Our results indicated that uncontrolled viral replication leads to excessive production of inflammatory innate immune responses by accumulating CCR2+ inflammatory monocytes, which contribute to the fatal outcomes of high pathogenicity virus infections.",2014 Nov 18,"['Lin, Sue-Jane', 'Lo, Ming', 'Kuo, Rei-Lin', 'Shih, Shin-Ru', 'Ojcius, David M', 'Lu, Jean', 'Lee, Chien-Kuo', 'Chen, Hui-Chen', 'Lin, Meei Yun', 'Leu, Chuen-Miin', 'Lin, Chia-Ni', 'Tsai, Ching-Hwa']",J Biomed Sci,,,True
6ca67d203ed9f4870c85f2289d62ee3c498b5a13,PMC,Imaging analysis of human metapneumovirus-infected cells provides evidence for the involvement of F-actin and the raft-lipid microdomains in virus morphogenesis,http://dx.doi.org/10.1186/s12985-014-0198-8,PMC4243936,25408253,CC BY,"BACKGOUND: Due to difficulties of culturing Human metapneumovirus (HMPV) much of the current understanding of HMPV replication can be inferred from other closely related viruses. The slow rates of virus replication prevent many biochemical analyses of HMPV particles. In this study imaging was used to examine the process of HMPV morphogenesis in individually infected LLC-MK2 cells, and to better characterise the sites of HMPV assembly. This strategy has circumvented the problems associated with slow replication rates and allowed us to characterise both the HMPV particles and the sites of HMPV morphogenesis. METHODS: HMPV-infected LLC-MK2 cells were stained with antibodies that recognised the HMPV fusion protein (F protein), attachment protein (G protein) and matrix protein (M protein), and fluorescent probes that detect GM1 within lipid-raft membranes (CTX-B-AF488) and F-actin (Phalloidin-FITC). The stained cells were examined by confocal microscopy, which allowed imaging of F-actin, GM1 and virus particles in HMPV-infected cells. Cells co-expressing recombinant HMPV G and F proteins formed virus-like particles and were co-stained with antibodies that recognise the recombinant G and F proteins and phalloidin-FITC and CTX-B-AF594, and the distribution of the G and F proteins, GM1 and F-actin determined. RESULTS: HMPV-infected cells stained with anti-F, anti-G or anti-M revealed a filamentous staining pattern, indicating that the HMPV particles have a filamentous morphology. Staining of HMPV-infected cells with anti-G and either phalloidin-FITC or CTX-B-AF488 exhibited extensive co-localisation of these cellular probes within the HMPV filaments. This suggested that lipid-raft membrane domains and F-actin structures are present at the site of the virus morphogenesis, and are subsequently incorporated into the HMPV filaments. Furthermore, the filamentous virus-like particles that form in cells expressing the G protein formed in cellular structures containing GM1 and F-actin, suggesting the G protein contains intrinsic targeting signals to the sites of virus assembly. CONCLUSIONS: These data suggest that HMPV matures as filamentous particles and that virus morphogenesis occurs within lipid-raft microdomains containing localized concentrations of F-actin. The similarity between HMPV morphogenesis and the closely related human respiratory syncytial virus suggests that involvement of F-actin and lipid-raft microdomains in virus morphogenesis may be a common feature of the Pneumovirinae. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-014-0198-8) contains supplementary material, which is available to authorized users.",2014 Nov 19,"['Jumat, Muhammad Raihan', 'Nguyen Huong, Tra', 'Wong, Puisan', 'Loo, Liat Hui', 'Tan, Boon Huan', 'Fenwick, Fiona', 'Toms, Geoffrey L', 'Sugrue, Richard J']",Virol J,,,True
f5b706d0529bfcf7e2d1dfc037df5b6f95fc5ec0,PMC,Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study,http://dx.doi.org/10.1186/s13054-014-0456-6,PMC4243941,25112957,CC BY,"INTRODUCTION: Since 2008, severe cases of emerging human adenovirus type 55 (HAdV-55) in immunocompetent adults have been reported sporadically in China. The clinical features and outcomes of the most critically ill patients with severe acute respiratory distress syndrome (ARDS) caused by HAdV-55 requiring invasive mechanical ventilation (IMV) and/or extracorporeal membrane oxygenation (ECMO) are lacking. METHODS: We conducted a prospective, single-center observational study of pneumonia with ARDS in immunocompetent adults admitted to our respiratory ICU. We prospectively collected and analyzed clinical, laboratory, radiological characteristics, sequential tests of viral load in respiratory tract and blood, treatments and outcomes. RESULTS: The results for a total of five consecutive patients with severe ARDS with confirmed HAdV-55 infection were included. All five patients were immunocompetent young men with a median age of 32 years. The mean time from onset to dyspnea was 5 days. Arterial blood gas analysis at ICU admission revealed profound hypoxia. Mean partial oxygen pressure/fraction of inspired oxygen was 58.1. Mean durations from onset to a single-lobe consolidation shown on chest X-rays (CXRs) and, from the first positive CXR to bilateral multilobar lung infiltrates, were 2 days and 4.8 days, respectively. The viral load was higher than 1 × 10(8) copies in three patients and was 1 × 10(4) in one patient. It was negative in the only patient who survived. The mean duration for noninvasive positive pressure ventilation (NPPV) failure and IMV failure were 30.8 hours and 6.2 days, respectively. Four patients received venovenous ECMO. Four (80%) of the five patients died despite receiving appropriate respiratory support. CONCLUSIONS: HAdV-55 may cause severe ARDS in immunocompetent young men. Persistent high fever, dyspnea and rapid progression to respiratory failure within 2 weeks, together with bilateral consolidations and infiltrates, are the most frequent clinical manifestations of HAdV-55-induced severe ARDS. Viral load monitoring may help predict disease severity and outcome. The NPPV and IMV failure rates were very high, but ECMO may still be the respiratory support therapy of choice. TRIAL REGISTRATION: Clinicaltrials.gov NCT01585922. Registered 20 April 2012",2014 Aug 12,"['Sun, Bing', 'He, Hangyong', 'Wang, Zheng', 'Qu, Jiuxin', 'Li, Xuyan', 'Ban, Chengjun', 'Wan, Jun', 'Cao, Bin', 'Tong, Zhaohui', 'Wang, Chen']",Crit Care,,,True
a1a6c0067edf3605299df62d104c31661bbccaec,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,True
67f6981719f5f6d229ac5ff46e353bb7cb1aaea3,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
0bbb3db3fcea884e703a8ab09176b0b6305a6620,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
32ae76810277fb989a7cbc203079b2ae5bc13c2b,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
e26afacc53f34a9432daf809891b5e519f6c1047,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
464a5110126b27bb1e70948714cef5c8528c2c9e,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
1ea345b58fb3fa32d7fbeaf3e6c236ab6a104abe,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
c17d7f1607f8fa333c799b263c8185d3b3d369ac,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
f67740f11517f204388333d646050566bba9b65b,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
bee2faef06dd2aefa2a126de2e15cbe403562aae,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
063f48cf2d9b53b075433f3bd1a63566feb240db,PMC,"Spatial Analysis of the Distribution, Risk Factors and Access to Medical Resources of Patients with Hepatitis B in Shenzhen, China",http://dx.doi.org/10.3390/ijerph111111505,PMC4245626,25386954,CC BY,"Considering the high morbidity of hepatitis B in China, many epidemiological studies based on classic medical statistical analysis have been started but lack spatial information. However, spatial information such as the spatial distribution, autocorrelation and risk factors of the disease is of great help in studying patients with hepatitis B. This study examined 2851 cases of hepatitis B that were hospitalized in Shenzhen in 2010 and studied the spatial distribution, risk factors and spatial access to health services using spatial interpolation, Pearson correlation analysis and the improved two-step floating catchment area method. The results showed that the spatial distribution of hepatitis B, along with risk factors as well as spatial access to the regional medical resources, was uneven and mainly concentrated in the south and southwest of Shenzhen in 2010. In addition, the distribution characteristics of hepatitis B revealed a positive correlation between four types of service establishments and risk factors for the disease. The Pearson correlation coefficients are 0.566, 0.515, 0.626, 0.538 corresponding to bath centres, beauty salons, massage parlours and pedicure parlours (p < 0.05). Additionally, the allocation of medical resources for hepatitis B is adequate, as most patients could be treated at nearby hospitals.",2014 Nov 7,"['Xi, Yuliang', 'Ren, Fu', 'Liang, Shi', 'Zhang, Jinghua', 'Lin, De-Nan']",Int J Environ Res Public Health,,,True
4b6c86374fd6b66e8d0729a9d32d7cf6a11be71e,PMC,Complete Genome Characterization of Korean Porcine Deltacoronavirus Strain KOR/KNU14-04/2014,http://dx.doi.org/10.1128/genomeA.01191-14,PMC4246158,25428966,CC BY,"In April 2014, porcine deltacoronavirus (PDCoV) was first identified in feces from diarrheic piglets in South Korea and found to be closely related to other PDCoV strains. The complete genome of the Korean PDCoV strain, KOR/KNU14-04/2014, was sequenced and analyzed to characterize PDCoV circulating in South Korea.",2014 Nov 26,"['Lee, Sunhee', 'Lee, Changhee']",Genome Announc,,,True
6b1560c20661e5dea1c1d2c391c1fa68f6cf83ca,PMC,Advances in prevention and therapy of neonatal dairy calf diarrhoea: a systematical review with emphasis on colostrum management and fluid therapy,http://dx.doi.org/10.1186/s13028-014-0075-x,PMC4246539,25431305,CC BY,"Neonatal calf diarrhoea remains the most common cause of morbidity and mortality in preweaned dairy calves worldwide. This complex disease can be triggered by both infectious and non-infectious causes. The four most important enteropathogens leading to neonatal dairy calf diarrhoea are Escherichia coli, rota- and coronavirus, and Cryptosporidium parvum. Besides treating diarrhoeic neonatal dairy calves, the veterinarian is the most obvious person to advise the dairy farmer on prevention and treatment of this disease. This review deals with prevention and treatment of neonatal dairy calf diarrhoea focusing on the importance of a good colostrum management and a correct fluid therapy.",2014 Nov 25,"['Meganck, Vanessa', 'Hoflack, Geert', 'Opsomer, Geert']",Acta Vet Scand,,,True
8dd45f6f44956863508e44c1e6c7338b51a7524d,PMC,Characterizing Influenza surveillance systems performance: application of a Bayesian hierarchical statistical model to Hong Kong surveillance data,http://dx.doi.org/10.1186/1471-2458-14-850,PMC4246552,25127906,CC BY,"BACKGROUND: Infectious disease surveillance is a process the product of which reflects both actual disease trends and public awareness of the disease. Decisions made by patients, health care providers, and public health professionals about seeking and providing health care and about reporting cases to health authorities are all influenced by the information environment, which changes constantly. Biases are therefore imbedded in surveillance systems; these biases need to be characterized to provide better situational awareness for decision-making purposes. Our goal is to develop a statistical framework to characterize influenza surveillance systems, particularly their correlation with the information environment. METHODS: We identified Hong Kong influenza surveillance data systems covering healthcare providers, laboratories, daycare centers and residential care homes for the elderly. A Bayesian hierarchical statistical model was developed to examine the statistical relationships between the influenza surveillance data and the information environment represented by alerts from HealthMap and web queries from Google. Different models were fitted for non-pandemic and pandemic periods and model goodness-of-fit was assessed using common model selection procedures. RESULTS: Some surveillance systems — especially ad hoc systems developed in response to the pandemic flu outbreak — are more correlated with the information environment than others. General practitioner (percentage of influenza-like-illness related patient visits among all patient visits) and laboratory (percentage of specimen tested positive) seem to proportionally reflect the actual disease trends and are less representative of the information environment. Surveillance systems using influenza-specific code for reporting tend to reflect biases of both healthcare seekers and providers. CONCLUSIONS: This study shows certain influenza surveillance systems are less correlated with the information environment than others, and therefore, might represent more reliable indicators of disease activity in future outbreaks. Although the patterns identified in this study might change in future outbreaks, the potential susceptibility of surveillance data is likely to persist in the future, and should be considered when interpreting surveillance data. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2458-14-850) contains supplementary material, which is available to authorized users.",2014 Aug 15,"['Zhang, Ying', 'Arab, Ali', 'Cowling, Benjamin J', 'Stoto, Michael A']",BMC Public Health,,,True
f66963a9155d44a7f734c0f1d30cab3371cd99fa,PMC,Comparative serum proteome expression of the steroid-induced femoral head osteonecrosis in adults,http://dx.doi.org/10.3892/etm.2014.2069,PMC4247312,25452779,CC BY,"Steroid-induced osteonecrosis of the femoral head (SONFH) is a disabling, aseptic and ischemic disease that develops following steroid therapy. The pathogenesis of SONFH is unclear, so the early diagnosis and treatment for this disease is yet to be established. The purpose of the present study was to identify potential biomarkers for SONFH. The differential expression of serum proteins from patients with SONFH and healthy volunteers was analyzed by the proteomics method. The protein samples were labeled and subjected to isoelectric focusing and two-dimensional gel electrophoresis. The resultant protein spots were matched and quantified by an imaging analysis system. The differentially-expressed protein spots were subjected to in-gel trypsin digestion followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Significantly lower levels of complement component 3 (C3), C4, inter-α-trypsin inhibitor heavy chain H4 and α-2-macroglobulin were found in the serum of patients with SONFH. These proteins are reported to be actively involved in intravascular coagulation, apoptosis and reactive oxygen species imbalance, indicating that multiple pathological reactions occur in SONFH and these proteins may serve as potential biomarkers for the diagnosis of SONFH.",2015 Jan 12,"['CHEN, YUXIAN', 'ZENG, CHUN', 'ZENG, HUA', 'ZHANG, RONGKAI', 'YE, ZHIQIANG', 'XING, BANGRONG', 'HU, KUNHUA', 'LI, MINGTAO', 'CAI, DAO ZHANG']",Exp Ther Med,,,True
8fcf1d545d5c10fbe83bbbd9dab8391fb748be7f,PMC,The ability to suppress macrophage-mediated inflammation in orbital fat stem cells is controlled by miR-671-5p,http://dx.doi.org/10.1186/scrt486,PMC4247678,25124290,CC BY,"INTRODUCTION: Our previous works demonstrated that systemic orbital fat-derived stem cell (OFSC) transplantation was effective in ameliorating lipopolysaccharide (LPS)-induced extensive acute lung injury (ALI) in vivo mainly through paracrine regulation of macrophage-mediated cytokine-storm. In this study, we explore the molecular mechanism(s) of OFSCs regulating macrophage activity in a cytokine-inducible fashion. METHODS: LPS (100 ng/ml)-activated macrophages were treated by conditioned medium from OFSCs (OFSCs-CM) or non-contact cultured with OFSCs for 6 hours. The potency of OFSCs on macrophage proliferation and pro-inflammation ability were determined. Expression levels of pro-inflammatory cytokines in macrophages, inducible immuno-modulatory factors in OFSCs, were investigated. Deep sequencing analysis as well as interaction between microRNA (miRNA) and genes of immuno-modulators in OFSCs induced by activated macrophages was predicted by miRTar. Transfection of miRNA inhibitor into OFSCs was performed. Real-time RT-PCR and transplantation of OFSCs into mice with LPS-induced ALI confirmed the in vitro and in vivo mechanism. RESULTS: The paracrine effect of OFSCs on inhibition of macrophage pro-inflammatory cytokine release was more potent than induction of macrophage G0/G1 cell cycle arrest. OFSCs-CM suppressed LPS-induced inducible nitric oxide synthetase and the pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1 alpha, and IL-1 beta expression in macrophages. Under non-contact culture, LPS-activated macrophages effectively triggered the expression of soluble immuno-modulating factors in OFSCs, i.e., IL-10, IL-1 receptor antagonist (IL-1 RA), indoleamine 2,3-dioxygenase, and soluble TNF receptor type II (sTNF RII). Under miRTar prediction, miR-671-5p was identified as a critical microRNA in regulation of multiple immune-modulating factors in OFSCs response to macrophages. The baseline level of miR-671-5p was high in OFSCs, and down-regulation of miR-671-5p upon co-culture with activated macrophages was observed. MiR-671-5p inhibitor transfection into OFSCs selectively enhanced the IL-1 RA and sTNF RII expressions. In addition, inhibition of miR-671-5p in OFSCs enhanced the anti-inflammatory ability against LPS-induced ALI. CONCLUSION: The paracrine effect of OFSCs inhibits the pro-inflammatory ability and proliferation of macrophages. The immune-modulation capacity of OFSCs can be triggered by activated macrophages, and down-regulation of miR-671-5p enhances OFSC immuno-modulation ability by up-regulating IL-1 RA and sTNF RII expression.",2014 Aug 13,"['Lien, Gi-Shih', 'Liu, Jen-Fang', 'Chien, Ming-Hsien', 'Hsu, Wei-Tse', 'Chang, Tzu-Hao', 'Ku, Chia-Chi', 'Ji, Andrea Tung-Qian', 'Tan, Peng', 'Hsieh, Ting-Lieh', 'Lee, Liang-Ming', 'Ho, Jennifer H']",Stem Cell Res Ther,,,True
3559efd0d0327a8262022dcdd40d01a6f468cb82,PMC,Persistent viremia by a novel parvovirus in a slow loris (Nycticebus coucang) with diffuse histiocytic sarcoma,http://dx.doi.org/10.3389/fmicb.2014.00655,PMC4249460,25520709,CC BY,"Cancer is one of the leading health concerns for human and animal health. Since the tumorigenesis process is not completely understood and it is known that some viruses can induce carcinogenesis, it is highly important to identify novel oncoviruses and extensively study underlying oncogenic mechanisms. Here, we investigated a case of diffuse histiocytic sarcoma in a 22 year old slow loris (Nycticebus coucang), using a broad spectrum virus discovery technique. A novel parvovirus was discovered and the phylogenetic analysis performed on its fully sequenced genome demonstrated that it represents the first member of a novel genus. The possible causative correlation between this virus and the malignancy was further investigated and 20 serum and 61 organ samples from 25 animals (N. coucang and N. pygmaeus) were screened for the novel virus but only samples collected from the originally infected animal were positive. The virus was present in all tested organs (intestine, liver, spleen, kidneys, and lungs) and in all banked serum samples collected up to 8 years before death. All attempts to identify a latent viral form (integrated or episomal) were unsuccessful and the increase of variation in the viral sequences during the years was consistent with absence of latency. Since it is well known that parvoviruses are dependent on cell division to successfully replicate, we hypothesized that the virus could have benefitted from the constantly dividing cancer cells and may not have been the cause of the histiocytic sarcoma. It is also possible to conjecture that the virus had a role in delaying the tumor progression and this report might bring new exciting opportunities in recognizing viruses to be used in cancer virotherapy.",2014 Dec 1,"['Canuti, Marta', 'Williams, Cathy V.', 'Gadi, Sashi R.', 'Jebbink, Maarten F.', 'Oude Munnink, Bas B.', 'Jazaeri Farsani, Seyed Mohammad', 'Cullen, John M.', 'van der Hoek, Lia']",Front Microbiol,,,True
d8225446cd198441e0d3f3d61387058082932bbf,PMC,"Molecular Detection, Phylogenetic Analysis, and Identification of Transcription Motifs in Feline Leukemia Virus from Naturally Infected Cats in Malaysia",http://dx.doi.org/10.1155/2014/760961,PMC4251355,25506469,CC BY,"A nested PCR assay was used to determine the viral RNA and proviral DNA status of naturally infected cats. Selected samples that were FeLV-positive by PCR were subjected to sequencing, phylogenetic analysis, and motifs search. Of the 39 samples that were positive for FeLV p27 antigen, 87.2% (34/39) were confirmed positive with nested PCR. FeLV proviral DNA was detected in 38 (97.3%) of p27-antigen negative samples. Malaysian FeLV isolates are found to be highly similar with a homology of 91% to 100%. Phylogenetic analysis revealed that Malaysian FeLV isolates divided into two clusters, with a majority (86.2%) sharing similarity with FeLV-K01803 and fewer isolates (13.8%) with FeLV-GM1 strain. Different enhancer motifs including NF-GMa, Krox-20/WT1I-del2, BAF1, AP-2, TBP, TFIIF-beta, TRF, and TFIID are found to occur either in single, duplicate, triplicate, or sets of 5 in different positions within the U3-LTR-gag region. The present result confirms the occurrence of FeLV viral RNA and provirus DNA in naturally infected cats. Malaysian FeLV isolates are highly similar, and a majority of them are closely related to a UK isolate. This study provides the first molecular based information on FeLV in Malaysia. Additionally, different enhancer motifs likely associated with FeLV related pathogenesis have been identified.",2014 Nov 17,"['Bande, Faruku', 'Arshad, Siti Suri', 'Hassan, Latiffah', 'Zakaria, Zunita']",Vet Med Int,,,False
288e7bf5d16ac18731d2f1ee7db6d6ed2a720cc2,PMC,"Molecular Detection, Phylogenetic Analysis, and Identification of Transcription Motifs in Feline Leukemia Virus from Naturally Infected Cats in Malaysia",http://dx.doi.org/10.1155/2014/760961,PMC4251355,25506469,CC BY,"A nested PCR assay was used to determine the viral RNA and proviral DNA status of naturally infected cats. Selected samples that were FeLV-positive by PCR were subjected to sequencing, phylogenetic analysis, and motifs search. Of the 39 samples that were positive for FeLV p27 antigen, 87.2% (34/39) were confirmed positive with nested PCR. FeLV proviral DNA was detected in 38 (97.3%) of p27-antigen negative samples. Malaysian FeLV isolates are found to be highly similar with a homology of 91% to 100%. Phylogenetic analysis revealed that Malaysian FeLV isolates divided into two clusters, with a majority (86.2%) sharing similarity with FeLV-K01803 and fewer isolates (13.8%) with FeLV-GM1 strain. Different enhancer motifs including NF-GMa, Krox-20/WT1I-del2, BAF1, AP-2, TBP, TFIIF-beta, TRF, and TFIID are found to occur either in single, duplicate, triplicate, or sets of 5 in different positions within the U3-LTR-gag region. The present result confirms the occurrence of FeLV viral RNA and provirus DNA in naturally infected cats. Malaysian FeLV isolates are highly similar, and a majority of them are closely related to a UK isolate. This study provides the first molecular based information on FeLV in Malaysia. Additionally, different enhancer motifs likely associated with FeLV related pathogenesis have been identified.",2014 Nov 17,"['Bande, Faruku', 'Arshad, Siti Suri', 'Hassan, Latiffah', 'Zakaria, Zunita']",Vet Med Int,,,True
fb515d76fcd0dcf243425b037693e00c9a1afd34,PMC,Fuse me IFITM can!,http://dx.doi.org/10.1186/s12977-014-0104-x,PMC4251678,25422110,CC BY,,2014 Nov 25,"Fassati, Ariberto",Retrovirology,,,True
4ef4cb3ed4814b1afceebb92b410e53fd5646f4e,PMC,IFITM proteins are incorporated onto HIV-1 virion particles and negatively imprint their infectivity,http://dx.doi.org/10.1186/s12977-014-0103-y,PMC4251951,25422070,CC BY,"BACKGROUND: Interferon induced transmembrane proteins 1, 2 and 3 (IFITMs) belong to a family of highly related antiviral factors that have been shown to interfere with a large spectrum of viruses including Filoviruses, Coronaviruses, Influenza virus, Dengue virus and HIV-1. In all these cases, the reported mechanism of antiviral inhibition indicates that the pool of IFITM proteins present in target cells blocks incoming viral particles in endosomal vesicles where they are subsequently degraded. RESULTS: In this study, we describe an additional mechanism through which IFITMs block HIV-1. In virus-producing cells, IFITMs coalesce with forming virions and are incorporated into viral particles. Expression of IFITMs during virion assembly leads to the production of virion particles of decreased infectivity that are mostly affected during entry in target cells. This mechanism of inhibition is exerted against different retroviruses and does not seem to be dependent on the type of Envelope present on retroviral particles. CONCLUSIONS: The results described here identify a novel mechanism through which IFITMs affect HIV-1 infectivity during the late phases of the viral life cycle. Put in the context of data obtained by other laboratories, these results indicate that IFITMs can target HIV at two distinct moments of its life cycle, in target cells as well as in virus-producing cells. These results raise the possibility that IFITMs could similarly affect distinct steps of the life cycle of a number of other viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-014-0103-y) contains supplementary material, which is available to authorized users.",2014 Nov 25,"['Tartour, Kevin', 'Appourchaux, Romain', 'Gaillard, Julien', 'Nguyen, Xuan-Nhi', 'Durand, Stéphanie', 'Turpin, Jocelyn', 'Beaumont, Elodie', 'Roch, Emmanuelle', 'Berger, Gregory', 'Mahieux, Renaud', 'Brand, Denys', 'Roingeard, Philippe', 'Cimarelli, Andrea']",Retrovirology,,,True
85172df4b29cb30c4e98011ed79e9da2ca63fbd6,PMC,Transcriptional profiling of the spleen in progressive visceral leishmaniasis reveals mixed expression of type 1 and type 2 cytokine-responsive genes,http://dx.doi.org/10.1186/s12865-014-0038-z,PMC4253007,25424735,CC BY,"BACKGROUND: The Syrian golden hamster (Mesocricetus aureus) has been used as a model to study infections caused by a number of human pathogens. Studies of immunopathogenesis in hamster infection models are challenging because of the limited availability of reagents needed to define cellular and molecular determinants. RESULTS: We sequenced a hamster cDNA library and developed a first-generation custom cDNA microarray that included 5131 unique cDNAs enriched for immune response genes. We used this microarray to interrogate the hamster spleen response to Leishmania donovani, an intracellular protozoan that causes visceral leishmaniasis. The hamster model of visceral leishmaniasis is of particular interest because it recapitulates clinical and immunopathological features of human disease, including cachexia, massive splenomegaly, pancytopenia, immunosuppression, and ultimately death. In the microarray a differentially expressed transcript was identified as having at least a 2-fold change in expression between uninfected and infected groups and a False Discovery Rate of <5%. Following a relatively silent early phase of infection (at 7 and 14 days post-infection only 8 and 24 genes, respectively, were differentially expressed), there was dramatic upregulation of inflammatory and immune-related genes in the spleen (708 differentially expressed genes were evident at 28 days post-infection). The differentially expressed transcripts included genes involved in inflammation, immunity, and immune cell trafficking. Of particular interest there was concomitant upregulation of the IFN-γ and interleukin (IL)-4 signaling pathways, with increased expression of a battery of IFN-γ- and IL-4-responsive genes. The latter included genes characteristic of alternatively activated macrophages. CONCLUSIONS: Transcriptional profiling was accomplished in the Syrian golden hamster, for which a fully annotated genome is not available. In the hamster model of visceral leishmaniasis, a robust and functional IFN-γ response did not restrain parasite load and progression of disease. This supports the accumulating evidence that macrophages are ineffectively activated to kill the parasite. The concomitant expression of IL-4/IL-13 and their downstream target genes, some of which were characteristic of alternative macrophage activation, are likely to contribute to this. Further dissection of mechanisms that lead to polarization of macrophages toward a permissive state is needed to fully understand the pathogenesis of visceral leishmaniasis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12865-014-0038-z) contains supplementary material, which is available to authorized users.",2014 Nov 26,"['Espitia, Claudia M', 'Saldarriaga, Omar A', 'Travi, Bruno L', 'Osorio, E Yaneth', 'Hernandez, Alvaro', 'Band, Mark', 'Patel, Mandakini J', 'Medina, Audrie A', 'Cappello, Michael', 'Pekosz, Andrew', 'Melby, Peter C']",BMC Immunol,,,True
70419bf8c8f69f99d3127967e958ead655296b3e,PMC,Cryptosporidiosis caused by Cryptosporidium parvum subtype IIdA15G1 at a dairy farm in Northwestern China,http://dx.doi.org/10.1186/s13071-014-0529-z,PMC4254006,25430474,CC BY,"BACKGROUND: Cryptosporidium spp. are zoonotic parasites responsible for diarrhoeal diseases in animals and humans worldwide. Cattle are the most common mammalian species in which Cryptosporidium is detected, with pre-weaned calves considered to be reservoirs for zoonotic C. parvum. In October 2013, severe diarrhoea was observed in 396 pre-weaned calves at a farm in the Ningxia Autonomous Region of Northwestern China. 356 of the infected calves died despite antibiotic therapy. FINDINGS: 252 faecal samples were collected from the investigated farm. The identity of Cryptosporidium species was determined by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) analysis, and by DNA sequence analysis of the small subunit (SSU) rRNA gene. C. parvum was subtyped using sequence analysis of the 60 kDa glycoprotein (gp60) gene. The highest infection rate of 83.3% (40/48) was seen in 2–3-week-old calves with diarrhoea, corresponding to the age at which animals died. Three Cryptosporidium species were identified, including C. parvum (n = 51), C. bovis (n = 1), and C. ryanae (n = 1). All C. parvum isolates were further identified as subtype IIdA15G1. CONCLUSIONS: Cryptosporidium parvum was likely to be most responsible for diarrhoea and death. This is the first report of a cryptosporidiosis outbreak caused by C. parvum IIdA15G1 in Chinese dairy cattle.",2014 Nov 27,"['Cui, Zhaohui', 'Wang, Rongjun', 'Huang, Jianying', 'Wang, Haiyan', 'Zhao, Jinfeng', 'Luo, Nannan', 'Li, Junqiang', 'Zhang, Zhenjie', 'Zhang, Longxian']",Parasit Vectors,,,True
9138f2909ac88cdf8463d08e4559197edc2c60ee,PMC,Identification of a novel nidovirus in an outbreak of fatal respiratory disease in ball pythons (Python regius),http://dx.doi.org/10.1186/1743-422X-11-144,PMC4254391,25106433,CC BY,"BACKGROUND: Respiratory infections are important causes of morbidity and mortality in reptiles; however, the causative agents are only infrequently identified. FINDINGS: Pneumonia, tracheitis and esophagitis were reported in a collection of ball pythons (Python regius). Eight of 12 snakes had evidence of bacterial pneumonia. High-throughput sequencing of total extracted nucleic acids from lung, esophagus and spleen revealed a novel nidovirus. PCR indicated the presence of viral RNA in lung, trachea, esophagus, liver, and spleen. In situ hybridization confirmed the presence of intracellular, intracytoplasmic viral nucleic acids in the lungs of infected snakes. Phylogenetic analysis based on a 1,136 amino acid segment of the polyprotein suggests that this virus may represent a new species in the subfamily Torovirinae. CONCLUSIONS: This report of a novel nidovirus in ball pythons may provide insight into the pathogenesis of respiratory disease in this species and enhances our knowledge of the diversity of nidoviruses.",2014 Aug 8,"['Uccellini, Lorenzo', 'Ossiboff, Robert J', 'de Matos, Ricardo EC', 'Morrisey, James K', 'Petrosov, Alexandra', 'Navarrete-Macias, Isamara', 'Jain, Komal', 'Hicks, Allison L', 'Buckles, Elizabeth L', 'Tokarz, Rafal', 'McAloose, Denise', 'Lipkin, Walter Ian']",Virol J,,,True
e488697a5a07d8a7077f4dae04f386ff038fba5b,PMC,Elevated dietary zinc oxide levels do not have a substantial effect on porcine reproductive and respiratory syndrome virus (PPRSV) vaccination and infection,http://dx.doi.org/10.1186/1743-422X-11-140,PMC4254400,25103309,CC BY,"BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important infectious agents for the swine industry worldwide. Zinc (Zn) salts, which are widely used as a dietary supplement in swine nutrition, have shown antiviral effects in vitro as well as in vivo. The purpose of this study was to determine the influence of dietary zinc oxide supplementation on vaccination and challenge infection with PRRSV. FINDINGS: The clinical course of PRRS and the success of vaccination with an experimental inactivated vaccine were compared between animals receiving a conventional diet (50 ppm Zn, control group) and diets supplemented with Zn oxide (ZnO) at final Zn concentrations of 150 or 2,500 ppm. Pigs receiving higher dietary Zn levels showed a tendency towards higher neutralizing antibody levels after infection, while dietary Zn levels did not substantially influence the number of antiviral IFN-gamma secreting cells (IFN-gamma-SC) or percentages of blood immune cell subsets after infection. Finally, feeding higher dietary Zn levels reduced neither clinical symptoms nor viral loads. CONCLUSIONS: Our results suggest that higher levels of dietary ZnO do not have the potential to stimulate or modulate systemic immune responses after vaccination and heterologous PRRSV infection to an extent that could improve the clinical and virological outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1743-422X-11-140) contains supplementary material, which is available to authorized users.",2014 Aug 8,"['Chai, Weidong', 'Wang, Zhenya', 'Janczyk, Pawel', 'Twardziok, Sven', 'Blohm, Ulrike', 'Osterrieder, Nikolaus', 'Burwinkel, Michael']",Virol J,,,True
c458f17d49c0b39b4ac6fece7f994fd9f6ede076,PMC,Identification and characterization of unrecognized viruses in stool samples of non-polio acute flaccid paralysis children by simplified VIDISCA,http://dx.doi.org/10.1186/1743-422X-11-146,PMC4254409,25112200,CC BY,"BACKGROUND: The use of sequence independent methods combined with next generation sequencing for identification purposes in clinical samples appears promising and exciting results have been achieved to understand unexplained infections. One sequence independent method, Virus Discovery based on cDNA Amplified Fragment Length Polymorphism (VIDISCA) is capable of identifying viruses that would have remained unidentified in standard diagnostics or cell cultures. METHODS: VIDISCA is normally combined with next generation sequencing, however, we set up a simplified VIDISCA which can be used in case next generation sequencing is not possible. Stool samples of 10 patients with unexplained acute flaccid paralysis showing cytopathic effect in rhabdomyosarcoma cells and/or mouse cells were used to test the efficiency of this method. To further characterize the viruses, VIDISCA-positive samples were amplified and sequenced with gene specific primers. RESULTS: Simplified VIDISCA detected seven viruses (70%) and the proportion of eukaryotic viral sequences from each sample ranged from 8.3 to 45.8%. Human enterovirus EV-B97, EV-B100, echovirus-9 and echovirus-21, human parechovirus type-3, human astrovirus probably a type-3/5 recombinant, and tetnovirus-1 were identified. Phylogenetic analysis based on the VP1 region demonstrated that the human enteroviruses are more divergent isolates circulating in the community. CONCLUSION: Our data support that a simplified VIDISCA protocol can efficiently identify unrecognized viruses grown in cell culture with low cost, limited time without need of advanced technical expertise. Also complex data interpretation is avoided thus the method can be used as a powerful diagnostic tool in limited resources. Redesigning the routine diagnostics might lead to additional detection of previously undiagnosed viruses in clinical samples of patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1743-422X-11-146) contains supplementary material, which is available to authorized users.",2014 Aug 12,"['Shaukat, Shahzad', 'Angez, Mehar', 'Alam, Muhammad Masroor', 'Jebbink, Maarten F', 'Deijs, Martin', 'Canuti, Marta', 'Sharif, Salmaan', 'de Vries, Michel', 'Khurshid, Adnan', 'Mahmood, Tariq', 'van der Hoek, Lia', 'Zaidi, Syed Sohail Zahoor']",Virol J,,,True
7cb5fb2bfbc900ec54fa097f45d3e43cd160bd3d,PMC,"Full-Length Genome Sequence of a Variant Porcine Epidemic Diarrhea Virus Strain, CH/GDZQ/2014, Responsible for a Severe Outbreak of Diarrhea in Piglets in Guangdong, China, 2014",http://dx.doi.org/10.1128/genomeA.01239-14,PMC4256184,25477403,CC BY,"The full-length genome sequence of a variant porcine epidemic diarrhea virus (PEDV) strain, CH/GDZQ/2014, was determined. The isolate was a variant strain with a relatively far relationship with the PEDV strains previously identified in the same area between 2011 and 2012 and was genetically distinct from the CV777-based vaccine strain currently being used in China.",2014 Dec 4,"['Song, Deping', 'Chen, Yanjun', 'Peng, Qi', 'Huang, Dongyan', 'Zhang, Tiansheng', 'Huang, Tao', 'Zhang, Fanfan', 'Zhou, Xinrong', 'Tang, Yuxin']",Genome Announc,,,True
d1fc5729ff932800c93dbe279b36ea3c53375708,PMC,A Novel Psittacine Adenovirus Identified During an Outbreak of Avian Chlamydiosis and Human Psittacosis: Zoonosis Associated with Virus-Bacterium Coinfection in Birds,http://dx.doi.org/10.1371/journal.pntd.0003318,PMC4256287,25474263,CC BY,"Chlamydophila psittaci is found worldwide, but is particularly common among psittacine birds in tropical and subtropical regions. While investigating a human psittacosis outbreak that was associated with avian chlamydiosis in Hong Kong, we identified a novel adenovirus in epidemiologically linked Mealy Parrots, which was not present in healthy birds unrelated to the outbreak or in other animals. The novel adenovirus (tentatively named Psittacine adenovirus HKU1) was most closely related to Duck adenovirus A in the Atadenovirus genus. Sequencing showed that the Psittacine adenovirus HKU1 genome consists of 31,735 nucleotides. Comparative genome analysis showed that the Psittacine adenovirus HKU1 genome contains 23 open reading frames (ORFs) with sequence similarity to known adenoviral genes, and six additional ORFs at the 3′ end of the genome. Similar to Duck adenovirus A, the novel adenovirus lacks LH1, LH2 and LH3, which distinguishes it from other viruses in the Atadenovirus genus. Notably, fiber-2 protein, which is present in Aviadenovirus but not Atadenovirus, is also present in Psittacine adenovirus HKU1. Psittacine adenovirus HKU1 had pairwise amino acid sequence identities of 50.3–54.0% for the DNA polymerase, 64.6–70.7% for the penton protein, and 66.1–74.0% for the hexon protein with other Atadenovirus. The C. psittaci bacterial load was positively correlated with adenovirus viral load in the lung. Immunostaining for fiber protein expression was positive in lung and liver tissue cells of affected parrots, confirming active viral replication. No other viruses were found. This is the first documentation of an adenovirus-C. psittaci co-infection in an avian species that was associated with a human outbreak of psittacosis. Viral-bacterial co-infection often increases disease severity in both humans and animals. The role of viral-bacterial co-infection in animal-to-human transmission of infectious agents has not received sufficient attention and should be emphasized in the investigation of disease outbreaks in human and animals.",2014 Dec 4,"['To, Kelvin K. W.', 'Tse, Herman', 'Chan, Wan-Mui', 'Choi, Garnet K. Y.', 'Zhang, Anna J. X.', 'Sridhar, Siddharth', 'Wong, Sally C. Y.', 'Chan, Jasper F. W.', 'Chan, Andy S. F.', 'Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Lo, Janice Y. C.', 'Chan, Kwok-Hung', 'Cheng, Vincent C. C.', 'Yuen, Kwok-Yung']",PLoS Negl Trop Dis,,,True
450b87fb527fca46dfc933e35d4de041bf170bd9,PMC,"Emergence of MERS-CoV in the Middle East: Origins, Transmission, Treatment, and Perspectives",http://dx.doi.org/10.1371/journal.ppat.1004457,PMC4256428,25474536,CC BY,,2014 Dec 4,"['Sharif-Yakan, Ahmad', 'Kanj, Souha S.']",PLoS Pathog,,,True
80b0747661793f45be4bc78da3223c63354331ca,PMC,Rapid Identification of Black Grain Eumycetoma Causative Agents Using Rolling Circle Amplification,http://dx.doi.org/10.1371/journal.pntd.0003368,PMC4256478,25474355,CC BY,"Accurate identification of mycetoma causative agent is a priority for treatment. However, current identification tools are far from being satisfactory for both reliable diagnosis and epidemiological investigations. A rapid, simple, and highly efficient molecular based method for identification of agents of black grain eumycetoma is introduced, aiming to improve diagnostic in endemic areas. Rolling Circle Amplification (RCA) uses species-specific padlock probes and isothermal DNA amplification. The tests were based on ITS sequences and developed for Falciformispora senegalensis, F. tompkinsii, Madurella fahalii, M. mycetomatis, M. pseudomycetomatis, M. tropicana, Medicopsis romeroi, and Trematosphaeria grisea. With the isothermal RCA assay, 62 isolates were successfully identified with 100% specificity and no cross reactivity or false results. The main advantage of this technique is the low-cost, high specificity, and simplicity. In addition, it is highly reproducible and can be performed within a single day.",2014 Dec 4,"['Ahmed, Sarah A.', 'van den Ende, Bert H. G. Gerrits', 'Fahal, Ahmed H.', 'van de Sande, Wendy W. J.', 'de Hoog, G. S.']",PLoS Negl Trop Dis,,,True
04605d35cd46d435e96dc82778096c879327a5dc,PMC,Rapid Identification of Black Grain Eumycetoma Causative Agents Using Rolling Circle Amplification,http://dx.doi.org/10.1371/journal.pntd.0003368,PMC4256478,25474355,CC BY,"Accurate identification of mycetoma causative agent is a priority for treatment. However, current identification tools are far from being satisfactory for both reliable diagnosis and epidemiological investigations. A rapid, simple, and highly efficient molecular based method for identification of agents of black grain eumycetoma is introduced, aiming to improve diagnostic in endemic areas. Rolling Circle Amplification (RCA) uses species-specific padlock probes and isothermal DNA amplification. The tests were based on ITS sequences and developed for Falciformispora senegalensis, F. tompkinsii, Madurella fahalii, M. mycetomatis, M. pseudomycetomatis, M. tropicana, Medicopsis romeroi, and Trematosphaeria grisea. With the isothermal RCA assay, 62 isolates were successfully identified with 100% specificity and no cross reactivity or false results. The main advantage of this technique is the low-cost, high specificity, and simplicity. In addition, it is highly reproducible and can be performed within a single day.",2014 Dec 4,"['Ahmed, Sarah A.', 'van den Ende, Bert H. G. Gerrits', 'Fahal, Ahmed H.', 'van de Sande, Wendy W. J.', 'de Hoog, G. S.']",PLoS Negl Trop Dis,,,False
88f1de42ca135e68ca9aa6a10081091fc4443028,PMC,Progress toward universal health coverage in ASEAN,http://dx.doi.org/10.3402/gha.v7.25856,PMC4256544,25476931,CC BY,"BACKGROUND: The Association of Southeast Asian Nations (ASEAN) is characterized by much diversity in terms of geography, society, economic development, and health outcomes. The health systems as well as healthcare structure and provisions vary considerably. Consequently, the progress toward Universal Health Coverage (UHC) in these countries also varies. This paper aims to describe the progress toward UHC in the ASEAN countries and discuss how regional integration could influence UHC. DESIGN: Data reported in this paper were obtained from published literature, reports, and gray literature available in the ASEAN countries. We used both online and manual search methods to gather the information and ‘snowball’ further data. RESULTS: We found that, in general, ASEAN countries have made good progress toward UHC, partly due to relatively sustained political commitments to endorse UHC in these countries. However, all the countries in ASEAN are facing several common barriers to achieving UHC, namely 1) financial constraints, including low levels of overall and government spending on health; 2) supply side constraints, including inadequate numbers and densities of health workers; and 3) the ongoing epidemiological transition at different stages characterized by increasing burdens of non-communicable diseases, persisting infectious diseases, and reemergence of potentially pandemic infectious diseases. The ASEAN Economic Community's (AEC) goal of regional economic integration and a single market by 2015 presents both opportunities and challenges for UHC. Healthcare services have become more available but health and healthcare inequities will likely worsen as better-off citizens of member states might receive more benefits from the liberalization of trade policy in health, either via regional outmigration of health workers or intra-country health worker movement toward private hospitals, which tend to be located in urban areas. For ASEAN countries, UHC should be explicitly considered to mitigate deleterious effects of economic integration. Political commitments to safeguard health budgets and increase health spending will be necessary given liberalization's risks to health equity as well as migration and population aging which will increase demand on health systems. There is potential to organize select health services regionally to improve further efficiency. CONCLUSIONS: We believe that ASEAN has significant potential to become a force for better health in the region. We hope that all ASEAN citizens can enjoy higher health and safety standards, comprehensive social protection, and improved health status. We believe economic and other integration efforts can further these aspirations.",2014 Dec 3,"['Van Minh, Hoang', 'Pocock, Nicola Suyin', 'Chaiyakunapruk, Nathorn', 'Chhorvann, Chhea', 'Duc, Ha Anh', 'Hanvoravongchai, Piya', 'Lim, Jeremy', 'Lucero-Prisno, Don Eliseo', 'Ng, Nawi', 'Phaholyothin, Natalie', 'Phonvisay, Alay', 'Soe, Kyaw Min', 'Sychareun, Vanphanom']",Glob Health Action,,,True
5bcd3c424887a848429ff1027ac2aacf50944fbf,PMC,"Multiple functions of DDX3 RNA helicase in gene regulation, tumorigenesis, and viral infection",http://dx.doi.org/10.3389/fgene.2014.00423,PMC4257086,25538732,CC BY,"The DEAD-box RNA helicase DDX3 is a multifunctional protein involved in all aspects of RNA metabolism, including transcription, splicing, mRNA nuclear export, translation, RNA decay and ribosome biogenesis. In addition, DDX3 is also implicated in cell cycle regulation, apoptosis, Wnt-β-catenin signaling, tumorigenesis, and viral infection. Notably, recent studies suggest that DDX3 is a component of anti-viral innate immune signaling pathways. Indeed, DDX3 contributes to enhance the induction of anti-viral mediators, interferon (IFN) regulatory factor 3 and type I IFN. However, DDX3 seems to be an important target for several viruses, such as human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV), hepatitis B virus (HBV), and poxvirus. DDX3 interacts with HIV-1 Rev or HCV Core protein and modulates its function. At least, DDX3 is required for both HIV-1 and HCV replication. Therefore, DDX3 could be a novel therapeutic target for the development of drug against HIV-1 and HCV.",2014 Dec 5,"Ariumi, Yasuo",Front Genet,,,True
be314554a535360c674f8666efdefd43e38e5ccc,PMC,Molecular detection and genotypic characterization of Toxoplasma gondii infection in bats in four provinces of China,http://dx.doi.org/10.1186/s13071-014-0558-7,PMC4258805,25465220,CC BY,"BACKGROUND: Toxoplasma gondii is an intracellular protozoan parasite that infects a wide variety of warm-blooded hosts, including humans. Limited information about T. gondii infection in bats is available in China. The objective of the present study was to determine prevalence and genetic characterization of T. gondii infection in bats in Jilin, Liaoning, Jiangxi and Guangdong provinces, China. METHODS: During May 2005 to August 2013, bats were sampled from Jilin, Liaoning, Jiangxi, and Guangdong provinces, China, and liver tissues were collected for the detection of T. gondii by a nested PCR targeting the B1 gene. The positive samples were genotyped at 11 genetic markers (SAG1, 5′-and 3′-SAG2, alternative SAG2, SAG3, BTUB, GRA6, L358, PK1, c22-8, c29-2, and Apico) using multilocus polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: A total of 626 bats representing 10 species were examined for T. gondii infection, 38 (6.1%) were tested positive with by PCR, 8 positive DNA samples were completely genotyped, of which 3 samples (2 from Cynopterus sphinx, and 1 from Murina leucogaster) represented ToxoDB#10, and 5 samples (2 from Murina leucogaster, 2 from Myotis chinensis, and 1 from Rhinolophus ferrumequinum) belonged to ToxoDB#9 (http://toxodb.org/toxo/). CONCLUSIONS: The present study revealed an overall T. gondii prevalence of 6.1% in bats from Jilin, Liaoning, Jiangxi and Guangdong provinces in China, and reported two T. gondii genotypes (ToxoDB#9 and #10) having a wide geographical distribution in China. These results provide new genetic information about T. gondii infection in bats, and have implications for better understanding of the genetic diversity of T. gondii in China and elsewhere.",2014 Dec 3,"['Qin, Si-Yuan', 'Cong, Wei', 'Liu, Ye', 'Li, Nan', 'Wang, Ze-Dong', 'Zhang, Fu-Kai', 'Huang, Si-Yang', 'Zhu, Xing-Quan', 'Liu, Quan']",Parasit Vectors,,,True
90b1c08620b3bcc5694e31a241e2be2589003030,PMC,Clostridium difficile carriage in hospitalized cancer patients: a prospective investigation in eastern China,http://dx.doi.org/10.1186/1471-2334-14-523,PMC4261591,25267108,CC BY,"BACKGROUND: Clostridium difficile carriage has been considered as a potential source for the deadly infection, but its role in cancer patients is still unclear. We aimed to identify the clinical and immunological factors that are related to C. difficile carriage in Chinese cancer patients. METHODS: A total of 400 stool samples were collected from cancer patients who received chemotherapy in three hospitals of eastern China. Bacterial genomic DNA was extracted and two toxin genes (tcdA and tcdB) were detected. PCR ribotyping was performed using capillary gel electrophoresis. Concentrations of prostaglandin E2 (PGE2), transforming growth factor beta (TGF-β) and interleukin-10 (IL-10) were measured using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Eighty-two (20.5%) samples were confirmed to be C. difficile-positive and positive for tpi, tcdA, and tcdB genes. The C. difficile-positive rates in patients with diarrhea and no diarrhea were 35% and 19.7%, respectively (p = 0.09). Patients who were younger than 50 years old and were hospitalized for at least 10 days had a C. difficile-positive rate as high as 35%. In contrast, patients who were older than 50 years old and were hospitalized for less than 10 days had a C. difficile-positive rate of only 12.7% (p = 0.0009). No association was found between C. difficile carriage and chemotherapy regimen, antibiotic drug use, or immunosuppressive mediators, such as prostaglandin E2 (PGE2), transforming growth factor beta (TGF-β), or interleukin-10 (IL-10). Twelve ribotypes of C. difficile were identified, but none of them belonged to ribotype 027. CONCLUSIONS: We conclude that younger patients and those with longer hospitalization stays may be more prone to C. difficile carriage. Studies of larger populations are warranted to clarify the exact role of C. difficile carriage in hospitalized cancer patients in China. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-523) contains supplementary material, which is available to authorized users.",2014 Sep 29,"['Fang, Wei-Jia', 'Jing, Da-Zhi', 'Luo, Yun', 'Fu, Cai-Yun', 'Zhao, Peng', 'Qian, Jiong', 'Tian, Bing-Ru', 'Chen, Xiao-Gang', 'Zheng, Yu-Long', 'Zheng, Yi', 'Deng, Jing', 'Zou, Wei-Hua', 'Feng, Xue-Ren', 'Liu, Fan-Long', 'Mou, Xiao-Zhou', 'Zheng, Shu-Sen']",BMC Infect Dis,,,True
20c5f4025a94ca3a48d6d8a23a9db2ebc8b5ec03,PMC,Lactate dehydrogenase and caspase activity in nasopharyngeal secretions are predictors of bronchiolitis severity,http://dx.doi.org/10.1111/irv.12276,PMC4262276,25132512,CC BY,"BACKGROUND: Bronchiolitis is the leading cause of hospitalization in infants. Biomarkers of disease severity might help in clinical management. OBJECTIVE: To determine the clinical predictiveness of NW-LDH, NW-caspase 3/7, and NW-LDH/NW-caspase 3/7 ratio in bronchiolitis. METHODS: Previously healthy children less than 24 months of age with bronchiolitis were recruited from the Texas Children's emergency room and intensive care unit from October 2010 to April 2011. Demographic, clinical information, and NW samples were obtained at enrollment. NW samples were analyzed for respiratory viruses, caspase 3/7, and LDH. RESULTS: A viral pathogen was detected in 91·6% of 131 children, with the most common being respiratory syncytial virus and human rhinovirus. A single infection was found in 61·8% of subjects and co-infection in 29·8%. Children admitted to ICU had significantly higher NW-LDH than children sent home from the ER or admitted to the general floor (P = 0·02). Children infected with RSV had the highest NW-LDH concentration (P = 0·03) compared with other viral infections. NW-LDH and NW-caspase were significantly correlated (r = 0·77, P < 0·0001). The univariate models showed NW-LDH and NW-LDH/NW- caspase 3/7 ratio were directly associated with hospitalization. Mutivariate regression analyses suggested a complex interaction between the biomarkers, demographics, and disposition. CONCLUSIONS: NW-LDH, NW-caspase 3/7 and NW-LDH/NW-caspase 3/7 ratio and their interactions with demographic factors are predictive of bronchiolitis severity and can help distinguish children requiring ICU-level care from those admitted to the general floor, or discharged home from the emergency center.",2014 Nov 12,"['Mehta, Reena', 'Scheffler, Margaret', 'Tapia, Lorena', 'Aideyan, Letisha', 'Patel, Kirtida D', 'Jewell, Alan M', 'Avadhanula, Vasanthi', 'Mei, Minghua', 'Garofalo, Roberto P', 'Piedra, Pedro A']",Influenza Other Respir Viruses,,,True
d100ca657bd37c9878a08f7fcc3a9b8ad2d1830f,PMC,Population-based hospitalization incidence of respiratory viruses in community-acquired pneumonia in children younger than 5 years of age,http://dx.doi.org/10.1111/irv.12277,PMC4262277,25185835,CC BY,,2014 Nov 3,"['Chiu, Susan S', 'Ho, Pak-Leung', 'Peiris, Malik J S', 'Chan, Kwok Hung', 'Chan, Eunice L Y']",Influenza Other Respir Viruses,,,True
d494b68c054d6058bce92529a6d9ef3f7302094f,PMC,Insights into potential pathogenesis mechanisms associated with Campylobacter jejuni-induced abortion in ewes,http://dx.doi.org/10.1186/s12917-014-0274-8,PMC4262353,25420712,CC BY,"BACKGROUND: Campylobacter jejuni is commonly found in the gastrointestinal tract of many food-animals including sheep without causing visible clinical symptoms of disease. However, C. jejuni has been implicated in ovine abortion cases worldwide. Specifically, in the USA, the C. jejuni sheep abortion (SA) clone has been increasingly associated with sheep abortion. In vivo studies in sheep (the natural host) are needed to better characterize the virulence potential and pathogenesis of this clone. RESULTS: Pregnant ewes intravenously (IV) or orally inoculated with ovine or bovine abortion-associated C. jejuni SA clones exhibited partial or complete uterine prolapse with retained placenta, and abortion or stillbirth, whereas delivery of healthy lambs occurred in pregnant ewes inoculated with C. jejuni 81–176 or in the uninfected group. In sheep inoculated with the SA clone, histopathological lesions including suppurative necrotizing placentitis and/or endometritis coincided with: 1) increased apoptotic death of trophoblasts, 2) increased expression of the host genes (e.g. genes encoding interleukin IL-6 and IL-15) related to cellular necrosis and pro-inflammatory responses in uterus, and 3) decreased expression of the genes encoding GATA binding protein 6, chordin, and insulin-like 3 (INSL3) that account for embryonic development in uterus. Immunohistochemistry revealed localization of bacterial antigens in trophoblasts lining the chorioallantoic membrane of ewes inoculated with the C. jejuni SA clone. CONCLUSIONS: The results showed that C. jejuni SA clones are capable of causing abortion or stillbirth in experimentally infected sheep. Furthermore, down- or up-regulation of specific genes in the uterus of infected pregnant ewes might implicate host genes in facilitating the disease progression. Since the C. jejuni SA strains share genotypic similarities with clones that have been isolated from human clinical cases of gastroenteritis, these strains might represent a potential public health risk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-014-0274-8) contains supplementary material, which is available to authorized users.",2014 Nov 25,"['Sanad, Yasser M', 'Jung, Kwonil', 'Kashoma, Isaac', 'Zhang, Xiaoli', 'Kassem, Issmat I', 'Saif, Yehia M', 'Rajashekara, Gireesh']",BMC Vet Res,,,True
3a8f3c3b8c4be0144795e7dc34472a9a7dd35cc5,PMC,Insights into potential pathogenesis mechanisms associated with Campylobacter jejuni-induced abortion in ewes,http://dx.doi.org/10.1186/s12917-014-0274-8,PMC4262353,25420712,CC BY,"BACKGROUND: Campylobacter jejuni is commonly found in the gastrointestinal tract of many food-animals including sheep without causing visible clinical symptoms of disease. However, C. jejuni has been implicated in ovine abortion cases worldwide. Specifically, in the USA, the C. jejuni sheep abortion (SA) clone has been increasingly associated with sheep abortion. In vivo studies in sheep (the natural host) are needed to better characterize the virulence potential and pathogenesis of this clone. RESULTS: Pregnant ewes intravenously (IV) or orally inoculated with ovine or bovine abortion-associated C. jejuni SA clones exhibited partial or complete uterine prolapse with retained placenta, and abortion or stillbirth, whereas delivery of healthy lambs occurred in pregnant ewes inoculated with C. jejuni 81–176 or in the uninfected group. In sheep inoculated with the SA clone, histopathological lesions including suppurative necrotizing placentitis and/or endometritis coincided with: 1) increased apoptotic death of trophoblasts, 2) increased expression of the host genes (e.g. genes encoding interleukin IL-6 and IL-15) related to cellular necrosis and pro-inflammatory responses in uterus, and 3) decreased expression of the genes encoding GATA binding protein 6, chordin, and insulin-like 3 (INSL3) that account for embryonic development in uterus. Immunohistochemistry revealed localization of bacterial antigens in trophoblasts lining the chorioallantoic membrane of ewes inoculated with the C. jejuni SA clone. CONCLUSIONS: The results showed that C. jejuni SA clones are capable of causing abortion or stillbirth in experimentally infected sheep. Furthermore, down- or up-regulation of specific genes in the uterus of infected pregnant ewes might implicate host genes in facilitating the disease progression. Since the C. jejuni SA strains share genotypic similarities with clones that have been isolated from human clinical cases of gastroenteritis, these strains might represent a potential public health risk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-014-0274-8) contains supplementary material, which is available to authorized users.",2014 Nov 25,"['Sanad, Yasser M', 'Jung, Kwonil', 'Kashoma, Isaac', 'Zhang, Xiaoli', 'Kassem, Issmat I', 'Saif, Yehia M', 'Rajashekara, Gireesh']",BMC Vet Res,,,True
f4ff5cb594614337119fc4d7e39600c41119f80b,PMC,Microbial sequencing to improve individual and population health,http://dx.doi.org/10.1186/s13073-014-0103-5,PMC4262389,25505493,CC BY,Recent advances in sequencing technologies are changing the face of infectious disease investigation and control. Personalized anti-infective therapies and surveillance of emergent pathogen outbreaks are just two examples of the potential benefits of merging the fields of genomics and infectious diseases.,2014 Nov 19,"['Peacock, Sharon J', 'Weinstock, George M']",Genome Med,,,True
6525c7e5a16bc1ecd8fcdfda2cc6c82fe89c85c8,PMC,The Genome Landscape of the African Green Monkey Kidney-Derived Vero Cell Line,http://dx.doi.org/10.1093/dnares/dsu029,PMC4263300,25267831,CC BY,"Continuous cell lines that originate from mammalian tissues serve as not only invaluable tools for life sciences, but also important animal cell substrates for the production of various types of biological pharmaceuticals. Vero cells are susceptible to various types of microbes and toxins and have widely contributed to not only microbiology, but also the production of vaccines for human use. We here showed the genome landscape of a Vero cell line, in which 25,877 putative protein-coding genes were identified in the 2.97-Gb genome sequence. A homozygous ∼9-Mb deletion on chromosome 12 caused the loss of the type I interferon gene cluster and cyclin-dependent kinase inhibitor genes in Vero cells. In addition, an ∼59-Mb loss of heterozygosity around this deleted region suggested that the homozygosity of the deletion was established by a large-scale conversion. Moreover, a genomic analysis of Vero cells revealed a female Chlorocebus sabaeus origin and proviral variations of the endogenous simian type D retrovirus. These results revealed the genomic basis for the non-tumourigenic permanent Vero cell lineage susceptible to various pathogens and will be useful for generating new sub-lines and developing new tools in the quality control of Vero cells.",2014 Dec 28,"['Osada, Naoki', 'Kohara, Arihiro', 'Yamaji, Toshiyuki', 'Hirayama, Noriko', 'Kasai, Fumio', 'Sekizuka, Tsuyoshi', 'Kuroda, Makoto', 'Hanada, Kentaro']",DNA Res,,,True
4a87f2bdd6553f6be3c6f415b16e1e152633d46b,PMC,The Genome Landscape of the African Green Monkey Kidney-Derived Vero Cell Line,http://dx.doi.org/10.1093/dnares/dsu029,PMC4263300,25267831,CC BY,"Continuous cell lines that originate from mammalian tissues serve as not only invaluable tools for life sciences, but also important animal cell substrates for the production of various types of biological pharmaceuticals. Vero cells are susceptible to various types of microbes and toxins and have widely contributed to not only microbiology, but also the production of vaccines for human use. We here showed the genome landscape of a Vero cell line, in which 25,877 putative protein-coding genes were identified in the 2.97-Gb genome sequence. A homozygous ∼9-Mb deletion on chromosome 12 caused the loss of the type I interferon gene cluster and cyclin-dependent kinase inhibitor genes in Vero cells. In addition, an ∼59-Mb loss of heterozygosity around this deleted region suggested that the homozygosity of the deletion was established by a large-scale conversion. Moreover, a genomic analysis of Vero cells revealed a female Chlorocebus sabaeus origin and proviral variations of the endogenous simian type D retrovirus. These results revealed the genomic basis for the non-tumourigenic permanent Vero cell lineage susceptible to various pathogens and will be useful for generating new sub-lines and developing new tools in the quality control of Vero cells.",2014 Dec 28,"['Osada, Naoki', 'Kohara, Arihiro', 'Yamaji, Toshiyuki', 'Hirayama, Noriko', 'Kasai, Fumio', 'Sekizuka, Tsuyoshi', 'Kuroda, Makoto', 'Hanada, Kentaro']",DNA Res,,,False
1624c6455f4fb4a8e871403b0e27a217bcdc83b2,PMC,Isothermal Amplification Methods for the Detection of Nucleic Acids in Microfluidic Devices,http://dx.doi.org/10.3390/bios3010018,PMC4263587,25587397,CC BY,"Diagnostic tools for biomolecular detection need to fulfill specific requirements in terms of sensitivity, selectivity and high-throughput in order to widen their applicability and to minimize the cost of the assay. The nucleic acid amplification is a key step in DNA detection assays. It contributes to improving the assay sensitivity by enabling the detection of a limited number of target molecules. The use of microfluidic devices to miniaturize amplification protocols reduces the required sample volume and the analysis times and offers new possibilities for the process automation and integration in one single device. The vast majority of miniaturized systems for nucleic acid analysis exploit the polymerase chain reaction (PCR) amplification method, which requires repeated cycles of three or two temperature-dependent steps during the amplification of the nucleic acid target sequence. In contrast, low temperature isothermal amplification methods have no need for thermal cycling thus requiring simplified microfluidic device features. Here, the use of miniaturized analysis systems using isothermal amplification reactions for the nucleic acid amplification will be discussed.",2012 Dec 27,"['Zanoli, Laura Maria', 'Spoto, Giuseppe']",Biosensors (Basel),,,True
fa5e90f78c7365ea9ad6b8b9cf9b6e43a1ca727c,PMC,"3D QSAR Studies, Pharmacophore Modeling and Virtual Screening on a Series of Steroidal Aromatase Inhibitors",http://dx.doi.org/10.3390/ijms151120927,PMC4264204,25405729,CC BY,"Aromatase inhibitors are the most important targets in treatment of estrogen-dependent cancers. In order to search for potent steroidal aromatase inhibitors (SAIs) with lower side effects and overcome cellular resistance, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of SAIs to build 3D QSAR models. The reliable and predictive CoMFA and CoMSIA models were obtained with statistical results (CoMFA: q(2) = 0.636, r(2)(ncv) = 0.988, r(2)(pred) = 0.658; CoMSIA: q(2) = 0.843, r(2)(ncv) = 0.989, r(2)(pred) = 0.601). This 3D QSAR approach provides significant insights that can be used to develop novel and potent SAIs. In addition, Genetic algorithm with linear assignment of hypermolecular alignment of database (GALAHAD) was used to derive 3D pharmacophore models. The selected pharmacophore model contains two acceptor atoms and four hydrophobic centers, which was used as a 3D query for virtual screening against NCI2000 database. Six hit compounds were obtained and their biological activities were further predicted by the CoMFA and CoMSIA models, which are expected to design potent and novel SAIs.",2014 Nov 14,"['Xie, Huiding', 'Qiu, Kaixiong', 'Xie, Xiaoguang']",Int J Mol Sci,,,True
26ba0cb6190e2a4b476ebf7122a0e439bbe80229,PMC,"MicroRNA miR-320a and miR-140 inhibit mink enteritis virus infection by repression of its receptor, feline transferrin receptor",http://dx.doi.org/10.1186/s12985-014-0210-3,PMC4264318,25465595,CC BY,"Mink enteritis virus (MEV) is one of the most important pathogens in the mink industry. Recent studies have shed light into the role of microRNAs (miRNAs), small noncoding RNAs of length ranging from 18–23 nucleotides (nt), as critical modulators in the host-pathogen interaction networks. We previously showed that miRNA miR-181b can inhibit MEV replication by repression of viral non-structural protein 1 expression. Here, we report that two other miRNAs (miR-320a and miR-140) inhibit MEV entry into feline kidney (F81) cells by downregulating its receptor, transferrin receptor (TfR), by targeting the 3′ untranslated region (UTR) of TfR mRNA, while being themselves upregulated.",2014 Dec 3,"['Sun, Jia-zeng', 'Wang, Jigui', 'Wang, Shuang', 'Yuan, Daoli', 'Li, Zhili', 'Yi, Bao', 'Hou, Qiang', 'Mao, Yaping', 'Liu, Weiquan']",Virol J,,,True
3849786c8c14c11ae4b19b4543672421e5d169fd,PMC,Plant-based vaccines against viruses,http://dx.doi.org/10.1186/s12985-014-0205-0,PMC4264547,25465382,CC BY,"Plant-made or “biofarmed” viral vaccines are some of the earliest products of the technology of plant molecular farming, and remain some of the brightest prospects for the success of this field. Proofs of principle and of efficacy exist for many candidate viral veterinary vaccines; the use of plant-made viral antigens and of monoclonal antibodies for therapy of animal and even human viral disease is also well established. This review explores some of the more prominent recent advances in the biofarming of viral vaccines and therapies, including the recent use of ZMapp for Ebolavirus infection, and explores some possible future applications of the technology.",2014 Dec 3,"Rybicki, Edward P",Virol J,,,True
bbe74d62d65366418b61cb33a4ffe5ffcd3a8fce,PMC,"Characterization of a novel orthoreovirus isolated from fruit bat, China",http://dx.doi.org/10.1186/s12866-014-0293-4,PMC4264558,25433675,CC BY,"BACKGROUND: In recent years novel human respiratory disease agents have been described for Southeast Asia and Australia. The causative pathogens were classified as pteropine orthoreoviruses with a strong phylogenetic relationship to orthoreoviruses of bat origin. RESULTS: In this report, we isolated a novel Melaka-like reovirus (named “Cangyuan virus”) from intestinal content samples of one fruit bat residing in China’s Yunnan province. Phylogenetic analysis of the whole Cangyuan virus genome sequences of segments L, M and S demonstrated the genetic diversity of the Cangyuan virus. In contrast to the L and M segments, the phylogenetic trees for the S segments of Cangyuan virus demonstrated a greater degree of heterogeneity. CONCLUSIONS: Phylogenetic analysis indicated that the Cangyuan virus was a novel orthoreovirus and substantially different from currently known members of Pteropine orthoreovirus (PRV) species group. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12866-014-0293-4) contains supplementary material, which is available to authorized users.",2014 Nov 30,"['Hu, Tingsong', 'Qiu, Wei', 'He, Biao', 'Zhang, Yan', 'Yu, Jing', 'Liang, Xiu', 'Zhang, Wendong', 'Chen, Gang', 'Zhang, Yingguo', 'Wang, Yiyin', 'Zheng, Ying', 'Feng, Ziliang', 'Hu, Yonghe', 'Zhou, Weiguo', 'Tu, Changchun', 'Fan, Quanshui', 'Zhang, Fuqiang']",BMC Microbiol,,,True
d2d1d6227304c56323303dc51509bf3217925dcb,PMC,Lipid interactions during virus entry and infection,http://dx.doi.org/10.1111/cmi.12340,PMC4265854,25131438,CC BY,"For entry and infection viruses have developed numerous strategies to subjugate indispensable cellular factors and functions. Host cell lipids and cellular lipid synthesis machinery are no exception. Not only do viruses exploit existing lipid signalling and modifications for virus entry and trafficking, they also reprogram lipid synthesis, metabolism, and compartmentalization for assembly and egress. Here we review these various concepts and highlight recent progress in understanding viral interactions with host cell lipids during entry and assembly.",2014 Sep 11,"['Mazzon, Michela', 'Mercer, Jason']",Cell Microbiol,,,True
fee63d10e8db56b72c9385149a4e57afa8500981,PMC,Polymorphisms in the feline TNFA and CD209 genes are associated with the outcome of feline coronavirus infection,http://dx.doi.org/10.1186/s13567-014-0123-6,PMC4267428,25512064,CC BY,"Feline infectious peritonitis (FIP), caused by feline coronavirus (FCoV) infection, is a highly lethal disease without effective therapy and prevention. With an immune-mediated disease entity, host genetic variant was suggested to influence the occurrence of FIP. This study aimed at evaluating cytokine-associated single nucleotide polymorphisms (SNPs), i.e., tumor necrosis factor alpha (TNF-α), receptor-associated SNPs, i.e., C-type lectin DC-SIGN (CD209), and the five FIP-associated SNPs identified from Birman cats of USA and Denmark origins and their associations with the outcome of FCoV infection in 71 FIP cats and 93 FCoV infected non-FIP cats in a genetically more diverse cat populations. A promoter variant, fTNFA - 421 T, was found to be a disease-resistance allele. One SNP was identified in the extracellular domain (ECD) of fCD209 at position +1900, a G to A substitution, and the A allele was associated with FIP susceptibility. Three SNPs located in the introns of fCD209, at positions +2276, +2392, and +2713, were identified to be associated with the outcome of FCoV infection, with statistical relevance. In contrast, among the five Birman FIP cat-associated SNPs, no genotype or allele showed significant differences between our FIP and non-FIP groups. As disease resistance is multifactorial and several other host genes could involve in the development of FIP, the five genetic traits identified in this study should facilitate in the future breeding of the disease-resistant animal to reduce the occurrence of cats succumbing to FIP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-014-0123-6) contains supplementary material, which is available to authorized users.",2014 Dec 16,"['Wang, Ying-Ting', 'Hsieh, Li-En', 'Dai, Yu-Rou', 'Chueh, Ling-Ling']",Vet Res,,,True
d9367d8e090900c57b11a99848144bd83dcb80bb,PMC,ApoD Mediates Binding of HDL to LDL and to Growing T24 Carcinoma,http://dx.doi.org/10.1371/journal.pone.0115180,PMC4267786,25513803,CC BY,"Apolipoprotein (Apo) D is an important protein produced in many parts of the body. It is necessary for the development and repair of the brain and protection from oxidative stress. The purpose of this study was to investigate the extent to which apoD interacts with lipoproteins in human plasma. By using detergent-free ELISA, we show that immobilized monoclonal antibodies against apoD very efficiently bind to low density lipoprotein (LDL) from plasma; this binding is as equally efficient as binding to an anti-apoB monoclonal antibody. Adding detergent to the plasma inhibited the binding, suggesting that the binding is dependent on the presence of intact lipoprotein particles. Reversing the system by using immobilized anti-apoB revealed that the affinity of apoD for LDL is rather low, suggesting that multiple bindings are needed for a durable connection. Biosensor experiments using purified lipoproteins also showed that purified apoD and high density lipoprotein 3 (HDL3), a lipoprotein fraction rich in apoD, were both able to bind LDL very efficiently, indicating that the HDL3-LDL interaction may be a physiological consequence of the affinity of apoD for LDL. Furthermore, we found that apoD increases the binding of HDL to actively growing T24 bladder carcinoma cells but not to quiescent, contact-inhibited, confluent T24 cells. This result is especially intriguing given that the T24 supernatant only contained detectable levels of apoD after growth inhibition, raising the possibility that alternating the expression of apoD and a putative apoD-receptor could give direction to the flow of lipids. In the current paper, we conclude that apoD mediates binding of HDL to LDL and to growing T24 carcinomas, thereby highlighting the importance of apoD in lipid metabolism.",2014 Dec 16,"['Braesch-Andersen, Sten', 'Beckman, Lena', 'Paulie, Staffan', 'Kumagai-Braesch, Makiko']",PLoS One,,,True
d51ce457ef5e113a0dfbd40dfb57e438e7d458ef,PMC,Proteomics informed by transcriptomics reveals Hendra virus sensitizes bat cells to TRAIL-mediated apoptosis,http://dx.doi.org/10.1186/s13059-014-0532-x,PMC4269970,25398248,CC BY,"BACKGROUND: Bats are a major reservoir of emerging infectious viruses. Many of these viruses are highly pathogenic to humans however bats remain asymptomatic. The mechanism by which bats control viral replication is unknown. Here we utilize an integrated approach of proteomics informed by transcriptomics to compare the response of immortalized bat and human cells following infection with the highly pathogenic bat-borne Hendra virus (HeV). RESULTS: The host response between the cell lines was significantly different at both the mRNA and protein levels. Human cells demonstrated minimal response eight hours post infection, followed by a global suppression of mRNA and protein abundance. Bat cells demonstrated a robust immune response eight hours post infection, which led to the up-regulation of apoptosis pathways, mediated through the tumor necrosis factor-related apoptosis inducing ligand (TRAIL). HeV sensitized bat cells to TRAIL-mediated apoptosis, by up-regulating death receptor transcripts. At 48 and 72 hours post infection, bat cells demonstrated a significant increase in apoptotic cell death. CONCLUSIONS: This is the first study to comprehensively compare the response of bat and human cells to a highly pathogenic zoonotic virus. An early induction of innate immune processes followed by apoptosis of virally infected bat cells highlights the possible involvement of programmed cell death in the host response. Our study shows for the first time a side-by-side high-throughput analysis of a dangerous zoonotic virus in cell lines derived from humans and the natural bat host. This enables a way to search for divergent mechanisms at a molecular level that may influence host pathogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0532-x) contains supplementary material, which is available to authorized users.",2014 Nov 15,"['Wynne, James W', 'Shiell, Brian J', 'Marsh, Glenn A', 'Boyd, Victoria', 'Harper, Jennifer A', 'Heesom, Kate', 'Monaghan, Paul', 'Zhou, Peng', 'Payne, Jean', 'Klein, Reuben', 'Todd, Shawn', 'Mok, Lawrence', 'Green, Diane', 'Bingham, John', 'Tachedjian, Mary', 'Baker, Michelle L', 'Matthews, David', 'Wang, Lin-Fa']",Genome Biol,,,False
f00106cad50635bb15409ac6039b93b5af031565,PMC,Proteomics informed by transcriptomics reveals Hendra virus sensitizes bat cells to TRAIL-mediated apoptosis,http://dx.doi.org/10.1186/s13059-014-0532-x,PMC4269970,25398248,CC BY,"BACKGROUND: Bats are a major reservoir of emerging infectious viruses. Many of these viruses are highly pathogenic to humans however bats remain asymptomatic. The mechanism by which bats control viral replication is unknown. Here we utilize an integrated approach of proteomics informed by transcriptomics to compare the response of immortalized bat and human cells following infection with the highly pathogenic bat-borne Hendra virus (HeV). RESULTS: The host response between the cell lines was significantly different at both the mRNA and protein levels. Human cells demonstrated minimal response eight hours post infection, followed by a global suppression of mRNA and protein abundance. Bat cells demonstrated a robust immune response eight hours post infection, which led to the up-regulation of apoptosis pathways, mediated through the tumor necrosis factor-related apoptosis inducing ligand (TRAIL). HeV sensitized bat cells to TRAIL-mediated apoptosis, by up-regulating death receptor transcripts. At 48 and 72 hours post infection, bat cells demonstrated a significant increase in apoptotic cell death. CONCLUSIONS: This is the first study to comprehensively compare the response of bat and human cells to a highly pathogenic zoonotic virus. An early induction of innate immune processes followed by apoptosis of virally infected bat cells highlights the possible involvement of programmed cell death in the host response. Our study shows for the first time a side-by-side high-throughput analysis of a dangerous zoonotic virus in cell lines derived from humans and the natural bat host. This enables a way to search for divergent mechanisms at a molecular level that may influence host pathogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0532-x) contains supplementary material, which is available to authorized users.",2014 Nov 15,"['Wynne, James W', 'Shiell, Brian J', 'Marsh, Glenn A', 'Boyd, Victoria', 'Harper, Jennifer A', 'Heesom, Kate', 'Monaghan, Paul', 'Zhou, Peng', 'Payne, Jean', 'Klein, Reuben', 'Todd, Shawn', 'Mok, Lawrence', 'Green, Diane', 'Bingham, John', 'Tachedjian, Mary', 'Baker, Michelle L', 'Matthews, David', 'Wang, Lin-Fa']",Genome Biol,,,True
4600273935786871df51c3644a39d86c3ad2cc8e,PMC,Assembly of viral genomes from metagenomes,http://dx.doi.org/10.3389/fmicb.2014.00714,PMC4270193,25566226,CC BY,"Viral infections remain a serious global health issue. Metagenomic approaches are increasingly used in the detection of novel viral pathogens but also to generate complete genomes of uncultivated viruses. In silico identification of complete viral genomes from sequence data would allow rapid phylogenetic characterization of these new viruses. Often, however, complete viral genomes are not recovered, but rather several distinct contigs derived from a single entity are, some of which have no sequence homology to any known proteins. De novo assembly of single viruses from a metagenome is challenging, not only because of the lack of a reference genome, but also because of intrapopulation variation and uneven or insufficient coverage. Here we explored different assembly algorithms, remote homology searches, genome-specific sequence motifs, k-mer frequency ranking, and coverage profile binning to detect and obtain viral target genomes from metagenomes. All methods were tested on 454-generated sequencing datasets containing three recently described RNA viruses with a relatively large genome which were divergent to previously known viruses from the viral families Rhabdoviridae and Coronaviridae. Depending on specific characteristics of the target virus and the metagenomic community, different assembly and in silico gap closure strategies were successful in obtaining near complete viral genomes.",2014 Dec 18,"['Smits, Saskia L.', 'Bodewes, Rogier', 'Ruiz-Gonzalez, Aritz', 'Baumgärtner, Wolfgang', 'Koopmans, Marion P.', 'Osterhaus, Albert D. M. E.', 'Schürch, Anita C.']",Front Microbiol,,,True
06b3f93a98def37bdbfa4487060cd836fdf1070d,PMC,Platelets and Infection – An Emerging Role of Platelets in Viral Infection,http://dx.doi.org/10.3389/fimmu.2014.00649,PMC4270245,25566260,CC BY,"Platelets are anucleate blood cells that play a crucial role in the maintenance of hemostasis. While platelet activation and elevated platelet counts (thrombocytosis) are associated with increased risk of thrombotic complications, low platelet counts (thrombocytopenia) and several platelet function disorders increase the risk of bleeding. Over the last years, more and more evidence has emerged that platelets and their activation state can also modulate innate and adaptive immune responses and low platelet counts have been identified as a surrogate marker for poor prognosis in septic patients. Viral infections often coincide with platelet activation. Host inflammatory responses result in the release of platelet activating mediators and a pro-oxidative and pro-coagulant environment, which favors platelet activation. However, viruses can also directly interact with platelets and megakaryocytes and modulate their function. Furthermore, platelets can be activated by viral antigen–antibody complexes and in response to some viruses B-lymphocytes also generate anti-platelet antibodies. All these processes contributing to platelet activation result in increased platelet consumption and removal and often lead to thrombocytopenia, which is frequently observed during viral infection. However, virus-induced platelet activation does not only modulate platelet count but also shape immune responses. Platelets and their released products have been reported to directly and indirectly suppress infection and to support virus persistence in response to certain viruses, making platelets a double-edged sword during viral infections. This review aims to summarize the current knowledge on platelet interaction with different types of viruses, the viral impact on platelet activation, and platelet-mediated modulations of innate and adaptive immune responses.",2014 Dec 18,"Assinger, Alice",Front Immunol,,,True
6e30b6ac327ca9f75d9f409d2c0884144569e414,PMC,Genome Sequence of Torovirus Identified from a Pig with Porcine Epidemic Diarrhea Virus from the United States,http://dx.doi.org/10.1128/genomeA.01291-14,PMC4271157,25523767,CC BY,"Porcine torovirus (PToV) strain PToV-NPL/2013 was identified from a pig that tested positive for porcine epidemic diarrhea virus (PEDV). The spike protein-encoding gene from PToV-NPL/2013 had 92% identity with PToV-SH1, suggesting that PToV circulating in the United States is slightly different from the isolates circulating in China. To our knowledge, this is the first report of PToV in the United States.",2014 Dec 18,"['Anbalagan, Srivishnupriya', 'Peterson, Jessica', 'Wassman, Brent', 'Elston, Josh', 'Schwartz, Karen']",Genome Announc,,,True
d71c2fa8fe1c3df75d031c50267993ede529b85c,PMC,The SARS coronavirus papain like protease can inhibit IRF3 at a post activation step that requires deubiquitination activity,http://dx.doi.org/10.1186/s12985-014-0209-9,PMC4272517,25481026,CC BY,"BACKGROUND: The outcome of a viral infection is regulated by complex interactions of viral and host factors. SARS coronavirus (SARS-CoV) engages and regulates several innate immune response pathways during infection. We have previously shown that the SARS-CoV Papain-like Protease (PLpro) inhibits type I interferon (IFN) by inhibiting IRF3 phosphorylation thereby blocking downstream Interferon induction. This finding prompted us to identify other potential mechanisms of inhibition of PLpro on IFN induction. METHODS: We have used plasmids expressing PLpro and IRF3 including an IRF3 mutant that is constitutively active, called IRF3(5D). In these experiments we utilize transfections, chromatin immunoprecipitation, Electro-mobility Shift Assays (EMSA) and protein localization to identify where IRF3 and IRF3(5D) are inhibited by PLpro. RESULTS: Here we show that PLpro also inhibits IRF3 activation at a step after phosphorylation and that this inhibition is dependent on the de-ubiquitination (DUB) activity of PLpro. We found that PLpro is able to block the type I IFN induction of a constitutively active IRF3, but does not inhibit IRF3 dimerization, nuclear localization or DNA binding. However, inhibition of PLpro’s DUB activity by mutagenesis blocked the IRF3 inhibition activity of PLpro, suggesting a role for IRF3 ubiquitination in induction of a type I IFN innate immune response. CONCLUSION: These results demonstrate an additional mechanism that PLpro is able to inhibit IRF3 signaling. These data suggest novel innate immune antagonism activities of PLpro that may contribute to SARS-CoV pathogenesis.",2014 Dec 7,"['Matthews, Krystal', 'Schäfer, Alexandra', 'Pham, Alissa', 'Frieman, Matthew']",Virol J,,,True
374861bab555d907099146fb05867d810fca1ad1,PMC,"Multicenter case–control study protocol of pneumonia etiology in children: Global Approach to Biological Research, Infectious diseases and Epidemics in Low-income countries (GABRIEL network)",http://dx.doi.org/10.1186/s12879-014-0635-8,PMC4272811,25927410,CC BY,"BACKGROUND: Data on the etiologies of pneumonia among children are inadequate, especially in developing countries. The principal objective is to undertake a multicenter incident case–control study of <5-year-old children hospitalized with pneumonia in developing and emerging countries, aiming to identify the causative agents involved in pneumonia while assessing individual and microbial factors associated with the risk of severe pneumonia. METHODS/DESIGN: A multicenter case–control study, based on the GABRIEL network, is ongoing. Ten study sites are located in 9 countries over 3 continents: Brazil, Cambodia, China, Haiti, India, Madagascar, Mali, Mongolia, and Paraguay. At least 1,000 incident cases and 1,000 controls will be enrolled and matched for age and date. Cases are hospitalized children <5 years with radiologically confirmed pneumonia, and the controls are children without any features suggestive of pneumonia. Respiratory specimens are collected from all enrolled subjects to identify 19 viruses and 5 bacteria. Whole blood from pneumonia cases is being tested for 3 major bacteria. S. pneumoniae-positive specimens are serotyped. Urine samples from cases only are tested for detection of antimicrobial activity. The association between procalcitonin, C-reactive protein and pathogens is being evaluated. A discovery platform will enable pathogen identification in undiagnosed samples. DISCUSSION: This multicenter study will provide descriptive results for better understanding of pathogens responsible for pneumonia among children in developing countries. The identification of determinants related to microorganisms associated with pneumonia and its severity should facilitate treatment and prevention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0635-8) contains supplementary material, which is available to authorized users.",2014 Dec 10,"['Picot, Valentina Sanchez', 'Bénet, Thomas', 'Messaoudi, Melina', 'Telles, Jean-Noël', 'Chou, Monidarin', 'Eap, Tekchheng', 'Wang, Jianwei', 'Shen, Kunling', 'Pape, Jean-William', 'Rouzier, Vanessa', 'Awasthi, Shally', 'Pandey, Nitin', 'Bavdekar, Ashish', 'Sanghvi, Sonali', 'Robinson, Annick', 'Contamin, Bénédicte', 'Hoffmann, Jonathan', 'Sylla, Maryam', 'Diallo, Souleymane', 'Nymadawa, Pagbajabyn', 'Dash-Yandag, Budragchaagiin', 'Russomando, Graciela', 'Basualdo, Wilma', 'Siqueira, Marilda M', 'Barreto, Patricia', 'Komurian-Pradel, Florence', 'Vernet, Guy', 'Endtz, Hubert', 'Vanhems, Philippe', 'Paranhos-Baccalà, Gláucia']",BMC Infect Dis,,,True
d018f86bb03f5462f6201a4a2b897df8e5564ca0,PMC,Pulmonary vascular dysfunction in ARDS,http://dx.doi.org/10.1186/s13613-014-0028-6,PMC4273697,25593744,CC BY,"Acute respiratory distress syndrome (ARDS) is characterised by diffuse alveolar damage and is frequently complicated by pulmonary hypertension (PH). Multiple factors may contribute to the development of PH in this setting. In this review, we report the results of a systematic search of the available peer-reviewed literature for papers that measured indices of pulmonary haemodynamics in patients with ARDS and reported on mortality in the period 1977 to 2010. There were marked differences between studies, with some reporting strong associations between elevated pulmonary arterial pressure or elevated pulmonary vascular resistance and mortality, whereas others found no such association. In order to discuss the potential reasons for these discrepancies, we review the physiological concepts underlying the measurement of pulmonary haemodynamics and highlight key differences between the concepts of resistance in the pulmonary and systemic circulations. We consider the factors that influence pulmonary arterial pressure, both in normal lungs and in the presence of ARDS, including the important effects of mechanical ventilation. Pulmonary arterial pressure, pulmonary vascular resistance and transpulmonary gradient (TPG) depend not alone on the intrinsic properties of the pulmonary vascular bed but are also strongly influenced by cardiac output, airway pressures and lung volumes. The great variability in management strategies within and between studies means that no unified analysis of these papers was possible. Uniquely, Bull et al. (Am J Respir Crit Care Med 182:1123–1128, 2010) have recently reported that elevated pulmonary vascular resistance (PVR) and TPG were independently associated with increased mortality in ARDS, in a large trial with protocol-defined management strategies and using lung-protective ventilation. We then considered the existing literature to determine whether the relationship between PVR/TPG and outcome might be causal. Although we could identify potential mechanisms for such a link, the existing evidence does not allow firm conclusions to be drawn. Nonetheless, abnormally elevated PVR/TPG may provide a useful index of disease severity and progression. Further studies are required to understand the role and importance of pulmonary vascular dysfunction in ARDS in the era of lung-protective ventilation.",2014 Aug 22,"['Ryan, Donal', 'Frohlich, Stephen', 'McLoughlin, Paul']",Ann Intensive Care,,,True
a1f20fd6adb16f74b5c4a7c0543c55e80e500e02,PMC,Do we need a replacement medication for influenza with good efficacy?,http://dx.doi.org/10.1186/s40199-014-0084-3,PMC4274729,25523212,CC BY,,2014 Dec 16,"['Arastoo, Mahmoud', 'Khorshid, Hamid Reza Khorram']",Daru,,,True
0f78cf5bc61d9cc158832a1c680d8aca449785dc,PMC,Clinical evaluation of viral acute respiratory tract infections in children presenting to the emergency department of a tertiary referral hospital in the Netherlands,http://dx.doi.org/10.1186/s12887-014-0297-0,PMC4276012,25491885,CC BY,"BACKGROUND: The relative incidence and clinical impact of individual respiratory viruses remains unclear among children presenting to the hospital emergency department with acute respiratory tract infection (ARTI). METHODS: During two winter periods, respiratory virus real-time multiplex PCR results were evaluated from children (< 18 years) presenting to the emergency department of a tertiary referral hospital with ARTI that had been sampled within 48 hours of hospital presentation. In an attempt to identify virus-specific distinguishing clinical features, single virus infections were correlated with presenting signs and symptoms, clinical findings and outcomes using multivariate logistic regression. RESULTS: In total, 274 children with ARTI were evaluated and most were aged < 3 years (236/274, 86%). PCR detected respiratory viruses in 224/274 (81.8%) children and included 162 (59%) single and 62 (23%) mixed virus infections. Respiratory syncytial virus (RSV) and human rhinovirus (HRV) single virus infections were common among children aged < 3 years, but proportional differences compared to older children were only significant for RSV (95% CI 1.3–15). Clinical differentiation between viral ARTIs was not possible due to common shared presenting signs and symptoms and the high frequency of mixed viral infections. We observed virus-associated outcome differences among children aged < 3 years. Oxygen treatment was associated with RSV (OR 3.6) and inversely correlated with FLU (OR 0.05). Treatment with steroids (OR 3.4) or bronchodilators (OR 3.4) was associated with HRV. Severe respiratory complications were associated with HRV (OR 3.5) and inversely correlated with RSV (OR 0.24). CONCLUSIONS: Respiratory viruses are frequently detected in young children presenting to the hospital emergency department with ARTI and require PCR diagnosis since presenting signs and symptoms are not discriminant for a type of virus. RSV and HRV bear a high burden of morbidity in the pediatric clinical setting.",2014 Dec 10,"['Gooskens, Jairo', 'van der Ploeg, Vishnu', 'Sukhai, Ram N', 'Vossen, Ann CTM', 'Claas, Eric CJ', 'Kroes, Aloys CM']",BMC Pediatr,,,True
75957355c6d3c199d42896dfcd2f0f168ef5d348,PMC,Detection of Influenza Virus Infection Using Two PCR Methods,http://dx.doi.org/10.1155/2014/274679,PMC4276355,25574169,CC BY,"Rapid, accurate, and cost-effective methods to identify the cause of respiratory tract infections are needed to maximize clinical benefit. Outpatients with acute respiratory illness were tested for influenza using a singleplex reverse transcriptase polymerase chain reaction (SRT-PCR) method. A multiplex RT-PCR (MRT-PCR) method tested for influenza and 17 other viruses and was compared with SRT-PCR using chi-square tests. Among 935 patients, 335 (36%) tested positive for influenza A and influenza B using SRT-PCR. Using MRT-PCR, 320 (34.2%) tested positive for influenza A and influenza B. This study supports MRT-PCR as a comparable method for detecting influenza among patients seeking outpatient care for acute respiratory illnesses.",2014 Dec 9,"['Zimmerman, Richard K.', 'Rinaldo, Charles R.', 'Nowalk, Mary Patricia', 'Balasubramani, G. K.', 'Thompson, Mark G.', 'Bullotta, Arlene', 'Susick, Michael', 'Wisniewski, Stephen']",Adv Virol,,,True
0b875918f93152038d3a87f24e51abc1fd99a348,PMC,Immunology of Bats and Their Viruses: Challenges and Opportunities,http://dx.doi.org/10.3390/v6124880,PMC4276934,25494448,CC BY,"Bats are reservoir hosts of several high-impact viruses that cause significant human diseases, including Nipah virus, Marburg virus and rabies virus. They also harbor many other viruses that are thought to have caused disease in humans after spillover into intermediate hosts, including SARS and MERS coronaviruses. As is usual with reservoir hosts, these viruses apparently cause little or no pathology in bats. Despite the importance of bats as reservoir hosts of zoonotic and potentially zoonotic agents, virtually nothing is known about the host/virus relationships; principally because few colonies of bats are available for experimental infections, a lack of reagents, methods and expertise for studying bat antiviral responses and immunology, and the difficulty of conducting meaningful field work. These challenges can be addressed, in part, with new technologies that are species-independent that can provide insight into the interactions of bats and viruses, which should clarify how the viruses persist in nature, and what risk factors might facilitate transmission to humans and livestock.",2014 Dec 8,"Schountz, Tony",Viruses,,,True
f6e6534cb423c1823ad38d7d5c0a98c303f2efdb,PMC,Architectural Insight into Inovirus-Associated Vectors (IAVs) and Development of IAV-Based Vaccines Inducing Humoral and Cellular Responses: Implications in HIV-1 Vaccines,http://dx.doi.org/10.3390/v6125047,PMC4276942,25525909,CC BY,"Inovirus-associated vectors (IAVs) are engineered, non-lytic, filamentous bacteriophages that are assembled primarily from thousands of copies of the major coat protein gp8 and just five copies of each of the four minor coat proteins gp3, gp6, gp7 and gp9. Inovirus display studies have shown that the architecture of inoviruses makes all coat proteins of the inoviral particle accessible to the outside. This particular feature of IAVs allows foreign antigenic peptides to be displayed on the outer surface of the virion fused to its coat proteins and for more than two decades has been exploited in many applications including antibody or peptide display libraries, drug design, and vaccine development against infectious and non-infectious diseases. As vaccine carriers, IAVs have been shown to elicit both a cellular and humoral response against various pathogens through the display of antibody epitopes on their coat proteins. Despite their high immunogenicity, the goal of developing an effective vaccine against HIV-1 has not yet materialized. One possible limitation of previous efforts was the use of broadly neutralizing antibodies, which exhibited autoreactivity properties. In the past five years, however, new, more potent broadly neutralizing antibodies that do not exhibit autoreactivity properties have been isolated from HIV-1 infected individuals, suggesting that vaccination strategies aimed at producing such broadly neutralizing antibodies may confer protection against infection. The utilization of these new, broadly neutralizing antibodies in combination with the architectural traits of IAVs have driven the current developments in the design of an inovirus-based vaccine against HIV-1. This article reviews the applications of IAVs in vaccine development, with particular emphasis on the design of inoviral-based vaccines against HIV-1.",2014 Dec 17,"['Hassapis, Kyriakos A.', 'Stylianou, Dora C.', 'Kostrikis, Leondios G.']",Viruses,,,True
06f33aa8d51ad1c6081cd855c8d274d47e1ee74e,PMC,Cytoplasmic Translocation of Polypyrimidine Tract-Binding Protein and Its Binding to Viral RNA during Japanese Encephalitis Virus Infection Inhibits Virus Replication,http://dx.doi.org/10.1371/journal.pone.0114931,PMC4278868,25545659,CC BY,"Japanese encephalitis virus (JEV) has a single-stranded, positive-sense RNA genome containing a single open reading frame flanked by the 5′- and 3′-non-coding regions (NCRs). The virus genome replicates via a negative-sense RNA intermediate. The NCRs and their complementary sequences in the negative-sense RNA are the sites for assembly of the RNA replicase complex thereby regulating the RNA synthesis and virus replication. In this study, we show that the 55-kDa polypyrimidine tract-binding protein (PTB) interacts in vitro with both the 5′-NCR of the positive-sense genomic RNA - 5NCR(+), and its complementary sequence in the negative-sense replication intermediate RNA - 3NCR(-). The interaction of viral RNA with PTB was validated in infected cells by JEV RNA co-immunoprecipitation and JEV RNA-PTB colocalization experiments. Interestingly, we observed phosphorylation-coupled translocation of nuclear PTB to cytoplasmic foci that co-localized with JEV RNA early during JEV infection. Our studies employing the PTB silencing and over-expression in cultured cells established an inhibitory role of PTB in JEV replication. Using RNA-protein binding assay we show that PTB competitively inhibits association of JEV 3NCR(-) RNA with viral RNA-dependent RNA polymerase (NS5 protein), an event required for the synthesis of the plus-sense genomic RNA. cAMP is known to promote the Protein kinase A (PKA)-mediated PTB phosphorylation. We show that cells treated with a cAMP analogue had an enhanced level of phosphorylated PTB in the cytoplasm and a significantly suppressed JEV replication. Data presented here show a novel, cAMP-induced, PTB-mediated, innate host response that could effectively suppress JEV replication in mammalian cells.",2014 Dec 29,"['Bhullar, Deepika', 'Jalodia, Richa', 'Kalia, Manjula', 'Vrati, Sudhanshu']",PLoS One,,,True
8134e0946079f5ef0bbbd7b65ce13657483b8160,PMC,Cullin E3 Ligases and Their Rewiring by Viral Factors,http://dx.doi.org/10.3390/biom4040897,PMC4279162,25314029,CC BY,"The ability of viruses to subvert host pathways is central in disease pathogenesis. Over the past decade, a critical role for the Ubiquitin Proteasome System (UPS) in counteracting host immune factors during viral infection has emerged. This counteraction is commonly achieved by the expression of viral proteins capable of sequestering host ubiquitin E3 ligases and their regulators. In particular, many viruses hijack members of the Cullin-RING E3 Ligase (CRL) family. Viruses interact in many ways with CRLs in order to impact their ligase activity; one key recurring interaction involves re-directing CRL complexes to degrade host targets that are otherwise not degraded within host cells. Removal of host immune factors by this mechanism creates a more amenable cellular environment for viral propagation. To date, a small number of target host factors have been identified, many of which are degraded via a CRL-proteasome pathway. Substantial effort within the field is ongoing to uncover the identities of further host proteins targeted in this fashion and the underlying mechanisms driving their turnover by the UPS. Elucidation of these targets and mechanisms will provide appealing anti-viral therapeutic opportunities. This review is focused on the many methods used by viruses to perturb host CRLs, focusing on substrate sequestration and viral regulation of E3 activity.",2014 Oct 13,"['Mahon, Cathal', 'Krogan, Nevan J.', 'Craik, Charles S.', 'Pick, Elah']",Biomolecules,,,True
1613fd55dff3cde4f7f32fd5b667e548f860b5d3,PMC,Multiplex PCR analysis of clusters of unexplained viral respiratory tract infection in Cambodia,http://dx.doi.org/10.1186/s12985-014-0224-x,PMC4280028,25514971,CC BY,"BACKGROUND: Fevers of unknown origin constitute a substantial disease burden in Southeast Asia. In majority of the cases, the cause of acute febrile illness is not identified. METHODS: We used MassTag PCR, a multiplex assay platform, to test for the presence of 15 viral respiratory agents from 85 patients with unexplained respiratory illness representing six disease clusters that occurred in Cambodia between 2009 and 2012. RESULTS: We detected a virus in 37 (44%) of the cases. Human rhinovirus, the virus detected most frequently, was found in both children and adults. The viruses most frequently detected in children and adults, respectively, were respiratory syncytial virus and enterovirus 68. Sequence analysis indicated that two distinct clades of enterovirus 68 were circulating during this time period. CONCLUSIONS: This is the first report of enterovirus 68 in Cambodia and contributes to the appreciation of this virus as an important respiratory pathogen.",2014 Dec 17,"['Ly, Nary', 'Tokarz, Rafal', 'Mishra, Nischay', 'Sameroff, Stephen', 'Jain, Komal', 'Rachmat, Agus', 'An, Ung Sam', 'Newell, Steven', 'Harrison, Dustin J', 'Lipkin, W Ian']",Virol J,,,True
5d7ef1b6d6d20f3a2d0c1cad4daa1496ef8a195b,PMC,Novel PDE4 Inhibitors Derived from Chinese Medicine Forsythia,http://dx.doi.org/10.1371/journal.pone.0115937,PMC4280171,25549252,CC BY,"Cyclic adenosine monophosphate (cAMP) is a crucial intracellular second messenger molecule that converts extracellular molecules to intracellular signal transduction pathways generating cell- and stimulus-specific effects. Importantly, specific phosphodiesterase (PDE) subtypes control the amplitude and duration of cAMP-induced physiological processes and are therefore a prominent pharmacological target currently used in a variety of fields. Here we tested the extracts from traditional Chinese medicine, Forsythia suspense seeds, which have been used for more than 2000 years to relieve respiratory symptoms. Using structural-functional analysis we found its major lignin, Forsynthin, acted as an immunosuppressant by inhibiting PDE4 in inflammatory and immune cell. Moreover, several novel, selective small molecule derivatives of Forsythin were tested in vitro and in murine models of viral and bacterial pneumonia, sepsis and cytokine-driven systemic inflammation. Thus, pharmacological targeting of PDE4 may be a promising strategy for immune-related disorders characterized by amplified host inflammatory response.",2014 Dec 30,"['Coon, Tiffany A.', 'McKelvey, Alison C.', 'Weathington, Nate M.', 'Birru, Rahel L.', 'Lear, Travis', 'Leikauf, George D.', 'Chen, Bill B.']",PLoS One,,,True
4cbd54dab5ad14f6d8c5ad9fb9bc223cb4431ba3,PMC,Epidemiology of Pathogen-Specific Respiratory Infections among Three US Populations,http://dx.doi.org/10.1371/journal.pone.0114871,PMC4280218,25549089,CC0,"BACKGROUND: Diagnostic tests for respiratory infections can be costly and time-consuming. Improved characterization of specific respiratory pathogens by identifying frequent signs, symptoms and demographic characteristics, along with improving our understanding of coinfection rates and seasonality, may improve treatment and prevention measures. METHODS: Febrile respiratory illness (FRI) and severe acute respiratory infection (SARI) surveillance was conducted from October 2011 through March 2013 among three US populations: civilians near the US–Mexico border, Department of Defense (DoD) beneficiaries, and military recruits. Clinical and demographic questionnaire data and respiratory swabs were collected from participants, tested by PCR for nine different respiratory pathogens and summarized. Age stratified characteristics of civilians positive for influenza and recruits positive for rhinovirus were compared to other and no/unknown pathogen. Seasonality and coinfection rates were also described. RESULTS: A total of 1444 patients met the FRI or SARI case definition and were enrolled in this study. Influenza signs and symptoms varied across age groups of civilians. Recruits with rhinovirus had higher percentages of pneumonia, cough, shortness of breath, congestion, cough, less fever and longer time to seeking care and were more likely to be male compared to those in the no/unknown pathogen group. Coinfections were found in 6% of all FRI/SARI cases tested and were most frequently seen among children and with rhinovirus infections. Clear seasonal trends were identified for influenza, rhinovirus, and respiratory syncytial virus. CONCLUSIONS: The age-stratified clinical characteristics associated with influenza suggest that age-specific case definitions may improve influenza surveillance and identification. Improving identification of rhinoviruses, the most frequent respiratory infection among recruits, may be useful for separating out contagious individuals, especially when larger outbreaks occur. Overall, describing the epidemiology of pathogen specific respiratory diseases can help improve clinical diagnoses, establish baselines of infection, identify outbreaks, and help prioritize the development of new vaccines and treatments.",2014 Dec 30,"['Radin, Jennifer M.', 'Hawksworth, Anthony W.', 'Kammerer, Peter E.', 'Balansay, Melinda', 'Raman, Rema', 'Lindsay, Suzanne P.', 'Brice, Gary T.']",PLoS One,,,True
31a8187c739fcc29ee62764d0c8da44bdc1b4d8d,PMC,Hepatitis C Virus Life Cycle and Lipid Metabolism,http://dx.doi.org/10.3390/biology3040892,PMC4280516,25517881,CC BY,"Hepatitis C Virus (HCV) infects over 150 million people worldwide. In most cases HCV infection becomes chronic, causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. HCV affects the cholesterol homeostasis and at the molecular level, every step of the virus life cycle is intimately connected to lipid metabolism. In this review, we present an update on the lipids and apolipoproteins that are involved in the HCV infectious cycle steps: entry, replication and assembly. Moreover, the result of the assembly process is a lipoviroparticle, which represents a peculiarity of hepatitis C virion. This review illustrates an example of an intricate virus-host interaction governed by lipid metabolism.",2014 Dec 15,"['Popescu, Costin-Ioan', 'Riva, Laura', 'Vlaicu, Ovidiu', 'Farhat, Rayan', 'Rouillé, Yves', 'Dubuisson, Jean']",Biology (Basel),,,True
b8915fde10e62d4b033a9141910e5639590f0bae,PMC,Plant-based solutions for veterinary immunotherapeutics and prophylactics,http://dx.doi.org/10.1186/s13567-014-0117-4,PMC4280687,25559098,CC BY,"An alarming increase in emergence of antibiotic resistance among pathogens worldwide has become a serious threat to our ability to treat infectious diseases according to the World Health Organization. Extensive use of antibiotics by livestock producers promotes the spread of new resistant strains, some of zoonotic concern, which increases food-borne illness in humans and causes significant economic burden on healthcare systems. Furthermore, consumer preferences for meat/poultry/fish produced without the use of antibiotics shape today’s market demand. So, it is viewed as inevitable by the One Health Initiative that humans need to reduce the use of antibiotics and turn to alternative, improved means to control disease: vaccination and prophylactics. Besides the intense research focused on novel therapeutic molecules, both these strategies rely heavily on the availability of cost-effective, efficient and scalable production platforms which will allow large-volume manufacturing for vaccines, antibodies and other biopharmaceuticals. Within this context, plant-based platforms for production of recombinant therapeutic proteins offer significant advantages over conventional expression systems, including lack of animal pathogens, low production costs, fast turnaround and response times and rapid, nearly-unlimited scalability. Also, because dried leaves and seeds can be stored at room temperature for lengthy periods without loss of recombinant proteins, plant expression systems have the potential to offer lucrative benefits from the development of edible vaccines and prophylactics, as these would not require “cold chain” storage and transportation, and could be administered in mass volumes with minimal processing. Several biotechnology companies currently have developed and adopted plant-based platforms for commercial production of recombinant protein therapeutics. In this manuscript, we outline the challenges in the process of livestock immunization as well as the current plant biotechnology developments aimed to address these challenges.",2014 Dec 31,"['Kolotilin, Igor', 'Topp, Ed', 'Cox, Eric', 'Devriendt, Bert', 'Conrad, Udo', 'Joensuu, Jussi', 'Stöger, Eva', 'Warzecha, Heribert', 'McAllister, Tim', 'Potter, Andrew', 'McLean, Michael D', 'Hall, J Christopher', 'Menassa, Rima']",Vet Res,,,True
f7bb1f005066cb4930f83cde4cdc1ff3fe411def,PMC,Overview of the 3rd isirv-Antiviral Group Conference – advances in clinical management,http://dx.doi.org/10.1111/irv.12293,PMC4280814,25399715,CC BY,"This review highlights the main points which emerged from the presentations and discussions at the 3rd isirv-Antiviral Group Conference - advances in clinical management. The conference covered emerging and potentially pandemic influenza viruses and discussed novel/pre-licensure therapeutics and currently approved antivirals and vaccines for the control of influenza. Current data on approved and novel treatments for non-influenza respiratory viruses such as MERS-CoV, respiratory syncytial virus (RSV) and rhinoviruses and the challenges of treating immunocompromised patients with respiratory infections was highlighted.",2015 Jan 15,"['Hurt, Aeron C', 'Hui, David S', 'Hay, Alan', 'Hayden, Frederick G']",Influenza Other Respir Viruses,,,True
4ae32ac7470a95f95ccd2309bfb62a990c1e0e16,PMC,Culturing of respiratory viruses in well-differentiated pseudostratified human airway epithelium as a tool to detect unknown viruses,http://dx.doi.org/10.1111/irv.12297,PMC4280819,25482367,CC BY,"BACKGROUND: Currently, virus discovery is mainly based on molecular techniques. Here, we propose a method that relies on virus culturing combined with state-of-the-art sequencing techniques. The most natural ex vivo culture system was used to enable replication of respiratory viruses. METHOD: Three respiratory clinical samples were tested on well-differentiated pseudostratified tracheobronchial human airway epithelial (HAE) cultures grown at an air–liquid interface, which resemble the airway epithelium. Cells were stained with convalescent serum of the patients to identify infected cells and apical washes were analyzed by VIDISCA-454, a next-generation sequencing virus discovery technique. RESULTS: Infected cells were observed for all three samples. Sequencing subsequently indicated that the cells were infected by either human coronavirus OC43, influenzavirus B, or influenzavirus A. The sequence reads covered a large part of the genome (52%, 82%, and 57%, respectively). CONCLUSION: We present here a new method for virus discovery that requires a virus culture on primary cells and an antibody detection. The virus in the harvest can be used to characterize the viral genome sequence and cell tropism, but also provides progeny virus to initiate experiments to fulfill the Koch's postulates.",2015 Jan 4,"['Jazaeri Farsani, Seyed Mohammad', 'Deijs, Martin', 'Dijkman, Ronald', 'Molenkamp, Richard', 'Jeeninga, Rienk E', 'Ieven, Margareta', 'Goossens, Herman', 'van der Hoek, Lia']",Influenza Other Respir Viruses,,,True
e0d7ff094aad4031bc73a82ae7b4dd6e5f8723c7,PMC,Identification of an Unclassified Paramyxovirus in Coleura afra: A Potential Case of Host Specificity,http://dx.doi.org/10.1371/journal.pone.0115588,PMC4281239,25551455,CC BY,"Bats are known to harbor multiple paramyxoviruses. Despite the creation of two new genera, Aquaparamyxovirus and Ferlavirus, to accommodate this increasing diversity, several recently isolated or characterized viruses remain unclassified beyond the subfamily level. In the present study, among 985 bats belonging to 6 species sampled in the Belinga caves of Gabon, RNA of an unclassified paramyxovirus (Belinga bat virus, BelPV) was discovered in 14 African sheath-tailed bats (Coleura afra), one of which exhibited several hemorrhagic lesions at necropsy, and viral sequence was obtained in two animals. Phylogenetically, BelPV is related to J virus and Beilong virus (BeiPV), two other unclassified paramyxoviruses isolated from rodents. In the diseased BelPV-infected C. afra individual, high viral load was detected in the heart, and the lesions were consistent with those reported in wild rodents and mice experimentally infected by J virus. BelPV was not detected in other tested bat species sharing the same roosting sites and living in very close proximity with C. afra in the two caves sampled, suggesting that this virus may be host-specific for C. afra. The mode of transmission of this paramyxovirus in bat populations remains to be discovered.",2014 Dec 31,"['Maganga, Gael D.', 'Bourgarel, Mathieu', 'Obame Nkoghe, Judicael', ""N'Dilimabaka, Nadine"", 'Drosten, Christian', 'Paupy, Christophe', 'Morand, Serge', 'Drexler, Jan Felix', 'Leroy, Eric M.']",PLoS One,,,True
06e2a26a1925334deaf6621d3b2763924de55b14,PMC,Epidemiologic data and pathogen genome sequences: a powerful synergy for public health,http://dx.doi.org/10.1186/s13059-014-0538-4,PMC4282151,25418119,CC BY,"Epidemiologists aim to inform the design of public health interventions with evidence on the evolution, emergence and spread of infectious diseases. Sequencing of pathogen genomes, together with date, location, clinical manifestation and other relevant data about sample origins, can contribute to describing nearly every aspect of transmission dynamics, including local transmission and global spread. The analyses of these data have implications for all levels of clinical and public health practice, from institutional infection control to policies for surveillance, prevention and treatment. This review highlights the range of epidemiological questions that can be addressed from the combination of genome sequence and traditional ‘line lists’ (tables of epidemiological data where each line includes demographic and clinical features of infected individuals). We identify opportunities for these data to inform interventions that reduce disease incidence and prevalence. By considering current limitations of, and challenges to, interpreting these data, we aim to outline a research agenda to accelerate the genomics-driven transformation in public health microbiology.",2014 Nov 18,"['Grad, Yonatan H', 'Lipsitch, Marc']",Genome Biol,,,True
1f23a8772f471052f70a35fe6921865c014cad71,PMC,"Middle East Respiratory Syndrome Coronavirus Antibody Reactors Among Camels in Dubai, United Arab Emirates, in 2005",http://dx.doi.org/10.1111/tbed.12212,PMC4282458,24456414,CC BY,"We tested, using a low starting dilution, sequential serum samples from dromedary camels, sheep and horses collected in Dubai from February/April to October of 2005 and from dromedary camels for export/import testing between Canada and USA in 2000–2001. Using a standard Middle East respiratory syndrome coronavirus (MERS-CoV) neutralization test, serial sera from three sheep and three horses were all negative while sera from 9 of 11 dromedary camels from Dubai were positive for antibodies supported by similar results in a MERS-CoV recombinant partial spike protein antibody ELISA. The two negative Dubai camels were both dromedary calves and remained negative over the 5 months studied. The six dromedary samples from USA and Canada were negative in both tests. These results support the recent findings that infection with MERS-CoV or a closely related virus is not a new occurrence in camels in the Middle East. Therefore, interactions of MERS-CoV at the human–animal interface may have been ongoing for several, perhaps many, years and by inference, a widespread pandemic may be less likely unless significant evolution of the virus allow accelerated infection and spread potential in the human population.",2014 Apr 24,"['Alexandersen, S', 'Kobinger, G P', 'Soule, G', 'Wernery, U']",Transbound Emerg Dis,,,True
77c758dbd0cc50cb84be51107f421313cba47320,PMC,A Computational Approach for Predicting Role of Human MicroRNAs in MERS-CoV Genome,http://dx.doi.org/10.1155/2014/967946,PMC4283225,25610462,CC BY,"The new epidemic Middle East Respiratory Syndrome (MERS) is caused by a type of human coronavirus called MERS-CoV which has global fatality rate of about 30%. We are investigating potential antiviral therapeutics against MERS-CoV by using host microRNAs (miRNAs) which may downregulate viral gene expression to quell viral replication. We computationally predicted potential 13 cellular miRNAs from 11 potential hairpin sequences of MERS-CoV genome. Our study provided an interesting hypothesis that those miRNAs, that is, hsa-miR-628-5p, hsa-miR-6804-3p, hsa-miR-4289, hsa-miR-208a-3p, hsa-miR-510-3p, hsa-miR-18a-3p, hsa-miR-329-3p, hsa-miR-548ax, hsa-miR-3934-5p, hsa-miR-4474-5p, hsa-miR-7974, hsa-miR-6865-5p, and hsa-miR-342-3p, would be antiviral therapeutics against MERS-CoV infection.",2014 Dec 23,"['Hasan, Md Mahmudul', 'Akter, Rozina', 'Ullah, Md. Shahin', 'Abedin, Md. Jaynul', 'Ullah, G. M. Ahsan', 'Hossain, Md. Zakir']",Adv Bioinformatics,,,True
815b5e537a3e7bdb7d5c7c7cd51181b9b2e245c5,PMC,The Importance of Mouse Models to Define Immunovirologic Determinants of Progressive Multifocal Leukoencephalopathy,http://dx.doi.org/10.3389/fimmu.2014.00646,PMC4283601,25601860,CC BY,"Progressive multifocal leukoencephalopathy (PML) is a severely debilitating and often fatal demyelinating disease of the central nervous system (CNS) in immunosuppressed individuals caused by JC polyomavirus (JCV), a ubiquitous human pathogen. Demyelination results from lytically infected oligodendrocytes, whose clearance is impaired in the setting of depressed JCV-specific T cell-mediated CNS surveillance. Although mutations in the viral capsid and genomic rearrangements in the viral non-coding region appear to set the stage for PML in the immunosuppressed population, mechanisms of demyelination and CNS antiviral immunity are poorly understood in large part due to absence of a tractable animal model that mimics PML neuropathology in humans. Early studies using mouse polyomavirus (MPyV) in T cell-deficient mice demonstrated productive viral replication in the CNS and demyelination; however, these findings were confounded by spinal cord compression by virus-induced vertebral bone tumors. Here, we review current literature regarding animal models of PML, focusing on current trends in antiviral T cell immunity in non-lymphoid organs, including the CNS. Advances in our understanding of polyomavirus lifecycles, viral and host determinants of persistent infection, and T cell-mediated immunity to viral infections in the CNS warrant revisiting polyomavirus CNS infection in the mouse as a bona fide animal model for JCV-PML.",2015 Jan 5,"['Frost, Elizabeth L.', 'Lukacher, Aron E.']",Front Immunol,,,True
45bb84571df3f2e42173366750302b2315783842,PMC,"Genomic analysis of emerging pathogens: methods, application and future trends",http://dx.doi.org/10.1186/s13059-014-0541-9,PMC4283782,25418281,CC BY,"The number of emerging infectious diseases is increasing. Characterizing novel or re-emerging infections is aided by the availability of pathogen genomes. In this review, we evaluate methods that exploit pathogen sequences and the contribution of genomic analysis to understand the epidemiology of recently emerged infectious diseases.",2014 Nov 22,"['Li, Lucy M', 'Grassly, Nicholas C', 'Fraser, Christophe']",Genome Biol,,,True
119585987862e9f02ef0a1748462fb38ecb95b53,PMC,Human infectious diseases in the genomics era: where do we go from here?,http://dx.doi.org/10.1186/s13059-014-0529-5,PMC4283784,25418021,CC BY,"Ripudaman K Bains is the editor of the Genome Biology special issue content on the ‘genomics of infectious diseases’, and introduces the collection in this editorial.",2014 Nov 22,"Bains, Ripudaman K",Genome Biol,,,True
bf0d0a5f74db0e532f85d90285a96f7e70670c55,PMC,Identification of Sumoylated Proteins in the Silkworm Bombyx mori,http://dx.doi.org/10.3390/ijms151222011,PMC4284691,25470021,CC BY,"Small ubiquitin-like modifier (SUMO) modification (SUMOylation) is an important and widely used reversible modification system in eukaryotic cells. It regulates various cell processes, including protein targeting, transcriptional regulation, signal transduction, and cell division. To understand its role in the model lepidoptera insect Bombyx mori, a recombinant baculovirus was constructed to express an enhanced green fluorescent protein (eGFP)-SUMO fusion protein along with ubiquitin carrier protein 9 of Bombyx mori (BmUBC9). SUMOylation substrates from Bombyx mori cells infected with this baculovirus were isolated by immunoprecipitation and identified by LC–ESI-MS/MS. A total of 68 candidate SUMOylated proteins were identified, of which 59 proteins were functionally categorized to gene ontology (GO) terms. Analysis of kyoto encyclopedia of genes and genomes (KEGG) pathways showed that 46 of the identified proteins were involved in 76 pathways that mainly play a role in metabolism, spliceosome and ribosome functions, and in RNA transport. Furthermore, SUMOylation of four candidates (polyubiquitin-C-like isoform X1, 3-hydroxyacyl-CoA dehydrogenase, cyclin-related protein FAM58A-like and GTP-binding nuclear protein Ran) were verified by co-immunoprecipitation in Drosophila schneide 2 cells. In addition, 74% of the identified proteins were predicted to have at least one SUMOylation site. The data presented here shed light on the crucial process of protein sumoylation in Bombyx mori.",2014 Dec 1,"['Tang, Xudong', 'Fu, Xuliang', 'Hao, Bifang', 'Zhu, Feng', 'Xiao, Shengyan', 'Xu, Li', 'Shen, Zhongyuan']",Int J Mol Sci,,,True
b87ddf92d90fd58bbdf08981116cd7841d75d483,PMC,What Macromolecular Crowding Can Do to a Protein,http://dx.doi.org/10.3390/ijms151223090,PMC4284756,25514413,CC BY,"The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the “real life” situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model “crowding agents”. Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of macromolecular crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area.",2014 Dec 12,"['Kuznetsova, Irina M.', 'Turoverov, Konstantin K.', 'Uversky, Vladimir N.']",Int J Mol Sci,,,True
883cb0158d0026f5e0b986a72e80266b60dfe98f,PMC,Pathogen Security-Help or Hindrance?,http://dx.doi.org/10.3389/fbioe.2014.00083,PMC4285169,25610829,CC BY,"Events over the past 15 years have resulted in the promulgation of regulations in the United States to enhance biosecurity by restricting the access to pathogens and toxins (i.e., biological select agents and toxins [BSATs]), which pose a severe threat to human being, animal, or plant health or to animal or plant products, to qualified institutions, laboratories, and scientists. These regulations also reduce biosafety concerns by imposing specific requirements on laboratories working with BSATs. Furthermore, they provide a legal framework for prosecuting someone who possesses a BSAT illegally. With the implementation of these regulations has come discussion in the scientific community about the potential of these regulations to affect the cost of doing BSAT research, hamper research and international collaborations, or whether it would stop someone with a microbiological background from isolating many of the select agents from nature.",2015 Jan 6,"Morse, Stephen A.",Front Bioeng Biotechnol,,,True
9b26e1267786a1ec02d8ede9599ec416b7e9f3cf,PMC,Finding and identifying the viral needle in the metagenomic haystack: trends and challenges,http://dx.doi.org/10.3389/fmicb.2014.00739,PMC4285800,25610431,CC BY,"Collectively, viruses have the greatest genetic diversity on Earth, occupy extremely varied niches and are likely able to infect all living organisms. Viral infections are an important issue for human health and cause considerable economic losses when agriculturally important crops or husbandry animals are infected. The advent of metagenomics has provided a precious tool to study viruses by sampling them in natural environments and identifying the genomic composition of a sample. However, reaching a clear recognition and taxonomic assignment of the identified viruses has been hampered by the computational difficulty of these problems. In this perspective paper we examine the trends in current research for the identification of viral sequences in a metagenomic sample, pinpoint the intrinsic computational difficulties for the identification of novel viral sequences within metagenomic samples, and suggest possible avenues to overcome them.",2015 Jan 7,"['Soueidan, Hayssam', 'Schmitt, Louise-Amélie', 'Candresse, Thierry', 'Nikolski, Macha']",Front Microbiol,,,True
9fe4bb195ffbcf6f450478fa94e72e099fb7d335,PMC,Detection of a novel avian influenza A (H7N9) virus in humans by multiplex one-step real-time RT-PCR assay,http://dx.doi.org/10.1186/1471-2334-14-541,PMC4286936,25298249,CC BY,"BACKGROUND: A novel avian influenza A (H7N9) virus emerged in eastern China in February 2013. 413 confirmed human cases, including 157 deaths, have been recorded as of July 31, 2014. METHODS: Clinical specimens, including throat swabs, sputum or tracheal aspirates, etc., were obtained from patients exhibiting influenza-like illness (ILIs), especially from those having pneumonia and a history of occupational exposure to poultry and wild birds. RNA was extracted from these samples and a multiplex one-step real-time RT-PCR assay was developed to specifically detect the influenza A virus (FluA). PCR primers targeted the conserved M and Rnase P (RP) genes, as well as the hemagglutinin and neuraminidase genes of the H7N9 virus. RESULTS: The multiplex assay specifically detected the avian H7N9 virus, and no cross-reaction with other common respiratory pathogens was observed. The detection limit of the assay was approximately 0.05 50% tissue culture infective doses (TCID(50)), or 100 copies per reaction. Positive detection of the H7N9 virus in sputum/tracheal aspirates was higher than in throat swabs during the surveillance of patients with ILIs. Additionally, detection of the matrix (M) and Rnase P genes aided in the determination of the novel avian H7N9 virus and ensured the quality of the clinical samples. CONCLUSIONS: These results demonstrate that the multiplex assay detected the novel avian H7N9 virus with high specificity and sensitivity, which is essential for the early diagnosis and treatment of infected patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-541) contains supplementary material, which is available to authorized users.",2014 Oct 8,"['Fan, Jian', 'Cui, David', 'Lau, Siuying', 'Xie, Guoliang', 'Guo, Xichao', 'Zheng, Shufa', 'Huang, Xiaofeng', 'Yang, Shigui', 'Yang, Xianzhi', 'Huo, Zhaoxia', 'Yu, Fei', 'Lou, Jianzhou', 'Tian, Li', 'Li, Xuefen', 'Dong, Yuejiao', 'Zhu, Qiaoyun', 'Chen, Yu']",BMC Infect Dis,,,True
bc489624c814eedf1d191c84f7ca9efce0c98e1b,PMC,Bi-specific splice-switching PMO oligonucleotides conjugated via a single peptide active in a mouse model of Duchenne muscular dystrophy,http://dx.doi.org/10.1093/nar/gku1256,PMC4288157,25468897,CC BY,"The potential for therapeutic application of splice-switching oligonucleotides (SSOs) to modulate pre-mRNA splicing is increasingly evident in a number of diseases. However, the primary drawback of this approach is poor cell and in vivo oligonucleotide uptake efficacy. Biological activities can be significantly enhanced through the use of synthetically conjugated cationic cell penetrating peptides (CPPs). Studies to date have focused on the delivery of a single SSO conjugated to a CPP, but here we describe the conjugation of two phosphorodiamidate morpholino oligonucleotide (PMO) SSOs to a single CPP for simultaneous delivery and pre-mRNA targeting of two separate genes, exon 23 of the Dmd gene and exon 5 of the Acvr2b gene, in a mouse model of Duchenne muscular dystrophy. Conjugations of PMOs to a single CPP were carried out through an amide bond in one case and through a triazole linkage (‘click chemistry’) in the other. The most active bi-specific CPP–PMOs demonstrated comparable exon skipping levels for both pre-mRNA targets when compared to individual CPP–PMO conjugates both in cell culture and in vivo in the mdx mouse model. Thus, two SSOs with different target sequences conjugated to a single CPP are biologically effective and potentially suitable for future therapeutic exploitation.",2015 Jan 9,"['Shabanpoor, Fazel', 'McClorey, Graham', 'Saleh, Amer F.', 'Järver, Peter', 'Wood, Matthew J.A.', 'Gait, Michael J.']",Nucleic Acids Res,,,True
acadcb58dfdef9e3e9981dde06e2a825c005c9c4,PMC,Subgenomic promoter recognition by the norovirus RNA-dependent RNA polymerases,http://dx.doi.org/10.1093/nar/gku1292,PMC4288183,25520198,CC BY,"The replication enzyme of RNA viruses must preferentially recognize their RNAs in an environment that contains an abundance of cellular RNAs. The factors responsible for specific RNA recognition are not well understood, in part because viral RNA synthesis takes place within enzyme complexes associated with modified cellular membrane compartments. Recombinant RNA-dependent RNA polymerases (RdRps) from the human norovirus and the murine norovirus (MNV) were found to preferentially recognize RNA segments that contain the promoter and a short template sequence for subgenomic RNA synthesis. Both the promoter and template sequence contribute to stable RdRp binding, accurate initiation of the subgenomic RNAs and efficient RNA synthesis. Using a method that combines RNA crosslinking and mass spectrometry, residues near the template channel of the MNV RdRp were found to contact the hairpin RNA motif. Mutations in the hairpin contact site in the MNV RdRp reduced MNV replication and virus production in cells. This work demonstrates that the specific recognition of the norovirus subgenomic promoter is through binding by the viral RdRp.",2015 Jan 9,"['Lin, Xiaoyan', 'Thorne, Lucy', 'Jin, Zhinan', 'Hammad, Loubna A.', 'Li, Serena', 'Deval, Jerome', 'Goodfellow, Ian G.', 'Kao, C. Cheng']",Nucleic Acids Res,,,True
4a698e56af8042a4c35a26127c4da5fc5ff7fa95,PMC,Long Non-Coding RNA BST2/BISPR is Induced by IFN and Regulates the Expression of the Antiviral Factor Tetherin,http://dx.doi.org/10.3389/fimmu.2014.00655,PMC4288319,25620967,CC BY,"Many long non-coding RNAs (lncRNAs) are expressed in cells but only a few have been well characterized. In these cases, lncRNAs have been shown to be key regulators of several cellular processes. Therefore, there is a great need to understand the function of more lncRNAs and their regulation in response to stimuli. Interferon (IFN) is a key molecule in the cellular antiviral response. IFN binding to its receptor activates transcription of several IFN-stimulated genes (ISGs) that function as potent antivirals. In addition, several ISGs are positive or negative regulators of the IFN pathway. This is essential to ensure a strong antiviral response and a later return of the cell to homeostasis. As the ISGs described to date are coding genes, we sought to determine whether IFN also regulates the expression of long non-coding ISGs. To this aim, we used RNA sequencing to analyze the transcriptome of control and HuH7 cells treated with IFNα2. The results show that IFN-treatment regulates the expression of several unknown non-coding transcripts. We have validated two lncRNAs upregulated after treatment with different doses of type I IFNα2 in different cells or with type III IFNλ. These lncRNAs were also induced by influenza and vesicular stomatitis virus mutants unable to block the IFN response, but not by several wild-type lytic viruses tested. These lncRNA genes were named lncISG15 and lncBST2 as they are located close to ISGs ISG15 and BST2, respectively. Interestingly, inhibition experiments showed that lncBST2 is a positive regulator of BST2. Therefore lncBST2 has been renamed BISPR, from BST2 IFN-stimulated positive regulator. Our results may have therapeutic implications as lncBST2/BISPR, but also lncISG15 and their coding neighbors, are increased in cells infected with hepatitis C virus and in the liver of infected patients. These results allow us to hypothesize that several lncRNAs could be activated by IFN to control the potency of the antiviral IFN response.",2015 Jan 9,"['Barriocanal, Marina', 'Carnero, Elena', 'Segura, Victor', 'Fortes, Puri']",Front Immunol,,,True
642113801b5c8906fb7eb9bf989d0c4fabd712e1,PMC,Using Modelling to Disentangle the Relative Contributions of Zoonotic and Anthroponotic Transmission: The Case of Lassa Fever,http://dx.doi.org/10.1371/journal.pntd.0003398,PMC4288732,25569707,CC BY,"BACKGROUND: Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. METHODOLOGY/PRINCIPAL FINDINGS: Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost [Image: see text] of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals (‘super-spreaders’), as we found only [Image: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Image: see text], with a maximum value up to [Image: see text]. CONCLUSIONS/SIGNIFICANCE: This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.",2015 Jan 8,"['Lo Iacono, Giovanni', 'Cunningham, Andrew A.', 'Fichet-Calvet, Elisabeth', 'Garry, Robert F.', 'Grant, Donald S.', 'Khan, Sheik Humarr', 'Leach, Melissa', 'Moses, Lina M.', 'Schieffelin, John S.', 'Shaffer, Jeffrey G.', 'Webb, Colleen T.', 'Wood, James L. N.']",PLoS Negl Trop Dis,,,True
6c87c1b2b6d84e2e3fbd504840d8434adc045833,PMC,Using Modelling to Disentangle the Relative Contributions of Zoonotic and Anthroponotic Transmission: The Case of Lassa Fever,http://dx.doi.org/10.1371/journal.pntd.0003398,PMC4288732,25569707,CC BY,"BACKGROUND: Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. METHODOLOGY/PRINCIPAL FINDINGS: Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost [Image: see text] of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals (‘super-spreaders’), as we found only [Image: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Image: see text], with a maximum value up to [Image: see text]. CONCLUSIONS/SIGNIFICANCE: This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.",2015 Jan 8,"['Lo Iacono, Giovanni', 'Cunningham, Andrew A.', 'Fichet-Calvet, Elisabeth', 'Garry, Robert F.', 'Grant, Donald S.', 'Khan, Sheik Humarr', 'Leach, Melissa', 'Moses, Lina M.', 'Schieffelin, John S.', 'Shaffer, Jeffrey G.', 'Webb, Colleen T.', 'Wood, James L. N.']",PLoS Negl Trop Dis,,,False
d8196519b0be213e70c77973a63cd4a13f5532c3,PMC,Using Modelling to Disentangle the Relative Contributions of Zoonotic and Anthroponotic Transmission: The Case of Lassa Fever,http://dx.doi.org/10.1371/journal.pntd.0003398,PMC4288732,25569707,CC BY,"BACKGROUND: Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. METHODOLOGY/PRINCIPAL FINDINGS: Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost [Image: see text] of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals (‘super-spreaders’), as we found only [Image: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Image: see text], with a maximum value up to [Image: see text]. CONCLUSIONS/SIGNIFICANCE: This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.",2015 Jan 8,"['Lo Iacono, Giovanni', 'Cunningham, Andrew A.', 'Fichet-Calvet, Elisabeth', 'Garry, Robert F.', 'Grant, Donald S.', 'Khan, Sheik Humarr', 'Leach, Melissa', 'Moses, Lina M.', 'Schieffelin, John S.', 'Shaffer, Jeffrey G.', 'Webb, Colleen T.', 'Wood, James L. N.']",PLoS Negl Trop Dis,,,True
3b4888c664b3d2fa758325160b185a453b6f8bb4,PMC,How to approach and treat viral infections in ICU patients,http://dx.doi.org/10.1186/1471-2334-14-321,PMC4289200,25431007,CC BY,Patients with severe viral infections are often hospitalized in intensive care units (ICUs) and recent studies underline the frequency of viral detection in ICU patients. Viral infections in the ICU often involve the respiratory or the central nervous system and can cause significant morbidity and mortality especially in immunocompromised patients. The mainstay of therapy of viral infections is supportive care and antiviral therapy when available. Increased understanding of the molecular mechanisms of viral infection has provided great potential for the discovery of new antiviral agents that target viral proteins or host proteins that regulate immunity and are involved in the viral life cycle. These novel treatments need to be further validated in animal and human randomized controlled studies.,2014 Nov 28,"['Kelesidis, Theodoros', 'Mastoris, Ioannis', 'Metsini, Aliki', 'Tsiodras, Sotirios']",BMC Infect Dis,,,True
027f86c44365e0ba6a6c26e24134c4c3e98a72ef,PMC,Virus-host interactomics: new insights and opportunities for antiviral drug discovery,http://dx.doi.org/10.1186/s13073-014-0115-1,PMC4295275,25593595,CC BY,"The current therapeutic arsenal against viral infections remains limited, with often poor efficacy and incomplete coverage, and appears inadequate to face the emergence of drug resistance. Our understanding of viral biology and pathophysiology and our ability to develop a more effective antiviral arsenal would greatly benefit from a more comprehensive picture of the events that lead to viral replication and associated symptoms. Towards this goal, the construction of virus-host interactomes is instrumental, mainly relying on the assumption that a viral infection at the cellular level can be viewed as a number of perturbations introduced into the host protein network when viral proteins make new connections and disrupt existing ones. Here, we review advances in interactomic approaches for viral infections, focusing on high-throughput screening (HTS) technologies and on the generation of high-quality datasets. We show how these are already beginning to offer intriguing perspectives in terms of virus-host cell biology and the control of cellular functions, and we conclude by offering a summary of the current situation regarding the potential development of host-oriented antiviral therapeutics.",2014 Nov 29,"['de Chassey, Benoît', 'Meyniel-Schicklin, Laurène', 'Vonderscher, Jacky', 'André, Patrice', 'Lotteau, Vincent']",Genome Med,,,True
5999e5bdbde2e8bfb3389bfe0ea96e229245cf67,PMC,"Genomics and infectious disease: a call to identify the ethical, legal and social implications for public health and clinical practice",http://dx.doi.org/10.1186/s13073-014-0106-2,PMC4295297,25593592,CC BY,"Advances in genomics are contributing to the development of more effective, personalized approaches to the prevention and treatment of infectious diseases. Genetic sequencing technologies are furthering our understanding of how human and pathogen genomic factors - and their interactions - contribute to individual differences in immunologic responses to vaccines, infections and drug therapies. Such understanding will influence future policies and procedures for infectious disease management. With the potential for tailored interventions for particular individuals, populations or subpopulations, ethical, legal and social implications (ELSIs) may arise for public health and clinical practice. Potential considerations include balancing health-related benefits and harms between individuals and the larger community, minimizing threats to individual privacy and autonomy, and ensuring just distribution of scarce resources. In this Opinion, we consider the potential application of pathogen and host genomic information to particular viral infections that have large-scale public health consequences but differ in ELSI-relevant characteristics such as ease of transmission, chronicity, severity, preventability and treatability. We argue for the importance of anticipating these ELSI issues in advance of new scientific discoveries, and call for the development of strategies for identifying and exploring ethical questions that should be considered as clinical, public health and policy decisions are made.",2014 Nov 18,"['Geller, Gail', 'Dvoskin, Rachel', 'Thio, Chloe L', 'Duggal, Priya', 'Lewis, Michelle H', 'Bailey, Theodore C', 'Sutherland, Andrea', 'Salmon, Daniel A', 'Kahn, Jeffrey P']",Genome Med,,,True
ab52aa56838160b5ec7a015a05ef76fc06129b5e,PMC,"MALDI-TOF mass spectrometry and identification of new bacteria species in air samples from Makkah, Saudi Arabia",http://dx.doi.org/10.1186/1756-0500-7-892,PMC4295573,25491533,CC BY,"BACKGROUND: During the Hajj season, respiratory symptoms are very common among pilgrims. Here, we investigated the viable bacterial population in air samples collected around the slaughterhouses used during the Hajj. METHODS AND RESULTS: We collected air samples on three days from four different sites: slaughterhouses at Al-Kakia, Al-Meaisim and Al-Sharaia, and from a waste disposal area designated for the remnants of slaughter. Samples were cultured on blood agar plates for 48 h, and bacterial isolates were identified using MALDI-TOF MS. A dendrogram using the spectra of the unidentified bacterial species was constructed, and PCR amplification and sequencing of the 16S rRNA gene was performed for one isolate per cluster. In total, 2500 colonies appeared on the nutrient agar plates, and 244 were purified for further analysis. Good identification was obtained for 202 (83%) isolates by MALDI-TOF MS. The most common genera were Bacillus (n = 94, 45%) and Staphyloccocus (n = 55, 26%). Poor identification was obtained for 42 (17%) isolates, and their spectra clustering revealed that these isolates belonged to 10 species. Four of these were considered to be new species. CONCLUSIONS: During the Hajj, the air was contaminated by many environmental bacterial agents, and MALDI-TOF MS was successfully adapted for their rapid identification.",2014 Dec 9,"['Angelakis, Emmanouil', 'Yasir, Muhammad', 'Azhar, Esam I', 'Papadioti, Anastasia', 'Bibi, Fehmida', 'Aburizaiza, Asad S', 'Metidji, Sarah', 'Memish, Ziad A', 'Ashshi, Ahmad M', 'Hassan, Ahmed M', 'Harakeh, Steve', 'Gautret, Philippe', 'Raoult, Didier']",BMC Res Notes,,,True
bc589336315df8e93a0fcd4fda5442bf982e9b6d,PMC,Accuracy of using automated methods for detecting adverse events from electronic health record data: a research protocol,http://dx.doi.org/10.1186/s13012-014-0197-6,PMC4296680,25567422,CC BY,"BACKGROUND: Adverse events are associated with significant morbidity, mortality and cost in hospitalized patients. Measuring adverse events is necessary for quality improvement, but current detection methods are inaccurate, untimely and expensive. The advent of electronic health records and the development of automated methods for encoding and classifying electronic narrative data, such as natural language processing, offer an opportunity to identify potentially better methods. The objective of this study is to determine the accuracy of using automated methods for detecting three highly prevalent adverse events: a) hospital-acquired pneumonia, b) catheter-associated bloodstream infections, and c) in-hospital falls. METHODS/DESIGN: This validation study will be conducted at two large Canadian academic health centres: the McGill University Health Centre (MUHC) and The Ottawa Hospital (TOH). The study population consists of all medical, surgical and intensive care unit patients admitted to these centres between 2008 and 2014. An automated detection algorithm will be developed and validated for each of the three adverse events using electronic data extracted from multiple clinical databases. A random sample of MUHC patients will be used to develop the automated detection algorithms (cohort 1, development set). The accuracy of these algorithms will be assessed using chart review as the reference standard. Then, receiver operating characteristic curves will be used to identify optimal cut points for each of the data sources. Multivariate logistic regression and the areas under curve (AUC) will be used to identify the optimal combination of data sources that maximize the accuracy of adverse event detection. The most accurate algorithms will then be validated on a second random sample of MUHC patients (cohort 1, validation set), and accuracy will be measured using chart review as the reference standard. The most accurate algorithms validated at the MUHC will then be applied to TOH data (cohort 2), and their accuracy will be assessed using a reference standard assessment of the medical chart. DISCUSSION: There is a need for more accurate, timely and efficient measures of adverse events in acute care hospitals. This is a critical requirement for evaluating the effectiveness of preventive interventions and for tracking progress in patient safety through time.",2015 Jan 8,"['Rochefort, Christian M', 'Buckeridge, David L', 'Forster, Alan J']",Implement Sci,,,True
44f34175ad29353c40276c6d19ee257e7511c8ef,PMC,Identification of VP1 peptides diagnostic of encephalomyocarditis virus from swine,http://dx.doi.org/10.1186/s12985-014-0226-8,PMC4297377,25547933,CC BY,"BACKGROUND: Encephalomyocarditis virus (EMCV) can cause myocarditis, respiratory failure, reproductive failure, and sudden death in pre-weaned piglets, which has been isolated in China. EMCV VP1 protein was one of the most important structural proteins and played an important role in the protective immunity. In this study, 10 monoclonal antibodies (McAbs) against EMCV VP1 were screened and identified. RESULTS: Epitope mapping results indicated that McAbs (6E11, 7A7, 7C9) specifically recognized the linear epitopes V(2)ENAEK(7), McAbs (1D1, 2A2, 5A1, 5A11, 5G1) recognized the epitope F(19)VAQPVY(25), and McAbs 1G8 and 3A9 recognized P(42)IGAFTVK(49). Protein sequence alignment of VP1 with 16 EMCV isolates indicated that the epitope F(19)VAQPVY(25) was conserved in all the reference strains. The epitopes P(42)IGAFTVK(49) and V(2)ENAEK(7) only had 1 or 2 variable amino acid among the reference strains. The 3D model analysis results showed that these epitopes presented as spheres were shown within the context of the complete particle. CONCLUSIONS: In this study, ten McAbs against EMCV VP1 were developed and three B-cells epitopes (2-7aa, 19-25aa and 42-49aa) were defined in VP1. All the results herein will promote the future investigations into the function of VP1 of EMCV and development of diagnostic methods of EMCV.",2014 Dec 30,"['Bai, Juan', 'Chen, Xinhui', 'Jiang, Kangfu', 'Zeshan, Basit', 'Jiang, Ping']",Virol J,,,True
574285d317ef91b77f2dc770a3dbf2a9b514de21,PMC,Molecular and clinical study on prevalence of feline herpesvirus type 1 and calicivirus in correlation with feline leukemia and immunodeficiency viruses,,PMC4299990,25610576,CC BY,"Upper respiratory tract diseases (URTD) are common clinical problem in cats worldwide. Feline calicivirus (FCV) and feline herpesvirus type 1 (FHV-1) are the main primary pathogens. Feline immunodeficiency virus (FIV) and Feline leukemia virus (FeLV) are also among the most common infectious diseases of cats which suppress the immunity. Oropharyngeal and conjunctival swabs and blood samples were taken from 16 cats with clinical signs of URTD and 26 clinically healthy cats. PCR and RT-PCR were used to detect FHV/FIV or FCV/FeLV infections, respectively. Feline calicivirus was detected in all cats with URTD and 87.00% and 93.00% of them were positive for FIV and FeLV, respectively. Feline herpesvirus rate of infection was 43.00% in sick cats. In clinically normal cats, prevalence rates of FCV and FHV were about 50.00%, but FIV and FeLV rates (42.00% and 65.00% respectively) were higher compared to other studies. Stomatitis was observed in 50.00% of cats with URTD. The main causative agent of corneal ulcers is FHV-1, but in 50.00% of cats with corneal ulcers, FCV was detected alone. It seems new variants of Caliciviruses are the main causative agents to attack uncommon tissues like cornea, although retroviral infections may be in the background of these various signs. The high retroviral prevalence may be due to existence of large population of stray cats. This is the first molecular study of FeLV and FCV in Iran and seems that FCV and FHV prevalence rates in FIV or FeLV infected cats is more than other non-infected ones.",2014 Autumn,"['Najafi, Hamideh', 'Madadgar, Omid', 'Jamshidi, Shahram', 'Ghalyanchi Langeroudi, Arash', 'Darzi Lemraski, Mahdieh']",Vet Res Forum,,,True
215d86822474f970baa8ed894e23940bc4a85c79,PMC,Molecular detection of infectious bronchitis and Newcastle disease viruses in broiler chickens with respiratory signs using Duplex RT-PCR,,PMC4299999,25610585,CC BY,"Infectious bronchitis (IB) and Newcastle disease (ND) are highly contagious and the most economically important diseases of the poultry affecting respiratory tract and causing economic losses in poultry industry throughout the world. In the present study, the simultaneous detection and differentiation of causative agents of these diseases were investigated using duplex-RT-PCR. RNA was extracted from vaccinal and reference strains of infectious bronchitis virus (IBV) and Newcastle disease virus (NDV) and then cDNA was synthesized. Using two universal primer sets for detection of IBV and NDV, the duplex-RT-PCR was developed. In order to assess the efficiency of the developed duplex RT-PCR, a number of 12 broiler farms with the symptoms of respiratory tract infection was sampled (trachea, lung and kidney were sampled from affected birds suspicious for IBV and NDV infections). After RNA extraction from tissues and cDNA synthesis, the presence of IBV and NDV genome were investigated using duplex-PCR. The results showed that three of twelve examined broiler farms were positive for IBV and two farms were positive for NDV and IBV. The results revealed that the duplex-RT-PCR is a quick and sensitive procedure for simultaneously detecting IBV and NDV in birds with respiratory infections.",2014 Autumn,"['Saba Shirvan, Aylar', 'Mardani, Karim']",Vet Res Forum,,,True
368cbceb0d0e8ad64b484f330c03d950394bf397,PMC,Using internet search queries for infectious disease surveillance: screening diseases for suitability,http://dx.doi.org/10.1186/s12879-014-0690-1,PMC4300155,25551277,CC BY,"BACKGROUND: Internet-based surveillance systems provide a novel approach to monitoring infectious diseases. Surveillance systems built on internet data are economically, logistically and epidemiologically appealing and have shown significant promise. The potential for these systems has increased with increased internet availability and shifts in health-related information seeking behaviour. This approach to monitoring infectious diseases has, however, only been applied to single or small groups of select diseases. This study aims to systematically investigate the potential for developing surveillance and early warning systems using internet search data, for a wide range of infectious diseases. METHODS: Official notifications for 64 infectious diseases in Australia were downloaded and correlated with frequencies for 164 internet search terms for the period 2009–13 using Spearman’s rank correlations. Time series cross correlations were performed to assess the potential for search terms to be used in construction of early warning systems. RESULTS: Notifications for 17 infectious diseases (26.6%) were found to be significantly correlated with a selected search term. The use of internet metrics as a means of surveillance has not previously been described for 12 (70.6%) of these diseases. The majority of diseases identified were vaccine-preventable, vector-borne or sexually transmissible; cross correlations, however, indicated that vector-borne and vaccine preventable diseases are best suited for development of early warning systems. CONCLUSIONS: The findings of this study suggest that internet-based surveillance systems have broader applicability to monitoring infectious diseases than has previously been recognised. Furthermore, internet-based surveillance systems have a potential role in forecasting emerging infectious disease events, especially for vaccine-preventable and vector-borne diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0690-1) contains supplementary material, which is available to authorized users.",2014 Dec 31,"['Milinovich, Gabriel J', 'Avril, Simon M R', 'Clements, Archie C A', 'Brownstein, John S', 'Tong, Shilu', 'Hu, Wenbiao']",BMC Infect Dis,,,True
cec21bb25c57f0e17f672a7ed7b91a01bd371ee7,PMC,Bovine respiratory syncytial virus and bovine coronavirus in Swedish organic and conventional dairy herds,http://dx.doi.org/10.1186/s13028-014-0091-x,PMC4300160,25582919,CC BY,"BACKGROUND: Infections with bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BoCV) are endemic to the cattle populations in most countries, causing respiratory and/or enteric disease. It has been demonstrated that herds can remain free from these infections for several years also in high prevalence areas. Organically managed (OM) dairy herds have been shown to have lower seroprevalence of both viruses compared to conventionally managed (CM) herds. The objective of this study was to challenge the hypothesis of a lower occurrence of BRSV and BoCV in OM compared to CM dairy herds. In November 2011, May 2012 and May 2013 milk samples from four homebred primiparous cows were collected in 75 to 65 OM and 69 to 62 CM herds. The antibody status regarding BRSV and BoCV was analysed with commercial indirect ELISAs. Herds were classified as positive if at least one individual sample was positive. RESULTS: The prevalence of positive herds ranged from 73.4% to 82.3% for BRSV and from 76.8% to 85.3% for BoCV among OM and CM herds, over the three sampling occasions. There was no statistically significant difference between OM and CM herds at any sampling occasion. The incidence risk of newly infected herds did not differ statistically between OM and CM herds at any sampling occasion, neither for BRSV nor for BoCV. The incidence of herds turning sero-negative between samplings corresponded to the incidence of newly infected. Bulk tank milk (BTM) samples were also sampled in the herds and analysed. Several herds were negative on individual samples but positive in BTM. Herd-level data on production, health and reproduction were retrieved from VÄXA Sweden and the study herds were representative of the source population. CONCLUSION: There was no difference in prevalence of or incidence risk for BRSV or BoCV between Swedish OM and CM herds. Because the incidence of herds becoming seropositive was balanced by herds becoming seronegative it should be possible to lower the prevalence of these two infections among Swedish dairy cattle herds if biosecurity is improved. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-014-0091-x) contains supplementary material, which is available to authorized users.",2015 Jan 13,"['Wolff, Cecilia', 'Emanuelson, Ulf', 'Ohlson, Anna', 'Alenius, Stefan', 'Fall, Nils']",Acta Vet Scand,,,True
e56624da7d4f6a86a9cc0a91f3e5a8e98823cea5,PMC,Identification of novel viral receptors with cell line expressing viral receptor-binding protein,http://dx.doi.org/10.1038/srep07935,PMC4300512,25604889,CC BY,"The viral cell receptors and infection can be blocked by the expression of the viral receptor-binding protein. Thus, the viral cell receptor is an attractive target for anti-viral strategies, and the identification of viral cell receptor is critical for better understanding and controlling viral disease. As a model system for viral entry and anti-retroviral approaches, avian sarcoma/leukosis virus (ASLV, including the A-J ten subgroups) has been studied intensively and many milestone discoveries have been achieved based on work with ASLV. Here, we used a DF1 cell line expressed viral receptor-binding protein to efficiently identify chicken Annexin A2 (chANXA2) as a novel receptor for retrovirus ALV-J (avian leukosis virus subgroup J). Our data demonstrate that antibodies or siRNA to chANXA2 significantly inhibited ALV-J infection and replication, and over-expression of chANXA2 permitted the entry of ALV-J into its non-permissible cells. Our findings have not only identified chANXA2 as a novel biomarker for anti-ALV-J, but also demonstrated that cell lines with the expression of viral receptor-binding protein could be as efficient tools for isolating functional receptors to identify novel anti-viral targets.",2015 Jan 21,"['Mei, Mei', 'Ye, Jianqiang', 'Qin, Aijian', 'Wang, Lin', 'Hu, Xuming', 'Qian, Kun', 'Shao, Hongxia']",Sci Rep,,,True
6a45607f711714e68936b74d1af18df649a96b07,PMC,Adverse effects of Influenza A(H1N1)pdm09 virus infection on growth performance of Norwegian pigs - a longitudinal study at a boar testing station,http://dx.doi.org/10.1186/s12917-014-0284-6,PMC4300606,25472551,CC BY,"BACKGROUND: Influenza A(H1N1)pdm09 virus infection in Norwegian pigs was largely subclinical. This study tested the hypothesis that the infection causes negligible impact on pigs’ growth performance in terms of feed conversion efficiency, daily feed intake, daily growth, age on reaching 100 kg bodyweight and overall feed intake. A sample of 1955 pigs originating from 43 breeding herds was classified into five infection status groups; seronegative pigs (n = 887); seropositive pigs (n = 874); pigs positive for virus at bodyweight between 33 kg and 60 kg (n = 123); pigs positive for virus at bodyweight between 61 kg and 80 kg (n = 34) and pigs positive for virus at bodyweight between 81 kg and 100 kg (n = 37). Each pig had daily recordings of feed intake and bodyweight from 33 kg to 100 kg. Marginal effects of the virus infection on the outcomes were estimated by multi-level linear regression, which accounted for known fixed effects (breed, birthdate, average daily feed intake and growth phase) and random effects (cluster effects of pig and herd). RESULTS: The seropositive and virus positive pigs had decreased (P value<0.05) growth performance compared to seronegative pigs even though feed intake was not decreased. Reduced feed conversion efficiency led to lower average daily growth, additional feed requirement and longer time needed to reach the 100 kg bodyweight. The effects were more marked (P value<0.03) in pigs infected at a younger age and lasted a longer period. Despite increased feed intake observed, their growth rates were lower and they took more time to reach 100 kg bodyweight compared to the seronegative pigs. CONCLUSION: Our study rejected the null hypothesis that the virus infection had negligible adverse effects on growth performance of Norwegian pigs.",2014 Dec 4,"['Er, Chiek', 'Lium, Bjørn', 'Tavornpanich, Saraya', 'Hofmo, Peer Ola', 'Forberg, Hilde', 'Hauge, Anna Germundsson', 'Grøntvedt, Carl Andreas', 'Framstad, Tore', 'Brun, Edgar']",BMC Vet Res,,,True
888f3a42d4361d36b3ffbe619427ace11fae0e1b,PMC,"Knowledge and attitude of healthcare workers about middle east respiratory syndrome in multispecialty hospitals of Qassim, Saudi Arabia",http://dx.doi.org/10.1186/1471-2458-14-1281,PMC4300996,25510239,CC BY,"BACKGROUND: With the increase in prevalence of Middle East Respiratory Syndrome (MERS), healthcare workers (HCWs) are at risk of acquiring and subsequently transmitting this lethal virus. In view of this, HCWs were evaluated for their knowledge of and attitude towards MERS in Saudi Arabia. METHODS: A cross sectional study was performed in two hospitals of Qassim region in Saudi Arabia. A total of 280 healthcare workers were selected to participate in this study. Knowledge and attitude were assessed by using self-administered and pretested questionnaire. Descriptive statistics were carried out to express participants’ demographic information, mean knowledge score and mean attitude score of HCWs. Inferential statistics (Mann–Whitney U test and Kruskal Wallis tests, p < 0.05) were used to examine differences between study variables. Chi squares tests were used to assess the association between study variables and attitude questions. Spearman’s rho correlation was used to identify the association between the knowledge, attitude scores. RESULT: Participants demonstrated good knowledge and positive attitude towards MERS. The mean scores of knowledge and attitude were 9.45 ± 1.69 (based on 13 knowledge questions) and 1.82 ± 0.72 (based on 7 attitude questions). The correlation between knowledge and attitude was significant (correlation coefficient: 0.12; P <0.001). HCWs were less educated about the management (42.4%), source (66%) and consequences of MERS (67.3%), while a majority of them were well aware of the hallmark symptoms (96%), precautionary measures (96%) and hygiene issues (94%). Although the majority of respondents showed positive attitude towards the use of protective measures (1.52 ± 0.84), their attitude was negative towards their active participation in infection control program (2.03 ± 0.97). Gender and experience were significantly associated with knowledge and attitude (P < 0.05). CONCLUSIONS: The findings of this study showed that healthcare workers in Qassim region of Saudi Arabia have good knowledge and positive attitude towards MERS. Yet there are areas where low knowledge and negative attitude of HCWs was observed. However, studies are required to assess the knowledge and attitude of HCWs at national level so that effective interventions could be designed as surveillance and infection control measures are critical to global public health.",2014 Dec 16,"['Khan, Muhammad Umair', 'Shah, Shahjahan', 'Ahmad, Akram', 'Fatokun, Omotayo']",BMC Public Health,,,True
4f0e7fc5e32e927fd76e1f5c156cb9caee8eda2a,PMC,Animal board invited review: advances in proteomics for animal and food sciences,http://dx.doi.org/10.1017/S1751731114002602,PMC4301196,25359324,CC BY,"Animal production and health (APH) is an important sector in the world economy, representing a large proportion of the budget of all member states in the European Union and in other continents. APH is a highly competitive sector with a strong emphasis on innovation and, albeit with country to country variations, on scientific research. Proteomics (the study of all proteins present in a given tissue or fluid – i.e. the proteome) has an enormous potential when applied to APH. Nevertheless, for a variety of reasons and in contrast to disciplines such as plant sciences or human biomedicine, such potential is only now being tapped. To counter such limited usage, 6 years ago we created a consortium dedicated to the applications of Proteomics to APH, specifically in the form of a Cooperation in Science and Technology (COST) Action, termed FA1002 – Proteomics in Farm Animals: www.cost-faproteomics.org. In 4 years, the consortium quickly enlarged to a total of 31 countries in Europe, as well as Israel, Argentina, Australia and New Zealand. This article has a triple purpose. First, we aim to provide clear examples on the applications and benefits of the use of proteomics in all aspects related to APH. Second, we provide insights and possibilities on the new trends and objectives for APH proteomics applications and technologies for the years to come. Finally, we provide an overview and balance of the major activities and accomplishments of the COST Action on Farm Animal Proteomics. These include activities such as the organization of seminars, workshops and major scientific conferences, organization of summer schools, financing Short-Term Scientific Missions (STSMs) and the generation of scientific literature. Overall, the Action has attained all of the proposed objectives and has made considerable difference by putting proteomics on the global map for animal and veterinary researchers in general and by contributing significantly to reduce the East–West and North–South gaps existing in the European farm animal research. Future activities of significance in the field of scientific research, involving members of the action, as well as others, will likely be established in the future.",2015 Jan 31,"['Almeida, A. M.', 'Bassols, A.', 'Bendixen, E.', 'Bhide, M.', 'Ceciliani, F.', 'Cristobal, S.', 'Eckersall, P. D.', 'Hollung, K.', 'Lisacek, F.', 'Mazzucchelli, G.', 'McLaughlin, M.', 'Miller, I.', 'Nally, J. E.', 'Plowman, J.', 'Renaut, J.', 'Rodrigues, P.', 'Roncada, P.', 'Staric, J.', 'Turk, R.']",Animal,,,True
d06b1f07cc3e2f1ac0dbcd16995fc351a1bafe91,PMC,Characterizing the Transmission Dynamics and Control of Ebola Virus Disease,http://dx.doi.org/10.1371/journal.pbio.1002057,PMC4301953,25607595,CC0,"Carefully calibrated transmission models have the potential to guide public health officials on the nature and scale of the interventions required to control epidemics. In the context of the ongoing Ebola virus disease (EVD) epidemic in Liberia, Drake and colleagues, in this issue of PLOS Biology, employed an elegant modeling approach to capture the distributions of the number of secondary cases that arise in the community and health care settings in the context of changing population behaviors and increasing hospital capacity. Their findings underscore the role of increasing the rate of safe burials and the fractions of infectious individuals who seek hospitalization together with hospital capacity to achieve epidemic control. However, further modeling efforts of EVD transmission and control in West Africa should utilize the spatial-temporal patterns of spread in the region by incorporating spatial heterogeneity in the transmission process. Detailed datasets are urgently needed to characterize temporal changes in population behaviors, contact networks at different spatial scales, population mobility patterns, adherence to infection control measures in hospital settings, and hospitalization and reporting rates.",2015 Jan 21,"['Chowell, Gerardo', 'Nishiura, Hiroshi']",PLoS Biol,,,True
a401eee90cc270520c65bc001f31a617f4edb7df,PMC,A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus,http://dx.doi.org/10.12688/f1000research.5741.2,PMC4304229,25653841,CC BY,"We are currently faced with a global infectious disease crisis which has been anticipated for decades. While many promising biotherapeutics are being tested, the search for a small molecule has yet to deliver an approved drug or therapeutic for the Ebola or similar filoviruses that cause haemorrhagic fever. Two recent high throughput screens published in 2013 did however identify several hits that progressed to animal studies that are FDA approved drugs used for other indications. The current computational analysis uses these molecules from two different structural classes to construct a common features pharmacophore. This ligand-based pharmacophore implicates a possible common target or mechanism that could be further explored. A recent structure based design project yielded nine co-crystal structures of pyrrolidinone inhibitors bound to the viral protein 35 (VP35). When receptor-ligand pharmacophores based on the analogs of these molecules and the protein structures were constructed, the molecular features partially overlapped with the common features of solely ligand-based pharmacophore models based on FDA approved drugs. These previously identified FDA approved drugs with activity against Ebola were therefore docked into this protein. The antimalarials chloroquine and amodiaquine docked favorably in VP35. We propose that these drugs identified to date as inhibitors of the Ebola virus may be targeting VP35. These computational models may provide preliminary insights into the molecular features that are responsible for their activity against Ebola virus in vitro and in vivo and we propose that this hypothesis could be readily tested.",2014 Dec 12,"['Ekins, Sean', 'Freundlich, Joel S.', 'Coffee, Megan']",F1000Res,,,True
d1eecf25e925b3c331a75d38e687648718e2d4f1,PMC,"A comparison of smartphones to paper-based questionnaires for routine influenza sentinel surveillance, Kenya, 2011–2012",http://dx.doi.org/10.1186/s12911-014-0107-5,PMC4305246,25539745,CC BY,"BACKGROUND: For disease surveillance, manual data collection using paper-based questionnaires can be time consuming and prone to errors. We introduced smartphone data collection to replace paper-based data collection for an influenza sentinel surveillance system in four hospitals in Kenya. We compared the quality, cost and timeliness of data collection between the smartphone data collection system and the paper-based system. METHODS: Since 2006, the Kenya Ministry of Health (MoH) with technical support from the Kenya Medical Research Institute/Centers for Disease Control and Prevention (KEMRI/CDC) conducted hospital-based sentinel surveillance for influenza in Kenya. In May 2011, the MOH replaced paper-based collection with an electronic data collection system using Field Adapted Survey Toolkit (FAST) on HTC Touch Pro2 smartphones at four sentinel sites. We compared 880 paper-based questionnaires dated Jan 2010-Jun 2011 and 880 smartphone questionnaires dated May 2011-Jun 2012 from the four surveillance sites. For each site, we compared the quality, cost and timeliness of each data collection system. RESULTS: Incomplete records were more likely seen in data collected using pen-and-paper compared to data collected using smartphones (adjusted incidence rate ratio (aIRR) 7, 95% CI: 4.4-10.3). Errors and inconsistent answers were also more likely to be seen in data collected using pen-and-paper compared to data collected using smartphones (aIRR: 25, 95% CI: 12.5-51.8). Smartphone data was uploaded into the database in a median time of 7 days while paper-based data took a median of 21 days to be entered (p < 0.01). It cost USD 1,501 (9.4%) more to establish the smartphone data collection system ($17,500) than the pen-and-paper system (USD $15,999). During two years, however, the smartphone data collection system was $3,801 (7%) less expensive to operate ($50,200) when compared to pen-and-paper system ($54,001). CONCLUSIONS: Compared to paper-based data collection, an electronic data collection system produced fewer incomplete data, fewer errors and inconsistent responses and delivered data faster. Although start-up costs were higher, the overall costs of establishing and running the electronic data collection system were lower compared to paper-based data collection system. Electronic data collection using smartphones has potential to improve timeliness, data integrity and reduce costs.",2014 Dec 24,"['Njuguna, Henry N', 'Caselton, Deborah L', 'Arunga, Geoffrey O', 'Emukule, Gideon O', 'Kinyanjui, Dennis K', 'Kalani, Rosalia M', 'Kinkade, Carl', 'Muthoka, Phillip M', 'Katz, Mark A', 'Mott, Joshua A']",BMC Med Inform Decis Mak,,,True
9ac6114492dec5eb4c4afe605b1a83c689df0dec,PMC,Minimal within-host dengue models highlight the specific roles of the immune response in primary and secondary dengue infections,http://dx.doi.org/10.1098/rsif.2014.0886,PMC4305404,25519990,CC BY,"In recent years, the within-host viral dynamics of dengue infections have been increasingly characterized, and the relationship between aspects of these dynamics and the manifestation of severe disease has been increasingly probed. Despite this progress, there are few mathematical models of within-host dengue dynamics, and the ones that exist focus primarily on the general role of immune cells in the clearance of infected cells, while neglecting other components of the immune response in limiting viraemia. Here, by considering a suite of mathematical within-host dengue models of increasing complexity, we aim to isolate the critical components of the innate and the adaptive immune response that suffice in the reproduction of several well-characterized features of primary and secondary dengue infections. By building up from a simple target cell limited model, we show that only the innate immune response is needed to recover the characteristic features of a primary symptomatic dengue infection, while a higher rate of viral infectivity (indicative of antibody-dependent enhancement) and infected cell clearance by T cells are further needed to recover the characteristic features of a secondary dengue infection. We show that these minimal models can reproduce the increased risk of disease associated with secondary heterologous infections that arises as a result of a cytokine storm, and, further, that they are consistent with virological indicators that predict the onset of severe disease, such as the magnitude of peak viraemia, time to peak viral load, and viral clearance rate. Finally, we show that the effectiveness of these virological indicators to predict the onset of severe disease depends on the contribution of T cells in fuelling the cytokine storm.",2015 Feb 6,"['Ben-Shachar, Rotem', 'Koelle, Katia']",J R Soc Interface,,,True
306bedd61bce68752ab0206d35b28c79f4eebb0a,PMC,Minimal within-host dengue models highlight the specific roles of the immune response in primary and secondary dengue infections,http://dx.doi.org/10.1098/rsif.2014.0886,PMC4305404,25519990,CC BY,"In recent years, the within-host viral dynamics of dengue infections have been increasingly characterized, and the relationship between aspects of these dynamics and the manifestation of severe disease has been increasingly probed. Despite this progress, there are few mathematical models of within-host dengue dynamics, and the ones that exist focus primarily on the general role of immune cells in the clearance of infected cells, while neglecting other components of the immune response in limiting viraemia. Here, by considering a suite of mathematical within-host dengue models of increasing complexity, we aim to isolate the critical components of the innate and the adaptive immune response that suffice in the reproduction of several well-characterized features of primary and secondary dengue infections. By building up from a simple target cell limited model, we show that only the innate immune response is needed to recover the characteristic features of a primary symptomatic dengue infection, while a higher rate of viral infectivity (indicative of antibody-dependent enhancement) and infected cell clearance by T cells are further needed to recover the characteristic features of a secondary dengue infection. We show that these minimal models can reproduce the increased risk of disease associated with secondary heterologous infections that arises as a result of a cytokine storm, and, further, that they are consistent with virological indicators that predict the onset of severe disease, such as the magnitude of peak viraemia, time to peak viral load, and viral clearance rate. Finally, we show that the effectiveness of these virological indicators to predict the onset of severe disease depends on the contribution of T cells in fuelling the cytokine storm.",2015 Feb 6,"['Ben-Shachar, Rotem', 'Koelle, Katia']",J R Soc Interface,,,True
49241d35c68b9ffeb0057758abdf00fc18cce2f0,PMC,HIV-1 Replication and the Cellular Eukaryotic Translation Apparatus,http://dx.doi.org/10.3390/v7010199,PMC4306834,25606970,CC BY,"Eukaryotic translation is a complex process composed of three main steps: initiation, elongation, and termination. During infections by RNA- and DNA-viruses, the eukaryotic translation machinery is used to assure optimal viral protein synthesis. Human immunodeficiency virus type I (HIV-1) uses several non-canonical pathways to translate its own proteins, such as leaky scanning, frameshifting, shunt, and cap-independent mechanisms. Moreover, HIV-1 modulates the host translation machinery by targeting key translation factors and overcomes different cellular obstacles that affect protein translation. In this review, we describe how HIV-1 proteins target several components of the eukaryotic translation machinery, which consequently improves viral translation and replication.",2015 Jan 19,"['Guerrero, Santiago', 'Batisse, Julien', 'Libre, Camille', 'Bernacchi, Serena', 'Marquet, Roland', 'Paillart, Jean-Christophe']",Viruses,,,True
12c2a6ee1e3e7cf0f915e5c5454627b7e1ed9db3,PMC,Epimedium koreanum Nakai Displays Broad Spectrum of Antiviral Activity in Vitro and in Vivo by Inducing Cellular Antiviral State,http://dx.doi.org/10.3390/v7010352,PMC4306843,25609307,CC BY,"Epimedium koreanum Nakai has been extensively used in traditional Korean and Chinese medicine to treat a variety of diseases. Despite the plant’s known immune modulatory potential and chemical make-up, scientific information on its antiviral properties and mode of action have not been completely investigated. In this study, the broad antiviral spectrum and mode of action of an aqueous extract from Epimedium koreanum Nakai was evaluated in vitro, and moreover, the protective effect against divergent influenza A subtypes was determined in BALB/c mice. An effective dose of Epimedium koreanum Nakaimarkedly reduced the replication of Influenza A Virus (PR8), Vesicular Stomatitis Virus (VSV), Herpes Simplex Virus (HSV) and Newcastle Disease Virus (NDV) in RAW264.7 and HEK293T cells. Mechanically, we found that an aqueous extract from Epimedium koreanum Nakai induced the secretion of type I IFN and pro-inflammatory cytokines and the subsequent stimulation of the antiviral state in cells. Among various components present in the extract, quercetin was confirmed to have striking antiviral properties. The oral administration of Epimedium koreanum Nakai exhibited preventive effects on BALB/c mice against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2). Therefore, an extract of Epimedium koreanum Nakai and its components play roles as immunomodulators in the innate immune response, and may be potential candidates for prophylactic or therapeutic treatments against diverse viruses in animal and humans.",2015 Jan 20,"['Cho, Won-Kyung', 'Weeratunga, Prasanna', 'Lee, Byeong-Hoon', 'Park, Jun-Seol', 'Kim, Chul-Joong', 'Ma, Jin Yeul', 'Lee, Jong-Soo']",Viruses,,,True
75cf3b144e29ca2e460e2700827543bb72ef0844,PMC,Cluster of Human Infections with Avian Influenza A (H7N9) Cases: A Temporal and Spatial Analysis,http://dx.doi.org/10.3390/ijerph120100816,PMC4306894,25599373,CC BY,"Objectives: This study aims to describe the spatial and temporal characteristics of human infections with H7N9 virus in China using data from February 2013 to March 2014 from the websites of every province’s Population and Family Planning Commission. Methods: A human infection with H7N9 virus dataset was summarized by county to analyze its spatial clustering, and by date of illness onset to analyze its space-time clustering using the ESRI(®) Geographic Information System (GIS) software ArcMap™ 10.1 and SatScan. Results: Based on active surveillance data, the distribution map of H7N9 cases shows that compared to the rest of China, the areas from near the Yangtze River delta (YRD) to farther south around the Pearl River delta (PRD) had the highest densities of H7N9 cases. The case data shows a strong space-time clustering in the areas on and near the YRD from 26 March to 18 April 2013 and a weak space-time clustering only in the areas on and near the PRD between 3 and 4 February 2014. However, for the rest of the study period, H7N9 cases were spatial-temporally randomly distributed. Conclusions: Our results suggested that the spatial-temporal clustering of H7N9 in China between 2013 and 2014 is fundamentally different.",2015 Jan 15,"['Zhang, Yi', 'Shen, Zhixiong', 'Ma, Chunna', 'Jiang, Chengsheng', 'Feng, Cindy', 'Shankar, Nivedita', 'Yang, Peng', 'Sun, Wenjie', 'Wang, Quanyi']",Int J Environ Res Public Health,,,True
57a3e8ebd6f29c8e8126ff652f6f79b1b8fbffc6,PMC,Universal health coverage in ‘One ASEAN’: are migrants included?,http://dx.doi.org/10.3402/gha.v8.25749,PMC4308585,25626624,CC BY,"BACKGROUND: As the Association of South East Asian Nations (ASEAN) gears toward full regional integration by 2015, the cross-border mobility of workers and citizens at large is expected to further intensify in the coming years. While ASEAN member countries have already signed the Declaration on the Protection and Promotion of the Rights of Migrant Workers, the health rights of migrants still need to be addressed, especially with ongoing universal health coverage (UHC) reforms in most ASEAN countries. This paper seeks to examine the inclusion of migrants in the UHC systems of five ASEAN countries which exhibit diverse migration profiles and are currently undergoing varying stages of UHC development. DESIGN: A scoping review of current migration trends and policies as well as ongoing UHC developments and migrant inclusion in UHC in Indonesia, Malaysia, Philippines, Singapore, and Thailand was conducted. RESULTS: In general, all five countries, whether receiving or sending, have schemes that cover migrants to varying extents. Thailand even allows undocumented migrants to opt into its Compulsory Migrant Health Insurance scheme, while Malaysia and Singapore are still yet to consider including migrants in their government-run UHC systems. In terms of predominantly sending countries, the Philippines's social health insurance provides outbound migrants with portable insurance yet with limited benefits, while Indonesia still needs to strengthen the implementation of its compulsory migrant insurance which has a health insurance component. Overall, the five ASEAN countries continue to face implementation challenges, and will need to improve on their UHC design in order to ensure genuine inclusion of migrants, including undocumented migrants. However, such reforms will require strong political decisions from agencies outside the health sector that govern migration and labor policies. Furthermore, countries must engage in multilateral and bilateral dialogue as they redefine UHC beyond the basis of citizenship and reimagine UHC systems that transcend national borders. CONCLUSIONS: By enhancing migrant coverage, ASEAN countries can make UHC systems truly ‘universal’. Migrant inclusion in UHC is a human rights imperative, and it is in ASEAN's best interest to protect the health of migrants as it pursues the path toward collective social progress and regional economic prosperity.",2015 Jan 24,"['Guinto, Ramon Lorenzo Luis R.', 'Curran, Ufara Zuwasti', 'Suphanchaimat, Rapeepong', 'Pocock, Nicola S.']",Glob Health Action,,,True
9b4e7443a59fb1fd764f172bd67a0f73da1ec3cd,PMC,Qualitative and Quantitative Analysis of the Major Constituents in Chinese Medical Preparation Lianhua-Qingwen Capsule by UPLC-DAD-QTOF-MS,http://dx.doi.org/10.1155/2015/731765,PMC4308632,25654135,CC BY,"Lianhua-Qingwen capsule (LQC) is a commonly used Chinese medical preparation to treat viral influenza and especially played a very important role in the fight against severe acute respiratory syndrome (SARS) in 2002-2003 in China. In this paper, a rapid ultraperformance liquid chromatography coupled with diode-array detector and quadrupole time-of-flight mass spectrometry (UPLC-DAD-QTOF-MS) method was established for qualitative and quantitative analysis of the major constituents of LQC. A total of 61 compounds including flavonoids, phenylpropanoids, anthraquinones, triterpenoids, iridoids, and other types of compounds were unambiguously or tentatively identified by comparing the retention times and accurate mass measurement with reference compounds or literature data. Among them, twelve representative compounds were further quantified as chemical markers in quantitative analysis, including salidroside, chlorogenic acid, forsythoside E, cryptochlorogenic acid, amygdalin, sweroside, hyperin, rutin, forsythoside A, phillyrin, rhein, and glycyrrhizic acid. The UPLC-DAD method was evaluated with linearity, limit of detection (LOD), limit of quantification (LOQ), precision, stability, repeatability, and recovery tests. The results showed that the developed quantitative method was linear, sensitive, and precise for the quality control of LQC.",2015 Jan 8,"['Jia, Weina', 'Wang, Chunhua', 'Wang, Yuefei', 'Pan, Guixiang', 'Jiang, Miaomiao', 'Li, Zheng', 'Zhu, Yan']",ScientificWorldJournal,,,True
ed5375ac7d887e311e407121b4c80e8d0ca0afed,PMC,The RNA shapes studio,http://dx.doi.org/10.1093/bioinformatics/btu649,PMC4308662,25273103,CC BY,"Motivation: Abstract shape analysis, first proposed in 2004, allows one to extract several relevant structures from the folding space of an RNA sequence, preferable to focusing in a single structure of minimal free energy. We report recent extensions to this approach. Results: We have rebuilt the original RNAshapes as a repository of components that allows us to integrate several established tools for RNA structure analysis: RNAshapes, RNAalishapes and pknotsRG, including its recent extension pKiss. As a spin-off, we obtain heretofore unavailable functionality: e. g. with pKiss, we can now perform abstract shape analysis for structures holding pseudoknots up to the complexity of kissing hairpin motifs. The new tool pAliKiss can predict kissing hairpin motifs from aligned sequences. Along with the integration, the functionality of the tools was also extended in manifold ways. Availability and implementation: As before, the tool is available on the Bielefeld Bioinformatics server at http://bibiserv.cebitec.uni-bielefeld.de/rnashapesstudio. Contact: bibi-help@cebitec.uni-bielefeld.de",2015 Feb 1,"['Janssen, Stefan', 'Giegerich, Robert']",Bioinformatics,,,True
21fd38266c7336a6ace6ca87ee9ac07a580cfdeb,PMC,Comparative Analysis of the Intestinal Bacterial and RNA Viral Communities from Sentinel Birds Placed on Selected Broiler Chicken Farms,http://dx.doi.org/10.1371/journal.pone.0117210,PMC4311960,25635690,CC0,"There is a great deal of interest in characterizing the complex microbial communities in the poultry gut, and in understanding the effects of these dynamic communities on poultry performance, disease status, animal welfare, and microbes with human health significance. Investigations characterizing the poultry enteric virome have identified novel poultry viruses, but the roles these viruses play in disease and performance problems have yet to be fully characterized. The complex bacterial community present in the poultry gut influences gut development, immune status, and animal health, each of which can be an indicator of overall performance. The present metagenomic investigation was undertaken to provide insight into the colonization of specific pathogen free chickens by enteric microorganisms under field conditions and to compare the pre-contact intestinal microbiome with the altered microbiome following contact with poultry raised in the field. Analysis of the intestinal virome from contact birds (“sentinels”) placed on farms revealed colonization by members of the Picornaviridae, Picobirnaviridae, Reoviridae, and Astroviridae that were not present in pre-contact birds or present in proportionally lower numbers. Analysis of the sentinel gut bacterial community revealed an altered community in the post-contact birds, notably by members of the Lachnospiracea/Clostridium and Lactobacillus families and genera. Members of the avian enteric Reoviridae and Astroviridae have been well-characterized and have historically been implicated in poultry enteric disease; members of the Picobirnaviridae and Picornaviridae have only relatively recently been described in the poultry and avian gut, and their roles in the recognized disease syndromes and in poultry performance in general have not been determined. This metagenomic analysis has provided insight into the colonization of the poultry gut by enteric microbes circulating in commercial broiler flocks, and has identified enteric viruses and virus communities that warrant further study in order to understand their role(s) in avian gut health and disease.",2015 Jan 30,"['Day, J. Michael', 'Oakley, Brian B.', 'Seal, Bruce S.', 'Zsak, Laszlo']",PLoS One,,,True
9bad9c5864165815b35dd2c78cd0ed7b285f0517,PMC,Receptor Binding Domain Based HIV Vaccines,http://dx.doi.org/10.1155/2015/594109,PMC4312573,25667925,CC BY,"This paper analyzes the main trend of the development of acquired immunodeficiency syndrome (AIDS) vaccines in recent years. Designing an HIV-1 vaccine that provides robust protection from HIV-1 infection remains a challenge despite many years of effort. Therefore, we describe the receptor binding domain of gp120 as a target for developing AIDS vaccines. And we recommend some measures that could induce efficiently and produce cross-reactive neutralizing antibodies with high binding affinity. Those measures may offer a new way of the research and development of the potent and broad AIDS vaccines.",2015 Jan 15,"['Liu, Huan', 'Bi, Wenwen', 'Wang, Qian', 'Lu, Lu', 'Jiang, Shibo']",Biomed Res Int,,,True
396b05e6ede13dc6078ddf0eae5c14ceae695600,PMC,Annexin A2 as a target endothelial cell membrane autoantigen in Behçet's disease,http://dx.doi.org/10.1038/srep08162,PMC4313095,25641213,CC BY,"Cell membrane proteins are believed to play a critical role in the pathogenesis of autoimmune diseases. However, few membrane autoantigens have been linked with Behçet's disease. Here, a cell-chip was performed to identify autoantibody target cells, and the suspected autoantigens were detected using immunoblotting. The amino acid sequences of the detected proteins were determined using LC-MALDI-TOF/TOF. Putative proteins were recombinantly expressed and purified, and a corresponding ELISA was developed and clinically validated using real clinical samples. It was found that a 36-kDa membrane protein - annexin A2 - was detected in approximately one-third of the patients' blood circulation. The immunohistochemistry results showed that annexin A2 was highly expressed in vascular endothelial cells. Moreover, vascular involvement was significantly higher in the anti-annexin A2 antibody-positive group versus the anti-annexin A2 antibody-negative group among all the clinical samples analyzed, indicating that annexin A2 is a novel endothelial cell membrane antigen involved in Behçet's disease.",2015 Feb 2,"['Chen, Peng', 'Yan, Hai', 'Tian, Yaping', 'Xun, Yiping', 'Shi, Lili', 'Bao, Ran', 'Zhang, Huai', 'Chen, Guangyu', 'Yang, Chunhe', 'Sun, Shutao', 'Wang, Yajie', 'Liu, Li', 'Zhou, Yabin', 'Zhang, Chunyan', 'Wang, Xiaoxu', 'Wen, Yongqiang', 'Bian, Yongzhong', 'Du, Hongwu']",Sci Rep,,,True
7992401d6ef4c8a20818079438362577895f25b7,PMC,Biosecurity and Dual-Use Research: Gaining Function – But at What Cost?,http://dx.doi.org/10.3389/fpubh.2015.00013,PMC4313596,25699244,CC BY,,2015 Feb 2,"['Vogel, Kathleen M.', 'Ozin, Amanda J.', 'Suk, Jonathan E.']",Front Public Health,,,True
238d2be0d4db41b5460bd3a50a0a374549c189aa,PMC,Houttuynia cordata Targets the Beginning Stage of Herpes Simplex Virus Infection,http://dx.doi.org/10.1371/journal.pone.0115475,PMC4314066,25643242,CC BY,"Herpes simplex virus (HSV), a common latent virus in humans, causes certain severe diseases. Extensive use of acyclovir (ACV) results in the development of drug-resistant HSV strains, hence, there is an urgent need to develop new drugs to treat HSV infection. Houttuynia cordata (H. cordata), a natural herbal medicine, has been reported to exhibit anti-HSV effects which is partly NF-κB-dependent. However, the molecular mechanisms by which H. cordata inhibits HSV infection are not elucidated thoroughly. Here, we report that H. cordata water extracts (HCWEs) inhibit the infection of HSV-1, HSV-2, and acyclovir-resistant HSV-1 mainly via blocking viral binding and penetration in the beginning of infection. HCWEs also suppress HSV replication. Furthermore, HCWEs attenuate the first-wave of NF-κB activation, which is essential for viral gene expressions. Further analysis of six compounds in HCWEs revealed that quercetin and isoquercitrin inhibit NF-κB activation and additionally, quercetin also has an inhibitory effect on viral entry. These results indicate that HCWEs can inhibit HSV infection through multiple mechanisms and could be a potential lead for development of new drugs for treating HSV.",2015 Feb 2,"['Hung, Pei-Yun', 'Ho, Bing-Ching', 'Lee, Szu-Yuan', 'Chang, Sui-Yuan', 'Kao, Chuan-Liang', 'Lee, Shoei-Sheng', 'Lee, Chun-Nan']",PLoS One,,,True
66309c65612bed65732f79f347693a170e10e1f8,PMC,Angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas axis prevents lipopolysaccharide–induced apoptosis of pulmonary microvascular endothelial cells by inhibiting JNK/NF–κB pathways,http://dx.doi.org/10.1038/srep08209,PMC4314638,25644821,CC BY,"ACE2 and Ang–(1–7) have important roles in preventing acute lung injury. However, it is not clear whether upregulation of the ACE2/Ang–(1–7)/Mas axis prevents LPS–induced injury in pulmonary microvascular endothelial cells (PMVECs) by inhibiting the MAPKs/NF–κB pathways. Primary cultured rat PMVECs were transduced with lentiviral–borne Ace2 or shRNA–Ace2, and then treated or not with Mas receptor blocker (A779) before exposure to LPS. LPS stimulation resulted in the higher levels of AngII, Ang–(1–7), cytokine secretion, and apoptosis rates, and the lower ACE2/ACE ratio. Ace2 reversed the ACE2/ACE imbalance and increased Ang–(1–7) levels, thus reducing LPS–induced apoptosis and inflammation, while inhibition of Ace2 reversed all these effects. A779 abolished these protective effects of Ace2. LPS treatment was associated with activation of the ERK, p38, JNK, and NF–κB pathways, which were aggravated by A779. Pretreatment with A779 prevented the Ace2–induced blockade of p38, JNK, and NF–κB phosphorylation. However, only JNK inhibitor markedly reduced apoptosis and cytokine secretion in PMVECs with Ace2 deletion and A779 pretreatment. These results suggest that the ACE2/Ang–(1–7)/Mas axis has a crucial role in preventing LPS–induced apoptosis and inflammation of PMVECs, by inhibiting the JNK/NF–κB pathways.",2015 Feb 3,"['Li, Yingchuan', 'Cao, Yongmei', 'Zeng, Zhen', 'Liang, Mengfan', 'Xue, Ying', 'Xi, Caihua', 'Zhou, Ming', 'Jiang, Wei']",Sci Rep,,,True
b4662fd83b035e7eb06014924a4a03c854ad797f,PMC,Exploration of diarrhoea seasonality and its drivers in China,http://dx.doi.org/10.1038/srep08241,PMC4316158,25649629,CC BY,"This study investigated the diarrhoea seasonality and its potential drivers as well as potential opportunities for future diarrhoea control and prevention in China. Data on weekly infectious diarrhoea cases in 31 provinces of China from 2005 to 2012, and data on demographic and geographic characteristics, as well as climatic factors, were complied. A cosinor function combined with a Poisson regression was used to calculate the three seasonal parameters of diarrhoea in different provinces. Regression tree analysis was used to identify the predictors of diarrhoea seasonality. Diarrhoea cases in China showed a bimodal distribution. Diarrhoea in children <5 years was more likely to peak in fall-winter seasons, while diarrhoea in persons > = 5 years peaked in summer. Latitude was significantly associated with spatial pattern of diarrhoea seasonality, with peak and trough times occurring earlier at high latitudes (northern areas), and later at low latitudes (southern areas). The annual amplitudes of diarrhoea in persons > = 5 years increased with latitude (r = 0.62, P<0.001). Latitude 27.8° N and 38.65° N were the latitudinal thresholds for diarrhoea seasonality in China. Regional-specific diarrhoea control and prevention strategies may be optimal for China. More attention should be paid to diarrhoea in children <5 years during fall-winter seasons.",2015 Feb 4,"['Xu, Zhiwei', 'Hu, Wenbiao', 'Zhang, Yewu', 'Wang, Xiaofeng', 'Zhou, Maigeng', 'Su, Hong', 'Huang, Cunrui', 'Tong, Shilu', 'Guo, Qing']",Sci Rep,,,True
6151f96019df6ea8cba1f74c423f9dd6f1e0ec02,PMC,Exploration of diarrhoea seasonality and its drivers in China,http://dx.doi.org/10.1038/srep08241,PMC4316158,25649629,CC BY,"This study investigated the diarrhoea seasonality and its potential drivers as well as potential opportunities for future diarrhoea control and prevention in China. Data on weekly infectious diarrhoea cases in 31 provinces of China from 2005 to 2012, and data on demographic and geographic characteristics, as well as climatic factors, were complied. A cosinor function combined with a Poisson regression was used to calculate the three seasonal parameters of diarrhoea in different provinces. Regression tree analysis was used to identify the predictors of diarrhoea seasonality. Diarrhoea cases in China showed a bimodal distribution. Diarrhoea in children <5 years was more likely to peak in fall-winter seasons, while diarrhoea in persons > = 5 years peaked in summer. Latitude was significantly associated with spatial pattern of diarrhoea seasonality, with peak and trough times occurring earlier at high latitudes (northern areas), and later at low latitudes (southern areas). The annual amplitudes of diarrhoea in persons > = 5 years increased with latitude (r = 0.62, P<0.001). Latitude 27.8° N and 38.65° N were the latitudinal thresholds for diarrhoea seasonality in China. Regional-specific diarrhoea control and prevention strategies may be optimal for China. More attention should be paid to diarrhoea in children <5 years during fall-winter seasons.",2015 Feb 4,"['Xu, Zhiwei', 'Hu, Wenbiao', 'Zhang, Yewu', 'Wang, Xiaofeng', 'Zhou, Maigeng', 'Su, Hong', 'Huang, Cunrui', 'Tong, Shilu', 'Guo, Qing']",Sci Rep,,,False
4c452cc6bb3cb81575f11749b5fb5e5206d6836e,PMC,A confirmed severe case of human infection with avian-origin influenza H7N9: A case report,http://dx.doi.org/10.3892/etm.2014.2159,PMC4316893,25667615,CC BY,"A male patient, aged 77 years, was admitted to hospital with the chief complaint of persistent hyperpyrexia that had presented for four days. The patient also suffered from hypoxemia, and a large white shadow in the left lung was observed on a chest radiograph, indicating inflammation. No therapeutic effect was observed with anti-infection treatment. The patient admitted a history of direct contact with live chickens two weeks prior to hospital admission. The day after admission to the Jingnan District Centre Hospital of Shanghai (Shanghai, China), the patient was diagnosed with severe H7N9 avian influenza infection by nasopharyngeal swab and blood sampling detection. Although the patient received anti-infective drugs, intubated assisted ventilation and circulation support, the condition of the patient continued to rapidly deteriorate. Oxygen saturation decreased and gastrointestinal bleeding occurred, with the body temperature fluctuating between 39 and 40°C. By day 6 after admission, the patient presented with circulatory failure, with liver and renal failure. On day 7, the blood pressure of the patient was unable to be measured, and the patient was diagnosed with multiple organ dysfunction. Subsequently, clinical death was declared with the patient exhibiting asystole and no spontaneous breathing.",2015 Mar 30,"['CAO, HUI-FANG', 'LIANG, ZHONG-HUI', 'FENG, YING', 'ZHANG, ZI-NAN', 'XU, JING', 'HE, HE']",Exp Ther Med,,,True
77888e24fe540edda3d9cd2e0aadd2e699aa466d,PMC,On the Dark Side of Therapies with Immunoglobulin Concentrates: The Adverse Events,http://dx.doi.org/10.3389/fimmu.2015.00011,PMC4318428,25699039,CC BY,"Therapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE) profile of IgG concentrates which is, even at life-long need for therapy, excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current good manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times, the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below, we review elements of non-infectious AEs, and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates.",2015 Feb 5,"['Späth, Peter J.', 'Granata, Guido', 'La Marra, Fabiola', 'Kuijpers, Taco W.', 'Quinti, Isabella']",Front Immunol,,,True
9a31e63c4ec26320695ef383dfd8c772d6afc92b,PMC,Mass fatality preparedness among medical examiners/coroners in the United States: a cross-sectional study,http://dx.doi.org/10.1186/1471-2458-14-1275,PMC4320632,25511819,CC BY,"BACKGROUND: In the United States (US), Medical Examiners and Coroners (ME/Cs) have the legal authority for the management of mass fatality incidents (MFI). Yet, preparedness and operational capabilities in this sector remain largely unknown. The purpose of this study was twofold; first, to identify appropriate measures of preparedness, and second, to assess preparedness levels and factors significantly associated with preparedness. METHODS: Three separate checklists were developed to measure different aspects of preparedness: MFI Plan Elements, Operational Capabilities, and Pre-existing Resource Networks. Using a cross-sectional study design, data on these and other variables of interest were collected in 2014 from a national convenience sample of ME/C using an internet-based, anonymous survey. Preparedness levels were determined and compared across Federal Regions and in relation to the number of Presidential Disaster Declarations, also by Federal Region. Bivariate logistic and multivariable models estimated the associations between organizational characteristics and relative preparedness. RESULTS: A large proportion (42%) of respondents reported that less than 25 additional fatalities over a 48-hour period would exceed their response capacities. The preparedness constructs measured three related, yet distinct, aspects of preparedness, with scores highly variable and generally suboptimal. Median scores for the three preparedness measures also varied across Federal Regions and as compared to the number of Presidential Declared Disasters, also by Federal Region. Capacity was especially limited for activating missing persons call centers, launching public communications, especially via social media, and identifying temporary interment sites. The provision of staff training was the only factor studied that was significantly (positively) associated (p < .05) with all three preparedness measures. Although ME/Cs ranked local partners, such as Offices of Emergency Management, first responders, and funeral homes, as the most important sources of assistance, a sizeable proportion (72%) expected federal assistance. CONCLUSIONS: The three measures of MFI preparedness allowed for a broad and comprehensive assessment of preparedness. In the future, these measures can serve as useful benchmarks or criteria for assessing ME/Cs preparedness. The study findings suggest multiple opportunities for improvement, including the development and implementation of national strategies to ensure uniform standards for MFI management across all jurisdictions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2458-14-1275) contains supplementary material, which is available to authorized users.",2014 Dec 15,"['Gershon, Robyn RM', 'Orr, Mark G', 'Zhi, Qi', 'Merrill, Jacqueline A', 'Chen, Daniel Y', 'Riley, Halley EM', 'Sherman, Martin F']",BMC Public Health,,,True
e68bb0f18492dc5645e027d5da3369ed17edbabd,PMC,Mass fatality preparedness among medical examiners/coroners in the United States: a cross-sectional study,http://dx.doi.org/10.1186/1471-2458-14-1275,PMC4320632,25511819,CC BY,"BACKGROUND: In the United States (US), Medical Examiners and Coroners (ME/Cs) have the legal authority for the management of mass fatality incidents (MFI). Yet, preparedness and operational capabilities in this sector remain largely unknown. The purpose of this study was twofold; first, to identify appropriate measures of preparedness, and second, to assess preparedness levels and factors significantly associated with preparedness. METHODS: Three separate checklists were developed to measure different aspects of preparedness: MFI Plan Elements, Operational Capabilities, and Pre-existing Resource Networks. Using a cross-sectional study design, data on these and other variables of interest were collected in 2014 from a national convenience sample of ME/C using an internet-based, anonymous survey. Preparedness levels were determined and compared across Federal Regions and in relation to the number of Presidential Disaster Declarations, also by Federal Region. Bivariate logistic and multivariable models estimated the associations between organizational characteristics and relative preparedness. RESULTS: A large proportion (42%) of respondents reported that less than 25 additional fatalities over a 48-hour period would exceed their response capacities. The preparedness constructs measured three related, yet distinct, aspects of preparedness, with scores highly variable and generally suboptimal. Median scores for the three preparedness measures also varied across Federal Regions and as compared to the number of Presidential Declared Disasters, also by Federal Region. Capacity was especially limited for activating missing persons call centers, launching public communications, especially via social media, and identifying temporary interment sites. The provision of staff training was the only factor studied that was significantly (positively) associated (p < .05) with all three preparedness measures. Although ME/Cs ranked local partners, such as Offices of Emergency Management, first responders, and funeral homes, as the most important sources of assistance, a sizeable proportion (72%) expected federal assistance. CONCLUSIONS: The three measures of MFI preparedness allowed for a broad and comprehensive assessment of preparedness. In the future, these measures can serve as useful benchmarks or criteria for assessing ME/Cs preparedness. The study findings suggest multiple opportunities for improvement, including the development and implementation of national strategies to ensure uniform standards for MFI management across all jurisdictions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2458-14-1275) contains supplementary material, which is available to authorized users.",2014 Dec 15,"['Gershon, Robyn RM', 'Orr, Mark G', 'Zhi, Qi', 'Merrill, Jacqueline A', 'Chen, Daniel Y', 'Riley, Halley EM', 'Sherman, Martin F']",BMC Public Health,,,True
f0e6cef57dbae030aea2f324e21e00945ac659cf,PMC,In Vitro Bactericidal Activity of 4- and 5-Chloro-2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides against MRSA,http://dx.doi.org/10.1155/2015/349534,PMC4321674,25692135,CC BY,"A series of nine substituted 2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides was assessed as prospective bactericidal agents against three clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus ATCC 29213 as the reference and quality control strain. The minimum bactericidal concentration was determined by subculturing aliquots from MIC determination onto substance-free agar plates. The bactericidal kinetics of compounds 5-chloro-2-hydroxy-N-[(2S)-3-methyl-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino}butan-2-yl]benzamide (1f), N-{(2S)-1-[(4-bromophenyl)amino]-3-methyl-1-oxobutan-2-yl}-4-chloro-2-hydroxybenzamide (1g), and 4-chloro-N-{(2S)-1-[(3,4-dichlorophenyl)amino]-3-methyl-1-oxobutan-2-yl}-2-hydroxybenzamide (1h) was established by time-kill assay with a final concentration of the compound equal to 1x, 2x, and 4x MIC; aliquots were removed at 0, 4, 6, 8, and 24 h time points. The most potent bactericidal agent was compound 1f exhibiting remarkable rapid concentration-dependent bactericidal effect even at 2x MIC at 4, 6, and 8 h (with a reduction in bacterial count ranging from 3.08 to 3.75 log(10) CFU/mL) and at 4x MIC at 4, 6, 8, and 24 h (5.30 log(10) CFU/mL reduction in bacterial count) after incubation against MRSA 63718. Reliable bactericidal effect against other strains was maintained at 4x MIC at 24 h.",2015 Jan 15,"['Zadrazilova, Iveta', 'Pospisilova, Sarka', 'Pauk, Karel', 'Imramovsky, Ales', 'Vinsova, Jarmila', 'Cizek, Alois', 'Jampilek, Josef']",Biomed Res Int,,,True
77779295f3fcc05a193b349478b8730b226790c7,PMC,"Public, environmental, and occupational health research activity in Arab countries: bibliometric, citation, and collaboration analysis",http://dx.doi.org/10.1186/2049-3258-73-1,PMC4322552,25671116,CC BY,"BACKGROUND: The objective of this study was to analyze quantity, assess quality, and investigate international collaboration in research from Arab countries in the field of public, environmental and occupational health. METHODS: Original scientific articles and reviews published from the 22 Arab countries in the category ""public, environmental & occupational health"" during the study period (1900 – 2012) were screened using the ISI Web of Science database. RESULTS: The total number of original and review research articles published in the category of ""public, environmental & occupational health"" from Arab countries was 4673. Main area of research was tropical medicine (1862; 39.85%). Egypt with 1200 documents (25.86%) ranked first in quantity and ranked first in quality of publications (h-index = 51). The study identified 2036 (43.57%) documents with international collaboration. Arab countries actively collaborated with authors in Western Europe (22.91%) and North America (21.04%). Most of the documents (79.9%) were published in public health related journals while 21% of the documents were published in journals pertaining to prevention medicine, environmental, occupational health and epidemiology. CONCLUSION: Research in public, environmental and occupational health in Arab countries is in the rise. Public health research was dominant while environmental and occupation health research was relatively low. International collaboration was a good tool for increasing research quantity and quality.",2015 Jan 5,"['Sweileh, Waleed M', 'Zyoud, Sa’ed H', 'Al-Jabi, Samah W', 'Sawalha, Ansam F']",Arch Public Health,,,True
bbc0322ac1427ea61ca213645a219daf5bd9d5ac,PMC,Spatial pattern of severe acute respiratory syndrome in-out flow in 2003 in Mainland China,http://dx.doi.org/10.1186/s12879-014-0721-y,PMC4322810,25551367,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS) spread to 32 countries and regions within a few months in 2003. There were 5327 SARS cases from November 2002 to May 2003 in Mainland China, which involved 29 provinces, resulted in 349 deaths, and directly caused economic losses of $18.3 billion. METHODS: This study used an in-out flow model and flow mapping to visualize and explore the spatial pattern of SARS transmission in different regions. In-out flow is measured by the in-out degree and clustering coefficient of SARS. Flow mapping is an exploratory method of spatial visualization for interaction data. RESULTS: The findings were as follows. (1) SARS in-out flow had a clear hierarchy. It formed two main centers, Guangdong in South China and Beijing in North China, and two secondary centers, Shanxi and Inner Mongolia, both connected to Beijing. (2) “Spring Festival travel” strengthened external flow, but “SARS panic effect” played a more significant role and pushed the external flow to the peak. (3) External flow and its three typical kinds showed obvious spatial heterogeneity, such as self-spreading flow (spatial displacement of SARS cases only within the province or municipality of onset and medical locations); hospitalized flow (spatial displacement of SARS cases that had been seen by a hospital doctor); and migrant flow (spatial displacement of SARS cases among migrant workers). (4) Internal and external flow tended to occur in younger groups, and occupational differentiation was particularly evident. Low-income groups of male migrants aged 19–35 years were the main routes of external flow. CONCLUSIONS: During 2002–2003, SARS in-out flow played an important role in countrywide transmission of the disease in Mainland China. The flow had obvious spatial heterogeneity, which was influenced by migrants’ behavior characteristics. In addition, the Chinese holiday effect led to irregular spread of SARS, but the panic effect was more apparent in the middle and late stages of the epidemic. These findings constitute valuable input to prevent and control future serious infectious diseases like SARS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0721-y) contains supplementary material, which is available to authorized users.",2014 Dec 31,"['Xu, Chengdong', 'Wang, Jinfeng', 'Wang, Li', 'Cao, Chunxiang']",BMC Infect Dis,,,True
900c4d81fe0fb7de36ec0235be6e2e873984ec08,PMC,An integrative approach to enhancing small-scale poultry slaughterhouses by addressing regulations and food safety in northern -Thailand,http://dx.doi.org/10.1186/2049-9957-3-46,PMC4322817,25671124,CC BY,"BACKGROUND: In Asian countries, small-scale rural poultry meat production can face challenges due to food safety policies that limit economic growth and hinder improvement of sanitation and disease prevention. In this study, an integrative, participatory research approach was used to elucidate the sanitation and disease prevention practices in small-scale poultry slaughterhouses in rural northern Thailand. METHODS: Initial steps included the identification of key stakeholders associated with the meat production chain, development of a research framework, and design of a methodology based on stakeholder consultations. The framework and methodology combine issues in five major areas: (1) public health, (2) socioeconomics, (3) policy, (4) veterinary medicine, and (5) communities and the environment. Methods used include questionnaires, direct observation, focus groups, and in-depth interviews. In addition, a microbiological risk assessment approach was employed to detect Salmonella contamination in meat processing facilities. The microbial risk assessment was combined with stakeholder perceptions to provide an overview of the existing situation, as well as to identify opportunities for upgrading slaughterhouses in order to more effectively address matters of food safety, processing, and government licensing. RESULTS: The conceptual framework developed elucidated the complex factors limiting small-scale slaughterhouse improvement including a lack of appropriate enabling policies and an apparent absence of feasible interventions for improvement. Unhygienic slaughterhouse management was reflected in the incidence of Salmonella contamination in both the meat and the surrounding environment. CONCLUSION: There is potential for the use of an integrative approach to address critical problems at the interface of rural development and public health. The findings of this study could serve as a model for transdisciplinary studies and interventions related to other similar complex challenges. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-3-46) contains supplementary material, which is available to authorized users.",2014 Dec 5,"['Chotinun, Suwit', 'Rojanasthien, Suvichai', 'Unger, Fred', 'Suwan, Manat', 'Tadee, Pakpoom', 'Patchanee, Prapas']",Infect Dis Poverty,,,False
41472dcd6a621cee86ccbeedd2fc0f7ae93be71b,PMC,An integrative approach to enhancing small-scale poultry slaughterhouses by addressing regulations and food safety in northern -Thailand,http://dx.doi.org/10.1186/2049-9957-3-46,PMC4322817,25671124,CC BY,"BACKGROUND: In Asian countries, small-scale rural poultry meat production can face challenges due to food safety policies that limit economic growth and hinder improvement of sanitation and disease prevention. In this study, an integrative, participatory research approach was used to elucidate the sanitation and disease prevention practices in small-scale poultry slaughterhouses in rural northern Thailand. METHODS: Initial steps included the identification of key stakeholders associated with the meat production chain, development of a research framework, and design of a methodology based on stakeholder consultations. The framework and methodology combine issues in five major areas: (1) public health, (2) socioeconomics, (3) policy, (4) veterinary medicine, and (5) communities and the environment. Methods used include questionnaires, direct observation, focus groups, and in-depth interviews. In addition, a microbiological risk assessment approach was employed to detect Salmonella contamination in meat processing facilities. The microbial risk assessment was combined with stakeholder perceptions to provide an overview of the existing situation, as well as to identify opportunities for upgrading slaughterhouses in order to more effectively address matters of food safety, processing, and government licensing. RESULTS: The conceptual framework developed elucidated the complex factors limiting small-scale slaughterhouse improvement including a lack of appropriate enabling policies and an apparent absence of feasible interventions for improvement. Unhygienic slaughterhouse management was reflected in the incidence of Salmonella contamination in both the meat and the surrounding environment. CONCLUSION: There is potential for the use of an integrative approach to address critical problems at the interface of rural development and public health. The findings of this study could serve as a model for transdisciplinary studies and interventions related to other similar complex challenges. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-3-46) contains supplementary material, which is available to authorized users.",2014 Dec 5,"['Chotinun, Suwit', 'Rojanasthien, Suvichai', 'Unger, Fred', 'Suwan, Manat', 'Tadee, Pakpoom', 'Patchanee, Prapas']",Infect Dis Poverty,,,True
7b757b4f7e7148f6899ee9c7ae849ff653471a76,PMC,Generation of Human B-Cell Lines Dependent on CD40-Ligation and Interleukin-4,http://dx.doi.org/10.3389/fimmu.2015.00055,PMC4324153,25717328,CC BY,,2015 Feb 11,"Banchereau, Jacques",Front Immunol,,,True
def339c1e20c36c30ae665e0a4573ed30be45df7,PMC,Nelfinavir Impairs Glycosylation of Herpes Simplex Virus 1 Envelope Proteins and Blocks Virus Maturation,http://dx.doi.org/10.1155/2015/687162,PMC4325974,25709648,CC BY,"Nelfinavir (NFV) is an HIV-1 aspartyl protease inhibitor that has numerous effects on human cells, which impart attractive antitumor properties. NFV has also been shown to have in vitro inhibitory activity against human herpesviruses (HHVs). Given the apparent absence of an aspartyl protease encoded by HHVs, we investigated the mechanism of action of NFV herpes simplex virus type 1 (HSV-1) in cultured cells. Selection of HSV-1 resistance to NFV was not achieved despite multiple passages under drug pressure. NFV did not significantly affect the level of expression of late HSV-1 gene products. Normal numbers of viral particles appeared to be produced in NFV-treated cells by electron microscopy but remain within the cytoplasm more often than controls. NFV did not inhibit the activity of the HSV-1 serine protease nor could its antiviral activity be attributed to inhibition of Akt phosphorylation. NFV was found to decrease glycosylation of viral glycoproteins B and C and resulted in aberrant subcellular localization, consistent with induction of endoplasmic reticulum stress and the unfolded protein response by NFV. These results demonstrate that NFV causes alterations in HSV-1 glycoprotein maturation and egress and likely acts on one or more host cell functions that are important for HHV replication.",2015 Jan 29,"['Gantt, Soren', 'Gachelet, Eliora', 'Carlsson, Jacquelyn', 'Barcy, Serge', 'Casper, Corey', 'Lagunoff, Michael']",Adv Virol,,,True
836ec77a81730c540b750253cc4ee9f8fed0fb49,PMC,Conformational B-Cell Epitope Prediction Method Based on Antigen Preprocessing and Mimotopes Analysis,http://dx.doi.org/10.1155/2015/257030,PMC4326220,25705652,CC BY,"Identification of epitopes which invokes strong humoral responses is an essential issue in the field of immunology. Various computational methods that have been developed based on the antigen structures and the mimotopes these years narrow the search for experimental validation. These methods can be divided into two categories: antigen structure-based methods and mimotope-based methods. Though new methods of the two kinds have been proposed in these years, they cannot maintain a high degree of satisfaction in various circumstances. In this paper, we proposed a new conformational B-cell epitope prediction method based on antigen preprocessing and mimotopes analysis. The method classifies the antigen surface residues into “epitopes” and “nonepitopes” by six epitope propensity scales, removing the “nonepitopes” and using the preprocessed antigen for epitope prediction based on mimotope sequences. The proposed method gives out the mean F score of 0.42 on the testing dataset. When compared with other publicly available servers by using the testing dataset, the new method yields better performance. The results demonstrate the proposed method is competent for the conformational B-cell epitope prediction.",2015 Jan 29,"['Sun, Pingping', 'Ju, Haixu', 'Zhang, Baowen', 'Gu, Yu', 'Liu, Bo', 'Huang, Yanxin', 'Zhang, Huijie', 'Li, Yuxin']",Biomed Res Int,,,True
b86e6acc419df7b1fd637a785834a84b59f4f9c5,PMC,Online health information – what the newspapers tell their readers: a systematic content analysis,http://dx.doi.org/10.1186/1471-2458-14-1316,PMC4326503,25532562,CC BY,"BACKGROUND: This study investigated the nature of newspaper reporting about online health information in the UK and US. Internet users frequently search for health information online, although the accuracy of the information retrieved varies greatly and can be misleading. Newspapers have the potential to influence public health behaviours, but information has been lacking in relation to how newspapers portray online health information to their readers. METHODS: The newspaper database Nexis(®)UK was searched for articles published from 2003 – 2012 relating to online health information. Systematic content analysis of articles published in the highest circulation newspapers in the UK and US was performed. A second researcher coded a 10% sample to establish inter-rater reliability of coding. RESULTS: In total, 161 newspaper articles were included in the analysis. Publication was most frequent in 2003, 2008 and 2009, which coincided with global threats to public health. UK broadsheet newspapers were significantly more likely to cover online health information than UK tabloid newspapers (p = 0.04) and only one article was identified in US tabloid newspapers. Articles most frequently appeared in health sections. Among the 79 articles that linked online health information to specific diseases or health topics, diabetes was the most frequently mentioned disease, cancer the commonest group of diseases and sexual health the most frequent health topic. Articles portrayed benefits of obtaining online health information more frequently than risks. Quotations from health professionals portrayed mixed opinions regarding public access to online health information. 108 (67.1%) articles directed readers to specific health-related web sites. 135 (83.9%) articles were rated as having balanced judgement and 76 (47.2%) were judged as having excellent quality reporting. No difference was found in the quality of reporting between UK and US articles. CONCLUSIONS: Newspaper coverage of online health information was low during the 10-year period 2003 to 2012. Journalists tended to emphasise the benefits and understate the risks of online health information and the quality of reporting varied considerably. Newspapers directed readers to sources of online health information during global epidemics although, as most articles appeared in the health sections of broadsheet newspapers, coverage was limited to a relatively small readership. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2458-14-1316) contains supplementary material, which is available to authorized users.",2014 Dec 23,"['McCaw, Brian A', 'McGlade, Kieran J', 'McElnay, James C']",BMC Public Health,,,False
e3c13df830390513f48908347eb132df3f2a773e,PMC,Online health information – what the newspapers tell their readers: a systematic content analysis,http://dx.doi.org/10.1186/1471-2458-14-1316,PMC4326503,25532562,CC BY,"BACKGROUND: This study investigated the nature of newspaper reporting about online health information in the UK and US. Internet users frequently search for health information online, although the accuracy of the information retrieved varies greatly and can be misleading. Newspapers have the potential to influence public health behaviours, but information has been lacking in relation to how newspapers portray online health information to their readers. METHODS: The newspaper database Nexis(®)UK was searched for articles published from 2003 – 2012 relating to online health information. Systematic content analysis of articles published in the highest circulation newspapers in the UK and US was performed. A second researcher coded a 10% sample to establish inter-rater reliability of coding. RESULTS: In total, 161 newspaper articles were included in the analysis. Publication was most frequent in 2003, 2008 and 2009, which coincided with global threats to public health. UK broadsheet newspapers were significantly more likely to cover online health information than UK tabloid newspapers (p = 0.04) and only one article was identified in US tabloid newspapers. Articles most frequently appeared in health sections. Among the 79 articles that linked online health information to specific diseases or health topics, diabetes was the most frequently mentioned disease, cancer the commonest group of diseases and sexual health the most frequent health topic. Articles portrayed benefits of obtaining online health information more frequently than risks. Quotations from health professionals portrayed mixed opinions regarding public access to online health information. 108 (67.1%) articles directed readers to specific health-related web sites. 135 (83.9%) articles were rated as having balanced judgement and 76 (47.2%) were judged as having excellent quality reporting. No difference was found in the quality of reporting between UK and US articles. CONCLUSIONS: Newspaper coverage of online health information was low during the 10-year period 2003 to 2012. Journalists tended to emphasise the benefits and understate the risks of online health information and the quality of reporting varied considerably. Newspapers directed readers to sources of online health information during global epidemics although, as most articles appeared in the health sections of broadsheet newspapers, coverage was limited to a relatively small readership. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2458-14-1316) contains supplementary material, which is available to authorized users.",2014 Dec 23,"['McCaw, Brian A', 'McGlade, Kieran J', 'McElnay, James C']",BMC Public Health,,,True
3f94161603e0a339aa90475fe4c7001bb54d1ba7,PMC,Assessment of research productivity of Arab countries in the field of infectious diseases using Web of Science database,http://dx.doi.org/10.1186/2049-9957-4-2,PMC4327970,25685346,CC BY,"BACKGROUND: To meet the future challenges of infectious diseases and limit the spread of multidrug resistant microorganisms, a better understanding of published studies in the field of infectious diseases is needed. The objective of this study was to analyze the quantity and quality of research activity in the field of infectious diseases in Arab countries and compare it with that in non-Arab countries. METHODS: Documents published in Arab countries within the research category of “infectious diseases” were extracted and analyzed using the Web of Science database. The data analyzed represent research productivity during the time interval between 1900 – 2012. RESULTS: Worldwide, the total number of documents published in the field of infectious diseases up to 2012 was 227,188. A total of 2,408 documents in the field of infectious diseases were published in Arab countries, which represents 1.06% of worldwide research output. Research output from Arab countries in the field of infectious diseases was low for decades. However, approximately a five-fold increase was observed in the past decade. Arab countries ranked 56(th) to 218(th) on the standard competition ranking (SCR) in worldwide publications in the field of infectious diseases. Egypt, with a total publication of 464 (19.27%) documents ranked first among Arab countries, while Kuwait University was the most productive institution with a total of 158 (6.56%) documents. Average citation per document published in Arab countries was 13.25 and the h-index was 64. Tuberculosis (230; 9.55%), malaria (223; 9.26%), and hepatitis (189; 7.8%) were the top three infectious diseases studied as according to the retrieved documents. CONCLUSION: The present data reveals that some Arab countries contribute significantly to the field of infectious diseases. However, Arab countries need to work harder to bridge the gap in this field. Compared with non-Arab countries in the Middle East, research output from Arab countries was high, but more efforts are needed to enhance the quality of this output. Future research in the field should be encouraged and correctly directed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-4-2) contains supplementary material, which is available to authorized users.",2015 Feb 2,"['Sweileh, Waleed M', 'Al-Jabi, Samah W', 'Abuzanat, Alaeddin', 'Sawalha, Ansam F', 'AbuTaha, Adham S', 'Ghanim, Mustafa A', 'Zyoud, Sa’ed H']",Infect Dis Poverty,,,False
59acd41ff6a97e730a76fd661b5e10d8cf5290b6,PMC,Assessment of research productivity of Arab countries in the field of infectious diseases using Web of Science database,http://dx.doi.org/10.1186/2049-9957-4-2,PMC4327970,25685346,CC BY,"BACKGROUND: To meet the future challenges of infectious diseases and limit the spread of multidrug resistant microorganisms, a better understanding of published studies in the field of infectious diseases is needed. The objective of this study was to analyze the quantity and quality of research activity in the field of infectious diseases in Arab countries and compare it with that in non-Arab countries. METHODS: Documents published in Arab countries within the research category of “infectious diseases” were extracted and analyzed using the Web of Science database. The data analyzed represent research productivity during the time interval between 1900 – 2012. RESULTS: Worldwide, the total number of documents published in the field of infectious diseases up to 2012 was 227,188. A total of 2,408 documents in the field of infectious diseases were published in Arab countries, which represents 1.06% of worldwide research output. Research output from Arab countries in the field of infectious diseases was low for decades. However, approximately a five-fold increase was observed in the past decade. Arab countries ranked 56(th) to 218(th) on the standard competition ranking (SCR) in worldwide publications in the field of infectious diseases. Egypt, with a total publication of 464 (19.27%) documents ranked first among Arab countries, while Kuwait University was the most productive institution with a total of 158 (6.56%) documents. Average citation per document published in Arab countries was 13.25 and the h-index was 64. Tuberculosis (230; 9.55%), malaria (223; 9.26%), and hepatitis (189; 7.8%) were the top three infectious diseases studied as according to the retrieved documents. CONCLUSION: The present data reveals that some Arab countries contribute significantly to the field of infectious diseases. However, Arab countries need to work harder to bridge the gap in this field. Compared with non-Arab countries in the Middle East, research output from Arab countries was high, but more efforts are needed to enhance the quality of this output. Future research in the field should be encouraged and correctly directed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-4-2) contains supplementary material, which is available to authorized users.",2015 Feb 2,"['Sweileh, Waleed M', 'Al-Jabi, Samah W', 'Abuzanat, Alaeddin', 'Sawalha, Ansam F', 'AbuTaha, Adham S', 'Ghanim, Mustafa A', 'Zyoud, Sa’ed H']",Infect Dis Poverty,,,True
ce8a4f668a135bcd1ff510cef680e548585cef06,PMC,A Serpin Shapes the Extracellular Environment to Prevent Influenza A Virus Maturation,http://dx.doi.org/10.1016/j.cell.2015.01.040,PMC4328142,25679759,CC BY,"Interferon-stimulated genes (ISGs) act in concert to provide a tight barrier against viruses. Recent studies have shed light on the contribution of individual ISG effectors to the antiviral state, but most have examined those acting on early, intracellular stages of the viral life cycle. Here, we applied an image-based screen to identify ISGs inhibiting late stages of influenza A virus (IAV) infection. We unraveled a directly antiviral function for the gene SERPINE1, encoding plasminogen activator inhibitor 1 (PAI-1). By targeting extracellular airway proteases, PAI-1 inhibits IAV glycoprotein cleavage, thereby reducing infectivity of progeny viruses. This was biologically relevant for IAV restriction in vivo. Further, partial PAI-1 deficiency, attributable to a polymorphism in human SERPINE1, conferred increased susceptibility to IAV in vitro. Together, our findings reveal that manipulating the extracellular environment to inhibit the last step in a virus life cycle is an important mechanism of the antiviral response.",2015 Feb 12,"['Dittmann, Meike', 'Hoffmann, Hans-Heinrich', 'Scull, Margaret\xa0A.', 'Gilmore, Rachel\xa0H.', 'Bell, Kierstin\xa0L.', 'Ciancanelli, Michael', 'Wilson, Sam\xa0J.', 'Crotta, Stefania', 'Yu, Yingpu', 'Flatley, Brenna', 'Xiao, Jing\xa0W.', 'Casanova, Jean-Laurent', 'Wack, Andreas', 'Bieniasz, Paul\xa0D.', 'Rice, Charles\xa0M.']",Cell,,,False
fa6fcf0b68fde25abe84c93a517d9965d43c9fbe,PMC,A Serpin Shapes the Extracellular Environment to Prevent Influenza A Virus Maturation,http://dx.doi.org/10.1016/j.cell.2015.01.040,PMC4328142,25679759,CC BY,"Interferon-stimulated genes (ISGs) act in concert to provide a tight barrier against viruses. Recent studies have shed light on the contribution of individual ISG effectors to the antiviral state, but most have examined those acting on early, intracellular stages of the viral life cycle. Here, we applied an image-based screen to identify ISGs inhibiting late stages of influenza A virus (IAV) infection. We unraveled a directly antiviral function for the gene SERPINE1, encoding plasminogen activator inhibitor 1 (PAI-1). By targeting extracellular airway proteases, PAI-1 inhibits IAV glycoprotein cleavage, thereby reducing infectivity of progeny viruses. This was biologically relevant for IAV restriction in vivo. Further, partial PAI-1 deficiency, attributable to a polymorphism in human SERPINE1, conferred increased susceptibility to IAV in vitro. Together, our findings reveal that manipulating the extracellular environment to inhibit the last step in a virus life cycle is an important mechanism of the antiviral response.",2015 Feb 12,"['Dittmann, Meike', 'Hoffmann, Hans-Heinrich', 'Scull, Margaret\xa0A.', 'Gilmore, Rachel\xa0H.', 'Bell, Kierstin\xa0L.', 'Ciancanelli, Michael', 'Wilson, Sam\xa0J.', 'Crotta, Stefania', 'Yu, Yingpu', 'Flatley, Brenna', 'Xiao, Jing\xa0W.', 'Casanova, Jean-Laurent', 'Wack, Andreas', 'Bieniasz, Paul\xa0D.', 'Rice, Charles\xa0M.']",Cell,,,False
164f04163f53a4fb15d74a03b6ab473b50c30989,PMC,Macrophages at the Fork in the Road to Health or Disease,http://dx.doi.org/10.3389/fimmu.2015.00059,PMC4329822,25762997,CC BY,,2015 Feb 16,"['Mills, Charles D.', 'Lenz, Laurel L.', 'Ley, Klaus']",Front Immunol,,,True
6973170d4c8d9576b0e3bfd8391e907d779ee355,PMC,RPI-Pred: predicting ncRNA-protein interaction using sequence and structural information,http://dx.doi.org/10.1093/nar/gkv020,PMC4330382,25609700,CC BY,"RNA-protein complexes are essential in mediating important fundamental cellular processes, such as transport and localization. In particular, ncRNA-protein interactions play an important role in post-transcriptional gene regulation like mRNA localization, mRNA stabilization, poly-adenylation, splicing and translation. The experimental methods to solve RNA-protein interaction prediction problem remain expensive and time-consuming. Here, we present the RPI-Pred (RNA-protein interaction predictor), a new support-vector machine-based method, to predict protein-RNA interaction pairs, based on both the sequences and structures. The results show that RPI-Pred can correctly predict RNA-protein interaction pairs with ∼94% prediction accuracy when using sequence and experimentally determined protein and RNA structures, and with ∼83% when using sequences and predicted protein and RNA structures. Further, our proposed method RPI-Pred was superior to other existing ones by predicting more experimentally validated ncRNA-protein interaction pairs from different organisms. Motivated by the improved performance of RPI-Pred, we further applied our method for reliable construction of ncRNA-protein interaction networks. The RPI-Pred is publicly available at: http://ctsb.is.wfubmc.edu/projects/rpi-pred.",2015 Feb 18,"['Suresh, V.', 'Liu, Liang', 'Adjeroh, Donald', 'Zhou, Xiaobo']",Nucleic Acids Res,,,True
9984fe671d61d99ab39e8e95787e9000093ea7df,PMC,Directed Evolution of a Yeast-Displayed HIV-1 SOSIP gp140 Spike Protein toward Improved Expression and Affinity for Conformational Antibodies,http://dx.doi.org/10.1371/journal.pone.0117227,PMC4331506,25688555,CC BY,"Design of an envelope-based immunogen capable of inducing a broadly neutralizing antibody response is thought to be key to the development of a protective HIV-1 vaccine. However, the broad diversity of viral variants and a limited ability to produce native envelope have hampered such design efforts. Here we describe adaptation of the yeast display system and use of a combinatorial protein engineering approach to permit directed evolution of HIV envelope variants. Because the intrinsic instability and complexity of this trimeric glycoprotein has greatly impeded the development of immunogens that properly represent the structure of native envelope, this platform addresses an essential need for methodologies with the capacity to rapidly engineer HIV spike proteins towards improved homogeneity, stability, and presentation of neutralizing epitopes. We report for the first time the display of a designed SOSIP gp140 on yeast, and the in vitro evolution of derivatives with greatly improved expression and binding to conformation-dependent antibodies. These efforts represent an initial and critical step toward the ability to rapidly engineer HIV-1 envelope immunogens via directed evolution.",2015 Feb 17,"['Grimm, Sebastian K.', 'Battles, Michael B.', 'Ackerman, Margaret E.']",PLoS One,,,True
7e5b5d16ffb537a8e940502af3011d18fe6eff9b,PMC,Genomic Characterization of Novel Circular ssDNA Viruses from Insectivorous Bats in Southern Brazil,http://dx.doi.org/10.1371/journal.pone.0118070,PMC4331541,25688970,CC BY,"Circoviruses are highly prevalent porcine and avian pathogens. In recent years, novel circular ssDNA genomes have recently been detected in a variety of fecal and environmental samples using deep sequencing approaches. In this study the identification of genomes of novel circoviruses and cycloviruses in feces of insectivorous bats is reported. Pan-reactive primers were used targeting the conserved rep region of circoviruses and cycloviruses to screen DNA bat fecal samples. Using this approach, partial rep sequences were detected which formed five phylogenetic groups distributed among the Circovirus and the recently proposed Cyclovirus genera of the Circoviridae. Further analysis using inverse PCR and Sanger sequencing led to the characterization of four new putative members of the family Circoviridae with genome size ranging from 1,608 to 1,790 nt, two inversely arranged ORFs, and canonical nonamer sequences atop a stem loop.",2015 Feb 17,"['Lima, Francisco Esmaile de Sales', 'Cibulski, Samuel Paulo', 'dos Santos, Helton Fernandes', 'Teixeira, Thais Fumaco', 'Varela, Ana Paula Muterle', 'Roehe, Paulo Michel', 'Delwart, Eric', 'Franco, Ana Cláudia']",PLoS One,,,True
8d7f75c01044b85f877a0d1800507cad01edd76b,PMC,Contrasting clinical outcomes in two cohorts of cats naturally infected with feline immunodeficiency virus (FIV),http://dx.doi.org/10.1016/j.vetmic.2014.12.023,PMC4332694,25595267,CC BY,"Despite over 25 years of feline immunodeficiency virus (FIV) research, relatively little is known about the longitudinal course of FIV infection following natural infection. In contrast to published reports of experimental infections using lethal strains of the virus, clinical signs of naturally acquired FIV infection can be mild or inapparent, rather than life-threatening. In this prospective, longitudinal controlled study, based in Chicago, IL (n = 17) and Memphis, TN (n = 27), we investigated two cohorts of privately owned, naturally infected cats kept under different housing conditions. Cats in the Chicago cohort (Group 1) were kept in households of ≤2 cats, while the Memphis cohort (Group 2) comprised part of a large multi-cat household of over 60 cats kept indoors only, with unrestricted access to one another. The majority of cats from Group 1 did not display clinical signs consistent with immunodeficiency during the 22-month observation period. In contrast, the outcome of infection in Group 2 was dramatically different; 17/27 (63%) of cats lost a median of 51.3% of their bodyweight (P < 0.0005) and died during the study period, with lymphoma being the most common cause of mortality. Although the decrease in CD4+ T cell count between enrolment and terminal disease was significant (P = 0.0017), the CD4:CD8 ratio at the time of enrolment did not reliably distinguish FIV-positive cats classified as ‘healthy’ and ‘not healthy’ at either cohort. FIV load at enrolment was significantly lower in Group 1 than in Group 2 (P < 0.0001), but there were no significant differences at enrolment between healthy and not healthy cats at either group. In conclusion, the results of this study suggest that management and housing conditions impact on disease progression and survival times of FIV-positive cats.",2015 Mar 23,"['Bęczkowski, Paweł M.', 'Litster, Annette', 'Lin, Tsang Long', 'Mellor, Dominic J.', 'Willett, Brian J.', 'Hosie, Margaret J.']",Vet Microbiol,,,False
72e37ddb3310bf50385723819244148ab9a787f2,PMC,Comparison of risk factors for seropositivity to feline immunodeficiency virus and feline leukemia virus among cats: a case-case study,http://dx.doi.org/10.1186/s12917-015-0339-3,PMC4332748,25889006,CC BY,"BACKGROUND: Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are reported to have similar risk factors and similar recommendations apply to manage infected cats. However, some contrasting evidence exists in the literature with regard to commonly reported risk factors. In this study, we investigated whether the known risk factors for FIV and FeLV infections have a stronger effect for either infection. This retrospective study included samples from 696 cats seropositive for FIV and 593 cats seropositive for FeLV from the United States and Canada. Data were collected during two cross sectional studies, where cats were tested using IDEXX FIV/FeLV ELISA kits. To compare the effect of known risk factors for FIV infection compared to FeLV, using a case-case study design, random intercept logistic regression models were fit including cats’ age, sex, neuter status, outdoor exposure, health status and type of testing facility as independent variables. A random intercept for testing facility was included to account for clustering expected in testing practices at the individual clinics and shelters. RESULTS: In the multivariable random intercept model, the odds of FIV compared to FeLV positive ELISA results were greater for adults (OR = 2.09, CI: 1.50-2.92), intact males (OR = 3.14, CI: 1.85-3.76), neutered males (OR = 2.68, CI: 1.44- 3.14), cats with outdoor access (OR = 2.58, CI: 1.85-3.76) and lower for cats with clinical illness (OR = 0.60, 95% CI: 0.52-0.90). The variance components obtained from the model indicated clustering at the testing facility level. CONCLUSIONS: Risk factors that have a greater effect on FIV seropositivity include adulthood, being male (neutered or not) and having access to outdoors, while clinical illness was a stronger predictor for FeLV seropositivity. Further studies are warranted to assess the implications of these results for the management and control of these infections.",2015 Feb 10,"['Chhetri, Bimal K', 'Berke, Olaf', 'Pearl, David L', 'Bienzle, Dorothee']",BMC Vet Res,,,True
29c1e7a4bdac021691a22a788312618e8091dd1d,PMC,Acquired immunity and asymptomatic reservoir impact on frontline and airport ebola outbreak syndromic surveillance and response,http://dx.doi.org/10.1186/2049-9957-3-41,PMC4333876,25699182,CC BY,"The number of surveillance networks for infectious disease diagnosis and response has been growing. In 2000, the World Health Organization (WHO) established the Global Outbreak Alert and Response Network, which has been endorsed by each of the 46 WHO African members since then. Yet, taming the dynamics and plague of the vicious Ebola virus disease (EVD) in African countries has been patchy and erratic due to inadequate surveillance and contact tracing, community defiance and resistance, a lack of detection and response systems, meager/weak knowledge and information on the disease, inadequacies in protective materials protocols, contact tracing nightmare and differing priorities at various levels of the public health system. Despite the widespread acceptance of syndromic surveillance (SS) systems, their ability to provide early warning alerts and notifications of outbreaks is still unverified. Information is often too limited for any outbreak, or emerging or otherwise unexpected disease, to be recognized at either the community or the national level. Indeed, little is known about the role and the interactions between the Ebola infection and exposure to other syndemics and the development of acquired immunity, asymptomatic reservoir, and Ebola seroconversion. Can lessons be learnt from smallpox, polio, and influenza immunity, and can immunization against these serve as a guide? In most endemic countries, community health centers and disease control and prevention at airports solely relies on passive routine immunization control and reactive syndromic response. The frontline and airport Ebola SS systems in West Africa have shown deficiencies in terms of responding with an alarming number of case fatalities, and suggest that more detailed insights into Ebola, and proactive actions, are needed. The quest for effective early indicators (EEE) in shifting the public and global health paradigm requires the development and implementation of a comprehensive and effective community or regional integrated pandemic preparedness and surveillance response systems tailored to local contexts. These systems must have mechanisms for early identification, rapid contact tracing and tracking, confirmation, and communication with the local population and the global community, and must endeavor to respond in a timely manner. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-3-41) contains supplementary material, which is available to authorized users.",2014 Oct 29,"['Tambo, Ernest', 'Xiao-Nong, Zhou']",Infect Dis Poverty,,,False
1378320afa873bdb81e3f3314a430c7a208d2d08,PMC,Acquired immunity and asymptomatic reservoir impact on frontline and airport ebola outbreak syndromic surveillance and response,http://dx.doi.org/10.1186/2049-9957-3-41,PMC4333876,25699182,CC BY,"The number of surveillance networks for infectious disease diagnosis and response has been growing. In 2000, the World Health Organization (WHO) established the Global Outbreak Alert and Response Network, which has been endorsed by each of the 46 WHO African members since then. Yet, taming the dynamics and plague of the vicious Ebola virus disease (EVD) in African countries has been patchy and erratic due to inadequate surveillance and contact tracing, community defiance and resistance, a lack of detection and response systems, meager/weak knowledge and information on the disease, inadequacies in protective materials protocols, contact tracing nightmare and differing priorities at various levels of the public health system. Despite the widespread acceptance of syndromic surveillance (SS) systems, their ability to provide early warning alerts and notifications of outbreaks is still unverified. Information is often too limited for any outbreak, or emerging or otherwise unexpected disease, to be recognized at either the community or the national level. Indeed, little is known about the role and the interactions between the Ebola infection and exposure to other syndemics and the development of acquired immunity, asymptomatic reservoir, and Ebola seroconversion. Can lessons be learnt from smallpox, polio, and influenza immunity, and can immunization against these serve as a guide? In most endemic countries, community health centers and disease control and prevention at airports solely relies on passive routine immunization control and reactive syndromic response. The frontline and airport Ebola SS systems in West Africa have shown deficiencies in terms of responding with an alarming number of case fatalities, and suggest that more detailed insights into Ebola, and proactive actions, are needed. The quest for effective early indicators (EEE) in shifting the public and global health paradigm requires the development and implementation of a comprehensive and effective community or regional integrated pandemic preparedness and surveillance response systems tailored to local contexts. These systems must have mechanisms for early identification, rapid contact tracing and tracking, confirmation, and communication with the local population and the global community, and must endeavor to respond in a timely manner. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-3-41) contains supplementary material, which is available to authorized users.",2014 Oct 29,"['Tambo, Ernest', 'Xiao-Nong, Zhou']",Infect Dis Poverty,,,True
997f6355fdf8531d31a8bdadd1067f651e2e3d41,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,True
2ebcfe4ce704a545ee3413d526ca0dbfcbd4e0c1,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
7928df13b8fca67fa1de57294cf18ef7ba6fe4e6,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
5e89b0b0edee59ca1455bcec5397470c0782d906,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
7c449ae509e41ecb0d136c30c81522b4331607bc,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
68fb002c1c445d7d6cd0e6c3318ad0d8147c368c,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
97b4c041c80487b86be2c05a2f1cf3c091476aae,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
a5a2639f5ac0a7f972c19a98303418ce6dedeac2,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
dc5b3e87025a1901e5b0691d164ed524544826f8,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
41f4079c64087ea5c19f504cedb17772034bdca4,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
8f4f337cb823896c59091ccefae014e578799656,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
5a446698400926d20afa361f5c96c11495c90cda,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
144707121f348bf956c21693c153a50700222cc9,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
d31e34a1b5d8447f077c8edd36938c68470db017,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
2aa9d8f84bab8eec05bac2a5bb2295ce3b2f9c77,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
fee84e710586ab2a71c3933594cfb6fdba825e43,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
188ba8443bebdeaecfda34138ac1afa4736351ba,PMC,Correction: Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner,http://dx.doi.org/10.1371/journal.ppat.1004709,PMC4334521,25679792,CC BY,,2015 Feb 13,,PLoS Pathog,,,False
c6e4261e1a6aa596741c8af357661827bff2c468,PMC,Correction: Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner,http://dx.doi.org/10.1371/journal.ppat.1004709,PMC4334521,25679792,CC BY,,2015 Feb 13,,PLoS Pathog,,,True
3339f4bb346bfa3070ae5fc7dc745ef051535b0e,PMC,Correction: Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner,http://dx.doi.org/10.1371/journal.ppat.1004709,PMC4334521,25679792,CC BY,,2015 Feb 13,,PLoS Pathog,,,True
7e55726d345571690d0e3046664cfac5003c2a89,PMC,Investigating the introduction of porcine epidemic diarrhea virus into an Ohio swine operation,http://dx.doi.org/10.1186/s12917-015-0348-2,PMC4334577,25881144,CC BY,"BACKGROUND: Porcine Epidemic Diarrhea virus (PEDV) is a highly transmissible coronavirus that causes a severe enteric disease that is particularly deadly for neonatal piglets. Since its introduction to the United States in 2013, PEDV has spread quickly across the country and has caused significant financial losses to pork producers. With no fully licensed vaccines currently available in the United States, prevention and control of PEDV disease is heavily reliant on biosecurity measures. Despite proven, effective biosecurity practices, multiple sites and production stages, within and across designated production flows in an Ohio swine operation broke with confirmed PEDV in January 2014, leading the producer and attending veterinarian to investigate the route of introduction. CASE PRESENTATION: On January 12, 2014, several sows within a production flow were noted with signs of enteric illness. Within a few days, illness had spread to most of the sows in the facility and was confirmed by RT-PCR to be PEDV. Within a short time period, confirmed disease was present on multiple sites within and across breeding and post weaning production flows of the operation and mortality approached 100% in neonatal piglets. After an epidemiologic investigation, an outsourced, pelleted piglet diet was identified for assessment, and a bioassay, where naïve piglets were fed the suspected feed pellets, was initiated to test the pellets for infectious PEDV. CONCLUSIONS: The epidemiological investigation provided strong evidence for contaminated feed as the source of the outbreak. In addition, feed pellets collected from unopened bags at the affected sites tested positive for PEDV using RT-PCR. However, the bioassay study was not able to show infectivity when feeding the suspected feed pellets to a small number of naïve piglets. The results highlight the critical need for surveillance of feed and feed components to further define transmission avenues in an effort to limit the spread of PEDV throughout the U.S. swine industry.",2015 Feb 15,"['Bowman, Andrew S', 'Krogwold, Roger A', 'Price, Todd', 'Davis, Matt', 'Moeller, Steven J']",BMC Vet Res,,,True
5f83e9b8450e30448ab3c65807f414013a12d179,PMC,Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus,http://dx.doi.org/10.1186/2049-9957-3-43,PMC4334593,25699183,CC BY,"The recent outbreak of the human Zaire ebolavirus (EBOV) epidemic is spiraling out of control in West Africa. Human EBOV hemorrhagic fever has a case fatality rate of up to 90%. The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention, with no approved therapies and vaccines available for its treatment apart from supportive care. Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial, the current epidemic might be outpacing the speed at which drugs and vaccines can be produced. Like all viruses, the EBOV largely relies on host cell factors and physiological processes for its entry, replication, and egress. We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies. Most of the therapeutic agents in this review are directed against non-mutable targets of the host, which is independent of viral mutation. These medications are approved by the Food and Drug Administration (FDA) for the treatment of other diseases. They are available and stockpileable for immediate use. They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-3-43) contains supplementary material, which is available to authorized users.",2014 Nov 28,"['Lai, Kang Yiu', 'Ng, Wing Yiu George', 'Cheng, Fan Fanny']",Infect Dis Poverty,,,False
06190bfcbc53a5d5d17e0a60a3a0f6488d8ae1db,PMC,Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus,http://dx.doi.org/10.1186/2049-9957-3-43,PMC4334593,25699183,CC BY,"The recent outbreak of the human Zaire ebolavirus (EBOV) epidemic is spiraling out of control in West Africa. Human EBOV hemorrhagic fever has a case fatality rate of up to 90%. The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention, with no approved therapies and vaccines available for its treatment apart from supportive care. Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial, the current epidemic might be outpacing the speed at which drugs and vaccines can be produced. Like all viruses, the EBOV largely relies on host cell factors and physiological processes for its entry, replication, and egress. We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies. Most of the therapeutic agents in this review are directed against non-mutable targets of the host, which is independent of viral mutation. These medications are approved by the Food and Drug Administration (FDA) for the treatment of other diseases. They are available and stockpileable for immediate use. They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-3-43) contains supplementary material, which is available to authorized users.",2014 Nov 28,"['Lai, Kang Yiu', 'Ng, Wing Yiu George', 'Cheng, Fan Fanny']",Infect Dis Poverty,,,True
a4cfc3e2cc8c3a69d8a6384aa77b9a9ff7a51dd7,PMC,Role of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation,http://dx.doi.org/10.1371/journal.ppat.1004649,PMC4335073,25695775,CC BY,"The rising prevalence of arthritogenic alphavirus infections, including chikungunya virus (CHIKV) and Ross River virus (RRV), and the lack of antiviral treatments highlight the potential threat of a global alphavirus pandemic. The immune responses underlying alphavirus virulence remain enigmatic. We found that pentraxin 3 (PTX3) was highly expressed in CHIKV and RRV patients during acute disease. Overt expression of PTX3 in CHIKV patients was associated with increased viral load and disease severity. PTX3-deficient (PTX3(-/-)) mice acutely infected with RRV exhibited delayed disease progression and rapid recovery through diminished inflammatory responses and viral replication. Furthermore, binding of the N-terminal domain of PTX3 to RRV facilitated viral entry and replication. Thus, our study demonstrates the pivotal role of PTX3 in shaping alphavirus-triggered immunity and disease and provides new insights into alphavirus pathogenesis.",2015 Feb 19,"['Foo, Suan-Sin', 'Chen, Weiqiang', 'Taylor, Adam', 'Sheng, Kuo-Ching', 'Yu, Xing', 'Teng, Terk-Shin', 'Reading, Patrick C.', 'Blanchard, Helen', 'Garlanda, Cecilia', 'Mantovani, Alberto', 'Ng, Lisa F. P.', 'Herrero, Lara J.', 'Mahalingam, Suresh']",PLoS Pathog,,,True
1e1f8ec1fffc3e243c9c5b53baf146f0e7c6ddb0,PMC,Murine Norovirus 1 (MNV1) Replication Induces Translational Control of the Host by Regulating eIF4E Activity during Infection,http://dx.doi.org/10.1074/jbc.M114.602649,PMC4335213,25561727,CC BY,"Protein synthesis is a tightly controlled process responding to several stimuli, including viral infection. As obligate intracellular parasites, viruses depend on the translation machinery of the host and can manipulate it by affecting the availability and function of specific eukaryotic initiation factors (eIFs). Human norovirus is a member of the Caliciviridae family and is responsible for gastroenteritis outbreaks. Previous studies on feline calicivirus and murine norovirus 1 (MNV1) demonstrated that the viral protein, genome-linked (VPg), acts to direct translation by hijacking the host protein synthesis machinery. Here we report that MNV1 infection modulates the MAPK pathway to activate eIF4E phosphorylation. Our results show that the activation of p38 and Mnk during MNV1 infection is important for MNV1 replication. Furthermore, phosphorylated eIF4E relocates to the polysomes, and this contributes to changes in the translational state of specific host mRNAs. We propose that global translational control of the host by eIF4E phosphorylation is a key component of the host-pathogen interaction.",2015 Feb 20,"['Royall, Elizabeth', 'Doyle, Nicole', 'Abdul-Wahab, Azimah', 'Emmott, Ed', 'Morley, Simon J.', 'Goodfellow, Ian', 'Roberts, Lisa O.', 'Locker, Nicolas']",J Biol Chem,,,True
433cb6b526e64343c82717d42daab33b2379f252,PMC,Small molecules with antiviral activity against the Ebola virus,http://dx.doi.org/10.12688/f1000research.6120.1,PMC4335594,25713700,CC BY,"The recent outbreak of the Ebola virus in West Africa has highlighted the clear shortage of broad-spectrum antiviral drugs for emerging viruses. There are numerous FDA approved drugs and other small molecules described in the literature that could be further evaluated for their potential as antiviral compounds. These molecules are in addition to the few new antivirals that have been tested in Ebola patients but were not originally developed against the Ebola virus, and may play an important role as we await an effective vaccine. The balance between using FDA approved drugs versus novel antivirals with minimal safety and no efficacy data in humans should be considered. We have evaluated 55 molecules from the perspective of an experienced medicinal chemist as well as using simple molecular properties and have highlighted 16 compounds that have desirable qualities as well as those that may be less desirable. In addition we propose that a collaborative database for sharing such published and novel information on small molecules is needed for the research community studying the Ebola virus.",2015 Feb 9,"['Litterman, Nadia', 'Lipinski, Christopher', 'Ekins, Sean']",F1000Res,,,True
3c8f08f49903aa46c23718a59a6bb221879aa1d2,PMC,The Nucleocapsid Protein of Human Coronavirus NL63,http://dx.doi.org/10.1371/journal.pone.0117833,PMC4336326,25700263,CC0,"Human coronavirus (HCoV) NL63 was first described in 2004 and is associated with respiratory tract disease of varying severity. At the genetic and structural level, HCoV-NL63 is similar to other members of the Coronavirinae subfamily, especially human coronavirus 229E (HCoV-229E). Detailed analysis, however, reveals several unique features of the pathogen. The coronaviral nucleocapsid protein is abundantly present in infected cells. It is a multi-domain, multi-functional protein important for viral replication and a number of cellular processes. The aim of the present study was to characterize the HCoV-NL63 nucleocapsid protein. Biochemical analyses revealed that the protein shares characteristics with homologous proteins encoded in other coronaviral genomes, with the N-terminal domain responsible for nucleic acid binding and the C-terminal domain involved in protein oligomerization. Surprisingly, analysis of the subcellular localization of the N protein of HCoV-NL63 revealed that, differently than homologous proteins from other coronaviral species except for SARS-CoV, it is not present in the nucleus of infected or transfected cells. Furthermore, no significant alteration in cell cycle progression in cells expressing the protein was observed. This is in stark contrast with results obtained for other coronaviruses, except for the SARS-CoV.",2015 Feb 20,"['Zuwała, Kaja', 'Golda, Anna', 'Kabala, Wojciech', 'Burmistrz, Michał', 'Zdzalik, Michal', 'Nowak, Paulina', 'Kedracka-Krok, Sylwia', 'Zarebski, Mirosław', 'Dobrucki, Jerzy', 'Florek, Dominik', 'Zeglen, Sławomir', 'Wojarski, Jacek', 'Potempa, Jan', 'Dubin, Grzegorz', 'Pyrc, Krzysztof']",PLoS One,,,True
0ce0b8bb68417974932e98c094ec93fbefc5193b,PMC,Targeting interferon response genes sensitizes aromatase inhibitor resistant breast cancer cells to estrogen-induced cell death,http://dx.doi.org/10.1186/s13058-014-0506-7,PMC4336497,25588716,CC BY,"INTRODUCTION: Estrogen deprivation using aromatase inhibitors (AIs) is currently the standard of care for postmenopausal women with hormone receptor-positive breast cancer. Unfortunately, the majority of patients treated with AIs eventually develop resistance, inevitably resulting in patient relapse and, ultimately, death. The mechanism by which resistance occurs is still not completely known, however, recent studies suggest that impaired/defective interferon signaling might play a role. In the present study, we assessed the functional role of IFITM1 and PLSCR1; two well-known interferon response genes in AI resistance. METHODS: Real-time PCR and Western blot analyses were used to assess mRNA and protein levels of IFITM1, PLSCR1, STAT1, STAT2, and IRF-7 in AI-resistant MCF-7:5C breast cancer cells and AI-sensitive MCF-7 and T47D cells. Immunohistochemistry (IHC) staining was performed on tissue microarrays consisting of normal breast tissues, primary breast tumors, and AI-resistant recurrence tumors. Enzyme-linked immunosorbent assay was used to quantitate intracellular IFNα level. Neutralizing antibody was used to block type 1 interferon receptor IFNAR1 signaling. Small interference RNA (siRNA) was used to knockdown IFITM1, PLSCR1, STAT1, STAT2, IRF-7, and IFNα expression. RESULTS: We found that IFITM1 and PLSCR1 were constitutively overexpressed in AI-resistant MCF-7:5C breast cancer cells and AI-resistant tumors and that siRNA knockdown of IFITM1 significantly inhibited the ability of the resistant cells to proliferate, migrate, and invade. Interestingly, suppression of IFITM1 significantly enhanced estradiol-induced cell death in AI-resistant MCF-7:5C cells and markedly increased expression of p21, Bax, and Noxa in these cells. Significantly elevated level of IFNα was detected in AI-resistant MCF-7:5C cells compared to parental MCF-7 cells and suppression of IFNα dramatically reduced IFITM1, PLSCR1, p-STAT1, and p-STAT2 expression in the resistant cells. Lastly, neutralizing antibody against IFNAR1/2 and knockdown of STAT1/STAT2 completely suppressed IFITM1, PLSCR1, p-STAT1, and p-STAT2 expression in the resistant cells, thus confirming the involvement of the canonical IFNα signaling pathway in driving the overexpression of IFITM1 and other interferon-stimulated genes (ISGs) in the resistant cells. CONCLUSION: Overall, these results demonstrate that constitutive overexpression of ISGs enhances the progression of AI-resistant breast cancer and that suppression of IFITM1 and other ISGs sensitizes AI-resistant cells to estrogen-induced cell death. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-014-0506-7) contains supplementary material, which is available to authorized users.",2015 Jan 15,"['Choi, Hye Joung', 'Lui, Asona', 'Ogony, Joshua', 'Jan, Rifat', 'Sims, Peter J', 'Lewis-Wambi, Joan']",Breast Cancer Res,,,True
684a0a1db464c0c6e1571a6ca9ea5d2003f62456,PMC,Aberrant expression of long noncoding RNAs in chronic thromboembolic pulmonary hypertension,http://dx.doi.org/10.3892/mmr.2014.3102,PMC4337719,25522749,CC BY,"Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the primary causes of severe pulmonary hypertension. In order to identify long noncoding RNAs (lncRNAs) that may be involved in the development of CTEPH, comprehensive lncRNA and messenger RNA (mRNA) profiling of endothelial tissues from the pulmonary arteries of CTEPH patients was conducted with microarray analysis. Differential expression of 185 lncRNAs was observed in the CTEPH tissues compared with healthy control tissues. Further analysis identified 464 regulated enhancer-like lncRNAs and overlapping, antisense or nearby mRNA pairs. Coexpression networks were subsequently constructed and investigated. The expression levels of the lncRNAs, NR_036693, NR_027783, NR_033766 and NR_001284, were significantly altered. Gene ontology and pathway analysis demonstrated the potential role of lncRNAs in the regulation of central process, including inflammatory response, response to endogenous stimulus and antigen processing and presentation. The use of bioinformatics may help to uncover and analyze large quantities of data identified by microarray analyses, through rigorous experimental planning, statistical analysis and the collection of more comprehensive data regarding CTEPH. The results of the present study provided evidence which may be helpful in future studies on the diagnosis and management of CTEPH.",2015 Apr 17,"['GU, SONG', 'LI, GUANGHUI', 'ZHANG, XITAO', 'YAN, JUN', 'GAO, JIE', 'AN, XIANGGUANG', 'LIU, YAN', 'SU, PIXIONG']",Mol Med Rep,,,True
bb8a9e29bc65471177f470285c32d879c2cb7263,PMC,Effectiveness of traveller screening for emerging pathogens is shaped by epidemiology and natural history of infection,http://dx.doi.org/10.7554/eLife.05564,PMC4337724,25695520,CC BY,"During outbreaks of high-consequence pathogens, airport screening programs have been deployed to curtail geographic spread of infection. The effectiveness of screening depends on several factors, including pathogen natural history and epidemiology, human behavior, and characteristics of the source epidemic. We developed a mathematical model to understand how these factors combine to influence screening outcomes. We analyzed screening programs for six emerging pathogens in the early and late stages of an epidemic. We show that the effectiveness of different screening tools depends strongly on pathogen natural history and epidemiological features, as well as human factors in implementation and compliance. For pathogens with longer incubation periods, exposure risk detection dominates in growing epidemics, while fever becomes a better target in stable or declining epidemics. For pathogens with short incubation, fever screening drives detection in any epidemic stage. However, even in the most optimistic scenario arrival screening will miss the majority of cases. DOI: http://dx.doi.org/10.7554/eLife.05564.001",,"['Gostic, Katelyn M', 'Kucharski, Adam J', 'Lloyd-Smith, James O']",eLife.; 4:e05564,,,True
3118aa53f6b7e539049e2a52e973f4124ba121e9,PMC,First Discovery of Acetone Extract from Cottonseed Oil Sludge as a Novel Antiviral Agent against Plant Viruses,http://dx.doi.org/10.1371/journal.pone.0117496,PMC4337905,25705894,CC BY,"A novel acetone extract from cottonseed oil sludge was firstly discovered against plant viruses including Tobacco mosaic virus (TMV), Rice stripe virus (RSV) and Southern rice black streaked dwarf virus (SRBSDV). Gossypol and β-sitosterol separated from the acetone extract were tested for their effects on anti-TMV and analysed by nuclear magnetic resonance (NMR) assay. In vivo and field trials in different geographic distributions and different host varieties declared that this extract mixture was more efficient than the commercial agent Ningnanmycin with a broad spectrum of anti-plant-viruses activity. No phytotoxic activity was observed in the treated plants and environmental toxicology showed that this new acetone extract was environmentally friendly, indicating that this acetone extract has potential application in the control of plant virus in the future.",2015 Feb 23,"['Zhao, Lei', 'Feng, Chaohong', 'Hou, Caiting', 'Hu, Lingyun', 'Wang, Qiaochun', 'Wu, Yunfeng']",PLoS One,,,True
b4e24eaf67301135a909892450e011eaaa27f780,PMC,Analysis of Cathepsin and Furin Proteolytic Enzymes Involved in Viral Fusion Protein Activation in Cells of the Bat Reservoir Host,http://dx.doi.org/10.1371/journal.pone.0115736,PMC4338073,25706132,CC BY,"Bats of different species play a major role in the emergence and transmission of highly pathogenic viruses including Ebola virus, SARS-like coronavirus and the henipaviruses. These viruses require proteolytic activation of surface envelope glycoproteins needed for entry, and cellular cathepsins have been shown to be involved in proteolysis of glycoproteins from these distinct virus families. Very little is currently known about the available proteases in bats. To determine whether the utilization of cathepsins by bat-borne viruses is related to the nature of proteases in their natural hosts, we examined proteolytic processing of several viral fusion proteins in cells derived from two fruit bat species, Pteropus alecto and Rousettus aegyptiacus. Our work shows that fruit bat cells have homologs of cathepsin and furin proteases capable of cleaving and activating both the cathepsin-dependent Hendra virus F and the furin-dependent parainfluenza virus 5 F proteins. Sequence analysis comparing Pteropus alecto furin and cathepsin L to proteases from other mammalian species showed a high degree of conservation; however significant amino acid variation occurs at the C-terminus of Pteropus alecto furin. Further analysis of furin-like proteases from fruit bats revealed that these proteases are catalytically active and resemble other mammalian furins in their response to a potent furin inhibitor. However, kinetic analysis suggests that differences may exist in the cellular localization of furin between different species. Collectively, these results indicate that the unusual role of cathepsin proteases in the life cycle of bat-borne viruses is not due to the lack of active furin-like proteases in these natural reservoir species; however, differences may exist between furin proteases present in fruit bats compared to furins in other mammalian species, and these differences may impact protease usage for viral glycoprotein processing.",2015 Feb 23,"['El Najjar, Farah', 'Lampe, Levi', 'Baker, Michelle L.', 'Wang, Lin-Fa', 'Dutch, Rebecca Ellis']",PLoS One,,,True
d17a83f05547d542975169b6d43912eae3afd17b,PMC,Structural analysis of herpes simplex virus by optical super-resolution imaging,http://dx.doi.org/10.1038/ncomms6980,PMC4338551,25609143,CC BY,"Herpes simplex virus type-1 (HSV-1) is one of the most widespread pathogens among humans. Although the structure of HSV-1 has been extensively investigated, the precise organization of tegument and envelope proteins remains elusive. Here we use super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) in combination with a model-based analysis of single-molecule localization data, to determine the position of protein layers within virus particles. We resolve different protein layers within individual HSV-1 particles using multi-colour dSTORM imaging and discriminate envelope-anchored glycoproteins from tegument proteins, both in purified virions and in virions present in infected cells. Precise characterization of HSV-1 structure was achieved by particle averaging of purified viruses and model-based analysis of the radial distribution of the tegument proteins VP16, VP1/2 and pUL37, and envelope protein gD. From this data, we propose a model of the protein organization inside the tegument.",2015 Jan 22,"['Laine, Romain F.', 'Albecka, Anna', 'van de Linde, Sebastian', 'Rees, Eric J.', 'Crump, Colin M.', 'Kaminski, Clemens F.']",Nat Commun,,,True
73b5a68dd7e80ad291c026145c875eb8338daa08,PMC,Structural analysis of herpes simplex virus by optical super-resolution imaging,http://dx.doi.org/10.1038/ncomms6980,PMC4338551,25609143,CC BY,"Herpes simplex virus type-1 (HSV-1) is one of the most widespread pathogens among humans. Although the structure of HSV-1 has been extensively investigated, the precise organization of tegument and envelope proteins remains elusive. Here we use super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) in combination with a model-based analysis of single-molecule localization data, to determine the position of protein layers within virus particles. We resolve different protein layers within individual HSV-1 particles using multi-colour dSTORM imaging and discriminate envelope-anchored glycoproteins from tegument proteins, both in purified virions and in virions present in infected cells. Precise characterization of HSV-1 structure was achieved by particle averaging of purified viruses and model-based analysis of the radial distribution of the tegument proteins VP16, VP1/2 and pUL37, and envelope protein gD. From this data, we propose a model of the protein organization inside the tegument.",2015 Jan 22,"['Laine, Romain F.', 'Albecka, Anna', 'van de Linde, Sebastian', 'Rees, Eric J.', 'Crump, Colin M.', 'Kaminski, Clemens F.']",Nat Commun,,,True
c13377750d32446f66a4bcd0bb2da626e4b2a035,PMC,Pilgrims and MERS-CoV: what’s the risk?,http://dx.doi.org/10.1186/s12982-015-0025-8,PMC4339294,25717340,CC BY,"The risk of Middle East Respiratory Syndrome Coronavirus spreading globally is worrying, given the annual mass gathering of the Hajj and the year-long influx of pilgrims undertaking the Umrah. Based on the incidence in Saudi Arabia since June 2012, the most likely scenario given recent pilgrim numbers is estimated to be one case per Hajj, and three Umrah pilgrims per year, but which could plausibly reach seven and ten pilgrims respectively. In addition to the 2015 Hajj, national surveillance systems should be on the alert for the low but long-lasting risk of infected pilgrims returning from the Umrah throughout the year.",2015 Feb 18,"['Soliman, Tarek', 'Cook, Alex R', 'Coker, Richard J']",Emerg Themes Epidemiol,,,True
a4d06a5b2f6f7b1071b36b9ba083e757d0f4ec97,PMC,Humanitarian Access to Unapproved Interventions in Public Health Emergencies of International Concern,http://dx.doi.org/10.1371/journal.pmed.1001793,PMC4339858,25710504,CC BY,Jerome Singh considers how regulatory mechanisms can allow access to experimental interventions in humanitarian emergencies such as the Ebola epidemic.,2015 Feb 24,"Singh, Jerome Amir",PLoS Med,,,True
360a370b63f370b54fa937b5ca0078606acaf805,PMC,Tough challenges for testing Ebola therapeutics,http://dx.doi.org/10.2471/BLT.15.020215,PMC4339970,25883398,CC BY,"Therapies for Ebola virus disease are urgently needed, but they must be rigorously tested for safety and efficacy before any mass roll-out to patients. Fiona Fleck reports.",2015 Feb 1,,Bull World Health Organ,,,False
917928bee48f4118e1f14349d4176df8281e9cac,PMC,Diffuse parenchymal lung disease as first clinical manifestation of GATA-2 deficiency in childhood,http://dx.doi.org/10.1186/s12890-015-0006-2,PMC4340788,25879889,CC BY,"BACKGROUND: GATA-2 transcription factor deficiency has recently been described in patients with a propensity towards myeloid malignancy associated with other highly variable phenotypic features: chronic leukocytopenias (dendritic cell-, monocyto-, granulocyto-, lymphocytopenia), increased susceptibility to infections, lymphatic vasculature abnormalities, and sensorineural deafness. Patients often suffer from opportunistic respiratory infections; chronic pulmonary changes have been found in advanced disease. CASE PRESENTATION: We present a case of a 17-year-old previously healthy Caucasian male who was admitted to the hospital with fever, malaise, headache, cough and dyspnea. A chest X-ray revealed bilateral interstitial infiltrates and pneumonia was diagnosed. Despite prompt clinical improvement under antibiotic therapy, interstitial changes remained stable. A high resolution computer tomography showed severe diffuse parenchymal lung disease, while the patient’s pulmonary function tests were normal and he was asymptomatic. Lung tissue biopsy revealed chronic reparative and resorptive reaction with organizing vasculitis. At the time of the initial presentation to the hospital, serological signs of acute infection with Epstein-Barr virus (EBV) were present; EBV viremia with atypical serological response persisted during two-year follow up. No other infectious agents were found. Marked monocytopenia combined with B-cell lymphopenia led to a suspicion of GATA-2 deficiency. Diagnosis was confirmed by detection of the previously published heterozygous mutation in GATA2 (c.1081 C > T, p.R361C). The patient’s brother and father were both carriers of the same genetic defect. The brother had no clinically relevant ailments despite leukocyte changes similar to the index patient. The father suffered from spondylarthritis, and apart from B-cell lymphopenia, no other changes within the leukocyte pool were seen. CONCLUSION: We conclude that a diagnosis of GATA-2 deficiency should be considered in all patients with diffuse parenchymal lung disease presenting together with leukocytopenia, namely monocyto-, dendritic cell- and B-lymphopenia, irrespective of severity of the clinical phenotype. Genetic counseling and screening for GATA2 mutations within the patient’s family should be provided as the phenotype is highly variable and carriers without apparent immunodeficiency are still in danger of developing myeloid malignancy. A prompt recognition of this rare condition helps to direct clinical treatment strategies and follow-up procedures.",2015 Feb 10,"['Svobodova, Tamara', 'Mejstrikova, Ester', 'Salzer, Ulrich', 'Sukova, Martina', 'Hubacek, Petr', 'Matej, Radoslav', 'Vasakova, Martina', 'Hornofova, Ludmila', 'Dvorakova, Marcela', 'Fronkova, Eva', 'Votava, Felix', 'Freiberger, Tomas', 'Pohunek, Petr', 'Stary, Jan', 'Janda, Ales']",BMC Pulm Med,,,True
7cdb43f29cfdaaa897797a4dfddb41de79b23287,PMC,Emerging and re-emerging infectious diseases: challenges and opportunities for militaries,http://dx.doi.org/10.1186/2054-9369-1-21,PMC4341224,25722877,CC BY,"The communal nature of living and training environments, alongside suboptimal hygiene and stressors in the field, place military personnel at higher risk of contracting emerging infectious diseases. Some of these diseases spread quickly within ranks resulting in large outbreaks, and personnel deployed are also often immunologically naïve to otherwise uncommonly-encountered pathogens. Furthermore, the chance of weaponised biological agents being used in conventional warfare or otherwise remains a very real, albeit often veiled, threat. However, such challenges also provide opportunities for the advancement of preventive and therapeutic military medicine, some of which have been later adopted in civilian settings. Some of these include improved surveillance, new vaccines and drugs, better public health interventions and inter-agency co-operations. The legacy of successes in dealing with infectious diseases is a reminder of the importance in sustaining efforts aimed at ensuring a safer environment for both military and the community at large.",2014 Sep 24,"['Ho, Zheng Jie Marc', 'Hwang, Yi Fu Jeff', 'Lee, Jian Ming Vernon']",Mil Med Res,,,True
9c7ef724d9e2d25e32eceb1ed8a9fe417fe32309,PMC,Effects of Storage Time on Total Protein and Globulin Concentrations in Bovine Fresh Frozen Plasma Obtained for Transfusion,http://dx.doi.org/10.1155/2015/752724,PMC4342078,25767825,CC BY,"To evaluate the effects of storage conditions on total protein (TP) and globulin fractions in fresh frozen bovine plasma units prepared and stored for transfusion, TP and globulin fractions were evaluated in fresh plasma and at 1 month and 6 and 12 months after blood collection in plasma stored at −20°C. Significant differences in concentrations were found in the median concentration of total protein (P = 0.0336), between 0 months and 1 month (P = 0.0108), 0 and 6 months (P = 0.0023), and 0 and 12 months (P = 0.0027), in mean concentration (g/dL) of albumin (P = 0.0394), between 0 months and 1 month (P = 0.0131), 0 and 6 months (P = 0.0035), and 0 and 12 months (P = 0.0038), and beta-2 fraction (P = 0.0401), between 0 and 6 months (P = 0.0401) and 0 and 12 months (P = 0.0230). This study suggests that total gamma globulin concentration in bovine frozen plasma is stable for 12 months at −20°C. Total protein, ALB, and beta-2 fraction have significantly different concentrations (g/dL) when compared to prestorage. This study has shown IgG protein fraction stability in bovine fresh frozen plasma collected for transfusion; therefore, bovine fresh frozen plasma seems to be suitable for the treatment of hypogammaglobulinemia (failure of passive transfer) in calves when stored for 12 months at −20°C.",2015 Feb 12,"['Proverbio, D.', 'Spada, E.', 'Baggiani, L.', 'Bagnagatti De Giorgi, G.', 'Roggero, N.', 'Belloli, A.', 'Pravettoni, D.', 'Perego, R.']",ScientificWorldJournal,,,True
facba90187f6bee3be651d71fc54a715055eaa1d,PMC,Viral etiology of community-acquired pneumonia among adolescents and adults with mild or moderate severity and its relation to age and severity,http://dx.doi.org/10.1186/s12879-015-0808-0,PMC4342096,25812108,CC BY,"BACKGROUND: Better knowledge of distribution of respiratory viruses (RVs) in adolescents and adults with community-acquired pneumonia (CAP) is needed. METHODS: To investigate the RVs etiology among adolescents and adults with CAP, according to age and pneumonia severity index (PSI), a multi-center, prospective study was conducted from November 2010 to April 2012. Fifteen RVs were tested by polymerase chain reaction (PCR). Bacteria were detected by urinary antigen, conventional culture and PCR. RESULTS: Mean (SD) age and median (IQR) PSI score of 954 patients enrolled was 45.2 (19.5) years (range 14–94) and 42 (36). RVs were found in 262 patients (27.5%): influenza virus A (IFV A, 9.9%) comprised of pandemic H1N1 (6.7%) and seasonal H3N2 (3.5%), human rhinovirus (4.3%), adenovirus (4.2%), human metapneumovirus (1.8%), parainfluenza virus 1, 3 and 2 (1.7%, 1.5% and 1.2%). Influenza virus B, enterovirus, respiratory syncytial virus, human coronavirus and parainfluenza virus 4 were rarely detected (<1%). Frequency of IFV A was highest among patients aged between 45–64 years (p < 0.001), while adenovirus among patients aged 14–17 years (p < 0.001), no differences was found in other RVs. The proportion of pandemic H1N1 increased with severity of pneumonia evaluated by PSI (P < 0.05). CONCLUSIONS: The proportion of RVs in CAP is higher than previously reported. IFV A pneumonia are usually found in patients older than 45 years, while, adenovirus pneumonia are common in adolescents and young adults. Pandemic H1N1 virus is still recognized by PSI as a high-severity pathogen. The findings contribute baseline data on viral CAP study in China.",2015 Feb 22,"['Qu, Jiu-Xin', 'Gu, Li', 'Pu, Zeng-Hui', 'Yu, Xiao-Min', 'Liu, Ying-Mei', 'Li, Ran', 'Wang, Yi-Min', 'Cao, Bin', 'Wang, Chen', None]",BMC Infect Dis,,,True
60bb4454a34fb7642d6805ff6261abc91809a135,PMC,"Drainage systems, an occluded source of sanitation related outbreaks",http://dx.doi.org/10.1186/s13690-014-0056-6,PMC4342212,25722855,CC BY,"BACKGROUND: Drainage systems and its role in sanitation related outbreaks are evident but still occluded once it has been installed. This current review evaluates if drainage systems can cause infections and thus be of clinical concern. METHOD: A review of the literature was analyzed. Papers, guidelines, and quality management systems have been considered. RESULTS: Adequate sanitation is fundamental and a prerequisite for safe life and productivity. In contrast, malfunctioning sanitation has been reported to cause outbreaks all over the world. In areas with no sanitation, diarrheal mortality is high and has been shown to decrease by 36% after interventions to improve sanitation. Often, infections are faeces associated and when present in wastewater and sewage sludge poses a high risk of infection upon exposure. Hence, there are working safety guidelines and in industries where infection reduction is essential strict quality assurance systems, i.e. HACCP (hazard analysis critical control points) and GMP (Good Manufacturing Practice) must be complied. Healthcare has recently taken interest in the HACCP system in their efforts to reduce healthcare associated infections as a response to increasing number of ineffective antibiotics and the threat of mortality rate like the pre-antibiotic era. The last few years have called for immediate action to contain the emergence of increasing resistant microorganisms. Resistance is obtained as a result of overuse and misuse of antibiotics in both healthcare and agriculture. Also, by the discharge of antibiotics from manufacturers, healthcare and society. One mechanism of development of novel resistant pathogens has been shown to be by effortless sharing of genetic mobile elements coding for resistance from microbes in the environment to human microbes. These pathogens have been sampled from the drainage systems. These were noticed owing to their possession of an unusual antibiotic resistance profile linking them to the outbreak. Often the cause of sanitation related outbreaks is due to inadequate sanitation and maintenance. However, in general these infections probably go unnoticed. CONCLUSION: Drainage systems and its maintenance, if neglected, could pose a threat in both community and healthcare causing infections as well as emergence of multi-resistant bacteria that could cause unpredictable clinical manifestations.",2015 Feb 26,"Blom, Kristina",Arch Public Health,,,True
473b926e3266337d27883cca29c6186faf3d7ba2,PMC,Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection,http://dx.doi.org/10.1371/journal.pone.0118345,PMC4342244,25719445,CC0,"Ebola virus (EBOV) causes a severe hemorrhagic disease with high fatality. Virus-like particles (VLPs) are a promising vaccine candidate against EBOV. We recently showed that VLPs protect mice from lethal EBOV infection when given before or after viral infection. To elucidate pathways through which VLPs confer post-exposure protection, we investigated the role of type I interferon (IFN) signaling. We found that VLPs lead to accelerated induction of IFN stimulated genes (ISGs) in liver and spleen of wild type mice, but not in Ifnar(-/-) mice. Accordingly, EBOV infected Ifnar(-/-) mice, unlike wild type mice succumbed to death even after VLP treatment. The ISGs induced in wild type mice included anti-viral proteins and negative feedback factors known to restrict viral replication and excessive inflammatory responses. Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar(-/-) mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. Together, this study indicates that VLPs afford post-exposure protection by promoting expeditious initiation of type I IFN signaling in the host.",2015 Feb 26,"['Ayithan, Natarajan', 'Bradfute, Steven B.', 'Anthony, Scott M.', 'Stuthman, Kelly S.', 'Bavari, Sina', 'Bray, Mike', 'Ozato, Keiko']",PLoS One,,,True
efc1b7d8cc09b229c5cd7cda3a8ff8446e0d8b63,PMC,"New Insights into Flavivirus Evolution, Taxonomy and Biogeographic History, Extended by Analysis of Canonical and Alternative Coding Sequences",http://dx.doi.org/10.1371/journal.pone.0117849,PMC4342338,25719412,CC BY,"To generate the most diverse phylogenetic dataset for the flaviviruses to date, we determined the genomic sequences and phylogenetic relationships of 14 flaviviruses, of which 10 are primarily associated with Culex spp. mosquitoes. We analyze these data, in conjunction with a comprehensive collection of flavivirus genomes, to characterize flavivirus evolutionary and biogeographic history in unprecedented detail and breadth. Based on the presumed introduction of yellow fever virus into the Americas via the transatlantic slave trade, we extrapolated a timescale for a relevant subset of flaviviruses whose evolutionary history, shows that different Culex-spp. associated flaviviruses have been introduced from the Old World to the New World on at least five separate occasions, with 2 different sets of factors likely to have contributed to the dispersal of the different viruses. We also discuss the significance of programmed ribosomal frameshifting in a central region of the polyprotein open reading frame in some mosquito-associated flaviviruses.",2015 Feb 26,"['Moureau, Gregory', 'Cook, Shelley', 'Lemey, Philippe', 'Nougairede, Antoine', 'Forrester, Naomi L.', 'Khasnatinov, Maxim', 'Charrel, Remi N.', 'Firth, Andrew E.', 'Gould, Ernest A.', 'de Lamballerie, Xavier']",PLoS One,,,True
f879891cd4353fbb6baa973c04bc1cf2dc3a3fd6,PMC,Field pathogenomics reveals the emergence of a diverse wheat yellow rust population,http://dx.doi.org/10.1186/s13059-015-0590-8,PMC4342793,25723868,CC BY,"BACKGROUND: Emerging and re-emerging pathogens imperil public health and global food security. Responding to these threats requires improved surveillance and diagnostic systems. Despite their potential, genomic tools have not been readily applied to emerging or re-emerging plant pathogens such as the wheat yellow (stripe) rust pathogen Puccinia striiformis f. sp. tritici (PST). This is due largely to the obligate parasitic nature of PST, as culturing PST isolates for DNA extraction remains slow and tedious. RESULTS: To counteract the limitations associated with culturing PST, we developed and applied a field pathogenomics approach by transcriptome sequencing infected wheat leaves collected from the field in 2013. This enabled us to rapidly gain insights into this emerging pathogen population. We found that the PST population across the United Kingdom (UK) underwent a major shift in recent years. Population genetic structure analyses revealed four distinct lineages that correlated to the phenotypic groups determined through traditional pathology-based virulence assays. Furthermore, the genetic diversity between members of a single population cluster for all 2013 PST field samples was much higher than that displayed by historical UK isolates, revealing a more diverse population of PST. CONCLUSIONS: Our field pathogenomics approach uncovered a dramatic shift in the PST population in the UK, likely due to a recent introduction of a diverse set of exotic PST lineages. The methodology described herein accelerates genetic analysis of pathogen populations and circumvents the difficulties associated with obligate plant pathogens. In principle, this strategy can be widely applied to a variety of plant pathogens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0590-8) contains supplementary material, which is available to authorized users.",2015 Feb 25,"['Hubbard, Amelia', 'Lewis, Clare M', 'Yoshida, Kentaro', 'Ramirez-Gonzalez, Ricardo H', 'de Vallavieille-Pope, Claude', 'Thomas, Jane', 'Kamoun, Sophien', 'Bayles, Rosemary', 'Uauy, Cristobal', 'Saunders, Diane GO']",Genome Biol,,,True
1dc4f757f425b080168840089f1f4d29bac75f51,PMC,Identifying Meteorological Drivers for the Seasonal Variations of Influenza Infections in a Subtropical City — Hong Kong,http://dx.doi.org/10.3390/ijerph120201560,PMC4344680,25635916,CC BY,"Compared with temperate areas, the understanding of seasonal variations of influenza infections is lacking in subtropical and tropical regions. Insufficient information about viral activity increases the difficulty of forecasting the disease burden and thus hampers official preparation efforts. Here we identified potential meteorological factors that drove the seasonal variations in influenza infections in a subtropical city, Hong Kong. We fitted the meteorological data and influenza mortality data from 2002 to 2009 in a Susceptible-Infected-Recovered model. From the results, air temperature was a common significant driver of seasonal patterns and cold temperature was associated with an increase in transmission intensity for most of the influenza epidemics. Except 2004, the fitted models with significant meteorological factors could account for more than 10% of the variance in additional to the null model. Rainfall was also found to be a significant driver of seasonal influenza, although results were less robust. The identified meteorological indicators could alert officials to take appropriate control measures for influenza epidemics, such as enhancing vaccination activities before cold seasons. Further studies are required to fully justify the associations.",2015 Feb 28,"['Chong, Ka Chun', 'Goggins, William', 'Zee, Benny Chung Ying', 'Wang, Maggie Haitian']",Int J Environ Res Public Health,,,True
d2b4b984732c78ae39fa9f699232153758583d51,PMC,Identifying Meteorological Drivers for the Seasonal Variations of Influenza Infections in a Subtropical City — Hong Kong,http://dx.doi.org/10.3390/ijerph120201560,PMC4344680,25635916,CC BY,"Compared with temperate areas, the understanding of seasonal variations of influenza infections is lacking in subtropical and tropical regions. Insufficient information about viral activity increases the difficulty of forecasting the disease burden and thus hampers official preparation efforts. Here we identified potential meteorological factors that drove the seasonal variations in influenza infections in a subtropical city, Hong Kong. We fitted the meteorological data and influenza mortality data from 2002 to 2009 in a Susceptible-Infected-Recovered model. From the results, air temperature was a common significant driver of seasonal patterns and cold temperature was associated with an increase in transmission intensity for most of the influenza epidemics. Except 2004, the fitted models with significant meteorological factors could account for more than 10% of the variance in additional to the null model. Rainfall was also found to be a significant driver of seasonal influenza, although results were less robust. The identified meteorological indicators could alert officials to take appropriate control measures for influenza epidemics, such as enhancing vaccination activities before cold seasons. Further studies are required to fully justify the associations.",2015 Feb 28,"['Chong, Ka Chun', 'Goggins, William', 'Zee, Benny Chung Ying', 'Wang, Maggie Haitian']",Int J Environ Res Public Health,,,False
9718efa7298b28b740938eeca415b1703ec6f689,PMC,Effects of ribavirin on the replication and genetic stability of porcine reproductive and respiratory syndrome virus,http://dx.doi.org/10.1186/s12917-015-0330-z,PMC4344762,25890207,CC BY,"BACKGROUND: Although modified live virus (MLV) vaccines are commonly used for porcine reproductive and respiratory syndrome virus (PRRSV) control, there have been safety concerns due to the quick reversion of MLV to virulence during replication in pigs. Previous studies have demonstrated that mutant viruses emerged from lethal mutagenesis driven by antiviral mutagens and that those viruses had higher genetic stability compared to their parental strains because they acquired resistance to random mutation. Thus, this strategy was explored to stabilize the PRRSV genome in the current study. RESULTS: Four antiviral mutagens (ribavirin, 5-fluorouracil, 5-azacytidine, and amiloride) were evaluated for their antiviral effects against VR2332, a prototype of type 2 PRRSV. Among the mutagens, ribavirin and 5-fluorouracil had significant antiviral effects against VR2332. Consequently, VR2332 was serially passaged in MARC-145 cells in the presence of ribavirin at several concentrations to facilitate the emergence of ribavirin-resistant mutants. Two ribavirin-resistant mutants, RVRp13 and RVRp22, emerged from serial passages in the presence of 0.1 and 0.2 mM ribavirin, respectively. The genetic stability of these resistant mutants was evaluated in MARC-145 cells and compared with VR2332. As expected, the ribavirin-resistant mutants exhibited higher genetic stability compared to their parental virus. CONCLUSIONS: In summary, ribavirin and 5-fluorouracil effectively suppressed PRRSV replication in MARC-145 cells. However, ribavirin-resistant mutants emerged when treated with low concentrations (≤0.2 mM) of ribavirin, and those mutants were genetically more stable during serial passages in cell culture.",2015 Feb 7,"['Khatun, Amina', 'Shabir, Nadeem', 'Yoon, Kyoung-Jin', 'Kim, Won-Il']",BMC Vet Res,,,True
621fb61c827a3f1f0c6c69849319ed45f6dc1f5b,PMC,Viral infections in outpatients with medically attended acute respiratory illness during the 2012–2013 influenza season,http://dx.doi.org/10.1186/s12879-015-0806-2,PMC4344779,25887948,CC BY,"BACKGROUND: While it is known that acute respiratory illness (ARI) is caused by an array of viruses, less is known about co-detections and the resultant comparative symptoms and illness burden. This study examined the co-detections, the distribution of viruses, symptoms, and illness burden associated with ARI between December 2012 and March 2013. METHODS: Outpatients with ARI were assayed for presence of 18 viruses using multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) to simultaneously detect multiple viruses. RESULTS: Among 935 patients, 60% tested positive for a single virus, 9% tested positive for ≥1 virus and 287 (31%) tested negative. Among children (<18 years), the respective distributions were 63%, 14%, and 23%; whereas for younger adults (18–49 years), the distributions were 58%, 8%, and 34% and for older adults (≥50 years) the distributions were 61%, 5%, and 32% (P < 0.001). Co-detections were more common in children than older adults (P = 0.01), and less frequent in households without children (P = 0.003). Most frequently co-detected viruses were coronavirus, respiratory syncytial virus, and influenza A virus. Compared with single viral infections, those with co-detections less frequently reported sore throat (P = 0.01), missed fewer days of school (1.1 vs. 2 days; P = 0.04), or work (2 vs. 3 days; P = 0.03); other measures of illness severity did not vary. CONCLUSIONS: Among outpatients with ARI, 69% of visits were associated with a viral etiology. Co-detections of specific clusters of viruses were observed in 9% of ARI cases particularly in children, were less frequent in households without children, and were less symptomatic (e.g., lower fever) than single infections.",2015 Feb 22,"['Zimmerman, Richard K', 'Rinaldo, Charles R', 'Nowalk, Mary Patricia', 'Balasubramani, GK', 'Moehling, Krissy K', 'Bullotta, Arlene', 'Eng, Heather F', 'Raviotta, Jonathan M', 'Sax, Theresa M', 'Wisniewski, Stephen']",BMC Infect Dis,,,True
78b305688d964809c3cd62063d7fa6ecf30ebbc9,PMC,A multiplex PCR assay for the detection of five influenza viruses using a dual priming oligonucleotide system,http://dx.doi.org/10.1186/s12879-015-0818-y,PMC4344991,25886516,CC BY,"BACKGROUND: A cost-effective, accurate and rapid simultaneous multiplex assay is required for testing and diagnoses of conventional and emerging viruses in clinical virology laboratories. We developed and optimized a dual priming oligonucleotide (DPO) multiplex PCR assay for detecting influenza viruses including seasonal H1N1, 2009 pandemic H1N1, H3N2, influenza B and H5N1. METHODS: The optimized multiplex DPO PCR was used to detect 233 clinical human samples. The results were compared to those obtained with RT-qPCR, conventional PCR and immunochromatographic assay. RESULTS: Specificity analysis revealed that the DPO PCR assay amplified each target virus without any cross-amplification. Statistical analysis demonstrated that the multiplex DPO-PCR sensitivity was higher than for the immunochromatographic assay and lower than for qPCR, while no significant difference was observed compared with conventional PCR, when detecting influenza A and B. Additional experiments using the same sample panel indicated no significant differences between the number of positive samples detected by multiplex DPO PCR and RT-qPCR when applying a Cq with a value lower than 30. CONCLUSIONS: The five-targeted simultaneous multiplex DPO PCR assay could be easily adopted into routine practice. This approach is cost effective with a short running time, low technical requirements for the detection of influenza virus and early diagnosis in clinical laboratories.",2015 Feb 25,"['Ma, Xuezheng', 'Xu, Huanzhou', 'Shi, Lei', 'Yang, Pengfei', 'Zhang, Liping', 'Sun, Xiaohong', 'Zhen, Wei', 'Hu, Kongxin']",BMC Infect Dis,,,True
ffdef5aa153fee8ed2cac3d1434c8ec54a67e1ae,PMC,A Bayesian Inferential Approach to Quantify the Transmission Intensity of Disease Outbreak,http://dx.doi.org/10.1155/2015/256319,PMC4345055,25784956,CC BY,"Background. Emergence of infectious diseases like influenza pandemic (H1N1) 2009 has become great concern, which posed new challenges to the health authorities worldwide. To control these diseases various studies have been developed in the field of mathematical modelling, which is useful tool for understanding the epidemiological dynamics and their dependence on social mixing patterns. Method. We have used Bayesian approach to quantify the disease outbreak through key epidemiological parameter basic reproduction number (R (0)), using effective contacts, defined as sum of the product of incidence cases and probability of generation time distribution. We have estimated R (0) from daily case incidence data for pandemic influenza A/H1N1 2009 in India, for the initial phase. Result. The estimated R (0) with 95% credible interval is consistent with several other studies on the same strain. Through sensitivity analysis our study indicates that infectiousness affects the estimate of R (0). Conclusion. Basic reproduction number R (0) provides the useful information to the public health system to do some effort in controlling the disease by using mitigation strategies like vaccination, quarantine, and so forth.",2015 Feb 15,"['Kadi, Adiveppa S.', 'Avaradi, Shivakumari R.']",Comput Math Methods Med,,,False
b50ee1febe5e4b252cbc70678de7272524377ca1,PMC,A Bayesian Inferential Approach to Quantify the Transmission Intensity of Disease Outbreak,http://dx.doi.org/10.1155/2015/256319,PMC4345055,25784956,CC BY,"Background. Emergence of infectious diseases like influenza pandemic (H1N1) 2009 has become great concern, which posed new challenges to the health authorities worldwide. To control these diseases various studies have been developed in the field of mathematical modelling, which is useful tool for understanding the epidemiological dynamics and their dependence on social mixing patterns. Method. We have used Bayesian approach to quantify the disease outbreak through key epidemiological parameter basic reproduction number (R (0)), using effective contacts, defined as sum of the product of incidence cases and probability of generation time distribution. We have estimated R (0) from daily case incidence data for pandemic influenza A/H1N1 2009 in India, for the initial phase. Result. The estimated R (0) with 95% credible interval is consistent with several other studies on the same strain. Through sensitivity analysis our study indicates that infectiousness affects the estimate of R (0). Conclusion. Basic reproduction number R (0) provides the useful information to the public health system to do some effort in controlling the disease by using mitigation strategies like vaccination, quarantine, and so forth.",2015 Feb 15,"['Kadi, Adiveppa S.', 'Avaradi, Shivakumari R.']",Comput Math Methods Med,,,True
758d365d79d74aee483623c5abeab0c682bf1ad3,PMC,CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production,http://dx.doi.org/10.1038/ncomms7217,PMC4346637,25692415,CC BY,"B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture. Here we show that intrinsic signalling of CEACAM1 is essential for generating efficient B-cell responses. Although CEACAM1 exerts limited influence on the proliferation of B cells, expression of CEACAM1 induces survival of proliferating B cells via the BTK/Syk/NF-κB-axis. The absence of this signalling cascade in naive Ceacam1(−/−) mice limits the survival of B cells. During systemic infection with cytopathic vesicular stomatitis virus, Ceacam1(−/−) mice can barely induce neutralizing antibody responses and die early after infection. We find, therefore, that CEACAM1 is a crucial regulator of B-cell survival, influencing B-cell numbers and protective antiviral antibody responses.",2015 Feb 18,"['Khairnar, Vishal', 'Duhan, Vikas', 'Maney, Sathish Kumar', 'Honke, Nadine', 'Shaabani, Namir', 'Pandyra, Aleksandra A.', 'Seifert, Marc', 'Pozdeev, Vitaly', 'Xu, Haifeng C.', 'Sharma, Piyush', 'Baldin, Fabian', 'Marquardsen, Florian', 'Merches, Katja', 'Lang, Elisabeth', 'Kirschning, Carsten', 'Westendorf, Astrid M.', 'Häussinger, Dieter', 'Lang, Florian', 'Dittmer, Ulf', 'Küppers, Ralf', 'Recher, Mike', 'Hardt, Cornelia', 'Scheffrahn, Inka', 'Beauchemin, Nicole', 'Göthert, Joachim R.', 'Singer, Bernhard B.', 'Lang, Philipp A.', 'Lang, Karl S.']",Nat Commun,,,True
b473fcfb0b124c50f252ea3087dd03e45cd81e29,PMC,CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production,http://dx.doi.org/10.1038/ncomms7217,PMC4346637,25692415,CC BY,"B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture. Here we show that intrinsic signalling of CEACAM1 is essential for generating efficient B-cell responses. Although CEACAM1 exerts limited influence on the proliferation of B cells, expression of CEACAM1 induces survival of proliferating B cells via the BTK/Syk/NF-κB-axis. The absence of this signalling cascade in naive Ceacam1(−/−) mice limits the survival of B cells. During systemic infection with cytopathic vesicular stomatitis virus, Ceacam1(−/−) mice can barely induce neutralizing antibody responses and die early after infection. We find, therefore, that CEACAM1 is a crucial regulator of B-cell survival, influencing B-cell numbers and protective antiviral antibody responses.",2015 Feb 18,"['Khairnar, Vishal', 'Duhan, Vikas', 'Maney, Sathish Kumar', 'Honke, Nadine', 'Shaabani, Namir', 'Pandyra, Aleksandra A.', 'Seifert, Marc', 'Pozdeev, Vitaly', 'Xu, Haifeng C.', 'Sharma, Piyush', 'Baldin, Fabian', 'Marquardsen, Florian', 'Merches, Katja', 'Lang, Elisabeth', 'Kirschning, Carsten', 'Westendorf, Astrid M.', 'Häussinger, Dieter', 'Lang, Florian', 'Dittmer, Ulf', 'Küppers, Ralf', 'Recher, Mike', 'Hardt, Cornelia', 'Scheffrahn, Inka', 'Beauchemin, Nicole', 'Göthert, Joachim R.', 'Singer, Bernhard B.', 'Lang, Philipp A.', 'Lang, Karl S.']",Nat Commun,,,False
8e15c84010f5ea9e602ae6e51f9ac12ee754a9c9,PMC,Ebola Policies That Hinder Epidemic Response by Limiting Scientific Discourse,http://dx.doi.org/10.4269/ajtmh.14-0803,PMC4347321,25561564,CC BY,"There is an unprecedented epidemic of Ebola virus disease (EVD) in west Africa. There has been a strong response from dedicated health professionals. However, there have also been irrational and fear-based responses that have contributed to misallocation of resources, stigma, and deincentivizing volunteers to combat Ebola at its source. Recently, the State of Louisiana Department of Health and Hospitals issued a ban on those coming from affected countries wishing to attend the annual meetings of American Society of Tropical Medicine and Hygiene and the American Public Health Association, both of which were held in New Orleans. We argue against such policies, question evidence and motivations, and discuss their practical and ethical implications in hampering effective responses to EVD by the scientific community. We aim to shed light on this issue and its implications for the future of public health interventions, reflect on the responsibility of health providers and professional societies as advocates for patients and the public health, and call for health professionals and societies to work to challenge inappropriate political responses to public health crises.",2015 Feb 4,"['Asgary, Ramin', 'Pavlin, Julie A.', 'Ripp, Jonathan A.', 'Reithinger, Richard', 'Polyak, Christina S.']",Am J Trop Med Hyg,,,True
11022b299f98034d0060f9c036333f1b9024d7a1,PMC,Evidence of infectivity of airborne porcine epidemic diarrhea virus and detection of airborne viral RNA at long distances from infected herds,http://dx.doi.org/10.1186/s13567-014-0073-z,PMC4347589,25017790,CC BY,"Porcine epidemic diarrhea virus (PEDV) spread rapidly after being diagnosed in the USA in April 2013. In this study we assessed whether PEDV could become airborne and if so, whether the virus was infectious. Air samples were collected both from a room containing experimentally infected pigs and at various distances from the outside of swine farms experiencing acute PEDV outbreaks. Results indicated presence of infectious PEDV in the air from experimentally infected pigs and genetic material of PEDV was detected up to 10 miles downwind from naturally infected farms. Airborne transmission should be considered as a potential route for PEDV dissemination.",2014 Jul 14,"['Alonso, Carmen', 'Goede, Dane P', 'Morrison, Robert B', 'Davies, Peter R', 'Rovira, Albert', 'Marthaler, Douglas G', 'Torremorell, Montserrat']",Vet Res,,,True
46b318ba828af275acaaf75fb723e88980f96043,PMC,Do corticosteroids reduce the mortality of influenza A (H1N1) infection? A meta-analysis,http://dx.doi.org/10.1186/s13054-015-0764-5,PMC4348153,25888424,CC BY,"INTRODUCTION: Corticosteroids are used empirically in influenza A (H1N1) treatment despite lack of clear evidence for effective treatment. This study aims to assess the efficacy of corticosteroids treatment for H1N1 infection. METHODS: Systematic review and meta-analysis were used to estimate the efficacy of corticosteroids for the prevention of mortality in H1N1 infection. Databases searched included MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Clinical Trials and so on, and bibliographies of retrieved articles, from April 2009 to October 2014. We included both cohort studies and case-control studies reported in English or Chinese that compared treatment effects between corticosteroids and non-corticosteroids therapy in inpatients with H1N1 virus infection. Cohort studies employed mortality as outcome, and case-control studies employed deaths as cases and survivors as controls; both were assessed in this meta-analysis. RESULTS: In total twenty-three eligible studies were included. Both cohort studies (nine studies, n = 1,405) and case-control studies (14 studies, n = 4,700) showed a similar trend toward increased mortality (cohort studies relative risk was 1.85 with 95% confidence interval (CI) 1.46 to 2.33; case-control studies odds ratio was 4.22 with 95% CI 3.10 to 5.76). The results from both subgroup analyses and sensitive analyses were consistent with each other, showing that steroid treatment is associated with mortality. However, considering the fact that corticosteroids were tend to be used in sickest case-patients and heterogeneity was observed between studies, we cannot make a solid conclusion. CONCLUSIONS: Available evidence did not support the use of corticosteroids as standard care for patients with severe influenza. We conclude that further research is required. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0764-5) contains supplementary material, which is available to authorized users.",2015 Feb 20,"['Zhang, Yi', 'Sun, Wenjie', 'Svendsen, Erik R', 'Tang, Song', 'MacIntyre, Raina C', 'Yang, Peng', 'Zhang, Daitao', 'Wang, Quanyi']",Crit Care,,,False
29b0c94901ca75a77502042d007037709ecfe199,PMC,Do corticosteroids reduce the mortality of influenza A (H1N1) infection? A meta-analysis,http://dx.doi.org/10.1186/s13054-015-0764-5,PMC4348153,25888424,CC BY,"INTRODUCTION: Corticosteroids are used empirically in influenza A (H1N1) treatment despite lack of clear evidence for effective treatment. This study aims to assess the efficacy of corticosteroids treatment for H1N1 infection. METHODS: Systematic review and meta-analysis were used to estimate the efficacy of corticosteroids for the prevention of mortality in H1N1 infection. Databases searched included MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Clinical Trials and so on, and bibliographies of retrieved articles, from April 2009 to October 2014. We included both cohort studies and case-control studies reported in English or Chinese that compared treatment effects between corticosteroids and non-corticosteroids therapy in inpatients with H1N1 virus infection. Cohort studies employed mortality as outcome, and case-control studies employed deaths as cases and survivors as controls; both were assessed in this meta-analysis. RESULTS: In total twenty-three eligible studies were included. Both cohort studies (nine studies, n = 1,405) and case-control studies (14 studies, n = 4,700) showed a similar trend toward increased mortality (cohort studies relative risk was 1.85 with 95% confidence interval (CI) 1.46 to 2.33; case-control studies odds ratio was 4.22 with 95% CI 3.10 to 5.76). The results from both subgroup analyses and sensitive analyses were consistent with each other, showing that steroid treatment is associated with mortality. However, considering the fact that corticosteroids were tend to be used in sickest case-patients and heterogeneity was observed between studies, we cannot make a solid conclusion. CONCLUSIONS: Available evidence did not support the use of corticosteroids as standard care for patients with severe influenza. We conclude that further research is required. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0764-5) contains supplementary material, which is available to authorized users.",2015 Feb 20,"['Zhang, Yi', 'Sun, Wenjie', 'Svendsen, Erik R', 'Tang, Song', 'MacIntyre, Raina C', 'Yang, Peng', 'Zhang, Daitao', 'Wang, Quanyi']",Crit Care,,,False
dd432e4c91aa16c92de344b4d93df7b4618d42e1,PMC,Do corticosteroids reduce the mortality of influenza A (H1N1) infection? A meta-analysis,http://dx.doi.org/10.1186/s13054-015-0764-5,PMC4348153,25888424,CC BY,"INTRODUCTION: Corticosteroids are used empirically in influenza A (H1N1) treatment despite lack of clear evidence for effective treatment. This study aims to assess the efficacy of corticosteroids treatment for H1N1 infection. METHODS: Systematic review and meta-analysis were used to estimate the efficacy of corticosteroids for the prevention of mortality in H1N1 infection. Databases searched included MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Clinical Trials and so on, and bibliographies of retrieved articles, from April 2009 to October 2014. We included both cohort studies and case-control studies reported in English or Chinese that compared treatment effects between corticosteroids and non-corticosteroids therapy in inpatients with H1N1 virus infection. Cohort studies employed mortality as outcome, and case-control studies employed deaths as cases and survivors as controls; both were assessed in this meta-analysis. RESULTS: In total twenty-three eligible studies were included. Both cohort studies (nine studies, n = 1,405) and case-control studies (14 studies, n = 4,700) showed a similar trend toward increased mortality (cohort studies relative risk was 1.85 with 95% confidence interval (CI) 1.46 to 2.33; case-control studies odds ratio was 4.22 with 95% CI 3.10 to 5.76). The results from both subgroup analyses and sensitive analyses were consistent with each other, showing that steroid treatment is associated with mortality. However, considering the fact that corticosteroids were tend to be used in sickest case-patients and heterogeneity was observed between studies, we cannot make a solid conclusion. CONCLUSIONS: Available evidence did not support the use of corticosteroids as standard care for patients with severe influenza. We conclude that further research is required. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0764-5) contains supplementary material, which is available to authorized users.",2015 Feb 20,"['Zhang, Yi', 'Sun, Wenjie', 'Svendsen, Erik R', 'Tang, Song', 'MacIntyre, Raina C', 'Yang, Peng', 'Zhang, Daitao', 'Wang, Quanyi']",Crit Care,,,False
c6bf0f9e49e8bb42f0a2839b9316611a66626d7d,PMC,Do corticosteroids reduce the mortality of influenza A (H1N1) infection? A meta-analysis,http://dx.doi.org/10.1186/s13054-015-0764-5,PMC4348153,25888424,CC BY,"INTRODUCTION: Corticosteroids are used empirically in influenza A (H1N1) treatment despite lack of clear evidence for effective treatment. This study aims to assess the efficacy of corticosteroids treatment for H1N1 infection. METHODS: Systematic review and meta-analysis were used to estimate the efficacy of corticosteroids for the prevention of mortality in H1N1 infection. Databases searched included MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Clinical Trials and so on, and bibliographies of retrieved articles, from April 2009 to October 2014. We included both cohort studies and case-control studies reported in English or Chinese that compared treatment effects between corticosteroids and non-corticosteroids therapy in inpatients with H1N1 virus infection. Cohort studies employed mortality as outcome, and case-control studies employed deaths as cases and survivors as controls; both were assessed in this meta-analysis. RESULTS: In total twenty-three eligible studies were included. Both cohort studies (nine studies, n = 1,405) and case-control studies (14 studies, n = 4,700) showed a similar trend toward increased mortality (cohort studies relative risk was 1.85 with 95% confidence interval (CI) 1.46 to 2.33; case-control studies odds ratio was 4.22 with 95% CI 3.10 to 5.76). The results from both subgroup analyses and sensitive analyses were consistent with each other, showing that steroid treatment is associated with mortality. However, considering the fact that corticosteroids were tend to be used in sickest case-patients and heterogeneity was observed between studies, we cannot make a solid conclusion. CONCLUSIONS: Available evidence did not support the use of corticosteroids as standard care for patients with severe influenza. We conclude that further research is required. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0764-5) contains supplementary material, which is available to authorized users.",2015 Feb 20,"['Zhang, Yi', 'Sun, Wenjie', 'Svendsen, Erik R', 'Tang, Song', 'MacIntyre, Raina C', 'Yang, Peng', 'Zhang, Daitao', 'Wang, Quanyi']",Crit Care,,,False
334bc72deded9b157e7f7fcc108fe0671cc41b50,PMC,Do corticosteroids reduce the mortality of influenza A (H1N1) infection? A meta-analysis,http://dx.doi.org/10.1186/s13054-015-0764-5,PMC4348153,25888424,CC BY,"INTRODUCTION: Corticosteroids are used empirically in influenza A (H1N1) treatment despite lack of clear evidence for effective treatment. This study aims to assess the efficacy of corticosteroids treatment for H1N1 infection. METHODS: Systematic review and meta-analysis were used to estimate the efficacy of corticosteroids for the prevention of mortality in H1N1 infection. Databases searched included MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Clinical Trials and so on, and bibliographies of retrieved articles, from April 2009 to October 2014. We included both cohort studies and case-control studies reported in English or Chinese that compared treatment effects between corticosteroids and non-corticosteroids therapy in inpatients with H1N1 virus infection. Cohort studies employed mortality as outcome, and case-control studies employed deaths as cases and survivors as controls; both were assessed in this meta-analysis. RESULTS: In total twenty-three eligible studies were included. Both cohort studies (nine studies, n = 1,405) and case-control studies (14 studies, n = 4,700) showed a similar trend toward increased mortality (cohort studies relative risk was 1.85 with 95% confidence interval (CI) 1.46 to 2.33; case-control studies odds ratio was 4.22 with 95% CI 3.10 to 5.76). The results from both subgroup analyses and sensitive analyses were consistent with each other, showing that steroid treatment is associated with mortality. However, considering the fact that corticosteroids were tend to be used in sickest case-patients and heterogeneity was observed between studies, we cannot make a solid conclusion. CONCLUSIONS: Available evidence did not support the use of corticosteroids as standard care for patients with severe influenza. We conclude that further research is required. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0764-5) contains supplementary material, which is available to authorized users.",2015 Feb 20,"['Zhang, Yi', 'Sun, Wenjie', 'Svendsen, Erik R', 'Tang, Song', 'MacIntyre, Raina C', 'Yang, Peng', 'Zhang, Daitao', 'Wang, Quanyi']",Crit Care,,,True
34483f6b88d4999066d631b65cdf0f256d305b6f,PMC,Evaluation and mechanism for outcomes exploration of providing public health care in contract service in Rural China: a multiple-case study with complex adaptive systems design,http://dx.doi.org/10.1186/s12889-015-1540-9,PMC4349463,25880965,CC BY,"BACKGROUND: The Chinese government has increased the funding for public health in 2009 and experimentally applied a contract service policy (could be seen as a counterpart to family medicine) in 15 counties to promote public health services in the rural areas in 2013. The contract service aimed to convert village doctors, who had privately practiced for decades, into general practitioners under the government management, and better control the rampant chronic diseases. This study made a rare attempt to assess the effectiveness of public health services delivered under the contract service policy, explore the influencing mechanism and draw the implications for the policy extension in the future. METHODS: Three pilot counties and a non-pilot one with heterogeneity in economic and health development from east to west of China were selected by a purposive sampling method. The case study methods by document collection, non-participant observation and interviews (including key informant interview and focus group interview) with 84 health providers and 20 demanders in multiple level were applied in this study. A thematic approach was used to compare diverse outcomes and analyze mechanism in the complex adaptive systems framework. RESULTS: Without sufficient incentives, the public health services were not conducted effectively, regardless of the implementation of the contract policy. To appropriately increase the funding for public health by local finance and properly allocate subsidy to village doctors was one of the most effective approaches to stimulate health providers and demanders’ positivity and promote the policy implementation. County health bureaus acted as the most crucial agents among the complex public health systems. Their mental models influenced by the compound and various environments around them led to the diverse outcomes. If they could provide extra incentives and make the contexts of the systems ripe enough for change, the health providers and demanders would be receptive to the transition of the policy. CONCLUSIONS: The innovative fund raising measures could be taken by relatively developed counties of China to conduct public health services. Policymakers could take systems thinking as a useful tool to design plans and predict the unintended outcomes during the process of public health reforms.",2015 Feb 27,"['Zhou, Huixuan', 'Zhang, Shengfa', 'Zhang, Weijun', 'Wang, Fugang', 'Zhong, You', 'Gu, Linni', 'Qu, Zhiyong', 'Tian, Donghua']",BMC Public Health,,,True
7bb2233fecf687276332f5cfe4630d5286966390,PMC,"Improving the large scale purification of the HIV microbicide, griffithsin",http://dx.doi.org/10.1186/s12896-015-0120-5,PMC4349730,25887919,CC BY,"BACKGROUND: Griffithsin is a broad spectrum antiviral lectin that inhibits viral entry and maturation processes through binding clusters of oligomannose glycans on viral envelope glycoproteins. An efficient, scaleable manufacturing process for griffithsin active pharmaceutical ingredient (API) is essential for particularly cost-sensitive products such as griffithsin -based topical microbicides for HIV-1 prevention in resource poor settings. Our previously published purification method used ceramic filtration followed by two chromatography steps, resulting in a protein recovery of 30%. Our objective was to develop a scalable purification method for griffithsin expressed in Nicotiana benthamiana plants that would increase yield, reduce production costs, and simplify manufacturing techniques. Considering the future need to transfer griffithsin manufacturing technology to resource poor areas, we chose to focus modifying the purification process, paying particular attention to introducing simple, low-cost, and scalable procedures such as use of temperature, pH, ion concentration, and filtration to enhance product recovery. RESULTS: We achieved >99% pure griffithsin API by generating the initial green juice extract in pH 4 buffer, heating the extract to 55°C, incubating overnight with a bentonite MgCl(2) mixture, and final purification with Capto™ multimodal chromatography. Griffithsin extracted with this protocol maintains activity comparable to griffithsin purified by the previously published method and we are able to recover a substantially higher yield: 88 ± 5% of griffithsin from the initial extract. The method was scaled to produce gram quantities of griffithsin with high yields, low endotoxin levels, and low purification costs maintained. CONCLUSIONS: The methodology developed to purify griffithsin introduces and develops multiple tools for purification of recombinant proteins from plants at an industrial scale. These tools allow for robust cost-effective production and purification of griffithsin. The methodology can be readily scaled to the bench top or industry and process components can be used for purification of additional proteins based on biophysical characteristics.",2015 Feb 22,"['Fuqua, Joshua L', 'Wanga, Valentine', 'Palmer, Kenneth E']",BMC Biotechnol,,,True
f02529d9be6c7576b60d295c4e04d15a9a432614,PMC,The C-Terminal Sequence of IFITM1 Regulates Its Anti-HIV-1 Activity,http://dx.doi.org/10.1371/journal.pone.0118794,PMC4349745,25738301,CC BY,"The interferon-inducible transmembrane (IFITM) proteins inhibit a wide range of viruses. We previously reported the inhibition of human immunodeficiency virus type 1 (HIV-1) strain BH10 by human IFITM1, 2 and 3. It is unknown whether other HIV-1 strains are similarly inhibited by IFITMs and whether there exists viral countermeasure to overcome IFITM inhibition. We report here that the HIV-1 NL4-3 strain (HIV-1(NL4-3)) is not restricted by IFITM1 and its viral envelope glycoprotein is partly responsible for this insensitivity. However, HIV-1(NL4-3) is profoundly inhibited by an IFITM1 mutant, known as Δ(117–125), which is deleted of 9 amino acids at the C-terminus. In contrast to the wild type IFITM1, which does not affect HIV-1 entry, the Δ(117–125) mutant diminishes HIV-1(NL4-3) entry by 3-fold. This inhibition correlates with the predominant localization of Δ(117–125) to the plasma membrane where HIV-1 entry occurs. In spite of strong conservation of IFITM1 among most species, mouse IFITM1 is 19 amino acids shorter at its C-terminus as compared to human IFITM1 and, like the human IFITM1 mutant Δ(117–125), mouse IFITM1 also inhibits HIV-1 entry. This is the first report illustrating the role of viral envelope protein in overcoming IFITM1 restriction. The results also demonstrate the importance of the C-terminal region of IFITM1 in modulating the antiviral function through controlling protein subcellular localization.",2015 Mar 4,"['Jia, Rui', 'Ding, Shilei', 'Pan, Qinghua', 'Liu, Shan-Lu', 'Qiao, Wentao', 'Liang, Chen']",PLoS One,,,True
62dd39338a12f7b81ae4e79e030c238c9ddaedfe,PMC,A Novel Video Tracking Method to Evaluate the Effect of Influenza Infection and Antiviral Treatment on Ferret Activity,http://dx.doi.org/10.1371/journal.pone.0118780,PMC4349809,25738900,CC BY,"Ferrets are the preferred animal model to assess influenza virus infection, virulence and transmission as they display similar clinical symptoms and pathogenesis to those of humans. Measures of disease severity in the ferret include weight loss, temperature rise, sneezing, viral shedding and reduced activity. To date, the only available method for activity measurement has been the assignment of an arbitrary score by a ‘blind’ observer based on pre-defined responsiveness scale. This manual scoring method is subjective and can be prone to bias. In this study, we described a novel video-tracking methodology for determining activity changes in a ferret model of influenza infection. This method eliminates the various limitations of manual scoring, which include the need for a sole ‘blind’ observer and the requirement to recognise the ‘normal’ activity of ferrets in order to assign relative activity scores. In ferrets infected with an A(H1N1)pdm09 virus, video-tracking was more sensitive than manual scoring in detecting ferret activity changes. Using this video-tracking method, oseltamivir treatment was found to ameliorate the effect of influenza infection on activity in ferret. Oseltamivir treatment of animals was associated with an improvement in clinical symptoms, including reduced inflammatory responses in the upper respiratory tract, lower body weight loss and a smaller rise in body temperature, despite there being no significant reduction in viral shedding. In summary, this novel video-tracking is an easy-to-use, objective and sensitive methodology for measuring ferret activity.",2015 Mar 4,"['Oh, Ding Yuan', 'Barr, Ian G.', 'Hurt, Aeron C.']",PLoS One,,,True
6777d788e99e108bf3439ed5a79ac921ee60d06e,PMC,Endemic zoonoses in the tropics: a public health problem hiding in plain sight,http://dx.doi.org/10.1136/vr.h798,PMC4350138,25722334,CC BY,"Zoonotic diseases are a significant burden on animal and human health, particularly in developing countries. Despite recognition of this fact, endemic zoonoses often remain undiagnosed in people, instead being mistaken for febrile diseases such as malaria. Here, as part of Veterinary Record's ongoing series of articles on One Health, a multidisciplinary team of researchers from Scotland, Tanzania and New Zealand argues that a One Health approach is needed to effectively combat these diseases",2015 Feb 28,"['Halliday, Jo E. B.', 'Allan, Kathryn J.', 'Ekwem, Divine', 'Cleaveland, Sarah', 'Kazwala, Rudovick R.', 'Crump, John A.']",Vet Rec,,,True
0093f9ae0861afc0d29fff935ae6a3af898cea00,PMC,Emergence of infectious malignant thrombocytopenia in Japanese macaques (Macaca fuscata) by SRV-4 after transmission to a novel host,http://dx.doi.org/10.1038/srep08850,PMC4351523,25743183,CC BY,"We discovered a lethal hemorrhagic syndrome arising from severe thrombocytopenia in Japanese macaques kept at the Primate Research Institute, Kyoto University. Extensive investigation identified that simian retrovirus type 4 (SRV-4) was the causative agent of the disease. SRV-4 had previously been isolated only from cynomolgus macaques in which it is usually asymptomatic. We consider that the SRV-4 crossed the so-called species barrier between cynomolgus and Japanese macaques, leading to extremely severe acute symptoms in the latter. Infectious agents that cross the species barrier occasionally amplify in virulence, which is not observed in the original hosts. In such cases, the new hosts are usually distantly related to the original hosts. However, Japanese macaques are closely related to cynomolgus macaques, and can even hybridize when given the opportunity. This lethal outbreak of a novel pathogen in Japanese macaques highlights the need to modify our expectations about virulence with regards crossing species barriers.",2015 Mar 6,"['Okamoto, Munehiro', 'Miyazawa, Takayuki', 'Morikawa, Shigeru', 'Ono, Fumiko', 'Nakamura, Shota', 'Sato, Eiji', 'Yoshida, Tomoyuki', 'Yoshikawa, Rokusuke', 'Sakai, Kouji', 'Mizutani, Tetsuya', 'Nagata, Noriyo', 'Takano, Jun-ichiro', 'Okabayashi, Sachi', 'Hamano, Masataka', 'Fujimoto, Koji', 'Nakaya, Takaaki', 'Iida, Tetsuya', 'Horii, Toshihiro', 'Miyabe-Nishiwaki, Takako', 'Watanabe, Akino', 'Kaneko, Akihisa', 'Saito, Akatsuki', 'Matsui, Atsushi', 'Hayakawa, Toshiyuki', 'Suzuki, Juri', 'Akari, Hirofumi', 'Matsuzawa, Tetsuro', 'Hirai, Hirohisa']",Sci Rep,,,True
d2c64d81f9871f7b84cc90c81069098630e30dc4,PMC,Emergence of infectious malignant thrombocytopenia in Japanese macaques (Macaca fuscata) by SRV-4 after transmission to a novel host,http://dx.doi.org/10.1038/srep08850,PMC4351523,25743183,CC BY,"We discovered a lethal hemorrhagic syndrome arising from severe thrombocytopenia in Japanese macaques kept at the Primate Research Institute, Kyoto University. Extensive investigation identified that simian retrovirus type 4 (SRV-4) was the causative agent of the disease. SRV-4 had previously been isolated only from cynomolgus macaques in which it is usually asymptomatic. We consider that the SRV-4 crossed the so-called species barrier between cynomolgus and Japanese macaques, leading to extremely severe acute symptoms in the latter. Infectious agents that cross the species barrier occasionally amplify in virulence, which is not observed in the original hosts. In such cases, the new hosts are usually distantly related to the original hosts. However, Japanese macaques are closely related to cynomolgus macaques, and can even hybridize when given the opportunity. This lethal outbreak of a novel pathogen in Japanese macaques highlights the need to modify our expectations about virulence with regards crossing species barriers.",2015 Mar 6,"['Okamoto, Munehiro', 'Miyazawa, Takayuki', 'Morikawa, Shigeru', 'Ono, Fumiko', 'Nakamura, Shota', 'Sato, Eiji', 'Yoshida, Tomoyuki', 'Yoshikawa, Rokusuke', 'Sakai, Kouji', 'Mizutani, Tetsuya', 'Nagata, Noriyo', 'Takano, Jun-ichiro', 'Okabayashi, Sachi', 'Hamano, Masataka', 'Fujimoto, Koji', 'Nakaya, Takaaki', 'Iida, Tetsuya', 'Horii, Toshihiro', 'Miyabe-Nishiwaki, Takako', 'Watanabe, Akino', 'Kaneko, Akihisa', 'Saito, Akatsuki', 'Matsui, Atsushi', 'Hayakawa, Toshiyuki', 'Suzuki, Juri', 'Akari, Hirofumi', 'Matsuzawa, Tetsuro', 'Hirai, Hirohisa']",Sci Rep,,,False
035dfb6e2398c95bbf6b65db97b443908a43e093,PMC,RIEMS: a software pipeline for sensitive and comprehensive taxonomic classification of reads from metagenomics datasets,http://dx.doi.org/10.1186/s12859-015-0503-6,PMC4351923,25886935,CC BY,"BACKGROUND: Fuelled by the advent and subsequent development of next generation sequencing technologies, metagenomics became a powerful tool for the analysis of microbial communities both scientifically and diagnostically. The biggest challenge is the extraction of relevant information from the huge sequence datasets generated for metagenomics studies. Although a plethora of tools are available, data analysis is still a bottleneck. RESULTS: To overcome the bottleneck of data analysis, we developed an automated computational workflow called RIEMS – Reliable Information Extraction from Metagenomic Sequence datasets. RIEMS assigns every individual read sequence within a dataset taxonomically by cascading different sequence analyses with decreasing stringency of the assignments using various software applications. After completion of the analyses, the results are summarised in a clearly structured result protocol organised taxonomically. The high accuracy and performance of RIEMS analyses were proven in comparison with other tools for metagenomics data analysis using simulated sequencing read datasets. CONCLUSIONS: RIEMS has the potential to fill the gap that still exists with regard to data analysis for metagenomics studies. The usefulness and power of RIEMS for the analysis of genuine sequencing datasets was demonstrated with an early version of RIEMS in 2011 when it was used to detect the orthobunyavirus sequences leading to the discovery of Schmallenberg virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0503-6) contains supplementary material, which is available to authorized users.",2015 Mar 3,"['Scheuch, Matthias', 'Höper, Dirk', 'Beer, Martin']",BMC Bioinformatics,,,True
a8f7ee410837cdbf7f974543e432d161fb70cd11,PMC,"The Role of Misshapen NCK-related kinase (MINK), a Novel Ste20 Family Kinase, in the IRES-Mediated Protein Translation of Human Enterovirus 71",http://dx.doi.org/10.1371/journal.ppat.1004686,PMC4352056,25747578,CC BY,"Human Enterovirus 71 (EV71) commonly causes Hand, Foot and Mouth Disease in young children, and occasional occurrences of neurological complications can be fatal. In this study, a high-throughput cell-based screening on the serine/threonine kinase siRNA library was performed to identify potential antiviral agents against EV71 replication. Among the hits, Misshapen/NIKs-related kinase (MINK) was selected for detailed analysis due to its strong inhibitory profile and novelty. In the investigation of the stage at which MINK is involved in EV71 replication, virus RNA transfection in MINK siRNA-treated cells continued to cause virus inhibition despite bypassing the normal entry pathway, suggesting its involvement at the post-entry stage. We have also shown that viral RNA and protein expression level was significantly reduced upon MINK silencing, suggesting its involvement in viral protein synthesis which feeds into viral RNA replication process. Through proteomic analysis and infection inhibition assay, we found that the activation of MINK was triggered by early replication events, instead of the binding and entry of the virus. Proteomic analysis on the activation profile of p38 Mitogen-activated Protein Kinase (MAPK) indicated that the phosphorylation of p38 MAPK was stimulated by EV71 infection upon MINK activation. Luciferase reporter assay further revealed that the translation efficiency of the EV71 internal ribosomal entry site (IRES) was reduced after blocking the MINK/p38 MAPK pathway. Further investigation on the effect of MINK silencing on heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) localisation demonstrated that cytoplasmic relocalisation of hnRNP A1 upon EV71 infection may be facilitated via the MINK/p38 MAPK pathway which then positively regulates the translation of viral RNA transcripts. These novel findings hence suggest that MINK plays a functional role in the IRES-mediated translation of EV71 viral RNA and may provide a potential target for the development of specific antiviral strategies against EV71 infection.",2015 Mar 6,"['Leong, Shi Yun', 'Ong, Bryan Kit Teck', 'Chu, Justin Jang Hann']",PLoS Pathog,,,True
3ecefecb6bd94b90680980f6d67045f7536d3410,PMC,Constant up-regulation of BiP/GRP78 expression prevents virus-induced apoptosis in BHK-21 cells with Japanese encephalitis virus persistent infection,http://dx.doi.org/10.1186/s12985-015-0269-5,PMC4352245,25888736,CC BY,"BACKGROUND: Persistent infection of the Japanese Encephalitis Virus (JEV) has been reported in clinical cases, experimental animals, and various cell culture systems. We previously reported the establishment of spontaneous JEV persistent infection, assisted by defective interfering particle accumulation and/or attenuated helper viruses, in BHK-21 cells devoid of virus-induced apoptosis, cBS6-2 and cBS6-3. However, cell-specific factors may play important roles in controlling JEV replication and have never been assessed for this specific phenomenon. Recent evidence suggests that viruses have evolved various mechanisms to cope with endoplasmic reticulum stress signaling pathways for their efficient amplification and transmission, including the unfolded protein response (UPR). RESULTS: To identify the host cell factors that affect JEV persistence, we investigated the expression of essential UPR factors in cBS6-2 and cBS6-3 cells. Of the selected UPR factors tested, the most noticeable deviations from those of the normal BHK-21 cells with JEV acute infection were as follows: the suppression of C/EBP homologous binding protein (CHOP) and the constant up-regulation of immunoglobulin binding protein (BiP) expression in cBS6-2 and cBS6-3 cells. In JEV acute infection on normal BHK-21 cells, silencing CHOP expression through specific siRNA blocked cell death almost completely. Meanwhile, depletion of BiP by specific siRNA unlocked CHOP expression in cBS6-2 and cBS6-3 cells, resulting in massive cell death. Fulminant apoptotic cell death for both cell clones on tunicamycin treatment revealed that the JEV persistently infected cells still contained functional arms for cell fate decisions. CONCLUSIONS: BHK-21 cells with JEV persistent infection strive against virus-induced apoptosis through constant up-regulation of BiP expression, resulting in the complete depletion of CHOP even with apparent virus amplification in the cells. Accordingly, the attenuation of virus replication as well as the modifications to cell metabolism could be additional factors contributing to the development of JEV persistent infection in mammalian cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0269-5) contains supplementary material, which is available to authorized users.",2015 Feb 26,"['Lyoo, Hey Rhyoung', 'Park, Soo Young', 'Kim, Ji Young', 'Jeong, Yong Seok']",Virol J,,,False
3b9aeb17bc120925271e7443ebaa19f69ed34a25,PMC,Constant up-regulation of BiP/GRP78 expression prevents virus-induced apoptosis in BHK-21 cells with Japanese encephalitis virus persistent infection,http://dx.doi.org/10.1186/s12985-015-0269-5,PMC4352245,25888736,CC BY,"BACKGROUND: Persistent infection of the Japanese Encephalitis Virus (JEV) has been reported in clinical cases, experimental animals, and various cell culture systems. We previously reported the establishment of spontaneous JEV persistent infection, assisted by defective interfering particle accumulation and/or attenuated helper viruses, in BHK-21 cells devoid of virus-induced apoptosis, cBS6-2 and cBS6-3. However, cell-specific factors may play important roles in controlling JEV replication and have never been assessed for this specific phenomenon. Recent evidence suggests that viruses have evolved various mechanisms to cope with endoplasmic reticulum stress signaling pathways for their efficient amplification and transmission, including the unfolded protein response (UPR). RESULTS: To identify the host cell factors that affect JEV persistence, we investigated the expression of essential UPR factors in cBS6-2 and cBS6-3 cells. Of the selected UPR factors tested, the most noticeable deviations from those of the normal BHK-21 cells with JEV acute infection were as follows: the suppression of C/EBP homologous binding protein (CHOP) and the constant up-regulation of immunoglobulin binding protein (BiP) expression in cBS6-2 and cBS6-3 cells. In JEV acute infection on normal BHK-21 cells, silencing CHOP expression through specific siRNA blocked cell death almost completely. Meanwhile, depletion of BiP by specific siRNA unlocked CHOP expression in cBS6-2 and cBS6-3 cells, resulting in massive cell death. Fulminant apoptotic cell death for both cell clones on tunicamycin treatment revealed that the JEV persistently infected cells still contained functional arms for cell fate decisions. CONCLUSIONS: BHK-21 cells with JEV persistent infection strive against virus-induced apoptosis through constant up-regulation of BiP expression, resulting in the complete depletion of CHOP even with apparent virus amplification in the cells. Accordingly, the attenuation of virus replication as well as the modifications to cell metabolism could be additional factors contributing to the development of JEV persistent infection in mammalian cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0269-5) contains supplementary material, which is available to authorized users.",2015 Feb 26,"['Lyoo, Hey Rhyoung', 'Park, Soo Young', 'Kim, Ji Young', 'Jeong, Yong Seok']",Virol J,,,True
c32c7f59bd902e4b2ef9fbe78e87c1d683de2d42,PMC,Novel adenovirus detected in captive bottlenose dolphins (Tursiops truncatus) suffering from self-limiting gastroenteritis,http://dx.doi.org/10.1186/s12917-015-0367-z,PMC4352565,25888777,CC BY,"BACKGROUND: Adenoviruses are common pathogens in vertebrates, including humans. In marine mammals, adenovirus has been associated with fatal hepatitis in sea lions. However, only in rare cases have adenoviruses been detected in cetaceans, where no clear correlation was found between presence of the virus and disease status. CASE PRESENTATION: A novel adenovirus was identified in four captive bottlenose dolphins with self-limiting gastroenteritis. Viral detection and identification were achieved by: PCR-amplification from fecal samples; sequencing of partial adenovirus polymerase (pol) and hexon genes; producing the virus in HeLa cells, with PCR and immunofluorescence detection, and with sequencing of the amplified pol and hexon gene fragments. A causative role of this adenovirus for gastroenteritis was suggested by: 1) we failed to identify other potential etiological agents; 2) the exclusive detection of this novel adenovirus and of seropositivity for canine adenoviruses 1 and 2 in the four sick dolphins, but not in 10 healthy individuals of the same captive population; and 3) the virus disappeared from feces after clinical signs receded. The partial sequences of the amplified fragments of the pol and hexon genes were closest to those of adenoviruses identified in sea lions with fatal adenoviral hepatitis, and to a Genbank-deposited sequence obtained from a harbour porpoise. CONCLUSION: These data suggest that adenovirus can cause self-limiting gastroenteritis in dolphins. This adenoviral infection can be detected by serology and by PCR detection in fecal material. Lack of signs of hepatitis in sick dolphins may reflect restricted tissue tropism or virulence of this adenovirus compared to those of the adenovirus identified in sea lions. Gene sequence-based phylogenetic analysis supports a common origin of adenoviruses that affect sea mammals. Our findings suggest the need for vigilance against adenoviruses in captive and wild dolphin populations.",2015 Mar 7,"['Rubio-Guerri, Consuelo', 'García-Párraga, Daniel', 'Nieto-Pelegrín, Elvira', 'Melero, Mar', 'Álvaro, Teresa', 'Valls, Mónica', 'Crespo, Jose Luis', 'Sánchez-Vizcaíno, Jose Manuel']",BMC Vet Res,,,True
589045646462acd78b115142b5464cca998f26d7,PMC,Src inhibitor reduces permeability without disturbing vascularization and prevents bone destruction in steroid-associated osteonecrotic lesions in rabbits,http://dx.doi.org/10.1038/srep08856,PMC4352921,25748225,CC BY,"To examine the therapeutic effect of Src inhibitor on the VEGF mediating vascular hyperpermeability and bone destruction within steroid-associated osteonecrotic lesions in rabbits. Rabbits with high risk for progress to destructive repair in steroid-associated osteonecrosis were selected according to our published protocol. The selected rabbits were systemically administrated with either Anti-VEGF antibody (Anti-VEGF Group) or Src inhibitor (Src-Inhibition Group) or VEGF (VEGF-Supplement Group) or a combination of VEGF and Src inhibitor (Supplement & Inhibition Group) or control vehicle (Control Group) for 4 weeks. At 0, 2 and 4 weeks after administration, in vivo dynamic MRI, micro-CT based-angiography, histomorphometry and immunoblotting were employed to evaluate the vascular and skeletal events in different groups. The incidence of the destructive repair in the Anti-VEGF Group, Src-Inhibition Group and Supplement & Inhibition Group was all significantly lower than that in the Control Group. The angiogenesis was promoted in VEGF-Supplement Group, Src-Inhibition Group and Supplement & Inhibition Group, while the hyperpermeability was inhibited in Anti-VEGF Group, Src-Inhibition Group and Supplement & Inhibition Group. The trabecular structure was improved in Src-Inhibition Group and Supplement & Inhibition Group. Src inhibitor could reduce permeability without disturbing vascularization and prevent destructive repair in steroid-associated osteonecrosis.",2015 Mar 9,"['He, Yi-Xin', 'Liu, Jin', 'Guo, Baosheng', 'Wang, Yi-Xiang', 'Pan, Xiaohua', 'Li, Defang', 'Tang, Tao', 'Chen, Yang', 'Peng, Songlin', 'Bian, Zhaoxiang', 'Liang, Zicai', 'Zhang, Bao-Ting', 'Lu, Aiping', 'Zhang, Ge']",Sci Rep,,,True
9146df7c1faca31203b1e903f59662067faebb69,PMC,Sparse evidence of MERS-CoV infection among animal workers living in Southern Saudi Arabia during 2012,http://dx.doi.org/10.1111/irv.12287,PMC4353318,25470665,CC BY,Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging viral pathogen that primarily causes respiratory illness. We conducted a seroprevalence study of banked human serum samples collected in 2012 from Southern Saudi Arabia. Sera from 300 animal workers (17% with daily camel exposure) and 50 non-animal-exposed controls were examined for serological evidence of MERS-CoV infection by a pseudoparticle MERS-CoV spike protein neutralization assay. None of the sera reproducibly neutralized the MERS-CoV-pseudotyped lentiviral vector. These data suggest that serological evidence of zoonotic transmission of MERS-CoV was not common among animal workers in Southern Saudi Arabia during July 2012.,2015 Mar 3,"['Memish, Ziad A', 'Alsahly, Ahmad', 'Masri, Malak al', 'Heil, Gary L', 'Anderson, Benjamin D', 'Peiris, Malik', 'Khan, Salah Uddin', 'Gray, Gregory C']",Influenza Other Respir Viruses,,,True
ca13097c0bc4ca9abed010fa69c56531749da4dd,PMC,Zanamivir versus trivalent split virus influenza vaccine: a pilot randomized trial,http://dx.doi.org/10.1111/irv.12301,PMC4353320,25557838,CC BY,"BACKGROUND: Healthcare workers may be exposed to people with respiratory viral infections more often than other working adults. Understanding the risk and the effectiveness of different preventive measures is of great importance. OBJECTIVES: To estimate adherence to prophylactic antiviral medication for a full influenza season, to the compare efficacy of antiviral prophylaxis to that of the seasonal influenza vaccine and to identify exposures that increase risk of acute respiratory illnesses (ARI) in healthy adults. METHODS: Participants were randomized 1:2 to receive the 2008–2009 influenza vaccine or daily prophylaxis with 10 mg of zanamivir during the season. Web-based questionnaires collected information on demographics, symptoms, exposures, medication use and side effects. RESULTS: Sixty-four healthy adults were recruited in November 2008. Three of 40 active participants discontinued zanamivir due to side effects; the remaining 37 took >85% of scheduled doses for a median of 121 days. Symptomatic, laboratory-confirmed influenza was detected in one person randomized to zanamivir (2·5%) and 2/20 (10%) who received the vaccine (P = 0·25). Forty-seven participants reported 109 episodes of ARI. Factors associated with an ARI were exposure to a spouse (OR 7·2), child (OR 2·4) or patient (OR 2·0) with symptoms of an ARI in the previous 7 days. CONCLUSIONS: Breakthrough influenza infection occurred in both vaccinated participants and those receiving antiviral prophylaxis. Most adults were willing and able to comply with season-long prophylaxis. Report of recent exposure to family members and patients with an ARI increased the risk of developing an ARI in healthy adults.",2015 Mar 4,"['Coleman, Brenda L', 'Fadel, Shaza A', 'Drews, Steven J', 'Hatchette, Todd F', 'McGeer, Allison J']",Influenza Other Respir Viruses,,,True
5d6c145129db8973b797726818f229dfaa997f11,PMC,Prevalence and Correlation of Infectious Agents in Hospitalized Children with Acute Respiratory Tract Infections in Central China,http://dx.doi.org/10.1371/journal.pone.0119170,PMC4353725,25751402,CC BY,"Acute respiratory tract infections (ARTIs) are associated with significant morbidity and mortality worldwide, especially in children under the age of 5 years. Almost 2 million children die from ARTIs each year, and most of them are from developing countries. The prevalence and correlation of pathogens in ARTIs are poorly understood, but are critical for improving case prevention, treatment, and management. In this study, we investigated the prevalence and correlation of infectious agents in children with ARTIs. A total of 39,756 children with one or more symptoms, including fever, cough, sore throat, tonsillitis, pharyngitis, herpangina, pneumonia, and bronchiolitis, were enrolled in the study. All patients were hospitalized in Wuhan Children’s Hospital between October 1, 2010 and September 30, 2012, and were evaluated for infectious agents. Pathogens, including Mycoplasma pneumoniae, influenza A virus, influenza B virus, adenoviruses, respiratory syncytial virus, parainfluenza virus, Legionella pneumophila, Chlamydophila pneumoniae, and Coxiella burnetii, were screened simultaneously in patient blood samples using anti-pathogen IgM tests. Regression analysis was used to reveal correlations among the pathogens. Our results showed that one or more pathogens were identified in 10,206 patients, and that Mycoplasma pneumoniae, adenoviruses, and influenza B virus were the leading infectious agents. Mixed-infections of pathogens were detected in 2,391 cases, with Mycoplasma pneumoniae as the most frequent pathogen. The most common agents in the co-infections were Mycoplasma pneumoniae and influenza B virus. Regression analysis revealed a linear correlation between the proportion of mixed infections and the incidence of multi-pathogen infections. The prevalence of infectious agents in children with ARTIs was determined. Equations were established to estimate multiple infections by single-pathogen detection. This revealed a linear correlation for pathogens in children with ARTIs. This study provides useful information for improving case prevention and management.",2015 Mar 9,"['Liu, Jia', 'Ai, Hongwu', 'Xiong, Ying', 'Li, Fu', 'Wen, Zhou', 'Liu, Weiyong', 'Li, Tongya', 'Qin, Kai', 'Wu, Jianguo', 'Liu, Yingle']",PLoS One,,,True
869eacf84d79a5b176e43988c2dea3be54f6b2ca,PMC,Survival of influenza A virus on contaminated student clothing,http://dx.doi.org/10.3892/etm.2015.2278,PMC4353734,25780410,CC BY,"The role of contaminated clothing in the transmission of influenza A virus during an epidemic period was investigated by examining the recovery of infectious influenza virus from experimentally virus-contaminated clothing, which had been subejected to routine wearing and washing for several months or years. The amount of infectious virus recovered from the nine types of clothing decreased with time and was shown to differ widely between clothing samples, when the contaminated clothing samples were maintained in uncovered glass Petri dishes in a safety cabinet under air blowing. These results indicate a dependence of virus transmissibility on the nature of the contaminated clothes. The difference in recovery was shown to have no significant correlation with the thickness or the materials of the clothing; however, a correlation was observed with the residual amount of water in the deposited virus preparation on the test clothing.",2015 Apr 9,"['IKEDA, KEIKO', 'TSUJIMOTO, KAZUKO', 'SUZUKI, YUKIKO', 'KOYAMA, AUGUSTINE HAJIME']",Exp Ther Med,,,True
2125de45b1af162d3500c2c33c85f33558a7c5e2,PMC,A Micropolymorphism Altering the Residue Triad 97/114/156 Determines the Relative Levels of Tapasin Independence and Distinct Peptide Profiles for HLA-A(*)24 Allotypes,http://dx.doi.org/10.1155/2014/298145,PMC4353853,25802875,CC BY,"While many HLA class I molecules interact directly with the peptide loading complex (PLC) for conventional loading of peptides certain class I molecules are able to present peptides in a way that circumvents the PLC components. We investigated micropolymorphisms at position 156 of HLA-A(*)24 allotypes and their effects on PLC dependence for assembly and peptide binding specificities. HLA-A(*)24:06(156Trp) and HLA-A(*)24:13(156Leu) showed high levels of cell surface expression while HLA-A(*)24:02(156Gln) was expressed at low levels in tapasin deficient cells. Peptides presented by these allelic variants showed distinct differences in features and repertoire. Immunoprecipitation experiments demonstrated all the HLA-A(*)24/156 variants to associate at similar levels with tapasin when present. Structurally, HLA-A(*)24:02 contains the residue triad Met97/His114/Gln156 and a Trp156 or Leu156 polymorphism provides tapasin independence by stabilizing these triad residues, thus generating an energetically stable and a more peptide receptive environment. Micropolymorphisms at position 156 can influence the generic peptide loading pathway for HLA-A(*)24 by altering their tapasin dependence for peptide selection. The trade-off for this tapasin independence could be the presentation of unusual ligands by these alleles, imposing significant risk following hematopoietic stem cell transplantation (HSCT).",2014 Dec 4,"['Badrinath, Soumya', 'Kunze-Schumacher, Heike', 'Blasczyk, Rainer', 'Huyton, Trevor', 'Bade-Doeding, Christina']",J Immunol Res,,,False
c08e4437d35ae6cdbeae2993e4a2264258f3431e,PMC,A Micropolymorphism Altering the Residue Triad 97/114/156 Determines the Relative Levels of Tapasin Independence and Distinct Peptide Profiles for HLA-A(*)24 Allotypes,http://dx.doi.org/10.1155/2014/298145,PMC4353853,25802875,CC BY,"While many HLA class I molecules interact directly with the peptide loading complex (PLC) for conventional loading of peptides certain class I molecules are able to present peptides in a way that circumvents the PLC components. We investigated micropolymorphisms at position 156 of HLA-A(*)24 allotypes and their effects on PLC dependence for assembly and peptide binding specificities. HLA-A(*)24:06(156Trp) and HLA-A(*)24:13(156Leu) showed high levels of cell surface expression while HLA-A(*)24:02(156Gln) was expressed at low levels in tapasin deficient cells. Peptides presented by these allelic variants showed distinct differences in features and repertoire. Immunoprecipitation experiments demonstrated all the HLA-A(*)24/156 variants to associate at similar levels with tapasin when present. Structurally, HLA-A(*)24:02 contains the residue triad Met97/His114/Gln156 and a Trp156 or Leu156 polymorphism provides tapasin independence by stabilizing these triad residues, thus generating an energetically stable and a more peptide receptive environment. Micropolymorphisms at position 156 can influence the generic peptide loading pathway for HLA-A(*)24 by altering their tapasin dependence for peptide selection. The trade-off for this tapasin independence could be the presentation of unusual ligands by these alleles, imposing significant risk following hematopoietic stem cell transplantation (HSCT).",2014 Dec 4,"['Badrinath, Soumya', 'Kunze-Schumacher, Heike', 'Blasczyk, Rainer', 'Huyton, Trevor', 'Bade-Doeding, Christina']",J Immunol Res,,,True
d708b6876813c3915edcbdda08c014d90ec694ab,PMC,Setting healthcare priorities in hospitals: a review of empirical studies,http://dx.doi.org/10.1093/heapol/czu010,PMC4353893,24604831,CC BY,"Priority setting research has focused on the macro (national) and micro (bedside) level, leaving the meso (institutional, hospital) level relatively neglected. This is surprising given the key role that hospitals play in the delivery of healthcare services and the large proportion of health systems resources that they absorb. To explore the factors that impact upon priority setting at the hospital level, we conducted a thematic review of empirical studies. A systematic search of PubMed, EBSCOHOST, Econlit databases and Google scholar was supplemented by a search of key websites and a manual search of relevant papers’ reference lists. A total of 24 papers were identified from developed and developing countries. We applied a policy analysis framework to examine and synthesize the findings of the selected papers. Findings suggest that priority setting practice in hospitals was influenced by (1) contextual factors such as decision space, resource availability, financing arrangements, availability and use of information, organizational culture and leadership, (2) priority setting processes that depend on the type of priority setting activity, (3) content factors such as priority setting criteria and (4) actors, their interests and power relations. We observe that there is need for studies to examine these issues and the interplay between them in greater depth and propose a conceptual framework that might be useful in examining priority setting practices in hospitals.",2015 Apr 5,"['Barasa, Edwine W', 'Molyneux, Sassy', 'English, Mike', 'Cleary, Susan']",Health Policy Plan,,,True
6a83b934090801454dc8e81a559ea4c20c0ef3c7,PMC,Setting healthcare priorities in hospitals: a review of empirical studies,http://dx.doi.org/10.1093/heapol/czu010,PMC4353893,24604831,CC BY,"Priority setting research has focused on the macro (national) and micro (bedside) level, leaving the meso (institutional, hospital) level relatively neglected. This is surprising given the key role that hospitals play in the delivery of healthcare services and the large proportion of health systems resources that they absorb. To explore the factors that impact upon priority setting at the hospital level, we conducted a thematic review of empirical studies. A systematic search of PubMed, EBSCOHOST, Econlit databases and Google scholar was supplemented by a search of key websites and a manual search of relevant papers’ reference lists. A total of 24 papers were identified from developed and developing countries. We applied a policy analysis framework to examine and synthesize the findings of the selected papers. Findings suggest that priority setting practice in hospitals was influenced by (1) contextual factors such as decision space, resource availability, financing arrangements, availability and use of information, organizational culture and leadership, (2) priority setting processes that depend on the type of priority setting activity, (3) content factors such as priority setting criteria and (4) actors, their interests and power relations. We observe that there is need for studies to examine these issues and the interplay between them in greater depth and propose a conceptual framework that might be useful in examining priority setting practices in hospitals.",2015 Apr 5,"['Barasa, Edwine W', 'Molyneux, Sassy', 'English, Mike', 'Cleary, Susan']",Health Policy Plan,,,False
af87680b269c20b507060a20c8dca7e986880e4c,PMC,Setting healthcare priorities in hospitals: a review of empirical studies,http://dx.doi.org/10.1093/heapol/czu010,PMC4353893,24604831,CC BY,"Priority setting research has focused on the macro (national) and micro (bedside) level, leaving the meso (institutional, hospital) level relatively neglected. This is surprising given the key role that hospitals play in the delivery of healthcare services and the large proportion of health systems resources that they absorb. To explore the factors that impact upon priority setting at the hospital level, we conducted a thematic review of empirical studies. A systematic search of PubMed, EBSCOHOST, Econlit databases and Google scholar was supplemented by a search of key websites and a manual search of relevant papers’ reference lists. A total of 24 papers were identified from developed and developing countries. We applied a policy analysis framework to examine and synthesize the findings of the selected papers. Findings suggest that priority setting practice in hospitals was influenced by (1) contextual factors such as decision space, resource availability, financing arrangements, availability and use of information, organizational culture and leadership, (2) priority setting processes that depend on the type of priority setting activity, (3) content factors such as priority setting criteria and (4) actors, their interests and power relations. We observe that there is need for studies to examine these issues and the interplay between them in greater depth and propose a conceptual framework that might be useful in examining priority setting practices in hospitals.",2015 Apr 5,"['Barasa, Edwine W', 'Molyneux, Sassy', 'English, Mike', 'Cleary, Susan']",Health Policy Plan,,,False
bdf348d6be154ebbd7acda6e7ff4ebcf66277708,PMC,Setting healthcare priorities in hospitals: a review of empirical studies,http://dx.doi.org/10.1093/heapol/czu010,PMC4353893,24604831,CC BY,"Priority setting research has focused on the macro (national) and micro (bedside) level, leaving the meso (institutional, hospital) level relatively neglected. This is surprising given the key role that hospitals play in the delivery of healthcare services and the large proportion of health systems resources that they absorb. To explore the factors that impact upon priority setting at the hospital level, we conducted a thematic review of empirical studies. A systematic search of PubMed, EBSCOHOST, Econlit databases and Google scholar was supplemented by a search of key websites and a manual search of relevant papers’ reference lists. A total of 24 papers were identified from developed and developing countries. We applied a policy analysis framework to examine and synthesize the findings of the selected papers. Findings suggest that priority setting practice in hospitals was influenced by (1) contextual factors such as decision space, resource availability, financing arrangements, availability and use of information, organizational culture and leadership, (2) priority setting processes that depend on the type of priority setting activity, (3) content factors such as priority setting criteria and (4) actors, their interests and power relations. We observe that there is need for studies to examine these issues and the interplay between them in greater depth and propose a conceptual framework that might be useful in examining priority setting practices in hospitals.",2015 Apr 5,"['Barasa, Edwine W', 'Molyneux, Sassy', 'English, Mike', 'Cleary, Susan']",Health Policy Plan,,,False
ad04f777044b7de892dbc174e31e88e63a160c3c,PMC,Aptamers in Diagnostics and Treatment of Viral Infections,http://dx.doi.org/10.3390/v7020751,PMC4353915,25690797,CC BY,"Aptamers are in vitro selected DNA or RNA molecules that are capable of binding a wide range of nucleic and non-nucleic acid molecules with high affinity and specificity. They have been conducted through the process known as SELEX (Systematic Evolution of Ligands by Exponential Enrichment). It serves to reach specificity and considerable affinity to target molecules, including those of viral origin, both proteins and nucleic acids. Properties of aptamers allow detecting virus infected cells or viruses themselves and make them competitive to monoclonal antibodies. Specific aptamers can be used to interfere in each stage of the viral replication cycle and also inhibit its penetration into cells. Many current studies have reported possible application of aptamers as a treatment or diagnostic tool in viral infections, e.g., HIV (Human Immunodeficiency Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus), SARS (Severe Acute Respiratory Syndrome), H5N1 avian influenza and recently spread Ebola. This review presents current developments of using aptamers in the diagnostics and treatment of viral diseases.",2015 Feb 16,"['Wandtke, Tomasz', 'Woźniak, Joanna', 'Kopiński, Piotr']",Viruses,,,True
131902a67f5e00ae13b9239427325dfd53413349,PMC,Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection,http://dx.doi.org/10.3390/v7020798,PMC4353917,25690799,CC BY,"Respiratory syncytial virus (RSV) is the leading cause of pediatric viral respiratory tract infections. Neither vaccine nor effective antiviral therapy is available to prevent and treat RSV infection. Palivizumab, a humanized monoclonal antibody, is the only product approved to prevent serious RSV infection, but its high cost is prohibitive in low-income countries. Here, we aimed to identify an effective, safe, and affordable antiviral agent for pre-exposure prophylaxis (PrEP) of RSV infection in children at high risk. We found that maleic anhydride (ML)-modified human serum albumin (HSA), designated ML-HSA, exhibited potent antiviral activity against RSV and that the percentages of the modified lysines and arginies in ML- are correlated with such anti-RSV activity. ML-HSA inhibited RSV entry and replication by interacting with viral G protein and blocking RSV attachment to the target cells, while ML-HAS neither bound to F protein, nor inhibited F protein-mediated membrane fusion. Intranasal administration of ML-HSA before RSV infection resulted in significant decrease of the viral titers in the lungs of mice. ML-HSA shows promise for further development into an effective, safe, affordable, and easy-to-use intranasal regimen for pre-exposure prophylaxis of RSV infection in children at high risk in both low- and high-income countries.",2015 Feb 16,"['Sun, Zhiwu', 'Wang, Qian', 'Jia, Ran', 'Xia, Shuai', 'Li, Yuan', 'Liu, Qi', 'Xu, Wei', 'Xu, Jin', 'Du, Lanying', 'Lu, Lu', 'Jiang, Shibo']",Viruses,,,True
92f24acca725725852dd170c673f8adac4250faa,PMC,Development of Monoclonal Antibodies in China: Overview and Prospects,http://dx.doi.org/10.1155/2015/168935,PMC4355554,25811022,CC BY,"Monoclonal antibodies (mAbs) have become increasingly important as human therapeutic agents. Yet, current research concentrates on technology itself and pays attention to developed countries. This paper aims to provide a comprehensive review of mAbs development in China through systematic analysis of drug registry, patent applications, clinical trials, academic publication, and ongoing R&D projects. The trends in therapeutic areas and industrialization process are also highlighted. Development and research trends of mAbs are analyzed to provide a future perspective of mAbs as therapeutic agents in China.",2015 Feb 25,"['Zhang, Mao-Yu', 'Lu, Jin-Jian', 'Wang, Liang', 'Gao, Zi-Chao', 'Hu, Hao', 'Ung, Carolina Oi Lam', 'Wang, Yi-Tao']",Biomed Res Int,,,True
26d93683447b88c154664f5f80b35cd7991ba106,PMC,The Anti-Porcine Parvovirus Activity of Nanometer Propolis Flavone and Propolis Flavone In Vitro and In Vivo,http://dx.doi.org/10.1155/2015/472876,PMC4357139,25815034,CC BY,"Objectives. The present study was conducted to evaluate the activity of nanometer propolis flavone (NPF) on inhibiting porcine parvovirus (PPV) in vitro and in vivo. Methods. In vitro, the effect of NPF on cellular infectivity of PPV was carried out before and after adding drug and simultaneous adding and PPV after being mixed. In vivo, the anti-PPV effect of NPF in guinea pigs was performed. Results. The results showed that NPF could significantly inhibit PPV infecting porcine kidney- (PK-) 15 cells compared with propolis flavone (PF), and the activity of NPF was the best in preadding drug pattern. NPF at high and medium doses was able to observably restrain PPV copying in lung, gonad, blood, and spleen, decrease the impact of PPV on weight of guinea pigs, and improve hemagglutination inhibition (HI) of PPV in serum. In addition, it could also increase the contents of IL-2 and IL-6 in serum after PPV challenge. Conclusion. These results indicated that NPF could significantly improve the anti-PPV activity of PF, and its high concentration possessed the best efficacy. Therefore, NPF would be expected to be exploited into a new-style antiviral drug.",2015 Feb 26,"['Ma, Xia', 'Guo, Zhenhuan', 'Shen, Zhiqiang', 'Liu, Yonglu', 'Wang, Jinliang', 'Fan, Yunpeng']",Evid Based Complement Alternat Med,,,True
b7a6a987030c52cc7ecdf49c3933b6cfda488210,PMC,A systematic review and meta-analysis of the epidemiology of pathogenic Escherichia coli of calves and the role of calves as reservoirs for human pathogenic E. coli,http://dx.doi.org/10.3389/fcimb.2015.00023,PMC4357325,25815276,CC BY,"Escherichia coli bacteria are the most common causes of diarrhea and septicemia in calves. Moreover, calves form a major reservoir for transmission of pathogenic E. coli to humans. Systematic reviews and meta-analyses of publications on E. coli as calf pathogens and the role of calves as reservoir have not been done so far. We reviewed studies between 1951 and 2013 reporting the presence of virulence associated factors (VAFs) in calf E. coli and extracted the following information: year(s) and country of sampling, animal number, health status, isolate number, VAF prevalence, serotypes, diagnostic methods, and biological assays. The prevalence of VAFs or E. coli pathotypes was compared between healthy and diarrheic animals and was analyzed for time courses. Together, 106 papers with 25,982 E. coli isolates from 27 countries tested for VAFs were included. F5, F17, and F41 fimbriae and heat-stable enterotoxin (ST) – VAFs of enterotoxigenic E. coli (ETEC) were significantly associated with calf diarrhea. On the contrary, ETEC VAF F4 fimbriae and heat-labile enterotoxin as well as enteropathogenic (EPEC), Shiga toxin-producing (STEC), and enterohemorrhagic E. coli (EHEC) were not associated with diarrhea. The prevalence increased overtime for ST-positive isolates, but decreased for F5- and STEC-positive isolates. Our study provides useful information about the history of scientific investigations performed in this domain so far, and helps to define etiological agents of calf disease, and to evaluate calves as reservoir hosts for human pathogenic E. coli.",2015 Mar 12,"['Kolenda, Rafał', 'Burdukiewicz, Michał', 'Schierack, Peter']",Front Cell Infect Microbiol,,,True
c5b4fb9b393c9e5d24b075349fbb4601ea89c8f4,PMC,Good and Bad News about Ebola,http://dx.doi.org/10.1371/journal.pntd.0003509,PMC4357473,25764305,CC BY,,2015 Mar 12,"Peterson, A. Townsend",PLoS Negl Trop Dis,,,True
9f234fa9b0d6d7c0809106111104ad8843f3a931,PMC,Monitoring Disease Trends using Hospital Traffic Data from High Resolution Satellite Imagery: A Feasibility Study,http://dx.doi.org/10.1038/srep09112,PMC4357853,25765943,CC BY,"Challenges with alternative data sources for disease surveillance include differentiating the signal from the noise, and obtaining information from data constrained settings. For the latter, events such as increases in hospital traffic could serve as early indicators of social disruption resulting from disease. In this study, we evaluate the feasibility of using hospital parking lot traffic data extracted from high-resolution satellite imagery to augment public health disease surveillance in Chile, Argentina and Mexico. We used archived satellite imagery collected from January 2010 to May 2013 and data on the incidence of respiratory virus illnesses from the Pan American Health Organization as a reference. We developed dynamical Elastic Net multivariable linear regression models to estimate the incidence of respiratory virus illnesses using hospital traffic and assessed how to minimize the effects of noise on the models. We noted that predictions based on models fitted using a sample of observations were better. The results were consistent across countries with selected models having reasonably low normalized root-mean-squared errors and high correlations for both the fits and predictions. The observations from this study suggest that if properly procured and combined with other information, this data source could be useful for monitoring disease trends.",2015 Mar 13,"['Nsoesie, Elaine O.', 'Butler, Patrick', 'Ramakrishnan, Naren', 'Mekaru, Sumiko R.', 'Brownstein, John S.']",Sci Rep,,,True
47379741a7a89589b8870290e5224096202f56fd,PMC,Monitoring Disease Trends using Hospital Traffic Data from High Resolution Satellite Imagery: A Feasibility Study,http://dx.doi.org/10.1038/srep09112,PMC4357853,25765943,CC BY,"Challenges with alternative data sources for disease surveillance include differentiating the signal from the noise, and obtaining information from data constrained settings. For the latter, events such as increases in hospital traffic could serve as early indicators of social disruption resulting from disease. In this study, we evaluate the feasibility of using hospital parking lot traffic data extracted from high-resolution satellite imagery to augment public health disease surveillance in Chile, Argentina and Mexico. We used archived satellite imagery collected from January 2010 to May 2013 and data on the incidence of respiratory virus illnesses from the Pan American Health Organization as a reference. We developed dynamical Elastic Net multivariable linear regression models to estimate the incidence of respiratory virus illnesses using hospital traffic and assessed how to minimize the effects of noise on the models. We noted that predictions based on models fitted using a sample of observations were better. The results were consistent across countries with selected models having reasonably low normalized root-mean-squared errors and high correlations for both the fits and predictions. The observations from this study suggest that if properly procured and combined with other information, this data source could be useful for monitoring disease trends.",2015 Mar 13,"['Nsoesie, Elaine O.', 'Butler, Patrick', 'Ramakrishnan, Naren', 'Mekaru, Sumiko R.', 'Brownstein, John S.']",Sci Rep,,,False
341fd3d94baafcde2e5e7c0b1d166028d69523e4,PMC,FDA approved drugs as potential Ebola treatments,http://dx.doi.org/10.12688/f1000research.6164.2,PMC4358410,25789163,CC BY,"In the search for treatments for the Ebola Virus, multiple screens of FDA drugs have led to the identification of several with promising in vitro activity. These compounds were not originally developed as antivirals and some have been further tested in mouse in vivo models. We put forward the opinion that some of these drugs could be evaluated further and move into the clinic as they are already FDA approved and in many cases readily available. This may be important if there is a further outbreak in future and no other therapeutic is available.",2015 Mar 10,"['Ekins, Sean', 'Coffee, Megan']",F1000Res,,,True
241bbd33b32abf0cc6adb68b9c80381f0856cddd,PMC,Impact of Porcine Epidemic Diarrhea on Performance of Growing Pigs,http://dx.doi.org/10.1371/journal.pone.0120532,PMC4359118,25768287,CC BY,"The impact of porcine epidemic diarrhea virus (PEDv) infection on the US pork industry has mainly been attributed to the mortality that it causes in suckling piglets, and, consequently, much effort has been invested in the quantification of its effect in sow farms. However, no information on the performance of surviving pigs that were exposed to the PEDv as piglets is available. Here, a retrospective cohort study to evaluate the impact of porcine epidemic diarrhea virus (PEDv) infection on growing pigs’ performance, as indicated by mortality, average daily gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR) was performed using production records from weaned pigs in nursery and wean-to-finish sites from sow farms that became PEDv-infected between May 2013 and June 2014. Production records from the first batch of growing pigs weaned in infected flows after the PEDv outbreak (“infected batches”) were compared with those from pigs weaned within the previous 14 to 120 days (“control batches”). Performance records from infected and control batches, paired by flow, were compared using non-parametric paired tests. Mortality, ADG and FCR were significantly different in PEDv-positive (infected) compared with PEDv-negative (control) batches, with a mean increase of mortality and FCR of 11% and 0.5, respectively, and a decrease of ADG of 0.16 lb/day. Our results demonstrate a poorer performance of growing pigs weaned after a PEDv outbreak compared with those weaned within the previous 14-120 days, suggesting that in addition to the mortality induced by PEDv in suckling pigs, the disease also impairs the performance of surviving pig. These findings help to quantify the impact of PEDv infection in the US and, ultimately, contribute to efforts to quantify the cost-effectiveness of disease prevention and control measures.",2015 Mar 13,"['Alvarez, Julio', 'Sarradell, Javier', 'Morrison, Robert', 'Perez, Andres']",PLoS One,,,True
78fb5545880b83bbbef7058bf5c99ff618b35f7b,PMC,Molecular epidemiological study of feline coronavirus strains in Japan using RT-PCR targeting nsp14 gene,http://dx.doi.org/10.1186/s12917-015-0372-2,PMC4359392,25889235,CC BY,"BACKGROUND: Feline infectious peritonitis is a fatal disease of cats caused by infection with feline coronavirus (FCoV). For detecting or genotyping of FCoV, some RT-PCR plus nested PCR techniques have been reported previously. However, referring to the whole genome sequences (WGSs) registered at NCBI, there are no detection methods that can tolerate the genetic diversity among FCoV population. In addition, the quasispecies nature of FCoV, which consists of heterogeneous variants, has been also demonstrated; thus, a universal method for heteropopulations of FCoV variants in clinical specimens is desirable. RESULTS: To develop an RT-PCR method for detection and genotyping of FCoV, we performed comparative genome analysis using WGSs of 32 FCoV, 7 CCoV and 5 TGEV strains obtained from NCBI. As the PCR target, we focused on the nsp14 coding region, which is highly conserved and phylogenetically informative, and developed a PCR method targeting nsp14 partial sequences. Among 103 ascites, 45 pleural effusion and 214 blood specimens from clinically ill cats, we could detect FCoV in 55 (53.4%), 14 (31.1%) and 19 (8.9%) specimens using the present method. Direct sequencing of PCR products and phylogenetic analysis allowed discrimination between type I- and II-FCoV serotypes. Our nsp14 amino acid sequence typing (nsp14 aa ST) showed that the FCoV clone with sequence type (ST) 42, which was the most predominant genotype of WGS strains, was prevalent in domestic cats in Japan. CONCLUSIONS: Our nsp14 PCR scheme will contribute to virus detection, epidemiology and ecology of FCoV strains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0372-2) contains supplementary material, which is available to authorized users.",2015 Mar 11,"['Tanaka, Yoshikazu', 'Sasaki, Takashi', 'Matsuda, Ryo', 'Uematsu, Yosuke', 'Yamaguchi, Tomohiro']",BMC Vet Res,,,True
1904cb0e767c673c78ac5d6ebf6260c1d83bea13,PMC,Hematopoietic Cancer Cell Lines Can Support Replication of Sabin Poliovirus Type 1,http://dx.doi.org/10.1155/2015/358462,PMC4359862,25815312,CC BY,"Viral vaccines can be produced in adherent or in suspension cells. The objective of this work was to screen human suspension cell lines for the capacity to support viral replication. As the first step, it was investigated whether poliovirus can replicate in such cell lines. Sabin poliovirus type 1 was serially passaged on five human cell lines, HL60, K562, KG1, THP-1, and U937. Sabin type 1 was capable of efficiently replicating in three cell lines (K562, KG1, and U937), yielding high viral titers after replication. Expression of CD155, the poliovirus receptor, did not explain susceptibility to replication, since all cell lines expressed CD155. Furthermore, we showed that passaged virus replicated more efficiently than parental virus in KG1 cells, yielding higher virus titers in the supernatant early after infection. Infection of cell lines at an MOI of 0.01 resulted in high viral titers in the supernatant at day 4. Infection of K562 with passaged Sabin type 1 in a bioreactor system yielded high viral titers in the supernatant. Altogether, these data suggest that K562, KG1, and U937 cell lines are useful for propagation of poliovirus.",2015 Feb 28,"['Oosterhoff, Dinja', 'van de Weerd, Gerard', 'van Eikenhorst, Gerco', 'de Gruijl, Tanja D.', 'van der Pol, Leo A.', 'Bakker, Wilfried A. M.']",Biomed Res Int,,,True
f76b1d637fdb9e5d6a32d1a6d3804a2acb9f0f23,PMC,The prevention and eradication of smallpox: a commentary on Sloane (1755) ‘An account of inoculation’,http://dx.doi.org/10.1098/rstb.2014.0378,PMC4360126,25750241,CC BY,"Sir Hans Sloane's account of inoculation as a means to protect against smallpox followed several earlier articles published in Philosophical Transactions on this procedure. Inoculation (also called ‘variolation’) involved the introduction of small amounts of infectious material from smallpox vesicles into the skin of healthy subjects, with the goal of inducing mild symptoms that would result in protection against the more severe naturally acquired disease. It began to be practised in England in 1721 thanks to the efforts of Lady Mary Wortley Montagu who influenced Sloane to promote its use, including the inoculation of the royal family's children. When Edward Jenner's inoculation with the cow pox (‘vaccination’) followed 75 years later as a safer yet equally effective procedure, the scene was set for the eventual control of smallpox epidemics culminating in the worldwide eradication of smallpox in 1977, officially proclaimed by WHO in 1980. Here, we discuss the significance of variolation and vaccination with respect to scientific, public health and ethical controversies concerning these ‘weapons of mass protection’. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.",2015 Apr 19,"['Weiss, Robin A.', 'Esparza, José']",Philos Trans R Soc Lond B Biol Sci,,,True
d469f2e82c820caea8ab2d4f92b7a5a93a23f569,PMC,"Risk Factors for Death from Influenza A(H1N1)pdm09, State of São Paulo, Brazil, 2009",http://dx.doi.org/10.1371/journal.pone.0118772,PMC4361171,25774804,CC BY,"This case-control study aimed to assess the risk factors for death from influenza A(H1N1)pdm09 in patients with laboratory confirmation, who had severe acute respiratory illness-SARI and were hospitalized between June 28(th) and August 29(th) 2009, in the metropolitan regions of São Paulo and Campinas, Brazil. Medical charts of all the 193 patients who died (cases) and the 386 randomly selected patients who recovered (controls) were investigated in 177 hospitals. Household interviews were conducted with those who had survived and the closest relative of those who had died. 73.6% of cases and 38.1% of controls were at risk of developing influenza-related complications. The 18-to-59-year age group (OR = 2.31, 95%CI: 1.31–4.10 (reference up to 18 years of age)), presence of risk conditions for severity of influenza (OR = 1.99, 95%CI: 1.11–3.57, if one or OR = 6.05, 95%CI: 2.76–13.28, if more than one), obesity (OR = 2.73, 95%CI: 1.28–5.83), immunosuppression (OR = 3.43, 95%CI: 1.28–9.19), and search for previous care associated with the hospitalization (OR = 3.35, 95%CI: 1.75–6.40) were risk factors for death. Antiviral treatment performed within 72 hours of the onset of symptoms (OR = 0.17, 95%CI: 0.08–0.37, if within 48hours, and OR = 0.30, 95%CI: 0.11–0.81, if between 48 and 72 hours) was protective against death. The identification of high-risk patients and early treatment are important factors for reducing morbi-mortality from influenza.",2015 Mar 16,"['Ribeiro, Ana Freitas', 'Pellini, Alessandra Cristina Guedes', 'Kitagawa, Beatriz Yuko', 'Marques, Daniel', 'Madalosso, Geraldine', 'de Cassia Nogueira Figueira, Gerrita', 'Fred, João', 'Albernaz, Ricardo Kerti Mangabeira', 'Carvalhanas, Telma Regina Marques Pinto', 'Zanetta, Dirce Maria Trevisan']",PLoS One,,,True
364b968c148ee72c7336bf89c06974a646683fd3,PMC,Xenosurveillance: A Novel Mosquito-Based Approach for Examining the Human-Pathogen Landscape,http://dx.doi.org/10.1371/journal.pntd.0003628,PMC4361501,25775236,CC0,"BACKGROUND: Globally, regions at the highest risk for emerging infectious diseases are often the ones with the fewest resources. As a result, implementing sustainable infectious disease surveillance systems in these regions is challenging. The cost of these programs and difficulties associated with collecting, storing and transporting relevant samples have hindered them in the regions where they are most needed. Therefore, we tested the sensitivity and feasibility of a novel surveillance technique called xenosurveillance. This approach utilizes the host feeding preferences and behaviors of Anopheles gambiae, which are highly anthropophilic and rest indoors after feeding, to sample viruses in human beings. We hypothesized that mosquito bloodmeals could be used to detect vertebrate viral pathogens within realistic field collection timeframes and clinically relevant concentrations. METHODOLOGY/PRINCIPAL FINDINGS: To validate this approach, we examined variables influencing virus detection such as the duration between mosquito blood feeding and mosquito processing, the pathogen nucleic acid stability in the mosquito gut and the pathogen load present in the host’s blood at the time of bloodmeal ingestion using our laboratory model. Our findings revealed that viral nucleic acids, at clinically relevant concentrations, could be detected from engorged mosquitoes for up to 24 hours post feeding by qRT-PCR. Subsequently, we tested this approach in the field by examining blood from engorged mosquitoes from two field sites in Liberia. Using next-generation sequencing and PCR we were able to detect the genetic signatures of multiple viral pathogens including Epstein-Barr virus and canine distemper virus. CONCLUSIONS/SIGNIFICANCE: Together, these data demonstrate the feasibility of xenosurveillance and in doing so validated a simple and non-invasive surveillance tool that could be used to complement current biosurveillance efforts.",2015 Mar 16,"['Grubaugh, Nathan D.', 'Sharma, Supriya', 'Krajacich, Benjamin J.', 'Fakoli III, Lawrence S.', 'Bolay, Fatorma K.', 'Diclaro II, Joe W.', 'Johnson, W. Evan', 'Ebel, Gregory D.', 'Foy, Brian D.', 'Brackney, Doug E.']",PLoS Negl Trop Dis,,,True
6ce5b9aac3338153eaf845252d28c3f06a0fb014,PMC,Adenovirus and Herpesvirus Diversity in Free-Ranging Great Apes in the Sangha Region of the Republic of Congo,http://dx.doi.org/10.1371/journal.pone.0118543,PMC4362762,25781992,CC BY,"Infectious diseases have caused die-offs in both free-ranging gorillas and chimpanzees. Understanding pathogen diversity and disease ecology is therefore critical for conserving these endangered animals. To determine viral diversity in free-ranging, non-habituated gorillas and chimpanzees in the Republic of Congo, genetic testing was performed on great-ape fecal samples collected near Odzala-Kokoua National Park. Samples were analyzed to determine ape species, identify individuals in the population, and to test for the presence of herpesviruses, adenoviruses, poxviruses, bocaviruses, flaviviruses, paramyxoviruses, coronaviruses, filoviruses, and simian immunodeficiency virus (SIV). We identified 19 DNA viruses representing two viral families, Herpesviridae and Adenoviridae, of which three herpesviruses had not been previously described. Co-detections of multiple herpesviruses and/or adenoviruses were present in both gorillas and chimpanzees. Cytomegalovirus (CMV) and lymphocryptovirus (LCV) were found primarily in the context of co-association with each other and adenoviruses. Using viral discovery curves for herpesviruses and adenoviruses, the total viral richness in the sample population of gorillas and chimpanzees was estimated to be a minimum of 23 viruses, corresponding to a detection rate of 83%. These findings represent the first description of DNA viral diversity in feces from free-ranging gorillas and chimpanzees in or near the Odzala-Kokoua National Park and form a basis for understanding the types of viruses circulating among great apes in this region.",2015 Mar 17,"['Seimon, Tracie A.', 'Olson, Sarah H.', 'Lee, Kerry Jo', 'Rosen, Gail', 'Ondzie, Alain', 'Cameron, Kenneth', 'Reed, Patricia', 'Anthony, Simon J.', 'Joly, Damien O.', 'McAloose, Denise', 'Lipkin, W. Ian']",PLoS One,,,True
cf8e39bf81b1e6e273adf55fb5db2245bd8bc885,PMC,The Porcine MicroRNA Transcriptome Response to Transmissible Gastroenteritis Virus Infection,http://dx.doi.org/10.1371/journal.pone.0120377,PMC4363316,25781021,CC BY,"Transmissible gastroenteritis virus (TGEV; Coronaviridae family) causes huge economic losses to the swine industry. MicroRNAs (miRNAs) play a regulatory role in viral infection and may be involved in the mammalian immune response. Here, we report a comprehensive analysis of host miRNA expression in TGEV-infected swine testis (ST) cells. Deep sequencing generated 3,704,353 and 2,763,665 reads from uninfected ST cells and infected ST cells, respectively. The reads were aligned to known Sus scrofa pre-miRNAs in miRBase 19, identifying 284 annotated miRNAs. Certain miRNAs were differentially regulated during TGEV infection. 59 unique miRNAs displayed significant differentially expression between the normal and TGEV-infected ST cell samples: 15 miRNAs were significantly up-regulated and 44 were significantly down-regulated. Stem-loop RT-PCR was carried out to determine the expression levels of specific miRNAs in the two samples, and the results were consistent with those of sequencing. Gene ontology enrichment analysis of host target genes demonstrated that the differentially expressed miRNAs are involved in regulatory networks, including cellular process, metabolic process, immune system process. This is the first report of the identification of ST cell miRNAs and the comprehensive analysis of the miRNA regulatory mechanism during TGEV infection, which revealed the miRNA molecular regulatory mechanisms for the viral infection, expression of viral genes and the expression of immune-related genes. The results presented here will aid research on the prevention and treatment of viral diseases.",2015 Mar 17,"['Liu, Xiao', 'Zhu, Ling', 'Liao, Shan', 'Xu, Zhiwen', 'Zhou, Yuancheng']",PLoS One,,,True
97d1af515c43a768c3b46d22e69a2bcddd764ceb,PMC,The Porcine MicroRNA Transcriptome Response to Transmissible Gastroenteritis Virus Infection,http://dx.doi.org/10.1371/journal.pone.0120377,PMC4363316,25781021,CC BY,"Transmissible gastroenteritis virus (TGEV; Coronaviridae family) causes huge economic losses to the swine industry. MicroRNAs (miRNAs) play a regulatory role in viral infection and may be involved in the mammalian immune response. Here, we report a comprehensive analysis of host miRNA expression in TGEV-infected swine testis (ST) cells. Deep sequencing generated 3,704,353 and 2,763,665 reads from uninfected ST cells and infected ST cells, respectively. The reads were aligned to known Sus scrofa pre-miRNAs in miRBase 19, identifying 284 annotated miRNAs. Certain miRNAs were differentially regulated during TGEV infection. 59 unique miRNAs displayed significant differentially expression between the normal and TGEV-infected ST cell samples: 15 miRNAs were significantly up-regulated and 44 were significantly down-regulated. Stem-loop RT-PCR was carried out to determine the expression levels of specific miRNAs in the two samples, and the results were consistent with those of sequencing. Gene ontology enrichment analysis of host target genes demonstrated that the differentially expressed miRNAs are involved in regulatory networks, including cellular process, metabolic process, immune system process. This is the first report of the identification of ST cell miRNAs and the comprehensive analysis of the miRNA regulatory mechanism during TGEV infection, which revealed the miRNA molecular regulatory mechanisms for the viral infection, expression of viral genes and the expression of immune-related genes. The results presented here will aid research on the prevention and treatment of viral diseases.",2015 Mar 17,"['Liu, Xiao', 'Zhu, Ling', 'Liao, Shan', 'Xu, Zhiwen', 'Zhou, Yuancheng']",PLoS One,,,False
059c5688c0caf75bf1d1532a7d36230247599064,PMC,The Porcine MicroRNA Transcriptome Response to Transmissible Gastroenteritis Virus Infection,http://dx.doi.org/10.1371/journal.pone.0120377,PMC4363316,25781021,CC BY,"Transmissible gastroenteritis virus (TGEV; Coronaviridae family) causes huge economic losses to the swine industry. MicroRNAs (miRNAs) play a regulatory role in viral infection and may be involved in the mammalian immune response. Here, we report a comprehensive analysis of host miRNA expression in TGEV-infected swine testis (ST) cells. Deep sequencing generated 3,704,353 and 2,763,665 reads from uninfected ST cells and infected ST cells, respectively. The reads were aligned to known Sus scrofa pre-miRNAs in miRBase 19, identifying 284 annotated miRNAs. Certain miRNAs were differentially regulated during TGEV infection. 59 unique miRNAs displayed significant differentially expression between the normal and TGEV-infected ST cell samples: 15 miRNAs were significantly up-regulated and 44 were significantly down-regulated. Stem-loop RT-PCR was carried out to determine the expression levels of specific miRNAs in the two samples, and the results were consistent with those of sequencing. Gene ontology enrichment analysis of host target genes demonstrated that the differentially expressed miRNAs are involved in regulatory networks, including cellular process, metabolic process, immune system process. This is the first report of the identification of ST cell miRNAs and the comprehensive analysis of the miRNA regulatory mechanism during TGEV infection, which revealed the miRNA molecular regulatory mechanisms for the viral infection, expression of viral genes and the expression of immune-related genes. The results presented here will aid research on the prevention and treatment of viral diseases.",2015 Mar 17,"['Liu, Xiao', 'Zhu, Ling', 'Liao, Shan', 'Xu, Zhiwen', 'Zhou, Yuancheng']",PLoS One,,,False
f13019c1409c978d7d11cdbbbb4b2c16abfc1bd7,PMC,Network-based analysis of comorbidities risk during an infection: SARS and HIV case studies,http://dx.doi.org/10.1186/1471-2105-15-333,PMC4363349,25344230,CC BY,"BACKGROUND: Infections are often associated to comorbidity that increases the risk of medical conditions which can lead to further morbidity and mortality. SARS is a threat which is similar to MERS virus, but the comorbidity is the key aspect to underline their different impacts. One UK doctor says ""I’d rather have HIV than diabetes"" as life expectancy among diabetes patients is lower than that of HIV. However, HIV has a comorbidity impact on the diabetes. RESULTS: We present a quantitative framework to compare and explore comorbidity between diseases. By using neighbourhood based benchmark and topological methods, we have built comorbidity relationships network based on the OMIM and our identified significant genes. Then based on the gene expression, PPI and signalling pathways data, we investigate the comorbidity association of these 2 infective pathologies with other 7 diseases (heart failure, kidney disorder, breast cancer, neurodegenerative disorders, bone diseases, Type 1 and Type 2 diabetes). Phenotypic association is measured by calculating both the Relative Risk as the quantified measures of comorbidity tendency of two disease pairs and the ϕ-correlation to measure the robustness of the comorbidity associations. The differential gene expression profiling strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response and statistically dysregulates a large number of genes, pathways and PPIs subnetworks in different pathologies such as chronic heart failure (21 genes), breast cancer (16 genes) and bone diseases (11 genes). HIV-1 induces comorbidities relationship with many other diseases, particularly strong correlation with the neurological, cancer, metabolic and immunological diseases. Similar comorbidities risk is observed from the clinical information. Moreover, SARS and HIV infections dysregulate 4 genes (ANXA3, GNS, HIST1H1C, RASA3) and 3 genes (HBA1, TFRC, GHITM) respectively that affect the ageing process. It is notable that HIV and SARS similarly dysregulated 11 genes and 3 pathways. Only 4 significantly dysregulated genes are common between SARS-CoV and MERS-CoV, including NFKBIA that is a key regulator of immune responsiveness implicated in susceptibility to infectious and inflammatory diseases. CONCLUSIONS: Our method presents a ripe opportunity to use data-driven approaches for advancing our current knowledge on disease mechanism and predicting disease comorbidities in a quantitative way. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2105-15-333) contains supplementary material, which is available to authorized users.",2014 Oct 24,"['Moni, Mohammad Ali', 'Liò, Pietro']",BMC Bioinformatics,,,False
f83277cbba652f6ef2a9893a3d470cdf6580979d,PMC,Network-based analysis of comorbidities risk during an infection: SARS and HIV case studies,http://dx.doi.org/10.1186/1471-2105-15-333,PMC4363349,25344230,CC BY,"BACKGROUND: Infections are often associated to comorbidity that increases the risk of medical conditions which can lead to further morbidity and mortality. SARS is a threat which is similar to MERS virus, but the comorbidity is the key aspect to underline their different impacts. One UK doctor says ""I’d rather have HIV than diabetes"" as life expectancy among diabetes patients is lower than that of HIV. However, HIV has a comorbidity impact on the diabetes. RESULTS: We present a quantitative framework to compare and explore comorbidity between diseases. By using neighbourhood based benchmark and topological methods, we have built comorbidity relationships network based on the OMIM and our identified significant genes. Then based on the gene expression, PPI and signalling pathways data, we investigate the comorbidity association of these 2 infective pathologies with other 7 diseases (heart failure, kidney disorder, breast cancer, neurodegenerative disorders, bone diseases, Type 1 and Type 2 diabetes). Phenotypic association is measured by calculating both the Relative Risk as the quantified measures of comorbidity tendency of two disease pairs and the ϕ-correlation to measure the robustness of the comorbidity associations. The differential gene expression profiling strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response and statistically dysregulates a large number of genes, pathways and PPIs subnetworks in different pathologies such as chronic heart failure (21 genes), breast cancer (16 genes) and bone diseases (11 genes). HIV-1 induces comorbidities relationship with many other diseases, particularly strong correlation with the neurological, cancer, metabolic and immunological diseases. Similar comorbidities risk is observed from the clinical information. Moreover, SARS and HIV infections dysregulate 4 genes (ANXA3, GNS, HIST1H1C, RASA3) and 3 genes (HBA1, TFRC, GHITM) respectively that affect the ageing process. It is notable that HIV and SARS similarly dysregulated 11 genes and 3 pathways. Only 4 significantly dysregulated genes are common between SARS-CoV and MERS-CoV, including NFKBIA that is a key regulator of immune responsiveness implicated in susceptibility to infectious and inflammatory diseases. CONCLUSIONS: Our method presents a ripe opportunity to use data-driven approaches for advancing our current knowledge on disease mechanism and predicting disease comorbidities in a quantitative way. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2105-15-333) contains supplementary material, which is available to authorized users.",2014 Oct 24,"['Moni, Mohammad Ali', 'Liò, Pietro']",BMC Bioinformatics,,,False
092193fe026d59729062786d8f576b553e11a97d,PMC,Network-based analysis of comorbidities risk during an infection: SARS and HIV case studies,http://dx.doi.org/10.1186/1471-2105-15-333,PMC4363349,25344230,CC BY,"BACKGROUND: Infections are often associated to comorbidity that increases the risk of medical conditions which can lead to further morbidity and mortality. SARS is a threat which is similar to MERS virus, but the comorbidity is the key aspect to underline their different impacts. One UK doctor says ""I’d rather have HIV than diabetes"" as life expectancy among diabetes patients is lower than that of HIV. However, HIV has a comorbidity impact on the diabetes. RESULTS: We present a quantitative framework to compare and explore comorbidity between diseases. By using neighbourhood based benchmark and topological methods, we have built comorbidity relationships network based on the OMIM and our identified significant genes. Then based on the gene expression, PPI and signalling pathways data, we investigate the comorbidity association of these 2 infective pathologies with other 7 diseases (heart failure, kidney disorder, breast cancer, neurodegenerative disorders, bone diseases, Type 1 and Type 2 diabetes). Phenotypic association is measured by calculating both the Relative Risk as the quantified measures of comorbidity tendency of two disease pairs and the ϕ-correlation to measure the robustness of the comorbidity associations. The differential gene expression profiling strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response and statistically dysregulates a large number of genes, pathways and PPIs subnetworks in different pathologies such as chronic heart failure (21 genes), breast cancer (16 genes) and bone diseases (11 genes). HIV-1 induces comorbidities relationship with many other diseases, particularly strong correlation with the neurological, cancer, metabolic and immunological diseases. Similar comorbidities risk is observed from the clinical information. Moreover, SARS and HIV infections dysregulate 4 genes (ANXA3, GNS, HIST1H1C, RASA3) and 3 genes (HBA1, TFRC, GHITM) respectively that affect the ageing process. It is notable that HIV and SARS similarly dysregulated 11 genes and 3 pathways. Only 4 significantly dysregulated genes are common between SARS-CoV and MERS-CoV, including NFKBIA that is a key regulator of immune responsiveness implicated in susceptibility to infectious and inflammatory diseases. CONCLUSIONS: Our method presents a ripe opportunity to use data-driven approaches for advancing our current knowledge on disease mechanism and predicting disease comorbidities in a quantitative way. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2105-15-333) contains supplementary material, which is available to authorized users.",2014 Oct 24,"['Moni, Mohammad Ali', 'Liò, Pietro']",BMC Bioinformatics,,,True
963a2753dda05c4a8a3a67d725477f4b7c5aa850,PMC,A reach-out system for video microscopy analysis of ciliary motions aiding PCD diagnosis,http://dx.doi.org/10.1186/s13104-015-0999-x,PMC4363456,25869032,CC BY,"BACKGROUNDS: High-speed Video-Microscopy Analysis (HVMA) is now being used to aid diagnosis of Primary Ciliary Dyskinesia (PCD). Only a few centers however, are equipped with the available resources and equipment to perform these tests. We describe our experience in HVMA reaching-out to many more peripheral and relatively remote areas. A portable computer with HVMA software, video camera and a microscope were used. Fourteen disperse pediatric centers were reached and a total of 203 subjects were tested within a relatively short time (Clinical Trial Registration: NCT 01070914 (registered February 6, 2010). RESULTS: With an average time of 20 minutes per patient, the system enabled us to test approximately 10–15 subjects per day. A valid HVMA result was made in 148 subjects and helped in the diagnosis of PCD in many of the patients who were subsequently confirmed to have PCD by electron microscopy and/or immunofluoresence and/or genetics and/or nasal Nitric Oxide testing. The sensitivity of abnormal HVMA to accurately predict PCD was 90.2%. DISCUSSION AND CONCLUSION: This is the first report of an out-reach system to record HVMA for improved diagnosis of PCD in remote regions that are not within reach of PCD centers and experts. It provides immediate preliminary results and instantaneous feedback to the physician, patient and his/her family members in these areas. Future studies to compare this system to conventional desk top systems are warranted. TRIAL REGISTRATION: NCT 01070914 (registered February 6, 2010).",2015 Mar 8,"['Amirav, Israel', 'Mussaffi, Huda', 'Roth, Yehudah', 'Schmidts, Miriam', 'Omran, Heymut', 'Werner, Claudius', None]",BMC Res Notes,,,True
824c9c7d7d8c1ec672e85def94cee3bb471cb5a0,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,True
d834c2a0c2e05777cf880d4f546ec97b062dcc42,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
2c04da72ce976795940e38e9a90e611c0c77b31e,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
e1b6c87bdaddd991a59b81a5e26c733a969a2966,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
fe283ded17eb6226b2d32e35d404810a1ba71a56,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
c2e00330921ce0f4e7d51acfc4563f89c235fe1a,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
62f22f970324e86bd0345b6d8bda6bc3a8dcb510,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
91324428bbd7efaf1a962e1ddfd2910df88421ec,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
6e5c9a3ed6c345b60a8487db57e1113331a11749,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
bc8a110db0d7d8689a85e6ecf572e072854fa59e,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
64d06661271ec6b071977aad4a76e0703afad1f8,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
fcd4c77a9251d6bb55ac8d66f1b1a29977f9d25a,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
f3a8d18c230ff34d3bde488f8db9c82f6b11fe6b,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
bef152d3ffbf6d9d35ae91a54f1eb447e18d7543,PMC,The Relationship of CSF and Plasma Cytokine Levels in HIV Infected Patients with Neurocognitive Impairment,http://dx.doi.org/10.1155/2015/506872,PMC4363531,25821806,CC BY,"Although HAD is now rare due to HAART, the milder forms of HAND persist in HIV-infected patients. HIV-induced systemic and localized inflammation is considered to be one of the mechanisms of HAND. The levels of cytokines in CSF were associated with neurocognitive impairment in HIV infection. However, the changes of cytokines involved in cognition impairment in plasma have not been shown, and their relationships between CSF and plasma require to be addressed. We compared cytokine levels in paired CSF and plasma samples from HIV-infected individuals with or without neurocognitive impairment. Cytokine concentrations were measured by Luminex xMAP. In comparing the expression levels of cytokines in plasma and CSF, IFN-α2, IL-8, IP-10, and MCP-1 were significantly higher in CSF. Eotaxin was significantly higher in plasma, whereas G-CSF showed no difference between plasma and CSF. G-CSF (P = 0.0079), IL-8 (P = 0.0223), IP-10 (P = 0.0109), and MCP-1 (P = 0.0497) in CSF showed significant difference between HIV-CI and HIV-NC group, which may indicate their relationship to HIV associated neurocognitive impairment. In addition, G-CSF (P = 0.0191) and IP-10 (P = 0.0377) in plasma were significantly higher in HIV-CI than HIV-NC. The consistent changes of G-CSF and IP-10 in paired plasma and CSF samples might enhance their potential for predicting HAND.",2015 Mar 3,"['Yuan, Lin', 'Liu, An', 'Qiao, Luxin', 'Sheng, Bo', 'Xu, Meng', 'Li, Wei', 'Chen, Dexi']",Biomed Res Int,,,True
449a30a14d55d5eb735468fac84e2dca5bcf75e4,PMC,An evaluation of contaminated complete feed as a vehicle for porcine epidemic diarrhea virus infection of naïve pigs following consumption via natural feeding behavior: proof of concept,http://dx.doi.org/10.1186/s12917-014-0176-9,PMC4363994,25091641,CC BY,"BACKGROUND: Since its initial detection in May 2013, porcine epidemic diarrhea virus (PEDV) has spread rapidly throughout the US swine industry. Initially, contaminated feed was proposed as a risk factor for PEDV; however, data were not available to support this theory. Here we provide proof of concept of this risk by describing a novel means for recovering PEDV-contaminated complete feed material from commercial swine sites and conducting an in vivo experiment to prove its infectivity. RESULTS: For on-farm detection of PEDV RNA in feed, paint rollers were used to collect material from at-risk feed bins from 3 clinically affected breeding herds. This material was tested by PCR and determined to be positive for PEDV-RNA (Ct = 19.50-22.20 range). To test infectivity, this material was pooled (Ct = 20.65) and a Treatment group of 3-week old PEDV-naïve piglets were allowed to consume it via natural feeding behavior. For the purpose of a Positive control, piglets were allowed to ingest feed spiked with stock PEDV (Ct = 18.23) while the negative control group received PEDV-free feed. Clinical signs of PEDV infection (vomiting and diarrhea) and viral shedding were observed in both the Positive control and Treatment group’ post-consumption with virus and microscopic lesions detected in intestinal samples No evidence of infection was observed in the Negative controls. CONCLUSIONS: These data provide proof of concept that contaminated complete feed can serve as a vehicle for PEDV infection of naïve pigs using natural feeding behavior.",2014 Aug 5,"['Dee, Scott', 'Clement, Travis', 'Schelkopf, Adam', 'Nerem, Joel', 'Knudsen, David', 'Christopher-Hennings, Jane', 'Nelson, Eric']",BMC Vet Res,,,True
38f94d6ff230d6a00680940606d559f893701898,PMC,Monoclonal antibody specific to HA2 glycopeptide protects mice from H3N2 influenza virus infection,http://dx.doi.org/10.1186/s13567-015-0146-7,PMC4364502,25888728,CC BY,"Canine influenza virus (CIV) subtype H3N2 is a newly identified, highly contagious respiratory pathogen that causes cough, pneumonia and other respiratory symptoms in dogs. Data indicate that the virus is responsible for recent clinical cases of dog disease in China. However, therapeutic options for this disease are very limited. In this study, seven monoclonal antibodies (mAbs) against CIV JS/10 (an H3N2 subtype virus) were produced and characterized. Among them, mAb D7, which is specific for the HA2 glycopeptide (gp), induced the highest neutralization titers. The protection provided by mAb D7 was evaluated in BALB/c mice challenged with homologous or heterologous strains of H3N2 influenza virus, including two strains of CIV and one strain of swine influenza virus (SIV). The data show that mAb D7 protected the mice from infection with the three viral strains, especially the homologous strain, which was indicated by the recovery of body weight, reduction of viral load, and reduction of tissue damage. Moreover, the levels of IFN-γ and TNF-α in the lungs, as detected by ELISA, were reduced in the infected mice treated with the mAb D7 compared with those without mAb D7 treatment. Thus, our findings demonstrate, for the first time, that a mAb could reduce the release of IFN-γ and TNF-α associated with tissue damage by CIV infection and that the mAb might be of great therapeutic value for CIV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-015-0146-7) contains supplementary material, which is available to authorized users.",2015 Mar 19,"['Xie, Xing', 'Lin, Yan', 'Pang, Maoda', 'Zhao, Yanbing', 'Kalhoro, Dildar Hussain', 'Lu, Chengping', 'Liu, Yongjie']",Vet Res,,,True
c16c86f79a95eff0e99629650c962b25249281af,PMC,Comparative analysis of cytokine transcript profiles within mediastinal lymph node compartments of pigs after infection with porcine reproductive and respiratory syndrome genotype 1 strains differing in pathogenicity,http://dx.doi.org/10.1186/s13567-015-0161-8,PMC4364558,25889072,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) induces a weak immune response enabling it to persist in different organs of infected pigs. This has been attributed to the ability of PRRSV to influence the induction of cytokine responses. In this study, we investigated the cytokine transcriptional profiles in different compartments of the mediastinal lymph node of pigs infected with three genotype 1 PRRSV strains of differing pathogenicity: the low virulence prototype Lelystad virus (LV), and UK field strain 215–06 and the highly virulent subtype 3 SU1-Bel isolate from Belarus. We have used a combination of laser capture micro-dissection (LCM) followed by real time quantitative PCR (RT-qPCR) and immunohistochemical (IHC) detection of immune cell markers (CD3, CD79a and MAC387) and RT-qPCR quantification of PRRSV and cytokine transcripts. Compared to mock infected pigs, we found a significant downregulation of TNF-α and IFN-α in follicular and interfollicular areas of the mediastinal lymph node from 3 days post-infection (dpi) in animals infected with all three strains. This was accompanied by a transient B cell depletion and T cell and macrophage infiltration in the follicles together with T cell depletion in the interfollicular areas. A delayed upregulation of IFN-γ and IL-23p19 was observed mainly in the follicles. The PRRSV load was higher in all areas and time-points studied in the animals infected with the SU1-Bel strain. This paper describes the first application of LCM to study the cytokine transcript profiles and virus distribution in different compartments of the lymph node of pigs.",2015 Mar 19,"['García-Nicolás, Obdulio', 'Rosales, Rubén S', 'Pallarés, Francisco J', 'Risco, David', 'Quereda, Juan J', 'Graham, Simon P', 'Frossard, Jean-Pierre', 'Morgan, Sophie B', 'Steinbach, Falko', 'Drew, Trevor W', 'Strickland, Tony S', 'Salguero, Francisco J']",Vet Res,,,True
cde537507323b28a413a559c934c435b24546c63,PMC,Isolation and Identification of a Natural Reassortant Mammalian Orthoreovirus from Least Horseshoe Bat in China,http://dx.doi.org/10.1371/journal.pone.0118598,PMC4364601,25781475,CC BY,"BACKGROUND: Mammalian orthoreoviruses (MRVs) have a wide geographic distribution and can infect virtually all mammals. Infections in humans may be either symptomatic or asymptomatic. This study describes the isolation and identification of a natural reassortant MRV from least horseshoe bats (Rhinolophus pusillu) in China, referred to as RpMRV-YN2012. METHODS AND RESULTS: The RpMRV-YN2012 was obtained from urine samples of Rhinolophus pusillus by cell culture. Negative-staining electron microscopy revealed that RpMRV-YN2012 was a non-enveloped icosahedral virus with ∼75 nm in diameter. Polyacrylamide gel electrophoresis (PAGE) migration patterns of the genome segments showed that RpMRV-YN2012 contained 10 segments in a 3:3:4 arrangement. The whole genome sequence of RpMRV2012 was determined. The consensus terminal sequences of all segments of 5’-GCUAh…yUCAUC-3’ (h = A, U or C; y = C or U) were similar to the MRV species within the genus Orthoreovirus. Its evolution and evidence of genetic reassortment were analyzed by sequence comparison and phylogenetic analysis. The results showed that RpMRV-YN2012 is a novel serotype 2 MRV that may have originated from reassortment among bat, human, and/or pig MRV strains which associated with diarrhea, acute gastroenteritis and necrotizing encephalopathy in animals and humans. CONCLUSIONS: RpMRV-YN2012 is a novel bat reassortant MRV, which may have resulted from a reassortment involving MRVs known to infect humans and animals. It is necessary to identify whether RpMRV-YN2012 is associated with diarrhea, acute gastroenteritis and necrotizing encephalopathy in clinical patients. In addition, we should carefully monitor its evolution and virulence in real time.",2015 Mar 17,"['Wang, Lihua', 'Fu, Shihong', 'Cao, Lei', 'Lei, Wenwen', 'Cao, Yuxi', 'Song, Jingdong', 'Tang, Qing', 'Zhang, Hailin', 'Feng, Yun', 'Yang, Weihong', 'Liang, Guodong']",PLoS One,,,True
592c1efd20dcb1ff5644f5d20e76f2c28a2b8da0,PMC,Vaccination with Human Papillomavirus Pseudovirus-Encapsidated Plasmids Targeted to Skin Using Microneedles,http://dx.doi.org/10.1371/journal.pone.0120797,PMC4364728,25785935,CC0,"Human papilloma virus-like particles (HPV VLP) serve as the basis of the current licensed vaccines for HPV. We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from respiratory syncytial virus (RSV) in HPV pseudovirions (PsV) is immunogenic when delivered intravaginally. Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. In this study we asked: 1) whether HPV16 VLP administered by microneedles could induce protective immune responses to HPV16 and 2) whether HPV16 PsV-encapsidated plasmids delivered by microneedles could elicit immune responses to both HPV and the antigen delivered by the transgene. Mice immunized with HPV16 VLP coated microneedles generated robust neutralizing antibody responses and were protected from HPV16 challenge. Microneedle arrays coated with HPV16-M/M2 or HPV16-F protein (genes of RSV) were then tested and dose-dependent HPV and F-specific antibody responses were detected post-immunization, and M/M2-specific T-cell responses were detected post RSV challenge, respectively. HPV16 PsV-F immunized mice were fully protected from challenge with HPV16 PsV and had reduced RSV viral load in lung and nose upon intranasal RSV challenge. In summary, HPV16 PsV-encapsidated DNA delivered by microneedles induced neutralizing antibody responses against HPV and primed for antibody and T-cell responses to RSV antigens encoded by the encapsidated plasmids. Although the immunogenicity of the DNA component was just above the dose response threshold, the HPV-specific immunity was robust. Taken together, these data suggest microneedle delivery of lyophilized HPV PsV could provide a practical, thermostable combined vaccine approach that could be developed for clinical evaluation.",2015 Mar 18,"['Kines, Rhonda C.', 'Zarnitsyn, Vladimir', 'Johnson, Teresa R.', 'Pang, Yuk-Ying S.', 'Corbett, Kizzmekia S.', 'Nicewonger, John D.', 'Gangopadhyay, Anu', 'Chen, Man', 'Liu, Jie', 'Prausnitz, Mark R.', 'Schiller, John T.', 'Graham, Barney S.']",PLoS One,,,True
96ae683c7f824b0810ce750d60c15181b93181a4,PMC,Establishment of Hairy Root Cultures by Agrobacterium Rhizogenes Mediated Transformation of Isatis Tinctoria L. for the Efficient Production of Flavonoids and Evaluation of Antioxidant Activities,http://dx.doi.org/10.1371/journal.pone.0119022,PMC4364778,25785699,CC BY,"In this work, Isatis tinctoria hairy root cultures (ITHRCs) were established as an alternative source for flavonoids (FL) production. I. tinctoria hairy root line V was found to be the most efficient line and was further confirmed by the PCR amplification of rolB, rolC and aux1 genes. Culture parameters of ITHRCs were optimized by Box-Behnken design (BBD), and eight bioactive FL constituents (rutin, neohesperidin, buddleoside, liquiritigenin, quercetin, isorhamnetin, kaempferol and isoliquiritigenin) were quali-quantitatively determined by LC-MS/MS. Under optimal conditions, the total FL accumulation of ITHRCs (24 day-old) achieved was 438.10 μg/g dry weight (DW), which exhibited significant superiority as against that of 2 year-old field grown roots (341.73 μg/g DW). Additionally, in vitro antioxidant assays demonstrated that ITHRCs extracts exhibited better antioxidant activities with lower IC(50) values (0.41 and 0.39, mg/mL) as compared to those of field grown roots (0.56 and 0.48, mg/mL). To the best of our knowledge, this is the first report describing FL production and antioxidant activities from ITHRCs.",2015 Mar 18,"['Gai, Qing-Yan', 'Jiao, Jiao', 'Luo, Meng', 'Wei, Zuo-Fu', 'Zu, Yuan-Gang', 'Ma, Wei', 'Fu, Yu-Jie']",PLoS One,,,True
9a0fe7316ddd2f7cfcaa5e7500f781357477f3d1,PMC,A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections,http://dx.doi.org/10.1371/journal.pone.0120012,PMC4364938,25785720,CC BY,"Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.",2015 Mar 18,"['Oved, Kfir', 'Cohen, Asi', 'Boico, Olga', 'Navon, Roy', 'Friedman, Tom', 'Etshtein, Liat', 'Kriger, Or', 'Bamberger, Ellen', 'Fonar, Yura', 'Yacobov, Renata', 'Wolchinsky, Ron', 'Denkberg, Galit', 'Dotan, Yaniv', 'Hochberg, Amit', 'Reiter, Yoram', 'Grupper, Moti', 'Srugo, Isaac', 'Feigin, Paul', 'Gorfine, Malka', 'Chistyakov, Irina', 'Dagan, Ron', 'Klein, Adi', 'Potasman, Israel', 'Eden, Eran']",PLoS One,,,True
eb4ec643240ca1dd5d566ff1fcf0a36fa97ee7fb,PMC,A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections,http://dx.doi.org/10.1371/journal.pone.0120012,PMC4364938,25785720,CC BY,"Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.",2015 Mar 18,"['Oved, Kfir', 'Cohen, Asi', 'Boico, Olga', 'Navon, Roy', 'Friedman, Tom', 'Etshtein, Liat', 'Kriger, Or', 'Bamberger, Ellen', 'Fonar, Yura', 'Yacobov, Renata', 'Wolchinsky, Ron', 'Denkberg, Galit', 'Dotan, Yaniv', 'Hochberg, Amit', 'Reiter, Yoram', 'Grupper, Moti', 'Srugo, Isaac', 'Feigin, Paul', 'Gorfine, Malka', 'Chistyakov, Irina', 'Dagan, Ron', 'Klein, Adi', 'Potasman, Israel', 'Eden, Eran']",PLoS One,,,False
d692faf09c38fc62f237f0ff9f2b3a2751ff76f7,PMC,A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections,http://dx.doi.org/10.1371/journal.pone.0120012,PMC4364938,25785720,CC BY,"Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.",2015 Mar 18,"['Oved, Kfir', 'Cohen, Asi', 'Boico, Olga', 'Navon, Roy', 'Friedman, Tom', 'Etshtein, Liat', 'Kriger, Or', 'Bamberger, Ellen', 'Fonar, Yura', 'Yacobov, Renata', 'Wolchinsky, Ron', 'Denkberg, Galit', 'Dotan, Yaniv', 'Hochberg, Amit', 'Reiter, Yoram', 'Grupper, Moti', 'Srugo, Isaac', 'Feigin, Paul', 'Gorfine, Malka', 'Chistyakov, Irina', 'Dagan, Ron', 'Klein, Adi', 'Potasman, Israel', 'Eden, Eran']",PLoS One,,,True
9148852f390403699eb166e03dc4147520b7ed5e,PMC,A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections,http://dx.doi.org/10.1371/journal.pone.0120012,PMC4364938,25785720,CC BY,"Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.",2015 Mar 18,"['Oved, Kfir', 'Cohen, Asi', 'Boico, Olga', 'Navon, Roy', 'Friedman, Tom', 'Etshtein, Liat', 'Kriger, Or', 'Bamberger, Ellen', 'Fonar, Yura', 'Yacobov, Renata', 'Wolchinsky, Ron', 'Denkberg, Galit', 'Dotan, Yaniv', 'Hochberg, Amit', 'Reiter, Yoram', 'Grupper, Moti', 'Srugo, Isaac', 'Feigin, Paul', 'Gorfine, Malka', 'Chistyakov, Irina', 'Dagan, Ron', 'Klein, Adi', 'Potasman, Israel', 'Eden, Eran']",PLoS One,,,True
0f9aaacbdad195c0133c25eb6dc02585ba7e1e2b,PMC,A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections,http://dx.doi.org/10.1371/journal.pone.0120012,PMC4364938,25785720,CC BY,"Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.",2015 Mar 18,"['Oved, Kfir', 'Cohen, Asi', 'Boico, Olga', 'Navon, Roy', 'Friedman, Tom', 'Etshtein, Liat', 'Kriger, Or', 'Bamberger, Ellen', 'Fonar, Yura', 'Yacobov, Renata', 'Wolchinsky, Ron', 'Denkberg, Galit', 'Dotan, Yaniv', 'Hochberg, Amit', 'Reiter, Yoram', 'Grupper, Moti', 'Srugo, Isaac', 'Feigin, Paul', 'Gorfine, Malka', 'Chistyakov, Irina', 'Dagan, Ron', 'Klein, Adi', 'Potasman, Israel', 'Eden, Eran']",PLoS One,,,True
50c5334ead9ce88189c0840243fb64fa9599bfdb,PMC,A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections,http://dx.doi.org/10.1371/journal.pone.0120012,PMC4364938,25785720,CC BY,"Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.",2015 Mar 18,"['Oved, Kfir', 'Cohen, Asi', 'Boico, Olga', 'Navon, Roy', 'Friedman, Tom', 'Etshtein, Liat', 'Kriger, Or', 'Bamberger, Ellen', 'Fonar, Yura', 'Yacobov, Renata', 'Wolchinsky, Ron', 'Denkberg, Galit', 'Dotan, Yaniv', 'Hochberg, Amit', 'Reiter, Yoram', 'Grupper, Moti', 'Srugo, Isaac', 'Feigin, Paul', 'Gorfine, Malka', 'Chistyakov, Irina', 'Dagan, Ron', 'Klein, Adi', 'Potasman, Israel', 'Eden, Eran']",PLoS One,,,True
dd5f8cf7e557b09094248fd8fbc59fbf7f01649e,PMC,A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections,http://dx.doi.org/10.1371/journal.pone.0120012,PMC4364938,25785720,CC BY,"Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.",2015 Mar 18,"['Oved, Kfir', 'Cohen, Asi', 'Boico, Olga', 'Navon, Roy', 'Friedman, Tom', 'Etshtein, Liat', 'Kriger, Or', 'Bamberger, Ellen', 'Fonar, Yura', 'Yacobov, Renata', 'Wolchinsky, Ron', 'Denkberg, Galit', 'Dotan, Yaniv', 'Hochberg, Amit', 'Reiter, Yoram', 'Grupper, Moti', 'Srugo, Isaac', 'Feigin, Paul', 'Gorfine, Malka', 'Chistyakov, Irina', 'Dagan, Ron', 'Klein, Adi', 'Potasman, Israel', 'Eden, Eran']",PLoS One,,,True
45c54d1883027b09c51ea00cb13b1980569592a6,PMC,Viral aetiology of acute respiratory infections among children and associated meteorological factors in southern China,http://dx.doi.org/10.1186/s12879-015-0863-6,PMC4365542,25884513,CC BY,"BACKGROUND: Acute respiratory infections (ARIs) are common in children and mostly caused by viruses, but the significance of the detection of multiple viruses in ARIs is unclear. This study investigated 14 respiratory viruses in ARIs among children and associated meteorological factors in Shantou, southern China. METHODS: Paired nasal/throat-flocked swabs collected from 1,074 children with ARIs, who visited outpatient walk-in clinics in a tertiary hospital between December 2010 and November 2011, were examined for fourteen respiratory viruses - influenza viruses (FluA, FluB), respiratory syncytial viruses (RSV A and B), human coronaviruses (hCoV: 229E, OC43, HKU1, NL63), human metapneumoviruses (hMPV A and B), parainfluenza viruses (PIV1-4), human rhinoviruses (HRV A, B, C), enteroviruses (EV), adenoviruses (ADV), human bocavirus (hBoV), and human parechoviruses (hPeV) - by multiplex real-time PCR. RESULTS: We identified at least one virus in 82.3% (884/1,074) and multiple viruses in 38.6% (415/1,074) of patients. EV and HRV were the most frequently detected single viruses (42.3%, 374/884 and 39.9%, 353/884 respectively) and co-detected pair (23.1%, 96/415). Overlapping seasonal trends of viruses were recorded over the year, with dual peaks for EV and single peaks for the others. By logistic regression analysis, EV was positively associated with the average temperature and humidity, hCoV, and PIV4, but negatively with HRV, PIV3, and hBoV. HRV was inversely associated with EV and PIV3. CONCLUSIONS: This study reports high viral detection and co-detection rates in pediatric ARI cases mainly due to EV and HRV. Many viruses circulated throughout the year with similar seasonal trends in association with temperature, humidity, and wind velocity. Statistically significant associations were present among the viruses. Understanding the polyviral etiology and viral interactions in the cases with multiple viruses warrants further studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0863-6) contains supplementary material, which is available to authorized users.",2015 Mar 13,"['Cui, Binglin', 'Zhang, Dangui', 'Pan, Hui', 'Zhang, Fan', 'Farrar, Jeremy', 'Law, Frieda', 'van Doorn, H Rogier', 'Wu, Beiyan', 'Ba-Thein, William']",BMC Infect Dis,,,True
c98b61b984da63b53eeef9f81e31a5ee79396b1d,PMC,Bovine Rhinitis Viruses Are Common in U.S. Cattle with Bovine Respiratory Disease,http://dx.doi.org/10.1371/journal.pone.0121998,PMC4366061,25789939,CC BY,"Bovine rhinitis viruses (BRV) are established etiological agents of bovine respiratory disease complex however little research into their epidemiology and ecology has been published for several decades. In the U.S., only bovine rhinitis A virus 1 (BRAV1) has been identified while bovine rhinitis A virus 2 (BRAV2) and bovine rhinitis B virus (BRBV) were previously only identified in England and Japan, respectively. Metagenomic sequencing of a nasal swab from a bovine respiratory disease (BRD) diagnostic submission from Kansas identified contigs with approximately 90% nucleotide similarity to BRAV2 and BRBV. A combination of de novo and templated assemblies using reference genomes yielded near complete BRAV2 and BRBV genomes. The near complete genome of bovine rhinitis A virus 1 (BRAV1) was also determined from a historical isolate to enable further molecular epidemiological studies. A 5’-nuclease reverse transcription PCR assay targeting the 3D polymerase gene was designed and used to screen 204 archived BRD clinical specimens. Thirteen (6.4%) were positive. Metagenomic sequencing of six positive samples identified mixed BRAV1/BRAV2, BRAV1/BRBV and BRAV2/BRBV infections for five samples. One sample showed infection only with BRAV1. Seroprevalence studies using a cell culture adapted BRBV found immunofluorescence assay-reactive antibodies were common in the herds analyzed. Altogether, these results demonstrate that BRV infections are common in cattle with respiratory disease and that BRAV1, BRAV2 and BRBV co-circulate in U.S. cattle and have high similarity to viruses isolated more than 30 years ago from diverse locations.",2015 Mar 19,"['Hause, Ben M.', 'Collin, Emily A.', 'Anderson, Joe', 'Hesse, Richard A.', 'Anderson, Gary']",PLoS One,,,True
7d2bd0d04e9e4418d308e40557a3c397eaada71d,PMC,"Molecular Characterization and Phylogenetic Analysis of Porcine Epidemic Diarrhea Viruses Associated with Outbreaks of Severe Diarrhea in Piglets in Jiangxi, China 2013",http://dx.doi.org/10.1371/journal.pone.0120310,PMC4366183,25790462,CC BY,"Porcine epidemic diarrhea (PED), caused by porcine epidemic diarrhea virus (PEDV), is a highly contagious, acute enteric viral disease of swine characterized by vomiting, watery diarrhea, dehydration and death. To identify and characterize the field PEDVs associated with the outbreaks of severe diarrhea in piglets in Jiangxi, 2013, the complete genome sequences of two representative strains of PEDV, designated CH/JX-1/2013 and CH/JX-2/2013, were determined and analyzed. The genome sequences of both emergent Jiangxi PEDV strains, CH/JX-1/2013 and CH/JX-2/2013, were 28,038 nucleotides in length excluding 3’ poly (A) tail. Compared to the PEDV CV777 strain, CH/JX-1/2013 and CH/JX-2/2013 had some unique genetic characteristics in the proximal region of the 5´-UTRs. Phylogenetic analysis of the complete genomes and the structural proteins revealed that CH/JX-1/2013 and CH/JX-2/2013 had a close relationship with post-2010 Chinese PEDV strains and US strains identified in 2013. The nucleotide identity between the two Jiangxi strains (CH/JX-1/2013 and CH/JX-2/2013) and 30 strains of PEDV identified ante-2010 and post-2010 ranged from 96.3–97.0% and 97.3–99.7%, respectively. Multiple nucleotide and deduced amino acid mutations were observed in the ORF1a/b, S, ORF3, E, M and N genes among the current field PEDV strains when compared to the CV777 strain. Some of the mutations altered the amino acid charge and hydrophilicity, and notably, there was an amino acid substitution in the middle of one neutralizing epitope (L1371I) of the S gene of both CH/JX-1/2013 and CH/JX-2/2013. Taken together, the accumulated genetic variations of the current field PEDV strains might have led to antigenic changes of the viruses, which might confer the less effectiveness or failure of the CV777-based vaccines currently being widely used in Jiangxi, China.",2015 Mar 19,"['Song, Deping', 'Huang, Dongyan', 'Peng, Qi', 'Huang, Tao', 'Chen, Yanjun', 'Zhang, Tiansheng', 'Nie, Xiaowei', 'He, Houjun', 'Wang, Ping', 'Liu, Qinglan', 'Tang, Yuxin']",PLoS One,,,True
4d44402d0831ef5a86694ff70f9764a46fa06deb,PMC,Sublingual Immunization of Trivalent Human Papillomavirus DNA Vaccine in Baculovirus Nanovector for Protection against Vaginal Challenge,http://dx.doi.org/10.1371/journal.pone.0119408,PMC4366369,25789464,CC BY,"Here, we report the immunogenicity of a sublingually delivered, trivalent human papillomavirus (HPV) DNA vaccine encapsidated in a human endogenous retrovirus (HERV) envelope-coated, nonreplicable, baculovirus nanovector. The HERV envelope-coated, nonreplicable, baculovirus-based DNA vaccine, encoding HPV16L1, -18L1 and -58L1 (AcHERV-triHPV), was constructed and sublingually administered to mice without adjuvant. Following sublingual (SL) administration, AcHERV-triHPV was absorbed and distributed throughout the body. At 15 minutes and 1 day post-dose, the distribution of AcHERV-triHPV to the lung was higher than that to other tissues. At 30 days post-dose, the levels of AcHERV-triHPV had diminished throughout the body. Six weeks after the first of three doses, 1×10(8) copies of SL AcHERV-triHPV induced HPV type-specific serum IgG and neutralizing antibodies to a degree comparable to that of IM immunization with 1×10(9) copies. AcHERV-triHPV induced HPV type-specific vaginal IgA titers in a dose-dependent manner. SL immunization with 1×10(10) copies of AcHERV-triHPV induced Th1 and Th2 cellular responses comparable to IM immunization with 1×10(9) copies. Molecular imaging revealed that SL AcHERV-triHPV in mice provided complete protection against vaginal challenge with HPV16, HPV18, and HPV58 pseudoviruses. These results support the potential of SL immunization using multivalent DNA vaccine in baculovirus nanovector for induction of mucosal, systemic, and cellular immune responses.",2015 Mar 19,"['Lee, Hee-Jung', 'Cho, Hansam', 'Kim, Mi-Gyeong', 'Heo, Yoon-Ki', 'Cho, Yeondong', 'Gwon, Yong-Dae', 'Park, Ki Hoon', 'Jin, Hyerim', 'Kim, Jinyoung', 'Oh, Yu-Kyoung', 'Kim, Young Bong']",PLoS One,,,True
f3025ff285a3ab111229e38adaa5edb38406d3e1,PMC,The Impact of Prior Information on Estimates of Disease Transmissibility Using Bayesian Tools,http://dx.doi.org/10.1371/journal.pone.0118762,PMC4368801,25793993,CC BY,"The basic reproductive number (R₀) and the distribution of the serial interval (SI) are often used to quantify transmission during an infectious disease outbreak. In this paper, we present estimates of R₀ and SI from the 2003 SARS outbreak in Hong Kong and Singapore, and the 2009 pandemic influenza A(H1N1) outbreak in South Africa using methods that expand upon an existing Bayesian framework. This expanded framework allows for the incorporation of additional information, such as contact tracing or household data, through prior distributions. The results for the R₀ and the SI from the influenza outbreak in South Africa were similar regardless of the prior information ([Image: see text] = 1.36–1.46, [Image: see text] = 2.0–2.7, [Image: see text] = mean of the SI). The estimates of R₀ and μ for the SARS outbreak ranged from 2.0–4.4 and 7.4–11.3, respectively, and were shown to vary depending on the use of contact tracing data. The impact of the contact tracing data was likely due to the small number of SARS cases relative to the size of the contact tracing sample.",2015 Mar 20,"['Moser, Carlee B.', 'Gupta, Mayetri', 'Archer, Brett N.', 'White, Laura F.']",PLoS One,,,True
e64a2ab805fe19fae40eb382eccb7ea82a997a1d,PMC,Proteomic Analysis of Urine Exosomes Reveals Renal Tubule Response to Leptospiral Colonization in Experimentally Infected Rats,http://dx.doi.org/10.1371/journal.pntd.0003640,PMC4368819,25793258,CC BY,"BACKGROUND: Infectious Leptospira colonize the kidneys of reservoir (e.g. rats) and accidental hosts such as humans. The renal response to persistent leptospiral colonization, as measured by urinary protein biosignatures, has not been systematically studied. Urinary exosomes--bioactive membrane-bound nanovesicles--contain cell-state specific cargo that additively reflect formation all along the nephron. We hypothesized that Leptospira-infection will alter the content of urine exosomes, and further, that these Leptospira-induced alterations will hold clues to unravel novel pathways related to bacterial-host interactions. METHODOLOGY/PRINCIPAL FINDINGS: Exosome protein content from 24 hour urine samples of Leptospira-infected rats was compared with that of uninfected rats using SDS-PAGE and liquid chromatography/tandem mass spectrometry (LC-MS/MS). Statistical models were used to identify significantly dysregulated proteins in Leptospira-infected and uninfected rat urine exosomes. In all, 842 proteins were identified by LC-MS/MS proteomics of total rat urine and 204 proteins associated specifically with exosomes. Multivariate analysis showed that 25 proteins significantly discriminated between uninfected control and infected rats. Alanyl (membrane) aminopeptidase, also known as CD13 topped this list with the highest score, a finding we validated by Western immunoblotting. Whole urine analysis showed Tamm-Horsfall protein level reduction in the infected rat urine. Total urine and exosome proteins were significantly different in male vs. female infected rats. CONCLUSIONS: We identified exosome-associated renal tubule-specific responses to Leptospira infection in a rat chronic colonization model. Quantitative differences in infected male and female rat urine exosome proteins vs. uninfected controls suggest that urine exosome analysis identifies important differences in kidney function that may be of clinical and pathological significance.",2015 Mar 20,"['RamachandraRao, Satish P.', 'Matthias, Michael A.', 'Mondrogon, Chanthel-Kokoy', 'Aghania, Eamon', 'Park, Cathleen', 'Kong, Casey', 'Ishaya, Michelle', 'Madrigal, Assael', 'Horng, Jennifer', 'Khoshaba, Roni', 'Bounkhoun, Anousone', 'Basilico, Fabrizio', 'De Palma, Antonella', 'Agresta, Anna Maria', 'Awdishu, Linda', 'Naviaux, Robert K.', 'Vinetz, Joseph M.', 'Mauri, Pierluigi']",PLoS Negl Trop Dis,,,True
51b8bdc5f732c68e830a09eb2ecd73191e6df2dd,PMC,Bats and zoonotic viruses: can we confidently link bats with emerging deadly viruses?,http://dx.doi.org/10.1590/0074-02760150048,PMC4371215,25742261,CC BY,"An increasingly asked question is 'can we confidently link bats with emerging viruses?'. No, or not yet, is the qualified answer based on the evidence available. Although more than 200 viruses - some of them deadly zoonotic viruses - have been isolated from or otherwise detected in bats, the supposed connections between bats, bat viruses and human diseases have been raised more on speculation than on evidence supporting their direct or indirect roles in the epidemiology of diseases (except for rabies). However, we are convinced that the evidence points in that direction and that at some point it will be proved that bats are competent hosts for at least a few zoonotic viruses. In this review, we cover aspects of bat biology, ecology and evolution that might be relevant in medical investigations and we provide a historical synthesis of some disease outbreaks causally linked to bats. We provide evolutionary-based hypotheses to tentatively explain the viral transmission route through mammalian intermediate hosts and to explain the geographic concentration of most outbreaks, but both are no more than speculations that still require formal assessment.",2015 Feb,"['Moratelli, Ricardo', 'Calisher, Charles H']",Mem Inst Oswaldo Cruz,,,True
34b2b1fe3361c684f52c9a60f48f579edb8f52dc,PMC,"Effect of Puumala hantavirus infection on human umbilical vein endothelial cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release",http://dx.doi.org/10.3389/fmicb.2015.00220,PMC4371750,25852676,CC BY,"Puumala virus (PUUV) infection causes over 5000 cases of hemorrhagic fever in Europe annually and can influence the hemostatic balance extensively. Infection might lead to hemorrhage, while a recent study showed an increased risk of myocardial infarction during or shortly after PUUV infection. The mechanism by which this hantavirus influences the coagulation system remains unknown. Therefore we aimed to elucidate mechanisms explaining alterations seen in primary and secondary hemostasis during PUUV infection. By using low passage PUUV isolates to infect primary human umbilical vein endothelial cells (HUVECs) we were able to show alterations in the regulation of primary- and secondary hemostasis and in the release of fibrinolysis regulators. Our main finding was an activation of secondary hemostasis due to increased tissue factor (TF) expression leading to increased thrombin generation in a functional assay. Furthermore, we showed that during infection platelets adhered to HUVEC and subsequently specifically to PUUV virus particles. Infection of HUVEC with PUUV did not result in increased von Willebrand factor while they produced more plasminogen activator inhibitor type-1 (PAI-1) compared to controls. The PAI-1 produced in this model formed complexes with vitronectin. This is the first report that reveals a potential mechanism behind the pro-coagulant changes in PUUV patients, which could be the result of increased thrombin generation due to an increased TF expression on endothelial cells during infection. Furthermore, we provide insight into the contribution of endothelial cell responses regarding hemostasis in PUUV pathogenesis.",2015 Mar 24,"['Goeijenbier, Marco', 'Meijers, Joost C. M.', 'Anfasa, Fatih', 'Roose, Jeroen M.', 'van de Weg, Cornelia A. M.', 'Bakhtiari, Kamran', 'Henttonen, Heikki', 'Vaheri, Antti', 'Osterhaus, Albert D. M. E.', 'van Gorp, Eric C. M.', 'Martina, Byron E. E.']",Front Microbiol,,,True
715ec0aac4ad78092007345159945afa560b3f05,PMC,Strengthening the Detection of and Early Response to Public Health Emergencies: Lessons from the West African Ebola Epidemic,http://dx.doi.org/10.1371/journal.pmed.1001804,PMC4371887,25803303,CC BY,Mark Siedner and colleagues reflect on the early response to the Ebola epidemic and lessons that can be learned for future epidemics.,2015 Mar 24,"['Siedner, Mark J.', 'Gostin, Lawrence O.', 'Cranmer, Hilarie H.', 'Kraemer, John D.']",PLoS Med,,,True
fff3678cfe3ce7a9ccae1e7becf17d5d71d1b54a,PMC,Gaining Insights into the Codon Usage Patterns of TP53 Gene across Eight Mammalian Species,http://dx.doi.org/10.1371/journal.pone.0121709,PMC4373688,25807269,CC BY,"TP53 gene is known as the “guardian of the genome” as it plays a vital role in regulating cell cycle, cell proliferation, DNA damage repair, initiation of programmed cell death and suppressing tumor growth. Non uniform usage of synonymous codons for a specific amino acid during translation of protein known as codon usage bias (CUB) is a unique property of the genome and shows species specific deviation. Analysis of codon usage bias with compositional dynamics of coding sequences has contributed to the better understanding of the molecular mechanism and the evolution of a particular gene. In this study, the complete nucleotide coding sequences of TP53 gene from eight different mammalian species were used for CUB analysis. Our results showed that the codon usage patterns in TP53 gene across different mammalian species has been influenced by GC bias particularly GC(3) and a moderate bias exists in the codon usage of TP53 gene. Moreover, we observed that nature has highly favored the most over represented codon CTG for leucine amino acid but selected against the ATA codon for isoleucine in TP53 gene across all mammalian species during the course of evolution.",2015 Mar 25,"['Mazumder, Tarikul Huda', 'Chakraborty, Supriyo']",PLoS One,,,True
b70653608d4d8838aaf1dae4e710fa03a858df43,PMC,The Highly Conserved Codon following the Slippery Sequence Supports −1 Frameshift Efficiency at the HIV-1 Frameshift Site,http://dx.doi.org/10.1371/journal.pone.0122176,PMC4373837,25807539,CC BY,"HIV-1 utilises −1 programmed ribosomal frameshifting to translate structural and enzymatic domains in a defined proportion required for replication. A slippery sequence, U UUU UUA, and a stem-loop are well-defined RNA features modulating −1 frameshifting in HIV-1. The GGG glycine codon immediately following the slippery sequence (the ‘intercodon’) contributes structurally to the start of the stem-loop but has no defined role in current models of the frameshift mechanism, as slippage is inferred to occur before the intercodon has reached the ribosomal decoding site. This GGG codon is highly conserved in natural isolates of HIV. When the natural intercodon was replaced with a stop codon two different decoding molecules—eRF1 protein or a cognate suppressor tRNA—were able to access and decode the intercodon prior to −1 frameshifting. This implies significant slippage occurs when the intercodon is in the (perhaps distorted) ribosomal A site. We accommodate the influence of the intercodon in a model of frame maintenance versus frameshifting in HIV-1.",2015 Mar 25,"['Mathew, Suneeth F.', 'Crowe-McAuliffe, Caillan', 'Graves, Ryan', 'Cardno, Tony S.', 'McKinney, Cushla', 'Poole, Elizabeth S.', 'Tate, Warren P.']",PLoS One,,,True
9413ac12d29207f16ff2983940960e00f296ec15,PMC,Virocidal activity of Egyptian scorpion venoms against hepatitis C virus,http://dx.doi.org/10.1186/s12985-015-0276-6,PMC4374190,25889296,CC BY,"BACKGROUND: Hepatitis C virus (HCV) is a major global health problem, causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Development of well-tolerated regimens with high cure rates and fewer side effects is still much needed. Recently, natural antimicrobial peptides (AMPs) are attracting more attention as biological compounds and can be a good template to develop therapeutic agents, including antiviral agents against a variety of viruses. Various AMPs have been characterized from the venom of different venomous animals including scorpions. METHODS: The possible antiviral activities of crude venoms obtained from five Egyptian scorpion species (Leiurus quinquestriatus, Androctonus amoreuxi, A. australis, A. bicolor and Scorpio maurus palmatus) were evaluated by a cell culture method using Huh7.5 cells and the J6/JFH1-P47 strain of HCV. Time-of-addition experiments and inactivation of enzymatic activities of the venoms were carried out to determine the characteristics of the anti-HCV activities. RESULTS: S. maurus palmatus and A. australis venoms showed anti-HCV activities, with 50% inhibitory concentrations (IC(50)) being 6.3 ± 1.6 and 88.3 ± 5.8 μg/ml, respectively. S. maurus palmatus venom (30 μg/ml) impaired HCV infectivity in culture medium, but not inside the cells, through virocidal effect. The anti-HCV activity of this venom was not inhibited by a metalloprotease inhibitor or heating at 60°C. The antiviral activity was directed preferentially against HCV. CONCLUSIONS: S. maurus palmatus venom is considered as a good natural source for characterization and development of novel anti-HCV agents targeting the entry step. To our knowledge, this is the first report describing antiviral activities of Egyptian scorpion venoms against HCV, and may open a new approach towards discovering antiviral compounds derived from scorpion venoms.",2015 Mar 24,"['El-Bitar, Alaa MH', 'Sarhan, Moustafa MH', 'Aoki, Chie', 'Takahara, Yusuke', 'Komoto, Mari', 'Deng, Lin', 'Moustafa, Mohsen A', 'Hotta, Hak']",Virol J,,,True
b443b0e9659665ac9bba473fb6ade9d2efdeffe6,PMC,Local cross-border disease surveillance and control: experiences from the Mekong Basin,http://dx.doi.org/10.1186/s13104-015-1047-6,PMC4374506,25889232,CC BY,"BACKGROUND: The Mekong Basin Disease Surveillance cooperation (MBDS) is one of several sub-regional disease surveillance networks that have emerged in recent years as an approach to transnational cooperation for infectious disease prevention and control. Since 2003 MBDS has pioneered a unique model for local cross-border cooperation. This study examines stakeholders’ perspectives of these MBDS experiences, based on a survey of local managers and semi-structured interviews with MBDS leaders and the central coordinator. RESULTS: Fifteen managers from 12 of 20 paired cross-border sites completed a written survey. They all monitor most or all of the 17 diseases agreed upon for MBDS surveillance information sharing. Fourteen agreed or strongly agreed with statements about the core MBDS values of cooperation, mutual trust, and transparency, and their own contributions to national and regional disease control (average score of 4.4 of 5.0). Respondents felt they implemented well to very well activities related to surveillance reporting (average scores 3.4 to 3.9 of 4.0), using computers for their work (3.9/4.0), and using surveillance data for action (3.8/4.0). Respondents reported that they did worst in implementing research (2.1/4.0) and somewhat poorly for local laboratory testing (2.9/4.0) and local coordination with cross-border counterparts (2.9/4.0), although all 15 maintain a list with contact information for these counterparts and many know their counterparts. Implementation of specified activities within their collective regional action plan was uneven across the cross-border sites. Most respondents reported positive lessons learned about local cooperation, information sharing and joint problem solving, based on trusting relationships with their cross-border counterparts. They recommend expansion of cross-border sites within MBDS and consideration of the cross-border cooperation model by other sub-regional networks. CONCLUSIONS: MBDS has over a decade of experience with its model of local cross-border cooperation in disease surveillance and control. Frontline managers have documented success with this model, strongly support it and recommend its expansion within and beyond the MBDS network. The MBDS cross-border cooperation model is standing the test of time as a solid approach to building and sustaining the public health capabilities needed for disease surveillance and control from the local to national and global levels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13104-015-1047-6) contains supplementary material, which is available to authorized users.",2015 Mar 21,"['Moore, Melinda', 'Dausey, David J']",BMC Res Notes,,,False
24d93589f9edba05a3f0a95b350bc91cb551814a,PMC,Local cross-border disease surveillance and control: experiences from the Mekong Basin,http://dx.doi.org/10.1186/s13104-015-1047-6,PMC4374506,25889232,CC BY,"BACKGROUND: The Mekong Basin Disease Surveillance cooperation (MBDS) is one of several sub-regional disease surveillance networks that have emerged in recent years as an approach to transnational cooperation for infectious disease prevention and control. Since 2003 MBDS has pioneered a unique model for local cross-border cooperation. This study examines stakeholders’ perspectives of these MBDS experiences, based on a survey of local managers and semi-structured interviews with MBDS leaders and the central coordinator. RESULTS: Fifteen managers from 12 of 20 paired cross-border sites completed a written survey. They all monitor most or all of the 17 diseases agreed upon for MBDS surveillance information sharing. Fourteen agreed or strongly agreed with statements about the core MBDS values of cooperation, mutual trust, and transparency, and their own contributions to national and regional disease control (average score of 4.4 of 5.0). Respondents felt they implemented well to very well activities related to surveillance reporting (average scores 3.4 to 3.9 of 4.0), using computers for their work (3.9/4.0), and using surveillance data for action (3.8/4.0). Respondents reported that they did worst in implementing research (2.1/4.0) and somewhat poorly for local laboratory testing (2.9/4.0) and local coordination with cross-border counterparts (2.9/4.0), although all 15 maintain a list with contact information for these counterparts and many know their counterparts. Implementation of specified activities within their collective regional action plan was uneven across the cross-border sites. Most respondents reported positive lessons learned about local cooperation, information sharing and joint problem solving, based on trusting relationships with their cross-border counterparts. They recommend expansion of cross-border sites within MBDS and consideration of the cross-border cooperation model by other sub-regional networks. CONCLUSIONS: MBDS has over a decade of experience with its model of local cross-border cooperation in disease surveillance and control. Frontline managers have documented success with this model, strongly support it and recommend its expansion within and beyond the MBDS network. The MBDS cross-border cooperation model is standing the test of time as a solid approach to building and sustaining the public health capabilities needed for disease surveillance and control from the local to national and global levels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13104-015-1047-6) contains supplementary material, which is available to authorized users.",2015 Mar 21,"['Moore, Melinda', 'Dausey, David J']",BMC Res Notes,,,True
e39549d1d4e49cf191e2c743e6b82b738e3b21f2,PMC,Complex Epidemiology of a Zoonotic Disease in a Culturally Diverse Region: Phylogeography of Rabies Virus in the Middle East,http://dx.doi.org/10.1371/journal.pntd.0003569,PMC4374968,25811659,CC BY,"The Middle East is a culturally and politically diverse region at the gateway between Europe, Africa and Asia. Spatial dynamics of the fatal zoonotic disease rabies among countries of the Middle East and surrounding regions is poorly understood. An improved understanding of virus distribution is necessary to direct control methods. Previous studies have suggested regular trans-boundary movement, but have been unable to infer direction. Here we address these issues, by investigating the evolution of 183 rabies virus isolates collected from over 20 countries between 1972 and 2014. We have undertaken a discrete phylogeographic analysis on a subset of 139 samples to infer where and when movements of rabies have occurred. We provide evidence for four genetically distinct clades with separate origins currently circulating in the Middle East and surrounding countries. Introductions of these viruses have been followed by regular and multidirectional trans-boundary movements in some parts of the region, but relative isolation in others. There is evidence for minimal regular incursion of rabies from Central and Eastern Asia. These data support current initiatives for regional collaboration that are essential for rabies elimination.",2015 Mar 26,"['Horton, Daniel L.', 'McElhinney, Lorraine M.', 'Freuling, Conrad M.', 'Marston, Denise A.', 'Banyard, Ashley C.', 'Goharrriz, Hooman', 'Wise, Emma', 'Breed, Andrew C.', 'Saturday, Greg', 'Kolodziejek, Jolanta', 'Zilahi, Erika', 'Al-Kobaisi, Muhannad F.', 'Nowotny, Norbert', 'Mueller, Thomas', 'Fooks, Anthony R.']",PLoS Negl Trop Dis,,,True
9ea1a900f1243ce3264700e9eec29b402892674c,PMC,Adenoviruses Associated with Acute Respiratory Diseases Reported in Beijing from 2011 to 2013,http://dx.doi.org/10.1371/journal.pone.0121375,PMC4376766,25816320,CC BY,"BACKGROUND: Adenovirus is one of the most common causes of viral acute respiratory infections. To identify the types of human adenoviruses (HAdVs) causing respiratory illness in Beijing, a sentinel surveillance project on the viral aetiology of acute respiratory infection was initiated in 2011. PRINCIPAL FINDINGS: Through the surveillance project, 4617 cases of respiratory infections were identified during 2011-2013. Throat swabs (pharynx and tonsil secretions) were collected from all the patients, and 15 different respiratory viruses were screened by multiplex one-step PCR method. 45 were identified as adenovirus-positive from sporadic and outbreak cases of respiratory infection by a multiplex one-step RT-PCR method, and a total of 21 adenovirus isolates were obtained. Five HAdV types among three species, including HAdV-3 (species HAdV-B), HAdV-4 (species HAdV-E), HAdV-7 (species HAdV-B), HAdV-55 (species HAdV-B), and an undefined HAdV type (species HAdV-C) were identified. The comparison results of the penton base, hexon, and fiber gene sequences of the Beijing HAdV-3, HAdV-4, HAdV-7, and HAdV-55 strains in this study and those from the GenBank database indicated significant spatial and temporal conservation and stability of sequences within the genome; however, the phylogenetic relationship indicated that both strain BJ04 and strain BJ09 isolated in 2012 and 2013, respectively, may have recombined between HAdV-1 genome and HAdV-2 genome within species HAdV-C, indicating intraspecies recombination. CONCLUSIONS: This study confirmed that at least 5 HAdV types including HAdV-3, HAdV-4, HAdV-7, HAdV-55 and an undefined HAdV type were co-circulating and were the causative agents of respiratory tract infections in recent years in Beijing. HAdV-3, HAdV-4, HAdV-7, and HAdV-55 showed the apparent stability of the genomes, while intraspecies recombination was identified in strain BJ04 and BJ09. The recombinants carrying penton base gene of HAdV-1 as well as hexon and fiber genes of HAdV-2 might be a novel type of HAdV worthy of further study.",2015 Mar 27,"['Chen, Meng', 'Zhu, Zhen', 'Huang, Fang', 'Liu, Donglei', 'Zhang, Tiegang', 'Ying, Deng', 'Wu, Jiang', 'Xu, Wenbo']",PLoS One,,,True
3faebf3f78e4b42abd134372119fde0ed298fa4b,PMC,Cleavage of Dicer Protein by I7 Protease during Vaccinia Virus Infection,http://dx.doi.org/10.1371/journal.pone.0120390,PMC4376780,25815818,CC BY,"Dicer is the key component in the miRNA pathway. Degradation of Dicer protein is facilitated during vaccinia virus (VV) infection. A C-terminal cleaved product of Dicer protein was detected in the presence of MG132 during VV infection. Thus, it is possible that Dicer protein is cleaved by a viral protease followed by proteasome degradation of the cleaved product. There is a potential I7 protease cleavage site in the C-terminus of Dicer protein. Indeed, reduction of Dicer protein was detected when Dicer was co-expressed with I7 protease but not with an I7 protease mutant protein lack of the protease activity. Mutation of the potential I7 cleavage site in the C-terminus of Dicer protein resisted its degradation during VV infection. Furthermore, Dicer protein was reduced dramatically by recombinant VV vI7Li after the induction of I7 protease. If VV could facilitate the degradation of Dicer protein, the process of miRNA should be affected by VV infection. Indeed, accumulation of precursor miR122 was detected after VV infection or I7 protease expression. Reduction of miR122 would result in the suppression of HCV sub-genomic RNA replication, and, in turn, the amount of viral proteins. As expected, significant reduction of HCVNS5A protein was detected after VV infection and I7 protease expression. Therefore, our results suggest that VV could cleave Dicer protein through I7 protease to facilitate Dicer degradation, and in turn, suppress the processing of miRNAs. Effect of Dicer protein on VV replication was also studied. Exogenous expression of Dicer protein suppresses VV replication slightly while knockdown of Dicer protein does not affect VV replication significantly.",2015 Mar 27,"['Chen, Jhih-Si', 'Li, Hui-Chun', 'Lin, Shu-I', 'Yang, Chee-Hing', 'Chien, Wan-Yu', 'Syu, Ciao-Ling', 'Lo, Shih-Yen']",PLoS One,,,True
662d865c6858d8e9f3b7f583719579ee0aeabdfb,PMC,Methicillin-Resistant Staphylococcus aureus (MRSA) Contamination in Bedside Surfaces of a Hospital Ward and the Potential Effectiveness of Enhanced Disinfection with an Antimicrobial Polymer Surfactant,http://dx.doi.org/10.3390/ijerph120303026,PMC4377950,25768241,CC BY,"The aim in this study was to assess the effectiveness of a quaternary ammonium chloride (QAC) surfactant in reducing surface staphylococcal contamination in a routinely operating medical ward occupied by patients who had tested positive for methicillin-resistant Staphylococcus aureus (MRSA). The QAC being tested is an antibacterial film that is sprayed onto a surface and can remain active for up to 8 h. A field experimental study was designed with the QAC plus daily hypochlorite cleaning as the experimental group and hypochlorite cleaning alone as the control group. The method of swabbing on moistened surfaces was used for sampling. It was found that 83% and 77% of the bedside surfaces of MRSA-positive and MRSA-negative patients respectively were contaminated with staphylococci at 08:00 hours, and that the staphylococcal concentrations increased by 80% at 1200 h over a 4-hour period with routine ward and clinical activities. Irrespective of the MRSA status of the patients, high-touch surfaces around the bed-units within the studied medical ward were heavily contaminated (ranged 1 to 276 cfu/cm(2) amongst the sites with positive culture) with staphylococcal bacteria including MRSA, despite the implementation of daily hypochlorite wiping. However, the contamination rate dropped significantly from 78% to 11% after the application of the QAC polymer. In the experimental group, the mean staphylococcal concentration of bedside surfaces was significantly (p < 0.0001) reduced from 4.4 ± 8.7 cfu/cm(2) at 08:00 hours to 0.07 ± 0.26 cfu/cm(2) at 12:00 hours by the QAC polymer. The results of this study support the view that, in addition to hypochlorite wiping, the tested QAC surfactant is a potential environmental decontamination strategy for preventing the transmission of clinically important pathogens in medical wards.",2015 Mar 11,"['Yuen, John W. M.', 'Chung, Terence W. K.', 'Loke, Alice Y.']",Int J Environ Res Public Health,,,True
c67580a2c552483f02b5df1f297d110b4263c5c5,PMC,The Burden and Etiology of Community-Onset Pneumonia in the Aging Japanese Population: A Multicenter Prospective Study,http://dx.doi.org/10.1371/journal.pone.0122247,PMC4378946,25822890,CC BY,"BACKGROUND: The increasing burden of pneumonia in adults is an emerging health issue in the era of global population aging. This study was conducted to elucidate the burden of community-onset pneumonia (COP) and its etiologic fractions in Japan, the world’s most aged society. METHODS: A multicenter prospective surveillance for COP was conducted from September 2011 to January 2013 in Japan. All pneumonia patients aged ≥15 years, including those with community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP), were enrolled at four community hospitals on four major islands. The COP burden was estimated based on the surveillance data and national statistics. RESULTS: A total of 1,772 COP episodes out of 932,080 hospital visits were enrolled during the surveillance. The estimated overall incidence rates of adult COP, hospitalization, and in-hospital death were 16.9 (95% confidence interval, 13.6 to 20.9), 5.3 (4.5 to 6.2), and 0.7 (0.6 to 0.8) per 1,000 person-years (PY), respectively. The incidence rates sharply increased with age; the incidence in people aged ≥85 years was 10-fold higher than that in people aged 15-64 years. The estimated annual number of adult COP cases in the entire Japanese population was 1,880,000, and 69.4% were aged ≥65 years. Aspiration-associated pneumonia (630,000) was the leading etiologic category, followed by Streptococcus pneumoniae-associated pneumonia (530,000), Haemophilus influenzae-associated pneumonia (420,000), and respiratory virus-associated pneumonia (420,000), including influenza-associated pneumonia (30,000). CONCLUSIONS: A substantial portion of the COP burden occurs among elderly members of the Japanese adult population. In addition to the introduction of effective vaccines for S. pneumoniae and influenza, multidimensional approaches are needed to reduce the pneumonia burden in an aging society.",2015 Mar 30,"['Morimoto, Konosuke', 'Suzuki, Motoi', 'Ishifuji, Tomoko', 'Yaegashi, Makito', 'Asoh, Norichika', 'Hamashige, Naohisa', 'Abe, Masahiko', 'Aoshima, Masahiro', 'Ariyoshi, Koya', None]",PLoS One,,,True
dc55e7876326722cc7c5ad2a88a8d2217c296596,PMC,"The Clinical and Etiological Characteristics of Influenza-Like Illness (ILI) in Outpatients in Shanghai, China, 2011 to 2013",http://dx.doi.org/10.1371/journal.pone.0119513,PMC4379014,25822885,CC BY,"INTRODUCTION: Clinical and etiological characteristics of influenza-like illness (ILI) in outpatients is poorly understood in the southern temperate region of China. We conducted laboratory-based surveillance of viral etiology for ILI outpatients in Shanghai from January 2011 to December 2013. MATERIALS AND METHODS: Clinical and epidemiological data from ILI outpatients, both children and adults, were collected. A total of 1970 nasopharyngeal swabs were collected and tested for 12 respiratory viruses using multiplex RT-PCR, and the data were analyzed anonymously. RESULTS: All 12 respiratory viruses were detected in the specimens. At least one virus was detected in 32.4% of 1970 specimens analyzed, with 1.1% showing co-infections. The most frequently detected agents were influenza A (11.7%), influenza B (9.6%), and rhinoviruses (3.1%).Other viruses were present at a frequency less than 3.0%. We observed a winter peak in the detection rate in ILI patients during 3 years of surveillance and a summer peak in 2012. HCoV, HADV, and HMPV were detected more frequently in children than in adults. Patients infected with influenza virus experienced higher temperatures, more coughs, running noses, headaches and fatigue than patients infected with other viruses and virus-free patients (p<0.001). CONCLUSIONS: The spectrum, seasonality, age distribution and clinical associations of respiratory virus infections in children and adults with influenza-like illness were analyzed in this study for the first time. To a certain extent, the findings can provide baseline data for evaluating the burden of respiratory virus infection in children and adults in Shanghai. It will also provide clinicians with helpful information about the etiological patterns of outpatients presenting with complaints of acute respiratory syndrome, but further studies should be conducted, and longer-term laboratory-based surveillance would give a better picture of the etiology of ILI.",2015 Mar 30,"['Fu, Yifei', 'Pan, Lifeng', 'Sun, Qiao', 'Zhu, Weiping', 'Zhu, Linying', 'Ye, Chuchu', 'Xue, Caoyi', 'Wang, Yuanping', 'Liu, Qing', 'Ma, Ping', 'Qiu, Huifang']",PLoS One,,,True
384dd8bbc85ce35f5da2b0962523fd2870f03d95,PMC,"The Clinical and Etiological Characteristics of Influenza-Like Illness (ILI) in Outpatients in Shanghai, China, 2011 to 2013",http://dx.doi.org/10.1371/journal.pone.0119513,PMC4379014,25822885,CC BY,"INTRODUCTION: Clinical and etiological characteristics of influenza-like illness (ILI) in outpatients is poorly understood in the southern temperate region of China. We conducted laboratory-based surveillance of viral etiology for ILI outpatients in Shanghai from January 2011 to December 2013. MATERIALS AND METHODS: Clinical and epidemiological data from ILI outpatients, both children and adults, were collected. A total of 1970 nasopharyngeal swabs were collected and tested for 12 respiratory viruses using multiplex RT-PCR, and the data were analyzed anonymously. RESULTS: All 12 respiratory viruses were detected in the specimens. At least one virus was detected in 32.4% of 1970 specimens analyzed, with 1.1% showing co-infections. The most frequently detected agents were influenza A (11.7%), influenza B (9.6%), and rhinoviruses (3.1%).Other viruses were present at a frequency less than 3.0%. We observed a winter peak in the detection rate in ILI patients during 3 years of surveillance and a summer peak in 2012. HCoV, HADV, and HMPV were detected more frequently in children than in adults. Patients infected with influenza virus experienced higher temperatures, more coughs, running noses, headaches and fatigue than patients infected with other viruses and virus-free patients (p<0.001). CONCLUSIONS: The spectrum, seasonality, age distribution and clinical associations of respiratory virus infections in children and adults with influenza-like illness were analyzed in this study for the first time. To a certain extent, the findings can provide baseline data for evaluating the burden of respiratory virus infection in children and adults in Shanghai. It will also provide clinicians with helpful information about the etiological patterns of outpatients presenting with complaints of acute respiratory syndrome, but further studies should be conducted, and longer-term laboratory-based surveillance would give a better picture of the etiology of ILI.",2015 Mar 30,"['Fu, Yifei', 'Pan, Lifeng', 'Sun, Qiao', 'Zhu, Weiping', 'Zhu, Linying', 'Ye, Chuchu', 'Xue, Caoyi', 'Wang, Yuanping', 'Liu, Qing', 'Ma, Ping', 'Qiu, Huifang']",PLoS One,,,False
c2b8b47dcfe70db8080da73d7a3941c94b31b025,PMC,Evaluation of ViroCyt(®) Virus Counter for Rapid Filovirus Quantitation,http://dx.doi.org/10.3390/v7030857,PMC4379551,25710889,CC BY,"Development and evaluation of medical countermeasures for diagnostics, vaccines, and therapeutics requires production of standardized, reproducible, and well characterized virus preparations. For filoviruses this includes plaque assay for quantitation of infectious virus, transmission electron microscopy (TEM) for morphology and quantitation of virus particles, and real-time reverse transcription PCR for quantitation of viral RNA (qRT-PCR). The ViroCyt(®) Virus Counter (VC) 2100 (ViroCyt, Boulder, CO, USA) is a flow-based instrument capable of quantifying virus particles in solution. Using a proprietary combination of fluorescent dyes that stain both nucleic acid and protein in a single 30 min step, rapid, reproducible, and cost-effective quantification of filovirus particles was demonstrated. Using a seed stock of Ebola virus variant Kikwit, the linear range of the instrument was determined to be 2.8E+06 to 1.0E+09 virus particles per mL with coefficient of variation ranging from 9.4% to 31.5% for samples tested in triplicate. VC particle counts for various filovirus stocks were within one log of TEM particle counts. A linear relationship was established between the plaque assay, qRT-PCR, and the VC. VC results significantly correlated with both plaque assay and qRT-PCR. These results demonstrated that the VC is an easy, fast, and consistent method to quantify filoviruses in stock preparations.",2015 Feb 20,"['Rossi, Cynthia A.', 'Kearney, Brian J.', 'Olschner, Scott P.', 'Williams, Priscilla L.', 'Robinson, Camenzind G.', 'Heinrich, Megan L.', 'Zovanyi, Ashley M.', 'Ingram, Michael F.', 'Norwood, David A.', 'Schoepp, Randal J.']",Viruses,,,True
b86c0b353d21e4ada6c8cd36da8c433123b23f8e,PMC,Identification of New Respiratory Viruses in the New Millennium,http://dx.doi.org/10.3390/v7030996,PMC4379558,25757061,CC BY,"The rapid advancement of molecular tools in the past 15 years has allowed for the retrospective discovery of several new respiratory viruses as well as the characterization of novel emergent strains. The inability to characterize the etiological origins of respiratory conditions, particularly in children, led several researchers to pursue the discovery of the underlying etiology of disease. In 2001, this led to the discovery of human metapneumovirus (hMPV) and soon following that the outbreak of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) promoted an increased interest in coronavirology and the latter discovery of human coronavirus (HCoV) NL63 and HCoV-HKU1. Human bocavirus, with its four separate lineages, discovered in 2005, has been linked to acute respiratory tract infections and gastrointestinal complications. Middle East Respiratory Syndrome coronavirus (MERS-CoV) represents the most recent outbreak of a completely novel respiratory virus, which occurred in Saudi Arabia in 2012 and presents a significant threat to human health. This review will detail the most current clinical and epidemiological findings to all respiratory viruses discovered since 2001.",2015 Mar 6,"['Berry, Michael', 'Gamieldien, Junaid', 'Fielding, Burtram C.']",Viruses,,,True
a007977dad90a07b3beb9f689e3be8b3f7d2a7f6,PMC,Advanced Molecular Surveillance of Hepatitis C Virus,http://dx.doi.org/10.3390/v7031153,PMC4379565,25781918,CC BY,"Hepatitis C virus (HCV) infection is an important public health problem worldwide. HCV exploits complex molecular mechanisms, which result in a high degree of intrahost genetic heterogeneity. This high degree of variability represents a challenge for the accurate establishment of genetic relatedness between cases and complicates the identification of sources of infection. Tracking HCV infections is crucial for the elucidation of routes of transmission in a variety of settings. Therefore, implementation of HCV advanced molecular surveillance (AMS) is essential for disease control. Accounting for virulence is also important for HCV AMS and both viral and host factors contribute to the disease outcome. Therefore, HCV AMS requires the incorporation of host factors as an integral component of the algorithms used to monitor disease occurrence. Importantly, implementation of comprehensive global databases and data mining are also needed for the proper study of the mechanisms responsible for HCV transmission. Here, we review molecular aspects associated with HCV transmission, as well as the most recent technological advances used for virus and host characterization. Additionally, the cornerstone discoveries that have defined the pathway for viral characterization are presented and the importance of implementing advanced HCV molecular surveillance is highlighted.",2015 Mar 13,"['Gonçalves Rossi, Livia Maria', 'Escobar-Gutierrez, Alejandro', 'Rahal, Paula']",Viruses,,,True
75ad8fc2d398fb3440035eb1a565b060c7ce3a04,PMC,Both ERK1 and ERK2 Are Required for Enterovirus 71 (EV71) Efficient Replication,http://dx.doi.org/10.3390/v7031344,PMC4379574,25803100,CC BY,"It has been demonstrated that MEK1, one of the two MEK isoforms in Raf-MEK-ERK1/2 pathway, is essential for successful EV71 propagation. However, the distinct function of ERK1 and ERK2 isoforms, the downstream kinases of MEKs, remains unclear in EV71 replication. In this study, specific ERK siRNAs and selective inhibitor U0126 were applied. Silencing specific ERK did not significantly impact on the EV71-caused biphasic activation of the other ERK isoform, suggesting the EV71-induced activations of ERK1 and ERK2 were non-discriminative and independent to one another. Knockdown of either ERK1 or ERK2 markedly impaired progeny EV71 propagation (both by more than 90%), progeny viral RNA amplification (either by about 30% to 40%) and protein synthesis (both by around 70%), indicating both ERK1 and ERK2 were critical and not interchangeable to EV71 propagation. Moreover, suppression of EV71 replication by inhibiting both early and late phases of ERK1/2 activation showed no significant difference from that of only blocking the late phase, supporting the late phase activation was more importantly responsible for EV71 life cycle. Taken together, this study for the first time identified both ERK1 and ERK2 were required for EV71 efficient replication and further verified the important role of MEK1-ERK1/2 in EV71 replication.",2015 Mar 20,"['Zhu, Meng', 'Duan, Hao', 'Gao, Meng', 'Zhang, Hao', 'Peng, Yihong']",Viruses,,,True
5931dc46426dbfe8457df3f7c0d8ff406810bd23,PMC,Both ERK1 and ERK2 Are Required for Enterovirus 71 (EV71) Efficient Replication,http://dx.doi.org/10.3390/v7031344,PMC4379574,25803100,CC BY,"It has been demonstrated that MEK1, one of the two MEK isoforms in Raf-MEK-ERK1/2 pathway, is essential for successful EV71 propagation. However, the distinct function of ERK1 and ERK2 isoforms, the downstream kinases of MEKs, remains unclear in EV71 replication. In this study, specific ERK siRNAs and selective inhibitor U0126 were applied. Silencing specific ERK did not significantly impact on the EV71-caused biphasic activation of the other ERK isoform, suggesting the EV71-induced activations of ERK1 and ERK2 were non-discriminative and independent to one another. Knockdown of either ERK1 or ERK2 markedly impaired progeny EV71 propagation (both by more than 90%), progeny viral RNA amplification (either by about 30% to 40%) and protein synthesis (both by around 70%), indicating both ERK1 and ERK2 were critical and not interchangeable to EV71 propagation. Moreover, suppression of EV71 replication by inhibiting both early and late phases of ERK1/2 activation showed no significant difference from that of only blocking the late phase, supporting the late phase activation was more importantly responsible for EV71 life cycle. Taken together, this study for the first time identified both ERK1 and ERK2 were required for EV71 efficient replication and further verified the important role of MEK1-ERK1/2 in EV71 replication.",2015 Mar 20,"['Zhu, Meng', 'Duan, Hao', 'Gao, Meng', 'Zhang, Hao', 'Peng, Yihong']",Viruses,,,False
f1a107788ce585f3f5a7daa6b2eaf55997935192,PMC,Fatal disease associated with Swine Hepatitis E virus and Porcine circovirus 2 co-infection in four weaned pigs in China,http://dx.doi.org/10.1186/s12917-015-0375-z,PMC4379595,25889526,CC BY,"BACKGROUND: In recent decades, Porcine circovirus 2 (PCV2) infection has been recognized as the causative agent of postweaning multisystemic wasting syndrome, and has become a threat to the swine industry. Hepatitis E virus (HEV) is another high prevalent pathogen in swine in many regions of the world. PCV2 and HEV are both highly prevalent in pig farms in China. CASE PRESENTATION: In this study, we characterized the HEV and PCV2 co-infection in 2–3 month-old piglets, based on pathogen identification and the pathological changes observed, in Hebei Province, China. The pathological changes were severe, and general hyperemia, hemorrhage, inflammatory cell infiltration, and necrosis were evident in the tissues of dead swine. PCR was used to identify the pathogen and we tested for eight viruses (HEV, Porcine reproductive and respiratory syndrome virus, PCV2, Classical swine fever virus, Porcine epidemic diarrhea virus, Transmissible gastroenteritis coronavirus, Porcine parvovirus and Pseudorabies virus) that are prevalent in Chinese pig farms. The livers, kidneys, spleens, and other organs of the necropsied swine were positive for HEV and/or PCV2. Immunohistochemical staining showed HEV- and PCV2-antigen-positive signals in the livers, kidneys, lungs, lymph nodes, and intestine. CONCLUSION: HEV and PCV2 co-infection in piglets was detected in four out of seven dead pigs from two pig farms in Hebei, China, producing severe pathological changes. The natural co-infection of HEV and PCV2 in pigs in China has rarely been reported. We speculate that co-infection with PCV2 and HEV may bring some negative effect on pig production and recommend that more attention should be paid to this phenomenon.",2015 Mar 26,"['Yang, Yifei', 'Shi, Ruihan', 'She, Ruiping', 'Mao, Jingjing', 'Zhao, Yue', 'Du, Fang', 'Liu, Can', 'Liu, Jianchai', 'Cheng, Minheng', 'Zhu, Rining', 'Li, Wei', 'Wang, Xiaoyang', 'Soomro, Majid Hussain']",BMC Vet Res,,,True
b5ac1d6f75cea098965bf8e6cfe492b1fab346c6,PMC,Molecular characterization and phylogenetic analysis of transmissible gastroenteritis virus HX strain isolated from China,http://dx.doi.org/10.1186/s12917-015-0387-8,PMC4379598,25890036,CC BY,"BACKGROUND: Porcine transmissible gastroenteritis virus (TGEV) is the major etiological agent of viral enteritis and severe diarrhea in suckling piglets. In China, TGEV has caused great economic losses, but its role in epidemic diarrhea is unclear. This study aims to reveal the etiological role of TGEV in piglet diarrhea via molecular characterization and phylogenetic analysis. RESULTS: A TGEV-HX strain was isolated from China, and its complete genome was amplified, cloned, and sequenced. Sequence analysis indicated that it was conserved in the 5′ and 3′-non-translated regions, and there were no insertions or deletions in nonstructural genes, such as ORF1a, ORF1b, ORF3a, ORF3b, and ORF7, as well as in genes encoding structural proteins, such as the envelope (E), membrane (M), and nucleoprotein (N) proteins. Furthermore, the phylogenetic analysis indicated that the TGEV-HX strain was more similar to the TGEV Purdue cluster than to the Miller cluster. CONCLUSIONS: The present study described the isolation and genetic characterization of a TGEV-HX strain. The detailed analysis of the genetic variation of TGEVs in China provides essential information for further understanding the evolution of TGEVs.",2015 Mar 21,"['Hu, Xiaoliang', 'Li, Nannan', 'Tian, Zhige', 'Yin, Xin', 'Qu, Liandong', 'Qu, Juanjuan']",BMC Vet Res,,,True
da26991502da97b746b148ad17cb2b435ef8e0cb,PMC,Genome and Infection Characteristics of Human Parechovirus Type 1: The Interplay between Viral Infection and Type I Interferon Antiviral System,http://dx.doi.org/10.1371/journal.pone.0116158,PMC4380134,25646764,CC BY,"Human parechoviruses (HPeVs), members of the family Picornaviridae, are associated with severe human clinical conditions such as gastrointestinal disease, encephalitis, meningitis, respiratory disease and neonatal sepsis. A new contemporary strain of HPeV1, KVP6 (accession no. KC769584), was isolated from a clinical specimen. Full-genome alignment revealed that HPeV1 KVP6 shares high genome homology with the German strain of HPeV1, 7555312 (accession no. FM178558) and could be classified in the clade 1B group. An intertypic recombination was shown within the P2-P3 genome regions of HPeV1. Cell-type tropism test showed that T84 cells (colon carcinoma cells), A549 cells (lung carcinoma cells) and DBTRG-5MG cells (glioblastoma cells) were susceptible to HPeV1 infection, which might be relevant clinically. A facilitated cytopathic effect and increased viral titers were reached after serial viral passages in Vero cells, with viral genome mutation found in later passages. HPeV1 is sensitive to elevated temperature because 39°C incubation impaired virion production. HPeV1 induced innate immunity with phosphorylation of interferon (IFN) regulatory transcription factor 3 and production of type I IFN in A549 but not T84 cells. Furthermore, type I IFN inhibited HPeV1 production in A549 cells but not T84 cells; T84 cells may be less responsive to type I IFN stimulation. Moreover, HPeV1-infected cells showed downregulated type I IFN activation, which indicated a type I IFN evasion mechanism. The characterization of the complete genome and infection features of HPeV1 provide comprehensive information about this newly isolated HPeV1 for further diagnosis, prevention or treatment strategies.",2015 Feb 3,"['Chang, Jenn-Tzong', 'Yang, Chih-Shiang', 'Chen, Yao-Shen', 'Chen, Bao-Chen', 'Chiang, An-Jen', 'Chang, Yu-Hsiang', 'Tsai, Wei-Lun', 'Lin, You-Sheng', 'Chao, David', 'Chang, Tsung-Hsien']",PLoS One,,,True
8d81ebbd42382fd503dc2aaf88eb5f790ddebe64,PMC,Identify-Isolate-Inform: A Tool for Initial Detection and Management of Measles Patients in the Emergency Department,http://dx.doi.org/10.5811/westjem.2015.3.25678,PMC4380368,25834659,CC BY,"Measles (rubeola) is a highly contagious airborne disease that was declared eliminated in the U.S. in the year 2000. Only sporadic U.S. cases and minor outbreaks occurred until the larger outbreak beginning in 2014 that has become a public health emergency. The “Identify-Isolate-Inform” tool will assist emergency physicians to be better prepared to detect and manage measles patients presenting to the emergency department. Measles typically presents with a prodrome of high fever, and cough/coryza/conjunctivitis, sometimes accompanied by the pathognomonic Koplik spots. Two to four days later, an erythematous maculopapular rash begins on the face and spreads down the body. Suspect patients must be immediately isolated with airborne precautions while awaiting laboratory confirmation of disease. Emergency physicians must rapidly inform the local public health department and hospital infection control personnel of suspected measles cases.",2015 Mar 18,"['Koenig, Kristi L.', 'Alassaf, Wajdan', 'Burns, Michael J.']",West J Emerg Med,,,True
466c7e2cf0d7aae1c4595ce0bb752df2bbaeb033,PMC,Comparison of Schmallenberg virus antibody levels detected in milk and serum from individual cows,http://dx.doi.org/10.1186/s12917-015-0365-1,PMC4381408,25890260,CC BY,"BACKGROUND: Schmallenberg virus (SBV) is a recently emerged virus of ruminants in Europe. Enzyme-linked immunosorbent assays (ELISA) are commonly used to detect SBV-specific antibodies in bulk tank milk samples to monitor herd exposure to infection. However, it has previously been shown that a bulk tank milk sample can test positive even though the majority of cows within the herd are seronegative for SBV antibodies. Development of a pen-side test to detect antibodies in individual milk samples would potentially provide a cheaper test (for which samples are obtained non-invasively) than testing individual serum samples by ELISA. Therefore, the aim of this study was to investigate the agreement between antibody levels measured in milk and serum. RESULTS: Corresponding milk and serum samples from 88 cows in two dairy herds in the UK were tested for presence of immunoglobulin G antibodies to SBV using a commercially-available indirect ELISA. A serum neutralisation test (NT) was also performed as a gold standard assay. The ELISA values obtained for the bulk tank milk samples corresponded with the mean values for individual milk samples from each herd (bulk tank milk values were 58% and 73% and mean individual milk values 50% and 63% for herds A and B, respectively). Of the 88 serum samples tested in the NT, 82 (93%) were positive. Although at higher antibody levels, the ELISA values tended to be higher for the individual milk samples than for the corresponding serum samples, the positive predictive value for milk samples was 98% and for serum samples 94%. The serum ELISA was more likely to give false positive results around the lower cut-off value of the assay. CONCLUSIONS: The results indicate that testing of individual milk samples for antibodies against SBV by ELISA could be used to inform decisions in the management of dairy herds such as which, if any, animals to vaccinate.",2015 Mar 11,"['Daly, Janet M', 'King, Barnabas', 'Tarlinton, Rachael A', 'Gough, Kevin C', 'Maddison, Ben C', 'Blowey, Roger']",BMC Vet Res,,,True
c9708301ac6326b1214f31ab93fcd4b72485cf4b,PMC,GCN5 inhibits XBP-1S-mediated transcription by antagonizing PCAF action,,PMC4381594,25426559,CC BY,"Cellular unfolded protein response (UPR) is induced when endoplasmic reticulum (ER) is under stress. XBP-1S, the active isoform of X-box binding protein 1 (XBP-1), is a key regulator of UPR. Previously, we showed that a histone acetyltransferase (HAT), p300/CBP-associated factor (PCAF), binds to XBP-1S and functions as an activator of XBP-1S. Here, we identify general control nonderepressible 5 (GCN5), a HAT with 73% identity to PCAF, as a novel XBP-1S regulator. Both PCAF and GCN5 bind to the same domain of XBP-1S. Surprisingly, GCN5 potently blocks the XBP-1S-mediated transcription, including cellular UPR genes and latent membrane protein 1 of Epstein-Barr virus. Unlike PCAF, GCN5 acetylates XBP-1S and enhances nuclear retention and protein stability of XBP-1S. However, such GCN5-mediated acetylation of XBP-1S shows no effects on XBP-1S activity. In addition, the HAT activity of GCN5 is not required for repression of XBP-1S target genes. We further demonstrate that GCN5 inhibits XBP-1S-mediated transcription by disrupting the PCAF-XBP-1S interaction and preventing the recruitment of XBP-1S to its target genes. Taken together, our results represent the first work demonstrating that GCN5 and PCAF exhibit different functions and antagonistically regulate the XBP-1S-mediated transcription.",2014 Nov 16,"['Lew, Qiao Jing', 'Chu, Kai Ling', 'Chia, Yi Ling', 'Soo, Benjamin', 'Ho, Jia Pei', 'Ng, Chew Har', 'Kwok, Hui Si', 'Chiang, Cheng-Ming', 'Chang, Yao', 'Chao, Sheng-Hao']",Oncotarget,,,True
7ad58eb8a34fab3f8ca60410bf583454f7c1128a,PMC,GCN5 inhibits XBP-1S-mediated transcription by antagonizing PCAF action,,PMC4381594,25426559,CC BY,"Cellular unfolded protein response (UPR) is induced when endoplasmic reticulum (ER) is under stress. XBP-1S, the active isoform of X-box binding protein 1 (XBP-1), is a key regulator of UPR. Previously, we showed that a histone acetyltransferase (HAT), p300/CBP-associated factor (PCAF), binds to XBP-1S and functions as an activator of XBP-1S. Here, we identify general control nonderepressible 5 (GCN5), a HAT with 73% identity to PCAF, as a novel XBP-1S regulator. Both PCAF and GCN5 bind to the same domain of XBP-1S. Surprisingly, GCN5 potently blocks the XBP-1S-mediated transcription, including cellular UPR genes and latent membrane protein 1 of Epstein-Barr virus. Unlike PCAF, GCN5 acetylates XBP-1S and enhances nuclear retention and protein stability of XBP-1S. However, such GCN5-mediated acetylation of XBP-1S shows no effects on XBP-1S activity. In addition, the HAT activity of GCN5 is not required for repression of XBP-1S target genes. We further demonstrate that GCN5 inhibits XBP-1S-mediated transcription by disrupting the PCAF-XBP-1S interaction and preventing the recruitment of XBP-1S to its target genes. Taken together, our results represent the first work demonstrating that GCN5 and PCAF exhibit different functions and antagonistically regulate the XBP-1S-mediated transcription.",2014 Nov 16,"['Lew, Qiao Jing', 'Chu, Kai Ling', 'Chia, Yi Ling', 'Soo, Benjamin', 'Ho, Jia Pei', 'Ng, Chew Har', 'Kwok, Hui Si', 'Chiang, Cheng-Ming', 'Chang, Yao', 'Chao, Sheng-Hao']",Oncotarget,,,False
4d4b94ef0c1fb8139c207f5cd7fe3037747fd551,PMC,The Placental Protein Syncytin-1 Impairs Antiviral Responses and Exaggerates Inflammatory Responses to Influenza,http://dx.doi.org/10.1371/journal.pone.0118629,PMC4382184,25831059,CC BY,"BACKGROUND: Pregnancy increases susceptibility to influenza. The placenta releases an immunosuppressive endogenous retroviral protein syncytin-1. We hypothesised that exposure of peripheral monocytes (PBMCs) to syncytin-1 would impair responses to H1N1pdm09 influenza. METHODS AND FINDINGS: Recombinant syncytin-1 was produced. PBMCs from non-pregnant women (n=10) were exposed to H1N1pdm09 in the presence and absence of syncytin-1 and compared to responses of PBMCs from pregnant women (n=12). PBMCs were characterised using flow cytometry, release of interferon (IFN)-α, IFN-λ, IFN-γ, IL-10, IL-2, IL-6 and IL-1β were measured by cytometric bead array or ELISA. Exposure of PBMCs to H1N1pdm09 resulted in the release of IFN-α, (14,787 pg/mL, 95% CI 7311-22,264 pg/mL) IFN-λ (1486 pg/mL, 95% CI 756-2216 pg/mL) and IFN-γ (852 pg/mL, 95% CI 193-1511 pg/mL) after 48 hours. This was significantly impaired in pregnant women (IFN-α; p<0.0001 and IFN-λ; p<0.001). Furthermore, in the presence of syncytin-1, PBMCs demonstrated marked reductions in IFN-α and IFN-λ, while enhanced release of IL-10 as well as IL-6 and IL-1β. CONCLUSIONS: Our data indicates that a placental derived protein, syncytin-1 may be responsible for the heightened vulnerability of pregnant women to influenza.",2015 Apr 1,"['Tolosa, Jorge M.', 'Parsons, Kristy S.', 'Hansbro, Philip M.', 'Smith, Roger', 'Wark, Peter A. B.']",PLoS One,,,True
ffa5a409662570035722ecdd262f2b100601da74,PMC,Efficacy and safety of Ban-Lan-Gen granules in the treatment of seasonal influenza: study protocol for a randomized controlled trial,http://dx.doi.org/10.1186/s13063-015-0645-x,PMC4383212,25873046,CC BY,"BACKGROUND: Ban-Lan-Gen (BLG) is a traditional Chinese herbal medicine. It has been used for the prevention and treatment of virus-related respiratory diseases such as influenza virus infection. BLG contains some antiviral compounds, but few evidence-based clinical studies have been conducted to assess its efficacy against influenza. We assessed the effects of BLG (including efficacy and safety) on the treatment of seasonal influenza in an evidence-based clinical trial. METHODS/DESIGN: We conducted a randomized, double-blinded, oseltamivir- and placebo-controlled, parallel-design clinical trial. A total of 177 subjects are going to be recruited after satisfying the criteria: (i) 18 to 65 years of age; (ii) illness onset within 36 h; (3) axillary temperature ≥38.0°C; and (iv) positive influenza (type A/B) virus test. Subjects will be assigned randomly into three groups in equal proportions: oseltamivir treatment, BLG granule treatment, and placebo treatment. Each group receives 5-day treatment and is followed up 1, 3, 5, 7 and 21 days later. Symptoms and patient compliance are recorded, and virus/serum viral antibodies tested. We will use the primary outcome, secondary outcome, and safety indicators to evaluate the efficacy and safety of BLG granules in the treatment of seasonal influenza. DISCUSSION: We have described the first clinical trial for treatment using a single herb against influenza A and B viruses in China. We will hold a large-scale clinical trial to comprehensively evaluate the effectiveness and safety of BLG against influenza infection based on the results of this pilot study. And this clinical trial will serve as an example for the study of other traditional herbal medicines in evidence-based clinical trials. TRIAL REGISTRATION: This study has been registered at ClinicalTrials.gov: NCT02232945 (3 September 2014). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-015-0645-x) contains supplementary material, which is available to authorized users.",2015 Mar 28,"['Li, Zheng-tu', 'Li, Li', 'Chen, Ting-ting', 'Li, Chu-yuan', 'Wang, De-qin', 'Yang, Zi-feng', 'Zhong, Nan-shan']",Trials,,,False
820910bafe8f9bea166fa699f09f71a2c8f28c76,PMC,Efficacy and safety of Ban-Lan-Gen granules in the treatment of seasonal influenza: study protocol for a randomized controlled trial,http://dx.doi.org/10.1186/s13063-015-0645-x,PMC4383212,25873046,CC BY,"BACKGROUND: Ban-Lan-Gen (BLG) is a traditional Chinese herbal medicine. It has been used for the prevention and treatment of virus-related respiratory diseases such as influenza virus infection. BLG contains some antiviral compounds, but few evidence-based clinical studies have been conducted to assess its efficacy against influenza. We assessed the effects of BLG (including efficacy and safety) on the treatment of seasonal influenza in an evidence-based clinical trial. METHODS/DESIGN: We conducted a randomized, double-blinded, oseltamivir- and placebo-controlled, parallel-design clinical trial. A total of 177 subjects are going to be recruited after satisfying the criteria: (i) 18 to 65 years of age; (ii) illness onset within 36 h; (3) axillary temperature ≥38.0°C; and (iv) positive influenza (type A/B) virus test. Subjects will be assigned randomly into three groups in equal proportions: oseltamivir treatment, BLG granule treatment, and placebo treatment. Each group receives 5-day treatment and is followed up 1, 3, 5, 7 and 21 days later. Symptoms and patient compliance are recorded, and virus/serum viral antibodies tested. We will use the primary outcome, secondary outcome, and safety indicators to evaluate the efficacy and safety of BLG granules in the treatment of seasonal influenza. DISCUSSION: We have described the first clinical trial for treatment using a single herb against influenza A and B viruses in China. We will hold a large-scale clinical trial to comprehensively evaluate the effectiveness and safety of BLG against influenza infection based on the results of this pilot study. And this clinical trial will serve as an example for the study of other traditional herbal medicines in evidence-based clinical trials. TRIAL REGISTRATION: This study has been registered at ClinicalTrials.gov: NCT02232945 (3 September 2014). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-015-0645-x) contains supplementary material, which is available to authorized users.",2015 Mar 28,"['Li, Zheng-tu', 'Li, Li', 'Chen, Ting-ting', 'Li, Chu-yuan', 'Wang, De-qin', 'Yang, Zi-feng', 'Zhong, Nan-shan']",Trials,,,False
310122c497498a3be55d1984730142fcf414a4c3,PMC,Efficacy and safety of Ban-Lan-Gen granules in the treatment of seasonal influenza: study protocol for a randomized controlled trial,http://dx.doi.org/10.1186/s13063-015-0645-x,PMC4383212,25873046,CC BY,"BACKGROUND: Ban-Lan-Gen (BLG) is a traditional Chinese herbal medicine. It has been used for the prevention and treatment of virus-related respiratory diseases such as influenza virus infection. BLG contains some antiviral compounds, but few evidence-based clinical studies have been conducted to assess its efficacy against influenza. We assessed the effects of BLG (including efficacy and safety) on the treatment of seasonal influenza in an evidence-based clinical trial. METHODS/DESIGN: We conducted a randomized, double-blinded, oseltamivir- and placebo-controlled, parallel-design clinical trial. A total of 177 subjects are going to be recruited after satisfying the criteria: (i) 18 to 65 years of age; (ii) illness onset within 36 h; (3) axillary temperature ≥38.0°C; and (iv) positive influenza (type A/B) virus test. Subjects will be assigned randomly into three groups in equal proportions: oseltamivir treatment, BLG granule treatment, and placebo treatment. Each group receives 5-day treatment and is followed up 1, 3, 5, 7 and 21 days later. Symptoms and patient compliance are recorded, and virus/serum viral antibodies tested. We will use the primary outcome, secondary outcome, and safety indicators to evaluate the efficacy and safety of BLG granules in the treatment of seasonal influenza. DISCUSSION: We have described the first clinical trial for treatment using a single herb against influenza A and B viruses in China. We will hold a large-scale clinical trial to comprehensively evaluate the effectiveness and safety of BLG against influenza infection based on the results of this pilot study. And this clinical trial will serve as an example for the study of other traditional herbal medicines in evidence-based clinical trials. TRIAL REGISTRATION: This study has been registered at ClinicalTrials.gov: NCT02232945 (3 September 2014). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-015-0645-x) contains supplementary material, which is available to authorized users.",2015 Mar 28,"['Li, Zheng-tu', 'Li, Li', 'Chen, Ting-ting', 'Li, Chu-yuan', 'Wang, De-qin', 'Yang, Zi-feng', 'Zhong, Nan-shan']",Trials,,,True
d8e9ba5b8657f01d92a6da7558aa323fa9ec5539,PMC,Type I Interferon Response Is Delayed in Human Astrovirus Infections,http://dx.doi.org/10.1371/journal.pone.0123087,PMC4383485,25837699,CC BY,"Type I interferon (IFN) activation and its subsequent effects are important in the response to viral infections. Here we show that human astroviruses (HAstVs), which are important agents of acute gastroenteritis in children, induce a mild and delayed IFN response upon infecting CaCo-2 cells. Although IFN-β mRNA is detected within infected cells and supernatant from infected cells show antiviral activity against the replication of other well-known IFN-sensitive viruses, these responses occur at late stages of infection once genome replication has taken place. On the other hand, HAstV replication can be partially reduced by the addition of exogenous IFN, and inhibition of IFN activation by BX795 enhances viral replication, indicating that HAstVs are IFN-sensitive viruses. Finally, different levels of IFN response were observed in cells infected with different HAstV mutants with changes in the hypervariable region of nsP1a/4, suggesting that nsP1a/4 genotype may potentially have clinical implications due to its correlation with the viral replication phenotype and the antiviral responses induced within infected cells.",2015 Apr 2,"['Guix, Susana', 'Pérez-Bosque, Anna', 'Miró, Lluïsa', 'Moretó, Miquel', 'Bosch, Albert', 'Pintó, Rosa M.']",PLoS One,,,True
becb2b5961d536efc8f0a0b535aeaf7e78d3d273,PMC,Sensitivity and Specificity of a Novel Classifier for the Early Diagnosis of Dengue,http://dx.doi.org/10.1371/journal.pntd.0003638,PMC4383489,25836753,CC BY,"BACKGROUND: Dengue is the commonest arboviral disease of humans. An early and accurate diagnosis of dengue can support clinical management, surveillance and disease control and is central to achieving the World Health Organisation target of a 50% reduction in dengue case mortality by 2020. METHODS: 5729 children with fever of <72hrs duration were enrolled into this multicenter prospective study in southern Vietnam between 2010-2012. A composite of gold standard diagnostic tests identified 1692 dengue cases. Using statistical methods, a novel Early Dengue Classifier (EDC) was developed that used patient age, white blood cell count and platelet count to discriminate dengue cases from non-dengue cases. RESULTS: The EDC had a sensitivity of 74.8% (95%CI: 73.0-76.8%) and specificity of 76.3% (95%CI: 75.2-77.6%) for the diagnosis of dengue. As an adjunctive test alongside NS1 rapid testing, sensitivity of the composite test was 91.6% (95%CI: 90.4-92.9%). CONCLUSIONS: We demonstrate that the early diagnosis of dengue can be enhanced beyond the current standard of care using a simple evidence-based algorithm. The results should support patient management and clinical trials of specific therapies.",2015 Apr 2,"['Tuan, Nguyen Minh', 'Nhan, Ho Thi', 'Chau, Nguyen Van Vinh', 'Hung, Nguyen Thanh', 'Tuan, Ha Manh', 'Tram, Ta Van', 'Ha, Nguyen Le Da', 'Loi, Phan', 'Quang, Han Khoi', 'Kien, Duong Thi Hue', 'Hubbard, Sonya', 'Chau, Tran Nguyen Bich', 'Wills, Bridget', 'Wolbers, Marcel', 'Simmons, Cameron P.']",PLoS Negl Trop Dis,,,True
29e893a01ad314a8432d5948be971e13e48b9103,PMC,A Rational Approach to Estimating the Surgical Demand Elasticity Needed to Guide Manpower Reallocation during Contagious Outbreaks,http://dx.doi.org/10.1371/journal.pone.0122625,PMC4383619,25837596,CC BY,"BACKGROUND: Emerging infectious diseases continue to pose serious threats to global public health. So far, however, few published study has addressed the need for manpower reallocation needed in hospitals when such a serious contagious outbreak occurs. AIM: To quantify the demand elasticity of the major surgery types in order to guide future manpower reallocation during contagious outbreaks. MATERIALS AND METHODS: Based on a nationwide research database in Taiwan, we extracted the monthly volumes of major surgery types for the period 1998–2003, which covered the SARS period, in order to carry out a time series analysis. The demand elasticity of each surgery type was then estimated by autoregressive integrated moving average (ARIMA) analysis. RESULTS: During the study period, the surgical volumes of most selected surgery types either increased or remained steady. We categorized these surgery types into low-, moderate- and high-elastic groups according to their demand elasticity. Appendectomy, ‘open reduction of fracture with internal fixation’ and ‘free skin graft’ were in the low demand elasticity group. Transurethral prostatectomy and extracorporeal shockwave lithotripsy (ESWL) were in the high demand elasticity group. The manpower of the departments carrying out the surgeries with low demand elasticity should be maintained during outbreaks. In contrast, departments in charge of surgeries mainly with high demand elasticity, like urology departments, may be in a position to have part of their staff reallocated. CONCLUSIONS: Taking advantage of the demand variation during the SARS period in 2003, we adopted the concept of demand elasticity and used a time series approach to figure out an effective index of demand elasticity for various types of surgery that could be used as a rational reference to carry out manpower reallocation during contagious outbreak situations.",2015 Apr 2,"['Tsao, Hsiao-Mei', 'Sun, Ying-Chou', 'Liou, Der-Ming']",PLoS One,,,True
b81a921bc4d2223e69b7fddf4f1d2a3ba7622f92,PMC,Transcriptional Regulation of Chemokine Expression in Ovarian Cancer,http://dx.doi.org/10.3390/biom5010223,PMC4384120,25790431,CC BY,"The increased expression of pro-inflammatory and pro-angiogenic chemokines contributes to ovarian cancer progression through the induction of tumor cell proliferation, survival, angiogenesis, and metastasis. The substantial potential of these chemokines to facilitate the progression and metastasis of ovarian cancer underscores the need for their stringent transcriptional regulation. In this Review, we highlight the key mechanisms that regulate the transcription of pro-inflammatory chemokines in ovarian cancer cells, and that have important roles in controlling ovarian cancer progression. We further discuss the potential mechanisms underlying the increased chemokine expression in drug resistance, along with our perspective for future studies.",2015 Mar 17,"['Singha, Bipradeb', 'Gatla, Himavanth R.', 'Vancurova, Ivana']",Biomolecules,,,True
ad4f830c6a0985b878a66d4e797232ccba91aedc,PMC,Targeting a ribonucleoprotein complex containing the caprin-1 protein and the c-Myc mRNA suppresses tumor growth in mice: an identification of a novel oncotarget,,PMC4385842,25669982,CC BY,"Tylophorine compounds have been the focus of drug development for decades. Tylophorine derivatives exhibit anti-cancer activities but their cellular targets remain unknown. We used a biotinylated tylophorine derivative to probe for the interacting cellular target(s) of tylophorine. Tylophorine directly binds to caprin-1 and consequently enhances the recruitment of G3BP1, c-Myc mRNA, and cyclin D2 mRNA to form a ribonucleoprotein complex. Subsequently, this tylophorine targeted ribonucleoprotein complex is sequestered to the polysomal fractions and the protein expressions of the associated mRNA-transcripts are repressed. Caprin-1 depleted carcinoma cells become more resistant to tylophorine, associated with decreased formation of the ribonucleoprotein complex targeted by tylophorine. Consequently, tylophorine downregulates c-Myc and cyclins D1/D2, causing hypophosphorylation of Rb and suppression of both processing-body formation and the Warburg effect. Gene expression profiling and gain-of-c-Myc-function experiments also revealed that the downregulated c-Myc contributes to the anti-oncogenic effects of tylophorine compounds. Furthermore, the potent tylophorine derivative dibenzoquinoline-33b elicited a similar effect, as c-Myc protein levels were also decreased in xenograft tumors treated with dibenzoquinoline-33b. Thus, tylophorine compounds exert anti-cancer activity predominantly by targeting and sequestering the caprin-1 protein and c-Myc mRNA associated ribonucleoprotein complex.",2014 Dec 10,"['Qiu, Ya-Qi', 'Yang, Cheng-Wei', 'Lee, Yue-Zhi', 'Yang, Ruey-Bing', 'Lee, Chih-Hao', 'Hsu, Hsing-Yu', 'Chang, Chien-Chung', 'Lee, Shiow-Ju']",Oncotarget,,,True
9de48553eac5b5676f0e796f544e04634d39aaa4,PMC,Targeting a ribonucleoprotein complex containing the caprin-1 protein and the c-Myc mRNA suppresses tumor growth in mice: an identification of a novel oncotarget,,PMC4385842,25669982,CC BY,"Tylophorine compounds have been the focus of drug development for decades. Tylophorine derivatives exhibit anti-cancer activities but their cellular targets remain unknown. We used a biotinylated tylophorine derivative to probe for the interacting cellular target(s) of tylophorine. Tylophorine directly binds to caprin-1 and consequently enhances the recruitment of G3BP1, c-Myc mRNA, and cyclin D2 mRNA to form a ribonucleoprotein complex. Subsequently, this tylophorine targeted ribonucleoprotein complex is sequestered to the polysomal fractions and the protein expressions of the associated mRNA-transcripts are repressed. Caprin-1 depleted carcinoma cells become more resistant to tylophorine, associated with decreased formation of the ribonucleoprotein complex targeted by tylophorine. Consequently, tylophorine downregulates c-Myc and cyclins D1/D2, causing hypophosphorylation of Rb and suppression of both processing-body formation and the Warburg effect. Gene expression profiling and gain-of-c-Myc-function experiments also revealed that the downregulated c-Myc contributes to the anti-oncogenic effects of tylophorine compounds. Furthermore, the potent tylophorine derivative dibenzoquinoline-33b elicited a similar effect, as c-Myc protein levels were also decreased in xenograft tumors treated with dibenzoquinoline-33b. Thus, tylophorine compounds exert anti-cancer activity predominantly by targeting and sequestering the caprin-1 protein and c-Myc mRNA associated ribonucleoprotein complex.",2014 Dec 10,"['Qiu, Ya-Qi', 'Yang, Cheng-Wei', 'Lee, Yue-Zhi', 'Yang, Ruey-Bing', 'Lee, Chih-Hao', 'Hsu, Hsing-Yu', 'Chang, Chien-Chung', 'Lee, Shiow-Ju']",Oncotarget,,,True
3bc7abde53bcbdc7ca555c835d5ad34a67941a80,PMC,"The eEF1A Proteins: At the Crossroads of Oncogenesis, Apoptosis, and Viral Infections",http://dx.doi.org/10.3389/fonc.2015.00075,PMC4387925,25905039,CC BY,"Eukaryotic translation elongation factors 1 alpha, eEF1A1 and eEF1A2, are not only translation factors but also pleiotropic proteins that are highly expressed in human tumors, including breast cancer, ovarian cancer, and lung cancer. eEF1A1 modulates cytoskeleton, exhibits chaperone-like activity and also controls cell proliferation and cell death. In contrast, eEF1A2 protein favors oncogenesis as shown by the fact that overexpression of eEF1A2 leads to cellular transformation and gives rise to tumors in nude mice. The eEF1A2 protein stimulates the phospholipid signaling and activates the Akt-dependent cell migration and actin remodeling that ultimately favors tumorigenesis. In contrast, inactivation of eEF1A proteins leads to immunodeficiency, neural and muscular defects, and favors apoptosis. Finally, eEF1A proteins interact with several viral proteins resulting in enhanced viral replication, decreased apoptosis, and increased cellular transformation. This review summarizes the recent findings on eEF1A proteins indicating that eEF1A proteins play a critical role in numerous human diseases through enhancement of oncogenesis, blockade of apoptosis, and increased viral pathogenesis.",2015 Apr 7,"['Abbas, Wasim', 'Kumar, Amit', 'Herbein, Georges']",Front Oncol,,,True
c3334a3ad6a9e88664342aff618229775fb3e31a,PMC,Leukocyte-Derived IFN-α/β and Epithelial IFN-λ Constitute a Compartmentalized Mucosal Defense System that Restricts Enteric Virus Infections,http://dx.doi.org/10.1371/journal.ppat.1004782,PMC4388470,25849543,CC BY,"Epithelial cells are a major port of entry for many viruses, but the molecular networks which protect barrier surfaces against viral infections are incompletely understood. Viral infections induce simultaneous production of type I (IFN-α/β) and type III (IFN-λ) interferons. All nucleated cells are believed to respond to IFN-α/β, whereas IFN-λ responses are largely confined to epithelial cells. We observed that intestinal epithelial cells, unlike hematopoietic cells of this organ, express only very low levels of functional IFN-α/β receptors. Accordingly, after oral infection of IFN-α/β receptor-deficient mice, human reovirus type 3 specifically infected cells in the lamina propria but, strikingly, did not productively replicate in gut epithelial cells. By contrast, reovirus replicated almost exclusively in gut epithelial cells of IFN-λ receptor-deficient mice, suggesting that the gut mucosa is equipped with a compartmentalized IFN system in which epithelial cells mainly respond to IFN-λ that they produce after viral infection, whereas other cells of the gut mostly rely on IFN-α/β for antiviral defense. In suckling mice with IFN-λ receptor deficiency, reovirus replicated in the gut epithelium and additionally infected epithelial cells lining the bile ducts, indicating that infants may use IFN-λ for the control of virus infections in various epithelia-rich tissues. Thus, IFN-λ should be regarded as an autonomous virus defense system of the gut mucosa and other epithelial barriers that may have evolved to avoid unnecessarily frequent triggering of the IFN-α/β system which would induce exacerbated inflammation.",2015 Apr 7,"['Mahlakõiv, Tanel', 'Hernandez, Pedro', 'Gronke, Konrad', 'Diefenbach, Andreas', 'Staeheli, Peter']",PLoS Pathog,,,True
c90c4e5ca7134a20586234aae4f4f8b6b42c05fe,PMC,Unlocking Patients with Mental Disorders Who Were in Restraints at Home: A National Follow-Up Study of China’s New Public Mental Health Initiatives,http://dx.doi.org/10.1371/journal.pone.0121425,PMC4388503,25848800,CC BY,"BACKGROUND: In 2005, China implemented a demonstration program known as “686” to scale-up nation-wide basic mental health services designed to improve access to evidence-based care and to promote human rights for people with severe mental disorders. As part of the 686 Program, teams “unlocked” and provided continuous mental health care to people with severe mental disorders who were found in restraints and largely untreated in their family homes. We implemented a nation-wide two-stage follow-up study to measure the effectiveness and sustainability of the “unlocking and treatment” intervention and its impact on the well-being of patients’ families. METHODS: 266 patients unlocked from 2005 in “686” demonstration sites across China were recruited in Stage One of the study in 2009. In 2012, 230 of the 266 cases were re-interviewed (the Stage Two study). Outcome measures included the patient medication adherence and social functioning, family burden ratings, and relocking rate. We utilized pre-post tests to analyze the changes over time following the unlocking efforts. RESULTS: 96% of patients were diagnosed with schizophrenia. Prior to unlocking, their total time locked ranged from two weeks to 28 years, with 32% having been locked multiple times. The number of persons regularly taking medicines increased from one person at the time of unlocking to 74% in 2009 and 76% in 2012. Pre-post tests showed sustained improvement in patient social functioning and significant reductions in family burden. Over 92% of patients remained free of restraints in 2012. CONCLUSION: Practice-based evidence from our study suggests an important model for protecting the human rights of people with mental disorders and keeping them free of restraints can be achieved by providing accessible, community based mental health services with continuity of care. China’s “686” Program can inform similar efforts in low-resource settings where community locking of patients is practiced.",2015 Apr 7,"['Guan, Lili', 'Liu, Jin', 'Wu, Xia Min', 'Chen, Dafang', 'Wang, Xun', 'Ma, Ning', 'Wang, Yan', 'Good, Byron', 'Ma, Hong', 'Yu, Xin', 'Good, Mary-Jo']",PLoS One,,,True
8111c472b27463ca0dfae56c5196eb4c92fdd14f,PMC,Studying the effect of chloroquine on sporozoite-induced protection and immune responses in Plasmodium berghei malaria,http://dx.doi.org/10.1186/s12936-015-0626-2,PMC4389414,25889324,CC BY,"BACKGROUND: Sporozoite immunization of animals and humans under a chemo-prophylactic cover of chloroquine (CPS-CQ) efficiently induces sterile protection against malaria. In humans, CPS-CQ is strikingly more efficient than immunization with radiation attenuated sporozoites (RAS), raising the hypothesis that this might be partially due to CQ. Chloroquine, an established anti-malarial drug, is also well known for its immune modulating properties including improvement of cross-presentation. The aim of this study was to investigate whether co-administration of CQ during sporozoite immunization improves cellular responses and protective efficacy in Plasmodium berghei models. METHODS: A number of experiments in selected complimentary P. berghei murine models in Balb/cByJ and C57BL/6j mice was performed. First, the effect of CQ administration on the induction of protection and immune responses by RAS immunization was studied. Next, the effect of CQ on the induction of circumsporozoite (CS) protein-specific CD8(+) T cells by immunization with P. berghei parasites expressing a mutant CS protein was investigated. Finally, a direct comparison of CPS-CQ to CPS with mefloquine (MQ), an anti-malarial with little known immune modulating effects, was performed. RESULTS: When CQ was co-administered during immunization with graded numbers of RAS, this did not lead to an increase in frequencies of total memory CD8(+) T cells or CS protein-specific CD8(+) T cells. Also parasite-specific cytokine production and protection remained unaltered. Replacement of CQ by MQ for CPS immunization resulted in significantly reduced percentages of IFNγ producing memory T cells in the liver (p = 0.01), but similar protection. CONCLUSIONS: This study does not provide evidence for a direct beneficial effect of CQ on the induction of sporozoite-induced immune responses and protection in P. berghei malaria models. Alternatively, the higher efficiency of CPS compared to RAS might be explained by an indirect effect of CQ through limiting blood-stage exposure after immunization or to increased antigen exposure and, therefore, improved breadth of the immune response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-015-0626-2) contains supplementary material, which is available to authorized users.",2015 Mar 26,"['Bijker, Else M', 'Nganou-Makamdop, Krystelle', 'van Gemert, Geert-Jan', 'Zavala, Fidel', 'Cockburn, Ian', 'Sauerwein, Robert W']",Malar J,,,True
fdd420ba12ea83c4db57fccfe77d5aad622db3c6,PMC,Analysis of Chemokines and Receptors Expression Profile in the Myelin Mutant Taiep Rat,http://dx.doi.org/10.1155/2015/397310,PMC4390177,25883747,CC BY,"Taiep rat has a failure in myelination and remyelination processes leading to a state of hypomyelination throughout its life. Chemokines, which are known to play a role in inflammation, are also involved in the remyelination process. We aimed to demonstrate that remyelination-stimulating factors are altered in the brainstem of 1- and 6-month-old taiep rats. We used a Rat RT(2) Profiler PCR Array to assess mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors. We also evaluated protein levels of CCL2, CCR1, CCR2, CCL5, CCR5, CCR8, CXCL1, CXCR2, CXCR4, FGF2, and VEGFA by ELISA. Sprague-Dawley rats were used as a control. PCR Array procedure showed that proinflammatory cytokines were not upregulated in the taiep rat. In contrast, some mRNA levels of beta and alpha chemokines were upregulated in 1-month-old rats, but CXCR4 was downregulated at their 6 months of age. ELISA results showed that CXCL1, CCL2, CCR2, CCR5, CCR8, and CXCR4 protein levels were decreased in brainstem at the age of 6 months. These results suggest the presence of a chronic neuroinflammation process with deficiency of remyelination-stimulating factors (CXCL1, CXCR2, and CXCR4), which might account for the demyelination in the taiep rat.",2015 Mar 25,"['Soto-Rodriguez, Guadalupe', 'Gonzalez-Barrios, Juan-Antonio', 'Martinez-Fong, Daniel', 'Blanco-Alvarez, Victor-Manuel', 'Eguibar, Jose R.', 'Ugarte, Araceli', 'Martinez-Perez, Francisco', 'Brambila, Eduardo', 'Millán-Perez Peña, Lourdes', 'Pazos-Salazar, Nidia-Gary', 'Torres-Soto, Maricela', 'Garcia-Robles, Guadalupe', 'Tomas-Sanchez, Constantino', 'Leon-Chavez, Bertha Alicia']",Oxid Med Cell Longev,,,True
3725a278a669559c9fd096a9a7dd5f35c6928c6c,PMC,Target-Dependent Enrichment of Virions Determines the Reduction of High-Throughput Sequencing in Virus Discovery,http://dx.doi.org/10.1371/journal.pone.0122636,PMC4390369,25853649,CC BY,"Viral infections cause many different diseases stemming both from well-characterized viral pathogens but also from emerging viruses, and the search for novel viruses continues to be of great importance. High-throughput sequencing is an important technology for this purpose. However, viral nucleic acids often constitute a minute proportion of the total genetic material in a sample from infected tissue. Techniques to enrich viral targets in high-throughput sequencing have been reported, but the sensitivity of such methods is not well established. This study compares different library preparation techniques targeting both DNA and RNA with and without virion enrichment. By optimizing the selection of intact virus particles, both by physical and enzymatic approaches, we assessed the effectiveness of the specific enrichment of viral sequences as compared to non-enriched sample preparations by selectively looking for and counting read sequences obtained from shotgun sequencing. Using shotgun sequencing of total DNA or RNA, viral targets were detected at concentrations corresponding to the predicted level, providing a foundation for estimating the effectiveness of virion enrichment. Virion enrichment typically produced a 1000-fold increase in the proportion of DNA virus sequences. For RNA virions the gain was less pronounced with a maximum 13-fold increase. This enrichment varied between the different sample concentrations, with no clear trend. Despite that less sequencing was required to identify target sequences, it was not evident from our data that a lower detection level was achieved by virion enrichment compared to shotgun sequencing.",2015 Apr 8,"['Jensen, Randi Holm', 'Mollerup, Sarah', 'Mourier, Tobias', 'Hansen, Thomas Arn', 'Fridholm, Helena', 'Nielsen, Lars Peter', 'Willerslev, Eske', 'Hansen, Anders Johannes', 'Vinner, Lasse']",PLoS One,,,True
5c8e391286fba644689754596eaf50c7f32b5a99,PMC,Molecular Typing and Epidemiology Profiles of Human Adenovirus Infection among Paediatric Patients with Severe Acute Respiratory Infection in China,http://dx.doi.org/10.1371/journal.pone.0123234,PMC4391708,25856575,CC BY,"BACKGROUND: Human adenoviruses (HAdVs) have been recognised as pathogens that cause a broad spectrum of diseases. The studies on HAdV infection among children with severe acute respiratory infection (SARI) are limited. OBJECTIVE: To investigate the prevalence, epidemiology, and genotype of HAdV among children with SARI in China. STUDY DESIGN: Nasopharyngeal aspirates (NPAs) or induced sputum (IS) was collected from hospitalised children with SARIs in Beijing (representing Northern China; n = 259) and Zhejiang Province (representing Eastern China; n = 293) from 2007 to 2010. The prevalence of HAdV was screened by polymerase chain reaction (PCR), followed by sequence typing of PCR fragments that targeted the second half of the hexon gene. In addition, co-infection with other human respiratory viruses, related epidemiological profiles and clinical presentations were investigated. RESULTS AND CONCLUSIONS: In total, 76 (13.8%) of 552 SARI patients were positive for HAdV, and the infection rates of HAdV in Northern and Eastern China were 20.1% (n = 52) and 8.2% (n = 24), respectively. HAdV co-infection with other respiratory viruses was frequent (infection rates: Northern China, 90.4%; Eastern China, 70.8%). The peak seasons for HAdV-B infection was winter and spring. Additionally, members of multiple species (Human mastadenovirus B, C, D and E) were circulating among paediatric patients with SARI, of which HAdV-B (34/52; 65.4%) and HAdV-C (20/24, 83.3%) were the most predominant in Northern and Eastern China, respectively. These findings provide a benchmark for future epidemiology and prevention strategies for HAdV.",2015 Apr 9,"['Li, Yamin', 'Zhou, Weimin', 'Zhao, Yanjie', 'Wang, Yanqun', 'Xie, Zhengde', 'Lou, Yongliang', 'Tan, Wenjie']",PLoS One,,,True
f0f627b8e856fdf97cf414ac42f3536ff1a33134,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,True
4a23c60bc6b2ad215c359eb1cde0e39a02f1c58b,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,False
35441dbff544552c333248073f7b607d589dcf11,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,False
81218b498d85bed08aed26f5528388196e18347f,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,False
066c2d87d87b962f50259df3f1c7ef90cf71f552,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,False
8738048c7fa1a4002ac20dd884f60549188a7bc5,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,False
4123be6939693b4b61698ad16390726cde1f8e83,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,False
a728bd8a56bd0a774f87937ee40356882fbe363e,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,False
73d99b38d24686662faa3bb28bdcd5596e945b2d,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,False
7ed7b23c66b9c4ad156f37619f8b88bc1c1e996b,PMC,Age-Related Onset of Obesity Corresponds with Metabolic Dysregulation and Altered Microglia Morphology in Mice Deficient for Ifitm Proteins,http://dx.doi.org/10.1371/journal.pone.0123218,PMC4391874,25856311,CC0,"The IfitmDel mouse lacks all five of the Ifitm genes via LoxP deletion. This animal breeds normally with no obvious defect in development. The IfitmDel animals exhibit a steady and significantly enhanced weight gain relative to wild-type controls beginning about three months of age and under normal feeding conditions. The increased weight corresponds with elevated fat mass, and in tolerance tests they are hyporesponsive to insulin but respond normally to glucose. Both young (4 mo) and older (12 mo) IfitmDel mice have enhanced levels of serum leptin suggesting a defect in leptin/leptin receptor signaling. Analysis of the gene expression profiles in the hypothalamus of IfitmDel animals, compared to WT, demonstrated an altered ratio of Pomc and Npy neuropeptide expression, which likely impairs the satiation response of the IfitmDel animal leading to an increased eating behavior. Also elevated in hypothalamus of IfitmDel mice were pro-inflammatory cytokine expression and reduced IL-10. Anatomical analysis of the hypothalamus using immunohistochemistry revealed that microglia exhibit an abnormal morphology in IfitmDel animals and respond abnormally to Poly:IC challenge. These abnormalities extend the phenotype of the IfitmDel mouse beyond abnormal responses to viral challenge to include a metabolic phenotype and weight gain. Further, this novel phenotype for the IfitmDel mouse could be related to abnormal neuropeptide production, inflammatory status and microglia status in the hypothalamus.",2015 Apr 9,"['Wee, Yin Shen', 'Weis, Janis J.', 'Gahring, Lorise C.', 'Rogers, Scott W.', 'Weis, John H.']",PLoS One,,,True
7b22c0d8cb7675bcc5aa283fe3bfef6c72052519,PMC,Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV),http://dx.doi.org/10.1371/journal.pone.0123126,PMC4391951,25856093,CC0,"The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens.",2015 Apr 9,"['Bhadra, Sanchita', 'Jiang, Yu Sherry', 'Kumar, Mia R.', 'Johnson, Reed F.', 'Hensley, Lisa E.', 'Ellington, Andrew D.']",PLoS One,,,True
638b85191a280fd443ab5cae740b18d9c7a33111,PMC,Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV),http://dx.doi.org/10.1371/journal.pone.0123126,PMC4391951,25856093,CC0,"The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens.",2015 Apr 9,"['Bhadra, Sanchita', 'Jiang, Yu Sherry', 'Kumar, Mia R.', 'Johnson, Reed F.', 'Hensley, Lisa E.', 'Ellington, Andrew D.']",PLoS One,,,False
57ba11d45980a89cf1313f3eab68ad0c77d53439,PMC,Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV),http://dx.doi.org/10.1371/journal.pone.0123126,PMC4391951,25856093,CC0,"The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens.",2015 Apr 9,"['Bhadra, Sanchita', 'Jiang, Yu Sherry', 'Kumar, Mia R.', 'Johnson, Reed F.', 'Hensley, Lisa E.', 'Ellington, Andrew D.']",PLoS One,,,False
ad3f041570cc2b3f4ba0b08e97f03ded08785a03,PMC,Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV),http://dx.doi.org/10.1371/journal.pone.0123126,PMC4391951,25856093,CC0,"The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens.",2015 Apr 9,"['Bhadra, Sanchita', 'Jiang, Yu Sherry', 'Kumar, Mia R.', 'Johnson, Reed F.', 'Hensley, Lisa E.', 'Ellington, Andrew D.']",PLoS One,,,False
d45dd40806dfbd1ca6504db7fc56dc775aff31bc,PMC,Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV),http://dx.doi.org/10.1371/journal.pone.0123126,PMC4391951,25856093,CC0,"The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens.",2015 Apr 9,"['Bhadra, Sanchita', 'Jiang, Yu Sherry', 'Kumar, Mia R.', 'Johnson, Reed F.', 'Hensley, Lisa E.', 'Ellington, Andrew D.']",PLoS One,,,False
2fd9cf0a1317d136ce3e0a14b71cffb6d74e257e,PMC,Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV),http://dx.doi.org/10.1371/journal.pone.0123126,PMC4391951,25856093,CC0,"The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens.",2015 Apr 9,"['Bhadra, Sanchita', 'Jiang, Yu Sherry', 'Kumar, Mia R.', 'Johnson, Reed F.', 'Hensley, Lisa E.', 'Ellington, Andrew D.']",PLoS One,,,False
dd40ad3eec9f455f6ab725f007eb32e852b3439c,PMC,Identification of Appropriate Reference Genes for qRT-PCR Analysis of Heat-Stressed Mammary Epithelial Cells in Riverine Buffaloes (Bubalus bubalis),http://dx.doi.org/10.5402/2013/735053,PMC4393032,25937980,CC BY,"Gene expression studies require appropriate normalization methods for proper evaluation of reference genes. To date, not many studies have been reported on the identification of suitable reference genes in buffaloes. The present study was undertaken to determine the panel of suitable reference genes in heat-stressed buffalo mammary epithelial cells (MECs). Briefly, MEC culture from buffalo mammary gland was exposed to 42 °C for one hour and subsequently allowed to recover at 37 °C for different time intervals (from 30 m to 48 h). Three different algorithms, geNorm, NormFinder, and BestKeeper softwares, were used to evaluate the stability of 16 potential reference genes from different functional classes. Our data identified RPL4, EEF1A1, and RPS23 genes to be the most appropriate reference genes that could be utilized for normalization of qPCR data in heat-stressed buffalo MECs.",2013 Jan 28,"['Kapila, Neha', 'Kishore, Amit', 'Sodhi, Monika', 'Sharma, Ankita', 'Kumar, Pawan', 'Mohanty, A. K.', 'Jerath, Tanushri', 'Mukesh, M.']",ISRN Biotechnol,,,True
e2de7af2f055e3cf79556848d5b6aa2d27c4b97d,PMC,Antiviral Activity and Possible Mechanism of Action of Constituents Identified in Paeonia lactiflora Root toward Human Rhinoviruses,http://dx.doi.org/10.1371/journal.pone.0121629,PMC4393083,25860871,CC BY,"Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cost billions of USD annually in medical visits and missed school and work. An assessment was made of the antiviral activities and mechanisms of action of paeonol (PA) and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) from Paeonia lactiflora root toward HRV-2 and HRV-4 in MRC5 cells using a tetrazolium method and real-time quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results were compared with those of a reference control ribavirin. Based on 50% inhibitory concentration values, PGG was 13.4 and 18.0 times more active toward HRV-2 (17.89 μM) and HRV-4 (17.33 μM) in MRC5 cells, respectively, than ribavirin. The constituents had relatively high selective index values (3.3–>8.5). The 100 μg/mL PA and 20 μg/mL PGG did not interact with the HRV-4 particles. These constituents inhibited HRV-4 infection only when they were added during the virus inoculation (0 h), the adsorption period of HRVs, but not after 1 h or later. Moreover, the RNA replication levels of HRVs were remarkably reduced in the MRC5 cultures treated with these constituents. These findings suggest that PGG and PA may block or reduce the entry of the viruses into the cells to protect the cells from the virus destruction and abate virus replication, which may play an important role in interfering with expressions of rhinovirus receptors (intercellular adhesion molecule-1 and low-density lipoprotein receptor), inflammatory cytokines (interleukin (IL)-6, IL-8, tumor necrosis factor, interferon beta, and IL-1β), and Toll-like receptor, which resulted in diminishing symptoms induced by HRV. Global efforts to reduce the level of synthetic drugs justify further studies on P. lactiflora root-derived materials as potential anti-HRV products or lead molecules for the prevention or treatment of HRV.",2015 Apr 10,"['Ngan, Luong Thi My', 'Jang, Myeong Jin', 'Kwon, Min Jung', 'Ahn, Young Joon']",PLoS One,,,True
e854283ba0d428f16fb5eec6a1ba210ff7925125,PMC,Human alveolar epithelial type II cells in primary culture,http://dx.doi.org/10.14814/phy2.12288,PMC4393197,25677546,CC BY,"Alveolar epithelial type II (AEII) cells are a key structure and defender in the lung but also are the targets in many lung diseases, including acute respiratory distress syndrome, ventilator-induced lung injury, and pulmonary fibrosis. We sought to establish an optimized method for high yielding and long maintenance of characteristics of primary human AEII cells to facilitate the investigation of the mechanisms of lung diseases at the cellular and molecular levels. Adult human peripheral normal lung tissues of oncologic patients undergoing lung resection were collected. The AEII cells were isolated and identified by the expression of pro-surfactant protein (SP)C, epithelial sodium channel (αENaC) and cytokeratin (CK)-8, the lamellar bodies specific for AEII cells, and confirmed by the histology using electron microscopy. The phenotype of AEII cells was characterized by the expression of surfactant proteins (SP-A, SP-B, SP-C, SP-D), CK-8, KL-6, αENaC, and aquaporin (AQP)-3, which was maintained over 20 days. The biological activity of the primary human AEII cells producing SP-C, cytokines, and intercellular adhesion molecule-1 was vigorous in response to stimulation with tumor necrosis factor-α. We have modified previous methods and optimized a method for isolation of high purity and long maintenance of the human AEII cell phenotype in primary culture. This method provides an important tool for studies aiming at elucidating the molecular mechanisms of lung diseases exclusively in AEII cells.",2015 Feb 13,"['Mao, Pu', 'Wu, Songling', 'Li, Jianchun', 'Fu, Wei', 'He, Weiqun', 'Liu, Xiaoqing', 'Slutsky, Arthur S', 'Zhang, Haibo', 'Li, Yimin']",Physiol Rep,,,True
8e8e5b1a4c76cea327ba95e100445f08ffebf9be,PMC,Characterizing the Transmission Potential of Zoonotic Infections from Minor Outbreaks,http://dx.doi.org/10.1371/journal.pcbi.1004154,PMC4393285,25860289,CC BY,"The transmission potential of a novel infection depends on both the inherent transmissibility of a pathogen, and the level of susceptibility in the host population. However, distinguishing between these pathogen- and population-specific properties typically requires detailed serological studies, which are rarely available in the early stages of an outbreak. Using a simple transmission model that incorporates age-stratified social mixing patterns, we present a novel method for characterizing the transmission potential of subcritical infections, which have effective reproduction number R<1, from readily available data on the size of outbreaks. We show that the model can identify the extent to which outbreaks are driven by inherent pathogen transmissibility and pre-existing population immunity, and can generate unbiased estimates of the effective reproduction number. Applying the method to real-life infections, we obtained accurate estimates for the degree of age-specific immunity against monkeypox, influenza A(H5N1) and A(H7N9), and refined existing estimates of the reproduction number. Our results also suggest minimal pre-existing immunity to MERS-CoV in humans. The approach we describe can therefore provide crucial information about novel infections before serological surveys and other detailed analyses are available. The methods would also be applicable to data stratified by factors such as profession or location, which would make it possible to measure the transmission potential of emerging infections in a wide range of settings.",2015 Apr 10,"['Kucharski, Adam J.', 'Edmunds, W. John']",PLoS Comput Biol,,,True
eaf8eeee7e38b2ed41a22554d585903f14262030,PMC,Characterizing the Transmission Potential of Zoonotic Infections from Minor Outbreaks,http://dx.doi.org/10.1371/journal.pcbi.1004154,PMC4393285,25860289,CC BY,"The transmission potential of a novel infection depends on both the inherent transmissibility of a pathogen, and the level of susceptibility in the host population. However, distinguishing between these pathogen- and population-specific properties typically requires detailed serological studies, which are rarely available in the early stages of an outbreak. Using a simple transmission model that incorporates age-stratified social mixing patterns, we present a novel method for characterizing the transmission potential of subcritical infections, which have effective reproduction number R<1, from readily available data on the size of outbreaks. We show that the model can identify the extent to which outbreaks are driven by inherent pathogen transmissibility and pre-existing population immunity, and can generate unbiased estimates of the effective reproduction number. Applying the method to real-life infections, we obtained accurate estimates for the degree of age-specific immunity against monkeypox, influenza A(H5N1) and A(H7N9), and refined existing estimates of the reproduction number. Our results also suggest minimal pre-existing immunity to MERS-CoV in humans. The approach we describe can therefore provide crucial information about novel infections before serological surveys and other detailed analyses are available. The methods would also be applicable to data stratified by factors such as profession or location, which would make it possible to measure the transmission potential of emerging infections in a wide range of settings.",2015 Apr 10,"['Kucharski, Adam J.', 'Edmunds, W. John']",PLoS Comput Biol,,,False
6858a81e65c28599c9e674b9b8aa77ab11b79fad,PMC,3D Structure Prediction of Human β1-Adrenergic Receptor via Threading-Based Homology Modeling for Implications in Structure-Based Drug Designing,http://dx.doi.org/10.1371/journal.pone.0122223,PMC4393300,25860348,CC BY,"Dilated cardiomyopathy is a disease of left ventricular dysfunction accompanied by impairment of the β(1)-adrenergic receptor (β(1)-AR) signal cascade. The disturbed β(1)-AR function may be based on an elevated sympathetic tone observed in patients with heart failure. Prolonged adrenergic stimulation may induce metabolic and electrophysiological disturbances in the myocardium, resulting in tachyarrhythmia that leads to the development of heart failure in human and sudden death. Hence, β(1)-AR is considered as a promising drug target but attempts to develop effective and specific drug against this tempting pharmaceutical target is slowed down due to the lack of 3D structure of Homo sapiens β(1)-AR (hsβADR1). This study encompasses elucidation of 3D structural and physicochemical properties of hsβADR1 via threading-based homology modeling. Furthermore, the docking performance of several docking programs including Surflex-Dock, FRED, and GOLD were validated by re-docking and cross-docking experiments. GOLD and Surflex-Dock performed best in re-docking and cross docking experiments, respectively. Consequently, Surflex-Dock was used to predict the binding modes of four hsβADR1 agonists. This study provides clear understanding of hsβADR1 structure and its binding mechanism, thus help in providing the remedial solutions of cardiovascular, effective treatment of asthma and other diseases caused by malfunctioning of the target protein.",2015 Apr 10,"['Ul-Haq, Zaheer', 'Saeed, Maria', 'Halim, Sobia Ahsan', 'Khan, Waqasuddin']",PLoS One,,,True
5dee0488f20951e191da1c58d425a28eda883f49,PMC,A Bibliometric Analysis of Publications on Pluripotent Stem Cell Research,,PMC4393672,25870835,CC BY,"OBJECTIVE: Human pluripotent stem cells are self-renewing cells with the ability to differentiate into a variety of cells and are viewed to have great potential in the field of regenerative medicine. Research in pluripotent stem cells holds great promise for patient specific therapy in various diseases. In this study, pluripotent stem cell articles published from 1991 to 2012 were screened and retrieved from Science Citation Index Expanded (SCI-EXPANDED). MATERIALS AND METHODS: In this retrospective study, the publication trend, citation trends for top articles, distributions of journals and Web of Science categories were analyzed. Five bibliometric indicators including total articles, independent articles, collaborative articles, first author articles, and corresponding author articles were applied to compare publications between countries and institutions. RESULTS: The impact of top articles changed from year to year. Top cited articles in previous publication years were not the same as recent years. ""Induced pluripotent stem cell (s)"" and ""embryonic stem cell (s)"" were the most used author keywords in pluripotent stem cell research. In addition, the winner of the Nobel Prize in physiology or medicine in 2012, Prof. Shinya Yamanaka, published four of the top ten most frequently cited articles. CONCLUSION: The comprehensive analysis of highly cited articles in the stem cell field could identify milestones and important contributors, giving a historic perspective on scientific progress.",2015 Apr 8 Spring,"['Lin, Changshuan L.', 'Ho, Yuh-Shan']",Cell J,,,True
d760a0c49650a6c2a3d822bab4417057e6be1cd1,PMC,"Correction: Xie, H.; et al. 3D QSAR Studies, Pharmacophore Modeling and Virtual Screening on a Series of Steroidal Aromatase Inhibitors. Int. J. Mol. Sci. 2014, 15, 20927–20947",http://dx.doi.org/10.3390/ijms16035072,PMC4394465,25751723,CC BY,,2015 Mar 5,"['Xie, Huiding', 'Qiu, Kaixiong', 'Xie, Xiaoguang']",Int J Mol Sci,,,True
0b1af480d35b739da799df76a25463bc2ee4bbe5,PMC,The pbrB Gene Encodes a Laccase Required for DHN-Melanin Synthesis in Conidia of Talaromyces (Penicillium) marneffei,http://dx.doi.org/10.1371/journal.pone.0122728,PMC4395095,25866870,CC BY,"Talaromyces marneffei (Basionym: Penicillium marneffei) is a significant opportunistic fungal pathogen in patients infected with human immunodeficiency virus in Southeast Asia. T. marneffei cells have been shown to become melanized in vivo. Melanins are pigment biopolymers which act as a non-specific protectant against various stressors and which play an important role during virulence in fungi. The synthesis of the two most commonly found melanins in fungi, the eumelanin DOPA-melanin and the allomelanin DHN-melanin, requires the action of laccase enzymes. The T. marneffei genome encodes a number of laccases and this study describes the characterization of one of these, pbrB, during growth and development. A strain carrying a PbrB-GFP fusion shows that pbrB is expressed at high levels during asexual development (conidiation) but not in cells growing vegetatively. The pbrB gene is required for the synthesis of DHN-melanin in conidia and when deleted results in brown pigmented conidia, in contrast to the green conidia of the wild type.",2015 Apr 13,"['Sapmak, Ariya', 'Boyce, Kylie J.', 'Andrianopoulos, Alex', 'Vanittanakom, Nongnuch']",PLoS One,,,True
28f89ac0fa6a72cf3dc315817c2e670c10dec347,PMC,Hepatitis C Virus RNA Replication Depends on Specific Cis- and Trans-Acting Activities of Viral Nonstructural Proteins,http://dx.doi.org/10.1371/journal.ppat.1004817,PMC4395149,25875808,CC BY,"Many positive-strand RNA viruses encode genes that can function in trans, whereas other genes are required in cis for genome replication. The mechanisms underlying trans- and cis-preferences are not fully understood. Here, we evaluate this concept for hepatitis C virus (HCV), an important cause of chronic liver disease and member of the Flaviviridae family. HCV encodes five nonstructural (NS) genes that are required for RNA replication. To date, only two of these genes, NS4B and NS5A, have been trans-complemented, leading to suggestions that other replicase genes work only in cis. We describe a new quantitative system to measure the cis- and trans-requirements for HCV NS gene function in RNA replication and identify several lethal mutations in the NS3, NS4A, NS4B, NS5A, and NS5B genes that can be complemented in trans, alone or in combination, by expressing the NS3–5B polyprotein from a synthetic mRNA. Although NS5B RNA binding and polymerase activities can be supplied in trans, NS5B protein expression was required in cis, indicating that NS5B has a cis-acting role in replicase assembly distinct from its known enzymatic activity. Furthermore, the RNA binding and NTPase activities of the NS3 helicase domain were required in cis, suggesting that these activities play an essential role in RNA template selection. A comprehensive complementation group analysis revealed functional linkages between NS3-4A and NS4B and between NS5B and the upstream NS3–5A genes. Finally, NS5B polymerase activity segregated with a daclatasvir-sensitive NS5A activity, which could explain the synergy of this antiviral compound with nucleoside analogs in patients. Together, these studies define several new aspects of HCV replicase structure-function, help to explain the potency of HCV-specific combination therapies, and provide an experimental framework for the study of cis- and trans-acting activities in positive-strand RNA virus replication more generally.",2015 Apr 13,"['Kazakov, Teymur', 'Yang, Feng', 'Ramanathan, Harish N.', 'Kohlway, Andrew', 'Diamond, Michael S.', 'Lindenbach, Brett D.']",PLoS Pathog,,,True
13098fe624915ac71c984fbe7fe0c0a2546c66de,PMC,Hepatitis C Virus RNA Replication Depends on Specific Cis- and Trans-Acting Activities of Viral Nonstructural Proteins,http://dx.doi.org/10.1371/journal.ppat.1004817,PMC4395149,25875808,CC BY,"Many positive-strand RNA viruses encode genes that can function in trans, whereas other genes are required in cis for genome replication. The mechanisms underlying trans- and cis-preferences are not fully understood. Here, we evaluate this concept for hepatitis C virus (HCV), an important cause of chronic liver disease and member of the Flaviviridae family. HCV encodes five nonstructural (NS) genes that are required for RNA replication. To date, only two of these genes, NS4B and NS5A, have been trans-complemented, leading to suggestions that other replicase genes work only in cis. We describe a new quantitative system to measure the cis- and trans-requirements for HCV NS gene function in RNA replication and identify several lethal mutations in the NS3, NS4A, NS4B, NS5A, and NS5B genes that can be complemented in trans, alone or in combination, by expressing the NS3–5B polyprotein from a synthetic mRNA. Although NS5B RNA binding and polymerase activities can be supplied in trans, NS5B protein expression was required in cis, indicating that NS5B has a cis-acting role in replicase assembly distinct from its known enzymatic activity. Furthermore, the RNA binding and NTPase activities of the NS3 helicase domain were required in cis, suggesting that these activities play an essential role in RNA template selection. A comprehensive complementation group analysis revealed functional linkages between NS3-4A and NS4B and between NS5B and the upstream NS3–5A genes. Finally, NS5B polymerase activity segregated with a daclatasvir-sensitive NS5A activity, which could explain the synergy of this antiviral compound with nucleoside analogs in patients. Together, these studies define several new aspects of HCV replicase structure-function, help to explain the potency of HCV-specific combination therapies, and provide an experimental framework for the study of cis- and trans-acting activities in positive-strand RNA virus replication more generally.",2015 Apr 13,"['Kazakov, Teymur', 'Yang, Feng', 'Ramanathan, Harish N.', 'Kohlway, Andrew', 'Diamond, Michael S.', 'Lindenbach, Brett D.']",PLoS Pathog,,,False
61c1c4f195894c17cc2ce3caaa2d8cd617e7b892,PMC,Hepatitis C Virus RNA Replication Depends on Specific Cis- and Trans-Acting Activities of Viral Nonstructural Proteins,http://dx.doi.org/10.1371/journal.ppat.1004817,PMC4395149,25875808,CC BY,"Many positive-strand RNA viruses encode genes that can function in trans, whereas other genes are required in cis for genome replication. The mechanisms underlying trans- and cis-preferences are not fully understood. Here, we evaluate this concept for hepatitis C virus (HCV), an important cause of chronic liver disease and member of the Flaviviridae family. HCV encodes five nonstructural (NS) genes that are required for RNA replication. To date, only two of these genes, NS4B and NS5A, have been trans-complemented, leading to suggestions that other replicase genes work only in cis. We describe a new quantitative system to measure the cis- and trans-requirements for HCV NS gene function in RNA replication and identify several lethal mutations in the NS3, NS4A, NS4B, NS5A, and NS5B genes that can be complemented in trans, alone or in combination, by expressing the NS3–5B polyprotein from a synthetic mRNA. Although NS5B RNA binding and polymerase activities can be supplied in trans, NS5B protein expression was required in cis, indicating that NS5B has a cis-acting role in replicase assembly distinct from its known enzymatic activity. Furthermore, the RNA binding and NTPase activities of the NS3 helicase domain were required in cis, suggesting that these activities play an essential role in RNA template selection. A comprehensive complementation group analysis revealed functional linkages between NS3-4A and NS4B and between NS5B and the upstream NS3–5A genes. Finally, NS5B polymerase activity segregated with a daclatasvir-sensitive NS5A activity, which could explain the synergy of this antiviral compound with nucleoside analogs in patients. Together, these studies define several new aspects of HCV replicase structure-function, help to explain the potency of HCV-specific combination therapies, and provide an experimental framework for the study of cis- and trans-acting activities in positive-strand RNA virus replication more generally.",2015 Apr 13,"['Kazakov, Teymur', 'Yang, Feng', 'Ramanathan, Harish N.', 'Kohlway, Andrew', 'Diamond, Michael S.', 'Lindenbach, Brett D.']",PLoS Pathog,,,False
05e124c390d75f96fe992f78021c146b450563bf,PMC,Hepatitis C Virus RNA Replication Depends on Specific Cis- and Trans-Acting Activities of Viral Nonstructural Proteins,http://dx.doi.org/10.1371/journal.ppat.1004817,PMC4395149,25875808,CC BY,"Many positive-strand RNA viruses encode genes that can function in trans, whereas other genes are required in cis for genome replication. The mechanisms underlying trans- and cis-preferences are not fully understood. Here, we evaluate this concept for hepatitis C virus (HCV), an important cause of chronic liver disease and member of the Flaviviridae family. HCV encodes five nonstructural (NS) genes that are required for RNA replication. To date, only two of these genes, NS4B and NS5A, have been trans-complemented, leading to suggestions that other replicase genes work only in cis. We describe a new quantitative system to measure the cis- and trans-requirements for HCV NS gene function in RNA replication and identify several lethal mutations in the NS3, NS4A, NS4B, NS5A, and NS5B genes that can be complemented in trans, alone or in combination, by expressing the NS3–5B polyprotein from a synthetic mRNA. Although NS5B RNA binding and polymerase activities can be supplied in trans, NS5B protein expression was required in cis, indicating that NS5B has a cis-acting role in replicase assembly distinct from its known enzymatic activity. Furthermore, the RNA binding and NTPase activities of the NS3 helicase domain were required in cis, suggesting that these activities play an essential role in RNA template selection. A comprehensive complementation group analysis revealed functional linkages between NS3-4A and NS4B and between NS5B and the upstream NS3–5A genes. Finally, NS5B polymerase activity segregated with a daclatasvir-sensitive NS5A activity, which could explain the synergy of this antiviral compound with nucleoside analogs in patients. Together, these studies define several new aspects of HCV replicase structure-function, help to explain the potency of HCV-specific combination therapies, and provide an experimental framework for the study of cis- and trans-acting activities in positive-strand RNA virus replication more generally.",2015 Apr 13,"['Kazakov, Teymur', 'Yang, Feng', 'Ramanathan, Harish N.', 'Kohlway, Andrew', 'Diamond, Michael S.', 'Lindenbach, Brett D.']",PLoS Pathog,,,False
b70dc2c0352fbfd55b26b7d9548fad4867476948,PMC,Hepatitis C Virus RNA Replication Depends on Specific Cis- and Trans-Acting Activities of Viral Nonstructural Proteins,http://dx.doi.org/10.1371/journal.ppat.1004817,PMC4395149,25875808,CC BY,"Many positive-strand RNA viruses encode genes that can function in trans, whereas other genes are required in cis for genome replication. The mechanisms underlying trans- and cis-preferences are not fully understood. Here, we evaluate this concept for hepatitis C virus (HCV), an important cause of chronic liver disease and member of the Flaviviridae family. HCV encodes five nonstructural (NS) genes that are required for RNA replication. To date, only two of these genes, NS4B and NS5A, have been trans-complemented, leading to suggestions that other replicase genes work only in cis. We describe a new quantitative system to measure the cis- and trans-requirements for HCV NS gene function in RNA replication and identify several lethal mutations in the NS3, NS4A, NS4B, NS5A, and NS5B genes that can be complemented in trans, alone or in combination, by expressing the NS3–5B polyprotein from a synthetic mRNA. Although NS5B RNA binding and polymerase activities can be supplied in trans, NS5B protein expression was required in cis, indicating that NS5B has a cis-acting role in replicase assembly distinct from its known enzymatic activity. Furthermore, the RNA binding and NTPase activities of the NS3 helicase domain were required in cis, suggesting that these activities play an essential role in RNA template selection. A comprehensive complementation group analysis revealed functional linkages between NS3-4A and NS4B and between NS5B and the upstream NS3–5A genes. Finally, NS5B polymerase activity segregated with a daclatasvir-sensitive NS5A activity, which could explain the synergy of this antiviral compound with nucleoside analogs in patients. Together, these studies define several new aspects of HCV replicase structure-function, help to explain the potency of HCV-specific combination therapies, and provide an experimental framework for the study of cis- and trans-acting activities in positive-strand RNA virus replication more generally.",2015 Apr 13,"['Kazakov, Teymur', 'Yang, Feng', 'Ramanathan, Harish N.', 'Kohlway, Andrew', 'Diamond, Michael S.', 'Lindenbach, Brett D.']",PLoS Pathog,,,False
1951545d70e8568083cde219d2583c1aae0c4061,PMC,"Factors responsible for the emergence of arboviruses; strategies, challenges and limitations for their control",http://dx.doi.org/10.1038/emi.2015.18,PMC4395659,26038768,CC BY,"Slave trading of Africans to the Americas, during the 16th to the 19th century was responsible for the first recorded emergence in the New World of two arthropod-borne viruses (arboviruses), yellow fever virus and dengue virus. Many other arboviruses have since emerged from their sylvatic reservoirs and dispersed globally due to evolving factors that include anthropological behaviour, commercial transportation and land-remediation. Here, we outline some characteristics of these highly divergent arboviruses, including the variety of life cycles they have developed and the mechanisms by which they have adapted to evolving changes in habitat and host availability. We cite recent examples of virus emergence that exemplify how arboviruses have exploited the consequences of the modern human lifestyle. Using our current understanding of these viruses, we also attempt to demonstrate some of the limitations encountered in developing control strategies to reduce the impact of future emerging arbovirus diseases. Finally, we present recommendations for development by an international panel of experts reporting directly to World Health Organization, with the intention of providing internationally acceptable guidelines for improving emerging arbovirus disease control strategies. Success in these aims should alleviate the suffering and costs encountered during recent decades when arboviruses have emerged from their sylvatic environment.",2015 Mar 25,"['Liang, Guodong', 'Gao, Xiaoyan', 'Gould, Ernest A']",Emerg Microbes Infect,,,True
27b984da31424966ac5c45002fb7788bcf2f8a24,PMC,Cationic nanoparticles directly bind angiotensin-converting enzyme 2 and induce acute lung injury in mice,http://dx.doi.org/10.1186/s12989-015-0080-x,PMC4395934,25890286,CC BY,"BACKGROUND: Nanoparticles have become a key technology in multiple industries. However, there are growing reports of the toxicity of nanomaterials to humans. In particular, nanomaterials have been linked to lung diseases. The molecular mechanisms of nanoparticle toxicity are largely unexplored. METHODS: Acute lung injury was induced in wild-type mice and angiotensin-coverting enzyme 2 (ACE2) knockout mice by the intratracheal instillation of cationic polyamidoamine dendrimer (PAMAM) nanoparticles. For rescue experiments, losartan (15 mg/kg in PBS) was injected intraperitoneally 30 min before nanoparticle administration. RESULTS: Some PAMAM nanoparticles, but not anionic PAMAM nanoparticles or carbon nanotubes, triggered acute lung failure in mice. Mechanistically, cationic nanoparticles can directly bind ACE2, decrease its activity and down-regulate its expression level in lung tissue, resulting in deregulation of the renin-angiotensin system. Gene inactivation of Ace2 can exacerbate lung injury. Importantly, the administration of losartan, which is an angiotensin II type I receptor antagonist, can ameliorate PAMAM nanoparticle-induced lung injury. CONCLUSIONS: Our data provide molecular insight into PAMAM nanoparticle-induced lung injury and suggest potential therapeutic and screening strategies to address the safety of nanomaterials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-015-0080-x) contains supplementary material, which is available to authorized users.",2015 Mar 7,"['Sun, Yang', 'Guo, Feng', 'Zou, Zhen', 'Li, Chenggang', 'Hong, Xiaoxu', 'Zhao, Yan', 'Wang, Chenxuan', 'Wang, Hongliang', 'Liu, Haolin', 'Yang, Peng', 'Han, Zongsheng', 'Liu, Kangtai', 'Kuba, Keiji', 'Song, Bin', 'Gao, Jinming', 'Mo, Ziyao', 'Li, Dangsheng', 'Li, Bo', 'Li, Qihan', 'Zhong, Nanshan', 'Wang, Chen', 'Penninger, Josef M', 'Jiang, Chengyu']",Part Fibre Toxicol,,,False
e8b1ea3e506278ac9a195929ec4a8fb1801c4a86,PMC,Cationic nanoparticles directly bind angiotensin-converting enzyme 2 and induce acute lung injury in mice,http://dx.doi.org/10.1186/s12989-015-0080-x,PMC4395934,25890286,CC BY,"BACKGROUND: Nanoparticles have become a key technology in multiple industries. However, there are growing reports of the toxicity of nanomaterials to humans. In particular, nanomaterials have been linked to lung diseases. The molecular mechanisms of nanoparticle toxicity are largely unexplored. METHODS: Acute lung injury was induced in wild-type mice and angiotensin-coverting enzyme 2 (ACE2) knockout mice by the intratracheal instillation of cationic polyamidoamine dendrimer (PAMAM) nanoparticles. For rescue experiments, losartan (15 mg/kg in PBS) was injected intraperitoneally 30 min before nanoparticle administration. RESULTS: Some PAMAM nanoparticles, but not anionic PAMAM nanoparticles or carbon nanotubes, triggered acute lung failure in mice. Mechanistically, cationic nanoparticles can directly bind ACE2, decrease its activity and down-regulate its expression level in lung tissue, resulting in deregulation of the renin-angiotensin system. Gene inactivation of Ace2 can exacerbate lung injury. Importantly, the administration of losartan, which is an angiotensin II type I receptor antagonist, can ameliorate PAMAM nanoparticle-induced lung injury. CONCLUSIONS: Our data provide molecular insight into PAMAM nanoparticle-induced lung injury and suggest potential therapeutic and screening strategies to address the safety of nanomaterials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-015-0080-x) contains supplementary material, which is available to authorized users.",2015 Mar 7,"['Sun, Yang', 'Guo, Feng', 'Zou, Zhen', 'Li, Chenggang', 'Hong, Xiaoxu', 'Zhao, Yan', 'Wang, Chenxuan', 'Wang, Hongliang', 'Liu, Haolin', 'Yang, Peng', 'Han, Zongsheng', 'Liu, Kangtai', 'Kuba, Keiji', 'Song, Bin', 'Gao, Jinming', 'Mo, Ziyao', 'Li, Dangsheng', 'Li, Bo', 'Li, Qihan', 'Zhong, Nanshan', 'Wang, Chen', 'Penninger, Josef M', 'Jiang, Chengyu']",Part Fibre Toxicol,,,False
43c6dfd539d037ea096725addf62cad445e88959,PMC,Cationic nanoparticles directly bind angiotensin-converting enzyme 2 and induce acute lung injury in mice,http://dx.doi.org/10.1186/s12989-015-0080-x,PMC4395934,25890286,CC BY,"BACKGROUND: Nanoparticles have become a key technology in multiple industries. However, there are growing reports of the toxicity of nanomaterials to humans. In particular, nanomaterials have been linked to lung diseases. The molecular mechanisms of nanoparticle toxicity are largely unexplored. METHODS: Acute lung injury was induced in wild-type mice and angiotensin-coverting enzyme 2 (ACE2) knockout mice by the intratracheal instillation of cationic polyamidoamine dendrimer (PAMAM) nanoparticles. For rescue experiments, losartan (15 mg/kg in PBS) was injected intraperitoneally 30 min before nanoparticle administration. RESULTS: Some PAMAM nanoparticles, but not anionic PAMAM nanoparticles or carbon nanotubes, triggered acute lung failure in mice. Mechanistically, cationic nanoparticles can directly bind ACE2, decrease its activity and down-regulate its expression level in lung tissue, resulting in deregulation of the renin-angiotensin system. Gene inactivation of Ace2 can exacerbate lung injury. Importantly, the administration of losartan, which is an angiotensin II type I receptor antagonist, can ameliorate PAMAM nanoparticle-induced lung injury. CONCLUSIONS: Our data provide molecular insight into PAMAM nanoparticle-induced lung injury and suggest potential therapeutic and screening strategies to address the safety of nanomaterials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-015-0080-x) contains supplementary material, which is available to authorized users.",2015 Mar 7,"['Sun, Yang', 'Guo, Feng', 'Zou, Zhen', 'Li, Chenggang', 'Hong, Xiaoxu', 'Zhao, Yan', 'Wang, Chenxuan', 'Wang, Hongliang', 'Liu, Haolin', 'Yang, Peng', 'Han, Zongsheng', 'Liu, Kangtai', 'Kuba, Keiji', 'Song, Bin', 'Gao, Jinming', 'Mo, Ziyao', 'Li, Dangsheng', 'Li, Bo', 'Li, Qihan', 'Zhong, Nanshan', 'Wang, Chen', 'Penninger, Josef M', 'Jiang, Chengyu']",Part Fibre Toxicol,,,False
fd60728329125d9577016c256ad2bcd69240ac21,PMC,Cationic nanoparticles directly bind angiotensin-converting enzyme 2 and induce acute lung injury in mice,http://dx.doi.org/10.1186/s12989-015-0080-x,PMC4395934,25890286,CC BY,"BACKGROUND: Nanoparticles have become a key technology in multiple industries. However, there are growing reports of the toxicity of nanomaterials to humans. In particular, nanomaterials have been linked to lung diseases. The molecular mechanisms of nanoparticle toxicity are largely unexplored. METHODS: Acute lung injury was induced in wild-type mice and angiotensin-coverting enzyme 2 (ACE2) knockout mice by the intratracheal instillation of cationic polyamidoamine dendrimer (PAMAM) nanoparticles. For rescue experiments, losartan (15 mg/kg in PBS) was injected intraperitoneally 30 min before nanoparticle administration. RESULTS: Some PAMAM nanoparticles, but not anionic PAMAM nanoparticles or carbon nanotubes, triggered acute lung failure in mice. Mechanistically, cationic nanoparticles can directly bind ACE2, decrease its activity and down-regulate its expression level in lung tissue, resulting in deregulation of the renin-angiotensin system. Gene inactivation of Ace2 can exacerbate lung injury. Importantly, the administration of losartan, which is an angiotensin II type I receptor antagonist, can ameliorate PAMAM nanoparticle-induced lung injury. CONCLUSIONS: Our data provide molecular insight into PAMAM nanoparticle-induced lung injury and suggest potential therapeutic and screening strategies to address the safety of nanomaterials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-015-0080-x) contains supplementary material, which is available to authorized users.",2015 Mar 7,"['Sun, Yang', 'Guo, Feng', 'Zou, Zhen', 'Li, Chenggang', 'Hong, Xiaoxu', 'Zhao, Yan', 'Wang, Chenxuan', 'Wang, Hongliang', 'Liu, Haolin', 'Yang, Peng', 'Han, Zongsheng', 'Liu, Kangtai', 'Kuba, Keiji', 'Song, Bin', 'Gao, Jinming', 'Mo, Ziyao', 'Li, Dangsheng', 'Li, Bo', 'Li, Qihan', 'Zhong, Nanshan', 'Wang, Chen', 'Penninger, Josef M', 'Jiang, Chengyu']",Part Fibre Toxicol,,,False
1b42f78eee63e2f5c5a58a59759dc119ef1f73da,PMC,Cationic nanoparticles directly bind angiotensin-converting enzyme 2 and induce acute lung injury in mice,http://dx.doi.org/10.1186/s12989-015-0080-x,PMC4395934,25890286,CC BY,"BACKGROUND: Nanoparticles have become a key technology in multiple industries. However, there are growing reports of the toxicity of nanomaterials to humans. In particular, nanomaterials have been linked to lung diseases. The molecular mechanisms of nanoparticle toxicity are largely unexplored. METHODS: Acute lung injury was induced in wild-type mice and angiotensin-coverting enzyme 2 (ACE2) knockout mice by the intratracheal instillation of cationic polyamidoamine dendrimer (PAMAM) nanoparticles. For rescue experiments, losartan (15 mg/kg in PBS) was injected intraperitoneally 30 min before nanoparticle administration. RESULTS: Some PAMAM nanoparticles, but not anionic PAMAM nanoparticles or carbon nanotubes, triggered acute lung failure in mice. Mechanistically, cationic nanoparticles can directly bind ACE2, decrease its activity and down-regulate its expression level in lung tissue, resulting in deregulation of the renin-angiotensin system. Gene inactivation of Ace2 can exacerbate lung injury. Importantly, the administration of losartan, which is an angiotensin II type I receptor antagonist, can ameliorate PAMAM nanoparticle-induced lung injury. CONCLUSIONS: Our data provide molecular insight into PAMAM nanoparticle-induced lung injury and suggest potential therapeutic and screening strategies to address the safety of nanomaterials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-015-0080-x) contains supplementary material, which is available to authorized users.",2015 Mar 7,"['Sun, Yang', 'Guo, Feng', 'Zou, Zhen', 'Li, Chenggang', 'Hong, Xiaoxu', 'Zhao, Yan', 'Wang, Chenxuan', 'Wang, Hongliang', 'Liu, Haolin', 'Yang, Peng', 'Han, Zongsheng', 'Liu, Kangtai', 'Kuba, Keiji', 'Song, Bin', 'Gao, Jinming', 'Mo, Ziyao', 'Li, Dangsheng', 'Li, Bo', 'Li, Qihan', 'Zhong, Nanshan', 'Wang, Chen', 'Penninger, Josef M', 'Jiang, Chengyu']",Part Fibre Toxicol,,,True
424d6c622643d36a7f8d9a1d2714f4cef49387ed,PMC,"1,2,3,4,6-Penta-O-galloylglucose within Galla Chinensis Inhibits Human LDH-A and Attenuates Cell Proliferation in MDA-MB-231 Breast Cancer Cells",http://dx.doi.org/10.1155/2015/276946,PMC4396556,25918543,CC BY,"A characteristic feature of aggressive malignancy is the overexpression of lactic acid dehydrogenase- (LDH-) A, concomitant to pericellular accumulation of lactate. In a recent high-throughput screening, we identified Rhus chinensis (Mill.) gallnut (RCG) (also known as Galla Chinensis) extract as a potent (IC(50) < 1 µg/mL) inhibitor of human LDH-A (hLDH-A). In this study, through bioactivity guided fractionation of the crude extract, the data demonstrate that penta-1,2,3,4,6-O-galloyl-β-D-glucose (PGG) was a primary constituent responsible for hLDH-A inhibition, present at ~9.95 ± 0.34% dry weight. Theoretical molecular docking studies of hLDH-A indicate that PGG acts through competitive binding at the NADH cofactor site, effects confirmed by functional enzyme studies where the IC(50) = 27.32 nM was reversed with increasing concentration of NADH. Moreover, we confirm protein expression of hLDH-A in MDA-231 human breast carcinoma cells and show that PGG was toxic (LC(50) = 94.18 µM), parallel to attenuated lactic acid production (IC(50) = 97.81 µM). In a 72-hour cell proliferation assay, PGG was found to be a potent cytostatic agent with ability to halt cell division (IC(50) = 1.2 µM) relative to paclitaxel (IC(50) < 100 nM). In summary, these findings demonstrate that PGG is a potent hLDH-A inhibitor with significant capacity to halt proliferation of human breast cancer cells.",2015 Mar 30,"['Deiab, Shihab', 'Mazzio, Elizabeth', 'Eyunni, Suresh', 'McTier, Oshlii', 'Mateeva, Nelly', 'Elshami, Faisel', 'Soliman, Karam F. A.']",Evid Based Complement Alternat Med,,,True
eaaa5939391fb99e06e8d6b8723e6b061632b1c3,PMC,Selection of key recommendations for quality indicators describing good quality outbreak response,http://dx.doi.org/10.1186/s12879-015-0896-x,PMC4397715,25888491,CC BY,"BACKGROUND: The performance of recommended control measures is necessary for quick and uniform infectious disease outbreak control. To assess whether these procedures are performed, a valid set of quality indicators (QIs) is required. The goal of this study was to select a set of key recommendations that can be systematically translated into QIs to measure the quality of infectious disease outbreak response from the perspective of disaster emergency responders and infectious disease control professionals. METHODS: Applying the Rand modified Delphi procedure, the following steps were taken to systematically select a set of key recommendations: extraction of recommendations from relevant literature; appraisal of the recommendations in terms of relevance through questionnaires to experts; expert meeting to discuss recommendations; prioritization of recommendations through a second questionnaire; and final expert meeting to approve the selected set. Infectious disease physicians and nurses, policymakers and communication experts participated in the expert group (n = 48). RESULTS: In total, 54 national and international publications were systematically searched for recommendations, yielding over 200 recommendations. The Rand modified Delphi procedure resulted in a set of 65 key recommendations. The key recommendations were categorized into 10 domains describing the whole response pathway from outbreak recognition to aftercare. CONCLUSION: This study provides a set of key recommendations that represents ‘good quality of response to an infectious disease outbreak’. These key recommendations can be systematically translated into QIs. Organizations and professionals involved in outbreak control can use these QIs to monitor the quality of response to infectious disease outbreaks and to assess in which domains improvement is needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0896-x) contains supplementary material, which is available to authorized users.",2015 Mar 31,"['Belfroid, Evelien', 'LA Hautvast, Jeannine', 'Hilbink, Mirrian', 'Timen, Aura', 'Hulscher, Marlies EJL']",BMC Infect Dis,,,True
8a665903721dadcf01c1dd7476a7715709cee0ad,PMC,Outcomes of Early Administration of Cidofovir in Non-Immunocompromised Patients with Severe Adenovirus Pneumonia,http://dx.doi.org/10.1371/journal.pone.0122642,PMC4398328,25875735,CC BY,"The benefits of treatment with antiviral therapy for severe adenovirus (AdV) pneumonia are not well established. We described the clinical characteristics and treatment outcomes of early cidofovir treatment of severe AdV pneumonia in non-immunocompromised patients. We retrospectively reviewed the medical records of all patients diagnosed with severe AdV pneumonia between 2012 and 2014. A total of seven non-immunocompromised patients with severe AdV pneumonia were identified, and all isolates typed (n = 6) were human AdV-B55. All patients had progressive respiratory failure with lobar consolidation with or without patchy ground glass opacity. Three patients required vasopressors and mechanical ventilation. All patients had abnormal laboratory findings including: leukopenia, thrombocytopenia, or elevated liver enzymes. After admission, all patients received antiviral therapy with cidofovir, and the median time from admission to cidofovir administration was 48 h and median the time from onset of symptoms to cidofovir administration was 7.1 days. After cidofovir administration, complete symptomatic improvement occurred after a median of 12 days and radiographic resolution occurred after a median of 21 days. Consequently, all patients completely improved without complications. Our data suggest that early administration of cidofovir in the course of treatment for respiratory failure as a result of AdV pneumonia in non-immunocompromised patients could be a treatment strategy worth considering, especially in cases of HAdV-55 infection.",2015 Apr 15,"['Kim, Se Jin', 'Kim, Kang', 'Park, Sung Bum', 'Hong, Duck Jin', 'Jhun, Byung Woo']",PLoS One,,,True
fed1fd6ad6a0fff6d3532a8b13f12f25347928b7,PMC,Social Capital and Health-Protective Behavior Intentions in an Influenza Pandemic,http://dx.doi.org/10.1371/journal.pone.0122970,PMC4398366,25874625,CC BY,"Health-protective behaviors, such as receiving a vaccine, wearing a face mask, and washing hands frequently, can reduce the risk of contracting influenza. However, little is known about how social capital may influence health-protective behavior in the general population. This study examined whether each of the social capital dimensions (bonding, bridging, and linking) contributed to the intention to adopt any of the health-protective behaviors in an influenza pandemic. The data of this study were from the 2014 Taiwan Social Change Survey. A stratified, three-stage probability proportional-to-size sampling from across the nation, was conducted to select adults aged 20 years and older (N = 1,745). Bonding social capital was measured by the frequency of neighborly contact and support. Bridging social capital was measured based on association membership. Linking social capital was measured according to general government trust and trust in the government’s capacity to counter an influenza pandemic. Binary logistic regressions were used to assess the multivariate associations between social capital and behavioral intention. The study results indicate that social capital may influence the response to influenza pandemic. Specifically, the intention to receive a vaccine and to wash hands more frequently were associated with the linking dimension and the bonding dimension of social capital, while the intention to wear a face mask was associated with all forms of social capital. The findings of this study suggest that government credibility and interpersonal networks may play a crucial role in health-protective behavior. This study provides new insights into how to improve the effectiveness of influenza prevention campaigns.",2015 Apr 15,"['Chuang, Ying-Chih', 'Huang, Ya-Li', 'Tseng, Kuo-Chien', 'Yen, Chia-Hsin', 'Yang, Lin-hui']",PLoS One,,,True
886c69ba9b7fb6441b3dc9c06d77abf30e3a0703,PMC,The UPR Branch IRE1-bZIP60 in Plants Plays an Essential Role in Viral Infection and Is Complementary to the Only UPR Pathway in Yeast,http://dx.doi.org/10.1371/journal.pgen.1005164,PMC4398384,25875739,CC BY,"The unfolded protein response (UPR) signaling network encompasses two pathways in plants, one mediated by inositol-requiring protein-1 (IRE1)-bZIP60 mRNA and the other by site-1/site-2 proteases (S1P/S2P)-bZIP17/bZIP28. As the major sensor of UPR in eukaryotes, IRE1, in response to endoplasmic reticulum (ER) stress, catalyzes the unconventional splicing of HAC1 in yeast, bZIP60 in plants and XBP1 in metazoans. Recent studies suggest that IRE1p and HAC1 mRNA, the only UPR pathway found in yeast, evolves as a cognate system responsible for the robust UPR induction. However, the functional connectivity of IRE1 and its splicing target in multicellular eukaryotes as well as the degree of conservation of IRE1 downstream signaling effectors across eukaryotes remains to be established. Here, we report that IRE1 and its substrate bZIP60 function as a strictly cognate enzyme-substrate pair to control viral pathogenesis in plants. Moreover, we show that the S1P/S2P-bZIP17/bZIP28 pathway, the other known branch of UPR in plants, does not play a detectable role in virus infection, demonstrating the distinct function of the IRE1-bZIP60 pathway in plants. Furthermore, we provide evidence that bZIP60 and HAC1, products of the enzyme-substrate duet, rather than IRE1, are functionally replaceable to cope with ER stress in yeast. Taken together, we conclude that the downstream signaling of the IRE1-mediated splicing is evolutionarily conserved in yeast and plants, and that the IRE1-bZIP60 UPR pathway not only confers overlapping functions with the other UPR branch in fundamental biology but also may exert a unique role in certain biological processes such as virus-plant interactions.",2015 Apr 15,"['Zhang, Lingrui', 'Chen, Hui', 'Brandizzi, Federica', 'Verchot, Jeanmarie', 'Wang, Aiming']",PLoS Genet,,,True
ad00ba859cb901a728e33191c4795084743cb986,PMC,"Early Detection for Cases of Enterovirus- and Influenza-Like Illness through a Newly Established School-Based Syndromic Surveillance System in Taipei, January 2010 ~ August 2011",http://dx.doi.org/10.1371/journal.pone.0122865,PMC4398411,25875080,CC BY,"School children may transmit pathogens with cluster cases occurring on campuses and in families. In response to the 2009 influenza A (H1N1) pandemic, Taipei City Government officials developed a School-based Infectious Disease Syndromic Surveillance System (SID-SSS). Teachers and nurses from preschools to universities in all 12 districts within Taipei are required to daily report cases of symptomatic children or sick leave requests through the SID-SSS. The pre-diagnosis at schools is submitted firstly as common pediatric disease syndrome-groups and re-submitted after confirmation by physicians. We retrieved these data from January 2010 to August 2011 for spatio-temporal analysis and evaluated the temporal trends with cases obtained from both the Emergency Department-based Syndromic Surveillance System (ED-SSS) and the Longitudinal Health Insurance Database 2005 (LHID2005). Through the SID-SSS, enterovirus-like illness (EVI) and influenza-like illness (ILI) were the two most reported syndrome groups (77.6% and 15.8% among a total of 19,334 cases, respectively). The pre-diagnosis judgments made by school teachers and nurses showed high consistency with physicians’ clinical diagnoses for EVI (97.8%) and ILI (98.9%). Most importantly, the SID-SSS had better timeliness with earlier peaks of EVI and ILI than those in the ED-SSS. Furthermore, both of the syndrome groups in these two surveillance systems had the best correlation reaching 0.98 and 0.95, respectively (p<0.01). Spatio-temporal analysis observed the patterns of EVI and ILI both diffuse from the northern suburban districts to central Taipei, with ILI spreading faster. This novel system can identify early suspected cases of two important pediatric infections occurring at schools, and clusters from schools/families. It was also cost-effective (95.5% of the operation cost reduced and 59.7% processing time saved). The timely surveillance of mild EVI and ILI cases integrated with spatial analysis may help public health decision-makers with where to target for enhancing surveillance and prevention measures to minimize severe cases.",2015 Apr 15,"['Weng, Ting Chia', 'Chan, Ta Chien', 'Lin, Hsien Tang', 'Chang, Chia Kun Jasper', 'Wang, Wen Wen', 'Li, Zheng Rong Tiger', 'Cheng, Hao-Yuan', 'Chu, Yu-Roo', 'Chiu, Allen Wen-Hsiang', 'Yen, Muh-Yong', 'King, Chwan-Chuen']",PLoS One,,,True
06989a9659f1b9b10abc5b92a90ecff38a778d55,PMC,Identification of a Novel Afipia Species Isolated from an Indian Flying Fox,http://dx.doi.org/10.1371/journal.pone.0121274,PMC4398416,25874801,CC BY,"An old world fruit bat Pteropus giganteus, held in captivity and suffering from necrosis of its wing digits, failed to respond to antibiotic therapy and succumbed to the infection. Samples submitted to the National Centre for Foreign Animal Disease were tested for viral infection. Vero E6 cells exhibited minor but unique cytopathic effects on second blind passage, and full CPE by passage four. Utilizing an unbiased random amplification technique from cell culture supernatant, we identified a bacterium belonging to the Bradyrhizobiaceae. Purification of cell culture supernatant on TY media revealed a slow growing bacterial isolate. In this study using electron microscopy, 16S rRNA gene analysis and whole genome sequencing, we identify a novel bacterial species associated with the site of infection belonging to the genus Afipia. This genus of bacteria is very diverse, with only a limited number of species characterized. Afipia felis, previously described as the etiological agent to cause cat scratch disease, and Afipia septicemium, most recently shown to cause disease in humans, highlight the potential for members of this genus to form a branch of opportunistic pathogens within the Bradyrhizobiaceae. Increased utilization of next generation sequencing and genomics will aid in classifying additional members of this intriguing bacterial genera.",2015 Apr 15,"['Pickering, Brad S.', 'Tyler, Shaun', 'Smith, Greg', 'Burton, Lynn', 'Li, Mingyi', 'Dallaire, André', 'Weingartl, Hana']",PLoS One,,,True
9a14d4a0dbda0e0ece8cca513fc9841b6cb1b2d7,PMC,Identification of a Novel Afipia Species Isolated from an Indian Flying Fox,http://dx.doi.org/10.1371/journal.pone.0121274,PMC4398416,25874801,CC BY,"An old world fruit bat Pteropus giganteus, held in captivity and suffering from necrosis of its wing digits, failed to respond to antibiotic therapy and succumbed to the infection. Samples submitted to the National Centre for Foreign Animal Disease were tested for viral infection. Vero E6 cells exhibited minor but unique cytopathic effects on second blind passage, and full CPE by passage four. Utilizing an unbiased random amplification technique from cell culture supernatant, we identified a bacterium belonging to the Bradyrhizobiaceae. Purification of cell culture supernatant on TY media revealed a slow growing bacterial isolate. In this study using electron microscopy, 16S rRNA gene analysis and whole genome sequencing, we identify a novel bacterial species associated with the site of infection belonging to the genus Afipia. This genus of bacteria is very diverse, with only a limited number of species characterized. Afipia felis, previously described as the etiological agent to cause cat scratch disease, and Afipia septicemium, most recently shown to cause disease in humans, highlight the potential for members of this genus to form a branch of opportunistic pathogens within the Bradyrhizobiaceae. Increased utilization of next generation sequencing and genomics will aid in classifying additional members of this intriguing bacterial genera.",2015 Apr 15,"['Pickering, Brad S.', 'Tyler, Shaun', 'Smith, Greg', 'Burton, Lynn', 'Li, Mingyi', 'Dallaire, André', 'Weingartl, Hana']",PLoS One,,,False
5013cc7e09951e93e65dd4b13b0af846a35cab97,PMC,Identification of a Novel Afipia Species Isolated from an Indian Flying Fox,http://dx.doi.org/10.1371/journal.pone.0121274,PMC4398416,25874801,CC BY,"An old world fruit bat Pteropus giganteus, held in captivity and suffering from necrosis of its wing digits, failed to respond to antibiotic therapy and succumbed to the infection. Samples submitted to the National Centre for Foreign Animal Disease were tested for viral infection. Vero E6 cells exhibited minor but unique cytopathic effects on second blind passage, and full CPE by passage four. Utilizing an unbiased random amplification technique from cell culture supernatant, we identified a bacterium belonging to the Bradyrhizobiaceae. Purification of cell culture supernatant on TY media revealed a slow growing bacterial isolate. In this study using electron microscopy, 16S rRNA gene analysis and whole genome sequencing, we identify a novel bacterial species associated with the site of infection belonging to the genus Afipia. This genus of bacteria is very diverse, with only a limited number of species characterized. Afipia felis, previously described as the etiological agent to cause cat scratch disease, and Afipia septicemium, most recently shown to cause disease in humans, highlight the potential for members of this genus to form a branch of opportunistic pathogens within the Bradyrhizobiaceae. Increased utilization of next generation sequencing and genomics will aid in classifying additional members of this intriguing bacterial genera.",2015 Apr 15,"['Pickering, Brad S.', 'Tyler, Shaun', 'Smith, Greg', 'Burton, Lynn', 'Li, Mingyi', 'Dallaire, André', 'Weingartl, Hana']",PLoS One,,,False
e62f6de9bc9588f663d52ae7d998bbe160485d48,PMC,Association of low serum TGF-β level in hantavirus infected patients with severe disease,http://dx.doi.org/10.1186/s12865-015-0085-0,PMC4399110,25888018,CC BY,"BACKGROUND: Hantaviruses are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome, an immune-mediated pathogenesis is discussed. The aim of the present study was to investigate the role of TGF-β expression in acute hantavirus infection. RESULTS: We retrospectively studied 77 patients hospitalised with acute Puumala infection during a hantavirus epidemic in Germany in 2012. Hantavirus infection was confirmed by positive anti-Puumala hantavirus IgG and IgM. Plasma levels of transforming growth factor (TGF)-β1 and TGF-β2 were analysed. Based on glomerular filtration rate on admission, patients were divided in mild and severe course of disease. Puumala virus RNA was detected by PCR amplification of the viral L segment gene. Out of 77 Puumala virus infected patients, 52 (68%) were male. A seasonal distribution was detected in our cohort with a peak in summer 2012, the highest incidence was observed in the age group of 30–39 years. Puumala virus RNA was detectable in 4/77 cases. Patients with severe disease had a significant longer hospital stay than patients with mild disease (6.2 vs 3.6 days). Thrombocyte count (186 vs 225 per nl), serum TGF-β1 (74 vs 118 ng/l) and TGF-β2 (479 vs 586 pg/l) were significantly lower in severe compared to mild disease. However, C-reactive protein (CRP) was significantly higher in patients with severe disease (62 vs 40 mg/l). TGF-β1/Cr was the most sensitive and specific marker associated with renal dysfunction. CONCLUSION: High serum CRP and low serum TGF-β in the early phase of hantavirus infection is associated with a severe course of disease. Our results support the hypothesis of an immune-mediated pathogenesis in hantavirus infection.",2015 Apr 14,"['Sadeghi, Mahmoud', 'Lahdou, Imad', 'Ettinger, Jakob', 'Navid, Mojdeh Heidary', 'Daniel, Volker', 'Zeier, Martin', 'Hofmann, Jörg', 'Opelz, Gerhard', 'Schnitzler, Paul']",BMC Immunol,,,True
9e7a93b167e9c3ffc970caf4a644d63439410cc5,PMC,Impact of MBL and MASP-2 gene polymorphism and its interaction on susceptibility to tuberculosis,http://dx.doi.org/10.1186/s12879-015-0879-y,PMC4399571,25887173,CC BY,"BACKGROUND: Mannose-binding lectin (MBL) and MBL-associated serine proteases 2 (MASP-2) are important proteins in the lectin pathway of the immune system. Polymorphism of MBL and MASP-2 genes may affect the serum concentration of MBL and MASP-2. This study explores the association between MBL and MASP-2 gene polymorphism and their interactions and the susceptibility to tuberculosis (TB). METHOD: A total of 503 patients with TB and 419 healthy controls were recruited to participate in this case-control study. PCR-SSP technology was applied to genotype rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes. Demographic data and some exposure information were also obtained from study participants. Unconditional logistic regression analysis was used to identify association between the various factors and TB whilst Marginal Structural Linear Odds Models were used to estimate the interactions. RESULTS: Both genotype GC at rs7096206 of MBL genes and genotype TC at rs2273346 and rs6695096 of MASP-2 genes were more prevalent in the TB patient group than the healthy control group (P < 0.05, OR 1.393, 1.302 and 1.426 respectively). The relative excess risk of interaction (RERI) between rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes was 0.897 (95% CI: 0.282, 1.513) and 1.142 (95% CI: 0.755, 1.530) respectively (P < 0.05). CONCLUSION: Polymorphisms of MBL (rs7096206) and MASP-2 (rs2273346 and rs6695096) were associated with the susceptibility of TB, and there were gene-gene interactions among them.",2015 Mar 25,"['Chen, Mengshi', 'Liang, Ying', 'Li, Wufei', 'Wang, Mian', 'Hu, Li', 'Abuaku, Benjamin Kwaku', 'Huang, Xin', 'Tan, Hongzhuan', 'Wen, Shi Wu']",BMC Infect Dis,,,True
035f1d6b6c461d045fd19d69e4e9c1de221f4a0d,PMC,Synthetic lethals in HIV: ways to avoid drug resistance: Running title: Preventing HIV resistance,http://dx.doi.org/10.1186/s13062-015-0044-y,PMC4399722,25888435,CC BY,"BACKGROUND: RNA viruses rapidly accumulate genetic variation, which can give rise to synthetic lethal (SL) and deleterious (SD) mutations. Synthetic lethal mutations (non-lethal when alone but lethal when combined in one genome) have been studied to develop cancer therapies. This principle can also be used against fast-evolving RNA-viruses. Indeed, targeting protein sites involved in SD + SL interactions with a drug would render any mutation of such sites, lethal. RESULTS: Here, we set up a strategy to detect intragenic pairs of SL and SD at the surface of the protein to predict less escapable drug target sites. For this, we detected SD + SL, studying HIV protease (PR) and reverse transcriptase (RT) sequence alignments from two groups of VIH(+) individuals: treated with drugs (T) or not (NT). Using a series of statistical approaches, we were able to propose bona fide SD + SL couples. When focusing on spatially close co-variant SD + SL couples at the surface of the protein, we found 5 SD + SL groups (2 in the protease and 3 in the reverse transcriptase), which could be good candidates to form pockets to accommodate potential drugs. CONCLUSIONS: Thus, designing drugs targeting these specific SD + SL groups would not allow the virus to mutate any residue involved in such groups without losing an essential function. Moreover, we also show that the selection pressure induced by the treatment leads to the appearance of new mutations, which change the mutational landscape of the protein. This drives the existence of differential SD + SL couples between the drug-treated and non-treated groups. Thus, new anti-viral drugs should be designed differently to target such groups. REVIEWERS: This article was reviewed by Neil Greenspan Csaba Pal and István Simon. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13062-015-0044-y) contains supplementary material, which is available to authorized users.",2015 Apr 17,"['Petitjean, Michel', 'Badel, Anne', 'Veitia, Reiner A', 'Vanet, Anne']",Biol Direct,,,True
774e74e60cb62c3057145f6b98501fe532acdbdd,PMC,Development and Application of an ELISA for the Detection of Porcine Deltacoronavirus IgG Antibodies,http://dx.doi.org/10.1371/journal.pone.0124363,PMC4399883,25881086,CC BY,"Porcine deltacoronavirus (PDCoV), also known as porcine coronavirus HKU15, was first detected in North America in early 2014 and associated with enteric disease in pigs, resulting in an urgent need to further investigate the ecology of this virus. While assays detecting nucleic acids were implemented quickly, assays to detect anti-PDCoV antibodies have not been available. In this study, an indirect anti-PDCoV IgG enzyme-linked immunosorbent assay (ELISA) based on the putative S1 portion of the spike protein was developed and utilized to determine the prevalence of anti-PDCoV IgG in U.S. pigs. The diagnostic sensitivity of the PDCoV ELISA was 91% with a diagnostic specificity of 95%. A total of 968 serum samples were tested including samples with confirmed infection with PDCoV, porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus or porcine respiratory coronavirus. There was no cross-reactivity with any of the other coronaviruses. Among 355 arbitrarily selected serum samples collected in 2014 and originating from 51 farms across 18 U.S. states, anti-PDCoV IgG antibodies were detected in 8.7% of the samples and in 25.5% of the farms whereas anti-PEDV IgG was detected in 22.8% of the samples and in 54.9% of the farms. In addition, anti-PDCoV IgG antibodies were detected in archived samples collected in 2010, perhaps indicating an earlier undetected introduction into the U.S. pig population. Overall, the obtained data suggest that PDCoV seroprevalence in U.S. pigs is lower compared to PEDV and PDCoV may have been introduced to the U.S. prior to PEDV.",2015 Apr 16,"['Thachil, Anil', 'Gerber, Priscilla F.', 'Xiao, Chao-Ting', 'Huang, Yao-Wei', 'Opriessnig, Tanja']",PLoS One,,,True
220fbe1f5e79e25737c0624de9a4245bfee48ec0,PMC,Complete genome sequence of canine astrovirus with molecular and epidemiological characterisation of UK strains,http://dx.doi.org/10.1016/j.vetmic.2015.03.011,PMC4401448,25818578,CC BY,"Astroviruses are a common cause of gastroenteritis in children worldwide. These viruses can also cause infection in a range of domestic and wild animal species. Canine astrovirus (CaAstV) was first identified in the USA, and has since been reported in dogs from Europe, the Far East and South America. We sought to determine whether CaAstV is circulating in the UK dog population, and to characterise any identified strains. Stool samples were collected from pet dogs in the UK with and without gastroenteritis, and samples were screened for CaAstV by qPCR. Four CaAstV positive samples were identified from dogs with gastroenteritis (4/67, 6.0%), whereas no samples from healthy dogs were positive (p < 0.001). Sequencing of the capsid sequences from the four CaAstV strains found significant genetic heterogeneity, with only 80% amino acid identity between strains. The full genome sequence of two UK CaAstV strains was then determined, confirming that CaAstV conforms to the classic genome organisation of other astroviruses with ORF1a and ORF1b separated by a frameshift and ORF2 encoding the capsid protein. This is the first report describing the circulation of CaAstV in UK dogs with clinical signs of gastroenteritis, and the first description of the full-length genomes of two CaAstV strains.",2015 May 15,"['Caddy, Sarah L.', 'Goodfellow, Ian']",Vet Microbiol,,,False
95ab4b0ddc015a430ed865c9cdd105f1e50faf31,PMC,Phase 1 Study of Pandemic H1 DNA Vaccine in Healthy Adults,http://dx.doi.org/10.1371/journal.pone.0123969,PMC4401709,25884189,CC0,"BACKGROUND: A novel, swine-origin influenza A (H1N1) virus was detected worldwide in April 2009, and the World Health Organization (WHO) declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1) influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1) licensed monovalent inactivated vaccine (MIV). METHODS: 20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector) at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3–17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry. RESULTS: Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine. CONCLUSIONS: H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics. TRIAL REGISTRATION: Clinicaltrials.gov NCT00973895",2015 Apr 17,"['Crank, Michelle C.', 'Gordon, Ingelise J.', 'Yamshchikov, Galina V.', 'Sitar, Sandra', 'Hu, Zonghui', 'Enama, Mary E.', 'Holman, LaSonji A.', 'Bailer, Robert T.', 'Pearce, Melissa B.', 'Koup, Richard A.', 'Mascola, John R.', 'Nabel, Gary J.', 'Tumpey, Terrence M.', 'Schwartz, Richard M.', 'Graham, Barney S.', 'Ledgerwood, Julie E.', None]",PLoS One,,,True
27ada359a2b9536a180bd93585f47a13d5b82517,PMC,Phase 1 Study of Pandemic H1 DNA Vaccine in Healthy Adults,http://dx.doi.org/10.1371/journal.pone.0123969,PMC4401709,25884189,CC0,"BACKGROUND: A novel, swine-origin influenza A (H1N1) virus was detected worldwide in April 2009, and the World Health Organization (WHO) declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1) influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1) licensed monovalent inactivated vaccine (MIV). METHODS: 20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector) at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3–17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry. RESULTS: Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine. CONCLUSIONS: H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics. TRIAL REGISTRATION: Clinicaltrials.gov NCT00973895",2015 Apr 17,"['Crank, Michelle C.', 'Gordon, Ingelise J.', 'Yamshchikov, Galina V.', 'Sitar, Sandra', 'Hu, Zonghui', 'Enama, Mary E.', 'Holman, LaSonji A.', 'Bailer, Robert T.', 'Pearce, Melissa B.', 'Koup, Richard A.', 'Mascola, John R.', 'Nabel, Gary J.', 'Tumpey, Terrence M.', 'Schwartz, Richard M.', 'Graham, Barney S.', 'Ledgerwood, Julie E.', None]",PLoS One,,,True
0ca8648d40bee3056b3f9840de6d34b57ed121d0,PMC,Infectious Bursal Disease Virus VP5 Polypeptide: A Phosphoinositide-Binding Protein Required for Efficient Cell-to-Cell Virus Dissemination,http://dx.doi.org/10.1371/journal.pone.0123470,PMC4401730,25886023,CC BY,"Infectious bursal disease virus (IBDV), a member of the Birnaviridae family, is a major avian pathogen responsible for an immunosuppressive disease affecting juvenile chickens. The IBDV genome is formed by two dsRNA segments. The largest one harbors two partially overlapping open reading frames encoding a non-structural polypeptide, known as VP5, and a large polyprotein, respectively. VP5 is non-essential for virus replication. However, it plays a major role in IBDV pathogenesis. VP5 accumulates at the plasma membrane (PM) of IBDV-infected cells. We have analyzed the mechanism underlying the VP5 PM targeting. Updated topological prediction algorithm servers fail to identify a transmembrane domain within the VP5 sequence. However, the VP5 polycationic C-terminal region, harboring three closely spaced patches formed by two or three consecutive basic amino acid residues (lysine or arginine), might account for its PM tropism. We have found that mutations, either C-terminal VP5 deletions or replacement of basic amino acids by alanine residues, that reduce the electropositive charge of the VP5 C-terminus abolish PM targeting. Lipid overlay assays performed with an affinity-purified Flag-tagged VP5 (FVP5) protein version show that this polypeptide binds several phosphoinositides (PIP), exhibiting a clear preference for monophosphate species. Experiments performed with FVP5 mutant proteins lacking the polycationic domain demonstrate that this region is essential for PIP binding. Data gathered with IBDV mutants expressing C-terminal deleted VP5 polypeptides generated by reverse genetics demonstrate that the VP5-PIP binding domain is required both for its PM targeting in infected cells, and for efficient virus dissemination. Data presented here lead us to hypothesize that IBDV might use a non-lytic VP5-dependent cell-to-cell spreading mechanism.",2015 Apr 17,"['Méndez, Fernando', 'de Garay, Tomás', 'Rodríguez, Dolores', 'Rodríguez, José F.']",PLoS One,,,True
8f11a3876dfbf3ba4a143b9e2ad122b8c2b9c2be,PMC,An ensemble strategy that significantly improves de novo assembly of microbial genomes from metagenomic next-generation sequencing data,http://dx.doi.org/10.1093/nar/gkv002,PMC4402509,25586223,CC BY,"Next-generation sequencing (NGS) approaches rapidly produce millions to billions of short reads, which allow pathogen detection and discovery in human clinical, animal and environmental samples. A major limitation of sequence homology-based identification for highly divergent microorganisms is the short length of reads generated by most highly parallel sequencing technologies. Short reads require a high level of sequence similarities to annotated genes to confidently predict gene function or homology. Such recognition of highly divergent homologues can be improved by reference-free (de novo) assembly of short overlapping sequence reads into larger contigs. We describe an ensemble strategy that integrates the sequential use of various de Bruijn graph and overlap-layout-consensus assemblers with a novel partitioned sub-assembly approach. We also proposed new quality metrics that are suitable for evaluating metagenome de novo assembly. We demonstrate that this new ensemble strategy tested using in silico spike-in, clinical and environmental NGS datasets achieved significantly better contigs than current approaches.",2015 Apr 20,"['Deng, Xutao', 'Naccache, Samia N.', 'Ng, Terry', 'Federman, Scot', 'Li, Linlin', 'Chiu, Charles Y.', 'Delwart, Eric L.']",Nucleic Acids Res,,,True
9d6c0c6b233bdffc9a3a85e7fe255163b54ca658,PMC,mRNA maturation in giant viruses: variation on a theme,http://dx.doi.org/10.1093/nar/gkv224,PMC4402537,25779049,CC BY,"Giant viruses from the Mimiviridae family replicate entirely in their host cytoplasm where their genes are transcribed by a viral transcription apparatus. mRNA polyadenylation uniquely occurs at hairpin-forming palindromic sequences terminating viral transcripts. Here we show that a conserved gene cluster both encode the enzyme responsible for the hairpin cleavage and the viral polyA polymerases (vPAP). Unexpectedly, the vPAPs are homodimeric and uniquely self-processive. The vPAP backbone structures exhibit a symmetrical architecture with two subdomains sharing a nucleotidyltransferase topology, suggesting that vPAPs originate from an ancestral duplication. A Poxvirus processivity factor homologue encoded by Megavirus chilensis displays a conserved 5′-GpppA 2′O methyltransferase activity but is also able to internally methylate the mRNAs’ polyA tails. These findings elucidate how the arm wrestling between hosts and their viruses to access the translation machinery is taking place in Mimiviridae.",2015 Apr 20,"['Priet, Stéphane', 'Lartigue, Audrey', 'Debart, Françoise', 'Claverie, Jean-Michel', 'Abergel, Chantal']",Nucleic Acids Res,,,True
e4bc8603739ef592b4ce5c2a3b92abd82a2a13ef,PMC,Preparation and Antibacterial Activity Evaluation of 18-β-glycyrrhetinic Acid Loaded PLGA Nanoparticles,,PMC4403053,25901144,CC BY,"The aim of the present study was to formulate poly (lactide-co-glycolide) (PLGA) nanoparticles loaded with 18-β-glycyrrhetinic acid (GLA) with appropriate physicochemical properties and antimicrobial activity. GLA loaded PLGA nanoparticles were prepared with different drug to polymer ratios, acetone contents and sonication times and the antibacterial activity of the developed nanoparticles was examined against different gram-negative and gram-positive bacteria. The antibacterial effect was studied using serial dilution technique to determine the minimum inhibitory concentration of nanoparticles. Results demonstrated that physicochemical properties of nanoparticles were affected by the above mentioned parameters where nanoscale size particles ranging from 175 to 212 nm were achieved. The highest encapsulation efficiency (53.2 ± 2.4%) was obtained when the ratio of drug to polymer was 1:4. Zeta potential of the developed nanoparticles was fairly negative (-11±1.5). In-vitro release profile of nanoparticles showed two phases: an initial phase of burst release for 10 h followed by a slow release pattern up to the end. The antimicrobial results revealed that the nanoparticles were more effective than pure GLA against P. aeuroginosa, S. aureus and S. epidermidis. This improvement in antibacterial activity of GLA loaded nanoparticles when compared to pure GLA may be related to higher nanoparticles penetration into infected cells and a higher amount of GLA delivery in its site of action. Herein, it was shown that GLA loaded PLGA nanoparticles displayed appropriate physicochemical properties as well as an improved antimicrobial effect.",2015 Spring,"['Darvishi, Behrad', 'Manoochehri, Saeed', 'Kamalinia, Golnaz', 'Samadi, Nasrin', 'Amini, Mohsen', 'Mostafavi, Seyyed Hossein', 'Maghazei, Shahab', 'Atyabi, Fatemeh', 'Dinarvand, Rassoul']",Iran J Pharm Res,,,True
c047b0340f79e0d34787e5f3500605b8c20e827d,PMC,Local Evolutionary Patterns of Human Respiratory Syncytial Virus Derived from Whole-Genome Sequencing,http://dx.doi.org/10.1128/JVI.03391-14,PMC4403408,25609811,CC BY,"Human respiratory syncytial virus (RSV) is associated with severe childhood respiratory infections. A clear description of local RSV molecular epidemiology, evolution, and transmission requires detailed sequence data and can inform new strategies for virus control and vaccine development. We have generated 27 complete or nearly complete genomes of RSV from hospitalized children attending a rural coastal district hospital in Kilifi, Kenya, over a 10-year period using a novel full-genome deep-sequencing process. Phylogenetic analysis of the new genomes demonstrated the existence and cocirculation of multiple genotypes in both RSV A and B groups in Kilifi. Comparison of local versus global strains demonstrated that most RSV A variants observed locally in Kilifi were also seen in other parts of the world, while the Kilifi RSV B genomes encoded a high degree of variation that was not observed in other parts of the world. The nucleotide substitution rates for the individual open reading frames (ORFs) were highest in the regions encoding the attachment (G) glycoprotein and the NS2 protein. The analysis of RSV full genomes, compared to subgenomic regions, provided more precise estimates of the RSV sequence changes and revealed important patterns of RSV genomic variation and global movement. The novel sequencing method and the new RSV genomic sequences reported here expand our knowledge base for large-scale RSV epidemiological and transmission studies. IMPORTANCE The new RSV genomic sequences and the novel sequencing method reported here provide important data for understanding RSV transmission and vaccine development. Given the complex interplay between RSV A and RSV B infections, the existence of local RSV B evolution is an important factor in vaccine deployment.",2015 Jan 21,"['Agoti, Charles N.', 'Otieno, James R.', 'Munywoki, Patrick K.', 'Mwihuri, Alexander G.', 'Cane, Patricia A.', 'Nokes, D. James', 'Kellam, Paul', 'Cotten, Matthew']",J Virol,,,True
50ff548ec63f21fdb34fbdfe8fab41141c65fcb5,PMC,Herpes Simplex Virus-1 Fine-Tunes Host’s Autophagic Response to Infection: A Comprehensive Analysis in Productive Infection Models,http://dx.doi.org/10.1371/journal.pone.0124646,PMC4403807,25894397,CC BY,"Herpes simplex virus-1 (HSV-1) infection causes severe conditions, with serious complications, including corneal blindness from uncontrolled ocular infections. An important cellular defense mechanism against HSV-1 infection is autophagy. The autophagic response of the host cell was suggested to be regulated by HSV-1. In this study, we performed a detailed analysis of autophagy in multiple HSV-1-targeted cell types, and under various infection conditions that recapitulate a productive infection model. We found that autophagy was slightly inhibited in one cell type, while in other cell types autophagy maintained its basal levels mostly unchanged during productive infection. This study refines the concept of HSV-1-mediated autophagy regulation to imply either inhibition, or prevention of activation, of the innate immune pathway.",2015 Apr 20,"['Yakoub, Abraam M.', 'Shukla, Deepak']",PLoS One,,,True
395fef2b73d1c568f900de94f5f6d908bc305f24,PMC,Detection of new genetic variants of Betacoronaviruses in Endemic Frugivorous Bats of Madagascar,http://dx.doi.org/10.1186/s12985-015-0271-y,PMC4404003,25888853,CC BY,"BACKGROUND: Bats are amongst the natural reservoirs of many coronaviruses (CoVs) of which some can lead to severe infection in human. African bats are known to harbor a range of pathogens (e.g., Ebola and Marburg viruses) that can infect humans and cause disease outbreaks. A recent study in South Africa isolated a genetic variant closely related to MERS-CoV from an insectivorous bat. Though Madagascar is home to 44 bat species (41 insectivorous and 3 frugivorous) of which 34 are endemic, no data exists concerning the circulation of CoVs in the island’s chiropteran fauna. Certain Malagasy bats can be frequently found in close contact with humans and frugivorous bats feed in the same trees where people collect and consume fruits and are hunted and consumed as bush meat. The purpose of our study is to detect and identify CoVs from frugivorous bats in Madagascar to evaluate the risk of human infection from infected bats. METHODS: Frugivorous bats belonging to three species were captured in four different regions of Madagascar. We analyzed fecal and throat swabs to detect the presence of virus through amplification of the RNA-dependent RNA polymerase (RdRp) gene, which is highly conserved in all known coronaviruses. Phylogenetic analyses were performed from positive specimens. RESULTS: From 351 frugivorous bats, we detected 14 coronaviruses from two endemic bats species, of which 13 viruses were identified from Pteropus rufus and one from Eidolon dupreanum, giving an overall prevalence of 4.5%. Phylogenetic analysis revealed that the Malagasy strains belong to the genus Betacoronavirus but form three distinct clusters, which seem to represent previously undescribed genetic lineages. CONCLUSIONS: Our findings suggest that CoVs circulate in frugivorous bats of Madagascar, demonstrating the needs to evaluate spillover risk to human populations especially for individuals that hunt and consume infected bats. Possible dispersal mechanisms as to how coronaviruses arrived on Madagascar are discussed.",2015 Mar 12,"['Razanajatovo, Norosoa H', 'Nomenjanahary, Lalaina A', 'Wilkinson, David A', 'Razafimanahaka, Julie H', 'Goodman, Steven M', 'Jenkins, Richard K', 'Jones, Julia PG', 'Heraud, Jean-Michel']",Virol J,,,True
72e1f47796b2283c03f3d7aa4f6044592f8c198d,PMC,An inactivated vaccine made from a U.S. field isolate of porcine epidemic disease virus is immunogenic in pigs as demonstrated by a dose-titration,http://dx.doi.org/10.1186/s12917-015-0357-1,PMC4404228,25881296,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV), a highly pathogenic and transmissible virus in swine, was first detected in the U.S. in May, 2013, and has caused tremendous losses to the swine industry. Due to the difficulty in isolating and growing this virus in cell culture, few vaccine studies using cell culture propagated PEDV have been performed on U.S. strains in pigs. Therefore, the objective of this study was to evaluate the humoral immune response to the selected inactivated PEDV vaccine candidate in a dose-titration manner. RESULTS: PEDV was isolated from a pig with diarrhea and complete genome sequencing found >99% nucleotide identity to other U.S. PEDV. Inactivated adjuvanted monovalent vaccines were administered intramuscularly to five week old pigs in a dose titration experimental design, ranging from 6.0-8.0 log(10) tissue culture infective dose (TCID(50)/mL), to evaluate immunogenicity using a fluorescent foci neutralization assay (FFN), fluorescent microsphere immunoassay (FMIA), and enzyme-linked immunosorbent assay (ELISA) on sera. Pigs vaccinated with 8.0 log(10) TCID(50)/mL inactivated virus showed significantly higher FFN titers as well as FMIA and ELISA values than 6.0 log(10) TCID(50)/mL vaccinates and the negative controls. CONCLUSIONS: These results demonstrate the immunogenicity of a PEDV inactivated viral vaccine with a U.S. strain via dose-titration. A future vaccination-challenge study would illustrate the efficacy of an inactivated vaccine and help evaluate protective FFN titers and ELISA and FMIA responses.",2015 Mar 15,"['Collin, Emily A', 'Anbalagan, Srivishnupriya', 'Okda, Faten', 'Batman, Ron', 'Nelson, Eric', 'Hause, Ben M']",BMC Vet Res,,,True
79ffac5ab7acd3c43a3e0866ed150fea9a0ec1c8,PMC,"BAP31, a promising target for the immunotherapy of malignant melanomas",http://dx.doi.org/10.1186/s13046-015-0153-6,PMC4405826,25903101,CC BY,"PURPOSE: Malignant melanoma’s (MM) incidence is rising faster than that of any other cancer in the US and the overall survival at 5 years is less than 10%. B cell associated protein 31 (BAP31) is overexpressed in most MMs and might be a promising target for immunotherapy of this disease. EXPERIMENTAL DESIGN: Firstly, we investigated the expression profiles of human BAP31 (hBAP31) and mouse BAP31 (mBAP31) in human and mouse normal tissues, respectively. The expression level of hBAP31 in human MMs and mBAP31 in B16 melanoma cells was also analyzed. Then we constructed novel mBAP31 DNA vaccines and tested there ability to stimulate mBAP31-specific immune responses and antitumor immunity in B16 melanoma-bearing mice. RESULTS: For the first time, we found that protein expression of hBAP31 were dramatically upregulated in human MMs when compared with human normal tissues. Predominant protein expression of mBAP31 was found in mouse B16 melanoma cells but not in mouse important organs. When mice were immunized with mBAP31 DNA vaccines, strong cellular response to mBAP31 was observed in the vaccinated mice. CTLs isolated from immunized mice could effectively kill mBAP31-positive target mouse B16 melanoma tumor cells in vitro and vaccination with mBAP31 DNA vaccines had potent anti-tumor activity in therapeutic model using B16 melanoma cells. CONCLUSIONS: These are the first data supporting a vaccine targeting BAP31 that is capable of inducing effective immunity against BAP31-expressing MMs and will be applicable to human MMs and hBAP31 DNA vaccine warrants investigation in human clinical trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-015-0153-6) contains supplementary material, which is available to authorized users.",2015 Apr 18,"['Yu, Shaojuan', 'Wang, Fuli', 'Fan, Li', 'Wei, Yuying', 'Li, Haitao', 'Sun, Yuanjie', 'Yang, Angang', 'Jin, Boquan', 'Song, Chaojun', 'Yang, Kun']",J Exp Clin Cancer Res,,,True
88e8809f280ef47d36f3e56b7f8558c303f36742,PMC,An educational programme for nursing college staff and students during a MERS- coronavirus outbreak in Saudi Arabia,http://dx.doi.org/10.1186/s12912-015-0065-y,PMC4405869,25904821,CC BY,"BACKGROUND: The Middle Eastern Respiratory Syndrome Coronavirus is a serious and emerging issue in Saudi Arabia and the world. A response was required to reduce possible disease transmission between the hospital and university. College of Nursing academic staff developed a programme in response to the educational and emotional needs of participants. METHODS: A MERS-CoV Task Force responded to the rapidly unfolding epidemic. The aim was to find out what nursing staff and nursing students in the college knew about MERS- CoV. While most gaps in knowledge were addressed after an intense information seminar, other learning needs were identified and responded to. The Task Force developed mandatory information sessions for all nursing faculty, students and staff. All staff were informed by email, letters and posters. There are 28 faculty staff, 84 support staff and 480 students in the College of Nursing. The information settings all took place within the College of Nursing, Princess Nourah University, Kingdom of Saudi Arabia. Questionnaires were given to faculty, students and staff to understand their baseline knowledge. After the sessions, faculty, students and staff were asked about what was learned through the sessions, and what educational needs still needed to be addressed. Approval was sought and received by the Ethics Committee for the College of Nursing. Participants completed informed consent forms and the voluntary nature of the study was explained. RESULTS: The total number of people attending the education sessions was133, including 65 students. 18 faculty members attended and 57 support staff. Data was gathered on gaps in participant knowledge and a plan was developed to address the gaps. Policies were established around student participation in clinical and return to work practices for staff with any symptoms. CONCLUSION: In hospitals there is above average risk for exposure to infectious diseases. Student nurses travel between hospital and university, with the capacity to act as a conduit of pathogens to large, susceptible populations. Nursing colleges must respond thoroughly to protect students and staff and prevent spread of disease into the university community in the midst of an epidemic.",2015 Apr 16,"['Stirling, Bridget V', 'Harmston, Jennie', 'Alsobayel, Hana']",BMC Nurs,,,True
424cd6cb670119aed604833cf1f107598f217574,PMC,Astragalin inhibits autophagy-associated airway epithelial fibrosis,http://dx.doi.org/10.1186/s12931-015-0211-9,PMC4406173,25895672,CC BY,"BACKGROUND: Fibrotic remodeling of airway and lung parenchymal compartments is attributed to pulmonary dysfunction with an involvement of reactive oxygen species (ROS) in chronic lung diseases such as idiopathic pulmonary fibrosis and asthma. METHODS: The in vitro study elucidated inhibitory effects of astragalin, kaempferol-3-O-glucoside from leaves of persimmon and green tea seeds, on oxidative stress-induced airway fibrosis. The in vivo study explored the demoting effects of astragalin on epithelial to mesenchymal transition in BALB/c mice sensitized with ovalbumin (OVA). RESULTS: The exposure of 20 μM H(2)O(2) for 72 h accelerated E-cadherin loss and vimentin induction in airway epithelial BEAS-2B cells, which was reversed by non-toxic astragalin at 1–20 μM. Astragalin allayed the airway tissue levels of ROS and vimentin enhanced by OVA challenge. Collagen type 1 production increased in H(2)O(2)–exposed epithelial cells and collagen fiber deposition was observed in OVA-challenged mouse airways. This study further investigated that the oxidative stress-triggered autophagic regulation was responsible for inducing airway fibrosis. H(2)O(2) highly enhanced the expression induction of the autophagy-related beclin-1 and light chains 3A/B (LC3A/B) within 4 h and astragalin blocked such induction by H(2)O(2). This compound deterred the ROS-promoted autophagosome formation in BEAS-2B cells. Consistently, in OVA-sensitized mice the expression of beclin-1 and LC3A/B was highly induced, and oral administration of astragalin suppressed the autophagosome formation with inhibiting the induction of these proteins in OVA-challenged airway subepithelium. Induction of autophagy by spermidine influenced the epithelial induction of E-cadherin and vimentin that was blocked by treating astragalin. CONCLUSION: These results demonstrate that astragalin can be effective in allaying ROS-promoted bronchial fibrosis through inhibiting autophagosome formation in airways.",2015 Apr 21,"['Cho, In-Hee', 'Choi, Yean-Jung', 'Gong, Ju-Hyun', 'Shin, Daekeun', 'Kang, Min-Kyung', 'Kang, Young-Hee']",Respir Res,,,True
e35886a4c45a6f26a17e68185b4172fb32ceb452,PMC,Isolation of Single-Stranded DNA Aptamers That Distinguish Influenza Virus Hemagglutinin Subtype H1 from H5,http://dx.doi.org/10.1371/journal.pone.0125060,PMC4406500,25901739,CC BY,"Surface protein hemagglutinin (HA) mediates the binding of influenza virus to host cell receptors containing sialic acid, facilitating the entry of the virus into host cells. Therefore, the HA protein is regarded as a suitable target for the development of influenza virus detection devices. In this study, we isolated single-stranded DNA (ssDNA) aptamers binding to the HA1 subunit of subtype H1 (H1-HA1), but not to the HA1 subunit of subtype H5 (H5-HA1), using a counter-systematic evolution of ligands by exponential enrichment (counter-SELEX) procedure. Enzyme-linked immunosorbent assay and surface plasmon resonance studies showed that the selected aptamers bind tightly to H1-HA1 with dissociation constants in the nanomolar range. Western blot analysis demonstrated that the aptamers were binding to H1-HA1 in a concentration-dependent manner, yet were not binding to H5-HA1. Interestingly, the selected aptamers contained G-rich sequences in the central random nucleotides region. Further biophysical analysis showed that the G-rich sequences formed a G-quadruplex structure, which is a distinctive structure compared to the starting ssDNA library. Using flow cytometry analysis, we found that the aptamers did not bind to the receptor-binding site of H1-HA1. These results indicate that the selected aptamers that distinguish H1-HA1 from H5-HA1 can be developed as unique probes for the detection of the H1 subtype of influenza virus.",2015 Apr 22,"['Woo, Hye-Min', 'Lee, Jin-Moo', 'Yim, Sanggyu', 'Jeong, Yong-Joo']",PLoS One,,,True
c1edf39ded74b76134cc304dd347a4eb20bae012,PMC,The Importance of Bacterial and Viral Infections Associated with Adult Asthma Exacerbations in Clinical Practice,http://dx.doi.org/10.1371/journal.pone.0123584,PMC4406689,25901797,CC BY,"BACKGROUND: Viral infection is one of the risk factors for asthma exacerbation. However, which pathogens are related to asthma exacerbation in adults remains unclear. OBJECTIVE: The relation between various infections and adult asthma exacerbations was investigated in clinical practice. METHODS: The study subjects included 50 adult inpatients due to asthma exacerbations and 20 stable outpatients for comparison. The pathogens from a nasopharyngeal swab were measured by multiplex PCR analysis. RESULTS: Asthma exacerbations occurred after a common cold in 48 inpatients. The numbers of patients with viral, bacterial, or both infections were 16, 9, and 9, respectively. The dominant viruses were rhinoviruses, respiratory syncytial virus, influenza virus, and metapneumovirus. The major bacteria were S. pneumoniae and H. influenzae. Compared to pathogen-free patients, the patients with pathogens were older and non-atopic and had later onset of disease, lower FeNO levels, lower IgE titers, and a higher incidence of comorbid sinusitis, COPD, or pneumonia. Compared to stable outpatients, asthma exacerbation inpatients had a higher incidence of smoking and comorbid sinusitis, COPD, or pneumonia. Viruses were detected in 50% of stable outpatients, but a higher incidence of rhinovirus, respiratory syncytial virus, and metapneumovirus infections was observed in asthma exacerbation inpatients. H. influenzae was observed in stable asthmatic patients. Other bacteria, especially S. pneumoniae, were important in asthma exacerbation inpatients. CONCLUSION: Viral or bacterial infections were observed in 70% of inpatients with an asthma exacerbation in clinical practice. Infection with S. pneumoniae was related to adult asthma exacerbation.",2015 Apr 22,"['Iikura, Motoyasu', 'Hojo, Masayuki', 'Koketsu, Rikiya', 'Watanabe, Sho', 'Sato, Ayano', 'Chino, Haruka', 'Ro, Shoki', 'Masaki, Haruna', 'Hirashima, Junko', 'Ishii, Satoru', 'Naka, Go', 'Takasaki, Jin', 'Izumi, Shinyu', 'Kobayashi, Nobuyuki', 'Yamaguchi, Sachiko', 'Nakae, Susumu', 'Sugiyama, Haruhito']",PLoS One,,,True
73f93646de4efa4c3b8d02d07dea684c028763d1,PMC,Investigation of Pathogenesis of H1N1 Influenza Virus and Swine Streptococcus suis Serotype 2 Co-Infection in Pigs by Microarray Analysis,http://dx.doi.org/10.1371/journal.pone.0124086,PMC4407888,25906258,CC BY,"Swine influenza virus and Streptococcus suis are two important contributors to the porcine respiratory disease complex, and both have significant economic impacts. Clinically, influenza virus and Streptococcus suis co-infections in pigs are very common, which often contribute to severe pneumonia and can increase the mortality. However, the co-infection pathogenesis in pigs is unclear. In the present study, co-infection experiments were performed using swine H1N1 influenza virus and Streptococcus suis serotype 2 (SS2). The H1N1-SS2 co-infected pigs exhibited more severe clinical symptoms, serious pathological changes, and robust apoptosis of lungs at 6 days post-infection compared with separate H1N1 and SS2 infections. A comprehensive gene expression profiling using a microarray approach was performed to investigate the global host responses of swine lungs against the swine H1N1 infection, SS2 infection, co-infection, and phosphate-buffered saline control. Results showed 457, 411, and 844 differentially expressed genes in the H1N1, SS2, and H1N1-SS2 groups, respectively, compared with the control. Noticeably, genes associated with the immune, inflammatory, and apoptosis responses were highly overexpressed in the co-infected group. Pathway analysis indicated that the cytokine–cytokine receptor interactions, MAPK, toll-like receptor, complement and coagulation cascades, antigen processing and presentation, and apoptosis pathway were significantly regulated in the co-infected group. However, the genes related to these were less regulated in the separate H1N1 and SS2 infection groups. This observation suggested that a certain level of synergy was induced by H1N1 and SS2 co-infection with significantly stronger inflammatory and apoptosis responses, which may lead to more serious respiratory disease syndrome and pulmonary pathological lesion.",2015 Apr 23,"['Lin, Xian', 'Huang, Canhui', 'Shi, Jian', 'Wang, Ruifang', 'Sun, Xin', 'Liu, Xiaokun', 'Zhao, Lianzhong', 'Jin, Meilin']",PLoS One,,,True
f74ee87b0db54450d2684da633a56b6f159a6c0b,PMC,The Ebola Epidemic Crystallizes the Potential of Passive Antibody Therapy for Infectious Diseases,http://dx.doi.org/10.1371/journal.ppat.1004717,PMC4408073,25905897,CC BY,,2015 Apr 23,"['Casadevall, Arturo', 'Pirofski, Liise-anne']",PLoS Pathog,,,True
7b1a62bfe713b9fe81bb84360d31590a6083b499,PMC,A Functional Role of Fibroblast Growth Factor Receptor 1 (FGFR1) in the Suppression of Influenza A Virus Replication,http://dx.doi.org/10.1371/journal.pone.0124651,PMC4409105,25909503,CC BY,"Influenza A virus causes annual epidemics and occasional pandemics in humans. Here, we investigated four members of the fibroblast growth factor receptor (FGFR) family; FGFR1 to 4, and examined their expression patterns in human lung epithelial cells A549 with influenza A virus infection. We identified a functional role of FGFR1 in influenza A/Puerto Rico/8/1934 (PR8) and A/Anhui/01/2005 (H5N1) virus replication. Our results showed that FGFR1 silencing by siRNA interference promoted influenza A/PR8 and H5N1 virus replication in A549 cells, while lentivirus-mediated exogenous FGFR1 expression significantly suppressed influenza A virus replication; however, FGFR4 did not have the same effects. Moreover, FGFR1 phosphorylation levels were downregulated in A549 cells by influenza A virus infection, while the repression of FGFR1 kinase using PD173074, a potent and selective FGFR1 inhibitor, could enhance virus replication. Furthermore, we found that FGFR1 inhibits influenza virus internalization, but not binding, during viral entry. These results suggested that FGFR1 specifically antagonizes influenza A virus replication, probably by blocking viral entry.",2015 Apr 24,"['Liu, Xin', 'Lai, Chengcai', 'Wang, Keyu', 'Xing, Li', 'Yang, Penghui', 'Duan, Qing', 'Wang, Xiliang']",PLoS One,,,True
88ccb20962dc958fc239c0ef5bed963cfd782b65,PMC,The Ebola epidemic is ongoing in West Africa and responses from China are positive,http://dx.doi.org/10.1186/s40779-015-0031-8,PMC4409763,25914830,CC BY,"The ongoing Ebola outbreak poses an alarming risk to the countries of West Africa and beyond. On August 8, 2014, the World Health Organization (WHO) declared the cross-country Ebola outbreak a Public Emergency of International Concern. China has had no confirmed cases of Ebola. In this paper, virologic characteristics, pathogenesis, clinical manifestations, laboratory examination and prophylactic vaccines and therapeutic drugs of Ebola are summarized. Importantly, active responses and actions from China are introduced. Moreover, the key issues in the future prevention and control of Ebola were also addressed.",2015 Apr 3,"['Zhao, Jing-Min', 'Dong, Shi-Jun', 'Li, Jin', 'Ji, Jun-Sheng']",Mil Med Res,,,True
c8233094deb36e03c7c73fd03f3bab601498e563,PMC,A comprehensive collection of systems biology data characterizing the host response to viral infection,http://dx.doi.org/10.1038/sdata.2014.33,PMC4410982,25977790,CC BY,"The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated. Study validation was demonstrated via experimental quality control measures and meta-analysis of independent experiments performed under similar conditions. Primary assay results are archived at the GEO and PeptideAtlas public repositories, while processed statistical results together with standardized metadata are publically available at the Influenza Research Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). By comparing data from mutant versus wild-type virus and host strains, RNA versus protein differential expression, and infection with genetically similar strains, these data can be used to further investigate genetic and physiological determinants of host responses to viral infection.",2014 Oct 14,"['Aevermann, Brian D.', 'Pickett, Brett E.', 'Kumar, Sanjeev', 'Klem, Edward B.', 'Agnihothram, Sudhakar', 'Askovich, Peter S.', 'Bankhead, Armand', 'Bolles, Meagen', 'Carter, Victoria', 'Chang, Jean', 'Clauss, Therese R.W.', 'Dash, Pradyot', 'Diercks, Alan H.', 'Eisfeld, Amie J.', 'Ellis, Amy', 'Fan, Shufang', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Green, Richard R.', 'Gritsenko, Marina A.', 'Hatta, Masato', 'Heegel, Robert A.', 'Jacobs, Jon M.', 'Jeng, Sophia', 'Josset, Laurence', 'Kaiser, Shari M.', 'Kelly, Sara', 'Law, G. Lynn', 'Li, Chengjun', 'Li, Jiangning', 'Long, Casey', 'Luna, Maria L.', 'Matzke, Melissa', 'McDermott, Jason', 'Menachery, Vineet', 'Metz, Thomas O.', 'Mitchell, Hugh', 'Monroe, Matthew E.', 'Navarro, Garnet', 'Neumann, Gabriele', 'Podyminogin, Rebecca L.', 'Purvine, Samuel O.', 'Rosenberger, Carrie M.', 'Sanders, Catherine J.', 'Schepmoes, Athena A.', 'Shukla, Anil K.', 'Sims, Amy', 'Sova, Pavel', 'Tam, Vincent C.', 'Tchitchek, Nicolas', 'Thomas, Paul G.', 'Tilton, Susan C.', 'Totura, Allison', 'Wang, Jing', 'Webb-Robertson, Bobbie-Jo', 'Wen, Ji', 'Weiss, Jeffrey M.', 'Yang, Feng', 'Yount, Boyd', 'Zhang, Qibin', 'McWeeney, Shannon', 'Smith, Richard D.', 'Waters, Katrina M.', 'Kawaoka, Yoshihiro', 'Baric, Ralph', 'Aderem, Alan', 'Katze, Michael G.', 'Scheuermann, Richard H.']",Sci Data,,,True
d17d178051c8b4585dd66e5bd7133508b3bc2402,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,True
a60d8041651d988fe83f9d4def187dcec19e1b66,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
da3696f40f9fff27f4b2f2789526d6b0c81f899d,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
edc05633e04aec4493d6cb261f350e54391a2edb,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
94ebd991caf3c3fc8561d9ad165390c51fa67757,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
4891cafcdb90b9702d6081f319821128e5d368a0,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
9dcc65d991c6dc72487b7f9029097afad9f9d424,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
e7eb17bb7d285c2cbe084a2784f3d0decc05e9b7,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
db4b37fcb72b1a2aeaee7543840c6c5fd454867c,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
f03bbdf1292de07aefe78b58be581fabb2871325,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
affb6d09adb3ae7026f16be723735c1b0618e62f,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
b0e58214e1fcc36ae225b63fdaa85c3b98a2f0d0,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
e1363cfecc17035806dcf538c125b767cbc2da76,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
f764ceedc21a1f591bc92f09e46c3642483c556a,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
30dd652d4018a27fc531e9a9e9a17f154dea4431,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
1b77215769da2e43a11ea56da546a7fa6fcc9fe8,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
b0afa69f8bdf0d33afde64ae9ce1350e765e156c,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
abb2571a4c8f492dc552c761f076bbc2399d6fa1,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
4a79c933be9a09ed991368789689d63be064d038,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
165dd8a7bdeb7b18f7226a13ff23b8da2504c93d,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
b46a45f5875bb38ef2b8590cf7ae92e829eba5e4,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
f0cee74f65b4b34666a289e300164727a3da3ff4,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
5e8224da4332ec3b3998882fc55e494c9a695ede,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
ddbf31002935c6a62e177e3085670455ec4121ec,PMC,Progress and Challenges toward the Development of Vaccines against Avian Infectious Bronchitis,http://dx.doi.org/10.1155/2015/424860,PMC4411447,25954763,CC BY,"Avian infectious bronchitis (IB) is a widely distributed poultry disease that has huge economic impact on poultry industry. The continuous emergence of new IBV genotypes and lack of cross protection among different IBV genotypes have been an important challenge. Although live attenuated IB vaccines remarkably induce potent immune response, the potential risk of reversion to virulence, neutralization by the maternal antibodies, and recombination and mutation events are important concern on their usage. On the other hand, inactivated vaccines induce a weaker immune response and may require multiple dosing and/or the use of adjuvants that probably have potential safety risks and increased economic burdens. Consequently, alternative IB vaccines are widely sought. Recent advances in recombinant DNA technology have resulted in experimental IB vaccines that show promise in antibody and T-cells responses, comparable to live attenuated vaccines. Recombinant DNA vaccines have also been enhanced to target multiple serotypes and their efficacy has been improved using delivery vectors, nanoadjuvants, and in ovo vaccination approaches. Although most recombinant IB DNA vaccines are yet to be licensed, it is expected that these types of vaccines may hold sway as future vaccines for inducing a cross protection against multiple IBV serotypes.",2015 Apr 14,"['Bande, Faruku', 'Arshad, Siti Suri', 'Hair Bejo, Mohd', 'Moeini, Hassan', 'Omar, Abdul Rahman']",J Immunol Res,,,True
a4f3abb6d4a6463835878af8817389b825347d7b,PMC,"Influence of age, severity of infection, and co-infection on the duration of respiratory syncytial virus (RSV) shedding",http://dx.doi.org/10.1017/S0950268814001393,PMC4411640,24901443,CC BY,"RSV is the most important viral cause of pneumonia and bronchiolitis in children worldwide and has been associated with significant disease burden. With the renewed interest in RSV vaccines, we provide realistic estimates on duration, and influencing factors on RSV shedding which are required to better understand the impact of vaccination on the virus transmission dynamics. The data arise from a prospective study of 47 households (493 individuals) in rural Kenya, followed through a 6-month period of an RSV seasonal outbreak. Deep nasopharyngeal swabs were collected twice each week from all household members, irrespective of symptoms, and tested for RSV by multiplex PCR. The RSV G gene was sequenced. A total of 205 RSV infection episodes were detected in 179 individuals from 40 different households. The infection data were interval censored and assuming a random event time between observations, the average duration of virus shedding was 11·2 (95% confidence interval 10·1–12·3) days. The shedding durations were longer than previous estimates (3·9–7·4 days) based on immunofluorescence antigen detection or viral culture, and were shown to be strongly associated with age, severity of infection, and revealed potential interaction with other respiratory viruses. These findings are key to our understanding of the spread of this important virus and are relevant in the design of control programmes.",2015 Mar 5,"['MUNYWOKI, P. K.', 'KOECH, D. C.', 'AGOTI, C. N.', 'KIBIRIGE, N.', 'KIPKOECH, J.', 'CANE, P. A.', 'MEDLEY, G. F.', 'NOKES, D. J.']",Epidemiol Infect,,,True
73c2606bc45a573294360406628a8edd45bdd511,PMC,Use of linked electronic health records to assess mortality and length of stay associated with pandemic influenza A(H1N1)pdm09 at a UK teaching hospital,http://dx.doi.org/10.1017/S0950268814002076,PMC4411648,25119499,CC BY,"Effective use of data linkage is becoming an increasingly important focus in the new healthcare system in England. We linked data from the results of a multiplex PCR assay for respiratory viruses for a population of 230 inpatients at a UK teaching hospital with their patient administrative system records in order to compare the mortality and length of stay of patients who tested positive for influenza A(H1N1)pdm09 with those positive for another influenza A virus. The results indicated a reduced risk of death among influenza A(H1N1)pdm09 patients compared to other influenza A strains, with an adjusted risk ratio of 0·25 (95% confidence interval 0·08–0·75, P = 0·01), while no significant differences were found between the lengths of stay in the hospital for these two groups. Further development of such methods to link hospital data in a routine fashion could provide a rapid means of gaining epidemiological insights into emerging infectious diseases.",2015 Apr 14,"['Smith, C.', 'Curran, M. D.', 'Roddick, I.', 'Reacher, M.']",Epidemiol Infect,,,True
379317c0c8b61dd88b6faa235b21dd861436edcf,PMC,Incorporation of Spike and Membrane Glycoproteins into Coronavirus Virions,http://dx.doi.org/10.3390/v7041700,PMC4411675,25855243,CC BY,"The envelopes of coronaviruses (CoVs) contain primarily three proteins; the two major glycoproteins spike (S) and membrane (M), and envelope (E), a non-glycosylated protein. Unlike other enveloped viruses, CoVs bud and assemble at the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC). For efficient virion assembly, these proteins must be targeted to the budding site and to interact with each other or the ribonucleoprotein. Thus, the efficient incorporation of viral envelope proteins into CoV virions depends on protein trafficking and protein–protein interactions near the ERGIC. The goal of this review is to summarize recent findings on the mechanism of incorporation of the M and S glycoproteins into the CoV virion, focusing on protein trafficking and protein–protein interactions.",2015 Apr 3,"['Ujike, Makoto', 'Taguchi, Fumihiro']",Viruses,,,True
902ec7158906ac390bdc04cd55350a12c8a39281,PMC,The Evolution of Poxvirus Vaccines,http://dx.doi.org/10.3390/v7041726,PMC4411676,25853483,CC BY,"After Edward Jenner established human vaccination over 200 years ago, attenuated poxviruses became key players to contain the deadliest virus of its own family: Variola virus (VARV), the causative agent of smallpox. Cowpox virus (CPXV) and horsepox virus (HSPV) were extensively used to this end, passaged in cattle and humans until the appearance of vaccinia virus (VACV), which was used in the final campaigns aimed to eradicate the disease, an endeavor that was accomplished by the World Health Organization (WHO) in 1980. Ever since, naturally evolved strains used for vaccination were introduced into research laboratories where VACV and other poxviruses with improved safety profiles were generated. Recombinant DNA technology along with the DNA genome features of this virus family allowed the generation of vaccines against heterologous diseases, and the specific insertion and deletion of poxvirus genes generated an even broader spectrum of modified viruses with new properties that increase their immunogenicity and safety profile as vaccine vectors. In this review, we highlight the evolution of poxvirus vaccines, from first generation to the current status, pointing out how different vaccines have emerged and approaches that are being followed up in the development of more rational vaccines against a wide range of diseases.",2015 Apr 7,"['Sánchez-Sampedro, Lucas', 'Perdiguero, Beatriz', 'Mejías-Pérez, Ernesto', 'García-Arriaza, Juan', 'Di Pilato, Mauro', 'Esteban, Mariano']",Viruses,,,True
4271774baf0182630ce43862b9e0b151eda34e8c,PMC,"Insect-Specific Flaviviruses: A Systematic Review of Their Discovery, Host Range, Mode of Transmission, Superinfection Exclusion Potential and Genomic Organization",http://dx.doi.org/10.3390/v7041927,PMC4411683,25866904,CC BY,"There has been a dramatic increase in the number of insect-specific flaviviruses (ISFs) discovered in the last decade. Historically, these viruses have generated limited interest due to their inability to infect vertebrate cells. This viewpoint has changed in recent years because some ISFs have been shown to enhance or suppress the replication of medically important flaviviruses in co-infected mosquito cells. Additionally, comparative studies between ISFs and medically important flaviviruses can provide a unique perspective as to why some flaviviruses possess the ability to infect and cause devastating disease in humans while others do not. ISFs have been isolated exclusively from mosquitoes in nature but the detection of ISF-like sequences in sandflies and chironomids indicates that they may also infect other dipterans. ISFs can be divided into two distinct phylogenetic groups. The first group currently consists of approximately 12 viruses and includes cell fusing agent virus, Kamiti River virus and Culex flavivirus. These viruses are phylogenetically distinct from all other known flaviviruses. The second group, which is apparently not monophyletic, currently consists of nine viruses and includes Chaoyang virus, Nounané virus and Lammi virus. These viruses phylogenetically affiliate with mosquito/vertebrate flaviviruses despite their apparent insect-restricted phenotype. This article provides a review of the discovery, host range, mode of transmission, superinfection exclusion ability and genomic organization of ISFs. This article also attempts to clarify the ISF nomenclature because some of these viruses have been assigned more than one name due to their simultaneous discoveries by independent research groups.",2015 Apr 10,"['Blitvich, Bradley J.', 'Firth, Andrew E.']",Viruses,,,True
a4f9f7c80a7abba6f1d211cfd5b53ee14bb47000,PMC,Livestock trade networks for guiding animal health surveillance,http://dx.doi.org/10.1186/s12917-015-0354-4,PMC4411738,25889738,CC BY,"BACKGROUND: Trade in live animals can contribute to the introduction of exotic diseases, the maintenance and spread endemic diseases. Annually millions of animals are moved across Europe for the purposes of breeding, fattening and slaughter. Data on the number of animals moved were obtained from the Directorate General Sanco (DG Sanco) for 2011. These were converted to livestock units to enable direct comparison across species and their movements were mapped, used to calculate the indegrees and outdegrees of 27 European countries and the density and transitivity of movements within Europe. This provided the opportunity to discuss surveillance of European livestock movement taking into account stopping points en-route. RESULTS: High density and transitivity of movement for registered equines, breeding and fattening cattle, breeding poultry and pigs for breeding, fattening and slaughter indicates that hazards have the potential to spread quickly within these populations. This is of concern to highly connected countries particularly those where imported animals constitute a large proportion of their national livestock populations, and have a high indegree. The transport of poultry (older than 72 hours) and unweaned animals would require more rest breaks than the movement of weaned animals, which may provide more opportunities for disease transmission. Transitivity is greatest for animals transported for breeding purposes with cattle, pigs and poultry having values of over 50%. CONCLUSIONS: This paper demonstrated that some species (pigs and poultry) are traded much more frequently and at a larger scale than species such as goats. Some countries are more vulnerable than others due to importing animals from many countries, having imported animals requiring rest-breaks and importing large proportions of their national herd or flock. Such knowledge about the vulnerability of different livestock systems related to trade movements can be used to inform the design of animal health surveillance systems to facilitate the trade in animals between European member states. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0354-4) contains supplementary material, which is available to authorized users.",2015 Apr 1,"['Hardstaff, Jo L', 'Häsler, Barbara', 'Rushton, Jonathan R']",BMC Vet Res,,,False
4f7f915e27fdb16ed137f0b0738f865a53a54343,PMC,Livestock trade networks for guiding animal health surveillance,http://dx.doi.org/10.1186/s12917-015-0354-4,PMC4411738,25889738,CC BY,"BACKGROUND: Trade in live animals can contribute to the introduction of exotic diseases, the maintenance and spread endemic diseases. Annually millions of animals are moved across Europe for the purposes of breeding, fattening and slaughter. Data on the number of animals moved were obtained from the Directorate General Sanco (DG Sanco) for 2011. These were converted to livestock units to enable direct comparison across species and their movements were mapped, used to calculate the indegrees and outdegrees of 27 European countries and the density and transitivity of movements within Europe. This provided the opportunity to discuss surveillance of European livestock movement taking into account stopping points en-route. RESULTS: High density and transitivity of movement for registered equines, breeding and fattening cattle, breeding poultry and pigs for breeding, fattening and slaughter indicates that hazards have the potential to spread quickly within these populations. This is of concern to highly connected countries particularly those where imported animals constitute a large proportion of their national livestock populations, and have a high indegree. The transport of poultry (older than 72 hours) and unweaned animals would require more rest breaks than the movement of weaned animals, which may provide more opportunities for disease transmission. Transitivity is greatest for animals transported for breeding purposes with cattle, pigs and poultry having values of over 50%. CONCLUSIONS: This paper demonstrated that some species (pigs and poultry) are traded much more frequently and at a larger scale than species such as goats. Some countries are more vulnerable than others due to importing animals from many countries, having imported animals requiring rest-breaks and importing large proportions of their national herd or flock. Such knowledge about the vulnerability of different livestock systems related to trade movements can be used to inform the design of animal health surveillance systems to facilitate the trade in animals between European member states. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0354-4) contains supplementary material, which is available to authorized users.",2015 Apr 1,"['Hardstaff, Jo L', 'Häsler, Barbara', 'Rushton, Jonathan R']",BMC Vet Res,,,False
b5c63a3728bd54d804043f60a51594f39959b0e5,PMC,Livestock trade networks for guiding animal health surveillance,http://dx.doi.org/10.1186/s12917-015-0354-4,PMC4411738,25889738,CC BY,"BACKGROUND: Trade in live animals can contribute to the introduction of exotic diseases, the maintenance and spread endemic diseases. Annually millions of animals are moved across Europe for the purposes of breeding, fattening and slaughter. Data on the number of animals moved were obtained from the Directorate General Sanco (DG Sanco) for 2011. These were converted to livestock units to enable direct comparison across species and their movements were mapped, used to calculate the indegrees and outdegrees of 27 European countries and the density and transitivity of movements within Europe. This provided the opportunity to discuss surveillance of European livestock movement taking into account stopping points en-route. RESULTS: High density and transitivity of movement for registered equines, breeding and fattening cattle, breeding poultry and pigs for breeding, fattening and slaughter indicates that hazards have the potential to spread quickly within these populations. This is of concern to highly connected countries particularly those where imported animals constitute a large proportion of their national livestock populations, and have a high indegree. The transport of poultry (older than 72 hours) and unweaned animals would require more rest breaks than the movement of weaned animals, which may provide more opportunities for disease transmission. Transitivity is greatest for animals transported for breeding purposes with cattle, pigs and poultry having values of over 50%. CONCLUSIONS: This paper demonstrated that some species (pigs and poultry) are traded much more frequently and at a larger scale than species such as goats. Some countries are more vulnerable than others due to importing animals from many countries, having imported animals requiring rest-breaks and importing large proportions of their national herd or flock. Such knowledge about the vulnerability of different livestock systems related to trade movements can be used to inform the design of animal health surveillance systems to facilitate the trade in animals between European member states. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0354-4) contains supplementary material, which is available to authorized users.",2015 Apr 1,"['Hardstaff, Jo L', 'Häsler, Barbara', 'Rushton, Jonathan R']",BMC Vet Res,,,False
862715a714155bda6a996da96ed692ca426666a2,PMC,Livestock trade networks for guiding animal health surveillance,http://dx.doi.org/10.1186/s12917-015-0354-4,PMC4411738,25889738,CC BY,"BACKGROUND: Trade in live animals can contribute to the introduction of exotic diseases, the maintenance and spread endemic diseases. Annually millions of animals are moved across Europe for the purposes of breeding, fattening and slaughter. Data on the number of animals moved were obtained from the Directorate General Sanco (DG Sanco) for 2011. These were converted to livestock units to enable direct comparison across species and their movements were mapped, used to calculate the indegrees and outdegrees of 27 European countries and the density and transitivity of movements within Europe. This provided the opportunity to discuss surveillance of European livestock movement taking into account stopping points en-route. RESULTS: High density and transitivity of movement for registered equines, breeding and fattening cattle, breeding poultry and pigs for breeding, fattening and slaughter indicates that hazards have the potential to spread quickly within these populations. This is of concern to highly connected countries particularly those where imported animals constitute a large proportion of their national livestock populations, and have a high indegree. The transport of poultry (older than 72 hours) and unweaned animals would require more rest breaks than the movement of weaned animals, which may provide more opportunities for disease transmission. Transitivity is greatest for animals transported for breeding purposes with cattle, pigs and poultry having values of over 50%. CONCLUSIONS: This paper demonstrated that some species (pigs and poultry) are traded much more frequently and at a larger scale than species such as goats. Some countries are more vulnerable than others due to importing animals from many countries, having imported animals requiring rest-breaks and importing large proportions of their national herd or flock. Such knowledge about the vulnerability of different livestock systems related to trade movements can be used to inform the design of animal health surveillance systems to facilitate the trade in animals between European member states. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0354-4) contains supplementary material, which is available to authorized users.",2015 Apr 1,"['Hardstaff, Jo L', 'Häsler, Barbara', 'Rushton, Jonathan R']",BMC Vet Res,,,False
2cedf6edf59b93290a68074986ee680c8c8e89a1,PMC,Livestock trade networks for guiding animal health surveillance,http://dx.doi.org/10.1186/s12917-015-0354-4,PMC4411738,25889738,CC BY,"BACKGROUND: Trade in live animals can contribute to the introduction of exotic diseases, the maintenance and spread endemic diseases. Annually millions of animals are moved across Europe for the purposes of breeding, fattening and slaughter. Data on the number of animals moved were obtained from the Directorate General Sanco (DG Sanco) for 2011. These were converted to livestock units to enable direct comparison across species and their movements were mapped, used to calculate the indegrees and outdegrees of 27 European countries and the density and transitivity of movements within Europe. This provided the opportunity to discuss surveillance of European livestock movement taking into account stopping points en-route. RESULTS: High density and transitivity of movement for registered equines, breeding and fattening cattle, breeding poultry and pigs for breeding, fattening and slaughter indicates that hazards have the potential to spread quickly within these populations. This is of concern to highly connected countries particularly those where imported animals constitute a large proportion of their national livestock populations, and have a high indegree. The transport of poultry (older than 72 hours) and unweaned animals would require more rest breaks than the movement of weaned animals, which may provide more opportunities for disease transmission. Transitivity is greatest for animals transported for breeding purposes with cattle, pigs and poultry having values of over 50%. CONCLUSIONS: This paper demonstrated that some species (pigs and poultry) are traded much more frequently and at a larger scale than species such as goats. Some countries are more vulnerable than others due to importing animals from many countries, having imported animals requiring rest-breaks and importing large proportions of their national herd or flock. Such knowledge about the vulnerability of different livestock systems related to trade movements can be used to inform the design of animal health surveillance systems to facilitate the trade in animals between European member states. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0354-4) contains supplementary material, which is available to authorized users.",2015 Apr 1,"['Hardstaff, Jo L', 'Häsler, Barbara', 'Rushton, Jonathan R']",BMC Vet Res,,,True
03fa4232b3fbc44b6029d52c3120f4e82fdc49c0,PMC,Human coronavirus OC43 3CL protease and the potential of ML188 as a broad-spectrum lead compound: Homology modelling and molecular dynamic studies,http://dx.doi.org/10.1186/s12900-015-0035-3,PMC4411765,25928480,CC BY,"BACKGROUND: The coronavirus 3 chymotrypsin-like protease (3CL(pro)) is a validated target in the design of potential anticoronavirus inhibitors. The high degree of homology within the protease’s active site and substrate conservation supports the identification of broad spectrum lead compounds. A previous study identified the compound ML188, also termed 16R, as an inhibitor of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) 3CL(pro). This study will detail the generation of a homology model of the 3CL(pro) of the human coronavirus OC43 and determine the potential of 16R to form a broad-spectrum lead compound. MODELLER was used to generate a suitable three-dimensional model of the OC43 3CL(pro) and the Prime module of Schrӧdinger predicted the binding conformation and free energy of binding of 16R within the 3CL(pro) active site. Molecular dynamics further confirmed ligand stability and hydrogen bonding networks. RESULTS: A high quality homology model of the OC43 3CL(pro) was successfully generated in an active conformation. Further studies reproduced the binding pose of 16R within the active site of the generated model, where its free energy of binding was shown to equal that of the 3CL(pro) of SARS-CoV, a receptor it is experimentally proven to inhibit. The stability of the ligand was subsequently confirmed by molecular dynamics. CONCLUSION: The lead compound 16R may represent a broad-spectrum inhibitor of the 3CL(pro) of OC43 and potentially other coronaviruses. This study provides an atomistic structure of the 3CL(pro) of OC43 and supports further experimental validation of the inhibitory effects of 16R. These findings further confirm that the 3CL(pro) of coronaviruses can be inhibited by broad spectrum lead compounds.",2015 Apr 28,"['Berry, Michael', 'Fielding, Burtram', 'Gamieldien, Junaid']",BMC Struct Biol,,,True
9d089a2632f7a6fc75d5e723ebe2ac9db15c0048,PMC,CD200 Receptor Restriction of Myeloid Cell Responses Antagonizes Antiviral Immunity and Facilitates Cytomegalovirus Persistence within Mucosal Tissue,http://dx.doi.org/10.1371/journal.ppat.1004641,PMC4412112,25654642,CC BY,"CD200 receptor (CD200R) negatively regulates peripheral and mucosal innate immune responses. Viruses, including herpesviruses, have acquired functional CD200 orthologs, implying that viral exploitation of this pathway is evolutionary advantageous. However, the role that CD200R signaling plays during herpesvirus infection in vivo requires clarification. Utilizing the murine cytomegalovirus (MCMV) model, we demonstrate that CD200R facilitates virus persistence within mucosal tissue. Specifically, MCMV infection of CD200R-deficient mice (CD200R(-/-)) elicited heightened mucosal virus-specific CD4 T cell responses that restricted virus persistence in the salivary glands. CD200R did not directly inhibit lymphocyte effector function. Instead, CD200R(-/-) mice exhibited enhanced APC accumulation that in the mucosa was a consequence of elevated cellular proliferation. Although MCMV does not encode an obvious CD200 homolog, productive replication in macrophages induced expression of cellular CD200. CD200 from hematopoietic and non-hematopoietic cells contributed independently to suppression of antiviral control in vivo. These results highlight the CD200-CD200R pathway as an important regulator of antiviral immunity during cytomegalovirus infection that is exploited by MCMV to establish chronicity within mucosal tissue.",2015 Feb 5,"['Stack, Gabrielle', 'Jones, Emma', 'Marsden, Morgan', 'Stacey, Maria A.', 'Snelgrove, Robert J.', 'Lacaze, Paul', 'Jacques, Laura C.', 'Cuff, Simone M.', 'Stanton, Richard J.', 'Gallimore, Awen M.', 'Hussell, Tracy', 'Wilkinson, Gavin W. G.', 'Ghazal, Peter', 'Taylor, Philip R.', 'Humphreys, Ian R.']",PLoS Pathog,,,True
4eca3df95a8bf82f07ba51b6978bd4049f8df827,PMC,Laboratory Investigation and Phylogenetic Analysis of an Imported Middle East Respiratory Syndrome Coronavirus Case in Greece,http://dx.doi.org/10.1371/journal.pone.0125809,PMC4412533,25919137,CC0,"Rapid and reliable laboratory diagnosis of persons suspected of Middle East respiratory syndrome coronavirus (MERS-CoV) infection is important for timely implementation of infection control practices and disease management. In addition, monitoring molecular changes in the virus can help elucidate chains of transmission and identify mutations that might influence virus transmission efficiency. This was illustrated by a recent laboratory investigation we conducted on an imported MERS-CoV case in Greece. Two oropharyngeal swab specimens were collected on the 1(st) and 2(nd) day of patient hospitalization and tested using two real-time RT-PCR (rRT-PCR) assays targeting the UpE and Orf-1a regions of the MERS-CoV genome and RT-PCR and partial sequencing of RNA-dependent RNA polymerase and nucleocapsid genes. Serum specimens were also collected and serological test were performed. Results from the first swab sample were inconclusive while the second swab was strongly positive for MERS-CoV RNA by rRT-PCR and confirmed positive by RT-PCR and partial gene sequencing. Positive serologic test results further confirmed MERS-CoV infection. Full-length nucleocapsid and spike gene coding sequences were later obtained from the positive swab sample. Phylogenetic analysis revealed that the virus was closely related to recent human-derived MERS-CoV strains obtained in Jeddah and Makkah, Saudi Arabia, in April 2014 and dromedary camels in Saudi Arabia and Qatar. These findings were consistent with the patient’s history. We also identified a unique amino acid substitution in the spike receptor binding domain that may have implications for receptor binding efficiency. Our initial inconclusive rRT-PCR results highlight the importance of collecting multiple specimens from suspect MERS-CoV cases and particularly specimens from the lower respiratory tract.",2015 Apr 28,"['Kossyvakis, Athanasios', 'Tao, Ying', 'Lu, Xiaoyan', 'Pogka, Vasiliki', 'Tsiodras, Sotirios', 'Emmanouil, Mary', 'Mentis, Andreas F.', 'Tong, Suxiang', 'Erdman, Dean D.', 'Antoniadis, Antonios']",PLoS One,,,True
6bd542932368c6d6a32847714e3327136f3c4bd8,PMC,Pseudotype-Based Neutralization Assays for Influenza: A Systematic Analysis,http://dx.doi.org/10.3389/fimmu.2015.00161,PMC4413832,25972865,CC BY,"The use of vaccination against the influenza virus remains the most effective method of mitigating the significant morbidity and mortality caused by this virus. Antibodies elicited by currently licensed influenza vaccines are predominantly hemagglutination-inhibition (HI)-competent antibodies that target the globular head of hemagglutinin (HA) thus inhibiting influenza virus entry into target cells. These antibodies predominantly confer homosubtypic/strain specific protection and only rarely confer heterosubtypic protection. However, recent academia or pharma-led R&D toward the production of a “universal vaccine” has centered on the elicitation of antibodies directed against the stalk of the influenza HA that has been shown to confer broad protection across a range of different subtypes (H1–H16). The accurate and sensitive measurement of antibody responses elicited by these “next-generation” influenza vaccines is, however, hampered by the lack of sensitivity of the traditional influenza serological assays HI, single radial hemolysis, and microneutralization. Assays utilizing pseudotypes, chimeric viruses bearing influenza glycoproteins, have been shown to be highly efficient for the measurement of homosubtypic and heterosubtypic broadly neutralizing antibodies, making them ideal serological tools for the study of cross-protective responses against multiple influenza subtypes with pandemic potential. In this review, we will analyze and compare literature involving the production of influenza pseudotypes with particular emphasis on their use in serum antibody neutralization assays. This will enable us to establish the parameters required for optimization and propose a consensus protocol to be employed for the further deployment of these assays in influenza vaccine immunogenicity studies.",2015 Apr 29,"['Carnell, George William', 'Ferrara, Francesca', 'Grehan, Keith', 'Thompson, Craig Peter', 'Temperton, Nigel James']",Front Immunol,,,True
65dad274ae49f213826f7cb5c43415778e053ce0,PMC,Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD,http://dx.doi.org/10.1038/srep09927,PMC4413879,25923474,CC BY,"Daily oscillations of pulmonary function depend on the rhythmic activity of the circadian timing system. Environmental tobacco/cigarette smoke (CS) disrupts circadian clock leading to enhanced inflammatory responses. Infection with influenza A virus (IAV) increases hospitalization rates and death in susceptible individuals, including patients with Chronic Obstructive Pulmonary Disease (COPD). We hypothesized that molecular clock disruption is enhanced by IAV infection, altering cellular and lung function, leading to severity in airway disease phenotypes. C57BL/6J mice exposed to chronic CS, BMAL1 knockout (KO) mice and wild-type littermates were infected with IAV. Following infection, we measured diurnal rhythms of clock gene expression in the lung, locomotor activity, pulmonary function, inflammatory, pro-fibrotic and emphysematous responses. Chronic CS exposure combined with IAV infection altered the timing of clock gene expression and reduced locomotor activity in parallel with increased lung inflammation, disrupted rhythms of pulmonary function, and emphysema. BMAL1 KO mice infected with IAV showed pronounced detriments in behavior and survival, and increased lung inflammatory and pro-fibrotic responses. This suggests that remodeling of lung clock function following IAV infection alters clock-dependent gene expression and normal rhythms of lung function, enhanced emphysematous and injurious responses. This may have implications for the pathobiology of respiratory virus-induced airway disease severity and exacerbations.",2015 Apr 29,"['Sundar, Isaac K.', 'Ahmad, Tanveer', 'Yao, Hongwei', 'Hwang, Jae-woong', 'Gerloff, Janice', 'Lawrence, B. Paige', 'Sellix, Michael T.', 'Rahman, Irfan']",Sci Rep,,,True
ae6773868c2850e5c8b8177735b19d01341a53b6,PMC,Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD,http://dx.doi.org/10.1038/srep09927,PMC4413879,25923474,CC BY,"Daily oscillations of pulmonary function depend on the rhythmic activity of the circadian timing system. Environmental tobacco/cigarette smoke (CS) disrupts circadian clock leading to enhanced inflammatory responses. Infection with influenza A virus (IAV) increases hospitalization rates and death in susceptible individuals, including patients with Chronic Obstructive Pulmonary Disease (COPD). We hypothesized that molecular clock disruption is enhanced by IAV infection, altering cellular and lung function, leading to severity in airway disease phenotypes. C57BL/6J mice exposed to chronic CS, BMAL1 knockout (KO) mice and wild-type littermates were infected with IAV. Following infection, we measured diurnal rhythms of clock gene expression in the lung, locomotor activity, pulmonary function, inflammatory, pro-fibrotic and emphysematous responses. Chronic CS exposure combined with IAV infection altered the timing of clock gene expression and reduced locomotor activity in parallel with increased lung inflammation, disrupted rhythms of pulmonary function, and emphysema. BMAL1 KO mice infected with IAV showed pronounced detriments in behavior and survival, and increased lung inflammatory and pro-fibrotic responses. This suggests that remodeling of lung clock function following IAV infection alters clock-dependent gene expression and normal rhythms of lung function, enhanced emphysematous and injurious responses. This may have implications for the pathobiology of respiratory virus-induced airway disease severity and exacerbations.",2015 Apr 29,"['Sundar, Isaac K.', 'Ahmad, Tanveer', 'Yao, Hongwei', 'Hwang, Jae-woong', 'Gerloff, Janice', 'Lawrence, B. Paige', 'Sellix, Michael T.', 'Rahman, Irfan']",Sci Rep,,,False
98e35a687137cb2b91458118347ad93f7ad188fb,PMC,A Human Monoclonal Antibody against Hepatitis B Surface Antigen with Potent Neutralizing Activity,http://dx.doi.org/10.1371/journal.pone.0125704,PMC4414269,25923526,CC BY,"We describe the production and characterization of human monoclonal antibodies (mAb) specific for the major hepatitis B virus (HBV) S protein. The mAbs, two IgG1κ and one IgG1λ, were secreted by B-cell clones obtained from peripheral blood mononuclear cells (PBMC) of one person convalescent from acute hepatitis B and one vaccinated individual. The former recognized a denaturation-insensitive epitope within the p24 protein whereas the latter recognized a denaturation-sensitive, conformational epitope located within the HBsAg common “a” determinant. This mAb, denominated ADRI-2F3, displayed a very high protective titer of over 43,000 IU/mg mAb and showed an extremely potent neutralizing activity in the in vitro model of HBV infection using primary hepatocytes from Tupaia belangeri as target. Recombinant variable heavy and light domain sequences derived from mAb ADRI-2F3 were cloned into eukaryotic expression vectors and showed identical fine specificity and 1 log(10) higher titer than the original IgG1λ. It is envisaged that such mAb will be able to efficiently prevent HBV reinfection after liver transplantation for end-stage chronic HBV infection or infection after needle-stick exposure, providing an unlimited source of valuable protective anti-HBs antibody.",2015 Apr 29,"['Cerino, Antonella', 'Bremer, Corinna M.', 'Glebe, Dieter', 'Mondelli, Mario U.']",PLoS One,,,True
bc558b5af5c0e23264cc177d3c0622a8726deb2e,PMC,Resolution of the cellular proteome of the nucleocapsid protein from a highly pathogenic isolate of porcine reproductive and respiratory syndrome virus identifies PARP-1 as a cellular target whose interaction is critical for virus biology,http://dx.doi.org/10.1016/j.vetmic.2014.11.023,PMC4414928,25614100,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to the swine industry and food security worldwide. The nucleocapsid (N) protein is a major structural protein of PRRSV. The primary function of this protein is to encapsidate the viral RNA genome, and it is also thought to participate in the modulation of host cell biology and recruitment of cellular factors to facilitate virus infection. In order to the better understand these latter roles the cellular interactome of PRRSV N protein was defined using label free quantitative proteomics. This identified several cellular factors that could interact with the N protein including poly [ADP-ribose] polymerase 1 (PARP-1), a cellular protein, which can add adenosine diphosphate ribose to a protein. Use of the PARP-1 small molecule inhibitor, 3-AB, in PRRSV infected cells demonstrated that PARP-1 was required and acted as an enhancer factor for virus biology. Serial growth of PRRSV in different concentrations of 3-AB did not yield viruses that were able to grow with wild type kinetics, suggesting that by targeting a cellular protein crucial for virus biology, resistant phenotypes did not emerge. This study provides further evidence that cellular proteins, which are critical for virus biology, can also be targeted to ablate virus growth and provide a high barrier for the emergence of drug resistance.",2015 Mar 23,"['Liu, Long', 'Lear, Zoe', 'Hughes, David J.', 'Wu, Weining', 'Zhou, En-min', 'Whitehouse, Adrian', 'Chen, Hongying', 'Hiscox, Julian A.']",Vet Microbiol,,,False
57175f1b43951c500b3fe6cb678824ea9e6d8ae2,PMC,The evidence base of primary research in public health emergency preparedness: a scoping review and stakeholder consultation,http://dx.doi.org/10.1186/s12889-015-1750-1,PMC4415223,25925775,CC BY,"BACKGROUND: Effective public health emergency preparedness and response systems are important in mitigating the impact of all-hazards emergencies on population health. The evidence base for public health emergency preparedness (PHEP) is weak, however, and previous reviews have noted a substantial proportion of anecdotal event reports. To investigate the body of research excluding the anecdotal reports and better understand primary and analytical research for PHEP, a scoping review was conducted with two objectives: first, to develop a thematic map focused on primary research; and second, to use this map to inform and guide an understanding of knowledge gaps relevant to research and practice in PHEP. METHODS: A scoping review was conducted based on established methodology. Multiple databases of indexed and grey literature were searched based on concepts of public health, emergency, emergency management/preparedness and evaluation/evidence. Inclusion and exclusion criteria were applied iteratively. Primary research studies that were evidence-based or evaluative in nature were included in the final group of selected studies. Thematic analysis was conducted for this group. Stakeholder consultation was undertaken for the purpose of validating themes and identifying knowledge gaps. To accomplish this, a purposive sample of researchers and practicing professionals in PHEP or closely related fields was asked to complete an online survey and participate in an in-person meeting. Final themes and knowledge gaps were synthesized after stakeholder consultation. RESULTS: Database searching yielded 3015 citations and article selection resulted in a final group of 58 articles. A list of ten themes from this group of articles was disseminated to stakeholders with the survey questions. Survey findings resulted in four cross-cutting themes and twelve stand-alone themes. Several key knowledge gaps were identified in the following themes: attitudes and beliefs; collaboration and system integration; communication; quality improvement and performance standards; and resilience. Resilience emerged as both a gap and a cross-cutting theme. Additional cross-cutting themes included equity, gender considerations, and high risk or at-risk populations. CONCLUSIONS: In this scoping review of the literature enhanced by stakeholder consultation, key themes and knowledge gaps in the PHEP evidence base were identified which can be used to inform future practice-oriented research in PHEP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-1750-1) contains supplementary material, which is available to authorized users.",2015 Apr 28,"['Khan, Yasmin', 'Fazli, Ghazal', 'Henry, Bonnie', 'de Villa, Eileen', 'Tsamis, Charoula', 'Grant, Moira', 'Schwartz, Brian']",BMC Public Health,,,True
d15dcc8f6d6ca39f7d43a8673ba44b0f0c53e449,PMC,From the Editor's desk,http://dx.doi.org/10.1111/irv.12311,PMC4415693,25824028,CC BY,,2015 May 23,"Nguyen-Van-Tam, Jonathan S",Influenza Other Respir Viruses,,,True
8cf5055e0ca001204109a5455b58a42aaa79f431,PMC,Healthcare workers' willingness to work during an influenza pandemic: a systematic review and meta-analysis,http://dx.doi.org/10.1111/irv.12310,PMC4415696,25807865,CC BY,"To estimate the proportion of healthcare workers (HCWs) willing to work during an influenza pandemic and identify associated risk factors, we undertook a systematic review and meta-analysis compliant with PRISMA guidance. Databases and grey literature were searched to April 2013, and records were screened against protocol eligibility criteria. Data extraction and risk of bias assessments were undertaken using a piloted form. Random-effects meta-analyses estimated (i) pooled proportion of HCWs willing to work and (ii) pooled odds ratios of risk factors associated with willingness to work. Heterogeneity was quantified using the I(2) statistic, and publication bias was assessed using funnel plots and Egger's test. Data were synthesized narratively where meta-analyses were not possible. Forty-three studies met our inclusion criteria. Meta-analysis of the proportion of HCWs willing to work was abandoned due to excessive heterogeneity (I(2) = 99·2%). Narrative synthesis showed study estimates ranged from 23·1% to 95·8% willingness to work, depending on context. Meta-analyses of specific factors showed that male HCWs, physicians and nurses, full-time employment, perceived personal safety, awareness of pandemic risk and clinical knowledge of influenza pandemics, role-specific knowledge, pandemic response training, and confidence in personal skills were statistically significantly associated with increased willingness. Childcare obligations were significantly associated with decreased willingness. HCWs' willingness to work during an influenza pandemic was moderately high, albeit highly variable. Numerous risk factors showed a statistically significant association with willingness to work despite significant heterogeneity between studies. None of the included studies were based on appropriate theoretical constructs of population behaviour.",2015 May 23,"['Aoyagi, Yumiko', 'Beck, Charles R', 'Dingwall, Robert', 'Nguyen-Van-Tam, Jonathan S']",Influenza Other Respir Viruses,,,True
fd31ade73c720f893a5ddb2370df90a84511ec4a,PMC,"Distribution of antibodies against influenza virus in pigs from farrow-to-finish farms in Minas Gerais state, Brazil",http://dx.doi.org/10.1111/irv.12304,PMC4415701,25648743,CC BY,"BACKGROUND: Swine influenza virus (SIV) is the cause of an acute respiratory disease that affects swine worldwide. In Brazil, SIV has been identified in pigs since 1978. After the emergence of pandemic H1N1 in 2009 (H1N1pdm09), few studies reported the presence of influenza virus in Brazilian herds. OBJECTIVES: The objective of this study was to evaluate the serological profile for influenza virus in farrow-to-finish pig farms in Minas Gerais state, Brazil. METHODS: Thirty farms with no SIV vaccination history were selected from the four larger pig production areas in Minas Gerais state (Zona da Mata, Triângulo Mineiro/Alto Paranaíba, South/Southwest and the Belo Horizonte metropolitan area). At each farm, blood samples were randomly collected from 20 animals in each production cycle category: breeding animals (sows and gilts), farrowing crate (2–3 weeks), nursery (4–7 weeks), grower pigs (8–14 weeks), and finishing pigs (15–16 weeks), with 100 samples per farm and a total of 3000 animals in this study. The samples were tested for hemagglutination inhibition activity against H1N1 pandemic strain (A/swine/Brazil/11/2009) and H3N2 SIV (A/swine/Iowa/8548-2/98) reference strain. RESULTS: The percentages of seropositive animals for H1N1pdm09 and H3N2 were 26·23% and 1·57%, respectively, and the percentages of seropositive herds for both viruses were 96·6% and 13·2%, respectively. CONCLUSIONS: The serological profiles differed for both viruses and among the studied areas, suggesting a high variety of virus circulation around the state, as well as the presence of seronegative animals susceptible to influenza infection and, consequently, new respiratory disease outbreaks.",2015 May 23,"['Dias, Alessandra S', 'Costa, Érica A', 'Rajão, Daniela S', 'Guedes, Roberto M C', 'Ciacci Zanella, Janice R', 'Lobato, Zélia I P']",Influenza Other Respir Viruses,,,True
2bf3f075175c307923fc400707b30616a676419c,PMC,The Ubiquitin Proteasome System Plays a Role in Venezuelan Equine Encephalitis Virus Infection,http://dx.doi.org/10.1371/journal.pone.0124792,PMC4415917,25927990,CC BY,"Many viruses have been implicated in utilizing or modulating the Ubiquitin Proteasome System (UPS) to enhance viral multiplication and/or to sustain a persistent infection. The mosquito-borne Venezuelan equine encephalitis virus (VEEV) belongs to the Togaviridae family and is an important biodefense pathogen and select agent. There are currently no approved vaccines or therapies for VEEV infections; therefore, it is imperative to identify novel targets for therapeutic development. We hypothesized that a functional UPS is required for efficient VEEV multiplication. We have shown that at non-toxic concentrations Bortezomib, a FDA-approved inhibitor of the proteasome, proved to be a potent inhibitor of VEEV multiplication in the human astrocytoma cell line U87MG. Bortezomib inhibited the virulent Trinidad donkey (TrD) strain and the attenuated TC-83 strain of VEEV. Additional studies with virulent strains of Eastern equine encephalitis virus (EEEV) and Western equine encephalitis virus (WEEV) demonstrated that Bortezomib is a broad spectrum inhibitor of the New World alphaviruses. Time-of-addition assays showed that Bortezomib was an effective inhibitor of viral multiplication even when the drug was introduced many hours post exposure to the virus. Mass spectrometry analyses indicated that the VEEV capsid protein is ubiquitinated in infected cells, which was validated by confocal microscopy and immunoprecipitation assays. Subsequent studies revealed that capsid is ubiquitinated on K48 during early stages of infection which was affected by Bortezomib treatment. This study will aid future investigations in identifying host proteins as potential broad spectrum therapeutic targets for treating alphavirus infections.",2015 Apr 30,"['Amaya, Moushimi', 'Keck, Forrest', 'Lindquist, Michael', 'Voss, Kelsey', 'Scavone, Lauren', 'Kehn-Hall, Kylene', 'Roberts, Brian', 'Bailey, Charles', 'Schmaljohn, Connie', 'Narayanan, Aarthi']",PLoS One,,,True
3025f11897040ad8046b2a7ef8e94fc8615df214,PMC,"Impact of the 2009 H1N1 Pandemic on Age-Specific Epidemic Curves of Other Respiratory Viruses: A Comparison of Pre-Pandemic, Pandemic and Post-Pandemic Periods in a Subtropical City",http://dx.doi.org/10.1371/journal.pone.0125447,PMC4416050,25928217,CC BY,"BACKGROUND: The 2009 H1N1 influenza pandemic caused offseason peaks in temperate regions but coincided with the summer epidemic of seasonal influenza and other common respiratory viruses in subtropical Hong Kong. This study was aimed to investigate the impact of the pandemic on age-specific epidemic curves of other respiratory viruses. METHODS: Weekly laboratory-confirmed cases of influenza A (subtypes seasonal A(H1N1), A(H3N2), pandemic virus A(H1N1)pdm09), influenza B, respiratory syncytial virus (RSV), adenovirus and parainfluenza were obtained from 2004 to 2013. Age-specific epidemic curves of viruses other than A(H1N1)pdm09 were compared between the pre-pandemic (May 2004 – April 2009), pandemic (May 2009 – April 2010) and post-pandemic periods (May 2010 – April 2013). RESULTS: There were two peaks of A(H1N1)pdm09 in Hong Kong, the first in September 2009 and the second in February 2011. The infection rate was found highest in young children in both waves, but markedly fewer cases in school children were recorded in the second wave than in the first wave. Positive proportions of viruses other than A(H1N1)pdm09 markedly decreased in all age groups during the first pandemic wave. After the first wave of the pandemic, the positive proportion of A(H3N2) increased, but those of B and RSV remained slightly lower than their pre-pandemic proportions. Changes in seasonal pattern and epidemic peak time were also observed, but inconsistent across virus-age groups. CONCLUSION: Our findings provide some evidence that age distribution, seasonal pattern and peak time of other respiratory viruses have changed since the pandemic. These changes could be the result of immune interference and changing health seeking behavior, but the mechanism behind still needs further investigations.",2015 Apr 30,"['Yang, Lin', 'Chan, Kwok Hung', 'Suen, Lorna K. P.', 'Chan, King Pan', 'Wang, Xiling', 'Cao, Peihua', 'He, Daihai', 'Peiris, J. S. Malik', 'Wong, Chit Ming']",PLoS One,,,True
bc67c021d6e189215a0101f6e5de32daa8e4ccee,PMC,Diversity of coronavirus in bats from Eastern Thailand,http://dx.doi.org/10.1186/s12985-015-0289-1,PMC4416284,25884446,CC BY,"BACKGROUND: Bats are reservoirs for a diverse range of coronaviruses (CoVs), including those closely related to human pathogens such as Severe Acute Respiratory Syndrome (SARS) CoV and Middle East Respiratory Syndrome CoV. There are approximately 139 bat species reported to date in Thailand, of which two are endemic species. Due to the zoonotic potential of CoVs, standardized surveillance efforts to characterize viral diversity in wildlife are imperative. FINDINGS: A total of 626 bats from 19 different bat species were individually sampled from 5 provinces in Eastern Thailand between 2008 and 2013 (84 fecal and 542 rectal swabs). Samples collected (either fresh feces or rectal swabs) were placed directly into RNA stabilization reagent, transported on ice within 24 hours and preserved at −80°C until further analysis. CoV RNA was detected in 47 specimens (7.6%), from 13 different bat species, using broadly reactive consensus PCR primers targeting the RNA-Dependent RNA Polymerase gene designed to detect all CoVs. Thirty seven alphacoronaviruses, nine lineage D betacoronaviruses, and one lineage B betacoronavirus (SARS-CoV related) were identified. Six new bat CoV reservoirs were identified in our study, namely Cynopterus sphinx, Taphozous melanopogon, Hipposideros lekaguli, Rhinolophus shameli, Scotophilus heathii and Megaderma lyra. CONCLUSIONS: CoVs from the same genetic lineage were found in different bat species roosting in similar or different locations. These data suggest that bat CoV lineages are not strictly concordant with their hosts. Our phylogenetic data indicates high diversity and a complex ecology of CoVs in bats sampled from specific areas in eastern regions of Thailand. Further characterization of additional CoV genes may be useful to better describe the CoV divergence.",2015 Apr 11,"['Wacharapluesadee, Supaporn', 'Duengkae, Prateep', 'Rodpan, Apaporn', 'Kaewpom, Thongchai', 'Maneeorn, Patarapol', 'Kanchanasaka, Budsabong', 'Yingsakmongkon, Sangchai', 'Sittidetboripat, Nuntaporn', 'Chareesaen, Chaiyaporn', 'Khlangsap, Nathawat', 'Pidthong, Apisit', 'Leadprathom, Kumron', 'Ghai, Siriporn', 'Epstein, Jonathan H', 'Daszak, Peter', 'Olival, Kevin J', 'Blair, Patrick J', 'Callahan, Michael V', 'Hemachudha, Thiravat']",Virol J,,,True
27636c830ab9c45d38454d50312227747652f70e,PMC,Differential expression of miRNAs in enterovirus 71-infected cells,http://dx.doi.org/10.1186/s12985-015-0288-2,PMC4416288,25889836,CC BY,"BACKGROUND: Enterovirus 71 (EV71) is one of the major etiological pathogens of hand, foot and mouth disease (HFMD) and can cause severe cerebral and pulmonary complications and even fatality. MicroRNAs (miRNAs), a class of small non-coding RNA molecules, play an important role in post-transcriptional regulation of gene expression and thereby influencing various physiological and pathological processes. Increasing evidence suggests that miRNAs act as key effector molecules in the complicated pathogen-host interactions. However, the roles of miRNAs in EV71 infection and pathogenesis are not well understood. METHODS: To identify special miRNAs involved in EV71 infection, a microarray assay was performed to study the expression pattern of miRNAs in EV71-infected human rhabdomyosarcoma cells (RD cells) and uninfected RD cells. We further predicted the putative target genes for the dysregulated miRNAs using the online bioinformatic algorithms (TargetScan, miRanda and PicTar) and carried out functional annotation including GO enrichment and KEGG pathway analysis for miRNA predicted targets. Then, the results of microarray were further confirmed by quantitative RT-PCR. RESULTS: Totally, 45 differentially expressed miRNAs ware identified by microarray, among which 36 miRNAs were up-regulated and 9 were down-regulated. 7166 predicted target genes for the dysregulated miRNAs were revealed by using TargetScan in conjunction with miRanda and PicTar. The GO annotation suggested that predicted targets of miRNAs were enriched into the category of signal transduction, regulation of transcription, metabolic process, protein phosphorylation, apoptotic process and immune response. KEGG pathway analysis suggested that these predicted target genes were involved in many important pathways, mainly including endocytosis and focal adhesion, MAPK signaling pathway, hypertrophic cardiomyopathy, melanogenesis and ErbB signaling pathway. The expression levels of 8 most differentially up-regulated miRNAs and 3 most differentially down-regulated miRNAs were confirmed by qRT-PCR. The expressions of hsa-miR-4530, hsa-miR-4492, hsa-miR-6125, hsa-miR-494-3p, hsa-miR-638, hsa-miR-6743-5p, hsa-miR-4459 and hsa-miR-4443 detected by qRT-PCR were consistent with the microarray data. CONCLUSION: These results might extend our understanding to the regulatory mechanism of miRNAs underlying the pathogenesis of EV71 infection, thus strengthening the preventative and therapeutic strategies of HFMD caused by EV71.",2015 Apr 10,"['Xun, Meng', 'Ma, Chao-Feng', 'Du, Quan-Li', 'Ji, Yan-Hong', 'Xu, Ji-Ru']",Virol J,,,True
87620b2fa94ff9b59a3a84382dceae62f83259a6,PMC,Postnatal Persistent Infection with Classical Swine Fever Virus and Its Immunological Implications,http://dx.doi.org/10.1371/journal.pone.0125692,PMC4418595,25938664,CC BY,"It is well established that trans-placental transmission of classical swine fever virus (CSFV) during mid-gestation can lead to persistently infected offspring. The aim of the present study was to evaluate the ability of CSFV to induce viral persistence upon early postnatal infection. Two litters of 10 piglets each were infected intranasally on the day of birth with low and moderate virulence CSFV isolates, respectively. During six weeks after postnatal infection, most of the piglets remained clinically healthy, despite persistent high virus titres in the serum. Importantly, these animals were unable to mount any detectable humoral and cellular immune response. At necropsy, the most prominent gross pathological lesion was a severe thymus atrophy. Four weeks after infection, PBMCs from the persistently infected seronegative piglets were unresponsive to both, specific CSFV and non-specific PHA stimulation in terms of IFN-γ-producing cells. These results suggested the development of a state of immunosuppression in these postnatally persistently infected pigs. However, IL-10 was undetectable in the sera of the persistently infected animals. Interestingly, CSFV-stimulated PBMCs from the persistently infected piglets produced IL-10. Nevertheless, despite the addition of the anti-IL-10 antibody in the PBMC culture from persistently infected piglets, the response of the IFN-γ producing cells was not restored. Therefore, other factors than IL-10 may be involved in the general suppression of the T-cell responses upon CSFV and mitogen activation. Interestingly, bone marrow immature granulocytes were increased and targeted by the virus in persistently infected piglets. Taken together, we provided the first data demonstrating the feasibility of CSFV in generating a postnatal persistent disease, which has not been shown for other members of the Pestivirus genus yet. Since serological methods are routinely used in CSFV surveillance, persistently infected pigs might go unnoticed. In addition to the epidemiological and economic significance of persistent CSFV infection, this model could be useful for understanding the mechanisms of viral persistence.",2015 May 4,"['Muñoz-González, Sara', 'Ruggli, Nicolas', 'Rosell, Rosa', 'Pérez, Lester Josué', 'Frías-Leuporeau, Maria Teresa', 'Fraile, Lorenzo', 'Montoya, Maria', 'Cordoba, Lorena', 'Domingo, Mariano', 'Ehrensperger, Felix', 'Summerfield, Artur', 'Ganges, Llilianne']",PLoS One,,,True
9c930b820306b68f83b4706c10aae46bf2ed70b7,PMC,Evaluation of porcine epidemic diarrhea virus transmission and the immune response in growing pigs,http://dx.doi.org/10.1186/s13567-015-0180-5,PMC4419466,25943434,CC BY,"Clinical disease associated with porcine epidemic diarrhea virus (PEDV) infection in naïve pigs is well chronicled; however, information on endemic PEDV infection is limited. To characterize chronic PEDV infection, the duration of infectious virus shedding and development of protective immunity was determined. On Day 0 (D0), a growing pig was challenged with PEDV and 13 contacts were commingled. On D7, 9 contact pigs (principal virus group (PG)), were selected, moved to a separate room and commingled with one sentinel pig (S1). This process was repeated weekly with S2, S3 and S4. The PG was PEDV-positive by PCR from D3-11, with some pigs intermittently positive to D42. Pigs S1 and S2 were PEDV-positive within 24 hours of commingling. Antibodies were detected in all PG by D21 and by 7 days post-contact in S1 and S2. Pigs S3 and S4 were PCR and antibody negative following commingling. To evaluate protective immunity, 5 naïve pigs (N) and the PG were challenged (N/C, PG/C) with homologous virus on D49. All N/C pigs were PEDV PCR-positive by D52 with detection out to D62 in 3/5 N/C pigs. All PG/C pigs were PEDV PCR-negative post-challenge. By D63, all N/C seroconverted. Although PEDV RNA was demonstrated in pigs after primary infection until D42, infectious PEDV capable of horizontal transmission to naïve pigs was only shed 14–16 days after infection to age-matched pigs. Homologous re-challenge 49 days post initial PEDV exposure did not result in re-infection of the pigs. This demonstrates potential for an effective PEDV vaccine.",2015 May 6,"['Crawford, Kimberly', 'Lager, Kelly', 'Miller, Laura', 'Opriessnig, Tanja', 'Gerber, Priscilla', 'Hesse, Richard']",Vet Res,,,True
ebac83e8603fe1bfb0091c0733f9a10c95208599,PMC,Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis,http://dx.doi.org/10.1186/s12879-015-0938-4,PMC4419503,25928122,CC BY,"BACKGROUND: Sepsis is a serious medical condition requiring timely administered, appropriate antibiotic therapy. Blood culture is regarded as the gold standard for aetiological diagnosis of sepsis, but it suffers from low sensitivity and long turnaround time. Thus, nucleic acid amplification tests (NAATs) have emerged to shorten the time to identification of causative microbes. The aim of the present study was to evaluate the clinical utility in everyday practice in the emergency department of two commercial NAATs in patients suspected with sepsis. METHODS: During a six-week period, blood samples were collected consecutively from all adult patients admitted to the general emergency department for suspicion of a community-onset sepsis and treated with intravenous antibiotics. Along with conventional blood cultures, multiplex PCR (Magicplex™) was performed on whole blood specimens whereas portions from blood culture bottles were used for analysis by microarray-based assay (Prove-it™). The aetiological significance of identified organisms was determined by two infectious disease physicians based on clinical presentation and expected pathogenicity. RESULTS: Among 382 episodes of suspected sepsis, clinically relevant microbes were detected by blood culture in 42 episodes (11%), by multiplex PCR in 37 episodes (9.7%), and by microarray in 32 episodes (8.4%). Although moderate agreement with blood culture (kappa 0.50), the multiplex PCR added diagnostic value by timely detection of 15 clinically relevant findings in blood culture-negative specimens. Results of the microarray corresponded very well to those of blood culture (kappa 0.90), but were available just marginally prior to blood culture results. CONCLUSIONS: The use of NAATs on whole blood specimens in adjunct to current culture-based methods provides a clinical add-on value by allowing for detection of organisms missed by blood culture. However, the aetiological significance of findings detected by NAATs should be interpreted with caution as the high analytical sensitivity may add findings that do not necessarily corroborate with the clinical diagnosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0938-4) contains supplementary material, which is available to authorized users.",2015 Apr 28,"['Ljungström, Lars', 'Enroth, Helena', 'Claesson, Berndt EB', 'Ovemyr, Ida', 'Karlsson, Jesper', 'Fröberg, Berit', 'Brodin, Anna-Karin', 'Pernestig, Anna-Karin', 'Jacobsson, Gunnar', 'Andersson, Rune', 'Karlsson, Diana']",BMC Infect Dis,,,False
c3a82cf68990138f6cbbbfe60b5b80d3f6d2e260,PMC,Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis,http://dx.doi.org/10.1186/s12879-015-0938-4,PMC4419503,25928122,CC BY,"BACKGROUND: Sepsis is a serious medical condition requiring timely administered, appropriate antibiotic therapy. Blood culture is regarded as the gold standard for aetiological diagnosis of sepsis, but it suffers from low sensitivity and long turnaround time. Thus, nucleic acid amplification tests (NAATs) have emerged to shorten the time to identification of causative microbes. The aim of the present study was to evaluate the clinical utility in everyday practice in the emergency department of two commercial NAATs in patients suspected with sepsis. METHODS: During a six-week period, blood samples were collected consecutively from all adult patients admitted to the general emergency department for suspicion of a community-onset sepsis and treated with intravenous antibiotics. Along with conventional blood cultures, multiplex PCR (Magicplex™) was performed on whole blood specimens whereas portions from blood culture bottles were used for analysis by microarray-based assay (Prove-it™). The aetiological significance of identified organisms was determined by two infectious disease physicians based on clinical presentation and expected pathogenicity. RESULTS: Among 382 episodes of suspected sepsis, clinically relevant microbes were detected by blood culture in 42 episodes (11%), by multiplex PCR in 37 episodes (9.7%), and by microarray in 32 episodes (8.4%). Although moderate agreement with blood culture (kappa 0.50), the multiplex PCR added diagnostic value by timely detection of 15 clinically relevant findings in blood culture-negative specimens. Results of the microarray corresponded very well to those of blood culture (kappa 0.90), but were available just marginally prior to blood culture results. CONCLUSIONS: The use of NAATs on whole blood specimens in adjunct to current culture-based methods provides a clinical add-on value by allowing for detection of organisms missed by blood culture. However, the aetiological significance of findings detected by NAATs should be interpreted with caution as the high analytical sensitivity may add findings that do not necessarily corroborate with the clinical diagnosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0938-4) contains supplementary material, which is available to authorized users.",2015 Apr 28,"['Ljungström, Lars', 'Enroth, Helena', 'Claesson, Berndt EB', 'Ovemyr, Ida', 'Karlsson, Jesper', 'Fröberg, Berit', 'Brodin, Anna-Karin', 'Pernestig, Anna-Karin', 'Jacobsson, Gunnar', 'Andersson, Rune', 'Karlsson, Diana']",BMC Infect Dis,,,True
d17a476d549a21be3e70932a10c6fef328f42ba6,PMC,Griffithsin tandemers: flexible and potent lectin inhibitors of the human immunodeficiency virus,http://dx.doi.org/10.1186/s12977-014-0127-3,PMC4419512,25613831,CC BY,"BACKGROUND: The lectin griffithsin (GRFT) is a potent antiviral agent capable of prevention and treatment of infections caused by a number of enveloped viruses and is currently under development as an anti-HIV microbicide. In addition to its broad antiviral activity, GRFT is stable at high temperature and at a broad pH range, displays little toxicity and immunogenicity, and is amenable to large-scale manufacturing. Native GRFT is a domain-swapped homodimer that binds to viral envelope glycoproteins and has displayed mid-picomolar activity in cell-based anti-HIV assays. Previously, we have engineered and analyzed several monomeric forms of this lectin (mGRFT) with anti-HIV EC(50) values ranging up to 323 nM. Based on our previous analysis of mGRFT, we hypothesized that the orientation and spacing of the carbohydrate binding domains GRFT were key to its antiviral activity. RESULTS: Here we present data on engineered tandem repeats of mGRFT (mGRFT tandemers) with antiviral activity at concentrations as low as one picomolar in whole-cell anti-HIV assays. mGRFT tandemers were analyzed thermodynamically, both individually and in complex with HIV-1 gp120. We also demonstrate by dynamic light scattering and cryo-electron microscopy that mGRFT tandemers do not aggregate HIV virions. This establishes that, although the intra-virion crosslinking of HIV envelope glycoproteins is likely integral to their activity, the antiviral activity of these lectins is not due to virus aggregation caused by inter-virion crosslinking. CONCLUSIONS: The engineered tandemer constructs of mGRFT may provide novel and powerful agents for prevention of infection by HIV and other enveloped viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-014-0127-3) contains supplementary material, which is available to authorized users.",2015 Jan 23,"['Moulaei, Tinoush', 'Alexandre, Kabamba B', 'Shenoy, Shilpa R', 'Meyerson, Joel R', 'Krumpe, Lauren RH', 'Constantine, Brian', 'Wilson, Jennifer', 'Buckheit, Robert W', 'McMahon, James B', 'Subramaniam, Sriram', 'Wlodawer, Alexander', 'O’Keefe, Barry R']",Retrovirology,,,True
34f0507e2d36312bb0a90c6c9a66acd14d9154c3,PMC,OASes and STING: Adaptive Evolution in Concert,http://dx.doi.org/10.1093/gbe/evv046,PMC4419793,25752600,CC BY,"OAS (2′–5′-oligoadenylate synthases) proteins and cyclic GMP–AMP synthase (cGAS, gene symbol: MB21D1) patrol the cytoplasm for the presence of foreign nucleic acids. Upon binding to double-stranded RNA or double-stranded DNA, OAS proteins and cGAS produce nucleotide second messengers to activate RNase L and STING (stimulator of interferon genes, gene symbol: TMEM173), respectively; this leads to the initiation of antiviral responses. We analyzed the evolutionary history of the MB21D1–TMEM173 and OAS–RNASEL axes in primates and bats and found evidence of widespread positive selection in both orders. In TMEM173, residue 230, a major determinant of response to natural ligands and to mimetic drugs (e.g., DMXAA), was positively selected in Primates and Chiroptera. In both orders, selection also targeted an α-helix/loop element in RNase L that modulates the enzyme preference for single-stranded RNA versus stem loops. Analysis of positively selected sites in OAS1, OAS2, and MB21D1 revealed parallel evolution, with the corresponding residues being selected in different genes. As this cannot result from gene conversion, these data suggest that selective pressure acting on OAS and MB21D1 genes is related to nucleic acid recognition and to the specific mechanism of enzyme activation, which requires a conformational change. Finally, a population genetics-phylogenetics analysis in humans, chimpanzees, and gorillas detected several positively selected sites in most genes. Data herein shed light into species-specific differences in infection susceptibility and in response to synthetic compounds, with relevance for the design of synthetic compounds as vaccine adjuvants.",2015 Mar 9,"['Mozzi, Alessandra', 'Pontremoli, Chiara', 'Forni, Diego', 'Clerici, Mario', 'Pozzoli, Uberto', 'Bresolin, Nereo', 'Cagliani, Rachele', 'Sironi, Manuela']",Genome Biol Evol,,,True
526b8ff2051f296de62ce8ceccc0d384c2e68c6a,PMC,OASes and STING: Adaptive Evolution in Concert,http://dx.doi.org/10.1093/gbe/evv046,PMC4419793,25752600,CC BY,"OAS (2′–5′-oligoadenylate synthases) proteins and cyclic GMP–AMP synthase (cGAS, gene symbol: MB21D1) patrol the cytoplasm for the presence of foreign nucleic acids. Upon binding to double-stranded RNA or double-stranded DNA, OAS proteins and cGAS produce nucleotide second messengers to activate RNase L and STING (stimulator of interferon genes, gene symbol: TMEM173), respectively; this leads to the initiation of antiviral responses. We analyzed the evolutionary history of the MB21D1–TMEM173 and OAS–RNASEL axes in primates and bats and found evidence of widespread positive selection in both orders. In TMEM173, residue 230, a major determinant of response to natural ligands and to mimetic drugs (e.g., DMXAA), was positively selected in Primates and Chiroptera. In both orders, selection also targeted an α-helix/loop element in RNase L that modulates the enzyme preference for single-stranded RNA versus stem loops. Analysis of positively selected sites in OAS1, OAS2, and MB21D1 revealed parallel evolution, with the corresponding residues being selected in different genes. As this cannot result from gene conversion, these data suggest that selective pressure acting on OAS and MB21D1 genes is related to nucleic acid recognition and to the specific mechanism of enzyme activation, which requires a conformational change. Finally, a population genetics-phylogenetics analysis in humans, chimpanzees, and gorillas detected several positively selected sites in most genes. Data herein shed light into species-specific differences in infection susceptibility and in response to synthetic compounds, with relevance for the design of synthetic compounds as vaccine adjuvants.",2015 Mar 9,"['Mozzi, Alessandra', 'Pontremoli, Chiara', 'Forni, Diego', 'Clerici, Mario', 'Pozzoli, Uberto', 'Bresolin, Nereo', 'Cagliani, Rachele', 'Sironi, Manuela']",Genome Biol Evol,,,False
eb0d926b1fa6dc7d9f86a001f8ccd69407c5ed86,PMC,Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1 Suggest a Common Mechanism of Pathogen Antagonism and Escape,http://dx.doi.org/10.1371/journal.pgen.1005203,PMC4420275,25942676,CC BY,"A diverse subset of pattern recognition receptors (PRRs) detects pathogen-associated nucleic acids to initiate crucial innate immune responses in host organisms. Reflecting their importance for host defense, pathogens encode various countermeasures to evade or inhibit these immune effectors. PRRs directly engaged by pathogen inhibitors often evolve under recurrent bouts of positive selection that have been described as molecular ‘arms races.’ Cyclic GMP-AMP synthase (cGAS) was recently identified as a key PRR. Upon binding cytoplasmic double-stranded DNA (dsDNA) from various viruses, cGAS generates the small nucleotide secondary messenger cGAMP to signal activation of innate defenses. Here we report an evolutionary history of cGAS with recurrent positive selection in the primate lineage. Recent studies indicate a high degree of structural similarity between cGAS and 2’-5’-oligoadenylate synthase 1 (OAS1), a PRR that detects double-stranded RNA (dsRNA), despite low sequence identity between the respective genes. We present comprehensive comparative evolutionary analysis of cGAS and OAS1 primate sequences and observe positive selection at nucleic acid binding interfaces and distributed throughout both genes. Our data revealed homologous regions with strong signatures of positive selection, suggesting common mechanisms employed by unknown pathogen encoded inhibitors and similar modes of evasion from antagonism. Our analysis of cGAS diversification also identified alternately spliced forms missing multiple sites under positive selection. Further analysis of selection on the OAS family in primates, which comprises OAS1, OAS2, OAS3 and OASL, suggests a hypothesis where gene duplications and domain fusion events result in paralogs that provide another means of escaping pathogen inhibitors. Together our comparative evolutionary analysis of cGAS and OAS provides new insights into distinct mechanisms by which key molecular sentinels of the innate immune system have adapted to circumvent viral-encoded inhibitors.",2015 May 5,"['Hancks, Dustin C.', 'Hartley, Melissa K.', 'Hagan, Celia', 'Clark, Nathan L.', 'Elde, Nels C.']",PLoS Genet,,,True
396312dfae0562afce275a99e96c903e91aa96c9,PMC,Interferon-Inducible Transmembrane Protein 3 Genetic Variant rs12252 and Influenza Susceptibility and Severity: A Meta-Analysis,http://dx.doi.org/10.1371/journal.pone.0124985,PMC4420464,25942469,CC BY,"BACKGROUND: The pandemic influenza A (H1N1) pdm09 virus, avian influenza A (H5N1) virus, and influenza A (H7N9) virus induced severe morbidity and mortality throughout the world. Previous studies suggested a close association between the interferon-induced transmembrane protein-3 (IFITM3) genetic variant rs12252 and influenza. Here, we explored the correlation between the rs12252 and influenza susceptibility and severity using meta-analysis. METHODS: Relevant studies published before May 22, 2014 were retrieved from PubMed, ISI web of knowledge, EBSCO, and Cochrane central register of controlled trials databases. Association between rs12252 and influenza susceptibility and severity were determined using statistical analysis of odds ratios (ORs). RESULTS: A total of four studies consisting of 445 cases and 4180 controls were included in our analysis. Generally, there is increased risk of influenza in subjects carrying rs12252 in the recessive model (CC vs. CT+TT: OR = 2.35, 95% CI: 1.49-3.70, P<0.001), the dominant model (CC+CT vs. TT: OR=1.60, 95% CI: 1.18–2.22, P=0.003), the homozygote comparison (CC vs. TT: OR=4.11, 95% CI: 2.15–7.84, P<0.001), and the allele contrast (C vs. T: OR=1.67, 95% CI: 1.32–2.13, P<0.001). Stratification analysis of ethnicity and severity revealed a significant increase in influenza susceptibility by IFITM3-SNP rs12252 among both Asian and Caucasian population. SNP rs12252 shows significant impact on severe infections (P<0.05), but not on mild influenza. Besides, our result also associated rs12252 with influenza severity (severe vs. mild: OR=2.37, 95% CI: 1.32–4.25, P=0.004), (severe vs. control: OR=2.70, 95% CI: 1.85–3.94, P<0.001). CONCLUSION: Our meta-analysis suggests a significant association between a minor IFITM3 allele (SNP rs12252-C) with severe influenza susceptibility, but not in mild influenza subjects, in both UK Caucasians and Han Chinese population. The rs12252-C allele causes a 23.7% higher chance of infection and also constitutes a risk factor for more severe influenza.",2015 May 5,"['Yang, Xianxian', 'Tan, Bin', 'Zhou, Xipeng', 'Xue, Jian', 'Zhang, Xian', 'Wang, Peng', 'Shao, Chuang', 'Li, Yingli', 'Li, Chaorui', 'Xia, Huiming', 'Qiu, Jingfu']",PLoS One,,,True
6bfa66e7befc8ca735ef61dc392a32d1c56ea01e,PMC,Perturbations at the ribosomal genes loci are at the centre of cellular dysfunction and human disease,http://dx.doi.org/10.1186/2045-3701-4-43,PMC4422213,25949792,CC BY,"Ribosomal RNA (rRNA) gene (rDNA) transcription by RNA Polymerase I (Pol I) drives cell growth and underlies nucleolar structure and function, indirectly coordinating many fundamental cellular processes. The importance of keeping rDNA transcription under tight control is reflected by the fact that deranged Pol I transcription is a feature of cancer and other human disorders. In this review, we discuss multiple aspects of rDNA function including the relationship between Pol I transcription and proliferative capacity, the role of Pol I transcription in mediating nucleolar structure and integrity, and rDNA/nucleolar interactions with the genome and their influence on heterochromatin and global genome stability. Furthermore, we discuss how perturbations in the structure of the rDNA loci might contribute to human disease, in some cases independent of effects on ribosome biogenesis.",2014 Aug 19,"['Diesch, Jeannine', 'Hannan, Ross D', 'Sanij, Elaine']",Cell Biosci,,,True
215fb42f8f5f2ede1ed7e7b1561e51f494593578,PMC,Modulation of angiotensin II signaling in the prevention of fibrosis,http://dx.doi.org/10.1186/s13069-015-0023-z,PMC4422447,25949522,CC BY,"Over the last decade, it has become clear that the role of angiotensin II extends far beyond recognized renal and cardiovascular effects. The presence of an autologous renin-angiotensin system has been demonstrated in almost all tissues of the body. It is now known that angiotensin II acts both independently and in synergy with TGF-beta to induce fibrosis via the angiotensin type 1 receptor (AT(1)) in a multitude of tissues outside of the cardiovascular and renal systems, including pulmonary fibrosis, intra-abdominal fibrosis, and systemic sclerosis. Interestingly, recent studies have described a paradoxically regenerative effect of the angiotensin system via stimulation of the angiotensin type 2 receptor (AT(2)). Activation of AT(2) has been shown to ameliorate fibrosis in animal models of skeletal muscle, gastrointestinal, and neurologic diseases. Clinical reports suggest a beneficial role for modulation of angiotensin II signaling in cutaneous scarring. This article reviews current knowledge on the role that angiotensin II plays in tissue fibrosis, as well as current and potential therapies targeting this system.",2015 Apr 23,"['Murphy, Amanda M', 'Wong, Alison L', 'Bezuhly, Michael']",Fibrogenesis Tissue Repair,,,True
c2986eb912dbecc9c8508361012392706955076e,PMC,Viroporin Activity of the Foot-and-Mouth Disease Virus Non-Structural 2B Protein,http://dx.doi.org/10.1371/journal.pone.0125828,PMC4422707,25946195,CC BY,"Viroporins are a family of low-molecular-weight hydrophobic transmembrane proteins that are encoded by various animal viruses. Viroporins form transmembrane pores in host cells via oligomerization, thereby destroying cellular homeostasis and inducing cytopathy for virus replication and virion release. Among the Picornaviridae family of viruses, the 2B protein encoded by enteroviruses is well understood, whereas the viroporin activity of the 2B protein encoded by the foot-and-mouth disease virus (FMDV) has not yet been described. An analysis of the FMDV 2B protein domains by computer-aided programs conducted in this study revealed that this protein may contain two transmembrane regions. Further biochemical, biophysical and functional studies revealed that the protein possesses a number of features typical of a viroporin when it is overexpressed in bacterial and mammalian cells as well as in FMDV-infected cells. The protein was found to be mainly localized in the endoplasmic reticulum (ER), with both the N- and C-terminal domains stretched into the cytosol. It exhibited cytotoxicity in Escherichia coli, which attenuated 2B protein expression. The release of virions from cells infected with FMDV was inhibited by amantadine, a viroporin inhibitor. The 2B protein monomers interacted with each other to form both intracellular and extracellular oligomers. The Ca(2+) concentration in the cells increased, and the integrity of the cytoplasmic membrane was disrupted in cells that expressed the 2B protein. Moreover, the 2B protein induced intense autophagy in host cells. All of the results of this study demonstrate that the FMDV 2B protein has properties that are also found in other viroporins and may be involved in the infection mechanism of FMDV.",2015 May 6,"['Ao, Da', 'Guo, Hui-Chen', 'Sun, Shi-Qi', 'Sun, De-Hui', 'Fung, To Sing', 'Wei, Yan-Quan', 'Han, Shi-Chong', 'Yao, Xue-Ping', 'Cao, Sui-Zhong', 'Liu, Ding Xiang', 'Liu, Xiang-Tao']",PLoS One,,,True
d4718ccc1c08a82371c1d7525aae8cc567ff2424,PMC,Chinese Social Media Reaction to Information about 42 Notifiable Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0126092,PMC4422708,25946020,CC BY,This study aimed to identify what information triggered social media users’ responses regarding infectious diseases. Chinese microblogs in 2012 regarding 42 infectious diseases were obtained through a keyword search in the Weiboscope database. Qualitative content analysis was performed for the posts pertinent to each keyword of the day of the year with the highest daily count. Similar posts were grouped and coded. We identified five categories of information that increased microblog traffic pertaining to infectious diseases: news of an outbreak or a case; health education / information; alternative health information / Traditional Chinese Medicine; commercial advertisement / entertainment; and social issues. News unrelated to the specified infectious diseases also led to elevated microblog traffic. Our study showcases the diverse contexts from which increased social media traffic occur. Our results will facilitate better health communication as causes underlying increased social media traffic are revealed.,2015 May 6,"['Fung, Isaac Chun-Hai', 'Hao, Yi', 'Cai, Jingxian', 'Ying, Yuchen', 'Schaible, Braydon James', 'Yu, Cynthia Mengxi', 'Tse, Zion Tsz Ho', 'Fu, King-Wa']",PLoS One,,,True
f7d4270a51caf2ea8758476bad0e0537f2d47075,PMC,Chinese Social Media Reaction to Information about 42 Notifiable Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0126092,PMC4422708,25946020,CC BY,This study aimed to identify what information triggered social media users’ responses regarding infectious diseases. Chinese microblogs in 2012 regarding 42 infectious diseases were obtained through a keyword search in the Weiboscope database. Qualitative content analysis was performed for the posts pertinent to each keyword of the day of the year with the highest daily count. Similar posts were grouped and coded. We identified five categories of information that increased microblog traffic pertaining to infectious diseases: news of an outbreak or a case; health education / information; alternative health information / Traditional Chinese Medicine; commercial advertisement / entertainment; and social issues. News unrelated to the specified infectious diseases also led to elevated microblog traffic. Our study showcases the diverse contexts from which increased social media traffic occur. Our results will facilitate better health communication as causes underlying increased social media traffic are revealed.,2015 May 6,"['Fung, Isaac Chun-Hai', 'Hao, Yi', 'Cai, Jingxian', 'Ying, Yuchen', 'Schaible, Braydon James', 'Yu, Cynthia Mengxi', 'Tse, Zion Tsz Ho', 'Fu, King-Wa']",PLoS One,,,True
471d79fab1a95464be76c77dce4a2e263ca8b443,PMC,Evaluation of a Phylogenetic Marker Based on Genomic Segment B of Infectious Bursal Disease Virus: Facilitating a Feasible Incorporation of this Segment to the Molecular Epidemiology Studies for this Viral Agent,http://dx.doi.org/10.1371/journal.pone.0125853,PMC4422720,25946336,CC BY,"BACKGROUND: Infectious bursal disease (IBD) is a highly contagious and acute viral disease, which has caused high mortality rates in birds and considerable economic losses in different parts of the world for more than two decades and it still represents a considerable threat to poultry. The current study was designed to rigorously measure the reliability of a phylogenetic marker included into segment B. This marker can facilitate molecular epidemiology studies, incorporating this segment of the viral genome, to better explain the links between emergence, spreading and maintenance of the very virulent IBD virus (vvIBDV) strains worldwide. METHODOLOGY/PRINCIPAL FINDINGS: Sequences of the segment B gene from IBDV strains isolated from diverse geographic locations were obtained from the GenBank Database; Cuban sequences were obtained in the current work. A phylogenetic marker named B-marker was assessed by different phylogenetic principles such as saturation of substitution, phylogenetic noise and high consistency. This last parameter is based on the ability of B-marker to reconstruct the same topology as the complete segment B of the viral genome. From the results obtained from B-marker, demographic history for both main lineages of IBDV regarding segment B was performed by Bayesian skyline plot analysis. Phylogenetic analysis for both segments of IBDV genome was also performed, revealing the presence of a natural reassortant strain with segment A from vvIBDV strains and segment B from non-vvIBDV strains within Cuban IBDV population. CONCLUSIONS/SIGNIFICANCE: This study contributes to a better understanding of the emergence of vvIBDV strains, describing molecular epidemiology of IBDV using the state-of-the-art methodology concerning phylogenetic reconstruction. This study also revealed the presence of a novel natural reassorted strain as possible manifest of change in the genetic structure and stability of the vvIBDV strains. Therefore, it highlights the need to obtain information about both genome segments of IBDV for molecular epidemiology studies.",2015 May 6,"['Alfonso-Morales, Abdulahi', 'Rios, Liliam', 'Martínez-Pérez, Orlando', 'Dolz, Roser', 'Valle, Rosa', 'Perera, Carmen L.', 'Bertran, Kateri', 'Frías, Maria T.', 'Ganges, Llilianne', 'Díaz de Arce, Heidy', 'Majó, Natàlia', 'Núñez, José I.', 'Pérez, Lester J.']",PLoS One,,,True
78a0953f03d4dd00f2b4234e3768d95a700202dc,PMC,Mixed Viral Infections Circulating in Hospitalized Patients with Respiratory Tract Infections in Kuwait,http://dx.doi.org/10.1155/2015/714062,PMC4423027,25983755,CC BY,"The aim of this study was to determine the frequency of viral mixed detection in hospitalized patients with respiratory tract infections and to evaluate the correlation between viral mixed detection and clinical severity. Hospitalized patients with respiratory tract infections (RTI) were investigated for 15 respiratory viruses by using sensitive molecular techniques. In total, 850 hospitalized patients aged between 3 days and 80 years were screened from September 2010 to April 2014. Among the 351 (47.8%) patients diagnosed with viral infections, viral mixed detection was identified in 49 patients (14%), with human rhinovirus (HRV) being the most common virus associated with viral mixed detection (7.1%), followed by adenovirus (AdV) (4%) and human coronavirus-OC43 (HCoV-OC43) (3.7%). The highest combination of viral mixed detection was identified with HRV and AdV (2%), followed by HRV and HCoV-OC43 (1.4%). Pneumonia and bronchiolitis were the most frequent reason for hospitalization with viral mixed detection (9.1%). There were statistical significance differences between mixed and single detection in patients diagnosed with bronchiolitis (P = 0.002) and pneumonia (P = 0.019). Our findings might indicate a significant association between respiratory virus mixed detection and the possibility of developing more severe LRTI such as bronchiolitis and pneumonia when compared with single detection.",2015 Apr 23,"['Essa, Sahar', 'Owayed, Abdullah', 'Altawalah, Haya', 'Khadadah, Mousa', 'Behbehani, Nasser', 'Al-Nakib, Widad']",Adv Virol,,,True
1b02698e082376846f59c99c449161a7a7eb737f,PMC,Drak2 Does Not Regulate TGF-β Signaling in T Cells,http://dx.doi.org/10.1371/journal.pone.0123650,PMC4423867,25951457,CC BY,"Drak2 is a serine/threonine kinase expressed highest in T cells and B cells. Drak2(-/-) mice are resistant to autoimmunity in mouse models of type 1 diabetes and multiple sclerosis. Resistance to these diseases occurs, in part, because Drak2 is required for the survival of autoreactive T cells that induce disease. However, the molecular mechanisms by which Drak2 affects T cell survival and autoimmunity are not known. A recent report demonstrated that Drak2 negatively regulated transforming growth factor-β (TGF-β) signaling in tumor cell lines. Thus, increased TGF-β signaling in the absence of Drak2 may contribute to the resistance to autoimmunity in Drak2(-/-) mice. Therefore, we examined if Drak2 functioned as a negative regulator of TGF-β signaling in T cells, and whether the enhanced susceptibility to death of Drak2(-/-) T cells was due to augmented TGF-β signaling. Using several in vitro assays to test TGF-β signaling and T cell function, we found that activation of Smad2 and Smad3, which are downstream of the TGF-β receptor, was similar between wildtype and Drak2(-/-) T cells. Furthermore, TGF-β-mediated effects on naïve T cell proliferation, activated CD8(+) T cell survival, and regulatory T cell induction was similar between wildtype and Drak2(-/-) T cells. Finally, the increased susceptibility to death in the absence of Drak2 was not due to enhanced TGF-β signaling. Together, these data suggest that Drak2 does not function as a negative regulator of TGF-β signaling in primary T cells stimulated in vitro. It is important to investigate and discern potential molecular mechanisms by which Drak2 functions in order to better understand the etiology of autoimmune diseases, as well as to validate the use of Drak2 as a target for therapeutic treatment of these diseases.",2015 May 7,"['Harris, Tarsha L.', 'McGargill, Maureen A.']",PLoS One,,,True
78c1291690eec42eb88c56d3c1e878b43409a928,PMC,Full-Genome Sequence of Pantropic Canine Coronavirus,http://dx.doi.org/10.1128/genomeA.00401-15,PMC4424302,25953186,CC BY,"Pantropic canine coronavirus (CCoV) was first detected in young dogs in Italy in 2005, but the complete genome sequence of this virus had not yet been determined. Here, we report the full-length genome sequence of the prototype strain CB/05, which showed that this virus is genetically similar to CCoV-IIa viruses.",2015 May 7,"['Decaro, Nicola', 'Mari, Viviana', 'Dowgier, Giulia', 'Elia, Gabriella', 'Lanave, Gianvito', 'Colaianni, Maria Loredana', 'Buonavoglia, Canio']",Genome Announc,,,True
7bab005205a7ee772e476d7dbcf5eee3aed12826,PMC,"Deletion of Fibrinogen-like Protein 2 (FGL-2), a Novel CD4(+) CD25(+) Treg Effector Molecule, Leads to Improved Control of Echinococcus multilocularis Infection in Mice",http://dx.doi.org/10.1371/journal.pntd.0003755,PMC4425495,25955764,CC BY,"BACKGROUND: The growth potential of the tumor-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly linked to the nature/function of the periparasitic host immune-mediated processes. We previously showed that Fibrinogen-like-protein 2 (FGL2), a novel CD4(+)CD25(+) Treg effector molecule, was over-expressed in the liver of mice experimentally infected with E. multilocularis. However, little is known about its contribution to the control of this chronic helminth infection. METHODS/FINDINGS: Key parameters for infection outcome in E. multilocularis-infected fgl2(-/-) (AE-fgl2(-/-)) and wild type (AE-WT) mice at 1 and 4 month(s) post-infection were (i) parasite load (i. e. wet weight of parasitic metacestode tissue), and (ii) parasite cell proliferation as assessed by determining E. multilocularis 14-3-3 gene expression levels. Serum FGL2 levels were measured by ELISA. Spleen cells cultured with ConA for 48h or with E. multilocularis Vesicle Fluid (VF) for 96h were analyzed ex-vivo and in-vitro. In addition, spleen cells from non-infected WT mice were cultured with rFGL2/anti-FGL2 or rIL-17A/anti-IL-17A for further functional studies. For Treg-immune-suppression-assays, purified CD4(+)CD25(+) Treg suspensions were incubated with CD4(+) effector T cells in the presence of ConA and irradiated spleen cells as APCs. Flow cytometry and qRT-PCR were used to assess Treg, Th17-, Th1-, Th2-type immune responses and maturation of dendritic cells. We showed that AE-fgl2(-/-) mice exhibited (as compared to AE-WT-animals) (a) a significantly lower parasite load with reduced proliferation activity, (b) an increased T cell proliferative response to ConA, (c) reduced Treg numbers and function, and (d) a persistent capacity of Th1 polarization and DC maturation. CONCLUSIONS: FGL2 appears as one of the key players in immune regulatory processes favoring metacestode survival by promoting Treg cell activity and IL-17A production that contributes to FGL2-regulation. Prospectively, targeting FGL2 could be an option to develop an immunotherapy against AE and other chronic parasitic diseases.",2015 May 8,"['Wang, Junhua', 'Vuitton, Dominique A.', 'Müller, Norbert', 'Hemphill, Andrew', 'Spiliotis, Markus', 'Blagosklonov, Oleg', 'Grandgirard, Denis', 'Leib, Stephen L.', 'Shalev, Itay', 'Levy, Gary', 'Lu, Xiaomei', 'Lin, Renyong', 'Wen, Hao', 'Gottstein, Bruno']",PLoS Negl Trop Dis,,,True
166142fd39f6000cf789299a7df7fedc36b300cb,PMC,Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus,http://dx.doi.org/10.1371/journal.ppat.1004897,PMC4425567,25954804,CC BY,"In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able to compensate for MyD88 deficiency in mice. Similar mechanisms likely contribute to protect MyD88- or IRAK4-deficient patients from viral infections.",2015 May 8,"['Cocita, Clément', 'Guiton, Rachel', 'Bessou, Gilles', 'Chasson, Lionel', 'Boyron, Marilyn', 'Crozat, Karine', 'Dalod, Marc']",PLoS Pathog,,,True
9ce43d96d671f1951120336aa5c311cb01c38933,PMC,Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus,http://dx.doi.org/10.1371/journal.ppat.1004897,PMC4425567,25954804,CC BY,"In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able to compensate for MyD88 deficiency in mice. Similar mechanisms likely contribute to protect MyD88- or IRAK4-deficient patients from viral infections.",2015 May 8,"['Cocita, Clément', 'Guiton, Rachel', 'Bessou, Gilles', 'Chasson, Lionel', 'Boyron, Marilyn', 'Crozat, Karine', 'Dalod, Marc']",PLoS Pathog,,,False
9ba0bcbbdf07e2bc0f584257747428a133ce438e,PMC,Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus,http://dx.doi.org/10.1371/journal.ppat.1004897,PMC4425567,25954804,CC BY,"In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able to compensate for MyD88 deficiency in mice. Similar mechanisms likely contribute to protect MyD88- or IRAK4-deficient patients from viral infections.",2015 May 8,"['Cocita, Clément', 'Guiton, Rachel', 'Bessou, Gilles', 'Chasson, Lionel', 'Boyron, Marilyn', 'Crozat, Karine', 'Dalod, Marc']",PLoS Pathog,,,False
9a2c679df3c8fb1c009087327396cb1aae759b42,PMC,Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus,http://dx.doi.org/10.1371/journal.ppat.1004897,PMC4425567,25954804,CC BY,"In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able to compensate for MyD88 deficiency in mice. Similar mechanisms likely contribute to protect MyD88- or IRAK4-deficient patients from viral infections.",2015 May 8,"['Cocita, Clément', 'Guiton, Rachel', 'Bessou, Gilles', 'Chasson, Lionel', 'Boyron, Marilyn', 'Crozat, Karine', 'Dalod, Marc']",PLoS Pathog,,,False
e15919b98993f3fd0f89d3976f4f9b3b64ad0dd5,PMC,Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus,http://dx.doi.org/10.1371/journal.ppat.1004897,PMC4425567,25954804,CC BY,"In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able to compensate for MyD88 deficiency in mice. Similar mechanisms likely contribute to protect MyD88- or IRAK4-deficient patients from viral infections.",2015 May 8,"['Cocita, Clément', 'Guiton, Rachel', 'Bessou, Gilles', 'Chasson, Lionel', 'Boyron, Marilyn', 'Crozat, Karine', 'Dalod, Marc']",PLoS Pathog,,,False
9275dfe56ef509a8204170bcade177f8a9668c44,PMC,Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus,http://dx.doi.org/10.1371/journal.ppat.1004897,PMC4425567,25954804,CC BY,"In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able to compensate for MyD88 deficiency in mice. Similar mechanisms likely contribute to protect MyD88- or IRAK4-deficient patients from viral infections.",2015 May 8,"['Cocita, Clément', 'Guiton, Rachel', 'Bessou, Gilles', 'Chasson, Lionel', 'Boyron, Marilyn', 'Crozat, Karine', 'Dalod, Marc']",PLoS Pathog,,,False
9921a4035d6dac1772ff49f43fd360286278fd28,PMC,Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus,http://dx.doi.org/10.1371/journal.ppat.1004897,PMC4425567,25954804,CC BY,"In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able to compensate for MyD88 deficiency in mice. Similar mechanisms likely contribute to protect MyD88- or IRAK4-deficient patients from viral infections.",2015 May 8,"['Cocita, Clément', 'Guiton, Rachel', 'Bessou, Gilles', 'Chasson, Lionel', 'Boyron, Marilyn', 'Crozat, Karine', 'Dalod, Marc']",PLoS Pathog,,,False
99667e42abcab43a18c22be949ee54fb1822f34e,PMC,Critical care capacity in Canada: results of a national cross-sectional study,http://dx.doi.org/10.1186/s13054-015-0852-6,PMC4426537,25888116,CC BY,"INTRODUCTION: Intensive Care Units (ICUs) provide life-supporting treatment; however, resources are limited, so demand may exceed supply in the event of pandemics, environmental disasters, or in the context of an aging population. We hypothesized that comprehensive national data on ICU resources would permit a better understanding of regional differences in system capacity. METHODS: After the 2009–2010 Influenza A (H1N1) pandemic, the Canadian Critical Care Trials Group surveyed all acute care hospitals in Canada to assess ICU capacity. Using a structured survey tool administered to physicians, respiratory therapists and nurses, we determined the number of ICU beds, ventilators, and the ability to provide specialized support for respiratory failure. RESULTS: We identified 286 hospitals with 3170 ICU beds and 4982 mechanical ventilators for critically ill patients. Twenty-two hospitals had an ICU that routinely cared for children; 15 had dedicated pediatric ICUs. Per 100,000 population, there was substantial variability in provincial capacity, with a mean of 0.9 hospitals with ICUs (provincial range 0.4-2.8), 10 ICU beds capable of providing mechanical ventilation (provincial range 6–19), and 15 invasive mechanical ventilators (provincial range 10–24). There was only moderate correlation between ventilation capacity and population size (coefficient of determination (R(2)) = 0.771). CONCLUSION: ICU resources vary widely across Canadian provinces, and during times of increased demand, may result in geographic differences in the ability to care for critically ill patients. These results highlight the need to evolve inter-jurisdictional resource sharing during periods of substantial increase in demand, and provide background data for the development of appropriate critical care capacity benchmarks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0852-6) contains supplementary material, which is available to authorized users.",2015 Apr 1,"['Fowler, Robert A', 'Abdelmalik, Philip', 'Wood, Gordon', 'Foster, Denise', 'Gibney, Noel', 'Bandrauk, Natalie', 'Turgeon, Alexis F', 'Lamontagne, François', 'Kumar, Anand', 'Zarychanski, Ryan', 'Green, Rob', 'Bagshaw, Sean M', 'Stelfox, Henry T', 'Foster, Ryan', 'Dodek, Peter', 'Shaw, Susan', 'Granton, John', 'Lawless, Bernard', 'Hill, Andrea', 'Rose, Louise', 'Adhikari, Neill K', 'Scales, Damon C', 'Cook, Deborah J', 'Marshall, John C', 'Martin, Claudio', 'Jouvet, Philippe', None]",Crit Care,,,True
0f8ef4ce069bd394d71e350e4c214d8b2e425a84,PMC,Critical care capacity in Canada: results of a national cross-sectional study,http://dx.doi.org/10.1186/s13054-015-0852-6,PMC4426537,25888116,CC BY,"INTRODUCTION: Intensive Care Units (ICUs) provide life-supporting treatment; however, resources are limited, so demand may exceed supply in the event of pandemics, environmental disasters, or in the context of an aging population. We hypothesized that comprehensive national data on ICU resources would permit a better understanding of regional differences in system capacity. METHODS: After the 2009–2010 Influenza A (H1N1) pandemic, the Canadian Critical Care Trials Group surveyed all acute care hospitals in Canada to assess ICU capacity. Using a structured survey tool administered to physicians, respiratory therapists and nurses, we determined the number of ICU beds, ventilators, and the ability to provide specialized support for respiratory failure. RESULTS: We identified 286 hospitals with 3170 ICU beds and 4982 mechanical ventilators for critically ill patients. Twenty-two hospitals had an ICU that routinely cared for children; 15 had dedicated pediatric ICUs. Per 100,000 population, there was substantial variability in provincial capacity, with a mean of 0.9 hospitals with ICUs (provincial range 0.4-2.8), 10 ICU beds capable of providing mechanical ventilation (provincial range 6–19), and 15 invasive mechanical ventilators (provincial range 10–24). There was only moderate correlation between ventilation capacity and population size (coefficient of determination (R(2)) = 0.771). CONCLUSION: ICU resources vary widely across Canadian provinces, and during times of increased demand, may result in geographic differences in the ability to care for critically ill patients. These results highlight the need to evolve inter-jurisdictional resource sharing during periods of substantial increase in demand, and provide background data for the development of appropriate critical care capacity benchmarks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0852-6) contains supplementary material, which is available to authorized users.",2015 Apr 1,"['Fowler, Robert A', 'Abdelmalik, Philip', 'Wood, Gordon', 'Foster, Denise', 'Gibney, Noel', 'Bandrauk, Natalie', 'Turgeon, Alexis F', 'Lamontagne, François', 'Kumar, Anand', 'Zarychanski, Ryan', 'Green, Rob', 'Bagshaw, Sean M', 'Stelfox, Henry T', 'Foster, Ryan', 'Dodek, Peter', 'Shaw, Susan', 'Granton, John', 'Lawless, Bernard', 'Hill, Andrea', 'Rose, Louise', 'Adhikari, Neill K', 'Scales, Damon C', 'Cook, Deborah J', 'Marshall, John C', 'Martin, Claudio', 'Jouvet, Philippe', None]",Crit Care,,,True
489581af56b842073e88412d6d28cf89c2e08d0e,PMC,"Avoidable errors in the modelling of outbreaks of emerging pathogens, with special reference to Ebola",http://dx.doi.org/10.1098/rspb.2015.0347,PMC4426634,25833863,CC BY,"As an emergent infectious disease outbreak unfolds, public health response is reliant on information on key epidemiological quantities, such as transmission potential and serial interval. Increasingly, transmission models fit to incidence data are used to estimate these parameters and guide policy. Some widely used modelling practices lead to potentially large errors in parameter estimates and, consequently, errors in model-based forecasts. Even more worryingly, in such situations, confidence in parameter estimates and forecasts can itself be far overestimated, leading to the potential for large errors that mask their own presence. Fortunately, straightforward and computationally inexpensive alternatives exist that avoid these problems. Here, we first use a simulation study to demonstrate potential pitfalls of the standard practice of fitting deterministic models to cumulative incidence data. Next, we demonstrate an alternative based on stochastic models fit to raw data from an early phase of 2014 West Africa Ebola virus disease outbreak. We show not only that bias is thereby reduced, but that uncertainty in estimates and forecasts is better quantified and that, critically, lack of model fit is more readily diagnosed. We conclude with a short list of principles to guide the modelling response to future infectious disease outbreaks.",2015 May 7,"['King, Aaron A.', 'Domenech de Cellès, Matthieu', 'Magpantay, Felicia M. G.', 'Rohani, Pejman']",Proc Biol Sci,,,True
15a1cb9e790f884e0513e9f0112a909e95a96c67,PMC,"Avoidable errors in the modelling of outbreaks of emerging pathogens, with special reference to Ebola",http://dx.doi.org/10.1098/rspb.2015.0347,PMC4426634,25833863,CC BY,"As an emergent infectious disease outbreak unfolds, public health response is reliant on information on key epidemiological quantities, such as transmission potential and serial interval. Increasingly, transmission models fit to incidence data are used to estimate these parameters and guide policy. Some widely used modelling practices lead to potentially large errors in parameter estimates and, consequently, errors in model-based forecasts. Even more worryingly, in such situations, confidence in parameter estimates and forecasts can itself be far overestimated, leading to the potential for large errors that mask their own presence. Fortunately, straightforward and computationally inexpensive alternatives exist that avoid these problems. Here, we first use a simulation study to demonstrate potential pitfalls of the standard practice of fitting deterministic models to cumulative incidence data. Next, we demonstrate an alternative based on stochastic models fit to raw data from an early phase of 2014 West Africa Ebola virus disease outbreak. We show not only that bias is thereby reduced, but that uncertainty in estimates and forecasts is better quantified and that, critically, lack of model fit is more readily diagnosed. We conclude with a short list of principles to guide the modelling response to future infectious disease outbreaks.",2015 May 7,"['King, Aaron A.', 'Domenech de Cellès, Matthieu', 'Magpantay, Felicia M. G.', 'Rohani, Pejman']",Proc Biol Sci,,,True
fe9776ca32f2901c58c1df81f6d9767803909869,PMC,"West Nile Virus Positive Blood Donation and Subsequent Entomological Investigation, Austria, 2014",http://dx.doi.org/10.1371/journal.pone.0126381,PMC4427133,25961567,CC BY,"The detection of West Nile virus (WNV) nucleic acid in a blood donation from Vienna, Austria, as well as in Culex pipiens pupae and egg rafts, sampled close to the donor’s residence, is reported. Complete genomic sequences of the human- and mosquito-derived viruses were established, genetically compared and phylogenetically analyzed. The viruses were not identical, but closely related to each other and to recent Czech and Italian isolates, indicating co-circulation of related WNV strains within a confined geographic area. The detection of WNV in a blood donation originating from an area with low WNV prevalence in humans (only three serologically diagnosed cases between 2008 and 2014) is surprising and emphasizes the importance of WNV nucleic acid testing of blood donations even in such areas, along with active mosquito surveillance programs.",2015 May 11,"['Kolodziejek, Jolanta', 'Seidel, Bernhard', 'Jungbauer, Christof', 'Dimmel, Katharina', 'Kolodziejek, Michael', 'Rudolf, Ivo', 'Hubálek, Zdenek', 'Allerberger, Franz', 'Nowotny, Norbert']",PLoS One,,,True
07420d39191900a262a4c5afff61e0ef80eac575,PMC,Regulatory Role of Small Nucleolar RNAs in Human Diseases,http://dx.doi.org/10.1155/2015/206849,PMC4427830,26060813,CC BY,"Small nucleolar RNAs (snoRNAs) are appreciable players in gene expression regulation in human cells. The canonical function of box C/D and box H/ACA snoRNAs is posttranscriptional modification of ribosomal RNAs (rRNAs), namely, 2′-O-methylation and pseudouridylation, respectively. A series of independent studies demonstrated that snoRNAs, as well as other noncoding RNAs, serve as the source of various short regulatory RNAs. Some snoRNAs and their fragments can also participate in the regulation of alternative splicing and posttranscriptional modification of mRNA. Alterations in snoRNA expression in human cells can affect numerous vital cellular processes. SnoRNA level in human cells, blood serum, and plasma presents a promising target for diagnostics and treatment of human pathologies. Here we discuss the relation between snoRNAs and oncological, neurodegenerative, and viral diseases and also describe changes in snoRNA level in response to artificial stress and some drugs.",2015 Apr 28,"['Stepanov, Grigory A.', 'Filippova, Julia A.', 'Komissarov, Andrey B.', 'Kuligina, Elena V.', 'Richter, Vladimir A.', 'Semenov, Dmitry V.']",Biomed Res Int,,,True
d4225ab29dd0f4b357b4667e22037e78b8d95391,PMC,Household practices related to disease transmission between animals and humans in rural Cambodia,http://dx.doi.org/10.1186/s12889-015-1811-5,PMC4427931,25952633,CC BY,"BACKGROUND: Zoonotic diseases are disproportionately affecting poor societies in low-income countries and pose a growing threat to public health and global food security. Rural Cambodian households may face an increased likelihood of exposure to zoonotic diseases as people there live in close association with livestock. The objectives of the study was to identify practices known to influence zoonosis transmission in rural Cambodian households and relate the practices to agro-ecological region, socio-economic position, demographics, livestock management and zoonosis awareness. METHODS: The study was conducted in three different agro-ecological regions of Cambodia; 10 villages each in the central lowlands, north-west wetlands and on the south coast, where information was obtained in questionnaires administered to 300 households, and 30 village heads and animal health workers. RESULTS: Descriptive analysis revealed a gender difference in responsibility for livestock and that the main purpose of raising livestock was for sale. Few respondents (6%) perceived a likelihood of disease transmission in their village between livestock, humans and wildlife, despite household practices related to zoonosis transmission being common. More than one-forth of households practised behaviours such as culling sick animals for consumption, eating animals found dead and allowing animals to enter sleeping and food preparation areas. Associations between household practices and possible explanatory factors were analysed with multivariable models using generalised estimation equations to account for clustering of practices within villages. Factors found to influence household practices were agro-ecological region, socio-economic position, number of people in the household, livestock species reared and awareness of zoonoses. CONCLUSIONS: Cambodia has experienced numerous fatal human cases of zoonotic influenza and extensive influenza information campaigns have been run, yet only a few of the households surveyed here reported the threat of zoonosis to be a concern in their village. Zoonosis awareness was positively related to hand washing behaviour, but other practices associated with an increased or decreased likelihood of exposure to zoonotic pathogens were unaffected by awareness. The findings indicate a knowledge-to-action gap among rural farmers and highlight the necessity for reconstructed interventions in zoonotic disease control. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-1811-5) contains supplementary material, which is available to authorized users.",2015 May 9,"['Osbjer, Kristina', 'Boqvist, Sofia', 'Sokerya, Seng', 'Kannarath, Chheng', 'San, Sorn', 'Davun, Holl', 'Magnusson, Ulf']",BMC Public Health,,,False
76813504d1a92988df75461d6994e860c5cb9ba1,PMC,Household practices related to disease transmission between animals and humans in rural Cambodia,http://dx.doi.org/10.1186/s12889-015-1811-5,PMC4427931,25952633,CC BY,"BACKGROUND: Zoonotic diseases are disproportionately affecting poor societies in low-income countries and pose a growing threat to public health and global food security. Rural Cambodian households may face an increased likelihood of exposure to zoonotic diseases as people there live in close association with livestock. The objectives of the study was to identify practices known to influence zoonosis transmission in rural Cambodian households and relate the practices to agro-ecological region, socio-economic position, demographics, livestock management and zoonosis awareness. METHODS: The study was conducted in three different agro-ecological regions of Cambodia; 10 villages each in the central lowlands, north-west wetlands and on the south coast, where information was obtained in questionnaires administered to 300 households, and 30 village heads and animal health workers. RESULTS: Descriptive analysis revealed a gender difference in responsibility for livestock and that the main purpose of raising livestock was for sale. Few respondents (6%) perceived a likelihood of disease transmission in their village between livestock, humans and wildlife, despite household practices related to zoonosis transmission being common. More than one-forth of households practised behaviours such as culling sick animals for consumption, eating animals found dead and allowing animals to enter sleeping and food preparation areas. Associations between household practices and possible explanatory factors were analysed with multivariable models using generalised estimation equations to account for clustering of practices within villages. Factors found to influence household practices were agro-ecological region, socio-economic position, number of people in the household, livestock species reared and awareness of zoonoses. CONCLUSIONS: Cambodia has experienced numerous fatal human cases of zoonotic influenza and extensive influenza information campaigns have been run, yet only a few of the households surveyed here reported the threat of zoonosis to be a concern in their village. Zoonosis awareness was positively related to hand washing behaviour, but other practices associated with an increased or decreased likelihood of exposure to zoonotic pathogens were unaffected by awareness. The findings indicate a knowledge-to-action gap among rural farmers and highlight the necessity for reconstructed interventions in zoonotic disease control. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-1811-5) contains supplementary material, which is available to authorized users.",2015 May 9,"['Osbjer, Kristina', 'Boqvist, Sofia', 'Sokerya, Seng', 'Kannarath, Chheng', 'San, Sorn', 'Davun, Holl', 'Magnusson, Ulf']",BMC Public Health,,,False
724974cf3a9e24f32408a976803e16254a9803c1,PMC,Household practices related to disease transmission between animals and humans in rural Cambodia,http://dx.doi.org/10.1186/s12889-015-1811-5,PMC4427931,25952633,CC BY,"BACKGROUND: Zoonotic diseases are disproportionately affecting poor societies in low-income countries and pose a growing threat to public health and global food security. Rural Cambodian households may face an increased likelihood of exposure to zoonotic diseases as people there live in close association with livestock. The objectives of the study was to identify practices known to influence zoonosis transmission in rural Cambodian households and relate the practices to agro-ecological region, socio-economic position, demographics, livestock management and zoonosis awareness. METHODS: The study was conducted in three different agro-ecological regions of Cambodia; 10 villages each in the central lowlands, north-west wetlands and on the south coast, where information was obtained in questionnaires administered to 300 households, and 30 village heads and animal health workers. RESULTS: Descriptive analysis revealed a gender difference in responsibility for livestock and that the main purpose of raising livestock was for sale. Few respondents (6%) perceived a likelihood of disease transmission in their village between livestock, humans and wildlife, despite household practices related to zoonosis transmission being common. More than one-forth of households practised behaviours such as culling sick animals for consumption, eating animals found dead and allowing animals to enter sleeping and food preparation areas. Associations between household practices and possible explanatory factors were analysed with multivariable models using generalised estimation equations to account for clustering of practices within villages. Factors found to influence household practices were agro-ecological region, socio-economic position, number of people in the household, livestock species reared and awareness of zoonoses. CONCLUSIONS: Cambodia has experienced numerous fatal human cases of zoonotic influenza and extensive influenza information campaigns have been run, yet only a few of the households surveyed here reported the threat of zoonosis to be a concern in their village. Zoonosis awareness was positively related to hand washing behaviour, but other practices associated with an increased or decreased likelihood of exposure to zoonotic pathogens were unaffected by awareness. The findings indicate a knowledge-to-action gap among rural farmers and highlight the necessity for reconstructed interventions in zoonotic disease control. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-1811-5) contains supplementary material, which is available to authorized users.",2015 May 9,"['Osbjer, Kristina', 'Boqvist, Sofia', 'Sokerya, Seng', 'Kannarath, Chheng', 'San, Sorn', 'Davun, Holl', 'Magnusson, Ulf']",BMC Public Health,,,True
be86d94be6483de622f67e0c098684e4982c0441,PMC,Ethics-sensitivity of the Ghana national integrated strategic response plan for pandemic influenza,http://dx.doi.org/10.1186/s12910-015-0025-9,PMC4427965,25947354,CC BY,"BACKGROUND: Many commentators call for a more ethical approach to planning for influenza pandemics. In the developed world, some pandemic preparedness plans have already been examined from an ethical viewpoint. This paper assesses the attention given to ethics issues by the Ghana National Integrated Strategic Plan for Pandemic Influenza (NISPPI). METHODS: We critically analyzed the Ghana NISPPI’s sensitivity to ethics issues to determine how well it reflects ethical commitments and principles identified in our review of global pandemic preparedness literature, existing pandemic plans, and relevant ethics frameworks. RESULTS: This paper reveals that important ethical issues have not been addressed in the Ghana NISPPI. Several important ethical issues are unanticipated, unacknowledged, and unplanned for. These include guidelines on allocation of scarce resources, the duties of healthcare workers, ethics-sensitive operational guidelines/protocols, and compensation programs. The NISPPI also pays scant attention to use of vaccines and antivirals, border issues and cooperation with neighboring countries, justification for delineated actions, and outbreak simulations. Feedback and communication plans are nebulous, while leadership, coordination, and budgeting are quite detailed. With respect to presentation, the NISPPI’s text is organized around five thematic areas. While each area implicates ethical issues, NISPPI treatment of these areas consistently fails to address them. CONCLUSIONS: Our analysis reveals a lack of consideration of ethics by the NISPPI. We contend that, while the plan’s content and fundamental assumptions provide support for implementation of the delineated public health actions, its consideration of ethical issues is poor. Deficiencies include a failure to incorporate guidelines that ensure fair distribution of scarce resources and a lack of justification for delineated procedures. Until these deficiencies are recognized and addressed, Ghana runs the risk of rolling out unjust and ethically indefensible actions with real negative effects in the event of a pandemic. Soliciting inputs from the public and consultation with ethicists during the next revision of the NISPPI will be useful in addressing these issues.",2015 May 7,"['Laar, Amos', 'DeBruin, Debra']",BMC Med Ethics,,,True
fc89cc67ce1d4e381a17de2c92a9b882f264197d,PMC,Serological Evidence of Influenza A Viruses in Frugivorous Bats from Africa,http://dx.doi.org/10.1371/journal.pone.0127035,PMC4429104,25965069,CC BY,"Bats are likely natural hosts for a range of zoonotic viruses such as Marburg, Ebola, Rabies, as well as for various Corona- and Paramyxoviruses. In 2009/10, researchers discovered RNA of two novel influenza virus subtypes – H17N10 and H18N11 – in Central and South American fruit bats. The identification of bats as possible additional reservoir for influenza A viruses raises questions about the role of this mammalian taxon in influenza A virus ecology and possible public health relevance. As molecular testing can be limited by a short time window in which the virus is present, serological testing provides information about past infections and virus spread in populations after the virus has been cleared. This study aimed at screening available sera from 100 free-ranging, frugivorous bats (Eidolon helvum) sampled in 2009/10 in Ghana, for the presence of antibodies against the complete panel of influenza A haemagglutinin (HA) types ranging from H1 to H18 by means of a protein microarray platform. This technique enables simultaneous serological testing against multiple recombinant HA-types in 5μl of serum. Preliminary results indicate serological evidence against avian influenza subtype H9 in about 30% of the animals screened, with low-level cross-reactivity to phylogenetically closely related subtypes H8 and H12. To our knowledge, this is the first report of serological evidence of influenza A viruses other than H17 and H18 in bats. As avian influenza subtype H9 is associated with human infections, the implications of our findings from a public health context remain to be investigated.",2015 May 12,"['Freidl, Gudrun Stephanie', 'Binger, Tabea', 'Müller, Marcel Alexander', 'de Bruin, Erwin', 'van Beek, Janko', 'Corman, Victor Max', 'Rasche, Andrea', 'Drexler, Jan Felix', 'Sylverken, Augustina', 'Oppong, Samuel K.', 'Adu-Sarkodie, Yaw', 'Tschapka, Marco', 'Cottontail, Veronika M.', 'Drosten, Christian', 'Koopmans, Marion']",PLoS One,,,True
c9c9e146899b877f56ceb3a671fa104787bdf736,PMC,"Ecohealth research in Southeast Asia: past, present and the way forward",http://dx.doi.org/10.1186/2049-9957-4-5,PMC4429815,25973200,CC BY,"Ecohealth is a comprehensive approach to understanding health at its human, animal and environmental interface in a socio-ecological systems context. This approach was introduced widely in Southeast Asia (SEA) by the Canadian International Development Research Centre (IDRC) in the late 2000s. Aimed at addressing the problem of emerging infectious diseases (EIDs), numerous such projects and activities have been generated throughout the region. Ecohealth is increasingly converging with the One Health approach, as both movements emphasise a holistic understanding to health. We conducted a scoping review by considering all of the Ecohealth programmes, initiatives and projects that have been implemented in SEA since the introduction of the approach, and also gathered information from peer-reviewed literature. The objective of this paper is to review Ecohealth activities within SEA over the last 10 years to address the lessons learned, challenges faced and the way forward for Ecohealth in the region. Activities range from those focusing purely on capacity, projects focusing on research and projects covering both. Achievements to date include, for example, research contributing to the field of infectious diseases in relation to social ecological factors and associated urbanisation and agricultural intensification. Challenges remain at the project design and implementation level, in the available capacity and coordination to develop Ecohealth research teams in the countries, gauging teams’ assimilation of Ecohealth’s underlying tenets and their translation into sustainable disease prevention and control, as well as in the ability to scale up Ecohealth projects. We suggest that the way forward for Ecohealth should be from a regional perspective in terms of research, training and policy translation using Ecohealth in combination with the One Health approach. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-4-5) contains supplementary material, which is available to authorized users.",2015 Jan 29,"['Nguyen-Viet, Hung', 'Doria, Siobhan', 'Tung, Dinh Xuan', 'Mallee, Hein', 'Wilcox, Bruce A', 'Grace, Delia']",Infect Dis Poverty,,,False
1495c1fa93db3b9a5d12b5ae15ff0c8639b83452,PMC,"Ecohealth research in Southeast Asia: past, present and the way forward",http://dx.doi.org/10.1186/2049-9957-4-5,PMC4429815,25973200,CC BY,"Ecohealth is a comprehensive approach to understanding health at its human, animal and environmental interface in a socio-ecological systems context. This approach was introduced widely in Southeast Asia (SEA) by the Canadian International Development Research Centre (IDRC) in the late 2000s. Aimed at addressing the problem of emerging infectious diseases (EIDs), numerous such projects and activities have been generated throughout the region. Ecohealth is increasingly converging with the One Health approach, as both movements emphasise a holistic understanding to health. We conducted a scoping review by considering all of the Ecohealth programmes, initiatives and projects that have been implemented in SEA since the introduction of the approach, and also gathered information from peer-reviewed literature. The objective of this paper is to review Ecohealth activities within SEA over the last 10 years to address the lessons learned, challenges faced and the way forward for Ecohealth in the region. Activities range from those focusing purely on capacity, projects focusing on research and projects covering both. Achievements to date include, for example, research contributing to the field of infectious diseases in relation to social ecological factors and associated urbanisation and agricultural intensification. Challenges remain at the project design and implementation level, in the available capacity and coordination to develop Ecohealth research teams in the countries, gauging teams’ assimilation of Ecohealth’s underlying tenets and their translation into sustainable disease prevention and control, as well as in the ability to scale up Ecohealth projects. We suggest that the way forward for Ecohealth should be from a regional perspective in terms of research, training and policy translation using Ecohealth in combination with the One Health approach. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-4-5) contains supplementary material, which is available to authorized users.",2015 Jan 29,"['Nguyen-Viet, Hung', 'Doria, Siobhan', 'Tung, Dinh Xuan', 'Mallee, Hein', 'Wilcox, Bruce A', 'Grace, Delia']",Infect Dis Poverty,,,True
60f1a9fff7e34e6a528a2a06dedb23700c87e114,PMC,Environmental Conditions Affect Exhalation of H3N2 Seasonal and Variant Influenza Viruses and Respiratory Droplet Transmission in Ferrets,http://dx.doi.org/10.1371/journal.pone.0125874,PMC4430532,25969995,CC0,"The seasonality of influenza virus infections in temperate climates and the role of environmental conditions like temperature and humidity in the transmission of influenza virus through the air are not well understood. Using ferrets housed at four different environmental conditions, we evaluated the respiratory droplet transmission of two influenza viruses (a seasonal H3N2 virus and an H3N2 variant virus, the etiologic virus of a swine to human summertime infection) and concurrently characterized the aerosol shedding profiles of infected animals. Comparisons were made among the different temperature and humidity conditions and between the two viruses to determine if the H3N2 variant virus exhibited enhanced capabilities that may have contributed to the infections occurring in the summer. We report here that although increased levels of H3N2 variant virus were found in ferret nasal wash and exhaled aerosol samples compared to the seasonal H3N2 virus, enhanced respiratory droplet transmission was not observed under any of the environmental settings. However, overall environmental conditions were shown to modulate the frequency of influenza virus transmission through the air. Transmission occurred most frequently at 23°C/30%RH, while the levels of infectious virus in aerosols exhaled by infected ferrets agree with these results. Improving our understanding of how environmental conditions affect influenza virus infectivity and transmission may reveal ways to better protect the public against influenza virus infections.",2015 May 13,"['Gustin, Kortney M.', 'Belser, Jessica A.', 'Veguilla, Vic', 'Zeng, Hui', 'Katz, Jacqueline M.', 'Tumpey, Terrence M.', 'Maines, Taronna R.']",PLoS One,,,True
10093bdac52a5e404369bff30a4d38b2bde54276,PMC,Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry,http://dx.doi.org/10.12688/f1000research.6085.2,PMC4431382,26069727,CC BY,"Emerging viral diseases pose a threat to the global population as intervention strategies are mainly limited to basic containment due to the lack of efficacious and approved vaccines and antiviral drugs. The former was the only available intervention when the current unprecedented Ebolavirus (EBOV) outbreak in West Africa began. Prior to this, the development of EBOV vaccines and anti-viral therapies required time and resources that were not available. Therefore, focus has turned to re-purposing of existing, licenced medicines that may limit the morbidity and mortality rates of EBOV and could be used immediately. Here we test three such medicines and measure their ability to inhibit pseudotype viruses (PVs) of two EBOV species, Marburg virus (MARV) and avian influenza H5 (FLU-H5). We confirm the ability of chloroquine (CQ) to inhibit viral entry in a pH specific manner. The commonly used proton pump inhibitors, Omeprazole and Esomeprazole were also able to inhibit entry of all PVs tested but at higher drug concentrations than may be achieved in vivo. We propose CQ as a priority candidate to consider for treatment of EBOV.",2015 Feb 10,"['Long, Jason', 'Wright, Edward', 'Molesti, Eleonora', 'Temperton, Nigel', 'Barclay, Wendy']",F1000Res,,,True
4c4f2d56d08bd5890b44418d237ee5a81afd99fa,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.15.010415,PMC4431563,,CC BY,,2015 Apr 1,,Bull World Health Organ,,,False
eabb427018b4decc5d1e04772814238be2a6d9d6,PMC,Forecasting the 2013–2014 Influenza Season Using Wikipedia,http://dx.doi.org/10.1371/journal.pcbi.1004239,PMC4431683,25974758,CC0,"Infectious diseases are one of the leading causes of morbidity and mortality around the world; thus, forecasting their impact is crucial for planning an effective response strategy. According to the Centers for Disease Control and Prevention (CDC), seasonal influenza affects 5% to 20% of the U.S. population and causes major economic impacts resulting from hospitalization and absenteeism. Understanding influenza dynamics and forecasting its impact is fundamental for developing prevention and mitigation strategies. We combine modern data assimilation methods with Wikipedia access logs and CDC influenza-like illness (ILI) reports to create a weekly forecast for seasonal influenza. The methods are applied to the 2013-2014 influenza season but are sufficiently general to forecast any disease outbreak, given incidence or case count data. We adjust the initialization and parametrization of a disease model and show that this allows us to determine systematic model bias. In addition, we provide a way to determine where the model diverges from observation and evaluate forecast accuracy. Wikipedia article access logs are shown to be highly correlated with historical ILI records and allow for accurate prediction of ILI data several weeks before it becomes available. The results show that prior to the peak of the flu season, our forecasting method produced 50% and 95% credible intervals for the 2013-2014 ILI observations that contained the actual observations for most weeks in the forecast. However, since our model does not account for re-infection or multiple strains of influenza, the tail of the epidemic is not predicted well after the peak of flu season has passed.",2015 May 14,"['Hickmann, Kyle S.', 'Fairchild, Geoffrey', 'Priedhorsky, Reid', 'Generous, Nicholas', 'Hyman, James M.', 'Deshpande, Alina', 'Del Valle, Sara Y.']",PLoS Comput Biol,,,True
0b3baf8685f86b7d620418cb17d29a60ce1d498a,PMC,Transcriptional Profiling of Host Gene Expression in Chicken Embryo Fibroblasts Infected with Reticuloendotheliosis Virus Strain HA1101,http://dx.doi.org/10.1371/journal.pone.0126992,PMC4431687,25973612,CC BY,"Reticuloendotheliosis virus (REV), a member of the Gammaretrovirus genus in the Retroviridae family, causes an immunosuppressive, oncogenic and runting-stunting syndrome in multiple avian hosts. To better understand the host interactions at the transcriptional level, microarray data analysis was performed in chicken embryo fibroblast cells at 1, 3, 5, and 7 days after infection with REV. This study identified 1,785 differentially expressed genes that were classified into several functional groups including signal transduction, immune response, biological adhesion and endocytosis. Significant differences were mainly observed in the expression of genes involved in the immune response, especially during the later post-infection time points. These results revealed that differentially expressed genes IL6, STAT1, MyD88, TLRs, NF-κB, IRF-7, and ISGs play important roles in the pathogenicity of REV infection. Our study is the first to use microarray analysis to investigate REV, and these findings provide insights into the underlying mechanisms of the host antiviral response and the molecular basis of viral pathogenesis.",2015 May 14,"['Miao, Ji', 'Bao, Yanqing', 'Ye, Jianqiang', 'Shao, Hongxia', 'Qian, Kun', 'Qin, Aijian']",PLoS One,,,True
7b430982b2fc7bb7b3e56ad2b58bb42a431985f6,PMC,Antimicrobial Air Filters Using Natural Euscaphis japonica Nanoparticles,http://dx.doi.org/10.1371/journal.pone.0126481,PMC4431859,25974109,CC BY,"Controlling bioaerosols has become more important with increasing participation in indoor activities. Treatments using natural-product nanomaterials are a promising technique because of their relatively low toxicity compared to inorganic nanomaterials such as silver nanoparticles or carbon nanotubes. In this study, antimicrobial filters were fabricated from natural Euscaphis japonica nanoparticles, which were produced by nebulizing E. japonica extract. The coated filters were assessed in terms of pressure drop, antimicrobial activity, filtration efficiency, major chemical components, and cytotoxicity. Pressure drop and antimicrobial activity increased as a function of nanoparticle deposition time (590, 855, and 1150 µg/cm2(filter) at 3-, 6-, and 9-min depositions, respectively). In filter tests, the antimicrobial efficacy was greater against Staphylococcus epidermidis than Micrococcus luteus; ~61, ~73, and ~82% of M. luteus cells were inactivated on filters that had been coated for 3, 6, and 9 min, respectively, while the corresponding values were ~78, ~88, and ~94% with S. epidermidis. Although statistically significant differences in filtration performance were not observed between samples as a function of deposition time, the average filtration efficacy was slightly higher for S. epidermidis aerosols (~97%) than for M. luteus aerosols (~95%). High-performance liquid chromatography (HPLC) and electrospray ionization-tandem mass spectrometry (ESI/MS) analyses confirmed that the major chemical compounds in the E. japonica extract were 1(ß)-O-galloyl pedunculagin, quercetin-3-O-glucuronide, and kaempferol-3-O-glucoside. In vitro cytotoxicity and disk diffusion tests showed that E. japonica nanoparticles were less toxic and exhibited stronger antimicrobial activity toward some bacterial strains than a reference soluble nickel compound, which is classified as a human carcinogen. This study provides valuable information for the development of a bioaerosol control system that is environmental friendly and suitable for use in indoor environments.",2015 May 14,"['Hwang, Gi Byoung', 'Heo, Ki Joon', 'Yun, Ji Ho', 'Lee, Jung Eun', 'Lee, Hee Ju', 'Nho, Chu Won', 'Bae, Gwi- Nam', 'Jung, Jae Hee']",PLoS One,,,True
d3507b9c61a3a5cd568e7f94bc6c99506dd9c152,PMC,Evidence for Human Norovirus Infection of Dogs in the United Kingdom,http://dx.doi.org/10.1128/JCM.02778-14,PMC4432062,25832298,CC BY,"Human noroviruses (HuNoVs) are a major cause of viral gastroenteritis, with an estimated 3 million cases per year in the United Kingdom. HuNoVs have recently been isolated from pet dogs in Europe (M. Summa, C.-H. von Bonsdorff, and L. Maunula, J Clin Virol 53:244–247, 2012, http://dx.doi.org/10.1016/j.jcv.2011.12.014), raising concerns about potential zoonotic infections. With 31% of United Kingdom households owning a dog, this could prove to be an important transmission route. To examine this risk, canine tissues were studied for their ability to bind to HuNoV in vitro. In addition, canine stool samples were analyzed for the presence of viral nucleic acid, and canine serum samples were tested for the presence of anti-HuNoV antibodies. The results showed that seven different genotypes of HuNoV virus-like particles (VLPs) can bind to canine gastrointestinal tissue, suggesting that infection is at least theoretically possible. Although HuNoV RNA was not identified in stool samples from 248 dogs, serological evidence of previous exposure to HuNoV was obtained in 43/325 canine serum samples. Remarkably, canine seroprevalence for different HuNoV genotypes mirrored the seroprevalence in the human population. Though entry and replication within cells have not been demonstrated, the canine serological data indicate that dogs produce an immune response to HuNoV, implying productive infection. In conclusion, this study reveals zoonotic implications for HuNoV, and to elucidate the significance of this finding, further epidemiological and molecular investigations will be essential.",2015 Jun 14,"['Caddy, Sarah L.', 'de Rougemont, Alexis', 'Emmott, Edward', 'El-Attar, Laila', 'Mitchell, Judy A.', 'Hollinshead, Michael', 'Belliot, Gael', 'Brownlie, Joe', 'Le Pendu, Jacques', 'Goodfellow, Ian']",J Clin Microbiol,,,False
bb76fcd0194eeda7dc70702dacad97492a497bea,PMC,Evidence for Human Norovirus Infection of Dogs in the United Kingdom,http://dx.doi.org/10.1128/JCM.02778-14,PMC4432062,25832298,CC BY,"Human noroviruses (HuNoVs) are a major cause of viral gastroenteritis, with an estimated 3 million cases per year in the United Kingdom. HuNoVs have recently been isolated from pet dogs in Europe (M. Summa, C.-H. von Bonsdorff, and L. Maunula, J Clin Virol 53:244–247, 2012, http://dx.doi.org/10.1016/j.jcv.2011.12.014), raising concerns about potential zoonotic infections. With 31% of United Kingdom households owning a dog, this could prove to be an important transmission route. To examine this risk, canine tissues were studied for their ability to bind to HuNoV in vitro. In addition, canine stool samples were analyzed for the presence of viral nucleic acid, and canine serum samples were tested for the presence of anti-HuNoV antibodies. The results showed that seven different genotypes of HuNoV virus-like particles (VLPs) can bind to canine gastrointestinal tissue, suggesting that infection is at least theoretically possible. Although HuNoV RNA was not identified in stool samples from 248 dogs, serological evidence of previous exposure to HuNoV was obtained in 43/325 canine serum samples. Remarkably, canine seroprevalence for different HuNoV genotypes mirrored the seroprevalence in the human population. Though entry and replication within cells have not been demonstrated, the canine serological data indicate that dogs produce an immune response to HuNoV, implying productive infection. In conclusion, this study reveals zoonotic implications for HuNoV, and to elucidate the significance of this finding, further epidemiological and molecular investigations will be essential.",2015 Jun 14,"['Caddy, Sarah L.', 'de Rougemont, Alexis', 'Emmott, Edward', 'El-Attar, Laila', 'Mitchell, Judy A.', 'Hollinshead, Michael', 'Belliot, Gael', 'Brownlie, Joe', 'Le Pendu, Jacques', 'Goodfellow, Ian']",J Clin Microbiol,,,True
7a7e072c8c70ce3f42148a4a4bbbc8800b2a03f2,PMC,Strand-Specific Quantitative Reverse Transcription-Polymerase Chain Reaction Assay for Measurement of Arenavirus Genomic and Antigenomic RNAs,http://dx.doi.org/10.1371/journal.pone.0120043,PMC4433285,25978311,CC BY,"Arenaviruses are bi-segmented, single-stranded RNA viruses that cause significant human disease. The manner in which they regulate the replication of their genome is not well-understood. This is partly due to the absence of a highly sensitive assay to measure individual species of arenavirus replicative RNAs. To overcome this obstacle, we designed a quantitative reverse transcription (RT)-PCR assay for selective quantitation of each of the lymphocytic choriomeningitis virus (LCMV) genomic or antigenomic RNAs. During the course of assay design, we identified a nonspecific priming phenomenon whereby, in the absence of an RT primer, cDNAs complementary to each of the LCMV replicative RNA species are generated during RT. We successfully circumvented this nonspecific priming event through the use of biotinylated primers in the RT reaction, which permitted affinity purification of primer-specific cDNAs using streptavidin-coated magnetic beads. As proof of principle, we used the assay to map the dynamics of LCMV replication at acute and persistent time points and to determine the quantities of genomic and antigenomic RNAs that are incorporated into LCMV particles. This assay can be adapted to measure total S or L segment-derived viral RNAs and therefore represents a highly sensitive diagnostic platform to screen for LCMV infection in rodent and human tissue samples and can also be used to quantify virus-cell attachment.",2015 May 15,"['Haist, Kelsey', 'Ziegler, Christopher', 'Botten, Jason']",PLoS One,,,True
42f6f50759cb4c433e8c1ff0d695bdb32ae97df9,PMC,plethy: management of whole body plethysmography data in R,http://dx.doi.org/10.1186/s12859-015-0547-7,PMC4434826,25924931,CC BY,"BACKGROUND: Characterization of respiratory phenotypes can enhance complex trait and genomic studies involving allergic/autoimmune and infectious diseases. Many aspects of respiration can be measured using devices known as plethysmographs that can measure thoracic movement. One such approach (the Buxco platform) performs unrestrained whole body plethysmography on mice which infers thoracic movements from pressure differences from the act of inhalation and exhalation. While proprietary software is available to perform basic statistical analysis as part of machine’s bundled software, it is desirable to be able to incorporate these analyses into high-throughput pipelines and integrate them with other data types, as well as leverage the wealth of analytic and visualization approaches provided by the R statistical computing environment. RESULTS: This manuscript describes the plethy package which is an R/Bioconductor framework for pre-processing and analysis of plethysmography data with emphasis on larger scale longitudinal experiments. The plethy package was designed to facilitate quality control and exploratory data analysis. We provide a demonstration of the features of plethy using a dataset assessing the respiratory effects over time of SARS and Influenza infection in mice. CONCLUSION: The plethy package provides functionality for users to import, perform quality assessment and exploratory data analysis in a manner that allows interoperability with existing modelling tools. Our package is implemented in R and is freely available as part of the Bioconductor project http://www.bioconductor.org/packages/release/bioc/html/plethy.html. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0547-7) contains supplementary material, which is available to authorized users.",2015 Apr 29,"['Bottomly, Daniel', 'Wilmot, Beth', 'McWeeney, Shannon K']",BMC Bioinformatics,,,True
8f240d93eda7d04def440b93acf64e41910f4e7c,PMC,plethy: management of whole body plethysmography data in R,http://dx.doi.org/10.1186/s12859-015-0547-7,PMC4434826,25924931,CC BY,"BACKGROUND: Characterization of respiratory phenotypes can enhance complex trait and genomic studies involving allergic/autoimmune and infectious diseases. Many aspects of respiration can be measured using devices known as plethysmographs that can measure thoracic movement. One such approach (the Buxco platform) performs unrestrained whole body plethysmography on mice which infers thoracic movements from pressure differences from the act of inhalation and exhalation. While proprietary software is available to perform basic statistical analysis as part of machine’s bundled software, it is desirable to be able to incorporate these analyses into high-throughput pipelines and integrate them with other data types, as well as leverage the wealth of analytic and visualization approaches provided by the R statistical computing environment. RESULTS: This manuscript describes the plethy package which is an R/Bioconductor framework for pre-processing and analysis of plethysmography data with emphasis on larger scale longitudinal experiments. The plethy package was designed to facilitate quality control and exploratory data analysis. We provide a demonstration of the features of plethy using a dataset assessing the respiratory effects over time of SARS and Influenza infection in mice. CONCLUSION: The plethy package provides functionality for users to import, perform quality assessment and exploratory data analysis in a manner that allows interoperability with existing modelling tools. Our package is implemented in R and is freely available as part of the Bioconductor project http://www.bioconductor.org/packages/release/bioc/html/plethy.html. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0547-7) contains supplementary material, which is available to authorized users.",2015 Apr 29,"['Bottomly, Daniel', 'Wilmot, Beth', 'McWeeney, Shannon K']",BMC Bioinformatics,,,True
29621887690af716dac0c244eeb95bce74fa8755,PMC,Mast Cells and Influenza A Virus: Association with Allergic Responses and Beyond,http://dx.doi.org/10.3389/fimmu.2015.00238,PMC4435071,26042121,CC BY,"Influenza A virus (IAV) is a widespread infectious agent commonly found in mammalian and avian species. In humans, IAV is a respiratory pathogen that causes seasonal infections associated with significant morbidity in young and elderly populations, and has a large economic impact. Moreover, IAV has the potential to cause both zoonotic spillover infection and global pandemics, which have significantly greater morbidity and mortality across all ages. The pathology associated with these pandemic and spillover infections appear to be the result of an excessive inflammatory response leading to severe lung damage, which likely predisposes the lungs for secondary bacterial infections. The lung is protected from pathogens by alveolar epithelial cells, endothelial cells, tissue resident alveolar macrophages, dendritic cells, and mast cells. The importance of mast cells during bacterial and parasitic infections has been extensively studied; yet, the role of these hematopoietic cells during viral infections is only beginning to emerge. Recently, it has been shown that mast cells can be directly activated in response to IAV, releasing mediators such histamine, proteases, leukotrienes, inflammatory cytokines, and antiviral chemokines, which participate in the excessive inflammatory and pathological response observed during IAV infections. In this review, we will examine the relationship between mast cells and IAV, and discuss the role of mast cells as a potential drug target during highly pathological IAV infections. Finally, we proposed an emerging role for mast cells in other viral infections associated with significant host pathology.",2015 May 18,"['Graham, Amy C.', 'Temple, Rachel M.', 'Obar, Joshua J.']",Front Immunol,,,True
7de0d0ac71e79cba5b50ed89303cae6d89bb0130,PMC,Multiplexed Component Analysis to Identify Genes Contributing to the Immune Response during Acute SIV Infection,http://dx.doi.org/10.1371/journal.pone.0126843,PMC4436129,25984721,CC BY,"Immune response genes play an important role during acute HIV and SIV infection. Using an SIV macaque model of AIDS and CNS disease, our overall goal was to assess how the expression of genes associated with immune and inflammatory responses are longitudinally changed in different organs or cells during SIV infection. To compare RNA expression of a panel of 88 immune-related genes across time points and among three tissues – spleen, mesenteric lymph nodes (MLN) and peripheral blood mononuclear cells (PBMC) – we designed a set of Nanostring probes. To identify significant genes during acute SIV infection and to investigate whether these genes are tissue-specific or have global roles, we introduce a novel multiplexed component analysis (MCA) method. This combines multivariate analysis methods with multiple preprocessing methods to create a set of 12 “judges”; each judge emphasizes particular types of change in gene expression to which cells could respond, for example, the absolute or relative size of expression change from baseline. Compared to bivariate analysis methods, our MCA method improved classification rates. This analysis allows us to identify three categories of genes: (a) consensus genes likely to contribute highly to the immune response; (b) genes that would contribute highly to the immune response only if certain assumptions are met – e.g. that the cell responds to relative expression change rather than absolute expression change; and (c) genes whose contribution to immune response appears to be modest. We then compared the results across the three tissues of interest; some genes are consistently highly-contributing in all tissues, while others are specific for certain tissues. Our analysis identified CCL8, CXCL10, CXCL11, MxA, OAS2, and OAS1 as top contributing genes, all of which are stimulated by type I interferon. This suggests that the cytokine storm during acute SIV infection is a systemic innate immune response against viral replication. Furthermore, these genes have approximately equal contributions to all tissues, making them possible candidates to be used as non-invasive biomarkers in studying PBMCs instead of MLN and spleen during acute SIV infection experiments. We identified clusters of genes that co-vary together and studied their correlation with regard to other gene clusters. We also developed novel methods to faithfully visualize multi-gene correlations on two-dimensional polar plots, and to visualize tissue specificity of gene expression responses.",2015 May 18,"['Hosseini, Iraj', 'Gama, Lucio', 'Mac Gabhann, Feilim']",PLoS One,,,True
a3a2b5d607691f30dd1b1baeca0e41817e2fde86,PMC,Designation of a Novel DKK1 Multiepitope DNA Vaccine and Inhibition of Bone Loss in Collagen-Induced Arthritic Mice,http://dx.doi.org/10.1155/2015/765490,PMC4436448,26075259,CC BY,"Dickkopf-1 (DKK1), a secretory inhibitor of canonical Wnt signaling, plays a critical role in certain bone loss diseases. Studies have shown that serum levels of DKK1 are significantly higher in rheumatoid arthritis (RA) patients and are correlated with the severity of the disease, which indicates the possibility that bone erosion in RA may be inhibited by neutralizing the biological activity of DKK1. In this study, we selected a panel of twelve peptides using the software DNASTAR 7.1 and screened high affinity and immunogenicity epitopes in vitro and in vivo assays. Furthermore, we optimized four B cell epitopes to design a novel DKK1 multiepitope DNA vaccine and evaluated its bone protective effects in collagen-induced arthritis (CIA), a mouse model of RA. High level expression of the designed vaccine was measured in supernatant of COS7 cells. In addition, intramuscular immunization of BALB/c mice with this vaccine was also highly expressed and sufficient to induce the production of long-term IgG, which neutralized natural DKK1 in vivo. Importantly, this vaccine significantly attenuated bone erosion in CIA mice compared with positive control mice. These results provide evidence for the development of a DNA vaccine targeted against DKK1 to attenuate bone erosion.",2015 May 5,"['Zhang, Xiaoqing', 'Liu, Sibo', 'Li, Shentao', 'Du, Yuxuan', 'Dou, Yunpeng', 'Li, Zhanguo', 'Yuan, Huihui', 'Zhao, Wenming']",Biomed Res Int,,,True
5934262a2b502aa5c1312dca72507395da00ccbe,PMC,Neopterin in Diagnosis and Monitoring of Infectious Diseases,http://dx.doi.org/10.1155/2013/196432,PMC4437389,26317013,CC BY,"Neopterin is produced by activated monocytes, macrophages, and dendritic cells upon stimulation by interferon gamma produced by T-lymphocytes. Quantification of neopterin in body fluids has been achieved by standard high-performance liquid chromatography, radioimmunoassays, and enzyme-linked immunosorbent assays. Neopterin levels predict HIV-related mortality more efficiently than clinical manifestations. Successful highly active antiretroviral therapy is associated with a decrease in neopterin levels. Elevated neopterin levels were associated with hepatitis by hepatitis A, B, and C viruses. Serum neopterin levels were found to be a predictor of response to treatment of chronic HCV infection with pegylated interferon combined with ribavirin. Neopterin levels of patients with pulmonary tuberculosis were found to be higher in patients with more extensive radiological changes. Elimination of blood donors with elevated neopterin levels to reduce risk of transmission of infections with known and unknown viral pathogens has been undertaken. Neopterin measurement is hereby more cost effective but less sensitive than screening using polymerase chain reaction based assays. In conclusion neopterin is a nonspecific marker of activated T-helper cell 1 dominated immune response. It may be a useful marker for monitoring of infectious disease activity during treatment and for more accurate estimation of extent of disease and prognosis.",2013 Dec 8,"Eisenhut, Michael",J Biomark,,,True
b5af7319ee1fd5e9cc3cf8c5836b19a408ac519b,PMC,Inhibition of a Putative Dihydropyrimidinase from Pseudomonas aeruginosa PAO1 by Flavonoids and Substrates of Cyclic Amidohydrolases,http://dx.doi.org/10.1371/journal.pone.0127634,PMC4437985,25993634,CC BY,"Dihydropyrimidinase is a member of the cyclic amidohydrolase family, which also includes allantoinase, dihydroorotase, hydantoinase, and imidase. These metalloenzymes possess very similar active sites and may use a similar mechanism for catalysis. However, whether the substrates and inhibitors of other cyclic amidohydrolases can inhibit dihydropyrimidinase remains unclear. This study investigated the inhibition of dihydropyrimidinase by flavonoids and substrates of other cyclic amidohydrolases. Allantoin, dihydroorotate, 5-hydantoin acetic acid, acetohydroxamate, orotic acid, and 3-amino-1,2,4-triazole could slightly inhibit dihydropyrimidinase, and the IC(50) values of these compounds were within the millimolar range. The inhibition of dihydropyrimidinase by flavonoids, such as myricetin, quercetin, kaempferol, galangin, dihydromyricetin, and myricitrin, was also investigated. Some of these compounds are known as inhibitors of allantoinase and dihydroorotase. Although the inhibitory effects of these flavonoids on dihydropyrimidinase were substrate-dependent, dihydromyricetin significantly inhibited dihydropyrimidinase with IC(50) values of 48 and 40 μM for the substrates dihydrouracil and 5-propyl-hydantoin, respectively. The results from the Lineweaver−Burk plot indicated that dihydromyricetin was a competitive inhibitor. Results from fluorescence quenching analysis indicated that dihydromyricetin could form a stable complex with dihydropyrimidinase with the K (d) value of 22.6 μM. A structural study using PatchDock showed that dihydromyricetin was docked in the active site pocket of dihydropyrimidinase, which was consistent with the findings from kinetic and fluorescence studies. This study was the first to demonstrate that naturally occurring product dihydromyricetin inhibited dihydropyrimidinase, even more than the substrate analogs (>3 orders of magnitude). These flavonols, particularly myricetin, may serve as drug leads and dirty drugs (for multiple targets) for designing compounds that target several cyclic amidohydrolases.",2015 May 19,"Huang, Cheng-Yang",PLoS One,,,True
a4efe5912760797318110dec69b255d743f0f0bd,PMC,CXCR2 is essential for cerebral endothelial activation and leukocyte recruitment during neuroinflammation,http://dx.doi.org/10.1186/s12974-015-0316-6,PMC4438521,25990934,CC BY,"BACKGROUND: Chemokines and chemokine receptors cooperate to promote immune cell recruitment to the central nervous system (CNS). In this study, we investigated the roles of CXCR2 and CXCL1 in leukocyte recruitment to the CNS using a murine model of neuroinflammation. METHODS: Wild-type (WT), CXCL1(−/−), and CXCR2(−/−) mice each received an intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS). Esterase staining and intravital microscopy were performed to examine neutrophil recruitment to the brain. To assess endothelial activation in these mice, the expression of adhesion molecules was measured via quantitative real-time polymerase chain reaction (PCR) and Western blotting. To identify the cellular source of functional CXCR2, chimeric mice were generated by transferring bone marrow cells between the WT and CXCR2(−/−) mice. RESULTS: Expression levels of the chemokines CXCL1, CXCL2, and CXCL5 were significantly increased in the brain following the i.c.v. injection of LPS. CXCR2 or CXCL1 deficiency blocked neutrophil infiltration and leukocyte recruitment in the cerebral microvessels. In the CXCR2(−/−) and CXCL1(−/−) mice, the cerebral endothelial expression of adhesion molecules such as P-selectin and VCAM-1 was dramatically reduced. Furthermore, the bone marrow transfer experiments demonstrated that CXCR2 expression on CNS-residing cells is essential for cerebral endothelial activation and leukocyte recruitment. Compared with microglia, cultured astrocytes secreted a much higher level of CXCL1 in vitro. Astrocyte culture conditioned medium significantly increased the expression of VCAM-1 and ICAM-1 in cerebral endothelial cells in a CXCR2-dependent manner. Additionally, CXCR2 messenger RNA (mRNA) expression in cerebral endothelial cells but not in microglia or astrocytes was increased following tumor necrosis factor-α (TNF-α) stimulation. The intravenous injection of the CXCR2 antagonist SB225002 significantly inhibited endothelial activation and leukocyte recruitment to cerebral microvessels. CONCLUSIONS: CXCL1 secreted by astrocytes and endothelial CXCR2 play essential roles in cerebral endothelial activation and subsequent leukocyte recruitment during neuroinflammation.",2015 May 21,"['Wu, Fengjiao', 'Zhao, Yawei', 'Jiao, Tian', 'Shi, Dongyan', 'Zhu, Xingxing', 'Zhang, Mingshun', 'Shi, Meiqing', 'Zhou, Hong']",J Neuroinflammation,,,True
a093f4ef60a47e5419181f6826ad4a45af198056,PMC,"Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections",http://dx.doi.org/10.1371/journal.ppat.1004900,PMC4438980,25993603,CC BY,"Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.",2015 May 20,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Chang, Li-Wen', 'Sanders, Chris', 'Hawkins, Michelle G.', 'Guzman, David S-M.', 'Drazenovich, Tracy', 'Dunker, Freeland', 'Kamaka, Elizabeth K.', 'Fisher, Debbie', 'Reavill, Drury R.', 'Meola, Linda F.', 'Levens, Gregory', 'DeRisi, Joseph L.']",PLoS Pathog,,,True
400d460a24bbc4165f5185484aa02807725d8d2c,PMC,"Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections",http://dx.doi.org/10.1371/journal.ppat.1004900,PMC4438980,25993603,CC BY,"Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.",2015 May 20,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Chang, Li-Wen', 'Sanders, Chris', 'Hawkins, Michelle G.', 'Guzman, David S-M.', 'Drazenovich, Tracy', 'Dunker, Freeland', 'Kamaka, Elizabeth K.', 'Fisher, Debbie', 'Reavill, Drury R.', 'Meola, Linda F.', 'Levens, Gregory', 'DeRisi, Joseph L.']",PLoS Pathog,,,False
f098138b4f4c09010693258de4211f968b8b4481,PMC,"Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections",http://dx.doi.org/10.1371/journal.ppat.1004900,PMC4438980,25993603,CC BY,"Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.",2015 May 20,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Chang, Li-Wen', 'Sanders, Chris', 'Hawkins, Michelle G.', 'Guzman, David S-M.', 'Drazenovich, Tracy', 'Dunker, Freeland', 'Kamaka, Elizabeth K.', 'Fisher, Debbie', 'Reavill, Drury R.', 'Meola, Linda F.', 'Levens, Gregory', 'DeRisi, Joseph L.']",PLoS Pathog,,,False
e4cecbeafb7ae61db981f0a3d22e07e55a41166b,PMC,"Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections",http://dx.doi.org/10.1371/journal.ppat.1004900,PMC4438980,25993603,CC BY,"Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.",2015 May 20,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Chang, Li-Wen', 'Sanders, Chris', 'Hawkins, Michelle G.', 'Guzman, David S-M.', 'Drazenovich, Tracy', 'Dunker, Freeland', 'Kamaka, Elizabeth K.', 'Fisher, Debbie', 'Reavill, Drury R.', 'Meola, Linda F.', 'Levens, Gregory', 'DeRisi, Joseph L.']",PLoS Pathog,,,False
0f316dba030fe5b826013e64b2b458fab695c9fb,PMC,"Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections",http://dx.doi.org/10.1371/journal.ppat.1004900,PMC4438980,25993603,CC BY,"Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.",2015 May 20,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Chang, Li-Wen', 'Sanders, Chris', 'Hawkins, Michelle G.', 'Guzman, David S-M.', 'Drazenovich, Tracy', 'Dunker, Freeland', 'Kamaka, Elizabeth K.', 'Fisher, Debbie', 'Reavill, Drury R.', 'Meola, Linda F.', 'Levens, Gregory', 'DeRisi, Joseph L.']",PLoS Pathog,,,False
8fd4e79d6b5ecf52f1649507df71ca75b64fcd34,PMC,"Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections",http://dx.doi.org/10.1371/journal.ppat.1004900,PMC4438980,25993603,CC BY,"Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.",2015 May 20,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Chang, Li-Wen', 'Sanders, Chris', 'Hawkins, Michelle G.', 'Guzman, David S-M.', 'Drazenovich, Tracy', 'Dunker, Freeland', 'Kamaka, Elizabeth K.', 'Fisher, Debbie', 'Reavill, Drury R.', 'Meola, Linda F.', 'Levens, Gregory', 'DeRisi, Joseph L.']",PLoS Pathog,,,False
2d1caa039267b86b3d4c4070dd72e0a389d70bf2,PMC,"Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections",http://dx.doi.org/10.1371/journal.ppat.1004900,PMC4438980,25993603,CC BY,"Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.",2015 May 20,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Chang, Li-Wen', 'Sanders, Chris', 'Hawkins, Michelle G.', 'Guzman, David S-M.', 'Drazenovich, Tracy', 'Dunker, Freeland', 'Kamaka, Elizabeth K.', 'Fisher, Debbie', 'Reavill, Drury R.', 'Meola, Linda F.', 'Levens, Gregory', 'DeRisi, Joseph L.']",PLoS Pathog,,,False
2002a6ed2eeda2b94a2db6292ef19098088f2f04,PMC,"Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections",http://dx.doi.org/10.1371/journal.ppat.1004900,PMC4438980,25993603,CC BY,"Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.",2015 May 20,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Chang, Li-Wen', 'Sanders, Chris', 'Hawkins, Michelle G.', 'Guzman, David S-M.', 'Drazenovich, Tracy', 'Dunker, Freeland', 'Kamaka, Elizabeth K.', 'Fisher, Debbie', 'Reavill, Drury R.', 'Meola, Linda F.', 'Levens, Gregory', 'DeRisi, Joseph L.']",PLoS Pathog,,,False
3236c24e4656add3fbf17ed686d2b7c73bb52de9,PMC,Detection of Acute HIV-1 Infection by RT-LAMP,http://dx.doi.org/10.1371/journal.pone.0126609,PMC4439053,25993381,CC0,"A rapid, cost-effective diagnostic test for the detection of acute HIV-1 infection is highly desired. Isothermal amplification techniques, such as reverse-transcription loop-mediated isothermal amplification (RT-LAMP), exhibit characteristics that are ideal for the development of a rapid nucleic acid amplification test (NAAT) because they are quick, easy to perform and do not require complex, dedicated equipment and laboratory space. In this study, we assessed the ability of the HIV-1 RT-LAMP assay to detect acute HIV infection as compared to a representative rapid antibody test and several FDA-approved laboratory-based assays. The HIV-1 RT-LAMP assay detected seroconverting individuals one to three weeks earlier than a rapid HIV antibody test and up to two weeks earlier than a lab-based antigen/antibody (Ag/Ab) combo enzyme immunoassay (EIA). RT-LAMP was not as sensitive as a lab-based qualitative RNA assay, which could be attributed to the significantly smaller nucleic acid input volume. To our knowledge, this is the first demonstration of detecting acute HIV infection using the RT-LAMP assay. The availability of a rapid NAAT, such as the HIV-1 RT-LAMP assay, at the point of care (POC) or in laboratories that do not have access to large platform NAAT could increase the percentage of individuals who receive an acute HIV infection status or confirmation of their HIV status, while immediately linking them to counseling and medical care. In addition, early knowledge of HIV status could lead to reduced high-risk behavior at a time when individuals are at a higher risk for transmitting the virus.",2015 May 20,"['Rudolph, Donna L.', 'Sullivan, Vickie', 'Owen, S. Michele', 'Curtis, Kelly A.']",PLoS One,,,True
9df0801be110f632c616bf9e91cb72d59383b086,PMC,Is Tuberculosis Treatment Really Free in China? A Study Comparing Two Areas with Different Management Models,http://dx.doi.org/10.1371/journal.pone.0126770,PMC4439067,25993411,CC BY,"OBJECTIVE: China has implemented a free-service policy for tuberculosis. However, patients still have to pay a substantial proportion of their annual income for treatment of this disease. This study describes the economic burden on patients with tuberculosis; identifies related factors by comparing two areas with different management models; and provides policy recommendation for tuberculosis control reform in China. METHODS: There are three tuberculosis management models in China: the tuberculosis dispensary model, specialist model and integrated model. We selected Zhangjiagang (ZJG) and Taixing (TX) as the study sites, which correspond to areas implementing the integrated model and dispensary model, respectively. Patients diagnosed and treated for tuberculosis since January 2010 were recruited as study subjects. A total of 590 patients (316 patients from ZJG and 274 patients from TX) were interviewed with a response rate of 81%. The economic burden attributed to tuberculosis, including direct costs and indirect costs, was estimated and compared between the two study sites. The Mann-Whitney U Test was used to compare the cost differences between the two groups. Potential factors related to the total out-of-pocket costs were analyzed based on a step-by-step multivariate linear regression model after the logarithmic transformation of the costs. RESULTS: The average (median, interquartile range) total cost was 18793.33 (9965, 3200-24400) CNY for patients in ZJG, which was significantly higher than for patients in TX (mean: 6598.33, median: 2263, interquartile range: 983–6688) (Z = 10.42, P < 0.001). After excluding expenses covered by health insurance, the average out-of-pocket costs were 14304.4 CNY in ZJG and 5639.2 CNY in TX. Based on the multivariable linear regression analysis, factors related to the total out-of-pocket costs were study site, age, number of clinical visits, residence, diagnosis delay, hospitalization, intake of liver protective drugs and use of the second-line drugs. CONCLUSION: Under the current “free of diagnosis and treatment” policy, the financial burden remains heavy on tuberculosis patients. Policy makers need to consider appropriate steps to lessen the burden of out-of-pocket costs for tuberculosis patients in China and how best to improve service delivery for poor patients.",2015 May 20,"['Qiu, Sangsang', 'Pan, Hongqiu', 'Zhang, Simin', 'Peng, Xianzhen', 'Zheng, Xianzhi', 'Xu, Guisheng', 'Wang, Min', 'Wang, Jianming', 'Lu, Hui']",PLoS One,,,True
bb61779140755a7d48b8d5ff6d848a07977b4af3,PMC,Correction: Chinese Social Media Reaction to Information about 42 Notifiable Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0129525,PMC4439074,25992906,CC BY,,2015 May 20,,PLoS One,,,False
d569871d337077bcb21c8c19fde422b0bca8e0c8,PMC,Viral Etiology of Chronic Obstructive Pulmonary Disease Exacerbations during the A/H1N1pdm09 Pandemic and Postpandemic Period,http://dx.doi.org/10.1155/2015/560679,PMC4439490,26064118,CC BY,"Viral infections are one of the main causes of acute exacerbations of chronic obstructive pulmonary disease (AE-COPD). Emergence of A/H1N1pdm influenza virus in the 2009 pandemic changed the viral etiology of exacerbations that were reported before the pandemic. The aim of this study was to describe the etiology of respiratory viruses in 195 Spanish patients affected by AE-COPD from the pandemic until the 2011-12 influenza epidemic. During the study period (2009–2012), respiratory viruses were identified in 48.7% of samples, and the proportion of viral detections in AE-COPD was higher in patients aged 30–64 years than ≥65 years. Influenza A viruses were the pathogens most often detected during the pandemic and the following two influenza epidemics in contradistinction to human rhino/enteroviruses that were the main viruses causing AE-COPD before the pandemic. The probability of influenza virus detection was 2.78-fold higher in patients who are 30–64 years old than those ≥65. Most respiratory samples were obtained during the pandemic, but the influenza detection rate was higher during the 2011-12 epidemic. There is a need for more accurate AE-COPD diagnosis, emphasizing the role of respiratory viruses. Furthermore, diagnosis requires increased attention to patient age and the characteristics of each influenza epidemic.",2015 May 7,"['Sanz, Ivan', 'Tamames, Sonia', 'Rojo, Silvia', 'Justel, Mar', 'Lozano, José Eugenio', 'Disdier, Carlos', 'Vega, Tomás', 'Ortiz de Lejarazu, Raúl']",Adv Virol,,,True
0bcbf352d92ce90e1c2595fb458ded32b45002a0,PMC,Human seroprevalence indicating hantavirus infections in tropical rainforests of Côte d’Ivoire and Democratic Republic of Congo,http://dx.doi.org/10.3389/fmicb.2015.00518,PMC4439549,26052326,CC BY,"Hantaviruses are members of the Bunyaviridae family carried by small mammals and causing human hemorrhagic fevers worldwide. In Western Africa, where a variety of hemorrhagic fever viruses occurs, indigenous hantaviruses have been molecularly found in animal reservoirs such as rodents, shrews, and bats since 2006. To investigate the human contact to hantaviruses carried by these hosts and to assess the public health relevance of hantaviruses for humans living in the tropical rainforest regions of Western and Central Africa, we performed a cross-sectional seroprevalence study in the region of Taï National Park in Côte d’Ivoire and the Bandundu region near the Salonga National Park in the Democratic Republic (DR) of Congo. Serum samples were initially screened with enzyme-linked immunosorbent assays using nucleoproteins of several hantaviruses as diagnostic antigens. Positive results were confirmed by Western blotting and immunofluorescence testing. Seroprevalence rates of 3.9% (27/687) and 2.4% (7/295), respectively, were found in the investigated regions in Côte d’Ivoire and the DR Congo. In Côte d’Ivoire, this value was significantly higher than the seroprevalence rates previously reported from the neighboring country Guinea as well as from South Africa. Our study indicates an exposure of humans to hantaviruses in West and Central African tropical rainforest areas. In order to pinpoint the possible existence and frequency of clinical disease caused by hantaviruses in this region of the world, systematic investigations of patients with fever and renal or respiratory symptoms are required.",2015 May 21,"['Witkowski, Peter T.', 'Leendertz, Siv A. J.', 'Auste, Brita', 'Akoua-Koffi, Chantal', 'Schubert, Grit', 'Klempa, Boris', 'Muyembe-Tamfum, Jean-Jacques', 'Karhemere, Stomy', 'Leendertz, Fabian H.', 'Krüger, Detlev H.']",Front Microbiol,,,True
f9410459142b63fb34eac0375dda7d9b6460b3fe,PMC,Persistent Foot-and-Mouth Disease Virus Infection in the Nasopharynx of Cattle; Tissue-Specific Distribution and Local Cytokine Expression,http://dx.doi.org/10.1371/journal.pone.0125698,PMC4440813,25996935,CC0,"Tissues obtained post-mortem from cattle persistently infected with foot-and-mouth disease virus (FMDV) were analyzed to characterize the tissue-specific localization of FMDV and partial transcriptome profiles for selected immunoregulatory cytokines. Analysis of 28 distinct anatomic sites from 21 steers infected with FMDV serotype A, O or SAT2, had the highest prevalence of overall viral detection in the dorsal nasopharynx (80.95%) and dorsal soft palate (71.43%). FMDV was less frequently detected in laryngeal mucosal tissues, oropharyngeal mucosal sites, and lymph nodes draining the pharynx. Immunomicroscopy indicated that within persistently infected mucosal tissues, FMDV antigens were rarely detectable within few epithelial cells in regions of mucosa-associated lymphoid tissue (MALT). Transcriptome analysis of persistently infected pharyngeal tissues by qRT-PCR for 14 cytokine genes indicated a general trend of decreased mRNA levels compared to uninfected control animals. Although, statistically significant differences were not observed, greatest suppression of relative expression (RE) was identified for IP-10 (RE = 0.198), IFN-β (RE = 0.269), IL-12 (RE = 0.275), and IL-2 (RE = 0.312). Increased relative expression was detected for IL-6 (RE = 2.065). Overall, this data demonstrates that during the FMDV carrier state in cattle, viral persistence is associated with epithelial cells of the nasopharynx in the upper respiratory tract and decreased levels of mRNA for several immunoregulatory cytokines in the infected tissues.",2015 May 21,"['Pacheco, Juan M.', 'Smoliga, George R.', 'O’Donnell, Vivian', 'Brito, Barbara P.', 'Stenfeldt, Carolina', 'Rodriguez, Luis L.', 'Arzt, Jonathan']",PLoS One,,,True
a9f21b4c08ef6cf4b7553c5666b4102d0c984243,PMC,Broad-spectrum antiviral agents,http://dx.doi.org/10.3389/fmicb.2015.00517,PMC4440912,26052325,CC BY,"Development of highly effective, broad-spectrum antiviral agents is the major objective shared by the fields of virology and pharmaceutics. Antiviral drug development has focused on targeting viral entry and replication, as well as modulating cellular defense system. High throughput screening of molecules, genetic engineering of peptides, and functional screening of agents have identified promising candidates for development of optimal broad-spectrum antiviral agents to intervene in viral infection and control viral epidemics. This review discusses current knowledge, prospective applications, opportunities, and challenges in the development of broad-spectrum antiviral agents.",2015 May 22,"['Zhu, Jun-Da', 'Meng, Wen', 'Wang, Xiao-Jia', 'Wang, Hwa-Chain R.']",Front Microbiol,,,True
ae99d270c1b2d2307c4375fecde1a037c263b507,PMC,"Complete Genome Sequence of a Porcine Epidemic Diarrhea Virus from a Novel Outbreak in Belgium, January 2015",http://dx.doi.org/10.1128/genomeA.00506-15,PMC4440965,25999551,CC BY,"Porcine epidemic diarrhea virus (PEDV) is a member of the family Coronaviridae and can cause severe outbreaks of diarrhea in piglets from different age groups. Here, we report the complete genome sequence (28,028 nt) of a PEDV strain isolated during a novel outbreak in Belgium.",2015 May 21,"['Theuns, Sebastiaan', 'Conceição-Neto, Nádia', 'Christiaens, Isaura', 'Zeller, Mark', 'Desmarets, Lowiese M. B.', 'Roukaerts, Inge D. M.', 'Acar, Delphine D.', 'Heylen, Elisabeth', 'Matthijnssens, Jelle', 'Nauwynck, Hans J.']",Genome Announc,,,True
5a85cf34eee367f1a73ac62a05779d4c815dc767,PMC,Interactions of Francisella tularensis with Alveolar Type II Epithelial Cells and the Murine Respiratory Epithelium,http://dx.doi.org/10.1371/journal.pone.0127458,PMC4444194,26010977,CC BY,"Francisella tularensis is classified as a Tier 1 select agent by the CDC due to its low infectious dose and the possibility that the organism can be used as a bioweapon. The low dose of infection suggests that Francisella is unusually efficient at evading host defenses. Although ~50 cfu are necessary to cause human respiratory infection, the early interactions of virulent Francisella with the lung environment are not well understood. To provide additional insights into these interactions during early Francisella infection of mice, we performed TEM analysis on mouse lungs infected with F. tularensis strains Schu S4, LVS and the O-antigen mutant Schu S4 waaY::TrgTn. For all three strains, the majority of the bacteria that we could detect were observed within alveolar type II epithelial cells at 16 hours post infection. Although there were no detectable differences in the amount of bacteria within an infected cell between the three strains, there was a significant increase in the amount of cellular debris observed in the air spaces of the lungs in the Schu S4 waaY::TrgTn mutant compared to either the Schu S4 or LVS strain. We also studied the interactions of Francisella strains with human AT-II cells in vitro by characterizing the ability of these three strains to invade and replicate within these cells. Gentamicin assay and confocal microscopy both confirmed that F. tularensis Schu S4 replicated robustly within these cells while F. tularensis LVS displayed significantly lower levels of growth over 24 hours, although the strain was able to enter these cells at about the same level as Schu S4 (1 organism per cell), as determined by confocal imaging. The Schu S4 waaY::TrgTn mutant that we have previously described as attenuated for growth in macrophages and mouse virulence displayed interesting properties as well. This mutant induced significant airway inflammation (cell debris) and had an attenuated growth phenotype in the human AT-II cells. These data extend our understanding of early Francisella infection by demonstrating that Francisella enter significant numbers of AT-II cells within the lung and that the capsule and LPS of wild type Schu S4 helps prevent murine lung damage during infection. Furthermore, our data identified that human AT-II cells allow growth of Schu S4, but these same cells supported poor growth of the attenuated LVS strain in vitro. Collectively, these data further our understanding of the role of AT-II cells in Francisella infections.",2015 May 26,"['Faron, Matthew', 'Fletcher, Joshua R.', 'Rasmussen, Jed A.', 'Apicella, Michael A.', 'Jones, Bradley D.']",PLoS One,,,True
4cd92be2bf6b804588415da689ae6afa8ef97099,PMC,Efficiency of Airborne Sample Analysis Platform (ASAP) bioaerosol sampler for pathogen detection,http://dx.doi.org/10.3389/fmicb.2015.00512,PMC4444837,26074900,CC BY,"The threat of bioterrorism and pandemics has highlighted the urgency for rapid and reliable bioaerosol detection in different environments. Safeguarding against such threats requires continuous sampling of the ambient air for pathogen detection. In this study we investigated the efficacy of the Airborne Sample Analysis Platform (ASAP) 2800 bioaerosol sampler to collect representative samples of air and identify specific viruses suspended as bioaerosols. To test this concept, we aerosolized an innocuous replication-defective bovine adenovirus serotype 3 (BAdV3) in a controlled laboratory environment. The ASAP efficiently trapped the surrogate virus at 5 × 10(3) plaque-forming units (p.f.u.) [2 × 10(5) genome copy equivalent] concentrations or more resulting in the successful detection of the virus using quantitative PCR. These results support the further development of ASAP for bioaerosol pathogen detection.",2015 May 27,"['Sharma, Anurag', 'Clark, Elizabeth', 'McGlothlin, James D.', 'Mittal, Suresh K.']",Front Microbiol,,,True
5d5edffd3b3213b480c77b6a06949a8a88618b69,PMC,Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned holstein calves,http://dx.doi.org/10.1186/1471-2164-15-1164,PMC4445561,25534905,CC BY,"BACKGROUND: Bovine respiratory disease complex (BRDC) is an infectious disease of cattle that is caused by a combination of viral and/or bacterial pathogens. Selection for cattle with reduced susceptibility to respiratory disease would provide a permanent tool for reducing the prevalence of BRDC. The objective of this study was to identify BRDC susceptibility loci in pre-weaned Holstein calves as a prerequisite to using genetic improvement as a tool for decreasing the prevalence of BRDC. High density SNP genotyping with the Illumina BovineHD BeadChip was conducted on 1257 male and 757 female Holstein calves from California (CA), and 767 calves identified as female from New Mexico (NM). Of these, 1382 were classified as BRDC cases, and 1396 were classified as controls, with all phenotypes assigned using the McGuirk health scoring system. During the acquisition of blood for DNA isolation, two deep pharyngeal and one mid-nasal diagnostic swab were obtained from each calf for the identification of bacterial and viral pathogens. Genome-wide association analyses were conducted using four analytical approaches (EIGENSTRAT, EMMAX-GRM, GBLUP and FvR). The most strongly associated SNPs from each individual analysis were ranked and evaluated for concordance. The heritability of susceptibility to BRDC in pre-weaned Holstein calves was estimated. RESULTS: The four statistical approaches produced highly concordant results for 373 top ranked SNPs that defined 126 chromosomal regions for the CA population. Similarly, in NM, 370 SNPs defined 138 genomic regions that were identified by all four approaches. When the two populations were combined (i.e., CA + NM) and analyzed, 324 SNPs defined 116 genomic regions that were associated with BRDC across all analytical methods. Heritability estimates for BRDC were 21% for both CA and NM as individual populations, but declined to 13% when the populations were combined. CONCLUSIONS: Four analytical approaches utilizing both single and multi-marker association methods revealed common genomic regions associated with BRDC susceptibility that can be further characterized and used for genomic selection. Moderate heritability estimates were observed for BRDC susceptibility in pre-weaned Holstein calves, thereby supporting the application of genomic selection to reduce the prevalence of BRDC in U.S. Holsteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1164) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Neibergs, Holly L', 'Seabury, Christopher M', 'Wojtowicz, Andrzej J', 'Wang, Zeping', 'Scraggs, Erik', 'Kiser, Jennifer N', 'Neupane, Mahesh', 'Womack, James E', 'Eenennaam, Alison Van', 'Hagevoort, Gerald Robert', 'Lehenbauer, Terry W', 'Aly, Sharif', 'Davis, Jessica', 'Taylor, Jeremy F', None]",BMC Genomics,,,True
f02e28bfe40a510818fba3cc0adc91d7dd1c3af3,PMC,Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned holstein calves,http://dx.doi.org/10.1186/1471-2164-15-1164,PMC4445561,25534905,CC BY,"BACKGROUND: Bovine respiratory disease complex (BRDC) is an infectious disease of cattle that is caused by a combination of viral and/or bacterial pathogens. Selection for cattle with reduced susceptibility to respiratory disease would provide a permanent tool for reducing the prevalence of BRDC. The objective of this study was to identify BRDC susceptibility loci in pre-weaned Holstein calves as a prerequisite to using genetic improvement as a tool for decreasing the prevalence of BRDC. High density SNP genotyping with the Illumina BovineHD BeadChip was conducted on 1257 male and 757 female Holstein calves from California (CA), and 767 calves identified as female from New Mexico (NM). Of these, 1382 were classified as BRDC cases, and 1396 were classified as controls, with all phenotypes assigned using the McGuirk health scoring system. During the acquisition of blood for DNA isolation, two deep pharyngeal and one mid-nasal diagnostic swab were obtained from each calf for the identification of bacterial and viral pathogens. Genome-wide association analyses were conducted using four analytical approaches (EIGENSTRAT, EMMAX-GRM, GBLUP and FvR). The most strongly associated SNPs from each individual analysis were ranked and evaluated for concordance. The heritability of susceptibility to BRDC in pre-weaned Holstein calves was estimated. RESULTS: The four statistical approaches produced highly concordant results for 373 top ranked SNPs that defined 126 chromosomal regions for the CA population. Similarly, in NM, 370 SNPs defined 138 genomic regions that were identified by all four approaches. When the two populations were combined (i.e., CA + NM) and analyzed, 324 SNPs defined 116 genomic regions that were associated with BRDC across all analytical methods. Heritability estimates for BRDC were 21% for both CA and NM as individual populations, but declined to 13% when the populations were combined. CONCLUSIONS: Four analytical approaches utilizing both single and multi-marker association methods revealed common genomic regions associated with BRDC susceptibility that can be further characterized and used for genomic selection. Moderate heritability estimates were observed for BRDC susceptibility in pre-weaned Holstein calves, thereby supporting the application of genomic selection to reduce the prevalence of BRDC in U.S. Holsteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1164) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Neibergs, Holly L', 'Seabury, Christopher M', 'Wojtowicz, Andrzej J', 'Wang, Zeping', 'Scraggs, Erik', 'Kiser, Jennifer N', 'Neupane, Mahesh', 'Womack, James E', 'Eenennaam, Alison Van', 'Hagevoort, Gerald Robert', 'Lehenbauer, Terry W', 'Aly, Sharif', 'Davis, Jessica', 'Taylor, Jeremy F', None]",BMC Genomics,,,False
d057621b1ac0ac1b494345f20d432f6f7a78760d,PMC,Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned holstein calves,http://dx.doi.org/10.1186/1471-2164-15-1164,PMC4445561,25534905,CC BY,"BACKGROUND: Bovine respiratory disease complex (BRDC) is an infectious disease of cattle that is caused by a combination of viral and/or bacterial pathogens. Selection for cattle with reduced susceptibility to respiratory disease would provide a permanent tool for reducing the prevalence of BRDC. The objective of this study was to identify BRDC susceptibility loci in pre-weaned Holstein calves as a prerequisite to using genetic improvement as a tool for decreasing the prevalence of BRDC. High density SNP genotyping with the Illumina BovineHD BeadChip was conducted on 1257 male and 757 female Holstein calves from California (CA), and 767 calves identified as female from New Mexico (NM). Of these, 1382 were classified as BRDC cases, and 1396 were classified as controls, with all phenotypes assigned using the McGuirk health scoring system. During the acquisition of blood for DNA isolation, two deep pharyngeal and one mid-nasal diagnostic swab were obtained from each calf for the identification of bacterial and viral pathogens. Genome-wide association analyses were conducted using four analytical approaches (EIGENSTRAT, EMMAX-GRM, GBLUP and FvR). The most strongly associated SNPs from each individual analysis were ranked and evaluated for concordance. The heritability of susceptibility to BRDC in pre-weaned Holstein calves was estimated. RESULTS: The four statistical approaches produced highly concordant results for 373 top ranked SNPs that defined 126 chromosomal regions for the CA population. Similarly, in NM, 370 SNPs defined 138 genomic regions that were identified by all four approaches. When the two populations were combined (i.e., CA + NM) and analyzed, 324 SNPs defined 116 genomic regions that were associated with BRDC across all analytical methods. Heritability estimates for BRDC were 21% for both CA and NM as individual populations, but declined to 13% when the populations were combined. CONCLUSIONS: Four analytical approaches utilizing both single and multi-marker association methods revealed common genomic regions associated with BRDC susceptibility that can be further characterized and used for genomic selection. Moderate heritability estimates were observed for BRDC susceptibility in pre-weaned Holstein calves, thereby supporting the application of genomic selection to reduce the prevalence of BRDC in U.S. Holsteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1164) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Neibergs, Holly L', 'Seabury, Christopher M', 'Wojtowicz, Andrzej J', 'Wang, Zeping', 'Scraggs, Erik', 'Kiser, Jennifer N', 'Neupane, Mahesh', 'Womack, James E', 'Eenennaam, Alison Van', 'Hagevoort, Gerald Robert', 'Lehenbauer, Terry W', 'Aly, Sharif', 'Davis, Jessica', 'Taylor, Jeremy F', None]",BMC Genomics,,,False
3258f0c4d9a0a3e68fabba3bd166a150c43ba6eb,PMC,Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned holstein calves,http://dx.doi.org/10.1186/1471-2164-15-1164,PMC4445561,25534905,CC BY,"BACKGROUND: Bovine respiratory disease complex (BRDC) is an infectious disease of cattle that is caused by a combination of viral and/or bacterial pathogens. Selection for cattle with reduced susceptibility to respiratory disease would provide a permanent tool for reducing the prevalence of BRDC. The objective of this study was to identify BRDC susceptibility loci in pre-weaned Holstein calves as a prerequisite to using genetic improvement as a tool for decreasing the prevalence of BRDC. High density SNP genotyping with the Illumina BovineHD BeadChip was conducted on 1257 male and 757 female Holstein calves from California (CA), and 767 calves identified as female from New Mexico (NM). Of these, 1382 were classified as BRDC cases, and 1396 were classified as controls, with all phenotypes assigned using the McGuirk health scoring system. During the acquisition of blood for DNA isolation, two deep pharyngeal and one mid-nasal diagnostic swab were obtained from each calf for the identification of bacterial and viral pathogens. Genome-wide association analyses were conducted using four analytical approaches (EIGENSTRAT, EMMAX-GRM, GBLUP and FvR). The most strongly associated SNPs from each individual analysis were ranked and evaluated for concordance. The heritability of susceptibility to BRDC in pre-weaned Holstein calves was estimated. RESULTS: The four statistical approaches produced highly concordant results for 373 top ranked SNPs that defined 126 chromosomal regions for the CA population. Similarly, in NM, 370 SNPs defined 138 genomic regions that were identified by all four approaches. When the two populations were combined (i.e., CA + NM) and analyzed, 324 SNPs defined 116 genomic regions that were associated with BRDC across all analytical methods. Heritability estimates for BRDC were 21% for both CA and NM as individual populations, but declined to 13% when the populations were combined. CONCLUSIONS: Four analytical approaches utilizing both single and multi-marker association methods revealed common genomic regions associated with BRDC susceptibility that can be further characterized and used for genomic selection. Moderate heritability estimates were observed for BRDC susceptibility in pre-weaned Holstein calves, thereby supporting the application of genomic selection to reduce the prevalence of BRDC in U.S. Holsteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1164) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Neibergs, Holly L', 'Seabury, Christopher M', 'Wojtowicz, Andrzej J', 'Wang, Zeping', 'Scraggs, Erik', 'Kiser, Jennifer N', 'Neupane, Mahesh', 'Womack, James E', 'Eenennaam, Alison Van', 'Hagevoort, Gerald Robert', 'Lehenbauer, Terry W', 'Aly, Sharif', 'Davis, Jessica', 'Taylor, Jeremy F', None]",BMC Genomics,,,False
fc366b1091121f8885d1d84e605c2353f2757c4c,PMC,Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned holstein calves,http://dx.doi.org/10.1186/1471-2164-15-1164,PMC4445561,25534905,CC BY,"BACKGROUND: Bovine respiratory disease complex (BRDC) is an infectious disease of cattle that is caused by a combination of viral and/or bacterial pathogens. Selection for cattle with reduced susceptibility to respiratory disease would provide a permanent tool for reducing the prevalence of BRDC. The objective of this study was to identify BRDC susceptibility loci in pre-weaned Holstein calves as a prerequisite to using genetic improvement as a tool for decreasing the prevalence of BRDC. High density SNP genotyping with the Illumina BovineHD BeadChip was conducted on 1257 male and 757 female Holstein calves from California (CA), and 767 calves identified as female from New Mexico (NM). Of these, 1382 were classified as BRDC cases, and 1396 were classified as controls, with all phenotypes assigned using the McGuirk health scoring system. During the acquisition of blood for DNA isolation, two deep pharyngeal and one mid-nasal diagnostic swab were obtained from each calf for the identification of bacterial and viral pathogens. Genome-wide association analyses were conducted using four analytical approaches (EIGENSTRAT, EMMAX-GRM, GBLUP and FvR). The most strongly associated SNPs from each individual analysis were ranked and evaluated for concordance. The heritability of susceptibility to BRDC in pre-weaned Holstein calves was estimated. RESULTS: The four statistical approaches produced highly concordant results for 373 top ranked SNPs that defined 126 chromosomal regions for the CA population. Similarly, in NM, 370 SNPs defined 138 genomic regions that were identified by all four approaches. When the two populations were combined (i.e., CA + NM) and analyzed, 324 SNPs defined 116 genomic regions that were associated with BRDC across all analytical methods. Heritability estimates for BRDC were 21% for both CA and NM as individual populations, but declined to 13% when the populations were combined. CONCLUSIONS: Four analytical approaches utilizing both single and multi-marker association methods revealed common genomic regions associated with BRDC susceptibility that can be further characterized and used for genomic selection. Moderate heritability estimates were observed for BRDC susceptibility in pre-weaned Holstein calves, thereby supporting the application of genomic selection to reduce the prevalence of BRDC in U.S. Holsteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1164) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Neibergs, Holly L', 'Seabury, Christopher M', 'Wojtowicz, Andrzej J', 'Wang, Zeping', 'Scraggs, Erik', 'Kiser, Jennifer N', 'Neupane, Mahesh', 'Womack, James E', 'Eenennaam, Alison Van', 'Hagevoort, Gerald Robert', 'Lehenbauer, Terry W', 'Aly, Sharif', 'Davis, Jessica', 'Taylor, Jeremy F', None]",BMC Genomics,,,False
d4faf81a864d265824ca6417fafec11f3b40ab15,PMC,Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned holstein calves,http://dx.doi.org/10.1186/1471-2164-15-1164,PMC4445561,25534905,CC BY,"BACKGROUND: Bovine respiratory disease complex (BRDC) is an infectious disease of cattle that is caused by a combination of viral and/or bacterial pathogens. Selection for cattle with reduced susceptibility to respiratory disease would provide a permanent tool for reducing the prevalence of BRDC. The objective of this study was to identify BRDC susceptibility loci in pre-weaned Holstein calves as a prerequisite to using genetic improvement as a tool for decreasing the prevalence of BRDC. High density SNP genotyping with the Illumina BovineHD BeadChip was conducted on 1257 male and 757 female Holstein calves from California (CA), and 767 calves identified as female from New Mexico (NM). Of these, 1382 were classified as BRDC cases, and 1396 were classified as controls, with all phenotypes assigned using the McGuirk health scoring system. During the acquisition of blood for DNA isolation, two deep pharyngeal and one mid-nasal diagnostic swab were obtained from each calf for the identification of bacterial and viral pathogens. Genome-wide association analyses were conducted using four analytical approaches (EIGENSTRAT, EMMAX-GRM, GBLUP and FvR). The most strongly associated SNPs from each individual analysis were ranked and evaluated for concordance. The heritability of susceptibility to BRDC in pre-weaned Holstein calves was estimated. RESULTS: The four statistical approaches produced highly concordant results for 373 top ranked SNPs that defined 126 chromosomal regions for the CA population. Similarly, in NM, 370 SNPs defined 138 genomic regions that were identified by all four approaches. When the two populations were combined (i.e., CA + NM) and analyzed, 324 SNPs defined 116 genomic regions that were associated with BRDC across all analytical methods. Heritability estimates for BRDC were 21% for both CA and NM as individual populations, but declined to 13% when the populations were combined. CONCLUSIONS: Four analytical approaches utilizing both single and multi-marker association methods revealed common genomic regions associated with BRDC susceptibility that can be further characterized and used for genomic selection. Moderate heritability estimates were observed for BRDC susceptibility in pre-weaned Holstein calves, thereby supporting the application of genomic selection to reduce the prevalence of BRDC in U.S. Holsteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1164) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Neibergs, Holly L', 'Seabury, Christopher M', 'Wojtowicz, Andrzej J', 'Wang, Zeping', 'Scraggs, Erik', 'Kiser, Jennifer N', 'Neupane, Mahesh', 'Womack, James E', 'Eenennaam, Alison Van', 'Hagevoort, Gerald Robert', 'Lehenbauer, Terry W', 'Aly, Sharif', 'Davis, Jessica', 'Taylor, Jeremy F', None]",BMC Genomics,,,False
b68d33bbec8af949490bf52a5b8dd215c2b37590,PMC,Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned holstein calves,http://dx.doi.org/10.1186/1471-2164-15-1164,PMC4445561,25534905,CC BY,"BACKGROUND: Bovine respiratory disease complex (BRDC) is an infectious disease of cattle that is caused by a combination of viral and/or bacterial pathogens. Selection for cattle with reduced susceptibility to respiratory disease would provide a permanent tool for reducing the prevalence of BRDC. The objective of this study was to identify BRDC susceptibility loci in pre-weaned Holstein calves as a prerequisite to using genetic improvement as a tool for decreasing the prevalence of BRDC. High density SNP genotyping with the Illumina BovineHD BeadChip was conducted on 1257 male and 757 female Holstein calves from California (CA), and 767 calves identified as female from New Mexico (NM). Of these, 1382 were classified as BRDC cases, and 1396 were classified as controls, with all phenotypes assigned using the McGuirk health scoring system. During the acquisition of blood for DNA isolation, two deep pharyngeal and one mid-nasal diagnostic swab were obtained from each calf for the identification of bacterial and viral pathogens. Genome-wide association analyses were conducted using four analytical approaches (EIGENSTRAT, EMMAX-GRM, GBLUP and FvR). The most strongly associated SNPs from each individual analysis were ranked and evaluated for concordance. The heritability of susceptibility to BRDC in pre-weaned Holstein calves was estimated. RESULTS: The four statistical approaches produced highly concordant results for 373 top ranked SNPs that defined 126 chromosomal regions for the CA population. Similarly, in NM, 370 SNPs defined 138 genomic regions that were identified by all four approaches. When the two populations were combined (i.e., CA + NM) and analyzed, 324 SNPs defined 116 genomic regions that were associated with BRDC across all analytical methods. Heritability estimates for BRDC were 21% for both CA and NM as individual populations, but declined to 13% when the populations were combined. CONCLUSIONS: Four analytical approaches utilizing both single and multi-marker association methods revealed common genomic regions associated with BRDC susceptibility that can be further characterized and used for genomic selection. Moderate heritability estimates were observed for BRDC susceptibility in pre-weaned Holstein calves, thereby supporting the application of genomic selection to reduce the prevalence of BRDC in U.S. Holsteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1164) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Neibergs, Holly L', 'Seabury, Christopher M', 'Wojtowicz, Andrzej J', 'Wang, Zeping', 'Scraggs, Erik', 'Kiser, Jennifer N', 'Neupane, Mahesh', 'Womack, James E', 'Eenennaam, Alison Van', 'Hagevoort, Gerald Robert', 'Lehenbauer, Terry W', 'Aly, Sharif', 'Davis, Jessica', 'Taylor, Jeremy F', None]",BMC Genomics,,,True
12aa5eeb50296d810121cc1b2f87f053c39ce204,PMC,Single amino acid substitution (G42E) in the receptor binding domain of mouse mammary tumour virus envelope protein facilitates infection of non-murine cells in a transferrin receptor 1-independent manner,http://dx.doi.org/10.1186/s12977-015-0168-2,PMC4445801,25980759,CC BY,"BACKGROUND: Mouse mammary tumour virus (MMTV) is a betaretrovirus that infects rodent cells and uses mouse tranferrin receptor 1 (TfR1) for cell entry. Several MMTV strains have been shown to productively infect, in addition to murine cells, various heterologous cell lines including those of human origin, albeit less efficiently than murine cells. Furthermore, there have been reports that the continued passage of MMTV in heterologous cell lines gives rise to novel variants that are able to infect naive non-murine cells with higher efficiency than the parental virus. RESULTS: We show that MMTV(C3H), like other MMTV strains, that had undergone a number of replication cycles in non-murine cells displayed an increased replication kinetic, as compared to parental virus, when applied on naive human cells. Sequence analysis of several replication kinetic variants and the parental virus, together with calculation of the ratio of non-synonymous to synonymous mutations at individual codons, revealed that several regions within the viral genome were under strong positive selection pressure during viral replication in human cells. The mutation responsible, at least in part, for the phenotypic change was subsequently mapped to the segment of env encoding the receptor binding site (F(40)HGFR(44)). Introduction of the identified mutation, leading to single amino acid substitution (G42E), into egfp-containing recombinant MMTV virions enhanced their ability to bind to and infect human cells. Interestingly, neither the replication kinetic mutant nor the parental virus required human TfR1 for infection. Knock-out of TFR1 gene from the human genome did not decrease the susceptibility of Hs578T cells to virus infection. Furthermore, the expression of human TfR1, in contrast to mouse TfR1, did not enhance the susceptibility of MMTV-resistant Chinese hamster ovary cells. Thus, human TfR1 is dispensable for infection and another cell surface molecule mediates the MMTV entry into human cells. CONCLUSION: Taken together, our data explain the mechanism enabling MMTV to form ‘host-range variants’ in non-murine cells that has been known for a long time, the basis of which remained obscure. Our findings may expand our understanding of how viruses gain capability to cross species-specific barriers to infect new hosts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-015-0168-2) contains supplementary material, which is available to authorized users.",2015 May 16,"['Konstantoulas, Constantine James', 'Lamp, Benjamin', 'Rumenapf, Tillman Hans', 'Indik, Stanislav']",Retrovirology,,,True
f223f427cbdd077ec84931fad74fb3a7a46fbc67,PMC,Recent Advances in Dipeptidyl-Peptidase-4 Inhibition Therapy: Lessons from the Bench and Clinical Trials,http://dx.doi.org/10.1155/2015/606031,PMC4446505,26075284,CC BY,"DPP4 inhibitors (DPP4i) are a class of newly developed antidiabetic drugs which preserve incretin hormones and promote postprandial insulin secretion. Although the cardiovascular effect of DPP4 inhibition has been substantially studied, the exact role of DPP4 in cardiovascular disease especially in humans remains elusive. Previous small studies and meta-analyses have suggested a benefit in both surrogate outcomes and cardiovascular events for these agents. However, there was growing evidence in recent years questioning the cardioprotective effect of DPP4i. Further, a signal of heart failure hospitalization in a recent large scale clinical trial SAVOR-TIMI 53 has called into question the safety of these agents and their utility in the treatment of cardiovascular disease. In this review, we will revisit the physiologic function of DPP4 and discuss its role in cardiometabolic disease based on recent experimental and clinical studies.",2015 May 14,"['Zhong, Jixin', 'Gong, Quan', 'Goud, Aditya', 'Srinivasamaharaj, Srividya', 'Rajagopalan, Sanjay']",J Diabetes Res,,,True
293e8a49b5c0ee33d5e1098b3f4ca9b613c516fd,PMC,Homology-Independent Metrics for Comparative Genomics,http://dx.doi.org/10.1016/j.csbj.2015.04.005,PMC4446528,26029354,CC BY,"A mainstream procedure to analyze the wealth of genomic data available nowadays is the detection of homologous regions shared across genomes, followed by the extraction of biological information from the patterns of conservation and variation observed in such regions. Although of pivotal importance, comparative genomic procedures that rely on homology inference are obviously not applicable if no homologous regions are detectable. This fact excludes a considerable portion of “genomic dark matter” with no significant similarity — and, consequently, no inferred homology to any other known sequence — from several downstream comparative genomic methods. In this review we compile several sequence metrics that do not rely on homology inference and can be used to compare nucleotide sequences and extract biologically meaningful information from them. These metrics comprise several compositional parameters calculated from sequence data alone, such as GC content, dinucleotide odds ratio, and several codon bias metrics. They also share other interesting properties, such as pervasiveness (patterns persist on smaller scales) and phylogenetic signal. We also cite examples where these homology-independent metrics have been successfully applied to support several bioinformatics challenges, such as taxonomic classification of biological sequences without homology inference. They where also used to detect higher-order patterns of interactions in biological systems, ranging from detecting coevolutionary trends between the genomes of viruses and their hosts to characterization of gene pools of entire microbial communities. We argue that, if correctly understood and applied, homology-independent metrics can add important layers of biological information in comparative genomic studies without prior homology inference.",2015 May 4,"['Coutinho, Tarcisio José Domingos', 'Franco, Glória Regina', 'Lobo, Francisco Pereira']",Comput Struct Biotechnol J,,,False
9223fd6478822761845291fe2ac429ca6ddbb45a,PMC,Association of targeted multiplex PCR with resequencing microarray for the detection of multiple respiratory pathogens,http://dx.doi.org/10.3389/fmicb.2015.00532,PMC4446546,26074910,CC BY,"A large number of viral and bacterial organisms are responsible for community-acquired pneumonia (CAP) which contributes to substantial burden on health management. A new resequencing microarray (RPM-IVDC1) associated with targeted multiplex PCR was recently developed and validated for multiple respiratory viruses detection and discrimination. In this study, we evaluated the capability of RPM-IVDC1 for simultaneous identification of multiple viral and bacterial organisms. The nasopharyngeal aspirates (NPAs) of 110 consecutive CAP patients, aged from 1 month to 96 years old, were collected from five distinct general hospitals in Beijing during 1-year period. The samples were subjected to the RPM-IVDC1 established protocol as compared to a real-time PCR (qRT-PCR), which was used as standard. The results of virus detection were consistent with those previously described. A total of 37 of Streptococcus pneumoniae, 14 of Haemophilus influenzae, 10 of Mycoplasma pneumoniae, two of Klebsiella pneumoniae and one of Moraxella catarrhalis were detected by RPM-IVDC1. The sensitivities and specificities were compared with those of qRT-PCR for S. pneumoniae (100, 100%, respectively), H. influenzae (92.3, 97.9%, respectively), M. pneumoniae (69.2, 99.0%, respectively), K. pneumoniae (100, 100%, respectively), and M. catarrhalis (100, 100%, respectively). Additional 22 of Streptococcus spp., 24 of Haemophilus spp. and 16 of Neisseria spp. were identified. In addition, methicillin-resistant and carbapenemases allele were also found in nine of Staphylococcus spp. and one of K. pneumoniae, respectively. These results demonstrated the capability of RPM-IVDC1 for simultaneous detection of broad-spectrum respiratory pathogens in complex backgrounds and the advantage of accessing to the actual sequences, showing great potential use of epidemic outbreak investigation. The detection results should be carefully interpreted when introducing this technique in the clinical diagnostics.",2015 May 28,"['Shen, Hongwei', 'Zhu, Bingqing', 'Wang, Shulian', 'Mo, Haolian', 'Wang, Ji', 'Li, Jin', 'Zhang, Chen', 'Zeng, Huashu', 'Guan, Li', 'Shi, Weixian', 'Zhang, Yong', 'Ma, Xuejun']",Front Microbiol,,,True
bbe42ce008a9dd9e25c03c36113d763dba358cbb,PMC,Phosphatidic Acid Produced by Phospholipase D Promotes RNA Replication of a Plant RNA Virus,http://dx.doi.org/10.1371/journal.ppat.1004909,PMC4447390,26020241,CC BY,"Eukaryotic positive-strand RNA [(+)RNA] viruses are intracellular obligate parasites replicate using the membrane-bound replicase complexes that contain multiple viral and host components. To replicate, (+)RNA viruses exploit host resources and modify host metabolism and membrane organization. Phospholipase D (PLD) is a phosphatidylcholine- and phosphatidylethanolamine-hydrolyzing enzyme that catalyzes the production of phosphatidic acid (PA), a lipid second messenger that modulates diverse intracellular signaling in various organisms. PA is normally present in small amounts (less than 1% of total phospholipids), but rapidly and transiently accumulates in lipid bilayers in response to different environmental cues such as biotic and abiotic stresses in plants. However, the precise functions of PLD and PA remain unknown. Here, we report the roles of PLD and PA in genomic RNA replication of a plant (+)RNA virus, Red clover necrotic mosaic virus (RCNMV). We found that RCNMV RNA replication complexes formed in Nicotiana benthamiana contained PLDα and PLDβ. Gene-silencing and pharmacological inhibition approaches showed that PLDs and PLDs-derived PA are required for viral RNA replication. Consistent with this, exogenous application of PA enhanced viral RNA replication in plant cells and plant-derived cell-free extracts. We also found that a viral auxiliary replication protein bound to PA in vitro, and that the amount of PA increased in RCNMV-infected plant leaves. Together, our findings suggest that RCNMV hijacks host PA-producing enzymes to replicate.",2015 May 28,"['Hyodo, Kiwamu', 'Taniguchi, Takako', 'Manabe, Yuki', 'Kaido, Masanori', 'Mise, Kazuyuki', 'Sugawara, Tatsuya', 'Taniguchi, Hisaaki', 'Okuno, Tetsuro']",PLoS Pathog,,,True
1196301d4e04f2283f18f95fbbbd6bc5cf6e341f,PMC,The Use of Nanotrap Particles in the Enhanced Detection of Rift Valley Fever Virus Nucleoprotein,http://dx.doi.org/10.1371/journal.pone.0128215,PMC4447397,26020252,CC BY,"BACKGROUND: Rift Valley fever virus (RVFV) is a highly pathogenic arthropod-borne virus that has a detrimental effect on both livestock and human populations. While there are several diagnostic methodologies available for RVFV detection, many are not sensitive enough to diagnose early infections. Furthermore, detection may be hindered by high abundant proteins such as albumin. Previous findings have shown that Nanotrap particles can be used to significantly enhance detection of various small analytes of low abundance. We have expanded upon this repertoire to show that this simple and efficient sample preparation technology can drastically improve the detection of the RVFV nucleoprotein (NP), the most abundant and widely used viral protein for RVFV diagnostics. RESULTS: After screening multiple Nanotrap particle architectures, we found that one particle, NT45, was optimal for RVFV NP capture, as demonstrated by western blotting. NT45 significantly enhanced detection of the NP at levels undetectable without the technology. Importantly, we demonstrated that Nanotrap particles are capable of concentrating NP in a number of matrices, including infected cell lysates, viral supernatants, and animal sera. Specifically, NT45 enhanced detection of NP at various viral titers, multiplicity of infections, and time points. Our most dramatic results were observed in spiked serum samples, where high abundance serum proteins hindered detection of NP without Nanotrap particles. Nanotrap particles allowed for sample cleanup and subsequent detection of RVFV NP. Finally, we demonstrated that incubation of our samples with Nanotrap particles protects the NP from degradation over extended periods of time (up to 120 hours) and at elevated temperatures (at 37ºC). CONCLUSION: This study demonstrates that Nanotrap particles are capable of drastically lowering the limit of detection for RVFV NP by capturing, concentrating, and preserving RVFV NP in clinically relevant matrices. These studies can be extended to a wide range of pathogens and their analytes of diagnostic interest.",2015 May 28,"['Shafagati, Nazly', 'Lundberg, Lindsay', 'Baer, Alan', 'Patanarut, Alexis', 'Fite, Katherine', 'Lepene, Benjamin', 'Kehn-Hall, Kylene']",PLoS One,,,True
6e25ab9800baa443a7f103bd9e4940cac7db05f6,PMC,Aspects of the Health Inspection Authority in the People’s Republic of China,http://dx.doi.org/10.1186/s12889-015-1832-0,PMC4449968,25989798,CC BY,"BACKGROUND: In China, there was a pressing need to establish a governmental agency to oversee the organizations that provide public health and medical services. The Chinese Health Inspection Authority (HIA), a relatively independent organization functioning at each administrative level (provincial, municipal, and county), was mandated to conduct 11 health inspection functions to maintain efficient public health and medical services. These functions include issuing health permit, conducting health supervision and inspection, health testing and evaluation, case investigation, complaint handling, managing public health crisis, monitoring and safeguarding public health at major public events, enforcing supervision and inspection compliance, public health education, information management, and team training and management. Since the reform of the health inspection system by the Ministry of Health in 2000, the HIA underwent a series of changes and transitions. This study aimed to describe and assess the five factors that were considered to be important for meeting service delivery objectives of the HIA in the People’s Republic of China. METHODS: A total of 604 HIAs, sampled across three geographical regions of China at three administrative levels, participated in a cross-sectional survey conducted in 2013. Descriptive statistics were used to analyze the status of mandated operations, manpower, revenue and expenditures, and institutional infrastructure. Differences in these characteristics across the geographical regions and administrative levels were compared. RESULTS: On average, the HIAs had not fully implemented the 11 mandated functions at any administrative levels. Governmental financial allocations were the main sources of revenue. Three primary personnel employment models coexisted and most employed the quasi-civil service employment model. The institutional infrastructure did not meet governmental mandated standards with respect to building area or the number and types of equipment available to conduct key functions. CONCLUSIONS: In 2012, the majority of the HIAs in China at the provincial, municipal, and county levels did not meet the mandated requirements, although positive indications toward meeting these requirements were observed. It is necessary for the government to pay more attention to institutional resources (buildings, equipment, and the level of the staff’s educational attainment) and ensure that the HIAs can meet their service delivery objectives.",2015 May 20,"['Ma, Sha', 'Chen, Gang', 'Tan, B-K']",BMC Public Health,,,True
c5c188fe8bbf7f71f4f6f96dc52747deac68ee3f,PMC,The Serum Profile of Hypercytokinemia Factors Identified in H7N9-Infected Patients can Predict Fatal Outcomes,http://dx.doi.org/10.1038/srep10942,PMC4450576,26028236,CC BY,"The novel avian origin influenza A (H7N9) virus has caused severe diseases in humans in eastern China since the spring of 2013. Fatal outcomes of H7N9 infections are often attributed to the severe pneumonia and acute respiratory distress syndrome (ARDS). There is urgent need to discover biomarkers predicting the progression of disease and fatal outcome of potentially lethal flu infections, based on sound statistical analysis. We discovered that 34 of the 48 cytokines and chemokines examined in this study were significantly elevated in the plasma samples from patients infected with H7N9. We report for the first time that the levels of MIF, SCF, MCP-1, HGF, and SCGF-β are highly positively linked to disease severity and the profile of mediators MIF, SCF, MCP-1, HGF, SCGF-β, IP-10, IL-18, and IFN-γ is an independent outcome predictor.",2015 Jun 1,"['Guo, Jing', 'Huang, Fengming', 'Liu, Jun', 'Chen, Yu', 'Wang, Wei', 'Cao, Bin', 'Zou, Zhen', 'Liu, Song', 'Pan, Jingcao', 'Bao, Changjun', 'Zeng, Mei', 'Xiao, Haixia', 'Gao, Hainv', 'Yang, Shigui', 'Zhao, Yan', 'Liu, Qiang', 'Zhou, Huandi', 'Zhu, Jingdong', 'Liu, Xiaoli', 'Liang, Weifeng', 'Yang, Yida', 'Zheng, Shufa', 'Yang, Jiezuan', 'Diao, Hongyan', 'Su, Kunkai', 'Shao, Li', 'Cao, Hongcui', 'Wu, Ying', 'Zhao, Min', 'Tan, Shuguang', 'Li, Hui', 'Xu, Xiaoqing', 'Wang, Chunmei', 'Zhang, Jianmin', 'Wang, Li', 'Wang, Jianwei', 'Xu, Jun', 'Li, Dangsheng', 'Zhong, Nanshan', 'Cao, Xuetao', 'Gao, George F.', 'Li, Lanjuan', 'Jiang, Chengyu']",Sci Rep,,,True
f72f1b06430dd304beddfb96b80d4a20aa8f3d23,PMC,The Serum Profile of Hypercytokinemia Factors Identified in H7N9-Infected Patients can Predict Fatal Outcomes,http://dx.doi.org/10.1038/srep10942,PMC4450576,26028236,CC BY,"The novel avian origin influenza A (H7N9) virus has caused severe diseases in humans in eastern China since the spring of 2013. Fatal outcomes of H7N9 infections are often attributed to the severe pneumonia and acute respiratory distress syndrome (ARDS). There is urgent need to discover biomarkers predicting the progression of disease and fatal outcome of potentially lethal flu infections, based on sound statistical analysis. We discovered that 34 of the 48 cytokines and chemokines examined in this study were significantly elevated in the plasma samples from patients infected with H7N9. We report for the first time that the levels of MIF, SCF, MCP-1, HGF, and SCGF-β are highly positively linked to disease severity and the profile of mediators MIF, SCF, MCP-1, HGF, SCGF-β, IP-10, IL-18, and IFN-γ is an independent outcome predictor.",2015 Jun 1,"['Guo, Jing', 'Huang, Fengming', 'Liu, Jun', 'Chen, Yu', 'Wang, Wei', 'Cao, Bin', 'Zou, Zhen', 'Liu, Song', 'Pan, Jingcao', 'Bao, Changjun', 'Zeng, Mei', 'Xiao, Haixia', 'Gao, Hainv', 'Yang, Shigui', 'Zhao, Yan', 'Liu, Qiang', 'Zhou, Huandi', 'Zhu, Jingdong', 'Liu, Xiaoli', 'Liang, Weifeng', 'Yang, Yida', 'Zheng, Shufa', 'Yang, Jiezuan', 'Diao, Hongyan', 'Su, Kunkai', 'Shao, Li', 'Cao, Hongcui', 'Wu, Ying', 'Zhao, Min', 'Tan, Shuguang', 'Li, Hui', 'Xu, Xiaoqing', 'Wang, Chunmei', 'Zhang, Jianmin', 'Wang, Li', 'Wang, Jianwei', 'Xu, Jun', 'Li, Dangsheng', 'Zhong, Nanshan', 'Cao, Xuetao', 'Gao, George F.', 'Li, Lanjuan', 'Jiang, Chengyu']",Sci Rep,,,False
7458d605a0f34ffeeb3a2073c654f462ed1716e1,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.15.010615,PMC4450712,,CC BY,,2015 Jun 1,,Bull World Health Organ,,,False
135a7409bb3edb0dab450d94baa025e28fdaa586,PMC,Global funding for local health issues,http://dx.doi.org/10.2471/BLT.15.030615,PMC4450714,26240457,CC BY,Jeremy Farrar tells Fiona Fleck why global health research must go local to respond to social needs.,2015 Jun 1,,Bull World Health Organ,,,False
e546530d3c2507a91afb8ed59c87cac0c8b501da,PMC,Nucleocytoplasmic transport of nucleocapsid proteins of enveloped RNA viruses,http://dx.doi.org/10.3389/fmicb.2015.00553,PMC4451415,26082769,CC BY,"Most viruses with non-segmented single stranded RNA genomes complete their life cycle in the cytoplasm of infected cells. However, despite undergoing replication in the cytoplasm, the structural proteins of some of these RNA viruses localize to the nucleus at specific times in the virus life cycle, primarily early in infection. Limited evidence suggests that this enhances successful viral replication by interfering with or inhibiting the host antiviral response. Nucleocapsid proteins of RNA viruses have a well-established, essential cytoplasmic role in virus replication and assembly. Intriguingly, nucleocapsid proteins of some RNA viruses also localize to the nucleus/nucleolus of infected cells. Their nuclear function is less well understood although significant advances have been made in recent years. This review will focus on the nucleocapsid protein of cytoplasmic enveloped RNA viruses, including their localization to the nucleus/nucleolus and function therein. A greater understanding of the nuclear localization of nucleocapsid proteins has the potential to enhance therapeutic strategies as it can be a target for the development of live-attenuated vaccines or antiviral drugs.",2015 Jun 2,"['Wulan, Wahyu N.', 'Heydet, Deborah', 'Walker, Erin J.', 'Gahan, Michelle E.', 'Ghildyal, Reena']",Front Microbiol,,,True
2b244041ab6f2ab167b76c5b17332c5598b56431,PMC,Computational Docking Study of p7 Ion Channel from HCV Genotype 3 and Genotype 4 and Its Interaction with Natural Compounds,http://dx.doi.org/10.1371/journal.pone.0126510,PMC4451521,26030803,CC BY,"BACKGROUND: The current standard care therapy for hepatitis C virus (HCV) infection consists of two regimes, namely interferon-based and interferon-free treatments. The treatment through the combination of ribavirin and pegylated interferon is expensive, only mildly effective, and is associated with severe side effects. In 2011, two direct-acting antiviral (DAA) drugs, boceprevir and telaprevir, were licensed that have shown enhanced sustained virologic response (SVR) in phase III clinical trial, however, these interferon-free treatments are more sensitive to HCV genotype 1 infection. The variable nature of HCV, and the limited number of inhibitors developed thus aim in expanding the repertoire of available drug targets, resulting in targeting the virus assembly therapeutically. AIM: We conducted this study to predict the 3D structure of the p7 protein from the HCV genotypes 3 and 4. Approximately 63 amino acid residues encoded in HCV render this channel sensitive to inhibitors, making p7 a promising target for novel therapies. HCV p7 protein forms a small membrane known as viroporin, and is essential for effective self-assembly of large channels that conduct cation assembly and discharge infectious virion particles. METHOD: In this study, we screened drugs and flavonoids known to disrupt translation and production of HCV proteins, targeted against the active site of p7 residues of HCV genotype 3 (GT3) (isolatek3a) and HCV genotype 4a (GT4) (isolateED43). Furthermore, we conducted a quantitative structure–activity relationship and docking interaction study. RESULTS: The drug NB-DNJ formed the highest number of hydrogen bond interactions with both modeled p7 proteins with high interaction energy, followed by BIT225. A flavonoid screen demonstrated that Epigallocatechin gallate (EGCG), nobiletin, and quercetin, have more binding modes in GT3 than in GT4. Thus, the predicted p7 protein molecule of HCV from GT3 and GT4 provides a general avenue to target structure-based antiviral compounds. CONCLUSIONS: We hypothesize that the inhibitors of viral p7 identified in this screen may be a new class of potent agents, but further confirmation in vitro and in vivo is essential. This structure-guided drug design for both GT3 and GT4 can lead to the identification of drug-like natural compounds, confirming p7 as a new target in the rapidly increasing era of HCV.",2015 Jun 1,"['Mathew, Shilu', 'Fatima, Kaneez', 'Fatmi, M. Qaiser', 'Archunan, Govindaraju', 'Ilyas, Muhammad', 'Begum, Nargis', 'Azhar, Esam', 'Damanhouri, Ghazi', 'Qadri, Ishtiaq']",PLoS One,,,True
0b7d50ddfae18226d4a66c578d9235d872c85056,PMC,T(FH) cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1,http://dx.doi.org/10.1038/srep10443,PMC4451806,26034905,CC BY,"CD4(+) T follicular helper cells (T(FH)) in germinal centers are required for maturation of B-cells. While the role of T(FH)-cells has been studied in blood and lymph nodes of HIV-1 infected individuals, its role in the mucosal tissues has not been investigated. We show that the gut and female reproductive tract (FRT) of humanized DRAG mice have a high level of human lymphocytes and a high frequency of T(FH) (CXCR5(+)PD-1(++)) and precursor-T(FH) (CXCR5(+)PD-1(+)) cells. The majority of T(FH)-cells expressed CCR5 and CXCR3 and are the most permissive to HIV-1 infection. A single low-dose intravaginal HIV-1 challenge of humanized DRAG mice results in 100% infectivity with accumulation of T(FH)-cells mainly in the Peyer’s patches and FRT. The novel finding of T(FH)-cells in the FRT may contribute to the high susceptibility of DRAG mice to HIV-1 infection. This mouse model thus provides new opportunities to study T(FH)-cells and to evaluate HIV-1 vaccines.",2015 Jun 2,"['Allam, Atef', 'Majji, Sai', 'Peachman, Kristina', 'Jagodzinski, Linda', 'Kim, Jiae', 'Ratto-Kim, Silvia', 'Wijayalath, Wathsala', 'Merbah, Melanie', 'Kim, Jerome H.', 'Michael, Nelson L.', 'Alving, Carl R.', 'Casares, Sofia', 'Rao, Mangala']",Sci Rep,,,True
1ae6649a17c7eb7f14611bbabcf0cb0a60121d7c,PMC,T(FH) cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1,http://dx.doi.org/10.1038/srep10443,PMC4451806,26034905,CC BY,"CD4(+) T follicular helper cells (T(FH)) in germinal centers are required for maturation of B-cells. While the role of T(FH)-cells has been studied in blood and lymph nodes of HIV-1 infected individuals, its role in the mucosal tissues has not been investigated. We show that the gut and female reproductive tract (FRT) of humanized DRAG mice have a high level of human lymphocytes and a high frequency of T(FH) (CXCR5(+)PD-1(++)) and precursor-T(FH) (CXCR5(+)PD-1(+)) cells. The majority of T(FH)-cells expressed CCR5 and CXCR3 and are the most permissive to HIV-1 infection. A single low-dose intravaginal HIV-1 challenge of humanized DRAG mice results in 100% infectivity with accumulation of T(FH)-cells mainly in the Peyer’s patches and FRT. The novel finding of T(FH)-cells in the FRT may contribute to the high susceptibility of DRAG mice to HIV-1 infection. This mouse model thus provides new opportunities to study T(FH)-cells and to evaluate HIV-1 vaccines.",2015 Jun 2,"['Allam, Atef', 'Majji, Sai', 'Peachman, Kristina', 'Jagodzinski, Linda', 'Kim, Jiae', 'Ratto-Kim, Silvia', 'Wijayalath, Wathsala', 'Merbah, Melanie', 'Kim, Jerome H.', 'Michael, Nelson L.', 'Alving, Carl R.', 'Casares, Sofia', 'Rao, Mangala']",Sci Rep,,,False
7870870602f0a4edb3a7ea468659e2eb23cb2202,PMC,Protection against Amoebic Liver Abscess in Hamster by Intramuscular Immunization with an Autographa californica Baculovirus Driving the Expression of the Gal-Lectin LC3 Fragment,http://dx.doi.org/10.1155/2015/760598,PMC4452260,26090442,CC BY,"In a previous study, we demonstrated that oral immunization using Autographa californica baculovirus driving the expression of the Gal-lectin LC3 fragment (AcNPV-LC3) of Entamoeba histolytica conferred protection against ALA development in hamsters. In this study, we determined the ability of AcNPV-LC3 to protect against ALA by the intramuscular route as well as the liver immune response associated with protection. Results showed that 55% of hamsters IM immunized with AcNPV-LC3 showed sterile protection against ALA, whereas other 20% showed reduction in the size and extent of abscesses, resulting in some protection in 75% of animals compared to the sham control group. Levels of protection showed a linear correlation with the development and intensity of specific antiamoeba cellular and humoral responses, evaluated in serum and spleen of hamsters, respectively. Evaluation of the Th1/Th2 cytokine patterns expressed in the liver of hamsters showed that sterile protection was associated with the production of high levels of IFNγ and IL-4. These results suggest that the baculovirus system is equally efficient by the intramuscular as well as the oral routes for ALA protection and that the Gal-lectin LC3 fragment is a highly protective antigen against hepatic amoebiasis through the local induction of IFNγ and IL-4.",2015 May 19,"['Meneses-Ruiz, Dulce María', 'Aguilar-Diaz, Hugo', 'Bobes, Raúl José', 'Sampieri, Alicia', 'Vaca, Luis', 'Laclette, Juan Pedro', 'Carrero, Julio César']",Biomed Res Int,,,True
252e6f853b7025fa235432baf9869ae4f51a020d,PMC,Host Tissue and Glycan Binding Specificities of Avian Viral Attachment Proteins Using Novel Avian Tissue Microarrays,http://dx.doi.org/10.1371/journal.pone.0128893,PMC4452732,26035584,CC BY,"The initial interaction between viral attachment proteins and the host cell is a critical determinant for the susceptibility of a host for a particular virus. To increase our understanding of avian pathogens and the susceptibility of poultry species, we developed novel avian tissue microarrays (TMAs). Tissue binding profiles of avian viral attachment proteins were studied by performing histochemistry on multi-species TMA, comprising of selected tissues from ten avian species, and single-species TMAs, grouping organ systems of each species together. The attachment pattern of the hemagglutinin protein was in line with the reported tropism of influenza virus H5N1, confirming the validity of TMAs in profiling the initial virus-host interaction. The previously believed chicken-specific coronavirus (CoV) M41 spike (S1) protein displayed a broad attachment pattern to respiratory tissues of various avian species, albeit with lower affinity than hemagglutinin, suggesting that other avian species might be susceptible for chicken CoV. When comparing tissue-specific binding patterns of various avian coronaviral S1 proteins on the single-species TMAs, chicken and partridge CoV S1 had predominant affinity for the trachea, while pigeon CoV S1 showed marked preference for lung of their respective hosts. Binding of all coronaviral S1 proteins was dependent on sialic acids; however, while chicken CoV S1 preferred sialic acids type I lactosamine (Gal(1-3)GlcNAc) over type II (Gal(1-4)GlcNAc), the fine glycan specificities of pigeon and partridge CoVs were different, as chicken CoV S1-specific sialylglycopolymers could not block their binding to tissues. Taken together, TMAs provide a novel platform in the field of infectious diseases to allow identification of binding specificities of viral attachment proteins and are helpful to gain insight into the susceptibility of host and organ for avian pathogens.",2015 Jun 2,"['Ambepitiya Wickramasinghe, Iresha N.', 'de Vries, Robert P.', 'Eggert, Amber M.', 'Wandee, Nantaporn', 'de Haan, Cornelis A. M.', 'Gröne, Andrea', 'Verheije, Monique H.']",PLoS One,,,True
118373b29085c6212547a34993be16eb98008dd0,PMC,Host Tissue and Glycan Binding Specificities of Avian Viral Attachment Proteins Using Novel Avian Tissue Microarrays,http://dx.doi.org/10.1371/journal.pone.0128893,PMC4452732,26035584,CC BY,"The initial interaction between viral attachment proteins and the host cell is a critical determinant for the susceptibility of a host for a particular virus. To increase our understanding of avian pathogens and the susceptibility of poultry species, we developed novel avian tissue microarrays (TMAs). Tissue binding profiles of avian viral attachment proteins were studied by performing histochemistry on multi-species TMA, comprising of selected tissues from ten avian species, and single-species TMAs, grouping organ systems of each species together. The attachment pattern of the hemagglutinin protein was in line with the reported tropism of influenza virus H5N1, confirming the validity of TMAs in profiling the initial virus-host interaction. The previously believed chicken-specific coronavirus (CoV) M41 spike (S1) protein displayed a broad attachment pattern to respiratory tissues of various avian species, albeit with lower affinity than hemagglutinin, suggesting that other avian species might be susceptible for chicken CoV. When comparing tissue-specific binding patterns of various avian coronaviral S1 proteins on the single-species TMAs, chicken and partridge CoV S1 had predominant affinity for the trachea, while pigeon CoV S1 showed marked preference for lung of their respective hosts. Binding of all coronaviral S1 proteins was dependent on sialic acids; however, while chicken CoV S1 preferred sialic acids type I lactosamine (Gal(1-3)GlcNAc) over type II (Gal(1-4)GlcNAc), the fine glycan specificities of pigeon and partridge CoVs were different, as chicken CoV S1-specific sialylglycopolymers could not block their binding to tissues. Taken together, TMAs provide a novel platform in the field of infectious diseases to allow identification of binding specificities of viral attachment proteins and are helpful to gain insight into the susceptibility of host and organ for avian pathogens.",2015 Jun 2,"['Ambepitiya Wickramasinghe, Iresha N.', 'de Vries, Robert P.', 'Eggert, Amber M.', 'Wandee, Nantaporn', 'de Haan, Cornelis A. M.', 'Gröne, Andrea', 'Verheije, Monique H.']",PLoS One,,,True
dd4a3353ae21a249a81f30e23fc416a1d948887b,PMC,Interaction between the Natural Components in Danhong Injection (DHI) with Serum Albumin (SA) and the Influence of the Coexisting Multi-Components on the SaB-BSA Binding System: Fluorescence and Molecular Docking Studies,http://dx.doi.org/10.1371/journal.pone.0128919,PMC4452768,26035712,CC BY,"Danhong injection (DHI) is a widely used Chinese Materia Medica standardized product for the clinical treatment of ischemic encephalopathy and coronary heart disease. The bindings of eight natural components in DHI between bovine serum albumin (BSA) were studied by fluorescence spectroscopy technology and molecular docking. According to the results, the quenching process of salvianolic acid B and hydroxysafflor yellow A was a static quenching procedure through the analysis of quenching data by the Stern-Volmer equation, the modified Stern-Volmer equation, and the modified Scatchard equation. Meanwhile, syringin (Syr) enhanced the fluorescence of BSA, and the data were analyzed using the Lineweaver-Burk equation. Molecular docking suggested that all of these natural components bind to serum albumin at the site I location. Further competitive experiments of SaB confirmed the result of molecular docking studies duo to the displacement of warfarin by SaB. Base on these studies, we selected SaB as a research target because it presented the strongest binding ability to BSA and investigated the influence of the multi-components coexisting in DHI on the interaction between the components of the SaB-BSA binding system. The participation of these natural components in DHI affected the interaction between the components of the SaB-BSA system. Therefore, when DHI is used in mammals, SaB is released from serum albumin more quickly than it is used alone. This work would provide a new experiment basis for revealing the scientific principle of compatibility for Traditional Chinese Medicine.",2015 Jun 2,"['Hao, Jia', 'Zhang, Yingyue', 'Wang, Xingrui', 'Yan, Huo', 'Liu, Erwei', 'Gao, Xiumei']",PLoS One,,,True
11f8eeb589bf8737b2805b3bb50ca12b73884c64,PMC,Identification of Putative ORF5 Protein of Porcine Circovirus Type 2 and Functional Analysis of GFP-Fused ORF5 Protein,http://dx.doi.org/10.1371/journal.pone.0127859,PMC4452787,26035722,CC BY,"Porcine circovirus type 2 (PCV2) is the essential infectious agent responsible for causing porcine circovirus-associated diseases in pigs. To date, eleven RNAs and five viral proteins of PCV2 have been detected. Here, we identified a novel viral gene within the PCV2 genome, termed ORF5, that exists at both the transcriptional and translational level during productive infection of PCV2 in porcine alveolar macrophages 3D4/2 (PAMs). Northern blot analysis was used to demonstrate that the ORF5 gene measures 180 bp in length and overlaps completely with ORF1 when read in the same direction. Site-directed mutagenesis was used to show that the ORF5 protein is not essential for PCV2 replication. To investigate the biological functions of the novel protein, we constructed a recombinant eukaryotic expression plasmid capable of expressing PCV2 ORF5. The results show that the GFP-tagged PCV2 ORF5 protein localizes to the endoplasmic reticulum (ER), is degraded via the proteasome, inhibits PAM growth and prolongs the S-phase of the cell cycle. Further studies show that the GFP-tagged PCV2 ORF5 protein induces ER stress and activates NF-κB, which was further confirmed by a significant upregulation in IL-6, IL-8 and COX-2 expression. In addition, five cellular proteins (GPNMB, CYP1A1, YWHAB, ZNF511 and SRSF3) were found to interact with ORF5 via yeast two-hybrid assay. These findings provide novel information on the identification and functional analysis of the PCV2 ORF5 protein and are likely to be of benefit in elucidating the molecular mechanisms of PCV2 pathogenicity. However, additional experiments are needed to validate the expression and function of the ORF5 protein during PCV2 infection in vitro before any definitive conclusion can be drawn.",2015 Jun 2,"['Lv, Qizhuang', 'Guo, Kangkang', 'Xu, Han', 'Wang, Tao', 'Zhang, Yanming']",PLoS One,,,True
616eb9a60a8da572b0a60b6d33f4618c91c7b55c,PMC,Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s) Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes,http://dx.doi.org/10.3390/v7052358,PMC4452910,26008694,CC BY,"Human coronavirus OC43 (HCoV-OC43) is one of five currently circulating human coronaviruses responsible for respiratory infections. Like all coronaviruses, it is characterized by its genome’s high plasticity. The objectives of the current study were to detect genetically distinct genotypes and eventually recombinant genotypes in samples collected in Lower Normandy between 2001 and 2013. To this end, we sequenced complete nsp12, S, and N genes of 15 molecular isolates of HCoV-OC43 from clinical samples and compared them to available data from the USA, Belgium, and Hong-Kong. A new cluster E was invariably detected from nsp12, S, and N data while the analysis of nsp12 and N genes revealed the existence of new F and G clusters respectively. The association of these different clusters of genes in our specimens led to the description of thirteen genetically distinct genotypes, among which eight recombinant viruses were discovered. Identification of these recombinant viruses, together with temporal analysis and tMRCA estimation, provides important information for understanding the dynamics of the evolution of these epidemic coronaviruses.",2015 May 7,"['Kin, Nathalie', 'Miszczak, Fabien', 'Lin, Wei', 'Ar Gouilh, Meriadeg', 'Vabret, Astrid', None]",Viruses,,,True
bb11206963e831f1652775d26e3e5e48634a4545,PMC,The Use of Convalescent Sera in Immune-Electron Microscopy to Detect Non-Suspected/New Viral Agents,http://dx.doi.org/10.3390/v7052683,PMC4452926,26008707,CC BY,"Negative staining electron microscopy methods can be employed for the diagnosis of viral particles in animal samples. In fact, negative staining electron microscopy methods are used to identify viruses, especially in minor species and wild animals, when no other methods are available and in cases of rare, emerging or re-emerging infections. In particular, immune-electron-microscopy with convalescent sera is employed to detect etiological agents when there are undiagnosed clinical outbreaks, when alternative diagnostic methods fail due to the lack of immunological reagents and primers, and when there is no indicative clinical suspect. An overview of immune-electron-microscopy with convalescent sera’s use in the diagnosis of new and unsuspected viruses in animals of domestic and wild species is provided through the descriptions of the following four diagnostic veterinary cases: (I) enteric viruses of pigs: Porcine Rotavirus, Porcine Epidemic Diarrhea Virus, Porcine Circovirus and Porcine Torovirus; (II) Rotavirus and astrovirus in young turkeys with enteritis; (III) Parvovirus-like particles in pheasants; and (IV) Lagoviruses: Rabbit Hemorrhagic Disease Virus and European Brown Hare Syndrome Virus.",2015 May 22,"['Lavazza, Antonio', 'Tittarelli, Cristiana', 'Cerioli, Monica']",Viruses,,,True
57f687e997bc7338adaefa13542e1f9ae7ddd7e6,PMC,Responding to the Pandemic of Falsified Medicines,http://dx.doi.org/10.4269/ajtmh.14-0393,PMC4455086,25897060,CC BY,"Over the past decade, the number of countries reporting falsified (fake, spurious/falsely labeled/counterfeit) medicines and the types and quantities of fraudulent drugs being distributed have increased greatly. The obstacles in combating falsified pharmaceuticals include 1) lack of consensus on definitions, 2) paucity of reliable and scalable technology to detect fakes before they reach patients, 3) poor global and national leadership and accountability systems for combating this scourge, and 4) deficient manufacturing and regulatory challenges, especially in China and India where fake products often originate. The major needs to improve the quality of the world's medicines fall into three main areas: 1) research to develop and compare accurate and affordable tools to identify high-quality drugs at all levels of distribution; 2) an international convention and national legislation to facilitate production and utilization of high-quality drugs and protect all countries from the criminal and the negligent who make, distribute, and sell life-threatening products; and 3) a highly qualified, well-supported international science and public health organization that will establish standards, drug-quality surveillance, and training programs like the U.S. Food and Drug Administration. Such leadership would give authoritative guidance for countries in cooperation with national medical regulatory agencies, pharmaceutical companies, and international agencies, all of which have an urgent interest and investment in ensuring that patients throughout the world have access to good quality medicines. The organization would also advocate strongly for including targets for achieving good quality medicines in the United Nations Millennium Development Goals and Sustainable Development Goals.",2015 Jun 3,"['Nayyar, Gaurvika M. L.', 'Attaran, Amir', 'Clark, John P.', 'Culzoni, M. Julia', 'Fernandez, Facundo M.', 'Herrington, James E.', 'Kendall, Megan', 'Newton, Paul N.', 'Breman, Joel G.']",Am J Trop Med Hyg,,,True
fc5e4a2de7d202adad95ea3fe26625bdebe817cf,PMC,Facilitated Tau Degradation by USP14 Aptamers via Enhanced Proteasome Activity,http://dx.doi.org/10.1038/srep10757,PMC4455164,26041011,CC BY,"The ubiquitin-proteasome system (UPS) is the primary mechanism by which intracellular proteins, transcription factors, and many proteotoxic proteins with aggregation-prone structures are degraded. The UPS is reportedly downregulated in various neurodegenerative disorders, with increased proteasome activity shown to be beneficial in many related disease models. Proteasomes function under tonic inhibitory conditions, possibly via the ubiquitin chain-trimming function of USP14, a proteasome-associated deubiquitinating enzyme (DUB). We identified three specific RNA aptamers of USP14 (USP14-1, USP14-2, and USP14-3) that inhibited its deubiquitinating activity. The nucleotide sequences of these non-cytotoxic USP14 aptamers contained conserved GGAGG motifs, with G-rich regions upstream, and similar secondary structures. They efficiently elevated proteasomal activity, as determined by the increased degradation of small fluorogenic peptide substrates and physiological polyubiquitinated Sic1 proteins. Additionally, proteasomal degradation of tau proteins was facilitated in the presence of the UPS14 aptamers in vitro. Our results indicate that these novel inhibitory UPS14 aptamers can be used to enhance proteasome activity, and to facilitate the degradation of proteotoxic proteins, thereby protecting cells from various neurodegenerative stressors.",2015 Jun 4,"['Lee, Jung Hoon', 'Shin, Seung Kyun', 'Jiang, Yanxialei', 'Choi, Won Hoon', 'Hong, Chaesun', 'Kim, Dong-Eun', 'Lee, Min Jae']",Sci Rep,,,True
d77a804e5bfdfe18f1f70345b2931ab2cb7eec17,PMC,Facilitated Tau Degradation by USP14 Aptamers via Enhanced Proteasome Activity,http://dx.doi.org/10.1038/srep10757,PMC4455164,26041011,CC BY,"The ubiquitin-proteasome system (UPS) is the primary mechanism by which intracellular proteins, transcription factors, and many proteotoxic proteins with aggregation-prone structures are degraded. The UPS is reportedly downregulated in various neurodegenerative disorders, with increased proteasome activity shown to be beneficial in many related disease models. Proteasomes function under tonic inhibitory conditions, possibly via the ubiquitin chain-trimming function of USP14, a proteasome-associated deubiquitinating enzyme (DUB). We identified three specific RNA aptamers of USP14 (USP14-1, USP14-2, and USP14-3) that inhibited its deubiquitinating activity. The nucleotide sequences of these non-cytotoxic USP14 aptamers contained conserved GGAGG motifs, with G-rich regions upstream, and similar secondary structures. They efficiently elevated proteasomal activity, as determined by the increased degradation of small fluorogenic peptide substrates and physiological polyubiquitinated Sic1 proteins. Additionally, proteasomal degradation of tau proteins was facilitated in the presence of the UPS14 aptamers in vitro. Our results indicate that these novel inhibitory UPS14 aptamers can be used to enhance proteasome activity, and to facilitate the degradation of proteotoxic proteins, thereby protecting cells from various neurodegenerative stressors.",2015 Jun 4,"['Lee, Jung Hoon', 'Shin, Seung Kyun', 'Jiang, Yanxialei', 'Choi, Won Hoon', 'Hong, Chaesun', 'Kim, Dong-Eun', 'Lee, Min Jae']",Sci Rep,,,False
05916d82efe1f937ee48f09df4e5d7c6fede83d3,PMC,Pattern formation in multiplex networks,http://dx.doi.org/10.1038/srep10840,PMC4455352,26042606,CC BY,"The advances in understanding complex networks have generated increasing interest in dynamical processes occurring on them. Pattern formation in activator-inhibitor systems has been studied in networks, revealing differences from the classical continuous media. Here we study pattern formation in a new framework, namely multiplex networks. These are systems where activator and inhibitor species occupy separate nodes in different layers. Species react across layers but diffuse only within their own layer of distinct network topology. This multiplicity generates heterogeneous patterns with significant differences from those observed in single-layer networks. Remarkably, diffusion-induced instability can occur even if the two species have the same mobility rates; condition which can never destabilize single-layer networks. The instability condition is revealed using perturbation theory and expressed by a combination of degrees in the different layers. Our theory demonstrates that the existence of such topology-driven instabilities is generic in multiplex networks, providing a new mechanism of pattern formation.",2015 Jun 4,"['Kouvaris, Nikos E.', 'Hata, Shigefumi', 'Guilera, Albert Díaz-']",Sci Rep,,,True
60c4a22f7179cf74c681f6aca2c2bff78ba4f8bb,PMC,Pattern formation in multiplex networks,http://dx.doi.org/10.1038/srep10840,PMC4455352,26042606,CC BY,"The advances in understanding complex networks have generated increasing interest in dynamical processes occurring on them. Pattern formation in activator-inhibitor systems has been studied in networks, revealing differences from the classical continuous media. Here we study pattern formation in a new framework, namely multiplex networks. These are systems where activator and inhibitor species occupy separate nodes in different layers. Species react across layers but diffuse only within their own layer of distinct network topology. This multiplicity generates heterogeneous patterns with significant differences from those observed in single-layer networks. Remarkably, diffusion-induced instability can occur even if the two species have the same mobility rates; condition which can never destabilize single-layer networks. The instability condition is revealed using perturbation theory and expressed by a combination of degrees in the different layers. Our theory demonstrates that the existence of such topology-driven instabilities is generic in multiplex networks, providing a new mechanism of pattern formation.",2015 Jun 4,"['Kouvaris, Nikos E.', 'Hata, Shigefumi', 'Guilera, Albert Díaz-']",Sci Rep,,,False
207bf71776ac6427c03a4dffa991148bb6dd4833,PMC,Epidemic predictions in an imperfect world: modelling disease spread with partial data,http://dx.doi.org/10.1098/rspb.2015.0205,PMC4455802,25948687,CC BY,"‘Big-data’ epidemic models are being increasingly used to influence government policy to help with control and eradication of infectious diseases. In the case of livestock, detailed movement records have been used to parametrize realistic transmission models. While livestock movement data are readily available in the UK and other countries in the EU, in many countries around the world, such detailed data are not available. By using a comprehensive database of the UK cattle trade network, we implement various sampling strategies to determine the quantity of network data required to give accurate epidemiological predictions. It is found that by targeting nodes with the highest number of movements, accurate predictions on the size and spatial spread of epidemics can be made. This work has implications for countries such as the USA, where access to data is limited, and developing countries that may lack the resources to collect a full dataset on livestock movements.",2015 Jun 7,"['Dawson, Peter M.', 'Werkman, Marleen', 'Brooks-Pollock, Ellen', 'Tildesley, Michael J.']",Proc Biol Sci,,,True
63a48c7eba8cc3c450016ba75dd52baf62ab0196,PMC,Epidemic predictions in an imperfect world: modelling disease spread with partial data,http://dx.doi.org/10.1098/rspb.2015.0205,PMC4455802,25948687,CC BY,"‘Big-data’ epidemic models are being increasingly used to influence government policy to help with control and eradication of infectious diseases. In the case of livestock, detailed movement records have been used to parametrize realistic transmission models. While livestock movement data are readily available in the UK and other countries in the EU, in many countries around the world, such detailed data are not available. By using a comprehensive database of the UK cattle trade network, we implement various sampling strategies to determine the quantity of network data required to give accurate epidemiological predictions. It is found that by targeting nodes with the highest number of movements, accurate predictions on the size and spatial spread of epidemics can be made. This work has implications for countries such as the USA, where access to data is limited, and developing countries that may lack the resources to collect a full dataset on livestock movements.",2015 Jun 7,"['Dawson, Peter M.', 'Werkman, Marleen', 'Brooks-Pollock, Ellen', 'Tildesley, Michael J.']",Proc Biol Sci,,,False
afd95cb874e0f82bbbdd467f64eaddd8fc904f86,PMC,Epidemic predictions in an imperfect world: modelling disease spread with partial data,http://dx.doi.org/10.1098/rspb.2015.0205,PMC4455802,25948687,CC BY,"‘Big-data’ epidemic models are being increasingly used to influence government policy to help with control and eradication of infectious diseases. In the case of livestock, detailed movement records have been used to parametrize realistic transmission models. While livestock movement data are readily available in the UK and other countries in the EU, in many countries around the world, such detailed data are not available. By using a comprehensive database of the UK cattle trade network, we implement various sampling strategies to determine the quantity of network data required to give accurate epidemiological predictions. It is found that by targeting nodes with the highest number of movements, accurate predictions on the size and spatial spread of epidemics can be made. This work has implications for countries such as the USA, where access to data is limited, and developing countries that may lack the resources to collect a full dataset on livestock movements.",2015 Jun 7,"['Dawson, Peter M.', 'Werkman, Marleen', 'Brooks-Pollock, Ellen', 'Tildesley, Michael J.']",Proc Biol Sci,,,False
66a137256be1759200f9fc27164e526287470c8e,PMC,Epidemic predictions in an imperfect world: modelling disease spread with partial data,http://dx.doi.org/10.1098/rspb.2015.0205,PMC4455802,25948687,CC BY,"‘Big-data’ epidemic models are being increasingly used to influence government policy to help with control and eradication of infectious diseases. In the case of livestock, detailed movement records have been used to parametrize realistic transmission models. While livestock movement data are readily available in the UK and other countries in the EU, in many countries around the world, such detailed data are not available. By using a comprehensive database of the UK cattle trade network, we implement various sampling strategies to determine the quantity of network data required to give accurate epidemiological predictions. It is found that by targeting nodes with the highest number of movements, accurate predictions on the size and spatial spread of epidemics can be made. This work has implications for countries such as the USA, where access to data is limited, and developing countries that may lack the resources to collect a full dataset on livestock movements.",2015 Jun 7,"['Dawson, Peter M.', 'Werkman, Marleen', 'Brooks-Pollock, Ellen', 'Tildesley, Michael J.']",Proc Biol Sci,,,True
57a926dfc15144fb103d05fd16a3b2cd9982d348,PMC,Epidemic predictions in an imperfect world: modelling disease spread with partial data,http://dx.doi.org/10.1098/rspb.2015.0205,PMC4455802,25948687,CC BY,"‘Big-data’ epidemic models are being increasingly used to influence government policy to help with control and eradication of infectious diseases. In the case of livestock, detailed movement records have been used to parametrize realistic transmission models. While livestock movement data are readily available in the UK and other countries in the EU, in many countries around the world, such detailed data are not available. By using a comprehensive database of the UK cattle trade network, we implement various sampling strategies to determine the quantity of network data required to give accurate epidemiological predictions. It is found that by targeting nodes with the highest number of movements, accurate predictions on the size and spatial spread of epidemics can be made. This work has implications for countries such as the USA, where access to data is limited, and developing countries that may lack the resources to collect a full dataset on livestock movements.",2015 Jun 7,"['Dawson, Peter M.', 'Werkman, Marleen', 'Brooks-Pollock, Ellen', 'Tildesley, Michael J.']",Proc Biol Sci,,,False
ce43f8f05a5db366babc9a6bfa086219534de208,PMC,HIV infection and antiretroviral therapy lead to unfolded protein response activation,http://dx.doi.org/10.1186/s12985-015-0298-0,PMC4455982,25976933,CC BY,"BACKGROUND: The unfolded protein response (UPR) is one of the pathways triggered to ensure quality control of the proteins assembled in the endoplasmic reticulum (ER) when cell homeostasis is compromised. This mechanism is primarily composed of three transmembrane proteins serving as stress sensors: PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 (IRE1). These three proteins’ synergic action elicits translation and transcriptional downstream pathways, leading to less protein production and activating genes that encode important proteins in folding processes, including chaperones. Previous reports showed that viruses have evolved mechanisms to curtail or customize this UPR signaling for their own benefit. However, HIV infection’s effect on the UPR has scarcely been investigated. METHODS: This work investigated UPR modulation by HIV infection by assessing UPR-related protein expression under in vitro and in vivo conditions via Western blotting. Antiretroviral (ARV) drugs’ influence on this stress response was also considered. RESULTS: In in vitro and in vivo analyses, our results confirm that HIV infection activates stress-response components and that ARV therapy contributes to changes in the UPR’s activation profile. CONCLUSIONS: This is the first report showing UPR-related protein expression in HIV target cells derived directly from HIV-infected patients receiving different ARV therapies. Thus, two mechanisms may occur simultaneously: interference by HIV itself and the ARV drugs’ pharmacological effects as UPR activators. New evidence of how HIV modulates the UPR to enhance its own replication and secure infection success is also presented. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0298-0) contains supplementary material, which is available to authorized users.",2015 May 15,"['Borsa, Mariana', 'Ferreira, Pedro L. C.', 'Petry, Andrea', 'Ferreira, Luiz G. E.', 'Camargo, Maristela M.', 'Bou-Habib, Dumith Chequer', 'Pinto, Aguinaldo R.']",Virol J,,,True
dcc14fe9ac1567bcde8412180b20c71162525235,PMC,Expected and Unexpected Features of the Newly Discovered Bat Influenza A-like Viruses,http://dx.doi.org/10.1371/journal.ppat.1004819,PMC4456350,26042416,CC BY,,2015 Jun 4,"['Ma, Wenjun', 'García-Sastre, Adolfo', 'Schwemmle, Martin']",PLoS Pathog,,,True
0bca841af11fa978a07f916ec43b34d7c88b71c1,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,True
15cf10fbb4513d95421f82b181f09720341d6891,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
12cd0a1920578e381e2a512f33c628492498696f,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
6dc8d7760c9abdca8c46e9637b7c0d69b817e1c3,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
54289fb6b35fe32c9e402d7dbfbf8919c22fcc09,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
accf201367ac6c6c64efe39b028fe9dff59fbed1,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
f1b2dd5bd5cff41a9309d5bf4e7d00339f0d2b51,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
4139177a6f98a38d4f1f572f8cd30bec0d39aaf2,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
b43fe5da2851b777800977b9cc3a497ef7bd0cd2,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
c2ef66ab7ee23556b8bd5ea61bffc3dcde4a153b,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
ca6f9746b47f8fe6e187a867ad37502d950a3fbd,PMC,Integrated cluster- and case-based surveillance for detecting stage III zoonotic pathogens: an example of Nipah virus surveillance in Bangladesh,http://dx.doi.org/10.1017/S0950268814002635,PMC4456770,25342551,CC BY,"This paper explores the utility of cluster- and case-based surveillance established in government hospitals in Bangladesh to detect Nipah virus, a stage III zoonotic pathogen. Physicians listed meningo-encephalitis cases in the 10 surveillance hospitals and identified a cluster when ⩾2 cases who lived within 30 min walking distance of one another developed symptoms within 3 weeks of each other. Physicians collected blood samples from the clustered cases. As part of case-based surveillance, blood was collected from all listed meningo-encephalitis cases in three hospitals during the Nipah season (January–March). An investigation team visited clustered cases’ communities to collect epidemiological information and blood from the living cases. We tested serum using Nipah-specific IgM ELISA. Up to September 2011, in 5887 listed cases, we identified 62 clusters comprising 176 encephalitis cases. We collected blood from 127 of these cases. In 10 clusters, we identified a total of 62 Nipah cases: 18 laboratory-confirmed and 34 probable. We identified person-to-person transmission of Nipah virus in four clusters. From case-based surveillance, we identified 23 (4%) Nipah cases. Faced with thousands of encephalitis cases, integrated cluster surveillance allows targeted deployment of investigative resources to detect outbreaks by stage III zoonotic pathogens in resource-limited settings.",2015 Jul 24,"['NASER, A. M.', 'HOSSAIN, M. J.', 'SAZZAD, H. M. S.', 'HOMAIRA, N.', 'GURLEY, E. S.', 'PODDER, G.', 'AFROJ, S.', 'BANU, S.', 'ROLLIN, P. E.', 'DASZAK, P.', 'AHMED, B.-N.', 'RAHMAN, M.', 'LUBY, S. P.']",Epidemiol Infect,,,True
138200f99f62c51776c9afec55d856e854ea8ff1,PMC,Alternative Antigen Processing for MHC Class I: Multiple Roads Lead to Rome,http://dx.doi.org/10.3389/fimmu.2015.00298,PMC4457021,26097483,CC BY,"The well described conventional antigen-processing pathway is accountable for most peptides that end up in MHC class I molecules at the cell surface. These peptides experienced liberation by the proteasome and transport by the peptide transporter TAP. However, there are multiple roads that lead to Rome, illustrated by the increasing number of alternative processing pathways that have been reported during last years. Interestingly, TAP-deficient individuals do not succumb to viral infections, suggesting that CD8 T cell immunity is sufficiently supported by alternative TAP-independent processing pathways. To date, a diversity of viral and endogenous TAP-independent peptides have been identified in the grooves of different MHC class I alleles. Some of these peptides are not displayed by normal TAP-positive cells and we therefore called them TEIPP, for “T-cell epitopes associated with impaired peptide processing.” TEIPPs are hidden self-antigens, are derived from normal housekeeping proteins, and are processed via unconventional processing pathways. Per definition, TEIPPs are presented via TAP-independent pathways, but recent data suggest that part of this repertoire still depend on proteasome and metalloprotease activity. An exception is the C-terminal peptide of the endoplasmic reticulum (ER)-membrane-spanning ceramide synthase Trh4 that is surprisingly liberated by the signal peptide peptidase (SPP), the proteolytic enzyme involved in cleaving leader sequences. The intramembrane cleaving SPP is thereby an important contributor of TAP-independent peptides. Its family members, like the Alzheimer’s related presenilins, might contribute as well, according to our preliminary data. Finally, alternative peptide routing is an emerging field and includes processes like the unfolded protein response, the ER-associated degradation, and autophagy-associated vesicular pathways. These data convince us that there is a world to be discovered in the field of unconventional antigen processing.",2015 Jun 5,"['Oliveira, Cláudia C.', 'van Hall, Thorbald']",Front Immunol,,,True
27ed601fcd2be1e67274e57dcc4ea6b01040e5ec,PMC,A Sweet Spot for Molecular Diagnostics: Coupling Isothermal Amplification and Strand Exchange Circuits to Glucometers,http://dx.doi.org/10.1038/srep11039,PMC4458886,26050646,CC BY,"Strand exchange nucleic acid circuitry can be used to transduce isothermal nucleic acid amplification products into signals that can be readable on an off-the-shelf glucometer. Loop-mediated isothermal amplification (LAMP) is limited by the accumulation of non-specific products, but nucleic acid circuitry can be used to probe and distinguish specific amplicons. By combining this high temperature isothermal amplification method with a thermostable invertase, we can directly transduce Middle-East respiratory syndrome coronavirus and Zaire Ebolavirus templates into glucose signals, with a sensitivity as low as 20–100 copies/μl, equating to atto-molar (or low zepto-mole). Virus from cell lysates and synthetic templates could be readily amplified and detected even in sputum or saliva. An OR gate that coordinately triggered on viral amplicons further guaranteed fail-safe virus detection. The method describes has potential for accelerating point-of-care applications, in that biological samples could be applied to a transducer that would then directly interface with an off-the-shelf, approved medical device.",2015 Jun 8,"['Du, Yan', 'Hughes, Randall A.', 'Bhadra, Sanchita', 'Jiang, Yu Sherry', 'Ellington, Andrew D.', 'Li, Bingling']",Sci Rep,,,True
ecef0f865903d77f2ffbe8cb1db275b7268ff77f,PMC,A Sweet Spot for Molecular Diagnostics: Coupling Isothermal Amplification and Strand Exchange Circuits to Glucometers,http://dx.doi.org/10.1038/srep11039,PMC4458886,26050646,CC BY,"Strand exchange nucleic acid circuitry can be used to transduce isothermal nucleic acid amplification products into signals that can be readable on an off-the-shelf glucometer. Loop-mediated isothermal amplification (LAMP) is limited by the accumulation of non-specific products, but nucleic acid circuitry can be used to probe and distinguish specific amplicons. By combining this high temperature isothermal amplification method with a thermostable invertase, we can directly transduce Middle-East respiratory syndrome coronavirus and Zaire Ebolavirus templates into glucose signals, with a sensitivity as low as 20–100 copies/μl, equating to atto-molar (or low zepto-mole). Virus from cell lysates and synthetic templates could be readily amplified and detected even in sputum or saliva. An OR gate that coordinately triggered on viral amplicons further guaranteed fail-safe virus detection. The method describes has potential for accelerating point-of-care applications, in that biological samples could be applied to a transducer that would then directly interface with an off-the-shelf, approved medical device.",2015 Jun 8,"['Du, Yan', 'Hughes, Randall A.', 'Bhadra, Sanchita', 'Jiang, Yu Sherry', 'Ellington, Andrew D.', 'Li, Bingling']",Sci Rep,,,True
95d3f266c79f401f0db216cf320eb2b28b5ed8b8,PMC,Effectiveness of non-pharmaceutical measures in preventing pediatric influenza: a case–control study,http://dx.doi.org/10.1186/s12889-015-1890-3,PMC4459072,26055522,CC BY,"BACKGROUND: Hygiene behavior plays a relevant role in infectious disease transmission. The aim of this study was to evaluate non-pharmaceutical interventions (NPI) in preventing pediatric influenza infections. METHODS: Laboratory confirmed influenza cases occurred during 2009–10 and 2010–11 seasons matched by age and date of consultation. NPI (frequency of hand washing, alcohol-based hand sanitizer use and hand washing after touching contaminated surfaces) during seven days prior to onset of symptoms were obtained from parents of cases and controls. RESULTS: Cases presented higher prevalence of underlying conditions such as pneumonia [OR = 3.23; 95 % CI: 1.38 – 7.58 p = 0.007], asthma [OR = 2.45; 95 % CI: 1.17 – 5.14 p = 0.02] and having more than 1 risk factor [OR = 1.67; 95 % CI: 0.99 – 2.82 p = 0.05]. Hand washing more than 5 times per day [aOR = 0.62; 95 % CI: 0.39 – 0.99 p = 0.04] was the only statistically significant protective factor. When considering two age groups (pre-school age 0–4 yrs and school age 5–17) yrs , only the school age group showed a negative association for influenza infection for both washing more than 5 times per day [aOR = 0.47; 95 % CI: 0.22 – 0.99 p = 0.04] and hand washing after touching contaminated surfaces [aOR = 0.19; 95 % CI: 0.04 – 0.86 p = 0.03]. CONCLUSION: Frequent hand washing should be recommended to prevent influenza infection in the community setting and in special in the school age group.",2015 Jun 9,"['Torner, Núria', 'Soldevila, Núria', 'Garcia, Juan Jose', 'Launes, Cristian', 'Godoy, Pere', 'Castilla, Jesús', 'Domínguez, Angela', None]",BMC Public Health,,,True
609c3b3465c19726b4777d17e3e2b19ca9de990b,PMC,Fecal virome analysis of three carnivores reveals a novel nodavirus and multiple gemycircularviruses,http://dx.doi.org/10.1186/s12985-015-0305-5,PMC4459443,25986582,CC BY,"BACKGROUND: More knowledge about viral populations in wild animals is needed in order to better understand and assess the risk of zoonotic diseases. In this study we performed viral metagenomic analysis of fecal samples from three healthy carnivores: a badger (Meles meles), a mongoose (Herpestes ichneumon) and an otter (Lutra lutra) from Portugal. RESULTS: We detected the presence of novel highly divergent viruses in the fecal material of the carnivores analyzed, such as five gemycircularviruses. Four of these gemycircularviruses were found in the mongoose and one in the badger. In addition we also identified an RNA-dependent RNA polymerase gene from a putative novel member of the Nodaviridae family in the fecal material of the otter. CONCLUSIONS: Together these results underline that many novel viruses are yet to be discovered and that fecal associated viruses are not always related to disease. Our study expands the knowledge of viral species present in the gut, although the interpretation of the true host species of such novel viruses needs to be reviewed with great caution.",2015 May 20,"['Conceição-Neto, Nádia', 'Zeller, Mark', 'Heylen, Elisabeth', 'Lefrère, Hanne', 'Mesquita, João Rodrigo', 'Matthijnssens, Jelle']",Virol J,,,True
af728043c4fdbde717229134e2cd8bada6760176,PMC,Development of a real-time reverse transcription loop-mediated isothermal amplification method for the rapid detection of porcine epidemic diarrhea virus,http://dx.doi.org/10.1186/s12985-015-0297-1,PMC4459462,25972083,CC BY,"BACKGROUND: Porcine epidemic diarrhea (PED) is an acute and highly contagious enteric disease characterized by severe enteritis, vomiting and watery diarrhea in swine. Recently, the outbreak of the epidemic disease has been a serious problem in swine industry. The objective of this study is to develop a rapid, sensitive, and real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for the detection of porcine epidemic diarrhea virus (PEDV) in less equipped laboratories. RESULTS: The optimal reaction condition of the current real-time RT-LAMP for PEDV was 62 °C for 45 min. It was capable of detecting PEDV from clinical samples and differentiating PEDV from several related porcine viruses, while it did not require additional expensive equipment. The minimum detection limit of the real-time RT-LAMP assay was 0.07PFU per reaction for PEDV RNA, making this assay approximately 100-fold more sensitive than that of one-step RT-PCR. By screening a panel of clinical specimens, the results showed that this method presented a similar sensitivity with real-time RT-PCR and was somewhat sensitive than one-step RT-PCR in detection of clinical samples. CONCLUSIONS: In this study, we have developed a new real-time RT-LAMP method, which is rapid, sensitive and efficient to detect PEDV.This method holds great promises not only in laboratory detection and discrimination of PEDV but also in large scale field and clinical studies.",2015 May 14,"['Yu, Xuewu', 'Shi, Lin', 'Lv, Xiaoping', 'Yao, Wei', 'Cao, Minghui', 'Yu, Hanxun', 'Wang, Xiurong', 'Zheng, Shimin']",Virol J,,,True
c444840c3b5380002dea23e1e8598f545a3470a5,PMC,Genomic Analysis and Surveillance of the Coronavirus Dominant in Ducks in China,http://dx.doi.org/10.1371/journal.pone.0129256,PMC4459809,26053682,CC BY,"The genetic diversity, evolution, distribution, and taxonomy of some coronaviruses dominant in birds other than chickens remain enigmatic. In this study we sequenced the genome of a newly identified coronavirus dominant in ducks (DdCoV), and performed a large-scale surveillance of coronaviruses in chickens and ducks using a conserved RT-PCR assay. The viral genome harbors a tandem repeat which is rare in vertebrate RNA viruses. The repeat is homologous to some proteins of various cellular organisms, but its origin remains unknown. Many substitutions, insertions, deletions, and some frameshifts and recombination events have occurred in the genome of the DdCoV, as compared with the coronavirus dominant in chickens (CdCoV). The distances between DdCoV and CdCoV are large enough to separate them into different species within the genus Gammacoronavirus. Our surveillance demonstrated that DdCoVs and CdCoVs belong to different lineages and occupy different ecological niches, further supporting that they should be classified into different species. Our surveillance also demonstrated that DdCoVs and CdCoVs are prevalent in live poultry markets in some regions of China. In conclusion, this study shed novel insight into the genetic diversity, evolution, distribution, and taxonomy of the coronaviruses circulating in chickens and ducks.",2015 Jun 8,"['Zhuang, Qing-Ye', 'Wang, Kai-Cheng', 'Liu, Shuo', 'Hou, Guang-Yu', 'Jiang, Wen-Ming', 'Wang, Su-Chun', 'Li, Jin-Ping', 'Yu, Jian-Min', 'Chen, Ji-Ming']",PLoS One,,,True
f3cbc0503581249a834895fc94cd3bae24714a0d,PMC,Which Kind of Provider’s Operation Volumes Matters? Associations between CABG Surgical Site Infection Risk and Hospital and Surgeon Operation Volumes among Medical Centers in Taiwan,http://dx.doi.org/10.1371/journal.pone.0129178,PMC4459823,26053035,CC BY,"BACKGROUND: Volume-infection relationships have been examined for high-risk surgical procedures, but the conclusions remain controversial. The inconsistency might be due to inaccurate identification of cases of infection and different methods of categorizing service volumes. This study takes coronary artery bypass graft (CABG) surgical site infections (SSIs) as an example to examine whether a relationship exists between operation volumes and SSIs, when different SSIs case identification, definitions and categorization methods of operation volumes were implemented. METHODS: A population-based cross-sectional multilevel study was conducted. A total of 7,007 patients who received CABG surgery between 2006 and 2008 from19 medical centers in Taiwan were recruited. SSIs associated with CABG surgery were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9 CM) codes and a Classification and Regression Trees (CART) model. Two definitions of surgeon and hospital operation volumes were used: (1) the cumulative CABG operation volumes within the study period; and (2) the cumulative CABG operation volumes in the previous one year before each CABG surgery. Operation volumes were further treated in three different ways: (1) a continuous variable; (2) a categorical variable based on the quartile; and (3) a data-driven categorical variable based on k-means clustering algorithm. Furthermore, subgroup analysis for comorbidities was also conducted. RESULTS: This study showed that hospital volumes were not significantly associated with SSIs, no matter which definitions or categorization methods of operation volume, or SSIs case identification approaches were used. On the contrary, the relationships between surgeon’s volumes varied. Most of the models demonstrated that the low-volume surgeons had higher risk than high-volume surgeons. CONCLUSION: Surgeon volumes were more important than hospital volumes in exploring the relationship between CABG operation volumes and SSIs in Taiwan. However, the relationships were not robust. Definitions and categorization methods of operation volume and correct identification of SSIs are important issues for future research.",2015 Jun 8,"['Yu, Tsung-Hsien', 'Tung, Yu-Chi', 'Chung, Kuo-Piao']",PLoS One,,,True
f0b1fa4036434b57c8307d43c39a4193f7e8053a,PMC,The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model,http://dx.doi.org/10.1371/journal.pone.0128794,PMC4459876,26053018,CC BY,"BACKGROUND: Carrageenan is a clinically proven and marketed compound for the treatment of viral upper respiratory tract infections. As infections caused by influenza virus are often accompanied by infections with other respiratory viruses the combination of a specific anti-influenza compound with the broadly active antiviral polymer has huge potential for the treatment of respiratory infections. Thus, the combination of the specific anti-influenza drug Zanamivir together with carrageenan in a formulation suitable for intranasal application was evaluated in-vitro and in-vivo. PRINCIPAL FINDINGS: We show in-vitro that carrageenan and Zanamivir act synergistically against several influenza A virus strains (H1N1(09)pdm, H3N2, H5N1, H7N7). Moreover, we demonstrate in a lethal influenza model with a low pathogenic H7N7 virus (HA closely related to the avian influenza A(H7N9) virus) and a H1N1(09)pdm influenza virus in C57BL/6 mice that the combined use of both compounds significantly increases survival of infected animals in comparison with both mono-therapies or placebo. Remarkably, this benefit is maintained even when the treatment starts up to 72 hours post infection. CONCLUSION: A nasal spray containing carrageenan and Zanamivir should therefore be tested for prevention and treatment of uncomplicated influenza in clinical trials.",2015 Jun 8,"['Morokutti-Kurz, Martina', 'König-Schuster, Marielle', 'Koller, Christiane', 'Graf, Christine', 'Graf, Philipp', 'Kirchoff, Norman', 'Reutterer, Benjamin', 'Seifert, Jan-Marcus', 'Unger, Hermann', 'Grassauer, Andreas', 'Prieschl-Grassauer, Eva', 'Nakowitsch, Sabine']",PLoS One,,,True
90403742f692b74ea175eef945ff8560a1a6c2b5,PMC,DNA transducer-triggered signal switch for visual colorimetric bioanalysis,http://dx.doi.org/10.1038/srep11190,PMC4462091,26060886,CC BY,"A simple and versatile colorimetric biosensor has been developed for sensitive and specific detection of a wide range of biomolecules, such as oligonucleotides and aptamer-recognized targets. Combining the signal transducer and catalyzed hairpin assembly (CHA)-based signal amplification, the target DNA binds with the hairpin DNA to form a new nucleic acid sequence and creates a toehold in the transducer for initiating the recycle amplification reaction of CHA. The catalyzed assembly process produces a large amount of G-rich DNA. In the presence of hemin, the G-rich DNA forms G-quadruplex/hemin complex and mimic horseradish peroxidase activity, which catalyzes a colorimetric reaction. Under optimal conditions, the calibration curve of synthetic target DNA has good linearity from 50 pM to 200 nM with a detection limit of 32 pM. This strategy has been successfully applied to detect S. pneumoniae as low as 156 CFU mL(−1), and shows a good specificity against closely related streptococci and major pathogenic bacteria. In addition, the developed method enables successful visual analysis of S. pneumoniae in clinical samples by the naked eye. Importantly, this method demonstrates excellent assay versatility for sensitively detecting oligonucleotides or aptamer-recognized targets.",2015 Jun 10,"['Chen, Wenhong', 'Yan, Yurong', 'Zhang, Ye', 'Zhang, Xuemei', 'Yin, Yibing', 'Ding, Shijia']",Sci Rep,,,True
2405180506967da1f4007e49ad653c3c356a823a,PMC,LeishVet update and recommendations on feline leishmaniosis,http://dx.doi.org/10.1186/s13071-015-0909-z,PMC4462189,26041555,CC BY,"Limited data is available on feline leishmaniosis (FeL) caused by Leishmania infantum worldwide. The LeishVet group presents in this report a review of the current knowledge on FeL, the epidemiological role of the cat in L. infantum infection, clinical manifestations, and recommendations on diagnosis, treatment and monitoring, prognosis and prevention of infection, in order to standardize the management of this disease in cats. The consensus of opinions and recommendations was formulated by combining a comprehensive review of evidence-based studies and case reports, clinical experience and critical consensus discussions. While subclinical feline infections are common in areas endemic for canine leishmaniosis, clinical illness due to L. infantum in cats is rare. The prevalence rates of feline infection with L. infantum in serological or molecular-based surveys range from 0 % to more than 60 %. Cats are able to infect sand flies and, therefore, they may act as a secondary reservoir, with dogs being the primary natural reservoir. The most common clinical signs and clinicopathological abnormalities compatible with FeL include lymph node enlargement and skin lesions such as ulcerative, exfoliative, crusting or nodular dermatitis (mainly on the head or distal limbs), ocular lesions (mainly uveitis), feline chronic gingivostomatitis syndrome, mucocutaneous ulcerative or nodular lesions, hypergammaglobulinaemia and mild normocytic normochromic anaemia. Clinical illness is frequently associated with impaired immunocompetence, as in case of retroviral coinfections or immunosuppressive therapy. Diagnosis is based on serology, polymerase chain reaction (PCR), cytology, histology, immunohistochemistry (IHC) or culture. If serological testing is negative or low positive in a cat with clinical signs compatible with FeL, the diagnosis of leishmaniosis should not be excluded and additional diagnostic methods (cytology, histology with IHC, PCR, culture) should be employed. The most common treatment used is allopurinol. Meglumine antimoniate has been administered in very few reported cases. Both drugs are administered alone and most cats recover clinically after therapy. Follow-up of treated cats with routine laboratory tests, serology and PCR is essential for prevention of clinical relapses. Specific preventative measures for this infection in cats are currently not available.",2015 Jun 4,"['Pennisi, Maria-Grazia', 'Cardoso, Luís', 'Baneth, Gad', 'Bourdeau, Patrick', 'Koutinas, Alek', 'Miró, Guadalupe', 'Oliva, Gaetano', 'Solano-Gallego, Laia']",Parasit Vectors,,,True
4b2ef217cb3fedccaffa0ecdd43344810630987b,PMC,Identification of human leukemia antigen A*0201-restricted epitopes derived from epidermal growth factor pathway substrate number 8,http://dx.doi.org/10.3892/mmr.2015.3673,PMC4463842,25936538,CC BY,"T-cell-mediated immunotherapy of hematological malignancies requires selection of targeted tumor-associated antigens and T-cell epitopes contained in these tumor proteins. Epidermal growth factor receptor pathway substrate 8 (EPS8), whose function is pivotal for tumor proliferation, progression and metastasis, has been found to be overexpressed in most human tumor types, while its expression in normal tissue is low. The aim of the present study was to identify human leukemia antigen (HLA)-A*0201-restricted epitopes of EPS8 by using a reverse immunology approach. To achieve this, computer algorithms were used to predict HLA-A*0201 molecular binding, proteasome cleavage patterns as well as translocation of transporters associated with antigen processing. Candidate peptides were experimentally validated by T2 binding affinity assay and brefeldin-A decay assay. The functional avidity of peptide-specific cytotoxic T lymphocytes (CTLs) induced from peripheral blood mononuclear cells of healthy volunteers were evaluated by using an enzyme-linked immunosorbent spot assay and a cytotoxicity assay. Four peptides, designated as P455, P92, P276 and P360, had high affinity and stability of binding towards the HLA-A*0201 molecule, and specific CTLs induced by them significantly responded to the corresponding peptides and secreted IFN-γ. At the same time, the CTLs were able to specifically lyse EPS8-expressing cell lines in an HLA-A*0201-restricted manner. The present study demon-strated that P455, P92, P276 and P360 were CTL epitopes of EPS8, and were able to be used for epitope-defined adoptive T-cell transfer and multi-epitope-based vaccine design.",2015 Aug 23,"['TANG, BAISHAN', 'ZHOU, WEIJUN', 'DU, JINGWEN', 'HE, YANJIE', 'LI, YUHUA']",Mol Med Rep,,,True
5f8c204d73feaf62ba6caa3be033d007e3134d5a,PMC,Dietary Sodium Suppresses Digestive Efficiency via the Renin-Angiotensin System,http://dx.doi.org/10.1038/srep11123,PMC4464075,26068176,CC BY,"Dietary fats and sodium are both palatable and are hypothesized to synergistically contribute to ingestive behavior and thereby obesity. Contrary to this hypothesis, C57BL/6J mice fed a 45% high fat diet exhibited weight gain that was inhibited by increased dietary sodium content. This suppressive effect of dietary sodium upon weight gain was mediated specifically through a reduction in digestive efficiency, with no effects on food intake behavior, physical activity, or resting metabolism. Replacement of circulating angiotensin II levels reversed the effects of high dietary sodium to suppress digestive efficiency. While the AT(1) receptor antagonist losartan had no effect in mice fed low sodium, the AT(2) receptor antagonist PD-123,319 suppressed digestive efficiency. Correspondingly, genetic deletion of the AT(2) receptor in FVB/NCrl mice resulted in suppressed digestive efficiency even on a standard chow diet. Together these data underscore the importance of digestive efficiency in the pathogenesis of obesity, and implicate dietary sodium, the renin-angiotensin system, and the AT(2) receptor in the control of digestive efficiency regardless of mouse strain or macronutrient composition of the diet. These findings highlight the need for greater understanding of nutrient absorption control physiology, and prompt more uniform assessment of digestive efficiency in animal studies of energy balance.",2015 Jun 11,"['Weidemann, Benjamin J.', 'Voong, Susan', 'Morales-Santiago, Fabiola I.', 'Kahn, Michael Z.', 'Ni, Jonathan', 'Littlejohn, Nicole K.', 'Claflin, Kristin E.', 'Burnett, Colin M.L.', 'Pearson, Nicole A.', 'Lutter, Michael L.', 'Grobe, Justin L.']",Sci Rep,,,True
0431672907f81802938cf3dd43fe76682469524d,PMC,Dietary Sodium Suppresses Digestive Efficiency via the Renin-Angiotensin System,http://dx.doi.org/10.1038/srep11123,PMC4464075,26068176,CC BY,"Dietary fats and sodium are both palatable and are hypothesized to synergistically contribute to ingestive behavior and thereby obesity. Contrary to this hypothesis, C57BL/6J mice fed a 45% high fat diet exhibited weight gain that was inhibited by increased dietary sodium content. This suppressive effect of dietary sodium upon weight gain was mediated specifically through a reduction in digestive efficiency, with no effects on food intake behavior, physical activity, or resting metabolism. Replacement of circulating angiotensin II levels reversed the effects of high dietary sodium to suppress digestive efficiency. While the AT(1) receptor antagonist losartan had no effect in mice fed low sodium, the AT(2) receptor antagonist PD-123,319 suppressed digestive efficiency. Correspondingly, genetic deletion of the AT(2) receptor in FVB/NCrl mice resulted in suppressed digestive efficiency even on a standard chow diet. Together these data underscore the importance of digestive efficiency in the pathogenesis of obesity, and implicate dietary sodium, the renin-angiotensin system, and the AT(2) receptor in the control of digestive efficiency regardless of mouse strain or macronutrient composition of the diet. These findings highlight the need for greater understanding of nutrient absorption control physiology, and prompt more uniform assessment of digestive efficiency in animal studies of energy balance.",2015 Jun 11,"['Weidemann, Benjamin J.', 'Voong, Susan', 'Morales-Santiago, Fabiola I.', 'Kahn, Michael Z.', 'Ni, Jonathan', 'Littlejohn, Nicole K.', 'Claflin, Kristin E.', 'Burnett, Colin M.L.', 'Pearson, Nicole A.', 'Lutter, Michael L.', 'Grobe, Justin L.']",Sci Rep,,,False
edcbcb53bfb68a6600dc092b57cf09b2a77ac86e,PMC,Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study,http://dx.doi.org/10.1371/journal.ppat.1004869,PMC4466531,26070066,CC0,"To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates.",2015 Jun 12,"['Zhai, Yijie', 'Franco, Luis M.', 'Atmar, Robert L.', 'Quarles, John M.', 'Arden, Nancy', 'Bucasas, Kristine L.', 'Wells, Janet M.', 'Niño, Diane', 'Wang, Xueqing', 'Zapata, Gladys E.', 'Shaw, Chad A.', 'Belmont, John W.', 'Couch, Robert B.']",PLoS Pathog,,,True
737e13b0236c1e2a6ada9c31ad3d8987a559b244,PMC,High Pulmonary Levels of IL-6 and IL-1β in Children with Chronic Suppurative Lung Disease Are Associated with Low Systemic IFN-γ Production in Response to Non-Typeable Haemophilus influenzae,http://dx.doi.org/10.1371/journal.pone.0129517,PMC4466570,26066058,CC BY,"Non-typeable Haemophilus influenzae (NTHi) is commonly associated with chronic suppurative lung disease in children. We have previously shown that children with chronic suppurative lung disease have a reduced capacity to produce IFN-γ in response to NTHi compared with healthy control children. The aim of this study was to determine if deficient NTHi-specific IFN-γ production is associated with heightened systemic or airway inflammation. We measured a panel of cytokines (IFN-γ, IL-1β, IL-6, IL-8, IL-12 p70), antimicrobial proteins (LL-37, IP-10) as well as cellular and clinical factors associated with airway and systemic inflammation in 70 children with chronic suppurative lung disease. IFN-γ was measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. Regression analysis was used to assess the association between the systemic and airway inflammation and the capacity to produce IFN-γ. On multivariate regression, NTHi-specific IFN-γ production was significantly negatively associated with the BAL concentrations of the inflammatory cytokines IL-6 (β=-0.316; 95%CI -0.49, -0.14; p=0.001) and IL-1β (β=-0.023; 95%CI -0.04, -0.01; p=0.001). This association was independent of bacterial or viral infection, BAL cellularity and the severity of bronchiectasis (using modified Bhalla score on chest CT scans). We found limited evidence of systemic inflammation in children with chronic suppurative lung disease. In summary, increased local airway inflammation is associated with a poorer systemic cell-mediated immune response to NTHi in children with chronic suppurative lung disease. These data support the emerging body of evidence that impaired cell-mediated immune responses and dysregulated airway inflammation may be linked and contribute to the pathobiology of chronic suppurative lung disease.",2015 Jun 12,"['Pizzutto, Susan J.', 'Upham, John W.', 'Yerkovich, Stephanie T.', 'Chang, Anne B.']",PLoS One,,,True
6331b16803abd3819dba628d339ffadbd2ad9a84,PMC,High Pulmonary Levels of IL-6 and IL-1β in Children with Chronic Suppurative Lung Disease Are Associated with Low Systemic IFN-γ Production in Response to Non-Typeable Haemophilus influenzae,http://dx.doi.org/10.1371/journal.pone.0129517,PMC4466570,26066058,CC BY,"Non-typeable Haemophilus influenzae (NTHi) is commonly associated with chronic suppurative lung disease in children. We have previously shown that children with chronic suppurative lung disease have a reduced capacity to produce IFN-γ in response to NTHi compared with healthy control children. The aim of this study was to determine if deficient NTHi-specific IFN-γ production is associated with heightened systemic or airway inflammation. We measured a panel of cytokines (IFN-γ, IL-1β, IL-6, IL-8, IL-12 p70), antimicrobial proteins (LL-37, IP-10) as well as cellular and clinical factors associated with airway and systemic inflammation in 70 children with chronic suppurative lung disease. IFN-γ was measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. Regression analysis was used to assess the association between the systemic and airway inflammation and the capacity to produce IFN-γ. On multivariate regression, NTHi-specific IFN-γ production was significantly negatively associated with the BAL concentrations of the inflammatory cytokines IL-6 (β=-0.316; 95%CI -0.49, -0.14; p=0.001) and IL-1β (β=-0.023; 95%CI -0.04, -0.01; p=0.001). This association was independent of bacterial or viral infection, BAL cellularity and the severity of bronchiectasis (using modified Bhalla score on chest CT scans). We found limited evidence of systemic inflammation in children with chronic suppurative lung disease. In summary, increased local airway inflammation is associated with a poorer systemic cell-mediated immune response to NTHi in children with chronic suppurative lung disease. These data support the emerging body of evidence that impaired cell-mediated immune responses and dysregulated airway inflammation may be linked and contribute to the pathobiology of chronic suppurative lung disease.",2015 Jun 12,"['Pizzutto, Susan J.', 'Upham, John W.', 'Yerkovich, Stephanie T.', 'Chang, Anne B.']",PLoS One,,,False
58a3c6aa227536fce49882de52254d61c1a6a0e2,PMC,High Pulmonary Levels of IL-6 and IL-1β in Children with Chronic Suppurative Lung Disease Are Associated with Low Systemic IFN-γ Production in Response to Non-Typeable Haemophilus influenzae,http://dx.doi.org/10.1371/journal.pone.0129517,PMC4466570,26066058,CC BY,"Non-typeable Haemophilus influenzae (NTHi) is commonly associated with chronic suppurative lung disease in children. We have previously shown that children with chronic suppurative lung disease have a reduced capacity to produce IFN-γ in response to NTHi compared with healthy control children. The aim of this study was to determine if deficient NTHi-specific IFN-γ production is associated with heightened systemic or airway inflammation. We measured a panel of cytokines (IFN-γ, IL-1β, IL-6, IL-8, IL-12 p70), antimicrobial proteins (LL-37, IP-10) as well as cellular and clinical factors associated with airway and systemic inflammation in 70 children with chronic suppurative lung disease. IFN-γ was measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. Regression analysis was used to assess the association between the systemic and airway inflammation and the capacity to produce IFN-γ. On multivariate regression, NTHi-specific IFN-γ production was significantly negatively associated with the BAL concentrations of the inflammatory cytokines IL-6 (β=-0.316; 95%CI -0.49, -0.14; p=0.001) and IL-1β (β=-0.023; 95%CI -0.04, -0.01; p=0.001). This association was independent of bacterial or viral infection, BAL cellularity and the severity of bronchiectasis (using modified Bhalla score on chest CT scans). We found limited evidence of systemic inflammation in children with chronic suppurative lung disease. In summary, increased local airway inflammation is associated with a poorer systemic cell-mediated immune response to NTHi in children with chronic suppurative lung disease. These data support the emerging body of evidence that impaired cell-mediated immune responses and dysregulated airway inflammation may be linked and contribute to the pathobiology of chronic suppurative lung disease.",2015 Jun 12,"['Pizzutto, Susan J.', 'Upham, John W.', 'Yerkovich, Stephanie T.', 'Chang, Anne B.']",PLoS One,,,False
ae7835c99d1391c53fec8da5b13783ebdd195223,PMC,Integrated travel network model for studying epidemics: Interplay between journeys and epidemic,http://dx.doi.org/10.1038/srep11401,PMC4466778,26073191,CC BY,"The ease of travelling between cities has contributed much to globalization. Yet, it poses a threat on epidemic outbreaks. It is of great importance for network science and health control to understand the impact of frequent journeys on epidemics. We stress that a new framework of modelling that takes a traveller’s viewpoint is needed. Such integrated travel network (ITN) model should incorporate the diversity among links as dictated by the distances between cities and different speeds of different modes of transportation, diversity among nodes as dictated by the population and the ease of travelling due to infrastructures and economic development of a city, and round-trip journeys to targeted destinations via the paths of shortest travel times typical of human journeys. An example is constructed for 116 cities in China with populations over one million that are connected by high-speed train services and highways. Epidemic spread on the constructed network is studied. It is revealed both numerically and theoretically that the traveling speed and frequency are important factors of epidemic spreading. Depending on the infection rate, increasing the traveling speed would result in either an enhanced or suppressed epidemic, while increasing the traveling frequency enhances the epidemic spreading.",2015 Jun 15,"['Ruan, Zhongyuan', 'Wang, Chaoqing', 'Ming Hui, Pak', 'Liu, Zonghua']",Sci Rep,,,True
cec3e151f7ac8b3a8766ac9fbc08c9429eaed31c,PMC,Integrated travel network model for studying epidemics: Interplay between journeys and epidemic,http://dx.doi.org/10.1038/srep11401,PMC4466778,26073191,CC BY,"The ease of travelling between cities has contributed much to globalization. Yet, it poses a threat on epidemic outbreaks. It is of great importance for network science and health control to understand the impact of frequent journeys on epidemics. We stress that a new framework of modelling that takes a traveller’s viewpoint is needed. Such integrated travel network (ITN) model should incorporate the diversity among links as dictated by the distances between cities and different speeds of different modes of transportation, diversity among nodes as dictated by the population and the ease of travelling due to infrastructures and economic development of a city, and round-trip journeys to targeted destinations via the paths of shortest travel times typical of human journeys. An example is constructed for 116 cities in China with populations over one million that are connected by high-speed train services and highways. Epidemic spread on the constructed network is studied. It is revealed both numerically and theoretically that the traveling speed and frequency are important factors of epidemic spreading. Depending on the infection rate, increasing the traveling speed would result in either an enhanced or suppressed epidemic, while increasing the traveling frequency enhances the epidemic spreading.",2015 Jun 15,"['Ruan, Zhongyuan', 'Wang, Chaoqing', 'Ming Hui, Pak', 'Liu, Zonghua']",Sci Rep,,,False
ff6f7ec41fcfb1353aea25253c33ae25469f6a07,PMC,Risky Bodies in the Plasma Bioeconomy: A Feminist Analysis,http://dx.doi.org/10.1177/1357034X13520331,PMC4467286,26097401,CC BY,"In 2003 the UK National Blood Service introduced a policy of ‘male donor preference’ which involved women’s plasma being discarded following blood collection. The policy was based on the view that data relating to the incidence of Transfusion-Related Acute Lung Injury (TRALI) was linked to transfusion with women’s plasma. While appearing to treat female donors as equal to male donors, exclusion criteria operate after donation at the stage of processing blood, thus perpetuating myths of universality even though only certain ‘extractions’ from women are retained for use in transfusion. Many women in the UK receive a plasma-derived product called Anti-D immunoglobulin which is manufactured from pooled male plasma. This article examines ways in which gender has significance for understanding blood relations, and how the blood economy is gendered. In our study of relations between blood donors and recipients, we explore how gendered bodies are produced through the discursive and material practices within blood services. We examine both how donation policies and the manufacturing and use of blood products produces gendered blood relations.",2015 Mar,"['Kent, Julie', 'Farrell, Anne-Maree']",Body Soc,,,True
05f2d4c337413ae496e31e2259020f3e328dcfa1,PMC,Recombinase Polymerase Amplification Assay for Rapid Diagnostics of Dengue Infection,http://dx.doi.org/10.1371/journal.pone.0129682,PMC4468249,26075598,CC BY,"BACKGROUND: Over 2.5 billion people are exposed to the risk of contracting dengue fever (DF). Early diagnosis of DF helps to diminish its burden on public health. Real-time reverse transcription polymerase amplification assays (RT-PCR) are the standard method for molecular detection of the dengue virus (DENV). Real-time RT-PCR analysis is not suitable for on-site screening since mobile devices are large, expensive, and complex. In this study, two RT-recombinase polymerase amplification (RT-RPA) assays were developed to detect DENV1-4. METHODOLOGY/PRINCIPAL FINDINGS: Using two quantitative RNA molecular standards, the analytical sensitivity of a RT-RPA targeting the 3´non-translated region of DENV1-4 was found to range from 14 (DENV4) to 241 (DENV1-3) RNA molecules detected. The assay was specific and did not cross detect other Flaviviruses. The RT-RPA assay was tested in a mobile laboratory combining magnetic-bead based total nucleic acid extraction and a portable detection device in Kedougou (Senegal) and in Bangkok (Thailand). In Kedougou, the RT-RPA was operated at an ambient temperature of 38°C with auxiliary electricity tapped from a motor vehicle and yielded a clinical sensitivity and specificity of 98% (n=31) and 100% (n=23), respectively. While in the field trial in Bangkok, the clinical sensitivity and specificity were 72% (n=90) and 100%(n=41), respectively. CONCLUSIONS/SIGNIFICANCE: During the first 5 days of infection, the developed DENV1-4 RT-RPA assays constitute a suitable accurate and rapid assay for DENV diagnosis. Moreover, the use of a portable fluorescence-reading device broadens its application potential to the point-of-care for outbreak investigations.",2015 Jun 15,"['Abd El Wahed, Ahmed', 'Patel, Pranav', 'Faye, Oumar', 'Thaloengsok, Sasikanya', 'Heidenreich, Doris', 'Matangkasombut, Ponpan', 'Manopwisedjaroen, Khajohnpong', 'Sakuntabhai, Anavaj', 'Sall, Amadou A.', 'Hufert, Frank T.', 'Weidmann, Manfred']",PLoS One,,,True
43c284998733a1d7cc474d14c378f08e4b509c63,PMC,Antiviral activity of silymarin against chikungunya virus,http://dx.doi.org/10.1038/srep11421,PMC4468427,26078201,CC BY,"The mosquito-borne chikungunya virus (CHIKV) causes chikungunya fever, with clinical presentations such as severe back and small joint pain, and debilitating arthritis associated with crippling pains that persist for weeks and even years. Although there are several studies to evaluate the efficacy of drugs against CHIKV, the treatment for chikungunya fever is mainly symptom-based and no effective licensed vaccine or antiviral are available. Here, we investigated the antiviral activity of three types of flavonoids against CHIKV in vitro replication. Three compounds: silymarin, quercetin and kaempferol were evaluated for their in vitro antiviral activities against CHIKV using a CHIKV replicon cell line and clinical isolate of CHIKV of Central/East African genotype. A cytopathic effect inhibition assay was used to determine their activities on CHIKV viral replication and quantitative reverse transcription PCR was used to calculate virus yield. Antiviral activity of effective compound was further investigated by evaluation of CHIKV protein expression using western blotting for CHIKV nsP1, nsP3, and E2E1 proteins. Briefly, silymarin exhibited significant antiviral activity against CHIKV, reducing both CHIKV replication efficiency and down-regulating production of viral proteins involved in replication. This study may have important consequence for broaden the chance of getting the effective antiviral for CHIKV infection.",2015 Jun 16,"['Lani, Rafidah', 'Hassandarvish, Pouya', 'Chiam, Chun Wei', 'Moghaddam, Ehsan', 'Chu, Justin Jang Hann', 'Rausalu, Kai', 'Merits, Andres', 'Higgs, Stephen', 'Vanlandingham, Dana', 'Abu Bakar, Sazaly', 'Zandi, Keivan']",Sci Rep,,,True
6a3acbb2d3cf75b9cb9221b0d8acc32559ec4cf8,PMC,Apolipoprotein D Transgenic Mice Develop Hepatic Steatosis through Activation of PPARγ and Fatty Acid Uptake,http://dx.doi.org/10.1371/journal.pone.0130230,PMC4470830,26083030,CC BY,"Transgenic mice (Tg) overexpressing human apolipoprotein D (H-apoD) in the brain are resistant to neurodegeneration. Despite the use of a neuron-specific promoter to generate the Tg mice, they expressed significant levels of H-apoD in both plasma and liver and they slowly develop hepatic steatosis and insulin resistance. We show here that hepatic PPARγ expression in Tg mice is increased by 2-fold compared to wild type (WT) mice. Consequently, PPARγ target genes Plin2 and Cide A/C are overexpressed, leading to increased lipid droplets formation. Expression of the fatty acid transporter CD36, another PPARgamma target, is also increased in Tg mice associated with elevated fatty acid uptake as measured in primary hepatocytes. Elevated expression of AMPK in the liver of Tg leads to phosphorylation of acetyl CoA carboxylase, indicating a decreased activity of the enzyme. Fatty acid synthase expression is also induced but the hepatic lipogenesis measured in vivo is not significantly different between WT and Tg mice. In addition, expression of carnitine palmitoyl transferase 1, the rate-limiting enzyme of beta-oxidation, is slightly upregulated. Finally, we show that overexpressing H-apoD in HepG2 cells in presence of arachidonic acid (AA), the main apoD ligand, increases the transcriptional activity of PPARγ. Supporting the role of apoD in AA transport, we observed enrichment in hepatic AA and a decrease in plasmatic AA concentration. Taken together, our results demonstrate that the hepatic steatosis observed in apoD Tg mice is a consequence of increased PPARγ transcriptional activity by AA leading to increased fatty acid uptake by the liver.",2015 Jun 17,"['Labrie, Marilyne', 'Lalonde, Simon', 'Najyb, Ouafa', 'Thiery, Maxime', 'Daneault, Caroline', 'Des Rosiers, Chrisitne', 'Rassart, Eric', 'Mounier, Catherine']",PLoS One,,,True
d3adf3be72d751812577d37b2f3db193b2b93cc2,PMC,"Alternative divalent cations (Zn(2+), Co(2+), and Mn(2+)) are not mutagenic at conditions optimal for HIV-1 reverse transcriptase activity",http://dx.doi.org/10.1186/s12858-015-0041-x,PMC4472245,25934642,CC BY,"BACKGROUND: Fidelity of DNA polymerases can be influenced by cation co-factors. Physiologically, Mg(2+) is used as a co-factor by HIV reverse transcriptase (RT) to perform catalysis; however, alternative cations including Mn(2+), Co(2+), and Zn(2+) can also support catalysis. Although Zn(2+) supports DNA synthesis, it inhibits HIV RT by significantly modifying RT catalysis. Zn(2+) is currently being investigated as a component of novel treatment options against HIV and we wanted to investigate the fidelity of RT with Zn(2+). METHODS: We used PCR-based and plasmid-based alpha complementation assays as well as steady-state misinsertion and misincorporation assays to examine the fidelity of RT with Mn(2+), Co(2+), and Zn(2+). RESULTS: The fidelity of DNA synthesis by HIV-1 RT was approximately 2.5 fold greater in Zn(2+) when compared to Mg(2+) at cation conditions optimized for nucleotide catalysis. Consistent with this, RT extended primers with mismatched 3′ nucleotides poorly and inserted incorrect nucleotides less efficiently using Zn(2+) than Mg(2+). In agreement with previous literature, we observed that Mn(2+) and Co(2+) dramatically decreased the fidelity of RT at highly elevated concentrations (6 mM). However, surprisingly, the fidelity of HIV RT with Mn(2+) and Co(2+) remained similar to Mg(2+) at lower concentrations that are optimal for catalysis. CONCLUSION: This study shows that Zn(2+), at optimal extension conditions, increases the fidelity of HIV-1 RT and challenges the notion that alternative cations capable of supporting polymerase catalysis are inherently mutagenic.",2015 May 3,"['Achuthan, Vasudevan', 'DeStefano, Jeffrey J']",BMC Biochem,,,True
51c863bc37f993b3da543b91458e3ed5abd9aba9,PMC,Pathology in Captive Wild Felids at German Zoological Gardens,http://dx.doi.org/10.1371/journal.pone.0130573,PMC4472349,26086731,CC BY,"This retrospective study provides an overview on spontaneous diseases occurring in 38 captive wild felids submitted for necropsy by German zoological gardens between 2004 and 2013. Species included 18 tigers, 8 leopards, 7 lions, 3 cheetahs and 2 cougars with an age ranging from 0.5 to 22 years. Renal lesions, predominantly tubular alterations (intra-tubular concrements, tubular degeneration, necrosis, intra-tubular cellular debris, proteinaceous casts, dilated tubuli) followed by interstitial (lympho-plasmacytic inflammation, fibrosis, metastatic-suppurative inflammation, eosinophilic inflammation) and glomerular lesions (glomerulonephritis, glomerulosclerosis, amyloidosis) were detected in 33 out of 38 animals (87%). Tumors were found in 19 of 38 felids (50%) with 12 animals showing more than one neoplasm. The tumor prevalence increased with age. Neoplasms originated from endocrine (11), genital (8), lympho-hematopoietic (5) and alimentary organs (4) as well as the mesothelium (3). Most common neoplasms comprised uterine/ovarian leiomyomas (5/2), thyroid adenomas/adenocarcinoma (5/1), pleural mesotheliomas (3), hemangiosarcomas (2) and glossal papillomas (2). Inflammatory changes were frequently encountered in the intestine and the lung. Two young animals displayed metastatic mineralization suggestive of a vitamin D- or calcium intoxication. One tiger exhibited degenerative white matter changes consistent with an entity termed large felid leukoencephalomyelopathy. Various hyperplastic, degenerative and inflammatory changes with minor clinical significance were found in several organs. Summarized, renal lesions followed by neoplastic changes as well as inflammatory changes in lung and gastrointestinal tract represent the most frequent findings in captive wild felids living in German zoological gardens.",2015 Jun 18,"['Junginger, Johannes', 'Hansmann, Florian', 'Herder, Vanessa', 'Lehmbecker, Annika', 'Peters, Martin', 'Beyerbach, Martin', 'Wohlsein, Peter', 'Baumgärtner, Wolfgang']",PLoS One,,,True
710a40e33a20fe517c78c06748005fea78f21105,PMC,Chloroquine and beyond: exploring anti-rheumatic drugs to reduce immune hyperactivation in HIV/AIDS,http://dx.doi.org/10.1186/s12977-015-0178-0,PMC4472405,26084487,CC BY,"The restoration of the immune system prompted by antiretroviral therapy (ART) has allowed drastically reducing the mortality and morbidity of HIV infection. However, one main source of clinical concern is the persistence of immune hyperactivation in individuals under ART. Chronically enhanced levels of T-cell activation are associated with several deleterious effects which lead to faster disease progression and slower CD4(+) T-cell recovery during ART. In this article, we discuss the rationale, and review the results, of the use of antimalarial quinolines, such as chloroquine and its derivative hydroxychloroquine, to counteract immune activation in HIV infection. Despite the promising results of several pilot trials, the most recent clinical data indicate that antimalarial quinolines are unlikely to exert a marked beneficial effect on immune activation. Alternative approaches will likely be required to reproducibly decrease immune activation in the setting of HIV infection. If the quinoline-based strategies should nevertheless be pursued in future studies, particular care must be devoted to the dosage selection, in order to maximize the chances to obtain effective in vivo drug concentrations.",2015 Jun 18,"['Savarino, Andrea', 'Shytaj, Iart Luca']",Retrovirology,,,True
1f63075aa219ae29132b49a0c7277632b9b31ba8,PMC,"A survey of UK acute clinicians' knowledge of personal protective requirements for infectious diseases and chemical, biological, and radiological warfare agents",http://dx.doi.org/10.1186/cc14166,PMC4472707,,CC BY,,2015 Mar 16,"['Bond, AR', 'Buckingham, A', 'Schumacher, J']",Crit Care,,,True
802ec789744669d95c380885412457a648a10e0d,PMC,Hepatitis C virus and host cell nuclear transport machinery: a clandestine affair,http://dx.doi.org/10.3389/fmicb.2015.00619,PMC4472997,26150811,CC BY,"There is growing evidence that factors encoded by cytoplasmic replicating viruses functionally interact with components of the nucleocytoplasmic transport apparatus. They do so either to access the cell nucleus, thus affecting genes expression, or to interfere with nuclear transport functionality, hindering host immune response. Recent studies revealed that the hepatitis C virus (HCV) makes no exception, interacting with the host cell nuclear transport machinery at two different levels. On the one hand, small amounts of both core and NS5A localize within the host cell nucleus during productive infection, modulating gene expression and signaling functions to promote persistent infection. On the other hand, HCV infection causes a profound redistribution of certain nucleoproteins to the close proximity of endoplasmic reticulum membrane-derived viral replication factories, where viral RNA amplification occurs. These nucleoporins are believed to form nuclear pore complex-like structures, as suggested by their ability to recruit nuclear localization sequence-bearing proteins. Thus, both processes are linked to virus-induced persistence and pathogenesis, representing possible targets for the development of novel anti-HCV therapeutics.",2015 Jun 19,"['Bonamassa, Barbara', 'Ciccarese, Francesco', 'Antonio, Veronica Di', 'Contarini, Andrea', 'Palù, Giorgio', 'Alvisi, Gualtiero']",Front Microbiol,,,True
d480419719edb5f4d35e01306133b919c1474f89,PMC,BoHV-4-Based Vector Single Heterologous Antigen Delivery Protects STAT1((-/-)) Mice from Monkeypoxvirus Lethal Challenge,http://dx.doi.org/10.1371/journal.pntd.0003850,PMC4473039,26086739,CC BY,"Monkeypox virus (MPXV) is the etiological agent of human (MPX). It is an emerging orthopoxvirus zoonosis in the tropical rain forest of Africa and is endemic in the Congo-basin and sporadic in West Africa; it remains a tropical neglected disease of persons in impoverished rural areas. Interaction of the human population with wildlife increases human infection with MPX virus (MPXV), and infection from human to human is possible. Smallpox vaccination provides good cross-protection against MPX; however, the vaccination campaign ended in Africa in 1980, meaning that a large proportion of the population is currently unprotected against MPXV infection. Disease control hinges on deterring zoonotic exposure to the virus and, barring that, interrupting person-to-person spread. However, there are no FDA-approved therapies against MPX, and current vaccines are limited due to safety concerns. For this reason, new studies on pathogenesis, prophylaxis and therapeutics are still of great interest, not only for the scientific community but also for the governments concerned that MPXV could be used as a bioterror agent. In the present study, a new vaccination strategy approach based on three recombinant bovine herpesvirus 4 (BoHV-4) vectors, each expressing different MPXV glycoproteins, A29L, M1R and B6R were investigated in terms of protection from a lethal MPXV challenge in STAT1 knockout mice. BoHV-4-A-CMV-A29LgD(106)ΔTK, BoHV-4-A-EF1α-M1RgD(106)ΔTK and BoHV-4-A-EF1α-B6RgD(106)ΔTK were successfully constructed by recombineering, and their capacity to express their transgene was demonstrated. A small challenge study was performed, and all three recombinant BoHV-4 appeared safe (no weight-loss or obvious adverse events) following intraperitoneal administration. Further, BoHV-4-A-EF1α-M1RgD(106)ΔTK alone or in combination with BoHV-4-A-CMV-A29LgD(106)ΔTK and BoHV-4-A-EF1α-B6RgD(106)ΔTK, was shown to be able to protect, 100% alone and 80% in combination, STAT1((-/-)) mice against mortality and morbidity. This work demonstrated the efficacy of BoHV-4 based vectors and the use of BoHV-4 as a vaccine-vector platform.",2015 Jun 18,"['Franceschi, Valentina', 'Parker, Scott', 'Jacca, Sarah', 'Crump, Ryan W.', 'Doronin, Konstantin', 'Hembrador, Edguardo', 'Pompilio, Daniela', 'Tebaldi, Giulia', 'Estep, Ryan D.', 'Wong, Scott W.', 'Buller, Mark R.', 'Donofrio, Gaetano']",PLoS Negl Trop Dis,,,True
d44ccd4da37549d25e916096ebd616c982af0422,PMC,In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses,http://dx.doi.org/10.1038/srep11434,PMC4473683,26091504,CC BY,"Newly emerging influenza A viruses (IAV) pose a major threat to human health by causing seasonal epidemics and/or pandemics, the latter often facilitated by the lack of pre-existing immunity in the general population. Early recognition of candidate pandemic influenza viruses (CPIV) is of crucial importance for restricting virus transmission and developing appropriate therapeutic and prophylactic strategies including effective vaccines. Often, the pandemic potential of newly emerging IAV is only fully recognized once the virus starts to spread efficiently causing serious disease in humans. Here, we used a novel phylogenetic algorithm based on the informational spectrum method (ISM) to identify potential CPIV by predicting mutations in the viral hemagglutinin (HA) gene that are likely to (differentially) affect critical interactions between the HA protein and target cells from bird and human origin, respectively. Predictions were subsequently validated by generating pseudotyped retrovirus particles and genetically engineered IAV containing these mutations and characterizing potential effects on virus entry and replication in cells expressing human and avian IAV receptors, respectively. Our data suggest that the ISM-based algorithm is suitable to identify CPIV among IAV strains that are circulating in animal hosts and thus may be a new tool for assessing pandemic risks associated with specific strains.",2015 Jun 19,"['Schmier, Sonja', 'Mostafa, Ahmed', 'Haarmann, Thomas', 'Bannert, Norbert', 'Ziebuhr, John', 'Veljkovic, Veljko', 'Dietrich, Ursula', 'Pleschka, Stephan']",Sci Rep,,,True
16853d835bfed5ec948486100159cebdc5435477,PMC,In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses,http://dx.doi.org/10.1038/srep11434,PMC4473683,26091504,CC BY,"Newly emerging influenza A viruses (IAV) pose a major threat to human health by causing seasonal epidemics and/or pandemics, the latter often facilitated by the lack of pre-existing immunity in the general population. Early recognition of candidate pandemic influenza viruses (CPIV) is of crucial importance for restricting virus transmission and developing appropriate therapeutic and prophylactic strategies including effective vaccines. Often, the pandemic potential of newly emerging IAV is only fully recognized once the virus starts to spread efficiently causing serious disease in humans. Here, we used a novel phylogenetic algorithm based on the informational spectrum method (ISM) to identify potential CPIV by predicting mutations in the viral hemagglutinin (HA) gene that are likely to (differentially) affect critical interactions between the HA protein and target cells from bird and human origin, respectively. Predictions were subsequently validated by generating pseudotyped retrovirus particles and genetically engineered IAV containing these mutations and characterizing potential effects on virus entry and replication in cells expressing human and avian IAV receptors, respectively. Our data suggest that the ISM-based algorithm is suitable to identify CPIV among IAV strains that are circulating in animal hosts and thus may be a new tool for assessing pandemic risks associated with specific strains.",2015 Jun 19,"['Schmier, Sonja', 'Mostafa, Ahmed', 'Haarmann, Thomas', 'Bannert, Norbert', 'Ziebuhr, John', 'Veljkovic, Veljko', 'Dietrich, Ursula', 'Pleschka, Stephan']",Sci Rep,,,False
5f88f46f2e2fe48b05a5cfefcfbe74f4bc90f574,PMC,Malaria and the mobile and migrant population in Cambodia: a population movement framework to inform strategies for malaria control and elimination,http://dx.doi.org/10.1186/s12936-015-0773-5,PMC4474346,26088924,CC BY,"BACKGROUND: The relationships between human population movement (HPM) and health are a concern at global level. In the case of malaria, those links are crucial in relation to the spread of drug resistant parasites and to the elimination of malaria in the Greater Mekong sub-Region (GMS) and beyond. The mobile and migrant populations (MMP) who are involved in forest related activities are both at high risk of being infected with malaria and at risk of receiving late and sub-standard treatment due to poor access to health services. In Cambodia, in 2012, the National Malaria Control Programme (NMCP) identified, as a key objective, the development of a specific strategy for MMPs in order to address these challenges. A population movement framework (PMF) for malaria was developed and operationalized in order to contribute to this strategy. METHODS: A review of the published and unpublished literature was conducted. Based on a synthesis of the results, information was presented and discussed with experienced researchers and programme managers in the Cambodian NMCP and led to the development and refinement of a PMF for malaria. The framework was “tested” for face and content validity with national experts through a workshop approach. RESULTS: In the literature, HPM has been described using various spatial and temporal dimensions both in the context of the spread of anti-malarial drug resistance, and in the context of malaria elimination and previous classifications have categorized MMPs in Cambodia and the GMS through using a number of different criteria. Building on these previous models, the PMF was developed and then refined and populated with in-depth information relevant to Cambodia collected from social science research and field experiences in Cambodia. The framework comprises of the PMF itself, MMP activity profiles and a Malaria Risk Index which is a summation of three related indices: a vulnerability index, an exposure index and an access index which allow a qualitative ranking of malaria risk in the MMP population. Application of currently available data to the framework illustrates that the highest risk population are those highly mobile populations engaged in forest work. CONCLUSION: This paper describes the process of defining MMPs in Cambodia, identifying the different activities and related risks to appropriately target and tailor interventions to the highest risk groups. The framework has been used to develop more targeted behaviour change and outreach interventions for MMPs in Cambodia and its utility and effectiveness will be evaluated as part of those interventions.",2015 Jun 20,"['Guyant, Philippe', 'Canavati, Sara E', 'Chea, Nguon', 'Ly, Po', 'Whittaker, Maxine Anne', 'Roca-Feltrer, Arantxa', 'Yeung, Shunmay']",Malar J,,,True
5d76f48664d2e90c67768d51a2efda3e12c316ce,PMC,Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance,http://dx.doi.org/10.1111/irv.12315,PMC4474494,25912617,CC BY,"The 2009 influenza A(H1N1)pdm09 pandemic highlighted the need for improved scientific knowledge to support better pandemic preparedness and seasonal influenza control. The Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) project, a 5-year (2012–2016) multiagency and multidisciplinary collaboration, aimed to measure disease burden, epidemiology, aetiology, risk factors, immunology, effectiveness of vaccination and other prevention strategies for influenza and other respiratory infectious diseases of public health importance. Two active, prospective, population-based surveillance systems were established for monitoring influenza and other respiratory pathogens among those hospitalized patients with acute respiratory illness and those enrolled patients seeking consultations at sentinel general practices. In 2015, a sero-epidemiological study will use a sample of patients from the same practices. These data will provide a full picture of the disease burden and risk factors from asymptomatic infections to severe hospitalized disease and deaths and related economic burden. The results during the first 2 years (2012–2013) provided scientific evidence to (a) support a change to NZ's vaccination policy for young children due to high influenza hospitalizations in these children; (b) contribute to the revision of the World Health Organization's case definition for severe acute respiratory illness for global influenza surveillance; and (c) contribute in part to vaccine strain selection using vaccine effectiveness assessment in the prevention of influenza-related consultations and hospitalizations. In summary, SHIVERS provides valuable international platforms for supporting seasonal influenza control and pandemic preparedness, and responding to other emerging/endemic respiratory-related infections.",2015 Jul 9,"['Huang, Qiu Sue', 'Turner, Nikki', 'Baker, Michael G', 'Williamson, Deborah A', 'Wong, Conroy', 'Webby, Richard', 'Widdowson, Marc-Alain']",Influenza Other Respir Viruses,,,True
bfbee300d5a290a823a6a06f268e8a02a7e47455,PMC,Clinical differences between respiratory viral and bacterial mono- and dual pathogen detected among Singapore military servicemen with febrile respiratory illness,http://dx.doi.org/10.1111/irv.12312,PMC4474496,25827870,CC BY,"BACKGROUND: Although it is known that febrile respiratory illnesses (FRI) may be caused by multiple respiratory pathogens, there are no population-level studies describing its impact on clinical disease. METHODS: Between May 2009 and October 2012, 7733 FRI patients and controls in the Singapore military had clinical data and nasal wash samples collected prospectively and sent for PCR testing. Patients with one pathogen detected (mono-pathogen) were compared with those with two pathogens (dual pathogen) for differences in basic demographics and clinical presentation. RESULTS: In total, 45.8% had one pathogen detected, 20.2% had two pathogens detected, 30.9% had no pathogens detected, and 3.1% had more than two pathogens. Multiple pathogens were associated with recruits, those with asthma and non-smokers. Influenza A (80.0%), influenza B (73.0%) and mycoplasma (70.6%) were most commonly associated with mono-infections, while adenovirus was most commonly associated with dual infections (62.9%). Influenza A paired with S. pneumoniae had higher proportions of chills and rigors than their respective mono-pathogens (P = 0.03, P = 0.009). H. influenzae paired with either enterovirus or parainfluenzae had higher proportions of cough with phlegm than their respective mono-pathogens. Although there were observed differences in mean proportions of body temperature, nasal symptoms, sore throat, body aches and joint pains between viral and bacterial mono-pathogens, there were few differences between distinct dual-pathogen pairs and their respective mono-pathogen counterparts. CONCLUSION: A substantial number of FRI patients have multiple pathogens detected. Observed clinical differences between patients of dual pathogen and mono-pathogen indicate the likely presence of complex microbial interactions between the various pathogens.",2015 Jul 9,"['Ho, Zheng Jie Marc', 'Zhao, Xiahong', 'Cook, Alex R', 'Loh, Jin Phang', 'Ng, Sock Hoon', 'Tan, Boon Huan', 'Lee, Vernon J']",Influenza Other Respir Viruses,,,True
3a6c69f2092011505ba1b80bb57f88732b42789c,PMC,Middle East respiratory syndrome coronavirus (MERS-Cov) screening of exposed healthcare workers in a tertiary care hospital in Saudi Arabia,http://dx.doi.org/10.1186/2047-2994-4-S1-O57,PMC4474819,,CC BY,,2015 Jun 16,"['Alameer, K', 'Abukhzam, B', 'Khan, W', 'El-Saed, A', 'Balkhy, H']",Antimicrob Resist Infect Control,,,False
dd3e3bb5844179f4fc6f507e88369030c9efed74,PMC,Infection prevention and control strategies for the Middle East respiratory syndrome coronavirus and outcome in Oman,http://dx.doi.org/10.1186/2047-2994-4-S1-O58,PMC4474925,,CC BY,,2015 Jun 16,"['Al Harthy, KSA', 'Al Maani, A', 'Elsheikh, M']",Antimicrob Resist Infect Control,,,False
918a69132dead88bca9d30666a4eb1d3834206a6,PMC,"Current knowledge, attitude and behaviour of hand and food hygiene in a developed residential community of Singapore: a cross-sectional survey",http://dx.doi.org/10.1186/s12889-015-1910-3,PMC4475322,26093582,CC BY,"BACKGROUND: Diarrhoea incidence has been increasing progressively over the past years in developed countries, including Singapore, despite the accessibility and availability to clean water, well-established sanitation infrastructures and regular hygiene promotion. The aim of this study is to determine the current knowledge, attitude and behaviour of hand and food hygiene, and the potential risk factors of diarrhoea in a residential community of Singapore. METHODS: A cross-sectional study was conducted within a residential area in the west of Singapore from June to August 2013. A total of 1,156 household units were randomly sampled and invited to participate in an interviewer-assisted survey using standardised questionnaires. Descriptive, univariate and multivariate analyses were performed using descriptive statistics, Fisher’s Exact test and multivariate logistic regression modelling, respectively. R program was used for all statistical analysis. All tests were conducted at 5 % level of significance with 95 % confidence intervals (CI) reported where applicable. RESULTS: A total of 240 units (20.8 %) consented and responded to the survey invitation. About 77 % of the expected knowledge and attitude were observed in at least 80 % of the participants, compared to only about 31 % of the expected behaviours and practises. Being single [adjusted odds ratio (AOR) = 2.29; 95 % CI = 1.16-4.48], having flu in the past six month (AOR = 3.24; 95 % CI = 1.74-6.06), preferred self-medication (AOR = 2.07; 95 % CI = 1.06–4.12) were risk factors of diarrhoea. Washing hands with water before attending to children or sick persons (AOR = 0.30; 95 % CI = 0.11–0.82), washing hands with water (AOR = 0.16; 95 % CI = 0.05–0.45) and water with soap (AOR = 0.29; 95 % CI = 0.12–0.72) after attending to children or sick persons, and hand washing between 30 s to a minute (AOR = 0.44; 95 % CI = 0.20-0.90) were protective factors against diarrhoea. CONCLUSIONS: Good knowledge and attitude of the participants did not positively translate into high compliance and motivation to perform good hygiene practices. This observation may have resulted in a significant extent on the increasing diarrhoea incidences. Current interventions may be improved with more active community partnership among the residents, schools and the relevant social organizations, to raise awareness on the importance of compliance to good hygiene practices, and the risk factors of diarrhoea. A large case–control study would be required to validate these findings in future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-1910-3) contains supplementary material, which is available to authorized users.",2015 Jun 21,"['Pang, Junxiong', 'Chua, Shao Wei Jonathan Lumen', 'Hsu, Liyang']",BMC Public Health,,,True
6d86f444589890a4657acab7888a38806287387e,PMC,Characterization of the bacterial gut microbiota of piglets suffering from new neonatal porcine diarrhoea,http://dx.doi.org/10.1186/s12917-015-0419-4,PMC4476181,26099928,CC BY,"BACKGROUND: In recent years, new neonatal porcine diarrhoea (NNPD) of unknown aetiology has emerged in Denmark. NNPD affects piglets during the first week of life and results in impaired welfare, decreased weight gain, and in the worst-case scenario death. Commonly used preventative interventions such as vaccination or treatment with antibiotics, have a limited effect on NNPD. Previous studies have investigated the clinical manifestations, histopathology, and to some extent, microbiological findings; however, these studies were either inconclusive or suggested that Enterococci, possibly in interaction with Escherichia coli, contribute to the aetiology of NNPD. This study examined ileal and colonic luminal contents of 50 control piglets and 52 NNPD piglets by means of the qPCR-based Gut Microbiotassay and 16 samples by 454 sequencing to study the composition of the bacterial gut microbiota in relation to NNPD. RESULTS: NNPD was associated with a diminished quantity of bacteria from the phyla Actinobacteria and Firmicutes while genus Enterococcus was more than 24 times more abundant in diarrhoeic piglets. The number of bacteria from the phylum Fusobacteria was also doubled in piglets suffering from diarrhoea. With increasing age, the gut microbiota of NNPD affected piglet and control piglets became more diverse. Independent of diarrhoeic status, piglets from first parity sows (gilts) possessed significantly more bacteria from family Enterobacteriaceae and species E. coli, and fewer bacteria from phylum Firmicutes. Piglets born to gilts had 25 times higher odds of having NNPD compared with piglets born to multiparous sows. Finally, the co-occurrence of genus Enterococcus and species E. coli contributed to the risk of having NNPD. CONCLUSION: The results of this study support previous findings that points towards genus Enterococcus and species E. coli to be involved in the pathogenesis of NNPD. Moreover, the results indicate that NNPD is associated with a disturbed bacterial composition and larger variation between the diarrhoeic piglets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0419-4) contains supplementary material, which is available to authorized users.",2015 Jun 23,"['Hermann-Bank, Marie Louise', 'Skovgaard, Kerstin', 'Stockmarr, Anders', 'Strube, Mikael Lenz', 'Larsen, Niels', 'Kongsted, Hanne', 'Ingerslev, Hans-Christian', 'Mølbak, Lars', 'Boye, Mette']",BMC Vet Res,,,True
82d76d619e7be4f0ef2490f933d140ec9f722a55,PMC,Genetic drift of human coronavirus OC43 spike gene during adaptive evolution,http://dx.doi.org/10.1038/srep11451,PMC4476415,26099036,CC BY,"Coronaviruses (CoVs) continuously threaten human health. However, to date, the evolutionary mechanisms that govern CoV strain persistence in human populations have not been fully understood. In this study, we characterized the evolution of the major antigen-spike (S) gene in the most prevalent human coronavirus (HCoV) OC43 using phylogenetic and phylodynamic analysis. Among the five known HCoV-OC43 genotypes (A to E), higher substitution rates and dN/dS values as well as more positive selection sites were detected in the S gene of genotype D, corresponding to the most dominant HCoV epidemic in recent years. Further analysis showed that the majority of substitutions were located in the S1 subunit. Among them, seven positive selection sites were chronologically traced in the temporal evolution routes of genotype D, and six were located around the critical sugar binding region in the N-terminal domain (NTD) of S protein, an important sugar binding domain of CoV. These findings suggest that the genetic drift of the S gene may play an important role in genotype persistence in human populations, providing insights into the mechanisms of HCoV-OC43 adaptive evolution.",2015 Jun 22,"['Ren, Lili', 'Zhang, Yue', 'Li, Jianguo', 'Xiao, Yan', 'Zhang, Jing', 'Wang, Ying', 'Chen, Lan', 'Paranhos-Baccalà, Gláucia', 'Wang, Jianwei']",Sci Rep,,,True
fdc71cdcdfa62100451d8dde47fc4d04a6f3c7f9,PMC,Genetic drift of human coronavirus OC43 spike gene during adaptive evolution,http://dx.doi.org/10.1038/srep11451,PMC4476415,26099036,CC BY,"Coronaviruses (CoVs) continuously threaten human health. However, to date, the evolutionary mechanisms that govern CoV strain persistence in human populations have not been fully understood. In this study, we characterized the evolution of the major antigen-spike (S) gene in the most prevalent human coronavirus (HCoV) OC43 using phylogenetic and phylodynamic analysis. Among the five known HCoV-OC43 genotypes (A to E), higher substitution rates and dN/dS values as well as more positive selection sites were detected in the S gene of genotype D, corresponding to the most dominant HCoV epidemic in recent years. Further analysis showed that the majority of substitutions were located in the S1 subunit. Among them, seven positive selection sites were chronologically traced in the temporal evolution routes of genotype D, and six were located around the critical sugar binding region in the N-terminal domain (NTD) of S protein, an important sugar binding domain of CoV. These findings suggest that the genetic drift of the S gene may play an important role in genotype persistence in human populations, providing insights into the mechanisms of HCoV-OC43 adaptive evolution.",2015 Jun 22,"['Ren, Lili', 'Zhang, Yue', 'Li, Jianguo', 'Xiao, Yan', 'Zhang, Jing', 'Wang, Ying', 'Chen, Lan', 'Paranhos-Baccalà, Gláucia', 'Wang, Jianwei']",Sci Rep,,,False
1f91af10bd4371cfb8d9e08a8a1518d8bbd6d4f5,PMC,"Host Subtraction, Filtering and Assembly Validations for Novel Viral Discovery Using Next Generation Sequencing Data",http://dx.doi.org/10.1371/journal.pone.0129059,PMC4476701,26098299,CC BY,"The use of next generation sequencing (NGS) to identify novel viral sequences from eukaryotic tissue samples is challenging. Issues can include the low proportion and copy number of viral reads and the high number of contigs (post-assembly), making subsequent viral analysis difficult. Comparison of assembly algorithms with pre-assembly host-mapping subtraction using a short-read mapping tool, a k-mer frequency based filter and a low complexity filter, has been validated for viral discovery with Illumina data derived from naturally infected liver tissue and simulated data. Assembled contig numbers were significantly reduced (up to 99.97%) by the application of these pre-assembly filtering methods. This approach provides a validated method for maximizing viral contig size as well as reducing the total number of assembled contigs that require down-stream analysis as putative viral nucleic acids.",2015 Jun 22,"['Daly, Gordon M.', 'Leggett, Richard M.', 'Rowe, William', 'Stubbs, Samuel', 'Wilkinson, Maxim', 'Ramirez-Gonzalez, Ricardo H.', 'Caccamo, Mario', 'Bernal, William', 'Heeney, Jonathan L.']",PLoS One,,,True
cf085fe7f16317b15dddc417b76252025fc80f61,PMC,Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis,http://dx.doi.org/10.1038/ncomms8375,PMC4477037,26077231,CC BY,"Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages. In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen. Individual antibodies only partially neutralize GM-CSF activity using an in vitro bioassay, depending on the experimental conditions, while, when injected in mice together with human GM-CSF, they lead to the accumulation of a large pool of circulating GM-CSF that remains partially bioavailable. In contrast, a combination of three non-cross-competing antibodies completely neutralizes GM-CSF activity in vitro by sequestering the cytokine in high-molecular-weight complexes, and in vivo promotes the rapid degradation of GM-CSF-containing immune complexes in an Fc-dependent manner. Taken together, these findings provide a plausible explanation for the severe phenotype of PAP patients and for the safety of treatments based on single anti-GM-CSF monoclonal antibodies.",2015 Jun 16,"['Piccoli, Luca', 'Campo, Ilaria', 'Fregni, Chiara Silacci', 'Rodriguez, Blanca Maria Fernandez', 'Minola, Andrea', 'Sallusto, Federica', 'Luisetti, Maurizio', 'Corti, Davide', 'Lanzavecchia, Antonio']",Nat Commun,,,True
288f6a1df837cdc3cb81ed98a89f6c893ffe0b13,PMC,Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis,http://dx.doi.org/10.1038/ncomms8375,PMC4477037,26077231,CC BY,"Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages. In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen. Individual antibodies only partially neutralize GM-CSF activity using an in vitro bioassay, depending on the experimental conditions, while, when injected in mice together with human GM-CSF, they lead to the accumulation of a large pool of circulating GM-CSF that remains partially bioavailable. In contrast, a combination of three non-cross-competing antibodies completely neutralizes GM-CSF activity in vitro by sequestering the cytokine in high-molecular-weight complexes, and in vivo promotes the rapid degradation of GM-CSF-containing immune complexes in an Fc-dependent manner. Taken together, these findings provide a plausible explanation for the severe phenotype of PAP patients and for the safety of treatments based on single anti-GM-CSF monoclonal antibodies.",2015 Jun 16,"['Piccoli, Luca', 'Campo, Ilaria', 'Fregni, Chiara Silacci', 'Rodriguez, Blanca Maria Fernandez', 'Minola, Andrea', 'Sallusto, Federica', 'Luisetti, Maurizio', 'Corti, Davide', 'Lanzavecchia, Antonio']",Nat Commun,,,False
c831071c9229a681189522e08cfc3b64f84f95db,PMC,Ionizing air affects influenza virus infectivity and prevents airborne-transmission,http://dx.doi.org/10.1038/srep11431,PMC4477231,26101102,CC BY,"By the use of a modified ionizer device we describe effective prevention of airborne transmitted influenza A (strain Panama 99) virus infection between animals and inactivation of virus (>97%). Active ionizer prevented 100% (4/4) of guinea pigs from infection. Moreover, the device effectively captured airborne transmitted calicivirus, rotavirus and influenza virus, with recovery rates up to 21% after 40 min in a 19 m(3) room. The ionizer generates negative ions, rendering airborne particles/aerosol droplets negatively charged and electrostatically attracts them to a positively charged collector plate. Trapped viruses are then identified by reverse transcription quantitative real-time PCR. The device enables unique possibilities for rapid and simple removal of virus from air and offers possibilities to simultaneously identify and prevent airborne transmission of viruses.",2015 Jun 23,"['Hagbom, Marie', 'Nordgren, Johan', 'Nybom, Rolf', 'Hedlund, Kjell-Olof', 'Wigzell, Hans', 'Svensson, Lennart']",Sci Rep,,,True
ed461df407adc47368723e0d97af0d21630e6dde,PMC,N-terminal functional domain of Gasdermin A3 regulates mitochondrial homeostasis via mitochondrial targeting,http://dx.doi.org/10.1186/s12929-015-0152-0,PMC4477613,26100518,CC BY,"BACKGROUND: The epidermis forms a critical barrier that is maintained by orchestrated programs of proliferation, differentiation, and cell death. Gene mutations that disturb this turnover process may cause skin diseases. Human GASDERMIN A (GSDMA) is frequently silenced in gastric cancer cell lines and its overexpression has been reported to induce apoptosis. GSDMA has also been linked with airway hyperresponsiveness in genetic association studies. The function of GSDMA in the skin was deduced by dominant mutations in mouse gasdermin A3 (Gsdma3), which caused skin inflammation and hair loss. However, the mechanism for the autosomal dominance of Gsdma3 mutations and the mode of Gsdma3’s action remain unanswered. RESULTS: We demonstrated a novel function of Gsdma3 in modulating mitochondrial oxidative stress. We showed that Gsdma3 is regulated by intramolecular fold-back inhibition, which is disrupted by dominant mutations in the C-terminal domain. The unmasked N-terminal domain of Gsdma3 associates with Hsp90 and is delivered to mitochondrial via mitochondrial importer receptor Tom70, where it interacts with the mitochondrial chaperone Trap1 and causes increased production of mitochondrial reactive oxygen species (ROS), dissipation of mitochondrial membrane potential, and mitochondrial permeability transition (MPT). Overexpression of the C-terminal domain of Gsdma3 as well as pharmacological interventions of mitochondrial translocation, ROS production, and MPT pore opening alleviate the cell death induced by Gsdma3 mutants. CONCLUSIONS: Our results indicate that the genetic mutations in the C-terminal domain of Gsdma3 are gain-of-function mutations which unmask the N-terminal functional domain of Gsdma3. Gsdma3 regulates mitochondrial oxidative stress through mitochondrial targeting. Since mitochondrial ROS has been shown to promote epidermal differentiation, we hypothesize that Gsdma3 regulates context-dependent response of keratinocytes to differentiation and cell death signals by impinging on mitochondria. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12929-015-0152-0) contains supplementary material, which is available to authorized users.",2015 Jun 24,"['Lin, Pei-Hsuan', 'Lin, Hsien-Yi', 'Kuo, Cheng-Chin', 'Yang, Liang-Tung']",J Biomed Sci,,,False
4565dc1b4397e2959bd9e41cf1b32c37a836f7e9,PMC,N-terminal functional domain of Gasdermin A3 regulates mitochondrial homeostasis via mitochondrial targeting,http://dx.doi.org/10.1186/s12929-015-0152-0,PMC4477613,26100518,CC BY,"BACKGROUND: The epidermis forms a critical barrier that is maintained by orchestrated programs of proliferation, differentiation, and cell death. Gene mutations that disturb this turnover process may cause skin diseases. Human GASDERMIN A (GSDMA) is frequently silenced in gastric cancer cell lines and its overexpression has been reported to induce apoptosis. GSDMA has also been linked with airway hyperresponsiveness in genetic association studies. The function of GSDMA in the skin was deduced by dominant mutations in mouse gasdermin A3 (Gsdma3), which caused skin inflammation and hair loss. However, the mechanism for the autosomal dominance of Gsdma3 mutations and the mode of Gsdma3’s action remain unanswered. RESULTS: We demonstrated a novel function of Gsdma3 in modulating mitochondrial oxidative stress. We showed that Gsdma3 is regulated by intramolecular fold-back inhibition, which is disrupted by dominant mutations in the C-terminal domain. The unmasked N-terminal domain of Gsdma3 associates with Hsp90 and is delivered to mitochondrial via mitochondrial importer receptor Tom70, where it interacts with the mitochondrial chaperone Trap1 and causes increased production of mitochondrial reactive oxygen species (ROS), dissipation of mitochondrial membrane potential, and mitochondrial permeability transition (MPT). Overexpression of the C-terminal domain of Gsdma3 as well as pharmacological interventions of mitochondrial translocation, ROS production, and MPT pore opening alleviate the cell death induced by Gsdma3 mutants. CONCLUSIONS: Our results indicate that the genetic mutations in the C-terminal domain of Gsdma3 are gain-of-function mutations which unmask the N-terminal functional domain of Gsdma3. Gsdma3 regulates mitochondrial oxidative stress through mitochondrial targeting. Since mitochondrial ROS has been shown to promote epidermal differentiation, we hypothesize that Gsdma3 regulates context-dependent response of keratinocytes to differentiation and cell death signals by impinging on mitochondria. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12929-015-0152-0) contains supplementary material, which is available to authorized users.",2015 Jun 24,"['Lin, Pei-Hsuan', 'Lin, Hsien-Yi', 'Kuo, Cheng-Chin', 'Yang, Liang-Tung']",J Biomed Sci,,,False
5f658c058c7877ad7df3f02da1ee3593b60e4429,PMC,N-terminal functional domain of Gasdermin A3 regulates mitochondrial homeostasis via mitochondrial targeting,http://dx.doi.org/10.1186/s12929-015-0152-0,PMC4477613,26100518,CC BY,"BACKGROUND: The epidermis forms a critical barrier that is maintained by orchestrated programs of proliferation, differentiation, and cell death. Gene mutations that disturb this turnover process may cause skin diseases. Human GASDERMIN A (GSDMA) is frequently silenced in gastric cancer cell lines and its overexpression has been reported to induce apoptosis. GSDMA has also been linked with airway hyperresponsiveness in genetic association studies. The function of GSDMA in the skin was deduced by dominant mutations in mouse gasdermin A3 (Gsdma3), which caused skin inflammation and hair loss. However, the mechanism for the autosomal dominance of Gsdma3 mutations and the mode of Gsdma3’s action remain unanswered. RESULTS: We demonstrated a novel function of Gsdma3 in modulating mitochondrial oxidative stress. We showed that Gsdma3 is regulated by intramolecular fold-back inhibition, which is disrupted by dominant mutations in the C-terminal domain. The unmasked N-terminal domain of Gsdma3 associates with Hsp90 and is delivered to mitochondrial via mitochondrial importer receptor Tom70, where it interacts with the mitochondrial chaperone Trap1 and causes increased production of mitochondrial reactive oxygen species (ROS), dissipation of mitochondrial membrane potential, and mitochondrial permeability transition (MPT). Overexpression of the C-terminal domain of Gsdma3 as well as pharmacological interventions of mitochondrial translocation, ROS production, and MPT pore opening alleviate the cell death induced by Gsdma3 mutants. CONCLUSIONS: Our results indicate that the genetic mutations in the C-terminal domain of Gsdma3 are gain-of-function mutations which unmask the N-terminal functional domain of Gsdma3. Gsdma3 regulates mitochondrial oxidative stress through mitochondrial targeting. Since mitochondrial ROS has been shown to promote epidermal differentiation, we hypothesize that Gsdma3 regulates context-dependent response of keratinocytes to differentiation and cell death signals by impinging on mitochondria. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12929-015-0152-0) contains supplementary material, which is available to authorized users.",2015 Jun 24,"['Lin, Pei-Hsuan', 'Lin, Hsien-Yi', 'Kuo, Cheng-Chin', 'Yang, Liang-Tung']",J Biomed Sci,,,False
ffd291065f3e320c4d8417a78d61116f3a919fae,PMC,N-terminal functional domain of Gasdermin A3 regulates mitochondrial homeostasis via mitochondrial targeting,http://dx.doi.org/10.1186/s12929-015-0152-0,PMC4477613,26100518,CC BY,"BACKGROUND: The epidermis forms a critical barrier that is maintained by orchestrated programs of proliferation, differentiation, and cell death. Gene mutations that disturb this turnover process may cause skin diseases. Human GASDERMIN A (GSDMA) is frequently silenced in gastric cancer cell lines and its overexpression has been reported to induce apoptosis. GSDMA has also been linked with airway hyperresponsiveness in genetic association studies. The function of GSDMA in the skin was deduced by dominant mutations in mouse gasdermin A3 (Gsdma3), which caused skin inflammation and hair loss. However, the mechanism for the autosomal dominance of Gsdma3 mutations and the mode of Gsdma3’s action remain unanswered. RESULTS: We demonstrated a novel function of Gsdma3 in modulating mitochondrial oxidative stress. We showed that Gsdma3 is regulated by intramolecular fold-back inhibition, which is disrupted by dominant mutations in the C-terminal domain. The unmasked N-terminal domain of Gsdma3 associates with Hsp90 and is delivered to mitochondrial via mitochondrial importer receptor Tom70, where it interacts with the mitochondrial chaperone Trap1 and causes increased production of mitochondrial reactive oxygen species (ROS), dissipation of mitochondrial membrane potential, and mitochondrial permeability transition (MPT). Overexpression of the C-terminal domain of Gsdma3 as well as pharmacological interventions of mitochondrial translocation, ROS production, and MPT pore opening alleviate the cell death induced by Gsdma3 mutants. CONCLUSIONS: Our results indicate that the genetic mutations in the C-terminal domain of Gsdma3 are gain-of-function mutations which unmask the N-terminal functional domain of Gsdma3. Gsdma3 regulates mitochondrial oxidative stress through mitochondrial targeting. Since mitochondrial ROS has been shown to promote epidermal differentiation, we hypothesize that Gsdma3 regulates context-dependent response of keratinocytes to differentiation and cell death signals by impinging on mitochondria. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12929-015-0152-0) contains supplementary material, which is available to authorized users.",2015 Jun 24,"['Lin, Pei-Hsuan', 'Lin, Hsien-Yi', 'Kuo, Cheng-Chin', 'Yang, Liang-Tung']",J Biomed Sci,,,False
32d5699f514f8d58fa7939fefaea6ef9fce1121c,PMC,N-terminal functional domain of Gasdermin A3 regulates mitochondrial homeostasis via mitochondrial targeting,http://dx.doi.org/10.1186/s12929-015-0152-0,PMC4477613,26100518,CC BY,"BACKGROUND: The epidermis forms a critical barrier that is maintained by orchestrated programs of proliferation, differentiation, and cell death. Gene mutations that disturb this turnover process may cause skin diseases. Human GASDERMIN A (GSDMA) is frequently silenced in gastric cancer cell lines and its overexpression has been reported to induce apoptosis. GSDMA has also been linked with airway hyperresponsiveness in genetic association studies. The function of GSDMA in the skin was deduced by dominant mutations in mouse gasdermin A3 (Gsdma3), which caused skin inflammation and hair loss. However, the mechanism for the autosomal dominance of Gsdma3 mutations and the mode of Gsdma3’s action remain unanswered. RESULTS: We demonstrated a novel function of Gsdma3 in modulating mitochondrial oxidative stress. We showed that Gsdma3 is regulated by intramolecular fold-back inhibition, which is disrupted by dominant mutations in the C-terminal domain. The unmasked N-terminal domain of Gsdma3 associates with Hsp90 and is delivered to mitochondrial via mitochondrial importer receptor Tom70, where it interacts with the mitochondrial chaperone Trap1 and causes increased production of mitochondrial reactive oxygen species (ROS), dissipation of mitochondrial membrane potential, and mitochondrial permeability transition (MPT). Overexpression of the C-terminal domain of Gsdma3 as well as pharmacological interventions of mitochondrial translocation, ROS production, and MPT pore opening alleviate the cell death induced by Gsdma3 mutants. CONCLUSIONS: Our results indicate that the genetic mutations in the C-terminal domain of Gsdma3 are gain-of-function mutations which unmask the N-terminal functional domain of Gsdma3. Gsdma3 regulates mitochondrial oxidative stress through mitochondrial targeting. Since mitochondrial ROS has been shown to promote epidermal differentiation, we hypothesize that Gsdma3 regulates context-dependent response of keratinocytes to differentiation and cell death signals by impinging on mitochondria. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12929-015-0152-0) contains supplementary material, which is available to authorized users.",2015 Jun 24,"['Lin, Pei-Hsuan', 'Lin, Hsien-Yi', 'Kuo, Cheng-Chin', 'Yang, Liang-Tung']",J Biomed Sci,,,True
b3ad716630b356b1399e9df08cad73b1e92f317d,PMC,"Changing risk awareness and personal protection measures for low to high pathogenic avian influenza in live-poultry markets in Taiwan, 2007 to 2012",http://dx.doi.org/10.1186/s12879-015-0987-8,PMC4478710,26104109,CC BY,"BACKGROUND: Outbreaks of low and high pathogenic avian influenza (LPAI, HPAI) H5N2 in chickens have occurred in Taiwan since 2003 and 2012, respectively. Fully understanding the different awareness, attitudes and protective behaviors adopted by workers in live-poultry markets (LPMWs) and local community residents (CRs) to face the challenges of LPAI and HPAI is very important to minimize viral adaptations to human populations. METHODS: A structural questionnaire containing information on respondents’ occupation, personal risk awareness, attitudes toward different policies, and preventative measures was administered. The two-stage survey (before and after HPAI H5N2 outbreaks) was conducted from 2007 to 2012, including: (1) 430 LPMWs and 418 CRs at LPMs from different geographical areas of Taiwan after the government announced outbreaks of LPAI H5N2 during 2007–2009, and (2) 73 LPMWs and 152 CRs at two LPMs in central Taiwan after the HPAI H5N2 outbreaks in 2012. The chi-squared test and logistic regression were applied for univariate and multivariate analyses, respectively. RESULTS: Before HPAI-H5N2 outbreaks, higher educated respondents demonstrated greater risk awareness and concerns regarding AI. However, LPM-workers protected themselves less from AI viruses (AIVs) and had lower acceptance of human or avian influenza vaccines. Most importantly, the participants who opposed (versus agreed with) the policy on banning live-poultry slaughtering at LPMs reported lower awareness of government prevention and control policies [Odds Ratio (OR): 0.76, 95 % Confidence Interval (CI): 0.56–1.01] or practiced preventive measures (OR: 0.42, 95 % CI: 0.25–0.70). After HPAI-H5N2 outbreaks, the risk awareness about AI in central Taiwan significantly increased [LPAI to HPAI LPMWs: 34.6 to 65.6 %, p < 0.05; CRs: 44.0 to 76.5 %, p < 0.05] and LPMWs’ belief in the effectiveness of vaccination to prevent human or avian influenza virus infection strikingly decreased (92.3 to 68.5 %, p < 0.05). CONCLUSIONS: Risk awareness depends on high or low pathogenicity of AIVs, working in LPMs, levels of education, age, and proximity to the sites of severe AI outbreaks. Regardless of novel LPAI or HPAI virus reassortants that pose public health risks, prompt and clear risk communication focusing on both correct information about AIVs and the most appropriate preventive measures are important for effective prevention of human infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0987-8) contains supplementary material, which is available to authorized users.",2015 Jun 24,"['Liu, Ming-Der', 'Chan, Ta-Chien', 'Wan, Cho-Hua', 'Lin, Hsiu-Ping', 'Tung, Tsung-Hua', 'Hu, Fu-Chang', 'King, Chwan-Chuen']",BMC Infect Dis,,,True
933e9eb0d544bb5afe34f6d6049b4c8bc5e96d19,PMC,"Prevalence of respiratory virus in symptomatic children in private physician office settings in five communities of the state of Veracruz, Mexico",http://dx.doi.org/10.1186/s13104-015-1239-0,PMC4479372,26108920,CC BY,"BACKGROUND: Acute respiratory tract infections are the leading cause of morbidity and mortality in children worldwide. Many studies have described the frequency of viruses in hospitalized patients, but studies describing the prevalence of viruses in the community setting are limited, particularly in developing countries, where most of the deaths from serious respiratory diseases occur. The aim of this study was to evaluate the diversity of respiratory viruses in the community setting using molecular diagnostic tools, as well as the clinical characteristics of respiratory viral infections in the general pediatric practice in Mexico. METHODS: Children with respiratory tract infections attending private pediatric practices during a 10-month period in five cities of the state of Veracruz were included. Nasal swabs were taken and processed by a multiplex detection kit for 15 respiratory viruses. RESULTS: 525 children were included from July 2011 to May 2012; 44% were female, mean age was 45 months. The 3 most frequent clinical diagnosis were: rhinopharyngitis 68%, pharyngitis 18%, and 3.3% influenza-like illness. 71.5% of the samples were positive for virus. The five most frequent pathogens were respiratory syncycitial virus in 18.3% of the children, rhinovirus in 17.5%, influenza A 9.1%, adenovirus 7.2%, and enterovirus 3.4%, although all 15 viruses were detected; there were viral coinfections in 14.1%, and 28.5% of the samples were negative. CONCLUSIONS: A large proportion of respiratory infections in the community setting in Mexico was associated to viruses. Although testing for common respiratory pathogens in children with acute respiratory tract infections may lead to a better understanding of the role of viral pathogens in, and eventually to improvement in the management of, individual patients, additional prospective studies are required to study the need of routinely using such tests in general pediatric practices in resource-limited countries.",2015 Jun 25,"['Wong-Chew, Rosa M', 'Espinoza, Marco A', 'Taboada, Blanca', 'Aponte, Fernando E', 'Arias-Ortiz, María A', 'Monge-Martínez, Jesús', 'Rodríguez-Vázquez, Rubén', 'Díaz-Hernández, Fidel', 'Zárate-Vidal, Fernando', 'Santos-Preciado, José I', 'López, Susana', 'Arias, Carlos F']",BMC Res Notes,,,True
44d9ad484dc917e82daa41c802c2157d3f20dda4,PMC,Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination,http://dx.doi.org/10.1186/s13578-015-0025-y,PMC4480891,26113972,CC BY,"BACKGROUND: DNA vaccines have emerged as attractive candidates for the control of human papillomavirus (HPV)-associated malignancies. However, DNA vaccines suffer from limited immunogenicity and thus strategies to enhance DNA vaccine potency are needed. We have previously demonstrated that for DNA vaccines encoding HPV-16 E7 antigen (CRT/E7) linkage with calreticulin (CRT) linked enhances both the E7-specific CD8(+) T cell immune responses and antitumor effects against E7-expressing tumors. In the current study, we aim to introduce an approach to elicit potent CD4(+) T cell help for the enhancement of antigen-specific CD8(+) T cell immune responses generated by CRT/E7 DNA vaccination by using co-administration of a DNA vector expressing papillomavirus major and minor capsid antigens, L1 and L2. RESULT: We showed that co-administration of vectors containing codon-optimized bovine papillomavirus type 1 (BPV-1) L1 and L2 in combination with DNA vaccines could elicit enhanced antigen-specific CD8(+) in both CRT/E7 and ovalbumin (OVA) antigenic systems. We also demonstrated that co-administration of vectors expressing BPV-1 L1 and/or L2 DNA with CRT/E7 DNA led to the generation of L1/L2-specific CD4(+) T cell immune responses and L1-specific neutralizing antibodies. Furthermore, we showed that co-administration with DNA encoding BPV1 L1 significantly enhances the therapeutic antitumor effects generated by CRT/E7 DNA vaccination. In addition, the observed enhancement of CD8(+) T cell immune responses by DNA encoding L1 and L2 was also found to extend to HPV-16 L1/L2 system. CONCLUSION: Our strategy elicits both potent neutralizing antibody and therapeutic responses and may potentially be extended to other antigenic systems beyond papillomavirus for the control of infection and/or cancer.",2015 Jun 25,"['Yang, Benjamin', 'Yang, Andrew', 'Peng, Shiwen', 'Pang, Xiaowu', 'Roden, Richard B.S.', 'Wu, T.-C.', 'Hung, Chien-Fu']",Cell Biosci,,,True
00ae0041374cbbf28df0d2cbeb08c1396a4f7878,PMC,Enzyme assays for synthesis and degradation of 2-5As and other 2′-5′ oligonucleotides,http://dx.doi.org/10.1186/s12858-015-0043-8,PMC4481073,26113370,CC BY,"BACKGROUND: The 5′-triphosphorylated, 2′-5′-linked oligoadenylate polyribonucleotides (2-5As) are central to the interferon-induced antiviral 2-5A system. The 2-5As bind and activate the RNase L, an endoRNase degrading viral and cellular RNA leading to inhibition of viral replication. The 2-5A system is tightly controlled by synthesis and degradation of 2-5As. Whereas synthesis is mediated by the 2′-5′ oligoadenylate synthetase family of enzymes, degradation seems to be orchestrated by multiple enzyme nucleases including phosphodiesterase 12, the ectonucleotide pyrophosphatase/phosphodiesterase 1 and the A-kinase anchoring protein 7. RESULTS: Here we present assay tools for identification and characterization of the enzymes regulating cellular 2-5A levels. A procedure is described for the production of 2′-5′ oligoadenylates, which are then used as substrates for development and demonstration of enzyme assays measuring synthetase and nuclease activities, respectively. The synthetase assays produce only a single reaction product allowing for very precise kinetic assessment of the enzymes. We present an assay using dATP and the A(pA)(3) tetramer core as substrates, which requires prior isolation of A(pA)(3). A synthetase assay using either of the dNTPs individually together with NAD(+) as substrates is also presented. The nuclease reactions make use of the isolated 2′-5′ oligoadenylates in producing a mixture of shorter reaction products, which are resolved by ion-exchange chromatography to determine the enzyme activities. A purified human 2′-5′ oligoadenylate synthetase and a purified human phosphodiesterase 12 along with crude extracts expressing those proteins, are used to demonstrate the assays. CONCLUSIONS: This paper comprises an assay toolbox for identification and characterization of the synthetases and nucleases regulating cellular 2-5A levels. Assays are presented for both enzyme families. The assays can also be used to address a broader cellular role of the OAS enzymes, based on the multiple substrate specificity intrinsic to these proteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12858-015-0043-8) contains supplementary material, which is available to authorized users.",2015 Jun 26,"['Poulsen, Jesper Buchhave', 'Kjær, Karina Hansen', 'Justesen, Just', 'Martensen, Pia Møller']",BMC Biochem,,,True
5a575cf8c90efa9e40cfbf87f2a202bb39d68951,PMC,Evaluation of Four Commercial Multiplex Molecular Tests for the Diagnosis of Acute Respiratory Infections,http://dx.doi.org/10.1371/journal.pone.0130378,PMC4481272,26107509,CC BY,"Acute Respiratory Infections (ARIs) are responsible for considerable morbidity and mortality worldwide. Documentation of respiratory specimens can help for an appropriate clinical management with a significant effect on the disease progress in patient, the antimicrobial therapy used and the risk of secondary spread of infection. Here, we compared the performances of four commercial multiplex kits used in French University Hospital diagnostic microbiology laboratories for the detection of ARI pathogens (i.e., the xTAG Respiratory Viral Panel Fast, RespiFinder SMART 22, CLART PneumoVir and Fast Track Diagnostics Respiratory Pathogen 33 kits). We used a standardised nucleic acids extraction protocol and a comprehensive comparative approach that mixed reference to well established real-time PCR detection techniques and analysis of convergent positive results. We tested 166 respiratory clinical samples and identified a global high degree of correlation for at least three of the techniques (xTAG, RespiFinder and FTD33). For these techniques, the highest Youden’s index (YI), positive predictive (PPV) and specificity (Sp) values were observed for Core tests (e.g., influenza A [YI:0.86–1.00; PPV:78.95–100.00; Sp:97.32–100.00] & B [YI:0.44–1.00; PPV:100.00; Sp:100.00], hRSV [YI:0.50–0.99; PPV:85.71–100.00; Sp:99.38–100.00], hMPV [YI:0.71–1.00; PPV:83.33–100.00; Sp:99.37–100.00], EV/hRV [YI:0.62–0.82; PPV:93.33–100.00; Sp:94.48–100.00], AdV [YI:1.00; PPV:100.00; Sp:100.00] and hBoV [YI:0.20–0.80; PPV:57.14–100.00; Sp:98.14–100.00]). The present study completed an overview of the multiplex techniques available for the diagnosis of acute respiratory infections.",2015 Jun 24,"['Salez, Nicolas', 'Vabret, Astrid', 'Leruez-Ville, Marianne', 'Andreoletti, Laurent', 'Carrat, Fabrice', 'Renois, Fanny', 'de Lamballerie, Xavier']",PLoS One,,,True
334adcddbb251335c86c3a5d79a0f66b526109ff,PMC,Complete Genome Sequences of Two Genetically Distinct Variants of Porcine Epidemic Diarrhea Virus in the Eastern Region of Thailand,http://dx.doi.org/10.1128/genomeA.00634-15,PMC4481281,26112783,CC BY,"Porcine epidemic diarrhea virus (PEDV) has continued to cause sporadic outbreaks in Thailand since 2007. Previously, PEDV in Thailand was a new variant containing an insertion and deletion in the spike gene. Herein, full-length genome sequences are reported for two variants of PEDV isolates from pigs displaying diarrhea in Thailand.",2015 Jun 25,"['Cheun-Arom, Thaniwan', 'Temeeyasen, Gun', 'Srijangwad, Anchalee', 'Tripipat, Thitima', 'Sangmalee, Suphattra', 'Vui, Dam Thi', 'Chuanasa, Taksina', 'Tantituvanont, Angkana', 'Nilubol, Dachrit']",Genome Announc,,,True
ccc32d31656760db245b5cd683d144eb013624c3,PMC,Experimental African Trypanosome Infection by Needle Passage or Natural Tsetse Fly Challenge Thwarts the Development of Collagen-Induced Arthritis in DBA/1 Prone Mice via an Impairment of Antigen Specific B Cell Autoantibody Titers,http://dx.doi.org/10.1371/journal.pone.0130431,PMC4482398,26110416,CC BY,"Collagen-induced arthritis is a B cell-mediated autoimmune disease. Recently published studies have demonstrated that in some rare cases pathogens can confer protection from autoimmunity. Trypanosoma brucei parasites are tsetse fly transmitted extracellular protozoans causing sleeping sickness disease in humans and Nagana in livestock in sub-Saharan endemic areas. In the past, we demonstrated that trypanosome infections impair B cell homeostasis and abolish vaccine-induced protection against unrelated antigens. Hence, here we hypothesized that trypanosome infection can affect the onset of CIA by specifically dampening specific B-cell responses and type II collagen antibody titers in DBA/1 prone mice. We observed a substantial delay in the onset of collagen-induced arthritis in T. brucei-infected DBA/1 mice that correlates with a drastic decrease of type II collagen titers of the different IgG isotypes in the serum. Treatment of infected mice with Berenil, a trypanocidal drug, restored the development of CIA-associated clinical symptoms. Interestingly, these data were confirmed by the challenge of immunized DBA/1 prone mice with T. brucei-infected tsetse flies. Together, these results demonstrate that T. brucei infection is impairing the maintenance of the antigen specific plasma B cell pool driving the development of CIA in DBA/1 prone mice.",2015 Jun 25,"['De Trez, Carl', 'Katsandegwaza, Brunette', 'Caljon, Guy', 'Magez, Stefan']",PLoS One,,,True
0fbc383f838f9db0f9146ae8889373a9375ec056,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,True
deabc76cd9ee100c9a4088508bdad5048dc8c839,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,False
c117f1615a020ad82318becdf8f709f52aeb2efd,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,False
feca5c689581defdc70a39704fc1ef8bdb4189c8,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,False
2eaa56f8da9327aa9ed79a7eea423bf116d20117,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,False
1c1a77f8a0e0befc562a31b44721256478a5fc9e,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,False
c6d54cceed065d505890921bd3936410b4134c3f,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,False
98250784b8bce843095839979513899ff18edf9a,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,False
424606001b632c4148c73e7a2c288a08ff978842,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,True
84c1fe63d284751ee5ff158c8dd19d190f90f541,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,False
57cffb9026a4e37031021f91832d48c79df0fd75,PMC,New Metrics for Evaluating Viral Respiratory Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0131451,PMC4482571,26115403,CC BY,"Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.",2015 Jun 26,"['Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Baric, Ralph S.', 'Ferris, Martin T.']",PLoS One,,,True
e82c458779137caddb713da94ff08b30a1f32b9f,PMC,New Metrics for Evaluating Viral Respiratory Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0131451,PMC4482571,26115403,CC BY,"Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.",2015 Jun 26,"['Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Baric, Ralph S.', 'Ferris, Martin T.']",PLoS One,,,False
5f62bfe3cf650294a86bbf7350cc918f82ec4419,PMC,New Metrics for Evaluating Viral Respiratory Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0131451,PMC4482571,26115403,CC BY,"Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.",2015 Jun 26,"['Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Baric, Ralph S.', 'Ferris, Martin T.']",PLoS One,,,False
8dc531b6289f49c6a17ead3a723e71c2cd34e4f2,PMC,New Metrics for Evaluating Viral Respiratory Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0131451,PMC4482571,26115403,CC BY,"Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.",2015 Jun 26,"['Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Baric, Ralph S.', 'Ferris, Martin T.']",PLoS One,,,False
132ebff69dbef71f408ae161b8ebd53de0f2c9f4,PMC,New Metrics for Evaluating Viral Respiratory Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0131451,PMC4482571,26115403,CC BY,"Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.",2015 Jun 26,"['Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Baric, Ralph S.', 'Ferris, Martin T.']",PLoS One,,,False
67a8a9fcd94c110d8b738ee67328bd76d73fd30c,PMC,New Metrics for Evaluating Viral Respiratory Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0131451,PMC4482571,26115403,CC BY,"Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.",2015 Jun 26,"['Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Baric, Ralph S.', 'Ferris, Martin T.']",PLoS One,,,False
1015f9908a0ba0202d9aa3be842f51fd696be62f,PMC,New Metrics for Evaluating Viral Respiratory Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0131451,PMC4482571,26115403,CC BY,"Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.",2015 Jun 26,"['Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Baric, Ralph S.', 'Ferris, Martin T.']",PLoS One,,,False
b8efd7ebd2057d44c6544e918c3631ac395c7fb2,PMC,Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs,http://dx.doi.org/10.1371/journal.ppat.1005016,PMC4482612,26115029,CC0,"The filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade. Antibodies against the filovirus surface glycoprotein (GP) have been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific. Many monoclonal antibodies (mAbs) have been described against Ebola virus. In contrast, relatively few have been described against Marburg virus. Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. The most efficacious mAbs in this panel were found to recognize a novel “wing” feature on the GP2 subunit that is unique to Marburg and does not exist in Ebola. Two of these anti-wing antibodies confer 90 and 100% protection, respectively, one hour post-exposure in mice challenged with MARV.",2015 Jun 26,"['Fusco, Marnie L.', 'Hashiguchi, Takao', 'Cassan, Robyn', 'Biggins, Julia E.', 'Murin, Charles D.', 'Warfield, Kelly L.', 'Li, Sheng', 'Holtsberg, Frederick W.', 'Shulenin, Sergey', 'Vu, Hong', 'Olinger, Gene G.', 'Kim, Do H.', 'Whaley, Kevin J.', 'Zeitlin, Larry', 'Ward, Andrew B.', 'Nykiforuk, Cory', 'Aman, M. Javad', 'Berry, Jody', 'Saphire, Erica Ollmann']",PLoS Pathog,,,True
77b8307c0de7ad71378665456b43e4185d5e5477,PMC,Economic Assessment of FMDv Releases from the National Bio and Agro Defense Facility,http://dx.doi.org/10.1371/journal.pone.0129134,PMC4482686,26114546,CC BY,"This study evaluates the economic consequences of hypothetical foot-and-mouth disease releases from the future National Bio and Agro Defense Facility in Manhattan, Kansas. Using an economic framework that estimates the impacts to agricultural firms and consumers, quantifies costs to non-agricultural activities in the epidemiologically impacted region, and assesses costs of response to the government, we find the distribution of economic impacts to be very significant. Furthermore, agricultural firms and consumers bear most of the impacts followed by the government and the regional non-agricultural firms.",2015 Jun 26,"['Pendell, Dustin L.', 'Marsh, Thomas L.', 'Coble, Keith H.', 'Lusk, Jayson L.', 'Szmania, Sara C.']",PLoS One,,,True
389b75fa8272ae7d2ab3d90ae8c1edbdf55c0463,PMC,Sequence-Specific Fidelity Alterations Associated with West Nile Virus Attenuation in Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1005009,PMC4482725,26114757,CC BY,"High rates of error-prone replication result in the rapid accumulation of genetic diversity of RNA viruses. Recent studies suggest that mutation rates are selected for optimal viral fitness and that modest variations in replicase fidelity may be associated with viral attenuation. Arthropod-borne viruses (arboviruses) are unique in their requirement for host cycling and may necessitate substantial genetic and phenotypic plasticity. In order to more thoroughly investigate the correlates, mechanisms and consequences of arbovirus fidelity, we selected fidelity variants of West Nile virus (WNV; Flaviviridae, Flavivirus) utilizing selection in the presence of a mutagen. We identified two mutations in the WNV RNA-dependent RNA polymerase associated with increased fidelity, V793I and G806R, and a single mutation in the WNV methyltransferase, T248I, associated with decreased fidelity. Both deep-sequencing and in vitro biochemical assays confirmed strain-specific differences in both fidelity and mutational bias. WNV fidelity variants demonstrated host-specific alterations to replicative fitness in vitro, with modest attenuation in mosquito but not vertebrate cell culture. Experimental infections of colonized and field populations of Cx. quinquefaciatus demonstrated that WNV fidelity alterations are associated with a significantly impaired capacity to establish viable infections in mosquitoes. Taken together, these studies (i) demonstrate the importance of allosteric interactions in regulating mutation rates, (ii) establish that mutational spectra can be both sequence and strain-dependent, and (iii) display the profound phenotypic consequences associated with altered replication complex function of flaviviruses.",2015 Jun 26,"['Van Slyke, Greta A.', 'Arnold, Jamie J.', 'Lugo, Alex J.', 'Griesemer, Sara B.', 'Moustafa, Ibrahim M.', 'Kramer, Laura D.', 'Cameron, Craig E.', 'Ciota, Alexander T.']",PLoS Pathog,,,True
1b2079db92924c2ee758d437394789b4822d0327,PMC,"Temporal Trends of In-Hospital Mortality in Patients Treated with Intra-Aortic Balloon Pumping: A Nationwide Population Study in Taiwan, 1998-2008",http://dx.doi.org/10.1371/journal.pone.0131575,PMC4483178,26115413,CC BY,"Intra-aortic balloon pumping (IABP) is widely used for hemodynamic support in critical patients with cardiogenic shock (CS). We examined whether the in-hospital mortality of patients in Taiwan treated with IABP has recently declined. We used Taiwan’s National Health Insurance Research Database to retrospectively review the in-hospital all-cause mortality of 9952 (7146 men [71.8%]) 18-year-old and older patients treated with IABP between 1998 and 2008. The mortality rate was 13.84% (n = 1377). The urbanization levels of the hospitals, and the number of days in the intensive care unit, of hospitalization, and of IABP treatment, and prior percutaneous coronary intervention (PCI) were associated with mortality. Seven thousand six hundred thirty-five patients (76.72%) underwent coronary artery bypass grafting (CABG) surgery, and 576 (5.79%) underwent high-risk PCI with IABP treatment. The number of patients treated with IABP significantly increased during this decade (p(trend) < 0.0001), the in-hospital all-cause mortality for patients treated with IABP significantly decreased (p(trend) = 0.0243), but the in-hospital all-cause mortality of patients who underwent CABG and PCI plus IABP did not decrease. In conclusion, the in-hospital mortality rate of IABP treatment decreased annually in Taiwan during the study period. However, high-risk patients who underwent coronary revascularization with IABP had a higher and unstable in-hospital mortality rate.",2015 Jun 26,"['Ho, Chung-Han', 'Chen, Zhih-Cherng', 'Chu, Chin-Chen', 'Wang, Jhi-Joung', 'Chiang, Chun-Yen']",PLoS One,,,True
4e83f87fdf5b15fb7962c1b6235b520817924a9b,PMC,Entry Inhibition of Influenza Viruses with High Mannose Binding Lectin ESA-2 from the Red Alga Eucheuma serra through the Recognition of Viral Hemagglutinin,http://dx.doi.org/10.3390/md13063454,PMC4483639,26035023,CC BY,"Lectin sensitivity of the recent pandemic influenza A virus (H1N1-2009) was screened for 12 lectins with various carbohydrate specificity by a neutral red dye uptake assay with MDCK cells. Among them, a high mannose (HM)-binding anti-HIV lectin, ESA-2 from the red alga Eucheuma serra, showed the highest inhibition against infection with an EC(50) of 12.4 nM. Moreover, ESA-2 exhibited a wide range of antiviral spectrum against various influenza strains with EC(50)s of pico molar to low nanomolar levels. Besides ESA-2, HM-binding plant lectin ConA, fucose-binding lectins such as fungal AOL from Aspergillus oryzae and AAL from Aleuria aurantia were active against H1N1-2009, but the potency of inhibition was of less magnitude compared with ESA-2. Direct interaction between ESA-2 and a viral envelope glycoprotein, hemagglutinin (HA), was demonstrated by ELISA assay. This interaction was effectively suppressed by glycoproteins bearing HM-glycans, indicating that ESA-2 binds to the HA of influenza virus through HM-glycans. Upon treatment with ESA-2, no viral antigens were detected in the host cells, indicating that ESA-2 inhibited the initial steps of virus entry into the cells. ESA-2 would thus be useful as a novel microbicide to prevent penetration of viruses such as HIV and influenza viruses to the host cells.",2015 May 29,"['Sato, Yuichiro', 'Morimoto, Kinjiro', 'Kubo, Takanori', 'Sakaguchi, Takemasa', 'Nishizono, Akira', 'Hirayama, Makoto', 'Hori, Kanji']",Mar Drugs,,,True
c7f5828ffb5dbc51bda8427bc64056b6eeb1afb0,PMC,Immunological Response to Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex: An RNA-Sequence Analysis of the Bronchial Lymph Node Transcriptome,http://dx.doi.org/10.1371/journal.pone.0131459,PMC4484807,26121276,CC BY,"Susceptibility to bovine respiratory disease (BRD) is multi-factorial and is influenced by stress in conjunction with infection by both bacterial and viral pathogens. While vaccination is broadly used in an effort to prevent BRD, it is far from being fully protective and cases diagnosed from a combination of observed clinical signs without any attempt at identifying the causal pathogens are usually treated with antibiotics. Dairy and beef cattle losses from BRD are profound worldwide and genetic studies have now been initiated to elucidate host loci which underlie susceptibility with the objective of enabling molecular breeding to reduce disease prevalence. In this study, we employed RNA sequencing to examine the bronchial lymph node transcriptomes of controls and beef cattle which had individually been experimentally challenged with bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Pasteurella multocida, Mannheimia haemolytica or Mycoplasma bovis to identify the genes that are involved in the bovine immune response to infection. We found that 142 differentially expressed genes were located in previously described quantitative trait locus regions associated with risk of BRD. Mutations affecting the expression or amino acid composition of these genes may affect disease susceptibility and could be incorporated into molecular breeding programs. Genes involved in innate immunity were generally found to be differentially expressed between the control and pathogen-challenged animals suggesting that variation in these genes may lead to a heritability of susceptibility that is pathogen independent. However, we also found pathogen-specific expression profiles which suggest that host genetic variation for BRD susceptibility is pathogen dependent.",2015 Jun 29,"['Tizioto, Polyana C.', 'Kim, JaeWoo', 'Seabury, Christopher M.', 'Schnabel, Robert D.', 'Gershwin, Laurel J.', 'Van Eenennaam, Alison L.', 'Toaff-Rosenstein, Rachel', 'Neibergs, Holly L.', None, 'Taylor, Jeremy F.']",PLoS One,,,True
974446ae540829dc1b4c7ce8ea1b8dd3843fb3dc,PMC,Specificity and Strain-Typing Capabilities of Nanorod Array-Surface Enhanced Raman Spectroscopy for Mycoplasma pneumoniae Detection,http://dx.doi.org/10.1371/journal.pone.0131831,PMC4487258,26121242,CC0,"Mycoplasma pneumoniae is a cell wall-less bacterial pathogen of the human respiratory tract that accounts for > 20% of all community-acquired pneumonia (CAP). At present the most effective means for detection and strain-typing is quantitative polymerase chain reaction (qPCR), which can exhibit excellent sensitivity and specificity but requires separate tests for detection and genotyping, lacks standardization between available tests and between labs, and has limited practicality for widespread, point-of-care use. We have developed and previously described a silver nanorod array-surface enhanced Raman Spectroscopy (NA-SERS) biosensing platform capable of detecting M. pneumoniae with statistically significant specificity and sensitivity in simulated and true clinical throat swab samples, and the ability to distinguish between reference strains of the two main genotypes of M. pneumoniae. Furthermore, we have established a qualitative lower endpoint of detection for NA-SERS of < 1 genome equivalent (cell/μl) and a quantitative multivariate detection limit of 5.3 ± 1 cells/μl. Here we demonstrate using partial least squares- discriminatory analysis (PLS-DA) of sample spectra that NA-SERS correctly identified M. pneumoniae clinical isolates from globally diverse origins and distinguished these from a panel of 12 other human commensal and pathogenic mycoplasma species with 100% cross-validated statistical accuracy. Furthermore, PLS-DA correctly classified by strain type all 30 clinical isolates with 96% cross-validated accuracy for type 1 strains, 98% cross-validated accuracy for type 2 strains, and 90% cross-validated accuracy for type 2V strains.",2015 Jun 29,"['Henderson, Kelley C.', 'Benitez, Alvaro J.', 'Ratliff, Amy E.', 'Crabb, Donna M.', 'Sheppard, Edward S.', 'Winchell, Jonas M.', 'Dluhy, Richard A.', 'Waites, Ken B.', 'Atkinson, T. Prescott', 'Krause, Duncan C.']",PLoS One,,,True
5688011525aeb581afabe204b64d4da24257aff1,PMC,Emergence of porcine epidemic diarrhea virus in southern Germany,http://dx.doi.org/10.1186/s12917-015-0454-1,PMC4487554,26135732,CC BY,"BACKGROUND: Over the last years, porcine epidemic diarrhea virus (PEDV) has caused devastating enteric diseases in the US and several countries in Asia, while outbreaks in Europe have only been reported sporadically since the 1980s. At present, only insufficient information is available on currently circulating PEDV strains in Europe and their impact on the European swine industry. In this case report, we present epidemic outbreaks of porcine epidemic diarrhea in three farms in South-Western Germany. CASE PRESENTATION: Epidemic outbreaks of diarrhea affecting pigs of all age groups were reported in three farms, one fattening farm and two piglet producing farms, in South-Western Germany between May and November 2014. In the fattening farm yellowish, watery diarrhea without evidence of mucus or blood was associated with a massive reduction of feed consumption. Severity of clinical signs and mortality in young suckling pigs varied significantly between the two affected sow farms. While mortality in suckling piglets reached almost 70 % in one sow herd, no increase in suckling piglet mortality was observed in the second sow farm. In all three cases, PEDV was confirmed in feces and small intestines by RT-qPCR. Phylogenetic analyses based on full-length PEDV genomes revealed high identity among strains from all three herds. Moreover, the German strains showed very high nucleotide identity (99.4 %) with a variant of PEDV (OH851) that was isolated in the United States in January 2014. This strain with insertions and deletions in the S-gene (so called INDEL strains) was reported to show lower virulence. Slightly lower identities were found with other strains from the US and Asia. CONCLUSION: Phylogenetic information on the distribution of PEDV strains in Europe is severely lacking. In this case report we demonstrate that acute outbreaks of PEDV occurred in southern Germany in 2014. Current strains were clearly different from isolates found in the 1980s and were closely related to a PEDV variant found in the US in 2014. Moreover, the present case report indicates that variant strains of PEDV, containing insertions and deletions in the S gene, which were reported to be of lower virulence, might be able to cause high mortality in suckling piglets.",2015 Jul 2,"['Stadler, Julia', 'Zoels, Susanne', 'Fux, Robert', 'Hanke, Dennis', 'Pohlmann, Anne', 'Blome, Sandra', 'Weissenböck, Herbert', 'Weissenbacher-Lang, Christiane', 'Ritzmann, Mathias', 'Ladinig, Andrea']",BMC Vet Res,,,True
9e17fa07642900d9491bf957db97cbe70bc39610,PMC,Monoclonal Antibody Combinations that Present Synergistic Neutralizing Activity: A Platform for Next-Generation Anti-Toxin Drugs,http://dx.doi.org/10.3390/toxins7061854,PMC4488679,26035486,CC BY,"Monoclonal antibodies (MAbs) are among the fastest-growing therapeutics and are being developed for a broad range of indications, including the neutralization of toxins, bacteria and viruses. Nevertheless, MAbs potency is still relatively low when compared to conventional polyclonal Ab preparations. Moreover, the efficacy of an individual neutralizing MAb may significantly be hampered by the potential absence or modification of its target epitope in a mutant or subtype of the infectious agent. These limitations of individual neutralizing MAbs can be overcome by using oligoclonal combinations of several MAbs with different specificities to the target antigen. Studies conducted in our lab and by others show that such combined MAb preparation may present substantial synergy in its potency over the calculated additive potency of its individual MAb components. Moreover, oligoclonal preparation is expected to be better suited to compensating for reduced efficacy due to epitope variation. In this review, the synergistic neutralization properties of combined oligoclonal Ab preparations are described. The effect of Ab affinity, autologous Fc fraction, and targeting a critical number of epitopes, as well as the unexpected contribution of non-neutralizing clones to the synergistic neutralizing effect are presented and discussed.",2015 May 29,"['Diamant, Eran', 'Torgeman, Amram', 'Ozeri, Eyal', 'Zichel, Ran']",Toxins (Basel),,,True
9450e90f9c678f1eb0ce33caac814ebc1b2e97e7,PMC,The Emerging Roles of Viroporins in ER Stress Response and Autophagy Induction during Virus Infection,http://dx.doi.org/10.3390/v7062749,PMC4488716,26053926,CC BY,"Viroporins are small hydrophobic viral proteins that oligomerize to form aqueous pores on cellular membranes. Studies in recent years have demonstrated that viroporins serve important functions during virus replication and contribute to viral pathogenicity. A number of viroporins have also been shown to localize to the endoplasmic reticulum (ER) and/or its associated membranous organelles. In fact, replication of most RNA viruses is closely linked to the ER, and has been found to cause ER stress in the infected cells. On the other hand, autophagy is an evolutionarily conserved “self-eating” mechanism that is also observed in cells infected with RNA viruses. Both ER stress and autophagy are also known to modulate a wide variety of signaling pathways including pro-inflammatory and innate immune response, thereby constituting a major aspect of host-virus interactions. In this review, the potential involvement of viroporins in virus-induced ER stress and autophagy will be discussed.",2015 Jun 4,"['Fung, To Sing', 'Torres, Jaume', 'Liu, Ding Xiang']",Viruses,,,True
a2b0f19c4b1270624987ede418ab8da1e8b55cdf,PMC,Protein-Protein Interactions of Viroporins in Coronaviruses and Paramyxoviruses: New Targets for Antivirals?,http://dx.doi.org/10.3390/v7062750,PMC4488717,26053927,CC BY,"Viroporins are members of a rapidly growing family of channel-forming small polypeptides found in viruses. The present review will be focused on recent structural and protein-protein interaction information involving two viroporins found in enveloped viruses that target the respiratory tract; (i) the envelope protein in coronaviruses and (ii) the small hydrophobic protein in paramyxoviruses. Deletion of these two viroporins leads to viral attenuation in vivo, whereas data from cell culture shows involvement in the regulation of stress and inflammation. The channel activity and structure of some representative members of these viroporins have been recently characterized in some detail. In addition, searches for protein-protein interactions using yeast-two hybrid techniques have shed light on possible functional roles for their exposed cytoplasmic domains. A deeper analysis of these interactions should not only provide a more complete overview of the multiple functions of these viroporins, but also suggest novel strategies that target protein-protein interactions as much needed antivirals. These should complement current efforts to block viroporin channel activity.",2015 Jun 4,"['Torres, Jaume', 'Surya, Wahyu', 'Li, Yan', 'Liu, Ding Xiang']",Viruses,,,True
b02612aa65049060e0a24064db96105458ac083b,PMC,IFITMs from Mycobacteria Confer Resistance to Influenza Virus When Expressed in Human Cells,http://dx.doi.org/10.3390/v7062759,PMC4488726,26075508,CC BY,"Interferon induced transmembrane proteins (IFITMs) found in vertebrates restrict infections by specific viruses. IFITM3 is known to be essential for restriction of influenza virus infections in both mice and humans. Vertebrate IFITMs are hypothesized to have derived from a horizontal gene transfer from bacteria to a primitive unicellular eukaryote. Since bacterial IFITMs share minimal amino acid identity with human IFITM3, we hypothesized that examination of bacterial IFITMs in human cells would provide insight into the essential characteristics necessary for antiviral activity of IFITMs. We examined IFITMs from Mycobacterium avium and Mycobacterium abscessus for potential antiviral activity. Both of these IFITMs conferred a moderate level of resistance to influenza virus in human cells, identifying them as functional homologues of IFITM3. Analysis of sequence elements shared by bacterial IFITMs and IFITM3 identified two hydrophobic domains, putative S-palmitoylation sites, and conserved phenylalanine residues associated with IFITM3 interactions, which are all necessary for IFITM3 antiviral activity. We observed that, like IFITM3, bacterial IFITMs were S-palmitoylated, albeit to a lesser degree. We also demonstrated the ability of a bacterial IFITM to co-immunoprecipitate with IFITM3 suggesting formation of a complex, and also visualized strong co-localization of bacterial IFITMs with IFITM3. However, the mycobacterial IFITMs lack the endocytic-targeting motif conserved in vertebrate IFITM3. As such, these bacterial proteins, when expressed alone, had diminished colocalization with cathepsin B-positive endolysosomal compartments that are the primary site of IFITM3-dependent influenza virus restriction. Though the precise evolutionary origin of vertebrate IFITMs is not known, our results support a model whereby transfer of a bacterial IFITM gene to eukaryotic cells may have provided a selective advantage against viral infection that was refined through the course of vertebrate evolution to include more robust signals for S-palmitoylation and localization to sites of endocytic virus trafficking.",2015 Jun 12,"['Melvin, William J.', 'McMichael, Temet M.', 'Chesarino, Nicholas M.', 'Hach, Jocelyn C.', 'Yount, Jacob S.']",Viruses,,,True
9aed1e2e3dc529e3863b89a60bb4e377e8c3a3e6,PMC,Viral Membrane Channels: Role and Function in the Virus Life Cycle,http://dx.doi.org/10.3390/v7062771,PMC4488738,26110585,CC BY,"Viroporins are small, hydrophobic trans-membrane viral proteins that oligomerize to form hydrophilic pores in the host cell membranes. These proteins are crucial for the pathogenicity and replication of viruses as they aid in various stages of the viral life cycle, from genome uncoating to viral release. In addition, the ion channel activity of viroporin causes disruption in the cellular ion homeostasis, in particular the calcium ion. Fluctuation in the calcium level triggers the activation of the host defensive programmed cell death pathways as well as the inflammasome, which in turn are being subverted for the viruses’ replication benefits. This review article summarizes recent developments in the functional investigation of viroporins from various viruses and their contributions to viral replication and virulence.",2015 Jun 23,"['Sze, Ching Wooen', 'Tan, Yee-Joo']",Viruses,,,True
471239798c6ed87995720ee1a73092b8b79b9549,PMC,Characterisation of Structural Proteins from Chronic Bee Paralysis Virus (CBPV) Using Mass Spectrometry,http://dx.doi.org/10.3390/v7062774,PMC4488741,26110588,CC BY,"Chronic bee paralysis virus (CBPV) is the etiological agent of chronic paralysis, an infectious and contagious disease in adult honeybees. CBPV is a positive single-stranded RNA virus which contains two major viral RNA fragments. RNA 1 (3674 nt) and RNA 2 (2305 nt) encode three and four putative open reading frames (ORFs), respectively. RNA 1 is thought to encode the viral RNA-dependent RNA polymerase (RdRp) since the amino acid sequence derived from ORF 3 shares similarities with the RdRP of families Nodaviridae and Tombusviridae. The genomic organization of CBPV and in silico analyses have suggested that RNA 1 encodes non-structural proteins, while RNA 2 encodes structural proteins, which are probably encoded by ORFs 2 and 3. In this study, purified CBPV particles were used to characterize virion proteins by mass spectrometry. Several polypeptides corresponding to proteins encoded by ORF 2 and 3 on RNA 2 were detected. Their role in the formation of the viral capsid is discussed.",2015 Jun 23,"['Chevin, Aurore', 'Coutard, Bruno', 'Blanchard, Philippe', 'Dabert-Gay, Anne-Sophie', 'Ribière-Chabert, Magali', 'Thiéry, Richard']",Viruses,,,True
c59c9a2c6315ed5aa7c437d1943fd94518119fd8,PMC,A Novel Chimeric Anti-PA Neutralizing Antibody for Postexposure Prophylaxis and Treatment of Anthrax,http://dx.doi.org/10.1038/srep11776,PMC4488766,26134518,CC BY,"Anthrax is a highly lethal infectious disease caused by the bacterium Bacillus anthracis, and the associated shock is closely related to the lethal toxin (LeTx) produced by the bacterium. The central role played by the 63 kDa protective antigen (PA63) region of LeTx in the pathophysiology of anthrax makes it an excellent therapeutic target. In the present study, a human/murine chimeric IgG mAb, hmPA6, was developed by inserting murine antibody variable regions into human constant regions using antibody engineering technology. hmPA6 expressed in 293F cells could neutralize LeTx both in vitro and in vivo. At a dose of 0.3 mg/kg, it could protect all tested rats from a lethal dose of LeTx. Even administration of 0.6 mg/kg hmPA6 48 h before LeTx challenge protected all tested rats. The results indicate that hmPA6 is a potential candidate for clinical application in anthrax treatment.",2015 Jul 2,"['Xiong, Siping', 'Tang, Qi', 'Liang, Xudong', 'Zhou, Tingting', 'Yang, Jin', 'Liu, Peng', 'Chen, Ya', 'Wang, Changjun', 'Feng, Zhenqing', 'Zhu, Jin']",Sci Rep,,,True
35f06fe8870be0c3cd7f0e9b47872a59c7590d7d,PMC,Modulation of the Immune Response to Respiratory Viruses by Vitamin D,http://dx.doi.org/10.3390/nu7064240,PMC4488782,26035247,CC BY,"Background: Vitamin D deficiency has been shown to be independently associated with increased risk of viral acute respiratory infection (ARI) in a number of observational studies, and meta-analysis of clinical trials of vitamin D supplementation for prevention of ARI has demonstrated protective effects. Several cellular studies have investigated the effects of vitamin D metabolites on immune responses to respiratory viruses, but syntheses of these reports are lacking. Scope: In this article, we review the literature reporting results of in vitro experiments investigating immunomodulatory actions of vitamin D metabolites in human respiratory epithelial cells infected with respiratory viruses. Key findings: Vitamin D metabolites do not consistently influence replication or clearance of rhinovirus, respiratory syncytial virus (RSV) or influenza A virus in human respiratory epithelial cell culture, although they do modulate expression and secretion of type 1 interferon, chemokines including CXCL8 and CXCL10 and pro-inflammatory cytokines, such as TNF and IL-6. Future research: More studies are needed to clarify the effects of vitamin D metabolites on respiratory virus-induced expression of cell surface markers mediating viral entry and bacterial adhesion to respiratory epithelial cells.",2015 May 29,"['Greiller, Claire L.', 'Martineau, Adrian R.']",Nutrients,,,True
5db737c9e3b8b52dd6c4778e9ade92d2ff9fadbe,PMC,Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice,http://dx.doi.org/10.1186/s13054-015-0983-9,PMC4490661,26067826,CC BY,"INTRODUCTION: Provision for the emergence of an influenza pandemic is an urgent issue. The discovery of a novel anti-influenza therapeutic approach would increase the effectiveness of traditional virus-based strategies. This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on influenza A virus (H1N1)-induced pneumonia in mice. METHODS: Nine-week-old male C57BL/6 mice were inoculated with H1N1, then anti-HMGB1 mAb or control mAb were administered intravenously at 1, 24 and 48 hours after H1N1 inoculation and the survival rate was analyzed. Lung lavage and histopathological analysis were performed on days 3, 5, 7 and 10 after inoculation. RESULTS: Anti-HMGB1 mAb significantly improved the survival rate of H1N1-inoculated mice (1 out of 15 versus 8 out of 15 deaths in the anti-HMGB1 mAb-treated group versus the control mAb-treated group, p < 0.01), although the treatment did not affect virus propagation in the lungs. The treatment also significantly attenuated histological changes and neutrophil infiltration in the lungs of H1N1-inoculated mice. This was associated with inhibition of HMGB1 and suppression of inflammatory cytokine/chemokine expression and oxidative stress enhancement, which were observed in H1N1-inoculated mice. The expression of receptor for advanced glycation end products and nuclear factor κB was attenuated by the treatment. CONCLUSIONS: Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0983-9) contains supplementary material, which is available to authorized users.",2015 Jun 11,"['Nosaka, Nobuyuki', 'Yashiro, Masato', 'Yamada, Mutsuko', 'Fujii, Yosuke', 'Tsukahara, Hirokazu', 'Liu, Keyue', 'Nishibori, Masahiro', 'Matsukawa, Akihiro', 'Morishima, Tsuneo']",Crit Care,,,True
bae2a5c3432eed55a087174498b80fe9f9725943,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.15.010715,PMC4490818,,CC BY,,2015 Jul 1,,Bull World Health Organ,,,False
5a717164844c095a4fb195350b44048059245b21,PMC,"Intranasal and oral vaccination with protein-based antigens: advantages, challenges and formulation strategies",http://dx.doi.org/10.1007/s13238-015-0164-2,PMC4491048,25944045,CC BY,"Most pathogens initiate their infections at the human mucosal surface. Therefore, mucosal vaccination, especially through oral or intranasal administration routes, is highly desired for infectious diseases. Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development. However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low immunogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions. This review aims to provide an up-to-date survey of the protein antigen-based vaccine formulation development, including the usage of immunostimulants and the optimization of vaccine delivery systems for intranasal and oral administrations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-015-0164-2) contains supplementary material, which is available to authorized users.",2015 Jul 6,"['Wang, Shujing', 'Liu, Huiqin', 'Zhang, Xinyi', 'Qian, Feng']",Protein Cell,,,False
ae44f456afccca76e1eec1637ce1af6041956c64,PMC,"Intranasal and oral vaccination with protein-based antigens: advantages, challenges and formulation strategies",http://dx.doi.org/10.1007/s13238-015-0164-2,PMC4491048,25944045,CC BY,"Most pathogens initiate their infections at the human mucosal surface. Therefore, mucosal vaccination, especially through oral or intranasal administration routes, is highly desired for infectious diseases. Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development. However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low immunogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions. This review aims to provide an up-to-date survey of the protein antigen-based vaccine formulation development, including the usage of immunostimulants and the optimization of vaccine delivery systems for intranasal and oral administrations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-015-0164-2) contains supplementary material, which is available to authorized users.",2015 Jul 6,"['Wang, Shujing', 'Liu, Huiqin', 'Zhang, Xinyi', 'Qian, Feng']",Protein Cell,,,True
2ba96cb3fe11b62cac4ae9816383256395239409,PMC,Factors associated with uptake of influenza vaccine in people aged 50 to 64 years in Hong Kong: a case–control study,http://dx.doi.org/10.1186/s12889-015-1990-0,PMC4491862,26148496,CC BY,"BACKGROUND: In Hong Kong, people aged 50–64 years were added as a recommended priority group (recommended group) for influenza vaccination by the Department of Health (DH) starting from 2011/12 onwards. The coverage rate of influenza vaccination for this age group was suboptimal at 8.5 % in 2012/13. This study investigates the factors associated with the uptake of influenza vaccination among adults in Hong Kong aged 50–64 years. METHODS: A case–control study was conducted in communities by street intercept interviews from 17 July to 15 August 2013. Cases were adults aged 50–64 years who had received the influenza vaccine in 2011/12 or 2012/13, while controls were the same as the cases, except they had not received the influenza vaccine in 2011/12 or 2012/13. Multiple logistic regression analysis was performed on the data to explore the associations between vaccination status and the variables. RESULTS: Six hundred and four respondents in total were interviewed and included in the analysis. There were 193 cases (vaccinated) and 411 controls (non-vaccinated), with a case-to-control ratio of 1:2.1. The following were strongly associated with vaccination compared to other factors: ‘eligible for free government vaccine’ (OR6.38, 95 % CI, 3.43-11.87, p < 0.001); ‘willing to receive flu vaccination for free’ (OR4.84, 95 % CI, 2.13-11.03, p < 0.001); ‘perceived having severe or moderate symptoms when contracting flu’ (OR2.90, 95 % CI, 1.21-6.97, p = 0.02), and ‘convenient to reach a vaccination location’ (OR2.87, 95 % CI, 1.06-7.74, p = 0.04). The majority of the cases (80.8 %) and controls (93.9 %) were not aware that they belonged to a recommended group for influenza vaccination and most (>80 %) were willing to be vaccinated if it was free. CONCLUSIONS: Factors related to free and convenient vaccination, the perception of the severity of symptoms when contracting influenza had a comparatively strong association with influenza vaccination uptake amongst 50–64 year olds, compared to other factors.",2015 Jul 7,"['Yeung, May PS', 'Ng, Stephen Kam-Cheung', 'Tong, Edmond Tak Fai', 'Chan, Stephen Sek-Kam', 'Coker, Richard']",BMC Public Health,,,True
6eb0faeda9396efaf96674c33b40395012a01e0a,PMC,Single-Stranded DNA Aptamers against Pathogens and Toxins: Identification and Biosensing Applications,http://dx.doi.org/10.1155/2015/419318,PMC4493287,26199940,CC BY,"Molecular recognition elements (MREs) can be short sequences of single-stranded DNA, RNA, small peptides, or antibody fragments. They can bind to user-defined targets with high affinity and specificity. There has been an increasing interest in the identification and application of nucleic acid molecular recognition elements, commonly known as aptamers, since they were first described in 1990 by the Gold and Szostak laboratories. A large number of target specific nucleic acids MREs and their applications are currently in the literature. This review first describes the general methodologies used in identifying single-stranded DNA (ssDNA) aptamers. It then summarizes advancements in the identification and biosensing application of ssDNA aptamers specific for bacteria, viruses, their associated molecules, and selected chemical toxins. Lastly, an overview of the basic principles of ssDNA aptamer-based biosensors is discussed.",2015 Jun 23,"['Hong, Ka Lok', 'Sooter, Letha J.']",Biomed Res Int,,,True
3ca43ade94501268228e5239d1717d4f6333d462,PMC,Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial,http://dx.doi.org/10.3390/vaccines1040398,PMC4494211,26344340,CC BY,"2013 marks a milestone year for plasmid DNA vaccine development as a first-in-class cytomegalovirus (CMV) DNA vaccine enters pivotal phase 3 testing. This vaccine consists of two plasmids expressing CMV antigens glycoprotein B (gB) and phosphoprotein 65 (pp65) formulated with a CRL1005 poloxamer and benzalkonium chloride (BAK) delivery system designed to enhance plasmid expression. The vaccine’s planned initial indication under investigation is for prevention of CMV reactivation in CMV-seropositive (CMV(+)) recipients of an allogeneic hematopoietic stem cell transplant (HCT). A randomized, double-blind placebo-controlled phase 2 proof-of-concept study provided initial evidence of the safety of this product in CMV(+) HCT recipients who underwent immune ablation conditioning regimens. This study revealed a significant reduction in viral load endpoints and increased frequencies of pp65-specific interferon-γ-producing T cells in vaccine recipients compared to placebo recipients. The results of this endpoint-defining trial provided the basis for defining the primary and secondary endpoints of a global phase 3 trial in HCT recipients. A case study is presented here describing the development history of this vaccine from product concept to initiation of the phase 3 trial.",2013 Sep 25,"['Smith, Larry R.', 'Wloch, Mary K.', 'Chaplin, Jennifer A.', 'Gerber, Michele', 'Rolland, Alain P.']",Vaccines (Basel),,,True
f78956e70c8bd1756ffb24ae47c35c3217bed384,PMC,Peptide Vaccine: Progress and Challenges,http://dx.doi.org/10.3390/vaccines2030515,PMC4494216,26344743,CC BY,"Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.",2014 Jul 2,"['Li, Weidang', 'Joshi, Medha D.', 'Singhania, Smita', 'Ramsey, Kyle H.', 'Murthy, Ashlesh K.']",Vaccines (Basel),,,True
653c1744be45d5e3ba3e9fb48edf6c6997976324,PMC,Vaccinia Virus LC16m8∆ as a Vaccine Vector for Clinical Applications,http://dx.doi.org/10.3390/vaccines2040755,PMC4494248,26344890,CC BY,"The LC16m8 strain of vaccinia virus, the active ingredient in the Japanese smallpox vaccine, was derived from the Lister/Elstree strain. LC16m8 is replication-competent and has been administered to over 100,000 infants and 3,000 adults with no serious adverse reactions. Despite this outstanding safety profile, the occurrence of spontaneously-generated large plaque-forming virulent LC16m8 revertants following passage in cell culture is a major drawback. We identified the gene responsible for the reversion and deleted the gene (B5R) from LC16m8 to derive LC16m8Δ. LC16m8∆ is non-pathogenic in immunodeficient severe combined immunodeficiency (SCID) mice, genetically-stable and does not reverse to a large-plaque phenotype upon passage in cell culture, even under conditions in which most LC16m8 populations are replaced by revertants. Moreover, LC16m8∆ is >500-fold more effective than the non-replicating vaccinia virus (VV), Modified Vaccinia Ankara (MVA), at inducing murine immune responses against pathogenic VV. LC16m8∆, which expresses the SIV gag gene, also induced anti-Gag CD8(+) T-cells more efficiently than MVA and another non-replicating VV, Dairen I minute-pock variants (DIs). Moreover, LC16m8∆ expressing HIV-1 Env in combination with a Sendai virus vector induced the production of anti-Env antibodies and CD8(+) T-cells. Thus, the safety and efficacy of LC16m8∆ mean that it represents an outstanding platform for the development of human vaccine vectors.",2014 Oct 17,"['Kidokoro, Minoru', 'Shida, Hisatoshi']",Vaccines (Basel),,,True
6be6ca48112c227ce80a36601ea8b464edbf1367,PMC,"Developing Universal Influenza Vaccines: Hitting the Nail, Not Just on the Head",http://dx.doi.org/10.3390/vaccines3020239,PMC4494343,26343187,CC BY,"Influenza viruses have a huge impact on public health. Current influenza vaccines need to be updated annually and protect poorly against antigenic drift variants or novel emerging subtypes. Vaccination against influenza can be improved in two important ways, either by inducing more broadly protective immune responses or by decreasing the time of vaccine production, which is relevant especially during a pandemic outbreak. In this review, we outline the current efforts to develop so-called “universal influenza vaccines”, describing antigens that may induce broadly protective immunity and novel vaccine production platforms that facilitate timely availability of vaccines.",2015 Mar 26,"['Wiersma, Lidewij C. M.', 'Rimmelzwaan, Guus F.', 'de Vries, Rory D.']",Vaccines (Basel),,,True
d51485f32ff85186571e9ec9de6d517f9180abe9,PMC,The Use of a Shelter Software (a) to Track Frequency and Selected Risk Factors for Feline Upper Respiratory Infection,http://dx.doi.org/10.3390/ani5020161,PMC4494401,26479227,CC BY,"SIMPLE SUMMARY: Feline upper respiratory infection is a common disease in animal shelters. Without monitoring, effective control and prevention is difficult. We looked at a software system (a) used in shelters across the United States to determine if it can be used to track URI frequency and risk factors in a population. Reports from the software system (a) were compared to data collected manually. This showed that data currently collected were not useful for tracking URI frequency and risk factors. However, potential exists to increase the practicality and usefulness of this shelter software system to monitor URI and other diseases. ABSTRACT: Objective—Feline upper respiratory infection (URI) is a common, multi-factorial infectious disease syndrome endemic to many animal shelters. Although a significant cause of morbidity and mortality in shelter cats, URI is seldom formally monitored in shelter cat populations. Without monitoring, effective control and prevention of this often endemic disease is difficult. We looked at an integrated case management software system (a) for animal care organizations, widely used in shelters across the United States. Shelter staff routinely enter information regarding individual animals and disease status, but do not commonly use the software system to track frequency of disease. The purpose of this study was to determine if the software system (a) can be used to track URI frequency and selected risk factors in a population, and to evaluate the quality and completeness of the data as currently collected in a shelter. Design (type of study)—Descriptive Survey. Animals (or Sample)—317 cats in an animal shelter. Procedures—Reports from the software system (a) containing data regarding daily inventory, daily intake, animal identification, location, age, vaccination status, URI diagnosis and URI duration were evaluated. The reports were compared to data collected manually by an observer (Ann Therese Kommedal) to assess discrepancies, completeness, timeliness, availability and accuracy. Data were collected 6 days a week over a 4 week period. Results—Comparisons between the software system (a) reports and manually collected reports showed that 93% of inventory reports were complete and of these 99% were accurate. Fifty-two percent of the vaccination reports were complete, of which 97% were accurate. The accuracy of the software system’s age reports was 76%. Two-hundred and twenty-three cats were assigned a positive or negative URI diagnosis by the observer. The predictive value of the URI status in the software system (a) was below 60% both for positive and negative URI diagnosis. Conclusions and Clinical Relevance—data currently collected and entered into the software systems in the study shelter, was not useful for tracking URI frequency and risk factors, due to issues with both data quality and capture. However, the potential exists to increase the practicality and usefulness of this shelter software system to monitor URI and other diseases. Relevant data points, i.e., health status at intake and outcome, vaccination date and status, as well as age, should be made mandatory to facilitate more useful data collection and reporting.",2015 Mar 25,"['Kommedal, Ann Therese', 'Wagner, Denae', 'Hurley, Kate']",Animals (Basel),,,True
a5d44eaf14b7ed5402af3501540147d36b314824,PMC,Large Eddy Simulation of Air Escape through a Hospital Isolation Room Single Hinged Doorway—Validation by Using Tracer Gases and Simulated Smoke Videos,http://dx.doi.org/10.1371/journal.pone.0130667,PMC4494857,26151865,CC BY,"The use of hospital isolation rooms has increased considerably in recent years due to the worldwide outbreaks of various emerging infectious diseases. However, the passage of staff through isolation room doors is suspected to be a cause of containment failure, especially in case of hinged doors. It is therefore important to minimize inadvertent contaminant airflow leakage across the doorway during such movements. To this end, it is essential to investigate the behavior of such airflows, especially the overall volume of air that can potentially leak across the doorway during door-opening and human passage. Experimental measurements using full-scale mock-ups are expensive and labour intensive. A useful alternative approach is the application of Computational Fluid Dynamics (CFD) modelling using a time-resolved Large Eddy Simulation (LES) method. In this study simulated air flow patterns are qualitatively compared with experimental ones, and the simulated total volume of air that escapes is compared with the experimentally measured volume. It is shown that the LES method is able to reproduce, at room scale, the complex transient airflows generated during door-opening/closing motions and the passage of a human figure through the doorway between two rooms. This was a basic test case that was performed in an isothermal environment without ventilation. However, the advantage of the CFD approach is that the addition of ventilation airflows and a temperature difference between the rooms is, in principle, a relatively simple task. A standard method to observe flow structures is dosing smoke into the flow. In this paper we introduce graphical methods to simulate smoke experiments by LES, making it very easy to compare the CFD simulation to the experiments. The results demonstrate that the transient CFD simulation is a promising tool to compare different isolation room scenarios without the need to construct full-scale experimental models. The CFD model is able to reproduce the complex airflows and estimate the volume of air escaping as a function of time. In this test, the calculated migrated air volume in the CFD model differed by 20% from the experimental tracer gas measurements. In the case containing only a hinged door operation, without passage, the difference was only 10%.",2015 Jul 7,"['Saarinen, Pekka E.', 'Kalliomäki, Petri', 'Tang, Julian W.', 'Koskela, Hannu']",PLoS One,,,True
c63e2bbb0915e7d4d40813d58286d51e80453507,PMC,Efficient generation of influenza virus with a mouse RNA polymerase I-driven all-in-one plasmid,http://dx.doi.org/10.1186/s12985-015-0321-5,PMC4495709,26093583,CC BY,"BACKGROUND: The current influenza vaccines are effective against seasonal influenza, but cannot be manufactured in a timely manner for a sudden pandemic or to be cost-effective to immunize huge flocks of birds. We propose a novel influenza vaccine composing a bacterial carrier and a plasmid cargo. In the immunized subjects, the bacterial carrier invades and releases its cargo into host cells where the plasmid expresses viral RNAs and proteins for reconstitution of attenuated influenza virus. Here we aimed to construct a mouse PolI-driven plasmid for efficient production of influenza virus. RESULTS: A plasmid was constructed to express all influenza viral RNAs and proteins. This all-in-one plasmid resulted in 10(5)–10(6) 50 % tissue culture infective dose (TCID(50))/mL of influenza A virus in baby hamster kidney (BHK-21) cells on the third day post-transfection, and also reconstituted influenza virus in Madin–Darby canine kidney (MDCK) and Chinese hamster ovary (CHO) cells. A 6-unit plasmid was constructed by deleting the HA and NA cassettes from the all-in-one plasmid. Cotransfection of BHK-21 cells with the 6-unit plasmid and the two other plasmids encoding the HA or NA genes resulted in influenza virus titers similar to those produced by the 1-plasmid method. CONCLUSIONS: An all-in-one plasmid and a 3-plasmid murine PolI-driven reverse genetics systems were developed, and efficiently reconstituted influenza virus in BHK-21 cells. The all-in-one plasmid may serve as a tool to determine the factors inhibiting virus generation from a large size plasmid. In addition, we recommend a simple and robust “1 + 2” approach to generate influenza vaccine seed virus.",2015 Jun 22,"['Zhang, Xiangmin', 'Curtiss, Roy']",Virol J,,,True
9f1936809149b1ca45c64b1468ba966bcdc4e331,PMC,"Outbreak of febrile illness caused by coxsackievirus A4 in a nursery school in Beijing, China",http://dx.doi.org/10.1186/s12985-015-0325-1,PMC4495935,26084565,CC BY,"BACKGROUND: Coxsackievirus A4 (CV-A4) is classified as human enterovirus A according to its serotype. CV-A4, an etiological agent of hand, foot, and mouth disease, affects children worldwide and can circulate in closed environments such as schools and hospitals for long periods. FINDINGS: An outbreak of febrile illness at a nursery school in Beijing, China, was confirmed to be caused by CV-A4. Phylogenetic analysis of the complete genome of the isolated strain showed that the virus belongs to the same cluster as the predominant CV-A4 strain in China. This outbreak was controlled by effective measures. CONCLUSIONS: The early identification of the pathogen and timely intervention may be the most critical factors in controlling an outbreak caused by CV-A4 in a preschool.",2015 Jun 18,"['Li, Jin-Song', 'Dong, Xiao-Gen', 'Qin, Meng', 'Xie, Zhi-Ping', 'Gao, Han-Chun', 'Yang, Jun-Yong', 'Yang, Xiao-Xin', 'Li, Dan-Di', 'Li, Jie', 'Duan, Zhao-Jun']",Virol J,,,True
21133fab598928cee990ee06d660b1d00f317175,PMC,Determining the Provincial and National Burden of Influenza-Associated Severe Acute Respiratory Illness in South Africa Using a Rapid Assessment Methodology,http://dx.doi.org/10.1371/journal.pone.0132078,PMC4496064,26154306,CC0,"Local disease burden data are necessary to set national influenza vaccination policy. In 2010 the population of South Africa was 50 million and the HIV prevalence was 11%. We used a previously developed methodology to determine severe influenza burden in South Africa. Hospitalized severe acute respiratory illness (SARI) incidence was calculated, stratified by HIV status, for four age groups using data from population-based surveillance in one site situated in Gauteng Province for 2009–2011. These rates were adjusted for each of the remaining 8 provinces based on their prevalence of risk factors for pneumonia and healthcare-seeking behavior. We estimated non-hospitalized influenza-associated SARI from healthcare utilization surveys at two sites and used the percent of SARI cases positive for influenza from sentinel surveillance to derive the influenza-associated SARI rate. We applied rates of hospitalized and non-hospitalized influenza-associated SARI to census data to calculate the national number of cases. The percent of SARI cases that tested positive for influenza ranged from 7–17% depending on age group, year, province and HIV status. In 2010, there were an estimated 21,555 total severe influenza cases in HIV-uninfected individuals and 13,876 in HIV-infected individuals. In 2011, there were an estimated 29,892 total severe influenza cases in HIV-uninfected individuals and 17,289 in HIV-infected individuals. The incidence of influenza-associated SARI was highest in children <5 years and was higher in HIV-infected than HIV-uninfected persons in all age groups. Influenza virus was associated with a substantial amount of severe disease, especially in young children and HIV-infected populations in South Africa.",2015 Jul 8,"['Murray, Jillian', 'Cohen, Adam', 'Walaza, Sibongile', 'Groome, Michelle', 'Madhi, Shabir', 'Variava, Ebrahim', 'Kahn, Kathleen', 'Dawood, Halima', 'Tempia, Stefano', 'Tshangela, Akhona', 'Venter, Marietje', 'Feikin, Daniel', 'Cohen, Cheryl']",PLoS One,,,True
db0761035838151a0b08a13888982ee36641b467,PMC,The Complex Role of STAT3 in Viral Infections,http://dx.doi.org/10.1155/2015/272359,PMC4496485,26199948,CC BY,"Signal transducer and activators of transcription-3 (STAT3) regulates diverse biological functions including cell growth, differentiation, and apoptosis. In addition, STAT3 plays a key role in regulating host immune and inflammatory responses and in the pathogenesis of many cancers. Several studies reported differential regulation of STAT3 in a range of viral infections. Interestingly, STAT3 appears to direct seemingly contradictory responses and both pro- and antiviral roles of STAT3 have been described. This review summarized the currently known functions of STAT3 in the regulation of viral replication and pathogenesis of viral infections. Some of the key unanswered questions and the gap in our current understanding of the role of STAT3 in viral pathogenesis are discussed.",2015 Jun 25,"Kuchipudi, Suresh V.",J Immunol Res,,,True
a0b13baa35ff28471952e5011f9411529d217f50,PMC,Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs,http://dx.doi.org/10.1186/s13567-015-0209-9,PMC4496848,26159607,CC BY,"Classical swine fever (CSF) causes major losses in pig farming, with various degrees of disease severity. Efficient live attenuated vaccines against classical swine fever virus (CSFV) are used routinely in endemic countries. However, despite intensive vaccination programs in these areas for more than 20 years, CSF has not been eradicated. Molecular epidemiology studies in these regions suggests that the virus circulating in the field has evolved under the positive selection pressure exerted by the immune response to the vaccine, leading to new attenuated viral variants. Recent work by our group demonstrated that a high proportion of persistently infected piglets can be generated by early postnatal infection with low and moderately virulent CSFV strains. Here, we studied the immune response to a hog cholera lapinised virus vaccine (HCLV), C-strain, in six-week-old persistently infected pigs following post-natal infection. CSFV-negative pigs were vaccinated as controls. The humoral and interferon gamma responses as well as the CSFV RNA loads were monitored for 21 days post-vaccination. No vaccine viral RNA was detected in the serum samples and tonsils from CSFV postnatally persistently infected pigs for 21 days post-vaccination. Furthermore, no E2-specific antibody response or neutralising antibody titres were shown in CSFV persistently infected vaccinated animals. Likewise, no of IFN-gamma producing cell response against CSFV or PHA was observed. To our knowledge, this is the first report demonstrating the absence of a response to vaccination in CSFV persistently infected pigs.",2015 Jul 9,"['Muñoz-González, Sara', 'Perez-Simó, Marta', 'Muñoz, Marta', 'Bohorquez, José Alejandro', 'Rosell, Rosa', 'Summerfield, Artur', 'Domingo, Mariano', 'Ruggli, Nicolas', 'Ganges, Llilianne']",Vet Res,,,True
e97dc3686befac553f8f1a09459ae59b089b4b8b,PMC,Proteomic analysis of purified turkey adenovirus 3 virions,http://dx.doi.org/10.1186/s13567-015-0214-z,PMC4497381,26159706,CC BY,"Turkey adenovirus 3 (TAdV-3) causes high mortality and significant economic losses to the turkey industry. However, little is known about the molecular determinants required for viral replication and pathogenesis. Moreover, TAdV-3 does not grow well in cell culture, thus detailed structural studies of the infectious particle is particularly challenging. To develop a better understanding of virus-host interactions, we performed a comprehensive proteomic analysis of proteinase K treated purified TAdV-3 virions isolated from spleens of infected turkeys, by utilizing one-dimensional liquid chromatography mass spectrometry. Our analysis resulted in the identification of 13 viral proteins associated with TAdV-3 virions including a novel uncharacterized TaV3gp04 protein. Further, we detected 18 host proteins in purified virions, many of which are involved in cell-to cell spread, cytoskeleton dynamics and virus replication. Notably, seven of these host proteins have not yet been reported to be present in any other purified virus. In addition, five of these proteins are known antiviral host restriction factors. The availability of reagents allowed us to identify two cellular proteins (collagen alpha-1 (VI) chain and haemoglobin) in the purified TAdV-3 preparations. These results represent the first comprehensive proteomic profile of TAdV-3 and may provide information for illustrating TAdV-3 replication and pathogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-015-0214-z) contains supplementary material, which is available to authorized users.",2015 Jul 9,"['Kumar, Pankaj', 'van den Hurk, Jan', 'Ayalew, Lisanework E.', 'Gaba, Amit', 'Tikoo, Suresh K.']",Vet Res,,,True
76241f85fbee07bdf466214c02c4bccd79706436,PMC,Novel circular single-stranded DNA viruses identified in marine invertebrates reveal high sequence diversity and consistent predicted intrinsic disorder patterns within putative structural proteins,http://dx.doi.org/10.3389/fmicb.2015.00696,PMC4498126,26217327,CC BY,"Viral metagenomics has recently revealed the ubiquitous and diverse nature of single-stranded DNA (ssDNA) viruses that encode a conserved replication initiator protein (Rep) in the marine environment. Although eukaryotic circular Rep-encoding ssDNA (CRESS-DNA) viruses were originally thought to only infect plants and vertebrates, recent studies have identified these viruses in a number of invertebrates. To further explore CRESS-DNA viruses in the marine environment, this study surveyed CRESS-DNA viruses in various marine invertebrate species. A total of 27 novel CRESS-DNA genomes, with Reps that share less than 60.1% identity with previously reported viruses, were recovered from 21 invertebrate species, mainly crustaceans. Phylogenetic analysis based on the Rep revealed a novel clade of CRESS-DNA viruses that included approximately one third of the marine invertebrate associated viruses identified here and whose members may represent a novel family. Investigation of putative capsid proteins (Cap) encoded within the eukaryotic CRESS-DNA viral genomes from this study and those in GenBank demonstrated conserved patterns of predicted intrinsically disordered regions (IDRs), which can be used to complement similarity-based searches to identify divergent structural proteins within novel genomes. Overall, this study expands our knowledge of CRESS-DNA viruses associated with invertebrates and explores a new tool to evaluate divergent structural proteins encoded by these viruses.",2015 Jul 10,"['Rosario, Karyna', 'Schenck, Ryan O.', 'Harbeitner, Rachel C.', 'Lawler, Stephanie N.', 'Breitbart, Mya']",Front Microbiol,,,True
6044c9d0aae3d02db03c409496ca81f8f83ebeab,PMC,Meta-genomic analysis of toilet waste from long distance flights; a step towards global surveillance of infectious diseases and antimicrobial resistance,http://dx.doi.org/10.1038/srep11444,PMC4498435,26161690,CC BY,"Human populations worldwide are increasingly confronted with infectious diseases and antimicrobial resistance spreading faster and appearing more frequently. Knowledge regarding their occurrence and worldwide transmission is important to control outbreaks and prevent epidemics. Here, we performed shotgun sequencing of toilet waste from 18 international airplanes arriving in Copenhagen, Denmark, from nine cities in three world regions. An average of 18.6 Gb (14.8 to 25.7 Gb) of raw Illumina paired end sequence data was generated, cleaned, trimmed and mapped against reference sequence databases for bacteria and antimicrobial resistance genes. An average of 106,839 (0.06%) reads were assigned to resistance genes with genes encoding resistance to tetracycline, macrolide and beta-lactam resistance genes as the most abundant in all samples. We found significantly higher abundance and diversity of genes encoding antimicrobial resistance, including critical important resistance (e.g. bla(CTX-M)) carried on airplanes from South Asia compared to North America. Presence of Salmonella enterica and norovirus were also detected in higher amounts from South Asia, whereas Clostridium difficile was most abundant in samples from North America. Our study provides a first step towards a potential novel strategy for global surveillance enabling simultaneous detection of multiple human health threatening genetic elements, infectious agents and resistance genes.",2015 Jul 10,"['Nordahl Petersen, Thomas', 'Rasmussen, Simon', 'Hasman, Henrik', 'Carøe, Christian', 'Bælum, Jacob', 'Charlotte Schultz, Anna', 'Bergmark, Lasse', 'Svendsen, Christina A.', 'Lund, Ole', 'Sicheritz-Pontén, Thomas', 'Aarestrup, Frank M.']",Sci Rep,,,True
f4ac2b1e9b9523671d7c38c27a19f1eec2e15d75,PMC,Meta-genomic analysis of toilet waste from long distance flights; a step towards global surveillance of infectious diseases and antimicrobial resistance,http://dx.doi.org/10.1038/srep11444,PMC4498435,26161690,CC BY,"Human populations worldwide are increasingly confronted with infectious diseases and antimicrobial resistance spreading faster and appearing more frequently. Knowledge regarding their occurrence and worldwide transmission is important to control outbreaks and prevent epidemics. Here, we performed shotgun sequencing of toilet waste from 18 international airplanes arriving in Copenhagen, Denmark, from nine cities in three world regions. An average of 18.6 Gb (14.8 to 25.7 Gb) of raw Illumina paired end sequence data was generated, cleaned, trimmed and mapped against reference sequence databases for bacteria and antimicrobial resistance genes. An average of 106,839 (0.06%) reads were assigned to resistance genes with genes encoding resistance to tetracycline, macrolide and beta-lactam resistance genes as the most abundant in all samples. We found significantly higher abundance and diversity of genes encoding antimicrobial resistance, including critical important resistance (e.g. bla(CTX-M)) carried on airplanes from South Asia compared to North America. Presence of Salmonella enterica and norovirus were also detected in higher amounts from South Asia, whereas Clostridium difficile was most abundant in samples from North America. Our study provides a first step towards a potential novel strategy for global surveillance enabling simultaneous detection of multiple human health threatening genetic elements, infectious agents and resistance genes.",2015 Jul 10,"['Nordahl Petersen, Thomas', 'Rasmussen, Simon', 'Hasman, Henrik', 'Carøe, Christian', 'Bælum, Jacob', 'Charlotte Schultz, Anna', 'Bergmark, Lasse', 'Svendsen, Christina A.', 'Lund, Ole', 'Sicheritz-Pontén, Thomas', 'Aarestrup, Frank M.']",Sci Rep,,,True
a1d863f8297bd6185abeb6564af22eac8bdd3fd3,PMC,Development of Recombinase Polymerase Amplification Assays for Detection of Orientia tsutsugamushi or Rickettsia typhi,http://dx.doi.org/10.1371/journal.pntd.0003884,PMC4498641,26161793,CC0,"Sensitive, specific and rapid diagnostic tests for the detection of Orientia tsutsugamushi (O. tsutsugamushi) and Rickettsia typhi (R. typhi), the causative agents of scrub typhus and murine typhus, respectively, are necessary to accurately and promptly diagnose patients and ensure that they receive proper treatment. Recombinase polymerase amplification (RPA) assays using a lateral flow test (RPA-nfo) and real-time fluorescent detection (RPA-exo) were developed targeting the 47-kDa gene of O. tsutsugamushi or 17 kDa gene of R. typhi. The RPA assay was capable of detecting O. tsutsugamushi or R. typhi at levels comparable to that of the quantitative PCR method. Both the RPA-nfo and RPA-exo methods performed similarly with regards to sensitivity when detecting the 17 kDa gene of R. typhi. On the contrary, RPA-exo performed better than RPA-nfo in detecting the 47 kDa gene of O. tsutsugamushi. The clinical performance of the O. tsutsugamushi RPA assay was evaluated using either human patient samples or infected mouse samples. Eight out of ten PCR confirmed positives were determined positive by RPA, and all PCR confirmed negative samples were negative by RPA. Similar results were obtained for R. typhi spiked patient sera. The assays were able to differentiate O. tsutsugamushi and R. typhi from other phylogenetically related bacteria as well as mouse and human DNA. Furthermore, the RPA-nfo reaction was completed in 20 minutes at 37(o)C followed by a 10 minute incubation at room temperature for development of an immunochromatographic strip. The RPA-exo reaction was completed in 20 minutes at 39(o)C. The implementation of a cross contamination proof cassette to detect the RPA-nfo fluorescent amplicons provided an alternative to regular lateral flow detection strips, which are more prone to cross contamination. The RPA assays provide a highly time-efficient, sensitive and specific alternative to other methods for diagnosing scrub typhus or murine typhus.",2015 Jul 10,"['Chao, Chien-Chung', 'Belinskaya, Tatyana', 'Zhang, Zhiwen', 'Ching, Wei-Mei']",PLoS Negl Trop Dis,,,True
ae0144eb4ec61e7765eed001bc8a9c775cd31b67,PMC,"Public Health Responses to Reemergence of Animal Rabies, Taiwan, July 16–December 28, 2013",http://dx.doi.org/10.1371/journal.pone.0132160,PMC4498755,26162074,CC BY,"Taiwan had been free of indigenous human and animal rabies case since canine rabies was eliminated in 1961. In July 2013, rabies was confirmed among three wild ferret-badgers, prompting public health response to prevent human rabies cases. This descriptive study reports the immediate response to the reemergence of rabies in Taiwan. Response included enhanced surveillance for human rabies cases by testing stored cerebrospinal fluids (CSF) from patients with encephalitides of unknown cause by RT-PCR, prioritizing vaccine use for postexposure prophylaxis (PEP) during periods of vaccine shortage and subsequent expansion of PEP, surveillance of animal bites using information obtained from vaccine application, roll out of preexposure prophylaxis (PrEP) with vaccine stock restoration, surveillance for adverse events following immunization (AEFI), and ensuring surge capacity to respond to general public inquiries by phone and training for healthcare professionals. Enhanced surveillance for human rabies found no cases after testing 205 stored CSF specimens collected during January 2010–July 2013. During July 16 to December 28, 2013, we received 8,241 rabies PEP application; 6,634 (80.5%) were consistent with recommendations. Among the 6,501persons who received at least one dose of rabies vaccine postexposure, 4,953 (76.2%) persons who were bitten by dogs; only 59 (0.9%) persons were bitten by ferret-badgers. During the study period, 6,247 persons received preexposure prophylaxis. There were 23 reports of AEFI; but no anaphylaxis, Guillain-Barré syndrome, or acute disseminated encephalomyelitis were found. During the study period, there were 40,312 calls to the Taiwan Centers for Disease Control hotline, of which, 8,692 (22%) were related to rabies. Recent identification of rabies among ferret-badgers in a previously rabies-free country prompted rapid response. To date, no human rabies has been identified. Continued multifaceted surveillance and interministerial collaboration are crucial to achieve the goal of rabies-free status in Taiwan.",2015 Jul 10,"['Huang, Angela Song-En', 'Chen, Wan-Chin', 'Huang, Wan-Ting', 'Huang, Shih-Tse', 'Lo, Yi-Chun', 'Wei, Sung-Hsi', 'Kuo, Hung-Wei', 'Chan, Pei-Chun', 'Hung, Min-Nan', 'Liu, Yu-Lun', 'Mu, Jung-Jung', 'Yang, Jyh-Yuan', 'Liu, Ding-Ping', 'Chou, Jih-Haw', 'Chuang, Jen-Hsiang', 'Chang, Feng-Yee']",PLoS One,,,True
d135acb9011d47a0f0d9e2b6542cb86539042fdf,PMC,Evaluation of farm-level parameters derived from animal movements for use in risk-based surveillance programmes of cattle in Switzerland,http://dx.doi.org/10.1186/s12917-015-0468-8,PMC4499910,26170195,CC BY,"BACKGROUND: This study focused on the descriptive analysis of cattle movements and farm-level parameters derived from cattle movements, which are considered to be generically suitable for risk-based surveillance systems in Switzerland for diseases where animal movements constitute an important risk pathway. METHODS: A framework was developed to select farms for surveillance based on a risk score summarizing 5 parameters. The proposed framework was validated using data from the bovine viral diarrhoea (BVD) surveillance programme in 2013. RESULTS: A cumulative score was calculated per farm, including the following parameters; the maximum monthly ingoing contact chain (in 2012), the average number of animals per incoming movement, use of mixed alpine pastures and the number of weeks in 2012 a farm had movements registered. The final score for the farm depended on the distribution of the parameters. Different cut offs; 50, 90, 95 and 99 %, were explored. The final scores ranged between 0 and 5. Validation of the scores against results from the BVD surveillance programme 2013 gave promising results for setting the cut off for each of the five selected farm level criteria at the 50th percentile. Restricting testing to farms with a score ≥ 2 would have resulted in the same number of detected BVD positive farms as testing all farms, i.e., the outcome of the 2013 surveillance programme could have been reached with a smaller survey. CONCLUSIONS: The seasonality and time dependency of the activity of single farms in the networks requires a careful assessment of the actual time period included to determine farm level criteria. However, selecting farms in the sample for risk-based surveillance can be optimized with the proposed scoring system. The system was validated using data from the BVD eradication program. The proposed method is a promising framework for the selection of farms according to the risk of infection based on animal movements.",2015 Jul 14,"['Schärrer, Sara', 'Widgren, Stefan', 'Schwermer, Heinzpeter', 'Lindberg, Ann', 'Vidondo, Beatriz', 'Zinsstag, Jakob', 'Reist, Martin']",BMC Vet Res,,,True
733c577e6a1dea9aab436bce4d918f08dfd27371,PMC,Ultraviolet Light (UV) Inactivation of Porcine Parvovirus in Liquid Plasma and Effect of UV Irradiated Spray Dried Porcine Plasma on Performance of Weaned Pigs,http://dx.doi.org/10.1371/journal.pone.0133008,PMC4501813,26171968,CC BY,"A novel ultraviolet light irradiation (UV-C, 254 nm) process was designed as an additional safety feature for manufacturing of spray dried porcine plasma (SDPP). In Exp. 1, three 10-L batches of bovine plasma were inoculated with 10(5.2±0.12) tissue culture infectious dose 50 (TCID(50)) of porcine parvovirus (PPV) per mL of plasma and subjected to UV-C ranging from 0 to 9180 J/L. No viable PPV was detected in bovine plasma by micro-titer assay in SK6 cell culture after UV-C at 2295 J/L. In Exp. 2, porcine plasma was subjected to UV-C (3672 J/L), then spray dried and mixed in complete mash diets. Diets were a control without SDPP (Control), UV-C SDPP either at 3% (UVSDPP3) or 6% (UVSDPP6) and non-UV-C SDPP at 3% (SDPP3) or 6% (SDPP6). Diets were fed ad libitum to 320 weaned pigs (26 d of age; 16 pens/diet; 4 pigs/pen) for 14 d after weaning and a common diet was fed d 15 to 28. During d 0 to 14, pigs fed UVSDPP3, UVSDPP6, or SDPP6 had higher (P < 0.05) weight gain and feed intake than control. During d 0 to 28, pigs fed UVSDPP3 and UVSDPP6 had higher (P < 0.05) weight gain and feed intake than control and SDPP3, and SDPP6 had higher (P < 0.05) feed intake than control. Also, pigs fed UVSDPP had higher (P < 0.05) weight gain than pigs fed SDPP. In conclusion, UV-C inactivated PPV in liquid plasma and UVSDPP used in pig feed had no detrimental effects on pig performance.",2015 Jul 14,"['Polo, Javier', 'Rodríguez, Carmen', 'Ródenas, Jesús', 'Russell, Louis E.', 'Campbell, Joy M.', 'Crenshaw, Joe D.', 'Torrallardona, David', 'Pujols, Joan']",PLoS One,,,True
0d8ae2d2ad6343782f8f7c078d00c14206f16230,PMC,Research Driven by Curiosity: The Journey from Basic Molecular Biology and Virology to Studies of Human Pathogenic Coronaviruses,http://dx.doi.org/10.1371/journal.ppat.1005023,PMC4501819,26172373,CC BY,,2015 Jul 14,"Perlman, Stanley",PLoS Pathog,,,False
c1722fc1da22b2ccf5565ccf81a1677c2994aeee,PMC,EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT,http://dx.doi.org/10.1038/srep11494,PMC4503950,26177797,CC BY,"Lung carcinogenesis is a complex process that occurs in unregulated inflammatory environment. EGCG has been extensively investigated as a multi-targeting anti-tumor and anti-inflammatory compound. In this study, we demonstrated a novel mechanism by which EGCG reverses the neutrophil elastase-induced migration of A549 cells. We found that neutrophil elastase directly triggered human adenocarcinoma A549 cell migration and that EGCG suppressed the elevation of tumor cell migration induced by neutrophil elastase. We observed that EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity based on the CDOCKER algorithm, MD stimulation by GROMACS, SPR assay and elastase enzymatic activity assay. As the natural inhibitor of neutrophil elastase, α1-antitrypsin is synthesized in tumor cells. We further demonstrated that the expression of α1-antitrypsin was up-regulated after EGCG treatment in neutrophil elastase-treated A549 cells. We preliminarily discovered that the EGCG-mediated induction of α1-antitrypsin expression might be correlated with the regulatory effect of EGCG on the PI3K/Akt pathway. Overall, our results suggest that EGCG ameliorates the neutrophil elastase-induced migration of A549 cells. The mechanism underlying this effect may include two processes: EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity; EGCG enhances the expression of α1-antitrypsin by regulating the PI3K/AKT pathway.",2015 Jul 16,"['Xiaokaiti, Yilixiati', 'Wu, Haoming', 'Chen, Ya', 'Yang, Haopeng', 'Duan, Jianhui', 'Li, Xin', 'Pan, Yan', 'Tie, Lu', 'Zhang, Liangren', 'Li, Xuejun']",Sci Rep,,,True
fb6b4f00d820aad697369de4f7f29b709541e973,PMC,Identification and pathogenicity of a variant porcine epidemic diarrhea virus field strain with reduced virulence,http://dx.doi.org/10.1186/s12985-015-0314-4,PMC4504071,26063495,CC BY,"BACKGROUND: Since 2010, a variant Porcine epidemic diarrhea virus (PEDV), which causes an acute, highly contagious, and devastating viral enteric disease with a high mortality rate in suckling pigs, broke out in China and spread rapidly to neighboring countries, even to the North America. This virus gradually became the main subtype of PEDV worldwide. However, there were no reports of mild pathogenicity of a variant porcine epidemic diarrhea virus in China. FINDINGS: In 2013, a PEDV-positive sample from a sow with very mild clinical sign was used to inoculate in Vero cells to isolate the virus. This PEDV field strain, designated FL2013 strain, was successfully propagated and genetically characterized. The phylogenetic trees based upon either the complete genome or S gene showed that the FL2013 strain belongs to the genogroup G2b. The S gene of FL2013 has a 7-aa deletion (FEKVHVQ) in the C-terminus comparison with the other G2 PEDV sequences. Further comparative pathology study indicated that the FL2013 strain had reduced virulence to newborn piglets. CONCLUSIONS: A novel variant PEDV strain FL2013 with reduced virulence, as determined by the pathological study, was identified from east China. This strain is closely related to the genogroup- 2 PEDV strains prevalent in the U.S. and China currently, but had a short deletion at the 3′- end of the spike gene.",2015 Jun 12,"['Zhang, Xiangbin', 'Pan, Yongfei', 'Wang, Dongdong', 'Tian, Xiaoyan', 'Song, Yanhua', 'Cao, Yongchang']",Virol J,,,True
333a04fb2ab37297b4591e7d6179fd731f5c1bf3,PMC,Clinical and molecular investigation of a canine distemper outbreak and vector-borne infections in a group of rescue dogs imported from Hungary to Switzerland,http://dx.doi.org/10.1186/s12917-015-0471-0,PMC4504088,26179635,CC BY,"BACKGROUND: Canine distemper virus (CDV) is a major pathogen of dogs and wild carnivores worldwide. In Switzerland, distemper in domestic dogs is rarely reported. In recent years, the import of dogs from Eastern Europe to Switzerland has steadily increased. In the present study, we describe a distemper outbreak in 15 rescue dogs that were imported from Hungary to Switzerland by an animal welfare organisation. The data on vaccination and medical history were recorded (14 dogs), and the samples were collected to investigate CDV and vector-borne infections (13 dogs) and canine parvovirus infection (12 dogs). The dogs were monitored for six months. RESULTS: One dog was euthanised directly after import. Thirteen dogs showed clinical signs after arrival, i.e., diarrhoea (57 %), coughing (43 %) and nasal and/or ocular discharge (21 %); radiographic findings that were compatible with bronchopneumonia were present in four dogs. CDV infection was diagnosed in 11 dogs (85 %); 10 dogs (91 %) tested PCR-positive in conjunctival swabs. Vector-borne infections (Babesia spp., Leishmania infantum, Dirofilaria immitis) were found in 4 dogs (31 %). Three dogs were hospitalized, and six dogs received ambulatory therapy for up to two months until recovery. None of the dogs developed neurological disease. CDV shedding was detected for a period of up to four months. Because dogs were put under strict quarantine until CDV shedding ceased, CDV did not spread to any other dogs. The CDV isolates showed 99 % sequence identity in the HA gene among each other and belonged to the Arctic-like lineage of CDV. CONCLUSIONS: The present study highlights the imminent risks of spreading contagious viral and vector-borne infections through the non-selective import of sick dogs and dogs with incomplete vaccination from Eastern Europe. CDV shedding was detected for several months after the cessation of clinical signs, which emphasised the roles of asymptomatic carriers in CDV epidemiology. A long-term follow-up using sensitive PCR and strict quarantine measures is of upmost importance in preventing the spread of infection. Dog owners and animal welfare organisations should be educated regarding the importance of complete vaccinations and the impact of dog imports on the spread of viral and vector-borne pathogens.",2015 Jul 16,"['Willi, Barbara', 'Spiri, Andrea M.', 'Meli, Marina L.', 'Grimm, Felix', 'Beatrice, Laura', 'Riond, Barbara', 'Bley, Tim', 'Jordi, Rolf', 'Dennler, Matthias', 'Hofmann-Lehmann, Regina']",BMC Vet Res,,,True
162c064dae8c02e477c00bbcd60b974ae794649f,PMC,Potential Biases in Estimating Absolute and Relative Case-Fatality Risks during Outbreaks,http://dx.doi.org/10.1371/journal.pntd.0003846,PMC4504518,26181387,CC BY,"Estimating the case-fatality risk (CFR)—the probability that a person dies from an infection given that they are a case—is a high priority in epidemiologic investigation of newly emerging infectious diseases and sometimes in new outbreaks of known infectious diseases. The data available to estimate the overall CFR are often gathered for other purposes (e.g., surveillance) in challenging circumstances. We describe two forms of bias that may affect the estimation of the overall CFR—preferential ascertainment of severe cases and bias from reporting delays—and review solutions that have been proposed and implemented in past epidemics. Also of interest is the estimation of the causal impact of specific interventions (e.g., hospitalization, or hospitalization at a particular hospital) on survival, which can be estimated as a relative CFR for two or more groups. When observational data are used for this purpose, three more sources of bias may arise: confounding, survivorship bias, and selection due to preferential inclusion in surveillance datasets of those who are hospitalized and/or die. We illustrate these biases and caution against causal interpretation of differential CFR among those receiving different interventions in observational datasets. Again, we discuss ways to reduce these biases, particularly by estimating outcomes in smaller but more systematically defined cohorts ascertained before the onset of symptoms, such as those identified by forward contact tracing. Finally, we discuss the circumstances in which these biases may affect non-causal interpretation of risk factors for death among cases.",2015 Jul 16,"['Lipsitch, Marc', 'Donnelly, Christl A.', 'Fraser, Christophe', 'Blake, Isobel M.', 'Cori, Anne', 'Dorigatti, Ilaria', 'Ferguson, Neil M.', 'Garske, Tini', 'Mills, Harriet L.', 'Riley, Steven', 'Van Kerkhove, Maria D.', 'Hernán, Miguel A.']",PLoS Negl Trop Dis,,,True
69f5726e6b53f93b94630c1388479879f49f456e,PMC,"Objectives, design and enrollment results from the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure Study (INSPIRE)",http://dx.doi.org/10.1186/s12890-015-0040-0,PMC4506623,26021723,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) during infancy has been consistently associated with an increased risk of childhood asthma. In addition, evidence supports that this relationship is causal. However, the mechanisms through which RSV contributes to asthma development are not understood. The INSPIRE (Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure) study objectives are to: 1) characterize the host phenotypic response to RSV infection in infancy and the risk of recurrent wheeze and asthma, 2) identify the immune response and lung injury patterns of RSV infection that are associated with the development of early childhood wheezing illness and asthma, and 3) determine the contribution of specific RSV strains to early childhood wheezing and asthma development. This article describes the INSPIRE study, including study aims, design, recruitment results, and enrolled population characteristics. METHODS/DESIGN: The cohort is a population based longitudinal birth cohort of term healthy infants enrolled during the first months of life over a two year period. Respiratory infection surveillance was conducted from November to March of the first year of life, through surveys administered every two weeks. In-person illness visits were conducted if infants met pre-specified criteria for a respiratory illness visit. Infants will be followed annually to ages 3-4 years for assessment of the primary endpoint: wheezing illness. Nasal, urine, stool and blood samples were collected at various time points throughout the study for measurements of host and viral factors that predict wheezing illness. Nested case-control studies will additionally be used to address other primary and secondary hypotheses. DISCUSSION: In the INSPIRE study, 1952 infants (48% female) were enrolled during the two enrollment years and follow-up will continue through 2016. The mean age of enrollment was 60 days. During winter viral season, more than 14,000 surveillance surveys were carried out resulting in 2,103 respiratory illness visits on 1189 infants. First year follow-up has been completed on over 95% percent of participants from the first year of enrollment. With ongoing follow-up for wheezing and childhood asthma outcomes, the INSPIRE study will advance our understanding of the complex causal relationship between RSV infection and early childhood wheezing and asthma.",2015 Apr 30,"['Larkin, Emma K', 'Gebretsadik, Tebeb', 'Moore, Martin L', 'Anderson, Larry J', 'Dupont, William D', 'Chappell, James D', 'Minton, Patricia A', 'Peebles, R Stokes', 'Moore, Paul E', 'Valet, Robert S', 'Arnold, Donald H', 'Rosas-Salazar, Christian', 'Das, Suman R', 'Polack, Fernando P', 'Hartert, Tina V', None]",BMC Pulm Med,,,True
7a9b57f8fdbedfe909d69cf53de24646684624f3,PMC,Functions of the 5′ and 3′ ends of calicivirus genomes,http://dx.doi.org/10.1016/j.virusres.2015.02.002,PMC4509552,25678268,CC BY,"The Caliciviridae family of small positive sense RNA viruses contains a diverse range of pathogens of both man and animals. The molecular mechanisms of calicivirus genome replication and translation have not been as widely studied as many other RNA viruses. With the relatively recent development of robust cell culture and reverse genetics systems for several members of the Caliciviridae family, a more in-depth analysis of the finer detail of the viral life cycle has now been obtained. As a result, the identification and characterization of the role of RNA structures in the calicivirus life cycle has also been possible. This review aims to summarize the current state of knowledge with respect to the role of RNA structures at the termini of calicivirus genomes.",2015 Aug 3,"['Alhatlani, Bader', 'Vashist, Surender', 'Goodfellow, Ian']",Virus Res,,,False
25a160364a2e056a097e4520f64c49c63140da6c,PMC,The Interferon-Inducible Mouse Apolipoprotein L9 and Prohibitins Cooperate to Restrict Theiler’s Virus Replication,http://dx.doi.org/10.1371/journal.pone.0133190,PMC4510265,26196674,CC BY,"Apolipoprotein L9b (Apol9b) is an interferon-stimulated gene (ISG) that has antiviral activity and is weakly expressed in primary mouse neurons as compared to other cell types. Here, we show that both Apol9 isoforms (Apol9b and Apol9a) inhibit replication of Theiler’s murine encephalomyelitis virus (TMEV) but not replication of vesicular stomatitis virus (VSV), Murid herpesvirus-4 (MuHV-4), or infection by a lentiviral vector. Apol9 genes are strongly expressed in mouse liver and, to a lesser extent, in pancreas, adipose tissue and intestine. Their expression is increased by type I interferon and viral infection. In contrast to genuine apolipoproteins that are involved in lipid transport, ApoL9 has an intracytoplasmic localization and does not seem to be secreted. The cytoplasmic localization of ApoL9 is in line with the observation that ApoL9 inhibits the replication step of TMEV infection. In contrast to human ApoL6, ApoL9 did not sensitize cells to apoptosis, in spite of the presence of a conserved putative BH3 domain, required for antiviral activity. ApoL9a and b isoforms interact with cellular prohibitin 1 (Phb1) and prohibitin 2 (Phb2) and this interaction might contribute to ApoL9 antiviral activity. Knocking down Phb2 slightly increased TMEV replication, irrespective of ApoL9 overexpression. The antiviral activity of prohibitins against TMEV contrasts with the pro-viral activity of prohibitins observed for VSV and reported previously for Dengue 2 (DENV-2), Chikungunya (CHIKV) and influenza H5N1 viruses. ApoL9 is thus an example of ISG displaying a narrow antiviral range, which likely acts in complex with prohibitins to restrict TMEV replication.",2015 Jul 21,"['Kreit, Marguerite', 'Vertommen, Didier', 'Gillet, Laurent', 'Michiels, Thomas']",PLoS One,,,True
95b1f681cfe2bb33c6433b07cd38f0ed3ce3667d,PMC,9-O-Acetylation of sialic acids is catalysed by CASD1 via a covalent acetyl-enzyme intermediate,http://dx.doi.org/10.1038/ncomms8673,PMC4510713,26169044,CC BY,"Sialic acids, terminal sugars of glycoproteins and glycolipids, play important roles in development, cellular recognition processes and host–pathogen interactions. A common modification of sialic acids is 9-O-acetylation, which has been implicated in sialoglycan recognition, ganglioside biology, and the survival and drug resistance of acute lymphoblastic leukaemia cells. Despite many functional implications, the molecular basis of 9-O-acetylation has remained elusive thus far. Following cellular approaches, including selective gene knockout by CRISPR/Cas genome editing, we here show that CASD1—a previously identified human candidate gene—is essential for sialic acid 9-O-acetylation. In vitro assays with the purified N-terminal luminal domain of CASD1 demonstrate transfer of acetyl groups from acetyl-coenzyme A to CMP-activated sialic acid and formation of a covalent acetyl-enzyme intermediate. Our study provides direct evidence that CASD1 is a sialate O-acetyltransferase and serves as key enzyme in the biosynthesis of 9-O-acetylated sialoglycans.",2015 Jul 14,"['Baumann, Anna-Maria T.', 'Bakkers, Mark J. G.', 'Buettner, Falk F. R.', 'Hartmann, Maike', 'Grove, Melanie', 'Langereis, Martijn A.', 'de Groot, Raoul J.', 'Mühlenhoff, Martina']",Nat Commun,,,True
25037be00789070e126164a9f939b64aeede0a64,PMC,9-O-Acetylation of sialic acids is catalysed by CASD1 via a covalent acetyl-enzyme intermediate,http://dx.doi.org/10.1038/ncomms8673,PMC4510713,26169044,CC BY,"Sialic acids, terminal sugars of glycoproteins and glycolipids, play important roles in development, cellular recognition processes and host–pathogen interactions. A common modification of sialic acids is 9-O-acetylation, which has been implicated in sialoglycan recognition, ganglioside biology, and the survival and drug resistance of acute lymphoblastic leukaemia cells. Despite many functional implications, the molecular basis of 9-O-acetylation has remained elusive thus far. Following cellular approaches, including selective gene knockout by CRISPR/Cas genome editing, we here show that CASD1—a previously identified human candidate gene—is essential for sialic acid 9-O-acetylation. In vitro assays with the purified N-terminal luminal domain of CASD1 demonstrate transfer of acetyl groups from acetyl-coenzyme A to CMP-activated sialic acid and formation of a covalent acetyl-enzyme intermediate. Our study provides direct evidence that CASD1 is a sialate O-acetyltransferase and serves as key enzyme in the biosynthesis of 9-O-acetylated sialoglycans.",2015 Jul 14,"['Baumann, Anna-Maria T.', 'Bakkers, Mark J. G.', 'Buettner, Falk F. R.', 'Hartmann, Maike', 'Grove, Melanie', 'Langereis, Martijn A.', 'de Groot, Raoul J.', 'Mühlenhoff, Martina']",Nat Commun,,,True
638c6b2e4772152a6cba52184c98dec9ca288c16,PMC,A case of bronchiolitis obliterans organizing pneumonia in an HIV-infected Korean patient successfully treated with clarithromycin,http://dx.doi.org/10.1186/s12879-015-1025-6,PMC4512086,26201392,CC BY,"BACKGROUND: Bronchiolitis obliterans organizing pneumonia (BOOP) is a type of diffuse interstitial lung disease characterized by the pathology of fibroblastic plugs in the lumens of the respiratory bronchioles, alveolar ducts, and alveoli. The occurrence of BOOP in human immunodeficiency virus (HIV)-infected patients has rarely been described, and there have been no clinical case reports in Korea. CASE PRESENTATION: A 24-year-old female who had been diagnosed with HIV ten years prior was admitted due to a 1-year history of cough and sputum production and a 3-day history of fever. She had poor adherence to anti-retroviral therapy (ART) due to gastrointestinal troubles. At the time of admission, her CD4 T-cell count was 5 cells/mm(3). A high resolution computed tomography (CT) scan showed tiny centrilobular nodules with a tree-in-bud pattern in both lungs. Bacterial culture, Pneumocystis jirovecii polymerase chain reaction (PCR), Aspergillus galactomannan antigen (Ag) assay, and respiratory virus PCR were negative. Rapid chest x-ray improvement was seen after a 7-day treatment with anti-tuberculosis medication, ceftriaxone, and clarithromycin. Miliary tuberculosis seemed unlikely considering the rapid radiologic improvement and negative tuberculosis PCR results. Due to the unknown etiology, we performed video-assisted thoracoscopic surgery (VATS) to determine the cause of the diffuse lung infiltration. Pathologic findings were consistent with BOOP, while tissue acid-fast bacilli (AFB) stain and tuberculosis PCR results were negative. Tuberculosis medication and intravenous ceftriaxone were discontinued, while treatment with clarithromycin monotherapy was sustained. Five months after discharge, the patient was asymptomatic with a normal chest x-ray and as her adherence to ART improved, her CD4 T-cell count rose to 181 cells/mm(3). Clarithromycin was discontinued at that time and the patient is currently receiving regular outpatient follow-up. CONCLUSION: This case suggests that macrolides are a potential treatment option in HIV-infected patients with mild BOOP. In cases that are otherwise unexplained or unresponsive to treatment, BOOP should be taken into consideration and surgical biopsy performed to confirm a diagnosis of BOOP.",2015 Jul 23,"['Jung, In Young', 'Jeon, Yong Duk', 'Ahn, Mi-young', 'Goag, Eunkyong', 'Lee, EunHye', 'Ahn, Hea Won', 'Ahn, Jin Young', 'Ku, Nam Su', 'Kim, June Myung', 'Choi, Jun Yong']",BMC Infect Dis,,,True
f475c055c4630c81ab519125a20ba96cd3e17e4a,PMC,Enhancing Human Immunodeficiency Virus-Specific CD8(+) T Cell Responses with Heteroclitic Peptides,http://dx.doi.org/10.3389/fimmu.2015.00377,PMC4512150,26257743,CC BY,"Human immunodeficiency virus (HIV)-specific CD8(+) T cells play a critical role in containing HIV replication and delaying disease progression. However, HIV-specific CD8(+) T cells become progressively more “exhausted” as chronic HIV infection proceeds. Symptoms of T cell exhaustion range from expression of inhibitory receptors and selective loss of cytokine production capacity through reduced proliferative potential, impaired differentiation into effector cells and increased susceptibility to apoptosis. While effective combination antiretroviral therapy (cART) durably reduces HIV viremia to undetectable levels, this alone does not restore the full pluripotency of HIV-specific CD8(+) T cells. In a number of studies, a subset of peptide epitope variants categorized as heteroclitic, restimulated more potent cellular immune responses in vitro than did the native, immunizing peptides themselves. This property of heteroclitic peptides has been exploited in experimental cancer and chronic viral infection models to promote clearance of transformed cells and persistent viruses. In this review, we consider the possibility that heteroclitic peptides could improve the efficacy of therapeutic vaccines as part of HIV immunotherapy or eradication strategies. We review literature on heteroclitic peptides and illustrate their potential to beneficially modulate the nature of HIV-specific T cell responses toward those found in the small minority of HIV-infected, aviremic cART-naïve persons termed elite controllers or long-term non-progressors. Our review suggests that the efficacy of HIV vaccines could be improved by identification, testing, and incorporation of heteroclitic variants of native HIV peptide epitopes.",2015 Jul 23,"['Adegoke, Adeolu Oyemade', 'Grant, Michael David']",Front Immunol,,,True
fd4b79d3d28a8c01c635987b474443590c240f4c,PMC,Macrophage Polarization in Virus-Host Interactions,http://dx.doi.org/10.4172/2155-9899.1000311,PMC4512304,26213635,CC BY,"Macrophage involvement in viral infections and antiviral states is common. However, this involvement has not been well-studied in the paradigm of macrophage polarization, which typically has been categorized by the dichotomy of classical (M1) and alternative (M2) statuses. Recent studies have revealed the complexity of macrophage polarization in response to various cellular mediators and exogenous stimuli by adopting a multipolar view to revisit the differential process of macrophages, especially those re-polarized during viral infections. Here, through examination of viral infections targeting macrophages/monocytic cells, we focus on the direct involvement of macrophage polarization during viral infections. Type I and type III interferons (IFNs) are critical in regulation of viral pathogenesis and host antiviral infection; thus, we propose to incorporate IFN-mediated antiviral states into the framework of macrophage polarization. This view is supported by the multifunctional properties of type I IFNs, which potentially elicit and regulate both M1- and M2-polarization in addition to inducing the antiviral state, and by the discoveries of viral mechanisms to adapt and modulate macrophage polarization. Indeed, several recent studies have demonstrated effective prevention of viral diseases through manipulation of macrophage immune statuses.",2015 Apr 27,"['Sang, Yongming', 'Miller, Laura C', 'Blecha, Frank']",J Clin Cell Immunol,,,True
52879771bf3fb8b982308b90d70bebd2485ceaf1,PMC,Sequence-independent characterization of viruses based on the pattern of viral small RNAs produced by the host,http://dx.doi.org/10.1093/nar/gkv587,PMC4513865,26040701,CC BY,"Virus surveillance in vector insects is potentially of great benefit to public health. Large-scale sequencing of small and long RNAs has previously been used to detect viruses, but without any formal comparison of different strategies. Furthermore, the identification of viral sequences largely depends on similarity searches against reference databases. Here, we developed a sequence-independent strategy based on virus-derived small RNAs produced by the host response, such as the RNA interference pathway. In insects, we compared sequences of small and long RNAs, demonstrating that viral sequences are enriched in the small RNA fraction. We also noted that the small RNA size profile is a unique signature for each virus and can be used to identify novel viral sequences without known relatives in reference databases. Using this strategy, we characterized six novel viruses in the viromes of laboratory fruit flies and wild populations of two insect vectors: mosquitoes and sandflies. We also show that the small RNA profile could be used to infer viral tropism for ovaries among other aspects of virus biology. Additionally, our results suggest that virus detection utilizing small RNAs can also be applied to vertebrates, although not as efficiently as to plants and insects.",2015 Jul 27,"['Aguiar, Eric\xa0Roberto\xa0Guimarães\xa0Rocha', 'Olmo, Roenick Proveti', 'Paro, Simona', 'Ferreira, Flavia Viana', 'de\xa0Faria, Isaque\xa0João\xa0da\xa0Silva', 'Todjro, Yaovi\xa0Mathias\xa0Honore', 'Lobo, Francisco Pereira', 'Kroon, Erna Geessien', 'Meignin, Carine', 'Gatherer, Derek', 'Imler, Jean-Luc', 'Marques, João Trindade']",Nucleic Acids Res,,,True
87cb1c3bdd1b8701c07a17f66a17e5d7a55797e5,PMC,Sequence-independent characterization of viruses based on the pattern of viral small RNAs produced by the host,http://dx.doi.org/10.1093/nar/gkv587,PMC4513865,26040701,CC BY,"Virus surveillance in vector insects is potentially of great benefit to public health. Large-scale sequencing of small and long RNAs has previously been used to detect viruses, but without any formal comparison of different strategies. Furthermore, the identification of viral sequences largely depends on similarity searches against reference databases. Here, we developed a sequence-independent strategy based on virus-derived small RNAs produced by the host response, such as the RNA interference pathway. In insects, we compared sequences of small and long RNAs, demonstrating that viral sequences are enriched in the small RNA fraction. We also noted that the small RNA size profile is a unique signature for each virus and can be used to identify novel viral sequences without known relatives in reference databases. Using this strategy, we characterized six novel viruses in the viromes of laboratory fruit flies and wild populations of two insect vectors: mosquitoes and sandflies. We also show that the small RNA profile could be used to infer viral tropism for ovaries among other aspects of virus biology. Additionally, our results suggest that virus detection utilizing small RNAs can also be applied to vertebrates, although not as efficiently as to plants and insects.",2015 Jul 27,"['Aguiar, Eric\xa0Roberto\xa0Guimarães\xa0Rocha', 'Olmo, Roenick Proveti', 'Paro, Simona', 'Ferreira, Flavia Viana', 'de\xa0Faria, Isaque\xa0João\xa0da\xa0Silva', 'Todjro, Yaovi\xa0Mathias\xa0Honore', 'Lobo, Francisco Pereira', 'Kroon, Erna Geessien', 'Meignin, Carine', 'Gatherer, Derek', 'Imler, Jean-Luc', 'Marques, João Trindade']",Nucleic Acids Res,,,True
0511ed1c3e91902ab662c81f8fc20c83a840e8d0,PMC,Risk factors for febrile respiratory illness and mono-viral infections in a semi-closed military environment: a case-control study,http://dx.doi.org/10.1186/s12879-015-1024-7,PMC4514976,26208494,CC BY,"BACKGROUND: Febrile respiratory illness (FRI) results in substantial burden in semi-closed environments. Tackling risk factors may reduce transmission and infection. However, risk factors involved in one setting may not be generalizable in all settings due to differences in climate, residential environment, population genetic and cultural backgrounds. This study aims to identify risk factors of FRI and mono-viral infections in a tropical military environment. METHODS: From year 2009 to 2012, military personnel with temperature ≥37.5 °C, cough and/or sore throat, and personnel with no fever or no respiratory symptoms were recruited as cases and controls, respectively. Subjects provided nasal wash specimens and answered a standardized questionnaire. Resplex assays were used to determine the viral etiologies. Descriptive, univariate and multivariate analyses of the variables were performed using appropriate descriptive tests and logistic regression modelling, respectively, with R program. RESULTS: A total of 7,743 FRI cases and 1,247 non-FRI study controls were recruited. Increasing age [adjusted odds ratio (AOR) = 1.03; 95 % confidence interval (CI) = 1.01-1.05], recruit camp (AOR = 4.67; 95 % CI = 3.99-5.46) and smoker (AOR = 1.31; 95 % CI = 1.13-1.52) were independent risk factors of FRI. Malay ethnicity was positively associated with influenza A(H1N1)pdm09 (AOR = 1.50; 95 % CI = 1.04-2.15) and coxsackie/echovirus (AOR = 1.67; 95 % CI = 1.19-2.36) mono-infection. Significant contact risk factors were stay-out personnel with ill household member (AOR = 4.96; 95 % CI = 3.39-7.24), and stay-in personnel with ill bunkmate and household member (AOR = 3.55; 95 % CI = 2.57-4.91). Staying in camp with none ill in bunk and at home was a protective factor against FRI (AOR = 0.80; 95 % CI = 0.64-0.99). These contact risk factors were similarly observed for the five most common viruses detected, namely adenovirus, rhinoviruses, influenza A and B, and coxsackie/echovirus. CONCLUSION: Increasing age, smoker, recruit-camp, stay-out personnel with ill household members and stay-in personnel with ill bunkmates were independent risk factors of FRI in a semi-closed military environment. Early identification and isolation of ill personnel from their bunk may be effective to prevent and reduce transmission and disease burden.",2015 Jul 25,"['Pang, Junxiong', 'Jin, Jing', 'Loh, Jin Phang', 'Tan, Boon Huan', 'Koh, Wee Hong Victor', 'Ng, Sock Hoon', 'Ho, Zheng Jie Marc', 'Gao, Qiuhan', 'Cook, Alex R', 'Hsu, Li Yang', 'Lee, Vernon J', 'Chen, Mark I Cheng']",BMC Infect Dis,,,True
8da1231a64d73bc59f2af993bf1a2466265ffa4a,PMC,Phylogenetic and recombination analysis of Tobacco bushy top virus in China,http://dx.doi.org/10.1186/s12985-015-0340-2,PMC4514990,26209518,CC BY,"BACKGROUND: During the past decade, tobacco bushy top disease, which is mainly caused by a combination of Tobacco bushy top virus (TBTV) and Tobacco vein-distorting virus (TVDV), underwent a sudden appearance, extreme virulence and degeneration of the epidemic in the Yunnan province of China. In addition to integrative control of its aphid vector, it is of interest to examine diversity and evolution among different TBTV isolates. METHODS: 5’ and 3’ RACE, combined with one step full-length RT-PCR, were used to clone the full-length genome of three new isolates of TBTV that exhibited mild pathogenicity in Chinese fields. Nucleotide and amino acid sequences for the TBTV isolates were analyzed by DNAMAN. MEGA 5.0 was used to construct phylogenetic trees. RDP4 was used to detect recombination events during evolution of these isolates. RESULTS: The genomes of three isolates, termed TBTV-JC, TBTV-MD-I and TBTV-MD-II, were 4152 nt in length and included one distinctive difference from previously reported TBTV isolates: the first nucleotide of the genome was a guanylate instead of an adenylate. Diversity and phylogenetic analyses among these three new TBTV isolates and five other available isolates suggest that ORFs and 3’UTRs of TBTV may have evolved separately. Moreover, the RdRp-coding region was the most variable. Recombination analysis detected a total of 29 recombination events in the 8 TBTV isolates, in which 24 events are highly likely and 5 events have low-level likelihood based on their correlation with the phylogenetic trees. The three new TBTV isolates have individual recombination patterns with subtle divergences in parents and locations. CONCLUSIONS: The genome sizes of TBTV isolates were constant while different ORF-coding regions and 3’UTRs may have evolved separately. The RdRp-coding region was the most variable. Frequent recombination occurred among TBTV isolates. Three new TBTV isolates have individual recombination patterns and may have different progenitors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0340-2) contains supplementary material, which is available to authorized users.",2015 Jul 25,"['Wang, Deya', 'Yu, Chengming', 'Wang, Guolu', 'Shi, Kerong', 'Li, Fan', 'Yuan, Xuefeng']",Virol J,,,True
fb113c8235675412d874b092faf5b997ac410434,PMC,Acute phase proteins as local biomarkers of respiratory infection in calves,http://dx.doi.org/10.1186/s12917-015-0485-7,PMC4515006,26209015,CC BY,"BACKGROUND: Cumulating reports suggest that acute phase proteins (APPs) do not only play a role as systemic inflammatory mediators, but are also expressed in different tissues as local reaction to inflammatory stimuli. The present study aimed to evaluate presence and changes in luminal lung concentrations of the APPs haptoglobin (Hp), lipopolysaccharide binding protein (LBP), C-reactive protein (CRP), and lactoferrin (Lf) in calves with an acute respiratory disease experimentally induced by Chlamydia (C.) psittaci. RESULTS: Intra-bronchial inoculation of the pathogen resulted in a consistent respiratory illness. In venous blood of the infected calves (n = 13), concentrations of plasma proteins and serum LBP were assessed (i) before exposure and (ii) 8 times within 14 days after inoculation (dpi). Increasing clinical illness correlated significantly with increasing LBP—and decreasing albumin concentrations in blood, both verifying a systemic acute phase response. Broncho-alveolar lavage fluid (BALF) was obtained from all 13 calves experimentally infected with C. psittaci at 4, 9 and 14 dpi, and from 6 uninfected healthy calves. Concentrations of bovine serum albumin (BSA), Hp, LBP, CRP and Lf in BALF were determined by ELISA. In infected animals, absolute concentrations of LBP and Hp in BALF correlated significantly with the respiratory score. The quotient [LBP]/[BSA] in BALF peaked significantly in acutely infected animals (4 dpi), showed a time-dependent decrease during the recovery phase (9-14 dpi), and was significantly higher compared to healthy controls. Concentrations of Hp and Lf in BALF as well as [Hp]/[BSA]—and [Lf]/[BSA]-quotients decreased during the study in infected animals, but were never higher than in healthy controls. CRP concentrations and [CRP]/[BSA]-quotient did not express significant differences between infected and healthy animals or during the course of infection. CONCLUSION: In conclusion, absolute concentrations of LBP in blood and BALF as well as the quotient [LBP]/[BSA] in BALF perfectly paralleled the clinical course of respiratory illness after infection. Beside LBP, the suitability of Hp and Lf as local biomarkers of respiratory infections in cattle and their role in the local response to pathogens is worth further investigation, while CRP does not seem to play a role in local defense mechanisms of the bovine lung.",2015 Jul 25,"['Prohl, Annette', 'Schroedl, Wieland', 'Rhode, Heidrun', 'Reinhold, Petra']",BMC Vet Res,,,True
dbbb49ef360b3f97d6ecda042ef75186a78ddfa3,PMC,Risk assessment as a tool for improving external biosecurity at farm level,http://dx.doi.org/10.1186/s12917-015-0477-7,PMC4515931,26215281,CC BY,"BACKGROUND: Biosecurity routines at herd level may reduce the probability of introduction of disease into the herd, but some measures may be regarded as expensive and cumbersome for the farmers. Custom-made measures based on individual farm characteristics may aid in improving the actual application of on-farm biosecurity. The aim of the study was to provide a tool for calculating the effects of different biosecurity measures and strategies on the individual farm level. A simple model was developed to assess the risk of disease introduction and the need for biosecurity measures in individual farms. To illustrate the general applicability of the tool, it was applied to theoretical examples of Swedish cattle and pig farms and diseases endemic in those animal species in the EU, in two scenarios with different between-farm contact patterns. RESULTS: The model illustrated that the most important factors affecting the risk, and the effect of biosecurity measures such as quarantine routines and protective clothing, were the frequency of between-farm contacts and prevalence of the disease. The risk of introduction as well as the effect of biosecurity measures differed between farm types and disease transmission routes. Adapting contact patterns to mitigate a specific disease risk was as important as biosecurity measures for some farm types, but the largest effect was seen when combining biosecurity measures with more planned contact patterns. CONCLUSIONS: The risk assessment model proved useful for illustrating the risk of introduction of endemic diseases and the mitigating effect of different biosecurity measures on farm level. Model outputs could be used to justify prioritisation of measures or adapting contact patterns. The theoretic exercise of adjusting model inputs and comparing outputs may help veterinary advisors to understand farm-specific risks and motivate farmers to improve biosecurity in their individual farm, as it can be tailored to each farmer’s needs and preferences.",2015 Jul 28,"['Lewerin, Susanna Sternberg', 'Österberg, Julia', 'Alenius, Stefan', 'Elvander, Marianne', 'Fellström, Claes', 'Tråvén, Madeleine', 'Wallgren, Per', 'Waller, Karin Persson', 'Jacobson, Magdalena']",BMC Vet Res,,,True
6e94aa9c37dd7be5b553090717c59992005d114b,PMC,Identification of Glial Activation Markers by Comparison of Transcriptome Changes between Astrocytes and Microglia following Innate Immune Stimulation,http://dx.doi.org/10.1371/journal.pone.0127336,PMC4516330,26214311,CC0,"The activation of astrocytes and microglia is often associated with diseases of the central nervous system (CNS). Understanding how activation alters the transcriptome of these cells may offer valuable insight regarding how activation of these cells mediate neurological damage. Furthermore, identifying common and unique pathways of gene expression during activation may provide new insight into the distinct roles these cells have in the CNS during infection and inflammation. Since recent studies indicate that TLR7 recognizes not only viral RNA but also microRNAs that are released by damaged neurons and elevated during neurological diseases, we first examined the response of glial cells to TLR7 stimulation using microarray analysis. Microglia were found to generate a much stronger response to TLR7 activation than astrocytes, both in the number of genes induced as well as fold induction. Although the primary pathways induced by both cell types were directly linked to immune responses, microglia also induced pathways associated with cellular proliferation, while astrocytes did not. Targeted analysis of a subset of the upregulated genes identified unique mRNA, including Ifi202b which was only upregulated by microglia and was found to be induced during both retroviral and bunyavirus infections in the CNS. In addition, other genes including Birc3 and Gpr84 as well as two expressed sequences AW112010 and BC023105 were found to be induced in both microglia and astrocytes and were upregulated in the CNS following virus infection. Thus, expression of these genes may a useful measurement of glial activation during insult or injury to the CNS.",2015 Jul 27,"['Madeddu, Silvia', 'Woods, Tyson A.', 'Mukherjee, Piyali', 'Sturdevant, Dan', 'Butchi, Niranjan B.', 'Peterson, Karin E.']",PLoS One,,,True
ac1d4ff87c5d0b09e2b5a1e798c7c8ed4d8796cb,PMC,Identification of Glial Activation Markers by Comparison of Transcriptome Changes between Astrocytes and Microglia following Innate Immune Stimulation,http://dx.doi.org/10.1371/journal.pone.0127336,PMC4516330,26214311,CC0,"The activation of astrocytes and microglia is often associated with diseases of the central nervous system (CNS). Understanding how activation alters the transcriptome of these cells may offer valuable insight regarding how activation of these cells mediate neurological damage. Furthermore, identifying common and unique pathways of gene expression during activation may provide new insight into the distinct roles these cells have in the CNS during infection and inflammation. Since recent studies indicate that TLR7 recognizes not only viral RNA but also microRNAs that are released by damaged neurons and elevated during neurological diseases, we first examined the response of glial cells to TLR7 stimulation using microarray analysis. Microglia were found to generate a much stronger response to TLR7 activation than astrocytes, both in the number of genes induced as well as fold induction. Although the primary pathways induced by both cell types were directly linked to immune responses, microglia also induced pathways associated with cellular proliferation, while astrocytes did not. Targeted analysis of a subset of the upregulated genes identified unique mRNA, including Ifi202b which was only upregulated by microglia and was found to be induced during both retroviral and bunyavirus infections in the CNS. In addition, other genes including Birc3 and Gpr84 as well as two expressed sequences AW112010 and BC023105 were found to be induced in both microglia and astrocytes and were upregulated in the CNS following virus infection. Thus, expression of these genes may a useful measurement of glial activation during insult or injury to the CNS.",2015 Jul 27,"['Madeddu, Silvia', 'Woods, Tyson A.', 'Mukherjee, Piyali', 'Sturdevant, Dan', 'Butchi, Niranjan B.', 'Peterson, Karin E.']",PLoS One,,,False
d2057831023248265b009ed7fb7710123c69feaa,PMC,"Viroporins, Examples of the Two-Stage Membrane Protein Folding Model",http://dx.doi.org/10.3390/v7072781,PMC4517110,26131957,CC BY,"Viroporins are small, α-helical, hydrophobic virus encoded proteins, engineered to form homo-oligomeric hydrophilic pores in the host membrane. Viroporins participate in multiple steps of the viral life cycle, from entry to budding. As any other membrane protein, viroporins have to find the way to bury their hydrophobic regions into the lipid bilayer. Once within the membrane, the hydrophobic helices of viroporins interact with each other to form higher ordered structures required to correctly perform their porating activities. This two-step process resembles the two-stage model proposed for membrane protein folding by Engelman and Poppot. In this review we use the membrane protein folding model as a leading thread to analyze the mechanism and forces behind the membrane insertion and folding of viroporins. We start by describing the transmembrane segment architecture of viroporins, including the number and sequence characteristics of their membrane-spanning domains. Next, we connect the differences found among viroporin families to their viral genome organization, and finalize focusing on the pathways used by viroporins in their way to the membrane and on the transmembrane helix-helix interactions required to achieve proper folding and assembly.",2015 Jun 26,"['Martinez-Gil, Luis', 'Mingarro, Ismael']",Viruses,,,True
1986e96f2be6bd012fcd4d0b731caf62c7a4dea2,PMC,Relevance of Viroporin Ion Channel Activity on Viral Replication and Pathogenesis,http://dx.doi.org/10.3390/v7072786,PMC4517115,26151305,CC BY,"Modification of host-cell ionic content is a significant issue for viruses, as several viral proteins displaying ion channel activity, named viroporins, have been identified. Viroporins interact with different cellular membranes and self-assemble forming ion conductive pores. In general, these channels display mild ion selectivity, and, eventually, membrane lipids play key structural and functional roles in the pore. Viroporins stimulate virus production through different mechanisms, and ion channel conductivity has been proved particularly relevant in several cases. Key stages of the viral cycle such as virus uncoating, transport and maturation are ion-influenced processes in many viral species. Besides boosting virus propagation, viroporins have also been associated with pathogenesis. Linking pathogenesis either to the ion conductivity or to other functions of viroporins has been elusive for a long time. This article summarizes novel pathways leading to disease stimulated by viroporin ion conduction, such as inflammasome driven immunopathology.",2015 Jul 3,"['Nieto-Torres, Jose L.', 'Verdiá-Báguena, Carmina', 'Castaño-Rodriguez, Carlos', 'Aguilella, Vicente M.', 'Enjuanes, Luis']",Viruses,,,True
ae3d16cad153ad376ec5782d74688a6f93093c37,PMC,Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses,http://dx.doi.org/10.3390/v7072794,PMC4517123,26198243,CC BY,"Interferon (IFN) treatment induces the expression of hundreds of IFN-stimulated genes (ISGs). However, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play a role in mediating the antiviral response in vivo using gene knockout mouse models. IFNs inhibit rhabdovirus  replication at different stages via the induction of a variety of ISGs. This review will discuss how individual ISG products confer resistance to rhabdoviruses by blocking viral entry, degrading single stranded viral RNA, inhibiting viral translation or preventing release of virions from the cell. Furthermore, this review will highlight how these viruses counteract the host IFN system.",2015 Jul 7,"['Blondel, Danielle', 'Maarifi, Ghizlane', 'Nisole, Sébastien', 'Chelbi-Alix, Mounira K.']",Viruses,,,True
adeed4609c727b1be5175cb36f7032a6337c89b3,PMC,Learning from Ebola Virus: How to Prevent Future Epidemics,http://dx.doi.org/10.3390/v7072797,PMC4517126,26184283,CC BY,"The recent Ebola virus disease (EVD) epidemic in Guinea, Liberia and Sierra Leone demonstrated that the World Health Organization (WHO) is incapable to control outbreaks of infectious diseases in less developed regions of the world. This essay analyses the causes for the failure of the international response and proposes four measures to improve resilience, early detection and response to future outbreaks of infectious diseases.",2015 Jul 9,"Kekulé, Alexander S.",Viruses,,,False
8e2bd29ae5f88af72cf04f8e7da51a3eb9c8258f,PMC,Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes,http://dx.doi.org/10.3390/v7072812,PMC4517141,26197333,CC BY,"Dengue virus (DENV) is an important human pathogen causing millions of disease cases and thousands of deaths worldwide. Non-structural protein 4A (NS4A) is a vital component of the viral replication complex (RC) and plays a major role in the formation of host cell membrane-derived structures that provide a scaffold for replication. The N-terminal cytoplasmic region of NS4A(1–48) is known to preferentially interact with highly curved membranes. Here, we provide experimental evidence for the stable binding of NS4A(1–48) to small liposomes using a liposome floatation assay and identify the lipid binding sequence by NMR spectroscopy. Mutations L6E;M10E were previously shown to inhibit DENV replication and to interfere with the binding of NS4A(1–48) to small liposomes. Our results provide new details on the interaction of the N-terminal region of NS4A with membranes and will prompt studies of the functional relevance of the curvature sensitive membrane anchor at the N-terminus of NS4A.",2015 Jul 21,"['Hung, Yu-Fu', 'Schwarten, Melanie', 'Hoffmann, Silke', 'Willbold, Dieter', 'Sklan, Ella H.', 'Koenig, Bernd W.']",Viruses,,,True
902feae616d8f0ffb508ef3a4a1fbc344bb63133,PMC,Antibody response of definitive hosts against antigens of two life stages of the neuropathogenic schistosome Trichobilharzia regenti,http://dx.doi.org/10.1186/s13071-015-1007-y,PMC4517386,26216102,CC BY,"BACKGROUND: The nasal avian schistosome Trichobilharzia regenti spends part of its intravertebrate period of life within the central nervous system. Migration of the parasites can be accompanied by neuromotor disorders or paralysis in natural definitive hosts (ducks) and even in laboratory mammals. Cercariae are also able to penetrate human skin and induce cercarial dermatitis. While the cellular and antibody responses against cercariae and migrating schistosomula have been investigated in mice, little is known about immune reactions in birds. This study first describes the dynamics of antibody response in infected ducks and identifies frequently recognized antigens that may serve as diagnostic markers of infection by T. regenti. METHODS: Groups of 35 domestic ducks and 10 mallards were exposed to different doses of T. regenti cercariae. Sera were collected at predefined time intervals and tested by ELISA for the presence of specific anti-cercarial IgY and IgM. Antigens recognized by the antibodies were identified on Western blots of cercariae and schistosomula. The applicability in immunodiagnostics was statistically evaluated by expression of specificity and sensitivity values for individual antigens. RESULTS: In ELISA, the levels of anti-cercarial IgM peaked on day 15 pi. Increased production of IgY associated with the later phases of infection was observed in most individuals around 20 dpi and culminated 30 dpi. The time course of antibody response did not differ among experimental groups, variations were only observed in the levels of specific IgY which depended rather on the age of ducks at the time of infection than on the infectious dose. On Western blots, 40 cercarial and 7 schistosomular antigens were recognized by IgY from infected ducks. Among them, 4 cercarial antigens of 50, 47, 32 and 19 kDa provided the most sensitive and specific reactions. CONCLUSIONS: Antigens of cercariae and schistosomula elicited distinct antibody response in ducks, which correlated positively with the age of animals at the time of infection. Several antigens originating in cercariae and fewer in schistosomula were recognized by IgY with diverse sensitivity and specificity; only a few seemed to be common to both stages. Four of them were considered as the most promising candidates for immunodiagnostics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-1007-y) contains supplementary material, which is available to authorized users.",2015 Jul 28,"['Turjanicová, Libuše', 'Mikeš, Libor', 'Pecková, Monika', 'Horák, Petr']",Parasit Vectors,,,True
b79e0dae232a80e5e92f12110cc4df835c171518,PMC,Representing virus-host interactions and other multi-organism processes in the Gene Ontology,http://dx.doi.org/10.1186/s12866-015-0481-x,PMC4517558,26215368,CC BY,"BACKGROUND: The Gene Ontology project is a collaborative effort to provide descriptions of gene products in a consistent and computable language, and in a species-independent manner. The Gene Ontology is designed to be applicable to all organisms but up to now has been largely under-utilized for prokaryotes and viruses, in part because of a lack of appropriate ontology terms. METHODS: To address this issue, we have developed a set of Gene Ontology classes that are applicable to microbes and their hosts, improving both coverage and quality in this area of the Gene Ontology. Describing microbial and viral gene products brings with it the additional challenge of capturing both the host and the microbe. Recognising this, we have worked closely with annotation groups to test and optimize the GO classes, and we describe here a set of annotation guidelines that allow the controlled description of two interacting organisms. CONCLUSIONS: Building on the microbial resources already in existence such as ViralZone, UniProtKB keywords and MeGO, this project provides an integrated ontology to describe interactions between microbial species and their hosts, with mappings to the external resources above. Housing this information within the freely-accessible Gene Ontology project allows the classes and annotation structure to be utilized by a large community of biologists and users.",2015 Jul 28,"['Foulger, R. E.', 'Osumi-Sutherland, D.', 'McIntosh, B. K.', 'Hulo, C.', 'Masson, P.', 'Poux, S.', 'Le Mercier, P.', 'Lomax, J.']",BMC Microbiol,,,True
e642816c09dd07b7bdf515088670a72ee8698bd8,PMC,Pulmonary Function and Clinical Manifestations of Patients Infected with Mild Influenza A Virus Subtype H1N1: A One-Year Follow-Up,http://dx.doi.org/10.1371/journal.pone.0133698,PMC4517883,26218647,CC BY,"OBJECTIVE: To investigate the long-term effects of mild H1N1 influenza infection on the pulmonary function of a cohort of patients. METHODS: Forty-eight patients, all diagnosed with influenza A virus subtype H1N1 in 2009, were retrospectively included in this study. Each patient in the study was monitored for 11-13 months by standard pulmonary function examination. The examination included monitoring respiratory tract infection symptoms (cough, expectoration or gasping) and vital signs. Long-term changes in symptoms and changes in vital signs were correlated back to and compared with the severity of the initial H1N1 influenza infection. RESULTS: One year post discharge, mild to moderate pulmonary dysfunction was observed in the majority of patients. Further, 54.2% of patients had signs of severe abnormal pulmonary function, including diffusion disorder (33.3%) and small airway dysfunction (33.3%). Fourteen patients presented with respiratory tract infection symptoms; 12 with abnormal pulmonary function and two with normal pulmonary function. Our results indicated that the change in pulmonary function at one year post discharge was not significantly correlated with the severity of H1N1 influenza. CONCLUSION: Signs and symptoms of abnormal pulmonary function accompanied by respiratory tract infection symptoms remain for some patients after one year following discharge from the hospital for mild influenza A virus subtype H1N1 infection. These patients should continue to be monitored for any changes in condition and symptoms and rehabilitation treatment should be provided when necessary.",2015 Jul 28,"['Liu, Wei', 'Peng, Liping', 'Liu, Hongmei', 'Hua, Shucheng']",PLoS One,,,True
f58cfab11be3906401550ffe0ba6e444d1056853,PMC,Human Enterovirus Nonstructural Protein 2C(ATPase) Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone,http://dx.doi.org/10.1371/journal.ppat.1005067,PMC4517893,26218680,CC BY,"RNA helicases and chaperones are the two major classes of RNA remodeling proteins, which function to remodel RNA structures and/or RNA-protein interactions, and are required for all aspects of RNA metabolism. Although some virus-encoded RNA helicases/chaperones have been predicted or identified, their RNA remodeling activities in vitro and functions in the viral life cycle remain largely elusive. Enteroviruses are a large group of positive-stranded RNA viruses in the Picornaviridae family, which includes numerous important human pathogens. Herein, we report that the nonstructural protein 2C(ATPase) of enterovirus 71 (EV71), which is the major causative pathogen of hand-foot-and-mouth disease and has been regarded as the most important neurotropic enterovirus after poliovirus eradication, functions not only as an RNA helicase that 3′-to-5′ unwinds RNA helices in an adenosine triphosphate (ATP)-dependent manner, but also as an RNA chaperone that destabilizes helices bidirectionally and facilitates strand annealing and complex RNA structure formation independently of ATP. We also determined that the helicase activity is based on the EV71 2C(ATPase) middle domain, whereas the C-terminus is indispensable for its RNA chaperoning activity. By promoting RNA template recycling, 2C(ATPase) facilitated EV71 RNA synthesis in vitro; when 2C(ATPase) helicase activity was impaired, EV71 RNA replication and virion production were mostly abolished in cells, indicating that 2C(ATPase)-mediated RNA remodeling plays a critical role in the enteroviral life cycle. Furthermore, the RNA helicase and chaperoning activities of 2C(ATPase) are also conserved in coxsackie A virus 16 (CAV16), another important enterovirus. Altogether, our findings are the first to demonstrate the RNA helicase and chaperoning activities associated with enterovirus 2C(ATPase), and our study provides both in vitro and cellular evidence for their potential roles during viral RNA replication. These findings increase our understanding of enteroviruses and the two types of RNA remodeling activities.",2015 Jul 28,"['Xia, Hongjie', 'Wang, Peipei', 'Wang, Guang-Chuan', 'Yang, Jie', 'Sun, Xianlin', 'Wu, Wenzhe', 'Qiu, Yang', 'Shu, Ting', 'Zhao, Xiaolu', 'Yin, Lei', 'Qin, Cheng-Feng', 'Hu, Yuanyang', 'Zhou, Xi']",PLoS Pathog,,,True
2cd037e5b6e8f285b0a68b5d10c627d407046c0e,PMC,Ebola Virus Disease: Experience and Decision Making for the First Patients outside of Africa,http://dx.doi.org/10.1371/journal.pmed.1001857,PMC4517924,26218574,CC BY,David Stephens and colleagues describe their experience of treating patients with Ebola virus disease at Emory University in the United States.,2015 Jul 28,"['Stephens, David S.', 'Ribner, Bruce S.', 'Gartland, Bryce D.', 'Feistritzer, Nancye R.', 'Farley, Monica M.', 'Larsen, Christian P.', 'Fox, John T.']",PLoS Med,,,True
0d1d976e7073e6c1bbc69805f5c61a2f8607c911,PMC,Inhibitory effect of Phyllanthus urinaria L. extract on the replication of lamivudine-resistant hepatitis B virus in vitro,http://dx.doi.org/10.1186/s12906-015-0792-3,PMC4518506,26220282,CC BY,"BACKGROUND: Long-term treatment of chronic hepatitis B (CHB) with nucleos(t)ide analogs results in the emergence of drug-resistant hepatitis B virus (HBV) harboring mutations in the polymerase (P) gene. The Phyllanthus extract has anti-HBV activity; however, its antiviral activity against lamivudine (LMV)-resistant mutants has not been examined. METHODS: HBV harboring LMV-resistant mutations (rtM204I, rtM204V, and rtM204S) in the P gene at the YMDD ((203)tyrosine-methionine-aspartate-aspartate(206)) reverse transcriptase (RT) active site were generated and their sensitivity to Phyllanthus urinaria koreanis extract examined. Southern blotting and real-time PCR were used to determine the concentration of plant extract required to inhibit HBV DNA synthesis by 50 and 90 % (EC(50) and EC(90), respectively). An enzyme-linked immunosorbent assay was used to measure the EC(50) of HBV surface antigen (HBsAg) and HBV core antigen (HBcAg) secretion, and the 50 % cytotoxic concentration of the extract was measured in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Real-time RT-PCR was used to measure mRNA expression levels. RESULTS: The expression of intracellular HBV DNAs in HBV WT- or mutant-transfected HepG2 cells decreased upon treatment with Phyllanthus extract. The secretion of HBsAg and HBcAg also fell in a dose-dependent manner. Phyllanthus extract induced interferon-beta (IFN-β), cyclooxygenase-2 (COX-2), and interleukin-6 (IL-6) mRNA expression in HBV WT-transfected HepG2 cells, possibly via activation of extracellular signal-regulated kinases and c-jun N-terminal kinases and the induction of retinoic acid inducible gene-I, toll-like receptor 3, myeloid differentiation primary response gene 88, and/or tumor necrosis factor receptor-associated factor 6 gene expression. HBV transfection in the absence of extract or exposure of cells to extract alone did not trigger these signaling cascades. CONCLUSIONS: Phyllanthus extract inhibited HBV DNA synthesis and HBsAg and HBcAg secretion by replicating cells harboring HBV wild-type and LMV-resistant mutants, likely by inducing the expression of IFN-β, COX-2, and IL-6. These data indicate that Phyllanthus extract may be useful as an alternative therapeutic agent for the treatment of drug-resistant CHB patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12906-015-0792-3) contains supplementary material, which is available to authorized users.",2015 Jul 29,"['Jung, Jaesung', 'Kim, Nam Keun', 'Park, Sun', 'Shin, Ho-Joon', 'Hwang, Seong Gyu', 'Kim, Kyongmin']",BMC Complement Altern Med,,,True
d37ad55db18a412c55ca07e3780ab65ec8040908,PMC,"An Overview of Practical Applications of Protein Disorder Prediction and Drive for Faster, More Accurate Predictions",http://dx.doi.org/10.3390/ijms160715384,PMC4519904,26198229,CC BY,"Protein disordered regions are segments of a protein chain that do not adopt a stable structure. Thus far, a variety of protein disorder prediction methods have been developed and have been widely used, not only in traditional bioinformatics domains, including protein structure prediction, protein structure determination and function annotation, but also in many other biomedical fields. The relationship between intrinsically-disordered proteins and some human diseases has played a significant role in disorder prediction in disease identification and epidemiological investigations. Disordered proteins can also serve as potential targets for drug discovery with an emphasis on the disordered-to-ordered transition in the disordered binding regions, and this has led to substantial research in drug discovery or design based on protein disordered region prediction. Furthermore, protein disorder prediction has also been applied to healthcare by predicting the disease risk of mutations in patients and studying the mechanistic basis of diseases. As the applications of disorder prediction increase, so too does the need to make quick and accurate predictions. To fill this need, we also present a new approach to predict protein residue disorder using wide sequence windows that is applicable on the genomic scale.",2015 Jul 7,"['Deng, Xin', 'Gumm, Jordan', 'Karki, Suman', 'Eickholt, Jesse', 'Cheng, Jianlin']",Int J Mol Sci,,,True
30d069a3931b607b8f5c3b7b2556e78f2cd9b4e3,PMC,The CCR5Δ32 (rs333) polymorphism is not a predisposing factor for severe pandemic influenza in the Brazilian admixed population,http://dx.doi.org/10.1186/s13104-015-1299-1,PMC4520097,26223981,CC BY,"BACKGROUND: Recent studies have tried to identify host genetic variants that could explain severe cases and deaths in infection with Influenza A(H1N1)pdm09, especially among children and young adults. CCR5 is a chemokine receptor expressed on T cells, macrophages and dendritic cells, which is an important mediator of leukocyte chemotaxis during the immune response. A deletion mutation (Δ32) in this gene interferes with the response of immune cells, impairing viral clearance. We evaluated the CCR5Δ32 polymorphism (rs333) in individuals of the Brazilian admixed population with a diagnosis of Influenza A(H1N1)pdm09 infection. METHODS: A total of 330 subjects with a diagnosis of Influenza A(H1N1)pdm09, evaluated at health services in the northern and northeastern regions of Brazil between June 2009 and August 2010, were genotyped for the Δ32 deletion (rs333). The cases were classified according to the progression of infection into a group of hospitalized patients (n = 156) and a group of non-hospitalized patients (n = 174). RESULTS: No significant differences in the allele or genotype frequencies of the CCR5Δ32 polymorphism were observed between non-hospitalized and hospitalized patients (p = 0.289 and p = 0.431, respectively). CONCLUSION: The Δ32 deletion in the CCR5 gene is not associated with an unfavorable outcome in patients infected with Influenza A(H1N1)pdm09 in the Brazilian admixed population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13104-015-1299-1) contains supplementary material, which is available to authorized users.",2015 Jul 30,"['Maestri, Alvino', 'dos Santos, Mirleide Cordeiro', 'Ribeiro-Rodrigues, Elzemar M', 'de Mello, Wyller Alencar', 'Sousa, Rita Catarina Medeiros', 'dos Santos, Sidney Emanuel', 'Sortica, Vinicius Albuquerque']",BMC Res Notes,,,False
1f16c5e424d5b436085329d94649118ac319e748,PMC,The CCR5Δ32 (rs333) polymorphism is not a predisposing factor for severe pandemic influenza in the Brazilian admixed population,http://dx.doi.org/10.1186/s13104-015-1299-1,PMC4520097,26223981,CC BY,"BACKGROUND: Recent studies have tried to identify host genetic variants that could explain severe cases and deaths in infection with Influenza A(H1N1)pdm09, especially among children and young adults. CCR5 is a chemokine receptor expressed on T cells, macrophages and dendritic cells, which is an important mediator of leukocyte chemotaxis during the immune response. A deletion mutation (Δ32) in this gene interferes with the response of immune cells, impairing viral clearance. We evaluated the CCR5Δ32 polymorphism (rs333) in individuals of the Brazilian admixed population with a diagnosis of Influenza A(H1N1)pdm09 infection. METHODS: A total of 330 subjects with a diagnosis of Influenza A(H1N1)pdm09, evaluated at health services in the northern and northeastern regions of Brazil between June 2009 and August 2010, were genotyped for the Δ32 deletion (rs333). The cases were classified according to the progression of infection into a group of hospitalized patients (n = 156) and a group of non-hospitalized patients (n = 174). RESULTS: No significant differences in the allele or genotype frequencies of the CCR5Δ32 polymorphism were observed between non-hospitalized and hospitalized patients (p = 0.289 and p = 0.431, respectively). CONCLUSION: The Δ32 deletion in the CCR5 gene is not associated with an unfavorable outcome in patients infected with Influenza A(H1N1)pdm09 in the Brazilian admixed population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13104-015-1299-1) contains supplementary material, which is available to authorized users.",2015 Jul 30,"['Maestri, Alvino', 'dos Santos, Mirleide Cordeiro', 'Ribeiro-Rodrigues, Elzemar M', 'de Mello, Wyller Alencar', 'Sousa, Rita Catarina Medeiros', 'dos Santos, Sidney Emanuel', 'Sortica, Vinicius Albuquerque']",BMC Res Notes,,,False
87e6ba2c7e5748b172c7530dbb9e8a040e74a719,PMC,The CCR5Δ32 (rs333) polymorphism is not a predisposing factor for severe pandemic influenza in the Brazilian admixed population,http://dx.doi.org/10.1186/s13104-015-1299-1,PMC4520097,26223981,CC BY,"BACKGROUND: Recent studies have tried to identify host genetic variants that could explain severe cases and deaths in infection with Influenza A(H1N1)pdm09, especially among children and young adults. CCR5 is a chemokine receptor expressed on T cells, macrophages and dendritic cells, which is an important mediator of leukocyte chemotaxis during the immune response. A deletion mutation (Δ32) in this gene interferes with the response of immune cells, impairing viral clearance. We evaluated the CCR5Δ32 polymorphism (rs333) in individuals of the Brazilian admixed population with a diagnosis of Influenza A(H1N1)pdm09 infection. METHODS: A total of 330 subjects with a diagnosis of Influenza A(H1N1)pdm09, evaluated at health services in the northern and northeastern regions of Brazil between June 2009 and August 2010, were genotyped for the Δ32 deletion (rs333). The cases were classified according to the progression of infection into a group of hospitalized patients (n = 156) and a group of non-hospitalized patients (n = 174). RESULTS: No significant differences in the allele or genotype frequencies of the CCR5Δ32 polymorphism were observed between non-hospitalized and hospitalized patients (p = 0.289 and p = 0.431, respectively). CONCLUSION: The Δ32 deletion in the CCR5 gene is not associated with an unfavorable outcome in patients infected with Influenza A(H1N1)pdm09 in the Brazilian admixed population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13104-015-1299-1) contains supplementary material, which is available to authorized users.",2015 Jul 30,"['Maestri, Alvino', 'dos Santos, Mirleide Cordeiro', 'Ribeiro-Rodrigues, Elzemar M', 'de Mello, Wyller Alencar', 'Sousa, Rita Catarina Medeiros', 'dos Santos, Sidney Emanuel', 'Sortica, Vinicius Albuquerque']",BMC Res Notes,,,True
e6a4aa79206219f2e1229c6ecc507078520466b0,PMC,Membrane-Active Sequences within gp41 Membrane Proximal External Region (MPER) Modulate MPER-Containing Peptidyl Fusion Inhibitor Activity and the Biosynthesis of HIV-1 Structural Proteins,http://dx.doi.org/10.1371/journal.pone.0134851,PMC4521866,26230322,CC BY,"The membrane proximal external region (MPER) is a highly conserved membrane-active region located at the juxtamembrane positions within class I viral fusion glycoproteins and essential for membrane fusion events during viral entry. The MPER in the human immunodeficiency virus type I (HIV-1) envelope protein (Env) interacts with the lipid bilayers through a cluster of tryptophan (Trp) residues and a C-terminal cholesterol-interacting motif. The inclusion of the MPER N-terminal sequence contributes to the membrane reactivity and anti-viral efficacy of the first two anti-HIV peptidyl fusion inhibitors T20 and T1249. As a type I transmembrane protein, Env also interacts with the cellular membranes during its biosynthesis and trafficking. Here we investigated the roles of MPER membrane-active sequences during both viral entry and assembly, specifically, their roles in the design of peptidyl fusion inhibitors and the biosynthesis of viral structural proteins. We found that elimination of the membrane-active elements in MPER peptides, namely, penta Trp→alanine (Ala) substitutions and the disruption of the C-terminal cholesterol-interacting motif through deletion inhibited the anti-viral effect against the pseudotyped HIV-1. Furthermore, as compared to C-terminal dimerization, N-terminal dimerization of MPER peptides and N-terminal extension with five helix-forming residues enhanced their anti-viral efficacy substantially. The secondary structure study revealed that the penta-Trp→Ala substitutions also increased the helical content in the MPER sequence, which prompted us to study the biological relevance of such mutations in pre-fusion Env. We observed that Ala mutations of Trp664, Trp668 and Trp670 in MPER moderately lowered the intracellular and intraviral contents of Env while significantly elevating the content of another viral structural protein, p55/Gag and its derivative p24/capsid. The data suggest a role of the gp41 MPER in the membrane-reactive events during both viral entry and budding, and provide insights into the future development of anti-viral therapeutics.",2015 Jul 31,"['Zhang, Si Min', 'Jejcic, Alenka', 'Tam, James P.', 'Vahlne, Anders']",PLoS One,,,True
d78b99436685b3f545dedc32f1166776b916abd6,PMC,"Development of an indirect ELISA, blocking ELISA, fluorescent microsphere immunoassay and fluorescent focus neutralization assay for serologic evaluation of exposure to North American strains of Porcine Epidemic Diarrhea Virus",http://dx.doi.org/10.1186/s12917-015-0500-z,PMC4522128,26232106,CC BY,"BACKGROUND: Recent, severe outbreaks of porcine epidemic diarrhea virus (PEDV) in Asia and North America highlight the need for well-validated diagnostic tests for the identification of PEDV infected animals and evaluation of their immune status to this virus. PEDV was first detected in the U.S. in May 2013 and spread rapidly across the country. Some serological assays for PEDV have been previously described, but few were readily available in the U.S. Several U.S. laboratories quickly developed indirect fluorescent antibody (IFA) assays for the detection of antibodies to PEDV in swine serum, indicating prior exposure. However, the IFA has several disadvantages, including low throughput and relatively subjective interpretation. Different serologic test formats have advantages and disadvantages, depending on the questions being asked, so a full repertoire of tests is useful. Therefore, the objective of this study was to develop and validate multiple improved serological assays for PEDV, including an indirect ELISA (iELISA); a highly specific monoclonal antibody-based blocking ELISA (bELISA); fluorescent microsphere immunoassays (FMIA) that can be multiplexed to monitor exposure to multiple antigens and pathogens simultaneously; and a fluorescent focus neutralization assay (FFN) to measure functional virus neutralizing antibodies. RESULTS: A recombinant North American nucleoprotein (NP) based iELISA was developed and validated along with a bELISA using newly developed PEDV-NP specific biotinylated monoclonal antibodies (mAbs) and an FMIA using magnetic beads coupled with expressed NA PEDV-NP. Receiver operating characteristic (ROC) analysis was performed using swine serum samples (iELISA n = 1486, bELISA n = 1186, FMIA n = 1420). The ROC analysis for the FMIA showed estimated sensitivity and specificity of 98.2 and 99.2 %, respectively. The iELISA and bELISA showed a sensitivity and specificity of 97.9 and 97.6 %; and 98.2 and 98.9 %, respectively. Inter-rater (kappa) agreement was calculated to be 0.941 between iELISA and IFA, 0.945 between bELISA and IFA and 0.932 between FMIA and IFA. Similar comparative kappa values were observed between the iELISA, bELISA and FMIA, which demonstrated a significant level of testing agreement among the three assays. No cross-reactivity with the closely related coronaviruses, transmissible gastroenteritis virus (TGEV) or porcine respiratory coronavirus (PRCV) was noted with these assays. All three assays detected seroconversion of naïve animals within 6–9 days post exposure. The FFN assay allows relative quantitation of functional neutralizing antibodies in serum, milk or colostrum samples. CONCLUSION: Well-validated iELISA, bELISA and FMIA assays for the detection of PEDV antibodies were developed and showed good correlation with IFA and each other. Each assay format has advantages that dictate how they will be used in the field. Newly developed mAbs to the PEDV-NP were used in the bELISA and for expediting FFN testing in the detection and quantitation of neutralizing antibodies. In addition, these PEDV mAbs are useful for immunohistochemistry, fluorescent antibody staining and other antigen-based tests. Measurement of neutralizing antibody responses using the FFN assay may provide a valuable tool for assessment of vaccine candidates or protective immunity.",2015 Aug 1,"['Okda, Faten', 'Liu, Xiaodong', 'Singrey, Aaron', 'Clement, Travis', 'Nelson, Julie', 'Christopher-Hennings, Jane', 'Nelson, Eric A.', 'Lawson, Steven']",BMC Vet Res,,,True
9efdb1c8ae8a36d1b0bd0dac741d0de23df2ac9e,PMC,Cytokine systems approach demonstrates differences in innate and pro-inflammatory host responses between genetically distinct MERS-CoV isolates,http://dx.doi.org/10.1186/1471-2164-15-1161,PMC4522970,25534508,CC BY,"BACKGROUND: The recent emergence of a novel coronavirus in the Middle East (designated MERS-CoV) is a reminder of the zoonotic and pathogenic potential of emerging coronaviruses in humans. Clinical features of Middle East respiratory syndrome (MERS) include atypical pneumonia and progressive respiratory failure that is highly reminiscent of severe acute respiratory syndrome (SARS) caused by SARS-CoV. The host response is a key component of highly pathogenic respiratory virus infection. Here, we computationally analyzed gene expression changes in a human airway epithelial cell line infected with two genetically distinct MERS-CoV strains obtained from human patients, MERS-CoV SA 1 and MERS-CoV Eng 1. RESULTS: Using topological techniques, including persistence homology and filtered clustering, we performed a comparative transcriptional analysis of human Calu-3 cell host responses to the different MERS-CoV strains, with MERS-CoV Eng 1 inducing early kinetic changes, between 3 and 12 hours post infection, compared to MERS-CoV SA 1. Robust transcriptional changes distinguished the two MERS-CoV strains predominantly at the late time points. Combining statistical analysis of infection and cytokine-stimulated Calu-3 transcriptomics, we identified differential innate responses, including up-regulation of extracellular remodeling genes following MERS-CoV Eng 1 infection and differential pro-inflammatory responses. CONCLUSIONS: Through our genomics-based approach, we found topological differences in the kinetics and magnitude of the host response to MERS-CoV SA 1 and MERS-CoV Eng 1, with differential expression of innate immune and pro-inflammatory responsive genes as a result of IFN, TNF and IL-1α signaling. Predicted activation for STAT3 mediating gene expression relevant for epithelial cell-to-cell adherens and junction signaling in MERS-CoV Eng 1 infection suggest that these transcriptional differences may be the result of amino acid differences in viral proteins known to modulate innate immunity during MERS-CoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1161) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Selinger, Christian', 'Tisoncik-Go, Jennifer', 'Menachery, Vineet D', 'Agnihothram, Sudhakar', 'Law, G Lynn', 'Chang, Jean', 'Kelly, Sara M', 'Sova, Pavel', 'Baric, Ralph S', 'Katze, Michael G']",BMC Genomics,,,False
a13166feda1f37450932faf548a882c927840ea1,PMC,Cytokine systems approach demonstrates differences in innate and pro-inflammatory host responses between genetically distinct MERS-CoV isolates,http://dx.doi.org/10.1186/1471-2164-15-1161,PMC4522970,25534508,CC BY,"BACKGROUND: The recent emergence of a novel coronavirus in the Middle East (designated MERS-CoV) is a reminder of the zoonotic and pathogenic potential of emerging coronaviruses in humans. Clinical features of Middle East respiratory syndrome (MERS) include atypical pneumonia and progressive respiratory failure that is highly reminiscent of severe acute respiratory syndrome (SARS) caused by SARS-CoV. The host response is a key component of highly pathogenic respiratory virus infection. Here, we computationally analyzed gene expression changes in a human airway epithelial cell line infected with two genetically distinct MERS-CoV strains obtained from human patients, MERS-CoV SA 1 and MERS-CoV Eng 1. RESULTS: Using topological techniques, including persistence homology and filtered clustering, we performed a comparative transcriptional analysis of human Calu-3 cell host responses to the different MERS-CoV strains, with MERS-CoV Eng 1 inducing early kinetic changes, between 3 and 12 hours post infection, compared to MERS-CoV SA 1. Robust transcriptional changes distinguished the two MERS-CoV strains predominantly at the late time points. Combining statistical analysis of infection and cytokine-stimulated Calu-3 transcriptomics, we identified differential innate responses, including up-regulation of extracellular remodeling genes following MERS-CoV Eng 1 infection and differential pro-inflammatory responses. CONCLUSIONS: Through our genomics-based approach, we found topological differences in the kinetics and magnitude of the host response to MERS-CoV SA 1 and MERS-CoV Eng 1, with differential expression of innate immune and pro-inflammatory responsive genes as a result of IFN, TNF and IL-1α signaling. Predicted activation for STAT3 mediating gene expression relevant for epithelial cell-to-cell adherens and junction signaling in MERS-CoV Eng 1 infection suggest that these transcriptional differences may be the result of amino acid differences in viral proteins known to modulate innate immunity during MERS-CoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1161) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Selinger, Christian', 'Tisoncik-Go, Jennifer', 'Menachery, Vineet D', 'Agnihothram, Sudhakar', 'Law, G Lynn', 'Chang, Jean', 'Kelly, Sara M', 'Sova, Pavel', 'Baric, Ralph S', 'Katze, Michael G']",BMC Genomics,,,False
49471df378964515ebc4e4f35f1248d84ac7d626,PMC,Cytokine systems approach demonstrates differences in innate and pro-inflammatory host responses between genetically distinct MERS-CoV isolates,http://dx.doi.org/10.1186/1471-2164-15-1161,PMC4522970,25534508,CC BY,"BACKGROUND: The recent emergence of a novel coronavirus in the Middle East (designated MERS-CoV) is a reminder of the zoonotic and pathogenic potential of emerging coronaviruses in humans. Clinical features of Middle East respiratory syndrome (MERS) include atypical pneumonia and progressive respiratory failure that is highly reminiscent of severe acute respiratory syndrome (SARS) caused by SARS-CoV. The host response is a key component of highly pathogenic respiratory virus infection. Here, we computationally analyzed gene expression changes in a human airway epithelial cell line infected with two genetically distinct MERS-CoV strains obtained from human patients, MERS-CoV SA 1 and MERS-CoV Eng 1. RESULTS: Using topological techniques, including persistence homology and filtered clustering, we performed a comparative transcriptional analysis of human Calu-3 cell host responses to the different MERS-CoV strains, with MERS-CoV Eng 1 inducing early kinetic changes, between 3 and 12 hours post infection, compared to MERS-CoV SA 1. Robust transcriptional changes distinguished the two MERS-CoV strains predominantly at the late time points. Combining statistical analysis of infection and cytokine-stimulated Calu-3 transcriptomics, we identified differential innate responses, including up-regulation of extracellular remodeling genes following MERS-CoV Eng 1 infection and differential pro-inflammatory responses. CONCLUSIONS: Through our genomics-based approach, we found topological differences in the kinetics and magnitude of the host response to MERS-CoV SA 1 and MERS-CoV Eng 1, with differential expression of innate immune and pro-inflammatory responsive genes as a result of IFN, TNF and IL-1α signaling. Predicted activation for STAT3 mediating gene expression relevant for epithelial cell-to-cell adherens and junction signaling in MERS-CoV Eng 1 infection suggest that these transcriptional differences may be the result of amino acid differences in viral proteins known to modulate innate immunity during MERS-CoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1161) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Selinger, Christian', 'Tisoncik-Go, Jennifer', 'Menachery, Vineet D', 'Agnihothram, Sudhakar', 'Law, G Lynn', 'Chang, Jean', 'Kelly, Sara M', 'Sova, Pavel', 'Baric, Ralph S', 'Katze, Michael G']",BMC Genomics,,,True
1db4560940a913194230a37755d10fa154b09d15,PMC,A comparative analysis of host responses to avian influenza infection in ducks and chickens highlights a role for the interferon-induced transmembrane proteins in viral resistance,http://dx.doi.org/10.1186/s12864-015-1778-8,PMC4523026,26238195,CC BY,"BACKGROUND: Chickens are susceptible to infection with a limited number of Influenza A viruses and are a potential source of a human influenza pandemic. In particular, H5 and H7 haemagglutinin subtypes can evolve from low to highly pathogenic strains in gallinaceous poultry. Ducks on the other hand are a natural reservoir for these viruses and are able to withstand most avian influenza strains. RESULTS: Transcriptomic sequencing of lung and ileum tissue samples from birds infected with high (H5N1) and low (H5N2) pathogenic influenza viruses has allowed us to compare the early host response to these infections in both these species. Chickens (but not ducks) lack the intracellular receptor for viral ssRNA, RIG-I and the gene for an important RIG-I binding protein, RNF135. These differences in gene content partly explain the differences in host responses to low pathogenic and highly pathogenic avian influenza virus in chicken and ducks. We reveal very different patterns of expression of members of the interferon-induced transmembrane protein (IFITM) gene family in ducks and chickens. In ducks, IFITM1, 2 and 3 are strongly up regulated in response to highly pathogenic avian influenza, where little response is seen in chickens. Clustering of gene expression profiles suggests IFITM1 and 2 have an anti-viral response and IFITM3 may restrict avian influenza virus through cell membrane fusion. We also show, through molecular phylogenetic analyses, that avian IFITM1 and IFITM3 genes have been subject to both episodic and pervasive positive selection at specific codons. In particular, avian IFITM1 showed evidence of positive selection in the duck lineage at sites known to restrict influenza virus infection. CONCLUSIONS: Taken together these results support a model where the IFITM123 protein family and RIG-I all play a crucial role in the tolerance of ducks to highly pathogenic and low pathogenic strains of avian influenza viruses when compared to the chicken. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1778-8) contains supplementary material, which is available to authorized users.",2015 Aug 4,"['Smith, Jacqueline', 'Smith, Nikki', 'Yu, Le', 'Paton, Ian R.', 'Gutowska, Maria Weronika', 'Forrest, Heather L.', 'Danner, Angela F.', 'Seiler, J. Patrick', 'Digard, Paul', 'Webster, Robert G.', 'Burt, David W.']",BMC Genomics,,,True
8d6ac4365bc4ab3f85ea3a5c287cddfaef482707,PMC,Comparison of Infectious Agents Susceptibility to Photocatalytic Effects of Nanosized Titanium and Zinc Oxides: A Practical Approach,http://dx.doi.org/10.1186/s11671-015-1023-z,PMC4523504,26239879,CC BY,"Nanotechnology contributes towards a more effective eradication of pathogens that have emerged in hospitals, veterinary clinics, and food processing plants and that are resistant to traditional drugs or disinfectants. Since new methods of pathogens eradication must be invented and implemented, nanotechnology seems to have become the response to that acute need. A remarkable achievement in this field of science was the creation of self-disinfecting surfaces that base on advanced oxidation processes (AOPs). Thus, the phenomenon of photocatalysis was practically applied. Among the AOPs that have been most studied in respect of their ability to eradicate viruses, prions, bacteria, yeasts, and molds, there are the processes of TiO(2)/UV and ZnO/UV. Titanium dioxide (TiO(2)) and zinc oxide (ZnO) act as photocatalysts, after they have been powdered to nanoparticles. Ultraviolet (UV) radiation is an agent that determines their excitation. Methods using photocatalytic properties of nanosized TiO(2) and ZnO prove to be highly efficient in inactivation of infectious agents. Therefore, they are being applied on a growing scale. AOP-based disinfection is regarded as a very promising tool that might help overcome problems in food hygiene and public health protection. The susceptibility of infectious agents to photocatalylic processes can be generally arranged in the following order: viruses > prions > Gram-negative bacteria > Gram-positive bacteria > yeasts > molds.",2015 Aug 4,"['Bogdan, Janusz', 'Zarzyńska, Joanna', 'Pławińska-Czarnak, Joanna']",Nanoscale Res Lett,,,True
d6ea3039fed0942c355cabc8a67f7226cd05fc8c,PMC,"IFN-β-inducing, unusual viral RNA species produced by paramyxovirus infection accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner",http://dx.doi.org/10.3389/fmicb.2015.00804,PMC4523817,26300870,CC BY,"The interferon (IFN) system is one of the most important defensive responses of mammals against viruses, and is rapidly evoked when the pathogen-associated molecular patterns (PAMPs) of viruses are sensed. Non-self, virus-derived RNA species have been identified as the PAMPs of RNA viruses. In the present study, we compared different types of IFN-β-inducing and -non-inducing viruses in the context of Sendai virus infection. We found that some types of unusual viral RNA species were produced by infections with IFN-β-inducing viruses and accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner. One of these structures was similar to the so-called antiviral stress granules (avSGs) formed by an infection with IFN-inducing viruses whose C proteins were knocked-out or mutated. Non-encapsidated, unusual viral RNA harboring the 5′-terminal region of the viral genome as well as RIG-I and typical SG markers accumulated in these granules. Another was a non-SG-like inclusion formed by an infection with the Cantell strain; a copyback-type DI genome, but not an authentic viral genome, specifically accumulated in the inclusion, whereas RIG-I and SG markers did not. The induction of IFN-β was closely associated with the production of these unusual RNAs as well as the formation of the cytoplasmic structures.",2015 Aug 4,"['Yoshida, Asuka', 'Kawabata, Ryoko', 'Honda, Tomoyuki', 'Tomonaga, Keizo', 'Sakaguchi, Takemasa', 'Irie, Takashi']",Front Microbiol,,,True
f00f183d0bce0091a02349ec1eab44a76dad9bc4,PMC,"Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold",http://dx.doi.org/10.3389/fmicb.2015.00755,PMC4523942,26300850,CC BY,"For the past 25 years, phage display technology has been an invaluable tool for studies of protein–protein interactions. However, the inherent biological, biochemical, and biophysical properties of filamentous bacteriophage, as well as the ease of its genetic manipulation, also make it an attractive platform outside the traditional phage display canon. This review will focus on the unique properties of the filamentous bacteriophage and highlight its diverse applications in current research. Particular emphases are placed on: (i) the advantages of the phage as a vaccine carrier, including its high immunogenicity, relative antigenic simplicity and ability to activate a range of immune responses, (ii) the phage’s potential as a prophylactic and therapeutic agent for infectious and chronic diseases, (iii) the regularity of the virion major coat protein lattice, which enables a variety of bioconjugation and surface chemistry applications, particularly in nanomaterials, and (iv) the phage’s large population sizes and fast generation times, which make it an excellent model system for directed protein evolution. Despite their ubiquity in the biosphere, metagenomics work is just beginning to explore the ecology of filamentous and non-filamentous phage, and their role in the evolution of bacterial populations. Thus, the filamentous phage represents a robust, inexpensive, and versatile microorganism whose bioengineering applications continue to expand in new directions, although its limitations in some spheres impose obstacles to its widespread adoption and use.",2015 Aug 4,"['Henry, Kevin A.', 'Arbabi-Ghahroudi, Mehdi', 'Scott, Jamie K.']",Front Microbiol,,,True
b62ce73d8d2c9e794c96ce0be7d52ed55b87fa52,PMC,Application of recombinant severe fever with thrombocytopenia syndrome virus nucleocapsid protein for the detection of SFTSV-specific human IgG and IgM antibodies by indirect ELISA,http://dx.doi.org/10.1186/s12985-015-0350-0,PMC4524020,26239826,CC BY,"BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease that was first reported in China in 2011. It is caused by SFTS virus (SFTSV) which is a member of the Phlebovirus genus in the Bunyaviridae family. SFTSV has been classified as a BSL3 pathogen. There is a need to develop safe and affordable serodiagnostic methods for proper clinical management of infected patients. METHODS: The full length nucleocapsid (N) gene of SFTSV Yamaguchi strain was amplified by RT-PCR and cloned to an expression vector pQE30. The recombinant (r) SFTSV-N protein was expressed by using Escherichia coli (E. coli) expression system and purified under native conditions. rSFTSV-N protein based indirect IgG and IgM enzyme linked immunosorbent assay (ELISA) systems were established to detect specific human IgG and IgM antibodies, respectively. One hundred fifteen serum samples from clinically suspected-SFTS patients were used to evaluate the newly established systems and the results were compared with the total antibody detecting sandwich ELISA system. RESULTS: The native form of recombinant (r) SFTSV-N protein was expressed and purified. Application of the rSFTSV-N protein based indirect IgG ELISA to the 115 serum samples showed results that perfectly matched those of the total antibody sandwich ELISA with a sensitivity and specificity of 100 %. The rSFTSV-N protein based indirect IgM ELISA missed 8 positive samples that were detected by the total antibody sandwich ELISA. The sensitivity and specificity of rSFTSV-N-IgM capture ELISA were 90.59 and 100 %, respectively. CONCLUSIONS: The rSFTSV-N protein is highly immunoreactive and a good target for use as an assay antigen in laboratory diagnosis. Its preparation is simpler in comparison with that used for the total antibody sandwich system. Our rSFTSV-N protein-based IgG and IgM ELISA systems have the advantage of distinguishing two types of antibodies and require small volume of serum sample only. They are safe to use for diagnosis of SFTS virus infection and especially fit in large-scale epidemiological investigations.",2015 Aug 4,"['Yu, Fuxun', 'Du, Yanhua', 'Huang, Xueyong', 'Ma, Hong', 'Xu, Bianli', 'Adungo, Ferdinard', 'Hayasaka, Daisuke', 'Buerano, Corazon C.', 'Morita, Kouichi']",Virol J,,,True
f831181b0266734c1f277c223956e61e0a42b350,PMC,Characterization of Ribosomal Frameshifting in Theiler's Murine Encephalomyelitis Virus,http://dx.doi.org/10.1128/JVI.01043-15,PMC4524249,26063423,CC BY,"Theiler's murine encephalomyelitis virus (TMEV) is a member of the genus Cardiovirus in the Picornaviridae, a family of positive-sense single-stranded RNA viruses. Previously, we demonstrated that in the related cardiovirus, Encephalomyocarditis virus, a programmed −1 ribosomal frameshift (−1 PRF) occurs at a conserved G_GUU_UUU sequence within the 2B-encoding region of the polyprotein open reading frame (ORF). Here we show that −1 PRF occurs at a similar site during translation of the TMEV genome. In addition, we demonstrate that a predicted 3′ RNA stem-loop structure at a noncanonical spacing downstream of the shift site is required for efficient frameshifting in TMEV and that frameshifting also requires virus infection. Mutating the G_GUU_UUU shift site to inhibit frameshifting results in an attenuated virus with reduced growth kinetics and a small-plaque phenotype. Frameshifting in the virus context was found to be extremely efficient at 74 to 82%, which, to our knowledge, is the highest frameshifting efficiency recorded to date for any virus. We propose that highly efficient −1 PRF in TMEV provides a mechanism to escape the confines of equimolar expression normally inherent in the single-polyprotein expression strategy of picornaviruses. IMPORTANCE Many viruses utilize programmed −1 ribosomal frameshifting (−1 PRF) to produce different protein products at a defined ratio, or to translate overlapping ORFs to increase coding capacity. With few exceptions, −1 PRF occurs on specific “slippery” heptanucleotide sequences and is stimulated by RNA structure beginning 5 to 9 nucleotides (nt) downstream of the slippery site. Here we describe an unusual case of −1 PRF in Theiler's murine encephalomyelitis virus (TMEV) that is extraordinarily efficient (74 to 82% of ribosomes shift into the alternative reading frame) and, in stark contrast to other examples of −1 PRF, is dependent upon a stem-loop structure beginning 14 nt downstream of the slippery site. Furthermore, in TMEV-based reporter constructs in transfected cells, efficient frameshifting is critically dependent upon virus infection. We suggest that TMEV evolved frameshifting as a novel mechanism for removing ribosomes from the message (a “ribosome sink”) to downregulate synthesis of the 3′-encoded replication proteins.",2015 Jun 10,"['Finch, Leanne K.', 'Ling, Roger', 'Napthine, Sawsan', 'Olspert, Allan', 'Michiels, Thomas', 'Lardinois, Cécile', 'Bell, Susanne', 'Loughran, Gary', 'Brierley, Ian', 'Firth, Andrew E.']",J Virol,,,False
975a7b5f0f9a7f9a03195cb5cd1a633ecd4e36f8,PMC,Characterization of Ribosomal Frameshifting in Theiler's Murine Encephalomyelitis Virus,http://dx.doi.org/10.1128/JVI.01043-15,PMC4524249,26063423,CC BY,"Theiler's murine encephalomyelitis virus (TMEV) is a member of the genus Cardiovirus in the Picornaviridae, a family of positive-sense single-stranded RNA viruses. Previously, we demonstrated that in the related cardiovirus, Encephalomyocarditis virus, a programmed −1 ribosomal frameshift (−1 PRF) occurs at a conserved G_GUU_UUU sequence within the 2B-encoding region of the polyprotein open reading frame (ORF). Here we show that −1 PRF occurs at a similar site during translation of the TMEV genome. In addition, we demonstrate that a predicted 3′ RNA stem-loop structure at a noncanonical spacing downstream of the shift site is required for efficient frameshifting in TMEV and that frameshifting also requires virus infection. Mutating the G_GUU_UUU shift site to inhibit frameshifting results in an attenuated virus with reduced growth kinetics and a small-plaque phenotype. Frameshifting in the virus context was found to be extremely efficient at 74 to 82%, which, to our knowledge, is the highest frameshifting efficiency recorded to date for any virus. We propose that highly efficient −1 PRF in TMEV provides a mechanism to escape the confines of equimolar expression normally inherent in the single-polyprotein expression strategy of picornaviruses. IMPORTANCE Many viruses utilize programmed −1 ribosomal frameshifting (−1 PRF) to produce different protein products at a defined ratio, or to translate overlapping ORFs to increase coding capacity. With few exceptions, −1 PRF occurs on specific “slippery” heptanucleotide sequences and is stimulated by RNA structure beginning 5 to 9 nucleotides (nt) downstream of the slippery site. Here we describe an unusual case of −1 PRF in Theiler's murine encephalomyelitis virus (TMEV) that is extraordinarily efficient (74 to 82% of ribosomes shift into the alternative reading frame) and, in stark contrast to other examples of −1 PRF, is dependent upon a stem-loop structure beginning 14 nt downstream of the slippery site. Furthermore, in TMEV-based reporter constructs in transfected cells, efficient frameshifting is critically dependent upon virus infection. We suggest that TMEV evolved frameshifting as a novel mechanism for removing ribosomes from the message (a “ribosome sink”) to downregulate synthesis of the 3′-encoded replication proteins.",2015 Jun 10,"['Finch, Leanne K.', 'Ling, Roger', 'Napthine, Sawsan', 'Olspert, Allan', 'Michiels, Thomas', 'Lardinois, Cécile', 'Bell, Susanne', 'Loughran, Gary', 'Brierley, Ian', 'Firth, Andrew E.']",J Virol,,,True
d38f4068c4bf5d99a9f4fc20b1914a3332a42ead,PMC,Phylogenetic analysis of avian infectious bronchitis virus S1 glycoprotein regions reveals emergence of a new genotype in Moroccan broiler chicken flocks,http://dx.doi.org/10.1186/s12985-015-0347-8,PMC4524495,26239707,CC BY,"BACKGROUND: Infectious bronchitis virus (IBV), a major pathogen of commercial poultry flocks, circulates in the form of several serotypes/genotypes. Only a few amino-acid changes in the S1 subunit of wild-type IBVS proteins may result in mutants unaffected by current vaccines. METHODS: Partial S1 gene sequences of 3 IBV isolates of the Moroccan Italy 02 genotype from vaccinated and unvaccinated broiler chicken flocks, located in southern and central regions of Morocco, were amplified by RT-PCR, sequenced, and aligned for phylogenetic and amino-acid similarity analyses. RESULTS: The three isolates were found genetically highly distant from known avian IBV based on partial sequences of their S1 genes: gammaCoV/chicken/Morocco/I01/2011(IBV/Morocco/01), gammaCoV/chicken/Morocco/I30/2010 (IBV/Morocco/30), and gammaCoV/chicken/Morocco/I38/2013 (IBV/Morocco/38), nucleotide sequence identities reached 89.5 % to 90.9 % among the three isolates. The deduced protein sequence identities ranged from 29.7 % (between IBV/Morocco/38 and Egypt SCU-14/2013-1) to 78.2 % (between IBV/Morocco/01 and Spain/05/866). Amino acid sequence comparison and phylogenetic analysis indicated the emergence of a new Moroccan genotype, clustering with regionally related isolates from Spain (Spain/05/866) and belonging to a new sub-genotype. CONCLUSION: Our sequencing results demonstrate a co-circulation of wild-type infectious bronchitis viruses in broiler chickens. These results justify permanent monitoring of circulating strains in order to rationally modify vaccination strategies to make them appropriate to the evolving field situation.",2015 Aug 4,"['Fellahi, Siham', 'EL Harrak, Mehdi', 'Ducatez, Mariette', 'Loutfi, Chafiqa', 'Koraichi, Saad Ibn Souda', 'Kuhn, Jens H.', 'Khayi, Slimane', 'EL Houadfi, Mohammed', 'Ennaji, My Mustapha']",Virol J,,,True
96f74d611693ebad68d8cd10862e9a972bd3bdc5,PMC,Evaluation of candidate vaccine approaches for MERS-CoV,http://dx.doi.org/10.1038/ncomms8712,PMC4525294,26218507,CC BY,"The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.",2015 Jul 28,"['Wang, Lingshu', 'Shi, Wei', 'Joyce, M. Gordon', 'Modjarrad, Kayvon', 'Zhang, Yi', 'Leung, Kwanyee', 'Lees, Christopher R.', 'Zhou, Tongqing', 'Yassine, Hadi M.', 'Kanekiyo, Masaru', 'Yang, Zhi-yong', 'Chen, Xuejun', 'Becker, Michelle M.', 'Freeman, Megan', 'Vogel, Leatrice', 'Johnson, Joshua C.', 'Olinger, Gene', 'Todd, John P.', 'Bagci, Ulas', 'Solomon, Jeffrey', 'Mollura, Daniel J.', 'Hensley, Lisa', 'Jahrling, Peter', 'Denison, Mark R.', 'Rao, Srinivas S.', 'Subbarao, Kanta', 'Kwong, Peter D.', 'Mascola, John R.', 'Kong, Wing-Pui', 'Graham, Barney S.']",Nat Commun,,,True
83a9e757fc42183eef4f36f50cf84044f7b780fb,PMC,Evaluation of candidate vaccine approaches for MERS-CoV,http://dx.doi.org/10.1038/ncomms8712,PMC4525294,26218507,CC BY,"The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.",2015 Jul 28,"['Wang, Lingshu', 'Shi, Wei', 'Joyce, M. Gordon', 'Modjarrad, Kayvon', 'Zhang, Yi', 'Leung, Kwanyee', 'Lees, Christopher R.', 'Zhou, Tongqing', 'Yassine, Hadi M.', 'Kanekiyo, Masaru', 'Yang, Zhi-yong', 'Chen, Xuejun', 'Becker, Michelle M.', 'Freeman, Megan', 'Vogel, Leatrice', 'Johnson, Joshua C.', 'Olinger, Gene', 'Todd, John P.', 'Bagci, Ulas', 'Solomon, Jeffrey', 'Mollura, Daniel J.', 'Hensley, Lisa', 'Jahrling, Peter', 'Denison, Mark R.', 'Rao, Srinivas S.', 'Subbarao, Kanta', 'Kwong, Peter D.', 'Mascola, John R.', 'Kong, Wing-Pui', 'Graham, Barney S.']",Nat Commun,,,True
bae5b0168a883973407af7229c5f3b59020cdfa4,PMC,Aeromonas salmonicida Infection Only Moderately Regulates Expression of Factors Contributing to Toll-Like Receptor Signaling but Massively Activates the Cellular and Humoral Branches of Innate Immunity in Rainbow Trout (Oncorhynchus mykiss),http://dx.doi.org/10.1155/2015/901015,PMC4525466,26266270,CC BY,"Toll-like receptors (TLRs) are known to detect a defined spectrum of microbial structures. However, the knowledge about the specificity of teleost Tlr factors for distinct pathogens is limited so far. We measured baseline expression profiles of 18 tlr genes and associated signaling factors in four immune-relevant tissues of rainbow trout Oncorhynchus mykiss. Intraperitoneal injection of a lethal dose of Aeromonas salmonicida subsp. salmonicida induced highly increased levels of cytokine mRNAs during a 72-hour postinfection (hpi) period. In contrast, only the fish-specific tlr22a2 and the downstream factor irak1 featured clearly increased transcript levels, while the mRNA concentrations of many other tlr genes decreased. Flow cytometry quantified cell trafficking after infection indicating a dramatic influx of myeloid cells into the peritoneum and a belated low level immigration of lymphoid cells. T and B lymphocytes were differentiated with RT-qPCR revealing that B lymphocytes emigrated from and T lymphocytes immigrated into head kidney. In conclusion, no specific TLR can be singled out as a dominant receptor for A. salmonicida. The recruitment of cellular factors of innate immunity rather than induced expression of pathogen receptors is hence of key importance for mounting a first immune defense against invading A. salmonicida.",2015 Jul 22,"['Brietzke, Andreas', 'Korytář, Tomáš', 'Jaros, Joanna', 'Köllner, Bernd', 'Goldammer, Tom', 'Seyfert, Hans-Martin', 'Rebl, Alexander']",J Immunol Res,,,True
506d16aa50b90556febfdfdcdfed1a017df40ce8,PMC,MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet,http://dx.doi.org/10.1186/s12933-015-0252-x,PMC4526192,26242235,CC BY,"BACKGROUND: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2−/− hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. METHODS: MuRF2−/− mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1-regulated mRNA expression. RESULTS: MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2−/− hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2−/− hearts had significantly increased PPARα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2’s regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However, increasing MuRF2:PPARγ1 (>5:1) beyond physiological levels drove poly-ubiquitin-mediated degradation of PPARγ1 in vitro, indicating large MuRF2 increases may lead to PPAR degradation if found in other disease states. CONCLUSIONS: Mutations in MuRF2 have been described to contribute to the severity of familial hypertrophic cardiomyopathy. The present study suggests that the lack of MuRF2, as found in these patients, can result in an exaggerated diabetic cardiomyopathy. These studies also identify MuRF2 as the first ubiquitin ligase to regulate cardiac PPARα and PPARγ1 activities in vivo via post-translational modification without degradation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-015-0252-x) contains supplementary material, which is available to authorized users.",2015 Aug 5,"['He, Jun', 'Quintana, Megan T', 'Sullivan, Jenyth', 'L Parry, Traci', 'J Grevengoed, Trisha', 'Schisler, Jonathan C', 'Hill, Joseph A', 'Yates, Cecelia C', 'Mapanga, Rudo F', 'Essop, M Faadiel', 'Stansfield, William E', 'Bain, James R', 'Newgard, Christopher B', 'Muehlbauer, Michael J', 'Han, Yipin', 'Clarke, Brian A', 'Willis, Monte S']",Cardiovasc Diabetol,,,False
216552de85d6c86d4c92c8d66673332c6471bc2e,PMC,MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet,http://dx.doi.org/10.1186/s12933-015-0252-x,PMC4526192,26242235,CC BY,"BACKGROUND: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2−/− hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. METHODS: MuRF2−/− mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1-regulated mRNA expression. RESULTS: MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2−/− hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2−/− hearts had significantly increased PPARα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2’s regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However, increasing MuRF2:PPARγ1 (>5:1) beyond physiological levels drove poly-ubiquitin-mediated degradation of PPARγ1 in vitro, indicating large MuRF2 increases may lead to PPAR degradation if found in other disease states. CONCLUSIONS: Mutations in MuRF2 have been described to contribute to the severity of familial hypertrophic cardiomyopathy. The present study suggests that the lack of MuRF2, as found in these patients, can result in an exaggerated diabetic cardiomyopathy. These studies also identify MuRF2 as the first ubiquitin ligase to regulate cardiac PPARα and PPARγ1 activities in vivo via post-translational modification without degradation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-015-0252-x) contains supplementary material, which is available to authorized users.",2015 Aug 5,"['He, Jun', 'Quintana, Megan T', 'Sullivan, Jenyth', 'L Parry, Traci', 'J Grevengoed, Trisha', 'Schisler, Jonathan C', 'Hill, Joseph A', 'Yates, Cecelia C', 'Mapanga, Rudo F', 'Essop, M Faadiel', 'Stansfield, William E', 'Bain, James R', 'Newgard, Christopher B', 'Muehlbauer, Michael J', 'Han, Yipin', 'Clarke, Brian A', 'Willis, Monte S']",Cardiovasc Diabetol,,,False
31ee178148fc34c988d2deb5637c98ef944c7a7a,PMC,MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet,http://dx.doi.org/10.1186/s12933-015-0252-x,PMC4526192,26242235,CC BY,"BACKGROUND: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2−/− hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. METHODS: MuRF2−/− mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1-regulated mRNA expression. RESULTS: MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2−/− hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2−/− hearts had significantly increased PPARα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2’s regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However, increasing MuRF2:PPARγ1 (>5:1) beyond physiological levels drove poly-ubiquitin-mediated degradation of PPARγ1 in vitro, indicating large MuRF2 increases may lead to PPAR degradation if found in other disease states. CONCLUSIONS: Mutations in MuRF2 have been described to contribute to the severity of familial hypertrophic cardiomyopathy. The present study suggests that the lack of MuRF2, as found in these patients, can result in an exaggerated diabetic cardiomyopathy. These studies also identify MuRF2 as the first ubiquitin ligase to regulate cardiac PPARα and PPARγ1 activities in vivo via post-translational modification without degradation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-015-0252-x) contains supplementary material, which is available to authorized users.",2015 Aug 5,"['He, Jun', 'Quintana, Megan T', 'Sullivan, Jenyth', 'L Parry, Traci', 'J Grevengoed, Trisha', 'Schisler, Jonathan C', 'Hill, Joseph A', 'Yates, Cecelia C', 'Mapanga, Rudo F', 'Essop, M Faadiel', 'Stansfield, William E', 'Bain, James R', 'Newgard, Christopher B', 'Muehlbauer, Michael J', 'Han, Yipin', 'Clarke, Brian A', 'Willis, Monte S']",Cardiovasc Diabetol,,,False
fd33aae6b2e5c09fa0ea3afade3bc2cc836946cf,PMC,MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet,http://dx.doi.org/10.1186/s12933-015-0252-x,PMC4526192,26242235,CC BY,"BACKGROUND: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2−/− hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. METHODS: MuRF2−/− mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1-regulated mRNA expression. RESULTS: MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2−/− hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2−/− hearts had significantly increased PPARα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2’s regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However, increasing MuRF2:PPARγ1 (>5:1) beyond physiological levels drove poly-ubiquitin-mediated degradation of PPARγ1 in vitro, indicating large MuRF2 increases may lead to PPAR degradation if found in other disease states. CONCLUSIONS: Mutations in MuRF2 have been described to contribute to the severity of familial hypertrophic cardiomyopathy. The present study suggests that the lack of MuRF2, as found in these patients, can result in an exaggerated diabetic cardiomyopathy. These studies also identify MuRF2 as the first ubiquitin ligase to regulate cardiac PPARα and PPARγ1 activities in vivo via post-translational modification without degradation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-015-0252-x) contains supplementary material, which is available to authorized users.",2015 Aug 5,"['He, Jun', 'Quintana, Megan T', 'Sullivan, Jenyth', 'L Parry, Traci', 'J Grevengoed, Trisha', 'Schisler, Jonathan C', 'Hill, Joseph A', 'Yates, Cecelia C', 'Mapanga, Rudo F', 'Essop, M Faadiel', 'Stansfield, William E', 'Bain, James R', 'Newgard, Christopher B', 'Muehlbauer, Michael J', 'Han, Yipin', 'Clarke, Brian A', 'Willis, Monte S']",Cardiovasc Diabetol,,,False
a00518a38dd5b19f2774ea3c2b530fd9595113e0,PMC,MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet,http://dx.doi.org/10.1186/s12933-015-0252-x,PMC4526192,26242235,CC BY,"BACKGROUND: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2−/− hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. METHODS: MuRF2−/− mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1-regulated mRNA expression. RESULTS: MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2−/− hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2−/− hearts had significantly increased PPARα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2’s regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However, increasing MuRF2:PPARγ1 (>5:1) beyond physiological levels drove poly-ubiquitin-mediated degradation of PPARγ1 in vitro, indicating large MuRF2 increases may lead to PPAR degradation if found in other disease states. CONCLUSIONS: Mutations in MuRF2 have been described to contribute to the severity of familial hypertrophic cardiomyopathy. The present study suggests that the lack of MuRF2, as found in these patients, can result in an exaggerated diabetic cardiomyopathy. These studies also identify MuRF2 as the first ubiquitin ligase to regulate cardiac PPARα and PPARγ1 activities in vivo via post-translational modification without degradation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-015-0252-x) contains supplementary material, which is available to authorized users.",2015 Aug 5,"['He, Jun', 'Quintana, Megan T', 'Sullivan, Jenyth', 'L Parry, Traci', 'J Grevengoed, Trisha', 'Schisler, Jonathan C', 'Hill, Joseph A', 'Yates, Cecelia C', 'Mapanga, Rudo F', 'Essop, M Faadiel', 'Stansfield, William E', 'Bain, James R', 'Newgard, Christopher B', 'Muehlbauer, Michael J', 'Han, Yipin', 'Clarke, Brian A', 'Willis, Monte S']",Cardiovasc Diabetol,,,False
f29df5233e688dddd0286374e0993e43459fe04b,PMC,MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet,http://dx.doi.org/10.1186/s12933-015-0252-x,PMC4526192,26242235,CC BY,"BACKGROUND: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2−/− hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. METHODS: MuRF2−/− mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1-regulated mRNA expression. RESULTS: MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2−/− hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2−/− hearts had significantly increased PPARα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2’s regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However, increasing MuRF2:PPARγ1 (>5:1) beyond physiological levels drove poly-ubiquitin-mediated degradation of PPARγ1 in vitro, indicating large MuRF2 increases may lead to PPAR degradation if found in other disease states. CONCLUSIONS: Mutations in MuRF2 have been described to contribute to the severity of familial hypertrophic cardiomyopathy. The present study suggests that the lack of MuRF2, as found in these patients, can result in an exaggerated diabetic cardiomyopathy. These studies also identify MuRF2 as the first ubiquitin ligase to regulate cardiac PPARα and PPARγ1 activities in vivo via post-translational modification without degradation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-015-0252-x) contains supplementary material, which is available to authorized users.",2015 Aug 5,"['He, Jun', 'Quintana, Megan T', 'Sullivan, Jenyth', 'L Parry, Traci', 'J Grevengoed, Trisha', 'Schisler, Jonathan C', 'Hill, Joseph A', 'Yates, Cecelia C', 'Mapanga, Rudo F', 'Essop, M Faadiel', 'Stansfield, William E', 'Bain, James R', 'Newgard, Christopher B', 'Muehlbauer, Michael J', 'Han, Yipin', 'Clarke, Brian A', 'Willis, Monte S']",Cardiovasc Diabetol,,,True
74b1c6107f2da5209abaa2521b5a93d885e74cf5,PMC,Epidemic Wave Dynamics Attributable to Urban Community Structure: A Theoretical Characterization of Disease Transmission in a Large Network,http://dx.doi.org/10.2196/jmir.3720,PMC4526984,26156032,CC BY,"BACKGROUND: Multiple waves of transmission during infectious disease epidemics represent a major public health challenge, but the ecological and behavioral drivers of epidemic resurgence are poorly understood. In theory, community structure—aggregation into highly intraconnected and loosely interconnected social groups—within human populations may lead to punctuated outbreaks as diseases progress from one community to the next. However, this explanation has been largely overlooked in favor of temporal shifts in environmental conditions and human behavior and because of the difficulties associated with estimating large-scale contact patterns. OBJECTIVE: The aim was to characterize naturally arising patterns of human contact that are capable of producing simulated epidemics with multiple wave structures. METHODS: We used an extensive dataset of proximal physical contacts between users of a public Wi-Fi Internet system to evaluate the epidemiological implications of an empirical urban contact network. We characterized the modularity (community structure) of the network and then estimated epidemic dynamics under a percolation-based model of infectious disease spread on the network. We classified simulated epidemics as multiwave using a novel metric and we identified network structures that were critical to the network’s ability to produce multiwave epidemics. RESULTS: We identified robust community structure in a large, empirical urban contact network from which multiwave epidemics may emerge naturally. This pattern was fueled by a special kind of insularity in which locally popular individuals were not the ones forging contacts with more distant social groups. CONCLUSIONS: Our results suggest that ordinary contact patterns can produce multiwave epidemics at the scale of a single urban area without the temporal shifts that are usually assumed to be responsible. Understanding the role of community structure in epidemic dynamics allows officials to anticipate epidemic resurgence without having to forecast future changes in hosts, pathogens, or the environment.",2015 Jul 8,"['Hoen, Anne G', 'Hladish, Thomas J', 'Eggo, Rosalind M', 'Lenczner, Michael', 'Brownstein, John S', 'Meyers, Lauren Ancel']",J Med Internet Res,,,False
8bc561d5b5716c07c70a69f724f0cc96dcb2e40f,PMC,Epidemic Wave Dynamics Attributable to Urban Community Structure: A Theoretical Characterization of Disease Transmission in a Large Network,http://dx.doi.org/10.2196/jmir.3720,PMC4526984,26156032,CC BY,"BACKGROUND: Multiple waves of transmission during infectious disease epidemics represent a major public health challenge, but the ecological and behavioral drivers of epidemic resurgence are poorly understood. In theory, community structure—aggregation into highly intraconnected and loosely interconnected social groups—within human populations may lead to punctuated outbreaks as diseases progress from one community to the next. However, this explanation has been largely overlooked in favor of temporal shifts in environmental conditions and human behavior and because of the difficulties associated with estimating large-scale contact patterns. OBJECTIVE: The aim was to characterize naturally arising patterns of human contact that are capable of producing simulated epidemics with multiple wave structures. METHODS: We used an extensive dataset of proximal physical contacts between users of a public Wi-Fi Internet system to evaluate the epidemiological implications of an empirical urban contact network. We characterized the modularity (community structure) of the network and then estimated epidemic dynamics under a percolation-based model of infectious disease spread on the network. We classified simulated epidemics as multiwave using a novel metric and we identified network structures that were critical to the network’s ability to produce multiwave epidemics. RESULTS: We identified robust community structure in a large, empirical urban contact network from which multiwave epidemics may emerge naturally. This pattern was fueled by a special kind of insularity in which locally popular individuals were not the ones forging contacts with more distant social groups. CONCLUSIONS: Our results suggest that ordinary contact patterns can produce multiwave epidemics at the scale of a single urban area without the temporal shifts that are usually assumed to be responsible. Understanding the role of community structure in epidemic dynamics allows officials to anticipate epidemic resurgence without having to forecast future changes in hosts, pathogens, or the environment.",2015 Jul 8,"['Hoen, Anne G', 'Hladish, Thomas J', 'Eggo, Rosalind M', 'Lenczner, Michael', 'Brownstein, John S', 'Meyers, Lauren Ancel']",J Med Internet Res,,,False
38486671848611786384f2cc0a49066c5fca595f,PMC,Interdisciplinarity and Infectious Diseases: An Ebola Case Study,http://dx.doi.org/10.1371/journal.ppat.1004992,PMC4527690,26247831,CC BY,,2015 Aug 6,"['Ezenwa, Vanessa O.', 'Prieur-Richard, Anne-Helene', 'Roche, Benjamin', 'Bailly, Xavier', 'Becquart, Pierre', 'García-Peña, Gabriel E.', 'Hosseini, Parviez R.', 'Keesing, Felicia', 'Rizzoli, Annapaola', 'Suzán, Gerardo', 'Vignuzzi, Marco', 'Vittecoq, Marion', 'Mills, James N.', 'Guégan, Jean-François']",PLoS Pathog,,,True
078b6935fa30cd20a00da6c6182e85b41ab4d9c5,PMC,Damage/Danger Associated Molecular Patterns (DAMPs) Modulate Chlamydia pecorum and C. trachomatis Serovar E Inclusion Development In Vitro,http://dx.doi.org/10.1371/journal.pone.0134943,PMC4527707,26248286,CC0,"Persistence, more recently termed the chlamydial stress response, is a viable but non-infectious state constituting a divergence from the characteristic chlamydial biphasic developmental cycle. Damage/danger associated molecular patterns (DAMPs) are normal intracellular components or metabolites that, when released from cells, signal cellular damage/lysis. Purine metabolite DAMPs, including extracellular ATP and adenosine, inhibit chlamydial development in a species-specific manner. Viral co-infection has been shown to reversibly abrogate Chlamydia inclusion development, suggesting persistence/chlamydial stress. Because viral infection can cause host cell DAMP release, we hypothesized DAMPs may influence chlamydial development. Therefore, we examined the effect of extracellular ATP, adenosine, and cyclic AMP exposure, at 0 and 14 hours post infection, on C. pecorum and C. trachomatis serovar E development. In the absence of de novo host protein synthesis, exposure to DAMPs immediately post or at 14 hours post infection reduced inclusion size; however, the effect was less robust upon 14 hours post infection exposure. Additionally, upon exposure to DAMPs immediately post infection, bacteria per inclusion and subsequent infectivity were reduced in both Chlamydia species. These effects were reversible, and C. pecorum exhibited more pronounced recovery from DAMP exposure. Aberrant bodies, typical in virus-induced chlamydial persistence, were absent upon DAMP exposure. In the presence of de novo host protein synthesis, exposure to DAMPs immediately post infection reduced inclusion size, but only variably modulated chlamydial infectivity. Because chlamydial infection and other infections may increase local DAMP concentrations, DAMPs may influence Chlamydia infection in vivo, particularly in the context of poly-microbial infections.",2015 Aug 6,"['Leonard, Cory Ann', 'Schoborg, Robert V.', 'Borel, Nicole']",PLoS One,,,True
d31b2db65b2e8d40eee096d5e67185099c10c4d2,PMC,Basal Autophagy Is Required for Herpes simplex Virus-2 Infection,http://dx.doi.org/10.1038/srep12985,PMC4528227,26248741,CC BY,"Autophagy is a conserved catabolic process of the cell, which plays an important role in regulating plethora of infections. The role of autophagy in Herpes simplex virus-2 (HSV-2) infection is unknown. Here, we found that HSV-2 does not allow induction of an autophagic response to infection, but maintains basal autophagy levels mostly unchanged during productive infection. Thus, we investigated the importance of basal autophagy for HSV-2 infection, using pharmacological autophagy suppression or cells genetically deficient in an autophagy-essential gene (ATG5). Interference with basal autophagy flux in cells significantly reduced viral replication and diminished the infection. These results indicate that basal autophagy plays an indispensable role required for a productive infection. Importantly, this study draws a sharp distinction between induced and basal autophagy, where the former acts as a viral clearance mechanism abrogating infection, while the latter supports infection.",2015 Aug 7,"['Yakoub, Abraam M.', 'Shukla, Deepak']",Sci Rep,,,True
474dc8b54f9110f60b129220549c532355fe10b2,PMC,"The Dipeptidyl Peptidase Family, Prolyl Oligopeptidase, and Prolyl Carboxypeptidase in the Immune System and Inflammatory Disease, Including Atherosclerosis",http://dx.doi.org/10.3389/fimmu.2015.00387,PMC4528296,26300881,CC BY,"Research from over the past 20 years has implicated dipeptidyl peptidase (DPP) IV and its family members in many processes and different pathologies of the immune system. Most research has been focused on either DPPIV or just a few of its family members. It is, however, essential to consider the entire DPP family when discussing any one of its members. There is a substantial overlap between family members in their substrate specificity, inhibitors, and functions. In this review, we provide a comprehensive discussion on the role of prolyl-specific peptidases DPPIV, FAP, DPP8, DPP9, dipeptidyl peptidase II, prolyl carboxypeptidase, and prolyl oligopeptidase in the immune system and its diseases. We highlight possible therapeutic targets for the prevention and treatment of atherosclerosis, a condition that lies at the frontier between inflammation and cardiovascular disease.",2015 Aug 7,"['Waumans, Yannick', 'Baerts, Lesley', 'Kehoe, Kaat', 'Lambeir, Anne-Marie', 'De Meester, Ingrid']",Front Immunol,,,True
96a20376534b0725c4cbd316e15d003d2183436b,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,True
eb784c2597d60b7a250f358bce5192afbc5ee52c,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
51f014265335a090e751bab6d11681af1c9eda3a,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
9f1d8594e18a9810c76e8df9d0e45eb96107988f,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
a3b4eba0e843b0214bd7c43535c87dfb7406e16a,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
fa58494e76abe64e7e107171ace85c5cd6ed6980,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
9ca2858fbcf3604a833c3334703f62b92e524b6c,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
fd5e2e2f8024eecb3611e4ca20d53aca0b0a9f32,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
1621c4ee9abc3983f8d2b8bd83270cc10ee04189,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
4af692eecd2b11d44d07ebd686017780c90d06bf,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
0e9a9468b6f5cca7ff28d5df02da29b65b7ac07b,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
1df9d3600307acda32a25a59dfe68d06222ba6f3,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
51f88d6a65a66742a19ec634400f8315fda5811e,PMC,Highly conserved regions in Ebola virus RNA dependent RNA polymerase may be act as a universal novel peptide vaccine target: a computational approach,http://dx.doi.org/10.1186/s40203-015-0011-4,PMC4529428,26820892,CC BY,"PURPOSE: Ebola virus (EBOV) is such kind of virus which is responsible for 23,825 cases and 9675 deaths worldwide only in 2014 and with an average diseases fatality rate between 25 % and 90 %. Although, medical technology has tried to handle the problems, there is no Food and Drug Administration (FDA)-approved therapeutics or vaccines available for the prevention, post exposure, or treatment of Ebola virus disease (EVD). METHODS: In the present study, we used the immunoinformatics approach to design a potential epitope-based vaccine against the RNA-dependent RNA polymerase-L of EBOV. BioEdit v7.2.3 sequence alignment editor, Jalview v2 and CLC Sequence Viewer v7.0.2 were used for the initial sequence analysis for securing the conservancy from the sequences. Later the Immune Epitope Database and Analysis Resource (IEDB-AR) was used for the identification of T-cell and B-cellepitopes associated with type I and II major histocompatibility complex molecules analysis. Finally, the population coverage analysis was employed. RESULTS: The core epitope “FRYEFTAPF” was found to be the most potential one, with 100 % conservancy among all the strains of EBOV. It also interacted with both type I and II major histocompatibility complex molecules and is considered as nonallergenic in nature. Finally, with impressive cumulative population coverage of 99.87 % for the both MHC-I and MHC-II class throughout the world population was found for the proposed epitope. CONCLUSION: To end, the projected peptide gave us a solid stand to propose for vaccine consideration and that might be experimented for its potency in eliciting immunity through humoral and cell mediated immune responses in vitro and in vivo. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40203-015-0011-4) contains supplementary material, which is available to authorized users.",2015 Aug 8,"['Oany, Arafat Rahman', 'Sharmin, Tahmina', 'Chowdhury, Afrin Sultana', 'Jyoti, Tahmina Pervin', 'Hasan, Md. Anayet']",In Silico Pharmacol,,,True
15f149f2f2ca015d5b8b5c6ef59595c907f4c01f,PMC,Insights into the respiratory tract microbiota of patients with cystic fibrosis during early Pseudomonas aeruginosa colonization,http://dx.doi.org/10.1186/s40064-015-1207-0,PMC4529844,26266076,CC BY,"Pseudomonasaeruginosa plays a major role in cystic fibrosis (CF) progression. Therefore, it is important to understand the initial steps of P. aeruginosa infection. The structure and dynamics of CF respiratory tract microbial communities during the early stages of P. aeruginosa colonization were characterized by pyrosequencing and cloning-sequencing. The respiratory microbiota showed high diversity, related to the young age of the CF cohort (mean age 10 years). Wide inter- and intra-individual variations were revealed. A common core microbiota of 5 phyla and 13 predominant genera was found, the majority of which were obligate anaerobes. A few genera were significantly more prevalent in patients never infected by P. aeruginosa. Persistence of an anaerobic core microbiota regardless of P. aeruginosa status suggests a major role of certain anaerobes in the pathophysiology of lung infections in CF. Some genera may be potential biomarkers of pulmonary infection state. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-015-1207-0) contains supplementary material, which is available to authorized users.",2015 Aug 9,"['Keravec, Marlène', 'Mounier, Jérôme', 'Prestat, Emmanuel', 'Vallet, Sophie', 'Jansson, Janet K', 'Burgaud, Gaëtan', 'Rosec, Sylvain', 'Gouriou, Stéphanie', 'Rault, Gilles', 'Coton, Emmanuel', 'Barbier, Georges', 'Héry-Arnaud, Geneviève']",Springerplus,,,False
1a3bac899966e4d132f98e04fbe6132170568e00,PMC,Insights into the respiratory tract microbiota of patients with cystic fibrosis during early Pseudomonas aeruginosa colonization,http://dx.doi.org/10.1186/s40064-015-1207-0,PMC4529844,26266076,CC BY,"Pseudomonasaeruginosa plays a major role in cystic fibrosis (CF) progression. Therefore, it is important to understand the initial steps of P. aeruginosa infection. The structure and dynamics of CF respiratory tract microbial communities during the early stages of P. aeruginosa colonization were characterized by pyrosequencing and cloning-sequencing. The respiratory microbiota showed high diversity, related to the young age of the CF cohort (mean age 10 years). Wide inter- and intra-individual variations were revealed. A common core microbiota of 5 phyla and 13 predominant genera was found, the majority of which were obligate anaerobes. A few genera were significantly more prevalent in patients never infected by P. aeruginosa. Persistence of an anaerobic core microbiota regardless of P. aeruginosa status suggests a major role of certain anaerobes in the pathophysiology of lung infections in CF. Some genera may be potential biomarkers of pulmonary infection state. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-015-1207-0) contains supplementary material, which is available to authorized users.",2015 Aug 9,"['Keravec, Marlène', 'Mounier, Jérôme', 'Prestat, Emmanuel', 'Vallet, Sophie', 'Jansson, Janet K', 'Burgaud, Gaëtan', 'Rosec, Sylvain', 'Gouriou, Stéphanie', 'Rault, Gilles', 'Coton, Emmanuel', 'Barbier, Georges', 'Héry-Arnaud, Geneviève']",Springerplus,,,False
d338fd85fb47b5cb4d62c6ec0b753f4596d5b515,PMC,Insights into the respiratory tract microbiota of patients with cystic fibrosis during early Pseudomonas aeruginosa colonization,http://dx.doi.org/10.1186/s40064-015-1207-0,PMC4529844,26266076,CC BY,"Pseudomonasaeruginosa plays a major role in cystic fibrosis (CF) progression. Therefore, it is important to understand the initial steps of P. aeruginosa infection. The structure and dynamics of CF respiratory tract microbial communities during the early stages of P. aeruginosa colonization were characterized by pyrosequencing and cloning-sequencing. The respiratory microbiota showed high diversity, related to the young age of the CF cohort (mean age 10 years). Wide inter- and intra-individual variations were revealed. A common core microbiota of 5 phyla and 13 predominant genera was found, the majority of which were obligate anaerobes. A few genera were significantly more prevalent in patients never infected by P. aeruginosa. Persistence of an anaerobic core microbiota regardless of P. aeruginosa status suggests a major role of certain anaerobes in the pathophysiology of lung infections in CF. Some genera may be potential biomarkers of pulmonary infection state. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-015-1207-0) contains supplementary material, which is available to authorized users.",2015 Aug 9,"['Keravec, Marlène', 'Mounier, Jérôme', 'Prestat, Emmanuel', 'Vallet, Sophie', 'Jansson, Janet K', 'Burgaud, Gaëtan', 'Rosec, Sylvain', 'Gouriou, Stéphanie', 'Rault, Gilles', 'Coton, Emmanuel', 'Barbier, Georges', 'Héry-Arnaud, Geneviève']",Springerplus,,,False
6d3e2a9b44f902aba943050ec1dbd4cd0b85309c,PMC,Insights into the respiratory tract microbiota of patients with cystic fibrosis during early Pseudomonas aeruginosa colonization,http://dx.doi.org/10.1186/s40064-015-1207-0,PMC4529844,26266076,CC BY,"Pseudomonasaeruginosa plays a major role in cystic fibrosis (CF) progression. Therefore, it is important to understand the initial steps of P. aeruginosa infection. The structure and dynamics of CF respiratory tract microbial communities during the early stages of P. aeruginosa colonization were characterized by pyrosequencing and cloning-sequencing. The respiratory microbiota showed high diversity, related to the young age of the CF cohort (mean age 10 years). Wide inter- and intra-individual variations were revealed. A common core microbiota of 5 phyla and 13 predominant genera was found, the majority of which were obligate anaerobes. A few genera were significantly more prevalent in patients never infected by P. aeruginosa. Persistence of an anaerobic core microbiota regardless of P. aeruginosa status suggests a major role of certain anaerobes in the pathophysiology of lung infections in CF. Some genera may be potential biomarkers of pulmonary infection state. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-015-1207-0) contains supplementary material, which is available to authorized users.",2015 Aug 9,"['Keravec, Marlène', 'Mounier, Jérôme', 'Prestat, Emmanuel', 'Vallet, Sophie', 'Jansson, Janet K', 'Burgaud, Gaëtan', 'Rosec, Sylvain', 'Gouriou, Stéphanie', 'Rault, Gilles', 'Coton, Emmanuel', 'Barbier, Georges', 'Héry-Arnaud, Geneviève']",Springerplus,,,True
c1590dca1224c338b4163beacf9a838e7caec9c8,PMC,Affect of Early Life Oxygen Exposure on Proper Lung Development and Response to Respiratory Viral Infections,http://dx.doi.org/10.3389/fmed.2015.00055,PMC4530667,26322310,CC BY,"Children born preterm often exhibit reduced lung function and increased severity of response to respiratory viruses, suggesting that premature birth has compromised proper development of the respiratory epithelium and innate immune defenses. Increasing evidence suggests that premature birth promotes aberrant lung development likely due to the neonatal oxygen transition occurring before pulmonary development has matured. Given that preterm infants are born at a point of time where their immune system is also still developing, early life oxygen exposure may also be disrupting proper development of innate immunity. Here, we review current literature in hopes of stimulating research that enhances understanding of how the oxygen environment at birth influences lung development and host defense. This knowledge may help identify those children at risk for disease and ideally culminate in the development of novel therapies that improve their health.",2015 Aug 10,"['Domm, William', 'Misra, Ravi S.', 'O’Reilly, Michael A.']",Front Med (Lausanne),,,True
cb820c7373e5c272cc31065db8579e927176be72,PMC,Striding Toward Malaria Elimination in China,http://dx.doi.org/10.4269/ajtmh.15-0391,PMC4530732,26078325,CC BY,,2015 Aug 5,"['Hsiang, Michelle S.', 'Gosling, Roly D.']",Am J Trop Med Hyg,,,True
9c2c85e5e00aed9437ada6a93643d1aa660b59c4,PMC,"Malaria in Zhejiang Province, China, from 2005 to 2014",http://dx.doi.org/10.4269/ajtmh.15-0080,PMC4530752,26078321,CC BY,"To summarize the changing epidemiological characteristics of malaria in Zhejiang Province, China, we collected data on malaria from the Chinese Notifiable Disease Reporting System (NDRS) and analyzed them. A total of 2,738 malaria cases were identified in Zhejiang Province from 2005 to 2014, of which 2,018 were male and 720 were female. Notably, only 7% of malaria cases were indigenous and the other cases were all imported. The number of malaria cases increased from 2005 to 2007, peaked in 2007, and then decreased from 2007 to 2011. There were no indigenous cases from 2012 to 2014. Of all cases, 68% of cases contracted Plasmodium vivax, 27% of cases contracted P. falciparum, and two cases contracted P. malariae. About 88% of malaria cases during 2005–2011 occurred yearly between May and October, but the number of malaria cases in different months during 2012–2014 was similar. The median age was 33 years, and 1,892 cases occurred in persons aged 20–50 years. The proportion of businessmen increased and the proportion of migrant laborers decreased in recent years. The median time from illness onset to confirmation of malaria cases was 5 days and it decreased from 2005 to 2014. Some epidemiological characteristics of malaria have changed, and businessmen are the emphases to surveillance in every month.",2015 Aug 5,"['Chen, Hualiang', 'Yao, Linong', 'Zhang, Lingling', 'Zhang, Xuan', 'Lu, Qiaoyi', 'Yu, Kegen', 'Ruan, Wei']",Am J Trop Med Hyg,,,True
5229d13f7a121dfc9a455d2ec0807e3966da3e19,PMC,NMR and MD Studies Reveal That the Isolated Dengue NS3 Protease Is an Intrinsically Disordered Chymotrypsin Fold Which Absolutely Requests NS2B for Correct Folding and Functional Dynamics,http://dx.doi.org/10.1371/journal.pone.0134823,PMC4530887,26258523,CC BY,"Dengue genome encodes a two component protease complex (NS2B-NS3pro) essential for the viral maturation/infectivity, thus representing a key drug target. Previously, due to its “complete insolubility”, the isolated NS3pro could not be experimentally studied and it remains elusive what structure it adopts without NS2B and why NS2B is indispensable. Here as facilitated by our previous discovery, the isolated NS3pro has been surprisingly deciphered by NMR to be the first intrinsically-disordered chymotrypsin-like fold, which exists in a loosely-packed state with non-native long-range interactions as revealed by paramagnetic relaxation enhancement (PRE). The disordered NS3pro appears to be needed for binding a human host factor to trigger the membrane remodeling. Moreover, we have in vitro refolded the NS3pro in complex with either NS2B (48–100) or the full-length NS2B (1–130) anchored into the LMPC micelle, and the two complexes have similar activities but different dynamics. We also performed molecular dynamics (MD) simulations and the results revealed that NS2B shows the highest structural fluctuations in the complex, thus providing the dynamic basis for the observation on its conformational exchange between open and closed states. Remarkably, the NS2B cofactor plays a central role in maintaining the correlated motion network required for the catalysis as we previously decoded for the SARS 3CL protease. Indeed, a truncated NS2B (48–100;Δ77–84) with the flexible loop deleted is able to trap the NS2B-NS3pro complex in a highly dynamic and catalytically-impotent state. Taken together, our study implies potential strategies to perturb the NS2B-NS3pro interface for design of inhibitors for treating dengue infection.",2015 Aug 10,"['Gupta, Garvita', 'Lim, Liangzhong', 'Song, Jianxing']",PLoS One,,,True
914636db7f8a6361126e805e4abd3c8a8d5ab31f,PMC,Challenges and Strategies of Laboratory Diagnosis for Newly Emerging Influenza Viruses in Taiwan: A Decade after SARS,http://dx.doi.org/10.1155/2015/805306,PMC4531154,26290876,CC BY,"Since the first case of severe acute respiratory syndrome (SARS) in Taiwan was identified in March 2003, viral respiratory infections, in particular the influenza virus, have become a national public health concern. Taiwan would face a serious threat of public health problems if another SARS epidemic overlapped with a flu outbreak. After SARS, the Taiwan Centers for Disease Control accelerated and strengthened domestic research on influenza and expanded the exchange of information with international counterparts. The capacity of influenza A to cross species barriers presents a potential threat to human health. Given the mutations of avian flu viruses such as H7N9, H6N1, and H10N8, all countries, including Taiwan, must equip themselves to face a possible epidemic or pandemic. Such preparedness requires global collaboration.",2015 Jul 28,"['Lin, Jih-Hui', 'Wu, Ho-Sheng']",Biomed Res Int,,,True
6d4c934e5babea34af1b80d784ce9422735c9dc4,PMC,Real-time digital pathogen surveillance — the time is now,http://dx.doi.org/10.1186/s13059-015-0726-x,PMC4531805,27391693,CC BY,"It is time to shake up public health surveillance. New technologies for sequencing, aided by friction-free approaches to data sharing, could have an impact on public health efforts.",2015 Jul 30,"['Gardy, Jennifer', 'Loman, Nicholas J.', 'Rambaut, Andrew']",Genome Biol,,,True
795bd84388973214e4b97ea23b80a9dc4e481117,PMC,E3 Ubiquitin Ligase NEDD4 Promotes Influenza Virus Infection by Decreasing Levels of the Antiviral Protein IFITM3,http://dx.doi.org/10.1371/journal.ppat.1005095,PMC4532365,26263374,CC BY,"Interferon (IFN)-induced transmembrane protein 3 (IFITM3) is a cell-intrinsic factor that limits influenza virus infections. We previously showed that IFITM3 degradation is increased by its ubiquitination, though the ubiquitin ligase responsible for this modification remained elusive. Here, we demonstrate that the E3 ubiquitin ligase NEDD4 ubiquitinates IFITM3 in cells and in vitro. This IFITM3 ubiquitination is dependent upon the presence of a PPxY motif within IFITM3 and the WW domain-containing region of NEDD4. In NEDD4 knockout mouse embryonic fibroblasts, we observed defective IFITM3 ubiquitination and accumulation of high levels of basal IFITM3 as compared to wild type cells. Heightened IFITM3 levels significantly protected NEDD4 knockout cells from infection by influenza A and B viruses. Similarly, knockdown of NEDD4 in human lung cells resulted in an increase in steady state IFITM3 and a decrease in influenza virus infection, demonstrating a conservation of this NEDD4-dependent IFITM3 regulatory mechanism in mouse and human cells. Consistent with the known association of NEDD4 with lysosomes, we demonstrate for the first time that steady state turnover of IFITM3 occurs through the lysosomal degradation pathway. Overall, this work identifies the enzyme NEDD4 as a new therapeutic target for the prevention of influenza virus infections, and introduces a new paradigm for up-regulating cellular levels of IFITM3 independently of IFN or infection.",2015 Aug 11,"['Chesarino, Nicholas M.', 'McMichael, Temet M.', 'Yount, Jacob S.']",PLoS Pathog,,,True
4518da3d4fdddd13a397a1fd68ce915512615db2,PMC,Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan,http://dx.doi.org/10.1371/journal.pone.0133910,PMC4532476,26263554,CC BY,"BACKGROUND: Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past. METHODS: Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved. RESULTS: The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells. CONCLUSION: These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.",2015 Aug 11,"['Li, Yao-Tsun', 'Ko, Hui-Ying', 'Lee, Chang-Chun David', 'Lai, Ching-Yu', 'Kao, Chuan-Liang', 'Yang, Chinglai', 'Wang, Won-Bo', 'King, Chwan-Chuen']",PLoS One,,,True
5138729644d04e24590ea0124ff60cdd896c0bad,PMC,Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan,http://dx.doi.org/10.1371/journal.pone.0133910,PMC4532476,26263554,CC BY,"BACKGROUND: Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past. METHODS: Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved. RESULTS: The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells. CONCLUSION: These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.",2015 Aug 11,"['Li, Yao-Tsun', 'Ko, Hui-Ying', 'Lee, Chang-Chun David', 'Lai, Ching-Yu', 'Kao, Chuan-Liang', 'Yang, Chinglai', 'Wang, Won-Bo', 'King, Chwan-Chuen']",PLoS One,,,False
695b24880d22f32b2f5648316d56d9e7bb26e0cb,PMC,Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan,http://dx.doi.org/10.1371/journal.pone.0133910,PMC4532476,26263554,CC BY,"BACKGROUND: Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past. METHODS: Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved. RESULTS: The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells. CONCLUSION: These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.",2015 Aug 11,"['Li, Yao-Tsun', 'Ko, Hui-Ying', 'Lee, Chang-Chun David', 'Lai, Ching-Yu', 'Kao, Chuan-Liang', 'Yang, Chinglai', 'Wang, Won-Bo', 'King, Chwan-Chuen']",PLoS One,,,False
1142b43a1c754a62675eeb7ae78cf4fa78bc60fa,PMC,Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan,http://dx.doi.org/10.1371/journal.pone.0133910,PMC4532476,26263554,CC BY,"BACKGROUND: Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past. METHODS: Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved. RESULTS: The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells. CONCLUSION: These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.",2015 Aug 11,"['Li, Yao-Tsun', 'Ko, Hui-Ying', 'Lee, Chang-Chun David', 'Lai, Ching-Yu', 'Kao, Chuan-Liang', 'Yang, Chinglai', 'Wang, Won-Bo', 'King, Chwan-Chuen']",PLoS One,,,False
f9e825f3e3cb781127402da99ebbc6e2a5ccbda1,PMC,Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan,http://dx.doi.org/10.1371/journal.pone.0133910,PMC4532476,26263554,CC BY,"BACKGROUND: Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past. METHODS: Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved. RESULTS: The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells. CONCLUSION: These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.",2015 Aug 11,"['Li, Yao-Tsun', 'Ko, Hui-Ying', 'Lee, Chang-Chun David', 'Lai, Ching-Yu', 'Kao, Chuan-Liang', 'Yang, Chinglai', 'Wang, Won-Bo', 'King, Chwan-Chuen']",PLoS One,,,False
b963e160bbcb75fc97ff2b69d0762d27343cb568,PMC,Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan,http://dx.doi.org/10.1371/journal.pone.0133910,PMC4532476,26263554,CC BY,"BACKGROUND: Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past. METHODS: Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved. RESULTS: The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells. CONCLUSION: These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.",2015 Aug 11,"['Li, Yao-Tsun', 'Ko, Hui-Ying', 'Lee, Chang-Chun David', 'Lai, Ching-Yu', 'Kao, Chuan-Liang', 'Yang, Chinglai', 'Wang, Won-Bo', 'King, Chwan-Chuen']",PLoS One,,,False
8b4973c7d257f7db1109925842617522a9256b3e,PMC,Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan,http://dx.doi.org/10.1371/journal.pone.0133910,PMC4532476,26263554,CC BY,"BACKGROUND: Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past. METHODS: Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved. RESULTS: The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells. CONCLUSION: These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.",2015 Aug 11,"['Li, Yao-Tsun', 'Ko, Hui-Ying', 'Lee, Chang-Chun David', 'Lai, Ching-Yu', 'Kao, Chuan-Liang', 'Yang, Chinglai', 'Wang, Won-Bo', 'King, Chwan-Chuen']",PLoS One,,,False
3e8286a0531a46c267f34d20e60a4754c2391a09,PMC,Central Hypoventilation: A Case Study of Issues Associated with Travel Medicine and Respiratory Infection,http://dx.doi.org/10.1155/2015/647139,PMC4532870,26294997,CC BY,"Aim. We presented the case of a child with central hypoventilation syndrome (CHS) to highlight issues that need to be considered in planning long-haul flight and problems that may arise during the flight. Case. The pediatric intensive care unit (PICU) received a child with central hypoventilation syndrome (Ondine's curse) on nocturnal ventilatory support who travelled to Hong Kong on a make-a-wish journey. He was diagnosed with central hypoventilation and had been well managed in Canada. During a long-haul aviation travel, he developed respiratory symptoms and desaturations. The child arrived in Hong Kong and his respiratory symptoms persisted. He was taken to a PICU for management. The child remained well and investigations revealed no pathogen to account for his respiratory infection. He went on with his make-a-wish journey. Conclusions. Various issues of travel medicine such as equipment, airline arrangement, in-flight ventilatory support, travel insurance, and respiratory infection are explored and discussed. This case illustrates that long-haul air travel is possible for children with respiratory compromise if anticipatory preparation is timely arranged.",2015 Jul 29,"['Hon, Kam Lun', 'Leung, Alexander K. C.', 'Li, Albert M. C.', 'Ng, Daniel K. K.']",Case Rep Pediatr,,,True
e88ddb14ceee73a1db00d2991c683b872e747b33,PMC,Bocavirus Infection in Otherwise Healthy Children with Respiratory Disease,http://dx.doi.org/10.1371/journal.pone.0135640,PMC4534143,26267139,CC BY,"To evaluate the role of human bocavirus (hBoV) as a causative agent of respiratory disease, the importance of the viral load in respiratory disease type and severity and the pathogenicity of the different hBoV species, we studied all hBoV-positive nasopharyngeal samples collected from children who attended an emergency room for a respiratory tract infection during three winters (2009–2010, 2011–2012, and 2013–2014). Human bocavirus was detected using the respiratory virus panel fast assay and real-time PCR. Of the 1,823 nasopharyngeal samples, 104 (5.7%) were positive for hBoV; a similar prevalence was observed in all three periods studied. Among hBoV-infected children, 53.8% were between 1–2 years old, and hBoV was detected alone in 57/104 (54.8%) cases. All of the detected hBoV strains belonged to genotype 1. The median hBoV load was significantly higher in samples containing strains with both the N546H and T590S mutations compared to other samples (p<0.05). Children with a single hBoV-1 infection more frequently had upper respiratory tract infections (URTIs) than those who were co-infected (37.0% vs 17.8%, respectively, p = 0.04). The duration of hospitalization was longer among children with high viral loads than that observed among children with low viral loads (8.0 ±2.2 days vs 5.0 ±1.5 days, respectively, p = 0.03), and the use of aerosol therapy was more frequent among children with high viral loads than among those with low viral loads (77.1% vs 55.7%, respectively, p = 0.04). This study shows that hBoV is a relatively uncommon but stable infectious agent in children and that hBoV1 seems to be the only strain detected in Italy in respiratory samples. From a clinical point of view, hBoV1 seems to have in the majority of healthy children relatively low clinical relevance. Moreover, the viral load influences only the duration of hospitalization and the use of aerosol therapy without any association with the site of the respiratory disease.",2015 Aug 12,"['Principi, Nicola', 'Piralla, Antonio', 'Zampiero, Alberto', 'Bianchini, Sonia', 'Umbrello, Giulia', 'Scala, Alessia', 'Bosis, Samantha', 'Fossali, Emilio', 'Baldanti, Fausto', 'Esposito, Susanna']",PLoS One,,,True
56e7f3e210952c559633020f5910284c76111fde,PMC,Detection and molecular characterisation of bovine corona and toroviruses from Croatian cattle,http://dx.doi.org/10.1186/s12917-015-0511-9,PMC4535285,26268320,CC BY,"BACKGROUND: Bovine coronavirus (BCoV) together with bovine torovirus (BToV), both members of the Coronaviridae family, order Nidovirales are the most common viral enteric pathogens. Although studied separately, their joint occurrence and the molecular diversity in cattle in Croatia have not been investigated. METHODS: A survey is carried out on 101 fecal samples from diarrheic young and adult cattle during the 3-year period from i) one large dairy herd, ii) four small herds and iii) three nasal and paired fecal samples from calves with symptoms of respiratory disease. Samples were submitted to RT-PCR and sequencing for BCoV Nucleocapsid gene, BCoV Spike gene and BToV Spike gene. RESULTS: BCoV was detected in 78.8 % of fecal samples from symptomatic cattle and three nasal and paired fecal samples from calves with respiratory symptoms. BToV was detected in 43.2 % of fecal samples from symptomatic cattle and a fecal sample from calves with respiratory symptoms. Molecular characterisation of those viruses revealed some nucleotide and aminoacid differences in relation to reference strains. CONCLUSIONS: BToV should be regarded as a relevant pathogen for cattle that plays a synergistic role in mixed enteric infections.",2015 Aug 13,"['Lojkić, Ivana', 'Krešić, Nina', 'Šimić, Ivana', 'Bedeković, Tomislav']",BMC Vet Res,,,True
06094b031f02c0307da315a1428394c2c075ff2a,PMC,"Complete Genome Sequence of Middle East Respiratory Syndrome Coronavirus KOR/KNIH/002_05_2015, Isolated in South Korea",http://dx.doi.org/10.1128/genomeA.00787-15,PMC4536669,26272558,CC BY,"The full genome sequence of a Middle East respiratory syndrome coronavirus (MERS-CoV) was identified from cultured and isolated in Vero cells. The viral genome sequence has high similarity to 53 human MERS-CoVs, ranging from 99.5% to 99.8% at the nucleotide level.",2015 Aug 13,"['Kim, You-Jin', 'Cho, Yong-Joon', 'Kim, Dae-Won', 'Yang, Jeong-Sun', 'Kim, Hak', 'Park, SungHan', 'Han, Young Woo', 'Yun, Mi-ran', 'Lee, Han Saem', 'Kim, A-Reum', 'Heo, Deok Rim', 'Kim, Joo Ae', 'Kim, Su Jin', 'Jung, Hee-Dong', 'Kim, Namil', 'Yoon, Seok-Hwan', 'Nam, Jeong-Gu', 'Kang, Hae Ji', 'Cheong, Hyang-Min', 'Lee, Joo-Shil', 'Chun, Jongsik', 'Kim, Sung Soon']",Genome Announc,,,True
60721983c03cfb1fd6e277fb6cc20bd117a3df80,PMC,Complete Genome Sequence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) from the First Imported MERS-CoV Case in China,http://dx.doi.org/10.1128/genomeA.00818-15,PMC4536671,26272560,CC BY,"On 26 May 2015, an imported Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in Guangdong Province, China, and found to be closely related to the MERS-CoV strain prevalent in South Korea. The full genome of the ChinaGD01 strain was sequenced and analyzed to investigate the epidemiology and evolution of MERS-CoV circulating in South Korea and China.",2015 Aug 13,"['Lu, Roujian', 'Wang, Yanqun', 'Wang, Wenling', 'Nie, Kai', 'Zhao, Yanjie', 'Su, Juan', 'Deng, Yao', 'Zhou, Weimin', 'Li, Yang', 'Wang, Huijuan', 'Wang, Wen', 'Ke, Changwen', 'Ma, Xuejun', 'Wu, Guizhen', 'Tan, Wenjie']",Genome Announc,,,True
c9cd7adce6639f51a4ee3e4bc7904eff851de25f,PMC,Complete Genome Sequence of the Porcine Epidemic Diarrhea Virus Variant Tottori2/JPN/2014,http://dx.doi.org/10.1128/genomeA.00877-15,PMC4536677,26272566,CC BY,"Porcine epidemic diarrhea virus (PEDV) is a cause of diarrhea outbreaks at swine farms, causing vomiting, severe diarrhea, and mortality in piglets. We sequenced and analyzed the complete genome of recently isolated strains. Tottori2/JPN/2014, one of the sequenced PEDV strains, had a unique large deletion in the S gene.",2015 Aug 13,"['Murakami, Satoshi', 'Miyazaki, Ayako', 'Takahashi, Osamu', 'Hashizume, Wataru', 'Hase, Yoichi', 'Ohashi, Seiichi', 'Suzuki, Tohru']",Genome Announc,,,True
cb763a61411514366d16bb2571461b6df1361517,PMC,Tropism and Induction of Cytokines in Human Embryonic-Stem Cells-Derived Neural Progenitors upon Inoculation with Highly- Pathogenic Avian H5N1 Influenza Virus,http://dx.doi.org/10.1371/journal.pone.0135850,PMC4537284,26274828,CC BY,"Central nervous system (CNS) dysfunction caused by neurovirulent influenza viruses is a dreaded complication of infection, and may play a role in some neurodegenerative conditions, such as Parkinson-like diseases and encephalitis lethargica. Although CNS infection by highly pathogenic H5N1 virus has been demonstrated, it is unknown whether H5N1 infects neural progenitor cells, nor whether such infection plays a role in the neuroinflammation and neurodegeneration. To pursue this question, we infected human neural progenitor cells (hNPCs) differentiated from human embryonic stem cells in vitro with H5N1 virus, and studied the resulting cytopathology, cytokine expression, and genes involved in the differentiation. Human embryonic stem cells (BG01) were maintained and differentiated into the neural progenitors, and then infected by H5N1 virus (A/Chicken/Thailand/CUK2/04) at a multiplicity of infection of 1. At 6, 24, 48, and 72 hours post-infection (hpi), cytopathic effects were observed. Then cells were characterized by immunofluorescence and electron microscopy, supernatants quantified for virus titers, and sampled cells studied for candidate genes.The hNPCs were susceptible to H5N1 virus infection as determined by morphological observation and immunofluorescence. The infection was characterized by a significant up-regulation of TNF-α gene expression, while expressions of IFN-α2, IFN-β1, IFN-γ and IL-6 remained unchanged compared to mock-infected controls. Moreover, H5N1 infection did not appear to alter expression of neuronal and astrocytic markers of hNPCs, such as β-III tubulin and GFAP, respectively. The results indicate that hNPCs support H5N1 virus infection and may play a role in the neuroinflammation during acute viral encephalitis.",2015 Aug 14,"['Pringproa, Kidsadagon', 'Rungsiwiwut, Ruttachuk', 'Tantilertcharoen, Rachod', 'Praphet, Reunkeaw', 'Pruksananonda, Kamthorn', 'Baumgärtner, Wolfgang', 'Thanawongnuwech, Roongroje']",PLoS One,,,True
023af2216525c16fa52a75b99cc91ebb03e93107,PMC,Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27,http://dx.doi.org/10.1038/srep13133,PMC4539535,26281793,CC BY,"The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans with an approximately 30% mortality rate. The envelope spike glycoprotein on the surface of MERS-CoV mediates receptor binding, membrane fusion, and viral entry. We previously reported two human monoclonal antibodies that target the receptor binding domain (RBD) of the spike and exhibit strong neutralization activity against live and pesudotyped MERS-CoV infection. Here we determined the crystal structure of MERS-CoV RBD bound to the Fab fragment of MERS-27 antibody at 3.20 Å resolution. The MERS-27 epitope in the RBD overlaps with the binding site of the MERS-CoV receptor DPP4. Further biochemical, viral entry, and neutralization analyses identified two critical residues in the RBD for both MERS-27 recognition and DPP4 binding. One of the residues, Trp535, was found to function as an anchor residue at the binding interface with MERS-27. Upon receptor binding, Trp535 interacts with the N-linked carbohydrate moiety of DPP4. Thus, MERS-27 inhibits MERS-CoV infection by directly blocking both protein-protein and protein-carbohydrate interactions between MERS-CoV RBD and DPP4. These results shed light on the molecular basis of MERS-27 neutralization and will assist in the optimization of MERS-27 as a tool to combat MERS-CoV infection.",2015 Aug 18,"['Yu, Xiaojuan', 'Zhang, Senyan', 'Jiang, Liwei', 'Cui, Ye', 'Li, Dongxia', 'Wang, Dongli', 'Wang, Nianshuang', 'Fu, Lili', 'Shi, Xuanlin', 'Li, Ziqiang', 'Zhang, Linqi', 'Wang, Xinquan']",Sci Rep,,,True
b8f48280d1c187776d6fc38cea706f8b5a269faf,PMC,Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27,http://dx.doi.org/10.1038/srep13133,PMC4539535,26281793,CC BY,"The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans with an approximately 30% mortality rate. The envelope spike glycoprotein on the surface of MERS-CoV mediates receptor binding, membrane fusion, and viral entry. We previously reported two human monoclonal antibodies that target the receptor binding domain (RBD) of the spike and exhibit strong neutralization activity against live and pesudotyped MERS-CoV infection. Here we determined the crystal structure of MERS-CoV RBD bound to the Fab fragment of MERS-27 antibody at 3.20 Å resolution. The MERS-27 epitope in the RBD overlaps with the binding site of the MERS-CoV receptor DPP4. Further biochemical, viral entry, and neutralization analyses identified two critical residues in the RBD for both MERS-27 recognition and DPP4 binding. One of the residues, Trp535, was found to function as an anchor residue at the binding interface with MERS-27. Upon receptor binding, Trp535 interacts with the N-linked carbohydrate moiety of DPP4. Thus, MERS-27 inhibits MERS-CoV infection by directly blocking both protein-protein and protein-carbohydrate interactions between MERS-CoV RBD and DPP4. These results shed light on the molecular basis of MERS-27 neutralization and will assist in the optimization of MERS-27 as a tool to combat MERS-CoV infection.",2015 Aug 18,"['Yu, Xiaojuan', 'Zhang, Senyan', 'Jiang, Liwei', 'Cui, Ye', 'Li, Dongxia', 'Wang, Dongli', 'Wang, Nianshuang', 'Fu, Lili', 'Shi, Xuanlin', 'Li, Ziqiang', 'Zhang, Linqi', 'Wang, Xinquan']",Sci Rep,,,False
2fe87abe58e092dfdabc0599ce8b31df6e49d4db,PMC,Results of an online questionnaire to survey calf management practices on dairy cattle breeding farms in Austria and to estimate differences in disease incidences depending on farm structure and management practices,http://dx.doi.org/10.1186/s13028-015-0134-y,PMC4539725,26282551,CC BY,"BACKGROUND: Calf disease may result in great economic losses. To implement prevention strategies it is important to gain information on management and to point out risk factors. The objective of this internet based survey was to describe calf management practices on registered dairy breeding farms in Austria and to estimate differences in calf disease incidences depending on farm structure and management practices. RESULTS: A total of 1287 questionnaires were finally analysed (response rate 12.2 %). Herd characteristics and regional distribution of farms indicated that this survey gives a good overview on calf management practices on registered dairy farms in Austria. The median number of cows per farm was 20 (interquartile range 13–30). Significant differences regarding farm characteristics and calf management between small and large farms (≤20 vs >20 cows) were present. Only 2.8 % of farmers tested first colostrum quality by use of a hydrometer. Storing frozen colostrum was more prevalent on large farms (80.8 vs 64.2 %). On 85.1 % of the farms, whole milk, including waste milk, was fed to the calves. Milk replacer and waste milk were more often used on large farms. In accordance with similar studies from other countries, calf diarrhoea was indicated as the most prevalent disease. Multivariable logistic regression analysis revealed that herd size was associated with calf diarrhoea and calf respiratory tract disease, with higher risk of disease on large farms. Furthermore, feeding waste milk to the calves was associated with increasing calf diarrhoea incidence on farm. In the final model with calf respiratory tract disease as outcome, respondents from organic farms reported less often a respiratory tract disease incidence of over 10 % compared with conventional farms [odds ratio (OR) 0.40, 95 % confidence interval (CI) 0.21–0.75] and farmers that housed calves individually or in groups after birth significantly reported more often to have an incidence of respiratory tract disease >10 % compared with farms where all calves were housed individually (OR 2.28, 95 % CI 1.16–4.48). CONCLUSION: The results obtained in this study provide an overview on calf management on dairy breeding farms in Austria and may help to further point out areas to be improved on farm. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-015-0134-y) contains supplementary material, which is available to authorized users.",2015 Aug 19,"['Klein-Jöbstl, Daniela', 'Arnholdt, Tim', 'Sturmlechner, Franz', 'Iwersen, Michael', 'Drillich, Marc']",Acta Vet Scand,,,False
d0812df257e4fb4f247f98f53298adea60585674,PMC,Results of an online questionnaire to survey calf management practices on dairy cattle breeding farms in Austria and to estimate differences in disease incidences depending on farm structure and management practices,http://dx.doi.org/10.1186/s13028-015-0134-y,PMC4539725,26282551,CC BY,"BACKGROUND: Calf disease may result in great economic losses. To implement prevention strategies it is important to gain information on management and to point out risk factors. The objective of this internet based survey was to describe calf management practices on registered dairy breeding farms in Austria and to estimate differences in calf disease incidences depending on farm structure and management practices. RESULTS: A total of 1287 questionnaires were finally analysed (response rate 12.2 %). Herd characteristics and regional distribution of farms indicated that this survey gives a good overview on calf management practices on registered dairy farms in Austria. The median number of cows per farm was 20 (interquartile range 13–30). Significant differences regarding farm characteristics and calf management between small and large farms (≤20 vs >20 cows) were present. Only 2.8 % of farmers tested first colostrum quality by use of a hydrometer. Storing frozen colostrum was more prevalent on large farms (80.8 vs 64.2 %). On 85.1 % of the farms, whole milk, including waste milk, was fed to the calves. Milk replacer and waste milk were more often used on large farms. In accordance with similar studies from other countries, calf diarrhoea was indicated as the most prevalent disease. Multivariable logistic regression analysis revealed that herd size was associated with calf diarrhoea and calf respiratory tract disease, with higher risk of disease on large farms. Furthermore, feeding waste milk to the calves was associated with increasing calf diarrhoea incidence on farm. In the final model with calf respiratory tract disease as outcome, respondents from organic farms reported less often a respiratory tract disease incidence of over 10 % compared with conventional farms [odds ratio (OR) 0.40, 95 % confidence interval (CI) 0.21–0.75] and farmers that housed calves individually or in groups after birth significantly reported more often to have an incidence of respiratory tract disease >10 % compared with farms where all calves were housed individually (OR 2.28, 95 % CI 1.16–4.48). CONCLUSION: The results obtained in this study provide an overview on calf management on dairy breeding farms in Austria and may help to further point out areas to be improved on farm. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-015-0134-y) contains supplementary material, which is available to authorized users.",2015 Aug 19,"['Klein-Jöbstl, Daniela', 'Arnholdt, Tim', 'Sturmlechner, Franz', 'Iwersen, Michael', 'Drillich, Marc']",Acta Vet Scand,,,True
384cdcda67c8a385d6a571ba5f9fb09e16d130b5,PMC,Porcine epidemic diarrhea virus inhibits dsRNA-induced interferon-β production in porcine intestinal epithelial cells by blockade of the RIG-I-mediated pathway,http://dx.doi.org/10.1186/s12985-015-0345-x,PMC4539884,26283628,CC BY,"BACKGROUND: The lack of optimal porcine cell lines has severely impeded the study and progress in elucidation of porcine epidemic diarrhea virus (PEDV) pathogenesis. Vero cell, an African green monkey kidney cell line, was often used to isolate and propagate PEDV. Nonetheless, the target cells of PEDV in vivo are intestinal epithelial cells, during infection, intestinal epithelia would be damaged and resulted in digestive disorders. The immune functions of porcine epithelial cells and interactions with other immune cell populations display a number of differences compared to other species. Type I interferon (IFN) plays an important role in antiviral immune response. Limited reports showed that PEDV could inhibit type I interferon production. In this study, porcine small intestinal epithelial cells (IECs), the target cells of PEDV, were used as the infection model in vitro to identify the possible molecular mechanisms of PEDV-inhibition IFN-β production. RESULTS: PEDV not only failed to induce IFN-β expression, but also inhibited dsRNA-mediated IFN-β production in IECs. As the key IFN-β transcription factors, we found that dsRNA-induced activation of IFN regulatory factor 3 (IRF-3) was inhibited after PEDV infection, but not nuclear factor-kappaB (NF-κB). To identify the mechanism of PEDV intervention with dsRNA-mediated IFN-β expression more accurately, the role of individual molecules of RIG-I signaling pathway were investigated. In the upstream of IRF-3, TANK-binding kinase 1 (TBK1)-or inhibitor of κB kinase-ε (IKKε)-mediated IFN-β production was not blocked by PEDV, while RIG-I-and its adapter molecule IFN-β promoter stimulator 1 (IPS-1)-mediated IFN-β production were completely inhibited after PEDV infection. CONCLUSION: Taken together, our data demonstrated for the first time that PEDV infection of its target cell line, IECs, inhibited dsRNA-mediated IFN-β production by blocking the activation of IPS-1 in RIG-I-mediated pathway. Our studies offered new visions in understanding of the interaction between PEDV and host innate immune system.",2015 Aug 18,"['Cao, Liyan', 'Ge, Xuying', 'Gao, Yu', 'Herrler, Georg', 'Ren, Yudong', 'Ren, Xiaofeng', 'Li, Guangxing']",Virol J,,,True
3fe17722a3541e556994dcad8f8d173be7f3ea88,PMC,"Comparative Analysis of Transcriptional Profiles of Adult Schistosoma japonicum from Different Laboratory Animals and the Natural Host, Water Buffalo",http://dx.doi.org/10.1371/journal.pntd.0003993,PMC4540470,26285138,CC BY,"BACKGROUND: Schistosomiasis is one of the most widely distributed parasitic diseases in the world. Schistosoma japonicum, a zoonotic parasite with a wide range of mammalian hosts, is one of the major pathogens of this disease. Although numerous studies on schistosomiasis japonica have been performed using laboratory animal models, systematic comparative analysis of whole-genome expression profiles in parasites from different laboratory animals and nature mammalian hosts is lacking to date. METHODOLOGY/PRINCIPAL FINDINGS: Adult schistosomes were obtained from laboratory animals BALB/c mice, C57BL/6 mice, New Zealand white rabbits and the natural host, water buffaloes. The gene expression profiles of schistosomes from these animals were obtained and compared by genome-wide oligonucleotide microarray analysis. The results revealed that the gene expression profiles of schistosomes from different laboratory animals and buffaloes were highly consistent (r>0.98) genome-wide. Meanwhile, a total of 450 genes were identified to be differentially expressed in schistosomes which can be clustered into six groups. Pathway analysis revealed that these genes were mainly involved in multiple signal transduction pathways, amino acid, energy, nucleotide and lipid metabolism. We also identified a group of 1,540 abundantly and stably expressed gene products in adult worms, including a panel of 179 Schistosoma- or Platyhelminthes-specific genes that may be essential for parasitism and may be regarded as novel potential anti-parasite intervention targets for future research. CONCLUSIONS/SIGNIFICANCE: This study provides a comprehensive database of gene expression profiles of schistosomes derived from different laboratory animals and water buffaloes. An expanded number of genes potentially affecting the development of schistosomes in different animals were identified. These findings lay the foundation for schistosomiasis research in different laboratory animals and natural hosts at the transcriptional level and provide a valuable resource for screening anti-schistosomal intervention targets.",2015 Aug 18,"['Liu, Shuai', 'Zhou, Xiaosu', 'Piao, Xianyu', 'Wu, Chuang', 'Hou, Nan', 'Chen, Qijun']",PLoS Negl Trop Dis,,,True
f2fcc16391f946c99717b63ec9a24e5384aac381,PMC,Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy,http://dx.doi.org/10.1038/srep13028,PMC4541410,26286358,CC BY,"Enfuvirtide (T20), is the first HIV fusion inhibitor approved for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, its clinical application is limited because of short half-life, drug resistance and cross-reactivity with the preexisting antibodies in HIV-infected patients. Using an artificial peptide strategy, we designed a peptide with non-native protein sequence, AP3, which exhibited potent antiviral activity against a broad spectrum of HIV-1 strains, including those resistant to T20, and had remarkably longer in vivo half-life than T20. While the preexisting antibodies in HIV-infected patients significantly suppressed T20’s antiviral activity, these antibodies neither recognized AP3, nor attenuated its anti-HIV-1 activity. Structurally different from T20, AP3 could fold into single-helix and interact with gp41 NHR. The two residues, Met and Thr, at the N-terminus of AP3 form a hook-like structure to stabilize interaction between AP3 and NHR helices. Therefore, AP3 has potential for further development as a new HIV fusion inhibitor with improved antiviral efficacy, resistance profile and pharmacological properties over enfuvirtide. Meanwhile, this study highlighted the advantages of artificially designed peptides, and confirmed that this strategy could be used in developing artificial peptide-based viral fusion inhibitors against HIV and other enveloped viruses.",2015 Aug 19,"['Zhu, Xiaojie', 'Zhu, Yun', 'Ye, Sheng', 'Wang, Qian', 'Xu, Wei', 'Su, Shan', 'Sun, Zhiwu', 'Yu, Fei', 'Liu, Qi', 'Wang, Chao', 'Zhang, Tianhong', 'Zhang, Zhenqing', 'Zhang, Xiaoyan', 'Xu, Jianqing', 'Du, Lanying', 'Liu, Keliang', 'Lu, Lu', 'Zhang, Rongguang', 'Jiang, Shibo']",Sci Rep,,,True
841893d64abe4ad83bfc1bb4542388ad0ad03534,PMC,Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy,http://dx.doi.org/10.1038/srep13028,PMC4541410,26286358,CC BY,"Enfuvirtide (T20), is the first HIV fusion inhibitor approved for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, its clinical application is limited because of short half-life, drug resistance and cross-reactivity with the preexisting antibodies in HIV-infected patients. Using an artificial peptide strategy, we designed a peptide with non-native protein sequence, AP3, which exhibited potent antiviral activity against a broad spectrum of HIV-1 strains, including those resistant to T20, and had remarkably longer in vivo half-life than T20. While the preexisting antibodies in HIV-infected patients significantly suppressed T20’s antiviral activity, these antibodies neither recognized AP3, nor attenuated its anti-HIV-1 activity. Structurally different from T20, AP3 could fold into single-helix and interact with gp41 NHR. The two residues, Met and Thr, at the N-terminus of AP3 form a hook-like structure to stabilize interaction between AP3 and NHR helices. Therefore, AP3 has potential for further development as a new HIV fusion inhibitor with improved antiviral efficacy, resistance profile and pharmacological properties over enfuvirtide. Meanwhile, this study highlighted the advantages of artificially designed peptides, and confirmed that this strategy could be used in developing artificial peptide-based viral fusion inhibitors against HIV and other enveloped viruses.",2015 Aug 19,"['Zhu, Xiaojie', 'Zhu, Yun', 'Ye, Sheng', 'Wang, Qian', 'Xu, Wei', 'Su, Shan', 'Sun, Zhiwu', 'Yu, Fei', 'Liu, Qi', 'Wang, Chao', 'Zhang, Tianhong', 'Zhang, Zhenqing', 'Zhang, Xiaoyan', 'Xu, Jianqing', 'Du, Lanying', 'Liu, Keliang', 'Lu, Lu', 'Zhang, Rongguang', 'Jiang, Shibo']",Sci Rep,,,False
239ea9fe738d669e1d479ec1471d33f1f271a4f8,PMC,"One health, multiple challenges: The inter-species transmission of influenza A virus",http://dx.doi.org/10.1016/j.onehlt.2015.03.001,PMC4542011,26309905,CC BY,"Influenza A viruses are amongst the most challenging viruses that threaten both human and animal health. Influenza A viruses are unique in many ways. Firstly, they are unique in the diversity of host species that they infect. This includes waterfowl (the original reservoir), terrestrial and aquatic poultry, swine, humans, horses, dog, cats, whales, seals and several other mammalian species. Secondly, they are unique in their capacity to evolve and adapt, following crossing the species barrier, in order to replicate and spread to other individuals within the new species. Finally, they are unique in the frequency of inter-species transmission events that occur. Indeed, the consequences of novel influenza virus strain in an immunologically naïve population can be devastating. The problems that influenza A viruses present for human and animal health are numerous. For example, influenza A viruses in humans represent a major economic and disease burden, whilst the poultry industry has suffered colossal damage due to repeated outbreaks of highly pathogenic avian influenza viruses. This review aims to provide a comprehensive overview of influenza A viruses by shedding light on interspecies virus transmission and summarising the current knowledge regarding how influenza viruses can adapt to a new host.",2015 Mar 26,"['Short, Kirsty R.', 'Richard, Mathilde', 'Verhagen, Josanne H.', 'van Riel, Debby', 'Schrauwen, Eefje J.A.', 'van den Brand, Judith M.A.', 'Mänz, Benjamin', 'Bodewes, Rogier', 'Herfst, Sander']",One Health,,,False
7a573001d0844b483871d264983ef4a6d9fde937,PMC,"Improving health aid for a better planet: The planning, monitoring and evaluation tool (PLANET)",http://dx.doi.org/10.7189/jogh.05.020404,PMC4544236,26322228,CC BY,"BACKGROUND: International development assistance for health (DAH) quadrupled between 1990 and 2012, from US$ 5.6 billion to US$ 28.1 billion. This generates an increasing need for transparent and replicable tools that could be used to set investment priorities, monitor the distribution of funding in real time, and evaluate the impact of those investments. METHODS: In this paper we present a methodology that addresses these three challenges. We call this approach PLANET, which stands for planning, monitoring and evaluation tool. Fundamentally, PLANET is based on crowdsourcing approach to obtaining information relevant to deployment of large–scale programs. Information is contributed in real time by a diverse group of participants involved in the program delivery. FINDINGS: PLANET relies on real–time information from three levels of participants in large–scale programs: funders, managers and recipients. At each level, information is solicited to assess five key risks that are most relevant to each level of operations. The risks at the level of funders involve systematic neglect of certain areas, focus on donor’s interests over that of program recipients, ineffective co–ordination between donors, questionable mechanisms of delivery and excessive loss of funding to “middle men”. At the level of managers, the risks are corruption, lack of capacity and/or competence, lack of information and /or communication, undue avoidance of governmental structures / preference to non–governmental organizations and exclusion of local expertise. At the level of primary recipients, the risks are corruption, parallel operations / “verticalization”, misalignment with local priorities and lack of community involvement, issues with ethics, equity and/or acceptability, and low likelihood of sustainability beyond the end of the program’s implementation. INTERPRETATION: PLANET is intended as an additional tool available to policy–makers to prioritize, monitor and evaluate large–scale development programs. In this, it should complement tools such as LiST (for health care/interventions), EQUIST (for health care/interventions) and CHNRI (for health research), which also rely on information from local experts and on local context to set priorities in a transparent, user–friendly, replicable, quantifiable and specific, algorithmic–like manner.",,"['Sridhar, Devi', 'Car, Josip', 'Chopra, Mickey', 'Campbell, Harry', 'Woods, Ngaire', 'Rudan, Igor']",J Glob Health.; 5(2):020404,,,True
a4c922f362c4d59ebe0b890776670e406d9dc985,PMC,"The Fecal Virome of Children with Hand, Foot, and Mouth Disease that Tested PCR Negative for Pathogenic Enteroviruses",http://dx.doi.org/10.1371/journal.pone.0135573,PMC4545796,26288145,CC BY,"Hand, foot, and mouth disease (HFMD) affects infant and young children. A viral metagenomic approach was used to identify the eukaryotic viruses in fecal samples from 29 Thai children with clinical diagnosis of HFMD collected during the 2012 outbreak. These children had previously tested negative by PCR for enterovirus 71 and coxsackievirus A16 and A6. Deep sequencing revealed nine virus families: Picornaviridae, Astroviridae, Parvoviridae, Caliciviridae, Paramyxoviridae, Adenoviridae, Reoviridae, Picobirnaviridae, and Polyomaviridae. The highest number of viral sequences belonged to human rhinovirus C, astrovirus-MLB2, and coxsackievirus A21. Our study provides an overview of virus community and highlights a broad diversity of viruses found in feces from children with HFMD.",2015 Aug 19,"['Linsuwanon, Piyada', 'Poovorawan, Yong', 'Li, Linlin', 'Deng, Xutao', 'Vongpunsawad, Sompong', 'Delwart, Eric']",PLoS One,,,True
850087dea2553c4099418c170742e85fcc4a5feb,PMC,"Concentration, Size Distribution, and Infectivity of Airborne Particles Carrying Swine Viruses",http://dx.doi.org/10.1371/journal.pone.0135675,PMC4545937,26287616,CC BY,"When pathogens become airborne, they travel associated with particles of different size and composition. Particle size determines the distance across which pathogens can be transported, as well as the site of deposition and the survivability of the pathogen. Despite the importance of this information, the size distribution of particles bearing viruses emitted by infectious animals remains unknown. In this study we characterized the concentration and size distribution of inhalable particles that transport influenza A virus (IAV), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine epidemic diarrhea virus (PEDV) generated by acutely infected pigs and assessed virus viability for each particle size range. Aerosols from experimentally infected pigs were sampled for 24 days using an Andersen cascade impactor able to separate particles by size (ranging from 0.4 to 10 micrometer (μm) in diameter). Air samples collected for the first 9, 20 and the last 3 days of the study were analyzed for IAV, PRRSV and PEDV, respectively, using quantitative reverse transcription polymerase chain reaction (RT-PCR) and quantified as geometric mean copies/m(3) within each size range. IAV was detected in all particle size ranges in quantities ranging from 5.5x10(2) (in particles ranging from 1.1 to 2.1μm) to 4.3x10(5) RNA copies/m(3) in the largest particles (9.0–10.0μm). PRRSV was detected in all size ranges except particles between 0.7 and 2.1μm in quantities ranging from 6x10(2) (0.4–0.7μm) to 5.1x10(4) RNA copies/m(3) (9.0–10.0μm). PEDV, an enteric virus, was detected in all particle sizes and in higher quantities than IAV and PRRSV (p < 0.0001) ranging from 1.3x10(6) (0.4–0.7μm) to 3.5x10(8) RNA copies/m(3) (9.0–10.0μm). Infectious status was demonstrated for the 3 viruses, and in the case of IAV and PRRSV, viruses were isolated from particles larger than 2.1μm. In summary, our results indicated that airborne PEDV, IAV and PRRSV can be found in a wide range of particle sizes. However, virus viability is particle size dependent.",2015 Aug 19,"['Alonso, Carmen', 'Raynor, Peter C.', 'Davies, Peter R.', 'Torremorell, Montserrat']",PLoS One,,,True
78646cec8be584199a96490a43bf47b2fd542f63,PMC,Burden of Illness in UK Subjects with Reported Respiratory Infections Vaccinated or Unvaccinated against Influenza: A Retrospective Observational Study,http://dx.doi.org/10.1371/journal.pone.0134928,PMC4546056,26287532,CC BY,"OBJECTIVE: Detailed data are lacking on influenza burden in the United Kingdom (UK). The objective of this study was to estimate the disease burden associated with influenza-like illness (ILI) in the United Kingdom stratified by age, risk and influenza vaccination status. METHODS: This retrospective, cross-sectional, exploratory, observational study used linked data from the General Practice Research Database and the Hospital Episode Statistics databases to estimate resource use and cost associated with ILI in the UK. RESULTS: Data were included from 156,193 patients with ≥1 general practitioner visit with ILI. There were 21,518 high-risk patients, of whom 12,514 (58.2%) were vaccinated and 9,004 (41.8%) were not vaccinated, and 134,675 low-risk patients, of whom 17,482 (13.0%) were vaccinated and 117,193 (87.0%) were not vaccinated. High-risk vaccinated patients were older (p<0.001) and had more risk conditions (p<0.001). High-risk (odds ratio [OR] 2.16) or vaccinated (OR 1.19) patients had a higher probability of >1 general practitioner visit compared with low-risk and unvaccinated patients. Patients who were high-risk and vaccinated had a reduced risk of >1 general practitioner visit (OR 0.82; p<0.001). High-risk individuals who were also vaccinated had a lower probability of ILI-related hospitalisation than individuals who were high-risk or vaccinated alone (OR 0.59). In people aged ≥65 years, the mortality rate was lower in vaccinated than unvaccinated individuals (OR 0.75). The cost of ILI-related GP visits and hospital admissions in the UK over the study period in low-risk vaccinated patients was £27,391,142 and £141,932,471, respectively. In low-risk unvaccinated patients the corresponding values were £168,318,709 and £112,534,130, respectively. CONCLUSIONS: Although vaccination rates in target groups have increased, many people are still not receiving influenza vaccination, and the burden of ILI in the United Kingdom remains substantial. Improving influenza vaccination uptake may have the potential to reduce this burden.",2015 Aug 19,"['Pockett, Rhys D.', 'Watkins, John', 'McEwan, Phil', 'Meier, Genevieve']",PLoS One,,,True
555559ac51210f5ee896ad5d45a6790d52a3e4d1,PMC,Determinants of emergency response responsibility perceptions in the local public health workforce after China’s health sector restructuring,http://dx.doi.org/10.1186/s12913-015-1003-0,PMC4546225,26293247,CC BY,"BACKGROUND: Local health departments are the backbone of public health emergency (PHE) response plans. The front line of emergency response preparedness is people. Role perceptions of individual staff members of a given organization strongly affect response probability and performance. Therefore, the aim of this study was to determine local public health employees’ perceptions of emergency response responsibilities, identify factors that influence their perception, and indicate the challenges and bottlenecks of PHE response in the Health Inspection Institution (HII) after its separation from China’s multiple Centers for Disease Control and Prevention (CDC). METHODS: We used a stratified randomized sample survey to examine HII workers’ knowledge of their own duties concerning PHE response in 17 facilities in Heilongjiang, a province in northeastern China. Data were collected from May to July 2010 using a 9-item combined question inquiring about the workers’ statutory duties. RESULTS: Of 348 administered surveys, 309 were returned for an overall response rate of 88.8 %. Overall, the correct recognition rate of PHE responsibilities was low. Some HII workers were confused about their responsibilities required by law, regulations, and emergency response plans. A quarter of all the respondents had the lowest knowledge for PHE responsibilities. Factors influencing their perceptions of responsibilities were department, work experience in a CDC, and PHE response experience. CONCLUSIONS: To improve preparedness for a PHE, efforts are needed to train, support, and monitor the workers’ knowledge and competencies in PHEs as part of an organizational change; the worker’s knowledge of their responsibilities should be measured and used as an indicator of preparedness for a PHE, and training should be undertaken where there are deficiencies. Management should also encourage workers in the departments of food hygiene/school health surveillance to be more involved in PHE preparedness and response issues.",2015 Aug 21,"['Jiao, Mingli', 'Ning, Ning', 'Wu, Qunhong', 'Peters, David H.', 'Hao, Yanhua', 'Li, Ye', 'Wei, Xingang', 'Kang, Zheng']",BMC Health Serv Res,,,True
fad38d4f310922f5af4326b319cfaf1eb8f70282,PMC,"Japanese Encephalitis in Assam, India: Need to Increase Healthcare Workers’ Understanding to Improve Health Care",http://dx.doi.org/10.1371/journal.pone.0135767,PMC4546657,26296212,CC BY,"INTRODUCTION: Japanese encephalitis (JE) is a major cause of high morbidity and mortality in several states across India. However, in 2014, a sharp rise was observed in the number of cases of JE in north-eastern Assam state, and 51% of the total cases of JE in India were reported from the Assam in the same year. In this regard, a study was conducted to evaluate the knowledge and attitudes of healthcare workers in Darrang, a district of Assam highly affected by JE. METHODS: A cross sectional study was conducted for 2 months among HCWs in the major district hospital of Darrang, Assam. A pre-tested, self-administered questionnaire was used to collect data from the participants. Convenience sampling approach was used to collect data from different departments of the hospitals. Descriptive and logistic regression analyses were used to express the results. RESULTS: The knowledge of HCWs regarding JE was poor with a mean knowledge score of 11.02±2.39 (out of 17), while their attitudes were positive with a mean attitudes score of 43.16± 2.47 (ranging from 13 to 52). Overall, 40.4% and 74.3% of participants demonstrated good knowledge and positive attitudes respectively. Cut-off score for good knowledge and positive attitudes toward JE was set as ≥12 and >40 respectively. Older participants (40–49 years) and experienced workers (>10 years) were significantly associated with good knowledge as compared to their referent group (p<0.05), while knowledge of nurses and other orderlies were significantly lower than physicians (p<0.01). Similar factors were associated with the positive attitudes of the participants with the exception of experience. Television was the major source of information regarding JE reported by HCWs (79%). CONCLUSION: Although the knowledge was not optimized, HCWs exhibited positive attitudes towards JE. Future research is required to design, implement and evaluate interventions to improve the knowledge of JE among HCWs.",2015 Aug 21,"['Ahmad, Akram', 'Khan, Muhammad Umair', 'Gogoi, Lakhya Jyoti', 'Kalita, Manabendra', 'Sikdar, Atul Prasad', 'Pandey, Sureshwar', 'Dhingra, Sameer']",PLoS One,,,True
4c4dd391e165ce712cb8871ce3082927bbf21ec9,PMC,Detection of Cytomegalovirus Antibodies Using a Biosensor Based on Imaging Ellipsometry,http://dx.doi.org/10.1371/journal.pone.0136253,PMC4546680,26295458,CC BY,"BACKGROUND: Cytomegalovirus (CMV) is the most common infectious cause of mental disability in newborns in developed countries. There is an urgent need to establish an early detection and high-throughput screening method for CMV infection using portable detection devices. METHODS: An antibody analysis method is reported for the detection and identification of CMV antibodies in serum using a biosensor based on high spatial resolution imaging ellipsometry (BIE). CMV antigen (CMV-3A) was immobilized on silicon wafers and used to capture CMV antibodies in serum. An antibody against human immunoglobulin G (anti-IgG) was used to confirm the IgG antibody against CMV captured by the CMV-3A. RESULTS: Our results show that this assay is rapid and specific for the identification of IgG antibody against CMV. Further, patient serum was quantitatively assessed using the standard curve method, and the quantitative results were in agreement with the enzyme-linked immunosorbent assay. The CMV antibody detection sensitivity of BIE reached 0.01 IU/mL. CONCLUSIONS: This novel biosensor may be a valuable diagnostic tool for analysis of IgG antibody against CMV during CMV infection screening.",2015 Aug 21,"['Sun, Hongliu', 'Qi, Cai', 'Niu, Yu', 'Kang, Tengfei', 'Wei, Yongxin', 'Jin, Gang', 'Dong, Xianzhi', 'Wang, Chunhua', 'Zhu, Wei']",PLoS One,,,True
7aea98cf7d30beea6043c5e62be3dafce08bdc0e,PMC,Non-immune immunoglobulins shield Schistosoma japonicum from host immunorecognition,http://dx.doi.org/10.1038/srep13434,PMC4547136,26299686,CC BY,"Schistosomiasis is a major human parasitic disease with a global impact. Schistosoma japonicum, the most difficult to control, can survive within host veins for decades. Mechanisms of immune evasion by the parasite, including antigenic variation and surface masking, have been implicated but not well defined. In this study, we defined the immunoglobulin-binding proteomes of S. japonicum using human IgG, IgM, and IgE as the molecular bait for affinity purification, followed by protein identification by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Several proteins situated at the tegument of S. japonicum were able to nonselectively bind to the Fc domain of host immunoglobulins, indicating a mechanism for the avoidance of host immune attachment and recognition. The profile of the immunoglobulin-binding proteomes provides further clues for immune evasion mechanisms adopted by S. japonicum.",2015 Aug 24,"['Wu, Chuang', 'Hou, Nan', 'Piao, Xianyu', 'Liu, Shuai', 'Cai, Pengfei', 'Xiao, Yan', 'Chen, Qijun']",Sci Rep,,,True
634c299b334104ab3b8be50713f7521b9eb06d4a,PMC,Non-immune immunoglobulins shield Schistosoma japonicum from host immunorecognition,http://dx.doi.org/10.1038/srep13434,PMC4547136,26299686,CC BY,"Schistosomiasis is a major human parasitic disease with a global impact. Schistosoma japonicum, the most difficult to control, can survive within host veins for decades. Mechanisms of immune evasion by the parasite, including antigenic variation and surface masking, have been implicated but not well defined. In this study, we defined the immunoglobulin-binding proteomes of S. japonicum using human IgG, IgM, and IgE as the molecular bait for affinity purification, followed by protein identification by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Several proteins situated at the tegument of S. japonicum were able to nonselectively bind to the Fc domain of host immunoglobulins, indicating a mechanism for the avoidance of host immune attachment and recognition. The profile of the immunoglobulin-binding proteomes provides further clues for immune evasion mechanisms adopted by S. japonicum.",2015 Aug 24,"['Wu, Chuang', 'Hou, Nan', 'Piao, Xianyu', 'Liu, Shuai', 'Cai, Pengfei', 'Xiao, Yan', 'Chen, Qijun']",Sci Rep,,,False
1d720a06cad9b69f7f45a4e7549142738114287e,PMC,Chicken egg yolk antibodies (IgY) as non-antibiotic production enhancers for use in swine production: a review,http://dx.doi.org/10.1186/s40104-015-0038-8,PMC4549021,26309735,CC BY,"In recent years, the use of in-feed antibiotics for growth and disease prevention in livestock production has been under severe scrutiny. The use and misuse of in-feed antibiotics has led to problems with drug residues in animal products and increased bacterial resistance. Chicken egg yolk antibodies (IgY) have attracted considerable attention as an alternative to antibiotics to maintain swine health and performance. Oral administration of IgY possesses many advantages over mammalian IgG such as cost-effectiveness, convenience and high yield. This review presents an overview of the potential to use IgY immunotherapy for the prevention and treatment of swine diarrhea diseases and speculates on the future of IgY technology. Included are a review of the potential applications of IgY in the control of enteric infections of either bacterial or viral origin such as enterotoxigenic Escherichia coli, Salmonella spp., rotavirus, porcine transmissible gastroenteritis virus, and porcine epidemic diarrhea virus. Some potential obstacles to the adoption of IgY technology are also discussed.",2015 Aug 25,"['Li, Xiaoyu', 'Wang, Lili', 'Zhen, Yuhong', 'Li, Shuying', 'Xu, Yongping']",J Anim Sci Biotechnol,,,True
c3b1f22e16b5f9f5961e135d3a79eaad57061aa2,PMC,Social determinants of health inequalities: towards a theoretical perspective using systems science,http://dx.doi.org/10.1186/s12939-015-0205-8,PMC4549102,26303914,CC BY,"A systems approach offers a novel conceptualization to natural and social systems. In recent years, this has led to perceiving population health outcomes as an emergent property of a dynamic and open, complex adaptive system. The current paper explores these themes further and applies the principles of systems approach and complexity science (i.e. systems science) to conceptualize social determinants of health inequalities. The conceptualization can be done in two steps: viewing health inequalities from a systems approach and extending it to include complexity science. Systems approach views health inequalities as patterns within the larger rubric of other facets of the human condition, such as educational outcomes and economic development. This anlysis requires more sophisticated models such as systems dynamic models. An extension of the approach is to view systems as complex adaptive systems, i.e. systems that are 'open' and adapt to the environment. They consist of dynamic adapting subsystems that exhibit non-linear interactions, while being 'open' to a similarly dynamic environment of interconnected systems. They exhibit emergent properties that cannot be estimated with precision by using the known interactions among its components (such as economic development, political freedom, health system, culture etc.). Different combinations of the same bundle of factors or determinants give rise to similar patterns or outcomes (i.e. property of convergence), and minor variations in the initial condition could give rise to widely divergent outcomes. Novel approaches using computer simulation models (e.g. agent-based models) would shed light on possible mechanisms as to how factors or determinants interact and lead to emergent patterns of health inequalities of populations.",2015 Aug 25,"Jayasinghe, Saroj",Int J Equity Health,,,True
d889f70c1e55668de7d33d59e76f3daf7cc8a28b,PMC,Proteomics-Based Characterization of the Humoral Immune Response in Sporotrichosis: Toward Discovery of Potential Diagnostic and Vaccine Antigens,http://dx.doi.org/10.1371/journal.pntd.0004016,PMC4549111,26305691,CC BY,"BACKGROUND: Sporothrix schenckii and associated species are agents of human and animal sporotrichosis that cause large sapronoses and zoonoses worldwide. Epidemiological surveillance has highlighted an overwhelming occurrence of the highly pathogenic fungus Sporothrix brasiliensis during feline outbreaks, leading to massive transmissions to humans. Early diagnosis of feline sporotrichosis by demonstrating the presence of a surrogate marker of infection can have a key role for selecting appropriate disease control measures and minimizing zoonotic transmission to humans. METHODOLOGY: We explored the presence and diversity of serum antibodies (IgG) specific against Sporothrix antigens in cats with sporotrichosis and evaluated the utility of these antibodies for serodiagnosis. Antigen profiling included protein extracts from the closest known relatives S. brasiliensis and S. schenckii. Enzyme-linked immunosorbent assays and immunoblotting enabled us to characterize the major antigens of feline sporotrichosis from sera from cats with sporotrichosis (n = 49), healthy cats (n = 19), and cats with other diseases (n = 20). PRINCIPAL FINDINGS: Enzyme-linked immunosorbent assay-based quantitation of anti-Sporothrix IgG exhibited high sensitivity and specificity in cats with sporotrichosis (area under the curve, 1.0; 95% confidence interval, 0.94–1; P<0.0001) versus controls. The two sets of Sporothrix antigens were remarkably cross-reactive, supporting the hypothesis that antigenic epitopes may be conserved among closely related agents. One-dimensional immunoblotting indicated that 3-carboxymuconate cyclase (a 60-kDa protein in S. brasiliensis and a 70-kDa protein in S. schenckii) is the immunodominant antigen in feline sporotrichosis. Two-dimensional immunoblotting revealed six IgG-reactive isoforms of gp60 in the S. brasiliensis proteome, similar to the humoral response found in human sporotrichosis. CONCLUSIONS: A convergent IgG-response in various hosts (mice, cats, and humans) has important implications for our understanding of the coevolution of Sporothrix and its warm-blooded hosts. We propose that 3-carboxymuconate cyclase has potential for the serological diagnosis of sporotrichosis and as target for the development of an effective multi-species vaccine against sporotrichosis in animals and humans.",2015 Aug 25,"['Rodrigues, Anderson Messias', 'Fernandes, Geisa Ferreira', 'Araujo, Leticia Mendes', 'Della Terra, Paula Portella', 'dos Santos, Priscila Oliveira', 'Pereira, Sandro Antonio', 'Schubach, Tânia Maria Pacheco', 'Burger, Eva', 'Lopes-Bezerra, Leila Maria', 'de Camargo, Zoilo Pires']",PLoS Negl Trop Dis,,,True
8afc50240bb49d3427d515da43bb2ca16975daf8,PMC,Proteomics-Based Characterization of the Humoral Immune Response in Sporotrichosis: Toward Discovery of Potential Diagnostic and Vaccine Antigens,http://dx.doi.org/10.1371/journal.pntd.0004016,PMC4549111,26305691,CC BY,"BACKGROUND: Sporothrix schenckii and associated species are agents of human and animal sporotrichosis that cause large sapronoses and zoonoses worldwide. Epidemiological surveillance has highlighted an overwhelming occurrence of the highly pathogenic fungus Sporothrix brasiliensis during feline outbreaks, leading to massive transmissions to humans. Early diagnosis of feline sporotrichosis by demonstrating the presence of a surrogate marker of infection can have a key role for selecting appropriate disease control measures and minimizing zoonotic transmission to humans. METHODOLOGY: We explored the presence and diversity of serum antibodies (IgG) specific against Sporothrix antigens in cats with sporotrichosis and evaluated the utility of these antibodies for serodiagnosis. Antigen profiling included protein extracts from the closest known relatives S. brasiliensis and S. schenckii. Enzyme-linked immunosorbent assays and immunoblotting enabled us to characterize the major antigens of feline sporotrichosis from sera from cats with sporotrichosis (n = 49), healthy cats (n = 19), and cats with other diseases (n = 20). PRINCIPAL FINDINGS: Enzyme-linked immunosorbent assay-based quantitation of anti-Sporothrix IgG exhibited high sensitivity and specificity in cats with sporotrichosis (area under the curve, 1.0; 95% confidence interval, 0.94–1; P<0.0001) versus controls. The two sets of Sporothrix antigens were remarkably cross-reactive, supporting the hypothesis that antigenic epitopes may be conserved among closely related agents. One-dimensional immunoblotting indicated that 3-carboxymuconate cyclase (a 60-kDa protein in S. brasiliensis and a 70-kDa protein in S. schenckii) is the immunodominant antigen in feline sporotrichosis. Two-dimensional immunoblotting revealed six IgG-reactive isoforms of gp60 in the S. brasiliensis proteome, similar to the humoral response found in human sporotrichosis. CONCLUSIONS: A convergent IgG-response in various hosts (mice, cats, and humans) has important implications for our understanding of the coevolution of Sporothrix and its warm-blooded hosts. We propose that 3-carboxymuconate cyclase has potential for the serological diagnosis of sporotrichosis and as target for the development of an effective multi-species vaccine against sporotrichosis in animals and humans.",2015 Aug 25,"['Rodrigues, Anderson Messias', 'Fernandes, Geisa Ferreira', 'Araujo, Leticia Mendes', 'Della Terra, Paula Portella', 'dos Santos, Priscila Oliveira', 'Pereira, Sandro Antonio', 'Schubach, Tânia Maria Pacheco', 'Burger, Eva', 'Lopes-Bezerra, Leila Maria', 'de Camargo, Zoilo Pires']",PLoS Negl Trop Dis,,,False
d38f954f1b3937ead02257e75454dd9ad2ec0ce6,PMC,"An evaluation of psychological distress and social support of survivors and contacts of Ebola virus disease infection and their relatives in Lagos, Nigeria: a cross sectional study − 2014",http://dx.doi.org/10.1186/s12889-015-2167-6,PMC4550041,26307047,CC BY,"BACKGROUND: By September 2014, an outbreak of Ebola Viral Disease (EVD) in West African countries of Guinea, Liberia, Sierra Leone, Senegal and Nigeria, had recorded over 4500 and 2200 probable or confirmed cases and deaths respectively. EVD, an emerging infectious disease, can create fear and panic among patients, contacts and relatives, which could be a risk factor for psychological distress. Psychological distress among this subgroup could have public health implication for control of EVD, because of potential effects on patient management and contact tracing. We determined the Prevalence, pattern and factors associated with psychological distress among survivors and contacts of EVD and their relatives. METHODS: In a descriptive cross sectional study, we used General Health Questionnaire to assess psychological distress and Oslo Social Support Scale to assess social support among 117 participants who survived EVD, listed as EVD contacts or their relatives at Ebola Emergency Operation Center in Lagos, Nigeria. Factors associated with psychological distress were determined using chi square/odds ratio and adjusted odds ratio. RESULTS: The mean age and standard deviation of participants was 34 +/ - 9.6 years. Of 117 participants, 78 (66.7 %) were females, 77 (65.8 %) had a tertiary education and 45 (38.5 %) were health workers. Most frequently occurring psychological distress were inability to concentrate (37.6 %) and loss of sleep over worry (33.3 %). Losing a relation to EVD outbreak (OR = 6.0, 95 % CI, 1.2–32.9) was significantly associated with feeling unhappy or depressed while being a health worker was protective (OR = 0.4, 95 % CI, 0.2–0.9). Adjusted Odds Ratio (AOR) showed losing a relation (AOR = 5.7, 95 % CI, 1.2–28.0) was a predictor of “feeling unhappy or depressed”, loss of a relation (AOR = 10.1, 95 % CI, 1.7–60.7) was a predictor of inability to concentrate. CONCLUSIONS: Survivors and contacts of EVD and their relations develop psychological distress. Development of psychological distress could be predicted by loss of family member. It is recommended that psychiatrists and other mental health specialists be part of case management teams. The clinical teams managing EVD patients should be trained on recognition of common psychological distress among patients. A mental health specialist should review contacts being monitored for EVD for psychological distress or disorders.",2015 Aug 27,"['Mohammed, Abdulaziz', 'Sheikh, Taiwo Lateef', 'Gidado, Saheed', 'Poggensee, Gabriele', 'Nguku, Patrick', 'Olayinka, Adebola', 'Ohuabunwo, Chima', 'Waziri, Ndadilnasiya', 'Shuaib, Faisal', 'Adeyemi, Joseph', 'Uzoma, Ogbonna', 'Ahmed, Abubakar', 'Doherty, Funmi', 'Nyanti, Sarah Beysolow', 'Nzuki, Charles Kyalo', 'Nasidi, Abdulsalami', 'Oyemakinde, Akin', 'Oguntimehin, Olukayode', 'Abdus-salam, Ismail Adeshina', 'Obiako, Reginald O.']",BMC Public Health,,,True
f2e06c174008ed721d0a244309601c9923548901,PMC,"Genomic analysis of codon usage shows influence of mutation pressure, natural selection, and host features on Marburg virus evolution",http://dx.doi.org/10.1186/s12862-015-0456-4,PMC4550055,26306510,CC BY,"BACKGROUND: The Marburg virus (MARV) has a negative-sense single-stranded RNA genome, belongs to the family Filoviridae, and is responsible for several outbreaks of highly fatal hemorrhagic fever. Codon usage patterns of viruses reflect a series of evolutionary changes that enable viruses to shape their survival rates and fitness toward the external environment and, most importantly, their hosts. To understand the evolution of MARV at the codon level, we report a comprehensive analysis of synonymous codon usage patterns in MARV genomes. Multiple codon analysis approaches and statistical methods were performed to determine overall codon usage patterns, biases in codon usage, and influence of various factors, including mutation pressure, natural selection, and its two hosts, Homo sapiens and Rousettus aegyptiacus. RESULTS: Nucleotide composition and relative synonymous codon usage (RSCU) analysis revealed that MARV shows mutation bias and prefers U- and A-ended codons to code amino acids. Effective number of codons analysis indicated that overall codon usage among MARV genomes is slightly biased. The Parity Rule 2 plot analysis showed that GC and AU nucleotides were not used proportionally which accounts for the presence of natural selection. Codon usage patterns of MARV were also found to be influenced by its hosts. This indicates that MARV have evolved codon usage patterns that are specific to both of its hosts. Moreover, selection pressure from R. aegyptiacus on the MARV RSCU patterns was found to be dominant compared with that from H. sapiens. Overall, mutation pressure was found to be the most important and dominant force that shapes codon usage patterns in MARV. CONCLUSIONS: To our knowledge, this is the first detailed codon usage analysis of MARV and extends our understanding of the mechanisms that contribute to codon usage and evolution of MARV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12862-015-0456-4) contains supplementary material, which is available to authorized users.",2015 Aug 26,"['Nasrullah, Izza', 'Butt, Azeem M', 'Tahir, Shifa', 'Idrees, Muhammad', 'Tong, Yigang']",BMC Evol Biol,,,True
5a89b93e5c8c6fb1352d9881f6ca6b592ef4af30,PMC,Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting,http://dx.doi.org/10.1038/srep13476,PMC4550849,26310922,CC BY,"A longstanding and still-increasing threat to the effective treatment of infectious diseases is resistance to antimicrobial countermeasures. Potentially, the targeting of host proteins and pathways essential for the detrimental effects of pathogens offers an approach that may discover broad-spectrum anti-pathogen countermeasures and circumvent the effects of pathogen mutations leading to resistance. Here we report implementation of a strategy for discovering broad-spectrum host-oriented therapies against multiple pathogenic agents by multiplex screening of drugs for protection against the detrimental effects of multiple pathogens, identification of host cell pathways inhibited by the drug, and screening for effects of the agent on other pathogens exploiting the same pathway. We show that a clinically used antimalarial drug, Amodiaquine, discovered by this strategy, protects host cells against infection by multiple toxins and viruses by inhibiting host cathepsin B. Our results reveal the practicality of discovering broadly acting anti-pathogen countermeasures that target host proteins exploited by pathogens.",2015 Aug 27,"['Zilbermintz, Leeor', 'Leonardi, William', 'Jeong, Sun-Young', 'Sjodt, Megan', 'McComb, Ryan', 'Ho, Chi-Lee C.', 'Retterer, Cary', 'Gharaibeh, Dima', 'Zamani, Rouzbeh', 'Soloveva, Veronica', 'Bavari, Sina', 'Levitin, Anastasia', 'West, Joel', 'Bradley, Kenneth A.', 'Clubb, Robert T.', 'Cohen, Stanley N.', 'Gupta, Vivek', 'Martchenko, Mikhail']",Sci Rep,,,True
0d354b208fdfa2806bf33fd03e940e057b339de5,PMC,Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting,http://dx.doi.org/10.1038/srep13476,PMC4550849,26310922,CC BY,"A longstanding and still-increasing threat to the effective treatment of infectious diseases is resistance to antimicrobial countermeasures. Potentially, the targeting of host proteins and pathways essential for the detrimental effects of pathogens offers an approach that may discover broad-spectrum anti-pathogen countermeasures and circumvent the effects of pathogen mutations leading to resistance. Here we report implementation of a strategy for discovering broad-spectrum host-oriented therapies against multiple pathogenic agents by multiplex screening of drugs for protection against the detrimental effects of multiple pathogens, identification of host cell pathways inhibited by the drug, and screening for effects of the agent on other pathogens exploiting the same pathway. We show that a clinically used antimalarial drug, Amodiaquine, discovered by this strategy, protects host cells against infection by multiple toxins and viruses by inhibiting host cathepsin B. Our results reveal the practicality of discovering broadly acting anti-pathogen countermeasures that target host proteins exploited by pathogens.",2015 Aug 27,"['Zilbermintz, Leeor', 'Leonardi, William', 'Jeong, Sun-Young', 'Sjodt, Megan', 'McComb, Ryan', 'Ho, Chi-Lee C.', 'Retterer, Cary', 'Gharaibeh, Dima', 'Zamani, Rouzbeh', 'Soloveva, Veronica', 'Bavari, Sina', 'Levitin, Anastasia', 'West, Joel', 'Bradley, Kenneth A.', 'Clubb, Robert T.', 'Cohen, Stanley N.', 'Gupta, Vivek', 'Martchenko, Mikhail']",Sci Rep,,,True
77361db3ae17729e18971ae8641a20691e44afab,PMC,Therapeutic Immunoglobulin Selected for High Antibody Titer to RSV also Contains High Antibody Titers to Other Respiratory Viruses,http://dx.doi.org/10.3389/fimmu.2015.00431,PMC4551866,26379667,CC BY,"Specific antibodies against infections most relevant to patients with primary immunodeficiency diseases are not routinely evaluated in commercial polyclonal immunoglobulin preparations. A polyclonal immunoglobulin prepared from plasma of donors having high neutralizing antibody titers to respiratory syncytial virus (RSV) was studied for the presence of antibody titers against seven additional respiratory viruses. While donors were not selected for antibody titers other than against RSV, the immunoglobulin preparation had significantly higher titers to 6 of 7 viruses compared to those present in 10 commercially available therapeutic immunoglobulin products (p ≤ 0.01 to p ≤ 0.001). To consider this as a donor-specific attribute, 20 random donor plasma samples were studied individually and identified a significant correlation between the RSV antibody titer and other respiratory virus titers: donors with high RSV titers were more likely to have higher titers to other respiratory viruses. These findings suggest either some humoral antiviral response bias or more frequent viral exposure of certain individuals.",2015 Aug 28,"['Orange, Jordan S.', 'Du, Wei', 'Falsey, Ann R.']",Front Immunol,,,True
84dfdd13ab7bf0544b5939a86b0c24b9a06e9700,PMC,The Role of Dipeptidyl Peptidase – 4 Inhibitors in Diabetic Kidney Disease,http://dx.doi.org/10.3389/fimmu.2015.00443,PMC4551869,26379674,CC BY,"Despite major advances in the understanding of the molecular mechanisms that underpin the development of diabetic kidney disease, current best practice still leaves a significant proportion of patients with end-stage kidney disease requiring renal replacement therapy. This is on a background of an increasing diabetes epidemic worldwide. Although kidney failure is a major cause of morbidity the main cause of death remains cardiovascular in nature. Hence, diabetic therapies which are both “cardio-renal” protective seem the logical way forward. In this review, we discuss the dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4inh), which are glucose-lowering agents used clinically and their role in diabetic kidney disease with specific focus on renoprotection and surrogate markers of cardiovascular disease. We highlight the novel pleiotropic effects of DPP4 that make it an attractive additional target to combat the fibrotic and inflammatory pathways in diabetic kidney disease and also discuss the current literature on the cardiovascular safety profile of DPP4inh. Clearly, these observed renoprotective effects will need to be confirmed by clinical trials to determine whether they translate into beneficial effects to patients with diabetes.",2015 Aug 28,"['Panchapakesan, Usha', 'Pollock, Carol']",Front Immunol,,,True
8a387a670706c2009e6c5e7a39c112a9e645f963,PMC,Shedding of Infectious Borna Disease Virus-1 in Living Bicolored White-Toothed Shrews,http://dx.doi.org/10.1371/journal.pone.0137018,PMC4552160,26313904,CC BY,"BACKGROUND: Many RNA viruses arise from animal reservoirs, namely bats, rodents and insectivores but mechanisms of virus maintenance and transmission still need to be addressed. The bicolored white-toothed shrew (Crocidura leucodon) has recently been identified as reservoir of the neurotropic Borna disease virus 1 (BoDV-1). PRINCIPAL FINDINGS: Six out of eleven wild living bicoloured white-toothed shrews were trapped and revealed to be naturally infected with BoDV-1. All shrews were monitored in captivity in a long-term study over a time period up to 600 days that differed between the individual shrews. Interestingly, all six animals showed an asymptomatic course of infection despite virus shedding via various routes indicating a highly adapted host-pathogen interaction. Infectious virus and viral RNA were demonstrated in saliva, urine, skin swabs, lacrimal fluid and faeces, both during the first 8 weeks of the investigation period and for long time shedding after more than 250 days in captivity. CONCLUSIONS: The various ways of shedding ensure successful virus maintenance in the reservoir population but also transmission to accidental hosts such as horses and sheep. Naturally BoDV-1-infected living shrews serve as excellent tool to unravel host and pathogen factors responsible for persistent viral co-existence in reservoir species while maintaining their physiological integrity despite high viral load in many organ systems.",2015 Aug 27,"['Nobach, Daniel', 'Bourg, Manon', 'Herzog, Sibylle', 'Lange-Herbst, Hildburg', 'Encarnação, Jorge A.', 'Eickmann, Markus', 'Herden, Christiane']",PLoS One,,,True
01cad955f2c6d1373797935f0b33b23d386b26bf,PMC,Shedding of Infectious Borna Disease Virus-1 in Living Bicolored White-Toothed Shrews,http://dx.doi.org/10.1371/journal.pone.0137018,PMC4552160,26313904,CC BY,"BACKGROUND: Many RNA viruses arise from animal reservoirs, namely bats, rodents and insectivores but mechanisms of virus maintenance and transmission still need to be addressed. The bicolored white-toothed shrew (Crocidura leucodon) has recently been identified as reservoir of the neurotropic Borna disease virus 1 (BoDV-1). PRINCIPAL FINDINGS: Six out of eleven wild living bicoloured white-toothed shrews were trapped and revealed to be naturally infected with BoDV-1. All shrews were monitored in captivity in a long-term study over a time period up to 600 days that differed between the individual shrews. Interestingly, all six animals showed an asymptomatic course of infection despite virus shedding via various routes indicating a highly adapted host-pathogen interaction. Infectious virus and viral RNA were demonstrated in saliva, urine, skin swabs, lacrimal fluid and faeces, both during the first 8 weeks of the investigation period and for long time shedding after more than 250 days in captivity. CONCLUSIONS: The various ways of shedding ensure successful virus maintenance in the reservoir population but also transmission to accidental hosts such as horses and sheep. Naturally BoDV-1-infected living shrews serve as excellent tool to unravel host and pathogen factors responsible for persistent viral co-existence in reservoir species while maintaining their physiological integrity despite high viral load in many organ systems.",2015 Aug 27,"['Nobach, Daniel', 'Bourg, Manon', 'Herzog, Sibylle', 'Lange-Herbst, Hildburg', 'Encarnação, Jorge A.', 'Eickmann, Markus', 'Herden, Christiane']",PLoS One,,,False
dec1d801c2d5a971207df424ede4b1d65267b212,PMC,Transcriptional slippage in the positive-sense RNA virus family Potyviridae,http://dx.doi.org/10.15252/embr.201540509,PMC4552492,26113364,CC BY,"The family Potyviridae encompasses ∼30% of plant viruses and is responsible for significant economic losses worldwide. Recently, a small overlapping coding sequence, termed pipo, was found to be conserved in the genomes of all potyvirids. PIPO is expressed as part of a frameshift protein, P3N-PIPO, which is essential for virus cell-to-cell movement. However, the frameshift expression mechanism has hitherto remained unknown. Here, we demonstrate that transcriptional slippage, specific to the viral RNA polymerase, results in a population of transcripts with an additional “A” inserted within a highly conserved GAAAAAA sequence, thus enabling expression of P3N-PIPO. The slippage efficiency is ∼2% in Turnip mosaic virus and slippage is inhibited by mutations in the GAAAAAA sequence. While utilization of transcriptional slippage is well known in negative-sense RNA viruses such as Ebola, mumps and measles, to our knowledge this is the first report of its widespread utilization for gene expression in positive-sense RNA viruses.",2015 Aug 25,"['Olspert, Allan', 'Chung, Betty Y-W', 'Atkins, John F', 'Carr, John P', 'Firth, Andrew E']",EMBO Rep,,,True
8ec5d7c229660267edbf9932e5ebe5edf0cea6fc,PMC,Transcriptional slippage in the positive-sense RNA virus family Potyviridae,http://dx.doi.org/10.15252/embr.201540509,PMC4552492,26113364,CC BY,"The family Potyviridae encompasses ∼30% of plant viruses and is responsible for significant economic losses worldwide. Recently, a small overlapping coding sequence, termed pipo, was found to be conserved in the genomes of all potyvirids. PIPO is expressed as part of a frameshift protein, P3N-PIPO, which is essential for virus cell-to-cell movement. However, the frameshift expression mechanism has hitherto remained unknown. Here, we demonstrate that transcriptional slippage, specific to the viral RNA polymerase, results in a population of transcripts with an additional “A” inserted within a highly conserved GAAAAAA sequence, thus enabling expression of P3N-PIPO. The slippage efficiency is ∼2% in Turnip mosaic virus and slippage is inhibited by mutations in the GAAAAAA sequence. While utilization of transcriptional slippage is well known in negative-sense RNA viruses such as Ebola, mumps and measles, to our knowledge this is the first report of its widespread utilization for gene expression in positive-sense RNA viruses.",2015 Aug 25,"['Olspert, Allan', 'Chung, Betty Y-W', 'Atkins, John F', 'Carr, John P', 'Firth, Andrew E']",EMBO Rep,,,False
f19eac518ac044aff2085587409e8b6d2a02aa99,PMC,Transcriptional slippage in the positive-sense RNA virus family Potyviridae,http://dx.doi.org/10.15252/embr.201540509,PMC4552492,26113364,CC BY,"The family Potyviridae encompasses ∼30% of plant viruses and is responsible for significant economic losses worldwide. Recently, a small overlapping coding sequence, termed pipo, was found to be conserved in the genomes of all potyvirids. PIPO is expressed as part of a frameshift protein, P3N-PIPO, which is essential for virus cell-to-cell movement. However, the frameshift expression mechanism has hitherto remained unknown. Here, we demonstrate that transcriptional slippage, specific to the viral RNA polymerase, results in a population of transcripts with an additional “A” inserted within a highly conserved GAAAAAA sequence, thus enabling expression of P3N-PIPO. The slippage efficiency is ∼2% in Turnip mosaic virus and slippage is inhibited by mutations in the GAAAAAA sequence. While utilization of transcriptional slippage is well known in negative-sense RNA viruses such as Ebola, mumps and measles, to our knowledge this is the first report of its widespread utilization for gene expression in positive-sense RNA viruses.",2015 Aug 25,"['Olspert, Allan', 'Chung, Betty Y-W', 'Atkins, John F', 'Carr, John P', 'Firth, Andrew E']",EMBO Rep,,,False
7266d5a2b588f4bd08e301590247156d59a7f227,PMC,A Rapid Method to Characterize Mouse IgG Antibodies and Isolate Native Antigen Binding IgG B Cell Hybridomas,http://dx.doi.org/10.1371/journal.pone.0136613,PMC4552657,26317987,CC BY,"B cell hybridomas are an important source of monoclonal antibodies. In this paper, we developed a high-throughput method to characterize mouse IgG antibodies using surface plasmon resonance technology. This assay rapidly determines their sub-isotypes, whether they bind native antigen and their approximate affinities for the antigen using only 50 μl of hybridoma cell culture supernatant. Moreover, we found that mouse hybridomas secreting IgG antibodies also have membrane form IgG expression without Igα. Based on this surface IgG, we used flow cytometry to isolate rare γ2a isotype switched variants from a γ2b antibody secreting hybridoma cell line. Also, we used fluorescent antigen to single cell sort antigen binding hybridoma cells from bulk mixture of fused hybridoma cells instead of the traditional multi-microwell plate screening and limiting dilution sub-cloning thus saving time and labor. The IgG monoclonal antibodies specific for the native antigen identified with these methods are suitable for in vivo therapeutic uses, but also for sandwich ELISA assays, histology, flow cytometry, immune precipitation and x-ray crystallography.",2015 Aug 28,"['Liu, Haolin', 'White, Janice', 'Crawford, Frances', 'Jin, Niyun', 'Ju, Xiangwu', 'Liu, Kangtai', 'Jiang, Chengyu', 'Marrack, Philippa', 'Zhang, Gongyi', 'Kappler, John W.']",PLoS One,,,True
92f4de5e3cd8e63cd679d4af3db2d4d44e929ecd,PMC,Serotype 1 and 8 Pneumococci Evade Sensing by Inflammasomes in Human Lung Tissue,http://dx.doi.org/10.1371/journal.pone.0137108,PMC4552725,26317436,CC BY,"Streptococcus pneumoniae is a major cause of pneumonia, sepsis and meningitis. The pore-forming toxin pneumolysin is a key virulence factor of S. pneumoniae, which can be sensed by the NLRP3 inflammasome. Among the over 90 serotypes, serotype 1 pneumococci (particularly MLST306) have emerged across the globe as a major cause of invasive disease. The cause for its particularity is, however, incompletely understood. We therefore examined pneumococcal infection in human cells and a human lung organ culture system mimicking infection of the lower respiratory tract. We demonstrate that different pneumococcal serotypes differentially activate inflammasome-dependent IL-1β production in human lung tissue and cells. Whereas serotype 2, 3, 6B, 9N pneumococci expressing fully haemolytic pneumolysins activate NLRP3 inflammasome-dependent responses, serotype 1 and 8 strains expressing non-haemolytic toxins are poor activators of IL-1β production. Accordingly, purified haemolytic pneumolysin but not serotype 1-associated non-haemolytic toxin activates strong IL-1β production in human lungs. Our data suggest that the evasion of inflammasome-dependent innate immune responses by serotype 1 pneumococci might contribute to their ability to cause invasive diseases in humans.",2015 Aug 28,"['Fatykhova, Diana', 'Rabes, Anne', 'Machnik, Christoph', 'Guruprasad, Kunchur', 'Pache, Florence', 'Berg, Johanna', 'Toennies, Mario', 'Bauer, Torsten T.', 'Schneider, Paul', 'Schimek, Maria', 'Eggeling, Stephan', 'Mitchell, Timothy J.', 'Mitchell, Andrea M.', 'Hilker, Rolf', 'Hain, Torsten', 'Suttorp, Norbert', 'Hippenstiel, Stefan', 'Hocke, Andreas C.', 'Opitz, Bastian']",PLoS One,,,True
7432dbac9b72daf18b639ba85a59b2e676b6b09c,PMC,Different Blood Cell-Derived Transcriptome Signatures in Cows Exposed to Vaccination Pre- or Postpartum,http://dx.doi.org/10.1371/journal.pone.0136927,PMC4552870,26317664,CC BY,"Periparturient cows have been found to reveal immunosuppression, frequently associated with increased susceptibility to uterine and mammary infections. To improve understanding of the causes and molecular regulatory mechanisms accounting for this phenomenon around calving, we examined the effect of an antigen challenge on gene expression modulation on cows prior to (BC) or after calving (AC) using whole transcriptome sequencing (RNAseq). The transcriptome analysis of the cows’ blood identified a substantially higher number of loci affected in BC cows (2,235) in response to vaccination compared to AC cows (208) and revealed a divergent transcriptional profile specific for each group. In BC cows, a variety of loci involved in immune defense and cellular signaling processes were transcriptionally activated, whereas protein biosynthesis and posttranslational processes were tremendously impaired in response to vaccination. Furthermore, energy metabolism in the blood cells of BC cows was shifted from oxidative phosphorylation to the glycolytic system. In AC cows, the number and variety of regulated pathways involved in immunomodulation and maintenance of immnunocompetence are considerably lower after vaccination, and upregulation of arginine degradation was suggested as an immunosuppressive mechanism. Elevated transcript levels of erythrocyte-specific genes involved in gas exchange processes were a specific transcriptional signature in AC cows pointing to hematopoiesis activation. The divergent and substantially lower magnitude of transcriptional modulation in response to vaccination in AC cows provides evidence for a suppressed immune capacity of early lactating cows on the molecular level and demonstrates that an efficient immune response of cows is related to their physiological and metabolic status.",2015 Aug 28,"['Weikard, Rosemarie', 'Demasius, Wiebke', 'Hadlich, Frieder', 'Kühn, Christa']",PLoS One,,,True
8147b5b09a09887d1b4c4871d9d49746d8c4d418,PMC,A Multiple Antigenic Peptide Mimicking Peptidoglycan Induced T Cell Responses to Protect Mice from Systemic Infection with Staphylococcus aureus,http://dx.doi.org/10.1371/journal.pone.0136888,PMC4552945,26317210,CC BY,"Due to the enormous capacity of Staphylococcus aureus to acquire antibiotic resistance, it becomes imperative to develop vaccines for decreasing the risk of its life-threatening infections. Peptidoglycan (PGN) is a conserved and major component of S. aureus cell wall. However, it has not been used as a vaccine candidate since it is a thymus-independent antigen. In this study, we synthesized a multiple antigenic peptide, named MAP27, which comprised four copies of a peptide that mimics the epitope of PGN. After immunization with MAP27 five times and boosting with heat-inactivated bacterium one time, anti-MAP27 serum bound directly to S. aureus or PGN. Immunization with MAP27 decreased the bacterial burden in organs of BALB/c mice and significantly prolonged their survival time after S. aureus lethal-challenge. The percentage of IFN-γ(+)CD3(+) T cells and IL-17(+)CD4(+) T cells in spleen, as well as the levels of IFN-γ, IL-17A/F and CCL3 in spleen and lung, significantly increased in the MAP27-immunized mice after infection. Moreover, in vitro incubation of heat-inactivated S. aureus with splenocytes isolated from MAP27-immunized mice stimulated the production of IFN-γ and IL-17A/F. Our findings demonstrated that MAP27, as a thymus-dependent antigen, is efficient at eliciting T cell-mediated responses to protect mice from S. aureus infection. This study sheds light on a possible strategy to design vaccines against S. aureus.",2015 Aug 28,"['Wang, Xiang-Yu', 'Huang, Zhao-Xia', 'Chen, Yi-Guo', 'Lu, Xiao', 'Zhu, Ping', 'Wen, Kun', 'Fu, Ning', 'Liu, Bei-Yi']",PLoS One,,,True
e4065a39d9df47f5987404da83abbf7a10fa57db,PMC,Inhibitory effects of magnolol and honokiol on human calcitonin aggregation,http://dx.doi.org/10.1038/srep13556,PMC4555095,26324190,CC BY,"Amyloid formation is associated with multiple amyloidosis diseases. Human calcitonin (hCT) is a typical amyloidogenic peptide, its aggregation is associated with medullary carcinoma of the thyroid (MTC), and also limits its clinical application. Magnolia officinalis is a traditional Chinese herbal medicine; its two major polyphenol components, magnolol (Mag) and honokiol (Hon), have displayed multiple functions. Polyphenols like flavonoids and their derivatives have been extensively studied as amyloid inhibitors. However, the anti-amyloidogenic property of a biphenyl backbone containing polyphenols such as Mag and Hon has not been reported. In this study, these two compounds were tested for their effects on hCT aggregation. We found that Mag and Hon both inhibited the amyloid formation of hCT, whereas Mag showed a stronger inhibitory effect; moreover, they both dose-dependently disassembled preformed hCT aggregates. Further immuno-dot blot and dynamic light scattering studies suggested Mag and Hon suppressed the aggregation of hCT both at the oligomerization and the fibrillation stages, while MTT-based and dye-leakage assays demonstrated that Mag and Hon effectively reduced cytotoxicity caused by hCT aggregates. Furthermore, isothermal titration calorimetry indicated Mag and Hon both interact with hCT. Together, our study suggested a potential anti-amyloidogenic property of these two compounds and their structure related derivatives.",2015 Sep 1,"['Guo, Caiao', 'Ma, Liang', 'Zhao, Yudan', 'Peng, Anlin', 'Cheng, Biao', 'Zhou, Qiaoqiao', 'Zheng, Ling', 'Huang, Kun']",Sci Rep,,,True
e62bebc2ecb5a648b06eb708f88a8024231a474d,PMC,Cullin4 Is Pro-Viral during West Nile Virus Infection of Culex Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1005143,PMC4556628,26325027,CC BY,"Although mosquitoes serve as vectors of many pathogens of public health importance, their response to viral infection is poorly understood. It also remains to be investigated whether viruses deploy some mechanism to be able to overcome this immune response. Here, we have used an RNA-Seq approach to identify differentially regulated genes in Culex quinquefasciatus cells following West Nile virus (WNV) infection, identifying 265 transcripts from various cellular pathways that were either upregulated or downregulated. Ubiquitin-proteasomal pathway genes, comprising 12% of total differentially regulated genes, were selected for further validation by real time RT-qPCR and functional analysis. It was found that treatment of infected cells with proteasomal inhibitor, MG-132, decreased WNV titers, indicating importance of this pathway during infection process. In infection models, the Culex ortholog of mammalian Cul4A/B (cullin RING ubiquitin ligase) was found to be upregulated in vitro as well as in vivo, especially in midguts of mosquitoes. Gene knockdown using dsRNA and overexpression studies indicated that Culex Cul4 acts as a pro-viral protein by degradation of CxSTAT via ubiquitin-proteasomal pathway. We also show that gene knockdown of Culex Cul4 leads to activation of the Jak-STAT pathway in mosquitoes leading to decrease viral replication in the body as well as saliva. Our results suggest a novel mechanism adopted by WNV to overcome mosquito immune response and increase viral replication.",2015 Sep 1,"['Paradkar, Prasad N.', 'Duchemin, Jean-Bernard', 'Rodriguez-Andres, Julio', 'Trinidad, Lee', 'Walker, Peter J.']",PLoS Pathog,,,True
a087143ccafb8699cca687a6548e99633a98fe21,PMC,Blocking the PI3K/AKT pathway enhances mammalian reovirus replication by repressing IFN-stimulated genes,http://dx.doi.org/10.3389/fmicb.2015.00886,PMC4557281,26388843,CC BY,"Many host cellular signaling pathways were activated and exploited by virus infection for more efficient replication. The PI3K/Akt pathway has recently attracted considerable interest due to its role in regulating virus replication. This study demonstrated for the first time that the mammalian reovirus strains Masked Palm Civet/China/2004 (MPC/04) and Bat/China/2003 (B/03) can induce transient activation of the PI3K/Akt pathway early in infection in vitro. When UV-treated, both viruses activated PI3K/Akt signaling, indicating that the virus/receptor interaction was sufficient to activate PI3K/Akt. Reovirus virions can use both clathrin- and caveolae-mediated endocytosis, but only chlorpromazine, a specific inhibitor of clathrin-mediated endocytosis, or siRNA targeting clathrin suppressed Akt phosphorylation. We also identified the upstream molecules of the PI3K pathway. Virus infection induced phosphorylation of focal adhesion kinase (FAK) but not Gab1, and blockage of FAK phosphorylation suppressed Akt phosphorylation. Blockage of PI3K/Akt activation increased virus RNA synthesis and viral yield. We also found that reovirus infection activated the IFN-stimulated response element (ISRE) in an interferon-independent manner and up-regulated IFN-stimulated genes (ISGs) via the PI3K/Akt/EMSY pathway. Suppression of PI3K/Akt activation impaired the induction of ISRE and down-regulated the expression of ISGs. Overexpression of ISG15 and Viperin inhibited virus replication, and knockdown of either enhanced virus replication. Collectively, these results demonstrate that PI3K/Akt activated by mammalian reovirus serves as a pathway for sensing and then inhibiting virus replication/infection.",2015 Sep 2,"['Tian, Jin', 'Zhang, Xiaozhan', 'Wu, Hongxia', 'Liu, Chunguo', 'Li, Zhijie', 'Hu, Xiaoliang', 'Su, Shuo', 'Wang, Lin-Fa', 'Qu, Liandong']",Front Microbiol,,,True
e26f7a365e99b48b99e89e3f3ffcef15e6285475,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
2adb9aba7e55520011c66eea76f9b2e2e60ac108,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
da40d98e7c370e331d46f01d43d2341fd522ceef,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
fe2a2777754e368c16905eafd9c601e1d1738485,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
de664fabc611f10d71ba84039bc6784bdcf118d8,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
ca453f509ed7728ef7387c766151fbe8ed846aec,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
4e2a01fa896636962bb7924ec0c0e8b41fde379e,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
2672bf33e834b4479c328051e1bbbdcd94124587,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
7ea553f62384642e5089af579984416d77073dfe,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
75964abb7d9b187aab3a205e851fa6c646e9f96b,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,True
c4b02808f112f00b4271fcd1eabdba3b7edcc1a3,PMC,"Preparedness of Hospitals in the Republic of Ireland for an Influenza Pandemic, an Infection Control Perspective",http://dx.doi.org/10.1186/s12889-015-2025-6,PMC4557843,26335570,CC BY,"BACKGROUND: When an influenza pandemic occurs most of the population is susceptible and attack rates can range as high as 40–50 %. The most important failure in pandemic planning is the lack of standards or guidelines regarding what it means to be ‘prepared’. The aim of this study was to assess the preparedness of acute hospitals in the Republic of Ireland for an influenza pandemic from an infection control perspective. METHODS: This was a cross sectional study involving a questionnaire completed by infection control nurses, time period from June – July 2013, (3 weeks) from acute public and private hospitals in the Republic of Ireland. A total of 46 out of 56 hospitals responded to the questionnaire. RESULTS: From a sample of 46 Irish hospitals, it was found that Irish hospitals are not fully prepared for an influenza pandemic despite the 2009 Influenza A (H1N1) pandemic. In 2013, thirty five per cent of Irish hospitals have participated in an emergency plan or infectious disease exercise and have plans or been involved in local planning efforts to care for patients at non-health care facilities. Sixty per cent of Irish hospitals did not compile or did not know if the hospital had compiled a “lessons learned” from any exercise that were then used to revise emergency response plans. Fifty two per cent of hospitals have sufficient airborne isolation capacity to address routine needs and have an interim emergency plan to address needs during an outbreak. Fifty one percent of hospitals have taken specific measures to stockpile or have reserve medical supplies e.g. masks, ventilators and linen. CONCLUSIONS: This is the first study carried out in the Republic of Ireland investigating the current preparedness for an influenza pandemic from an infection control perspective. Deficits exist in the provision of emergency planning committees, testing of emergency plans, airborne isolation facilities, stockpiling of personal protective equipment (PPE) and medical supplies and organisational schemes/incentives for healthcare workers to continue to work in a pandemic. While Irish standards are comparable to findings from international studies, the health care service needs to continue to enhance preparedness for an influenza pandemic and implement standard preparedness guidance for all Irish hospitals.",2015 Sep 3,"['Reidy, Mary', 'Ryan, Fiona', 'Hogan, Dervla', 'Lacey, Sean', 'Buckley, Claire']",BMC Public Health,,,True
6cad43bc914661354dc70f971c5517021eb3a823,PMC,Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections,http://dx.doi.org/10.1371/journal.pone.0136526,PMC4558027,26332375,CC BY,"BACKGROUND: Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. METHODS: A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. RESULTS: A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). CONCLUSION: The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis.",2015 Sep 2,"['Cebey-López, Miriam', 'Herberg, Jethro', 'Pardo-Seco, Jacobo', 'Gómez-Carballa, Alberto', 'Martinón-Torres, Nazareth', 'Salas, Antonio', 'Martinón-Sánchez, José María', 'Gormley, Stuart', 'Sumner, Edward', 'Fink, Colin', 'Martinón-Torres, Federico', None]",PLoS One,,,True
208f4d527c8ac85c04dd9e431babfaaa54e66428,PMC,One Health – a strategy for resilience in a changing arctic,http://dx.doi.org/10.3402/ijch.v74.27913,PMC4558275,26333722,CC BY,"The circumpolar north is uniquely vulnerable to the health impacts of climate change. While international Arctic collaboration on health has enhanced partnerships and advanced the health of inhabitants, significant challenges lie ahead. One Health is an approach that considers the connections between the environment, plant, animal and human health. Understanding this is increasingly critical in assessing the impact of global climate change on the health of Arctic inhabitants. The effects of climate change are complex and difficult to predict with certainty. Health risks include changes in the distribution of infectious disease, expansion of zoonotic diseases and vectors, changing migration patterns, impacts on food security and changes in water availability and quality, among others. A regional network of diverse stakeholder and transdisciplinary specialists from circumpolar nations and Indigenous groups can advance the understanding of complex climate-driven health risks and provide community-based strategies for early identification, prevention and adaption of health risks in human, animals and environment. We propose a regional One Health approach for assessing interactions at the Arctic human–animal–environment interface to enhance the understanding of, and response to, the complexities of climate change on the health of the Arctic inhabitants.",2015 Sep 1,"['Ruscio, Bruce A.', 'Brubaker, Michael', 'Glasser, Joshua', 'Hueston, Will', 'Hennessy, Thomas W.']",Int J Circumpolar Health,,,True
09e8d6985e74029c794e543bde68fba0d07133a4,PMC,"Middle East respiratory syndrome coronavirus: transmission, virology and therapeutic targeting to aid in outbreak control",http://dx.doi.org/10.1038/emm.2015.76,PMC4558490,26315600,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes high fever, cough, acute respiratory tract infection and multiorgan dysfunction that may eventually lead to the death of the infected individuals. MERS-CoV is thought to be transmitted to humans through dromedary camels. The occurrence of the virus was first reported in the Middle East and it subsequently spread to several parts of the world. Since 2012, about 1368 infections, including ~487 deaths, have been reported worldwide. Notably, the recent human-to-human ‘superspreading' of MERS-CoV in hospitals in South Korea has raised a major global health concern. The fatality rate in MERS-CoV infection is four times higher compared with that of the closely related severe acute respiratory syndrome coronavirus infection. Currently, no drug has been clinically approved to control MERS-CoV infection. In this study, we highlight the potential drug targets that can be used to develop anti-MERS-CoV therapeutics.",2015 Aug 28,"['Durai, Prasannavenkatesh', 'Batool, Maria', 'Shah, Masaud', 'Choi, Sangdun']",Exp Mol Med,,,True
6695b6ccee47ef931d9a91dd8986a612ec626ea2,PMC,Transmission characteristics of MERS and SARS in the healthcare setting: a comparative study,http://dx.doi.org/10.1186/s12916-015-0450-0,PMC4558759,26336062,CC BY,"BACKGROUND: The Middle East respiratory syndrome (MERS) coronavirus has caused recurrent outbreaks in the Arabian Peninsula since 2012. Although MERS has low overall human-to-human transmission potential, there is occasional amplification in the healthcare setting, a pattern reminiscent of the dynamics of the severe acute respiratory syndrome (SARS) outbreaks in 2003. Here we provide a head-to-head comparison of exposure patterns and transmission dynamics of large hospital clusters of MERS and SARS, including the most recent South Korean outbreak of MERS in 2015. METHODS: To assess the unexpected nature of the recent South Korean nosocomial outbreak of MERS and estimate the probability of future large hospital clusters, we compared exposure and transmission patterns for previously reported hospital clusters of MERS and SARS, based on individual-level data and transmission tree information. We carried out simulations of nosocomial outbreaks of MERS and SARS using branching process models rooted in transmission tree data, and inferred the probability and characteristics of large outbreaks. RESULTS: A significant fraction of MERS cases were linked to the healthcare setting, ranging from 43.5 % for the nosocomial outbreak in Jeddah, Saudi Arabia, in 2014 to 100 % for both the outbreak in Al-Hasa, Saudi Arabia, in 2013 and the outbreak in South Korea in 2015. Both MERS and SARS nosocomial outbreaks are characterized by early nosocomial super-spreading events, with the reproduction number dropping below 1 within three to five disease generations. There was a systematic difference in the exposure patterns of MERS and SARS: a majority of MERS cases occurred among patients who sought care in the same facilities as the index case, whereas there was a greater concentration of SARS cases among healthcare workers throughout the outbreak. Exposure patterns differed slightly by disease generation, however, especially for SARS. Moreover, the distributions of secondary cases per single primary case varied highly across individual hospital outbreaks (Kruskal–Wallis test; P < 0.0001), with significantly higher transmission heterogeneity in the distribution of secondary cases for MERS than SARS. Simulations indicate a 2-fold higher probability of occurrence of large outbreaks (>100 cases) for SARS than MERS (2 % versus 1 %); however, owing to higher transmission heterogeneity, the largest outbreaks of MERS are characterized by sharper incidence peaks. The probability of occurrence of MERS outbreaks larger than the South Korean cluster (n = 186) is of the order of 1 %. CONCLUSIONS: Our study suggests that the South Korean outbreak followed a similar progression to previously described hospital clusters involving coronaviruses, with early super-spreading events generating a disproportionately large number of secondary infections, and the transmission potential diminishing greatly in subsequent generations. Differences in relative exposure patterns and transmission heterogeneity of MERS and SARS could point to changes in hospital practices since 2003 or differences in transmission mechanisms of these coronaviruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0450-0) contains supplementary material, which is available to authorized users.",2015 Sep 3,"['Chowell, Gerardo', 'Abdirizak, Fatima', 'Lee, Sunmi', 'Lee, Jonggul', 'Jung, Eunok', 'Nishiura, Hiroshi', 'Viboud, Cécile']",BMC Med,,,False
30b285a628c951e7c2d73848be13204f59b2fa73,PMC,Transmission characteristics of MERS and SARS in the healthcare setting: a comparative study,http://dx.doi.org/10.1186/s12916-015-0450-0,PMC4558759,26336062,CC BY,"BACKGROUND: The Middle East respiratory syndrome (MERS) coronavirus has caused recurrent outbreaks in the Arabian Peninsula since 2012. Although MERS has low overall human-to-human transmission potential, there is occasional amplification in the healthcare setting, a pattern reminiscent of the dynamics of the severe acute respiratory syndrome (SARS) outbreaks in 2003. Here we provide a head-to-head comparison of exposure patterns and transmission dynamics of large hospital clusters of MERS and SARS, including the most recent South Korean outbreak of MERS in 2015. METHODS: To assess the unexpected nature of the recent South Korean nosocomial outbreak of MERS and estimate the probability of future large hospital clusters, we compared exposure and transmission patterns for previously reported hospital clusters of MERS and SARS, based on individual-level data and transmission tree information. We carried out simulations of nosocomial outbreaks of MERS and SARS using branching process models rooted in transmission tree data, and inferred the probability and characteristics of large outbreaks. RESULTS: A significant fraction of MERS cases were linked to the healthcare setting, ranging from 43.5 % for the nosocomial outbreak in Jeddah, Saudi Arabia, in 2014 to 100 % for both the outbreak in Al-Hasa, Saudi Arabia, in 2013 and the outbreak in South Korea in 2015. Both MERS and SARS nosocomial outbreaks are characterized by early nosocomial super-spreading events, with the reproduction number dropping below 1 within three to five disease generations. There was a systematic difference in the exposure patterns of MERS and SARS: a majority of MERS cases occurred among patients who sought care in the same facilities as the index case, whereas there was a greater concentration of SARS cases among healthcare workers throughout the outbreak. Exposure patterns differed slightly by disease generation, however, especially for SARS. Moreover, the distributions of secondary cases per single primary case varied highly across individual hospital outbreaks (Kruskal–Wallis test; P < 0.0001), with significantly higher transmission heterogeneity in the distribution of secondary cases for MERS than SARS. Simulations indicate a 2-fold higher probability of occurrence of large outbreaks (>100 cases) for SARS than MERS (2 % versus 1 %); however, owing to higher transmission heterogeneity, the largest outbreaks of MERS are characterized by sharper incidence peaks. The probability of occurrence of MERS outbreaks larger than the South Korean cluster (n = 186) is of the order of 1 %. CONCLUSIONS: Our study suggests that the South Korean outbreak followed a similar progression to previously described hospital clusters involving coronaviruses, with early super-spreading events generating a disproportionately large number of secondary infections, and the transmission potential diminishing greatly in subsequent generations. Differences in relative exposure patterns and transmission heterogeneity of MERS and SARS could point to changes in hospital practices since 2003 or differences in transmission mechanisms of these coronaviruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0450-0) contains supplementary material, which is available to authorized users.",2015 Sep 3,"['Chowell, Gerardo', 'Abdirizak, Fatima', 'Lee, Sunmi', 'Lee, Jonggul', 'Jung, Eunok', 'Nishiura, Hiroshi', 'Viboud, Cécile']",BMC Med,,,True
cd9086c9edba2e717fab23027e7debb9c21c23e4,PMC,Complete Genome Sequence of Porcine Deltacoronavirus Strain CH/Sichuan/S27/2012 from Mainland China,http://dx.doi.org/10.1128/genomeA.00945-15,PMC4559728,26337879,CC BY,We report the first complete genome sequence of porcine deltacoronavirus (PDCoV) strain CH/Sichuan/S27/2012 identified in feces of diarrheic piglets from mainland China in 2012. This strain has two unique in-frame deletions within the ORF1a gene and is phylogenetically between the prototype PDCoV (HKU15) and the 2014 U.S. strains.,2015 Sep 3,"['Wang, Yi-Wen', 'Yue, Hua', 'Fang, Weihuan', 'Huang, Yao-Wei']",Genome Announc,,,True
880359b9dd6158ec31280e45a077f9d59b68e22f,PMC,"Whole-genome Sequencing for Tracing the Transmission Link between Two ARD Outbreaks Caused by a Novel HAdV Serotype 7 Variant, China",http://dx.doi.org/10.1038/srep13617,PMC4559894,26338697,CC BY,"From December 2012 to February 2013, two outbreaks of acute respiratory disease caused by HAdV-7 were reported in China. We investigated possible transmission links between these two seemingly unrelated outbreaks by integration of epidemiological and whole-genome sequencing (WGS) data. WGS analyses showed that the HAdV-7 isolates from the two outbreaks were genetically indistinguishable; however, a 12 bp deletion in the virus-associated RNA gene distinguished the outbreak isolates from other HAdV-7 isolates. Outbreak HAdV-7 isolates demonstrated increased viral replication compared to non-outbreak associated HAdV-7 isolate. Epidemiological data supported that the first outbreak was caused by introduction of the novel HAdV-7 virus by an infected recruit upon arrival at the training base. Nosocomial transmission by close contacts was the most likely source leading to onset of the second HAdV-7 outbreak, establishing the apparent transmission link between the outbreaks. Our findings imply that in-hospital contact investigations should be encouraged to reduce or interrupt further spread of infectious agents when treating outbreak cases, and WGS can provide useful information guiding infection-control interventions.",2015 Sep 4,"['Qiu, Shaofu', 'Li, Peng', 'Liu, Hongbo', 'Wang, Yong', 'Liu, Nan', 'Li, Chengyi', 'Li, Shenlong', 'Li, Ming', 'Jiang, Zhengjie', 'Sun, Huandong', 'Li, Ying', 'Xie, Jing', 'Yang, Chaojie', 'Wang, Jian', 'Li, Hao', 'Yi, Shengjie', 'Wu, Zhihao', 'Jia, Leili', 'Wang, Ligui', 'Hao, Rongzhang', 'Sun, Yansong', 'Huang, Liuyu', 'Ma, Hui', 'Yuan, Zhengquan', 'Song, Hongbin']",Sci Rep,,,True
411bf0a46d2b3dcaba0c11447380a476deb6d111,PMC,"Whole-genome Sequencing for Tracing the Transmission Link between Two ARD Outbreaks Caused by a Novel HAdV Serotype 7 Variant, China",http://dx.doi.org/10.1038/srep13617,PMC4559894,26338697,CC BY,"From December 2012 to February 2013, two outbreaks of acute respiratory disease caused by HAdV-7 were reported in China. We investigated possible transmission links between these two seemingly unrelated outbreaks by integration of epidemiological and whole-genome sequencing (WGS) data. WGS analyses showed that the HAdV-7 isolates from the two outbreaks were genetically indistinguishable; however, a 12 bp deletion in the virus-associated RNA gene distinguished the outbreak isolates from other HAdV-7 isolates. Outbreak HAdV-7 isolates demonstrated increased viral replication compared to non-outbreak associated HAdV-7 isolate. Epidemiological data supported that the first outbreak was caused by introduction of the novel HAdV-7 virus by an infected recruit upon arrival at the training base. Nosocomial transmission by close contacts was the most likely source leading to onset of the second HAdV-7 outbreak, establishing the apparent transmission link between the outbreaks. Our findings imply that in-hospital contact investigations should be encouraged to reduce or interrupt further spread of infectious agents when treating outbreak cases, and WGS can provide useful information guiding infection-control interventions.",2015 Sep 4,"['Qiu, Shaofu', 'Li, Peng', 'Liu, Hongbo', 'Wang, Yong', 'Liu, Nan', 'Li, Chengyi', 'Li, Shenlong', 'Li, Ming', 'Jiang, Zhengjie', 'Sun, Huandong', 'Li, Ying', 'Xie, Jing', 'Yang, Chaojie', 'Wang, Jian', 'Li, Hao', 'Yi, Shengjie', 'Wu, Zhihao', 'Jia, Leili', 'Wang, Ligui', 'Hao, Rongzhang', 'Sun, Yansong', 'Huang, Liuyu', 'Ma, Hui', 'Yuan, Zhengquan', 'Song, Hongbin']",Sci Rep,,,False
8ca0739bd39a043e0e9e2f67f58e899497d2658e,PMC,Targeted Collection of Plasmid DNA in Large and Growing Animal Muscles 6 Weeks after DNA Vaccination with and without Electroporation,http://dx.doi.org/10.1155/2015/326825,PMC4561992,26380318,CC BY,"DNA vaccination has been developed in the last two decades in human and animal species as a promising alternative to conventional vaccination. It consists in the injection, in the muscle, for example, of plasmid DNA encoding the vaccinating polypeptide. Electroporation which forces the entrance of the plasmid DNA in cells at the injection point has been described as a powerful and promising strategy to enhance DNA vaccine efficacy. Due to the fact that the vaccine is composed of DNA, close attention on the fate of the plasmid DNA upon vaccination has to be taken into account, especially at the injection point. To perform such studies, the muscle injection point has to be precisely recovered and collected several weeks after injection. This is even more difficult for large and growing animals. A technique has been developed to localize precisely and collect efficiently the muscle injection points in growing piglets 6 weeks after DNA vaccination accompanied or not by electroporation. Electroporation did not significantly increase the level of remaining plasmids compared to nonelectroporated piglets, and, in all the cases, the levels were below the limit recommended by the FDA to research integration events of plasmid DNA into the host DNA.",2015 Aug 25,"['Dory, Daniel', 'Le Moigne, Vincent', 'Cariolet, Roland', 'Béven, Véronique', ""Keranflec'h, André"", 'Jestin, André']",J Immunol Res,,,True
f3284e9c3eef64c4badcedf21d266309a360374a,PMC,Controlled Microwave Heating Accelerates Rolling Circle Amplification,http://dx.doi.org/10.1371/journal.pone.0136532,PMC4562646,26348227,CC BY,"Rolling circle amplification (RCA) generates single-stranded DNAs or RNA, and the diverse applications of this isothermal technique range from the sensitive detection of nucleic acids to analysis of single nucleotide polymorphisms. Microwave chemistry is widely applied to increase reaction rate as well as product yield and purity. The objectives of the present research were to apply microwave heating to RCA and indicate factors that contribute to the microwave selective heating effect. The microwave reaction temperature was strictly controlled using a microwave applicator optimized for enzymatic-scale reactions. Here, we showed that microwave-assisted RCA reactions catalyzed by either of the four thermostable DNA polymerases were accelerated over 4-folds compared with conventional RCA. Furthermore, the temperatures of the individual buffer components were specifically influenced by microwave heating. We concluded that microwave heating accelerated isothermal RCA of DNA because of the differential heating mechanisms of microwaves on the temperatures of reaction components, although the overall reaction temperatures were the same.",2015 Sep 8,"['Yoshimura, Takeo', 'Suzuki, Takamasa', 'Mineki, Shigeru', 'Ohuchi, Shokichi']",PLoS One,,,True
ddf124684188ac29dba3b174f327bd0fd62155bd,PMC,"Co-Circulation of the Rare CPV-2c with Unique Gln370Arg Substitution, New CPV-2b with Unique Thr440Ala Substitution, and New CPV-2a with High Prevalence and Variation in Heilongjiang Province, Northeast China",http://dx.doi.org/10.1371/journal.pone.0137288,PMC4562665,26348721,CC BY,"To trace evolution of canine parvovirus-2 (CPV-2), a total of 201 stool samples were collected from dogs with diarrhea in Heilongjiang province of northeast China from May 2014 to April 2015. The presence of CPV-2 in the samples was determined by PCR amplification of the VP2 gene (568 bp) of CPV-2. The results revealed that 95 samples (47.26%) were positive for CPV-2, and they showed 98.8%–100% nucleotide identity and 97.6%–100% amino acid identity. Of 95 CPV-2-positive samples, types new2a (Ser297Ala), new2b (Ser297Ala), and 2c accounted for 64.21%, 21.05%, and 14.74%, respectively. The positive rate of CPV-2 and the distribution of the new2a, new2b and 2c types exhibited differences among regions, seasons, and ages. Immunized dogs accounted for 48.42% of 95 CPV-2-positive samples. Coinfections with canine coronavirus, canine kobuvirus, and canine bocavirus were identified. Phylogenetic analysis revealed that the identified new2a, new2b, and CPV-2c strains in our study exhibited a close relationship with most of the CPV-2 strains from China; type new2a strains exhibited high variability, forming three subgroups; type new2b and CPV-2c strains formed one group with reference strains from China. Of 95 CPV-2 strains, Tyr324Ile and Thr440Ala substitutions accounted for 100% and 64.21%, respectively; all type new2b strains exhibited the Thr440Ala substitution, while the unique Gln370Arg substitution was found in all type 2c strains. Recombination analysis using entire VP2 gene indicated possible recombination events between the identified CPV-2 strains and reference strains from China. Our data revealed the co-circulation of new CPV-2a, new CPV-2b, and rare CPV-2c, as well as potential recombination events among Chinese CPV-2 strains.",2015 Sep 8,"['Geng, Yufei', 'Guo, Donghua', 'Li, Chunqiu', 'Wang, Enyu', 'Wei, Shan', 'Wang, Zhihui', 'Yao, Shuang', 'Zhao, Xiwen', 'Su, Mingjun', 'Wang, Xinyu', 'Wang, Jianfa', 'Wu, Rui', 'Feng, Li', 'Sun, Dongbo']",PLoS One,,,True
5c6b707c8cbd087e87e1a1c1f2e809cffc96a9dc,PMC,Evolutionary History of the Photolyase/Cryptochrome Superfamily in Eukaryotes,http://dx.doi.org/10.1371/journal.pone.0135940,PMC4564169,26352435,CC BY,"BACKGROUND: Photolyases and cryptochromes are evolutionarily related flavoproteins, which however perform distinct physiological functions. Photolyases (PHR) are evolutionarily ancient enzymes. They are activated by light and repair DNA damage caused by UV radiation. Although cryptochromes share structural similarity with DNA photolyases, they lack DNA repair activity. Cryptochrome (CRY) is one of the key elements of the circadian system in animals. In plants, CRY acts as a blue light receptor to entrain circadian rhythms, and mediates a variety of light responses, such as the regulation of flowering and seedling growth. RESULTS: We performed a comprehensive evolutionary analysis of the CRY/PHR superfamily. The superfamily consists of 7 major subfamilies: CPD class I and CPD class II photolyases, (6–4) photolyases, CRY-DASH, plant PHR2, plant CRY and animal CRY. Although the whole superfamily evolved primarily under strong purifying selection (average ω = 0.0168), some subfamilies did experience strong episodic positive selection during their evolution. Photolyases were lost in higher animals that suggests natural selection apparently became weaker in the late stage of evolutionary history. The evolutionary time estimates suggested that plant and animal CRYs evolved in the Neoproterozoic Era (~1000–541 Mya), which might be a result of adaptation to the major climate and global light regime changes occurred in that period of the Earth’s geological history.",2015 Sep 9,"['Mei, Qiming', 'Dvornyk, Volodymyr']",PLoS One,,,True
84b4f6a6bca69d4387ae4f6c276ce370a9def7c9,PMC,Bayesian mixture analysis for metagenomic community profiling,http://dx.doi.org/10.1093/bioinformatics/btv317,PMC4565032,26002885,CC BY,"Motivation: Deep sequencing of clinical samples is now an established tool for the detection of infectious pathogens, with direct medical applications. The large amount of data generated produces an opportunity to detect species even at very low levels, provided that computational tools can effectively profile the relevant metagenomic communities. Data interpretation is complicated by the fact that short sequencing reads can match multiple organisms and by the lack of completeness of existing databases, in particular for viral pathogens. Here we present metaMix, a Bayesian mixture model framework for resolving complex metagenomic mixtures. We show that the use of parallel Monte Carlo Markov chains for the exploration of the species space enables the identification of the set of species most likely to contribute to the mixture. Results: We demonstrate the greater accuracy of metaMix compared with relevant methods, particularly for profiling complex communities consisting of several related species. We designed metaMix specifically for the analysis of deep transcriptome sequencing datasets, with a focus on viral pathogen detection; however, the principles are generally applicable to all types of metagenomic mixtures. Availability and implementation: metaMix is implemented as a user friendly R package, freely available on CRAN: http://cran.r-project.org/web/packages/metaMix Contact: sofia.morfopoulou.10@ucl.ac.uk Supplementary information: Supplementary data are available at Bionformatics online.",2015 Sep 15,"['Morfopoulou, Sofia', 'Plagnol, Vincent']",Bioinformatics,,,True
2c96f822b3f2e493aedeaa1b3b0e32e0819dbd5b,PMC,Bayesian mixture analysis for metagenomic community profiling,http://dx.doi.org/10.1093/bioinformatics/btv317,PMC4565032,26002885,CC BY,"Motivation: Deep sequencing of clinical samples is now an established tool for the detection of infectious pathogens, with direct medical applications. The large amount of data generated produces an opportunity to detect species even at very low levels, provided that computational tools can effectively profile the relevant metagenomic communities. Data interpretation is complicated by the fact that short sequencing reads can match multiple organisms and by the lack of completeness of existing databases, in particular for viral pathogens. Here we present metaMix, a Bayesian mixture model framework for resolving complex metagenomic mixtures. We show that the use of parallel Monte Carlo Markov chains for the exploration of the species space enables the identification of the set of species most likely to contribute to the mixture. Results: We demonstrate the greater accuracy of metaMix compared with relevant methods, particularly for profiling complex communities consisting of several related species. We designed metaMix specifically for the analysis of deep transcriptome sequencing datasets, with a focus on viral pathogen detection; however, the principles are generally applicable to all types of metagenomic mixtures. Availability and implementation: metaMix is implemented as a user friendly R package, freely available on CRAN: http://cran.r-project.org/web/packages/metaMix Contact: sofia.morfopoulou.10@ucl.ac.uk Supplementary information: Supplementary data are available at Bionformatics online.",2015 Sep 15,"['Morfopoulou, Sofia', 'Plagnol, Vincent']",Bioinformatics,,,False
154eae1741c2ed718dec40b25f60eca4b56e0a74,PMC,Fiat Luc: Bioluminescence Imaging Reveals In Vivo Viral Replication Dynamics,http://dx.doi.org/10.1371/journal.ppat.1005081,PMC4565549,26356297,CC BY,,2015 Sep 10,"Mehle, Andrew",PLoS Pathog,,,True
1e8ec294fcc4507fcc89872f84adcf4633bb10e6,PMC,Evaluation of Commercial Diagnostic Assays for the Specific Detection of Avian Influenza A (H7N9) Virus RNA Using a Quality-Control Panel and Clinical Specimens in China,http://dx.doi.org/10.1371/journal.pone.0137862,PMC4567293,26361351,CC BY,"A novel avian influenza A H7N9-subtype virus emerged in China in 2013 and threatened global public health. Commercial kits that specifically detect avian influenza A (H7N9) virus RNA are urgently required to prepare for the emergence and potential pandemic of this novel influenza virus. The safety and effectiveness of three commercial molecular diagnostic assays were evaluated using a quality-control panel and clinical specimens collected from over 90 patients with confirmed avian influenza A (H7N9) virus infections. The analytical performance evaluation showed that diverse influenza H7N9 viruses can be detected with high within- and between-lot reproducibility and without cross-reactivity to other influenza viruses (H1N1 pdm09, seasonal H1N1, H3N2, H5N1 and influenza B). The detection limit of all the commercial assays was 2.83 Log(10) copies/μl [0.7 Log(10)TCID(50)/mL of avian influenza A (H7N9) virus strain A/Zhejiang/DTID-ZJU01/2013], which is comparable to the method recommended by the World Health Organization (WHO). In addition, using a WHO-Chinese National Influenza Center (CNIC) method as a reference for clinical evaluation, positive agreement of more than 98% was determined for all of the commercial kits, while negative agreement of more than 99% was observed. In conclusion, our findings provide comprehensive evidence for the high performance of three commercial diagnostic assays and suggest the application of these assays as rapid and effective diagnostic tools for avian influenza A (H7N9) virus in the routine clinical practice of medical laboratories.",2015 Sep 11,"['Shi, Dawei', 'Shen, Shu', 'Fan, Xingliang', 'Chen, Suhong', 'Wang, Dayan', 'Li, Changgui', 'Wu, Xing', 'Li, Lili', 'Bai, Dongting', 'Zhang, Chuntao', 'Wang, Junzhi']",PLoS One,,,True
f6df4efd2fd556e59aae0df8de281f84bf762dff,PMC,Changes in the Swine Gut Microbiota in Response to Porcine Epidemic Diarrhea Infection,http://dx.doi.org/10.1264/jsme2.ME15046,PMC4567570,26212519,CC BY,"The gastrointestinal tract of mammals is a complex ecosystem with distinct environments and comprises hundreds of different types of bacterial cells. The gut microbiota may play a critical role in the gut health of the host. We herein attempted to identify a microbiota shift that may be affected by porcine epidemic diarrhea (PED). We observed significant differences in microbiota between the control and PED virus (PEDV)-infected groups at both the phylum and genus level. Most commensal bacteria (i.e. Psychrobacter, Prevotella, and Faecalibacterium) in the healthy gastrointestinal tract were decreased due to dysbiosis induced by PEDV infection.",2015 Sep 25,"['Koh, Hyeon-Woo', 'Kim, Myun Soo', 'Lee, Jong-Soo', 'Kim, Hongik', 'Park, Soo-Je']",Microbes Environ,,,True
9f4050b9399c1b4b744d79edca2d37ed021ad362,PMC,Changes in the Swine Gut Microbiota in Response to Porcine Epidemic Diarrhea Infection,http://dx.doi.org/10.1264/jsme2.ME15046,PMC4567570,26212519,CC BY,"The gastrointestinal tract of mammals is a complex ecosystem with distinct environments and comprises hundreds of different types of bacterial cells. The gut microbiota may play a critical role in the gut health of the host. We herein attempted to identify a microbiota shift that may be affected by porcine epidemic diarrhea (PED). We observed significant differences in microbiota between the control and PED virus (PEDV)-infected groups at both the phylum and genus level. Most commensal bacteria (i.e. Psychrobacter, Prevotella, and Faecalibacterium) in the healthy gastrointestinal tract were decreased due to dysbiosis induced by PEDV infection.",2015 Sep 25,"['Koh, Hyeon-Woo', 'Kim, Myun Soo', 'Lee, Jong-Soo', 'Kim, Hongik', 'Park, Soo-Je']",Microbes Environ,,,True
1e9719d2d1a523240172b19f822f7a956c553fdf,PMC,Evaluation of applied public health emergency system at Prince Mohammed International Airport in Almedinah during Hajj season 2014: a qualitative case study,http://dx.doi.org/10.1186/s13104-015-1415-2,PMC4568065,26364051,CC BY,"BACKGROUND: During the Hajj season 2014, several public health measures were applied by the Ministry of Health at Prince Mohammed International Airport in Almedinah. However, several operational defects affected the provision of preventive health services for passengers and airport workers. This study aims to evaluate the applied public health emergency system at the airport, detect any potential gaps and to provide appropriate operational solutions. METHODS: This is a qualitative case study conducted at Prince Mohammed International Airport in Almedinah during the 2014 Hajj season, September 2014. Data were collected via semi-structured interviews, focus groups and policy document reviews. Interviews were conducted with the 14 individuals of the airport’s decision makers and relevant health practitioners. Data were recorded via taking notes during interviews and data coding was performed to produce the main themes and subthemes of the study. RESULTS: The main findings of the study revealed three main defects affecting the applied public health emergency system at the airport. The main themes were mainly related to shortage in logistics related to public health emergency systems, shortage in proper documentation of policies and lack of documented protocols of communications among airport stakeholders. CONCLUSIONS: The study highlighted the main factors hindering the application of public health emergency measures at the airport. A Public Health Emergency Contingency Plan was proposed as a method to regulate the process of providing logistics for public health preventive services, the method of producing documented policies and methods of producing Memoranda of Understandings as communication regulators.",2015 Sep 12,"['Gosadi, Ibrahim M.', 'BinSaeed, Abdulaziz', 'Al-Hazmi, Ali M.', 'Fadl, Amin A.', 'Alharbi, Khalid H.', 'Swarelzahab, Mazin M.']",BMC Res Notes,,,True
dd9f6d51d902c4493f797715278469d4c19bf65d,PMC,The NLRP3 Inflammasome and IL-1β Accelerate Immunologically Mediated Pathology in Experimental Viral Fulminant Hepatitis,http://dx.doi.org/10.1371/journal.ppat.1005155,PMC4569300,26367131,CC0,"Viral fulminant hepatitis (FH) is a severe disease with high mortality resulting from excessive inflammation in the infected liver. Clinical interventions have been inefficient due to the lack of knowledge for inflammatory pathogenesis in the virus-infected liver. We show that wild-type mice infected with murine hepatitis virus strain-3 (MHV-3), a model for viral FH, manifest with severe disease and high mortality in association with a significant elevation in IL-1β expression in the serum and liver. Whereas, the viral infection in IL-1β receptor-I deficient (IL-1R1 (-/-)) or IL-1R antagonist (IL-1Ra) treated mice, show reductions in virus replication, disease progress and mortality. IL-1R1 deficiency appears to debilitate the virus-induced fibrinogen-like protein-2 (FGL2) production in macrophages and CD45(+)Gr-1(high) neutrophil infiltration in the liver. The quick release of reactive oxygen species (ROS) by the infected macrophages suggests a plausible viral initiation of NLRP3 inflammasome activation. Further experiments show that mice deficient of p47 (phox), a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit that controls acute ROS production, present with reductions in NLRP3 inflammasome activation and subsequent IL-1β secretion during viral infection, which appears to be responsible for acquiring resilience to viral FH. Moreover, viral infected animals in deficiencies of NLRP3 and Caspase-1, two essential components of the inflammasome complex, also have reduced IL-1β induction along with ameliorated hepatitis. Our results demonstrate that the ROS/NLRP3/IL-1β axis institutes an essential signaling pathway, which is over activated and directly causes the severe liver disease during viral infection, which sheds light on development of efficient treatments for human viral FH and other severe inflammatory diseases.",2015 Sep 14,"['Guo, Sheng', 'Yang, Chengying', 'Diao, Bo', 'Huang, Xiaoyong', 'Jin, Meihua', 'Chen, Lili', 'Yan, Weiming', 'Ning, Qin', 'Zheng, Lixin', 'Wu, Yuzhang', 'Chen, Yongwen']",PLoS Pathog,,,True
0b0208d63d06379d846edf649d47041fc2c1aa86,PMC,Live Poultry Exposure and Public Response to Influenza A(H7N9) in Urban and Rural China during Two Epidemic Waves in 2013-2014,http://dx.doi.org/10.1371/journal.pone.0137831,PMC4569561,26367002,CC BY,"BACKGROUND: The novel influenza A(H7N9) virus has caused 2013 spring and 2013–2014 winter waves of human infections since its first emergence in China in March 2013. Exposure to live poultry is a risk factor for H7N9 infection. Public psychobehavioral responses often change during progression of an epidemic. METHODS: We conducted population-based surveys in southern China to examine human exposure to live poultry, and population psychological response and behavioral changes in the two waves. In Guangzhou, an urban area of Guangdong province, we collected data using telephone surveys with random digit dialing in May-June 2013 and again in December 2013 to January 2014. In Zijin county, a rural area of the same province, we used door-to-door surveys under a stratified sampling design in July 2013 and again in December 2013 to January 2014. All responses were weighted by age and sex to the respective adult populations. FINDINGS: Around half of the urban respondents (53.8%) reported having visited LPMs in the previous year in the first survey, around double that reported in the second survey (27.7%). In the rural surveys, around half of the participants reported raising backyard poultry in the past year in the first survey, increasing to 83.2% participants in the second survey. One third of urban subjects supported the permanent closure of LPMs in the first and second surveys, and factors associated with support for closure included female sex, higher level of worry towards H7N9, and worry induced by a hypothetical influenza-like illness. CONCLUSIONS: Our study indicated high human exposure to live poultry and low support for permanent closure of markets in both urban and rural residents regardless of increased worry during the epidemic.",2015 Sep 14,"['Wu, Peng', 'Wang, Liping', 'Cowling, Benjamin J.', 'Yu, Jianxing', 'Fang, Vicky J.', 'Li, Fu', 'Zeng, Lingjia', 'Wu, Joseph T.', 'Li, Zhongjie', 'Leung, Gabriel M.', 'Yu, Hongjie']",PLoS One,,,True
9405b40aa26445cd02d7382bf256641ca774de46,PMC,Cholesteryl Pullulan Encapsulated TNF-α Nanoparticles Are an Effective Mucosal Vaccine Adjuvant against Influenza Virus,http://dx.doi.org/10.1155/2015/471468,PMC4569761,26421290,CC BY,"We encapsulated tumor necrosis factor-α (TNF-α), a major proinflammatory cytokine, into cholesteryl pullulan (CHP) to prepare TNF/CHP nanoparticles. In this report, we describe the immune-enhancing capability of the nanoparticles to act as a vaccine adjuvant. TNF/CHP nanoparticles showed excellent storage stability and enhanced host immune responses to external immunogens. The nanoparticles were effective via the nasal route of administration for inducing systemic IgG(1) as well as mucosal IgA. We applied the nanoparticles in a model experimental influenza virus infection to investigate their adjuvant ability. TNF/CHP nanoparticles combined with a conventional split vaccine protected mice via nasal administration against a lethal challenge of A/PR/8/34 (H1N1) influenza virus. Mechanistic studies showed that the nanoparticles enhanced antigen uptake by dendritic cells (DCs) and moderately induced the expression of inflammation-related genes in nasopharynx lymphoid tissue (NALT), leading to the activation of both B and T cells. Preliminary safety study revealed no severe toxicity to TNF/CHP nanoparticles. Slight-to-moderate influences in nasal mucosa were observed only in the repeated administration and they seemed to be reversible. Our data show that TNF/CHP nanoparticles effectively enhance both humoral and cellular immunity and could be a potential adjuvant for vaccines against infectious diseases, especially in the mucosa.",2015 Sep 1,"['Nagatomo, Daiki', 'Taniai, Madoka', 'Ariyasu, Harumi', 'Taniguchi, Mutsuko', 'Aga, Miho', 'Ariyasu, Toshio', 'Ohta, Tsunetaka', 'Fukuda, Shigeharu']",Biomed Res Int,,,True
9a8d3c6485a6edc2e872b4aa7740a8e6d7ef9013,PMC,β(2)-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study,http://dx.doi.org/10.1186/s12881-015-0229-3,PMC4570703,26369942,CC BY,"BACKGROUND: Despite the significant interest in β(2)-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0229-3) contains supplementary material, which is available to authorized users.",2015 Sep 14,"['Wu, Pingsheng', 'Larkin, Emma K', 'Reiss, Sara S', 'Carroll, Kecia N', 'Summar, Marshall L', 'Minton, Patricia A', 'Woodward, Kimberly B', 'Liu, Zhouwen', 'Islam, Jessica Y', 'Hartert, Tina V', 'Moore, Paul E']",BMC Med Genet,,,False
d98a0e4da1857f0674df04073b816011e9c9938b,PMC,β(2)-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study,http://dx.doi.org/10.1186/s12881-015-0229-3,PMC4570703,26369942,CC BY,"BACKGROUND: Despite the significant interest in β(2)-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0229-3) contains supplementary material, which is available to authorized users.",2015 Sep 14,"['Wu, Pingsheng', 'Larkin, Emma K', 'Reiss, Sara S', 'Carroll, Kecia N', 'Summar, Marshall L', 'Minton, Patricia A', 'Woodward, Kimberly B', 'Liu, Zhouwen', 'Islam, Jessica Y', 'Hartert, Tina V', 'Moore, Paul E']",BMC Med Genet,,,False
e95a5be4b7bed3cc738acdf1e82e2b665c9c8cc4,PMC,β(2)-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study,http://dx.doi.org/10.1186/s12881-015-0229-3,PMC4570703,26369942,CC BY,"BACKGROUND: Despite the significant interest in β(2)-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0229-3) contains supplementary material, which is available to authorized users.",2015 Sep 14,"['Wu, Pingsheng', 'Larkin, Emma K', 'Reiss, Sara S', 'Carroll, Kecia N', 'Summar, Marshall L', 'Minton, Patricia A', 'Woodward, Kimberly B', 'Liu, Zhouwen', 'Islam, Jessica Y', 'Hartert, Tina V', 'Moore, Paul E']",BMC Med Genet,,,False
80e20f7b1fae3d4b8d7596cecd652ea4199549ec,PMC,β(2)-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study,http://dx.doi.org/10.1186/s12881-015-0229-3,PMC4570703,26369942,CC BY,"BACKGROUND: Despite the significant interest in β(2)-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0229-3) contains supplementary material, which is available to authorized users.",2015 Sep 14,"['Wu, Pingsheng', 'Larkin, Emma K', 'Reiss, Sara S', 'Carroll, Kecia N', 'Summar, Marshall L', 'Minton, Patricia A', 'Woodward, Kimberly B', 'Liu, Zhouwen', 'Islam, Jessica Y', 'Hartert, Tina V', 'Moore, Paul E']",BMC Med Genet,,,False
e67f8a93050b2405a8d6035a34d26644443d41d3,PMC,β(2)-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study,http://dx.doi.org/10.1186/s12881-015-0229-3,PMC4570703,26369942,CC BY,"BACKGROUND: Despite the significant interest in β(2)-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0229-3) contains supplementary material, which is available to authorized users.",2015 Sep 14,"['Wu, Pingsheng', 'Larkin, Emma K', 'Reiss, Sara S', 'Carroll, Kecia N', 'Summar, Marshall L', 'Minton, Patricia A', 'Woodward, Kimberly B', 'Liu, Zhouwen', 'Islam, Jessica Y', 'Hartert, Tina V', 'Moore, Paul E']",BMC Med Genet,,,False
fab662f7ae1f1e7ee94023c90461dba3092f915c,PMC,β(2)-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study,http://dx.doi.org/10.1186/s12881-015-0229-3,PMC4570703,26369942,CC BY,"BACKGROUND: Despite the significant interest in β(2)-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0229-3) contains supplementary material, which is available to authorized users.",2015 Sep 14,"['Wu, Pingsheng', 'Larkin, Emma K', 'Reiss, Sara S', 'Carroll, Kecia N', 'Summar, Marshall L', 'Minton, Patricia A', 'Woodward, Kimberly B', 'Liu, Zhouwen', 'Islam, Jessica Y', 'Hartert, Tina V', 'Moore, Paul E']",BMC Med Genet,,,False
132e94687b6ac1d68f3a33dcf090bc6f5865bb98,PMC,β(2)-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study,http://dx.doi.org/10.1186/s12881-015-0229-3,PMC4570703,26369942,CC BY,"BACKGROUND: Despite the significant interest in β(2)-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0229-3) contains supplementary material, which is available to authorized users.",2015 Sep 14,"['Wu, Pingsheng', 'Larkin, Emma K', 'Reiss, Sara S', 'Carroll, Kecia N', 'Summar, Marshall L', 'Minton, Patricia A', 'Woodward, Kimberly B', 'Liu, Zhouwen', 'Islam, Jessica Y', 'Hartert, Tina V', 'Moore, Paul E']",BMC Med Genet,,,True
80229bc73fc274591a2f0c6472a0d8c6fb966dd0,PMC,ADAP2 Is an Interferon Stimulated Gene That Restricts RNA Virus Entry,http://dx.doi.org/10.1371/journal.ppat.1005150,PMC4570769,26372645,CC BY,"Interferon stimulated genes (ISGs) target viruses at various stages of their infectious life cycles, including at the earliest stage of viral entry. Here we identify ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2) as a gene upregulated by type I IFN treatment in a STAT1-dependent manner. ADAP2 functions as a GTPase-activating protein (GAP) for Arf6 and binds to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P(3)) and PI(3,4)P(2). We show that overexpression of ADAP2 suppresses dengue virus (DENV) and vesicular stomatitis virus (VSV) infection in an Arf6 GAP activity-dependent manner, while exerting no effect on coxsackievirus B (CVB) or Sendai virus (SeV) replication. We further show that ADAP2 expression induces macropinocytosis and that ADAP2 strongly associates with actin-enriched membrane ruffles and with Rab8a- and LAMP1-, but not EEA1- or Rab7-, positive vesicles. Utilizing two techniques—light-sensitive neutral red (NR)-containing DENV and fluorescence assays for virus internalization—we show that ADAP2 primarily restricts DENV infection at the stage of virion entry and/or intracellular trafficking and that incoming DENV and VSV particles associate with ADAP2 during their entry. Taken together, this study identifies ADAP2 as an ISG that exerts antiviral effects against RNA viruses by altering Arf6-mediated trafficking to disrupt viral entry.",2015 Sep 15,"['Shu, Qian', 'Lennemann, Nicholas J.', 'Sarkar, Saumendra N.', 'Sadovsky, Yoel', 'Coyne, Carolyn B.']",PLoS Pathog,,,True
624840869f8c5f365a639a67cae53f56c740749f,PMC,Early real-time estimation of the basic reproduction number of emerging or reemerging infectious diseases in a community with heterogeneous contact pattern: Using data from Hong Kong 2009 H1N1 Pandemic Influenza as an illustrative example,http://dx.doi.org/10.1371/journal.pone.0137959,PMC4570805,26372219,CC BY,"Emerging and re-emerging infections such as SARS (2003) and pandemic H1N1 (2009) have caused concern for public health researchers and policy makers due to the increased burden of these diseases on health care systems. This concern has prompted the use of mathematical models to evaluate strategies to control disease spread, making these models invaluable tools to identify optimal intervention strategies. A particularly important quantity in infectious disease epidemiology is the basic reproduction number, R(0.) Estimation of this quantity is crucial for effective control responses in the early phase of an epidemic. In our previous study, an approach for estimating the basic reproduction number in real time was developed. This approach uses case notification data and the structure of potential transmission contacts to accurately estimate R(0) from the limited amount of information available at the early stage of an outbreak. Based on this approach, we extend the existing methodology; the most recent method features intra- and inter-age groups contact heterogeneity. Given the number of newly reported cases at the early stage of the outbreak, with parsimony assumptions on removal distribution and infectivity profile of the diseases, experiments to estimate real time R(0) under different levels of intra- and inter-group contact heterogeneity using two age groups are presented. We show that the new method converges more quickly to the actual value of R(0) than the previous one, in particular when there is high-level intra-group and inter-group contact heterogeneity. With the age specific contact patterns, number of newly reported cases, removal distribution, and information about the natural history of the 2009 pandemic influenza in Hong Kong, we also use the extended model to estimate R(0) and age-specific R(0).",2015 Sep 15,"['Kwok, Kin On', 'Davoudi, Bahman', 'Riley, Steven', 'Pourbohloul, Babak']",PLoS One,,,True
75622daf6a8bde4809687a432c5bd991d8a849ea,PMC,Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody,http://dx.doi.org/10.1038/ncomms9223,PMC4571279,26370782,CC BY,"The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (∼36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of binding at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.",2015 Sep 15,"['Ying, Tianlei', 'Prabakaran, Ponraj', 'Du, Lanying', 'Shi, Wei', 'Feng, Yang', 'Wang, Yanping', 'Wang, Lingshu', 'Li, Wei', 'Jiang, Shibo', 'Dimitrov, Dimiter S.', 'Zhou, Tongqing']",Nat Commun,,,True
bf0a836e3d8d863356950aa4a760e449e5129792,PMC,Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody,http://dx.doi.org/10.1038/ncomms9223,PMC4571279,26370782,CC BY,"The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (∼36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of binding at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.",2015 Sep 15,"['Ying, Tianlei', 'Prabakaran, Ponraj', 'Du, Lanying', 'Shi, Wei', 'Feng, Yang', 'Wang, Yanping', 'Wang, Lingshu', 'Li, Wei', 'Jiang, Shibo', 'Dimitrov, Dimiter S.', 'Zhou, Tongqing']",Nat Commun,,,True
f4cd52975e6aa33e8c947082eda9b261952b0f8f,PMC,Metabolic engineering of Escherichia coli into a versatile glycosylation platform: production of bio-active quercetin glycosides,http://dx.doi.org/10.1186/s12934-015-0326-1,PMC4573293,26377568,CC BY,"BACKGROUND: Flavonoids are bio-active specialized plant metabolites which mainly occur as different glycosides. Due to the increasing market demand, various biotechnological approaches have been developed which use Escherichia coli as a microbial catalyst for the stereospecific glycosylation of flavonoids. Despite these efforts, most processes still display low production rates and titers, which render them unsuitable for large-scale applications. RESULTS: In this contribution, we expanded a previously developed in vivo glucosylation platform in E. coli W, into an efficient system for selective galactosylation and rhamnosylation. The rational of the novel metabolic engineering strategy constitutes of the introduction of an alternative sucrose metabolism in the form of a sucrose phosphorylase, which cleaves sucrose into fructose and glucose 1-phosphate as precursor for UDP-glucose. To preserve these intermediates for glycosylation purposes, metabolization reactions were knocked-out. Due to the pivotal role of UDP-glucose, overexpression of the interconverting enzymes galE and MUM4 ensured the formation of both UDP-galactose and UDP-rhamnose, respectively. By additionally supplying exogenously fed quercetin and overexpressing a flavonol galactosyltransferase (F3GT) or a rhamnosyltransferase (RhaGT), 0.94 g/L hyperoside (quercetin 3-O-galactoside) and 1.12 g/L quercitrin (quercetin 3-O-rhamnoside) could be produced, respectively. In addition, both strains showed activity towards other promising dietary flavonols like kaempferol, fisetin, morin and myricetin. CONCLUSIONS: Two E. coli W mutants were engineered that could effectively produce the bio-active flavonol glycosides hyperoside and quercitrin starting from the cheap substrates sucrose and quercetin. This novel fermentation-based glycosylation strategy will allow the economically viable production of various glycosides. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12934-015-0326-1) contains supplementary material, which is available to authorized users.",2015 Sep 16,"['De Bruyn, Frederik', 'Van Brempt, Maarten', 'Maertens, Jo', 'Van Bellegem, Wouter', 'Duchi, Dries', 'De Mey, Marjan']",Microb Cell Fact,,,True
427c25eb5418afb2f27b6f27b6c7c07b4ea7af08,PMC,Lactic acid bacteria: reviewing the potential of a promising delivery live vector for biomedical purposes,http://dx.doi.org/10.1186/s12934-015-0313-6,PMC4573465,26377321,CC BY,"Lactic acid bacteria (LAB) have a long history of safe exploitation by humans, being used for centuries in food production and preservation and as probiotic agents to promote human health. Interestingly, some species of these Gram-positive bacteria, which are generally recognized as safe organisms by the US Food and Drug Administration (FDA), are able to survive through the gastrointestinal tract (GIT), being capable to reach and colonize the intestine, where they play an important role. Besides, during the last decades, an important effort has been done for the development of tools to use LAB as microbial cell factories for the production of proteins of interest. Given the need to develop effective strategies for the delivery of prophylactic and therapeutic molecules, LAB have appeared as an appealing option for the oral, intranasal and vaginal delivery of such molecules. So far, these genetically modified organisms have been successfully used as vehicles for delivering functional proteins to mucosal tissues in the treatment of many different pathologies including GIT related pathologies, diabetes, cancer and viral infections, among others. Interestingly, the administration of such microorganisms would suppose a significant decrease in the production cost of the treatments agents since being live organisms, such vectors would be able to autonomously amplify and produce and deliver the protein of interest. In this context, this review aims to provide an overview of the use of LAB engineered as a promising alternative as well as a safety delivery platform of recombinant proteins for the treatment of a wide range of diseases.",2015 Sep 16,"['Cano-Garrido, Olivia', 'Seras-Franzoso, Joaquin', 'Garcia-Fruitós, Elena']",Microb Cell Fact,,,True
e658837e4d77ef0bccdd849648e2db595f5ec65b,PMC,Survey of Ixodes pacificus Ticks in California Reveals a Diversity of Microorganisms and a Novel and Widespread Anaplasmataceae Species,http://dx.doi.org/10.1371/journal.pone.0135828,PMC4574436,26375033,CC BY,"Ixodes pacificus ticks can harbor a wide range of human and animal pathogens. To survey the prevalence of tick-borne known and putative pathogens, we tested 982 individual adult and nymphal I. pacificus ticks collected throughout California between 2007 and 2009 using a broad-range PCR and electrospray ionization mass spectrometry (PCR/ESI-MS) assay designed to detect a wide range of tick-borne microorganisms. Overall, 1.4% of the ticks were found to be infected with Borrelia burgdorferi, 2.0% were infected with Borrelia miyamotoi and 0.3% were infected with Anaplasma phagocytophilum. In addition, 3.0% were infected with Babesia odocoilei. About 1.2% of the ticks were co-infected with more than one pathogen or putative pathogen. In addition, we identified a novel Anaplasmataceae species that we characterized by sequencing of its 16S rRNA, groEL, gltA, and rpoB genes. Sequence analysis indicated that this organism is phylogenetically distinct from known Anaplasma species with its closest genetic near neighbors coming from Asia. The prevalence of this novel Anaplasmataceae species was as high as 21% at one site, and it was detected in 4.9% of ticks tested statewide. Based upon this genetic characterization we propose that this organism be called ‘Candidatus Cryptoplasma californiense’. Knowledge of this novel microbe will provide awareness for the community about the breadth of the I. pacificus microbiome, the concept that this bacterium could be more widely spread; and an opportunity to explore whether this bacterium also contributes to human or animal disease burden.",2015 Sep 16,"['Eshoo, Mark W.', 'Carolan, Heather E.', 'Massire, Christian', 'Chou, Danny M.', 'Crowder, Chris D.', 'Rounds, Megan A.', 'Phillipson, Curtis A.', 'Schutzer, Steven E.', 'Ecker, David J.']",PLoS One,,,True
6548b941beede8bb57cde83a928e4383b54697ad,PMC,"Povidone-iodine hand wash and hand rub products demonstrated excellent in vitro virucidal efficacy against Ebola virus and modified vaccinia virus Ankara, the new European test virus for enveloped viruses",http://dx.doi.org/10.1186/s12879-015-1111-9,PMC4574578,26381737,CC BY,"BACKGROUND: The recent Ebola virus (EBOV) epidemic highlights the need for efficacious virucidal products to help prevent infection and limit the spread of Ebola virus disease. However, there is limited data on the efficacy of virucidal products against EBOV, because the virus has a high biosafety level and is only available in a few laboratories worldwide. The virucidal efficacy of antiseptics and disinfectants can be determined using the European Standard EN14476:2013/FprA1:2015. Modified vaccinia virus Ankara (MVA) was introduced in 2014 as a reference virus for the claim ‘virucidal active against enveloped viruses for hygienic hand rub and hand wash’. For EBOV, also an enveloped virus, the suitability of MVA as a surrogate needs to be proven. The aim of this study was to test the in vitro efficacy of four povidone iodine (PVP-I) formulations against EBOV: 4 % PVP-I skin cleanser; 7.5 % PVP-I surgical scrub; 10 % PVP-I solution; and 3.2 % PVP-I and 78 % alcohol solution. The formulations were tested with MVA to define the test conditions, and as a secondary objective the suitability of MVA as a surrogate for enveloped viruses like EBOV was assessed. METHODS: According to EN14476, a standard suspension test was used for MVA. Large-volume plating was used for EBOV to increase test sensitivity and exclude potential after-effects. All products were tested under clean (0.3 g/L BSA) and dirty (3.0 g/L BSA + 3.0 mL/L erythrocytes) conditions with MVA for 15, 30, and 60 s. The concentration-contact time values obtained with MVA were verified for EBOV. RESULTS: Viral titres of MVA and EBOV were reduced by >99.99 % to >99.999 % under clean and dirty conditions after application of the test products for 15 seconds. CONCLUSIONS: All products showed excellent virucidal efficacy against EBOV, demonstrating the important role PVP-I can play in helping to prevent and limit the spread of Ebola virus disease. The efficacy against both test viruses after 15 s is helpful information for the implementation of guidance for people potentially exposed to EBOV, and confirms the excellent virucidal efficacy of PVP-I against enveloped viruses. MVA was found to be a suitable surrogate for enveloped viruses like EBOV.",2015 Sep 17,"['Eggers, Maren', 'Eickmann, Markus', 'Kowalski, Katharina', 'Zorn, Juergen', 'Reimer, Karen']",BMC Infect Dis,,,True
8f962ad62ba3d5af7c52898283c4827ff71a5949,PMC,TMPRSS2 Isoform 1 Activates Respiratory Viruses and Is Expressed in Viral Target Cells,http://dx.doi.org/10.1371/journal.pone.0138380,PMC4574978,26379044,CC BY,"The cellular protease TMPRSS2 cleaves and activates the influenza virus hemagglutinin (HA) and TMPRSS2 expression is essential for viral spread and pathogenesis in mice. Moreover, severe acute respiratory syndrome coronavirus (SARS-CoV) and other respiratory viruses are activated by TMPRSS2. However, previous studies on viral activation by TMPRSS2 focused on a 492 amino acids comprising form of the protein (isoform 2) while other TMPRSS2 isoforms, generated upon alternative splicing of the tmprss2 mRNA, have not been characterized. Here, we show that the mRNA encoding a TMPRSS2 isoform with an extended N-terminal cytoplasmic domain (isoform 1) is expressed in lung-derived cell lines and tissues. Moreover, we demonstrate that TMPRSS2 isoform 1 colocalizes with HA and cleaves and activates HA. Finally, we show that isoform 1 activates the SARS-CoV spike protein for cathepsin L-independent entry into target cells. Our results indicate that TMPRSS2 isoform 1 is expressed in viral target cells and might contribute to viral activation in the host.",2015 Sep 17,"['Zmora, Pawel', 'Moldenhauer, Anna-Sophie', 'Hofmann-Winkler, Heike', 'Pöhlmann, Stefan']",PLoS One,,,True
9d18d8401ce2aa056ff228fce06c4a2d8c7f67f0,PMC,Transcriptome Analysis Reveals the Mechanism Underlying the Production of a High Quantity of Chlorogenic Acid in Young Leaves of Lonicera macranthoides Hand.-Mazz,http://dx.doi.org/10.1371/journal.pone.0137212,PMC4575056,26381882,CC BY,"Lonicera macranthoides Hand.-Mazz (L. macranthoides) is a medicinal herb that is widely distributed in southern China. The biosynthetic and metabolic pathways for a core secondary metabolite in L. macranthoides, chlorogenic acid (CGA), have been elucidated in many species. However, the mechanisms of CGA biosynthesis and the related gene regulatory network in L. macranthoides are still not well understood. In this study, CGA content was quantified by high performance liquid chromatography (HPLC), and CGA levels differed significantly among three tissues; specifically, the CGA content in young leaves (YL) was greater than that in young stems (YS), which was greater than that in mature flowers (MF). Transcriptome analysis of L. macranthoides yielded a total of 53,533,014 clean reads (average length 90 bp) and 76,453 unigenes (average length 703 bp). A total of 3,767 unigenes were involved in biosynthesis pathways of secondary metabolites. Of these unigenes, 80 were possibly related to CGA biosynthesis. Furthermore, differentially expressed genes (DEGs) were screened in different tissues including YL, MF and YS. In these tissues, 24 DEGs were found to be associated with CGA biosynthesis, including six phenylalanine ammonia lyase (PAL) genes, six 4-coumarate coenzyme A ligase (4CL) genes, four cinnamate 4-Hydroxylase (C4H) genes, seven hydroxycinnamoyl transferase/hydroxycinnamoyl-CoA quinate transferase HCT/HQT genes and one coumarate 3-hydroxylase (C3H) gene.These results further the understanding of CGA biosynthesis and the related regulatory network in L. macranthoides.",2015 Sep 18,"['Chen, Zexiong', 'Tang, Ning', 'You, Yuming', 'Lan, Jianbin', 'Liu, Yiqing', 'Li, Zhengguo']",PLoS One,,,True
59e339e8a09eb0b00c603cbd5867d8edabc2151d,PMC,Colorimetric Detection of Dengue by Single Tube Reverse-Transcription-Loop-Mediated Isothermal Amplification,http://dx.doi.org/10.1371/journal.pone.0138694,PMC4575147,26384248,CC BY,"Dengue is usually diagnosed by isolation of the virus, serology or molecular diagnostic methods. Several commercial kits for the diagnosis of dengue are existing, but concerns have arisen regarding to the affordability and performance characteristics of these kits. Hence, the loop-mediated isothermal amplification (LAMP) is potentially ideal to be used especially in resource limited environments. Serum was collected from healthy donors and patients diagnosed with dengue infection. RNA extracted from the serum samples were tested by reverse-transcription-LAMP assay developed based on 3′-NCR gene sequences for DENV 1–4. Results were interpreted by a turbidity meter in real time or visually at the end of the assay. Sensitivity and specificity of RT-LAMP results were calculated and compared to qRT-PCR and ELISA. RT-LAMP is highly sensitive with the detection limit of 10 RNA copies for all serotypes. Dengue virus RNA was detected in all positive samples using RT-LAMP and none of the negative samples within 30–45 minutes. With continuing efforts in the optimization of this assay, RT-LAMP may provide a simple and reliable test for detecting DENV in areas where dengue is prevalent.",2015 Sep 18,"['Lau, Yee-Ling', 'Lai, Meng-Yee', 'Teoh, Boon-Teong', 'Abd-Jamil, Juraina', 'Johari, Jefree', 'Sam, Sing-Sin', 'Tan, Kim-Kee', 'AbuBakar, Sazaly']",PLoS One,,,True
94f67a30df65c02cf339d2276e04afda40f59072,PMC,High-Throughput Ligand Discovery Reveals a Sitewise Gradient of Diversity in Broadly Evolved Hydrophilic Fibronectin Domains,http://dx.doi.org/10.1371/journal.pone.0138956,PMC4575168,26383268,CC BY,"Discovering new binding function via a combinatorial library in small protein scaffolds requires balance between appropriate mutations to introduce favorable intermolecular interactions while maintaining intramolecular integrity. Sitewise constraints exist in a non-spatial gradient from diverse to conserved in evolved antibody repertoires; yet non-antibody scaffolds generally do not implement this strategy in combinatorial libraries. Despite the fact that biased amino acid distributions, typically elevated in tyrosine, serine, and glycine, have gained wider use in synthetic scaffolds, these distributions are still predominantly applied uniformly to diversified sites. While select sites in fibronectin domains and DARPins have shown benefit from sitewise designs, they have not been deeply evaluated. Inspired by this disparity between diversity distributions in natural libraries and synthetic scaffold libraries, we hypothesized that binders resulting from discovery and evolution would exhibit a non-spatial, sitewise gradient of amino acid diversity. To identify sitewise diversities consistent with efficient evolution in the context of a hydrophilic fibronectin domain, >10(5) binders to six targets were evolved and sequenced. Evolutionarily favorable amino acid distributions at 25 sites reveal Shannon entropies (range: 0.3–3.9; median: 2.1; standard deviation: 1.1) supporting the diversity gradient hypothesis. Sitewise constraints in evolved sequences are consistent with complementarity, stability, and consensus biases. Implementation of sitewise constrained diversity enables direct selection of nanomolar affinity binders validating an efficient strategy to balance inter- and intra-molecular interaction demands at each site.",2015 Sep 18,"['Woldring, Daniel R.', 'Holec, Patrick V.', 'Zhou, Hong', 'Hackel, Benjamin J.']",PLoS One,,,True
5578dcb4f631bb4fabcf4d607327ee0bf1f133d1,PMC,High-Throughput Ligand Discovery Reveals a Sitewise Gradient of Diversity in Broadly Evolved Hydrophilic Fibronectin Domains,http://dx.doi.org/10.1371/journal.pone.0138956,PMC4575168,26383268,CC BY,"Discovering new binding function via a combinatorial library in small protein scaffolds requires balance between appropriate mutations to introduce favorable intermolecular interactions while maintaining intramolecular integrity. Sitewise constraints exist in a non-spatial gradient from diverse to conserved in evolved antibody repertoires; yet non-antibody scaffolds generally do not implement this strategy in combinatorial libraries. Despite the fact that biased amino acid distributions, typically elevated in tyrosine, serine, and glycine, have gained wider use in synthetic scaffolds, these distributions are still predominantly applied uniformly to diversified sites. While select sites in fibronectin domains and DARPins have shown benefit from sitewise designs, they have not been deeply evaluated. Inspired by this disparity between diversity distributions in natural libraries and synthetic scaffold libraries, we hypothesized that binders resulting from discovery and evolution would exhibit a non-spatial, sitewise gradient of amino acid diversity. To identify sitewise diversities consistent with efficient evolution in the context of a hydrophilic fibronectin domain, >10(5) binders to six targets were evolved and sequenced. Evolutionarily favorable amino acid distributions at 25 sites reveal Shannon entropies (range: 0.3–3.9; median: 2.1; standard deviation: 1.1) supporting the diversity gradient hypothesis. Sitewise constraints in evolved sequences are consistent with complementarity, stability, and consensus biases. Implementation of sitewise constrained diversity enables direct selection of nanomolar affinity binders validating an efficient strategy to balance inter- and intra-molecular interaction demands at each site.",2015 Sep 18,"['Woldring, Daniel R.', 'Holec, Patrick V.', 'Zhou, Hong', 'Hackel, Benjamin J.']",PLoS One,,,False
bb295c0aee03f7bed96537c61729f82ab14a3467,PMC,High-Throughput Ligand Discovery Reveals a Sitewise Gradient of Diversity in Broadly Evolved Hydrophilic Fibronectin Domains,http://dx.doi.org/10.1371/journal.pone.0138956,PMC4575168,26383268,CC BY,"Discovering new binding function via a combinatorial library in small protein scaffolds requires balance between appropriate mutations to introduce favorable intermolecular interactions while maintaining intramolecular integrity. Sitewise constraints exist in a non-spatial gradient from diverse to conserved in evolved antibody repertoires; yet non-antibody scaffolds generally do not implement this strategy in combinatorial libraries. Despite the fact that biased amino acid distributions, typically elevated in tyrosine, serine, and glycine, have gained wider use in synthetic scaffolds, these distributions are still predominantly applied uniformly to diversified sites. While select sites in fibronectin domains and DARPins have shown benefit from sitewise designs, they have not been deeply evaluated. Inspired by this disparity between diversity distributions in natural libraries and synthetic scaffold libraries, we hypothesized that binders resulting from discovery and evolution would exhibit a non-spatial, sitewise gradient of amino acid diversity. To identify sitewise diversities consistent with efficient evolution in the context of a hydrophilic fibronectin domain, >10(5) binders to six targets were evolved and sequenced. Evolutionarily favorable amino acid distributions at 25 sites reveal Shannon entropies (range: 0.3–3.9; median: 2.1; standard deviation: 1.1) supporting the diversity gradient hypothesis. Sitewise constraints in evolved sequences are consistent with complementarity, stability, and consensus biases. Implementation of sitewise constrained diversity enables direct selection of nanomolar affinity binders validating an efficient strategy to balance inter- and intra-molecular interaction demands at each site.",2015 Sep 18,"['Woldring, Daniel R.', 'Holec, Patrick V.', 'Zhou, Hong', 'Hackel, Benjamin J.']",PLoS One,,,False
68c511101e72f75c7c7146306567114789e25be4,PMC,High-Throughput Ligand Discovery Reveals a Sitewise Gradient of Diversity in Broadly Evolved Hydrophilic Fibronectin Domains,http://dx.doi.org/10.1371/journal.pone.0138956,PMC4575168,26383268,CC BY,"Discovering new binding function via a combinatorial library in small protein scaffolds requires balance between appropriate mutations to introduce favorable intermolecular interactions while maintaining intramolecular integrity. Sitewise constraints exist in a non-spatial gradient from diverse to conserved in evolved antibody repertoires; yet non-antibody scaffolds generally do not implement this strategy in combinatorial libraries. Despite the fact that biased amino acid distributions, typically elevated in tyrosine, serine, and glycine, have gained wider use in synthetic scaffolds, these distributions are still predominantly applied uniformly to diversified sites. While select sites in fibronectin domains and DARPins have shown benefit from sitewise designs, they have not been deeply evaluated. Inspired by this disparity between diversity distributions in natural libraries and synthetic scaffold libraries, we hypothesized that binders resulting from discovery and evolution would exhibit a non-spatial, sitewise gradient of amino acid diversity. To identify sitewise diversities consistent with efficient evolution in the context of a hydrophilic fibronectin domain, >10(5) binders to six targets were evolved and sequenced. Evolutionarily favorable amino acid distributions at 25 sites reveal Shannon entropies (range: 0.3–3.9; median: 2.1; standard deviation: 1.1) supporting the diversity gradient hypothesis. Sitewise constraints in evolved sequences are consistent with complementarity, stability, and consensus biases. Implementation of sitewise constrained diversity enables direct selection of nanomolar affinity binders validating an efficient strategy to balance inter- and intra-molecular interaction demands at each site.",2015 Sep 18,"['Woldring, Daniel R.', 'Holec, Patrick V.', 'Zhou, Hong', 'Hackel, Benjamin J.']",PLoS One,,,True
d06179d5a694b2d0a7e610a279739776ba33e1ae,PMC,High-Throughput Ligand Discovery Reveals a Sitewise Gradient of Diversity in Broadly Evolved Hydrophilic Fibronectin Domains,http://dx.doi.org/10.1371/journal.pone.0138956,PMC4575168,26383268,CC BY,"Discovering new binding function via a combinatorial library in small protein scaffolds requires balance between appropriate mutations to introduce favorable intermolecular interactions while maintaining intramolecular integrity. Sitewise constraints exist in a non-spatial gradient from diverse to conserved in evolved antibody repertoires; yet non-antibody scaffolds generally do not implement this strategy in combinatorial libraries. Despite the fact that biased amino acid distributions, typically elevated in tyrosine, serine, and glycine, have gained wider use in synthetic scaffolds, these distributions are still predominantly applied uniformly to diversified sites. While select sites in fibronectin domains and DARPins have shown benefit from sitewise designs, they have not been deeply evaluated. Inspired by this disparity between diversity distributions in natural libraries and synthetic scaffold libraries, we hypothesized that binders resulting from discovery and evolution would exhibit a non-spatial, sitewise gradient of amino acid diversity. To identify sitewise diversities consistent with efficient evolution in the context of a hydrophilic fibronectin domain, >10(5) binders to six targets were evolved and sequenced. Evolutionarily favorable amino acid distributions at 25 sites reveal Shannon entropies (range: 0.3–3.9; median: 2.1; standard deviation: 1.1) supporting the diversity gradient hypothesis. Sitewise constraints in evolved sequences are consistent with complementarity, stability, and consensus biases. Implementation of sitewise constrained diversity enables direct selection of nanomolar affinity binders validating an efficient strategy to balance inter- and intra-molecular interaction demands at each site.",2015 Sep 18,"['Woldring, Daniel R.', 'Holec, Patrick V.', 'Zhou, Hong', 'Hackel, Benjamin J.']",PLoS One,,,False
5bd910b6b8b82e7b70c97ebe2c34ad638236c67d,PMC,The Virus-Host Interplay: Biogenesis of +RNA Replication Complexes,http://dx.doi.org/10.3390/v7082825,PMC4576186,26287230,CC BY,"Positive-strand RNA (+RNA) viruses are an important group of human and animal pathogens that have significant global health and economic impacts. Notable members include West Nile virus, Dengue virus, Chikungunya, Severe acute respiratory syndrome (SARS) Coronavirus and enteroviruses of the Picornaviridae family.Unfortunately, prophylactic and therapeutic treatments against these pathogens are limited. +RNA viruses have limited coding capacity and thus rely extensively on host factors for successful infection and propagation. A common feature among these viruses is their ability to dramatically modify cellular membranes to serve as platforms for genome replication and assembly of new virions. These viral replication complexes (VRCs) serve two main functions: To increase replication efficiency by concentrating critical factors and to protect the viral genome from host anti-viral systems. This review summarizes current knowledge of critical host factors recruited to or demonstrated to be involved in the biogenesis and stabilization of +RNA virus VRCs.",2015 Aug 6,"['Reid, Colleen R.', 'Airo, Adriana M.', 'Hobman, Tom C.']",Viruses,,,True
1c07f420a5a01bec7481025a89f2621596a99782,PMC,Structural and Functional Properties of the Hepatitis C Virus p7 Viroporin,http://dx.doi.org/10.3390/v7082826,PMC4576187,26258788,CC BY,"The high prevalence of hepatitis C virus (HCV) infection in the human population has triggered intensive research efforts that have led to the development of curative antiviral therapy. Moreover, HCV has become a role model to study fundamental principles that govern the replication cycle of a positive strand RNA virus. In fact, for most HCV proteins high-resolution X-ray and NMR (Nuclear Magnetic Resonance)-based structures have been established and profound insights into their biochemical and biological properties have been gained. One example is p7, a small hydrophobic protein that is dispensable for RNA replication, but crucial for the production and release of infectious HCV particles from infected cells. Owing to its ability to insert into membranes and assemble into homo-oligomeric complexes that function as minimalistic ion channels, HCV p7 is a member of the viroporin family. This review compiles the most recent findings related to the structure and dual pore/ion channel activity of p7 of different HCV genotypes. The alternative conformations and topologies proposed for HCV p7 in its monomeric and oligomeric state are described and discussed in detail. We also summarize the different roles p7 might play in the HCV replication cycle and highlight both the ion channel/pore-like function and the additional roles of p7 unrelated to its channel activity. Finally, we discuss possibilities to utilize viroporin inhibitors for antagonizing p7 ion channel/pore-like activity.",2015 Aug 6,"['Madan, Vanesa', 'Bartenschlager, Ralf']",Viruses,,,True
b51c5f53980e0118362f26862e1243aac186a4ab,PMC,Genetic Characterization of the Belgian Nephropathogenic Infectious Bronchitis Virus (NIBV) Reference Strain B1648,http://dx.doi.org/10.3390/v7082827,PMC4576188,26262637,CC BY,"The virulent nephropathogenic infectious bronchitis virus (NIBV) strain B1648 was first isolated in 1984, in Flanders, Belgium. Despite intensive vaccination, B1648 and its variants are still circulating in Europe and North Africa. Here, the full-length genome of this Belgian NIBV reference strain was determined by next generation sequencing (NGS) to understand its evolutionary relationship with other IBV strains, and to identify possible genetic factors that may be associated with the nephropathogenicity. Thirteen open reading frames (ORFs) were predicted in the B1648 strain (5′UTR-1a-1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b-3′UTR). ORFs 4b, 4c and 6b, which have been rarely reported in literature, were present in B1648 and most of the other IBV complete genomes. According to phylogenetic analysis of the full-length genome, replicase transcriptase complex, spike protein, partial S1 gene and M protein, B1648 strain clustered with the non-Massachusetts type strains NGA/A116E7/2006, UKr 27-11, QX-like ITA/90254/2005, QX-like CK/SWE/0658946/10, TN20/00, RF-27/99, RF/06/2007 and SLO/266/05. Based on the partial S1 fragment, B1648 clustered with the strains TN20/00, RF-27/99, RF/06/2007 and SLO/266/05 and, further designated as B1648 genotype. The full-length genome of B1648 shared the highest sequence homology with UKr 27-11, Gray, JMK, and NGA/A116E7/2006 (91.2% to 91.6%) and was least related with the reference Beaudette and Massachusetts strains (89.7%). Nucleotide and amino acid sequence analyses indicated that B1648 strain may have played an important role in the evolution of IBV in Europe and North Africa. Further, the nephropathogenicity determinants might be located on the 1a, spike, M and accessory proteins (3a, 3b, 4b, 4c, 5a, 5b and 6b). Overall, strain B1648 is distinct from all the strains reported so far in Europe and other parts of the world.",2015 Aug 7,"['Reddy, Vishwanatha R.A.P.', 'Theuns, Sebastiaan', 'Roukaerts, Inge D.M.', 'Zeller, Mark', 'Matthijnssens, Jelle', 'Nauwynck, Hans J.']",Viruses,,,True
49335e838ecac21b1628a2aa0877f2d56562a1b7,PMC,Genetic Characterization of the Belgian Nephropathogenic Infectious Bronchitis Virus (NIBV) Reference Strain B1648,http://dx.doi.org/10.3390/v7082827,PMC4576188,26262637,CC BY,"The virulent nephropathogenic infectious bronchitis virus (NIBV) strain B1648 was first isolated in 1984, in Flanders, Belgium. Despite intensive vaccination, B1648 and its variants are still circulating in Europe and North Africa. Here, the full-length genome of this Belgian NIBV reference strain was determined by next generation sequencing (NGS) to understand its evolutionary relationship with other IBV strains, and to identify possible genetic factors that may be associated with the nephropathogenicity. Thirteen open reading frames (ORFs) were predicted in the B1648 strain (5′UTR-1a-1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b-3′UTR). ORFs 4b, 4c and 6b, which have been rarely reported in literature, were present in B1648 and most of the other IBV complete genomes. According to phylogenetic analysis of the full-length genome, replicase transcriptase complex, spike protein, partial S1 gene and M protein, B1648 strain clustered with the non-Massachusetts type strains NGA/A116E7/2006, UKr 27-11, QX-like ITA/90254/2005, QX-like CK/SWE/0658946/10, TN20/00, RF-27/99, RF/06/2007 and SLO/266/05. Based on the partial S1 fragment, B1648 clustered with the strains TN20/00, RF-27/99, RF/06/2007 and SLO/266/05 and, further designated as B1648 genotype. The full-length genome of B1648 shared the highest sequence homology with UKr 27-11, Gray, JMK, and NGA/A116E7/2006 (91.2% to 91.6%) and was least related with the reference Beaudette and Massachusetts strains (89.7%). Nucleotide and amino acid sequence analyses indicated that B1648 strain may have played an important role in the evolution of IBV in Europe and North Africa. Further, the nephropathogenicity determinants might be located on the 1a, spike, M and accessory proteins (3a, 3b, 4b, 4c, 5a, 5b and 6b). Overall, strain B1648 is distinct from all the strains reported so far in Europe and other parts of the world.",2015 Aug 7,"['Reddy, Vishwanatha R.A.P.', 'Theuns, Sebastiaan', 'Roukaerts, Inge D.M.', 'Zeller, Mark', 'Matthijnssens, Jelle', 'Nauwynck, Hans J.']",Viruses,,,False
f793bcacac81ad9341709c9351c6c40c49f4c52e,PMC,eEF1A Interacts with the NS5A Protein and Inhibits the Growth of Classical Swine Fever Virus,http://dx.doi.org/10.3390/v7082833,PMC4576194,26266418,CC BY,"The NS5A protein of classical swine fever virus (CSFV) is involved in the RNA synthesis and viral replication. However, the NS5A-interacting cellular proteins engaged in the CSFV replication are poorly defined. Using yeast two-hybrid screen, the eukaryotic elongation factor 1A (eEF1A) was identified to be an NS5A-binding partner. The NS5A–eEF1A interaction was confirmed by coimmunoprecipitation, glutathione S-transferase (GST) pulldown and laser confocal microscopy assays. The domain I of eEF1A was shown to be critical for the NS5A–eEF1A interaction. Overexpression of eEF1A suppressed the CSFV growth markedly, and conversely, knockdown of eEF1A enhanced the CSFV replication significantly. Furthermore, eEF1A, as well as NS5A, was found to reduce the translation efficiency of the internal ribosome entry site (IRES) of CSFV in a dose-dependent manner, as demonstrated by luciferase reporter assay. Streptavidin pulldown assay revealed that eEF1A could bind to the CSFV IRES. Collectively, our results suggest that eEF1A interacts with NS5A and negatively regulates the growth of CSFV.",2015 Aug 10,"['Li, Su', 'Feng, Shuo', 'Wang, Jing-Han', 'He, Wen-Rui', 'Qin, Hua-Yang', 'Dong, Hong', 'Li, Lian-Feng', 'Yu, Shao-Xiong', 'Li, Yongfeng', 'Qiu, Hua-Ji']",Viruses,,,True
fdc201b99c8f08d1e81622ac71114605c5980a8d,PMC,Vaccine Induced Herd Immunity for Control of Respiratory Syncytial Virus Disease in a Low-Income Country Setting,http://dx.doi.org/10.1371/journal.pone.0138018,PMC4577090,26390032,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is globally ubiquitous, and infection during the first six months of life is a major risk for severe disease and hospital admission; consequently RSV is the most important viral cause of respiratory morbidity and mortality in young children. Development of vaccines for young infants is complicated by the presence of maternal antibodies and immunological immaturity, but vaccines targeted at older children avoid these problems. Vaccine development for young infants has been unsuccessful, but this is not the case for older children (> 6m). Would vaccinating older children have a significant public health impact? We developed a mathematical model to explore the benefits of a vaccine against RSV. METHODS AND FINDINGS: We have used a deterministic age structured model capturing the key epidemiological characteristics of RSV and performed a statistical maximum-likelihood fit to age-specific hospitalization data from a developing country setting. To explore the effects of vaccination under different mixing assumptions, we included two versions of contact matrices: one from a social contact diary study, and the second a synthesised construction based on demographic data. Vaccination is assumed to elicit an immune response equivalent to primary infection. Our results show that immunisation of young children (5–10m) is likely to be a highly effective method of protection of infants (<6m) against hospitalisation. The majority benefit is derived from indirect protection (herd immunity). A full sensitivity and uncertainty analysis using Latin Hypercube Sampling of the parameter space shows that our results are robust to model structure and model parameters. CONCLUSIONS: This result suggests that vaccinating older infants and children against RSV can have a major public health benefit.",2015 Sep 21,"['Kinyanjui, Timothy M.', 'House, Thomas A.', 'Kiti, Moses C.', 'Cane, Patricia A.', 'Nokes, David J.', 'Medley, Graham F.']",PLoS One,,,True
3c568d47a1d134908dc09e454a5a52655d3a9434,PMC,The Acute Chest Syndrome in Cameroonian children living with sickle cell disease,http://dx.doi.org/10.1186/s12887-015-0454-0,PMC4578678,26391669,CC BY,"BACKGROUND: Although sub-Saharan Africa (SSA) is particularly affected by sickle cell disease (SCD), there is dearth of research on this topic in the region, specifically targeting the magnitude of SCD-related complications. We therefore conducted this study to determine the burden of acute chest syndrome (ACS) and describe its clinical and therapeutic aspects among SCD children in Cameroon, a SSA country. METHODS: This was a retrospective study carried-out from September 2013 to June 2014 at the SCD unit of the Mother and Child Centre of the Chantal Biya Foundation, a pediatric reference centre in Yaoundé, Cameroon. We enrolled all SCD children with confirmed diagnosis of ACS, and recorded their clinical presentation at admission along with their evolution during hospitalization. RESULTS: Twenty one cases of ACS were identified during the study period, from 338 hospitalizations of children with SCD. Ages ranged from 11 months to 16 years with a mean (standard deviation) of 5.5 (3.4) years, and a male/female sex ratio of 3.2/1. We noticed relatively low levels of HbF, from 6.4 to 21.9 % with a mean of 14.6 % (6.0 %). The three main symptoms at admission were fever (90.5 %), cough (81 %) and chest pains (28.6 %). Two patients (9.5 %) developed ACS 2 days after admission. The mean values of leukocytes, neutrophils, serum CRP, serum LDH and hemoglobin were respectively 32479.4 (17862.3)/mm(3), 23476 (11543.7)/mm(3), 228.2 (132.6) mg/l, 3452.3 (2916.3) IU/l and 6.5 (1.2) g/dl. The main localizations of radiological alveolar consolidations were the lower lobes (90.5 %). Treatment associated broad-spectrum antibiotics (100 %), hydration (100 %), analgesics (43.2 %), whole blood transfusion (66.7 %), and oxygen supplementation (33.3 %). Blood transfusion significantly improved hemoglobin level (p = 0.039). The duration of hospitalization, the mean of which was 6.8 (3.1) days, was influenced by none of the tested variables (all p values > 0.05). CONCLUSION: ACS is frequent among SCD children in our milieu. Its etiologies seem to be multifactorial. Patients’ parents should be educated to recognize early signs and symptoms of the disease, and consult rapidly. Additionally, clinicians must be trained to diagnose ACS, and manage it promptly and efficiently to avoid its related catastrophic consequences.",2015 Sep 21,"['Nansseu, Jobert Richie N.', 'Alima Yanda, Anastasie Nicole', 'Chelo, David', 'Tatah, Sandra A.', 'Mbassi Awa, Hubert D.', 'Seungue, Judith', 'Koki, Paul Olivier N.']",BMC Pediatr,,,True
76dcc76a0d6041517a4d88f763269bd0196488cb,PMC,"Low prevalence of equine coronavirus in foals in the largest thoroughbred horse breeding region of Japan, 2012–2014",http://dx.doi.org/10.1186/s13028-015-0149-4,PMC4579792,26395082,CC BY,"BACKGROUND: Equine coronavirus (ECoV) is considered to be a diarrheic pathogen in foals. In central Kentucky in the United States, it has been shown that approximately 30 % of thoroughbred foals are infected with ECoV and thus it is considered widely prevalent. In contrast, the epidemiology of ECoV and its relationship to diarrhea in foals are poorly understood in Japan. We investigated ECoV in rectal swabs collected from thoroughbred foals in Japan. RESULTS: We collected 337 rectal swabs from 307 diarrheic foals in the Hidaka district of Hokkaido, the largest thoroughbred horse breeding region in Japan, between 2012 and 2014. In addition, 120 rectal swabs were collected from 120 healthy foals in 2012. These samples were tested by reverse transcription loop-mediated isothermal amplification and a real-time reverse transcription-polymerase chain reaction. All samples collected from diarrheic foals were negative, and only three samples (2.5 %) collected from healthy foals were positive for ECoV. Compared with central Kentucky, ECoV is not prevalent among thoroughbred foals in the Hidaka district of Hokkaido. CONCLUSION: ECoV is not prevalent and was not related to diarrhea in thoroughbred foals in the Hidaka district of Hokkaido between 2012 and 2014.",2015 Sep 22,"['Nemoto, Manabu', 'Oue, Yasuhiro', 'Higuchi, Tohru', 'Kinoshita, Yuta', 'Bannai, Hiroshi', 'Tsujimura, Koji', 'Yamanaka, Takashi', 'Kondo, Takashi']",Acta Vet Scand,,,True
4fe4eefd0cb0263c466d4e7895fcfec52b502a21,PMC,"Knowledge, attitudes, and practices of Hong Kong population towards human A/H7N9 influenza pandemic preparedness, China, 2014",http://dx.doi.org/10.1186/s12889-015-2245-9,PMC4579795,26395243,CC BY,"BACKGROUND: Since SARS epidemic in 2003, Hong Kong has experienced several major epidemic risks, but how general community might react to the repeated infectious diseases health risks have not been studied. In 2013, imported human H7N9 influenza infected cases from China were reported. Our study aims to assess the knowledge, attitude and practice (KAP) concerning A/H7N9 among Hong Kong general population regarding pandemic preparedness in early 2014. METHODS: A cross-sectional, population-based telephone survey study was conducted among the Cantonese-speaking population aged over 15 years in Hong Kong in February 2014. The study survey was composed of 78 KAP questions. Factors associated with individual and household pandemic preparedness were analyzed. RESULTS: Final study sample was 1,020 with a response rate of 45.9 %. Among the respondents, most of them believed personal hygiene and avoidance of avian contacts were effective in preventing H7N9 infections. The majority of respondents had satisfactory hand hygiene practices and avoided touching avian species but did not employ other preventive measures. Female, 25 years old or older, white collar workers, people with chronic diseases and people living in the city center tended to report better hygiene practices. The average State-Trait Anxiety Inventory score was 1.85, similar to that of the period during the first wave and at the start of the second wave of the H7N9 epidemic. Self-reported face masks wearing when having influenza-like illness in general population dropped from 92.4 % during H5N1 period in 2007 to 39.0 % in this study. CONCLUSION: Hong Kong citizens show a low level of anxiety, misconceptions regarding the novel strains as well as gaps between perceived usefulness and practice of preventive measures towards influenza outbreaks. Educational campaigns and framing the issue to increase public and media awareness are crucial in preventing the current public fatigue towards outbreaks.",2015 Sep 22,"['Chan, Emily YY', 'Cheng, Calvin KY', 'Tam, Greta', 'Huang, Zhe', 'Lee, Poyi']",BMC Public Health,,,True
76d6014c9fac61e50caf256e5ca92ea007219c29,PMC,The 15N and 46R Residues of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Nucleocapsid Protein Enhance Regulatory T Lymphocytes Proliferation,http://dx.doi.org/10.1371/journal.pone.0138772,PMC4580451,26397116,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) negatively modulates host immune responses, resulting in persistent infection and immunosuppression. PRRSV infection increases the number of PRRSV-specific regulatory T lymphocytes (Tregs) in infected pigs. However, the target antigens for Tregs proliferation in PRRSV infection have not been fully understood. In this study, we demonstrated that the highly pathogenic PRRSV (HP-PRRSV) induced more CD4(+)CD25(+)Foxp3(+) Tregs than classical PRRSV (C-PRRSV) strain. Of the recombinant GP5, M and N proteins of HP-PRRSV expressed in baculovirus expression systems, only N protein induced Tregs proliferation. The Tregs assays showed that three amino-acid regions, 15–21, 42–48 and 88–94, in N protein played an important role in induction of Tregs proliferation with synthetic peptides covering the whole length of N protein. By using reverse genetic methods, it was firstly found that the 15N and 46R residues in PRRSV N protein were critical for induction of Tregs proliferation. The phenotype of induced Tregs closely resembled that of transforming-growth-factor-β-secreting T helper 3 Tregs in swine. These data should be useful for understanding the mechanism of immunity to PRRSV and development of infection control strategies in the future.",2015 Sep 23,"['Fan, Baochao', 'Liu, Xing', 'Bai, Juan', 'Li, Yufeng', 'Zhang, Qiaoya', 'Jiang, Ping']",PLoS One,,,True
280a11fb6a3cd27873efa93e4600bc4227e7ee0b,PMC,"Communicable Diseases Prioritized According to Their Public Health Relevance, Sweden, 2013",http://dx.doi.org/10.1371/journal.pone.0136353,PMC4580468,26397699,CC BY,"To establish strategic priorities for the Public Health Agency of Sweden we prioritized pathogens according to their public health relevance in Sweden in order to guide resource allocation. We then compared the outcome to ongoing surveillance. We used a modified prioritization method developed at the Robert Koch Institute in Germany. In a Delphi process experts scored pathogens according to ten variables. We ranked the pathogens according to the total score and divided them into four priority groups. We then compared the priority groups to self-reported time spent on surveillance by epidemiologists and ongoing programmes for surveillance through mandatory and/or voluntary notifications and for surveillance of typing results. 106 pathogens were scored. The result of the prioritization process was similar to the outcome of the prioritization in Germany. Common pathogens such as calicivirus and Influenza virus as well as blood-borne pathogens such as human immunodeficiency virus, hepatitis B and C virus, gastro-intestinal infections such as Campylobacter and Salmonella and vector-borne pathogens such as Borrelia were all in the highest priority group. 63% of time spent by epidemiologists on surveillance was spent on pathogens in the highest priority group and all pathogens in the highest priority group, except for Borrelia and varicella-zoster virus, were under surveillance through notifications. Ten pathogens in the highest priority group (Borrelia, calicivirus, Campylobacter, Echinococcus multilocularis, hepatitis C virus, HIV, respiratory syncytial virus, SARS- and MERS coronavirus, tick-borne encephalitis virus and varicella-zoster virus) did not have any surveillance of typing results. We will evaluate the possibilities of surveillance for the pathogens in the highest priority group where we currently do not have any ongoing surveillance and evaluate the need of surveillance for the pathogens from the low priority group where there is ongoing surveillance in order to focus our work on the pathogens with the highest relevance.",2015 Sep 23,"['Dahl, Viktor', 'Tegnell, Anders', 'Wallensten, Anders']",PLoS One,,,True
ee5b43d20a640664510cb7a540caaae4a8e19933,PMC,Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam,http://dx.doi.org/10.1371/journal.pone.0138138,PMC4580613,26398118,CC BY,"Building on a series of ground breaking reviews that first defined and drew attention to emerging infectious diseases (EID), the ‘convergence model’ was proposed to explain the multifactorial causality of disease emergence. The model broadly hypothesizes disease emergence is driven by the co-incidence of genetic, physical environmental, ecological, and social factors. We developed and tested a model of the emergence of highly pathogenic avian influenza (HPAI) H5N1 based on suspected convergence factors that are mainly associated with land-use change. Building on previous geospatial statistical studies that identified natural and human risk factors associated with urbanization, we added new factors to test whether causal mechanisms and pathogenic landscapes could be more specifically identified. Our findings suggest that urbanization spatially combines risk factors to produce particular types of peri-urban landscapes with significantly higher HPAI H5N1 emergence risk. The work highlights that peri-urban areas of Viet Nam have higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture than rural and urban areas. We also found that land-use diversity, a surrogate measure for potential mixing of host populations and other factors that likely influence viral transmission, significantly improves the model’s predictability. Similarly, landscapes where intensive and extensive forms of poultry production overlap were found at greater risk. These results support the convergence hypothesis in general and demonstrate the potential to improve EID prevention and control by combing geospatial monitoring of these factors along with pathogen surveillance programs.",2015 Sep 23,"['Saksena, Sumeet', 'Fox, Jefferson', 'Epprecht, Michael', 'Tran, Chinh C.', 'Nong, Duong H.', 'Spencer, James H.', 'Nguyen, Lam', 'Finucane, Melissa L.', 'Tran, Vien D.', 'Wilcox, Bruce A.']",PLoS One,,,True
73560247ea59c1db0dd80dc9022c7d6795f7d671,PMC,Environmental and Intrinsic Correlates of Stress in Free-Ranging Wolves,http://dx.doi.org/10.1371/journal.pone.0137378,PMC4580640,26398784,CC0,"BACKGROUND: When confronted with a stressor, animals react with several physiological and behavioral responses. Although sustained or repeated stress can result in severe deleterious physiological effects, the causes of stress in free-ranging animals are yet poorly documented. In our study, we aimed at identifying the main factors affecting stress levels in free-ranging wolves (Canis lupus). METHODOLOGY/PRINCIPAL FINDINGS: We used fecal cortisol metabolites (FCM) as an index of stress, after validating the method for its application in wolves. We analyzed a total of 450 fecal samples from eleven wolf packs belonging to three protected populations, in Italy (Abruzzo), France (Mercantour), and the United States (Yellowstone). We collected samples during two consecutive winters in each study area. We found no relationship between FCM concentrations and age, sex or social status of individuals. At the group level, our results suggest that breeding pair permanency and the loss of pack members through processes different from dispersal may importantly impact stress levels in wolves. We measured higher FCM levels in comparatively small packs living in sympatry with a population of free-ranging dogs. Lastly, our results indicate that FCM concentrations are associated with endoparasitic infections of individuals. CONCLUSIONS/SIGNIFICANCE: In social mammals sharing strong bonds among group members, the death of one or several members of the group most likely induces important stress in the remainder of the social unit. The potential impact of social and territorial stability on stress levels should be further investigated in free-ranging populations, especially in highly social and in territorial species. As persistent or repeated stressors may facilitate or induce pathologies and physiological alterations that can affect survival and fitness, we advocate considering the potential impact of anthropogenic causes of stress in management and conservation programs regarding wolves and other wildlife.",2015 Sep 23,"['Molnar, Barbara', 'Fattebert, Julien', 'Palme, Rupert', 'Ciucci, Paolo', 'Betschart, Bruno', 'Smith, Douglas W.', 'Diehl, Peter-Allan']",PLoS One,,,True
1679d2d946adeb59a2ce943f067d4bde57f5577d,PMC,Lack of cross-protection against Mycoplasma haemofelis infection and signs of enhancement in “Candidatus Mycoplasma turicensis”-recovered cats,http://dx.doi.org/10.1186/s13567-015-0240-x,PMC4581119,26403079,CC BY,"“Mycoplasma haemofelis” and “Candidatus Mycoplasma turicensis” are feline hemoplasmas that induce hemolytic anemia. Protection from homologous re-challenge was recently demonstrated in cats recovered from primary infection. Here, we determined if cats recovered from “Cand. M. turicensis” infection were protected against infections with the more pathogenic M. haemofelis. Ten specified pathogen-free cats were exposed to M. haemofelis. Five of the ten cats had recovered from “Cand. M. turicensis” bacteremia (group A), and five cats were naïve controls (group B). No cross-protection was observed. By contrast, the “Cand. M. turicensis”-recovered cats displayed faster M. haemofelis infection onset (earlier PCR-positive and anemic) than the controls. No “Cand. M. turicensis” was detected in any cat. M. haemofelis shedding was observed in saliva, feces and urine. In both groups, evidence of a Th1 response was observed (high IFN-γ, low IL-4), but IL-10 levels were also high. In group A, total, CD4+ and CD8+ T cells increased within days after M. haemofelis exposure. At times of maximal bacteremia, macrocytic hypochromic anemia, neutropenia, monocytosis and a decrease in leukocyte, eosinophil, and lymphocyte counts and subsets thereof (B- and T-cells, CD4+, CD8+ and CD4+CD25+ cells) were particularly significant in group A. Moreover, an increase in protein concentrations, hypoalbuminemia and a polyclonal hypergammaglobulinemia were observed. Five of ten M. haemofelis-infected cats subsequently cleared bacteremia without antibiotic treatment. In conclusion, the study suggests that a previous hemoplasma infection, even when the cat has ostensibly recovered, may influence subsequent infections, lead to an enhancement phenomenon and other differences in infection kinetics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-015-0240-x) contains supplementary material, which is available to authorized users.",2015 Sep 24,"['Baumann, Julia', 'Novacco, Marilisa', 'Willi, Barbara', 'Riond, Barbara', 'Meli, Marina L', 'Boretti, Felicitas S', 'Hofmann-Lehmann, Regina']",Vet Res,,,True
d3871c351aa5020a710d992fe726096265a1b57a,PMC,Binding of SGTA to Rpn13 selectively modulates protein quality control,http://dx.doi.org/10.1242/jcs.165209,PMC4582187,26169395,CC BY,"Rpn13 is an intrinsic ubiquitin receptor of the 26S proteasome regulatory subunit that facilitates substrate capture prior to degradation. Here we show that the C-terminal region of Rpn13 binds to the tetratricopeptide repeat (TPR) domain of SGTA, a cytosolic factor implicated in the quality control of mislocalised membrane proteins (MLPs). The overexpression of SGTA results in a substantial increase in steady-state MLP levels, consistent with an effect on proteasomal degradation. However, this effect is strongly dependent upon the interaction of SGTA with the proteasomal component Rpn13. Hence, overexpression of the SGTA-binding region of Rpn13 or point mutations within the SGTA TPR domain both inhibit SGTA binding to the proteasome and substantially reduce MLP levels. These findings suggest that SGTA can regulate the access of MLPs to the proteolytic core of the proteasome, implying that a protein quality control cycle that involves SGTA and the BAG6 complex can operate at the 19S regulatory particle. We speculate that the binding of SGTA to Rpn13 enables specific polypeptides to escape proteasomal degradation and/or selectively modulates substrate degradation.",2015 Sep 1,"['Leznicki, Pawel', 'Korac-Prlic, Jelena', 'Kliza, Katarzyna', 'Husnjak, Koraljka', 'Nyathi, Yvonne', 'Dikic, Ivan', 'High, Stephen']",J Cell Sci,,,False
9651e34f55c7182fa2aa62a57a94bdbcd31b6f24,PMC,The pro-inflammatory cytokine 14-3-3ε is a ligand of CD13 in cartilage,http://dx.doi.org/10.1242/jcs.169573,PMC4582189,26208633,CC BY,"Osteoarthritis is a whole-joint disease characterized by the progressive destruction of articular cartilage involving abnormal communication between subchondral bone and cartilage. Our team previously identified 14-3-3ε protein as a subchondral bone soluble mediator altering cartilage homeostasis. The aim of this study was to investigate the involvement of CD13 (also known as aminopeptidase N, APN) in the chondrocyte response to 14-3-3ε. After identifying CD13 in chondrocytes, we knocked down CD13 with small interfering RNA (siRNA) and blocking antibodies in articular chondrocytes. 14-3-3ε-induced MMP-3 and MMP-13 was significantly reduced with CD13 knockdown, which suggests that it has a crucial role in 14-3-3ε signal transduction. Aminopeptidase N activity was identified in chondrocytes, but the activity was unchanged after stimulation with 14-3-3ε. Direct interaction between CD13 and 14-3-3ε was then demonstrated by surface plasmon resonance. Using labeled 14-3-3ε, we also found that 14-3-3ε binds to the surface of chondrocytes in a manner that is dependent on CD13. Taken together, these results suggest that 14-3-3ε might directly bind to CD13, which transmits its signal in chondrocytes to induce a catabolic phenotype similar to that observed in osteoarthritis. The 14-3-3ε–CD13 interaction could be a new therapeutic target in osteoarthritis.",2015 Sep 1,"['Nefla, Meriam', 'Sudre, Laure', 'Denat, Guillaume', 'Priam, Sabrina', 'Andre-Leroux, Gwenaëlle', 'Berenbaum, Francis', 'Jacques, Claire']",J Cell Sci,,,False
a969190e8cae42cb65e639aee83d71d9f78c4dc0,PMC,Determination of the infectious titer and virulence of an original US porcine epidemic diarrhea virus PC22A strain,http://dx.doi.org/10.1186/s13567-015-0249-1,PMC4582625,26408019,CC BY,"The infectious dose of a virus pool of original US PEDV strain PC22A was determined in 4-day-old, cesarean-derived, colostrum-deprived (CDCD) piglets. The median pig diarrhea dose (PDD(50)) of the virus pool was determined as 7.35 log(10) PDD(50)/mL, similar to the cell culture infectious titer, 7.75 log(10) plaque-forming units (PFU)/mL. 100 PDD(50) caused watery diarrhea in all conventional suckling piglets (n = 12) derived from a PEDV-naive sow, whereas 1000 and 10 000 PDD(50) did not cause diarrhea in piglets derived from two PEDV-field exposed-recovered sows. This information is important for future PEDV challenge studies and validation of PEDV vaccines.",2015 Sep 25,"['Liu, Xinsheng', 'Lin, Chun-Ming', 'Annamalai, Thavamathi', 'Gao, Xiang', 'Lu, Zhongyan', 'Esseili, Malak A', 'Jung, Kwonil', 'El-Tholoth, Mohamed', 'Saif, Linda J', 'Wang, Qiuhong']",Vet Res,,,True
24f4f393fb59daab089844e7af64e913d2951034,PMC,The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes,http://dx.doi.org/10.1371/journal.pone.0138075,PMC4583277,26406906,CC BY,"Pelargonium sidoides is a medical herb and respective extracts are used very frequently for the treatment of respiratory tract infections. However, the effects of Pelargonium sidoides and a special extract prepared from its roots (EPs 7630) on human immune cells are not fully understood. Here we demonstrate that EPs 7630 induced a rapid and dose-dependent production of TNF-α, IL-6, and IL-10 by human blood immune cells. This EPs 7630-induced cytokine profile was more pro-inflammatory in comparison with the profile induced by viral or bacterial infection-mimicking agents. The search for EPs 7630 target cells revealed that T-cells did not respond to EPs 7630 stimulation by production of TNF-α, IL-6, or IL-10. Furthermore, pretreatment of T-cells with EPs 7630 did not modulate their TNF-α, IL-6, and IL-10 secretion during subsequent activation. In contrast to lymphocytes, monocytes showed clear intracellular TNF-α staining after EPs 7630 treatment. Accordingly, EPs 7630 predominantly provoked activation of MAP kinases and inhibition of p38 strongly reduced the monocyte TNF-α production. The pretreatment of blood immune cells with EPs 7630 lowered their secretion of TNF-α and IL-10 and caused an IL-6 dominant response during second stimulation with viral or bacterial infection-mimicking agents. In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase protein production in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells.",2015 Sep 25,"['Witte, Katrin', 'Koch, Egon', 'Volk, Hans-Dieter', 'Wolk, Kerstin', 'Sabat, Robert']",PLoS One,,,True
dccf40912c6da39a0326cd025ae83d3933a1849a,PMC,New Epidemiological and Clinical Signatures of 18 Pathogens from Respiratory Tract Infections Based on a 5-Year Study,http://dx.doi.org/10.1371/journal.pone.0138684,PMC4583381,26406339,CC BY,"BACKGROUND: Respiratory tract infections (RTIs) are a heavy burden on society. However, due to the complex etiology of RTIs, the clinical diagnosis, treatment, and prevention of these infections remain challenging, especially in developing countries. METHODS: To determine the epidemiological and clinical characteristics of 18 respiratory pathogens, we analyzed 12,502 patients with acute respiratory infections (ARIs) by performing polymerase chain reaction (PCR) on patient pharyngeal swabs. RESULTS: Samples positive for at least 1 pathogen were obtained from 48.42% of the total patients. Of these pathogen-positive patients, 17.99% were infected with more than 1 pathogen. Of the 18 pathogens analyzed, four were detected with a positive detection rate (PDR) > 5%: influenza A virus (IAV) > respiratory syncytial virus (RSV) >Mycoplasma pneumoniae (MP) > human coronavirus (HCoV). The pathogens with the 4 highest co-infection rates (CIRs) were as follows: HCoV > human bocavirus (HBoV) > enterovirus (EV) > parainfluenza virus (PIV). The overall positive detection rate (PDR) varied significantly according to patient age, the season and year of detection, and the disease subgroup, but not according to patient sex. The individual PDRs of the pathogens followed 3 types of distributions for patient sex, 4 types of distributions for patient age, 4 types of seasonal distributions, 2 types of seasonal epidemic trends, 4 types of yearly epidemic trends, and different susceptibility distributions in the disease subgroups. Additionally, the overall CIR showed significantly different distributions according to patient sex, patient age, and the disease subgroup, whereas the CIRs of individual pathogens suggested significant preference characteristics. CONCLUSION: IAV remains the most common pathogen among the pathogens analyzed. More effort should be directed toward the prevention and control of pathogens that show a trend of increasing incidence such as HCoV, human adenovirus (ADV), and RSV. Although clinically distinguishing specific pathogens responsible for RTIs is difficult, the epidemiological and clinical characteristics of the various RTI-causing agents could provide clues for clinicians, thereby informing decisions regarding prevention and medication and guiding appropriate public health strategies.",2015 Sep 25,"['Liao, Xiaohong', 'Hu, Zhengbo', 'Liu, Wenkuan', 'Lu, Yan', 'Chen, Dehui', 'Chen, Meixin', 'Qiu, Shuyan', 'Zeng, Zhiqi', 'Tian, Xingui', 'Cui, Hong', 'Zhou, Rong']",PLoS One,,,True
a5360f18c21cf7f9a04e9b21663301b4548eadd9,PMC,A Multiple siRNA-Based Anti-HIV/SHIV Microbicide Shows Protection in Both In Vitro and In Vivo Models,http://dx.doi.org/10.1371/journal.pone.0135288,PMC4583459,26407080,CC0,"Human immunodeficiency virus (HIV) types 1 and 2 (HIV-1 and HIV-2) are the etiologic agents of AIDS. Most HIV-1 infected individuals worldwide are women, who acquire HIV infections during sexual contact. Blocking HIV mucosal transmission and local spread in the female lower genital tract is important in preventing infection and ultimately eliminating the pandemic. Microbicides work by destroying the microbes or preventing them from establishing an infection. Thus, a number of different types of microbicides are under investigation, however, the lack of their solubility and bioavailability, and toxicity has been major hurdles. Herein, we report the development of multifunctional chitosan-lipid nanocomplexes that can effectively deliver plasmids encoding siRNA(s) as microbicides without adverse effects and provide significant protection against HIV in both in vitro and in vivo models. Chitosan or chitosan-lipid (chlipid) was complexed with a cocktail of plasmids encoding HIV-1-specific siRNAs (psiRNAs) and evaluated for their efficacy in HEK-293 cells, PBMCs derived from nonhuman primates, 3-dimensional human vaginal ectocervical tissue (3D-VEC) model and also in non-human primate model. Moreover, prophylactic administration of the chlipid to deliver a psiRNA cocktail intravaginally with a cream formulation in a non-human primate model showed substantial reduction of SHIV (simian/human immunodeficiency virus SF162) viral titers. Taken together, these studies demonstrate the potential of chlipid-siRNA nanocomplexes as a potential genetic microbicide against HIV infections.",2015 Sep 25,"['Boyapalle, Sandhya', 'Xu, Weidong', 'Raulji, Payal', 'Mohapatra, Subhra', 'Mohapatra, Shyam S']",PLoS One,,,True
8feaa6f0bac0c30c9b3cf6634082e8923d99b070,PMC,Modulation of the Host Lipid Landscape to Promote RNA Virus Replication: The Picornavirus Encephalomyocarditis Virus Converges on the Pathway Used by Hepatitis C Virus,http://dx.doi.org/10.1371/journal.ppat.1005185,PMC4583462,26406250,CC BY,"Cardioviruses, including encephalomyocarditis virus (EMCV) and the human Saffold virus, are small non-enveloped viruses belonging to the Picornaviridae, a large family of positive-sense RNA [(+)RNA] viruses. All (+)RNA viruses remodel intracellular membranes into unique structures for viral genome replication. Accumulating evidence suggests that picornaviruses from different genera use different strategies to generate viral replication organelles (ROs). For instance, enteroviruses (e.g. poliovirus, coxsackievirus, rhinovirus) rely on the Golgi-localized phosphatidylinositol 4-kinase III beta (PI4KB), while cardioviruses replicate independently of the kinase. By which mechanisms cardioviruses develop their ROs is currently unknown. Here we show that cardioviruses manipulate another PI4K, namely the ER-localized phosphatidylinositol 4-kinase III alpha (PI4KA), to generate PI4P-enriched ROs. By siRNA-mediated knockdown and pharmacological inhibition, we demonstrate that PI4KA is an essential host factor for EMCV genome replication. We reveal that the EMCV nonstructural protein 3A interacts with and is responsible for PI4KA recruitment to viral ROs. The ensuing phosphatidylinositol 4-phosphate (PI4P) proved important for the recruitment of oxysterol-binding protein (OSBP), which delivers cholesterol to EMCV ROs in a PI4P-dependent manner. PI4P lipids and cholesterol are shown to be required for the global organization of the ROs and for viral genome replication. Consistently, inhibition of OSBP expression or function efficiently blocked EMCV RNA replication. In conclusion, we describe for the first time a cellular pathway involved in the biogenesis of cardiovirus ROs. Remarkably, the same pathway was reported to promote formation of the replication sites of hepatitis C virus, a member of the Flaviviridae family, but not other picornaviruses or flaviviruses. Thus, our results highlight the convergent recruitment by distantly related (+)RNA viruses of a host lipid-modifying pathway underlying formation of viral replication sites.",2015 Sep 25,"['Dorobantu, Cristina M.', 'Albulescu, Lucian', 'Harak, Christian', 'Feng, Qian', 'van Kampen, Mirjam', 'Strating, Jeroen R. P. M.', 'Gorbalenya, Alexander E.', 'Lohmann, Volker', 'van der Schaar, Hilde M.', 'van Kuppeveld, Frank J. M.']",PLoS Pathog,,,True
daeba3efafc5b3f9e71e38069aadf1e0178bac9d,PMC,Challenges of the Unknown: Clinical Application of Microbial Metagenomics,http://dx.doi.org/10.1155/2015/292950,PMC4584244,26451363,CC BY,"Availability of fast, high throughput and low cost whole genome sequencing holds great promise within public health microbiology, with applications ranging from outbreak detection and tracking transmission events to understanding the role played by microbial communities in health and disease. Within clinical metagenomics, identifying microorganisms from a complex and host enriched background remains a central computational challenge. As proof of principle, we sequenced two metagenomic samples, a known viral mixture of 25 human pathogens and an unknown complex biological model using benchtop technology. The datasets were then analysed using a bioinformatic pipeline developed around recent fast classification methods. A targeted approach was able to detect 20 of the viruses against a background of host contamination from multiple sources and bacterial contamination. An alternative untargeted identification method was highly correlated with these classifications, and over 1,600 species were identified when applied to the complex biological model, including several species captured at over 50% genome coverage. In summary, this study demonstrates the great potential of applying metagenomics within the clinical laboratory setting and that this can be achieved using infrastructure available to nondedicated sequencing centres.",2015 Sep 14,"['Rose, Graham', 'Wooldridge, David J.', 'Anscombe, Catherine', 'Mee, Edward T.', 'Misra, Raju V.', 'Gharbia, Saheer']",Int J Genomics,,,True
4d2e434006533cb3bbb701dffb53169b40a9c315,PMC,Viral Mimicry to Usurp Ubiquitin and SUMO Host Pathways,http://dx.doi.org/10.3390/v7092849,PMC4584293,26343706,CC BY,"Posttranslational modifications (PTMs) of proteins include enzymatic changes by covalent addition of cellular regulatory determinants such as ubiquitin (Ub) and small ubiquitin-like modifier (SUMO) moieties. These modifications are widely used by eukaryotic cells to control the functional repertoire of proteins. Over the last decade, it became apparent that the repertoire of ubiquitiylation and SUMOylation regulating various biological functions is not restricted to eukaryotic cells, but is also a feature of human virus families, used to extensively exploit complex host-cell networks and homeostasis. Intriguingly, besides binding to host SUMO/Ub control proteins and interfering with the respective enzymatic cascade, many viral proteins mimic key regulatory factors to usurp this host machinery and promote efficient viral outcomes. Advanced detection methods and functional studies of ubiquitiylation and SUMOylation during virus-host interplay have revealed that human viruses have evolved a large arsenal of strategies to exploit these specific PTM processes. In this review, we highlight the known viral analogs orchestrating ubiquitin and SUMO conjugation events to subvert and utilize basic enzymatic pathways.",2015 Aug 28,"['Wimmer, Peter', 'Schreiner, Sabrina']",Viruses,,,True
608a7194b225bedf27e124dfbe8f2acecbca587f,PMC,"Exosome Biogenesis, Regulation, and Function in Viral Infection",http://dx.doi.org/10.3390/v7092862,PMC4584306,26393640,CC BY,"Exosomes are extracellular vesicles released upon fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. They originate as intraluminal vesicles (ILVs) during the process of MVB formation. Exosomes were shown to contain selectively sorted functional proteins, lipids, and RNAs, mediating cell-to-cell communications and hence playing a role in the physiology of the healthy and diseased organism. Challenges in the field include the identification of mechanisms sustaining packaging of membrane-bound and soluble material to these vesicles and the understanding of the underlying processes directing MVBs for degradation or fusion with the plasma membrane. The investigation into the formation and roles of exosomes in viral infection is in its early years. Although still controversial, exosomes can, in principle, incorporate any functional factor, provided they have an appropriate sorting signal, and thus are prone to viral exploitation. This review initially focuses on the composition and biogenesis of exosomes. It then explores the regulatory mechanisms underlying their biogenesis. Exosomes are part of the endocytic system, which is tightly regulated and able to respond to several stimuli that lead to alterations in the composition of its sub-compartments. We discuss the current knowledge of how these changes affect exosomal release. We then summarize how different viruses exploit specific proteins of endocytic sub-compartments and speculate that it could interfere with exosome function, although no direct link between viral usage of the endocytic system and exosome release has yet been reported. Many recent reports have ascribed functions to exosomes released from cells infected with a variety of animal viruses, including viral spread, host immunity, and manipulation of the microenvironment, which are discussed. Given the ever-growing roles and importance of exosomes in viral infections, understanding what regulates their composition and levels, and defining their functions will ultimately provide additional insights into the virulence and persistence of infections.",2015 Sep 17,"['Alenquer, Marta', 'Amorim, Maria João']",Viruses,,,True
48c20fe82a21edeefb8e1966189db32213a446fc,PMC,Tight Junctions Go Viral!,http://dx.doi.org/10.3390/v7092865,PMC4584309,26404354,CC BY,"Tight junctions (TJs) are highly specialized membrane domains involved in many important cellular processes such as the regulation of the passage of ions and macromolecules across the paracellular space and the establishment of cell polarity in epithelial cells. Over the past few years there has been increasing evidence that different components of the TJs can be hijacked by viruses in order to complete their infectious cycle. Viruses from at least nine different families of DNA and RNA viruses have been reported to use TJ proteins in their benefit. For example, TJ proteins such as JAM-A or some members of the claudin family of proteins are used by members of the Reoviridae family and hepatitis C virus as receptors or co-receptors during their entry into their host cells. Reovirus, in addition, takes advantage of the TJ protein Junction Adhesion Molecule-A (JAM-A) to achieve its hematogenous dissemination. Some other viruses are capable of regulating the expression or the localization of TJ proteins to induce cell transformation or to improve the efficiency of their exit process. This review encompasses the importance of TJs for viral entry, replication, dissemination, and egress, and makes a clear statement of the importance of studying these proteins to gain a better understanding of the replication strategies used by viruses that infect epithelial and/or endothelial cells.",2015 Sep 23,"['Torres-Flores, Jesús M.', 'Arias, Carlos F.']",Viruses,,,True
f057fa2845067210cbd31e79d8a83cdff0aa96f1,PMC,Interferon lambda inhibits dengue virus replication in epithelial cells,http://dx.doi.org/10.1186/s12985-015-0383-4,PMC4584467,26411318,CC BY,"BACKGROUND: In viral disease, infection is controlled at the cellular level by type I interferon (IFN-I), but dengue virus (DENV) has the ability to inhibit this response. Type III interferon, also known as lambda IFN (IFN-III or IFN-λ), is a complementary pathway to the antiviral response by IFN-I. This work analyzed the IFN-λ (IFN-III) mediated antiviral response against DENV serotype 2 (DENV-2) infection. METHODS: Dengue fever patients were sampled to determine their IFN-λ levels by ELISA. To study the IFN-λ response during DENV infection we selected the epithelial cell line C33-A, and we demonstrated that it is permissive to DENV-2 infection. The effect of IFN-λ on virus replication was determined in these cells, in parallel to the expression of IFN-stimulated genes (ISGs), and Suppressor of Cytokine Signaling (SOCS), genes measured by RT-qPCR. RESULTS: We found increased (~1.8 times) serological IFN-λ in dengue fever patients compared to healthy blood donors. IFN-λ inhibited DENV-2 replication in a dose-dependent manner in vitro. The reduction of viral titer corresponded with increased ISG mRNA levels (MX1 and OAS1), with the highest inhibition occurring at ISG’s peak expression. Presence of IFN-negative regulators, SOCS1 and SOCS3, during DENV-2 infection was associated with reduced IFN-λ1 expression. CONCLUSIONS: Evidence described here suggests that IFN-λ is a good candidate inhibitor of viral replication in dengue infection. Mechanisms for the cellular and organismal interplay between DENV and IFN- λ need to be further studied as they could provide insights into strategies to treat this disease. Furthermore, we report a novel epithelial model to study dengue infection in vitro.",2015 Sep 28,"['Palma-Ocampo, Helen K.', 'Flores-Alonso, Juan C.', 'Vallejo-Ruiz, Verónica', 'Reyes-Leyva, Julio', 'Flores-Mendoza, Lilian', 'Herrera-Camacho, Irma', 'Rosas-Murrieta, Nora H.', 'Santos-López, Gerardo']",Virol J,,,True
3d0d60d3d1906b4086ca3e10bcf5dde7b4db69b8,PMC,Disruptive Innovation Can Prevent the Next Pandemic,http://dx.doi.org/10.3389/fpubh.2015.00215,PMC4585064,26442242,CC BY,"Public health surveillance (PHS) is at a tipping point, where the application of novel processes, technologies, and tools promise to vastly improve efficiency and effectiveness. Yet twentieth century, entrenched ideology and lack of training results in slow uptake and resistance to change. The term disruptive innovation – used to describe advances in technology and processes that change existing markets – is useful to describe the transformation of PHS. Past disruptive innovations used in PHS, such as distance learning, the smart phone, and field-based laboratory testing have outpaced older services, practices, and technologies used in the traditional classroom, governmental offices, and personal communication, respectively. Arguably, the greatest of these is the Internet – an infrastructural innovation that continues to enable exponential benefits in seemingly limitless ways. Considering the Global Health Security Agenda and facing emerging and reemerging infectious disease threats, evolving environmental and behavioral risks, and ever changing epidemiologic trends, PHS must transform. Embracing disruptive innovation in the structures and processes of PHS can be unpredictable. However, it is necessary to strengthen and unlock the potential to prevent, detect, and respond.",2015 Sep 23,"['Shaikh, Affan T.', 'Ferland, Lisa', 'Hood-Cree, Robert', 'Shaffer, Loren', 'McNabb, Scott J. N.']",Front Public Health,,,True
595582a254c921f28d7c5cb9cb42e1dcabff7108,PMC,"Rapid detection of Acinetobacter baumannii and molecular epidemiology of carbapenem-resistant A. baumannii in two comprehensive hospitals of Beijing, China",http://dx.doi.org/10.3389/fmicb.2015.00997,PMC4585070,26441924,CC BY,"Acinetobacter baumannii is an important opportunistic pathogen associated with a variety of nosocomial infections. A rapid and sensitive molecular detection in clinical isolates is quite needed for the appropriate therapy and outbreak control of A. baumannii. Group 2 carbapenems have been considered the agents of choice for the treatment of multiple drug-resistant A. baumannii. But the prevalence of carbapenem-resistant A. baumannii (CRAB) has been steadily increasing in recent years. Here, we developed a loop-mediated isothermal amplification (LAMP) assay for the rapid detection of A. baumannii in clinical samples by using high-specificity primers of the bla(OXA-51) gene. Then we investigated the OXA-carbapenemases molecular epidemiology of A. baumannii isolates in two comprehensive hospitals in Beijing. The results showed that the LAMP assay could detect target DNA within 60 min at 65°C. The detection limit was 50 pg/μl, which was about 10-fold greater than that of PCR. Furthermore, this method could distinguish A. baumannii from the homologous A. nosocomialis and A. pittii. A total of 228 positive isolates were identified by this LAMP-based method for A. baumannii from 335 intensive care unit patients with clinically suspected multi-resistant infections in two hospitals in Beijing. The rates of CRAB are on the rise and are slowly becoming a routine phenotype for A. baumannii. Among the CRABs, 92.3% harbored both the bla(OXA-23) and bla(OXA-51) genes. Thirty-three pulsotypes were identified by pulsed-field gel electrophoresis, and the majority belonged to clone C. In conclusion, the LAMP method developed for detecting A. baumannii was faster and simpler than conventional PCR and has great potential for both point-of-care testing and basic research. We further demonstrated a high distribution of class D carbapenemase-encoding genes, mainly OXA-23, which presents an emerging threat in hospitals in China.",2015 Sep 23,"['Li, Puyuan', 'Niu, Wenkai', 'Li, Huan', 'Lei, Hong', 'Liu, Wei', 'Zhao, Xiangna', 'Guo, Leijing', 'Zou, Dayang', 'Yuan, Xin', 'Liu, Huiying', 'Yuan, Jing', 'Bai, Changqing']",Front Microbiol,,,True
7110b46076a08c546102c3501ab5220f96e78708,PMC,Dipeptidyl Peptidase-4 Regulation of SDF-1/CXCR4 Axis: Implications for Cardiovascular Disease,http://dx.doi.org/10.3389/fimmu.2015.00477,PMC4585326,26441982,CC BY,"Dipeptidyl peptidase-4 (DPP4) is a ubiquitously expressed protease that regulates diverse number of physiological functions. As a dipeptidase, it exerts its catalytic effects on proteins/peptides with proline, alanine, or serine in the penultimate (P1) amino acid residue from the amino terminus. The evidence to date supports an important effect of DPP4 in catalytic cleavage of incretin peptides and this perhaps represents the main mechanism by which DPP4 inhibition improves glycemic control. DPP4 also plays an important role in the degradation of multiple chemokines of which stromal cell-derived factor-1 (SDF-1, also known as CXCL12) is perhaps an increasingly recognized target, given its importance in processes, such as hematopoiesis, angiogenesis, and stem cell homing. In the current review, we will summarize the importance of DPP4-mediated enzymatic processing of cytokines/chemokines with an emphasis on SDF-1 and resultant implications for cardiovascular physiology and disease.",2015 Sep 25,"['Zhong, Jixin', 'Rajagopalan, Sanjay']",Front Immunol,,,True
7e73ff88b8e995535a2783a7ba78a743afd557a8,PMC,The heptad repeat region is a major selection target in MERS-CoV and related coronaviruses,http://dx.doi.org/10.1038/srep14480,PMC4585914,26404138,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) originated in bats and spread to humans via zoonotic transmission from camels. We analyzed the evolution of the spike (S) gene in betacoronaviruses (betaCoVs) isolated from different mammals, in bat coronavirus populations, as well as in MERS-CoV strains from the current outbreak. Results indicated several positively selected sites located in the region comprising the two heptad repeats (HR1 and HR2) and their linker. Two sites (R652 and V1060) were positively selected in the betaCoVs phylogeny and correspond to mutations associated with expanded host range in other coronaviruses. During the most recent evolution of MERS-CoV, adaptive mutations in the HR1 (Q/R/H1020) arose in camels or in a previous host and spread to humans. We determined that different residues at position 1020 establish distinct inter- and intra-helical interactions and affect the stability of the six-helix bundle formed by the HRs. A similar effect on stability was observed for a nearby mutation (T1015N) that increases MERS-CoV infection efficiency in vitro. Data herein indicate that the heptad repeat region was a major target of adaptive evolution in MERS-CoV-related viruses; these results are relevant for the design of fusion inhibitor peptides with antiviral function.",2015 Sep 25,"['Forni, Diego', 'Filippi, Giulia', 'Cagliani, Rachele', 'De Gioia, Luca', 'Pozzoli, Uberto', 'Al-Daghri, Nasser', 'Clerici, Mario', 'Sironi, Manuela']",Sci Rep,,,True
700dd02a9da7cdbddb49e21feafe8dad7985a7a3,PMC,The heptad repeat region is a major selection target in MERS-CoV and related coronaviruses,http://dx.doi.org/10.1038/srep14480,PMC4585914,26404138,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) originated in bats and spread to humans via zoonotic transmission from camels. We analyzed the evolution of the spike (S) gene in betacoronaviruses (betaCoVs) isolated from different mammals, in bat coronavirus populations, as well as in MERS-CoV strains from the current outbreak. Results indicated several positively selected sites located in the region comprising the two heptad repeats (HR1 and HR2) and their linker. Two sites (R652 and V1060) were positively selected in the betaCoVs phylogeny and correspond to mutations associated with expanded host range in other coronaviruses. During the most recent evolution of MERS-CoV, adaptive mutations in the HR1 (Q/R/H1020) arose in camels or in a previous host and spread to humans. We determined that different residues at position 1020 establish distinct inter- and intra-helical interactions and affect the stability of the six-helix bundle formed by the HRs. A similar effect on stability was observed for a nearby mutation (T1015N) that increases MERS-CoV infection efficiency in vitro. Data herein indicate that the heptad repeat region was a major target of adaptive evolution in MERS-CoV-related viruses; these results are relevant for the design of fusion inhibitor peptides with antiviral function.",2015 Sep 25,"['Forni, Diego', 'Filippi, Giulia', 'Cagliani, Rachele', 'De Gioia, Luca', 'Pozzoli, Uberto', 'Al-Daghri, Nasser', 'Clerici, Mario', 'Sironi, Manuela']",Sci Rep,,,False
bd1d9c526a0194d356d7a65ebcebc322dd872a36,PMC,Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg?,http://dx.doi.org/10.3390/nu7095350,PMC4586545,26371035,CC BY,"In the present narrative review, we analyzed the relationship between seronegative celiac disease (SNCD) and immunoglobulin deficiencies. For this purpose, we conducted a literature search on the main medical databases. SNCD poses a diagnostic dilemma. Villous blunting, intraepithelial lymphocytes (IELs) count and gluten “challenge” are the most reliable markers. Immunohistochemistry/immunofluorescence tissue transglutaminase (tTG)-targeted mucosal immunoglobulin A (IgA) immune complexes in the intestinal mucosa of SNCD patients may be useful. In our experience, tTG-mRNA was similarly increased in seropositive celiac disease (CD) and suspected SNCD, and strongly correlated with the IELs count. This increase is found even in the IELs’ range of 15–25/100 enterocytes, suggesting that there may be a “grey zone” of gluten-related disorders. An immune deregulation (severely lacking B-cell differentiation) underlies the association of SNCD with immunoglobulin deficiencies. Therefore, CD may be linked to autoimmune disorders and immune deficits (common variable immunodeficiency (CVID)/IgA selective deficiency). CVID is a heterogeneous group of antibodies dysfunction, whose association with CD is demonstrated only by the response to a gluten-free diet (GFD). We hypothesized a familial inheritance between CD and CVID. Selective IgA deficiency, commonly associated with CD, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD) is rare (<300 cases) and associated to CD in 5% of cases. We diagnosed SNCD in a patient affected by sIgMD using the tTG-mRNA assay. One-year GFD induced IgM restoration. This evidence, supporting a link between SNCD and immunoglobulin deficiencies, suggests that we should take a closer look at this association.",2015 Sep 8,"['Giorgio, Floriana', 'Principi, Mariabeatrice', 'Losurdo, Giuseppe', 'Piscitelli, Domenico', 'Iannone, Andrea', 'Barone, Michele', 'Amoruso, Annacinzia', 'Ierardi, Enzo', 'Di Leo, Alfredo']",Nutrients,,,True
3ceddc72c46d0c69ff2718e3780a0d987da91cab,PMC,"Infectious Diseases, Urbanization and Climate Change: Challenges in Future China",http://dx.doi.org/10.3390/ijerph120911025,PMC4586659,26371017,CC BY,"China is one of the largest countries in the world with nearly 20% of the world’s population. There have been significant improvements in economy, education and technology over the last three decades. Due to substantial investments from all levels of government, the public health system in China has been improved since the 2003 severe acute respiratory syndrome (SARS) outbreak. However, infectious diseases still remain a major population health issue and this may be exacerbated by rapid urbanization and unprecedented impacts of climate change. This commentary aims to explore China’s current capacity to manage infectious diseases which impair population health. It discusses the existing disease surveillance system and underscores the critical importance of strengthening the system. It also explores how the growing migrant population, dramatic changes in the natural landscape following rapid urbanization, and changing climatic conditions can contribute to the emergence and re-emergence of infectious disease. Continuing research on infectious diseases, urbanization and climate change may inform the country’s capacity to deal with emerging and re-emerging infectious diseases in the future.",2015 Sep 7,"['Tong, Michael Xiaoliang', 'Hansen, Alana', 'Hanson-Easey, Scott', 'Cameron, Scott', 'Xiang, Jianjun', 'Liu, Qiyong', 'Sun, Yehuan', 'Weinstein, Philip', 'Han, Gil-Soo', 'Williams, Craig', 'Bi, Peng']",Int J Environ Res Public Health,,,True
aaf76d77eb09c00e78926e76d0e9644a3d472161,PMC,Model Selection and Evaluation Based on Emerging Infectious Disease Data Sets including A/H1N1 and Ebola,http://dx.doi.org/10.1155/2015/207105,PMC4586906,26451161,CC BY,"The aim of the present study is to apply simple ODE models in the area of modeling the spread of emerging infectious diseases and show the importance of model selection in estimating parameters, the basic reproduction number, turning point, and final size. To quantify the plausibility of each model, given the data and the set of four models including Logistic, Gompertz, Rosenzweg, and Richards models, the Bayes factors are calculated and the precise estimates of the best fitted model parameters and key epidemic characteristics have been obtained. In particular, for Ebola the basic reproduction numbers are 1.3522 (95% CI (1.3506, 1.3537)), 1.2101 (95% CI (1.2084, 1.2119)), 3.0234 (95% CI (2.6063, 3.4881)), and 1.9018 (95% CI (1.8565, 1.9478)), the turning points are November 7,November 17, October 2, and November 3, 2014, and the final sizes until December 2015 are 25794 (95% CI (25630, 25958)), 3916 (95% CI (3865, 3967)), 9886 (95% CI (9740, 10031)), and 12633 (95% CI (12515, 12750)) for West Africa, Guinea, Liberia, and Sierra Leone, respectively. The main results confirm that model selection is crucial in evaluating and predicting the important quantities describing the emerging infectious diseases, and arbitrarily picking a model without any consideration of alternatives is problematic.",2015 Sep 15,"['Liu, Wendi', 'Tang, Sanyi', 'Xiao, Yanni']",Comput Math Methods Med,,,True
4bdb53b23deb0bc56d0aa7b26551ab76b1fd082e,PMC,"Real-time characterization of risks of death associated with the Middle East respiratory syndrome (MERS) in the Republic of Korea, 2015",http://dx.doi.org/10.1186/s12916-015-0468-3,PMC4588253,26420593,CC BY,"BACKGROUND: An outbreak of the Middle East respiratory syndrome (MERS), comprising 185 cases linked to healthcare facilities, occurred in the Republic of Korea from May to July 2015. Owing to the nosocomial nature of the outbreak, it is particularly important to gain a better understanding of the epidemiological determinants characterizing the risk of MERS death in order to predict the heterogeneous risk of death in medical settings. METHODS: We have devised a novel statistical model that identifies the risk of MERS death during the outbreak in real time. While accounting for the time delay from illness onset to death, risk factors for death were identified using a linear predictor tied to a logit model. We employ this approach to (1) quantify the risks of death and (2) characterize the temporal evolution of the case fatality ratio (CFR) as case ascertainment greatly improved during the course of the outbreak. RESULTS: Senior persons aged 60 years or over were found to be 9.3 times (95 % confidence interval (CI), 5.3–16.9) more likely to die compared to younger MERS cases. Patients under treatment were at a 7.8-fold (95 % CI, 4.0–16.7) significantly higher risk of death compared to other MERS cases. The CFR among patients aged 60 years or older under treatment was estimated at 48.2 % (95 % CI, 35.2–61.3) as of July 31, 2015, while the CFR among other cases was estimated to lie below 15 %. From June 6, 2015, onwards, the CFR declined 0.3-fold (95 % CI, 0.1–1.1) compared to the earlier epidemic period, which may perhaps reflect enhanced case ascertainment following major contact tracing efforts. CONCLUSIONS: The risk of MERS death was significantly associated with older age as well as treatment for underlying diseases after explicitly adjusting for the delay between illness onset and death. Because MERS outbreaks are greatly amplified in the healthcare setting, enhanced infection control practices in medical facilities should strive to shield risk groups from MERS exposure.",2015 Sep 30,"['Mizumoto, Kenji', 'Endo, Akira', 'Chowell, Gerardo', 'Miyamatsu, Yuichiro', 'Saitoh, Masaya', 'Nishiura, Hiroshi']",BMC Med,,,True
a9075cf8e6853657941c799058d329b3e386fecd,PMC,Recovering full-length viral genomes from metagenomes,http://dx.doi.org/10.3389/fmicb.2015.01069,PMC4589665,26483782,CC BY,"Infectious disease metagenomics is driven by the question: “what is causing the disease?” in contrast to classical metagenome studies which are guided by “what is out there?” In case of a novel virus, a first step to eventually establishing etiology can be to recover a full-length viral genome from a metagenomic sample. However, retrieval of a full-length genome of a divergent virus is technically challenging and can be time-consuming and costly. Here we discuss different assembly and fragment linkage strategies such as iterative assembly, motif searches, k-mer frequency profiling, coverage profile binning, and other strategies used to recover genomes of potential viral pathogens in a timely and cost-effective manner.",2015 Oct 1,"['Smits, Saskia L.', 'Bodewes, Rogier', 'Ruiz-González, Aritz', 'Baumgärtner, Wolfgang', 'Koopmans, Marion P.', 'Osterhaus, Albert D. M. E.', 'Schürch, Anita C.']",Front Microbiol,,,True
0910e151cd1fb8d455e54cd4e97f867627f934c8,PMC,Disparities in Spatial Prevalence of Feline Retroviruses due to Data Aggregation: A Case of the Modifiable Areal Unit Problem,http://dx.doi.org/10.1155/2014/424138,PMC4590838,26464932,CC BY,"The knowledge of the spatial distribution feline immunodeficiency virus and feline leukemia virus infections, which are untreatable, can inform on their risk factors and high-risk areas to enhance control. However, when spatial analysis involves aggregated spatial data, results may be influenced by the spatial scale of aggregation, an effect known as the modifiable areal unit problem (MAUP). In this study, area level risk factors for both infections in 28,914 cats tested with ELISA were investigated by multivariable spatial Poisson regression models along with MAUP effect on spatial clustering and cluster detection (for postal codes, counties, and states) by Moran's I test and spatial scan test, respectively. The study results indicate that the significance and magnitude of the association of risk factors with both infections varied with aggregation scale. Further more, Moran's I test only identified spatial clustering at postal code and county levels of aggregation. Similarly, the spatial scan test indicated that the number, size, and location of clusters varied over aggregation scales. In conclusion, the association between infection and area was influenced by the choice of spatial scale and indicates the importance of study design and data analysis with respect to specific research questions.",2014 Feb 19,"['Chhetri, Bimal K.', 'Berke, Olaf', 'Pearl, David L.', 'Bienzle, Dorothee']",J Vet Med,,,True
c3868e20a756883f97b18c851e9e6df7ad0cb11e,PMC,"Adenovirus infection in children with acute lower respiratory tract infections in Beijing, China, 2007 to 2012",http://dx.doi.org/10.1186/s12879-015-1126-2,PMC4591558,26429778,CC BY,"BACKGROUND: Human adenoviruses (HAdV) play a significant role in pediatric respiratory tract infections. To date, over 60 types of HAdV have been identified. Here, HAdV types are characterized in children in the Beijing area with acute lower respiratory tract infections (ALRTIs) and the clinical features and laboratory findings of hospitalized HAdV-infected cases are described. METHODS: Respiratory specimens were collected from pediatric patients with ALRTIs in the emergency department or from those admitted to Beijing Children’s Hospital between March 2007 and December 2012. Infections with common respiratory viruses were determined by PCR or RT-PCR. HAdV positive samples were further typed by PCR and sequencing. RESULTS: Among 3356 patients with ALRTIs, 194 (5.8 %) were found to have HAdV infection. HAdV infection was primarily confined to children (88.35 %) less than 5 years of age. A total of 11 different types of HAdV were detected throughout the study period, with HAdV-B7 (49.0 %) and HAdV-B3 (26.3 %) as the most prevalent types, followed by HAdV-C2 (7.7 %) and HAdVC1 (4.6 %). Newly emerging and re-emergent types or variants, HAdV-B55 (n = 5), HAdV-C57 (n = 3), and HAdV-B14p1 (n = 1), were identified. Results also included the reported first case of co-infection with HAdV-C2 and HAdV-C57. Clinical entities of patients with single HAdV infection (n = 49) were similar to those with mixed HAdV/respiratory syncytial virus (RSV) infections (n = 41). Patients with HAdV-B7 infection had longer duration of fever and higher serum levels of muscle enzymes than HAdV-B3-infected patients. CONCLUSIONS: During the study period, HAdV-B7 and HAdV-B3 were the predominant types identified in pediatric ALRTIs. HAdV-B7 infection tends to have more severe clinical consequences. The presence of newly emerging types or variants and co-infection with different types of HAdV highlights the need for constant and close surveillance of HAdV infection.",2015 Oct 1,"['Liu, Chunyan', 'Xiao, Yan', 'Zhang, Jing', 'Ren, Lili', 'Li, Jianguo', 'Xie, Zhengde', 'Xu, Baoping', 'Yang, Yan', 'Qian, Suyun', 'Wang, Jianwei', 'Shen, Kunling']",BMC Infect Dis,,,True
b973a418c19776904cffc71357c7119485bf2b3a,PMC,The Large Scale Machine Learning in an Artificial Society: Prediction of the Ebola Outbreak in Beijing,http://dx.doi.org/10.1155/2015/531650,PMC4592709,26457078,CC BY,"Ebola virus disease (EVD) distinguishes its feature as high infectivity and mortality. Thus, it is urgent for governments to draw up emergency plans against Ebola. However, it is hard to predict the possible epidemic situations in practice. Luckily, in recent years, computational experiments based on artificial society appeared, providing a new approach to study the propagation of EVD and analyze the corresponding interventions. Therefore, the rationality of artificial society is the key to the accuracy and reliability of experiment results. Individuals' behaviors along with travel mode directly affect the propagation among individuals. Firstly, artificial Beijing is reconstructed based on geodemographics and machine learning is involved to optimize individuals' behaviors. Meanwhile, Ebola course model and propagation model are built, according to the parameters in West Africa. Subsequently, propagation mechanism of EVD is analyzed, epidemic scenario is predicted, and corresponding interventions are presented. Finally, by simulating the emergency responses of Chinese government, the conclusion is finally drawn that Ebola is impossible to outbreak in large scale in the city of Beijing.",2015 Sep 20,"['Zhang, Peng', 'Chen, Bin', 'Ma, Liang', 'Li, Zhen', 'Song, Zhichao', 'Duan, Wei', 'Qiu, Xiaogang']",Comput Intell Neurosci,,,True
4277d45726b61850deb6a0a4b2cabe450127ec69,PMC,Aetiological role of common respiratory viruses in acute lower respiratory infections in children under five years: A systematic review and meta–analysis,http://dx.doi.org/10.7189/jogh.05.010408,PMC4593292,26445672,CC BY,"BACKGROUND: Acute lower respiratory infection (ALRI) remains a major cause of childhood hospitalization and mortality in young children and the causal attribution of respiratory viruses in the aetiology of ALRI is unclear. We aimed to quantify the absolute effects of these viral exposures. METHODS: We conducted a systematic literature review (across 7 databases) of case–control studies published from 1990 to 2014 which investigated the viral profile of 18592 children under 5 years with and without ALRI. We then computed a pooled odds ratio and virus–specific attributable fraction among the exposed of 8 common viruses – respiratory syncytial virus (RSV), influenza (IFV), parainfluenza (PIV), human metapneumovirus (MPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV). FINDINGS: From the 23 studies included, there was strong evidence for causal attribution of RSV (OR 9.79; AFE 90%), IFV (OR 5.10; AFE 80%), PIV (OR 3.37; AFE 70%) and MPV (OR 3.76; AFE 73%), and less strong evidence for RV (OR 1.43; AFE 30%) in young children presenting with ALRI compared to those without respiratory symptoms (asymptomatic) or healthy children. However, there was no significant difference in the detection of AdV, BoV, or CoV in cases and controls. CONCLUSIONS: This review supports RSV, IFV, PIV, MPV and RV as important causes of ALRI in young children, and provides quantitative estimates of the absolute proportion of virus–associated ALRI cases to which a viral cause can be attributed.",,"['Shi, Ting', 'McLean, Kenneth', 'Campbell, Harry', 'Nair, Harish']",J Glob Health.; 5(1):010408,,,True
d49895892511c456d98567b608222314bece919d,PMC,Aetiological role of common respiratory viruses in acute lower respiratory infections in children under five years: A systematic review and meta–analysis,http://dx.doi.org/10.7189/jogh.05.010408,PMC4593292,26445672,CC BY,"BACKGROUND: Acute lower respiratory infection (ALRI) remains a major cause of childhood hospitalization and mortality in young children and the causal attribution of respiratory viruses in the aetiology of ALRI is unclear. We aimed to quantify the absolute effects of these viral exposures. METHODS: We conducted a systematic literature review (across 7 databases) of case–control studies published from 1990 to 2014 which investigated the viral profile of 18592 children under 5 years with and without ALRI. We then computed a pooled odds ratio and virus–specific attributable fraction among the exposed of 8 common viruses – respiratory syncytial virus (RSV), influenza (IFV), parainfluenza (PIV), human metapneumovirus (MPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV). FINDINGS: From the 23 studies included, there was strong evidence for causal attribution of RSV (OR 9.79; AFE 90%), IFV (OR 5.10; AFE 80%), PIV (OR 3.37; AFE 70%) and MPV (OR 3.76; AFE 73%), and less strong evidence for RV (OR 1.43; AFE 30%) in young children presenting with ALRI compared to those without respiratory symptoms (asymptomatic) or healthy children. However, there was no significant difference in the detection of AdV, BoV, or CoV in cases and controls. CONCLUSIONS: This review supports RSV, IFV, PIV, MPV and RV as important causes of ALRI in young children, and provides quantitative estimates of the absolute proportion of virus–associated ALRI cases to which a viral cause can be attributed.",,"['Shi, Ting', 'McLean, Kenneth', 'Campbell, Harry', 'Nair, Harish']",J Glob Health.; 5(1):010408,,,False
2076515c446601717239a974bc7bfc84f455e62c,PMC,Siaα2-3Galβ1- Receptor Genetic Variants Are Associated with Influenza A(H1N1)pdm09 Severity,http://dx.doi.org/10.1371/journal.pone.0139681,PMC4593567,26436774,CC BY,"Different host genetic variants may be related to the virulence and transmissibility of pandemic Influenza A(H1N1)pdm09, influencing events such as binding of the virus to the entry receptor on the cell of infected individuals and the host immune response. In the present study, two genetic variants of the ST3GAL1 gene, which encodes the Siaα2-3Galβ1- receptor to which influenza A(H1N1)pdm09 virus binds for entry into the host cell, were investigated in an admixed Brazilian population. First, the six exons encoding the ST3GAL1 gene were sequenced in 68 patients infected with strain A(H1N1)pdm09. In a second phase of the study, the rs113350588 and rs1048479 polymorphisms identified in this sample were genotyped in a sample of 356 subjects from the northern and northeastern regions of Brazil with a diagnosis of pandemic influenza. Functional analysis of the polymorphisms was performed in silico and the influence of these variants on the severity of infection was evaluated. The results suggest that rs113350588 and rs1048479 may alter the function of ST3GAL1 either directly through splicing regulation alteration and/or indirectly through LD with SNP with regulatory function. In the study the rs113350588 and rs1048479 polymorphisms were in linkage disequilibrium in the population studied (D’ = 0.65). The GC haplotype was associated with an increased risk of death in subjects with influenza (OR = 4.632, 95% CI = 2.10;1.21). The AT haplotype was associated with an increased risk of severe disease and death (OR = 1.993, 95% CI = 1.09;3.61 and OR 4.476, 95% CI = 2.37;8.44, respectively). This study demonstrated for the first time the association of ST3GAL1 gene haplotypes on the risk of more severe disease and death in patients infected with Influenza A(H1N1)pdm09 virus.",2015 Oct 5,"['Maestri, Alvino', 'Sortica, Vinicius Albuquerque', 'Tovo-Rodrigues, Luciana', 'Santos, Mirleide Cordeiro', 'Barbagelata, Luana', 'Moraes, Milene Raiol', 'Alencar de Mello, Wyller', 'Gusmão, Leonor', 'Sousa, Rita Catarina Medeiros', 'Emanuel Batista dos Santos, Sidney']",PLoS One,,,True
70bae0f6fbce9a54e7574b4309c5a3ebd1be7133,PMC,Kinetic characterization of trans-proteolytic activity of Chikungunya virus capsid protease and development of a FRET-based HTS assay,http://dx.doi.org/10.1038/srep14753,PMC4593962,26439734,CC BY,"Chikungunya virus (CHIKV) capsid protein (CVCP) is a serine protease that possesses cis-proteolytic activity essential for the structural polyprotein processing and plays a key role in the virus life cycle. CHIKV being an emerging arthropod-borne pathogenic virus, is a public health concern worldwide. No vaccines or specific antiviral treatment is currently available for chikungunya disease. Thus, it is important to develop inhibitors against CHIKV enzymes to block key steps in viral reproduction. In view of this, CVCP was produced recombinantly and purified to homogeneity. A fluorescence resonance energy transfer (FRET)-based proteolytic assay was developed for high throughput screening (HTS). A FRET peptide substrate (DABCYL-GAEEWSLAIE-EDANS) derived from the cleavage site present in the structural polyprotein of CVCP was used. The assay with a Z’ factor of 0.64 and coefficient of variation (CV) is 8.68% can be adapted to high throughput format for automated screening of chemical libraries to identify CVCP specific protease inhibitors. Kinetic parameters K(m) and k(cat)/K(m) estimated using FRET assay were 1.26 ± 0.34 μM and 1.11 × 10(3) M(−1) sec(−1) respectively. The availability of active recombinant CVCP and cost effective fluorogenic peptide based in vitro FRET assay may serve as the basis for therapeutics development against CHIKV.",2015 Oct 6,"['Aggarwal, Megha', 'Sharma, Rajesh', 'Kumar, Pravindra', 'Parida, Manmohan', 'Tomar, Shailly']",Sci Rep,,,True
6f06d1fd7c4ae1397b0a8f5192e9f0c7dc5e62df,PMC,Effect of Porcine Epidemic Diarrhea Virus Infectious Doses on Infection Outcomes in Naïve Conventional Neonatal and Weaned Pigs,http://dx.doi.org/10.1371/journal.pone.0139266,PMC4594914,26441071,CC BY,"Porcine epidemic diarrhea virus (PEDV) was identified in the United States (U.S.) swine population for the first time in April 2013 and rapidly spread nationwide. However, no information has been published regarding the minimum infectious dose (MID) of PEDV in different pig models. The main objective of this study was to determine the oral minimum infectious dose of PEDV in naïve conventional neonatal piglets and weaned pigs. A U.S. virulent PEDV prototype isolate (USA/IN19338/2013) with known infectious titer was serially ten-fold diluted in virus-negative cell culture medium. Dilutions with theoretical infectious titers from 560 to 0.0056 TCID(50)/ml together with a medium control were orogastrically inoculated (10ml/pig) into 7 groups of 5-day-old neonatal pigs (n = 4 per group) and 7 groups of 21-day-old weaned pigs (n = 6 per group). In 5-day-old pigs, 10ml of inoculum having titers 560–0.056 TCID(50)/ml, corresponding to polymerase chain reaction (PCR) cycle threshold (Ct) values 24.2–37.6, resulted in 100% infection in each group; 10ml of inoculum with titer 0.0056 TCID(50)/ml (Ct>45) caused infection in 25% of the inoculated pigs. In 21-day-old pigs, 10ml of inoculum with titers 560–5.6 TCID(50)/ml (Ct 24.2–31.4) resulted in 100% infection in each group while 10ml of inoculum with titers 0.56–0.0056 TCID(50)/ml (Ct values 35.3 –>45) did not establish infection in any pigs under study conditions as determined by clinical signs, PCR, histopathology, immunohistochemistry, and antibody response. These data reveal that PEDV infectious dose is age-dependent with a significantly lower MID for neonatal pigs compared to weaned pigs. This information should be taken into consideration when interpreting clinical relevance of PEDV PCR results and when designing a PEDV bioassay model. The observation of such a low MID in neonates also emphasizes the importance of strict biosecurity and thorough cleaning/disinfection on sow farms.",2015 Oct 6,"['Thomas, Joseph T.', 'Chen, Qi', 'Gauger, Phillip C.', 'Giménez-Lirola, Luis G.', 'Sinha, Avanti', 'Harmon, Karen M.', 'Madson, Darin M.', 'Burrough, Eric R.', 'Magstadt, Drew R.', 'Salzbrenner, Holly M.', 'Welch, Michael W.', 'Yoon, Kyoung-Jin', 'Zimmerman, Jeffrey J.', 'Zhang, Jianqiang']",PLoS One,,,True
6ac46cebdca71f2e25d8a884c5d3ce11fcaf16e7,PMC,Efficacy and safety of iota-carrageenan nasal spray versus placebo in early treatment of the common cold in adults: the ICICC trial,http://dx.doi.org/10.1186/s12931-015-0281-8,PMC4595062,26438038,CC BY,"ABSTRACT: Iota-carrageenan (I-C) is active against respiratory viruses in vitro and was effective as nasal spray in three previous clinical trials. The current trial served to further investigate I-C in patients with early common cold symptoms. METHODS: This randomized, placebo-controlled, double-blind phase IV trial was conducted in 200 adult patients with self-diagnosed colds of <48 h’ duration that were confirmed by baseline cold symptom scores. Patients were to self-administer 0.12 % I-C or placebo spray (NaCl 0.5 %) four times daily for four to ten days and record symptom information for ten days. Common respiratory viruses were quantified by RT-PCR during pretreatment and on Day 3 or 4. The primary endpoint was the mean total symptom score (TSS) of eight cold symptoms on Days 2–4 (TSS(2–4)). RESULTS: Patients in both treatment groups had similar baseline TSSs (mean TSS: 6.75 for I-C and 6.79 for placebo). Viruses were detected in baseline samples from 53 of 98 I-C patients (54.1 %) and 54 of 97 placebo patients (55.7 %). Mean ± SE for TSS(2–4) was 5.78 ± 0.25 for I-C patients and 6.39 ± 0.25 for placebo (p = 0.0895). Exploratory analyses after unblinding (TSS(2–4) excluding a patient with aberrantly high symptom scores [TSS(2–4, ex 1pt)]; mean of TSS over Days 1–4 [TSS(1–4)]; change in TSS(1–4) relative to baseline [TSS(1–4, rel)]) demonstrated treatment differences in favor of I-C (p = 0.0364, p = 0.0495 and p = 0.0421, respectively). For patients with quantifiable rhinovirus/enterovirus at baseline, there was a trend towards greater reduction of virus load at Day 3 or 4 (p = 0.0958; I-C: 90.2 % reduction in viral load; placebo: 72.0 %). Treatments were well tolerated with no differences in adverse event rates. CONCLUSIONS: The primary endpoint did not demonstrate a statistically significant difference between I-C and placebo but showed a trend towards I-C benefit. Exploratory analyses indicated significant reduction of cold symptoms in the I-C group relative to placebo during the first four days when symptoms were most severe, and also substantiated I-C’s activity against rhinovirus/enterovirus. TRIAL REGISTRATION: NCT01944631 (clinicaltrials.gov)",2015 Oct 5,"['Eccles, R.', 'Winther, B.', 'Johnston, S.L.', 'Robinson, P.', 'Trampisch, M.', 'Koelsch, S.']",Respir Res,,,True
e20c3efee1c9653c22821eb34138d6138daefe40,PMC,8(th) International conference on management and rehabilitation of chronic respiratory failure: the long summaries – Part 3,http://dx.doi.org/10.1186/s40248-015-0028-x,PMC4595187,,CC BY,"This paper summarizes the Part 3 of the proceedings of the 8(th) International Conference on Management and Rehabilitation of Chronic Respiratory Failure, held in Pescara, Italy, on 7 and 8 May, 2015. It summarizes the contributions from numerous experts in the field of chronic respiratory disease and chronic respiratory failure. The outline follows the temporal sequence of presentations. This paper (Part 3) presents a section regarding Moving Across the Spectrum of Care for Long-Term Ventilation (Moving Across the Spectrum of Care for Long-Term Ventilation, New Indications for Non-Invasive Ventilation, Elective Ventilation in Respiratory Failure - Can you Prevent ICU Care in Patients with COPD?, Weaning in Long-Term Acute Care Hospitals in the United States, The Difficult-to-Wean Patient: Comprehensive management, Telemonitoring in Ventilator-Dependent Patients, Ethics and Palliative Care in Critically-Ill Respiratory Patients, and Ethics and Palliative Care in Ventilator-Dependent Patients).",2015 Oct 6,"['Ambrosino, Nicolino', 'Casaburi, Richard', 'Chetta, Alfredo', 'Clini, Enrico', 'Donner, Claudio F.', 'Dreher, Michael', 'Goldstein, Roger', 'Jubran, Amal', 'Nici, Linda', 'Owen, Caroline A.', 'Rochester, Carolyn', 'Tobin, Martin J.', 'Vagheggini, Guido', 'Vitacca, Michele', 'ZuWallack, Richard']",Multidiscip Respir Med,,,True
198399348c2c6a7dafb438b3aaba23b43733b105,PMC,Spillover and pandemic properties of zoonotic viruses with high host plasticity,http://dx.doi.org/10.1038/srep14830,PMC4595845,26445169,CC BY,"Most human infectious diseases, especially recently emerging pathogens, originate from animals, and ongoing disease transmission from animals to people presents a significant global health burden. Recognition of the epidemiologic circumstances involved in zoonotic spillover, amplification, and spread of diseases is essential for prioritizing surveillance and predicting future disease emergence risk. We examine the animal hosts and transmission mechanisms involved in spillover of zoonotic viruses to date, and discover that viruses with high host plasticity (i.e. taxonomically and ecologically diverse host range) were more likely to amplify viral spillover by secondary human-to-human transmission and have broader geographic spread. Viruses transmitted to humans during practices that facilitate mixing of diverse animal species had significantly higher host plasticity. Our findings suggest that animal-to-human spillover of new viruses that are capable of infecting diverse host species signal emerging disease events with higher pandemic potential in that these viruses are more likely to amplify by human-to-human transmission with spread on a global scale.",2015 Oct 7,"['Kreuder Johnson, Christine', 'Hitchens, Peta L.', 'Smiley Evans, Tierra', 'Goldstein, Tracey', 'Thomas, Kate', 'Clements, Andrew', 'Joly, Damien O.', 'Wolfe, Nathan D.', 'Daszak, Peter', 'Karesh, William B.', 'Mazet, Jonna K.']",Sci Rep,,,True
d4c687275097c11a1900e5f627c0c28c998e3d65,PMC,Medicinal herb extracts ameliorate impaired growth performance and intestinal lesion of newborn piglets challenged with the virulent porcine epidemic diarrhea virus,http://dx.doi.org/10.1186/s40781-015-0065-1,PMC4597758,26451253,CC BY,"The objective of this study was to evaluate effects of a combined use of extracts of medicinal herbs Taraxaumi mongolicum, Viola yedoensis Makino, Rhizoma coptidis, and Radix isatidis (MYCI) on porcine epidemic diarrhea (PED). Twenty-two 3-day-old piglets received an oral challenge with 3 × 10(3.5) TCID(50) of the virulent PED virus (PEDV) in PBS or PBS only and daily oral administration of 60 mg of the MYCI mixture suspended in milk replacer or the vehicle for 7 days in a 2 × 2 factorial arrangement of treatments. Average daily gain (ADG) increased (p < 0.05) in response to the MYCI treatment in the PEDV-challenged piglets (−18 vs. 7 g for the vehicle- vs. MYCI-administered group), but not in unchallenged animals (27 vs. 28 g). Diarrhea score and fecal PEDV shedding, however, were not influenced by the MYCI treatment. The PEDV challenge caused severe intestinal villus atrophy and crypt hyperplasia, both of which were alleviated by administration of the MYCI mixture as indicated by an increase in the villus height and a decrease in the crypt depth due to the treatment. Overall, medicinal herb extracts used in this study ameliorated impaired growth performance and intestinal lesion of newborn piglets challenged with the virulent PEDV. Therefore, our results suggest that the MYCI mixture could be used as a prophylactic or therapeutic agent against PED.",2015 Oct 8,"['Kim, Hyeun Bum', 'Lee, Chul Young', 'Kim, Sung Jae', 'Han, Jeong Hee', 'Choi, Keum Hwa']",J Anim Sci Technol,,,True
c74616a5ce5f794dde0644f4cb72bf8a196028a3,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,True
ef29dd8567a7f03ed74ad852bc58826ef98c2694,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
b409b662d80651188e2002a79594263364b73828,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
eb51e093b690e76a91250fd21773bfc034eb41e5,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
1a9668b9c7aeac67694959bcb34c570ab08eebf7,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
a4a438543c6177f81f10993e2b2d3d211642297e,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
0c2ffc7e9950254f236cf4d27f80ea1fadef516f,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
659f4b4eb3c2f8c437a86957f76d166708610d6a,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
c11a9e64e19e76eb7aab68a755341d9d42073d8d,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
13d22e11924648d3aae4f0acc34127c2f9194ef4,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
17eaf34d4dba0463e7957994ff5ab3d7ba2041d4,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
3bfdf7dff1f50821c7fd782b0c6c0b4d56bf1815,PMC,Promoting public health legal preparedness for emergencies: review of current trends and their relevance in light of the Ebola crisis,http://dx.doi.org/10.3402/gha.v8.28871,PMC4598337,26449204,CC BY,"BACKGROUND: Public health legal preparedness (PHLP) for emergencies is a core component of the health system response. However, the implementation of health legal preparedness differs between low- and middle-income countries (LMIC) and developed countries. OBJECTIVE: This paper examines recent trends regarding public health legal preparedness for emergencies and discusses its role in the recent Ebola outbreak. DESIGN: A rigorous literature review was conducted using eight electronic databases as well as Google Scholar. The results encompassed peer-reviewed English articles, reports, theses, and position papers dating from 2011 to 2014. Earlier articles concerning regulatory actions were also examined. RESULTS: The importance of PHLP has grown during the past decade and focuses mainly on infection–disease scenarios. Amid LMICs, it mostly refers to application of international regulations, whereas in developed states, it focuses on independent legislation and creation of conditions optimal to promoting an effective emergency management. Among developed countries, the United States’ utilisation of health legal preparedness is the most advanced, including the creation of a model comprising four elements: law, competencies, information, and coordination. Only limited research has been conducted in this field to date. Nevertheless, in both developed and developing states, studies that focused on regulations and laws activated in health systems during emergencies, identified inconsistency and incoherence. The Ebola outbreak plaguing West Africa since 2014 has global implications, challenges and paralleling results, that were identified in this review. CONCLUSIONS: The review has shown the need to broaden international regulations, to deepen reciprocity between countries, and to consider LMICs health capacities, in order to strengthen the national health security. Adopting elements of the health legal preparedness model is recommended.",2015 Oct 7,"['Cohen, Odeya', 'Feder-Bubis, Paula', 'Bar-Dayan, Yaron', 'Adini, Bruria']",Glob Health Action,,,True
edea2cda674c33bb251b64e5416f5380f13d5489,PMC,Genome Wide Identification of SARS-CoV Susceptibility Loci Using the Collaborative Cross,http://dx.doi.org/10.1371/journal.pgen.1005504,PMC4599853,26452100,CC0,"New systems genetics approaches are needed to rapidly identify host genes and genetic networks that regulate complex disease outcomes. Using genetically diverse animals from incipient lines of the Collaborative Cross mouse panel, we demonstrate a greatly expanded range of phenotypes relative to classical mouse models of SARS-CoV infection including lung pathology, weight loss and viral titer. Genetic mapping revealed several loci contributing to differential disease responses, including an 8.5Mb locus associated with vascular cuffing on chromosome 3 that contained 23 genes and 13 noncoding RNAs. Integrating phenotypic and genetic data narrowed this region to a single gene, Trim55, an E3 ubiquitin ligase with a role in muscle fiber maintenance. Lung pathology and transcriptomic data from mice genetically deficient in Trim55 were used to validate its role in SARS-CoV-induced vascular cuffing and inflammation. These data establish the Collaborative Cross platform as a powerful genetic resource for uncovering genetic contributions of complex traits in microbial disease severity, inflammation and virus replication in models of outbred populations.",2015 Oct 9,"['Gralinski, Lisa E.', 'Ferris, Martin T.', 'Aylor, David L.', 'Whitmore, Alan C.', 'Green, Richard', 'Frieman, Matthew B.', 'Deming, Damon', 'Menachery, Vineet D.', 'Miller, Darla R.', 'Buus, Ryan J.', 'Bell, Timothy A.', 'Churchill, Gary A.', 'Threadgill, David W.', 'Katze, Michael G.', 'McMillan, Leonard', 'Valdar, William', 'Heise, Mark T.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.']",PLoS Genet,,,True
fe2ad749589ac1371ec020700775e8de3c809f41,PMC,The early immune response to infection of chickens with Infectious Bronchitis Virus (IBV) in susceptible and resistant birds,http://dx.doi.org/10.1186/s12917-015-0575-6,PMC4600211,26452558,CC BY,"BACKGROUND: Infectious Bronchitis is a highly contagious respiratory disease which causes tracheal lesions and also affects the reproductive tract and is responsible for large economic losses to the poultry industry every year. This is due to both mortality (either directly provoked by IBV itself or due to subsequent bacterial infection) and lost egg production. The virus is difficult to control by vaccination, so new methods to curb the impact of the disease need to be sought. Here, we seek to identify genes conferring resistance to this coronavirus, which could help in selective breeding programs to rear chickens which do not succumb to the effects of this disease. METHODS: Whole genome gene expression microarrays were used to analyse the gene expression differences, which occur upon infection of birds with Infectious Bronchitis Virus (IBV). Tracheal tissue was examined from control and infected birds at 2, 3 and 4 days post-infection in birds known to be either susceptible or resistant to the virus. The host innate immune response was evaluated over these 3 days and differences between the susceptible and resistant lines examined. RESULTS: Genes and biological pathways involved in the early host response to IBV infection were determined andgene expression differences between susceptible and resistant birds were identified. Potential candidate genes for resistance to IBV are highlighted. CONCLUSIONS: The early host response to IBV is analysed and potential candidate genes for disease resistance are identified. These putative resistance genes can be used as targets for future genetic and functional studies to prove a causative link with resistance to IBV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0575-6) contains supplementary material, which is available to authorized users.",2015 Oct 9,"['Smith, Jacqueline', 'Sadeyen, Jean-Remy', 'Cavanagh, David', 'Kaiser, Pete', 'Burt, David W.']",BMC Vet Res,,,False
4d1f8955a62f01fe7a4d7d19593bdbd6047f4f41,PMC,The early immune response to infection of chickens with Infectious Bronchitis Virus (IBV) in susceptible and resistant birds,http://dx.doi.org/10.1186/s12917-015-0575-6,PMC4600211,26452558,CC BY,"BACKGROUND: Infectious Bronchitis is a highly contagious respiratory disease which causes tracheal lesions and also affects the reproductive tract and is responsible for large economic losses to the poultry industry every year. This is due to both mortality (either directly provoked by IBV itself or due to subsequent bacterial infection) and lost egg production. The virus is difficult to control by vaccination, so new methods to curb the impact of the disease need to be sought. Here, we seek to identify genes conferring resistance to this coronavirus, which could help in selective breeding programs to rear chickens which do not succumb to the effects of this disease. METHODS: Whole genome gene expression microarrays were used to analyse the gene expression differences, which occur upon infection of birds with Infectious Bronchitis Virus (IBV). Tracheal tissue was examined from control and infected birds at 2, 3 and 4 days post-infection in birds known to be either susceptible or resistant to the virus. The host innate immune response was evaluated over these 3 days and differences between the susceptible and resistant lines examined. RESULTS: Genes and biological pathways involved in the early host response to IBV infection were determined andgene expression differences between susceptible and resistant birds were identified. Potential candidate genes for resistance to IBV are highlighted. CONCLUSIONS: The early host response to IBV is analysed and potential candidate genes for disease resistance are identified. These putative resistance genes can be used as targets for future genetic and functional studies to prove a causative link with resistance to IBV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0575-6) contains supplementary material, which is available to authorized users.",2015 Oct 9,"['Smith, Jacqueline', 'Sadeyen, Jean-Remy', 'Cavanagh, David', 'Kaiser, Pete', 'Burt, David W.']",BMC Vet Res,,,True
eb018f450fa6903ccf3c0c151b24a814ee81fd55,PMC,Ring finger protein 166 potentiates RNA virus-induced interferon-β production via enhancing the ubiquitination of TRAF3 and TRAF6,http://dx.doi.org/10.1038/srep14770,PMC4600972,26456228,CC BY,"Host cells orchestrate the production of IFN-β upon detecting invading viral pathogens. Here, we report that Ring finger protein 166 (RNF166) potentiates RNA virus-triggered IFN-β production. Overexpression of RNF166 rather than its homologous proteins RNF114, RNF125, and RNF138, enhanced Sendai virus (SeV)-induced activation of the IFN-β promoter. Knockdown of endogenous RNF166, but not other RNFs, inhibited the IFN-β production induced by SeV and encephalomyocarditis virus. RNF166 interacted with TRAF3 and TRAF6. SeV-induced ubiquitination of TRAF3 and TRAF6 was suppressed when endogenous RNF166 rather than RNF114/138 was knocked down. These findings suggest that RNF166 positively regulates RNA virus-triggered IFN-β production by enhancing the ubiquitination of TRAF3 and TRAF6.",2015 Oct 12,"['Chen, Hai-Wei', 'Yang, Yong-Kang', 'Xu, Hao', 'Yang, Wei-Wei', 'Zhai, Zhong-He', 'Chen, Dan-Ying']",Sci Rep,,,True
cada5ab8069fa39139ce27d9568654e67993adbf,PMC,Positron Emission Tomography With (18)F-Fluorodeoxyglucose in Patients With Sickle Cell Acute Chest Syndrome,http://dx.doi.org/10.1097/MD.0000000000000821,PMC4602525,25950690,CC BY,"The acute chest syndrome (ACS) is the main cause of mortality among adult patients with sickle cell disease (SCD). Its pathophysiology is still unclear. Using positron emission tomography (PET) with (18)F-fluorodeoxyglucose [18F-fluorodeoxyglucose ((18)F-FDG)], we explored the relationship between regional lung density and lung metabolism, as a reflection of lung neutrophilic infiltration during ACS. Patients were prospectively enrolled in a single-center study. Dual modality chest PET/computed tomography (CT) scans were performed, with (18)F-FDG emission scans for quantification of regional (18)F-FDG uptake and CT scans with radiocontrast agent to check for pulmonary artery thrombosis. Regional lung (18)F-FDG uptake was quantified in ACS patients and in SCD patients without ACS (SCD non-ACS controls). Maximal (SUVmax) and mean (SUVmean) standardized uptake values were computed. Seventeen patients with ACS (mean age 28.3 ± 6.4 years) were included. None died nor required invasive mechanical ventilation. The main lung opacity on CT scans was lower lobe consolidation. Lungs of patients with ACS exhibited higher SUVmax than those of SCD non-ACS controls (2.5 [2.1–2.9] vs 0.8 [0.6–1.0]; P < 0.0001). Regional SUVmax and SUVmean was higher in lower than in upper lobes of ACS patients (P < 0.001) with a significant correlation between lung density and SUVmax (R(2) = 0.78). SUVmean was higher in upper lobes of ACS patients than in lungs of SCD non-ACS controls (P < 0.001). Patients with SUVmax >2.5 had longer intensive care unit (ICU) stay than others (7 [6–11] vs 4 [3–6] days; P = 0.016). Lungs of patients with ACS exhibited higher (18)F-FDG uptake than SCD non-ACS controls. Lung apices had normal aeration and lower (18)F-FDG uptake than lung bases, but higher (18)F-FDG uptake than lungs of SCD non-ACS controls. Patients with higher lung (18)F-FDG uptake had longer ICU stay than others.",2015 May 8,"['de Prost, Nicolas', 'Sasanelli, Myriam', 'Deux, Jean-François', 'Habibi, Anoosha', 'Razazi, Keyvan', 'Galactéros, Frédéric', 'Meignan, Michel', 'Maître, Bernard', 'Brun-Buisson, Christian', 'Itti, Emmanuel', 'Dessap, Armand Mekontso']",Medicine (Baltimore),,,True
982210556d79705b5b48d86ca09aadf517bd0edb,PMC,No Direct Association Between Asthma and the Microbiome Based on Currently Available Techniques,http://dx.doi.org/10.1097/MD.0000000000000199,PMC4602810,25501073,CC BY,"Current uses of culture-independent tools in previous studies have shown a significant relationship between microbiota and asthma. Although these studies are relatively new, there is also evidence of the possibility of new therapeutic strategies for the treatment or prevention of asthma. This article retrospectively examines the possible association between microorganisms and asthma. Data on all patients with different types of asthma were collected from hospital charts from the Department of Internal Medicine, Saarland University Medical Center, Germany, within the study period of 2011 to 2012. The tracheal secretions of asthmatics obtained by bronchoalveolar lavage, bronchial aspirates through flexible bronchoscopy, and directly in sputum were examined microbiologically for microorganisms. Thirty-one (10.47%, 95% CI, 6.98–13.96) of a total of 296 patients were found to have asthma microorganisms in their airways. We could not establish a causal relationship between microorganisms and asthma based on the results of our study (P = 0.893). Additionally, acute respiratory infections did not affect the microbiological colonization in asthmatics’ airways (P = 0.472). We were unable to find a direct association between asthma and the microbiome based on existing diagnostic techniques.",2014 Dec 12,"Yayan, Josef",Medicine (Baltimore),,,True
00142f93c18b07350be89e96372d240372437ed9,PMC,Immunity to Pathogens Taught by Specialized Human Dendritic Cell Subsets,http://dx.doi.org/10.3389/fimmu.2015.00527,PMC4603245,26528289,CC BY,"Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) that have a key role in immune responses because they bridge the innate and adaptive arms of the immune system. They mature upon recognition of pathogens and upregulate MHC molecules and costimulatory receptors to activate antigen-specific CD4(+) and CD8(+) T cells. It is now well established that DCs are not a homogeneous population but are composed of different subsets with specialized functions in immune responses to specific pathogens. Upon viral infections, plasmacytoid DCs (pDCs) rapidly produce large amounts of IFN-α, which has potent antiviral functions and activates several other immune cells. However, pDCs are not particularly potent APCs and induce the tolerogenic cytokine IL-10 in CD4(+) T cells. In contrast, myeloid DCs (mDCs) are very potent APCs and possess the unique capacity to prime naive T cells and consequently to initiate a primary adaptive immune response. Different subsets of mDCs with specialized functions have been identified. In mice, CD8α(+) mDCs capture antigenic material from necrotic cells, secrete high levels of IL-12, and prime Th1 and cytotoxic T-cell responses to control intracellular pathogens. Conversely, CD8α(−) mDCs preferentially prime CD4(+) T cells and promote Th2 or Th17 differentiation. BDCA-3(+) mDC2 are the human homologue of CD8α(+) mDCs, since they share the expression of several key molecules, the capacity to cross-present antigens to CD8(+) T-cells and to produce IFN-λ. However, although several features of the DC network are conserved between humans and mice, the expression of several toll-like receptors as well as the production of cytokines that regulate T-cell differentiation are different. Intriguingly, recent data suggest specific roles for human DC subsets in immune responses against individual pathogens. The biology of human DC subsets holds the promise to be exploitable in translational medicine, in particular for the development of vaccines against persistent infections or cancer.",2015 Oct 13,"['Geginat, Jens', 'Nizzoli, Giulia', 'Paroni, Moira', 'Maglie, Stefano', 'Larghi, Paola', 'Pascolo, Steve', 'Abrignani, Sergio']",Front Immunol,,,True
72b1311ad0c502a391201bff5805dcc57ee1c9e1,PMC,The Hepatitis E virus intraviral interactome,http://dx.doi.org/10.1038/srep13872,PMC4604457,26463011,CC BY,"Hepatitis E virus (HEV) is an emerging virus causing epidemic acute hepatitis in developing countries as well as sporadic cases in industrialized countries. The life cycle of HEV is still poorly understood and the lack of efficient cell culture systems and animal models are the principal limitations for a detailed study of the viral replication cycle. Here we exhaustively examine all possible intraviral protein-protein interactions (PPIs) of HEV by systematic Yeast two-hybrid (Y2H) and LuMPIS screens, providing a basis for studying the function of these proteins in the viral replication cycle. Key PPIs correlate with the already published HEV 3D structure. Furthermore, we report 20 novel PPIs including the homodimerization of the RNA dependent RNA polymerase (RdRp), the self-interaction of the papain like protease, and ORF3 interactions with the papain-like protease and putative replicase components: RdRp, methylase and helicase. Furthermore, we determined the dissociation constant (K(d)) of ORF3 interactions with the viral helicase, papain-like protease and methylase, which suggest a regulatory function for ORF3 in orchestrating the formation of the replicase complex. These interactions may represent new targets for antiviral drugs.",2015 Oct 14,"['Osterman, Andreas', 'Stellberger, Thorsten', 'Gebhardt, Anna', 'Kurz, Marisa', 'Friedel, Caroline C.', 'Uetz, Peter', 'Nitschko, Hans', 'Baiker, Armin', 'Vizoso-Pinto, Maria G.']",Sci Rep,,,True
865165018fb3cac831bd7f134dc240d038c25b0c,PMC,The Hepatitis E virus intraviral interactome,http://dx.doi.org/10.1038/srep13872,PMC4604457,26463011,CC BY,"Hepatitis E virus (HEV) is an emerging virus causing epidemic acute hepatitis in developing countries as well as sporadic cases in industrialized countries. The life cycle of HEV is still poorly understood and the lack of efficient cell culture systems and animal models are the principal limitations for a detailed study of the viral replication cycle. Here we exhaustively examine all possible intraviral protein-protein interactions (PPIs) of HEV by systematic Yeast two-hybrid (Y2H) and LuMPIS screens, providing a basis for studying the function of these proteins in the viral replication cycle. Key PPIs correlate with the already published HEV 3D structure. Furthermore, we report 20 novel PPIs including the homodimerization of the RNA dependent RNA polymerase (RdRp), the self-interaction of the papain like protease, and ORF3 interactions with the papain-like protease and putative replicase components: RdRp, methylase and helicase. Furthermore, we determined the dissociation constant (K(d)) of ORF3 interactions with the viral helicase, papain-like protease and methylase, which suggest a regulatory function for ORF3 in orchestrating the formation of the replicase complex. These interactions may represent new targets for antiviral drugs.",2015 Oct 14,"['Osterman, Andreas', 'Stellberger, Thorsten', 'Gebhardt, Anna', 'Kurz, Marisa', 'Friedel, Caroline C.', 'Uetz, Peter', 'Nitschko, Hans', 'Baiker, Armin', 'Vizoso-Pinto, Maria G.']",Sci Rep,,,False
04be45dba1c24d640d5da8298c5f01e3165d84c4,PMC,Association between Use of Oral Anti-Diabetic Drugs and the Risk of Sepsis: A Nested Case-Control Study,http://dx.doi.org/10.1038/srep15260,PMC4604480,26463557,CC BY,"Although oral antidiabetic drugs (OADs) have been associated with immunomodulation in preclinical studies, little is still known about the association between the use of OADs and the risk of sepsis. Using a cohort of patients, extracted from Taiwan’s National Health Insurance Research Database, with type 2 diabetes who were newly diagnosed between 2010 and 2012 and treated with OADs, we conducted a nested case-control study involving 43,015 cases (patients who were first hospitalized for sepsis) and 43,015 matched controls. Compared with non-use, metformin use was associated with a decreased risk of developing sepsis (adjusted odds ratio [OR] 0.80, 95% confidence interval [CI] 0.77–0.83, P < 0.001), but meglitinide (adjusted OR 1.32, 95% CI 1.25–1.40, P < 0.001) use was associated with the increased risk of developing sepsis. The risk for development of sepsis was also lower among current (adjusted OR 0.87, 95% CI 0.78–0.96) and recent (adjusted OR 0.83, 95% CI 0.73–0.94) thiazolidinedione users. Current or recent sulfonylurea use and dipeptidyl peptidase-4 inhibitor use were not significantly associated with the development of sepsis. Our results highlight the need to consider the potential pleiotropic effect of OADs against sepsis in addition to the lowering of blood glucose.",2015 Oct 14,"['Shih, Chia-Jen', 'Wu, Yueh-Lin', 'Chao, Pei-Wen', 'Kuo, Shu-Chen', 'Yang, Chih-Yu', 'Li, Szu-Yuan', 'Ou, Shuo-Ming', 'Chen, Yung-Tai']",Sci Rep,,,True
814ec1dc13c5f446a41d1b3f1becb6495897455a,PMC,"Human polyomavirus type six in respiratory samples from hospitalized children with respiratory tract infections in Beijing, China",http://dx.doi.org/10.1186/s12985-015-0390-5,PMC4604616,26463646,CC BY,"BACKGROUND: HPyV6 is a novel human polyomavirus (HPyV), and neither its natural history nor its prevalence in human disease is well known. Therefore, the epidemiology and phylogenetic status of HPyV6 must be systematically characterized. METHODS: The VP1 gene of HPyV6 was detected with an established TaqMan real-time PCR from nasopharyngeal aspirate specimens collected from hospitalized children with respiratory tract infections. The HPyV6-positive specimens were screened for other common respiratory viruses with real-time PCR assays. RESULTS: The prevalence of HPyV6 was 1.7 % (15/887), and children ≤ 5 years of age accounted for 80 % (12/15) of cases. All 15 HPyV6-positive patients were coinfected with other respiratory viruses, of which influenza virus A (IFVA) (8/15, 53.3 %) and respiratory syncytial virus (7/15, 46.7 %) were most common. All 15 HPyV6-positive patients were diagnosed with lower respiratory tract infections, and their viral loads ranged from 1.38 to 182.42 copies/μl nasopharyngeal aspirate specimen. The most common symptoms were cough (100 %) and fever (86.7 %). The complete 4926-bp genome (BJ376 strain, GenBank accession number KM387421) was amplified and showed 100 % identity to HPyV6 strain 607a. CONCLUSIONS: The prevalence of HPyV6 was 1.7 % in nasopharyngeal aspirate specimens from hospitalized children with respiratory tract infections, as analyzed by real-time PCR. Because the coinfection rate was high and the viral load low, it was not possible to establish a correlation between HPyV6 and respiratory diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0390-5) contains supplementary material, which is available to authorized users.",2015 Oct 13,"['Zheng, Wen-zhi', 'Wei, Tian-li', 'Ma, Fen-lian', 'Yuan, Wu-mei', 'Zhang, Qian', 'Zhang, Ya-xin', 'Cui, Hong', 'Zheng, Li-shu']",Virol J,,,True
d1a76cbc915984f693d508e9024c67d001aa20d6,PMC,Review of economic evaluations of mask and respirator use for protection against respiratory infection transmission,http://dx.doi.org/10.1186/s12879-015-1167-6,PMC4605092,26462473,CC BY,"BACKGROUND: There has been increasing debate surrounding mask and respirator interventions to control respiratory infection transmission in both healthcare and community settings. As decision makers are considering the recommendations they should evaluate how to provide the most efficient protection strategies with minimum costs. The aim of this review is to identify and evaluate the existing economic evaluation literature in this area and to offer advice on how future evaluations on this topic should be conducted. METHODS: We searched the Scopus database for all literature on economic evaluation of mask or respirator use to control respiratory infection transmission. Reference lists from the identified studies were also manually searched. Seven studies met our inclusion criteria from the initial 806 studies identified by the search strategy and our manual search. RESULTS: Five studies considered interventions for seasonal and/or pandemic influenza, with one also considering SARS (Severe Acute Respiratory Syndrome). The other two studies focussed on tuberculosis transmission control interventions. The settings and methodologies of the studies varied greatly. No low-middle income settings were identified. Only one of the reviewed studies cited clinical evidence to inform their mask/respirator intervention effectiveness parameters. Mask and respirator interventions were generally reported by the study authors to be cost saving or cost-effective when compared to no intervention or other control measures, however the evaluations had important limitations. CONCLUSIONS: Given the large cost differential between masks and respirators, there is a need for more comprehensive economic evaluations to compare the relative costs and benefits of these interventions in situations and settings where alternative options are potentially applicable. There are at present insufficient well conducted cost-effectiveness studies to inform decision-makers on the value for money of alternative mask/respirator options.",2015 Oct 13,"['Mukerji, Shohini', 'MacIntyre, C. Raina', 'Newall, Anthony T.']",BMC Infect Dis,,,True
468cd07dc546d39f95529846f303e76f02ae51b3,PMC,Nucleolin stabilizes G-quadruplex structures folded by the LTR promoter and silences HIV-1 viral transcription,http://dx.doi.org/10.1093/nar/gkv897,PMC4605322,26354862,CC BY,"Folding of the LTR promoter into dynamic G-quadruplex conformations has been shown to suppress its transcriptional activity in HIV-1. Here we sought to identify the proteins that control the folding of this region of proviral genome by inducing/stabilizing G-quadruplex structures. The implementation of electrophorethic mobility shift assay and pull-down experiments coupled with mass spectrometric analysis revealed that the cellular protein nucleolin is able to specifically recognize G-quadruplex structures present in the LTR promoter. Nucleolin recognized with high affinity and specificity the majority, but not all the possible G-quadruplexes folded by this sequence. In addition, it displayed greater binding preference towards DNA than RNA G-quadruplexes, thus indicating two levels of selectivity based on the sequence and nature of the target. The interaction translated into stabilization of the LTR G-quadruplexes and increased promoter silencing activity; in contrast, disruption of nucleolin binding in cells by both siRNAs and a nucleolin binding aptamer greatly increased LTR promoter activity. These data indicate that nucleolin possesses a specific and regulated activity toward the HIV-1 LTR promoter, which is mediated by G-quadruplexes. These observations provide new essential insights into viral transcription and a possible low mutagenic target for antiretroviral therapy.",2015 Oct 15,"['Tosoni, Elena', 'Frasson, Ilaria', 'Scalabrin, Matteo', 'Perrone, Rosalba', 'Butovskaya, Elena', 'Nadai, Matteo', 'Palù, Giorgio', 'Fabris, Dan', 'Richter, Sara N.']",Nucleic Acids Res,,,True
912c5e77617283256e75b99546edc81e13af0ef6,PMC,Nucleolin stabilizes G-quadruplex structures folded by the LTR promoter and silences HIV-1 viral transcription,http://dx.doi.org/10.1093/nar/gkv897,PMC4605322,26354862,CC BY,"Folding of the LTR promoter into dynamic G-quadruplex conformations has been shown to suppress its transcriptional activity in HIV-1. Here we sought to identify the proteins that control the folding of this region of proviral genome by inducing/stabilizing G-quadruplex structures. The implementation of electrophorethic mobility shift assay and pull-down experiments coupled with mass spectrometric analysis revealed that the cellular protein nucleolin is able to specifically recognize G-quadruplex structures present in the LTR promoter. Nucleolin recognized with high affinity and specificity the majority, but not all the possible G-quadruplexes folded by this sequence. In addition, it displayed greater binding preference towards DNA than RNA G-quadruplexes, thus indicating two levels of selectivity based on the sequence and nature of the target. The interaction translated into stabilization of the LTR G-quadruplexes and increased promoter silencing activity; in contrast, disruption of nucleolin binding in cells by both siRNAs and a nucleolin binding aptamer greatly increased LTR promoter activity. These data indicate that nucleolin possesses a specific and regulated activity toward the HIV-1 LTR promoter, which is mediated by G-quadruplexes. These observations provide new essential insights into viral transcription and a possible low mutagenic target for antiretroviral therapy.",2015 Oct 15,"['Tosoni, Elena', 'Frasson, Ilaria', 'Scalabrin, Matteo', 'Perrone, Rosalba', 'Butovskaya, Elena', 'Nadai, Matteo', 'Palù, Giorgio', 'Fabris, Dan', 'Richter, Sara N.']",Nucleic Acids Res,,,False
425be277181521bab21a8e64d54657dfdcac6bde,PMC,Detection and characterization of respiratory viruses causing acute respiratory illness and asthma exacerbation in children during three different seasons (2011–2014) in Mexico City,http://dx.doi.org/10.1111/irv.12346,PMC4605408,26289993,CC BY,"BACKGROUND: Viral infections play a significant role in causing acute respiratory infections (ARIs) and exacerbations of chronic diseases. Acute respiratory infections are now the leading cause of mortality in children worldwide, especially in developing countries. Recently, human rhinovirus (HRV) infection has been emerged as an important cause of pneumonia and asthma exacerbation. OBJECTIVES: To determine the role of several viral agents principally, respiratory syncytial virus, and HRV in children with ARIs and their relationship with asthma exacerbation and pneumonia. METHODS: Between October 2011 and March 2014, 432 nasopharyngeal samples of children <15 years of age with ARI hospitalized at a referral hospital for respiratory diseases were tested for the presence of respiratory viruses using a multiplex RT-qPCR. Clinical, epidemiological, and demographic data were collected and associated with symptomatology and viral infections. RESULTS: Viral infections were detected in at least 59·7% of the enrolled patients, with HRV (26·6%) being the most frequently detected. HRV infections were associated with clinical features of asthma and difficulty in breathing such as wheezing (P = 0·0003), supraesternal (P = 0·046), and xiphoid retraction (P = 0·030). HRV subtype C (HRV-C) infections were associated with asthma (P = 0·02). CONCLUSIONS: Human rhinovirus was the virus most commonly detected in pediatric patients with ARI. There is also an association of HRV-C infection with asthma exacerbation, emphasizing the relevance of this virus in severe pediatric respiratory disease.",2015 Nov 13,"['Moreno-Valencia, Yazmin', 'Hernandez-Hernandez, Victor A', 'Romero-Espinoza, Jose A I', 'Coronel-Tellez, Rodrigo H', 'Castillejos-Lopez, Manuel', 'Hernandez, Andres', 'Perez-Padilla, Rogelio', 'Alejandre-Garcia, Alejandro', 'de la Rosa-Zamboni, Daniela', 'Ormsby, Christopher E', 'Vazquez-Perez, Joel A']",Influenza Other Respir Viruses,,,True
bd921a71bee40ea8cb9c3725c6dce6ad0ce5a560,PMC,"Prevalence of human parainfluenza virus in patients with acute respiratory tract infections in Beijing, 2011–2014",http://dx.doi.org/10.1111/irv.12336,PMC4605411,26230490,CC BY,,2015 Nov 13,"['Shi, Weixian', 'Cui, Shujuan', 'Gong, Cheng', 'Zhang, Tiegang', 'Yu, Xiali', 'Li, Aihua', 'Chen, Meng', 'Luo, Ming', 'Huang, Fang']",Influenza Other Respir Viruses,,,True
86c378531ecb4b4d351c844fc4e3e5c9cf49f269,PMC,Elevated transmission of upper respiratory illness among new recruits in military barracks in Thailand,http://dx.doi.org/10.1111/irv.12345,PMC4605412,26271648,CC BY,"BACKGROUND: New recruits within military barracks present conditions favorable for the spread of respiratory pathogens. However, respiratory pathogen transmission in such confined settings in the tropics has not been well studied. METHODS: Recruits in four successive Royal Thai Army basic training classes living in military barracks were monitored for the symptoms of influenza-like illness (ILI) or upper respiratory illness (URI). Classes 1 and 2 were also monitored after basic training. Nasal/throat swabs from acute illnesses were collected and tested by influenza RT-PCR (all four classes). In addition, class 1 had multiplex PCR performed along with the analysis of bed locations within the barracks. RESULTS: Influenza-like illness/upper respiratory illness rates ranged from 4·7 to 6·9 per 100 recruit-weeks in the four classes and generally decreased during the course of basic training (P < 0·05 in three of four classes). Rates during basic training were 1·7 (95% CI: 1·29, 2·29) and 2·5 (95% CI: 1·5, 4·1) times higher than after basic training (classes 1 and 2, respectively). In class 1, coronavirus, parainfluenza virus, and rhinovirus were the most commonly identified respiratory pathogens; only one influenza PCR-positive infection was detected in all four classes. Bed locations of URI/ILI cases in class 1 tended to be in closer proximity to each other. CONCLUSION: Basic training recruits in military barracks in the tropics had high rates of acute respiratory illnesses with illness patterns consistent with external seeding followed by substantial internal transmission. Our findings may contribute to control measures in similar confined settings both within and outside the military.",2015 Nov 13,"['Levy, Jens W', 'Bhoomiboonchoo, Piraya', 'Simasathien, Sriluck', 'Salje, Henrik', 'Huang, Angkana', 'Rangsin, Ram', 'Jarman, Richard G', 'Fernandez, Stefan', 'Klungthong, Chonticha', 'Hussem, Kittinun', 'Gibbons, Robert V', 'Yoon, In-Kyu']",Influenza Other Respir Viruses,,,True
a8f484e668a71d016a40b1fd1de16fbf2e539ebe,PMC,"Viral and atypical bacterial aetiologies of infection in hospitalised patients admitted with clinical suspicion of influenza in Thailand, Vietnam and Indonesia",http://dx.doi.org/10.1111/irv.12326,PMC4605413,25980749,CC BY,"BACKGROUND: Influenza constitutes a leading cause of morbidity and mortality worldwide. There is limited information about the aetiology of infection presenting clinically as influenza in hospitalised adults and children in South-East Asia. Such data are important for future management of respiratory infections. OBJECTIVES: To describe the aetiology of infection presenting clinically as influenza in those hospitalised in South-East Asia. METHODS: Respiratory specimens archived from July 2008 to June 2009 from patients hospitalised with suspected influenza from Indonesia, Thailand and Vietnam were tested for respiratory viruses and atypical bacteria by polymerase chain reaction. RESULTS: A total of 1222 patients’ samples were tested. Of 1222, 776 patients (63·5%) were under the age of 5. Viruses detected included rhinoviruses in 229 of 1222 patients (18·7%), bocaviruses in 200 (16·4%), respiratory syncytial viruses in 144 (11·8%), parainfluenza viruses in 140 (11·5%; PIV1: 32; PIV2: 12; PIV3: 71; PIV4: 25), adenovirus in 102 (8·4%), influenza viruses in 93 (7·6%; influenza A: 77; influenza B: 16) and coronaviruses in 23 (1·8%; OC43: 14; E229: 9). Bacterial pathogens were Mycoplasma pneumoniae (n = 33, 2·7%), Chlamydophila psittaci (n = 2), C. pneumoniae (n = 1), Bordetella pertussis (n = 1) and Legionella pneumophila (n = 2). Overall, in-hospital case fatality rate was 29 of 1222 (2·4%). CONCLUSION: Respiratory viruses were the most commonly detected pathogens in patients hospitalised with a clinical suspicion of influenza. Rhinovirus was the most frequently detected virus, and M. pneumoniae, the most common atypical bacterium. The low number of detected influenza viruses demonstrates a low benefit for empirical oseltamivir therapy, unless during an influenza outbreak.",2015 Nov 13,"['Wertheim, Heiman F L', 'Nadjm, Behzad', 'Thomas, Sherine', 'Malik, Suhud', 'Nguyen, Diep Ngoc Thi', 'Vu, Dung Viet Tien', 'Van Nguyen, Kinh', 'Van Nguyen, Chau Vinh', 'Nguyen, Liem Thanh', 'Tran, Sinh Thi', 'Phung, Thuy Bich Thi', 'Nguyen, Trung Vu', 'Hien, Tran Tinh', 'Nguyen, Uyen Hanh', 'Taylor, Walter', 'Truong, Khanh Huu', 'Ha, Tuan Manh', 'Chokephaibulkit, Kulkanya', 'Farrar, Jeremy', 'Wolbers, Marcel', 'de Jong, Menno D', 'van Doorn, H Rogier', 'Puthavathana, Pilaipan']",Influenza Other Respir Viruses,,,True
0d1ca8ed239b0d50c0dc8a21041a1a1c43045806,PMC,Challenges of the Pandemic Response in Primary Care during Pre-Vaccination Period: A Qualitative Study,http://dx.doi.org/10.1186/s13584-015-0028-5,PMC4606524,26473026,CC BY,"BACKGROUND: During the 2009/A/H1N1 pandemic, the main burden of the patient management fell on primary care physicians (PCPs), and they were the principal implementers of pandemic policies. Broad involvement of PCPs in the pandemic response offered an excellent opportunity to investigate the challenges that they encountered. OBJECTIVE: To examine challenges faced by PCPs as they implemented pandemic policies in Australia, Israel and England before the 2009/A/H1N1 pandemic vaccine became available. METHODS: This is a qualitative descriptive study that employed in-depth semi-structured interviews with 65 PCPs from Australia, Israel and England. The data were analysed thematically to provide a detailed account of the themes. RESULTS: Challenges in three fields of the pandemic response were identified. (i) Consultation of patients was challenged by the high flow of patients, sick and worried-well, the necessity to provide personalised information about the disease during consultations, and unfamiliar antiviral treatment. (ii) Performance of public health responsibilities was complicated in regards to patient segregation and introduction of personal protection measures. (iii) Communication with the health authorities was inefficient, with no established route to provide feedback about the pandemic policies. CONCLUSIONS: The experience of the 2009/A/H1N1 pandemic highlighted the centrality of primary care in the pandemic response. Despite intensive pre-pandemic planning, numerous barriers for implementation of the pandemic policies in primary care were identified. Investigation of three different approaches for involvement of PCPs in the pandemic management showed that none of these approaches worked smoothly.",2015 Oct 15,"['Kunin, Marina', 'Engelhard, Dan', 'Thomas, Shane', 'Ashworth, Mark', 'Piterman, Leon']",Isr J Health Policy Res,,,True
355eb5b5bf565e8e432d8746982b5100764db289,PMC,"Viral Etiology of acute respiratory tract infections in hospitalized children and adults in Shandong Province, China",http://dx.doi.org/10.1186/s12985-015-0388-z,PMC4606902,26467854,CC BY,"BACKGROUND: The dominant viral etiologies responsible for acute respiratory infections (ARIs) are poorly understood, particularly among hospitalized patients. Improved etiological insight is needed to improve clinical management and prevention of ARIs. METHODS: Clinical and demographic information and throat swabs were collected from 607 patients from 2011 to 2013 in Shandong Province, China. Multiplex RT-PCR (SeeplexTM RV detection, Seegene) was performed to detected 12 respiratory viral pathogens. RESULTS: A total of 607 hospitalized patients were enrolled from 2011 to 2013. Viruses were identified in 35.75 % (217/607) of cases, including 78 influenza virus A and B (IVA and IVB), 47 para-influenza viruses (PIVs), 41 respiratory syncytial virus (RSV) and 38 adenovirus (ADV). For the children under 15 year old, the common detected viruses were influenza viruses, RSV, PIVS and ADV, while the principal respiratory viruses were human coronaviruses (HCoV), PIVs, influenza viruses for the old adults. Co-infections with multiple viruses were detected in 15.67 % of patients. Children under 5 years were more likely to have one or more detectable virus associated with their ARI. The peak of ARI caused by the respiratory viruses occurred in winter. CONCLUSION: This study demonstrated respiratory viruses were the major cause of hospitalized ARI patients in Shandong Province, influenza virus was the most common detected, RSV was the highest incidence among the young children (≤5 years). These findings also gave a better understand of virus distribution among different age and seasons, which help to consider potential therapeutic approaches and develop effective prevention strategies for respiratory virus infection.",2015 Oct 14,"['Liu, Ti', 'Li, Zhong', 'Zhang, Shengyang', 'Song, Shaoxia', 'Julong, Wu', 'Lin, Yi', 'Guo, Nongjian', 'Xing, Chunyan', 'Xu, Aiqiang', 'Bi, Zhenqiang', 'Wang, Xianjun']",Virol J,,,True
732dff5e34c82bab1a77fe07eeff62b1a0e44fa7,PMC,Risk Factors for Acute Kidney Injury and In-Hospital Mortality in Patients Receiving Extracorporeal Membrane Oxygenation,http://dx.doi.org/10.1371/journal.pone.0140674,PMC4607159,26469793,CC BY,"BACKGROUND AND OBJECTIVES: Although acute kidney injury (AKI) is the most frequent complication in patients receiving extracorporeal membrane oxygenation (ECMO), few studies have been conducted on the risk factors of AKI. We performed this study to identify the risk factors of AKI associated with in-hospital mortality. METHODS: Data from 322 adult patients receiving ECMO were analyzed. AKI and its stages were defined according to Kidney Disease Improving Global Outcomes (KDIGO) classifications. Variables within 24 h before ECMO insertion were collected and analyzed for the associations with AKI and in-hospital mortality. RESULTS: Stage 3 AKI was associated with in-hospital mortality, with a hazard ratio (HR) (95% CI) of 2.690 (1.472–4.915) compared to non-AKI (p = 0.001). The simplified acute physiology score 2 (SAPS2) and serum sodium level were also associated with in-hospital mortality, with HRs of 1.02 (1.004–1.035) per 1 score increase (p = 0.01) and 1.042 (1.014–1.070) per 1 mmol/L increase (p = 0.003). The initial pump speed of ECMO was significantly related to in-hospital mortality with a HR of 1.333 (1.020–1.742) per 1,000 rpm increase (p = 0.04). The pump speed was also associated with AKI (p = 0.02) and stage 3 AKI (p = 0.03) with ORs (95% CI) of 2.018 (1.129–3.609) and 1.576 (1.058–2.348), respectively. We also found that the red cell distribution width (RDW) above 14.1% was significantly related to stage 3 AKI. CONCLUSION: The initial pump speed of ECMO was a significant risk factor of in-hospital mortality and AKI in patients receiving ECMO. The RDW was a risk factor of stage 3 AKI.",2015 Oct 15,"['Lee, Sung Woo', 'Yu, Mi-yeon', 'Lee, Hajeong', 'Ahn, Shin Young', 'Kim, Sejoong', 'Chin, Ho Jun', 'Na, Ki Young']",PLoS One,,,True
6a86bf34d524aa5e33af0a550e4b3a6928d1e600,PMC,Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan,http://dx.doi.org/10.1186/s13054-015-1083-6,PMC4608327,26472401,CC BY,"INTRODUCTION: Community-acquired pneumonia (CAP) requires prompt treatment, but its diagnosis is complex. Improvement of bacterial CAP diagnosis by biomarkers has been evaluated using chest X-ray infiltrate as the CAP gold standard, producing conflicting results. We analyzed the diagnostic accuracy of biomarkers in suspected CAP adults visiting emergency departments for whom CAP diagnosis was established by an adjudication committee which founded its judgment on a systematic multidetector thoracic CT scan. METHODS: In an ancillary study of a multi-center prospective study evaluating the impact of systematic thoracic CT scan on CAP diagnosis, sensitivity and specificity of C-reactive protein (CRP) and procalcitonin (PCT) were evaluated. Systematic nasopharyngeal multiplex respiratory virus PCR was performed at inclusion. An adjudication committee classified CAP diagnostic probability on a 4-level Likert scale, based on all available data. RESULTS: Two hundred patients with suspected CAP were analyzed. The adjudication committee classified 98 patients (49.0 %) as definite CAP, 8 (4.0 %) as probable, 23 (11.5 %) as possible and excluded in 71 (35.5 %, including 29 patients with pulmonary infiltrates on chest X-ray). Among patients with radiological pulmonary infiltrate, 23 % were finally classified as excluded. Viruses were identified by PCR in 29 % of patients classified as definite. Area under the curve was 0.787 [95 % confidence interval (95 % CI), 0.717 to 0.857] for CRP and 0.655 (95 % CI, 0.570 to 0.739) for PCT to detect definite CAP. CRP threshold at 50 mg/L resulted in a positive predictive value of 0.76 and a negative predictive value of 0.75. No PCT cut-off resulted in satisfactory positive or negative predictive values. CRP and PCT accuracy was not improved by exclusion of the 25 (25.5 %) definite viral CAP cases. CONCLUSIONS: For patients with suspected CAP visiting emergency departments, diagnostic accuracy of CRP and PCT are insufficient to confirm the CAP diagnosis established using a gold standard that includes thoracic CT scan. Diagnostic accuracy of these biomarkers is also insufficient to distinguish bacterial CAP from viral CAP. TRIAL REGISTRATION: ClinicalTrials.gov registry NCT01574066 (February 7, 2012) ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-1083-6) contains supplementary material, which is available to authorized users.",2015 Oct 16,"['Le Bel, Josselin', 'Hausfater, Pierre', 'Chenevier-Gobeaux, Camille', 'Blanc, François-Xavier', 'Benjoar, Mikhael', 'Ficko, Cécile', 'Ray, Patrick', 'Choquet, Christophe', 'Duval, Xavier', 'Claessens, Yann-Erick', None]",Crit Care,,,False
f4ccd54d01adf8df0ef201c6e7ab13d847c2a0f0,PMC,Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan,http://dx.doi.org/10.1186/s13054-015-1083-6,PMC4608327,26472401,CC BY,"INTRODUCTION: Community-acquired pneumonia (CAP) requires prompt treatment, but its diagnosis is complex. Improvement of bacterial CAP diagnosis by biomarkers has been evaluated using chest X-ray infiltrate as the CAP gold standard, producing conflicting results. We analyzed the diagnostic accuracy of biomarkers in suspected CAP adults visiting emergency departments for whom CAP diagnosis was established by an adjudication committee which founded its judgment on a systematic multidetector thoracic CT scan. METHODS: In an ancillary study of a multi-center prospective study evaluating the impact of systematic thoracic CT scan on CAP diagnosis, sensitivity and specificity of C-reactive protein (CRP) and procalcitonin (PCT) were evaluated. Systematic nasopharyngeal multiplex respiratory virus PCR was performed at inclusion. An adjudication committee classified CAP diagnostic probability on a 4-level Likert scale, based on all available data. RESULTS: Two hundred patients with suspected CAP were analyzed. The adjudication committee classified 98 patients (49.0 %) as definite CAP, 8 (4.0 %) as probable, 23 (11.5 %) as possible and excluded in 71 (35.5 %, including 29 patients with pulmonary infiltrates on chest X-ray). Among patients with radiological pulmonary infiltrate, 23 % were finally classified as excluded. Viruses were identified by PCR in 29 % of patients classified as definite. Area under the curve was 0.787 [95 % confidence interval (95 % CI), 0.717 to 0.857] for CRP and 0.655 (95 % CI, 0.570 to 0.739) for PCT to detect definite CAP. CRP threshold at 50 mg/L resulted in a positive predictive value of 0.76 and a negative predictive value of 0.75. No PCT cut-off resulted in satisfactory positive or negative predictive values. CRP and PCT accuracy was not improved by exclusion of the 25 (25.5 %) definite viral CAP cases. CONCLUSIONS: For patients with suspected CAP visiting emergency departments, diagnostic accuracy of CRP and PCT are insufficient to confirm the CAP diagnosis established using a gold standard that includes thoracic CT scan. Diagnostic accuracy of these biomarkers is also insufficient to distinguish bacterial CAP from viral CAP. TRIAL REGISTRATION: ClinicalTrials.gov registry NCT01574066 (February 7, 2012) ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-1083-6) contains supplementary material, which is available to authorized users.",2015 Oct 16,"['Le Bel, Josselin', 'Hausfater, Pierre', 'Chenevier-Gobeaux, Camille', 'Blanc, François-Xavier', 'Benjoar, Mikhael', 'Ficko, Cécile', 'Ray, Patrick', 'Choquet, Christophe', 'Duval, Xavier', 'Claessens, Yann-Erick', None]",Crit Care,,,False
f3d150545162ff3cc253c235011a02a91ee676cb,PMC,Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan,http://dx.doi.org/10.1186/s13054-015-1083-6,PMC4608327,26472401,CC BY,"INTRODUCTION: Community-acquired pneumonia (CAP) requires prompt treatment, but its diagnosis is complex. Improvement of bacterial CAP diagnosis by biomarkers has been evaluated using chest X-ray infiltrate as the CAP gold standard, producing conflicting results. We analyzed the diagnostic accuracy of biomarkers in suspected CAP adults visiting emergency departments for whom CAP diagnosis was established by an adjudication committee which founded its judgment on a systematic multidetector thoracic CT scan. METHODS: In an ancillary study of a multi-center prospective study evaluating the impact of systematic thoracic CT scan on CAP diagnosis, sensitivity and specificity of C-reactive protein (CRP) and procalcitonin (PCT) were evaluated. Systematic nasopharyngeal multiplex respiratory virus PCR was performed at inclusion. An adjudication committee classified CAP diagnostic probability on a 4-level Likert scale, based on all available data. RESULTS: Two hundred patients with suspected CAP were analyzed. The adjudication committee classified 98 patients (49.0 %) as definite CAP, 8 (4.0 %) as probable, 23 (11.5 %) as possible and excluded in 71 (35.5 %, including 29 patients with pulmonary infiltrates on chest X-ray). Among patients with radiological pulmonary infiltrate, 23 % were finally classified as excluded. Viruses were identified by PCR in 29 % of patients classified as definite. Area under the curve was 0.787 [95 % confidence interval (95 % CI), 0.717 to 0.857] for CRP and 0.655 (95 % CI, 0.570 to 0.739) for PCT to detect definite CAP. CRP threshold at 50 mg/L resulted in a positive predictive value of 0.76 and a negative predictive value of 0.75. No PCT cut-off resulted in satisfactory positive or negative predictive values. CRP and PCT accuracy was not improved by exclusion of the 25 (25.5 %) definite viral CAP cases. CONCLUSIONS: For patients with suspected CAP visiting emergency departments, diagnostic accuracy of CRP and PCT are insufficient to confirm the CAP diagnosis established using a gold standard that includes thoracic CT scan. Diagnostic accuracy of these biomarkers is also insufficient to distinguish bacterial CAP from viral CAP. TRIAL REGISTRATION: ClinicalTrials.gov registry NCT01574066 (February 7, 2012) ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-1083-6) contains supplementary material, which is available to authorized users.",2015 Oct 16,"['Le Bel, Josselin', 'Hausfater, Pierre', 'Chenevier-Gobeaux, Camille', 'Blanc, François-Xavier', 'Benjoar, Mikhael', 'Ficko, Cécile', 'Ray, Patrick', 'Choquet, Christophe', 'Duval, Xavier', 'Claessens, Yann-Erick', None]",Crit Care,,,True
906246292449c131afd43009c5863e51ab99efc1,PMC,Why Do We Feel Sick When Infected—Can Altruism Play a Role?,http://dx.doi.org/10.1371/journal.pbio.1002276,PMC4608734,26474156,CC BY,"When we contract an infection, we typically feel sick and behave accordingly. Symptoms of sickness behavior (SB) include anorexia, hypersomnia, depression, and reduced social interactions. SB affects species spanning from arthropods to vertebrates, is triggered nonspecifically by viruses, bacteria, and parasites, and is orchestrated by a complex network of cytokines and neuroendocrine pathways; clearly, it has been naturally selected. Nonetheless, SB seems evolutionarily costly: it promotes starvation and predation and reduces reproductive opportunities. How could SB persist? Former explanations focused on individual fitness, invoking improved resistance to pathogens. Could prevention of disease transmission, propagating in populations through kin selection, also contribute to SB?",2015 Oct 16,"['Shakhar, Keren', 'Shakhar, Guy']",PLoS Biol,,,True
f98d0564028d3963a79b75d9bd46fe5a1a5b8541,PMC,"Serological Evidence of MERS-CoV Antibodies in Dromedary Camels (Camelus dromedaries) in Laikipia County, Kenya",http://dx.doi.org/10.1371/journal.pone.0140125,PMC4608777,26473733,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently identified virus causing severe viral respiratory illness in people. Little is known about the reservoir in the Horn of Africa. In Kenya, where no human MERS cases have been reported, our survey of 335 dromedary camels, representing nine herds in Laikipia County, showed a high seroprevalence (46.9%) to MERS-CoV antibodies. Between herd differences were present (14.3%– 82.9%), but was not related to management type or herd isolation. Further research should focus on identifying similarity between MERS-CoV viral isolates in Kenya and clinical isolates from the Middle East and elsewhere.",2015 Oct 16,"['Deem, Sharon L.', 'Fèvre, Eric M.', 'Kinnaird, Margaret', 'Browne, A. Springer', 'Muloi, Dishon', 'Godeke, Gert-Jan', 'Koopmans, Marion', 'Reusken, Chantal B.']",PLoS One,,,True
41ed8edac17db0256c043cee4b27884395539746,PMC,Global Dynamics of a Virus Dynamical Model with Cell-to-Cell Transmission and Cure Rate,http://dx.doi.org/10.1155/2015/758362,PMC4609528,26504489,CC BY,"The cure effect of a virus model with both cell-to-cell transmission and cell-to-virus transmission is studied. By the method of next generation matrix, the basic reproduction number is obtained. The locally asymptotic stability of the virus-free equilibrium and the endemic equilibrium is considered by investigating the characteristic equation of the model. The globally asymptotic stability of the virus-free equilibrium is proved by constructing suitable Lyapunov function, and the sufficient condition for the globally asymptotic stability of the endemic equilibrium is obtained by constructing suitable Lyapunov function and using LaSalle invariance principal.",2015 Oct 1,"['Zhang, Tongqian', 'Meng, Xinzhu', 'Zhang, Tonghua']",Comput Math Methods Med,,,True
d44571bd848bc813e4cdd2fe8c36b922433ec4da,PMC,Infection as an Environmental Trigger of Multiple Sclerosis Disease Exacerbation,http://dx.doi.org/10.3389/fimmu.2015.00520,PMC4609887,26539193,CC BY,"Over the past several decades, significant advances have been made in identifying factors that contribute to the pathogenesis of multiple sclerosis (MS) and have culminated in the approval of some effective therapeutic strategies for disease intervention. However, the mechanisms by which environmental factors, such as infection, contribute to the pathogenesis and/or symptom exacerbation remain to be fully elucidated. Relapse frequency in MS patients contributes to neurological impairment and, in the initial phases of disease, serves as a predictor of poor disease prognosis. The purpose of this review is to examine the evidence that supports a role for peripheral infection in modulating the natural history of this disease. Evidence supporting a role for infection in promoting exacerbation in animal models of MS is also reviewed. Finally, a few mechanisms by which infection may exacerbate symptoms of MS and other neurological diseases are discussed. Those who comprise the majority of MS patients acquire approximately two upper-respiratory infections per year; furthermore, this type of infection doubles the risk for MS relapse, underscoring the contribution of this relationship as being potentially important and particularly detrimental.",2015 Oct 19,"Steelman, Andrew J.",Front Immunol,,,True
aa833047a4b1e39dcdacffc2d5e219ffa4ddb06b,PMC,"Big city, small world: density, contact rates, and transmission of dengue across Pakistan",http://dx.doi.org/10.1098/rsif.2015.0468,PMC4614486,26468065,CC BY,"Macroscopic descriptions of populations commonly assume that encounters between individuals are well mixed; i.e. each individual has an equal chance of coming into contact with any other individual. Relaxing this assumption can be challenging though, due to the difficulty of acquiring detailed knowledge about the non-random nature of encounters. Here, we fitted a mathematical model of dengue virus transmission to spatial time-series data from Pakistan and compared maximum-likelihood estimates of ‘mixing parameters’ when disaggregating data across an urban–rural gradient. We show that dynamics across this gradient are subject not only to differing transmission intensities but also to differing strengths of nonlinearity due to differences in mixing. Accounting for differences in mobility by incorporating two fine-scale, density-dependent covariate layers eliminates differences in mixing but results in a doubling of the estimated transmission potential of the large urban district of Lahore. We furthermore show that neglecting spatial variation in mixing can lead to substantial underestimates of the level of effort needed to control a pathogen with vaccines or other interventions. We complement this analysis with estimates of the relationships between dengue transmission intensity and other putative environmental drivers thereof.",2015 Oct 6,"['Kraemer, M. U. G.', 'Perkins, T. A.', 'Cummings, D. A. T.', 'Zakar, R.', 'Hay, S. I.', 'Smith, D. L.', 'Reiner, R. C.']",J R Soc Interface,,,True
c125f2b3071406f51b9b9aee860030b2f402ee77,PMC,Alterations in stress granule dynamics driven by TDP-43 and FUS: a link to pathological inclusions in ALS?,http://dx.doi.org/10.3389/fncel.2015.00423,PMC4615823,26557057,CC BY,"Stress granules (SGs) are RNA-containing cytoplasmic foci formed in response to stress exposure. Since their discovery in 1999, over 120 proteins have been described to be localized to these structures (in 154 publications). Most of these components are RNA binding proteins (RBPs) or are involved in RNA metabolism and translation. SGs have been linked to several pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In ALS and FTD, the majority of cases have no known etiology and exposure to external stress is frequently proposed as a contributor to either disease initiation or the rate of disease progression. Of note, both ALS and FTD are characterized by pathological inclusions, where some well-known SG markers localize with the ALS related proteins TDP-43 and FUS. We propose that TDP-43 and FUS serve as an interface between genetic susceptibility and environmental stress exposure in disease pathogenesis. Here, we will discuss the role of TDP-43 and FUS in SG dynamics and how disease-linked mutations affect this process.",2015 Oct 23,"['Aulas, Anaïs', 'Vande Velde, Christine']",Front Cell Neurosci,,,True
409e8fa9c8b69d7982ac0ecc28437a2e8a246d2a,PMC,Strengthening epidemiologic investigation of infectious diseases in Korea: lessons from the Middle East Respiratory Syndrome outbreak,http://dx.doi.org/10.4178/epih/e2015040,PMC4616012,26493654,CC BY,"The recent outbreak of Middle East Respiratory Syndrome (MERS) coronavirus infection in Korea resulted in large socioeconomic losses. This provoked the Korean government and the general public to recognize the importance of having a well-established system against infectious diseases. Although epidemiologic investigation is one of the most important aspects of prevention, it has been pointed out that much needs to be improved in Korea. We review here the current status of the Korean epidemiologic service and suggest possible supplementation measures. We examine the current national preventive infrastructure, including human resources such as Epidemic Intelligence Service officers, its governmental management, and related policies. In addition, we describe the practical application of these resources to the recent MERS outbreak and the progress in preventive measures. The spread of MERS demonstrated that the general readiness for emerging infectious diseases in Korea is considerably low. We believe that it is essential to increase society’s investment in disease prevention. Fostering public health personnel, legislating management policies, and establishing research centers for emerging infectious diseases are potential solutions. Evaluating international preventive systems, developing cooperative measures, and initiating improvements are necessary. We evaluated the Korean epidemiologic investigation system and the public preventive measures against infectious diseases in light of the recent MERS outbreak. We suggest that governmental authorities in Korea enforce preventive policies, foster the development of highly qualified personnel, and increase investment in the public health domain of infectious disease prevention.",2015 Sep 16,"['Lee, Changhwan', 'Ki, Moran']",Epidemiol Health,,,True
2386a5c1d03abfd621c25515dcb087174ff54e0a,PMC,Strengthening epidemiologic investigation of infectious diseases in Korea: lessons from the Middle East Respiratory Syndrome outbreak,http://dx.doi.org/10.4178/epih/e2015040,PMC4616012,26493654,CC BY,"The recent outbreak of Middle East Respiratory Syndrome (MERS) coronavirus infection in Korea resulted in large socioeconomic losses. This provoked the Korean government and the general public to recognize the importance of having a well-established system against infectious diseases. Although epidemiologic investigation is one of the most important aspects of prevention, it has been pointed out that much needs to be improved in Korea. We review here the current status of the Korean epidemiologic service and suggest possible supplementation measures. We examine the current national preventive infrastructure, including human resources such as Epidemic Intelligence Service officers, its governmental management, and related policies. In addition, we describe the practical application of these resources to the recent MERS outbreak and the progress in preventive measures. The spread of MERS demonstrated that the general readiness for emerging infectious diseases in Korea is considerably low. We believe that it is essential to increase society’s investment in disease prevention. Fostering public health personnel, legislating management policies, and establishing research centers for emerging infectious diseases are potential solutions. Evaluating international preventive systems, developing cooperative measures, and initiating improvements are necessary. We evaluated the Korean epidemiologic investigation system and the public preventive measures against infectious diseases in light of the recent MERS outbreak. We suggest that governmental authorities in Korea enforce preventive policies, foster the development of highly qualified personnel, and increase investment in the public health domain of infectious disease prevention.",2015 Sep 16,"['Lee, Changhwan', 'Ki, Moran']",Epidemiol Health,,,False
fb6c8bb97e2115a2551f7a278889f3dd54c538fb,PMC,Islet Xeno/transplantation and the risk of contagion: local responses from Canada and Australia to an emerging global technoscience,http://dx.doi.org/10.1186/s40504-015-0030-2,PMC4617985,26497322,CC BY,"This paper situates the public debate over the use of living animal organs and tissue for human therapies within the history of experimental islet transplantation. Specifically, the paper compares and contrasts the Canadian and Australian responses on xenotransplantation to consider what lessons can be learnt about the regulation of a complex and controversial biotechnology. Sobbrio and Jorqui described public engagement on xenotransplantation in these countries as ‘important forms of experimental democracy.’ While Canada experimented with a novel nation-wide public consultation, Australia sought public input within the context of a national inquiry. In both instances, the outcome was a temporary moratorium on all forms of clinical xenotransplantation comparable to the policies adopted in some European countries. In addition, the Australian xenotransplantation ban coincided with a temporary global ban on experimental islet allotransplantation in 2007. Through historical and comparative research, this paper investigates how public controversies over organ and tissue transplantation can inform our understanding of the mediation of interspeciality and the regulation of a highly contested technoscience. It offers an alternative perspective on the xenotransplantation controversy by exploring the ways in which coinciding moratoriums on islet allograft and xenograft challenge, complicate and confound our assumptions regarding the relationships between human and animal, between routine surgery and clinical experimentation, between biomedical science and social science, and between disease risks and material contagion.",2015 Oct 23,"Cheng, Myra",Life Sci Soc Policy,,,True
e6b8ff26b423ef6507f006d69f9a183fb1147988,PMC,The More the Better? A Comparison of the Information Sources Used by the Public during Two Infectious Disease Outbreaks,http://dx.doi.org/10.1371/journal.pone.0140028,PMC4618063,26485302,CC BY,"Recent infectious disease outbreaks have resulted in renewed recognition of the importance of risk communication planning and execution to public health control strategies. Key to these efforts is public access to information that is understandable, reliable and meets their needs for informed decision-making on protective health behaviours. Learning from the trends in sources used in previous outbreaks will enable improvements in information access in future outbreaks. Two separate random-digit dialled telephone surveys were conducted in Alberta, Canada, to explore information sources used by the public, together with their perceived usefulness and credibility, during the 2003 Severe Acute Respiratory Syndrome (SARS) epidemic (n = 1209) and 2009–2010 H1N1 pandemic (n = 1206). Traditional mass media were the most used information sources in both surveys. Although use of the Internet increased from 25% during SARS to 56% during H1N1, overall use of social media was not as high as anticipated. Friends and relatives were commonly used as an information source, but were not deemed very useful or credible. Conversely, doctors and health professionals were considered credible, but not consulted as frequently. The use of five or more information sources increased by almost 60% between the SARS and H1N1 surveys. There was a shift to older, more educated and more affluent respondents between the surveys, most likely caused by a decrease in the use of landlines amongst younger Canadians. It was concluded that people are increasingly using multiple sources of health risk information, presumably in a complementary manner. Subsequently, although using online media is important, this should be used to augment rather than replace more traditional information channels. Efforts should be made to improve knowledge transfer to health care professionals and doctors and provide them with opportunities to be more accessible as information sources. Finally, the future use of telephone surveys needs to account for the changing demographics of the respondents accessed through such surveys.",2015 Oct 20,"['Jardine, Cynthia G.', 'Boerner, Franziska U.', 'Boyd, Amanda D.', 'Driedger, S. Michelle']",PLoS One,,,True
cd67f336a7356dd88e971d3541829bdc290257f4,PMC,Evaluating Subcriticality during the Ebola Epidemic in West Africa,http://dx.doi.org/10.1371/journal.pone.0140651,PMC4618845,26484544,CC BY,"The 2014–2015 Ebola outbreak is the largest and most widespread to date. In order to estimate ongoing transmission in the affected countries, we estimated the weekly average number of secondary cases caused by one individual infected with Ebola throughout the infectious period for each affected West African country using a stochastic hidden Markov model fitted to case data from the World Health Organization. If the average number of infections caused by one Ebola infection is less than 1.0, the epidemic is subcritical and cannot sustain itself. The epidemics in Liberia and Sierra Leone have approached subcriticality at some point during the epidemic; the epidemic in Guinea is ongoing with no evidence that it is subcritical. Response efforts to control the epidemic should continue in order to eliminate Ebola cases in West Africa.",2015 Oct 20,"['Enanoria, Wayne T. A.', 'Worden, Lee', 'Liu, Fengchen', 'Gao, Daozhou', 'Ackley, Sarah', 'Scott, James', 'Deiner, Michael', 'Mwebaze, Ernest', 'Ip, Wui', 'Lietman, Thomas M.', 'Porco, Travis C.']",PLoS One,,,True
417754f2c930dac6e586d36eb8bfb07355f6e0ff,PMC,Feasibility of a birth cohort study dedicated to assessing acute infections using symptom diaries and parental collection of biomaterials,http://dx.doi.org/10.1186/s12879-015-1189-0,PMC4618955,26493700,CC BY,"BACKGROUND: A birth cohort dedicated to studying infections in early childhood may be assisted by parental recording of symptoms on a daily basis and a collection of biomaterials. We aimed at testing the feasibility of this approach for use in a long-term study focusing on infections in children in Germany. METHODS: Parents of 1- to 3-year-old children (n = 75) were recruited in nursery schools. They were asked to complete a symptom diary on a daily basis and to take monthly and symptom-triggered nasal swabs and stool samples from their child over the study period of three months. Feasibility was measured by means of the return proportions of symptom diaries and bio samples; acceptance was assessed by a questionnaire delivered to participants at the end of the study. RESULTS: The majority of the participants filled in the symptom diary during the three months study for 75 or more days (77.3 %), and provided the monthly nasal swabs (62.7 %) and stool samples (65.3 %). The time needed for the tasks was acceptable for most participants (symptom diary: 92.3 %, nasal swabs: 98.5 %, stool samples: 100.0 %). In 64.3 % of the symptom-triggered nasal swabs, respiratory viruses were found compared to 55.5 % in throat swabs taken by health-care professionals within the “ARE surveillance Lower Saxony”, a special project by the Governmental Institute of Public Health of Lower Saxony to investigate causal pathogens for acute respiratory infections in children. CONCLUSIONS: The parental assessment of symptoms and collection of biomaterials in a birth cohort dedicated to studying infections appears feasible in a middle class German population. The success of the study will depend on the ability to maintain these activities over a long time period. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1189-0) contains supplementary material, which is available to authorized users.",2015 Oct 22,"['Zoch, Beate', 'Karch, André', 'Dreesman, Johannes', 'Monazahian, Masyar', 'Baillot, Armin', 'Mikolajczyk, Rafael T.']",BMC Infect Dis,,,True
62189c3e0d5823002bc5785f7acc61d89fb85666,PMC,Design and optimization of peptide nanoparticles,http://dx.doi.org/10.1186/s12951-015-0119-z,PMC4619341,26498651,CC BY,"BACKGROUND: Various supra-molecular structures form by self-assembly of proteins in a symmetric fashion. Examples of such structures are viruses, some bacterial micro-compartments and eukaryotic vaults. Peptide/protein-based nanoparticles are emerging in synthetic biology for a variety of biomedical applications, mainly as drug targeting and delivery systems or as vaccines. Our self-assembling peptide nanoparticles (SAPNs) are formed by a single peptide chain that consists of two helical coiled-coil segments connected by a short linker region. One helix is forming a pentameric coiled coil while the other is forming a trimeric coiled coil. RESULTS: Here, we were studying in vitro and in silico the effect of the chain length and of point mutations near the linker region between the pentamer and the trimer on the self-assembly of the SAPNs. 60 identical peptide chains co-assemble to form a spherical nanoparticle displaying icosahedral symmetry. We have stepwise reduced the size of the protein chain to a minimal chain length of 36 amino acids. We first used biochemical and biophysical methods on the longer constructs followed by molecular dynamics simulations to study eleven different smaller peptide constructs. We have identified one peptide that shows the most promising mini-nanoparticle model in silico. CONCLUSIONS: An approach of in silico modeling combined with in vitro testing and verification yielded promising peptide designs: at a minimal chain length of only 36 amino acids they were able to self-assemble into proper nanoparticles. This is important since the production cost increases more than linearly with chain length. Also the size of the nanoparticles is significantly smaller than 20 nm, thus reducing the immunogenicity of the particles, which in turn may allow to use the SAPNs as drug delivery systems without the risk of an anaphylactic shock. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12951-015-0119-z) contains supplementary material, which is available to authorized users.",2015 Oct 24,"['Doll, Tais A. P. F.', 'Dey, Raja', 'Burkhard, Peter']",J Nanobiotechnology,,,True
693b013cbc9a762c6116b82a671e2eb24b1731b6,PMC,Antibody Derived Peptides for Detection of Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.pone.0135859,PMC4619498,26489048,CC BY,"BACKGROUND: Current Ebola virus (EBOV) detection methods are costly and impractical for epidemic scenarios. Different immune-based assays have been reported for the detection and quantification of Ebola virus (EBOV) proteins. In particular, several monoclonal antibodies (mAbs) have been described that bind the capsid glycoprotein (GP) of EBOV GP. However, the currently available platforms for the design and production of full-length mAbs are cumbersome and costly. The use of antibody fragments, rather than full-length antibodies, might represent a cost-effective alternative for the development of diagnostic and possibly even therapeutic alternatives for EBOV. METHODS/PRINCIPAL FINDINGS: We report the design and expression of three recombinant anti-GP mAb fragments in Escherichia coli cultures. These fragments contained the heavy and light variable portions of the three well-studied anti-GP full-length mAbs 13C6, 13F6, and KZ52, and are consequently named scFv-13C6, scFv-13F6, and Fab-KZ52, respectively. All three fragments exhibited specific anti-GP binding activity in ELISA experiments comparable to that of full-length anti-GP antibodies (i.e., the same order of magnitude) and they are easily and economically produced in bacterial cultures. CONCLUSION/SIGNIFICANCE: Antibody fragments might represent a useful, effective, and low cost alternative to full-length antibodies in Ebola related capture and diagnostics applications.",2015 Oct 21,"['Rodríguez-Martínez, Luis Mario', 'Marquez-Ipiña, Alan Roberto', 'López-Pacheco, Felipe', 'Pérez-Chavarría, Roberto', 'González-Vázquez, Juan Carlos', 'González-González, Everardo', 'Trujillo-de Santiago, Grissel', 'Ponce-Ponce de León, César Alejandro', 'Zhang, Yu Shrike', 'Dokmeci, Mehmet Remzi', 'Khademhosseini, Ali', 'Alvarez, Mario Moisés']",PLoS One,,,True
1926a717f92225eb7539c0fe190cefe1b067f08e,PMC,Assessment of reference gene stability in Rice stripe virus and Rice black streaked dwarf virus infection rice by quantitative Real-time PCR,http://dx.doi.org/10.1186/s12985-015-0405-2,PMC4619528,26497487,CC BY,"BACKGROUND: Stably expressed reference gene(s) normalization is important for the understanding of gene expression patterns by quantitative Real-time PCR (RT-qPCR), particularly for Rice stripe virus (RSV) and Rice black streaked dwarf virus (RBSDV) that caused seriously damage on rice plants in China and Southeast Asia. METHODS: The expression of fourteen common used reference genes of Oryza sativa L. were evaluated by RT-qPCR in RSV and RBSDV infected rice plants. Suitable normalization reference gene(s) were identified by geNorm and NormFinder algorithms. RESULTS: UBQ 10 + GAPDH and UBC + Actin1 were identified as suitable reference genes for RT-qPCR normalization under RSV and RBSDV infection, respectively. When using multiple reference genes, the expression patterns of OsPRIb and OsWRKY, two virus resistance genes, were approximately similar with that reported previously. Comparatively, by using single reference gene (TIP41-Like), a weaker inducible response was observed. CONCLUSIONS: We proposed that the combination of two reference genes could obtain more accurate and reliable normalization of RT-qPCR results in RSV- and RBSDV-infected plants. This work therefore sheds light on establishing a standardized RT-qPCR procedure in RSV- and RBSDV-infected rice plants, and might serve as an important point for discovering complex regulatory networks and identifying genes relevant to biological processes or implicated in virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0405-2) contains supplementary material, which is available to authorized users.",2015 Oct 24,"['Fang, Peng', 'Lu, Rongfei', 'Sun, Feng', 'Lan, Ying', 'Shen, Wenbiao', 'Du, Linlin', 'Zhou, Yijun', 'Zhou, Tong']",Virol J,,,True
8b33d1cedd5e6f39a2609b233d7070e3ddf52831,PMC,Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III,http://dx.doi.org/10.1371/journal.pntd.0004167,PMC4619746,26495991,CC0,"Formalin-inactivated Japanese encephalitis virus (JEV) vaccines are widely available, but the effects of formalin inactivation on the antigenic structure of JEV and the profile of antibodies elicited after vaccination are not well understood. We used a panel of monoclonal antibodies (MAbs) to map the antigenic structure of live JEV virus, untreated control virus (UCV), formalin-inactivated commercial vaccine (FICV), and formalin-inactivated virus (FIV). The binding activity of T16 MAb against Nakayama-derived FICV and several strains of FIV was significantly lower compared to live virus and UCV. T16 MAb, a weakly neutralizing JEV serocomplex antibody, was found to inhibit JEV infection at the post-attachment step. The T16 epitope was mapped to amino acids 329, 331, and 389 within domain III (EDIII) of the envelope (E) glycoprotein. When we explored the effect of formalin inactivation on the immunogenicity of JEV, we found that Nakayama-derived FICV, FIV, and UCV all exhibited similar immunogenicity in a mouse model, inducing anti-JEV and anti-EDII 101/106/107 epitope-specific antibodies. However, the EDIII 329/331/389 epitope-specific IgG antibody and neutralizing antibody titers were significantly lower for FICV-immunized and FIV-immunized mouse serum than for UCV-immunized. Formalin inactivation seems to alter the antigenic structure of the E protein, which may reduce the potency of commercially available JEV vaccines. Virus inactivation by H(2)O(2), but not by UV or by short-duration and higher temperature formalin treatment, is able to maintain the antigenic structure of the JEV E protein. Thus, an alternative inactivation method, such as H(2)O(2), which is able to maintain the integrity of the E protein may be essential to improving the potency of inactivated JEV vaccines.",2015 Oct 23,"['Fan, Yi-Chin', 'Chiu, Hsien-Chung', 'Chen, Li-Kuang', 'Chang, Gwong-Jen J.', 'Chiou, Shyan-Song']",PLoS Negl Trop Dis,,,True
e1f5129f1f4480a910c93ff7bb33fec50d68feea,PMC,Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III,http://dx.doi.org/10.1371/journal.pntd.0004167,PMC4619746,26495991,CC0,"Formalin-inactivated Japanese encephalitis virus (JEV) vaccines are widely available, but the effects of formalin inactivation on the antigenic structure of JEV and the profile of antibodies elicited after vaccination are not well understood. We used a panel of monoclonal antibodies (MAbs) to map the antigenic structure of live JEV virus, untreated control virus (UCV), formalin-inactivated commercial vaccine (FICV), and formalin-inactivated virus (FIV). The binding activity of T16 MAb against Nakayama-derived FICV and several strains of FIV was significantly lower compared to live virus and UCV. T16 MAb, a weakly neutralizing JEV serocomplex antibody, was found to inhibit JEV infection at the post-attachment step. The T16 epitope was mapped to amino acids 329, 331, and 389 within domain III (EDIII) of the envelope (E) glycoprotein. When we explored the effect of formalin inactivation on the immunogenicity of JEV, we found that Nakayama-derived FICV, FIV, and UCV all exhibited similar immunogenicity in a mouse model, inducing anti-JEV and anti-EDII 101/106/107 epitope-specific antibodies. However, the EDIII 329/331/389 epitope-specific IgG antibody and neutralizing antibody titers were significantly lower for FICV-immunized and FIV-immunized mouse serum than for UCV-immunized. Formalin inactivation seems to alter the antigenic structure of the E protein, which may reduce the potency of commercially available JEV vaccines. Virus inactivation by H(2)O(2), but not by UV or by short-duration and higher temperature formalin treatment, is able to maintain the antigenic structure of the JEV E protein. Thus, an alternative inactivation method, such as H(2)O(2), which is able to maintain the integrity of the E protein may be essential to improving the potency of inactivated JEV vaccines.",2015 Oct 23,"['Fan, Yi-Chin', 'Chiu, Hsien-Chung', 'Chen, Li-Kuang', 'Chang, Gwong-Jen J.', 'Chiou, Shyan-Song']",PLoS Negl Trop Dis,,,False
1f408749f93253eda073910a5b05fcc8e01eead2,PMC,Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III,http://dx.doi.org/10.1371/journal.pntd.0004167,PMC4619746,26495991,CC0,"Formalin-inactivated Japanese encephalitis virus (JEV) vaccines are widely available, but the effects of formalin inactivation on the antigenic structure of JEV and the profile of antibodies elicited after vaccination are not well understood. We used a panel of monoclonal antibodies (MAbs) to map the antigenic structure of live JEV virus, untreated control virus (UCV), formalin-inactivated commercial vaccine (FICV), and formalin-inactivated virus (FIV). The binding activity of T16 MAb against Nakayama-derived FICV and several strains of FIV was significantly lower compared to live virus and UCV. T16 MAb, a weakly neutralizing JEV serocomplex antibody, was found to inhibit JEV infection at the post-attachment step. The T16 epitope was mapped to amino acids 329, 331, and 389 within domain III (EDIII) of the envelope (E) glycoprotein. When we explored the effect of formalin inactivation on the immunogenicity of JEV, we found that Nakayama-derived FICV, FIV, and UCV all exhibited similar immunogenicity in a mouse model, inducing anti-JEV and anti-EDII 101/106/107 epitope-specific antibodies. However, the EDIII 329/331/389 epitope-specific IgG antibody and neutralizing antibody titers were significantly lower for FICV-immunized and FIV-immunized mouse serum than for UCV-immunized. Formalin inactivation seems to alter the antigenic structure of the E protein, which may reduce the potency of commercially available JEV vaccines. Virus inactivation by H(2)O(2), but not by UV or by short-duration and higher temperature formalin treatment, is able to maintain the antigenic structure of the JEV E protein. Thus, an alternative inactivation method, such as H(2)O(2), which is able to maintain the integrity of the E protein may be essential to improving the potency of inactivated JEV vaccines.",2015 Oct 23,"['Fan, Yi-Chin', 'Chiu, Hsien-Chung', 'Chen, Li-Kuang', 'Chang, Gwong-Jen J.', 'Chiou, Shyan-Song']",PLoS Negl Trop Dis,,,False
b4c0e3c28f1d56b15dc109d4a59731161e07fb41,PMC,Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III,http://dx.doi.org/10.1371/journal.pntd.0004167,PMC4619746,26495991,CC0,"Formalin-inactivated Japanese encephalitis virus (JEV) vaccines are widely available, but the effects of formalin inactivation on the antigenic structure of JEV and the profile of antibodies elicited after vaccination are not well understood. We used a panel of monoclonal antibodies (MAbs) to map the antigenic structure of live JEV virus, untreated control virus (UCV), formalin-inactivated commercial vaccine (FICV), and formalin-inactivated virus (FIV). The binding activity of T16 MAb against Nakayama-derived FICV and several strains of FIV was significantly lower compared to live virus and UCV. T16 MAb, a weakly neutralizing JEV serocomplex antibody, was found to inhibit JEV infection at the post-attachment step. The T16 epitope was mapped to amino acids 329, 331, and 389 within domain III (EDIII) of the envelope (E) glycoprotein. When we explored the effect of formalin inactivation on the immunogenicity of JEV, we found that Nakayama-derived FICV, FIV, and UCV all exhibited similar immunogenicity in a mouse model, inducing anti-JEV and anti-EDII 101/106/107 epitope-specific antibodies. However, the EDIII 329/331/389 epitope-specific IgG antibody and neutralizing antibody titers were significantly lower for FICV-immunized and FIV-immunized mouse serum than for UCV-immunized. Formalin inactivation seems to alter the antigenic structure of the E protein, which may reduce the potency of commercially available JEV vaccines. Virus inactivation by H(2)O(2), but not by UV or by short-duration and higher temperature formalin treatment, is able to maintain the antigenic structure of the JEV E protein. Thus, an alternative inactivation method, such as H(2)O(2), which is able to maintain the integrity of the E protein may be essential to improving the potency of inactivated JEV vaccines.",2015 Oct 23,"['Fan, Yi-Chin', 'Chiu, Hsien-Chung', 'Chen, Li-Kuang', 'Chang, Gwong-Jen J.', 'Chiou, Shyan-Song']",PLoS Negl Trop Dis,,,False
f782959399ba9e5b1f5e79e35c20b62eb765379c,PMC,Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III,http://dx.doi.org/10.1371/journal.pntd.0004167,PMC4619746,26495991,CC0,"Formalin-inactivated Japanese encephalitis virus (JEV) vaccines are widely available, but the effects of formalin inactivation on the antigenic structure of JEV and the profile of antibodies elicited after vaccination are not well understood. We used a panel of monoclonal antibodies (MAbs) to map the antigenic structure of live JEV virus, untreated control virus (UCV), formalin-inactivated commercial vaccine (FICV), and formalin-inactivated virus (FIV). The binding activity of T16 MAb against Nakayama-derived FICV and several strains of FIV was significantly lower compared to live virus and UCV. T16 MAb, a weakly neutralizing JEV serocomplex antibody, was found to inhibit JEV infection at the post-attachment step. The T16 epitope was mapped to amino acids 329, 331, and 389 within domain III (EDIII) of the envelope (E) glycoprotein. When we explored the effect of formalin inactivation on the immunogenicity of JEV, we found that Nakayama-derived FICV, FIV, and UCV all exhibited similar immunogenicity in a mouse model, inducing anti-JEV and anti-EDII 101/106/107 epitope-specific antibodies. However, the EDIII 329/331/389 epitope-specific IgG antibody and neutralizing antibody titers were significantly lower for FICV-immunized and FIV-immunized mouse serum than for UCV-immunized. Formalin inactivation seems to alter the antigenic structure of the E protein, which may reduce the potency of commercially available JEV vaccines. Virus inactivation by H(2)O(2), but not by UV or by short-duration and higher temperature formalin treatment, is able to maintain the antigenic structure of the JEV E protein. Thus, an alternative inactivation method, such as H(2)O(2), which is able to maintain the integrity of the E protein may be essential to improving the potency of inactivated JEV vaccines.",2015 Oct 23,"['Fan, Yi-Chin', 'Chiu, Hsien-Chung', 'Chen, Li-Kuang', 'Chang, Gwong-Jen J.', 'Chiou, Shyan-Song']",PLoS Negl Trop Dis,,,False
a46d2cd0e65ba71e9d1ccf20762c9043ed3e67c2,PMC,Prognosis of nonspecific interstitial pneumonia correlates with perivascular CD4+ T lymphocyte infiltration of the lung,http://dx.doi.org/10.1186/s12890-015-0122-z,PMC4619990,26496721,CC BY,"BACKGROUND: Nonspecific interstitial pneumonia (NSIP) is characterized by interstitial infiltration of T lymphocytes, and subpopulations of these cells may be associated with the progression of fibrosis. However, few studies evaluate the correlation of prognosis with this characteristic. Therefore, we performed morphological and quantitative analyses of T lymphocytes in patients with NSIP and evaluated the relationship between T lymphocytes and prognosis. METHODS: Immunohistochemistry was used to detect the presence of CD4+ and CD8+ T lymphocytes in 55 biopsies of patients with NSIP to determine the numbers of these T cell subpopulations in lymphoid follicles as well as in perivascular, interstitial, and peribronchial anatomical compartments. The relationship between CD4+ and CD8+ T lymphocyte populations and prognosis was analyzed. RESULTS: The mean age of 55 patients was 48.9 ± 10.5 years, and 36 (65 %) of patients were women. All patients were followed for a mean duration of 46 ± 25 months. Thirteen (23.6 %) patients died during follow-up. Perivascular CD4+ lymphocyte infiltration (HR, 0.939; 95 % CI, 0.883–0.999; p = 0.048) was an independent risk factor for survival. Perivascular infiltrates of CD4+ T lymphocytes correlated with survival time (r = 0.270, p = 0.046). Patients with improved forced vital capacity survived longer and had higher numbers of CD4+ T lymphocytes that infiltrated perivascular tissue. The densities of CD4+ and CD8+ T lymphocytes infiltrating other tissues were not significantly associated with survival time. CONCLUSIONS: Perivascular infiltration of CD4+ T lymphocytes in patients with NSIP correlated with prognosis. The underlying mechanisms are unknown and require further studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12890-015-0122-z) contains supplementary material, which is available to authorized users.",2015 Oct 24,"['Qin, Ling', 'Wang, WenZe', 'Liu, HongRui', 'Xiao, Yi', 'Qin, MingWei', 'Zheng, WenJie', 'Shi, JuHong']",BMC Pulm Med,,,True
5c5088ded6a49170c4ee50c8a9bfc5422cc31668,PMC,"Trypsin- and low pH-mediated fusogenicity of avian metapneumovirus fusion proteins is determined by residues at positions 100, 101 and 294",http://dx.doi.org/10.1038/srep15584,PMC4620442,26498473,CC BY,"Avian metapneumovirus (aMPV) and human metapneumovirus (hMPV) are members of the genus Metapneumovirus in the subfamily Pneumovirinae. Metapneumovirus fusion (F) protein mediates the fusion of host cells with the virus membrane for infection. Trypsin- and/or low pH-induced membrane fusion is a strain-dependent phenomenon for hMPV. Here, we demonstrated that three subtypes of aMPV (aMPV/A, aMPV/B, and aMPV/C) F proteins promoted cell-cell fusion in the absence of trypsin. Indeed, in the presence of trypsin, only aMPV/C F protein fusogenicity was enhanced. Mutagenesis of the amino acids at position 100 and/or 101, located at a putative cleavage region in aMPV F proteins, revealed that the trypsin-mediated fusogenicity of aMPV F proteins is regulated by the residues at positions 100 and 101. Moreover, we demonstrated that aMPV/A and aMPV/B F proteins mediated cell-cell fusion independent of low pH, whereas the aMPV/C F protein did not. Mutagenesis of the residue at position 294 in the aMPV/A, aMPV/B, and aMPV/C F proteins showed that 294G played a critical role in F protein-mediated fusion under low pH conditions. These findings on aMPV F protein-induced cell-cell fusion provide new insights into the molecular mechanisms underlying membrane fusion and pathogenesis of aMPV.",2015 Oct 26,"['Yun, Bingling', 'Guan, Xiaolu', 'Liu, Yongzhen', 'Gao, Yanni', 'Wang, Yongqiang', 'Qi, Xiaole', 'Cui, Hongyu', 'Liu, Changjun', 'Zhang, Yanping', 'Gao, Li', 'Li, Kai', 'Gao, Honglei', 'Gao, Yulong', 'Wang, Xiaomei']",Sci Rep,,,True
e96735cc636261d9942b88273a0631b1006ec015,PMC,Remote Activation of Host Cell DNA Synthesis in Uninfected Cells Signaled by Infected Cells in Advance of Virus Transmission,http://dx.doi.org/10.1128/JVI.01950-15,PMC4621119,26311877,CC BY,"Viruses modulate cellular processes and metabolism in diverse ways, but these are almost universally studied in the infected cell itself. Here, we study spatial organization of DNA synthesis during multiround transmission of herpes simplex virus (HSV) using pulse-labeling with ethynyl nucleotides and cycloaddition of azide fluorophores. We report a hitherto unknown and unexpected outcome of virus-host interaction. Consistent with the current understanding of the single-step growth cycle, HSV suppresses host DNA synthesis and promotes viral DNA synthesis in spatially segregated compartments within the cell. In striking contrast, during progressive rounds of infection initiated at a single cell, we observe that infection induces a clear and pronounced stimulation of cellular DNA replication in remote uninfected cells. This induced DNA synthesis was observed in hundreds of uninfected cells at the extended border, outside the perimeter of the progressing infection. Moreover, using pulse-chase analysis, we show that this activation is maintained, resulting in a propagating wave of host DNA synthesis continually in advance of infection. As the virus reaches and infects these activated cells, host DNA synthesis is then shut off and replaced with virus DNA synthesis. Using nonpropagating viruses or conditioned medium, we demonstrate a paracrine effector of uninfected cell DNA synthesis in remote cells continually in advance of infection. These findings have significant implications, likely with broad applicability, for our understanding of the ways in which virus infection manipulates cell processes not only in the infected cell itself but also now in remote uninfected cells, as well as of mechanisms governing host DNA synthesis. IMPORTANCE We show that during infection initiated by a single particle with progressive cell-cell virus transmission (i.e., the normal situation), HSV induces host DNA synthesis in uninfected cells, mediated by a virus-induced paracrine effector. The field has had no conception that this process occurs, and the work changes our interpretation of virus-host interaction during advancing infection and has implications for understanding controls of host DNA synthesis. Our findings demonstrate the utility of chemical biology techniques in analysis of infection processes, reveal distinct processes when infection is examined in multiround transmission versus single-step growth curves, and reveal a hitherto-unknown process in virus infection, likely relevant for other viruses (and other infectious agents) and for remote signaling of other processes, including transcription and protein synthesis.",2015 Aug 26,"['Schmidt, Nora', 'Hennig, Thomas', 'Serwa, Remigiusz A.', 'Marchetti, Magda', ""O'Hare, Peter""]",J Virol,,,False
e622c993d64e1bdcb0b7ec5505945ab5fbe3185e,PMC,Remote Activation of Host Cell DNA Synthesis in Uninfected Cells Signaled by Infected Cells in Advance of Virus Transmission,http://dx.doi.org/10.1128/JVI.01950-15,PMC4621119,26311877,CC BY,"Viruses modulate cellular processes and metabolism in diverse ways, but these are almost universally studied in the infected cell itself. Here, we study spatial organization of DNA synthesis during multiround transmission of herpes simplex virus (HSV) using pulse-labeling with ethynyl nucleotides and cycloaddition of azide fluorophores. We report a hitherto unknown and unexpected outcome of virus-host interaction. Consistent with the current understanding of the single-step growth cycle, HSV suppresses host DNA synthesis and promotes viral DNA synthesis in spatially segregated compartments within the cell. In striking contrast, during progressive rounds of infection initiated at a single cell, we observe that infection induces a clear and pronounced stimulation of cellular DNA replication in remote uninfected cells. This induced DNA synthesis was observed in hundreds of uninfected cells at the extended border, outside the perimeter of the progressing infection. Moreover, using pulse-chase analysis, we show that this activation is maintained, resulting in a propagating wave of host DNA synthesis continually in advance of infection. As the virus reaches and infects these activated cells, host DNA synthesis is then shut off and replaced with virus DNA synthesis. Using nonpropagating viruses or conditioned medium, we demonstrate a paracrine effector of uninfected cell DNA synthesis in remote cells continually in advance of infection. These findings have significant implications, likely with broad applicability, for our understanding of the ways in which virus infection manipulates cell processes not only in the infected cell itself but also now in remote uninfected cells, as well as of mechanisms governing host DNA synthesis. IMPORTANCE We show that during infection initiated by a single particle with progressive cell-cell virus transmission (i.e., the normal situation), HSV induces host DNA synthesis in uninfected cells, mediated by a virus-induced paracrine effector. The field has had no conception that this process occurs, and the work changes our interpretation of virus-host interaction during advancing infection and has implications for understanding controls of host DNA synthesis. Our findings demonstrate the utility of chemical biology techniques in analysis of infection processes, reveal distinct processes when infection is examined in multiround transmission versus single-step growth curves, and reveal a hitherto-unknown process in virus infection, likely relevant for other viruses (and other infectious agents) and for remote signaling of other processes, including transcription and protein synthesis.",2015 Aug 26,"['Schmidt, Nora', 'Hennig, Thomas', 'Serwa, Remigiusz A.', 'Marchetti, Magda', ""O'Hare, Peter""]",J Virol,,,True
c16ef70e46b997661c4aef194fd79c1b902a3c39,PMC,"Do citation trends reflect epidemiologic patterns? Assessing MRSA, emerging and re-emerging pathogens, 1963–2014",http://dx.doi.org/10.1186/s12879-015-1182-7,PMC4621863,26502873,CC BY,"BACKGROUND: A rapid rise in PubMed citations on methicillin-resistant Staphylococcus aureus (MRSA) occurred after 2000, but the relationship of trends in citation to epidemiologic trends for infectious disease is not known. METHODS: We queried PubMed(R), for citations to the following: MRSA, HIV/AIDS, Staphylococcus aureus, severe acute respiratory syndrome, Lyme disease, avian influenza, West Nile virus, Chikungunya, Ebola virus and Middle Eastern respiratory syndrome. Incidence or mortality data were tabulated. RESULTS: We identified 560,225 citations in 1963–2014. There were two distinct qualitative citation patterns. Type I pathogens showed a decade of initial exponential growth. Type II pathogens showed a sudden spike in citations in a year or two, followed by a relative decline. MRSA most closely resembled a Type I pathogen. CONCLUSIONS: The Type I pattern pathogens had varied trends in disease incidence in the years following the exponential growth and subsequent decline in the number of citations. Their differing epidemiologic patterns did not correlate with their pattern of citations. We conclude that citation trends on MRSA cannot be used to determine past epidemiologic trends and also that the citation trend for MRSA in 1995–2011 most closely resembled that for HIV in 1981–1998.",2015 Oct 26,"['Morgan, Ethan', 'David, Michael Z.']",BMC Infect Dis,,,True
f5e971f5c6854bcf76a7963effbbd79e62becab0,PMC,Markedly Elevated Antibody Responses in Wild versus Captive Spotted Hyenas Show that Environmental and Ecological Factors Are Important Modulators of Immunity,http://dx.doi.org/10.1371/journal.pone.0137679,PMC4621877,26444876,CC BY,"Evolutionary processes have shaped the vertebrate immune system over time, but proximal mechanisms control the onset, duration, and intensity of immune responses. Based on testing of the hygiene hypothesis, it is now well known that microbial exposure is important for proper development and regulation of the immune system. However, few studies have examined the differences between wild animals in their natural environments, in which they are typically exposed to a wide array of potential pathogens, and their conspecifics living in captivity. Wild spotted hyenas (Crocuta crocuta) are regularly exposed to myriad pathogens, but there is little evidence of disease-induced mortality in wild hyena populations, suggesting that immune defenses are robust in this species. Here we assessed differences in immune defenses between wild spotted hyenas that inhabit their natural savanna environment and captive hyenas that inhabit a captive environment where pathogen control programs are implemented. Importantly, the captive population of spotted hyenas was derived directly from the wild population and has been in captivity for less than four generations. Our results show that wild hyenas have significantly higher serum antibody concentrations, including total IgG and IgM, natural antibodies, and autoantibodies than do captive hyenas; there was no difference in the bacterial killing capacity of sera collected from captive and wild hyenas. The striking differences in serum antibody concentrations observed here suggest that complementing traditional immunology studies, with comparative studies of wild animals in their natural environment may help to uncover links between environment and immune function, and facilitate progress towards answering immunological questions associated with the hygiene hypothesis.",2015 Oct 7,"['Flies, Andrew S.', 'Mansfield, Linda S.', 'Grant, Chris K.', 'Weldele, Mary L.', 'Holekamp, Kay E.']",PLoS One,,,True
aecb440fc8c84846d96359ffd450f3e24a00cdca,PMC,Redox process is crucial for inhibitory properties of aurintricarboxylic acid against activity of YopH: virulence factor of Yersinia pestis,,PMC4621896,26286963,CC BY,"YopH is a bacterial protein tyrosine phosphatase, which is essential for the viability and pathogenic virulence of the plague-causing Yersinia sp. bacteria. Inactivation of YopH activity would lead to the loss of bacterial pathogenicity. We have studied the inhibitory properties of aurintricarboxylic acid (ATA) against YopH phosphatase and found that at nanomolar concentrations ATA reversibly decreases the activity of YopH. Computational docking studies indicated that in all binding poses ATA binds in the YopH active site. Molecular dynamics simulations showed that in the predicted binding pose, ATA binds to the essential Cys403 and Arg409 residues in the active site and has a stronger binding affinity than the natural substrate (pTyr). The cyclic voltammetry experiments suggest that ATA reacts remarkably strongly with molecular oxygen. Additionally, the electrochemical reduction of ATA in the presence of a negative potential from −2.0 to 2.5 V generates a current signal, which is observed for hydrogen peroxide. Here we showed that ATA indicates a unique mechanism of YopH inactivation due to a redox process. We proposed that the potent inhibitory properties of ATA are a result of its strong binding in the YopH active site and in situ generation of hydrogen peroxide near catalytic cysteine residue.",2015 Jul 22,"['Kuban-Jankowska, Alicja', 'Sahu, Kamlesh K', 'Niedzialkowski, Pawel', 'Gorska, Magdalena', 'Tuszynski, Jack A', 'Ossowski, Tadeusz', 'Wozniak, Michal']",Oncotarget,,,True
1de0f645bef4bb4fa6244abca0b1e0396fdea449,PMC,"Etiology of community acquired pneumonia among children in India: prospective, cohort study",http://dx.doi.org/10.7189/jogh.05.020418,PMC4623579,26528392,CC BY,"BACKGROUND: Childhood community acquired pneumonia (CAP) is a significant problem in developing countries, and confirmation of microbial etiology is important for individual, as well as public health. However, there is paucity of data from a large cohort, examining multiple biological specimens for diverse pathogens (bacteria and viruses). The Community Acquired Pneumonia Etiology Study (CAPES) was designed to address this knowledge gap. METHODS: We enrolled children with CAP (based on WHO IMCI criteria of tachypnea with cough or breathing difficulty) over 24 consecutive months, and recorded presenting symptoms, risk factors, clinical signs, and chest radiography. We performed blood and nasopharyngeal aspirate (NPA) bacterial cultures, and serology (Mycoplasma pneumoniae, Chlamydophila pneumoniae). We also performed multiplex PCR for 25 bacterial/viral species in a subgroup representing 20% of the cohort. Children requiring endotracheal intubation underwent culture and PCR of bronchoalveolar lavage (BAL) specimens. FINDINGS: We enrolled 2345 children. NPA and blood cultures yielded bacteria in only 322 (13.7%) and 49 (2.1%) children respectively. In NPA, Streptococcus pneumoniae (79.1%) predominated, followed by Haemophilus influenzae (9.6%) and Staphylococcus aureus (6.8%). In blood, S. aureus (30.6%) dominated, followed by S. pneumoniae (20.4%) and Klebsiella pneumoniae (12.2%). M. pneumoniae and C. pneumoniae serology were positive in 4.3% and 1.1% respectively. Multiplex PCR in 428 NPA specimens identified organisms in 422 (98.6%); of these 352 (82.2%) had multiple organisms and only 70 (16.4%) had a single organism viz. S. pneumoniae: 35 (50%), Cytomegalovirus (CMV): 13 (18.6%), Respiratory Syncytial Virus (RSV): 9 (12.9%), other viruses: 6 (8.7%), S. aureus: 5 (7.1%), and H. influenzae: 2 (2.9%). BAL PCR (n = 30) identified single pathogens in 10 (S. pneumoniae–3, CMV–3, S. aureus–2, H. influenzae–2) and multiple pathogens in 18 children. There were 108 (4.6%) deaths. The pattern of pathogens identified did not correlate with pneumonia severity or mortality. CONCLUSIONS: The majority of children with CAP have multiple pathogens (bacteria and viruses). S. pneumoniae and S. aureus predominate in NPA and blood respectively. CMV and RSV were the dominant respiratory viruses in NPA and BAL. The presence of multiple pathogens, especially organisms associated with nasopharyngeal carriage, precludes confirmation of a causal relationship in most cases.",,"['Mathew, Joseph L.', 'Singhi, Sunit', 'Ray, Pallab', 'Hagel, Eva', 'Saghafian–Hedengren, Shanie', 'Bansal, Arun', 'Ygberg, Sofia', 'Sodhi, Kushaljit Singh', 'Kumar, B V Ravi', 'Nilsson, Anna']",J Glob Health.; 5(2):050418,,,True
aab34a745e83e2357628908ba583ef703632993d,PMC,"Etiology of community acquired pneumonia among children in India: prospective, cohort study",http://dx.doi.org/10.7189/jogh.05.020418,PMC4623579,26528392,CC BY,"BACKGROUND: Childhood community acquired pneumonia (CAP) is a significant problem in developing countries, and confirmation of microbial etiology is important for individual, as well as public health. However, there is paucity of data from a large cohort, examining multiple biological specimens for diverse pathogens (bacteria and viruses). The Community Acquired Pneumonia Etiology Study (CAPES) was designed to address this knowledge gap. METHODS: We enrolled children with CAP (based on WHO IMCI criteria of tachypnea with cough or breathing difficulty) over 24 consecutive months, and recorded presenting symptoms, risk factors, clinical signs, and chest radiography. We performed blood and nasopharyngeal aspirate (NPA) bacterial cultures, and serology (Mycoplasma pneumoniae, Chlamydophila pneumoniae). We also performed multiplex PCR for 25 bacterial/viral species in a subgroup representing 20% of the cohort. Children requiring endotracheal intubation underwent culture and PCR of bronchoalveolar lavage (BAL) specimens. FINDINGS: We enrolled 2345 children. NPA and blood cultures yielded bacteria in only 322 (13.7%) and 49 (2.1%) children respectively. In NPA, Streptococcus pneumoniae (79.1%) predominated, followed by Haemophilus influenzae (9.6%) and Staphylococcus aureus (6.8%). In blood, S. aureus (30.6%) dominated, followed by S. pneumoniae (20.4%) and Klebsiella pneumoniae (12.2%). M. pneumoniae and C. pneumoniae serology were positive in 4.3% and 1.1% respectively. Multiplex PCR in 428 NPA specimens identified organisms in 422 (98.6%); of these 352 (82.2%) had multiple organisms and only 70 (16.4%) had a single organism viz. S. pneumoniae: 35 (50%), Cytomegalovirus (CMV): 13 (18.6%), Respiratory Syncytial Virus (RSV): 9 (12.9%), other viruses: 6 (8.7%), S. aureus: 5 (7.1%), and H. influenzae: 2 (2.9%). BAL PCR (n = 30) identified single pathogens in 10 (S. pneumoniae–3, CMV–3, S. aureus–2, H. influenzae–2) and multiple pathogens in 18 children. There were 108 (4.6%) deaths. The pattern of pathogens identified did not correlate with pneumonia severity or mortality. CONCLUSIONS: The majority of children with CAP have multiple pathogens (bacteria and viruses). S. pneumoniae and S. aureus predominate in NPA and blood respectively. CMV and RSV were the dominant respiratory viruses in NPA and BAL. The presence of multiple pathogens, especially organisms associated with nasopharyngeal carriage, precludes confirmation of a causal relationship in most cases.",,"['Mathew, Joseph L.', 'Singhi, Sunit', 'Ray, Pallab', 'Hagel, Eva', 'Saghafian–Hedengren, Shanie', 'Bansal, Arun', 'Ygberg, Sofia', 'Sodhi, Kushaljit Singh', 'Kumar, B V Ravi', 'Nilsson, Anna']",J Glob Health.; 5(2):050418,,,False
b9a74f1f03a9b75351badb02e13448d1f65f7ed8,PMC,Inferring Infection Patterns Based on a Connectivity Map of Host Transcriptional Responses,http://dx.doi.org/10.1038/srep15820,PMC4623713,26508266,CC BY,"Host responses to infections represent an important pathogenicity determiner, and delineation of host responses can elucidate pathogenesis processes and inform the development of anti-infection therapies. Low cost, high throughput, easy quantitation, and rich descriptions have made gene expression profiling generated by DNA microarrays an optimal approach for describing host transcriptional responses (HTRs). However, efforts to characterize the landscape of HTRs to diverse pathogens are far from offering a comprehensive view. Here, we developed an HTR Connectivity Map based on systematic assessment of pairwise similarities of HTRs to 50 clinically important human pathogens using 1353 gene-expression profiles generated from >60 human cells/tissues. These 50 pathogens were further partitioned into eight robust “HTR communities” (i.e., groups with more consensus internal HTR similarities). These communities showed enrichment in specific infection attributes and differential gene expression patterns. Using query signatures of HTRs to external pathogens, we demonstrated four distinct modes of HTR associations among different pathogens types/class, and validated the reliability of the HTR community divisions for differentiating and categorizing pathogens from a host-oriented perspective. These findings provide a first-generation HTR Connectivity Map of 50 diverse pathogens, and demonstrate the potential for using annotated HTR community to detect functional associations among infectious pathogens.",2015 Oct 28,"['Han, Lu', 'He, Haochen', 'Li, Fei', 'Cui, Xiuliang', 'Xie, Dafei', 'Liu, Yang', 'Zheng, Xiaofei', 'Bai, Hui', 'Wang, Shengqi', 'Bo, Xiaochen']",Sci Rep,,,True
a4fe6d2a7e5129ad14c0af09390a13fdacdb01ee,PMC,Inferring Infection Patterns Based on a Connectivity Map of Host Transcriptional Responses,http://dx.doi.org/10.1038/srep15820,PMC4623713,26508266,CC BY,"Host responses to infections represent an important pathogenicity determiner, and delineation of host responses can elucidate pathogenesis processes and inform the development of anti-infection therapies. Low cost, high throughput, easy quantitation, and rich descriptions have made gene expression profiling generated by DNA microarrays an optimal approach for describing host transcriptional responses (HTRs). However, efforts to characterize the landscape of HTRs to diverse pathogens are far from offering a comprehensive view. Here, we developed an HTR Connectivity Map based on systematic assessment of pairwise similarities of HTRs to 50 clinically important human pathogens using 1353 gene-expression profiles generated from >60 human cells/tissues. These 50 pathogens were further partitioned into eight robust “HTR communities” (i.e., groups with more consensus internal HTR similarities). These communities showed enrichment in specific infection attributes and differential gene expression patterns. Using query signatures of HTRs to external pathogens, we demonstrated four distinct modes of HTR associations among different pathogens types/class, and validated the reliability of the HTR community divisions for differentiating and categorizing pathogens from a host-oriented perspective. These findings provide a first-generation HTR Connectivity Map of 50 diverse pathogens, and demonstrate the potential for using annotated HTR community to detect functional associations among infectious pathogens.",2015 Oct 28,"['Han, Lu', 'He, Haochen', 'Li, Fei', 'Cui, Xiuliang', 'Xie, Dafei', 'Liu, Yang', 'Zheng, Xiaofei', 'Bai, Hui', 'Wang, Shengqi', 'Bo, Xiaochen']",Sci Rep,,,False
8bb5f822c7bae1c50b1d5b7a9da329a1f9d8aee2,PMC,Transcriptomic Changes Due to Cytoplasmic TDP-43 Expression Reveal Dysregulation of Histone Transcripts and Nuclear Chromatin,http://dx.doi.org/10.1371/journal.pone.0141836,PMC4624943,26510133,CC BY,"TAR DNA-binding protein 43 (TDP-43) is normally a nuclear RNA-binding protein that exhibits a range of functions including regulation of alternative splicing, RNA trafficking, and RNA stability. However, in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), TDP-43 is abnormally phosphorylated, ubiquitinated, and cleaved, and is mislocalized to the cytoplasm where it forms distinctive aggregates. We previously developed a mouse model expressing human TDP-43 with a mutation in its nuclear localization signal (ΔNLS-hTDP-43) so that the protein preferentially localizes to the cytoplasm. These mice did not exhibit a significant number of cytoplasmic aggregates, but did display dramatic changes in gene expression as measured by microarray, suggesting that cytoplasmic TDP-43 may be associated with a toxic gain-of-function. Here, we analyze new RNA-sequencing data from the ΔNLS-hTDP-43 mouse model, together with published RNA-sequencing data obtained previously from TDP-43 antisense oligonucleotide (ASO) knockdown mice to investigate further the dysregulation of gene expression in the ΔNLS model. This analysis reveals that the transcriptomic effects of the overexpression of the ΔNLS-hTDP-43 transgene are likely due to a gain of cytoplasmic function. Moreover, cytoplasmic TDP-43 expression alters transcripts that regulate chromatin assembly, the nucleolus, lysosomal function, and histone 3’ untranslated region (UTR) processing. These transcriptomic alterations correlate with observed histologic abnormalities in heterochromatin structure and nuclear size in transgenic mouse and human brains.",2015 Oct 28,"['Amlie-Wolf, Alexandre', 'Ryvkin, Paul', 'Tong, Rui', 'Dragomir, Isabelle', 'Suh, EunRan', 'Xu, Yan', 'Van Deerlin, Vivianna M.', 'Gregory, Brian D.', 'Kwong, Linda K.', 'Trojanowski, John Q.', 'Lee, Virginia M.-Y.', 'Wang, Li-San', 'Lee, Edward B.']",PLoS One,,,True
3811a68dda2911cb406a2fbb448530aa2319ee21,PMC,Mucosal Immunogenicity of Genetically Modified Lactobacillus acidophilus Expressing an HIV-1 Epitope within the Surface Layer Protein,http://dx.doi.org/10.1371/journal.pone.0141713,PMC4624987,26509697,CC BY,"Surface layer proteins of probiotic lactobacilli are theoretically efficient epitope-displaying scaffolds for oral vaccine delivery due to their high expression levels and surface localization. In this study, we constructed genetically modified Lactobacillus acidophilus strains expressing the membrane proximal external region (MPER) from human immunodeficiency virus type 1 (HIV-1) within the context of the major S-layer protein, SlpA. Intragastric immunization of mice with the recombinants induced MPER-specific and S-layer protein-specific antibodies in serum and mucosal secretions. Moreover, analysis of systemic SlpA-specific cytokines revealed that the responses appeared to be Th1 and Th17 dominant. These findings demonstrated the potential use of the Lactobacillus S-layer protein for development of oral vaccines targeting specific peptides.",2015 Oct 28,"['Kajikawa, Akinobu', 'Zhang, Lin', 'LaVoy, Alora', 'Bumgardner, Sara', 'Klaenhammer, Todd R.', 'Dean, Gregg A.']",PLoS One,,,True
a65b8907068dde79fb7cc6e885a745607ed1f371,PMC,Vaccination Method Affects Immune Response and Bacterial Growth but Not Protection in the Salmonella Typhimurium Animal Model of Typhoid,http://dx.doi.org/10.1371/journal.pone.0141356,PMC4625024,26509599,CC BY,"Understanding immune responses elicited by vaccines, together with immune responses required for protection, is fundamental to designing effective vaccines and immunisation programs. This study examines the effects of the route of administration of a live attenuated vaccine on its interactions with, and stimulation of, the murine immune system as well as its ability to increase survival and provide protection from colonisation by a virulent challenge strain. We assess the effect of administration method using the murine model for typhoid, where animals are infected with S. Typhimurium. Mice were vaccinated either intravenously or orally with the same live attenuated S. Typhimurium strain and data were collected on vaccine strain growth, shedding and stimulation of antibodies and cytokines. Following vaccination, mice were challenged with a virulent strain of S. Typhimurium and the protection conferred by the different vaccination routes was measured in terms of challenge suppression and animal survival. The main difference in immune stimulation found in this study was the development of a secretory IgA response in orally-vaccinated mice, which was absent in IV vaccinated mice. While both strains showed similar protection in terms of challenge suppression in systemic organs (spleen and liver) as well as survival, they differed in terms of challenge suppression of virulent pathogens in gut-associated organs. This difference in gut colonisation presents important questions around the ability of vaccines to prevent shedding and transmission. These findings demonstrate that while protection conferred by two vaccines can appear to be the same, the mechanisms controlling the protection can differ and have important implications for infection dynamics within a population.",2015 Oct 28,"['Kinnear, Clare L.', 'Strugnell, Richard A.']",PLoS One,,,True
892fc12b9b9b6cf0030efee835b76a5c7879f0c2,PMC,An optimised method for the production of MERS-CoV spike expressing viral pseudotypes,http://dx.doi.org/10.1016/j.mex.2015.09.003,PMC4625112,26587388,CC BY,"The production and use of pseudotyped viral particles are widely established for many viruses, and applications in the fields of serology and vaccine development are manifold. Viral pseudotypes have proven to be powerful tools to study the effects of viral evolution on serological outcomes, viral tropism and immunogenicity studies. Pseudotyped viruses are chimeric constructs in which the outer (surface) glycoprotein(s) of one virus is combined with the replication-defective viral “core” of another virus. Pseudotypes allow for accurate, sequence-directed, sensitive antibody neutralisation assays and antiviral screening to be conducted within a low biosecurity facility and offer a safe and efficient alternative to wildtype virus use. The protocol outlined here represents a rapid and reliable method for the generation of high-titre pseudotype viral particles with the MERS-CoV spike protein on a lentiviral core, and is adapted from previously published protocols. This protocol is optimised for transfection in a 100 mm Petri dish with 7 ml of supernatant harvested, however it can be readily scaled to different production volumes. This protocol has a number of advantages including: • Use of readily available reagents. • Consistent, high virus titres. • Rapid generation of novel glycoproteins for research into strain variation.",2015 Oct 13,"['Grehan, K.', 'Ferrara, F.', 'Temperton, N.']",MethodsX,,,False
696e87c58213d9b59cac6ecc3c695a245772b081,PMC,Detection of immunoglobulin (Ig) A antibodies against porcine epidemic diarrhea virus (PEDV) in fecal and serum samples,http://dx.doi.org/10.1016/j.mex.2015.10.001,PMC4625113,26587386,CC BY,"Many assays for detection of antibodies against porcine epidemic diarrhea virus (PEDV) are based on detection of neutralizing antibodies or immunoglobulin (Ig) G in serum samples. However, due to the particular features of the mucosal immune system, presence of serum antibodies against enteric pathogens, such as PEDV, not always correlates with protection. In contrast, anti-PEDV IgA antibodies correlate with protection against subsequent challenges. An indirect PEDV IgA ELISA was previously developed to monitor IgA levels in colostrum and milk samples. In the present paper we describe an adaptation of the protocol for detection of IgA antibodies in serum and fecal samples. • The adapted protocol will aid in future assessment of protective levels of humoral response against PEDV infection by measuring IgA levels in serum and fecal samples. • Fecal samples are non-invasive and easy to collect at any time by animal caretakers and therefore offering advantages over the serum sample collection procedure. • A strong positive correlation between the anti-PEDV levels in fecal and serum samples was identified; however, detection of IgA antibodies was often more successful in serum than in paired fecal samples due to overall lower sample-to-positive (S/P) ratios for the latter sample type.",2015 Oct 13,"['Gerber, Priscilla F.', 'Opriessnig, Tanja']",MethodsX,,,False
67c9acbf8204919fe540d58d7db296b9210f1e90,PMC,Throat and nasal swabs for molecular detection of respiratory viruses in acute pharyngitis,http://dx.doi.org/10.1186/s12985-015-0408-z,PMC4625558,26511714,CC BY,"BACKGROUND: Detection of specific respiratory viruses is important for surveillance programs, where nasopharyngeal or nasal swabs have traditionally been used. Our objective was to determine whether sampling with a throat swab provides incremental benefit—when used in conjunction with a nasal swab—to detect respiratory viruses among patients with acute pharyngitis in the outpatient setting. FINDINGS: Among 83 university students with acute pharyngitis, we detected respiratory viruses with molecular assays on two samples collected per student: with a flocked nasal mid-turbinate swab and a rayon throat swab. Forty-eight (58 %) patients had virus-positive samples, with 49 virus positives detected by either swab (one patient had a dual viral co-infection). The most common viruses were rhinovirus, coronavirus, and influenza A virus. Specifically, 29 virus positives were detected by both swabs, 14 exclusively by the nasal swab, and six exclusively by the throat swab. The additional six virus positives detected by the throat swab corresponded to an absolute increase in viral detection of 7.1 % (95 % CI: 1.2–12.9 %); the specific viruses detected were four rhinoviruses and two coronaviruses. CONCLUSIONS: The flocked nasal swab samples respiratory viruses well, even among patients whose primary complaint is a sore throat. The rayon throat swab has modest incremental value over and above using the flocked nasal mid-turbinate swab alone, which suggests that while throat swabs alone would not be adequate for respiratory viral surveillance, they may have value as a supplementary test.",2015 Oct 29,"['Ali, Mohsin', 'Han, Sangsu', 'Gunst, Chris J.', 'Lim, Steve', 'Luinstra, Kathy', 'Smieja, Marek']",Virol J,,,True
ad79f4149f66651ceee0f251347fc5093294f68d,PMC,Multifunctional roles of leader protein of foot-and-mouth disease viruses in suppressing host antiviral responses,http://dx.doi.org/10.1186/s13567-015-0273-1,PMC4625562,26511922,CC BY,"Foot-and-mouth disease virus (FMDV) leader protein (L(pro)) is a papain-like proteinase, which plays an important role in FMDV pathogenesis. L(pro) exists as two forms, Lab and Lb, due to translation being initiated from two different start codons separated by 84 nucleotides. L(pro) self-cleaves from the nascent viral polyprotein precursor as the first mature viral protein. In addition to its role as a viral proteinase, L(pro) also has the ability to antagonize host antiviral effects. To promote FMDV replication, L(pro) can suppress host antiviral responses by three different mechanisms: (1) cleavage of eukaryotic translation initiation factor 4 γ (eIF4G) to shut off host protein synthesis; (2) inhibition of host innate immune responses through restriction of interferon-α/β production; and (3) L(pro) can also act as a deubiquitinase and catalyze deubiquitination of innate immune signaling molecules. In the light of recent functional and biochemical findings regarding L(pro), this review introduces the basic properties of L(pro) and the mechanisms by which it antagonizes host antiviral responses.",2015 Oct 28,"['Liu, Yingqi', 'Zhu, Zixiang', 'Zhang, Miaotao', 'Zheng, Haixue']",Vet Res,,,True
fd1b26543d016107178798ed466d39ecfe4572cc,PMC,Development of a rapid recombinase polymerase amplification assay for the detection of Streptococcus pneumoniae in whole blood,http://dx.doi.org/10.1186/s12879-015-1212-5,PMC4625855,26515409,CC BY,"BACKGROUND: Streptococcus pneumoniae is an important cause of microbial disease in humans. The introduction of multivalent vaccines has coincided with a dramatic decrease in the number of pneumococcal-related deaths. In spite of this, at a global level, pneumococcal infection remains an important cause of death among children under 5 years of age and in adults 65 years of age or older. In order to properly manage patients and control the spread of infection, a rapid and highly sensitive diagnostic method is needed for routine implementation, especially in resource-limited regions where pneumococcal disease is most prevalent. METHODS: Using the gene encoding leader peptidase A as a molecular diagnostics target, a real-time RPA assay was designed and optimised for the detection of S. pneumoniae in whole blood. The performance of the assay was compared to real-time PCR in terms of its analytical limit of detection and specificity. The inhibitory effect of human genomic DNA on amplification was investigated. The potential clinical utility of the assay was investigated using a small number of clinical samples. RESULTS: The RPA assay has a limit of detection equivalent to PCR (4.0 and 5.1 genome equivalents per reaction, respectively) and was capable of detecting the equivalent of <1 colony forming unit of S. pneumoniae when spiked into human whole blood. The RPA assay was 100 % inclusive (38/38 laboratory reference strains and 19/19 invasive clinical isolates) and 100 % exclusive; differentiating strains of S. pneumoniae species from other viridans group streptococci, including S. pseudopneumoniae. When applied to the analysis of a small number (n = 11) of clinical samples (blood culture positive for S. pneumoniae), the RPA assay was demonstrated to be both rapid and sensitive. CONCLUSIONS: The RPA assay developed in this work is shown to be as sensitive and as specific as PCR. In terms of reaction kinetics, the RPA assay is shown to exceed those of the PCR, with the RPA running to completion in 20 minutes and capable generating a positive signal in as little as 6 minutes. This work represents a potentially suitable assay for application in point-of-care settings.",2015 Oct 29,"['Clancy, Eoin', 'Higgins, Owen', 'Forrest, Matthew S.', 'Boo, Teck Wee', 'Cormican, Martin', 'Barry, Thomas', 'Piepenburg, Olaf', 'Smith, Terry J.']",BMC Infect Dis,,,True
4c76e1e9a4f5afc01accd2dbbd43f0463744e8d2,PMC,Effectively Communicating the Uncertainties Surrounding Ebola Virus Transmission,http://dx.doi.org/10.1371/journal.ppat.1005097,PMC4626028,26512988,CC BY,"The current Ebola virus outbreak has highlighted the uncertainties surrounding many aspects of Ebola virus virology, including routes of transmission. The scientific community played a leading role during the outbreak—potentially, the largest of its kind—as many of the questions surrounding ebolaviruses have only been interrogated in the laboratory. Scientists provided an invaluable resource for clinicians, public health officials, policy makers, and the lay public in understanding the progress of Ebola virus disease and the continuing outbreak. Not all of the scientific communication, however, was accurate or effective. There were multiple instances of published articles during the height of the outbreak containing potentially misleading scientific language that spurred media overreaction and potentially jeopardized preparedness and policy decisions at critical points. Here, we use articles declaring the potential for airborne transmission of Ebola virus as a case study in the inaccurate reporting of basic science, and we provide recommendations for improving the communication about unknown aspects of disease during public health crises.",2015 Oct 29,"['Kilianski, Andy', 'Evans, Nicholas G.']",PLoS Pathog,,,True
87c6c45d9946889a9a3551b31adff4c32c6c237e,PMC,Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine,http://dx.doi.org/10.1371/journal.ppat.1005215,PMC4626112,26513244,CC BY,"A SARS-CoV lacking the full-length E gene (SARS-CoV-∆E) was attenuated and an effective vaccine. Here, we show that this mutant virus regained fitness after serial passages in cell culture or in vivo, resulting in the partial duplication of the membrane gene or in the insertion of a new sequence in gene 8a, respectively. The chimeric proteins generated in cell culture increased virus fitness in vitro but remained attenuated in mice. In contrast, during SARS-CoV-∆E passage in mice, the virus incorporated a mutated variant of 8a protein, resulting in reversion to a virulent phenotype. When the full-length E protein was deleted or its PDZ-binding motif (PBM) was mutated, the revertant viruses either incorporated a novel chimeric protein with a PBM or restored the sequence of the PBM on the E protein, respectively. Similarly, after passage in mice, SARS-CoV-∆E protein 8a mutated, to now encode a PBM, and also regained virulence. These data indicated that the virus requires a PBM on a transmembrane protein to compensate for removal of this motif from the E protein. To increase the genetic stability of the vaccine candidate, we introduced small attenuating deletions in E gene that did not affect the endogenous PBM, preventing the incorporation of novel chimeric proteins in the virus genome. In addition, to increase vaccine biosafety, we introduced additional attenuating mutations into the nsp1 protein. Deletions in the carboxy-terminal region of nsp1 protein led to higher host interferon responses and virus attenuation. Recombinant viruses including attenuating mutations in E and nsp1 genes maintained their attenuation after passage in vitro and in vivo. Further, these viruses fully protected mice against challenge with the lethal parental virus, and are therefore safe and stable vaccine candidates for protection against SARS-CoV.",2015 Oct 29,"['Jimenez-Guardeño, Jose M.', 'Regla-Nava, Jose A.', 'Nieto-Torres, Jose L.', 'DeDiego, Marta L.', 'Castaño-Rodriguez, Carlos', 'Fernandez-Delgado, Raul', 'Perlman, Stanley', 'Enjuanes, Luis']",PLoS Pathog,,,True
67bd507b6486d95e40e4f1435d45efd6421267c9,PMC,Full-Length Genome Characterization of Chinese Porcine Deltacoronavirus Strain CH/SXD1/2015,http://dx.doi.org/10.1128/genomeA.01284-15,PMC4626615,26514769,CC BY,A porcine deltacoronavirus (PDCoV) was identified in the Chinese mainland and found to be closely related to Hong Kong strain HKU15-155 but differed from PDCoV strains in the United States and South Korea. The complete genome of PDCoV strain CH/SXD1/201 was sequenced and analyzed to further characterize PDCoV in Chinese swine.,2015 Oct 29,"['Chen, Fangzhou', 'Zhu, Yinxing', 'Wu, Meizhou', 'Ku, Xugang', 'Yao, Li', 'He, Qigai']",Genome Announc,,,True
0a4f30f5fd02ad89dc9ba18964325c6738807465,PMC,Middle East Respiratory Syndrome and Medical Students: Letter from China,http://dx.doi.org/10.3390/ijerph121013289,PMC4627031,26512679,CC BY,Objectives: The present study aimed to investigate the knowledge of Middle East Respiratory Syndrome (MERS) among Chinese medical students. Methods: A structured questionnaire on MERS was conducted among 214 medical students in China. Results: The average correction of the single question varied from 36.0% to 89.7%. There is a significant difference on MERS knowledge among different majors of medical students (p < 0.05). Management students scored significantly higher than students of other majors (p < 0.05). Conclusion: Chinese medical students had good knowledge of MERS. The MERS knowledge score varied among students of different majors. Education on disease control should be included in the school curriculum.,2015 Oct 23,"['Liu, Mengxue', 'Jiang, Chengsheng', 'Donovan, Connor', 'Wen, Yufeng', 'Wenjie, Sun']",Int J Environ Res Public Health,,,True
053aa0c7280e2bb41a033cb0ae7c0d6bd07afc40,PMC,The role of wobble uridine modifications in +1 translational frameshifting in eukaryotes,http://dx.doi.org/10.1093/nar/gkv832,PMC4627075,26283182,CC BY,"In Saccharomyces cerevisiae, 11 out of 42 tRNA species contain 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U), 5-methoxycarbonylmethyluridine (mcm(5)U), 5-carbamoylmethyluridine (ncm(5)U) or 5-carbamoylmethyl-2′-O-methyluridine (ncm(5)Um) nucleosides in the anticodon at the wobble position (U(34)). Earlier we showed that mutants unable to form the side chain at position 5 (ncm(5) or mcm(5)) or lacking sulphur at position 2 (s(2)) of U(34) result in pleiotropic phenotypes, which are all suppressed by overexpression of hypomodified tRNAs. This observation suggests that the observed phenotypes are due to inefficient reading of cognate codons or an increased frameshifting. The latter may be caused by a ternary complex (aminoacyl-tRNA*eEF1A*GTP) with a modification deficient tRNA inefficiently being accepted to the ribosomal A-site and thereby allowing an increased peptidyl-tRNA slippage and thus a frameshift error. In this study, we have investigated the role of wobble uridine modifications in reading frame maintenance, using either the Renilla/Firefly luciferase bicistronic reporter system or a modified Ty1 frameshifting site in a HIS4A::lacZ reporter system. We here show that the presence of mcm(5) and s(2) side groups at wobble uridines are important for reading frame maintenance and thus the aforementioned mutant phenotypes might partly be due to frameshift errors.",2015 Oct 30,"['Tükenmez, Hasan', 'Xu, Hao', 'Esberg, Anders', 'Byström, Anders S.']",Nucleic Acids Res,,,True
a7106903388d10421825d62d03144d48cc5a3bd9,PMC,The role of wobble uridine modifications in +1 translational frameshifting in eukaryotes,http://dx.doi.org/10.1093/nar/gkv832,PMC4627075,26283182,CC BY,"In Saccharomyces cerevisiae, 11 out of 42 tRNA species contain 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U), 5-methoxycarbonylmethyluridine (mcm(5)U), 5-carbamoylmethyluridine (ncm(5)U) or 5-carbamoylmethyl-2′-O-methyluridine (ncm(5)Um) nucleosides in the anticodon at the wobble position (U(34)). Earlier we showed that mutants unable to form the side chain at position 5 (ncm(5) or mcm(5)) or lacking sulphur at position 2 (s(2)) of U(34) result in pleiotropic phenotypes, which are all suppressed by overexpression of hypomodified tRNAs. This observation suggests that the observed phenotypes are due to inefficient reading of cognate codons or an increased frameshifting. The latter may be caused by a ternary complex (aminoacyl-tRNA*eEF1A*GTP) with a modification deficient tRNA inefficiently being accepted to the ribosomal A-site and thereby allowing an increased peptidyl-tRNA slippage and thus a frameshift error. In this study, we have investigated the role of wobble uridine modifications in reading frame maintenance, using either the Renilla/Firefly luciferase bicistronic reporter system or a modified Ty1 frameshifting site in a HIS4A::lacZ reporter system. We here show that the presence of mcm(5) and s(2) side groups at wobble uridines are important for reading frame maintenance and thus the aforementioned mutant phenotypes might partly be due to frameshift errors.",2015 Oct 30,"['Tükenmez, Hasan', 'Xu, Hao', 'Esberg, Anders', 'Byström, Anders S.']",Nucleic Acids Res,,,False
ec7ab79619e983bb78f09c3b72c0cd36ea2f4924,PMC,Dual Mutation Events in the Haemagglutinin-Esterase and Fusion Protein from an Infectious Salmon Anaemia Virus HPR0 Genotype Promote Viral Fusion and Activation by an Ubiquitous Host Protease,http://dx.doi.org/10.1371/journal.pone.0142020,PMC4627773,26517828,CC BY,"In Infectious salmon anaemia virus (ISAV), deletions in the highly polymorphic region (HPR) in the near membrane domain of the haemagglutinin-esterase (HE) stalk, influence viral fusion. It is suspected that selected mutations in the associated Fusion (F) protein may also be important in regulating fusion activity. To better understand the underlying mechanisms involved in ISAV fusion, several mutated F proteins were generated from the Scottish Nevis and Norwegian SK779/06 HPR0. Co-transfection with constructs encoding HE and F were performed, fusion activity assessed by content mixing assay and the degree of proteolytic cleavage by western blot. Substitutions in Nevis F demonstrated that K276 was the most likely cleavage site in the protein. Furthermore, amino acid substitutions at three sites and two insertions, all slightly upstream of K276, increased fusion activity. Co-expression with HE harbouring a full-length HPR produced high fusion activities when trypsin and low pH were applied. In comparison, under normal culture conditions, groups containing a mutated HE with an HPR deletion were able to generate moderate fusion levels, while those with a full length HPR HE could not induce fusion. This suggested that HPR length may influence how the HE primes the F protein and promotes fusion activation by an ubiquitous host protease and/or facilitate subsequent post-cleavage refolding steps. Variations in fusion activity through accumulated mutations on surface glycoproteins have also been reported in other orthomyxoviruses and paramyxoviruses. This may in part contribute to the different virulence and tissue tropism reported for HPR0 and HPR deleted ISAV genotypes.",2015 Oct 30,"['Fourrier, Mickael', 'Lester, Katherine', 'Markussen, Turhan', 'Falk, Knut', 'Secombes, Christopher J.', 'McBeath, Alastair', 'Collet, Bertrand']",PLoS One,,,True
2a40cae1982703e2b3f357d3721982eef57e0258,PMC,Is There Any Role of Inhalational Corticosteroids in the Prophylaxis of Post-Traumatic Fat Embolism Syndrome?,http://dx.doi.org/10.7759/cureus.332,PMC4627829,26543690,CC BY,"Fat embolism syndrome (FES) is primarily a lung parenchymal disorder resulting from interstitial and alveolar inflammation triggered by the lipid metabolites in blood circulation. The 'low-dose' corticosteroid is supposed to have a prophylactic effect on the incidence of the FES and arterial hypoxemia by reducing this inflammatory response. It is expected that inhaled corticosteroids (ciclesonide aerosol) may prevent the development of hypoxemia or fat embolism syndrome in high-risk patients by reducing this inflammatory response. Metered-dose inhaler (MDI) steroid preparations can reach the lung parenchyma with minimal systemic effect. Sixty cases of polytrauma patients presenting within eight hours of injury were randomly allocated into one of the two groups. In Group 1 (n(1)=30) ciclesonide, 640 mcg, was given with a metered dose inhaler and repeated once again after 24 hours, whereas Group 2 (n(2)=30) was taken as control and observed for 72 hours for any episode of hypoxia. The outcome was assessed using Schonfeld’s criteria for the eventual outcome of subclinical or clinical FES. Out of 30 patients in each group, six patients developed subclinical FES, whereas three from ciclesonide prophylaxis group and eight from controls developed clinical FES. There is no statistical significance found between the eventual outcomes of subclinical or clinical FES between the ciclesonide prophylaxis and control group. Although there was a trend seen in the possible preventive efficacy of inhalational steroid in the present study, it did not reach the statistically significant level. The prophylactic role of inhalational steroid in post-traumatic subclinical and clinical FES is statistically insignificant in the present study.",,"['Agarwal, Amit Kumar', 'Sen, Ramesh', 'Tripathy, Sujit K', 'Aggarwal, Sameer', 'G., Nirmalraj', 'Gupta, Dheeraj']",Cureus.; 7(9):e332,,,True
5a63186e3d015f0bb7378218ebd26b96f7bae63e,PMC,Emergency management training in Korea: combining and balancing supply- and demand-centered paradigms,http://dx.doi.org/10.1186/s40064-015-1459-8,PMC4628130,26543787,CC BY,"This article aims to encourage NEMA (or newly named as MPSS) to combine its supply-centered paradigm with a newly proposed “demand-centered paradigm” in the Korean field of emergency management training (EMT). Based on qualitative content analysis, this paper defined the current field of EMT to be a supply-centered paradigm via three components: locations, courses, and participants. This paradigm focuses on EMT provision as supplied and dictated by the national government. On the other hand, a demand-centered model is about looking into stakeholders’ actual needs for EMT. In this regard, alternatives with reference to the demand-centered paradigm via the same three components were discussed and considered. The key tenet is that having revealed that NEMA has unequivocally focused on the results side or effectiveness of EMT via a supply-centered paradigm, Korea should address and consider the same three components, this time by fusing and incorporating a fair process of EMT by enlisting active roles from the local community, academic scholars, and civilian training attendees in a demand-centered paradigm.",2015 Oct 29,"['Ha, Kyoo-Man', 'Park, Sosoon', 'Yoon, Yi', 'Nam, Ki-Hun', 'Oh, Hyeon-Mun']",Springerplus,,,True
389053111a32e148f8b7c07c883818f70525aa73,PMC,Integrated micro-optofluidic platform for real-time detection of airborne microorganisms,http://dx.doi.org/10.1038/srep15983,PMC4629162,26522006,CC BY,"We demonstrate an integrated micro-optofluidic platform for real-time, continuous detection and quantification of airborne microorganisms. Measurements of the fluorescence and light scattering from single particles in a microfluidic channel are used to determine the total particle number concentration and the microorganism number concentration in real-time. The system performance is examined by evaluating standard particle measurements with various sample flow rates and the ratios of fluorescent to non-fluorescent particles. To apply this method to real-time detection of airborne microorganisms, airborne Escherichia coli, Bacillus subtilis, and Staphylococcus epidermidis cells were introduced into the micro-optofluidic platform via bioaerosol generation, and a liquid-type particle collection setup was used. We demonstrate successful discrimination of SYTO82-dyed fluorescent bacterial cells from other residue particles in a continuous and real-time manner. In comparison with traditional microscopy cell counting and colony culture methods, this micro-optofluidic platform is not only more accurate in terms of the detection efficiency for airborne microorganisms but it also provides additional information on the total particle number concentration.",2015 Nov 2,"['Choi, Jeongan', 'Kang, Miran', 'Jung, Jae Hee']",Sci Rep,,,True
243532558bf1aeed5200836620159cf37f91ab26,PMC,Non-periodic outbreaks of recurrent epidemics and its network modelling,http://dx.doi.org/10.1038/srep16010,PMC4629194,26521709,CC BY,"The study of recurrent epidemic outbreaks has been attracting great attention for decades, but its underlying mechanism is still under debate. Based on a large number of real data from different cities, we find that besides the seasonal periodic outbreaks of influenza, there are also non-periodic outbreaks, i.e. non-seasonal or non-annual behaviors. To understand how the non-periodicity shows up, we present a network model of SIRS epidemic with both time-dependent infection rate and a small possibility of persistent epidemic seeds, representing the influences from the larger annual variation of environment and the infection generated spontaneously in nature, respectively. Our numerical simulations reveal that the model can reproduce the non-periodic outbreaks of recurrent epidemics with the main features of real influenza data. Further, we find that the recurrent outbreaks of epidemic depend not only on the infection rate but also on the density of susceptible agents, indicating that they are both the necessary conditions for the recurrent epidemic patterns with non-periodicity. A theoretical analysis based on Markov dynamics is presented to explain the numerical results. This finding may be of significance to the control of recurrent epidemics.",2015 Nov 2,"['Zheng, Muhua', 'Wang, Chaoqing', 'Zhou, Jie', 'Zhao, Ming', 'Guan, Shuguang', 'Zou, Yong', 'Liu, Zonghua']",Sci Rep,,,True
793d754d6bda1aa545a47999e36e195b64839812,PMC,Non-periodic outbreaks of recurrent epidemics and its network modelling,http://dx.doi.org/10.1038/srep16010,PMC4629194,26521709,CC BY,"The study of recurrent epidemic outbreaks has been attracting great attention for decades, but its underlying mechanism is still under debate. Based on a large number of real data from different cities, we find that besides the seasonal periodic outbreaks of influenza, there are also non-periodic outbreaks, i.e. non-seasonal or non-annual behaviors. To understand how the non-periodicity shows up, we present a network model of SIRS epidemic with both time-dependent infection rate and a small possibility of persistent epidemic seeds, representing the influences from the larger annual variation of environment and the infection generated spontaneously in nature, respectively. Our numerical simulations reveal that the model can reproduce the non-periodic outbreaks of recurrent epidemics with the main features of real influenza data. Further, we find that the recurrent outbreaks of epidemic depend not only on the infection rate but also on the density of susceptible agents, indicating that they are both the necessary conditions for the recurrent epidemic patterns with non-periodicity. A theoretical analysis based on Markov dynamics is presented to explain the numerical results. This finding may be of significance to the control of recurrent epidemics.",2015 Nov 2,"['Zheng, Muhua', 'Wang, Chaoqing', 'Zhou, Jie', 'Zhao, Ming', 'Guan, Shuguang', 'Zou, Yong', 'Liu, Zonghua']",Sci Rep,,,False
055df119df20e08c2830c0b300173e343a760d38,PMC,"Ebola virus disease in the Democratic Republic of the Congo, 1976-2014",http://dx.doi.org/10.7554/eLife.09015,PMC4629279,26525597,CC BY,"The Democratic Republic of the Congo has experienced the most outbreaks of Ebola virus disease since the virus' discovery in 1976. This article provides for the first time a description and a line list for all outbreaks in this country, comprising 996 cases. Compared to patients over 15 years old, the odds of dying were significantly lower in patients aged 5 to 15 and higher in children under five (with 100% mortality in those under 2 years old). The odds of dying increased by 11% per day that a patient was not hospitalised. Outbreaks with an initially high reproduction number, R (>3), were rapidly brought under control, whilst outbreaks with a lower initial R caused longer and generally larger outbreaks. These findings can inform the choice of target age groups for interventions and highlight the importance of both reducing the delay between symptom onset and hospitalisation and rapid national and international response. DOI: http://dx.doi.org/10.7554/eLife.09015.001",,"['Rosello, Alicia', 'Mossoko, Mathias', 'Flasche, Stefan', 'Van Hoek, Albert Jan', 'Mbala, Placide', 'Camacho, Anton', 'Funk, Sebastian', 'Kucharski, Adam', 'Ilunga, Benoit Kebela', 'Edmunds, W John', 'Piot, Peter', 'Baguelin, Marc', 'Muyembe Tamfum, Jean-Jacques']",eLife.; 4:e09015,,,True
4a7c2c60763755a14783f728e9b4cde8bf899f09,PMC,"The role of host genetic factors in respiratory tract infectious diseases: systematic review, meta-analyses and field synopsis",http://dx.doi.org/10.1038/srep16119,PMC4630784,26524966,CC BY,"Host genetic factors have frequently been implicated in respiratory infectious diseases, often with inconsistent results in replication studies. We identified 386 studies from the total of 24,823 studies identified in a systematic search of four bibliographic databases. We performed meta-analyses of studies on tuberculosis, influenza, respiratory syncytial virus, SARS-Coronavirus and pneumonia. One single-nucleotide polymorphism from IL4 gene was significant for pooled respiratory infections (rs2070874; 1.66 [1.29–2.14]). We also detected an association of TLR2 gene with tuberculosis (rs5743708; 3.19 [2.03–5.02]). Subset analyses identified CCL2 as an additional risk factor for tuberculosis (rs1024611; OR = 0.79 [0.72–0.88]). The IL4-TLR2-CCL2 axis could be a highly interesting target for translation towards clinical use. However, this conclusion is based on low credibility of evidence - almost 95% of all identified studies had strong risk of bias or confounding. Future studies must build upon larger-scale collaborations, but also strictly adhere to the highest evidence-based principles in study design, in order to reduce research waste and provide clinically translatable evidence.",2015 Nov 3,"['Patarčić, Inga', 'Gelemanović, Andrea', 'Kirin, Mirna', 'Kolčić, Ivana', 'Theodoratou, Evropi', 'Baillie, Kenneth J.', 'de Jong, Menno D.', 'Rudan, Igor', 'Campbell, Harry', 'Polašek, Ozren']",Sci Rep,,,True
643ce1300f0c4056a709e1b13269a51924960a3a,PMC,Combination effects of ribavirin and interferons on severe fever with thrombocytopenia syndrome virus infection,http://dx.doi.org/10.1186/s12985-015-0412-3,PMC4630909,26527529,CC BY,"BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by SFTS virus and characterized by a high case fatality rate. Currently, there is no effective therapy for the disease. While the administration of ribavirin does not improve the case fatality rate or viral load in patient blood, it can inhibit viral infection in vitro. METHODS: Vero cells were pre-treated with interferons (IFNs) α, β, and γ alone and in combination with ribavirin drugs and inoculated with SFTS virus. Three days later, supernatants were harvested and subjected to virus titration. An unpaired t-test was used for statistical analysis of the drugs’ effects. RESULTS: While the effects of IFNγ at high concentrations were slightly weaker than those of the other IFNs, all IFNs showed dose-dependent inhibitory effects. The combined usage of IFNs with ribavirin at 90 % effective concentrations showed large inhibitory effects, with over a 3 log(10) reduction in viral titers. CONCLUSIONS: The combined usage of one of type-I/II IFNs with ribavirin drastically reduced SFTS virus infection and therefore may be useful in the treatment of SFTS.",2015 Nov 2,"['Shimojima, Masayuki', 'Fukushi, Shuetsu', 'Tani, Hideki', 'Taniguchi, Satoshi', 'Fukuma, Aiko', 'Saijo, Masayuki']",Virol J,,,True
27373ff091fe4a81ee4d6bfc09ece3995080c2ea,PMC,"Proteomic analysis of Pteropus alecto kidney cells in response to the viral mimic, Poly I:C",http://dx.doi.org/10.1186/s12953-015-0081-6,PMC4630911,26535029,CC BY,"BACKGROUND: Bats are recognised as an important reservoir for a number of highly pathogenic zoonotic viruses. While many of these viruses cause severe and often fatal disease in humans, bats are able to coexist with these viruses without clinical signs of disease. The mechanism conferring this antiviral response is not fully understood. Here, we investigated the differential protein expression of immortalised Pteropus alecto kidney cells (PaKiT03) following transfection with the viral mimic, Poly I:C. Two complementary proteomic approaches, difference gel electrophoresis (DIGE) and isobaric tagging for relative and absolute quantitation (iTRAQ) were used to quantify changes in protein expression following Poly I:C stimulation at 4, 8 and 20 hr post treatment (hpt). RESULTS: The expression of ISG54 gene, a known responder to virus infection and Poly I:C treatment, was significantly induced in transfected cells compared with mock-transfected cells. Through iTRAQ analysis we show that Poly I:C up-regulates key glycolytic enzymes at 4 hpt within PaKiT03 cells. In contrast, at 20 hpt PaKiT03 cells down-regulated ribosomal subunit proteins. The analysis with DIGE of Poly I:C transfected PaKiT03 cells showed over 215 individual spots differentially regulated, however only 25 spots could be unambiguously identified by LC-MS/MS. Immunoblotting confirmed the up-regulation of Eno1 and Tpi1 in PaKiT03 cells following Poly I:C transfection. A comparison with human cells (HEK293T and HeLa) and one additional bat cell line (PaLuT02), demonstrated that glycolytic pathways are also induced in these cell types, but at different intensities. CONCLUSION: The two techniques, DIGE and iTRAQ identified largely overlapping sets of differentially expressed proteins, however DIGE unambiguously identified significantly less proteins than iTRAQ. Poly I:C induced a rapid metabolic shift towards glycolysis within the PaKiT03 cells at 4 hpt, presumably as a consequence of increased energy requirements. On the other hand ribosomal subunit proteins were seen as down-regulated by iTRAQ, these proteins may be the limiting factors in the translational machinery available for virus replication. This study provides new insight into the antiviral response of bat cells, highlighting the importance of energy metabolism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12953-015-0081-6) contains supplementary material, which is available to authorized users.",2015 Nov 2,"['Mok, Lawrence', 'Wynne, James W.', 'Ford, Kris', 'Shiell, Brian', 'Bacic, Antony', 'Michalski, Wojtek P.']",Proteome Sci,,,True
0c433c7c4e2e090b2d89d8456f9febed54b71966,PMC,Bat and pig IFN-induced transmembrane protein 3 restrict cell entry by influenza virus and lyssaviruses,http://dx.doi.org/10.1099/vir.0.000058,PMC4631062,25614588,CC BY,"IFN-induced transmembrane protein 3 (IFITM3) is a restriction factor that blocks cytosolic entry of numerous viruses that utilize acidic endosomal entry pathways. In humans and mice, IFITM3 limits influenza-induced morbidity and mortality. Although many IFITM3-sensitive viruses are zoonotic, whether IFITMs function as antiviral restriction factors in mammalian species other than humans and mice is unknown. Here, IFITM3 orthologues in the microbat (Myotis myotis) and pig (Sus scrofa domesticus) were identified using rapid amplification of cDNA ends. Amino acid residues known to be important for IFITM3 function were conserved in the pig and microbat orthologues. Ectopically expressed pig and microbat IFITM3 co-localized with transferrin (early endosomes) and CD63 (late endosomes/multivesicular bodies). Pig and microbat IFITM3 restricted cell entry mediated by multiple influenza haemagglutinin subtypes and lyssavirus glycoproteins. Expression of pig or microbat IFITM3 in A549 cells reduced influenza virus yields and nucleoprotein expression. Conversely, small interfering RNA knockdown of IFITM3 in pig NPTr cells and primary microbat cells enhanced virus replication, demonstrating that these genes are functional in their species of origin at endogenous levels. In summary, we showed that IFITMs function as potent broad-spectrum antiviral effectors in two mammals – pigs and bats – identified as major reservoirs for emerging viruses.",2015 May,"['Benfield, Camilla T. O.', 'Smith, Sarah E.', 'Wright, Edward', 'Wash, Rachael S.', 'Ferrara, Francesca', 'Temperton, Nigel J.', 'Kellam, Paul']",J Gen Virol,,,True
51a7b35db673f0d7cb14a80b607192e3f44cc7f5,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,True
92b94c1462d7b041b4384427330fb96356a460d3,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
6d2d02b0a6ecb9c3b18b5493a915c98aef617c4c,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
dbc083ba64144327640e834733ed3bdd22547ac1,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
efe3c8971043fad4fc42ab12968b8c281ab51993,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
94aa6c926b7d24d310c5e1f69e855a4cf2629a47,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
2c5f2f209d53eb9970b4e4af47eb142bcb439af1,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
7ba894b5e65044ba373e4a09430c3dc4c069bbab,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
d4dd5cbb2f849bfaf7aeff57858e8cf5429d4698,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
d053a0f318f0d42cf1c06dabf67e94e944ec7da4,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
48daab48d460ec33f5f8263bd5ac7aa866490e48,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
239ca8536007960c7aed8369da414b93702217f2,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
ed468ccf95499f1d19c071accb82a8bc64696ace,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,True
55b2f19377928da52d9826a5de0714e5c75ebd02,PMC,The Effects of Media Reports on Disease Spread and Important Public Health Measurements,http://dx.doi.org/10.1371/journal.pone.0141423,PMC4631512,26528909,CC BY,"Controlling the spread of influenza to reduce the effects of infection on a population is an important mandate of public health. Mass media reports on an epidemic or pandemic can provide important information to the public, and in turn, can induce positive healthy behaviour practices (i.e., handwashing, social distancing) in the individuals, that will reduce the probability of contracting the disease. Mass media fatigue, however, can dampen these effects. Mathematical models can be used to study the effects of mass media reports on epidemic/pandemic outcomes. In this study we employ a stochastic agent based model to provide a quantification of mass media reports on the variability in important public health measurements. We also include mass media report data compiled by the Global Public Health Intelligence Network, to study the effects of mass media reports in the 2009 H1N1 pandemic. We find that the report rate and the rate at which individuals relax their healthy behaviours (media fatigue) greatly affect the variability in important public health measurements. When the mass media reporting data is included in the model, two peaks of infection result.",2015 Nov 3,"['Collinson, Shannon', 'Khan, Kamran', 'Heffernan, Jane M.']",PLoS One,,,True
c9b76a5f0e49ab1510fa1161baf7d588656582f6,PMC,Viroporins: Structures and Functions beyond Cell Membrane Permeabilization,http://dx.doi.org/10.3390/v7102866,PMC4632374,26702461,CC BY,,2015 Sep 29,"['Nieva, José Luis', 'Carrasco, Luis']",Viruses,,,True
75e5e406f83b2f0a94abc8cbed71cbb900f9956e,PMC,The Role of Electron Microscopy in Studying the Continuum of Changes in Membranous Structures during Poliovirus Infection,http://dx.doi.org/10.3390/v7102874,PMC4632382,26473912,CC BY,"Replication of the poliovirus genome is localized to cytoplasmic replication factories that are fashioned out of a mixture of viral proteins, scavenged cellular components, and new components that are synthesized within the cell due to viral manipulation/up-regulation of protein and phospholipid synthesis. These membranous replication factories are quite complex, and include markers from multiple cytoplasmic cellular organelles. This review focuses on the role of electron microscopy in advancing our understanding of poliovirus RNA replication factories. Structural data from the literature provide the basis for interpreting a wide range of biochemical studies that have been published on virus-induced lipid biosynthesis. In combination, structural and biochemical experiments elucidate the dramatic membrane remodeling that is a hallmark of poliovirus infection. Temporal and spatial membrane modifications throughout the infection cycle are discussed. Early electron microscopy studies of morphological changes following viral infection are re-considered in light of more recent data on viral manipulation of lipid and protein biosynthesis. These data suggest the existence of distinct subcellular vesicle populations, each of which serves specialized roles in poliovirus replication processes.",2015 Oct 12,"['Rossignol, Evan D.', 'Yang, Jie E.', 'Bullitt, Esther']",Viruses,,,True
a599eb2c6ca51522fa234d8059f989569f4fe298,PMC,Emerging Roles of Viroporins Encoded by DNA Viruses: Novel Targets for Antivirals?,http://dx.doi.org/10.3390/v7102880,PMC4632388,26501313,CC BY,"Studies have highlighted the essential nature of a group of small, highly hydrophobic, membrane embedded, channel-forming proteins in the life cycles of a growing number of RNA viruses. These viroporins mediate the flow of ions and a range of solutes across cellular membranes and are necessary for manipulating a myriad of host processes. As such they contribute to all stages of the virus life cycle. Recent discoveries have identified proteins encoded by the small DNA tumor viruses that display a number of viroporin like properties. This review article summarizes the recent developments in our understanding of these novel viroporins; describes their roles in the virus life cycles and in pathogenesis and speculates on their potential as targets for anti-viral therapeutic intervention.",2015 Oct 16,"['Royle, Jamie', 'Dobson, Samuel John', 'Müller, Marietta', 'Macdonald, Andrew']",Viruses,,,True
f6a6f1fcc991eaf6e733d88adb25a3a7a8e65546,PMC,Sequence and Structure Analysis of Distantly-Related Viruses Reveals Extensive Gene Transfer between Viruses and Hosts and among Viruses,http://dx.doi.org/10.3390/v7102882,PMC4632390,26492264,CC BY,"The origin and evolution of viruses is a subject of ongoing debate. In this study, we provide a full account of the evolutionary relationships between proteins of significant sequence and structural similarity found in viruses that belong to different classes according to the Baltimore classification. We show that such proteins can be found in viruses from all Baltimore classes. For protein families that include these proteins, we observe two patterns of the taxonomic spread. In the first pattern, they can be found in a large number of viruses from all implicated Baltimore classes. In the other pattern, the instances of the corresponding protein in species from each Baltimore class are restricted to a few compact clades. Proteins with the first pattern of distribution are products of so-called viral hallmark genes reported previously. Additionally, this pattern is displayed by the envelope glycoproteins from Flaviviridae and Bunyaviridae and helicases of superfamilies 1 and 2 that have homologs in cellular organisms. The second pattern can often be explained by horizontal gene transfer from the host or between viruses, an example being Orthomyxoviridae and Coronaviridae hemagglutinin esterases. Another facet of horizontal gene transfer comprises multiple independent introduction events of genes from cellular organisms into otherwise unrelated viruses.",2015 Oct 19,"['Caprari, Silvia', 'Metzler, Saskia', 'Lengauer, Thomas', 'Kalinina, Olga V.']",Viruses,,,True
8f44e4d806117b957383a7ee870d2dd38213f094,PMC,Perspective of Use of Antiviral Peptides against Influenza Virus,http://dx.doi.org/10.3390/v7102883,PMC4632391,26492266,CC BY,"The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20(th) century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides.",2015 Oct 20,"['Skalickova, Sylvie', 'Heger, Zbynek', 'Krejcova, Ludmila', 'Pekarik, Vladimir', 'Bastl, Karel', 'Janda, Jozef', 'Kostolansky, Frantisek', 'Vareckova, Eva', 'Zitka, Ondrej', 'Adam, Vojtech', 'Kizek, Rene']",Viruses,,,True
578ad49441884c636eb9d6044237708eb6437afb,PMC,Complete Genome and Phylogeny of Puumala Hantavirus Isolates Circulating in France,http://dx.doi.org/10.3390/v7102884,PMC4632392,26506370,CC BY,"Puumala virus (PUUV) is the agent of nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) in Europe. NE incidence presents a high spatial variation throughout France, while the geographical distribution of the wild reservoir of PUUV, the bank vole, is rather continuous. A missing piece of the puzzle is the current distribution and the genetic variation of PUUV in France, which has been overlooked until now and remains poorly understood. During a population survey, from 2008 to 2011, bank voles were trapped in eight different forests of France located in areas known to be endemic for NE or in area from where no NE case has been reported until now. Bank voles were tested for immunoglobulin (Ig)G ELISA serology and two seropositive animals for each of three different areas (Ardennes, Jura and Orleans) were then subjected to laboratory analyses in order to sequence the whole S, M and L segments of PUUV. Phylogenetic analyses revealed that French PUUV isolates globally belong to the central European (CE) lineage although isolates from Ardennes are clearly distinct from those in Jura and Orleans, suggesting a different evolutionary history and origin of PUUV introduction in France. Sequence analyses revealed specific amino acid signatures along the N protein, including in PUUV from the Orleans region from where NE in humans has never been reported. The relevance of these mutations in term of pathophysiology is discussed.",2015 Oct 22,"['Castel, Guillaume', 'Couteaudier, Mathilde', 'Sauvage, Frank', 'Pons, Jean-Baptiste', 'Murri, Séverine', 'Plyusnina, Angelina', 'Pontier, Dominique', 'Cosson, Jean-François', 'Plyusnin, Alexander', 'Marianneau, Philippe', 'Tordo, Noël']",Viruses,,,True
3e3097dd0c6d06cce3de6c065c6558807d12ae7e,PMC,Complete Genome and Phylogeny of Puumala Hantavirus Isolates Circulating in France,http://dx.doi.org/10.3390/v7102884,PMC4632392,26506370,CC BY,"Puumala virus (PUUV) is the agent of nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) in Europe. NE incidence presents a high spatial variation throughout France, while the geographical distribution of the wild reservoir of PUUV, the bank vole, is rather continuous. A missing piece of the puzzle is the current distribution and the genetic variation of PUUV in France, which has been overlooked until now and remains poorly understood. During a population survey, from 2008 to 2011, bank voles were trapped in eight different forests of France located in areas known to be endemic for NE or in area from where no NE case has been reported until now. Bank voles were tested for immunoglobulin (Ig)G ELISA serology and two seropositive animals for each of three different areas (Ardennes, Jura and Orleans) were then subjected to laboratory analyses in order to sequence the whole S, M and L segments of PUUV. Phylogenetic analyses revealed that French PUUV isolates globally belong to the central European (CE) lineage although isolates from Ardennes are clearly distinct from those in Jura and Orleans, suggesting a different evolutionary history and origin of PUUV introduction in France. Sequence analyses revealed specific amino acid signatures along the N protein, including in PUUV from the Orleans region from where NE in humans has never been reported. The relevance of these mutations in term of pathophysiology is discussed.",2015 Oct 22,"['Castel, Guillaume', 'Couteaudier, Mathilde', 'Sauvage, Frank', 'Pons, Jean-Baptiste', 'Murri, Séverine', 'Plyusnina, Angelina', 'Pontier, Dominique', 'Cosson, Jean-François', 'Plyusnin, Alexander', 'Marianneau, Philippe', 'Tordo, Noël']",Viruses,,,False
bfe634ff1fa0e8f0a43c1bd5fa6e0b5bd17705ee,PMC,Comparative Genomic Analysis of Classical and Variant Virulent Parental/Attenuated Strains of Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.3390/v7102891,PMC4632399,26512689,CC BY,"Since 2010, the variant porcine epidemic diarrhea virus (PEDV) has been the etiological agent responsible for the outbreak of porcine epidemic diarrhea (PED) worldwide. In this study, a variant PEDV strain YN1 was isolated, serially propagated on the Vero cells and was characterized for 200 passages. To better elucidate the molecular basis of Vero cell adaptation of variant PEDV strains, we sequenced, compared, and analyzed the full-genome sequences of parental YN1 and passages 15, 30, 60, 90, 144, and 200. The results showed that the variations increased with the viral passage. The nucleotides sequences of non-structural protein (NSP)2, NSP4-7, NSP10, NSP12 and NSP13 genes did not change during the Vero cell adaptation process. After comparison of the variation characteristic of classical, variant virulent/attenuated strains, it was found that attenuation of PEDV virus was associated with 9−26 amino acid (aa) changes in open reading frames (ORF) 1a/b and S protein, early termination in ORF3, 1–3 aa changes in E, M and N protein and some nucleotide sequences’ synonymous mutations. The aa deletion at about 144 aa of S protein could be the attenuation marker for the PEDV. The pig study showed that the early termination in ORF3 was more important for virus cell adaptation than virus attenuation.",2015 Oct 23,"['Chen, Fangzhou', 'Zhu, Yinxing', 'Wu, Meizhou', 'Ku, Xugang', 'Ye, Shiyi', 'Li, Zhonghua', 'Guo, Xiaozhen', 'He, Qigai']",Viruses,,,True
060833389f07819960d34c91e0dfdc92e053f6ac,PMC,Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2,http://dx.doi.org/10.3390/v7102893,PMC4632401,26512690,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) infection strongly modulates the host’s immune response. The RNA silencing pathway is an intracellular innate response to viral infections. However, it is unknown whether PRRSV interacts with cellular RNA silencing to facilitate the viral infection. Here, we report for the first time the interaction between PRRSV and RNA silencing in both the porcine macrophages and African green monkey kidney cell line (MARC-145) cell line, which were derived from African green monkey kidney cells and highly permissive for PRRSV infection. Our data demonstrated that PRRSV suppressed RNA silencing induced by short-hairpin (sh) RNA, double-strand (ds) RNA and microRNA (miRNA) and downregulated the expression of argonaute protein-2 (Ago-2), which is a key protein of the RNA silencing pathway in animal cells. Further, exogenous introduction of siRNA and shRNA downregulated Dicer or Ago-2 proteins of the cellular RNA silencing apparatus in MARC-145 cells and porcine macrophages, which, in turn, increased the viral replication and titers. The viral non-structure protein 1α (nsp-1α) and nsp11 of PRRSV were identified as the suppressors for cellular RNA silencing (RSSs) to downregulate the Ago-2 protein. Our results identify that PRRSV, through its nsp proteins, suppresses the cellular RNA silencing apparatus in favor of viral infection and supports a co-evolutionary process of the virus and the cellular RNA silencing process.",2015 Oct 23,"['Chen, Jing', 'Shi, Xibao', 'Zhang, Xiaozhuan', 'Wang, Li', 'Luo, Jun', 'Xing, Guangxu', 'Deng, Ruiguang', 'Yang, Hong', 'Li, Jinting', 'Wang, Aiping', 'Zhang, Gaiping']",Viruses,,,True
57599ec2644e90c8c79737ed565edb7d6b286fc5,PMC,Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase,http://dx.doi.org/10.3390/v7102894,PMC4632402,26516899,CC BY,"The Sabin I poliovirus live, attenuated vaccine strain encodes for four amino acid changes (i.e., D53N, Y73H, K250E, and T362I) in the RNA-dependent RNA polymerase (RdRp). We have previously shown that the T362I substitution leads to a lower fidelity RdRp, and viruses encoding this variant are attenuated in a mouse model of poliovirus. Given these results, it was surprising that the nucleotide incorporation rate and nucleobase fidelity of the Sabin I RdRp is similar to that of wild-type enzyme, although the Sabin I RdRp is less selective against nucleotides with modified sugar groups. We suggest that the other Sabin amino acid changes (i.e., D53N, Y73H, K250E) help to re-establish nucleotide incorporation rates and nucleotide discrimination near wild-type levels, which may be a requirement for the propagation of the virus and its efficacy as a vaccine strain. These results also suggest that the nucleobase fidelity of the Sabin I RdRp likely does not contribute to viral attenuation.",2015 Oct 26,"['Liu, Xinran', 'Musser, Derek M.', 'Lee, Cheri A.', 'Yang, Xiaorong', 'Arnold, Jamie J.', 'Cameron, Craig E.', 'Boehr, David D.']",Viruses,,,True
0706374e8a8a5eaf3bff4d2555c0f0db11294755,PMC,The Ethanol Extract from Lonicera japonica Thunb. Regresses Nonalcoholic Steatohepatitis in a Methionine- and Choline-Deficient Diet-Fed Animal Model,http://dx.doi.org/10.3390/nu7105423,PMC4632443,26506376,CC BY,"Nonalcoholic steatohepatitis (NASH) is characterized as fat accumulation in the hepatic tissue associated with various degrees of inflammation and progressive fibrosis. The potent anti-inflammatory and ethnopharmacological properties of Lonicera japonica Thunb. (Caprifoliaceae) make it an excellent source of novel medicinal targets for the treatment of NASH. The aim of the study was to investigate the effects of L. japonica ethanol extract (LJEE) on NASH in mice. C57BL/6J mice were fed with methionine-choline-deficient diet (MCDD) for eight weeks to promote the development of NASH. After development of the model, the mice were administered LJEE once daily via oral gavage at doses of 100, 200, or 300 mg/kg for another four weeks. Simultaneous treatments with LJEE (300 mg/kg/day) resulted in pronounced improvements in liver steatosis, ballooning degeneration, and inflammation. LJEE prevented MCDD-induced plasma level increases in aspartate aminotransferase and alanine aminotransferase. LJEE significantly reduced hepatic malondialdehyde level and ameliorated hepatic inflammation and fibrosis in MCDD-fed mice, which were associated with down-regulation of cytochrome P450 2E1 suppression of multiple proinflammatory and profibrotic genes. LJEE can prevent hepatic steatosis by reducing hepatic peroxisome acyl-CoA:diacylglycerol acyltransferase 2 expression, as well as by inducing proliferator-activated receptor α expression. In addition, the LJEE treatments caused significant reduction in the phosphorylated form of Jun N-terminal kinase along with an increase in the phosphorylated level of extra cellular signal-regulated kinase 1/2. Our study demonstrated the protective role of LJEE in ameliorating nutritional steatohepatitis.",2015 Oct 21,"['Tzeng, Thing-Fong', 'Tzeng, Yu-Cheng', 'Cheng, Yu-Jou', 'Liou, Shorong-Shii', 'Liu, I-Min']",Nutrients,,,True
71f45bcdac8e83e02ee1d8b5eab8ce5c425f5cce,PMC,Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins,http://dx.doi.org/10.3390/molecules20034610,PMC4633014,25774492,CC BY,"Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA), for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV), and human cytomegalovirus (HCMV). In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man(9)GlcNAc(2)Asn (Man9)-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn). These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation.",2015 Mar 12,"['Wang, Denong', 'Tang, Jin', 'Tang, Jiulai', 'Wang, Lai-Xi']",Molecules,,,True
07330c35eb8beda0a4b515b8a0edce5d42662417,PMC,Detection of a novel astrovirus from a black-naped monarch (Hypothymis azurea) in Cambodia,http://dx.doi.org/10.1186/s12985-015-0413-2,PMC4634723,26537007,CC BY,"BACKGROUND: Astroviruses are comprised of two genera with Avastrovirus infecting birds and Mamastrovirus infecting mammals. Avastroviruses have primarily been associated with infections of poultry, especially chicken, turkey, duck, and guineafowl production systems, but also infect wading birds and doves. Outcomes result in a spectrum of disease, ranging from asymptomatic shedding to gastroenteritis with diarrhea, stunting, failure to thrive and death. FINDINGS: Virological surveillance was conducted in birds from two sites in Cambodia in 2010. Samples were screened for influenza, astroviruses, coronaviruses, flaviviruses, and paramyxoviruses. A total of 199 birds were tested and an astrovirus was detected in a black-naped monarch (Hypothymis azurea). CONCLUSIONS: This is the first astrovirus detection in a passerine bird. Phylogenetic analysis and nucleotide distances suggest that this avastrovirus forms a distinct lineage and may constitute a fourth avastrovirus group. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0413-2) contains supplementary material, which is available to authorized users.",2015 Nov 4,"['Mendenhall, Ian H.', 'Yaung, Katherine Nay', 'Joyner, Priscilla H.', 'Keatts, Lucy', 'Borthwick, Sophie', 'Neves, Erica Sena', 'San, Sorn', 'Gilbert, Martin', 'Smith, Gavin JD']",Virol J,,,True
8e7d05c2e304aa0430befd8259b9bb6c863a0f29,PMC,Detection of a novel astrovirus from a black-naped monarch (Hypothymis azurea) in Cambodia,http://dx.doi.org/10.1186/s12985-015-0413-2,PMC4634723,26537007,CC BY,"BACKGROUND: Astroviruses are comprised of two genera with Avastrovirus infecting birds and Mamastrovirus infecting mammals. Avastroviruses have primarily been associated with infections of poultry, especially chicken, turkey, duck, and guineafowl production systems, but also infect wading birds and doves. Outcomes result in a spectrum of disease, ranging from asymptomatic shedding to gastroenteritis with diarrhea, stunting, failure to thrive and death. FINDINGS: Virological surveillance was conducted in birds from two sites in Cambodia in 2010. Samples were screened for influenza, astroviruses, coronaviruses, flaviviruses, and paramyxoviruses. A total of 199 birds were tested and an astrovirus was detected in a black-naped monarch (Hypothymis azurea). CONCLUSIONS: This is the first astrovirus detection in a passerine bird. Phylogenetic analysis and nucleotide distances suggest that this avastrovirus forms a distinct lineage and may constitute a fourth avastrovirus group. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0413-2) contains supplementary material, which is available to authorized users.",2015 Nov 4,"['Mendenhall, Ian H.', 'Yaung, Katherine Nay', 'Joyner, Priscilla H.', 'Keatts, Lucy', 'Borthwick, Sophie', 'Neves, Erica Sena', 'San, Sorn', 'Gilbert, Martin', 'Smith, Gavin JD']",Virol J,,,True
136f5dd69cd65fb0826ded4d9f51af7969dfcbcd,PMC,Suppression subtractive hybridization method for the identification of a new strain of murine hepatitis virus from xenografted SCID mice,http://dx.doi.org/10.1007/s00705-015-2592-y,PMC4635179,26347284,CC BY,"During attempts to clone retroviral determinants associated with a mouse model of Langerhans cell histiocytosis (LCH), suppression subtractive hybridization (SSH) was used to identify unique viruses in the liver of severe combined immunodeficiency (SCID) mice transplanted with LCH tissues. A partial genomic sequence of a murine coronavirus was identified, and the whole genome (31428 bp) of the coronavirus was subsequently sequenced using PCR cloning techniques. Nucleotide sequence comparisons revealed that the genome sequence of the new virus was 91-93 % identical to those of known murine hepatitis viruses (MHVs). The predicted open reading frame from the nucleotide sequence encoded all known proteins of MHVs. Analysis at the protein level showed that the virus was closely related to the highly virulent MHV-JHM strain. The virus strain was named MHV-MI. No type D retroviruses were found. Degenerate PCR targeting of type D retrovirus and 5′-RACE targeting of other types of retroviruses confirmed the absence of any retroviral association with the LCH xenografted SCID mice.",2015 Sep 8,"['Islam, Mohammed M.', 'Toohey, Brendan', 'Purcell, Damian F. J.', 'Kannourakis, George']",Arch Virol,,,True
d85ef5950a1be68a4dd4eebed557563bf88ba8ff,PMC,Genotyping coronaviruses associated with feline infectious peritonitis,http://dx.doi.org/10.1099/vir.0.000084,PMC4635486,25667330,CC BY,"Feline coronavirus (FCoV) infections are endemic among cats worldwide. The majority of infections are asymptomatic or result in only mild enteric disease. However, approximately 5 % of cases develop feline infectious peritonitis (FIP), a systemic disease that is a frequent cause of death in young cats. In this study, we report the complete coding genome sequences of six FCoVs: three from faecal samples from healthy cats and three from tissue lesion samples from cats with confirmed FIP. The six samples were obtained over a period of 8 weeks at a single-site cat rescue and rehoming centre in the UK. We found amino acid differences located at 44 positions across an alignment of the six virus translatomes and, at 21 of these positions, the differences fully or partially discriminated between the genomes derived from the faecal samples and the genomes derived from the tissue lesion samples. In this study, two amino acid differences fully discriminated the two classes of genomes: these were both located in the S2 domain of the virus surface glycoprotein gene. We also identified deletions in the 3c protein ORF of genomes from two of the FIP samples. Our results support previous studies that implicate S protein mutations in the pathogenesis of FIP.",2015 Jun,"['Lewis, Catherine S.', 'Porter, Emily', 'Matthews, David', 'Kipar, Anja', 'Tasker, Séverine', 'Helps, Christopher R.', 'Siddell, Stuart G.']",J Gen Virol,,,True
b9795ebc63bc667ed27545d63f287cacf8604d62,PMC,Discovery of a polyomavirus in European badgers (Meles meles) and the evolution of host range in the family Polyomaviridae,http://dx.doi.org/10.1099/vir.0.000071,PMC4635489,25626684,CC BY,"Polyomaviruses infect a diverse range of mammalian and avian hosts, and are associated with a variety of symptoms. However, it is unknown whether the viruses are found in all mammalian families and the evolutionary history of the polyomaviruses is still unclear. Here, we report the discovery of a novel polyomavirus in the European badger (Meles meles), which to our knowledge represents the first polyomavirus to be characterized in the family Mustelidae, and within a European carnivoran. Although the virus was discovered serendipitously in the supernatant of a cell culture inoculated with badger material, we subsequently confirmed its presence in wild badgers. The European badger polyomavirus was tentatively named Meles meles polyomavirus 1 (MmelPyV1). The genome is 5187 bp long and encodes proteins typical of polyomaviruses. Phylogenetic analyses including all known polyomavirus genomes consistently group MmelPyV1 with California sea lion polyomavirus 1 across all regions of the genome. Further evolutionary analyses revealed phylogenetic discordance amongst polyomavirus genome regions, possibly arising from evolutionary rate heterogeneity, and a complex association between polyomavirus phylogeny and host taxonomic groups.",2015 Jun,"['Hill, Sarah C.', 'Murphy, Aisling A.', 'Cotten, Matthew', 'Palser, Anne L.', 'Benson, Phillip', 'Lesellier, Sandrine', 'Gormley, Eamonn', 'Richomme, Céline', 'Grierson, Sylvia', 'Bhuachalla, Deirdre Ni', 'Chambers, Mark', 'Kellam, Paul', 'Boschiroli, María-Laura', 'Ehlers, Bernhard', 'Jarvis, Michael A.', 'Pybus, Oliver G.']",J Gen Virol,,,True
ef6361c7bffb9e92f397d7004bfb3a9c804d7c6a,PMC,"Viral Respiratory Tract Infections in Adult Patients Attending Outpatient and Emergency Departments, Taiwan, 2012–2013: A PCR/Electrospray Ionization Mass Spectrometry Study",http://dx.doi.org/10.1097/MD.0000000000001545,PMC4635751,26402811,CC BY,"Viral etiologies of respiratory tract infections (RTIs) have been less studied in adult than in pediatric populations. Furthermore, the ability of PCR/electrospray ionization mass spectrometry (PCR/ESI-MS) to detect enteroviruses and rhinoviruses in respiratory samples has not been well evaluated. We sought to use PCR/ESI-MS to comprehensively investigate the viral epidemiology of adult RTIs, including testing for rhinoviruses and enteroviruses. Nasopharyngeal or throat swabs from 267 adults with acute RTIs (212 upper RTIs and 55 lower RTIs) who visited a local clinic or the outpatient or emergency departments of a medical center in Taiwan between October 2012 and June 2013 were tested for respiratory viruses by both virus isolation and PCR/ESI-MS. Throat swabs from 15 patients with bacterial infections and 27 individuals without active infections were included as control samples. Respiratory viruses were found in 23.6%, 47.2%, and 47.9% of the 267 cases by virus isolation, PCR/ESI-MS, and both methods, respectively. When both methods were used, the influenza A virus (24.3%) and rhinoviruses (9.4%) were the most frequently identified viruses, whereas human coronaviruses, human metapneumovirus (hMPV), enteroviruses, adenoviruses, respiratory syncytial virus, and parainfluenza viruses were identified in small proportions of cases (<5% of cases for each type of virus). Coinfection was observed in 4.1% of cases. In the control group, only 1 (2.4%) sample tested positive for a respiratory virus by PCR/ESI-MS. Patients who were undergoing steroid treatment, had an active malignancy, or suffered from chronic obstructive pulmonary disease (COPD) were at risk for rhinovirus, hMPV, or parainfluenza infections, respectively. Overall, immunocompromised patients, patients with COPD, and patients receiving dialysis were at risk for noninfluenza respiratory virus infection. Rhinoviruses (12.7%), influenza A virus (10.9%), and parainfluenza viruses (7.3%) were the most common viruses involved in the 55 cases of lower RTIs. The factors of parainfluenza infection, old age, and immunosuppression were independently associated with lower RTIs. In conclusion, PCR/ESI-MS improved the diagnostic yield for viral RTIs. Non-influenza respiratory virus infections were associated with patients with comorbidities and with lower RTIs. Additional studies that delineate the clinical need for including non-influenza respiratory viruses in the diagnostic work-up in these populations are warranted.",2015 Sep 25,"['Shih, Hsin-I', 'Wang, Hsuan-Chen', 'Su, Ih-Jen', 'Hsu, Hsiang-Chin', 'Wang, Jen-Ren', 'Sun, Hsiao Fang Sunny', 'Chou, Chien-Hsuan', 'Ko, Wen-Chien', 'Hsieh, Ming-I', 'Wu, Chi-Jung']",Medicine (Baltimore),,,True
dacc557b6e40bb69974e2e1a831aef665e524867,PMC,Cleavage of a Neuroinvasive Human Respiratory Virus Spike Glycoprotein by Proprotein Convertases Modulates Neurovirulence and Virus Spread within the Central Nervous System,http://dx.doi.org/10.1371/journal.ppat.1005261,PMC4636366,26545254,CC BY,"Human coronaviruses (HCoV) are respiratory pathogens that may be associated with the development of neurological diseases, in view of their neuroinvasive and neurotropic properties. The viral spike (S) glycoprotein is a major virulence factor for several coronavirus species, including the OC43 strain of HCoV (HCoV-OC43). In an attempt to study the role of this protein in virus spread within the central nervous system (CNS) and neurovirulence, as well as to identify amino acid residues important for such functions, we compared the sequence of the S gene found in the laboratory reference strain HCoV-OC43 ATCC VR-759 to S sequences of viruses detected in clinical isolates from the human respiratory tract. We identified one predominant mutation at amino acid 758 (from RRSR↓ G (758) to RRSR↓R (758)), which introduces a putative furin-like cleavage (↓) site. Using a molecular cDNA infectious clone to generate a corresponding recombinant virus, we show for the first time that such point mutation in the HCoV-OC43 S glycoprotein creates a functional cleavage site between the S1 and S2 portions of the S protein. While the corresponding recombinant virus retained its neuroinvasive properties, this mutation led to decreased neurovirulence while potentially modifying the mode of virus spread, likely leading to a limited dissemination within the CNS. Taken together, these results are consistent with the adaptation of HCoV-OC43 to the CNS environment, resulting from the selection of quasi-species harboring mutations that lead to amino acid changes in viral genes, like the S gene in HCoV-OC43, which may contribute to a more efficient establishment of a less pathogenic but persistent CNS infection. This adaptative mechanism could potentially be associated with human encephalitis or other neurological degenerative pathologies.",2015 Nov 6,"['Le Coupanec, Alain', 'Desforges, Marc', 'Meessen-Pinard, Mathieu', 'Dubé, Mathieu', 'Day, Robert', 'Seidah, Nabil G.', 'Talbot, Pierre J.']",PLoS Pathog,,,True
696ae2cd59982a2cb456ed723adb98586ebdf7f7,PMC,Ultrasensitive Detection of RNA and DNA Viruses Simultaneously Using Duplex UNDP-PCR Assay,http://dx.doi.org/10.1371/journal.pone.0141545,PMC4636378,26544710,CC BY,"Mixed infection of multiple viruses is common in modern intensive pig rearing. However, there are no methods available to detect DNA and RNA viruses in the same reaction system in preclinical level. In this study, we aimed to develop a duplex ultrasensitive nanoparticle DNA probe-based PCR assay (duplex UNDP-PCR) that was able to simultaneously detect DNA and RNA viruses in the same reaction system. PCV2 and TGEV are selected as representatives of the two different types of viruses. PCV2 DNA and TGEV RNA were simultaneously released from the serum sample by boiling with lysis buffer, then magnetic beads and gold nanoparticles coated with single and/or duplex specific probes for TGEV and PCV2 were added to form a sandwich-like complex with nucleic acids released from viruses. After magnetic separation, DNA barcodes specific for PCV2 and TGEV were eluted using DTT and characterized by specific PCR assay for specific DNA barcodes subsequently. The duplex UNDP-PCR showed similar sensitivity as that of single UNDP-PCR and was able to detect 20 copies each of PCV2 and TGEV in the serum, showing approximately 250-fold more sensitivity than conventional duplex PCR/RT-PCR assays. No cross-reaction was observed with other viruses. The positive detection rate of single MMPs- and duplex MMPs-based duplex UNDP-PCR was identical, with 29.6% for PCV2, 9.3% for TGEV and 3.7% for PCV2 and TGEV mixed infection. This duplex UNDP-PCR assay could detect TGEV (RNA virus) and PCV2 (DNA virus) from large-scale serum samples simultaneously without the need for DNA/RNA extraction, purification and reverse transcription of RNA, and showed a significantly increased positive detection rate for PCV2 (29%) and TGEV (11.7%) preclinical infection than conventional duplex PCR/RT-PCR. Therefore, the established duplex UNDP-PCR is a rapid and economical detection method, exhibiting high sensitivity, specificity and reproducibility.",2015 Nov 6,"['Huang, Yong', 'Xing, Na', 'Wang, Zengguo', 'Zhang, Xiujuan', 'Zhao, Xiaomin', 'Du, Qian', 'Chang, Lingling', 'Tong, Dewen']",PLoS One,,,True
543819a7a29de2c78dd6e147beed7be72466c610,PMC,Capacity building in national influenza laboratories – use of laboratory assessments to drive progress,http://dx.doi.org/10.1186/s12879-015-1232-1,PMC4636816,26546333,CC BY,"BACKGROUND: Laboratory testing is a fundamental component of influenza surveillance for detecting novel strains with pandemic potential and informing biannual vaccine strain selection. The United States (U.S.) Centers for Disease Control and Prevention (CDC), under the auspices of its WHO Collaborating Center for Influenza, is one of the major public health agencies which provides support globally to build national capacity for influenza surveillance. Our main objective was to determine if laboratory assessments supported capacity building efforts for improved global influenza surveillance. METHODS: In 2010, 35 national influenza laboratories were assessed in 34 countries, using a standardized tool. Post-assessment, each laboratory received a report with a list of recommendations for improvement. Uptake of recommendations were reviewed 3.2 mean years after the initial assessments and categorized as complete, in-progress, no action or no update. This was a retrospective study; follow-up took place through routine project management rather than at a set time-point post-assessment. WHO data on National Influenza Centre (NIC) designation, External Quality Assessment Project (EQAP) participation and FluNet reporting was used to measure laboratory capacity longitudinally and independently of the assessments. All data was further stratified by World Bank country income category. RESULTS: At follow-up, 81 % of 614 recommendations were either complete (350) or in-progress (145) for 32 laboratories (91 % response rate). The number of countries reporting to FluNet and the number of specimens they reported annually increased between 2005, when they were first funded by CDC, and 2010, the assessment year (p < 0.01). Improvements were also seen in EQAP participation and NIC designation over time and more so for low and lower-middle income countries. CONCLUSIONS: Assessments using a standardized tool have been beneficial to improving laboratory-based influenza surveillance. Specific recommendations helped countries identify and prioritize areas for improvement. Data from assessments helped CDC focus its technical assistance by country and region. Low and lower-middle income countries made greater improvements in their laboratories compared with upper-middle income countries. Future research could include an analysis of annual funding and technical assistance by country. Our approach serves as an example for capacity building for other diseases.",2015 Nov 6,"['Johnson, Lucinda E. A.', 'Muir-Paulik, Sarah A.', 'Kennedy, Pam', 'Lindstrom, Steven', 'Balish, Amanda', 'Aden, Tricia', 'Moen, Ann C.']",BMC Infect Dis,,,True
3d91360fc7a5df1058b9db9e8615ffef804edacf,PMC,Use of ward closure to control outbreaks among hospitalized patients in acute care settings: a systematic review,http://dx.doi.org/10.1186/s13643-015-0131-2,PMC4636845,26546048,CC BY,"BACKGROUND: Though often used to control outbreaks, the efficacy of ward closure is unclear. This systematic review sought to identify studies defining and describing ward closure in outbreak control and to determine impact of ward closure as an intervention on outbreak containment. METHODS: We searched these databases with no language restrictions: MEDLINE, 1946 to 7 July 2014; EMBASE, 1974 to 7 July 2014; CINAHL, 1937 to 8 July 2014; and Cochrane Database of Systematic Reviews, 2005 to May 2014. We also searched the following: IndMED; LILACS; reference lists from retrieved articles; conference proceedings; and websites of the CDCP, the ICID, and the WHO. We included studies of patients hospitalized in acute care facilities; used ward closure as a control measure; used other control measures; and discussed control of the outbreak(s) under investigation. A component approach was used to assess study quality. RESULTS: We included 97 English and non-English observational studies. None included a controlled comparison between ward closure and other interventions. We found that ward closure was often used as part of a bundle of interventions but could not determine its direct impact separate from all the other interventions whether used in parallel or in sequence with other interventions. We also found no universal definition of ward closure which was widely accepted. CONCLUSIONS: With no published controlled studies identified, ward closure for control of outbreaks remains an intervention that is not evidence based and healthcare personnel will need to continue to balance the competing risks associated with its use, taking into consideration the nature of the outbreak, the type of pathogen and its virulence, mode of transmission, and the setting in which it occurs. Our review has identified a major research gap in this area. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13643-015-0131-2) contains supplementary material, which is available to authorized users.",2015 Nov 7,"['Wong, Holly', 'Eso, Katherine', 'Ip, Ada', 'Jones, Jessica', 'Kwon, Yoojin', 'Powelson, Susan', 'de Grood, Jill', 'Geransar, Rose', 'Santana, Maria', 'Joffe, A. Mark', 'Taylor, Geoffrey', 'Missaghi, Bayan', 'Pearce, Craig', 'Ghali, William A.', 'Conly, John']",Syst Rev,,,True
8806dfedc1367125f90ab8479b99ae5a50438c1a,PMC,Viral Interference and Persistence in Mosquito-Borne Flaviviruses,http://dx.doi.org/10.1155/2015/873404,PMC4637105,26583158,CC BY,"Mosquito-borne flaviviruses are important pathogens for humans, and the detection of two or more flaviviruses cocirculating in the same geographic area has often been reported. However, the epidemiological impact remains to be determined. Mosquito-borne flaviviruses are primarily transmitted through Aedes and Culex mosquitoes; these viruses establish a life-long or persistent infection without apparent pathological effects. This establishment requires a balance between virus replication and the antiviral host response. Viral interference is a phenomenon whereby one virus inhibits the replication of other viruses, and this condition is frequently associated with persistent infections. Viral interference and persistent infection are determined by several factors, such as defective interfering particles, competition for cellular factors required for translation/replication, and the host antiviral response. The interaction between two flaviviruses typically results in viral interference, indicating that these viruses share common features during the replicative cycle in the vector. The potential mechanisms involved in these processes are reviewed here.",2015 Oct 25,"['Salas-Benito, Juan Santiago', 'De Nova-Ocampo, Mónica']",J Immunol Res,,,True
eb1b9685e0eaa51bef8c8a20729643d888e0a324,PMC,Pros and Cons of Antigen-Presenting Cell Targeted Tumor Vaccines,http://dx.doi.org/10.1155/2015/785634,PMC4637118,26583156,CC BY,"In therapeutic antitumor vaccination, dendritic cells play the leading role since they decide if, how, when, and where a potent antitumor immune response will take place. Since the disentanglement of the complexity and merit of different antigen-presenting cell subtypes, antitumor immunotherapeutic research started to investigate the potential benefit of targeting these subtypes in situ. This review will discuss which antigen-presenting cell subtypes are at play and how they have been targeted and finally question the true meaning of targeting antitumor-based vaccines.",2015 Oct 25,"['Goyvaerts, Cleo', 'Breckpot, Karine']",J Immunol Res,,,True
4e2c3b2b1b0da1299137c4193203f4aee8862eb3,PMC,Targeting vascular leakage in lung inflammation,,PMC4637277,26305720,CC BY,,2015 Jul 20,"['Li, Liang', 'Chow, Vincent T.K.', 'Tan, Nguan Soon']",Oncotarget,,,False
dfbdc96a5b50298935fd2f810339bdd055cb25fb,PMC,Regional health governance: A suggested agenda for Southern African health diplomacy,http://dx.doi.org/10.1177/1468018115599817,PMC4639828,26635498,CC BY,"Regional organisations can effectively promote regional health diplomacy and governance through engagement with regional social policy. Regional bodies make decisions about health challenges in the region, for example, the Union of South American Nations (UNASUR) and the World Health Organisation South East Asia Regional Office (WHO-SEARO). The Southern African Development Community (SADC) has a limited health presence as a regional organisation and diplomatic partner in health governance. This article identifies how SADC facilitates and coordinates health policy, arguing that SADC has the potential to promote regional health diplomacy and governance through engagement with regional social policy. The article identifies the role of global health diplomacy and niche diplomacy in health governance. The role of SADC as a regional organisation and the way it functions is then explained, focusing on how SADC engages with health issues in the region. Recommendations are made as to how SADC can play a more decisive role as a regional organisation to implement South–South management of the regional social policy, health governance and health diplomacy agenda.",2015 Dec,"['Penfold, Erica Dale', 'Fourie, Pieter']",Glob Soc Policy,,,True
32c89e23750b5dbc17e97eecfc5e916c15600ebe,PMC,"What’s in a word? The framing of health at the regional level: ASEAN, EU, SADC and UNASUR",http://dx.doi.org/10.1177/1468018115599816,PMC4639831,26635496,CC BY,"The Association of Southeast Asian Nations, the European Union, the Southern African Development Community and the Union of South American Nations have increasingly been involved in health diplomacy in the past decade, yet little is known about how they frame health as a foreign policy issue and how this has an impact on their prioritisation of policies. For this, we conducted a review of existing grey and peer-reviewed literature that address regional integration and health, as well as a documentary review according to security, development, trade, human rights, moral/ethical reasonings and global public goods frames identified in the literature. The policy frames identified responded to the challenges these regions currently face. The Association of Southeast Asian Nation’s struggle with re-emerging diseases has led to favouring a securitisation approach to health, the European Union approaches health as a cross-cutting policy issue, the Southern African Development Community presents health as a driver for development, and while the Union of South American Nations emphasises health as a human right and addresses the social determinants of health as an ethical imperative. Overall, these policy frames were useful in analysing the framing of health in foreign policy at the regional level. However, within our analysis, we identified a new frame that approaches health as an intersectoral issue. The impact of regional organisations’ forward will depend on their ability to harness their convening power and speak in a coherent voice on health matters.",2015 Dec,"['Amaya, Ana B', 'Rollet, Vincent', 'Kingah, Stephen']",Glob Soc Policy,,,True
c657f35b61e4e8e4ba9c06f72da78131608a4a85,PMC,Stretching health diplomacy beyond ‘Global’ problem solving: Bringing the regional normative dimension in,http://dx.doi.org/10.1177/1468018115599820,PMC4639834,26635500,CC BY,"The importance of the regional dimension of health diplomacy is only gaining slow and uneven recognition. This is in many ways surprising. As demonstrated in the work of Deacon on the ‘globalization of social policy’, global social policy has been animated and debated not only at the multilateral level but at the regional level as well. But at least in the diplomatic literature, the importance of this regional dynamic (with a focus on diverse sites and actors and the pursuit of democratic control) has been missed. The objective of this article is to explore whether health diplomacy is catching up to this larger debate re-shaping the conceptualization and practice of diplomacy more generally. In some ways, the results may be counter-productive in that this shift may encourage an increasingly fragmented process. Yet, it may also point to some breakthroughs, with diplomats, acting as ‘go to’ personnel on the front lines of operational activity, enabling actors to integrate with one another to produce effective governance. In doing so, the regional dimension is given greater recognition as a component of health diplomacy, albeit in an uneven and sometimes awkward manner. Whereas global diplomacy generally emphasizes problem solving, the regional dimension is animated by a normative orientation.",2015 Dec,"['Cooper, Andrew F', 'Farooq, Asif B']",Glob Soc Policy,,,True
4b0552782eeeefd0e22a8f2c7ff55351ec6f0c3a,PMC,A Simulation Study Comparing Epidemic Dynamics on Exponential Random Graph and Edge-Triangle Configuration Type Contact Network Models,http://dx.doi.org/10.1371/journal.pone.0142181,PMC4640514,26555701,CC BY,"We compare two broad types of empirically grounded random network models in terms of their abilities to capture both network features and simulated Susceptible-Infected-Recovered (SIR) epidemic dynamics. The types of network models are exponential random graph models (ERGMs) and extensions of the configuration model. We use three kinds of empirical contact networks, chosen to provide both variety and realistic patterns of human contact: a highly clustered network, a bipartite network and a snowball sampled network of a “hidden population”. In the case of the snowball sampled network we present a novel method for fitting an edge-triangle model. In our results, ERGMs consistently capture clustering as well or better than configuration-type models, but the latter models better capture the node degree distribution. Despite the additional computational requirements to fit ERGMs to empirical networks, the use of ERGMs provides only a slight improvement in the ability of the models to recreate epidemic features of the empirical network in simulated SIR epidemics. Generally, SIR epidemic results from using configuration-type models fall between those from a random network model (i.e., an Erdős-Rényi model) and an ERGM. The addition of subgraphs of size four to edge-triangle type models does improve agreement with the empirical network for smaller densities in clustered networks. Additional subgraphs do not make a noticeable difference in our example, although we would expect the ability to model cliques to be helpful for contact networks exhibiting household structure.",2015 Nov 10,"['Rolls, David A.', 'Wang, Peng', 'McBryde, Emma', 'Pattison, Philippa', 'Robins, Garry']",PLoS One,,,True
83649d575751ec9e3d8f1a8159da8c7f269fdc9f,PMC,A Simulation Study Comparing Epidemic Dynamics on Exponential Random Graph and Edge-Triangle Configuration Type Contact Network Models,http://dx.doi.org/10.1371/journal.pone.0142181,PMC4640514,26555701,CC BY,"We compare two broad types of empirically grounded random network models in terms of their abilities to capture both network features and simulated Susceptible-Infected-Recovered (SIR) epidemic dynamics. The types of network models are exponential random graph models (ERGMs) and extensions of the configuration model. We use three kinds of empirical contact networks, chosen to provide both variety and realistic patterns of human contact: a highly clustered network, a bipartite network and a snowball sampled network of a “hidden population”. In the case of the snowball sampled network we present a novel method for fitting an edge-triangle model. In our results, ERGMs consistently capture clustering as well or better than configuration-type models, but the latter models better capture the node degree distribution. Despite the additional computational requirements to fit ERGMs to empirical networks, the use of ERGMs provides only a slight improvement in the ability of the models to recreate epidemic features of the empirical network in simulated SIR epidemics. Generally, SIR epidemic results from using configuration-type models fall between those from a random network model (i.e., an Erdős-Rényi model) and an ERGM. The addition of subgraphs of size four to edge-triangle type models does improve agreement with the empirical network for smaller densities in clustered networks. Additional subgraphs do not make a noticeable difference in our example, although we would expect the ability to model cliques to be helpful for contact networks exhibiting household structure.",2015 Nov 10,"['Rolls, David A.', 'Wang, Peng', 'McBryde, Emma', 'Pattison, Philippa', 'Robins, Garry']",PLoS One,,,False
00af80743cef9bd8c04c532d74e9c67f0c9312e4,PMC,A Simulation Study Comparing Epidemic Dynamics on Exponential Random Graph and Edge-Triangle Configuration Type Contact Network Models,http://dx.doi.org/10.1371/journal.pone.0142181,PMC4640514,26555701,CC BY,"We compare two broad types of empirically grounded random network models in terms of their abilities to capture both network features and simulated Susceptible-Infected-Recovered (SIR) epidemic dynamics. The types of network models are exponential random graph models (ERGMs) and extensions of the configuration model. We use three kinds of empirical contact networks, chosen to provide both variety and realistic patterns of human contact: a highly clustered network, a bipartite network and a snowball sampled network of a “hidden population”. In the case of the snowball sampled network we present a novel method for fitting an edge-triangle model. In our results, ERGMs consistently capture clustering as well or better than configuration-type models, but the latter models better capture the node degree distribution. Despite the additional computational requirements to fit ERGMs to empirical networks, the use of ERGMs provides only a slight improvement in the ability of the models to recreate epidemic features of the empirical network in simulated SIR epidemics. Generally, SIR epidemic results from using configuration-type models fall between those from a random network model (i.e., an Erdős-Rényi model) and an ERGM. The addition of subgraphs of size four to edge-triangle type models does improve agreement with the empirical network for smaller densities in clustered networks. Additional subgraphs do not make a noticeable difference in our example, although we would expect the ability to model cliques to be helpful for contact networks exhibiting household structure.",2015 Nov 10,"['Rolls, David A.', 'Wang, Peng', 'McBryde, Emma', 'Pattison, Philippa', 'Robins, Garry']",PLoS One,,,True
cf27e2301131c5cb6d5b67e2dd29eff6f31ead18,PMC,A Simulation Study Comparing Epidemic Dynamics on Exponential Random Graph and Edge-Triangle Configuration Type Contact Network Models,http://dx.doi.org/10.1371/journal.pone.0142181,PMC4640514,26555701,CC BY,"We compare two broad types of empirically grounded random network models in terms of their abilities to capture both network features and simulated Susceptible-Infected-Recovered (SIR) epidemic dynamics. The types of network models are exponential random graph models (ERGMs) and extensions of the configuration model. We use three kinds of empirical contact networks, chosen to provide both variety and realistic patterns of human contact: a highly clustered network, a bipartite network and a snowball sampled network of a “hidden population”. In the case of the snowball sampled network we present a novel method for fitting an edge-triangle model. In our results, ERGMs consistently capture clustering as well or better than configuration-type models, but the latter models better capture the node degree distribution. Despite the additional computational requirements to fit ERGMs to empirical networks, the use of ERGMs provides only a slight improvement in the ability of the models to recreate epidemic features of the empirical network in simulated SIR epidemics. Generally, SIR epidemic results from using configuration-type models fall between those from a random network model (i.e., an Erdős-Rényi model) and an ERGM. The addition of subgraphs of size four to edge-triangle type models does improve agreement with the empirical network for smaller densities in clustered networks. Additional subgraphs do not make a noticeable difference in our example, although we would expect the ability to model cliques to be helpful for contact networks exhibiting household structure.",2015 Nov 10,"['Rolls, David A.', 'Wang, Peng', 'McBryde, Emma', 'Pattison, Philippa', 'Robins, Garry']",PLoS One,,,True
d7433f2be08b0e833cb270ee2ac736dce1e1a98e,PMC,A Simulation Study Comparing Epidemic Dynamics on Exponential Random Graph and Edge-Triangle Configuration Type Contact Network Models,http://dx.doi.org/10.1371/journal.pone.0142181,PMC4640514,26555701,CC BY,"We compare two broad types of empirically grounded random network models in terms of their abilities to capture both network features and simulated Susceptible-Infected-Recovered (SIR) epidemic dynamics. The types of network models are exponential random graph models (ERGMs) and extensions of the configuration model. We use three kinds of empirical contact networks, chosen to provide both variety and realistic patterns of human contact: a highly clustered network, a bipartite network and a snowball sampled network of a “hidden population”. In the case of the snowball sampled network we present a novel method for fitting an edge-triangle model. In our results, ERGMs consistently capture clustering as well or better than configuration-type models, but the latter models better capture the node degree distribution. Despite the additional computational requirements to fit ERGMs to empirical networks, the use of ERGMs provides only a slight improvement in the ability of the models to recreate epidemic features of the empirical network in simulated SIR epidemics. Generally, SIR epidemic results from using configuration-type models fall between those from a random network model (i.e., an Erdős-Rényi model) and an ERGM. The addition of subgraphs of size four to edge-triangle type models does improve agreement with the empirical network for smaller densities in clustered networks. Additional subgraphs do not make a noticeable difference in our example, although we would expect the ability to model cliques to be helpful for contact networks exhibiting household structure.",2015 Nov 10,"['Rolls, David A.', 'Wang, Peng', 'McBryde, Emma', 'Pattison, Philippa', 'Robins, Garry']",PLoS One,,,True
207f7aeed7a6907c94d4b00ed07e2ce3ded10ded,PMC,High Incidence of Mammalian Orthoreovirus Identified by Environmental Surveillance in Taiwan,http://dx.doi.org/10.1371/journal.pone.0142745,PMC4640864,26555962,CC BY,"Wild poliovirus (WPV) persists in diverse locales worldwide, spreading outward from endemic areas. In response to the international threat of WPV transmission and changes in the national vaccination policy, we established an environmental surveillance system to monitor the circulation of wild and vaccine-related poliovirus in Taiwan. From July 2012 to December 2013, we collected sewage specimens every month from 10 sewage treatment plants located throughout Taiwan. The specimens were concentrated by the two-phase separation method and then inoculated into L20B, RD, and A549 cells for virus isolation. Viral isolates were identified and serotyped by immunofluorescence assay or molecular analysis. A total of 300 sewage samples were collected, and the results showed 163 samples (54.3%) were positive for virus, and 268 isolates were identified. Among these, 75 samples (25%) were positive for enterovirus (EV), but no poliovirus was found. In addition, 92 isolates were identified as enteroviruses and the most common serotypes were coxsackievirus B4, coxsackievirus B3, and coxsackievirus B2. Interestingly, 102 (34%) and 82 (27.3%) specimens were positive for mammalian orthoreovirus (MRV) and adenovirus, respectively. This study confirmed that sewage surveillance can be a useful additional modality for monitoring the possible presence of wild-type or vaccine-derived poliovirus in wastewater, and can indicate the current types of viruses circulating in the population. Furthermore, since MRV was found in children with acute necrotizing encephalopathy and meningitis, the high incidence of MRV detected by environmental surveillance warrants further investigation.",2015 Nov 10,"['Lim, Matthew C. Y.', 'Wang, Ya-Fang', 'Huang, Sheng-Wen', 'Yang, Jyh-Yuan', 'Wang, Jen-Ren']",PLoS One,,,True
36e757c81ded2a278e917ab9030d1f682e4c4b9f,PMC,Pattern of patients and diseases during mass transit: The day of Arafat experience,http://dx.doi.org/10.12669/pjms.315.8017,PMC4641263,26648994,CC BY,"BACKGROUND AND OBJECTIVE: Every year 2-3 million Muslims gather for a few days around the Holy city of Makkah in Saudi Arabia to perform Hajj. Managing enormous health issues associated with such a mass gathering requires a very vibrant health delivery plan. Related research is part of the strategy. This study was done to assess the pattern of patients and illnesses encountered at one health facility at Arafat on the 2nd day of Hajj, when all the pilgrims move from Mina and stay in Arafat for a few hours. The objective of the study was to provide input so that recommendations can be given for future improvement of health care during this mass transit. METHODS: All patients reporting sick to the Nimra Hospital on the Day of Arafat were included and documented on a detailed Performa and analyzed. RESULTS: We received 211 patients, essentially all of those were in need of acute medical intervention. Acute severe asthma and injuries were the major problems encountered. There were two deaths both related to heat stroke. Patients received were predominantly Arabic speaking. CONCLUSIONS: Only those needing acute intervention seek medical advice during transit. Well equipped and staffed health facilities are, however, needed to cater these and for any mass casualties. Pre Hajj training and mandatory Flu vaccination can help.",2015 Sep-Oct,"['Sindy, Abdulfattah I.', 'Baljoon, Mostafa Jamil', 'Zubairi, Nadeem Alam', 'Dhafar, Khalid Obaid', 'Gazzaz, Zohair Jamil', 'Deiab, Basma Abdulhameed', 'Hothali, FauzeaTalea Al']",Pak J Med Sci,,,True
96e35195482d8911571c2242d612a317c7808caf,PMC,A census of α-helical membrane proteins in double-stranded DNA viruses infecting bacteria and archaea,http://dx.doi.org/10.1186/s12859-015-0817-4,PMC4641393,26554846,CC BY,"BACKGROUND: Viruses are the most abundant and genetically diverse biological entities on earth, yet the repertoire of viral proteins remains poorly explored. As the number of sequenced virus genomes grows into the thousands, and the number of viral proteins into the hundreds of thousands, we report a systematic computational analysis of the point of first-contact between viruses and their hosts, namely viral transmembrane (TM) proteins. RESULTS: The complement of α-helical TM proteins in double-stranded DNA viruses infecting bacteria and archaea reveals large-scale trends that differ from those of their hosts. Viruses typically encode a substantially lower fraction of TM proteins than archaea or bacteria, with the notable exception of viruses with virions containing a lipid component such as a lipid envelope, internal lipid core, or inner membrane vesicle. Compared to bacteriophages, archaeal viruses are substantially enriched in membrane proteins. However, this feature is not always stable throughout the evolution of a viral lineage; for example, TM proteins are not part of the common heritage shared between Lipothrixviridae and Rudiviridae. In contrast to bacteria and archaea, viruses almost completely lack proteins with complicated membrane topologies composed of more than 4 TM segments, with the few detected exceptions being obvious cases of relatively recent horizontal transfer from the host. CONCLUSIONS: The dramatic differences between the membrane proteomes of cells and viruses stem from the fact that viruses do not depend on essential membranes for energy transformation, ion homeostasis, nutrient transport and signaling. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0817-4) contains supplementary material, which is available to authorized users.",2015 Nov 10,"['Kristensen, David M.', 'Saeed, Usman', 'Frishman, Dmitrij', 'Koonin, Eugene V.']",BMC Bioinformatics,,,True
d0ad5a9116068caa5f78a95f8141a2a811662793,PMC,Modular approach to customise sample preparation procedures for viral metagenomics: a reproducible protocol for virome analysis,http://dx.doi.org/10.1038/srep16532,PMC4642273,26559140,CC BY,"A major limitation for better understanding the role of the human gut virome in health and disease is the lack of validated methods that allow high throughput virome analysis. To overcome this, we evaluated the quantitative effect of homogenisation, centrifugation, filtration, chloroform treatment and random amplification on a mock-virome (containing nine highly diverse viruses) and a bacterial mock-community (containing four faecal bacterial species) using quantitative PCR and next-generation sequencing. This resulted in an optimised protocol that was able to recover all viruses present in the mock-virome and strongly alters the ratio of viral versus bacterial and 16S rRNA genetic material in favour of viruses (from 43.2% to 96.7% viral reads and from 47.6% to 0.19% bacterial reads). Furthermore, our study indicated that most of the currently used virome protocols, using small filter pores and/or stringent centrifugation conditions may have largely overlooked large viruses present in viromes. We propose NetoVIR (Novel enrichment technique of VIRomes), which allows for a fast, reproducible and high throughput sample preparation for viral metagenomics studies, introducing minimal bias. This procedure is optimised mainly for faecal samples, but with appropriate concentration steps can also be used for other sample types with lower initial viral loads.",2015 Nov 12,"['Conceição-Neto, Nádia', 'Zeller, Mark', 'Lefrère, Hanne', 'De Bruyn, Pieter', 'Beller, Leen', 'Deboutte, Ward', 'Yinda, Claude Kwe', 'Lavigne, Rob', 'Maes, Piet', 'Ranst, Marc Van', 'Heylen, Elisabeth', 'Matthijnssens, Jelle']",Sci Rep,,,True
6f14312d95463d446d7f58d981a725f9efe2b5b4,PMC,Modular approach to customise sample preparation procedures for viral metagenomics: a reproducible protocol for virome analysis,http://dx.doi.org/10.1038/srep16532,PMC4642273,26559140,CC BY,"A major limitation for better understanding the role of the human gut virome in health and disease is the lack of validated methods that allow high throughput virome analysis. To overcome this, we evaluated the quantitative effect of homogenisation, centrifugation, filtration, chloroform treatment and random amplification on a mock-virome (containing nine highly diverse viruses) and a bacterial mock-community (containing four faecal bacterial species) using quantitative PCR and next-generation sequencing. This resulted in an optimised protocol that was able to recover all viruses present in the mock-virome and strongly alters the ratio of viral versus bacterial and 16S rRNA genetic material in favour of viruses (from 43.2% to 96.7% viral reads and from 47.6% to 0.19% bacterial reads). Furthermore, our study indicated that most of the currently used virome protocols, using small filter pores and/or stringent centrifugation conditions may have largely overlooked large viruses present in viromes. We propose NetoVIR (Novel enrichment technique of VIRomes), which allows for a fast, reproducible and high throughput sample preparation for viral metagenomics studies, introducing minimal bias. This procedure is optimised mainly for faecal samples, but with appropriate concentration steps can also be used for other sample types with lower initial viral loads.",2015 Nov 12,"['Conceição-Neto, Nádia', 'Zeller, Mark', 'Lefrère, Hanne', 'De Bruyn, Pieter', 'Beller, Leen', 'Deboutte, Ward', 'Yinda, Claude Kwe', 'Lavigne, Rob', 'Maes, Piet', 'Ranst, Marc Van', 'Heylen, Elisabeth', 'Matthijnssens, Jelle']",Sci Rep,,,False
055bc4fbdbbe262da7684e89ea4cfcc154a42291,PMC,Self-reactive CD4(+) T cells activated during viral-induced demyelination do not prevent clinical recovery,http://dx.doi.org/10.1186/s12974-015-0426-1,PMC4642610,26559484,CC BY,"BACKGROUND: Microbial infections have been implicated in initiating and enhancing severity of autoimmune diseases including the demyelinating disease multiple sclerosis (MS). Nevertheless, the incidence of both acute and persisting viral infections without evidence of autoimmune sequelae suggests that this process is well controlled. The conditions promoting or stemming self-reactive (SR) T cells following viral-induced tissue damage thus need to be better defined. Using a non-fatal viral mouse model of encephalomyelitis associated with demyelination and disability, yet ultimate clinical improvement, this study set out to monitor uptake and presentation of endogenous myelin antigens, as well as induction and fate of SR T cells. METHODS: Activation and central nervous system (CNS) recruitment of myelin-specific CD4 T cells was analyzed by flow cytometry during encephalomyelitis induced by a glia tropic murine coronavirus. Potential antigen-presenting cells (APC) ingesting myelin were characterized by flow cytometry and their ability to activate SR T cells tested by co-culture with carboxyfluorescein succinimidyl ester (CFSE)-labeled myelin-specific CD4 T cells. Endogenous SR T cell kinetics was analyzed within both cervical lymph nodes and CNS by Enzyme-Linked ImmunoSpot (ELISPOT) following viral infection. RESULTS: The data demonstrate the presence of APC capable of activating SR T cells in both draining lymph nodes and the CNS temporally correlating with overt demyelination. While both the CNS-infiltrating myeloid population and microglia ingested myelin, only CNS-infiltrating APC were capable of presenting endogenous myelin antigen to SR T cells ex vivo. Finally, SR T cell activation from the endogenous T cell repertoire was most notable when infectious virus was controlled and paralleled myelin damage. Although SR T cell accumulation peaked in the persistently infected CNS during maximal demyelination, they were not preferentially retained. Their gradual decline, despite ongoing demyelination, suggested minimal re-stimulation and pathogenic function in vivo consistent with the lack of autoimmune symptoms. CONCLUSIONS: The results demonstrate the potential for CNS tissue destruction to induce and recruit SR T cells to the injury site and support a host suppressive mechanism limiting development of autoimmunity.",2015 Nov 11,"['Savarin, Carine', 'Bergmann, Cornelia C.', 'Gaignage, Melanie', 'Stohlman, Stephen A.']",J Neuroinflammation,,,True
015a5be4701f244a51d6c244c2ba5b69ac68dd9d,PMC,Interferon-γ Inhibits Ebola Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1005263,PMC4643030,26562011,CC BY,"Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.",2015 Nov 12,"['Rhein, Bethany A.', 'Powers, Linda S.', 'Rogers, Kai', 'Anantpadma, Manu', 'Singh, Brajesh K.', 'Sakurai, Yasuteru', 'Bair, Thomas', 'Miller-Hunt, Catherine', 'Sinn, Patrick', 'Davey, Robert A.', 'Monick, Martha M.', 'Maury, Wendy']",PLoS Pathog,,,True
ec9faa32c45199e8fec10c7a0d3bae3dd0275744,PMC,"Phylogenetic Exploration of Nosocomial Transmission Chains of 2009 Influenza A/H1N1 among Children Admitted at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa in 2011",http://dx.doi.org/10.1371/journal.pone.0141744,PMC4643913,26565994,CC BY,"Traditional modes of investigating influenza nosocomial transmission have entailed a combination of confirmatory molecular diagnostic testing and epidemiological investigation. Common hospital-acquired infections like influenza require a discerning ability to distinguish between viral isolates to accurately identify patient transmission chains. We assessed whether influenza hemagglutinin sequence phylogenies can be used to enrich epidemiological data when investigating the extent of nosocomial transmission over a four-month period within a paediatric Hospital in Cape Town South Africa. Possible transmission chains/channels were initially determined through basic patient admission data combined with Maximum likelihood and time-scaled Bayesian phylogenetic analyses. These analyses suggested that most instances of potential hospital-acquired infections resulted from multiple introductions of Influenza A into the hospital, which included instances where virus hemagglutinin sequences were identical between different patients. Furthermore, a general inability to establish epidemiological transmission linkage of patients/viral isolates implied that identified isolates could have originated from asymptomatic hospital patients, visitors or hospital staff. In contrast, a traditional epidemiological investigation that used no viral phylogenetic analyses, based on patient co-admission into specific wards during a particular time-frame, suggested that multiple hospital acquired infection instances may have stemmed from a limited number of identifiable index viral isolates/patients. This traditional epidemiological analysis by itself could incorrectly suggest linkage between unrelated cases, underestimate the number of unique infections and may overlook the possible diffuse nature of hospital transmission, which was suggested by sequencing data to be caused by multiple unique introductions of influenza A isolates into individual hospital wards. We have demonstrated a functional role for viral sequence data in nosocomial transmission investigation through its ability to enrich traditional, non-molecular observational epidemiological investigation by teasing out possible transmission pathways and working toward more accurately enumerating the number of possible transmission events.",2015 Nov 13,"['Valley-Omar, Ziyaad', 'Nindo, Fredrick', 'Mudau, Maanda', 'Hsiao, Marvin', 'Martin, Darren Patrick']",PLoS One,,,True
082c4a3189859a27a7828ebdaffad450896216bc,PMC,"Phylogenetic Exploration of Nosocomial Transmission Chains of 2009 Influenza A/H1N1 among Children Admitted at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa in 2011",http://dx.doi.org/10.1371/journal.pone.0141744,PMC4643913,26565994,CC BY,"Traditional modes of investigating influenza nosocomial transmission have entailed a combination of confirmatory molecular diagnostic testing and epidemiological investigation. Common hospital-acquired infections like influenza require a discerning ability to distinguish between viral isolates to accurately identify patient transmission chains. We assessed whether influenza hemagglutinin sequence phylogenies can be used to enrich epidemiological data when investigating the extent of nosocomial transmission over a four-month period within a paediatric Hospital in Cape Town South Africa. Possible transmission chains/channels were initially determined through basic patient admission data combined with Maximum likelihood and time-scaled Bayesian phylogenetic analyses. These analyses suggested that most instances of potential hospital-acquired infections resulted from multiple introductions of Influenza A into the hospital, which included instances where virus hemagglutinin sequences were identical between different patients. Furthermore, a general inability to establish epidemiological transmission linkage of patients/viral isolates implied that identified isolates could have originated from asymptomatic hospital patients, visitors or hospital staff. In contrast, a traditional epidemiological investigation that used no viral phylogenetic analyses, based on patient co-admission into specific wards during a particular time-frame, suggested that multiple hospital acquired infection instances may have stemmed from a limited number of identifiable index viral isolates/patients. This traditional epidemiological analysis by itself could incorrectly suggest linkage between unrelated cases, underestimate the number of unique infections and may overlook the possible diffuse nature of hospital transmission, which was suggested by sequencing data to be caused by multiple unique introductions of influenza A isolates into individual hospital wards. We have demonstrated a functional role for viral sequence data in nosocomial transmission investigation through its ability to enrich traditional, non-molecular observational epidemiological investigation by teasing out possible transmission pathways and working toward more accurately enumerating the number of possible transmission events.",2015 Nov 13,"['Valley-Omar, Ziyaad', 'Nindo, Fredrick', 'Mudau, Maanda', 'Hsiao, Marvin', 'Martin, Darren Patrick']",PLoS One,,,False
5bd0d5db60f72689e429b6f1e98678d789930366,PMC,Early-Life Exposure to Clostridium leptum Causes Pulmonary Immunosuppression,http://dx.doi.org/10.1371/journal.pone.0141717,PMC4643994,26565810,CC BY,"INTRODUCTION: Low Clostridium leptum levels are a risk factor for the development of asthma. C. leptum deficiency exacerbates asthma; however, the impact of early-life C. leptum exposure on cesarean-delivered mice remains unclear. This study is to determine the effects of early-life C. leptum exposure on asthma development in infant mice. METHODS: We exposed infant mice to C. leptum (fed-CL) and then induced asthma using the allergen ovalbumin (OVA). RESULTS: Fed-CL increased regulatory T (Treg) cells in cesarean-delivered mice compared with vaginally delivered mice. Compared with OVA-exposed mice, mice exposed to C. leptum + OVA did not develop the typical asthma phenotype, which includes airway hyper-responsiveness, cell infiltration, and T helper cell subset (Th1, Th2, Th9, Th17) inflammation. Early-life C. leptum exposure induced an immunosuppressive environment in the lung concurrent with increased Treg cells, resulting in the inhibition of Th1, Th2, Th9, and Th17 cell responses. CONCLUSION: These findings demonstrate a mechanism whereby C. leptum exposure modulates adaptive immunity and leads to failure to develop asthma upon OVA sensitization later in life.",2015 Nov 13,"['Huang, Fei', 'Qiao, Hong-mei', 'Yin, Jia-ning', 'Gao, Yang', 'Ju, Yang-hua', 'Li, Ya-nan']",PLoS One,,,True
e8ae9d6178f8322e2f9b2453ef13bb312427bd15,PMC,Identify-Isolate-Inform: A Modified Tool for Initial Detection and Management of Middle East Respiratory Syndrome Patients in the Emergency Department,http://dx.doi.org/10.5811/westjem.2015.7.27915,PMC4644025,26587081,CC BY,"Middle East respiratory syndrome (MERS) is a novel infectious disease caused by a coronavirus (MERS-CoV) first reported in Saudi Arabia in September 2012. MERS later spread to other countries in the Arabian Peninsula, followed by an outbreak in South Korea in 2015. At least 26 countries have reported MERS cases, and these numbers may increase over time. Due to international travel opportunities, all countries are at risk of imported cases of MERS, even if outbreaks do not spread globally. Therefore, it is essential for emergency department (ED) personnel to be able to rapidly assess MERS risk and take immediate actions if indicated. The Identify-Isolate-Inform (3I) tool, originally conceived for initial detection and management of Ebola virus disease patients in the ED and later adjusted for measles, can be adapted for real-time use for any emerging infectious disease. This paper reports a modification of the 3I tool for use in initial detection and management of patients under investigation for MERS. Following an assessment of epidemiologic risk factors, including travel to countries with current MERS transmission and contact with patients with confirmed MERS within 14 days, patients are risk stratified by type of exposure coupled with symptoms of fever and respiratory illness. If criteria are met, patients must be immediately placed into airborne infection isolation (or a private room until this type of isolation is available) and the emergency practitioner must alert the hospital infection prevention and control team and the local public health department. The 3I tool will facilitate rapid categorization and triggering of appropriate time-sensitive actions for patients presenting to the ED at risk for MERS.",2015 Sep 20,"Koenig, Kristi L.",West J Emerg Med,,,True
f55b841ff2d5939a229e9a7053d26e48b5139610,PMC,Viral and bacterial etiology of severe acute respiratory illness among children < 5 years of age without influenza in Niger,http://dx.doi.org/10.1186/s12879-015-1251-y,PMC4644278,26567015,CC BY,"BACKGROUND: Globally, pneumonia is the leading cause of morbidity and mortality in children, with the highest burden experienced in sub-Saharan Africa and Asia. However, there is a dearth of information on the etiology of severe acute respiratory illness (SARI) in Africa, including Niger. METHODS: We implemented a retrospective study as part of national influenza sentinel surveillance in Niger. We randomly selected a sample of nasopharyngeal specimens collected from children <5 years of age hospitalized with SARI from January 2010 through December 2012 in Niger. The samples were selected from individuals that tested negative by real-time reverse transcription polymerase chain reaction (rRT-PCR) for influenza A and B virus. The samples were analyzed using the Fast Track Diagnostic Respiratory Pathogens 21plus Kit (BioMérieux, Luxemburg), which detects 23 respiratory pathogens including 18 viral and 5 bacterial agents. RESULTS: Among the 160 samples tested, 138 (86 %) tested positive for at least one viral or bacterial pathogen; in 22 (16 %) sample, only one pathogen was detected. We detected at least one respiratory virus in 126 (78 %) samples and at least one bacterium in 102 (64 %) samples. Respiratory syncytial virus (56/160; 35 %), rhinovirus (47/160; 29 %) and parainfluenza virus (39/160; 24 %) were the most common viral pathogens detected. Among bacterial pathogens, Streptococcus pneumoniae (90/160; 56 %) and Haemophilus influenzae type b (20/160; 12 %) predominated. CONCLUSIONS: The high prevalence of certain viral and bacterial pathogens among children <5 years of age with SARI highlights the need for continued and expanded surveillance in Niger.",2015 Nov 14,"['Lagare, Adamou', 'Maïnassara, Halima Boubacar', 'Issaka, Bassira', 'Sidiki, Ali', 'Tempia, Stefano']",BMC Infect Dis,,,True
b39a7ae61df099ef77e90893f0ae87a6b63b6586,PMC,Feline calicivirus and other respiratory pathogens in cats with Feline calicivirus-related symptoms and in clinically healthy cats in Switzerland,http://dx.doi.org/10.1186/s12917-015-0595-2,PMC4644299,26566897,CC BY,"BACKGROUND: Cats with feline calicivirus (FCV)-related symptoms are commonly presented to veterinary practitioners. Various clinical manifestations have been attributed to FCV, i.e. upper respiratory tract disease (URTD), oral ulcerations, gingivostomatitis, limping syndrome and virulent systemic disease. Additionally, healthy cats can shed FCV. The aims of this study were 1) to investigate the frequency of FCV in cats with FCV-related symptoms and in healthy cats in Switzerland, 2) to assess risk and protective factors for infection, such as signalment, housing conditions, vaccination, and co-infection with URTD-associated pathogens, and 3) to address the association between clinical symptoms and FCV infection. RESULTS: Oropharyngeal, nasal and conjunctival swabs were collected in 24 veterinary practices from 200 FCV-suspect and 100 healthy cats originating from 19 cantons of Switzerland. The samples were tested for FCV using virus isolation and reverse-transcription real-time quantitative polymerase chain reaction (qPCR) and for feline herpesvirus-1 (FHV-1), Mycoplasma felis, Chlamydophila felis, Bordetella bronchiseptica using real-time qPCR. Within the two populations (FCV-suspect/healthy), the observed PCR prevalences were: FCV 45 %/8 %, FHV-1 20 %/9 %, C. felis 8 %/1 %, B. bronchiseptica 4 %/2 %, M. felis 47 %/31 % and any co-infections thereof 40 %/14 %. Based on multivariable regression models amongst FCV-suspect cats (odds ratio [95 % confidence interval]), co-infection with M. felis (1.75 [0.97; 3.14]), group housing (2.11 [1.02; 4.34]) and intact reproductive status (1.80 [0.99; 3.28]) were found to be risk factors for FCV infection. In healthy cats, intact reproductive status (22.2 [1.85; 266.7]) and group housing (46.4 [5.70; 377.7]) were found to be associated with FCV infection. Based on an univariable approach, FCV-suspect cats were found to be significantly less often FCV-positive when vaccinated (0.48 [0.24; 0.94]). Oral ulcerations, salivation, gingivitis and stomatitis, but not classical signs of URTD were significantly associated with FCV infection (all p < 0.001). CONCLUSIONS: FCV was detected in less than half of the cats that were judged FCV-suspect by veterinary practitioners. For a clinical diagnosis, FCV-related symptoms should be revisited. FCV infection was present in some healthy cats, underlining the importance of asymptomatic carriers in FCV epidemiology. To reduce FCV-related problems in multi-cat environments, reduction of group size in addition to the generally recommended vaccination are advocated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0595-2) contains supplementary material, which is available to authorized users.",2015 Nov 13,"['Berger, Alice', 'Willi, Barbara', 'Meli, Marina L.', 'Boretti, Felicitas S.', 'Hartnack, Sonja', 'Dreyfus, Anou', 'Lutz, Hans', 'Hofmann-Lehmann, Regina']",BMC Vet Res,,,False
51efc4963ed83855fd6163713ebdbdbee66cbee9,PMC,Feline calicivirus and other respiratory pathogens in cats with Feline calicivirus-related symptoms and in clinically healthy cats in Switzerland,http://dx.doi.org/10.1186/s12917-015-0595-2,PMC4644299,26566897,CC BY,"BACKGROUND: Cats with feline calicivirus (FCV)-related symptoms are commonly presented to veterinary practitioners. Various clinical manifestations have been attributed to FCV, i.e. upper respiratory tract disease (URTD), oral ulcerations, gingivostomatitis, limping syndrome and virulent systemic disease. Additionally, healthy cats can shed FCV. The aims of this study were 1) to investigate the frequency of FCV in cats with FCV-related symptoms and in healthy cats in Switzerland, 2) to assess risk and protective factors for infection, such as signalment, housing conditions, vaccination, and co-infection with URTD-associated pathogens, and 3) to address the association between clinical symptoms and FCV infection. RESULTS: Oropharyngeal, nasal and conjunctival swabs were collected in 24 veterinary practices from 200 FCV-suspect and 100 healthy cats originating from 19 cantons of Switzerland. The samples were tested for FCV using virus isolation and reverse-transcription real-time quantitative polymerase chain reaction (qPCR) and for feline herpesvirus-1 (FHV-1), Mycoplasma felis, Chlamydophila felis, Bordetella bronchiseptica using real-time qPCR. Within the two populations (FCV-suspect/healthy), the observed PCR prevalences were: FCV 45 %/8 %, FHV-1 20 %/9 %, C. felis 8 %/1 %, B. bronchiseptica 4 %/2 %, M. felis 47 %/31 % and any co-infections thereof 40 %/14 %. Based on multivariable regression models amongst FCV-suspect cats (odds ratio [95 % confidence interval]), co-infection with M. felis (1.75 [0.97; 3.14]), group housing (2.11 [1.02; 4.34]) and intact reproductive status (1.80 [0.99; 3.28]) were found to be risk factors for FCV infection. In healthy cats, intact reproductive status (22.2 [1.85; 266.7]) and group housing (46.4 [5.70; 377.7]) were found to be associated with FCV infection. Based on an univariable approach, FCV-suspect cats were found to be significantly less often FCV-positive when vaccinated (0.48 [0.24; 0.94]). Oral ulcerations, salivation, gingivitis and stomatitis, but not classical signs of URTD were significantly associated with FCV infection (all p < 0.001). CONCLUSIONS: FCV was detected in less than half of the cats that were judged FCV-suspect by veterinary practitioners. For a clinical diagnosis, FCV-related symptoms should be revisited. FCV infection was present in some healthy cats, underlining the importance of asymptomatic carriers in FCV epidemiology. To reduce FCV-related problems in multi-cat environments, reduction of group size in addition to the generally recommended vaccination are advocated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0595-2) contains supplementary material, which is available to authorized users.",2015 Nov 13,"['Berger, Alice', 'Willi, Barbara', 'Meli, Marina L.', 'Boretti, Felicitas S.', 'Hartnack, Sonja', 'Dreyfus, Anou', 'Lutz, Hans', 'Hofmann-Lehmann, Regina']",BMC Vet Res,,,False
d7d55a2878914bb8041ddc930789df1344cb940b,PMC,Feline calicivirus and other respiratory pathogens in cats with Feline calicivirus-related symptoms and in clinically healthy cats in Switzerland,http://dx.doi.org/10.1186/s12917-015-0595-2,PMC4644299,26566897,CC BY,"BACKGROUND: Cats with feline calicivirus (FCV)-related symptoms are commonly presented to veterinary practitioners. Various clinical manifestations have been attributed to FCV, i.e. upper respiratory tract disease (URTD), oral ulcerations, gingivostomatitis, limping syndrome and virulent systemic disease. Additionally, healthy cats can shed FCV. The aims of this study were 1) to investigate the frequency of FCV in cats with FCV-related symptoms and in healthy cats in Switzerland, 2) to assess risk and protective factors for infection, such as signalment, housing conditions, vaccination, and co-infection with URTD-associated pathogens, and 3) to address the association between clinical symptoms and FCV infection. RESULTS: Oropharyngeal, nasal and conjunctival swabs were collected in 24 veterinary practices from 200 FCV-suspect and 100 healthy cats originating from 19 cantons of Switzerland. The samples were tested for FCV using virus isolation and reverse-transcription real-time quantitative polymerase chain reaction (qPCR) and for feline herpesvirus-1 (FHV-1), Mycoplasma felis, Chlamydophila felis, Bordetella bronchiseptica using real-time qPCR. Within the two populations (FCV-suspect/healthy), the observed PCR prevalences were: FCV 45 %/8 %, FHV-1 20 %/9 %, C. felis 8 %/1 %, B. bronchiseptica 4 %/2 %, M. felis 47 %/31 % and any co-infections thereof 40 %/14 %. Based on multivariable regression models amongst FCV-suspect cats (odds ratio [95 % confidence interval]), co-infection with M. felis (1.75 [0.97; 3.14]), group housing (2.11 [1.02; 4.34]) and intact reproductive status (1.80 [0.99; 3.28]) were found to be risk factors for FCV infection. In healthy cats, intact reproductive status (22.2 [1.85; 266.7]) and group housing (46.4 [5.70; 377.7]) were found to be associated with FCV infection. Based on an univariable approach, FCV-suspect cats were found to be significantly less often FCV-positive when vaccinated (0.48 [0.24; 0.94]). Oral ulcerations, salivation, gingivitis and stomatitis, but not classical signs of URTD were significantly associated with FCV infection (all p < 0.001). CONCLUSIONS: FCV was detected in less than half of the cats that were judged FCV-suspect by veterinary practitioners. For a clinical diagnosis, FCV-related symptoms should be revisited. FCV infection was present in some healthy cats, underlining the importance of asymptomatic carriers in FCV epidemiology. To reduce FCV-related problems in multi-cat environments, reduction of group size in addition to the generally recommended vaccination are advocated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0595-2) contains supplementary material, which is available to authorized users.",2015 Nov 13,"['Berger, Alice', 'Willi, Barbara', 'Meli, Marina L.', 'Boretti, Felicitas S.', 'Hartnack, Sonja', 'Dreyfus, Anou', 'Lutz, Hans', 'Hofmann-Lehmann, Regina']",BMC Vet Res,,,False
3dc77148a29d1caf25a7a345f04d61d160385734,PMC,Feline calicivirus and other respiratory pathogens in cats with Feline calicivirus-related symptoms and in clinically healthy cats in Switzerland,http://dx.doi.org/10.1186/s12917-015-0595-2,PMC4644299,26566897,CC BY,"BACKGROUND: Cats with feline calicivirus (FCV)-related symptoms are commonly presented to veterinary practitioners. Various clinical manifestations have been attributed to FCV, i.e. upper respiratory tract disease (URTD), oral ulcerations, gingivostomatitis, limping syndrome and virulent systemic disease. Additionally, healthy cats can shed FCV. The aims of this study were 1) to investigate the frequency of FCV in cats with FCV-related symptoms and in healthy cats in Switzerland, 2) to assess risk and protective factors for infection, such as signalment, housing conditions, vaccination, and co-infection with URTD-associated pathogens, and 3) to address the association between clinical symptoms and FCV infection. RESULTS: Oropharyngeal, nasal and conjunctival swabs were collected in 24 veterinary practices from 200 FCV-suspect and 100 healthy cats originating from 19 cantons of Switzerland. The samples were tested for FCV using virus isolation and reverse-transcription real-time quantitative polymerase chain reaction (qPCR) and for feline herpesvirus-1 (FHV-1), Mycoplasma felis, Chlamydophila felis, Bordetella bronchiseptica using real-time qPCR. Within the two populations (FCV-suspect/healthy), the observed PCR prevalences were: FCV 45 %/8 %, FHV-1 20 %/9 %, C. felis 8 %/1 %, B. bronchiseptica 4 %/2 %, M. felis 47 %/31 % and any co-infections thereof 40 %/14 %. Based on multivariable regression models amongst FCV-suspect cats (odds ratio [95 % confidence interval]), co-infection with M. felis (1.75 [0.97; 3.14]), group housing (2.11 [1.02; 4.34]) and intact reproductive status (1.80 [0.99; 3.28]) were found to be risk factors for FCV infection. In healthy cats, intact reproductive status (22.2 [1.85; 266.7]) and group housing (46.4 [5.70; 377.7]) were found to be associated with FCV infection. Based on an univariable approach, FCV-suspect cats were found to be significantly less often FCV-positive when vaccinated (0.48 [0.24; 0.94]). Oral ulcerations, salivation, gingivitis and stomatitis, but not classical signs of URTD were significantly associated with FCV infection (all p < 0.001). CONCLUSIONS: FCV was detected in less than half of the cats that were judged FCV-suspect by veterinary practitioners. For a clinical diagnosis, FCV-related symptoms should be revisited. FCV infection was present in some healthy cats, underlining the importance of asymptomatic carriers in FCV epidemiology. To reduce FCV-related problems in multi-cat environments, reduction of group size in addition to the generally recommended vaccination are advocated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0595-2) contains supplementary material, which is available to authorized users.",2015 Nov 13,"['Berger, Alice', 'Willi, Barbara', 'Meli, Marina L.', 'Boretti, Felicitas S.', 'Hartnack, Sonja', 'Dreyfus, Anou', 'Lutz, Hans', 'Hofmann-Lehmann, Regina']",BMC Vet Res,,,True
7697fcf19fb5548783f66563f33f7977ff59cd7a,PMC,Are Microglial Cells the Regulators of Lymphocyte Responses in the CNS?,http://dx.doi.org/10.3389/fncel.2015.00440,PMC4644801,26635525,CC BY,"The infiltration of immune cells in the central nervous system is a common hallmark in different neuroinflammatory conditions. Accumulating evidence indicates that resident glial cells can establish a cross-talk with infiltrated immune cells, including T-cells, regulating their recruitment, activation and function within the CNS. Although the healthy CNS has been thought to be devoid of professional dendritic cells (DCs), numerous studies have reported the presence of a population of DCs in specific locations such as the meninges, choroid plexuses and the perivascular space. Moreover, the infiltration of DC precursors during neuroinflammatory situations has been proposed, suggesting a putative role of these cells in the regulation of lymphocyte activity within the CNS. On the other hand, under specific circumstances, microglial cells are able to acquire a phenotype of DC expressing a wide range of molecules that equip these cells with all the necessary machinery for communication with T-cells. In this review, we summarize the current knowledge on the expression of molecules involved in the cross-talk with T-cells in both microglial cells and DCs and discuss the potential contribution of each of these cell populations on the control of lymphocyte function within the CNS.",2015 Nov 16,"['Almolda, Beatriz', 'González, Berta', 'Castellano, Bernardo']",Front Cell Neurosci,,,True
6f59c51ced3b52352e02cb226a542900b94ef5f5,PMC,Modeling [(18)F]-FDG lymphoid tissue kinetics to characterize nonhuman primate immune response to Middle East respiratory syndrome-coronavirus aerosol challenge,http://dx.doi.org/10.1186/s13550-015-0143-x,PMC4646887,26573211,CC BY,"BACKGROUND: The pathogenesis and immune response to Middle East respiratory syndrome (MERS) caused by a recently discovered coronavirus, MERS-CoV, have not been fully characterized because a suitable animal model is currently not available. (18)F-Fluorodeoxyglucose ([(18)F]-FDG)-positron emission tomography/computed tomography (PET/CT) as a longitudinal noninvasive approach can be beneficial in providing biomarkers for host immune response. [(18)F]-FDG uptake is increased in activated immune cells in response to virus entry and can be localized by PET imaging. We used [(18)F]-FDG-PET/CT to investigate the host response developing in nonhuman primates after MERS-CoV exposure and applied kinetic modeling to monitor the influx rate constant (K(i)) in responsive lymphoid tissue. METHODS: Multiple [(18)F]-FDG-PET and CT images were acquired on a PET/CT clinical scanner modified to operate in a biosafety level 4 environment prior to and up to 29 days after MERS-CoV aerosol exposure. Time activity curves of various lymphoid tissues were reconstructed to follow the [(18)F]-FDG uptake for approximately 60 min (3,600 s). Image-derived input function was used to calculate K(i) for lymphoid tissues by Patlak plot. RESULTS: Two-way repeated measures analysis of variance revealed alterations in K(i) that was associated with the time point (p < 0.001) after virus exposure and the location of lymphoid tissue (p = 0.0004). As revealed by a statistically significant interaction (p < 0.0001) between these two factors, the pattern of K(i) changes over time differed between three locations but not between subjects. A distinguished pattern of statistically significant elevation in K(i) was observed in mediastinal lymph nodes (LNs) that correlated to K(i) changes in axillary LNs. Changes in LNs K(i) were concurrent with elevations of monocytes in peripheral blood. CONCLUSIONS: [(18)F]-FDG-PET is able to detect subtle changes in host immune response to contain a subclinical virus infection. Full quantitative analysis is the preferred approach rather than semiquantitative analysis using standardized uptake value for detection of the immune response to the virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13550-015-0143-x) contains supplementary material, which is available to authorized users.",2015 Nov 16,"['Chefer, Svetlana', 'Thomasson, David', 'Seidel, Jurgen', 'Reba, Richard C.', 'Bohannon, J. Kyle', 'Lackemeyer, Mathew G.', 'Bartos, Chris', 'Sayre, Philip J.', 'Bollinger, Laura', 'Hensley, Lisa E.', 'Jahrling, Peter B.', 'Johnson, Reed F.']",EJNMMI Res,,,False
f2f841111913d49cbbd17e0988fc4f49b06c4945,PMC,Modeling [(18)F]-FDG lymphoid tissue kinetics to characterize nonhuman primate immune response to Middle East respiratory syndrome-coronavirus aerosol challenge,http://dx.doi.org/10.1186/s13550-015-0143-x,PMC4646887,26573211,CC BY,"BACKGROUND: The pathogenesis and immune response to Middle East respiratory syndrome (MERS) caused by a recently discovered coronavirus, MERS-CoV, have not been fully characterized because a suitable animal model is currently not available. (18)F-Fluorodeoxyglucose ([(18)F]-FDG)-positron emission tomography/computed tomography (PET/CT) as a longitudinal noninvasive approach can be beneficial in providing biomarkers for host immune response. [(18)F]-FDG uptake is increased in activated immune cells in response to virus entry and can be localized by PET imaging. We used [(18)F]-FDG-PET/CT to investigate the host response developing in nonhuman primates after MERS-CoV exposure and applied kinetic modeling to monitor the influx rate constant (K(i)) in responsive lymphoid tissue. METHODS: Multiple [(18)F]-FDG-PET and CT images were acquired on a PET/CT clinical scanner modified to operate in a biosafety level 4 environment prior to and up to 29 days after MERS-CoV aerosol exposure. Time activity curves of various lymphoid tissues were reconstructed to follow the [(18)F]-FDG uptake for approximately 60 min (3,600 s). Image-derived input function was used to calculate K(i) for lymphoid tissues by Patlak plot. RESULTS: Two-way repeated measures analysis of variance revealed alterations in K(i) that was associated with the time point (p < 0.001) after virus exposure and the location of lymphoid tissue (p = 0.0004). As revealed by a statistically significant interaction (p < 0.0001) between these two factors, the pattern of K(i) changes over time differed between three locations but not between subjects. A distinguished pattern of statistically significant elevation in K(i) was observed in mediastinal lymph nodes (LNs) that correlated to K(i) changes in axillary LNs. Changes in LNs K(i) were concurrent with elevations of monocytes in peripheral blood. CONCLUSIONS: [(18)F]-FDG-PET is able to detect subtle changes in host immune response to contain a subclinical virus infection. Full quantitative analysis is the preferred approach rather than semiquantitative analysis using standardized uptake value for detection of the immune response to the virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13550-015-0143-x) contains supplementary material, which is available to authorized users.",2015 Nov 16,"['Chefer, Svetlana', 'Thomasson, David', 'Seidel, Jurgen', 'Reba, Richard C.', 'Bohannon, J. Kyle', 'Lackemeyer, Mathew G.', 'Bartos, Chris', 'Sayre, Philip J.', 'Bollinger, Laura', 'Hensley, Lisa E.', 'Jahrling, Peter B.', 'Johnson, Reed F.']",EJNMMI Res,,,True
0e803f9a98199d4c1e322f933e9943db653460be,PMC,Development of reverse-transcription loop-mediated isothermal amplification assay for rapid detection and differentiation of dengue virus serotypes 1–4,http://dx.doi.org/10.1186/s12866-015-0595-1,PMC4647581,26572227,CC BY,"BACKGROUND: Dengue virus (DENV), the most widely prevalent arbovirus, continues to be a threat to human health in the tropics and subtropics. Early and rapid detection of DENV infection during the acute phase of illness is crucial for proper clinical patient management and preventing the spread of infection. The aim of the current study was to develop a specific, sensitive, and robust reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay for detection and differentiation of DENV1-4 serotypes. RESULTS: The method detection primers, which were designed to target the different DENV serotypes, were identified by inspection of multiple sequence alignments of the non-structural protein (NS) 2A of DENV1, NS4B of DENV2, NS4A of DENV3 and the 3′ untranslated region of the NS protein of DENV4. No cross-reactions of the four serotypes were observed during the tests. The detection limits of the DENV1-4-specific RT-LAMP assays were approximately 10-copy templates per reaction. The RT-LAMP assays were ten-fold more sensitive than RT-PCR or real-time PCR. The diagnostic rate was 100 % for clinical strains of DENV, and 98.9 % of the DENV-infected patients whose samples were tested were detected by RT-LAMP. Importantly, no false-positives were detected with the new equipment and methodology that was used to avoid aerosol contamination of the samples. CONCLUSION: The RT-LAMP method used in our study is specific, sensitive, and suitable for further investigation as a useful alternative to the current methods used for clinical diagnosis of DENV1-4, especially in hospitals and laboratories that lack sophisticated diagnostic systems.",2015 Nov 14,"['Hu, Sheng-feng', 'Li, Miao', 'Zhong, Lan-lan', 'Lu, Shi-miao', 'Liu, Ze-xia', 'Pu, Jie-ying', 'Wen, Jin-sheng', 'Huang, Xi']",BMC Microbiol,,,True
ae8c759fe82750edd66adb5e87e2ee44cb73c419,PMC,Polyethylene glycol-mediated fusion of herpes simplex type 1 virions with the plasma membrane of cells that support endocytic entry,http://dx.doi.org/10.1186/s12985-015-0423-0,PMC4647588,26573723,CC BY,"BACKGROUND: Mouse B78 cells and Chinese hamster ovary (CHO) cells are important to the study of HSV-1 entry because both are resistant to infection at the level of viral entry. When provided with a gD-receptor such as nectin-1, these cells support HSV-1 entry by an endocytosis pathway. Treating some viruses bound to cells with the fusogen polyethylene glycol (PEG) mediates viral fusion with the cell surface but is insufficient to rescue viral entry. It is unclear whether PEG-mediated fusion of HSV with the plasma membrane of B78 or CHO cells results in successful entry and infection. FINDINGS: Treating HSV-1 bound to B78 or CHO cells with PEG allowed viral entry as measured by virus-induced beta-galactosidase activity. Based on the mechanism of PEG action, we propose that entry likely proceeds by direct fusion of HSV particles with the plasma membrane. Under the conditions tested, PEG-mediated infection of CHO cells progressed to the level of HSV late gene expression, while B78 cells supported HSV DNA replication. We tested whether proteolysis or acidification of cell-bound virions could trigger HSV fusion with the plasma membrane. Under the conditions tested, mildly acidic pH of 5–6 or the protease trypsin were not capable of triggering HSV-1 fusion as compared to PEG-treated cell-bound virions. CONCLUSIONS: B78 cells and CHO cells, which typically endocytose HSV prior to viral penetration, are capable of supporting HSV-1 entry via direct penetration. HSV capsids delivered directly to the cytosol at the periphery of these cells complete the entry process. B78 and CHO cells may be utilized to screen for factors that trigger entry as a consequence of fusion of virions with the cell surface, and PEG treatment can provide a necessary control.",2015 Nov 16,"['Walker, Erik B.', 'Pritchard, Suzanne M.', 'Cunha, Cristina W.', 'Aguilar, Hector C.', 'Nicola, Anthony V.']",Virol J,,,True
f80fdfc8ac74900c266137137e0a1cd6b6e12b02,PMC,Differential proteomic analysis of virus-enriched fractions obtained from plasma pools of patients with dengue fever or severe dengue,http://dx.doi.org/10.1186/s12879-015-1271-7,PMC4647599,26572220,CC BY,"BACKGROUND: Dengue is the most widespread mosquito-borne viral disease of public health concern. In some patients, endothelial cell and platelet dysfunction lead to life-threatening hemorrhagic dengue fever or dengue shock syndrome. Prognostication of disease severity is urgently required to improve patient management. The pathogenesis of severe dengue has not been fully elucidated, and the role of host proteins associated with viral particles has received little exploration. METHODS: The proteomes of virion-enriched fractions purified from plasma pools of patients with dengue fever or severe dengue were compared. Virions were purified by ultracentrifugation combined with a water-insoluble polyelectrolyte-based technique. Following in-gel hydrolysis, peptides were analyzed by nano-liquid chromatography coupled to ion trap mass spectrometry and identified using data libraries. RESULTS: Both dengue fever and severe dengue viral-enriched fractions contained identifiable viral envelope proteins and host cellular proteins. Canonical pathway analysis revealed the identified host proteins are mainly involved in the coagulation cascade, complement pathway or acute phase response signaling pathway. Some host proteins were over- or under-represented in plasma from patients with severe dengue compared to patients with dengue fever. ELISAs were used to validate differential expression of a selection of identified host proteins in individual plasma samples of patients with dengue fever compared to patients with severe dengue. Among 22 host proteins tested, two could differentiate between dengue fever and severe dengue in two independent cohorts (olfactomedin-4: area under the curve (AUC), 0.958; and platelet factor-4: AUC, 0.836). CONCLUSION: A novel technique of virion-enrichment from plasma has allowed to identify two host proteins that have prognostic value for classifying patients with acute dengue who are more likely to develop a severe dengue. The impact of these host proteins on pathogenicity and disease outcome are discussed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1271-7) contains supplementary material, which is available to authorized users.",2015 Nov 14,"['Fragnoud, Romain', 'Flamand, Marie', 'Reynier, Frederic', 'Buchy, Philippe', 'Duong, Vasna', 'Pachot, Alexandre', 'Paranhos-Baccala, Glaucia', 'Bedin, Frederic']",BMC Infect Dis,,,False
c0bec3dd80af76e0f60020b72ab8f6e1f14354fb,PMC,Differential proteomic analysis of virus-enriched fractions obtained from plasma pools of patients with dengue fever or severe dengue,http://dx.doi.org/10.1186/s12879-015-1271-7,PMC4647599,26572220,CC BY,"BACKGROUND: Dengue is the most widespread mosquito-borne viral disease of public health concern. In some patients, endothelial cell and platelet dysfunction lead to life-threatening hemorrhagic dengue fever or dengue shock syndrome. Prognostication of disease severity is urgently required to improve patient management. The pathogenesis of severe dengue has not been fully elucidated, and the role of host proteins associated with viral particles has received little exploration. METHODS: The proteomes of virion-enriched fractions purified from plasma pools of patients with dengue fever or severe dengue were compared. Virions were purified by ultracentrifugation combined with a water-insoluble polyelectrolyte-based technique. Following in-gel hydrolysis, peptides were analyzed by nano-liquid chromatography coupled to ion trap mass spectrometry and identified using data libraries. RESULTS: Both dengue fever and severe dengue viral-enriched fractions contained identifiable viral envelope proteins and host cellular proteins. Canonical pathway analysis revealed the identified host proteins are mainly involved in the coagulation cascade, complement pathway or acute phase response signaling pathway. Some host proteins were over- or under-represented in plasma from patients with severe dengue compared to patients with dengue fever. ELISAs were used to validate differential expression of a selection of identified host proteins in individual plasma samples of patients with dengue fever compared to patients with severe dengue. Among 22 host proteins tested, two could differentiate between dengue fever and severe dengue in two independent cohorts (olfactomedin-4: area under the curve (AUC), 0.958; and platelet factor-4: AUC, 0.836). CONCLUSION: A novel technique of virion-enrichment from plasma has allowed to identify two host proteins that have prognostic value for classifying patients with acute dengue who are more likely to develop a severe dengue. The impact of these host proteins on pathogenicity and disease outcome are discussed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1271-7) contains supplementary material, which is available to authorized users.",2015 Nov 14,"['Fragnoud, Romain', 'Flamand, Marie', 'Reynier, Frederic', 'Buchy, Philippe', 'Duong, Vasna', 'Pachot, Alexandre', 'Paranhos-Baccala, Glaucia', 'Bedin, Frederic']",BMC Infect Dis,,,True
6dab259f3cac146d0cadf07d4085a8ecc4069bed,PMC,Tracking social contact networks with online respondent-driven detection: who recruits whom?,http://dx.doi.org/10.1186/s12879-015-1250-z,PMC4647802,26573658,CC BY,"BACKGROUND: Transmission of respiratory pathogens in a population depends on the contact network patterns of individuals. To accurately understand and explain epidemic behaviour information on contact networks is required, but only limited empirical data is available. Online respondent-driven detection can provide relevant epidemiological data on numbers of contact persons and dynamics of contacts between pairs of individuals. We aimed to analyse contact networks with respect to sociodemographic and geographical characteristics, vaccine-induced immunity and self-reported symptoms. METHODS: In 2014, volunteers from two large participatory surveillance panels in the Netherlands and Belgium were invited for a survey. Participants were asked to record numbers of contacts at different locations and self-reported influenza-like-illness symptoms, and to invite 4 individuals they had met face to face in the preceding 2 weeks. We calculated correlations between linked individuals to investigate mixing patterns. RESULTS: In total 1560 individuals completed the survey who reported in total 30591 contact persons; 488 recruiter-recruit pairs were analysed. Recruitment was assortative by age, education, household size, influenza vaccination status and sentiments, indicating that participants tended to recruit contact persons similar to themselves. We also found assortative recruitment by symptoms, reaffirming our objective of sampling contact persons whom a participant may infect or by whom a participant may get infected in case of an outbreak. Recruitment was random by sex and numbers of contact persons. Relationships between pairs were influenced by the spatial distribution of peer recruitment. CONCLUSIONS: Although complex mechanisms influence online peer recruitment, the observed statistical relationships reflected the observed contact network patterns in the general population relevant for the transmission of respiratory pathogens. This provides useful and innovative input for predictive epidemic models relying on network information. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1250-z) contains supplementary material, which is available to authorized users.",2015 Nov 14,"['Stein, Mart L.', 'van der Heijden, Peter G. M.', 'Buskens, Vincent', 'van Steenbergen, Jim E.', 'Bengtsson, Linus', 'Koppeschaar, Carl E.', 'Thorson, Anna', 'Kretzschmar, Mirjam E. E.']",BMC Infect Dis,,,True
6c04f5f55db4cef127e6799e220f5cb86b9ffa18,PMC,Tracking social contact networks with online respondent-driven detection: who recruits whom?,http://dx.doi.org/10.1186/s12879-015-1250-z,PMC4647802,26573658,CC BY,"BACKGROUND: Transmission of respiratory pathogens in a population depends on the contact network patterns of individuals. To accurately understand and explain epidemic behaviour information on contact networks is required, but only limited empirical data is available. Online respondent-driven detection can provide relevant epidemiological data on numbers of contact persons and dynamics of contacts between pairs of individuals. We aimed to analyse contact networks with respect to sociodemographic and geographical characteristics, vaccine-induced immunity and self-reported symptoms. METHODS: In 2014, volunteers from two large participatory surveillance panels in the Netherlands and Belgium were invited for a survey. Participants were asked to record numbers of contacts at different locations and self-reported influenza-like-illness symptoms, and to invite 4 individuals they had met face to face in the preceding 2 weeks. We calculated correlations between linked individuals to investigate mixing patterns. RESULTS: In total 1560 individuals completed the survey who reported in total 30591 contact persons; 488 recruiter-recruit pairs were analysed. Recruitment was assortative by age, education, household size, influenza vaccination status and sentiments, indicating that participants tended to recruit contact persons similar to themselves. We also found assortative recruitment by symptoms, reaffirming our objective of sampling contact persons whom a participant may infect or by whom a participant may get infected in case of an outbreak. Recruitment was random by sex and numbers of contact persons. Relationships between pairs were influenced by the spatial distribution of peer recruitment. CONCLUSIONS: Although complex mechanisms influence online peer recruitment, the observed statistical relationships reflected the observed contact network patterns in the general population relevant for the transmission of respiratory pathogens. This provides useful and innovative input for predictive epidemic models relying on network information. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1250-z) contains supplementary material, which is available to authorized users.",2015 Nov 14,"['Stein, Mart L.', 'van der Heijden, Peter G. M.', 'Buskens, Vincent', 'van Steenbergen, Jim E.', 'Bengtsson, Linus', 'Koppeschaar, Carl E.', 'Thorson, Anna', 'Kretzschmar, Mirjam E. E.']",BMC Infect Dis,,,True
e666325d40e18c90c35e6a6eb9b5723a28cc15ad,PMC,Respiratory consequences of N95-type Mask usage in pregnant healthcare workers—a controlled clinical study,http://dx.doi.org/10.1186/s13756-015-0086-z,PMC4647822,26579222,CC BY,"BACKGROUND: Outbreaks of emerging infectious diseases have led to guidelines recommending the routine use of N95 respirators for healthcare workers, many of whom are women of childbearing age. The respiratory effects of prolonged respirator use on pregnant women are unclear although there has been no definite evidence of harm from past use. METHODS: We conducted a two-phase controlled clinical study on healthy pregnant women between 27 to 32 weeks gestation. In phase I, energy expenditure corresponding to the workload of routine nursing tasks was determined. In phase II, pulmonary function of 20 subjects was measured whilst at rest and exercising to the predetermined workload while breathing ambient air first, then breathing through N95-mask materials. RESULTS: Exercising at 3 MET while breathing through N95-mask materials reduced mean tidal volume (TV) by 23.0 % (95 % CI −33.5 % to −10.5 %, p < 0.001) and lowered minute ventilation (VE) by 25.8 % (95 % CI −34.2 % to −15.8 %, p < 0.001), with no significant change in breathing frequency compared to breathing ambient air. Volumes of oxygen consumption (VO(2)) and carbon dioxide expired (VCO(2)) were also significantly reduced; VO(2) by 13.8 % (95 % CI −24.2 % to −3 %, p = 0.013) and VCO(2) by 17.7 %, (95 % CI −28.1 % to −8.6 %, p = 0.001). Although no changes in the inspired oxygen and carbon dioxide concentrations were demonstrated, breathing through N95-mask materials during low intensity work (3 MET) reduced expired oxygen concentration by 3.2 % (95 % CI: −4.1 % to −2.2 %, p < 0.001), and increased expired carbon dioxide by 8.9 % (95 % CI: 6.9 % to 13.1 %; p <0.001) suggesting an increase in metabolism. There were however no changes in the maternal and fetal heart rates, finger-tip capillary lactate levels and oxygen saturation and rating of perceived exertion at the work intensity investigated. CONCLUSIONS: Breathing through N95 mask materials have been shown to impede gaseous exchange and impose an additional workload on the metabolic system of pregnant healthcare workers, and this needs to be taken into consideration in guidelines for respirator use. The benefits of using N95 mask to prevent serious emerging infectious diseases should be weighed against potential respiratory consequences associated with extended N95 respirator usage. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov, identifier NCT00265926.",2015 Nov 16,"['Tong, Pearl Shuang Ye', 'Kale, Anita Sugam', 'Ng, Kailyn', 'Loke, Amelia Peiwen', 'Choolani, Mahesh Arjandas', 'Lim, Chin Leong', 'Chan, Yiong Huak', 'Chong, Yap Seng', 'Tambyah, Paul Anantharajah', 'Yong, Eu-Leong']",Antimicrob Resist Infect Control,,,True
197679559a6aa8d3f30bde60d9387f1f9f975c0a,PMC,Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia,http://dx.doi.org/10.1371/journal.pone.0143152,PMC4648489,26576054,CC BY,"OBJECTIVES: To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. DESIGN: A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. SETTING: Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. PARTICIPANTS: Ninety-one adult patients with acute respiratory infection (55% were female). MEASUREMENTS: Viral identification, intensive care unit admission, hospital stay, and mortality. RESULTS: Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. CONCLUSIONS: The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality.",2015 Nov 17,"['Remolina, Yuly Andrea', 'Ulloa, María Mercedes', 'Vargas, Hernán', 'Díaz, Liliana', 'Gómez, Sandra Liliana', 'Saavedra, Alfredo', 'Sánchez, Edgar', 'Cortés, Jorge Alberto']",PLoS One,,,True
5de6f9a65ba8f1857af0057539ff471a4427a157,PMC,Functional variants regulating LGALS1 (Galectin 1) expression affect human susceptibility to influenza A(H7N9),http://dx.doi.org/10.1038/srep08517,PMC4649671,25687228,CC BY,"The fatality of avian influenza A(H7N9) infection in humans was over 30%. To identify human genetic susceptibility to A(H7N9) infection, we performed a genome-wide association study (GWAS) involving 102 A(H7N9) patients and 106 heavily-exposed healthy poultry workers, a sample size critically restricted by the small number of human A(H7N9) cases. To tackle the stringent significance cutoff of GWAS, we utilized an artificial imputation program SnipSnip to improve the association signals. In single-SNP analysis, one of the top SNPs was rs13057866 of LGALS1. The artificial imputation (AI) identified three non-genotyped causal variants, which can be represented by three anchor/partner SNP pairs rs13057866/rs9622682 (AI P = 1.81 × 10(−7)), rs4820294/rs2899292 (2.13 × 10(−7)) and rs62236673/rs2899292 (4.25 × 10(−7)) respectively. Haplotype analysis of rs4820294 and rs2899292 could simulate the signal of a causal variant. The rs4820294/rs2899292 haplotype GG, in association with protection from A(H7N9) infection (OR = 0.26, P = 5.92 × 10(−7)) correlated to significantly higher levels of LGALS1 mRNA (P = 0.050) and protein expression (P = 0.025) in lymphoblast cell lines. Additionally, rs4820294 was mapped as an eQTL in human primary monocytes and lung tissues. In conclusion, functional variants of LGALS1 causing the expression variations are contributable to the differential susceptibility to influenza A(H7N9).",2015 Feb 17,"['Chen, Yu', 'Zhou, Jie', 'Cheng, Zhongshan', 'Yang, Shigui', 'Chu, Hin', 'Fan, Yanhui', 'Li, Cun', 'Wong, Bosco Ho-Yin', 'Zheng, Shufa', 'Zhu, Yixin', 'Yu, Fei', 'Wang, Yiyin', 'Liu, Xiaoli', 'Gao, Hainv', 'Yu, Liang', 'Tang, Linglin', 'Cui, Dawei', 'Hao, Ke', 'Bossé, Yohan', 'Obeidat, Ma′en', 'Brandsma, Corry-Anke', 'Song, You-Qiang', 'To, Kelvin Kai-Wang', 'Sham, Pak Chung', 'Yuen, Kwok-Yung', 'Li, Lanjuan']",Sci Rep,,,True
b98f753cf246353e2ffff6822aeff4f2f3c5a7b5,PMC,Antiviral Phosphorodiamidate Morpholino Oligomers are Protective against Chikungunya Virus Infection on Cell-based and Murine Models,http://dx.doi.org/10.1038/srep12727,PMC4649900,26224141,CC BY,"Chikungunya virus (CHIKV) infection in human is associated with debilitating and persistent arthralgia and arthritis. Currently, there is no specific vaccine or effective antiviral available. Anti-CHIKV Phosphorodiamidate Morpholino Oligomer (CPMO) was evaluated for its antiviral efficacy and cytotoxcity in human cells and neonate murine model. Two CPMOs were designed to block translation initiation of a highly conserved sequence in CHIKV non-structural and structural polyprotein, respectively. Pre-treatment of HeLa cells with CPMO1 signficantly suppressed CHIKV titre, CHIKV E2 protein expression and prevented CHIKV-induced CPE. CPMO1 activity was also CHIKV-specific as shown by the lack of cross-reactivity against SINV or DENV replication. When administered prophylactically in neonate mice, 15 μg/g CPMO1v conferred 100% survival against CHIKV disease. In parallel, these mice demonstrated significant reduction in viremia and viral load in various tissues. Immunohistological examination of skeletal muscles and liver of CPMO1v-treated mice also showed healthy tissue morphology, in contrast to evident manifestation of CHIKV pathogenesis in PBS- or scrambled sCPMO1v-treated groups. Taken together, our findings highlight for the first time that CPMO1v has strong protective effect against CHIKV infection. This warrants future development of morpholino as an alternative antiviral agent to address CHIKV infection in clinical applications.",2015 Jul 30,"['Lam, Shirley', 'Chen, Huixin', 'Chen, Caiyun Karen', 'Min, Nyo', 'Chu, Justin Jang Hann']",Sci Rep,,,True
7c3be5c1501f68e5305325f4acac221632ccb290,PMC,Impact of antibacterials on subsequent resistance and clinical outcomes in adult patients with viral pneumonia: an opportunity for stewardship,http://dx.doi.org/10.1186/s13054-015-1120-5,PMC4650137,26577540,CC BY,"INTRODUCTION: Respiratory viruses are increasingly recognized as significant etiologies of pneumonia among hospitalized patients. Advanced technologies using multiplex molecular assays and polymerase-chain reaction increase the ability to identify viral pathogens and may ultimately impact antibacterial use. METHOD: This was a single-center retrospective cohort study to evaluate the impact of antibacterials in viral pneumonia on clinical outcomes and subsequent multidrug-resistant organism (MDRO) infections/colonization. Patients admitted from March 2013 to November 2014 with positive respiratory viral panels (RVP) and radiographic findings of pneumonia were included. Patients transferred from an outside hospital or not still hospitalized 72 hours after the RVP report date were excluded. Patients were categorized based on exposure to systemic antibacterials: less than 3 days representing short-course therapy and 3 to 10 days being long-course therapy. RESULTS: A total of 174 patients (long-course, n = 67; short-course, n = 28; mixed bacterial-viral infection, n = 79) were included with most being immunocompromised (56.3 %) with active malignancy the primary etiology (69.4 %). Rhinovirus/Enterovirus (23 %), Influenza (19 %), and Parainfluenza (15.5 %) were the viruses most commonly identified. A total of 13 different systemic antibacterials were used as empiric therapy in the 95 patients with pure viral infection for a total of 466 days-of-therapy. Vancomycin (50.7 %), cefepime (40.3 %), azithromycin (40.3 %), meropenem (23.9 %), and linezolid (20.9 %) were most frequently used. In-hospital mortality did not differ between patients with viral pneumonia in the short-course and long-course groups. Subsequent infection/colonization with a MDRO was more frequent in the long-course group compared to the short-course group (53.2 vs 21.1 %; P = 0.027). CONCLUSION: This study found that long-course antibacterial use in the setting of viral pneumonia had no impact on clinical outcomes but increased the incidence of subsequent MDRO infection/colonization.",2015 Nov 18,"['Crotty, Matthew P.', 'Meyers, Shelby', 'Hampton, Nicholas', 'Bledsoe, Stephanie', 'Ritchie, David J.', 'Buller, Richard S.', 'Storch, Gregory A.', 'Kollef, Marin H.', 'Micek, Scott T.']",Crit Care,,,True
0f537e86e84193917fff3e7152e74148d158c5be,PMC,Actinobacillus pleuropneumoniae induces SJPL cell cycle arrest in G2/M-phase and inhibits porcine reproductive and respiratory syndrome virus replication,http://dx.doi.org/10.1186/s12985-015-0404-3,PMC4650394,26577697,CC BY,"BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in the swine industry and causes important economic losses. No effective antiviral drugs against it are commercially available. We recently reported that the culture supernatant of Actinobacillus pleuropneumoniae, the porcine pleuropneumonia causative agent, has an antiviral activity in vitro against PRRSV in SJPL cells. Objectives of this study were (i) to identify the mechanism behind the antiviral activity displayed by A. pleuropneumoniae and (ii) to characterize the active molecules present in the bacterial culture supernatant. METHODS: Antibody microarray analysis was used in order to point out cellular pathways modulated by the A. pleuropneumoniae supernatant. Subsequent, flow cytometry analysis and cell cycle inhibitors were used to confirm antibody microarray data and to link them to the antiviral activity of the A. pleuropneumoniae supernatant. Finally, A. pleuropneumoniae supernatant characterization was partially achieved using mass spectrometry. RESULTS: Using antibody microarray, we observed modulations in G2/M-phase cell cycle regulation pathway when SJPL cells were treated with A. pleuropneumoniae culture supernatant. These modulations were confirmed by a cell cycle arrest at the G2/M-phase when cells were treated with the A. pleuropneumoniae culture supernatant. Furthermore, two G2/M-phase cell cycle inhibitors demonstrated the ability to inhibit PRRSV infection, indicating a potential key role for PRRSV infection. Finally, mass spectrometry lead to identify two molecules (m/z 515.2 and m/z 663.6) present only in the culture supernatant. CONCLUSIONS: We demonstrated for the first time that A. pleuropneumoniae is able to disrupt SJPL cell cycle resulting in inhibitory activity against PRRSV. Furthermore, two putative molecules were identified from the culture supernatant. This study highlighted the cell cycle importance for PRRSV and will allow the development of new prophylactic or therapeutic approaches against PRRSV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0404-3) contains supplementary material, which is available to authorized users.",2015 Nov 14,"['Ferreira Barbosa, Jérémy A.', 'Labrie, Josée', 'Beaudry, Francis', 'Gagnon, Carl A.', 'Jacques, Mario']",Virol J,,,True
c7b980605c4ba138f35378e5f56b95e677cc87c5,PMC,Ubiquitin-specific Protease 15 Negatively Regulates Virus-induced Type I Interferon Signaling via Catalytically-dependent and -independent Mechanisms,http://dx.doi.org/10.1038/srep11220,PMC4650652,26061460,CC BY,"Viral infection triggers a series of signaling cascades, which converge to activate the transcription factors nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3), thereby inducing the transcription of type I interferons (IFNs). Although not fully characterized, these innate antiviral responses are fine-tuned by dynamic ubiquitination and deubiquitination processes. In this study, we report ubiquitin-specific protease (USP) 15 is involved in regulation of the retinoic acid-inducible gene I (RIG-I)-dependent type I IFN induction pathway. Knockdown of endogenous USP15 augmented cellular antiviral responses. Overexpression of USP15 inhibited the transcription of IFN-β. Further analyses identified histidine 862 as a critical residue for USP15’s catalytic activity. Interestingly, USP15 specifically removed lysine 63-linked polyubiquitin chains from RIG-I among the essential components in RIG-I-like receptor-dependent pathway. In addition, we demonstrated that in contrast to USP15 de-ubiquitinating (DUB) activity, USP15-mediated inhibition of IFN signaling was not abolished by mutations eliminating the catalytic activity, indicating that a fraction of USP15-mediated IFN antagonism was independent of the DUB activity. Catalytically inactive USP15 mutants, as did the wild-type protein, disrupted virus-induced interaction of RIG-I and IFN-β promoter stimulator 1. Taken together, our data demonstrate that USP15 acts as a negative regulator of RIG-I signaling via DUB-dependent and independent mechanisms.",2015 Jun 10,"['Zhang, Huan', 'Wang, Dang', 'Zhong, Huijuan', 'Luo, Rui', 'Shang, Min', 'Liu, Dezhi', 'Chen, Huanchun', 'Fang, Liurong', 'Xiao, Shaobo']",Sci Rep,,,True
0f27c25599e793f5628c7d8519eeaabbf7887ca2,PMC,Ubiquitin-specific Protease 15 Negatively Regulates Virus-induced Type I Interferon Signaling via Catalytically-dependent and -independent Mechanisms,http://dx.doi.org/10.1038/srep11220,PMC4650652,26061460,CC BY,"Viral infection triggers a series of signaling cascades, which converge to activate the transcription factors nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3), thereby inducing the transcription of type I interferons (IFNs). Although not fully characterized, these innate antiviral responses are fine-tuned by dynamic ubiquitination and deubiquitination processes. In this study, we report ubiquitin-specific protease (USP) 15 is involved in regulation of the retinoic acid-inducible gene I (RIG-I)-dependent type I IFN induction pathway. Knockdown of endogenous USP15 augmented cellular antiviral responses. Overexpression of USP15 inhibited the transcription of IFN-β. Further analyses identified histidine 862 as a critical residue for USP15’s catalytic activity. Interestingly, USP15 specifically removed lysine 63-linked polyubiquitin chains from RIG-I among the essential components in RIG-I-like receptor-dependent pathway. In addition, we demonstrated that in contrast to USP15 de-ubiquitinating (DUB) activity, USP15-mediated inhibition of IFN signaling was not abolished by mutations eliminating the catalytic activity, indicating that a fraction of USP15-mediated IFN antagonism was independent of the DUB activity. Catalytically inactive USP15 mutants, as did the wild-type protein, disrupted virus-induced interaction of RIG-I and IFN-β promoter stimulator 1. Taken together, our data demonstrate that USP15 acts as a negative regulator of RIG-I signaling via DUB-dependent and independent mechanisms.",2015 Jun 10,"['Zhang, Huan', 'Wang, Dang', 'Zhong, Huijuan', 'Luo, Rui', 'Shang, Min', 'Liu, Dezhi', 'Chen, Huanchun', 'Fang, Liurong', 'Xiao, Shaobo']",Sci Rep,,,False
19ddf65d65d5e172ac3ceda4662b68769633dbe6,PMC,Dynamics of Multi-stage Infections on Networks,http://dx.doi.org/10.1007/s11538-015-0109-1,PMC4651987,26403422,CC BY,"This paper investigates the dynamics of infectious diseases with a non-exponentially distributed infectious period. This is achieved by considering a multi-stage infection model on networks. Using pairwise approximation with a standard closure, a number of important characteristics of disease dynamics are derived analytically, including the final size of an epidemic and a threshold for epidemic outbreaks, and it is shown how these quantities depend on disease characteristics, as well as the number of disease stages. Stochastic simulations of dynamics on networks are performed and compared to output of pairwise models for several realistic examples of infectious diseases to illustrate the role played by the number of stages in the disease dynamics. These results show that a higher number of disease stages results in faster epidemic outbreaks with a higher peak prevalence and a larger final size of the epidemic. The agreement between the pairwise and simulation models is excellent in the cases we consider.",2015 Sep 24,"['Sherborne, N.', 'Blyuss, K. B.', 'Kiss, I. Z.']",Bull Math Biol,,,True
1edab5890fbff22ad353739d3d1e80a86d482820,PMC,"Handwashing with soap and national handwashing projects in Korea: focus on the National Handwashing Survey, 2006-2014",http://dx.doi.org/10.4178/epih/e2015039,PMC4652062,26725224,CC BY,"OBJECTIVES: Handwashing is the most fundamental way to prevent the spread of infectious diseases. Correct handwashing can prevent 50 to 70% of water-infections and foodborne-infections. We report the results of a fact-finding study on general handwashing attitude and practice in the Republic of Korea by analyzing habits and awareness among adults and students (grades 4 to 12) based on the 2006 to 2014 National Handwashing Surveys and observational surveys. METHODS: The awareness survey was performed by telephone interviews with adults and students in 16 municipalities and provinces sampled by quota for region, sex and age. The observational survey was performed in subway, railway, and other public restrooms in seven municipalities selected through systematic sampling. RESULTS: Adults and students washed their hands with soap/sanitizer an average of 6.6 and 5.2 times daily, respectively, in 2014, an increase and decrease compared to 2006 (4.8) and 2013 (6.8). Their average daily handwashing frequency in 2014, 9.8 and 8.3, was higher than in 2006 (7.6), but lower than in 2013 (10.3).The percentage of participants handwashing with soap after using the restroom (29.5%) has been increasing since 2009, but remain slower than in other countries (42% to 49%). The percentages of participants handwashing with water in 2014, 2013, and 2011 were 57.5%, 72.6%, and 71.4%, respectively. CONCLUSIONS: Handwashing with soap is an important national public health issue, and national projects promoting it should be given high priority. Research support is necessary to provide scientific evidence of the importance of handwashing with soap and to develop and implement evidence-based policies.",2015 Aug 31,"['Lee, Moo-Sik', 'Hong, Su Jin', 'Kim, Young-Taek']",Epidemiol Health,,,True
1505b1491459e5a9d560f06da7c48ae278bc48bc,PMC,"Handwashing with soap and national handwashing projects in Korea: focus on the National Handwashing Survey, 2006-2014",http://dx.doi.org/10.4178/epih/e2015039,PMC4652062,26725224,CC BY,"OBJECTIVES: Handwashing is the most fundamental way to prevent the spread of infectious diseases. Correct handwashing can prevent 50 to 70% of water-infections and foodborne-infections. We report the results of a fact-finding study on general handwashing attitude and practice in the Republic of Korea by analyzing habits and awareness among adults and students (grades 4 to 12) based on the 2006 to 2014 National Handwashing Surveys and observational surveys. METHODS: The awareness survey was performed by telephone interviews with adults and students in 16 municipalities and provinces sampled by quota for region, sex and age. The observational survey was performed in subway, railway, and other public restrooms in seven municipalities selected through systematic sampling. RESULTS: Adults and students washed their hands with soap/sanitizer an average of 6.6 and 5.2 times daily, respectively, in 2014, an increase and decrease compared to 2006 (4.8) and 2013 (6.8). Their average daily handwashing frequency in 2014, 9.8 and 8.3, was higher than in 2006 (7.6), but lower than in 2013 (10.3).The percentage of participants handwashing with soap after using the restroom (29.5%) has been increasing since 2009, but remain slower than in other countries (42% to 49%). The percentages of participants handwashing with water in 2014, 2013, and 2011 were 57.5%, 72.6%, and 71.4%, respectively. CONCLUSIONS: Handwashing with soap is an important national public health issue, and national projects promoting it should be given high priority. Research support is necessary to provide scientific evidence of the importance of handwashing with soap and to develop and implement evidence-based policies.",2015 Aug 31,"['Lee, Moo-Sik', 'Hong, Su Jin', 'Kim, Young-Taek']",Epidemiol Health,,,False
55b3d85d69f463bf877361addcaba605014f2231,PMC,Epidemiologic features of the first MERS outbreak in Korea: focus on Pyeongtaek St. Mary’s Hospital,http://dx.doi.org/10.4178/epih/e2015041,PMC4652064,26725225,CC BY,"OBJECTIVES: This study investigated the epidemiologic features of the confirmed cases of Middle East Respiratory Syndrome (MERS) in Pyeongtaek St. Mary’s Hospital, where the outbreak first began, in order to identify lessons relevant for the prevention and control of future outbreaks. METHODS: The patients’ clinical symptoms and test results were collected from their medical records. The caregivers of patients were identified by phone calls. RESULTS: After patient zero (case #1) was admitted to Pyeongtaek St. Mary’s Hospital (May 15-May 17), an outbreak occurred, with 36 cases between May 18 and June 4, 2015. Six patients died (fatality rate, 16.7%). Twenty-six cases occurred in the first-generation, and 10 in the second-generation. The median incubation period was five days, while the median period from symptom onset to death was 12.5 days. While the total attack rate was 3.9%, the attack rate among inpatients was 7.6%, and the inpatients on the eighth floor, where patient zero was hospitalized, had an 18.6% attack rate. In contrast, caregivers and medical staff showed attack rates of 3.3% and 1.1%, respectively. CONCLUSIONS: The attack rates were higher than those of the previous outbreaks in other countries. The outbreak spread beyond Pyeongtaek St. Mary’s Hospital when four of the patients were moved to other hospitals without appropriate quarantine. The best method of preventing future outbreaks is to overcome the vulnerabilities observed in this outbreak, such as ward crowding, patient migration without appropriate data sharing, and the lack of an initial broad quarantine.",2015 Sep 17,"['Kim, Kyung Min', 'Ki, Moran', 'Cho, Sung-il', 'Sung, Minki', 'Hong, Jin Kwan', 'Cheong, Hae-Kwan', 'Kim, Jong-Hun', 'Lee, Sang-Eun', 'Lee, Changhwan', 'Lee, Keon-Joo', 'Park, Yong-Shik', 'Kim, Seung Woo', 'Choi, Bo Youl']",Epidemiol Health,,,True
ed5d3f1db5936c2b86eb9ea46eab96a0b67a124e,PMC,Epidemiologic features of the first MERS outbreak in Korea: focus on Pyeongtaek St. Mary’s Hospital,http://dx.doi.org/10.4178/epih/e2015041,PMC4652064,26725225,CC BY,"OBJECTIVES: This study investigated the epidemiologic features of the confirmed cases of Middle East Respiratory Syndrome (MERS) in Pyeongtaek St. Mary’s Hospital, where the outbreak first began, in order to identify lessons relevant for the prevention and control of future outbreaks. METHODS: The patients’ clinical symptoms and test results were collected from their medical records. The caregivers of patients were identified by phone calls. RESULTS: After patient zero (case #1) was admitted to Pyeongtaek St. Mary’s Hospital (May 15-May 17), an outbreak occurred, with 36 cases between May 18 and June 4, 2015. Six patients died (fatality rate, 16.7%). Twenty-six cases occurred in the first-generation, and 10 in the second-generation. The median incubation period was five days, while the median period from symptom onset to death was 12.5 days. While the total attack rate was 3.9%, the attack rate among inpatients was 7.6%, and the inpatients on the eighth floor, where patient zero was hospitalized, had an 18.6% attack rate. In contrast, caregivers and medical staff showed attack rates of 3.3% and 1.1%, respectively. CONCLUSIONS: The attack rates were higher than those of the previous outbreaks in other countries. The outbreak spread beyond Pyeongtaek St. Mary’s Hospital when four of the patients were moved to other hospitals without appropriate quarantine. The best method of preventing future outbreaks is to overcome the vulnerabilities observed in this outbreak, such as ward crowding, patient migration without appropriate data sharing, and the lack of an initial broad quarantine.",2015 Sep 17,"['Kim, Kyung Min', 'Ki, Moran', 'Cho, Sung-il', 'Sung, Minki', 'Hong, Jin Kwan', 'Cheong, Hae-Kwan', 'Kim, Jong-Hun', 'Lee, Sang-Eun', 'Lee, Changhwan', 'Lee, Keon-Joo', 'Park, Yong-Shik', 'Kim, Seung Woo', 'Choi, Bo Youl']",Epidemiol Health,,,True
8923bae528dc7e9ed10fbb6e823707dd1018be9d,PMC,Reference gene selection for normalization of RT-qPCR gene expression data from Actinidia deliciosa leaves infected with Pseudomonas syringae pv. actinidiae,http://dx.doi.org/10.1038/srep16961,PMC4652207,26581656,CC BY,"Normalization of data, by choosing the appropriate reference genes (RGs), is fundamental for obtaining reliable results in reverse transcription-quantitative PCR (RT-qPCR). In this study, we assessed Actinidia deliciosa leaves inoculated with two doses of Pseudomonas syringae pv. actinidiae during a period of 13 days for the expression profile of nine candidate RGs. Their expression stability was calculated using four algorithms: geNorm, NormFinder, BestKeeper and the deltaCt method. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and protein phosphatase 2A (PP2A) were the most stable genes, while β-tubulin and 7s-globulin were the less stable. Expression analysis of three target genes, chosen for RGs validation, encoding the reactive oxygen species scavenging enzymes ascorbate peroxidase (APX), superoxide dismutase (SOD) and catalase (CAT) indicated that a combination of stable RGs, such as GAPDH and PP2A, can lead to an accurate quantification of the expression levels of such target genes. The APX level varied during the experiment time course and according to the inoculum doses, whereas both SOD and CAT resulted down-regulated during the first four days, and up-regulated afterwards, irrespective of inoculum dose. These results can be useful for better elucidating the molecular interaction in the A. deliciosa/P. s. pv. actinidiae pathosystem and for RGs selection in bacteria-plant pathosystems.",2015 Nov 19,"['Petriccione, Milena', 'Mastrobuoni, Francesco', 'Zampella, Luigi', 'Scortichini, Marco']",Sci Rep,,,True
0e5168af60cc8a258ea92c0a87f4ae16f235c7c9,PMC,NK cells in asthma exacerbation,,PMC4652962,26296976,CC BY,,2015 Jul 8,"['Lunding, Lars', 'Wegmann, Michael']",Oncotarget,,,False
28fbe1da18bb4a2e0f8a42013e14794b6f3038f4,PMC,"Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol",http://dx.doi.org/10.1186/s40064-015-1490-9,PMC4653124,26618098,CC BY,"As of September 30, 2015, a total of 1589 laboratory-confirmed cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization (WHO). At present there is no effective specific therapy against MERS-CoV. The use of convalescent plasma (CP) has been suggested as a potential therapy based on existing evidence from other viral infections. We aim to study the feasibility of CP therapy as well as its safety and clinical and laboratory effects in critically ill patients with MERS-CoV infection. We will also examine the pharmacokinetics of the MERS-CoV antibody response and viral load over the course of MERS-CoV infection. This study will inform a future randomized controlled trial that will examine the efficacy of CP therapy for MERS-CoV infection. In the CP collection phase, potential donors will be tested by the enzyme linked immunosorbent assay (ELISA) and the indirect fluorescent antibody (IFA) techniques for the presence of anti-MERS-CoV antibodies. Subjects with anti-MERS-CoV IFA titer of ≥1:160 and no clinical or laboratory evidence of MERS-CoV infection will be screened for eligibility for plasma donation according to standard donation criteria. In the CP therapy phase, 20 consecutive critically ill patients admitted to intensive care unit with laboratory-confirmed MERS-CoV infection will be enrolled and each will receive 2 units of CP. Post enrollment, patients will be followed for clinical and laboratory outcomes that include anti-MERS-CoV antibodies and viral load. This protocol was developed collaboratively by King Abdullah International Medical Research Center (KAIMRC), Gulf Cooperation Council (GCC) Infection Control Center Group and the World Health Organization—International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO) MERS-CoV Working Group. It was approved in June 2014 by the Ministry of the National Guard Health Affairs Institutional Review Board (IRB). A data safety monitoring board (DSMB) was formulated. The study is registered at http://www.clinicaltrials.gov (NCT02190799).",2015 Nov 19,"['Arabi, Yaseen', 'Balkhy, Hanan', 'Hajeer, Ali H.', 'Bouchama, Abderrezak', 'Hayden, Frederick G.', 'Al-Omari, Awad', 'Al-Hameed, Fahad M.', 'Taha, Yusri', 'Shindo, Nahoko', 'Whitehead, John', 'Merson, Laura', 'AlJohani, Sameera', 'Al-Khairy, Khalid', 'Carson, Gail', 'Luke, Thomas C.', 'Hensley, Lisa', 'Al-Dawood, Abdulaziz', 'Al-Qahtani, Saad', 'Modjarrad, Kayvon', 'Sadat, Musharaf', 'Rohde, Gernot', 'Leport, Catherine', 'Fowler, Robert']",Springerplus,,,True
717168e782bf72b65add057c1cebe8d1bfdffbda,PMC,Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments,http://dx.doi.org/10.1371/journal.ppat.1005274,PMC4654589,26587836,CC BY,"Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus associated with various AIDS-related malignancies. Like other herpesviruses, multiple processes required for KSHV lytic replication, including viral transcription, viral DNA synthesis and capsid assembly occur in virus-induced intranuclear structures, termed replication and transcription compartments (RTCs). Here we utilised a novel methodology, combining subcellular fractionation and quantitative proteomics, to identify cellular proteins which are recruited to KSHV-induced RTCs and thus play a key role in KSHV lytic replication. We show that several isoforms of the HSP70 chaperone family, Hsc70 and iHsp70, are redistributed from the cytoplasm into the nucleus coinciding with the initial formation of KSHV-induced RTCs. We demonstrate that nuclear chaperone foci are dynamic, initially forming adjacent to newly formed KSHV RTCs, however during later time points the chaperones move within KSHV RTCs and completely co-localise with actively replicating viral DNA. The functional significance of Hsp70 isoforms recruitment into KSHV RTCs was also examined using the specific Hsp70 isoform small molecule inhibitor, VER-155008. Intriguingly, results highlight an essential role of Hsp70 isoforms in the KSHV replication cycle independent of protein stability and maturation. Notably, inhibition of Hsp70 isoforms precluded KSHV RTC formation and RNA polymerase II (RNAPII) relocalisation to the viral genome leading to the abolishment of global KSHV transcription and subsequent viral protein synthesis and DNA replication. These new findings have revealed novel mechanisms that regulate KSHV lytic replication and highlight the potential of HSP70 inhibitors as novel antiviral agents.",2015 Nov 20,"['Baquero-Pérez, Belinda', 'Whitehouse, Adrian']",PLoS Pathog,,,True
00a991c7d1c8a86b5627340206fa83d6716f34c1,PMC,Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments,http://dx.doi.org/10.1371/journal.ppat.1005274,PMC4654589,26587836,CC BY,"Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus associated with various AIDS-related malignancies. Like other herpesviruses, multiple processes required for KSHV lytic replication, including viral transcription, viral DNA synthesis and capsid assembly occur in virus-induced intranuclear structures, termed replication and transcription compartments (RTCs). Here we utilised a novel methodology, combining subcellular fractionation and quantitative proteomics, to identify cellular proteins which are recruited to KSHV-induced RTCs and thus play a key role in KSHV lytic replication. We show that several isoforms of the HSP70 chaperone family, Hsc70 and iHsp70, are redistributed from the cytoplasm into the nucleus coinciding with the initial formation of KSHV-induced RTCs. We demonstrate that nuclear chaperone foci are dynamic, initially forming adjacent to newly formed KSHV RTCs, however during later time points the chaperones move within KSHV RTCs and completely co-localise with actively replicating viral DNA. The functional significance of Hsp70 isoforms recruitment into KSHV RTCs was also examined using the specific Hsp70 isoform small molecule inhibitor, VER-155008. Intriguingly, results highlight an essential role of Hsp70 isoforms in the KSHV replication cycle independent of protein stability and maturation. Notably, inhibition of Hsp70 isoforms precluded KSHV RTC formation and RNA polymerase II (RNAPII) relocalisation to the viral genome leading to the abolishment of global KSHV transcription and subsequent viral protein synthesis and DNA replication. These new findings have revealed novel mechanisms that regulate KSHV lytic replication and highlight the potential of HSP70 inhibitors as novel antiviral agents.",2015 Nov 20,"['Baquero-Pérez, Belinda', 'Whitehouse, Adrian']",PLoS Pathog,,,False
6ca67aad56774445edd862e8c6ac12bc38673278,PMC,Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments,http://dx.doi.org/10.1371/journal.ppat.1005274,PMC4654589,26587836,CC BY,"Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus associated with various AIDS-related malignancies. Like other herpesviruses, multiple processes required for KSHV lytic replication, including viral transcription, viral DNA synthesis and capsid assembly occur in virus-induced intranuclear structures, termed replication and transcription compartments (RTCs). Here we utilised a novel methodology, combining subcellular fractionation and quantitative proteomics, to identify cellular proteins which are recruited to KSHV-induced RTCs and thus play a key role in KSHV lytic replication. We show that several isoforms of the HSP70 chaperone family, Hsc70 and iHsp70, are redistributed from the cytoplasm into the nucleus coinciding with the initial formation of KSHV-induced RTCs. We demonstrate that nuclear chaperone foci are dynamic, initially forming adjacent to newly formed KSHV RTCs, however during later time points the chaperones move within KSHV RTCs and completely co-localise with actively replicating viral DNA. The functional significance of Hsp70 isoforms recruitment into KSHV RTCs was also examined using the specific Hsp70 isoform small molecule inhibitor, VER-155008. Intriguingly, results highlight an essential role of Hsp70 isoforms in the KSHV replication cycle independent of protein stability and maturation. Notably, inhibition of Hsp70 isoforms precluded KSHV RTC formation and RNA polymerase II (RNAPII) relocalisation to the viral genome leading to the abolishment of global KSHV transcription and subsequent viral protein synthesis and DNA replication. These new findings have revealed novel mechanisms that regulate KSHV lytic replication and highlight the potential of HSP70 inhibitors as novel antiviral agents.",2015 Nov 20,"['Baquero-Pérez, Belinda', 'Whitehouse, Adrian']",PLoS Pathog,,,False
9f75752eb62482a4e2919951414267f541e419db,PMC,Experimental infection of a US spike-insertion deletion porcine epidemic diarrhea virus in conventional nursing piglets and cross-protection to the original US PEDV infection,http://dx.doi.org/10.1186/s13567-015-0278-9,PMC4654902,26589292,CC BY,"Although the original US porcine epidemic diarrhea virus (PEDV) was confirmed as highly virulent by multiple studies, the virulence of spike-insertion deletion (S-INDEL) PEDV strains is undefined. In this study, 3–4 day-old conventional suckling piglets were inoculated with S-INDEL PEDV Iowa106 (4 pig litters) to study its virulence. Two litters of age-matched piglets were inoculated with either the original US PEDV PC21A or mock as positive and negative controls, respectively. Subsequently, all pigs were challenged with the original US PEDV PC21A on 21–29 days post-inoculation (dpi) to assess cross-protection. All S-INDEL Iowa106- and the original US PC21A-inoculated piglets developed diarrhea. However, the severity of clinical signs, mortality (0–75%) and fecal PEDV RNA shedding titers varied among the four S-INDEL Iowa106-inoculated litters. Compared with the original PC21A, piglets euthanized/died acutely from S-INDEL Iowa106 infection had relatively milder villous atrophy, lower antigen scores and more limited intestinal infection. Two of four S-INDEL Iowa106-infected sows and the original PC21A-infected sow showed anorexia and watery diarrhea for 1–4 days. After the original PC21A challenge, a subset (13/16) of S-INDEL Iowa106-inoculated piglets developed diarrhea, whereas all (5/5) and no (0/4) pigs in the mock and original PC21A-inoculated pigs had diarrhea, respectively. Our results suggest that the virulence of S-INDEL PEDV Iowa106 was less than the original US PEDV PC21A in suckling pigs, with 100% morbidity and 18% (6/33) overall (0–75%) mortality in suckling pigs depending on factors such as the sow’s health and lactation and the piglets’ birth weight. Prior infection by S-INDEL Iowa106 provided partial cross-protection to piglets against the original PC21A challenge at 21–29 dpi.",2015 Nov 20,"['Lin, Chun-Ming', 'Annamalai, Thavamathi', 'Liu, Xinsheng', 'Gao, Xiang', 'Lu, Zhongyan', 'El-Tholoth, Mohamed', 'Hu, Hui', 'Saif, Linda J.', 'Wang, Qiuhong']",Vet Res,,,True
3065f9bd3f5cbaad08a1f0e35f5781ccd0857cd7,PMC,The influence of cold weather on the usage of emergency link calls: a case study in Hong Kong,http://dx.doi.org/10.1186/s12911-015-0191-1,PMC4654920,26590158,CC BY,"BACKGROUND: In response to an unexpected long cold spell in February 1996 which killed more than 100 older adults (mostly living alone) in Hong Kong, the Hong Kong Senior Citizen Home Safety Association established a Personal Emergency Link Service to provide emergency contact to the older adults, which uses a telephone system to render emergency relief and total care service around the clock. To facilitate the dynamic and efficient allocation of service resources, it is crucial to understand the factors linked with use of the services and number of hospital admissions arising from PE link service. METHODS: We initially use the Poisson generalized linear model (GLM) with polynomial effect functions of relevant covariates. If the time series of residuals from fitting the Poisson GLM reveals significant serial correlation, a Poisson generalized linear autoregressive moving average (GLARMA) model is refitted to the data to account for the auto-correlation among the time series of daily call numbers. If the data is overdispersed relative to the best fitting Poisson GLARMA model, then the negative binomial GLARMA model is refitted to account for any overdispersion. In all the models, dummy variables for weekdays and months are included to account for any cyclic trends due weekday effect or month of the year effect. The secular time trend is modeled by a polynomial function of calendar time over the study period. Finally any critical temperatures are identified by visually inspecting the graph of the effect function of temperature. RESULTS: The weekday and month effects are both significant with Monday seeing more PE Link calls than Sunday and June seeing less than January. Temperature has significant effect on the PE Link call rate with the effect highly nonlinear. A critical temperature, below which excessive increase in PE link calls that lead to hospital admissions, is identified to be around 15 °C. CONCLUSION: Identifying a threshold temperature which generates an excessive increase in the expected number of PE Link calls would be useful in service provision planning and support for elderly in need of hospital admission.",2015 Aug 13,"['Chen, Feng', 'Yip, Paul SF']",BMC Med Inform Decis Mak,,,True
8d5bf19e94a61fcf764faf3a9362f61e1fd2b90b,PMC,Rapid drop in the reproduction number during the Ebola outbreak in the Democratic Republic of Congo,http://dx.doi.org/10.7717/peerj.1418,PMC4655090,26618087,CC BY,"The Democratic Republic of Congo (DRC) experienced a confined rural outbreak of Ebola virus disease (EVD) with 69 reported cases from July to October 2014. Understanding the transmission dynamics during the outbreak can provide important information for anticipating and controlling future EVD epidemics. I fitted an EVD transmission model to previously published data of this outbreak and estimated the basic reproduction number R(0) = 5.2 (95% CI [4.0–6.7]). The model suggests that the net reproduction number R(t) fell below unity 28 days (95% CI [25–34] days) after the onset of symptoms in the index case. This study adds to previous epidemiological descriptions of the 2014 EVD outbreak in DRC, and is consistent with the notion that a rapid implementation of control interventions helped reduce further spread.",2015 Nov 19,"Althaus, Christian L.",PeerJ,,,False
173c216511cdf5174a09140aca928d1a83d8c916,PMC,Rapid drop in the reproduction number during the Ebola outbreak in the Democratic Republic of Congo,http://dx.doi.org/10.7717/peerj.1418,PMC4655090,26618087,CC BY,"The Democratic Republic of Congo (DRC) experienced a confined rural outbreak of Ebola virus disease (EVD) with 69 reported cases from July to October 2014. Understanding the transmission dynamics during the outbreak can provide important information for anticipating and controlling future EVD epidemics. I fitted an EVD transmission model to previously published data of this outbreak and estimated the basic reproduction number R(0) = 5.2 (95% CI [4.0–6.7]). The model suggests that the net reproduction number R(t) fell below unity 28 days (95% CI [25–34] days) after the onset of symptoms in the index case. This study adds to previous epidemiological descriptions of the 2014 EVD outbreak in DRC, and is consistent with the notion that a rapid implementation of control interventions helped reduce further spread.",2015 Nov 19,"Althaus, Christian L.",PeerJ,,,False
02bfb4c09489a5f48c23e8441e37b055bf7228ee,PMC,Chikungunya nsP2 protease is not a papain-like cysteine protease and the catalytic dyad cysteine is interchangeable with a proximal serine,http://dx.doi.org/10.1038/srep17125,PMC4657084,26597768,CC BY,"Chikungunya virus is the pathogenic alphavirus that causes chikungunya fever in humans. In the last decade millions of cases have been reported around the world from Africa to Asia to the Americas. The alphavirus nsP2 protein is multifunctional and is considered to be pivotal to viral replication, as the nsP2 protease activity is critical for proteolytic processing of the viral polyprotein during replication. Classically the alphavirus nsP2 protease is thought to be papain-like with the enzyme reaction proceeding through a cysteine/histidine catalytic dyad. We performed structure-function studies on the chikungunya nsP2 protease and show that the enzyme is not papain-like. Characterization of the catalytic dyad cysteine residue enabled us to identify a nearby serine that is catalytically interchangeable with the dyad cysteine residue. The enzyme retains activity upon alanine replacement of either residue but a replacement of both cysteine and serine residues results in no detectable activity. Protein dynamics appears to allow the use of either the cysteine or the serine residue in catalysis. This switchable dyad residue has not been previously reported for alphavirus nsP2 proteases and would have a major impact on the nsP2 protease as an anti-viral target.",2015 Nov 24,"['Saisawang, Chonticha', 'Saitornuang, Sawanan', 'Sillapee, Pornpan', 'Ubol, Sukathida', 'Smith, Duncan R.', 'Ketterman, Albert J.']",Sci Rep,,,True
458c9e598bc8757d58a592739384d70ae4560a50,PMC,Amelioration of Japanese encephalitis by blockage of 4-1BB signaling is coupled to divergent enhancement of type I/II IFN responses and Ly-6C(hi) monocyte differentiation,http://dx.doi.org/10.1186/s12974-015-0438-x,PMC4657197,26597582,CC BY,"BACKGROUND: Japanese encephalitis (JE), a neuroinflammation caused by zoonotic JE virus, is the major cause of viral encephalitis worldwide and poses an increasing threat to global health and welfare. To date, however, there has been no report describing the regulation of JE progression using immunomodulatory tools for developing therapeutic strategies. We tested whether blocking the 4-1BB signaling pathway would regulate JE progression using murine JE model. METHODS: Infected wild-type and 4-1BB-knockout (KO) mice were examined daily for mortality and clinical signs, and neuroinflammation in the CNS was evaluated by infiltration of inflammatory leukocytes and cytokine expression. In addition, viral burden, JEV-specific T cell, and type I/II IFN (IFN-I/II) innate responses were analyzed. RESULTS: Blocking the 4-1BB signaling pathway significantly increased resistance to JE and reduced viral burden in extraneural tissues and the CNS, rather than causing a detrimental effect. In addition, treatment with 4-1BB agonistic antibody exacerbated JE. Furthermore, JE amelioration and reduction of viral burden by blocking the 4-1BB signaling pathway were associated with an increased frequency of IFN-II-producing NK and CD4(+) Th1 cells as well as increased infiltration of mature Ly-6C(hi) monocytes in the inflamed CNS. More interestingly, DCs and macrophages derived from 4-1BB KO mice showed potent and rapid IFN-I innate immune responses upon JEV infection, which was coupled to strong induction of PRRs (RIG-I, MDA5), transcription factors (IRF7), and antiviral ISG genes (ISG49, ISG54, ISG56). Further, the ablation of 4-1BB signaling enhanced IFN-I innate responses in neuron cells, which likely regulated viral spread in the CNS. Finally, we confirmed that blocking the 4-1BB signaling pathway in myeloid cells derived from hematopoietic stem cells (HSCs) played a dominant role in ameliorating JE. In support of this finding, HSC-derived leukocytes played a dominant role in generating the IFN-I innate responses in the host. CONCLUSIONS: Blocking the 4-1BB signaling pathway ameliorates JE via divergent enhancement of IFN-II-producing NK and CD4(+) Th1 cells and mature Ly-6C(hi) monocyte infiltration, as well as an IFN-I innate response of myeloid-derived cells. Therefore, regulation of the 4-1BB signaling pathway with antibodies or inhibitors could be a valuable therapeutic strategy for the treatment of JE.",2015 Nov 24,"['Kim, Seong Bum', 'Choi, Jin Young', 'Kim, Jin Hyoung', 'Uyangaa, Erdenebelig', 'Patil, Ajit Mahadev', 'Park, Sang-Youel', 'Lee, John Hwa', 'Kim, Koanhoi', 'Han, Young Woo', 'Eo, Seong Kug']",J Neuroinflammation,,,True
36469337a42a7feb9bdefa958b364d2e269ec2ae,PMC,Rapid detection of the common avian leukosis virus subgroups by real-time loop-mediated isothermal amplification,http://dx.doi.org/10.1186/s12985-015-0430-1,PMC4657318,26596553,CC BY,"BACKGROUND: Subgroups A, B, E and J are the major subgroups of avian leukosis virus (ALV) infecting chickens. ALV infection has become endemic in China and has a significant negative effect on the poultry industry. Consequently, there is an urgent need for a specific, sensitive and rapid method for diagnosis and eradication of ALV. Therefore, we developed a simple and rapid real-time loop-mediated isothermal amplification (LAMP) reaction for the timely detection of the common ALV subgroups, whereby the amplification can be obtained in 35 min under isothermal conditions at 63 °C, ability to specific, sensitive and rapid detect all the common ALV subgroups. METHODS: A set of four specific primers was designed to target the sequences of the pol gene of ALV, and the loop-mediated isothermal amplification (LAMP) assay were developed and compared with PCR and virus isolation methods. RESULTS: The results from specificity of the LAMP assay showed that only target ALVs DNA was amplified. The LAMP assay demonstrated a sensitivity of 20 copies/reaction of ALV DNA, which was 10 times higher than the conventional PCR measurement. To further evaluate the reliability of the method, the assay was evaluated with ALV DNA from a panel of 81 clinical samples suspected of ALV infection. The results verify that the LAMP method was more sensitive than the conventional PCR and virus isolation method. CONCLUSION: In conclusion, the developed LAMP assay was a simple, inexpensive, sensitive method for the rapid detection of the most common subgroups of ALV, and it provided a useful and practical tool in the eradication program for ALV in the poultry industry.",2015 Nov 24,"['Peng, Hao', 'Qin, Lili', 'Bi, Yuyu', 'Wang, Peikun', 'Zou, Guangzhen', 'Li, Jun', 'Yang, Yongli', 'Zhong, Xingfu', 'Wei, Ping']",Virol J,,,True
a63d851872c31a91cf814a84fc2af7f4fb15ce3d,PMC,A parallel genome-wide RNAi screening strategy to identify host proteins important for entry of Marburg virus and H5N1 influenza virus,http://dx.doi.org/10.1186/s12985-015-0420-3,PMC4657351,26596270,CC BY,"BACKGROUND: Genome-wide RNAi screening has been widely used to identify host proteins involved in replication and infection of different viruses, and numerous host factors are implicated in the replication cycles of these viruses, demonstrating the power of this approach. However, discrepancies on target identification of the same viruses by different groups suggest that high throughput RNAi screening strategies need to be carefully designed, developed and optimized prior to the large scale screening. METHODS: Two genome-wide RNAi screens were performed in parallel against the entry of pseudotyped Marburg viruses and avian influenza virus H5N1 utilizing an HIV-1 based surrogate system, to identify host factors which are important for virus entry. A comparative analysis approach was employed in data analysis, which alleviated systematic positional effects and reduced the false positive number of virus-specific hits. RESULTS: The parallel nature of the strategy allows us to easily identify the host factors for a specific virus with a greatly reduced number of false positives in the initial screen, which is one of the major problems with high throughput screening. The power of this strategy is illustrated by a genome-wide RNAi screen for identifying the host factors important for Marburg virus and/or avian influenza virus H5N1 as described in this study. CONCLUSIONS: This strategy is particularly useful for highly pathogenic viruses since pseudotyping allows us to perform high throughput screens in the biosafety level 2 (BSL-2) containment instead of the BSL-3 or BSL-4 for the infectious viruses, with alleviated safety concerns. The screening strategy together with the unique comparative analysis approach makes the data more suitable for hit selection and enables us to identify virus-specific hits with a much lower false positive rate.",2015 Nov 24,"['Cheng, Han', 'Koning, Katie', 'O’Hearn, Aileen', 'Wang, Minxiu', 'Rumschlag-Booms, Emily', 'Varhegyi, Elizabeth', 'Rong, Lijun']",Virol J,,,True
0a4f344f96d5a21e3d0f33e199983738c37a1631,PMC,The Impact of Human Mobility on HIV Transmission in Kenya,http://dx.doi.org/10.1371/journal.pone.0142805,PMC4657931,26599277,CC BY,"Disease spreads as a result of people moving and coming in contact with each other. Thus the mobility patterns of individuals are crucial in understanding disease dynamics. Here we study the impact of human mobility on HIV transmission in different parts of Kenya. We build an SIR metapopulation model that incorporates the different regions within the country. We parameterise the model using census data, HIV data and mobile phone data adopted to track human mobility. We found that movement between different regions appears to have a relatively small overall effect on the total increase in HIV cases in Kenya. However, the most important consequence of movement patterns was transmission of the disease from high infection to low prevalence areas. Mobility slightly increases HIV incidence rates in regions with initially low HIV prevalences and slightly decreases incidences in regions with initially high HIV prevalence. We discuss how regional HIV models could be used in public-health planning. This paper is a first attempt to model spread of HIV using mobile phone data, and we also discuss limitations to the approach.",2015 Nov 24,"['Isdory, Augustino', 'Mureithi, Eunice W.', 'Sumpter, David J. T.']",PLoS One,,,True
6c4f3eeb65df5c4294024c37835fa5097dd604e7,PMC,The Impact of Human Mobility on HIV Transmission in Kenya,http://dx.doi.org/10.1371/journal.pone.0142805,PMC4657931,26599277,CC BY,"Disease spreads as a result of people moving and coming in contact with each other. Thus the mobility patterns of individuals are crucial in understanding disease dynamics. Here we study the impact of human mobility on HIV transmission in different parts of Kenya. We build an SIR metapopulation model that incorporates the different regions within the country. We parameterise the model using census data, HIV data and mobile phone data adopted to track human mobility. We found that movement between different regions appears to have a relatively small overall effect on the total increase in HIV cases in Kenya. However, the most important consequence of movement patterns was transmission of the disease from high infection to low prevalence areas. Mobility slightly increases HIV incidence rates in regions with initially low HIV prevalences and slightly decreases incidences in regions with initially high HIV prevalence. We discuss how regional HIV models could be used in public-health planning. This paper is a first attempt to model spread of HIV using mobile phone data, and we also discuss limitations to the approach.",2015 Nov 24,"['Isdory, Augustino', 'Mureithi, Eunice W.', 'Sumpter, David J. T.']",PLoS One,,,True
0a9983132b38156cea8ed9e4313d270120f2731e,PMC,The Impact of Human Mobility on HIV Transmission in Kenya,http://dx.doi.org/10.1371/journal.pone.0142805,PMC4657931,26599277,CC BY,"Disease spreads as a result of people moving and coming in contact with each other. Thus the mobility patterns of individuals are crucial in understanding disease dynamics. Here we study the impact of human mobility on HIV transmission in different parts of Kenya. We build an SIR metapopulation model that incorporates the different regions within the country. We parameterise the model using census data, HIV data and mobile phone data adopted to track human mobility. We found that movement between different regions appears to have a relatively small overall effect on the total increase in HIV cases in Kenya. However, the most important consequence of movement patterns was transmission of the disease from high infection to low prevalence areas. Mobility slightly increases HIV incidence rates in regions with initially low HIV prevalences and slightly decreases incidences in regions with initially high HIV prevalence. We discuss how regional HIV models could be used in public-health planning. This paper is a first attempt to model spread of HIV using mobile phone data, and we also discuss limitations to the approach.",2015 Nov 24,"['Isdory, Augustino', 'Mureithi, Eunice W.', 'Sumpter, David J. T.']",PLoS One,,,False
678b0f0a0a510ad2dc7a7c9ab6677172168094d0,PMC,The Impact of Human Mobility on HIV Transmission in Kenya,http://dx.doi.org/10.1371/journal.pone.0142805,PMC4657931,26599277,CC BY,"Disease spreads as a result of people moving and coming in contact with each other. Thus the mobility patterns of individuals are crucial in understanding disease dynamics. Here we study the impact of human mobility on HIV transmission in different parts of Kenya. We build an SIR metapopulation model that incorporates the different regions within the country. We parameterise the model using census data, HIV data and mobile phone data adopted to track human mobility. We found that movement between different regions appears to have a relatively small overall effect on the total increase in HIV cases in Kenya. However, the most important consequence of movement patterns was transmission of the disease from high infection to low prevalence areas. Mobility slightly increases HIV incidence rates in regions with initially low HIV prevalences and slightly decreases incidences in regions with initially high HIV prevalence. We discuss how regional HIV models could be used in public-health planning. This paper is a first attempt to model spread of HIV using mobile phone data, and we also discuss limitations to the approach.",2015 Nov 24,"['Isdory, Augustino', 'Mureithi, Eunice W.', 'Sumpter, David J. T.']",PLoS One,,,False
da15b43c189e131680b837f08b9df2137739d874,PMC,The Impact of Human Mobility on HIV Transmission in Kenya,http://dx.doi.org/10.1371/journal.pone.0142805,PMC4657931,26599277,CC BY,"Disease spreads as a result of people moving and coming in contact with each other. Thus the mobility patterns of individuals are crucial in understanding disease dynamics. Here we study the impact of human mobility on HIV transmission in different parts of Kenya. We build an SIR metapopulation model that incorporates the different regions within the country. We parameterise the model using census data, HIV data and mobile phone data adopted to track human mobility. We found that movement between different regions appears to have a relatively small overall effect on the total increase in HIV cases in Kenya. However, the most important consequence of movement patterns was transmission of the disease from high infection to low prevalence areas. Mobility slightly increases HIV incidence rates in regions with initially low HIV prevalences and slightly decreases incidences in regions with initially high HIV prevalence. We discuss how regional HIV models could be used in public-health planning. This paper is a first attempt to model spread of HIV using mobile phone data, and we also discuss limitations to the approach.",2015 Nov 24,"['Isdory, Augustino', 'Mureithi, Eunice W.', 'Sumpter, David J. T.']",PLoS One,,,False
d7c55372bf569553c20217248e0ca3260ff007cf,PMC,The Impact of Human Mobility on HIV Transmission in Kenya,http://dx.doi.org/10.1371/journal.pone.0142805,PMC4657931,26599277,CC BY,"Disease spreads as a result of people moving and coming in contact with each other. Thus the mobility patterns of individuals are crucial in understanding disease dynamics. Here we study the impact of human mobility on HIV transmission in different parts of Kenya. We build an SIR metapopulation model that incorporates the different regions within the country. We parameterise the model using census data, HIV data and mobile phone data adopted to track human mobility. We found that movement between different regions appears to have a relatively small overall effect on the total increase in HIV cases in Kenya. However, the most important consequence of movement patterns was transmission of the disease from high infection to low prevalence areas. Mobility slightly increases HIV incidence rates in regions with initially low HIV prevalences and slightly decreases incidences in regions with initially high HIV prevalence. We discuss how regional HIV models could be used in public-health planning. This paper is a first attempt to model spread of HIV using mobile phone data, and we also discuss limitations to the approach.",2015 Nov 24,"['Isdory, Augustino', 'Mureithi, Eunice W.', 'Sumpter, David J. T.']",PLoS One,,,False
90f28a7925b8350d3a484cac6ed454a328d08b67,PMC,Epidemiology of Enterovirus D68 in Ontario,http://dx.doi.org/10.1371/journal.pone.0142841,PMC4658075,26599365,CC BY,"In August 2014, children’s hospitals in Kansas City, Missouri and Chicago, Illinois notified the Centers for Disease Control and Prevention (CDC) about increased numbers of pediatric patients hospitalized with severe respiratory illness (SRI). In response to CDC reports, Public Health Ontario Laboratories (PHOL) launched an investigation of patients being tested for enterovirus D-68 (EV-D68) in Ontario, Canada. The purpose of this investigation was to enhance our understanding of EV-D68 epidemiology and clinical features. Data for this study included specimens submitted for EV-D68 testing at PHOL from September 1, 2014 to October 31, 2014. Comparisons were made between patients who tested positive for the virus (cases) and those testing negative (controls). EV-D68 was identified in 153/907 (16.8%) of patients tested. In the logistic regression model adjusting for age, sex, setting and time to specimen collection, individuals younger than 20 years of age were more likely to be diagnosed with EV-D68 compared to those 20 and over, with peak positivity at ages 5–9 years. Cases were not more likely to be hospitalized than controls. Cases were more likely to be identified in September than October (OR 8.07; 95% CI 5.15 to 12.64). Routine viral culture and multiplex PCR were inadequate methods to identify EV-D68 due to poor sensitivity and inability to differentiate EV-D68 from other enterovirus serotypes or rhinovirus. Testing for EV-D68 in Ontario from July to December, 2014 detected the presence of EV-D68 virus among young children during September-October, 2014, with most cases detected in September. There was no difference in hospitalization status between cases and controls. In order to better understand the epidemiology of this virus, surveillance for EV-D68 should include testing of symptomatic individuals from all treatment settings and patient age groups, with collection and analysis of comprehensive clinical and epidemiological data.",2015 Nov 23,"['Peci, Adriana', 'Winter, Anne-Luise', 'Warshawsky, Bryna', 'Booth, Tim F.', 'Eshaghi, AliReza', 'Li, Aimin', 'Perusini, Stephen', 'Olsha, Romy', 'Marchand-Austin, Alex', 'Kristjanson, Erik', 'Gubbay, Jonathan B.']",PLoS One,,,True
96c1bc8e891b94c919d20cd97d00b3790fc6d2b3,PMC,Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage,http://dx.doi.org/10.1016/j.immuni.2015.10.013,PMC4658338,26588782,CC BY,"Tissue damage caused by viral hepatitis is a major cause of morbidity and mortality worldwide. Using a mouse model of viral hepatitis, we identified virus-induced early transcriptional changes in the redox pathways in the liver, including downregulation of superoxide dismutase 1 (Sod1). Sod1(−/−) mice exhibited increased inflammation and aggravated liver damage upon viral infection, which was independent of T and NK cells and could be ameliorated by antioxidant treatment. Type I interferon (IFN-I) led to a downregulation of Sod1 and caused oxidative liver damage in Sod1(−/−) and wild-type mice. Genetic and pharmacological ablation of the IFN-I signaling pathway protected against virus-induced liver damage. These results delineate IFN-I mediated oxidative stress as a key mediator of virus-induced liver damage and describe a mechanism of innate-immunity-driven pathology, linking IFN-I signaling with antioxidant host defense and infection-associated tissue damage. VIDEO ABSTRACT:",2015 Nov 17,"['Bhattacharya, Anannya', 'Hegazy, Ahmed\xa0N.', 'Deigendesch, Nikolaus', 'Kosack, Lindsay', 'Cupovic, Jovana', 'Kandasamy, Richard\xa0K.', 'Hildebrandt, Andrea', 'Merkler, Doron', 'Kühl, Anja\xa0A.', 'Vilagos, Bojan', 'Schliehe, Christopher', 'Panse, Isabel', 'Khamina, Kseniya', 'Baazim, Hatoon', 'Arnold, Isabelle', 'Flatz, Lukas', 'Xu, Haifeng\xa0C.', 'Lang, Philipp\xa0A.', 'Aderem, Alan', 'Takaoka, Akinori', 'Superti-Furga, Giulio', 'Colinge, Jacques', 'Ludewig, Burkhard', 'Löhning, Max', 'Bergthaler, Andreas']",Immunity,,,False
2034ca5a9941b6e3d8b0ba9280a5b2fae192778d,PMC,Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage,http://dx.doi.org/10.1016/j.immuni.2015.10.013,PMC4658338,26588782,CC BY,"Tissue damage caused by viral hepatitis is a major cause of morbidity and mortality worldwide. Using a mouse model of viral hepatitis, we identified virus-induced early transcriptional changes in the redox pathways in the liver, including downregulation of superoxide dismutase 1 (Sod1). Sod1(−/−) mice exhibited increased inflammation and aggravated liver damage upon viral infection, which was independent of T and NK cells and could be ameliorated by antioxidant treatment. Type I interferon (IFN-I) led to a downregulation of Sod1 and caused oxidative liver damage in Sod1(−/−) and wild-type mice. Genetic and pharmacological ablation of the IFN-I signaling pathway protected against virus-induced liver damage. These results delineate IFN-I mediated oxidative stress as a key mediator of virus-induced liver damage and describe a mechanism of innate-immunity-driven pathology, linking IFN-I signaling with antioxidant host defense and infection-associated tissue damage. VIDEO ABSTRACT:",2015 Nov 17,"['Bhattacharya, Anannya', 'Hegazy, Ahmed\xa0N.', 'Deigendesch, Nikolaus', 'Kosack, Lindsay', 'Cupovic, Jovana', 'Kandasamy, Richard\xa0K.', 'Hildebrandt, Andrea', 'Merkler, Doron', 'Kühl, Anja\xa0A.', 'Vilagos, Bojan', 'Schliehe, Christopher', 'Panse, Isabel', 'Khamina, Kseniya', 'Baazim, Hatoon', 'Arnold, Isabelle', 'Flatz, Lukas', 'Xu, Haifeng\xa0C.', 'Lang, Philipp\xa0A.', 'Aderem, Alan', 'Takaoka, Akinori', 'Superti-Furga, Giulio', 'Colinge, Jacques', 'Ludewig, Burkhard', 'Löhning, Max', 'Bergthaler, Andreas']",Immunity,,,True
dde2f725f681ca3d6af28e816b5b58db9fe56551,PMC,"Social support and HIV/STDs infections among a probability-based sample of rural married migrant women in Shandong Province, China",http://dx.doi.org/10.1186/s12889-015-2508-5,PMC4658759,26603036,CC BY,"BACKGROUND: The increasing population of marriage-based migrant women is disproportionally affected by AIDS/STDs in China, and social support plays a critical role. This study aims to describe the social support level received by married migrant women in rural areas in Shandong province in comparison to non-migrant local women, identifies the relevant factors of this social support condition among married migrant women, and observes the correlation between social support level and infection status of AIDS and STDs among this group. METHODS: A probability-based sample of 1,076 migrant and 1,195 local women were included in the study. A pre-tested field questionnaire was administered to participants through a direct face-to-face interview. Questionnaire contained questions on socio-demographic information, AIDS and STDs prevalence information and Social Support Rating Scale (SSRS) which measures objective support, subjective support, and utilization of social support. RESULTS: Compared to local women, married migrant women had lower levels of social support in most dimensions. Multi-variable analysis revealed that relationship with spouse, family average income, number of children, education, engagement and claimed reasons of moving have various correlations with one or all dimensions of social support scores. Higher social support is also related to awareness of infection status of HIV and STDs among this group. CONCLUSION: Our findings provide further evidence that married migrant women have lower levels of social support which may be related to some social characteristics and their awareness status of AIDS and STDs infection status and that targeted interventions need to be developed for this population.",2015 Nov 24,"['Ma, Wenkang', 'Kang, Dianmin', 'Song, Yapei', 'Wei, Chongyi', 'Marley, Gifty', 'Ma, Wei']",BMC Public Health,,,True
4b130b88bd3514c7159a9c25c0f52e4a531950e5,PMC,Changes in microbiota during experimental human Rhinovirus infection,http://dx.doi.org/10.1186/s12879-015-1081-y,PMC4659412,26271750,CC BY,"BACKGROUND: Human Rhinovirus (HRV) is responsible for the majority of common colds and is frequently accompanied by secondary bacterial infections through poorly understood mechanisms. We investigated the effects of experimental human HRV serotype 16 infection on the upper respiratory tract microbiota. METHODS: Six healthy volunteers were infected with HRV16. We performed 16S ribosomal RNA-targeted pyrosequencing on throat swabs taken prior, during and after infection. We compared overall community diversity, phylogenetic structure of the ecosystem and relative abundances of the different bacteria between time points. RESULTS: During acute infection strong trends towards increases in the relative abundances of Haemophilus parainfluenzae and Neisseria subflava were observed, as well as a weaker trend towards increases of Staphylococcus aureus. No major differences were observed between day-1 and day 60, whereas differences between subjects were very high. CONCLUSIONS: HRV16 infection is associated with the increase of three genera known to be associated with secondary infections following HRV infections. The observed changes of upper respiratory tract microbiota could help explain why HRV infection predisposes to bacterial otitis media, sinusitis and pneumonia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1081-y) contains supplementary material, which is available to authorized users.",2015 Aug 14,"['Hofstra, J. J.', 'Matamoros, S.', 'van de Pol, M. A.', 'de Wever, B.', 'Tanck, M. W.', 'Wendt-Knol, H.', 'Deijs, M.', 'van der Hoek, L.', 'Wolthers, K. C.', 'Molenkamp, R.', 'Visser, C. E.', 'Sterk, P. J.', 'Lutter, R.', 'de Jong, M. D.']",BMC Infect Dis,,,True
83e137405afc87914e9128afa5aec46cc2b152cd,PMC,Seroepidemiologic Survey of Potential Pathogens in Obligate and Facultative Scavenging Avian Species in California,http://dx.doi.org/10.1371/journal.pone.0143018,PMC4659623,26606755,CC BY,"Throughout the world, populations of scavenger birds are declining rapidly with some populations already on the brink of extinction. Much of the current research into the factors contributing to these declines has focused on exposure to drug residues, lead, and other toxins. Despite increased monitoring of these declining populations, little is known about infectious diseases affecting scavenger bird species. To assess potential infectious disease risks to both obligate and facultative scavenger bird species, we performed a serosurvey for eleven potential pathogens in three species of scavenging birds in California: the California condor (Gymnogyps californianus), turkey vulture (Cathartes aura) and golden eagle (Aquila chrysaetos). California condors were seropositive for avian adenovirus, infectious bronchitis virus, Mycoplasma gallisepticum, avian paramyxovirus-2, West Nile virus (WNV) and Toxoplasma gondii. Golden eagles were seropositive for avian adenovirus, Chlamydophila psittaci and Toxoplasma gondii, and turkey vultures were seropositive for avian adenovirus, Chlamydophila psittaci, avian paramyxovirus-1, Toxoplasma gondii and WNV. Risk factor analyses indicated that rearing site and original release location were significantly associated with a positive serologic titer to WNV among free-flying condors. This study provides preliminary baseline data on infectious disease exposure in these populations for aiding in early disease detection and provides potentially critical information for conservation of the endangered California condor as it continues to expand its range and encounter new infectious disease threats.",2015 Nov 25,"['Straub, Mary H.', 'Kelly, Terra R.', 'Rideout, Bruce A.', 'Eng, Curtis', 'Wynne, Janna', 'Braun, Josephine', 'Johnson, Christine K.']",PLoS One,,,True
d85a85112817de11b60dd2e8f8177a48c3015442,PMC,Vaccines Through Centuries: Major Cornerstones of Global Health,http://dx.doi.org/10.3389/fpubh.2015.00269,PMC4659912,26636066,CC BY,"Multiple cornerstones have shaped the history of vaccines, which may contain live-attenuated viruses, inactivated organisms/viruses, inactivated toxins, or merely segments of the pathogen that could elicit an immune response. The story began with Hippocrates 400 B.C. with his description of mumps and diphtheria. No further discoveries were recorded until 1100 A.D. when the smallpox vaccine was described. During the eighteenth century, vaccines for cholera and yellow fever were reported and Edward Jenner, the father of vaccination and immunology, published his work on smallpox. The nineteenth century was a major landmark, with the “Germ Theory of disease” of Louis Pasteur, the discovery of the germ tubercle bacillus for tuberculosis by Robert Koch, and the isolation of pneumococcus organism by George Miller Sternberg. Another landmark was the discovery of diphtheria toxin by Emile Roux and its serological treatment by Emil Von Behring and Paul Ehrlih. In addition, Pasteur was able to generate the first live-attenuated viral vaccine against rabies. Typhoid vaccines were then developed, followed by the plague vaccine of Yersin. At the beginning of World War I, the tetanus toxoid was introduced, followed in 1915 by the pertussis vaccine. In 1974, The Expanded Program of Immunization was established within the WHO for bacille Calmette–Guerin, Polio, DTP, measles, yellow fever, and hepatitis B. The year 1996 witnessed the launching of the International AIDS Vaccine Initiative. In 1988, the WHO passed a resolution to eradicate polio by the year 2000 and in 2006; the first vaccine to prevent cervical cancer was developed. In 2010, “The Decade of vaccines” was launched, and on April 1st 2012, the United Nations launched the “shot@Life” campaign. In brief, the armamentarium of vaccines continues to grow with more emphasis on safety, availability, and accessibility. This mini review highlights the major historical events and pioneers in the course of development of vaccines, which have eradicated so many life-threatening diseases, despite the vaccination attitudes and waves appearing through history.",2015 Nov 26,"['Hajj Hussein, Inaya', 'Chams, Nour', 'Chams, Sana', 'El Sayegh, Skye', 'Badran, Reina', 'Raad, Mohamad', 'Gerges-Geagea, Alice', 'Leone, Angelo', 'Jurjus, Abdo']",Front Public Health,,,True
4149c3d415d6963eb002ec43810b5b4a97838465,PMC,X-ray structure and activities of an essential Mononegavirales L-protein domain,http://dx.doi.org/10.1038/ncomms9749,PMC4659945,26549102,CC BY,"The L protein of mononegaviruses harbours all catalytic activities for genome replication and transcription. It contains six conserved domains (CR-I to -VI; Fig. 1a). CR-III has been linked to polymerase and polyadenylation activity, CR-V to mRNA capping and CR-VI to cap methylation. However, how these activities are choreographed is poorly understood. Here we present the 2.2-Å X-ray structure and activities of CR-VI+, a portion of human Metapneumovirus L consisting of CR-VI and the poorly conserved region at its C terminus, the +domain. The CR-VI domain has a methyltransferase fold, which besides the typical S-adenosylmethionine-binding site ((SAM)P) also contains a novel pocket ((NS)P) that can accommodate a nucleoside. CR-VI lacks an obvious cap-binding site, and the (SAM)P-adjoining site holding the nucleotides undergoing methylation ((SUB)P) is unusually narrow because of the overhanging +domain. CR-VI+ sequentially methylates caps at their 2′O and N7 positions, and also displays nucleotide triphosphatase activity.",2015 Nov 9,"['Paesen, Guido C.', 'Collet, Axelle', 'Sallamand, Corinne', 'Debart, Françoise', 'Vasseur, Jean-Jacques', 'Canard, Bruno', 'Decroly, Etienne', 'Grimes, Jonathan M.']",Nat Commun,,,True
3801133ed6765a0ef28482c6b0d7e220340817c6,PMC,X-ray structure and activities of an essential Mononegavirales L-protein domain,http://dx.doi.org/10.1038/ncomms9749,PMC4659945,26549102,CC BY,"The L protein of mononegaviruses harbours all catalytic activities for genome replication and transcription. It contains six conserved domains (CR-I to -VI; Fig. 1a). CR-III has been linked to polymerase and polyadenylation activity, CR-V to mRNA capping and CR-VI to cap methylation. However, how these activities are choreographed is poorly understood. Here we present the 2.2-Å X-ray structure and activities of CR-VI+, a portion of human Metapneumovirus L consisting of CR-VI and the poorly conserved region at its C terminus, the +domain. The CR-VI domain has a methyltransferase fold, which besides the typical S-adenosylmethionine-binding site ((SAM)P) also contains a novel pocket ((NS)P) that can accommodate a nucleoside. CR-VI lacks an obvious cap-binding site, and the (SAM)P-adjoining site holding the nucleotides undergoing methylation ((SUB)P) is unusually narrow because of the overhanging +domain. CR-VI+ sequentially methylates caps at their 2′O and N7 positions, and also displays nucleotide triphosphatase activity.",2015 Nov 9,"['Paesen, Guido C.', 'Collet, Axelle', 'Sallamand, Corinne', 'Debart, Françoise', 'Vasseur, Jean-Jacques', 'Canard, Bruno', 'Decroly, Etienne', 'Grimes, Jonathan M.']",Nat Commun,,,False
c65fdbefc02d44dbadad79451a6253465f075837,PMC,Inferring the hosts of coronavirus using dual statistical models based on nucleotide composition,http://dx.doi.org/10.1038/srep17155,PMC4660426,26607834,CC BY,"Many coronaviruses are capable of interspecies transmission. Some of them have caused worldwide panic as emerging human pathogens in recent years, e.g., severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In order to assess their threat to humans, we explored to infer the potential hosts of coronaviruses using a dual-model approach based on nineteen parameters computed from spike genes of coronaviruses. Both the support vector machine (SVM) model and the Mahalanobis distance (MD) discriminant model achieved high accuracies in leave-one-out cross-validation of training data consisting of 730 representative coronaviruses (99.86% and 98.08% respectively). Predictions on 47 additional coronaviruses precisely conformed to conclusions or speculations by other researchers. Our approach is implemented as a web server that can be accessed at http://bioinfo.ihb.ac.cn/seq2hosts.",2015 Nov 26,"['Tang, Qin', 'Song, Yulong', 'Shi, Mijuan', 'Cheng, Yingyin', 'Zhang, Wanting', 'Xia, Xiao-Qin']",Sci Rep,,,True
6389f677ca08ac014611fe48723556b78dbd8744,PMC,Inferring the hosts of coronavirus using dual statistical models based on nucleotide composition,http://dx.doi.org/10.1038/srep17155,PMC4660426,26607834,CC BY,"Many coronaviruses are capable of interspecies transmission. Some of them have caused worldwide panic as emerging human pathogens in recent years, e.g., severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In order to assess their threat to humans, we explored to infer the potential hosts of coronaviruses using a dual-model approach based on nineteen parameters computed from spike genes of coronaviruses. Both the support vector machine (SVM) model and the Mahalanobis distance (MD) discriminant model achieved high accuracies in leave-one-out cross-validation of training data consisting of 730 representative coronaviruses (99.86% and 98.08% respectively). Predictions on 47 additional coronaviruses precisely conformed to conclusions or speculations by other researchers. Our approach is implemented as a web server that can be accessed at http://bioinfo.ihb.ac.cn/seq2hosts.",2015 Nov 26,"['Tang, Qin', 'Song, Yulong', 'Shi, Mijuan', 'Cheng, Yingyin', 'Zhang, Wanting', 'Xia, Xiao-Qin']",Sci Rep,,,False
c3b24e7070067eba2414138f7532d66ae829f9be,PMC,Viral aetiology of common colds of outpatient children at primary care level and the use of antibiotics,http://dx.doi.org/10.1590/0074-02760150154,PMC4660617,26560978,CC BY,"Although antibiotics are ineffective against viral respiratory infections, studies have shown high rates of prescriptions worldwide. We conducted a study in Brazil to determine the viral aetiologies of common colds in children and to describe the use of antibiotics for these patients. Children up to 12 years with common colds were enrolled from March 2008-February 2009 at a primary care level facility and followed by regular telephone calls and medical consultations. A nasopharyngeal wash was obtained at enrollment and studied by direct fluorescence assay and polymerase chain reaction for nine different types of virus. A sample of 134 patients was obtained, median age 2.9 years (0.1-11.2 y). Respiratory viruses were detected in 73.9% (99/134) with a coinfection rate of 30.3% (30/99). Rhinovirus was the most frequent virus (53/134; 39.6%), followed by influenza (33/134; 24.6%) and respiratory syncytial virus (8/134; 13.4%). Antibiotic prescription rate was 39.6% (53/134) and 69.8% (37/53) were considered inappropriate. Patients with influenza infection received antibiotics inappropriately in a greater proportion of cases when compared to respiratory syncytial virus and rhinovirus infections (p = 0.016). The rate of inappropriate use of antibiotics was very high and patients with influenza virus infection were prescribed antibiotics inappropriately in a greater proportion of cases.",2015 Nov,"['Kamikawa, Janete', 'Granato, Celso Francisco Hernandes', 'Bellei, Nancy']",Mem Inst Oswaldo Cruz,,,True
681a8e1fb48060f3b784fb224d80d6ed43510bda,PMC,Detection of respiratory syncytial virus and rhinovirus in healthy infants,http://dx.doi.org/10.1186/s13104-015-1695-6,PMC4660840,26608824,CC BY,"BACKGROUND: Despite the research importance of rhinovirus detection in asymptomatic healthy infants, the literature remains sparse. OBJECTIVE: To investigate the prevalence of respiratory syncytial virus (RSV) and rhinovirus (and its species). METHODS: We conducted a cross-sectional study of 110 healthy, non-hospitalized infants without acute illness at an academic medical center from November 2013 through May 2014. We tested nasal swab specimens by using polymerase chain reaction and genetic sequencing. RESULTS: Overall, the median age was 3.8 months (IQR 2.0–5.1 months), 56 % were male, and 90 % were born >37 weeks. RSV was detected in nasal swabs from infants (1.8 %). By contrast, rhinovirus was detected in nasal swabs from 16 infants (14.5 %). Molecular typing assay revealed rhinovirus species: six rhinovirus-A (5.5 %), one rhinovirus-B (0.9 %), eight rhinovirus-C (7.3 %), and one untypeable (0.9 %). CONCLUSIONS: In this cross-sectional study of healthy, community-based infants, RSV was rare (<2 %) in nasal swabs, while rhinovirus was detected in 14.5 % with a predominance of rhinovirus-A and -C. These finding are important for understanding the clinical significance of rhinovirus detection among infants hospitalized for bronchiolitis.",2015 Nov 25,"['Hasegawa, Kohei', 'Linnemann, Rachel W.', 'Avadhanula, Vasanthi', 'Mansbach, Jonathan M.', 'Piedra, Pedro A.', 'Gern, James E.', 'Camargo, Carlos A.']",BMC Res Notes,,,True
d6b52e3814a78239e5b5116dad2383b6faa327e5,PMC,Reassessing Biological Threats: Implications for Cooperative Mitigation Strategies,http://dx.doi.org/10.3389/fpubh.2015.00251,PMC4663262,26649289,CC BY,"Multiple factors ranging from globalization to ecosystem disruption are presenting the global community with evolving biological threats to local, national, and global security that reach beyond the realm of traditional bioweapon threats. As a result, mitigation strategies have adapted necessarily to the increased diversity of biological threats. In general, response and preparedness strategies have largely shifted from being primarily reactive to traditional biological weapons to more proactive in nature. In this review, we briefly explore biological threats through a wider aperture, to embrace a greater appreciation of viral pathogens, antimicrobial resistance, and agricultural pathogens, and their potential to cause civil, economic, and political devastation. In addition, we discuss current mitigation strategies codified by the Global Health Security Agenda and the One Health paradigm as well as some of the available tools to assist with their sustainable implementation.",2015 Nov 30,"['Galloway, Summer Elise', 'Petzing, Stephanie Rachel', 'Young, Catharine Grace']",Front Public Health,,,True
4f47adf53fef07c0ca76beb4b100bbdfa54b2b0b,PMC,M1 of Murine Gamma-Herpesvirus 68 Induces Endoplasmic Reticulum Chaperone Production,http://dx.doi.org/10.1038/srep17228,PMC4663489,26615759,CC BY,"Viruses rely on host chaperone network to support their infection. In particular, the endoplasmic reticulum (ER) resident chaperones play key roles in synthesizing and processing viral proteins. Influx of a large amount of foreign proteins exhausts the folding capacity in ER and triggers the unfolded protein response (UPR). A fully-executed UPR comprises signaling pathways that induce ER folding chaperones, increase protein degradation, block new protein synthesis and may eventually activate apoptosis, presenting both opportunities and threats to the virus. Here, we define a role of the MHV-68M1 gene in differential modulation of UPR pathways to enhance ER chaperone production. Ectopic expression of M1 markedly induces ER chaperone genes and expansion of ER. The M1 protein accumulates in ER during infection and this localization is indispensable for its function, suggesting M1 acts from the ER. We found that M1 protein selectively induces the chaperon-producing pathways (IRE1, ATF6) while, interestingly, sparing the translation-blocking arm (PERK). We identified, for the first time, a viral factor capable of selectively intervening the initiation of ER stress signaling to induce chaperon production. This finding provides a unique opportunity of using viral protein as a tool to define the activation mechanisms of individual UPR pathways.",2015 Nov 30,"['Feng, Jiaying', 'Gong, Danyang', 'Fu, Xudong', 'Wu, Ting-ting', 'Wang, Jane', 'Chang, Jennifer', 'Zhou, Jingting', 'Lu, Gang', 'Wang, Yibin', 'Sun, Ren']",Sci Rep,,,True
102bc38cfa807c84917545044b9738c285c196df,PMC,Survey and Visual Detection of Zaire ebolavirus in Clinical Samples Targeting the Nucleoprotein Gene in Sierra Leone,http://dx.doi.org/10.3389/fmicb.2015.01332,PMC4664619,26648918,CC BY,"Ebola virus (EBOV) can lead to severe hemorrhagic fever with a high risk of death in humans and other primates. To guide treatment and prevent spread of the viral infection, a rapid and sensitive detection method is required for clinical samples. Here, we described and evaluated a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method to detect Zaire ebolavirus using the nucleoprotein gene (NP) as a target sequence. Two different techniques were used, a calcein/Mn(2+) complex chromogenic method and real-time turbidity monitoring. The RT-LAMP assay detected the NP target sequence with a limit of 4.56 copies/μL within 45 min under 61°C, a similar even or increase in sensitivity than that of real-time reverse transcription-polymerase chain reaction (RT-PCR). Additionally, all pseudoviral particles or non- Zaire EBOV genomes were negative for LAMP detection, indicating that the assay was highly specific for EBOV. To appraise the availability of the RT-LAMP method for use in clinical diagnosis of EBOV, of 417 blood or swab samples collected from patients with clinically suspected infections in Sierra Leone, 307 were identified for RT-LAMP-based surveillance of EBOV. Therefore, the highly specific and sensitive RT-LAMP method allows the rapid detection of EBOV, and is a suitable tool for clinical screening, diagnosis, and primary quarantine purposes.",2015 Dec 1,"['Li, Huan', 'Wang, Xuesong', 'Liu, Wei', 'Wei, Xiao', 'Lin, Weishi', 'Li, Erna', 'Li, Puyuan', 'Dong, Derong', 'Cui, Lifei', 'Hu, Xuan', 'Li, Boxing', 'Ma, Yanyan', 'Zhao, Xiangna', 'Liu, Chao', 'Yuan, Jing']",Front Microbiol,,,False
89686b2cea177c64849d62d6224cf976e300abd0,PMC,Survey and Visual Detection of Zaire ebolavirus in Clinical Samples Targeting the Nucleoprotein Gene in Sierra Leone,http://dx.doi.org/10.3389/fmicb.2015.01332,PMC4664619,26648918,CC BY,"Ebola virus (EBOV) can lead to severe hemorrhagic fever with a high risk of death in humans and other primates. To guide treatment and prevent spread of the viral infection, a rapid and sensitive detection method is required for clinical samples. Here, we described and evaluated a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method to detect Zaire ebolavirus using the nucleoprotein gene (NP) as a target sequence. Two different techniques were used, a calcein/Mn(2+) complex chromogenic method and real-time turbidity monitoring. The RT-LAMP assay detected the NP target sequence with a limit of 4.56 copies/μL within 45 min under 61°C, a similar even or increase in sensitivity than that of real-time reverse transcription-polymerase chain reaction (RT-PCR). Additionally, all pseudoviral particles or non- Zaire EBOV genomes were negative for LAMP detection, indicating that the assay was highly specific for EBOV. To appraise the availability of the RT-LAMP method for use in clinical diagnosis of EBOV, of 417 blood or swab samples collected from patients with clinically suspected infections in Sierra Leone, 307 were identified for RT-LAMP-based surveillance of EBOV. Therefore, the highly specific and sensitive RT-LAMP method allows the rapid detection of EBOV, and is a suitable tool for clinical screening, diagnosis, and primary quarantine purposes.",2015 Dec 1,"['Li, Huan', 'Wang, Xuesong', 'Liu, Wei', 'Wei, Xiao', 'Lin, Weishi', 'Li, Erna', 'Li, Puyuan', 'Dong, Derong', 'Cui, Lifei', 'Hu, Xuan', 'Li, Boxing', 'Ma, Yanyan', 'Zhao, Xiangna', 'Liu, Chao', 'Yuan, Jing']",Front Microbiol,,,False
4ecd138ab31f520b06c5cf095657fab2685a8209,PMC,Survey and Visual Detection of Zaire ebolavirus in Clinical Samples Targeting the Nucleoprotein Gene in Sierra Leone,http://dx.doi.org/10.3389/fmicb.2015.01332,PMC4664619,26648918,CC BY,"Ebola virus (EBOV) can lead to severe hemorrhagic fever with a high risk of death in humans and other primates. To guide treatment and prevent spread of the viral infection, a rapid and sensitive detection method is required for clinical samples. Here, we described and evaluated a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method to detect Zaire ebolavirus using the nucleoprotein gene (NP) as a target sequence. Two different techniques were used, a calcein/Mn(2+) complex chromogenic method and real-time turbidity monitoring. The RT-LAMP assay detected the NP target sequence with a limit of 4.56 copies/μL within 45 min under 61°C, a similar even or increase in sensitivity than that of real-time reverse transcription-polymerase chain reaction (RT-PCR). Additionally, all pseudoviral particles or non- Zaire EBOV genomes were negative for LAMP detection, indicating that the assay was highly specific for EBOV. To appraise the availability of the RT-LAMP method for use in clinical diagnosis of EBOV, of 417 blood or swab samples collected from patients with clinically suspected infections in Sierra Leone, 307 were identified for RT-LAMP-based surveillance of EBOV. Therefore, the highly specific and sensitive RT-LAMP method allows the rapid detection of EBOV, and is a suitable tool for clinical screening, diagnosis, and primary quarantine purposes.",2015 Dec 1,"['Li, Huan', 'Wang, Xuesong', 'Liu, Wei', 'Wei, Xiao', 'Lin, Weishi', 'Li, Erna', 'Li, Puyuan', 'Dong, Derong', 'Cui, Lifei', 'Hu, Xuan', 'Li, Boxing', 'Ma, Yanyan', 'Zhao, Xiangna', 'Liu, Chao', 'Yuan, Jing']",Front Microbiol,,,True
c1eb7483446895edd38acb64e683bfd905d54211,PMC,Psoralen Inactivation of Viruses: A Process for the Safe Manipulation of Viral Antigen and Nucleic Acid,http://dx.doi.org/10.3390/v7112912,PMC4664985,26569291,CC BY,"High consequence human pathogenic viruses must be handled at biosafety level 2, 3 or 4 and must be rendered non-infectious before they can be utilized for molecular or immunological applications at lower biosafety levels. Here we evaluate psoralen-inactivated Arena-, Bunya-, Corona-, Filo-, Flavi- and Orthomyxoviruses for their suitability as antigen in immunological processes and as template for reverse transcription PCR and sequencing. The method of virus inactivation using a psoralen molecule appears to have broad applicability to RNA viruses and to leave both the particle and RNA of the treated virus intact, while rendering the virus non-infectious.",2015 Nov 12,"['Schneider, Katherine', 'Wronka-Edwards, Loni', 'Leggett-Embrey, Melissa', 'Walker, Eric', 'Sun, Peifang', 'Ondov, Brian', 'Wyman, Travis H.', 'Rosovitz, MJ', 'Bohn, Sherry S.', 'Burans, James', 'Kochel, Tadeusz']",Viruses,,,True
3359ea81b72a9d6002755539aa7f91bde5fc87bb,PMC,Fluorescent Protein Approaches in Alpha Herpesvirus Research,http://dx.doi.org/10.3390/v7112915,PMC4664988,26610544,CC BY,"In the nearly two decades since the popularization of green fluorescent protein (GFP), fluorescent protein-based methodologies have revolutionized molecular and cell biology, allowing us to literally see biological processes as never before. Naturally, this revolution has extended to virology in general, and to the study of alpha herpesviruses in particular. In this review, we provide a compendium of reported fluorescent protein fusions to herpes simplex virus 1 (HSV-1) and pseudorabies virus (PRV) structural proteins, discuss the underappreciated challenges of fluorescent protein-based approaches in the context of a replicating virus, and describe general strategies and best practices for creating new fluorescent fusions. We compare fluorescent protein methods to alternative approaches, and review two instructive examples of the caveats associated with fluorescent protein fusions, including describing several improved fluorescent capsid fusions in PRV. Finally, we present our future perspectives on the types of powerful experiments these tools now offer.",2015 Nov 19,"['Hogue, Ian B.', 'Bosse, Jens B.', 'Engel, Esteban A.', 'Scherer, Julian', 'Hu, Jiun-Ruey', 'del Rio, Tony', 'Enquist, Lynn W.']",Viruses,,,True
c75ed4c49d52ac5862313eb9d22cad197df1c138,PMC,"Novel avian single-chain fragment variable (scFv) targets dietary gluten and related natural grain prolamins, toxic entities of celiac disease",http://dx.doi.org/10.1186/s12896-015-0223-z,PMC4666168,26625857,CC BY,"BACKGROUND: Celiac disease (CD) is a chronic, small intestinal inflammatory disease mediated by dietary gluten and related prolamins. The only current therapeutic option is maintenance of a strict life-long gluten-free diet, which implies substantial burden for CD patients. Different treatment regimes might be feasible, including masking of toxic celiac peptides with blocking antibodies or fragments thereof. The objective of this study was therefore to select and produce a recombinant avian single-chain fragment variable (scFv) directed against peptic-tryptic digested gliadin (PT-Gliadin) and related celiac toxic entities. RESULTS: Gluten-free raised chicken of same age were immunized with PT-Gliadin. Chicken splenic lymphocytes, selected with antigen-coated magnetic beads, served as RNA source for the generation of cDNA. Chicken V(H) and V(L) genes were amplified from the cDNA by PCR to generate full-length scFv constructs consisting of V(H) and V(L) fragments joined by a linker sequence. ScFv constructs were ligated in a prokaryotic expression vector, which provides a C-terminal hexahistidine tag. ScFvs from several bacterial clones were expressed in soluble form and crude cell lysates screened for binding to PT-Gliadin by ELISA. We identified an enriched scFv motif, which showed reactivity to PT-Gliadin. One selected scFv candidate was expressed and purified to homogeneity. Polyclonal anti-PT-Gliadin IgY, purified from egg yolk of immunized chicken, served as control. ScFv binds in a dose-dependent manner to PT-Gliadin, comparable to IgY. Furthermore, IgY competitively displaces scFv from PT-Gliadin and natural wheat flour digest, indicating a common epitope of scFv and IgY. ScFv was tested for reactivity to different gastric digested dietary grain flours. ScFv detects common and khorasan wheat comparably with binding affinities in the high nanomolar range, while rye is detected to a lesser extent. Notably, barley and cereals which are part of the gluten-free diet, like corn and rice, are not detected by scFv. Similarly, the pseudo-grain amaranth, used as gluten-free alternative, is not targeted by scFv. This data indicate that scFv specifically recognizes toxic cereal peptides relevant in CD. CONCLUSION: ScFv can be of benefit for future CD treatment regimes.",2015 Dec 1,"['Stadlmann, Valerie', 'Harant, Hanna', 'Korschineck, Irina', 'Hermann, Marcela', 'Forster, Florian', 'Missbichler, Albert']",BMC Biotechnol,,,True
1244246ac28247b5674d6f4a8587e064bb565d7f,PMC,"Live Bird Exposure among the General Public, Guangzhou, China, May 2013",http://dx.doi.org/10.1371/journal.pone.0143582,PMC4666652,26623646,CC BY,"BACKGROUND: A novel avian-origin influenza A(H7N9) caused a major outbreak in Mainland China in early 2013. Exposure to live poultry was believed to be the major route of infection. There are limited data on how the general public changes their practices regarding live poultry exposure in response to the early outbreak of this novel influenza and the frequency of population exposure to live poultry in different areas of China. METHODOLOGY: This study investigated population exposures to live birds from various sources during the outbreak of H7N9 in Guangzhou city, China in 2013 and compared them with those observed during the 2006 influenza A(H5N1) outbreak. Adults were telephone-interviewed using two-stage sampling, stratified by three residential areas of Guangzhou: urban areas and two semi-rural areas in one of which (Zengcheng) A(H7N9) virus was detected in a chicken from wet markets. Logistic regression models were built to describe practices protecting against avian influenza, weighted by age and gender, and then compare these practices across residential areas in 2013 with those from a comparable 2006 survey. PRINCIPAL FINDINGS: Of 1196 respondents, 45% visited wet markets at least daily and 22.0% reported buying live birds from wet markets at least weekly in April-May, 2013, after the H7N9 epidemic was officially declared in late March 2013. Of those buying live birds, 32.3% reported touching birds when buying and 13.7% would slaughter the poultry at home. Although only 10.1% of the respondents reported raising backyard birds, 92.1% of those who did so had physical contact with the birds they raised. Zengcheng respondents were less likely to report buying live birds from wet markets, but more likely to buy from other sources when compared to urban respondents. Compared with the 2006 survey, the prevalence of buying live birds from wet markets, touching when buying and slaughtering birds at home had substantially declined in the 2013 survey. CONCLUSION/SIGNIFICANCE: Although population exposures to live poultry were substantially fewer in 2013 compared to 2006, wet markets and backyard poultry remained the two major sources of live bird exposures for the public in Guangzhou in 2013. Zengcheng residents seemed to have reduced buying live birds from wet markets but not from other sources in response to the detection of H7N9 virus in wet markets.",2015 Dec 1,"['Liao, Qiuyan', 'Yuan, Jun', 'Lau, Eric H. Y.', 'Chen, Guang Yan', 'Yang, Zhi Cong', 'Ma, Xiao Wei', 'Chen, Jian Dong', 'Liu, Yan Hui', 'Wang, Chang', 'Tang, Xiao Ping', 'Liu, Yu Fei', 'Zhuo, Li', 'Leung, Gabriel M.', 'Zhang, Wei', 'Cowling, Benjamin J.', 'Wang, Ming', 'Fielding, Richard']",PLoS One,,,True
f6e4ddea2e155bf319fedff2b6111ba9ee863f1e,PMC,Proteomic Analysis of the Vitreous following Experimental Retinal Detachment in Rabbits,http://dx.doi.org/10.1155/2015/583040,PMC4667062,26664739,CC BY,"Purpose. The pathogenesis of rhegmatogenous retinal detachment (RRD) remains incompletely understood, with no clinically effective treatment for potentially severe complications such as photoreceptor cell death and proliferative vitreoretinopathy. Here we investigate the protein profile of the vitreous following experimental retinal detachment using a comparative proteomic based approach. Materials and Methods. Retinal detachment was created in the right eyes of six New Zealand red pigmented rabbits. Sham surgery was undertaken in five other rabbits that were used as controls. After seven days the eyes were enucleated and the vitreous was removed. The vitreous samples were evaluated with two-dimensional polyacrylamide gel electrophoresis and the differentially expressed proteins were identified with tandem mass spectrometry. Results. Ten protein spots were found to be at least twofold differentially expressed when comparing the vitreous samples of the sham and retinal detachment surgery groups. Protein spots that were upregulated in the vitreous following retinal detachment were identified as albumin fragments, and those downregulated were found to be peroxiredoxin 2, collagen-Iα1 fragment, and α-1-antiproteinase F. Conclusions. Proteomic investigation of the rabbit vitreous has identified a set of proteins that help further our understanding of the pathogenesis of rhegmatogenous retinal detachment and its complications.",2015 Nov 18,"['Mandal, Nakul', 'Lewis, Geoffrey P.', 'Fisher, Steven K.', 'Heegaard, Steffen', 'Prause, Jan U.', 'la Cour, Morten', 'Vorum, Henrik', 'Honoré, Bent']",J Ophthalmol,,,True
dc3d3e12aa6087b1141910cf58ac7f37c8cd0793,PMC,CD11c(hi) Dendritic Cells Regulate Ly-6C(hi) Monocyte Differentiation to Preserve Immune-privileged CNS in Lethal Neuroinflammation,http://dx.doi.org/10.1038/srep17548,PMC4667186,26626303,CC BY,"Although the roles of dendritic cells (DCs) in adaptive defense have been defined well, the contribution of DCs to T cell-independent innate defense and subsequent neuroimmunopathology in immune-privileged CNS upon infection with neurotropic viruses has not been completely defined. Notably, DC roles in regulating innate CD11b(+)Ly-6C(hi) monocyte functions during neuroinflammation have not yet been addressed. Using selective ablation of CD11c(hi)PDCA-1(int/lo) DCs without alteration in CD11c(int)PDCA-1(hi) plasmacytoid DC number, we found that CD11c(hi) DCs are essential to control neuroinflammation caused by infection with neurotropic Japanese encephalitis virus, through early and increased infiltration of CD11b(+)Ly-6C(hi) monocytes and higher expression of CC chemokines. More interestingly, selective CD11c(hi) DC ablation provided altered differentiation and function of infiltrated CD11b(+)Ly-6C(hi) monocytes in the CNS through Flt3-L and GM-CSF, which was closely associated with severely enhanced neuroinflammation. Furthermore, CD11b(+)Ly-6C(hi) monocytes generated in CD11c(hi) DC-ablated environment had a deleterious rather than protective role during neuroinflammation, and were more quickly recruited into inflamed CNS, depending on CCR2, thereby exacerbating neuroinflammation via enhanced supply of virus from the periphery. Therefore, our data demonstrate that CD11c(hi) DCs provide a critical and unexpected role to preserve the immune-privileged CNS in lethal neuroinflammation via regulating the differentiation, function, and trafficking of CD11b(+)Ly-6C(hi) monocytes.",2015 Dec 2,"['Kim, Jin Hyoung', 'Choi, Jin Young', 'Kim, Seong Bum', 'Uyangaa, Erdenebelig', 'Patil, Ajit Mahadev', 'Han, Young Woo', 'Park, Sang-Youel', 'Lee, John Hwa', 'Kim, Koanhoi', 'Eo, Seong Kug']",Sci Rep,,,True
0ef13a3b7b9def8cb24c319c24e368ace22ccb0c,PMC,CD11c(hi) Dendritic Cells Regulate Ly-6C(hi) Monocyte Differentiation to Preserve Immune-privileged CNS in Lethal Neuroinflammation,http://dx.doi.org/10.1038/srep17548,PMC4667186,26626303,CC BY,"Although the roles of dendritic cells (DCs) in adaptive defense have been defined well, the contribution of DCs to T cell-independent innate defense and subsequent neuroimmunopathology in immune-privileged CNS upon infection with neurotropic viruses has not been completely defined. Notably, DC roles in regulating innate CD11b(+)Ly-6C(hi) monocyte functions during neuroinflammation have not yet been addressed. Using selective ablation of CD11c(hi)PDCA-1(int/lo) DCs without alteration in CD11c(int)PDCA-1(hi) plasmacytoid DC number, we found that CD11c(hi) DCs are essential to control neuroinflammation caused by infection with neurotropic Japanese encephalitis virus, through early and increased infiltration of CD11b(+)Ly-6C(hi) monocytes and higher expression of CC chemokines. More interestingly, selective CD11c(hi) DC ablation provided altered differentiation and function of infiltrated CD11b(+)Ly-6C(hi) monocytes in the CNS through Flt3-L and GM-CSF, which was closely associated with severely enhanced neuroinflammation. Furthermore, CD11b(+)Ly-6C(hi) monocytes generated in CD11c(hi) DC-ablated environment had a deleterious rather than protective role during neuroinflammation, and were more quickly recruited into inflamed CNS, depending on CCR2, thereby exacerbating neuroinflammation via enhanced supply of virus from the periphery. Therefore, our data demonstrate that CD11c(hi) DCs provide a critical and unexpected role to preserve the immune-privileged CNS in lethal neuroinflammation via regulating the differentiation, function, and trafficking of CD11b(+)Ly-6C(hi) monocytes.",2015 Dec 2,"['Kim, Jin Hyoung', 'Choi, Jin Young', 'Kim, Seong Bum', 'Uyangaa, Erdenebelig', 'Patil, Ajit Mahadev', 'Han, Young Woo', 'Park, Sang-Youel', 'Lee, John Hwa', 'Kim, Koanhoi', 'Eo, Seong Kug']",Sci Rep,,,False
6c982280e9ca5251ee74d0f2b84489a63a68c5bb,PMC,Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity,http://dx.doi.org/10.1038/srep17577,PMC4667252,26627732,CC BY,"Influenza virus (IFV) infection is a common cause of severe viral pneumonia associated with acute respiratory distress syndrome (ARDS), which is difficult to control with general immunosuppressive therapy including corticosteroids due to the unfavorable effect on viral replication. Studies have suggested that the excessive activation of the innate immunity by IFV is responsible for severe pathologies. In this study, we focused on CARD9, a signaling adaptor known to regulate innate immune activation through multiple innate sensor proteins, and investigated its role in anti-IFV defense and lung pathogenesis in a mouse model recapitulating severe influenza pneumonia with ARDS. We found that influenza pneumonia was dramatically attenuated in Card9-deficient mice, which showed improved mortality with reduced inflammatory cytokines and chemokines in the infected lungs. However, viral clearance, type-I interferon production, and the development of anti-viral B and T cell immunity were not compromised by CARD9 deficiency. Syk or CARD9-deficient DCs but not macrophages showed impaired cytokine but not type-I interferon production in response to IFV in vitro, indicating a possible role for the Syk-CARD9 pathway in DCs in excessive inflammation of IFV-infected lungs. Therefore, inhibition of this pathway is an ideal therapeutic target for severe influenza pneumonia without affecting viral clearance.",2015 Dec 2,"['Uematsu, Takayuki', 'Iizasa, Ei’ichi', 'Kobayashi, Noritada', 'Yoshida, Hiroki', 'Hara, Hiromitsu']",Sci Rep,,,True
5985c7d31f6f88ce569f9a44759a14e50fad41ac,PMC,Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity,http://dx.doi.org/10.1038/srep17577,PMC4667252,26627732,CC BY,"Influenza virus (IFV) infection is a common cause of severe viral pneumonia associated with acute respiratory distress syndrome (ARDS), which is difficult to control with general immunosuppressive therapy including corticosteroids due to the unfavorable effect on viral replication. Studies have suggested that the excessive activation of the innate immunity by IFV is responsible for severe pathologies. In this study, we focused on CARD9, a signaling adaptor known to regulate innate immune activation through multiple innate sensor proteins, and investigated its role in anti-IFV defense and lung pathogenesis in a mouse model recapitulating severe influenza pneumonia with ARDS. We found that influenza pneumonia was dramatically attenuated in Card9-deficient mice, which showed improved mortality with reduced inflammatory cytokines and chemokines in the infected lungs. However, viral clearance, type-I interferon production, and the development of anti-viral B and T cell immunity were not compromised by CARD9 deficiency. Syk or CARD9-deficient DCs but not macrophages showed impaired cytokine but not type-I interferon production in response to IFV in vitro, indicating a possible role for the Syk-CARD9 pathway in DCs in excessive inflammation of IFV-infected lungs. Therefore, inhibition of this pathway is an ideal therapeutic target for severe influenza pneumonia without affecting viral clearance.",2015 Dec 2,"['Uematsu, Takayuki', 'Iizasa, Ei’ichi', 'Kobayashi, Noritada', 'Yoshida, Hiroki', 'Hara, Hiromitsu']",Sci Rep,,,False
c280d46d6fa7e2c2938a5c09bd6b092e1058a9b0,PMC,Protection against Foot-and-Mouth Disease Virus in Guinea Pigs via Oral Administration of Recombinant Lactobacillus plantarum Expressing VP1,http://dx.doi.org/10.1371/journal.pone.0143750,PMC4667879,26629822,CC BY,"Mucosal vaccination is an effective strategy for generating antigen-specific immune responses against mucosal infections of foot-and-mouth disease virus (FMDV). In this study, Lactobacillus plantarum strains NC8 and WCFS1 were used as oral delivery vehicles containing a pSIP411-VP1 recombinant plasmid to initiate mucosal and systemic immune responses in guinea pigs. Guinea pigs were orally vaccinated (three doses) with NC8-pSIP411, NC8-pSIP411-VP1, WCFS1-pSIP411, WCFS1-pSIP411-VP1 or milk. Animals immunized with NC8-pSIP411-VP1 and WCFS1-pSIP411-VP1 developed high levels of antigen-specific serum IgG, IgA, IgM, mucosal secretory IgA (sIgA) and neutralizing antibodies, and revealed stronger cell-mediated immune responses and enhanced protection against FMDV challenge compared with control groups. The recombinant pSIP411-VP1 effectively improved immunoprotection against FMDV in guinea pigs.",2015 Dec 2,"['Wang, Miao', 'Pan, Li', 'Zhou, Peng', 'Lv, Jianliang', 'Zhang, Zhongwang', 'Wang, Yonglu', 'Zhang, Yongguang']",PLoS One,,,True
8fddf78a6b3a823c0ebeb2dfbfe274e46fee97f3,PMC,Brain Meta-Transcriptomics from Harbor Seals to Infer the Role of the Microbiome and Virome in a Stranding Event,http://dx.doi.org/10.1371/journal.pone.0143944,PMC4668051,26630132,CC BY,"Marine diseases are becoming more frequent, and tools for identifying pathogens and disease reservoirs are needed to help prevent and mitigate epizootics. Meta-transcriptomics provides insights into disease etiology by cataloguing and comparing sequences from suspected pathogens. This method is a powerful approach to simultaneously evaluate both the viral and bacterial communities, but few studies have applied this technique in marine systems. In 2009 seven harbor seals, Phoca vitulina, stranded along the California coast from a similar brain disease of unknown cause of death (UCD). We evaluated the differences between the virome and microbiome of UCDs and harbor seals with known causes of death. Here we determined that UCD stranded animals had no viruses in their brain tissue. However, in the bacterial community, we identified Burkholderia and Coxiella burnetii as important pathogens associated with this stranding event. Burkholderia were 100% prevalent and ~2.8 log2 fold more abundant in the UCD animals. Further, while C. burnetii was found in only 35.7% of all samples, it was highly abundant (~94% of the total microbial community) in a single individual. In this harbor seal, C. burnetii showed high transcription rates of invading and translation genes, implicating it in the pathogenesis of this animal. Based on these data we propose that Burkholderia taxa and C. burnetii are potentially important opportunistic neurotropic pathogens in UCD stranded harbor seals.",2015 Dec 2,"['Rosales, Stephanie M.', 'Vega Thurber, Rebecca']",PLoS One,,,True
8055b4c692a2717a904b71e948926aaf953896e5,PMC,US-like isolates of porcine epidemic diarrhea virus from Japanese outbreaks between 2013 and 2014,http://dx.doi.org/10.1186/s40064-015-1552-z,PMC4668244,26693114,CC BY,"Since late 2013, outbreaks of porcine epidemic diarrhea virus (PEDV) have reemerged in Japan. In the present study, we observed a high detection rate of PEDV, with 72.5 % (148/204) of diarrhea samples (suckling, weaned, and sows) and 88.5 % (77/87) of farms experiencing acute diarrhea found to be positive for PEDV by reverse transcription PCR. Sequencing and phylogenic analyses of the partial spike gene and ORF3 of PEDV demonstrated that all prevailing Japanese PEDV isolates belonged to novel genotypes that differed from previously reported strains and the two PEDV vaccine strains currently being used in Japan. Sequence and phylogenetic analysis revealed prevailing PEDV isolates in Japan had the greatest genetic similarity to US isolates and were not vaccine-related. Unlike vaccine strains, all prevailing field PEDV isolates in Japan were found to have a number of amino acid differences in the neutralizing epitope domain, COE, which may affect antigenicity and vaccine efficacy. The present study indicates recent PEDV isolates may have been introduced into Japan from overseas and highlights the urgent requirement of novel vaccines for controlling PEDV outbreaks in Japan.",2015 Dec 2,"['Van Diep, Nguyen', 'Norimine, Junzo', 'Sueyoshi, Masuo', 'Lan, Nguyen Thi', 'Hirai, Takuya', 'Yamaguchi, Ryoji']",Springerplus,,,True
44f82307e441f32a4ddd4ea51a8f823c593e2151,PMC,Glycyrrhizic Acid Promotes M1 Macrophage Polarization in Murine Bone Marrow-Derived Macrophages Associated with the Activation of JNK and NF-κB,http://dx.doi.org/10.1155/2015/372931,PMC4668314,26664149,CC BY,"The roots and rhizomes of Glycyrrhiza species (licorice) have been widely used as natural sweeteners and herbal medicines. The aim of this study is to investigate the effect of glycyrrhizic acid (GA) from licorice on macrophage polarization. Both phenotypic and functional activities of murine bone marrow-derived macrophages (BMDMs) treated by GA were assessed. Our results showed that GA obviously increased the cell surface expression of CD80, CD86, and MHCII molecules. Meanwhile, GA upregulated the expression of CCR7 and the production of TNF-α, IL-12, IL-6, and NO (the markers of classically activated (M1) macrophages), whereas it downregulated the expression of MR, Ym1, and Arg1 (the markers of alternatively activated (M2) macrophage). The functional tests showed that GA dramatically enhanced the uptake of FITC-dextran and E. coli K88 by BMDMs and decreased the intracellular survival of E. coli K88 and S. typhimurium. Moreover, we demonstrated that JNK and NF-κB activation are required for GA-induced NO and M1-related cytokines production, while ERK1/2 pathway exhibits a regulatory effect via induction of IL-10. Together, these findings indicated that GA promoted polarization of M1 macrophages and enhanced its phagocytosis and bactericidal capacity. The results expanded our knowledge about the role of GA in macrophage polarization.",2015 Nov 19,"['Mao, Yulong', 'Wang, Baikui', 'Xu, Xin', 'Du, Wei', 'Li, Weifen', 'Wang, Youming']",Mediators Inflamm,,,True
4e6d4c7d205f8a78c8b6adf1e0a27a23254851d7,PMC,Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets,http://dx.doi.org/10.1038/srep17554,PMC4668369,26631542,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel and highly pathogenic human coronavirus and has quickly spread to other countries in the Middle East, Europe, North Africa and Asia since 2012. Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε, and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. Further analysis showed that ORF4b could also inhibit IRF3 and IRF7-induced production of IFN-β, whereas deletion of the nuclear localization signal of ORF4b abrogated its ability to inhibit IRF3 and IRF7-induced production of IFN-β, but not IFN-β production induced by RIG-I, MDA5, MAVS, IKKε, and TBK-1, suggesting that ORF4b could inhibit the induction of IFN-β in both the cytoplasm and nucleus. Collectively, these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm, and also in the nucleus with unknown mechanism. Viruses have evolved multiple strategies to evade or thwart a host’s antiviral responses. A novel human coronavirus (HCoV), Middle East respiratory syndrome coronavirus (MERS-CoV), is distinguished from other coronaviruses by its high pathogenicity and mortality. However, virulence determinants that distinguish MERS-CoV from other HCoVs have yet to be identified. MERS-CoV ORF4b antagonizes the early antiviral response, which may contribute to MERS-CoV pathogenesis. Here, we report the identification of the interferon (IFN) antagonism mechanism of MERS-CoV ORF4b. MERS-CoV ORF4b inhibits the production of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm, and also in the nucleus with unknown mechanism. These findings provide a rationale for the novel pathogenesis of MERS-CoV as well as a basis for developing a candidate therapeutic against this virus.",2015 Dec 3,"['Yang, Yang', 'Ye, Fei', 'Zhu, Na', 'Wang, Wenling', 'Deng, Yao', 'Zhao, Zhengdong', 'Tan, Wenjie']",Sci Rep,,,True
aa7340d432336723e1ffd475cd2940170b33995c,PMC,Aetiology-Specific Estimates of the Global and Regional Incidence and Mortality of Diarrhoeal Diseases Commonly Transmitted through Food,http://dx.doi.org/10.1371/journal.pone.0142927,PMC4668836,26632843,CC BY,"BACKGROUND: Diarrhoeal diseases are major contributors to the global burden of disease, particularly in children. However, comprehensive estimates of the incidence and mortality due to specific aetiologies of diarrhoeal diseases are not available. The objective of this study is to provide estimates of the global and regional incidence and mortality of diarrhoeal diseases caused by nine pathogens that are commonly transmitted through foods. METHODS AND FINDINGS: We abstracted data from systematic reviews and, depending on the overall mortality rates of the country, applied either a national incidence estimate approach or a modified Child Health Epidemiology Reference Group (CHERG) approach to estimate the aetiology-specific incidence and mortality of diarrhoeal diseases, by age and region. The nine diarrhoeal diseases assessed caused an estimated 1.8 billion (95% uncertainty interval [UI] 1.1–3.3 billion) cases and 599,000 (95% UI 472,000–802,000) deaths worldwide in 2010. The largest number of cases were caused by norovirus (677 million; 95% UI 468–1,153 million), enterotoxigenic Escherichia coli (ETEC) (233 million; 95% UI 154–380 million), Shigella spp. (188 million; 95% UI 94–379 million) and Giardia lamblia (179 million; 95% UI 125–263); the largest number of deaths were caused by norovirus (213,515; 95% UI 171,783–266,561), enteropathogenic E. coli (121,455; 95% UI 103,657–143,348), ETEC (73,041; 95% UI 55,474–96,984) and Shigella (64,993; 95% UI 48,966–92,357). There were marked regional differences in incidence and mortality for these nine diseases. Nearly 40% of cases and 43% of deaths caused by these nine diarrhoeal diseases occurred in children under five years of age. CONCLUSIONS: Diarrhoeal diseases caused by these nine pathogens are responsible for a large disease burden, particularly in children. These aetiology-specific burden estimates can inform efforts to reduce diarrhoeal diseases caused by these nine pathogens commonly transmitted through foods.",2015 Dec 3,"['Pires, Sara M.', 'Fischer-Walker, Christa L.', 'Lanata, Claudio F.', 'Devleesschauwer, Brecht', 'Hall, Aron J.', 'Kirk, Martyn D.', 'Duarte, Ana S. R.', 'Black, Robert E.', 'Angulo, Frederick J.']",PLoS One,,,True
97958d7950411acf70fa08f764cac6dabe0963a8,PMC,Aetiology-Specific Estimates of the Global and Regional Incidence and Mortality of Diarrhoeal Diseases Commonly Transmitted through Food,http://dx.doi.org/10.1371/journal.pone.0142927,PMC4668836,26632843,CC BY,"BACKGROUND: Diarrhoeal diseases are major contributors to the global burden of disease, particularly in children. However, comprehensive estimates of the incidence and mortality due to specific aetiologies of diarrhoeal diseases are not available. The objective of this study is to provide estimates of the global and regional incidence and mortality of diarrhoeal diseases caused by nine pathogens that are commonly transmitted through foods. METHODS AND FINDINGS: We abstracted data from systematic reviews and, depending on the overall mortality rates of the country, applied either a national incidence estimate approach or a modified Child Health Epidemiology Reference Group (CHERG) approach to estimate the aetiology-specific incidence and mortality of diarrhoeal diseases, by age and region. The nine diarrhoeal diseases assessed caused an estimated 1.8 billion (95% uncertainty interval [UI] 1.1–3.3 billion) cases and 599,000 (95% UI 472,000–802,000) deaths worldwide in 2010. The largest number of cases were caused by norovirus (677 million; 95% UI 468–1,153 million), enterotoxigenic Escherichia coli (ETEC) (233 million; 95% UI 154–380 million), Shigella spp. (188 million; 95% UI 94–379 million) and Giardia lamblia (179 million; 95% UI 125–263); the largest number of deaths were caused by norovirus (213,515; 95% UI 171,783–266,561), enteropathogenic E. coli (121,455; 95% UI 103,657–143,348), ETEC (73,041; 95% UI 55,474–96,984) and Shigella (64,993; 95% UI 48,966–92,357). There were marked regional differences in incidence and mortality for these nine diseases. Nearly 40% of cases and 43% of deaths caused by these nine diarrhoeal diseases occurred in children under five years of age. CONCLUSIONS: Diarrhoeal diseases caused by these nine pathogens are responsible for a large disease burden, particularly in children. These aetiology-specific burden estimates can inform efforts to reduce diarrhoeal diseases caused by these nine pathogens commonly transmitted through foods.",2015 Dec 3,"['Pires, Sara M.', 'Fischer-Walker, Christa L.', 'Lanata, Claudio F.', 'Devleesschauwer, Brecht', 'Hall, Aron J.', 'Kirk, Martyn D.', 'Duarte, Ana S. R.', 'Black, Robert E.', 'Angulo, Frederick J.']",PLoS One,,,False
cf5227d38a667f9612804971951c05e55d9bda01,PMC,Identification of Peptide Inhibitors of Enveloped Viruses Using Support Vector Machine,http://dx.doi.org/10.1371/journal.pone.0144171,PMC4670226,26636321,CC BY,"The peptides derived from envelope proteins have been shown to inhibit the protein-protein interactions in the virus membrane fusion process and thus have a great potential to be developed into effective antiviral therapies. There are three types of envelope proteins each exhibiting distinct structure folds. Although the exact fusion mechanism remains elusive, it was suggested that the three classes of viral fusion proteins share a similar mechanism of membrane fusion. The common mechanism of action makes it possible to correlate the properties of self-derived peptide inhibitors with their activities. Here we developed a support vector machine model using sequence-based statistical scores of self-derived peptide inhibitors as input features to correlate with their activities. The model displayed 92% prediction accuracy with the Matthew’s correlation coefficient of 0.84, obviously superior to those using physicochemical properties and amino acid decomposition as input. The predictive support vector machine model for self- derived peptides of envelope proteins would be useful in development of antiviral peptide inhibitors targeting the virus fusion process.",2015 Dec 4,"['Xu, Yongtao', 'Yu, Shui', 'Zou, Jian-Wei', 'Hu, Guixiang', 'Rahman, Noorsaadah A. B. D.', 'Othman, Rozana Binti', 'Tao, Xia', 'Huang, Meilan']",PLoS One,,,True
2a6a9de82dc0494f32530e1ee8ee7509367a04fd,PMC,Building International Genomics Collaboration for Global Health Security,http://dx.doi.org/10.3389/fpubh.2015.00264,PMC4670856,26697418,CC BY,"Genome science and technologies are transforming life sciences globally in many ways and becoming a highly desirable area for international collaboration to strengthen global health. The Genome Science Program at the Los Alamos National Laboratory is leveraging a long history of expertise in genomics research to assist multiple partner nations in advancing their genomics and bioinformatics capabilities. The capability development objectives focus on providing a molecular genomics-based scientific approach for pathogen detection, characterization, and biosurveillance applications. The general approaches include introduction of basic principles in genomics technologies, training on laboratory methodologies and bioinformatic analysis of resulting data, procurement, and installation of next-generation sequencing instruments, establishing bioinformatics software capabilities, and exploring collaborative applications of the genomics capabilities in public health. Genome centers have been established with public health and research institutions in the Republic of Georgia, Kingdom of Jordan, Uganda, and Gabon; broader collaborations in genomics applications have also been developed with research institutions in many other countries.",2015 Dec 7,"['Cui, Helen H.', 'Erkkila, Tracy', 'Chain, Patrick S. G.', 'Vuyisich, Momchilo']",Front Public Health,,,True
a138ff680ae9e158019717356e8fcab523e7cad2,PMC,Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0144475,PMC4671582,26641892,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) with pandemic potential is a major worldwide threat to public health. However, vaccine development for this pathogen lags behind as immunity associated with protection is currently largely unknown. In this study, an immunoinformatics-driven genome-wide screening strategy of vaccine targets was performed to thoroughly screen the vital and effective dominant immunogens against MERS-CoV. Conservancy and population coverage analysis of the epitopes were done by the Immune Epitope Database. The results showed that the nucleocapsid (N) protein of MERS-CoV might be a better protective immunogen with high conservancy and potential eliciting both neutralizing antibodies and T-cell responses compared with spike (S) protein. Further, the B-cell, helper T-cell and cytotoxic T lymphocyte (CTL) epitopes were screened and mapped to the N protein. A total of 15 linear and 10 conformal B-cell epitopes that may induce protective neutralizing antibodies were obtained. Additionally, a total of 71 peptides with 9-mer core sequence were identified as helper T-cell epitopes, and 34 peptides were identified as CTL epitopes. Based on the maximum HLA binding alleles, top 10 helper T-cell epitopes and CTL epitopes that may elicit protective cellular immune responses against MERS-CoV were selected as MERS vaccine candidates. Population coverage analysis showed that the putative helper T-cell epitopes and CTL epitopes could cover the vast majority of the population in 15 geographic regions considered where vaccine would be employed. The B- and T-cell stimulation potentials of the screened epitopes is to be further validated for their efficient use as vaccines against MERS-CoV. Collectively, this study provides novel vaccine target candidates and may prompt further development of vaccines against MERS-CoV and other emerging infectious diseases.",2015 Dec 7,"['Shi, Jiandong', 'Zhang, Jing', 'Li, Sijin', 'Sun, Jing', 'Teng, Yumei', 'Wu, Meini', 'Li, Jianfan', 'Li, Yanhan', 'Hu, Ningzhu', 'Wang, Haixuan', 'Hu, Yunzhang']",PLoS One,,,True
06d3c7caaf09a3ae5204d955b0036aca10c6634a,PMC,Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0144475,PMC4671582,26641892,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) with pandemic potential is a major worldwide threat to public health. However, vaccine development for this pathogen lags behind as immunity associated with protection is currently largely unknown. In this study, an immunoinformatics-driven genome-wide screening strategy of vaccine targets was performed to thoroughly screen the vital and effective dominant immunogens against MERS-CoV. Conservancy and population coverage analysis of the epitopes were done by the Immune Epitope Database. The results showed that the nucleocapsid (N) protein of MERS-CoV might be a better protective immunogen with high conservancy and potential eliciting both neutralizing antibodies and T-cell responses compared with spike (S) protein. Further, the B-cell, helper T-cell and cytotoxic T lymphocyte (CTL) epitopes were screened and mapped to the N protein. A total of 15 linear and 10 conformal B-cell epitopes that may induce protective neutralizing antibodies were obtained. Additionally, a total of 71 peptides with 9-mer core sequence were identified as helper T-cell epitopes, and 34 peptides were identified as CTL epitopes. Based on the maximum HLA binding alleles, top 10 helper T-cell epitopes and CTL epitopes that may elicit protective cellular immune responses against MERS-CoV were selected as MERS vaccine candidates. Population coverage analysis showed that the putative helper T-cell epitopes and CTL epitopes could cover the vast majority of the population in 15 geographic regions considered where vaccine would be employed. The B- and T-cell stimulation potentials of the screened epitopes is to be further validated for their efficient use as vaccines against MERS-CoV. Collectively, this study provides novel vaccine target candidates and may prompt further development of vaccines against MERS-CoV and other emerging infectious diseases.",2015 Dec 7,"['Shi, Jiandong', 'Zhang, Jing', 'Li, Sijin', 'Sun, Jing', 'Teng, Yumei', 'Wu, Meini', 'Li, Jianfan', 'Li, Yanhan', 'Hu, Ningzhu', 'Wang, Haixuan', 'Hu, Yunzhang']",PLoS One,,,False
fff6f848d352c486049ec8046bc44e900fefb2e3,PMC,Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0144475,PMC4671582,26641892,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) with pandemic potential is a major worldwide threat to public health. However, vaccine development for this pathogen lags behind as immunity associated with protection is currently largely unknown. In this study, an immunoinformatics-driven genome-wide screening strategy of vaccine targets was performed to thoroughly screen the vital and effective dominant immunogens against MERS-CoV. Conservancy and population coverage analysis of the epitopes were done by the Immune Epitope Database. The results showed that the nucleocapsid (N) protein of MERS-CoV might be a better protective immunogen with high conservancy and potential eliciting both neutralizing antibodies and T-cell responses compared with spike (S) protein. Further, the B-cell, helper T-cell and cytotoxic T lymphocyte (CTL) epitopes were screened and mapped to the N protein. A total of 15 linear and 10 conformal B-cell epitopes that may induce protective neutralizing antibodies were obtained. Additionally, a total of 71 peptides with 9-mer core sequence were identified as helper T-cell epitopes, and 34 peptides were identified as CTL epitopes. Based on the maximum HLA binding alleles, top 10 helper T-cell epitopes and CTL epitopes that may elicit protective cellular immune responses against MERS-CoV were selected as MERS vaccine candidates. Population coverage analysis showed that the putative helper T-cell epitopes and CTL epitopes could cover the vast majority of the population in 15 geographic regions considered where vaccine would be employed. The B- and T-cell stimulation potentials of the screened epitopes is to be further validated for their efficient use as vaccines against MERS-CoV. Collectively, this study provides novel vaccine target candidates and may prompt further development of vaccines against MERS-CoV and other emerging infectious diseases.",2015 Dec 7,"['Shi, Jiandong', 'Zhang, Jing', 'Li, Sijin', 'Sun, Jing', 'Teng, Yumei', 'Wu, Meini', 'Li, Jianfan', 'Li, Yanhan', 'Hu, Ningzhu', 'Wang, Haixuan', 'Hu, Yunzhang']",PLoS One,,,False
7c31dec4fa9159b171d8e08d603ad0535a379d39,PMC,Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0144475,PMC4671582,26641892,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) with pandemic potential is a major worldwide threat to public health. However, vaccine development for this pathogen lags behind as immunity associated with protection is currently largely unknown. In this study, an immunoinformatics-driven genome-wide screening strategy of vaccine targets was performed to thoroughly screen the vital and effective dominant immunogens against MERS-CoV. Conservancy and population coverage analysis of the epitopes were done by the Immune Epitope Database. The results showed that the nucleocapsid (N) protein of MERS-CoV might be a better protective immunogen with high conservancy and potential eliciting both neutralizing antibodies and T-cell responses compared with spike (S) protein. Further, the B-cell, helper T-cell and cytotoxic T lymphocyte (CTL) epitopes were screened and mapped to the N protein. A total of 15 linear and 10 conformal B-cell epitopes that may induce protective neutralizing antibodies were obtained. Additionally, a total of 71 peptides with 9-mer core sequence were identified as helper T-cell epitopes, and 34 peptides were identified as CTL epitopes. Based on the maximum HLA binding alleles, top 10 helper T-cell epitopes and CTL epitopes that may elicit protective cellular immune responses against MERS-CoV were selected as MERS vaccine candidates. Population coverage analysis showed that the putative helper T-cell epitopes and CTL epitopes could cover the vast majority of the population in 15 geographic regions considered where vaccine would be employed. The B- and T-cell stimulation potentials of the screened epitopes is to be further validated for their efficient use as vaccines against MERS-CoV. Collectively, this study provides novel vaccine target candidates and may prompt further development of vaccines against MERS-CoV and other emerging infectious diseases.",2015 Dec 7,"['Shi, Jiandong', 'Zhang, Jing', 'Li, Sijin', 'Sun, Jing', 'Teng, Yumei', 'Wu, Meini', 'Li, Jianfan', 'Li, Yanhan', 'Hu, Ningzhu', 'Wang, Haixuan', 'Hu, Yunzhang']",PLoS One,,,False
cd9b28a218d57ae7506637d96b2a396dca870e0f,PMC,"The Burden of Influenza-Associated Hospitalizations in Oman, January 2008-June 2013",http://dx.doi.org/10.1371/journal.pone.0144186,PMC4671710,26642055,CC0,"INTRODUCTION: Acute respiratory infections (ARI), including influenza, comprise a leading cause of morbidity and mortality worldwide. Influenza surveillance provides important information to inform policy on influenza control and vaccination. While the epidemiology of influenza has been well characterized in western countries, few data exist on influenza epidemiology in the Eastern Mediterranean Region. We describe the epidemiology of influenza virus in Oman. METHODS: Using syndromic case definitions and protocols, patients from four regional hospitals in Oman were enrolled in a descriptive prospective study to characterize the burden of severe acute respiratory infections (SARI) and influenza. Eligible patients provided demographic information as well as oropharyngeal (OP) and nasopharyngeal (NP) swabs. Specimens were tested for influenza A and influenza B; influenza A viruses were subtyped using RT-PCR. RESULTS: From January 2008 through June 2013, a total of 5,147 cases were enrolled and tested for influenza. Influenza strains were detected in 8% of cases for whom samples were available. Annual incidence rates ranged from 0.5 to 15.4 cases of influenza-associated SARI per 100,000 population. The median age of influenza patients was 6 years with children 0–2 years accounting for 34% of all influenza-associated hospitalizations. By contrast, the median age of non-influenza SARI cases was 1 year with children 0–2 years comprising 59% of SARI. Compared to non-influenza SARI cases, a greater proportion of influenza cases had pre-existing chronic conditions and underwent ventilation during hospitalization. CONCLUSIONS: Influenza virus is associated with a substantial proportion of SARI in Oman. Influenza in Oman approximately follows northern hemisphere seasonality, with major peaks in October to December and a lesser peak around April. The burden of influenza was greatest in children and the elderly. Future efforts should examine the burden of influenza in other potential risk groups such as pregnant women to inform interventions including targeted vaccination.",2015 Dec 7,"['Al-Awaidy, Salah', 'Hamid, Sarah', 'Al Obaidani, Idris', 'Al Baqlani, Said', 'Al Busaidi, Suleiman', 'Bawikar, Shyam', 'El-Shoubary, Waleed', 'Dueger, Erica L.', 'Said, Mayar M.', 'Elamin, Emdeldin', 'Shah, Parag', 'Talaat, Maha']",PLoS One,,,True
ff9d9713206da30022af4f9095058368eeb1f3f8,PMC,"A New Decade of Veterinary Research: Societal Relevance, Global Collaboration, and Translational Medicine",http://dx.doi.org/10.3389/fvets.2015.00001,PMC4672166,26664930,CC BY,,2015 Feb 26,"Christopher, Mary M.",Front Vet Sci,,,True
ac9e71b8ce45ac71f25abec56e4d60db6b68d703,PMC,Salmonella enterica Serovars Enteritidis Infection Alters the Indigenous Microbiota Diversity in Young Layer Chicks,http://dx.doi.org/10.3389/fvets.2015.00061,PMC4672283,26664988,CC BY,"Avian gastrointestinal (GI) tracts are highly populated with a diverse array of microorganisms that share a symbiotic relationship with their hosts and contribute to the overall health and disease state of the intestinal tract. The microbiome of the young chick is easily prone to alteration in its composition by both exogenous and endogenous factors, especially during the early posthatch period. The genetic background of the host and exposure to pathogens can impact the diversity of the microbial profile that consequently contributes to the disease progression in the host. The objective of this study was to profile the composition and structure of the gut microbiota in young chickens from two genetically distinct highly inbred lines. Furthermore, the effect of the Salmonella Enteritidis infection on altering the composition makeup of the chicken microbiome was evaluated through the 16S rRNA gene sequencing analysis. One-day-old layer chicks were challenged with S. Enteritidis and the host cecal microbiota profile as well as the degree of susceptibility to Salmonella infection was examined at 2 and 7 days post infection. Our result indicated that host genotype had a limited effect on resistance to S. Enteritidis infection. Alpha diversity, beta diversity, and overall microbiota composition were analyzed for four factors: host genotype, age, treatment, and postinfection time points. S. Enteritidis infection in young chicks was found to significantly reduce the overall diversity of the microbiota population with expansion of Enterobacteriaceae family. These changes indicated that Salmonella colonization in the GI tract of the chickens has a direct effect on altering the natural development of the GI microbiota. The impact of S. Enteritidis infection on microbial communities was also more substantial in the late stage of infection. Significant inverse correlation between Enterobacteriaceae and Lachnospiraceae family in both non-infected and infected groups, suggested possible antagonistic interaction between members of these two taxa, which could potentially influences the overall microbial population in the gut. Our results also revealed that genetic difference between two lines had minimal effect on the establishment of microbiota population. Overall, this study provided preliminary insights into the contributing role of S. Enteritidis in influencing the overall makeup of chicken’s gut microbiota.",2015 Nov 23,"['Mon, Khin K. Z.', 'Saelao, Perot', 'Halstead, Michelle M.', 'Chanthavixay, Ganrea', 'Chang, Huai-Chen', 'Garas, Lydia', 'Maga, Elizabeth A.', 'Zhou, Huaijun']",Front Vet Sci,,,True
dcceda0265e3540a12eef54836297a20d890c4a8,PMC,Detection of airborne viruses using electro-aerodynamic deposition and a field-effect transistor,http://dx.doi.org/10.1038/srep17462,PMC4672335,26642822,CC BY,"We report a technique for the detection of aerosolized viruses. Conventional field-effect-transistor (FET)-based techniques use solution-based processes, thus require antibody binding to the detection region of the FET prior to the supply of the analyte. With the method described here, virus–antibody-bound particles are delivered to the FET during detection; therefore, neither a pre-treatment antibody binding step on the FET channel nor washing process for virus–antibody-binding are necessary. Our method is based on the concept that virus–antibody-bound particles are larger than the virus or antibody alone, and thus have larger charge numbers following aerosol charging. When these particles are charged by negative ions and electro-aerodynamically deposited on a substrate, there exists a location on the substrate where neither lone virus nor antibody particles land, and where only virus–antibody-bound particles are deposited. If this location coincides with the channel of the FET, the resulting variation in the current can be used to indicate the existence of a virus. By aerosolizing a mixed solution of the virus and the antibody, only the virus–antibody-bound particles were transported to the swCNT-FET, and the electric current in the swCNT-FET decreased to 30% of that measured with no deposited particles.",2015 Dec 8,"['Park, Kyu-Tae', 'Cho, Dong-Guk', 'Park, Ji-Woon', 'Hong, Seunghun', 'Hwang, Jungho']",Sci Rep,,,True
6372aae30124dd3aca4a113413b4fc1ecc19c22c,PMC,Detection of airborne viruses using electro-aerodynamic deposition and a field-effect transistor,http://dx.doi.org/10.1038/srep17462,PMC4672335,26642822,CC BY,"We report a technique for the detection of aerosolized viruses. Conventional field-effect-transistor (FET)-based techniques use solution-based processes, thus require antibody binding to the detection region of the FET prior to the supply of the analyte. With the method described here, virus–antibody-bound particles are delivered to the FET during detection; therefore, neither a pre-treatment antibody binding step on the FET channel nor washing process for virus–antibody-binding are necessary. Our method is based on the concept that virus–antibody-bound particles are larger than the virus or antibody alone, and thus have larger charge numbers following aerosol charging. When these particles are charged by negative ions and electro-aerodynamically deposited on a substrate, there exists a location on the substrate where neither lone virus nor antibody particles land, and where only virus–antibody-bound particles are deposited. If this location coincides with the channel of the FET, the resulting variation in the current can be used to indicate the existence of a virus. By aerosolizing a mixed solution of the virus and the antibody, only the virus–antibody-bound particles were transported to the swCNT-FET, and the electric current in the swCNT-FET decreased to 30% of that measured with no deposited particles.",2015 Dec 8,"['Park, Kyu-Tae', 'Cho, Dong-Guk', 'Park, Ji-Woon', 'Hong, Seunghun', 'Hwang, Jungho']",Sci Rep,,,False
c3461b2484a2c1b0532e47afba87d235e350b9e7,PMC,De novo transcriptome reconstruction and annotation of the Egyptian rousette bat,http://dx.doi.org/10.1186/s12864-015-2124-x,PMC4672546,26643810,CC BY,"BACKGROUND: The Egyptian Rousette bat (Rousettus aegyptiacus), a common fruit bat species found throughout Africa and the Middle East, was recently identified as a natural reservoir host of Marburg virus. With Ebola virus, Marburg virus is a member of the family Filoviridae that causes severe hemorrhagic fever disease in humans and nonhuman primates, but results in little to no pathological consequences in bats. Understanding host-pathogen interactions within reservoir host species and how it differs from hosts that experience severe disease is an important aspect of evaluating viral pathogenesis and developing novel therapeutics and methods of prevention. RESULTS: Progress in studying bat reservoir host responses to virus infection is hampered by the lack of host-specific reagents required for immunological studies. In order to establish a basis for the design of reagents, we sequenced, assembled, and annotated the R. aegyptiacus transcriptome. We performed de novo transcriptome assembly using deep RNA sequencing data from 11 distinct tissues from one male and one female bat. We observed high similarity between this transcriptome and those available from other bat species. Gene expression analysis demonstrated clustering of expression profiles by tissue, where we also identified enrichment of tissue-specific gene ontology terms. In addition, we identified and experimentally validated the expression of novel coding transcripts that may be specific to this species. CONCLUSION: We comprehensively characterized the R. aegyptiacus transcriptome de novo. This transcriptome will be an important resource for understanding bat immunology, physiology, disease pathogenesis, and virus transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2124-x) contains supplementary material, which is available to authorized users.",2015 Dec 7,"['Lee, Albert K.', 'Kulcsar, Kirsten A.', 'Elliott, Oliver', 'Khiabanian, Hossein', 'Nagle, Elyse R.', 'Jones, Megan E.B.', 'Amman, Brian R.', 'Sanchez-Lockhart, Mariano', 'Towner, Jonathan S.', 'Palacios, Gustavo', 'Rabadan, Raul']",BMC Genomics,,,True
9a98d242545d1ff31799bc6197ac31e3f2cd4447,PMC,Transcriptome-Wide Cleavage Site Mapping on Cellular mRNAs Reveals Features Underlying Sequence-Specific Cleavage by the Viral Ribonuclease SOX,http://dx.doi.org/10.1371/journal.ppat.1005305,PMC4672902,26646420,CC BY,"Many viruses express factors that reduce host gene expression through widespread degradation of cellular mRNA. An example of this class of proteins is the mRNA-targeting endoribonuclease SOX from the gamma-herpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV). Previous studies indicated that cleavage of messenger RNAs (mRNA) by SOX occurs at specific locations defined by the sequence of the target RNA, which is at odds with the down-regulation of a large portion of cellular transcripts. In this study, we address this paradox by using high-throughput sequencing of cleavage intermediates combined with a custom bioinformatics-based analysis pipeline to identify SOX cleavage sites across the mRNA transcriptome. These data, coupled with targeted mutagenesis, reveal that while cleavage sites are specific and reproducible, they are defined by a degenerate sequence motif containing a small number of conserved residues rather than a strong consensus sequence. This degenerate element is well represented in both human and KSHV mRNA, and its presence correlates with RNA destabilization by SOX. This represents a new endonuclease targeting strategy, in which use of a degenerate targeting element enables RNA cleavage at specific locations without restricting the range of targets. Furthermore, it shows that strong target selectivity can be achieved without a high degree of sequence specificity.",2015 Dec 8,"['Gaglia, Marta Maria', 'Rycroft, Chris H.', 'Glaunsinger, Britt A.']",PLoS Pathog,,,True
fcb1c4ac23381ffb7dbeaad05aa5307cf4386912,PMC,Efficient Structure Resonance Energy Transfer from Microwaves to Confined Acoustic Vibrations in Viruses,http://dx.doi.org/10.1038/srep18030,PMC4673452,26647655,CC BY,"Virus is known to resonate in the confined-acoustic dipolar mode with microwave of the same frequency. However this effect was not considered in previous virus-microwave interaction studies and microwave-based virus epidemic prevention. Here we show that this structure-resonant energy transfer effect from microwaves to virus can be efficient enough so that airborne virus was inactivated with reasonable microwave power density safe for the open public. We demonstrate this effect by measuring the residual viral infectivity of influenza A virus after illuminating microwaves with different frequencies and powers. We also established a theoretical model to estimate the microwaves power threshold for virus inactivation and good agreement with experiments was obtained. Such structure-resonant energy transfer induced inactivation is mainly through physically fracturing the virus structure, which was confirmed by real-time reverse transcription polymerase chain reaction. These results provide a pathway toward establishing a new epidemic prevention strategy in open public for airborne virus.",2015 Dec 9,"['Yang, Szu-Chi', 'Lin, Huan-Chun', 'Liu, Tzu-Ming', 'Lu, Jen-Tang', 'Hung, Wan-Ting', 'Huang, Yu-Ru', 'Tsai, Yi-Chun', 'Kao, Chuan-Liang', 'Chen, Shih-Yuan', 'Sun, Chi-Kuang']",Sci Rep,,,True
6a2f8a34d948eade9535a207c36e6220f2ee1661,PMC,Efficient Structure Resonance Energy Transfer from Microwaves to Confined Acoustic Vibrations in Viruses,http://dx.doi.org/10.1038/srep18030,PMC4673452,26647655,CC BY,"Virus is known to resonate in the confined-acoustic dipolar mode with microwave of the same frequency. However this effect was not considered in previous virus-microwave interaction studies and microwave-based virus epidemic prevention. Here we show that this structure-resonant energy transfer effect from microwaves to virus can be efficient enough so that airborne virus was inactivated with reasonable microwave power density safe for the open public. We demonstrate this effect by measuring the residual viral infectivity of influenza A virus after illuminating microwaves with different frequencies and powers. We also established a theoretical model to estimate the microwaves power threshold for virus inactivation and good agreement with experiments was obtained. Such structure-resonant energy transfer induced inactivation is mainly through physically fracturing the virus structure, which was confirmed by real-time reverse transcription polymerase chain reaction. These results provide a pathway toward establishing a new epidemic prevention strategy in open public for airborne virus.",2015 Dec 9,"['Yang, Szu-Chi', 'Lin, Huan-Chun', 'Liu, Tzu-Ming', 'Lu, Jen-Tang', 'Hung, Wan-Ting', 'Huang, Yu-Ru', 'Tsai, Yi-Chun', 'Kao, Chuan-Liang', 'Chen, Shih-Yuan', 'Sun, Chi-Kuang']",Sci Rep,,,False
0cafb384b401aeefaa3286bb0cf76309434e2288,PMC,Tackling dengue fever: Current status and challenges,http://dx.doi.org/10.1186/s12985-015-0444-8,PMC4673751,26645066,CC BY,"According to recent statistics, 96 million apparent dengue infections were estimated worldwide in 2010. This figure is by far greater than the WHO prediction which indicates the rapid spread of this disease posing a growing threat to the economy and a major challenge to clinicians and health care services across the globe particularly in the affected areas. This article aims at bringing to light the current epidemiological and clinical status of the dengue fever. The relationship between genetic mutations, single nucleotide polymorphism (SNP) and the pathophysiology of disease progression will be put into perspective. It will also highlight the recent advances in dengue vaccine development. Thus far, a significant progress has been made in unraveling the risk factors and understanding the molecular pathogenesis associated with the disease. However, further insights in molecular features of the disease and the development of animal models will enormously help improving the therapeutic interventions and potentially contribute to finding new preventive measures for population at risk.",2015 Dec 9,"['Nedjadi, Taoufik', 'El-Kafrawy, Sherif', 'Sohrab, Sayed S.', 'Desprès, Philippe', 'Damanhouri, Ghazi', 'Azhar, Esam']",Virol J,,,True
3c3068bf6e652c02d85923d2438ad4c84d53071a,PMC,Social Consequences of Ebola Containment Measures in Liberia,http://dx.doi.org/10.1371/journal.pone.0143036,PMC4674104,26650630,CC BY,"INTRODUCTION: In the Ebola Virus Disease (EVD) outbreak in Liberia, two major emergency disease-control measures were cremation of bodies and enforcement of quarantine for asymptomatic individuals suspected of being in contact with a positive case. Enforced by State-related actors, these were promoted as the only method to curtail transmissions as soon as possible. However, as with other harsh measures witnessed by Liberian citizens, in many cases those measures elicited uncontrolled negative reactions within the communities (stigma; fear) that produced, in some cases, the opposite effect of that intended. METHODOLOGY: The research has been conducted in two phases, for a total of 8 weeks. Ethnography of local practices was carried out in 7 neighbourhoods in Monrovia and 5 villages in Grand Cape Mount County in Liberia. 45 Focus Group Discussions (432 participants) and 30 semi-structured interviews sustained the observing participation. Randomly selected people from different social layers were targeted. The principal investigator worked with the help of two local assistants. Perceptions and practices were both analysed. RESULTS: Participants stressed how cremation perpetuated the social breakdown that started with the isolation for the sickness. Socio-economical divides were created by inequitable management of the dead: those who could bribe the burial teams obtained a burial in a private cemetery or the use of Funeral Homes. Conversely, those in economic disadvantage were forced to send their dead for cremation. State-enforced quarantine, with a mandatory prohibition of movement, raised condemnation, strengthened stigmatization and created serious socio-economic distress. Food was distributed intermittently and some houses shared latrines with non-quarantined neighbours. Escapes were also recorded. Study participants narrated how they adopted local measures of containment, through local task forces and socially-rooted control of outsiders. They also stressed how information that was not spread built up rumours and suspicion. CONCLUSIONS: Populations experiencing an epidemic feel a high degree of social insecurity, in addition to the health hazards. Vertical and coercive measures increase mistrust and fear, producing a counter-productive effect in the containment of the epidemic. On the other hand, local communities show a will to be engaged and a high degree of flexibility in participating to the epidemic response. Efforts in the direction of awareness and community involvement could prove to be better strategy to control the epidemic and root the response on social participation.",2015 Dec 9,"['Pellecchia, Umberto', 'Crestani, Rosa', 'Decroo, Tom', 'Van den Bergh, Rafael', 'Al-Kourdi, Yasmine']",PLoS One,,,True
d1963d550043eb5a1d7c49a21530848025ac4eb2,PMC,CD8(+) T-Cells as Immune Regulators of Multiple Sclerosis,http://dx.doi.org/10.3389/fimmu.2015.00619,PMC4674574,26697014,CC BY,"The vast majority of studies regarding the immune basis of MS (and its animal model, EAE) have largely focused on CD4(+) T-cells as mediators and regulators of disease. Interestingly, CD8(+) T-cells represent the predominant T-cell population in human MS lesions and are oligoclonally expanded at the site of pathology. However, their role in the autoimmune pathologic process has been both understudied and controversial. Several animal models and MS patient studies support a pathogenic role for CNS-specific CD8(+) T-cells, whereas we and others have demonstrated a regulatory role for these cells in disease. In this review, we describe studies that have investigated the role of CD8(+) T-cells in MS and EAE, presenting evidence for both pathogenic and regulatory functions. In our studies, we have shown that cytotoxic/suppressor CD8(+) T-cells are CNS antigen-specific, MHC class I-restricted, IFNγ- and perforin-dependent, and are able to inhibit disease. The clinical relevance for CD8(+) T-cell suppressive function is best described by a lack of their function during MS relapse, and importantly, restoration of their suppressive function during quiescence. Furthermore, CD8(+) T-cells with immunosuppressive functions can be therapeutically induced in MS patients by glatiramer acetate (GA) treatment. Unlike CNS-specific CD8(+) T-cells, these immunosuppressive GA-induced CD8(+) T-cells appear to be HLA-E restricted. These studies have provided greater fundamental insight into the role of autoreactive as well as therapeutically induced CD8(+) T-cells in disease amelioration. The clinical implications for these findings are immense and we propose that this natural process can be harnessed toward the development of an effective immunotherapeutic strategy.",2015 Dec 10,"['Sinha, Sushmita', 'Boyden, Alexander W.', 'Itani, Farah R.', 'Crawford, Michael P.', 'Karandikar, Nitin J.']",Front Immunol,,,True
805dabb68b67c8ccf18480c096ffbff3fb90a745,PMC,The baseline characteristics and interim analyses of the high-risk sentinel cohort of the Vietnam Initiative on Zoonotic InfectiONS (VIZIONS),http://dx.doi.org/10.1038/srep17965,PMC4674710,26659094,CC BY,"The Vietnam Initiative for Zoonotic Infections (VIZIONS) includes community-based ‘high-risk sentinel cohort’ (HRSC) studies investigating individuals at risk of zoonotic infection due to occupational or residential exposure to animals. A total of 852 HRSC members were recruited between March 2013 and August 2014 from three provinces (Ha Noi, Dak Lak, and Dong Thap). The most numerous group (72.8%) corresponded to individuals living on farms, followed by slaughterers (16.3%) and animal health workers (8.5%). Nasal/pharyngeal and rectal swabs were collected from HRSC members at recruitment and after notifying illness. Exposure to exotic animals (including wild pigs, porcupine, monkey, civet, bamboo rat and bat) was highest for the Dak Lak cohort (53.7%), followed by Ha Noi (13.7%) and Dong Thap (4.0%). A total of 26.8% of individuals reported consumption of raw blood over the previous year; 33.6% slaughterers reported no use of protective equipment at work. Over 686 person-years of observation, 213 episodes of suspect infectious disease were notified, equivalent of 0.35 reports per person-year. Responsive samples were collected from animals in the farm cohort. There was noticeable time and space clustering of disease episodes suggesting that the VIZIONS set up is also suitable for the formal epidemiological investigation of disease outbreaks.",2015 Dec 10,"['Carrique-Mas, Juan J.', 'Tue, Ngo T.', 'Bryant, Juliet E.', 'Saylors, Karen', 'Cuong, Nguyen V.', 'Hoa, Ngo T.', 'An, Nguyen N.', 'Hien, Vo B.', 'Lao, Pham V.', 'Tu, Nguyen C.', 'Chuyen, Nguyen K.', 'Chuc, Nguyen T.K.', 'Tan, Dinh V.', 'Duong, Hoang Van V.', 'Toan, Tran K.', 'Chi, Nguyen T.Y.', 'Campbell, James', 'Rabaa, Maia A.', 'Nadjm, Behzad', 'Woolhouse, Mark', 'Wertheim, Heiman', 'Thwaites, Guy', 'Baker, Stephen']",Sci Rep,,,True
2e0fdaf23e6de0d6787519f671bc198d47f3acb1,PMC,ORBiT: Oak Ridge biosurveillance toolkit for public health dynamics,http://dx.doi.org/10.1186/1471-2105-16-S17-S4,PMC4674898,26679008,CC BY,"BACKGROUND: The digitization of health-related information through electronic health records (EHR) and electronic healthcare reimbursement claims and the continued growth of self-reported health information through social media provides both tremendous opportunities and challenges in developing effective biosurveillance tools. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build systems that can track, monitor and report such events in a timely manner. Further, it is also important to identify susceptible geographic regions and populations where emerging diseases may have a significant impact. METHODS: In this paper, we present an overview of Oak Ridge Biosurveillance Toolkit (ORBiT), which we have developed specifically to address data analytic challenges in the realm of public health surveillance. In particular, ORBiT provides an extensible environment to pull together diverse, large-scale datasets and analyze them to identify spatial and temporal patterns for various biosurveillance-related tasks. RESULTS: We demonstrate the utility of ORBiT in automatically extracting a small number of spatial and temporal patterns during the 2009-2010 pandemic H1N1 flu season using claims data. These patterns provide quantitative insights into the dynamics of how the pandemic flu spread across different parts of the country. We discovered that the claims data exhibits multi-scale patterns from which we could identify a small number of states in the United States (US) that act as ""bridge regions"" contributing to one or more specific influenza spread patterns. Similar to previous studies, the patterns show that the south-eastern regions of the US were widely affected by the H1N1 flu pandemic. Several of these south-eastern states act as bridge regions, which connect the north-east and central US in terms of flu occurrences. CONCLUSIONS: These quantitative insights show how the claims data combined with novel analytical techniques can provide important information to decision makers when an epidemic spreads throughout the country. Taken together ORBiT provides a scalable and extensible platform for public health surveillance.",2015 Dec 7,"['Ramanathan, Arvind', 'Pullum, Laura L', 'Hobson, Tanner C', 'Steed, Chad A', 'Quinn, Shannon P', 'Chennubhotla, Chakra S', 'Valkova, Silvia']",BMC Bioinformatics,,,True
6fe8d33a03f951e2b85def26fa987ea1e98d5c0e,PMC,Assessing Ebola-related web search behaviour: insights and implications from an analytical study of Google Trends-based query volumes,http://dx.doi.org/10.1186/s40249-015-0090-9,PMC4674955,26654247,CC BY,"BACKGROUND: The 2014 Ebola epidemic in West Africa has attracted public interest worldwide, leading to millions of Ebola-related Internet searches being performed during the period of the epidemic. This study aimed to evaluate and interpret Google search queries for terms related to the Ebola outbreak both at the global level and in all countries where primary cases of Ebola occurred. The study also endeavoured to look at the correlation between the number of overall and weekly web searches and the number of overall and weekly new cases of Ebola. METHODS: Google Trends (GT) was used to explore Internet activity related to Ebola. The study period was from 29 December 2013 to 14 June 2015. Pearson’s correlation was performed to correlate Ebola-related relative search volumes (RSVs) with the number of weekly and overall Ebola cases. Multivariate regression was performed using Ebola-related RSV as a dependent variable, and the overall number of Ebola cases and the Human Development Index were used as predictor variables. RESULTS: The greatest RSV was registered in the three West African countries mainly affected by the Ebola epidemic. The queries varied in the different countries. Both quantitative and qualitative differences between the affected African countries and other Western countries with primary cases were noted, in relation to the different flux volumes and different time courses. In the affected African countries, web query search volumes were mostly concentrated in the capital areas. However, in Western countries, web queries were uniformly distributed over the national territory. In terms of the three countries mainly affected by the Ebola epidemic, the correlation between the number of new weekly cases of Ebola and the weekly GT index varied from weak to moderate. The correlation between the number of Ebola cases registered in all countries during the study period and the GT index was very high. CONCLUSION: Google Trends showed a coarse-grained nature, strongly correlating with global epidemiological data, but was weaker at country level, as it was prone to distortions induced by unbalanced media coverage and the digital divide. Global and local health agencies could usefully exploit GT data to identify disease-related information needs and plan proper communication strategies, particularly in the case of health-threatening events. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-015-0090-9) contains supplementary material, which is available to authorized users.",2015 Dec 10,"['Alicino, Cristiano', 'Bragazzi, Nicola Luigi', 'Faccio, Valeria', 'Amicizia, Daniela', 'Panatto, Donatella', 'Gasparini, Roberto', 'Icardi, Giancarlo', 'Orsi, Andrea']",Infect Dis Poverty,,,False
47c38815f36cc14e7160f1890cda9f39b7e1d778,PMC,Assessing Ebola-related web search behaviour: insights and implications from an analytical study of Google Trends-based query volumes,http://dx.doi.org/10.1186/s40249-015-0090-9,PMC4674955,26654247,CC BY,"BACKGROUND: The 2014 Ebola epidemic in West Africa has attracted public interest worldwide, leading to millions of Ebola-related Internet searches being performed during the period of the epidemic. This study aimed to evaluate and interpret Google search queries for terms related to the Ebola outbreak both at the global level and in all countries where primary cases of Ebola occurred. The study also endeavoured to look at the correlation between the number of overall and weekly web searches and the number of overall and weekly new cases of Ebola. METHODS: Google Trends (GT) was used to explore Internet activity related to Ebola. The study period was from 29 December 2013 to 14 June 2015. Pearson’s correlation was performed to correlate Ebola-related relative search volumes (RSVs) with the number of weekly and overall Ebola cases. Multivariate regression was performed using Ebola-related RSV as a dependent variable, and the overall number of Ebola cases and the Human Development Index were used as predictor variables. RESULTS: The greatest RSV was registered in the three West African countries mainly affected by the Ebola epidemic. The queries varied in the different countries. Both quantitative and qualitative differences between the affected African countries and other Western countries with primary cases were noted, in relation to the different flux volumes and different time courses. In the affected African countries, web query search volumes were mostly concentrated in the capital areas. However, in Western countries, web queries were uniformly distributed over the national territory. In terms of the three countries mainly affected by the Ebola epidemic, the correlation between the number of new weekly cases of Ebola and the weekly GT index varied from weak to moderate. The correlation between the number of Ebola cases registered in all countries during the study period and the GT index was very high. CONCLUSION: Google Trends showed a coarse-grained nature, strongly correlating with global epidemiological data, but was weaker at country level, as it was prone to distortions induced by unbalanced media coverage and the digital divide. Global and local health agencies could usefully exploit GT data to identify disease-related information needs and plan proper communication strategies, particularly in the case of health-threatening events. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-015-0090-9) contains supplementary material, which is available to authorized users.",2015 Dec 10,"['Alicino, Cristiano', 'Bragazzi, Nicola Luigi', 'Faccio, Valeria', 'Amicizia, Daniela', 'Panatto, Donatella', 'Gasparini, Roberto', 'Icardi, Giancarlo', 'Orsi, Andrea']",Infect Dis Poverty,,,True
803e5ac0891c5ae6a165ca754e04fcfbb6e06394,PMC,Identification of climate factors related to human infection with avian influenza A H7N9 and H5N1 viruses in China,http://dx.doi.org/10.1038/srep18094,PMC4676028,26656876,CC BY,"Human influenza infections display a strongly seasonal pattern. However, whether H7N9 and H5N1 infections correlate with climate factors has not been examined. Here, we analyzed 350 cases of H7N9 infection and 47 cases of H5N1 infection. The spatial characteristics of these cases revealed that H5N1 infections mainly occurred in the South, Middle, and Northwest of China, while the occurrence of H7N9 was concentrated in coastal areas of East and South of China. Aside from spatial-temporal characteristics, the most adaptive meteorological conditions for the occurrence of human infections by these two viral subtypes were different. We found that H7N9 infections correlate with climate factors, especially temperature (TEM) and relative humidity (RHU), while H5N1 infections correlate with TEM and atmospheric pressure (PRS). Hence, we propose a risky window (TEM 4–14 °C and RHU 65–95%) for H7N9 infection and (TEM 2–22 °C and PRS 980-1025 kPa) for H5N1 infection. Our results represent the first step in determining the effects of climate factors on two different virus infections in China and provide warning guidelines for the future when provinces fall into the risky windows. These findings revealed integrated predictive meteorological factors rooted in statistic data that enable the establishment of preventive actions and precautionary measures against future outbreaks.",2015 Dec 11,"['Li, Jing', 'Rao, Yuhan', 'Sun, Qinglan', 'Wu, Xiaoxu', 'Jin, Jiao', 'Bi, Yuhai', 'Chen, Jin', 'Lei, Fumin', 'Liu, Qiyong', 'Duan, Ziyuan', 'Ma, Juncai', 'Gao, George F.', 'Liu, Di', 'Liu, Wenjun']",Sci Rep,,,True
3e77f816d34625139df9452b46df14df6726b390,PMC,Identification of climate factors related to human infection with avian influenza A H7N9 and H5N1 viruses in China,http://dx.doi.org/10.1038/srep18094,PMC4676028,26656876,CC BY,"Human influenza infections display a strongly seasonal pattern. However, whether H7N9 and H5N1 infections correlate with climate factors has not been examined. Here, we analyzed 350 cases of H7N9 infection and 47 cases of H5N1 infection. The spatial characteristics of these cases revealed that H5N1 infections mainly occurred in the South, Middle, and Northwest of China, while the occurrence of H7N9 was concentrated in coastal areas of East and South of China. Aside from spatial-temporal characteristics, the most adaptive meteorological conditions for the occurrence of human infections by these two viral subtypes were different. We found that H7N9 infections correlate with climate factors, especially temperature (TEM) and relative humidity (RHU), while H5N1 infections correlate with TEM and atmospheric pressure (PRS). Hence, we propose a risky window (TEM 4–14 °C and RHU 65–95%) for H7N9 infection and (TEM 2–22 °C and PRS 980-1025 kPa) for H5N1 infection. Our results represent the first step in determining the effects of climate factors on two different virus infections in China and provide warning guidelines for the future when provinces fall into the risky windows. These findings revealed integrated predictive meteorological factors rooted in statistic data that enable the establishment of preventive actions and precautionary measures against future outbreaks.",2015 Dec 11,"['Li, Jing', 'Rao, Yuhan', 'Sun, Qinglan', 'Wu, Xiaoxu', 'Jin, Jiao', 'Bi, Yuhai', 'Chen, Jin', 'Lei, Fumin', 'Liu, Qiyong', 'Duan, Ziyuan', 'Ma, Juncai', 'Gao, George F.', 'Liu, Di', 'Liu, Wenjun']",Sci Rep,,,False
dbd589ba5a6b57f60ccafcf475c57a88211ff95e,PMC,"Genomic legacy of the African cheetah, Acinonyx jubatus",http://dx.doi.org/10.1186/s13059-015-0837-4,PMC4676127,26653294,CC BY,"BACKGROUND: Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations. RESULTS: Here the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one >100,000 years ago coincident with cheetah migrations out of the Americas and into Eurasia and Africa, and a second 11,084–12,589 years ago in Africa coincident with late Pleistocene large mammal extinctions. MHC class I gene loss and dramatic reduction in functional diversity of MHC genes would explain why cheetahs ablate skin graft rejection among unrelated individuals. Significant excess of non-synonymous mutations in AKAP4 (p<0.02), a gene mediating spermatozoon development, indicates cheetah fixation of five function-damaging amino acid variants distinct from AKAP4 homologues of other Felidae or mammals; AKAP4 dysfunction may cause the cheetah’s extremely high (>80 %) pleiomorphic sperm. CONCLUSIONS: The study provides an unprecedented genomic perspective for the rare cheetah, with potential relevance to the species’ natural history, physiological adaptations and unique reproductive disposition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0837-4) contains supplementary material, which is available to authorized users.",2015 Dec 10,"['Dobrynin, Pavel', 'Liu, Shiping', 'Tamazian, Gaik', 'Xiong, Zijun', 'Yurchenko, Andrey A.', 'Krasheninnikova, Ksenia', 'Kliver, Sergey', 'Schmidt-Küntzel, Anne', 'Koepfli, Klaus-Peter', 'Johnson, Warren', 'Kuderna, Lukas F.K.', 'García-Pérez, Raquel', 'Manuel, Marc de', 'Godinez, Ricardo', 'Komissarov, Aleksey', 'Makunin, Alexey', 'Brukhin, Vladimir', 'Qiu, Weilin', 'Zhou, Long', 'Li, Fang', 'Yi, Jian', 'Driscoll, Carlos', 'Antunes, Agostinho', 'Oleksyk, Taras K.', 'Eizirik, Eduardo', 'Perelman, Polina', 'Roelke, Melody', 'Wildt, David', 'Diekhans, Mark', 'Marques-Bonet, Tomas', 'Marker, Laurie', 'Bhak, Jong', 'Wang, Jun', 'Zhang, Guojie', 'O’Brien, Stephen J.']",Genome Biol,,,True
20c2e99b2e557513c61d82a9d291b809eafaf70e,PMC,"Genomic legacy of the African cheetah, Acinonyx jubatus",http://dx.doi.org/10.1186/s13059-015-0837-4,PMC4676127,26653294,CC BY,"BACKGROUND: Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations. RESULTS: Here the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one >100,000 years ago coincident with cheetah migrations out of the Americas and into Eurasia and Africa, and a second 11,084–12,589 years ago in Africa coincident with late Pleistocene large mammal extinctions. MHC class I gene loss and dramatic reduction in functional diversity of MHC genes would explain why cheetahs ablate skin graft rejection among unrelated individuals. Significant excess of non-synonymous mutations in AKAP4 (p<0.02), a gene mediating spermatozoon development, indicates cheetah fixation of five function-damaging amino acid variants distinct from AKAP4 homologues of other Felidae or mammals; AKAP4 dysfunction may cause the cheetah’s extremely high (>80 %) pleiomorphic sperm. CONCLUSIONS: The study provides an unprecedented genomic perspective for the rare cheetah, with potential relevance to the species’ natural history, physiological adaptations and unique reproductive disposition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0837-4) contains supplementary material, which is available to authorized users.",2015 Dec 10,"['Dobrynin, Pavel', 'Liu, Shiping', 'Tamazian, Gaik', 'Xiong, Zijun', 'Yurchenko, Andrey A.', 'Krasheninnikova, Ksenia', 'Kliver, Sergey', 'Schmidt-Küntzel, Anne', 'Koepfli, Klaus-Peter', 'Johnson, Warren', 'Kuderna, Lukas F.K.', 'García-Pérez, Raquel', 'Manuel, Marc de', 'Godinez, Ricardo', 'Komissarov, Aleksey', 'Makunin, Alexey', 'Brukhin, Vladimir', 'Qiu, Weilin', 'Zhou, Long', 'Li, Fang', 'Yi, Jian', 'Driscoll, Carlos', 'Antunes, Agostinho', 'Oleksyk, Taras K.', 'Eizirik, Eduardo', 'Perelman, Polina', 'Roelke, Melody', 'Wildt, David', 'Diekhans, Mark', 'Marques-Bonet, Tomas', 'Marker, Laurie', 'Bhak, Jong', 'Wang, Jun', 'Zhang, Guojie', 'O’Brien, Stephen J.']",Genome Biol,,,True
df794557c0c0da0a84d28c5df7f3748560fde11f,PMC,"Genomic legacy of the African cheetah, Acinonyx jubatus",http://dx.doi.org/10.1186/s13059-015-0837-4,PMC4676127,26653294,CC BY,"BACKGROUND: Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations. RESULTS: Here the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one >100,000 years ago coincident with cheetah migrations out of the Americas and into Eurasia and Africa, and a second 11,084–12,589 years ago in Africa coincident with late Pleistocene large mammal extinctions. MHC class I gene loss and dramatic reduction in functional diversity of MHC genes would explain why cheetahs ablate skin graft rejection among unrelated individuals. Significant excess of non-synonymous mutations in AKAP4 (p<0.02), a gene mediating spermatozoon development, indicates cheetah fixation of five function-damaging amino acid variants distinct from AKAP4 homologues of other Felidae or mammals; AKAP4 dysfunction may cause the cheetah’s extremely high (>80 %) pleiomorphic sperm. CONCLUSIONS: The study provides an unprecedented genomic perspective for the rare cheetah, with potential relevance to the species’ natural history, physiological adaptations and unique reproductive disposition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0837-4) contains supplementary material, which is available to authorized users.",2015 Dec 10,"['Dobrynin, Pavel', 'Liu, Shiping', 'Tamazian, Gaik', 'Xiong, Zijun', 'Yurchenko, Andrey A.', 'Krasheninnikova, Ksenia', 'Kliver, Sergey', 'Schmidt-Küntzel, Anne', 'Koepfli, Klaus-Peter', 'Johnson, Warren', 'Kuderna, Lukas F.K.', 'García-Pérez, Raquel', 'Manuel, Marc de', 'Godinez, Ricardo', 'Komissarov, Aleksey', 'Makunin, Alexey', 'Brukhin, Vladimir', 'Qiu, Weilin', 'Zhou, Long', 'Li, Fang', 'Yi, Jian', 'Driscoll, Carlos', 'Antunes, Agostinho', 'Oleksyk, Taras K.', 'Eizirik, Eduardo', 'Perelman, Polina', 'Roelke, Melody', 'Wildt, David', 'Diekhans, Mark', 'Marques-Bonet, Tomas', 'Marker, Laurie', 'Bhak, Jong', 'Wang, Jun', 'Zhang, Guojie', 'O’Brien, Stephen J.']",Genome Biol,,,True
9538da236dd88828d491e85addc5b2c6669e7c5a,PMC,Burden of respiratory syncytial virus infections in China: Systematic review and meta–analysis,http://dx.doi.org/10.7189/jogh.05.020417,PMC4676581,26682049,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is the most important cause of acute respiratory tract infection (ARTI) related morbidity and mortality worldwide. However, the disease burden due to RSV has not been systematically summarized in China. METHOD: A systematic search was performed in the Chinese BioMedical Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and PubMed to identify available published RSV studies in China. RESULTS: A total of 489 641 patients with ARTIs from 135 studies were included in the analysis. Among patients with ARTIs, RSV accounted for 18.7% (95% confidence interval CI 17.1–20.5%). The prevalence of RSV was highest in infants (26.5%, 95% CI 23.7–29.5%) and lowest in those aged ≥16 years (2.8%, 95% CI 1.3–6.1). A higher prevalence of RSV was seen in inpatients (22%, 95% CI 19.9–24.2%) than in outpatients (14%, 95% CI 9.6–19.9%). RSV type A accounted for 63.1% (95% CI 52.3–72.8%) of all RSV infections. RSV infections occurred mainly in winter and spring. The most common clinical manifestations were cough, production of sputum, wheezing and fever. CONCLUSION: RSV is the leading cause of viral ARTIs in China, particularly in infants and young children. Our findings are valuable for guiding the selection of appropriate therapies for ARTIs and implementation of preventive measures against RSV infections. Our data further supports the development of a successful RSV vaccine as a high priority.",,"['Zhang, Yaowen', 'Yuan, Lichao', 'Zhang, Yongming', 'Zhang, Xiuping', 'Zheng, Minghuan', 'Kyaw, Moe H']",J Glob Health.; 5(2):020417,,,True
0851abc9f5ae5d1c1225f665b8ddd13a7c905179,PMC,Burden of respiratory syncytial virus infections in China: Systematic review and meta–analysis,http://dx.doi.org/10.7189/jogh.05.020417,PMC4676581,26682049,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is the most important cause of acute respiratory tract infection (ARTI) related morbidity and mortality worldwide. However, the disease burden due to RSV has not been systematically summarized in China. METHOD: A systematic search was performed in the Chinese BioMedical Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and PubMed to identify available published RSV studies in China. RESULTS: A total of 489 641 patients with ARTIs from 135 studies were included in the analysis. Among patients with ARTIs, RSV accounted for 18.7% (95% confidence interval CI 17.1–20.5%). The prevalence of RSV was highest in infants (26.5%, 95% CI 23.7–29.5%) and lowest in those aged ≥16 years (2.8%, 95% CI 1.3–6.1). A higher prevalence of RSV was seen in inpatients (22%, 95% CI 19.9–24.2%) than in outpatients (14%, 95% CI 9.6–19.9%). RSV type A accounted for 63.1% (95% CI 52.3–72.8%) of all RSV infections. RSV infections occurred mainly in winter and spring. The most common clinical manifestations were cough, production of sputum, wheezing and fever. CONCLUSION: RSV is the leading cause of viral ARTIs in China, particularly in infants and young children. Our findings are valuable for guiding the selection of appropriate therapies for ARTIs and implementation of preventive measures against RSV infections. Our data further supports the development of a successful RSV vaccine as a high priority.",,"['Zhang, Yaowen', 'Yuan, Lichao', 'Zhang, Yongming', 'Zhang, Xiuping', 'Zheng, Minghuan', 'Kyaw, Moe H']",J Glob Health.; 5(2):020417,,,False
e88797458f110553b9418007d35401975dce1454,PMC,Respiratory Syncytial Virus Uses CX3CR1 as a Receptor on Primary Human Airway Epithelial Cultures,http://dx.doi.org/10.1371/journal.ppat.1005318,PMC4676609,26658574,CC BY,"Respiratory syncytial virus (RSV) is the most frequent cause of lower respiratory disease in infants, but no vaccine or effective therapy is available. The initiation of RSV infection of immortalized cells is largely dependent on cell surface heparan sulfate (HS), a receptor for the RSV attachment (G) glycoprotein in immortalized cells. However, RSV infects the ciliated cells in primary well differentiated human airway epithelial (HAE) cultures via the apical surface, but HS is not detectable on this surface. Here we show that soluble HS inhibits infection of immortalized cells, but not HAE cultures, confirming that HS is not the receptor on HAE cultures. Conversely, a “non-neutralizing” monoclonal antibody against the G protein that does not block RSV infection of immortalized cells, does inhibit infection of HAE cultures. This antibody was previously shown to block the interaction between the G protein and the chemokine receptor CX3CR1 and we have mapped the binding site for this antibody to the CX3C motif and its surrounding region in the G protein. We show that CX3CR1 is present on the apical surface of ciliated cells in HAE cultures and especially on the cilia. RSV infection of HAE cultures is reduced by an antibody against CX3CR1 and by mutations in the G protein CX3C motif. Additionally, mice lacking CX3CR1 are less susceptible to RSV infection. These findings demonstrate that RSV uses CX3CR1 as a cellular receptor on HAE cultures and highlight the importance of using a physiologically relevant model to study virus entry and antibody neutralization.",2015 Dec 11,"['Johnson, Sara M.', 'McNally, Beth A.', 'Ioannidis, Ioannis', 'Flano, Emilio', 'Teng, Michael N.', 'Oomens, Antonius G.', 'Walsh, Edward E.', 'Peeples, Mark E.']",PLoS Pathog,,,True
b4e98770894089e276f91c1d00e58c8885708e11,PMC,Evaluation of a combined MxA and CRP point-of-care immunoassay to identify viral and/or bacterial immune response in patients with acute febrile respiratory infection,http://dx.doi.org/10.3402/ecrj.v2.28245,PMC4676840,26672961,CC BY,"BACKGROUND: Challenges in the clinical differentiation of viral and/or bacterial respiratory infection lead to the misappropriation of antibiotics and increased healthcare costs. A tool to facilitate rapid and accurate point-of-care (POC) differentiation is needed. METHODS AND FINDINGS: A prospective, single center, blinded, observational clinical trial was conducted at Beth Israel Deaconess Medical Center from December 2012 to August 2013 to determine the accuracy of a POC immunoassay to identify a clinically significant immune response to viral and/or bacterial infection. Sixty patients with acute febrile respiratory infection (19 pharyngitis and 41 lower respiratory tract infection [LRTI]) were enrolled. Participants provided fingerstick blood for immunoassay testing (myxovirus A [MxA] and c-reactive protein [CRP]) and four oropharyngeal samples for viral PCR and routine bacterial cell culture. A venous blood sample was collected. An ELISA was used to measure CRP and MxA. Paired serological testing was used to confirm atypical bacteria. A urine sample was provided for Streptococcus and Legionella antigen testing. Patients with suspected LRTI had sputum and blood cultures, chest X-ray, and WBC count measured. Viral infection was confirmed if oropharyngeal PCR was positive for viral pathogens. Bacterial infection was confirmed in positive throat or sputum cultures. Elevated immunoglobulin M antibodies or twofold increase in IgG antibodies between acute and convalescent phase indicated atypical bacteria. Positive Streptococcus or Legionella urine antigen assays also confirmed bacterial infection. The immunoassay correctly categorized subjects as 92% (22/24) negative, 80% (16/20) with bacterial infection, and 70% (7/10) with viral infection. CONCLUSIONS: The interplay between an MxA value and a semi-quantitative CRP value can aid in the differentiation of infectious etiology. In isolation, neither MxA nor CRP alone is sensitive or specific. However, the pattern of results in a rapid immunoassay provides a sensitive and specific method to differentiate acute febrile respiratory infections. This diagnostic information may help reduce antibiotic misuse and resistance and lower healthcare costs.",2015 Dec 10,"['Sambursky, Robert', 'Shapiro, Nathan']",Eur Clin Respir J,,,True
7cb443aaa8612c98630f7ecc02ec070a547f4d9f,PMC,Evaluation of a combined MxA and CRP point-of-care immunoassay to identify viral and/or bacterial immune response in patients with acute febrile respiratory infection,http://dx.doi.org/10.3402/ecrj.v2.28245,PMC4676840,26672961,CC BY,"BACKGROUND: Challenges in the clinical differentiation of viral and/or bacterial respiratory infection lead to the misappropriation of antibiotics and increased healthcare costs. A tool to facilitate rapid and accurate point-of-care (POC) differentiation is needed. METHODS AND FINDINGS: A prospective, single center, blinded, observational clinical trial was conducted at Beth Israel Deaconess Medical Center from December 2012 to August 2013 to determine the accuracy of a POC immunoassay to identify a clinically significant immune response to viral and/or bacterial infection. Sixty patients with acute febrile respiratory infection (19 pharyngitis and 41 lower respiratory tract infection [LRTI]) were enrolled. Participants provided fingerstick blood for immunoassay testing (myxovirus A [MxA] and c-reactive protein [CRP]) and four oropharyngeal samples for viral PCR and routine bacterial cell culture. A venous blood sample was collected. An ELISA was used to measure CRP and MxA. Paired serological testing was used to confirm atypical bacteria. A urine sample was provided for Streptococcus and Legionella antigen testing. Patients with suspected LRTI had sputum and blood cultures, chest X-ray, and WBC count measured. Viral infection was confirmed if oropharyngeal PCR was positive for viral pathogens. Bacterial infection was confirmed in positive throat or sputum cultures. Elevated immunoglobulin M antibodies or twofold increase in IgG antibodies between acute and convalescent phase indicated atypical bacteria. Positive Streptococcus or Legionella urine antigen assays also confirmed bacterial infection. The immunoassay correctly categorized subjects as 92% (22/24) negative, 80% (16/20) with bacterial infection, and 70% (7/10) with viral infection. CONCLUSIONS: The interplay between an MxA value and a semi-quantitative CRP value can aid in the differentiation of infectious etiology. In isolation, neither MxA nor CRP alone is sensitive or specific. However, the pattern of results in a rapid immunoassay provides a sensitive and specific method to differentiate acute febrile respiratory infections. This diagnostic information may help reduce antibiotic misuse and resistance and lower healthcare costs.",2015 Dec 10,"['Sambursky, Robert', 'Shapiro, Nathan']",Eur Clin Respir J,,,False
8bf449477aff84ef0591f10731a654610a5126b7,PMC,Gene silencing of TACE enhances plaque stability and improves vascular remodeling in a rabbit model of atherosclerosis,http://dx.doi.org/10.1038/srep17939,PMC4677302,26655882,CC BY,"We aimed to test the hypothesis that gene silencing of tumor necrosis factor alpha converting enzyme (TACE) may attenuate lesion inflammation and positive vascular remodeling and enhance plaque stability in a rabbit model of atherosclerosis. Lentivirus-mediated TACE shRNA was injected into the abdominal aortic plaques of rabbits which effectively down-regulated TACE expression and activities from week 8 to week 16. TACE gene silencing reduced remodeling index and plaque burden, and diminished the content of macrophages and lipids while increased that of smooth muscle cells and collagen in the aortic plaques. In addition, TACE gene silencing attenuated the local expression of P65, iNOS, ICAM-1, VEGF and Flt-1 and activities of MMP9 and MMP2 while increased the local expression of TGF-β1 together with reduced number of neovessels in the aorta. TACE shRNA treatment resulted in down-regulated expression of TACE in macrophages and blunted ERK-P38 phosphorylation and tube formation of co-cultured mouse vascular smooth muscle cells or human umbilical vein endothelial cells. In conclusion, gene silencing of TACE enhanced plaque stability and improved vascular positive remodeling. The mechanisms may involve attenuated local inflammation, neovascularization and MMP activation, as well as enhanced collagen production probably via down-regulated ERK-NF-κB and up-regulated TGF-β1 signaling pathways.",2015 Dec 14,"['Zhao, Xueqiang', 'Kong, Jing', 'Zhao, Yuxia', 'Wang, Xuping', 'Bu, Peili', 'Zhang, Cheng', 'Zhang, Yun']",Sci Rep,,,True
1412106d8254d159356dda94db652655e51bd729,PMC,CVTree3 Web Server for Whole-genome-based and Alignment-free Prokaryotic Phylogeny and Taxonomy,http://dx.doi.org/10.1016/j.gpb.2015.08.004,PMC4678791,26563468,CC BY,"A faithful phylogeny and an objective taxonomy for prokaryotes should agree with each other and ultimately follow the genome data. With the number of sequenced genomes reaching tens of thousands, both tree inference and detailed comparison with taxonomy are great challenges. We now provide one solution in the latest Release 3.0 of the alignment-free and whole-genome-based web server CVTree3. The server resides in a cluster of 64 cores and is equipped with an interactive, collapsible, and expandable tree display. It is capable of comparing the tree branching order with prokaryotic classification at all taxonomic ranks from domains down to species and strains. CVTree3 allows for inquiry by taxon names and trial on lineage modifications. In addition, it reports a summary of monophyletic and non-monophyletic taxa at all ranks as well as produces print-quality subtree figures. After giving an overview of retrospective verification of the CVTree approach, the power of the new server is described for the mega-classification of prokaryotes and determination of taxonomic placement of some newly-sequenced genomes. A few discrepancies between CVTree and 16S rRNA analyses are also summarized with regard to possible taxonomic revisions. CVTree3 is freely accessible to all users at http://tlife.fudan.edu.cn/cvtree3/ without login requirements.",2015 Oct 10,"['Zuo, Guanghong', 'Hao, Bailin']",Genomics Proteomics Bioinformatics,,,False
8f9fb1b2ed8b56d2524c9cf458277e377711397c,PMC,CVTree3 Web Server for Whole-genome-based and Alignment-free Prokaryotic Phylogeny and Taxonomy,http://dx.doi.org/10.1016/j.gpb.2015.08.004,PMC4678791,26563468,CC BY,"A faithful phylogeny and an objective taxonomy for prokaryotes should agree with each other and ultimately follow the genome data. With the number of sequenced genomes reaching tens of thousands, both tree inference and detailed comparison with taxonomy are great challenges. We now provide one solution in the latest Release 3.0 of the alignment-free and whole-genome-based web server CVTree3. The server resides in a cluster of 64 cores and is equipped with an interactive, collapsible, and expandable tree display. It is capable of comparing the tree branching order with prokaryotic classification at all taxonomic ranks from domains down to species and strains. CVTree3 allows for inquiry by taxon names and trial on lineage modifications. In addition, it reports a summary of monophyletic and non-monophyletic taxa at all ranks as well as produces print-quality subtree figures. After giving an overview of retrospective verification of the CVTree approach, the power of the new server is described for the mega-classification of prokaryotes and determination of taxonomic placement of some newly-sequenced genomes. A few discrepancies between CVTree and 16S rRNA analyses are also summarized with regard to possible taxonomic revisions. CVTree3 is freely accessible to all users at http://tlife.fudan.edu.cn/cvtree3/ without login requirements.",2015 Oct 10,"['Zuo, Guanghong', 'Hao, Bailin']",Genomics Proteomics Bioinformatics,,,False
5706247afd9585354f3dae2f70d200a25f8e3f4c,PMC,"Discovery of novel virus sequences in an isolated and threatened bat species, the New Zealand lesser short-tailed bat (Mystacina tuberculata)",http://dx.doi.org/10.1099/vir.0.000158,PMC4681071,25900137,CC BY,"Bats harbour a diverse array of viruses, including significant human pathogens. Extensive metagenomic studies of material from bats, in particular guano, have revealed a large number of novel or divergent viral taxa that were previously unknown. New Zealand has only two extant indigenous terrestrial mammals, which are both bats, Mystacina tuberculata (the lesser short-tailed bat) and Chalinolobus tuberculatus (the long-tailed bat). Until the human introduction of exotic mammals, these species had been isolated from all other terrestrial mammals for over 1 million years (potentially over 16 million years for M. tuberculata). Four bat guano samples were collected from M. tuberculata roosts on the isolated offshore island of Whenua hou (Codfish Island) in New Zealand. Metagenomic analysis revealed that this species still hosts a plethora of divergent viruses. Whilst the majority of viruses detected were likely to be of dietary origin, some putative vertebrate virus sequences were identified. Papillomavirus, polyomavirus, calicivirus and hepevirus were found in the metagenomic data and subsequently confirmed using independent PCR assays and sequencing. The new hepevirus and calicivirus sequences may represent new genera within these viral families. Our findings may provide an insight into the origins of viral families, given their detection in an isolated host species.",2015 Aug,"['Wang, Jing', 'Moore, Nicole E.', 'Murray, Zak L.', 'McInnes, Kate', 'White, Daniel J.', 'Tompkins, Daniel M.', 'Hall, Richard J.']",J Gen Virol,,,True
2ed563bcb94b0dd5bb3081be75d5173c447e7314,PMC,"Discovery of novel virus sequences in an isolated and threatened bat species, the New Zealand lesser short-tailed bat (Mystacina tuberculata)",http://dx.doi.org/10.1099/vir.0.000158,PMC4681071,25900137,CC BY,"Bats harbour a diverse array of viruses, including significant human pathogens. Extensive metagenomic studies of material from bats, in particular guano, have revealed a large number of novel or divergent viral taxa that were previously unknown. New Zealand has only two extant indigenous terrestrial mammals, which are both bats, Mystacina tuberculata (the lesser short-tailed bat) and Chalinolobus tuberculatus (the long-tailed bat). Until the human introduction of exotic mammals, these species had been isolated from all other terrestrial mammals for over 1 million years (potentially over 16 million years for M. tuberculata). Four bat guano samples were collected from M. tuberculata roosts on the isolated offshore island of Whenua hou (Codfish Island) in New Zealand. Metagenomic analysis revealed that this species still hosts a plethora of divergent viruses. Whilst the majority of viruses detected were likely to be of dietary origin, some putative vertebrate virus sequences were identified. Papillomavirus, polyomavirus, calicivirus and hepevirus were found in the metagenomic data and subsequently confirmed using independent PCR assays and sequencing. The new hepevirus and calicivirus sequences may represent new genera within these viral families. Our findings may provide an insight into the origins of viral families, given their detection in an isolated host species.",2015 Aug,"['Wang, Jing', 'Moore, Nicole E.', 'Murray, Zak L.', 'McInnes, Kate', 'White, Daniel J.', 'Tompkins, Daniel M.', 'Hall, Richard J.']",J Gen Virol,,,False
51f8792fd26cd2c094c1b2d0e5539902fb6221da,PMC,People at Risk of Influenza Pandemics: The Evolution of Perception and Behavior,http://dx.doi.org/10.1371/journal.pone.0144868,PMC4682843,26658371,CC BY,"Influenza pandemics can severely impact human health and society. Understanding public perception and behavior toward influenza pandemics is important for minimizing the effects of such events. Public perception and behavior are expected to change over the course of an influenza pandemic, but this idea has received little attention in previous studies. Our study aimed to understand the dynamics of public perception and behavior over the course of the 2009 H1N1 influenza pandemic. Three consecutive cross-sectional surveys were administered among Beijing residents with random-digit dialing techniques in March 2008 and August and November 2009. Effective samples of 507, 508 and 1006 respondents were interviewed in each of the three surveys, respectively. The mean scores of risk perception were low to moderate across the three surveys. The perceived risk of infection of self was significantly lower than that of the community, revealing an optimistic bias. Longitudinally, the perceived risk of contracting H1N1 increased, whereas the perceived risk of being unable to obtain medicine and medical care once influenza permeated the community first increased and then decreased. Responsive actions toward influenza varied. Most respondents took actions that required little extra effort, such as ventilating rooms; these actions did not change over time. Comparatively, a smaller number of respondents took actions for coping with influenza, such as vaccination; however, these actions were taken by an increasing number of respondents over time. The association between risk perception and behavior was unstable. Positive, insignificant, and negative associations were obtained in the three surveys. In conclusion, the evolving patterns of risk perception and responsive behavior over the course of an influenza pandemic are sensitive to how risk and behavior are defined and scoped.",2015 Dec 14,"['Xu, Jianhua', 'Peng, Zongchao']",PLoS One,,,True
ff986fb85af07d524411d6eb829e38be349df839,PMC,Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease,http://dx.doi.org/10.1371/journal.pone.0144865,PMC4682845,26658006,CC BY,"BACKGROUND: A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1(st) October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. METHODS AND RESULTS: The crystal structure of MERS-CoV M(pro) indicates that it shares a similar scaffold to that of other coronaviral M(pro) and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M(pro) undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M(pro) is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. CONCLUSIONS: MERS-CoV M(pro) shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M(pro) family.",2015 Dec 14,"['Ho, Bo-Lin', 'Cheng, Shu-Chun', 'Shi, Lin', 'Wang, Ting-Yun', 'Ho, Kuan-I', 'Chou, Chi-Yuan']",PLoS One,,,True
ae6f4f9bdd17413b0378597482f695394c48d599,PMC,Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease,http://dx.doi.org/10.1371/journal.pone.0144865,PMC4682845,26658006,CC BY,"BACKGROUND: A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1(st) October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. METHODS AND RESULTS: The crystal structure of MERS-CoV M(pro) indicates that it shares a similar scaffold to that of other coronaviral M(pro) and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M(pro) undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M(pro) is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. CONCLUSIONS: MERS-CoV M(pro) shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M(pro) family.",2015 Dec 14,"['Ho, Bo-Lin', 'Cheng, Shu-Chun', 'Shi, Lin', 'Wang, Ting-Yun', 'Ho, Kuan-I', 'Chou, Chi-Yuan']",PLoS One,,,False
791960717d653a8c50cefae61dd7390fed9a2af3,PMC,Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease,http://dx.doi.org/10.1371/journal.pone.0144865,PMC4682845,26658006,CC BY,"BACKGROUND: A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1(st) October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. METHODS AND RESULTS: The crystal structure of MERS-CoV M(pro) indicates that it shares a similar scaffold to that of other coronaviral M(pro) and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M(pro) undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M(pro) is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. CONCLUSIONS: MERS-CoV M(pro) shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M(pro) family.",2015 Dec 14,"['Ho, Bo-Lin', 'Cheng, Shu-Chun', 'Shi, Lin', 'Wang, Ting-Yun', 'Ho, Kuan-I', 'Chou, Chi-Yuan']",PLoS One,,,False
c38b3a8cc344708e05fd6e696cb2f05372c45fbe,PMC,Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease,http://dx.doi.org/10.1371/journal.pone.0144865,PMC4682845,26658006,CC BY,"BACKGROUND: A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1(st) October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. METHODS AND RESULTS: The crystal structure of MERS-CoV M(pro) indicates that it shares a similar scaffold to that of other coronaviral M(pro) and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M(pro) undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M(pro) is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. CONCLUSIONS: MERS-CoV M(pro) shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M(pro) family.",2015 Dec 14,"['Ho, Bo-Lin', 'Cheng, Shu-Chun', 'Shi, Lin', 'Wang, Ting-Yun', 'Ho, Kuan-I', 'Chou, Chi-Yuan']",PLoS One,,,False
fa4e07fc8a5200929c2299116a7784db01fafed0,PMC,Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease,http://dx.doi.org/10.1371/journal.pone.0144865,PMC4682845,26658006,CC BY,"BACKGROUND: A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1(st) October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. METHODS AND RESULTS: The crystal structure of MERS-CoV M(pro) indicates that it shares a similar scaffold to that of other coronaviral M(pro) and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M(pro) undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M(pro) is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. CONCLUSIONS: MERS-CoV M(pro) shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M(pro) family.",2015 Dec 14,"['Ho, Bo-Lin', 'Cheng, Shu-Chun', 'Shi, Lin', 'Wang, Ting-Yun', 'Ho, Kuan-I', 'Chou, Chi-Yuan']",PLoS One,,,False
ac2ef63ed042c4a98bd5d61a5a65ac535705a49f,PMC,Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease,http://dx.doi.org/10.1371/journal.pone.0144865,PMC4682845,26658006,CC BY,"BACKGROUND: A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1(st) October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. METHODS AND RESULTS: The crystal structure of MERS-CoV M(pro) indicates that it shares a similar scaffold to that of other coronaviral M(pro) and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M(pro) undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M(pro) is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. CONCLUSIONS: MERS-CoV M(pro) shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M(pro) family.",2015 Dec 14,"['Ho, Bo-Lin', 'Cheng, Shu-Chun', 'Shi, Lin', 'Wang, Ting-Yun', 'Ho, Kuan-I', 'Chou, Chi-Yuan']",PLoS One,,,False
99eb640f565313af87f99b81f438b833002ba272,PMC,Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease,http://dx.doi.org/10.1371/journal.pone.0144865,PMC4682845,26658006,CC BY,"BACKGROUND: A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1(st) October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. METHODS AND RESULTS: The crystal structure of MERS-CoV M(pro) indicates that it shares a similar scaffold to that of other coronaviral M(pro) and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M(pro) undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M(pro) is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. CONCLUSIONS: MERS-CoV M(pro) shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M(pro) family.",2015 Dec 14,"['Ho, Bo-Lin', 'Cheng, Shu-Chun', 'Shi, Lin', 'Wang, Ting-Yun', 'Ho, Kuan-I', 'Chou, Chi-Yuan']",PLoS One,,,False
73962bb05d0fa45657756857801fbb3f9e139b04,PMC,TGF-βI Regulates Cell Migration through Pluripotent Transcription Factor OCT4 in Endometriosis,http://dx.doi.org/10.1371/journal.pone.0145256,PMC4682958,26675296,CC BY,"Transforming growth factor (TGF-β)/TGF-β receptor signal is known to promote cell migration. Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-β/TGF-β receptor and OCT4 affect endometriotic cell migration still remain largely unknown. Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls. We found the mRNA levels of TGF-β receptor I (TGF-β RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low-migratory normal or hyperplastic endometrium. Positive correlations between TGF-β RI and OCT4, and either TGF-β RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues. TGF-βI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-βI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A. Furthermore, TGF-βI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-βI-induced cell migration activity evidenced by wound-closure assay, transwell assay, and confocal image of F-actin cellular distribution. In conclusion, the present findings demonstrate that the niche TGF-β plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell migration. These findings would be useful for developing therapeutic strategies targeting TGF-β-OCT4 signaling to prevent endometriosis in the future.",2015 Dec 16,"['Au, Heng-Kien', 'Chang, Jui-Hung', 'Wu, Yu-Chih', 'Kuo, Yung-Che', 'Chen, Yu-Hsi', 'Lee, Wei-Chin', 'Chang, Te-Sheng', 'Lan, Pei-Chi', 'Kuo, Hung-Chih', 'Lee, Kha-Liang', 'Lee, Mei-Tsu', 'Tzeng, Chii-Ruey', 'Huang, Yen-Hua']",PLoS One,,,True
805edd3fe7b8a903e0c308d2d70a941e5d8e00fd,PMC,TGF-βI Regulates Cell Migration through Pluripotent Transcription Factor OCT4 in Endometriosis,http://dx.doi.org/10.1371/journal.pone.0145256,PMC4682958,26675296,CC BY,"Transforming growth factor (TGF-β)/TGF-β receptor signal is known to promote cell migration. Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-β/TGF-β receptor and OCT4 affect endometriotic cell migration still remain largely unknown. Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls. We found the mRNA levels of TGF-β receptor I (TGF-β RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low-migratory normal or hyperplastic endometrium. Positive correlations between TGF-β RI and OCT4, and either TGF-β RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues. TGF-βI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-βI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A. Furthermore, TGF-βI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-βI-induced cell migration activity evidenced by wound-closure assay, transwell assay, and confocal image of F-actin cellular distribution. In conclusion, the present findings demonstrate that the niche TGF-β plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell migration. These findings would be useful for developing therapeutic strategies targeting TGF-β-OCT4 signaling to prevent endometriosis in the future.",2015 Dec 16,"['Au, Heng-Kien', 'Chang, Jui-Hung', 'Wu, Yu-Chih', 'Kuo, Yung-Che', 'Chen, Yu-Hsi', 'Lee, Wei-Chin', 'Chang, Te-Sheng', 'Lan, Pei-Chi', 'Kuo, Hung-Chih', 'Lee, Kha-Liang', 'Lee, Mei-Tsu', 'Tzeng, Chii-Ruey', 'Huang, Yen-Hua']",PLoS One,,,False
498b458b57e491d5af55dc351d3c11f8bc437bb0,PMC,TGF-βI Regulates Cell Migration through Pluripotent Transcription Factor OCT4 in Endometriosis,http://dx.doi.org/10.1371/journal.pone.0145256,PMC4682958,26675296,CC BY,"Transforming growth factor (TGF-β)/TGF-β receptor signal is known to promote cell migration. Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-β/TGF-β receptor and OCT4 affect endometriotic cell migration still remain largely unknown. Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls. We found the mRNA levels of TGF-β receptor I (TGF-β RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low-migratory normal or hyperplastic endometrium. Positive correlations between TGF-β RI and OCT4, and either TGF-β RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues. TGF-βI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-βI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A. Furthermore, TGF-βI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-βI-induced cell migration activity evidenced by wound-closure assay, transwell assay, and confocal image of F-actin cellular distribution. In conclusion, the present findings demonstrate that the niche TGF-β plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell migration. These findings would be useful for developing therapeutic strategies targeting TGF-β-OCT4 signaling to prevent endometriosis in the future.",2015 Dec 16,"['Au, Heng-Kien', 'Chang, Jui-Hung', 'Wu, Yu-Chih', 'Kuo, Yung-Che', 'Chen, Yu-Hsi', 'Lee, Wei-Chin', 'Chang, Te-Sheng', 'Lan, Pei-Chi', 'Kuo, Hung-Chih', 'Lee, Kha-Liang', 'Lee, Mei-Tsu', 'Tzeng, Chii-Ruey', 'Huang, Yen-Hua']",PLoS One,,,False
713fce03f461b2c103732cff207a5de11bb69125,PMC,TGF-βI Regulates Cell Migration through Pluripotent Transcription Factor OCT4 in Endometriosis,http://dx.doi.org/10.1371/journal.pone.0145256,PMC4682958,26675296,CC BY,"Transforming growth factor (TGF-β)/TGF-β receptor signal is known to promote cell migration. Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-β/TGF-β receptor and OCT4 affect endometriotic cell migration still remain largely unknown. Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls. We found the mRNA levels of TGF-β receptor I (TGF-β RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low-migratory normal or hyperplastic endometrium. Positive correlations between TGF-β RI and OCT4, and either TGF-β RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues. TGF-βI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-βI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A. Furthermore, TGF-βI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-βI-induced cell migration activity evidenced by wound-closure assay, transwell assay, and confocal image of F-actin cellular distribution. In conclusion, the present findings demonstrate that the niche TGF-β plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell migration. These findings would be useful for developing therapeutic strategies targeting TGF-β-OCT4 signaling to prevent endometriosis in the future.",2015 Dec 16,"['Au, Heng-Kien', 'Chang, Jui-Hung', 'Wu, Yu-Chih', 'Kuo, Yung-Che', 'Chen, Yu-Hsi', 'Lee, Wei-Chin', 'Chang, Te-Sheng', 'Lan, Pei-Chi', 'Kuo, Hung-Chih', 'Lee, Kha-Liang', 'Lee, Mei-Tsu', 'Tzeng, Chii-Ruey', 'Huang, Yen-Hua']",PLoS One,,,False
1dcfe803d2660b1fdfa8006aace78d485512e156,PMC,"Structural and Functional Insights into Small, Glutamine-Rich, Tetratricopeptide Repeat Protein Alpha",http://dx.doi.org/10.3389/fmolb.2015.00071,PMC4683186,26734616,CC BY,"The small glutamine-rich, tetratricopeptide repeat-containing protein alpha (SGTA) is an emerging player in the quality control of secretory and membrane proteins mislocalized to the cytosol, with established roles in tail-anchored (TA) membrane protein biogenesis. SGTA consists of three structural domains with individual functions, an N-terminal dimerization domain that assists protein sorting pathways, a central tetratricopeptide repeat (TPR) domain that mediates interactions with heat-shock proteins, proteasomal, and hormonal receptors, and viral proteins, and a C-terminal glutamine rich region that binds hydrophobic substrates. SGTA has been linked to viral lifecycles and hormone receptor signaling, with implications in the pathogenesis of various disease states. Thus far, a range of biophysical techniques have been employed to characterize SGTA structure in some detail, and to investigate its interactions with binding partners in different biological contexts. A complete description of SGTA structure, together with further investigation into its function as a co-chaperone involved quality control, could provide us with useful insights into its role in maintaining cellular proteostasis, and broaden our understanding of mechanisms underlying associated pathologies. This review describes how some structural features of SGTA have been elucidated, and what this has uncovered about its cellular functions. A brief background on the structure and function of SGTA is given, highlighting its importance to biomedicine and related fields. The current level of knowledge and what remains to be understood about the structure and function of SGTA is summarized, discussing the potential direction of future research.",2015 Dec 18,"['Roberts, Joanna D.', 'Thapaliya, Arjun', 'Martínez-Lumbreras, Santiago', 'Krysztofinska, Ewelina M.', 'Isaacson, Rivka L.']",Front Mol Biosci,,,True
963cc6ca5e9eecf735dfcb89e2320a22fa4bcec6,PMC,Complete Genome Sequence of the Porcine Epidemic Diarrhea Virus Variant CH/HNYF/2014,http://dx.doi.org/10.1128/genomeA.01486-15,PMC4683238,26679593,CC BY,"Sow’s milk is a potential route for the vertical transmission of porcine epidemic diarrhea virus (PEDV) from sow to suckling piglet. We report here the complete genome sequence of PEDV strain CH/HNYF/2014, which was isolated from milk samples. This information provides further understanding of the transmission mechanisms and genetic diversity of PEDV.",2015 Dec 17,"['Li, Renfeng', 'Tian, Xiangqin', 'Qiao, Songlin', 'Guo, Junqing', 'Xie, Weitao', 'Zhang, Gaiping']",Genome Announc,,,True
85bf8bcd3494765f259e8903ed153dff0ff40a4f,PMC,TMV mutants with poly(A) tracts of different lengths demonstrate structural variations in 3′UTR affecting viral RNAs accumulation and symptom expression,http://dx.doi.org/10.1038/srep18412,PMC4683447,26678425,CC BY,"The upstream pseudoknots domain (UPD) of Tobacco mosaic virus (TMV) is located at the 3′-untranslated region (UTR). It plays an important role in virus replication and translation. To determine the importance of UPD and 3′-UTR, and the effects of introduced RNA elements in TMV 3′-UTR, a series of TMV mutants with internal poly(A) tract upstream of UPD was constructed for structural analysis by selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE). TMV(24A+UPD) and TMV(42A+UPD) formed a similar structure as that of TMV 3′-UTR, but TMV(62A+UPD) structures altered by the introduced poly(A) tract. In addition, TMV(24A+UPD) had a higher viral RNAs accumulation than TMV in N. benthamiana protoplasts, and induced lethal symptoms in the infected plants. TMV(62A+UPD) showed a drastically reduced accumulation, its coat protein was undetectable in protoplasts, and the inoculated plants remained symptomless. This study analyzed the structures of 3′-UTR of TMV and found that the longer poly(A) tract introduced upstream of UPD reduced viral RNAs accumulation and induced milder symptoms in N. benthamiana. In conclusion, different lengths of the internal poly(A) tract introduced into the TMV 3′UTR lead to structural variations that affect virus accumulation and symptom expression.",2015 Dec 18,"['Guo, Song', 'Kierzek, Elzbieta', 'Chen, Gang', 'Zhou, Yi-Jun', 'Wong, Sek-Man']",Sci Rep,,,True
30c28ceb7614a39d2950cb866b82a062254333cc,PMC,TMV mutants with poly(A) tracts of different lengths demonstrate structural variations in 3′UTR affecting viral RNAs accumulation and symptom expression,http://dx.doi.org/10.1038/srep18412,PMC4683447,26678425,CC BY,"The upstream pseudoknots domain (UPD) of Tobacco mosaic virus (TMV) is located at the 3′-untranslated region (UTR). It plays an important role in virus replication and translation. To determine the importance of UPD and 3′-UTR, and the effects of introduced RNA elements in TMV 3′-UTR, a series of TMV mutants with internal poly(A) tract upstream of UPD was constructed for structural analysis by selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE). TMV(24A+UPD) and TMV(42A+UPD) formed a similar structure as that of TMV 3′-UTR, but TMV(62A+UPD) structures altered by the introduced poly(A) tract. In addition, TMV(24A+UPD) had a higher viral RNAs accumulation than TMV in N. benthamiana protoplasts, and induced lethal symptoms in the infected plants. TMV(62A+UPD) showed a drastically reduced accumulation, its coat protein was undetectable in protoplasts, and the inoculated plants remained symptomless. This study analyzed the structures of 3′-UTR of TMV and found that the longer poly(A) tract introduced upstream of UPD reduced viral RNAs accumulation and induced milder symptoms in N. benthamiana. In conclusion, different lengths of the internal poly(A) tract introduced into the TMV 3′UTR lead to structural variations that affect virus accumulation and symptom expression.",2015 Dec 18,"['Guo, Song', 'Kierzek, Elzbieta', 'Chen, Gang', 'Zhou, Yi-Jun', 'Wong, Sek-Man']",Sci Rep,,,False
405b2a0699c55c52df71d3a52c454486e2f3ad1c,PMC,"Continued high incidence of children with severe influenza A(H1N1)pdm09 admitted to paediatric intensive care units in Germany during the first three post-pandemic influenza seasons, 2010/11–2012/13",http://dx.doi.org/10.1186/s12879-015-1293-1,PMC4683816,26678835,CC BY,"BACKGROUND: Previous influenza surveillance at paediatric intensive care units (PICUs) in Germany indicated increased incidence of PICU admissions for the pandemic influenza subtype A(H1N1)pdm09. We investigated incidence and clinical characteristics of influenza in children admitted to PICUs during the first three post-pandemic influenza seasons, using active screening. METHODS: We conducted a prospective surveillance study in 24 PICUs in Bavaria (Germany) from October 2010 to September 2013. Influenza cases among children between 1 month and 16 years of age admitted to these PICUs with acute respiratory infection were confirmed by PCR analysis of respiratory secretions. RESULTS: A total of 24/7/20 influenza-associated PICU admissions were recorded in the post-pandemic seasons 1/2/3; incidence estimates per 100,000 children were 1.72/0.76/1.80, respectively. Of all 51 patients, 80 % had influenza A, including 65 % with A(H1N1)pdm09. Influenza A(H1N1)pdm09 was almost absent in season 2 (incidence 0.11), but dominated PICU admissions in seasons 1 (incidence 1.35) and 3 (incidence 1.17). Clinical data was available for 47 influenza patients; median age was 4.8 years (IQR 1.6–11.0). The most frequent diagnoses were influenza-associated pneumonia (62 %), bronchitis/bronchiolitis (32 %), secondary bacterial pneumonia (26 %), and ARDS (21 %). Thirty-six patients (77 %) had underlying medical conditions. Median duration of PICU stay was 3 days (IQR 1–11). Forty-seven per cent of patients received mechanical ventilation, and one patient (2 %) extracorporeal membrane oxygenation; 19 % were treated with oseltamivir. Five children (11 %) had pulmonary sequelae. Five children (11 %) died; all had underlying chronic conditions and were infected with A(H1N1)pdm09. In season 3, patients with A(H1N1)pdm09 were younger than in season 1 (p = 0.020), were diagnosed more often with bronchitis/bronchiolitis (p = 0.004), and were admitted to a PICU later after the onset of influenza symptoms (p = 0.041). CONCLUSIONS: Active screening showed a continued high incidence of A(H1N1)pdm09-associated PICU admissions in the post-pandemic seasons 1 and 3, and indicated possible underestimation of incidence in previous German studies. The age shift of severe A(H1N1)pdm09 towards younger children may be explained by increasing immunity in the older paediatric population. The high proportion of patients with underlying chronic conditions indicates the importance of consistent implementation of the current influenza vaccination recommendations for risk groups in Germany.",2015 Dec 18,"['Streng, Andrea', 'Prifert, Christiane', 'Weissbrich, Benedikt', 'Liese, Johannes G.', None]",BMC Infect Dis,,,True
eb5417b7729ff5548e5b9ddcb837fa52efc586f8,PMC,In silico target fishing and pharmacological profiling for the isoquinoline alkaloids of Macleayacordata (Bo Luo Hui),http://dx.doi.org/10.1186/s13020-015-0067-4,PMC4683977,26691584,CC BY,"BACKGROUND: Some isoquinoline alkaloids from Macleaya cordata (Willd). R. Br. (Bo Luo Hui) exhibited antibacterial, antiparasitic, antitumor, and analgesic effects. The targets of these isoquinoline alkaloids are undefined. This study aims to investigate the compound–target interaction network and potential pharmacological actions of isoquinoline alkaloids of M. cordata by reverse pharmacophore database screening. METHODS: The targets of 26 isoquinoline alkaloids identified from M. cordata were predicted by a pharmacophore-based target fishing approach. Discovery Studio 3.5 and two pharmacophore databases (PharmaDB and HypoDB) were employed for the target profiling. A compound–target interaction network of M. cordata was constructed and analyzed by Cytoscape 3.0. RESULTS: Thirteen of the 65 predicted targets identified by PharmaDB were confirmed as targets by HypoDB screening. The targets in the interaction network of M. cordata were involved in cancer (31 targets), microorganisms (12 targets), neurodegeneration (10 targets), inflammation and autoimmunity (8 targets), parasitosis (5 targets), injury (4 targets), and pain (3 targets). Dihydrochelerythrine (C6) was found to hit 23 fitting targets. Macrophage migration inhibitory factor (MIF) hits 15 alkaloids (C1–2, C11–16, C19–25) was the most promising target related to cancer. CONCLUSION: Through in silico target fishing, the anticancer, anti-inflammatory, and analgesic effects of M. cordata were the most significant among many possible activities. The possible anticancer effects were mainly contributed by the isoquinoline alkaloids as active components.",2015 Dec 17,"['Lei, Qifang', 'Liu, Haibo', 'Peng, Yong', 'Xiao, Peigen']",Chin Med,,,True
25397e5a50461221e9a0706147a6b6e3ad449ac9,PMC,MERS-CoV geography and ecology in the Middle East: analyses of reported camel exposures and a preliminary risk map,http://dx.doi.org/10.1186/s13104-015-1789-1,PMC4684610,26683322,CC BY,"BACKGROUND: Middle Eastern respiratory syndrome coronavirus (MERS-CoV) has spread rapidly across much of the Middle East, but no quantitative mapping of transmission risk has been developed to date. Moreover, details of the transmission cycle of the virus remain unclear, particularly regarding the role of camels as a reservoir host for human infections. METHODS: We present a first analysis of the environmental circumstances under which MERS-CoV cases have occurred in the Middle East, covering all case occurrences through May 2015, using ecological niche modeling approaches to map transmission risk. We compare the environmental breadth of conditions under which cases have reported camel contacts with that of the broader population of all cases, to assess whether camel-associated cases occur under a more restricted set of environmental circumstances. RESULTS: We documented geographic and environmental distributions of MERS-CoV cases across the Middle East, and offer preliminary mapping of transmission risk. We confirm the idea that climatic dimensions of camel-associated cases are more constrained and less variable than the broader suite of case occurrences; hence, camel exposure may be a key limiting element in MERS-CoV transmission. CONCLUSION: This study offers a first detailed geographic and environmental analysis of MERS-CoV distributions across the Middle East. Results indicated that camel-exposed cases occur under a narrower suite of environmental conditions than non-camel-exposed cases, suggesting perhaps a key role for camels in the transmission of the disease, and perhaps a narrower area of risk for ‘primary,’ camel-derived cases of MERS.",2015 Dec 18,"['Reeves, Tarian', 'Samy, Abdallah M.', 'Peterson, A. Townsend']",BMC Res Notes,,,True
f28c1e92be3354c2df1cb282177ef962c3b5c9c6,PMC,Strategies for Pharmacological Organoprotection during Extracorporeal Circulation Targeting Ischemia-Reperfusion Injury,http://dx.doi.org/10.3389/fphar.2015.00296,PMC4686733,26733868,CC BY,"Surgical correction of congenital cardiac malformations or aortocoronary bypass surgery in many cases implies the use of cardiopulmonary-bypass (CPB). However, a possible negative impact of CPB on internal organs such as brain, kidney, lung and liver cannot be neglected. In general, CPB initiates a systemic inflammatory response (SIRS) which is presumably caused by contact of blood components with the surface of CPB tubing. Moreover, during CPB the heart typically undergoes a period of cold ischemia, and the other peripheral organs a global low flow hypoperfusion. As a result, a plethora of pro-inflammatory mediators and cytokines is released activating different biochemical pathways, which finally may result in the occurrence of microthrombosis, microemboli, in depletion of coagulation factors and haemorrhagic diathesis besides typical ischemia-reperfusion injuries. In our review we will focus on possible pharmacological interventions in patients to decrease negative effects of CPB and to improve post-operative outcome with regard to heart and other organs like brain, kidney, or lung.",2015 Dec 22,"['Salameh, Aida', 'Dhein, Stefan']",Front Pharmacol,,,True
575faff450d20d0f359d000ebc8b66b638094613,PMC,Gliopathy of Demyelinating and Non-Demyelinating Strains of Mouse Hepatitis Virus,http://dx.doi.org/10.3389/fncel.2015.00488,PMC4686739,26733813,CC BY,"Demyelination in the central nervous system induced by neurovirulent strains of Mouse Hepatitis Virus (MHV) is mediated by the viral spike glycoprotein, but it is not clear whether the mechanism of this disease pathology involves direct viral infection of oligodendrocytes. Detailed studies of glial cell tropism of MHV are presented, demonstrating that direct MHV infection of oligodendrocytes differs between demyelinating (RSA59) and non-demyelinating (RSMHV2) viral strains both in vitro and in vivo. Our results indicate that direct injury of mature oligodendrocytes is an important mechanism of virus-induced demyelination. In vivo, RSA59 infection was identified in spinal cord gray and white matter, but infected oligodendrocytes were restricted to white matter. In contrast, RSMHV2 infection was restricted to gray matter neurons and was not localized to oligodendrocytes. In vitro, RSA59 can infect both oligodendrocyte precursors and differentiated oligodendrocytes, whereas RSMHV2 can infect oligodendrocyte precursors but not differentiated oligodendrocytes. Viral spreading through axonal means to white matter and release of the demyelinating strain MHV at the nerve end is critical for oligodendrocytes infection and subsequent demyelination. Understanding the mechanisms by which known viruses effect demyelination in this animal model has important therapeutic implications in the treatment of human demyelinating disease.",2015 Dec 22,"['Kenyon, Lawrence C.', 'Biswas, Kaushiki', 'Shindler, Kenneth S.', 'Nabar, Manasi', 'Stout, Marjorie', 'Hingley, Susan T.', 'Grinspan, Judith B.', 'Das Sarma, Jayasri']",Front Cell Neurosci,,,True
27ea5838cb5cf114ddeecd9972be98813834ef9c,PMC,Risk Distribution of Human Infections with Avian Influenza H7N9 and H5N1 virus in China,http://dx.doi.org/10.1038/srep18610,PMC4686887,26691585,CC BY,"It has been documented that the epidemiological characteristics of human infections with H7N9 differ significantly between H5N1. However, potential factors that may explain the different spatial distributions remain unexplored. We use boosted regression tree (BRT) models to explore the association of agro-ecological, environmental and meteorological variables with the occurrence of human cases of H7N9 and H5N1, and map the probabilities of occurrence of human cases. Live poultry markets, density of human, coverage of built-up land, relative humidity and precipitation were significant predictors for both. In addition, density of poultry, coverage of shrub and temperature played important roles for human H7N9 infection, whereas human H5N1 infection was associated with coverage of forest and water body. Based on the risks and distribution of ecological characteristics which may facilitate the circulation of the two viruses, we found Yangtze River Delta and Pearl River Delta, along with a few spots on the southeast coastline, to be the high risk areas for H7N9 and H5N1. Additional, H5N1 risk spots were identified in eastern Sichuan and southern Yunnan Provinces. Surveillance of the two viruses needs to be enhanced in these high risk areas to reduce the risk of future epidemics of avian influenza in China.",2015 Dec 22,"['Li, Xin-Lou', 'Yang, Yang', 'Sun, Ye', 'Chen, Wan-Jun', 'Sun, Ruo-Xi', 'Liu, Kun', 'Ma, Mai-Juan', 'Liang, Song', 'Yao, Hong-Wu', 'Gray, Gregory C.', 'Fang, Li-Qun', 'Cao, Wu-Chun']",Sci Rep,,,True
67466fd44aa1843c57174386e917578f0d83d71a,PMC,Modeling the Transmission of Middle East Respirator Syndrome Corona Virus in the Republic of Korea,http://dx.doi.org/10.1371/journal.pone.0144778,PMC4686901,26690750,CC BY,"The 2015 epidemic of Middle East respiratory syndrome (MERS) in the Republic of Korea has been the largest outbreak outside Middle East. This epidemic had caused 185 laboratory-confirmed cases and 36 deaths in the Republic of Korea until September 2, 2015, which attracted public’s attention. Based on the detailed data of patients released by World Health Organization (WHO) and actual propagation of the epidemic, we construct two dynamical models to simulate the propagation processes from May 20 to June 8 and from June 9 to July 10, 2015, respectively and find that the basic reproduction number R (0) reaches up to 4.422. The numerical analysis shows that the reasons of the outbreak spread quickly are lack of self-protection sense and targeted control measures. Through partial correction analysis, the parameters β (1) and γ have strong correlations with R (0), i.e., the infectivity and proportion of the asymptomatic infected cases have much influence on the spread of disease. By sensitivity analysis, strengthening self-protection ability of susceptible and quickly isolating or monitoring close contacts are effective measures to control the disease.",2015 Dec 21,"['Xia, Zhi-Qiang', 'Zhang, Juan', 'Xue, Ya-Kui', 'Sun, Gui-Quan', 'Jin, Zhen']",PLoS One,,,True
40640676ca5aecdde3a40feb137cc3049c14faef,PMC,Modeling the Transmission of Middle East Respirator Syndrome Corona Virus in the Republic of Korea,http://dx.doi.org/10.1371/journal.pone.0144778,PMC4686901,26690750,CC BY,"The 2015 epidemic of Middle East respiratory syndrome (MERS) in the Republic of Korea has been the largest outbreak outside Middle East. This epidemic had caused 185 laboratory-confirmed cases and 36 deaths in the Republic of Korea until September 2, 2015, which attracted public’s attention. Based on the detailed data of patients released by World Health Organization (WHO) and actual propagation of the epidemic, we construct two dynamical models to simulate the propagation processes from May 20 to June 8 and from June 9 to July 10, 2015, respectively and find that the basic reproduction number R (0) reaches up to 4.422. The numerical analysis shows that the reasons of the outbreak spread quickly are lack of self-protection sense and targeted control measures. Through partial correction analysis, the parameters β (1) and γ have strong correlations with R (0), i.e., the infectivity and proportion of the asymptomatic infected cases have much influence on the spread of disease. By sensitivity analysis, strengthening self-protection ability of susceptible and quickly isolating or monitoring close contacts are effective measures to control the disease.",2015 Dec 21,"['Xia, Zhi-Qiang', 'Zhang, Juan', 'Xue, Ya-Kui', 'Sun, Gui-Quan', 'Jin, Zhen']",PLoS One,,,True
abd80dcf360dafb7c921416daedc2021908c3503,PMC,Coronaviruses: emerging and re-emerging pathogens in humans and animals,http://dx.doi.org/10.1186/s12985-015-0432-z,PMC4687117,26690088,CC BY,"The severe acute respiratory syndrome coronavirus (SARS-CoV) and recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) epidemics have proven the ability of coronaviruses to cross species barrier and emerge rapidly in humans. Other coronaviruses such as porcine epidemic diarrhea virus (PEDV) are also known to cause major disease epidemics in animals wiith huge economic loss. This special issue in Virology Journal aims to highlight the advances and key discoveries in the animal origin, viral evolution, epidemiology, diagnostics and pathogenesis of the emerging and re-emerging coronaviruses in both humans and animals.",2015 Dec 22,"['Lau, Susanna K. P.', 'Chan, Jasper F. W.']",Virol J,,,True
a63f9b0555e4ec19bb5a38d4e4f282ed9bbb8612,PMC,Non-coding yet non-trivial: a review on the computational genomics of lincRNAs,http://dx.doi.org/10.1186/s13040-015-0075-z,PMC4687140,26697116,CC BY,"Long intergenic non-coding RNAs (lincRNAs) represent one of the most mysterious RNA species encoded by the human genome. Thanks to next generation sequencing (NGS) technology and its applications, we have recently witnessed a surge in non-coding RNA research, including lincRNA research. Here, we summarize the recent advancement in genomics studies of lincRNAs. We review the emerging characteristics of lincRNAs, the experimental and computational approaches to identify lincRNAs, their known mechanisms of regulation, the computational methods and resources for lincRNA functional predictions, and discuss the challenges to understanding lincRNA comprehensively.",2015 Dec 22,"['Ching, Travers', 'Masaki, Jayson', 'Weirather, Jason', 'Garmire, Lana X.']",BioData Min,,,True
12f712c348c26e092759d804778defe2d2d4af6f,PMC,Middle East respiratory syndrome coronavirus infection: virus-host cell interactions and implications on pathogenesis,http://dx.doi.org/10.1186/s12985-015-0446-6,PMC4687146,26690369,CC BY,"Middle-East Respiratory Syndrome coronavirus (MERS-CoV) was identified to cause severe respiratory infection in humans since 2012. The continuing MERS epidemic with a case-fatality of more than 30 % poses a major threat to public health worldwide. Currently, the pathogenesis of human MERS-CoV infection remains poorly understood. We reviewed experimental findings from human primary cells and ex vivo human lung tissues, as well as those from animal studies, so as to understand the pathogenesis and high case-fatality of MERS. Human respiratory epithelial cells are highly susceptible to MERS-CoV and can support productive viral replication. However, the induction of antiviral cytokines and proinflammatory cytokines/chemokines are substantially dampened in the infected epithelial cells, due to the antagonistic mechanisms evolved by the virus. MERS-CoV can readily infect and robustly replicate in human macrophages and dendritic cells, triggering the aberrant production of proinflammatory cytokines/chemokines. MERS-CoV can also effectively infect human primary T cells and induce massive apoptosis in these cells. Although data from clinical, in vitro and ex vivo studies suggested the potential for virus dissemination, extrapulmonary involvement in MERS patients has not been ascertained due to the lack of autopsy study. In MERS-CoV permissive animal models, although viral RNA can be detected from multiple organs of the affected animals, the brain of human DPP4-transgenic mouse was the only extrapulmonary organ from which the infectious virus can be recovered. More research findings on the pathogenesis of MERS and the tissue tropisms of MERS-CoV may help to improve the treatment and infection control of MERS.",2015 Dec 22,"['Zhou, Jie', 'Chu, Hin', 'Chan, Jasper Fuk-Woo', 'Yuen, Kwok-Yung']",Virol J,,,True
a672930b5dc73b6002ca4a697e2109b130dee042,PMC,Porcine epidemic diarrhea virus: An emerging and re-emerging epizootic swine virus,http://dx.doi.org/10.1186/s12985-015-0421-2,PMC4687282,26689811,CC BY,"The enteric disease of swine recognized in the early 1970s in Europe was initially described as “epidemic viral diarrhea” and is now termed “porcine epidemic diarrhea (PED)”. The coronavirus referred to as PED virus (PEDV) was determined to be the etiologic agent of this disease in the late 1970s. Since then the disease has been reported in Europe and Asia, but the most severe outbreaks have occurred predominantly in Asian swine-producing countries. Most recently, PED first emerged in early 2013 in the United States that caused high morbidity and mortality associated with PED, remarkably affecting US pig production, and spread further to Canada and Mexico. Soon thereafter, large-scale PED epidemics recurred through the pork industry in South Korea, Japan, and Taiwan. These recent outbreaks and global re-emergence of PED require urgent attention and deeper understanding of PEDV biology and pathogenic mechanisms. This paper highlights the current knowledge of molecular epidemiology, diagnosis, and pathogenesis of PEDV, as well as prevention and control measures against PEDV infection. More information about the virus and the disease is still necessary for the development of effective vaccines and control strategies. It is hoped that this review will stimulate further basic and applied studies and encourage collaboration among producers, researchers, and swine veterinarians to provide answers that improve our understanding of PEDV and PED in an effort to eliminate this economically significant viral disease, which emerged or re-emerged worldwide.",2015 Dec 22,"Lee, Changhee",Virol J,,,True
f1570e2dfd60e3bc423fede19c89171ac06da885,PMC,Retroviral DNA—the silent winner: blood transfusion containing latent feline leukemia provirus causes infection and disease in naïve recipient cats,http://dx.doi.org/10.1186/s12977-015-0231-z,PMC4687292,26689419,CC BY,"BACKGROUND: The feline leukemia virus (FeLV) is a gamma-retrovirus of domestic cats that was discovered half a century ago. Cats that are infected with FeLV may develop a progressive infection resulting in persistent viremia, immunodeficiency, tumors, anemia and death. A significant number of cats mount a protective immune response that suppresses viremia; these cats develop a regressive infection characterized by the absence of viral replication and the presence of low levels of proviral DNA. The biological importance of these latter provirus carriers is largely unknown. RESULTS: Here, we demonstrate that ten cats that received a transfusion of blood from aviremic provirus carriers developed active FeLV infections, some with a progressive outcome and the development of fatal FeLV-associated disease. The infection outcome, disease spectrum and evolution into FeLV-C in one cat mirrored those of natural infection. Two cats developed persistent antigenemia; six cats were transiently antigenemic. Reactivation of infection occurred in some cats. One recipient developed non-regenerative anemia associated with FeLV-C, and four others developed a T-cell lymphoma, one with secondary lymphoblastic leukemia. Five of the ten recipient cats received provirus-positive aviremic blood, whereas the other five received provirus- and viral RNA-positive but aviremic blood. Notably, the cats that received blood containing only proviral DNA exhibited a later onset but graver outcome of FeLV infection than the cats that were transfused with blood containing proviral DNA and viral RNA. Leukocyte counts and cytokine analyses indicated that the immune system of the latter cats reacted quicker and more efficiently. CONCLUSIONS: Our results underline the biological and epidemiological relevance of FeLV provirus carriers and the risk of inadvertent FeLV transmission via blood transfusion and demonstrate the replication capacity of proviral DNA if uncontrolled by the immune system. Our results have implications not only for veterinary medicine, such as the requirement for testing blood donors and blood products for FeLV provirus by sensitive polymerase chain reaction, but are also of general interest by revealing the importance of latent retroviral DNA in infected hosts. When aiming to eliminate a retroviral infection from a population, provirus carriers must be considered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-015-0231-z) contains supplementary material, which is available to authorized users.",2015 Dec 21,"['Nesina, Stefanie', 'Katrin Helfer-Hungerbuehler, A.', 'Riond, Barbara', 'Boretti, Felicitas S.', 'Willi, Barbara', 'Meli, Marina L.', 'Grest, Paula', 'Hofmann-Lehmann, Regina']",Retrovirology,,,True
8a14b75626a9cad7cac350437b7af5e0e4bd5127,PMC,Bat origin of human coronaviruses,http://dx.doi.org/10.1186/s12985-015-0422-1,PMC4687304,26689940,CC BY,"Bats have been recognized as the natural reservoirs of a large variety of viruses. Special attention has been paid to bat coronaviruses as the two emerging coronaviruses which have caused unexpected human disease outbreaks in the 21st century, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), are suggested to be originated from bats. Various species of horseshoe bats in China have been found to harbor genetically diverse SARS-like coronaviruses. Some strains are highly similar to SARS-CoV even in the spike protein and are able to use the same receptor as SARS-CoV for cell entry. On the other hand, diverse coronaviruses phylogenetically related to MERS-CoV have been discovered worldwide in a wide range of bat species, some of which can be classified to the same coronavirus species as MERS-CoV. Coronaviruses genetically related to human coronavirus 229E and NL63 have been detected in bats as well. Moreover, intermediate hosts are believed to play an important role in the transmission and emergence of these coronaviruses from bats to humans. Understanding the bat origin of human coronaviruses is helpful for the prediction and prevention of another pandemic emergence in the future.",2015 Dec 22,"['Hu, Ben', 'Ge, Xingyi', 'Wang, Lin-Fa', 'Shi, Zhengli']",Virol J,,,True
f6fcf1a99cbd073c5821d1c4ffa3f2c6daf8ae29,PMC,"MERS coronavirus: diagnostics, epidemiology and transmission",http://dx.doi.org/10.1186/s12985-015-0439-5,PMC4687373,26695637,CC BY,"The first known cases of Middle East respiratory syndrome (MERS), associated with infection by a novel coronavirus (CoV), occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia (KSA). Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels (DC). MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract (LRT) disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute respiratory syndrome (SARS), another sometimes- fatal zoonotic coronavirus disease that has since disappeared, MERS progresses more rapidly to respiratory failure and acute kidney injury (it also has an affinity for growth in kidney cells under laboratory conditions), is more frequently reported in patients with underlying disease and is more often fatal. Most human cases of MERS have been linked to lapses in infection prevention and control (IPC) in healthcare settings, with approximately 20 % of all virus detections reported among healthcare workers (HCWs) and higher exposures in those with occupations that bring them into close contact with camels. Sero-surveys have found widespread evidence of past infection in adult camels and limited past exposure among humans. Sensitive, validated reverse transcriptase real-time polymerase chain reaction (RT-rtPCR)-based diagnostics have been available almost from the start of the emergence of MERS. While the basic virology of MERS-CoV has advanced over the past three years, understanding of the interplay between camel, environment, and human remains limited. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0439-5) contains supplementary material, which is available to authorized users.",2015 Dec 22,"['Mackay, Ian M.', 'Arden, Katherine E.']",Virol J,,,True
6fdb54d00b9abc340c37abe6fe840458a8eab54b,PMC,First case of Propionibacterium acnes urinary tract infection in a dog,http://dx.doi.org/10.1186/s12917-015-0620-5,PMC4687383,26690238,CC BY,"BACKGROUND: Propionibacterium acnes has been rarely isolated as a commensal from dogs, but there is little evidence of pathogenicity. Urinary tract infections are common in dogs and are typically caused by various commensal bacteria. Here we present the first case report of a urinary tract infection caused by P. acnes. CASE PRESENTATION: A 6-year-old female Japanese Shiba Inu was hospitalized for polyuria, polydipsia, and severe hematuria. At admission, blood tests revealed leukocytosis, slight anemia, decreased albumin, and slightly elevated blood urea nitrogen. Computerized tomography showed gas accumulation on the inner side of the bladder wall. Urinalysis revealed proteinuria and bilirubinuria without glycosuria. The urine sediment contained large numbers of erythrocytes and leukocytes. Additionally, rod-shaped bacteria were detected by Diff-Quik staining. Enrofloxacin and metronidazole were administered empirically; however, the renal function declined sharply and the patient died 2 days later. Bacteriological examination revealed that the causative agent was Propionibacterium acnes, which was identified as sequence type 53 via multilocus sequence typing. This isolate showed high susceptibility to ampicillin, amoxicillin/clavulanic acid, cefoxitin, imipenem, clindamycin, tetracycline, chloramphenicol, and enrofloxacin, but was resistant to metronidazole. CONCLUSION: To the best of our knowledge, this is the first case report of a dog with urinary tract infection caused by P. acnes.",2015 Dec 21,"['Harada, Kazuki', 'Shimizu, Takae', 'Tsuka, Takeshi', 'Imagawa, Tomohiro', 'Takeuchi, Takashi']",BMC Vet Res,,,True
60cfb43ca9b8d54f5b8cb4ab264d8d628c7c227b,PMC,Early occurrence of influenza A epidemics coincided with changes in occurrence of other respiratory virus infections,http://dx.doi.org/10.1111/irv.12348,PMC4687500,26369646,CC BY,"BACKGROUND: Viral interaction in which outbreaks of influenza and other common respiratory viruses might affect each other has been postulated by several short studies. Regarding longer time periods, influenza epidemics occasionally occur very early in the season, as during the 2009 pandemic. Whether early occurrence of influenza epidemics impacts outbreaks of other common seasonal viruses is not clear. OBJECTIVES: We investigated whether early occurrence of influenza outbreaks coincides with shifts in the occurrence of other common viruses, including both respiratory and non‐respiratory viruses. METHODS: We investigated time trends of and the correlation between positive laboratory diagnoses of eight common viruses in the Netherlands over a 10‐year time period (2003–2012): influenza viruses types A and B, respiratory syncytial virus (RSV), rhinovirus, coronavirus, norovirus, enterovirus, and rotavirus. We compared trends in viruses between early and late influenza seasons. RESULTS: Between 2003 and 2012, influenza B, RSV, and coronavirus showed shifts in their occurrence when influenza A epidemics occurred earlier than usual (before week 1). Although shifts were not always consistently of the same type, when influenza type A hit early, RSV outbreaks tended to be delayed, coronavirus outbreaks tended to be intensified, and influenza virus type B tended not to occur at all. Occurrence of rhinovirus, norovirus, rotavirus, and enterovirus did not change. CONCLUSION: When influenza A epidemics occured early, timing of the epidemics of several respiratory winter viruses usually occurring close in time to influenza A was affected, while trends in rhinoviruses (occurring in autumn) and trends in enteral viruses were not.",2016 Jan 11,"['van Asten, Liselotte', 'Bijkerk, Paul', 'Fanoy, Ewout', 'van Ginkel, Annemarijn', 'Suijkerbuijk, Anita', 'van der Hoek, Wim', 'Meijer, Adam', 'Vennema, Harry']",Influenza Other Respir Viruses,,,True
59d9705d1665532f12f9014317352297b8a834e3,PMC,Direct costs of acute respiratory infections in a pediatric long‐term care facility,http://dx.doi.org/10.1111/irv.12350,PMC4687501,26425787,CC BY,"Acute respiratory tract infections (ARI) are a major burden in pediatric long‐term care. We analyzed the financial impact of ARI in 2012–2013. Costs associated with ARI during the respiratory viral season were ten times greater than during the non‐respiratory viral season, $31 224 and $3242 per 1000 patient‐days, respectively (P < 0·001). ARI are burdensome for pediatric long‐term care facilities not only because of the associated morbidity and mortality, but also due to the great financial costs of prevention.",2016 Jan 11,"['Murray, Meghan T.', 'Heitkemper, Elizabeth', 'Jackson, Olivia', 'Neu, Natalie', 'Stone, Patricia', 'Cohen, Bevin', 'Saiman, Lisa', 'Hutcheon, Gordon', 'Larson, Elaine L.']",Influenza Other Respir Viruses,,,True
1efd8ee0124faf388961ff309a10ca2cfba5268c,PMC,Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study,http://dx.doi.org/10.1371/journal.pone.0145447,PMC4687909,26696249,CC BY,"BACKGROUND: There are very limited data on children with pneumonia in Mali. The objective was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children <5 years of age in Mali. METHODS: A prospective hospital-based case-control study was implemented in the Pediatric department of Gabriel Touré University Hospital at Bamako, Mali, between July 2011-December 2012. Cases were children with radiologically-confirmed pneumonia; Controls were hospitalized children without respiratory features, matched for age and period. Respiratory specimens, were collected to identify 19 viruses and 5 bacteria. Whole blood was collected from cases only. Factors associated with pneumonia were assessed by multivariate logistic regression. RESULTS: Overall, 118 cases and 98 controls were analyzed; 44.1% were female, median age was 11 months. Among pneumonia cases, 30.5% were hypoxemic at admission, mortality was 4.2%. Pneumonia cases differed from the controls regarding clinical signs and symptoms but not in terms of past medical history. Multivariate analysis of nasal swab findings disclosed that S. pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6–7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0–151.4), respiratory syncytial virus [RSV] (aOR = 7.4, 95% CI: 2.3–23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0–112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. Distribution of S. pneumoniae and RSV differed by season with higher rates of S. pneumoniae in January-June and of RSV in July-September. Pneumococcal serotypes 1 and 5 were more frequent in pneumonia cases than in the controls (P = 0.009, and P = 0.04, respectively). CONCLUSIONS: In this non-PCV population from Mali, pneumonia in children was mainly attributed to S. pneumoniae, RSV, human metapneumovirus, and influenza A virus. Increased pneumococcal conjugate vaccine coverage in children could significantly reduce the burden of pneumonia in sub-Saharan African countries.",2015 Dec 22,"['Bénet, Thomas', 'Sylla, Mariam', 'Messaoudi, Mélina', 'Sánchez Picot, Valentina', 'Telles, Jean-Noël', 'Diakite, Abdoul-Aziz', 'Komurian-Pradel, Florence', 'Endtz, Hubert', 'Diallo, Souleymane', 'Paranhos-Baccalà, Gláucia', 'Vanhems, Philippe']",PLoS One,,,True
db30c72b055266cbd06bb14d7f570f91d8e84e6e,PMC,Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus,http://dx.doi.org/10.1371/journal.pone.0145561,PMC4689477,26701103,CC BY,"The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4), the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection.",2015 Dec 23,"['Zhao, Guangyu', 'Jiang, Yuting', 'Qiu, Hongjie', 'Gao, Tongtong', 'Zeng, Yang', 'Guo, Yan', 'Yu, Hong', 'Li, Junfeng', 'Kou, Zhihua', 'Du, Lanying', 'Tan, Wenjie', 'Jiang, Shibo', 'Sun, Shihui', 'Zhou, Yusen']",PLoS One,,,True
473207b36a728a21e7545bcde584d8618f714552,PMC,2015 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) nosocomial outbreak in South Korea: insights from modeling,http://dx.doi.org/10.7717/peerj.1505,PMC4690341,26713252,CC BY,"Background. Since the emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012, more than 1,300 laboratory confirmed cases of MERS-CoV infections have been reported in Asia, North Africa, and Europe by July 2015. The recent MERS-CoV nosocomial outbreak in South Korea quickly became the second largest such outbreak with 186 total cases and 36 deaths in a little more than one month, second only to Saudi Arabia in country-specific number of reported cases. Methods. We use a simple mathematical model, the Richards model, to trace the temporal course of the South Korea MERS-CoV outbreak. We pinpoint its outbreak turning point and its transmissibility via basic reproduction number R(0) in order to ascertain the occurrence of this nosocomial outbreak and how it was quickly brought under control. Results. The estimated outbreak turning point of t(i) = 23.3 days (95% CI [22.6–24.0]), or 23–24 days after the onset date of the index case on May 11, pinpoints June 3–4 as the time of the turning point or the peak incidence for this outbreak by onset date. R(0) is estimated to range between 7.0 and 19.3. Discussion and Conclusion. The turning point of the South Korea MERS-CoV outbreak occurred around May 27–29, when control measures were quickly implemented after laboratory confirmation of the first cluster of nosocomial infections by the index patient. Furthermore, transmissibility of MERS-CoV in the South Korea outbreak was significantly higher than those reported from past MERS-CoV outbreaks in the Middle East, which is attributable to the nosocomial nature of this outbreak. Our estimate of R(0) for the South Korea MERS-CoV nosocomial outbreak further highlights the importance and the risk involved in cluster infections and superspreading events in crowded settings such as hospitals. Similar to the 2003 SARS epidemic, outbreaks of infectious diseases with low community transmissibility like MERS-CoV could still occur initially with large clusters of nosocomial infections, but can be quickly and effectively controlled with timely intervention measures.",2015 Dec 17,"Hsieh, Ying-Hen",PeerJ,,,True
b2d2050a4b62e13a5c78e23190f61a7895ca33e2,PMC,Analysis of synonymous codon usage patterns in sixty-four different bivalve species,http://dx.doi.org/10.7717/peerj.1520,PMC4690358,26713259,CC BY,"Synonymous codon usage bias (CUB) is a defined as the non-random usage of codons encoding the same amino acid across different genomes. This phenomenon is common to all organisms and the real weight of the many factors involved in its shaping still remains to be fully determined. So far, relatively little attention has been put in the analysis of CUB in bivalve mollusks due to the limited genomic data available. Taking advantage of the massive sequence data generated from next generation sequencing projects, we explored codon preferences in 64 different species pertaining to the six major evolutionary lineages in Bivalvia. We detected remarkable differences across species, which are only partially dependent on phylogeny. While the intensity of CUB is mild in most organisms, a heterogeneous group of species (including Arcida and Mytilida, among the others) display higher bias and a strong preference for AT-ending codons. We show that the relative strength and direction of mutational bias, selection for translational efficiency and for translational accuracy contribute to the establishment of synonymous codon usage in bivalves. Although many aspects underlying bivalve CUB still remain obscure, we provide for the first time an overview of this phenomenon in this large, commercially and environmentally important, class of marine invertebrates.",2015 Dec 14,"['Gerdol, Marco', 'De Moro, Gianluca', 'Venier, Paola', 'Pallavicini, Alberto']",PeerJ,,,True
1392d02729b5e2f1a63ff3ff259e10a8c45e5a55,PMC,The effectiveness of a shared conference experience in improving undergraduate medical and nursing students’ attitudes towards inter-professional education in an Asian country: a before and after study,http://dx.doi.org/10.1186/s12909-015-0509-9,PMC4690434,26698562,CC BY,"BACKGROUND: In recent years, increasing emphasis has been placed on the importance of collaboration within multi-disciplinary healthcare teams, so as to facilitate holistic patient care and thus allow improved treatment outcomes. There is hence an urgent need to educate healthcare undergraduates early in their professional careers on the importance of and complexities involved in cooperating with counterparts from other allied healthcare professions. In conjunction with this, a milestone student-led conference for undergraduate students, the 9th Student Medical-Nursing Education Conference (SMEC), was organised in 2013 to provide a unique opportunity for shared learning among the entire cohort of undergraduate medical and nursing students in Singapore matriculating in that year. METHODS: This study evaluated the effectiveness of the 9th SMEC 2013 as a shared conference experience in improving the attitudes of undergraduate medical and nursing students in Singapore towards inter-professional education (IPE). A 19-point Readiness for Inter-Professional Learning Scale (RIPLS) questionnaire comprising three subscales was administered to participants both before and after the conference. 352 responses were collected, giving a response rate of 75.1 %. Results were analysed using paired-samples t-tests with statistical significance set at p = 0.05. RESULTS: Improvements in overall scores for both medical and nursing students were reported for all three RIPLS subscales. Examining the RIPLS items individually, significant improvement in scores for both medical and nursing students was obtained in all 19 items. Prior exposure to IPE activities was not a predictor of improvement in IPE attitudes. CONCLUSION: The authors propose that student-led jointly-organised conference experiences are effective in improving healthcare students’ attitudes towards IPE. This study provides valuable insights to facilitate the development of further IPE programs to allow for the rapid and effective promotion of cooperation and collaboration between students across various healthcare disciplines.",2015 Dec 23,"['Chua, Amelia ZE', 'Lo, Daryl YK', 'Ho, Wilbert HH', 'Koh, Yun Qing', 'Lim, Daniel SY', 'Tam, John KC', 'Liaw, Sok Ying', 'Koh, Gerald CH']",BMC Med Educ,,,True
64c59c6ee1a8693c4bc296bf844047426f046e1b,PMC,Activation of the Mitochondrial Apoptotic Signaling Platform during Rubella Virus Infection,http://dx.doi.org/10.3390/v7122928,PMC4690853,26703711,CC BY,"Mitochondria- as well as p53-based signaling pathways are central for the execution of the intrinsic apoptotic cascade. Their contribution to rubella virus (RV)-induced apoptosis was addressed through time-specific evaluation of characteristic parameters such as permeabilization of the mitochondrial membrane and subsequent release of the pro-apoptotic proteins apoptosis-inducing factor (AIF) and cytochrome c from mitochondria. Additionally, expression and localization pattern of p53 and selected members of the multifunctional and stress-inducible cyclophilin family were examined. The application of pifithrin μ as an inhibitor of p53 shuttling to mitochondria reduced RV-induced cell death to an extent similar to that of the broad spectrum caspase inhibitor z-VAD-fmk (benzyloxycarbonyl-V-A-D-(OMe)-fmk). However, RV progeny generation was not altered. This indicates that, despite an increased survival rate of its cellular host, induction of apoptosis neither supports nor restricts RV replication. Moreover, some of the examined apoptotic markers were affected in a strain-specific manner and differed between the cell culture-adapted strains: Therien and the HPV77 vaccine on the one hand, and a clinical isolate on the other. In summary, the results presented indicate that the transcription-independent mitochondrial p53 program contributes to RV-induced apoptosis.",2015 Nov 26,"['Claus, Claudia', 'Manssen, Lena', 'Hübner, Denise', 'Roßmark, Sarah', 'Bothe, Viktoria', 'Petzold, Alice', 'Große, Claudia', 'Reins, Mareen', 'Mankertz, Annette', 'Frey, Teryl K.', 'Liebert, Uwe G.']",Viruses,,,True
d9d2f8f421d0290a8dbf0ec92cbbe1ad2d93a694,PMC,Alphacoronaviruses Detected in French Bats Are Phylogeographically Linked to Coronaviruses of European Bats,http://dx.doi.org/10.3390/v7122937,PMC4690861,26633467,CC BY,"Bats are a reservoir for a diverse range of viruses, including coronaviruses (CoVs). To determine the presence of CoVs in French bats, fecal samples were collected between July and August of 2014 from four bat species in seven different locations around the city of Bourges in France. We present for the first time the presence of alpha-CoVs in French Pipistrellus pipistrellus bat species with an estimated prevalence of 4.2%. Based on the analysis of a fragment of the RNA-dependent RNA polymerase (RdRp) gene, phylogenetic analyses show that alpha-CoVs sequences detected in French bats are closely related to other European bat alpha-CoVs. Phylogeographic analyses of RdRp sequences show that several CoVs strains circulate in European bats: (i) old strains detected that have probably diverged a long time ago and are detected in different bat subspecies; (ii) strains detected in Myotis and Pipistrellus bat species that have more recently diverged. Our findings support previous observations describing the complexity of the detected CoVs in bats worldwide.",2015 Dec 2,"['Goffard, Anne', 'Demanche, Christine', 'Arthur, Laurent', 'Pinçon, Claire', 'Michaux, Johan', 'Dubuisson, Jean']",Viruses,,,True
86effe356ffd602c096c4252ef1775dab6f62e1f,PMC,Viral Infection at High Magnification: 3D Electron Microscopy Methods to Analyze the Architecture of Infected Cells,http://dx.doi.org/10.3390/v7122940,PMC4690864,26633469,CC BY,"As obligate intracellular parasites, viruses need to hijack their cellular hosts and reprogram their machineries in order to replicate their genomes and produce new virions. For the direct visualization of the different steps of a viral life cycle (attachment, entry, replication, assembly and egress) electron microscopy (EM) methods are extremely helpful. While conventional EM has given important information about virus-host cell interactions, the development of three-dimensional EM (3D-EM) approaches provides unprecedented insights into how viruses remodel the intracellular architecture of the host cell. During the last years several 3D-EM methods have been developed. Here we will provide a description of the main approaches and examples of innovative applications.",2015 Dec 3,"['Romero-Brey, Inés', 'Bartenschlager, Ralf']",Viruses,,,True
6c9ce983d25f6c0727c9e4fedc01e84b046673a4,PMC,Molecular Epidemiology of Human Rhinoviruses and Enteroviruses Highlights Their Diversity in Sub-Saharan Africa,http://dx.doi.org/10.3390/v7122948,PMC4690871,26670243,CC BY,"Human rhinoviruses (HRVs) and enteroviruses (HEVs) belong to the Enterovirus genus and are the most frequent cause of infection worldwide, but data on their molecular epidemiology in Africa are scarce. To understand HRV and HEV molecular epidemiology in this setting, we enrolled febrile pediatric patients participating in a large prospective cohort assessing the causes of fever in Tanzanian children. Naso/oropharyngeal swabs were systematically collected and tested by real-time RT-PCR for HRV and HEV. Viruses from positive samples were sequenced and phylogenetic analyses were then applied to highlight the HRV and HEV types as well as recombinant or divergent strains. Thirty-eight percent (378/1005) of the enrolled children harboured an HRV or HEV infection. Although some types were predominant, many distinct types were co-circulating, including a vaccinal poliovirus, HEV-A71 and HEV-D68. Three HRV-A recombinants were identified: HRV-A36/HRV-A67, HRV-A12/HRV-A67 and HRV-A96/HRV-A61. Four divergent HRV strains were also identified: one HRV-B strain and three HRV-C strains. This is the first prospective study focused on HRV and HEV molecular epidemiology in sub-Saharan Africa. This systematic and thorough large screening with careful clinical data management confirms the wide genomic diversity of these viruses, brings new insights about their evolution and provides data about associated symptoms.",2015 Dec 8,"['L’Huillier, Arnaud G.', 'Kaiser, Laurent', 'Petty, Tom J.', 'Kilowoko, Mary', 'Kyungu, Esther', 'Hongoa, Philipina', 'Vieille, Gaël', 'Turin, Lara', 'Genton, Blaise', 'D’Acremont, Valérie', 'Tapparel, Caroline']",Viruses,,,True
37637426a103bf21e7fe97c97de5087707655923,PMC,Molecular Epidemiology of Human Rhinoviruses and Enteroviruses Highlights Their Diversity in Sub-Saharan Africa,http://dx.doi.org/10.3390/v7122948,PMC4690871,26670243,CC BY,"Human rhinoviruses (HRVs) and enteroviruses (HEVs) belong to the Enterovirus genus and are the most frequent cause of infection worldwide, but data on their molecular epidemiology in Africa are scarce. To understand HRV and HEV molecular epidemiology in this setting, we enrolled febrile pediatric patients participating in a large prospective cohort assessing the causes of fever in Tanzanian children. Naso/oropharyngeal swabs were systematically collected and tested by real-time RT-PCR for HRV and HEV. Viruses from positive samples were sequenced and phylogenetic analyses were then applied to highlight the HRV and HEV types as well as recombinant or divergent strains. Thirty-eight percent (378/1005) of the enrolled children harboured an HRV or HEV infection. Although some types were predominant, many distinct types were co-circulating, including a vaccinal poliovirus, HEV-A71 and HEV-D68. Three HRV-A recombinants were identified: HRV-A36/HRV-A67, HRV-A12/HRV-A67 and HRV-A96/HRV-A61. Four divergent HRV strains were also identified: one HRV-B strain and three HRV-C strains. This is the first prospective study focused on HRV and HEV molecular epidemiology in sub-Saharan Africa. This systematic and thorough large screening with careful clinical data management confirms the wide genomic diversity of these viruses, brings new insights about their evolution and provides data about associated symptoms.",2015 Dec 8,"['L’Huillier, Arnaud G.', 'Kaiser, Laurent', 'Petty, Tom J.', 'Kilowoko, Mary', 'Kyungu, Esther', 'Hongoa, Philipina', 'Vieille, Gaël', 'Turin, Lara', 'Genton, Blaise', 'D’Acremont, Valérie', 'Tapparel, Caroline']",Viruses,,,False
277e85da79677586ae01bb02ea6e410ebc97fd29,PMC,Recent Progress towards Novel EV71 Anti-Therapeutics and Vaccines,http://dx.doi.org/10.3390/v7122949,PMC4690872,26670245,CC BY,"Enterovirus 71 (EV71) is a group of viruses that belongs to the Picornaviridae family, which also includes viruses such as polioviruses. EV71, together with coxsackieviruses, is widely known for its association with Hand Foot Mouth Disease (HFMD), which generally affects children age five and below. Besides HFMD, EV71 can also trigger more severe and life-threatening neurological conditions such as encephalitis. Considering the lack of a vaccine and antiviral drug against EV71, together with the increasing spread of these viruses, the development of such drugs and vaccines becomes the top priority in protecting our younger generations. This article, hence, reviews some of the recent progress in the formulations of anti-therapeutics and vaccine generation for EV71, covering (i) inactivated vaccines; (ii) baculovirus-expressed vaccines against EV71; (iii) human intravenous immunoglobulin (IVIg) treatment; and (iv) the use of monoclonal antibody therapy as a prevention and treatment for EV71 infections.",2015 Dec 8,"['Ng, Qingyong', 'He, Fang', 'Kwang, Jimmy']",Viruses,,,True
dd2054667f5f1db92d4649fc420d0d86dc39dcd9,PMC,CDC42 Use in Viral Cell Entry Processes by RNA Viruses,http://dx.doi.org/10.3390/v7122955,PMC4690878,26690467,CC BY,"The cellular actin cytoskeleton presents a barrier that must be overcome by many viruses, and it has become increasingly apparent many viral species have developed a diverse repertoire of mechanisms to hijack cellular actin-regulating signalling pathways as part of their cell entry processes. The Rho family GTPase Cdc42 is appreciated as a key moderator of cellular actin dynamics, and the development of specific Cdc42-inhibiting agents has given us an unprecedented ability to investigate its individual role in signalling pathways. However, investigative use of said agents, and the subsequent characterisation of the role Cdc42 plays in viral entry processes has been lacking. Here, we describe the current literature on the role of Cdc42 in human immunodeficiency virus (HIV)-1 cell entry, which represents the most investigated instance of Cdc42 function in viral cell entry processes, and also review evidence of Cdc42 use in other RNA virus cell entries, demonstrating prime areas for more extensive research using similar techniques.",2015 Dec 10,"['Swaine, Thomas', 'Dittmar, Matthias T.']",Viruses,,,True
e9011bcb647874593aa8c4c7a3010573f82a1558,PMC,Herpesvirus gB: A Finely Tuned Fusion Machine,http://dx.doi.org/10.3390/v7122957,PMC4690880,26690469,CC BY,"Enveloped viruses employ a class of proteins known as fusogens to orchestrate the merger of their surrounding envelope and a target cell membrane. Most fusogens accomplish this task alone, by binding cellular receptors and subsequently catalyzing the membrane fusion process. Surprisingly, in herpesviruses, these functions are distributed among multiple proteins: the conserved fusogen gB, the conserved gH/gL heterodimer of poorly defined function, and various non-conserved receptor-binding proteins. We summarize what is currently known about gB from two closely related herpesviruses, HSV-1 and HSV-2, with emphasis on the structure of the largely uncharted membrane interacting regions of this fusogen. We propose that the unusual mechanism of herpesvirus fusion could be linked to the unique architecture of gB.",2015 Dec 11,"['Cooper, Rebecca S.', 'Heldwein, Ekaterina E.']",Viruses,,,True
ed526e1eb5a7607af2803906e2f6d4e5bb2dff09,PMC,Potential Broad Spectrum Inhibitors of the Coronavirus 3CL(pro): A Virtual Screening and Structure-Based Drug Design Study,http://dx.doi.org/10.3390/v7122963,PMC4690886,26694449,CC BY,"Human coronaviruses represent a significant disease burden; however, there is currently no antiviral strategy to combat infection. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) less than 10 years later demonstrates the potential of coronaviruses to cross species boundaries and further highlights the importance of identifying novel lead compounds with broad spectrum activity. The coronavirus 3CL(pro) provides a highly validated drug target and as there is a high degree of sequence homology and conservation in main chain architecture the design of broad spectrum inhibitors is viable. The ZINC drugs-now library was screened in a consensus high-throughput pharmacophore modeling and molecular docking approach by Vina, Glide, GOLD and MM-GBSA. Molecular dynamics further confirmed results obtained from structure-based techniques. A highly defined hit-list of 19 compounds was identified by the structure-based drug design methodologies. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds is bioactive is excellent. Additionally, the compounds segregate into 15 significantly dissimilar (p < 0.05) clusters based on shape and features, which represent valuable scaffolds that can be used as a basis for future anti-coronaviral inhibitor discovery experiments. Importantly though, the enriched subset of 19 compounds identified from the larger library has to be validated experimentally.",2015 Dec 15,"['Berry, Michael', 'Fielding, Burtram C.', 'Gamieldien, Junaid']",Viruses,,,True
e2b5298da8d9d86daf286304637a644139dc6dc1,PMC,Glucose-6-Phosphate Dehydrogenase Enhances Antiviral Response through Downregulation of NADPH Sensor HSCARG and Upregulation of NF-κB Signaling,http://dx.doi.org/10.3390/v7122966,PMC4690889,26694452,CC BY,"Glucose-6-phosphate dehydrogenase (G6PD)-deficient cells are highly susceptible to viral infection. This study examined the mechanism underlying this phenomenon by measuring the expression of antiviral genes—tumor necrosis factor alpha (TNF-α) and GTPase myxovirus resistance 1 (MX1)—in G6PD-knockdown cells upon human coronavirus 229E (HCoV-229E) and enterovirus 71 (EV71) infection. Molecular analysis revealed that the promoter activities of TNF-α and MX1 were downregulated in G6PD-knockdown cells, and that the IκB degradation and DNA binding activity of NF-κB were decreased. The HSCARG protein, a nicotinamide adenine dinucleotide phosphate (NADPH) sensor and negative regulator of NF-κB, was upregulated in G6PD-knockdown cells with decreased NADPH/NADP(+) ratio. Treatment of G6PD-knockdown cells with siRNA against HSCARG enhanced the DNA binding activity of NF-κB and the expression of TNF-α and MX1, but suppressed the expression of viral genes; however, the overexpression of HSCARG inhibited the antiviral response. Exogenous G6PD or IDH1 expression inhibited the expression of HSCARG, resulting in increased expression of TNF-α and MX1 and reduced viral gene expression upon virus infection. Our findings suggest that the increased susceptibility of the G6PD-knockdown cells to viral infection was due to impaired NF-κB signaling and antiviral response mediated by HSCARG.",2015 Dec 17,"['Wu, Yi-Hsuan', 'Chiu, Daniel Tsun-Yee', 'Lin, Hsin-Ru', 'Tang, Hsiang-Yu', 'Cheng, Mei-Ling', 'Ho, Hung-Yao']",Viruses,,,True
91e6020c65dd5a92c89040f9e209d65e26ef2b7f,PMC,Therapeutic Targets for Neurodevelopmental Disorders Emerging from Animal Models with Perinatal Immune Activation,http://dx.doi.org/10.3390/ijms161226092,PMC4691039,26633355,CC BY,"Increasing epidemiological evidence indicates that perinatal infection with various viral pathogens enhances the risk for several psychiatric disorders. The pathophysiological significance of astrocyte interactions with neurons and/or gut microbiomes has been reported in neurodevelopmental disorders triggered by pre- and postnatal immune insults. Recent studies with the maternal immune activation or neonatal polyriboinosinic polyribocytidylic acid models of neurodevelopmental disorders have identified various candidate molecules that could be responsible for brain dysfunction. Here, we review the functions of several candidate molecules in neurodevelopment and brain function and discuss their potential as therapeutic targets for psychiatric disorders.",2015 Nov 27,"['Ibi, Daisuke', 'Yamada, Kiyofumi']",Int J Mol Sci,,,True
17cff89c1672094997155613467334c9b1b410e8,PMC,Plants as Factories for Human Pharmaceuticals: Applications and Challenges,http://dx.doi.org/10.3390/ijms161226122,PMC4691069,26633378,CC BY,"Plant molecular farming (PMF), defined as the practice of using plants to produce human therapeutic proteins, has received worldwide interest. PMF has grown and advanced considerably over the past two decades. A number of therapeutic proteins have been produced in plants, some of which have been through pre-clinical or clinical trials and are close to commercialization. Plants have the potential to mass-produce pharmaceutical products with less cost than traditional methods. Tobacco-derived antibodies have been tested and used to combat the Ebola outbreak in Africa. Genetically engineered immunoadhesin (DPP4-Fc) produced in green plants has been shown to be able to bind to MERS-CoV (Middle East Respiratory Syndrome), preventing the virus from infecting lung cells. Biosafety concerns (such as pollen contamination and immunogenicity of plant-specific glycans) and costly downstream extraction and purification requirements, however, have hampered PMF production from moving from the laboratory to industrial application. In this review, the challenges and opportunities of PMF are discussed. Topics addressed include; transformation and expression systems, plant bioreactors, safety concerns, and various opportunities to produce topical applications and health supplements.",2015 Dec 2,"['Yao, Jian', 'Weng, Yunqi', 'Dickey, Alexia', 'Wang, Kevin Yueju']",Int J Mol Sci,,,True
a263f1ec26e982b0f070dcb721f6e51e7d970889,PMC,A Porcine Epidemic Diarrhea Virus Outbreak in One Geographic Region of the United States: Descriptive Epidemiology and Investigation of the Possibility of Airborne Virus Spread,http://dx.doi.org/10.1371/journal.pone.0144818,PMC4692406,26709512,CC0,"This study describes a spring 2013 outbreak of porcine epidemic diarrhea virus (PEDv), using data from 222 swine sites in 14 counties area in 4 contiguous states in the United States. During the outbreak, the premises-level incidence of PEDv was 40.5 percent (90/222 sites). One of the three companies from which data were collected had a lower incidence (19.5 percent) than the other two companies (41.1 and 47.2 percent). Sow sites had the highest incidence of PEDv during the outbreak (80.0 percent). Spatial analysis showed that PEDv was clustered rather than randomly distributed, which suggested that sites near a positive site had increased risk of acquiring PEDv infection. Meteorological data were used to investigate the hypothesis that PEDv was spread by air. If airborne dissemination played a role in this outbreak, we would expect the direction of disease spread to correlate with the predominant wind direction. Two methods were used to determine the direction of disease spread—linear direction mean analysis in ArcGIS and the direction test in ClusterSeer. The former method indicated PEDv spread was south to slightly southwest, and the latter indicated spread was to the southeast. The predominant wind direction during the month of the outbreak was toward the south, with some southeast and southwest winds; the strongest wind gusts were toward the southwest. These findings support the hypothesis that PEDv was spread by air. The results, however, should be interpreted cautiously because we did not have information on direct and indirect contacts between sites, such as movement of trucks, feed, pigs or people. These types of contacts should be evaluated before pathogen spread is attributed to airborne mechanisms. Although this study did not provide a definitive assessment of airborne spread of PEDv, we believe the findings justify additional research to investigate this potential mechanism of transmission.",2015 Dec 28,"['Beam, Andrea', 'Goede, Dane', 'Fox, Andrew', 'McCool, Mary Jane', 'Wall, Goldlin', 'Haley, Charles', 'Morrison, Robert']",PLoS One,,,True
4c6efd303141e36db6479eda5dc5d2a379e6bcd9,PMC,Evolutionary Insights into IL17A in Lagomorphs,http://dx.doi.org/10.1155/2015/367670,PMC4692990,26788019,CC BY,"In leporids, IL17A had been implicated in the host defense against extracellular pathogens, such as Francisella tularensis that infects hares and rabbits and causes the zoonotic disease tularemia. Here, we studied IL17A from five lagomorphs, European rabbit, pygmy rabbit, brush rabbit, European brown hare, and American pika. We observed that this protein is highly conserved between these species, with a similarity of 97–99% in leporids and ~88% between leporids and American pika. The exon/intron structure, N-glycosylation sites, and cysteine residues are conserved between lagomorphs. However, at codon 88, one of the interaction sites between IL17A and its receptor IL17RA, there is an Arg>Pro mutation that only occurs in European rabbit and European brown hare. This could induce critical alterations in the IL17A structure and conformation and consequently modify its function. The differences observed between leporids and humans or rodents might also represent important alterations in protein structure and function. In addition, as for other interleukins, IL17A sequences of human and European rabbit are more closely related than the sequences of human and mouse or European rabbit and mouse. This study gives further support to the hypothesis that European rabbit might be a more suitable animal model for studies on human IL17.",2015 Dec 15,"['Neves, Fabiana', 'Abrantes, Joana', 'Almeida, Tereza', 'Costa, Paulo P.', 'Esteves, Pedro J.']",Mediators Inflamm,,,True
ba56c984234f222a42689dc2830c757add96b345,PMC,Full Genomic Characterization of a Saffold Virus Isolated in Peru,http://dx.doi.org/10.3390/pathogens4040816,PMC4693166,26610576,CC BY,While studying respiratory infections of unknown etiology we detected Saffold virus in an oropharyngeal swab collected from a two-year-old female suffering from diarrhea and respiratory illness. The full viral genome recovered by deep sequencing showed 98% identity to a previously described Saffold strain isolated in Japan. Phylogenetic analysis confirmed the Peruvian Saffold strain belongs to genotype 3 and is most closely related to strains that have circulated in Asia. This is the first documented case report of Saffold virus in Peru and the only complete genomic characterization of a Saffold-3 isolate from the Americas.,2015 Nov 20,"['Leguia, Mariana', 'Loyola, Steev', 'Rios, Jane', 'Juarez, Diana', 'Guevara, Carolina', 'Silva, Maria', 'Prieto, Karla', 'Wiley, Michael', 'Kasper, Matthew R.', 'Palacios, Gustavo', 'Bausch, Daniel G.']",Pathogens,,,True
bd2a3e44148e47e73516efdce7a8692b0f93fc3c,PMC,Full Genomic Characterization of a Saffold Virus Isolated in Peru,http://dx.doi.org/10.3390/pathogens4040816,PMC4693166,26610576,CC BY,While studying respiratory infections of unknown etiology we detected Saffold virus in an oropharyngeal swab collected from a two-year-old female suffering from diarrhea and respiratory illness. The full viral genome recovered by deep sequencing showed 98% identity to a previously described Saffold strain isolated in Japan. Phylogenetic analysis confirmed the Peruvian Saffold strain belongs to genotype 3 and is most closely related to strains that have circulated in Asia. This is the first documented case report of Saffold virus in Peru and the only complete genomic characterization of a Saffold-3 isolate from the Americas.,2015 Nov 20,"['Leguia, Mariana', 'Loyola, Steev', 'Rios, Jane', 'Juarez, Diana', 'Guevara, Carolina', 'Silva, Maria', 'Prieto, Karla', 'Wiley, Michael', 'Kasper, Matthew R.', 'Palacios, Gustavo', 'Bausch, Daniel G.']",Pathogens,,,False
8bae8e6308d50b3a053a98be3b0fd641c775c1ca,PMC,Two novel regulators of N‐acetyl‐galactosamine utilization pathway and distinct roles in bacterial infections,http://dx.doi.org/10.1002/mbo3.307,PMC4694137,26540018,CC BY,"Bacterial pathogens can exploit metabolic pathways to facilitate their successful infection cycles, but little is known about roles of d‐galactosamine (GalN)/N‐acetyl‐d‐galactosamine (GalNAc) catabolism pathway in bacterial pathogenesis. Here, we report the genomic reconstruction of GalN/GalNAc utilization pathway in Streptococci and the diversified aga regulons. We delineated two new paralogous AgaR regulators for the GalN/GalNAc catabolism pathway. The electrophoretic mobility shift assays experiment demonstrated that AgaR2 (AgaR1) binds the predicted palindromes, and the combined in vivo data from reverse transcription quantitative polymerase chain reaction and RNA‐seq suggested that AgaR2 (not AgaR1) can effectively repress the transcription of the target genes. Removal of agaR2 (not agaR1) from Streptococcus suis 05ZYH33 augments significantly the abilities of both adherence to Hep‐2 cells and anti‐phagocytosis against RAW264.7 macrophage. As anticipated, the dysfunction in AgaR2‐mediated regulation of S. suis impairs its pathogenicity in experimental models of both mice and piglets. Our finding discovered two novel regulators specific for GalN/GalNAc catabolism and assigned them distinct roles into bacterial infections. To the best of our knowledge, it might represent a first paradigm that links the GalN/GalNAc catabolism pathway to bacterial pathogenesis.",2015 Nov 5,"['Zhang, Huimin', 'Ravcheev, Dmitry A.', 'Hu, Dan', 'Zhang, Fengyu', 'Gong, Xiufang', 'Hao, Lina', 'Cao, Min', 'Rodionov, Dmitry A.', 'Wang, Changjun', 'Feng, Youjun']",Microbiologyopen,,,True
26e8ef0fab0bc606adadae018a73d8490c8e1cd5,PMC,Knock out of the BASIGIN/CD147 chaperone of lactate/H+ symporters disproves its pro-tumour action via extracellular matrix metalloproteases (MMPs) induction,,PMC4694784,26284589,CC BY,"BASIGIN/CD147/EMMPRIN is a multifunctional transmembrane glycoprotein strongly expressed in tumours. BASIGIN controls tumour metabolism, particularly glycolysis by facilitating lactic acid export through the two monocarboxylate transporters MCT1 and hypoxia-inducible MCT4. However, before being recognized as a co-carrier of MCTs, BASIGIN was described as an inducer of extracellular matrix metalloproteases (MMPs). Early on, a model emerged in which, tumour cells use the extracellular domain of BASIGIN to recognize and stimulate neighbouring fibroblasts to produce MMPs. However, this model has remained hypothetical since a direct link between BASIGIN and MMPs production has not yet been clearly established. To validate the BASIGIN/MMP hypothesis, we developed BASIGIN knockouts in three human tumour cell lines derived from glioma, colon, and lung adenocarcinoma. By using co-culture experiments of either human or mouse fibroblasts and tumour cell lines we showed, contrary to what has been abundantly published, that the disruption of BASIGIN in tumour cells and in MEFs has no action on the production of MMPs. Our findings do not support the notion that the pro-tumoural action of BASIGIN is mediated via induction of MMPs. Therefore, we propose that to date, the strongest pro-tumoural action of BASIGIN is mediated through the control of fermentative glycolysis.",2015 May 29,"['Marchiq, Ibtissam', 'Albrengues, Jean', 'Granja, Sara', 'Gaggioli, Cédric', 'Pouysségur, Jacques', 'Simon, Marie-Pierre']",Oncotarget,,,True
77c8f24d21f25774e383052c028b90b178c7b3d8,PMC,Intracellular Mono-ADP-Ribosylation in Signaling and Disease,http://dx.doi.org/10.3390/cells4040569,PMC4695847,26426055,CC BY,"A key process in the regulation of protein activities and thus cellular signaling pathways is the modification of proteins by post-translational mechanisms. Knowledge about the enzymes (writers and erasers) that attach and remove post-translational modifications, the targets that are modified and the functional consequences elicited by specific modifications, is crucial for understanding cell biological processes. Moreover detailed knowledge about these mechanisms and pathways helps to elucidate the molecular causes of various diseases and in defining potential targets for therapeutic approaches. Intracellular adenosine diphosphate (ADP)-ribosylation refers to the nicotinamide adenine dinucleotide (NAD(+))-dependent modification of proteins with ADP-ribose and is catalyzed by enzymes of the ARTD (ADP-ribosyltransferase diphtheria toxin like, also known as PARP) family as well as some members of the Sirtuin family. Poly-ADP-ribosylation is relatively well understood with inhibitors being used as anti-cancer agents. However, the majority of ARTD enzymes and the ADP-ribosylating Sirtuins are restricted to catalyzing mono-ADP-ribosylation. Although writers, readers and erasers of intracellular mono-ADP-ribosylation have been identified only recently, it is becoming more and more evident that this reversible post-translational modification is capable of modulating key intracellular processes and signaling pathways. These include signal transduction mechanisms, stress pathways associated with the endoplasmic reticulum and stress granules, and chromatin-associated processes such as transcription and DNA repair. We hypothesize that mono-ADP-ribosylation controls, through these different pathways, the development of cancer and infectious diseases.",2015 Sep 25,"['Bütepage, Mareike', 'Eckei, Laura', 'Verheugd, Patricia', 'Lüscher, Bernhard']",Cells,,,True
0c58e0eb436a3d0cb4c5acfa41babc03b3dfe825,PMC,"Implementing a One Health approach to emerging infectious disease: reflections on the socio-political, ethical and legal dimensions",http://dx.doi.org/10.1186/s12889-015-2617-1,PMC4696140,26715066,CC BY,"BACKGROUND: ‘One Health’ represents a call for health researchers and practitioners at the human, animal and environmental interfaces to work together to mitigate the risks of emerging and re-emerging infectious diseases (EIDs). A One Health approach emphasizing inter-disciplinary co-operation is increasingly seen as necessary for effective EID control and prevention. There are, however, socio-political, ethical and legal challenges, which must be met by such a One Health approach. DISCUSSION: Based on the philosophical review and critical analysis of scholarship around the theory and practice of One Health it is clear that EID events are not simply about pathogens jumping species barriers; they are comprised of complex and contingent sets of relations that involve socioeconomic and socio-political drivers and consequences with the latter extending beyond the impact of the disease. Therefore, the effectiveness of policies based on One Health depends on their implementation and alignment with or modification of public values. SUMMARY: Despite its strong motivating rationale, implementing a One Health approach in an integrated and considered manner can be challenging, especially in the face of a perceived crisis. The effective control and prevention of EIDs therefore requires: (i) social science research to improve understanding of how EID threats and responses play out; (ii) the development of an analytic framework that catalogues case experiences with EIDs, reflects their dynamic nature and promotes inter-sectoral collaboration and knowledge synthesis; (iii) genuine public engagement processes that promote transparency, education and capture people’s preferences; (iv) a set of practical principles and values that integrate ethics into decision-making procedures, against which policies and public health responses can be assessed; (v) integration of the analytic framework and the statement of principles and values outlined above; and (vi) a focus on genuine reform rather than rhetoric.",2015 Dec 29,"['Degeling, Chris', 'Johnson, Jane', 'Kerridge, Ian', 'Wilson, Andrew', 'Ward, Michael', 'Stewart, Cameron', 'Gilbert, Gwendolyn']",BMC Public Health,,,True
30d6338f9b3366f9d76e5cc76e6a79a4aa3f8c13,PMC,"First detection, clinical presentation and phylogenetic characterization of Porcine epidemic diarrhea virus in Austria",http://dx.doi.org/10.1186/s12917-015-0624-1,PMC4696200,26714453,CC BY,"BACKGROUND: Porcine epidemic diarrhea (PED) is a syndrome that is characterized by rapidly spreading watery diarrhea affecting pigs of all ages, but with major effects on suckling piglets. The disease, as well as the causative Alphacoronavirus, the Porcine epidemic diarrhea virus (PEDV), was first described in Europe in the 1970s and since then has spread over many Asian and American countries, where it recently led to devastating effects on swine health and pork industry. While the disease was seldom reported in Europe within the last few decades, a few recent reports re-emergence of PED in German pig farms. The hitherto isolated German strain seems to be closely related to a low pathogenic PEDV variant from the USA. This case report describes the first detection of PEDV in Austria. CASE PRESENTATION: Reduced feed uptake and occasional diarrhea were observed in December 2014 in a group of fattening pigs, kept on an Austrian swine farm. The concerned pigs had been recently purchased from Germany. Within a few weeks, diarrhea became apparent also in pigs of Austrian origin, which were kept in a different stable on the same farm. Gastrointestinal symptoms among fattening pigs were generally mild, quickly resolving and did not lead to death. PEDV RNA was identified by RT-qPCR in pooled feces and serum and PEDV antibodies were detectable in serum in both groups of pigs. Phylogenetic analysis of the nearly complete PEDV spike gene shows that the Austrian PEDV strain is highly similar to other strains involved in recent outbreaks in Western and Central Europe. CONCLUSION: This is the first report demonstrating the presence of PEDV in Austria. The virus was probably introduced by purchasing piglets from a German source, which underlines the significance of trans-boundary animal trade for the distribution of highly contagious diseases, such as PED. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0624-1) contains supplementary material, which is available to authorized users.",2015 Dec 30,"['Steinrigl, Adolf', 'Revilla Fernández, Sandra', 'Stoiber, Friedrich', 'Pikalo, Jutta', 'Sattler, Tatjana', 'Schmoll, Friedrich']",BMC Vet Res,,,True
ec955d5ff9dc3bdb037e561ee890c4c18fdb4272,PMC,Phylogenetic investigation of enteric bovine coronavirus in Ireland reveals partitioning between European and global strains,http://dx.doi.org/10.1186/s13620-015-0060-3,PMC4696222,26719792,CC BY,"BACKGROUND: Bovine coronavirus is a primary cause of neonatal calf diarrhea worldwide, and is also associated with acute diarrhea in adult cattle during the winter season. There are no reports on molecular characterization of bovine coronavirus in Ireland, and little data exists apart from serological studies. FINDINGS: In this study, 11 neonatal (mean age 9 days) calf BCoV strains from the south of Ireland were collected over a one year period and characterized using molecular methods. The spike gene which encodes a protein involved in viral entry, infectivity and immune response shows the most variability amongst the isolates and was subsequently selected for in depth analysis. Phylogenetic analysis of the spike gene revealed that the Irish strains clustered with novel BCoV strains from Europe in a unique clade, possibly indicating lineage partitioning. Direct analysis of alignments identified amino acid changes in the spike protein unique to the Irish clade. CONCLUSION: Thus, monitoring of bovine coronavirus in Ireland is important as the current isolates in circulation in the south of Ireland may be diverging from the available vaccine strain, which may have implications regarding future BCoV vaccine efficacy.",2015 Dec 30,"['Gunn, L.', 'Collins, P. J.', 'O’Connell, M. J.', 'O’Shea, H.']",Ir Vet J,,,True
272c6cc36e652db7f8d263194c13b2a5c92ed92e,PMC,"Pathosphere.org: pathogen detection and characterization through a web-based, open source informatics platform",http://dx.doi.org/10.1186/s12859-015-0840-5,PMC4696252,26714571,CC BY,"BACKGROUND: The detection of pathogens in complex sample backgrounds has been revolutionized by wide access to next-generation sequencing (NGS) platforms. However, analytical methods to support NGS platforms are not as uniformly available. Pathosphere (found at Pathosphere.org) is a cloud - based open - sourced community tool that allows for communication, collaboration and sharing of NGS analytical tools and data amongst scientists working in academia, industry and government. The architecture allows for users to upload data and run available bioinformatics pipelines without the need for onsite processing hardware or technical support. RESULTS: The pathogen detection capabilities hosted on Pathosphere were tested by analyzing pathogen-containing samples sequenced by NGS with both spiked human samples as well as human and zoonotic host backgrounds. Pathosphere analytical pipelines developed by Edgewood Chemical Biological Center (ECBC) identified spiked pathogens within a common sample analyzed by 454, Ion Torrent, and Illumina sequencing platforms. ECBC pipelines also correctly identified pathogens in human samples containing arenavirus in addition to animal samples containing flavivirus and coronavirus. These analytical methods were limited in the detection of sequences with limited homology to previous annotations within NCBI databases, such as parvovirus. Utilizing the pipeline-hosting adaptability of Pathosphere, the analytical suite was supplemented by analytical pipelines designed by the United States Army Medical Research Insititute of Infectious Diseases and Walter Reed Army Institute of Research (USAMRIID-WRAIR). These pipelines were implemented and detected parvovirus sequence in the sample that the ECBC iterative analysis previously failed to identify. CONCLUSIONS: By accurately detecting pathogens in a variety of samples, this work demonstrates the utility of Pathosphere and provides a platform for utilizing, modifying and creating pipelines for a variety of NGS technologies developed to detect pathogens in complex sample backgrounds. These results serve as an exhibition for the existing pipelines and web-based interface of Pathosphere as well as the plug-in adaptability that allows for integration of newer NGS analytical software as it becomes available. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0840-5) contains supplementary material, which is available to authorized users.",2015 Dec 29,"['Kilianski, Andy', 'Carcel, Patrick', 'Yao, Shijie', 'Roth, Pierce', 'Schulte, Josh', 'Donarum, Greg B.', 'Fochler, Ed T.', 'Hill, Jessica M.', 'Liem, Alvin T.', 'Wiley, Michael R.', 'Ladner, Jason T.', 'Pfeffer, Bradley P.', 'Elliot, Oliver', 'Petrosov, Alexandra', 'Jima, Dereje D.', 'Vallard, Tyghe G.', 'Melendrez, Melanie C.', 'Skowronski, Evan', 'Quan, Phenix-Lan', 'Lipkin, W. Ian', 'Gibbons, Henry S.', 'Hirschberg, David L.', 'Palacios, Gustavo F.', 'Rosenzweig, C. Nicole']",BMC Bioinformatics,,,True
5819ca9f401da096d402b6d1956a4fe6ba1c74b0,PMC,A simple novel device for air sampling by electrokinetic capture,http://dx.doi.org/10.1186/s40168-015-0141-2,PMC4696304,26715467,CC BY,"BACKGROUND: A variety of different sampling devices are currently available to acquire air samples for the study of the microbiome of the air. All have a degree of technical complexity that limits deployment. Here, we evaluate the use of a novel device, which has no technical complexity and is easily deployable. RESULTS: An air-cleaning device powered by electrokinetic propulsion has been adapted to provide a universal method for collecting samples of the aerobiome. Plasma-induced charge in aerosol particles causes propulsion to and capture on a counter-electrode. The flow of ions creates net bulk airflow, with no moving parts. A device and electrode assembly have been re-designed from air-cleaning technology to provide an average air flow of 120 lpm. This compares favorably with current air sampling devices based on physical air pumping. Capture efficiency was determined by comparison with a 0.4 μm polycarbonate reference filter, using fluorescent latex particles in a controlled environment chamber. Performance was compared with the same reference filter method in field studies in three different environments. For 23 common fungal species by quantitative polymerase chain reaction (qPCR), there was 100 % sensitivity and apparent specificity of 87 %, with the reference filter taken as “gold standard.” Further, bacterial analysis of 16S RNA by amplicon sequencing showed equivalent community structure captured by the electrokinetic device and the reference filter. Unlike other current air sampling methods, capture of particles is determined by charge and so is not controlled by particle mass. We analyzed particle sizes captured from air, without regard to specific analyte by atomic force microscopy: particles at least as low as 100 nM could be captured from ambient air. CONCLUSIONS: This work introduces a very simple plug-and-play device that can sample air at a high-volume flow rate with no moving parts and collect particles down to the sub-micron range. The performance of the device is substantially equivalent to capture by pumping through a filter for microbiome analysis by quantitative PCR and amplicon sequencing.",2015 Dec 27,"['Gordon, Julian', 'Gandhi, Prasanthi', 'Shekhawat, Gajendra', 'Frazier, Angel', 'Hampton-Marcell, Jarrad', 'Gilbert, Jack A.']",Microbiome,,,True
8de35b5317b0ebc437a5d5dbe94100f93ff88ab1,PMC,Moving pathogen genomics out of the lab and into the clinic: what will it take?,http://dx.doi.org/10.1186/s13073-015-0254-z,PMC4697326,26719100,CC BY,"Pathogen genomic analysis is a potentially transformative new approach to the clinical and public-health management of infectious diseases. Health systems investing in this technology will need to build infrastructure and develop policies that ensure genomic information can be generated, shared and acted upon in a timely manner.",2015 Dec 30,"['Luheshi, Leila M.', 'Raza, Sobia', 'Peacock, Sharon J.']",Genome Med,,,True
97bdba1d4a122241576c1e180ca7ce848cb657a3,PMC,Evaluation of humoral immune status in porcine epidemic diarrhea virus (PEDV) infected sows under field conditions,http://dx.doi.org/10.1186/s13567-015-0285-x,PMC4699368,26667229,CC BY,"Porcine epidemic diarrhea virus (PEDV) is an economically devastating enteric disease in the swine industry. The virus infects pigs of all ages, but it cause severe clinical disease in neonatal suckling pigs with up to 100% mortality. Currently, available vaccines are not completely effective and feedback methods utilizing PEDV infected material has variable success in preventing reinfection. Comprehensive information on the levels and duration of effector/memory IgA and IgG antibody secreting B cell response in the intestines and lymphoid organs of PEDV-infected sows, and their association with specific antibody levels in clinical samples such as plasma, oral fluid, and feces is important. Therefore, our goal in this study was to quantify PEDV specific IgA and IgG B cell responses in sows at approximately 1 and 6 months post-infection in commercial swine herds, including parity one and higher sows. Our data indicated that evaluation of both PEDV specific IgA and IgG antibody levels in the plasma and oral fluid (but not feces) samples is beneficial in disease diagnosis. PEDV specific B cell response in the intestine and spleen of infected sows decline by 6 months, and this associates with specific antibody levels in the plasma and oral fluid samples; but the virus neutralization titers in plasma remains high beyond 6 months post-infection. In conclusion, in sows infected with PEDV the presence of effector/memory B cell response and strong virus neutralization titers in plasma up to 6 months post-infection, suggests their potential to protect sows from reinfection and provide maternal immunity to neonates, but challenge studies are required to confirm such responses.",2015 Dec 14,"['Ouyang, Kang', 'Shyu, Duan-Liang', 'Dhakal, Santosh', 'Hiremath, Jagadish', 'Binjawadagi, Basavaraj', 'Lakshmanappa, Yashavanth S.', 'Guo, Rui', 'Ransburgh, Russell', 'Bondra, Kathryn M.', 'Gauger, Phillip', 'Zhang, Jianqiang', 'Specht, Terry', 'Gilbertie, Aaron', 'Minton, William', 'Fang, Ying', 'Renukaradhya, Gourapura J.']",Vet Res,,,True
37e2ecefeffdf8d95f1509809b59fe0464abba44,PMC,"Prostaglandin E(2) stimulates normal bronchial epithelial cell growth through induction of c-Jun and PDK1, a kinase implicated in oncogenesis",http://dx.doi.org/10.1186/s12931-015-0309-0,PMC4699375,26684827,CC BY,"BACKGROUND: Cyclooxygenase-2-derived prostaglandin E(2) (PGE(2)), a bioactive eicosanoid, has been implicated in many biological processes including reproduction, inflammation and tumor growth. We previously showed that PGE(2) stimulated lung cancer cell growth and progression through PGE(2) receptor EP2/EP4-mediated kinase signaling pathways. However, the role of PGE(2) in controlling lung airway epithelial cell phenotype remains unknown. We evaluated the effects of c-Jun and 3-phosphoinositede dependent protein kinase-1 (PDK1) in mediating epithelial cell hyperplasia induced by PGE(2). METHOD: The bronchial epithelial cell lines BEAS-2B and HBEc14-KT were cultured and then treated with PGE(2). PDK1 small interfering RNA (siRNA) and a PDK1 inhibitor, an antagonist of the PGE(2) receptor subtype EP4 and EP4 siRNA, c-Jun siRNA, and overexpressions of c-Jun and PDK1 have been used to evaluate the effects on cell proliferation. RESULTS: We demonstrated that PGE(2) increased normal bronchial epithelial cell proliferation through induction of PDK1, an ankyrin repeat-containing Ser/Thr kinase implicated in the induction of apoptosis and the suppression of tumor growth. PDK1 siRNA and a PDK1 inhibitor blocked the effects of PGE(2) on normal cell growth. The PGE(2)-induced PDK1 expression was blocked by an antagonist of the PGE(2) receptor subtype EP4 and by EP4 siRNA. In addition, we showed that induction of PDK1 by PGE(2) was associated with induction of the transcription factor, c-Jun protein. Silencing of c-Jun using siRNA and point mutations of c-Jun sites in the PDK1 gene promoter resulted in blockade of PDK1 expression and promoter activity induced by PGE(2). In contrast, overexpression of c-Jun induced PDK1 gene promoter activity and expression followed increased cell proliferation. CONCLUSION: PGE(2) increases normal bronchial epithelial cell proliferation through increased PDK1 gene expression that is dependent on EP4 and induction of c-Jun. Therewith, our data suggest a new role of c-Jun and PDK1 in mediating epithelial cell hyperplasia induced by PGE(2).",2015 Dec 18,"['Fan, Yu', 'Wang, Ye', 'Wang, Ke']",Respir Res,,,True
25ad3917e35438350dc5fdd7f64a4a1cdaea39f9,PMC,The Vietnam Initiative on Zoonotic Infections (VIZIONS): A Strategic Approach to Studying Emerging Zoonotic Infectious Diseases,http://dx.doi.org/10.1007/s10393-015-1061-0,PMC4700077,26403795,CC BY,"The effect of newly emerging or re-emerging infectious diseases of zoonotic origin in human populations can be potentially catastrophic, and large-scale investigations of such diseases are highly challenging. The monitoring of emergence events is subject to ascertainment bias, whether at the level of species discovery, emerging disease events, or disease outbreaks in human populations. Disease surveillance is generally performed post hoc, driven by a response to recent events and by the availability of detection and identification technologies. Additionally, the inventory of pathogens that exist in mammalian and other reservoirs is incomplete, and identifying those with the potential to cause disease in humans is rarely possible in advance. A major step in understanding the burden and diversity of zoonotic infections, the local behavioral and demographic risks of infection, and the risk of emergence of these pathogens in human populations is to establish surveillance networks in populations that maintain regular contact with diverse animal populations, and to simultaneously characterize pathogen diversity in human and animal populations. Vietnam has been an epicenter of disease emergence over the last decade, and practices at the human/animal interface may facilitate the likelihood of spillover of zoonotic pathogens into humans. To tackle the scientific issues surrounding the origins and emergence of zoonotic infections in Vietnam, we have established The Vietnam Initiative on Zoonotic Infections (VIZIONS). This countrywide project, in which several international institutions collaborate with Vietnamese organizations, is combining clinical data, epidemiology, high-throughput sequencing, and social sciences to address relevant one-health questions. Here, we describe the primary aims of the project, the infrastructure established to address our scientific questions, and the current status of the project. Our principal objective is to develop an integrated approach to the surveillance of pathogens circulating in both human and animal populations and assess how frequently they are exchanged. This infrastructure will facilitate systematic investigations of pathogen ecology and evolution, enhance understanding of viral cross-species transmission events, and identify relevant risk factors and drivers of zoonotic disease emergence.",2015 Sep 24,"['Rabaa, Maia A.', 'Tue, Ngo Tri', 'Phuc, Tran My', 'Carrique-Mas, Juan', 'Saylors, Karen', 'Cotten, Matthew', 'Bryant, Juliet E.', 'Nghia, Ho Dang Trung', 'Cuong, Nguyen Van', 'Pham, Hong Anh', 'Berto, Alessandra', 'Phat, Voong Vinh', 'Dung, Tran Thi Ngoc', 'Bao, Long Hoang', 'Hoa, Ngo Thi', 'Wertheim, Heiman', 'Nadjm, Behzad', 'Monagin, Corina', 'van Doorn, H. Rogier', 'Rahman, Motiur', 'Tra, My Phan Vu', 'Campbell, James I.', 'Boni, Maciej F.', 'Tam, Pham Thi Thanh', 'van der Hoek, Lia', 'Simmonds, Peter', 'Rambaut, Andrew', 'Toan, Tran Khanh', 'Van Vinh Chau, Nguyen', 'Hien, Tran Tinh', 'Wolfe, Nathan', 'Farrar, Jeremy J.', 'Thwaites, Guy', 'Kellam, Paul', 'Woolhouse, Mark E. J.', 'Baker, Stephen']",Ecohealth,,,True
d5b1fcbc43967a2f648462695d8c0a169aed6105,PMC,Ultrastructure and lipid composition of detergent-resistant membranes derived from mammalian sperm and two types of epithelial cells,http://dx.doi.org/10.1007/s00441-015-2272-y,PMC4700079,26378009,CC BY,"Lipid rafts are micro-domains of ordered lipids (L(o) phase) in biological membranes. The L(o) phase of cellular membranes can be isolated from disordered lipids (L(d) phase) after treatment with 1 % Triton  X-100 at 4 °C in which the L(o) phase forms the detergent-resistant membrane (DRM) fraction. The lipid composition of DRM derived from Madin-Darby canine kidney (MDCK) cells, McArdle cells and porcine sperm is compared with that of the whole cell. Remarkably, the unsaturation and chain length degree of aliphatic chains attached to phospholipids is virtually the same between DRM and whole cells. Cholesterol and sphingomyelin were enriched in DRMs but to a cell-specific molar ratio. Sulfatides (sphingolipids from MDCK cells) were enriched in the DRM while a seminolipid (an alkylacylglycerolipid from sperm) was depleted from the DRM. Treatment with <5 mM methyl-ß-cyclodextrin (MBCD) caused cholesterol removal from the DRM without affecting the composition and amount of the phospholipid while higher levels disrupted the DRM. The substantial amount of (poly)unsaturated phospholipids in DRMs as well as a low stoichiometric amount of cholesterol suggest that lipid rafts in biological membranes are more fluid and dynamic than previously anticipated. Using negative staining, ultrastructural features of DRM were monitored and in all three cell types the DRMs appeared as multi-lamellar vesicular structures with a similar morphology. The detergent resistance is a result of protein–cholesterol and sphingolipid interactions allowing a relatively passive attraction of phospholipids to maintain the L(o) phase. For this special issue, the relevance of our findings is discussed in a sperm physiological context.",2016 Sep 16,"['van Gestel, Renske A.', 'Brouwers, Jos F.', 'Ultee, Anton', 'Helms, J. Bernd', 'Gadella, Bart M.']",Cell Tissue Res,,,True
0e08edfdafcee24569ce5be73cec8acb26142ba8,PMC,Recombinant Dengue virus protein NS2B alters membrane permeability in different membrane models,http://dx.doi.org/10.1186/s12985-015-0456-4,PMC4700614,26728778,CC BY,"BACKGROUND: One of the main phenomena occurring in cellular membranes during virus infection is a change in membrane permeability. It has been observed that numerous viral proteins can oligomerize and form structures known as viroporins that alter the permeability of membranes. Previous findings have identified such proteins in cells infected with Japanese encephalitis virus (JEV), a member of the same family that Dengue virus (DENV) belongs to (Flaviviridae). In the present work, we investigated whether the small hydrophobic DENV protein NS2B serves a viroporin function. METHODS: We cloned the DENV NS2B sequence and expressed it in a bacterial expression system. Subsequently, we evaluated the effect of DENV NS2B on membranes when NS2B was overexpressed, measured bacterial growth restriction, and evaluated changes of permeability to hygromycin. The NS2B protein was purified by affinity chromatography, and crosslinking assays were performed to determine the presence of oligomers. Hemolysis assays and transmission electron microscopy were performed to identify structures involved in permeability changes. RESULTS: The DENV-2 NS2B protein showed similitude with the JEV viroporin. The DENV-2 NS2B protein possessed the ability to change the membrane permeability in bacteria, to restrict bacterial cell growth, and to enable membrane permeability to hygromycin B. The NS2B protein formed trimers that could participate in cell lysis and generate organized structures on eukaryotes membranes. CONCLUSIONS: Our data suggest that the DENV-2 NS2B viral protein is capable of oligomerizing and organizing to form pore-like structures in different lipid environments, thereby modifying the permeability of cell membranes.",2016 Jan 4,"['León-Juárez, Moisés', 'Martínez-Castillo, Macario', 'Shrivastava, Gaurav', 'García-Cordero, Julio', 'Villegas-Sepulveda, Nicolás', 'Mondragón-Castelán, Mónica', 'Mondragón-Flores, Ricardo', 'Cedillo-Barrón, Leticia']",Virol J,,,True
fd19cfef82dc2fd1ee48be9b10563d681610c000,PMC,Lys-315 at the Interfaces of Diagonal Subunits of δ-Crystallin Plays a Critical Role in the Reversibility of Folding and Subunit Assembly,http://dx.doi.org/10.1371/journal.pone.0145957,PMC4701392,26731266,CC BY,"δ-Crystallin is the major structural protein in avian eye lenses and is homologous to the urea cycle enzyme argininosuccinate lyase. This protein is structurally assembled as double dimers. Lys-315 is the only residue which is arranged symmetrically at the diagonal subunit interfaces to interact with each other. This study found that wild-type protein had both dimers and monomers present in 2–4 M urea whilst only monomers of the K315A mutant were observed under the same conditions, as judged by sedimentation velocity analysis. The assembly of monomeric K315A mutant was reversible in contrast to wild-type protein. Molecular dynamics simulations showed that the dissociation of primary dimers is prior to the diagonal dimers in wild-type protein. These results suggest the critical role of Lys-315 in stabilization of the diagonal dimer structure. Guanidinium hydrochloride (GdmCl) denatured wild-type or K315A mutant protein did not fold into functional protein. However, the urea dissociated monomers of K315A mutant protein in GdmCl were reversible folding through a multiple steps mechanism as measured by tryptophan and ANS fluorescence. Two partly unfolded intermediates were detected in the pathway. Refolding of the intermediates resulted in a conformation with greater amounts of hydrophobic regions exposed which was prone to the formation of protein aggregates. The formation of aggregates was not prevented by the addition of α-crystallin. These results highlight that the conformational status of the monomers is critical for determining whether reversible oligomerization or aggregate formation occurs.",2016 Jan 5,"['Huang, Chih-Wei', 'Lin, Hui-Chen', 'Chou, Chi-Yuan', 'Kao, Wei-Chuo', 'Chou, Wei-Yuan', 'Lee, Hwei-Jen']",PLoS One,,,True
1a465d982030d8f361dc914ff2defa359fdbe5f9,PMC,The recent ancestry of Middle East respiratory syndrome coronavirus in Korea has been shaped by recombination,http://dx.doi.org/10.1038/srep18825,PMC4702133,26732651,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe cases of human respiratory disease. Since 2012, the victims have mainly come from the Middle East countries or sporadically from some other geographical regions seeded by the travelers who visited the Middle East. Such an introduction through travelling led to the emergence of a MERS-CoV outbreak in Korea in May 2015, which caused more than 140 confirmed human cases in less than a month. Using 70 complete genome sequences of MERS-CoV isolates, including the most recent sequences for the Korean and Chinese isolates, we reconstructed the phylogenetic relationships of the complete genome and the individual protein coding regions. The Korean MERS-CoV strain clustered in the previously established Hafr-Al-Batin-1_2013 clade together with two Saudi Arabian and one Chinese strain sampled in 2015. Although these four strains remained monophyletic in the entire protein-coding region, this clade showed different phylogenetic relationships across the genome, indicating a shared unique recombination pattern that is different from previously reported putative recombination strains. Our findings suggest that the recent ancestor of the Korean and its related MERS-CoV strains is characterized by unique mosaic genome pattern that is different from other putative recombinants.",2016 Jan 6,"['Kim, Jin Il', 'Kim, You-Jin', 'Lemey, Philippe', 'Lee, Ilseob', 'Park, Sehee', 'Bae, Joon-Yong', 'Kim, Donghwan', 'Kim, Hyejin', 'Jang, Seok-Il', 'Yang, Jeong-Sun', 'Kim, Hak', 'Kim, Dae-Won', 'Nam, Jeong-Gu', 'Kim, Sung Soon', 'Kim, Kisoon', 'Myun Lee, Jae', 'Song, Man Ki', 'Song, Daesub', 'Chang, Jun', 'Hong, Kee-Jong', 'Bae, Yong-Soo', 'Song, Jin-Won', 'Lee, Joo-Shil', 'Park, Man-Seong']",Sci Rep,,,True
785f1bfe60d4c4773e6492752396fc4ce8f61865,PMC,The recent ancestry of Middle East respiratory syndrome coronavirus in Korea has been shaped by recombination,http://dx.doi.org/10.1038/srep18825,PMC4702133,26732651,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe cases of human respiratory disease. Since 2012, the victims have mainly come from the Middle East countries or sporadically from some other geographical regions seeded by the travelers who visited the Middle East. Such an introduction through travelling led to the emergence of a MERS-CoV outbreak in Korea in May 2015, which caused more than 140 confirmed human cases in less than a month. Using 70 complete genome sequences of MERS-CoV isolates, including the most recent sequences for the Korean and Chinese isolates, we reconstructed the phylogenetic relationships of the complete genome and the individual protein coding regions. The Korean MERS-CoV strain clustered in the previously established Hafr-Al-Batin-1_2013 clade together with two Saudi Arabian and one Chinese strain sampled in 2015. Although these four strains remained monophyletic in the entire protein-coding region, this clade showed different phylogenetic relationships across the genome, indicating a shared unique recombination pattern that is different from previously reported putative recombination strains. Our findings suggest that the recent ancestor of the Korean and its related MERS-CoV strains is characterized by unique mosaic genome pattern that is different from other putative recombinants.",2016 Jan 6,"['Kim, Jin Il', 'Kim, You-Jin', 'Lemey, Philippe', 'Lee, Ilseob', 'Park, Sehee', 'Bae, Joon-Yong', 'Kim, Donghwan', 'Kim, Hyejin', 'Jang, Seok-Il', 'Yang, Jeong-Sun', 'Kim, Hak', 'Kim, Dae-Won', 'Nam, Jeong-Gu', 'Kim, Sung Soon', 'Kim, Kisoon', 'Myun Lee, Jae', 'Song, Man Ki', 'Song, Daesub', 'Chang, Jun', 'Hong, Kee-Jong', 'Bae, Yong-Soo', 'Song, Jin-Won', 'Lee, Joo-Shil', 'Park, Man-Seong']",Sci Rep,,,True
0ffbcddbc1c2527eca81dc62b12e587ab61ff4d0,PMC,Intubating Ebola Patients: Technical Limitations of Extensive Personal Protective Equipment,http://dx.doi.org/10.5811/westjem.2015.10.28779,PMC4703159,26759639,CC BY,,2015 Dec 14,"['Wiechmann, Warren', 'Toohey, Shannon', 'Majestic, Cassandra', 'Boysen-Osborn, Megan']",West J Emerg Med,,,True
d4d885e748fc8335d359da08f2ef0370103f98c7,PMC,A general strategy to inhibiting viral −1 frameshifting based on upstream attenuation duplex formation,http://dx.doi.org/10.1093/nar/gkv1307,PMC4705660,26612863,CC BY,"Viral −1 programmed ribosomal frameshifting (PRF) as a potential antiviral target has attracted interest because many human viral pathogens, including human immunodeficiency virus (HIV) and coronaviruses, rely on −1 PRF for optimal propagation. Efficient eukaryotic −1 PRF requires an optimally placed stimulator structure downstream of the frameshifting site and different strategies targeting viral −1 PRF stimulators have been developed. However, accessing particular −1 PRF stimulator information represents a bottle-neck in combating the emerging epidemic viral pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV). Recently, an RNA hairpin upstream of frameshifting site was shown to act as a cis-element to attenuate −1 PRF with mechanism unknown. Here, we show that an upstream duplex formed in-trans, by annealing an antisense to its complementary mRNA sequence upstream of frameshifting site, can replace an upstream hairpin to attenuate −1 PRF efficiently. This finding indicates that the formation of a proximal upstream duplex is the main determining factor responsible for −1 PRF attenuation and provides mechanistic insight. Additionally, the antisense-mediated upstream duplex approach downregulates −1 PRF stimulated by distinct −1 PRF stimulators, including those of MERS-CoV, suggesting its general application potential as a robust means to evaluating viral −1 PRF inhibition as soon as the sequence information of an emerging human coronavirus is available.",2016 Jan 8,"['Hu, Hao-Teng', 'Cho, Che-Pei', 'Lin, Ya-Hui', 'Chang, Kung-Yao']",Nucleic Acids Res,,,True
8d9c4ed5074e68cc26a911f277ad05fa0cd7c0e7,PMC,A general strategy to inhibiting viral −1 frameshifting based on upstream attenuation duplex formation,http://dx.doi.org/10.1093/nar/gkv1307,PMC4705660,26612863,CC BY,"Viral −1 programmed ribosomal frameshifting (PRF) as a potential antiviral target has attracted interest because many human viral pathogens, including human immunodeficiency virus (HIV) and coronaviruses, rely on −1 PRF for optimal propagation. Efficient eukaryotic −1 PRF requires an optimally placed stimulator structure downstream of the frameshifting site and different strategies targeting viral −1 PRF stimulators have been developed. However, accessing particular −1 PRF stimulator information represents a bottle-neck in combating the emerging epidemic viral pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV). Recently, an RNA hairpin upstream of frameshifting site was shown to act as a cis-element to attenuate −1 PRF with mechanism unknown. Here, we show that an upstream duplex formed in-trans, by annealing an antisense to its complementary mRNA sequence upstream of frameshifting site, can replace an upstream hairpin to attenuate −1 PRF efficiently. This finding indicates that the formation of a proximal upstream duplex is the main determining factor responsible for −1 PRF attenuation and provides mechanistic insight. Additionally, the antisense-mediated upstream duplex approach downregulates −1 PRF stimulated by distinct −1 PRF stimulators, including those of MERS-CoV, suggesting its general application potential as a robust means to evaluating viral −1 PRF inhibition as soon as the sequence information of an emerging human coronavirus is available.",2016 Jan 8,"['Hu, Hao-Teng', 'Cho, Che-Pei', 'Lin, Ya-Hui', 'Chang, Kung-Yao']",Nucleic Acids Res,,,True
fb2c5faf4ed6df2563f6f1830de5b7fbad0ead87,PMC,Clinical features of children hospitalized with influenza A and B infections during the 2012–2013 influenza season in Italy,http://dx.doi.org/10.1186/s12879-015-1333-x,PMC4705698,26743673,CC BY,"BACKGROUND: Influenza is a major public health issue worldwide. It is characterized by episodes of infection that involve hundreds of millions of people each year. Since that in the seasons 2010–2011 and 2011–2012 the circulation of FLUB was decreasing we evaluated the clinical presentation, demographic characteristics, admitting department, and length of stay in children who contracted influenza admitted to Bambino Gesù Children’s Hospital, during the 2012–2013 influenza season, with the aim to establish if the recover of FLUB was associated to a clinical worsening, in comparison with those due to FLUA. METHODS: A total of 133 respiratory specimens, collected from patients with symptoms of respiratory tract infections, positive for the Influenza A and B viruses (FLUA and B) were subtyped. Comparisons between the FLUA and FLUB groups were performed with the one-way ANOVA for continuous parametric variables, the Mann-Whitney test for non-parametric variables, or the Chi-Square test or Fisher’s exact test (if cells <5) for categorical variables. RESULTS: 87.09 % of the FLUA isolates were the H1N1 subtype and 12.90 % were H3N2. Among the FLUB isolates, 91.54 % were the B/Yamagata/16/88 lineage and 8.45 % were the B/Victoria/02/87 lineage. The largest number of FLUA/H1N1 cases was observed in children less than 1 years old, while the B/Yamagata/16/88 lineage was most prevalent in children 3–6 years old. Fever was a common symptom for both FLUA and B affected patients. However, respiratory symptoms were more prevalent in patients affected by FLUA. The median length of stay in the hospital was 5 days for FLUA and 3 days for FLUB. CONCLUSIONS: The clinical features correlated to different Influenza viruses, and relevant subtypes, were evaluated concluding that the increasing of FLUB in the season 2012–2013 was without any dramatic change in clinical manifestation. Our findings suggest, finally, that a stronger commitment to managing patients affected by FLUA is required, as the disease is more severe than FLUB.",2016 Jan 8,"['Mancinelli, Livia', 'Onori, Manuela', 'Concato, Carlo', 'Sorge, Roberto', 'Chiavelli, Stefano', 'Coltella, Luana', 'Raucci, Umberto', 'Reale, Antonio', 'Menichella, Donato', 'Russo, Cristina']",BMC Infect Dis,,,True
593333395be3bd94387b4e273cc8ed13b398d5c0,PMC,Deletion of Dystrophin In-Frame Exon 5 Leads to a Severe Phenotype: Guidance for Exon Skipping Strategies,http://dx.doi.org/10.1371/journal.pone.0145620,PMC4706350,26745801,CC BY,"Duchenne and Becker muscular dystrophy severity depends upon the nature and location of the DMD gene lesion and generally correlates with the dystrophin open reading frame. However, there are striking exceptions where an in-frame genomic deletion leads to severe pathology or protein-truncating mutations (nonsense or frame-shifting indels) manifest as mild disease. Exceptions to the dystrophin reading frame rule are usually resolved after molecular diagnosis on muscle RNA. We report a moderate/severe Becker muscular dystrophy patient with an in-frame genomic deletion of DMD exon 5. This mutation has been reported by others as resulting in Duchenne or Intermediate muscular dystrophy, and the loss of this in-frame exon in one patient led to multiple splicing events, including omission of exon 6, that disrupts the open reading frame and is consistent with a severe phenotype. The patient described has a deletion of dystrophin exon 5 that does not compromise recognition of exon 6, and although the deletion does not disrupt the reading frame, his clinical presentation is more severe than would be expected for classical Becker muscular dystrophy. We suggest that the dystrophin isoform lacking the actin-binding sequence encoded by exon 5 is compromised, reflected by the phenotype resulting from induction of this dystrophin isoform in mouse muscle in vivo. Hence, exon skipping to address DMD-causing mutations within DMD exon 5 may not yield an isoform that confers marked clinical benefit. Additional studies will be required to determine whether multi-exon skipping strategies could yield more functional dystrophin isoforms, since some BMD patients with larger in-frame deletions in this region have been reported with mild phenotypes.",2016 Jan 8,"['Toh, Zhi Yon Charles', 'Thandar Aung-Htut, May', 'Pinniger, Gavin', 'Adams, Abbie M.', 'Krishnaswarmy, Sudarsan', 'Wong, Brenda L.', 'Fletcher, Sue', 'Wilton, Steve D.']",PLoS One,,,True
b2fc5ae2867a0bc478fbd993c240bd7e59531e66,PMC,Self-assembling protein nanoparticles in the design of vaccines,http://dx.doi.org/10.1016/j.csbj.2015.11.001,PMC4706605,26862374,CC BY,"For over 100 years, vaccines have been one of the most effective medical interventions for reducing infectious disease, and are estimated to save millions of lives globally each year. Nevertheless, many diseases are not yet preventable by vaccination. This large unmet medical need demands further research and the development of novel vaccines with high efficacy and safety. Compared to the 19th and early 20th century vaccines that were made of killed, inactivated, or live-attenuated pathogens, modern vaccines containing isolated, highly purified antigenic protein subunits are safer but tend to induce lower levels of protective immunity. One strategy to overcome the latter is to design antigen nanoparticles: assemblies of polypeptides that present multiple copies of subunit antigens in well-ordered arrays with defined orientations that can potentially mimic the repetitiveness, geometry, size, and shape of the natural host-pathogen surface interactions. Such nanoparticles offer a collective strength of multiple binding sites (avidity) and can provide improved antigen stability and immunogenicity. Several exciting advances have emerged lately, including preclinical evidence that this strategy may be applicable for the development of innovative new vaccines, for example, protecting against influenza, human immunodeficiency virus, and respiratory syncytial virus. Here, we provide a concise review of a critical selection of data that demonstrate the potential of this field. In addition, we highlight how the use of self-assembling protein nanoparticles can be effectively combined with the emerging discipline of structural vaccinology for maximum impact in the rational design of vaccine antigens.",2015 Nov 26,"['López-Sagaseta, Jacinto', 'Malito, Enrico', 'Rappuoli, Rino', 'Bottomley, Matthew J.']",Comput Struct Biotechnol J,,,False
de9de0c48a6efdb714e714907ec3cff924dd28a5,PMC,Hemagglutinin-esterase-fusion (HEF) protein of influenza C virus,http://dx.doi.org/10.1007/s13238-015-0193-x,PMC4707155,26215728,CC BY,"Influenza C virus, a member of the Orthomyxoviridae family, causes flu-like disease but typically only with mild symptoms. Humans are the main reservoir of the virus, but it also infects pigs and dogs. Very recently, influenza C-like viruses were isolated from pigs and cattle that differ from classical influenza C virus and might constitute a new influenza virus genus. Influenza C virus is unique since it contains only one spike protein, the hemagglutinin-esterase-fusion glycoprotein HEF that possesses receptor binding, receptor destroying and membrane fusion activities, thus combining the functions of Hemagglutinin (HA) and Neuraminidase (NA) of influenza A and B viruses. Here we briefly review the epidemiology and pathology of the virus and the morphology of virus particles and their genome. The main focus is on the structure of the HEF protein as well as on its co- and post-translational modification, such as N-glycosylation, disulfide bond formation, S-acylation and proteolytic cleavage into HEF1 and HEF2 subunits. Finally, we describe the functions of HEF: receptor binding, esterase activity and membrane fusion. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-015-0193-x) contains supplementary material, which is available to authorized users.",2016 Jan 28,"['Wang, Mingyang', 'Veit, Michael']",Protein Cell,,,False
4d140ee8fb10afd86c19fc5ad4749771dc37d146,PMC,Hemagglutinin-esterase-fusion (HEF) protein of influenza C virus,http://dx.doi.org/10.1007/s13238-015-0193-x,PMC4707155,26215728,CC BY,"Influenza C virus, a member of the Orthomyxoviridae family, causes flu-like disease but typically only with mild symptoms. Humans are the main reservoir of the virus, but it also infects pigs and dogs. Very recently, influenza C-like viruses were isolated from pigs and cattle that differ from classical influenza C virus and might constitute a new influenza virus genus. Influenza C virus is unique since it contains only one spike protein, the hemagglutinin-esterase-fusion glycoprotein HEF that possesses receptor binding, receptor destroying and membrane fusion activities, thus combining the functions of Hemagglutinin (HA) and Neuraminidase (NA) of influenza A and B viruses. Here we briefly review the epidemiology and pathology of the virus and the morphology of virus particles and their genome. The main focus is on the structure of the HEF protein as well as on its co- and post-translational modification, such as N-glycosylation, disulfide bond formation, S-acylation and proteolytic cleavage into HEF1 and HEF2 subunits. Finally, we describe the functions of HEF: receptor binding, esterase activity and membrane fusion. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-015-0193-x) contains supplementary material, which is available to authorized users.",2016 Jan 28,"['Wang, Mingyang', 'Veit, Michael']",Protein Cell,,,True
1771673809c10324fde2768ce37d548a5077577f,PMC,"Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits",http://dx.doi.org/10.1371/journal.pone.0146932,PMC4709053,26752173,CC BY,"Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply.",2016 Jan 11,"['Gruse, Jeannine', 'Kanitz, Ellen', 'Weitzel, Joachim M.', 'Tuchscherer, Armin', 'Stefaniak, Tadeusz', 'Jawor, Paulina', 'Wolffram, Siegfried', 'Hammon, Harald M.']",PLoS One,,,True
70b06768370d7d7c63a8f9a5042f67f8d9d02cf5,PMC,"Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits",http://dx.doi.org/10.1371/journal.pone.0146932,PMC4709053,26752173,CC BY,"Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply.",2016 Jan 11,"['Gruse, Jeannine', 'Kanitz, Ellen', 'Weitzel, Joachim M.', 'Tuchscherer, Armin', 'Stefaniak, Tadeusz', 'Jawor, Paulina', 'Wolffram, Siegfried', 'Hammon, Harald M.']",PLoS One,,,False
dbd179cd05bcab8d52bcea618633deb27b6067b7,PMC,"Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits",http://dx.doi.org/10.1371/journal.pone.0146932,PMC4709053,26752173,CC BY,"Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply.",2016 Jan 11,"['Gruse, Jeannine', 'Kanitz, Ellen', 'Weitzel, Joachim M.', 'Tuchscherer, Armin', 'Stefaniak, Tadeusz', 'Jawor, Paulina', 'Wolffram, Siegfried', 'Hammon, Harald M.']",PLoS One,,,False
39b7779027ca766d010009b54455331929b42d65,PMC,"Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits",http://dx.doi.org/10.1371/journal.pone.0146932,PMC4709053,26752173,CC BY,"Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply.",2016 Jan 11,"['Gruse, Jeannine', 'Kanitz, Ellen', 'Weitzel, Joachim M.', 'Tuchscherer, Armin', 'Stefaniak, Tadeusz', 'Jawor, Paulina', 'Wolffram, Siegfried', 'Hammon, Harald M.']",PLoS One,,,False
41d4cb748a87a5bdd92a314aceea03950f8d7849,PMC,"Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits",http://dx.doi.org/10.1371/journal.pone.0146932,PMC4709053,26752173,CC BY,"Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply.",2016 Jan 11,"['Gruse, Jeannine', 'Kanitz, Ellen', 'Weitzel, Joachim M.', 'Tuchscherer, Armin', 'Stefaniak, Tadeusz', 'Jawor, Paulina', 'Wolffram, Siegfried', 'Hammon, Harald M.']",PLoS One,,,False
3322a97885dd968ef3ca3dfc0e729f4206317afc,PMC,"Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits",http://dx.doi.org/10.1371/journal.pone.0146932,PMC4709053,26752173,CC BY,"Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply.",2016 Jan 11,"['Gruse, Jeannine', 'Kanitz, Ellen', 'Weitzel, Joachim M.', 'Tuchscherer, Armin', 'Stefaniak, Tadeusz', 'Jawor, Paulina', 'Wolffram, Siegfried', 'Hammon, Harald M.']",PLoS One,,,False
f475fa6896d258457c8552fa960533b237ff7f18,PMC,"Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits",http://dx.doi.org/10.1371/journal.pone.0146932,PMC4709053,26752173,CC BY,"Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply.",2016 Jan 11,"['Gruse, Jeannine', 'Kanitz, Ellen', 'Weitzel, Joachim M.', 'Tuchscherer, Armin', 'Stefaniak, Tadeusz', 'Jawor, Paulina', 'Wolffram, Siegfried', 'Hammon, Harald M.']",PLoS One,,,False
58a0105289bbee3214a3fe6494ba86fce867df3a,PMC,Heterologous Immunity between Adenoviruses and Hepatitis C Virus: A New Paradigm in HCV Immunity and Vaccines,http://dx.doi.org/10.1371/journal.pone.0146404,PMC4709057,26751211,CC BY,"Adenoviruses (Ad) are commonly used as vectors for gene therapy and/or vaccine delivery. Recombinant Ad vectors are being tested as vaccines for many pathogens. We have made a surprising observation that peptides derived from various hepatitis C virus (HCV) antigens contain extensive regions of homology with multiple adenovirus proteins, and conclusively demonstrate that adenovirus vector can induce robust, heterologous cellular and humoral immune responses against multiple HCV antigens. Intriguingly, the induction of this cross-reactive immunity leads to significant reduction of viral loads in a recombinant vaccinia-HCV virus infected mouse model, supporting their role in antiviral immunity against HCV. Healthy human subjects with Ad-specific pre-existing immunity demonstrated cross-reactive cellular and humoral immune responses against multiple HCV antigens. These findings reveal the potential of a previously uncharacterized property of natural human adenovirus infection to dictate, modulate and/or alter the course of HCV infection upon exposure. This intrinsic property of adenovirus vectors to cross-prime HCV immunity can also be exploited to develop a prophylactic and/or therapeutic vaccine against HCV.",2016 Jan 11,"['Singh, Shakti', 'Vedi, Satish', 'Samrat, Subodh Kumar', 'Li, Wen', 'Kumar, Rakesh', 'Agrawal, Babita']",PLoS One,,,True
0e261abc97b50372753a8415e5a6b12da8a6be05,PMC,Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats,http://dx.doi.org/10.7554/eLife.11785,PMC4709267,26698106,CC0,"Biological factors that influence the host range and spillover of Ebola virus (EBOV) and other filoviruses remain enigmatic. While filoviruses infect diverse mammalian cell lines, we report that cells from African straw-colored fruit bats (Eidolon helvum) are refractory to EBOV infection. This could be explained by a single amino acid change in the filovirus receptor, NPC1, which greatly reduces the affinity of EBOV-NPC1 interaction. We found signatures of positive selection in bat NPC1 concentrated at the virus-receptor interface, with the strongest signal at the same residue that controls EBOV infection in Eidolon helvum cells. Our work identifies NPC1 as a genetic determinant of filovirus susceptibility in bats, and suggests that some NPC1 variations reflect host adaptations to reduce filovirus replication and virulence. A single viral mutation afforded escape from receptor control, revealing a pathway for compensatory viral evolution and a potential avenue for expansion of filovirus host range in nature. DOI: http://dx.doi.org/10.7554/eLife.11785.001",,"['Ng, Melinda', 'Ndungo, Esther', 'Kaczmarek, Maria E', 'Herbert, Andrew S', 'Binger, Tabea', 'Kuehne, Ana I', 'Jangra, Rohit K', 'Hawkins, John A', 'Gifford, Robert J', 'Biswas, Rohan', 'Demogines, Ann', 'James, Rebekah M', 'Yu, Meng', 'Brummelkamp, Thijn R', 'Drosten, Christian', 'Wang, Lin-Fa', 'Kuhn, Jens H', 'Müller, Marcel A', 'Dye, John M', 'Sawyer, Sara L', 'Chandran, Kartik']",eLife.; 4:e11785,,,True
aa080b8ad0bb2c4cd4e24f407b32f0e837c27432,PMC,Exogenous avian leukosis virus-induced activation of the ERK/AP1 pathway is required for virus replication and correlates with virus-induced tumorigenesis,http://dx.doi.org/10.1038/srep19226,PMC4709637,26754177,CC BY,"A proteomics approach was used to reveal the up-regulated proteins involved in the targeted mitogen-activated protein kinase (MAPK) signal transduction pathway in DF-1 cells after ALV subgroup J (ALV-J) infection. Next, we found that ALV-J CHN06 strain infection of DF-1 cells correlated with extracellular signal-regulated kinase 2 (ERK2) activation, which was mainly induced within 15 min, a very early stage of infection, and at a late infection stage, from 108 h to 132 h post-infection. Infection with other ALV subgroup (A/B) strains also triggered ERK/MAPK activation. Moreover, when activating ERK2, ALV subgroups A, B and J simultaneously induced the phosphorylation of c-Jun, an AP1 family member and p38 activation but had no obvious effect on JNK activation at either 15 min or 120 h. Interestingly, only PD98059 inhibited the ALV-induced c-Jun phosphorylation while SP600125 or SB203580 had no influence on c-Jun activation. Furthermore, the viral gp85 and gag proteins were found to contribute to ERK2/AP1 activation. Additionally, the specific ERK inhibitor, PD980509, significantly suppressed ALV replication, as evidenced by extremely low levels of ALV promoter activity and ALV-J protein expression. In vivo analysis of ERK2 activation in tumor cells derived from ALV-J-infected chicken demonstrated a strong correlation between ERK/MAPK activation and virus-associated tumorigenesis.",2016 Jan 12,"['Dai, Manman', 'Feng, Min', 'Ye, Yu', 'Wu, Xiaochan', 'Liu, Di', 'Liao, Ming', 'Cao, Weisheng']",Sci Rep,,,True
7c3ebae910203c1f867fad1b2c14c555fc3e263c,PMC,Crude incidence in two-phase designs in the presence of competing risks,http://dx.doi.org/10.1186/s12874-015-0103-1,PMC4710022,26754746,CC BY,"BACKGROUND: In many studies, some information might not be available for the whole cohort, some covariates, or even the outcome, might be ascertained in selected subsamples. These studies are part of a broad category termed two-phase studies. Common examples include the nested case-control and the case-cohort designs. For two-phase studies, appropriate weighted survival estimates have been derived; however, no estimator of cumulative incidence accounting for competing events has been proposed. This is relevant in the presence of multiple types of events, where estimation of event type specific quantities are needed for evaluating outcome. METHODS: We develop a non parametric estimator of the cumulative incidence function of events accounting for possible competing events. It handles a general sampling design by weights derived from the sampling probabilities. The variance is derived from the influence function of the subdistribution hazard. RESULTS: The proposed method shows good performance in simulations. It is applied to estimate the crude incidence of relapse in childhood acute lymphoblastic leukemia in groups defined by a genotype not available for everyone in a cohort of nearly 2000 patients, where death due to toxicity acted as a competing event. In a second example the aim was to estimate engagement in care of a cohort of HIV patients in resource limited setting, where for some patients the outcome itself was missing due to lost to follow-up. A sampling based approach was used to identify outcome in a subsample of lost patients and to obtain a valid estimate of connection to care. CONCLUSIONS: A valid estimator for cumulative incidence of events accounting for competing risks under a general sampling design from an infinite target population is derived.",2016 Jan 11,"['Rebora, Paola', 'Antolini, Laura', 'Glidden, David V.', 'Valsecchi, Maria Grazia']",BMC Med Res Methodol,,,True
e4e1a4d2d3384d9abc48576bb31cdb9c497732fb,PMC,Case–control study of pathogens involved in piglet diarrhea,http://dx.doi.org/10.1186/s13104-015-1751-2,PMC4710041,26754836,CC BY,"BACKGROUND: Diarrhea in piglets directly affects commercial swine production. The disease results from the interaction of pathogens with the host immune system and is also affected by management procedures. Several pathogenic agents such as Campylobacter spp., Clostridium perfringens, Escherichia coli, Salmonella spp., group A rotavirus (RV-A), coronaviruses (transmissible gastroenteritis virus; porcine epidemic diarrhea virus), as well as nematode and protozoan parasites, can be associated with disease cases. RESULTS: All bacterial, viral, protozoan, and parasitic agents here investigated, with the exception of Salmonella spp. as well as both coronaviruses, were detected in varying proportions in piglet fecal samples, and positive animals were equally distributed between case and control groups. A statistically significant difference between case and control groups was found only for Cystoisospora suis (p = 0.034) and Eimeria spp. (p = 0.047). When co-infections were evaluated, a statistically significant difference was found only for C. perfringens β2 and C. suis (p = 0.014). CONCLUSIONS: The presence of pathogens in piglets alone does not determine the occurrence of diarrhea episodes. Thus, the indiscriminate use of antibiotic and anthelminthic medication should be re-evaluated. This study also reinforces the importance of laboratory diagnosis and correct interpretation of results as well as the relevance of control and prophylactic measures.",2016 Jan 11,"['Ruiz, Vera L. A.', 'Bersano, Josete G.', 'Carvalho, Aline F.', 'Catroxo, Márcia H. B.', 'Chiebao, Daniela P.', 'Gregori, Fábio', 'Miyashiro, Simone', 'Nassar, Alessandra F. C.', 'Oliveira, Trícia M. F. S.', 'Ogata, Renato A.', 'Scarcelli, Eliana P.', 'Tonietti, Paloma O.']",BMC Res Notes,,,True
65731cfe4b5e1d05aa7c85d3b088346832c35315,PMC,Real-Time Reverse Transcription PCR Assay for Detection of Senecavirus A in Swine Vesicular Diagnostic Specimens,http://dx.doi.org/10.1371/journal.pone.0146211,PMC4710529,26757142,CC0,"Senecavirus A (SV-A), formerly, Seneca Valley virus (SVV), has been detected in swine with vesicular lesions and is thought to be associated with swine idiopathic vesicular disease (SIVD), a vesicular disease syndrome that lacks a defined causative agent. The clinical presentation of SIVD resembles that of other more contagious and economically devastating vesicular diseases, such as foot-and-mouth disease (FMD), swine vesicular disease (SVD), and vesicular stomatitis (VS), that typically require immediate rule out diagnostics to lift restrictions on animal quarantine, movement, and trade. This study presents the development of a sensitive, SYBR Green RT-qPCR assay suitable for detection of SV-A in diagnostic swine specimens. After testing 50 pigs with clinical signs consistent with vesicular disease, 44 (88%) were found to be positive for SV-A by RT-qPCR as compared to none from a negative cohort of 35 animals without vesicular disease, indicating that the assay is able to successfully detect the virus in an endemic population. SV-A RNA was also detectable at a low level in sera from a subset of pigs that presented with (18%) or without (6%) vesicular signs. In 2015, there has been an increase in the occurrence of SV-A in the US, and over 200 specimens submitted to our laboratory for vesicular investigation have tested positive for the virus using this method. SV-A RNA was detectable in all common types of vesicular specimens including swabs and tissue from hoof lesions, oral and snout epithelium, oral swabs, scabs, and internal organ tissues such as liver and lymph node. Genome sequencing analysis from recent virus isolates was performed to confirm target amplicon specificity and was aligned to previous isolates.",2016 Jan 12,"['Bracht, Alexa J.', 'O’Hearn, Emily S.', 'Fabian, Andrew W.', 'Barrette, Roger W.', 'Sayed, Abu']",PLoS One,,,True
8b17b1580dd61644c73c3c579212f45640cd107c,PMC,The leukocyte-stiffening property of plasma in early acute respiratory distress syndrome (ARDS) revealed by a microfluidic single-cell study: the role of cytokines and protection with antibodies,http://dx.doi.org/10.1186/s13054-015-1157-5,PMC4711060,26757701,CC BY,"BACKGROUND: Leukocyte-mediated pulmonary inflammation is a key pathophysiological mechanism involved in acute respiratory distress syndrome (ARDS). Massive sequestration of leukocytes in the pulmonary microvasculature is a major triggering event of the syndrome. We therefore investigated the potential role of leukocyte stiffness and adhesiveness in the sequestration of leukocytes in microvessels.  METHODS: This study was based on in vitro microfluidic assays using patient sera. Cell stiffness was assessed by measuring the entry time (ET) of a single cell into a microchannel with a 6 × 9–μm cross-section under a constant pressure drop (ΔP = 160 Pa). Primary neutrophils and monocytes, as well as the monocytic THP-1 cell line, were used. Cellular adhesiveness to human umbilical vein endothelial cells was examined using the laminar flow chamber method. We compared the properties of cells incubated with the sera of healthy volunteers (n = 5), patients presenting with acute cardiogenic pulmonary edema (ACPE; n = 6), and patients with ARDS (n = 22), of whom 13 were classified as having moderate to severe disease and the remaining 9 as having mild disease.  RESULTS: Rapid and strong stiffening of primary neutrophils and monocytes was induced within 30 minutes (mean ET >50 seconds) by sera from the ARDS group compared with both the healthy subjects and the ACPE groups (mean ET <1 second) (p < 0.05). Systematic measurements with the THP-1 cell line allowed for the establishment of a strong correlation between stiffening and the severity of respiratory status (mean ET 0.82 ± 0.08 seconds for healthy subjects, 1.6 ± 1.0 seconds for ACPE groups, 10.5 ± 6.1 seconds for mild ARDS, and 20.0 ± 8.1 seconds for moderate to severe ARDS; p < 0.05). Stiffening correlated with the cytokines interleukin IL-1β, IL-8, tumor necrosis factor TNF-α, and IL-10 but not with interferon-γ, transforming growth factor-β, IL-6, or IL-17. Strong stiffening was induced by IL-1β, IL-8, and TNF-α but not by IL-10, and incubations with sera and blocking antibodies against IL-1β, IL-8, or TNF-α significantly diminished the stiffening effect of serum. In contrast, the measurements of integrin expression (CD11b, CD11a, CD18, CD49d) and leukocyte–endothelium adhesion showed a weak and slow response after incubation with the sera of patients with ARDS (several hours), suggesting a lesser role of leukocyte adhesiveness compared with leukocyte stiffness in early ARDS.  CONCLUSIONS: The leukocyte stiffening induced by cytokines in the sera of patients might play a role in the sequestration of leukocytes in the lung capillary beds during early ARDS. The inhibition of leukocyte stiffening with blocking antibodies might inspire future therapeutic strategies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-1157-5) contains supplementary material, which is available to authorized users.",2016 Jan 12,"['Preira, Pascal', 'Forel, Jean-Marie', 'Robert, Philippe', 'Nègre, Paulin', 'Biarnes-Pelicot, Martine', 'Xeridat, Francois', 'Bongrand, Pierre', 'Papazian, Laurent', 'Theodoly, Olivier']",Crit Care,,,True
1ccf19a7957dd88ddcce92605007ad16f26d28ed,PMC,Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger,http://dx.doi.org/10.1371/journal.ppat.1005373,PMC4711667,26730950,CC BY,"Ebola virus (EBOV) is a highly pathogenic filovirus that causes hemorrhagic fever in humans and animals. Currently, how EBOV fuses its envelope membrane within an endosomal membrane to cause infection is poorly understood. We successfully measure cell-cell fusion mediated by the EBOV fusion protein, GP, assayed by the transfer of both cytoplasmic and membrane dyes. A small molecule fusion inhibitor, a neutralizing antibody, as well as mutations in EBOV GP known to reduce viral infection, all greatly reduce fusion. By monitoring redistribution of small aqueous dyes between cells and by electrical capacitance measurements, we discovered that EBOV GP-mediated fusion pores do not readily enlarge—a marked difference from the behavior of other viral fusion proteins. EBOV GP must be cleaved by late endosome-resident cathepsins B or L in order to become fusion-competent. Cleavage of cell surface-expressed GP appears to occur in endosomes, as evidenced by the fusion block imposed by cathepsin inhibitors, agents that raise endosomal pH, or an inhibitor of anterograde trafficking. Treating effector cells with a recombinant soluble cathepsin B or thermolysin, which cleaves GP into an active form, increases the extent of fusion, suggesting that a fraction of surface-expressed GP is not cleaved. Whereas the rate of fusion is increased by a brief exposure to acidic pH, fusion does occur at neutral pH. Importantly, the extent of fusion is independent of external pH in experiments in which cathepsin activity is blocked and EBOV GP is cleaved by thermolysin. These results imply that low pH promotes fusion through the well-known pH-dependent activity of cathepsins; fusion induced by cleaved EBOV GP is a process that is fundamentally independent of pH. The cell-cell fusion system has revealed some previously unappreciated features of EBOV entry, which could not be readily elucidated in the context of endosomal entry.",2016 Jan 5,"['Markosyan, Ruben M.', 'Miao, Chunhui', 'Zheng, Yi-Min', 'Melikyan, Gregory B.', 'Liu, Shan-Lu', 'Cohen, Fredric S.']",PLoS Pathog,,,True
0304ed96b29c38014a17bacefcc294a02c04d0a0,PMC,Statistical Evaluation of HTS Assays for Enzymatic Hydrolysis of β-Keto Esters,http://dx.doi.org/10.1371/journal.pone.0146104,PMC4711668,26730596,CC BY,"β-keto esters are used as precursors for the synthesis of β-amino acids, which are building blocks for some classes of pharmaceuticals. Here we describe the comparison of screening procedures for hydrolases to be used for the hydrolysis of β-keto esters, the first step in the preparation of β-amino acids. Two of the tested high throughput screening (HTS) assays depend on coupled enzymatic reactions which detect the alcohol released during ester hydrolysis by luminescence or absorption. The third assay detects the pH shift due to acid formation using an indicator dye. To choose the most efficient approach for screening, we assessed these assays with different statistical methods—namely, the classical Z’-factor, standardized mean difference (SSMD), the Kolmogorov-Smirnov-test, and t-statistics. This revealed that all three assays are suitable for HTS, the pH assay performing best. Based on our data we discuss the explanatory power of different statistical measures. Finally, we successfully employed the pH assay to identify a very fast hydrolase in an enzyme-substrate screening.",2016 Jan 5,"['Buß, O.', 'Jager, S.', 'Dold, S. -M.', 'Zimmermann, S.', 'Hamacher, K.', 'Schmitz, K.', 'Rudat, J.']",PLoS One,,,True
a8adfbfaece0694336909eceb6fa3ed7e737ae9e,PMC,Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome,http://dx.doi.org/10.1371/journal.pone.0145694,PMC4712828,26745868,CC BY,"OBJECTIVE: It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS. METHODS: Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAP(SB)) and abdominal muscle paralysis group (BIPAP(AP)). All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH(2)O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO(2) of 35–60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV) and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment. RESULTS: For the comparable ventilator setting, as compared with BIPAP(SB) group, the BIPAP(AP) group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAP(AP) group (22.5±2.0 vs. 25.2±2.1). CONCLUSION: Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.",2016 Jan 8,"['Zhang, Xianming', 'Wu, Weiliang', 'Zhu, Yongcheng', 'Jiang, Ying', 'Du, Juan', 'Chen, Rongchang']",PLoS One,,,True
ad3ad574d436dbb8cb39de496b123c05588b3af9,PMC,Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome,http://dx.doi.org/10.1371/journal.pone.0145694,PMC4712828,26745868,CC BY,"OBJECTIVE: It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS. METHODS: Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAP(SB)) and abdominal muscle paralysis group (BIPAP(AP)). All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH(2)O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO(2) of 35–60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV) and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment. RESULTS: For the comparable ventilator setting, as compared with BIPAP(SB) group, the BIPAP(AP) group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAP(AP) group (22.5±2.0 vs. 25.2±2.1). CONCLUSION: Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.",2016 Jan 8,"['Zhang, Xianming', 'Wu, Weiliang', 'Zhu, Yongcheng', 'Jiang, Ying', 'Du, Juan', 'Chen, Rongchang']",PLoS One,,,False
360028f9b31d57ec6bbffa2c66602434f012f167,PMC,Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome,http://dx.doi.org/10.1371/journal.pone.0145694,PMC4712828,26745868,CC BY,"OBJECTIVE: It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS. METHODS: Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAP(SB)) and abdominal muscle paralysis group (BIPAP(AP)). All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH(2)O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO(2) of 35–60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV) and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment. RESULTS: For the comparable ventilator setting, as compared with BIPAP(SB) group, the BIPAP(AP) group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAP(AP) group (22.5±2.0 vs. 25.2±2.1). CONCLUSION: Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.",2016 Jan 8,"['Zhang, Xianming', 'Wu, Weiliang', 'Zhu, Yongcheng', 'Jiang, Ying', 'Du, Juan', 'Chen, Rongchang']",PLoS One,,,False
968d0b07b0b65a15cedfd2357e3ba9649742836e,PMC,Novel treatment of severe combined immunodeficiency utilizing ex-vivo T-cell depleted haploidentical hematopoietic stem cell transplantation and CD45RA+ depleted donor lymphocyte infusions,http://dx.doi.org/10.1186/s13023-016-0385-3,PMC4714422,26768987,CC BY,"BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment available for severe combined immunodeficiency (SCID); although, there is a high incidence of severe infections and an increased risk of graft-versus host-disease (GvHD) with HSCT. Early intervention is a crucial prognostic factor and a HLA-haploidentical parental donor is often available. Haploidentical HSCT protocols utilizing extensively ex vivo T-cell depleted grafts (CliniMACs system) have proven efficient in preventing GvHD, but cause a delay in early T-cell recovery that increases the risk of viral infections. Here, we present a novel approach for treating SCID that combines selective depletion of GvHD-inducing alpha/beta (α/β) T-cells from the haploidentical HSCT graft with a subsequent donor lymphocyte infusion (DLI) enriched for CD45RO+ memory T-cells. RESULTS: Our patient was diagnosed with SCID (T-B + NK+ phenotype). At 9 months of age, he received a T cell receptor(TCR)α/β-cell depleted graft from his haploidentical mother, following a reduced intensity conditioning regimen with no additional GvHD prophylaxis. Engraftment was rapid with complete donor chimerism and no signs of GvHD. However, at 12 weeks post HSCT, the patient was still T-cell lymphopenic with clinical symptoms of multiple severe viral infections. Consequently, therapeutic DLIs were initiated for enhanced anti-viral immunity. The patient was treated with CD45RA+ depleted haploidentical maternal donor lymphocytes enriched from unmobilized whole blood, and a total T-cell dose of no more than 25 x10(3) CD3+ cells/kg with >99.9 % purity of CD3 + CD45RO+ memory T-cells was transferred. Following the DLI, a prompt increase in CD3 + CD4+ and CD3 + CD8+ counts was observed with a subsequent clearance of viral infections. No acute or chronic GvHD was observed. CONCLUSIONS: Automated depletion of CD45RA+ naïve T-cells from unmobilized whole blood is a simple and rapid strategy to provide unmanipulated DLIs, with a potentially broad repertoire of pathogen specific memory T-cells. In the haploidentical setting, CD45RA+ depleted DLIs can be safely administered at low T-cell doses for efficient enhancement of viral immunity and limited risk of GvHD. We demonstrate the successful use of this approach following TCR-α/β-cell depleted HSCT for the treatment of SCID.",2016 Jan 15,"['Brodszki, Nicholas', 'Turkiewicz, Dominik', 'Toporski, Jacek', 'Truedsson, Lennart', 'Dykes, Josefina']",Orphanet J Rare Dis,,,True
0bf39c12d7c4576441079e2e758ec1eacfe015d1,PMC,Subcellular fractionation method to study endosomal trafficking of Kaposi’s sarcoma-associated herpesvirus,http://dx.doi.org/10.1186/s13578-015-0066-2,PMC4714431,26779333,CC BY,"BACKGROUND: Virus entry involves multiple steps and is a highly orchestrated process on which successful infection collectively depends. Entry processes are commonly analyzed by monitoring internalized virus particles via Western blotting, polymerase chain reaction, and imaging techniques that allow scientist to track the intracellular location of the pathogen. Such studies have provided abundant direct evidence on how viruses interact with receptor molecules on the cell surface, induce cell signaling at the point of initial contact with the cell to facilitate internalization, and exploit existing endocytic mechanisms of the cell for their ultimate infectious agenda. However, there is dearth of knowledge in regards to trafficking of a virus via endosomes. Herein, we describe an optimized laboratory procedure to isolate individual organelles during different stages of endocytosis by performing subcellular fractionation. This methodology is established using Kaposi’s sarcoma-associated herpesvirus (KSHV) infection of human foreskin fibroblast (HFF) cells as a model. With KSHV and other herpesviruses alike, envelope glycoproteins have been widely reported to physically engage target cell surface receptors, such as integrins, in interactions leading to entry and subsequent infection. RESULTS: Subcellular fractionation was used to isolate early and late endosomes (EEs and LEs) by performing a series of centrifugations steps. Specifically, a centrifugation step post-homogenization was utilized to obtain the post-nuclear supernatant containing intact intracellular organelles in suspension. Successive fractionation via sucrose density gradient centrifugation was performed to isolate specific organelles including EEs and LEs. Intracellular KSHV trafficking was directly traced in the isolated endosomal fractions. Additionally, the subcellular fractionation approach demonstrates a key role for integrins in the endosomal trafficking of KSHV. The results obtained from fractionation studies corroborated those obtained by traditional imaging studies. CONCLUSIONS: This study is the first of its kind to employ a sucrose flotation gradient assay to map intracellular KSHV trafficking in HFF cells. We are confident that such an approach will serve as a powerful tool to directly study intracellular trafficking of a virus, signaling events occurring on endosomal membranes, and dynamics of molecular events within endosomes that are crucial for uncoating and virus escape into the cytosol.",2016 Jan 15,"['Walker, Lia R.', 'Hussein, Hosni A. M.', 'Akula, Shaw M.']",Cell Biosci,,,True
4630378a0db8bae16b58ac19b512f9fffb0fc98f,PMC,Impact of Mated Female Nonproductive Days in Breeding Herd after Porcine Epidemic Diarrhea Virus Outbreak,http://dx.doi.org/10.1371/journal.pone.0147316,PMC4714882,26771383,CC BY,"Porcine epidemic diarrhea virus (PEDV) is an important pathogen that has a significant economic impact on the swine industry by imposing a high rate of mortality in suckling piglets. However, limited information on the productivity values of gilts and sows infected with PEDV is available. Here, we evaluate the productivity index in gilts and sows during the 1-year period before (19 January 2013 to 18 January 2014) and after (19 January 2014 to 18 January 2015) a PEDV outbreak from a 2000-sow breeding herd in Taiwan. The farrowing rate (FR), return rate (RR), total pigs born per litter (TB), pigs born alive per litter (BA), weaning pigs per litter (WPL), pre-weaning mortality, percentage of sows mated by 7 days after weaning, weaning to first service interval (WFSI), mated female nonproductive days (NPDs), replacement rate of sows and sow culling rate were compared using productive records. The FR (-9.6%), RR (+9.8%), TB (-1.6), BA (-1.1), WPL (-1.1), sows mated by 7 days after weaning (-6.9%), WFSI (+0.8 days), NPDs (+6.9 days) and sow culling rate (+7.2%) were significantly different between the 1-year pre-PEDV outbreak period and the post-PEDV outbreak period. Impacts of the PEDV infection on the reproductive performance were more severe in pregnant gilts than in sows. In conclusion, these findings indicate that the outbreak of PEDV caused an increase in the rate of NPDs in breeding herds.",2016 Jan 15,"['Lin, Jung-Da', 'Lin, Chuen-Fu', 'Chung, Wen-Bin', 'Chiou, Ming-Tang', 'Lin, Chao-Nan']",PLoS One,,,True
52babe7e5a33e5c40aab00ea9b3e0ff4a3dfa3ba,PMC,"Co-Circulation of Canine Coronavirus I and IIa/b with High Prevalence and Genetic Diversity in Heilongjiang Province, Northeast China",http://dx.doi.org/10.1371/journal.pone.0146975,PMC4714894,26771312,CC BY,"To trace the evolution of canine coronavirus (CCoV), 201 stool samples from diarrheic dogs in northeast China were subjected to reverse transcription-polymerase chain reactions (RT-PCRs) targeting the partial M and S genes of CCoV, followed by an epidemiological analysis. M gene RT-PCRs showed that 28.36% (57/201) of the samples were positive for CCoV; of the 57 positive samples, CCoV-I and CCoV-II accounted for 15.79% (9/57) and 84.21% (48/57), respectively. A sequence comparison of the partial M gene revealed nucleotide homologies of 88.4%–100% among the 57 CCoV strains, and 88.7%–96.2% identity between the 57 CCoV strains and the Chinese reference strain HF3. The CCoV-I and CCoV-II strains exhibited genetic diversity when compared with reference strains from China and other countries. The 57 CCoV strains exhibited high co-infection rates with canine kobuvirus (CaKV) (33.33%) and canine parvovirus-2 (CPV-2) (31.58%). The CCoV prevalence in diarrheic dogs differed significantly with immunization status, regions, seasons, and ages. Moreover, 28 S genes were amplified from the 57 CCoV-positive samples, including 26 CCoV-IIa strains, one CCoV-IIb strain, and one CCoV-I strain. A sequence comparison of the partial S gene revealed 86.3%–100% nucleotide identity among the 26 CCoV-IIa strains, and 89.6%–92.2% identity between the 26 CCoV-IIa strains and the Chinese reference strain V1. The 26 CCoV-IIa strains showed genetic diversity when compared with reference strains from China and other countries. Our data provide evidence that CCoV-I, CCoV-IIa, and CCoV-IIb strains co-circulate in the diarrhoetic dogs in northeast China, high co-infection rates with CaKV and CPV-2 were observed, and the CCoV-II strains exhibited high prevalence and genetic diversity.",2016 Jan 15,"['Wang, Xinyu', 'Li, Chunqiu', 'Guo, Donghua', 'Wang, Xinyu', 'Wei, Shan', 'Geng, Yufei', 'Wang, Enyu', 'Wang, Zhihui', 'Zhao, Xiwen', 'Su, Mingjun', 'Liu, Qiujin', 'Zhang, Siyao', 'Feng, Li', 'Sun, Dongbo']",PLoS One,,,True
8dd14ffdb898c891d284cff71623b3e43ec0b0fe,PMC,Absence of Middle East respiratory syndrome coronavirus in Bactrian camels in the West Inner Mongolia Autonomous Region of China: surveillance study results from July 2015,http://dx.doi.org/10.1038/emi.2015.73,PMC4715163,26632875,CC BY,,2015 Dec 2,"['Liu, Renqiang', 'Wen, Zhiyuan', 'Wang, Jinling', 'Ge, Jinying', 'Chen, Hualan', 'Bu, Zhigao']",Emerg Microbes Infect,,,True
3373c12fcd9f891217dec7833378f696637b6ddd,PMC,Fragments of Target Cells are Internalized into Retroviral Envelope Protein-Expressing Cells during Cell-Cell Fusion by Endocytosis,http://dx.doi.org/10.3389/fmicb.2015.01552,PMC4717186,26834711,CC BY,"Retroviruses enter into host cells by fusion between viral and host cell membranes. Retroviral envelope glycoprotein (Env) induces the membrane fusion, and also mediates cell-cell fusion. There are two types of cell-cell fusions induced by the Env protein. Fusion-from-within is induced by fusion between viral fusogenic Env protein-expressing cells and susceptible cells, and virions induce fusion-from-without by fusion between adjacent cells. Although entry of ecotropic murine leukemia virus (E-MLV) requires host cell endocytosis, the involvement of endocytosis in cell fusion is unclear. By fluorescent microscopic analysis of the fusion-from-within, we found that fragments of target cells are internalized into Env-expressing cells. Treatment of the Env-expressing cells with an endocytosis inhibitor more significantly inhibited the cell fusion than that of the target cells, indicating that endocytosis in Env-expressing cells is required for the cell fusion. The endocytosis inhibitor also attenuated the fusion-from-without. Electron microscopic analysis suggested that the membrane fusion resulting in fusion-from-within initiates in endocytic membrane dents. This study shows that two types of the viral cell fusion both require endocytosis, and provides the cascade of fusion-from-within.",2016 Jan 19,"['Izumida, Mai', 'Kamiyama, Haruka', 'Suematsu, Takashi', 'Honda, Eri', 'Koizumi, Yosuke', 'Yasui, Kiyoshi', 'Hayashi, Hideki', 'Ariyoshi, Koya', 'Kubo, Yoshinao']",Front Microbiol,,,True
b33f78304f8fdb97631ad4b5b5ed9d8d85d0622f,PMC,Endogenous adaptation to low oxygen modulates T-cell regulatory pathways in EAE,http://dx.doi.org/10.1186/s12974-015-0407-4,PMC4717549,26785841,CC BY,"BACKGROUND: In the brain, chronic inflammatory activity may lead to compromised delivery of oxygen and glucose suggesting that therapeutic approaches aimed at restoring metabolic balance may be useful. In vivo exposure to chronic mild normobaric hypoxia (10 % oxygen) leads to a number of endogenous adaptations that includes vascular remodeling (angioplasticity). Angioplasticity promotes tissue survival. We have previously shown that induction of adaptive angioplasticity modulates the disease pattern in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). In the present study, we define mechanisms by which adaptation to low oxygen functionally ameliorates the signs and symptoms of EAE and for the first time show that tissue hypoxia may fundamentally alter neurodegenerative disease. METHODS: C57BL/6 mice were immunized with MOG, and some of them were kept in the hypoxia chambers (day 0) and exposed to 10 % oxygen for 3 weeks, while the others were kept at normoxic environment. Sham-immunized controls were included in both hypoxic and normoxic groups. Animals were sacrificed at pre-clinical and peak disease periods for tissue collection and analysis. RESULTS: Exposure to mild hypoxia decreased histological evidence of inflammation. Decreased numbers of cluster of differentiation (CD)4+ T cells were found in the hypoxic spinal cords associated with a delayed Th17-specific cytokine response. Hypoxia-induced changes did not alter the sensitization of peripheral T cells to the MOG peptide. Exposure to mild hypoxia induced significant increases in anti-inflammatory IL-10 levels and an increase in the number of spinal cord CD25+FoxP3+ T-regulatory cells. CONCLUSIONS: Acclimatization to mild hypoxia incites a number of endogenous adaptations that induces an anti-inflammatory milieu. Further understanding of these mechanisms system may pinpoint possible new therapeutic targets to treat neurodegenerative disease.",2016 Jan 19,"['Esen, Nilufer', 'Katyshev, Vladimir', 'Serkin, Zakhar', 'Katysheva, Svetlana', 'Dore-Duffy, Paula']",J Neuroinflammation,,,True
faa8c6b399eff710bae62ce297e56c19fe212e74,PMC,Advancement and applications of peptide phage display technology in biomedical science,http://dx.doi.org/10.1186/s12929-016-0223-x,PMC4717660,26786672,CC BY,"Combinatorial phage library is a powerful research tool for high-throughput screening of protein interactions. Of all available molecular display techniques, phage display has proven to be the most popular approach. Screening phage-displayed random peptide libraries is an effective means of identifying peptides that can bind target molecules and regulate their function. Phage-displayed peptide libraries can be used for (i) B-cell and T-cell epitope mapping, (ii) selection of bioactive peptides bound to receptors or proteins, disease-specific antigen mimics, peptides bound to non-protein targets, cell-specific peptides, or organ-specific peptides, and (iii) development of peptide-mediated drug delivery systems and other applications. Targeting peptides identified using phage display technology may be useful for basic research and translational medicine. In this review article, we summarize the latest technological advancements in the application of phage-displayed peptide libraries to applied biomedical sciences.",2016 Jan 19,"['Wu, Chien-Hsun', 'Liu, I-Ju', 'Lu, Ruei-Min', 'Wu, Han-Chung']",J Biomed Sci,,,True
5483fa35c312dcdefe0216e85fcbdafec45cf84e,PMC,Evolution of research in health geographics through the International Journal of Health Geographics (2002–2015),http://dx.doi.org/10.1186/s12942-016-0032-1,PMC4719657,26790403,CC BY,"Health geographics is a fast-developing research area. Subjects broached in scientific literature are most varied, ranging from vectorial diseases to access to healthcare, with a recent revival of themes such as the implication of health in the Smart City, or a predominantly individual-centered approach. Far beyond standard meta-analyses, the present study deliberately adopts the standpoint of questioning space in its foundations, through various authors of the International Journal of Health Geographics, a highly influential journal in that field. The idea is to find space as the common denominator in this specialized literature, as well as its relation to spatial analysis, without for all that trying to tend towards exhaustive approaches. 660 articles have being published in the journal since launch, but 359 articles were selected based on the presence of the word “Space” in either the title, or the abstract or the text over 13 years of the journal’s existence. From that database, a lexical analysis (tag cloud) reveals the perception of space in literature, and shows how approaches are evolving, thus underlining that the scope of health geographics is far from narrowing.",2016 Jan 20,"['Pérez, Sandra', 'Laperrière, Vincent', 'Borderon, Marion', 'Padilla, Cindy', 'Maignant, Gilles', 'Oliveau, Sébastien']",Int J Health Geogr,,,True
efd27ff0ac04dd60838266386aaebb5df80f4fa9,PMC,Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus,http://dx.doi.org/10.1371/journal.pone.0147041,PMC4720120,26761647,CC BY,"In order to improve clinical management and prevention of viral infections in hospitalised children improved etiological insight is needed. The aim of the present study was to assess the spectrum of respiratory viral pathogens in children admitted to hospital with acute respiratory tract infections in Cyprus. For this purpose nasopharyngeal swab samples from 424 children less than 12 years of age with acute respiratory tract infections were collected over three epidemic seasons and were analysed for the presence of the most common 15 respiratory viruses. A viral pathogen was identified in 86% of the samples, with multiple infections being observed in almost 20% of the samples. The most frequently detected viruses were RSV (30.4%) and Rhinovirus (27.4%). RSV exhibited a clear seasonality with marked peaks in January/February, while rhinovirus infections did not exhibit a pronounced seasonality being detected almost throughout the year. While RSV and PIV3 incidence decreased significantly with age, the opposite was observed for influenza A and B as well as adenovirus infections. The data presented expand our understanding of the epidemiology of viral respiratory tract infections in Cypriot children and will be helpful to the clinicians and researchers interested in the treatment and control of viral respiratory tract infections.",2016 Jan 13,"['Richter, Jan', 'Panayiotou, Christakis', 'Tryfonos, Christina', 'Koptides, Dana', 'Koliou, Maria', 'Kalogirou, Nikolas', 'Georgiou, Eleni', 'Christodoulou, Christina']",PLoS One,,,True
1acdf5e9f35557c6fc3c102e865354a6b2359bc3,PMC,Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus,http://dx.doi.org/10.1371/journal.pone.0147041,PMC4720120,26761647,CC BY,"In order to improve clinical management and prevention of viral infections in hospitalised children improved etiological insight is needed. The aim of the present study was to assess the spectrum of respiratory viral pathogens in children admitted to hospital with acute respiratory tract infections in Cyprus. For this purpose nasopharyngeal swab samples from 424 children less than 12 years of age with acute respiratory tract infections were collected over three epidemic seasons and were analysed for the presence of the most common 15 respiratory viruses. A viral pathogen was identified in 86% of the samples, with multiple infections being observed in almost 20% of the samples. The most frequently detected viruses were RSV (30.4%) and Rhinovirus (27.4%). RSV exhibited a clear seasonality with marked peaks in January/February, while rhinovirus infections did not exhibit a pronounced seasonality being detected almost throughout the year. While RSV and PIV3 incidence decreased significantly with age, the opposite was observed for influenza A and B as well as adenovirus infections. The data presented expand our understanding of the epidemiology of viral respiratory tract infections in Cypriot children and will be helpful to the clinicians and researchers interested in the treatment and control of viral respiratory tract infections.",2016 Jan 13,"['Richter, Jan', 'Panayiotou, Christakis', 'Tryfonos, Christina', 'Koptides, Dana', 'Koliou, Maria', 'Kalogirou, Nikolas', 'Georgiou, Eleni', 'Christodoulou, Christina']",PLoS One,,,False
7a5a7445e0af990d098dbad733a408edc32642ae,PMC,Middle East Respiratory Syndrome Coronavirus Intra-Host Populations Are Characterized by Numerous High Frequency Variants,http://dx.doi.org/10.1371/journal.pone.0146251,PMC4720378,26790002,CC0,"Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging human pathogen related to SARS virus. In vitro studies indicate this virus may have a broad host range suggesting an increased pandemic potential. Genetic and epidemiological evidence indicate camels serve as a reservoir for MERS virus but the mechanism of cross species transmission is unclear and many questions remain regarding the susceptibility of humans to infection. Deep sequencing data was obtained from the nasal samples of three camels that had been experimentally infected with a human MERS-CoV isolate. A majority of the genome was covered and average coverage was greater than 12,000x depth. Although only 5 mutations were detected in the consensus sequences, 473 intrahost single nucleotide variants were identified. Many of these variants were present at high frequencies and could potentially influence viral phenotype and the sensitivity of detection assays that target these regions for primer or probe binding.",2016 Jan 20,"['Borucki, Monica K.', 'Lao, Victoria', 'Hwang, Mona', 'Gardner, Shea', 'Adney, Danielle', 'Munster, Vincent', 'Bowen, Richard', 'Allen, Jonathan E.']",PLoS One,,,True
91af77e42a7599eda8f4d061e0261dc39b092df6,PMC,Middle East Respiratory Syndrome Coronavirus Intra-Host Populations Are Characterized by Numerous High Frequency Variants,http://dx.doi.org/10.1371/journal.pone.0146251,PMC4720378,26790002,CC0,"Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging human pathogen related to SARS virus. In vitro studies indicate this virus may have a broad host range suggesting an increased pandemic potential. Genetic and epidemiological evidence indicate camels serve as a reservoir for MERS virus but the mechanism of cross species transmission is unclear and many questions remain regarding the susceptibility of humans to infection. Deep sequencing data was obtained from the nasal samples of three camels that had been experimentally infected with a human MERS-CoV isolate. A majority of the genome was covered and average coverage was greater than 12,000x depth. Although only 5 mutations were detected in the consensus sequences, 473 intrahost single nucleotide variants were identified. Many of these variants were present at high frequencies and could potentially influence viral phenotype and the sensitivity of detection assays that target these regions for primer or probe binding.",2016 Jan 20,"['Borucki, Monica K.', 'Lao, Victoria', 'Hwang, Mona', 'Gardner, Shea', 'Adney, Danielle', 'Munster, Vincent', 'Bowen, Richard', 'Allen, Jonathan E.']",PLoS One,,,False
9acdb5b67128d1cf69d690e4a340f2c961ce778d,PMC,Middle East Respiratory Syndrome Coronavirus Intra-Host Populations Are Characterized by Numerous High Frequency Variants,http://dx.doi.org/10.1371/journal.pone.0146251,PMC4720378,26790002,CC0,"Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging human pathogen related to SARS virus. In vitro studies indicate this virus may have a broad host range suggesting an increased pandemic potential. Genetic and epidemiological evidence indicate camels serve as a reservoir for MERS virus but the mechanism of cross species transmission is unclear and many questions remain regarding the susceptibility of humans to infection. Deep sequencing data was obtained from the nasal samples of three camels that had been experimentally infected with a human MERS-CoV isolate. A majority of the genome was covered and average coverage was greater than 12,000x depth. Although only 5 mutations were detected in the consensus sequences, 473 intrahost single nucleotide variants were identified. Many of these variants were present at high frequencies and could potentially influence viral phenotype and the sensitivity of detection assays that target these regions for primer or probe binding.",2016 Jan 20,"['Borucki, Monica K.', 'Lao, Victoria', 'Hwang, Mona', 'Gardner, Shea', 'Adney, Danielle', 'Munster, Vincent', 'Bowen, Richard', 'Allen, Jonathan E.']",PLoS One,,,False
2bd4bc16d5673b6c0de2e4283abd461b43e45a64,PMC,Middle East Respiratory Syndrome Coronavirus Intra-Host Populations Are Characterized by Numerous High Frequency Variants,http://dx.doi.org/10.1371/journal.pone.0146251,PMC4720378,26790002,CC0,"Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging human pathogen related to SARS virus. In vitro studies indicate this virus may have a broad host range suggesting an increased pandemic potential. Genetic and epidemiological evidence indicate camels serve as a reservoir for MERS virus but the mechanism of cross species transmission is unclear and many questions remain regarding the susceptibility of humans to infection. Deep sequencing data was obtained from the nasal samples of three camels that had been experimentally infected with a human MERS-CoV isolate. A majority of the genome was covered and average coverage was greater than 12,000x depth. Although only 5 mutations were detected in the consensus sequences, 473 intrahost single nucleotide variants were identified. Many of these variants were present at high frequencies and could potentially influence viral phenotype and the sensitivity of detection assays that target these regions for primer or probe binding.",2016 Jan 20,"['Borucki, Monica K.', 'Lao, Victoria', 'Hwang, Mona', 'Gardner, Shea', 'Adney, Danielle', 'Munster, Vincent', 'Bowen, Richard', 'Allen, Jonathan E.']",PLoS One,,,False
eb6e2ba036db0dcd7515f6c8b74938e89201b8ab,PMC,Nucleoprotein of influenza A virus negatively impacts antiapoptotic protein API5 to enhance E2F1-dependent apoptosis and virus replication,http://dx.doi.org/10.1038/cddis.2015.360,PMC4720893,26673663,CC BY,"Apoptosis of host cells profoundly influences virus propagation and dissemination, events that are integral to influenza A virus (IAV) pathogenesis. The trigger for activation of apoptosis is regulated by an intricate interplay between cellular and viral proteins, with a strong bearing on IAV replication. Though the knowledge of viral proteins and mechanisms employed by IAV to induce apoptosis has advanced considerably of late, we know relatively little about the repertoire of host factors targeted by viral proteins. Thus, identification of cellular proteins that are hijacked by the virus will help us not only to understand the molecular underpinnings of IAV-induced apoptosis, but also to design future antiviral therapies. Here we show that the nucleoprotein (NP) of IAV directly interacts with and suppresses the expression of API5, a host antiapoptotic protein that antagonizes E2F1-dependent apoptosis. siRNA-mediated depletion of API5, in NP-overexpressed as well as IAV-infected cells, leads to upregulation of apoptotic protease activating factor 1 (APAF1), a downstream modulator of E2F1-mediated apoptosis, and cleavage of caspases 9 and 3, although a reciprocal pattern of these events was observed on ectopic overexpression of API5. In concordance with these observations, annexin V and 7AAD staining assays exhibit downregulation of early and late apoptosis in IAV-infected or NP-transfected cells on overexpression of API5. Most significantly, while overexpression of API5 decreases viral titers, cellular NP protein as well as mRNA levels in IAV-infected A549 cells, silencing of API5 expression causes a steep rise in the same parameters. From the data reported in this manuscript, we propose a proapoptotic role for NP in IAV pathogenesis, whereby it suppresses expression of antiapoptotic factor API5, thus potentiating the E2F1-dependent apoptotic pathway and ensuring viral replication.",2015 Dec 17,"['Mayank, A K', 'Sharma, S', 'Nailwal, H', 'Lal, S K']",Cell Death Dis,,,True
f1d92c740ecb6d711507ed6e483472c8e1ecb3a6,PMC,One health – an ecological and evolutionary framework for tackling Neglected Zoonotic Diseases,http://dx.doi.org/10.1111/eva.12341,PMC4721077,26834828,CC BY,"Understanding the complex population biology and transmission ecology of multihost parasites has been declared as one of the major challenges of biomedical sciences for the 21st century and the Neglected Zoonotic Diseases (NZDs) are perhaps the most neglected of all the Neglected Tropical Diseases (NTDs). Here we consider how multihost parasite transmission and evolutionary dynamics may affect the success of human and animal disease control programmes, particularly neglected diseases of the developing world. We review the different types of zoonotic interactions that occur, both ecological and evolutionary, their potential relevance for current human control activities, and make suggestions for the development of an empirical evidence base and theoretical framework to better understand and predict the outcome of such interactions. In particular, we consider whether preventive chemotherapy, the current mainstay of NTD control, can be successful without a One Health approach. Transmission within and between animal reservoirs and humans can have important ecological and evolutionary consequences, driving the evolution and establishment of drug resistance, as well as providing selective pressures for spill‐over, host switching, hybridizations and introgressions between animal and human parasites. Our aim here is to highlight the importance of both elucidating disease ecology, including identifying key hosts and tailoring control effort accordingly, and understanding parasite evolution, such as precisely how infectious agents may respond and adapt to anthropogenic change. Both elements are essential if we are to alleviate disease risks from NZDs in humans, domestic animals and wildlife.",2016 Jan 8,"['Webster, Joanne P.', 'Gower, Charlotte M.', 'Knowles, Sarah C. L.', 'Molyneux, David H.', 'Fenton, Andy']",Evol Appl,,,True
4a074382e2fd63f0f5e882c0014e1e07d61c286a,PMC,Recent advances in biosynthesis of bioactive compounds in traditional Chinese medicinal plants,http://dx.doi.org/10.1007/s11434-015-0929-2,PMC4722072,26844006,CC BY,"Plants synthesize and accumulate large amount of specialized (or secondary) metabolites also known as natural products, which provide a rich source for modern pharmacy. In China, plants have been used in traditional medicine for thousands of years. Recent development of molecular biology, genomics and functional genomics as well as high-throughput analytical chemical technologies has greatly promoted the research on medicinal plants. In this article, we review recent advances in the elucidation of biosynthesis of specialized metabolites in medicinal plants, including phenylpropanoids, terpenoids and alkaloids. These natural products may share a common upstream pathway to form a limited numbers of common precursors, but are characteristic in distinct modifications leading to highly variable structures. Although this review is focused on traditional Chinese medicine, other plants with a great medicinal interest or potential are also discussed. Understanding of their biosynthesis processes is critical for producing these highly value molecules at large scale and low cost in microbes and will benefit to not only human health but also plant resource conservation.",2016 Nov 2,"['Yang, Lei', 'Yang, Changqing', 'Li, Chenyi', 'Zhao, Qing', 'Liu, Ling', 'Fang, Xin', 'Chen, Xiao-Ya']",Sci Bull (Beijing),,,True
3ed1483725e4ea6abcdbf93585eeccde903202fd,PMC,The first case of the 2015 Korean Middle East Respiratory Syndrome outbreak,http://dx.doi.org/10.4178/epih/e2015049,PMC4722220,26725226,CC BY,"This study reviewed problems in the prevention of outbreak and spread of Middle East Respiratory Syndrome (MERS) and aimed to provide assistance in establishing policies to prevent and manage future outbreaks of novel infectious diseases of foreign origin via in-depth epidemiological investigation of the patient who initiated the MERS outbreak in Korea, 2015. Personal and phone interviews were conducted with the patient and his guardians, and his activities in Saudi Arabia were investigated with the help of the Saudi Arabian Ministry of Health. Clinical courses and test results were confirmed from the medical records. The patient visited 4 medical facilities and contacted 742 people between May 11, 2015, at symptom onset, and May 20, at admission to the National Medical Center; 28 people were infected and diagnosed with MERS thereafter. Valuable lessons learned included: (1) epidemiological knowledge on the MERS transmission pattern and medical knowledge on its clinical course; (2) improvement of epidemiological investigative methods via closed-circuit television, global positioning system tracking, and review of Health Insurance Review and Assessment Service records; (3) problems revealed in the existing preventive techniques, including early determination of the various people contacted; (4) experiences with preventive methods used for the first time in Korea, including cohort quarantine; (5) reconsideration of the management systems for infectious disease outbreaks across the country, such as this case, at the levels of central government, local government, and the public; (6) reconsideration of hospital infectious disease management systems, culture involving patient visitation, and emergency room environments.",2015 Nov 14,"['Park, Yong-Shik', 'Lee, Changhwan', 'Kim, Kyung Min', 'Kim, Seung Woo', 'Lee, Keon-Joo', 'Ahn, Jungmo', 'Ki, Moran']",Epidemiol Health,,,True
5d96b673ebcceaca3fbfedc78675fed62c2bf8d9,PMC,The first case of the 2015 Korean Middle East Respiratory Syndrome outbreak,http://dx.doi.org/10.4178/epih/e2015049,PMC4722220,26725226,CC BY,"This study reviewed problems in the prevention of outbreak and spread of Middle East Respiratory Syndrome (MERS) and aimed to provide assistance in establishing policies to prevent and manage future outbreaks of novel infectious diseases of foreign origin via in-depth epidemiological investigation of the patient who initiated the MERS outbreak in Korea, 2015. Personal and phone interviews were conducted with the patient and his guardians, and his activities in Saudi Arabia were investigated with the help of the Saudi Arabian Ministry of Health. Clinical courses and test results were confirmed from the medical records. The patient visited 4 medical facilities and contacted 742 people between May 11, 2015, at symptom onset, and May 20, at admission to the National Medical Center; 28 people were infected and diagnosed with MERS thereafter. Valuable lessons learned included: (1) epidemiological knowledge on the MERS transmission pattern and medical knowledge on its clinical course; (2) improvement of epidemiological investigative methods via closed-circuit television, global positioning system tracking, and review of Health Insurance Review and Assessment Service records; (3) problems revealed in the existing preventive techniques, including early determination of the various people contacted; (4) experiences with preventive methods used for the first time in Korea, including cohort quarantine; (5) reconsideration of the management systems for infectious disease outbreaks across the country, such as this case, at the levels of central government, local government, and the public; (6) reconsideration of hospital infectious disease management systems, culture involving patient visitation, and emergency room environments.",2015 Nov 14,"['Park, Yong-Shik', 'Lee, Changhwan', 'Kim, Kyung Min', 'Kim, Seung Woo', 'Lee, Keon-Joo', 'Ahn, Jungmo', 'Ki, Moran']",Epidemiol Health,,,False
da44bf992234002dde4e9301581944911e58a633,PMC,"Lessons learned from new emerging infectious disease, Middle East Respiratory Syndrome coronavirus outbreak in Korea",http://dx.doi.org/10.4178/epih/e2015051,PMC4722224,26725227,CC BY,,2015 Nov 17,"Kim, Joung Soon",Epidemiol Health,,,False
293bebb82f2e4687a1d257e75483a2e150de41b1,PMC,"Lessons learned from new emerging infectious disease, Middle East Respiratory Syndrome coronavirus outbreak in Korea",http://dx.doi.org/10.4178/epih/e2015051,PMC4722224,26725227,CC BY,,2015 Nov 17,"Kim, Joung Soon",Epidemiol Health,,,False
634b79269e0f00d35bcea1a2dc7643884b8c6b3a,PMC,Surface vimentin is critical for the cell entry of SARS-CoV,http://dx.doi.org/10.1186/s12929-016-0234-7,PMC4724099,26801988,CC BY,"BACKGROUND: Severe acute respiratory syndrome coronavirus (SARS-CoV) caused a global panic due to its high morbidity and mortality during 2002 and 2003. Soon after the deadly disease outbreak, the angiotensin-converting enzyme 2 (ACE2) was identified as a functional cellular receptor in vitro and in vivo for SARS-CoV spike protein. However, ACE2 solely is not sufficient to allow host cells to become susceptible to SARS-CoV infection, and other host factors may be involved in SARS-CoV spike protein-ACE2 complex. RESULTS: A host intracellular filamentous cytoskeletal protein vimentin was identified by immunoprecipitation and LC-MS/MS analysis following chemical cross-linking on Vero E6 cells that were pre-incubated with the SARS-CoV spike protein. Moreover, flow cytometry data demonstrated an increase of the cell surface vimentin level by 16.5 % after SARS-CoV permissive Vero E6 cells were treated with SARS-CoV virus-like particles (VLPs). A direct interaction between SARS-CoV spike protein and host surface vimentin was further confirmed by far-Western blotting. In addition, antibody neutralization assay and shRNA knockdown experiments indicated a vital role of vimentin in cell binding and uptake of SARS-CoV VLPs and the viral spike protein. CONCLUSIONS: A direct interaction between vimentin and SARS-CoV spike protein during viral entry was observed. Vimentin is a putative anti-viral drug target for preventing/reducing the susceptibility to SARS-CoV infection.",2016 Jan 22,"['Yu, Yvonne Ting-Chun', 'Chien, Ssu-Chia', 'Chen, I-Yin', 'Lai, Chia-Tsen', 'Tsay, Yeou-Guang', 'Chang, Shin C.', 'Chang, Ming-Fu']",J Biomed Sci,,,True
4878d966944fb0b66d96fec7b7dff3f79194f26d,PMC,Endocytic function is critical for influenza A virus infection via DC-SIGN and L-SIGN,http://dx.doi.org/10.1038/srep19428,PMC4725901,26763587,CC BY,"The ubiquitous presence of cell-surface sialic acid (SIA) has complicated efforts to identify specific transmembrane glycoproteins that function as bone fide entry receptors for influenza A virus (IAV) infection. The C-type lectin receptors (CLRs) DC-SIGN (CD209) and L-SIGN (CD209L) enhance IAV infection however it is not known if they act as attachment factors, passing virions to other unknown receptors for virus entry, or as authentic entry receptors for CLR-mediated virus uptake and infection. Sialic acid-deficient Lec2 Chinese Hamster Ovary (CHO) cell lines were resistant to IAV infection whereas expression of DC-SIGN/L-SIGN restored susceptibility of Lec2 cells to pH- and dynamin-dependent infection. Moreover, Lec2 cells expressing endocytosis-defective DC-SIGN/L-SIGN retained capacity to bind IAV but showed reduced susceptibility to infection. These studies confirm that DC-SIGN and L-SIGN are authentic endocytic receptors for IAV entry and infection.",2016 Jan 14,"['Gillespie, Leah', 'Roosendahl, Paula', 'Ng, Wy Ching', 'Brooks, Andrew G.', 'Reading, Patrick C.', 'Londrigan, Sarah L.']",Sci Rep,,,True
abb5a68caf42d65dcb946056258028cccf87cd4a,PMC,A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus,http://dx.doi.org/10.1038/srep19176,PMC4726036,26777545,CC BY,"Virus evolves rapidly to escape vaccine-induced immunity, posing a desperate demand for efficient vaccine development biotechnologies. Here we present an express vaccine development strategy based on CRISPR/Cas9 and Cre/Lox system against re-emerging Pseudorabies virus, which caused the recent devastating swine pseudorabies outbreak in China. By CRISPR/Cas9 system, the virulent genes of the newly isolated strain were simultaneously substituted by marker genes, which were subsequently excised using Cre/Lox system for vaccine safety concern. Notably, single cell FACS technology was applied to further promote virus purification efficiency. The combination of these state-of-art technologies greatly accelerated vaccine development. Finally, vaccination and challenge experiments proved this vaccine candidate’s protective efficacy in pigs and the promise to control current pseudorabies outbreak. This is, to our knowledge, the first successful vaccine development based on gene edit technologies, demonstrating these technologies leap from laboratory to industry. It may pave the way for future express antiviral vaccine development.",2016 Jan 18,"['Liang, Xun', 'Sun, Leqiang', 'Yu, Teng', 'Pan, Yongfei', 'Wang, Dongdong', 'Hu, Xueying', 'Fu, Zhenfang', 'He, Qigai', 'Cao, Gang']",Sci Rep,,,True
3240a95510e3a28cf3215c72090000c3458ca8db,PMC,A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus,http://dx.doi.org/10.1038/srep19176,PMC4726036,26777545,CC BY,"Virus evolves rapidly to escape vaccine-induced immunity, posing a desperate demand for efficient vaccine development biotechnologies. Here we present an express vaccine development strategy based on CRISPR/Cas9 and Cre/Lox system against re-emerging Pseudorabies virus, which caused the recent devastating swine pseudorabies outbreak in China. By CRISPR/Cas9 system, the virulent genes of the newly isolated strain were simultaneously substituted by marker genes, which were subsequently excised using Cre/Lox system for vaccine safety concern. Notably, single cell FACS technology was applied to further promote virus purification efficiency. The combination of these state-of-art technologies greatly accelerated vaccine development. Finally, vaccination and challenge experiments proved this vaccine candidate’s protective efficacy in pigs and the promise to control current pseudorabies outbreak. This is, to our knowledge, the first successful vaccine development based on gene edit technologies, demonstrating these technologies leap from laboratory to industry. It may pave the way for future express antiviral vaccine development.",2016 Jan 18,"['Liang, Xun', 'Sun, Leqiang', 'Yu, Teng', 'Pan, Yongfei', 'Wang, Dongdong', 'Hu, Xueying', 'Fu, Zhenfang', 'He, Qigai', 'Cao, Gang']",Sci Rep,,,False
55248fb2e12f9712b35a26e3fdb723baea0ac775,PMC,Genomic Motifs as a Novel Indicator of the Relationship between Strains Isolated from the Epidemic of Porcine Epidemic Diarrhea in 2013-2014,http://dx.doi.org/10.1371/journal.pone.0147994,PMC4726493,26808527,CC BY,"Porcine epidemic diarrhea virus (PEDV) is a positive-sense RNA virus that causes infectious gastroenteritis in pigs. Following a PED outbreak that occurred in China in 2010, the disease was identified for the first time in the United States in April 2013, and was reported in many other countries worldwide from 2013 to 2014. As a novel approach to elucidate the epidemiological relationship between PEDV strains, we explored their genome sequences to identify the motifs that were shared within related strains. Of PED outbreaks reported in many countries during 2013–2014, 119 PEDV strains in Japan, USA, Canada, Mexico, Germany, and Korea were selected and used in this study. We developed a motif mining program, which aimed to identify a specific region of the genome that was exclusively shared by a group of PEDV strains. Eight motifs were identified (M1–M8) and they were observed in 41, 9, 18, 6, 10, 14, 2, and 2 strains, respectively. Motifs M1–M6 were shared by strains from more than two countries, and seemed to originate from one PEDV strain, Indiana12.83/USA/2013, among the 119 strains studied. BLAST search for motifs M1–M6 revealed that M3–M5 were almost identical to the strain ZMDZY identified in 2011 in China, while M1 and M2 were similar to other Chinese strains isolated in 2011–2012. Consequently, the PED outbreaks in these six countries may be closely related, and multiple transmissions of PEDV strains between these countries may have occurred during 2013–2014. Although tools such as phylogenetic tree analysis with whole genome sequences are increasingly applied to reveal the connection between isolates, its interpretation is sometimes inconclusive. Application of motifs as a tool to examine the whole genome sequences of causative agents will be more objective and will be an explicit indicator of their relationship.",2016 Jan 25,"['Yamamoto, Takehisa', 'Suzuki, Tohru', 'Ohashi, Seiichi', 'Miyazaki, Ayako', 'Tsutsui, Toshiyuki']",PLoS One,,,True
17d4c1e70195453379ed6529851c51d204fdc926,PMC,Bovine respiratory syncytial virus outbreak reduced bulls’ weight gain and feed conversion for eight months in a Norwegian beef herd,http://dx.doi.org/10.1186/s13028-016-0190-y,PMC4727385,26810215,CC BY,"BACKGROUND: Cost-benefit evaluation of measures against respiratory disease in cattle requires accounting with the associated production losses. Investigations of naturally occurring respiratory infections in a herd setting are an opportunity for accurate estimates of the consequences. This article presents estimates based on individual monitoring of weight and concentrate intake of several hundred bulls previous to, during and after a respiratory infection outbreak with bovine respiratory syncytial virus (BRSV) as the main pathogen. The aim of the study was to analyse the association between exposure to BRSV, weight gain and feed conversion rate, quantify any change in these parameters, and estimate the duration of the change in production. RESULTS: A comparison of growth curves for the bulls that were present during the outbreak revealed that bulls with severe clinical signs had a clear and consistent trend of poorer growth rate than those with milder or no signs. The weight/age-ratio was 0.04–0.10 lower in the severely affected bulls, and evident throughout the study period of 8 months. A comparison of growth rates between apparently healthy bulls being present during the outbreak and a comparable group of bulls exactly 1 year later (n = 377) showed a reduced growth rate of 111 g/day in the first group. The difference amounted to 23 extra days needed to reach the reference weight. Feed conversion was also reduced by 79 g weight gain/kilogram concentrate consumed in the outbreak year. CONCLUSION: This study indicates significant negative effects on performance of animals that develop severe clinical signs in the acute stage, and that the growth and production is negatively affected many months after apparent recovery. In addition, the performance of apparently healthy animals that are exposed during an outbreak are severely negatively affected. The duration of this decrease in production in animals after recovery, or animals that have not shown disease at all, has not previously been documented. These losses will easily be underestimated, but contribute significantly to the costs for the producer. The findings emphasize the importance of BRSV infection for profitability and animal welfare in cattle husbandry. The study also illustrates that utilising intra-herd comparison of health and production parameters is a productive approach to estimate consequences of an outbreak.",2016 Jan 25,"['Klem, Thea Blystad', 'Kjæstad, Hans Petter', 'Kummen, Eiliv', 'Holen, Hallstein', 'Stokstad, Maria']",Acta Vet Scand,,,True
39855ca915f908855de8577baf009e5b1acf5f5c,PMC,Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus,http://dx.doi.org/10.1038/srep19840,PMC4728398,26813885,CC BY,"Respiratory syncytial virus (RSV) infection is a major cause of severe lower respiratory illness in infants and young children, but the underlying mechanisms responsible for viral pathogenesis have not been fully elucidated. To date, no drugs or vaccines have been employed to improve clinical outcomes for RSV-infected patients. In this paper, we report that angiotensin-converting enzyme-2 (ACE2) protected against severe lung injury induced by RSV infection in an experimental mouse model and in pediatric patients. Moreover, ACE2 deficiency aggravated RSV-associated disease pathogenesis, mainly by its action on the angiotensin II type 1 receptor (AT1R). Furthermore, administration of a recombinant ACE2 protein alleviated the severity of RSV-induced lung injury. These findings demonstrate that ACE2 plays a critical role in preventing RSV-induced lung injury, and suggest that ACE2 is a promising potential therapeutic target in the management of RSV-induced lung disease.",2016 Jan 27,"['Gu, Hongjing', 'Xie, Zhengde', 'Li, Tieling', 'Zhang, Shaogeng', 'Lai, Chengcai', 'Zhu, Ping', 'Wang, Keyu', 'Han, Lina', 'Duan, Yueqiang', 'Zhao, Zhongpeng', 'Yang, Xiaolan', 'Xing, Li', 'Zhang, Peirui', 'Wang, Zhouhai', 'Li, Ruisheng', 'Yu, Jane J.', 'Wang, Xiliang', 'Yang, Penghui']",Sci Rep,,,True
63a98dbb196b0ceacae4a16715ca8540b857cd22,PMC,Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry,http://dx.doi.org/10.3390/v8010006,PMC4728566,26712783,CC BY,"Influenza A viruses (IAVs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-IAV agents. The glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. Here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including A/Puerto Rico/8/34 (H1N1), A/FM-1/47/1 (H1N1), and A/Aichi/2/68 (H3N2) with half maximal inhibitory concentration (IC(50)) of 7.756 ± 1.097, 6.225 ± 0.467, and 2.738 ± 1.931 μg/mL, respectively. Mechanism studies identified that quercetin showed interaction with the HA2 subunit. Moreover, quercetin could inhibit the entry of the H5N1 virus using the pseudovirus-based drug screening system. This study indicates that quercetin showing inhibitory activity in the early stage of influenza infection provides a future therapeutic option to develop effective, safe and affordable natural products for the treatment and prophylaxis of IAV infections.",2015 Dec 25,"['Wu, Wenjiao', 'Li, Richan', 'Li, Xianglian', 'He, Jian', 'Jiang, Shibo', 'Liu, Shuwen', 'Yang, Jie']",Viruses,,,True
df605c7743673dade86350172a3c6513bc437c90,PMC,Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC,http://dx.doi.org/10.3390/v8010016,PMC4728576,26761027,CC BY,"Rhinoviruses (RVs) and respiratory enteroviruses (EVs) are leading causes of upper respiratory tract infections and among the most frequent infectious agents in humans worldwide. Both are classified in the Enterovirus genus within the Picornaviridae family and they have been assigned to seven distinct species, RV-A, B, C and EV-A, B, C, D. As viral infections of public health significance, they represent an important financial burden on health systems worldwide. However, the lack of efficient antiviral treatment or vaccines against these highly prevalent pathogens prevents an effective management of RV-related diseases. Current advances in molecular diagnostic techniques have revealed the presence of RV in the lower respiratory tract and its role in lower airway diseases is increasingly reported. In addition to an established etiological role in the common cold, these viruses demonstrate an unexpected capacity to spread to other body sites under certain conditions. Some of these viruses have received particular attention recently, such as EV-D68 that caused a large outbreak of respiratory illness in 2014, respiratory EVs from species C, or viruses within the newly-discovered RV-C species. This review provides an update of the latest findings on clinical and fundamental aspects of RV and respiratory EV, including a summary of basic knowledge of their biology.",2016 Jan 11,"['Royston, Léna', 'Tapparel, Caroline']",Viruses,,,True
0181010a40e179c9b66d8b1f0eaac4fbf0ab6341,PMC,Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC,http://dx.doi.org/10.3390/v8010016,PMC4728576,26761027,CC BY,"Rhinoviruses (RVs) and respiratory enteroviruses (EVs) are leading causes of upper respiratory tract infections and among the most frequent infectious agents in humans worldwide. Both are classified in the Enterovirus genus within the Picornaviridae family and they have been assigned to seven distinct species, RV-A, B, C and EV-A, B, C, D. As viral infections of public health significance, they represent an important financial burden on health systems worldwide. However, the lack of efficient antiviral treatment or vaccines against these highly prevalent pathogens prevents an effective management of RV-related diseases. Current advances in molecular diagnostic techniques have revealed the presence of RV in the lower respiratory tract and its role in lower airway diseases is increasingly reported. In addition to an established etiological role in the common cold, these viruses demonstrate an unexpected capacity to spread to other body sites under certain conditions. Some of these viruses have received particular attention recently, such as EV-D68 that caused a large outbreak of respiratory illness in 2014, respiratory EVs from species C, or viruses within the newly-discovered RV-C species. This review provides an update of the latest findings on clinical and fundamental aspects of RV and respiratory EV, including a summary of basic knowledge of their biology.",2016 Jan 11,"['Royston, Léna', 'Tapparel, Caroline']",Viruses,,,True
52662ce54ce7eec49dce4d7c0592075227729f3e,PMC,Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments,http://dx.doi.org/10.3390/v8010023,PMC4728583,26797629,CC BY,"Since its emergence in the 1990s, White Spot Disease (WSD) has had major economic and societal impact in the crustacean aquaculture sector. Over the years shrimp farming alone has experienced billion dollar losses through WSD. The disease is caused by the White Spot Syndrome Virus (WSSV), a large dsDNA virus and the only member of the Nimaviridae family. Susceptibility to WSSV in a wide range of crustacean hosts makes it a major risk factor in the translocation of live animals and in commodity products. Currently there are no effective treatments for this disease. Understanding the molecular basis of disease processes has contributed significantly to the treatment of many human and animal pathogens, and with a similar aim considerable efforts have been directed towards understanding host–pathogen molecular interactions for WSD. Work on the molecular mechanisms of pathogenesis in aquatic crustaceans has been restricted by a lack of sequenced and annotated genomes for host species. Nevertheless, some of the key host–pathogen interactions have been established: between viral envelope proteins and host cell receptors at initiation of infection, involvement of various immune system pathways in response to WSSV, and the roles of various host and virus miRNAs in mitigation or progression of disease. Despite these advances, many fundamental knowledge gaps remain; for example, the roles of the majority of WSSV proteins are still unknown. In this review we assess current knowledge of how WSSV infects and replicates in its host, and critique strategies for WSD treatment.",2016 Jan 18,"['Verbruggen, Bas', 'Bickley, Lisa K.', 'van Aerle, Ronny', 'Bateman, Kelly S.', 'Stentiford, Grant D.', 'Santos, Eduarda M.', 'Tyler, Charles R.']",Viruses,,,True
5106124c0ccbe2da3746b20d396088112c6a420f,PMC,RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations,http://dx.doi.org/10.1186/s12864-016-2403-1,PMC4729133,26819139,CC BY,"BACKGROUND: Avian infectious bronchitis is a highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high (L10H line) and low (L10L line) serum concentration of mannose-binding lectin (MBL) were studied. In total, 32 birds from each line were used. Sixteen birds from each line were infected with IBV and sixteen were left uninfected. Eight uninfected and infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds and differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and in the same way for infected birds. Functional analysis was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. RESULTS: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” and “Somatic recombination of immunoglobulin genes involved in immune response” at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” and “Positive regulation of leukocyte activation” at weeks 1 and 3, respectively. CONCLUSIONS: Healthy birds from the two lines showed significant differences in expression profiles for subsets of adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had influenced innate as well as adaptive immunity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2403-1) contains supplementary material, which is available to authorized users.",2016 Jan 27,"['Hamzić, Edin', 'Kjærup, Rikke Brødsgaard', 'Mach, Núria', 'Minozzi, Guilietta', 'Strozzi, Francesco', 'Gualdi, Valentina', 'Williams, John L.', 'Chen, Jun', 'Wattrang, Eva', 'Buitenhuis, Bart', 'Juul-Madsen, Helle Risdahl', 'Dalgaard, Tina Sørensen']",BMC Genomics,,,False
70b4b035e92da4a05093847f3f31cfea47d673cc,PMC,RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations,http://dx.doi.org/10.1186/s12864-016-2403-1,PMC4729133,26819139,CC BY,"BACKGROUND: Avian infectious bronchitis is a highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high (L10H line) and low (L10L line) serum concentration of mannose-binding lectin (MBL) were studied. In total, 32 birds from each line were used. Sixteen birds from each line were infected with IBV and sixteen were left uninfected. Eight uninfected and infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds and differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and in the same way for infected birds. Functional analysis was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. RESULTS: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” and “Somatic recombination of immunoglobulin genes involved in immune response” at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” and “Positive regulation of leukocyte activation” at weeks 1 and 3, respectively. CONCLUSIONS: Healthy birds from the two lines showed significant differences in expression profiles for subsets of adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had influenced innate as well as adaptive immunity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2403-1) contains supplementary material, which is available to authorized users.",2016 Jan 27,"['Hamzić, Edin', 'Kjærup, Rikke Brødsgaard', 'Mach, Núria', 'Minozzi, Guilietta', 'Strozzi, Francesco', 'Gualdi, Valentina', 'Williams, John L.', 'Chen, Jun', 'Wattrang, Eva', 'Buitenhuis, Bart', 'Juul-Madsen, Helle Risdahl', 'Dalgaard, Tina Sørensen']",BMC Genomics,,,False
2cad52c0f90e80ad4794ba31bd99f06f211d5c2b,PMC,RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations,http://dx.doi.org/10.1186/s12864-016-2403-1,PMC4729133,26819139,CC BY,"BACKGROUND: Avian infectious bronchitis is a highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high (L10H line) and low (L10L line) serum concentration of mannose-binding lectin (MBL) were studied. In total, 32 birds from each line were used. Sixteen birds from each line were infected with IBV and sixteen were left uninfected. Eight uninfected and infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds and differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and in the same way for infected birds. Functional analysis was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. RESULTS: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” and “Somatic recombination of immunoglobulin genes involved in immune response” at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” and “Positive regulation of leukocyte activation” at weeks 1 and 3, respectively. CONCLUSIONS: Healthy birds from the two lines showed significant differences in expression profiles for subsets of adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had influenced innate as well as adaptive immunity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2403-1) contains supplementary material, which is available to authorized users.",2016 Jan 27,"['Hamzić, Edin', 'Kjærup, Rikke Brødsgaard', 'Mach, Núria', 'Minozzi, Guilietta', 'Strozzi, Francesco', 'Gualdi, Valentina', 'Williams, John L.', 'Chen, Jun', 'Wattrang, Eva', 'Buitenhuis, Bart', 'Juul-Madsen, Helle Risdahl', 'Dalgaard, Tina Sørensen']",BMC Genomics,,,False
5e9be7630693730ad6dfe2569448b33c03c12bdb,PMC,RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations,http://dx.doi.org/10.1186/s12864-016-2403-1,PMC4729133,26819139,CC BY,"BACKGROUND: Avian infectious bronchitis is a highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high (L10H line) and low (L10L line) serum concentration of mannose-binding lectin (MBL) were studied. In total, 32 birds from each line were used. Sixteen birds from each line were infected with IBV and sixteen were left uninfected. Eight uninfected and infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds and differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and in the same way for infected birds. Functional analysis was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. RESULTS: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” and “Somatic recombination of immunoglobulin genes involved in immune response” at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” and “Positive regulation of leukocyte activation” at weeks 1 and 3, respectively. CONCLUSIONS: Healthy birds from the two lines showed significant differences in expression profiles for subsets of adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had influenced innate as well as adaptive immunity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2403-1) contains supplementary material, which is available to authorized users.",2016 Jan 27,"['Hamzić, Edin', 'Kjærup, Rikke Brødsgaard', 'Mach, Núria', 'Minozzi, Guilietta', 'Strozzi, Francesco', 'Gualdi, Valentina', 'Williams, John L.', 'Chen, Jun', 'Wattrang, Eva', 'Buitenhuis, Bart', 'Juul-Madsen, Helle Risdahl', 'Dalgaard, Tina Sørensen']",BMC Genomics,,,False
1a96c7d91d342a55bcafadc1b639e2264a4daea9,PMC,RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations,http://dx.doi.org/10.1186/s12864-016-2403-1,PMC4729133,26819139,CC BY,"BACKGROUND: Avian infectious bronchitis is a highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high (L10H line) and low (L10L line) serum concentration of mannose-binding lectin (MBL) were studied. In total, 32 birds from each line were used. Sixteen birds from each line were infected with IBV and sixteen were left uninfected. Eight uninfected and infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds and differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and in the same way for infected birds. Functional analysis was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. RESULTS: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” and “Somatic recombination of immunoglobulin genes involved in immune response” at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” and “Positive regulation of leukocyte activation” at weeks 1 and 3, respectively. CONCLUSIONS: Healthy birds from the two lines showed significant differences in expression profiles for subsets of adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had influenced innate as well as adaptive immunity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2403-1) contains supplementary material, which is available to authorized users.",2016 Jan 27,"['Hamzić, Edin', 'Kjærup, Rikke Brødsgaard', 'Mach, Núria', 'Minozzi, Guilietta', 'Strozzi, Francesco', 'Gualdi, Valentina', 'Williams, John L.', 'Chen, Jun', 'Wattrang, Eva', 'Buitenhuis, Bart', 'Juul-Madsen, Helle Risdahl', 'Dalgaard, Tina Sørensen']",BMC Genomics,,,False
636512bc06a771a13d2ea72ce74f2ec2b37009c5,PMC,RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations,http://dx.doi.org/10.1186/s12864-016-2403-1,PMC4729133,26819139,CC BY,"BACKGROUND: Avian infectious bronchitis is a highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high (L10H line) and low (L10L line) serum concentration of mannose-binding lectin (MBL) were studied. In total, 32 birds from each line were used. Sixteen birds from each line were infected with IBV and sixteen were left uninfected. Eight uninfected and infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds and differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and in the same way for infected birds. Functional analysis was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. RESULTS: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” and “Somatic recombination of immunoglobulin genes involved in immune response” at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” and “Positive regulation of leukocyte activation” at weeks 1 and 3, respectively. CONCLUSIONS: Healthy birds from the two lines showed significant differences in expression profiles for subsets of adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had influenced innate as well as adaptive immunity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2403-1) contains supplementary material, which is available to authorized users.",2016 Jan 27,"['Hamzić, Edin', 'Kjærup, Rikke Brødsgaard', 'Mach, Núria', 'Minozzi, Guilietta', 'Strozzi, Francesco', 'Gualdi, Valentina', 'Williams, John L.', 'Chen, Jun', 'Wattrang, Eva', 'Buitenhuis, Bart', 'Juul-Madsen, Helle Risdahl', 'Dalgaard, Tina Sørensen']",BMC Genomics,,,False
f5f1cd43740b5b6eca8b3cf2714fc0854a746519,PMC,RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations,http://dx.doi.org/10.1186/s12864-016-2403-1,PMC4729133,26819139,CC BY,"BACKGROUND: Avian infectious bronchitis is a highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high (L10H line) and low (L10L line) serum concentration of mannose-binding lectin (MBL) were studied. In total, 32 birds from each line were used. Sixteen birds from each line were infected with IBV and sixteen were left uninfected. Eight uninfected and infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds and differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and in the same way for infected birds. Functional analysis was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. RESULTS: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” and “Somatic recombination of immunoglobulin genes involved in immune response” at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” and “Positive regulation of leukocyte activation” at weeks 1 and 3, respectively. CONCLUSIONS: Healthy birds from the two lines showed significant differences in expression profiles for subsets of adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had influenced innate as well as adaptive immunity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2403-1) contains supplementary material, which is available to authorized users.",2016 Jan 27,"['Hamzić, Edin', 'Kjærup, Rikke Brødsgaard', 'Mach, Núria', 'Minozzi, Guilietta', 'Strozzi, Francesco', 'Gualdi, Valentina', 'Williams, John L.', 'Chen, Jun', 'Wattrang, Eva', 'Buitenhuis, Bart', 'Juul-Madsen, Helle Risdahl', 'Dalgaard, Tina Sørensen']",BMC Genomics,,,True
9800de42f4f105fbd335179bef0fd6a57036d5ed,PMC,An Open Receptor-Binding Cavity of Hemagglutinin-Esterase-Fusion Glycoprotein from Newly-Identified Influenza D Virus: Basis for Its Broad Cell Tropism,http://dx.doi.org/10.1371/journal.ppat.1005411,PMC4729479,26816272,CC BY,"Influenza viruses cause seasonal flu each year and pandemics or epidemic sporadically, posing a major threat to public health. Recently, a new influenza D virus (IDV) was isolated from pigs and cattle. Here, we reveal that the IDV utilizes 9-O-acetylated sialic acids as its receptor for virus entry. Then, we determined the crystal structures of hemagglutinin-esterase-fusion glycoprotein (HEF) of IDV both in its free form and in complex with the receptor and enzymatic substrate analogs. The IDV HEF shows an extremely similar structural fold as the human-infecting influenza C virus (ICV) HEF. However, IDV HEF has an open receptor-binding cavity to accommodate diverse extended glycan moieties. This structural difference provides an explanation for the phenomenon that the IDV has a broad cell tropism. As IDV HEF is structurally and functionally similar to ICV HEF, our findings highlight the potential threat of the virus to public health.",2016 Jan 27,"['Song, Hao', 'Qi, Jianxun', 'Khedri, Zahra', 'Diaz, Sandra', 'Yu, Hai', 'Chen, Xi', 'Varki, Ajit', 'Shi, Yi', 'Gao, George F.']",PLoS Pathog,,,True
c23d0e5107a2764e299a147d41a8c76ce91c231d,PMC,Sequence-based approach for rapid identification of cross-clade CD8+ T-cell vaccine candidates from all high-risk HPV strains,http://dx.doi.org/10.1007/s13205-015-0352-z,PMC4729761,28330110,CC BY,"Human papilloma virus (HPV) is the primary etiological agent responsible for cervical cancer in women. Although in total 16 high-risk HPV strains have been identified so far. Currently available commercial vaccines are designed by targeting mainly HPV16 and HPV18 viral strains as these are the most common strains associated with cervical cancer. Because of the high level of antigenic specificity of HPV capsid antigens, the currently available vaccines are not suitable to provide cross-protection from all other high-risk HPV strains. Due to increasing reports of cervical cancer cases from other HPV high-risk strains other than HPV16 and 18, it is crucial to design vaccine that generate reasonable CD8+ T-cell responses for possibly all the high-risk strains. With this aim, we have developed a computational workflow to identify conserved cross-clade CD8+ T-cell HPV vaccine candidates by considering E1, E2, E6 and E7 proteins from all the high-risk HPV strains. We have identified a set of 14 immunogenic conserved peptide fragments that are supposed to provide protection against infection from any of the high-risk HPV strains across globe. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13205-015-0352-z) contains supplementary material, which is available to authorized users.",2016 Jun 27,"['Singh, Krishna P.', 'Verma, Neeraj', 'Akhoon, Bashir A.', 'Bhatt, Vishal', 'Gupta, Shishir K.', 'Gupta, Shailendra K.', 'Smita, Suchi']",3 Biotech,,,True
2bc8716c8d60412f241f096246127275b734635b,PMC,Education to Action: Improving Public Perception of Bats,http://dx.doi.org/10.3390/ani6010006,PMC4730123,26784239,CC BY,"Public perception of bats has historically been largely negative with bats often portrayed as carriers of disease. Bats are commonly associated with vampire lore and thus elicit largely fearful reactions despite the fact that they are a vital and valuable part of the ecosystem. Bats provide a variety of essential services from pest control to plant pollination. Despite the benefits of bats to the environment and the economy, bats are suffering at the hands of humans. They are victims of turbines, human encroachment, pesticides, and, most recently, white nose syndrome. Because of their critical importance to the environment, humans should do what they can to help protect bats. We propose that humans will be more likely to do so if their perceptions and attitudes toward bats can be significantly improved. In a preliminary study we found some support for the idea that people can be educated about bats through bat oriented events and exhibits, and that this greater knowledge can inspire humans to act to save bats.",2016 Jan 15,"['Hoffmaster, Eric', 'Vonk, Jennifer', 'Mies, Rob']",Animals (Basel),,,True
3f21f365d6a8983fd6cf0406c66d2785d0c3a138,PMC,The Roles of RNase-L in Antimicrobial Immunity and the Cytoskeleton-Associated Innate Response,http://dx.doi.org/10.3390/ijms17010074,PMC4730318,26760998,CC BY,"The interferon (IFN)-regulated endoribonuclease RNase-L is involved in multiple aspects of the antimicrobial innate immune response. It is the terminal component of an RNA cleavage pathway in which dsRNA induces the production of RNase-L-activating 2-5A by the 2′-5′-oligoadenylate synthetase. The active nuclease then cleaves ssRNAs, both cellular and viral, leading to downregulation of their expression and the generation of small RNAs capable of activating retinoic acid-inducible gene-I (RIG-I)-like receptors or the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome. This leads to IFNβ expression and IL-1β activation respectively, in addition to broader effects on immune cell function. RNase-L is also one of a growing number of innate immune components that interact with the cell cytoskeleton. It can bind to several cytoskeletal proteins, including filamin A, an actin-binding protein that collaborates with RNase-L to maintain the cellular barrier to viral entry. This antiviral activity is independent of catalytic function, a unique mechanism for RNase-L. We also describe here the interaction of RNase-L with the E3 ubiquitin ligase and scaffolding protein, ligand of nump protein X (LNX), a regulator of tight junction proteins. In order to better understand the significance and context of these novel binding partners in the antimicrobial response, other innate immune protein interactions with the cytoskeleton are also discussed.",2016 Jan 8,"['Ezelle, Heather J.', 'Malathi, Krishnamurthy', 'Hassel, Bret A.']",Int J Mol Sci,,,True
eb856c32c1a41e6513729e126e84e639ce4f5a68,PMC,Prevalence and risk factors for viral exposure in rural dogs around protected areas of the Atlantic forest,http://dx.doi.org/10.1186/s12917-016-0646-3,PMC4730773,26822375,CC BY,"BACKGROUND: Despite the crucial role of domestic dogs as reservoirs for zoonosis and some of the most threatening diseases for wild carnivores such as distemper and parvovirosis, little is known about the epidemiological features and the risk factors involved in pathogen exposure of dogs that live in human/wildlife interfaces and actually contacts wildlife. Through a cross-sectional serological approach and questionnaire survey, we assessed the prevalence along with individual and environment-associated risk factors for four important viral diseases of rural dogs living in households around six Atlantic Forest fragments in southeast Brazil. RESULTS: Widespread exposure to canine parvovirus (97 %), canine distemper virus (15 %) and canine adenovirus (27 %) was detected, but none for canine coronavirus. Dogs from small private reserves were more exposed to parvovirus and canine distemper virus than those from larger state parks. Exposure was associated with dog sex and age, lack of health care and the number of people in the households. Remarkably, factors linked to free-ranging behaviour of dogs were associated with the exposure for all pathogens detected. CONCLUSIONS: According to identified associations, reducing viral pathogen exposure in dogs will require inhibiting dog’s movements and access to nearby forests and villages and improving veterinary assistance. Promoting dog vaccination and population control through sterilization around protected areas is also necessary. The study provides support for preventive management actions aimed to protect the health of rural dogs, and consequently of Atlantic Forest’s wild carnivores.",2016 Jan 28,"['Curi, Nelson Henrique de Almeida', 'Massara, Rodrigo Lima', 'de Oliveira Paschoal, Ana Maria', 'Soriano-Araújo, Amanda', 'Lobato, Zélia Inês Portela', 'Demétrio, Guilherme Ramos', 'Chiarello, Adriano Garcia', 'Passamani, Marcelo']",BMC Vet Res,,,True
5bb362d1be223686ad4467e317cf5abb8383ab3e,PMC,"Acute Uncomplicated Febrile Illness in Children Aged 2-59 months in Zanzibar – Aetiologies, Antibiotic Treatment and Outcome",http://dx.doi.org/10.1371/journal.pone.0146054,PMC4731140,26821179,CC BY,"BACKGROUND: Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission. METHODS: We prospectively studied the aetiology of febrile illness in 677 children aged 2–59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q)PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated. FINDINGS: NPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection retrospectively considered to require antibiotics. Clinical outcome was generally good. However, two children died. Only 68 (11%) patients remained febrile on day 3 and three of them had verified fever on day 14. An additional 29 (4.5%) children had fever relapse on day 14. Regression analysis determined C-reactive Protein (CRP) as the only independent variable significantly associated with CXR-confirmed pneumonia. CONCLUSIONS: This is the first study on uncomplicated febrile illness in African children that both applied a comprehensive laboratory panel and a healthy control group. A majority of patients had viral respiratory tract infection. Pathogens were frequently detected by qPCR also in asymptomatic children, demonstrating the importance of incorporating controls in fever aetiology studies. The precision of IMCI for identifying infections requiring antibiotics was low.",2016 Jan 28,"['Elfving, Kristina', 'Shakely, Deler', 'Andersson, Maria', 'Baltzell, Kimberly', 'Ali, Abdullah S.', 'Bachelard, Marc', 'Falk, Kerstin I.', 'Ljung, Annika', 'Msellem, Mwinyi I.', 'Omar, Rahila S.', 'Parola, Philippe', 'Xu, Weiping', 'Petzold, Max', 'Trollfors, Birger', 'Björkman, Anders', 'Lindh, Magnus', 'Mårtensson, Andreas']",PLoS One,,,True
926c0d5330eefdb58452c054c8387da92e9d0590,PMC,Experimental feline enteric coronavirus infection reveals an aberrant infection pattern and shedding of mutants with impaired infectivity in enterocyte cultures,http://dx.doi.org/10.1038/srep20022,PMC4731813,26822958,CC BY,"Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection. Since many virological and immunological data on FECV infections are lacking, the present study investigated these missing links during experimental infection of three SPF cats with FECV strain UCD. Two cats showed mild clinical signs, faecal shedding of infectious virus from 4 dpi, a cell-associated viraemia at inconsistent time points from 5 dpi, a highly neutralising antibody response from 9 dpi, and no major abnormalities in leukocyte numbers. Faecal shedding lasted for 28–56 days, but virus shed during this stage was less infectious in enterocyte cultures and affected by mutations. Remarkably, in the other cat neither clinical signs nor acute shedding were seen, but virus was detected in blood cells from 3 dpi, and shedding of non-enterotropic, mutated viruses suddenly occurred from 14 dpi onwards. Neutralising antibodies arose from 21 dpi. Leukocyte numbers were not different compared to the other cats, except for the CD8(+) regulatory T cells. These data indicate that FECV can infect immune cells even in the absence of intestinal replication and raise the hypothesis that the gradual adaptation to these cells can allow non-enterotropic mutants to arise.",2016 Jan 29,"['Desmarets, Lowiese M. B.', 'Vermeulen, Ben L.', 'Theuns, Sebastiaan', 'Conceição-Neto, Nádia', 'Zeller, Mark', 'Roukaerts, Inge D. M.', 'Acar, Delphine D.', 'Olyslaegers, Dominique A. J.', 'Van Ranst, Marc', 'Matthijnssens, Jelle', 'Nauwynck, Hans J.']",Sci Rep,,,True
77d34e9158807dab65379240836e8a73dd02e2d2,PMC,Construction of the influenza A virus transmission tree in a college-based population: co-transmission and interactions between influenza A viruses,http://dx.doi.org/10.1186/s12879-016-1373-x,PMC4731987,26825326,CC BY,"BACKGROUND: Co-infection of different influenza A viruses is known to occur but how viruses interact within co-infection remains unknown. An outbreak in a college campus during the 2009 pandemic involved two subtypes of influenza A: persons infected with pandemic A/H1N1; persons infected with seasonal A/H3N2 viruses; and persons infected with both at the same time (co-infection). This provides data to analyse the possible interaction between influenza A viruses within co-infection. METHODS: We extend a statistical inference method designed for outbreaks caused by one virus to that caused by two viruses. The method uses knowledge of which subtype each case is infected with (and whether they were co-infected), contact information and symptom onset date of each case in the influenza outbreak. We then apply it to construct the most likely transmission tree during the outbreak in the college campus. RESULTS: Analysis of the constructed transmission tree shows that the simultaneous presence of the two influenza viruses increases the infectivity and the transmissibility of A/H1N1 virus but whether it changes the infectivity of A/H3N2 is unclear. The estimation also shows that co-transmission of both subtypes from co-infection is low and therefore co-infection cannot be sustained on its own. CONCLUSIONS: This study suggests that influenza A viruses within co-infected patients can interact in some ways rather than transmit independently, and this can enhance the spread of influenza A virus infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1373-x) contains supplementary material, which is available to authorized users.",2016 Jan 29,"['Zhang, Xu-Sheng', 'De Angelis, Daniela']",BMC Infect Dis,,,True
55a2b6184753d85b19f0425ac2d68868e73248b7,PMC,Use of Piezoelectric Immunosensors for Detection of Interferon-Gamma Interaction with Specific Antibodies in the Presence of Released-Active Forms of Antibodies to Interferon-Gamma,http://dx.doi.org/10.3390/s16010096,PMC4732129,26791304,CC BY,"In preliminary ELISA studies where released-active forms (RAF) of antibodies (Abs) to interferon-gamma (IFNg) were added to the antigen-antibody system, a statistically significant difference in absorbance signals obtained in their presence in comparison to placebo was observed. A piezoelectric immunosensor assay was developed to support these data and investigate the effects of RAF Abs to IFNg on the specific interaction between Abs to IFNg and IFNg. The experimental conditions were designed and optimal electrode coating, detection circumstances and suitable chaotropic agents for electrode regeneration were selected. The developed technique was found to provide high repeatability, intermediate precision and specificity. The difference between the analytical signals of RAF Ab samples and those of the placebo was up to 50.8%, whereas the difference between non-specific controls and the placebo was within 5%–6%. Thus, the piezoelectric immunosensor as well as ELISA has the potential to be used for detecting the effects of RAF Abs to IFNg on the antigen-antibody interaction, which might be the result of RAF’s ability to modify the affinity of IFNg to specific/related Abs.",2016 Jan 20,"['Don, Elena', 'Farafonova, Olga', 'Pokhil, Suzanna', 'Barykina, Darya', 'Nikiforova, Marina', 'Shulga, Darya', 'Borshcheva, Alena', 'Tarasov, Sergey', 'Ermolaeva, Tatyana', 'Epstein, Oleg']",Sensors (Basel),,,True
81efe68611a25f79f0f485a2116a213080a38233,PMC,Use of Piezoelectric Immunosensors for Detection of Interferon-Gamma Interaction with Specific Antibodies in the Presence of Released-Active Forms of Antibodies to Interferon-Gamma,http://dx.doi.org/10.3390/s16010096,PMC4732129,26791304,CC BY,"In preliminary ELISA studies where released-active forms (RAF) of antibodies (Abs) to interferon-gamma (IFNg) were added to the antigen-antibody system, a statistically significant difference in absorbance signals obtained in their presence in comparison to placebo was observed. A piezoelectric immunosensor assay was developed to support these data and investigate the effects of RAF Abs to IFNg on the specific interaction between Abs to IFNg and IFNg. The experimental conditions were designed and optimal electrode coating, detection circumstances and suitable chaotropic agents for electrode regeneration were selected. The developed technique was found to provide high repeatability, intermediate precision and specificity. The difference between the analytical signals of RAF Ab samples and those of the placebo was up to 50.8%, whereas the difference between non-specific controls and the placebo was within 5%–6%. Thus, the piezoelectric immunosensor as well as ELISA has the potential to be used for detecting the effects of RAF Abs to IFNg on the antigen-antibody interaction, which might be the result of RAF’s ability to modify the affinity of IFNg to specific/related Abs.",2016 Jan 20,"['Don, Elena', 'Farafonova, Olga', 'Pokhil, Suzanna', 'Barykina, Darya', 'Nikiforova, Marina', 'Shulga, Darya', 'Borshcheva, Alena', 'Tarasov, Sergey', 'Ermolaeva, Tatyana', 'Epstein, Oleg']",Sensors (Basel),,,False
585a9f7b2e41ffc6ead4df982ba9d0b0adb28f51,PMC,Self-disseminating vaccines for emerging infectious diseases,http://dx.doi.org/10.1586/14760584.2016.1106942,PMC4732410,26524478,CC BY,"Modern human activity fueled by economic development is profoundly altering our relationship with microorganisms. This altered interaction with microbes is believed to be the major driving force behind the increased rate of emerging infectious diseases from animals. The spate of recent infectious disease outbreaks, including Ebola virus disease and Middle East respiratory syndrome, emphasize the need for development of new innovative tools to manage these emerging diseases. Disseminating vaccines are one such novel approach to potentially interrupt animal to human (zoonotic) transmission of these pathogens.",2016 Jan 2,"['Murphy, Aisling A.', 'Redwood, Alec J.', 'Jarvis, Michael A.']",Expert Rev Vaccines,,,True
10a9a18d6d821b917178be32b20f98c9e21d6028,PMC,A Novel High-Throughput Method for Molecular Detection of Human Pathogenic Viruses Using a Nanofluidic Real-Time PCR System,http://dx.doi.org/10.1371/journal.pone.0147832,PMC4732599,26824897,CC BY,"Human enteric viruses are recognized as the main causes of food- and waterborne diseases worldwide. Sensitive and quantitative detection of human enteric viruses is typically achieved through quantitative RT-PCR (RT-qPCR). A nanofluidic real-time PCR system was used to develop novel high-throughput methods for qualitative molecular detection (RT-qPCR array) and quantification of human pathogenic viruses by digital RT-PCR (RT-dPCR). The performance of high-throughput PCR methods was investigated for detecting 19 human pathogenic viruses and two main process controls used in food virology. The conventional real-time PCR system was compared to the RT-dPCR and RT-qPCR array. Based on the number of genome copies calculated by spectrophotometry, sensitivity was found to be slightly better with RT-qPCR than with RT-dPCR for 14 viruses by a factor range of from 0.3 to 1.6 log(10). Conversely, sensitivity was better with RT-dPCR than with RT-qPCR for seven viruses by a factor range of from 0.10 to 1.40 log(10). Interestingly, the number of genome copies determined by RT-dPCR was always from 1 to 2 log(10) lower than the expected copy number calculated by RT-qPCR standard curve. The sensitivity of the RT-qPCR and RT-qPCR array assays was found to be similar for two viruses, and better with RT-qPCR than with RT-qPCR array for eighteen viruses by a factor range of from 0.7 to 3.0 log(10). Conversely, sensitivity was only 0.30 log(10) better with the RT-qPCR array than with conventional RT-qPCR assays for norovirus GIV detection. Finally, the RT-qPCR array and RT-dPCR assays were successfully used together to screen clinical samples and quantify pathogenic viruses. Additionally, this method made it possible to identify co-infection in clinical samples. In conclusion, given the rapidity and potential for large numbers of viral targets, this nanofluidic RT-qPCR assay should have a major impact on human pathogenic virus surveillance and outbreak investigations and is likely to be of benefit to public health.",2016 Jan 29,"['Coudray-Meunier, Coralie', 'Fraisse, Audrey', 'Martin-Latil, Sandra', 'Delannoy, Sabine', 'Fach, Patrick', 'Perelle, Sylvie']",PLoS One,,,True
8826961991932d2c6c8f72d0ad2b02a625faa4f5,PMC,"Characterization of Rv0888, a Novel Extracellular Nuclease from Mycobacterium tuberculosis",http://dx.doi.org/10.1038/srep19033,PMC4733049,26742696,CC BY,"Bacterial extracellular nucleases play important roles in virulence, biofilm formation, utilization of extracellular DNA as a nutrient, and degradation of neutrophil DNA extracellular traps. However, there is no current data available for extracellular nucleases derived from M. tuberculosis. Herein, we have identified and characterized Rv0888, an extracellular nuclease in M. tuberculosis. The protein was overexpressed in E. coli, and the purified Rv0888 protein was found to require divalent cations for activity, with an optimal temperature and pH of 41 °C and 6.5, respectively. Further results demonstrated that Rv0888 nuclease activity could be inhibited by four Chinese medicine monomers. Based on sequence analysis, Rv0888 nuclease exhibited no homology with any known extracellular nucleases, indicating that Rv0888 is a novel nuclease. Site-directed mutagenesis studies revealed that the H353, D387, and D438 residues play catalytic roles in Rv0888. In vivo infection studies confirmed that Rv0888 is required for infection and is related to pathogenicity, as the persistent ability of recombinant Mycobacterium smegmatis (rMS) Rv0888NS/MS and Rv0888S/MS is significantly higher than pMV262/MS in the lung tissue, and the Rv0888NS/MS and Rv0888S/MS could produce pathological changes in the mice lung. These results show that Rv0888 is relevant to pathogenicity of M. tuberculosis.",2016 Jan 8,"['Dang, Guanghui', 'Cao, Jun', 'Cui, Yingying', 'Song, Ningning', 'Chen, Liping', 'Pang, Hai', 'Liu, Siguo']",Sci Rep,,,True
d18e10321c54248f5fdfdac2501f5368ac8052c7,PMC,Neuropathogenicity of Two Saffold Virus Type 3 Isolates in Mouse Models,http://dx.doi.org/10.1371/journal.pone.0148184,PMC4734772,26828718,CC BY,"OBJECTIVE: Saffold virus (SAFV), a picornavirus, is occasionally detected in children with acute flaccid paralysis, meningitis, and cerebellitis; however, the neuropathogenicity of SAFV remains undetermined. METHODS: The virulence of two clinical isolates of SAFV type 3 (SAFV-3) obtained from a patient with aseptic meningitis (AM strain) and acute upper respiratory inflammation (UR strain) was analyzed in neonatal and young mice utilizing virological, pathological, and immunological methods. RESULTS: The polyproteins of the strains differed in eight amino acids. Both clinical isolates were infective, exhibited neurotropism, and were mildly neurovirulent in neonatal ddY mice. Both strains pathologically infected neural progenitor cells and glial cells, but not large neurons, with the UR strain also infecting epithelial cells. UR infection resulted in longer inflammation in the brain and spinal cord because of demyelination, while the AM strain showed more infectivity in the cerebellum in neonatal ddY mice. Additionally, young BALB/c mice seroconverted following mucosal inoculation with the UR, but not the AM, strain. CONCLUSIONS: Both SAFV-3 isolates had neurotropism and mild neurovirulence but showed different cell tropisms in both neonatal and young mouse models. This animal model has the potential to recapitulate the potential neuropathogenicity of SAFV-3.",2016 Feb 1,"['Kotani, Osamu', 'Naeem, Asif', 'Suzuki, Tadaki', 'Iwata-Yoshikawa, Naoko', 'Sato, Yuko', 'Nakajima, Noriko', 'Hosomi, Takushi', 'Tsukagoshi, Hiroyuki', 'Kozawa, Kunihisa', 'Hasegawa, Hideki', 'Taguchi, Fumihiro', 'Shimizu, Hiroyuki', 'Nagata, Noriyo']",PLoS One,,,True
c481fdcf995099e14997dabd9fe3b47ce8784020,PMC,Prevalence and characteristics of hypoxic hepatitis in the largest single-centre cohort of avian influenza A(H7N9) virus-infected patients with severe liver impairment in the intensive care unit,http://dx.doi.org/10.1038/emi.2016.1,PMC4735056,26733380,CC BY,"Avian influenza A(H7N9) virus (A(H7N9)) emerged in February 2013. Liver impairment of unknown cause is present in 29% of patients with A(H7N9) infection, some of whom experience severe liver injury. Hypoxic hepatitis (HH) is a type of acute severe liver injury characterized by an abrupt, massive increase in serum aminotransferases resulting from anoxic centrilobular necrosis of liver cells. In the intensive care unit (ICU), the prevalence of HH is ∼1%–2%. Here, we report a 1.8% (2/112) incidence of HH in the largest single-centre cohort of ICU patients with A(H7N9) infection. Both HH patients presented with multiple organ failure (MOF) involving respiratory, cardiac, circulatory and renal failure and had a history of chronic heart disease. On admission, severe liver impairment was found. Peak alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values were 937 and 1281 U/L, and 3117 and 3029 U/L, respectively, in the two patients. Unfortunately, both patients died due to deterioration of MOF. A post-mortem biopsy in case 1 confirmed the presence of centrilobular necrosis of the liver, and real-time reverse transcription polymerase chain reaction of A(H7N9)-specific genes was negative, which excluded A(H7N9)-related hepatitis. The incidence of HH in A(H7N9) patients is similar to that in ICU patients with other aetiologies. It seems that patients with A(H7N9) infection and a history of chronic heart disease with a low left ventricular ejection fraction on admission are susceptible to HH, which presents as a marked elevation in ALT at the time of admission.",2016 Jan 6,"['Zhang, YiMin', 'Liu, JiMin', 'Yu, Liang', 'Zhou, Ning', 'Ding, Wei', 'Zheng, ShuFa', 'Shi, Ding', 'Li, LanJuan']",Emerg Microbes Infect,,,True
525c07cc621b7185fb0d224710d883f523d08ba3,PMC,"Molecular characterization of human coronaviruses and their circulation dynamics in Kenya, 2009–2012",http://dx.doi.org/10.1186/s12985-016-0474-x,PMC4736488,26833249,CC BY,"BACKGROUND: Human Coronaviruses (HCoV) are a common cause of respiratory illnesses and are responsible for considerable morbidity and hospitalization across all age groups especially in individuals with compromised immunity. There are six known species of HCoV: HCoV-229E, HCoV-NL63, HCoV-HKU1, HCoV-OC43, MERS-CoV and SARS-HCoV. Although studies have shown evidence of global distribution of HCoVs, there is limited information on their presence and distribution in Kenya. METHODS: HCoV strains that circulated in Kenya were retrospectively diagnosed and molecularly characterized. A total of 417 nasopharyngeal specimens obtained between January 2009 and December 2012 from around Kenya were analyzed by a real time RT-PCR using HCoV-specific primers. HCoV-positive specimens were subsequently inoculated onto monolayers of LL-CMK2 cells. The isolated viruses were characterized by RT-PCR amplification and sequencing of the partial polymerase (pol) gene. RESULTS: The prevalence of HCoV infection was as follows: out of the 417 specimens, 35 (8.4 %) were positive for HCoV, comprising 10 (2.4 %) HCoV-NL63, 12 (2.9 %) HCoV-OC43, 9 (2.1 %) HCoV-HKU1, and 4 (1 %) HCoV-229E. The Kenyan HCoV strains displayed high sequence homology to the prototypes and contemporaneous strains. Evolution analysis showed that the Kenyan HCoV-OC43 and HCoV-NL63 isolates were under purifying selection. Phylogenetic evolutionary analyses confirmed the identities of three HCoV-HKU1, five HCoV-NL63, eight HCoV-OC43 and three HCoV-229E. CONCLUSIONS: There were yearly variations in the prevalence and circulation patterns of individual HCoVs in Kenya. This paper reports on the first molecular characterization of human Coronaviruses in Kenya, which play an important role in causing acute respiratory infections among children.",2016 Feb 1,"['Sipulwa, Lenata A.', 'Ongus, Juliette R.', 'Coldren, Rodney L.', 'Bulimo, Wallace D.']",Virol J,,,True
e745a55d651d2f45443c39ed949185d8f968500a,PMC,Multiple Cis-acting elements modulate programmed -1 ribosomal frameshifting in Pea enation mosaic virus,http://dx.doi.org/10.1093/nar/gkv1241,PMC4737148,26578603,CC BY,"Programmed -1 ribosomal frameshifting (-1 PRF) is used by many positive-strand RNA viruses for translation of required products. Despite extensive studies, it remains unresolved how cis-elements just downstream of the recoding site promote a precise level of frameshifting. The Umbravirus Pea enation mosaic virus RNA2 expresses its RNA polymerase by -1 PRF of the 5′-proximal ORF (p33). Three hairpins located in the vicinity of the recoding site are phylogenetically conserved among Umbraviruses. The central Recoding Stimulatory Element (RSE), located downstream of the p33 termination codon, is a large hairpin with two asymmetric internal loops. Mutational analyses revealed that sequences throughout the RSE and the RSE lower stem (LS) structure are important for frameshifting. SHAPE probing of mutants indicated the presence of higher order structure, and sequences in the LS may also adapt an alternative conformation. Long-distance pairing between the RSE and a 3′ terminal hairpin was less critical when the LS structure was stabilized. A basal level of frameshifting occurring in the absence of the RSE increases to 72% of wild-type when a hairpin upstream of the slippery site is also deleted. These results suggest that suppression of frameshifting may be needed in the absence of an active RSE conformation.",2016 Jan 29,"['Gao, Feng', 'Simon, Anne E.']",Nucleic Acids Res,,,True
8c2e819ffac93b6796d3d9fdf7ccc8e67c397a31,PMC,Domain swapping oligomerization of thermostable c-type cytochrome in E. coli cells,http://dx.doi.org/10.1038/srep19334,PMC4738263,26838805,CC BY,"Knowledge on domain swapping in vitro is increasing, but domain swapping may not occur regularly in vivo, and its information in cells is limited. Herein, we show that domain-swapped oligomers of a thermostable c-type cytochrome, Hydrogenobacter thermophilus cyt c(552), are formed in E. coli which expresses cyt c(552). The region containing the N-terminal α-helix and heme was domain-swapped between protomers in the dimer formed in E. coli. The amount of cyt c(552) oligomers increased in E. coli as the cyt c(552) concentration was increased, whereas that of high-order oligomers decreased in the order of decrease in protein stability, indicating that domain swapping decreases in cells when the protein stability decreases. Apo cyt c(552) was detected in the cyt c(552) oligomer formed in E. coli, but not in that of the A5F/M11V/Y32F/Y41E/I76V mutant. The cyt c(552) oligomer containing its apo protein may form at the periplasm, since the apo protein detected by mass measurements did not contain the signal peptide. These results show that domain-swapped cyt c(552) oligomers were formed in E. coli, owing to the stability of the transient oligomer containing the apo protein before heme attachment. This is an indication that exceedingly stable proteins may have disadvantages forming domain-swapped oligomers in cells.",2016 Feb 3,"['Hayashi, Yugo', 'Yamanaka, Masaru', 'Nagao, Satoshi', 'Komori, Hirofumi', 'Higuchi, Yoshiki', 'Hirota, Shun']",Sci Rep,,,True
4c5661848b054307106bd3b67311da7effd797a8,PMC,Domain swapping oligomerization of thermostable c-type cytochrome in E. coli cells,http://dx.doi.org/10.1038/srep19334,PMC4738263,26838805,CC BY,"Knowledge on domain swapping in vitro is increasing, but domain swapping may not occur regularly in vivo, and its information in cells is limited. Herein, we show that domain-swapped oligomers of a thermostable c-type cytochrome, Hydrogenobacter thermophilus cyt c(552), are formed in E. coli which expresses cyt c(552). The region containing the N-terminal α-helix and heme was domain-swapped between protomers in the dimer formed in E. coli. The amount of cyt c(552) oligomers increased in E. coli as the cyt c(552) concentration was increased, whereas that of high-order oligomers decreased in the order of decrease in protein stability, indicating that domain swapping decreases in cells when the protein stability decreases. Apo cyt c(552) was detected in the cyt c(552) oligomer formed in E. coli, but not in that of the A5F/M11V/Y32F/Y41E/I76V mutant. The cyt c(552) oligomer containing its apo protein may form at the periplasm, since the apo protein detected by mass measurements did not contain the signal peptide. These results show that domain-swapped cyt c(552) oligomers were formed in E. coli, owing to the stability of the transient oligomer containing the apo protein before heme attachment. This is an indication that exceedingly stable proteins may have disadvantages forming domain-swapped oligomers in cells.",2016 Feb 3,"['Hayashi, Yugo', 'Yamanaka, Masaru', 'Nagao, Satoshi', 'Komori, Hirofumi', 'Higuchi, Yoshiki', 'Hirota, Shun']",Sci Rep,,,True
278697db1668e58b24cd105be09208d7f1bc1119,PMC,Respiratory Viruses Associated Hospitalization among Children Aged <5 Years in Bangladesh: 2010-2014,http://dx.doi.org/10.1371/journal.pone.0147982,PMC4739641,26840782,CC0,"BACKGROUND: We combined hospital-based surveillance and health utilization survey data to estimate the incidence of respiratory viral infections associated hospitalization among children aged < 5 years in Bangladesh. METHODS: Surveillance physicians collected respiratory specimens from children aged <5 years hospitalized with respiratory illness and residing in the primary hospital catchment areas. We tested respiratory specimens for respiratory syncytial virus, parainfluenza viruses, human metapneumovirus, influenza, adenovirus and rhinoviruses using rRT-PCR. During 2013, we conducted a health utilization survey in the primary catchment areas of the hospitals to determine the proportion of all hospitalizations for respiratory illness among children aged <5 years at the surveillance hospitals during the preceding 12 months. We estimated the respiratory virus-specific incidence of hospitalization by dividing the estimated number of hospitalized children with a laboratory confirmed infection with a respiratory virus by the population aged <5 years of the catchment areas and adjusted for the proportion of children who were hospitalized at the surveillance hospitals. RESULTS: We estimated that the annual incidence per 1000 children (95% CI) of all cause associated respiratory hospitalization was 11.5 (10–12). The incidences per 1000 children (95% CI) per year for respiratory syncytial virus, parainfluenza, adenovirus, human metapneumovirus and influenza infections were 3(2–3), 0.5(0.4–0.8), 0.4 (0.3–0.6), 0.4 (0.3–0.6), and 0.4 (0.3–0.6) respectively. The incidences per 1000 children (95%CI) of rhinovirus-associated infections among hospitalized children were 5 (3–7), 2 (1–3), 1 (0.6–2), and 3 (2–4) in 2010, 2011, 2012 and 2013, respectively. CONCLUSION: Our data suggest that respiratory viruses are associated with a substantial burden of hospitalization in children aged <5 years in Bangladesh.",2016 Feb 3,"['Homaira, Nusrat', 'Luby, Stephen P.', 'Hossain, Kamal', 'Islam, Kariul', 'Ahmed, Makhdum', 'Rahman, Mustafizur', 'Rahman, Ziaur', 'Paul, Repon C.', 'Bhuiyan, Mejbah Uddin', 'Brooks, W. Abdullah', 'Sohel, Badrul Munir', 'Banik, Kajal Chandra', 'Widdowson, Marc-Alain', 'Willby, Melisa', 'Rahman, Mahmudur', 'Bresee, Joseph', 'Ramirez, Katharine-Sturm', 'Azziz-Baumgartner, Eduardo']",PLoS One,,,True
b2511d6e6a5faa918701cd2bf6e2641ba7f4c9cd,PMC,Epstein- Barr Virus: Clinical and Epidemiological Revisits and Genetic Basis of Oncogenesis,http://dx.doi.org/10.2174/1874357901509010007,PMC4740969,26862355,CC BY,"Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancies",2015 Nov 3,"['Ali, Abdelwahid Saeed', 'Al-Shraim, Mubarak', 'Al-Hakami, Ahmed Musa', 'Jones, Ian M']",Open Virol J,,,True
4ef6fc1277c3190055c77131bd2030f18ecb54ac,PMC,Antigen Production in Plant to Tackle Infectious Diseases Flare Up: The Case of SARS,http://dx.doi.org/10.3389/fpls.2016.00054,PMC4742786,26904039,CC BY,"Severe acute respiratory syndrome (SARS) is a dangerous infection with pandemic potential. It emerged in 2002 and its aetiological agent, the SARS Coronavirus (SARS-CoV), crossed the species barrier to infect humans, showing high morbidity and mortality rates. No vaccines are currently licensed for SARS-CoV and important efforts have been performed during the first outbreak to develop diagnostic tools. Here we demonstrate the transient expression in Nicotiana benthamiana of two important antigenic determinants of the SARS-CoV, the nucleocapsid protein (N) and the membrane protein (M) using a virus-derived vector or agro-infiltration, respectively. For the M protein, this is the first description of production in plants, while for plant-derived N protein we demonstrate that it is recognized by sera of patients from the SARS outbreak in Hong Kong in 2003. The availability of recombinant N and M proteins from plants opens the way to further evaluation of their potential utility for the development of diagnostic and protection/therapy tools to be quickly manufactured, at low cost and with minimal risk, to face potential new highly infectious SARS-CoV outbreaks.",2016 Feb 5,"['Demurtas, Olivia C.', 'Massa, Silvia', 'Illiano, Elena', 'De Martinis, Domenico', 'Chan, Paul K. S.', 'Di Bonito, Paola', 'Franconi, Rosella']",Front Plant Sci,,,True
cc66ac23fd5a72e5bf95bad4be77eb93527562d9,PMC,"Estimation of the Basic Reproductive Number and Mean Serial Interval of a Novel Pathogen in a Small, Well-Observed Discrete Population",http://dx.doi.org/10.1371/journal.pone.0148061,PMC4744020,26849644,CC BY,"BACKGROUND: Accurately assessing the transmissibility and serial interval of a novel human pathogen is public health priority so that the timing and required strength of interventions may be determined. Recent theoretical work has focused on making best use of data from the initial exponential phase of growth of incidence in large populations. METHODS: We measured generational transmissibility by the basic reproductive number R(0) and the serial interval by its mean T(g). First, we constructed a simulation algorithm for case data arising from a small population of known size with R(0) and T(g) also known. We then developed an inferential model for the likelihood of these case data as a function of R(0) and T(g). The model was designed to capture a) any signal of the serial interval distribution in the initial stochastic phase b) the growth rate of the exponential phase and c) the unique combination of R(0) and T(g) that generates a specific shape of peak incidence when the susceptible portion of a small population is depleted. FINDINGS: Extensive repeat simulation and parameter estimation revealed no bias in univariate estimates of either R(0) and T(g). We were also able to simultaneously estimate both R(0) and T(g). However, accurate final estimates could be obtained only much later in the outbreak. In particular, estimates of T(g) were considerably less accurate in the bivariate case until the peak of incidence had passed. CONCLUSIONS: The basic reproductive number and mean serial interval can be estimated simultaneously in real time during an outbreak of an emerging pathogen. Repeated application of these methods to small scale outbreaks at the start of an epidemic would permit accurate estimates of key parameters.",2016 Feb 5,"['Wu, Kendra M.', 'Riley, Steven']",PLoS One,,,True
39a1d7e4cf03a63037800c831965232d1d259e0f,PMC,Selective Degradation of Host RNA Polymerase II Transcripts by Influenza A Virus PA-X Host Shutoff Protein,http://dx.doi.org/10.1371/journal.ppat.1005427,PMC4744033,26849127,CC BY,"Influenza A viruses (IAVs) inhibit host gene expression by a process known as host shutoff. Host shutoff limits host innate immune responses and may also redirect the translation apparatus to the production of viral proteins. Multiple IAV proteins regulate host shutoff, including PA-X, a ribonuclease that remains incompletely characterized. We report that PA-X selectively targets host RNA polymerase II (Pol II) transcribed mRNAs, while sparing products of Pol I and Pol III. Interestingly, we show that PA-X can also target Pol II-transcribed RNAs in the nucleus, including non-coding RNAs that are not destined to be translated, and reporter transcripts with RNA hairpin structures that block ribosome loading. Transcript degradation likely occurs in the nucleus, as PA-X is enriched in the nucleus and its nuclear localization correlates with reduction in target RNA levels. Complete degradation of host mRNAs following PA-X-mediated endonucleolytic cleavage is dependent on the host 5’->3’-exonuclease Xrn1. IAV mRNAs are structurally similar to host mRNAs, but are synthesized and modified at the 3’ end by the action of the viral RNA-dependent RNA polymerase complex. Infection of cells with wild-type IAV or a recombinant PA-X-deficient virus revealed that IAV mRNAs resist PA-X-mediated degradation during infection. At the same time, loss of PA-X resulted in changes in the synthesis of select viral mRNAs and a decrease in viral protein accumulation. Collectively, these results significantly advance our understanding of IAV host shutoff, and suggest that the PA-X causes selective degradation of host mRNAs by discriminating some aspect of Pol II-dependent RNA biogenesis in the nucleus.",2016 Feb 5,"['Khaperskyy, Denys A.', 'Schmaling, Summer', 'Larkins-Ford, Jonah', 'McCormick, Craig', 'Gaglia, Marta M.']",PLoS Pathog,,,True
a59bbb5dd57d1aa789c638a65a93bb8ed66a5e5e,PMC,Selective Degradation of Host RNA Polymerase II Transcripts by Influenza A Virus PA-X Host Shutoff Protein,http://dx.doi.org/10.1371/journal.ppat.1005427,PMC4744033,26849127,CC BY,"Influenza A viruses (IAVs) inhibit host gene expression by a process known as host shutoff. Host shutoff limits host innate immune responses and may also redirect the translation apparatus to the production of viral proteins. Multiple IAV proteins regulate host shutoff, including PA-X, a ribonuclease that remains incompletely characterized. We report that PA-X selectively targets host RNA polymerase II (Pol II) transcribed mRNAs, while sparing products of Pol I and Pol III. Interestingly, we show that PA-X can also target Pol II-transcribed RNAs in the nucleus, including non-coding RNAs that are not destined to be translated, and reporter transcripts with RNA hairpin structures that block ribosome loading. Transcript degradation likely occurs in the nucleus, as PA-X is enriched in the nucleus and its nuclear localization correlates with reduction in target RNA levels. Complete degradation of host mRNAs following PA-X-mediated endonucleolytic cleavage is dependent on the host 5’->3’-exonuclease Xrn1. IAV mRNAs are structurally similar to host mRNAs, but are synthesized and modified at the 3’ end by the action of the viral RNA-dependent RNA polymerase complex. Infection of cells with wild-type IAV or a recombinant PA-X-deficient virus revealed that IAV mRNAs resist PA-X-mediated degradation during infection. At the same time, loss of PA-X resulted in changes in the synthesis of select viral mRNAs and a decrease in viral protein accumulation. Collectively, these results significantly advance our understanding of IAV host shutoff, and suggest that the PA-X causes selective degradation of host mRNAs by discriminating some aspect of Pol II-dependent RNA biogenesis in the nucleus.",2016 Feb 5,"['Khaperskyy, Denys A.', 'Schmaling, Summer', 'Larkins-Ford, Jonah', 'McCormick, Craig', 'Gaglia, Marta M.']",PLoS Pathog,,,False
e0e1f657eb7a089f3a2fbb4beb3dc6a242a22b34,PMC,Natural Pig Plasma Immunoglobulins Have Anti-Bacterial Effects: Potential for Use as Feed Supplement for Treatment of Intestinal Infections in Pigs,http://dx.doi.org/10.1371/journal.pone.0147373,PMC4744083,26824607,CC BY,"There is an increasing demand for non-antibiotics solutions to control infectious disease in intensive pig production. Here, one such alternative, namely pig antibodies purified from slaughterhouse blood was investigated in order to elucidate its potential usability to control post-weaning diarrhoea (PWD), which is one of the top indications for antibiotics usage in the pig production. A very cost-efficient and rapid one-step expanded bed adsorption (EBA) chromatography procedure was used to purify pig immunoglobulin G from slaughterhouse pig plasma (more than 100 litres), resulting in >85% pure pig IgG (ppIgG). The ppIgG thus comprised natural pig immunoglobulins and was subsequently shown to contain activity towards four pig-relevant bacterial strains (three different types of Escherichia coli and one type of Salmonella enterica) but not towards a fish pathogen (Yersinia ruckeri), and was demonstrated to inhibit the binding of the four pig relevant bacteria to a pig intestinal cell line (IPEC-J2). Finally it was demonstrated in an in vivo weaning piglet model for intestinal colonization with an E. coli F4+ challenge strain that ppIgG given in the feed significantly reduced shedding of the challenge strain, reduced the proportion of the bacterial family Enterobacteriaceae, increased the proportion of families Enterococcoceae and Streptococcaceae and generally increased ileal microbiota diversity. Conclusively, our data support the idea that natural IgG directly purified from pig plasma and given as a feed supplement can be used in modern swine production as an efficient and cost-effective means for reducing both occurrence of PWD and antibiotics usage and with a potential for the prevention and treatment of other intestinal infectious diseases even if the causative agent might not be known.",2016 Jan 29,"['Hedegaard, Chris J.', 'Strube, Mikael L.', 'Hansen, Marie B.', 'Lindved, Bodil K.', 'Lihme, Allan', 'Boye, Mette', 'Heegaard, Peter M. H.']",PLoS One,,,True
a1dde82e18ad108c7eedb452d50a661e647b7cf2,PMC,Coronaviruses and the human airway: a universal system for virus-host interaction studies,http://dx.doi.org/10.1186/s12985-016-0479-5,PMC4744394,26852031,CC BY,"Human coronaviruses (HCoVs) are large RNA viruses that infect the human respiratory tract. The emergence of both Severe Acute Respiratory Syndrome and Middle East Respiratory syndrome CoVs as well as the yearly circulation of four common CoVs highlights the importance of elucidating the different mechanisms employed by these viruses to evade the host immune response, determine their tropism and identify antiviral compounds. Various animal models have been established to investigate HCoV infection, including mice and non-human primates. To establish a link between the research conducted in animal models and humans, an organotypic human airway culture system, that recapitulates the human airway epithelium, has been developed. Currently, different cell culture systems are available to recapitulate the human airways, including the Air-Liquid Interface (ALI) human airway epithelium (HAE) model. Tracheobronchial HAE cultures recapitulate the primary entry point of human respiratory viruses while the alveolar model allows for elucidation of mechanisms involved in viral infection and pathogenesis in the alveoli. These organotypic human airway cultures represent a universal platform to study respiratory virus-host interaction by offering more detailed insights compared to cell lines. Additionally, the epidemic potential of this virus family highlights the need for both vaccines and antivirals. No commercial vaccine is available but various effective antivirals have been identified, some with potential for human treatment. These morphological airway cultures are also well suited for the identification of antivirals, evaluation of compound toxicity and viral inhibition.",2016 Feb 6,"['Jonsdottir, Hulda R.', 'Dijkman, Ronald']",Virol J,,,True
ea97faa57e408d3c7a5b84dbe3da7ae4feb9992e,PMC,"Rapid PCR Detection of Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum",http://dx.doi.org/10.1155/2013/168742,PMC4745450,26904723,CC BY,"Objective. We compared laboratory developed real-time PCR assays for detection of Mycoplasma hominis and for detection and differentiation of Ureaplasma urealyticum and parvum to culture using genitourinary specimens submitted for M. hominis and Ureaplasma culture. Methods. 283 genitourinary specimens received in the clinical bacteriology laboratory for M. hominis and Ureaplasma species culture were evaluated. Nucleic acids were extracted using the Total Nucleic Acid Kit on the MagNA Pure 2.0. 5 μL of the extracts were combined with 15 μL of each of the two master mixes. Assays were performed on the LightCycler 480 II system. Culture was performed using routine methods. Results.   M. hominis PCR detected 38/42 M. hominis culture-positive specimens, as well as 2 that were culture negative (sensitivity, 90.5%; specificity, 99.2%). Ureaplasma PCR detected 139/144 Ureaplasma culture-positive specimens, as well as 9 that were culture negative (sensitivity, 96.5%; specificity, 93.6%). Of the specimens that tested positive for Ureaplasma species, U. urealyticum alone was detected in 33, U. parvum alone in 109, and both in 6. Conclusion. The described PCR assays are rapid alternatives to culture for detection of M. hominis and Ureaplasma species, and, unlike culture, the Ureaplasma assay easily distinguishes U. urealyticum from parvum.",2013 Mar 11,"['Cunningham, Scott A.', 'Mandrekar, Jayawant N.', 'Rosenblatt, Jon E.', 'Patel, Robin']",Int J Bacteriol,,,True
d3630872afc160701dea448dea6409e50b98642f,PMC,Quelling an innate response to dsRNA,,PMC4745674,26356565,CC BY,,2015 Aug 6,"['Ogden, Kristen M.', 'Prasad, B. V. Venkataram']",Oncotarget,,,False
b0e52525fd4deb91e0fc1fd94e9453fddce62905,PMC,Phylogenetic and Pathotypic Characterization of Newcastle Disease Viruses Circulating in South China and Transmission in Different Birds,http://dx.doi.org/10.3389/fmicb.2016.00119,PMC4746259,26903997,CC BY,"Although Newcastle disease virus (NDV) with high pathogenicity has frequently been isolated in poultry in China since 1948, the mode of its transmission among avian species remains largely unknown. Given that various wild bird species have been implicated as sources of transmission, in this study we genotypically and pathotypically characterized 23 NDV isolates collected from chickens, ducks, and pigeons in live bird markets (LBMs) in South China as part of an H7N9 surveillance program during December 2013–February 2014. To simulate the natural transmission of different kinds of animals in LBMs, we selected three representative NDVs—namely, GM, YF18, and GZ289—isolated from different birds to evaluate the pathogenicity and transmission of the indicated viruses in chickens, ducks, and pigeons. Furthermore, to investigate the replication and shedding of NDV in poultry, we inoculated the chickens, ducks, and pigeons with 10(6) EID(50) of each virus via intraocular and intranasal routes. Eight hour after infection, the naïve contact groups were housed with those inoculated with each of the viruses as a means to monitor contact transmission. Our results indicated that genetically diverse viruses circulate in LBMs in South China's Guangdong Province and that NDV from different birds have different tissue tropisms and host ranges when transmitted in different birds. We therefore propose the continuous epidemiological surveillance of LBMs to support the prevention of the spread of these viruses in different birds, especially chickens, and highlight the need for studies of the virus–host relationship.",2016 Feb 9,"['Kang, Yinfeng', 'Xiang, Bin', 'Yuan, Runyu', 'Zhao, Xiaqiong', 'Feng, Minsha', 'Gao, Pei', 'Li, Yanling', 'Li, Yulian', 'Ning, Zhangyong', 'Ren, Tao']",Front Microbiol,,,True
62a1f28a0ad0c2c37252351ad64fd7d8b0efdcc4,PMC,Comparative Analysis of Salivary Gland Proteomes of Two Glossina Species that Exhibit Differential Hytrosavirus Pathologies,http://dx.doi.org/10.3389/fmicb.2016.00089,PMC4746320,26903969,CC BY,"Glossina pallidipes salivary gland hypertrophy virus (GpSGHV; family Hytrosaviridae) is a dsDNA virus exclusively pathogenic to tsetse flies (Diptera; Glossinidae). The 190 kb GpSGHV genome contains 160 open reading frames and encodes more than 60 confirmed proteins. The asymptomatic GpSGHV infection in flies can convert to symptomatic infection that is characterized by overt salivary gland hypertrophy (SGH). Flies with SGH show reduced general fitness and reproductive dysfunction. Although the occurrence of SGH is an exception rather than the rule, G. pallidipes is thought to be the most susceptible to expression of overt SGH symptoms compared to other Glossina species that are largely asymptomatic. Although Glossina salivary glands (SGs) play an essential role in GpSGHV transmission, the functions of the salivary components during the virus infection are poorly understood. In this study, we used mass spectrometry to study SG proteomes of G. pallidipes and G. m. morsitans, two Glossina model species that exhibit differential GpSGHV pathologies (high and low incidence of SGH, respectively). A total of 540 host proteins were identified, of which 23 and 9 proteins were significantly up- and down-regulated, respectively, in G. pallidipes compared to G. m. morsitans. Whereas 58 GpSGHV proteins were detected in G. pallidipes F(1) progenies, only 5 viral proteins were detected in G. m. morsitans. Unlike in G. pallidipes, qPCR assay did not show any significant increase in virus titers in G. m. morsitans F(1) progenies, confirming that G. m. morsitans is less susceptible to GpSGHV infection and replication compared to G. pallidipes. Based on our results, we speculate that in the case of G. pallidipes, GpSGHV employs a repertoire of host intracellular signaling pathways for successful infection. In the case of G. m. morsitans, antiviral responses appeared to be dominant. These results are useful for designing additional tools to investigate the Glossina-GpSGHV interactions.",2016 Feb 9,"['Kariithi, Henry M.', 'İnce, İkbal Agah', 'Boeren, Sjef', 'Murungi, Edwin K.', 'Meki, Irene K.', 'Otieno, Everlyne A.', 'Nyanjom, Steven R. G.', 'van Oers, Monique M.', 'Vlak, Just M.', 'Abd-Alla, Adly M. M.']",Front Microbiol,,,True
481c14a837af6dd6d5a5d8f3a26ae6cc51cca2f6,PMC,Evaluation of twenty‐two rapid antigen detection tests in the diagnosis of Equine Influenza caused by viruses of H3N8 subtype,http://dx.doi.org/10.1111/irv.12358,PMC4746556,26568369,CC BY,"BACKGROUND: Equine influenza (EI) is a highly contagious disease caused by viruses of the H3N8 subtype. The rapid diagnosis of EI is essential to reduce the disease spread. Many rapid antigen detection (RAD) tests for diagnosing human influenza are available, but their ability to diagnose EI has not been systematically evaluated. OBJECTIVES: The aim of this study was to compare the performance of 22 RAD tests in the diagnosis of EI. METHODS: The 22 RAD tests were performed on fivefold serial dilutions of EI virus to determine their detection limits. The four most sensitive RAD tests (ImmunoAce Flu, BD Flu examan, Quick chaser Flu A, B and ESPLINE Influenza A&B‐N) were further evaluated using nasopharyngeal samples collected from experimentally infected and naturally infected horses. The results were compared to those obtained using molecular tests. RESULTS: The detection limits of the 22 RAD tests varied hugely. Even the four RAD tests showing the best sensitivity were 125‐fold less sensitive than the molecular techniques. The duration of virus detection in the experimentally infected horses was shorter using the RAD tests than using the molecular techniques. The RAD tests detected between 27% and 73% of real‐time RT‐PCR‐positive samples from naturally infected horses. CONCLUSIONS: The study demonstrated the importance of choosing the right RAD tests as only three of 22 were fit for diagnosing EI. It was also indicated that even RAD tests with the highest sensitivity serve only as an adjunct to molecular tests because of the potential for false‐negative results.",2016 Mar 1,"['Yamanaka, Takashi', 'Nemoto, Manabu', 'Bannai, Hiroshi', 'Tsujimura, Koji', 'Kondo, Takashi', 'Matsumura, Tomio', 'Gildea, Sarah', 'Cullinane, Ann']",Influenza Other Respir Viruses,,,True
71ff6abe3023a4c48fd6e6c54265bce395b88397,PMC,Rhinovirus‐associated pulmonary exacerbations show a lack of FEV (1) improvement in children with cystic fibrosis,http://dx.doi.org/10.1111/irv.12353,PMC4746558,26493783,CC BY,"BACKGROUND: Respiratory viral infections lead to bronchial inflammation in patients with cystic fibrosis, especially during pulmonary exacerbations. The aim of this study was to determine the impact of viral‐associated pulmonary exacerbations in children with cystic fibrosis and failure to improve forced expiratory volume in 1 s (FEV (1)) after an appropriate treatment. METHODS: We lead a pilot study from January 2009 until March 2013. Children with a diagnosis of cystic fibrosis were longitudinally evaluated three times: at baseline (Visit 1), at the diagnosis of pulmonary exacerbation (Visit 2), and after exacerbation treatment (Visit 3). Nasal and bronchial samples were analyzed at each visit with multiplex viral respiratory PCR panel (qualitative detection of 16 viruses). Pulmonary function tests were recorded at each visit, in order to highlight a possible failure to improve them after treatment. Lack of improvement was defined by an increase in FEV (1) less than 5% between Visit 2 and Visit 3. RESULTS: Eighteen children were analyzed in the study. 10 patients failed to improve by more than 5% their FEV (1) between Visit 2 and Visit 3. Rhinovirus infection at Visit 2 or Visit 3 was the only risk factor significantly associated with such a failure (OR, 12; 95% CI, 1·3–111·3), P = 0·03. CONCLUSIONS: Rhinovirus infection seems to play a role in the FEV (1) recovery after pulmonary exacerbation treatment in children with cystic fibrosis. Such an association needs to be confirmed by a large‐scale study because this finding may have important implications for pulmonary exacerbation management.",2016 Mar 29,"['Cousin, Mathias', 'Molinari, Nicolas', 'Foulongne, Vincent', 'Caimmi, Davide', 'Vachier, Isabelle', 'Abely, Michel', 'Chiron, Raphael']",Influenza Other Respir Viruses,,,True
b0bb72323af0b1a945243ed46769e00f6d9ceca2,PMC,"Survey of influenza and other respiratory viruses diagnostic testing in US hospitals, 2012–2013",http://dx.doi.org/10.1111/irv.12355,PMC4746564,26505742,CC BY,"BACKGROUND: Little is known about laboratory capacity to routinely diagnose influenza and other respiratory viruses at clinical laboratories and hospitals. AIMS: We sought to assess diagnostic practices for influenza and other respiratory virus in a survey of hospitals and laboratories participating in the US Influenza Hospitalization Surveillance Network in 2012–2013. MATERIALS AND METHODS: All hospitals and their associated laboratories participating in the Influenza Hospitalization Surveillance Network (FluSurv‐NET) were included in this evaluation. The network covers more than 80 counties in 15 states, CA, CO, CT, GA, MD, MN, NM, NY, OR, TN, IA, MI, OH, RI, and UT, with a catchment population of ~28 million people. We administered a standardized questionnaire to key personnel, including infection control practitioners and laboratory departments, at each hospital through telephone interviews. RESULTS: Of the 240 participating laboratories, 67% relied only on commercially available rapid influenza diagnostic tests to diagnose influenza. Few reported the availability of molecular diagnostic assays for detection of influenza (26%) and other viral pathogens (≤20%) in hospitals and commercial laboratories. CONCLUSION: Reliance on insensitive assays to detect influenza may detract from optimal clinical management of influenza infections in hospitals.",2016 Mar 29,"['Su, Su', 'Fry, Alicia M.', 'Kirley, Pam Daily', 'Aragon, Deborah', 'Yousey‐Hindes, Kimberly', 'Meek, James', 'Openo, Kyle', 'Oni, Oluwakemi', 'Sharangpani, Ruta', 'Morin, Craig', 'Hollick, Gary', 'Lung, Krista', 'Laidler, Matt', 'Lindegren, Mary Lou', 'Schaffner, William', 'Atkinson, Annette', 'Chaves, Sandra S.']",Influenza Other Respir Viruses,,,True
80eae3b5b1d0ba7f1806d637628b15ae10e342c4,PMC,"Influenza hospitalization epidemiology from a severe acute respiratory infection surveillance system in Jordan, January 2008–February 2014",http://dx.doi.org/10.1111/irv.12354,PMC4746565,26505620,CC BY,"BACKGROUND: Acute respiratory infections (ARIs) are a major cause of morbidity and mortality worldwide. Influenza typically contributes substantially to the burden of ARI, but only limited data are available on influenza activity and seasonality in Jordan. METHODS: Syndromic case definitions were used to identify individuals with severe acute respiratory infections (SARI) admitted to four sentinel hospitals in Jordan. Demographic and clinical data were collected. Nasopharyngeal and oropharyngeal swabs were tested for influenza using real‐time reverse transcription polymerase chain reaction and typed as influenza A or B, with influenza A further subtyped. RESULTS: From January 2008–February 2014, 2891 SARI cases were tested for influenza, and 257 (9%) were positive. While 73% of all SARI cases were under 5 years of age, only 57% of influenza‐positive cases were under 5 years of age. Eight (3%) influenza‐positive cases died. An annual seasonal pattern of influenza activity was observed. The proportion of influenza‐positive cases peaked during November–January (14–42%) in the non‐pandemic years. CONCLUSIONS: Influenza is associated with substantial morbidity and mortality in Jordan. The seasonal pattern of influenza aligns with known Northern Hemisphere seasonality. Further characterization of the clinical and financial burden of influenza in Jordan will be critical in supporting decisions regarding disease control activities.",2016 Mar 29,"['Al‐Abdallat, Mohammad', 'Dawson, Patrick', 'Haddadin, Aktham Jeries', 'El‐Shoubary, Waleed', 'Dueger, Erica', 'Al‐Sanouri, Tarek', 'Said, Mayar M.', 'Talaat, Maha']",Influenza Other Respir Viruses,,,True
e53bab2c782aab7911dc57e4ecf3759a1755fb21,PMC,Porcine aminopeptidase N binds to F4(+) enterotoxigenic Escherichia coli fimbriae,http://dx.doi.org/10.1186/s13567-016-0313-5,PMC4746772,26857562,CC BY,"F4(+) enterotoxigenic Escherichia coli (ETEC) strains cause diarrheal disease in neonatal and post-weaned piglets. Several different host receptors for F4 fimbriae have been described, with porcine aminopeptidase N (APN) reported most recently. The FaeG subunit is essential for the binding of the three F4 variants to host cells. Here we show in both yeast two-hybrid and pulldown assays that APN binds directly to FaeG, the major subunit of F4 fimbriae, from three serotypes of F4(+) ETEC. Modulating APN gene expression in IPEC-J2 cells affected ETEC adherence. Antibodies raised against APN or F4 fimbriae both reduced ETEC adherence. Thus, APN mediates the attachment of F4(+)E. coli to intestinal epithelial cells.",2016 Feb 9,"['Xia, Pengpeng', 'Wang, Yiting', 'Zhu, Congrui', 'Zou, Yajie', 'Yang, Ying', 'Liu, Wei', 'Hardwidge, Philip R.', 'Zhu, Guoqiang']",Vet Res,,,True
ba619ea88290fb57c91eaa57424ff64b0e811f0b,PMC,Identification of Novel Immunogenic Proteins of Neisseria gonorrhoeae by Phage Display,http://dx.doi.org/10.1371/journal.pone.0148986,PMC4747489,26859666,CC BY,"Neisseria gonorrhoeae is one of the most prevalent sexually transmitted diseases worldwide with more than 100 million new infections per year. A lack of intense research over the last decades and increasing resistances to the recommended antibiotics call for a better understanding of gonococcal infection, fast diagnostics and therapeutic measures against N. gonorrhoeae. Therefore, the aim of this work was to identify novel immunogenic proteins as a first step to advance those unresolved problems. For the identification of immunogenic proteins, pHORF oligopeptide phage display libraries of the entire N. gonorrhoeae genome were constructed. Several immunogenic oligopeptides were identified using polyclonal rabbit antibodies against N. gonorrhoeae. Corresponding full-length proteins of the identified oligopeptides were expressed and their immunogenic character was verified by ELISA. The immunogenic character of six proteins was identified for the first time. Additional 13 proteins were verified as immunogenic proteins in N. gonorrhoeae.",2016 Feb 9,"['Connor, Daniel O.', 'Zantow, Jonas', 'Hust, Michael', 'Bier, Frank F.', 'von Nickisch-Rosenegk, Markus']",PLoS One,,,True
8aca747989e024abacecae2fcc95186972c3f5df,PMC,"A herbal formula comprising Rosae Multiflorae Fructus and Lonicerae Japonicae Flos, attenuates collagen-induced arthritis and inhibits TLR4 signalling in rats",http://dx.doi.org/10.1038/srep20042,PMC4748217,26860973,CC BY,"RL, a traditional remedy for Rheumatoid arthritis (RA), comprises two edible herbs, Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. We have reported that RL could inhibit the production of inflammatory mediators in immune cells. Here we investigated the effects and the mechanism of action of RL in collagen-induced arthritis (CIA) rats. RL significantly increased food intake and weight gain of CIA rats without any observable adverse effect; ameliorated joint erythema and swelling; inhibited immune cell infiltration, bone erosion and osteophyte formation in joints; reduced joint protein expression levels of TLR4, phospho-TAK1, phospho-NF-κB p65, phospho-c-Jun and phospho-IRF3; lowered levels of inflammatory factors (TNF-α, IL-6, IL-1β, IL-17A and MCP-1 in sera and TNF-α, IL-6, IL-1β and IL-17A in joints); elevated serum IL-10 level; reinvigorated activities of antioxidant SOD, CAT and GSH-Px in the liver and serum; reduced Th17 cell proportions in splenocytes; inhibited splenocyte proliferation and activation; and lowered serum IgG level. In conclusion, RL at nontoxic doses inhibited TLR4 signaling and potently improved clinical conditions of CIA rats. These findings provide further pharmacological justifications for the traditional use of RL in RA management.",2016 Feb 10,"['Cheng, Brian Chi Yan', 'Yu, Hua', 'Guo, Hui', 'Su, Tao', 'Fu, Xiu-Qiong', 'Li, Ting', 'Cao, Hui-Hui', 'Tse, Anfernee Kai-Wing', 'Wu, Zheng-Zhi', 'Kwan, Hiu-Yee', 'Yu, Zhi-Ling']",Sci Rep,,,True
93799d2647098d29259b8276c712400ccc96f52d,PMC,"A herbal formula comprising Rosae Multiflorae Fructus and Lonicerae Japonicae Flos, attenuates collagen-induced arthritis and inhibits TLR4 signalling in rats",http://dx.doi.org/10.1038/srep20042,PMC4748217,26860973,CC BY,"RL, a traditional remedy for Rheumatoid arthritis (RA), comprises two edible herbs, Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. We have reported that RL could inhibit the production of inflammatory mediators in immune cells. Here we investigated the effects and the mechanism of action of RL in collagen-induced arthritis (CIA) rats. RL significantly increased food intake and weight gain of CIA rats without any observable adverse effect; ameliorated joint erythema and swelling; inhibited immune cell infiltration, bone erosion and osteophyte formation in joints; reduced joint protein expression levels of TLR4, phospho-TAK1, phospho-NF-κB p65, phospho-c-Jun and phospho-IRF3; lowered levels of inflammatory factors (TNF-α, IL-6, IL-1β, IL-17A and MCP-1 in sera and TNF-α, IL-6, IL-1β and IL-17A in joints); elevated serum IL-10 level; reinvigorated activities of antioxidant SOD, CAT and GSH-Px in the liver and serum; reduced Th17 cell proportions in splenocytes; inhibited splenocyte proliferation and activation; and lowered serum IgG level. In conclusion, RL at nontoxic doses inhibited TLR4 signaling and potently improved clinical conditions of CIA rats. These findings provide further pharmacological justifications for the traditional use of RL in RA management.",2016 Feb 10,"['Cheng, Brian Chi Yan', 'Yu, Hua', 'Guo, Hui', 'Su, Tao', 'Fu, Xiu-Qiong', 'Li, Ting', 'Cao, Hui-Hui', 'Tse, Anfernee Kai-Wing', 'Wu, Zheng-Zhi', 'Kwan, Hiu-Yee', 'Yu, Zhi-Ling']",Sci Rep,,,False
02fdaf97dd0af539eada2af2f1563e0d77a28f92,PMC,Discovery of an antibody for pan-ebolavirus therapy,http://dx.doi.org/10.1038/srep20514,PMC4748290,26861827,CC BY,"During the latest outbreak of Ebola virus disease in West Africa, monoclonal antibody therapy (e.g., ZMapp) was utilized to treat patients. However, due to the antigenic differences among the five ebolavirus species, the current therapeutic monoclonal antibodies are only effective against viruses of the species Zaire ebolavirus. Although this particular species has indeed caused the majority of human infections in Central and, recently, West Africa, other ebolavirus species (e.g., Sudan ebolavirus and Bundibugyo ebolavirus) have also repeatedly caused outbreaks in Central Africa and thus should not be neglected in the development of countermeasures against ebolaviruses. Here we report the generation of an ebolavirus glycoprotein-specific monoclonal antibody that effectively inhibits cellular entry of representative isolates of all known ebolavirus species in vitro and show its protective efficacy in mouse models of ebolavirus infections. This novel neutralizing monoclonal antibody targets a highly conserved internal fusion loop in the glycoprotein molecule and prevents membrane fusion of the viral envelope with cellular membranes. The discovery of this highly cross-neutralizing antibody provides a promising option for broad-acting ebolavirus antibody therapy and will accelerate the design of improved vaccines that can selectively elicit cross-neutralizing antibodies against multiple species of ebolaviruses.",2016 Feb 10,"['Furuyama, Wakako', 'Marzi, Andrea', 'Nanbo, Asuka', 'Haddock, Elaine', 'Maruyama, Junki', 'Miyamoto, Hiroko', 'Igarashi, Manabu', 'Yoshida, Reiko', 'Noyori, Osamu', 'Feldmann, Heinz', 'Takada, Ayato']",Sci Rep,,,True
3104d61248ed91506ee62681f924aaa10dadeeb9,PMC,Discovery of an antibody for pan-ebolavirus therapy,http://dx.doi.org/10.1038/srep20514,PMC4748290,26861827,CC BY,"During the latest outbreak of Ebola virus disease in West Africa, monoclonal antibody therapy (e.g., ZMapp) was utilized to treat patients. However, due to the antigenic differences among the five ebolavirus species, the current therapeutic monoclonal antibodies are only effective against viruses of the species Zaire ebolavirus. Although this particular species has indeed caused the majority of human infections in Central and, recently, West Africa, other ebolavirus species (e.g., Sudan ebolavirus and Bundibugyo ebolavirus) have also repeatedly caused outbreaks in Central Africa and thus should not be neglected in the development of countermeasures against ebolaviruses. Here we report the generation of an ebolavirus glycoprotein-specific monoclonal antibody that effectively inhibits cellular entry of representative isolates of all known ebolavirus species in vitro and show its protective efficacy in mouse models of ebolavirus infections. This novel neutralizing monoclonal antibody targets a highly conserved internal fusion loop in the glycoprotein molecule and prevents membrane fusion of the viral envelope with cellular membranes. The discovery of this highly cross-neutralizing antibody provides a promising option for broad-acting ebolavirus antibody therapy and will accelerate the design of improved vaccines that can selectively elicit cross-neutralizing antibodies against multiple species of ebolaviruses.",2016 Feb 10,"['Furuyama, Wakako', 'Marzi, Andrea', 'Nanbo, Asuka', 'Haddock, Elaine', 'Maruyama, Junki', 'Miyamoto, Hiroko', 'Igarashi, Manabu', 'Yoshida, Reiko', 'Noyori, Osamu', 'Feldmann, Heinz', 'Takada, Ayato']",Sci Rep,,,False
78b7a343a9ffffc005daf8a962cf9140f5dc8735,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,True
24098f1320cc2ade94c6bb512d218e9a8b17a92b,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
1bf05553a642185d7561c2d602cae4bd27443da1,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
477e78bc4f35cdb3cd15bd47a9979f829229cbff,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
e03e5a66cb1095abb7ef2483c15432e37af0a83b,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
169b53d99f650262ddacb0691963b12a419ac24e,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
943d67d2e03c02ac4a13788b20118c92dcc857c0,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
cfa45bbe73a1ed62f2c8d5194881b6a496b2d0c6,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
eefce93d155f312462a786767c8bd6e443685420,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
87b38b6d3186810ad00909c0e2f963214808e4be,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
598afbc9be3b81a14195c3a45e3a4ca580e4958f,PMC,The Hepatitis C Virus-Induced Membranous Web and Associated Nuclear Transport Machinery Limit Access of Pattern Recognition Receptors to Viral Replication Sites,http://dx.doi.org/10.1371/journal.ppat.1005428,PMC4749181,26863439,CC BY,"Hepatitis C virus (HCV) is a positive-strand RNA virus of the Flaviviridae family and a major cause of liver disease worldwide. HCV replicates in the cytoplasm, and the synthesis of viral proteins induces extensive rearrangements of host cell membranes producing structures, collectively termed the membranous web (MW). The MW contains the sites of viral replication and assembly, and we have identified distinct membrane fractions derived from HCV-infected cells that contain replication and assembly complexes enriched for viral RNA and infectious virus, respectively. The complex membrane structure of the MW is thought to protect the viral genome limiting its interactions with cytoplasmic pattern recognition receptors (PRRs) and thereby preventing activation of cellular innate immune responses. Here we show that PRRs, including RIG-I and MDA5, and ribosomes are excluded from viral replication and assembly centers within the MW. Furthermore, we present evidence that components of the nuclear transport machinery regulate access of proteins to MW compartments. We show that the restricted assess of RIG-I to the MW can be overcome by the addition of a nuclear localization signal sequence, and that expression of a NLS-RIG-I construct leads to increased immune activation and the inhibition of viral replication.",2016 Feb 10,"['Neufeldt, Christopher J.', 'Joyce, Michael A.', 'Van Buuren, Nicholas', 'Levin, Aviad', 'Kirkegaard, Karla', 'Gale Jr., Michael', 'Tyrrell, D. Lorne J.', 'Wozniak, Richard W.']",PLoS Pathog,,,True
aa6297e7fd55345b1ef69a2cbbb9629d155580a4,PMC,Development and virucidal activity of a novel alcohol-based hand disinfectant supplemented with urea and citric acid,http://dx.doi.org/10.1186/s12879-016-1410-9,PMC4750209,26864562,CC BY,"BACKGROUND: Hand disinfectants are important for the prevention of virus transmission in the health care system and environment. The development of broad antiviral spectrum hand disinfectants with activity against enveloped and non-enveloped viruses is limited due to a small number of permissible active ingredients able to inactivate viruses. METHODS: A new hand disinfectant was developed based upon 69.39 % w/w ethanol and 3.69 % w/w 2-propanol. Different amounts of citric acid and urea were added in order to create a virucidal claim against poliovirus (PV), adenovirus type 5 (AdV) and polyomavirus SV40 (SV40) as non-enveloped test viruses in the presence of fetal calf serum (FCS) as soil load. The exposure time was fixed to 60 s. RESULTS: With the addition of 2.0 % citric acid and 2.0 % urea an activity against the three test viruses was achieved demonstrating a four log(10) reduction of viral titers. Furthermore, this formulation was able to inactivate PV, AdV, SV40 and murine norovirus (MNV) in quantitative suspension assays according to German and European Guidelines within 60 s creating a virucidal claim. For inactivation of vaccinia virus and bovine viral diarrhea virus 15 s exposure time were needed to demonstrate a 4 log(10) reduction resulting in a claim against enveloped viruses. Additionally, it is the first hand disinfectant passing a carrier test with AdV and MNV. CONCLUSIONS: In conclusion, this new formulation with a low alcohol content, citric acid and urea is capable of inactivating all enveloped and non-enveloped viruses as indicated in current guidelines and thereby contributing as valuable addition to the hand disinfection portfolio.",2016 Feb 11,"['Ionidis, Georgios', 'Hübscher, Judith', 'Jack, Thomas', 'Becker, Britta', 'Bischoff, Birte', 'Todt, Daniel', 'Hodasa, Veronika', 'Brill, Florian H. H.', 'Steinmann, Eike', 'Steinmann, Jochen']",BMC Infect Dis,,,True
e3c22f7e1409db69c1be9a7ae76319405506aaea,PMC,Explaining the geographic spread of emerging epidemics: a framework for comparing viral phylogenies and environmental landscape data,http://dx.doi.org/10.1186/s12859-016-0924-x,PMC4750353,26864798,CC BY,"BACKGROUND: Phylogenetic analysis is now an important tool in the study of viral outbreaks. It can reconstruct epidemic history when surveillance epidemiology data are sparse, and can indicate transmission linkages among infections that may not otherwise be evident. However, a remaining challenge is to develop an analytical framework that can test hypotheses about the effect of environmental variables on pathogen spatial spread. Recent phylogeographic approaches can reconstruct the history of virus dispersal from sampled viral genomes and infer the locations of ancestral infections. Such methods provide a unique source of spatio-temporal information, and are exploited here. RESULTS: We present and apply a new statistical framework that combines genomic and geographic data to test the impact of environmental variables on the mode and tempo of pathogen dispersal during emerging epidemics. First, the spatial history of an emerging pathogen is estimated using standard phylogeographic methods. The inferred dispersal path for each phylogenetic lineage is then assigned a “weight” using environmental data (e.g. altitude, land cover). Next, tests measure the association between each environmental variable and lineage movement. A randomisation procedure is used to assess statistical confidence and we validate this approach using simulated data. We apply our new framework to a set of gene sequences from an epidemic of rabies virus in North American raccoons. We test the impact of six different environmental variables on this epidemic and demonstrate that elevation is associated with a slower rabies spread in a natural population. CONCLUSION: This study shows that it is possible to integrate genomic and environmental data in order to test hypotheses concerning the mode and tempo of virus dispersal during emerging epidemics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-016-0924-x) contains supplementary material, which is available to authorized users.",2016 Feb 11,"['Dellicour, Simon', 'Rose, Rebecca', 'Pybus, Oliver G.']",BMC Bioinformatics,,,True
dce4b37c7dd77b761ad89d62448183f4250d7266,PMC,Optimizing Viral Discovery in Bats,http://dx.doi.org/10.1371/journal.pone.0149237,PMC4750870,26867024,CC BY,"Viral discovery studies in bats have increased dramatically over the past decade, yet a rigorous synthesis of the published data is lacking. We extract and analyze data from 93 studies published between 2007–2013 to examine factors that increase success of viral discovery in bats, and specific trends and patterns of infection across host taxa and viral families. Over the study period, 248 novel viruses from 24 viral families have been described. Using generalized linear models, at a study level we show the number of host species and viral families tested best explained number of viruses detected. We demonstrate that prevalence varies significantly across viral family, specimen type, and host taxonomy, and calculate mean PCR prevalence by viral family and specimen type across all studies. Using a logistic model, we additionally identify factors most likely to increase viral detection at an individual level for the entire dataset and by viral families with sufficient sample sizes. Our analysis highlights major taxonomic gaps in recent bat viral discovery efforts and identifies ways to improve future viral pathogen detection through the design of more efficient and targeted sample collection and screening approaches.",2016 Feb 11,"['Young, Cristin C. W.', 'Olival, Kevin J.']",PLoS One,,,True
05257a2230897ea006b3f68dbf0d71e1e7216f55,PMC,"Long-Term Shedding of Influenza Virus, Parainfluenza Virus, Respiratory Syncytial Virus and Nosocomial Epidemiology in Patients with Hematological Disorders",http://dx.doi.org/10.1371/journal.pone.0148258,PMC4750950,26866481,CC BY,"Respiratory viruses are a cause of upper respiratory tract infections (URTI), but can be associated with severe lower respiratory tract infections (LRTI) in immunocompromised patients. The objective of this study was to investigate the genetic variability of influenza virus, parainfluenza virus and respiratory syncytial virus (RSV) and the duration of viral shedding in hematological patients. Nasopharyngeal swabs from hematological patients were screened for influenza, parainfluenza and RSV on admission as well as on development of respiratory symptoms. Consecutive swabs were collected until viral clearance. Out of 672 tested patients, a total of 111 patients (17%) were infected with one of the investigated viral agents: 40 with influenza, 13 with parainfluenza and 64 with RSV; six patients had influenza/RSV or parainfluenza/RSV co-infections. The majority of infected patients (n = 75/111) underwent stem cell transplantation (42 autologous, 48 allogeneic, 15 autologous and allogeneic). LRTI was observed in 48 patients, of whom 15 patients developed severe LRTI, and 13 patients with respiratory tract infection died. Phylogenetic analysis revealed a variety of influenza A(H1N1)pdm09, A(H3N2), influenza B, parainfluenza 3 and RSV A, B viruses. RSV A was detected in 54 patients, RSV B in ten patients. The newly emerging RSV A genotype ON1 predominated in the study cohort and was found in 48 (75%) of 64 RSV-infected patients. Furthermore, two distinct clusters were detected for RSV A genotype ON1, identical RSV G gene sequences in these patients are consistent with nosocomial transmission. Long-term viral shedding for more than 30 days was significantly associated with prior allogeneic transplantation (p = 0.01) and was most pronounced in patients with RSV infection (n = 16) with a median duration of viral shedding for 80 days (range 35–334 days). Long-term shedding of respiratory viruses might be a catalyzer of nosocomial transmission and must be considered for efficient infection control in immunocompromised patients.",2016 Feb 11,"['Lehners, Nicola', 'Tabatabai, Julia', 'Prifert, Christiane', 'Wedde, Marianne', 'Puthenparambil, Joe', 'Weissbrich, Benedikt', 'Biere, Barbara', 'Schweiger, Brunhilde', 'Egerer, Gerlinde', 'Schnitzler, Paul']",PLoS One,,,True
08b862f9103eb1590d60bd0312f750729b3f2c7d,PMC,Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection,http://dx.doi.org/10.1371/journal.pone.0146599,PMC4752219,26872131,CC BY,"BACKGROUND: The risk of bacteremia is considered low in children with acute bronchiolitis. However the rate of occult bacteremia in infants with RSV infection is not well established. The aim was to determine the actual rate and predictive factors of bacteremia in children admitted to hospital due to confirmed RSV acute respiratory illness (ARI), using both conventional culture and molecular techniques. METHODS: A prospective multicenter study (GENDRES-network) was conducted between 2011–2013 in children under the age of two admitted to hospital because of an ARI. Among those RSV-positive, bacterial presence in blood was assessed using PCR for Meningococcus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, in addition to conventional cultures. RESULTS: 66 children with positive RSV respiratory illness were included. In 10.6% patients, bacterial presence was detected: H. influenzae (n = 4) and S. pneumoniae (n = 2). In those patients with bacteremia, there was a previous suspicion of bacterial superinfection and had received empirical antibiotic treatment 6 out of 7 (85.7%) patients. There were significant differences in terms of severity between children with positive bacterial PCR and those with negative results: PICU admission (100% vs. 50%, P-value = 0.015); respiratory support necessity (100% vs. 18.6%, P-value < 0.001); Wood-Downes score (mean = 8.7 vs. 4.8 points, P-value < 0.001); GENVIP scale (mean = 17 vs. 10.1, P-value < 0.001); and length of hospitalization (mean = 12.1 vs. 7.5 days, P-value = 0.007). CONCLUSION: Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe cases.",2016 Feb 12,"['Cebey-López, Miriam', 'Pardo-Seco, Jacobo', 'Gómez-Carballa, Alberto', 'Martinón-Torres, Nazareth', 'Martinón-Sánchez, José María', 'Justicia-Grande, Antonio', 'Rivero-Calle, Irene', 'Pinnock, Elli', 'Salas, Antonio', 'Fink, Colin', 'Martinón-Torres, Federico', None]",PLoS One,,,True
743035cdbb5b95039bcf2297eecef6e2de640946,PMC,A Rapid and Low-Cost PCR Thermal Cycler for Infectious Disease Diagnostics,http://dx.doi.org/10.1371/journal.pone.0149150,PMC4752298,26872358,CC BY,"The ability to make rapid diagnosis of infectious diseases broadly available in a portable, low-cost format would mark a great step forward in global health. Many molecular diagnostic assays are developed based on using thermal cyclers to carry out polymerase chain reaction (PCR) and reverse-transcription PCR for DNA and RNA amplification and detection, respectively. Unfortunately, most commercial thermal cyclers are expensive and need continuous electrical power supply, so they are not suitable for uses in low-resource settings. We have previously reported a low-cost and simple approach to amplify DNA using vacuum insulated stainless steel thermoses food cans, which we have named it thermos thermal cycler or TTC. Here, we describe the use of an improved set up to enable the detection of viral RNA targets by reverse-transcription PCR (RT-PCR), thus expanding the TTC’s ability to identify highly infectious, RNA virus-based diseases in low resource settings. The TTC was successful in demonstrating high-speed and sensitive detection of DNA or RNA targets of sexually transmitted diseases, HIV/AIDS, Ebola hemorrhagic fever, and dengue fever. Our innovative TTC costs less than $200 to build and has a capacity of at least eight tubes. In terms of speed, the TTC’s performance exceeded that of commercial thermal cyclers tested. When coupled with low-cost endpoint detection technologies such as nucleic acid lateral-flow assay or a cell-phone-based fluorescence detector, the TTC will increase the availability of on-site molecular diagnostics in low-resource settings.",2016 Feb 12,"['Chan, Kamfai', 'Wong, Pui-Yan', 'Yu, Peter', 'Hardick, Justin', 'Wong, Kah-Yat', 'Wilson, Scott A.', 'Wu, Tiffany', 'Hui, Zoe', 'Gaydos, Charlotte', 'Wong, Season S.']",PLoS One,,,True
ad60294d191a68f9db374d7ec49f42c2303b3b00,PMC,Hepatitis C Virus Resistance to Carbohydrate-Binding Agents,http://dx.doi.org/10.1371/journal.pone.0149064,PMC4752358,26871442,CC BY,"Carbohydrate binding agents (CBAs), including natural lectins, are more and more considered as broad-spectrum antivirals. These molecules are able to directly inhibit many viruses such as Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Dengue Virus, Ebola Virus or Severe Acute Respiratory Syndrome Coronavirus through binding to envelope protein N-glycans. In the case of HIV, it has been shown that CBAs select for mutant viruses with N-glycosylation site deletions which are more sensitive to neutralizing antibodies. In this study we aimed at evaluating the HCV resistance to CBAs in vitro. HCV was cultivated in the presence of increasing Galanthus nivalis agglutinin (GNA), Cyanovirin-N, Concanavalin-A or Griffithsin concentrations, during more than eight weeks. At the end of lectin exposure, the genome of the isolated strains was sequenced and several potential resistance mutations in the E1E2 envelope glycoproteins were identified. The effect of these mutations on viral fitness as well as on sensitivity to inhibition by lectins, soluble CD81 or the 3/11 neutralizing antibody was assessed. Surprisingly, none of these mutations, alone or in combination, conferred resistance to CBAs. In contrast, we observed that some mutants were more sensitive to 3/11 or CD81-LEL inhibition. Additionally, several mutations were identified in the Core and the non-structural proteins. Thus, our results suggest that in contrast to HIV, HCV resistance to CBAs is not directly conferred by mutations in the envelope protein genes but could occur through an indirect mechanism involving mutations in other viral proteins. Further investigations are needed to completely elucidate the underlying mechanisms.",2016 Feb 12,"['Izquierdo, Laure', 'Oliveira, Catarina', 'Fournier, Carole', 'Descamps, Véronique', 'Morel, Virginie', 'Dubuisson, Jean', 'Brochot, Etienne', 'Francois, Catherine', 'Castelain, Sandrine', 'Duverlie, Gilles', 'Helle, Francois']",PLoS One,,,True
2c2c2d6a805a6ea5cdd4568c9bedeedc705e1043,PMC,Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages,http://dx.doi.org/10.1371/journal.pone.0149050,PMC4752512,26872335,CC BY,"Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions. Its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalysing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. To this end, we studied IRG1 expression in human immune cells under different inflammatory stimuli, such as TNFα and IFNγ, in addition to lipopolysaccharides. Under these conditions, as previously shown in mouse macrophages, IRG1/CAD accumulates in mitochondria. Furthermore, using literature information and transcription factor prediction models, we re-constructed raw gene regulatory networks (GRNs) for IRG1 in mouse and human macrophages. We further implemented a contextualization algorithm that relies on genome-wide gene expression data to infer putative cell type-specific gene regulatory interactions in mouse and human macrophages, which allowed us to predict potential transcriptional regulators of IRG1. Among the computationally identified regulators, siRNA-mediated gene silencing of interferon regulatory factor 1 (IRF1) in macrophages significantly decreased the expression of IRG1/CAD at the gene and protein level, which correlated with a reduced production of itaconic acid. Using a synergistic approach of both computational and experimental methods, we here shed more light on the transcriptional machinery of IRG1 expression and could pave the way to therapeutic approaches targeting itaconic acid levels.",2016 Feb 12,"['Tallam, Aravind', 'Perumal, Thaneer M.', 'Antony, Paul M.', 'Jäger, Christian', 'Fritz, Joëlle V.', 'Vallar, Laurent', 'Balling, Rudi', 'del Sol, Antonio', 'Michelucci, Alessandro']",PLoS One,,,True
a8c077a7cfb866ed4ad64e152568313e586ca77d,PMC,Dipeptidyl peptidase-4 and kidney fibrosis in diabetes,http://dx.doi.org/10.1186/s13069-016-0038-0,PMC4752740,26877767,CC BY,"Diabetic nephropathy (DN) is the most common cause of end-stage kidney disease worldwide and is associated with increased morbidity and mortality in patients with both type 1 and type 2 diabetes. Recent evidence revealed that dipeptidyl peptidase-4 (DPP-4) inhibitors may exhibit a protective effect against DN. In fact, the kidney is the organ where the DPP-4 activity is the highest level per organ weight. A preclinical analysis revealed that DPP-4 inhibitors also ameliorated kidney fibrosis. In this review, we analyzed recent reports in this field and explore the renoprotective effects and possible mechanism of the DPP-4 inhibitors.",2016 Feb 13,"['Shi, Sen', 'Koya, Daisuke', 'Kanasaki, Keizo']",Fibrogenesis Tissue Repair,,,True
51e85d19c2cec68dfff68624118086ec2bb6de73,PMC,Scientific Collaborations: How Do We Measure the Return on Relationships?,http://dx.doi.org/10.3389/fpubh.2016.00009,PMC4753292,26913278,CC BY,"Emerging infectious diseases (EIDs), the majority of which are zoonotic, represent a tremendous challenge for public health and biosurveillance infrastructure across the globe. Due to the complexity of zoonotic pathogens, it is essential that research and response to EIDs be a transdisciplinary effort. And while crisis and circumstance may be the initial catalyst for responding to an outbreak, we provide examples of how transdisciplinary scientific collectives, which are organized and solidified in advance of crises, can transform the way the world responds to outbreaks and in some cases could even prevent one from occurring (1). Current methods for assessing whether a cooperative engagement between countries is producing measurable and sustainable value is based on the ideas of return on investment and do not consider the inherent importance of relationships. In this article, we apply the idea of return on relationships (ROR) and propose a method for measuring ROR, using a system dynamics modeling framework commonly used in epidemiology. Tracking the numerous and diverse scientific collaborations that emerged from a training workshop for biosurveillance of bats held in Singapore in 2014, we apply a methodology for visualizing and measuring the relationship networks and outcomes that result. Additionally, the collaborative, multidisciplinary network that coalesced in response to the Hantavirus outbreak in New Mexico is 1993 is discussed as an example of the long-term benefits of ROR.",2016 Feb 15,"['Fair, Jeanne M.', 'Stokes, Martha Mangum', 'Pennington, Deana', 'Mendenhall, Ian H.']",Front Public Health,,,True
5f7b5b1f4748ede29130df5606fd51f4820edc20,PMC,Conformational Flexibility of a Short Loop near the Active Site of the SARS-3CLpro is Essential to Maintain Catalytic Activity,http://dx.doi.org/10.1038/srep20918,PMC4754693,26879383,CC BY,"The SARS 3C-like proteinase (SARS-3CLpro), which is the main proteinase of the SARS coronavirus, is essential to the virus life cycle. This enzyme has been shown to be active as a dimer in which only one protomer is active. However, it remains unknown how the dimer structure maintains an active monomer conformation. It has been observed that the Ser139-Leu141 loop forms a short 3(10)-helix that disrupts the catalytic machinery in the inactive monomer structure. We have tried to disrupt this helical conformation by mutating L141 to T in the stable inactive monomer G11A/R298A/Q299A. The resulting tetra-mutant G11A/L141T/R298A/Q299A is indeed enzymatically active as a monomer. Molecular dynamics simulations revealed that the L141T mutation disrupts the 3(10)-helix and helps to stabilize the active conformation. The coil-3(10)-helix conformational transition of the Ser139-Leu141 loop serves as an enzyme activity switch. Our study therefore indicates that the dimer structure can stabilize the active conformation but is not a required structure in the evolution of the active enzyme, which can also arise through simple mutations.",2016 Feb 16,"['Li, Chunmei', 'Teng, Xin', 'Qi, Yifei', 'Tang, Bo', 'Shi, Hailing', 'Ma, Xiaomin', 'Lai, Luhua']",Sci Rep,,,True
95f0f21246953b8b6258cdf4afd61011c32a686f,PMC,Niclosamide inhibits leaf blight caused by Xanthomonas oryzae in rice,http://dx.doi.org/10.1038/srep21209,PMC4754756,26879887,CC BY,"Rice leaf blight, which is caused by the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo), results in huge losses in grain yield. Here, we show that Xoo-induced rice leaf blight is effectively controlled by niclosamide, an oral antihelminthic drug and molluscicide, which also functions as an anti-tumor agent. Niclosamide directly inhibited the growth of the three Xoo strains PXO99, 10208 and K3a. Niclosamide moved long distances from the site of local application to distant rice tissues. Niclosamide also increased the levels of salicylate and induced the expression of defense-related genes such as OsPR1 and OsWRKY45, which suppressed Xoo-induced leaf wilting. Niclosamide had no detrimental effects on vegetative/reproductive growth and yield. These combined results indicate that niclosamide can be used to block bacterial leaf blight in rice with no negative side effects.",2016 Feb 16,"['Kim, Sung-Il', 'Song, Jong Tae', 'Jeong, Jin-Yong', 'Seo, Hak Soo']",Sci Rep,,,True
7dad7185f2f7dd28cfaa251822682e46bb5b26e6,PMC,"Fugong virus, a novel hantavirus harbored by the small oriental vole (Eothenomys eleusis) in China",http://dx.doi.org/10.1186/s12985-016-0483-9,PMC4754816,26880191,CC BY,"BACKGROUND: Rodents are natural reservoirs of hantaviruses, which cause two disease types: hemorrhagic fever with renal syndrome in Eurasia and hantavirus pulmonary syndrome in North America. Hantaviruses related human cases have been observed throughout Asia, Europe, Africa, and North America. To date, 23 distinct species of hantaviruses, hosted by reservoir, have been identified. However, the diversity and number of hantaviruses are likely underestimated in China, and hantavirus species that cause disease in many regions, including Yunnan province, are unknown. RESULTS: In August 2012, we collected tissue samples from 189 captured animals, including 15 species belonging to 10 genera, 5 families, and 4 orders in Fugong county, Yunnan province, China. Seven species were positive for hantavirus: Eothenomys eleusis (42/94), Apodemus peninsulae (3/25), Niviventer eha (3/27), Cryptotis montivaga (2/8), Anourosorex squamipes (1/1), Sorex araneus (1/1), and Mustela sibirica (1/2). We characterized one full-length genomic sequence of the virus (named fugong virus, FUGV) from a small oriental vole (Eothenomys eleusis). The full-length sequences of the small, medium, and large segments of FUGV were 1813, 3630, and 6531 nt, respectively. FUGV was most closely related to hantavirus LX309, a previously reported species detected in the red-backed vole in Luxi county, Yunnan province, China. However, the amino acid sequences of nucleocapsid (N), glycoprotein (G), and large protein (L) were highly divergent from those of Hantavirus LX309, with amino acid differences of 11.2, 15.3, and 12.7 %, respectively. In phylogenetic trees, FUGV clustered in the lineage corresponding to hantaviruses carried by rodents in the subfamily Arvicolinae. CONCLUSIONS: High prevalence of hantavirus infection in small mammals was found in Fugong county, Yunnan province, China. A novel hantavirus species FUGV was identified from the small oriental vole. This virus is phylogenetic clustering with another hantavirus LX309, but shows highly genomic divergence.",2016 Feb 16,"['Ge, Xing-Yi', 'Yang, Wei-Hong', 'Pan, Hong', 'Zhou, Ji-Hua', 'Han, Xi', 'Zhu, Guang-Jian', 'Desmond, James S.', 'Daszak, Peter', 'Shi, Zheng-Li', 'Zhang, Yun-Zhi']",Virol J,,,True
8e3f518b27782ac9cc19e7556d74100ff23d972b,PMC,Porcine parvovirus infection activates mitochondria-mediated apoptotic signaling pathway by inducing ROS accumulation,http://dx.doi.org/10.1186/s12985-016-0480-z,PMC4755023,26880103,CC BY,"BACKGROUND: Porcine parvovirus (PPV) infection primarily causes reproductive failure of pregnant swine and results in host cell death. Boars, as an important disseminator, shed PPV to sows via semen. PPV infects and numerously replicates in boar testicle, which results in damage of swine testicle in vivo. Reactive oxygen species (ROS), a mediator of cell apoptosis, play a crucial role in the mitochondria apoptotic pathway. However, whether PPV infection induces ST cells apoptosis and ROS accumulation is still unclear. METHODS: To determine the effects of PPV infection on the apoptosis, we detected morphological changes, DNA ladder, activities of caspases, and expression of PARP in PPV-infected ST cells. Moreover, aiming to investigate the effect of PPV infection on the mitochondrial apoptotic pathway and ROS accumulation, we detected the Δψm, apoptosis-related genes, and ROS. To investigate the role of ROS in the process of PPV-induced apoptosis, the ST cells were infected with PPV and treated with the ROS antioxidants. The ROS level was measured using Reactive Oxygen Species Assay Kit and the Δψm, expression level of Bcl-2, translocation of Bax, and redistribution of mitochondria cytochrome c were tested. RESULTS: In this study, we demonstrated that PPV infection could induce apoptosis that was characterized by morphological changes, DNA fragmentation and activation of caspases. Moreover, PPV infection suppressed Bcl-2 expression, enhanced Bax expression and translocation to mitochondria, decreased the mitochondrial transmembrane potential, and triggered the release of cytochrome c, which caused the subsequent activation of caspase-9 and caspase-3 and initiation of apoptosis. However, during the process of PPV-induced apoptosis, the protein levels of Fas and FasL were not affected. Further studies showed that PPV infection caused ROS accumulation. Inhibition of ROS could reduce mitochondrial transmembrane potential and could significantly block ST cells apoptosis via suppressing Bax translocation, cytochrome c and caspase-3 activation. CONCLUSIONS: All these results suggest that PPV-induced ROS accumulation mediates apoptosis in ST cells, which provided theoretical basis for the molecular pathogenesis of PPV infection.",2016 Feb 16,"['Zhao, Xiaomin', 'Xiang, Hailing', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Song, Xiangjun', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",Virol J,,,True
38bed8a14f2f6103cf5f8ddc6db772c8ab52f7c4,PMC,Pathogenesis and Diagnostic Approaches of Avian Infectious Bronchitis,http://dx.doi.org/10.1155/2016/4621659,PMC4756178,26955391,CC BY,"Infectious bronchitis (IB) is one of the major economically important poultry diseases distributed worldwide. It is caused by infectious bronchitis virus (IBV) and affects both galliform and nongalliform birds. Its economic impact includes decreased egg production and poor egg quality in layers, stunted growth, poor carcass weight, and mortality in broiler chickens. Although primarily affecting the respiratory tract, IBV demonstrates a wide range of tissues tropism, including the renal and reproductive systems. Thus, disease outcome may be influenced by the organ or tissue involved as well as pathotypes or strain of the infecting virus. Knowledge on the epidemiology of the prevalent IBV strains in a particular region is therefore important to guide control and preventions. Meanwhile previous diagnostic methods such as serology and virus isolations are less sensitive and time consuming, respectively; current methods, such as reverse transcription polymerase chain reaction (RT-PCR), Restriction Fragment Length Polymorphism (RFLP), and sequencing, offer highly sensitive, rapid, and accurate diagnostic results, thus enabling the genotyping of new viral strains within the shortest possible time. This review discusses aspects on pathogenesis and diagnostic methods for IBV infection.",2016 Feb 3,"['Bande, Faruku', 'Arshad, Siti Suri', 'Omar, Abdul Rahman', 'Bejo, Mohd Hair', 'Abubakar, Muhammad Salisu', 'Abba, Yusuf']",Adv Virol,,,True
4589d4013cf69c396e0fdb67131022fc11119654,PMC,Association between the Severity of Influenza A(H7N9) Virus Infections and Length of the Incubation Period,http://dx.doi.org/10.1371/journal.pone.0148506,PMC4757028,26885816,CC BY,"BACKGROUND: In early 2013, a novel avian-origin influenza A(H7N9) virus emerged in China, and has caused sporadic human infections. The incubation period is the delay from infection until onset of symptoms, and varies from person to person. Few previous studies have examined whether the duration of the incubation period correlates with subsequent disease severity. METHODS AND FINDINGS: We analyzed data of period of exposure on 395 human cases of laboratory-confirmed influenza A(H7N9) virus infection in China in a Bayesian framework using a Weibull distribution. We found a longer incubation period for the 173 fatal cases with a mean of 3.7 days (95% credibility interval, CrI: 3.4–4.1), compared to a mean of 3.3 days (95% CrI: 2.9–3.6) for the 222 non-fatal cases, and the difference in means was marginally significant at 0.47 days (95% CrI: -0.04, 0.99). There was a statistically significant correlation between a longer incubation period and an increased risk of death after adjustment for age, sex, geographical location and underlying medical conditions (adjusted odds ratio 1.70 per day increase in incubation period; 95% credibility interval 1.47–1.97). CONCLUSIONS: We found a significant association between a longer incubation period and a greater risk of death among human H7N9 cases. The underlying biological mechanisms leading to this association deserve further exploration.",2016 Feb 17,"['Virlogeux, Victor', 'Yang, Juan', 'Fang, Vicky J.', 'Feng, Luzhao', 'Tsang, Tim K.', 'Jiang, Hui', 'Wu, Peng', 'Zheng, Jiandong', 'Lau, Eric H. Y.', 'Qin, Ying', 'Peng, Zhibin', 'Peiris, J. S. Malik', 'Yu, Hongjie', 'Cowling, Benjamin J.']",PLoS One,,,True
00326efcca0852dc6e39dc6b7786267e1bc4f194,PMC,"A Review of Pediatric Critical Care in Resource-Limited Settings: A Look at Past, Present, and Future Directions",http://dx.doi.org/10.3389/fped.2016.00005,PMC4757646,26925393,CC BY,"Fifteen years ago, United Nations world leaders defined millenium development goal 4 (MDG 4): to reduce under-5-year mortality rates by two-thirds by the year 2015. Unfortunately, only 27 of 138 developing countries are expected to achieve MDG 4. The majority of childhood deaths in these settings result from reversible causes, and developing effective pediatric emergency and critical care services could substantially reduce this mortality. The Ebola outbreak highlighted the fragility of health care systems in resource-limited settings and emphasized the urgent need for a paradigm shift in the global approach to healthcare delivery related to critical illness. This review provides an overview of pediatric critical care in resource-limited settings and outlines strategies to address challenges specific to these areas. Implementation of these tools has the potential to move us toward delivery of an adequate standard of critical care for all children globally, and ultimately decrease global child mortality in resource-limited settings.",2016 Feb 18,"['Turner, Erin L.', 'Nielsen, Katie R.', 'Jamal, Shelina M.', 'von Saint André-von Arnim, Amelie', 'Musa, Ndidiamaka L.']",Front Pediatr,,,True
77fc830cd32e8b07cd22a11a8d519f9d35f7d7ff,PMC,Effects of memory on the shapes of simple outbreak trees,http://dx.doi.org/10.1038/srep21159,PMC4758066,26888437,CC BY,"Genomic tools, including phylogenetic trees derived from sequence data, are increasingly used to understand outbreaks of infectious diseases. One challenge is to link phylogenetic trees to patterns of transmission. Particularly in bacteria that cause chronic infections, this inference is affected by variable infectious periods and infectivity over time. It is known that non-exponential infectious periods can have substantial effects on pathogens’ transmission dynamics. Here we ask how this non-Markovian nature of an outbreak process affects the branching trees describing that process, with particular focus on tree shapes. We simulate Crump-Mode-Jagers branching processes and compare different patterns of infectivity over time. We find that memory (non-Markovian-ness) in the process can have a pronounced effect on the shapes of the outbreak’s branching pattern. However, memory also has a pronounced effect on the sizes of the trees, even when the duration of the simulation is fixed. When the sizes of the trees are constrained to a constant value, memory in our processes has little direct effect on tree shapes, but can bias inference of the birth rate from trees. We compare simulated branching trees to phylogenetic trees from an outbreak of tuberculosis in Canada, and discuss the relevance of memory to this dataset.",2016 Feb 18,"['Plazzotta, Giacomo', 'Kwan, Christopher', 'Boyd, Michael', 'Colijn, Caroline']",Sci Rep,,,True
4d7b3ed96d9a6f56840f5a3b47aac5fb24999635,PMC,Effects of memory on the shapes of simple outbreak trees,http://dx.doi.org/10.1038/srep21159,PMC4758066,26888437,CC BY,"Genomic tools, including phylogenetic trees derived from sequence data, are increasingly used to understand outbreaks of infectious diseases. One challenge is to link phylogenetic trees to patterns of transmission. Particularly in bacteria that cause chronic infections, this inference is affected by variable infectious periods and infectivity over time. It is known that non-exponential infectious periods can have substantial effects on pathogens’ transmission dynamics. Here we ask how this non-Markovian nature of an outbreak process affects the branching trees describing that process, with particular focus on tree shapes. We simulate Crump-Mode-Jagers branching processes and compare different patterns of infectivity over time. We find that memory (non-Markovian-ness) in the process can have a pronounced effect on the shapes of the outbreak’s branching pattern. However, memory also has a pronounced effect on the sizes of the trees, even when the duration of the simulation is fixed. When the sizes of the trees are constrained to a constant value, memory in our processes has little direct effect on tree shapes, but can bias inference of the birth rate from trees. We compare simulated branching trees to phylogenetic trees from an outbreak of tuberculosis in Canada, and discuss the relevance of memory to this dataset.",2016 Feb 18,"['Plazzotta, Giacomo', 'Kwan, Christopher', 'Boyd, Michael', 'Colijn, Caroline']",Sci Rep,,,False
d54725b7c8072e09a2498c8f2ce1e7ee7839eaf6,PMC,"Complete Genome Sequence of a Porcine Epidemic Diarrhea Virus Strain from Vietnam, HUA-14PED96, with a Large Genomic Deletion",http://dx.doi.org/10.1128/genomeA.00002-16,PMC4759056,26893409,CC BY,"A highly virulent strain of Porcine epidemic diarrhea virus (PEDV) causing severe diarrhea has recently emerged in Vietnam. Genomic sequences from a novel strain, HUA-14PED96, isolated from a Vietnamese piglet with serious diarrhea show relatively high identity with U.S.-like PEDV strains, and have a 72-nt deletion in the open reading frame 1a (ORF1a) gene.",2016 Feb 18,"['Choe, Se-Eun', 'Park, Kee-Hwan', 'Lim, Seong-In', 'Le, Van Phan', 'Hien, Nguyen Ba', 'Thach, Pham Ngoc', 'Phuong, Le Huynh Thanh', 'An, Byung-Hyun', 'Han, Song Hee', 'Cho, In-Soo', 'An, Dong-Jun']",Genome Announc,,,True
882f40d2ce4eceeb438b59e25e2e023fb5e169ba,PMC,"Impact of Influenza on Outpatient Visits, Hospitalizations, and Deaths by Using a Time Series Poisson Generalized Additive Model",http://dx.doi.org/10.1371/journal.pone.0149468,PMC4760679,26894876,CC BY,"BACKGROUND: The disease burden associated with influenza in developing tropical and subtropical countries is poorly understood owing to the lack of a comprehensive disease surveillance system and information-exchange mechanisms. The impact of influenza on outpatient visits, hospital admissions, and deaths has not been fully demonstrated to date in south China. METHODS: A time series Poisson generalized additive model was used to quantitatively assess influenza-like illness (ILI) and influenza disease burden by using influenza surveillance data in Zhuhai City from 2007 to 2009, combined with the outpatient, inpatient, and respiratory disease mortality data of the same period. RESULTS: The influenza activity in Zhuhai City demonstrated a typical subtropical seasonal pattern; however, each influenza virus subtype showed a specific transmission variation. The weekly ILI case number and virus isolation rate had a very close positive correlation (r = 0.774, P < 0.0001). The impact of ILI and influenza on weekly outpatient visits was statistically significant (P < 0.05). We determined that 10.7% of outpatient visits were associated with ILI and 1.88% were associated with influenza. ILI also had a significant influence on the hospitalization rates (P < 0.05), but mainly in populations <25 years of age. No statistically significant effect of influenza on hospital admissions was found (P > 0.05). The impact of ILI on chronic obstructive pulmonary disease (COPD) was most significant (P < 0.05), with 33.1% of COPD-related deaths being attributable to ILI. The impact of influenza on the mortality rate requires further evaluation. CONCLUSIONS: ILI is a feasible indicator of influenza activity. Both ILI and influenza have a large impact on outpatient visits. Although ILI affects the number of hospital admissions and deaths, we found no consistent influence of influenza, which requires further assessment.",2016 Feb 19,"['Guo, Ru-ning', 'Zheng, Hui-zhen', 'Ou, Chun-quan', 'Huang, Li-qun', 'Zhou, Yong', 'Zhang, Xin', 'Liang, Can-kun', 'Lin, Jin-yan', 'Zhong, Hao-jie', 'Song, Tie', 'Luo, Hui-ming']",PLoS One,,,True
4a94f3fe57da5dad4c965d59faf0facc2039175a,PMC,Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines,http://dx.doi.org/10.1371/journal.pone.0149364,PMC4760941,26895072,CC0,"The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification). The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1) elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that MVA and MVA-vectored vaccines inoculated by scarification can elicit protective immune responses that are comparable to subcutaneous vaccination, and may allow for antigen sparing when vaccine supply is limited.",2016 Feb 19,"['Meseda, Clement A.', 'Atukorale, Vajini', 'Kuhn, Jordan', 'Schmeisser, Falko', 'Weir, Jerry P.']",PLoS One,,,True
f3869eb49905ee75dbd6acd2964cb74f69154b2a,PMC,Virus replicon particles expressing porcine reproductive and respiratory syndrome virus proteins elicit immune priming but do not confer protection from viremia in pigs,http://dx.doi.org/10.1186/s13567-016-0318-0,PMC4761149,26895704,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of one of the most devastating and economically significant viral disease of pigs worldwide. The vaccines currently available on the market elicit only limited protection. Recombinant vesicular stomatitis virus (VSV) replicon particles (VRP) have been used successfully to induce protection against influenza A virus (IAV) in chickens and bluetongue virus in sheep. In this study, VSV VRP expressing the PRRSV envelope proteins GP5, M, GP4, GP3, GP2 and the nucleocapsid protein N, individually or in combination, were generated and evaluated as a potential vector vaccine against PRRSV infection. High level expression of the recombinant PRRSV proteins was demonstrated in cell culture. However, none of the PRRSV antigens expressed from VRP, with the exception of the N protein, did induce any detectable antibody response in pigs before challenge infection with PRRSV. After challenge however, the antibody responses against GP5, GP4 and GP3 appeared in average 2 weeks earlier than in pigs vaccinated with the empty control VRP. No reduction of viremia was observed in the vaccinated group compared with the control group. When pigs were co-vaccinated with VRP expressing IAV antigens and VRP expressing PRRSV glycoproteins, only antibody responses to the IAV antigens were detectable. These data show that the VSV replicon vector can induce immune responses to heterologous proteins in pigs, but that the PRRSV envelope proteins expressed from VSV VRP are poorly immunogenic. Nevertheless, they prime the immune system for significantly earlier B-cell responses following PRRSV challenge infection.",2016 Feb 19,"['Eck, Melanie', 'Durán, Margarita García', 'Ricklin, Meret E.', 'Locher, Samira', 'Sarraseca, Javier', 'Rodríguez, María José', 'McCullough, Kenneth C.', 'Summerfield, Artur', 'Zimmer, Gert', 'Ruggli, Nicolas']",Vet Res,,,True
577c6a13f9ef70e9756890fc66e98f537c01ac0a,PMC,Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis),http://dx.doi.org/10.1038/srep21878,PMC4761889,26899616,CC BY,"The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential of Betacoronaviruses. Investigations into the origin of MERS-CoV have focused on two potential reservoirs: bats and camels. Here, we investigated the role of bats as a potential reservoir for MERS-CoV. In vitro, the MERS-CoV spike glycoprotein interacted with Jamaican fruit bat (Artibeus jamaicensis) dipeptidyl peptidase 4 (DPP4) receptor and MERS-CoV replicated efficiently in Jamaican fruit bat cells, suggesting there is no restriction at the receptor or cellular level for MERS-CoV. To shed light on the intrinsic host-virus relationship, we inoculated 10 Jamaican fruit bats with MERS-CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days. MERS-CoV replicated transiently in the respiratory and, to a lesser extent, the intestinal tracts and internal organs; with limited histopathological changes observed only in the lungs. Analysis of the innate gene expression in the lungs showed a moderate, transient induction of expression. Our results indicate that MERS-CoV maintains the ability to replicate in bats without clinical signs of disease, supporting the general hypothesis of bats as ancestral reservoirs for MERS-CoV.",2016 Feb 22,"['Munster, Vincent J.', 'Adney, Danielle R.', 'van Doremalen, Neeltje', 'Brown, Vienna R.', 'Miazgowicz, Kerri L.', 'Milne-Price, Shauna', 'Bushmaker, Trenton', 'Rosenke, Rebecca', 'Scott, Dana', 'Hawkinson, Ann', 'de Wit, Emmie', 'Schountz, Tony', 'Bowen, Richard A.']",Sci Rep,,,True
5e43557663dd87fa5099c9abb009b9a85e3c474f,PMC,Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis),http://dx.doi.org/10.1038/srep21878,PMC4761889,26899616,CC BY,"The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential of Betacoronaviruses. Investigations into the origin of MERS-CoV have focused on two potential reservoirs: bats and camels. Here, we investigated the role of bats as a potential reservoir for MERS-CoV. In vitro, the MERS-CoV spike glycoprotein interacted with Jamaican fruit bat (Artibeus jamaicensis) dipeptidyl peptidase 4 (DPP4) receptor and MERS-CoV replicated efficiently in Jamaican fruit bat cells, suggesting there is no restriction at the receptor or cellular level for MERS-CoV. To shed light on the intrinsic host-virus relationship, we inoculated 10 Jamaican fruit bats with MERS-CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days. MERS-CoV replicated transiently in the respiratory and, to a lesser extent, the intestinal tracts and internal organs; with limited histopathological changes observed only in the lungs. Analysis of the innate gene expression in the lungs showed a moderate, transient induction of expression. Our results indicate that MERS-CoV maintains the ability to replicate in bats without clinical signs of disease, supporting the general hypothesis of bats as ancestral reservoirs for MERS-CoV.",2016 Feb 22,"['Munster, Vincent J.', 'Adney, Danielle R.', 'van Doremalen, Neeltje', 'Brown, Vienna R.', 'Miazgowicz, Kerri L.', 'Milne-Price, Shauna', 'Bushmaker, Trenton', 'Rosenke, Rebecca', 'Scott, Dana', 'Hawkinson, Ann', 'de Wit, Emmie', 'Schountz, Tony', 'Bowen, Richard A.']",Sci Rep,,,False
69129d8f3e4a1c80f2437d16f044e37e43c03f37,PMC,Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses,http://dx.doi.org/10.1038/ncomms10680,PMC4762884,26893169,CC BY,"Stimulator of interferon genes (STING) is known be involved in control of DNA viruses but has an unexplored role in control of RNA viruses. During infection with DNA viruses STING is activated downstream of cGAMP synthase (cGAS) to induce type I interferon. Here we identify a STING-dependent, cGAS-independent pathway important for full interferon production and antiviral control of enveloped RNA viruses, including influenza A virus (IAV). Further, IAV interacts with STING through its conserved hemagglutinin fusion peptide (FP). Interestingly, FP antagonizes interferon production induced by membrane fusion or IAV but not by cGAMP or DNA. Similar to the enveloped RNA viruses, membrane fusion stimulates interferon production in a STING-dependent but cGAS-independent manner. Abolishment of this pathway led to reduced interferon production and impaired control of enveloped RNA viruses. Thus, enveloped RNA viruses stimulate a cGAS-independent STING pathway, which is targeted by IAV.",2016 Feb 19,"['Holm, Christian K.', 'Rahbek, Stine H.', 'Gad, Hans Henrik', 'Bak, Rasmus O.', 'Jakobsen, Martin R.', 'Jiang, Zhaozaho', 'Hansen, Anne Louise', 'Jensen, Simon K.', 'Sun, Chenglong', 'Thomsen, Martin K.', 'Laustsen, Anders', 'Nielsen, Camilla G.', 'Severinsen, Kasper', 'Xiong, Yingluo', 'Burdette, Dara L.', 'Hornung, Veit', 'Lebbink, Robert Jan', 'Duch, Mogens', 'Fitzgerald, Katherine A.', 'Bahrami, Shervin', 'Mikkelsen, Jakob Giehm', 'Hartmann, Rune', 'Paludan, Søren R.']",Nat Commun,,,True
7249caf14f73593c88c505809ebfa9dc24e6dbe0,PMC,Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses,http://dx.doi.org/10.1038/ncomms10680,PMC4762884,26893169,CC BY,"Stimulator of interferon genes (STING) is known be involved in control of DNA viruses but has an unexplored role in control of RNA viruses. During infection with DNA viruses STING is activated downstream of cGAMP synthase (cGAS) to induce type I interferon. Here we identify a STING-dependent, cGAS-independent pathway important for full interferon production and antiviral control of enveloped RNA viruses, including influenza A virus (IAV). Further, IAV interacts with STING through its conserved hemagglutinin fusion peptide (FP). Interestingly, FP antagonizes interferon production induced by membrane fusion or IAV but not by cGAMP or DNA. Similar to the enveloped RNA viruses, membrane fusion stimulates interferon production in a STING-dependent but cGAS-independent manner. Abolishment of this pathway led to reduced interferon production and impaired control of enveloped RNA viruses. Thus, enveloped RNA viruses stimulate a cGAS-independent STING pathway, which is targeted by IAV.",2016 Feb 19,"['Holm, Christian K.', 'Rahbek, Stine H.', 'Gad, Hans Henrik', 'Bak, Rasmus O.', 'Jakobsen, Martin R.', 'Jiang, Zhaozaho', 'Hansen, Anne Louise', 'Jensen, Simon K.', 'Sun, Chenglong', 'Thomsen, Martin K.', 'Laustsen, Anders', 'Nielsen, Camilla G.', 'Severinsen, Kasper', 'Xiong, Yingluo', 'Burdette, Dara L.', 'Hornung, Veit', 'Lebbink, Robert Jan', 'Duch, Mogens', 'Fitzgerald, Katherine A.', 'Bahrami, Shervin', 'Mikkelsen, Jakob Giehm', 'Hartmann, Rune', 'Paludan, Søren R.']",Nat Commun,,,False
ca96f361ba8d99dedbd1421fe735d230e86f7797,PMC,The Glycoproteins of All Filovirus Species Use the Same Host Factors for Entry into Bat and Human Cells but Entry Efficiency Is Species Dependent,http://dx.doi.org/10.1371/journal.pone.0149651,PMC4762945,26901159,CC BY,"Ebola and marburgviruses, members of the family Filoviridae, can cause severe hemorrhagic fever in humans. The ongoing Ebola virus (EBOV) disease epidemic in Western Africa claimed more than 11,300 lives and was associated with secondary cases outside Africa, demonstrating that filoviruses pose a global health threat. Bats constitute an important natural reservoir of filoviruses, including viruses of the recently identified Cuevavirus genus within the Filoviridae family. However, the interactions of filoviruses with bat cells are incompletely understood. Here, we investigated whether filoviruses employ different strategies to enter human and bat cells. For this, we examined host cell entry driven by glycoproteins (GP) from all filovirus species into cell lines of human and fruit bat origin. We show that all GPs were able to mediate entry into human and most fruit bat cell lines with roughly comparable efficiency. In contrast, the efficiency of entry into the cell line EidNi/41 derived from a straw-colored fruit bat varied markedly between the GPs of different filovirus species. Furthermore, inhibition studies demonstrated that filoviruses employ the same host cell factors for entry into human, non-human primate and fruit bat cell lines, including cysteine proteases, two pore channels and NPC1 (Niemann-Pick C1 molecule). Finally, processing of GP by furin and the presence of the mucin-like domain in GP were dispensable for entry into both human and bat cell lines. Collectively, these results show that filoviruses rely on the same host cell factors for entry into human and fruit bat cells, although the efficiency of the usage of these factors might differ between filovirus species.",2016 Feb 22,"['Hoffmann, Markus', 'González Hernández, Mariana', 'Berger, Elisabeth', 'Marzi, Andrea', 'Pöhlmann, Stefan']",PLoS One,,,True
5ea003777403bda990fe5a2471273b477e529751,PMC,Protective effects of fenofibrate against acute lung injury induced by intestinal ischemia/reperfusion in mice,http://dx.doi.org/10.1038/srep22044,PMC4763198,26902261,CC BY,"This experiment was conducted to evaluate whether pretreatment with fenofibrate could mitigate acute lung injury (ALI) in a mice model of intestinal ischemia/reperfusion (I/R). Male C57BL/6 mice were randomly assigned into three groups (n = 6): sham, intestinal I/R + vehicle, and intestinal I/R + fenofibrate. Intestinal I/R was achieved by clamping the superior mesenteric artery. Fenofibrate (100 mg/kg) or equal volume of vehicle was injected intraperitoneally 60 minutes before the ischemia. At the end of experiment, measurement of pathohistological score, inflammatory mediators and other markers were performed. In addition, a 24-hour survival experiment was conducted in intestinal I/R mice treated with fenofibrate or vehicle. The chief results were as anticipated. Pathohistological evaluation indicated that fenofibrate ameliorated the local intestine damage and distant lung injury. Pretreatment with fenofibrate significantly decreased inflammatory factors in both the intestine and the lung. Consistently, renal creatine levels and hepatic ALT levels were significantly decreased in the fenofibrate group. Moreover, serum systemic inflammatory response indicators were significantly alleviated in the fenofibrate group. In addition, fenofibrate administration significantly improved the survival rate. Collectively, our data indicated that pretreatment with fenofibrate prior to ischemia attenuated intestinal I/R injury and ALI.",2016 Feb 23,"['Zhu, Qiankun', 'He, Guizhen', 'Wang, Jie', 'Wang, Yukang', 'Chen, Wei']",Sci Rep,,,True
de0bb38fe24062ae86287891a21a9851a0e6b7f3,PMC,Delayed Time-to-Treatment of an Antisense Morpholino Oligomer Is Effective against Lethal Marburg Virus Infection in Cynomolgus Macaques,http://dx.doi.org/10.1371/journal.pntd.0004456,PMC4764691,26901785,CC0,"Marburg virus (MARV) is an Ebola-like virus in the family Filovirdae that causes sporadic outbreaks of severe hemorrhagic fever with a case fatality rate as high as 90%. AVI-7288, a positively charged antisense phosphorodiamidate morpholino oligomer (PMOplus) targeting the viral nucleoprotein gene, was evaluated as a potential therapeutic intervention for MARV infection following delayed treatment of 1, 24, 48, and 96 h post-infection (PI) in a nonhuman primate lethal challenge model. A total of 30 cynomolgus macaques were divided into 5 groups of 6 and infected with 1,830 plaque forming units of MARV subcutaneously. AVI-7288 was administered by bolus infusion daily for 14 days at 15 mg/kg body weight. Survival was the primary endpoint of the study. While none (0 of 6) of the saline group survived, 83–100% of infected monkeys survived when treatment was initiated 1, 24, 48, or 96 h post-infection (PI). The antisense treatment also reduced serum viremia and inflammatory cytokines in all treatment groups compared to vehicle controls. The antibody immune response to virus was preserved and tissue viral antigen was cleared in AVI-7288 treated animals. These data show that AVI-7288 protects NHPs against an otherwise lethal MARV infection when treatment is initiated up to 96 h PI.",2016 Feb 22,"['Warren, Travis K.', 'Whitehouse, Chris A.', 'Wells, Jay', 'Welch, Lisa', 'Charleston, Jay S.', 'Heald, Alison', 'Nichols, Donald K.', 'Mattix, Marc E.', 'Palacios, Gustavo', 'Kugleman, Jeffrey R.', 'Iversen, Patrick L.', 'Bavari, Sina']",PLoS Negl Trop Dis,,,True
9915073ee985307fd682c4df24810387ae83c338,PMC,RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines,http://dx.doi.org/10.1186/s12885-016-2197-1,PMC4765116,26911141,CC BY,"BACKGROUND: Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced “RNA disruption” is, the extent to which it is associated with drug response or what the underlying mechanisms are. METHODS: Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. RESULTS: All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3’-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. CONCLUSIONS: Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues and is associated with drug response. Although present, the link between apoptosis and RNA disruption is not completely understood. Evaluation of RNA disruption is thus proposed as a novel and effective biomarker to assess response to chemotherapy drugs in vitro and in vivo. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2197-1) contains supplementary material, which is available to authorized users.",2016 Feb 24,"['Narendrula, Rashmi', 'Mispel-Beyer, Kyle', 'Guo, Baoqing', 'Parissenti, Amadeo M.', 'Pritzker, Laura B.', 'Pritzker, Ken', 'Masilamani, Twinkle', 'Wang, Xiaohui', 'Lannér, Carita']",BMC Cancer,,,True
0df2a9766ade17a0d9a625ef02722fc167ee0526,PMC,Truncation of C-terminal 20 amino acids in PA-X contributes to adaptation of swine influenza virus in pigs,http://dx.doi.org/10.1038/srep21845,PMC4766433,26912401,CC BY,"The PA-X protein is a fusion protein incorporating the N-terminal 191 amino acids of the PA protein with a short C-terminal sequence encoded by an overlapping ORF (X-ORF) in segment 3 that is accessed by + 1 ribosomal frameshifting, and this X-ORF exists in either full length or a truncated form (either 61-or 41-condons). Genetic evolution analysis indicates that all swine influenza viruses (SIVs) possessed full-length PA-X prior to 1985, but since then SIVs with truncated PA-X have gradually increased and become dominant, implying that truncation of this protein may contribute to the adaptation of influenza virus in pigs. To verify this hypothesis, we constructed PA-X extended viruses in the background of a “triple-reassortment” H1N2 SIV with truncated PA-X, and evaluated their biological characteristics in vitro and in vivo. Compared with full-length PA-X, SIV with truncated PA-X had increased viral replication in porcine cells and swine respiratory tissues, along with enhanced pathogenicity, replication and transmissibility in pigs. Furthermore, we found that truncation of PA-X improved the inhibition of IFN-I mRNA expression. Hereby, our results imply that truncation of PA-X may contribute to the adaptation of SIV in pigs.",2016 Feb 25,"['Xu, Guanlong', 'Zhang, Xuxiao', 'Sun, Yipeng', 'Liu, Qinfang', 'Sun, Honglei', 'Xiong, Xin', 'Jiang, Ming', 'He, Qiming', 'Wang, Yu', 'Pu, Juan', 'Guo, Xin', 'Yang, Hanchun', 'Liu, Jinhua']",Sci Rep,,,True
61c8af64ef0a95e3f6dfc71ced3f94c2768e23d2,PMC,A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses,http://dx.doi.org/10.1038/srep22008,PMC4766503,26911565,CC BY,"A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. In light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, P9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses in vitro and in vivo, including influenza A virus H1N1, H3N2, H5N1, H7N7, H7N9, SARS-CoV and MERS-CoV. The antiviral activity of P9 was attributed to its high-affinity binding to viral glycoproteins, as well as the abundance of basic amino acids in its composition. After binding viral particles through viral surface glycoproteins, P9 entered into cells together with the viruses via endocytosis and prevented endosomal acidification, which blocked membrane fusion and subsequent viral RNA release. This study has paved the avenue for developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities.",2016 Feb 25,"['Zhao, Hanjun', 'Zhou, Jie', 'Zhang, Ke', 'Chu, Hin', 'Liu, Dabin', 'Poon, Vincent Kwok-Man', 'Chan, Chris Chung-Sing', 'Leung, Ho-Chuen', 'Fai, Ng', 'Lin, Yong-Ping', 'Zhang, Anna Jin-Xia', 'Jin, Dong-Yan', 'Yuen, Kwok-Yung', 'Zheng, Bo-Jian']",Sci Rep,,,True
94827ed2231500b8b66fde9844d2aebe81a4aba9,PMC,Niclosamide induced cell apoptosis via upregulation of ATF3 and activation of PERK in Hepatocellular carcinoma cells,http://dx.doi.org/10.1186/s12876-016-0442-3,PMC4766699,26917416,CC BY,"BACKGROUND: Hepatocellular carcinoma (HCC) is one of most common and aggressive human malignancies in the world, especially, in eastern Asia, and its mortality is very high at any phase. We want to investigate mechanism of niclosamide inducing cell apoptosis in HCC. METHODS: Two hepatoma cell lines were used to evaluate activity of niclosamide inducing cell apoptosis and study its mechanism. Quantitative real-time PCR and western blotting were used in analysis of genes expression or protein active regulated by niclosamide. RESULTS: Niclosamide remarkably induced cell apoptosis in hepatoma cells. Furthermore, our study revealed that RNA-dependent protein kinase-like kinase (PERK) is activated and its expression is up-regulated in HCC cells which are exposed to niclosamide. niclosamide also significantly increase activating transcription factor 3 (ATF3), activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein-homologous protein (CHOP) expression in HCC cells. It’s suggested that the function of niclosamide was abrogated by PERK inhibitor or absent ATF3. Expression of PERK and CHOP is correlated with ATF3 level in the cells. CONCLUSION: Taken together, our results indicate that ATF3 plays an integral role in ER stress activated and cell apoptosis induced by niclosamide in HCC cells. In this study, the new mechanism of niclosamide as anti-cancer we investigated, too.",2016 Feb 25,"['Weng, Shunyan', 'Zhou, Liang', 'Deng, Qing', 'Wang, Jiaxian', 'Yu, Yan', 'Zhu, Jianwei', 'Yuan, Yunsheng']",BMC Gastroenterol,,,True
1352ae42e48ab6a01c1282db023286ab4e39cbe9,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
c850c2c541b74c1028f99bcf751aae9b1e4a8fc0,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
c3f62bba43fe602e78239d8e8bf60e6c0e1fc008,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
99304ba131e8983452dca5ae9118747496d678a9,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
60ef899f357bb02c4a27dae76a76b3d01f057798,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
19c3185194bafe8e4d966d300b95478a29d32860,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
4f1ad2c0d597b19ba0cf7ce1a8114641876afc84,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
82e2f47ebd6563b442e05f5d247eb187abc87579,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
6e673126a8a28d78c1030b36603d190c1dd47286,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
a918e4f69a765616d8708c2267fb54ddb8644409,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,True
3846cb057daf0b69fec4d889ff8657d252d94509,PMC,Moving interdisciplinary science forward: integrating participatory modelling with mathematical modelling of zoonotic disease in Africa,http://dx.doi.org/10.1186/s40249-016-0110-4,PMC4766706,26916067,CC BY,"This review outlines the benefits of using multiple approaches to improve model design and facilitate multidisciplinary research into infectious diseases, as well as showing and proposing practical examples of effective integration. It looks particularly at the benefits of using participatory research in conjunction with traditional modelling methods to potentially improve disease research, control and management. Integrated approaches can lead to more realistic mathematical models which in turn can assist with making policy decisions that reduce disease and benefit local people. The emergence, risk, spread and control of diseases are affected by many complex bio-physical, environmental and socio-economic factors. These include climate and environmental change, land-use variation, changes in population and people’s behaviour. The evidence base for this scoping review comes from the work of a consortium, with the aim of integrating modelling approaches traditionally used in epidemiological, ecological and development research. A total of five examples of the impacts of participatory research on the choice of model structure are presented. Example 1 focused on using participatory research as a tool to structure a model. Example 2 looks at identifying the most relevant parameters of the system. Example 3 concentrates on identifying the most relevant regime of the system (e.g., temporal stability or otherwise), Example 4 examines the feedbacks from mathematical models to guide participatory research and Example 5 goes beyond the so-far described two-way interplay between participatory and mathematical approaches to look at the integration of multiple methods and frameworks. This scoping review describes examples of best practice in the use of participatory methods, illustrating their potential to overcome disciplinary hurdles and promote multidisciplinary collaboration, with the aim of making models and their predictions more useful for decision-making and policy formulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0110-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Grant, Catherine', 'Lo Iacono, Giovanni', 'Dzingirai, Vupenyu', 'Bett, Bernard', 'Winnebah, Thomas R. A.', 'Atkinson, Peter M.']",Infect Dis Poverty,,,False
9cda7cc79c0dee43d486d8165181e5b5ca09a817,PMC,Moving interdisciplinary science forward: integrating participatory modelling with mathematical modelling of zoonotic disease in Africa,http://dx.doi.org/10.1186/s40249-016-0110-4,PMC4766706,26916067,CC BY,"This review outlines the benefits of using multiple approaches to improve model design and facilitate multidisciplinary research into infectious diseases, as well as showing and proposing practical examples of effective integration. It looks particularly at the benefits of using participatory research in conjunction with traditional modelling methods to potentially improve disease research, control and management. Integrated approaches can lead to more realistic mathematical models which in turn can assist with making policy decisions that reduce disease and benefit local people. The emergence, risk, spread and control of diseases are affected by many complex bio-physical, environmental and socio-economic factors. These include climate and environmental change, land-use variation, changes in population and people’s behaviour. The evidence base for this scoping review comes from the work of a consortium, with the aim of integrating modelling approaches traditionally used in epidemiological, ecological and development research. A total of five examples of the impacts of participatory research on the choice of model structure are presented. Example 1 focused on using participatory research as a tool to structure a model. Example 2 looks at identifying the most relevant parameters of the system. Example 3 concentrates on identifying the most relevant regime of the system (e.g., temporal stability or otherwise), Example 4 examines the feedbacks from mathematical models to guide participatory research and Example 5 goes beyond the so-far described two-way interplay between participatory and mathematical approaches to look at the integration of multiple methods and frameworks. This scoping review describes examples of best practice in the use of participatory methods, illustrating their potential to overcome disciplinary hurdles and promote multidisciplinary collaboration, with the aim of making models and their predictions more useful for decision-making and policy formulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0110-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Grant, Catherine', 'Lo Iacono, Giovanni', 'Dzingirai, Vupenyu', 'Bett, Bernard', 'Winnebah, Thomas R. A.', 'Atkinson, Peter M.']",Infect Dis Poverty,,,True
f44786ccd9fbd63530866db7c60cac06fb9b0fb9,PMC,Using mutagenesis to explore conserved residues in the RNA-binding groove of influenza A virus nucleoprotein for antiviral drug development,http://dx.doi.org/10.1038/srep21662,PMC4768256,26916998,CC BY,"Nucleoprotein (NP) is the most abundant type of RNA-binding viral protein in influenza A virus–infected cells and is necessary for viral RNA transcription and replication. Recent studies demonstrated that influenza NP is a valid target for antiviral drug development. The surface of the groove, covered with numerous conserved residues between the head and body domains of influenza A NP, plays a crucial role in RNA binding. To explore the mechanism by which NP binds RNA, we performed a series of site-directed mutagenesis in the RNA-binding groove, followed by surface plasmon resonance (SPR), to characterize the interactions between RNA and NP. Furthermore, a role of Y148 in NP stability and NP-RNA binding was evaluated. The aromatic residue of Y148 was found to stack with a nucleotide base. By interrupting the stacking interaction between Y148 and an RNA base, we identified an influenza virus NP inhibitor, (E, E)-1,7-bis(4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5-dione; this inhibitor reduced the NP’s RNA-binding affinity and hindered viral replication. Our findings will be useful for the development of new drugs that disrupt the interaction between RNA and viral NP in the influenza virus.",2016 Feb 26,"['Liu, Chia-Lin', 'Hung, Hui-Chen', 'Lo, Shou-Chen', 'Chiang, Ching-Hui', 'Chen, I-Jung', 'Hsu, John T.-A.', 'Hou, Ming-Hon']",Sci Rep,,,True
a5bedf3a8d33e6b501c2203982eaaa5567011d86,PMC,Classical Swine Fever Virus vs. Classical Swine Fever Virus: The Superinfection Exclusion Phenomenon in Experimentally Infected Wild Boar,http://dx.doi.org/10.1371/journal.pone.0149469,PMC4768946,26919741,CC BY,"Two groups with three wild boars each were used: Group A (animals 1 to 3) served as the control, and Group B (animals 4 to 6) was postnatally persistently infected with the Cat01 strain of CSFV (primary virus). The animals, six weeks old and clinically healthy, were inoculated with the virulent strain Margarita (secondary virus). For exclusive detection of the Margarita strain, a specific qRT-PCR assay was designed, which proved not to have cross-reactivity with the Cat01 strain. The wild boars persistently infected with CSFV were protected from superinfection by the virulent CSFV Margarita strain, as evidenced by the absence of clinical signs and the absence of Margarita RNA detection in serum, swabs and tissue samples. Additionally, in PBMCs, a well-known target for CSFV viral replication, only the primary infecting virus RNA (Cat01 strain) could be detected, even after the isolation in ST cells, demonstrating SIE at the tissue level in vivo. Furthermore, the data analysis of the Margarita qRT-PCR, by means of calculated ΔCt values, supported that PBMCs from persistently infected animals were substantially protected from superinfection after in vitro inoculation with the Margarita virus strain, while this virus was able to infect naive PBMCs efficiently. In parallel, IFN-α values were undetectable in the sera from animals in Group B after inoculation with the CSFV Margarita strain. Furthermore, these animals were unable to elicit adaptive humoral (no E2-specific or neutralising antibodies) or cellular immune responses (in terms of IFN-γ-producing cells) after inoculation with the second virus. Finally, a sequence analysis could not detect CSFV Margarita RNA in the samples tested from Group B. Our results suggested that the SIE phenomenon might be involved in the evolution and phylogeny of the virus, as well as in CSFV control by vaccination. To the best of our knowledge, this study was one of the first showing efficient suppression of superinfection in animals, especially in the absence of IFN-α, which might be associated with the lack of innate immune mechanisms.",2016 Feb 26,"['Muñoz-González, Sara', 'Pérez-Simó, Marta', 'Colom-Cadena, Andreu', 'Cabezón, Oscar', 'Bohórquez, José Alejandro', 'Rosell, Rosa', 'Pérez, Lester Josué', 'Marco, Ignasi', 'Lavín, Santiago', 'Domingo, Mariano', 'Ganges, Llilianne']",PLoS One,,,True
31fa7844fdceee15b185eb734a7e1a09527431e2,PMC,High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling,http://dx.doi.org/10.1371/journal.ppat.1005473,PMC4769073,26919232,CC BY,"Members of the family Coronaviridae have the largest genomes of all RNA viruses, typically in the region of 30 kilobases. Several coronaviruses, such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV), are of medical importance, with high mortality rates and, in the case of SARS-CoV, significant pandemic potential. Other coronaviruses, such as Porcine epidemic diarrhea virus and Avian coronavirus, are important livestock pathogens. Ribosome profiling is a technique which exploits the capacity of the translating ribosome to protect around 30 nucleotides of mRNA from ribonuclease digestion. Ribosome-protected mRNA fragments are purified, subjected to deep sequencing and mapped back to the transcriptome to give a global “snap-shot” of translation. Parallel RNA sequencing allows normalization by transcript abundance. Here we apply ribosome profiling to cells infected with Murine coronavirus, mouse hepatitis virus, strain A59 (MHV-A59), a model coronavirus in the same genus as SARS-CoV and MERS-CoV. The data obtained allowed us to study the kinetics of virus transcription and translation with exquisite precision. We studied the timecourse of positive and negative-sense genomic and subgenomic viral RNA production and the relative translation efficiencies of the different virus ORFs. Virus mRNAs were not found to be translated more efficiently than host mRNAs; rather, virus translation dominates host translation at later time points due to high levels of virus transcripts. Triplet phasing of the profiling data allowed precise determination of translated reading frames and revealed several translated short open reading frames upstream of, or embedded within, known virus protein-coding regions. Ribosome pause sites were identified in the virus replicase polyprotein pp1a ORF and investigated experimentally. Contrary to expectations, ribosomes were not found to pause at the ribosomal frameshift site. To our knowledge this is the first application of ribosome profiling to an RNA virus.",2016 Feb 26,"['Irigoyen, Nerea', 'Firth, Andrew E.', 'Jones, Joshua D.', 'Chung, Betty Y.-W.', 'Siddell, Stuart G.', 'Brierley, Ian']",PLoS Pathog,,,True
b38901ead62c88fd24f7d28ca738711e13fb79ad,PMC,Mathematical modeling of the West Africa Ebola epidemic,http://dx.doi.org/10.7554/eLife.09186,PMC4769159,26646185,CC BY,"As of November 2015, the Ebola virus disease (EVD) epidemic that began in West Africa in late 2013 is waning. The human toll includes more than 28,000 EVD cases and 11,000 deaths in Guinea, Liberia, and Sierra Leone, the most heavily-affected countries. We reviewed 66 mathematical modeling studies of the EVD epidemic published in the peer-reviewed literature to assess the key uncertainties models addressed, data used for modeling, public sharing of data and results, and model performance. Based on the review, we suggest steps to improve the use of modeling in future public health emergencies. DOI: http://dx.doi.org/10.7554/eLife.09186.001",,"['Chretien, Jean-Paul', 'Riley, Steven', 'George, Dylan B']",eLife.; 4:e09186,,,True
af2e81683f4a37a0ada4acd6fbc495550306c86f,PMC,"Association between social support and recovery from post-traumatic stress disorder after flood: a 13–14 year follow-up study in Hunan, China",http://dx.doi.org/10.1186/s12889-016-2871-x,PMC4770534,26924178,CC BY,"BACKGROUND: Post-traumatic stress disorder (PTSD) is one of the most prevalent long-term psychiatric disorders among survivors of traumatic events. It is well established that social support has been related to the onset of PTSD after natural disasters. However, very little is known whether or not social support has had an influence on the recovery from the PTSD that was diagnosed after floods. This study, therefore, made a follow-up assessment of PTSD in flood victims 13–14 years after they were diagnosed with PTSD in 2000 to measure the prevalence rate of PTSD among them and identify the association between social support and their recovery from PTSD. METHODS: Victims who had experienced Dongting Lake flood in 1998 and had been diagnosed as having PTSD in 2000 were enrolled in this study. A follow-up survey was done between the years 2013 and 2014 to diagnose the victims again of PTSD using the DSM-IV criteria. Social support and its three dimensions were measured using the Chinese version of Social Support Rating Scale (SSRS), including objective support, subjective support and support utilization. Data were collected through face-to-face interviews using a structured questionnaire. Bivariate and multivariate logistic regression analyses were used to examine the relationship between social support and the recovery from PTSD after flood. RESULTS: Out of 321 subjects with prior PTSD, 51 (15.89 %) were diagnosed as still having PTSD. Logistic regression analyses indicated that the recovery from prior PTSD was significantly associated with social support (odds ratio (OR) =0.202, 95 % confidence interval (95 % CI): 0.047–0.878), subjective support (OR = 0.236, 95 % CI: 0.080–0.694) and support utilization (OR = 0.245, 95 % CI: 0.071–0.844). CONCLUSIONS: The prevalence rate of current PTSD indicates that natural disasters, such as floods, may affect the mental health of victims for a long time. Social support was significantly associated with the recovery from prior PTSD, especially subjective support and support utilization.",2016 Feb 29,"['Dai, Wenjie', 'Chen, Long', 'Tan, Hongzhuan', 'Wang, Jieru', 'Lai, Zhiwei', 'Kaminga, Atipatsa C.', 'Li, Yan', 'Liu, Aizhong']",BMC Public Health,,,True
dd48e5c738239c1d9b0497cbf4b5219bf252c0b8,PMC,Modelling input-output flows of severe acute respiratory syndrome in mainland China,http://dx.doi.org/10.1186/s12889-016-2867-6,PMC4770707,26924026,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS) originated in China in 2002, and it spread to 26 provinces in mainland China and 32 countries across five continents in a matter of months. This outbreak resulted in 774 deaths. However, the spatial features and potential determinants of SARS input-output flows remain unclear. METHODS: We used an adjusted spatial interaction model to examine the spatial effects and potential factors associated with SARS input-output flows. RESULTS: The presence of origin-based spatial dependence positively affected SARS input-output flows from the neighbours of the origin regions. Two components of the input-output flows, migrant and hospitalization flows, exhibited distinctive features. The origin-based and destination-based spatial dependence positively affected migrant flows (i.e., due to those seeking jobs) from the neighbours of origin and destination locations. Similarly, the destination-based spatial dependence also positively affected hospitalization flows (i.e., due to those seeking treatment) from the neighbours of destination regions. However, the origin-to-destination based spatial dependence negatively affected hospitalisation flows from the neighbours of origin-to-destination regions. The direct effects accounted for 78 % of the SARS input-output flows, which was 3.56-fold greater than the indirect effects. Differences in regional income drove the SARS input-output flows. Therefore, urban income had a positive effect, whereas rural income had a negative effect. Total interregional flows increased by 3.54 % with a 1 % increase in urban income, and intraregional flows increased by 8.35 %. In contrast, the total interregional flows decreased by 3.38 % with a 1 % increase in rural income, and intraregional flows declined by 2.29 %. Railway capacity, per person gross domestic product (PGDP), urban rate and the law of distance decay also affected the input-output flows. CONCLUSIONS: Our results confirm that the SARS input-output flows presented significant geographic spatial heterogeneity and spatial effects. Income differences were the major cause of the flows between pairs of regions. Railway capacity, PGDP, and urban rate also played important roles. These findings provide valuable information for the Chinese government to control the future spread of nationwide epidemics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-016-2867-6) contains supplementary material, which is available to authorized users.",2016 Feb 29,"['Wang, Li', 'Wang, Jinfeng', 'Xu, Chengdong', 'Liu, Tiejun']",BMC Public Health,,,True
d0146d4c8a05561b617e944b7f7c523c46612dc8,PMC,Myricetin: A Dietary Molecule with Diverse Biological Activities,http://dx.doi.org/10.3390/nu8020090,PMC4772053,26891321,CC BY,"Myricetin is a common plant-derived flavonoid and is well recognised for its nutraceuticals value. It is one of the key ingredients of various foods and beverages. The compound exhibits a wide range of activities that include strong anti-oxidant, anticancer, antidiabetic and anti-inflammatory activities. It displays several activities that are related to the central nervous system and numerous studies have suggested that the compound may be beneficial to protect against diseases such as Parkinson’s and Alzheimer’s. The use of myricetin as a preserving agent to extend the shelf life of foods containing oils and fats is attributed to the compound’s ability to protect lipids against oxidation. A detailed search of existing literature revealed that there is currently no comprehensive review available on this important molecule. Hence, the present work includes the history, synthesis, pharmaceutical applications and toxicity studies of myricetin. This report also highlights structure-activity relationships and mechanisms of action for various biological activities.",2016 Feb 16,"['Semwal, Deepak Kumar', 'Semwal, Ruchi Badoni', 'Combrinck, Sandra', 'Viljoen, Alvaro']",Nutrients,,,True
343aeda9b3a81a9db2f40386f3991ef6c48338ce,PMC,How Inhomogeneous Site Percolation Works on Bethe Lattices: Theory and Application,http://dx.doi.org/10.1038/srep22420,PMC4772486,26926785,CC BY,"Inhomogeneous percolation, for its closer relationship with real-life, can be more useful and reasonable than homogeneous percolation to illustrate the critical phenomena and dynamical behaviour of complex networks. However, due to its intricacy, the theoretical framework of inhomogeneous percolation is far from being complete and many challenging problems are still open. In this paper, we first investigate inhomogeneous site percolation on Bethe Lattices with two occupation probabilities, and then extend the result to percolation with m occupation probabilities. The critical behaviour of this inhomogeneous percolation is shown clearly by formulating the percolation probability [Image: see text] with given occupation probability p, the critical occupation probability [Image: see text], and the average cluster size [Image: see text] where p is subject to [Image: see text]. Moreover, using the above theory, we discuss in detail the diffusion behaviour of an infectious disease (SARS) and present specific disease-control strategies in consideration of groups with different infection probabilities.",2016 Mar 1,"['Ren, Jingli', 'Zhang, Liying', 'Siegmund, Stefan']",Sci Rep,,,True
a7655a74468e485dfd7f45390c5be4c4aa9361a8,PMC,Comparative Epidemiology of Human Infections with Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome Coronaviruses among Healthcare Personnel,http://dx.doi.org/10.1371/journal.pone.0149988,PMC4773072,26930074,CC BY,"The largest nosocomial outbreak of Middle East respiratory syndrome (MERS) occurred in South Korea in 2015. Health Care Personnel (HCP) are at high risk of acquiring MERS-Coronavirus (MERS-CoV) infections, similar to the severe acute respiratory syndrome (SARS)-Coronavirus (SARS-CoV) infections first identified in 2003. This study described the similarities and differences in epidemiological and clinical characteristics of 183 confirmed global MERS cases and 98 SARS cases in Taiwan associated with HCP. The epidemiological findings showed that the mean age of MERS-HCP and total MERS cases were 40 (24~74) and 49 (2~90) years, respectively, much older than those in SARS [SARS-HCP: 35 (21~68) years, p = 0.006; total SARS: 42 (0~94) years, p = 0.0002]. The case fatality rates (CFR) was much lower in MERS-HCP [7.03% (9/128)] or SARS-HCP [12.24% (12/98)] than the MERS-non-HCP [36.96% (34/92), p<0.001] or SARS-non-HCP [24.50% (61/249), p<0.001], however, no difference was found between MERS-HCP and SARS-HCP [p = 0.181]. In terms of clinical period, the days from onset to death [13 (4~17) vs 14.5 (0~52), p = 0.045] and to discharge [11 (5~24) vs 24 (0~74), p = 0.010] and be hospitalized days [9.5 (3~22) vs 22 (0~69), p = 0.040] were much shorter in MERS-HCP than SARS-HCP. Similarly, days from onset to confirmation were shorter in MERS-HCP than MERS-non-HCP [6 (1~14) vs 10 (1~21), p = 0.044]. In conclusion, the severity of MERS-HCP and SARS-HCP was lower than that of MERS-non-HCP and SARS-non-HCP due to younger age and early confirmation in HCP groups. However, no statistical difference was found in MERS-HCP and SARS-HCP. Thus, prevention of nosocomial infections involving both novel Coronavirus is crucially important to protect HCP.",2016 Mar 1,"['Liu, Shelan', 'Chan, Ta-Chien', 'Chu, Yu-Tseng', 'Wu, Joseph Tsung-Shu', 'Geng, Xingyi', 'Zhao, Na', 'Cheng, Wei', 'Chen, Enfu', 'King, Chwan-Chuen']",PLoS One,,,True
6620e8406c8ad908234205ff102d7bd2cc0dce72,PMC,Characterization and Vaccine Potential of Outer Membrane Vesicles Produced by Haemophilus parasuis,http://dx.doi.org/10.1371/journal.pone.0149132,PMC4773134,26930282,CC0,"Haemophilus parasuis is a Gram-negative bacterium that colonizes the upper respiratory tract of swine and is capable of causing a systemic infection, resulting in high morbidity and mortality. H. parasuis isolates display a wide range of virulence and virulence factors are largely unknown. Commercial bacterins are often used to vaccinate swine against H. parasuis, though strain variability and lack of cross-reactivity can make this an ineffective means of protection. Outer membrane vesicles (OMV) are spherical structures naturally released from the membrane of bacteria and OMV are often enriched in toxins, signaling molecules and other bacterial components. Examination of OMV structures has led to identification of virulence factors in a number of bacteria and they have been successfully used as subunit vaccines. We have isolated OMV from both virulent and avirulent strains of H. parasuis, have examined their protein content and assessed their ability to induce an immune response in the host. Vaccination with purified OMV derived from the virulent H. parasuis Nagasaki strain provided protection against challenge with a lethal dose of the bacteria.",2016 Mar 1,"['McCaig, William D.', 'Loving, Crystal L.', 'Hughes, Holly R.', 'Brockmeier, Susan L.']",PLoS One,,,True
ef39c95cda9c94452dc64147ea7d9c825e03b8bb,PMC,"Perception, Price and Preference: Consumption and Protection of Wild Animals Used in Traditional Medicine",http://dx.doi.org/10.1371/journal.pone.0145901,PMC4773180,26930487,CC BY,"A wide array of wildlife species, including many animals, are used in traditional medicines across many medicinal systems, including in Traditional Chinese Medicine (TCM). Due to over-exploitation and habitat loss, the populations of many animals commonly used in TCM have declined and are unable to meet market demand. A number of measures have been taken to try to reduce the impact that this large and growing market for TCM may have on wild animal species. Consumer preferences and behavior are known to play an important role in the consumption and protection of wild animals used in traditional medicine, and thus are likely to be an important factor in the success of many of these mechanisms—particularly given the significant percentage of TCMs that are over-the-counter products (access to which is not mediated by practitioners). In this study we conducted questionnaires and designed stated preference experiments embodying different simulation scenarios using a random sample of the population in Beijing to elicit individuals’ knowledge, perceptions and preferences toward wild or farmed animal materials and their substitutes used in traditional Chinese medicine. We found that respondents had a stated preference for wild materials over farm-raised and other alternatives because they believe that the effectiveness of wild-sourced materials is more credible than that of other sources. However, we also found that, although respondents used TCM products, they had a poor understanding of the function or composition of either traditional Chinese medicines or proprietary Chinese medicines (PCM), and paid little attention to the composition of products when making purchasing decisions. Furthermore, awareness of the need for species protection, or “conservation consciousness” was found to play an important role in willingness to accept substitutions for wild animal materials, while traditional animal medicinal materials (TAMs) derived from well-known endangered species, such as bear bile and tiger bone, show relatively higher substitutability. These results suggest that there is still hope for conservation measures which seek to promote a transition to farmed animal, plant and synthetic ingredients and provide clear directions for future social marketing, education and engagement efforts.",2016 Mar 1,"['Liu, Zhao', 'Jiang, Zhigang', 'Fang, Hongxia', 'Li, Chunwang', 'Mi, Aizi', 'Chen, Jing', 'Zhang, Xiaowei', 'Cui, Shaopeng', 'Chen, Daiqiang', 'Ping, Xiaoge', 'Li, Feng', 'Li, Chunlin', 'Tang, Songhua', 'Luo, Zhenhua', 'Zeng, Yan', 'Meng, Zhibin']",PLoS One,,,True
5ef330551dd1c93b532c49305501f9a5abd3d799,PMC,T Cell Response in Patients with Implanted Biological and Mechanical Prosthetic Heart Valves,http://dx.doi.org/10.1155/2016/1937564,PMC4773556,26989331,CC BY,"The study was aimed at assessing T cell subsets of peripheral blood from recipients of long-term functioning (more than 60 months) biological and mechanical heart valve prostheses. The absolute and relative number of CD4 and CD8 T cell subsets was analyzed: naïve (N, CD45RA(+)CD62L(+)), central memory (CM, CD45RA(−)CD62L(+)), effector memory (EM, CD45RA(−)CD62L(−)), and terminally differentiated CD45RA-positive effector memory (TEMRA, CD45RA(+)CD62L(−)) in 25 persons with biological and 7 with mechanical prosthesis compared with 48 apparently healthy volunteers. The relative and absolute number of central memory and naïve CD3(+)CD8(+) in patients with biological prosthesis was decreased (p < 0.001). Meanwhile the number of CD45RA(+)CD62L(−)CD3(+)CD8(+) and CD3(+)CD4(+) was increased (p < 0.001). Patients with mechanical prosthesis had increased absolute and relative number of CD45RA(+)CD62L(−)CD3(+)CD8(+) cells (p = 0.006). Also the relative number of CD3(+)CD4(+) cells was reduced (p = 0.04). We assume that altered composition of T cell subsets points at development of xenograft rejection reaction against both mechanical and biological heart valve prostheses.",2016 Feb 17,"['Barbarash, L.', 'Kudryavtsev, I.', 'Rutkovskaya, N.', 'Golovkin, A.']",Mediators Inflamm,,,True
681a28c40a3da8f03c0f86a91db26bc8416967ed,PMC,The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes,http://dx.doi.org/10.1186/s12864-016-2500-1,PMC4774177,26931144,CC BY,"BACKGROUND: The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci. RESULTS: Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is “Centromere - Class II – Class III – Class I”. DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist. CONCLUSIONS: This study provided evidence that camels possess an MHC comparable to other mammalian species in terms of its genomic localization, organization and sequence similarity. We described ancient variation at the DRA locus, monomorphic in most species. The extent of molecular diversity of MHC class II genes seems to be substantially lower in Old World camels than in other mammalian species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2500-1) contains supplementary material, which is available to authorized users.",2016 Mar 1,"['Plasil, Martin', 'Mohandesan, Elmira', 'Fitak, Robert R.', 'Musilova, Petra', 'Kubickova, Svatava', 'Burger, Pamela A.', 'Horin, Petr']",BMC Genomics,,,False
34829c7a24387bede0b75ec97fdd37e1a5ae6c4e,PMC,The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes,http://dx.doi.org/10.1186/s12864-016-2500-1,PMC4774177,26931144,CC BY,"BACKGROUND: The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci. RESULTS: Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is “Centromere - Class II – Class III – Class I”. DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist. CONCLUSIONS: This study provided evidence that camels possess an MHC comparable to other mammalian species in terms of its genomic localization, organization and sequence similarity. We described ancient variation at the DRA locus, monomorphic in most species. The extent of molecular diversity of MHC class II genes seems to be substantially lower in Old World camels than in other mammalian species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2500-1) contains supplementary material, which is available to authorized users.",2016 Mar 1,"['Plasil, Martin', 'Mohandesan, Elmira', 'Fitak, Robert R.', 'Musilova, Petra', 'Kubickova, Svatava', 'Burger, Pamela A.', 'Horin, Petr']",BMC Genomics,,,False
824044d0d0f1262cd632945cc54889335133a9bb,PMC,The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes,http://dx.doi.org/10.1186/s12864-016-2500-1,PMC4774177,26931144,CC BY,"BACKGROUND: The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci. RESULTS: Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is “Centromere - Class II – Class III – Class I”. DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist. CONCLUSIONS: This study provided evidence that camels possess an MHC comparable to other mammalian species in terms of its genomic localization, organization and sequence similarity. We described ancient variation at the DRA locus, monomorphic in most species. The extent of molecular diversity of MHC class II genes seems to be substantially lower in Old World camels than in other mammalian species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2500-1) contains supplementary material, which is available to authorized users.",2016 Mar 1,"['Plasil, Martin', 'Mohandesan, Elmira', 'Fitak, Robert R.', 'Musilova, Petra', 'Kubickova, Svatava', 'Burger, Pamela A.', 'Horin, Petr']",BMC Genomics,,,False
9cf367c15e9c4bbfea103bbb629fba2b48a20afc,PMC,The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes,http://dx.doi.org/10.1186/s12864-016-2500-1,PMC4774177,26931144,CC BY,"BACKGROUND: The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci. RESULTS: Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is “Centromere - Class II – Class III – Class I”. DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist. CONCLUSIONS: This study provided evidence that camels possess an MHC comparable to other mammalian species in terms of its genomic localization, organization and sequence similarity. We described ancient variation at the DRA locus, monomorphic in most species. The extent of molecular diversity of MHC class II genes seems to be substantially lower in Old World camels than in other mammalian species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2500-1) contains supplementary material, which is available to authorized users.",2016 Mar 1,"['Plasil, Martin', 'Mohandesan, Elmira', 'Fitak, Robert R.', 'Musilova, Petra', 'Kubickova, Svatava', 'Burger, Pamela A.', 'Horin, Petr']",BMC Genomics,,,False
cb7cb23bf68e88cbd3334bb46eb899d7a873d115,PMC,The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes,http://dx.doi.org/10.1186/s12864-016-2500-1,PMC4774177,26931144,CC BY,"BACKGROUND: The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci. RESULTS: Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is “Centromere - Class II – Class III – Class I”. DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist. CONCLUSIONS: This study provided evidence that camels possess an MHC comparable to other mammalian species in terms of its genomic localization, organization and sequence similarity. We described ancient variation at the DRA locus, monomorphic in most species. The extent of molecular diversity of MHC class II genes seems to be substantially lower in Old World camels than in other mammalian species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2500-1) contains supplementary material, which is available to authorized users.",2016 Mar 1,"['Plasil, Martin', 'Mohandesan, Elmira', 'Fitak, Robert R.', 'Musilova, Petra', 'Kubickova, Svatava', 'Burger, Pamela A.', 'Horin, Petr']",BMC Genomics,,,False
15dd9abbe4084c12712f094415c5ca9980aaacda,PMC,The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes,http://dx.doi.org/10.1186/s12864-016-2500-1,PMC4774177,26931144,CC BY,"BACKGROUND: The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci. RESULTS: Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is “Centromere - Class II – Class III – Class I”. DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist. CONCLUSIONS: This study provided evidence that camels possess an MHC comparable to other mammalian species in terms of its genomic localization, organization and sequence similarity. We described ancient variation at the DRA locus, monomorphic in most species. The extent of molecular diversity of MHC class II genes seems to be substantially lower in Old World camels than in other mammalian species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2500-1) contains supplementary material, which is available to authorized users.",2016 Mar 1,"['Plasil, Martin', 'Mohandesan, Elmira', 'Fitak, Robert R.', 'Musilova, Petra', 'Kubickova, Svatava', 'Burger, Pamela A.', 'Horin, Petr']",BMC Genomics,,,True
a127919cf960d1c72c3e29ce2ec08c67d6aba59f,PMC,"Construction and characterization of recombinant human adenovirus type 5 expressing foot-and-mouth disease virus capsid proteins of Indian vaccine strain, O/IND/R2/75",http://dx.doi.org/10.14202/vetworld.2015.147-155,PMC4774695,27047064,CC BY,"AIM: Generation of recombinant human adenovirus type 5 expressing foot-and-mouth disease virus (FMDV) capsid protein genes along with full-length 2B, 3B and 3C(pro) and its characterization. MATERIALS AND METHODS: FMD viral RNA isolation, cDNA synthesis, and polymerase chain reaction were performed to synthesize expression cassettes (P1-2AB3BC(wt) and P1-2AB3BC(m)) followed by cloning in pShuttle-CMV vector. Chemically competent BJ5183-AD-1 cells were transformed with the recombinant pShuttle-CMV to produce recombinant adenoviral plasmids. HEK-293 cells were transfected with the recombinant adenoviral plasmids to generate recombinant adenoviruses (hAd5/P1-2AB3BC(wt) and hAd5/P1-2AB3BC(m)). Expression of the target proteins was analyzed by sandwich ELISA and indirect immunofluorescence assay. The recombinant adenoviruses were purified and concentrated by CsCl density gradient ultracentrifugation. Growth kinetics and thermostability of the recombinant adenoviruses were compared with that of non-recombinant replication-defective adenovirus (dAd5). RESULTS: The recombinant adenoviruses containing capsid protein genes of the FMDV O/IND/R2/75 were generated and amplified in HEK-293 cells. The titer of the recombinant adenoviruses was approximately 10(8), 10(9.5) and 10(11) TCID(50)/ml in supernatant media, cell lysate and CsCl purified preparation, respectively. Expression of the FMDV capsid protein was detectable in sandwich ELISA and confirmed by immunofluorescence assay. Growth kinetics of the recombinant adenoviruses did not reveal a significant difference when compared with that of dAd5. A decrement of up to 10-fold at 4°C and 21-fold at 37°C was recorded in the virus titers during 60 h incubation period and found to be statistically significant (p<0.01). CONCLUSION: Recombinant adenoviruses expressing capsid proteins of the FMDV O/IND/R2/75 were constructed and produced in high titers. In vitro expression of the target proteins in the adenovirus vector system was detected by sandwich ELISA and immunofluorescence assay.",2015 Feb 10,"['Kumar, Ramesh', 'Sreenivasa, B. P.', 'Tamilselvan, R. P.']",Vet World,,,True
b6b06d62a3af9c36824d3c674f4d43d6d78d9073,PMC,Validation of γ-radiation and ultraviolet as a new inactivators for foot and mouth disease virus in comparison with the traditional methods,http://dx.doi.org/10.14202/vetworld.2015.1088-1098,PMC4774778,27047204,CC BY,"AIM: The present work deals with different methods for foot and mouth disease virus (FMDV) inactivation for serotypes O/pan Asia, A/Iran05, and SAT-2/2012 by heat, gamma radiation, and ultraviolet (UV) in comparison with the traditional methods and their effects on the antigenicity of viruses for production of inactivated vaccines. MATERIALS AND METHODS: FMDV types O/pan Asia, A/Iran05, and SAT-2/2012 were propagated in baby hamster kidney 21 (BHK21) and titrated then divided into five parts; the first part inactivated with heat, the second part inactivated with gamma radiation, the third part inactivated with UV light, the fourth part inactivated with binary ethylamine, and the last part inactivated with combination of binary ethylamine and formaldehyde (BEI+FA). Evaluate the method of inactivation via inoculation in BHK21, inoculation in suckling baby mice and complement fixation test then formulate vaccine using different methods of inactivation then applying the quality control tests to evaluate each formulated vaccine. RESULTS: The effect of heat, gamma radiation, and UV on the ability of replication of FMDV “O/pan Asia, A/Iran05, and SAT-2/2012” was determined through BHK cell line passage. Each of the 9 virus aliquots titer 10(8) TCID(50) (3 for each strain) were exposed to 37, 57, and 77°C for 15, 30, and 45 min. Similarly, another 15 aliquots (5 for each strain) contain 1 mm depth of the exposed samples in petri-dish was exposed to UV light (252.7 nm wavelength: One foot distance) for 15, 30, 45, 60, and 65 min. Different doses of gamma radiation (10, 20, 25, 30, 35, 40, 45, 50, 55, and 60 KGy) were applied in a dose rate 0.551 Gy/s for each strain and repeated 6 times for each dose. FMDV (O/pan Asia, A/Iran05, and SAT-2/2012) were inactivated when exposed to heat ≥57°C for 15 min. The UV inactivation of FMDV (O/pan Asia and SAT-2) was obtained within 60 min and 65 min for type A/Iran05. The ideal dose for inactivation of FMDV (O/pan Asia, A/Iran05, and SAT-2/2012) with gamma radiation were 55-60 and 45 kGy, respectively. Inactivation of FMDV with binary was 20, 24 and 16 hr for O/pan Asia, A/Iran05, and SAT-2/2012, respectively while inactivation by (BEI+FA) was determined after 18, 19 and 11 hr for O/pan-Asia, A/Iran 05, and SAT-2/2012, respectively. The antigenicity of control virus before inactivation was 1/32, it was not changed after inactivation in case of gamma radiation and (BEI+FA) and slightly decrease to 1/16 in case of binary and declined to 1/2, 1/4 in case of heat and UV inactivation, respectively. The immune response induced by inactivated FMD vaccines by gamma radiation and (BEI+FA) lasted to 9 months post-vaccination, while the binary only still up to 8 months post-vaccination but heat and UV-inactivated vaccines were not effective. CONCLUSION: Gamma radiation could be considered a good new inactivator inducing the same results of inactivated vaccine by binary with formaldehyde (BEI+FA).",2015 Sep 19,"['Mahdy, Safy El din', 'Hassanin, Amr Ismail', 'Gamal El-Din, Wael Mossad', 'Ibrahim, Ehab El-Sayed', 'Fakhry, Hiam Mohamed']",Vet World,,,True
9ce0da57763dfa3cebfb1463093ff0bba3333a25,PMC,"Prevalence of Cryptosporidia, Eimeria, Giardia, and Strongyloides in pre-weaned calves on smallholder dairy farms in Mukurwe-ini district, Kenya",http://dx.doi.org/10.14202/vetworld.2015.1118-1125,PMC4774781,27047207,CC BY,"AIM: Gastrointestinal diseases are among the leading causes of calf morbidity and mortality in Kenya and elsewhere. This study was undertaken to determine the prevalence of Cryptosporidia, Eimeria, Giardia, and Strongyloides in calves on smallholder dairy farms (SDF) in Mukurwe-ini District, Nyeri County, Kenya. These infections have been associated with economic losses by decreased growth rates, decreased productivity, and increased susceptibility to other diseases. MATERIALS AND METHODS: An observational study was conducted on 109 farms in Mukurwe-ini District, Nyeri County, Kenya, where 220 calf fecal samples (each calf at 4 and 6 weeks of age) from 110 calves (1 set of twins) were collected and analyzed for Cryptosporidia, Eimeria, Giardia, and helminth parasites. RESULTS: Eimeria oocysts, Cryptosporidia oocysts, and Strongyloides eggs were detected in the fecal samples examined, but no Giardia cysts were found. The overall period prevalence of Eimeria, Cryptosporidia, and Strongyloides was 42.7% (47/110), 13.6% (15/110), and 5.4% (6/110), respectively. The prevalence at 4 weeks of age for Eimeria, Cryptosporidia, and Strongyloides was 30.0% (33/110), 8.2% (9/110), and 3.7% (4/109), respectively, while the prevalence at 6 weeks of age was 20.2% (22/109), 6.5% (7/107), and 2.7% (3/110), respectively. There was, however, no significant difference in the prevalence at 4 and 6 weeks (p>0.05). CONCLUSION: Findings from this study show that Eimeria, Cryptosporidia, and Strongyloides, are prevalent in the study area and indicate the need to adopt optimal management practices to control infections in calves.",2015 Sep 22,"['Peter, Getrude Shepelo', 'Gitau, George Karuoya', 'Mulei, Charles Matiku', 'Vanleeuwen, John', 'Richards, Shauna', 'Wichtel, Jeff', 'Uehlinger, Fabienne', 'Mainga, Omwando']",Vet World,,,True
f880418303ca5f21c858eca97f076216919bb4b5,PMC,Defensins Potentiate a Neutralizing Antibody Response to Enteric Viral Infection,http://dx.doi.org/10.1371/journal.ppat.1005474,PMC4774934,26933888,CC BY,"α-defensins are abundant antimicrobial peptides with broad, potent antibacterial, antifungal, and antiviral activities in vitro. Although their contribution to host defense against bacteria in vivo has been demonstrated, comparable studies of their antiviral activity in vivo are lacking. Using a mouse model deficient in activated α-defensins in the small intestine, we show that Paneth cell α-defensins protect mice from oral infection by a pathogenic virus, mouse adenovirus 1 (MAdV-1). Survival differences between mouse genotypes are lost upon parenteral MAdV-1 infection, strongly implicating a role for intestinal defenses in attenuating pathogenesis. Although differences in α-defensin expression impact the composition of the ileal commensal bacterial population, depletion studies using broad-spectrum antibiotics revealed no effect of the microbiota on α-defensin-dependent viral pathogenesis. Moreover, despite the sensitivity of MAdV-1 infection to α-defensin neutralization in cell culture, we observed no barrier effect due to Paneth cell α-defensin activation on the kinetics and magnitude of MAdV-1 dissemination to the brain. Rather, a protective neutralizing antibody response was delayed in the absence of α-defensins. This effect was specific to oral viral infection, because antibody responses to parenteral or mucosal ovalbumin exposure were not affected by α-defensin deficiency. Thus, α-defensins play an important role as adjuvants in antiviral immunity in vivo that is distinct from their direct antiviral activity observed in cell culture.",2016 Mar 2,"['Gounder, Anshu P.', 'Myers, Nicolle D.', 'Treuting, Piper M.', 'Bromme, Beth A.', 'Wilson, Sarah S.', 'Wiens, Mayim E.', 'Lu, Wuyuan', 'Ouellette, André J.', 'Spindler, Katherine R.', 'Parks, William C.', 'Smith, Jason G.']",PLoS Pathog,,,True
d21eaa427bea34a60db8a4fec53ee3a5021a1eba,PMC,CpG Improves Influenza Vaccine Efficacy in Young Adult but Not Aged Mice,http://dx.doi.org/10.1371/journal.pone.0150425,PMC4774967,26934728,CC BY,"Several studies have shown a reduced efficacy of influenza vaccines in the elderly compared to young adults. In this study, we evaluated the immunogenicity and protective efficacy of a commercially available inactivated influenza vaccine (Fluzone(®)) in young adult and aged mice. C57/BL6 mice were administered a single or double immunization of Fluzone(®) with or without CpG and challenged intranasally with H1N1 A/California/09 virus. A double immunization of Fluzone(®) adjuvanted with CpG elicited the highest level of protection in young adult mice which was associated with increases in influenza specific IgG, elevated HAI titres, reduced viral titres and lung inflammation. In contrast, the vaccine schedule which provided fully protective immunity in young adult mice conferred limited protection in aged mice. Antigen presenting cells from aged mice were found to be less responsive to in vitro stimulation by Fluzone and CpG which may partially explain this result. Our data are supportive of studies that have shown limited effectiveness of influenza vaccines in the elderly and provide important information relevant to the design of more immunogenic vaccines in this age group.",2016 Mar 2,"['Ramirez, Alejandro', 'Co, Mary', 'Mathew, Anuja']",PLoS One,,,True
69060a231f9cae90c08c07b01d74da4f699cee8b,PMC,Modes of Antiviral Action of Chemical Portions and Constituents from Woad Root Extract against Influenza Virus A FM1,http://dx.doi.org/10.1155/2016/2537294,PMC4775799,26989425,CC BY,"Woad root has been used for the prevention of influenza for hundreds of years in many Asian countries. In this study, the antiviral modes of clemastanin B (CB), epigoitrin, phenylpropanoid portion (PEP), and the mixture of phenylpropanoids, alkaloids, and organic acid portions (PEP + ALK + OA) from wood root extract against influenza virus A FM1 were investigated. The results revealed that CB, epigoitrin, PEP, and PEP + ALK + OA exert their anti-influenza activity via inhibiting the virus multiplication, prophylaxis, and blocking the virus attachment. The primary mode of action of PEP and PEP + ALK + OA is the inhibition of virus replication. The inhibitory effect on virus attachment and multiplication is the main modes for epigoitrin. All the compounds or chemical portions from woad root extract tested in this study do not have direct virucidal activity. Our results provided the comprehensive analysis of the antiviral mechanism of wood root extract.",2016 Feb 18,"['Su, Jia-Hang', 'Diao, Rui-Gang', 'Lv, Shu-Guang', 'Mou, Xiao-Dong', 'Li, Kefeng']",Evid Based Complement Alternat Med,,,False
be738f9bf3b9a980ffecede2db4d06ea3f2518bd,PMC,Modes of Antiviral Action of Chemical Portions and Constituents from Woad Root Extract against Influenza Virus A FM1,http://dx.doi.org/10.1155/2016/2537294,PMC4775799,26989425,CC BY,"Woad root has been used for the prevention of influenza for hundreds of years in many Asian countries. In this study, the antiviral modes of clemastanin B (CB), epigoitrin, phenylpropanoid portion (PEP), and the mixture of phenylpropanoids, alkaloids, and organic acid portions (PEP + ALK + OA) from wood root extract against influenza virus A FM1 were investigated. The results revealed that CB, epigoitrin, PEP, and PEP + ALK + OA exert their anti-influenza activity via inhibiting the virus multiplication, prophylaxis, and blocking the virus attachment. The primary mode of action of PEP and PEP + ALK + OA is the inhibition of virus replication. The inhibitory effect on virus attachment and multiplication is the main modes for epigoitrin. All the compounds or chemical portions from woad root extract tested in this study do not have direct virucidal activity. Our results provided the comprehensive analysis of the antiviral mechanism of wood root extract.",2016 Feb 18,"['Su, Jia-Hang', 'Diao, Rui-Gang', 'Lv, Shu-Guang', 'Mou, Xiao-Dong', 'Li, Kefeng']",Evid Based Complement Alternat Med,,,True
64f5af205494b75764762ed86fd202387c77b0b7,PMC,"Spatial and Temporal Epidemiology of Lumpy Skin Disease in the Middle East, 2012–2015",http://dx.doi.org/10.3389/fvets.2016.00019,PMC4776163,26973845,CC BY,"Lumpy skin disease virus (LSDV) is an infectious disease of cattle that can have severe economic implications. New LSD outbreaks are currently circulating in the Middle East (ME). Since 2012, severe outbreaks were reported in cattle across the region. Characterizing the spatial and temporal dynamics of LSDV in cattle populations is prerequisite for guiding successful surveillance and control efforts at a regional level in the ME. Here, we aim to model the ecological niche of LSDV and identify epidemic progression patterns over the course of the epidemic. We analyzed publically available outbreak data from the ME for the period 2012–2015 using presence-only maximum entropy ecological niche modeling and the time-dependent method for the estimation of the effective reproductive number (R-TD). High-risk areas (probability >0.60) for LSDV identified by ecological niche modeling included parts of many northeastern ME countries, though Israel and Turkey were estimated to be the most suitable locations for occurrence of LSDV outbreaks. The most important environmental predictors that contributed to the ecological niche of LSDV included annual precipitation, land cover, mean diurnal range, type of livestock production system, and global livestock densities. Average monthly effective R-TD was equal to 2.2 (95% CI: 1.2, 3.5), whereas the largest R-TD was estimated in Israel (R-TD = 22.2, 95 CI: 15.2, 31.5) in September 2013, which indicated that the demographic and environmental conditions during this period were suitable to LSDV super-spreading events. The sharp drop of Isreal’s inferred R-TD in the following month reflected the success of their 2013 vaccination campaign in controlling the disease. Our results identified areas in which underreporting of LSDV outbreaks may have occurred. More epidemiological information related to cattle populations are needed to further improve the inferred spatial and temporal characteristics of currently circulating LSDV. However, the methodology presented here may be useful in guiding the design of risk-based surveillance and control programs in the region as well as aid in the formulation of epidemic preparedness plans in neighboring LSDV-free countries.",2016 Mar 3,"['Alkhamis, Mohammad A.', 'VanderWaal, Kimberly']",Front Vet Sci,,,True
1adab26eb1167a39014dc503174f7d34f9087664,PMC,Pandemic Influenza A (H1N1) Virus Infection Increases Apoptosis and HIV-1 Replication in HIV-1 Infected Jurkat Cells,http://dx.doi.org/10.3390/v8020033,PMC4776188,26848681,CC BY,"Influenza virus infection has a significant impact on public health, since it is a major cause of morbidity and mortality. It is not well-known whether influenza virus infection affects cell death and human immunodeficiency virus (HIV)-1 replication in HIV-1-infected patients. Using a lymphoma cell line, Jurkat, we examined the in vitro effects of pandemic influenza A (H1N1) virus (pH1N1) infection on cell death and HIV-1 RNA production in infected cells. We found that pH1N1 infection increased apoptotic cell death through Fas and Bax-mediated pathways in HIV-1-infected Jurkat cells. Infection with pH1N1 virus could promote HIV-1 RNA production by activating host transcription factors including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), nuclear factor of activated T-cells (NFAT) and activator protein 1 (AP-1) through mitogen-activated protein kinases (MAPK) pathways and T-cell antigen receptor (TCR)-related pathways. The replication of HIV-1 latent infection could be reactivated by pH1N1 infection through TCR and apoptotic pathways. These data indicate that HIV-1 replication can be activated by pH1N1 virus in HIV-1-infected cells resulting in induction of cell death through apoptotic pathways.",2016 Feb 2,"['Wang, Xue', 'Tan, Jiying', 'Biswas, Santanu', 'Zhao, Jiangqin', 'Devadas, Krishnakumar', 'Ye, Zhiping', 'Hewlett, Indira']",Viruses,,,True
0d6a45540d196e47056de4ba18b8b5b3429d3407,PMC,Pandemic Influenza A (H1N1) Virus Infection Increases Apoptosis and HIV-1 Replication in HIV-1 Infected Jurkat Cells,http://dx.doi.org/10.3390/v8020033,PMC4776188,26848681,CC BY,"Influenza virus infection has a significant impact on public health, since it is a major cause of morbidity and mortality. It is not well-known whether influenza virus infection affects cell death and human immunodeficiency virus (HIV)-1 replication in HIV-1-infected patients. Using a lymphoma cell line, Jurkat, we examined the in vitro effects of pandemic influenza A (H1N1) virus (pH1N1) infection on cell death and HIV-1 RNA production in infected cells. We found that pH1N1 infection increased apoptotic cell death through Fas and Bax-mediated pathways in HIV-1-infected Jurkat cells. Infection with pH1N1 virus could promote HIV-1 RNA production by activating host transcription factors including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), nuclear factor of activated T-cells (NFAT) and activator protein 1 (AP-1) through mitogen-activated protein kinases (MAPK) pathways and T-cell antigen receptor (TCR)-related pathways. The replication of HIV-1 latent infection could be reactivated by pH1N1 infection through TCR and apoptotic pathways. These data indicate that HIV-1 replication can be activated by pH1N1 virus in HIV-1-infected cells resulting in induction of cell death through apoptotic pathways.",2016 Feb 2,"['Wang, Xue', 'Tan, Jiying', 'Biswas, Santanu', 'Zhao, Jiangqin', 'Devadas, Krishnakumar', 'Ye, Zhiping', 'Hewlett, Indira']",Viruses,,,False
67e43e9157face441254689d2bab22b781f6b989,PMC,The Role of HBZ in HTLV-1-Induced Oncogenesis,http://dx.doi.org/10.3390/v8020034,PMC4776189,26848677,CC BY,"Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and chronic inflammatory diseases. HTLV-1 bZIP factor (HBZ) is transcribed as an antisense transcript of the HTLV-1 provirus. Among the HTLV-1-encoded viral genes, HBZ is the only gene that is constitutively expressed in all ATL cases. Recent studies have demonstrated that HBZ plays an essential role in oncogenesis by regulating viral transcription and modulating multiple host factors, as well as cellular signaling pathways, that contribute to the development and continued growth of cancer. In this article, I summarize the current knowledge of the oncogenic function of HBZ in cell proliferation, apoptosis, T-cell differentiation, immune escape, and HTLV-1 pathogenesis.",2016 Feb 2,"Zhao, Tiejun",Viruses,,,True
f7b30ee89775bc82607cc6bc87feb5934b47625f,PMC,"Viruses Causing Gastroenteritis: The Known, The New and Those Beyond",http://dx.doi.org/10.3390/v8020042,PMC4776197,26867198,CC BY,"The list of recently discovered gastrointestinal viruses is expanding rapidly. Whether these agents are actually involved in a disease such as diarrhea is the essential question, yet difficult to answer. In this review a summary of all viruses found in diarrhea is presented, together with the current knowledge about their connection to disease.",2016 Feb 19,"['Oude Munnink, Bas B.', 'van der Hoek, Lia']",Viruses,,,True
21da52646864c1ad3303daf10f0b3e4c9d12fa5c,PMC,Structural Proteomics of Herpesviruses,http://dx.doi.org/10.3390/v8020050,PMC4776205,26907323,CC BY,"Herpesviruses are highly prevalent viruses associated with numerous pathologies both in animal and human populations. Until now, most of the strategies used to prevent or to cure these infections have been unsuccessful because these viruses have developed numerous immune evasion mechanisms. Therefore, a better understanding of their complex lifecycle is needed. In particular, while the genome of numerous herpesviruses has been sequenced, the exact composition of virions remains unknown for most of them. Mass spectrometry has recently emerged as a central method and has permitted fundamental discoveries in virology. Here, we review mass spectrometry-based approaches that have recently allowed a better understanding of the composition of the herpesvirus virion. In particular, we describe strategies commonly used for proper sample preparation and fractionation to allow protein localization inside the particle but also to avoid contamination by nonstructural proteins. A collection of other important data regarding post-translational modifications or the relative abundance of structural proteins is also described. This review also discusses the poorly studied importance of host proteins in herpesvirus structural proteins and the necessity to develop a quantitative workflow to better understand the dynamics of the structural proteome. In the future, we hope that this collaborative effort will assist in the development of new strategies to fight these infections.",2016 Feb 12,"['Leroy, Baptiste', 'Gillet, Laurent', 'Vanderplasschen, Alain', 'Wattiez, Ruddy']",Viruses,,,True
9c8a4fff809abaa0b5ede6a28db62da5edd082e1,PMC,Identification of Known and Novel Recurrent Viral Sequences in Data from Multiple Patients and Multiple Cancers,http://dx.doi.org/10.3390/v8020053,PMC4776208,26907326,CC BY,"Virus discovery from high throughput sequencing data often follows a bottom-up approach where taxonomic annotation takes place prior to association to disease. Albeit effective in some cases, the approach fails to detect novel pathogens and remote variants not present in reference databases. We have developed a species independent pipeline that utilises sequence clustering for the identification of nucleotide sequences that co-occur across multiple sequencing data instances. We applied the workflow to 686 sequencing libraries from 252 cancer samples of different cancer and tissue types, 32 non-template controls, and 24 test samples. Recurrent sequences were statistically associated to biological, methodological or technical features with the aim to identify novel pathogens or plausible contaminants that may associate to a particular kit or method. We provide examples of identified inhabitants of the healthy tissue flora as well as experimental contaminants. Unmapped sequences that co-occur with high statistical significance potentially represent the unknown sequence space where novel pathogens can be identified.",2016 Feb 19,"['Friis-Nielsen, Jens', 'Kjartansdóttir, Kristín Rós', 'Mollerup, Sarah', 'Asplund, Maria', 'Mourier, Tobias', 'Jensen, Randi Holm', 'Hansen, Thomas Arn', 'Rey-Iglesia, Alba', 'Richter, Stine Raith', 'Nielsen, Ida Broman', 'Alquezar-Planas, David E.', 'Olsen, Pernille V. S.', 'Vinner, Lasse', 'Fridholm, Helena', 'Nielsen, Lars Peter', 'Willerslev, Eske', 'Sicheritz-Pontén, Thomas', 'Lund, Ole', 'Hansen, Anders Johannes', 'Izarzugaza, Jose M. G.', 'Brunak, Søren']",Viruses,,,True
d6a34d159840a3895ac1768920a1c498d3c448c6,PMC,Impact of Middle East Respiratory Syndrome coronavirus (MERS‐CoV) on pregnancy and perinatal outcome,http://dx.doi.org/10.1186/s12879-016-1437-y,PMC4776369,26936356,CC BY,"BACKGROUND: Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a viral respiratory disease. Most people infected with MERS-CoV develop severe acute respiratory illness. It was first reported in Saudi Arabia in 2012 and has since spread to several other countries. We report the clinical course of MERS-CoV infection in a pregnant woman who acquired the infection during the last trimester. CASE PRESENTATION: The patient is a 33-year-old female working as a critical care nurse. She was 32 weeks pregnant when she presented with respiratory symptoms after direct contact with a MERS-COV patient. Although the patient was in respiratory failure, necessitated mechanical ventilation, and intensive care (ICU) admission, a healthy infant was delivered. The mother recovered. To the best of our knowledge, this is the first reported case of a laboratory-confirmed Middle East Respiratory Syndrome Coronavirus in a pregnant woman. CONCLUSIONS: Middle East Respiratory Syndrome coronavirus (MERS-CoV) known to cause severe acute respiratory illness associated with a high risk of mortality Various factors may have contributed to the successful outcome of this patient such as young age, presentation during the last stages of pregnancy, and possible differences in immune response.",2016 Mar 2,"['Alserehi, Haleema', 'Wali, Ghassan', 'Alshukairi, Abeer', 'Alraddadi, Basem']",BMC Infect Dis,,,True
192e7d37cf521798de0394c2ad593f2bb77f5a77,PMC,"Obvious and Hidden Anxiety and the Related Factors in Operating Room Nurses Employed in General Hospital, Qazvin, Iran: A Cross-Sectional Study",http://dx.doi.org/10.5539/gjhs.v5n6p202,PMC4776884,24171889,CC BY,"BACKGROUND: Health promotion and security of manpower in a society is one of the pillars to progress a society. Anxiety, is the most common psychological disorder in societies and occupations like nursing, anesthesia technicians and operation room technicians. The aim of this study was to investigate prevalence of anxiety, and its severity in Iranian nurses working in operation room. Also, we determined the most important associated factors with anxiety. METHODS: In this cross sectional study, 152 nurses working in operating room participated. The tool to gather the data was a questionnaire, that included three parts; demographic information, obvious anxiety questions and hidden anxiety questions of Spielburger. Obtained data was analysed with SPSS 16 software. RESULTS: The majority of participants were females (94.7%) with experience at work less than 10 years (84.9%). The average scores of participants in obvious and hidden anxiety were 41.9±39.4 (range 20 to 75) and 39.4±8.2 (range 20 to 70), respectively. Anxiety level was significantly higher in females than males (P=0.04). The most prevalent cause of anxiety, was contact with infected biological factors (23% of nurses). The less important cause was concern about retirement (42.8% of nurses). CONCLUSION: Our results suggest that, anxiety disorders is prevalent in Iranian nurses working in public city hospitals, which warrants immediate programs for intervention to improve working situations in work place.",2013 Nov 29,"['Kayalha, Hamid', 'Yazdi, Zohreh', 'Rastak, Shahram', 'Dizaniha, Mojtaba']",Glob J Health Sci,,,True
1f7b47ec5e68a274a145bddd152303eba2f9d035,PMC,"Pandemic Influenza A (H1N1) and Its Prevention: A Cross Sectional Study on Patients’ Knowledge, Attitude and Practice among Patients Attending Primary Health Care Clinic in Kuala Lumpur, Malaysia",http://dx.doi.org/10.5539/gjhs.v4n2p95,PMC4777058,22980156,CC BY,"The World Health Organization confirmed that the novel influenza A, H1N1 as a pandemic on 11 June 2009. After less than three months, 182 countries were affected by the pandemic accounting for about 150,000 infected cases and 3000 mortality. Successful H1N1 pandemic management strategies’ shaped by making changes in health behavior. The aim of this study was to document patients’ knowledge, attitudes and practices (KAP) regarding the pandemic influenza A (H1N1) and its prevention. We performed a cross-sectional study on knowledge, attitudes and practices (KAP) on preventive measures of Influenza A (H1N1) involving 322 patients attending Klinik Kesihatan Jinjang, a primary health care clinic in Kuala Lumpur, Malaysia from May 10 to 26, 2010 using a face to face interview with a structured pre-tested questionnaire. The majority of the respondents were females (56.8%), Malays (43.2%) aged between 18-27 years old (28.9%). There were significant association between knowledge on the complication of H1N1, effectiveness of the treatment, preventive measures of Influenza A (H1N1) and race (p<0.001) and educational level (p<0.001). There were also significant associations between attitude scores of these patients and their gender (p=0.03), and educational level (p=0.001). Practice scores related to H1N1 were found to be significantly associated with race (p<0.001) and educational level (p<0.001). The significant associations were observed between knowledge and attitude (p<0.001), knowledge and practices (p<0.001), as well as attitude and practices related to H1N1 (p<0.001). Knowledge has a crucial effect on patients’ attitude and practice particularly in a pandemic spread. So health policy makers should attempt to disseminate information about preventive measures to community in order to improve their preventive practices during pandemics.",2012 Mar 1,"['Latiff, Latiffah A', 'Parhizkar, Saadat', 'Zainuddin, Huda', 'Chun, Goh M', 'Ramli, Mohammad Ali A Rahiman Nur Liyana N', 'Yun, Kerk L']",Glob J Health Sci,,,True
1b482a5e57ac1d83844e7204c907109483603516,PMC,High Prevalence and Putative Lineage Maintenance of Avian Coronaviruses in Scandinavian Waterfowl,http://dx.doi.org/10.1371/journal.pone.0150198,PMC4777420,26938459,CC BY,"Coronaviruses (CoVs) are found in a wide variety of wild and domestic animals, and constitute a risk for zoonotic and emerging infectious disease. In poultry, the genetic diversity, evolution, distribution and taxonomy of some coronaviruses have been well described, but little is known about the features of CoVs in wild birds. In this study we screened 764 samples from 22 avian species of the orders Anseriformes and Charadriiformes in Sweden collected in 2006/2007 for CoV, with an overall CoV prevalence of 18.7%, which is higher than many other wild bird surveys. The highest prevalence was found in the diving ducks—mainly Greater Scaup (Aythya marila; 51.5%)—and the dabbling duck Mallard (Anas platyrhynchos; 19.2%). Sequences from two of the Greater Scaup CoV fell into an infrequently detected lineage, shared only with a Tufted Duck (Aythya fuligula) CoV. Coronavirus sequences from Mallards in this study were highly similar to CoV sequences from the sample species and location in 2011, suggesting long-term maintenance in this population. A single Black-headed Gull represented the only positive sample from the order Charadriiformes. Globally, Anas species represent the largest fraction of avian CoV sequences, and there seems to be no host species, geographical or temporal structure. To better understand the eitiology, epidemiology and ecology of these viruses more systematic surveillance of wild birds and subsequent sequencing of detected CoV is imperative.",2016 Mar 3,"['Wille, Michelle', 'Muradrasoli, Shaman', 'Nilsson, Anna', 'Järhult, Josef D.']",PLoS One,,,True
1d13029ab155210da6e202f8cb5d902d7eabe226,PMC,"Epidemiological study of canine parvovirus infection in and around Bhubaneswar, Odisha, India",http://dx.doi.org/10.14202/vetworld.2015.33-37,PMC4777807,27046992,CC BY,"AIM: An epidemiological study of canine parvovirus infection in dogs in and around Bhubaneswar, Odisha was conducted between December 2012 to March 2013 and prevalence rate was studied on the basis of age, breed, and sex. MATERIALS AND METHODS: A total of 71 fecal samples from suspected diarrheic dogs were collected in sterile phosphate buffer saline (10% W/V) and examined by polymerase chain reaction (PCR) for detection of canine parvo virus infection, followed by epidemiological study in relation to age, breed, and sex. RESULTS: Of 71 samples analyzed, 29 (40.85%) were found to be positive by PCR assay. The infection was higher in Deshi/local breeds (34.48%), followed by German shepherd (17.24%), equal incidences in mixed and Labrador retriever (10.34%), Rottweiler and German spitz showed 6.90% each and finally lower incidences in four breeds (3.45%) such as Dalmatians, Nea politan mastiff, Pug and Great Dane. Age-wise prevalence study revealed the infection being more in the age group of 3-6 months (41.37%), followed by equal incidences of 27.59% in 1-3 months and 6-12 months age group, and a low incidence in age groups above 12 months (3.45%). The incidence was predominantly higher in males (86.21%) than females (13.79%). CONCLUSIONS: The epidemiological analysis revealed that the breed wise prevalence was found to be more in Deshi breeds as compared to others, age groups below 6 months were found to be more prone to parvovirus infection and males were mostly infected.",2015 Jan 9,"['Behera, Monalisa', 'Panda, S. K.', 'Sahoo, P. K.', 'Acharya, A. P.', 'Patra, R. C.', 'Das, Sweta', 'Pati, S.']",Vet World,,,True
8213f353876b2eba6110eae70dae057a2f08b93f,PMC,Long noncoding RNAs (lncRNAs) dynamics evidence immunomodulation during ISAV-Infected Atlantic salmon (Salmo salar),http://dx.doi.org/10.1038/srep22698,PMC4778034,26939752,CC BY,"Despite evidence for participation in the host response to infection, the roles of many long non-coding RNAs (lncRNAs) remain unknown. Therefore, the aims of this study were to identify lncRNAs in Atlantic salmon (Salmo salar) and evaluate their transcriptomic regulation during ISA virus (ISAV) infection, an Orthomyxoviridae virus associated with high mortalities in salmonid aquaculture. Using next-generation sequencing, whole-transcriptome analysis of the Salmo salar response to ISAV infection was performed, identifying 5,636 putative lncRNAs with a mean length of 695 base pairs. The transcriptional modulation evidenced a similar number of differentially expressed lncRNAs in the gills (3,294), head-kidney (3,275), and liver (3,325) over the course of the infection. Moreover, analysis of a subset of these lncRNAs showed the following: (i) Most were similarly regulated in response to ISA virus infection; (ii) The transcript subsets were uniquely modulated in each tissue (gills, liver, and head-kidney); and (iii) A subset of lncRNAs were upregulated for each tissue and time analysed, indicating potential markers for ISAV infection. These findings represent the first discovery of widespread differential expression of lncRNAs in response to virus infection in non-model species, suggesting that lncRNAs could be involved in regulating the host response during ISAV infection.",2016 Mar 4,"['Boltaña, Sebastian', 'Valenzuela-Miranda, Diego', 'Aguilar, Andrea', 'Mackenzie, Simon', 'Gallardo-Escárate, Cristian']",Sci Rep,,,True
08632feec28810500be75d2d1d2a6e287368cade,PMC,Long noncoding RNAs (lncRNAs) dynamics evidence immunomodulation during ISAV-Infected Atlantic salmon (Salmo salar),http://dx.doi.org/10.1038/srep22698,PMC4778034,26939752,CC BY,"Despite evidence for participation in the host response to infection, the roles of many long non-coding RNAs (lncRNAs) remain unknown. Therefore, the aims of this study were to identify lncRNAs in Atlantic salmon (Salmo salar) and evaluate their transcriptomic regulation during ISA virus (ISAV) infection, an Orthomyxoviridae virus associated with high mortalities in salmonid aquaculture. Using next-generation sequencing, whole-transcriptome analysis of the Salmo salar response to ISAV infection was performed, identifying 5,636 putative lncRNAs with a mean length of 695 base pairs. The transcriptional modulation evidenced a similar number of differentially expressed lncRNAs in the gills (3,294), head-kidney (3,275), and liver (3,325) over the course of the infection. Moreover, analysis of a subset of these lncRNAs showed the following: (i) Most were similarly regulated in response to ISA virus infection; (ii) The transcript subsets were uniquely modulated in each tissue (gills, liver, and head-kidney); and (iii) A subset of lncRNAs were upregulated for each tissue and time analysed, indicating potential markers for ISAV infection. These findings represent the first discovery of widespread differential expression of lncRNAs in response to virus infection in non-model species, suggesting that lncRNAs could be involved in regulating the host response during ISAV infection.",2016 Mar 4,"['Boltaña, Sebastian', 'Valenzuela-Miranda, Diego', 'Aguilar, Andrea', 'Mackenzie, Simon', 'Gallardo-Escárate, Cristian']",Sci Rep,,,False
71e40892b5ee0084f5953a80dcae63e68df725d9,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,True
7804648257929e923ff08509b4f1b2c7fd237ab0,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
41f85f8fa21f4d42179b4aaf63f48eb925c479bf,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
4baf7eab1e97a8135fb5b39f1d423bfb0ae4dd8b,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
5c6aa8d966729c4e0ed585493e6e048aa56cf2fc,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
60b5df62d05d96436a83ac05a6e8a6260840c5d8,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
4274448f43e86c8785db478d52788e0912b99f29,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
cb3b8b59e69f6ecea7174599a3f054d61e60c121,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
b0efffeef2a2a7d853e2e5be60e854050ad2ceb6,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
ed63a6725f27494b01ee2bc421e3ebf5bb11da97,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
01c1a483d6c189aa7dc3a833d8a1a80bc063165a,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
794bc58625ed326ad6230e5b1ea2beb5e6f0ec43,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
c7607aa9f76614af859fde6388979f58d5097361,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
24edf60956da0e015f00a5fbbd11fbdbcab16ff3,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
c46022b8376c55d77bf1e504feaa1e6c5e3ed626,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
f6b842b46c9678c37d60556963fc45f97074d56f,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
82273bf92042d6eb6962ab7bb2b4cea4c7a9ab20,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
7f481cf7a2c22bf5d565697c4631ee0da91412aa,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
0c6dfd6796df35e619aa7b8099bd54174415fb52,PMC,"Improved Chiral Separation of (R,S)-Goitrin by SFC: An Application in Traditional Chinese Medicine",http://dx.doi.org/10.1155/2016/5782942,PMC4779522,27022502,CC BY,"Like chemical drugs, research and development of herbal medicine also have a need to resolve enantiomers. To help illustrating the antiviral bioactivity of Isatidis Radix, a widely used traditional Chinese medicine (TCM), supercritical fluid chromatography (SFC) was used for analytical and preparative separation of (R,S)-goitrin, which was reported as the active ingredient of the herbal. Improved resolution was achieved on Chiralpak IC column, using acetonitrile as the organic modifier, representing a tenfold increase in speed, compared to the previous normal phase HPLC (NPLC) method. The newly developed chromatographic method was validated in terms of linearity, precision, limit of detection (LOD), and limit of quantitation (LOQ). Scale-up purification of (R)-goitrin and (S)-goitrin was performed on a preparative column with >90% total recovery. The absolute stereochemical assignment of the purified isomers was determined through optical rotation study. This attempt explored SFC's application in chiral research of traditional Chinese medicine.",2016 Feb 21,"['Nie, Lixing', 'Dai, Zhong', 'Ma, Shuangcheng']",J Anal Methods Chem,,,True
4913c28e343a6cf2f8031799ff3b372e0e873bf5,PMC,Structure of Main Protease from Human Coronavirus NL63: Insights for Wide Spectrum Anti-Coronavirus Drug Design,http://dx.doi.org/10.1038/srep22677,PMC4780191,26948040,CC BY,"First identified in The Netherlands in 2004, human coronavirus NL63 (HCoV-NL63) was found to cause worldwide infections. Patients infected by HCoV-NL63 are typically young children with upper and lower respiratory tract infection, presenting with symptoms including croup, bronchiolitis, and pneumonia. Unfortunately, there are currently no effective antiviral therapy to contain HCoV-NL63 infection. CoV genomes encode an integral viral component, main protease (M(pro)), which is essential for viral replication through proteolytic processing of RNA replicase machinery. Due to the sequence and structural conservation among all CoVs, M(pro) has been recognized as an attractive molecular target for rational anti-CoV drug design. Here we present the crystal structure of HCoV-NL63 M(pro) in complex with a Michael acceptor inhibitor N3. Structural analysis, consistent with biochemical inhibition results, reveals the molecular mechanism of enzyme inhibition at the highly conservative substrate-recognition pocket. We show such molecular target remains unchanged across 30 clinical isolates of HCoV-NL63 strains. Through comparative study with M(pro)s from other human CoVs (including the deadly SARS-CoV and MERS-CoV) and their related zoonotic CoVs, our structure of HCoV-NL63 M(pro) provides critical insight into rational development of wide spectrum antiviral therapeutics to treat infections caused by human CoVs.",2016 Mar 7,"['Wang, Fenghua', 'Chen, Cheng', 'Tan, Wenjie', 'Yang, Kailin', 'Yang, Haitao']",Sci Rep,,,True
6600b6e7a6994f3b8e8d29bbea6b67ba198a36bc,PMC,Structure of Main Protease from Human Coronavirus NL63: Insights for Wide Spectrum Anti-Coronavirus Drug Design,http://dx.doi.org/10.1038/srep22677,PMC4780191,26948040,CC BY,"First identified in The Netherlands in 2004, human coronavirus NL63 (HCoV-NL63) was found to cause worldwide infections. Patients infected by HCoV-NL63 are typically young children with upper and lower respiratory tract infection, presenting with symptoms including croup, bronchiolitis, and pneumonia. Unfortunately, there are currently no effective antiviral therapy to contain HCoV-NL63 infection. CoV genomes encode an integral viral component, main protease (M(pro)), which is essential for viral replication through proteolytic processing of RNA replicase machinery. Due to the sequence and structural conservation among all CoVs, M(pro) has been recognized as an attractive molecular target for rational anti-CoV drug design. Here we present the crystal structure of HCoV-NL63 M(pro) in complex with a Michael acceptor inhibitor N3. Structural analysis, consistent with biochemical inhibition results, reveals the molecular mechanism of enzyme inhibition at the highly conservative substrate-recognition pocket. We show such molecular target remains unchanged across 30 clinical isolates of HCoV-NL63 strains. Through comparative study with M(pro)s from other human CoVs (including the deadly SARS-CoV and MERS-CoV) and their related zoonotic CoVs, our structure of HCoV-NL63 M(pro) provides critical insight into rational development of wide spectrum antiviral therapeutics to treat infections caused by human CoVs.",2016 Mar 7,"['Wang, Fenghua', 'Chen, Cheng', 'Tan, Wenjie', 'Yang, Kailin', 'Yang, Haitao']",Sci Rep,,,False
94fc08607ba07e9f5a0239d27251d4cdcc6bfd9a,PMC,Predominant Bacteria Detected from the Middle Ear Fluid of Children Experiencing Otitis Media: A Systematic Review,http://dx.doi.org/10.1371/journal.pone.0150949,PMC4783106,26953891,CC BY,"BACKGROUND: Otitis media (OM) is amongst the most common childhood diseases and is associated with multiple microbial pathogens within the middle ear. Global and temporal monitoring of predominant bacterial pathogens is important to inform new treatment strategies, vaccine development and to monitor the impact of vaccine implementation to improve progress toward global OM prevention. METHODS: A systematic review of published reports of microbiology of acute otitis media (AOM) and otitis media with effusion (OME) from January, 1970 to August 2014, was performed using PubMed databases. RESULTS: This review confirmed that Streptococcus pneumoniae and Haemophilus influenzae, remain the predominant bacterial pathogens, with S. pneumoniae the predominant bacterium in the majority reports from AOM patients. In contrast, H. influenzae was the predominant bacterium for patients experiencing chronic OME, recurrent AOM and AOM with treatment failure. This result was consistent, even where improved detection sensitivity from the use of polymerase chain reaction (PCR) rather than bacterial culture was conducted. On average, PCR analyses increased the frequency of detection of S. pneumoniae and H. influenzae 3.2 fold compared to culture, whilst Moraxella catarrhalis was 4.5 times more frequently identified by PCR. Molecular methods can also improve monitoring of regional changes in the serotypes and identification frequency of S. pneumoniae and H. influenzae over time or after vaccine implementation, such as after introduction of the 7-valent pneumococcal conjugate vaccine. CONCLUSIONS: Globally, S. pneumoniae and H. influenzae remain the predominant otopathogens associated with OM as identified through bacterial culture; however, molecular methods continue to improve the frequency and accuracy of detection of individual serotypes. Ongoing monitoring with appropriate detection methods for OM pathogens can support development of improved vaccines to provide protection from the complex combination of otopathogens within the middle ear, ultimately aiming to reduce the risk of chronic and recurrent OM in vulnerable populations.",2016 Mar 8,"['Ngo, Chinh C.', 'Massa, Helen M.', 'Thornton, Ruth B.', 'Cripps, Allan W.']",PLoS One,,,True
c07d89610bf10dbbc4124f1a65ffaab6855954ea,PMC,Monitoring Survivability and Infectivity of Porcine Epidemic Diarrhea Virus (PEDv) in the Infected On-Farm Earthen Manure Storages (EMS),http://dx.doi.org/10.3389/fmicb.2016.00265,PMC4783413,27014197,CC BY,"In recent years, porcine epidemic diarrhea virus (PEDv) has caused major epidemics, which has been a burden to North America’s swine industry. Low infectious dose and high viability in the environment are major challenges in eradication of this virus. To further understand the viability of PEDv in the infected manure, we longitudinally monitored survivability and infectivity of PEDv in two open earthen manure storages (EMS; previously referred to as lagoon) from two different infected swine farms identified in the province of Manitoba, Canada. Our study revealed that PEDv could survive up to 9 months in the infected EMS after the initial outbreak in the farm. The viral load varied among different layers of the EMS with an average of 1.1 × 10(5) copies/ml of EMS, independent of EMS temperature and pH. In both studied EMS, the evidence of viral replication was observed through increased viral load in the later weeks of the samplings while there was no new influx of infected manure into the EMS, which was suggestive of presence of potential alternative hosts for PEDv within the EMS. Decreasing infectivity of virus over time irrespective of increased viral load suggested the possibility of PEDv evolution within the EMS and perhaps in the new host that negatively impacted virus infectivity. Viral load in the top layer of the EMS was low and mostly non-infective suggesting that environmental factors, such as UV and sunlight, could diminish the replicability and infectivity of the virus. Thus, frequent agitation of the EMS that could expose virus to UV and sunlight might be a potential strategy for reduction of PEDv load and infectivity in the infected EMS.",2016 Mar 9,"['Tun, Hein M.', 'Cai, Zhangbin', 'Khafipour, Ehsan']",Front Microbiol,,,True
d634751b77c1f304d9dc2a979806013710333b2f,PMC,PEGylated substrates of NSP4 protease: A tool to study protease specificity,http://dx.doi.org/10.1038/srep22856,PMC4783772,26955973,CC BY,"Herein we present the synthesis of a novel type of peptidomimetics composed of repeating diaminopropionic acid residues modified with structurally diverse heterobifunctional polyethylene glycol chains (abbreviated as DAPEG). Based on the developed compounds, a library of fluorogenic substrates was synthesized. Further library deconvolution towards human neutrophil serine protease 4 (NSP4) yielded highly sensitive and selective internally quenched peptidomimetic substrates. In silico analysis of the obtained peptidomimetics revealed the presence of an interaction network with distant subsites located on the enzyme surface.",2016 Mar 9,"['Wysocka, Magdalena', 'Gruba, Natalia', 'Grzywa, Renata', 'Giełdoń, Artur', 'Bąchor, Remigiusz', 'Brzozowski, Krzysztof', 'Sieńczyk, Marcin', 'Dieter, Jenne', 'Szewczuk, Zbigniew', 'Rolka, Krzysztof', 'Lesner, Adam']",Sci Rep,,,True
84e5418129fec4b8872d40a2888a175550c0a6c6,PMC,PEGylated substrates of NSP4 protease: A tool to study protease specificity,http://dx.doi.org/10.1038/srep22856,PMC4783772,26955973,CC BY,"Herein we present the synthesis of a novel type of peptidomimetics composed of repeating diaminopropionic acid residues modified with structurally diverse heterobifunctional polyethylene glycol chains (abbreviated as DAPEG). Based on the developed compounds, a library of fluorogenic substrates was synthesized. Further library deconvolution towards human neutrophil serine protease 4 (NSP4) yielded highly sensitive and selective internally quenched peptidomimetic substrates. In silico analysis of the obtained peptidomimetics revealed the presence of an interaction network with distant subsites located on the enzyme surface.",2016 Mar 9,"['Wysocka, Magdalena', 'Gruba, Natalia', 'Grzywa, Renata', 'Giełdoń, Artur', 'Bąchor, Remigiusz', 'Brzozowski, Krzysztof', 'Sieńczyk, Marcin', 'Dieter, Jenne', 'Szewczuk, Zbigniew', 'Rolka, Krzysztof', 'Lesner, Adam']",Sci Rep,,,True
5fe3454a5e41a3e84b93a71a60d5aad0d81ce840,PMC,Human temperatures for syndromic surveillance in the emergency department: data from the autumn wave of the 2009 swine flu (H1N1) pandemic and a seasonal influenza outbreak,http://dx.doi.org/10.1186/s12873-016-0080-7,PMC4784270,26961277,CC BY,"BACKGROUND: The emergency department (ED) increasingly acts as a gateway to the evaluation and treatment of acute illnesses. Consequently, it has also become a key testing ground for systems that monitor and identify outbreaks of disease. Here, we describe a new technology that automatically collects body temperatures during triage. The technology was tested in an ED as an approach to monitoring diseases that cause fever, such as seasonal flu and some pandemics. METHODS: Temporal artery thermometers that log temperature measurements were placed in a Boston ED and used for initial triage vital signs. Time-stamped measurements were collected from the thermometers to investigate the performance a real-time system would offer. The data were summarized in terms of rates of fever (temperatures ≥100.4 °F [≥38.0 °C]) and were qualitatively compared with regional disease surveillance programs in Massachusetts. RESULTS: From September 2009 through August 2011, 71,865 body temperatures were collected and included in our analysis, 2073 (2.6 %) of which were fevers. The period of study included the autumn–winter wave of the 2009–2010 H1N1 (swine flu) pandemic, during which the weekly incidence of fever reached a maximum of 5.6 %, as well as the 2010–2011 seasonal flu outbreak, during which the maximum weekly incidence of fever was 6.6 %. The periods of peak fever rates corresponded with the periods of regionally elevated flu activity. CONCLUSIONS: Temperature measurements were monitored at triage in the ED over a period of 2 years. The resulting data showed promise as a potential surveillance tool for febrile disease that could complement current disease surveillance systems. Because temperature can easily be measured by non-experts, it might also be suitable for monitoring febrile disease activity in schools, workplaces, and transportation hubs, where many traditional syndromic indicators are impractical. However, the system’s validity and generalizability should be evaluated in additional years and settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12873-016-0080-7) contains supplementary material, which is available to authorized users.",2016 Mar 9,"['Bordonaro, Samantha F.', 'McGillicuddy, Daniel C.', 'Pompei, Francesco', 'Burmistrov, Dmitriy', 'Harding, Charles', 'Sanchez, Leon D.']",BMC Emerg Med,,,True
af98e90951bcd4faddf19d78fc4d228a111323e7,PMC,Human temperatures for syndromic surveillance in the emergency department: data from the autumn wave of the 2009 swine flu (H1N1) pandemic and a seasonal influenza outbreak,http://dx.doi.org/10.1186/s12873-016-0080-7,PMC4784270,26961277,CC BY,"BACKGROUND: The emergency department (ED) increasingly acts as a gateway to the evaluation and treatment of acute illnesses. Consequently, it has also become a key testing ground for systems that monitor and identify outbreaks of disease. Here, we describe a new technology that automatically collects body temperatures during triage. The technology was tested in an ED as an approach to monitoring diseases that cause fever, such as seasonal flu and some pandemics. METHODS: Temporal artery thermometers that log temperature measurements were placed in a Boston ED and used for initial triage vital signs. Time-stamped measurements were collected from the thermometers to investigate the performance a real-time system would offer. The data were summarized in terms of rates of fever (temperatures ≥100.4 °F [≥38.0 °C]) and were qualitatively compared with regional disease surveillance programs in Massachusetts. RESULTS: From September 2009 through August 2011, 71,865 body temperatures were collected and included in our analysis, 2073 (2.6 %) of which were fevers. The period of study included the autumn–winter wave of the 2009–2010 H1N1 (swine flu) pandemic, during which the weekly incidence of fever reached a maximum of 5.6 %, as well as the 2010–2011 seasonal flu outbreak, during which the maximum weekly incidence of fever was 6.6 %. The periods of peak fever rates corresponded with the periods of regionally elevated flu activity. CONCLUSIONS: Temperature measurements were monitored at triage in the ED over a period of 2 years. The resulting data showed promise as a potential surveillance tool for febrile disease that could complement current disease surveillance systems. Because temperature can easily be measured by non-experts, it might also be suitable for monitoring febrile disease activity in schools, workplaces, and transportation hubs, where many traditional syndromic indicators are impractical. However, the system’s validity and generalizability should be evaluated in additional years and settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12873-016-0080-7) contains supplementary material, which is available to authorized users.",2016 Mar 9,"['Bordonaro, Samantha F.', 'McGillicuddy, Daniel C.', 'Pompei, Francesco', 'Burmistrov, Dmitriy', 'Harding, Charles', 'Sanchez, Leon D.']",BMC Emerg Med,,,False
16673eca9ff4c1f57f53126415ad2f89b8cab557,PMC,Human temperatures for syndromic surveillance in the emergency department: data from the autumn wave of the 2009 swine flu (H1N1) pandemic and a seasonal influenza outbreak,http://dx.doi.org/10.1186/s12873-016-0080-7,PMC4784270,26961277,CC BY,"BACKGROUND: The emergency department (ED) increasingly acts as a gateway to the evaluation and treatment of acute illnesses. Consequently, it has also become a key testing ground for systems that monitor and identify outbreaks of disease. Here, we describe a new technology that automatically collects body temperatures during triage. The technology was tested in an ED as an approach to monitoring diseases that cause fever, such as seasonal flu and some pandemics. METHODS: Temporal artery thermometers that log temperature measurements were placed in a Boston ED and used for initial triage vital signs. Time-stamped measurements were collected from the thermometers to investigate the performance a real-time system would offer. The data were summarized in terms of rates of fever (temperatures ≥100.4 °F [≥38.0 °C]) and were qualitatively compared with regional disease surveillance programs in Massachusetts. RESULTS: From September 2009 through August 2011, 71,865 body temperatures were collected and included in our analysis, 2073 (2.6 %) of which were fevers. The period of study included the autumn–winter wave of the 2009–2010 H1N1 (swine flu) pandemic, during which the weekly incidence of fever reached a maximum of 5.6 %, as well as the 2010–2011 seasonal flu outbreak, during which the maximum weekly incidence of fever was 6.6 %. The periods of peak fever rates corresponded with the periods of regionally elevated flu activity. CONCLUSIONS: Temperature measurements were monitored at triage in the ED over a period of 2 years. The resulting data showed promise as a potential surveillance tool for febrile disease that could complement current disease surveillance systems. Because temperature can easily be measured by non-experts, it might also be suitable for monitoring febrile disease activity in schools, workplaces, and transportation hubs, where many traditional syndromic indicators are impractical. However, the system’s validity and generalizability should be evaluated in additional years and settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12873-016-0080-7) contains supplementary material, which is available to authorized users.",2016 Mar 9,"['Bordonaro, Samantha F.', 'McGillicuddy, Daniel C.', 'Pompei, Francesco', 'Burmistrov, Dmitriy', 'Harding, Charles', 'Sanchez, Leon D.']",BMC Emerg Med,,,True
9197060a4f302bde85b29584b40a2c75ba28f837,PMC,Conserved antigenic sites between MERS-CoV and Bat-coronavirus are revealed through sequence analysis,http://dx.doi.org/10.1186/s13029-016-0049-7,PMC4784407,26962326,CC BY,"BACKGROUND: MERS-CoV is a newly emerged human coronavirus reported closely related with HKU4 and HKU5 Bat coronaviruses. Bat and MERS corona-viruses are structurally related. Therefore, it is of interest to estimate the degree of conserved antigenic sites among them. It is of importance to elucidate the shared antigenic-sites and extent of conservation between them to understand the evolutionary dynamics of MERS-CoV. RESULTS: Multiple sequence alignment of the spike (S), membrane (M), enveloped (E) and nucleocapsid (N) proteins was employed to identify the sequence conservation among MERS and Bat (HKU4, HKU5) coronaviruses. We used various in silico tools to predict the conserved antigenic sites. We found that MERS-CoV shared 30 % of its S protein antigenic sites with HKU4 and 70 % with HKU5 bat-CoV. Whereas 100 % of its E, M and N protein’s antigenic sites are found to be conserved with those in HKU4 and HKU5. CONCLUSION: This sharing suggests that in case of pathogenicity MERS-CoV is more closely related to HKU5 bat-CoV than HKU4 bat-CoV. The conserved epitopes indicates their evolutionary relationship and ancestry of pathogenicity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13029-016-0049-7) contains supplementary material, which is available to authorized users.",2016 Mar 9,"['Sharmin, Refat', 'Islam, Abul B. M. M. K.']",Source Code Biol Med,,,True
be459dd25c7c6092a050c722c69ddd3d34ce0f94,PMC,Characterization and analysis of an infectious bronchitis virus strain isolated from southern China in 2013,http://dx.doi.org/10.1186/s12985-016-0497-3,PMC4784446,26955947,CC BY,"BACKGROUND: Infectious bronchitis is a severe disease caused by infectious bronchitis virus (IBV) that affects fowl flocks worldwide. The understanding of the mechanisms involved in IBV evolution and variation would provide important theoretical basis for prevention and control of the disease in the future. METHODS: IBV strain GD was isolated from southern China in 2013 and the complete genome sequencing and phylogenetic analysis were performed. RESULTS: The genome of approximately 27,680 nt comprised six genes, with insertions and mutations in most of the structural genes. The S1 gene showed the highest identity to strain TW2575/98 isolated in Taiwan, and was distantly related to the H120 vaccine strain. Phylogenetic analysis showed that the S1 gene of strain GD was also related to that of TW-type strains. Recombination analysis indicated that strain GD was a chimera whose putative parental strains belonged to the QX- and TW-type subgroups. CONCLUSIONS: An increasing number of TW-type strains have been isolated from China in recent years, which is in agreement with our findings, suggesting the emergence and increased prevalence of new TW-type strains in southern China.",2016 Mar 9,"['Xu, Gang', 'Liu, Xiao-yu', 'Zhao, Ye', 'Chen, Yang', 'Zhao, Jing', 'Zhang, Guo-zhong']",Virol J,,,True
4f67438d123ec1a0d283496cba0ad18fdc5c8e31,PMC,"Epidemiology, Seasonality and Treatment of Hospitalized Adults and Adolescents with Influenza in Jingzhou, China, 2010-2012",http://dx.doi.org/10.1371/journal.pone.0150713,PMC4784897,26958855,CC0,"BACKGROUND: After the 2009 influenza A (H1N1) pandemic, we conducted hospital-based severe acute respiratory infection (SARI) surveillance in one central Chinese city to assess disease burden attributable to influenza among adults and adolescents. METHODS: We defined an adult SARI case as a hospitalized patient aged ≥ 15 years with temperature ≥38.0°C and at least one of the following: cough, sore throat, tachypnea, difficulty breathing, abnormal breath sounds on auscultation, sputum production, hemoptysis, chest pain, or chest radiograph consistent with pneumonia. For each enrolled SARI case-patient, we completed a standardized case report form, and collected a nasopharyngeal swab within 24 hours of admission. Specimens were tested for influenza viruses by real-time reverse transcription polymerase chain reaction (rRT-PCR). We analyzed data from adult SARI cases in four hospitals in Jingzhou, China from April 2010 to April 2012. RESULTS: Of 1,790 adult SARI patients enrolled, 40% were aged ≥ 65 years old. The median duration of hospitalization was 9 days. Nearly all were prescribed antibiotics during their hospitalization, less than 1% were prescribed oseltamivir, and 28% were prescribed corticosteroids. Only 0.1% reported receiving influenza vaccination in the past year. Of 1,704 samples tested, 16% were positive for influenza. Influenza activity in all age groups showed winter-spring and summer peaks. Influenza-positive patients had a longer duration from illness onset to hospitalization and a shorter duration from hospital admission to discharge or death compared to influenza negative SARI patients. CONCLUSIONS: There is substantial burden of influenza-associated SARI hospitalizations in Jingzhou, China, especially among older adults. More effective promotion of annual seasonal influenza vaccination and timely oseltamivir treatment among high risk groups may improve influenza prevention and control in China.",2016 Mar 9,"['Zheng, Jiandong', 'Huo, Xixiang', 'Huai, Yang', 'Xiao, Lin', 'Jiang, Hui', 'Klena, John', 'Greene, Carolyn M.', 'Xing, Xuesen', 'Huang, Jigui', 'Liu, Shali', 'Peng, Youxing', 'Yang, Hui', 'Luo, Jun', 'Peng, Zhibin', 'Liu, Linlin', 'Chen, Maoyi', 'Chen, Hui', 'Zhang, Yuzhi', 'Huang, Danqin', 'Guan, Xuhua', 'Feng, Luzhao', 'Zhan, Faxian', 'Hu, Dale J.', 'Varma, Jay K.', 'Yu, Hongjie']",PLoS One,,,True
5306d1e54bdb040fea797ee3edbefe867ac400f5,PMC,Phylogenetic evidence for intratypic recombinant events in a novel human adenovirus C that causes severe acute respiratory infection in children,http://dx.doi.org/10.1038/srep23014,PMC4785336,26960434,CC BY,"Human adenoviruses (HAdVs) are prevalent in hospitalized children with severe acute respiratory infection (SARI). Here, we report a unique recombinant HAdV strain (CBJ113) isolated from a HAdV-positive child with SARI. The whole-genome sequence was determined using Sanger sequencing and high-throughput sequencing. A phylogenetic analysis of the complete genome indicated that the CBJ113 strain shares a common origin with HAdV-C2, HAdV-C6, HAdV-C1, HAdV-C5, and HAdV-C57 and formed a novel subclade on the same branch as other HAdV-C subtypes. BootScan and single nucleotide polymorphism analyses showed that the CBJ113 genome has an intra-subtype recombinant structure and comprises gene regions mainly originating from two circulating viral strains: HAdV-1 and HAdV-2. The parental penton base, pVI, and DBP genes of the recombinant strain clustered with the HAdV-1 prototype strain, and the E1B, hexon, fiber, and 100 K genes of the recombinant clustered within the HAdV-2 subtype, meanwhile the E4orf1 and DNA polymerase genes of the recombinant shared the greatest similarity with those of HAdV-5 and HAdV-6, respectively. All of these findings provide insight into our understanding of the dynamics of the complexity of the HAdV-C epidemic. More extensive studies should address the pathogenicity and clinical characteristics of the novel recombinant.",2016 Mar 10,"['Wang, Yanqun', 'Li, Yamin', 'Lu, Roujian', 'Zhao, Yanjie', 'Xie, Zhengde', 'Shen, Jun', 'Tan, Wenjie']",Sci Rep,,,True
3557b5b8c5052a1f7fbb18130ace9427201e0fe4,PMC,Viruses as Sole Causative Agents of Severe Acute Respiratory Tract Infections in Children,http://dx.doi.org/10.1371/journal.pone.0150776,PMC4786225,26964038,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) and influenza A viruses are known to cause severe acute respiratory tract infections (SARIs) in children. For other viruses like human rhinoviruses (HRVs) this is less well established. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections. OBJECTIVE: The study aims at identifying viruses that may cause SARI in children in the absence of viral and bacterial co-infections, at identifying disease characteristics associated with these single virus infections, and at identifying a possible correlation between viral loads and disease severities. STUDY DESIGN: Between April 2007 and March 2012, we identified children (<18 year) with or without a medical history, admitted to our paediatric intensive care unit (PICU) with SARI or to the medium care (MC) with an acute respiratory tract infection (ARTI) (controls). Data were extracted from the clinical and laboratory databases of our tertiary care paediatric hospital. Patient specimens were tested for fifteen respiratory viruses with real-time reverse transcriptase PCR assays and we selected patients with a single virus infection only. Typical bacterial co-infections were considered unlikely to have contributed to the PICU or MC admission based on C-reactive protein-levels or bacteriological test results if performed. RESULTS: We identified 44 patients admitted to PICU with SARI and 40 patients admitted to MC with ARTI. Twelve viruses were associated with SARI, ten of which were also associated with ARTI in the absence of typical bacterial and viral co-infections, with RSV and HRV being the most frequent causes. Viral loads were not different between PICU-SARI patients and MC-ARTI patients. CONCLUSION: Both SARI and ARTI may be caused by single viral pathogens in previously healthy children as well as in children with a medical history. No relationship between viral load and disease severity was identified.",2016 Mar 10,"['Moesker, Fleur M.', 'van Kampen, Jeroen J. A.', 'van Rossum, Annemarie M. C.', 'de Hoog, Matthijs', 'Koopmans, Marion P. G.', 'Osterhaus, Albert D. M. E.', 'Fraaij, Pieter L. A.']",PLoS One,,,True
af0300839dd55d28a98c56af294244dcb5811000,PMC,Viruses as Sole Causative Agents of Severe Acute Respiratory Tract Infections in Children,http://dx.doi.org/10.1371/journal.pone.0150776,PMC4786225,26964038,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) and influenza A viruses are known to cause severe acute respiratory tract infections (SARIs) in children. For other viruses like human rhinoviruses (HRVs) this is less well established. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections. OBJECTIVE: The study aims at identifying viruses that may cause SARI in children in the absence of viral and bacterial co-infections, at identifying disease characteristics associated with these single virus infections, and at identifying a possible correlation between viral loads and disease severities. STUDY DESIGN: Between April 2007 and March 2012, we identified children (<18 year) with or without a medical history, admitted to our paediatric intensive care unit (PICU) with SARI or to the medium care (MC) with an acute respiratory tract infection (ARTI) (controls). Data were extracted from the clinical and laboratory databases of our tertiary care paediatric hospital. Patient specimens were tested for fifteen respiratory viruses with real-time reverse transcriptase PCR assays and we selected patients with a single virus infection only. Typical bacterial co-infections were considered unlikely to have contributed to the PICU or MC admission based on C-reactive protein-levels or bacteriological test results if performed. RESULTS: We identified 44 patients admitted to PICU with SARI and 40 patients admitted to MC with ARTI. Twelve viruses were associated with SARI, ten of which were also associated with ARTI in the absence of typical bacterial and viral co-infections, with RSV and HRV being the most frequent causes. Viral loads were not different between PICU-SARI patients and MC-ARTI patients. CONCLUSION: Both SARI and ARTI may be caused by single viral pathogens in previously healthy children as well as in children with a medical history. No relationship between viral load and disease severity was identified.",2016 Mar 10,"['Moesker, Fleur M.', 'van Kampen, Jeroen J. A.', 'van Rossum, Annemarie M. C.', 'de Hoog, Matthijs', 'Koopmans, Marion P. G.', 'Osterhaus, Albert D. M. E.', 'Fraaij, Pieter L. A.']",PLoS One,,,False
8137902f849f58d6a3be9061630529af49f8ed98,PMC,Viruses as Sole Causative Agents of Severe Acute Respiratory Tract Infections in Children,http://dx.doi.org/10.1371/journal.pone.0150776,PMC4786225,26964038,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) and influenza A viruses are known to cause severe acute respiratory tract infections (SARIs) in children. For other viruses like human rhinoviruses (HRVs) this is less well established. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections. OBJECTIVE: The study aims at identifying viruses that may cause SARI in children in the absence of viral and bacterial co-infections, at identifying disease characteristics associated with these single virus infections, and at identifying a possible correlation between viral loads and disease severities. STUDY DESIGN: Between April 2007 and March 2012, we identified children (<18 year) with or without a medical history, admitted to our paediatric intensive care unit (PICU) with SARI or to the medium care (MC) with an acute respiratory tract infection (ARTI) (controls). Data were extracted from the clinical and laboratory databases of our tertiary care paediatric hospital. Patient specimens were tested for fifteen respiratory viruses with real-time reverse transcriptase PCR assays and we selected patients with a single virus infection only. Typical bacterial co-infections were considered unlikely to have contributed to the PICU or MC admission based on C-reactive protein-levels or bacteriological test results if performed. RESULTS: We identified 44 patients admitted to PICU with SARI and 40 patients admitted to MC with ARTI. Twelve viruses were associated with SARI, ten of which were also associated with ARTI in the absence of typical bacterial and viral co-infections, with RSV and HRV being the most frequent causes. Viral loads were not different between PICU-SARI patients and MC-ARTI patients. CONCLUSION: Both SARI and ARTI may be caused by single viral pathogens in previously healthy children as well as in children with a medical history. No relationship between viral load and disease severity was identified.",2016 Mar 10,"['Moesker, Fleur M.', 'van Kampen, Jeroen J. A.', 'van Rossum, Annemarie M. C.', 'de Hoog, Matthijs', 'Koopmans, Marion P. G.', 'Osterhaus, Albert D. M. E.', 'Fraaij, Pieter L. A.']",PLoS One,,,False
4d754b08444d19e6df8559afad357bb13be89bd8,PMC,Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis,http://dx.doi.org/10.1371/journal.pone.0150861,PMC4786309,26963721,CC BY,"BACKGROUND: There is evidence to support a role for angiotensin (Ang) 1–7 in reducing the activity of inflammatory signaling molecules such as MAPK, PKC and SRC. Enhanced angiotensin converting enzyme 2 (ACE2) expression has been observed in patients with inflammatory bowel disease (IBD) suggesting a role in its pathogenesis, prompting this study. METHODS: The colonic expression/activity profile of ACE2, Ang 1–7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence. The effect of either exogenous administration of Ang 1–7 or pharmacological inhibition of its function (by A779 treatment) was determined using the mouse dextran sulfate sodium model. RESULTS: Enhanced colonic expression of ACE2, Ang1-7 and MAS1-R was observed post-colitis induction. Daily Ang 1–7 treatment (0.01–0.06 mg/kg) resulted in significant amelioration of DSS-induced colitis. In contrast, daily administration of A779 significantly worsened features of colitis. Colitis-associated phosphorylation of p38, ERK1/2 and Akt was reduced by Ang 1–7 treatment. CONCLUSION: Our results indicate important anti-inflammatory actions of Ang 1–7 in the pathogenesis of IBD, which may provide a future therapeutic strategy to control the disease progression.",2016 Mar 10,"['Khajah, Maitham A.', 'Fateel, Maryam M.', 'Ananthalakshmi, Kethireddy V.', 'Luqmani, Yunus A.']",PLoS One,,,True
9a4eb1665b578ba6744d7c2a62775379f6fcfc00,PMC,Understanding Spatio-Temporal Variability in the Reproduction Ratio of the Bluetongue (BTV-1) Epidemic in Southern Spain (Andalusia) in 2007 Using Epidemic Trees,http://dx.doi.org/10.1371/journal.pone.0151151,PMC4786328,26963397,CC BY,"Andalusia (Southern Spain) is considered one of the main routes of introduction of bluetongue virus (BTV) into Europe, evidenced by a devastating epidemic caused by BTV-1 in 2007. Understanding the pattern and the drivers of BTV-1 spread in Andalusia is critical for effective detection and control of future epidemics. A long-standing metric for quantifying the behaviour of infectious diseases is the case-reproduction ratio (R(t)), defined as the average number of secondary cases arising from a single infected case at time t (for t>0). Here we apply a method using epidemic trees to estimate the between-herd case reproduction ratio directly from epidemic data allowing the spatial and temporal variability in transmission to be described. We then relate this variability to predictors describing the hosts, vectors and the environment to better understand why the epidemic spread more quickly in some regions or periods. The R(t) value for the BTV-1 epidemic in Andalusia peaked in July at 4.6, at the start of the epidemic, then decreased to 2.2 by August, dropped below 1 by September (0.8), and by October it had decreased to 0.02. BTV spread was the consequence of both local transmission within established disease foci and BTV expansion to distant new areas (i.e. new foci), which resulted in a high variability in BTV transmission, not only among different areas, but particularly through time, which suggests that general control measures applied at broad spatial scales are unlikely to be effective. This high variability through time was probably due to the impact of temperature on BTV transmission, as evidenced by a reduction in the value of R(t) by 0.0041 for every unit increase (day) in the extrinsic incubation period (EIP), which is itself directly dependent on temperature. Moreover, within the range of values at which BTV-1 transmission occurred in Andalusia (20.6°C to 29.5°C) there was a positive correlation between temperature and R(t) values, although the relationship was not linear, probably as a result of the complex relationship between temperature and the different parameters affecting BTV transmission. R(t) values for BTV-1 in Andalusia fell below the threshold of 1 when temperatures dropped below 21°C, a much higher threshold than that reported in other BTV outbreaks, such as the BTV-8 epidemic in Northern Europe. This divergence may be explained by differences in the adaptation to temperature of the main vectors of the BTV-1 epidemic in Andalusia (Culicoides imicola) compared those of the BTV-8 epidemic in Northern Europe (Culicoides obsoletus). Importantly, we found that BTV transmission (R(t) value) increased significantly in areas with higher densities of sheep. Our analysis also established that control of BTV-1 in Andalusia was complicated by the simultaneous establishment of several distant foci at the start of the epidemic, which may have been caused by several independent introductions of infected vectors from the North of Africa. We discuss the implications of these findings for BTV surveillance and control in this region of Europe.",2016 Mar 10,"['Napp, S.', 'Allepuz, A.', 'Purse, B. V.', 'Casal, J.', 'García-Bocanegra, I.', 'Burgin, L. E.', 'Searle, K. R.']",PLoS One,,,True
3bd56ae4a76caf910da9be6266e18b74308364b6,PMC,Severe Community-Acquired Pneumonia Caused by Human Adenovirus in Immunocompetent Adults: A Multicenter Case Series,http://dx.doi.org/10.1371/journal.pone.0151199,PMC4788423,26967644,CC BY,"BACKGROUND: Severe community-acquired pneumonia (CAP) caused by human adenovirus (HAdV), especially HAdV type 55 (HAdV-55) in immunocompetent adults has raised increasing concerns. Clinical knowledge of severe CAP and acute respiratory distress syndrome induced by HAdV-55 is still limited, though the pathogen has been fully characterized by whole-genome sequencing. METHODS: We conducted a multicentre retrospective review of all consecutive patients with severe CAP caused by HAdV in immunocompetent adults admitted to the Emergency Department Intensive Care Unit of two hospitals in Northern China between February 2012 and April 2014. Clinical, laboratory, radiological characteristics, treatments and outcomes of these patients were collected and analyzed. RESULTS: A total of 15 consecutive severe CAP patients with laboratory-confirmed adenovirus infections were included. The median age was 30 years and all cases were identified during the winter and spring seasons. HAdV-55 was the most frequently (11/15) detected HAdV type. Persistent high fever, cough and rapid progression of dyspnea were typically reported in these patients. Significantly increased pneumonia severity index (PSI), respiratory rate, and lower PaO(2)/FiO(2), hypersensitive CRP were reported in non-survivors compared to survivors (P = 0.013, 0.022, 0.019 and 0.026, respectively). The rapid development of bilateral consolidations within 10 days after illness onset were the most common radiographic finding, usually accompanied by adjacent ground glass opacities and pleural effusions. Total mortality was 26.7% in this study. Corticosteroids were prescribed to 14 patients in this report, but the utilization rate between survivors and non-survivors was not significant. CONCLUSIONS: HAdV and the HAdV-55 sub-type play an important role among viral pneumonia pathogens in hospitalized immunocompetent adults in Northern China. HAdV should be tested in severe CAP patients with negative bacterial cultures and a lack of response to antibiotic treatment, even if radiologic imaging and clinical presentation initially suggest bacterial pneumonia.",2016 Mar 11,"['Tan, Dingyu', 'Zhu, Huadong', 'Fu, Yangyang', 'Tong, Fei', 'Yao, Dongqi', 'Walline, Joseph', 'Xu, Jun', 'Yu, Xuezhong']",PLoS One,,,True
430903f42d10ae8f5729df9a61e75e2d6dc09f65,PMC,Modeling the transboundary risk of feed ingredients contaminated with porcine epidemic diarrhea virus,http://dx.doi.org/10.1186/s12917-016-0674-z,PMC4788872,26968372,CC BY,"BACKGROUND: This study describes a model developed to evaluate the transboundary risk of PEDV-contaminated swine feed ingredients and the effect of two mitigation strategies during a simulated transport event from China to the US. RESULTS: Ingredients imported to the USA from China, including organic & conventional soybeans and meal, lysine hydrochloride, D-L methionine, tryptophan, Vitamins A, D & E, choline, carriers (rice hulls, corn cobs) and feed grade tetracycline, were inoculated with PEDV. Control ingredients, and treatments (ingredients plus a liquid antimicrobial (SalCURB, Kemin Industries (LA) or a 2 % custom medium chain fatty acid blend (MCFA)) were tested. The model ran for 37 days, simulating transport of cargo from Beijing, China to Des Moines, IA, US from December 23, 2012 to January 28, 2013. To mimic conditions on land and sea, historical temperature and percent relative humidity (% RH) data were programmed into an environmental chamber which stored all containers. To evaluate PEDV viability over time, ingredients were organized into 1 of 4 batches of samples, each batch representing a specific segment of transport. Batch 1 (segment 1) simulated transport of contaminated ingredients from manufacturing plants in Beijing (day 1 post-contamination (PC)). Batch 2 (segments 1 and 2) simulated manufacturing and delivery to Shanghai, including time in Anquing terminal awaiting shipment (days 1–8 PC). Batch 3 (segments 1, 2 and 3) represented time in China, the crossing of the Pacific and entry to the US at the San Francisco, CA terminal (day 1–27 PC). Batch 4 (segments 1–4) represented the previous events, including transport to Des Moines, IA (days 1–37 PC). Across control (non-treated) ingredients, viable PEDV was detected in soybean meal (organic and conventional), Vitamin D, lysine hydrochloride and choline chloride. In contrast, viable PEDV was not detected in any samples treated with LA or MCFA. CONCLUSIONS: These results demonstrate the ability of PEDV to survive in a subset of feed ingredients using a model simulating shipment from China to the US. This is proof of concept suggesting that contaminated feed ingredients could serve as transboundary risk factors for PEDV, along with the identification of effective mitigation options.",2016 Mar 12,"['Dee, Scott', 'Neill, Casey', 'Singrey, Aaron', 'Clement, Travis', 'Cochrane, Roger', 'Jones, Cassandra', 'Patterson, Gilbert', 'Spronk, Gordon', 'Christopher-Hennings, Jane', 'Nelson, Eric']",BMC Vet Res,,,True
35cd13c57dc46df01a1cae4ee1edbff7774cfe9b,PMC,Cytosolic Innate Immune Sensing and Signaling upon Infection,http://dx.doi.org/10.3389/fmicb.2016.00313,PMC4789553,27014235,CC BY,"Cytosolic sensing of pathogens is essential to a productive immune response. Recent reports have emphasized the importance of signaling platforms emanating from organelles and cytosolic sensors, particularly during the response to intracellular pathogens. Here, we highlight recent discoveries identifying the key mediators of nucleic acid and cyclic nucleotide sensing and discuss their importance in host defense. This review will also cover strategies evolved by pathogens to manipulate these pathways.",2016 Mar 14,"['Radoshevich, Lilliana', 'Dussurget, Olivier']",Front Microbiol,,,True
769d042233efa89198582de95656f0bb2198f379,PMC,Monitoring the Spread of Swine Enteric Coronavirus Diseases in the United States in the Absence of a Regulatory Framework,http://dx.doi.org/10.3389/fvets.2016.00018,PMC4789556,27014703,CC BY,"The reporting and monitoring of swine enteric coronavirus diseases (SECD), including porcine epidemic diarrhea virus and porcine delta coronavirus, in the United States have been challenging because of the initial absence of a regulatory framework and the emerging nature of these diseases. The National Animal Health Laboratory Network, the Emergency Management and Response System, and the Swine Health Monitoring Project were used to monitor the disease situation between May 2013 and March 2015. Important differences existed between and among them in terms of nature and extent of reporting. Here, we assess the implementation of these systems from different perspectives, including a description and comparison of collected data, disease metrics, usefulness, simplicity, flexibility, acceptability, representativeness, timeliness, and stability. This assessment demonstrates the limitations that the absence of premises identification imposes on certain animal health surveillance and response databases, and the importance of federally regulated frameworks in collecting accurate information in a timely manner. This study also demonstrates the value that the voluntary and producer-organized systems may have in monitoring emerging diseases. The results from all three data sources help to establish the baseline information on SECD epidemiological dynamics after almost 3 years of disease occurrence in the country.",2016 Mar 14,"['Perez, Andres M.', 'Alba, Anna', 'Goede, Dane', 'McCluskey, Brian', 'Morrison, Robert']",Front Vet Sci,,,True
56fb26305485a7d9c7844df6b25e30c8f1af4363,PMC,Epidemiological investigation of the 119th confirmed Middle East Respiratory Syndrome coronavirus case with an indefinite mode of transmission during the Pyeongtaek outbreak in Korea,http://dx.doi.org/10.4178/epih/e2015054,PMC4789606,26971695,CC BY,"Since the first case was diagnosed on May 20, 2015, there were 186 confirmed cases of Middle East Respiratory Syndrome (MERS) until the end of outbreak in South Korea. Although medical institutions were the most identifiable sources of MERS transmission in South Korea, similar to other countries, in-depth epidemiological investigation was required for some confirmed cases with indefinite contact history or hospital visit records. The subject of epidemiological investigation in the present study was a 35 year-old male patient diagnosed with MERS (#119) who lived in Asan-city and worked in Pyeongtaek-city. Various potential sources of transmission were carefully investigated. While he could have been exposed to MERS through a friend from Saudi Arabia or confirmed MERS cases in his workplace, neighboring areas, and medical institutions, as well as contacts in his home, the chances of transmission were low; however, the potential for transmission through his local community could not be excluded. Practically, it was difficult to determine the modes of transmission for all outbreak cases in communicable disease that occurred in this short period of time. The investigation to identify the mode of transmission in this case was ultimately unsuccessful. However, the various data collected and analyzed to reveal modes of transmission provided detailed information that could not be collected using only interview surveys.",2015 Dec 10,"['Choi, Jong Hyuk', 'Yoo, Byoungin', 'Lee, Soon Young', 'Lee, Eun Gyu', 'Ki, Moran', 'Lee, Woncheol', 'Jung, Jong Rak', 'Chang, Kyujin']",Epidemiol Health,,,True
6468e66c83046c44f33276aaf429c82fd2ef8cd0,PMC,Epidemiological investigation of the 119th confirmed Middle East Respiratory Syndrome coronavirus case with an indefinite mode of transmission during the Pyeongtaek outbreak in Korea,http://dx.doi.org/10.4178/epih/e2015054,PMC4789606,26971695,CC BY,"Since the first case was diagnosed on May 20, 2015, there were 186 confirmed cases of Middle East Respiratory Syndrome (MERS) until the end of outbreak in South Korea. Although medical institutions were the most identifiable sources of MERS transmission in South Korea, similar to other countries, in-depth epidemiological investigation was required for some confirmed cases with indefinite contact history or hospital visit records. The subject of epidemiological investigation in the present study was a 35 year-old male patient diagnosed with MERS (#119) who lived in Asan-city and worked in Pyeongtaek-city. Various potential sources of transmission were carefully investigated. While he could have been exposed to MERS through a friend from Saudi Arabia or confirmed MERS cases in his workplace, neighboring areas, and medical institutions, as well as contacts in his home, the chances of transmission were low; however, the potential for transmission through his local community could not be excluded. Practically, it was difficult to determine the modes of transmission for all outbreak cases in communicable disease that occurred in this short period of time. The investigation to identify the mode of transmission in this case was ultimately unsuccessful. However, the various data collected and analyzed to reveal modes of transmission provided detailed information that could not be collected using only interview surveys.",2015 Dec 10,"['Choi, Jong Hyuk', 'Yoo, Byoungin', 'Lee, Soon Young', 'Lee, Eun Gyu', 'Ki, Moran', 'Lee, Woncheol', 'Jung, Jong Rak', 'Chang, Kyujin']",Epidemiol Health,,,False
4e6e76a1940fbfadea1d88bbcbfe4f1554f7719b,PMC,Identification of novel RNA secondary structures within the hepatitis C virus genome reveals a cooperative involvement in genome packaging,http://dx.doi.org/10.1038/srep22952,PMC4789732,26972799,CC BY,"The specific packaging of the hepatitis C virus (HCV) genome is hypothesised to be driven by Core-RNA interactions. To identify the regions of the viral genome involved in this process, we used SELEX (systematic evolution of ligands by exponential enrichment) to identify RNA aptamers which bind specifically to Core in vitro. Comparison of these aptamers to multiple HCV genomes revealed the presence of a conserved terminal loop motif within short RNA stem-loop structures. We postulated that interactions of these motifs, as well as sub-motifs which were present in HCV genomes at statistically significant levels, with the Core protein may drive virion assembly. We mutated 8 of these predicted motifs within the HCV infectious molecular clone JFH-1, thereby producing a range of mutant viruses predicted to possess altered RNA secondary structures. RNA replication and viral titre were unaltered in viruses possessing only one mutated structure. However, infectivity titres were decreased in viruses possessing a higher number of mutated regions. This work thus identified multiple novel RNA motifs which appear to contribute to genome packaging. We suggest that these structures act as cooperative packaging signals to drive specific RNA encapsidation during HCV assembly.",2016 Mar 14,"['Stewart, H.', 'Bingham, R.J.', 'White, S. J.', 'Dykeman, E. C.', 'Zothner, C.', 'Tuplin, A. K.', 'Stockley, P. G.', 'Twarock, R.', 'Harris, M.']",Sci Rep,,,True
399cef5a5c8ca96a0ac33ee31dec722eac145a7b,PMC,FLDS: A Comprehensive dsRNA Sequencing Method for Intracellular RNA Virus Surveillance,http://dx.doi.org/10.1264/jsme2.ME15171,PMC4791113,26877136,CC BY,"Knowledge of the distribution and diversity of RNA viruses is still limited in spite of their possible environmental and epidemiological impacts because RNA virus-specific metagenomic methods have not yet been developed. We herein constructed an effective metagenomic method for RNA viruses by targeting long double-stranded (ds)RNA in cellular organisms, which is a hallmark of infection, or the replication of dsRNA and single-stranded (ss)RNA viruses, except for retroviruses. This novel dsRNA targeting metagenomic method is characterized by an extremely high recovery rate of viral RNA sequences, the retrieval of terminal sequences, and uniform read coverage, which has not previously been reported in other metagenomic methods targeting RNA viruses. This method revealed a previously unidentified viral RNA diversity of more than 20 complete RNA viral genomes including dsRNA and ssRNA viruses associated with an environmental diatom colony. Our approach will be a powerful tool for cataloging RNA viruses associated with organisms of interest.",2016 Mar 13,"['Urayama, Syun-ichi', 'Takaki, Yoshihiro', 'Nunoura, Takuro']",Microbes Environ,,,True
97e8e782d5c99ab2e4fef7e8af54d77677ba6e3e,PMC,FLDS: A Comprehensive dsRNA Sequencing Method for Intracellular RNA Virus Surveillance,http://dx.doi.org/10.1264/jsme2.ME15171,PMC4791113,26877136,CC BY,"Knowledge of the distribution and diversity of RNA viruses is still limited in spite of their possible environmental and epidemiological impacts because RNA virus-specific metagenomic methods have not yet been developed. We herein constructed an effective metagenomic method for RNA viruses by targeting long double-stranded (ds)RNA in cellular organisms, which is a hallmark of infection, or the replication of dsRNA and single-stranded (ss)RNA viruses, except for retroviruses. This novel dsRNA targeting metagenomic method is characterized by an extremely high recovery rate of viral RNA sequences, the retrieval of terminal sequences, and uniform read coverage, which has not previously been reported in other metagenomic methods targeting RNA viruses. This method revealed a previously unidentified viral RNA diversity of more than 20 complete RNA viral genomes including dsRNA and ssRNA viruses associated with an environmental diatom colony. Our approach will be a powerful tool for cataloging RNA viruses associated with organisms of interest.",2016 Mar 13,"['Urayama, Syun-ichi', 'Takaki, Yoshihiro', 'Nunoura, Takuro']",Microbes Environ,,,False
77ce5438ade47650db78180cf5f4612db3e31c7b,PMC,"Dr. Wu Lien Teh, plague fighter and father of the Chinese public health system",http://dx.doi.org/10.1007/s13238-015-0238-1,PMC4791421,26825808,CC BY,,2016 Mar 29,"['Ma, Zhongliang', 'Li, Yanli']",Protein Cell,,,True
08741b63c08d63c1a86dd3ef3ce3d1bfd39e560b,PMC,"Dissection and integration of the autophagy signaling network initiated by bluetongue virus infection: crucial candidates ERK1/2, Akt and AMPK",http://dx.doi.org/10.1038/srep23130,PMC4791558,26976147,CC BY,"Bluetongue virus (BTV), a complex double-stranded segmented RNA virus, has been found to initiate cellular autophagy for its own benefit. Here, with a view to understanding the underlying mechanisms, we first systematically dissected the exact signaling network in BTV-induced autophagy. We found that the activity of mTOR, a crucial pivot, was inhibited by BTV1 infection, subsequently leading to downstream p70S6K suppression and autophagy initiation. We then explored the upstream regulators of mTOR and analyzed their activities via a series of assays. We found BTV1-induced autophagy to be independent of the ERK1/2 signaling pathway. However, the BTV1-induced inhibition of PI3K/Akt was found to be partially responsible for mTOR inactivation and subsequent autophagy initiation. Furthermore, we found unexpectedly that AMPK seemed to play a more important role in BTV1-induced autophagy. Elevated [Ca(2+)](cyto)-mediated activation of CaMKKβ exactly managed the activation of AMPK, which then positively regulated autophagy through suppressing mTOR. We must emphasize that TSC2 is a fatal mediator between upstream Akt or AMPK and downstream mTOR through its phosphorylation. Taken together, our data suggested that the BTV1-induced inhibition of the Akt-TSC2-mTOR pathway and the upregulation of the AMPK-TSC2-mTOR pathway both contributed to autophagy initiation and further favored virus replication.",2016 Mar 15,"['Lv, Shuang', 'Xu, Qing-Yuan', 'Sun, En-Cheng', 'Zhang, Ji-Kai', 'Wu, Dong-Lai']",Sci Rep,,,True
571625547b1603db0ad2f114822184a61f8e1b54,PMC,"Dissection and integration of the autophagy signaling network initiated by bluetongue virus infection: crucial candidates ERK1/2, Akt and AMPK",http://dx.doi.org/10.1038/srep23130,PMC4791558,26976147,CC BY,"Bluetongue virus (BTV), a complex double-stranded segmented RNA virus, has been found to initiate cellular autophagy for its own benefit. Here, with a view to understanding the underlying mechanisms, we first systematically dissected the exact signaling network in BTV-induced autophagy. We found that the activity of mTOR, a crucial pivot, was inhibited by BTV1 infection, subsequently leading to downstream p70S6K suppression and autophagy initiation. We then explored the upstream regulators of mTOR and analyzed their activities via a series of assays. We found BTV1-induced autophagy to be independent of the ERK1/2 signaling pathway. However, the BTV1-induced inhibition of PI3K/Akt was found to be partially responsible for mTOR inactivation and subsequent autophagy initiation. Furthermore, we found unexpectedly that AMPK seemed to play a more important role in BTV1-induced autophagy. Elevated [Ca(2+)](cyto)-mediated activation of CaMKKβ exactly managed the activation of AMPK, which then positively regulated autophagy through suppressing mTOR. We must emphasize that TSC2 is a fatal mediator between upstream Akt or AMPK and downstream mTOR through its phosphorylation. Taken together, our data suggested that the BTV1-induced inhibition of the Akt-TSC2-mTOR pathway and the upregulation of the AMPK-TSC2-mTOR pathway both contributed to autophagy initiation and further favored virus replication.",2016 Mar 15,"['Lv, Shuang', 'Xu, Qing-Yuan', 'Sun, En-Cheng', 'Zhang, Ji-Kai', 'Wu, Dong-Lai']",Sci Rep,,,False
bbed3cc036065a43e9da69ad09ce74d487b31c6b,PMC,Knowledge sharing during public health emergencies: from global call to effective implementation,http://dx.doi.org/10.2471/BLT.16.172650,PMC4794312,27034513,CC BY,,2016 Apr 1,"['Delaunay, Sophie', 'Kahn, Patricia', 'Tatay, Mercedes', 'Liu, Joanne']",Bull World Health Organ,,,True
f4aa788ab898b28b00ee103e4d4ab24a2c684caf,PMC,Venezuelan Equine Encephalitis Virus Induces Apoptosis through the Unfolded Protein Response Activation of EGR1,http://dx.doi.org/10.1128/JVI.02827-15,PMC4794670,26792742,CC BY,"Venezuelan equine encephalitis virus (VEEV) is a previously weaponized arthropod-borne virus responsible for causing acute and fatal encephalitis in animal and human hosts. The increased circulation and spread in the Americas of VEEV and other encephalitic arboviruses, such as eastern equine encephalitis virus and West Nile virus, underscore the need for research aimed at characterizing the pathogenesis of viral encephalomyelitis for the development of novel medical countermeasures. The host-pathogen dynamics of VEEV Trinidad donkey-infected human astrocytoma U87MG cells were determined by carrying out RNA sequencing (RNA-Seq) of poly(A) and mRNAs. To identify the critical alterations that take place in the host transcriptome following VEEV infection, samples were collected at 4, 8, and 16 h postinfection and RNA-Seq data were acquired using an Ion Torrent PGM platform. Differential expression of interferon response, stress response factors, and components of the unfolded protein response (UPR) was observed. The protein kinase RNA-like endoplasmic reticulum kinase (PERK) arm of the UPR was activated, as the expression of both activating transcription factor 4 (ATF4) and CHOP (DDIT3), critical regulators of the pathway, was altered after infection. Expression of the transcription factor early growth response 1 (EGR1) was induced in a PERK-dependent manner. EGR1(−/−) mouse embryonic fibroblasts (MEFs) demonstrated lower susceptibility to VEEV-induced cell death than isogenic wild-type MEFs, indicating that EGR1 modulates proapoptotic pathways following VEEV infection. The influence of EGR1 is of great importance, as neuronal damage can lead to long-term sequelae in individuals who have survived VEEV infection. IMPORTANCE Alphaviruses represent a group of clinically relevant viruses transmitted by mosquitoes to humans. In severe cases, viral spread targets neuronal tissue, resulting in significant and life-threatening inflammation dependent on a combination of virus-host interactions. Currently there are no therapeutics for infections cause by encephalitic alphaviruses due to an incomplete understanding of their molecular pathogenesis. Venezuelan equine encephalitis virus (VEEV) is an alphavirus that is prevalent in the Americas and that is capable of infecting horses and humans. Here we utilized next-generation RNA sequencing to identify differential alterations in VEEV-infected astrocytes. Our results indicated that the abundance of transcripts associated with the interferon and the unfolded protein response pathways was altered following infection and demonstrated that early growth response 1 (EGR1) contributed to VEEV-induced cell death.",2016 Mar 11,"['Baer, Alan', 'Lundberg, Lindsay', 'Swales, Danielle', 'Waybright, Nicole', 'Pinkham, Chelsea', 'Dinman, Jonathan D.', 'Jacobs, Jonathan L.', 'Kehn-Hall, Kylene']",J Virol,,,True
9301787667eb36e650623c8dc753399f3e1b4b7c,PMC,A Next-Generation Sequencing Data Analysis Pipeline for Detecting Unknown Pathogens from Mixed Clinical Samples and Revealing Their Genetic Diversity,http://dx.doi.org/10.1371/journal.pone.0151495,PMC4795770,26986479,CC BY,"Forty-two cytopathic effect (CPE)-positive isolates were collected from 2008 to 2012. All isolates could not be identified for known viral pathogens by routine diagnostic assays. They were pooled into 8 groups of 5–6 isolates to reduce the sequencing cost. Next-generation sequencing (NGS) was conducted for each group of mixed samples, and the proposed data analysis pipeline was used to identify viral pathogens in these mixed samples. Polymerase chain reaction (PCR) or enzyme-linked immunosorbent assay (ELISA) was individually conducted for each of these 42 isolates depending on the predicted viral types in each group. Two isolates remained unknown after these tests. Moreover, iteration mapping was implemented for each of these 2 isolates, and predicted human parechovirus (HPeV) in both. In summary, our NGS pipeline detected the following viruses among the 42 isolates: 29 human rhinoviruses (HRVs), 10 HPeVs, 1 human adenovirus (HAdV), 1 echovirus and 1 rotavirus. We then focused on the 10 identified Taiwanese HPeVs because of their reported clinical significance over HRVs. Their genomes were assembled and their genetic diversity was explored. One novel 6-bp deletion was found in one HPeV-1 virus. In terms of nucleotide heterogeneity, 64 genetic variants were detected from these HPeVs using the mapped NGS reads. Most importantly, a recombination event was found between our HPeV-3 and a known HPeV-4 strain in the database. Similar event was detected in the other HPeV-3 strains in the same clade of the phylogenetic tree. These findings demonstrated that the proposed NGS data analysis pipeline identified unknown viruses from the mixed clinical samples, revealed their genetic identity and variants, and characterized their genetic features in terms of viral evolution.",2016 Mar 17,"['Gong, Yu-Nong', 'Chen, Guang-Wu', 'Yang, Shu-Li', 'Lee, Ching-Ju', 'Shih, Shin-Ru', 'Tsao, Kuo-Chien']",PLoS One,,,True
2274f85a6caf5b13844080f9ec45cc7d01f8f952,PMC,A Next-Generation Sequencing Data Analysis Pipeline for Detecting Unknown Pathogens from Mixed Clinical Samples and Revealing Their Genetic Diversity,http://dx.doi.org/10.1371/journal.pone.0151495,PMC4795770,26986479,CC BY,"Forty-two cytopathic effect (CPE)-positive isolates were collected from 2008 to 2012. All isolates could not be identified for known viral pathogens by routine diagnostic assays. They were pooled into 8 groups of 5–6 isolates to reduce the sequencing cost. Next-generation sequencing (NGS) was conducted for each group of mixed samples, and the proposed data analysis pipeline was used to identify viral pathogens in these mixed samples. Polymerase chain reaction (PCR) or enzyme-linked immunosorbent assay (ELISA) was individually conducted for each of these 42 isolates depending on the predicted viral types in each group. Two isolates remained unknown after these tests. Moreover, iteration mapping was implemented for each of these 2 isolates, and predicted human parechovirus (HPeV) in both. In summary, our NGS pipeline detected the following viruses among the 42 isolates: 29 human rhinoviruses (HRVs), 10 HPeVs, 1 human adenovirus (HAdV), 1 echovirus and 1 rotavirus. We then focused on the 10 identified Taiwanese HPeVs because of their reported clinical significance over HRVs. Their genomes were assembled and their genetic diversity was explored. One novel 6-bp deletion was found in one HPeV-1 virus. In terms of nucleotide heterogeneity, 64 genetic variants were detected from these HPeVs using the mapped NGS reads. Most importantly, a recombination event was found between our HPeV-3 and a known HPeV-4 strain in the database. Similar event was detected in the other HPeV-3 strains in the same clade of the phylogenetic tree. These findings demonstrated that the proposed NGS data analysis pipeline identified unknown viruses from the mixed clinical samples, revealed their genetic identity and variants, and characterized their genetic features in terms of viral evolution.",2016 Mar 17,"['Gong, Yu-Nong', 'Chen, Guang-Wu', 'Yang, Shu-Li', 'Lee, Ching-Ju', 'Shih, Shin-Ru', 'Tsao, Kuo-Chien']",PLoS One,,,False
6bffaf7e11f81818a630ae32f752c963664bdc71,PMC,A Modified Coupled Spectrophotometric Method to Detect 2-5 Oligoadenylate Synthetase Activity in Prostate Cell Lines,http://dx.doi.org/10.1186/s12575-016-0038-x,PMC4797170,26997919,CC BY,"BACKGROUND: 2’-5’ oligoadenylate synthetases (OAS) are interferon inducible enzymes that polymerizes ATP to 2’-5’-linked oligomers of adenylate (2-5As). As part of the innate immune response, these enzymes are activated by viral double stranded RNA or mRNAs with significant double stranded structure. The 2-5As in turn activate RNaseL that degrade single stranded RNAs. Three distinct forms of OAS exist in human cells (OAS1, 2 and 3) with each form having multiple spliced variants. The OAS enzymes and their spliced variants have different enzyme activities. OAS enzymes also play a significant role in regulating multiple cellular processes such as proliferation and apoptosis. Moreover, Single nucleotide polymorphisms that alter OAS activity are also associated with viral infection, diabetes and cancer. Thus detection of OAS enzyme activity with a simple spectrophotometric method in cells will be important in clinical research. RESULTS: Here we propose a modified coupled spectrophotometric assay to detect 2-5 oligoadenylate synthetase (OAS) enzyme activity in prostate cell lines as a model system. The OAS enzyme from prostate cancer cell lysates was purified using Polyinosinic: polycytidylic acid (poly I:C) bound activated sepharose beads. The activated OAS enzyme eluted from Sepharose beads showed expression of p46 isoform of OAS1, generally considered the most abundant OAS isoform in elutes from DU14 cell line but not in other prostate cell line. In this assay the phosphates generated by the OAS enzymatic reaction is coupled with conversion of the substrate 2-amino-6-mercapto-7-methylpurine ribonucleoside (methylthioguanosine, a guanosine analogue; MESG) to a purine base product, 2-amino-6-mercapto-7-methylpurine and ribose1-phosphate via a catalyst purine nucleoside phosphorylase (phosphorylase) using a commercially available pyrophosphate kit. The absorbance of the purine base product is measured at 360 nm. The higher levels of phosphates detected in DU145 cell line indicates more activity of OAS in this prostate cancer cell line. CONCLUSION: The modified simple method detected OAS enzyme activity with sensitivity and specificity, which could help in detection of OAS enzymes avoiding the laborious and radioactive methods.",2016 Mar 17,"['Bhosle, Sushma M.', 'Hunt, Aisha', 'Chaudhary, Jaideep']",Biol Proced Online,,,True
09f23fe560ba923e5960707d0b4451df85253b36,PMC,Comparative analysis of routes of immunization of a live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in a heterologous virus challenge study,http://dx.doi.org/10.1186/s13567-016-0331-3,PMC4797253,26988085,CC BY,"Porcine reproductive and respiratory syndrome (PRRS) is caused by PRRS virus (PRRSV), which infects primarily the respiratory tract of pigs. Thus intranasal (IN) delivery of a potent vaccine-adjuvant formulation is promising. In this study, PRRS-MLV (VR2332) was coadministered ± an adjuvant Mycobacterium vaccae whole cell lysate or CpG ODN through intramuscular (IM) or IN route as a mist, and challenged with a heterologous PRRSV 1-4-4 IN at 42 days post-vaccination (dpv). At 14 and 26 dpv, vaccine viral RNA copies were one log greater in the plasma of PRRS-MLV IM compared to IN vaccinated pigs, and the infectious replicating vaccine virus was detected only in the IM group. In PRRS-MLV ± adjuvant IM vaccinated pigs, reduced viral RNA load and absence of the replicating challenged virus was observed at 7, 10 and 14 days post-challenge (dpc). At 14 dpc, in BAL fluid ≥5 log viral RNA copies were detected in all the pig groups, but the replicating challenged virus was undetectable only in IM groups. Immunologically, virus neutralizing antibody titers in the plasma of IM (but not IN) vaccine groups was ≥8 against the vaccine and challenged viruses. At 26 dpv, PRRS-MLV IM (without adjuvant) received pigs had significantly increased population of CD4 and CD8 T cells in PBMC. At 14 dpc, relatively increased population of IFN-γ(+) total lymphocytes, NK, CD4, CD8 and γδ T cells were observed in the MLV-IM group. In conclusion, PRRS-MLV IM vaccination induced the virus specific T cell response in pigs, but still it is required to improve its cross-protective efficacy.",2016 Mar 17,"['Ouyang, Kang', 'Hiremath, Jagadish', 'Binjawadagi, Basavaraj', 'Shyu, Duan-Liang', 'Dhakal, Santosh', 'Arcos, Jesus', 'Schleappi, Rose', 'Holman, Lynette', 'Roof, Michael', 'Torrelles, Jordi B.', 'Renukaradhya, Gourapura J.']",Vet Res,,,True
63db9e65e1430b32da0f2f3d88fd45ce88eaab31,PMC,Training on the care of patients with respiratory syndrome of middle east-coronavirus and ebola virus based on clinical simulation,http://dx.doi.org/10.1186/2197-425X-3-S1-A732,PMC4798186,,CC BY,,2015 Oct 1,"['Palamidessi Domínguez, J', 'Valdivia de la Fuente, M', 'Rubio Muñoz, JJ', 'Alcántara Carmona, S', 'Palacios Castañeda, D', 'Martínez Sanz, N', 'Lobo Valbuena, B', 'Fernández Rivas, R', 'Pérez Lucendo, A', 'Pérez Pérez, L']",Intensive Care Med Exp,,,False
bfdf1cc025285b3c20fdde66f5de3be60b46930e,PMC,Locally Produced IL-10 Limits Cutaneous Vaccinia Virus Spread,http://dx.doi.org/10.1371/journal.ppat.1005493,PMC4798720,26991092,CC0,"Skin infection with the poxvirus vaccinia (VV) elicits a powerful, inflammatory cellular response that clears virus infection in a coordinated, spatially organized manner. Given the high concentration of pro-inflammatory effectors at areas of viral infection, it is unclear how tissue pathology is limited while virus-infected cells are being eliminated. To better understand the spatial dynamics of the anti-inflammatory response to a cutaneous viral infection, we first screened cytokine mRNA expression levels after epicutaneous (ec.) VV infection and found a large increase the anti-inflammatory cytokine IL-10. Ex vivo analyses revealed that T cells in the skin were the primary IL-10-producing cells. To understand the distribution of IL-10-producing T cells in vivo, we performed multiphoton intravital microscopy (MPM) of VV-infected mice, assessing the location and dynamic behavior of IL-10 producing cells. Although virus-specific T cells were distributed throughout areas of the inflamed skin lacking overt virus-infection, IL-10(+) cells closely associated with large keratinocytic foci of virus replication where they exhibited similar motility patterns to bulk antigen-specific CD8(+) T cells. Paradoxically, neutralizing secreted IL-10 in vivo with an anti-IL-10 antibody increased viral lesion size and viral replication. Additional analyses demonstrated that IL-10 antibody administration decreased recruitment of CCR2(+) inflammatory monocytes, which were important for reducing viral burden in the infected skin. Based upon these findings, we conclude that spatially concentrated IL-10 production limits cutaneous viral replication and dissemination, likely through modulation of the innate immune repertoire at the site of viral growth.",2016 Mar 18,"['Cush, Stephanie S.', 'Reynoso, Glennys V.', 'Kamenyeva, Olena', 'Bennink, Jack R.', 'Yewdell, Jonathan W.', 'Hickman, Heather D.']",PLoS Pathog,,,True
db7ddc7b6e1689aed55b17716e2c2d3309b56f90,PMC,The role of respiratory viruses in the etiology of bacterial pneumonia: An ecological perspective,http://dx.doi.org/10.1093/emph/eow007,PMC4801059,26884414,CC BY,"Pneumonia is the leading cause of death among children less than 5 years old worldwide. A wide range of viral, bacterial and fungal agents can cause pneumonia: although viruses are the most common etiologic agent, the severity of clinical symptoms associated with bacterial pneumonia and increasing antibiotic resistance makes bacterial pneumonia a major public health concern. Bacterial pneumonia can follow upper respiratory viral infection and complicate lower respiratory viral infection. Secondary bacterial pneumonia is a major cause of influenza-related deaths. In this review, we evaluate the following hypotheses: (i) respiratory viruses influence the etiology of pneumonia by altering bacterial community structure in the upper respiratory tract (URT) and (ii) respiratory viruses promote or inhibit colonization of the lower respiratory tract (LRT) by certain bacterial species residing in the URT. We conducted a systematic review of the literature to examine temporal associations between respiratory viruses and bacteria and a targeted review to identify potential mechanisms of interactions. We conclude that viruses both alter the bacterial community in the URT and promote bacterial colonization of the LRT. However, it is uncertain whether changes in the URT bacterial community play a substantial role in pneumonia etiology. The exception is Streptococcus pneumoniae where a strong link between viral co-infection, increased carriage and pneumococcal pneumonia has been established.",2016 Feb 15,"['Lee, Kyu Han', 'Gordon, Aubree', 'Foxman, Betsy']",Evol Med Public Health,,,True
7dc5c4c3a782bb77aaa9f3e03f16f7fa703cfd54,PMC,Evaluation of recombinase polymerase amplification for detection of begomoviruses by plant diagnostic clinics,http://dx.doi.org/10.1186/s12985-016-0504-8,PMC4802622,27000806,CC BY,"BACKGROUND: Plant viruses in the genus Begomovirus, family Geminiviridae often cause substantial crop losses. These viruses have been emerging in many locations throughout the tropics and subtropics. Like many plant viruses, they are often not recognized by plant diagnostic clinics due in large part to the lack of rapid and cost effective assays. An isothermal amplification assay, Recombinase polymerase amplification (RPA), was evaluated for its ability to detect three begomoviruses and for its suitability for use in plant diagnostic clinics. Methods for DNA extraction and separation of amplicons from proteins used in the assay were modified and compared to RPA manufacturer’s protocols. The modified RPA assays were compared to PCR assays for sensitivity, use in downstream applications, cost, and speed. RESULTS: Recombinase polymerase amplification (RPA) assays for the detection of Bean golden yellow mosaic virus, Tomato mottle virus and Tomato yellow leaf curl virus (TYLCV) were specific, only amplifying the target viruses in three different host species. RPA was able to detect the target virus when the template was in a crude extract generated using a simple inexpensive extraction method, while PCR was not. Separation of RPA-generated amplicons from DNA-binding proteins could be accomplished by several methods, all of which were faster and less expensive than that recommended by the manufacturer. Use of these modifications resulted in an RPA assay that was faster than PCR but with a similar reagent cost. This modified RPA was the more cost effective assay when labor is added to the cost since RPA can be performed much faster than PCR. RPA had a sensitivity approximate to that of ELISA when crude extract was used as template. RPA-generated amplicons could be used in downstream applications (TA cloning, digestion with a restriction endonuclease, direct sequencing) similar to PCR but unlike some other isothermal reactions. CONCLUSIONS: RPA could prove useful for the cost effective detection of plant viruses by plant diagnostic clinics. It can be performed in one hour or less with a reagent cost similar to that of PCR but with a lower labor cost, and with an acceptable level of sensitivity and specificity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0504-8) contains supplementary material, which is available to authorized users.",2016 Mar 22,"['Londoño, Maria A.', 'Harmon, Carrie L.', 'Polston, Jane E.']",Virol J,,,False
2e5b75124a437e9592822b4ece85c99f34021fc5,PMC,Evaluation of recombinase polymerase amplification for detection of begomoviruses by plant diagnostic clinics,http://dx.doi.org/10.1186/s12985-016-0504-8,PMC4802622,27000806,CC BY,"BACKGROUND: Plant viruses in the genus Begomovirus, family Geminiviridae often cause substantial crop losses. These viruses have been emerging in many locations throughout the tropics and subtropics. Like many plant viruses, they are often not recognized by plant diagnostic clinics due in large part to the lack of rapid and cost effective assays. An isothermal amplification assay, Recombinase polymerase amplification (RPA), was evaluated for its ability to detect three begomoviruses and for its suitability for use in plant diagnostic clinics. Methods for DNA extraction and separation of amplicons from proteins used in the assay were modified and compared to RPA manufacturer’s protocols. The modified RPA assays were compared to PCR assays for sensitivity, use in downstream applications, cost, and speed. RESULTS: Recombinase polymerase amplification (RPA) assays for the detection of Bean golden yellow mosaic virus, Tomato mottle virus and Tomato yellow leaf curl virus (TYLCV) were specific, only amplifying the target viruses in three different host species. RPA was able to detect the target virus when the template was in a crude extract generated using a simple inexpensive extraction method, while PCR was not. Separation of RPA-generated amplicons from DNA-binding proteins could be accomplished by several methods, all of which were faster and less expensive than that recommended by the manufacturer. Use of these modifications resulted in an RPA assay that was faster than PCR but with a similar reagent cost. This modified RPA was the more cost effective assay when labor is added to the cost since RPA can be performed much faster than PCR. RPA had a sensitivity approximate to that of ELISA when crude extract was used as template. RPA-generated amplicons could be used in downstream applications (TA cloning, digestion with a restriction endonuclease, direct sequencing) similar to PCR but unlike some other isothermal reactions. CONCLUSIONS: RPA could prove useful for the cost effective detection of plant viruses by plant diagnostic clinics. It can be performed in one hour or less with a reagent cost similar to that of PCR but with a lower labor cost, and with an acceptable level of sensitivity and specificity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0504-8) contains supplementary material, which is available to authorized users.",2016 Mar 22,"['Londoño, Maria A.', 'Harmon, Carrie L.', 'Polston, Jane E.']",Virol J,,,False
3e3dc81c5985a37a950e4f63ffa10f4d5f9581aa,PMC,Evaluation of recombinase polymerase amplification for detection of begomoviruses by plant diagnostic clinics,http://dx.doi.org/10.1186/s12985-016-0504-8,PMC4802622,27000806,CC BY,"BACKGROUND: Plant viruses in the genus Begomovirus, family Geminiviridae often cause substantial crop losses. These viruses have been emerging in many locations throughout the tropics and subtropics. Like many plant viruses, they are often not recognized by plant diagnostic clinics due in large part to the lack of rapid and cost effective assays. An isothermal amplification assay, Recombinase polymerase amplification (RPA), was evaluated for its ability to detect three begomoviruses and for its suitability for use in plant diagnostic clinics. Methods for DNA extraction and separation of amplicons from proteins used in the assay were modified and compared to RPA manufacturer’s protocols. The modified RPA assays were compared to PCR assays for sensitivity, use in downstream applications, cost, and speed. RESULTS: Recombinase polymerase amplification (RPA) assays for the detection of Bean golden yellow mosaic virus, Tomato mottle virus and Tomato yellow leaf curl virus (TYLCV) were specific, only amplifying the target viruses in three different host species. RPA was able to detect the target virus when the template was in a crude extract generated using a simple inexpensive extraction method, while PCR was not. Separation of RPA-generated amplicons from DNA-binding proteins could be accomplished by several methods, all of which were faster and less expensive than that recommended by the manufacturer. Use of these modifications resulted in an RPA assay that was faster than PCR but with a similar reagent cost. This modified RPA was the more cost effective assay when labor is added to the cost since RPA can be performed much faster than PCR. RPA had a sensitivity approximate to that of ELISA when crude extract was used as template. RPA-generated amplicons could be used in downstream applications (TA cloning, digestion with a restriction endonuclease, direct sequencing) similar to PCR but unlike some other isothermal reactions. CONCLUSIONS: RPA could prove useful for the cost effective detection of plant viruses by plant diagnostic clinics. It can be performed in one hour or less with a reagent cost similar to that of PCR but with a lower labor cost, and with an acceptable level of sensitivity and specificity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0504-8) contains supplementary material, which is available to authorized users.",2016 Mar 22,"['Londoño, Maria A.', 'Harmon, Carrie L.', 'Polston, Jane E.']",Virol J,,,True
3e6c85e4e3409c135ec4d5525290a9908aac2b58,PMC,Actin- and clathrin-dependent mechanisms regulate interferon gamma release after stimulation of human immune cells with respiratory syncytial virus,http://dx.doi.org/10.1186/s12985-016-0506-6,PMC4802911,27004689,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) can cause recurrent and severe respiratory tract infections. Cytoskeletal proteins are often involved during viral infections, either for cell entry or the initiation of the immune response. The importance of actin and clathrin dynamics for cell entry and the initiation of the cellular immune response against RSV in human immune cells is not known yet. The aim of this study was to investigate the role of actin and clathrin on cell entry of RSV and the subsequent effect on T cell activation and interferon gamma release in human immune cells. METHODS: Peripheral blood mononuclear cells and purified monocytes were isolated from healthy adults and stimulated in vitro with RSV. Actin and clathrin dynamics were inhibited with respectively cytochalasin D and chlorpromazine. T cell receptor signaling was inhibited with cyclosporin A. Flow cytometry was used to determine the role of actin and clathrin on cell entry and T cell activation by RSV. Enzyme-linked immunosorbent assays were used to investigate the contribution of actin and clathrin on the release of interferon gamma. RESULTS: Cell entry, virus gene transcription and interferon gamma release are actin-dependent. Post-endocytic processes like the increased expression of major histocompatibility complex II on monocytes , T cell activation and the release of interferon gamma are clathrin-dependent. Finally, T cell receptor signaling affects T cell activation, whereas soluble interleukin 18 is dispensable. CONCLUSION: Analysis of cell entry and interferon gamma release after infection with RSV reveals the importance of actin- and clathrin-dependent signaling in human immune cells. Insights into the cellular biology of the human immune response against respiratory syncytial virus will provide a better understanding of disease pathogenesis and may prove useful in the development of preventive strategies.",2016 Mar 22,"['Jans, Jop', 'elMoussaoui, Hicham', 'de Groot, Ronald', 'de Jonge, Marien I.', 'Ferwerda, Gerben']",Virol J,,,True
90d553a545579b2e27d0899c558e004ff33cd0f4,PMC,Infection with and Carriage of Mycoplasma pneumoniae in Children,http://dx.doi.org/10.3389/fmicb.2016.00329,PMC4803743,27047456,CC BY,"“Atypical” pneumonia was described as a distinct and mild form of community-acquired pneumonia (CAP) already before Mycoplasma pneumoniae had been discovered and recognized as its cause. M. pneumoniae is detected in CAP patients most frequently among school-aged children from 5 to 15 years of age, with a decline after adolescence and tapering off in adulthood. Detection rates by polymerase chain reaction (PCR) or serology in children with CAP admitted to the hospital amount 4–39%. Although the infection is generally mild and self-limiting, patients of every age can develop severe or extrapulmonary disease. Recent studies indicate that high rates of healthy children carry M. pneumoniae in the upper respiratory tract and that current diagnostic PCR or serology cannot discriminate between M. pneumoniae infection and carriage. Further, symptoms and radiologic features are not specific for M. pneumoniae infection. Thus, patients may be unnecessarily treated with antimicrobials against M. pneumoniae. Macrolides are the first-line antibiotics for this entity in children younger than 8 years of age. Overall macrolides are extensively used worldwide, and this has led to the emergence of macrolide-resistant M. pneumoniae, which may be associated with severe clinical features and more extrapulmonary complications. This review focuses on the characteristics of M. pneumoniae infections in children, and exemplifies that simple clinical decision rules may help identifying children at high risk for CAP due to M. pneumoniae. This may aid physicians in prescribing appropriate first-line antibiotics, since current diagnostic tests for M. pneumoniae infection are not reliably predictive.",2016 Mar 23,"['Meyer Sauteur, Patrick M.', 'Unger, Wendy W. J.', 'Nadal, David', 'Berger, Christoph', 'Vink, Cornelis', 'van Rossum, Annemarie M. C.']",Front Microbiol,,,True
b562f1a519bc6a12df5e62930bdf4345cf0f7ce9,PMC,Utilization of the Emergency Department and Predicting Factors Associated With Its Use at the Saudi Ministry of Health General Hospitals,http://dx.doi.org/10.5539/gjhs.v8n1p90,PMC4803979,26234993,CC BY,"Overuse of emergency rooms (ER) is a public health problem. To investigate this issue, a cross-sectional survey was conducted at the ERs of King Abdul-Aziz Hospital, King Fahd Hospital, and Al-Thaghor Hospital in November 2013 with the aims of estimating emergency service utilization for non-urgent cases, identifying the predictors of ER utilization for non-urgent cases, and measuring patients’ knowledge of primary healthcare centers (PHCCs). Patients were interviewed using a structured questionnaire and the data were analyzed using the Statistical Package for the Social Sciences. We recruited 300 patients; males comprised 50.7% of the sample. A higher proportion of patients with non-urgent cases visited the ER three to four times a year (P=0.001). A higher proportion of patients without emergencies had not attempted to visit an outpatient clinic before the ER (P=0.003). Most patients without emergencies thought the ER was the first place to consult in case of illness. Most patients who visited the ER were single, < 15 years, and had lower incomes. Patients requested ER services for primary care-treatable conditions because of limited services and resources as well as limited working hours at PHCCs. Most patients (90.0%) were knowledgeable about PHCCs, with those of lower education being more knowledgeable. Patients reported long ER waiting times (≥ 3 hours), no organization (85.9%), and lack of medical staff. Overall, overuse of ER services is high at the Ministry of Health hospitals in Jeddah. The risk factors for ER overuse are age < 15 years, singlehood, and low incomes. Policy makers and health providers have a challenging task to control ER overuse. We recommend developing strategies to implement policies aimed at reducing non-urgent ER use as well as making healthcare services more available to the population.",2016 Jan 15,"['Dawoud, Sundus O.', 'Ahmad, Alaeddin Mohammad K.', 'Alsharqi, Omar Z.', 'Al-Raddadi, Rajaa M.']",Glob J Health Sci,,,True
925d90afe2cf113f16a0e28943763916963fdf24,PMC,Interpreting whole genome sequencing for investigating tuberculosis transmission: a systematic review,http://dx.doi.org/10.1186/s12916-016-0566-x,PMC4804562,27005433,CC BY,"BACKGROUND: Whole genome sequencing (WGS) is becoming an important part of epidemiological investigations of infectious diseases due to greater resolution and cost reductions compared to traditional typing approaches. Many public health and clinical teams will increasingly use WGS to investigate clusters of potential pathogen transmission, making it crucial to understand the benefits and assumptions of the analytical methods for investigating the data. We aimed to understand how different approaches affect inferences of transmission dynamics and outline limitations of the methods. METHODS: We comprehensively searched electronic databases for studies that presented methods used to interpret WGS data for investigating tuberculosis (TB) transmission. Two authors independently selected studies for inclusion and extracted data. Due to considerable methodological heterogeneity between studies, we present summary data with accompanying narrative synthesis rather than pooled analyses. RESULTS: Twenty-five studies met our inclusion criteria. Despite the range of interpretation tools, the usefulness of WGS data in understanding TB transmission often depends on the amount of genetic diversity in the setting. Where diversity is small, distinguishing re-infections from relapses may be impossible; interpretation may be aided by the use of epidemiological data, examining minor variants and deep sequencing. Conversely, when within-host diversity is large, due to genetic hitchhiking or co-infection of two dissimilar strains, it is critical to understand how it arose. Greater understanding of microevolution and mixed infection will enhance interpretation of WGS data. CONCLUSIONS: As sequencing studies have sampled more intensely and integrated multiple sources of information, the understanding of TB transmission and diversity has grown, but there is still much to be learnt about the origins of diversity that will affect inferences from these data. Public health teams and researchers should combine epidemiological, clinical and WGS data to strengthen investigations of transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-016-0566-x) contains supplementary material, which is available to authorized users.",2016 Mar 23,"['Hatherell, Hollie-Ann', 'Colijn, Caroline', 'Stagg, Helen R.', 'Jackson, Charlotte', 'Winter, Joanne R.', 'Abubakar, Ibrahim']",BMC Med,,,True
8dc3e3104105b1c360fdfe01de88e4f35d6977d0,PMC,A Highly Efficient and Simple Construction Strategy for Producing Recombinant Baculovirus Bombyx mori Nucleopolyhedrovirus,http://dx.doi.org/10.1371/journal.pone.0152140,PMC4805210,27008267,CC BY,"The silkworm baculovirus expression system is widely used to produce recombinant proteins. Several strategies for constructing recombinant viruses that contain foreign genes have been reported. Here, we developed a novel defective-rescue BmNPV Bacmid (reBmBac) expression system. A CopyControl origin of replication was introduced into the viral genome to facilitate its genetic manipulation in Escherichia coli and to ensure the preparation of large amounts of high quality reBmBac DNA as well as high quality recombinant baculoviruses. The ORF1629, cathepsin and chitinase genes were partially deleted or rendered defective to improve the efficiency of recombinant baculovirus generation and the expression of foreign genes. The system was validated by the successful expression of luciferase reporter gene and porcine interferon γ. This system can be used to produce batches of recombinant baculoviruses and target proteins rapidly and efficiently in silkworms.",2016 Mar 23,"['Liu, Xingjian', 'Wei, Yonglong', 'Li, Yinü', 'Li, Haoyang', 'Yang, Xin', 'Yi, Yongzhu', 'Zhang, Zhifang']",PLoS One,,,True
18073920e12ee20d939dee5116c586da8accfd82,PMC,A Novel Sample Processing Method for Rapid Detection of Tuberculosis in the Stool of Pediatric Patients Using the Xpert MTB/RIF Assay,http://dx.doi.org/10.1371/journal.pone.0151980,PMC4805262,27007974,CC BY,"BACKGROUND: Tuberculosis (TB) is difficult to diagnose in children using molecular tests, because children have difficulty providing respiratory samples. Stool could replace sputum for diagnostic TB testing if adequate sample processing techniques were available. METHODS: We developed a rapid method to process large volumes of stool for downstream testing by the Xpert MTB/RIF (Xpert) TB-detection assay. The method was tested and optimized on stool samples spiked with known numbers of M. tuberculosis colony forming units (CFU), and stools from M. tuberculosis-infected cynomolgus macaques (Macaca fascicularis). Performance was scored on number of positive Xpert tests, the cycle thresholds (Cts) of the Xpert sample-processing control (SPC), and the Cts of the M. tuberculosis-specific rpoB probes. The method was then validated on 20 confirmed TB cases and 20 controls in Durban, South Africa. RESULTS: The assay’s analytical limit of detection was 1,000 CFU/g of stool. As much as one gram of spiked stool could be tested without showing increased PCR inhibition. In analytical spiking experiments using human stool, 1g samples provided the best sensitivity compared to smaller amounts of sample. However, in Macaques with TB, 0.6g stool samples performed better than either 0.2g or 1.2g samples. Testing the stool of pediatric TB suspects and controls suggested an assay sensitivity of 85% (95% CI 0.6–0.9) and 84% (95% CI 0.6–0.96) for 0.6g and 1.2g stool samples, respectively, and a specificity of 100% (95% CI 0.77–1) and 94% (95% CI 0.7–0.99), respectively. CONCLUSION: This novel approach may permit simple and rapid detection of TB using pediatric stool samples.",2016 Mar 23,"['Banada, Padmapriya P.', 'Naidoo, Uvistra', 'Deshpande, Srinidhi', 'Karim, Farina', 'Flynn, JoAnne L.', 'O’Malley, Melanie', 'Jones, Martin', 'Nanassy, Oliver', 'Jeena, Prakash', 'Alland, David']",PLoS One,,,True
8e549a3356d7bd16111c4f682ae12a21ad4c5633,PMC,Wildlife Trade and Human Health in Lao PDR: An Assessment of the Zoonotic Disease Risk in Markets,http://dx.doi.org/10.1371/journal.pone.0150666,PMC4805265,27008628,CC BY,"Although the majority of emerging infectious diseases can be linked to wildlife sources, most pathogen spillover events to people could likely be avoided if transmission was better understood and practices adjusted to mitigate risk. Wildlife trade can facilitate zoonotic disease transmission and represents a threat to human health and economies in Asia, highlighted by the 2003 SARS coronavirus outbreak, where a Chinese wildlife market facilitated pathogen transmission. Additionally, wildlife trade poses a serious threat to biodiversity. Therefore, the combined impacts of Asian wildlife trade, sometimes termed bush meat trade, on public health and biodiversity need assessing. From 2010 to 2013, observational data were collected in Lao PDR from markets selling wildlife, including information on volume, form, species and price of wildlife; market biosafety and visitor origin. The potential for traded wildlife to host zoonotic diseases that pose a serious threat to human health was then evaluated at seven markets identified as having high volumes of trade. At the seven markets, during 21 observational surveys, 1,937 alive or fresh dead mammals (approximately 1,009 kg) were observed for sale, including mammals from 12 taxonomic families previously documented to be capable of hosting 36 zoonotic pathogens. In these seven markets, the combination of high wildlife volumes, high risk taxa for zoonoses and poor biosafety increases the potential for pathogen presence and transmission. To examine the potential conservation impact of trade in markets, we assessed the status of 33,752 animals observed during 375 visits to 93 markets, under the Lao PDR Wildlife and Aquatic Law. We observed 6,452 animals listed by Lao PDR as near extinct or threatened with extinction. The combined risks of wildlife trade in Lao PDR to human health and biodiversity highlight the need for a multi-sector approach to effectively protect public health, economic interests and biodiversity.",2016 Mar 23,"['Greatorex, Zoe F.', 'Olson, Sarah H.', 'Singhalath, Sinpakone', 'Silithammavong, Soubanh', 'Khammavong, Kongsy', 'Fine, Amanda E.', 'Weisman, Wendy', 'Douangngeun, Bounlom', 'Theppangna, Watthana', 'Keatts, Lucy', 'Gilbert, Martin', 'Karesh, William B.', 'Hansel, Troy', 'Zimicki, Susan', 'O’Rourke, Kathleen', 'Joly, Damien O.', 'Mazet, Jonna A. K.']",PLoS One,,,True
ce75acf2c22c37fdd88ecf5ed40c6713443fef47,PMC,"Cross-Reactivity of TCR Repertoire: Current Concepts, Challenges, and Implication for Allotransplantation",http://dx.doi.org/10.3389/fimmu.2016.00089,PMC4805583,27047489,CC BY,"Being able to track donor reactive T cells during the course of organ transplantation is a key to improve the graft survival, to prevent graft dysfunction, and to adapt the immunosuppressive regimen. The attempts of transplant immunologists have been for long hampered by the large size of the alloreactive T cell repertoire. Understanding how self-TCR can interact with allogeneic MHC is a key to critically appraise the different assays available to analyze the TCR Vβ repertoire usage. In this report, we will review conceptually and experimentally the process of cross-reactivity. We will then highlight what can be learned from allotransplantation, a situation of artificial cross-reactivity. Finally, the low- and high-resolution techniques to characterize the TCR Vβ repertoire usage in transplantation will be critically discussed.",2016 Mar 24,"['Degauque, Nicolas', 'Brouard, Sophie', 'Soulillou, Jean-Paul']",Front Immunol,,,True
d65ee92563369f173d038fe15c6f066c4f134385,PMC,The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles,http://dx.doi.org/10.1371/journal.ppat.1005501,PMC4806877,27010636,CC BY,"Arenaviruses cause severe diseases in humans but establish asymptomatic, lifelong infections in rodent reservoirs. Persistently-infected rodents harbor high levels of defective interfering (DI) particles, which are thought to be important for establishing persistence and mitigating virus-induced cytopathic effect. Little is known about what drives the production of DI particles. We show that neither the PPXY late domain encoded within the lymphocytic choriomeningitis virus (LCMV) matrix protein nor a functional endosomal sorting complex transport (ESCRT) pathway is absolutely required for the generation of standard infectious virus particles. In contrast, DI particle release critically requires the PPXY late domain and is ESCRT-dependent. Additionally, the terminal tyrosine in the PPXY motif is reversibly phosphorylated and our findings indicate that this posttranslational modification may regulate DI particle formation. Thus we have uncovered a new role for the PPXY late domain and a possible mechanism for its regulation.",2016 Mar 24,"['Ziegler, Christopher M.', 'Eisenhauer, Philip', 'Bruce, Emily A.', 'Weir, Marion E.', 'King, Benjamin R.', 'Klaus, Joseph P.', 'Krementsov, Dimitry N.', 'Shirley, David J.', 'Ballif, Bryan A.', 'Botten, Jason']",PLoS Pathog,,,True
991aed7275084ce0661be421e281a8f47dcc8637,PMC,Selective Preference of Parallel DNA Triplexes Is Due to the Disruption of Hoogsteen Hydrogen Bonds Caused by the Severe Nonisostericity between the G*GC and T*AT Triplets,http://dx.doi.org/10.1371/journal.pone.0152102,PMC4807104,27010368,CC BY,"Implications of DNA, RNA and RNA.DNA hybrid triplexes in diverse biological functions, diseases and therapeutic applications call for a thorough understanding of their structure-function relationships. Despite exhaustive studies mechanistic rationale for the discriminatory preference of parallel DNA triplexes with G(*)GC & T(*)AT triplets still remains elusive. Here, we show that the highest nonisostericity between the G(*)GC & T(*)AT triplets imposes extensive stereochemical rearrangements contributing to context dependent triplex destabilisation through selective disruption of Hoogsteen scheme of hydrogen bonds. MD simulations of nineteen DNA triplexes with an assortment of sequence milieu reveal for the first time fresh insights into the nature and extent of destabilization from a single (non-overlapping), double (overlapping) and multiple pairs of nonisosteric base triplets (NIBTs). It is found that a solitary pair of NIBTs, feasible either at a G(*)GC/T(*)AT or T(*)AT/G(*)GC triplex junction, does not impinge significantly on triplex stability. But two overlapping pairs of NIBTs resulting from either a T(*)AT or a G(*)GC interruption disrupt Hoogsteen pair to a noncanonical mismatch destabilizing the triplex by ~10 to 14 kcal/mol, implying that their frequent incidence in multiples, especially, in short sequences could even hinder triplex formation. The results provide (i) an unambiguous and generalised mechanistic rationale for the discriminatory trait of parallel triplexes, including those studied experimentally (ii) clarity for the prevalence of antiparallel triplexes and (iii) comprehensive perspectives on the sequence dependent influence of nonisosteric base triplets useful in the rational design of TFO’s against potential triplex target sites.",2016 Mar 24,"['Goldsmith, Gunaseelan', 'Rathinavelan, Thenmalarchelvi', 'Yathindra, Narayanarao']",PLoS One,,,True
d3d29e7ae22aaff4cdc9769cbe97e57c438d5ef2,PMC,Chasing Ebola through the Endosomal Labyrinth,http://dx.doi.org/10.1128/mBio.00346-16,PMC4807365,27006455,CC BY,"During virus entry, the surface glycoprotein of Ebola virus (EBOV) undergoes a complex set of transformations within the endosomal network. Tools to study EBOV entry have been limited to static immunofluorescence or biochemical and functional analysis. In a recent article in mBio, Spence et al. reported a novel, live-cell-imaging method that tracks this transformational journey of EBOV in real time [J. S. Spence, T. B. Krause, E. Mittler, R. K. Jangra, and K. Chandran, mBio 7(1):e01857-15, 2016, http://dx.doi.org/10.1128/mBio.01857-15]. The assay validates known mechanisms of EBOV entry and sheds light on some novel intricacies. Direct evidence supports the hypothesis that fusion is a rare event that starts in maturing early endosomes, is completed in late endosomes, and occurs entirely in Niemann-Pick C1 (NPC1)-positive (NPC1(+)) compartments. The study demonstrated that lipid mixing and productive fusion are temporally decoupled, with different energetic barriers and a protease-dependent step between the two events. Analysis of the mechanism of action of an important class of EBOV neutralizing antibodies, such as KZ52 and ZMapp, provides direct evidence that these antibodies act by inhibiting the membrane fusion.",2016 Mar 22,"Aman, M. Javad",mBio,,,True
8e014e2133b319d93ba7e9341ffe33bab3f9e265,PMC,A HLA-A2-restricted CTL epitope induces anti-tumor effects against human lung cancer in mouse xenograft model,,PMC4808025,26621839,CC BY,"Cancer immunotherapy is attractive for antigen-specific T cell-mediated anti-tumor therapy, especially in induction of cytotoxic T lymphocytes. In this report, we evaluated human CTL epitope-induced anti-tumor effects in human lung cancer xenograft models. The tumor associated antigen L6 (TAL6) is highly expressed in human lung cancer cell lines and tumor specimens as compared to normal lung tissues. TAL6 derived peptides strongly inhibited tumor growth, cancer metastasis and prolonged survival time in HLA-A2 transgenic mice immunized with a formulation of T-helper (Th) peptide, synthetic CpG ODN, and adjuvant Montanide ISA-51 (ISA-51). Adoptive transfer of peptide-induced CTL cells from HLA-A2 transgenic mice into human tumor xenograft SCID mice significantly inhibited tumor growth. Furthermore, combination of CTL-peptide immunotherapy and gemcitabine additively improved the therapeutic effects. This pre-clinical evaluation model provides a useful platform to develop efficient immunotherapeutic drugs to treat lung cancer and demonstrates a promising strategy with benefit of antitumor immune responses worthy of further development in clinical trials.",2015 Nov 26,"['Sher, Yuh-Pyng', 'Lin, Su-I', 'Chen, I-Hua', 'Liu, Hsin-Yu', 'Lin, Chen-Yuan', 'Chiang, I-Ping', 'Roffler, Steve', 'Chen, Hsin-Wei', 'Liu, Shih-Jen']",Oncotarget,,,True
53b682ee21a1000891bc2cc0363feea27dce7398,PMC,A HLA-A2-restricted CTL epitope induces anti-tumor effects against human lung cancer in mouse xenograft model,,PMC4808025,26621839,CC BY,"Cancer immunotherapy is attractive for antigen-specific T cell-mediated anti-tumor therapy, especially in induction of cytotoxic T lymphocytes. In this report, we evaluated human CTL epitope-induced anti-tumor effects in human lung cancer xenograft models. The tumor associated antigen L6 (TAL6) is highly expressed in human lung cancer cell lines and tumor specimens as compared to normal lung tissues. TAL6 derived peptides strongly inhibited tumor growth, cancer metastasis and prolonged survival time in HLA-A2 transgenic mice immunized with a formulation of T-helper (Th) peptide, synthetic CpG ODN, and adjuvant Montanide ISA-51 (ISA-51). Adoptive transfer of peptide-induced CTL cells from HLA-A2 transgenic mice into human tumor xenograft SCID mice significantly inhibited tumor growth. Furthermore, combination of CTL-peptide immunotherapy and gemcitabine additively improved the therapeutic effects. This pre-clinical evaluation model provides a useful platform to develop efficient immunotherapeutic drugs to treat lung cancer and demonstrates a promising strategy with benefit of antitumor immune responses worthy of further development in clinical trials.",2015 Nov 26,"['Sher, Yuh-Pyng', 'Lin, Su-I', 'Chen, I-Hua', 'Liu, Hsin-Yu', 'Lin, Chen-Yuan', 'Chiang, I-Ping', 'Roffler, Steve', 'Chen, Hsin-Wei', 'Liu, Shih-Jen']",Oncotarget,,,False
786da349a33148e24e09edd6378da80ea2f40e07,PMC,Common variations in TERT-CLPTM1L locus are reproducibly associated with the risk of nasopharyngeal carcinoma in Chinese populations,,PMC4808031,26621837,CC BY,"Associations between single nucleotide polymorphisms (SNPs) at 5p15 (TERT-CLPTM1L) and multiple cancer types have been reported. We examined whether polymorphisms in the TERT-CLPTM1L locus were related to the risk of developing nasopharyngeal carcinoma (NPC) among Chinese populations. In the first stage, 26 tag SNPs were genotyped in a Guangxi population (855 patients and 1036 controls). In the second stage, the SNPs, which showed significant association, were further genotyped in a Guangdong population (997 patients and 972 controls). Functional analyses were conducted to verify the biological relevance of the associated polymorphism. In the 1st stage, four SNPs (rs2736098, rs2735845, rs402710, and rs401681) were significantly associated with the risk of developing NPC. After the 2nd stage validation, rs2735845 and rs401681 were independently associated with the risk of developing NPC in the additive model (rs2735845, OR = 1.19, 95% CI = 1.04–1.37, P = 0.011; rs401681, OR = 0.85, 95% CI = 0.74–0.99, P = 0.034). Furthermore, we observed higher CLPTM1L messenger RNA levels in fetal mesenchymal stem cells from the rs2735845 G allele carriers compared with that from non-carriers. In addition, using an immunohistochemistry assay, we observed higher TERT and CLPTM1L levels in NPC tissues compared with that in non-cancerous nasopharyngeal tissues. Our findings suggest that polymorphisms in the TERT-CLPTM1L locus may play a role in mediating the susceptibility to NPC in Chinese populations.",2015 Nov 26,"['Zhang, Yang', 'Zhang, Xiaoai', 'Zhang, Hongxing', 'Zhai, Yun', 'Wang, Zhifu', 'Li, Peiyao', 'Yu, Lixia', 'Xia, Xia', 'Zhang, Ying', 'Zeng, Yixin', 'He, Fuchu', 'Zhou, Gangqiao']",Oncotarget,,,True
2810296105b6ae2ca21d299d27f83c6d1b071f28,PMC,Common variations in TERT-CLPTM1L locus are reproducibly associated with the risk of nasopharyngeal carcinoma in Chinese populations,,PMC4808031,26621837,CC BY,"Associations between single nucleotide polymorphisms (SNPs) at 5p15 (TERT-CLPTM1L) and multiple cancer types have been reported. We examined whether polymorphisms in the TERT-CLPTM1L locus were related to the risk of developing nasopharyngeal carcinoma (NPC) among Chinese populations. In the first stage, 26 tag SNPs were genotyped in a Guangxi population (855 patients and 1036 controls). In the second stage, the SNPs, which showed significant association, were further genotyped in a Guangdong population (997 patients and 972 controls). Functional analyses were conducted to verify the biological relevance of the associated polymorphism. In the 1st stage, four SNPs (rs2736098, rs2735845, rs402710, and rs401681) were significantly associated with the risk of developing NPC. After the 2nd stage validation, rs2735845 and rs401681 were independently associated with the risk of developing NPC in the additive model (rs2735845, OR = 1.19, 95% CI = 1.04–1.37, P = 0.011; rs401681, OR = 0.85, 95% CI = 0.74–0.99, P = 0.034). Furthermore, we observed higher CLPTM1L messenger RNA levels in fetal mesenchymal stem cells from the rs2735845 G allele carriers compared with that from non-carriers. In addition, using an immunohistochemistry assay, we observed higher TERT and CLPTM1L levels in NPC tissues compared with that in non-cancerous nasopharyngeal tissues. Our findings suggest that polymorphisms in the TERT-CLPTM1L locus may play a role in mediating the susceptibility to NPC in Chinese populations.",2015 Nov 26,"['Zhang, Yang', 'Zhang, Xiaoai', 'Zhang, Hongxing', 'Zhai, Yun', 'Wang, Zhifu', 'Li, Peiyao', 'Yu, Lixia', 'Xia, Xia', 'Zhang, Ying', 'Zeng, Yixin', 'He, Fuchu', 'Zhou, Gangqiao']",Oncotarget,,,True
e9dfffbed92e23efc7241bae7623b4584f50b69e,PMC,Global Strategies for the Prevention and Control of Infectious Diseases and Non-Communicable Diseases,http://dx.doi.org/10.2188/jea.JE20160010,PMC4808683,26947953,CC BY,"This article on global health reviews the environment surrounding health strategies and plans, as well as lessons learned from the first 15 years of the 21st century, followed by a discussion on the quest for a new paradigm for disease control efforts and challenges and opportunities for Japan.",2016 Apr 5,"Nakatani, Hiroki",J Epidemiol,,,True
ca52af941437873b4122bb2e26d7e3fab81cd73f,PMC,Activation of the DNA Damage Response by RNA Viruses,http://dx.doi.org/10.3390/biom6010002,PMC4808796,26751489,CC BY,"RNA viruses are a genetically diverse group of pathogens that are responsible for some of the most prevalent and lethal human diseases. Numerous viruses introduce DNA damage and genetic instability in host cells during their lifecycles and some species also manipulate components of the DNA damage response (DDR), a complex and sophisticated series of cellular pathways that have evolved to detect and repair DNA lesions. Activation and manipulation of the DDR by DNA viruses has been extensively studied. It is apparent, however, that many RNA viruses can also induce significant DNA damage, even in cases where viral replication takes place exclusively in the cytoplasm. DNA damage can contribute to the pathogenesis of RNA viruses through the triggering of apoptosis, stimulation of inflammatory immune responses and the introduction of deleterious mutations that can increase the risk of tumorigenesis. In addition, activation of DDR pathways can contribute positively to replication of viral RNA genomes. Elucidation of the interactions between RNA viruses and the DDR has provided important insights into modulation of host cell functions by these pathogens. This review summarises the current literature regarding activation and manipulation of the DDR by several medically important RNA viruses.",2016 Jan 6,"['Ryan, Ellis L.', 'Hollingworth, Robert', 'Grand, Roger J.']",Biomolecules,,,True
96464179873570564cc07be6219abb043caad44a,PMC,Modeling Heterogeneity in Direct Infectious Disease Transmission in a Compartmental Model,http://dx.doi.org/10.3390/ijerph13030253,PMC4808916,26927140,CC BY,"Mathematical models have been used to understand the transmission dynamics of infectious diseases and to assess the impact of intervention strategies. Traditional mathematical models usually assume a homogeneous mixing in the population, which is rarely the case in reality. Here, we construct a new transmission function by using as the probability density function a negative binomial distribution, and we develop a compartmental model using it to model the heterogeneity of contact rates in the population. We explore the transmission dynamics of the developed model using numerical simulations with different parameter settings, which characterize different levels of heterogeneity. The results show that when the reproductive number, [Formula: see text] , is larger than one, a low level of heterogeneity results in dynamics similar to those predicted by the homogeneous mixing model. As the level of heterogeneity increases, the dynamics become more different. As a test case, we calibrated the model with the case incidence data for severe acute respiratory syndrome (SARS) in Beijing in 2003, and the estimated parameters demonstrated the effectiveness of the control measures taken during that period.",2016 Mar 24,"['Kong, Lingcai', 'Wang, Jinfeng', 'Han, Weiguo', 'Cao, Zhidong']",Int J Environ Res Public Health,,,True
5153d1fa1f68741534152792b0b6b15e2dcf4490,PMC,"Erratum: Li, M., et al. Middle East Respiratory Syndrome and Medical Students: Letter from China. Int. J. Environ. Res. Public Health 2015, 12, 13289–13294",http://dx.doi.org/10.3390/ijerph13030335,PMC4808998,26999182,CC BY,,2016 Mar 18,,Int J Environ Res Public Health,,,False
b8ee195be637c05754e714310c9d0d5ba715d683,PMC,"Overview of Infectious Disease Surveillance System in Japan, 1999-2005",http://dx.doi.org/10.2188/jea.17.S3,PMC4809251,18239339,CC BY,"BACKGROUND: In 1999 the Communicable Disease Prevention Law of Japan was completely revised into the ""New"" Infectious Disease Control Law, which reiterated the importance of surveillance and information dissemination and re-organized the surveillance system. This paper is an attempt to illustrate the potential impact of the new surveillance system through a description of the existing surveillance system and data before and after the revision. METHODS: After a historical review of surveillance system in Japan, the current surveillance system is described. Data sets of actual case numbers reported and incidence rate per 1,000,000 population are compared before and after the revision. RESULTS: Comparison of the data between the 2 periods revealed that most of the diseases have had declining trends after the new law was enacted with several exceptions. However, although no major break in continuity is observed in seriously perceived disease, in milder diseases there are striking gaps between the numbers reported in the mandatory and sentinel reporting framework. Sentinel reporting framework maintained the continuity of data without major gaps. CONCLUSIONS: From this perspective, the new surveillance system with two different frameworks of mandatory reporting for severe diseases and sentinel reporting for milder diseases seems to be working well. But continuous efforts should be made for evaluation and improvement of surveillance system and risk communication through the research on data analysis and effective communication method.",2008 Jan 30,"['Taniguchi, Kiyosu', 'Hashimoto, Shuji', 'Kawado, Miyuki', 'Murakami, Yoshitaka', 'Izumida, Michiko', 'Ohta, Akiko', 'Tada, Yuki', 'Shigematsu, Mika', 'Yasui, Yoshinori', 'Nagai, Masaki']",J Epidemiol,,,True
5df6b1ce03de2b78801de3d8e20a50b3563a2cf4,PMC,Viral Interactions with PDZ Domain-Containing Proteins—An Oncogenic Trait?,http://dx.doi.org/10.3390/pathogens5010008,PMC4810129,26797638,CC BY,"Many of the human viruses with oncogenic capabilities, either in their natural host or in experimental systems (hepatitis B and C, human T cell leukaemia virus type 1, Kaposi sarcoma herpesvirus, human immunodeficiency virus, high-risk human papillomaviruses and adenovirus type 9), encode in their limited genome the ability to target cellular proteins containing PSD95/ DLG/ZO-1 (PDZ) interaction modules. In many cases (but not always), the viruses have evolved to bind the PDZ domains using the same short linear peptide motifs found in host protein-PDZ interactions, and in some cases regulate the interactions in a similar fashion by phosphorylation. What is striking is that the diverse viruses target a common subset of PDZ proteins that are intimately involved in controlling cell polarity and the structure and function of intercellular junctions, including tight junctions. Cell polarity is fundamental to the control of cell proliferation and cell survival and disruption of polarity and the signal transduction pathways involved is a key event in tumourigenesis. This review focuses on the oncogenic viruses and the role of targeting PDZ proteins in the virus life cycle and the contribution of virus-PDZ protein interactions to virus-mediated oncogenesis. We highlight how many of the viral associations with PDZ proteins lead to deregulation of PI3K/AKT signalling, benefitting virus replication but as a consequence also contributing to oncogenesis.",2016 Jan 18,"['James, Claire D.', 'Roberts, Sally']",Pathogens,,,True
021144f6c1945b9bff9ea9e4b04b24dcf53330b4,PMC,Identification and Comparison of Receptor Binding Characteristics of the Spike Protein of Two Porcine Epidemic Diarrhea Virus Strains,http://dx.doi.org/10.3390/v8030055,PMC4810246,26907329,CC BY,"Porcine epidemic diarrhea virus (PEDV), a member of Alphacoronavirus, has caused huge economic losses for the global pork industry recently. The spike (S) protein mediates PEDV entry into host cells. Herein, we investigated the interactions between the S protein and its receptor porcine aminopeptidase N (pAPN) or co-receptor sugars. The C-terminal domain (CTD) of the S1 domain is bound to pAPN. The prototype strain demonstrated similar receptor-binding activity compared with the variant field isolate. Three loops at the tips of the β-barrel domains did not play crucial roles in the PEDV S-pAPN association, indicating that PEDV conforms to a different receptor recognition model compared with transmissible gastroenteritis virus (TGEV), porcine respiratory CoV (PRCV), and human coronavirus NL63 (HCoV-NL63). The N-terminal domain (NTD) of the PEDV S1 domain could bind sugar, a possible co-receptor for PEDV. The prototype strain exhibited weaker sugar-binding activity compared with the variant field isolate. Strategies targeting the receptor binding domain (RBD) may be helpful for developing vaccines or antiviral drugs for PEDV. Understanding the differences in receptor binding between the prototype and the variant strains may provide insight into PEDV pathogenesis.",2016 Feb 23,"['Deng, Feng', 'Ye, Gang', 'Liu, Qianqian', 'Navid, Muhammad Tariq', 'Zhong, Xiaoli', 'Li, Youwen', 'Wan, Chunyun', 'Xiao, Shaobo', 'He, Qigai', 'Fu, Zhen F.', 'Peng, Guiqing']",Viruses,,,True
4b81c74ca2592fb4e3e81f9013a98fe890cb42e4,PMC,Identification and Comparison of Receptor Binding Characteristics of the Spike Protein of Two Porcine Epidemic Diarrhea Virus Strains,http://dx.doi.org/10.3390/v8030055,PMC4810246,26907329,CC BY,"Porcine epidemic diarrhea virus (PEDV), a member of Alphacoronavirus, has caused huge economic losses for the global pork industry recently. The spike (S) protein mediates PEDV entry into host cells. Herein, we investigated the interactions between the S protein and its receptor porcine aminopeptidase N (pAPN) or co-receptor sugars. The C-terminal domain (CTD) of the S1 domain is bound to pAPN. The prototype strain demonstrated similar receptor-binding activity compared with the variant field isolate. Three loops at the tips of the β-barrel domains did not play crucial roles in the PEDV S-pAPN association, indicating that PEDV conforms to a different receptor recognition model compared with transmissible gastroenteritis virus (TGEV), porcine respiratory CoV (PRCV), and human coronavirus NL63 (HCoV-NL63). The N-terminal domain (NTD) of the PEDV S1 domain could bind sugar, a possible co-receptor for PEDV. The prototype strain exhibited weaker sugar-binding activity compared with the variant field isolate. Strategies targeting the receptor binding domain (RBD) may be helpful for developing vaccines or antiviral drugs for PEDV. Understanding the differences in receptor binding between the prototype and the variant strains may provide insight into PEDV pathogenesis.",2016 Feb 23,"['Deng, Feng', 'Ye, Gang', 'Liu, Qianqian', 'Navid, Muhammad Tariq', 'Zhong, Xiaoli', 'Li, Youwen', 'Wan, Chunyun', 'Xiao, Shaobo', 'He, Qigai', 'Fu, Zhen F.', 'Peng, Guiqing']",Viruses,,,False
685efeb0ad4c214b8295dc4f723c3269464772d8,PMC,Isolation of a Novel Fusogenic Orthoreovirus from Eucampsipoda africana Bat Flies in South Africa,http://dx.doi.org/10.3390/v8030065,PMC4810255,27011199,CC BY,"We report on the isolation of a novel fusogenic orthoreovirus from bat flies (Eucampsipoda africana) associated with Egyptian fruit bats (Rousettus aegyptiacus) collected in South Africa. Complete sequences of the ten dsRNA genome segments of the virus, tentatively named Mahlapitsi virus (MAHLV), were determined. Phylogenetic analysis places this virus into a distinct clade with Baboon orthoreovirus, Bush viper reovirus and the bat-associated Broome virus. All genome segments of MAHLV contain a 5' terminal sequence (5'-GGUCA) that is unique to all currently described viruses of the genus. The smallest genome segment is bicistronic encoding for a 14 kDa protein similar to p14 membrane fusion protein of Bush viper reovirus and an 18 kDa protein similar to p16 non-structural protein of Baboon orthoreovirus. This is the first report on isolation of an orthoreovirus from an arthropod host associated with bats, and phylogenetic and sequence data suggests that MAHLV constitutes a new species within the Orthoreovirus genus.",2016 Feb 29,"['Jansen van Vuren, Petrus', 'Wiley, Michael', 'Palacios, Gustavo', 'Storm, Nadia', 'McCulloch, Stewart', 'Markotter, Wanda', 'Birkhead, Monica', 'Kemp, Alan', 'Paweska, Janusz T.']",Viruses,,,True
70948646d2777b7a433c7558b5c3488bdb77e526,PMC,Roles of the Picornaviral 3C Proteinase in the Viral Life Cycle and Host Cells,http://dx.doi.org/10.3390/v8030082,PMC4810272,26999188,CC BY,"The Picornaviridae family comprises a large group of non-enveloped viruses that have a major impact on human and veterinary health. The viral genome contains one open reading frame encoding a single polyprotein that can be processed by viral proteinases. The crucial 3C proteinases (3C(pro)s) of picornaviruses share similar spatial structures and it is becoming apparent that 3C(pro) plays a significant role in the viral life cycle and virus host interaction. Importantly, the proteinase and RNA-binding activity of 3C(pro) are involved in viral polyprotein processing and the initiation of viral RNA synthesis. In addition, 3C(pro) can induce the cleavage of certain cellular factors required for transcription, translation and nucleocytoplasmic trafficking to modulate cell physiology for viral replication. Due to interactions between 3C(pro) and these essential factors, 3C(pro) is also involved in viral pathogenesis to support efficient infection. Furthermore, based on the structural conservation, the development of irreversible inhibitors and discovery of non-covalent inhibitors for 3C(pro) are ongoing and a better understanding of the roles played by 3C(pro) may provide insights into the development of potential antiviral treatments. In this review, the current knowledge regarding the structural features, multiple functions in the viral life cycle, pathogen host interaction, and development of antiviral compounds for 3C(pro) is summarized.",2016 Mar 17,"['Sun, Di', 'Chen, Shun', 'Cheng, Anchun', 'Wang, Mingshu']",Viruses,,,True
6da13d90743ba52bded6ed06e214541ba19d5078,PMC,Discovery of Novel Alphacoronaviruses in European Rodents and Shrews,http://dx.doi.org/10.3390/v8030084,PMC4810274,27102167,CC BY,"Eight hundred and thirteen European rodents and shrews encompassing seven different species were screened for alphacoronaviruses using PCR detection. Novel alphacoronaviruses were detected in the species Rattus norvegicus, Microtus agrestis, Sorex araneus and Myodes glareolus. These, together with the recently described Lucheng virus found in China, form a distinct rodent/shrew-specific clade within the coronavirus phylogeny. Across a highly conserved region of the viral polymerase gene, the new members of this clade were up to 22% dissimilar at the nucleotide level to the previously described Lucheng virus. As such they might represent distinct species of alphacoronaviruses. These data greatly extend our knowledge of wildlife reservoirs of alphacoronaviruses.",2016 Mar 18,"['Tsoleridis, Theocharis', 'Onianwa, Okechukwu', 'Horncastle, Emma', 'Dayman, Emma', 'Zhu, Miaoran', 'Danjittrong, Taechasit', 'Wachtl, Marta', 'Behnke, Jerzy M.', 'Chapman, Sarah', 'Strong, Victoria', 'Dobbs, Phillipa', 'Ball, Jonathan K.', 'Tarlinton, Rachael E.', 'McClure, C. Patrick']",Viruses,,,True
e01d6fcf286c7231445ac9db61237ac71ca26fec,PMC,"Porcine Sapelovirus Uses α2,3-Linked Sialic Acid on GD1a Ganglioside as a Receptor",http://dx.doi.org/10.1128/JVI.02449-15,PMC4810533,26865725,CC BY,"The receptor(s) for porcine sapelovirus (PSV), which causes diarrhea, pneumonia, polioencephalomyelitis, and reproductive disorders in pigs, remains largely unknown. Given the precedent for other picornaviruses which use terminal sialic acids (SAs) as receptors, we examined the role of SAs in PSV binding and infection. Using a variety of approaches, including treating cells with a carbohydrate-destroying chemical (NaIO(4)), mono- or oligosaccharides (N-acetylneuraminic acid, galactose, and 6′-sialyllactose), linkage-specific sialidases (neuraminidase and sialidase S), lectins (Maakia amurensis lectin and Sambucus nigra lectin), proteases (trypsin and chymotrypsin), and glucosylceramide synthase inhibitors (dl-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol and phospholipase C), we demonstrated that PSV could recognize α2,3-linked SA on glycolipids as a receptor. On the other hand, PSVs had no binding affinity for synthetic histo-blood group antigens (HBGAs), suggesting that PSVs could not use HBGAs as receptors. Depletion of cell surface glycolipids followed by reconstitution studies indicated that GD1a ganglioside, but not other gangliosides, could restore PSV binding and infection, further confirming α2,3-linked SA on GD1a as a PSV receptor. Our results could provide significant information on the understanding of the life cycle of sapelovirus and other picornaviruses. For the broader community in the area of pathogens and pathogenesis, these findings and insights could contribute to the development of affordable, useful, and efficient drugs for anti-sapelovirus therapy. IMPORTANCE The porcine sapelovirus (PSV) is known to cause enteritis, pneumonia, polioencephalomyelitis, and reproductive disorders in pigs. However, the receptor(s) that the PSV utilizes to enter host cells remains largely unknown. Using a variety of approaches, we showed that α2,3-linked terminal sialic acid (SA) on the cell surface GD1a ganglioside could be used for PSV binding and infection as a receptor. On the other hand, histo-blood group antigens also present in the cell surface carbohydrates could not be utilized as PSV receptors for binding and infection. These findings should contribute to the understanding of the sapelovirus life cycle and to the development of affordable, useful and efficient drugs for anti-sapelovirus therapy.",2016 Mar 28,"['Kim, Deok-Song', 'Son, Kyu-Yeol', 'Koo, Kyung-Min', 'Kim, Ji-Yun', 'Alfajaro, Mia Madel', 'Park, Jun-Gyu', 'Hosmillo, Myra', 'Soliman, Mahmoud', 'Baek, Yeong-Bin', 'Cho, Eun-Hyo', 'Lee, Ju-Hwan', 'Kang, Mun-Il', 'Goodfellow, Ian', 'Cho, Kyoung-Oh']",J Virol,,,True
281303193aa29253bb0b00328b48e892d0cf4f85,PMC,Low-Fidelity Polymerases of Alphaviruses Recombine at Higher Rates To Overproduce Defective Interfering Particles,http://dx.doi.org/10.1128/JVI.02921-15,PMC4810721,26676773,CC BY,"Low-fidelity RNA-dependent RNA polymerases for many RNA virus mutators have been shown to confer attenuated phenotypes, presumably due to increased mutation rates. Additionally, for many RNA viruses, replication to high titers results in the production of defective interfering particles (DIs) that also attenuate infection. We hypothesized that fidelity, recombination, and DI production are tightly linked. We show that a Sindbis virus mutator replicating at a high multiplicity of infection manifests an earlier and greater accumulation of DIs than its wild-type counterpart. The isolated DIs interfere with the replication of full-length virus in a dose-dependent manner. Importantly, the ability of the mutator virus to overproduce DIs could be linked to an increased recombination frequency. These data confirm that RNA-dependent RNA polymerase fidelity and recombination are inversely correlated for this mutator. Our findings suggest that defective interference resulting from higher recombination rates may be more detrimental to RNA virus mutators than the increase in mutational burden. IMPORTANCE Replication, adaptation, and evolution of RNA viruses rely in large part on their low-fidelity RNA-dependent RNA polymerase. Viruses artificially modified in their polymerases to decrease fidelity (mutator viruses) are attenuated in vivo, demonstrating the important role of fidelity in viral fitness. However, attenuation was attributed solely to the modification of the viral mutation rate and the accumulation of detrimental point mutations. In this work, we described an additional phenotype of mutator viruses: an increased recombination rate leading to defective interfering particle (DI) overproduction. Because DIs are known for their inhibitory effect on viral replication, our work suggests that fidelity variants may be attenuated in vivo via several mechanisms. This has important implications in the development of fidelity variants as live attenuated vaccine strains.",2016 Feb 11,"['Poirier, Enzo Z.', 'Mounce, Bryan C.', 'Rozen-Gagnon, Kathryn', 'Hooikaas, Peter Jan', 'Stapleford, Kenneth A.', 'Moratorio, Gonzalo', 'Vignuzzi, Marco']",J Virol,,,True
2d85ecf540b138ba2c5dd735bcf986c58ede052e,PMC,"Ethanol Extract of Sanguisorbae Radix Inhibits Mast Cell Degranulation and Suppresses 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions",http://dx.doi.org/10.1155/2016/2947390,PMC4811174,27065570,CC BY,"Sanguisorbae Radix (SR) is well known as herbal medicine named “Zi-Yu” in Korea, which is the dried roots of Sanguisorba officinalis L. (Rosacease). We investigated the underlying mechanism on the inhibition of atopic dermatitis (AD) of an ethanol extract of SR (ESR) using 2,4-dinitrochlorobenzene- (DNCB-) induced AD mice model. Oral administration of ESR significantly suppressed DNCB-induced AD-like symptoms such as scratching behavior, ear thickness, epidermal thickness, and IgE levels. To investigate the effects of ESR treatment on degranulation of IgE/Ag-activated mouse bone marrow-derived mast cells (BMMCs), we measured the release of β-hexosaminidase (β-HEX, degranulation marker). ESR decreased the infiltration of eosinophils and mast cells into the AD skin lesions. Furthermore, ESR significantly inhibited degranulation of IgE/Ag-activated BMMCs. We have demonstrated that ESR decreased AD symptoms in mice and inhibits degranulation of IgE/Ag-activated mast cells. Our study suggests that ESR may serve as a potential therapeutic candidate for the treatment of AD symptoms.",2016 Mar 15,"['Yang, Ju-Hye', 'Yoo, Jae-Myung', 'Cho, Won-Kyung', 'Ma, Jin Yeul']",Mediators Inflamm,,,True
398cbb196acb9f8ee91a22edcca3b32c044878b8,PMC,Evolutionary reversion of live viral vaccines: Can genetic engineering subdue it?,http://dx.doi.org/10.1093/ve/vev005,PMC4811365,27034780,CC BY,"Attenuated, live viral vaccines have been extraordinarily successful in protecting against many diseases. The main drawbacks in their development and use have been reliance on an unpredictable method of attenuation and the potential for evolutionary reversion to high virulence. Methods of genetic engineering now provide many safer alternatives to live vaccines, so if live vaccines are to compete with these alternatives in the future, they must either have superior immunogenicity or they must be able to overcome these former disadvantages. Several live vaccine designs that were historically inaccessible are now feasible because of advances in genome synthesis. Some of those methods are addressed here, with an emphasis on whether they enable predictable levels of attenuation and whether they are stable against evolutionary reversion. These new designs overcome many of the former drawbacks and position live vaccines to be competitive with alternatives. Not only do new methods appear to retard evolutionary reversion enough to prevent vaccine-derived epidemics, but it may even be possible to permanently attenuate live vaccines that are transmissible but cannot evolve to higher virulence under prolonged adaptation.",2015 Jul 31,"Bull, J. J.",Virus Evol,,,True
434ab543a48b7fb395d181ffb947814bd1b506c4,PMC,The Roles of Histidines and Charged Residues as Potential Triggers of a Conformational Change in the Fusion Loop of Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.pone.0152527,PMC4811418,27023721,CC BY,"Ebola virus (EBOV) enters cells from late endosomes/lysosomes under mildly acidic conditions. Entry by fusion with the endosomal membrane requires the fusion loop (FL, residues 507–560) of the EBOV surface glycoprotein to undergo a pH-dependent conformational change. To find the pH trigger for this reaction we mutated multiple conserved histidines and charged and uncharged hydrophilic residues in the FL and measured their activity by liposome fusion and cell entry of virus-like particles. The FL location in the membrane was assessed by NMR using soluble and lipid-bound paramagnetic relaxation agents. While we could not identify a single residue to be alone responsible for pH triggering, we propose that a distributed pH effect over multiple residues induces the conformational change that enhances membrane insertion and triggers the fusion activity of the EBOV FL.",2016 Mar 29,"['Lee, Jinwoo', 'Gregory, Sonia M.', 'Nelson, Elizabeth A.', 'White, Judith M.', 'Tamm, Lukas K.']",PLoS One,,,True
c3e58660ecf2f667fb13b113859dba3a87ef36fe,PMC,Translation of Korean Medicine Use to ICD-Codes Using National Health Insurance Service-National Sample Cohort,http://dx.doi.org/10.1155/2016/8160838,PMC4812360,27069494,CC BY,"Background. Korean medicine was incorporated into the Korean Classification of Diseases (KCD) 6 through the development of U codes (U20–U99). Studies of the burden of disease have used summary measures such as disability-adjusted life years. Although Korean medicine is included in the official health care system, studies of the burden of disease that include Korean medicine are lacking. Methods. A data-based approach was used with National Health Insurance Service-National Sample Cohort data for the year 2012. U code diagnoses for patients covered by National Health Insurance were collected. Using the main disease and subdisease codes, the proportion of U codes was redistributed into the related KCD 6 codes and visualized. U code and KCD code relevance was appraised prior to the analysis by consultation with medical professionals and from the beta draft version of the International Classification of Diseases-11 traditional medicine chapter. Results. This approach enabled redistribution of U codes into KCD 6 codes. Musculoskeletal diseases had the greatest increase in the burden of disease through this approach. Conclusion. This study provides a possible method of incorporating Korean medicine into burden of disease analyses through a data-based approach. Further studies should analyze potential yearly differences.",2016 Mar 16,"['Lee, Ye-Seul', 'Lee, Ye-Rin', 'Chae, Younbyoung', 'Park, So-Youn', 'Oh, In-Hwan', 'Jang, Bo-Hyoung']",Evid Based Complement Alternat Med,,,True
eb0a05f4e7d9d276e308e8f6e80617962b07f9cb,PMC,"Molecular Selection, Modification and Development of Therapeutic Oligonucleotide Aptamers",http://dx.doi.org/10.3390/ijms17030358,PMC4813219,26978355,CC BY,"Monoclonal antibodies are the dominant agents used in inhibition of biological target molecules for disease therapeutics, but there are concerns of immunogenicity, production, cost and stability. Oligonucleotide aptamers have comparable affinity and specificity to targets with monoclonal antibodies whilst they have minimal immunogenicity, high production, low cost and high stability, thus are promising inhibitors to rival antibodies for disease therapy. In this review, we will compare the detailed advantages and disadvantages of antibodies and aptamers in therapeutic applications and summarize recent progress in aptamer selection and modification approaches. We will present therapeutic oligonucleotide aptamers in preclinical studies for skeletal diseases and further discuss oligonucleotide aptamers in different stages of clinical evaluation for various disease therapies including macular degeneration, cancer, inflammation and coagulation to highlight the bright commercial future and potential challenges of therapeutic oligonucleotide aptamers.",2016 Mar 11,"['Yu, Yuanyuan', 'Liang, Chao', 'Lv, Quanxia', 'Li, Defang', 'Xu, Xuegong', 'Liu, Baoqin', 'Lu, Aiping', 'Zhang, Ge']",Int J Mol Sci,,,True
5f3f613be264f8b10318dfe8e92777fe7a95848e,PMC,Human Sentinel Surveillance of Influenza and Other Respiratory Viral Pathogens in Border Areas of Western Cambodia,http://dx.doi.org/10.1371/journal.pone.0152529,PMC4814059,27028323,CC0,"Little is known about circulation of influenza and other respiratory viruses in remote populations along the Thai-Cambodia border in western Cambodia. We screened 586 outpatients (median age 5, range 1–77) presenting with influenza-like-illness (ILI) at 4 sentinel sites in western Cambodia between May 2010 and December 2012. Real-time reverse transcriptase (rRT) PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis. ILI-specimens negative for influenza were cultured, followed by rRT-PCR for enterovirus and rhinovirus (EV/RV) and EV71. Influenza was found in 168 cases (29%) and occurred almost exclusively in the rainy season from June to November. Isolated influenza strains had close antigenic and phylogenetic relationships, matching vaccine and circulating strains found elsewhere in Cambodia. Influenza vaccination coverage was low (<20%). Western Cambodian H1N1(2009) isolate genomes were more closely related to 10 earlier Cambodia isolates (94.4% genome conservation) than to 13 Thai isolates (75.9% genome conservation), despite sharing the majority of the amino acid changes with the Thai references. Most genes showed signatures of purifying selection. Viral culture detected only adenovirus (5.7%) and parainfluenza virus (3.8%), while non-polio enteroviruses (10.3%) were detected among 164 culture-negative samples including coxsackievirus A4, A6, A8, A9, A12, B3, B4 and echovirus E6 and E9 using nested RT-PCR methods. A single specimen of EV71 was found. Despite proximity to Thailand, influenza epidemiology of these western Cambodian isolates followed patterns observed elsewhere in Cambodia, continuing to support current vaccine and treatment recommendations from the Cambodian National Influenza Center. Amino acid mutations at non-epitope sites, particularly hemagglutinin genes, require further investigation in light of an increasingly important role of permissive mutations in influenza virus evolution. Further research about the burden of adenovirus and non-polio enteroviruses as etiologic agents in acute respiratory infections in Cambodia is also needed.",2016 Mar 30,"['Timmermans, Ans', 'Melendrez, Melanie C.', 'Se, Youry', 'Chuang, Ilin', 'Samon, Nou', 'Uthaimongkol, Nichapat', 'Klungthong, Chonticha', 'Manasatienkij, Wudtichai', 'Thaisomboonsuk, Butsaya', 'Tyner, Stuart D.', 'Rith, Sareth', 'Horm, Viseth Srey', 'Jarman, Richard G.', 'Bethell, Delia', 'Chanarat, Nitima', 'Pavlin, Julie', 'Wongstitwilairoong, Tippa', 'Saingam, Piyaporn', 'El, But Sam', 'Fukuda, Mark M.', 'Touch, Sok', 'Sovann, Ly', 'Fernandez, Stefan', 'Buchy, Philippe', 'Chanthap, Lon', 'Saunders, David']",PLoS One,,,True
68493ffac48a4fdbc15314a0a2bf5cabd087f853,PMC,The Hemagglutinin of Bat-Associated Influenza Viruses Is Activated by TMPRSS2 for pH-Dependent Entry into Bat but Not Human Cells,http://dx.doi.org/10.1371/journal.pone.0152134,PMC4814062,27028521,CC BY,"New World bats have recently been discovered to harbor influenza A virus (FLUAV)-related viruses, termed bat-associated influenza A-like viruses (batFLUAV). The internal proteins of batFLUAV are functional in mammalian cells. In contrast, no biological functionality could be demonstrated for the surface proteins, hemagglutinin (HA)-like (HAL) and neuraminidase (NA)-like (NAL), and these proteins need to be replaced by their human counterparts to allow spread of batFLUAV in human cells. Here, we employed rhabdoviral vectors to study the role of HAL and NAL in viral entry. Vectors pseudotyped with batFLUAV-HAL and -NAL were able to enter bat cells but not cells from other mammalian species. Host cell entry was mediated by HAL and was dependent on prior proteolytic activation of HAL and endosomal low pH. In contrast, sialic acids were dispensable for HAL-driven entry. Finally, the type II transmembrane serine protease TMPRSS2 was able to activate HAL for cell entry indicating that batFLUAV can utilize human proteases for HAL activation. Collectively, these results identify viral and cellular factors governing host cell entry driven by batFLUAV surface proteins. They suggest that the absence of a functional receptor precludes entry of batFLUAV into human cells while other prerequisites for entry, HAL activation and protonation, are met in target cells of human origin.",2016 Mar 30,"['Hoffmann, Markus', 'Krüger, Nadine', 'Zmora, Pawel', 'Wrensch, Florian', 'Herrler, Georg', 'Pöhlmann, Stefan']",PLoS One,,,True
c10d2b72f8d450209946e805ba18154c9a6c5f7f,PMC,Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor,http://dx.doi.org/10.1371/journal.ppat.1005531,PMC4814111,27027316,CC BY,"Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV). The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro) with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for further development for important coronaviruses in animals and humans.",2016 Mar 30,"['Kim, Yunjeong', 'Liu, Hongwei', 'Galasiti Kankanamalage, Anushka C.', 'Weerasekara, Sahani', 'Hua, Duy H.', 'Groutas, William C.', 'Chang, Kyeong-Ok', 'Pedersen, Niels C.']",PLoS Pathog,,,True
7bb64d780ff05f2e1ab0a912fdb77aca44652871,PMC,Mycoplasma pneumoniae: Current Knowledge on Nucleic Acid Amplification Techniques and Serological Diagnostics,http://dx.doi.org/10.3389/fmicb.2016.00448,PMC4814781,27064893,CC BY,"Mycoplasma pneumoniae (M. pneumoniae) belongs to the class Mollicutes and has been recognized as a common cause of respiratory tract infections (RTIs), including community-acquired pneumonia (CAP), that occur worldwide and in all age groups. In addition, M. pneumoniae can simultaneously or sequentially lead to damage in the nervous system and has been associated with a wide variety of other acute and chronic diseases. During the past 10 years, the proportion of LRTI in children and adults, associated with M. pneumoniae infection has ranged from 0 to more than 50%. This variation is due to the age and the geographic location of the population examined but also due to the diagnostic methods used. The true role of M. pneumoniae in RTIs remains a challenge given the many limitations and lack of standardization of the applied diagnostic tool in most cases, with resultant wide variations in data from different studies. Correct and rapid diagnosis and/or management of M. pneumoniae infections is, however, critical to initiate appropriate antibiotic treatment and is nowadays usually done by PCR and/or serology. Several recent reviews, have summarized current methods for the detection and identification of M. pneumoniae. This review will therefore provide a look at the general principles, advantages, diagnostic value, and limitations of the most currently used detection techniques for the etiological diagnosis of a M. pneumoniae infection as they evolve from research to daily practice.",2016 Mar 31,"['Loens, Katherine', 'Ieven, Margareta']",Front Microbiol,,,True
ac04992c38f8d8bb758a7460e350827c390698a1,PMC,Clinical outcomes in outpatient respiratory syncytial virus infection in immunocompromised children,http://dx.doi.org/10.1111/irv.12375,PMC4814860,26859306,CC BY,"BACKGROUND: Immunocompromised patients are at high risk for morbidity and mortality due to respiratory syncytial virus (RSV) infection. Increasingly, pediatric patients with malignancy or undergoing transplantation are managed primarily as outpatients. Data regarding the clinical presentation and outcomes of RSV in the outpatient pediatric immunocompromised population are limited. METHODS: We performed a retrospective cohort study of children with hematologic malignancy or hematopoietic or solid organ transplant with laboratory‐confirmed RSV infection diagnosed as outpatients at an academic medical center between 2008 and 2013. RESULTS: Of 54 patients with RSV detected while outpatients, 15 (28%) were hospitalized, 7 (13%) received ribavirin, and one (2%) received intravenous immunoglobulin. One (2%) patient was critically ill, but there were no deaths due to RSV infection. Fever (P < 0·01) was associated with increased risk of hospitalization. CONCLUSIONS: Most immunocompromised children with RSV detected while outpatients did not require hospitalization or receive antiviral treatment. Potential studies of RSV therapies should consider inclusion of patients in an ambulatory setting.",2016 May 23,"['Chu, Helen Y.', 'Chin, Jennifer', 'Pollard, Jessica', 'Zerr, Danielle M.', 'Englund, Janet A.']",Influenza Other Respir Viruses,,,True
0b0ce0d563375eba593f552fc31f82289982c829,PMC,"Surveillance for severe acute respiratory infections in Southern Arizona, 2010–2014",http://dx.doi.org/10.1111/irv.12360,PMC4814863,26590069,CC BY,"BACKGROUND: The Binational Border Infectious Disease Surveillance program began surveillance for severe acute respiratory infections (SARI) on the US–Mexico border in 2009. Here, we describe patients in Southern Arizona. METHODS: Patients admitted to five acute care hospitals that met the SARI case definition (temperature ≥37·8°C or reported fever or chills with history of cough, sore throat, or shortness of breath in a hospitalized person) were enrolled. Staff completed a standard form and collected a nasopharyngeal swab which was tested for selected respiratory viruses by reverse transcription polymerase chain reaction. RESULTS: From October 2010–September 2014, we enrolled 332 SARI patients. Fifty‐two percent were male and 48% were white non‐Hispanic. The median age was 63 years (47% ≥65 years and 5·2% <5 years). During hospitalization, 51 of 230 (22%) patients required intubation, 120 of 297 (40%) were admitted to intensive care unit, and 28 of 278 (10%) died. Influenza vaccination was 56%. Of 309 cases tested, 49 (16%) were positive for influenza viruses, 25 (8·1%) for human metapneumovirus, 20 (6·5%) for parainfluenza viruses, 16 (5·2%) for coronavirus, 11 (3·6%) for respiratory syncytial virus, 10 (3·2%) for rhinovirus, 4 (1·3%) for rhinovirus/enterovirus, 3 (1·0%) for enteroviruses, and 3 (1·0%) for adenovirus. Among the 49 influenza‐positive specimens, 76% were influenza A (19 H3N2, 17 H1N1pdm09, and 1 not subtyped), and 24% were influenza B. CONCLUSION: Influenza viruses were a frequent cause of SARI in hospitalized patients in Southern Arizona. Monitoring respiratory illness in border populations will help better understand the etiologies. Improving influenza vaccination coverage may help prevent some SARI cases.",2016 May 29,"['Wansaula, Zimy', 'Olsen, Sonja J.', 'Casal, Mariana G.', 'Golenko, Catherine', 'Erhart, Laura M.', 'Kammerer, Peter', 'Whitfield, Natalie', 'McCotter, Orion Z.']",Influenza Other Respir Viruses,,,True
8233e375e79b4e93b9d9a614d44762dba52b342f,PMC,Serotype and genetic diversity of human rhinovirus strains that circulated in Kenya in 2008,http://dx.doi.org/10.1111/irv.12373,PMC4814864,26822469,CC BY,"BACKGROUND: Human rhinoviruses (HRVs) are a well‐established cause of the common cold and recent studies indicated that they may be associated with severe acute respiratory illnesses (SARIs) like pneumonia, asthma, and bronchiolitis. Despite global studies on the genetic diversity of the virus, the serotype diversity of these viruses across diverse geographic regions in Kenya has not been characterized. OBJECTIVES: This study sought to characterize the serotype diversity of HRV strains that circulated in Kenya in 2008. METHODS: A total of 517 archived nasopharyngeal samples collected in a previous respiratory virus surveillance program across Kenya in 2008 were selected. Participants enrolled were outpatients who presented with influenza‐like (ILI) symptoms. Real‐time RT‐PCR was employed for preliminary HRV detection. HRV‐positive samples were amplified using RT‐PCR and thereafter the nucleotide sequences of the amplicons were determined followed by phylogenetic analysis. RESULTS: Twenty‐five percent of the samples tested positive for HRV. Phylogenetic analysis revealed that the Kenyan HRVs clustered into three main species comprising HRV‐A (54%), HRV‐B (12%), and HRV‐C (35%). Overall, 20 different serotypes were identified. Intrastrain sequence homology among the Kenyan strains ranged from 58% to 100% at the nucleotide level and 55% to 100% at the amino acid level. CONCLUSION: These results show that a wide range of HRV serotypes with different levels of nucleotide variation were present in Kenya. Furthermore, our data show that HRVs contributed substantially to influenza‐like illness in Kenya in 2008.",2016 May 2,"['Milanoi, Sylvia', 'Ongus, Juliette R.', 'Gachara, George', 'Coldren, Rodney', 'Bulimo, Wallace']",Influenza Other Respir Viruses,,,True
6312f554c8e95f9c8f3b5c0b150d88d35d657ae2,PMC,EV‐D68 infection in children with asthma exacerbation and pneumonia in Mexico City during 2014 autumn,http://dx.doi.org/10.1111/irv.12384,PMC4814865,26935868,CC BY,"BACKGROUND: Human enterovirus D68 (EV‐D68) recently caused an increase in mild‐to‐severe pediatric respiratory cases in North America and some European countries. Even though few of these children presented with acute paralytic disease, direct causal relationship cannot yet be assumed. OBJECTIVES: The purposes of this report were to describe the clinical findings of an outbreak of EV‐D68 infection in Mexico City and identify the genetic relationship with previously reported strains. PATIENTS/METHODS: Between September and December 2014, 126 nasopharyngeal samples (NPS) of hospitalized children <15 years of age with ARI were tested for the presence of respiratory viruses using a multiplex RT‐qPCR and EV‐D68‐specific RT‐qPCR. Clinical, epidemiological, and demographic data were collected and associated with symptomatology and viral infections. Phylogenetic analyses were performed using VP1 region. RESULTS: Enterovirus/rhinovirus infection was detected in 40 patients (31·7%), of which 24 patients were EV‐D68‐positive. EV‐D68 infection prevailed over September and October 2014 and was associated with neutrophilia and lymphopenia, and patients were more likely to develop hypoxemia. Phylogenetic analyses showed that Mexican EV‐D68 belongs to the new B1 clade. CONCLUSIONS: This is the first EV‐D68 outbreak described in Mexico and occurred few weeks after the United States reported similar infections. Although EV‐D68 belongs to new B1 clade, no neurological affection was observed.",2016 May 31,"['Vazquez‐Perez, Joel A.', 'Ramirez‐Gonzalez, Jose E.', 'Moreno‐Valencia, Yazmin', 'Hernandez‐Hernandez, Victor A.', 'Romero‐Espinoza, Jose A. I.', 'Castillejos‐Lopez, Manuel', 'Hernandez, Andres', 'Perez‐Padilla, Rogelio', 'Oropeza‐Lopez, Lizbeth E.', 'Escobar‐Escamilla, Noe', 'Gonzalez‐Villa, Maribel', 'Alejandre‐Garcia, Alejandro', 'Regalado‐Pineda, Justino', 'Santillan‐Doherty, Patricio', 'Lopez‐Martínez, Irma', 'Diaz‐Quiñonez, Alberto', 'Salas‐Hernandez, Jorge']",Influenza Other Respir Viruses,,,True
668aeb98c355caf8edcbbcb808215f26e7c388ad,PMC,Autophagy Negatively Regulates Transmissible Gastroenteritis Virus Replication,http://dx.doi.org/10.1038/srep23864,PMC4814908,27029407,CC BY,"Autophagy is an evolutionarily ancient pathway that has been shown to be important in the innate immune defense against several viruses. However, little is known about the regulatory role of autophagy in transmissible gastroenteritis virus (TGEV) replication. In this study, we found that TGEV infection increased the number of autophagosome-like double- and single-membrane vesicles in the cytoplasm of host cells, a phenomenon that is known to be related to autophagy. In addition, virus replication was required for the increased amount of the autophagosome marker protein LC3-II. Autophagic flux occurred in TGEV-infected cells, suggesting that TGEV infection triggered a complete autophagic response. When autophagy was pharmacologically inhibited by wortmannin or LY294002, TGEV replication increased. The increase in virus yield via autophagy inhibition was further confirmed by the use of siRNA duplexes, through which three proteins required for autophagy were depleted. Furthermore, TGEV replication was inhibited when autophagy was activated by rapamycin. The antiviral response of autophagy was confirmed by using siRNA to reduce the expression of gene p300, which otherwise inhibits autophagy. Together, the results indicate that TGEV infection activates autophagy and that autophagy then inhibits further TGEV replication.",2016 Mar 31,"['Guo, Longjun', 'Yu, Haidong', 'Gu, Weihong', 'Luo, Xiaolei', 'Li, Ren', 'Zhang, Jian', 'Xu, Yunfei', 'Yang, Lijun', 'Shen, Nan', 'Feng, Li', 'Wang, Yue']",Sci Rep,,,True
6bb3d6f24023746ace0ede108d88a4ed1f6e2e0d,PMC,Autophagy Negatively Regulates Transmissible Gastroenteritis Virus Replication,http://dx.doi.org/10.1038/srep23864,PMC4814908,27029407,CC BY,"Autophagy is an evolutionarily ancient pathway that has been shown to be important in the innate immune defense against several viruses. However, little is known about the regulatory role of autophagy in transmissible gastroenteritis virus (TGEV) replication. In this study, we found that TGEV infection increased the number of autophagosome-like double- and single-membrane vesicles in the cytoplasm of host cells, a phenomenon that is known to be related to autophagy. In addition, virus replication was required for the increased amount of the autophagosome marker protein LC3-II. Autophagic flux occurred in TGEV-infected cells, suggesting that TGEV infection triggered a complete autophagic response. When autophagy was pharmacologically inhibited by wortmannin or LY294002, TGEV replication increased. The increase in virus yield via autophagy inhibition was further confirmed by the use of siRNA duplexes, through which three proteins required for autophagy were depleted. Furthermore, TGEV replication was inhibited when autophagy was activated by rapamycin. The antiviral response of autophagy was confirmed by using siRNA to reduce the expression of gene p300, which otherwise inhibits autophagy. Together, the results indicate that TGEV infection activates autophagy and that autophagy then inhibits further TGEV replication.",2016 Mar 31,"['Guo, Longjun', 'Yu, Haidong', 'Gu, Weihong', 'Luo, Xiaolei', 'Li, Ren', 'Zhang, Jian', 'Xu, Yunfei', 'Yang, Lijun', 'Shen, Nan', 'Feng, Li', 'Wang, Yue']",Sci Rep,,,False
3f1a7bb419c2658dfd71663cc87efd03a38f1716,PMC,Quantitative Proteomic Analysis of Duck Ovarian Follicles Infected with Duck Tembusu Virus by Label-Free LC-MS,http://dx.doi.org/10.3389/fmicb.2016.00463,PMC4815560,27066001,CC BY,"Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has caused massive economic losses to the duck industry in China. DTMUV infection mainly results in significant decreases in egg production in egg-laying ducks within 1–2 weeks post infection. However, information on the comparative protein expression of host tissues in response to DTMUV infection is limited. In the present study, the cellular protein response to DTMUV infection in duck ovarian follicles was analyzed using nano-flow high-performance liquid chromatography-electrospray tandem mass spectrometry. Quantitative proteomic analysis revealed 131 differentially expressed proteins, among which 53 were up regulated and 78 were down regulated. The identified proteins were involved in the regulation of essential processes such as cellular structure and integrity, RNA processing, protein biosynthesis and modification, vesicle transport, signal transduction, and mitochondrial pathway. Some selected proteins that were found to be regulated in DTMUV-infected tissues were screened by quantitative real-time PCR to examine their regulation at the transcriptional level, western blot analysis was used to validate the changes of some selected proteins on translational level. To our knowledge, this study is the first to analyze the proteomic changes in duck ovarian follicles following DTMUV infection. The protein-related information obtained in this study may be useful to understand the host response to DTMUV infection and the inherent mechanism of DTMUV replication and pathogenicity.",2016 Mar 31,"['Han, Kaikai', 'Zhao, Dongmin', 'Liu, Yuzhuo', 'Liu, Qingtao', 'Huang, Xinmei', 'Yang, Jing', 'An, Fengjiao', 'Li, Yin']",Front Microbiol,,,True
33d46081e98cd5a3b1152ecee6361ae8f9f89ea9,PMC,Clinical Presentation and Birth Outcomes Associated with Respiratory Syncytial Virus Infection in Pregnancy,http://dx.doi.org/10.1371/journal.pone.0152015,PMC4816499,27031702,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is the most important cause of viral pneumonia in children worldwide. A maternal vaccine may protect both the mother and infant from RSV illness. The epidemiology and clinical presentation of RSV in pregnant and postpartum women is not well-described. METHODS: Data were collected from a prospective, randomized trial of influenza immunization in pregnant women in rural southern Nepal. Women were enrolled in their second trimester of pregnancy and followed until six months postpartum. Active weekly home-based surveillance for febrile respiratory illness was performed. Mid-nasal swabs collected with episodes of respiratory illness were tested for RSV by real-time polymerase chain reaction. RESULTS: RSV was detected in 14 (0.4%) illness episodes in 3693 women over 3554 person-years of surveillance from 2011–2014. RSV incidence was 3.9/1000 person-years overall, and 11.8/1000 person-years between September and December. Seven (50%) women sought care for RSV illness; none died. Of the 7 (50%) illness episodes during pregnancy, all had live births with 2 (29%) preterm births and a median birthweight of 3060 grams. This compares to 469 (13%) preterm births and a median birthweight of 2790 grams in women without RSV during pregnancy. Of the 7 mothers with postpartum RSV infection, RSV was detected in 4 (57%) of their infants. CONCLUSIONS: RSV was an uncommon cause of febrile respiratory illness in mothers during pregnancy in Nepal. These data will inform prevention and therapeutic strategies against RSV in resource-limited settings.",2016 Mar 31,"['Chu, Helen Y.', 'Katz, Joanne', 'Tielsch, James', 'Khatry, Subarna K.', 'Shrestha, Laxman', 'LeClerq, Steven C.', 'Magaret, Amalia', 'Kuypers, Jane', 'Steinhoff, Mark C.', 'Englund, Janet A.']",PLoS One,,,True
15753984412d073dd4c6daed84e3d294f728b636,PMC,Emergence of a Large-Plaque Variant in Mice Infected with Coxsackievirus B3,http://dx.doi.org/10.1128/mBio.00119-16,PMC4817249,27025249,CC BY,"Coxsackieviruses are enteric viruses that frequently infect humans. To examine coxsackievirus pathogenesis, we orally inoculated mice with the coxsackievirus B3 (CVB3) Nancy strain. Using HeLa cell plaque assays with agar overlays, we noticed that some fecal viruses generated plaques >100 times as large as inoculum viruses. These large-plaque variants emerged following viral replication in several different tissues. We identified a single amino acid change, N63Y, in the VP3 capsid protein that was sufficient to confer the large-plaque phenotype. Wild-type CVB3 and N63Y mutant CVB3 had similar plaque sizes when agarose was used in the overlay instead of agar. We determined that sulfated glycans in agar inhibited plaque formation by wild-type CVB3 but not by N63Y mutant CVB3. Furthermore, N63Y mutant CVB3 bound heparin, a sulfated glycan, less efficiently than wild-type CVB3 did. While N63Y mutant CVB3 had a growth defect in cultured cells and reduced attachment, it had enhanced replication and pathogenesis in mice. Infection with N63Y mutant CVB3 induced more severe hepatic damage than infection with wild-type CVB3, likely because N63Y mutant CVB3 disseminates more efficiently to the liver. Our data reinforce the idea that culture-adapted laboratory virus strains can have reduced fitness in vivo. N63Y mutant CVB3 may be useful as a platform to understand viral adaptation and pathogenesis in animal studies.",2016 Mar 29,"['Wang, Yao', 'Pfeiffer, Julie K.']",mBio,,,True
21d0dff90077800702fb5a6502246e9d512b6fe8,PMC,Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation,http://dx.doi.org/10.1128/mBio.00258-16,PMC4817253,27025250,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. Like many coronaviruses, MERS-CoV carries genes that encode multiple accessory proteins that are not required for replication of the genome but are likely involved in pathogenesis. Evasion of host innate immunity through interferon (IFN) antagonism is a critical component of viral pathogenesis. The IFN-inducible oligoadenylate synthetase (OAS)-RNase L pathway activates upon sensing of viral double-stranded RNA (dsRNA). Activated RNase L cleaves viral and host single-stranded RNA (ssRNA), which leads to translational arrest and subsequent cell death, preventing viral replication and spread. Here we report that MERS-CoV, a lineage C Betacoronavirus, and related bat CoV NS4b accessory proteins have phosphodiesterase (PDE) activity and antagonize OAS-RNase L by enzymatically degrading 2′,5′-oligoadenylate (2-5A), activators of RNase L. This is a novel function for NS4b, which has previously been reported to antagonize IFN signaling. NS4b proteins are distinct from lineage A Betacoronavirus PDEs and rotavirus gene-encoded PDEs, in having an amino-terminal nuclear localization signal (NLS) and are localized mostly to the nucleus. However, the expression level of cytoplasmic MERS-CoV NS4b protein is sufficient to prevent activation of RNase L. Finally, this is the first report of an RNase L antagonist expressed by a human or bat coronavirus and provides a specific mechanism by which this occurs. Our findings provide a potential mechanism for evasion of innate immunity by MERS-CoV while also identifying a potential target for therapeutic intervention.",2016 Mar 29,"['Thornbrough, Joshua M.', 'Jha, Babal K.', 'Yount, Boyd', 'Goldstein, Stephen A.', 'Li, Yize', 'Elliott, Ruth', 'Sims, Amy C.', 'Baric, Ralph S.', 'Silverman, Robert H.', 'Weiss, Susan R.']",mBio,,,True
a7b1bcb7b1806dce219451f289d56b14434f7ac1,PMC,S1 domain of the porcine epidemic diarrhea virus spike protein as a vaccine antigen,http://dx.doi.org/10.1186/s12985-016-0512-8,PMC4818391,27036203,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is a highly contagious virus infecting pigs of all ages with high morbidity and mortality among newborn piglets. Currently, there is no effective vaccine available to protect the pigs from PEDV. The N-terminal subunit of spike protein (S1) is responsible for virus binding to the cellular receptor and contains a number of neutralizing antibody epitopes. Thus, we expressed and produced recombinant S1 protein to protect newborn piglets by immunization of sows. METHODS: Affinity tagged PEDV S1 protein was expressed in a secretory form in yeast, insect and mammalian cells to identify the most suitable production system. Purified recombinant protein was analysed by SDS-PAGE, Western blot and deglycosylation assay. A pregnant sow was intramuscularly immunized three times with adjuvanted recombinant protein prior to farrowing. PEDV-specific immune responses in sera and colostrum of the sow and piglets were assayed by ELISA and virus neutralization assays. Piglets were challenged orally with PEDV, and clinical parameters were monitored for 6 days post-challenge. RESULTS AND CONCLUSION: Of three eukaryotic expression systems tested (yeast, insect-cell, and mammalian), expression by HEK-293 T cells gave the highest yield of protein that was N-glycosylated and was the most appropriate candidate for vaccination. Administration of the subunit vaccine in a sow resulted in induction of S1-specific IgG and IgA that were passively transferred to the suckling piglets. Also, high virus neutralization titres were observed in the serum of the vaccinated sow and its piglets. After PEDV challenge, piglets born to the vaccinated sow exhibited less severe signs of disease and significantly lower mortality compared to the piglets of a control sow. However, there were no significant differences in diarrhea, body weight and virus shedding. Thus, vaccination with S1 subunit vaccine failed to provide complete protection to suckling piglets after challenge exposure, and further improvements are needed for the development of a subunit vaccine that fully protects against PEDV infection.",2016 Apr 1,"['Makadiya, Niraj', 'Brownlie, Robert', 'van den Hurk, Jan', 'Berube, Nathalie', 'Allan, Brenda', 'Gerdts, Volker', 'Zakhartchouk, Alexander']",Virol J,,,True
34081c03e48678c7d7633e81cecdeb0b6dbf30e4,PMC,Nottingham Trent University and Makerere University School of Public Health partnership: experiences of co-learning and supporting the healthcare system in Uganda,http://dx.doi.org/10.1186/s12992-016-0148-x,PMC4818423,27036632,CC BY,"Partnerships between developed and developing country institutions are increasingly becoming important in addressing contemporary global health challenges faced by health systems. Inter-university health collaboration such as the Nottingham Trent University (UK) and Makerere University School of Public Health (Uganda) partnership provide opportunities for working together in training, research and service delivery while strengthening health systems. This paper shares the experiences, achievements and opportunities of this partnership in co-learning and supporting the health system in Uganda. This includes a project being implemented to strengthen the training, supervision and motivation of community health workers in rural Uganda. Training and research are a key focus of the partnership and have involved both staff and students of both institutions including guest lectures, seminars and conference presentations. The partnership’s collaboration with stakeholders such as the Ministry of Health (Uganda) and local health authorities has ensured participation necessary in supporting implementation of sustainable interventions. The partnership uses several channels such as email, telephone, Skype, Dropbox and WhatsApp which have been useful in maintaining constant and effective communication. The challenges faced by the partnership include lack of funding to support student mobility, and varying academic schedules of the two institutions. The experiences and prospects of this growing partnership can inform other collaborations in similar settings.",2016 Mar 28,"['Musoke, David', 'Gibson, Linda', 'Mukama, Trasias', 'Khalil, Yesmean', 'Ssempebwa, John C.']",Global Health,,,True
95af044a0d57fffb101b547ff1f58122d05771bb,PMC,Protecting health workers from infectious disease transmission: an exploration of a Canadian-South African partnership of partnerships,http://dx.doi.org/10.1186/s12992-016-0145-0,PMC4818531,27036516,CC BY,"BACKGROUND: Health workers are at high risk of acquiring infectious diseases at work, especially in low and middle-income countries (LMIC) with critical health human resource deficiencies and limited implementation of occupational health and infection control measures. Amidst increasing interest in international partnerships to address such issues, how best to develop such collaborations is being actively debated. In 2006, a partnership developed between occupational health and infection control experts in Canada and institutions in South Africa (including an institute with a national mandate to conduct research and provide guidance to protect health workers from infectious diseases and promote improved working conditions). This article describes the collaboration, analyzes the determinants of success and shares lessons learned. METHODS: Synthesizing participant-observer experience from over 9 years of collaboration and 10 studies already published from this work, we applied a realist review analysis to describe the various achievements at global, national, provincial and hospital levels. Expectations of the various parties on developing new insights, providing training, and addressing service needs were examined through a micro-meso-macro lens, focusing on how each main partner organization contributed to and benefitted from working together. RESULTS: A state-of-the-art occupational health and safety surveillance program was established in South Africa following successful technology transfer from a similar undertaking in Canada and training was conducted that synergistically benefitted Northern as well as Southern trainees. Integrated policies combining infection control and occupational health to prevent and control infectious disease transmission among health workers were also launched. Having a national (South-South) network reinforced by the international (North–south) partnership was pivotal in mitigating the challenges that emerged. CONCLUSIONS: High-income country partnerships with experience in health system strengthening – particularly in much needed areas such as occupational health and infection control – can effectively work through strong collaborators in the Global South to build capacity. Partnerships are particularly well positioned to sustainably reinforce efforts at national and sub-national LMIC levels when they adopt a “communities of practice” model, characterized by multi-directional learning. The principles of effective collaboration learned in this “partnership of partnerships” to improve working conditions for health workers can be applied to other areas where health system strengthening is needed.",2016 Mar 31,"['Yassi, Annalee', 'Zungu, Muzimkhulu', 'Spiegel, Jerry M.', 'Kistnasamy, Barry', 'Lockhart, Karen', 'Jones, David', 'O’Hara, Lyndsay M.', 'Nophale, Letshego', 'Bryce, Elizabeth A.', 'Darwin, Lincoln']",Global Health,,,True
3656fed9d1f687fd87440d7da4f3d852aa1dcdc4,PMC,Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis,http://dx.doi.org/10.15252/emmm.201505986,PMC4818751,26992832,CC BY,"Currently available rabies post‐exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad‐spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non‐RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post‐vaccination antibody response.",2016 Apr 18,"['De Benedictis, Paola', 'Minola, Andrea', 'Rota Nodari, Elena', 'Aiello, Roberta', 'Zecchin, Barbara', 'Salomoni, Angela', 'Foglierini, Mathilde', 'Agatic, Gloria', 'Vanzetta, Fabrizia', 'Lavenir, Rachel', 'Lepelletier, Anthony', 'Bentley, Emma', 'Weiss, Robin', 'Cattoli, Giovanni', 'Capua, Ilaria', 'Sallusto, Federica', 'Wright, Edward', 'Lanzavecchia, Antonio', 'Bourhy, Hervé', 'Corti, Davide']",EMBO Mol Med,,,True
f0dfa7ee5ac42ad3ab47c11f776fd5571b3b4fc1,PMC,Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis,http://dx.doi.org/10.15252/emmm.201505986,PMC4818751,26992832,CC BY,"Currently available rabies post‐exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad‐spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non‐RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post‐vaccination antibody response.",2016 Apr 18,"['De Benedictis, Paola', 'Minola, Andrea', 'Rota Nodari, Elena', 'Aiello, Roberta', 'Zecchin, Barbara', 'Salomoni, Angela', 'Foglierini, Mathilde', 'Agatic, Gloria', 'Vanzetta, Fabrizia', 'Lavenir, Rachel', 'Lepelletier, Anthony', 'Bentley, Emma', 'Weiss, Robin', 'Cattoli, Giovanni', 'Capua, Ilaria', 'Sallusto, Federica', 'Wright, Edward', 'Lanzavecchia, Antonio', 'Bourhy, Hervé', 'Corti, Davide']",EMBO Mol Med,,,False
b47215082b8b863141fa268157d54a1ea6c067eb,PMC,Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis,http://dx.doi.org/10.15252/emmm.201505986,PMC4818751,26992832,CC BY,"Currently available rabies post‐exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad‐spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non‐RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post‐vaccination antibody response.",2016 Apr 18,"['De Benedictis, Paola', 'Minola, Andrea', 'Rota Nodari, Elena', 'Aiello, Roberta', 'Zecchin, Barbara', 'Salomoni, Angela', 'Foglierini, Mathilde', 'Agatic, Gloria', 'Vanzetta, Fabrizia', 'Lavenir, Rachel', 'Lepelletier, Anthony', 'Bentley, Emma', 'Weiss, Robin', 'Cattoli, Giovanni', 'Capua, Ilaria', 'Sallusto, Federica', 'Wright, Edward', 'Lanzavecchia, Antonio', 'Bourhy, Hervé', 'Corti, Davide']",EMBO Mol Med,,,False
e793ed5d6d883cd196795a4ca5d1ae0fbe632b34,PMC,Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis,http://dx.doi.org/10.15252/emmm.201505986,PMC4818751,26992832,CC BY,"Currently available rabies post‐exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad‐spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non‐RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post‐vaccination antibody response.",2016 Apr 18,"['De Benedictis, Paola', 'Minola, Andrea', 'Rota Nodari, Elena', 'Aiello, Roberta', 'Zecchin, Barbara', 'Salomoni, Angela', 'Foglierini, Mathilde', 'Agatic, Gloria', 'Vanzetta, Fabrizia', 'Lavenir, Rachel', 'Lepelletier, Anthony', 'Bentley, Emma', 'Weiss, Robin', 'Cattoli, Giovanni', 'Capua, Ilaria', 'Sallusto, Federica', 'Wright, Edward', 'Lanzavecchia, Antonio', 'Bourhy, Hervé', 'Corti, Davide']",EMBO Mol Med,,,True
5864eb909b8a0b74359b9d4ae2ace23e41287159,PMC,Chances and challenges in China,http://dx.doi.org/10.1007/s13238-015-0235-4,PMC4818847,26687390,CC BY,,2016 Apr 19,"Tefsen, Boris",Protein Cell,,,True
586df9c5c975c38a6f646674374a1eb98d280f62,PMC,Small Non-coding RNAs Associated with Viral Infectious Diseases of Veterinary Importance: Potential Clinical Applications,http://dx.doi.org/10.3389/fvets.2016.00022,PMC4819147,27092305,CC BY,"MicroRNAs (miRNAs) represent a class of small non-coding RNA (sncRNA) molecules that can regulate mRNAs by inducing their degradation or by blocking translation. Considering that miRNAs are ubiquitous, stable, and conserved across animal species, it seems feasible to exploit them for clinical applications. Unlike in human viral diseases, where some miRNA-based molecules have progressed to clinical application, in veterinary medicine, this concept is just starting to come into view. Clinically, miRNAs could represent powerful diagnostic tools to pinpoint animal viral diseases and/or prognostic tools to follow up disease progression or remission. Additionally, the possible consequences of miRNA dysregulation make them potential therapeutic targets and open the possibilities to use them as tools to generate viral disease-resistant livestock. This review presents an update of preclinical studies on using sncRNAs to combat viral diseases that affect pet and farm animals. Moreover, we discuss the possibilities and challenges of bringing these bench-based discoveries to the veterinary clinic.",2016 Apr 4,"['Samir, Mohamed', 'Pessler, Frank']",Front Vet Sci,,,True
f6d1e68561dad02f11de4b9882893826bb6321a4,PMC,Harm reduction policy in Taiwan: toward a comprehensive understanding of its making and effects,http://dx.doi.org/10.1186/s12954-016-0101-6,PMC4819272,27044357,CC BY,"BACKGROUND: In response to the spread of HIV caused by needle sharing among injection drug users (IDUs), the Taiwan Centers for Disease Control implemented a pilot harm reduction program in 2005 that expanded nationwide in 2006. The policy led to a significant reduction in the number of HIV-positive cases among IDUs in 4 years. METHODS: This article aims to provide a critical evaluation of this harm reduction policy in Taiwan. The research leading to this article included a thorough literature review and in-depth interviews with 31 active policy participants, including people working in hospitals, the academia, non-governmental organizations, community pharmacies, the legal system, and health authorities at both the central and local levels. The collected data were analyzed on the basis of situational analysis. RESULTS: The article examines the policy success by showing how this policy was assembled and by exposing the frictions and adjustments during its formation and implementation. Inter-departmental conflicts within or without the government and the efforts to coordinate them are addressed, and the transnational dimensions of this harm reduction policy are also discussed. The article then reflects on the effects of the policy and asks where the line should be drawn between what is harm reduction and what is not. CONCLUSIONS: This case illustration reveals the complexity of understanding an assembled health policy that involves multiple participants. The article intends to render an analytic account to enable a comparison with similar policies in other countries.",2016 Apr 4,"Chen, Jia-shin",Harm Reduct J,,,True
7b5111143804a15cd9120956dd6f29e4e1dcc439,PMC,Detection of Clostridium perfringens alpha toxin gene in lambs by loop mediated isothermal amplification,http://dx.doi.org/10.14202/vetworld.2016.60-64,PMC4819352,27051186,CC BY,"AIM: The loop mediated isothermal amplification (LAMP) was standardized for rapid detection of Clostridium perfringens. MATERIALS AND METHODS: A total of 120 fecal samples were collected from enterotoxemia suspected lambs were used for screening of C. perfringens cpa gene by LAMP. The specificity of the LAMP amplified products was tested by digesting with restriction enzyme XmnI for alpha toxin gene. RESULTS: Out of 120 samples screened 112 (93.3%) samples were positive by both LAMP and polymerase chain reaction (PCR) for detection of cpa gene which indicated the equal sensitivity of both the tests. The enzyme produced single cut in 162 base pair amplified product of alpha toxin gene at 81 base pair resulting in a single band in gel electrophoresis. CONCLUSION: Both LAMP and PCR for detection of cpa gene indicated the equal sensitivity of both the tests. Standardization of LAMP reaction for amplification of epsilon and beta toxin genes will help to identify the C. perfringens toxin types from the clinical samples. The test could be a suitable alternative to the PCR in detection of toxin types without the help of sophisticated machinery like thermal cycler. Considering its simplicity in operation and high sensitivity, there is the potential use of this technique in clinical diagnosis and surveillance of infectious diseases.",2016 Jan 20,"['Radhika, B.', 'Kumar, N. Vinod', 'Sreenivasulu, D.']",Vet World,,,True
2ec6d0d83b08c9b4e1784e319978aff1930d5484,PMC,What Effect Did the Global Financial Crisis Have Upon Youth Wellbeing? Evidence From Four Australian Cohorts,http://dx.doi.org/10.1037/dev0000092,PMC4819495,26854968,CC BY,"Recent research has suggested significant negative effects of the Global Financial Crisis (GFC) on mental health and wellbeing. In this article, the authors suggest that the developmental period of late adolescence may be at particular risk of economic downturns. Harmonizing 4 longitudinal cohorts of Australian youth (N = 38,017), we estimate the impact of the GFC on 1 general and 11 domain specific measures of wellbeing at age 19 and 22. Significant differences in wellbeing in most life domains were found, suggesting that wellbeing is susceptible to economic shocks. Given that the GFC in Australia was relatively mild, the finding of clear negative effects across 2 ages is of international concern.",2016 Apr 8,"['Parker, Philip D.', 'Jerrim, John', 'Anders, Jake']",Dev Psychol,,,True
d4f1ccfcf8b71a2828f39991e67142dd3a57fd1a,PMC,Comparative genomic analysis of pre-epidemic and epidemic Zika virus strains for virological factors potentially associated with the rapidly expanding epidemic,http://dx.doi.org/10.1038/emi.2016.48,PMC4820678,26980239,CC BY,"Less than 20 sporadic cases of human Zika virus (ZIKV) infection were reported in Africa and Asia before 2007, but large outbreaks involving up to 73% of the populations on the Pacific islands have started since 2007, and spread to the Americas in 2014. Moreover, the clinical manifestation of ZIKV infection has apparently changed, as evident by increasing reports of neurological complications, such as Guillain–Barré syndrome in adults and congenital anomalies in neonates. We comprehensively compared the genome sequences of pre-epidemic and epidemic ZIKV strains with complete genome or complete polyprotein sequences available in GenBank. Besides the reported phylogenetic clustering of the epidemic strains with the Asian lineage, we found that the topology of phylogenetic tree of all coding regions is the same except that of the non-structural 2B (NS2B) coding region. This finding was confirmed by bootscan analysis and multiple sequence alignment, which suggested the presence of a fragment of genetic recombination at NS2B with that of Spondweni virus. Moreover, the representative epidemic strain possesses one large bulge of nine bases instead of an external loop on the first stem-loop structure at the 3′-untranslated region just distal to the stop codon of the NS5 in the 1947 pre-epidemic prototype strain. Fifteen amino acid substitutions are found in the epidemic strains when compared with the pre-epidemic strains. As mutations in other flaviviruses can be associated with changes in virulence, replication efficiency, antigenic epitopes and host tropism, further studies would be important to ascertain the biological significance of these genomic changes.",2016 Mar 16,"['Zhu, Zheng', 'Chan, Jasper Fuk-Woo', 'Tee, Kah-Meng', 'Choi, Garnet Kwan-Yue', 'Lau, Susanna Kar-Pui', 'Woo, Patrick Chiu-Yat', 'Tse, Herman', 'Yuen, Kwok-Yung']",Emerg Microbes Infect,,,True
c798225c8b1b45e38fcd6163a711500c1f667b03,PMC,Combined approaches of EPR and NMR illustrate only one transmembrane helix in the human IFITM3,http://dx.doi.org/10.1038/srep24029,PMC4820770,27046158,CC BY,"Interferon-inducible transmembrane protein IFITM3 was known to restrict the entry of a wide spectrum of viruses to the cytosol of the host. The mechanism used by the protein to restrict viral entry is unclear given the unavailability of the membrane topology and structures of the IFITM family proteins. Systematic site-directed spin labeling (SDSL) and electron paramagnetic resonance (EPR) studies of IFITM3 in detergent micelles identified a single, long transmembrane helix in the C-terminus and an intramembrane segment in the N-terminal hydrophobic region. Solution NMR studies of the same sample verified the secondary structure distribution and demonstrated two rigid regions interacting with the micellar surface. The resulting membrane topology of IFITM3 supports the mechanism of an enhanced restricted membrane hemi-fusion.",2016 Apr 5,"['Ling, Shenglong', 'Zhang, Chengwei', 'Wang, Wei', 'Cai, Xiaoying', 'Yu, Lu', 'Wu, Fangming', 'Zhang, Longhua', 'Tian, Changlin']",Sci Rep,,,True
5846be53e7718e1a6ffae34ed5136693fd462bd8,PMC,Combined approaches of EPR and NMR illustrate only one transmembrane helix in the human IFITM3,http://dx.doi.org/10.1038/srep24029,PMC4820770,27046158,CC BY,"Interferon-inducible transmembrane protein IFITM3 was known to restrict the entry of a wide spectrum of viruses to the cytosol of the host. The mechanism used by the protein to restrict viral entry is unclear given the unavailability of the membrane topology and structures of the IFITM family proteins. Systematic site-directed spin labeling (SDSL) and electron paramagnetic resonance (EPR) studies of IFITM3 in detergent micelles identified a single, long transmembrane helix in the C-terminus and an intramembrane segment in the N-terminal hydrophobic region. Solution NMR studies of the same sample verified the secondary structure distribution and demonstrated two rigid regions interacting with the micellar surface. The resulting membrane topology of IFITM3 supports the mechanism of an enhanced restricted membrane hemi-fusion.",2016 Apr 5,"['Ling, Shenglong', 'Zhang, Chengwei', 'Wang, Wei', 'Cai, Xiaoying', 'Yu, Lu', 'Wu, Fangming', 'Zhang, Longhua', 'Tian, Changlin']",Sci Rep,,,False
de2da69b84bad743d1e16d52a12d4ea8ca9f66d9,PMC,Evaluation of serological cross-reactivity and cross-neutralization between the United States porcine epidemic diarrhea virus prototype and S-INDEL-variant strains,http://dx.doi.org/10.1186/s12917-016-0697-5,PMC4820917,27044253,CC BY,"BACKGROUND: At least two genetically different porcine epidemic diarrhea virus (PEDV) strains have been identified in the United States (U.S. PEDV prototype and S-INDEL-variant strains). The current serological assays offered at veterinary diagnostic laboratories for detection of PEDV-specific antibody are based on the U.S. PEDV prototype strain. The objectives of this study were: 1) isolate the U.S. PEDV S-INDEL-variant strain in cell culture; 2) generate antisera against the U.S. PEDV prototype and S-INDEL-variant strains by experimentally infecting weaned pigs; 3) determine if the various PEDV serological assays could detect antibodies against the U.S. PEDV S-INDEL-variant strain and vice versa. RESULTS: A U.S. PEDV S-INDEL-variant strain was isolated in cell culture in this study. Three groups of PEDV-negative, 3-week-old pigs (five pigs per group) were inoculated orally with a U.S. PEDV prototype isolate (previously isolated in our lab), an S-INDEL-variant isolate or virus-negative culture medium. Serum samples collected at 0, 7, 14, 21 and 28 days post inoculation were evaluated by the following PEDV serological assays: 1) indirect fluorescent antibody (IFA) assays using the prototype and S-INDEL-variant strains as indicator viruses; 2) virus neutralization (VN) tests against the prototype and S-INDEL-variant viruses; 3) PEDV prototype strain whole virus based ELISA; 4) PEDV prototype strain S1-based ELISA; and 5) PEDV S-INDEL-variant strain S1-based ELISA. The positive antisera against the prototype strain reacted to and neutralized both prototype and S-INDEL-variant viruses, and the positive antisera against the S-INDEL-variant strain also reacted to and neutralized both prototype and S-INDEL-variant viruses, as examined by IFA antibody assays and VN tests. Antibodies against the two PEDV strains could be detected by all three ELISAs although detection rates varied to some degree. CONCLUSIONS: These data indicate that the antibodies against U.S. PEDV prototype and S-INDEL-variant strains cross-reacted and cross-neutralized both strains in vitro. The current serological assays based on U.S. PEDV prototype strain can detect antibodies against both U.S. PEDV strains.",2016 Apr 5,"['Chen, Qi', 'Thomas, Joseph T.', 'Giménez-Lirola, Luis G.', 'Hardham, John M.', 'Gao, Qinshan', 'Gerber, Priscilla F.', 'Opriessnig, Tanja', 'Zheng, Ying', 'Li, Ganwu', 'Gauger, Phillip C.', 'Madson, Darin M.', 'Magstadt, Drew R.', 'Zhang, Jianqiang']",BMC Vet Res,,,True
1d613eb26d86e376a5f8cb5fdb673b7254110936,PMC,Bayesian Monitoring of Emerging Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0152629,PMC4821533,27045370,CC BY,"We define data analyses to monitor a change in R, the average number of secondary cases caused by a typical infected individual. The input dataset consists of incident cases partitioned into outbreaks, each initiated from a single index case. We split the input dataset into two successive subsets, to evaluate two successive R values, according to the Bayesian paradigm. We used the Bayes factor between the model with two different R values and that with a single R value to justify that the change in R is statistically significant. We validated our approach using simulated data, generated using known R. In particular, we found that claiming two distinct R values may depend significantly on the number of outbreaks. We then reanalyzed data previously studied by Jansen et al. [Jansen et al. Science 301 (5634), 804], concerning the effective reproduction number for measles in the UK, during 1995–2002. Our analyses showed that the 1995–2002 dataset should be divided into two separate subsets for the periods 1995–1998 and 1999–2002. In contrast, Jansen et al. take this splitting point as input of their analysis. Our estimated effective reproduction numbers R are in good agreement with those found by Jansen et al. In conclusion, our methodology for detecting temporal changes in R using outbreak-size data worked satisfactorily with both simulated and real-world data. The methodology may be used for updating R in real time, as surveillance outbreak data become available.",2016 Apr 5,"['Polyakov, Pavel', 'Breban, Romulus']",PLoS One,,,True
567942b67459da90977129ef385ef9f6a2133abb,PMC,The new (dis)order in RNA regulation,http://dx.doi.org/10.1186/s12964-016-0132-3,PMC4822317,27048167,CC BY,"RNA-binding proteins play a key role in the regulation of all aspects of RNA metabolism, from the synthesis of RNA to its decay. Protein-RNA interactions have been thought to be mostly mediated by canonical RNA-binding domains that form stable secondary and tertiary structures. However, a number of pioneering studies over the past decades, together with recent proteome-wide data, have challenged this view, revealing surprising roles for intrinsically disordered protein regions in RNA binding. Here, we discuss how disordered protein regions can mediate protein-RNA interactions, conceptually grouping these regions into RS-rich, RG-rich, and other basic sequences, that can mediate both specific and non-specific interactions with RNA. Disordered regions can also influence RNA metabolism through protein aggregation and hydrogel formation. Importantly, protein-RNA interactions mediated by disordered regions can influence nearly all aspects of co- and post-transcriptional RNA processes and, consequently, their disruption can cause disease. Despite growing interest in disordered protein regions and their roles in RNA biology, their mechanisms of binding, regulation, and physiological consequences remain poorly understood. In the coming years, the study of these unorthodox interactions will yield important insights into RNA regulation in cellular homeostasis and disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12964-016-0132-3) contains supplementary material, which is available to authorized users.",2016 Apr 6,"['Järvelin, Aino I.', 'Noerenberg, Marko', 'Davis, Ilan', 'Castello, Alfredo']",Cell Commun Signal,,,False
532f2c636fca1caae1f23885b9dc0e3302a0afd5,PMC,The new (dis)order in RNA regulation,http://dx.doi.org/10.1186/s12964-016-0132-3,PMC4822317,27048167,CC BY,"RNA-binding proteins play a key role in the regulation of all aspects of RNA metabolism, from the synthesis of RNA to its decay. Protein-RNA interactions have been thought to be mostly mediated by canonical RNA-binding domains that form stable secondary and tertiary structures. However, a number of pioneering studies over the past decades, together with recent proteome-wide data, have challenged this view, revealing surprising roles for intrinsically disordered protein regions in RNA binding. Here, we discuss how disordered protein regions can mediate protein-RNA interactions, conceptually grouping these regions into RS-rich, RG-rich, and other basic sequences, that can mediate both specific and non-specific interactions with RNA. Disordered regions can also influence RNA metabolism through protein aggregation and hydrogel formation. Importantly, protein-RNA interactions mediated by disordered regions can influence nearly all aspects of co- and post-transcriptional RNA processes and, consequently, their disruption can cause disease. Despite growing interest in disordered protein regions and their roles in RNA biology, their mechanisms of binding, regulation, and physiological consequences remain poorly understood. In the coming years, the study of these unorthodox interactions will yield important insights into RNA regulation in cellular homeostasis and disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12964-016-0132-3) contains supplementary material, which is available to authorized users.",2016 Apr 6,"['Järvelin, Aino I.', 'Noerenberg, Marko', 'Davis, Ilan', 'Castello, Alfredo']",Cell Commun Signal,,,True
ad4dc41b48d9f6024088cb6c65a51972d928d200,PMC,Predicting and Evaluating the Epidemic Trend of Ebola Virus Disease in the 2014-2015 Outbreak and the Effects of Intervention Measures,http://dx.doi.org/10.1371/journal.pone.0152438,PMC4822846,27049322,CC BY,"We constructed dynamic Ebola virus disease (EVD) transmission models to predict epidemic trends and evaluate intervention measure efficacy following the 2014 EVD epidemic in West Africa. We estimated the effective vaccination rate for the population, with basic reproduction number (R(0)) as the intermediate variable. Periodic EVD fluctuation was analyzed by solving a Jacobian matrix of differential equations based on a SIR (susceptible, infective, and removed) model. A comprehensive compartment model was constructed to fit and predict EVD transmission patterns, and to evaluate the effects of control and prevention measures. Effective EVD vaccination rates were estimated to be 42% (31–50%), 45% (42–48%), and 51% (44–56%) among susceptible individuals in Guinea, Liberia and Sierra Leone, respectively. In the absence of control measures, there would be rapid mortality in these three countries, and an EVD epidemic would be likely recur in 2035, and then again 8~9 years later. Oscillation intervals would shorten and outbreak severity would decrease until the periodicity reached ~5.3 years. Measures that reduced the spread of EVD included: early diagnosis, treatment in isolation, isolating/monitoring close contacts, timely corpse removal, post-recovery condom use, and preventing or quarantining imported cases. EVD may re-emerge within two decades without control and prevention measures. Mass vaccination campaigns and control and prevention measures should be instituted to prevent future EVD epidemics.",2016 Apr 6,"['Guo, Zuiyuan', 'Xiao, Dan', 'Li, Dongli', 'Wang, Xiuhong', 'Wang, Yayu', 'Yan, Tiecheng', 'Wang, Zhiqi']",PLoS One,,,True
996fc493a4d72390383d242d35515dc8144bb36d,PMC,Does Circulating Antibody Play a Role in the Protection of Piglets against Porcine Epidemic Diarrhea Virus?,http://dx.doi.org/10.1371/journal.pone.0153041,PMC4822964,27050556,CC BY,"The contribution of circulating antibody to the protection of naïve piglets against porcine epidemic diarrhea virus (PEDV) was evaluated using a passive antibody transfer model. Piglets (n = 62) derived from 6 sows were assigned to one of 6 different treatments using a randomized block design which provided for allocation of all treatments to all sows' litters. Each treatment was designed to achieve a different level of circulating anti-PEDV antibody via intraperitoneally administration of concentrated serum antibody. Piglets were orally inoculated with PEDV (USA/IN/2013/19338E, 1 x 10(3) TCID(50) per piglet) 24 hours later and then monitored for 14 days. Piglets remained with their dam throughout the experiment. Sow milk samples, piglet fecal samples, and data on piglet clinical signs, body weight, and body temperature were collected daily. Fecal samples were tested by PEDV real-time reverse transcriptase PCR. Serum, colostrum, and milk were tested for PEDV IgG, IgA, and virus-neutralizing antibody. The data were evaluated for the effects of systemic PEDV antibody levels on growth, body temperature, fecal shedding, survival, and antibody response. The analysis showed that circulating antibody partially ameliorated the effect of PEDV infection. Specifically, antibody-positive groups returned to normal body temperature faster and demonstrated a higher rate of survivability than piglets without PEDV antibody. When combined with previous literature on PEDV, it can be concluded that both systemic antibodies and maternal secretory IgA in milk contribute to the protection of the neonatal pig against PEDV infections. Overall, the results of this experiment suggested that passively administered circulating antibodies contributed to the protection of neonatal piglets against PEDV infection.",2016 Apr 6,"['Poonsuk, Korakrit', 'Giménez-Lirola, Luis Gabriel', 'Zhang, Jianqiang', 'Arruda, Paolo', 'Chen, Qi', 'Correa da Silva Carrion, Lucas', 'Magtoto, Ronaldo', 'Pineyro, Pablo', 'Sarmento, Luciana', 'Wang, Chong', 'Sun, Yaxuan', 'Madson, Darin', 'Johnson, John', 'Yoon, Kyoung-Jin', 'Zimmerman, Jeffrey', 'Main, Rodger']",PLoS One,,,True
e87dc948912d7ec9174234037dec7c4369c5360c,PMC,Preparedness of healthcare workers at French Ebola referral centres,http://dx.doi.org/10.1016/j.nmni.2014.12.005,PMC4823472,27096101,CC BY,,2015 Feb 17,"['Tarantini, C.', 'Peretti-Watel, P.', 'Yazdanpana, Y.', 'Guery, B.', 'Chidiac, C.', 'Rapp, C.', 'Brouqui, P.']",New Microbes New Infect,,,False
105268027d44ab275991e358674462f77223e882,PMC,Complete Genome Sequence of the Porcine Epidemic Diarrhea Virus Strain SLO/JH-11/2015,http://dx.doi.org/10.1128/genomeA.01725-15,PMC4824273,27056240,CC BY,"Porcine epidemic diarrhea virus (PEDV) was detected for the first time in Slovenia in January 2015. The complete genome sequence of PEDV strain SLO/JH-11/2015, obtained from a fecal sample of a fattening pig with diarrhea in September 2015, is closely related to recently detected European strains.",2016 Apr 7,"['Toplak, Ivan', 'Ipavec, Manica', 'Kuhar, Urška', 'Kušar, Darja', 'Papić, Bojan', 'Koren, Simon', 'Toplak, Nataša']",Genome Announc,,,True
5d3e915d8571f298da4ff2e929d8475d68dc559f,PMC,Viruses Utilize Cellular Cues in Distinct Combination to Undergo Systematic Priming and Uncoating,http://dx.doi.org/10.1371/journal.ppat.1005467,PMC4824415,27055025,CC BY,,2016 Apr 7,"['Ravindran, Madhu Sudhan', 'Tsai, Billy']",PLoS Pathog,,,True
d0620683a194e739baca5c13917899ad7e5b2337,PMC,VIP: an integrated pipeline for metagenomics of virus identification and discovery,http://dx.doi.org/10.1038/srep23774,PMC4824449,27026381,CC BY,"Identification and discovery of viruses using next-generation sequencing technology is a fast-developing area with potential wide application in clinical diagnostics, public health monitoring and novel virus discovery. However, tremendous sequence data from NGS study has posed great challenge both in accuracy and velocity for application of NGS study. Here we describe VIP (“Virus Identification Pipeline”), a one-touch computational pipeline for virus identification and discovery from metagenomic NGS data. VIP performs the following steps to achieve its goal: (i) map and filter out background-related reads, (ii) extensive classification of reads on the basis of nucleotide and remote amino acid homology, (iii) multiple k-mer based de novo assembly and phylogenetic analysis to provide evolutionary insight. We validated the feasibility and veracity of this pipeline with sequencing results of various types of clinical samples and public datasets. VIP has also contributed to timely virus diagnosis (~10 min) in acutely ill patients, demonstrating its potential in the performance of unbiased NGS-based clinical studies with demand of short turnaround time. VIP is released under GPLv3 and is available for free download at: https://github.com/keylabivdc/VIP.",2016 Mar 30,"['Li, Yang', 'Wang, Hao', 'Nie, Kai', 'Zhang, Chen', 'Zhang, Yi', 'Wang, Ji', 'Niu, Peihua', 'Ma, Xuejun']",Sci Rep,,,True
aeba70238bd0c68d3995b9a241da7cb9d2bf73dc,PMC,VIP: an integrated pipeline for metagenomics of virus identification and discovery,http://dx.doi.org/10.1038/srep23774,PMC4824449,27026381,CC BY,"Identification and discovery of viruses using next-generation sequencing technology is a fast-developing area with potential wide application in clinical diagnostics, public health monitoring and novel virus discovery. However, tremendous sequence data from NGS study has posed great challenge both in accuracy and velocity for application of NGS study. Here we describe VIP (“Virus Identification Pipeline”), a one-touch computational pipeline for virus identification and discovery from metagenomic NGS data. VIP performs the following steps to achieve its goal: (i) map and filter out background-related reads, (ii) extensive classification of reads on the basis of nucleotide and remote amino acid homology, (iii) multiple k-mer based de novo assembly and phylogenetic analysis to provide evolutionary insight. We validated the feasibility and veracity of this pipeline with sequencing results of various types of clinical samples and public datasets. VIP has also contributed to timely virus diagnosis (~10 min) in acutely ill patients, demonstrating its potential in the performance of unbiased NGS-based clinical studies with demand of short turnaround time. VIP is released under GPLv3 and is available for free download at: https://github.com/keylabivdc/VIP.",2016 Mar 30,"['Li, Yang', 'Wang, Hao', 'Nie, Kai', 'Zhang, Chen', 'Zhang, Yi', 'Wang, Ji', 'Niu, Peihua', 'Ma, Xuejun']",Sci Rep,,,True
f6d409a4fff5c3c4d7d84cee872e80615e2027a4,PMC,Estimating risks of importation and local transmission of Zika virus infection,http://dx.doi.org/10.7717/peerj.1904,PMC4824915,27069825,CC BY,"Background. An international spread of Zika virus (ZIKV) infection has attracted global attention. ZIKV is conveyed by a mosquito vector, Aedes species, which also acts as the vector species of dengue and chikungunya viruses. Methods. Arrival time of ZIKV importation (i.e., the time at which the first imported case was diagnosed) in each imported country was collected from publicly available data sources. Employing a survival analysis model in which the hazard is an inverse function of the effective distance as informed by the airline transportation network data, and using dengue and chikungunya virus transmission data, risks of importation and local transmission were estimated. Results. A total of 78 countries with imported case(s) have been identified, with the arrival time ranging from 1 to 44 weeks since the first ZIKV was identified in Brazil, 2015. Whereas the risk of importation was well explained by the airline transportation network data, the risk of local transmission appeared to be best captured by additionally accounting for the presence of dengue and chikungunya viruses. Discussion. The risk of importation may be high given continued global travel of mildly infected travelers but, considering that the public health concerns over ZIKV infection stems from microcephaly, it is more important to focus on the risk of local and widespread transmission that could involve pregnant women. The predicted risk of local transmission was frequently seen in tropical and subtropical countries with dengue or chikungunya epidemic experience.",2016 Apr 5,"['Nah, Kyeongah', 'Mizumoto, Kenji', 'Miyamatsu, Yuichiro', 'Yasuda, Yohei', 'Kinoshita, Ryo', 'Nishiura, Hiroshi']",PeerJ,,,True
40ab93e7916aabc26190092d088a37d43b3240fc,PMC,"Participatory epidemiology at the neotropics: study of diseases of backyard livestock and description of hunting patterns in Uaxactún, Maya Reserve Biosphere, Guatemala",http://dx.doi.org/10.1186/s13104-016-2009-3,PMC4825071,27055652,CC BY,"BACKGROUND: The intention of the following study was to describe the interrelationship between villagers, domestic animals and wildlife at the Community Forestry Concession of Uaxactún, Guatemala by means of participatory epidemiological methods. The main focus was generating information regarding different livestock diseases considered important by villagers and their relevance, as well as obtaining knowledge concerning hunting activities and cooking methods to gain a better understanding of the interrelationship of people and animals and the diseases of their animals. RESULTS: For poultry, an overall prevalence of 41 % of Newcastle disease was found by means of the ELISA test by antibody detection, chicken being the most affected species in the village. No samples were positive to avian influenza with the HI test. No virus was isolated by means of the tracheal or cloaca swabbing of ducks. FOR HUNTING: All species could be hunted by chance at any time of the year. There was a difference in species hunted between seasons, peccaries being more frequently hunted during the dry season and in contrast, deer and wild avian during the rainy season. FOR COOKING: Villagers did not consume any raw meat. The cooking methods depended on the species. Stewing was the most favoured method for peccaries, wild birds, tepezcuintle and domestic poultry, whereas grilling was preferable for deer, roasting for armadillos and marinating for pork. CONCLUSION: According to the generated information, the most important domestic livestock species in the village are chickens and pigs, chickens being the most affected by diseases. No evident health problems on pigs were observed in this study. Hunting was shown as an activity enhanced by poverty and the lack of employment opportunities in the village and was mostly directed at larger species such as deer and peccaries. From the viewpoint of a transmission of zoonoses from animals to humans cooking methods mostly reflected a protective factor as no raw meat was eaten, stews and broths being the most common forms of cooking, involving an exposure of meat to high temperatures. Nonetheless, both agricultural and hunting activities represent a risk factor for the spread of diseases as hunters may act as mechanical vectors for different pathogens within domestic and wild animal populations.",2016 Apr 7,"['Mérida Ruíz, Samuel Alberto', 'Guerra Centeno, Dennis Sigfried', 'Bailey Leonardo, Edgar Leonel', 'Rohn, Karl', 'Kösters, Sarah', 'Kreienbrock, Lothar']",BMC Res Notes,,,True
11f2984bccfb6cb8952bceea9209357821a0583a,PMC,"Neglected Tropical Diseases in the Anthropocene: The Cases of Zika, Ebola, and Other Infections",http://dx.doi.org/10.1371/journal.pntd.0004648,PMC4825952,27058728,CC BY,,2016 Apr 8,"Hotez, Peter J.",PLoS Negl Trop Dis,,,True
90b97cb0a6ce9135c3a299462773ee94856ff22d,PMC,An eco-epidemiological study of Morbilli-related paramyxovirus infection in Madagascar bats reveals host-switching as the dominant macro-evolutionary mechanism,http://dx.doi.org/10.1038/srep23752,PMC4828640,27068130,CC BY,"An eco-epidemiological investigation was carried out on Madagascar bat communities to better understand the evolutionary mechanisms and environmental factors that affect virus transmission among bat species in closely related members of the genus Morbillivirus, currently referred to as Unclassified Morbilli-related paramyxoviruses (UMRVs). A total of 947 bats were investigated originating from 52 capture sites (22 caves, 18 buildings, and 12 outdoor sites) distributed over different bioclimatic zones of the island. Using RT-PCR targeting the L-polymerase gene of the Paramyxoviridae family, we found that 10.5% of sampled bats were infected, representing six out of seven families and 15 out of 31 species analyzed. Univariate analysis indicates that both abiotic and biotic factors may promote viral infection. Using generalized linear modeling of UMRV infection overlaid on biotic and abiotic variables, we demonstrate that sympatric occurrence of bats is a major factor for virus transmission. Phylogenetic analyses revealed that all paramyxoviruses infecting Malagasy bats are UMRVs and showed little host specificity. Analyses using the maximum parsimony reconciliation tool CoRe-PA, indicate that host-switching, rather than co-speciation, is the dominant macro-evolutionary mechanism of UMRVs among Malagasy bats.",2016 Apr 12,"['Mélade, Julien', 'Wieseke, Nicolas', 'Ramasindrazana, Beza', 'Flores, Olivier', 'Lagadec, Erwan', 'Gomard, Yann', 'Goodman, Steven M.', 'Dellagi, Koussay', 'Pascalis, Hervé']",Sci Rep,,,True
000b7d1517ceebb34e1e3e817695b6de03e2fa78,PMC,An eco-epidemiological study of Morbilli-related paramyxovirus infection in Madagascar bats reveals host-switching as the dominant macro-evolutionary mechanism,http://dx.doi.org/10.1038/srep23752,PMC4828640,27068130,CC BY,"An eco-epidemiological investigation was carried out on Madagascar bat communities to better understand the evolutionary mechanisms and environmental factors that affect virus transmission among bat species in closely related members of the genus Morbillivirus, currently referred to as Unclassified Morbilli-related paramyxoviruses (UMRVs). A total of 947 bats were investigated originating from 52 capture sites (22 caves, 18 buildings, and 12 outdoor sites) distributed over different bioclimatic zones of the island. Using RT-PCR targeting the L-polymerase gene of the Paramyxoviridae family, we found that 10.5% of sampled bats were infected, representing six out of seven families and 15 out of 31 species analyzed. Univariate analysis indicates that both abiotic and biotic factors may promote viral infection. Using generalized linear modeling of UMRV infection overlaid on biotic and abiotic variables, we demonstrate that sympatric occurrence of bats is a major factor for virus transmission. Phylogenetic analyses revealed that all paramyxoviruses infecting Malagasy bats are UMRVs and showed little host specificity. Analyses using the maximum parsimony reconciliation tool CoRe-PA, indicate that host-switching, rather than co-speciation, is the dominant macro-evolutionary mechanism of UMRVs among Malagasy bats.",2016 Apr 12,"['Mélade, Julien', 'Wieseke, Nicolas', 'Ramasindrazana, Beza', 'Flores, Olivier', 'Lagadec, Erwan', 'Gomard, Yann', 'Goodman, Steven M.', 'Dellagi, Koussay', 'Pascalis, Hervé']",Sci Rep,,,True
684dc6fccb8e9d754f09076c6a122bc0eead903f,PMC,Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection,http://dx.doi.org/10.1038/srep24179,PMC4828711,27067649,CC BY,"Recent successes with monoclonal antibody cocktails ZMapp(TM) and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab′)(2) fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab′)(2) at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs.",2016 Apr 12,"['Zheng, Xuexing', 'Wong, Gary', 'Zhao, Yongkun', 'Wang, Hualei', 'He, Shihua', 'Bi, Yuhai', 'Chen, Weijin', 'Jin, Hongli', 'Gai, Weiwei', 'Chu, Di', 'Cao, Zengguo', 'Wang, Chong', 'Fan, Quanshui', 'Chi, Hang', 'Gao, Yuwei', 'Wang, Tiecheng', 'Feng, Na', 'Yan, Feihu', 'Huang, Geng', 'Zheng, Ying', 'Li, Nan', 'Li, Yuetao', 'Qian, Jun', 'Zou, Yong', 'Kobinger, Gary', 'Gao, George Fu', 'Qiu, Xiangguo', 'Yang, Songtao', 'Xia, Xianzhu']",Sci Rep,,,True
43c81e755add9b7f05c9a15f85c54dcd0d093b0b,PMC,Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection,http://dx.doi.org/10.1038/srep24179,PMC4828711,27067649,CC BY,"Recent successes with monoclonal antibody cocktails ZMapp(TM) and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab′)(2) fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab′)(2) at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs.",2016 Apr 12,"['Zheng, Xuexing', 'Wong, Gary', 'Zhao, Yongkun', 'Wang, Hualei', 'He, Shihua', 'Bi, Yuhai', 'Chen, Weijin', 'Jin, Hongli', 'Gai, Weiwei', 'Chu, Di', 'Cao, Zengguo', 'Wang, Chong', 'Fan, Quanshui', 'Chi, Hang', 'Gao, Yuwei', 'Wang, Tiecheng', 'Feng, Na', 'Yan, Feihu', 'Huang, Geng', 'Zheng, Ying', 'Li, Nan', 'Li, Yuetao', 'Qian, Jun', 'Zou, Yong', 'Kobinger, Gary', 'Gao, George Fu', 'Qiu, Xiangguo', 'Yang, Songtao', 'Xia, Xianzhu']",Sci Rep,,,False
24fc42faaa7cf3f1b483806e77056a1d253715c5,PMC,An epidemiological study of rates of illness in passengers and crew at a busy Caribbean cruise port,http://dx.doi.org/10.1186/s12889-016-2991-3,PMC4828867,27067392,CC BY,"BACKGROUND: The Caribbean has one of the largest cruise ship industries in the world, with close to 20 million visitors per year. The potential for communicable disease outbreaks on vessels and the transmission by ship between countries is high. Barbados has one of the busiest ports in the Caribbean. Our aim was to describe and analyse the epidemiology of illnesses experienced by passengers and crew arriving at the Bridgetown Port, Barbados between 2009 and 2013. METHODS: Data on the illnesses recorded were extracted from the passenger and crew arrival registers and passenger and crew illness logs for all ships and maritime vessels arriving at Barbados’ Ports and passing through its territorial waters between January 2009 and December 2013. Data were entered into an Epi Info database and most of the analysis undertaken using Epi Info Version 7. Rates per 100,000 visits were calculated, and confidence intervals on these were derived using the software Openepi. RESULTS: There were 1031 cases of illness from over 3 million passenger visits and 1 million crew visits during this period. The overall event rate for communicable illnesses was 15.7 (95 % CI 14.4–17.1) per 100,000 passengers, and for crew was 24.0 (21.6–26.6) per 100, 000 crew. Gastroenteritis was the predominant illness experienced by passengers and crew followed by influenza. The event rate for gastroenteritis among passengers was 13.7 (12.5–15.0) per 100,000 and 14.4 (12.6, 16.5) for crew. The event rate for non-communicable illnesses was 3.4 per 100,000 passengers with myocardial infarction being the main diagnosis. The event rate for non-communicable illnesses among crew was 2.1 per 100,000, the leading cause being injuries. CONCLUSIONS: The predominant illnesses reported were gastroenteritis and influenza similar to previous published reports from around the world. This study is the first of its type in the Caribbean and the data provide a baseline for future surveillance and for comparison with other countries and regions.",2016 Apr 12,"['Marshall, Cathy Ann', 'Morris, Euclid', 'Unwin, Nigel']",BMC Public Health,,,True
85cd6377bbbcb026efd403df4177b5086df50d0d,PMC,Nosocomial infection control in healthcare settings: Protection against emerging infectious diseases,http://dx.doi.org/10.1186/s40249-016-0118-9,PMC4828876,27068809,CC BY,"The Middle East respiratory syndrome (MERS) outbreak in Korea in 2015 may be attributable to poor nosocomial infection control procedures implemented. Strict infection control measures were taken in the hospital where an imported case with MERS was treated in southern China and 53 health care workers were confirmed to be MERS-CoV negative. Infection control in healthcare settings, in which patients with emerging infectious diseases such as MERS, Ebola virus disease, and the severe acute respiratory syndrome (SARS) are diagnosed and treated, are often imperfect. When it comes to emerging or unknown infectious diseases, before the imported case was finally identified or community transmission was reported, cases have often occurred in clusters in healthcare settings. Nosocomial infection control measures should be further strengthened among the workers and inpatients in designated healthcare settings that accommodate suspected cases suffering from emerging or unknown infectious diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0118-9) contains supplementary material, which is available to authorized users.",2016 Apr 12,"['Fu, Chuanxi', 'Wang, Shengyong']",Infect Dis Poverty,,,False
ca6b85f95f1eca57c0601972938aa2b8878bc2f6,PMC,Nosocomial infection control in healthcare settings: Protection against emerging infectious diseases,http://dx.doi.org/10.1186/s40249-016-0118-9,PMC4828876,27068809,CC BY,"The Middle East respiratory syndrome (MERS) outbreak in Korea in 2015 may be attributable to poor nosocomial infection control procedures implemented. Strict infection control measures were taken in the hospital where an imported case with MERS was treated in southern China and 53 health care workers were confirmed to be MERS-CoV negative. Infection control in healthcare settings, in which patients with emerging infectious diseases such as MERS, Ebola virus disease, and the severe acute respiratory syndrome (SARS) are diagnosed and treated, are often imperfect. When it comes to emerging or unknown infectious diseases, before the imported case was finally identified or community transmission was reported, cases have often occurred in clusters in healthcare settings. Nosocomial infection control measures should be further strengthened among the workers and inpatients in designated healthcare settings that accommodate suspected cases suffering from emerging or unknown infectious diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0118-9) contains supplementary material, which is available to authorized users.",2016 Apr 12,"['Fu, Chuanxi', 'Wang, Shengyong']",Infect Dis Poverty,,,True
c5745c2eaaf8e94e31a179ce4e8775a3cd0e6745,PMC,Genetic Deletion of ACE2 Induces Vascular Dysfunction in C57BL/6 Mice: Role of Nitric Oxide Imbalance and Oxidative Stress,http://dx.doi.org/10.1371/journal.pone.0150255,PMC4829150,27070147,CC BY,"Accumulating evidence indicates that angiotensin-converting enzyme 2 (ACE2) plays a critical role in cardiovascular homeostasis, and its altered expression is associated with major cardiac and vascular disorders. The aim of this study was to evaluate the regulation of vascular function and assess the vascular redox balance in ACE2-deficient (ACE2(-/y)) animals. Experiments were performed in 20–22 week-old C57BL/6 and ACE2(-/y) male mice. Evaluation of endothelium-dependent and -independent relaxation revealed an impairment of in vitro and in vivo vascular function in ACE2(-/y) mice. Drastic reduction in eNOS expression at both protein and mRNA levels, and a decrease in (•)NO concentrations were observed in aortas of ACE2(-/y) mice in comparison to controls. Consistently, these mice presented a lower plasma and urine nitrite concentration, confirming reduced (•)NO availability in ACE2-deficient animals. Lipid peroxidation was significantly increased and superoxide dismutase activity was decreased in aorta homogenates of ACE2(-/y) mice, indicating impaired antioxidant capacity. Taken together, our data indicate, that ACE2 regulates vascular function by modulating nitric oxide release and oxidative stress. In conclusion, we elucidate mechanisms by which ACE2 is involved in the maintenance of vascular homeostasis. Furthermore, these findings provide insights into the role of the renin-angiotensin system in both vascular and systemic redox balance.",2016 Apr 12,"['Rabelo, Luiza A.', 'Todiras, Mihail', 'Nunes-Souza, Valéria', 'Qadri, Fatimunnisa', 'Szijártó, István András', 'Gollasch, Maik', 'Penninger, Josef M.', 'Bader, Michael', 'Santos, Robson A.', 'Alenina, Natalia']",PLoS One,,,True
9b6d81e0b5b4f49fcdf34be409406bc43988281e,PMC,Genetic Deletion of ACE2 Induces Vascular Dysfunction in C57BL/6 Mice: Role of Nitric Oxide Imbalance and Oxidative Stress,http://dx.doi.org/10.1371/journal.pone.0150255,PMC4829150,27070147,CC BY,"Accumulating evidence indicates that angiotensin-converting enzyme 2 (ACE2) plays a critical role in cardiovascular homeostasis, and its altered expression is associated with major cardiac and vascular disorders. The aim of this study was to evaluate the regulation of vascular function and assess the vascular redox balance in ACE2-deficient (ACE2(-/y)) animals. Experiments were performed in 20–22 week-old C57BL/6 and ACE2(-/y) male mice. Evaluation of endothelium-dependent and -independent relaxation revealed an impairment of in vitro and in vivo vascular function in ACE2(-/y) mice. Drastic reduction in eNOS expression at both protein and mRNA levels, and a decrease in (•)NO concentrations were observed in aortas of ACE2(-/y) mice in comparison to controls. Consistently, these mice presented a lower plasma and urine nitrite concentration, confirming reduced (•)NO availability in ACE2-deficient animals. Lipid peroxidation was significantly increased and superoxide dismutase activity was decreased in aorta homogenates of ACE2(-/y) mice, indicating impaired antioxidant capacity. Taken together, our data indicate, that ACE2 regulates vascular function by modulating nitric oxide release and oxidative stress. In conclusion, we elucidate mechanisms by which ACE2 is involved in the maintenance of vascular homeostasis. Furthermore, these findings provide insights into the role of the renin-angiotensin system in both vascular and systemic redox balance.",2016 Apr 12,"['Rabelo, Luiza A.', 'Todiras, Mihail', 'Nunes-Souza, Valéria', 'Qadri, Fatimunnisa', 'Szijártó, István András', 'Gollasch, Maik', 'Penninger, Josef M.', 'Bader, Michael', 'Santos, Robson A.', 'Alenina, Natalia']",PLoS One,,,False
66cda0b3d87b530e2659f8ac93a74ed963e9645e,PMC,Picoliter Well Array Chip-Based Digital Recombinase Polymerase Amplification for Absolute Quantification of Nucleic Acids,http://dx.doi.org/10.1371/journal.pone.0153359,PMC4830604,27074005,CC BY,"Absolute, precise quantification methods expand the scope of nucleic acids research and have many practical applications. Digital polymerase chain reaction (dPCR) is a powerful method for nucleic acid detection and absolute quantification. However, it requires thermal cycling and accurate temperature control, which are difficult in resource-limited conditions. Accordingly, isothermal methods, such as recombinase polymerase amplification (RPA), are more attractive. We developed a picoliter well array (PWA) chip with 27,000 consistently sized picoliter reactions (314 pL) for isothermal DNA quantification using digital RPA (dRPA) at 39°C. Sample loading using a scraping liquid blade was simple, fast, and required small reagent volumes (i.e., <20 μL). Passivating the chip surface using a methoxy-PEG-silane agent effectively eliminated cross-contamination during dRPA. Our creative optical design enabled wide-field fluorescence imaging in situ and both end-point and real-time analyses of picoliter wells in a 6-cm(2) area. It was not necessary to use scan shooting and stitch serial small images together. Using this method, we quantified serial dilutions of a Listeria monocytogenes gDNA stock solution from 9 × 10(-1) to 4 × 10(-3) copies per well with an average error of less than 11% (N = 15). Overall dRPA-on-chip processing required less than 30 min, which was a 4-fold decrease compared to dPCR, requiring approximately 2 h. dRPA on the PWA chip provides a simple and highly sensitive method to quantify nucleic acids without thermal cycling or precise micropump/microvalve control. It has applications in fast field analysis and critical clinical diagnostics under resource-limited settings.",2016 Apr 13,"['Li, Zhao', 'Liu, Yong', 'Wei, Qingquan', 'Liu, Yuanjie', 'Liu, Wenwen', 'Zhang, Xuelian', 'Yu, Yude']",PLoS One,,,True
450811c073efd4b4b2140c1ce4ad035e58ee834c,PMC,Picoliter Well Array Chip-Based Digital Recombinase Polymerase Amplification for Absolute Quantification of Nucleic Acids,http://dx.doi.org/10.1371/journal.pone.0153359,PMC4830604,27074005,CC BY,"Absolute, precise quantification methods expand the scope of nucleic acids research and have many practical applications. Digital polymerase chain reaction (dPCR) is a powerful method for nucleic acid detection and absolute quantification. However, it requires thermal cycling and accurate temperature control, which are difficult in resource-limited conditions. Accordingly, isothermal methods, such as recombinase polymerase amplification (RPA), are more attractive. We developed a picoliter well array (PWA) chip with 27,000 consistently sized picoliter reactions (314 pL) for isothermal DNA quantification using digital RPA (dRPA) at 39°C. Sample loading using a scraping liquid blade was simple, fast, and required small reagent volumes (i.e., <20 μL). Passivating the chip surface using a methoxy-PEG-silane agent effectively eliminated cross-contamination during dRPA. Our creative optical design enabled wide-field fluorescence imaging in situ and both end-point and real-time analyses of picoliter wells in a 6-cm(2) area. It was not necessary to use scan shooting and stitch serial small images together. Using this method, we quantified serial dilutions of a Listeria monocytogenes gDNA stock solution from 9 × 10(-1) to 4 × 10(-3) copies per well with an average error of less than 11% (N = 15). Overall dRPA-on-chip processing required less than 30 min, which was a 4-fold decrease compared to dPCR, requiring approximately 2 h. dRPA on the PWA chip provides a simple and highly sensitive method to quantify nucleic acids without thermal cycling or precise micropump/microvalve control. It has applications in fast field analysis and critical clinical diagnostics under resource-limited settings.",2016 Apr 13,"['Li, Zhao', 'Liu, Yong', 'Wei, Qingquan', 'Liu, Yuanjie', 'Liu, Wenwen', 'Zhang, Xuelian', 'Yu, Yude']",PLoS One,,,False
953d3fece0d805133c1e9a3f02a3f0711dab6161,PMC,Picoliter Well Array Chip-Based Digital Recombinase Polymerase Amplification for Absolute Quantification of Nucleic Acids,http://dx.doi.org/10.1371/journal.pone.0153359,PMC4830604,27074005,CC BY,"Absolute, precise quantification methods expand the scope of nucleic acids research and have many practical applications. Digital polymerase chain reaction (dPCR) is a powerful method for nucleic acid detection and absolute quantification. However, it requires thermal cycling and accurate temperature control, which are difficult in resource-limited conditions. Accordingly, isothermal methods, such as recombinase polymerase amplification (RPA), are more attractive. We developed a picoliter well array (PWA) chip with 27,000 consistently sized picoliter reactions (314 pL) for isothermal DNA quantification using digital RPA (dRPA) at 39°C. Sample loading using a scraping liquid blade was simple, fast, and required small reagent volumes (i.e., <20 μL). Passivating the chip surface using a methoxy-PEG-silane agent effectively eliminated cross-contamination during dRPA. Our creative optical design enabled wide-field fluorescence imaging in situ and both end-point and real-time analyses of picoliter wells in a 6-cm(2) area. It was not necessary to use scan shooting and stitch serial small images together. Using this method, we quantified serial dilutions of a Listeria monocytogenes gDNA stock solution from 9 × 10(-1) to 4 × 10(-3) copies per well with an average error of less than 11% (N = 15). Overall dRPA-on-chip processing required less than 30 min, which was a 4-fold decrease compared to dPCR, requiring approximately 2 h. dRPA on the PWA chip provides a simple and highly sensitive method to quantify nucleic acids without thermal cycling or precise micropump/microvalve control. It has applications in fast field analysis and critical clinical diagnostics under resource-limited settings.",2016 Apr 13,"['Li, Zhao', 'Liu, Yong', 'Wei, Qingquan', 'Liu, Yuanjie', 'Liu, Wenwen', 'Zhang, Xuelian', 'Yu, Yude']",PLoS One,,,False
7fddc064e4c4aac26961aa413f27193ad175095b,PMC,"International Air Travel to Ohio, USA, and the Impact on Malaria, Influenza, and Hepatitis A",http://dx.doi.org/10.1155/2016/8258946,PMC4830737,27123365,CC BY,"The State of Ohio led the United States in measles in 2014, ostensibly related to international air travel (IAT), and ranked lower than 43 other states in infectious disease outbreak preparedness. We conducted a retrospective cohort study using surveillance data of the total Ohio population of 11 million from 2010 through 2014 with a nested case control of air travelers to determine the risk of malaria, seasonal influenza hospitalizations (IH), and hepatitis A (HA) disease related to international travel and to estimate the association with domestic enplanement. IAT appeared protective for HA and IH with a risk of 0.031 (.02–.04) but for malaria was 2.7 (2.07–3.62). Enplanement increased the risk for nonendemic M 3.5 (2.5–4.9) and for HA and IH 1.39 (1.34–1.44). IAT's ratio of relative risk (RRR) of malaria to HA and IH was 87.1 (55.8–136) greater than 219 times versus domestic enplanement which was protective for malaria at 0.397 (0.282–0.559). Malaria is correlated with IAT with cases increasing by 6.9 for every 10,000 passports issued.",2016 Mar 31,"['Brannen, Donald E.', 'Alhammad, Ali', 'Branum, Melissa', 'Schmitt, Amy']",Scientifica (Cairo),,,True
57b8e034f902f2883dbbafaeef554cb2deb64963,PMC,Silver Nanoparticles Induce HePG-2 Cells Apoptosis Through ROS-Mediated Signaling Pathways,http://dx.doi.org/10.1186/s11671-016-1419-4,PMC4830774,27075340,CC BY,"Recently, silver nanoparticles (AgNPs) have been shown to provide a novel approach to overcome tumors, especially those of hepatocarcinoma. However, the anticancer mechanism of silver nanoparticles is unclear. Thus, the purpose of this study was to estimate the effect of AgNPs on proliferation and activation of ROS-mediated signaling pathway on human hepatocellular carcinoma HePG-2 cells. A simple chemical method for preparing AgNPs with superior anticancer activity has been showed in this study. AgNPs were detected by transmission electronic microscopy (TEM) and energy dispersive X-ray (EDX). The size distribution and zeta potential of silver nanoparticles were detected by Zetasizer Nano. The average size of AgNPs (2 nm) observably increased the cellular uptake by endocytosis. AgNPs markedly inhibited the proliferation of HePG-2 cells through induction of apoptosis with caspase-3 activation and PARP cleavage. AgNPs with dose-dependent manner significantly increased the apoptotic cell population (sub-G1). Furthermore, AgNP-induced apoptosis was found dependent on the overproduction of reactive oxygen species (ROS) and affecting of MAPKs and AKT signaling and DNA damage-mediated p53 phosphorylation to advance HePG-2 cells apoptosis. Therefore, our results show that the mechanism of ROS-mediated signaling pathways may provide useful information in AgNP-induced HePG-2 cell apoptosis.",2016 Apr 14,"['Zhu, Bing', 'Li, Yinghua', 'Lin, Zhengfang', 'Zhao, Mingqi', 'Xu, Tiantian', 'Wang, Changbing', 'Deng, Ning']",Nanoscale Res Lett,,,True
f87fb7ecfabe0bae476e587f8c5eb01b15b24db0,PMC,Finite Element Analysis on Nanomechanical Detection of Small Particles: Toward Virus Detection,http://dx.doi.org/10.3389/fmicb.2016.00488,PMC4830830,27148181,CC BY,"Detection of small particles, including viruses and particulate matter (PM), has been attracting much attention in light of increasing need for environmental monitoring. Owing to their high versatility, a nanomechanical sensor is one of the most promising sensors which can be adapted to various monitoring systems. In this study, we present an optimization strategy to efficiently detect small particles with nanomechanical sensors. Adsorption of particles on the receptor layer of nanomechanical sensors and the resultant signal are analyzed using finite element analysis (FEA). We investigate the effect of structural parameters (e.g., adsorption position and embedded depth of a particle and thickness of the receptor layer) and elastic properties of the receptor layer (e.g., Young's modulus and Poisson's ratio) on the sensitivity. It is found that a membrane-type surface stress sensors (MSS) has the potential for robust detection of small particles.",2016 Apr 14,"['Imamura, Gaku', 'Shiba, Kota', 'Yoshikawa, Genki']",Front Microbiol,,,True
fe58b17bca43d017cf1af9b5748147b25f067b7d,PMC,The Use of Kosher Phenotyping for Mapping QTL Affecting Susceptibility to Bovine Respiratory Disease,http://dx.doi.org/10.1371/journal.pone.0153423,PMC4831767,27077383,CC BY,"Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in feedlot cattle, caused by multiple pathogens that become more virulent in response to stress. As clinical signs often go undetected and various preventive strategies failed, identification of genes affecting BRD is essential for selection for resistance. Selective DNA pooling (SDP) was applied in a genome wide association study (GWAS) to map BRD QTLs in Israeli Holstein male calves. Kosher scoring of lung adhesions was used to allocate 122 and 62 animals to High (Glatt Kosher) and Low (Non-Kosher) resistant groups, respectively. Genotyping was performed using the Illumina BovineHD BeadChip according to the Infinium protocol. Moving average of -logP was used to map QTLs and Log drop was used to define their boundaries (QTLRs). The combined procedure was efficient for high resolution mapping. Nineteen QTLRs distributed over 13 autosomes were found, some overlapping previous studies. The QTLRs contain polymorphic functional and expression candidate genes to affect kosher status, with putative immunological and wound healing activities. Kosher phenotyping was shown to be a reliable means to map QTLs affecting BRD morbidity.",2016 Apr 14,"['Lipkin, Ehud', 'Strillacci, Maria Giuseppina', 'Eitam, Harel', 'Yishay, Moran', 'Schiavini, Fausta', 'Soller, Morris', 'Bagnato, Alessandro', 'Shabtay, Ariel']",PLoS One,,,True
1ce05f10fab075f30d07b091fcc8530aa0b6b252,PMC,The Use of Kosher Phenotyping for Mapping QTL Affecting Susceptibility to Bovine Respiratory Disease,http://dx.doi.org/10.1371/journal.pone.0153423,PMC4831767,27077383,CC BY,"Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in feedlot cattle, caused by multiple pathogens that become more virulent in response to stress. As clinical signs often go undetected and various preventive strategies failed, identification of genes affecting BRD is essential for selection for resistance. Selective DNA pooling (SDP) was applied in a genome wide association study (GWAS) to map BRD QTLs in Israeli Holstein male calves. Kosher scoring of lung adhesions was used to allocate 122 and 62 animals to High (Glatt Kosher) and Low (Non-Kosher) resistant groups, respectively. Genotyping was performed using the Illumina BovineHD BeadChip according to the Infinium protocol. Moving average of -logP was used to map QTLs and Log drop was used to define their boundaries (QTLRs). The combined procedure was efficient for high resolution mapping. Nineteen QTLRs distributed over 13 autosomes were found, some overlapping previous studies. The QTLRs contain polymorphic functional and expression candidate genes to affect kosher status, with putative immunological and wound healing activities. Kosher phenotyping was shown to be a reliable means to map QTLs affecting BRD morbidity.",2016 Apr 14,"['Lipkin, Ehud', 'Strillacci, Maria Giuseppina', 'Eitam, Harel', 'Yishay, Moran', 'Schiavini, Fausta', 'Soller, Morris', 'Bagnato, Alessandro', 'Shabtay, Ariel']",PLoS One,,,False
1e71a51670cdda3d92a1f182967d78dca3bb5d44,PMC,Retinoic acid facilitates inactivated transmissible gastroenteritis virus induction of CD8(+) T-cell migration to the porcine gut,http://dx.doi.org/10.1038/srep24152,PMC4832189,27080036,CC BY,"The digestive tract is the entry site for transmissible gastroenteritis virus (TGEV). TGEV transmission can be prevented if local immunity is established with increased lymphocytes. The current parenteral mode of vaccination stimulates systemic immunity well, but it does not induce sufficient mucosal immunity. Retinoic acid (RA) plays an important role in the induction of cells that imprint gut-homing molecules. We examined whether RA assist parenteral vaccination of pigs could improve mucosal immunity. We demonstrated that elevated numbers of gut-homing CD8(+) T cells (which express α4β7 and CCR9 molecules) were presented in porcine inguinal lymph nodes and were recruited to the small intestine by RA. Intestinal mucosal immunity (IgA titre) and systemic immunity (serum IgG titre) were enhanced by RA. Therefore, we hypothesized that RA could induce DCs to form an immature mucosal phenotype and could recruit them to the small intestinal submucosa. Porcine T-cells expressed β7 integrin and CCR9 receptors and migrated to CCL25 by a mechanism that was dependent of activation by RA-pretreated DCs, rather than direct activation by RA. Together, our results provide powerful evidence that RA can assist whole inactivated TGEV (WI-TGEV) via subcutaneous (s.c.) immunization to generate intestinal immunity, and offer new vaccination strategies against TGEV.",2016 Apr 15,"['Chen, Xiaojuan', 'Tu, Chongzhi', 'Qin, Tao', 'Zhu, Liqi', 'Yin, Yinyan', 'Yang, Qian']",Sci Rep,,,True
4ccdf68a98517afb602bd6ab2eca8e77fac05830,PMC,Reverse Transcription Cross-Priming Amplification–Nucleic Acid Test Strip for Rapid Detection of Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.1038/srep24702,PMC4835727,27090105,CC BY,"Porcine epidemic diarrhea virus (PEDV) is a highly transmissible coronavirus that causes a severe enteric disease particularly in neonatal piglets. In this study, a rapid method for detecting PEDV was developed based on cross-priming amplification and nucleic acid test strip(CPA-NATS). Five primers specific for the N gene sequence of PEDV were used for the cross-priming amplification. Detection of amplification products based on labeled probe primers was conducted with strip binding antibody of labeled markers. The CPA method was evaluated and compared with a PCR method. The reverse transcription CPA system was further optimized for detecting PEDV RNA in clinical specimens. Results showed that the method was highly specific for the detection of PEDV, and had the same sensitivity as PCR, with detection limit of 10(−6) diluted plasmid containing the target gene of PEDV. It was also successfully applied to detecting PEDV in clinical specimens. The reverse transcription CPA-NATS detection system established in this study offers a specific, sensitive, rapid, and simple detection tool for screening PEDV, which can contribute to strategies in the effective control of PEDV in swine.",2016 Apr 19,"['Wang, Feng-Xue', 'Yuan, Dan-Yi', 'Jin, Ya-Nan', 'Hu, Lin', 'Sun, Zhi-Yong', 'He, Qian', 'Zhao, Shi-Hua', 'Zhan, Shu-Bai', 'Wen, Yong-Jun']",Sci Rep,,,True
213fdedff656134ff3dbe24a7d7bbba61d13baa1,PMC,"Blockage of indoleamine 2,3-dioxygenase regulates Japanese encephalitis via enhancement of type I/II IFN innate and adaptive T-cell responses",http://dx.doi.org/10.1186/s12974-016-0551-5,PMC4835894,27090635,CC BY,"BACKGROUND: Japanese encephalitis (JE), a leading cause of viral encephalitis, is characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV). Indoleamine 2,3-dioxygenase (IDO) has been identified as an enzyme associated with immunoregulatory function. Although the regulatory role of IDO in viral replication has been postulated, the in vivo role of IDO activity has not been fully addressed in neurotropic virus-caused encephalitis. METHODS: Mice in which IDO activity was inhibited by genetic ablation or using a specific inhibitor were examined for mortality and clinical signs after infection. Neuroinflammation was evaluated by central nervous system (CNS) infiltration of leukocytes and cytokine expression. IDO expression, viral burden, JEV-specific T-cell, and type I/II interferon (IFN-I/II) innate responses were also analyzed. RESULTS: Elevated expression of IDO activity in myeloid and neuron cells of the lymphoid and CNS tissues was closely associated with clinical signs of JE. Furthermore, inhibition of IDO activity enhanced resistance to JE, reduced the viral burden in lymphoid and CNS tissues, and resulted in early and increased CNS infiltration by Ly-6C(hi) monocytes, NK, CD4(+), and CD8(+) T-cells. JE amelioration in IDO-ablated mice was also associated with enhanced NK and JEV-specific T-cell responses. More interestingly, IDO ablation induced rapid enhancement of type I IFN (IFN-I) innate responses in CD11c(+) dendritic cells (DCs), including conventional and plasmacytoid DCs, following JEV infection. This enhanced IFN-I innate response in IDO-ablated CD11c(+) DCs was coupled with strong induction of PRRs (RIG-I, MDA5), transcription factors (IRF7, STAT1), and antiviral ISG genes (Mx1, Mx2, ISG49, ISG54, ISG56). IDO ablation also enhanced the IFN-I innate response in neuron cells, which may delay the spread of virus in the CNS. Finally, we identified that IDO ablation in myeloid cells derived from hematopoietic stem cells (HSCs) dominantly contributed to JE amelioration and that HSC-derived leukocytes played a key role in the enhanced IFN-I innate responses in the IDO-ablated environment. CONCLUSIONS: Inhibition of IDO activity ameliorated JE via enhancement of antiviral IFN-I/II innate and adaptive T-cell responses and increased CNS infiltration of peripheral leukocytes. Therefore, our data provide valuable insight into the use of IDO inhibition by specific inhibitors as a promising tool for therapeutic and prophylactic strategies against viral encephalitis caused by neurotropic viruses.",2016 Apr 18,"['Kim, Seong Bum', 'Choi, Jin Young', 'Uyangaa, Erdenebileg', 'Patil, Ajit Mahadev', 'Hossain, Ferdaus Mohd Altaf', 'Hur, Jin', 'Park, Sang-Youel', 'Lee, John-Hwa', 'Kim, Koanhoi', 'Eo, Seong Kug']",J Neuroinflammation,,,True
4c1e7d31ff353e605f4211eebae16eaea9defed6,PMC,A Dimerization-Dependent Mechanism Drives the Endoribonuclease Function of Porcine Reproductive and Respiratory Syndrome Virus nsp11,http://dx.doi.org/10.1128/JVI.03065-15,PMC4836315,26912626,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) RNA endoribonuclease nsp11 belongs to the XendoU superfamily and plays a crucial role in arterivirus replication. Here, we report the first crystal structure of the arterivirus nsp11 protein from PRRSV, which exhibits a unique structure and assembles into an asymmetric dimer whose structure is completely different from the hexameric structure of coronavirus nsp15. However, the structures of the PRRSV nsp11 and coronavirus nsp15 catalytic domains were perfectly superimposed, especially in the “active site loop” (His129 to His144) and “supporting loop” (Val162 to Thr179) regions. Importantly, our biochemical data demonstrated that PRRSV nsp11 exists mainly as a dimer in solution. Mutations of the major dimerization site determinants (Ser74 and Phe76) in the dimerization interface destabilized the dimer in solution and severely diminished endoribonuclease activity, indicating that the dimer is the biologically functional unit. In the dimeric structure, the active site loop and supporting loop are packed against one another and stabilized by monomer-monomer interactions. These findings may help elucidate the mechanism underlying arterivirus replication and may represent great potential for the development of antiviral drugs. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) is a member of the family Arteriviridae, order Nidovirales. PRRSV is a major agent of respiratory diseases in pigs, causing tremendous economic losses to the swine industry worldwide. The PRRSV nsp11 endoribonuclease plays a vital role in arterivirus replication, but its precise roles and mechanisms of action are poorly understood. Here, we report the first dimeric structure of the arterivirus nsp11 from PRRSV at 2.75-Å resolution. Structural and biochemical experiments demonstrated that nsp11 exists mainly as a dimer in solution and that nsp11 may be fully active as a dimer. Mutagenesis and structural analysis revealed NendoU active site residues, which are conserved throughout the order Nidovirales (families Arteriviridae and Coronaviridae) and the major determinants of dimerization (Ser74 and Phe76) in Arteriviridae. Importantly, these findings may provide a new structural basis for antiviral drug development.",2016 Apr 14,"['Shi, Yuejun', 'Li, Youwen', 'Lei, Yingying', 'Ye, Gang', 'Shen, Zhou', 'Sun, Limeng', 'Luo, Rui', 'Wang, Dang', 'Fu, Zhen F.', 'Xiao, Shaobo', 'Peng, Guiqing']",J Virol,,,True
1bab633e4d3ab1ed30599369e8654c235256c5cd,PMC,The Proteolytic Activation of (H3N2) Influenza A Virus Hemagglutinin Is Facilitated by Different Type II Transmembrane Serine Proteases,http://dx.doi.org/10.1128/JVI.02693-15,PMC4836353,26889029,CC BY,"Cleavage of influenza virus hemagglutinin (HA) by host cell proteases is necessary for viral activation and infectivity. In humans and mice, members of the type II transmembrane protease family (TTSP), e.g., TMPRSS2, TMPRSS4, and TMPRSS11d (HAT), have been shown to cleave influenza virus HA for viral activation and infectivity in vitro. Recently, we reported that inactivation of a single HA-activating protease gene, Tmprss2, in knockout mice inhibits the spread of H1N1 influenza viruses. However, after infection of Tmprss2 knockout mice with an H3N2 influenza virus, only a slight increase in survival was observed, and mice still lost body weight. In this study, we investigated an additional trypsin-like protease, TMPRSS4. Both TMPRSS2 and TMPRSS4 are expressed in the same cell types of the mouse lung. Deletion of Tmprss4 alone in knockout mice does not protect them from body weight loss and death upon infection with H3N2 influenza virus. In contrast, Tmprss2(−/−) Tmprss4(−/−) double-knockout mice showed a remarkably reduced virus spread and lung pathology, in addition to reduced body weight loss and mortality. Thus, our results identified TMPRSS4 as a second host cell protease that, in addition to TMPRSS2, is able to activate the HA of H3N2 influenza virus in vivo. IMPORTANCE Influenza epidemics and recurring pandemics are responsible for significant global morbidity and mortality. Due to high variability of the virus genome, resistance to available antiviral drugs is frequently observed, and new targets for treatment of influenza are needed. Host cell factors essential for processing of the virus hemagglutinin represent very suitable drug targets because the virus is dependent on these host factors for replication. We reported previously that Tmprss2-deficient mice are protected against H1N1 virus infections, but only marginal protection against H3N2 virus infections was observed. Here we show that deletion of two host protease genes, Tmprss2 and Tmprss4, strongly reduced viral spread as well as lung pathology and resulted in increased survival after H3N2 virus infection. Thus, TMPRSS4 represents another host cell factor that is involved in cleavage activation of H3N2 influenza viruses in vivo.",2016 Apr 14,"['Kühn, Nora', 'Bergmann, Silke', 'Kösterke, Nadine', 'Lambertz, Ruth L. O.', 'Keppner, Anna', 'van den Brand, Judith M. A.', 'Pöhlmann, Stefan', 'Weiß, Siegfried', 'Hummler, Edith', 'Hatesuer, Bastian', 'Schughart, Klaus']",J Virol,,,True
381bb3c674e68a97e38efe5d6f9952c7a64522d3,PMC,Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs,http://dx.doi.org/10.1371/journal.pone.0151922,PMC4836704,27093541,CC BY,"Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV). Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticle (PLGA-NP) based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2) chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant) significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.",2016 Apr 19,"['Hiremath, Jagadish', 'Kang, Kyung-il', 'Xia, Ming', 'Elaish, Mohamed', 'Binjawadagi, Basavaraj', 'Ouyang, Kang', 'Dhakal, Santosh', 'Arcos, Jesus', 'Torrelles, Jordi B.', 'Jiang, X.', 'Lee, Chang Won', 'Renukaradhya, Gourapura J.']",PLoS One,,,True
2b2b4954a960745a09009e9de6d1cb87358bfa6a,PMC,Development of Monoclonal Antibody and Diagnostic Test for Middle East Respiratory Syndrome Coronavirus Using Cell-Free Synthesized Nucleocapsid Antigen,http://dx.doi.org/10.3389/fmicb.2016.00509,PMC4837155,27148198,CC BY,"Protein nativity is one of the most critical factors for the quality of antigens used as immunogens and the reactivities of the resultant antibodies. The preparation and purification of native viral antigens in conventional cell-based protein expression systems are often accompanied by technical hardships. These challenges are attributable mainly to protein aggregation and insolubility during expression and purification, as well as to very low expression levels associated with the toxicity of some viral proteins. Here, we describe a novel approach for the production of monoclonal antibodies (mAbs) against nucleocapsid protein (NP) of the Middle East respiratory syndrome coronavirus (MERS-CoV). Using a wheat germ cell-free protein synthesis system, we successfully prepared large amounts of MERS-CoV NP antigen in a state that was highly soluble and intact for immunization. Following mouse immunization and hybridoma generation, we selected seven hybridoma clones that produced mAbs with exclusive reactivity against MERS-CoV NP. Epitope mapping and subsequent bioinformatic analysis revealed that these mAbs recognized epitopes located within relatively highly conserved regions of the MERS-CoV amino-acid sequence. Consistently, the mAbs exhibited no obvious cross-reactivity with NPs derived from other related viruses, including SARS coronavirus. After determining the optimal combinations of these mAbs, we developed an enzyme-linked immunosorbent assay and a rapid immunochromatographic antigen detection test that can be reliably used for laboratory diagnosis of MERS-CoV. Thus, this study provides strong evidence that the wheat germ cell-free system is useful for the production of diagnostic mAbs against emerging pathogens.",2016 Apr 20,"['Yamaoka, Yutaro', 'Matsuyama, Shutoku', 'Fukushi, Shuetsu', 'Matsunaga, Satoko', 'Matsushima, Yuki', 'Kuroyama, Hiroyuki', 'Kimura, Hirokazu', 'Takeda, Makoto', 'Chimuro, Tomoyuki', 'Ryo, Akihide']",Front Microbiol,,,True
a413230495919e899e941fe5c2993c7cec504d4a,PMC,Structural characterization of recombinant IAV polymerase reveals a stable complex between viral PA-PB1 heterodimer and host RanBP5,http://dx.doi.org/10.1038/srep24727,PMC4837377,27095520,CC BY,"The genome of influenza A virus (IAV) comprises eight RNA segments (vRNA) which are transcribed and replicated by the heterotrimeric IAV RNA-dependent RNA-polymerase (RdRp). RdRp consists of three subunits (PA, PB1 and PB2) and binds both the highly conserved 3′- and 5′-ends of the vRNA segment. The IAV RdRp is an important antiviral target, but its structural mechanism has remained largely elusive to date. By applying a polyprotein strategy, we produced RdRp complexes and define a minimal human IAV RdRp core complex. We show that PA-PB1 forms a stable heterodimeric submodule that can strongly interact with 5′-vRNA. In contrast, 3′-vRNA recognition critically depends on the PB2 N-terminal domain. Moreover, we demonstrate that PA-PB1 forms a stable and stoichiometric complex with host nuclear import factor RanBP5 that can be modelled using SAXS and we show that the PA-PB1-RanPB5 complex is no longer capable of 5′-vRNA binding. Our results provide further evidence for a step-wise assembly of IAV structural components, regulated by nuclear transport mechanisms and host factor binding.",2016 Apr 20,"['Swale, Christopher', 'Monod, Alexandre', 'Tengo, Laura', 'Labaronne, Alice', 'Garzoni, Frédéric', 'Bourhis, Jean-Marie', 'Cusack, Stephen', 'Schoehn, Guy', 'Berger, Imre', 'Ruigrok, Rob WH', 'Crépin, Thibaut']",Sci Rep,,,True
8cd08e9912baa6d4b3d41a42d02951c098044045,PMC,Structural characterization of recombinant IAV polymerase reveals a stable complex between viral PA-PB1 heterodimer and host RanBP5,http://dx.doi.org/10.1038/srep24727,PMC4837377,27095520,CC BY,"The genome of influenza A virus (IAV) comprises eight RNA segments (vRNA) which are transcribed and replicated by the heterotrimeric IAV RNA-dependent RNA-polymerase (RdRp). RdRp consists of three subunits (PA, PB1 and PB2) and binds both the highly conserved 3′- and 5′-ends of the vRNA segment. The IAV RdRp is an important antiviral target, but its structural mechanism has remained largely elusive to date. By applying a polyprotein strategy, we produced RdRp complexes and define a minimal human IAV RdRp core complex. We show that PA-PB1 forms a stable heterodimeric submodule that can strongly interact with 5′-vRNA. In contrast, 3′-vRNA recognition critically depends on the PB2 N-terminal domain. Moreover, we demonstrate that PA-PB1 forms a stable and stoichiometric complex with host nuclear import factor RanBP5 that can be modelled using SAXS and we show that the PA-PB1-RanPB5 complex is no longer capable of 5′-vRNA binding. Our results provide further evidence for a step-wise assembly of IAV structural components, regulated by nuclear transport mechanisms and host factor binding.",2016 Apr 20,"['Swale, Christopher', 'Monod, Alexandre', 'Tengo, Laura', 'Labaronne, Alice', 'Garzoni, Frédéric', 'Bourhis, Jean-Marie', 'Cusack, Stephen', 'Schoehn, Guy', 'Berger, Imre', 'Ruigrok, Rob WH', 'Crépin, Thibaut']",Sci Rep,,,False
78057e9db3bebe6ecfc99fbc036414ebd4115cfd,PMC,Diminished COX-2/PGE(2)-Mediated Antiviral Response Due to Impaired NOX/MAPK Signaling in G6PD-Knockdown Lung Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0153462,PMC4838297,27097228,CC BY,"Glucose-6-phosphate dehydrogenase (G6PD) provides the reducing agent NADPH to meet the cellular needs for reductive biosynthesis and the maintenance of redox homeostasis. G6PD-deficient cells experience a high level of oxidative stress and an increased susceptibility to viral infections. Cyclooxygenase-2 (COX-2) is a key mediator in the regulation of viral replication and inflammatory response. In the current study, the role of G6PD on the inflammatory response was determined in both scramble control and G6PD-knockdown (G6PD-kd) A549 cells upon tumor necrosis factor-α (TNF-α) stimulation. A decreased expression pattern of induced COX-2 and reduced production of downstream PGE(2) occurred upon TNF-α stimulation in G6PD-kd A549 cells compared with scramble control A549 cells. TNF-α-induced antiviral activity revealed that decreased COX-2 expression enhanced the susceptibility to coronavirus 229E infection in G6PD-kd A549 cells and was a result of the decreased phosphorylation levels of MAPK (p38 and ERK1/2) and NF-κB. The impaired inflammatory response in G6PD-kd A549 cells was found to be mediated through NADPH oxidase (NOX) signaling as elucidated by cell pretreatment with a NOX2-siRNA or NOX inhibitor, diphenyleneiodonium chloride (DPI). In addition, NOX activity with TNF-α treatment in G6PD-kd A549 cells was not up-regulated and was coupled with a decrease in NOX subunit expression at the transcriptional level, implying that TNF-α-mediated NOX signaling requires the participation of G6PD. Together, these data suggest that G6PD deficiency affects the cellular inflammatory response and the decreased TNF-α-mediated antiviral response in G6PD-kd A549 cells is a result of dysregulated NOX/MAPK/NF-κB/COX-2 signaling.",2016 Apr 20,"['Lin, Hsin-Ru', 'Wu, Yi-Hsuan', 'Yen, Wei-Chen', 'Yang, Chuen-Mao', 'Chiu, Daniel Tsun-Yee']",PLoS One,,,True
058b0cc7cecd43d80ed47196cb5376fa10efb58a,PMC,Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?,http://dx.doi.org/10.1371/journal.pone.0152481,PMC4838299,27096199,CC BY,"BACKGROUND: Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. OBJECTIVES: To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). METHODS: We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. RESULTS: 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. CONCLUSION: The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role.",2016 Apr 20,"['Cebey-López, Miriam', 'Herberg, Jethro', 'Pardo-Seco, Jacobo', 'Gómez-Carballa, Alberto', 'Martinón-Torres, Nazareth', 'Salas, Antonio', 'Martinón-Sánchez, José María', 'Justicia, Antonio', 'Rivero-Calle, Irene', 'Sumner, Edward', 'Fink, Colin', 'Martinón-Torres, Federico', None]",PLoS One,,,True
dd2a154b5fe59f997e47913b3a6da5d23bdb7556,PMC,Resveratrol enhances HBV replication through activating Sirt1-PGC-1α-PPARα pathway,http://dx.doi.org/10.1038/srep24744,PMC4838842,27098390,CC BY,"The population of hepatitis B combined with a number of metabolic disorders is increasing significantly. Resveratrol (RSV) has been used as a preclinical drug for the treatment of the metabolic disorders. However, the impact of RSV on HBV replication remains unknown. In this study, the HBV-expressing hepatocelluar carcinoma cell line and mouse model created by hydrodynamic injection of viral DNA were used. We found that RSV activates Sirt1, which in turn deacetylates PGC-1α and subsequently increases the transcriptional activity of PPARα, leading to the enhanced HBV transcription and replication in vitro and in vivo. In addition, we found that this pathway is also required for fasting-induced HBV transcription. Taken together, this study identifies that RSV enhances HBV transcription and replication especially acting on the core promoter, which depends on Sirt1-PGC-1α-PPARα pathway. We conclude that RSV may exacerbate the progression of hepatitis B and that patients with hepatitis B infection should be cautious taking RSV as a dietary supplement.",2016 Apr 21,"['Shi, Yixian', 'Li, Yongjun', 'Huang, Chenjie', 'Ying, Lixiong', 'Xue, Jihua', 'Wu, Haicong', 'Chen, Zhi', 'Yang, Zhenggang']",Sci Rep,,,True
7a7c1c991ee3905b06ca628a523f693a402cc7f1,PMC,Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia,http://dx.doi.org/10.1186/s12879-016-1492-4,PMC4839124,27097824,CC BY,"BACKGROUND: Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) is a poorly understood disease with no known treatments. We describe the clinical features and treatment outcomes of patients with laboratory confirmed MERS-CoV at a regional referral center in the Kingdom of Saudi Arabia. METHODS: In 2014, a retrospective chart review was performed on patients with a laboratory confirmed diagnosis of MERS-CoV to determine clinical and treatment characteristics associated with death. Confounding was evaluated and a multivariate logistic regression was performed to assess the independent effect of treatments administered. RESULTS: Fifty-one patients had an overall mortality of 37 %. Most patients were male (78 %) with a mean age of 54 years. Almost a quarter of the patients were healthcare workers (23.5 %) and 41 % had a known exposure to another person with MERS-CoV. Survival was associated with male gender, working as a healthcare worker, history of hypertension, vomiting on admission, elevated respiratory rate, abnormal lung exam, elevated alanine transaminase (ALT), clearance of MERS-CoV on repeat PCR polymerase chain reaction (PCR) testing, and mycophenolate mofetil treatment. Survival was reduced in the presence of coronary artery disease, hypotension, hypoxemia, CXR (chest X-ray) abnormalities, leukocytosis, creatinine >1 · 5 mg/dL, thrombocytopenia, anemia, and renal failure. In a multivariate analysis of treatments administered, severity of illness was the greatest predictor of reduced survival. CONCLUSIONS: Care for patients with MERS-CoV remains a challenge. In this retrospective cohort, interferon beta and mycophenolate mofetil treatment were predictors of increased survival in the univariate analysis. Severity of illness was the greatest predictor of reduced survival in the multivariate analysis. Larger randomized trials are needed to better evaluate the efficacy of these treatment regimens for MERS-CoV.",2016 Apr 21,"['Al Ghamdi, Mohammed', 'Alghamdi, Khalid M.', 'Ghandoora, Yasmeen', 'Alzahrani, Ameera', 'Salah, Fatmah', 'Alsulami, Abdulmoatani', 'Bawayan, Mayada F.', 'Vaidya, Dhananjay', 'Perl, Trish M.', 'Sood, Geeta']",BMC Infect Dis,,,True
9bacd5e08a587ec2c4a6f367044249fa7c0129bd,PMC,HTS-Driven Discovery of New Chemotypes with West Nile Virus Inhibitory Activity,http://dx.doi.org/10.3390/molecules15031690,PMC4839297,20336008,CC BY,"West Nile virus (WNV) is a positive sense, single-stranded RNA virus that can cause illness in humans when transmitted via mosquito vectors. Unfortunately, no antivirals or vaccines are currently available, and therefore efficient and safe antivirals are urgently needed. We developed a high throughput screen to discover small molecule probes that inhibit virus infection of Vero E6 cells. A primary screen of a 13,001 compound library at a 10 μM final concentration was conducted using the 384-well format. Z′ values ranged from 0.54–0.83 with a median of 0.74. Average S/B was 17 and S/N for each plate ranged from 10.8 to 23.9. Twenty-six compounds showed a dose response in the HT screen and were further evaluated in a time of addition assay and in a titer reduction assay. Seven compounds showed potential as small molecule probes directed at WNV. The hit rate from the primary screen was 0.185% (24 compounds out of 13,001 compounds) and from the secondary screens was 0.053% (7 out of 13,001 compounds) respectively.",2010 Mar 12,"['Chung, Dong Hoon', 'Jonsson, Colleen B.', 'Maddox, Clinton', 'McKellip, Sara N.', 'Moore, Blake. P.', 'Heil, Marintha', 'White, E. Lucile', 'Ananthan, Subramaniam', 'Li, Qianjun', 'Feng, Shuang', 'Rasmussen, Lynn']",Molecules,,,True
0257e6797e12beb91a4a4fcd7130f90d84260718,PMC,Integrated sequence and immunology filovirus database at Los Alamos,http://dx.doi.org/10.1093/database/baw047,PMC4839628,27103629,CC BY,"The Ebola outbreak of 2013–15 infected more than 28 000 people and claimed more lives than all previous filovirus outbreaks combined. Governmental agencies, clinical teams, and the world scientific community pulled together in a multifaceted response ranging from prevention and disease control, to evaluating vaccines and therapeutics in human trials. As this epidemic is finally coming to a close, refocusing on long-term prevention strategies becomes paramount. Given the very real threat of future filovirus outbreaks, and the inherent uncertainty of the next outbreak virus and geographic location, it is prudent to consider the extent and implications of known natural diversity in advancing vaccines and therapeutic approaches. To facilitate such consideration, we have updated and enhanced the content of the filovirus portion of Los Alamos Hemorrhagic Fever Viruses Database. We have integrated and performed baseline analysis of all family Filoviridae sequences deposited into GenBank, with associated immune response data, and metadata, and we have added new computational tools with web-interfaces to assist users with analysis. Here, we (i) describe the main features of updated database, (ii) provide integrated views and some basic analyses summarizing evolutionary patterns as they relate to geo-temporal data captured in the database and (iii) highlight the most conserved regions in the proteome that may be useful for a T cell vaccine strategy. Database URL: www.hfv.lanl.gov",2016 Apr 21,"['Yusim, Karina', 'Yoon, Hyejin', 'Foley, Brian', 'Feng, Shihai', 'Macke, Jennifer', 'Dimitrijevic, Mira', 'Abfalterer, Werner', 'Szinger, James', 'Fischer, Will', 'Kuiken, Carla', 'Korber, Bette']",Database (Oxford),,,True
46ebfbb3db79bab7f78361721e37e8b35a34037e,PMC,Solvent/Detergent Virally Inactivated Serum Eye Drops Restore Healthy Ocular Epithelium in a Rabbit Model of Dry-Eye Syndrome,http://dx.doi.org/10.1371/journal.pone.0153573,PMC4839776,27100624,CC BY,"Application of autologous serum eye drops (SEDs) is a recognized means to treat severe dry-eye syndrome (DES). Due to the inconvenience and difficulty of preparing SEDs from some patients, producing SEDs from allogeneic blood donations is gaining popularity. A major safety concern associated with allogeneic blood is virus transmission. We therefore herein evaluated the possibility of applying a solvent/detergent (S/D) treatment to inactivate viruses and studied the impacts of such treatment of SEDs to resolve DES in a rabbit model. Sera prepared from the blood of five rabbits were pooled and divided into two sub-pools. One was untreated (SEDs), while the other was virally-inactivated with 1% Tri-n-butyl phosphate/1% Triton X-45 at 31°C for 1 h (S/D-SEDs). DES was induced in rabbits using 0.1% benzalkonium chloride (BAC). Rabbits were divided into five groups of two rabbits each. One group was untreated (control), three were treated twice daily for 3 weeks using PBS, SEDs, or S/D-SEDs, and the last received an additional 0.1% BAC (as the negative control). The DES condition was determined by measuring aqueous tear secretion (Schirmer’s test), corneal fluorescein staining, a corneal histologic examination, TUNEL stain apoptosis, and corneal inflammatory marker (tumor necrosis factor-α, interleukin (IL)-1β, IL-8, and IL-6) expressions. We first confirmed that SEDs and S/D-SEDs had similar protein profiles and transforming growth factor (TGF)-β contents. Animal experiments showed that tear secretion did not significantly differ between the SED and S/D-SED groups but was significantly higher than in the PBS group. Eye fluorescein staining revealed dramatic improvements in epithelial defects in groups treated with SEDs or S/D-SEDs, and hematoxylin/eosin staining revealed microscopic epithelial layers similar to those of the untreated controls. Inflammatory markers and TUNEL studies showed that healthy epithelium had been restored in groups treated with SEDs or S/D-SEDs. In conclusion, this preclinical study supports the possibility of using S/D virally inactivated SEDs to treat DES and restore a normal epithelium.",2016 Apr 21,"['Tseng, Ching-Li', 'Chen, Zhi-Yu', 'Renn, Ting-Yi', 'Hsiao, Shun-Hung', 'Burnouf, Thierry']",PLoS One,,,True
2a3a68a67776a01043a6a156b69be803c7118a6d,PMC,The Vpu-interacting Protein SGTA Regulates Expression of a Non-glycosylated Tetherin Species,http://dx.doi.org/10.1038/srep24934,PMC4840321,27103333,CC BY,"The HIV-1 accessory protein Vpu enhances virus release by counteracting the host restriction factor tetherin. To further understand the role of host cell proteins in Vpu function, we carried out yeast two-hybrid screening and identified a previously reported Vpu-interacting host factor, small glutamine-rich tetratricopeptide repeat-containing protein (SGTA). While RNAi-mediated depletion of SGTA did not significantly affect levels of tetherin or virus release efficiency, we observed that overexpression of SGTA inhibited HIV-1 release in a Vpu- and tetherin-independent manner. Overexpression of SGTA in the presence of Vpu, but not in its absence, resulted in a marked stabilization and cytosolic relocalization of a 23-kDa, non-glycosylated tetherin species. Coimmunoprecipitation studies indicated that non-glycosylated tetherin is stabilized through the formation of a ternary SGTA/Vpu/tetherin complex. This accumulation of non-glycosylated tetherin is due to inhibition of its degradation, independent of the ER-associated degradation (ERAD) pathway. Because the SGTA-stabilized tetherin species is partially localized to the cytosol, we propose that overexpression of SGTA in the presence of Vpu blocks the translocation of tetherin across the ER membrane, resulting in cytosolic accumulation of a non-glycosylated tetherin species. Although our results do not provide support for a physiological function of SGTA in HIV-1 replication, they demonstrate that SGTA overexpression regulates tetherin expression and stability, thus providing insights into the function of SGTA in ER translocation and protein degradation.",2016 Apr 22,"['Waheed, Abdul A.', 'MacDonald, Scott', 'Khan, Maisha', 'Mounts, Megan', 'Swiderski, Maya', 'Xu, Yue', 'Ye, Yihong', 'Freed, Eric O.']",Sci Rep,,,True
374da1c5f22a3b6acbea8b991d861026d4620042,PMC,The Vpu-interacting Protein SGTA Regulates Expression of a Non-glycosylated Tetherin Species,http://dx.doi.org/10.1038/srep24934,PMC4840321,27103333,CC BY,"The HIV-1 accessory protein Vpu enhances virus release by counteracting the host restriction factor tetherin. To further understand the role of host cell proteins in Vpu function, we carried out yeast two-hybrid screening and identified a previously reported Vpu-interacting host factor, small glutamine-rich tetratricopeptide repeat-containing protein (SGTA). While RNAi-mediated depletion of SGTA did not significantly affect levels of tetherin or virus release efficiency, we observed that overexpression of SGTA inhibited HIV-1 release in a Vpu- and tetherin-independent manner. Overexpression of SGTA in the presence of Vpu, but not in its absence, resulted in a marked stabilization and cytosolic relocalization of a 23-kDa, non-glycosylated tetherin species. Coimmunoprecipitation studies indicated that non-glycosylated tetherin is stabilized through the formation of a ternary SGTA/Vpu/tetherin complex. This accumulation of non-glycosylated tetherin is due to inhibition of its degradation, independent of the ER-associated degradation (ERAD) pathway. Because the SGTA-stabilized tetherin species is partially localized to the cytosol, we propose that overexpression of SGTA in the presence of Vpu blocks the translocation of tetherin across the ER membrane, resulting in cytosolic accumulation of a non-glycosylated tetherin species. Although our results do not provide support for a physiological function of SGTA in HIV-1 replication, they demonstrate that SGTA overexpression regulates tetherin expression and stability, thus providing insights into the function of SGTA in ER translocation and protein degradation.",2016 Apr 22,"['Waheed, Abdul A.', 'MacDonald, Scott', 'Khan, Maisha', 'Mounts, Megan', 'Swiderski, Maya', 'Xu, Yue', 'Ye, Yihong', 'Freed, Eric O.']",Sci Rep,,,False
9c5447c495379f968aacd114e73a03039ccfd69d,PMC,Epidemic strain YC2014 of porcine epidemic diarrhea virus could provide piglets against homologous challenge,http://dx.doi.org/10.1186/s12985-016-0529-z,PMC4840883,27103490,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is the main causative agent of porcine epidemic diarrhea (PED). Since December 2010, a large-scale outbreak of diarrhea has been observed in swine farms in China. Accumulated evidence indicates that this large-scale outbreak of diarrhea were caused by highly virulent PEDV variants. METHODS: A PEDV strain, YC2014, was isolated from intestinal samples of suckling piglets with acute diarrhea in 2014. The complete genomic sequence of YC2014 and the nucleotide sequence of S gene were aligned with sequences of published isolates using MEGA 5.1 software. The immune protective efficiency of YC2014 were determined by testing PEDV neutralizing antibodies in sera, the colostrum and the milk on 7th day after farrowing of the immunized sows. The diarrhea symptoms of piglets after challenge were also observed. RESULTS: Phylogenetic analysis of the complete genomic sequence of YC2014 and the nucleotide sequence of S gene demonstrated that the YC2014 PEDV strain was clustered with the PEDV epidemic strains, with >99 % nucleotide identity to these PEDV strains. The S gene sequence of YC2014 shared only 93.9 % ~ 94.4 % identities with classical CV777, DR13 and JS2008 strains, with 15 nucleotide insertion in three sites and three nucleotide deletion in one site. The amino acid (AA) sequence of S gene of YC2014 shared only 92.8 % ~ 93.4 % identities with classical CV777, DR13 and JS2008 strains, with 5 AA insertion in two sites and 1 AA deletion in one site. In the immune protective efficiency tests, the neutralizing antibody titers in sera, the colostrum and the milk on 7th day after farrowing of the inactivated YC2014 PEDV strain immunized group were significantly higher than the inactivated CV777 immunized group and the inactivated DR13 immunized group (P < 0.05). The traditional inactivated PEDV vaccines made from CV777 or DR13 could not protect piglets from YC2014 challenge, while inactivated YC2014 could provide piglets with 100 % protection against YC2014 challenge. CONCLUSIONS: The results showed that, great antigenicity variation had occurred to this YC2014 PEDV strain. The YC2014 PEDV strain could provide piglets against homologous challenge. It is critical for future pathogenic and antigenic studies, as well as for the development of effective preventive and control vaccines against PEDV.",2016 Apr 22,"['Lin, Huixing', 'Chen, Lei', 'Gao, Lu', 'Yuan, Xiaomin', 'Ma, Zhe', 'Fan, Hongjie']",Virol J,,,True
f42073cb33dc2aa926898dd2ab05da828f8e7790,PMC,Open drug discovery for the Zika virus,http://dx.doi.org/10.12688/f1000research.8013.1,PMC4841202,27134728,CC BY,"The Zika virus (ZIKV) outbreak in the Americas has caused global concern that we may be on the brink of a healthcare crisis. The lack of research on ZIKV in the over 60 years that we have known about it has left us with little in the way of starting points for drug discovery. Our response can build on previous efforts with virus outbreaks and lean heavily on work done on other flaviviruses such as dengue virus. We provide some suggestions of what might be possible and propose an open drug discovery effort that mobilizes global science efforts and provides leadership, which thus far has been lacking. We also provide a listing of potential resources and molecules that could be prioritized for testing as in vitro assays for ZIKV are developed. We propose also that in order to incentivize drug discovery, a neglected disease priority review voucher should be available to those who successfully develop an FDA approved treatment. Learning from the response to the ZIKV, the approaches to drug discovery used and the success and failures will be critical for future infectious disease outbreaks.",2016 Feb 9,"['Ekins, Sean', 'Mietchen, Daniel', 'Coffee, Megan', 'Stratton, Thomas P', 'Freundlich, Joel S', 'Freitas-Junior, Lucio', 'Muratov, Eugene', 'Siqueira-Neto, Jair', 'Williams, Antony J', 'Andrade, Carolina']",F1000Res,,,True
60b69719c85b64d84bb0b4621ed53108914aebe8,PMC,"Pathogenicity of Genetically Similar, H5N1 Highly Pathogenic Avian Influenza Virus Strains in Chicken and the Differences in Sensitivity among Different Chicken Breeds",http://dx.doi.org/10.1371/journal.pone.0153649,PMC4841636,27078641,CC BY,"Differences in the pathogenicity of genetically closely related H5N1 highly pathogenic avian influenza viruses (HPAIVs) were evaluated in White Leghorn chickens. These viruses varied in the clinical symptoms they induced, including lethality, virus shedding, and replication in host tissues. A comparison of the host responses in the lung, brain, and spleen suggested that the differences in viral replication efficiency were related to the host cytokine response at the early phase of infection, especially variations in the proinflammatory cytokine IL-6. Based on these findings, we inoculated the virus that showed the mildest pathogenicity among the five tested, A/pigeon/Thailand/VSMU-7-NPT/2004, into four breeds of Thai indigenous chicken, Phadu-Hung-Dang (PHD), Chee, Dang, and Luang-Hung-Khao (LHK), to explore effects of genetic background on host response. Among these breeds, Chee, Dang, and LHK showed significantly longer survival times than White Leghorns. Virus shedding from dead Thai indigenous chickens was significantly lower than that from White Leghorns. Although polymorphisms were observed in the Mx and MHC class I genes, there was no significant association between the polymorphisms in these loci and resistance to HPAIV.",2016 Apr 14,"['Matsuu, Aya', 'Kobayashi, Tomoko', 'Patchimasiri, Tuangthong', 'Shiina, Takashi', 'Suzuki, Shingo', 'Chaichoune, Kridsada', 'Ratanakorn, Parntep', 'Hiromoto, Yasuaki', 'Abe, Haruka', 'Parchariyanon, Sujira', 'Saito, Takehiko']",PLoS One,,,True
ad3b8061a983745471ac96a30d534b00f57a9ffb,PMC,Comparative analysis of viral RNA signatures on different RIG-I-like receptors,http://dx.doi.org/10.7554/eLife.11275,PMC4841775,27011352,CC BY,"The RIG-I-like receptors (RLRs) play a major role in sensing RNA virus infection to initiate and modulate antiviral immunity. They interact with particular viral RNAs, most of them being still unknown. To decipher the viral RNA signature on RLRs during viral infection, we tagged RLRs (RIG-I, MDA5, LGP2) and applied tagged protein affinity purification followed by next-generation sequencing (NGS) of associated RNA molecules. Two viruses with negative- and positive-sense RNA genome were used: measles (MV) and chikungunya (CHIKV). NGS analysis revealed that distinct regions of MV genome were specifically recognized by distinct RLRs: RIG-I recognized defective interfering genomes, whereas MDA5 and LGP2 specifically bound MV nucleoprotein-coding region. During CHIKV infection, RIG-I associated specifically to the 3’ untranslated region of viral genome. This study provides the first comparative view of the viral RNA ligands for RIG-I, MDA5 and LGP2 in the presence of infection. DOI: http://dx.doi.org/10.7554/eLife.11275.001",,"['Sanchez David, Raul Y', 'Combredet, Chantal', 'Sismeiro, Odile', 'Dillies, Marie-Agnès', 'Jagla, Bernd', 'Coppée, Jean-Yves', 'Mura, Marie', 'Guerbois Galla, Mathilde', 'Despres, Philippe', 'Tangy, Frédéric', 'Komarova, Anastassia V']",eLife.; 5:e11275,,,True
3619c9e99ff6ceb2fa038d13239e6fce4e818995,PMC,Comparison of SYBR green I real-time RT-PCR with conventional agarose gel-based RT-PCR for the diagnosis of infectious bronchitis virus infection in chickens in Morocco,http://dx.doi.org/10.1186/s13104-016-2037-z,PMC4841946,27106608,CC BY,"BACKGROUND: A rapid, sensitive, and specific molecular method for the diagnosis of infectious bronchitis virus (IBV) infection is important in curbing infectious bronchitis outbreaks in Morocco and other countries. METHODS: In this study, an easy-to-perform SYBR green I real-time reverse transcriptase polymerase chain reaction (RT-PCR) targeting the nucleocapsid gene of IBV was developed and compared with conventional agarose gel-based RT-PCR for the detection of IBV infection. RESULTS: We found that the SYBR green I real-time RT-PCR was at least 10 times more sensitive than the agarose gel electrophoresis detection method. The assay exhibited high specificity for IBV infection. All negative controls, such as Newcastle disease virus, infectious bursal disease virus, and avian influenza virus, were not detected. CONCLUSION: The SYBR green I real-time RT-PCR test described herein can be used to rapidly distinguish IBV from other respiratory pathogens, which is important for diagnosis and control of infectious bronchitis outbreaks in Morocco. The test is a valuable and useful method as a routine assay for diagnosis of clinical IBV infection in commercial chickens.",2016 Apr 22,"['Fellahi, Siham', 'Harrak, Mehdi El', 'Kuhn, Jens H.', 'Sebbar, Ghizlane', 'Bouaiti, El Arbi', 'Khataby, Khadija', 'Fihri, Ouafae Fassi', 'Houadfi, Mohammed El', 'Ennaji, My Mustapha']",BMC Res Notes,,,True
27dfdf0c086653e07dbc5d50ed1d2bc9228cfca8,PMC,Correction: Middle East Respiratory Syndrome Coronavirus Intra-Host Populations Are Characterized by Numerous High Frequency Variants,http://dx.doi.org/10.1371/journal.pone.0154424,PMC4844146,27111439,CC BY,,2016 Apr 25,"['Borucki, Monica K.', 'Lao, Victoria', 'Hwang, Mona', 'Gardner, Shea', 'Adney, Danielle', 'Munster, Vincent', 'Bowen, Richard', 'Allen, Jonathan E.']",PLoS One,,,False
e1f84229bcacd4ea32af6127963a174f888acb09,PMC,Identification of critical residues in Hepatitis E virus macro domain involved in its interaction with viral methyltransferase and ORF3 proteins,http://dx.doi.org/10.1038/srep25133,PMC4844956,27113483,CC BY,"Hepatitis E virus (HEV) is a major cause of hepatitis in normal and organ transplant individuals. HEV open reading frame-1 encodes a polypeptide comprising of the viral nonstructural proteins as well as domains of unknown function such as the macro domain (X-domain), V, DUF3729 and Y. The macro domain proteins are ubiquitously present from prokaryotes to human and in many positive-strand RNA viruses, playing important roles in multiple cellular processes. Towards understanding the function of the HEV macro domain, we characterized its interaction partners among other HEV encoded proteins. Here, we report that the HEV X-domain directly interacts with the viral methyltransferase and the ORF3 proteins. ORF3 association with the X-domain was mediated through two independent motifs, located within its N-terminal 35aa (amino acids) and C-terminal 63-123aa. Methyltransferase interaction domain was mapped to N-terminal 30-90aa. The X-domain interacted with both ORF3 and methyltransferase through its C-terminal region, involving 66(th),67(th) isoleucine and 101(st),102(nd) leucine, conserved across HEV genotypes. Furthermore, ORF3 and methyltransferase competed with each other for associating with the X-domain. These findings provide molecular understanding of the interaction between the HEV macro domain, methyltransferase and ORF3, suggesting an important role of the macro domain in the life cycle of HEV.",2016 Apr 26,"['Anang, Saumya', 'Subramani, Chandru', 'Nair, Vidya P.', 'Kaul, Sheetal', 'Kaushik, Nidhi', 'Sharma, Chandresh', 'Tiwari, Ashutosh', 'Ranjith-Kumar, CT', 'Surjit, Milan']",Sci Rep,,,True
2ccbb7b5eeb50c2d41a71500cd920a614a402a0e,PMC,Identification of critical residues in Hepatitis E virus macro domain involved in its interaction with viral methyltransferase and ORF3 proteins,http://dx.doi.org/10.1038/srep25133,PMC4844956,27113483,CC BY,"Hepatitis E virus (HEV) is a major cause of hepatitis in normal and organ transplant individuals. HEV open reading frame-1 encodes a polypeptide comprising of the viral nonstructural proteins as well as domains of unknown function such as the macro domain (X-domain), V, DUF3729 and Y. The macro domain proteins are ubiquitously present from prokaryotes to human and in many positive-strand RNA viruses, playing important roles in multiple cellular processes. Towards understanding the function of the HEV macro domain, we characterized its interaction partners among other HEV encoded proteins. Here, we report that the HEV X-domain directly interacts with the viral methyltransferase and the ORF3 proteins. ORF3 association with the X-domain was mediated through two independent motifs, located within its N-terminal 35aa (amino acids) and C-terminal 63-123aa. Methyltransferase interaction domain was mapped to N-terminal 30-90aa. The X-domain interacted with both ORF3 and methyltransferase through its C-terminal region, involving 66(th),67(th) isoleucine and 101(st),102(nd) leucine, conserved across HEV genotypes. Furthermore, ORF3 and methyltransferase competed with each other for associating with the X-domain. These findings provide molecular understanding of the interaction between the HEV macro domain, methyltransferase and ORF3, suggesting an important role of the macro domain in the life cycle of HEV.",2016 Apr 26,"['Anang, Saumya', 'Subramani, Chandru', 'Nair, Vidya P.', 'Kaul, Sheetal', 'Kaushik, Nidhi', 'Sharma, Chandresh', 'Tiwari, Ashutosh', 'Ranjith-Kumar, CT', 'Surjit, Milan']",Sci Rep,,,False
7e4299dd78b35e5223c34355cd13c9c99ed72c25,PMC,Divergent bufavirus harboured in megabats represents a new lineage of parvoviruses,http://dx.doi.org/10.1038/srep24257,PMC4845017,27113297,CC BY,"Bufavirus is a recently recognized member of the genus Protoparvovirus in the subfamily Parvovirinae. It has been reported that human bufavirus was detected predominantly in patients with diarrhoea in several countries. However, little is known about bufavirus or its close relatives in nonhuman mammals. In this study, we performed nested-PCR screening and identified bufavirus from 12 megabats of Pteropus spp. in Indonesia. Furthermore, we determined nearly the full genome sequence of a novel megabat-borne bufavirus, tentatively named megabat bufavirus 1. Phylogenetic analyses showed that megabat bufavirus 1 clustered with known protoparvoviruses, including human bufavirus but represented a distinct lineage of bufavirus. Our analyses also inferred phylogenetic relationships among animal-borne bufaviruses recently reported by other studies. Recombination analyses suggested that the most common recent ancestor of megabat bufavirus 1 might have arisen from multiple genetic recombination events. These results characterized megabat bufavirus 1 as the first protoparvovirus discovered from megabats and indicates the high genetic divergence of bufavirus.",2016 Apr 26,"['Sasaki, Michihito', 'Gonzalez, Gabriel', 'Wada, Yuji', 'Setiyono, Agus', 'Handharyani, Ekowati', 'Rahmadani, Ibenu', 'Taha, Siswatiana', 'Adiani, Sri', 'Latief, Munira', 'Kholilullah, Zainal Abidin', 'Subangkit, Mawar', 'Kobayashi, Shintaro', 'Nakamura, Ichiro', 'Kimura, Takashi', 'Orba, Yasuko', 'Ito, Kimihito', 'Sawa, Hirofumi']",Sci Rep,,,True
80850d03f16060e460bd50e5622e2196c0622f54,PMC,A web-based resource for designing therapeutics against Ebola Virus,http://dx.doi.org/10.1038/srep24782,PMC4845023,27113850,CC BY,"In this study, we describe a web-based resource, developed for assisting the scientific community in designing an effective therapeutics against the Ebola virus. Firstly, we predicted and identified experimentally validated epitopes in each of the antigens/proteins of the five known ebolaviruses. Secondly, we generated all the possible overlapping 9mer peptides from the proteins of ebolaviruses. Thirdly, conserved peptides across all the five ebolaviruses (four human pathogenic species) with no identical sequence in the human proteome, based on 1000 Genomes project, were identified. Finally, we identified peptide or epitope-based vaccine candidates that could activate both the B- and T-cell arms of the immune system. In addition, we also identified efficacious siRNAs against the mRNA transcriptome (absent in human transcriptome) of all the five ebolaviruses. It was observed that three species can potentially be targeted by a single siRNA (19mer) and 75 siRNAs can potentially target at least two species. A web server, EbolaVCR, has been developed that incorporates all the above information and useful computational tools (http://crdd.osdd.net/oscadd/ebola/).",2016 Apr 26,"['Dhanda, Sandeep Kumar', 'Chaudhary, Kumardeep', 'Gupta, Sudheer', 'Brahmachari, Samir Kumar', 'Raghava, Gajendra P. S.']",Sci Rep,,,True
8e47f269f449983eb0dc70d257f09f27b1e81247,PMC,Antiviral Role of IFITM Proteins in African Swine Fever Virus Infection,http://dx.doi.org/10.1371/journal.pone.0154366,PMC4846163,27116236,CC BY,"The interferon-induced transmembrane (IFITM) protein family is a group of antiviral restriction factors that impair flexibility and inhibit membrane fusion at the plasma or the endosomal membrane, restricting viral progression at entry. While IFITMs are widely known to inhibit several single-stranded RNA viruses, there are limited reports available regarding their effect in double-stranded DNA viruses. In this work, we have analyzed a possible antiviral function of IFITMs against a double stranded DNA virus, the African swine fever virus (ASFV). Infection with cell-adapted ASFV isolate Ba71V is IFN sensitive and it induces IFITMs expression. Interestingly, high levels of IFITMs caused a collapse of the endosomal pathway to the perinuclear area. Given that ASFV entry is strongly dependent on endocytosis, we investigated whether IFITM expression could impair viral infection. Expression of IFITM1, 2 and 3 reduced virus infectivity in Vero cells, with IFITM2 and IFITM3 having an impact on viral entry/uncoating. The role of IFITM2 in the inhibition of ASFV in Vero cells could be related to impaired endocytosis-mediated viral entry and alterations in the cholesterol efflux, suggesting that IFITM2 is acting at the late endosome, preventing the decapsidation stage of ASFV.",2016 Apr 26,"['Muñoz-Moreno, Raquel', 'Cuesta-Geijo, Miguel Ángel', 'Martínez-Romero, Carles', 'Barrado-Gil, Lucía', 'Galindo, Inmaculada', 'García-Sastre, Adolfo', 'Alonso, Covadonga']",PLoS One,,,True
e2904c6e462291682dc4d65ce47a91bdc8509747,PMC,Identification of miRNomes reveals ssc-miR-30d-R_1 as a potential therapeutic target for PRRS viral infection,http://dx.doi.org/10.1038/srep24854,PMC4846818,27117627,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) is known to cause reproductive disorders, such as abortion, in pregnant sows as well as immunosuppressive respiratory complications, leading to severe respiratory tract infections in young pigs. In this study, an in-depth analysis of the miRNomes in mock- and virus-infected pig lungs was carried out. We found that highly expressed ssc-miR-30d-R_1 was decreased in infected lungs, and reduced levels were significantly correlated with infection by PRRSV. Moreover, ssc-miR-30d-R_1 was shown to target Toll-like receptor 4 (TLR4) and to suppress the production of immune cytokines through inhibition of the TLR4/MyD88/NF-κB pathway. ssc-miR-30d-R_1 significantly reduced viral infections and pathological changes in pig lungs in vivo. Our current study reveals the miRNomes of PRRSV-infected pig lungs and indicates that ssc-miR-30d-R_1 is potential therapeutic agent for controlling PRRSV infection.",2016 Apr 27,"['Wang, Chengmin', 'Zhang, Yanyu', 'Luo, Jing', 'Ding, Hua', 'Liu, Shelan', 'Amer, Said', 'Xie, Li', 'Lyv, Wenting', 'Su, Wen', 'Li, Meng', 'Sun, Qinmiao', 'Dai, Jiayin', 'He, Hongxuan']",Sci Rep,,,True
b98e584fe5f4e0d10462c8475bd596fc004de57c,PMC,Identification of miRNomes reveals ssc-miR-30d-R_1 as a potential therapeutic target for PRRS viral infection,http://dx.doi.org/10.1038/srep24854,PMC4846818,27117627,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) is known to cause reproductive disorders, such as abortion, in pregnant sows as well as immunosuppressive respiratory complications, leading to severe respiratory tract infections in young pigs. In this study, an in-depth analysis of the miRNomes in mock- and virus-infected pig lungs was carried out. We found that highly expressed ssc-miR-30d-R_1 was decreased in infected lungs, and reduced levels were significantly correlated with infection by PRRSV. Moreover, ssc-miR-30d-R_1 was shown to target Toll-like receptor 4 (TLR4) and to suppress the production of immune cytokines through inhibition of the TLR4/MyD88/NF-κB pathway. ssc-miR-30d-R_1 significantly reduced viral infections and pathological changes in pig lungs in vivo. Our current study reveals the miRNomes of PRRSV-infected pig lungs and indicates that ssc-miR-30d-R_1 is potential therapeutic agent for controlling PRRSV infection.",2016 Apr 27,"['Wang, Chengmin', 'Zhang, Yanyu', 'Luo, Jing', 'Ding, Hua', 'Liu, Shelan', 'Amer, Said', 'Xie, Li', 'Lyv, Wenting', 'Su, Wen', 'Li, Meng', 'Sun, Qinmiao', 'Dai, Jiayin', 'He, Hongxuan']",Sci Rep,,,False
465ce310d1edd953819b77c96fa57e62d8cbc042,PMC,Antiviral Activity of Graphene–Silver Nanocomposites against Non-Enveloped and Enveloped Viruses,http://dx.doi.org/10.3390/ijerph13040430,PMC4847092,27104546,CC BY,"The discovery of novel antiviral materials is important because many infectious diseases are caused by viruses. Silver nanoparticles have demonstrated strong antiviral activity, and graphene is a potential antimicrobial material due to its large surface area, high carrier mobility, and biocompatibility. No studies on the antiviral activity of nanomaterials on non-enveloped viruses have been reported. To investigate the antiviral activity of graphene oxide (GO) sheets and GO sheets with silver particles (GO-Ag) against enveloped and non-enveloped viruses, feline coronavirus (FCoV) with an envelope and infectious bursal disease virus (IBDV) without an envelope were chosen. The morphology and sizes of GO and GO-Ag were characterized by transmission, scanning electron microscopy, and X-ray diffraction. A virus inhibition assay was used to identify the antiviral activity of GO and GO-Ag. Go-Ag inhibited 25% of infection by FCoV and 23% by IBDV, whereas GO only inhibited 16% of infection by FCoV but showed no antiviral activity against the infection by IBDV. Further application of GO and GO-Ag can be considered for personal protection equipment to decrease the transmission of viruses.",2016 Apr 19,"['Chen, Yi-Ning', 'Hsueh, Yi-Huang', 'Hsieh, Chien-Te', 'Tzou, Dong-Ying', 'Chang, Pai-Ling']",Int J Environ Res Public Health,,,True
f54e577394738498bde347596b1dd5b1156d235d,PMC,Comparison of molecular detection methods for pertussis in children during a state-wide outbreak,http://dx.doi.org/10.1186/s12941-016-0142-4,PMC4847268,27121506,CC BY,"A state-wide pertussis outbreak occurred in Washington during the winter–spring months of 2012, concurrent with respiratory viral season. We compared performance characteristics of a laboratory-developed pertussis PCR (LD-PCR for Bordetella pertussis, Bordetella parapertussis, and Bordetella holmesii) and rapid multiplex PCR (RM-PCR) for respiratory viruses (FilmArray™, BioFire, B. pertussis data unblinded following FDA approval post outbreak). We analyzed three cohorts of patients using physician testing orders as a proxy for clinical suspicion for pertussis or respiratory viruses: Cohort 1, tested by LD-PCR for pertussis pathogens only by nasopharyngeal swab; Cohort 2, by RM-PCR for respiratory viruses only by mid-nasal turbinate swab; and Cohort 3, by both methods. B. pertussis was detected in a total of 25 of the 490 patients in Cohort 3 in which LD-PCR detected 20/25 (80 %) cases and the RM-PCR detected 24/25 (96 %; p = 0.2). Pertussis pathogens were detected in 21/584 (3.6 %) of samples from Cohort 1 where clinicians had a relatively strong suspicion for pertussis. In contrast, B. pertussis was detected in only 4/3071 (0.1 %) specimens from Cohort 2 where suspicion for pertussis was lower (p < 0.001 for comparison with Cohort 1). In summary, the two laboratory methods were comparable for the detection of B. pertussis.",2016 Apr 27,"['Qin, X.', 'Zerr, D. M.', 'Kronman, M. P.', 'Adler, A. L.', 'Berry, J. E.', 'Rich, S.', 'Buccat, A. M.', 'Xu, M.', 'Englund, J. A.']",Ann Clin Microbiol Antimicrob,,,True
0180abece22ace6548f4601591c98059808d0509,PMC,Enterovirus D68 Infections Associated with Severe Respiratory Illness in Elderly Patients and Emergence of a Novel Clade in Hong Kong,http://dx.doi.org/10.1038/srep25147,PMC4848506,27121085,CC BY,"Despite the recent emergence of enterovirus D68 (EV-D68), its clinical impact on adult population is less well defined. To better define the epidemiology of EV-D68, 6,800 nasopharyngeal aspirates (NPAs) from 2010–2014 were subject to EV-D68 detection by RT-PCR and sequencing of 5′UTR and partial VP1. EV-D68 was detected in 30 (0.44%) NPAs from 22 children and 8 adults/elderlies. Sixteen patients (including five elderly) (53%) had pneumonia and 13 (43%) patients were complicated by small airway disease exacerbation. Phylogenetic analysis of VP1, 2C and 3D regions showed four distinct lineages of EV-D68, clade A1, A2, B1 and B3, with adults/elderlies exclusively infected by clade A2. The potentially new clade, B3, has emerged in 2014, while strains closely related to recently emerged B1 strains in the United States were also detected as early as 2011 in Hong Kong. The four lineages possessed distinct aa sequence patterns in BC and DE loops. Amino acid residues 97 and 140, within BC and DE-surface loops of VP1 respectively, were under potential positive selection. EV-D68 infections in Hong Kong usually peak in spring/summer, though with a delayed autumn/winter peak in 2011. This report suggests that EV-D68 may cause severe respiratory illness in adults/elderlies with underlying co-morbidities.",2016 Apr 28,"['Lau, Susanna K. P.', 'Yip, Cyril C. Y.', 'Zhao, Pyrear Su-Hui', 'Chow, Wang-Ngai', 'To, Kelvin K. W.', 'Wu, Alan K. L.', 'Yuen, Kwok-Yung', 'Woo, Patrick C. Y.']",Sci Rep,,,True
c5c285ad0c47bd3d84e5086846f474479a545da2,PMC,Enterovirus D68 Infections Associated with Severe Respiratory Illness in Elderly Patients and Emergence of a Novel Clade in Hong Kong,http://dx.doi.org/10.1038/srep25147,PMC4848506,27121085,CC BY,"Despite the recent emergence of enterovirus D68 (EV-D68), its clinical impact on adult population is less well defined. To better define the epidemiology of EV-D68, 6,800 nasopharyngeal aspirates (NPAs) from 2010–2014 were subject to EV-D68 detection by RT-PCR and sequencing of 5′UTR and partial VP1. EV-D68 was detected in 30 (0.44%) NPAs from 22 children and 8 adults/elderlies. Sixteen patients (including five elderly) (53%) had pneumonia and 13 (43%) patients were complicated by small airway disease exacerbation. Phylogenetic analysis of VP1, 2C and 3D regions showed four distinct lineages of EV-D68, clade A1, A2, B1 and B3, with adults/elderlies exclusively infected by clade A2. The potentially new clade, B3, has emerged in 2014, while strains closely related to recently emerged B1 strains in the United States were also detected as early as 2011 in Hong Kong. The four lineages possessed distinct aa sequence patterns in BC and DE loops. Amino acid residues 97 and 140, within BC and DE-surface loops of VP1 respectively, were under potential positive selection. EV-D68 infections in Hong Kong usually peak in spring/summer, though with a delayed autumn/winter peak in 2011. This report suggests that EV-D68 may cause severe respiratory illness in adults/elderlies with underlying co-morbidities.",2016 Apr 28,"['Lau, Susanna K. P.', 'Yip, Cyril C. Y.', 'Zhao, Pyrear Su-Hui', 'Chow, Wang-Ngai', 'To, Kelvin K. W.', 'Wu, Alan K. L.', 'Yuen, Kwok-Yung', 'Woo, Patrick C. Y.']",Sci Rep,,,False
6695dd7f637481312d8589cbc32aa3bef1c816a4,PMC,Enterovirus Control of Translation and RNA Granule Stress Responses,http://dx.doi.org/10.3390/v8040093,PMC4848588,27043612,CC BY,"Enteroviruses such as poliovirus (PV) and coxsackievirus B3 (CVB3) have evolved several parallel strategies to regulate cellular gene expression and stress responses to ensure efficient expression of the viral genome. Enteroviruses utilize their encoded proteinases to take over the cellular translation apparatus and direct ribosomes to viral mRNAs. In addition, viral proteinases are used to control and repress the two main types of cytoplasmic RNA granules, stress granules (SGs) and processing bodies (P-bodies, PBs), which are stress-responsive dynamic structures involved in repression of gene expression. This review discusses these processes and the current understanding of the underlying mechanisms with respect to enterovirus infections. In addition, the review discusses accumulating data suggesting linkage exists between RNA granule formation and innate immune sensing and activation.",2016 Mar 30,"Lloyd, Richard E.",Viruses,,,True
1d14e19f66d1a9c36b98aa2365aab80e9845616e,PMC,Current Approaches for Diagnosis of Influenza Virus Infections in Humans,http://dx.doi.org/10.3390/v8040096,PMC4848591,27077877,CC BY,"Despite significant advancement in vaccine and virus research, influenza continues to be a major public health concern. Each year in the United States of America, influenza viruses are responsible for seasonal epidemics resulting in over 200,000 hospitalizations and 30,000–50,000 deaths. Accurate and early diagnosis of influenza viral infections are critical for rapid initiation of antiviral therapy to reduce influenza related morbidity and mortality both during seasonal epidemics and pandemics. Several different approaches are currently available for diagnosis of influenza infections in humans. These include viral isolation in cell culture, immunofluorescence assays, nucleic acid amplification tests, immunochromatography-based rapid diagnostic tests, etc. Newer diagnostic approaches are being developed to overcome the limitations associated with some of the conventional detection methods. This review discusses diagnostic approaches currently available for detection of influenza viruses in humans.",2016 Apr 12,"['Vemula, Sai Vikram', 'Zhao, Jiangqin', 'Liu, Jikun', 'Wang, Xue', 'Biswas, Santanu', 'Hewlett, Indira']",Viruses,,,True
43740caefa35d11ce1aa130cd8ca86b60442b046,PMC,Shutoff of Host Gene Expression in Influenza A Virus and Herpesviruses: Similar Mechanisms and Common Themes,http://dx.doi.org/10.3390/v8040102,PMC4848596,27092522,CC BY,"The ability to shut off host gene expression is a shared feature of many viral infections, and it is thought to promote viral replication by freeing host cell machinery and blocking immune responses. Despite the molecular differences between viruses, an emerging theme in the study of host shutoff is that divergent viruses use similar mechanisms to enact host shutoff. Moreover, even viruses that encode few proteins often have multiple mechanisms to affect host gene expression, and we are only starting to understand how these mechanisms are integrated. In this review we discuss the multiplicity of host shutoff mechanisms used by the orthomyxovirus influenza A virus and members of the alpha- and gamma-herpesvirus subfamilies. We highlight the surprising similarities in their mechanisms of host shutoff and discuss how the different mechanisms they use may play a coordinated role in gene regulation.",2016 Apr 16,"['Rivas, Hembly G.', 'Schmaling, Summer K.', 'Gaglia, Marta M.']",Viruses,,,True
dc69e220d40597887fac3851a1601408fe7bf568,PMC,Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus,http://dx.doi.org/10.3390/v8040106,PMC4848600,27110812,CC BY,"Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research.",2016 Apr 21,"['Zivcec, Marko', 'Scholte, Florine E. M.', 'Spiropoulou, Christina F.', 'Spengler, Jessica R.', 'Bergeron, Éric']",Viruses,,,True
ed47ed886ac68059ec1d579c70759578c3d766e5,PMC,Non-hydrolyzable Diubiquitin Probes Reveal Linkage-Specific Reactivity of Deubiquitylating Enzymes Mediated by S2 Pockets,http://dx.doi.org/10.1016/j.chembiol.2016.03.009,PMC4850247,27066941,CC BY,"Ubiquitin chains are important post-translational modifications that control a large number of cellular processes. Chains can be formed via different linkages, which determines the type of signal they convey. Deubiquitylating enzymes (DUBs) regulate ubiquitylation status by trimming or removing chains from attached proteins. DUBs can contain several ubiquitin-binding pockets, which confer specificity toward differently linked chains. Most tools for monitoring DUB specificity target binding pockets on opposing sides of the active site; however, some DUBs contain additional pockets. Therefore, reagents targeting additional pockets are essential to fully understand linkage specificity. We report the development of active site-directed probes and fluorogenic substrates, based on non-hydrolyzable diubiquitin, that are equipped with a C-terminal warhead or a fluorogenic activity reporter moiety. We demonstrate that various DUBs in lysates display differential reactivity toward differently linked diubiquitin probes, as exemplified by the proteasome-associated DUB USP14. In addition, OTUD2 and OTUD3 show remarkable linkage-specific reactivity with our diubiquitin-based reagents.",2016 Apr 21,"['Flierman, Dennis', 'van\xa0der\xa0Heden\xa0van\xa0Noort, Gerbrand\xa0J.', 'Ekkebus, Reggy', 'Geurink, Paul\xa0P.', 'Mevissen, Tycho\xa0E.T.', 'Hospenthal, Manuela\xa0K.', 'Komander, David', 'Ovaa, Huib']",Cell Chem Biol,,,False
e733dff32efffe3238869aa7aeea1904fe814f5b,PMC,Non-hydrolyzable Diubiquitin Probes Reveal Linkage-Specific Reactivity of Deubiquitylating Enzymes Mediated by S2 Pockets,http://dx.doi.org/10.1016/j.chembiol.2016.03.009,PMC4850247,27066941,CC BY,"Ubiquitin chains are important post-translational modifications that control a large number of cellular processes. Chains can be formed via different linkages, which determines the type of signal they convey. Deubiquitylating enzymes (DUBs) regulate ubiquitylation status by trimming or removing chains from attached proteins. DUBs can contain several ubiquitin-binding pockets, which confer specificity toward differently linked chains. Most tools for monitoring DUB specificity target binding pockets on opposing sides of the active site; however, some DUBs contain additional pockets. Therefore, reagents targeting additional pockets are essential to fully understand linkage specificity. We report the development of active site-directed probes and fluorogenic substrates, based on non-hydrolyzable diubiquitin, that are equipped with a C-terminal warhead or a fluorogenic activity reporter moiety. We demonstrate that various DUBs in lysates display differential reactivity toward differently linked diubiquitin probes, as exemplified by the proteasome-associated DUB USP14. In addition, OTUD2 and OTUD3 show remarkable linkage-specific reactivity with our diubiquitin-based reagents.",2016 Apr 21,"['Flierman, Dennis', 'van\xa0der\xa0Heden\xa0van\xa0Noort, Gerbrand\xa0J.', 'Ekkebus, Reggy', 'Geurink, Paul\xa0P.', 'Mevissen, Tycho\xa0E.T.', 'Hospenthal, Manuela\xa0K.', 'Komander, David', 'Ovaa, Huib']",Cell Chem Biol,,,False
d3ca5f2f620d495c747bac2a00b3446b392f7535,PMC,Direct molecular detection of a broad range of bacterial and viral organisms and Streptococcus pneumoniae vaccine serotypes in children with otitis media with effusion,http://dx.doi.org/10.1186/s13104-016-2040-4,PMC4850712,27130295,CC BY,"BACKGROUND: Otitis media with effusion (OME) causes significant morbidity in children, but the causes of OME and methods for prevention are unclear. To look for potential infectious etiologies, we performed a pilot study using multiple-target real-time polymerase chain reaction (qPCR) for 27 infectious agents, including nine bacterial organisms and 18 respiratory viruses in middle ear fluids (MEFs) from children with OME. QPCR was also performed for the 13 Streptococcus pneumoniae serotypes contained in the current vaccine. RESULTS: Forty-eight MEF samples were obtained and qPCR detected bacterial nucleic acid (NA) in 39/48 (81 %) and viral NA in 7/48 (15 %). Alloiococcus otitidis and S. pneumoniae were both detected in 15/48 (31 %) MEFs, followed by M. catarrhalis in 14/48 (29 %), H. influenzae in 5/48 (10 %) and M. pneumoniae in 4/48 (8 %). Rhinoviruses were most common virus type detected, found in 4/48 (8 %) MEFs. Serotypes included in the current 13-serotype vaccine were detected in only 3/15 (20 %) S. pneumoniae qPCR-positive MEFs. CONCLUSIONS: Bacteria may play an important role in OME, since over 80 % of MEFs contained bacterial NA. Further research into the role of A. otitidis in OME will be helpful. Serotypes of S. pneumoniae not included in the current 13-serotype vaccine may be involved in OME. Larger studies of OME S. pneumoniae serotypes are needed to help determine which additional serotypes should be included in future vaccine formulations in order to try to prevent OME.",2016 Apr 29,"['Slinger, Robert', 'Duval, Melanie', 'Langill, Jonathan', 'Bromwich, Matthew', 'MacCormick, Johnna', 'Chan, Francis', 'Vaccani, Jean-Philippe']",BMC Res Notes,,,True
794b00331ade89870f1475a4c765b8c32ac855b5,PMC,Complete Genome Sequence of Middle East Respiratory Syndrome Coronavirus Isolated from a Dromedary Camel in Egypt,http://dx.doi.org/10.1128/genomeA.00309-16,PMC4850855,27125484,CC BY,We generated the near-full genome sequence of Middle East respiratory syndrome coronavirus (MERS-CoV) from a collected nasal sample of dromedary camel in Egypt. The newly characterized Egyptian strain has high similarity to the previously characterized Egyptian virus and both of viruses fell into a cluster distinct from other MERS-CoVs.,2016 Apr 28,"['Kandeil, Ahmed', 'Shehata, Mahmoud M.', 'El Shesheny, Rabeh', 'Gomaa, Mokhtar R.', 'Ali, Mohamed A.', 'Kayali, Ghazi']",Genome Announc,,,True
9221c3ed344b506c1208f8c2c4f9bf31f60b89da,PMC,“TRP inflammation” relationship in cardiovascular system,http://dx.doi.org/10.1007/s00281-015-0536-y,PMC4851701,26482920,CC BY,"Despite considerable advances in the research and treatment, the precise relationship between inflammation and cardiovascular (CV) disease remains incompletely understood. Therefore, understanding the immunoinflammatory processes underlying the initiation, progression, and exacerbation of many cardiovascular diseases is of prime importance. The innate immune system has an ancient origin and is well conserved across species. Its activation occurs in response to pathogens or tissue injury. Recent studies suggest that altered ionic balance, and production of noxious gaseous mediators link to immune and inflammatory responses with altered ion channel expression and function. Among plausible candidates for this are transient receptor potential (TRP) channels that function as polymodal sensors and scaffolding proteins involved in many physiological and pathological processes. In this review, we will first focus on the relevance of TRP channel to both exogenous and endogenous factors related to innate immune response and transcription factors related to sustained inflammatory status. The emerging role of inflammasome to regulate innate immunity and its possible connection to TRP channels will also be discussed. Secondly, we will discuss about the linkage of TRP channels to inflammatory CV diseases, from a viewpoint of inflammation in a general sense which is not restricted to the innate immunity. These knowledge may serve to provide new insights into the pathogenesis of various inflammatory CV diseases and their novel therapeutic strategies.",2016 Oct 19,"['Numata, Tomohiro', 'Takahashi, Kiriko', 'Inoue, Ryuji']",Semin Immunopathol,,,True
377d9d0d1f580860076b5799e30babd834eda260,PMC,"On Temporal Patterns and Circulation of Influenza Virus Strains in Taiwan, 2008-2014: Implications of 2009 pH1N1 Pandemic",http://dx.doi.org/10.1371/journal.pone.0154695,PMC4854472,27139905,CC BY,"BACKGROUND: It has been observed that, historically, strains of pandemic influenza led to succeeding seasonal waves, albeit with decidedly different patterns. Recent studies suggest that the 2009 A(H1N1)pdm09 pandemic has had an impact on the circulation patterns of seasonal influenza strains in the post-pandemic years. In this work we aim to investigate this issue and also to compare the relative transmissibility of these waves of differing strains using Taiwan influenza surveillance data before, during and after the pandemic. METHODS: We make use of the Taiwan Center for Disease Control and Prevention influenza surveillance data on laboratory-confirmed subtyping of samples and a mathematical model to determine the waves of circulating (and co-circulating) H1, H3 and B virus strains in Taiwan during 2008–2014; or namely, short before, during and after the 2009 pandemic. We further pinpoint the turning points and relative transmissibility of each wave, in order to ascertain whether any temporal pattern exists. RESULTS/FINDINGS: For two consecutive years following the 2009 pandemic, A(H1N1)pdm09 circulated in Taiwan (as in most of Northern Hemisphere), sometimes co-circulating with AH3. From the evolution point of view, A(H1N1)pdm09 and AH3 were able to sustain their circulation patterns to the end of 2010. In fact, A(H1N1)pdm09 virus circulated in six separate waves in Taiwan between summer of 2009 and spring of 2014. Since 2009, a wave of A(H1N1)pmd09 occurred every fall/winter influenza season during our study period except 2011–2012 season, when mainly influenza strain B circulated. In comparing transmissibility, while the estimated per capita weekly growth rates for cumulative case numbers (and the reproduction number) seem to be lower for most of the influenza B waves (0.06~0.26; range of 95% CIs: 0.05~0.32) when compared to those of influenza A, the wave of influenza B from week 8 to week 38 of 2010 immediately following the fall/winter wave of 2009 A(H1N1) pdm09 was substantially higher at r = 0.89 (95% CI: 0.49, 1.28), in fact highest among all the waves detected in this study. Moreover, when AH3 or A(H1N1)pdm09 exhibit high incidence, reported cases of subtype B decreases and vice versa. Further modeling analysis indicated that during the study period, Taiwan nearly experienced at least one wave of influenza epidemic of some strain every summer except in 2012. DISCUSSION: Estimates of R for seasonal influenza are consistent with that of temperate and tropical-subtropical regions, while estimate of R for A(H1N1)pdm09 is comparatively less than countries in Europe and North America, but similar to that of tropical-subtropical regions. This offers indication of regional differences in transmissibility of influenza virus that exists only for pandemic influenza. Despite obvious limitations in the data used, this study, designed to qualitatively compare the temporal patterns and transmissibility of the waves of different strains, illustrates how influenza subtyping data can be utilized to explore the mechanism for various influenza strains to compete or to circulate, to possibly provide predictors of future trends in the evolution of influenza viruses of various subtypes, and perhaps more importantly, to be of use to future annual seasonal influenza vaccine design.",2016 May 3,"['Hsieh, Ying-Hen', 'Huang, Hsiang-Min', 'Lan, Yu-Ching']",PLoS One,,,True
b2f39f20e4e523aab2915f1d22d29d6a29110a20,PMC,Identification of a Peptide Produced by Bifidobacterium longum CECT 7210 with Antirotaviral Activity,http://dx.doi.org/10.3389/fmicb.2016.00655,PMC4855034,27199974,CC BY,"Rotavirus is one of the main causes of acute diarrhea and enteritis in infants. Currently, studies are underway to assess the use of probiotics to improve rotavirus vaccine protection. A previous work demonstrated that the probiotic strain Bifidobacterium longum subsp. infantis CECT 7210 is able to hinder rotavirus replication both in vitro and in vivo. The present study takes a systematic approach in order to identify the molecule directly involved in rotavirus inhibition. Supernatant protease digestions revealed both the proteinaceous nature of the active substance and the fact that the molecule responsible for inhibiting rotavirus replication is released to the supernatant. Following purification by cationic exchange chromatography, active fractions were obtained and the functional compound was identified as an 11-amino acid peptide (MHQPHQPLPPT, named 11-mer peptide) with a molecular mass of 1.282 KDa. The functionality of 11-mer was verified using the synthesized peptide in Wa, Ito, and VA70 rotavirus infections of both HT-29 and MA-104 cell lines. Finally, protease activity was detected in B. longum subsp. infantis CECT 7210 supernatant, which releases 11-mer peptide. A preliminary identification of the protease is also included in the study.",2016 May 4,"['Chenoll, Empar', 'Casinos, Beatriz', 'Bataller, Esther', 'Buesa, Javier', 'Ramón, Daniel', 'Genovés, Salvador', 'Fábrega, Joan', 'Rivero Urgell, Montserrat', 'Moreno Muñoz, José A.']",Front Microbiol,,,True
c4a6612ba3d6a23317a85c42cedd5e6d2f317a9c,PMC,DNA immunization as a technology platform for monoclonal antibody induction,http://dx.doi.org/10.1038/emi.2016.27,PMC4855071,27048742,CC BY,"To combat the threat of many emerging infectious diseases, DNA immunization offers a unique and powerful approach to the production of high-quality monoclonal antibodies (mAbs) against various pathogens. Compared with traditional protein-based immunization approaches, DNA immunization is efficient for testing novel immunogen designs, does not require the production or purification of proteins from a pathogen or the use of recombinant protein technology and is effective at generating mAbs against conformation-sensitive targets. Although significant progress in the use of DNA immunization to generate mAbs has been made over the last two decades, the literature does not contain an updated summary of this experience. The current review provides a comprehensive analysis of the literature, including our own work, describing the use of DNA immunization to produce highly functional mAbs, in particular, those against emerging infectious diseases. Critical factors such as immunogen design, delivery approach, immunization schedule, use of immune modulators and the role of final boost immunization are discussed in detail.",2016 Apr 6,"['Liu, Shuying', 'Wang, Shixia', 'Lu, Shan']",Emerg Microbes Infect,,,True
aa973f2833829b97ebdfd6ce2ac6a29b9100db3a,PMC,Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3,http://dx.doi.org/10.1038/emi.2016.33,PMC4855074,27094905,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) infection has claimed hundreds of lives and has become a global threat since its emergence in Saudi Arabia in 2012. The ability of MERS-CoV to evade the host innate antiviral response may contribute to its severe pathogenesis. Many MERS-CoV-encoded proteins were identified to have interferon (IFN)-antagonizing properties, which correlates well with the reduced IFN levels observed in infected patients and ex vivo models. In this study, we fully characterized the IFN-antagonizing property of the MERS-CoV M protein. Expression of MERS-CoV M protein suppressed type I IFN expression in response to Sendai virus infection or poly(I:C) induction. This suppressive effect was found to be specific for the activation of IFN regulatory factor 3 (IRF3) but not nuclear factor-κB. MERS-CoV M protein interacted with TRAF3 and disrupted TRAF3–TBK1 association leading to reduced IRF3 activation. M proteins from MERS-CoV and SARS-CoV have three highly similar conserved N-terminal transmembrane domains and a C-terminal region. Using chimeric and truncation mutants, the N-terminal transmembrane domains of the MERS-CoV M protein were found to be sufficient for its inhibitory effect on IFN expression, whereas the C-terminal domain was unable to induce this suppression. Collectively, our findings suggest a common and conserved mechanism through which highly pathogenic MERS-CoV and SARS-CoV harness their M proteins to suppress type I IFN expression at the level of TBK1-dependent phosphorylation and activation of IRF3 resulting in evasion of the host innate antiviral response.",2016 Apr 20,"['Lui, Pak-Yin', 'Wong, Lok-Yin Roy', 'Fung, Cheuk-Lai', 'Siu, Kam-Leung', 'Yeung, Man-Lung', 'Yuen, Kit-San', 'Chan, Chi-Ping', 'Woo, Patrick Chiu-Yat', 'Yuen, Kwok-Yung', 'Jin, Dong-Yan']",Emerg Microbes Infect,,,True
d52f0060c0eefc59aa2383d4951125726984fab3,PMC,Intranasal application of polyethyleneimine suppresses influenza virus infection in mice,http://dx.doi.org/10.1038/emi.2016.64,PMC4855075,27118070,CC BY,,2016 Apr 27,"['He, Biao', 'Fu, Yuhong', 'Xia, Shuai', 'Yu, Fei', 'Wang, Qian', 'Lu, Lu', 'Jiang, Shibo']",Emerg Microbes Infect,,,True
9dff93ed512a5e207595d61ad2122f39971e5662,PMC,Intranasal application of polyethyleneimine suppresses influenza virus infection in mice,http://dx.doi.org/10.1038/emi.2016.64,PMC4855075,27118070,CC BY,,2016 Apr 27,"['He, Biao', 'Fu, Yuhong', 'Xia, Shuai', 'Yu, Fei', 'Wang, Qian', 'Lu, Lu', 'Jiang, Shibo']",Emerg Microbes Infect,,,False
576bad43bf08b1a2d302695f5624a77fdbcaf6d0,PMC,"Evolutionary Dynamics of MERS-CoV: Potential Recombination, Positive Selection and Transmission",http://dx.doi.org/10.1038/srep25049,PMC4855236,27142087,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to beta group of coronavirus and was first discovered in 2012. MERS-CoV can infect multiple host species and cause severe diseases in human. We conducted a series of phylogenetic and bioinformatic analyses to study the evolution dynamics of MERS-CoV among different host species with genomic data. Our analyses show: 1) 28 potential recombinant sequences were detected and they can be classified into seven potential recombinant types; 2) The spike (S) protein of MERS-CoV was under strong positive selection when MERS-CoV transmitted from their natural host to human; 3) Six out of nine positive selection sites detected in spike (S) protein are located in its receptor-binding domain which is in direct contact with host cells; 4) MERS-CoV frequently transmitted back and forth between human and camel after it had acquired the human-camel infection capability. Together, these results suggest that potential recombination events might have happened frequently during MERS-CoV’s evolutionary history and the positive selection sites in MERS-CoV’s S protein might enable it to infect human.",2016 May 4,"['Zhang, Zhao', 'Shen, Libing', 'Gu, Xun']",Sci Rep,,,True
d82d6db1f132aa8d31e7b5afff09c1679e2dfe4e,PMC,Display of recombinant proteins at the surface of lactic acid bacteria: strategies and applications,http://dx.doi.org/10.1186/s12934-016-0468-9,PMC4855500,27142045,CC BY,"Lactic acid bacteria (LAB) are promising vectors of choice to deliver active molecules to mucosal tissues. They are recognized as safe by the World Health Organization and some strains have probiotic properties. The wide range of potential applications of LAB-driven mucosal delivery includes control of inflammatory bowel disease, vaccine delivery, and management of auto-immune diseases. Because of this potential, strategies for the display of proteins at the surface of LAB are gaining interest. To display a protein at the surface of LAB, a signal peptide and an anchor domain are necessary. The recombinant protein can be attached to the membrane layer, using a transmembrane anchor or a lipoprotein-anchor, or to the cell wall, by a covalent link using sortase mediated anchoring via the LPXTG motif, or by non-covalent liaisons employing binding domains such as LysM or WxL. Both the stability and functionality of the displayed proteins will be affected by the kind of anchor used. The most commonly surfaced exposed recombinant proteins produced in LAB are antigens and antibodies and the most commonly used LAB are lactococci and lactobacilli. Although it is not necessarily so that surface-display is the preferred localization in all cases, it has been shown that for certain applications, such as delivery of the human papillomavirus E7 antigen, surface-display elicits better biological responses, compared to cytosolic expression or secretion. Recent developments include the display of peptides and proteins targeting host cell receptors, for the purpose of enhancing the interactions between LAB and host. Surface-display technologies have other potential applications, such as degradation of biomass, which is of importance for some potential industrial applications of LAB.",2016 May 3,"['Michon, C.', 'Langella, P.', 'Eijsink, V. G. H.', 'Mathiesen, G.', 'Chatel, J. M.']",Microb Cell Fact,,,True
1f534cb2b4a2d3482affcb6d7a1dd23be34f9321,PMC,PER1 prevents excessive innate immune response during endotoxin-induced liver injury through regulation of macrophage recruitment in mice,http://dx.doi.org/10.1038/cddis.2016.9,PMC4855679,27054331,CC BY,"The severity of acute liver failure (ALF) induced by bacterial lipopolysaccharide (LPS) is associated with the hepatic innate immune response. The core circadian molecular clock modulates the innate immune response by controlling rhythmic pathogen recognition by the innate immune system and daily variations in cytokine gene expression. However, the molecular link between circadian genes and the innate immune system has remained unclear. Here, we showed that mice lacking the clock gene Per1 (Period1) are more susceptible to LPS/d-galactosamine (LPS/GalN)-induced macrophage-dependent ALF compared with wild-type (WT) mice. Per1 deletion caused a remarkable increase in the number of Kupffer cells (KCs) in the liver, resulting in an elevation of the levels of pro-inflammatory cytokines after LPS treatment. Loss of Per1 had no effect on the proliferation or apoptosis of macrophages; however, it enhanced the recruitment of macrophages, which was associated with an increase in CC chemokine receptor 2 (Ccr2) expression levels in monocytes/macrophages. Deletion of Ccr2 rescued d-GalN/LPS-induced liver injury in Per1(−/−) mice. We demonstrated that the upregulation of Ccr2 expression by Per1 deletion could be reversed by the synthetic peroxisome proliferator-activated receptor gamma (PPAR-γ) antagonist GW9662. Further analysis indicated that PER1 binds to PPAR-γ on the Ccr2 promoter and enhanced the inhibitory effect of PPAR-γ on Ccr2 expression. These results reveal that Per1 reduces hepatic macrophage recruitment through interaction with PPAR-γ and prevents an excessive innate immune response in endotoxin-induced liver injury.",2016 Apr 7,"['Wang, T', 'Wang, Z', 'Yang, P', 'Xia, L', 'Zhou, M', 'Wang, S', 'Du, Jie', 'Zhang, J']",Cell Death Dis,,,True
7fdea1d57d5d3d0ee393379c8437b0393f0ce542,PMC,"Epithelial cell lines of the cotton rat (Sigmodon hispidus) are highly susceptible in vitro models to zoonotic Bunya-, Rhabdo-, and Flaviviruses",http://dx.doi.org/10.1186/s12985-016-0531-5,PMC4855710,27142375,CC BY,"BACKGROUND: Small mammals such as bats and rodents have been increasingly recognized as reservoirs of novel potentially zoonotic pathogens. However, few in vitro model systems to date allow assessment of zoonotic viruses in a relevant host context. The cotton rat (Sigmodon hispidus) is a New World rodent species that has a long-standing history as an experimental animal model due to its unique susceptibility to human viruses. Furthermore, wild cotton rats are associated with a large variety of known or potentially zoonotic pathogens. METHODS: A method for the isolation and culture of airway epithelial cell lines recently developed for bats was applied for the generation of rodent airway and renal epithelial cell lines from the cotton rat. Continuous cell lines were characterized for their epithelial properties as well as for their interferon competence. Susceptibility to members of zoonotic Bunya-, Rhabdo-, and Flaviviridae, in particular Rift Valley fever virus (RVFV), vesicular stomatitis virus (VSV), West Nile virus (WNV), and tick-borne encephalitis virus (TBEV) was tested. Furthermore, novel arthropod-derived viruses belonging to the families Bunya-, Rhabdo-, and Mesoniviridae were tested. RESULTS: We successfully established airway and kidney epithelial cell lines from the cotton rat, and characterized their epithelial properties. Cells were shown to be interferon-competent. Viral infection assays showed high-titre viral replication of RVFV, VSV, WNV, and TBEV, as well as production of infectious virus particles. No viral replication was observed for novel arthropod-derived members of the Bunya-, Rhabdo-, and Mesoniviridae families in these cell lines. CONCLUSION: In the current study, we showed that newly established cell lines from the cotton rat can serve as host-specific in vitro models for viral infection experiments. These cell lines may also serve as novel tools for virus isolation, as well as for the investigation of virus-host interactions in a relevant host species.",2016 May 4,"['Ehlen, Lukas', 'Tödtmann, Jan', 'Specht, Sabine', 'Kallies, René', 'Papies, Jan', 'Müller, Marcel A.', 'Junglen, Sandra', 'Drosten, Christian', 'Eckerle, Isabella']",Virol J,,,True
10f87d75360ca119636fcd75da502bcb0bf7845d,PMC,Qualitative study on the shifting sociocultural meanings of the facemask in Hong Kong since the severe acute respiratory syndrome (SARS) outbreak: implications for infection control in the post-SARS era,http://dx.doi.org/10.1186/s12939-016-0358-0,PMC4855818,27145823,CC BY,"BACKGROUND: The clinical importance and efficacy of facemasks in infection prevention have been documented in the international literature. Past studies have shown that the perceived susceptibility, the perceived severity of being afflicted with life-threatening diseases, and the perceived benefits of using a facemask are predictors of a person’s use of a facemask. However, I argue that people wear a facemask not merely for infection prevention, and various sociocultural reasons have been motivating people to wear (and not wear) a facemask. Facemasks thus have sociocultural implications for people. Research on the sociocultural meanings of facemasks is scant, and even less is known on how the shifting sociocultural meanings of facemasks are related to the changing social environment, which, I argue, serve as remarkable underlying factors for people using (and not using) facemasks. As new infectious diseases such as avian influenza and Middle East Respiratory Syndrome have been emerging, threatening people’s health worldwide, and because facemasks have been documented to have substantial efficacy in the prevention of infection transmission, understanding the sociocultural meanings of facemasks has significant implications for public health policymakers and health care providers in designing a socially and culturally responsive public health and infection control policy for the community. METHODS: A qualitative research design involving the use of 40 individual, in-depth semistructured interviews and a phenomenological analysis approach were adopted. RESULTS: The sociocultural meanings of the facemask have been undergoing constant change, from positive to negative, which resulted in the participants displaying hesitation in using a facemask in the post-SARS era. Because it represents a violation of societal ideologies and traditional Chinese cultural beliefs, the meanings of the facemask that had developed during the SARS outbreak failed to be sustained in the post-SARS era. CONCLUSION: The changes in meaning not only influenced the participants’ perceptions of the facemask but also influenced their perceptions of people who use facemasks, which ultimately influenced their health behavior, preventing them from using facemasks in the post-SARS era. These findings have critical implications for designing a culturally responsive infection prevention and facemask usage policy in the future.",2016 May 4,"Siu, Judy Yuen-man",Int J Equity Health,,,True
1e2493a8e26be4ff934b96dedc32dc7cf5728370,PMC,Trigger factor assisted soluble expression of recombinant spike protein of porcine epidemic diarrhea virus in Escherichia coli,http://dx.doi.org/10.1186/s12896-016-0268-7,PMC4855837,27142206,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric pathogen of swine. The spike glycoprotein (S) of PEDV is the major immunogenic determinant that plays a pivotal role in the induction of neutralizing antibodies against PEDV, which therefore is an ideal target for the development of subunit vaccine. In an attempt to develop a subunit vaccine for PEDV, we cloned two different fragments of S protein and expressed as glutathione S-transferase (GST)-tagged fusion proteins, namely rGST-COE and rGST-S1D, in E.coli. However, the expression of these recombinant protein antigens using a variety of expression vectors, strains, and induction conditions invariably resulted in inclusion bodies. To achieve the soluble expression of recombinant proteins, several chaperone co-expression systems were tested in this study. RESULTS: We firstly tested various chaperone co-expression systems and found that co-expression of trigger factor (TF) with recombinant proteins at 15 °C was most useful in soluble production of rGST-COE and rGST-S1D compared to GroEL-ES and DnaK-DnaJ-GrpE/GroEL-ES systems. The soluble rGST-COE and rGST-S1D were purified using glutathione Sepharose 4B with a yield of 7.5 mg/l and 5 mg/l, respectively. Purified proteins were detected by western blot using mouse anti-GST mAb and pig anti-PEDV immune sera. In an indirect ELISA, purified proteins showed immune reactivity with pig anti-PEDV immune sera. Finally, immunization of mice with 10 μg of purified proteins elicited highly potent serum IgG and serum neutralizing antibody titers. CONCLUSIONS: In this study, soluble production of recombinant spike protein of PEDV, rGST-COE and rGST-S1D, were achieved by using TF chaperone co-expression system. Our results suggest that soluble rGST-COE and rGST-S1D produced by co-expressing chaperones may have the potential to be used as subunit vaccine antigens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12896-016-0268-7) contains supplementary material, which is available to authorized users.",2016 May 4,"['Piao, Da-Chuan', 'Shin, Do-Woon', 'Kim, In-Seon', 'Li, Hui-Shan', 'Oh, Seo-Ho', 'Singh, Bijay', 'Maharjan, S.', 'Lee, Yoon-Seok', 'Bok, Jin-Duck', 'Cho, Chong-Su', 'Hong, Zhong-Shan', 'Kang, Sang-Kee', 'Choi, Yun-Jaie']",BMC Biotechnol,,,True
ceab18d97f09ef0d9030f0c808f7ab5ab1c7d583,PMC,NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap(4)A) and Down-Regulates Immune Response and Cancer Promotion Genes,http://dx.doi.org/10.1371/journal.pone.0154674,PMC4856261,27144453,CC BY,"Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap(4)A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap(4)A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap(4)A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity(®) Pathway Analysis (IPA(®)) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA(®) for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap(4)A and/or NUDT2 disruption include binding of Ap(4)A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap(4)A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap(4)A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis.",2016 May 4,"['Marriott, Andrew S.', 'Vasieva, Olga', 'Fang, Yongxiang', 'Copeland, Nikki A.', 'McLennan, Alexander G.', 'Jones, Nigel J.']",PLoS One,,,True
58086bd6aa7a845eac58001de931144a3cebd644,PMC,Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity,http://dx.doi.org/10.1038/srep25359,PMC4857172,27146253,CC BY,"Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.",2016 May 5,"['Min, Chan-Ki', 'Cheon, Shinhye', 'Ha, Na-Young', 'Sohn, Kyung Mok', 'Kim, Yuri', 'Aigerim, Abdimadiyeva', 'Shin, Hyun Mu', 'Choi, Ji-Yeob', 'Inn, Kyung-Soo', 'Kim, Jin-Hwan', 'Moon, Jae Young', 'Choi, Myung-Sik', 'Cho, Nam-Hyuk', 'Kim, Yeon-Sook']",Sci Rep,,,True
ce374c50076cc3e74a12e5b910cae08d2fe543ba,PMC,Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity,http://dx.doi.org/10.1038/srep25359,PMC4857172,27146253,CC BY,"Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.",2016 May 5,"['Min, Chan-Ki', 'Cheon, Shinhye', 'Ha, Na-Young', 'Sohn, Kyung Mok', 'Kim, Yuri', 'Aigerim, Abdimadiyeva', 'Shin, Hyun Mu', 'Choi, Ji-Yeob', 'Inn, Kyung-Soo', 'Kim, Jin-Hwan', 'Moon, Jae Young', 'Choi, Myung-Sik', 'Cho, Nam-Hyuk', 'Kim, Yeon-Sook']",Sci Rep,,,False
5d9e52011787ca962e5391dd027c6641a37f9cba,PMC,"Survival functions for defining a clinical management Lost To Follow-Up (LTFU) cut-off in Antiretroviral Therapy (ART) program in Zomba, Malawi",http://dx.doi.org/10.1186/s12911-016-0290-7,PMC4857410,27150958,CC BY,"BACKGROUND: While, lost to follow-up (LTFU) from antiretroviral therapy (ART) can be considered a catch-all category for patients who miss scheduled visits or medication pick-ups, operational definitions and methods for defining LTFU vary making comparisons across programs challenging. Using weekly cut-offs, we sought to determine the probability that an individual would return to clinic given that they had not yet returned in order to identify the LTFU cut-off that could be used to inform clinical management and tracing procedures. METHODS: Individuals who initiated ART with Dignitas International supported sites (n = 22) in Zomba, Malawi between January 1 2007-June 30 2010 and were ≥ 1 week late for a follow-up visit were included. Lateness was categorized using weekly cut-offs from ≥1 to ≥26 weeks late. At each weekly cut-off, the proportion of patients who returned for a subsequent follow-up visit were identified. Cumulative Distribution Functions (CDFs) were plotted to determine the probability of returning as a function of lateness. Hazard functions were plotted to demonstrate the proportion of patients who returned each weekly interval relative to those who had yet to return. RESULTS: In total, n = 4484 patients with n = 7316 follow-up visits were included. The number of included follow-up visits per patient ranged from 1–10 (median: 1). Both the CDF and hazard function demonstrated that after being ≥9 weeks late, the proportion of new patients who returned relative to those who had yet to return decreased substantially. CONCLUSIONS: We identified a LTFU definition useful for clinical management. The simple functions plotted here did not require advanced statistical expertise and were created using Microsoft Excel, making it a particularly practical method for HIV programs in resource-constrained settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12911-016-0290-7) contains supplementary material, which is available to authorized users.",2016 May 5,"['Rachlis, Beth', 'Cole, Donald C.', 'van Lettow, Monique', 'Escobar, Michael']",BMC Med Inform Decis Mak,,,True
5edd56f96660760a5f8ae69efd7d9e976a00c4ee,PMC,Immunogenicity of Virus Like Particle Forming Baculoviral DNA Vaccine against Pandemic Influenza H1N1,http://dx.doi.org/10.1371/journal.pone.0154824,PMC4858234,27149064,CC BY,"An outbreak of influenza H1N1 in 2009, representing the first influenza pandemic of the 21st century, was transmitted to over a million individuals and claimed 18,449 lives. The current status in many countries is to prepare influenza vaccine using cell-based or egg-based killed vaccine. However, traditional influenza vaccine platforms have several limitations. To overcome these limitations, many researchers have tried various approaches to develop alternative production platforms. One of the alternative approach, we reported the efficacy of influenza HA vaccination using a baculoviral DNA vaccine (AcHERV-HA). However, the immune response elicited by the AcHERV-HA vaccine, which only targets the HA antigen, was lower than that of the commercial killed vaccine. To overcome the limitations of this previous vaccine, we constructed a human endogenous retrovirus (HERV) envelope-coated, baculovirus-based, virus-like-particle (VLP)–forming DNA vaccine (termed AcHERV-VLP) against pandemic influenza A/California/04/2009 (pH1N1). BALB/c mice immunized with AcHERV-VLP (1×10(7) FFU AcHERV-VLP, i.m.) and compared with mice immunized with the killed vaccine or mice immunized with AcHERV-HA. As a result, AcHERV-VLP immunization produced a greater humoral immune response and exhibited neutralizing activity with an intrasubgroup H1 strain (PR8), elicited neutralizing antibody production, a high level of interferon-γ secretion in splenocytes, and diminished virus shedding in the lung after challenge with a lethal dose of influenza virus. In conclusion, VLP-forming baculovirus DNA vaccine could be a potential vaccine candidate capable of efficiently delivering DNA to the vaccinee and VLP forming DNA eliciting stronger immunogenicity than egg-based killed vaccines.",2016 May 5,"['Gwon, Yong-Dae', 'Kim, Sehyun', 'Cho, Yeondong', 'Heo, Yoonki', 'Cho, Hansam', 'Park, Kihoon', 'Lee, Hee-Jung', 'Choi, Jiwon', 'Poo, Haryoung', 'Kim, Young Bong']",PLoS One,,,True
106b81593063e1df0817b8ca2e0a90823003201d,PMC,Immunogenicity of Virus Like Particle Forming Baculoviral DNA Vaccine against Pandemic Influenza H1N1,http://dx.doi.org/10.1371/journal.pone.0154824,PMC4858234,27149064,CC BY,"An outbreak of influenza H1N1 in 2009, representing the first influenza pandemic of the 21st century, was transmitted to over a million individuals and claimed 18,449 lives. The current status in many countries is to prepare influenza vaccine using cell-based or egg-based killed vaccine. However, traditional influenza vaccine platforms have several limitations. To overcome these limitations, many researchers have tried various approaches to develop alternative production platforms. One of the alternative approach, we reported the efficacy of influenza HA vaccination using a baculoviral DNA vaccine (AcHERV-HA). However, the immune response elicited by the AcHERV-HA vaccine, which only targets the HA antigen, was lower than that of the commercial killed vaccine. To overcome the limitations of this previous vaccine, we constructed a human endogenous retrovirus (HERV) envelope-coated, baculovirus-based, virus-like-particle (VLP)–forming DNA vaccine (termed AcHERV-VLP) against pandemic influenza A/California/04/2009 (pH1N1). BALB/c mice immunized with AcHERV-VLP (1×10(7) FFU AcHERV-VLP, i.m.) and compared with mice immunized with the killed vaccine or mice immunized with AcHERV-HA. As a result, AcHERV-VLP immunization produced a greater humoral immune response and exhibited neutralizing activity with an intrasubgroup H1 strain (PR8), elicited neutralizing antibody production, a high level of interferon-γ secretion in splenocytes, and diminished virus shedding in the lung after challenge with a lethal dose of influenza virus. In conclusion, VLP-forming baculovirus DNA vaccine could be a potential vaccine candidate capable of efficiently delivering DNA to the vaccinee and VLP forming DNA eliciting stronger immunogenicity than egg-based killed vaccines.",2016 May 5,"['Gwon, Yong-Dae', 'Kim, Sehyun', 'Cho, Yeondong', 'Heo, Yoonki', 'Cho, Hansam', 'Park, Kihoon', 'Lee, Hee-Jung', 'Choi, Jiwon', 'Poo, Haryoung', 'Kim, Young Bong']",PLoS One,,,True
275dd71da13e09fcace07d5824ac14a2c38d1df1,PMC,The 2014–2015 Ebola outbreak in West Africa: Hands On,http://dx.doi.org/10.1186/s13756-016-0112-9,PMC4858848,,CC BY,"The International Consortium for Prevention and Infection Control (ICPIC) organises a biannual conference (ICPIC) on various subjects related to infection prevention, treatment and control. During ICPIC 2015, held in Geneva in June 2015, a full one-day session focused on the 2014–2015 Ebola virus disease (EVD) outbreak in West Africa. This article is a non-exhaustive compilation of these discussions. It concentrates on lessons learned and imagining a way forward for the communities most affected by the epidemic. The reader can access video recordings of all lectures delivered during this one-day session, as referenced. Topics include the timeline of the international response, linkages between the dynamics of the epidemic and infection prevention and control, the importance of community engagement, and updates on virology, diagnosis, treatment and vaccination issues. The paper also includes discussions from public health, infectious diseases, critical care and infection control experts who cared for patients with EVD in Africa, in Europe, and in the United Sates and were involved in Ebola preparedness in both high- and low-resource settings and countries. This review concludes that too little is known about the pathogenesis and treatment of EVD, therefore basic and applied research in this area are urgently required. Furthermore, it is clear that epidemic preparedness needs to improve globally, in particular through the strengthening of health systems at local and national levels. There is a strong need for culturally sensitive approaches to public health which could be designed and delivered by social scientists and medical professionals working together. As of December 2015, this epidemic killed more than 11,000 people and infected more than 28,000; it has also generated more than 17,000 survivors and orphans, many of whom face somatic and psychological complications. The continued treatment and rehabilitation of these people is a public health priority, which also requires an integration of specific medical and social science approaches, not always available in West Africa.",2016 May 5,"['Vetter, Pauline', 'Dayer, Julie-Anne', 'Schibler, Manuel', 'Allegranzi, Benedetta', 'Brown, Donal', 'Calmy, Alexandra', 'Christie, Derek', 'Eremin, Sergey', 'Hagon, Olivier', 'Henderson, David', 'Iten, Anne', 'Kelley, Edward', 'Marais, Frederick', 'Ndoye, Babacar', 'Pugin, Jérôme', 'Robert-Nicoud, Hugues', 'Sterk, Esther', 'Tapper, Michael', 'Siegrist, Claire-Anne', 'Kaiser, Laurent', 'Pittet, Didier']",Antimicrob Resist Infect Control,,,True
eaba1af19b87795dc237a55c0236d89ede3cf46a,PMC,"Isolation and identification of group A rotaviruses among neonatal diarrheic calves, Morocco",http://dx.doi.org/10.1186/s13104-016-2065-8,PMC4858901,27150259,CC BY,"BACKGROUND: Group A rotaviruses (RVA) are the main cause of neonatal calve diarrhea (NCD) in Morocco. In this study, we isolated RVA strains from NCD clinical samples in order to support RVA disease control in Morocco. This isolation process constitutes a first step toward vaccine development. METHODS: Thirteen fecal samples were obtained from calves with a single episode of neonate calf diarrhea at three different dairies and two samples were collected from field during a severe NCD outbreak. Diagnosis of RVA infection was based on fecal immune-chromatographic rapid test and further evaluated for their hemagglutination (HA) activity. RVA isolation was carried out on MA104 cells after inoculates were treated with different concentrations of trypsin TPCK. All RVA isolates were confirmed by LSI VetMAX™ Triplex Ruminant Rotavirus & Coronavirus Real-Time PCR kit. G and P typing were determined by direct sequencing of the VP4 and VP7 amplicons. RESULTS: RVA isolation was achieved for nine clinical samples following one or two passages (60 %) and was properly depended on HA activity and trypsin treatment of inoculates. The first sign of CPE detected consisted of increased cell granularity, obscure cell boundaries, cell rounding, and eventual degeneration and detachment of cells. At lower TPCK concentration (3–10 μg/inoculum), no changes at the cellular level were observed, while cells activated with 25–30 μg of trypsin/inoculums, they degenerated and trypsin cytotoxicity was enhanced. Appreciable changes in cell’s morphology were detected with optimal trypsin concentration of 15–20 μg trypsin/inoculums. Data from qRT-PCR confirmed that unsuccessful cultivations have No-Ct, and all nine isolates have Ct values ranged between 12.17 and 24.69. Analysis sequencing revealed that field isolates were of G6 P[5] serotype and isolates from the dairy NCD samples were of G10 P[14] serotype. CONCLUSIONS: To our knowledge, this is the first study in Morocco which reports the circulation of G10P[14] in NCD on dairy farms and G6P[5] in the field. Our study constitutes a crucial and a necessary step allowing preventive and veterinary medicine to support RVA disease controls in the country.",2016 May 5,"['Ennima, Imane', 'Sebbar, Ghizlane', 'Harif, Bachir', 'Amzazi, Saaid', 'Loutfi, Chafiqa', 'Touil, Nadia']",BMC Res Notes,,,True
53d4dd6acd3501c47b364dbae1ba3dd2083b895a,PMC,Presentation and outcome of Middle East respiratory syndrome in Saudi intensive care unit patients,http://dx.doi.org/10.1186/s13054-016-1303-8,PMC4859954,27153800,CC BY,"BACKGROUND: Middle East respiratory syndrome coronavirus infection is associated with high mortality rates but limited clinical data have been reported. We describe the clinical features and outcomes of patients admitted to an intensive care unit (ICU) with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. METHODS: Retrospective analysis of data from all adult (>18 years old) patients admitted to our 20-bed mixed ICU with Middle East respiratory syndrome coronavirus infection between October 1, 2012 and May 31, 2014. Diagnosis was confirmed in all patients using real-time reverse transcription polymerase chain reaction on respiratory samples. RESULTS: During the observation period, 31 patients were admitted with MERS-CoV infection (mean age 59 ± 20 years, 22 [71 %] males). Cough and tachypnea were reported in all patients; 22 (77.4 %) patients had bilateral pulmonary infiltrates. Invasive mechanical ventilation was applied in 27 (87.1 %) and vasopressor therapy in 25 (80.6 %) patients during the intensive care unit stay. Twenty-three (74.2 %) patients died in the ICU. Nonsurvivors were older, had greater APACHE II and SOFA scores on admission, and were more likely to have received invasive mechanical ventilation and vasopressor therapy. After adjustment for the severity of illness and the degree of organ dysfunction, the need for vasopressors was an independent risk factor for death in the ICU (odds ratio = 18.33, 95 % confidence interval: 1.11–302.1, P = 0.04). CONCLUSIONS: MERS-CoV infection requiring admission to the ICU is associated with high morbidity and mortality. The need for vasopressor therapy is the main risk factor for death in these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1303-8) contains supplementary material, which is available to authorized users.",2016 May 7,"['Almekhlafi, Ghaleb A.', 'Albarrak, Mohammed M.', 'Mandourah, Yasser', 'Hassan, Sahar', 'Alwan, Abid', 'Abudayah, Abdullah', 'Altayyar, Sultan', 'Mustafa, Mohamed', 'Aldaghestani, Tareef', 'Alghamedi, Adnan', 'Talag, Ali', 'Malik, Muhammad K.', 'Omrani, Ali S.', 'Sakr, Yasser']",Crit Care,,,True
3d09812aba24146255e664c9ed4ed7d5dcd9e3b3,PMC,Dengue research: a bibliometric analysis of worldwide and Arab publications during 1872–2015,http://dx.doi.org/10.1186/s12985-016-0534-2,PMC4859974,27154247,CC BY,"BACKGROUND: Dengue is an important emerging and re-emerging arboviral infection globally as a rapidly growing and widespread public health problem, with transmission occurring in more than 128 countries in Asia, Americas, southeast Africa, western Pacific, and eastern Mediterranean regions. Therefore, the aim of this study was to characterize and quantify the scientific output of dengue research in Arab countries relative to that worldwide by using a bibliometric analysis. METHODS: The standardized search approach based on the use of the the keyword “dengue” in the title, abstract, and keyword field was used to get research output related to dengue at a global level. All data related to dengue were collected from the past to December 31, 2015. RESULTS: A total of 19,581 dengue-related documents identified in the Scopus database. The results show that the study of dengue exhibits an overall upward trend from 1872 to 2015 with peak publications in 2014. The leading countries in dengue research were the USA (4,709; 24.05 %), India (1,942; 9.92 %), Brazil (1,530; 7.81 %), Thailand (1,260; 6.43 %), the UK (1,129; 5.77 %), and France (1,087; 5.55 %). Only 226 (1.16 % of the overall global research effort in the dengue field) articles were published from the Arab region. The total number of citations for all publications was 352,710, with an average of 18.0 citations per publication. Furthermore, the h-index for all extracted data related to dengue research was 186. Kingdom of Saudi Arabia (KSA) was the most productive country in Arab region with 102 documents representing 45.1 %. Furthermore, the h-index for all extracted data related to dengue research was 27. The USA was Arab’s most main cooperative partner (46, 20.4 %), followed by India (36, 15.9 %). CONCLUSIONS: The amount of literature related to dengue research has considerably increased over the last decade. This bibliometric analysis has demonstrated the leading role that the USA, India, Brazil, Thailand, the UK, and France play in dengue research. The Arab world produced fewer publications related to dengue with lower quality than other world countries.",2016 May 6,"Zyoud, Sa’ed H.",Virol J,,,True
83c33f01d7a8c1abca6dedf7e12e485fc7ed6ed3,PMC,Cortex phellodendri Extract Relaxes Airway Smooth Muscle,http://dx.doi.org/10.1155/2016/8703239,PMC4863113,27239213,CC BY,"Cortex phellodendri is used to reduce fever and remove dampness and toxin. Berberine is an active ingredient of C. phellodendri. Berberine from Argemone ochroleuca can relax airway smooth muscle (ASM); however, whether the nonberberine component of C. phellodendri has similar relaxant action was unclear. An n-butyl alcohol extract of C. phellodendri (NBAECP, nonberberine component) was prepared, which completely inhibits high K(+)- and acetylcholine- (ACH-) induced precontraction of airway smooth muscle in tracheal rings and lung slices from control and asthmatic mice, respectively. The contraction induced by high K(+) was also blocked by nifedipine, a selective blocker of L-type Ca(2+) channels. The ACH-induced contraction was partially inhibited by nifedipine and pyrazole 3, an inhibitor of TRPC3 and STIM/Orai channels. Taken together, our data demonstrate that NBAECP can relax ASM by inhibiting L-type Ca(2+) channels and TRPC3 and/or STIM/Orai channels, suggesting that NBAECP could be developed to a new drug for relieving bronchospasm.",2016 Apr 27,"['Jiang, Qiu-Ju', 'Chen, Weiwei', 'Dan, Hong', 'Tan, Li', 'Zhu, He', 'Yang, Guangzhong', 'Shen, Jinhua', 'Peng, Yong-Bo', 'Zhao, Ping', 'Xue, Lu', 'Yu, Meng-Fei', 'Ma, Liqun', 'Si, Xiao-Tang', 'Wang, Zhuo', 'Dai, Jiapei', 'Qin, Gangjian', 'Zou, Chunbin', 'Liu, Qing-Hua']",Evid Based Complement Alternat Med,,,True
fb775c4af00b99294d4e8812a3f23ba6aca32774,PMC,Discovery of a Novel Bat Gammaherpesvirus,http://dx.doi.org/10.1128/mSphere.00016-16,PMC4863598,27303690,CC BY,"Zoonosis is the leading cause of emerging infectious diseases. In a recent article, R. S. Shabman et al. (mSphere 1[1]:e00070-15, 2016, http://dx.doi.org/10.1128/mSphere.00070-15) report the identification of a novel gammaherpesvirus in a cell line derived from the microbat Myotis velifer incautus. This is the first report on a replicating, infectious gammaherpesvirus from bats. The new virus is named bat gammaherpesvirus 8 (BGHV8), also known as Myotis gammaherpesvirus 8, and is able to infect multiple cell lines, including those of human origin. Using next-generation sequencing technology, the authors constructed a full-length annotated genomic map of BGHV8. Phylogenetic analysis of several genes from BGHV8 revealed similarity to several mammalian gammaherpesviruses, including Kaposi’s sarcoma-associated herpesvirus (KSHV).",2016 Feb 17,"['Host, Kurtis M.', 'Damania, Blossom']",mSphere,,,True
6b58f76c98afb6435969ef4d9f9a063058265b98,PMC,Isolation and Characterization of a Novel Gammaherpesvirus from a Microbat Cell Line,http://dx.doi.org/10.1128/mSphere.00070-15,PMC4863610,27303702,CC BY,"While employing deep sequencing and de novo assembly to characterize the mRNA transcript profile of a cell line derived from the microbat Myotis velifer incautus, we serendipitously identified mRNAs encoding proteins with a high level of identity to herpesviruses. A majority were closely related to proteins of equine herpesvirus 2 (EHV-2), a horse gammaherpesvirus. We demonstrated by electron microscopy the presence of herpesvirus-like particles in the microbat cells. Passage of supernatants from microbat cells to Vero cells resulted in syncytium formation, and expression of viral genes and amplification of viral DNA were demonstrated by quantitative PCR. Susceptibility of human cell lines to productive infection was also demonstrated. Next-generation sequencing and de novo assembly of the viral genome from supernatants from Vero cells yielded a single contig of approximately 130 kb with at least 77 open reading frames (ORFs), predicted microRNAs (miRNAs), and a gammaherpesvirus genomic organization. Phylogenic analysis of the envelope glycoprotein (gB) and DNA polymerase (POLD1) revealed similarity to multiple gammaherpesviruses, including those from as-yet-uncultured viruses of the Rhadinovirus genus that were obtained by deep sequencing of bat tissues. Moreover, the assembled genome revealed ORFs that share little or no homology to known ORFs in EHV-2 but are similar to accessory proteins of other gammaherpesviruses. Some also have striking homology to predicted Myotis bat proteins. Cumulatively, this study provides the first isolation and characterization of a replication-competent bat gammaherpesvirus. IMPORTANCE Bats are of significant interest as reservoirs for zoonotic viral pathogens; however, tools to dissect bat-virus interactions are limited in availability. This study serendipitously identified, in an established bat cell line, a fully replication-competent gammaherpesvirus; determined the complete genome sequence of the virus; and generated a viral transcript map. This virus can replicate in select human and nonhuman primate cell lines. However, analyses of viral sequences support a bat origin for this virus; we therefore refer to the virus as bat gammaherpesvirus 8 (BGHV8). The viral genome contains unique open reading frames that likely encode modulators of bat innate and adaptive immune signaling pathways and expresses viral miRNAs. The virus and its gene products should provide a unique tool to dissect both bat and gammaherpesvirus biology.",2016 Feb 17,"['Shabman, Reed S.', 'Shrivastava, Susmita', 'Tsibane, Tshidi', 'Attie, Oliver', 'Jayaprakash, Anitha', 'Mire, Chad E.', 'Dilley, Kari E.', 'Puri, Vinita', 'Stockwell, Timothy B.', 'Geisbert, Thomas W.', 'Sachidanandam, Ravi', 'Basler, Christopher F.']",mSphere,,,True
e6e00bfca850f42e1b2baa9ce190d37554f4a42e,PMC,Genome Sequencing and Analysis of Catopsilia pomona nucleopolyhedrovirus: A Distinct Species in Group I Alphabaculovirus,http://dx.doi.org/10.1371/journal.pone.0155134,PMC4864199,27166956,CC BY,"The genome sequence of Catopsilia pomona nucleopolyhedrovirus (CapoNPV) was determined by the Roche 454 sequencing system. The genome consisted of 128,058 bp and had an overall G+C content of 40%. There were 130 hypothetical open reading frames (ORFs) potentially encoding proteins of more than 50 amino acids and covering 92% of the genome. Among all the hypothetical ORFs, 37 baculovirus core genes, 23 lepidopteran baculovirus conserved genes and 10 genes conserved in Group I alphabaculoviruses were identified. In addition, the genome included regions of 8 typical baculoviral homologous repeat sequences (hrs). Phylogenic analysis showed that CapoNPV was in a distinct branch of clade “a” in Group I alphabaculoviruses. Gene parity plot analysis and overall similarity of ORFs indicated that CapoNPV is more closely related to the Group I alphabaculoviruses than to other baculoviruses. Interesting, CapoNPV lacks the genes encoding the fibroblast growth factor (fgf) and ac30, which are conserved in most lepidopteran and Group I baculoviruses, respectively. Sequence analysis of the F-like protein of CapoNPV showed that some amino acids were inserted into the fusion peptide region and the pre-transmembrane region of the protein. All these unique features imply that CapoNPV represents a member of a new baculovirus species.",2016 May 11,"['Wang, Jun', 'Zhu, Zheng', 'Zhang, Lei', 'Hou, Dianhai', 'Wang, Manli', 'Arif, Basil', 'Kou, Zheng', 'Wang, Hualin', 'Deng, Fei', 'Hu, Zhihong']",PLoS One,,,True
345a04a8633d593b5a400b559d533a6b4595f490,PMC,Comparative Transcriptome Analysis of Bombyx mori (Lepidoptera) Larval Midgut Response to BmNPV in Susceptible and Near-Isogenic Resistant Strains,http://dx.doi.org/10.1371/journal.pone.0155341,PMC4864234,27168061,CC BY,"Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the primary pathogens causing severe economic losses in sericulture. However, the molecular mechanism of silkworm resistance to BmNPV remains largely unknown. Here, the recurrent parent P50 (susceptible strain) and the near-isogenic line BC9 (resistance strain) were used in a comparative transcriptome study examining the response to infection with BmNPV. A total of 14,300 unigenes were obtained from two different resistant strains; of these, 869 differentially expressed genes (DEGs) were identified after comparing the four transcriptomes. Many DEGs associated with protein metabolism, cytoskeleton, and apoptosis may be involved in the host response to BmNPV infection. Moreover, some immunity related genes were also altered following BmNPV infection. Specifically, after removing genetic background and individual immune stress response genes, 22 genes were found to be potentially involved in repressing BmNPV infection. These genes were related to transport, virus replication, intracellular innate immune, and apoptosis. Our study provided an overview of the molecular mechanism of silkworm resistance to BmNPV infection and laid a foundation for controlling BmNPV in the future.",2016 May 11,"['Wang, Xue-Yang', 'Yu, Hai-Zhong', 'Geng, Lei', 'Xu, Jia-Ping', 'Yu, Dong', 'Zhang, Shang-Zhi', 'Ma, Yan', 'Fei, Dong-Qiong']",PLoS One,,,True
9da90a751f76421e3069d40bd2eae1891f778965,PMC,Correction: Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor,http://dx.doi.org/10.1371/journal.ppat.1005650,PMC4864313,27166862,CC BY,,2016 May 11,"['Kim, Yunjeong', 'Liu, Hongwei', 'Kankanamalage, Anushka C. Galasiti', 'Weerasekara, Sahani', 'Hua, Duy H.', 'Groutas, William C.', 'Chang, Kyeong-Ok', 'Pedersen, Niels C.']",PLoS Pathog,,,False
87d031191cd30614cfded9fbea64d0a4db44952a,PMC,Neurological Complications of Middle East Respiratory Syndrome Coronavirus: A Report of Two Cases and Review of the Literature,http://dx.doi.org/10.1155/2016/3502683,PMC4864560,27239356,CC BY,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was first discovered in September 2012 in Saudi Arabia. Since then, it caused more than 1600 laboratory-confirmed cases and more than 580 deaths among them. The clinical course of the disease ranges from asymptomatic infection to severe lower respiratory tract illness with multiorgan involvement and death. The disease can cause pulmonary, renal, hematological, and gastrointestinal complications. In this paper, we report neurological complications of MERS-CoV in two adult patients, and we hypothesize the pathophysiology. The first patient had an intracerebral hemorrhage as a result of thrombocytopenia, disseminated intravascular coagulation, and platelet dysfunction. The second case was a case of critical illness polyneuropathy complicating a long ICU stay. In these cases, the neurological complications were secondary to systemic complications and long ICU stay. Autopsy studies are needed to further understand the pathological mechanism.",2016 Apr 28,"['Algahtani, Hussein', 'Subahi, Ahmad', 'Shirah, Bader']",Case Rep Neurol Med,,,True
530fba50d0d6378e080e760093969b0b3b9c479d,PMC,Influence of the Pressure Difference and Door Swing on Heavy Contaminants Migration between Rooms,http://dx.doi.org/10.1371/journal.pone.0155159,PMC4865048,27171260,CC BY,"This paper presents the results of investigations whose aim was to describe the influence of the pressure difference level on the ability of contaminants migration between neighbouring rooms in dynamic conditions associated with door swing. The analysis was based on airflow visualization made with cold smoke, which simulated the heavy contaminants. The test room was pressurized to a specific level and then the door was opened to observe the trail of the smoke plume in the plane of the door. The door was opened in both directions: to the positively and negatively pressurized room. This study focuses on the visualization of smoke plume discharge and an uncertainty analysis is not applicable. Unlike other studies which focus on the analysis of pressure difference, the present study looks at the contaminants which are heavier than air and on “pumping out” the contaminants by means of door swing. Setting the proper level of pressure difference between the contaminated room and the neighbouring rooms can prove instrumental in ensuring protection against toxic contaminants migration. This study helped to establish the threshold of pressure difference necessary to reduce migration of heavy contaminants to neighbouring rooms.",2016 May 12,"['Hendiger, Jacek', 'Chludzińska, Marta', 'Ziętek, Piotr']",PLoS One,,,True
8e875cc9628872c52aea9d9c298e1b87cf82f1e7,PMC,"The Role of Human Coronaviruses in Children Hospitalized for Acute Bronchiolitis, Acute Gastroenteritis, and Febrile Seizures: A 2-Year Prospective Study",http://dx.doi.org/10.1371/journal.pone.0155555,PMC4865086,27171141,CC BY,"Human coronaviruses (HCoVs) are associated with a variety of clinical presentations in children, but their role in disease remains uncertain. The objective of our prospective study was to investigate HCoVs associations with various clinical presentations in hospitalized children up to 6 years of age. Children hospitalized with acute bronchiolitis (AB), acute gastroenteritis (AGE), or febrile seizures (FS), and children admitted for elective surgical procedures (healthy controls) were included in the study. In patients with AB, AGE, and FS, a nasopharyngeal (NP) swab and blood sample were obtained upon admission and the follow-up visit 14 days later, whereas in children with AGE a stool sample was also acquired upon admission; in healthy controls a NP swab and stool sample were taken upon admission. Amplification of polymerase 1b gene was used to detect HCoVs in the specimens. HCoVs-positive specimens were also examined for the presence of several other viruses. HCoVs were most often detected in children with FS (19/192, 9.9%, 95% CI: 6–15%), followed by children with AGE (19/218, 8.7%, 95% CI: 5.3–13.3%) and AB (20/308, 6.5%, 95% CI: 4.0–9.8%). The presence of other viruses was a common finding, most frequent in the group of children with AB (19/20, 95%, 95% CI: 75.1–99.8%), followed by FS (10/19, 52.6%, 95% CI: 28.9–75.6%) and AGE (7/19, 36.8%, 95% CI: 16.3–61.6%). In healthy control children HCoVs were detected in 3/156 (1.9%, 95% CI: 0.4–5.5%) NP swabs and 1/150 (0.7%, 95% CI: 0.02–3.3%) stool samples. It seems that an etiological role of HCoVs is most likely in children with FS, considering that they had a higher proportion of positive HCoVs results than patients with AB and those with AGE, and had the highest viral load; however, the co-detection of other viruses was 52.6%. Trial Registration: ClinicalTrials.gov NCT00987519",2016 May 12,"['Jevšnik, Monika', 'Steyer, Andrej', 'Pokorn, Marko', 'Mrvič, Tatjana', 'Grosek, Štefan', 'Strle, Franc', 'Lusa, Lara', 'Petrovec, Miroslav']",PLoS One,,,True
abc8ce495c2a97f9b53e0b2b25a33adcf73de797,PMC,"The Role of Human Coronaviruses in Children Hospitalized for Acute Bronchiolitis, Acute Gastroenteritis, and Febrile Seizures: A 2-Year Prospective Study",http://dx.doi.org/10.1371/journal.pone.0155555,PMC4865086,27171141,CC BY,"Human coronaviruses (HCoVs) are associated with a variety of clinical presentations in children, but their role in disease remains uncertain. The objective of our prospective study was to investigate HCoVs associations with various clinical presentations in hospitalized children up to 6 years of age. Children hospitalized with acute bronchiolitis (AB), acute gastroenteritis (AGE), or febrile seizures (FS), and children admitted for elective surgical procedures (healthy controls) were included in the study. In patients with AB, AGE, and FS, a nasopharyngeal (NP) swab and blood sample were obtained upon admission and the follow-up visit 14 days later, whereas in children with AGE a stool sample was also acquired upon admission; in healthy controls a NP swab and stool sample were taken upon admission. Amplification of polymerase 1b gene was used to detect HCoVs in the specimens. HCoVs-positive specimens were also examined for the presence of several other viruses. HCoVs were most often detected in children with FS (19/192, 9.9%, 95% CI: 6–15%), followed by children with AGE (19/218, 8.7%, 95% CI: 5.3–13.3%) and AB (20/308, 6.5%, 95% CI: 4.0–9.8%). The presence of other viruses was a common finding, most frequent in the group of children with AB (19/20, 95%, 95% CI: 75.1–99.8%), followed by FS (10/19, 52.6%, 95% CI: 28.9–75.6%) and AGE (7/19, 36.8%, 95% CI: 16.3–61.6%). In healthy control children HCoVs were detected in 3/156 (1.9%, 95% CI: 0.4–5.5%) NP swabs and 1/150 (0.7%, 95% CI: 0.02–3.3%) stool samples. It seems that an etiological role of HCoVs is most likely in children with FS, considering that they had a higher proportion of positive HCoVs results than patients with AB and those with AGE, and had the highest viral load; however, the co-detection of other viruses was 52.6%. Trial Registration: ClinicalTrials.gov NCT00987519",2016 May 12,"['Jevšnik, Monika', 'Steyer, Andrej', 'Pokorn, Marko', 'Mrvič, Tatjana', 'Grosek, Štefan', 'Strle, Franc', 'Lusa, Lara', 'Petrovec, Miroslav']",PLoS One,,,False
d1fd684938b2d4358d1fde27a474bf71df02287b,PMC,Cytokine Profiles in Human Metapneumovirus Infected Children: Identification of Genes Involved in the Antiviral Response and Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0155484,PMC4865088,27171557,CC BY,"Human metapneumovirus (hMPV) causes severe airway infection in children that may be caused by an unfavorable immune response. The nature of the innate immune response to hMPV in naturally occurring infections in children is largely undescribed, and it is unknown if inflammasome activation is implicated in disease pathogenesis. We examined nasopharynx aspirates and blood samples from hMPV-infected children without detectable co-infections. The expression of inflammatory and antiviral genes were measured in nasal airway secretions by relative mRNA quantification while blood plasma proteins were determined by a multiplex immunoassay. Several genes were significantly up-regulated at mRNA and protein level in the hMPV infected children. Most apparent was the expression of the chemokine IP-10, the pro-inflammatory cytokine IL-18 in addition to the interferon inducible gene ISG54. Interestingly, children experiencing more severe disease, as indicated by a severity index, had significantly more often up-regulation of the inflammasome-associated genes IL-1β and NLRP3. Overall, our data point to cytokines, particularly inflammasome-associated, that might be important in hMPV mediated lung disease and the antiviral response in children with severe infection. Our study is the first to demonstrate that inflammasome components are associated with increased illness severity in hMPV-infected children.",2016 May 12,"['Malmo, Jostein', 'Moe, Nina', 'Krokstad, Sidsel', 'Ryan, Liv', 'Loevenich, Simon', 'Johnsen, Ingvild B.', 'Espevik, Terje', 'Nordbø, Svein Arne', 'Døllner, Henrik', 'Anthonsen, Marit W.']",PLoS One,,,True
ffe663e4ef5018da41f057533520b9d85ec86e18,PMC,Global Variability in Reported Mortality for Critical Illness during the 2009-10 Influenza A(H1N1) Pandemic: A Systematic Review and Meta-Regression to Guide Reporting of Outcomes during Disease Outbreaks,http://dx.doi.org/10.1371/journal.pone.0155044,PMC4865181,27170999,CC BY,"PURPOSE: To determine how patient, healthcare system and study-specific factors influence reported mortality associated with critical illness during the 2009–2010 Influenza A (H1N1) pandemic. METHODS: Systematic review with meta-regression of studies reporting on mortality associated with critical illness during the 2009–2010 Influenza A (H1N1) pandemic. DATA SOURCES: Medline, Embase, LiLACs and African Index Medicus to June 2009-March 2016. RESULTS: 226 studies from 50 countries met our inclusion criteria. Mortality associated with H1N1-related critical illness was 31% (95% CI 28–34). Reported mortality was highest in South Asia (61% [95% CI 50–71]) and Sub-Saharan Africa (53% [95% CI 29–75]), in comparison to Western Europe (25% [95% CI 22–30]), North America (25% [95% CI 22–27]) and Australia (15% [95% CI 13–18]) (P<0.0001). High income economies had significantly lower reported mortality compared to upper middle income economies and lower middle income economies respectively (P<0.0001). Mortality for the first wave was non-significantly higher than wave two (P = 0.66). There was substantial variability in reported mortality among the specific subgroups of patients: unselected critically ill adults (27% [95% CI 24–30]), acute respiratory distress syndrome (37% [95% CI 32–44]), acute kidney injury (44% [95% CI 26–64]), and critically ill pregnant patients (10% [95% CI 5–19]). CONCLUSION: Reported mortality for outbreaks and pandemics may vary substantially depending upon selected patient characteristics, the number of patients described, and the region and economic status of the outbreak location. Outcomes from a relatively small number of patients from specific regions may lead to biased estimates of outcomes on a global scale.",2016 May 12,"['Duggal, Abhijit', 'Pinto, Ruxandra', 'Rubenfeld, Gordon', 'Fowler, Robert A.']",PLoS One,,,True
646d3092d14896e26c741391f0b5fe5b724f4a39,PMC,Rice endosperm is cost‐effective for the production of recombinant griffithsin with potent activity against HIV,http://dx.doi.org/10.1111/pbi.12507,PMC4865440,26800650,CC BY,"Protein microbicides containing neutralizing antibodies and antiviral lectins may help to reduce the rate of infection with human immunodeficiency virus (HIV) if it is possible to manufacture the components in large quantities at a cost affordable in HIV‐endemic regions such as sub‐Saharan Africa. We expressed the antiviral lectin griffithsin (GRFT), which shows potent neutralizing activity against HIV, in the endosperm of transgenic rice plants (Oryza sativa), to determine whether rice can be used to produce inexpensive GRFT as a microbicide ingredient. The yield of (OS)GRFT in the best‐performing plants was 223 μg/g dry seed weight. We also established a one‐step purification protocol, achieving a recovery of 74% and a purity of 80%, which potentially could be developed into a larger‐scale process to facilitate inexpensive downstream processing. (OS)GRFT bound to HIV glycans with similar efficiency to GRFT produced in Escherichia coli. Whole‐cell assays using purified (OS)GRFT and infectivity assays using crude extracts of transgenic rice endosperm confirmed that both crude and pure (OS)GRFT showed potent activity against HIV and the crude extracts were not toxic towards human cell lines, suggesting they could be administered as a microbicide with only minimal processing. A freedom‐to‐operate analysis confirmed that GRFT produced in rice is suitable for commercial development, and an economic evaluation suggested that 1.8 kg/ha of pure GRFT could be produced from rice seeds. Our data therefore indicate that rice could be developed as an inexpensive production platform for GRFT as a microbicide component.",2016 Jun 23,"['Vamvaka, Evangelia', 'Arcalis, Elsa', 'Ramessar, Koreen', 'Evans, Abbey', ""O'Keefe, Barry R."", 'Shattock, Robin J.', 'Medina, Vicente', 'Stöger, Eva', 'Christou, Paul', 'Capell, Teresa']",Plant Biotechnol J,,,True
a6176cded64c46ece2d4cef65ffdf638f4adceba,PMC,Strategies for Human Tumor Virus Discoveries: From Microscopic Observation to Digital Transcriptome Subtraction,http://dx.doi.org/10.3389/fmicb.2016.00676,PMC4865503,27242703,CC BY,"Over 20% of human cancers worldwide are associated with infectious agents, including viruses, bacteria, and parasites. Various methods have been used to identify human tumor viruses, including electron microscopic observations of viral particles, immunologic screening, cDNA library screening, nucleic acid hybridization, consensus PCR, viral DNA array chip, and representational difference analysis. With the Human Genome Project, a large amount of genetic information from humans and other organisms has accumulated over the last decade. Utilizing the available genetic databases, Feng et al. (2007) developed digital transcriptome subtraction (DTS), an in silico method to sequentially subtract human sequences from tissue or cellular transcriptome, and discovered Merkel cell polyomavirus (MCV) from Merkel cell carcinoma. Here, we review the background and methods underlying the human tumor virus discoveries and explain how DTS was developed and used for the discovery of MCV.",2016 May 13,"['Mirvish, Ezra D.', 'Shuda, Masahiro']",Front Microbiol,,,True
222534164391422210b3089109605e8ff4d1d46c,PMC,SARS coronavirus papain-like protease induces Egr-1-dependent up-regulation of TGF-β1 via ROS/p38 MAPK/STAT3 pathway,http://dx.doi.org/10.1038/srep25754,PMC4865725,27173006,CC BY,"SARS coronavirus (SARS-CoV) papain-like protease (PLpro) has been identified in TGF-β1 up-regulation in human promonocytes (Proteomics 2012, 12: 3193-205). This study investigates the mechanisms of SARS-CoV PLpro-induced TGF-β1 promoter activation in human lung epithelial cells and mouse models. SARS-CoV PLpro dose- and time-dependently up-regulates TGF-β1 and vimentin in A549 cells. Dual luciferase reporter assays with TGF-β1 promoter plasmids indicated that TGF-β1 promoter region between −175 to −60, the Egr-1 binding site, was responsible for TGF-β1 promoter activation induced by SARS-CoV PLpro. Subcellular localization analysis of transcription factors showed PLpro triggering nuclear translocation of Egr-1, but not NF-κB and Sp-1. Meanwhile, Egr-1 silencing by siRNA significantly reduced PLpro-induced up-regulation of TGF-β1, TSP-1 and pro-fibrotic genes. Furthermore, the inhibitors for ROS (YCG063), p38 MAPK (SB203580), and STAT3 (Stattic) revealed ROS/p38 MAPK/STAT3 pathway involving in Egr-1 dependent activation of TGF-β1 promoter induced by PLpro. In a mouse model with a direct pulmonary injection, PLpro stimulated macrophage infiltration into lung, up-regulating Egr-1, TSP-1, TGF-β1 and vimentin expression in lung tissues. The results revealed that SARS-CoV PLpro significantly triggered Egr-1 dependent activation of TGF-β1 promoter via ROS/p38 MAPK/STAT3 pathway, correlating with up-regulation of pro-fibrotic responses in vitro and in vivo.",2016 May 13,"['Li, Shih-Wein', 'Wang, Ching-Ying', 'Jou, Yu-Jen', 'Yang, Tsuey-Ching', 'Huang, Su-Hua', 'Wan, Lei', 'Lin, Ying-Ju', 'Lin, Cheng-Wen']",Sci Rep,,,True
479b22be77d8770d98513f73d21841020e7a9cbe,PMC,SARS coronavirus papain-like protease induces Egr-1-dependent up-regulation of TGF-β1 via ROS/p38 MAPK/STAT3 pathway,http://dx.doi.org/10.1038/srep25754,PMC4865725,27173006,CC BY,"SARS coronavirus (SARS-CoV) papain-like protease (PLpro) has been identified in TGF-β1 up-regulation in human promonocytes (Proteomics 2012, 12: 3193-205). This study investigates the mechanisms of SARS-CoV PLpro-induced TGF-β1 promoter activation in human lung epithelial cells and mouse models. SARS-CoV PLpro dose- and time-dependently up-regulates TGF-β1 and vimentin in A549 cells. Dual luciferase reporter assays with TGF-β1 promoter plasmids indicated that TGF-β1 promoter region between −175 to −60, the Egr-1 binding site, was responsible for TGF-β1 promoter activation induced by SARS-CoV PLpro. Subcellular localization analysis of transcription factors showed PLpro triggering nuclear translocation of Egr-1, but not NF-κB and Sp-1. Meanwhile, Egr-1 silencing by siRNA significantly reduced PLpro-induced up-regulation of TGF-β1, TSP-1 and pro-fibrotic genes. Furthermore, the inhibitors for ROS (YCG063), p38 MAPK (SB203580), and STAT3 (Stattic) revealed ROS/p38 MAPK/STAT3 pathway involving in Egr-1 dependent activation of TGF-β1 promoter induced by PLpro. In a mouse model with a direct pulmonary injection, PLpro stimulated macrophage infiltration into lung, up-regulating Egr-1, TSP-1, TGF-β1 and vimentin expression in lung tissues. The results revealed that SARS-CoV PLpro significantly triggered Egr-1 dependent activation of TGF-β1 promoter via ROS/p38 MAPK/STAT3 pathway, correlating with up-regulation of pro-fibrotic responses in vitro and in vivo.",2016 May 13,"['Li, Shih-Wein', 'Wang, Ching-Ying', 'Jou, Yu-Jen', 'Yang, Tsuey-Ching', 'Huang, Su-Hua', 'Wan, Lei', 'Lin, Ying-Ju', 'Lin, Cheng-Wen']",Sci Rep,,,False
afac5482c4fb73ba67db7127e3d0c9ed19882c35,PMC,An RNA-dependent RNA polymerase gene in bat genomes derived from an ancient negative-strand RNA virus,http://dx.doi.org/10.1038/srep25873,PMC4865735,27174689,CC BY,"Endogenous bornavirus-like L (EBLL) elements are inheritable sequences derived from ancient bornavirus L genes that encode a viral RNA-dependent RNA polymerase (RdRp) in many eukaryotic genomes. Here, we demonstrate that bats of the genus Eptesicus have preserved for more than 11.8 million years an EBLL element named eEBLL-1, which has an intact open reading frame of 1,718 codons. The eEBLL-1 coding sequence revealed that functional motifs essential for mononegaviral RdRp activity are well conserved in the EBLL-1 genes. Genetic analyses showed that natural selection operated on eEBLL-1 during the evolution of Eptesicus. Notably, we detected efficient transcription of eEBLL-1 in tissues from Eptesicus bats. To the best of our knowledge, this study is the first report showing that the eukaryotic genome has gained a riboviral polymerase gene from an ancient virus that has the potential to encode a functional RdRp.",2016 May 13,"['Horie, Masayuki', 'Kobayashi, Yuki', 'Honda, Tomoyuki', 'Fujino, Kan', 'Akasaka, Takumi', 'Kohl, Claudia', 'Wibbelt, Gudrun', 'Mühldorfer, Kristin', 'Kurth, Andreas', 'Müller, Marcel A.', 'Corman, Victor M.', 'Gillich, Nadine', 'Suzuki, Yoshiyuki', 'Schwemmle, Martin', 'Tomonaga, Keizo']",Sci Rep,,,True
4d17dcfe7d1c0280f69bc876f1c6049e79e5bca0,PMC,An RNA-dependent RNA polymerase gene in bat genomes derived from an ancient negative-strand RNA virus,http://dx.doi.org/10.1038/srep25873,PMC4865735,27174689,CC BY,"Endogenous bornavirus-like L (EBLL) elements are inheritable sequences derived from ancient bornavirus L genes that encode a viral RNA-dependent RNA polymerase (RdRp) in many eukaryotic genomes. Here, we demonstrate that bats of the genus Eptesicus have preserved for more than 11.8 million years an EBLL element named eEBLL-1, which has an intact open reading frame of 1,718 codons. The eEBLL-1 coding sequence revealed that functional motifs essential for mononegaviral RdRp activity are well conserved in the EBLL-1 genes. Genetic analyses showed that natural selection operated on eEBLL-1 during the evolution of Eptesicus. Notably, we detected efficient transcription of eEBLL-1 in tissues from Eptesicus bats. To the best of our knowledge, this study is the first report showing that the eukaryotic genome has gained a riboviral polymerase gene from an ancient virus that has the potential to encode a functional RdRp.",2016 May 13,"['Horie, Masayuki', 'Kobayashi, Yuki', 'Honda, Tomoyuki', 'Fujino, Kan', 'Akasaka, Takumi', 'Kohl, Claudia', 'Wibbelt, Gudrun', 'Mühldorfer, Kristin', 'Kurth, Andreas', 'Müller, Marcel A.', 'Corman, Victor M.', 'Gillich, Nadine', 'Suzuki, Yoshiyuki', 'Schwemmle, Martin', 'Tomonaga, Keizo']",Sci Rep,,,False
9671b5d479956e73b3f749873f672dd421019b80,PMC,An RNA-dependent RNA polymerase gene in bat genomes derived from an ancient negative-strand RNA virus,http://dx.doi.org/10.1038/srep25873,PMC4865735,27174689,CC BY,"Endogenous bornavirus-like L (EBLL) elements are inheritable sequences derived from ancient bornavirus L genes that encode a viral RNA-dependent RNA polymerase (RdRp) in many eukaryotic genomes. Here, we demonstrate that bats of the genus Eptesicus have preserved for more than 11.8 million years an EBLL element named eEBLL-1, which has an intact open reading frame of 1,718 codons. The eEBLL-1 coding sequence revealed that functional motifs essential for mononegaviral RdRp activity are well conserved in the EBLL-1 genes. Genetic analyses showed that natural selection operated on eEBLL-1 during the evolution of Eptesicus. Notably, we detected efficient transcription of eEBLL-1 in tissues from Eptesicus bats. To the best of our knowledge, this study is the first report showing that the eukaryotic genome has gained a riboviral polymerase gene from an ancient virus that has the potential to encode a functional RdRp.",2016 May 13,"['Horie, Masayuki', 'Kobayashi, Yuki', 'Honda, Tomoyuki', 'Fujino, Kan', 'Akasaka, Takumi', 'Kohl, Claudia', 'Wibbelt, Gudrun', 'Mühldorfer, Kristin', 'Kurth, Andreas', 'Müller, Marcel A.', 'Corman, Victor M.', 'Gillich, Nadine', 'Suzuki, Yoshiyuki', 'Schwemmle, Martin', 'Tomonaga, Keizo']",Sci Rep,,,False
413383034f00fe7c2c81688ac152dc102963d08b,PMC,Targeted next-generation sequencing for the detection of ciprofloxacin resistance markers using molecular inversion probes,http://dx.doi.org/10.1038/srep25904,PMC4865750,27174456,CC BY,"Antibiotic resistance (AR) is an epidemic of increasing magnitude requiring rapid identification and profiling for appropriate and timely therapeutic measures and containment strategies. In this context, ciprofloxacin is part of the first-line of countermeasures against numerous high consequence bacteria. Significant resistance can occur via single nucleotide polymorphisms (SNP) and deletions within ciprofloxacin targeted genes. Ideally, use of ciprofloxacin would be prefaced with AR determination to avoid overuse or misuse of the antibiotic. Here, we describe the development and evaluation of a panel of 44 single-stranded molecular inversion probes (MIPs) coupled to next-generation sequencing (NGS) for the detection of genetic variants known to confer ciprofloxacin resistance in Bacillus anthracis, Yersinia pestis, and Francisella tularensis. Sequencing results demonstrate MIPs capture and amplify targeted regions of interest at significant levels of coverage. Depending on the genetic variant, limits of detection (LOD) for high-throughput pooled sequencing ranged from approximately 300–1800 input genome copies. LODs increased 10-fold in the presence of contaminating human genome DNA. In addition, we show that MIPs can be used as an enrichment step with high resolution melt (HRM) real-time PCR which is a sensitive assay with a rapid time-to-answer. Overall, this technology is a multiplexable upfront enrichment applicable with multiple downstream molecular assays for the detection of targeted genetic regions.",2016 May 13,"['Stefan, Christopher P.', 'Koehler, Jeffrey W.', 'Minogue, Timothy D.']",Sci Rep,,,True
61bf04a5d7173cec5cbd4fbb977deeaf09e2c678,PMC,Targeted next-generation sequencing for the detection of ciprofloxacin resistance markers using molecular inversion probes,http://dx.doi.org/10.1038/srep25904,PMC4865750,27174456,CC BY,"Antibiotic resistance (AR) is an epidemic of increasing magnitude requiring rapid identification and profiling for appropriate and timely therapeutic measures and containment strategies. In this context, ciprofloxacin is part of the first-line of countermeasures against numerous high consequence bacteria. Significant resistance can occur via single nucleotide polymorphisms (SNP) and deletions within ciprofloxacin targeted genes. Ideally, use of ciprofloxacin would be prefaced with AR determination to avoid overuse or misuse of the antibiotic. Here, we describe the development and evaluation of a panel of 44 single-stranded molecular inversion probes (MIPs) coupled to next-generation sequencing (NGS) for the detection of genetic variants known to confer ciprofloxacin resistance in Bacillus anthracis, Yersinia pestis, and Francisella tularensis. Sequencing results demonstrate MIPs capture and amplify targeted regions of interest at significant levels of coverage. Depending on the genetic variant, limits of detection (LOD) for high-throughput pooled sequencing ranged from approximately 300–1800 input genome copies. LODs increased 10-fold in the presence of contaminating human genome DNA. In addition, we show that MIPs can be used as an enrichment step with high resolution melt (HRM) real-time PCR which is a sensitive assay with a rapid time-to-answer. Overall, this technology is a multiplexable upfront enrichment applicable with multiple downstream molecular assays for the detection of targeted genetic regions.",2016 May 13,"['Stefan, Christopher P.', 'Koehler, Jeffrey W.', 'Minogue, Timothy D.']",Sci Rep,,,False
7d5cd4faf19ae8838653aa65ea172c97f8bfe9f4,PMC,X-Ray Structure and Inhibition of 3C-like Protease from Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.1038/srep25961,PMC4865815,27173881,CC BY,"Porcine epidemic diarrhea virus (PEDV) is a coronavirus that infects pigs and can have mortality rates approaching 100% in piglets, causing serious economic impact. The 3C-like protease (3CL(pro)) is essential for the coronaviral life cycle and is an appealing target for the development of therapeutics. We report the expression, purification, crystallization and 2.10 Å X-ray structure of 3CL(pro) from PEDV. Analysis of the PEDV 3CL(pro) structure and comparison to other coronaviral 3CL(pro)’s from the same alpha-coronavirus phylogeny shows that the overall structures and active site architectures across 3CL(pro)’s are conserved, with the exception of a loop that comprises the protease S(2) pocket. We found a known inhibitor of severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL(pro), (R)-16, to have inhibitor activity against PEDV 3CL(pro), despite that SARS-3CL(pro) and PEDV 3CL(pro) share only 45.4% sequence identity. Structural comparison reveals that the majority of residues involved in (R)-16 binding to SARS-3CL(pro) are conserved in PEDV-3CL(pro); however, the sequence variation and positional difference in the loop forming the S(2) pocket may account for large observed difference in IC(50) values. This work advances our understanding of the subtle, but important, differences in coronaviral 3CL(pro) architecture and contributes to the broader structural knowledge of coronaviral 3CL(pro)’s.",2016 May 13,"['St. John, Sarah E.', 'Anson, Brandon J.', 'Mesecar, Andrew D.']",Sci Rep,,,True
bf114390000199ac4f7c1f1f07c3320f0cb38657,PMC,Potent neutralizing monoclonal antibodies against Ebola virus infection,http://dx.doi.org/10.1038/srep25856,PMC4867612,27181584,CC BY,"Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection.",2016 May 16,"['Zhang, Qi', 'Gui, Miao', 'Niu, Xuefeng', 'He, Shihua', 'Wang, Ruoke', 'Feng, Yupeng', 'Kroeker, Andrea', 'Zuo, Yanan', 'Wang, Hua', 'Wang, Ying', 'Li, Jiade', 'Li, Chufang', 'Shi, Yi', 'Shi, Xuanling', 'Gao, George F.', 'Xiang, Ye', 'Qiu, Xiangguo', 'Chen, Ling', 'Zhang, Linqi']",Sci Rep,,,True
db141d655abc3f86c6754e91cf00b56307124194,PMC,Potent neutralizing monoclonal antibodies against Ebola virus infection,http://dx.doi.org/10.1038/srep25856,PMC4867612,27181584,CC BY,"Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection.",2016 May 16,"['Zhang, Qi', 'Gui, Miao', 'Niu, Xuefeng', 'He, Shihua', 'Wang, Ruoke', 'Feng, Yupeng', 'Kroeker, Andrea', 'Zuo, Yanan', 'Wang, Hua', 'Wang, Ying', 'Li, Jiade', 'Li, Chufang', 'Shi, Yi', 'Shi, Xuanling', 'Gao, George F.', 'Xiang, Ye', 'Qiu, Xiangguo', 'Chen, Ling', 'Zhang, Linqi']",Sci Rep,,,False
6039b17b00ec8948aa66da30a1164ed9634e3ceb,PMC,Surveillance and response systems for elimination of tropical diseases: summary of a thematic series in Infectious Diseases of Poverty,http://dx.doi.org/10.1186/s40249-016-0144-7,PMC4868018,27179509,CC BY,"The peer-reviewed journal Infectious Diseases of Poverty provides a new platform to engage with, and disseminate in an open-access format, science outside traditional disciplinary boundaries. The current piece reviews a thematic series on surveillance-response systems for elimination of tropical diseases. Overall, 22 contributions covering a broad array of diseases are featured – i.e. clonorchiasis, dengue, hepatitis, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), H7N9 avian influenza, lymphatic filariasis, malaria, Middle East respiratory syndrome (MERS), rabies, schistosomiasis and tuberculosis (TB). There are five scoping reviews, a commentary, a letter to the editor, an opinion piece and an editorial pertaining to the theme “Elimination of tropical disease through surveillance and response”. The remaining 13 articles are original contributions mainly covering (i) drug resistance; (ii) innovation and validation in the field of mathematical modelling; (iii) elimination of infectious diseases; and (iv) social media reports on disease outbreak notifications released by national health authorities. Analysis of the authors’ affiliations reveals that scientists from the People’s Republic of China (P.R. China) are prominently represented. Possible explanations include the fact that the 2012 and 2014 international conferences pertaining to surveillance-response mechanisms were both hosted by the National Institute of Parasitic Diseases (NIPD) in Shanghai, coupled with P.R. China’s growing importance with regard to the control of infectious diseases. Within 4 to 22 months of publication, three of the 22 contributions were viewed more than 10 000 times each. With sustained efforts focusing on relevant and strategic information towards control and elimination of infectious diseases, Infectious Diseases of Poverty has become a leading journal in the field of surveillance and response systems in infectious diseases and beyond. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0144-7) contains supplementary material, which is available to authorized users.",2016 May 14,"['Zhou, Xia', 'Yap, Peiling', 'Tanner, Marcel', 'Bergquist, Robert', 'Utzinger, Jürg', 'Zhou, Xiao-Nong']",Infect Dis Poverty,,,False
17787dbfbb012b537726971936c74cab0aa701b1,PMC,Surveillance and response systems for elimination of tropical diseases: summary of a thematic series in Infectious Diseases of Poverty,http://dx.doi.org/10.1186/s40249-016-0144-7,PMC4868018,27179509,CC BY,"The peer-reviewed journal Infectious Diseases of Poverty provides a new platform to engage with, and disseminate in an open-access format, science outside traditional disciplinary boundaries. The current piece reviews a thematic series on surveillance-response systems for elimination of tropical diseases. Overall, 22 contributions covering a broad array of diseases are featured – i.e. clonorchiasis, dengue, hepatitis, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), H7N9 avian influenza, lymphatic filariasis, malaria, Middle East respiratory syndrome (MERS), rabies, schistosomiasis and tuberculosis (TB). There are five scoping reviews, a commentary, a letter to the editor, an opinion piece and an editorial pertaining to the theme “Elimination of tropical disease through surveillance and response”. The remaining 13 articles are original contributions mainly covering (i) drug resistance; (ii) innovation and validation in the field of mathematical modelling; (iii) elimination of infectious diseases; and (iv) social media reports on disease outbreak notifications released by national health authorities. Analysis of the authors’ affiliations reveals that scientists from the People’s Republic of China (P.R. China) are prominently represented. Possible explanations include the fact that the 2012 and 2014 international conferences pertaining to surveillance-response mechanisms were both hosted by the National Institute of Parasitic Diseases (NIPD) in Shanghai, coupled with P.R. China’s growing importance with regard to the control of infectious diseases. Within 4 to 22 months of publication, three of the 22 contributions were viewed more than 10 000 times each. With sustained efforts focusing on relevant and strategic information towards control and elimination of infectious diseases, Infectious Diseases of Poverty has become a leading journal in the field of surveillance and response systems in infectious diseases and beyond. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0144-7) contains supplementary material, which is available to authorized users.",2016 May 14,"['Zhou, Xia', 'Yap, Peiling', 'Tanner, Marcel', 'Bergquist, Robert', 'Utzinger, Jürg', 'Zhou, Xiao-Nong']",Infect Dis Poverty,,,True
962b1eed7da37d26000eb9232c49851420b1e662,PMC,Feline Coronavirus 3c Protein: A Candidate for a Virulence Marker?,http://dx.doi.org/10.1155/2016/8560691,PMC4868892,27243037,CC BY,"Feline infectious peritonitis virus (FIPV) is highly virulent and responsible for the highly fatal disease feline infectious peritonitis (FIP), whereas feline enteric coronavirus (FECV) is widespread among the feline population and typically causes asymptomatic infections. Some candidates for genetic markers capable of differentiating these two pathotypes of a unique virus (feline coronavirus) have been proposed by several studies. In the present survey, in order to search for markers that can differentiate FECV and FIPV, several clones of the 3a–c, E, and M genes were sequenced from samples obtained from cats with or without FIP. All genes showed genetic diversity and suggested the presence of FCoV mutant spectrum capable of producing a virulent pathotype in an individual-specific way. In addition, all the feline coronavirus FIPV strains demonstrated a truncated 3c protein, and the 3c gene was the only observed pathotypic marker for FCoVs, showing that 3c gene is a candidate marker for the distinction between the two pathotypes when the mutant spectrum is taken into account.",2016 May 3,"['Hora, A. S.', 'Tonietti, P. O.', 'Taniwaki, S. A.', 'Asano, K. M.', 'Maiorka, P.', 'Richtzenhain, L. J.', 'Brandão, P. E.']",Biomed Res Int,,,True
67d137d0496d7339e302c18d693c7ec960ddf733,PMC,Moving towards a new vision: implementation of a public health policy intervention,http://dx.doi.org/10.1186/s12889-016-3056-3,PMC4869271,27185039,CC BY,"BACKGROUND: Public health systems in Canada have undergone significant policy renewal over the last decade in response to threats to the public’s health, such as severe acute respiratory syndrome. There is limited research on how public health policies have been implemented or what has influenced their implementation. This paper explores policy implementation in two exemplar public health programs -chronic disease prevention and sexually-transmitted infection prevention - in Ontario, Canada. It examines public health service providers’, managers’ and senior managements’ perspectives on the process of implementation of the Ontario Public Health Standards 2008 and factors influencing implementation. METHODS: Public health staff from six health units representing rural, remote, large and small urban settings were included. We conducted 21 focus groups and 18 interviews between 2010 (manager and staff focus groups) and 2011 (senior management interviews) involving 133 participants. Research assistants coded transcripts and researchers reviewed these; the research team discussed and resolved discrepancies. To facilitate a breadth of perspectives, several team members helped interpret the findings. An integrated knowledge translation approach was used, reflected by the inclusion of academics as well as decision-makers on the team and as co-authors. RESULTS: Front line service providers often were unaware of the new policies but managers and senior management incorporated them in operational and program planning. Some participants were involved in policy development or provided feedback prior to their launch. Implementation was influenced by many factors that aligned with Greenhalgh and colleagues’ empirically-based Diffusion of Innovations in Service Organizations Framework. Factors and related components that were most clearly linked to the OPHS policy implementation were: attributes of the innovation itself; adoption by individuals; diffusion and dissemination;the outer context – interorganizational networks and collaboration; the inner setting – implementation processes and routinization; and, linkage at the design and implementation stage. CONCLUSIONS: Multiple factors influenced public health policy implementation. Results provide empirical support for components of Greenhalgh et al’s framework and suggest two additional components – the role of external organizational collaborations and partnerships as well as planning processes in influencing implementation. These are important to consider by government and public health organizations when promoting new or revised public health policies as they evolve over time. A successful policy implementation process in Ontario has helped to move public health towards the new vision. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-016-3056-3) contains supplementary material, which is available to authorized users.",2016 May 17,"['Valaitis, Ruta', 'MacDonald, Marjorie', 'Kothari, Anita', 'O’Mara, Linda', 'Regan, Sandra', 'Garcia, John', 'Murray, Nancy', 'Manson, Heather', 'Peroff-Johnston, Nancy', 'Bursey, Gayle', 'Boyko, Jennifer']",BMC Public Health,,,True
f046ba37a3a60a90b3dbcc977182efe1672ba300,PMC,Viruses are a dominant driver of protein adaptation in mammals,http://dx.doi.org/10.7554/eLife.12469,PMC4869911,27187613,CC BY,"Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of virus-interacting proteins is unknown. Here, we analyze adaptation in ~1300 virus-interacting proteins manually curated from a set of 9900 proteins conserved in all sequenced mammalian genomes. We show that viruses (i) use the more evolutionarily constrained proteins within the cellular functions they interact with and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. We conservatively estimate that viruses have driven close to 30% of all adaptive amino acid changes in the part of the human proteome conserved within mammals. Our results suggest that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes. DOI: http://dx.doi.org/10.7554/eLife.12469.001",,"['Enard, David', 'Cai, Le', 'Gwennap, Carina', 'Petrov, Dmitri A']",eLife.; 5:e12469,,,True
9a89705854ab91a21b721dd3900a91d6332c1eaf,PMC,Imaging Axonal Degeneration and Repair in Preclinical Animal Models of Multiple Sclerosis,http://dx.doi.org/10.3389/fimmu.2016.00189,PMC4871863,27242796,CC BY,"Multiple sclerosis (MS) is a central nervous system (CNS) disease characterized by chronic neuroinflammation, demyelination, and axonal damage. Infiltration of activated lymphocytes and myeloid cells are thought to be primarily responsible for white matter damage and axonopathy. Over time, this neurologic damage manifests clinically as debilitating motor and cognitive symptoms. Existing MS therapies focus on symptom relief and delay of disease progression through reduction of neuroinflammation. However, long-term strategies to remyelinate, protect, or regenerate axons have remained elusive, posing a challenge to treating progressive forms of MS. Preclinical mouse models and techniques, such as immunohistochemistry, flow cytometry, and genomic and proteomic analysis have provided advances in our understanding of discrete time-points of pathology following disease induction. More recently, in vivo and in situ two-photon (2P) microscopy has made it possible to visualize continuous real-time cellular behavior and structural changes occurring within the CNS during neuropathology. Research utilizing 2P imaging to study axonopathy in neuroinflammatory demyelinating disease has focused on five areas: (1) axonal morphologic changes, (2) organelle transport and health, (3) relationship to inflammation, (4) neuronal excitotoxicity, and (5) regenerative therapies. 2P imaging may also be used to identify novel therapeutic targets via identification and clarification of dynamic cellular and molecular mechanisms of axonal regeneration and remyelination. Here, we review tools that have made 2P accessible for imaging neuropathologies and advances in our understanding of axonal degeneration and repair in preclinical models of demyelinating diseases.",2016 May 19,"['Yandamuri, Soumya S.', 'Lane, Thomas E.']",Front Immunol,,,True
87b2f2205b9dea38eeaeddd6e3ddbb6e45f542ae,PMC,Genome-Wide Transcriptional Profiling Reveals Two Distinct Outcomes in Central Nervous System Infections of Rabies Virus,http://dx.doi.org/10.3389/fmicb.2016.00751,PMC4871871,27242764,CC BY,"Rabies remains a major public health concern in many developing countries. The precise neuropathogenesis of rabies is unknown, though it is hypothesized to be due to neuronal death or dysfunction. Mice that received intranasal inoculation of an attenuated rabies virus (RABV) strain HEP-Flury exhibited subtle clinical signs, and eventually recovered, which is different from the fatal encephalitis caused by the virulent RABV strain CVS-11. To understand the neuropathogenesis of rabies and the mechanisms of viral clearance, we applied RNA sequencing (RNA-Seq) to compare the brain transcriptomes of normal mice vs. HEP-Flury or CVS-11 intranasally inoculated mice. Our results revealed that both RABV strains altered positively and negatively the expression levels of many host genes, including genes associated with innate and adaptive immunity, inflammation and cell death. It is found that HEP-Flury infection can activate the innate immunity earlier through the RIG-I/MDA-5 signaling, and the innate immunity pre-activated by HEP-Flury or Newcastle disease virus (NDV) infection can effectively prevent the CVS-11 to invade central nervous system (CNS), but fails to clear the CVS-11 after its entry into the CNS. In addition, following CVS-11 infection, genes implicated in cell adhesion, blood vessel morphogenesis and coagulation were mainly up-regulated, while the genes involved in synaptic transmission and ion transport were significantly down-regulated. On the other hand, several genes involved in the MHC class II-mediated antigen presentation pathway were activated to a greater extent after the HEP-Flury infection as compared with the CVS-11 infection suggesting that the collaboration of CD4(+) T cells and MHC class II-mediated antigen presentation is critical for the clearance of attenuated RABV from the CNS. The differentially regulated genes reported here are likely to include potential therapeutic targets for expanding the post-exposure treatment window for RABV infection.",2016 May 19,"['Zhang, Daiting', 'He, Feilong', 'Bi, Shuilian', 'Guo, Huixia', 'Zhang, Baoshi', 'Wu, Fan', 'Liang, Jiaqi', 'Yang, Youtian', 'Tian, Qin', 'Ju, Chunmei', 'Fan, Huiying', 'Chen, Jinding', 'Guo, Xiaofeng', 'Luo, Yongwen']",Front Microbiol,,,True
24f49539fad81e8f8b10650eb9cbfd60c8ee23f5,PMC,Functional analysis of the N-terminal basic motif of a eukaryotic satellite RNA virus capsid protein in replication and packaging,http://dx.doi.org/10.1038/srep26328,PMC4872054,27193742,CC BY,"Efficient replication and assembly of virus particles are integral to the establishment of infection. In addition to the primary role of the capsid protein (CP) in encapsidating the RNA progeny, experimental evidence on positive sense single-stranded RNA viruses suggests that the CP also regulates RNA synthesis. Here, we demonstrate that replication of Satellite tobacco mosaic virus (STMV) is controlled by the cooperative interaction between STMV CP and the helper virus (HV) Tobacco mosaic virus (TMV) replicase. We identified that the STMV CP-HV replicase interaction requires a positively charged residue at the third position (3R) in the N-terminal 13 amino acid (aa) motif. Far-Northwestern blotting showed that STMV CP promotes binding between HV-replicase and STMV RNA. An STMV CP variant having an arginine to alanine substitution at position 3 in the N-terminal 13aa motif abolished replicase-CP binding. The N-terminal 13aa motif of the CP bearing alanine substitutions for positively charged residues located at positions 5, 7, 10 and 11 are defective in packaging full-length STMV, but can package a truncated STMV RNA lacking the 3′ terminal 150 nt region. These findings provide insights into the mechanism underlying the regulation of STMV replication and packaging.",2016 May 19,"['Sivanandam, Venkatesh', 'Mathews, Deborah', 'Garmann, Rees', 'Erdemci-Tandogan, Gonca', 'Zandi, Roya', 'Rao, A. L. N.']",Sci Rep,,,True
1b8a085682d10dad4baf90417a8cbcde144cc8c9,PMC,Disease management with ARIMA model in time series,http://dx.doi.org/10.1590/S1679-45082013000100024,PMC4872983,23579758,CC BY,"The evaluation of infectious and noninfectious disease management can be done through the use of a time series analysis. In this study, we expect to measure the results and prevent intervention effects on the disease. Clinical studies have benefited from the use of these techniques, particularly for the wide applicability of the ARIMA model. This study briefly presents the process of using the ARIMA model. This analytical tool offers a great contribution for researchers and healthcare managers in the evaluation of healthcare interventions in specific populations.",2013 Jan-Mar,"Sato, Renato Cesar",Einstein (Sao Paulo),,,True
859410b0052a50da3868ab631c6e1a58ff3d4c49,PMC,Toward a Common Secure Future: Four Global Commissions in the Wake of Ebola,http://dx.doi.org/10.1371/journal.pmed.1002042,PMC4873000,27195954,CC BY,Lawrence Gostin and colleagues offer a set of priorities for global health preparedness and response for future infectious disease threats.,2016 May 19,"['Gostin, Lawrence O.', 'Tomori, Oyewale', 'Wibulpolprasert, Suwit', 'Jha, Ashish K.', 'Frenk, Julio', 'Moon, Suerie', 'Phumaphi, Joy', 'Piot, Peter', 'Stocking, Barbara', 'Dzau, Victor J.', 'Leung, Gabriel M.']",PLoS Med,,,True
0a851d4005336287cd41901a8fcd0ba3bab686c9,PMC,Coinfections of the Respiratory Tract: Viral Competition for Resources,http://dx.doi.org/10.1371/journal.pone.0155589,PMC4873262,27196110,CC BY,"Studies have shown that simultaneous infection of the respiratory tract with at least two viruses is common in hospitalized patients, although it is not clear whether these infections are more or less severe than single virus infections. We use a mathematical model to study the dynamics of viral coinfection of the respiratory tract in an effort to understand the kinetics of these infections. Specifically, we use our model to investigate coinfections of influenza, respiratory syncytial virus, rhinovirus, parainfluenza virus, and human metapneumovirus. Our study shows that during coinfections, one virus can block another simply by being the first to infect the available host cells; there is no need for viral interference through immune response interactions. We use the model to calculate the duration of detectable coinfection and examine how it varies as initial viral dose and time of infection are varied. We find that rhinovirus, the fastest-growing virus, reduces replication of the remaining viruses during a coinfection, while parainfluenza virus, the slowest-growing virus is suppressed in the presence of other viruses.",2016 May 19,"['Pinky, Lubna', 'Dobrovolny, Hana M.']",PLoS One,,,True
d56e6ff1dc73a424b1ea4f7f97f1cac72eb67b39,PMC,Coinfections of the Respiratory Tract: Viral Competition for Resources,http://dx.doi.org/10.1371/journal.pone.0155589,PMC4873262,27196110,CC BY,"Studies have shown that simultaneous infection of the respiratory tract with at least two viruses is common in hospitalized patients, although it is not clear whether these infections are more or less severe than single virus infections. We use a mathematical model to study the dynamics of viral coinfection of the respiratory tract in an effort to understand the kinetics of these infections. Specifically, we use our model to investigate coinfections of influenza, respiratory syncytial virus, rhinovirus, parainfluenza virus, and human metapneumovirus. Our study shows that during coinfections, one virus can block another simply by being the first to infect the available host cells; there is no need for viral interference through immune response interactions. We use the model to calculate the duration of detectable coinfection and examine how it varies as initial viral dose and time of infection are varied. We find that rhinovirus, the fastest-growing virus, reduces replication of the remaining viruses during a coinfection, while parainfluenza virus, the slowest-growing virus is suppressed in the presence of other viruses.",2016 May 19,"['Pinky, Lubna', 'Dobrovolny, Hana M.']",PLoS One,,,False
c6f5f979821e78c2d91b1f93a162f3c8542fb64f,PMC,Coinfections of the Respiratory Tract: Viral Competition for Resources,http://dx.doi.org/10.1371/journal.pone.0155589,PMC4873262,27196110,CC BY,"Studies have shown that simultaneous infection of the respiratory tract with at least two viruses is common in hospitalized patients, although it is not clear whether these infections are more or less severe than single virus infections. We use a mathematical model to study the dynamics of viral coinfection of the respiratory tract in an effort to understand the kinetics of these infections. Specifically, we use our model to investigate coinfections of influenza, respiratory syncytial virus, rhinovirus, parainfluenza virus, and human metapneumovirus. Our study shows that during coinfections, one virus can block another simply by being the first to infect the available host cells; there is no need for viral interference through immune response interactions. We use the model to calculate the duration of detectable coinfection and examine how it varies as initial viral dose and time of infection are varied. We find that rhinovirus, the fastest-growing virus, reduces replication of the remaining viruses during a coinfection, while parainfluenza virus, the slowest-growing virus is suppressed in the presence of other viruses.",2016 May 19,"['Pinky, Lubna', 'Dobrovolny, Hana M.']",PLoS One,,,False
40b1e8bb31863fa9488fcbfc590edf4972fe4c0c,PMC,"Glial cell activation, recruitment, and survival of B-lineage cells following MCMV brain infection",http://dx.doi.org/10.1186/s12974-016-0582-y,PMC4874004,27207308,CC BY,"BACKGROUND: Chemokines produced by reactive glia drive migration of immune cells and previous studies from our laboratory have demonstrated that CD19(+) B cells infiltrate the brain. In this study, in vivo and in vitro experiments investigated the role of reactive glial cells in recruitment and survival of B-lineage cells in response to (murine cytomegalovirus) MCMV infection. METHODS: Flow cytometric analysis was used to assess chemokine receptor expression on brain-infiltrating B cells. Real-time RT-PCR and ELISA were used to measure chemokine levels. Dual-immunohistochemical staining was used to co-localize chemokine production by reactive glia. Primary glial cell cultures and migration assays were used to examine chemokine-mediated recruitment. Astrocyte: B cell co-cultures were used to investigate survival and proliferation. RESULTS: The chemokine receptors CXCR3, CXCR5, CCR5, and CCR7 were detected on CD19(+) cells isolated from the brain during MCMV infection. In particular, CXCR3 was found to be elevated on an increasing number of cells over the time course of infection, and it was the primary chemokine receptor expressed at 60 days post infection Quite different expression kinetics were observed for CXCR5, CCR5, and CCR7, which were elevated on the highest number of cells early during infection and decreased by 14, 30, and 60 days post infection Correspondingly, elevated levels of CXCL9, CXCL10, and CXCL13, as well as CCL5, were found within the brains of infected animals, and only low levels of CCL3 and CCL19 were detected. Differential expression of CXCL9/CXCL10 and CXCL13 between microglia and astrocytes was apparent, and B cells moved towards supernatants from MCMV-infected microglia, but not astrocytes. Pretreatment with neutralizing Abs to CXCL9 and CXCL10 inhibited this migration. In contrast, neutralizing Abs to the ligand of CXCR5 (i.e., CXCL13) did not significantly block chemotaxis. Proliferation of brain-infiltrating B cells was detected at 7 days post infection and persisted through the latest time tested (60 days post infection). Finally, astrocytes produce BAFF (B cell activating factor of the TNF family) and promote proliferation of B cells via cell-to-cell contact. CONCLUSIONS: CXCR3 is the primary chemokine receptor on CD19(+) B cells persisting within the brain, and migration to microglial cell supernatants is mediated through this receptor. Correspondingly, microglial cells produce CXCL9 and CXCL10, but not CXCL13. Reactive astrocytes promote B cell proliferation.",2016 May 20,"['Lokensgard, James R.', 'Mutnal, Manohar B.', 'Prasad, Sujata', 'Sheng, Wen', 'Hu, Shuxian']",J Neuroinflammation,,,True
7c8655ffbfd16f13266b635a0a9f907579f0969d,PMC,Resveratrol attenuates cortical neuron activity: roles of large conductance calcium-activated potassium channels and voltage-gated sodium channels,http://dx.doi.org/10.1186/s12929-016-0259-y,PMC4875746,27209372,CC BY,"BACKGROUND: Resveratrol, a phytoalexin found in grapes and red wine, exhibits diverse pharmacological activities. However, relatively little is known about whether resveratrol modulates the ion channels in cortical neurons. The large-conductance calcium-activated potassium channels (BK(Ca)) and voltage-gated sodium channels were expressed in cortical neurons and play important roles in regulation of neuronal excitability. The present study aimed to determine the effects of resveratrol on BK(Ca) currents and voltage-gated sodium currents in cortical neurons. RESULTS: Resveratrol concentration-dependently increased the current amplitude and the opening activity of BK(Ca) channels, but suppressed the amplitude of voltage-gated sodium currents. Similar to the BK(Ca) channel opener NS1619, resveratrol decreased the firing rate of action potentials. In addition, the enhancing effects of BK(Ca) channel blockers tetraethylammonium (TEA) and paxilline on action potential firing were sensitive to resveratrol. Our results indicated that the attenuation of action potential firing rate by resveratrol might be mediated through opening the BK(Ca) channels and closing the voltage-gated sodium channels. CONCLUSIONS: As BK(Ca) channels and sodium channels are critical molecular determinants for seizure generation, our findings suggest that regulation of these two channels in cortical neurons probably makes a considerable contribution to the antiseizure activity of resveratrol.",2016 May 21,"['Wang, Ya-Jean', 'Chan, Ming-Huan', 'Chen, Linyi', 'Wu, Sheng-Nan', 'Chen, Hwei-Hisen']",J Biomed Sci,,,True
2c092e37343c79101dfbf1f9f66a87f569432a29,PMC,Reverse transcription strand invasion based amplification (RT-SIBA): a method for rapid detection of influenza A and B,http://dx.doi.org/10.1007/s00253-016-7491-y,PMC4875950,27063012,CC BY,"Rapid and accurate diagnosis of influenza viruses plays an important role in infection control, as well as in preventing the misuse of antibiotics. Isothermal nucleic acid amplification methods offer significant advantages over the polymerase chain reaction (PCR), since they are more rapid and do not require the sophisticated instruments needed for thermal cycling. We previously described a novel isothermal nucleic acid amplification method, ‘Strand Invasion Based Amplification’ (SIBA®), with high analytical sensitivity and specificity, for the detection of DNA. In this study, we describe the development of a variant of the SIBA method, namely, reverse transcription SIBA (RT-SIBA), for the rapid detection of viral RNA targets. The RT-SIBA method includes a reverse transcriptase enzyme that allows one-step reverse transcription of RNA to complementary DNA (cDNA) and simultaneous amplification and detection of the cDNA by SIBA under isothermal reaction conditions. The RT-SIBA method was found to be more sensitive than PCR for the detection of influenza A and B and could detect 100 copies of influenza RNA within 15 min. The development of RT-SIBA will enable rapid and accurate diagnosis of viral RNA targets within point-of-care or central laboratory settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-016-7491-y) contains supplementary material, which is available to authorized users.",2016 Apr 11,"['Eboigbodin, Kevin', 'Filén, Sanna', 'Ojalehto, Tuomas', 'Brummer, Mirko', 'Elf, Sonja', 'Pousi, Kirsi', 'Hoser, Mark']",Appl Microbiol Biotechnol,,,False
4ef86c928be12807b78ebc327eb41f0380cf0b75,PMC,Reverse transcription strand invasion based amplification (RT-SIBA): a method for rapid detection of influenza A and B,http://dx.doi.org/10.1007/s00253-016-7491-y,PMC4875950,27063012,CC BY,"Rapid and accurate diagnosis of influenza viruses plays an important role in infection control, as well as in preventing the misuse of antibiotics. Isothermal nucleic acid amplification methods offer significant advantages over the polymerase chain reaction (PCR), since they are more rapid and do not require the sophisticated instruments needed for thermal cycling. We previously described a novel isothermal nucleic acid amplification method, ‘Strand Invasion Based Amplification’ (SIBA®), with high analytical sensitivity and specificity, for the detection of DNA. In this study, we describe the development of a variant of the SIBA method, namely, reverse transcription SIBA (RT-SIBA), for the rapid detection of viral RNA targets. The RT-SIBA method includes a reverse transcriptase enzyme that allows one-step reverse transcription of RNA to complementary DNA (cDNA) and simultaneous amplification and detection of the cDNA by SIBA under isothermal reaction conditions. The RT-SIBA method was found to be more sensitive than PCR for the detection of influenza A and B and could detect 100 copies of influenza RNA within 15 min. The development of RT-SIBA will enable rapid and accurate diagnosis of viral RNA targets within point-of-care or central laboratory settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-016-7491-y) contains supplementary material, which is available to authorized users.",2016 Apr 11,"['Eboigbodin, Kevin', 'Filén, Sanna', 'Ojalehto, Tuomas', 'Brummer, Mirko', 'Elf, Sonja', 'Pousi, Kirsi', 'Hoser, Mark']",Appl Microbiol Biotechnol,,,True
8303edd7c319344d34223d60c9578385684a7f28,PMC,Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene,http://dx.doi.org/10.1038/srep26311,PMC4876326,27212633,CC BY,"Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.",2016 May 23,"['Schobel, Seth A.', 'Stucker, Karla M.', 'Moore, Martin L.', 'Anderson, Larry J.', 'Larkin, Emma K.', 'Shankar, Jyoti', 'Bera, Jayati', 'Puri, Vinita', 'Shilts, Meghan H.', 'Rosas-Salazar, Christian', 'Halpin, Rebecca A.', 'Fedorova, Nadia', 'Shrivastava, Susmita', 'Stockwell, Timothy B.', 'Peebles, R. Stokes', 'Hartert, Tina V.', 'Das, Suman R.']",Sci Rep,,,True
8ccc3179663909f2288db1287ef94906fb03d3b7,PMC,Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene,http://dx.doi.org/10.1038/srep26311,PMC4876326,27212633,CC BY,"Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.",2016 May 23,"['Schobel, Seth A.', 'Stucker, Karla M.', 'Moore, Martin L.', 'Anderson, Larry J.', 'Larkin, Emma K.', 'Shankar, Jyoti', 'Bera, Jayati', 'Puri, Vinita', 'Shilts, Meghan H.', 'Rosas-Salazar, Christian', 'Halpin, Rebecca A.', 'Fedorova, Nadia', 'Shrivastava, Susmita', 'Stockwell, Timothy B.', 'Peebles, R. Stokes', 'Hartert, Tina V.', 'Das, Suman R.']",Sci Rep,,,False
88e54a41da94777eb018ae7915e92f5ad28cf706,PMC,Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene,http://dx.doi.org/10.1038/srep26311,PMC4876326,27212633,CC BY,"Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.",2016 May 23,"['Schobel, Seth A.', 'Stucker, Karla M.', 'Moore, Martin L.', 'Anderson, Larry J.', 'Larkin, Emma K.', 'Shankar, Jyoti', 'Bera, Jayati', 'Puri, Vinita', 'Shilts, Meghan H.', 'Rosas-Salazar, Christian', 'Halpin, Rebecca A.', 'Fedorova, Nadia', 'Shrivastava, Susmita', 'Stockwell, Timothy B.', 'Peebles, R. Stokes', 'Hartert, Tina V.', 'Das, Suman R.']",Sci Rep,,,False
de7726a88ffb639c59dcdec8eb0f76501c56c96c,PMC,Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene,http://dx.doi.org/10.1038/srep26311,PMC4876326,27212633,CC BY,"Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.",2016 May 23,"['Schobel, Seth A.', 'Stucker, Karla M.', 'Moore, Martin L.', 'Anderson, Larry J.', 'Larkin, Emma K.', 'Shankar, Jyoti', 'Bera, Jayati', 'Puri, Vinita', 'Shilts, Meghan H.', 'Rosas-Salazar, Christian', 'Halpin, Rebecca A.', 'Fedorova, Nadia', 'Shrivastava, Susmita', 'Stockwell, Timothy B.', 'Peebles, R. Stokes', 'Hartert, Tina V.', 'Das, Suman R.']",Sci Rep,,,False
bf3e0264c05ee78d66269189d8ed448bc13d4b62,PMC,Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene,http://dx.doi.org/10.1038/srep26311,PMC4876326,27212633,CC BY,"Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.",2016 May 23,"['Schobel, Seth A.', 'Stucker, Karla M.', 'Moore, Martin L.', 'Anderson, Larry J.', 'Larkin, Emma K.', 'Shankar, Jyoti', 'Bera, Jayati', 'Puri, Vinita', 'Shilts, Meghan H.', 'Rosas-Salazar, Christian', 'Halpin, Rebecca A.', 'Fedorova, Nadia', 'Shrivastava, Susmita', 'Stockwell, Timothy B.', 'Peebles, R. Stokes', 'Hartert, Tina V.', 'Das, Suman R.']",Sci Rep,,,False
bdd2c70f5e1dd38c3983adeac033665b7ac56909,PMC,Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene,http://dx.doi.org/10.1038/srep26311,PMC4876326,27212633,CC BY,"Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.",2016 May 23,"['Schobel, Seth A.', 'Stucker, Karla M.', 'Moore, Martin L.', 'Anderson, Larry J.', 'Larkin, Emma K.', 'Shankar, Jyoti', 'Bera, Jayati', 'Puri, Vinita', 'Shilts, Meghan H.', 'Rosas-Salazar, Christian', 'Halpin, Rebecca A.', 'Fedorova, Nadia', 'Shrivastava, Susmita', 'Stockwell, Timothy B.', 'Peebles, R. Stokes', 'Hartert, Tina V.', 'Das, Suman R.']",Sci Rep,,,False
151fe22ecfaef4184f29724d622cce8012ee0b50,PMC,Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene,http://dx.doi.org/10.1038/srep26311,PMC4876326,27212633,CC BY,"Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.",2016 May 23,"['Schobel, Seth A.', 'Stucker, Karla M.', 'Moore, Martin L.', 'Anderson, Larry J.', 'Larkin, Emma K.', 'Shankar, Jyoti', 'Bera, Jayati', 'Puri, Vinita', 'Shilts, Meghan H.', 'Rosas-Salazar, Christian', 'Halpin, Rebecca A.', 'Fedorova, Nadia', 'Shrivastava, Susmita', 'Stockwell, Timothy B.', 'Peebles, R. Stokes', 'Hartert, Tina V.', 'Das, Suman R.']",Sci Rep,,,False
eaa5563d3b1791ebb166e18abfaba4e22b965049,PMC,The scanning electron microscope in microbiology and diagnosis of infectious disease,http://dx.doi.org/10.1038/srep26516,PMC4876401,27212232,CC BY,"Despite being an excellent tool for investigating ultrastructure, scanning electron microscopy (SEM) is less frequently used than transmission electron microscopy for microbes such as viruses or bacteria. Here we describe rapid methods that allow SEM imaging of fully hydrated, unfixed microbes without using conventional sample preparation methods. We demonstrate improved ultrastructural preservation, with greatly reduced dehydration and shrinkage, for specimens including bacteria and viruses such as Ebola virus using infiltration with ionic liquid on conducting filter substrates for SEM.",2016 May 23,"['Golding, Christine G.', 'Lamboo, Lindsey L.', 'Beniac, Daniel R.', 'Booth, Timothy F.']",Sci Rep,,,True
8766e2b5d1ae6c890710a3c8bccd1321d15db79f,PMC,The scanning electron microscope in microbiology and diagnosis of infectious disease,http://dx.doi.org/10.1038/srep26516,PMC4876401,27212232,CC BY,"Despite being an excellent tool for investigating ultrastructure, scanning electron microscopy (SEM) is less frequently used than transmission electron microscopy for microbes such as viruses or bacteria. Here we describe rapid methods that allow SEM imaging of fully hydrated, unfixed microbes without using conventional sample preparation methods. We demonstrate improved ultrastructural preservation, with greatly reduced dehydration and shrinkage, for specimens including bacteria and viruses such as Ebola virus using infiltration with ionic liquid on conducting filter substrates for SEM.",2016 May 23,"['Golding, Christine G.', 'Lamboo, Lindsey L.', 'Beniac, Daniel R.', 'Booth, Timothy F.']",Sci Rep,,,False
698174035746c185ce55489b4a345026d82dcc42,PMC,Transcriptional Analysis of PRRSV-Infected Porcine Dendritic Cell Response to Streptococcus suis Infection Reveals Up-Regulation of Inflammatory-Related Genes Expression,http://dx.doi.org/10.1371/journal.pone.0156019,PMC4877111,27213692,CC BY,"The porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important swine pathogens and often serves as an entry door for other viral or bacterial pathogens, of which Streptococcus suis is one of the most common. Pre-infection with PRRSV leads to exacerbated disease caused by S. suis infection. Very few studies have assessed the immunological mechanisms underlying this higher susceptibility. Since antigen presenting cells play a major role in the initiation of the immune response, the in vitro transcriptional response of bone marrow-derived dendritic cells (BMDCs) and monocytes in the context of PRRSV and S. suis co-infection was investigated. BMDCs were found to be more permissive than monocytes to PRRSV infection; S. suis phagocytosis by PRRSV-infected BMDCs was found to be impaired, whereas no effect was found on bacterial intracellular survival. Transcription profile analysis, with a major focus on inflammatory genes, following S. suis infection, with and without pre-infection with PRRSV, was then performed. While PRRSV pre-infection had little effect on monocytes response to S. suis infection, a significant expression of several pro-inflammatory molecules was observed in BMDCs pre-infected with PRRSV after a subsequent infection with S. suis. While an additive effect could be observed for CCL4, CCL14, CCL20, and IL-15, a distinct synergistic up-regulatory effect was observed for IL-6, CCL5 and TNF-α after co-infection. This increased pro-inflammatory response by DCs could participate in the exacerbation of the disease observed during PRRSV and S. suis co-infection.",2016 May 23,"['Auray, Gaël', 'Lachance, Claude', 'Wang, Yingchao', 'Gagnon, Carl A.', 'Segura, Mariela', 'Gottschalk, Marcelo']",PLoS One,,,True
59d3f98d78f2ff993174b173807435e75df8bc3a,PMC,Evidence for widespread infection of African bats with Crimean-Congo hemorrhagic fever-like viruses,http://dx.doi.org/10.1038/srep26637,PMC4877572,27217069,CC BY,"Crimean Congo hemorrhagic fever virus (CCHFV) is a highly virulent tick-borne pathogen that causes hemorrhagic fever in humans. The geographic range of human CCHF cases largely reflects the presence of ticks. However, highly similar CCHFV lineages occur in geographically distant regions. Tick-infested migratory birds have been suggested, but not confirmed, to contribute to the dispersal. Bats have recently been shown to carry nairoviruses distinct from CCHFV. In order to assess the presence of CCHFV in a wide range of bat species over a wide geographic range, we analyzed 1,135 sera from 16 different bat species collected in Congo, Gabon, Ghana, Germany, and Panama. Using a CCHFV glycoprotein-based indirect immunofluorescence test (IIFT), we identified reactive antibodies in 10.0% (114/1,135) of tested bats, pertaining to 12/16 tested species. Depending on the species, 3.6%–42.9% of cave-dwelling bats and 0.6%–7.1% of foliage-living bats were seropositive (two-tailed t-test, p = 0.0447 cave versus foliage). 11/30 IIFT-reactive sera from 10 different African bat species had neutralizing activity in a virus-like particle assay. Neutralization of full CCHFV was confirmed in 5 of 7 sera. Widespread infection of cave-dwelling bats may indicate a role for bats in the life cycle and geographic dispersal of CCHFV.",2016 May 24,"['Müller, Marcel A.', 'Devignot, Stéphanie', 'Lattwein, Erik', 'Corman, Victor Max', 'Maganga, Gaël D.', 'Gloza-Rausch, Florian', 'Binger, Tabea', 'Vallo, Peter', 'Emmerich, Petra', 'Cottontail, Veronika M.', 'Tschapka, Marco', 'Oppong, Samuel', 'Drexler, Jan Felix', 'Weber, Friedemann', 'Leroy, Eric M.', 'Drosten, Christian']",Sci Rep,,,True
62406757c331d6c939bf09fa005bb565b3fac0b9,PMC,Lack of transmission among healthcare workers in contact with a case of Middle East respiratory syndrome coronavirus infection in Thailand,http://dx.doi.org/10.1186/s13756-016-0120-9,PMC4877934,27222710,CC BY,"INTRODUCTION: A hospital-associated outbreak of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was reported. We aimed to assess the effectiveness of infection control measures among healthcare workers (HCWs) who were exposed to a MERS patient and/or his body fluids in our institute. METHODS: A descriptive study was conducted among HCWs who worked with a MERS patient in Bamrasnaradura Infectious Diseases Institute, Thailand, between 18 June and 3 July 2015. Contacts were defined as HCWs who worked in the patient’s room or with the patient’s body fluids. Serum samples from all contacts were collected within 14 days of last contact and one month later. Paired sera were tested for detection of MERS‐CoV antibodies by using an indirect ELISA. RESULTS: Thirty-eight (88.4 %) of 43 identified contacts consented to enroll. The mean (SD) age was 38.1 (11.1) years, and 79 % were females. The median (IQR) cumulative duration of work of HCWs in the patient’s room was 35 (20–165) minutes. The median (IQR) cumulative duration of work of HCWs with the patient’s blood or body fluids in laboratory was 67.5 (43.7–117.5) minutes. All contacts reported 100 % compliance with hand hygiene, using N95 respirator, performing respirator fit test, wearing gown, gloves, eye protection, and cap during their entire working period. All serum specimens of contacts tested for MERS-CoV antibodies were negative. CONCLUSIONS: We provide evidence of effective infection control practices against MERS-CoV transmission in a healthcare facility. Strict infection control precautions can protect HCWs. The optimal infection control measures for MERS-CoV should be further evaluated.",2016 May 23,"['Wiboonchutikul, Surasak', 'Manosuthi, Weerawat', 'Likanonsakul, Sirirat', 'Sangsajja, Chariya', 'Kongsanan, Paweena', 'Nitiyanontakij, Ravee', 'Thientong, Varaporn', 'Lerdsamran, Hatairat', 'Puthavathana, Pilaipan']",Antimicrob Resist Infect Control,,,True
63cfe8fa64e33300471ac1e2a5b87cb52be553d9,PMC,A de novo transcriptome analysis shows that modulation of the JAK-STAT signaling pathway by salmonid alphavirus subtype 3 favors virus replication in macrophage/dendritic-like TO-cells,http://dx.doi.org/10.1186/s12864-016-2739-6,PMC4878077,27215196,CC BY,"BACKGROUND: The Janus kinase (Jak) and signaling transducer activator of transcription (Stat) pathway mediates the signaling of genes required for cellular development and homeostasis. To elucidate the effect of type I IFN on the Jak/stat pathway in salmonid alphavirus subtype 3 (SAV3) infected macrophage/dendritic like TO-cells derived from Atlantic salmon (Salmo salar L) headkidney leukocytes, we used a differential transcriptome analysis by RNA-seq and the Kyoto encyclopedia of genes and genomes (KEGGs) pathway analysis to generate a repertoire of de novo assembled genes from type I IFN treated and non-treated TO-cells infected with SAV3. RESULTS: Concurrent SAV3 infection with type I IFN treatment of TO-cells suppressed SAV3 structural protein (SP) expression by 2log(10) at 2 days post infection compared to SAV3 infection without IFN treatment which paved way to evaluating the impact of type I IFN on expression of Jak/stat pathway genes in SAV3 infected TO-cells. In the absence of type I IFN treatment, SAV3 downregulated several Jak/stat pathway genes that included type I and II receptor genes, Jak2, tyrosine kinase 2 (Tyk2), Stat3 and Stat5 pointing to possible failure to activate the Jak/stat signaling pathway and inhibition of signal transducers caused by SAV3 infection. Although the suppressor of cytokine signaling (SOCS) genes 1 and 3 were upregulated in the IFN treated cells, only SOCS3 was downregulated in the SAV3 infected cells which points to inhibition of SOCS3 by SAV3 infection in TO-cells. CONCLUSION: Data presented in this study shows that SAV3 infection downregulates several genes of the Jak/stat pathway, which could be an immune evasion strategy, used to block the transcription of antiviral genes that would interfere with SAV3 replication in TO-cells. Overall, we have shown that combining de novo assembly with pathway based transcriptome analyses provides a contextual approach to understanding the molecular networks of genes that form the Jak/stat pathway in TO-cells infected by SAV3.",2016 May 23,"['Xu, Cheng', 'Evensen, Øystein', 'Munang’andu, Hetron Mweemba']",BMC Genomics,,,True
c2749a18c00e1668167a5f65d6d9ff7896f25465,PMC,Respiratory syncytial virus seasonality in Brazil: implications for the immunisation policy for at-risk populations,http://dx.doi.org/10.1590/0074-02760150341,PMC4878298,27120006,CC BY,"Respiratory syncytial virus (RSV) infection is the leading cause of hospitalisation for respiratory diseases among children under 5 years old. The aim of this study was to analyse RSV seasonality in the five distinct regions of Brazil using time series analysis (wavelet and Fourier series) of the following indicators: monthly positivity of the immunofluorescence reaction for RSV identified by virologic surveillance system, and rate of hospitalisations per bronchiolitis and pneumonia due to RSV in children under 5 years old (codes CID-10 J12.1, J20.5, J21.0 and J21.9). A total of 12,501 samples with 11.6% positivity for RSV (95% confidence interval 11 - 12.2), varying between 7.1 and 21.4% in the five Brazilian regions, was analysed. A strong trend for annual cycles with a stable stationary pattern in the five regions was identified through wavelet analysis of the indicators. The timing of RSV activity by Fourier analysis was similar between the two indicators analysed and showed regional differences. This study reinforces the importance of adjusting the immunisation period for high risk population with the monoclonal antibody palivizumab taking into account regional differences in seasonality of RSV.",2016 May,"['Freitas, André Ricardo Ribas', 'Donalisio, Maria Rita']",Mem Inst Oswaldo Cruz,,,True
8b221945f093d8d13835556a56c2a1d8f02e2705,PMC,Innate Immune Responses in ALV-J Infected Chicks and Chickens with Hemangioma In Vivo,http://dx.doi.org/10.3389/fmicb.2016.00786,PMC4879323,27252695,CC BY,"Avian leukosis virus subgroup J (ALV-J) infection can cause tumors and immunosuppression. Since the precise mechanism of the innate immune response induced by ALV-J is unknown, we investigated the antiviral innate immune responses induced by ALV-J in chicks and chickens that had developed tumors. Spleen levels of interleukin-6 (IL-6), IL-10, IL-1β, and interferon-β (IFN-β) were not significantly different between the infected chick groups and the control groups from 1 day post hatch to 7 days post hatch. However, IL-6, IL-1β, and IFN-β protein levels in the three clinical samples with hemangiomas were dramatically increased compared to the healthy samples. In addition, the anti-inflammatory cytokine IL-10 increased sharply in two of three clinical samples. We also found a more than 20-fold up-regulation of ISG12-1 mRNA at 1 day post infection (d.p.i.) and a twofold up-regulation of ZC3HAV1 mRNA at 4 d.p.i. However, there were no statistical differences in ISG12-1 and ZC3HAV1 mRNA expression levels in the tumorigenesis phase. ALV-J infection induced a significant increase of Toll-like receptor 7 (TLR-7) at 1 d.p.i. and dramatically increased the mRNA levels of melanoma differentiation-associated gene 5 (MDA5) in the tumorigenesis phase. Moreover, the protein levels of interferon regulatory factor 1 (IRF-1) and signal transducer and activator of transcription 1 (STAT1) were decreased in chickens with tumors. These results suggest that ALV-J was primarily recognized by chicken TLR7 and MDA5 at early and late in vivo infection stages, respectively. ALV-J strain SCAU-HN06 did not induce any significant antiviral innate immune response in 1 week old chicks. However, interferon-stimulated genes were not induced normally during the late phase of ALV-J infection due to a reduction of IRF1 and STAT1 expression.",2016 May 25,"['Feng, Min', 'Dai, Manman', 'Xie, Tingting', 'Li, Zhenhui', 'Shi, Meiqing', 'Zhang, Xiquan']",Front Microbiol,,,True
6518eb44df3244c513ccb0ceea5b7f3eb3dd9b52,PMC,Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing,http://dx.doi.org/10.1038/srep26017,PMC4879520,27221218,CC BY,"Emerging and re-emerging infectious diseases caused by RNA viruses pose a critical public health threat. Next generation sequencing (NGS) is a powerful technology to define genomic sequences of the viruses. Of particular interest is the use of whole genome sequencing (WGS) to perform phylogeographic analysis, that allows the detection and tracking of the emergence of viral infections. Hantaviruses, Bunyaviridae, cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans. We propose to use WGS for the phylogeographic analysis of human hantavirus infections. A novel multiplex PCR-based NGS was developed to gather whole genome sequences of Hantaan virus (HTNV) from HFRS patients and rodent hosts in endemic areas. The obtained genomes were described for the spatial and temporal links between cases and their sources. Phylogenetic analyses demonstrated geographic clustering of HTNV strains from clinical specimens with the HTNV strains circulating in rodents, suggesting the most likely site and time of infection. Recombination analysis demonstrated a genome organization compatible with recombination of the HTNV S segment. The multiplex PCR-based NGS is useful and robust to acquire viral genomic sequences and may provide important ways to define the phylogeographical association and molecular evolution of hantaviruses.",2016 May 25,"['Kim, Won-Keun', 'Kim, Jeong-Ah', 'Song, Dong Hyun', 'Lee, Daesang', 'Kim, Yong Chul', 'Lee, Sook-Young', 'Lee, Seung-Ho', 'No, Jin Sun', 'Kim, Ji Hye', 'Kho, Jeong Hoon', 'Gu, Se Hun', 'Jeong, Seong Tae', 'Wiley, Michael', 'Kim, Heung-Chul', 'Klein, Terry A.', 'Palacios, Gustavo', 'Song, Jin-Won']",Sci Rep,,,True
27052d6e2693fe9dfae4a746408e16180ed57243,PMC,Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing,http://dx.doi.org/10.1038/srep26017,PMC4879520,27221218,CC BY,"Emerging and re-emerging infectious diseases caused by RNA viruses pose a critical public health threat. Next generation sequencing (NGS) is a powerful technology to define genomic sequences of the viruses. Of particular interest is the use of whole genome sequencing (WGS) to perform phylogeographic analysis, that allows the detection and tracking of the emergence of viral infections. Hantaviruses, Bunyaviridae, cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans. We propose to use WGS for the phylogeographic analysis of human hantavirus infections. A novel multiplex PCR-based NGS was developed to gather whole genome sequences of Hantaan virus (HTNV) from HFRS patients and rodent hosts in endemic areas. The obtained genomes were described for the spatial and temporal links between cases and their sources. Phylogenetic analyses demonstrated geographic clustering of HTNV strains from clinical specimens with the HTNV strains circulating in rodents, suggesting the most likely site and time of infection. Recombination analysis demonstrated a genome organization compatible with recombination of the HTNV S segment. The multiplex PCR-based NGS is useful and robust to acquire viral genomic sequences and may provide important ways to define the phylogeographical association and molecular evolution of hantaviruses.",2016 May 25,"['Kim, Won-Keun', 'Kim, Jeong-Ah', 'Song, Dong Hyun', 'Lee, Daesang', 'Kim, Yong Chul', 'Lee, Sook-Young', 'Lee, Seung-Ho', 'No, Jin Sun', 'Kim, Ji Hye', 'Kho, Jeong Hoon', 'Gu, Se Hun', 'Jeong, Seong Tae', 'Wiley, Michael', 'Kim, Heung-Chul', 'Klein, Terry A.', 'Palacios, Gustavo', 'Song, Jin-Won']",Sci Rep,,,False
b971e1834336cb9157841f3e501b68a7031ff518,PMC,Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing,http://dx.doi.org/10.1038/srep26017,PMC4879520,27221218,CC BY,"Emerging and re-emerging infectious diseases caused by RNA viruses pose a critical public health threat. Next generation sequencing (NGS) is a powerful technology to define genomic sequences of the viruses. Of particular interest is the use of whole genome sequencing (WGS) to perform phylogeographic analysis, that allows the detection and tracking of the emergence of viral infections. Hantaviruses, Bunyaviridae, cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans. We propose to use WGS for the phylogeographic analysis of human hantavirus infections. A novel multiplex PCR-based NGS was developed to gather whole genome sequences of Hantaan virus (HTNV) from HFRS patients and rodent hosts in endemic areas. The obtained genomes were described for the spatial and temporal links between cases and their sources. Phylogenetic analyses demonstrated geographic clustering of HTNV strains from clinical specimens with the HTNV strains circulating in rodents, suggesting the most likely site and time of infection. Recombination analysis demonstrated a genome organization compatible with recombination of the HTNV S segment. The multiplex PCR-based NGS is useful and robust to acquire viral genomic sequences and may provide important ways to define the phylogeographical association and molecular evolution of hantaviruses.",2016 May 25,"['Kim, Won-Keun', 'Kim, Jeong-Ah', 'Song, Dong Hyun', 'Lee, Daesang', 'Kim, Yong Chul', 'Lee, Sook-Young', 'Lee, Seung-Ho', 'No, Jin Sun', 'Kim, Ji Hye', 'Kho, Jeong Hoon', 'Gu, Se Hun', 'Jeong, Seong Tae', 'Wiley, Michael', 'Kim, Heung-Chul', 'Klein, Terry A.', 'Palacios, Gustavo', 'Song, Jin-Won']",Sci Rep,,,False
46db8b3db38acf771fe27031fee9445b99146308,PMC,Epigenetic Effect of Environmental Factors on Autism Spectrum Disorders,http://dx.doi.org/10.3390/ijerph13050504,PMC4881129,27187441,CC BY,"Both environmental factors and genetic factors are involved in the pathogenesis of autism spectrum disorders (ASDs). Epigenetics, an essential mechanism for gene regulation based on chemical modifications of DNA and histone proteins, is also involved in congenital ASDs. It was recently demonstrated that environmental factors, such as endocrine disrupting chemicals and mental stress in early life, can change epigenetic status and gene expression, and can cause ASDs. Moreover, environmentally induced epigenetic changes are not erased during gametogenesis and are transmitted to subsequent generations, leading to changes in behavior phenotypes. However, epigenetics has a reversible nature since it is based on the addition or removal of chemical residues, and thus the original epigenetic status may be restored. Indeed, several antidepressants and anticonvulsants used for mental disorders including ASDs restore the epigenetic state and gene expression. Therefore, further epigenetic understanding of ASDs is important for the development of new drugs that take advantages of epigenetic reversibility.",2016 May 14,"['Kubota, Takeo', 'Mochizuki, Kazuki']",Int J Environ Res Public Health,,,True
588631c5434bdc11922450678d5d65823f62e432,PMC,A Brief Review of Computer-Assisted Approaches to Rational Design of Peptide Vaccines,http://dx.doi.org/10.3390/ijms17050666,PMC4881492,27153063,CC BY,"The growing incidences of new viral diseases and increasingly frequent viral epidemics have strained therapeutic and preventive measures; the high mutability of viral genes puts additional strains on developmental efforts. Given the high cost and time requirements for new drugs development, vaccines remain as a viable alternative, but there too traditional techniques of live-attenuated or inactivated vaccines have the danger of allergenic reactions and others. Peptide vaccines have, over the last several years, begun to be looked on as more appropriate alternatives, which are economically affordable, require less time for development and hold the promise of multi-valent dosages. The developments in bioinformatics, proteomics, immunogenomics, structural biology and other sciences have spurred the growth of vaccinomics where computer assisted approaches serve to identify suitable peptide targets for eventual development of vaccines. In this mini-review we give a brief overview of some of the recent trends in computer assisted vaccine development with emphasis on the primary selection procedures of probable peptide candidates for vaccine development.",2016 May 4,"['Nandy, Ashesh', 'Basak, Subhash C.']",Int J Mol Sci,,,True
d117c8256785f2ff80a40fba878aa4f022d8310b,PMC,SARS Coronavirus Papain-Like Protease Inhibits the TLR7 Signaling Pathway through Removing Lys63-Linked Polyubiquitination of TRAF3 and TRAF6,http://dx.doi.org/10.3390/ijms17050678,PMC4881504,27164085,CC BY,"Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLPro) reportedly inhibits the production of type I interferons (IFNs) and pro-inflammatory cytokines in Toll-like receptor 3 (TLR3) and retinoic acid-inducible gene 1 (RIG-I) pathways. The study investigated the inhibitory effect and its antagonistic mechanism of SARS-CoV PLPro on TLR7-mediated cytokine production. TLR7 agonist (imiquimod (IMQ)) concentration-dependently induced activation of ISRE-, NF-κB- and AP-1-luciferase reporters, as well as the production of IFN-α, IFN-β, TNF-α, IL-6 and IL-8 in human promonocyte cells. However, SARS-CoV PLPro significantly inhibited IMQ-induced cytokine production through suppressing the activation of transcription factors IRF-3, NF-κB and AP-1. Western blot analysis with anti-Lys48 and anti-Lys63 ubiquitin antibodies indicated the SARS-CoV PLPro removed Lys63-linked ubiquitin chains of TRAF3 and TRAF6, but not Lys48-linked ubiquitin chains in un-treated and treated cells. The decrease in the activated state of TRAF3 and TRAF6 correlated with the inactivation of TBK1 in response to IMQ by PLPro. The results revealed that the antagonism of SARS-CoV PLPro on TLR7-mediated innate immunity was associated with the negative regulation of TRAF3/6-TBK1-IRF3/NF-κB/AP1 signals.",2016 May 5,"['Li, Shih-Wen', 'Wang, Ching-Ying', 'Jou, Yu-Jen', 'Huang, Su-Hua', 'Hsiao, Li-Hsin', 'Wan, Lei', 'Lin, Ying-Ju', 'Kung, Szu-Hao', 'Lin, Cheng-Wen']",Int J Mol Sci,,,True
13e902f62fb20b66fbbc69e9ec434243342d16cd,PMC,Isolation and Characterization of Dromedary Camel Coronavirus UAE-HKU23 from Dromedaries of the Middle East: Minimal Serological Cross-Reactivity between MERS Coronavirus and Dromedary Camel Coronavirus UAE-HKU23,http://dx.doi.org/10.3390/ijms17050691,PMC4881517,27164099,CC BY,"Recently, we reported the discovery of a dromedary camel coronavirus UAE-HKU23 (DcCoV UAE-HKU23) from dromedaries in the Middle East. In this study, DcCoV UAE-HKU23 was successfully isolated in two of the 14 dromedary fecal samples using HRT-18G cells, with cytopathic effects observed five days after inoculation. Northern blot analysis revealed at least seven distinct RNA species, corresponding to predicted subgenomic mRNAs and confirming the core sequence of transcription regulatory sequence motifs as 5′-UCUAAAC-3′ as we predicted previously. Antibodies against DcCoV UAE-HKU23 were detected in 58 (98.3%) and 59 (100%) of the 59 dromedary sera by immunofluorescence and neutralization antibody tests, respectively. There was significant correlation between the antibody titers determined by immunofluorescence and neutralization assays (Pearson coefficient = 0.525, p < 0.0001). Immunization of mice using recombinant N proteins of DcCoV UAE-HKU23 and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively, and heat-inactivated DcCoV UAE-HKU23 showed minimal cross-antigenicity between DcCoV UAE-HKU23 and MERS-CoV by Western blot and neutralization antibody assays. Codon usage and genetic distance analysis of RdRp, S and N genes showed that the 14 strains of DcCoV UAE-HKU23 formed a distinct cluster, separated from those of other closely related members of Betacoronavirus 1, including alpaca CoV, confirming that DcCoV UAE-HKU23 is a novel member of Betacoronavirus 1.",2016 May 7,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Fan, Rachel Y. Y.', 'Lau, Candy C. Y.', 'Wong, Emily Y. M.', 'Joseph, Sunitha', 'Tsang, Alan K. L.', 'Wernery, Renate', 'Yip, Cyril C. Y.', 'Tsang, Chi-Ching', 'Wernery, Ulrich', 'Yuen, Kwok-Yung']",Int J Mol Sci,,,True
92f465e2f870b70dfea013a01bc9ccfa46c511de,PMC,Pigment Epithelium-Derived Factor (PEDF) Protects Osteoblastic Cell Line from Glucocorticoid-Induced Apoptosis via PEDF-R,http://dx.doi.org/10.3390/ijms17050730,PMC4881552,27187377,CC BY,"Pigment epithelial-derived factor (PEDF) is known as a widely expressed multifunctional secreted glycoprotein whose biological actions are cell-type dependent. Recent studies demonstrated that PEDF displays cytoprotective activity in several cell types. However, it remains unknown whether PEDF is involved in glucocorticoid-induced osteoblast death. The aim of this study was to examine the role of PEDF in osteoblast survival in response to dexamethasone, an active glucocorticoid analogue, and explore the underlying mechanism. In the present study, dexamethasone (DEX) was used to induce MC3T3-E1 pre-osteoblast apoptosis. PEDF mRNA and protein levels and cell apoptosis were determined respectively. Then PEDF receptor (PEDF-R)- and lysophosphatidic acid (LPA)-related signal transductions were assessed. Here we show that DEX down-regulates PEDF expression, which contributes to osteoblast apoptosis. As a result, exogenous recombinant PEDF (rPEDF) inhibited DEX-induced cell apoptosis. We confirmed that PEDF-R was expressed on MC3T3-E1 pre-osteoblast membrane and could bind to PEDF which increased the level of LPA and activated the phosphorylation of Akt. Our results suggest that PEDF attenuated DEX-induced apoptosis in MC3T3-E1 pre-osteoblasts through LPA-dependent Akt activation via PEDF-R.",2016 May 13,"['Yao, Shengcheng', 'Zhang, Yingnan', 'Wang, Xiaoyu', 'Zhao, Fengchao', 'Sun, Maji', 'Zheng, Xin', 'Dong, Hongyan', 'Guo, Kaijin']",Int J Mol Sci,,,True
7c0168a4b858a8680f305fc4d8cc3c787ff4e110,PMC,Efficient suilysin-mediated invasion and apoptosis in porcine respiratory epithelial cells after streptococcal infection under air-liquid interface conditions,http://dx.doi.org/10.1038/srep26748,PMC4882623,27229328,CC BY,"Streptococci may colonize the epithelium in the airways and other entry sites. While local infection often remains asymptomatic, severe or even fatal diseases occur when streptococci become invasive and spread to different sites in the infected host. We have established porcine respiratory air-liquid interface cultures (ALI) from the porcine lung to analyze the interaction of streptococci with their primary target cells. As representative of the streptococcal family we chose Streptococcus suis (S. suis) that is not only a major swine respiratory pathogen but can also infect humans. Suilysin, a cholesterol-dependent cytolysin (CDC), is an important virulence factor. By comparing a S. suis wt strain with a suilysin-deficient mutant, we demonstrate that suilysin contributes to (i) adherence to airway cells (ii) loss of ciliated cells (iii) apoptosis, and (iv) invasion. Furthermore, we show that cytolytic activity of suilysin is crucial for these effects. A striking result of our analysis was the high efficiency of S. suis-induced apoptosis and invasion upon infection under ALI conditions. These properties have been reported to be less efficient when analyzed with immortalized cells. We hypothesize that soluble effectors such as suilysin are present at higher concentrations in cells kept at ALI conditions and thus more effective. These results should be relevant also for infection of the respiratory tract by other respiratory pathogens.",2016 May 27,"['Meng, Fandan', 'Wu, Nai-Huei', 'Seitz, Maren', 'Herrler, Georg', 'Valentin-Weigand, Peter']",Sci Rep,,,True
b67e67fb94c0a813f6ca3b19aabc69ee7070f8d4,PMC,Efficient suilysin-mediated invasion and apoptosis in porcine respiratory epithelial cells after streptococcal infection under air-liquid interface conditions,http://dx.doi.org/10.1038/srep26748,PMC4882623,27229328,CC BY,"Streptococci may colonize the epithelium in the airways and other entry sites. While local infection often remains asymptomatic, severe or even fatal diseases occur when streptococci become invasive and spread to different sites in the infected host. We have established porcine respiratory air-liquid interface cultures (ALI) from the porcine lung to analyze the interaction of streptococci with their primary target cells. As representative of the streptococcal family we chose Streptococcus suis (S. suis) that is not only a major swine respiratory pathogen but can also infect humans. Suilysin, a cholesterol-dependent cytolysin (CDC), is an important virulence factor. By comparing a S. suis wt strain with a suilysin-deficient mutant, we demonstrate that suilysin contributes to (i) adherence to airway cells (ii) loss of ciliated cells (iii) apoptosis, and (iv) invasion. Furthermore, we show that cytolytic activity of suilysin is crucial for these effects. A striking result of our analysis was the high efficiency of S. suis-induced apoptosis and invasion upon infection under ALI conditions. These properties have been reported to be less efficient when analyzed with immortalized cells. We hypothesize that soluble effectors such as suilysin are present at higher concentrations in cells kept at ALI conditions and thus more effective. These results should be relevant also for infection of the respiratory tract by other respiratory pathogens.",2016 May 27,"['Meng, Fandan', 'Wu, Nai-Huei', 'Seitz, Maren', 'Herrler, Georg', 'Valentin-Weigand, Peter']",Sci Rep,,,False
3f8d3e900290496401f7a6557a64255fdb3ebf0e,PMC,Protective effect of sildenafil on the genotoxicity and cytotoxicity in apolipoprotein E-deficient mice bone marrow cells,http://dx.doi.org/10.1186/s12944-016-0268-6,PMC4882816,27229150,CC BY,"BACKGROUND: The pharmacological inhibitor of phosphodiesterase 5 (PDE5), sildenafil, is a promising candidate for antioxidant therapy that can result in cardiovascular protection. In addition to its known effects on the cardiovascular system, hypercholesterolemia leads to increased oxidative stress and DNA damage in the bone marrow, which is a non-classical target organ of atherosclerosis. In the present study, we evaluate oxidative stress and assess the effect of genomic instability on cell cycle kinetics in atherosclerotic animals and determine if sildenafil reverses these detrimental effects in bone marrow cells. METHODS: Experiments were performed in male wild-type (WT) and apolipoprotein E knockout mice (apoE(−/−)) (9 weeks of age). apoE(−/−) mice were randomly distributed into the following 2 groups: sildenafil-treated (40 mg/kg/day for 3 weeks, n = 8) and vehicle-treated (n = 8), by oral gavage. After treatment, bone marrow cells were isolated to assess the production of superoxide anions and hydrogen peroxide, determine cell cycle kinetics and evaluate the presence of micronucleated cells. RESULTS: Sildenafil treatment reduced the cytoplasmic levels of superoxide anion (~95 % decrease, p < 0.05) and decreased hydrogen peroxide (~30 % decrease, p < 0.05). Moreover, we observed protective effects on the DNA of bone marrow cells, including normal cell cycling, decreased DNA fragmentation and a diminished frequency of micronucleated cells. CONCLUSION: Our data reveal that the excessive production of ROS in atherosclerotic mice overcome the DNA repair pathways in bone marrow cells. The novelty of the present study is that the administration of sildenafil reduced ROS to baseline levels and, consequently, reverted the DNA damage and its outcomes in bone marrow cells.",2016 May 27,"['Bernardes, Franciane P.', 'Batista, Alan T.', 'Porto, Marcella L.', 'Vasquez, Elisardo C.', 'Campagnaro, Bianca P.', 'Meyrelles, Silvana S.']",Lipids Health Dis,,,True
8a3678c3ee2208d7417bfdc62558fe0e32588eab,PMC,Complete Genome Sequence of Porcine Deltacoronavirus Isolated in Thailand in 2015,http://dx.doi.org/10.1128/genomeA.00408-16,PMC4882939,27231358,CC BY,"In Thailand, porcine deltacoronavirus (PDCoV) was first identified in November 2015. The virus was isolated from piglets experiencing diarrhea outbreak. Herein, the full-length genome sequence of the Thai PDCoV isolate P23_15_TT_1115 is reported. The results provide a clearer understanding of the molecular characteristics of PDCoV in Thailand.",2016 May 26,"['Madapong, Adthakorn', 'Saeng-chuto, Kepalee', 'Lorsirigool, Athip', 'Temeeyasen, Gun', 'Srijangwad, Anchalee', 'Tripipat, Thitima', 'Wegner, Matthew', 'Nilubol, Dachrit']",Genome Announc,,,True
6986e55cd9e5fd76339b6a6825b2c3069126555e,PMC,Molecular Epidemiological Investigation of Porcine kobuvirus and Its Coinfection Rate with PEDV and SaV in Northwest China,http://dx.doi.org/10.1155/2016/7590569,PMC4884858,27294133,CC BY,"Porcine kobuvirus (PKV) has circulated throughout China in recent years. Although many studies have detected it throughout the world, its molecular epidemiology has not been characterized in northwest China. To understand its prevalence, 203 fecal samples were collected from different regions of Gansu Province and tested with reverse transcription-polymerase chain reaction. In this study, we tested these samples for PKV, porcine epidemic diarrhea virus (PEDV), and sapovirus and analyzed the amplified 2C gene fragments of PKV. Overall, 126 (62.1%) samples were positive for PKV. Of the 74 piglets samples among the 203 fecal samples, 65 (87.8%) were positive for PKV. PKV infection was often accompanied by PEDV, but the relationship between the two viruses must be confirmed. A phylogenetic analysis indicated that the PKV strains isolated from the same regions clustered on the same branches. This investigation shows that PKV infections are highly prevalent in pigs in northwest China, especially in piglets with symptoms of diarrhea.",2016 May 16,"['Wang, Chen', 'Lan, Xi', 'Yang, Bin']",Biomed Res Int,,,True
0e8773d0887abfa54cb1b618fcdf491e7a0a2c8a,PMC,A Scorpion Defensin BmKDfsin4 Inhibits Hepatitis B Virus Replication in Vitro,http://dx.doi.org/10.3390/toxins8050124,PMC4885039,27128943,CC BY,"Hepatitis B virus (HBV) infection is a major worldwide health problem which can cause acute and chronic hepatitis and can significantly increase the risk of liver cirrhosis and primary hepatocellular carcinoma (HCC). Nowadays, clinical therapies of HBV infection still mainly rely on nucleotide analogs and interferons, the usage of which is limited by drug-resistant mutation or side effects. Defensins had been reported to effectively inhibit the proliferation of bacteria, fungi, parasites and viruses. Here, we screened the anti-HBV activity of 25 scorpion-derived peptides most recently characterized by our group. Through evaluating anti-HBV activity and cytotoxicity, we found that BmKDfsin4, a scorpion defensin with antibacterial and Kv1.3-blocking activities, has a comparable high inhibitory rate of both HBeAg and HBsAg in HepG2.2.15 culture medium and low cytotoxicity to HepG2.2.15. Then, our experimental results further showed that BmKDfsin4 can dose-dependently decrease the production of HBV DNA and HBV viral proteins in both culture medium and cell lysate. Interestingly, BmKDfsin4 exerted high serum stability. Together, this study indicates that the scorpion defensin BmKDfsin4 also has inhibitory activity against HBV replication along with its antibacterial and potassium ion channel Kv1.3-blocking activities, which shows that BmKDfsin4 is a uniquely multifunctional defensin molecule. Our work also provides a good molecule material which will be used to investigate the link or relationship of its antiviral, antibacterial and ion channel–modulating activities in the future.",2016 Apr 27,"['Zeng, Zhengyang', 'Zhang, Qian', 'Hong, Wei', 'Xie, Yingqiu', 'Liu, Yun', 'Li, Wenxin', 'Wu, Yingliang', 'Cao, Zhijian']",Toxins (Basel),,,True
1aac5ef2b73c3c93d866433ce1bb78ee956e2c45,PMC,A Scorpion Defensin BmKDfsin4 Inhibits Hepatitis B Virus Replication in Vitro,http://dx.doi.org/10.3390/toxins8050124,PMC4885039,27128943,CC BY,"Hepatitis B virus (HBV) infection is a major worldwide health problem which can cause acute and chronic hepatitis and can significantly increase the risk of liver cirrhosis and primary hepatocellular carcinoma (HCC). Nowadays, clinical therapies of HBV infection still mainly rely on nucleotide analogs and interferons, the usage of which is limited by drug-resistant mutation or side effects. Defensins had been reported to effectively inhibit the proliferation of bacteria, fungi, parasites and viruses. Here, we screened the anti-HBV activity of 25 scorpion-derived peptides most recently characterized by our group. Through evaluating anti-HBV activity and cytotoxicity, we found that BmKDfsin4, a scorpion defensin with antibacterial and Kv1.3-blocking activities, has a comparable high inhibitory rate of both HBeAg and HBsAg in HepG2.2.15 culture medium and low cytotoxicity to HepG2.2.15. Then, our experimental results further showed that BmKDfsin4 can dose-dependently decrease the production of HBV DNA and HBV viral proteins in both culture medium and cell lysate. Interestingly, BmKDfsin4 exerted high serum stability. Together, this study indicates that the scorpion defensin BmKDfsin4 also has inhibitory activity against HBV replication along with its antibacterial and potassium ion channel Kv1.3-blocking activities, which shows that BmKDfsin4 is a uniquely multifunctional defensin molecule. Our work also provides a good molecule material which will be used to investigate the link or relationship of its antiviral, antibacterial and ion channel–modulating activities in the future.",2016 Apr 27,"['Zeng, Zhengyang', 'Zhang, Qian', 'Hong, Wei', 'Xie, Yingqiu', 'Liu, Yun', 'Li, Wenxin', 'Wu, Yingliang', 'Cao, Zhijian']",Toxins (Basel),,,False
021fba0f252408868fa29b65686dedb3b3d6bf02,PMC,Isolation of the Binding Protein of Periplocoside E from BBMVs in Midgut of the Oriental Amyworm Mythimna separata Walker (Lepidoptera: Noctuidae) through Affinity Chromatography,http://dx.doi.org/10.3390/toxins8050139,PMC4885054,27153092,CC BY,"Periplocosides, which are insecticidal compounds isolated from the root bark of Periploca sepium Bunge, can affect the digestive system of insects. However, the mechanism though which periplocosides induces a series of symptoms remains unknown. In this study, affinity chromatography was conducted by coupling periplocoside E-semi-succinic acid ester with epoxy amino hexyl (EAH) sepharose 4B. Sodium dodecyl sulfonate-polyacrylamide gelelectrophoresis (SDS-PAGE) was performed to analyze the fraction eluted by periplocoside E. Eight binding proteins (luciferin 4-monooxygenase, aminopeptidase N, aminopeptidase N3, nicotinamide adenine dinucleotide health (NADH) dehydrogenase subunit 5, phosphatidylinositol 3-phosphate 3-phosphatase myotubularin, actin, uncharacterized family 31 glucosidase KIAA1161, and 2OG-Fe(2) oxygenase superfamily protein) were obtained and identified through liquid chromatography/quadrupole-time of flight-mass spectrometry (LC/Q-TOF-MS) analysis of the midgut epithelium cells of Mythimna separata larvae. Aminopeptidase N and N3 are potential putative targets of periplocosides. This study establishes the foundation for further research on the mechanism of action and target localization of periplocosides in agricultural pests.",2016 May 4,"['Feng, Mingxing', 'He, Zhenyu', 'Wang, Yuanyuan', 'Yan, Xiufang', 'Zhang, Jiwen', 'Hu, Zhaonong', 'Wu, Wenjun']",Toxins (Basel),,,True
367e3d844bd06915e08d9082a3b720dcc6ac845f,PMC,Dengue Virus Reporter Replicon is a Valuable Tool for Antiviral Drug Discovery and Analysis of Virus Replication Mechanisms,http://dx.doi.org/10.3390/v8050122,PMC4885077,27164125,CC BY,"Dengue, the most prevalent arthropod-borne viral disease, is caused by the dengue virus (DENV), a member of the Flaviviridae family, and is a considerable public health threat in over 100 countries, with 2.5 billion people living in high-risk areas. However, no specific antiviral drug or licensed vaccine currently targets DENV infection. The replicon system has all the factors needed for viral replication in cells. Since the development of replicon systems, transient and stable reporter replicons, as well as reporter viruses, have been used in the study of various virological aspects of DENV and in the identification of DENV inhibitors. In this review, we summarize the DENV reporter replicon system and its applications in high-throughput screening (HTS) for identification of anti-DENV inhibitors. We also describe the use of this system in elucidation of the mechanisms of virus replication and viral dynamics in vivo and in vitro.",2016 May 5,"['Kato, Fumihiro', 'Hishiki, Takayuki']",Viruses,,,True
6df7585dc7616c55baf0dd0df0a8a283f8805acd,PMC,Respiratory Syncytial Virus and Cellular Stress Responses: Impact on Replication and Physiopathology,http://dx.doi.org/10.3390/v8050124,PMC4885079,27187445,CC BY,"Human respiratory syncytial virus (RSV), a member of the Paramyxoviridae family, is a major cause of severe acute lower respiratory tract infection in infants, elderly and immunocompromised adults. Despite decades of research, a complete integrated picture of RSV-host interaction is still missing. Several cellular responses to stress are involved in the host-response to many virus infections. The endoplasmic reticulum stress induced by altered endoplasmic reticulum (ER) function leads to activation of the unfolded-protein response (UPR) to restore homeostasis. Formation of cytoplasmic stress granules containing translationally stalled mRNAs is a means to control protein translation. Production of reactive oxygen species is balanced by an antioxidant response to prevent oxidative stress and the resulting damages. In recent years, ongoing research has started to unveil specific regulatory interactions of RSV with these host cellular stress responses. Here, we discuss the latest findings regarding the mechanisms evolved by RSV to induce, subvert or manipulate the ER stress, the stress granule and oxidative stress responses. We summarize the evidence linking these stress responses with the regulation of RSV replication and the associated pathogenesis.",2016 May 12,"['Cervantes-Ortiz, Sandra L.', 'Zamorano Cuervo, Natalia', 'Grandvaux, Nathalie']",Viruses,,,True
790c6002db87c03cd6bdab85964c52808d09a218,PMC,Applications of Replicating-Competent Reporter-Expressing Viruses in Diagnostic and Molecular Virology,http://dx.doi.org/10.3390/v8050127,PMC4885082,27164126,CC BY,"Commonly used tests based on wild-type viruses, such as immunostaining, cannot meet the demands for rapid detection of viral replication, high-throughput screening for antivirals, as well as for tracking viral proteins or virus transport in real time. Notably, the development of replicating-competent reporter-expressing viruses (RCREVs) has provided an excellent option to detect directly viral replication without the use of secondary labeling, which represents a significant advance in virology. This article reviews the applications of RCREVs in diagnostic and molecular virology, including rapid neutralization tests, high-throughput screening systems, identification of viral receptors and virus-host interactions, dynamics of viral infections in vitro and in vivo, vaccination approaches and others. However, there remain various challenges associated with RCREVs, including pathogenicity alterations due to the insertion of a reporter gene, instability or loss of the reporter gene expression, or attenuation of reporter signals in vivo. Despite all these limitations, RCREVs have become powerful tools for both basic and applied virology with the development of new technologies for generating RCREVs, the inventions of novel reporters and the better understanding of regulation of viral replication.",2016 May 6,"['Li, Yongfeng', 'Li, Lian-Feng', 'Yu, Shaoxiong', 'Wang, Xiao', 'Zhang, Lingkai', 'Yu, Jiahui', 'Xie, Libao', 'Li, Weike', 'Ali, Razim', 'Qiu, Hua-Ji']",Viruses,,,True
a5bfd762a4fb6bdef664818c4e82ca3c718c8862,PMC,Use of Reporter Genes in the Generation of Vaccinia Virus-Derived Vectors,http://dx.doi.org/10.3390/v8050134,PMC4885089,27213433,CC BY,"Vaccinia virus (VACV) is one of the most extensively-studied viruses of the Poxviridae family. It is easy to genetically modify, so it has become a key tool for many applications. In this context, reporter genes facilitate the study of the role of foreign genes introduced into the genome of VACV. In this review, we describe the type of reporter genes that have been used to generate reporter-expressing VACV and the applications of the recombinant viruses obtained. Reporter-expressing VACV are currently employed in basic and immunology research, in the development of vaccines and cancer treatment.",2016 May 21,"['Al Ali, Sally', 'Baldanta, Sara', 'Fernández-Escobar, Mercedes', 'Guerra, Susana']",Viruses,,,True
7ba9c9ed2f4e80906b5fcdcd69b3537b3309f5e2,PMC,Mechanisms of Cellular Membrane Reorganization to Support Hepatitis C Virus Replication,http://dx.doi.org/10.3390/v8050142,PMC4885097,27213428,CC BY,"Like all positive-sense RNA viruses, hepatitis C virus (HCV) induces host membrane alterations for its replication termed the membranous web (MW). Assembling replication factors at a membranous structure might facilitate the processes necessary for genome replication and packaging and shield viral components from host innate immune defenses. The biogenesis of the HCV MW is a complex process involving a concerted effort of HCV nonstructural proteins with a growing list of host factors. Although a comprehensive understanding of MW formation is still missing, a number of important viral and host determinants have been identified. This review will summarize the recent studies that have led to our current knowledge of the role of viral and host factors in the biogenesis of the MWs and discuss how HCV uses this specialized membrane structure for its replication.",2016 May 20,"['Wang, Hongliang', 'Tai, Andrew W.']",Viruses,,,True
2d1d0fbb79973ccbe29af6ae067aa91d05599a4f,PMC,HACE1 Negatively Regulates Virus-Triggered Type I IFN Signaling by Impeding the Formation of the MAVS-TRAF3 Complex,http://dx.doi.org/10.3390/v8050146,PMC4885101,27213432,CC BY,"During virus infection, the cascade signaling pathway that leads to the production of proinflammatory cytokines is controlled at multiple levels to avoid detrimental overreaction. HACE1 has been characterized as an important tumor suppressor. Here, we identified HACE1 as an important negative regulator of virus-triggered type I IFN signaling. Overexpression of HACE1 inhibited Sendai virus- or poly (I:C)-induced signaling and resulted in reduced IFNB1 production and enhanced virus replication. Knockdown of HACE1 expression exhibited the opposite effects. Ubiquitin E3 ligase activity of the dead mutant HACE1/C876A had a comparable inhibitory function as WT HACE1, suggesting that the suppressive function of HACE1 on virus-induced signaling is independent of its E3 ligase activity. Further study indicated that HACE1 acted downstream of MAVS and upstream of TBK1. Mechanistic studies showed that HACE1 exerts its inhibitory role on virus-induced signaling by disrupting the MAVS-TRAF3 complex. Therefore, we uncovered a novel function of HACE1 in innate immunity regulation.",2016 May 21,"['Mao, He-Ting', 'Wang, Yan', 'Cai, Juan', 'Meng, Jun-Ling', 'Zhou, Yu', 'Pan, Yu', 'Qian, Xiao-Ping', 'Zhang, Yu', 'Zhang, Jun']",Viruses,,,True
740bbfc884c50507fbf78e9424da319a49c48af0,PMC,Para-Phenylenediamine Induces Apoptotic Death of Melanoma Cells and Reduces Melanoma Tumour Growth in Mice,http://dx.doi.org/10.1155/2016/3137010,PMC4886052,27293892,CC BY,"Melanoma is one of the most aggressive forms of cancer, usually resistant to standard chemotherapeutics. Despite a huge number of clinical trials, any success to find a chemotherapeutic agent that can effectively destroy melanoma is yet to be achieved. Para-phenylenediamine (p-PD) in the hair dyes is reported to purely serve as an external dyeing agent. Very little is known about whether p-PD has any effect on the melanin producing cells. We have demonstrated p-PD mediated apoptotic death of both human and mouse melanoma cells in vitro. Mouse melanoma tumour growth was also arrested by the apoptotic activity of intraperitoneal administration of p-PD with almost no side effects. This apoptosis is shown to occur primarily via loss of mitochondrial membrane potential (MMP), generation of reactive oxygen species (ROS), and caspase 8 activation. p-PD mediated apoptosis was also confirmed by the increase in sub-G0/G1 cell number. Thus, our experimental observation suggests that p-PD can be a potential less expensive candidate to be developed as a chemotherapeutic agent for melanoma.",2016 May 17,"['Bhowmick, Debajit', 'Bhar, Kaushik', 'Mallick, Sanjaya K.', 'Das, Subhadip', 'Chatterjee, Nabanita', 'Sarkar, Tuhin Subhra', 'Chakrabarti, Rajarshi', 'Das Saha, Krishna', 'Siddhanta, Anirban']",Biochem Res Int,,,True
75882d6856d4243248aa32fe119153efeb0dbe12,PMC,Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression,http://dx.doi.org/10.1128/JVI.02557-15,PMC4886784,27009955,CC BY,"Inflammation may be maladaptive to the control of viral infection when it impairs interferon (IFN) responses, enhancing viral replication and spread. Dysregulated immunity as a result of inappropriate innate inflammatory responses is a hallmark of chronic viral infections such as, hepatitis B virus and hepatitis C virus (HCV). Previous studies from our laboratory have shown that expression of an IFN-stimulated gene (ISG), ubiquitin-like protease (USP)18 is upregulated in chronic HCV infection, leading to impaired hepatocyte responses to IFN-α. We examined the ability of inflammatory stimuli, including tumor necrosis factor alpha (TNF-α), lipopolysaccharide (LPS), interleukin-6 (IL-6) and IL-10 to upregulate hepatocyte USP18 expression and blunt the IFN-α response. Human hepatoma cells and primary murine hepatocytes were treated with TNF-α/LPS/IL-6/IL-10 and USP18, phosphorylated (p)-STAT1 and myxovirus (influenza virus) resistance 1 (Mx1) expression was determined. Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-α, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-α refractory state, which was reversed by USP18 knockdown. Liver inflammation was induced in vivo using a murine model of hepatic ischemia/reperfusion injury. Hepatic ischemia/reperfusion injury led to an induction of USP18 expression in liver tissue and promotion of lymphocytic choriomeningitis replication. These data demonstrate that certain inflammatory stimuli (TNF-α and LPS) but not others (IL-6 and IL-10) target USP18 expression and thus inhibit IFN signaling. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with USP18 representing a potential target for intervention in various inflammatory states. IMPORTANCE Inflammation may prevent the control of viral infection when it impairs the innate immune response, enhancing viral replication and spread. Blunted immunity as a result of inappropriate innate inflammatory responses is a common characteristic of chronic viral infections. Previous studies have shown that expression of certain interferon-stimulated genes is upregulated in chronic HCV infection, leading to impaired hepatocyte responses. In this study, we show that multiple inflammatory stimuli can modulate interferon stimulated gene expression and thus inhibit hepatocyte interferon signaling via USP18 induction. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with the induction of USP18 representing a potential target for intervention in various inflammatory states.",2016 May 27,"['MacParland, Sonya A.', 'Ma, Xue-Zhong', 'Chen, Limin', 'Khattar, Ramzi', 'Cherepanov, Vera', 'Selzner, Markus', 'Feld, Jordan J.', 'Selzner, Nazia', 'McGilvray, Ian D.']",J Virol,,,True
dc7de10933e811946c548cca7b1f3dbe61161d13,PMC,Evolution-guided functional analyses reveal diverse antiviral specificities encoded by IFIT1 genes in mammals,http://dx.doi.org/10.7554/eLife.14228,PMC4887208,27240734,CC BY,"IFIT (interferon-induced with tetratricopeptide repeats) proteins are critical mediators of mammalian innate antiviral immunity. Mouse IFIT1 selectively inhibits viruses that lack 2'O-methylation of their mRNA 5' caps. Surprisingly, human IFIT1 does not share this antiviral specificity. Here, we resolve this discrepancy by demonstrating that human and mouse IFIT1 have evolved distinct functions using a combination of evolutionary, genetic and virological analyses. First, we show that human IFIT1 and mouse IFIT1 (renamed IFIT1B) are not orthologs, but are paralogs that diverged >100 mya. Second, using a yeast genetic assay, we show that IFIT1 and IFIT1B proteins differ in their ability to be suppressed by a cap 2'O-methyltransferase. Finally, we demonstrate that IFIT1 and IFIT1B have divergent antiviral specificities, including the discovery that only IFIT1 proteins inhibit a virus encoding a cap 2'O-methyltransferase. These functional data, combined with widespread turnover of mammalian IFIT genes, reveal dramatic species-specific differences in IFIT-mediated antiviral repertoires. DOI: http://dx.doi.org/10.7554/eLife.14228.001",,"['Daugherty, Matthew D', 'Schaller, Aaron M', 'Geballe, Adam P', 'Malik, Harmit S']",eLife.; 5:e14228,,,True
4ea6973e872fb9116a21c6539d2aba2ea5c1337c,PMC,Protein Kinase C-δ Mediates Shedding of Angiotensin-Converting Enzyme 2 from Proximal Tubular Cells,http://dx.doi.org/10.3389/fphar.2016.00146,PMC4887483,27313531,CC BY,"Angiotensin-converting enzyme 2 (ACE2) degrades angiotensin (Ang) II to Ang-(1–7), and protects against diabetic renal injury. Soluble ACE2 fragments are shed from the proximal tubule, and appear at high levels in the urine with diabetes. High glucose-induced shedding of ACE2 from proximal tubular cells is mediated by the enzyme “a disintegrin and metalloproteinase-17″ (ADAM17). Here, we investigated the mechanism for constitutive shedding of ACE2. Mouse proximal tubular cells were cultured and ACE2 shedding into the media was assessed by enzyme activity assay and immunoblot analysis. Cells were incubated with pharmacologic inhibitors, or transfected with silencing (si) RNA. Incubation of proximal tubular cells with increasing concentrations of D-glucose stimulated ACE2 shedding, which peaked at 16 mM, while L-glucose (osmotic control) had no effect on shedding. In cells maintained in 7.8 mM D-glucose, ACE2 shedding was significantly inhibited by the pan-protein kinase C (PKC) competitive inhibitor sotrastaurin, but not by an inhibitor of ADAM17. Incubation of cells with the PKC-α and -β1-specific inhibitor Go6976, the PKC β1 and β2-specific inhibitor ruboxistaurin, inhibitors of matrix metalloproteinases-2,-8, and -9, or an inhibitor of ADAM10 (GI250423X) had no effect on basal ACE2 shedding. By contrast, the PKC-δ inhibitor rottlerin significantly inhibited both constitutive and high glucose-induced ACE2 shedding. Transfection of cells with siRNA directed against PKC-δ reduced ACE2 shedding by 20%, while knockdown of PKC-ε was without effect. These results indicate that constitutive shedding of ACE2 from proximal tubular cells is mediated by PKC-δ, which is also linked to high glucose-induced shedding. Targeting PKC-δ may preserve membrane-bound ACE2 in proximal tubule in disease states and diminish Ang II-stimulated adverse signaling.",2016 Jun 1,"['Xiao, Fengxia', 'Zimpelmann, Joseph', 'Burger, Dylan', 'Kennedy, Christopher', 'Hébert, Richard L.', 'Burns, Kevin D.']",Front Pharmacol,,,True
364f3e45183f362e8398724c29d3b010436ce375,PMC,Biomarkers in Pediatric ARDS: Future Directions,http://dx.doi.org/10.3389/fped.2016.00055,PMC4887507,27313995,CC BY,"Acute respiratory distress syndrome (ARDS) is common among mechanically ventilated children and accompanies up to 30% of all pediatric intensive care unit deaths. Though ARDS diagnosis is based on clinical criteria, biological markers of acute lung damage have been extensively studied in adults and children. Biomarkers of inflammation, alveolar epithelial and capillary endothelial disruption, disordered coagulation, and associated derangements measured in the circulation and other body fluids, such as bronchoalveolar lavage, have improved our understanding of pathobiology of ARDS. The biochemical signature of ARDS has been increasingly well described in adult populations, and this has led to the identification of molecular phenotypes to augment clinical classifications. However, there is a paucity of data from pediatric ARDS (pARDS) patients. Biomarkers and molecular phenotypes have the potential to identify patients at high risk of poor outcomes, and perhaps inform the development of targeted therapies for specific groups of patients. Additionally, because of the lower incidence of and mortality from ARDS in pediatric patients relative to adults and lack of robust clinical predictors of outcome, there is an ongoing interest in biological markers as surrogate outcome measures. The recent definition of pARDS provides additional impetus for the measurement of established and novel biomarkers in future pediatric studies in order to further characterize this disease process. This chapter will review the currently available literature and discuss potential future directions for investigation into biomarkers in ARDS among children.",2016 Jun 1,"['Orwoll, Benjamin E.', 'Sapru, Anil']",Front Pediatr,,,True
c5df32e01e9583e1b4430418e8f8f58c8a85021c,PMC,Establishment and application of a real-time loop-mediated isothermal amplification system for the detection of CYP2C19 polymorphisms,http://dx.doi.org/10.1038/srep26533,PMC4887897,27246657,CC BY,"Single-nucleotide polymorphisms (SNPs) represent the most widespread type of genetic variation (approximately 90%) in the human genome, and the demand to overcome such variation has received more attention now than ever before. The capacity to rapidly assess SNPs that correlate with disease predisposition, drug efficacy and drug toxicity is a key step for the development of personalized medicine. In this work, a rapid one-step SNP detection method, real-time loop-mediated isothermal amplification (RT-LAMP), was first applied for CYP2C19 polymorphisms testing. The optimized method was established with specifically designed primers for target amplification by real-time detection in approximately 30 min under isothermal conditions. RT-LAMP amplified few copies of template to produce significant amounts of product and quantitatively detected human DNA with compatible specificity and sensitivity. The success in the establishment of this RT-LAMP protocol for CYP2C19 polymorphism testing is significant for the extension of this technique for the detection of other SNPs, which will further facilitate the development of personalized medicine.",2016 Jun 1,"['Zhang, Chao', 'Yao, Yao', 'Zhu, Juan-Li', 'Zhang, Si-Nong', 'Zhang, Shan-Shan', 'Wei, Hua', 'Hui, Wen-Li', 'Cui, Ya-Li']",Sci Rep,,,True
9363688452b649c407692622c30b4b5bc346c87e,PMC,Establishment and application of a real-time loop-mediated isothermal amplification system for the detection of CYP2C19 polymorphisms,http://dx.doi.org/10.1038/srep26533,PMC4887897,27246657,CC BY,"Single-nucleotide polymorphisms (SNPs) represent the most widespread type of genetic variation (approximately 90%) in the human genome, and the demand to overcome such variation has received more attention now than ever before. The capacity to rapidly assess SNPs that correlate with disease predisposition, drug efficacy and drug toxicity is a key step for the development of personalized medicine. In this work, a rapid one-step SNP detection method, real-time loop-mediated isothermal amplification (RT-LAMP), was first applied for CYP2C19 polymorphisms testing. The optimized method was established with specifically designed primers for target amplification by real-time detection in approximately 30 min under isothermal conditions. RT-LAMP amplified few copies of template to produce significant amounts of product and quantitatively detected human DNA with compatible specificity and sensitivity. The success in the establishment of this RT-LAMP protocol for CYP2C19 polymorphism testing is significant for the extension of this technique for the detection of other SNPs, which will further facilitate the development of personalized medicine.",2016 Jun 1,"['Zhang, Chao', 'Yao, Yao', 'Zhu, Juan-Li', 'Zhang, Si-Nong', 'Zhang, Shan-Shan', 'Wei, Hua', 'Hui, Wen-Li', 'Cui, Ya-Li']",Sci Rep,,,False
92ced556ed66213053dfc7abfa35deb9c1f8ef8e,PMC,"Is the global health community prepared for future pandemics? A need for solidarity, resources and strong governance",http://dx.doi.org/10.15252/emmm.201606337,PMC4888848,27137494,CC BY,"In the wake of recent outbreaks of Zika, Ebola and the MERS‐CoV viruses, many are asking: how prepared is the global public health community to deal with future emerging pandemics? Collective action at national, regional and global levels is the best way forward. [Image: see text]",2016 Jun 21,"Pang, Tikki",EMBO Mol Med,,,True
91c146beba875fde88ed4e4770cfb6325ad2f038,PMC,HTCC: Broad Range Inhibitor of Coronavirus Entry,http://dx.doi.org/10.1371/journal.pone.0156552,PMC4889042,27249425,CC BY,"To date, six human coronaviruses have been known, all of which are associated with respiratory infections in humans. With the exception of the highly pathogenic SARS and MERS coronaviruses, human coronaviruses (HCoV-NL63, HCoV-OC43, HCoV-229E, and HCoV-HKU1) circulate worldwide and typically cause the common cold. In most cases, infection with these viruses does not lead to severe disease, although acute infections in infants, the elderly, and immunocompromised patients may progress to severe disease requiring hospitalization. Importantly, no drugs against human coronaviruses exist, and only supportive therapy is available. Previously, we proposed the cationically modified chitosan, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), and its hydrophobically-modified derivative (HM-HTCC) as potent inhibitors of the coronavirus HCoV-NL63. Here, we show that HTCC inhibits interaction of a virus with its receptor and thus blocks the entry. Further, we demonstrate that HTCC polymers with different degrees of substitution act as effective inhibitors of all low-pathogenic human coronaviruses.",2016 Jun 1,"['Milewska, Aleksandra', 'Kaminski, Kamil', 'Ciejka, Justyna', 'Kosowicz, Katarzyna', 'Zeglen, Slawomir', 'Wojarski, Jacek', 'Nowakowska, Maria', 'Szczubiałka, Krzysztof', 'Pyrc, Krzysztof']",PLoS One,,,True
dbf76534e0b330bb0f155296e251c1e7031c90c0,PMC,The Respiratory Protection Effectiveness Clinical Trial (ResPECT): a cluster-randomized comparison of respirator and medical mask effectiveness against respiratory infections in healthcare personnel,http://dx.doi.org/10.1186/s12879-016-1494-2,PMC4890247,27255755,CC BY,"BACKGROUND: Although N95 filtering facepiece respirators and medical masks are commonly used for protection against respiratory infections in healthcare settings, more clinical evidence is needed to understand the optimal settings and exposure circumstances for healthcare personnel to use these devices. A lack of clinically germane research has led to equivocal, and occasionally conflicting, healthcare respiratory protection recommendations from public health organizations, professional societies, and experts. METHODS: The Respiratory Protection Effectiveness Clinical Trial (ResPECT) is a prospective comparison of respiratory protective equipment to be conducted at multiple U.S. study sites. Healthcare personnel who work in outpatient settings will be cluster-randomized to wear N95 respirators or medical masks for protection against infections during respiratory virus season. Outcome measures will include laboratory-confirmed viral respiratory infections, acute respiratory illness, and influenza-like illness. Participant exposures to patients, coworkers, and others with symptoms and signs of respiratory infection, both within and beyond the workplace, will be recorded in daily diaries. Adherence to study protocols will be monitored by the study team. DISCUSSION: ResPECT is designed to better understand the extent to which N95s and MMs reduce clinical illness among healthcare personnel. A fully successful study would produce clinically relevant results that help clinician-leaders make reasoned decisions about protection of healthcare personnel against occupationally acquired respiratory infections and prevention of spread within healthcare systems. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov, number NCT01249625 (11/29/2010).",2016 Jun 2,"['Radonovich, Lewis J.', 'Bessesen, Mary T.', 'Cummings, Derek A.', 'Eagan, Aaron', 'Gaydos, Charlotte', 'Gibert, Cynthia', 'Gorse, Geoffrey J.', 'Nyquist, Ann-Christine', 'Reich, Nicholas G.', 'Rodrigues-Barradas, Maria', 'Savor-Price, Connie', 'Shaffer, Ronald E.', 'Simberkoff, Michael S.', 'Perl, Trish M.']",BMC Infect Dis,,,True
a85a6d90b479fd8547830827ec8898750794cdf3,PMC,Autophagy: New Questions from Recent Answers,http://dx.doi.org/10.5402/2012/738718,PMC4890908,27335669,CC BY,"Macroautophagy (hereafter autophagy) is currently one of the areas of medical life sciences attracting a great interest because of its pathological implications and therapy potentials. The discovery of the autophagy-related genes (ATGs) has been the key event in this research field because their study has led to the acquisition of new knowledge about the mechanism of this transport pathway. In addition, the investigation of these genes in numerous model systems has revealed the central role that autophagy plays in maintaining the cell homeostasis. This process carries out numerous physiological functions, some of which were unpredicted and thus surprising. Here, we will review some of the questions about the mechanism and function of autophagy that still remain unanswered, and new ones that have emerged from the recent discoveries.",2012 Dec 30,"Reggiori, Fulvio",ISRN Mol Biol,,,True
e447d139f1d046120a293f1219944e82c77bc829,PMC,"Oblongifolin M, an active compound isolated from a Chinese medical herb Garcinia oblongifolia, potently inhibits enterovirus 71 reproduction through downregulation of ERp57",http://dx.doi.org/10.18632/oncotarget.7122,PMC4891005,26848777,CC BY,"There is no effective drug to treat EV71 infection yet. Traditional Chinese herbs are great resources for novel antiviral compounds. Here we showed that Oblongifolin M (OM), an active compound isolated from Garcinia oblongifolia, potently inhibited EV71 infection in a dose dependent manner. To identify its potential effectors in the host cells, we successfully identified 18 proteins from 52 differentially expressed spots by comparative proteomics studies. Further studies showed that knockdown of ERp57 inhibited viral replication through downregulating viral IRES (internal ribosome entry site) activities, whereas ectopic expression of ERp57 increased IRES activity and partly rescued the inhibitory effects of OM on viral replication. We demonstrated that OM is an effective antiviral agent; and that ERp57 is one of its cellular effectors against EV71 infection.",2016 Feb 1,"['Wang, Mengjie', 'Dong, Qi', 'Wang, Hua', 'He, Yaqing', 'Chen, Ying', 'Zhang, Hong', 'Wu, Rong', 'Chen, Xinchun', 'Zhou, Boping', 'He, Jason', 'Kung, Hsiang-Fu', 'Huang, Canhua', 'Wei, Yuquan', 'Huang, Jian-dong', 'Xu, Hongxi', 'He, Ming-Liang']",Oncotarget,,,True
8fae4d1f513f03412a39c288a957fe5573c48b41,PMC,"Oblongifolin M, an active compound isolated from a Chinese medical herb Garcinia oblongifolia, potently inhibits enterovirus 71 reproduction through downregulation of ERp57",http://dx.doi.org/10.18632/oncotarget.7122,PMC4891005,26848777,CC BY,"There is no effective drug to treat EV71 infection yet. Traditional Chinese herbs are great resources for novel antiviral compounds. Here we showed that Oblongifolin M (OM), an active compound isolated from Garcinia oblongifolia, potently inhibited EV71 infection in a dose dependent manner. To identify its potential effectors in the host cells, we successfully identified 18 proteins from 52 differentially expressed spots by comparative proteomics studies. Further studies showed that knockdown of ERp57 inhibited viral replication through downregulating viral IRES (internal ribosome entry site) activities, whereas ectopic expression of ERp57 increased IRES activity and partly rescued the inhibitory effects of OM on viral replication. We demonstrated that OM is an effective antiviral agent; and that ERp57 is one of its cellular effectors against EV71 infection.",2016 Feb 1,"['Wang, Mengjie', 'Dong, Qi', 'Wang, Hua', 'He, Yaqing', 'Chen, Ying', 'Zhang, Hong', 'Wu, Rong', 'Chen, Xinchun', 'Zhou, Boping', 'He, Jason', 'Kung, Hsiang-Fu', 'Huang, Canhua', 'Wei, Yuquan', 'Huang, Jian-dong', 'Xu, Hongxi', 'He, Ming-Liang']",Oncotarget,,,False
ada981b0b99f2468f331107ff419b9aea9c9175e,PMC,Extensive coronavirus-induced membrane rearrangements are not a determinant of pathogenicity,http://dx.doi.org/10.1038/srep27126,PMC4891661,27255716,CC BY,"Positive-strand RNA (+RNA) viruses rearrange cellular membranes during replication, possibly in order to concentrate and arrange viral replication machinery for efficient viral RNA synthesis. Our previous work showed that in addition to the conserved coronavirus double membrane vesicles (DMVs), Beau-R, an apathogenic strain of avian Gammacoronavirus infectious bronchitis virus (IBV), induces regions of ER that are zippered together and tethered open-necked double membrane spherules that resemble replication organelles induced by other +RNA viruses. Here we compared structures induced by Beau-R with the pathogenic lab strain M41 to determine whether membrane rearrangements are strain dependent. Interestingly, M41 was found to have a low spherule phenotype. We then compared a panel of pathogenic, mild and attenuated IBV strains in ex vivo tracheal organ culture (TOC). Although the low spherule phenotype of M41 was conserved in TOCs, each of the other tested IBV strains produced DMVs, zippered ER and spherules. Furthermore, there was a significant correlation for the presence of DMVs with spherules, suggesting that these structures are spatially and temporally linked. Our data indicate that virus induced membrane rearrangements are fundamentally linked to the viral replicative machinery. However, coronavirus replicative apparatus clearly has the plasticity to function in different structural contexts.",2016 Jun 3,"['Maier, Helena J.', 'Neuman, Benjamin W.', 'Bickerton, Erica', 'Keep, Sarah M.', 'Alrashedi, Hasan', 'Hall, Ross', 'Britton, Paul']",Sci Rep,,,True
3f23cb13bcb298f25433f191853049d2fa904565,PMC,Extensive coronavirus-induced membrane rearrangements are not a determinant of pathogenicity,http://dx.doi.org/10.1038/srep27126,PMC4891661,27255716,CC BY,"Positive-strand RNA (+RNA) viruses rearrange cellular membranes during replication, possibly in order to concentrate and arrange viral replication machinery for efficient viral RNA synthesis. Our previous work showed that in addition to the conserved coronavirus double membrane vesicles (DMVs), Beau-R, an apathogenic strain of avian Gammacoronavirus infectious bronchitis virus (IBV), induces regions of ER that are zippered together and tethered open-necked double membrane spherules that resemble replication organelles induced by other +RNA viruses. Here we compared structures induced by Beau-R with the pathogenic lab strain M41 to determine whether membrane rearrangements are strain dependent. Interestingly, M41 was found to have a low spherule phenotype. We then compared a panel of pathogenic, mild and attenuated IBV strains in ex vivo tracheal organ culture (TOC). Although the low spherule phenotype of M41 was conserved in TOCs, each of the other tested IBV strains produced DMVs, zippered ER and spherules. Furthermore, there was a significant correlation for the presence of DMVs with spherules, suggesting that these structures are spatially and temporally linked. Our data indicate that virus induced membrane rearrangements are fundamentally linked to the viral replicative machinery. However, coronavirus replicative apparatus clearly has the plasticity to function in different structural contexts.",2016 Jun 3,"['Maier, Helena J.', 'Neuman, Benjamin W.', 'Bickerton, Erica', 'Keep, Sarah M.', 'Alrashedi, Hasan', 'Hall, Ross', 'Britton, Paul']",Sci Rep,,,False
97699e1e790ab279013460ac4478cc6b9832d2e1,PMC,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) origin and animal reservoir,http://dx.doi.org/10.1186/s12985-016-0544-0,PMC4891877,27255185,CC BY,"Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans. Though not confirmed yet, multiple surveillance and phylogenetic studies suggest a bat origin. The disease is heavily endemic in dromedary camel populations of East Africa and the Middle East. It is unclear as to when the virus was introduced to dromedary camels, but data from studies that investigated stored dromedary camel sera and geographical distribution of involved dromedary camel populations suggested that the virus was present in dromedary camels several decades ago. Though bats and alpacas can serve as potential reservoirs for MERS-CoV, dromedary camels seem to be the only animal host responsible for the spill over human infections.",2016 Jun 3,"['Mohd, Hamzah A.', 'Al-Tawfiq, Jaffar A.', 'Memish, Ziad A.']",Virol J,,,True
945fd47a82b49774675d732d27f6b806c0e6aeb1,PMC,Nonhuman Primate IFITM Proteins Are Potent Inhibitors of HIV and SIV,http://dx.doi.org/10.1371/journal.pone.0156739,PMC4892622,27257969,CC BY,"Interferon-induced transmembrane (IFITM) proteins are potent antiviral factors shown to restrict the infection of many enveloped viruses, including HIV. Here we report cloning and characterization of a panel of nonhuman primate IFITMs. We show that, similar to human IFITM, nonhuman primate IFITM proteins inhibit HIV and other primate lentiviruses. While some nonhuman primate IFITM proteins are more potent than human counterparts to inhibit HIV-1, they are generally not effective against HIV-2 similar to that of human IFITMs. Notably, depending on SIV strains and also IFITM species tested, nonhuman primate IFITM proteins exhibit distinct activities against SIVs; no correlation was found to support the notion that IFITM proteins are most active in non-natural primate hosts. Consistent with our recent findings for human IFITMs, nonhuman primate IFITM proteins interact with HIV-1 Env and strongly act in viral producer cells to impair viral infectivity and block cell-to-cell transmission. Accordingly, knockdown of primate IFITM3 increases HIV-1 replication in nohuman primate cells. Interestingly, analysis of DNA sequences of human and nonhuman primate IFITMs suggest that IFITM proteins have been undergoing purifying selection, rather than positive selection typical for cellular restriction factors. Overall, our study reveals some new and unexpected features of IFITMs in restricting primate lentiviruses, which enhances our understanding of virus-host interaction and AIDS pathogenesis.",2016 Jun 3,"['Wilkins, Jordan', 'Zheng, Yi-Min', 'Yu, Jingyou', 'Liang, Chen', 'Liu, Shan-Lu']",PLoS One,,,True
2e28d846c5181c13e9ff54ef725fb009dd966b47,PMC,Severe maternal morbidity due to respiratory disease and impact of 2009 H1N1 influenza A pandemic in Brazil: results from a national multicenter cross-sectional study,http://dx.doi.org/10.1186/s12879-016-1525-z,PMC4894555,27207244,CC BY,"BACKGROUND: The aim of this study was to assess the burden of respiratory disease, considering the influenza A pandemic season (H1N1pdm09), within the Brazilian Network for Surveillance of Severe Maternal Morbidity, and factors associated with worse maternal outcome. METHODS: A multicenter cross-sectional study, involving 27 referral maternity hospitals in five Brazilian regions. Cases were identified in a prospective surveillance by using the WHO standardized criteria for potentially life-threatening conditions (PLTC) and maternal near miss (MNM). Women with severe complications from respiratory disease identified as suspected or confirmed cases of H1N1 influenza or respiratory failure were compared to those with other causes of severe morbidity. A review of suspected H1N1 influenza cases classified women as non-tested, tested positive and tested negative, comparing their outcomes. Factors associated with severe maternal outcome (SMO = MNM + MD) were assessed in both groups, in comparison to PLTC, using PR and 95 % CI adjusted for design effect of cluster sampling. RESULTS: Among 9555 cases of severe maternal morbidity, 485 (5 %) had respiratory disease. Respiratory disease occurred in one-quarter of MNM cases and two-thirds of MD. H1N1 virus was suspected in 206 cases with respiratory illness. Around 60 % of these women were tested, yielding 49 confirmed cases. Confirmed H1N1 influenza cases had worse adverse outcomes (MNM:MD ratio < 1 (0.9:1), compared to 12:1 in cases due to other causes), and a mortality index > 50 %, in comparison to 7.4 % in other causes of severe maternal morbidity. Delay in medical care was associated with SMO in all cases considered, with a two-fold increased risk among respiratory disease patients. Perinatal outcome was worse in cases complicated by respiratory disease, with increased prematurity, stillbirth, low birth weight and Apgar score < 7. CONCLUSIONS: Respiratory disease, especially considering the influenza season, is a very severe cause of maternal near miss and death. Increased awareness about this condition, preventive vaccination during pregnancy, early diagnosis and treatment are required to improve maternal health.",2016 May 21,"['Pfitscher, L. C.', 'Cecatti, J. G.', 'Pacagnella, R. C.', 'Haddad, S. M.', 'Parpinelli, M. A.', 'Souza, J. P.', 'Quintana, S. M.', 'Surita, F. G.', 'Sousa, M. H.', 'Costa, M. L.', None]",BMC Infect Dis,,,True
b8a27d9cc6b79620fefffaf23778c2d799248682,PMC,Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data,http://dx.doi.org/10.1371/journal.pcbi.1004876,PMC4894584,27271698,CC BY,"The estimation of disease prevalence in online search engine data (e.g., Google Flu Trends (GFT)) has received a considerable amount of scholarly and public attention in recent years. While the utility of search engine data for disease surveillance has been demonstrated, the scientific community still seeks ways to identify and reduce biases that are embedded in search engine data. The primary goal of this study is to explore new ways of improving the accuracy of disease prevalence estimations by combining traditional disease data with search engine data. A novel method, Biased Sentinel Hospital-based Area Disease Estimation (B-SHADE), is introduced to reduce search engine data bias from a geographical perspective. To monitor search trends on Hand, Foot and Mouth Disease (HFMD) in Guangdong Province, China, we tested our approach by selecting 11 keywords from the Baidu index platform, a Chinese big data analyst similar to GFT. The correlation between the number of real cases and the composite index was 0.8. After decomposing the composite index at the city level, we found that only 10 cities presented a correlation of close to 0.8 or higher. These cities were found to be more stable with respect to search volume, and they were selected as sample cities in order to estimate the search volume of the entire province. After the estimation, the correlation improved from 0.8 to 0.864. After fitting the revised search volume with historical cases, the mean absolute error was 11.19% lower than it was when the original search volume and historical cases were combined. To our knowledge, this is the first study to reduce search engine data bias levels through the use of rigorous spatial sampling strategies.",2016 Jun 6,"['Huang, Da-Cang', 'Wang, Jin-Feng', 'Huang, Ji-Xia', 'Sui, Daniel Z.', 'Zhang, Hong-Yan', 'Hu, Mao-Gui', 'Xu, Cheng-Dong']",PLoS Comput Biol,,,True
9bb4db31c5490bc2f6f5e3c54d3a2ed7ce69048a,PMC,Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data,http://dx.doi.org/10.1371/journal.pcbi.1004876,PMC4894584,27271698,CC BY,"The estimation of disease prevalence in online search engine data (e.g., Google Flu Trends (GFT)) has received a considerable amount of scholarly and public attention in recent years. While the utility of search engine data for disease surveillance has been demonstrated, the scientific community still seeks ways to identify and reduce biases that are embedded in search engine data. The primary goal of this study is to explore new ways of improving the accuracy of disease prevalence estimations by combining traditional disease data with search engine data. A novel method, Biased Sentinel Hospital-based Area Disease Estimation (B-SHADE), is introduced to reduce search engine data bias from a geographical perspective. To monitor search trends on Hand, Foot and Mouth Disease (HFMD) in Guangdong Province, China, we tested our approach by selecting 11 keywords from the Baidu index platform, a Chinese big data analyst similar to GFT. The correlation between the number of real cases and the composite index was 0.8. After decomposing the composite index at the city level, we found that only 10 cities presented a correlation of close to 0.8 or higher. These cities were found to be more stable with respect to search volume, and they were selected as sample cities in order to estimate the search volume of the entire province. After the estimation, the correlation improved from 0.8 to 0.864. After fitting the revised search volume with historical cases, the mean absolute error was 11.19% lower than it was when the original search volume and historical cases were combined. To our knowledge, this is the first study to reduce search engine data bias levels through the use of rigorous spatial sampling strategies.",2016 Jun 6,"['Huang, Da-Cang', 'Wang, Jin-Feng', 'Huang, Ji-Xia', 'Sui, Daniel Z.', 'Zhang, Hong-Yan', 'Hu, Mao-Gui', 'Xu, Cheng-Dong']",PLoS Comput Biol,,,True
6660c114ae3ea21b9a1551e9253d767d5b7ae9f7,PMC,Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data,http://dx.doi.org/10.1371/journal.pcbi.1004876,PMC4894584,27271698,CC BY,"The estimation of disease prevalence in online search engine data (e.g., Google Flu Trends (GFT)) has received a considerable amount of scholarly and public attention in recent years. While the utility of search engine data for disease surveillance has been demonstrated, the scientific community still seeks ways to identify and reduce biases that are embedded in search engine data. The primary goal of this study is to explore new ways of improving the accuracy of disease prevalence estimations by combining traditional disease data with search engine data. A novel method, Biased Sentinel Hospital-based Area Disease Estimation (B-SHADE), is introduced to reduce search engine data bias from a geographical perspective. To monitor search trends on Hand, Foot and Mouth Disease (HFMD) in Guangdong Province, China, we tested our approach by selecting 11 keywords from the Baidu index platform, a Chinese big data analyst similar to GFT. The correlation between the number of real cases and the composite index was 0.8. After decomposing the composite index at the city level, we found that only 10 cities presented a correlation of close to 0.8 or higher. These cities were found to be more stable with respect to search volume, and they were selected as sample cities in order to estimate the search volume of the entire province. After the estimation, the correlation improved from 0.8 to 0.864. After fitting the revised search volume with historical cases, the mean absolute error was 11.19% lower than it was when the original search volume and historical cases were combined. To our knowledge, this is the first study to reduce search engine data bias levels through the use of rigorous spatial sampling strategies.",2016 Jun 6,"['Huang, Da-Cang', 'Wang, Jin-Feng', 'Huang, Ji-Xia', 'Sui, Daniel Z.', 'Zhang, Hong-Yan', 'Hu, Mao-Gui', 'Xu, Cheng-Dong']",PLoS Comput Biol,,,False
c43ec4dfe55ad2ad03d889319eff02fbbec582f8,PMC,Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data,http://dx.doi.org/10.1371/journal.pcbi.1004876,PMC4894584,27271698,CC BY,"The estimation of disease prevalence in online search engine data (e.g., Google Flu Trends (GFT)) has received a considerable amount of scholarly and public attention in recent years. While the utility of search engine data for disease surveillance has been demonstrated, the scientific community still seeks ways to identify and reduce biases that are embedded in search engine data. The primary goal of this study is to explore new ways of improving the accuracy of disease prevalence estimations by combining traditional disease data with search engine data. A novel method, Biased Sentinel Hospital-based Area Disease Estimation (B-SHADE), is introduced to reduce search engine data bias from a geographical perspective. To monitor search trends on Hand, Foot and Mouth Disease (HFMD) in Guangdong Province, China, we tested our approach by selecting 11 keywords from the Baidu index platform, a Chinese big data analyst similar to GFT. The correlation between the number of real cases and the composite index was 0.8. After decomposing the composite index at the city level, we found that only 10 cities presented a correlation of close to 0.8 or higher. These cities were found to be more stable with respect to search volume, and they were selected as sample cities in order to estimate the search volume of the entire province. After the estimation, the correlation improved from 0.8 to 0.864. After fitting the revised search volume with historical cases, the mean absolute error was 11.19% lower than it was when the original search volume and historical cases were combined. To our knowledge, this is the first study to reduce search engine data bias levels through the use of rigorous spatial sampling strategies.",2016 Jun 6,"['Huang, Da-Cang', 'Wang, Jin-Feng', 'Huang, Ji-Xia', 'Sui, Daniel Z.', 'Zhang, Hong-Yan', 'Hu, Mao-Gui', 'Xu, Cheng-Dong']",PLoS Comput Biol,,,False
8ca4fb44ca22975a061b3cc8a164f11466c4906d,PMC,Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data,http://dx.doi.org/10.1371/journal.pcbi.1004876,PMC4894584,27271698,CC BY,"The estimation of disease prevalence in online search engine data (e.g., Google Flu Trends (GFT)) has received a considerable amount of scholarly and public attention in recent years. While the utility of search engine data for disease surveillance has been demonstrated, the scientific community still seeks ways to identify and reduce biases that are embedded in search engine data. The primary goal of this study is to explore new ways of improving the accuracy of disease prevalence estimations by combining traditional disease data with search engine data. A novel method, Biased Sentinel Hospital-based Area Disease Estimation (B-SHADE), is introduced to reduce search engine data bias from a geographical perspective. To monitor search trends on Hand, Foot and Mouth Disease (HFMD) in Guangdong Province, China, we tested our approach by selecting 11 keywords from the Baidu index platform, a Chinese big data analyst similar to GFT. The correlation between the number of real cases and the composite index was 0.8. After decomposing the composite index at the city level, we found that only 10 cities presented a correlation of close to 0.8 or higher. These cities were found to be more stable with respect to search volume, and they were selected as sample cities in order to estimate the search volume of the entire province. After the estimation, the correlation improved from 0.8 to 0.864. After fitting the revised search volume with historical cases, the mean absolute error was 11.19% lower than it was when the original search volume and historical cases were combined. To our knowledge, this is the first study to reduce search engine data bias levels through the use of rigorous spatial sampling strategies.",2016 Jun 6,"['Huang, Da-Cang', 'Wang, Jin-Feng', 'Huang, Ji-Xia', 'Sui, Daniel Z.', 'Zhang, Hong-Yan', 'Hu, Mao-Gui', 'Xu, Cheng-Dong']",PLoS Comput Biol,,,False
ae94b6a3da2521778ce8af0fe653a30a14f74c6a,PMC,Zika Virus Focuses the Gain-of-Function Debate,http://dx.doi.org/10.1128/mSphere.00069-16,PMC4894681,27303723,CC BY,,2016 Apr 6,"['Imperiale, Michael J.', 'Casadevall, Arturo']",mSphere,,,True
a3c43cf529fc26a2f6b039c7e2aa9f0825a9a19f,PMC,A Single Residue in Ebola Virus Receptor NPC1 Influences Cellular Host Range in Reptiles,http://dx.doi.org/10.1128/mSphere.00007-16,PMC4894689,27303731,CC BY,"Filoviruses are the causative agents of an increasing number of disease outbreaks in human populations, including the current unprecedented Ebola virus disease (EVD) outbreak in western Africa. One obstacle to controlling these epidemics is our poor understanding of the host range of filoviruses and their natural reservoirs. Here, we investigated the role of the intracellular filovirus receptor, Niemann-Pick C1 (NPC1) as a molecular determinant of Ebola virus (EBOV) host range at the cellular level. Whereas human cells can be infected by EBOV, a cell line derived from a Russell’s viper (Daboia russellii) (VH-2) is resistant to infection in an NPC1-dependent manner. We found that VH-2 cells are resistant to EBOV infection because the Russell’s viper NPC1 ortholog bound poorly to the EBOV spike glycoprotein (GP). Analysis of panels of viper-human NPC1 chimeras and point mutants allowed us to identify a single amino acid residue in NPC1, at position 503, that bidirectionally influenced both its binding to EBOV GP and its viral receptor activity in cells. Significantly, this single residue change perturbed neither NPC1’s endosomal localization nor its housekeeping role in cellular cholesterol trafficking. Together with other recent work, these findings identify sequences in NPC1 that are important for viral receptor activity by virtue of their direct interaction with EBOV GP and suggest that they may influence filovirus host range in nature. Broader surveys of NPC1 orthologs from vertebrates may delineate additional sequence polymorphisms in this gene that control susceptibility to filovirus infection. IMPORTANCE Identifying cellular factors that determine susceptibility to infection can help us understand how Ebola virus is transmitted. We asked if the EBOV receptor Niemann-Pick C1 (NPC1) could explain why reptiles are resistant to EBOV infection. We demonstrate that cells derived from the Russell’s viper are not susceptible to infection because EBOV cannot bind to viper NPC1. This resistance to infection can be mapped to a single amino acid residue in viper NPC1 that renders it unable to bind to EBOV GP. The newly solved structure of EBOV GP bound to NPC1 confirms our findings, revealing that this residue dips into the GP receptor-binding pocket and is therefore critical to the binding interface. Consequently, this otherwise well-conserved residue in vertebrate species influences the ability of reptilian NPC1 proteins to bind to EBOV GP, thereby affecting viral host range in reptilian cells.",2016 Mar 30,"['Ndungo, Esther', 'Herbert, Andrew S.', 'Raaben, Matthijs', 'Obernosterer, Gregor', 'Biswas, Rohan', 'Miller, Emily Happy', 'Wirchnianski, Ariel S.', 'Carette, Jan E.', 'Brummelkamp, Thijn R.', 'Whelan, Sean P.', 'Dye, John M.', 'Chandran, Kartik']",mSphere,,,True
4997e92b014bb26f8184eae26662a09ffcf4f733,PMC,DGV: Dengue Genographic Viewer,http://dx.doi.org/10.3389/fmicb.2016.00875,PMC4894901,27375595,CC BY,"Dengue viruses (DENVs) and their vectors are widely distributed throughout the tropical and subtropical regions of the world. An autochthonous case of DENV was reported in Tokyo, Japan, in 2014, for the first time in 70 years. A comprehensive database of DENV sequences containing both serotype and genotype data and epidemiological data is crucial to trace DENV outbreak isolates and promptly respond to outbreaks. We constructed a DENV database containing the serotype, genotype, year and country/region of collection by collecting all publically available DENV sequence information from the National Center for Biotechnology Information (NCBI) and assigning genotype information. We also implemented the web service Dengue Genographic Viewer (DGV), which shows the geographical distribution of each DENV genotype in a user-specified time span. DGV also assigns the serotype and genotype to a user-specified sequence by performing a homology search against the curated DENV database, and shows its homologous sequences with the geographical position and year of collection. DGV also shows the distribution of DENV-infected entrants to Japan by plotting epidemiological data from the Infectious Agents Surveillance Report (IASR), Japan. This overview of the DENV genotype distribution may aid in planning for the control of DENV infections. DGV is freely available online at: (https://gph.niid.go.jp/geograph/dengue/content/genomemap).",2016 Jun 7,"['Yamashita, Akifumi', 'Sakamoto, Tetsuya', 'Sekizuka, Tsuyoshi', 'Kato, Kengo', 'Takasaki, Tomohiko', 'Kuroda, Makoto']",Front Microbiol,,,True
7ba06e5c566af08208ee7d87cc8a0d6c2b772b9e,PMC,"Transmission of Hand, Foot and Mouth Disease and Its Potential Driving Factors in Hong Kong",http://dx.doi.org/10.1038/srep27500,PMC4895171,27271966,CC BY,"Hand-foot-and-mouth disease (HFMD) is a common childhood disease with substantial disease burden in Asia. Mixed results were reported on the associations between HFMD incidence and meteorological factors or school holidays, while limited studies focused on their association on transmissibility. We aimed to measure the transmissibility of HFMD and to examine its potential driving factors in Hong Kong. A likelihood-based procedure was used to estimate time-dependent effective reproduction number (R(t)) based on weekly number of HFMD-associated hospitalizations from 2010 to 2014. The associations of between-year effects, depletion of susceptibles, absolute humidity and school holidays with R(t) were examined using linear regression. R(t) usually started increasing between early spring and summer and peaked in April to May at around 1.1–1.2, followed by a slight rebound in autumn. Depletion of susceptibles and between-years effects explained most of the variances (19 and 13% respectively) in R(t). We found a negative association between depletion of susceptibles and R(t) (coefficients ranged from −0.14 to −0.03 for different years), but the estimated effects of absolute humidity and school holidays were insignificant. Overall, HFMD transmission was moderate in Hong Kong and was mainly associated with depletion of susceptibles. Limited impact was suggested from meteorological factors and school holidays.",2016 Jun 7,"['Yang, Bingyi', 'Lau, Eric H. Y.', 'Wu, Peng', 'Cowling, Benjamin J.']",Sci Rep,,,True
2acdee7df15edf13c1f992bc7aed50fa3a193ae6,PMC,"Transmission of Hand, Foot and Mouth Disease and Its Potential Driving Factors in Hong Kong",http://dx.doi.org/10.1038/srep27500,PMC4895171,27271966,CC BY,"Hand-foot-and-mouth disease (HFMD) is a common childhood disease with substantial disease burden in Asia. Mixed results were reported on the associations between HFMD incidence and meteorological factors or school holidays, while limited studies focused on their association on transmissibility. We aimed to measure the transmissibility of HFMD and to examine its potential driving factors in Hong Kong. A likelihood-based procedure was used to estimate time-dependent effective reproduction number (R(t)) based on weekly number of HFMD-associated hospitalizations from 2010 to 2014. The associations of between-year effects, depletion of susceptibles, absolute humidity and school holidays with R(t) were examined using linear regression. R(t) usually started increasing between early spring and summer and peaked in April to May at around 1.1–1.2, followed by a slight rebound in autumn. Depletion of susceptibles and between-years effects explained most of the variances (19 and 13% respectively) in R(t). We found a negative association between depletion of susceptibles and R(t) (coefficients ranged from −0.14 to −0.03 for different years), but the estimated effects of absolute humidity and school holidays were insignificant. Overall, HFMD transmission was moderate in Hong Kong and was mainly associated with depletion of susceptibles. Limited impact was suggested from meteorological factors and school holidays.",2016 Jun 7,"['Yang, Bingyi', 'Lau, Eric H. Y.', 'Wu, Peng', 'Cowling, Benjamin J.']",Sci Rep,,,True
f9e8af068e552f4327e0e7cdd359674967d9d422,PMC,Reducing burden of disease from residential indoor air exposures in Europe (HEALTHVENT project),http://dx.doi.org/10.1186/s12940-016-0101-8,PMC4895703,26961383,CC BY,"BACKGROUND: The annual burden of disease caused indoor air pollution, including polluted outdoor air used to ventilate indoor spaces, is estimated to correspond to a loss of over 2 million healthy life years in the European Union (EU). Based on measurements of the European Environment Agency (EEA), approximately 90 % of EU citizens live in areas where the World Health Organization (WHO) guidelines for air quality of particulate matter sized < 2.5 mm (PM(2.5)) are not met. Since sources of pollution reside in both indoor and outdoor air, selecting the most appropriate ventilation strategy is not a simple and straightforward task. METHODS: A framework for developing European health-based ventilation guidelines was created in 2010–2013 in the EU-funded HEALTHVENT project. As a part of the project, the potential efficiency of control policies to health effects caused by residential indoor exposures of fine particulate matter (PM(2.5)), outdoor bioaerosols, volatile organic compounds (VOC), carbon oxide (CO) radon and dampness was estimated. The analysis was based on scenario comparison, using an outdoor-indoor mass-balance model and varying the ventilation rates. Health effects were estimated with burden of diseases (BoD) calculations taking into account asthma, cardiovascular (CV) diseases, acute toxication, respiratory infections, lung cancer and chronic obstructive pulmonary disease (COPD). RESULTS: The quantitative comparison of three main policy approaches, (i) optimising ventilation rates only; (ii) filtration of outdoor air; and (iii) indoor source control, showed that all three approaches are able to provide substantial reductions in the health risks, varying from approximately 20 % to 44 %, corresponding to 400 000 and 900 000 saved healthy life years in EU-26. PM(2.5) caused majority of the health effects in all included countries, but the importance of the other pollutants varied by country. CONCLUSIONS: The present modelling shows, that combination of controlling the indoor air sources and selecting appropriate ventilation rate was the most effective to reduce health risks. If indoor sources cannot be removed or their emissions cannot be limited to an accepted level, ventilation needs to be increased to remove remaining pollutants. In these cases filtration of outdoor air may be needed to prevent increase of health risks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12940-016-0101-8) contains supplementary material, which is available to authorized users.",2016 Mar 8,"['Asikainen, Arja', 'Carrer, Paolo', 'Kephalopoulos, Stylianos', 'Fernandes, Eduardo de Oliveira', 'Wargocki, Pawel', 'Hänninen, Otto']",Environ Health,,,True
c5375b07f72048d739efc376420a5cb5374392d6,PMC,Reducing burden of disease from residential indoor air exposures in Europe (HEALTHVENT project),http://dx.doi.org/10.1186/s12940-016-0101-8,PMC4895703,26961383,CC BY,"BACKGROUND: The annual burden of disease caused indoor air pollution, including polluted outdoor air used to ventilate indoor spaces, is estimated to correspond to a loss of over 2 million healthy life years in the European Union (EU). Based on measurements of the European Environment Agency (EEA), approximately 90 % of EU citizens live in areas where the World Health Organization (WHO) guidelines for air quality of particulate matter sized < 2.5 mm (PM(2.5)) are not met. Since sources of pollution reside in both indoor and outdoor air, selecting the most appropriate ventilation strategy is not a simple and straightforward task. METHODS: A framework for developing European health-based ventilation guidelines was created in 2010–2013 in the EU-funded HEALTHVENT project. As a part of the project, the potential efficiency of control policies to health effects caused by residential indoor exposures of fine particulate matter (PM(2.5)), outdoor bioaerosols, volatile organic compounds (VOC), carbon oxide (CO) radon and dampness was estimated. The analysis was based on scenario comparison, using an outdoor-indoor mass-balance model and varying the ventilation rates. Health effects were estimated with burden of diseases (BoD) calculations taking into account asthma, cardiovascular (CV) diseases, acute toxication, respiratory infections, lung cancer and chronic obstructive pulmonary disease (COPD). RESULTS: The quantitative comparison of three main policy approaches, (i) optimising ventilation rates only; (ii) filtration of outdoor air; and (iii) indoor source control, showed that all three approaches are able to provide substantial reductions in the health risks, varying from approximately 20 % to 44 %, corresponding to 400 000 and 900 000 saved healthy life years in EU-26. PM(2.5) caused majority of the health effects in all included countries, but the importance of the other pollutants varied by country. CONCLUSIONS: The present modelling shows, that combination of controlling the indoor air sources and selecting appropriate ventilation rate was the most effective to reduce health risks. If indoor sources cannot be removed or their emissions cannot be limited to an accepted level, ventilation needs to be increased to remove remaining pollutants. In these cases filtration of outdoor air may be needed to prevent increase of health risks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12940-016-0101-8) contains supplementary material, which is available to authorized users.",2016 Mar 8,"['Asikainen, Arja', 'Carrer, Paolo', 'Kephalopoulos, Stylianos', 'Fernandes, Eduardo de Oliveira', 'Wargocki, Pawel', 'Hänninen, Otto']",Environ Health,,,True
d3faa41624a8a99e5f600923cbe61fc457fb76a6,PMC,Nonstructural protein 11 (nsp11) of porcine reproductive and respiratory syndrome virus (PRRSV) promotes PRRSV infection in MARC-145 cells,http://dx.doi.org/10.1186/s12917-016-0717-5,PMC4895886,27268206,CC BY,"BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) induces one of most important devastating disease of swine worldwide, and the current methods poorly control it. Previous studies have indicated that the nonstructural protein 11 (nsp11) of PRRSV may be an important protein for the immune escape of PRRSV. RESULTS: Here, we firstly explored the effect of over-expression of nsp11 on PRRSV infection and found that over-expression of nsp11 enhanced the PRRSV titers while the small interfering RNA (siRNAs) specifically targeting nsp11 could reduce the PRRSV titers in MARC-145 cells. CONCLUSION: In conclusion, PRRSV nsp11 promotes PRRSV infection in MARC-145 cells and siRNAs targeting nsp11 may be a potential therapeutic strategy to control PRRSV in future.",2016 Jun 6,"['Shi, Xibao', 'Zhang, Xiaozhuan', 'Chang, Yongzhe', 'Jiang, Bo', 'Deng, Ruiguang', 'Wang, Aiping', 'Zhang, Gaiping']",BMC Vet Res,,,True
962c3880e4fee95b974d6d754a568278cc72e6d7,PMC,Medicinal plants – prophylactic and therapeutic options for gastrointestinal and respiratory diseases in calves and piglets? A systematic review,http://dx.doi.org/10.1186/s12917-016-0714-8,PMC4896019,27268043,CC BY,"BACKGROUND: Gastrointestinal and respiratory diseases in calves and piglets lead to significant economic losses in livestock husbandry. A high morbidity has been reported for diarrhea (calves ≤ 35 %; piglets ≤ 50 %) and for respiratory diseases (calves ≤ 80 %; piglets ≤ 40 %). Despite a highly diverse etiology and pathophysiology of these diseases, treatment with antimicrobials is often the first-line therapy. Multi-antimicrobial resistance in pathogens results in international accordance to strengthen the research in novel treatment options. Medicinal plants bear a potential as alternative or additional treatment. Based on the versatile effects of their plant specific multi-component-compositions, medicinal plants can potentially act as ‘multi-target drugs’. Regarding the plurality of medicinal plants, the aim of this systematic review was to identify potential medicinal plant species for prevention and treatment of gastrointestinal and respiratory diseases and for modulation of the immune system and inflammation in calves and piglets. RESULTS: Based on nine initial sources including standard textbooks and European ethnoveterinary studies, a total of 223 medicinal plant species related to the treatment of gastrointestinal and respiratory diseases was identified. A defined search strategy was established using the PRISMA statement to evaluate 30 medicinal plant species starting from 20’000 peer-reviewed articles published in the last 20 years (1994–2014). This strategy led to 418 references (257 in vitro, 84 in vivo and 77 clinical trials, thereof 48 clinical trials in veterinary medicine) to evaluate effects of medicinal plants and their efficacy in detail. The findings indicate that the most promising candidates for gastrointestinal diseases are Allium sativum L., Mentha x piperita L. and Salvia officinalis L.; for diseases of the respiratory tract Echinacea purpurea (L.) MOENCH, Thymus vulgaris L. and Althea officinalis L. were found most promising, and Echinacea purpurea (L.) MOENCH, Camellia sinensis (L.) KUNTZE, Glycyrrhiza glabra L. and Origanum vulgare L. were identified as best candidates for modulation of the immune system and inflammation. CONCLUSIONS: Several medicinal plants bear a potential for novel treatment strategies for young livestock. There is a need for further research focused on gastrointestinal and respiratory diseases in calves and piglets, and the findings of this review provide a basis on plant selection for future studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0714-8) contains supplementary material, which is available to authorized users.",2016 Jun 6,"['Ayrle, Hannah', 'Mevissen, Meike', 'Kaske, Martin', 'Nathues, Heiko', 'Gruetzner, Niels', 'Melzig, Matthias', 'Walkenhorst, Michael']",BMC Vet Res,,,True
023858d3191988a37587ab951db561a3db3ae2cd,PMC,Evaluation of custom multiplex real - time RT - PCR in comparison to fast - track diagnostics respiratory 21 pathogens kit for detection of multiple respiratory viruses,http://dx.doi.org/10.1186/s12985-016-0549-8,PMC4896093,27267595,CC BY,"BACKGROUND: Severe acute respiratory infections in children can be fatal, rapid identification of the causative agent and timely treatment can be life saving. Multiplex real time RT-PCR helps in simultaneous detection of multiple viruses saving cost, time and labour. Commercially available multiplex real time RT-PCR kits are very expensive. Therefore the aim of the present study was to develop a cost effective multiplex real time RT-PCR for the detection of 18 respiratory viruses and compare it with an in-vitro diagnostics approved Fast Track Diagnostic Respiratory Pathogens 21 Kit (FTD). METHODS: Nasopharyngeal aspirates and throat swabs were collected and processed for extraction of nucleic acid using an automated extraction system and multiplex real time RT-PCR was performed using the FTD kit and a custom assay on 356 samples. RESULTS: Custom and FTD assays detected one or more respiratory viruses in 268 (75.29 %) and 262 (73.60 %) samples respectively. The concordance between the custom assay and the FTD assay was 100 % for HCoV OC43, HCoV 229E, HPIV-1, HPIV-2, HBoV, HPeV, Flu A, and Influenza A(H1N1)pdm09 and 94.66 – 99.71 % for the remaining viruses; Flu B (99.71 %), HRV (99.71 %), HPIV-3 (98.87 %), HPIV-4 (99.43 %), HCoV NL63 (99.71 %), HMPV A/B (99.71 %), RSV A/B (94.66 %), EV (98.31 %), HCoV HKU1 (99.71 %), HAdV (99.71 %). Major discrepancy was observed for RSV A/B, which was over detected in 18 samples by the custom assay as compared to the FTD assay. The custom assay was much cheaper than the FTD assay and the time taken was only 29 min more. CONCLUSION: The custom primer and probe mix was found to be comparable to the FTD assay with good concordance but was much cheaper and the time taken for reporting was only 29 min more. The low cost custom multiplex RT-PCR can be a useful alternative to the costly FTD kit for rapid identification of viral aetiology in resource limited settings.",2016 Jun 6,"['Malhotra, Bharti', 'Swamy, M. Anjaneya', 'Reddy, P. V. Janardhan', 'Kumar, Neeraj', 'Tiwari, Jitendra Kumar']",Virol J,,,True
a5293bb4f17ad25a72133cdd9eee8748dd6a4b8d,PMC,"XXIV World Allergy Congress 2015: Seoul, Korea. 14-17 October 2015",http://dx.doi.org/10.1186/s40413-016-0096-1,PMC4896250,,CC BY,"A1 Pirfenidone inhibits TGF-b1-induced extracellular matrix production in nasal polyp-derived fibroblasts Jae-Min Shin, Heung-Man Lee, Il-Ho Park A2 The efficacy of a 2-week course of oral steroid in the treatment of chronic spontaneous urticaria refractory to antihistamines Hyun-Sun Yoon, Gyeong Yul Park A3 The altered distribution of follicular t helper cells may predict a more pronounced clinical course of primary sjögren’s syndrome Margit Zeher A4 Betamethasone suppresses Th2 cell development induced by langerhans cell like dendritic cells Katsuhiko Matsui, Saki Tamai, Reiko Ikeda A5 An evaluation of variousallergens in cases of allergic bronchial asthma at lucknow and neighbouring districts by intradermal skintest Drsushil Suri, Dranu Suri A6 Evaluation ferqency of ADHD in childhood asthma Marzieh Heidarzadeh Arani A7 Steven johnson syndrome caused by typhoid fever in a child Azwin Lubis, Anang Endaryanto A8 Chronic Bronchitis with Radio Contrast Media Hypersensitivity: A Case with Hypothesized GINA Step 1 Asthma Shinichiro Koga A9 The association between asthma and depression in Korean adult : An analysis of the fifth korea national health and nutrition examination survey (2010-2012) Lee Ju Suk A10 Management of allergic disease exacerbations in pregnancy Yasunobu Tsuzuki A11 Subcutaneous immunotherapy mouse model for atopic dermatitis Seo Hyeong Kim, Jung U Shin, Ji Yeon Noh, Shan Jin, Shan Jin, Hemin Lee, Jungsoo Lee, Chang Ook Park, Kwang Hoon Lee, Kwang Hoon Lee A12 Atopic disease and/or atopy are risk factors for local anesthetic allergy in patients with history of hypersensitivity reactions to drugs? Fatma Merve Tepetam A13 Food hypersensitivity in patients with atopic dermatitis in Korea Chun Wook Park, Jee Hee Son, Soo Ick Cho, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Hye One Kim, Hee Jin Cho A14 Anaphylaxis caused by an ant (Brachyponera chinensis) in Japan Yoshinori Katada, Toshio Tanaka, Akihiko Nakabayashi, Koji Nishida, Kenichi Aoyagi, Yuki Tsukamoto, Kazushi Konma, Motoo Matsuura, Jung-Won Park, Yoshinori Harada, Kyoung Yong Jeong, Akiko Yura, Maiko Yoshimura A15 Anti-allergic effect of anti-IL-33 by suppression of immunoglobulin light chain and inducible nitric oxide synthase Tae-Suk Kyung, Young Hyo Kim, Chang-Shin Park, Tae Young Jang, Min-Jeong Heo, Ah-Yeoun Jung, Seung-Chan Yang A16 Food hypersensitivity in patients with chronic urticaria in Korea Hye One Kim, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Jee Hee Son, Chun Wook Park, Hee Jin Cho A17 Dose optimizing study of a depigmented polymerized allergen extract of phleum pollen by means of conjunctival provocation test (CPT) Angelika Sager, Oliver Pfaar A18 Correlation of cutaneous sensitivity and cytokine response in children with asthma Amit Agarwal, Meenu Singh, Bishnupda Chatterjee, Anil Chauhan A19 Colabomycin E, a Streptomycete-Derived Secondary Metabolite, Inhibits Proinflammatory Cytokines in Human Monocytes/Macrophages Ilja Striz, Eva Cecrdlova, Katerina Petrickova, Libor Kolesar, Alena Sekerkova, Veronika Svachova, Miroslav Petricek A20 Intravenous immunoglobluin treatment in a child with resistant atopic dermatitis: A brief review on this therapeutic regimen Hyuck Hoon Kwon, Kyu Han Kim A21 Wheat allergy is difficult to diagnose then other food allergens Suman Kumar A22 The effects of spirulina (Arthrospira platensis) dietary supplement as an adjunct therapy for children aged 7 to 14 years old with asthma: A randomized - double blind placebo controlled clinical trial Lou Ver Leigh Arciaga Manzon, Pilar Agnes Gonzalez Andaya A23 The study about cause and clinicopathological findings of injection induced dermatitis Bark-Lynn Lew, Youngjun Oh, Dongwoo Suh, Woo-Young Sim A24 IgE reactivity of recombinant allergen pac c 3 of the Asian needle ant pachycondyla chinensis Kyoung Yong Jeong, Myung-Hee Yi, Mina Son, Dongpyo Lyu, Jae-Hyun Lee, Tai-Soon Yong, Chein-Soo Hong, Jung-Won Park A25 Characterization of specific IgE antibody related to antigen 5 of echinococcus granulosus Mohammadreza Siavashi A26 Development of binary forecast model of asthma exacerbation: Asthma index Hey Suk Yun, Ha-Na Kang, Jae-Won Oh, Young Jin Choi A27 Different levels in rantes, IL-5 and TNF-á between the nasal polyps of adolescents with allergic, local allergic and non-allergic rhinitis Ha-Na Kang, Jae-Won Oh, Young Jin Choi A28 Tgfβ1 level is associated with VDR gene polymorphism in children with allergy diseases Tatiana Sentsova, Ilya Vorozhko, Olga Chernyak, Vera Revyakina, Anna Timopheeva, Andrey Donnikov A29 Dynamics of immunological biomarkers in children with food allergy fed goat milk formula Tatiana Sentsova, Ilya Vorozhko, Olga Chernyak, Vera Revyakina, Anna Timopheeva A30 Association between obesity, abdominal obesity and adiposity and the prevalence of atopic dermatitis in young Korean adults: The korea national health and nutrition examination survey, 2008–2010 Ji Hyun Lee, Young Min Park, Sang Soo Choi, Kyung Do Han, Han Mi Jung, Young Hoon Youn, Jun Young Lee, Yong Gyu Park, Seung-Hwan Lee A31 Associations of natural history and environmental factors with asthma among children in rural and urban areas of guangdong, China Zhaowei Yang, Jing Li, Mulin Feng, Marjut Roponen, Bianca Schaub, Gary WK Wong A32 The effect of CO2-enriched atmospheres to producing of allergenic pollen by ragweed Young Jin Choi, Ha-Na Kang, Jae-Won Oh A33 Application evaluation of house dust mite and components specific-IgE and IgG4 in specific immunotherapy with allergic diseases Baoqing Sun, Peiyan Zheng A34 Effect of Asian dust events on asthma according to the socioeconomic status using claim data in KOREA Yoon-Sung Park A35 TSLP downregulates human â-defensin 2 through STAT3-dependent pathway in keratinocytes Sang Wook Son A36 Effects of anti-IgE on IL-4, IL-5, IL-17, and CD19,20,200 in a case of netherton syndrome (SPINK5 mutation) Arzu Didem Yalcin, Sukran Kose, Kemal Kiraz A37 Augmentation of arginase 1 expression exacerbates airway inflammation in murine asthma models Jin-Young Lee, Sehyo Yune, Jae-Won Paeng, Mi-Jung Oh, Byung-Jae Lee, Dong-Chull Choi, Young Hee Lim, Kyoung Won Ha A38 Caregivers of children with no food allergy – their experiences and perception of the condition Kiwako Yamamoto-Hanada, Masami Narita, Masaki Futamura, Yukihiro Ohya A39 Evaluation of Drug Provocation Tests in Korean Children: A Single Center Experience Jihyun Kim, Jinwha Choi, Kwanghoon Kim, Jaehee Choi, Kangmo Ahn A40 Danyoung classification 2015 update by digital HD endoscopic evaluation SUN-HO/Brian Chang A41 Effect on quality of life of the mixed house dust mite/weed pollen extract immunotherapy in polysensitized patients Lisha Li A42 Ambient desert dust and allergic symptoms: A time series analysis from a national birth cohort (JECS) Kumiko Tsuji Kanatani, Yu-Ichi Adachi A43 Individuals Allergic to Cow’s Milk Should be Vigilant When Consuming Beef Because It May be Injected Beef Shigeyuki Narabayashi, Ikuo Okafuji, Yuya Tanaka, Satoru Tsuruta, Nobue Takamatsu A44 Quality of life of chronic rhinosinusitis patients with or without nasal polyps in Korea Soo Whan Kim, Do Hyun Kim A45 House dust mite sensitization and exacerbation of asthma in the fall in children Jong-Seo Yoon, Jin Tack Kim, Hwan Soo Kim, Yoon Hong Chun, Hyun Hee Kim, Sul Mui Won A46 Evidence-based health advice for childhood eczema and household pets Kam Lun E. Hon, Chung Mo Chow, Ting Fan Leung A47 Relationship between allergic rhinitis and mental health in korea Do Hyun Kim, Soo Whan Kim A48 Oscillometric bronchodilator response in 3 to 5 years old healthy and asthmatic Filipino children Gemmalyn Esguerra, Emily Resurreccion, Kristine Elisa Kionisala, Jenni Rose Dela Cruz A49 The use of aeroallergen immunotherapy to treat eosinophilic esophagitis Muhammad Imran A50 A study of the eczema herpeticum in Korean Yun Seon Choe, Kyu Han Kim, Mira Choi A51 Specific sublingual immunotherapy in Korean patients with atopic dermatitis Byung Soo Kim, Hyun-Joo Lee, Jeong-Min Kim, Jeong-Min Kim, Gun-Wook Kim, Je-Ho Mun, Je-Ho Mun, Hoon-Soo Kim, Margaret Song, Hyun-Chang Ko, Hyun-Chang Ko, Moon-Bum Kim A52 Association between polymorphisms in bitter taste receptors genes and clinical features in Korean asthmatics Sun-Young Yoon A53 Effect of glycosides based standardized fenugreek seed extract in bleomycin-induced pulmonary fibrosis in rats Amit Kandhare A54 A kampo formula, ogi-kenchu-to, decreases side-effects of steroid ointment for infantile atopic dermatitis: Three cases report Noriko Yahiro A55 To test use of jet nebulizers NE-C802 as a drug delivery system in the children with asthma Amit Agarwal, Meenu Singh, Jasleen Kaur, Ruby Pawankar, Pankaj Pant, Sukhmanjeet Singh A56 Immunoglobulin e to allergen components of house dust mite in Korean children with allergic disease Hwan Soo Kim, Jong-Seo Yoon, Sul Mui Won, Yoon Hong Chun, Jin Tack Kim, Hyun Hee Kim A57 Effectiveness of premedication and rapid desensitization in hypersensitivity to l-asparaginase Hwan Soo Kim, Sul Mui Won, Yoon Hong Chun, Jong-Seo Yoon, Hyun Hee Kim, Jin Tack Kim A58 Angioedema with Eosinophilia: The First Report from Thailand Thatchai Kampitak A59 Evaluation of anti-pruritic and anti-inflammatory effects of Korean red ginseng extract on atopic dermatitis murine model So Min Kim, Hyun Joo Lee, Hei Sung Kim, Jeong Deuk Lee, Sang Hyun Cho A60 Subcutaneous autologous serum therapy in chronic urticaria Kiran Godse A61 Allergic bronchopulmonary aspergillosis in asthma and lung tuberculosis Juwita Soekarno, Sarie Ratnasari, E. Alwi Datau, Eko Surachmanto, JC Matheos A62 Infantile eczema is associated with campylobacter and roseburia subpopulations but not microbial diversity in stool samples of Chinese newborns Ting Fan Leung, Jamie Sui-Lam Kwok, Christine Kit-Ching Tung, Man Fung Tang, Stephen Kwok-Wing Tsui, Gary WK Wong, Kam Lun Ellis Hon, Wing Hung Tam, Hing Yee Sy A63 Association between serum chitinase level and toll-like receptor polymorphisms in bakery workers Sohee Lee A64 IFN-gamma contributes to nasal polypogenesis by inducing epithelial-to-mesenchymal transition via non-smad pathway Hyun-Woo Shin, Mingyu Lee, Dae Woo Kim, Roza Khalmuratova A65 Management and education status of anaphylaxis patients who visit our emergency room (ER) Mi Yeoung Kim, Jaewon Jeong, Chansun Park A66 Hypoallergen-Encoding DNA Plasmids As Immunoprophylactic Vaccines of Shrimp Tropomyosin Hypersensitivity Christine Yee Yan Wai, Patrick S.C. Leung, Nicki Y.H. Leung, Ka Hou Chu A67 The relationship between sputum pentraxin 3 levels and childhood asthma Hee Seon Lee, Kyung Eun Lee, Jung Yeon Hong, Mi Na Kim, Min Jung Kim, Yoon Hee Kim, In Suk Sol, Seo Hee Yoon, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim A68 The role of local antibody responses in the nasal inflammation of allergic rhinitis (AR) patients Ji Hye Kim, Hae-Sim Park, Yoo Seob Shin, Young Min Ye, Daehong Seo, Moon Gyeong Yoon, Young Mok Lee A69 A case of ofloxacin-induced anaphylaxis by non-IgE, but specific IgG4-mediated responses Daehong Seo, Ji Hye Kim, Young-Mok Lee, Young Min Ye, Hae-Sim Park A70 Serum LTE4 metabolite as a biomarker for aspirin exacerbated respiratory disease Ga Young Ban, Kumsun Cho, Seung-Hyun Kim, Yong Eun Kwon, Moon Gyeong Yoon, Ji Hye Kim, Yoo Seob Shin, Young Min Ye, Dong-Ho Nahm, Hae-Sim Park A71 Local and systemic reactions of dust mite subcutaneous immunotherapy (SCIT) among children in a tertiary care hospital Pilar Agnes Gonzalez Andaya A72 Effects of carboxymethyl glucan (CM-glucan) in children with allergic rhinitis and asthma: A randomized controlled trial Pilar Agnes Gonzalez Andaya A73 Autophagy mechanisms in patients with severe asthma: A new therapeutic target Ga Young Ban, Chang Gyu Jung, Seung-Ihm Lee, Duy Le Pham, Dong-Hyeon Suh, Eun-Mi Yang, Young Min Ye, Yoo Seob Shin, Hae-Sim Park A74 Aggravation of airway inflammation and hypperresponsiveness following nasal challenge with dermatophagoides pteronyssinus in perennial allergic rhinitis patients without symptoms of asthma Wan Jun Wang, MO Xian, Yan Qing Xie, Jing Ping Zheng, Jing Li A75 Serum 25-hydroxyvitamin d in early childhood is non-linearly associated with allergy Emma Merike Savilahti, Outi Mäkitie, Anna Kaarina Kukkonen, Sture Andersson, Heli Viljakainen, Erkki Savilahti, Mikael Kuitunen A76 Fric test in dermographism Kiran Godse A77 Neutrophil autophagy and extracellular trap could contribute to asthma severity Duy Le Pham, Ga Young Ban, Seung-Hyun Kim, Eun-Mi Yang, Hae-Sim Park, Ji-Ho Lee, Yong-Joon Chwae A78 Redox Modulation for the Treatment of Toluene Diisocyanates-Induced Lung Inflammation Li-Ming Chin, Chi-Chang Shieh A79 A case of occupational asthma and rhinitis with anaphylaxis to Korean ginseng and sanyak Ji Hye Kim, Hye-Soo Yoo, Moon Gyeong Yoon, Ga Young Ban, Ga Young Ban, Yoo Seob Shin, Young Min Ye, Hae-Sim Park A80 Factors of influencing epidermal permeability barrier defects in atopic dermatitis children Myong Soon Sung, Jin Uck Choi, Sung Won Kim, Yong Jin Hwang A81 Innate type 2 response to aspergillusfumigatus in a murine model of atopic dermatitis-like skin inflammation Arum Park, Eun Lee, Song-I Yang, Hyun-Ju Cho, Jinho Yu A82 Activin a receptor 1C may implicate in the development of sensitive skin Dong Hun Lee, Eun Ju Kim, Yeon Kyung Kim, Eun Jin Doh, Hee Chul Eun, Jin Ho Chung, Young Mee Lee, Seon Pil Jin A83 Genetic association and eQTL analyses of genes associated with allergy in atopic/non-atopic asthma Xingnan Li, Naftali Kaminski, Sally Wenzel, Eugene Bleecker, Deborah Meyers A84 Gastroscope feature and clinical characteristics in 172 cases of children with henoch-schonlein purpura Zeng Huasong A85 The role of TRPV1 in CD4+ t cell mediated inflammatory response of allergic rhinitis Ji-Hun Mo, Ramachandran Samivel, Eun-Hee Kim, Ji-Hye Kim, Jun-Sang Bae, Young-Jun Chung, Dae Woo Kim A86 A Phenotype of Rhinitis from School Children Is Associated with the Development of Bronchial Hyperresponsiveness Eun Lee, Si Hyeon Lee, Young-Ho Kim, Hyun-Ju Cho, Ho-Sung Yu, Mi-Jin Kang, Song-I Yang, Young-Ho Jung, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, So-Yeon Lee, Ho-Jang Kwon, Soo-Jong Hong A87 Increased basal activation status was noted in adult anaphylaxis patients Sailesh Palikhe, Hae-Sim Park, Seung-Hyun Kim, Ji Hye Kim, Eun-Mi Yang A88 Clinical values of interferon-gamma enzyme-linked immunospot assays for management of antibiotic hypersensitivity in hospitalized patients Suda Sibunruang, Jettanong Klaewsongkram A89 VDR gene polymorphism and 25-hydroxy vitamin d levels in children with food allergy Tatiana Sentsova, Ilya Vorozhko, Anna Timopheeva, Olga Chernyak, Vera Revyakina, Andrey Sokolnikov A90 An analysis of 145 oral almond challenge tests Makoto Nisihino, Yu Okada, Noriyuki Yanagida, Motohiro Ebisawa, Sakura Sato, Kiyotake Ogura, Tomoyuki Asaumi, Kenichi Nagakura, Tetsuharu Manabe, Hirotoshi Unno A91 Effect of creatine supplementation in fish allergenic potential; A proteomics study Pedro M Rodrigues, Denise Schrama, Gadija Mohamed, Lizex Hüsselmann, Lizex Hüsselmann, Bongani Ndimba A92 Flagellin modulates the function of invariant NKT cells via dendritic cells in asthma patients Jae-Uoong Shim, Young Il Koh, Joon Haeng Rhee, Ji-Ung Jeong A93 Clinical and subclinical manifestations of allopurinol – induced severe cutaneous adverse reactions in Vietnam Dinh Van Nguyen, Hieu Chi Chu, Mui Thi Tran, Christopher Vidal, Suran Fernando, Sheryl Van Nunen, Sy Van Than A94 Time course of serum inhibitory activity for facilitated allergen-IgE binding during house dust mite immunotherapy Mulin Feng, Jing Li A95 Periostin is a novel biomarker in eosinophilic nasal polyps of chronic rhinosinusitis Dong-Kyu Kim, Seung-No Hong, Kyoung Mi Eun, Hong Ryul Jin, Dae Woo Kim A96 Dominance of Th1-response in children with refractory mycoplasma pneumoniae pneumonia Jun Bao, Yi-Xiao Bao A97 Studies on the role of CD14 polymorphism among pollen and mold induced asthmatics of kolkata, India Sanjoy Podder, Goutam Kumar, Shampa Dutta, Amlan Ghosh A98 House dust mite allergy – Indian perspective Goutam Kumar Saha, Sanjoy Podder, Salil Kumar Gupta A99 Increased expression of purinergic (P2Y12) receptor and cysteinyl leukotriene receptors in the lung tissue of a mouse model of allergic asthma Tu/Hoang Kim Trinh, Yoo Seob Shin, Hae-Sim Park, Jing-Nan Liu, Duy Le Pham A100 Autologous serum skin test in chronic idiopathic urticaria - relationship with autoimmune markers and disease severity Hyun-Chang Ko, Byung Soo Kim, Moon-Bum Kim A101 Anxiety and depression levels in severe asthma patients treated with omalizumab Ömer Özbudak, Fatih Üzer A102 Economic burden of refractory chronic spontaneous urticaria on Kuwait health system Mona Al-Ahmad, Maryam Alowayesh, Norman Carroll A103 IgE-mediated maize allergy in India: A 28 kd protein responsible for food-induced allergic reaction Anand Bahadur Singh A104 Liposomal encapsulation of house dust mite allergens and dexamethasone modulates allergic response in a murine model of asthma Yordanis Pérez-Llano, María Del Carmen Luzardo Lorenzo, Wendy Ramírez González, Carlos Calcines Cruz, Rady Laborde Quintana, Alain Morejón, Virgilio Bourg, Marilé Hechavarría Stoker A105 Immune Suppressive Effects of Tonsil-Derived Mesenchymal Stem Cells for Eosinophilic Rhinosinusitis with Nasal Polyps in a Mouse Model Jun-Sang Bae, Ramachandran Samivel, Eun-Hee Kim, Ji-Hye Kim, Ji-Hun Mo A106 Second line treatments of dermographic urticaria refractory to antihistamines Keiko Hanaoka, Michihiro Hide, Akio Tanaka, Makiko Hiragun, Mikio Kawai A107 Diagnostic Value of Specific IgE to Peanut and Ara h 2 in Korean Children with Peanut Allergy Kwanghoon Kim, Kwanghoon Kim, Hye-Young Kim, Jihyun Kim, Kangmo Ahn, Youngshin Han A108 Inappropriate amounts of topical tacrolimus applied on Korean patients with eczema Gun-Wook Kim, Hyun-Chang Ko, Byung Soo Kim, Moon-Bum Kim, Margaret Song A109 Identification of an IgG1-mediated anaphylaxis marker and its application in evaluating the antigenicity of infant formulas Takeshi Matsubara, Hiroshi Iwamoto, Yuki Nakazato, Kazuyoshi Namba, Yasuhiro Takeda A110 Nitric oxide as a screening tool for evaluation of postoperative state of chronic rhinosinusitis Jae Hoon Lee, Woo Yong Bae A111 Comparison of different medical treatment options for crswnp: Doxycycline, methylprednisolone, mepolizumab, omalizumab Els De Schryver, Lien Calus, Philippe Gevaert, Thibaut Van Zele, Claus Bachert A112 Successful treatment of steroid resistant asthma model by blocking CD28 signal Akio Mori, Satoshi Kouyama, Miyako Yamaguchi, Yo Iijima, Akemi Abe-Ohtomo, Hiroaki Hayashi, Kentaroh Watai, Chihiro Mitsui, Chiyako Oshikata, Kiyoshi Sekiya, Takahiro Tsuburai, Mamoru Ohtomo, Yuma Fukutomi, Masami Taniguchi A113 Serum periostin levels was not associated with allergic rhinitis and allergic sensitization in Korean children Ju Wan Kang, Jeong Hong Kim, Jeong Hong Kim, Keun-Hwa Lee, Hye-Sook Lee, Seong-Chul Hong, Jaechun Lee A114 Roles of ADAM10 and ADAM17 in allergic rhinitis Ji Won Seo, Jae Hoon Lee, Woo Yong Bae A115 Mechanism of oral and topical polyprenol action in atopic dermatitis Ivans Sergejs Kuznecovs, Galina Kuznecova A116 Technical and clinical validation of a mobile chamber for allergen exposure tests Karl-Christian Bergmann, Torsten Zuberbier, Joseph Salame, Torsten Sehlinger, Georg Bölke A117 The association between serum lead level and total immunoglobulin e according to allergic sensitization Yoo Suk Kim, Jung Hyun Chang, Jeong Hong Kim, Ju Wan Kang A118 Clinical and laboratory characteristics of nasal obstruction dominant allergic sensitization Seung-No Hong, Doo Hee Han, Chae-Seo Rhee A119 Nasal provocation test is useful for the diagnoses of allergic, non- allergic, and local allergic rhinitis Young-Joo Ko, Young Hyo Kim, Dae-Young Kim, Tae Young Jang A120 Aspirin facilitates the intestinal absorption and oral sensitization of food allergens in rats Tomoharu Yokooji, Taiki Hirano, Hiroaki Matsuo A121 Gestational Secondhand Smoke Exposure Could Affect Maternal n-Glycosylation and Cause Filaggrin Loss in Children with Atopic Dermatitis Galina Kuznecova, Ivans Sergejs Kuznecovs A122 Allergen specific immunotherapy in the treatment of allergic rhinitis and asthma--a randomized prospective study from kashmir valley-north of India Roohi Rasool Wani, Shafia Alam Syed, Ghulam Hassan, Ayaz Gul, Saniya Nissar, Zaffar Amin Shah A123 Sleep disorders in latin-American children with asthma and/or allergic rhinitis and normal controls Marilyn Urrutia Pereira, Carmen Fernandez, Dirceu Sole, Herberto Jose Chong Neto, Veronica Acosta, Alfonso Mario Cepeda, Mirta Alvarez Castello, Claudia Almendarez, Jose Santos Lozano Saenz, Juan C. Sisul, Nelson Rosario Filho, Antonio Castillo, Marylin Valentin Rostan, Jennifer Avila, Hector Badellino, Maria Carolina Manotas, Raúl Lázaro Castro Almarales, Mayda González León A124 Association between respiratory symptoms and exhaled nitric oxide in Afghanistan Woo Kyung Kim, Hae-Sun Yoon A125 ATP, a danger signal, activates human eosinophils via P2 purinergic receptors Takehito Kobayashi, Tooru Noguchi, Tomoyuki Soma, Kazuyuki Nakagome, Hidetomo Nakamoto, Hirohito Kita, Makoto Nagata A126 Atopic dermatitis and sleep disorders in latin American children Marilyn Urrutia Pereira, Dirceu Sole, Herberto Jose Chong Neto, Alfonso Mario Cepeda, Raúl Lázaro Castro Almarales, Juan C. Sisul, Marylin Valentin Rostan, Hector Badellino, Miguel Alejandro Medina Avalos, Antonio Castillo, Claudia Almendarez, Nelson Rosario Filho, Caridad Sanchez Silot, Jennifer Avila, Felicia Berroa Rodriguez, Jose Santos Lozano Saenz, Mirta Alvarez Castello, Carmen Fernandez A127 Der p 23: A Major House Dust Mite Allergen in Spite of Limited Release from Fecal Pellets and Prominent Protease Sensitivity Wai Tuck Soh, Alain Jacquet, Kiat Ruxrungtham, Emmanuel Nony, Maxime Le Mignon A128 Anaphylactic Reaction After Inhalation of Budesonide Mary Lee-Wong, Suzanne McClelland, Suzanne McClelland, Nanette B. Silverberg, Christian E. Song A129 Lipidomic analysis of mattress dust from urban and rural schoolchildren in China Zhaowei Yang, Jiukai Zhang, Wentao Zheng, Nanshan Zhong, Jing Li A130 Improvements in quality of life in children with allergic rhinitis after adenotonsillectomy Jung Ho Bae, Young Joo Cho, Joo Yeon Kim A131 The seasonal variation of asthma exacerbations in patients allergic to pollens in Greece Konstantinos Petalas, Dimitrios Vourdas, Christos Grigoreas A132 Whole-genome sequencing study in allergic rhinitis nuclear families Yuan Zhang A133 Effect of the production of extracellular matrix from nasal fibroblasts by eosinophils activated with airborne fungi Seung-Heon Shin, Mi-Kyung Ye, Jeong-Kyu Kim A134 The study of clinical characteristics, lung function and bronchodilator responsiveness in infants with RSV bronchiolitis Yong Feng, Yunxiao Shang A135 GIS-based association between PM10 and allergic diseases in seoul: Implication for health and environmental policy Sungchul Seo, Ji Tae Choung, Dohyeong Kim, Young Yoo, Hyunwook Lim A136 The relationship between rhinovirus and recurrent wheezing Wenjing Zhu, Chuanhe Liu, Li Sha, Li Chang, Min Zhao, Linqing Zhao, Yuan Qian, Yuzhi Chen A137 Dominancy of Staphylcoccus Aureus in the Skin of Atopic Dermatitis Patients Compared to Healthy Subjects through Metagenomic Analysis Min-Hye Kim, Young Joo Cho, Mina Rho, Jung-Won Kim, Yeon-Mi Kang, Kyung-Eun Yum, Hyeon-Il Choi, Jun-Pyo Choi, Han-Ki Park, Taek-Ki Min, Bok-Yang Pyun, Yoon-Keun Kim A138 Micronized Cellulose Powder Reduces the Dose of Locally Applied Glucocorticoids in Patients with Allergic Rhinitis Xueyan Wang A139 New strategy for atopic dermatitis therapy with modulation of calcium ion channels Woo Kyung Kim, Yu Ran Nam, Joo Hyun Nam A140 Difference in the Systemic Bacterial Composition of Atopic Dermatitis Patients Compared to Healthy Subjects through Metagenomic Analysis of Urine Jung-Won Kim, Min-Hye Kim, Mina Rho, Yeon-Mi Kang, Kyung-Eun Yum, Hyeon-Il Choi, Jun-Pyo Choi, Han-Ki Park, Taek-Ki Min, Young Joo Cho, Bok-Yang Pyun, Yoon-Keun Kim A141 Occurrence and physiological function of immune complexes of food proteins and IgA in human saliva Hiroshi Narita, Junko Hirose, Kumiko Kizu, Ayu Matsunaga A142 Association between DNA hypomethylation at IL13 gene and allergic rhinitis in house dust mite-sensitized subjects Jingyun Li, Yuan Zhang, Luo Zhang A143 Effect of dietary methyl donors on asthma and atopy is modified by MTHFR polymorphism Yean Jung Choi, Hye Lim Shin, Song-I Yang, So-Yeon Lee, Sung-Ok Kwon, Young-Ho Jung, Ji-Won Kwon, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, Se-Young Oh, Ho-Jang Kwon, Eun Lee, Mi-Jin Kang, Soo-Jong Hong, Yun-Jeong Lee, Joonil Kim A144 The effect of TSLP in a murine model of allergic asthma Joon Young Choi, Ji Young Kang, Seok Chan Kim, Sei Won Kim, Seung Joon Kim, Young Kyoon Kim, Chin Kook Rhee, Hea Yon Lee, Hwa Young Lee, Sook Young Lee A145 Evaluation of Aspirin Hypersensitivity in Chronic Rhinosinusitis Patients Tae Kyung Koh, Sung Wan Kim, Kun Hee Lee, Chul Kwon, Joong-Saeng Jo, Sung-Hwa Dong, Young Seok Byun A146 Chronic cough without wheezing in young children as a manifestation of chronic sinusitis Charles Song A147 Expression of muscarinic receptors and effect of tiotropium bromide on chronic asthma according to age in a murine model Ji Young Kang, Hwa Young Lee, In Kyoung Kim, Sei Won Kim, Chin Kook Rhee, Seung Joon Kim, Seok Chan Kim, Sook Young Lee, Young Kyoon Kim, Soon Seog Kwon, Joon Young Choi A148 Discrimination between non-eosinophilic and eosinophilic chronic rhinosinusitis with nasal polyps Pona Park, Hong Ryul Jin, Dong-Kyu Kim, Dae Woo Kim A149 Significant reduction in allergic features in the offspring of mice supplemented with specific non-digestible oligosaccharides during lactation Astrid Hogenkamp A150 Allergenicity assessment of hydrolysed infant formula; A multicenter comparison of a mouse model and a Guinea pig model for cow’s milk allergy Leon Knippels, Betty C.a.m. Van Esch, Jolanda Van Bilsen, Prescilla V. Jeurink; Marjan Gros, Johan Garssen, Joost J Smit, Raymond H.H. Pieters A151 Clinical significance between the allergic test and serum eosinophil cationic protein Boo-Young Kim, Soo Whan Kim A152 Hydroclorothiazide-induced acute non-cardiogenic pulmonary edema Ramon Lleonart A153 A Synbiotic Mixture of Scgos/Lcfos and Bifidobacterium Breve M-16V Is Able to Restore the Delayed Colonization of Bifidobacterium Observed in C-Section Delivered Infants Christophe Lay, Kaouther Benamor, Chua Mei Chen, Jan Knol, Charmaine Chew, Voranush Chongsrisawat, Anne Goh, Wen Chin Chiang, Rajeshwar Rao, Surasith Chaithongwongwatthana, Nipon Khemapech A154 Atopic characteristics of patients with asthma-COPD overlap syndrome Ji Young Yhi, Sang-Heon Kim, Dong Won Park, Ji-Yong Moon, Tae Hyung Kim, Jang Won Sohn, Dong Ho Shin, Ho Joo Yoon, Seok Hyun Cho A155 Perceptions and practices of severe asthma and asthma-COPD overlap syndrome among specialists: A questionnaire survey Sang-Heon Kim, Ji-Yong Moon, Jae-Hyun Lee, Ga Young Ban, Sujeong Kim, Mi-Ae Kim, Joo-Hee Kim, Min-Hye Kim, Chan-Sun Park, Hyouk-Soo Kwon, Jae-Woo Kwon, Jae Woo Jung, Hye-Ryun Kang, Jong-Sook Park, Tae-Bum Kim, Heung Woo Park, You Sook Cho, Kwang-Ha Yoo, Yeon-Mok Oh A156 A case of surgical diagnosed eosinophilic enteritis with intussusception in adult patient Sang-Rok Lee A157 Reference values of total IgE in estonian children Kaja Julge, Maire Vasar, Tiia Voor, Tiina Rebane A158 A case of eosinophilic granulomatosis with polyangiitis accompanied by rapidly progressive glomerulonephritis Yu Jin Kim, Sang Min Lee, Shin Myung Kang, Sojeong Kim, Sun Young Kyung, Sung Hwan Jeong, Jeong-Woong Park, Hyunjung Hwang, Yong Han Seon, Sanghui Park, Sang Pyo Lee A159 Associations Between Infectious Diseases and Urticaria Marius Iordache A160 Sleep in infants in korea – finding of bisq survey Yeongsang Jeong, Sohee Eun, Byung Min Choi, Ji Tae Choung, Wonhee Seo A161 Increased Expression of Filaggrin, TSLP, Periostin, IL13 and IL-33 in Nasal Polyps Liang Zhang, Ruby Pawankar, Manabu Nonaka, Miyuki Hayashi, Shingo Yamanishi, Harumi Suzaki, Yasuhiko Itoh, So Watanabe, Hitome Kobayashi A162 Asymptomatic bacteruria increases the risk of edematous attacks in patients with hereditary angioedema due to C1 inhibitor deficency (C1-INH-HAE) Zsuzsanna Zotter, Henriette Farkas, Lilian Varga, Nora Veszeli, Eva Imreh, Gabor Kovacs, Marsel Nallbani A163 Gastric Erosions Cause Spontaneous Urticaria Independent of Helicobacter Pylori Semen Zheleznov, Galina Urzhumtseva, Natalia Petrova, Zhanna Sarsaniia, Nikolai Didkovskii, Torsten Zuberbier A164 The Effect of G2 Vaccine on the Gene Expression NKG2D and Receptor Presenting on the Surface of NK Cells in Peripheral Blood Nader Dashti Gerdabi, Ali Khodadadi, Zahra Abdoli, Mehri Ghafourian, Mohammad Ali Assarehzadegan, Khodayar Ghorban A165 Ethnic differences in lifetime prevalence and indoor environmental factors for childhood eczema Hyo-Bin Kim, Hui Zhou, Jeong Hee Kim, Rima Habre, Theresa Bastain, Frank Gilliland A166 A case of methazolamide-induced toxic epidermal necrolysis Jong-Wook Bae, Kyu-Hyung Han, Young-Koo Jee, Misoo Choi, Seung-Phil Hong, Seung-Hyun Kim A167 Inflammatory responses of human adipose-tissue derived stem cells to LPS and nanoparticles Hee-Kyoo Kim, Gil-Soon Choi, Jeonghoon Heo, Young-Ho Kim, Eun-Kee Park A168 Analysis of 71 Cashew Nut Oral Challenge Tests Takashi Inoue, Kiyotake Ogura, Noriyuki Yanagida, Hirotoshi Unno, Kenichi Nagakura, Tetsuharu Manabe, Tomoyuki Asaumi, Sakura Sato, Yu Okada, Motohiro Ebisawa A169 Fungal sensitization is associated with asthma exacerbation Min-Gu Kim, You Sook Cho, Tae-Bum Kim, Hee-Bom Moon, Jung-Hyun Kim, Hyo-Jung Kim, So-Young Park, Bomi Seo, Hyouk-Soo Kwon, Jaemoon Lee, Taehoon Lee A170 Individual therapeutic patient education and consultation in children with atopic dermatitis Hye-Soo Yoo, Jieun Kim, Inok Kim, Haejin Kim, Younhee Chang, Hae-Sim Park, Sooyoung Lee A171 Utility of Alpha-Lactalbumin Specific IgE Levels Using Immulite 2000 3gAllergy in Predicting Clinical Severity of Milk Allergy Kazuyo Kuzume, Munemitsu Koizumi, Koji Nishimura, Michiko Okamoto A172 Isoniazid/rifampicin-specific t-cell responses in patients with anti-tuberculosis –induced dress syndrome Seung-Hyun Kim, Young Min Ye, Gyu Young Hur, Hae-Sim Park, Sang-Heon Kim, Young-Koo Jee A173 Genetic biomarkers associated with aspirin-exacerbated respiratory disease (AERD) phenotype based on genome-wide association study Seung-Hyun Kim, Hyunna Choi, Young Min Ye, Hae-Sim Park A174 Assessment of ORAL drug provocation test in the diagnosis of NON-steroidal ANTI-inflammatory drugs hypersensitivity Bui VAN Khanh, Hieu Chi Chu, Nguyen Nhu Nguyet, Nguyen Hoang Phuong A175 Korean treatment guideline of atopic dermatitis Joo Young Roh, Hyun Jeong Kim, Jung Eun Kim, Bark-Lynn Lew, Kyung Ho Lee, Seung-Phil Hong, Yong Hyun Jang, Kui Young Park, Seong Jun Seo, Jung Min Bae, Eung Ho Choi, Ki Beom Suhr, Seung Chul Lee, Hyun-Chang Ko, Young Lip Park, Sang Wook Son, Young Jun Seo, Yang Won Lee, Sang Hyun Cho, Chun Wook Park A176 Systemic side reaction of subcutaneous immunotherapy(SCIT) for perennial allergic rhinitis Kun Hee Lee, Sung Wan Kim A177 Clinical baseline characteristics of Asian patients suffering from refractory chronic spontaneous urticaria (CSU) in three phase 3 omalizumab clinical trials Chia-Yu CHU, Derrick Aw, Young-Min Ye, Giovanni Bader, Fabrizio Dolfi, Nathalie Oliveira A178 A metagenomic approach through t-RFLP to the microbiome of asthma Jae Chol Choi, Jae Woo Jung, Hye-Ryun Kang, Kijeong Kim, Byoung Whui Choi A179 Clinical characteristics and ten-year trend of peripheral blood eosinophilia among health screening program recipients at a tertiary hospital of South Korea Jong Wook Shin, Jae Woo Jung, Jae Chol Choi, In Won Park, Byoung Whui Choi, Jae Yeol Kim A180 The prevalence of toxocariasis and diagnostic value of serologic tests in asymptomatic Korean adults Jin-Young Lee, Kyoung Won Ha, Yun-Jin Jeung, Sehyo Yune, Byung-Jae Lee, Dong-Chull Choi, Mi-Jung Oh, Young Hee Lim A181 Cutaneous Drug Hypersensitivity Reaction in Korean Children: An Analysis of KAERS Database on 2012-2013 Eui Jun Lee, Dongin Suh, Sung-Il Woo, Hwa Jin Cho, Eun Hee Chung, Soo Youn Chung A182 Comparison of clinical characteristics, quality of life and sleep in patients with allergic rhinitis when categorised as “sneezers and runners” and “blockers” Kamal Gera, Ashok Shah A183 Role of s-nitrosoglutathione reductase (GSNOR) in the murine strain differences of airway hyperresponsiveness Jin-Young Lee, Kyoung Won Ha, Mi-Jung Oh, Young Hee Lim, Sehyo Yune, Jae-Won Paeng, Mi-Jin Jang, Byung-Jae Lee, Dong-Chull Choi A184 Protection from airway bronchoconstriction by gsno Jin-Young Lee, Mi-Jin Jang, Jae-Won Paeng, Yun-Jin Jeung, Young Hee Lim, Mi-Jung Oh, Kyoung Won Ha, Byung-Jae Lee, Dong-Chull Choi, Sehyo Yune A185 Does EIA-targeted asthma treatment improve daily physical activity of children? Takahiro Ito A186 Wheezing as a clue to the diagnosis of cough variant asthma and nonasthmatic eosinophilic bronchitis Jihye Kim, Jin-Young Lee, Sehyo Yune, Byung-Jae Lee, Dong-Chull Choi, Mi-Jin Jang, Jae-Won Paeng, Young Eun Kim, Young Nam Kim, Yongseok Lee A187 Antagonism of microRNA-21 suppressed the airway inflammation in a mouse model of bronchial asthma Hwa Young Lee, Sook Young Lee, Soon Seog Kwon, Young Kyoon Kim, Chin Kook Rhee, Sei Won Kim, Hea Yon Lee, Joon Young Choi, In Kyoung Kim A188 Chlorhexidine anaphylaxis: A report of two cases Jose Antonio Navarro, Maria Ascension Aranzabal, Alejandro Joral, Susana Lizarza, Miguel Echenagusia, EVA Maria Lasa A189 Effects of Particulate Matter on Respiratory Allergic Diseases Considering Meteorological Factors in Busan, Korea Eun-Jung Jo, Sun-Mi Jang, Seung-Eon Song, Hae-Jung Na, Chang-Hoon Kim, Woo-Seop Lee, Hye-Kyung Park A190 Clinical characteristics of neutrophilic asthma Sachiko Miyauchi, Yoshitaka Uchida, Tomoyuki Soma, Susumu Yamazaki, Toru Noguchi, Takehito Kobayashi, Kazuyuki Nakagome, Makoto Nagata A191 Current Practice of Infants and Children with Acute Urticaria at a Single Wide Regional Emergency Medical Center Hea Lin Oh, Do Kyun Kim, Dongin Suh, Young Yull Koh A192 Discordance between sputum eosinophilia and exhaled nitric oxide Sehyo Yune, Jin-Young Lee, Byung-Jae Lee, Dong-Chull Choi, Jae-Won Paeng, Mi-Jin Jang, Jihye Kim, Young Nam Kim A193 Association between genetic polymorphisms of costimulatory molecules and antituberculosis drugs induced hepatitis Sang-Heon Kim, Sang-Hoon Kim, Jang Won Sohn, Ho Joo Yoon, Dong Ho Shin, Jae Hyung Lee, Byoung Hoon Lee, Youn-Seup Kim, Jae-Seuk Park, Young-Koo Jee A194 The prevalence of gastroesophageal reflux disease in chronic unexplained cough Sehyo Yune, Jin-Young Lee, Jae-Won Paeng, Mi-Jin Jang, Dong-Chull Choi, Byung-Jae Lee, Yongseok Lee, Young Eun Kim A195 Risk Factors of Allergic Rhinitis in Preschool Children and Clinical Utility of Feno Jisun Yoon A196 Relationship between serum 25-hydroxyvitamin d and asthma exacerbation severity in children Yong Feng, Li Zhang, Xuxu Cai A197 Usefulness of Specific IgE Antibody Levels to Wheat, Gluten and Ï-5 Gliadin for Wheat Allergy in Korean Children Jong-Seo Yoon, Kyunguk Jeong, Hye-Soo Yoo, Sooyoung Lee, Sooyoung Lee A198 Neutralization of stratum corneum accelerates the progress from atopic dermatitis to asthma-like lesion in flaky tail mice treated by house dust mite allergen Hae-Jin Lee, Noo Ri Lee, Bo-Kyung Kim, Minyoung Jung, Dong Hye Kim, Catharina S. Moniaga, Kenji Kabashima, Eung Ho Choi A199 Trends in oral food challenges in Japan: A six-year prospective study Noriyuki Yanagida, Sakura Sato, Chizuko Sugizaki, Motohiro Ebisawa A200 The Gut Microbiome in the Food Allergic Host Jamie Kiehm, Punita Ponda, Sherry Farzan, Jared Weiss, Claudia Elera, Catherine Destio, Cristina Sison, Annette Lee A201 Cord blood cytokines and maternal environmental exposure during pregnancy Soo Hyun Ri, Chang Hoon Lim A202 Rupatadine pharmacokinetics in Japanese healthy volunteers after single and repeated oral doses of 10, 20 and 40 mg Iñaki Izquierdo Pulido, Jorg Taubel, Georg Ferber, Eva Santamaria Masdeu A203 A safe and effective method to desensitize patients with wheat allergy Alireza Khayatzadeh, Masoud Movahedi, Motohiro Ebisawa, Mohammad Gharagozlou A204 RNA Binding Protein Hur Regulates CD4+ T Cell Differentiation and Is Required for Allergic Airway Inflammation and Normal IL-2 Homeostasis Ulus Atasoy, Patsharaporn Techasintana, Matt Gubin, Jacqueline Glascock, Suzanne Ridenhour, Joseph Magee A205 Time Trends in the Epidemiology of Recurrent Wheezing in Infants from South America Nelson Rosario Filho; Herberto Jose Chong Neto, Gustavo Falbo Wandalsen, Ana Caroline Dela Bianca, Carolina Aranda, Dirceu Sole, Javier Mallol, Luis Garcia-Marcos, Luis Garcia-Marcos A206 Successful Cyclophosphamide Desensitization in a Pediatric Patient with Systemic Lupus Erythematosus Jennifer Toh, Yoomie Lee, Joyce Huang, Elina Jerschow, Jenny Shliozberg A207 The Fatty Acid Binding Protein Der p 13 Is a Minor House Dust Mite Allergen Able to Activate Innate Immunity Pattraporn Satitsuksanoa, Narissara Suratannon, Jongkonnee Wongpiyabovorn, Pantipa Chatchatee, Kiat Ruxrungtham, Alain Jacquet A208 Epidemiology of Stevens-Johnson Syndrome and Toxic Epidemal Necrolysis: An Administrative Database Study Min Suk Yang; Jin Yong Lee, Ja Yeun Kim, Han-Ki Park, Ju-Young Kim, Woo-Jung Song, Hye-Ryun Kang, Heung Woo Park, Yoon-Seok Chang, Sang-Heon Cho, Kyung-up Min, Chang-Han Park, Suk-Il Chang, Sook-Hee Song A209 Regional Differences of Vitamin D and Food-Induced Anaphylaxis in Korea Si-Heon Kim, Gil-Soon Choi, Su-Chin Kim, Ji Hye Kim, Ga Young Ban, Yoo Seob Shin, Hae-Sim Park, Young Min Ye A210 Triggering Factors of Atopic Dermatitis By Severity Yoon Ha Hwang A211 Clinical Features of Adverse Drug Reactions of Monoclonal Antibodies in Korea Da Woon Sim, Kyung Hee Park, Kyung Hee Park, Hye Jung Park, Hye Jung Park, Jung-Won Park, Jung-Won Park, Jae-Hyun Lee, Jae-Hyun Lee A212 Food Allergy with Eczema Is Associated with Reduced Growth in the First Four Years of Life Katrina Allen, Cara Beck, Jennifer Koplin, Melanie Matheson, Mimi Tang, Anne-Louise Ponsonby, Lyle Gurrin, Shyamali Dharmage, Melissa Wake, Vicki Mcwilliam A213 The Preliminary Study on Clinical Efficacy and Impact Factors of One Year’s Dust Mite Specific Immunotherapy in Allergic Asthma and Rhinitis Children Sensitized to Dust Mite Xiaoying Liu, Jing Wang, Li Xiang, Qun Wang A214 Lipopolysaccharide Signaling through Toll- like Receptor 4 Could be Augmented By Dermatophagoides Farinae in the Human Middle Ear Epithelial Cell Ji-Eun Lee, Dong-Young Kim, Chae-Seo Rhee, Chae-Seo Rhee A215 Drug Allergy in Pregnant Adolescents: Relation with Familial and Personal Atopy, and Substances Use Francisco Vazquez-Nava A216 Patients and Physicians Concept of Well-Controlled Asthma: Findings from Realise Asia Sang-Heon Cho, Jaewon Jeong, Diahn-Warng Perng, David Price, Glenn Neira, Jiangtao Lin A217 The Role of Vasoactive Intestinal Peptide in the Pathophysiology of Acute Asthma Olga Semernik A218 Comparison of Serum Cytokine Levels According to the Severity in Atopic Dermatitis Ha-Su Kim, Jin-a Jung, Ji-in Jung A219 The Different Influence on the Regulatory T Cell Response Between Subcutanous Immnuotherapy(SCIT) and Sublingual Immunotherapy(SLIT) in Children with Asthma Qing Miao, Li Xiang A220 Asthma State of Affairs in Asia: Seeing through Physicians’ and Patients’ Lenses Sang-Heon Cho, Jaewon Jeong, Diahn-Warng Perng, Jiangtao Lin, David Price A221 Identification of Aspirin Exacerbated Respiratory Disease (AERD) Phenotypes Using Two Step Cluster Analysis Hyun Young Lee, Hae-Sim Park, Young Min Ye, Su Chin Kim A222 Dusty Air Pollution Are Associated with an Increase Risk of Allergic Diseases in General Population Shokrollah Farrokhi, Mohammadkazem Gheiby A223 A Genome-Wide Association Study of Antituberculosis Drugs-Induced Hepatitis Sang-Heon Kim; Heung Woo Park, Sang-Hoon Kim, Young-Koo Jee A224 The Role of peroxiredoxin6 of Bronchial Epithelial Cells in Regulating Mitochondrial Function Under Oxidative Stress By Translocation to Outside Mitochondrial Membrane Sunjoo Park, Keun Ai Moon, Hyouk-Soo Kwon, Tae-Bum Kim, You Sook Cho, Hee-Bom Moon, Kyoung Young Lee, Gyong Hwa Hong, Eun Hee Ha A225 Toxic and Adjuvant Effects of 3 Types of Silica Nanoparticles on Airway System Heejae Han, Hye Jung Park, Yoon Hee Park, Yoon-Jo Kim, Kangtaek Lee, Jung-Won Park, Jae-Hyun Lee A226 Procedure for Diagnostic and Selection of Immunotherapy Method for Children with Different Immunopathogenetic Phenotypes of Atopic Dermatitis Tatiana Slavyanskaya, Vladislava Derkach A227 Prediction of the Success of Our Desensitization Protocol with Symptoms and Results of a Skin Prick Test in Patients with Hypersensitivity to Platinum-Based Chemotherapy Hye Jung Park, Chein-Soo Hong, Jae-Hyun Lee, Jae-Hyun Lee, Sungryeol KIM, Sungryeol KIM, Kyung Hee Park, Kyung Hee Park, Choong-Kun Lee, Beodeul Kang, Seung-Hoon Beom, Sang Joon Shin, Minku Jung, Jung-Won Park, Jung-Won Park A228 Anti-Allergic Effect of Intralymphatic Injection of OVA-Flagelin Mixture in Mouse Model of Allergic Rhinitis Eun-Hee Kim, Ji-Hye Kim, Ji-Hun Mo, Young-Jun Chung A229 Serum Periostin Level Is Higher in Respiratory Type of NSAID Hypersensitivity Than Cutaneous Type Mi-Ae Kim, Hae-Sim Park, Moon Gyeong Yoon, Young-Soo Lee, Ji Hye Kim, Ga Young Ban, Hye-Soo Yoo, Yoo Seob Shin, Young Min Ye, Dong-Ho Nahm A230 A Retrospective Analysis of Allergy Blood Testing in Beijing Children’s Hospital in the Year of 2013: A Single-Center Research Qing Miao, Li Xiang A231 Role of Nrf2 in the Allergic Airway Inflammation Differ Between BALB/c and C57BL/6 Mice Ying-Ji Li, Takako Shimizu, Hirofumi Inagaki, Yukiyo Hirata, Hajime Takizawa, Arata Azuma, Masayuki Yamamoto, Tomoyuki Kawada A232 Effect of Human Mesenchymal Stem Cell on Neutrophilic Asthma Model Min-Gu Kim, Gyong Hwa Hong, Kyoung Young Lee, Eun Hee Ha, Keun Ai Moon, Sunjoo Park, Hyouk-Soo Kwon, Tae-Bum Kim, Hee-Bom Moon, You Sook Cho, Jung-Hyun Kim, Hyo-Jung Kim, So-Young Park, Bomi Seo A233 Immunomodulatory Effect of Tonsil Derived Mesenchymal Stem Cells in a Mouse Model of Allergic Rhinitis Ji-Hye Kim, Ramachandran Samivel, Eun-Hee Kim, Young-Jun Chung, Ji-Hun Mo A234 Alternative Therapy Such As Yoga May be a Low Cost Tool for Improving the Quality of Life of Patient’s with Allergic Rhinitis and Asthma Soumya M. S., G. Inbaraj, R. Chellaa, Ruby Pawankar A235 Substantial Impairment of the Quality of Life in Adult Patients with Chronic Urticaria Wonsun Choi, Hae-Sim Park, Young Min Ye, Ji Hye Kim, Ga Young Ban, Yoo-Seob Shin A236 Dietary Galacto-Oligosaccharides Reduce Airway Eosinophilia and Enhance the Th2 Suppressive Effect of Budesonide in House Dust Mite-Induced Asthma in Mice Saskia Braber, Kim Verheijden, Aletta Kraneveld, Johan Garssen, Linette Willemsen, Gert Folkerts A237 Production and Characterization of Recombinant Periplaneta americana Allergens for Component Resolved Diagnosis Stephanie Eichhorn, Fatima Ferreira, Isabel Pablos, Bianca Kastner, Bettina Schweidler, Sabrina Wildner, Peter Briza, Jung-Won Park, Naveen Arora, Stefan Vieths, Gabriele Gadermaier A238 Assessment of Characteristics of Itch in Patients with Hand Eczema Sung-Min Park, Won-Ku Lee, Jeong-Min Kim, Gun-Wook Kim, Je-Ho Mun, Hoon-Soo Kim, Margaret Song, Hyun-Chang Ko, Moon-Bum Kim, Byung Soo Kim A239 The Hidden Culprit: A Case of Repeated Anaphylaxis from Cremophor Hypersensitivity. Young Nam Kim, Sehyo Yune, Jin-Young Lee, Jihye Kim, Young Eun Kim, Jae-Won Paeng, Mi-Jin Jang, Dong-Chull Choi, Byung-Jae Lee, Yongseok Lee A240 Spectrum of Anaphylaxis in Children and Adults at Emergency Departments in Singapore Si Hui Goh, Bee Wah Lee, Jian Yi Soh A241 Improved Quality of Life through an Integrated Health Care Service for Children with Atopic Dermatitis Hyungoo Kang; Hyunhee Kim; Hye-Yung Yum A242 Criteria Combining Autologous Serum Skin Test and Clusterin for Predicting Antihistamine-Refractoriness in Patients with Chronic Spontaneous Urticaria Young Min Ye; Hae-Sim Park; Ga-Young Ban; Ji Hye Kim; Yoo Seob Shin A243 Urinary Leukotriene E4 Levels in Wheezing Infants Takumi Takizawa, Masahiko Tabata, Akira Aizawa, Hisako Yagi, Yutaka Nishida, Hirokazu Arakawa, Akihiro Morikawa, Solongo Orosoo A244 Allergic Sensitization to Whey in Mice Is Facilitated By the Mycotoxin Deoxynivalenol (DON) Saskia Braber, Marianne Bol-Schoenmakers, Peyman Akbari, Prescilla V. Jeurink, Prescilla V. Jeurink, Priscilla De Graaff, Joost J. Smit, Betty C. A. M. Van Esch, Johan Garssen, Johan Garssen, Johanna Fink-Gremmels, Raymond H. H. Pieters A245 How to Define Chronic Cough: Based on a Systematic Review of the Epidemiological Literature Gun-Woo Kim, Eun-Jung Jo, Sujeong Kim, Woo-Jung Song, Yoon-Seok Chang, Shoaib Faruqi, Ju-Young Kim, Mingyu Kang, Min-Hye Kim, Jana Plevkova, Heung Woo Park, Sang-Heon Cho, Alyn Morice, So-Hee Lee, Sun-Sin Kim, Seoung-Eun Lee A246 Asko Study: Comparison of Behavior and Habits in Diagnosis and Treatment of Adult Asthma and COPD Patients Bilun Gemicioglu, Zeynep Misirligil, Arif Hikmet Cimrin, Hakan Gunen, Tevfik Ozlu, Aykut Cilli, Levent Akyildiz, Hasan Bayram, Esra Uzaslan, Oznur Abadoglu, Mecit Suerdem A247 Changes in Pulmonary Function in the Treatment of Obesity in Children Keigo Kainuma A248 Changes of Feno and Nasal Feno Levels after Treatment in Pediatric Allergic Rhinitis Hyun-a Kim, Ha-Su Kim, Woo Yong Bae, Jin-a Jung A249 Prevalence of Vitamin D Deficiency in Exclusively Breastfed Infants in Kenya Rose Kamenwa, William Macharia, Nusrat Said A250 In-Vitro Screening of Atopy in the Indian Population: Are Current Methods Adequate, Keeping Local IgE Seroprevalence for Common Food & Inhalant Allergens in Mind? Vidya Nerurkar, Meenal Patel, Simi Bhatia A251 Usefulness of House Dust Mites Nasal Provocation Test in Asthma Inseon S Choi, Soo-Jeong Kim, Joo-Min Won, Myeong-Soo Park A252 Biomarker-Based Treatment Option for Preschool Children with Recurrent Wheeze Mizuho Nagao A253 Anti-Tuberculosis Drugs-Induced Liver Injury in Patients with Connective Tissue Diseases Dong Won Park, Jang Won Sohn, Ji Young Yhi, Ji-Yong Moon, Sang-Heon Kim, Tae Hyung Kim, Dong Ho Shin, Ho Joo Yoon A254 Ocular Symptoms of Cedar Pollinosis in Otolaryngology Patients Yukiyoshi Hyo A255 The Clinical Characteristics of Adverse Drug Reactions Reported in a Regional University Hospital for 6 Years and the Suggestions for the Reporting System Jaechun Lee, Su Hee Kim, Eunkyoung Lee A256 Changes in Skin Prick Test Results over 3 Years in School-Aged Children Hahn Jin Jung, Jaehyun Lim, Seung-No Hong, Doo Hee Han, Chae-Seo Rhee A257 The Analysis of Risk Factors and Features of Food Allergy in Korean Children: Nationwide Cross-Sectional Survey Kun Song Lee A258 A Sequential Indirect-Direct Bronchial Provocation Test for Diagnosis of Asthma: A Pilot Study Jaechun Lee, Sun Young Yang, Mi Young Ahn, Jong Hoo Lee, Jasmina Golez A259 Association of VDR and CYP2R1 Polymorphisms with Persistent Allergic Rhinitis in a Han Chinese Population Hui-Qin Tian, Lei Cheng, Xin-Yuan Chen A260 Associations of Metabolic Syndrome with Asthma and Atopy in Korean Adults Ji-Yong Moon, Sang-Heon Kim, Tae Hyung Kim, Ji Young Yhi, Ho Joo Yoon, Jang Won Sohn, Dong Ho Shin, Dong Won Park A261 Clinical Manifestation and Treatment Outcome of Eosinophilic Gastroenteritis in Korean Children Won Im Cho, Jong Sub Choi, Dongin Suh, Gyeong Hoon Kang, Jin Soo Moon, Jae Sung Ko, Kyung Jae Lee, Shin Jie Choi A262 The Sensitization Model and Correlation of Bermuda and Timothy Grass Pollen Allergen in Allergic Patients in Southern China Wenting Luo, Baoqing Sun A263 A Pilot Study on the Outcomes of Respiratory Allergic Diseases at Pre-School Age in Chinese Infants with Atopic Dermatitis Qi Gao, Li Xiang, Kunling Shen A264 Activation of Toll like Receptor 1 and 6 By House Dust Mite Enhances the Expression of Tight Junction Protein in Epidermal Keratinocytes Yong Hyun Jang A265 Pollen Exposure in a Mobile Exposure Chamber: Comparing Real-Life Symptoms with Exposure Symptoms Karl-Christian Bergmann, Torsten Sehlinger, Georg Bölke, Uwe Berger, Torsten Zuberbier A266 Retrospective Analysis of the Incidence of Allergy in Patients with Contact Eczema Joanna Kolodziejczyk, Milena Wojciechowska, Anna Hnatyszyn-Dzikowska, Micha Chojnacki, Zbigniew Bartuzi A267 Effect of Fungal Sensitization in Patients with Severe Asthma Katsunori Masaki, Koichi Fukunaga, Takashi Kamatani, Kengo Ohtsuka, Takae Tanosaki, Masako Matsusaka, Takao Mochimaru, Hiroki Kabata, Soichiro Ueda, Yusuke Suzuki, Katsuhiko Kamei, Koichiro Asano, Tomoko Betsuyaku A268 SCIg Patient Preference Pump Versus Push Karlee Trafford A269 Fixed Drug Eruption Induced By Ornidazole and Diclofenac Ismet Bulut, Zeynep Ferhan Ozseker A270 Transepidermal Water Loss Measurement during Infancy Can Predict the Subsequent Development of Atopic Dermatitis Kenta Horimukai, Hideaki Morita, Masami Narita, Hironori Niizeki, Kenji Matsumoto, Yukihiro Ohya, Hirohisa Saito, Shigenori Kabashima, Mai Kondo, Eisuke Inoue A271 Inhalant Allergens on Soft Toys: A Literature Review Robert Siebers, Francis FS Wu A272 Fractional Exhaled Nitric Oxide in Elderly Asthmatics Robert Siebers, Francis FS Wu, Ming-Hui Ting, Hung-En Laio, Tsung-Huai Kuo, Pei-Yuan Lee A273 Dye and Preservative Challenge in Meal-Associated Urticaria and Angioedema: A Low-Yield Diagnostic Maneuver Daniel Eugene Maddox A274 The Changes of Allergic Sensitization with Age in Children with Allergic Rhinitis Gwanghui RyuHyo Yeol Kim, Hun-Jong Dhong, Sang Duk Hong, Seung-Kyu Chung A275 Component-Specific IgE and IgG4 Levels in Milk Allergy Children Tolerated Baked Milk Products Osamu Higuchi, Yu-Ichi Adachi, Toshiko Itazawa, Yoko Adachi, Miki Hamamichi, Motokazu Nakabayashi, Yasunori Ito, Takuya Wada, Gyoukei Murakami, Miki Takao, Junko Yamamoto A276 Serum Surfactant Protein(SP)-D Level: A Potential Biomarker for Aspirin-Exacerbated Respiratory Disease Hyun Jung Jin, Moon Gyeong Yoon, Young Min Ye, Yoo-Seob Shin, Seung-Hyun Kim, Hae-Sim Park A277 Clinical Characteristics of Anaphylaxis in Korean Children Taek-Ki Min, Bok-Yang Pyun, So-Yeon Lee, Hyun Hee Kim, Gwang-Cheon Jang, Jinho Yu, Dongin Suh, Sooyoung Lee, Yong Mean Park, Jeong Hee Kim, Hye-Yung Yum, Kyung Won Kim, Hyeon-Jong Yang, Kangmo Ahn, Ji-Won Kwon, Myung Hyun Sohn, Hae Ran Lee, Jung Hyun Kwon, Kyu-Earn Kim, Soo-Jong Hong A278 Immunological Changes Induced By Intramuscular Injections of Autolologous Immunoglobulin in Patients with Severe Atopic Dermatitis Su-Mi Cho A279 Identification of Subtypes in Subjects with Mild to Moderate Airflow Limitation and Their Clinical and Socioeconomic Implications Jin Hwa Lee, Chin Kook Rhee, Hye Yun Park, Woo Jin Kim, Yong Bum Park, Kwang-Ha Yoo A280 Cephalosporin-Induced Dress (Drug Rash with Eosinophilia and Systemic Symptoms) Syndrome in a 7-Year-Old Boy Heejeong Kang, Hyeon-Jong Yang, Taek-Ki Min, Bok-Yang Pyun A281 Maternal Depression Is Associated with Children’s Asthma : An Analysis of the Fifth Korea National Health and Nutrition Examination Survey (2010-2012) Lee Ju Suk, Cheol Hong Kim A282 Increased Length of Hospitalization Associated with Infiltration on Chest Radiography in Pediatric Asthma Patients Jung Hyun Kwon, Sang Hyun Lee, Wonhee Seo A283 A Case of 16-Year-Old Boy with Smoking-Induced Acute Eosinophilic Pneumonia Kang-in Kim, Young Cheon Park, Hyeon-Jong Yang, Taek-Ki Min; Bok-Yang Pyun A284 A Case of Pranlukast Induced Anaphylactic Shock Sujeong Kim, Sun Jin, Jong-Myung Lee, Hye-Jin Jung, Jung-Wha Park A285 Comparison of Asthma-Related Outcomes Between Metabolically Healthy Obese and Metabolically Unhealthy Obese Asthma Patients Hyo-Jung Kim, Tae-Bum Kim, You Sook Cho, Hee-Bom Moon, Hyouk-Soo Kwon, So Young Park, So-Young Park, Jung-Hyun Kim, Bomi Seo, Min-Gu Kim, Youn Yee Kim A286 Rick Factors Associated with Longer Length of Stay in Infants Hospitalized with Respiratory Syncytial Virus Bronchiolitis Yena Lee, Taek-Ki Min, Hyeon-Jong Yang, Bok-Yang Pyun, Suk Hee Han, Suyeon Park, Jeongho Lee, Won-Ho Hahn A287 Urinary Excretion of 9α, 11Î(2)-Prostaglandin F(2) and Leukotriene E(4) in Patients with Exercise-Induced Bronchoconstriction Youhoon Jeon, Joo-Hee Kim, Tae-Rim Shin, Cheol-Hong Kim, In-Gyu Hyun, Jeong-Hee Choi A288 The Aeroallergen Sensitization Pattern and Effect on Airway Hyperresponsiveness in Busan, Korea Sun-Mi Jang, Hae-Jung Na, Seung-Eon Song, Hye-Kyung Park, Eun-Jung Jo A289 Multicenter Questionnaires on Current Management of Atopic Dermatitis Among Korean Patients and Caregivers Dong Hun Lee, Jin-Young Lee, Yang Park, Jae-Won Oh, Mi Hee Lee, Soo-Jong Hong, Soo-Jong Hong, So-Yeon Lee, Joon Soo Park, Dong-Ho Nahm, Hye-Yung Yum, Hye-Yung Yum A290 Der p 1, Der p 2 and Der p 10 IgE Reactivities in Allergic Rhinitis Patients in Korea Kyu Young, Dong-Young Kim A291 De-Labeling Beta-Lactam Hypersensitivity: An Experience from a Tertiary Care Hospital in Thailand Sirinoot Palapinyo; Jettanong Klaewsongkram A292 Sonic Hedgehog Signaling: Evidence for Its Protective Role in Endotoxin Induced Acute Lung Injury Mouse Model Xing Chen, Yuting Jin, Xiaoming Hou, Fengqin Liu, Chunyan Guo, Yulin Wang A293 Analyses of the Factors behind the Negative Attitudes Toward the Administration of Adrenaline Auto-Injectors in School Settings Ikuo Okafuji, Yuya Tanaka, Shegeyuki Narabayashi, Satoru Tsuruta A294 Low Vitamin D Levels Are Related to High House Dust Mite Sensitization in Patients with Severe Atopic Dermatitis Yong Hyun Jang A295 Appendicular Skeletal Muscle Mass Index: A Potential Predictor of Skeletal Muscle Abnormality According to the Severity Airflow Limitation of COPD Jun-Hong Ahn, Dong-Won Lee, Jin Hong Chung, Hyun Jung Jin, Min-Su Sohn A296 Etiology and Clinical Feature of Oral Allergy Syndrome in Children Young a Park, Kyunguk Jeong, Yoon Hee Kim, In Suk Sol, Seo Hee Yoon, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim, Sooyoung Lee A297 Traffic-Related Pollution Levels and Poorly Controlled Asthma in Adults Ho Kim, Ja Yeun Kim A298 Anaphylaxis in Korean Children, 2009-2013 : Triggers of Anaphylaxis By Age Groups So-Yeon Lee, Taek-Ki Min, Tae-Won Song, Kangmo Ahn, Jihyun Kim, Gwang-Cheon Jang, Hyeon-Jong Yang, Bok-Yang Pyun, Ji-Won Kwon, Myung Hyun Sohn, Kyu-Earn Kim, Jinho Yu, Soo-Jong Hong, Jung-Hyun Kwon, Sung-Won Kim, Sooyoung Lee, Woo Kyung Kim, Hyung Young Kim, Hye-Young Kim, Youhoon Jeon A299 Maternal Allergy Is Associated with Acute Bronchiolitis Severity in Infant Chang Hoon Lim, Yeongsang Jeong, Su Jung Kim A300 Evaluation of Inflammatory Mediator Profiles in Sputum of Asthmatics As an Endotype for Refractory Asthma Hun Soo Chang, Jeong-Seok Heo, Da-Jeong Bae, Jong-Uk Lee, Ji-Na Kim, Chang-Gi Min, Hyun Ji Song, Jong-Sook Park, Soo Hyun Kim, Choon-Sik Park A301 Autophagy Is Associated with the Severity of Asthma in an Ovalbumin-Specific Mouse Model of Allergic Asthma Jing-Nan Liu, Youngwoo Choi, Yoo Seob Shin, Hae-Sim Park A302 Interleukin-9 and Interleukin-33 Levels in Children with Asthma Nima Rezaei, Sedigheh Bahrami Mahneh, Arezou Rezaei, Maryam Sadr, Masoud Movahedi A303 Pediatric Anaphylaxis at a University Hospital in Cheonan, Korea, 2013~2014 Jun Seak Gang, Joon Soo Park, Seung Soo Kim, Hyun Ho Bang, Kyeong Bae Park, Hye Sun Kim, Tae Ho Kim, Young Hwangbo, Hyun Jung Lee, Gyeong Hee Yoo, Young Chang Kim A304 Initial Antigen-Specific IgE Levels Predict Clinical Outcome of Rush Oral Immunotherapy for Food Anaphylaxis Sakura Sato, Noriyuki Yanagida, Motohiro Ebisawa A305 ABCC4 gene Polymorphism Is Associated with High Periostin Levels in Asthmatic Patients Sailesh Palikhe, Hae-Sim Park, Seung-Hyun Kim, Ri-Yeon Kim, Eun-Mi Yang A306 The Role of Clinical Phenotype and Allergen Sensitization at 2 Years As Predictors of Atopic Disorders at 5 Years Li Yuan Gabriella Nadine Lee, Marion Aw, Marion Aw, Bee Wah Lee, Bee Wah Lee, Evelyn Xiu Ling Loo, Yiong Huak Chan, Lynette Shek, Lynette Shek, I-Chun Kuo, I-Chun Kuo, Phaik Ling Quah, Phaik Ling Quah, Genevieve Llanora, Gerez Irvin A307 The Effect of Korean Red Ginseng (KRG) on Rhinovirus Infection in Human Nasal Epithelial Cells Joo Hyun Jung, Il Gyu Kang, Seon Tae Kim, Hyoungmin Park A308 The Effect of Korean Red Ginseng on the Symptoms and Allergic Inflammation in Patients with Allergic Rhinitis Seon Tae Kim, Joo Hyun Jung, Il Gyu Kang, Hyoungmin Park, Kwang-Pil Ko A309 Validation of the Newly Developed Multiple Allergen Simultaneous Test in Korea Jungsoo Lee, Howard Chu, Hemin Lee, Jung U Shin, Chang Ook Park, Kwang Hoon Lee, Kwang Hoon Lee, Hong Kyu Kang A310 Assessment of Symptoms Severities of Allergic Rhinitis Patients Sensitive to Multiple Allergens in Skin Prick Test Dong Chang Lee, Geun Jeon Kim, Jae Hyung Hwang, Jin Bu Ha, Su Hee Jeong A311 Diurnal Temperature Range and Emergency Department Visits for Asthma in Korea 6 Cities Ho Kim, Shinha Hwang, Whahee Lee A312 Mannan-Binding Lectin Serum Levels in Atopic Mongolian Adults Enkhbayar Bazarsad, Logii Narantsetseg, Munkhbayarlakh Sonomjamts A313 Prevalence of Doctor Diagnosed Atopic Eczema, during 2003-2014 in KOREA ; Using Big Data of 48.1 Million South Korean Health-Care Records Gwang-Cheon Jang, Hyun-Hee Lee, Chang-Jong Lee, Huynsun Lim A314 Association of Recurrent Wheeze with Lung Function and Airway Inflammation in Preschool Children Ji-Eun Soh, Dae-Jin Song, Ji-Won Kwon, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, So-Yeon Lee, Gwang-Cheon Jang, Woo Kyung Kim, Young-Ho Jung, Soo-Jong Hong, Jung Yeon Shim A315 Mannan-Binding Lectin Serum Levels in Healthy Mongolian Adults Enkhbayar Bazarsad, Logii Narantsetseg, Munkhbayarlakh Sonomjamts A316 Rotanebuliser Prabhakarrao Pv, Ranjitha Nadendla A317 The Level of Serum Interleukin 13 and Interleukin 17A and Its Effect Factors in Children with Asthma Juan Fang, Jing Zhao A318 Is Vitamin D Insufficiency Also Involved in Childhood Asthma in South Korea? Dae-Jin Song, Sungchul Seo, Young Yoo, Yu-Ri Kim, Ji Tae Choung, Jee Hoo Lee A319 Collection of Nasal Secretions for Measurement of Local IgE: A Quest for the Best Method Margot Berings, Natalie De Ruyck, Claus Bachert, Philippe Gevaert, Gabriële Holtappels A320 The Role of Claudin 5 in a Murine Model of Asthma Pureun-Haneul Lee, Byeong-Gon Kim, Choon-Sik Park, George D Leikauf, An-Soo Jang A321 Claudin-4 in a Murine Model of Asthma: Modulation By Acrolein, a Highly Reactive Unsaturated Aldehyde Byeong-Gon Kim, Pureun-Haneul Lee, Choon-Sik Park, An-Soo Jang A322 Efficacy and Safety of Sublingual Immunotherapy in House Dust Mite Sensitized Children with Allergic Rhinitis Yang Park A323 The Association of Vitamine D Deficiency and Skeletal Muscle Dysfunction in Chronic Airway Disease Min-Su Sohn, Hyun Jung Jin, Dong-Won Lee, Jun-Hong Ahn, Jin Hong Chung A324 Bacteria Derived Extracellular Vesicles in Indoor Dust Is Closely Associated with Airway Disease and Lung Cancer: Analysis of Indoor Dust’s Microbiome and IgG Sensitization of Indoor Bacteria Derived Extracellular Vesicles Sae-in Kim, Han-Ki Park, Do-Yeon Kim, Mina Rho, Jun-Pyo Choi, Yoon-Keun Kim A325 Clinical Care Program for Childhood Asthma (CCP-Childhood Asthma); A Multidisciplinary Team Care at Samitivej International Children’s Hospital Wasu Kamchaisatian, Thitikul Hiranras, Surinda Wongpun, Phornthip Chiraphorn, Anupan Tantachun, Wannipa Wongrassamee, Planee Vatanasurkitt, Naratip Somboonkul, Nattipat Juthacharoenwong, Surangkana Techapaitoon, Montri Tuchinda A326 Continuous B Cell Stimulation with CD40 Ligand Induce IgE Isotype Switching Jae Ho Lee, Sejin An A327 Effects of Interleukin-9 on Allergen-Specific Immunotherapy in a Mouse Model of Allergic Rhinitis Ji-Hyeon Shin, Soo Whan Kim, Si Won Kim, Jun Myung Kang, Boo-Young Kim, Byung-Guk Kim A328 Usefulness of Exhaled Nitric Oxide for Evaluating Wheeze and Airway Hyperresponsiveness in Preschool Children Jung-Won Lee, Ji-Won Kwon, Woo Kyung Kim, Hyung Young Kim, Hyo-Bin Kim, Ju-Hee Seo, So-Yeon Lee, Gwang-Cheon Jang, Young-Ho Jung, Soo-Jong Hong, Byoung-Ju Kim, Dae-Jin Song, Jung Yeon Shim A329 Systemic Cyclosporine Treatment in Hand Eczema Patients Kyung Ho Kim A330 Lipid Profiles and Adipokines in Korean Children with Atopic Dermatitis Young Yoo, Won Suck Yoon, Sungchul Seo, In Soon Kang, Jae Won Choi, Hye-Young Lim, Ji Tae Choung A331 Validation of Montelukast and Levocetirizine Combination Tablet Versus Individual Tablets in the Treatment of Moderate to Severe Persistent Allergic Rhinitis Among Adult Filipinos Seen at the Philippine General Hospital-Outpatient Department Michelle Buela A332 Efficacy of Makyokansekito on Treatment of Wheezing Lower Respiratory Tract Infection in Children: A Retrospective Study of 68 Patients Koji Nishimura A333 Serum Eosinophilia and Total IgE Are Associated with the Risk of Allergic Sensitization and Allergic Symptoms in Two Years Follow-up, Respectively Sang Chul Park, Hyo Jin Chung, Chang-Hoon Kim, Ju Wan Kang, Seong-Chul Hong, Keun-Hwa Lee, Jaechun Lee, Hye-Sook Lee, Jeong Hong Kim A334 The Sensitization to Russian Thistle on Mongolian Patients Narantsetseg Logii A335 The Association Between Air Pollution, Allergic Sensitization to Inhalant Allergens and Airway Hyperresponsiveness in Ulaanbaatar, Mongolia Munkhbayarlakh Sonomjamts, Enkhbayar Bazarsad A336 Pre-Coseasonal Treatment with a 5-Grass Pollen Sublingual Tablet in Adults Demonstrated a Reduction on Asthma Symptoms in Réunion Island Bashir Omarjee A337 Peak Expiratory Flow Rate Reference Values for Children Aged 5-14 Years Old in Beijing Urban Area Shuo LI A338 Soybean Storage Proteins As the Main Allergen in a Patient with Food-Dependent Exercise-Induced Anaphylaxis Due to Tofu Miyuki Hayashi, Ruby Pawankar, Shingo Yamanishi, Toru Igarashi, Yasuhiko Itoh A339 A Study of Allergy Skin Prick Test with Weed Pollen Oyuntsatsral Batsaikhan, B. Gantulga, B. Enkhbayar, S. Munkhbayarlakh, L.Narantsetseg A340 The Role of Neurotrophin in a Murine Model of House Dust Mite Induced Allergic Rhinitis Pei-Chi Chen, Jiu-Yao Wang A341 Mimotopes of the Major Shellfish Allergen Tropomyosin Suppress Splenocyte Proliferation and Local Cytokine Expression in a Mouse Model of Shellfish Allergy Nicki Y. H. Leung, Christine Yee Yan Wai, Patrick S.C. Leung, Ka Hou Chu A342 A Questionnaire Survey on Understanding of Atopic Dermatitis Among Korean Patients and Caregivers Eun Jin Doh, Dong Hun Lee, Mira Choi, Hyun-Sun Yoon, Kyu Han Kim, Ji Soo Lim A343 Comparison of the Dosage of Bronchodilators in the Bronchodilator Response Test in Children Ji Hyeon Baek, Man Yong Han, Seung Jin Lee, Youhoon Jeon, Kyung Suk Lee, Young-Ho Jung, Hye Mi Jee, Youn Ho Shin A344 The Expression and Effect of Natural Killer T Lymphocytes in Chidren with Asthma Yi Jiang, Miao Liu A345 Oral Provocation Test in Non-Steroidal Anti-Inflammatory Drug Hypersensitive Patients Referred to Singapore General Hospital Chaw Su Naing, Tze Chin Tan, Yong Yeow Chong A346 Different Phenotypes of Bhr (bronchial hyperresponsiveness) By Natural Course in Children and It’s Characteristics Young-Ho Kim, Eun Lee, Song-I Yang, Hyun-Ju Cho, Hyung Young Kim, Ji-Won Kwon, Young-Ho Jung, Byoung-Ju Kim, Ju-Hee Seo, Ho-Jang Kwon, Hyo-Bin Kim, So-Yeon Lee, Soo-Jong Hong, Soo Hyun Kim A347 Spectrum of Allergens Causing Allergic Rhinitis and Asthma in Urban Bangalore, India − a Study of 120 Patients Jacqueline Elizabeth Joseph, Soumya M. S, Ruby Pawankar, Harshitha Kumar A348 High Prevalence of Wheezing Illness and Risk Factor of Atopic Asthma Progression in Korean Preschool Children Sohyoung Yang, Sung-Il Woo A349 Clinical and Laboratory Screening of Primary Immunodeficiency Diseases: International Effects Nima Rezaei A350 The Effect of Helicobacter Pylori Infection in Atopic Individuals Sukran Kose, Basak Gol Serin, Arzu Didem Yalcin, Süheyla Serin Senger, Mehmet Erden, Ertan Serin A351 Clinical Spectrum and Natural History of Chronic Urticaria in Hong Kong Children Agnes Sze-Yin Leung, Ting Fan Leung A352 Skin Prick Test Reactivity to Common Pollen Aeroallergens in Patients with Allergic Rhinitis − in Urban Bangalore, India Harshitha Kumar, Soumya M.S., Jacqueline Elizabeth Joseph, Ruby Pawankar A353 Seasonal Patterns of Asthma-Related ED Visits and Admissions in Children and Adolescents Who Visited Emergency Rooms of Korea in 2007-2012 Eun Hee Chung A354 Prevalence of Atopic Dermatitis and Its Associated Risk Factors in Elementary School Children: A Cross-Sectional Study in Gyeonggi-Do, South Korea Eunji Kim, Young Yoo, Ji Tae Choung, Sungchul Seo, In Soon Kang, Jue Seong Lee, Ji Hyen Hwang A355 Intralymphatic Immunotherapy for Dermatophagoides Farinae, Dermatophagoides Pteronyssinus, Cat, and/or Dog Allergy in Patients with Allergic Rhinitis: 1 Year Follow-up Sang Min Lee, Joo Hyun Jung, Seung Joon Choi, Eugene Joe, Hyunjung Hwang, Shin Myung Kang, Yu Jin Kim, Sun Young Kyung, Jeong-Woong Park, Sung Hwan Jeong, Sang Pyo Lee A356 Respiratory Syncytial Virus Regulates IL-33 Expression in Bronchoalveolar Cells and Lung Tissue in Vivo Alina Gaisina, Igor Shilovskiy, Aleksandra Nikonova, Oleg Kamyshnikov, Musa Khaitov, Alexander Mitin, Komogorova Viktoriya, Marina Litvina, Nina Sharova A357 The Prevalence of Parent-Perceived Food Hypersensitivity in Pre-School Children Attending a Tertiary Care Hospital in Malaysia Faizah Mohamed Jamli A358 Th2 Dominant Airway Inflammation Induced By House Dust Mite Chitin Is Dependent on TNF-a and NKT Cell Da-Il Yoon, Jun-Pyo Choi, Han-Byul Choi, Yoon-Keun Kim, Hyeon-Il Choi A359 Geographic Variations in the Patterns of Sensitization to Aeroallergens in Korean Adults: A Multi-Center Study Mingyu Kang, Mi Yeoung Kim, Sujeong Kim, Eun-Jung Jo, Seoung-Eun Lee, Woo-Jung Song, Sang Min Lee, Chansun Park, Yoon-Seok Chang, Jaechun Lee, Young-Koo Jee, Inseon S Choi, Kyung-up Min, Sang-Heon Cho A360 Experimental Mouse Model of Asthma Induced By Dust Mite Dermatophagoides Pteronyssinus allergenic Extract Anton Laskin, Oleg Kamyshnikov, Alexander Babakhin, Valentina Berzhets, Musa Khaitov A361 Severe Refractory Pulmonary Complications in Children with Mycoplasma Pneumoniae Pneumonia Sejin An, Jae Ho Lee A362 Usefulness of Interactive e-Learning Education Program for Asthma Guideline Sung-Yoon Kang, Yoon-Seok Chang, Kyung-up Min, Sang-Heon Cho, Sae-Hoon Kim, Yong Eun Kwon, Young-Koo Jee, Tae-Bum Kim, Hee-Bom Moon, Hye-Kyung Park A363 Airway Inflammation Induced By House Dust Mite Derived Vesicles Is Mainly Induced By LPS Derived from Gram Negative Bacteria in Dust Mite. Sang-Yoon Kim, Jun-Pyo Choi, Han-Ki Park, Ji-Hyun Lee, Yoon-Keun Kim A364 Changes in the Recognition of Causal Allergen, Its Avoidance, and Allergen Specific Immunotherapy after Skin Prick Test / Intradermal Test, Nasal Provocation Test, and Intralymphatic Immunotherapy in Patients with Allergic Rhinitis: 1 Year Follow-up Hyunjung Hwang, Eugene Joe, Sang Min Lee, Seung Joon Choi, Joo Hyun Jung, Yong Han Seon, Shin Myung Kang, Yu Jin Kim, Sun Young Kyung, Jeong-Woong Park, Sung Hwan Jeong, Sang Pyo Lee A365 Laboratory Diagnostic of Staphylococcal Sensitization Natalya Khramykhoverchenko A366 Th-17 Regulatory Cytokines Enhance Neutrophil Production of IL-17 during Asthma Saleh Al Muhsen, Asma Sultana, Rabih Halwani, Ahmed Bahammam A367 Diagnostic Value of Serum Total IgE and Prediction of Cut-Off Value to Recommend Mast in Allergic Rhinitis Hyung Chae Yang, Sun Kyung Kim, Kwang Il Nam A368 Diagnostic Value of an Increase in FEV1 and/or FVC >12% and >200 mL from Baseline after Bronchodilators for Diagnosis of Asthma Jeong-Eun Kim, Ju Suk Lee, Ji Hyun Lee, Kyung Woo Kang A369 Combined Use of Fractional Exhaled Nitric Oxide and Bronchodilator Response in Predicting Future Loss of Asthma Control Among Children with Atopic Asthma Je-Kyung Kim, Youn-Soo Hahn, Jae-Yub Jung A370 Antigen-Specific IgA Plays an Important Role in Mucosal Immune Response in Allergic Children : Measurement of Secretory IgA and Antigen-Specific IgA Yosuke Baba, Sususmu Yamazaki, Eisuke Inage, Mari Mori, Yoshikazu Ohtsuka, Masato Kantake, Toshiaki Shimizu, Asuka Honjoh, Tomoaki Yokokura A371 Why Teaching Pediatrics Trainees about Anaphylaxis and Its Acute Management Is Essential: Cross Sectional Survey. Mehdi Adeli, Shaza Ali Mohammed Elhassan, Caroline Beck A372 Prevalence and Clinical Characteristics of Local Allergic Rhinitis in Children Min Sun Na, Heysung Baek, Seung Jin Lee, Ji Hyeon Baek, Jungwon Yoon, Sun Hee Choi, Young-Ho Jung, Youn Ho Shin, Man Yong Han A373 House Dust Mites Sublingual Immunotherapy Can Influence the Long-Term Evolution of Severe Atopic Dermatitis and the Progression to Respiratory Allergy. Enrico Compalati, Maurizio Marogna A374 The Positive Distribution Characteristics of 90 Food Specific IgG in Patients with Allergic Diseases Huimin Huang, Baoqing Sun, Mingyu BAI, Yiting Huo, Peiyan Zheng, Nili Wei, Wenting Luo A375 Evaluation of Serum Levels of Osteopontin As a Potential Biomarker of Immune Activation in Patients with Allergic Diseases Elisa Villa, Anand Andiappan, Rosalba Minisini, Olaf Rötzschke, Elena Boggio, Luca Gigliotti, Nausicaa Clemente, Annalisa Chiocchetti, Umberto Dianzani, Mario Pirisi A376 Prevalence of Allergic Rhinitis in 3-6-Year-Old (preschool) Children in Chiba City (urban area), Japan Fumiya Yamaide, Syuji Yonekura, Naoki Shimojo, Yuzaburo Inoue, Yoshitaka Okamoto A377 Comparative Efficacy of Combination Nebulized Salbutamol and Fluticasone Propionate and Nebulized Salbutamol in Children with Mild Moderate Asthma Attack Retno Asih Setyoningrum, Landia Setiawati, Sri Sumei, Deddy Iskandar A378 Characteristics of Children Hospitalized with Asthma in West Nusa Tenggara General Hospital Mataram Indonesia Indriyani Sang Ayu Kompiyang A379 Identification of Phenotypes in Allergic Bronchopulmonary Aspergillosis Using Cluster Analysis Tsuyoshi Oguma, Jun Tanaka, Katsuyoshi Tomomatsu, Koichiro Asano A380 The Roles of Type 2 Innate Lymphoid Cells (ILC2) in Chronic Rhinosinusitis (CRS) Keisuke Uno, Yoshinori Matsuwaki, Kazuhiro Omura, Eika Hayashi, Norifumi Tatsumi, Hirohito Kita, Nobuyoshi Otori, Hiromi Kojima A381 Respiratory Symptoms, Signs and Spirometry Indexes Comparision in 7-12 Years Old Girls in Esfahan Metropolis and Its Far Suburb Mohammadreza Fatemi Khorasgani A382 Induction of Kruppel-like Transcription Factor (KLF4&5) By Baker’s Yeast Mannan in Human Bronchial Epithelial and Smooth Muscle Cells Dukhee/Betty Lew, Kim/S. Lemessurier, Joseph/a Moore, Jeoung-Eun Park, Ae-Kyung Yi, Chi/Young Song, Kafait/U Malik A383 Korean Profile in Childhood Asthma Severity Classification Dongin Suh, Ja Kyoung Kim, Hyeon-Jong Yang, Bong-Seong Kim, Youn Ho Shin, So-Yeon Lee, Geunhwa Park, Woo Kyung Kim, Hyo-Bin Kim, Heysung Baek, Dae Hyun Lim, Dae Hyun Lim, Jin Tack Kim A384 Prevalence of Food Sensitization, IgE-Mediated and Non-IgE-Mediated Food Allergy Among Pediatric Patients Diagnosed with Autism Spectrum Disorders Aimee Lou Manalo Nano A385 Component-Resolved Diagnostic Study of Dermatophagoides Pteronyssinus Major Allergen Molecules in a Southern China Wenting Luo, Baoqing Sun A386 Risk Factors for Systemic and Local Reactions to Subcutaneous Allergen Immunotherapy Hikmet Tekin Nacaroglu, Semiha Bahceci Erdem, Ozlem Sumer, Sait Karaman, Canan Sule Unsal Karkiner, Suna Asilsoy, Ilker Gunay, Demet Can A387 Literature Review and Current Treatment Options for Cyclical Anaphylaxis Danielle Kiers A388 The Effect of Surfactant Protein D in Acute Lung Injury and Pulmonary Fibrosis Induced By Bleomycin Hsu Han Yin, Jiu-Yao Wang A389 Activation of Endothelial Cells to Release Hsp90, an Activator of the Prekallikrein-High Molecular Weight Kininogen (HK) Complex Allen Kaplan, Kusumam Joseph, Baby G. Tholanikunnel A390 The Effect of Climatic Treatment in 51 Asthmatic Children from Areas Severely Polluted Environment of Northern Moravia, Czech Republic Radim Dudek A391 Comparison of Some Vitamin Groups in Asthmatic Patients Gulden Bilgin, Hatice Surer, Aytun Sadan Kilinc, Dogan Yucel A392 Sensitization in Children with Atopic Dermatitis: A Single Center Study Ji Young Lee, Jihyun Kim, Hea-Kyoung Yang, Minji Kim, Sang-Il Lee, Kangmo Ahn A393 Staphylococcal Enterotoxin IgE Sensitization: A Risk Factor for COPD Overlap in the Elderly Asthma? Sung Do Moon, Byung-Keun Kim, Sang-Heon Cho, Kyung-up Min, Yoon-Seok Chang, Heung Woo Park, Hye-Ryun Kang, Woo-Jung Song, Min-Koo Kang, Ju-Young Kim, Kyonghee Sohn, Ha Kyung Won, Seoung-Eun Lee, Kyung-Mook Kim, Claus Bachert A394 The Effects of Probiotics and PparÎ(3) on the Murine Model of Allergic Asthma Miao-Hsi Hsieh, Jiu-Yao Wang A395 Adult Patients’ Views on the Design of Adrenaline Autoinjectors Helen Smith, Clare Brown, Christina Jones, Mark Davies A396 CCL22 miRNA modulated Th1 responses and induced therapeutic effects on OVA-induced mouse model of asthma Won Suck Yoon A397 Clinical, Histological, and Skin Microbiome Characteristics of Head and Neck Dermatitis in Atopic Dermatitis Hemin Lee, Howard Chu, Jungsoo Lee, Jung U Shin, Chang Ook Park, Kwang Hoon Lee, Seo Hyeong Kim, Ji Yeon Noh, Ji Hye Kim A398 MicroRNA-432 modulates Th1 responses and induced therapeutic effects in atopic like murine model. Won Suck Yoon A399 Case Report of Near-Fatal Asthma Due to Snail Allergy in a House Dust Mite-Allergic Adult Jean-Pierre L’huillier, Jean-Eric Autegarden, Catherine Bertrand, Dominique Tardy A400 Relationship Between Gut Microbiota in the First 3 Months of Life and Infant Immune Function at Age 12 Months Intan Hakimah Ismail, Mimi Tang, Paul Licciardi, Frances Oppedisano, Robert Boyle, Roy Robins-Browne A401 A Pediatric Case of Food-Dependent Exercise-Induced Anaphylaxis Due to Spice Allergy Hisako Yagi, Harumi Koyama, Yutaka Nishida, Takumi Takizawa, Hirokazu Arakawa A402 Correlations Between Objective Severity Score and Each of the Subjective Severity Intensity in Atopic Dermatitis Hong Kyu Kang, Hemin Lee, Jungsoo Lee, Jung U Shin, Kwang Hoon Lee, Kwang Hoon Lee, Howard Chu, Chang Ook Park A403 Barrier Related Gene Mutations in Atopic Dermatitis Na Young Yoon, Hyeyoung Lee, Seong Jun Seo, Eunhee Choi, Hye-Young Wang, Minyoung Jung, Eung Ho Choi, Dong Hye Kim A404 Clinical Utility of Basophil Activation Test (BAT) in the Diagnosis of Drug Induced Anaphylaxis Joo-Hee KimYoung-Sook Jang, Jeong-Hee Choi, Sunghoon Park, Young Il Hwang, Seung Hun Jang, Ki-Suck Jung A405 Feeding Shapes the Colonization of Gut Microbiota and Associated with Total IgE in Infant Mi-Jin KangDongin Suh, Eun Lee, Kil Yong Choi, Young-Ho Jung, Song-I Yang, Bong-Soo Kim, Ha-Jung Kim, Juneyoung Koh, Hyun-Jin Kim, Kangmo Ahn, Youn Ho Shin, Hyun-Ju Cho, Byoung-Ju Kim, Young-Ho Kim, Yean Jung A406 CD8(+)T Cell-Intrinsic Smad4 Suppresses Th2 Responses in the Pathogenesis of Contact Hypersensitivity Mizuko Mamura, Jeong-Hwan Yoon, Susumu Nakae, Inkyu Lee, Isao Matsumoto, Takayuki Sumida, Jin Soo Han, Katsuko Sudo, Ji Hyeon Ju A407 Immune-Modulatory Genomic Properties Differentiate Gut Microbiotas of Infants with and without Eczema Gaik Chin Yap, Wen Tso Liu, Seungdae Oh, Pei Ying Hong, Chiung Hui Huang, Marion Aw, Lynette Shek, Bee Wah Lee A408 The Effect of Medication in OSA Patients with Allergic Rhinitis Young Seok Byun, Sung Wan Kim, Tae Kyung Koh, Joong-Saeng Jo, Kun Hee Lee, Chul Kwon, Sung-Hwa Dong A409 A Case of Generalized Pustular Psoriasis Mimicking Acute Generalized Exanthematous Pustulosis Myung Shin Kim, Chansun Park A410 Anaphylaxis Caused By Gummy Jelly Ingestion: A Case Report Han Seok Cho, Min-Ju Kim, Min Ji Kim, Young Ok Park, Hye Yeong Lee, Hee Seong Kim, Eun Lee, Hyun-Ju Cho, Jinho Yu, Soo-Jong Hong, Keum Hee Hwang A411 Serum Folliculin As a Novel Biomarker for Asthma Jung-Hyun Kim, You Sook Cho, Sae-Hoon Kim, Hyouk-Soo Kwon, Mira Yoo, Hyo-Jung Kim, So-Young Park, Bomi Shin, So Young Park, Bomi Seo, Min-Gu Kim, Hee-Bom Moon, Jin-Ah Park, Tae-Bum Kim, Jaemoon Lee A412 Corticosteroid Nasal Irrigations after Endoscopic Sinus Surgery in the Management of Chronic Rhinosinusitis with Asthma Jin Hyeok Jeong, Tae Wook Kang, Han Seok Yoo, Yong Hee Cho, Seok Hyun Cho, Kyung Rae Kim A413 Capsaicin Injection in Neonatal Period Potentiates Intensity and Duration of Atopic Dermatitis of Rats. Jue Seong Lee, Sun-Ho Kee, Sewon Kim, Young Yoo, Heung Sik Na, Seung Keun Back A414 Comparison Between the Impulse Oscillometry System, Spirometry, Feno, Lung Clearance Index and Asthma Control and Exacerbation Status. Seung Jin Lee, Bo Seon Seo, Ji Hyeon Baek, Kyung Suk Lee, Young-Ho Jung, Hye Mi Jee, Youn Ho Shin, Man Yong Han, Mi-Ae Kim A415 The Association of Exhaled Nitric Oxide and Airway Hyperresponsiveness in Patients with and without Asthma Young-Hee Nam, Dong Sub Jeon, Soo-Keol Lee A416 Effects of Air Pollution on Allergic Rhinitis in Korea Jisun Park A417 Exhaled Nitric Oxide in Korean Children with Allergic Rhinitis Seung Hyun Moon A418 A Questionnaire of Children with Asthma or Asthma and Allergic Rhinitis Rong Jun Lin, Ren Zheng Guan A419 A Case of Trimebutine-Induced Morbilliform Skin Eruption Gyeong Yul Park, Hyun-Sun Yoon A420 Comparison of Methacholine and Mannitol to Predict Exercise-Induced Bronchoconstriction in Children with Asthma Woo-Hyeok Choi, Heysung Baek A421 Different Inflammatory Mechanisms of Human Metapneumovirus and Respiratory Syncytial Virus Jin-Sung Park, Eunmi Kwon, Zac Callaway, Chang-Keun Kim, Takao Fujisawa A422 Sputum Microbiota in Chinese Adults with Eosinophilic Versus Non-Eosinophilic Asthma Qingling Zhang, Rihuang Qiu, Naijian Li, Zhaowei Yang, Jing Li, Kian Fan Chung, Nanshan Zhong A423 Which Clinical Features Are Useful in Predicting Presence of Staphylococcus Aureus colonization/Infection in Childhood Atopic Dermatitis? Kam Lun E. Hon, Yin Ching K. Tsang, Ting Fan Leung A424 Clinical Significance of Increased VEGF, TGF-Î(2)(1,) and YKL-40, a Chitinase like Protein, in Serum of the Children with Asthma Yoon Young Jang, Hai Lee Chung, Seung Gook Lee, Ji Hyun Na, Jong Hoon Lee A425 Analysis of Follow-up Results of Mannitol Challenge Test in Asthma Patients Young-Hee Nam, Dong Sub Jeon, Soo-Keol Lee A426 Analysis of 68 Oral Walnut Challenge Tests Mikita Yamamoto, Sakura Sato, Noriyuki Yanagida, Ayako Ogawa, Kanako Ogura, Kyohei Takahashi, Kenichi Nagakura, Shigehito Emura, Tomoyuki Asaumi, Katsuhito Iikura, Motohiro Ebisawa, Yu Okada A427 Effectiveness of Air Filters Intervention in Allergic Rhinitis Jiaying Luo, Xiao Lan, Baoqing Sun, Zhao Chen, Guiyuan Sun, Shimin Li, Jiaqing Hu A428 The Relationship Between Airway Hyperresponsiveness to Mannitol and Atopy in Asthmatic Children Woo-Hyeok Choi, Heysung Baek A429 Anaphylactoid Reactions to N-Acetylcysteine in the Treatment of Aacetaminophen Overdose Young-Hee Nam, Dong Sub Jeon, Hee-Joo Nam, Yeo Myeong Noh, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A430 Effect of Prenatal Maternal Distress and GSDMB Polymorphism on the Development of Recurrent Wheezing in Early Childhood: COCOA Study Yean Jung Choi, Si Hyeon Lee, Young-Ho Kim, Mi-Jin Kang, Hyun-Ju Cho, Eun Lee, Song-I Yang, Youn Ho Shin, Kangmo Ahn, Kyung Won Kim, Yoon Hee Kim, So-Yeon Lee, Hyoung Yoon Chang, In Ae Choi, Kyung-Sook Lee, Yee-Jin Shin A431 Vitamin D Level in Allergic Rhinitis: A Systemic Review and Meta-Analysis Yoon Hee Kim, Min Jung Kim, In Suk Sol, Seo Hee Yoon, Young a Park, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim, Yong Ju Lee A432 Implication of Inspiratory and Expiratory Resistance and Reactance in Children with Asthma In Suk Sol, Kyu-Earn Kim, Yoon Hee Kim, Min Jung Kim, Seo Hee Yoon, Yong Ju Lee, Kyung Won Kim, Young a Park, Myung Hyun Sohn A433 The Association of Asthma Predictive Index with Asthma in Preschool Children with Recurrent Wheeze Sung Joo Park, Ji-Won Kwon, Woo Kyung Kim, Hyung Young Kim, Hyo-Bin Kim, Ju-Hee Seo, So-Yeon Lee, Gwang-Cheon Jang, Young-Ho Jung, Soo-Jong Hong, Byoung-Ju Kim, Dae-Jin Song, Yun Seok Yang, Jung Yeon Shim A434 Clinical Significance of Serum Total IgE Levels in Children with RSV-Associated Lower Respiratory Illness Yoon Young Jang, Hai Lee Chung, Ji Hye Kim, Hyun Seok Lee, Chang Ho Lee A435 Development of a Oak Pollen Emission and Transport Modeling Framework in South Korea Changbum Cho, Yun-Kyu Lim, Kyu Rang Kim, Mijin Kim, Baek-Jo Kim A436 Temperature, Humidity, and Air Pollution Affect Atopic Dermatitis Symptoms in Infants and Young Children Young-Min Kim, Youngshin Han, Jihyun Kim, Hae-Kwan Cheong, Byoung-Hak Jeon, Kangmo Ahn A437 Effects of Compound V on Pulmonary Fibrosis Model Chuang/Yao Ming, Jiu-Yao Wang, Ye/Yi Ling A438 Vitamin D Level and the Correlation with IgE in Children with Allergic Respiratory Diseases in Guangzhou China Huimin Huang, Baoqing Sun, Yun Chen, Peiyan Zheng, Nili Wei, Wenting Luo A439 Two Case Reports of Eosinophilic Gastroenteritis Associated with Allergic Disease Do Hyeong Lee, Gil-Soon Choi, Hee-Kyoo Kim, Han Su Park A440 Genome-Wide Association Study (GWAS) May Identify Common Genetic Variations Both in Immediate and Delayed Drug So-Young Park, Hyo-Jung Kim, Bomi Seo, Jung-Hyun Kim, Min-Gu Kim, Hyouk-Soo Kwon, You Sook Cho, Hee-Bom Moon, Tae-Bum Kim, Yoon Su Lee A441 Development of a Questionnaire for Secular Change of Atopic Dermatitis from Birth to 19-Year-Old. Akio Tanaka, Satoshi Morioke, Yukihiro Ohya, Naoki Shimojo, Akira Akasawa, Michihiro Hide, Hiroko Shizukawa A442 Evaluation of the Adherence Starts with Knowledge-20 (ASK-20) to Inhaled Drug in Patients with Bronchial Asthma Naoto Watanabe A443 The Epidemiology and Clinical Manifestation of Hmpv Infection in Children during Recent 4 Years: 2011-2014 Meeyong Shin, Myeong Sun Jang A444 Neutropenia Induced By Intravenous Immunoglobulin Young-Hee Nam, Yeo Myeong Noh, Dong Sub Jeon, Hee-Joo Nam, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A445 A First Case of Lymphocytic Interstitial Pneumonitis in Healthy Child Ji-in Jung, Ha-Su Kim, Hyun-a Kim, Jin-a Jung A446 Cytokine Production upon House Dust Mite Stimulation of Cord Blood Mononuclear Cells from Caesarean Section-Delivered Singaporean Infants Anne Goh, Rajeshwar Rao, Bindu Nandanan, Ruurd Van Elburg, Chua Mei Chien, Juandy Jo, Johan Garssen, Johan Garssen, Leon Knippels, Elena Sandalova, Wen Chin Chiang A447 Dress Syndrome with Acute Interstitial Nephritis Caused By Quinolone and Nonsteroidal Anti-Inflammatory Drugs Young-Hee Nam, Ji Young Juong, Soo Jin Kim, Eun Young Kim, Su Mi Lee, Young Ki Son, Hee-Joo Nam, Ki-Ho Kim, Soo-Keol Lee A448 IL-23 Roles in the Development of House Dust Mite Allergic Sensitization and Asthma Da-Eun Park, Hye-Ryun Kang, Heung Woo Park, Hyun Seung Lee, Yoon-Seok Chang, Jung-Won Park, Sang-Heon Cho, Kyung-up Min, Woo-Jung Song A449 Exposure Profile of Indoor Risk Factors in Dwellings of Children with Atopic Dermatitis Hyunwook Lim, Sungchul Seo, Ji Tae Choung, Young Yoo, Jun-Sik Park, Byung Kwan Kim A450 Epidemiological Characterization of Blood Eosinophils in the Elderly Population Ha Kyeong Won, Hye-Ryun Kang, Byung-Keun Kim, Sung Do Moon, Ju-Young Kim, So-Hee Lee, Woo-Jung Song, Heung Woo Park, Min-Koo Kang, Sun-Sin Kim, Sang-Heon Cho, Kyung-up Min, Yoon-Seok Chang, Kyoung Hee Sohn, Kyung-Mook Kim, Ki-Woong Kim, Hak Chul Jang A451 Stevens-Johnson Syndrome Caused By Methotrexate in the Treatment of Psoriasis Young-Hee Nam, Dong Sub Jeon, Hee-Joo Nam, Yeo Myeong Noh, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A452 Genetic Determinants for Lung Function Growth in Asthmatic Children Ting Fan Leung, Man Fung Tang, Hing Yee Sy, Wa Cheong Chan, Wilson Wai San Tam A453 The Power of Allergen Specific Ig E in the Classification of Rhinitis, Korean National Hanes 2010 Seung Kyu Chung, Sujin Kim, Sang Duk Hong, Hyo Yeol Kim Hyo Yeol Kim, Hun-Jong Dhong, Jong in Jeong A454 Analysis of Allergen Immunotherapy Practice and Patients’ Knowledge and Attitude about Allergen Immunotherapy in a Single Tertiary Hospital in Korea Young-Hee Nam, Dong Sub Jeon, Soo-Keol Lee A455 Roles of Staphylococcal Enterotoxin B in House Dust Mite-Induced Acute Asthma Models Ji Won Lee, Mingyu Kang, Soon-Hee Kim A456 A Clinical Comparison of Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome in a Single Tertiary Hospital in Korea Young-Hee Nam, Dong Sub Jeon, Hee-Joo Nam, Yeo Myeong Noh, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A457 The Beneficial Effect of Lactobacillus Gasseri PM-A0005 and Its Immunoregulatory Protein PMA5P40 on Milk-Induced Allergic Enteritis Yung-I Hou, Jiu-Yao Wang A458 Relationship Between Serum Folate Levels and Risks of Allergic and Respiratory Diseases in Early Childhood: The Mothers and Children’s Environmental Health Study Ja Hyeong Kim, Seol Jae Hee, Eun-Hee Ha, Hyesook Park, Mina Ha, Yun-Chul Hong, Yangho Kim, Namsoo Chang A459 Effects of Vitamin D in Patients with Chronic Rhinosinusitis Yuta Soma, So Watanabe, Ruby Pawankar, Ruby Pawankar, Harumi Suzaki, Harumi Suzaki, Hitome Kobayashi A460 Clinical Features of Systemic Contact Dermatitis from Ingestion of Rhus Young-Hee Nam, Chansun Park, Soo-Keol Lee A461 Sublingual Immunotherapy Efficacy in Patients with Atopic Dermatitis in Korea Jongrok Lee, Jooyoung Roh, Haryeong Ryu A462 Characteristics of Serious Adverse Drug Reactions in a Tertiary University Hospital Cheol-Woo Kim, Jae Hwa Cho, Mi Ra Eom, Ji Young Kang, Hye Gyeung Lee A463 Eyelid Dermatitis: Patch Test Results during a 15-Year Period in Korea and Evaluation of Metal Contents in Eye Shadows Hae Young Choi, Hye Jin Lee, Ju Yun Woo, Ji Yeon Byun, You Won Choi A464 Relationship Between Lipid Levels and Risks of Allergic and Respiratory Diseases in Early Childhood: The Mothers and Children’s Environmental Health Study Ja Hyeong Kim, Eun-Hee Ha, Hyesook Park, Mina Ha, Yun-Chul Hong, Yangho Kim, Namsoo Chang A465 IL-32 in the Induced Sputum of Patients with Asthma Jae-Woo Kwon, Hun Soo Chang, Jeong-Seok Heo, Jong-Uk Lee, Jong-Sook Park, Eusom Kim, Soo Hyun Kim, Choon-Sik Park A466 Clinical Characteristics of Patients with Chromium Allergy in a Single University Hospital in Korea Hae Young Choi, Ji Yeon Byun, Ju Yun Woo, You Won Choi A467 Efficacy and Safety of Oral Acitretin in Chronic Hand Eczema Hyun-Ju Jin, Jin-Hwa Son, Jeong-Min Kim, Gun-Wook Kim, Je-Ho Mun, Margaret Song, Hyun-Chang Ko, Moon-Bum Kim, Hoon-Soo Kim, Byung Soo Kim A468 Atypical Antipsychotics and Anticholinergic Agents Mimicking Anaphylaxis Sheryl Van Nunen, Dinh Van Nguyen, Anthony Elias, Susannah Olivia Lauer A469 Introducing Reach (Reliable Estimation of Atopic dermatitis in ChildHood): Novel, Questionnaire-Based Diagnostic Criteria for Childhood Atopic Dermatitis Seung-Chul Lee, Ho-June Lee, Jung Min Bae A470 Comprehensive Assessment to Identify the Causative Factors in Oral Allergy Syndrome Emi Ono A471 Comparison of Interpretation Methods in Allergic Skin Test Sung-Hwa Dong, Tae Kyung Koh, Young Seok Byun, Sung Wan Kim, Joong-Saeng Jo, Chul Kwon, Kun Hee Lee A472 Refraining Aminophylline Use Increases Hospitalization Among Children with Acute Asthma: A 10-Years Retrospective Cohort Study Li-Fan Liu A473 The Prevalence and Risk Factors of Atopic Dermatitis from Nationwide Study for Korean School Students Sunghee Lee A474 Probiotic Recombination Protein Effect on Atopic Dermatitis Wei-Leng Chen, Jiu-Yao Wang A475 Allergic Sensitization Status in Various Inflammatory Skin Diseases Youin Bae, Gyeong-Hun Park A476 Two Cases of Good’s Syndrome: A Rare Acquired Immunodeficiency Associated with Thymoma Suk Yeon Kim A477 IL-23 Has a Role to Play in the Development of Asthma in Short-Term Cigarette Smoke Exposure-Induced House-Dust Mite Allergic Model Hyun Seung Lee, Woo-Jung Song, Mingyu Kang, Han-Ki Park, Da-Eun Park, Hye-Ryun Kang, Heung Woo Park, Yoon-Seok Chang, Hye-Young Kim, Kyung-up Min, Sang-Heon Cho, Ji-Won Lee, Boram Bae, Jung-Won Park A478 The Relationship Between the Relevance of Allergic Disease and the Value of Non-Specific IgE Yasuhiro Suzuki A479 Two Caces of Prawn Allergy in Adult Patients Ismet Bulut, Zeynep Ferhan Ozseker A480 Early Gut Bifidobacterium Breve and B. Catenulatum Colonisation Differentially Modulate Eczema Risk in Children at High-Risk of Developing Allergic Disease Intan Hakimah Ismail, Robert Boyle, Paul Licciardi, Frances Oppedisano, Roy Robins-Browne, Mimi Tang A481 Effects of Chronic Repeated Exposure of Staphylococcal Enterotoxin B on Allergic Asthma Model in Mice Ji Won Lee, Hyun Seung Lee, Mingyu Kang, Da-Eun Park, Han-Ki Park, Soon-Hee Kim, Woo-Jung Song, Hye-Ryun Kang, Heung Woo Park, Yoon-Seok Chang, Chang-Han Park, Suk-Il Chang, Sook-Hee Song, Kyung-up Min, Sang-Heon Cho, Boram Bae A482 Skin Prick Test Result and Allergen Immunotherapy in Children with Allergic Rhinitis Grace Shieh A483 Role of Brp-39 in RSV-Induced Airway Inflammation in Mice Min Jung Kim, Jung Yeon Hong, Seo Hee Yoon, Doo Hee Shim, In Suk Sol, Yoon Hee Kim, Mi Na Kim, Kyung Eun Lee, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim, Jae Myun Lee A484 Long-Term Outcomes of Twenty-Four Adults with Primary Immunodeficiency from a Single Centre in Singapore Hiok Hee Chng A485 Breast Feeding Increases the Risk of Food Sensitization but Does Not Affect Food Allergy in Young Children with Atopic Dermatitis Dong Chan Kim, Song-I Yang, Hae Ran Lee, An Deok Seo, So Yeon Lee A486 IgE Immunoadsorption Knocks Down Anaphylaxis. Alessandro Fiocchi, Maria Cristina Artesani, Paola Francalanci, Lamia Dahdah, Thomas Schreiner A487 Burden and Correlates of Cigarette Smoking and Respiratory Airway Obstruction: An Observation in Urban Adult Population of West Bengal (India) Kaushik Chakraborty A488 Blood Eosinophils Could Predict Sputum Eosinophilia? : A Comparison Between Asthma and Non-Asthmatic Chronic Cough in the Elderly Ha Kyeong Won, Ju-Young Kim, Eun-Jung Jo, Kyoung Hee Sohn, Kyung-Mook Kim, Heung Woo Park, Yoon-Seok Chang, Sang-Heon Cho, Woo-Jung Song, Byung-Keun Kim A489 Complementary and Alternative Medicine for Allergic Rhinitis in Japan Syuji Yonekura, Yoshitaka Okamoto A490 Impact of Cognitive Impairment on Asthma Control Status in Elderly Asthmatics Gyu Young Hur, Young Min Ye, Joo-Hee Kim, Ki-Suck Jung, Junga Kim, Jae Jeong Shim, Hae-Sim Park A491 The Association Between Respiratory Tract Infection and Reactive Oxygen Stress Kazuhiro Sekimoto, Kazuko Sugai, Keiji Tsuchimoto, Hiromi Uehara, Masanori Ikeda A492 The Risk Factors and Lung Function of Current Allergic Rhinitis Due to Dust Mite Sensitization Euncho Chung, Kang Seo Park, Yean Jung Choi, Jeewon Park, Soo-Jong Hong, So Yeon Lee A493 Cloning and Expression of Recombinant Blomia Tropicalis Dust Mite Allergen Blo t 7 Alain Jacquet, Arun Buaklin, Nat Malainual A494 Seasonal Variations of Airborne Pollen in Bangalore, India Roopashree S A495 Pollen Observation and Use of Data Kyu Rang Kim, Mijin Kim, Changbum Cho, Baek-Jo Kim, Jae-Won Oh, Mae Ja Han A496 The Effect of Cord Serum 25-Hydroxyvitamin D (25(OH)D) on the Development of Atopic Dermatitis in First 3 Years of Life : Cocoa Study Hyun-Ju Cho, Youn Ho Shin, Eun Lee, Young-Ho Kim, Darae Lee, Mi-Jin Kang, Song-I Yang, Kangmo Ahn, Kyung Won Kim, Yoon Hee Kim, Hye-Sung Won, Soo Hyun Kim, Suk-Joo Choi, Young Han Kim, Jong Kwan Jun, Eun-Jin Kim, Jeom Gyu Lee, So-Yeon Lee, Soo-Jong Hong, Dongin Suh A497 Contribution of Stem Cell Factor Autocrine/Paracrine Mechanism to Aberrant Proliferation of Mast Cells Yosuke Amagai, Akane Tanaka, Hiroshi Matsuda A498 A Randomized Dbpc Dose-Finding Multicenter Trial of Sublingual Immunotherapy (SLIT) Allergoid Tablets in House Dust Mites (HDM) Allergic Patients Ralph Mösges, Pauline Dieterich, Anatoli Astvatsatourov, Christoph Hüser, Jaswinder Singh, Kija Shah-Hosseini, Silke Allekotte, Enrico Compalati A499 Depression and Allergy in the Elderly: A Community Population Analysis Kyoung Hee Sohn, Woo-Jung Song, Byung-Keun Kim, Ju-Young Kim, Min Suk Yang, So-Hee Lee, Sae-Hoon Kim, Hye-Ryun Kang, Heung Woo Park, Sun-Sin Kim, Kyung-up Min, Sang-Heon Cho, Yoon-Seok Chang A500 The Integrated Analysis of Correlation Between Total IgE and Other Immunological Factors in Allergic Diseases Woo-Sung Chang, Ji-Hye Do, Yeon-Seop Kim, Dankyu Yoon, Hye-Sun Lim, Jeom-Kyu Lee, Eun-Jin Kim A501 Pattern of Allergic Diseases Among Military Servicemen Referred to a Clinical Immunology/Allergy Service in Singapore Bernard Thong, Yew Kuang Cheng, Jinfeng Hou, Khai Pang Leong, Justina Tan, Faith Chia, Grace Chan, Sze-Chin Tan, Teck Choon Tan, Chwee Ying Tang, Hiok Hee Chng A502 A Case of Rifampicin-Induced Hypersensitivity Diagnosed By the Lymphocyte Activation Test with Successful Desensitization Chan-Sun Park, Mi Yeoung Kim, Eun-Young Kim, Jae-Gook Shin, Jae-Hyeog Choi, Saegwang Park, Yeonye Kim A503 Analysis of Individual Case Safety Reports of Drug-Induced Anaphylaxis Based on Korea Adverse Event Reporting System Database Kyung-Hwan Lim, Jae Woo Jung, Mingyu Kang, Ju-Young Kim, Ju-Young Kim, Hyun Jeong Kim, Yeon-Ju Woo, Soo-Youn Jung, Hye-Ryun Kang, Hye-Ryun Kang A504 Impact of Processes Certification on the Liability of Anti-Dust Mites Bed Covers Thierry Porée, Nabile Boukhettala, Emeline Furon A505 Localisation Kinetics of Aluminium after Subcutaneous Injection in a Rat Model Alan David Bullimore, Matthew Heath, Simon Hewings, Murray Skinner A506 Periostin Levels in Exhaled Breath Condensate of Competitive Athletes, Asthmatics and Healthy Subjects - Associations with Outdoor Ambient Conditions Marcin Kurowski, Hubert Krysztofiak, Aleksandra Wardzynska, Marzanna Jarzebska, Janusz Jurczyk, Marek L. Kowalski A507 The Role of PKR Pathway in Acute Exacerbation of Severe Bronchial Asthma So Ri Kim, Yong Chul Lee, Dong Im Kim, Yang Keun Rhee, Heung Bum Lee, Seoung Ju Park, Yeong Hun Choe Choe, Seung Yong Park A508 Diversity of Clinical Manifestations and Treatment Responses for Idiopathic Hypereosinophilic Syndrome Joo-Hee Kim, Sunghoon Park, Young Il Hwang, Seung Hun Jang, Ki-Suck Jung A509 Effect of Dexamethasone in Th17 Cell Mediating Neutrophilic Asthma Nong Guang-Min, Jiang Min A510 Allergen Profile for Asthma/Rhinitis and Eczema Among Patients in North India: An Immunocap Allergen Specific IgE Antibodies Assay Based Study Nalin Nag A511 Clinical Profile of Allergic Rhinitis in Children in Jakarta Wahyuni Indawati A512 Preclinical Study on the Use of Micro Crystalline Tyrosine (MCT) Adjuvants in Allergy Immunotherapy Alan David Bullimore, Matthew Heath, Murray Skinner A513 Genetic Diversity of Filaggrin Mutation and Its Clinical Implication in East Asian Atopic Dermatitis Patients Seong Jun Seo, Won Jong Oh A514 Protein and MPL Adsorption Capacities for MCT in Candidate Therapeutic Formulations for Use in Immunotherapy, Compared Against Existing Adjuvants Alan David Bullimore, Murray Skinner, Matthew Heath, Andrew Bell A515 Interleukin-22 Gene Variation in Inflammatory Bowel Disease Alireza Zarebidoki, Hournaz Hasanzadeh, Salman Sadeghzade, Nima Rezaei A516 Immunomodulatory Effects of Adipose-Derived Stem Cell Secretome in a Mouse Model of Asthma Kyu-Sup Cho A517 Diffuse Alveolar Hemorrhage with Positive Anti-Neutrophil Cytoplasmic Antibody in a Child : A Case Report Sung-Woo Kim, Moo-Young Oh A518 Clinical Analys the Serum TARC Levels As the Condition Index of Atopic Dermatitis in the Early Infancy Munemitsu Koizumi, Kazuyo Kuzume A519 An Analysis of the Filaggrin Gene Polymorphism in Korean Atopic Dermatitis Patients Kui Young Park, Won Jong Oh A520 A New Protocol for Wheat Oral Immunotherapy in Patients with Anaphylaxis Delara Babaie, Mohammad Nabavi, Fariborz Zandieh, Mehrdad Amir Moini, Zahra Chavoshzadeh, Hamideh Seifi, Mitra Sahragard, Mehrnaz Mesdaghi, Mohammad Hassan Bemanian A521 Clinical Characteristics of Filaggrin-Related Atopic Dermatitis Patients in Korea Sun Young Choi, Yeon a No A522 Early Allergy Diagnosis in Children - Self- Administered Questionnaire Vs Medical Verification Andrzej M. Fal, Dorota Kiedik, Agnieszka Muszynska, Iwona Pirogowicz A523 Asthma Impact on Children with Food Induced Anaphylaxis Chikako Motomura, Masatoshi Wakatsuki, Yuko Akamine, Mihoko Iwata, Hiroshi Matsuzaki, Naohiko Taba, Yoko Murakami, Hiroshi Odajima A524 Case Reports of Stevens-Johnson Syndrome and Stevens-Johnson Syndrome-Toxic Epidermal Necrolysis in Systemic Lupus Erythematosus Reni Ghrahani A525 The Effectiveness of Oral Tolerance Induction for Wheat Allergy Using Two Different Intake Levels Yuri Takaoka A526 Association of Plasma Interleukin-25 Levels with Development of Aspirin Induced Airway Spasm in Asthma Jong-Uk Lee, Jeong-Seok Heo, Da-Jeong Bae, Hyun Ji Song, Choon-Sik Park, Jong-Sook Park A527 Transition of Allergic and Nonallergic Rhinitis after 2 Years in Korean Children: Preliminary Study Jae Hoon Cho, Ji Ho Choi A528 Early Onset of Psoriasis Juvenile Idiopathic Arthritis Budi Setiabudiawan, Fiska Febriana, Reni Ghrahani, Gartika Sapartini A529 Clinical Features of Immediate Hypersensitivity to Histamine H2 Antagonists and Their Cross Reactivity Chan-Sun Park, Young-Hee Nam, Mi Yeoung Kim, Gil-Soon Choi A530 Detection of Galacto-Oligosaccharide Specific IgE in Vitro Chiung-Hui Huang, Chiung-Hui Huang, Jian Yi Soh, Lynette Shek, Lynette Shek, Dianne J. Delsing, Bee Wah Lee, Bee Wah Lee, Si Hui Goh, Wen Chin Chiang, Wenyin Loh A531 The Association Between Serum Vitamin D Levels and Allergic Diseases in Elementary Schoolchildren Hea-Kyoung Yang, Ji Young Lee, Minji Kim, Kangmo Ahn, Jihyun Kim, Young-Min Kim, Hye-Young Kim, Yong Mean Park, Woo Kyung KIM, So-Yeon Lee A532 Serum Levels Specific IgE to Toxic Shock Syndrome Toxin Type 1 in Eosinophilic Chronic Rhinosinusitis with Nasal Polyp in Korean Jongin Jeong, Sang Duk Hong, Seung Kyu Chung, Hun-Jong Dhong, Hyo Yeol Kim Hyo Yeol Kim, Sujin KIM A533 Impacts of Rhizosphere Cleaning Effects of Potted Indoor Plants on the Symptoms and Stress of Students with Allergic Rhinitis in Newly Built Schools Yong-Won Lee, Hana Bak, Hye-Rim Son, Si-Eun Lee, Kwang-Jin Kim, Young-Wook Lim, Ho-Hyun Kim A534 A Case of Multiple Food Allergies with Recurrent Anaphylaxis Successively Controlled By Omalizumab Mi-Ae Kim, Man Yong Han, Young-Ho Jung, Hye Mi Jee, Seung Jin Lee, Kyung Suk Lee A535 Bepotastine-Induced Urticaria, Cross-Reactive with Other Antihistamines Jasmina Golez, Jaechun Lee, Eunkyoung Lee A536 Role of SLC26a4 in Ozone - Induced Airway Reactivity and Inflammation Da-Jeong Bae, Chang-Gi Min, Jong-Uk Lee, Jong-Sook Park, Hun Soo Chang, Choon-Sik Park, An-Soo Jang A537 PAR2-Antagonist Suppresses Protease-Induced Allergic Inflammation Mediated By Degradation of Lung Epithelial Tight Junction and Generation of ROS Young-Joon Kim, Bok Kyoung Jung, Seung-Hwa Lee, Mi-Jin Kang, Sekyoo Jeong, Eun Lee, Hyun-Ju Cho, Young-Ho Kim, Song-I Yang, Seo Hee Kim, Soo-Jong Hong A538 Novel Anti-IL-4Ra Nanocarrier Approach for the Efficient Control of Lung Tissue Inflammation during Asthma Rabih Halwani, Saleh Al Muhsen, Asma Sultana, Achraf Al-Faraj, Rosan Kanana, Sibtain Afzal, Roaa Al Kufaidi A539 Clinical Factors for Improved Allergen Reactivities Induced By Subcutaneous Allergen Specific Immunotherapy with House Dust Mites during 1 Year Period Hee-Kyoo Kim, Chul-Ho Oak, Gil-Soon Choi, Ye-Jin Moon, Eun-Kee Park A540 Cytokine Gene Polymorphisms in Iranian Patients with Kidney Acute Rejection Alireza Zarebidoki, Mina Abrari, Ali Akbar Amirzargar A541 Phthalate Exposure and Obesity in Atopic Dermatitis of Korean Children and Adolescents Ju-Hee Seo, Mina Ha, Soo-Jong Hong A542 Which Drives Chronicity of Cough in Adults: Based on the Knhanes 2010-2012 Mingyu Kang, Byung-Ha Cho, Han-Ki Park, Han-Ki Park, Kyung-Mook Kim, Chang-Han Park, Heung Woo Park, Heung Woo Park, Yoon-Seok Chang, Yoon-Seok Chang, Yoon-Seok Chang, Sook-Hee Song, Mi-Kyeong Kim, Mi-Kyeong Kim, Sang-Heon Cho, Suk-Il Chang, Kyung-up Min, Kyung-up Min, Alyn Morice A543 Elevated Airway CD45RO Memory Cells in Wheezing Children with Lower Respiratory Infection Jungi Choi, Yusok Han, Jin-Sung Park, Eunmi Kwon, Chang-Keun Kim A544 Quality of Life in Obese Children with or without Atopic Disease Gartika Sapartini A545 Relation of Human microRNA in Sputum of Asthma with Influenza A Virus Infection-Induced Exacerbation Ji-Na Kim, Seungwoo Shin, Hun Soo Chang, Eun-Young Shim, Ji Ah Jun, Hyeonju Lee, Jong-Sook Park, Choon-Sik Park A546 Aeropolinologic Monitoring and Distribution of Allergoallergens in Western Georgia Revaz Sepiashvili, Darejan Khachapuridze, Sofio Gamkrelidze, Manana Chikhladze A547 Extracorporeal Membrane Oxygenation As Emergency Treatment for Patients with Near-Fatal Status Asthmaticus Seung-Eun Lee, Yun-Seong Kim, Doo-Soo Jeon, Woo-Hyun Cho, Hye-Ju Yeo, Seong-Hoon Yoon, Seung-Hyun Kim A548 Relationship of S100calcium Binding Protein A9 with Neutophilic Inflammation in Murine Asthma Model Taehyeong Lee, Hyun Ji Song, Choon-Sik Park, Ji Ah Jun, Jong-Sook Park A549 Whole-Exome Sequencing of Aatopic Dermatitis in Korean Childhood Dankyu Yoon, Yeon-Seop Kim, Woo-Sung Chang, Mi-Jin Kang, Soo-Jong Hong, Jeom-Kyu Lee, Eun-Jin Kim A550 A Case of Generalized Molluscum Contagiosum in an Adult Patient with Severe Atopic Dermatitis Minkee Park A551 Discovery of Putative Macadamia Nut Allergens By Patient IgE Binding and a Label-Free Shotgun Proteomics Approach Nanju Alice Lee, Johanna Rost, Sridevi Muralidharan, Dianne Campbell, Sam Mehr A552 Anti-FcÎμri Antibody Inhibits Allergic March in Mice By Suppressing Th17 Pathway Via Suppression of FcÎμri-Mediated Mast Cells Activation Seung-Hwa Lee, Seon-Joo Yoon, Ha-Jung Kim, Eun Lee, Song-I Yang, Young-Ho Jung, Ho-Sung Yu, Hee-Suk Kim, Yeon Hee Park, So-Yeon Lee, Jun-Sung Park A553 Clinical Characteristics and the Associated Factors of ATG Hypersensitivity Reaction Ha Kyeong Won, Min-Koo Kang, Sung Do Moon, Byung-Keun Kim, Ju-Young Kim, Sang-Heon Cho, Hye-Ryun Kang, Ji-Su Shim, Soo Jie Chung A554 Reference Value and Utility of Total Serum Immunoglobulin E in Korean Schoolchildren Jaehee Choi, Kangmo Ahn, Kwanghoon Kim, Jihyun Kim, Jiyoung Lee A555 Two-Step Prescreening Skin Testing May be Useful for Reducing Immediate Hypersensitivity Reaction to Nonionic Contrast Media: Results of 7-Year Period in a Secondary Hospital Bo Bae Park, In Young Nho, Chang-Han Park, Jang Min Kim, Suk-Il Chang A556 Prevalence of Allergic Sensitization in Patients with Allergy Rhinitis; Gwangju, Jeonnam State Study Sun Kyung Kim, Hyung Chae Yang, Kwang Il Nam A557 Analysis of IgE Binding Components of Walnut in Korean Children Effect of Cooking Methods on the Allergenicity of Walnut Proteins Jeongmin Lee, Jeongmin Lee, Sooyoung Lee, Kyunguk Jeong, Se-Ah Jeon A558 Assessment of Autonomic Nervous Function in Subjects with Cholinergic Urticaria Associated with Acquired Idiopathic Generalized Anhidrosis Midori Fujiwara, Shoko Shindo, Hiroyuki Murota, Mayuko Tahara, Aya Takahashi, Ichiro Katayama A559 Interleukin 1 Beta in Sputum of Patients with Asthma: Relation with Airway Obstruction and Neutrophilc Inflammation Jae Woo Jung, Hyun Ji Song, Taehyeong Lee, An-Soo Jang, Jong-Sook Park, Hun Soo Chang, Choon-Sik Park, Byoung Whui Choi A560 Interleukin 8 in Sputum of Patients with Asthma: Relation with Neutrophilc Inflammation and Exacerbation Min-Hye Kim, Da-Jeong Bae, Hyun Ji Song, Taehyeong Lee, Ji Ah Jun, Jong-Sook Park, An-Soo Jang, Hun Soo Chang, Young Joo Cho, Choon-Sik Park A561 Prostaglandin E2 and Transforming Growth Factor-Î(2) Play a Critical Role in Suppression of Allergic Airway Inflammation By Adipose-Derived Stem Cells Sue Jean Mun A562 Inhalation of Fine Particles Kill Alveolar Macrophages to Release IL-1alpha That Promote Inducible Bronchus-Associated Lymphoid Tissue (iBALT) Formation Etsushi Kuroda, Koji Ozasa, Ken Ishii A563 Association Between Smoking and Allergic Diseases in the Korean Adult General Population Sunmi Kim, Gyeong-Hun Park A564 Relationship of S100 Calcium Binding Protein A9 with Inflammasome Activation in Murine Asthma Model Hyun Ji Song, Taehyeong Lee, Ji Ah Jun, Hun Soo Chang, Jong-Sook Park, Choon-Sik Park A565 Cluster Analysis of Asthma Phenotypes to Predict Exacerbation in Korean Population Mi-Ae Kim, Seungwoo Shin, Jong-Sook Park, Hun Soo Chang, You Sook Cho, Hae-Sim Park, Choon-Sik Park A566 Effect of AG490 on the Expression of TH17 CELLS and Tregs in the MOUSE MODEL of Neutrophilic Asthma Zhang Min A567 Association Between the Clinical Characteristics and Disease Severity in Hospitalized Bronchiolitis Patients Younger Than Two Years Old Seo Hee Yoon, In Suk Sol, Young a Park, Yoon Hee Kim, Min Jung Kim, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim A568 Comparison Between House Dust Mite and Aspergillosis Sensitization in Patients with High Level of Tige Wu Shiquan A569 The Prevalence of Metal Allergy in the Patients with Orthodontic Appliance Yongwon Lee, Hana Bak A570 Component Resolved Diagnosis and Single Nucleotide Polymorphism Analyses: Towards the Development of Specific Immunotherapy for Allergy Maricar Wisco Ching, John Donnie Ramos A571 Clinical Features of Anaphylaxis Caused By Peanut, Tree Nuts and Seeds in Children and Adolescents: Multi-Center Study with 126 Patients Kyunguk Jeong, Sooyoung Lee, Kangmo Ahn, Myung Hyun Sohn, Kyung Won Kim, So-Yeon Lee, Tae Won Song, Youhoon Jeon, Jihyun Kim, Taek Ki Min, Kyu-Earn Kim, Bok-Yang Pyun, Hyeon-Jong Yang, Hae Ran Lee, Youngmin Ahn, Ji-Won Kwon, Dae Hyun Lim, Jeong Hee Kim, Dongin Suh, Hyung Young Ki A572 A Report of Two Cases of Anaphylaxis Caused By Perilla Seed in Children Kyunguk Jeong, Byeong Sub Park, Sooyoung Lee, Se-Ah Jeon, Kyu Jung Park A573 Prenatal Fine Particulate Matter Affects Wheezing in Children with TLR4 Polymorphism: Cocoa Study Song-I Yang, Eun Lee, Hyun-Ju Cho, Young-Ho Kim, Mi-Jin Kang, Yean Jung Choi, Kil Yong Choi, Youn Ho Shin, Kangmo Ahn, Kyung Won Kim, Byoung-Ju Kim, So-Yeon Lee, Eun-Jin K A574 Intensified B Lymphocyte Depletion (IBLD) without Immunosuppressive Maintenance Treatment As a Rescue Therapy in Refractory Lupus Nephritis (LN): a 4-Year Observation. Roccatello Dario A575 Relationship Between Th17 Cells and Neutrophilic Airway Inflammation in Childhood Neutrophilic Asthma Jing Liao A576 Clinical Applications of Impulse Oscillometry in Asthma Management after Exacerbation in Preschool Children Yong Feng, Yunxiao Shang A577 Contact Allergy to Sodium Sulfite and Its Relationship to Facial Cosmetic Contact Dermatitis Yongwon Lee, Hana Bak A578 Effect of Exposure to Air Pollution on Asthma and Lung Function Development Hyung Young Kim, Byoung-Ju Kim, Ji-Won Kwon, Ju-Hee Seo, Eun Lee, So-Yeon Lee, Song-I Yang, Young-Ho Jung, Hyo-Bin Kim, Ho-Jang Kwon, Hee Ju Park A579 Role and Relational Mechanism of AG490 in Airwayinflammation in the Mouse Model of Neutrophilic Asthma Zhang Min, Nong Guang-Min, Jiang Min A580 Incidence of Adverse Reaction to Radioconstrast Media in a Single Tertiary Hospital Gyu Young Hur, Eun Jung Sim, Sora Yoon, Juwhan Choi, Junga Kim, Jae Keom Sim, Jee Youn Oh A581 Cow’s Milk Oral Food Challenge: Clinical and Laboratory Features in Korean Children Kyunguk Jeong, Byeong Sub Park, Jeong-Min Lee, Sooyoung Lee, Eunjae Cheon, Youngjoo Na, Kyu Jung Park, Eunjoo Lee A582 Validation of the Red Maple Trials Allergen Challenge Theatre for Ragweed Pollen Challenge William Yang, Suzanne Kelly, Rob Perrins, Jimmy Yang A583 Preliminary Evaluation of the Red Maple Trials Allergen Challenge Theatre for Grass Pollen William Yang, Suzanne Kelly, Rob Perrins, Jacob Karsh, Jimmy Yang A584 The Association Between Tobacco and the Risk of Asthma in Urban and Rural Children in San Francisco, Argentina Hector Badellino, Alvaro Teijeiro, Mabel Cuello, Marilyn Urrutia Pereira, Gustavo Egues A585 The Prevalence of Allergic Rhinitis in University Students in Manisa Ayse Aktas A586 Allergen Sensitization in Zimbabwean Children with Atopic Dermatitis Jin-Kyong Chun, Hilda Angela Mujuru, Elopy N Sibanda A587 Vitamin D Insufficiency in Asthmatic Patients Andreea Ioana Popescu, Raluca Greblescu A588 The Prevalence of Hypersensitivity Reactions Against Drugs Among University Students. Suheyla Rahman, Ayse Aktas A589 Sublingual Immunotherapy Among Problematic Patients, Suffering from Allergic Rhinitis. Nataly Tataurshchikova A590 A Novel Biomarker for Wheezing and Atopy in Early Infancy Eishika Dissanayake, Yuzaburo Inoue, Naoki Shimojo, Taiji Nakano A591 Prognostic Factors for Atopic Dermatitis in Spontaneously Born Babies from Low Socioeconomic Background Conny Tanjung A592 Higher IgE Antibody Levels Mediate Anti-Cancer Immunity in Transgenic KN1 Hyper-IgE Mice Erika Jensen-Jarolim, Judit Fazekas, Josef Singer, Anna Lukschal, Reinhard Horvat, Gertrude Achatz-Straussberger, Gernot Achatz A593 Fructooligosaccharides Intake during Pregnancy and Lactation Increases Gut Bifidobacterium and IL-27 in Breast Milk Yuji Fujita, Shuji Ikegami, Yoshitaka Nakamura, Yuzaburo Inoue, Naoki Shimojo, Yoichi Kohno, Shuichi Suzuki, Naoko Ozawa, Takayuki Kubota, Ken Nonaka, Osamu Ohara, Kentaro Masuda A594 Effect of Nintedanib on Asthma in Mouse Model Chin Kook Rhee, Sook Young Lee, Hwa Young Lee, Hea Yon Lee, Ji Young Kang, Sei Won Kim, Soon Seog Kwon, Young Kyoon Kim A595 Delayed Contrast Media Hypersensitivity after Coronary Angiography Gun-Woo Kim, Ju-Young Kim, Sang-Heon Cho, Hye-Ryun Kang, Hyo-Soo Kim, Jung Gyu Han, Jin Lee, Ji Young Lee, Ji Young Go, So Jung Park A596 Gene Expression Profiling in Patients with Chronic Idiopathic Urticaria Reveals Unique Gene Signature Distinct from Healthy Controls Julie Kim-Chang, Cassandra Love, Patricia Lugar A597 Failure to Recognize Lymphopenia in Newborn Leads to Undetectable Primary Immunodeficiency Endah Citraresmi A598 The Concordance Between Lung Function Test and Indonesian Version of Childhood Asthma Control Test (CACT) Nastiti Kaswandani, Cynthia Utami, Mardjanis Said A599 Synergistic Interaction Between Bronchiolitis and PM(10) Is Modified By IL-13 Polymorphism on Asthma Development: Replication from Cheer Study Young-Ho Jung, Song-I Yang, Byoung-Ju Kim, Ji-Won Kwon, Hwan-Cheol Kim, Jong-Han Leem, Ju-Hee Seo, Hyung Young Kim, So-Yeon Lee, Ho-Jang Kwon, Hyo-Bin Kim, Hyun-Ju Cho A600 The Transcription Factor Ehf Is Involved in TGF-b-Induced Suppression of Fceri and c-Kit Expression and Fceri-Mediated Activation in Mast Cells Susumu Yamazaki, Nobuhiro Nakano, Asuka Honjoh, Eisuke Inage, Yosuke Baba, Yoshikazu Ohtsuka, Toshiaki Shimizu A601 The Follow up of the Potential Immunosuppressant Effects of Marijuana (MJA) Ishaq M, Sameera MI Khan, Imran Khan, Sabeen Khan A602 Risk Factors of Allergen Sensitization at 3 Years: Results from the Gusto Study Evelyn Xiu Ling Loo, Anne Goh, Oon Hoe Teoh, Yiong Huak Chan, Seang Mei Saw, Kenneth Kwek, Peter D Gluckman, Keith M Godfrey, Hugo Van Bever, Yap Seng Chong, Bee Wah Lee, Lynette Shek, Alison Joanne Lee A603 IL-6 Blockade As a Steroid-Sparing Treatment for Rhupus Patients Daniela Rossi A604 Examination of Late Pulmonary Toxicity in Children Treated for Malignancies Agnes Nemeth A605 Technical Validation of the Repurposing of a Personal Particle Sampler to Determine House Dust Mite Exposure in the Ambient Air Torsten Sehlinger, Karl-Christian Bergmann, Frank Goergen A606 Zinc Deficiency in Children with Severe Atopic Dermatitis: More Common Than Generally Thought Mohammad S. Ehlayel, Abdul Bari Bener A607 Strong Association Between HLA-B*5801 Allele and Allopurinol – Induced Severe Cutaneous Adverse Reactions in Vietnamese Hieu Chi Chu, Nga Thi Quynh Do, Dinh Van Nguyen, Ha Thi Thu Nguyen, Huong Thi Minh Le, Sheryl Van Nunen, Christopher Vidal, Suran Fernando A608 Successful Rapid Desensitization to Glatiramer Acetate: Report of 2 Cases Fotis Psarros, Ekaterini Syrigou, Ekaterini Politi, Spyridon Chrysoulakis A609 Asthma Exacerbations Seasonal Variation in Two Perennial Phenotypes during Twenty Years (1995-2014): House Dust Mite Monosensitized and Non Atopic Patients Dimitrios Vourdas, Konstantinos Petalas A610 Occupational Allergy to Fungal Spores Among the Farmers of Paddy Fields in West Bengal, India: An Aeromycological and Immunological Approach Mouli SAHA, Kashinath Bhattacharya A611 Study of Efficacy of Sublingual Immunotherapy (SLIT) in Cases of Severe Persistent Allergic Rhinitis Subir Jain A612 Mesenchymal Stem Cells Suppress Lung Inflammation and Airway Remodeling in Chronic Asthma Rat Model Via PI3K/Akt Signaling Pathway Mesenchymal Stem Cells Suppress Lung Inflammation and Airway Remodeling in Chronic Asthma Rat Model Via PI3K/Akt Signaling Xiaolian Song, Haiyan Lin A613 Development of Allergen ELISA Kits for Dust Mites, Pollen, and Pet Dander Kyohei Nishikawa, Takashi Shimada, Hiroshi Yasueda, Tadao Enomoto, Daisuke Aizawa, Takayoshi Kobayashi A614 Yoga As a Lifestyle Modification to Improve the Quality of Life in Smokers with Allergic Rhinitis Chellaa R A615 Study of Incidence of Severe Persistent Allergic Rhinitis in Different Age Groups,Sex Prevalance and Type of Allergen” Aeroallergen or Food Allergen” Responsible for Severe Persistent Allergic Rhinitis in Central India Subir Jain A616 Causative Allergens in Cases of Severe Persistent Allergic Rhinitis in Central India Subir Jain A617 Atopic Dermatitis: A New Data on the Mechanisms of Chronic Pruritus Marina Yudina A618 The Efficacy and Safety of Peanut Oral Immunotherapy in High-Dose with Predicting Factors Ishaq M, Sameera MI Khan, Imran Khan, Sabeen Khan A619 Evaluation of Long-Term Prognosis and Topical Corticosteroid Usage after One Year of Proactive Treatment for Children with Moderate-to-Severe Atopic Dermatitis Mayako Saito A620 Allergy Symptoms in the First Two Months of Life Nurul Iman Nilam Sari A621 Factors Related to the Seasonal Variation of Allergic Rhinitis Jae Young Kim, Jaechul Song, Inah Kim, Kyeong Joon Lee, Soo Jin Park, Soo Yong Roh A622 Allergic Risk Survey in Lao Children at out-Patient Department, Children’s Hospital, Vientiane Capital, Lao PDR Somxay Billamay A623 Correlation Between Food Allergy, Aeroinhalant Allergy, Allergic Rhinitis, Atopic Dermatitis, and Acute Upper Respiratory Tract Infections and Levels of Severity of Asthma in Pediatric Medicine Department Saiful Anwar Hospital Indonesia Muchammad Fahrul Udin A624 Comparative Study of Pine, Oak, and Ginkgo Pollen Counts in Korea during Last Four Years Mae Ja Han, Jae-Won Oh, Kyu Rang Kim, Baek-Jo Kim A625 Effectiveness of Allergy-Test Directed Elimination Diets in Eosinophilic Esophagitis Jorge A Mazza, Jason Kangeun Ko, David JT Huang A626 Comparison of Cut-Off Values and Probability Curves for Egg Specific IgE in Diagnosis of Egg Allergy in Young Children Kanae Furuya, Keigo Kainuma, Takahiro Ito, Mizuho Nagao, Takao Fujisawa, Junya Hirayama, Yu Kuwahara A627 A Case of Persistent Atopic Dermatitis Associated with Parasitic Infection Rosanna Qualizza, Cristoforo Incorvaia, Anna Maraschini A628 Aeroallergenic Profile of Indoor Allergens and Their Clinical Relevance in Allergy and Asthma Patients in Saudi Arabia Syed Mohammed Hasnain, Abdulrahman Al-Frayh A629 Oral Exposure to the Amino Acid Glycine Inhibits the Onset of Allergic Disorders Anita Hartog, Jacqueline Bastiaans, Reinilde Loonstra, Lieke Rutten, Lucien Harthoorn, Jeroen Van Bergenhenegouwen, Johan Garssen, Johan Garssen A630 Cough As a Key Symptom in Asthma, Allergic Rhinitis, COPD and Rhinosinusitis and Its Impact in Korea Kwang-Ha Yoo, Sang-Heon Cho, AG Ghoshal, Abdul Razak Bin Abdul Muttalif, Horng- Chyuan Lin, Sanguansak Thanaviratananich, Shalini Bagga, Rab Faruqi, Santwona Baidya, Colman Taylor, De Yun Wang, Hae-Ryun Ahn, Soon-Kwan Hong, Jong-Woong Kim, Gui-Hyun Nam, Mee-Ja Kim, Jae-Kyoung Park A631 Cysteine Protease Allergen Def f 1 Induces Th2 Cytokines in Mouse Bone Marrow Derived Basophils Via ERK and JNK Dependent Pathways Myung-Hee Yi, Kyoung Yong Jeong, Ju-Yeong Kim, Tai-Soon Yong A632 Novel Multiple Allergy Testing Kit Using Parallel Lines Array (PLA) Technology Bum Joon Kim, Hs Joo, Kj Lim, Jae-Hyun Lee, Jung-Won Park, Kh Yoon, DS Choi A633 Quantitative Rapid Kit for Human Immunoglobulin Hanseung Joo, Bum Joon Kim, Kj Lim, MJ KIM, DS Choi, Kh Yoon A634 Total IgE Measurement By Protia Allergy-Q: Comparison Study with Immunocap Bum Joon Kim, Hanseung Joo, Woo Sang Jung, Kj Lim, DS Choi A635 Prevalence and Risk Factors of Asthma Among Korean Farmers Ji-Hoon Lee, Soon-Chan Kwon, Soo-Jin Lee, Soo Yong Roh, Hogil Kim, Kyeong Joon Lee A636 Dietary Intake and Perceived Immune Status in Young Dutch Women Aurora Van De Loo, Amanda Fernstrand, Johan Garssen, Joris Verster A637 The Effects of Antihistamine Drugs on on-Road Driving Performance Aurora Van De Loo, Johan Garssen, Joris Verster A638 Grass Is Guilty: A Case of Anaphylactic Shock and Asthmatic Status in the Same Time in an Individual Jasmina Golez A639 Cyclic Gamp-AMP(cGAMP) Induces Allergic Inflammation Koji Ozasa, Etsushi Kuroda, Ken Ishii, Ken Ishii A640 Role of Omalizumab in the Setting of Recalcitrate Dermatitis with Extremely Elevated IgE Levels Muhammad Imran, Selina Gierer, John Martinez A641 Follow-up Study on the Natural History of Prawn Allergy Lydia Wong, Bee Wah Lee, Gaik Chin Yap, Genevieve Llanora, Bernard Thong, Lynette Shek A642 Protein-Losing Dermopathy Impairing Growth in Children with Severe Atopic Dermatitis Mohammad S. Ehlayel, Ashraf Soliman A643 Airways Assessment of Aged Nursing Homes Residents Pedro Martins, João Marques, Joana Gomes-Belo, Teresa Palmeiro, Iolanda Caires, Joana Belo, Maria Amália Botelho, Paula Leiria-Pinto, Nuno Neuparth A644 Use of Skin Prick Test, Specific IgE to Shrimp and Rpen a1 to Determine Clinical Reaction to Shrimp in Area with High Prevalence of House Dust Mite Sensitization Narissara Suratannon, Jaichat Mekaroonkamol, Jarungchit Ngamphaiboon, Piyawadee Lertchanaruengrith, Pantipa Chatchatee A645 Identification of Specific IgE-Binding Proteins in Tree of Heaven (Ailanthus altissima) Pollen Gholamali Kardar, Ahmad Majd, Youcef Shahali, Farrokh Ghahremaninejad, Zahra Pourpak, Fateme Mousavi A646 Allergy Immunotherapy Well Tolerated in Children Mahnaz Sadeghi-Shabestari A647 Steinert (DM1) Patients Have IgG1 Deficiency and Should be Screened for Immune Deficiency K. Van Bilsen, O. Manusama, W.a. Dik, M. Van Der Burg, V. H. J. Van Der Velden, V.a.S. H. Dalm, P. M. Van Hagen A648 The Change of Serous Sige and Three Evaluation before and after Sublingual Immunotherapy with Dermatophagoides Farinae for Persistent Allergic Rhinitis Yongping Liu A649 Garlic Extracts Reduce Histamine-Induced Proliferation and Migration of Human Asthmatic Bronchial Smooth Muscle Cells Yi Yeong Jeong A650 A Case of Occupational Contact Dermatitis Caused By N-Acetylcysteine Ji Hye Kim, Moon Gyeong Yoon, Young Min Ye, Yoo Seob Shin, Ga Young Ban, Hae-Sim Park, Hye Min Jung A651 The Association Between Pollen Change and Asthma Attacks Soo Yong Roh, Jaechul Song, Ji-Hoon Lee, Hogil Kim, Jae Young Kim, Kyeong Joon Lee A652 Incidence of Emergency Department Visits and Hospitalizations for Asthma Exacerbations during the Lunar Month in Singapore Lydia Wong, Mohana Rajakulendran, Haripriya Santhanam, Lynette Shek, Tow Keang Lim A653 The Prevalence of Positive Reaction for Skin Prick Test in Korean Farmers and Its Occupational Risk Factors Hogil Kim, Soo-Jin Lee, Ji-Hoon Lee, Soo Yong Roh, Soon-Chan Kwon A654 Drug Allergy in Children: A Three-Years Experience at Dr. Kariadi Hospital Semarang Indonesia Wistiani, Galuh H, Ani Wistiani A655 The Identification of Morphology, Structure and Study of Seasonal Variation of Airborne Fraxinus Excelsior Pollen Grains in the Tehran Gholam Ali Kardar, Maryam Sharifshoushtari, Ahmad Majd, Taher Nejadsattari, Zahra Pourpak, Mostafa Moin A656 Sublingual Immunotherapy in Elderly Rhinitis Patients Sensitized to House Dust Mites Ji Hye Kim, Daehong Seo, Young Min Ye, Hae-Sim Park, Jung-Won Park, Jae-Hyun Lee, Yoo Seob Shin A657 Healthy Ageing Research Center (HARC) As a Platform for Multidisciplinary Approaches to Respiratory Research in the Elderly Marek L. Kowalski, Aleksandra Wardzynska, Marcin Kurowski, Malgorzata / Ewa Pawelczyk, Adam Wysokinski, Iwona Kloszewska, Janina Grzegorczyk, Wojciech Piotrowski, Joanna Makowska A658 Estimation of Cases of Work-Related Asthma Using Capture-Recapture Methods Soon-Chan Kwon, Jaechul Song, Yong-Kyu Kim A659 Primary School Students’ Parents Reported ISAAC Questionnaire in a Low Income Area of Ankara Ilknur Bostanci, Zeynep Sengul Emeksiz, Aysegul Ertugrul, Serap Ozmen, Soner Sahin A660 Usefulness of PC20 Adenosine Monophosphate in Diagnosis and Treatment in Bronchial Asthma Sang-Ha Kim, Myoung Kyu Lee, Won Yeon Lee, Suk Joong Yong, Seok Jeong Lee, Ye-Ryung Jung A661 S100 Calcium Binding Protein A9 in Sputum of Patients with Steroid Naive Asthma: Relation with Airway Obstruction and Nneutrophilc Inflammation Myung Shin Kim, Jong-Sook Park, An-Soo Jang, Choon-Sik Park A662 Risk Factor Asthma in Pediatric Pneumonia Patients Diah Asri Wulandari, Cissy Kartasasmita A663 Prevalence and Risk Factors of Childhood Asthma and Allergic Disease at Exposed Area By Emission of Cement Padang Factory Finny Fitry Yani, Rizanda Machmud, Dhina Lydia Lestari A664 Association Between Serum Level of 25-Hydroxyvitamin D with Atopic Dermatitis Occurrence and Severity in Children Rusdi Rusdi, Yurmalina Yurmalina, Eryati Darwin A665 Thiol-Disulfide Balance in Children with Atopic Dermatitis Ilknur Bostanci, Gulin Karacan, Nazli Ercan, Asuman Colak, Murat Alisik, Gulay Basarir, Ozcan Erel A666 Recurrent Mouth Ulsers Caused By Braces after Developing a Nickel Allergy in Children Ilknur Bostanci, Yasemin Keskin A667 Anaphylactic Reaction to Famotidine with Pheniramine Hypersensitivity Ilkay Koca Kalkan A668 Novel Transcriptomic and Immunoproteotomic Approaches in Identifying Cross-Reactive Allergens Between Crustacean and Molluscs Andreas/Ludwig Lopata, Kyall Zenger, Roni Nugraha, Sandip Kamath A669 Pollen Season and Climate Change in the Continental United States (CONUS) Leonard Bielory, Panos Georgopoulos, Yong Zhang, Wheat Mi, Ting Cai A670 Differences of Change in Der p IgG4 and CD4+CD25+FoxP3+ Treg Cells Between Sublingual and Subcutaneous Immunotherapy with House Dust Mite in Chinese Patients with Allergic Rhinitis MO Xian, Jing Li, Mulin Feng",2016 Apr 19,"['Lee, Heung-Man', 'Park, Il-Ho', 'Shin, Jae-Min', 'Yoon, Hyun-Sun', 'Park, Gyeong Yul', 'Zeher, Margit', 'Matsui, Katsuhiko', 'Tamai, Saki', 'Ikeda, Reiko', 'Suri, Drsushil', 'Suri, Dranu', 'Arani, Marzieh Heidarzadeh', 'Lubis, Azwin', 'Endaryanto, Anang', 'Koga, Shinichiro', 'Suk, Lee Ju', 'Tsuzuki, Yasunobu', 'Kim, Seo Hyeong', 'Shin, Jung U.', 'Noh, Ji Yeon', 'Jin, Shan', 'Jin, Shan', 'Lee, Hemin', 'Lee, Jungsoo', 'Park, Chang Ook', 'Lee, Kwang Hoon', 'Lee, Kwang Hoon', 'Tepetam, Fatma Merve', 'Park, Chun Wook', 'Son, Jee Hee', 'Cho, Soo Ick', 'Cho, Yong Se', 'Byun, Yun Sun', 'Yang, Yoon Seok', 'Chung, Bo Young', 'Kim, Hye One', 'Cho, Hee Jin', 'Katada, Yoshinori', 'Tanaka, Toshio', 'Nakabayashi, Akihiko', 'Nishida, Koji', 'Aoyagi, Kenichi', 'Tsukamoto, Yuki', 'Konma, Kazushi', 'Matsuura, Motoo', 'Park, Jung-Won', 'Harada, Yoshinori', 'Jeong, Kyoung Yong', 'Yura, Akiko', 'Yoshimura, Maiko', 'Kyung, Tae-Suk', 'Kim, Young Hyo', 'Park, Chang-Shin', 'Jang, Tae Young', 'Heo, Min-Jeong', 'Jung, Ah-Yeoun', 'Yang, Seung-Chan', 'Kim, Hye One', 'Cho, Yong Se', 'Byun, Yun Sun', 'Yang, Yoon Seok', 'Chung, Bo Young', 'Son, Jee Hee', 'Park, Chun Wook', 'Cho, Hee Jin', 'Pfaar, Oliver', 'Sager, Angelika', 'Agarwal, Amit', 'Singh, Meenu', 'Chatterjee, Bishnupda', 'Chauhan, Anil', 'Striz, Ilja', 'Cecrdlova, Eva', 'Petrickova, Katerina', 'Kolesar, Libor', 'Sekerkova, Alena', 'Svachova, Veronika', 'Petricek, Miroslav', 'Kwon, Hyuck Hoon', 'Kim, Kyu Han', 'Kumar, Suman', 'Manzon, Lou Ver Leigh Arciaga', 'Andaya, Pilar Agnes Gonzalez', 'Lew, Bark-Lynn', 'Oh, Youngjun', 'Suh, Dongwoo', 'Sim, Woo-Young', 'Jeong, Kyoung Yong', 'Yi, Myung-Hee', 'Son, Mina', 'Lyu, Dongpyo', 'Lee, Jae-Hyun', 'Yong, Tai-Soon', 'Hong, Chein-Soo', 'Park, Jung-Won', 'Jeong, Kyoung Yong', 'Yi, Myung-Hee', 'Son, Mina', 'Lyu, Dongpyo', 'Lee, Jae-Hyun', 'Yong, Tai-Soon', 'Hong, Chein-Soo', 'Park, Jung-Won', 'Siavashi, Mohammadreza', 'Yun, Hey Suk', 'Kang, Ha-Na', 'Oh, Jae-Won', 'Choi, Young Jin', 'Oh, Jae-Won', 'Choi, Young Jin', 'Kang, Ha-Na', 'Sentsova, Tatiana', 'Vorozhko, Ilya', 'Chernyak, Olga', 'Revyakina, Vera', 'Timopheeva, Anna', 'Donnikov, Andrey', 'Sentsova, Tatiana', 'Vorozhko, Ilya', 'Chernyak, Olga', 'Revyakina, Vera', 'Timopheeva, Anna', 'Lee, Ji Hyun', 'Park, Young Min', 'Choi, Sang Soo', 'Han, Kyung Do', 'Jung, Han Mi', 'Youn, Young Hoon', 'Lee, Jun Young', 'Park, Yong Gyu', 'Lee, Seung-Hwan', 'Li, Jing', 'Feng, Mulin', 'Roponen, Marjut', 'Schaub, Bianca', 'Wong, Gary W. K.', 'Yang, Zhaowei', 'Choi, Young Jin', 'Kang, Ha-Na', 'Oh, Jae-Won', 'Sun, Baoqing', 'Zheng, Peiyan', 'Park, Yoon-Sung', 'Son, Sang Wook', 'Kose, Sukran', 'Kiraz, Kemal', 'Yalcin, Arzu Didem', 'Yune, Sehyo', 'Paeng, Jae-Won', 'Oh, Mi-Jung', 'Lee, Byung-Jae', 'Choi, Dong-Chull', 'Lim, Young Hee', 'Ha, Kyoung Won', 'Lee, Jin-Young', 'Yamamoto-Hanada, Kiwako', 'Narita, Masami', 'Futamura, Masaki', 'Ohya, Yukihiro', 'Kim, Jihyun', 'Choi, Jinwha', 'Kim, Kwanghoon', 'Choi, Jaehee', 'Ahn, Kangmo', 'Chang, Sun-Ho/Brian', 'Li, Lisha', 'Adachi, Yu-Ichi', 'Kanatani, Kumiko Tsuji', 'Narabayashi, Shigeyuki', 'Okafuji, Ikuo', 'Tanaka, Yuya', 'Tsuruta, Satoru', 'Takamatsu, Nobue', 'Kim, Soo Whan', 'Kim, Do Hyun', 'Yoon, Jong-Seo', 'Kim, Jin Tack', 'Kim, Hwan Soo', 'Chun, Yoon Hong', 'Kim, Hyun Hee', 'Won, Sul Mui', 'Hon, Kam Lun E.', 'Chow, Chung Mo', 'Leung, Ting Fan', 'Kim, Do Hyun', 'Kim, Soo Whan', 'Esguerra, Gemmalyn', 'Resurreccion, Emily', 'Kionisala, Kristine Elisa', 'Dela Cruz, Jenni Rose', 'Imran, Muhammad', 'Choe, Yun Seon', 'Kim, Kyu Han', 'Choi, Mira', 'Kim, Byung Soo', 'Lee, Hyun-Joo', 'Kim, Jeong-Min', 'Kim, Jeong-Min', 'Kim, Gun-Wook', 'Mun, Je-Ho', 'Mun, Je-Ho', 'Kim, Hoon-Soo', 'Song, Margaret', 'Ko, Hyun-Chang', 'Ko, Hyun-Chang', 'Kim, Moon-Bum', 'Yoon, Sun-Young', 'Kandhare, Amit', 'Yahiro, Noriko', 'Agarwal, Amit', 'Singh, Meenu', 'Kaur, Jasleen', 'Pawankar, Ruby', 'Pant, Pankaj', 'Singh, Sukhmanjeet', 'Kim, Hwan Soo', 'Yoon, Jong-Seo', 'Won, Sul Mui', 'Chun, Yoon Hong', 'Kim, Jin Tack', 'Kim, Hyun Hee', 'Kim, Hwan Soo', 'Won, Sul Mui', 'Chun, Yoon Hong', 'Yoon, Jong-Seo', 'Kim, Hyun Hee', 'Kim, Jin Tack', 'Kampitak, Thatchai', 'Kim, So Min', 'Lee, Hyun Joo', 'Kim, Hei Sung', 'Lee, Jeong Deuk', 'Cho, Sang Hyun', 'Godse, Kiran', 'Soekarno, Juwita', 'Ratnasari, Sarie', 'Datau, E. Alwi', 'Surachmanto, Eko', 'Matheos, JC', 'Leung, Ting Fan', 'Kwok, Jamie Sui-Lam', 'Tung, Christine Kit-Ching', 'Tang, Man Fung', 'Tsui, Stephen Kwok-Wing', 'Wong, Gary WK', 'Hon, Kam Lun Ellis', 'Tam, Wing Hung', 'Sy, Hing Yee', 'Lee, Sohee', 'Shin, Hyun-Woo', 'Lee, Mingyu', 'Kim, Dae Woo', 'Khalmuratova, Roza', 'Kim, Mi Yeoung', 'Jeong, Jaewon', 'Park, Chansun', 'Wai, Christine Yee Yan', 'Leung, Patrick S. C.', 'Leung, Nicki Y. H.', 'Chu, Ka Hou', 'Lee, Hee Seon', 'Lee, Kyung Eun', 'Hong, Jung Yeon', 'Kim, Mi Na', 'Kim, Min Jung', 'Kim, Yoon Hee', 'Sol, In Suk', 'Yoon, Seo Hee', 'Kim, Kyung Won', 'Sohn, Myung Hyun', 'Kim, Kyu-Earn', 'Kim, Ji Hye', 'Park, Hae-Sim', 'Shin, Yoo Seob', 'Ye, Young Min', 'Seo, Daehong', 'Yoon, Moon Gyeong', 'Lee, Young Mok', 'Seo, Daehong', 'Kim, Ji Hye', 'Lee, Young-Mok', 'Ye, Young Min', 'Park, Hae-Sim', 'Ban, Ga Young', 'Cho, Kumsun', 'Kim, Seung-Hyun', 'Kwon, Yong Eun', 'Yoon, Moon Gyeong', 'Kim, Ji Hye', 'Shin, Yoo Seob', 'Ye, Young Min', 'Nahm, Dong-Ho', 'Park, Hae-Sim', 'Andaya, Pilar Agnes Gonzalez', 'Andaya, Pilar Agnes Gonzalez', 'Ban, Ga Young', 'Jung, Chang Gyu', 'Lee, Seung-Ihm', 'Le Pham, Duy', 'Suh, Dong-Hyeon', 'Yang, Eun-Mi', 'Ye, Young Min', 'Shin, Yoo Seob', 'Park, Hae-Sim', 'Wang, Wan Jun', 'Xian, MO', 'Xie, Yan Qing', 'Zheng, Jing Ping', 'Li, Jing', 'Savilahti, Emma Merike', 'Mäkitie, Outi', 'Kukkonen, Anna Kaarina', 'Andersson, Sture', 'Viljakainen, Heli', 'Savilahti, Erkki', 'Kuitunen, Mikael', 'Godse, Kiran', 'Le Pham, Duy', 'Ban, Ga Young', 'Kim, Seung-Hyun', 'Yang, Eun-Mi', 'Park, Hae-Sim', 'Lee, Ji-Ho', 'Chwae, Yong-Joon', 'Chin, Li-Ming', 'Shieh, Chi-Chang', 'Kim, Ji Hye', 'Yoo, Hye-Soo', 'Yoon, Moon Gyeong', 'Ban, Ga Young', 'Ban, Ga Young', 'Shin, Yoo Seob', 'Ye, Young Min', 'Park, Hae-Sim', 'Sung, Myong Soon', 'Choi, Jin Uck', 'Kim, Sung Won', 'Hwang, Yong Jin', 'Park, Arum', 'Lee, Eun', 'Yang, Song-I', 'Cho, Hyun-Ju', 'Yu, Jinho', 'Lee, Dong Hun', 'Kim, Eun Ju', 'Kim, Yeon Kyung', 'Doh, Eun Jin', 'Eun, Hee Chul', 'Chung, Jin Ho', 'Lee, Young Mee', 'Jin, Seon Pil', 'Li, Xingnan', 'Kaminski, Naftali', 'Wenzel, Sally', 'Bleecker, Eugene', 'Meyers, Deborah', 'Huasong, Zeng', 'Mo, Ji-Hun', 'Samivel, Ramachandran', 'Kim, Eun-Hee', 'Kim, Ji-Hye', 'Bae, Jun-Sang', 'Chung, Young-Jun', 'Kim, Dae Woo', 'Lee, Eun', 'Lee, Si Hyeon', 'Kim, Young-Ho', 'Cho, Hyun-Ju', 'Yu, Ho-Sung', 'Kang, Mi-Jin', 'Yang, Song-I', 'Jung, Young-Ho', 'Kim, Hyung Young', 'Seo, Ju-Hee', 'Kim, Byoung-Ju', 'Kim, Hyo-Bin', 'Lee, So-Yeon', 'Kwon, Ho-Jang', 'Hong, Soo-Jong', 'Palikhe, Sailesh', 'Park, Hae-Sim', 'Kim, Seung-Hyun', 'Kim, Ji Hye', 'Yang, Eun-Mi', 'Sibunruang, Suda', 'Klaewsongkram, Jettanong', 'Sentsova, Tatiana', 'Vorozhko, Ilya', 'Timopheeva, Anna', 'Chernyak, Olga', 'Revyakina, Vera', 'Sokolnikov, Andrey', 'Nisihino, Makoto', 'Okada, Yu', 'Yanagida, Noriyuki', 'Ebisawa, Motohiro', 'Sato, Sakura', 'Ogura, Kiyotake', 'Asaumi, Tomoyuki', 'Nagakura, Kenichi', 'Manabe, Tetsuharu', 'Unno, Hirotoshi', 'Rodrigues, Pedro M.', 'Schrama, Denise', 'Mohamed, Gadija', 'Hüsselmann, Lizex', 'Hüsselmann, Lizex', 'Ndimba, Bongani', 'Shim, Jae-Uoong', 'Koh, Young Il', 'Rhee, Joon Haeng', 'Jeong, Ji-Ung', 'Van Nguyen, Dinh', 'Chu, Hieu Chi', 'Tran, Mui Thi', 'Vidal, Christopher', 'Fernando, Suran', 'Van Nunen, Sheryl', 'Van Than, Sy', 'Feng, Mulin', 'Li, Jing', 'Kim, Dong-Kyu', 'Hong, Seung-No', 'Eun, Kyoung Mi', 'Jin, Hong Ryul', 'Kim, Dae Woo', 'Bao, Jun', 'Bao, Yi-Xiao', 'Podder, Sanjoy', 'Kumar, Goutam', 'Dutta, Shampa', 'Ghosh, Amlan', 'Saha, Goutam Kumar', 'Podder, Sanjoy', 'Gupta, Salil Kumar', 'Trinh, Tu/Hoang Kim', 'Shin, Yoo Seob', 'Park, Hae-Sim', 'Liu, Jing-Nan', 'Le Pham, Duy', 'Ko, Hyun-Chang', 'Kim, Byung Soo', 'Kim, Moon-Bum', 'Özbudak, Ömer', 'Üzer, Fatih', 'Al-Ahmad, Mona', 'Alowayesh, Maryam', 'Carroll, Norman', 'Singh, Anand Bahadur', 'Pérez-Llano, Yordanis', 'Lorenzo, María Del Carmen Luzardo', 'González, Wendy Ramírez', 'Cruz, Carlos Calcines', 'Quintana, Rady Laborde', 'Morejón, Alain', 'Bourg, Virgilio', 'Stoker, Marilé Hechavarría', 'Bae, Jun-Sang', 'Samivel, Ramachandran', 'Kim, Eun-Hee', 'Kim, Ji-Hye', 'Mo, Ji-Hun', 'Hanaoka, Keiko', 'Hide, Michihiro', 'Tanaka, Akio', 'Hiragun, Makiko', 'Kawai, Mikio', 'Kim, Kwanghoon', 'Kim, Hye-Young', 'Kim, Jihyun', 'Ahn, Kangmo', 'Han, Youngshin', 'Kim, Gun-Wook', 'Ko, Hyun-Chang', 'Kim, Byung Soo', 'Kim, Moon-Bum', 'Song, Margaret', 'Matsubara, Takeshi', 'Iwamoto, Hiroshi', 'Nakazato, Yuki', 'Namba, Kazuyoshi', 'Takeda, Yasuhiro', 'Lee, Jae Hoon', 'Bae, Woo Yong', 'De Schryver, Els', 'Calus, Lien', 'Gevaert, Philippe', 'Van Zele, Thibaut', 'Bachert, Claus', 'Mori, Akio', 'Kouyama, Satoshi', 'Yamaguchi, Miyako', 'Iijima, Yo', 'Abe-Ohtomo, Akemi', 'Hayashi, Hiroaki', 'Watai, Kentaroh', 'Mitsui, Chihiro', 'Oshikata, Chiyako', 'Sekiya, Kiyoshi', 'Tsuburai, Takahiro', 'Ohtomo, Mamoru', 'Fukutomi, Yuma', 'Taniguchi, Masami', 'Kang, Ju Wan', 'Kim, Jeong Hong', 'Kim, Jeong Hong', 'Lee, Keun-Hwa', 'Lee, Hye-Sook', 'Hong, Seong-Chul', 'Lee, Jaechun', 'Seo, Ji Won', 'Lee, Jae Hoon', 'Bae, Woo Yong', 'Kuznecovs, Ivans Sergejs', 'Kuznecova, Galina', 'Bergmann, Karl-Christian', 'Zuberbier, Torsten', 'Salame, Joseph', 'Sehlinger, Torsten', 'Bölke, Georg', 'Kim, Yoo Suk', 'Chang, Jung Hyun', 'Kim, Jeong Hong', 'Kang, Ju Wan', 'Hong, Seung-No', 'Han, Doo Hee', 'Rhee, Chae-Seo', 'Ko, Young-Joo', 'Kim, Young Hyo', 'Kim, Dae-Young', 'Jang, Tae Young', 'Yokooji, Tomoharu', 'Hirano, Taiki', 'Matsuo, Hiroaki', 'Kuznecova, Galina', 'Kuznecovs, Ivans Sergejs', 'Wani, Roohi Rasool', 'Syed, Shafia Alam', 'Hassan, Ghulam', 'Gul, Ayaz', 'Nissar, Saniya', 'Shah, Zaffar Amin', 'Pereira, Marilyn Urrutia', 'Fernandez, Carmen', 'Sole, Dirceu', 'Neto, Herberto Jose Chong', 'Acosta, Veronica', 'Cepeda, Alfonso Mario', 'Castello, Mirta Alvarez', 'Almendarez, Claudia', 'Saenz, Jose Santos Lozano', 'Sisul, Juan C.', 'Filho, Nelson Rosario', 'Castillo, Antonio', 'Rostan, Marylin Valentin', 'Avila, Jennifer', 'Badellino, Hector', 'Manotas, Maria Carolina', 'Almarales, Raúl Lázaro Castro', 'León, Mayda González', 'Kim, Woo Kyung', 'Yoon, Hae-Sun', 'Kobayashi, Takehito', 'Noguchi, Tooru', 'Soma, Tomoyuki', 'Nakagome, Kazuyuki', 'Nakamoto, Hidetomo', 'Kita, Hirohito', 'Nagata, Makoto', 'Pereira, Marilyn Urrutia', 'Sole, Dirceu', 'Neto, Herberto Jose Chong', 'Cepeda, Alfonso Mario', 'Almarales, Raúl Lázaro Castro', 'Sisul, Juan C.', 'Rostan, Marylin Valentin', 'Badellino, Hector', 'Avalos, Miguel Alejandro Medina', 'Castillo, Antonio', 'Almendarez, Claudia', 'Filho, Nelson Rosario', 'Silot, Caridad Sanchez', 'Avila, Jennifer', 'Rodriguez, Felicia Berroa', 'Saenz, Jose Santos Lozano', 'Castello, Mirta Alvarez', 'Fernandez, Carmen', 'Soh, Wai Tuck', 'Jacquet, Alain', 'Ruxrungtham, Kiat', 'Nony, Emmanuel', 'Le Mignon, Maxime', 'Lee-Wong, Mary', 'McClelland, Suzanne', 'McClelland, Suzanne', 'Silverberg, Nanette B.', 'Song, Christian E.', 'Yang, Zhaowei', 'Zhang, Jiukai', 'Zheng, Wentao', 'Zhong, Nanshan', 'Li, Jing', 'Bae, Jung Ho', 'Cho, Young Joo', 'Kim, Joo Yeon', 'Vourdas, Dimitrios', 'Grigoreas, Christos', 'Petalas, Konstantinos', 'Zhang, Yuan', 'Shin, Seung-Heon', 'Ye, Mi-Kyung', 'Kim, Jeong-Kyu', 'Feng, Yong', 'Shang, Yunxiao', 'Seo, Sungchul', 'Choung, Ji Tae', 'Kim, Dohyeong', 'Yoo, Young', 'Lim, Hyunwook', 'Zhu, Wenjing', 'Liu, Chuanhe', 'Sha, Li', 'Chang, Li', 'Zhao, Min', 'Zhao, Linqing', 'Qian, Yuan', 'Chen, Yuzhi', 'Kim, Min-Hye', 'Cho, Young Joo', 'Rho, Mina', 'Kim, Jung-Won', 'Kang, Yeon-Mi', 'Yum, Kyung-Eun', 'Choi, Hyeon-Il', 'Choi, Jun-Pyo', 'Park, Han-Ki', 'Min, Taek-Ki', 'Pyun, Bok-Yang', 'Kim, Yoon-Keun', 'Wang, Xueyan', 'Kim, Woo Kyung', 'Nam, Yu Ran', 'Nam, Joo Hyun', 'Kim, Jung-Won', 'Kim, Min-Hye', 'Rho, Mina', 'Kang, Yeon-Mi', 'Yum, Kyung-Eun', 'Choi, Hyeon-Il', 'Choi, Jun-Pyo', 'Park, Han-Ki', 'Min, Taek-Ki', 'Cho, Young Joo', 'Pyun, Bok-Yang', 'Kim, Yoon-Keun', 'Narita, Hiroshi', 'Hirose, Junko', 'Kizu, Kumiko', 'Matsunaga, Ayu', 'Li, Jingyun', 'Zhang, Yuan', 'Zhang, Luo', 'Choi, Yean Jung', 'Shin, Hye Lim', 'Yang, Song-I', 'Lee, So-Yeon', 'Kwon, Sung-Ok', 'Jung, Young-Ho', 'Kwon, Ji-Won', 'Kim, Hyung Young', 'Seo, Ju-Hee', 'Kim, Byoung-Ju', 'Kim, Hyo-Bin', 'Oh, Se-Young', 'Kwon, Ho-Jang', 'Lee, Eun', 'Kang, Mi-Jin', 'Hong, Soo-Jong', 'Lee, Yun-Jeong', 'Kim, Joonil', 'Choi, Joon Young', 'Kang, Ji Young', 'Kim, Seok Chan', 'Kim, Sei Won', 'Kim, Seung Joon', 'Kim, Young Kyoon', 'Rhee, Chin Kook', 'Lee, Hea Yon', 'Lee, Hwa Young', 'Lee, Sook Young', 'Koh, Tae Kyung', 'Kim, Sung Wan', 'Lee, Kun Hee', 'Kwon, Chul', 'Jo, Joong-Saeng', 'Dong, Sung-Hwa', 'Byun, Young Seok', 'Song, Charles', 'Kang, Ji Young', 'Lee, Hwa Young', 'Kim, In Kyoung', 'Kim, Sei Won', 'Rhee, Chin Kook', 'Kim, Seung Joon', 'Kim, Seok Chan', 'Lee, Sook Young', 'Kim, Young Kyoon', 'Kwon, Soon Seog', 'Choi, Joon Young', 'Park, Pona', 'Jin, Hong Ryul', 'Kim, Dong-Kyu', 'Kim, Dae Woo', 'Hogenkamp, Astrid', 'Knippels, Leon', 'Van Esch, Betty C.a.m.', 'Van Bilsen, Jolanda', 'Jeurink, Prescilla V.', 'Gros, Marjan', 'Garssen, Johan', 'Smit, Joost J.', 'Pieters, Raymond H. H.', 'Kim, Boo-Young', 'Kim, Soo Whan', 'Lleonart, Ramon', 'Lay, Christophe', 'Benamor, Kaouther', 'Chen, Chua Mei', 'Knol, Jan', 'Chew, Charmaine', 'Chongsrisawat, Voranush', 'Goh, Anne', 'Chiang, Wen Chin', 'Rao, Rajeshwar', 'Chaithongwongwatthana, Surasith', 'Khemapech, Nipon', 'Yhi, Ji Young', 'Kim, Sang-Heon', 'Park, Dong Won', 'Moon, Ji-Yong', 'Kim, Tae Hyung', 'Sohn, Jang Won', 'Shin, Dong Ho', 'Yoon, Ho Joo', 'Cho, Seok Hyun', 'Kim, Sang-Heon', 'Moon, Ji-Yong', 'Lee, Jae-Hyun', 'Ban, Ga Young', 'Kim, Sujeong', 'Kim, Mi-Ae', 'Kim, Joo-Hee', 'Kim, Min-Hye', 'Park, Chan-Sun', 'Kwon, Hyouk-Soo', 'Kwon, Jae-Woo', 'Jung, Jae Woo', 'Kang, Hye-Ryun', 'Park, Jong-Sook', 'Kim, Tae-Bum', 'Park, Heung Woo', 'Cho, You Sook', 'Yoo, Kwang-Ha', 'Oh, Yeon-Mok', 'Lee, Sang-Rok', 'Julge, Kaja', 'Vasar, Maire', 'Vasar, Maire', 'Voor, Tiia', 'Rebane, Tiina', 'Kim, Yu Jin', 'Lee, Sang Min', 'Kang, Shin Myung', 'Kim, Sojeong', 'Kyung, Sun Young', 'Jeong, Sung Hwan', 'Park, Jeong-Woong', 'Hwang, Hyunjung', 'Seon, Yong Han', 'Park, Sanghui', 'Lee, Sang Pyo', 'Iordache, Marius', 'Jeong, Yeongsang', 'Eun, Sohee', 'Choi, Byung Min', 'Choung, Ji Tae', 'Seo, Wonhee', 'Zhang, Liang', 'Pawankar, Ruby', 'Nonaka, Manabu', 'Hayashi, Miyuki', 'Yamanishi, Shingo', 'Suzaki, Harumi', 'Itoh, Yasuhiko', 'Watanabe, So', 'Kobayashi, Hitome', 'Zotter, Zsuzsanna', 'Farkas, Henriette', 'Varga, Lilian', 'Veszeli, Nora', 'Imreh, Eva', 'Kovacs, Gabor', 'Nallbani, Marsel', 'Zheleznov, Semen', 'Urzhumtseva, Galina', 'Petrova, Natalia', 'Sarsaniia, Zhanna', 'Didkovskii, Nikolai', 'Zuberbier, Torsten', 'Gerdabi, Nader Dashti', 'Khodadadi, Ali', 'Abdoli, Zahra', 'Ghafourian, Mehri', 'Assarehzadegan, Mohammad Ali', 'Ghorban, Khodayar', 'Kim, Hyo-Bin', 'Zhou, Hui', 'Kim, Jeong Hee', 'Habre, Rima', 'Bastain, Theresa', 'Gilliland, Frank', 'Bae, Jong-Wook', 'Han, Kyu-Hyung', 'Jee, Young-Koo', 'Choi, Misoo', 'Hong, Seung-Phil', 'Kim, Seung-Hyun', 'Kim, Hee-Kyoo', 'Choi, Gil-Soon', 'Heo, Jeonghoon', 'Kim, Young-Ho', 'Park, Eun-Kee', 'Inoue, Takashi', 'Ogura, Kiyotake', 'Yanagida, Noriyuki', 'Unno, Hirotoshi', 'Nagakura, Kenichi', 'Manabe, Tetsuharu', 'Asaumi, Tomoyuki', 'Sato, Sakura', 'Okada, Yu', 'Ebisawa, Motohiro', 'Kim, Min-Gu', 'Cho, You Sook', 'Kim, Tae-Bum', 'Moon, Hee-Bom', 'Kim, Jung-Hyun', 'Kim, Hyo-Jung', 'Park, So-Young', 'Seo, Bomi', 'Kwon, Hyouk-Soo', 'Lee, Jaemoon', 'Lee, Taehoon', 'Yoo, Hye-Soo', 'Kim, Jieun', 'Kim, Inok', 'Kim, Haejin', 'Chang, Younhee', 'Park, Hae-Sim', 'Lee, Sooyoung', 'Lee, Sooyoung', 'Kuzume, Kazuyo', 'Koizumi, Munemitsu', 'Nishimura, Koji', 'Okamoto, Michiko', 'Kim, Seung-Hyun', 'Ye, Young Min', 'Hur, Gyu Young', 'Park, Hae-Sim', 'Kim, Sang-Heon', 'Jee, Young-Koo', 'Kim, Seung-Hyun', 'Choi, Hyunna', 'Ye, Young Min', 'Park, Hae-Sim', 'Van Khanh, Bui', 'Chu, Hieu Chi', 'Nguyet, Nguyen Nhu', 'Phuong, Nguyen Hoang', 'Roh, Joo Young', 'Kim, Hyun Jeong', 'Kim, Jung Eun', 'Lew, Bark-Lynn', 'Lee, Kyung Ho', 'Hong, Seung-Phil', 'Jang, Yong Hyun', 'Park, Kui Young', 'Seo, Seong Jun', 'Bae, Jung Min', 'Choi, Eung Ho', 'Suhr, Ki Beom', 'Lee, Seung Chul', 'Ko, Hyun-Chang', 'Park, Young Lip', 'Son, Sang Wook', 'Seo, Young Jun', 'Lee, Yang Won', 'Cho, Sang Hyun', 'Park, Chun Wook', 'Lee, Kun Hee', 'Kim, Sung Wan', 'Chu, Chia-Yu', 'Aw, Derrick', 'Ye, Young-Min', 'Bader, Giovanni', 'Dolfi, Fabrizio', 'Oliveira, Nathalie', 'Choi, Jae Chol', 'Jung, Jae Woo', 'Kang, Hye-Ryun', 'Kim, Kijeong', 'Choi, Byoung Whui', 'Shin, Jong Wook', 'Jung, Jae Woo', 'Choi, Jae Chol', 'Park, In Won', 'Choi, Byoung Whui', 'Kim, Jae Yeol', 'Lee, Jin-Young', 'Ha, Kyoung Won', 'Jeung, Yun-Jin', 'Yune, Sehyo', 'Lee, Byung-Jae', 'Choi, Dong-Chull', 'Oh, Mi-Jung', 'Lim, Young Hee', 'Lee, Eui Jun', 'Suh, Dongin', 'Suh, Dongin', 'Woo, Sung-Il', 'Woo, Sung-Il', 'Cho, Hwa Jin', 'Cho, Hwa Jin', 'Chung, Eun Hee', 'Chung, Eun Hee', 'Chung, Soo Youn', 'Shah, Ashok', 'Gera, Kamal', 'Ha, Kyoung Won', 'Oh, Mi-Jung', 'Lim, Young Hee', 'Yune, Sehyo', 'Paeng, Jae-Won', 'Jang, Mi-Jin', 'Lee, Byung-Jae', 'Choi, Dong-Chull', 'Lee, Jin-Young', 'Jang, Mi-Jin', 'Paeng, Jae-Won', 'Jeung, Yun-Jin', 'Lim, Young Hee', 'Oh, Mi-Jung', 'Ha, Kyoung Won', 'Lee, Byung-Jae', 'Choi, Dong-Chull', 'Yune, Sehyo', 'Lee, Jin-Young', 'Ito, Takahiro', 'Lee, Jin-Young', 'Yune, Sehyo', 'Lee, Byung-Jae', 'Choi, Dong-Chull', 'Jang, Mi-Jin', 'Paeng, Jae-Won', 'Kim, Young Eun', 'Kim, Young Nam', 'Lee, Yongseok', 'Kim, Jihye', 'Lee, Hwa Young', 'Lee, Sook Young', 'Kwon, Soon Seog', 'Kim, Young Kyoon', 'Rhee, Chin Kook', 'Kim, Sei Won', 'Lee, Hea Yon', 'Choi, Joon Young', 'Kim, In Kyoung', 'Aranzabal, Maria Ascension', 'Joral, Alejandro', 'Lizarza, Susana', 'Echenagusia, Miguel', 'Lasa, Eva Maria', 'Navarro, Jose Antonio', 'Jo, Eun-Jung', 'Jang, Sun-Mi', 'Song, Seung-Eon', 'Na, Hae-Jung', 'Kim, Chang-Hoon', 'Lee, Woo-Seop', 'Park, Hye-Kyung', 'Miyauchi, Sachiko', 'Uchida, Yoshitaka', 'Soma, Tomoyuki', 'Yamazaki, Susumu', 'Noguchi, Toru', 'Kobayashi, Takehito', 'Nakagome, Kazuyuki', 'Nagata, Makoto', 'Oh, Hea Lin', 'Kim, Do Kyun', 'Suh, Dongin', 'Koh, Young Yull', 'Lee, Jin-Young', 'Lee, Byung-Jae', 'Choi, Dong-Chull', 'Paeng, Jae-Won', 'Jang, Mi-Jin', 'Kim, Jihye', 'Kim, Young Nam', 'Yune, Sehyo', 'Kim, Sang-Hoon', 'Sohn, Jang Won', 'Yoon, Ho Joo', 'Shin, Dong Ho', 'Lee, Jae Hyung', 'Lee, Byoung Hoon', 'Kim, Youn-Seup', 'Park, Jae-Seuk', 'Jee, Young-Koo', 'Kim, Sang-Heon', 'Lee, Jin-Young', 'Paeng, Jae-Won', 'Jang, Mi-Jin', 'Choi, Dong-Chull', 'Lee, Byung-Jae', 'Lee, Yongseok', 'Kim, Young Eun', 'Yune, Sehyo', 'Yoon, Jisun', 'Zhang, Li', 'Cai, Xuxu', 'Feng, Yong', 'Yoon, Jong-Seo', 'Jeong, Kyunguk', 'Yoo, Hye-Soo', 'Lee, Sooyoung', 'Lee, Sooyoung', 'Lee, Hae-Jin', 'Lee, Noo Ri', 'Kim, Bo-Kyung', 'Jung, Minyoung', 'Kim, Dong Hye', 'Moniaga, Catharina S.', 'Kabashima, Kenji', 'Choi, Eung Ho', 'Yanagida, Noriyuki', 'Sato, Sakura', 'Sugizaki, Chizuko', 'Ebisawa, Motohiro', 'Kiehm, Jamie', 'Ponda, Punita', 'Farzan, Sherry', 'Weiss, Jared', 'Elera, Claudia', 'Destio, Catherine', 'Sison, Cristina', 'Lee, Annette', 'Ri, Soo Hyun', 'Lim, Chang Hoon', 'Pulido, Iñaki Izquierdo', 'Taubel, Jorg', 'Ferber, Georg', 'Masdeu, Eva Santamaria', 'Khayatzadeh, Alireza', 'Movahedi, Masoud', 'Ebisawa, Motohiro', 'Gharagozlou, Mohammad', 'Atasoy, Ulus', 'Techasintana, Patsharaporn', 'Gubin, Matt', 'Glascock, Jacqueline', 'Ridenhour, Suzanne', 'Magee, Joseph', 'Filho, Nelson Rosario', 'Neto, Herberto Jose Chong', 'Wandalsen, Gustavo Falbo', 'Dela Bianca, Ana Caroline', 'Aranda, Carolina', 'Sole, Dirceu', 'Mallol, Javier', 'Garcia-Marcos, Luis', 'Garcia-Marcos, Luis', 'Toh, Jennifer', 'Lee, Yoomie', 'Huang, Joyce', 'Jerschow, Elina', 'Shliozberg, Jenny', 'Satitsuksanoa, Pattraporn', 'Suratannon, Narissara', 'Wongpiyabovorn, Jongkonnee', 'Chatchatee, Pantipa', 'Ruxrungtham, Kiat', 'Jacquet, Alain', 'Yang, Min Suk', 'Lee, Jin Yong', 'Kim, Ja Yeun', 'Park, Han-Ki', 'Kim, Ju-Young', 'Song, Woo-Jung', 'Kang, Hye-Ryun', 'Park, Heung Woo', 'Chang, Yoon-Seok', 'Cho, Sang-Heon', 'Min, Kyung-up', 'Park, Chang-Han', 'Chang, Suk-Il', 'Song, Sook-Hee', 'Kim, Si-Heon', 'Choi, Gil-Soon', 'Kim, Su-Chin', 'Kim, Ji Hye', 'Ban, Ga Young', 'Shin, Yoo Seob', 'Park, Hae-Sim', 'Ye, Young Min', 'Hwang, Yoon Ha', 'Sim, Da Woon', 'Park, Kyung Hee', 'Park, Kyung Hee', 'Park, Hye Jung', 'Park, Hye Jung', 'Park, Jung-Won', 'Park, Jung-Won', 'Lee, Jae-Hyun', 'Lee, Jae-Hyun', 'Allen, Katrina', 'Beck, Cara', 'Koplin, Jennifer', 'Matheson, Melanie', 'Tang, Mimi', 'Ponsonby, Anne-Louise', 'Gurrin, Lyle', 'Dharmage, Shyamali', 'Wake, Melissa', 'Mcwilliam, Vicki', 'Liu, Xiaoying', 'Wang, Jing', 'Xiang, Li', 'Wang, Qun', 'Lee, Ji-Eun', 'Kim, Dong-Young', 'Rhee, Chae-Seo', 'Rhee, Chae-Seo', 'Vazquez-Nava, Francisco', 'Cho, Sang-Heon', 'Jeong, Jaewon', 'Perng, Diahn-Warng', 'Price, David', 'Neira, Glenn', 'Lin, Jiangtao', 'Semernik, Olga', 'Kim, Ha-Su', 'Jung, Jin-a', 'Jung, Ji-in', 'Miao, Qing', 'Xiang, Li', 'Cho, Sang-Heon', 'Jeong, Jaewon', 'Perng, Diahn-Warng', 'Lin, Jiangtao', 'Price, David', 'Neira, Glenn', 'Lee, Hyun Young', 'Park, Hae-Sim', 'Ye, Young Min', 'Kim, Su Chin', 'Farrokhi, Shokrollah', 'Gheiby, Mohammadkazem', 'Kim, Sang-Heon', 'Park, Heung Woo', 'Kim, Sang-Hoon', 'Jee, Young-Koo', 'Park, Sunjoo', 'Moon, Keun Ai', 'Kwon, Hyouk-Soo', 'Kim, Tae-Bum', 'Cho, You Sook', 'Moon, Hee-Bom', 'Lee, Kyoung Young', 'Hong, Gyong Hwa', 'Ha, Eun Hee', 'Han, Heejae', 'Park, Hye Jung', 'Park, Yoon Hee', 'Kim, Yoon-Jo', 'Lee, Kangtaek', 'Park, Jung-Won', 'Lee, Jae-Hyun', 'Slavyanskaya, Tatiana', 'Derkach, Vladislava', 'Park, Hye Jung', 'Hong, Chein-Soo', 'Lee, Jae-Hyun', 'Kim, Sungryeol', 'Park, Kyung Hee', 'Lee, Choong-Kun', 'Kang, Beodeul', 'Beom, Seung-Hoon', 'Shin, Sang Joon', 'Jung, Minku', 'Park, Jung-Won', 'Kim, Eun-Hee', 'Kim, Ji-Hye', 'Mo, Ji-Hun', 'Chung, Young-Jun', 'Kim, Mi-Ae', 'Park, Hae-Sim', 'Yoon, Moon Gyeong', 'Lee, Young-Soo', 'Kim, Ji Hye', 'Ban, Ga Young', 'Yoo, Hye-Soo', 'Shin, Yoo Seob', 'Ye, Young Min', 'Nahm, Dong-Ho', 'Miao, Qing', 'Xiang, Li', 'Li, Ying-Ji', 'Shimizu, Takako', 'Inagaki, Hirofumi', 'Hirata, Yukiyo', 'Takizawa, Hajime', 'Azuma, Arata', 'Yamamoto, Masayuki', 'Kawada, Tomoyuki', 'Kim, Min-Gu', 'Hong, Gyong Hwa', 'Lee, Kyoung Young', 'Ha, Eun Hee', 'Moon, Keun Ai', 'Park, Sunjoo', 'Kwon, Hyouk-Soo', 'Kim, Tae-Bum', 'Moon, Hee-Bom', 'Cho, You Sook', 'Kim, Jung-Hyun', 'Kim, Hyo-Jung', 'Park, So-Young', 'Seo, Bomi', 'Kim, Ji-Hye', 'Samivel, Ramachandran', 'Kim, Eun-Hee', 'Chung, Young-Jun', 'Mo, Ji-Hun', 'Soumya, M. S.', 'Inbaraj, G.', 'Chellaa, R.', 'Pawankar, Ruby', 'Choi, Wonsun', 'Park, Hae-Sim', 'Ye, Young Min', 'Kim, Ji Hye', 'Ban, Ga Young', 'Shin, Yoo-Seob', 'Braber, Saskia', 'Verheijden, Kim', 'Kraneveld, Aletta', 'Garssen, Johan', 'Folkerts, Gert', 'Willemsen, Linette', 'Eichhorn, Stephanie', 'Ferreira, Fatima', 'Pablos, Isabel', 'Kastner, Bianca', 'Schweidler, Bettina', 'Wildner, Sabrina', 'Briza, Peter', 'Park, Jung-Won', 'Arora, Naveen', 'Vieths, Stefan', 'Gadermaier, Gabriele', 'Park, Sung-Min', 'Lee, Won-Ku', 'Kim, Jeong-Min', 'Kim, Gun-Wook', 'Mun, Je-Ho', 'Kim, Hoon-Soo', 'Song, Margaret', 'Ko, Hyun-Chang', 'Kim, Moon-Bum', 'Kim, Byung Soo', 'Kim, Young Nam', 'Yune, Sehyo', 'Lee, Jin-Young', 'Kim, Jihye', 'Kim, Young Eun', 'Paeng, Jae-Won', 'Jang, Mi-Jin', 'Choi, Dong-Chull', 'Lee, Byung-Jae', 'Lee, Yongseok', 'Goh, Si Hui', 'Lee, Bee Wah', 'Soh, Jian Yi', 'Kang, Hyungoo', 'Kim, Hyunhee', 'Yum, Hye-Yung', 'Ye, Young Min', 'Park, Hae-Sim', 'Ban, Ga-Young', 'Kim, Ji Hye', 'Shin, Yoo Seob', 'Takizawa, Takumi', 'Tabata, Masahiko', 'Aizawa, Akira', 'Yagi, Hisako', 'Nishida, Yutaka', 'Arakawa, Hirokazu', 'Morikawa, Akihiro', 'Orosoo, Solongo', 'Braber, Saskia', 'Bol-Schoenmakers, Marianne', 'Akbari, Peyman', 'Jeurink, Prescilla V.', 'Jeurink, Prescilla V.', 'De Graaff, Priscilla', 'Smit, Joost J.', 'Van Esch, Betty C. A. M.', 'Garssen, Johan', 'Garssen, Johan', 'Fink-Gremmels, Johanna', 'Pieters, Raymond H. H.', 'Kim, Gun-Woo', 'Jo, Eun-Jung', 'Kim, Sujeong', 'Song, Woo-Jung', 'Chang, Yoon-Seok', 'Faruqi, Shoaib', 'Kim, Ju-Young', 'Kang, Mingyu', 'Kim, Min-Hye', 'Plevkova, Jana', 'Park, Heung Woo', 'Cho, Sang-Heon', 'Morice, Alyn', 'Lee, So-Hee', 'Kim, Sun-Sin', 'Lee, Seoung-Eun', 'Gemicioglu, Bilun', 'Misirligil, Zeynep', 'Cimrin, Arif Hikmet', 'Gunen, Hakan', 'Ozlu, Tevfik', 'Cilli, Aykut', 'Akyildiz, Levent', 'Bayram, Hasan', 'Uzaslan, Esra', 'Abadoglu, Oznur', 'Suerdem, Mecit', 'Kainuma, Keigo', 'Kim, Hyun-a', 'Kim, Ha-Su', 'Bae, Woo Yong', 'Jung, Jin-a', 'Kamenwa, Rose', 'Macharia, William', 'Said, Nusrat', 'Nerurkar, Vidya', 'Patel, Meenal', 'Bhatia, Simi', 'Choi, Inseon S.', 'Kim, Soo-Jeong', 'Won, Joo-Min', 'Park, Myeong-Soo', 'Nagao, Mizuho', 'Park, Dong Won', 'Sohn, Jang Won', 'Yhi, Ji Young', 'Moon, Ji-Yong', 'Kim, Sang-Heon', 'Kim, Tae Hyung', 'Shin, Dong Ho', 'Yoon, Ho Joo', 'Hyo, Yukiyoshi', 'Lee, Jaechun', 'Kim, Su Hee', 'Lee, Eunkyoung', 'Jung, Hahn Jin', 'Lim, Jaehyun', 'Hong, Seung-No', 'Han, Doo Hee', 'Rhee, Chae-Seo', 'Lee, Kun Song', 'Lee, Jaechun', 'Yang, Sun Young', 'Ahn, Mi Young', 'Lee, Jong Hoo', 'Golez, Jasmina', 'Tian, Hui-Qin', 'Cheng, Lei', 'Chen, Xin-Yuan', 'Moon, Ji-Yong', 'Kim, Sang-Heon', 'Kim, Tae Hyung', 'Yhi, Ji Young', 'Yoon, Ho Joo', 'Sohn, Jang Won', 'Shin, Dong Ho', 'Park, Dong Won', 'Cho, Won Im', 'Choi, Jong Sub', 'Suh, Dongin', 'Kang, Gyeong Hoon', 'Moon, Jin Soo', 'Ko, Jae Sung', 'Lee, Kyung Jae', 'Choi, Shin Jie', 'Luo, Wenting', 'Sun, Baoqing', 'Gao, Qi', 'Xiang, Li', 'Shen, Kunling', 'Jang, Yong Hyun', 'Bergmann, Karl-Christian', 'Sehlinger, Torsten', 'Bölke, Georg', 'Berger, Uwe', 'Zuberbier, Torsten', 'Kolodziejczyk, Joanna', 'Wojciechowska, Milena', 'Hnatyszyn-Dzikowska, Anna', 'Chojnacki, Micha', 'Bartuzi, Zbigniew', 'Masaki, Katsunori', 'Fukunaga, Koichi', 'Kamatani, Takashi', 'Ohtsuka, Kengo', 'Tanosaki, Takae', 'Matsusaka, Masako', 'Mochimaru, Takao', 'Kabata, Hiroki', 'Ueda, Soichiro', 'Suzuki, Yusuke', 'Kamei, Katsuhiko', 'Asano, Koichiro', 'Betsuyaku, Tomoko', 'Trafford, Karlee', 'Bulut, Ismet', 'Ozseker, Zeynep Ferhan', 'Horimukai, Kenta', 'Morita, Hideaki', 'Narita, Masami', 'Niizeki, Hironori', 'Matsumoto, Kenji', 'Ohya, Yukihiro', 'Saito, Hirohisa', 'Kabashima, Shigenori', 'Kondo, Mai', 'Inoue, Eisuke', 'Siebers, Robert', 'Wu, Francis F. S.', 'Siebers, Robert', 'Wu, Francis F. S.', 'Ting, Ming-Hui', 'Laio, Hung-En', 'Kuo, Tsung-Huai', 'Lee, Pei-Yuan', 'Maddox, Daniel Eugene', 'Ryu, Gwanghui', 'Kim, Hyo Yeol', 'Dhong, Hun-Jong', 'Hong, Sang Duk', 'Chung, Seung-Kyu', 'Higuchi, Osamu', 'Adachi, Yu-Ichi', 'Itazawa, Toshiko', 'Adachi, Yoko', 'Hamamichi, Miki', 'Nakabayashi, Motokazu', 'Ito, Yasunori', 'Wada, Takuya', 'Murakami, Gyoukei', 'Takao, Miki', 'Yamamoto, Junko', 'Jin, Hyun Jung', 'Yoon, Moon Gyeong', 'Ye, Young Min', 'Shin, Yoo-Seob', 'Kim, Seung-Hyun', 'Park, Hae-Sim', 'Min, Taek-Ki', 'Pyun, Bok-Yang', 'Lee, So-Yeon', 'Kim, Hyun Hee', 'Jang, Gwang-Cheon', 'Yu, Jinho', 'Suh, Dongin', 'Lee, Sooyoung', 'Park, Yong Mean', 'Kim, Jeong Hee', 'Yum, Hye-Yung', 'Kim, Kyung Won', 'Yang, Hyeon-Jong', 'Ahn, Kangmo', 'Kwon, Ji-Won', 'Sohn, Myung Hyun', 'Lee, Hae Ran', 'Kwon, Jung Hyun', 'Kim, Kyu-Earn', 'Hong, Soo-Jong', 'Cho, Su-Mi', 'Nahm, Dong-Ho', 'Kim, Myoung-Eun', 'Lee, Jin Hwa', 'Rhee, Chin Kook', 'Park, Hye Yun', 'Kim, Woo Jin', 'Park, Yong Bum', 'Yoo, Kwang-Ha', 'Kang, Heejeong', 'Yang, Hyeon-Jong', 'Min, Taek-Ki', 'Pyun, Bok-Yang', 'Suk, Lee Ju', 'Kim, Cheol Hong', 'Kwon, Jung Hyun', 'Lee, Sang Hyun', 'Seo, Wonhee', 'Kim, Kang-in', 'Park, Young Cheon', 'Yang, Hyeon-Jong', 'Min, Taek-Ki', 'Pyun, Bok-Yang', 'Kim, Sujeong', 'Jin, Sun', 'Lee, Jong-Myung', 'Jung, Hye-Jin', 'Park, Jung-Wha', 'Kim, Hyo-Jung', 'Kim, Tae-Bum', 'Cho, You Sook', 'Moon, Hee-Bom', 'Kwon, Hyouk-Soo', 'Park, So Young', 'Park, So-Young', 'Kim, Jung-Hyun', 'Seo, Bomi', 'Kim, Min-Gu', 'Kim, Youn Yee', 'Lee, Yena', 'Min, Taek-Ki', 'Yang, Hyeon-Jong', 'Pyun, Bok-Yang', 'Han, Suk Hee', 'Park, Suyeon', 'Lee, Jeongho', 'Hahn, Won-Ho', 'Jeon, Youhoon', 'Kim, Joo-Hee', 'Shin, Tae-Rim', 'Kim, Cheol-Hong', 'Hyun, In-Gyu', 'Choi, Jeong-Hee', 'Jang, Sun-Mi', 'Na, Hae-Jung', 'Song, Seung-Eon', 'Park, Hye-Kyung', 'Jo, Eun-Jung', 'Lee, Dong Hun', 'Lee, Jin-Young', 'Park, Yang', 'Oh, Jae-Won', 'Lee, Mi Hee', 'Hong, Soo-Jong', 'Hong, Soo-Jong', 'Lee, So-Yeon', 'Park, Joon Soo', 'Nahm, Dong-Ho', 'Yum, Hye-Yung', 'Yum, Hye-Yung', 'Choi, Kyu Young', 'Kim, Dong-Young', 'Palapinyo, Sirinoot', 'Klaewsongkram, Jettanong', 'Chen, Xing', 'Jin, Yuting', 'Hou, Xiaoming', 'Liu, Fengqin', 'Guo, Chunyan', 'Wang, Yulin', 'Okafuji, Ikuo', 'Tanaka, Yuya', 'Narabayashi, Shegeyuki', 'Tsuruta, Satoru', 'Jang, Yong Hyun', 'Ahn, Jun-Hong', 'Lee, Dong-Won', 'Chung, Jin Hong', 'Jin, Hyun Jung', 'Sohn, Min-Su', 'Park, Young a', 'Jeong, Kyunguk', 'Kim, Yoon Hee', 'Sol, In Suk', 'Yoon, Seo Hee', 'Kim, Kyung Won', 'Sohn, Myung Hyun', 'Kim, Kyu-Earn', 'Lee, Sooyoung', 'Kim, Ho', 'Kim, Ja Yeun', 'Lee, So-Yeon', 'Min, Taek-Ki', 'Song, Tae-Won', 'Ahn, Kangmo', 'Kim, Jihyun', 'Jang, Gwang-Cheon', 'Yang, Hyeon-Jong', 'Pyun, Bok-Yang', 'Kwon, Ji-Won', 'Sohn, Myung Hyun', 'Kim, Kyu-Earn', 'Yu, Jinho', 'Hong, Soo-Jong', 'Kwon, Jung-Hyun', 'Kim, Sung-Won', 'Lee, Sooyoung', 'Kim, Woo Kyung', 'Kim, Hyung Young', 'Kim, Hye-Young', 'Jeon, Youhoon', 'Lim, Chang Hoon', 'Jeong, Yeongsang', 'Kim, Su Jung', 'Chang, Hun Soo', 'Heo, Jeong-Seok', 'Bae, Da-Jeong', 'Lee, Jong-Uk', 'Kim, Ji-Na', 'Min, Chang-Gi', 'Song, Hyun Ji', 'Park, Jong-Sook', 'Kim, Soo Hyun', 'Park, Choon-Sik', 'Liu, Jing-Nan', 'Choi, Youngwoo', 'Shin, Yoo Seob', 'Park, Hae-Sim', 'Rezaei, Nima', 'Mahneh, Sedigheh Bahrami', 'Rezaei, Arezou', 'Sadr, Maryam', 'Movahedi, Masoud', 'Gang, Jun Seak', 'Park, Joon Soo', 'Kim, Seung Soo', 'Bang, Hyun Ho', 'Park, Kyeong Bae', 'Kim, Hye Sun', 'Kim, Tae Ho', 'Hwangbo, Young', 'Lee, Hyun Jung', 'Yoo, Gyeong Hee', 'Kim, Young Chang', 'Sato, Sakura', 'Yanagida, Noriyuki', 'Ebisawa, Motohiro', 'Palikhe, Sailesh', 'Park, Hae-Sim', 'Kim, Seung-Hyun', 'Kim, Ri-Yeon', 'Yang, Eun-Mi', 'Lee, Li Yuan Gabriella Nadine', 'Aw, Marion', 'Aw, Marion', 'Lee, Bee Wah', 'Lee, Bee Wah', 'Loo, Evelyn Xiu Ling', 'Chan, Yiong Huak', 'Shek, Lynette', 'Shek, Lynette', 'Kuo, I-Chun', 'Kuo, I-Chun', 'Quah, Phaik Ling', 'Quah, Phaik Ling', 'Llanora, Genevieve', 'Irvin, Gerez', 'Jung, Joo Hyun', 'Kang, Il Gyu', 'Kim, Seon Tae', 'Park, Hyoungmin', 'Kim, Seon Tae', 'Jung, Joo Hyun', 'Kang, Il Gyu', 'Park, Hyoungmin', 'Ko, Kwang-Pil', 'Lee, Jungsoo', 'Chu, Howard', 'Lee, Hemin', 'Shin, Jung U.', 'Park, Chang Ook', 'Lee, Kwang Hoon', 'Lee, Kwang Hoon', 'Kang, Hong Kyu', 'Lee, Dong Chang', 'Kim, Geun Jeon', 'Hwang, Jae Hyung', 'Ha, Jin Bu', 'Jeong, Su Hee', 'Kim, Ho', 'Hwang, Shinha', 'Lee, Whahee', 'Bazarsad, Enkhbayar', 'Narantsetseg, Logii', 'Sonomjamts, Munkhbayarlakh', 'Jang, Gwang-Cheon', 'Lee, Hyun-Hee', 'Lee, Chang-Jong', 'Lim, Huynsun', 'Soh, Ji-Eun', 'Song, Dae-Jin', 'Kwon, Ji-Won', 'Kim, Hyung Young', 'Seo, Ju-Hee', 'Kim, Byoung-Ju', 'Kim, Hyo-Bin', 'Lee, So-Yeon', 'Jang, Gwang-Cheon', 'Kim, Woo Kyung', 'Jung, Young-Ho', 'Hong, Soo-Jong', 'Shim, Jung Yeon', 'Bazarsad, Enkhbayar', 'Narantsetseg, Logii', 'Sonomjamts, Munkhbayarlakh', 'Pv, Prabhakarrao', 'Nadendla, Ranjitha', 'Fang, Juan', 'Zhao, Jing', 'Song, Dae-Jin', 'Seo, Sungchul', 'Yoo, Young', 'Kim, Yu-Ri', 'Choung, Ji Tae', 'Lee, Jee Hoo', 'Berings, Margot', 'De Ruyck, Natalie', 'Bachert, Claus', 'Gevaert, Philippe', 'Holtappels, Gabriële', 'Lee, Pureun-Haneul', 'Kim, Byeong-Gon', 'Park, Choon-Sik', 'Leikauf, George D.', 'Jang, An-Soo', 'Kimc, Byeong-Gon', 'Lee, Pureun-Haneul', 'Park, Choon-Sik', 'Jang, An-Soo', 'Park, Yang', 'Sohn, Min-Su', 'Jin, Hyun Jung', 'Lee, Dong-Won', 'Ahn, Jun-Hong', 'Chung, Jin Hong', 'Kim, Sae-in', 'Park, Han-Ki', 'Kim, Do-Yeon', 'Rho, Mina', 'Choi, Jun-Pyo', 'Kim, Yoon-Keun', 'Kamchaisatian, Wasu', 'Hiranras, Thitikul', 'Wongpun, Surinda', 'Chiraphorn, Phornthip', 'Tantachun, Anupan', 'Wongrassamee, Wannipa', 'Vatanasurkitt, Planee', 'Somboonkul, Naratip', 'Juthacharoenwong, Nattipat', 'Techapaitoon, Surangkana', 'Tuchinda, Montri', 'An, Sejin', 'Lee, Jae Ho', 'Shin, Ji-Hyeon', 'Kim, Soo Whan', 'Kim, Si Won', 'Kang, Jun Myung', 'Kim, Boo-Young', 'Kim, Byung-Guk', 'Kwon, Ji-Won', 'Kim, Woo Kyung', 'Kim, Hyung Young', 'Kim, Hyo-Bin', 'Seo, Ju-Hee', 'Lee, So-Yeon', 'Jang, Gwang-Cheon', 'Jung, Young-Ho', 'Hong, Soo-Jong', 'Kim, Byoung-Ju', 'Song, Dae-Jin', 'Shim, Jung Yeon', 'Lee, Jung-Won', 'Kim, Kyung Ho', 'Yoo, Young', 'Yoon, Won Suck', 'Seo, Sungchul', 'Kang, In Soon', 'Choi, Jae Won', 'Lim, Hye-Young', 'Choung, Ji Tae', 'Buela, Michelle', 'Nishimura, Koji', 'Park, Sang Chul', 'Chung, Hyo Jin', 'Kim, Chang-Hoon', 'Kang, Ju Wan', 'Hong, Seong-Chul', 'Lee, Keun-Hwa', 'Lee, Jaechun', 'Lee, Hye-Sook', 'Kim, Jeong Hong', 'Logii, Narantsetseg', 'Nyamdavaa, N.', 'Enkhbayar, B.', 'Oyuntsatsral, B.', 'Munkhbayarlakh, S.', 'Bazarsad, Enkhbayar', 'Sonomjamts, Munkhbayarlakh', 'Omarjee, Bashir', 'Li, Shuo', 'Hayashi, Miyuki', 'Pawankar, Ruby', 'Yamanishi, Shingo', 'Igarashi, Toru', 'Itoh, Yasuhiko', 'Gantulga, B.', 'Enkhbayar, B.', 'Munkhbayarlakh, S.', 'Narantsetseg, L.', 'Batsaikhan, Oyuntsatsral', 'Chen, Pei-Chi', 'Wang, Jiu-Yao', 'Leung, Nicki Y. H.', 'Wai, Christine Yee Yan', 'Leung, Patrick S. C.', 'Chu, Ka Hou', 'Doh, Eun Jin', 'Lee, Dong Hun', 'Choi, Mira', 'Yoon, Hyun-Sun', 'Kim, Kyu Han', 'Lim, Ji Soo', 'Baek, Ji Hyeon', 'Han, Man Yong', 'Lee, Seung Jin', 'Jeon, Youhoon', 'Lee, Kyung Suk', 'Jung, Young-Ho', 'Jee, Hye Mi', 'Shin, Youn Ho', 'Jiang, Yi', 'Liu, Miao', 'Naing, Chaw Su', 'Tan, Tze Chin', 'Chong, Yong Yeow', 'Kim, Young-Ho', 'Lee, Eun', 'Yang, Song-I', 'Cho, Hyun-Ju', 'Kim, Hyung Young', 'Kwon, Ji-Won', 'Jung, Young-Ho', 'Kim, Byoung-Ju', 'Seo, Ju-Hee', 'Kwon, Ho-Jang', 'Kim, Hyo-Bin', 'Lee, So-Yeon', 'Hong, Soo-Jong', 'Kim, Soo Hyun', 'Joseph, Jacqueline Elizabeth', 'Soumya, M. S.', 'Pawankar, Ruby', 'Kumar, Harshitha', 'Yang, Sohyoung', 'Woo, Sung-Il', 'Rezaei, Nima', 'Kose, Sukran', 'Serin, Basak Gol', 'Yalcin, Arzu Didem', 'Senger, Süheyla Serin', 'Erden, Mehmet', 'Serin, Ertan', 'Leung, Ting Fan', 'Leung, Agnes Sze-Yin', 'Kumar, Harshitha', 'Soumya, M. S.', 'Joseph, Jacqueline Elizabeth', 'Pawankar, Ruby', 'Chung, Eun Hee', 'Kim, Eunji', 'Yoo, Young', 'Yoo, Young', 'Choung, Ji Tae', 'Choung, Ji Tae', 'Seo, Sungchul', 'Seo, Sungchul', 'Kang, In Soon', 'Lee, Jue Seong', 'Hwang, Ji Hyen', 'Lee, Sang Min', 'Jung, Joo Hyun', 'Choi, Seung Joon', 'Joe, Eugene', 'Hwang, Hyunjung', 'Kang, Shin Myung', 'Kim, Yu Jin', 'Kyung, Sun Young', 'Park, Jeong-Woong', 'Jeong, Sung Hwan', 'Lee, Sang Pyo', 'Gaisina, Alina', 'Shilovskiy, Igor', 'Nikonova, Aleksandra', 'Kamyshnikov, Oleg', 'Khaitov, Musa', 'Mitin, Alexander', 'Viktoriya, Komogorova', 'Litvina, Marina', 'Sharova, Nina', 'Faiah, M. J.', 'Ismail, Intan H.', 'Miles, E. A.', 'Jamli, Faizah Mohamed', 'Choi, Jun-Pyo', 'Choi, Han-Byul', 'Kim, Yoon-Keun', 'Choi, Hyeon-Il', 'Yoon, Da-Il', 'Kang, Mingyu', 'Kim, Mi Yeoung', 'Kim, Sujeong', 'Jo, Eun-Jung', 'Lee, Seoung-Eun', 'Song, Woo-Jung', 'Lee, Sang Min', 'Park, Chansun', 'Chang, Yoon-Seok', 'Lee, Jaechun', 'Jee, Young-Koo', 'Choi, Inseon S.', 'Min, Kyung-up', 'Cho, Sang-Heon', 'Cho, Sang-Heon', 'Laskin, Anton', 'Kamyshnikov, Oleg', 'Babakhin, Alexander', 'Berzhets, Valentina', 'Khaitov, Musa', 'Lee, Jae Ho', 'An, Sejin', 'Chang, Yoon-Seok', 'Min, Kyung-up', 'Cho, Sang-Heon', 'Kim, Sae-Hoon', 'Kwon, Yong Eun', 'Jee, Young-Koo', 'Kim, Tae-Bum', 'Moon, Hee-Bom', 'Park, Hye-Kyung', 'Kang, Sung-Yoon', 'Choi, Jun-Pyo', 'Park, Han-Ki', 'Lee, Ji-Hyun', 'Kim, Yoon-Keun', 'Kim, Sang-Yoon', 'Hwang, Hyunjung', 'Joe, Eugene', 'Lee, Sang Min', 'Choi, Seung Joon', 'Jung, Joo Hyun', 'Seon, Yong Han', 'Kang, Shin Myung', 'Kim, Yu Jin', 'Kyung, Sun Young', 'Park, Jeong-Woong', 'Jeong, Sung Hwan', 'Lee, Sang Pyo', 'Khramykhoverchenko, Natalya', 'Sultana, Asma', None, 'Halwani, Rabih', 'Bahammam, Ahmed', 'Al Muhsen, Saleh', 'Kim, Sun Kyung', 'Nam, Kwang Il', 'Yang, Hyung Chae', 'Kim, Jeong-Eun', 'Lee, Ju Suk', 'Lee, Ji Hyun', 'Kang, Kyung Woo', 'Kim, Je-Kyung', 'Hahn, Youn-Soo', 'Jung, Jae-Yub', 'Baba, Yosuke', 'Yamazaki, Sususmu', 'Inage, Eisuke', 'Mori, Mari', 'Ohtsuka, Yoshikazu', 'Kantake, Masato', 'Shimizu, Toshiaki', 'Honjoh, Asuka', 'Yokokura, Tomoaki', 'Elhassan, Shaza Ali Mohammed', 'Beck, Caroline', 'Adeli, Mehdi', 'Baek, Heysung', 'Lee, Seung Jin', 'Baek, Ji Hyeon', 'Yoon, Jungwon', 'Choi, Sun Hee', 'Jung, Young-Ho', 'Shin, Youn Ho', 'Han, Man Yong', 'Na, Min Sun', 'Compalati, Enrico', 'Marogna, Maurizio', 'Huang, Huimin', 'Sun, Baoqing', 'Bai, Mingyu', 'Huo, Yiting', 'Zheng, Peiyan', 'Wei, Nili', 'Luo, Wenting', 'Andiappan, Anand', 'Minisini, Rosalba', 'Rötzschke, Olaf', 'Boggio, Elena', 'Gigliotti, Luca', 'Clemente, Nausicaa', 'Chiocchetti, Annalisa', 'Dianzani, Umberto', 'Pirisi, Mario', 'Villa, Elisa', 'Yamaide, Fumiya', 'Yonekura, Syuji', 'Shimojo, Naoki', 'Inoue, Yuzaburo', 'Okamoto, Yoshitaka', 'Setyoningrum, Retno Asih', 'Setiawati, Landia', 'Sumei, Sri', 'Iskandar, Deddy', 'Kompiyang, Indriyani Sang Ayu', 'Oguma, Tsuyoshi', 'Tanaka, Jun', 'Tomomatsu, Katsuyoshi', 'Asano, Koichiro', 'Uno, Keisuke', 'Matsuwaki, Yoshinori', 'Omura, Kazuhiro', 'Hayashi, Eika', 'Tatsumi, Norifumi', 'Kita, Hirohito', 'Otori, Nobuyoshi', 'Kojima, Hiromi', 'Khorasgani, Mohammadreza Fatemi', 'Lew, Dukhee/Betty', 'Lemessurier, Kim/S.', 'Moore, Joseph/a', 'Park, Jeoung-Eun', 'Yi, Ae-Kyung', 'Song, Chi/Young', 'Malik, Kafait/U', 'Kim, Ja Kyoung', 'Yang, Hyeon-Jong', 'Kim, Bong-Seong', 'Shin, Youn Ho', 'Lee, So-Yeon', 'Park, Geunhwa', 'Kim, Woo Kyung', 'Kim, Hyo-Bin', 'Baek, Heysung', 'Lim, Dae Hyun', 'Lim, Dae Hyun', 'Kim, Jin Tack', 'Suh, Dongin', 'Nano, Aimee Lou Manalo', 'Sun, Baoqing', 'Luo, Wenting', 'Nacaroglu, Hikmet Tekin', 'Erdem, Semiha Bahceci', 'Sumer, Ozlem', 'Karaman, Sait', 'Karkiner, Canan Sule Unsal', 'Asilsoy, Suna', 'Gunay, Ilker', 'Can, Demet', 'Kiers, Danielle', 'Wang, Jiu-Yao', 'Yin, Hsu Han', 'Kaplan, Allen', 'Joseph, Kusumam', 'Tholanikunnel, Baby G.', 'Dudek, Radim', 'Bilgin, Gulden', 'Surer, Hatice', 'Kilinc, Aytun Sadan', 'Yucel, Dogan', 'Lee, Ji Young', 'Kim, Jihyun', 'Yang, Hea-Kyoung', 'Kim, Minji', 'Lee, Sang-Il', 'Ahn, Kangmo', 'Moon, Sung Do', 'Kim, Byung-Keun', 'Cho, Sang-Heon', 'Min, Kyung-up', 'Chang, Yoon-Seok', 'Park, Heung Woo', 'Kang, Hye-Ryun', 'Song, Woo-Jung', 'Kang, Min-Koo', 'Kim, Ju-Young', 'Sohn, Kyonghee', 'Won, Ha Kyung', 'Lee, Seoung-Eun', 'Kim, Kyung-Mook', 'Bachert, Claus', 'Hsieh, Miao-Hsi', 'Wang, Jiu-Yao', 'Smith, Helen', 'Brown, Clare', 'Jones, Christina', 'Davies, Mark', 'Yoon, Won Suck', 'Lee, Hemin', 'Chu, Howard', 'Lee, Jungsoo', 'Shin, Jung U.', 'Park, Chang Ook', 'Lee, Kwang Hoon', 'Lee, Kwang Hoon', 'Kim, Seo Hyeong', 'Kim, Seo Hyeong', 'Noh, Ji Yeon', 'Kim, Ji Hye', 'Kim, Ji Hye', 'Yoon, Won Suck', 'L’huillier, Jean-Pierre', 'Autegarden, Jean-Eric', 'Bertrand, Catherine', 'Tardy, Dominique', 'Ismail, Intan Hakimah', 'Tang, Mimi', 'Licciardi, Paul', 'Oppedisano, Frances', 'Boyle, Robert', 'Robins-Browne, Roy', 'Yagi, Hisako', 'Koyama, Harumi', 'Nishida, Yutaka', 'Takizawa, Takumi', 'Arakawa, Hirokazu', 'Kang, Hong Kyu', 'Lee, Hemin', 'Lee, Jungsoo', 'Shin, Jung U.', 'Lee, Kwang Hoon', 'Lee, Kwang Hoon', 'Chu, Howard', 'Park, Chang Ook', 'Yoon, Na Young', 'Lee, Hyeyoung', 'Seo, Seong Jun', 'Choi, Eunhee', 'Wang, Hye-Young', 'Jung, Minyoung', 'Choi, Eung Ho', 'Kim, Dong Hye', 'Kim, Joo-Hee', 'Jang, Young-Sook', 'Choi, Jeong-Hee', 'Park, Sunghoon', 'Hwang, Young Il', 'Jang, Seung Hun', 'Jung, Ki-Suck', 'Kang, Mi-Jin', 'Suh, Dongin', 'Lee, Eun', 'Choi, Kil Yong', 'Jung, Young-Ho', 'Yang, Song-I', 'Kim, Bong-Soo', 'Kim, Ha-Jung', 'Koh, Juneyoung', 'Kim, Hyun-Jin', 'Ahn, Kangmo', 'Shin, Youn Ho', 'Cho, Hyun-Ju', 'Kim, Byoung-Ju', 'Kim, Young-Ho', 'Jung, Yean', 'Mamura, Mizuko', 'Yoon, Jeong-Hwan', 'Nakae, Susumu', 'Lee, Inkyu', 'Matsumoto, Isao', 'Sumida, Takayuki', 'Han, Jin Soo', 'Sudo, Katsuko', 'Ju, Ji Hyeon', 'Yap, Gaik Chin', 'Liu, Wen Tso', 'Oh, Seungdae', 'Hong, Pei Ying', 'Huang, Chiung Hui', 'Aw, Marion', 'Shek, Lynette', 'Lee, Bee Wah', 'Byun, Young Seok', 'Kim, Sung Wan', 'Koh, Tae Kyung', 'Jo, Joong-Saeng', 'Lee, Kun Hee', 'Kwon, Chul', 'Dong, Sung-Hwa', 'Kim, Myung Shin', 'Park, Chansun', 'Cho, Han Seok', 'Kim, Min-Ju', 'Kim, Min Ji', 'Park, Young Ok', 'Lee, Hye Yeong', 'Kim, Hee Seong', 'Lee, Eun', 'Cho, Hyun-Ju', 'Yu, Jinho', 'Hong, Soo-Jong', 'Hwang, Keum Hee', 'Kim, Jung-Hyun', 'Cho, You Sook', 'Kim, Sae-Hoon', 'Kwon, Hyouk-Soo', 'Yoo, Mira', 'Kim, Hyo-Jung', 'Park, So-Young', 'Shin, Bomi', 'Park, So Young', 'Seo, Bomi', 'Kim, Min-Gu', 'Moon, Hee-Bom', 'Park, Jin-Ah', 'Kim, Tae-Bum', 'Lee, Jaemoon', 'Jeong, Jin Hyeok', 'Kang, Tae Wook', 'Yoo, Han Seok', 'Cho, Yong Hee', 'Cho, Seok Hyun', 'Kim, Kyung Rae', 'Lee, Jue Seong', 'Kee, Sun-Ho', 'Kim, Sewon', 'Yoo, Young', 'Na, Heung Sik', 'Back, Seung Keun', 'Lee, Seung Jin', 'Seo, Bo Seon', 'Baek, Ji Hyeon', 'Lee, Kyung Suk', 'Jung, Young-Ho', 'Jee, Hye Mi', 'Shin, Youn Ho', 'Han, Man Yong', 'Kim, Mi-Ae', 'Nam, Young-Hee', 'Jeon, Dong Sub', 'Lee, Soo-Keol', 'Park, Jisun', 'Moon, Seung Hyun', 'Lin, Rong Jun', 'Guan, Ren Zheng', 'Park, Gyeong Yul', 'Yoon, Hyun-Sun', 'Choi, Woo-Hyeok', 'Baek, Heysung', 'Park, Jin-Sung', 'Kwon, Eunmi', 'Callaway, Zac', 'Kim, Chang-Keun', 'Fujisawa, Takao', 'Zhang, Qingling', 'Qiu, Rihuang', 'Li, Naijian', 'Yang, Zhaowei', 'Li, Jing', 'Chung, Kian Fan', 'Zhong, Nanshan', 'Hon, Kam Lun E.', 'Tsang, Yin Ching K.', 'Leung, Ting Fan', 'Jang, Yoon Young', 'Chung, Hai Lee', 'Lee, Seung Gook', 'Na, Ji Hyun', 'Lee, Jong Hoon', 'Nam, Young-Hee', 'Jeon, Dong Sub', 'Lee, Soo-Keol', 'Yamamoto, Mikita', 'Sato, Sakura', 'Yanagida, Noriyuki', 'Ogawa, Ayako', 'Ogura, Kanako', 'Takahashi, Kyohei', 'Nagakura, Kenichi', 'Emura, Shigehito', 'Asaumi, Tomoyuki', 'Iikura, Katsuhito', 'Ebisawa, Motohiro', 'Okada, Yu', 'Luo, Jiaying', 'Lan, Xiao', 'Sun, Baoqing', 'Chen, Zhao', 'Sun, Guiyuan', 'Li, Shimin', 'Hu, Jiaqing', 'Choi, Woo-Hyeok', 'Baek, Heysung', 'Nam, Young-Hee', 'Jeon, Dong Sub', 'Nam, Hee-Joo', 'Noh, Yeo Myeong', 'Kim, Sang Hee Kim', 'Park, Ye Suel', 'Lee, Soo-Keol', 'Choi, Yean Jung', 'Lee, Si Hyeon', 'Kim, Young-Ho', 'Kang, Mi-Jin', 'Cho, Hyun-Ju', 'Lee, Eun', 'Yang, Song-I', 'Shin, Youn Ho', 'Ahn, Kangmo', 'Kim, Kyung Won', 'Kim, Yoon Hee', 'Lee, So-Yeon', 'Chang, Hyoung Yoon', 'Choi, In Ae', 'Lee, Kyung-Sook', 'Shin, Yee-Jin', 'Kim, Yoon Hee', 'Kim, Min Jung', 'Sol, In Suk', 'Yoon, Seo Hee', 'a Park, Young', 'Kim, Kyung Won', 'Sohn, Myung Hyun', 'Kim, Kyu-Earn', 'Lee, Yong Ju', 'Sol, In Suk', 'Kim, Kyu-Earn', 'Kim, Yoon Hee', 'Kim, Min Jung', 'Yoon, Seo Hee', 'Lee, Yong Ju', 'Kim, Kyung Won', 'a Park, Young', 'Sohn, Myung Hyun', 'Park, Sung Joo', 'Kwon, Ji-Won', 'Kim, Woo Kyung', 'Kim, Hyung Young', 'Kim, Hyo-Bin', 'Seo, Ju-Hee', 'Lee, So-Yeon', 'Jang, Gwang-Cheon', 'Jung, Young-Ho', 'Hong, Soo-Jong', 'Kim, Byoung-Ju', 'Song, Dae-Jin', 'Yang, Yun Seok', 'Shim, Jung Yeon', 'Jang, Yoon Young', 'Chung, Hai Lee', 'Kim, Ji Hye', 'Lee, Hyun Seok', 'Lee, Chang Ho', 'Cho, Changbum', 'Lim, Yun-Kyu', 'Kim, Kyu Rang', 'Kim, Mijin', 'Kim, Baek-Jo', 'Kim, Young-Min', 'Han, Youngshin', 'Kim, Jihyun', 'Cheong, Hae-Kwan', 'Jeon, Byoung-Hak', 'Ahn, Kangmo', 'Ming, Chuang/Yao', 'Wang, Jiu-Yao', 'Ling, Ye/Yi', 'Huang, Huimin', 'Sun, Baoqing', 'Chen, Yun', 'Zheng, Peiyan', 'Wei, Nili', 'Luo, Wenting', 'Lee, Do Hyeong', 'Choi, Gil-Soon', 'Kim, Hee-Kyoo', 'Park, Han Su', 'Park, So-Young', 'Kim, Hyo-Jung', 'Seo, Bomi', 'Kim, Jung-Hyun', 'Kim, Min-Gu', 'Kwon, Hyouk-Soo', 'Cho, You Sook', 'Moon, Hee-Bom', 'Kim, Tae-Bum', 'Lee, Yoon Su', 'Shin, Eun-Soon', 'Tanaka, Akio', 'Morioke, Satoshi', 'Ohya, Yukihiro', 'Shimojo, Naoki', 'Akasawa, Akira', 'Hide, Michihiro', 'Shizukawa, Hiroko', 'Watanabe, Naoto', 'Shin, Meeyong', 'Jang, Myeong Sun', 'Nam, Young-Hee', 'Noh, Yeo Myeong', 'Jeon, Dong Sub', 'Nam, Hee-Joo', 'Kim, Sang Hee Kim', 'Park, Ye Suel', 'Lee, Soo-Keol', 'Jung, Ji-in', 'Kim, Ha-Su', 'Kim, Hyun-a', 'Jung, Jin-a', 'Goh, Anne', 'Rao, Rajeshwar', 'Nandanan, Bindu', 'Van Elburg, Ruurd', 'Chien, Chua Mei', 'Jo, Juandy', 'Garssen, Johan', 'Garssen, Johan', 'Knippels, Leon', 'Sandalova, Elena', 'Chiang, Wen Chin', 'Nam, Young-Hee', 'Juong, Ji Young', 'Kim, Soo Jin', 'Kim, Eun Young', 'Lee, Su Mi', 'Son, Young Ki', 'Nam, Hee-Joo', 'Kim, Ki-Ho', 'Lee, Soo-Keol', 'Park, Da-Eun', 'Kang, Hye-Ryun', 'Park, Heung Woo', 'Lee, Hyun Seung', 'Chang, Yoon-Seok', 'Park, Jung-Won', 'Cho, Sang-Heon', 'Min, Kyung-up', 'Song, Woo-Jung', 'Lim, Hyunwook', 'Seo, Sungchul', 'Choung, Ji Tae', 'Yoo, Young', 'Park, Jun-Sik', 'Kim, Byung Kwan', 'Won, Ha Kyeong', 'Kang, Hye-Ryun', 'Kim, Byung-Keun', 'Moon, Sung Do', 'Kim, Ju-Young', 'Lee, So-Hee', 'Song, Woo-Jung', 'Park, Heung Woo', 'Kang, Min-Koo', 'Kim, Sun-Sin', 'Cho, Sang-Heon', 'Min, Kyung-up', 'Chang, Yoon-Seok', 'Sohn, Kyoung Hee', 'Kim, Kyung-Mook', 'Kim, Ki-Woong', 'Jang, Hak Chul', 'Nam, Young-Hee', 'Jeon, Dong Sub', 'Nam, Hee-Joo', 'Noh, Yeo Myeong', 'Kim, Sang Hee Kim', 'Park, Ye Suel', 'Lee, Soo-Keol', 'Leung, Ting Fan', 'Tang, Man Fung', 'Sy, Hing Yee', 'Chan, Wa Cheong', 'Tam, Wilson Wai San', 'Chung, Seung Kyu', 'Kim, Sujin', 'Hong, Sang Duk', 'Kim, Hyo Yeol Kim Hyo Yeol', 'Dhong, Hun-Jong', 'Jeong, Jong in', 'Nam, Young-Hee', 'Jeon, Dong Sub', 'Lee, Soo-Keol', 'Lee, Ji Won', 'Kang, Mingyu', 'Kim, Soon-Hee', 'Bae, Boram', 'Kim, Sujeong', 'Kang, Hye-Ryun', 'Chang, Yoon-Seok', 'Song, Woo-Jung', 'Park, Da-Eun', 'Lee, Hyun Seung', 'Park, Heung Woo', 'Park, Han-Ki', 'Park, Jung-Won', 'Nam, Young-Hee', 'Jeon, Dong Sub', 'Nam, Hee-Joo', 'Noh, Yeo Myeong', 'Kim, Sang Hee Kim', 'Park, Ye Suel', 'Lee, Soo-Keol', 'Hou, Yung-I', 'Wang, Jiu-Yao', 'Kim, Ja Hyeong', 'Hee, Seol Jae', 'Ha, Eun-Hee', 'Park, Hyesook', 'Ha, Mina', 'Hong, Yun-Chul', 'Kim, Yangho', 'Chang, Namsoo', 'Soma, Yuta', 'Watanabe, So', 'Pawankar, Ruby', 'Suzaki, Harumi', 'Kobayashi, Hitome', 'Nam, Young-Hee', 'Park, Chansun', 'Lee, Soo-Keol', 'Lee, Jongrok', 'Roh, Jooyoung', 'Ryu, Haryeong', 'Kim, Cheol-Woo', 'Cho, Jae Hwa', 'Eom, Mi Ra', 'Kang, Ji Young', 'Lee, Hye Gyeung', 'Choi, Hae Young', 'Lee, Hye Jin', 'Woo, Ju Yun', 'Byun, Ji Yeon', 'Choi, You Won', 'Kim, Ja Hyeong', 'Ha, Eun-Hee', 'Park, Hyesook', 'Ha, Mina', 'Hong, Yun-Chul', 'Kim, Yangho', 'Chang, Namsoo', 'Kwon, Jae-Woo', 'Chang, Hun Soo', 'Heo, Jeong-Seok', 'Lee, Jong-Uk', 'Park, Jong-Sook', 'Kim, Eusom', 'Kim, Soo Hyun', 'Park, Choon-Sik', 'Choi, Hae Young', 'Byun, Ji Yeon', 'Woo, Ju Yun', 'Choi, You Won', 'Jin, Hyun-Ju', 'Son, Jin-Hwa', 'Kim, Jeong-Min', 'Kim, Gun-Wook', 'Mun, Je-Ho', 'Song, Margaret', 'Ko, Hyun-Chang', 'Kim, Moon-Bum', 'Kim, Hoon-Soo', 'Kim, Byung Soo', 'Van Nunen, Sheryl', 'Van Nguyen, Dinh', 'Elias, Anthony', 'Lauer, Susannah Olivia', 'Lee, Seung-Chul', 'Lee, Ho-June', 'Bae, Jung Min', 'Ono, Emi', 'Dong, Sung-Hwa', 'Koh, Tae Kyung', 'Byun, Young Seok', 'Kim, Sung Wan', 'Jo, Joong-Saeng', 'Kwon, Chul', 'Lee, Kun Hee', 'Liu, Li-Fan', 'Lee, Sunghee', 'Chen, Wei-Leng', 'Wang, Jiu-Yao', 'Bae, Youin', 'Park, Gyeong-Hun', 'Kim, Suk Yeon', 'Lee, Hyun Seung', 'Song, Woo-Jung', 'Kang, Mingyu', 'Park, Han-Ki', 'Park, Da-Eun', 'Kang, Hye-Ryun', 'Park, Heung Woo', 'Chang, Yoon-Seok', 'Kim, Hye-Young', 'Min, Kyung-up', 'Cho, Sang-Heon', 'Lee, Ji-Won', 'Bae, Boram', 'Park, Jung-Won', 'Suzuki, Yasuhiro', 'Bulut, Ismet', 'Ozseker, Zeynep Ferhan', 'Ismail, Intan Hakimah', 'Boyle, Robert', 'Licciardi, Paul', 'Oppedisano, Frances', 'Robins-Browne, Roy', 'Tang, Mimi', 'Lee, Ji Won', 'Lee, Hyun Seung', 'Kang, Mingyu', 'Park, Da-Eun', 'Park, Han-Ki', 'Kim, Soon-Hee', 'Song, Woo-Jung', 'Kang, Hye-Ryun', 'Park, Heung Woo', 'Chang, Yoon-Seok', 'Park, Chang-Han', 'Chang, Suk-Il', 'Song, Sook-Hee', 'Min, Kyung-up', 'Cho, Sang-Heon', 'Bae, Boram', 'Shieh, Grace', 'Kim, Min Jung', 'Hong, Jung Yeon', 'Yoon, Seo Hee', 'Shim, Doo Hee', 'Sol, In Suk', 'Kim, Yoon Hee', 'Kim, Mi Na', 'Lee, Kyung Eun', 'Kim, Kyung Won', 'Sohn, Myung Hyun', 'Kim, Kyu-Earn', 'Lee, Jae Myun', 'Chng, Hiok Hee', 'Kim, Dong Chan', 'Yang, Song-I', 'Lee, Hae Ran', 'Seo, An Deok', 'Lee, So Yeon', 'Artesani, Maria Cristina', 'Francalanci, Paola', 'Dahdah, Lamia', 'Schreiner, Thomas', 'Fiocchi, Alessandro', 'Chakraborty, Kaushik', 'Won, Ha Kyeong', 'Kim, Ju-Young', 'Jo, Eun-Jung', 'Sohn, Kyoung Hee', 'Kim, Kyung-Mook', 'Park, Heung Woo', 'Chang, Yoon-Seok', 'Cho, Sang-Heon', 'Song, Woo-Jung', 'Kim, Byung-Keun', 'Yonekura, Syuji', 'Okamoto, Yoshitaka', 'Hur, Gyu Young', 'Ye, Young Min', 'Kim, Joo-Hee', 'Jung, Ki-Suck', 'Kim, Junga', 'Shim, Jae Jeong', 'Park, Hae-Sim', 'Sekimoto, Kazuhiro', 'Sugai, Kazuko', 'Tsuchimoto, Keiji', 'Uehara, Hiromi', 'Ikeda, Masanori', 'Chung, Euncho', 'Park, Kang Seo', 'Choi, Yean Jung', 'Park, Jeewon', 'Hong, Soo-Jong', 'Lee, So Yeon', 'Jacquet, Alain', 'Buaklin, Arun', 'Malainual, Nat', 'Roopashree, S.', 'Kim, Kyu Rang', 'Kim, Mijin', 'Cho, Changbum', 'Kim, Baek-Jo', 'Oh, Jae-Won', 'Han, Mae Ja', 'Cho, Hyun-Ju', 'Shin, Youn Ho', 'Lee, Eun', 'Kim, Young-Ho', 'Lee, Darae', 'Kang, Mi-Jin', 'Yang, Song-I', 'Ahn, Kangmo', 'Kim, Kyung Won', 'Kim, Yoon Hee', 'Won, Hye-Sung', 'Kim, Soo Hyun', 'Choi, Suk-Joo', 'Kim, Young Han', 'Jun, Jong Kwan', 'Kim, Eun-Jin', 'Lee, Jeom Gyu', 'Lee, So-Yeon', 'Hong, Soo-Jong', 'Suh, Dongin', 'Amagai, Yosuke', 'Tanaka, Akane', 'Matsuda, Hiroshi', 'Mösges, Ralph', 'Dieterich, Pauline', 'Astvatsatourov, Anatoli', 'Hüser, Christoph', 'Singh, Jaswinder', 'Shah-Hosseini, Kija', 'Allekotte, Silke', 'Compalati, Enrico', 'Sohn, Kyoung Hee', 'Song, Woo-Jung', 'Kim, Byung-Keun', 'Kim, Ju-Young', 'Yang, Min Suk', 'Lee, So-Hee', 'Kim, Sae-Hoon', 'Kang, Hye-Ryun', 'Park, Heung Woo', 'Kim, Sun-Sin', 'Min, Kyung-up', 'Cho, Sang-Heon', 'Chang, Yoon-Seok', 'Chang, Woo-Sung', 'Do, Ji-Hye', 'Kim, Yeon-Seop', 'Yoon, Dankyu', 'Lim, Hye-Sun', 'Lee, Jeom-Kyu', 'Kim, Eun-Jin', 'Thong, Bernard', 'Cheng, Yew Kuang', 'Hou, Jinfeng', 'Leong, Khai Pang', 'Tan, Justina', 'Chia, Faith', 'Chan, Grace', 'Tan, Sze-Chin', 'Tan, Teck Choon', 'Tang, Chwee Ying', 'Chng, Hiok Hee', 'Park, Chan-Sun', 'Kim, Mi Yeoung', 'Kim, Eun-Young', 'Shin, Jae-Gook', 'Choi, Jae-Hyeog', 'Park, Saegwang', 'Kim, Yeonye', 'Lim, Kyung-Hwan', 'Jung, Jae Woo', 'Kang, Mingyu', 'Kim, Ju-Young', 'Kim, Ju-Young', 'Kim, Hyun Jeong', 'Woo, Yeon-Ju', 'Jung, Soo-Youn', 'Kang, Hye-Ryun', 'Kang, Hye-Ryun', 'Porée, Thierry', 'Boukhettala, Nabile', 'Furon, Emeline', 'Bullimore, Alan David', 'Heath, Matthew', 'Hewings, Simon', 'Skinner, Murray', 'Kurowski, Marcin', 'Krysztofiak, Hubert', 'Wardzynska, Aleksandra', 'Jarzebska, Marzanna', 'Jurczyk, Janusz', 'Kowalski, Marek L.', 'Kim, So Ri', 'Lee, Yong Chul', 'Kim, Dong Im', 'Rhee, Yang Keun', 'Lee, Heung Bum', 'Park, Seoung Ju', 'Choe, Yeong Hun Choe', 'Park, Seung Yong', 'Kim, Joo-Hee', 'Park, Sunghoon', 'Hwang, Young Il', 'Jang, Seung Hun', 'Jung, Ki-Suck', 'Min, Jiang', 'Guang-Min, Nong', 'Nag, Nalin', 'Indawati, Wahyuni', 'Bullimore, Alan David', 'Heath, Matthew', 'Skinner, Murray', 'Seo, Seong Jun', 'Oh, Won Jong', 'Bullimore, Alan David', 'Skinner, Murray', 'Heath, Matthew', 'Bell, Andrew', 'Hasanzadeh, Hournaz', 'Sadeghzade, Salman', 'Rezaei, Nima', 'Zarebidoki, Alireza', 'Cho, Kyu-Sup', 'Oh, Moo-Young', 'Kim, Sung-Woo', 'Koizumi, Munemitsu', 'Kuzume, Kazuyo', 'Park, Kui Young', 'Oh, Won Jong', 'Babaie, Delara', 'Nabavi, Mohammad', 'Zandieh, Fariborz', 'Moini, Mehrdad Amir', 'Chavoshzadeh, Zahra', 'Seifi, Hamideh', 'Sahragard, Mitra', 'Mesdaghi, Mehrnaz', 'Bemanian, Mohammad Hassan', 'Choi, Sun Young', 'No, Yeon a', 'Kiedik, Dorota', 'Muszynska, Agnieszka', 'Pirogowicz, Iwona', 'Fal, Andrzej M.', 'Motomura, Chikako', 'Wakatsuki, Masatoshi', 'Akamine, Yuko', 'Iwata, Mihoko', 'Matsuzaki, Hiroshi', 'Taba, Naohiko', 'Murakami, Yoko', 'Odajima, Hiroshi', 'Ghrahani, Reni', 'Takaoka, Yuri', 'Lee, Jong-Uk', 'Heo, Jeong-Seok', 'Bae, Da-Jeong', 'Song, Hyun Ji', 'Park, Choon-Sik', 'Park, Jong-Sook', 'Cho, Jae Hoon', 'Choi, Ji Ho', 'Febriana, Fiska', 'Ghrahani, Reni', 'Sapartini, Gartika', 'Setiabudiawan, Budi', 'Nam, Young-Hee', 'Kim, Mi Yeoung', 'Choi, Gil-Soon', 'Park, Chan-Sun', 'Huang, Chiung-Hui', 'Soh, Jian Yi', 'Shek, Lynette', 'Shek, Lynette', 'Delsing, Dianne J.', 'Lee, Bee Wah', 'Lee, Bee Wah', 'Goh, Si Hui', 'Chiang, Wen Chin', 'Loh, Wenyin', 'Yang, Hea-Kyoung', 'Lee, Ji Young', 'Kim, Minji', 'Ahn, Kangmo', 'Kim, Jihyun', 'Kim, Young-Min', 'Kim, Hye-Young', 'Park, Yong Mean', 'Kim, Woo Kyung', 'Lee, So-Yeon', 'Jeong, Jongin', 'Hong, Sang Duk', 'Chung, Seung Kyu', 'Dhong, Hun-Jong', 'Kim, Hyo Yeol', 'Kim, Sujin', 'Bak, Hana', 'Son, Hye-Rim', 'Lee, Si-Eun', 'Kim, Kwang-Jin', 'Lim, Young-Wook', 'Kim, Ho-Hyun', 'Lee, Yong-Won', 'Han, Man Yong', 'Jung, Young-Ho', 'Jee, Hye Mi', 'Lee, Seung Jin', 'Lee, Kyung Suk', 'Kim, Mi-Ae', 'Lee, Jaechun', 'Lee, Eunkyoung', 'Golez, Jasmina', 'Bae, Da-Jeong', 'Min, Chang-Gi', 'Lee, Jong-Uk', 'Park, Jong-Sook', 'Chang, Hun Soo', 'Park, Choon-Sik', 'Jang, An-Soo', 'Kim, Ha-Jung', 'Kim, Young-Joon', 'Jung, Bok Kyoung', 'Lee, Seung-Hwa', 'Kang, Mi-Jin', 'Jeong, Sekyoo', 'Lee, Eun', 'Cho, Hyun-Ju', 'Kim, Young-Ho', 'Yang, Song-I', 'Kim, Seo Hee', 'Hong, Soo-Jong', 'Halwani, Rabih', 'Al Muhsen, Saleh', 'Sultana, Asma', 'Al-Faraj, Achraf', 'Kanana, Rosan', 'Afzal, Sibtain', 'Al Kufaidi, Roaa', 'Kim, Hee-Kyoo', 'Oak, Chul-Ho', 'Choi, Gil-Soon', 'Moon, Ye-Jin', 'Park, Eun-Kee', 'Abrari, Mina', 'Amirzargar, Ali Akbar', 'Zarebidoki, Alireza', 'Ha, Mina', 'Hong, Soo-Jong', 'Seo, Ju-Hee', 'Kang, Mingyu', 'Cho, Byung-Ha', 'Park, Han-Ki', 'Park, Han-Ki', 'Kim, Kyung-Mook', 'Park, Chang-Han', 'Park, Heung Woo', 'Park, Heung Woo', 'Chang, Yoon-Seok', 'Chang, Yoon-Seok', 'Chang, Yoon-Seok', 'Song, Sook-Hee', 'Kim, Mi-Kyeong', 'Kim, Mi-Kyeong', 'Cho, Sang-Heon', 'Chang, Suk-Il', 'Min, Kyung-up', 'Min, Kyung-up', 'Morice, Alyn', 'Choi, Jungi', 'Han, Yusok', 'Park, Jin-Sung', 'Kwon, Eunmi', 'Kim, Chang-Keun', 'Sapartini, Gartika', 'Kim, Ji-Na', 'Shin, Seungwoo', 'Chang, Hun Soo', 'Shim, Eun-Young', 'Jun, Ji Ah', 'Lee, Hyeonju', 'Park, Jong-Sook', 'Park, Choon-Sik', 'Sepiashvili, Revaz', 'Khachapuridze, Darejan', 'Gamkrelidze, Sofio', 'Chikhladze, Manana', 'Lee, Seung-Eun', 'Kim, Yun-Seong', 'Jeon, Doo-Soo', 'Cho, Woo-Hyun', 'Yeo, Hye-Ju', 'Yoon, Seong-Hoon', 'Kim, Seung-Hyun', 'Lee, Taehyeong', 'Song, Hyun Ji', 'Park, Choon-Sik', 'Jun, Ji Ah', 'Park, Jong-Sook', 'Yoon, Dankyu', 'Kim, Yeon-Seop', 'Chang, Woo-Sung', 'Kang, Mi-Jin', 'Hong, Soo-Jong', 'Lee, Jeom-Kyu', 'Kim, Eun-Jin', 'Park, Minkee', 'Lee, Nanju Alice', 'Rost, Johanna', 'Muralidharan, Sridevi', 'Campbell, Dianne', 'Mehr, Sam', 'Lee, Seung-Hwa', 'Yoon, Seon-Joo', 'Kim, Ha-Jung', 'Lee, Eun', 'Yang, Song-I', 'Jung, Young-Ho', 'Yu, Ho-Sung', 'Kim, Hee-Suk', 'Park, Yeon Hee', 'Lee, So-Yeon', 'Park, Jun-Sung', 'Jun, Hyun Ok', 'Won, Ha Kyeong', 'Kang, Min-Koo', 'Moon, Sung Do', 'Kim, Byung-Keun', 'Kim, Ju-Young', 'Cho, Sang-Heon', 'Kang, Hye-Ryun', 'Shim, Ji-Su', 'Chung, Soo Jie', 'Choi, Jaehee', 'Ahn, Kangmo', 'Kim, Kwanghoon', 'Kim, Jihyun', 'Lee, Jiyoung', 'Park, Bo Bae', 'Nho, In Young', 'Park, Chang-Han', 'Kim, Jang Min', 'Chang, Suk-Il', 'Kim, Sun Kyung', 'Yang, Hyung Chae', 'Nam, Kwang Il', 'Lee, Jeongmin', 'Lee, Sooyoung', 'Jeong, Kyunguk', 'Jeon, Se-Ah', 'Fujiwara, Midori', 'Shindo, Shoko', 'Murota, Hiroyuki', 'Tahara, Mayuko', 'Takahashi, Aya', 'Katayama, Ichiro', 'Jung, Jae Woo', 'Song, Hyun Ji', 'Lee, Taehyeong', 'Jang, An-Soo', 'Park, Jong-Sook', 'Chang, Hun Soo', 'Park, Choon-Sik', 'Choi, Byoung Whui', 'Kim, Min-Hye', 'Bae, Da-Jeong', 'Song, Hyun Ji', 'Lee, Taehyeong', 'Jun, Ji Ah', 'Park, Jong-Sook', 'Jang, An-Soo', 'Chang, Hun Soo', 'Cho, Young Joo', 'Park, Choon-Sik', 'Mun, Sue Jean', 'Kuroda, Etsushi', 'Ozasa, Koji', 'Ishii, Ken', 'Kim, Sunmi', 'Park, Gyeong-Hun', 'Song, Hyun Ji', 'Lee, Taehyeong', 'Jun, Ji Ah', 'Chang, Hun Soo', 'Park, Jong-Sook', 'Park, Choon-Sik', 'Kim, Mi-Ae', 'Shin, Seungwoo', 'Park, Jong-Sook', 'Chang, Hun Soo', 'Cho, You Sook', 'Park, Hae-Sim', 'Park, Choon-Sik', 'Min, Zhang', 'Yoon, Seo Hee', 'Sol, In Suk', 'a Park, Young', 'Kim, Yoon Hee', 'Kim, Min Jung', 'Kim, Kyung Won', 'Sohn, Myung Hyun', 'Kim, Kyu-Earn', 'Shiquan, Wu', 'Lee, Yongwon', 'Bak, Hana', 'Ching, Maricar Wisco', 'Ramos, John Donnie', 'Jeong, Kyunguk', 'Lee, Sooyoung', 'Ahn, Kangmo', 'Sohn, Myung Hyun', 'Kim, Kyung Won', 'Lee, So-Yeon', 'Song, Tae Won', 'Jeon, Youhoon', 'Kim, Jihyun', 'Min, Taek Ki', 'Kim, Kyu-Earn', 'Pyun, Bok-Yang', 'Yang, Hyeon-Jong', 'Lee, Hae Ran', 'Ahn, Youngmin', 'Kwon, Ji-Won', 'Lim, Dae Hyun', 'Kim, Jeong Hee', 'Suh, Dongin', 'Ki, Hyung Young', 'Jeong, Kyunguk', 'Park, Byeong Sub', 'Lee, Sooyoung', 'Jeon, Se-Ah', 'Park, Kyu Jung', 'Yang, Song-I', 'Lee, Eun', 'Cho, Hyun-Ju', 'Kim, Young-Ho', 'Kang, Mi-Jin', 'Choi, Yean Jung', 'Choi, Kil Yong', 'Shin, Youn Ho', 'Ahn, Kangmo', 'Kim, Kyung Won', 'Kim, Byoung-Ju', 'Lee, So-Yeon', 'K, Eun-Jin', 'Dario, Roccatello', 'Liao, Jing', 'Feng, Yong', 'Shang, Yunxiao', 'Lee, Yongwon', 'Bak, Hana', 'Kim, Hyung Young', 'Kim, Byoung-Ju', 'Kwon, Ji-Won', 'Seo, Ju-Hee', 'Lee, Eun', 'Lee, So-Yeon', 'Yang, Song-I', 'Jung, Young-Ho', 'Kim, Hyo-Bin', 'Kwon, Ho-Jang', 'Park, Hee Ju', 'Min, Zhang', 'Guang-Min, Nong', 'Min, Jiang', 'Hur, Gyu Young', 'Sim, Eun Jung', 'Yoon, Sora', 'Choi, Juwhan', 'Kim, Junga', 'Sim, Jae Keom', 'Oh, Jee Youn', 'Jeong, Kyunguk', 'Park, Byeong Sub', 'Lee, Jeong-Min', 'Lee, Sooyoung', 'Cheon, Eunjae', 'Na, Youngjoo', 'Park, Kyu Jung', 'Lee, Eunjoo', 'Yang, William', 'Kelly, Suzanne', 'Perrins, Rob', 'Yang, Jimmy', 'Yang, William', 'Kelly, Suzanne', 'Perrins, Rob', 'Karsh, Jacob', 'Yang, Jimmy', 'Badellino, Hector', 'Teijeiro, Alvaro', 'Cuello, Mabel', 'Pereira, Marilyn Urrutia', 'Egues, Gustavo', 'Aktas, Ayse', 'Chun, Jin-Kyong', 'Mujuru, Hilda Angela', 'Sibanda, Elopy N.', 'Popescu, Andreea Ioana', 'Greblescu, Raluca', 'Rahman, Suheyla', 'Aktas, Ayse', 'Tataurshchikova, Nataly', 'Dissanayake, Eishika', 'Inoue, Yuzaburo', 'Shimojo, Naoki', 'Nakano, Taiji', 'Tanjung, Conny', 'Jensen-Jarolim, Erika', 'Fazekas, Judit', 'Singer, Josef', 'Lukschal, Anna', 'Horvat, Reinhard', 'Achatz-Straussberger, Gertrude', 'Achatz, Gernot', 'Fujita, Yuji', 'Ikegami, Shuji', 'Nakamura, Yoshitaka', 'Inoue, Yuzaburo', 'Shimojo, Naoki', 'Kohno, Yoichi', 'Suzuki, Shuichi', 'Ozawa, Naoko', 'Kubota, Takayuki', 'Nonaka, Ken', 'Ohara, Osamu', 'Masuda, Kentaro', 'Rhee, Chin Kook', 'Lee, Sook Young', 'Lee, Hwa Young', 'Lee, Hea Yon', 'Kang, Ji Young', 'Kim, Sei Won', 'Kwon, Soon Seog', 'Kim, Young Kyoon', 'Kim, Gun-Woo', 'Kim, Ju-Young', 'Cho, Sang-Heon', 'Cho, Sang-Heon', 'Kang, Hye-Ryun', 'Kang, Hye-Ryun', 'Kim, Hyo-Soo', 'Han, Jung Gyu', 'Lee, Jin', 'Lee, Ji Young', 'Go, Ji Young', 'Park, So Jung', 'Kim-Chang, Julie', 'Love, Cassandra', 'Lugar, Patricia', 'Citraresmi, Endah', 'Kaswandani, Nastiti', 'Utami, Cynthia', 'Said, Mardjanis', 'Jung, Young-Ho', 'Yang, Song-I', 'Kim, Byoung-Ju', 'Kwon, Ji-Won', 'Kim, Hwan-Cheol', 'Leem, Jong-Han', 'Seo, Ju-Hee', 'Kim, Hyung Young', 'Lee, So-Yeon', 'Kwon, Ho-Jang', 'Kim, Hyo-Bin', 'Cho, Hyun-Ju', 'Yamazaki, Susumu', 'Nakano, Nobuhiro', 'Honjoh, Asuka', 'Inage, Eisuke', 'Baba, Yosuke', 'Ohtsuka, Yoshikazu', 'Shimizu, Toshiaki', 'M., Ishaq', 'Khan, Sameera M. I.', 'Khan, Imran', 'Khan, Sabeen', 'Loo, Evelyn Xiu Ling', 'Goh, Anne', 'Teoh, Oon Hoe', 'Chan, Yiong Huak', 'Saw, Seang Mei', 'Kwek, Kenneth', 'Gluckman, Peter D', 'Godfrey, Keith M', 'Van Bever, Hugo', 'Chong, Yap Seng', 'Lee, Bee Wah', 'Shek, Lynette', 'Lee, Alison Joanne', 'Rossi, Daniela', 'Nemeth, Agnes', 'Sehlinger, Torsten', 'Bergmann, Karl-Christian', 'Goergen, Frank', 'Ehlayel, Mohammad S.', 'Bener, Abdul Bari', 'Chu, Hieu Chi', 'Do, Nga Thi Quynh', 'Van Nguyen, Dinh', 'Nguyen, Ha Thi Thu', 'Le, Huong Thi Minh', 'Van Nunen, Sheryl', 'Vidal, Christopher', 'Fernando, Suran', 'Psarros, Fotis', 'Syrigou, Ekaterini', 'Politi, Ekaterini', 'Chrysoulakis, Spyridon', 'Vourdas, Dimitrios', 'Petalas, Konstantinos', 'Saha, Mouli', 'Bhattacharya, Kashinath', 'Jain, Subir', 'Song, Xiaolian', 'Lin, Haiyan', 'Nishikawa, Kyohei', 'Shimada, Takashi', 'Yasueda, Hiroshi', 'Enomoto, Tadao', 'Aizawa, Daisuke', 'Kobayashi, Takayoshi', 'R., Chellaa', 'Jain, Subir', 'Jain, Subir', 'Yudina, Marina', 'M., Ishaq', 'Khan, Sameera M. I.', 'Khan, Imran', 'Khan, Sabeen', 'Saito, Mayako', 'Sari, Nurul Iman Nilam', 'Kim, Jae Young', 'Song, Jaechul', 'Kim, Inah', 'Lee, Kyeong Joon', 'Park, Soo Jin', 'Roh, Soo Yong', 'Billamay, Somxay', 'Udin, Muchammad Fahrul', 'Han, Mae Ja', 'Oh, Jae-Won', 'Kim, Kyu Rang', 'Kim, Baek-Jo', 'Mazza, Jorge A.', 'Ko, Jason Kangeun', 'Huang, David J. T.', 'Furuya, Kanae', 'Kainuma, Keigo', 'Ito, Takahiro', 'Nagao, Mizuho', 'Fujisawa, Takao', 'Hirayama, Junya', 'Kuwahara, Yu', 'Qualizza, Rosanna', 'Incorvaia, Cristoforo', 'Maraschini, Anna', 'Hasnain, Syed Mohammed', 'Al-Frayh, Abdulrahman', 'Hartog, Anita', 'Bastiaans, Jacqueline', 'Loonstra, Reinilde', 'Rutten, Lieke', 'Harthoorn, Lucien', 'Van Bergenhenegouwen, Jeroen', 'Garssen, Johan', 'Yoo, Kwang-Ha', 'Cho, Sang-Heon', 'Ghoshal, AG', 'Muttalif, Abdul Razak Bin Abdul', 'Lin, Horng- Chyuan', 'Thanaviratananich, Sanguansak', 'Bagga, Shalini', 'Faruqi, Rab', 'Baidya, Santwona', 'Taylor, Colman', 'Wang, De Yun', 'Ahn, Hae-Ryun', 'Hong, Soon-Kwan', 'Kim, Jong-Woong', 'Nam, Gui-Hyun', 'Kim, Mee-Ja', 'Park, Jae-Kyoung', 'Yi, Myung-Hee', 'Jeong, Kyoung Yong', 'Kim, Ju-Yeong', 'Yong, Tai-Soon', 'Kim, Bum Joon', 'Joo, Hs', 'Lim, Kj', 'Lee, Jae-Hyun', 'Park, Jung-Won', 'Yoon, Kh', 'Choi, DS', 'Joo, Hanseung', 'Kim, Bum Joon', 'Lim, Kj', 'Kim, MJ', 'Choi, DS', 'Yoon, Kh', 'Kim, Bum Joon', 'Joo, Hanseung', 'Jung, Woo Sang', 'Lim, Kj', 'Choi, DS', 'Lee, Ji-Hoon', 'Kwon, Soon-Chan', 'Lee, Soo-Jin', 'Roh, Soo Yong', 'Kim, Hogil', 'Lee, Kyeong Joon', 'Van De Loo, Aurora', 'Fernstrand, Amanda', 'Garssen, Johan', 'Verster, Joris', 'Van De Loo, Aurora', 'Garssen, Johan', 'Verster, Joris', 'Golez, Jasmina', 'Ozasa, Koji', 'Kuroda, Etsushi', 'Ishii, Ken', 'Imran, Muhammad', 'Gierer, Selina', 'Martinez, John', 'Wong, Lydia', 'Lee, Bee Wah', 'Yap, Gaik Chin', 'Llanora, Genevieve', 'Thong, Bernard', 'Shek, Lynette', 'Ehlayel, Mohammad S.', 'Soliman, Ashraf', 'Martins, Pedro', 'Marques, João', 'Gomes-Belo, Joana', 'Palmeiro, Teresa', 'Caires, Iolanda', 'Belo, Joana', 'Botelho, Maria Amália', 'Leiria-Pinto, Paula', 'Neuparth, Nuno', 'Suratannon, Narissara', 'Mekaroonkamol, Jaichat', 'Ngamphaiboon, Jarungchit', 'Lertchanaruengrith, Piyawadee', 'Chatchatee, Pantipa', 'Kardar, Gholamali', 'Majd, Ahmad', 'Shahali, Youcef', 'Ghahremaninejad, Farrokh', 'Pourpak, Zahra', 'Mousavi, Fateme', 'Sadeghi-Shabestari, Mahnaz', 'Van Bilsen, K.', 'Manusama, O.', 'Dik, W.a.', 'Van Der Burg, M.', 'Van Der Velden, V. H. J.', 'Dalm, V.a.S. H.', 'Van Hagen, P. M.', 'Liu, Yongping', 'Jeong, Yi Yeong', 'Kim, Ji Hye', 'Yoon, Moon Gyeong', 'Ye, Young Min', 'Shin, Yoo Seob', 'Ban, Ga Young', 'Park, Hae-Sim', 'Jung, Hye Min', 'Roh, Soo Yong', 'Song, Jaechul', 'Lee, Ji-Hoon', 'Kim, Hogil', 'Kim, Jae Young', 'Lee, Kyeong Joon', 'Wong, Lydia', 'Rajakulendran, Mohana', 'Santhanam, Haripriya', 'Shek, Lynette', 'Lim, Tow Keang', 'Kim, Hogil', 'Lee, Soo-Jin', 'Lee, Ji-Hoon', 'Roh, Soo Yong', 'Kwon, Soon-Chan', 'Wistiani, Ani', 'H, Galuh', 'Kardar, Gholam Ali', 'Sharifshoushtari, Maryam', 'Majd, Ahmad', 'Nejadsattari, Taher', 'Pourpak, Zahra', 'Moin, Mostafa', 'Kim, Ji Hye', 'Seo, Daehong', 'Ye, Young Min', 'Park, Hae-Sim', 'Park, Jung-Won', 'Lee, Jae-Hyun', 'Shin, Yoo Seob', 'Kowalski, Marek L.', 'Wardzynska, Aleksandra', 'Kurowski, Marcin', 'Pawelczyk, Malgorzata/Ewa', 'Wysokinski, Adam', 'Kloszewska, Iwona', 'Grzegorczyk, Janina', 'Piotrowski, Wojciech', 'Makowska, Joanna', 'Kwon, Soon-Chan', 'Song, Jaechul', 'Kim, Yong-Kyu', 'Bostanci, Ilknur', 'Emeksiz, Zeynep Sengul', 'Ertugrul, Aysegul', 'Ozmen, Serap', 'Sahin, Soner', 'Kim, Sang-Ha', 'Lee, Myoung Kyu', 'Lee, Won Yeon', 'Yong, Suk Joong', 'Lee, Seok Jeong', 'Jung, Ye-Ryung', 'Kim, Myung Shin', 'Park, Jong-Sook', 'Jang, An-Soo', 'Park, Choon-Sik', 'Wulandari, Diah Asri', 'Kartasasmita, Cissy', 'Yani, Finny Fitry', 'Machmud, Rizanda', 'Lestari, Dhina Lydia', 'Rusdi, Rusdi', 'Yurmalina, Yurmalina', 'Darwin, Eryati', 'Bostanci, Ilknur', 'Karacan, Gulin', 'Ercan, Nazli', 'Colak, Asuman', 'Alisik, Murat', 'Basarir, Gulay', 'Erel, Ozcan', 'Bostanci, Ilknur', 'Keskin, Yasemin', 'Lopata, Andreas/Ludwig', 'Zenger, Kyall', 'Nugraha, Roni', 'Kamath, Sandip', 'Bielory, Leonard', 'Georgopoulos, Panos', 'Zhang, Yong', 'Mi, Wheat', 'Cai, Ting', 'Xian, MO', 'Li, Jing', 'Feng, Mulin']",World Allergy Organ J,,,True
f39671c6a9f5a19d6db58094f4a8f07f6e036085,PMC,The host immune response in respiratory virus infection: balancing virus clearance and immunopathology,http://dx.doi.org/10.1007/s00281-016-0558-0,PMC4896975,26965109,CC BY,"The respiratory tract is constantly exposed to the external environment, and therefore, must be equipped to respond to and eliminate pathogens. Viral clearance and resolution of infection requires a complex, multi-faceted response initiated by resident respiratory tract cells and innate immune cells and ultimately resolved by adaptive immune cells. Although an effective immune response to eliminate viral pathogens is essential, a prolonged or exaggerated response can damage the respiratory tract. Immune-mediated pulmonary damage is manifested clinically in a variety of ways depending on location and extent of injury. Thus, the antiviral immune response represents a balancing act between the elimination of virus and immune-mediated pulmonary injury. In this review, we highlight major components of the host response to acute viral infection and their role in contributing to mitigating respiratory damage. We also briefly describe common clinical manifestations of respiratory viral infection and morphological correlates. The continuing threat posed by pandemic influenza as well as the emergence of novel respiratory viruses also capable of producing severe acute lung injury such as SARS-CoV, MERS-CoV, and enterovirus D68, highlights the need for an understanding of the immune mechanisms that contribute to virus elimination and immune-mediated injury.",2016 Mar 10,"['Newton, Amy H.', 'Cardani, Amber', 'Braciale, Thomas J.']",Semin Immunopathol,,,True
d78837afeedbb3c9dfa91a675aa03d34ef5a4387,PMC,The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation,http://dx.doi.org/10.1007/s00281-016-0555-3,PMC4896990,26957481,CC BY,"Acute and chronic inflammatory responses in the lung are associated with the accumulation of large quantities of immune and structural cells undergoing apoptosis, which need to be engulfed by phagocytes in a process called ‘efferocytosis’. Apoptotic cell recognition and removal from the lung is mediated predominantly by airway macrophages, though immature dendritic cells and non-professional phagocytes, such as epithelial cells and mesenchymal cells, can also display this function. Efficient clearance of apoptotic cells from the airways is essential for successful resolution of inflammation and the return to lung homeostasis. Disruption of this process leads to secondary necrosis of accumulating apoptotic cells, release of necrotic cell debris and subsequent uncontrolled inflammatory activation of the innate immune system by the released ‘damage associated molecular patterns’ (DAMPS). To control the duration of the immune response and prevent autoimmune reactions, anti-inflammatory signalling cascades are initiated in the phagocyte upon apoptotic cell uptake, mediated by a range of receptors that recognise specific phospholipids or proteins externalised on, or secreted by, the apoptotic cell. However, prolonged activation of apoptotic cell recognition receptors, such as the family of receptor tyrosine kinases Tyro3, Axl and MerTK (TAM), may delay or prevent inflammatory responses to subsequent infections. In this review, we will discuss recent advances in our understanding of the mechanism controlling apoptotic cell recognition and removal from the lung in homeostasis and during inflammation, the contribution of defective efferocytosis to chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease, asthma and cystic fibrosis, and implications of the signals triggered by apoptotic cells in the susceptibility to pulmonary microbial infections.",2016 Mar 8,"['Grabiec, Aleksander M.', 'Hussell, Tracy']",Semin Immunopathol,,,True
1699f74dc5e3e5ee7417778d18f7f5a46fb7c879,PMC,Equine rhinitis B viruses in horse fecal samples from the Middle East,http://dx.doi.org/10.1186/s12985-016-0547-x,PMC4897857,27267372,CC BY,"BACKGROUND: Among all known picornaviruses, only two species, equine rhinitis A virus and equine rhinitis B virus (ERBV) are known to infect horses, causing respiratory infections. No reports have described the detection of ERBV in fecal samples of horses and no complete genome sequences of ERBV3 are available. METHODS: We performed a molecular epidemiology study to detect ERBVs in horses from Dubai and Hong Kong. Complete genome sequencing of the ERBVs as well as viral loads and genome, phylogenetic and evolutionary analysis were performed on the positive samples. RESULTS: ERBV was detected in four (13.8 %) of the 29 fecal samples in horses from Dubai, with viral loads 8.28 × 10(3) to 5.83 × 10(4) copies per ml, but none of the 47 fecal samples in horses from Hong Kong by RT-PCR. Complete genome sequencing and phylogenetic analysis showed that three of the four strains were ERBV3 and one was ERBV2. The major difference between the genomes of ERBV3 and those of ERBV1 and ERBV2 lied in the amino acid sequences of their VP1 proteins. The Ka/Ks ratios of all the coding regions in the ERBV3 genomes were all <0.1, suggesting that ERBV3 were stably evolving in horses. Using the uncorrelated lognormal distributed relaxed clock model on VP1 gene, the date of the most recent common ancestor (MRCA) of ERBV3 was estimated to be 1785 (HPDs, 1176 to 1937) and the MRCA dates of ERBV1 and ERBV2 were estimated to be 1848 (HPDs, 1466 to 1949) respectively. CONCLUSIONS: Both acid stable (ERBV3) and acid labile (ERBV2) ERBVs could be found in fecal samples of horses. Detection of ERBVs in fecal samples would have implications for their transmission and potential role in gastrointestinal diseases as well as fecal sampling as an alternative method of identifying infected horses.",2016 Jun 7,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Choi, Garnet K. Y.', 'Huang, Yi', 'Wernery, Renate', 'Joseph, Sunitha', 'Wong, Emily Y. M.', 'Elizabeth, Shyna K.', 'Patteril, Nissy Annie Georgy', 'Li, Tong', 'Wernery, Ulrich', 'Yuen, Kwok-Yung']",Virol J,,,True
9a679e9fdf3590b7f9204c3dc3ff6307c3d4642b,PMC,Global research trends of Middle East respiratory syndrome coronavirus: a bibliometric analysis,http://dx.doi.org/10.1186/s12879-016-1600-5,PMC4897912,27267256,CC BY,"BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is a virus that causes severe viral pneumonia in humans, known to have a high mortality rate and a similarity in clinical symptoms with severe acute respiratory syndrome coronavirus. It was first isolated in Kingdom of Saudi Arabia (KSA) in 2012 and after that, MERS-CoV exhibited outbreaks in several regions of the world. This study aimed to assess the characteristics of publications involving MERS-CoV at global level by using a bibliometric analysis. METHODS: Scopus database was searched on March 4, 2016 for MERS-CoV publications published between 2012 and 2015. It was performed on the same day in order to avoid the possible bias came from update on the database because the metrics are changing over time. All publication types were considered; however publications as errata were excluded. Analysis parameters include year of publication, publication type, patterns of international collaboration, research institutions, journals, impact factor, h-index, language, and times cited. RESULTS: A total of 883 MERS-CoV research publications were published across the world. The MERS-CoV-associated publications were originated from 92 countries/territories, indicating the international spread of MERS-CoV research. The USA was the largest contributor, with 319 articles published over 4 years, followed by KSA (113 articles). The total number of citations for these publications has already achieved 8,015, with an average of 9.01 citations per each publication. The h-index for MERS-CoV-associated publications was 48. The USA also have the highest h-index (32), followed by KSA (26) and UK (22). Netherland produced the greatest proportion of publications with international research collaboration (72.7 %) followed by the UK (71 %) and Germany (69.1 %) out of the total number of publications for each country. CONCLUSIONS: There is a rapid increase in research activities related to MERS-CoV from 2012 to 2015. This study demonstrates that the MERS-CoV related literature has grown to be more extensive and global over the past 4 years. The bulk of publications in the field of MERS-CoV research are published by high-income countries such as the USA. Furthermore, the USA, the UK and KSA may have higher quality of articles according to the value of h-index.",2016 Jun 7,"Zyoud, Sa’ed H.",BMC Infect Dis,,,True
8a58dd3509470bd8a8a25fa473991ca6681066d9,PMC,Development of monoclonal antibodies and serological assays including indirect ELISA and fluorescent microsphere immunoassays for diagnosis of porcine deltacoronavirus,http://dx.doi.org/10.1186/s12917-016-0716-6,PMC4898321,27277214,CC BY,"BACKGROUND: A novel porcine deltacoronavirus (PDCoV), also known as porcine coronavirus HKU15, was reported in China in 2012 and identified in the U.S. in early 2014. Since then, PDCoV has been identified in a number of U.S. states and linked with clinical disease including acute diarrhea and vomiting in the absence of other identifiable pathogens. Since PDCoV was just recently linked with clinical disease, few specific antibody-based reagents were available to assist in diagnosis of PDCoV and limited serological capabilities were available to detect an antibody response to this virus. Therefore, the overall objective of this project was to develop and validate selected diagnostic reagents and assays for PDCoV antigen and antibody detection. RESULTS: The nucleoprotein of PDCoV was expressed as a recombinant protein and purified for use as an antigen to immunize mice for polyclonal, hyperimmune sera and monoclonal antibody (mAb) production. The resulting mAbs were evaluated for use in fluorescent antibody staining methods to detect PDCoV infected cells following virus isolation attempts and for immunohistochemistry staining of intestinal tissues of infected pigs. The same antigen was used to develop serological tests to detect the antibody response to PDCoV in pigs following infection. Serum samples from swine herds with recent documentation of PDCoV infection and samples from expected naïve herds were used for initial assay optimization. The tests were optimized in a checkerboard fashion to reduce signal to noise ratios using samples of known status. Statistical analysis was performed to establish assay cutoff values and assess diagnostic sensitivities and specificities. At least 629 known negative serum samples and 311 known positive samples were evaluated for each assay. The enzyme linked immunosorbent assay (ELISA) showed diagnostic sensitivity (DSe) of 96.1 % and diagnostic specificity (DSp) of 96.2 %. The fluorescent microsphere immunoassay (FMIA) showed a DSe of 95.8 % and DSp of 98.1 %. Both ELISA and FMIA detected seroconversion of challenged pigs between 8–14 days post-infection (DPI). An indirect fluorescent antibody (IFA) test was also developed using cell culture adapted PDCoV for comparative purposes. CONCLUSION: These new, specific reagents and serological assays will allow for improved diagnosis of PDCoV. Since many aspects of PDCoV infection and transmission are still not fully understood, the reagents and assays developed in this project should provide valuable tools to help understand this disease and to aid in the control and surveillance of porcine deltacoronavirus outbreaks.",2016 Jun 8,"['Okda, Faten', 'Lawson, Steven', 'Liu, Xiaodong', 'Singrey, Aaron', 'Clement, Travis', 'Hain, Kyle', 'Nelson, Julie', 'Christopher-Hennings, Jane', 'Nelson, Eric A.']",BMC Vet Res,,,True
b4ced0e08f5b03e84a5addaaf3557b3cdc1ef277,PMC,Nucleotide composition of the Zika virus RNA genome and its codon usage,http://dx.doi.org/10.1186/s12985-016-0551-1,PMC4898363,27278486,CC BY,"BACKGROUND: RNA viruses have genomes with a distinct nucleotide composition and codon usage. We present the global characteristics of the RNA genome of Zika virus (ZIKV), an emerging pathogen within the Flavivirus genus. ZIKV was first isolated in 1947 in Uganda, caused a widespread epidemic in South and Central America and the Caribbean in 2015 and has recently been associated with microcephaly in newborns. METHODS: The nearly 11 kb positive-stranded RNA genome of ZIKV was analyzed for its nucleotide composition, also in the context of the folded RNA molecule. Nucleotide trends were investigated along the genome length by skew analyses and we analyzed the codons used for translation of the ZIKV proteins. RESULTS: ZIKV RNA has a biased nucleotide composition in being purine-rich and pyrimidine-poor. This preference for purines is a general characteristic of the mosquito-borne and tick-borne flaviviruses. The virus-specific nucleotide bias is further enriched in the unpaired, single-stranded regions of the structured ZIKV RNA genome, thus further imposing this ZIKV-specific signature. The codons used for translation of the ZIKV proteins is also unusual, but we show that it is the underlying bias in nucleotide composition of the viral RNA that largely dictates these codon preferences. CONCLUSIONS: The ZIKV RNA genome has a biased nucleotide composition that dictates the codon usage of this flavivirus. We discuss the evolutionary scenarios and molecular mechanisms that may be responsible for these distinctive ZIKV RNA genome features.",2016 Jun 8,"['van Hemert, Formijn', 'Berkhout, Ben']",Virol J,,,True
d90382cb2b05e6761cea35d274213ee4f5c0cd02,PMC,Assessment of pathogenicity and tissue distribution of infectious bronchitis virus strains (Italy 02 genotype) isolated from moroccan broiler chickens,http://dx.doi.org/10.1186/s12917-016-0711-y,PMC4898447,27277076,CC BY,"BACKGROUND: Avian infectious bronchitis (IB) is one of the most important viral diseases of poultry, affecting chickens of all ages and causing major economic losses in poultry flocks. Mass vaccination is conducted in Morocco using a vaccine against Massachusetts, which is the most dominant serotype; however no information about the pathogenesis and tissue distribution of the Moroccan Italy 02 genotype was reported. 40 one-day-old specific pathogen free chickens were divided randomly into four groups. Group1, 2 and 3 were inoculated intra oculo-nasally with 103.5 EID50 of Italy02 viruses, and group 4 was kept as control. Chickens in each group were monitored for 14 days post-infection (pi). RESULTS: Chickens in all infected groups showed severe respiratory signs, which most of them have been reproduced on 2dpi, with varying times of appearance and disappearance. The infected birds appeared lethargic, reluctant to move, with specific respiratory clinical signs and macroscopic lesions. However no nephritis lesions or mortality were recorded in all groups. The specific histological lesions finding in all infected birds, exhibited tracheal lesions with mucosal thickening, hyperplasia of the surface epithelium, mononuclear inflammatory cell infiltrate of lamina propria. Primary and secondary bronchi, epithelial hyperplasia and mononuclear inflammatory cell infiltrate of the lamina propria were also observed. Tracheal lesions developed in all infected birds, confirm the ability of the three tested strains to induce respiratory disease. The results at 14 dpi also revealed that all strains were able to induce serological response. Virus re-isolation from infected organs and amplification of the viral RNA by real-time PCR proved the presence of the virus in lung and trachea of infected chicks. Neither re-isolation nor significant viral RNA detection were detected in the kidney. CONCLUSION: The results demonstrated that the three strains Italy02 genotype emerging in Moroccan poultry farms have a wide distribution for respiratory system, without kidney damage and without causing mortality.",2016 Jun 8,"['Khataby, Khadija', 'Kichou, Faouzi', 'Loutfi, Chafiqa', 'Ennaji, My Mustapha']",BMC Vet Res,,,True
1f4d59790ebb50fad78486e25156bcbb6b1edb40,PMC,Identify-Isolate-Inform: A Tool for Initial Detection and Management of Zika Virus Patients in the Emergency Department,http://dx.doi.org/10.5811/westjem.2016.3.30188,PMC4899052,27330653,CC BY,"First isolated in 1947 from a monkey in the Zika forest in Uganda, and from mosquitoes in the same forest the following year, Zika virus has gained international attention due to concerns for infection in pregnant women potentially causing fetal microcephaly. More than one million people have been infected since the appearance of the virus in Brazil in 2015. Approximately 80% of infected patients are asymptomatic. An association with microcephaly and other birth defects as well as Guillain-Barre Syndrome has led to a World Health Organization declaration of Zika virus as a Public Health Emergency of International Concern in February 2016. Zika virus is a vector-borne disease transmitted primarily by the Aedes aegypti mosquito. Male to female sexual transmission has been reported and there is potential for transmission via blood transfusions. After an incubation period of 2–7 days, symptomatic patients develop rapid onset fever, maculopapular rash, arthralgia, and conjunctivitis, often associated with headache and myalgias. Emergency department (ED) personnel must be prepared to address concerns from patients presenting with symptoms consistent with acute Zika virus infection, especially those who are pregnant or planning travel to Zika-endemic regions, as well as those women planning to become pregnant and their partners. The identify-isolate-inform (3I) tool, originally conceived for initial detection and management of Ebola virus disease patients in the ED, and later adjusted for measles and Middle East Respiratory Syndrome, can be adapted for real-time use for any emerging infectious disease. This paper reports a modification of the 3I tool for initial detection and management of patients under investigation for Zika virus. Following an assessment of epidemiologic risk, including travel to countries with mosquitoes that transmit Zika virus, patients are further investigated if clinically indicated. If after a rapid evaluation, Zika or other arthropod-borne diseases are the only concern, isolation (contact, droplet, airborne) is unnecessary. Zika is a reportable disease and thus appropriate health authorities must be notified. The modified 3I tool will facilitate rapid analysis and triggering of appropriate actions for patients presenting to the ED at risk for Zika.",2016 May 4,"['Koenig, Kristi L.', 'Almadhyan, Abdulmajeed', 'Burns, Michael J.']",West J Emerg Med,,,True
e788ce631ca8a7d0a0d0b48dfd06d343de282972,PMC,The Ebola Virus Disease Outbreak in West Africa: A Wake-up Call to Revitalize Implementation of the International Health Regulations,http://dx.doi.org/10.3389/fpubh.2016.00120,PMC4899437,27376056,CC BY,"The 2014/15 Ebola virus disease (EVD) outbreak in West Africa has highlighted the inherent weaknesses associated with the implementation of the International Health Regulations (IHR). In this perspective article, the lessons learnt from the outbreak are used to review the challenges impeding effective implementation of the IHR and to propose policy and strategic options for enhancing its application. While some progress has been achieved in implementing the IHR in several countries, numerous challenges continue to impede its effectiveness, especially in developing countries, such as those affected by the West Africa EVD outbreak. Political and economic sensitivities associated with reporting public health emergencies of international concern (PHEIC), inadequate resources (human and financial), and lack of technical know-how required for implementation of the IHR are weaknesses that continue to constrain the implementation of the regulations. In view of the complex sociopolitical, cultural, and public health dimensions of PHEICs, frameworks, such as the IHR, which have legal backing, seem to be the most effective and sustainable option for assuring timely detection, notification, and response to such events. Renewed efforts to strengthen national and global institutional frameworks for implementation of the IHR are therefore required. Improvements in transparency, commitment, and accountability of parties to the IHR, mainstreaming of the IHR into national public health governance structures, use of multidisciplinary approaches, and mobilization of the required resources for the implementation of the IHR are imperative.",2016 Jun 9,"Olu, Olushayo Oluseun",Front Public Health,,,True
491f000353cbe2d030d16077ecb01f02d7c6bf3f,PMC,Development of a Rapid Point-of-Use DNA Test for the Screening of Genuity® Roundup Ready 2 Yield® Soybean in Seed Samples,http://dx.doi.org/10.1155/2016/3145921,PMC4899603,27314015,CC BY,"Testing for the presence of genetically modified material in seed samples is of critical importance for all stakeholders in the agricultural industry, including growers, seed manufacturers, and regulatory bodies. While rapid antibody-based testing for the transgenic protein has fulfilled this need in the past, the introduction of new variants of a given transgene demands new diagnostic regimen that allows distinguishing different traits at the nucleic acid level. Although such molecular tests can be performed by PCR in the laboratory, their requirement for expensive equipment and sophisticated operation have prevented its uptake in point-of-use applications. A recently developed isothermal DNA amplification technique, recombinase polymerase amplification (RPA), combines simple sample preparation and amplification work-flow procedures with the use of minimal detection equipment in real time. Here, we report the development of a highly sensitive and specific RPA-based detection system for Genuity Roundup Ready 2 Yield (RR2Y) material in soybean (Glycine max) seed samples and present the results of studies applying the method in both laboratory and field-type settings.",2016 May 26,"['Chandu, Dilip', 'Paul, Sudakshina', 'Parker, Mathew', 'Dudin, Yelena', 'King-Sitzes, Jennifer', 'Perez, Tim', 'Mittanck, Don W.', 'Shah, Manali', 'Glenn, Kevin C.', 'Piepenburg, Olaf']",Biomed Res Int,,,True
2aabf3a6ba52bfdd83a884673fd6e48c67b8727b,PMC,Host genetics determine susceptibility to avian influenza infection and transmission dynamics,http://dx.doi.org/10.1038/srep26787,PMC4899695,27279280,CC BY,"Host-genetic control of influenza virus infection has been the object of little attention. In this study we determined that two inbred lines of chicken differing in their genetic background , Lines 0 and C-B12, were respectively relatively resistant and susceptible to infection with the low pathogenicity influenza virus A/Turkey/England/647/77 as defined by substantial differences in viral shedding trajectories. Resistant birds, although infected, were unable to transmit virus to contact birds, as ultimately only the presence of a sustained cloacal shedding (and not oropharyngeal shedding) was critical for transmission. Restriction of within-bird transmission of virus occurred in the resistant line, with intra-nares or cloacal infection resulting in only local shedding and failing to transmit fully through the gastro-intestinal-pulmonary tract. Resistance to infection was independent of adaptive immune responses, including the expansion of specific IFNγ secreting cells or production of influenza-specific antibody. Genetic resistance to a novel H9N2 virus was less robust, though significant differences between host genotypes were still clearly evident. The existence of host-genetic determination of the outcome of influenza infection offers tools for the further dissection of this regulation and also for understanding the mechanisms of influenza transmission within and between birds.",2016 Jun 9,"['Ruiz-Hernandez, Raul', 'Mwangi, William', 'Peroval, Marylene', 'Sadeyen, Jean-Remy', 'Ascough, Stephanie', 'Balkissoon, Devanand', 'Staines, Karen', 'Boyd, Amy', 'McCauley, John', 'Smith, Adrian', 'Butter, Colin']",Sci Rep,,,True
f5c62862db786a73879e9160076587d107dbe6e8,PMC,Host genetics determine susceptibility to avian influenza infection and transmission dynamics,http://dx.doi.org/10.1038/srep26787,PMC4899695,27279280,CC BY,"Host-genetic control of influenza virus infection has been the object of little attention. In this study we determined that two inbred lines of chicken differing in their genetic background , Lines 0 and C-B12, were respectively relatively resistant and susceptible to infection with the low pathogenicity influenza virus A/Turkey/England/647/77 as defined by substantial differences in viral shedding trajectories. Resistant birds, although infected, were unable to transmit virus to contact birds, as ultimately only the presence of a sustained cloacal shedding (and not oropharyngeal shedding) was critical for transmission. Restriction of within-bird transmission of virus occurred in the resistant line, with intra-nares or cloacal infection resulting in only local shedding and failing to transmit fully through the gastro-intestinal-pulmonary tract. Resistance to infection was independent of adaptive immune responses, including the expansion of specific IFNγ secreting cells or production of influenza-specific antibody. Genetic resistance to a novel H9N2 virus was less robust, though significant differences between host genotypes were still clearly evident. The existence of host-genetic determination of the outcome of influenza infection offers tools for the further dissection of this regulation and also for understanding the mechanisms of influenza transmission within and between birds.",2016 Jun 9,"['Ruiz-Hernandez, Raul', 'Mwangi, William', 'Peroval, Marylene', 'Sadeyen, Jean-Remy', 'Ascough, Stephanie', 'Balkissoon, Devanand', 'Staines, Karen', 'Boyd, Amy', 'McCauley, John', 'Smith, Adrian', 'Butter, Colin']",Sci Rep,,,False
c8ca3a5306db10a7842b853031404ecbc0a363ed,PMC,"Genetic diversity, seasonality and transmission network of human metapneumovirus: identification of a unique sub-lineage of the fusion and attachment genes",http://dx.doi.org/10.1038/srep27730,PMC4899729,27279080,CC BY,"Human metapneumovirus (HMPV) is an important viral respiratory pathogen worldwide. Current knowledge regarding the genetic diversity, seasonality and transmission dynamics of HMPV among adults and children living in tropical climate remains limited. HMPV prevailed at 2.2% (n = 86/3,935) among individuals presented with acute respiratory tract infections in Kuala Lumpur, Malaysia between 2012 and 2014. Seasonal peaks were observed during the northeast monsoon season (November–April) and correlated with higher relative humidity and number of rainy days (P < 0.05). Phylogenetic analysis of the fusion and attachment genes identified the co-circulation of three known HMPV sub-lineages, A2b and B1 (30.2% each, 26/86) and B2 (20.9%, 18/86), with genotype shift from sub-lineage B1 to A2b observed in 2013. Interestingly, a previously unrecognized sub-lineage of A2 was identified in 18.6% (16/86) of the population. Using a custom script for network construction based on the TN93 pairwise genetic distance, we identified up to nine HMPV transmission clusters circulating as multiple sub-epidemics. Although no apparent major outbreak was observed, the increased frequency of transmission clusters (dyads) during seasonal peaks suggests the potential roles of transmission clusters in driving the spread of HMPV. Our findings provide essential information for therapeutic research, prevention strategies, and disease outbreak monitoring of HMPV.",2016 Jun 9,"['Chow, Wei Zhen', 'Chan, Yoke Fun', 'Oong, Xiang Yong', 'Ng, Liang Jie', 'Nor’E, Siti Sarah', 'Ng, Kim Tien', 'Chan, Kok Gan', 'Hanafi, Nik Sherina', 'Pang, Yong Kek', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Sci Rep,,,True
02a336a36902a4f44b72a881267d77fc79fd7da1,PMC,"Genetic diversity, seasonality and transmission network of human metapneumovirus: identification of a unique sub-lineage of the fusion and attachment genes",http://dx.doi.org/10.1038/srep27730,PMC4899729,27279080,CC BY,"Human metapneumovirus (HMPV) is an important viral respiratory pathogen worldwide. Current knowledge regarding the genetic diversity, seasonality and transmission dynamics of HMPV among adults and children living in tropical climate remains limited. HMPV prevailed at 2.2% (n = 86/3,935) among individuals presented with acute respiratory tract infections in Kuala Lumpur, Malaysia between 2012 and 2014. Seasonal peaks were observed during the northeast monsoon season (November–April) and correlated with higher relative humidity and number of rainy days (P < 0.05). Phylogenetic analysis of the fusion and attachment genes identified the co-circulation of three known HMPV sub-lineages, A2b and B1 (30.2% each, 26/86) and B2 (20.9%, 18/86), with genotype shift from sub-lineage B1 to A2b observed in 2013. Interestingly, a previously unrecognized sub-lineage of A2 was identified in 18.6% (16/86) of the population. Using a custom script for network construction based on the TN93 pairwise genetic distance, we identified up to nine HMPV transmission clusters circulating as multiple sub-epidemics. Although no apparent major outbreak was observed, the increased frequency of transmission clusters (dyads) during seasonal peaks suggests the potential roles of transmission clusters in driving the spread of HMPV. Our findings provide essential information for therapeutic research, prevention strategies, and disease outbreak monitoring of HMPV.",2016 Jun 9,"['Chow, Wei Zhen', 'Chan, Yoke Fun', 'Oong, Xiang Yong', 'Ng, Liang Jie', 'Nor’E, Siti Sarah', 'Ng, Kim Tien', 'Chan, Kok Gan', 'Hanafi, Nik Sherina', 'Pang, Yong Kek', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Sci Rep,,,False
c726b09add3a385ad9b4fa87e54130d78194dcd2,PMC,Duck gut viral metagenome analysis captures snapshot of viral diversity,http://dx.doi.org/10.1186/s13099-016-0113-5,PMC4899906,27284287,CC BY,"BACKGROUND: Ducks (Anas platyrhynchos) an economically important waterfowl for meat, eggs and feathers; is also a natural reservoir for influenza A viruses. The emergence of novel viruses is attributed to the status of co-existence of multiple types and subtypes of viruses in the reservoir hosts. For effective prediction of future viral epidemic or pandemic an in-depth understanding of the virome status in the key reservoir species is highly essential. METHODS: To obtain an unbiased measure of viral diversity in the enteric tract of ducks by viral metagenomic approach, we deep sequenced the viral nucleic acid extracted from cloacal swabs collected from the flock of 23 ducks which shared the water bodies with wild migratory birds. RESULT: In total 7,455,180 reads with average length of 146 bases were generated of which 7,354,300 reads were de novo assembled into 24,945 contigs with an average length of 220 bases and the remaining 100,880 reads were singletons. The duck virome were identified by sequence similarity comparisons of contigs and singletons (BLASTx E score, <10(−3)) against viral reference database. Numerous duck virome sequences were homologous to the animal virus of the Papillomaviridae family; and phages of the Caudovirales, Inoviridae, Tectiviridae, Microviridae families and unclassified phages. Further, several duck virome sequences had homologous with the insect viruses of the Poxviridae, Alphatetraviridae, Baculoviridae, Densovirinae, Iflaviridae and Dicistroviridae families; and plant viruses of the Secoviridae, Virgaviridae, Tombusviridae and Partitiviridae families, which reflects the diet and habitation of ducks. CONCLUSION: This study increases our understanding of the viral diversity and expands the knowledge about the spectrum of viruses harboured in the enteric tract of ducks.",2016 Jun 9,"['Fawaz, Mohammed', 'Vijayakumar, Periyasamy', 'Mishra, Anamika', 'Gandhale, Pradeep N.', 'Dutta, Rupam', 'Kamble, Nitin M.', 'Sudhakar, Shashi B.', 'Roychoudhary, Parimal', 'Kumar, Himanshu', 'Kulkarni, Diwakar D.', 'Raut, Ashwin Ashok']",Gut Pathog,,,True
3c51c5a11684d15c9f3d39dc99b0fdf9f7a73847,PMC,Cybercare 2.0: meeting the challenge of the global burden of disease in 2030,http://dx.doi.org/10.1007/s12553-016-0132-8,PMC4901101,27358760,CC BY,"In this paper, we propose to advance and transform today’s healthcare system using a model of networked health care called Cybercare. Cybercare means “health care in cyberspace” — for example, doctors consulting with patients via videoconferencing across a distributed network; or patients receiving care locally — in neighborhoods, “minute clinics,” and homes — using information technologies such as telemedicine, smartphones, and wearable sensors to link to tertiary medical specialists. This model contrasts with traditional health care, in which patients travel (often a great distance) to receive care from providers in a central hospital. The Cybercare model shifts health care provision from hospital to home; from specialist to generalist; and from treatment to prevention. Cybercare employs advanced technology to deliver services efficiently across the distributed network — for example, using telemedicine, wearable sensors and cell phones to link patients to specialists and upload their medical data in near-real time; using information technology (IT) to rapidly detect, track, and contain the spread of a global pandemic; or using cell phones to manage medical care in a disaster situation. Cybercare uses seven “pillars” of technology to provide medical care: genomics; telemedicine; robotics; simulation, including virtual and augmented reality; artificial intelligence (AI), including intelligent agents; the electronic medical record (EMR); and smartphones. All these technologies are evolving and blending. The technologies are integrated functionally because they underlie the Cybercare network, and/or form part of the care for patients using that distributed network. Moving health care provision to a networked, distributed model will save money, improve outcomes, facilitate access, improve security, increase patient and provider satisfaction, and may mitigate the international global burden of disease. In this paper we discuss how Cybercare is being implemented now, and envision its growth by 2030.",2016 May 27,"['Rosen, Joseph M.', 'Kun, Luis', 'Mosher, Robyn E.', 'Grigg, Elliott', 'Merrell, Ronald C.', 'Macedonia, Christian', 'Klaudt-Moreau, Julien', 'Price-Smith, Andrew', 'Geiling, James']",Health Technol (Berl),,,True
3660a0a14f82558378797b8a86fb7d0854bd1ab4,PMC,Porcine epidemic diarrhea virus (PEDV) detection and antibody response in commercial growing pigs,http://dx.doi.org/10.1186/s12917-016-0725-5,PMC4902975,27287624,CC BY,"BACKGROUND: Longitudinal samples from two production sites were used to (1) describe the pattern of PEDV shedding (rRT-PCR) in individual rectal swabs, pen fecal samples, and pen oral fluids (OF); (2) describe the kinetics of PEDV antibody by ELISA (IgA, IgG) testing of pig serum and pen oral fluid samples; and (3) establish cutoffs and performance estimates for PEDV WV ELISAs (IgA, IgG). Site One was PEDV positive; Site Two was PEDV negative. On Site One, pen samples (feces and oral fluids) and pig samples (rectal swabs and sera) were collected both before and after the population was exposed to PEDV. RESULTS: On Site Two, pen oral fluid samples and individual pig serum samples were negative for both PEDV antibody and nucleic acid. On Site One, PEDV was detected by rRT-PCR at 6 days post exposure (DPE) in all sample types. The last rRT-PCR positives were detected in rectal swabs and oral fluids on 69 DPE. IgG and IgA were detected in oral fluids and serum samples by 13 DPE. Analysis of the PEDV serum IgG WV ELISA data showed that a sample-to-positive (S/P) cutoff of ≥ 0.80 provided a diagnostic sensitivity of 0.87 (95 % CI: 0.82, 0.91) and specificity of 0.99 (95 % CI: 0.98, 1.00). Serum IgG results declined slowly over the monitoring period, with 60 % of serum samples positive (S/P ≥ 0.80) at the final sampling on 111 DPE. Analysis of the PEDV oral fluid IgA WV ELISA found that a cutoff of S/P ≥ 0.80 provided a diagnostic sensitivity of 1.00 (95 % CI: 0.92, 1.00) and a diagnostic specificity of 1.00 (95 % CI: 0.99, 1.00). The oral fluid IgA response increased through 96 DPE and began to decline at the last sampling on 111 DPE. CONCLUSIONS: This study showed that oral fluid-based testing could provide an easy and “animal-friendly” approach to sample collection for nucleic acid and/or antibody-based surveillance of PEDV in swine populations.",2016 Jun 10,"['Bjustrom-Kraft, Jordan', 'Woodard, Katie', 'Giménez-Lirola, Luis', 'Rotolo, Marisa', 'Wang, Chong', 'Sun, Yaxuan', 'Lasley, Peter', 'Zhang, Jianqiang', 'Baum, David', 'Gauger, Phillip', 'Main, Rodger', 'Zimmerman, Jeffrey']",BMC Vet Res,,,True
bca9f4ffe445882f2de559b938d83a69e90d2224,PMC,Etiologic Framework for the Study of Neurodegenerative Disorders as Well as Vascular and Metabolic Comorbidities on the Grounds of Shared Epidemiologic and Biologic Features,http://dx.doi.org/10.3389/fnagi.2016.00138,PMC4904010,27378910,CC BY,"Background: During the last two decades, protein aggregation at all organismal levels, from viruses to humans, has emerged from a neglected area of protein science to become a central issue in biology and biomedicine. This article constitutes a risk-based review aimed at supporting an etiologic scenario of selected, sporadic, protein-associated, i.e., conformational, neurodegenerative disorders (NDDs), and their vascular- and metabolic-associated ailments. Methods: A rationale is adopted, to incorporate selected clinical data and results from animal-model research, complementing epidemiologic evidences reported in two prior articles. Findings: Theory is formulated assuming an underlying conformational transmission mechanism, mediated either by horizontal transfer of mammalian genes coding for specific aggregation-prone proteins, or by xeno-templating between bacterial and host proteins. We build a few population-based and experimentally-testable hypotheses focusing on: (1) non-disposable surgical instruments for sporadic Creutzfeldt-Jakob disease (sCJD) and other rapid progressive neurodegenerative dementia (sRPNDd), multiple system atrophy (MSA), and motor neuron disease (MND); and (2) specific bacterial infections such as B. pertussis and E. coli for all forms, but particularly for late-life sporadic conformational, NDDs, type 2 diabetes mellitus (T2DM), and atherosclerosis where natural protein fibrils present in such organisms as a result of adaptation to the human host induce prion-like mechanisms. Conclusion: Implications for cohort alignment and experimental animal research are discussed and research lines proposed.",2016 Jun 13,"['de Pedro-Cuesta, Jesús', 'Martínez-Martín, Pablo', 'Rábano, Alberto', 'Ruiz-Tovar, María', 'Alcalde-Cabero, Enrique', 'Calero, Miguel']",Front Aging Neurosci,,,True
a8fb2e52e4545f4de90bc13e44ae914d9da6a8ab,PMC,Patient Isolation Precautions: Are They Worth It?,http://dx.doi.org/10.1155/2016/5352625,PMC4904523,27445547,CC BY,"Isolation precautions are intended to minimize pathogen transmission and reduce hospital-acquired infections. More recently, the effectiveness of isolation precautions has been questioned because of increasing evidence of risks. These putative downsides are divided into a quantifiable monetary cost (i.e., a literal cost to the system) and clinically important but less easily quantifiable costs (i.e., “costs” to the patient). The authors also briefly review deisolation and alternatives to isolation. The present review is not arguing against appropriate isolation or precautions, simply that the authors consider both risks and benefits and disseminate up-to-date information. Their patient-focused goal is to mitigate risks for those who truly need isolating and to end isolation as soon as it is safe and appropriate to do so.",2016 Apr 12,"['Sprague, Elliott', 'Reynolds, Steven', 'Brindley, Peter']",Can Respir J,,,True
fd4f419edc4e7a9ee255ea3bdc5b458a86ae4ab3,PMC,Bovine coronavirus in naturally and experimentally exposed calves; viral shedding and the potential for transmission,http://dx.doi.org/10.1186/s12985-016-0555-x,PMC4906604,27296861,CC BY,"BACKGROUND: Bovine coronavirus (BCoV) is a widely distributed pathogen, causing disease and economic losses in the cattle industry worldwide. Prevention of virus spread is impeded by a lack of basic knowledge concerning viral shedding and transmission potential in individual animals. The aims of the study were to investigate the duration and quantity of BCoV shedding in feces and nasal secretions related to clinical signs, the presence of virus in blood and tissues and to test the hypothesis that seropositive calves are not infectious to naïve in-contact calves three weeks after BCoV infection. METHODS: A live animal experiment was conducted, with direct contact between animal groups for 24 h as challenge procedure. Four naïve calves were commingled with a group of six naturally infected calves and sequentially euthanized. Two naïve sentinel calves were commingled with the experimentally exposed group three weeks after exposure. Nasal swabs, feces, blood and tissue samples were analyzed for viral RNA by RT-qPCR, and virus isolation was performed on nasal swabs. Serum was analyzed for BCoV antibodies. RESULTS: The calves showed mild general signs, and the most prominent signs were from the respiratory system. The overall clinical score corresponded well with the shedding of viral RNA the first three weeks after challenge. General depression and cough were the signs that correlated best with shedding of BCoV RNA, while peak respiratory rate and peak rectal temperature appeared more than a week later than the peak shedding. Nasal shedding preceded fecal shedding, and the calves had detectable amounts of viral RNA intermittently in feces through day 35 and in nasal secretions through day 28, however virus isolation was unsuccessful from day six and day 18 from the two calves investigated. Viral RNA was not detected in blood, but was found in lymphatic tissue through day 42 after challenge. Although the calves were shedding BCoV RNA 21 days after infection the sentinel animals were not infected. CONCLUSIONS: Prolonged shedding of BCoV RNA can occur, but detection of viral RNA does not necessarily indicate a transmission potential. The study provides valuable information with regard to producing scientifically based biosecurity advices. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0555-x) contains supplementary material, which is available to authorized users.",2016 Jun 13,"['Oma, Veslemøy Sunniva', 'Tråvén, Madeleine', 'Alenius, Stefan', 'Myrmel, Mette', 'Stokstad, Maria']",Virol J,,,True
e784769ed85685121bda82e89183d0b756686281,PMC,The Impact of Farmers’ Strategic Behavior on the Spread of Animal Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0157450,PMC4907430,27300368,CC BY,"One of the main strategies to control the spread of infectious animal diseases is the implementation of movement restrictions. This paper shows a loss in efficiency of the movement restriction policy (MRP) when behavioral responses of farmers are taken into account. Incorporating the strategic behavior of farmers in an epidemiologic model reveals that the MRP can trigger premature animal sales by farms at high risk of becoming infected that significantly reduce the efficacy of the policy. The results are validated in a parameterized network via Monte Carlo simulations and measures to mitigate the loss of efficiency of the MRP are discussed. Financial aid to farmers can be justified by public health concerns, not only for equity. This paper contributes to developing an interdisciplinary analytical framework regarding the expansion of infectious diseases combining economic and epidemiologic dimensions.",2016 Jun 14,"['Tago, Damian', 'Hammitt, James K.', 'Thomas, Alban', 'Raboisson, Didier']",PLoS One,,,True
52bf83ff771d92f697a4ab0cfe70a99503940050,PMC,Central Role of Ubiquitination in Genome Maintenance: DNA Replication and Damage Repair,http://dx.doi.org/10.5402/2012/146748,PMC4908256,27398234,CC BY,"Faithful transmission of genetic information through generations ensures genomic stability and integrity. However, genetic alterations occur every now and then during the course of genome duplication. In order to repair these genetic defects and lesions, nature has devised several repair pathways which function promptly to prevent the cell from accumulating permanent mutations. These repair mechanisms seem to be significantly impacted by posttranslational modifications of proteins like phosphorylation and ubiquitination. Protein ubiquitination is emerging as a critical regulatory mechanism of DNA damage response. Non-proteolytic, proteasome-independent functions of ubiquitin involving monoubiquitination and polyubiquitination of DNA repair proteins contribute significantly to the signaling of DNA repair pathways. In this paper, we will particularly highlight the work on ubiquitin-mediated signaling in the repair processes involving the Fanconi anemia pathway, translesional synthesis, nucleotide excision repair, and repair of double-strand breaks. We will also discuss the role of ubiquitin ligases in regulating checkpoint mechanisms, the role of deubiquitinating enzymes, and the growing possibilities of therapeutic intervention in this ubiquitin-conjugation system.",2012 Feb 8,"['Ghosh, Soma', 'Saha, Tapas']",ISRN Mol Biol,,,True
b061aea11013896c5d3a9c7c0c4f884397ad38d9,PMC,Animal Models of Cystic Fibrosis Pathology: Phenotypic Parallels and Divergences,http://dx.doi.org/10.1155/2016/5258727,PMC4908263,27340661,CC BY,"Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The resultant characteristic ion transport defect results in decreased mucociliary clearance, bacterial colonisation, and chronic neutrophil-dominated inflammation. Much knowledge surrounding the pathophysiology of the disease has been gained through the generation of animal models, despite inherent limitations in each. The failure of certain mouse models to recapitulate the phenotypic manifestations of human disease has initiated the generation of larger animals in which to study CF, including the pig and the ferret. This review will summarise the basic phenotypes of three animal models and describe the contributions of such animal studies to our current understanding of CF.",2016 Jun 1,"['Lavelle, Gillian M.', 'White, Michelle M.', 'Browne, Niall', 'McElvaney, Noel G.', 'Reeves, Emer P.']",Biomed Res Int,,,True
47d93c4d0e435b2da5ebc11b4404ed209447f5a0,PMC,Angiotensin-converting enzyme 2 prevents lipopolysaccharide-induced rat acute lung injury via suppressing the ERK1/2 and NF-κB signaling pathways,http://dx.doi.org/10.1038/srep27911,PMC4908402,27302421,CC BY,"Acute respiratory distress syndrome (ARDS) caused by severe sepsis remains a major challenge in intensive care medicine. ACE2 has been shown to protect against lung injury. However, the mechanisms of its protective effects on ARDS are largely unknown. Here, we report that ACE2 prevents LPS-induced ARDS by inhibiting MAPKs and NF-κB signaling pathway. Lentiviral packaged Ace2 cDNA or Ace2 shRNA was intratracheally administrated into the lungs of male SD rats. Two weeks after gene transfer, animals received LPS (7.5 mg/Kg) injection alone or in combination with Mas receptor antagonist A779 (10 μg/Kg) or ACE2 inhibitor MLN-4760 (1 mg/Kg) pretreatment. LPS-induced lung injury and inflammatory response were significantly prevented by ACE2 overexpression and deteriorated by Ace2 shRNA. A779 or MLN-4760 pretreatment abolished the protective effects of ACE2. Moreover, overexpression of ACE2 significantly reduced the Ang II/Ang-(1-7) ratio in BALF and up-regulated Mas mRNA expression in lung, which was reversed by A779. Importantly, the blockade of ACE2 on LPS-induced phosphorylation of ERK1/2, p38 and p50/p65 was also abolished by A779. Whereas, only the ERK1/2 inhibitor significantly attenuated lung injury in ACE2 overexpressing rats pretreated with A779. Our observation suggests that AEC2 attenuates LPS-induced ARDS via the Ang-(1-7)/Mas pathway by inhibiting ERK/NF-κB activation.",2016 Jun 15,"['Li, Yingchuan', 'Zeng, Zhen', 'Cao, Yongmei', 'Liu, Yujing', 'Ping, Feng', 'Liang, Mengfan', 'Xue, Ying', 'Xi, Caihua', 'Zhou, Ming', 'Jiang, Wei']",Sci Rep,,,True
0bdae8c38f570965cc9a630a44b7089c2a5da0ed,PMC,Involvement of miR-15a in G0/G1 Phase Cell Cycle Arrest Induced by Porcine Circovirus Type 2 Replication,http://dx.doi.org/10.1038/srep27917,PMC4908419,27302568,CC BY,"Many viruses exploit the host cell division cycle to favour their own growth. Here we demonstrated that porcine circovirus type 2 (PCV2), which is a major causative agent of an emerging and important swine disease complex, PCV2-associated diseases, caused G0/G1 cell cycle arrest through degradation of cyclin D1 and E followed by reduction of retinoblastoma phosphorylation in synchronized PCV2-infected cells dependent upon virus replication. This induction of G0/G1 cell cycle arrest promoted PCV2 replication as evidenced by increased viral protein expression and progeny virus production in the synchronized PCV2-infected cells. To delineate a mechanism of miRNAs in regulating PCV2-induced G0/G1 cell cycle arrest, we determined expression levels of some relevant miRNAs and found that only miR-15a but not miR-16, miR-21, and miR-34a was significantly changed in the PCV2-infected cells. We further demonstrated that upregulation of miR-15a promoted PCV2-induced G0/G1 cell cycle arrest via mediating cyclins D1 and E degradation, in which involves PCV2 growth. These results reveal that G0/G1 cell cycle arrest induced by PCV2 may provide favourable conditions for viral protein expression and progeny production and that miR-15a is implicated in PCV2-induced cell cycle control, thereby contributing to efficient viral replication.",2016 Jun 15,"['Quan, Rong', 'Wei, Li', 'Zhu, Shanshan', 'Wang, Jing', 'Cao, Yongchang', 'Xue, Chunyi', 'Yan, Xu', 'Liu, Jue']",Sci Rep,,,True
06525dbe27937be0f8263a0e8ec743f68d9f1795,PMC,Challenges with using names to link digital biodiversity information,http://dx.doi.org/10.3897/BDJ.4.e8080,PMC4910497,27346955,CC BY,,2016 May 25,"['Patterson, David', 'Mozzherin, Dmitry', 'Shorthouse, David Peter', 'Thessen, Anne']",Biodivers Data J,,,True
7cedb2a5addb854f9c6e833c54e6a352c55a442e,PMC,Fatal canine distemper virus infection of giant pandas in China,http://dx.doi.org/10.1038/srep27518,PMC4910525,27310722,CC BY,"We report an outbreak of canine distemper virus (CDV) infection among endangered giant pandas (Ailuropoda melanoleuca). Five of six CDV infected giant pandas died. The surviving giant panda was previously vaccinated against CDV. Genomic sequencing of CDV isolated from one of the infected pandas (giant panda/SX/2014) suggests it belongs to the Asia-1 cluster. The hemagglutinin protein of the isolated virus and virus sequenced from lung samples originating from deceased giant pandas all possessed the substitutions V26M, T213A, K281R, S300N, P340Q, and Y549H. The presence of the Y549H substitution is notable as it is found at the signaling lymphocytic activation molecule (SLAM) receptor-binding site and has been implicated in the emergence of highly pathogenic CDV and host switching. These findings demonstrate that giant pandas are susceptible to CDV and suggest that surveillance and vaccination among all captive giant pandas are warranted to support conservation efforts for this endangered species.",2016 Jun 16,"['Feng, Na', 'Yu, Yicong', 'Wang, Tiecheng', 'Wilker, Peter', 'Wang, Jianzhong', 'Li, Yuanguo', 'Sun, Zhe', 'Gao, Yuwei', 'Xia, Xianzhu']",Sci Rep,,,True
1385574de3fa0e19e17a0bea94bedebd9c6456e5,PMC,Fatal canine distemper virus infection of giant pandas in China,http://dx.doi.org/10.1038/srep27518,PMC4910525,27310722,CC BY,"We report an outbreak of canine distemper virus (CDV) infection among endangered giant pandas (Ailuropoda melanoleuca). Five of six CDV infected giant pandas died. The surviving giant panda was previously vaccinated against CDV. Genomic sequencing of CDV isolated from one of the infected pandas (giant panda/SX/2014) suggests it belongs to the Asia-1 cluster. The hemagglutinin protein of the isolated virus and virus sequenced from lung samples originating from deceased giant pandas all possessed the substitutions V26M, T213A, K281R, S300N, P340Q, and Y549H. The presence of the Y549H substitution is notable as it is found at the signaling lymphocytic activation molecule (SLAM) receptor-binding site and has been implicated in the emergence of highly pathogenic CDV and host switching. These findings demonstrate that giant pandas are susceptible to CDV and suggest that surveillance and vaccination among all captive giant pandas are warranted to support conservation efforts for this endangered species.",2016 Jun 16,"['Feng, Na', 'Yu, Yicong', 'Wang, Tiecheng', 'Wilker, Peter', 'Wang, Jianzhong', 'Li, Yuanguo', 'Sun, Zhe', 'Gao, Yuwei', 'Xia, Xianzhu']",Sci Rep,,,False
d3c04715d99a379da9cf526b7542f027cf0a04c6,PMC,Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study,http://dx.doi.org/10.1371/journal.pone.0157398,PMC4911076,27309354,CC BY,"OBJECTIVE: Febrile neutropenia is common in children undergoing chemotherapy for the treatment of malignancies. In the majority of cases, the cause of the fever is unknown. Although respiratory viruses are commonly associated with this condition, the etiologic significance of this finding remains unclear and is therefore the subject of this study. STUDY DESIGN: Nasopharyngeal aspirates were collected during 87 episodes of febrile neutropenia in children age 0–18 years, being treated at a children’s oncology unit between January 2013 and June 2014. Real-time polymerase chain reaction was used to determine the presence of 16 respiratory viruses. Follow-up samples were collected from children who tested positive for one or more respiratory viruses. Rhinoviruses were genotyped by VP4/VP2 sequencing. Fisher’s exact test and Mann-Whitney U test were used for group comparisons. RESULTS: At least one respiratory virus was detected in samples from 39 of 87 episodes of febrile neutropenia (45%), with rhinoviruses the most frequently detected. Follow-up samples were collected after a median of 28 days (range, 9–74 days) in 32 of the 39 virus-positive episodes. The respiratory viral infection had resolved in 25 episodes (78%). The same virus was detected at follow-up in one coronavirus and six rhinovirus episodes. Genotyping revealed a different rhinovirus species in two of the six rhinovirus infections. CONCLUSION: The frequency of respiratory viral infections in this group of patients suggests an etiologic role in febrile neutropenia. However, these findings must be confirmed in larger patient cohorts.",2016 Jun 16,"['Söderman, Martina', 'Rhedin, Samuel', 'Tolfvenstam, Thomas', 'Rotzén-Östlund, Maria', 'Albert, Jan', 'Broliden, Kristina', 'Lindblom, Anna']",PLoS One,,,True
a0444a2148ffe99348088aa7c04e21dcea70d602,PMC,Remyelination Is Correlated with Regulatory T Cell Induction Following Human Embryoid Body-Derived Neural Precursor Cell Transplantation in a Viral Model of Multiple Sclerosis,http://dx.doi.org/10.1371/journal.pone.0157620,PMC4911106,27310015,CC BY,"We have recently described sustained clinical recovery associated with dampened neuroinflammation and remyelination following transplantation of neural precursor cells (NPCs) derived from human embryonic stem cells (hESCs) in a viral model of the human demyelinating disease multiple sclerosis. The hNPCs used in that study were derived by a novel direct differentiation method (direct differentiation, DD-NPCs) that resulted in a unique gene expression pattern when compared to hNPCs derived by conventional methods. Since the therapeutic potential of human NPCs may differ greatly depending on the method of derivation and culture, we wanted to determine whether NPCs differentiated using conventional methods would be similarly effective in improving clinical outcome under neuroinflammatory demyelinating conditions. For the current study, we utilized hNPCs differentiated from a human induced pluripotent cell line via an embryoid body intermediate stage (EB-NPCs). Intraspinal transplantation of EB-NPCs into mice infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) resulted in decreased accumulation of CD4+ T cells in the central nervous system that was concomitant with reduced demyelination at the site of injection. Dampened neuroinflammation and remyelination was correlated with a transient increase in CD4+FOXP3+ regulatory T cells (Tregs) concentrated within the peripheral lymphatics. However, compared to our earlier study, pathological improvements were modest and did not result in significant clinical recovery. We conclude that the genetic signature of NPCs is critical to their effectiveness in this model of viral-induced neurologic disease. These comparisons will be useful for understanding what factors are critical for the sustained clinical improvement.",2016 Jun 16,"['Plaisted, Warren C.', 'Zavala, Angel', 'Hingco, Edna', 'Tran, Ha', 'Coleman, Ronald', 'Lane, Thomas E.', 'Loring, Jeanne F.', 'Walsh, Craig M.']",PLoS One,,,True
4cfaea8e65d7e5f6884cffa4055f7f0b48ca164c,PMC,Induction of Apoptosis by the Nonstructural Protein 4 and 10 of Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1371/journal.pone.0156518,PMC4911139,27310256,CC BY,"Infection by most viruses triggers apoptosis in host cells, and viruses manipulate this cell response to promote viral replication, virus spread, and cell killing. Porcine reproductive and respiratory syndrome virus (PRRSV) has been shown to induce apoptosis both in vitro and in vivo, while the regulatory roles of PRRSV-encoded products in apoptosis are not fully understood. In the present study, we first showed a biphasic apoptosis regulation by a highly pathogenic PRRSV strain JXwn06. It was indicated that PRRSV infection delays apoptosis at early infection but activates apoptosis at late infection in MARC-145 cells. In PRRSV-infected MARC-145 cells, procaspase-8, -9 and -12 were activated at late infection, demonstrating the involvements of death receptor pathway, mitochondrial pathway and endoplasmic reticulum (ER) stress pathway in inducing apoptosis. PRRSV was also shown to induce a similar apoptosis process in pulmonary alveolar macrophages (PAMs) with an early initiation. Next, the PRRSV-encoded apoptosis inducers were screened, indicating that the nonstructural protein (Nsp) 4 and Nsp10 of PRRSV are pro-apoptotic. In the presence of Nsp4, it was confirmed that procaspase-8, -9 and -12 were cleaved, and Nsp4 facilitates the cleavage of procaspase-9 by activating B-cell lymphoma 2 interacting mediator of cell death (Bim), a pro-apoptotic protein. In addition, Nsp4 was shown to induce the degradation of an anti-apoptotic protein, B-cell lymphoma-extra large (Bcl-xL). Nsp10 was shown to activate procaspase-8 and -9 but procaspase-12 and to upregulate the expression of BH3-only pro-apoptotic protein BH3 interacting-domain death agonist (Bid) and its active form, truncated Bid (tBid). Clearly, the participation of both activated caspase-8 and Bid is required for Nsp10-induced apoptosis, indicating a crosstalk between extrinsic- and mitochondria-dependent pathways. Together, our findings suggest that PRRSV infection regulates apoptosis in a two-phase manner and activates all three apoptotic pathways; the Nsp4 and Nsp10 of PRRSV function as apoptosis inducers with different molecular basis.",2016 Jun 16,"['Yuan, Shuaizhen', 'Zhang, Ning', 'Xu, Lei', 'Zhou, Lei', 'Ge, Xinna', 'Guo, Xin', 'Yang, Hanchun']",PLoS One,,,True
f0cbe63a26a901e5873aefd4c01faaa078c89c81,PMC,Induction of Apoptosis by the Nonstructural Protein 4 and 10 of Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1371/journal.pone.0156518,PMC4911139,27310256,CC BY,"Infection by most viruses triggers apoptosis in host cells, and viruses manipulate this cell response to promote viral replication, virus spread, and cell killing. Porcine reproductive and respiratory syndrome virus (PRRSV) has been shown to induce apoptosis both in vitro and in vivo, while the regulatory roles of PRRSV-encoded products in apoptosis are not fully understood. In the present study, we first showed a biphasic apoptosis regulation by a highly pathogenic PRRSV strain JXwn06. It was indicated that PRRSV infection delays apoptosis at early infection but activates apoptosis at late infection in MARC-145 cells. In PRRSV-infected MARC-145 cells, procaspase-8, -9 and -12 were activated at late infection, demonstrating the involvements of death receptor pathway, mitochondrial pathway and endoplasmic reticulum (ER) stress pathway in inducing apoptosis. PRRSV was also shown to induce a similar apoptosis process in pulmonary alveolar macrophages (PAMs) with an early initiation. Next, the PRRSV-encoded apoptosis inducers were screened, indicating that the nonstructural protein (Nsp) 4 and Nsp10 of PRRSV are pro-apoptotic. In the presence of Nsp4, it was confirmed that procaspase-8, -9 and -12 were cleaved, and Nsp4 facilitates the cleavage of procaspase-9 by activating B-cell lymphoma 2 interacting mediator of cell death (Bim), a pro-apoptotic protein. In addition, Nsp4 was shown to induce the degradation of an anti-apoptotic protein, B-cell lymphoma-extra large (Bcl-xL). Nsp10 was shown to activate procaspase-8 and -9 but procaspase-12 and to upregulate the expression of BH3-only pro-apoptotic protein BH3 interacting-domain death agonist (Bid) and its active form, truncated Bid (tBid). Clearly, the participation of both activated caspase-8 and Bid is required for Nsp10-induced apoptosis, indicating a crosstalk between extrinsic- and mitochondria-dependent pathways. Together, our findings suggest that PRRSV infection regulates apoptosis in a two-phase manner and activates all three apoptotic pathways; the Nsp4 and Nsp10 of PRRSV function as apoptosis inducers with different molecular basis.",2016 Jun 16,"['Yuan, Shuaizhen', 'Zhang, Ning', 'Xu, Lei', 'Zhou, Lei', 'Ge, Xinna', 'Guo, Xin', 'Yang, Hanchun']",PLoS One,,,False
3fa2c03259615e7a062deaac928c626c0a1bfbf7,PMC,Pharmacologic Inhibition of Host Phosphodiesterase-4 Improves Isoniazid-Mediated Clearance of Mycobacterium tuberculosis,http://dx.doi.org/10.3389/fimmu.2016.00238,PMC4911353,27379099,CC BY,"The lengthy duration of multidrug therapy needed to cure tuberculosis (TB) poses significant challenges for global control of the disease. Moreover, chronic inflammation associated with TB leads to pulmonary damage that can remain even after successful cure. Thus, there is a great need for the development of effective shorter drug regimens to improve clinical outcome and strengthen TB control. Host-directed therapy (HDT) is emerging as a novel adjunctive strategy to enhance the efficacy and shorten the duration of TB treatment. Previously, we showed that the administration of CC-3052, a phosphodiesterase-4 inhibitor (PDE4i), reduced the host inflammatory response during Mycobacterium tuberculosis (Mtb) infection and improved the antimicrobial efficacy of isoniazid (INH) in both the mouse and rabbit models. In the present study, we evaluated the pharmacokinetics and explored the mechanism underlying the efficacy of a more potent PDE4i, CC-11050, as adjunct to INH treatment in a mouse model of pulmonary Mtb infection. Genome-wide lung transcriptome analysis confirmed the dampening of inflammation and associated network genes that we previously reported with CC-3052. Consistent with the reduction in inflammation, a significant improvement in Mtb control and pathology was observed in the lungs of mice treated with CC-11050 plus INH, compared to INH alone. This important confirmatory study will be used to help design upcoming human clinical trials with CC-11050 as an HDT for TB treatment.",2016 Jun 17,"['Subbian, Selvakumar', 'Koo, Mi-Sun', 'Tsenova, Liana', 'Khetani, Vikram', 'Zeldis, Jerome B.', 'Fallows, Dorothy', 'Kaplan, Gilla']",Front Immunol,,,True
50adcf9bfee16b95201df9fdcc9dcf30c1f8ea6e,PMC,In Vitro and In Vivo Attenuation of Vesicular Stomatitis Virus (VSV) by Phosphoprotein Deletion,http://dx.doi.org/10.1371/journal.pone.0157287,PMC4912100,27315286,CC BY,"Vesicular stomatitis virus (VSV) is highly immunogenic and able to stimulate both innate and adaptive immune responses. However, its ability to induce adverse effects has held back the use of VSV as a potential vaccine vector. In this study we developed VSV-ΔP, a safe yet potent replication-defective recombinant VSV in which the phosphoprotein (P) gene was deleted. VSV-ΔP replicated only in supporting cells expressing P (BHK-P cells) and at levels more than 2 logs lower than VSV. In vivo studies indicated that the moderate replication of VSV-ΔP in vitro was associated with the attenuation of this virus in the mouse model, whereas mice intracranially injected with VSV succumbed to neurotoxicity. Furthermore, we constructed VSV and VSV-ΔP expressing a variety of antigens including hemagglutinin-neuraminidase (HN) from Newcastle disease virus (NDV), hemagglutinin (HA) from either a 2009 H1N1 pandemic influenza virus (pdm/09) or the avian H7N9. VSV and VSV-ΔP incorporated the foreign antigens on their surface resulting in induction of robust neutralizing antibody, serum IgG, and hemagglutination inhibition (HAI) titers against their corresponding viruses. These results indicated that VSV with P gene deletion was attenuated in vitro and in vivo, and possibly expressed the foreign antigen on its surface. Therefore, the P gene-deletion strategy may offer a potentially useful and safer approach for attenuating negative-sense RNA viruses which use phosphoprotein as a cofactor for viral replication.",2016 Jun 17,"['Wongthida, Phonphimon', 'Jengarn, Juggragarn', 'Narkpuk, Jaraspim', 'Koonyosying, Pongpisid', 'Srisutthisamphan, Kanjana', 'Wanitchang, Asawin', 'Leaungwutiwong, Pornsawan', 'Teeravechyan, Samaporn', 'Jongkaewwattana, Anan']",PLoS One,,,True
ec317e9df67d2d7fba6904163bd6f69a79380d73,PMC,Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF),http://dx.doi.org/10.1371/journal.pone.0157034,PMC4912142,27314851,CC BY,"Necrotizing enterocolitis (NEC) is a devastating condition of premature infants that results from the gut microbiome invading immature intestinal tissues. This results in a life-threatening disease that is frequently treated with the surgical removal of diseased and dead tissues. Epidermal growth factor (EGF), typically found in bodily fluids, such as amniotic fluid, salvia and mother’s breast milk, is an intestinotrophic growth factor and may reduce the onset of NEC in premature infants. We have produced human EGF in soybean seeds to levels biologically relevant and demonstrated its comparable activity to commercially available EGF. Transgenic soybean seeds expressing a seed-specific codon optimized gene encoding of the human EGF protein with an added ER signal tag at the N’ terminal were produced. Seven independent lines were grown to homozygous and found to accumulate a range of 6.7 +/- 3.1 to 129.0 +/- 36.7 μg EGF/g of dry soybean seed. Proteomic and immunoblot analysis indicates that the inserted EGF is the same as the human EGF protein. Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. This work demonstrates the feasibility of using soybean seeds as a biofactory to produce therapeutic agents in a soymilk delivery platform.",2016 Jun 17,"['He, Yonghua', 'Schmidt, Monica A.', 'Erwin, Christopher', 'Guo, Jun', 'Sun, Raphael', 'Pendarvis, Ken', 'Warner, Brad W.', 'Herman, Eliot M.']",PLoS One,,,True
6f66ba164fba7cd9449ae02d511e2ae8c32b53e4,PMC,High detection rate of dog circovirus in diarrheal dogs,http://dx.doi.org/10.1186/s12917-016-0722-8,PMC4912760,27315792,CC BY,"BACKGROUND: Diarrhea is one of the most common clinical symptoms reported in companion animal clinics. Dog circovirus (DogCV) is a new mammalian circovirus that is considered to be a cause of alimentary syndromes such as diarrhea, vomiting and hemorrhagic enteritis. DogCV has previously only been identified in the United States, Italy, Germany (GeneBank accession number: KF887949) and China (GeneBank accession number: KT946839). Therefore, the aims of this study were to determine the prevalence of DogCV in Taiwan and to explore the correlation between diarrhea and DogCV infection. Clinical specimens were collected between 2012 and 2014 from 207 dogs suffering from diarrhea and 160 healthy dogs. RESULTS: In this study, we developed a sensitive and specific SYBR Green-based real-time PCR assays to detected DogCV in naturally infected animals. Of the analyzed fecal samples from diarrheal dogs and health dogs, 58 (28.0 %) and 19 (11.9 %), respectively, were DogCV positive. The difference in DogCV prevalence was highly significant (P = 0.0002755) in diarrheal dogs. CONCLUSIONS: This is the first study to reveal that DogCV is currently circulating in domestic dogs in Taiwan and to demonstrate its high detection rate in dogs with diarrhea. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0722-8) contains supplementary material, which is available to authorized users.",2016 Jun 17,"['Hsu, Han-Siang', 'Lin, Ting-Han', 'Wu, Hung-Yi', 'Lin, Lee-Shuan', 'Chung, Cheng-Shu', 'Chiou, Ming-Tang', 'Lin, Chao-Nan']",BMC Vet Res,,,True
cdc7a84bccdf6a66bb0e2c902a818aa09ffabfc9,PMC,Tanreqing Injection Attenuates Lipopolysaccharide-Induced Airway Inflammation through MAPK/NF-κB Signaling Pathways in Rats Model,http://dx.doi.org/10.1155/2016/5292346,PMC4913016,27366191,CC BY,"Background. Tanreqing injection (TRQ) is a commonly used herbal patent medicine for treating inflammatory airway diseases in view of its outstanding anti-inflammatory properties. In this study, we explored the signaling pathways involved in contributions of TRQ to LPS-induced airway inflammation in rats. Methods/Design. Adult male Sprague Dawley (SD) rats randomly divided into different groups received intratracheal instillation of LPS and/or intraperitoneal injection of TRQ. Bronchoalveolar Lavage Fluid (BALF) and lung samples were collected at 24 h, 48 h, and 96 h after TRQ administration. Protein and mRNA levels of tumor necrosis factor- (TNF-) α, Interleukin- (IL-) 1β, IL-6, and IL-8 in BALF and lung homogenate were observed by ELISA and real-time PCR, respectively. Lung sections were stained for p38 MAPK and NF-κB detection by immunohistochemistry. Phospho-p38 MAPK, phosphor-extracellular signal-regulated kinases ERK1/2, phospho-SAPK/JNK, phospho-NF-κB p65, phospho-IKKα/β, and phospho-IκB-α were measured by western blot analysis. Results. The results showed that TRQ significantly counteracted LPS-stimulated release of TNF-α, IL-1β, IL-6, and IL-8, attenuated cells influx in BALF, mitigated mucus hypersecretion, suppressed phosphorylation of NF-κB p65, IκB-α, ΙKKα/β, ERK1/2, JNK, and p38 MAPK, and inhibited p38 MAPK and NF-κB p65 expression in rat lungs. Conclusions. Results of the current research indicate that TRQ possesses potent exhibitory effects in LPS-induced airway inflammation by, at least partially, suppressing the MAPKs and NF-κB signaling pathways, in a general dose-dependent manner.",2016 Jun 5,"['Liu, Wei', 'Jiang, Hong-li', 'Cai, Lin-li', 'Yan, Min', 'Dong, Shou-jin', 'Mao, Bing']",Evid Based Complement Alternat Med,,,True
ebbe2e390320b9cd9399ba2e7d011df6e953971e,PMC,The epidermal growth factor receptor regulates cofilin activity and promotes transmissible gastroenteritis virus entry into intestinal epithelial cells,http://dx.doi.org/10.18632/oncotarget.7723,PMC4914279,26933809,CC BY,"Transmissible gastroenteritis virus (TGEV), a coronavirus, causes severe diarrhea and high mortality in newborn piglets. The porcine intestinal epithelium is the target of TGEV infection, but the mechanisms that TGEV disrupts the actin cytoskeleton and invades the host epithelium remain largely unknown. We not only found that TGEV infection stimulates F-actin to gather at the cell membrane but the disruption of F-actin inhibits TGEV entry as well. Cofilin is involved in F-actin reorganization and TGEV entry. The TGEV spike protein is capable of binding with EGFR, activating the downstream phosphoinositide-3 kinase (PI3K), then causing the phosphorylation of cofilin and F-actin polymerization via Rac1/Cdc42 GTPases. Inhibition of EGFR and PI3K decreases the entry of TGEV. EGFR is also the upstream activator of mitogen-activated protein kinase (MAPK) signaling pathways that is involved in F-actin reorganization. Additionally, lipid rafts act as signal platforms for the EGFR-associated signaling cascade and correlate with the adhesion of TGEV. In conlusion, these results provide valuable data of the mechanisms which are responsible for the TGEV pathogenesis and may lead to the development of new methods about controlling TGEV.",2016 Feb 25,"['Hu, Weiwei', 'Zhu, Liqi', 'Yang, Xing', 'Lin, Jian', 'Yang, Qian']",Oncotarget,,,True
e5af126d541f65e20bf349843f191730486b0814,PMC,The epidermal growth factor receptor regulates cofilin activity and promotes transmissible gastroenteritis virus entry into intestinal epithelial cells,http://dx.doi.org/10.18632/oncotarget.7723,PMC4914279,26933809,CC BY,"Transmissible gastroenteritis virus (TGEV), a coronavirus, causes severe diarrhea and high mortality in newborn piglets. The porcine intestinal epithelium is the target of TGEV infection, but the mechanisms that TGEV disrupts the actin cytoskeleton and invades the host epithelium remain largely unknown. We not only found that TGEV infection stimulates F-actin to gather at the cell membrane but the disruption of F-actin inhibits TGEV entry as well. Cofilin is involved in F-actin reorganization and TGEV entry. The TGEV spike protein is capable of binding with EGFR, activating the downstream phosphoinositide-3 kinase (PI3K), then causing the phosphorylation of cofilin and F-actin polymerization via Rac1/Cdc42 GTPases. Inhibition of EGFR and PI3K decreases the entry of TGEV. EGFR is also the upstream activator of mitogen-activated protein kinase (MAPK) signaling pathways that is involved in F-actin reorganization. Additionally, lipid rafts act as signal platforms for the EGFR-associated signaling cascade and correlate with the adhesion of TGEV. In conlusion, these results provide valuable data of the mechanisms which are responsible for the TGEV pathogenesis and may lead to the development of new methods about controlling TGEV.",2016 Feb 25,"['Hu, Weiwei', 'Zhu, Liqi', 'Yang, Xing', 'Lin, Jian', 'Yang, Qian']",Oncotarget,,,False
063ac3f62e4657ad610a771fc796bba4f3e404b2,PMC,De Novo Assembly and Comparative Transcriptome Analysis Provide Insight into Lysine Biosynthesis in Toona sinensis Roem,http://dx.doi.org/10.1155/2016/6735209,PMC4914729,27376077,CC BY,"Toona sinensis Roem is a popular leafy vegetable in Chinese cuisine and is also used as a traditional Chinese medicine. In this study, leaf samples were collected from the same plant on two development stages and then used for high-throughput Illumina RNA-sequencing (RNA-Seq). 125,884 transcripts and 54,628 unigenes were obtained through de novo assembly. A total of 25,570 could be annotated with known biological functions, which indicated that the T. sinensis leaves and shoots were undergoing multiple developmental processes especially for active metabolic processes. Analysis of differentially expressed unigenes between the two libraries showed that the lysine biosynthesis was an enriched KEGG pathway, and candidate genes involved in the lysine biosynthesis pathway in T. sinensis leaves and shoots were identified. Our results provide a primary analysis of the gene expression files of T. sinensis leaf and shoot on different development stages and afford a valuable resource for genetic and genomic research on plant lysine biosynthesis.",2016 Jun 7,"['Zhang, Xia', 'Song, Zhenqiao', 'Liu, Tian', 'Guo, Linlin', 'Li, Xingfeng']",Int J Genomics,,,False
8e96ff3220b7201598d2c5099ff9a4d03e529b3b,PMC,De Novo Assembly and Comparative Transcriptome Analysis Provide Insight into Lysine Biosynthesis in Toona sinensis Roem,http://dx.doi.org/10.1155/2016/6735209,PMC4914729,27376077,CC BY,"Toona sinensis Roem is a popular leafy vegetable in Chinese cuisine and is also used as a traditional Chinese medicine. In this study, leaf samples were collected from the same plant on two development stages and then used for high-throughput Illumina RNA-sequencing (RNA-Seq). 125,884 transcripts and 54,628 unigenes were obtained through de novo assembly. A total of 25,570 could be annotated with known biological functions, which indicated that the T. sinensis leaves and shoots were undergoing multiple developmental processes especially for active metabolic processes. Analysis of differentially expressed unigenes between the two libraries showed that the lysine biosynthesis was an enriched KEGG pathway, and candidate genes involved in the lysine biosynthesis pathway in T. sinensis leaves and shoots were identified. Our results provide a primary analysis of the gene expression files of T. sinensis leaf and shoot on different development stages and afford a valuable resource for genetic and genomic research on plant lysine biosynthesis.",2016 Jun 7,"['Zhang, Xia', 'Song, Zhenqiao', 'Liu, Tian', 'Guo, Linlin', 'Li, Xingfeng']",Int J Genomics,,,True
c8d2fa6e178d17b218df59b33cfcb5839af7dc7f,PMC,No involvement of alveolar macrophages in the initiation of carbon nanoparticle induced acute lung inflammation in mice,http://dx.doi.org/10.1186/s12989-016-0144-6,PMC4915176,27328634,CC BY,"BACKGROUND: Carbonaceous nanoparticles (CNP) represent a major constituent of urban particulate air pollution, and inhalation of high CNP levels has been described to trigger a pro-inflammatory response of the lung. While several studies identified specific particle characteristics driving respiratory toxicity of low-solubility and low-toxicity particles such as CNP, the major lung cell type, which initiates and drives that response, remains still uncertain. Since alveolar macrophages (AM) are known to effectively phagocytose inhaled particles and play a crucial role for the initiation of pulmonary inflammation caused by invading microbes, we aimed to determine their role for sterile stimuli such as CNP by profiling the primary alveolar cell compartments of the lung. We exposed C57BL/6 mice to 20 μg CNP by intratracheal instillation and comprehensively investigated the expression of the underlying mediators during a time span of 3 to 72 h in three different lung cell populations: CD45- (negative) structural cells, CD45+ (positive) leukocytes, and by BAL recovered cells. RESULTS: Bronchoalveolar lavage (BAL) analysis revealed an acute inflammatory response characterized by the most prominent culmination of neutrophil granulocytes from 12 to 24 h after instillation, which declined to basal levels by day 7. As early as 3 h after CNP exposure 50 % of the AM revealed particle laden. BAL concentrations and lung gene expression profiles of TNFα, and the neutrophil chemoattractants CXCL1,-2 and-5 preceded the neutrophil recruitment and showed highest levels after 12 h of CNP exposure, pointing to a significant activation of the inflammation-evoking lung cells at this point of time. AM, isolated from lungs 3 to 12 h after CNP instillation, however, did not show a pro-inflammatory signature. On the contrary, gene expression analysis of different lung cell populations isolated 12 h after CNP instillation revealed CD45-, mainly representing alveolar epithelial type II (ATII) cells as major producer of inflammatory CXCL cytokines. Particularly by CD45- cells expressed Cxcl5 proved to be the most abundant chemokine, being 12 h after CNP exposure 24 (±11) fold induced. CONCLUSION: Our data suggests that AM are noninvolved in the initiation of the inflammatory response. ATII cells, which induced highest CXCL levels early on, might in contrast be the driver of acute neutrophilic inflammation upon pulmonary CNP exposure. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-016-0144-6) contains supplementary material, which is available to authorized users.",2016 Jun 21,"['Chen, Shanze', 'Yin, Renfu', 'Mutze, Kathrin', 'Yu, Youjia', 'Takenaka, Shinji', 'Königshoff, Melanie', 'Stoeger, Tobias']",Part Fibre Toxicol,,,True
34c60b33c493dfe1545112d9f4b1107576f11dbd,PMC,No involvement of alveolar macrophages in the initiation of carbon nanoparticle induced acute lung inflammation in mice,http://dx.doi.org/10.1186/s12989-016-0144-6,PMC4915176,27328634,CC BY,"BACKGROUND: Carbonaceous nanoparticles (CNP) represent a major constituent of urban particulate air pollution, and inhalation of high CNP levels has been described to trigger a pro-inflammatory response of the lung. While several studies identified specific particle characteristics driving respiratory toxicity of low-solubility and low-toxicity particles such as CNP, the major lung cell type, which initiates and drives that response, remains still uncertain. Since alveolar macrophages (AM) are known to effectively phagocytose inhaled particles and play a crucial role for the initiation of pulmonary inflammation caused by invading microbes, we aimed to determine their role for sterile stimuli such as CNP by profiling the primary alveolar cell compartments of the lung. We exposed C57BL/6 mice to 20 μg CNP by intratracheal instillation and comprehensively investigated the expression of the underlying mediators during a time span of 3 to 72 h in three different lung cell populations: CD45- (negative) structural cells, CD45+ (positive) leukocytes, and by BAL recovered cells. RESULTS: Bronchoalveolar lavage (BAL) analysis revealed an acute inflammatory response characterized by the most prominent culmination of neutrophil granulocytes from 12 to 24 h after instillation, which declined to basal levels by day 7. As early as 3 h after CNP exposure 50 % of the AM revealed particle laden. BAL concentrations and lung gene expression profiles of TNFα, and the neutrophil chemoattractants CXCL1,-2 and-5 preceded the neutrophil recruitment and showed highest levels after 12 h of CNP exposure, pointing to a significant activation of the inflammation-evoking lung cells at this point of time. AM, isolated from lungs 3 to 12 h after CNP instillation, however, did not show a pro-inflammatory signature. On the contrary, gene expression analysis of different lung cell populations isolated 12 h after CNP instillation revealed CD45-, mainly representing alveolar epithelial type II (ATII) cells as major producer of inflammatory CXCL cytokines. Particularly by CD45- cells expressed Cxcl5 proved to be the most abundant chemokine, being 12 h after CNP exposure 24 (±11) fold induced. CONCLUSION: Our data suggests that AM are noninvolved in the initiation of the inflammatory response. ATII cells, which induced highest CXCL levels early on, might in contrast be the driver of acute neutrophilic inflammation upon pulmonary CNP exposure. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-016-0144-6) contains supplementary material, which is available to authorized users.",2016 Jun 21,"['Chen, Shanze', 'Yin, Renfu', 'Mutze, Kathrin', 'Yu, Youjia', 'Takenaka, Shinji', 'Königshoff, Melanie', 'Stoeger, Tobias']",Part Fibre Toxicol,,,True
0eff8cb176dc1e97612266b1ed94badfeab4e575,PMC,Type I Interferon Receptor Deficiency in Dendritic Cells Facilitates Systemic Murine Norovirus Persistence Despite Enhanced Adaptive Immunity,http://dx.doi.org/10.1371/journal.ppat.1005684,PMC4915689,27327515,CC BY,"In order for a virus to persist, there must be a balance between viral replication and immune clearance. It is commonly believed that adaptive immunity drives clearance of viral infections and, thus, dysfunction or viral evasion of adaptive immunity is required for a virus to persist. Type I interferons (IFNs) play pleiotropic roles in the antiviral response, including through innate control of viral replication. Murine norovirus (MNoV) replicates in dendritic cells (DCs) and type I IFN signaling in DCs is important for early control of MNoV replication. We show here that the non-persistent MNoV strain CW3 persists systemically when CD11c positive DCs are unable to respond to type I IFN. Persistence in this setting is associated with increased early viral titers, maintenance of DC numbers, increased expression of DC activation markers and an increase in CD8 T cell and antibody responses. Furthermore, CD8 T cell function is maintained during the persistent phase of infection and adaptive immune cells from persistently infected mice are functional when transferred to Rag1 (-/-) recipients. Finally, increased early replication and persistence are also observed in mixed bone marrow chimeras where only half of the CD11c positive DCs are unable to respond to type I IFN. These findings demonstrate that increased early viral replication due to a cell-intrinsic innate immune deficiency is sufficient for persistence and a functional adaptive immune response is not sufficient for viral clearance.",2016 Jun 21,"['Nice, Timothy J.', 'Osborne, Lisa C.', 'Tomov, Vesselin T.', 'Artis, David', 'Wherry, E. John', 'Virgin, Herbert W.']",PLoS Pathog,,,True
1af8d169cf2d572b46f2b94b1e83c66686973297,PMC,A comprehensive in silico analysis of non-synonymous and regulatory SNPs of human MBL2 gene,http://dx.doi.org/10.1186/s40064-016-2543-4,PMC4916122,27390651,CC BY,"Mannose binding lectin (MBL) is a liver derived protein which plays an important role in innate immunity. Mannose binding lectin gene 2 (MBL2) polymorphisms are reported to be associated with various diseases. In spite of being exhaustively studied molecule, no attempt has been made till date to comprehensively and systematically analyze the SNPs of MBL2 gene. The present study was carried out to identify and prioritize the SNPs of MBL2 gene for further genotyping and functional studies. To predict the possible impact of SNPs on MBL structure and function SNP data obtained from dbSNP database were analyzed using various bioinformatics tools. Out of total 661 SNPs, only 37 validated SNPs having minor allele frequency ≥0.10 were considered for the present study. These 37 SNPs includes one in 3′ near gene, nine in 3′ UTR, one non-synonymous SNP (nsSNP), thirteen intronic SNPs and thirteen in 5′ near gene. From these 37 SNPs, 11 non-coding SNPs were identified to be of functional significance and evolutionary conserved. Out of these, 4 SNPs from 3′ UTR were found to play role in miRNA binding, 7 SNPs from 5′ near and intronic region were predicted to involve in transcription factor binding and expression of MBL2 gene. One nsSNP Gly54Asp (rs1800450) was found to be deleterious and damaging by both SIFT and Polyphen-2 servers and thus affecting MBL2 protein stability and expression. Protein structural analysis with this amino acid variant was performed by using I-TASSER, RAMPAGE, Swiss-PdbViewer, Chimera and I-mutant. Information regarding solvent accessibility, molecular dynamics and energy minimization calculations showed that this variant causes clashes with neighboring amino acids residues that must interfere in the normal triple helix formation of trimeric subunit and further with the normal assembly of MBL oligomeric form, hence decrease in stability. Thus, findings of the present study indicated 12 SNPs of MBL2 gene to be functionally important. Exploration of these variants may provide novel remedial markers for various diseases.",2016 Jun 21,"['Kalia, Namarta', 'Sharma, Aarti', 'Kaur, Manpreet', 'Kamboj, Sukhdev Singh', 'Singh, Jatinder']",Springerplus,,,True
db5333b01a10f165ae516d30f9d1fbf96ab4b841,PMC,Biological function of Foot-and-mouth disease virus non-structural proteins and non-coding elements,http://dx.doi.org/10.1186/s12985-016-0561-z,PMC4917953,27334704,CC BY,"Foot-and-mouth disease virus (FMDV) represses host translation machinery, blocks protein secretion, and cleaves cellular proteins associated with signal transduction and the innate immune response to infection. Non-structural proteins (NSPs) and non-coding elements (NCEs) of FMDV play a critical role in these biological processes. The FMDV virion consists of capsid and nucleic acid. The virus genome is a positive single stranded RNA and encodes a single long open reading frame (ORF) flanked by a long structured 5ʹ-untranslated region (5ʹ-UTR) and a short 3ʹ-UTR. The ORF is translated into a polypeptide chain and processed into four structural proteins (VP1, VP2, VP3, and VP4), 10 NSPs (L(pro), 2A, 2B, 2C, 3A, 3B(1–3), 3C(pro), and 3D(pol)), and some cleavage intermediates. In the past decade, an increasing number of studies have begun to focus on the molecular pathogenesis of FMDV NSPs and NCEs. This review collected recent research progress on the biological functions of these NSPs and NCEs on the replication and host cellular regulation of FMDV to understand the molecular mechanism of host–FMDV interactions and provide perspectives for antiviral strategy and development of novel vaccines.",2016 Jun 22,"['Gao, Yuan', 'Sun, Shi-Qi', 'Guo, Hui-Chen']",Virol J,,,True
8d27cf597c7bb3029c304801e4413396e8731d4b,PMC,Spatial expansions and travelling waves of rabies in vampire bats,http://dx.doi.org/10.1098/rspb.2016.0328,PMC4920313,,CC BY,"A major obstacle to anticipating the cross-species transmission of zoonotic diseases and developing novel strategies for their control is the scarcity of data informing how these pathogens circulate within natural reservoir populations. Vampire bats are the primary reservoir of rabies in Latin America, where the disease remains among the most important viral zoonoses affecting humans and livestock. Unpredictable spatiotemporal dynamics of rabies within bat populations have precluded anticipation of outbreaks and undermined widespread bat culling programs. By analysing 1146 vampire bat-transmitted rabies (VBR) outbreaks in livestock across 12 years in Peru, we demonstrate that viral expansions into historically uninfected zones have doubled the recent burden of VBR. Viral expansions are geographically widespread, but severely constrained by high elevation peaks in the Andes mountains. Within Andean valleys, invasions form wavefronts that are advancing towards large, unvaccinated livestock populations that are heavily bitten by bats, which together will fuel high transmission and mortality. Using spatial models, we forecast the pathways of ongoing VBR epizootics across heterogeneous landscapes. These results directly inform vaccination strategies to mitigate impending viral emergence, reveal VBR as an emerging rather than an enzootic disease and create opportunities to test novel interventions to manage viruses in bat reservoirs.",2016 Jun 15,"['Benavides, Julio A.', 'Valderrama, William', 'Streicker, Daniel G.']",Proc Biol Sci,,,True
acf562f91614c114eaeec07bae37b8130968d3df,PMC,Spatial expansions and travelling waves of rabies in vampire bats,http://dx.doi.org/10.1098/rspb.2016.0328,PMC4920313,,CC BY,"A major obstacle to anticipating the cross-species transmission of zoonotic diseases and developing novel strategies for their control is the scarcity of data informing how these pathogens circulate within natural reservoir populations. Vampire bats are the primary reservoir of rabies in Latin America, where the disease remains among the most important viral zoonoses affecting humans and livestock. Unpredictable spatiotemporal dynamics of rabies within bat populations have precluded anticipation of outbreaks and undermined widespread bat culling programs. By analysing 1146 vampire bat-transmitted rabies (VBR) outbreaks in livestock across 12 years in Peru, we demonstrate that viral expansions into historically uninfected zones have doubled the recent burden of VBR. Viral expansions are geographically widespread, but severely constrained by high elevation peaks in the Andes mountains. Within Andean valleys, invasions form wavefronts that are advancing towards large, unvaccinated livestock populations that are heavily bitten by bats, which together will fuel high transmission and mortality. Using spatial models, we forecast the pathways of ongoing VBR epizootics across heterogeneous landscapes. These results directly inform vaccination strategies to mitigate impending viral emergence, reveal VBR as an emerging rather than an enzootic disease and create opportunities to test novel interventions to manage viruses in bat reservoirs.",2016 Jun 15,"['Benavides, Julio A.', 'Valderrama, William', 'Streicker, Daniel G.']",Proc Biol Sci,,,True
42bb18ca1f49d74b80f2bab85b3878cade647b08,PMC,Comparison of Thermal and Non-Thermal Processing of Swine Feed and the Use of Selected Feed Additives on Inactivation of Porcine Epidemic Diarrhea Virus (PEDV),http://dx.doi.org/10.1371/journal.pone.0158128,PMC4920390,27341670,CC BY,"Infection with porcine epidemic diarrhea virus (PEDV) causes diarrhea, vomiting, and high mortality in suckling pigs. Contaminated feed has been suggested as a vehicle of transmission for PEDV. The objective of this study was to compare thermal and electron beam processing, and the inclusion of feed additives on the inactivation of PEDV in feed. Feed samples were spiked with PEDV and then heated to 120–145°C for up to 30 min or irradiated at 0–50 kGy. Another set of feed samples spiked with PEDV and mixed with Ultracid P (Nutriad), Activate DA (Novus International), KEM-GEST (Kemin Agrifood), Acid Booster (Agri-Nutrition), sugar or salt was incubated at room temperature (~25°C) for up to 21 days. At the end of incubation, the virus titers were determined by inoculation of Vero-81 cells and the virus inactivation kinetics were modeled using the Weibull distribution model. The Weibull kinetic parameter delta represented the time or eBeam dose required to reduce virus concentration by 1 log. For thermal processing, delta values ranged from 16.52 min at 120°C to 1.30 min at 145°C. For eBeam processing, a target dose of 50 kGy reduced PEDV concentration by 3 log. All additives tested were effective in reducing the survival of PEDV when compared with the control sample (delta = 17.23 days). Activate DA (0.81) and KEM-GEST (3.28) produced the fastest inactivation. In conclusion, heating swine feed at temperatures over 130°C or eBeam processing of feed with a dose over 50 kGy are effective processing steps to reduce PEDV survival. Additionally, the inclusion of selected additives can decrease PEDV survivability.",2016 Jun 24,"['Trudeau, Michaela P.', 'Verma, Harsha', 'Sampedro, Fernando', 'Urriola, Pedro E.', 'Shurson, Gerald C.', 'McKelvey, Jessica', 'Pillai, Suresh D.', 'Goyal, Sagar M.']",PLoS One,,,True
87154b31b741f39ec7e34f3590f80b9a01105e33,PMC,Association between ambient temperature and lower urinary tract symptoms: a community-based survey,http://dx.doi.org/10.1590/S1677-5538.IBJU.2015.0159,PMC4920570,27286116,CC BY,"PURPOSE: The aim of this study was to evaluate the individual change of International prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) in each patient by temperature conditions. MATERIALS AND METHODS: The severity of lower urinary tract symptoms (LUTS) was explored using the IPSS and OABSS questionnaires that were completed by 2.486 subjects (923 males and 1.563 females) aged 60 years and older. Korea Meteorological Administration data was used to determine daily average temperature and daily temperature difference on the interview dates at each site. RESULTS: The mean IPSS and mean age for males was 13.45±8.24 and 75.03±6.20 years, respectively. The mean OABSS and mean age for females was 4.41±3.10 and 73.74±6.03years, respectively. Daily average temperature and daily temperature difference ranged from-3.4-28.3(o)C and 2.2-16.9(o)C, respectively. Age was a significantly risk factor for IPSS, OABSS, and QoL (P<0.001, <0.001, and 0.005, respectively). After multiple regression analysis, daily average temperatures did not show a statistically significant change in IPSS and OABSS. Only daily temperature differences were associated with male LUTS. CONCLUSIONS: While LUTS could be worsened in low temperatures generally, IPSS and OABSS were not affected by daily average temperature conditions. Daily temperature differences may be more influential than daily average temperatures.",2016 May-Jun,"['Shim, Sung Ryul', 'Kim, Jae Heon', 'Won, Jong Ho', 'Song, Eun Seop', 'Song, Yun Seob']",Int Braz J Urol,,,True
cf6dbaad6eab542c67cde5670d0fa0a2a65248f8,PMC,"Alphacoronavirus in urban Molossidae and Phyllostomidae bats, Brazil",http://dx.doi.org/10.1186/s12985-016-0569-4,PMC4920988,27342195,CC BY,"BACKGROUND: Bats have been implicated as the main reservoir of coronavirus (CoV). Thus the role of these hosts on the evolution and spread of CoVs currently deserve the attention of emerging diseases surveillance programs. On the view of the interest on and importance of CoVs in bats the occurrence and molecular characterization of CoV were conducted in bats from Brazil. FINDINGS: Three hundred five enteric contents of 29 bat species were tested using a panCoV nested RT-PCR. Nine specimens were positive and eight was suitable for RdRp gene sequencing. RdRp gene phylogeny showed that all CoVs strains from this study cluster in Alphacoronavirus genus, with one Molossidae and one Phlyllostomidae-CoV specific groups. Phylogenetic analyses of two S gene sequences showed a large diversity within the Alphacoronavirus genus. CONCLUSIONS: This study indicated a CoV-to-host specificity and draws attention for CoV detection in Cynomops sp, a potential new reservoir. The phylogenetic analyses indicate that diversity of CoV in bats is higher than previously known.",2016 Jun 24,"['Asano, Karen Miyuki', 'Hora, Aline Santana', 'Scheffer, Karin Côrrea', 'Fahl, Willian Oliveira', 'Iamamoto, Keila', 'Mori, Enio', 'Brandão, Paulo Eduardo']",Virol J,,,True
7fcbdac915f32c243a9c8bc7cc086b2ac65416af,PMC,Immunity-Related Protein Expression and Pathological Lung Damage in Mice Poststimulation with Ambient Particulate Matter from Live Bird Markets,http://dx.doi.org/10.3389/fimmu.2016.00252,PMC4921493,27446082,CC BY,"The objective of this study was to obtain insight into the adverse health effects of airborne particulate matter (PM) collected from live bird markets and to determine whether biological material in PM accounts for immune-related inflammatory response. Mice were exposed to a single or repeated dose of PM, after which the expression of toll-like receptors (TLRs), cytokines, and chemokines in the lungs of infected mice were examined by enzyme-linked immunosorbent assay and histopathological analysis. Results after single and repeated PM stimulation with [Formula: see text] indicated that TLR2 and TLR4 played a dominant role in the inflammatory responses of the lung. Further analysis demonstrated that the expression levels of IL-1β, TNF-α, IFN-γ, IL-8, IP-10, and MCP-1 increased significantly, which could eventually contribute to lung injury. Moreover, biological components in PM were critical in mediating immune-related inflammatory responses and should therefore not be overlooked.",2016 Jun 27,"['Meng, Kai', 'Wu, Bo', 'Gao, Jing', 'Cai, Yumei', 'Yao, Meiling', 'Wei, Liangmeng', 'Chai, Tongjie']",Front Immunol,,,True
bf001dd7a7e2e974fa974607ccbcd9a2de960d2a,PMC,SARS Coronavirus Fusion Peptide-Derived Sequence Suppresses Collagen-Induced Arthritis in DBA/1J Mice,http://dx.doi.org/10.1038/srep28672,PMC4923882,27349522,CC BY,"During the co-evolution of viruses and their hosts, the viruses have evolved numerous strategies to counter and evade host antiviral immune responses in order to establish a successful infection, replicate and persist in the host. Recently, based on our model of immune signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) model, we suggested specific molecular mechanisms used by different viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) to modulate the host immune response mediated by members of the family of multichain immune recognition receptors (MIRRs). This family includes T cell receptor (TCR) that is critically involved in immune diseases such as autoimmune arthritis. In the present study, we provide compelling experimental in vivo evidence in support of our hypothesis. Using the SCHOOL approach and the SARS-CoV fusion peptide sequence, we rationally designed a novel immunomodulatory peptide that targets TCR. We showed that this peptide ameliorates collagen-induced arthritis in DBA/1J mice and protects against bone and cartilage damage. Incorporation of the peptide into self-assembling lipopeptide nanoparticles that mimic native human high density lipoproteins significantly increases peptide dosage efficacy. Together, our data further confirm that viral immune evasion strategies that target MIRRs can be transferred to therapeutic strategies that require similar functionalities.",2016 Jun 28,"['Shen, Zu T.', 'Sigalov, Alexander B.']",Sci Rep,,,True
455ddc24431c80dc3b027caf22fc7112e30ff89f,PMC,SARS Coronavirus Fusion Peptide-Derived Sequence Suppresses Collagen-Induced Arthritis in DBA/1J Mice,http://dx.doi.org/10.1038/srep28672,PMC4923882,27349522,CC BY,"During the co-evolution of viruses and their hosts, the viruses have evolved numerous strategies to counter and evade host antiviral immune responses in order to establish a successful infection, replicate and persist in the host. Recently, based on our model of immune signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) model, we suggested specific molecular mechanisms used by different viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) to modulate the host immune response mediated by members of the family of multichain immune recognition receptors (MIRRs). This family includes T cell receptor (TCR) that is critically involved in immune diseases such as autoimmune arthritis. In the present study, we provide compelling experimental in vivo evidence in support of our hypothesis. Using the SCHOOL approach and the SARS-CoV fusion peptide sequence, we rationally designed a novel immunomodulatory peptide that targets TCR. We showed that this peptide ameliorates collagen-induced arthritis in DBA/1J mice and protects against bone and cartilage damage. Incorporation of the peptide into self-assembling lipopeptide nanoparticles that mimic native human high density lipoproteins significantly increases peptide dosage efficacy. Together, our data further confirm that viral immune evasion strategies that target MIRRs can be transferred to therapeutic strategies that require similar functionalities.",2016 Jun 28,"['Shen, Zu T.', 'Sigalov, Alexander B.']",Sci Rep,,,False
ec9755d0db388d8a9066baffc9fd33bdf24f5bac,PMC,"Individual Monitoring and Occupational Dose Record Management in China: History, Current Status and Perspectives",http://dx.doi.org/10.3390/ijerph13060558,PMC4924015,27271646,CC BY,"This review paper presents an overview of individual monitoring, as well as the national dose register and dose record management of radiation workers in China. Progress has recently been made on the individual monitoring of radiation workers. A critical analysis of current status and problems in individual monitoring is also presented and necessary future research on individual monitoring, such as the monitoring technology in the form of the ring dosimeters and eye lens dosimeters, is suggested.",2016 Jun 3,"['Wang, Hong-Bo', 'Yu, Hai-Tao', 'Sun, Quan-Fu']",Int J Environ Res Public Health,,,True
365ab3e4ca40537484abf16d4d33d88f63635404,PMC,A Bibliometric Analysis of PubMed Literature on Middle East Respiratory Syndrome,http://dx.doi.org/10.3390/ijerph13060583,PMC4924040,27304963,CC BY,"Middle East Respiratory Syndrome (MERS), a pandemic threat to human beings, has aroused huge concern worldwide, but no bibliometric studies have been conducted on MERS research. The aim of this study was to map research productivity on the disease based on the articles indexed in PubMed. The articles related to MERS dated from 2012 to 2015 were retrieved from PubMed. The articles were classified into three categories according to their focus. Publication outputs were assessed and frequently used terms were mapped using the VOS viewer software. A total of 443 articles were included for analysis. They were published in 162 journals, with Journal of Virology being the most productive (44 articles; 9.9%) and by six types of organizations, with universities being the most productive (276 articles; 62.4%).The largest proportion of the articles focused on basic medical sciences and clinical studies (47.2%) and those on prevention and control ranked third (26.2%), with those on other focuses coming in between (26.6%). The articles on prevention and control had the highest mean rank for impact factor (IF) (226.34), followed by those on basic medical sciences and clinical studies (180.23) and those on other focuses (168.03). The mean rank differences were statistically significant (p = 0.000). Besides, “conronavirus”, “case”, “transmission” and “detection” were found to be the most frequently used terms. The findings of this first bibliometric study on MERS suggest that the prevention and control of the disease has become a big concern and related research should be strengthened.",2016 Jun 13,"['Wang, Zhengting', 'Chen, Yongdi', 'Cai, Gaofeng', 'Jiang, Zhenggang', 'Liu, Kui', 'Chen, Bin', 'Jiang, Jianmin', 'Gu, Hua']",Int J Environ Res Public Health,,,True
97472ef04ad420815a0fa19076162835fad47af4,PMC,Acquisition of tumorigenic potential and enhancement of angiogenesis in pulmonary stem/progenitor cells through Oct-4 hyperexpression,http://dx.doi.org/10.18632/oncotarget.7285,PMC4924688,26871601,CC BY,"Cancer stem cells, also known as cancer initiating cells (CICs), are considered to be responsible for tumor growth and chemoresistance. Different hypotheses have been proposed to explain the origin of CICs, including mutations in adult stem/progenitor cells or the acquisition of stem-like characteristics in differentiated cells; however, studies have yielded conflicting identification for CICs and have little information for the origin to generate CICs. Part of the difficulty in identifying CICs may stem from the fact that the CICs studied have been largely derived from cancer cell lines or well-developed tumors. In previous studies, we have reported the enrichment of mouse pulmonary stem/progenitor cells (mPSCs) by using serum-free primary selection culture followed by FACS isolation using the coxsackievirus/adenovirus receptor (CAR) as the positive selection marker. Here, we demonstrated that overexpression of the pluripotent transcription factor Oct-4 is sufficient to induce CAR(+)/mPSCs transformation, which we name CAR(+)/mPSCs(Oct-4_hi). These transformed cells possess cancer initiating and chemoresistance potential, as well as exhibiting remarkable expression of certain proangiogenic factors, including angiopoietins (ANGs) and VEGF, and enhanced angiogenic potential. Moreover, CAR(+)/mPSCs(Oct-4_hi) actively participated in tumor blood vessel formation and triggered a novel angiogenic mechanism, the angiopoietins/Tie2 signaling pathway. These study provide critical evidence supporting the possible origin to generate CICs, and help elucidate the pathways responsible for CICs-mediated blood vessel formation.",2016 Feb 9,"['Gu, Sing-Yi', 'Ho, Choa-Chi', 'Huang, Yung-Kang', 'Chen, Huei-Wen', 'Wang, Yu-Chi', 'Kuo, Chia-Yu', 'Teng, Shu-Chun', 'Fu, Wen-Mei', 'Yang, Pan-Chyr', 'Wu, Cheng-Wen', 'Peng, Fu-Chuo', 'Ling, Thai-Yen']",Oncotarget,,,True
40cc2ba8d307f9dc0d11f4c57f2f22ff8c442057,PMC,Acquisition of tumorigenic potential and enhancement of angiogenesis in pulmonary stem/progenitor cells through Oct-4 hyperexpression,http://dx.doi.org/10.18632/oncotarget.7285,PMC4924688,26871601,CC BY,"Cancer stem cells, also known as cancer initiating cells (CICs), are considered to be responsible for tumor growth and chemoresistance. Different hypotheses have been proposed to explain the origin of CICs, including mutations in adult stem/progenitor cells or the acquisition of stem-like characteristics in differentiated cells; however, studies have yielded conflicting identification for CICs and have little information for the origin to generate CICs. Part of the difficulty in identifying CICs may stem from the fact that the CICs studied have been largely derived from cancer cell lines or well-developed tumors. In previous studies, we have reported the enrichment of mouse pulmonary stem/progenitor cells (mPSCs) by using serum-free primary selection culture followed by FACS isolation using the coxsackievirus/adenovirus receptor (CAR) as the positive selection marker. Here, we demonstrated that overexpression of the pluripotent transcription factor Oct-4 is sufficient to induce CAR(+)/mPSCs transformation, which we name CAR(+)/mPSCs(Oct-4_hi). These transformed cells possess cancer initiating and chemoresistance potential, as well as exhibiting remarkable expression of certain proangiogenic factors, including angiopoietins (ANGs) and VEGF, and enhanced angiogenic potential. Moreover, CAR(+)/mPSCs(Oct-4_hi) actively participated in tumor blood vessel formation and triggered a novel angiogenic mechanism, the angiopoietins/Tie2 signaling pathway. These study provide critical evidence supporting the possible origin to generate CICs, and help elucidate the pathways responsible for CICs-mediated blood vessel formation.",2016 Feb 9,"['Gu, Sing-Yi', 'Ho, Choa-Chi', 'Huang, Yung-Kang', 'Chen, Huei-Wen', 'Wang, Yu-Chi', 'Kuo, Chia-Yu', 'Teng, Shu-Chun', 'Fu, Wen-Mei', 'Yang, Pan-Chyr', 'Wu, Cheng-Wen', 'Peng, Fu-Chuo', 'Ling, Thai-Yen']",Oncotarget,,,False
4ee51bb838b0cdc2e59317a4b837f2997795b665,PMC,Hospitalization Risk Due to Respiratory Illness Associated with Genetic Variation at IFITM3 in Patients with Influenza A(H1N1)pdm09 Infection: A Case-Control Study,http://dx.doi.org/10.1371/journal.pone.0158181,PMC4924831,27351739,CC BY,"BACKGROUND: Recent studies suggest an association between the Interferon Inducible Transmembrane 3 (IFITM3) rs12252 variant and the course of influenza infection. However, it is not clear whether the reported association relates to influenza infection severity. The aim of this study was to estimate the hospitalization risk associated with this variant in Influenza Like Illness (ILI) patients during the H1N1 pandemic influenza. METHODS: A case-control genetic association study was performed, using nasopharyngeal/oropharyngeal swabs collected during the H1N1 pandemic influenza. Laboratory diagnosis of influenza infection was performed by RT-PCR, the IFITM3 rs12252 was genotyped by RFLP and tested for association with hospitalization. Conditional logistic regression was performed to calculate the confounder-adjusted odds ratio of hospitalization associated with IFITM3 rs12252. RESULTS: We selected 312 ILI cases and 624 matched non-hospitalized controls. Within ILI Influenza A(H1N1)pdm09 positive patients, no statistical significant association was found between the variant and the hospitalization risk (Adjusted OR: 0.73 (95%CI: 0.33–1.50)). Regarding ILI Influenza A(H1N1)pdm09 negative patients, CT/CC genotype carriers had a higher risk of being hospitalized than patients with TT genotype (Adjusted OR: 2.54 (95%CI: 1.54–4.19)). CONCLUSIONS: The IFITM3 rs12252 variant was associated with respiratory infection hospitalization but not specifically in patients infected with Influenza A(H1N1)pdm09.",2016 Jun 28,"['Gaio, Vânia', 'Nunes, Baltazar', 'Pechirra, Pedro', 'Conde, Patrícia', 'Guiomar, Raquel', 'Dias, Carlos Matias', 'Barreto, Marta']",PLoS One,,,True
f2f9088055600d4160e36db5cb6ea000916390a3,PMC,A Global Champion for Health—WHO’s Next?,http://dx.doi.org/10.1371/journal.pmed.1002059,PMC4924837,27351843,CC BY,"In this month’s editorial, the PLOS Medicine Editors propose ideal qualities for the World Health Organization's next Director General, for whom the selection process is now underway.",2016 Jun 28,,PLoS Med,,,True
d29ac40afbb28f3dff1d4923aae6c01299399334,PMC,A Tale of Two RNAs during Viral Infection: How Viruses Antagonize mRNAs and Small Non-Coding RNAs in The Host Cell,http://dx.doi.org/10.3390/v8060154,PMC4926174,27271653,CC BY,"Viral infection initiates an array of changes in host gene expression. Many viruses dampen host protein expression and attempt to evade the host anti-viral defense machinery. Host gene expression is suppressed at several stages of host messenger RNA (mRNA) formation including selective degradation of translationally competent messenger RNAs. Besides mRNAs, host cells also express a variety of noncoding RNAs, including small RNAs, that may also be subject to inhibition upon viral infection. In this review we focused on different ways viruses antagonize coding and noncoding RNAs in the host cell to its advantage.",2016 Jun 2,"['Herbert, Kristina M.', 'Nag, Anita']",Viruses,,,True
2ca39f3627583a75a4cd19f770b697714a89b686,PMC,Endoplasmic Reticulum: The Favorite Intracellular Niche for Viral Replication and Assembly,http://dx.doi.org/10.3390/v8060160,PMC4926180,27338443,CC BY,"The endoplasmic reticulum (ER) is the largest intracellular organelle. It forms a complex network of continuous sheets and tubules, extending from the nuclear envelope (NE) to the plasma membrane. This network is frequently perturbed by positive-strand RNA viruses utilizing the ER to create membranous replication factories (RFs), where amplification of their genomes occurs. In addition, many enveloped viruses assemble progeny virions in association with ER membranes, and viruses replicating in the nucleus need to overcome the NE barrier, requiring transient changes of the NE morphology. This review first summarizes some key aspects of ER morphology and then focuses on the exploitation of the ER by viruses for the sake of promoting the different steps of their replication cycles.",2016 Jun 7,"['Romero-Brey, Inés', 'Bartenschlager, Ralf']",Viruses,,,True
441656e0f7eea90edc2e3cb7e72d362b55e97ce3,PMC,Phleboviruses and the Type I Interferon Response,http://dx.doi.org/10.3390/v8060174,PMC4926194,27338447,CC BY,"The genus Phlebovirus of the family Bunyaviridae contains a number of emerging virus species which pose a threat to both human and animal health. Most prominent members include Rift Valley fever virus (RVFV), sandfly fever Naples virus (SFNV), sandfly fever Sicilian virus (SFSV), Toscana virus (TOSV), Punta Toro virus (PTV), and the two new members severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV). The nonstructural protein NSs is well established as the main phleboviral virulence factor in the mammalian host. NSs acts as antagonist of the antiviral type I interferon (IFN) system. Recent progress in the elucidation of the molecular functions of a growing list of NSs proteins highlights the astonishing variety of strategies employed by phleboviruses to evade the IFN system.",2016 Jun 22,"['Wuerth, Jennifer Deborah', 'Weber, Friedemann']",Viruses,,,True
09242b23825a9c7e09660df99494b673e5abea3e,PMC,Membrane protein assembly: two cytoplasmic phosphorylated serine sites of Vpu from HIV-1 affect oligomerization,http://dx.doi.org/10.1038/srep28866,PMC4926278,27353136,CC BY,"Viral protein U (Vpu) encoded by human immunodeficiency virus type 1 (HIV-1) is a short integral membrane protein which is known to self-assemble within the lipid membrane and associate with host factors during the HIV-1 infectivity cycle. In this study, full-length Vpu (M group) from clone NL4-3 was over-expressed in human cells and purified in an oligomeric state. Various single and double mutations were constructed on its phosphorylation sites to mimic different degrees of phosphorylation. Size exclusion chromatography of wild-type Vpu and mutants indicated that the smallest assembly unit of Vpu was a dimer and over time Vpu formed higher oligomers. The rate of oligomerization increased when (i) the degree of phosphorylation at serines 52 and 56 was decreased and (ii) when the ionic strength was increased indicating that the cytoplasmic domain of Vpu affects oligomerization. Coarse-grained molecular dynamic simulations with models of wild-type and mutant Vpu in a hydrated lipid bilayer supported the experimental data in demonstrating that, in addition to a previously known role in downregulation of host factors, the phosphorylation sites of Vpu also modulate oligomerization.",2016 Jun 29,"['Chen, Chin-Pei', 'Lin, Meng-Han', 'Chan, Ya-Ting', 'Chen, Li-Chyong', 'Ma, Che', 'Fischer, Wolfgang B.']",Sci Rep,,,True
b18ff7b65ed56a87c0c0de1ee312b8a0ddb51e4c,PMC,Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice,http://dx.doi.org/10.1038/srep28950,PMC4928056,27358191,CC BY,"Small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) has been implicated as a co-chaperone and regulator of androgen and growth hormone receptor (AR, GHR) signalling. We investigated the functional consequences of partial and full Sgta ablation in vivo using Cre-lox Sgta-null mice. Sgta(+/−) breeders generated viable Sgta(−/−) offspring, but at less than Mendelian expectancy. Sgta(−/−) breeders were subfertile with small litters and higher neonatal death (P < 0.02). Body size was significantly and proportionately smaller in male and female Sgta(−/−) (vs WT, Sgta(+/−) P < 0.001) from d19. Serum IGF-1 levels were genotype- and sex-dependent. Food intake, muscle and bone mass and adiposity were unchanged in Sgta(−/−). Vital and sex organs had normal relative weight, morphology and histology, although certain androgen-sensitive measures such as penis and preputial size, and testis descent, were greater in Sgta(−/−). Expression of AR and its targets remained largely unchanged, although AR localisation was genotype- and tissue-dependent. Generally expression of other TPR-containing proteins was unchanged. In conclusion, this thorough investigation of SGTA-null mutation reports a mild phenotype of reduced body size. The model’s full potential likely will be realised by genetic crosses with other models to interrogate the role of SGTA in the many diseases in which it has been implicated.",2016 Jun 30,"['Philp, Lisa K.', 'Day, Tanya K.', 'Butler, Miriam S.', 'Laven-Law, Geraldine', 'Jindal, Shalini', 'Hickey, Theresa E.', 'Scher, Howard I.', 'Butler, Lisa M.', 'Tilley, Wayne D.']",Sci Rep,,,True
9d465783b4ea9f810aa9608632a594d3e80dca03,PMC,Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice,http://dx.doi.org/10.1038/srep28950,PMC4928056,27358191,CC BY,"Small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) has been implicated as a co-chaperone and regulator of androgen and growth hormone receptor (AR, GHR) signalling. We investigated the functional consequences of partial and full Sgta ablation in vivo using Cre-lox Sgta-null mice. Sgta(+/−) breeders generated viable Sgta(−/−) offspring, but at less than Mendelian expectancy. Sgta(−/−) breeders were subfertile with small litters and higher neonatal death (P < 0.02). Body size was significantly and proportionately smaller in male and female Sgta(−/−) (vs WT, Sgta(+/−) P < 0.001) from d19. Serum IGF-1 levels were genotype- and sex-dependent. Food intake, muscle and bone mass and adiposity were unchanged in Sgta(−/−). Vital and sex organs had normal relative weight, morphology and histology, although certain androgen-sensitive measures such as penis and preputial size, and testis descent, were greater in Sgta(−/−). Expression of AR and its targets remained largely unchanged, although AR localisation was genotype- and tissue-dependent. Generally expression of other TPR-containing proteins was unchanged. In conclusion, this thorough investigation of SGTA-null mutation reports a mild phenotype of reduced body size. The model’s full potential likely will be realised by genetic crosses with other models to interrogate the role of SGTA in the many diseases in which it has been implicated.",2016 Jun 30,"['Philp, Lisa K.', 'Day, Tanya K.', 'Butler, Miriam S.', 'Laven-Law, Geraldine', 'Jindal, Shalini', 'Hickey, Theresa E.', 'Scher, Howard I.', 'Butler, Lisa M.', 'Tilley, Wayne D.']",Sci Rep,,,False
1dfc1d885254d7df5f71844b7de87fb6c9539662,PMC,Isolation and characterization of porcine epidemic diarrhea virus associated with the 2014 disease outbreak in Mexico: case report,http://dx.doi.org/10.1186/s12917-016-0763-z,PMC4928271,27357720,CC BY,"BACKGROUND: Interest in porcine epidemic diarrhea has grown since the 2013 outbreak in the United States caused major losses, with mortality rates up to 100 % in suckling piglets. In Mexico, an outbreak of porcine epidemic diarrhea, characterized by 100 % mortality in piglets, began in March 2014 in the State of Mexico. METHODS: The aim of this study was to confirm and identify porcine epidemic diarrhea virus (PEDV) in samples from piglets with suggestive clinical signs using virological, histological, and molecular techniques. Necropsy was performed on 13 piglets from two litters with initial and advanced clinical signs. Suggestive lesions of acute infection with PEDV were detected in histological sections of the small and large bowels; specifically, multiple virus particles with visible crown-shaped projections were observed using electron microscopy and negative staining. Viral isolation was performed in Vero cells with trypsin. Infection was monitored by observation of cytopathic effect, and titration was determined by TCID(50)/ml. The presence of the PEDV in cultures and clinical samples was confirmed by RT-PCR amplification and sequencing of a 651-bp segment of the S glycoprotein gene, as well as a 681-bp matrix protein gene. RESULTS: The nucleotide sequence analysis of the Mexican isolates showed marked homology to viruses that circulated in 2013 in Colorado, USA. CONCLUSIONS: In this paper we confirm the isolation and characterization of PEDV from animals with early and advanced clinical signs.",2016 Jun 29,"['Trujillo-Ortega, María Elena', 'Beltrán-Figueroa, Rolando', 'García-Hernández, Montserrat Elemi', 'Juárez-Ramírez, Mireya', 'Sotomayor-González, Alicia', 'Hernández-Villegas, Erika N.', 'Becerra-Hernández, José F.', 'Sarmiento-Silva, Rosa Elena']",BMC Vet Res,,,True
c760ba658ba0d10b96cf738e04f83f22bd15f3a3,PMC,Evidence of Aujeszky’s disease in wild boar in Serbia,http://dx.doi.org/10.1186/s12917-016-0758-9,PMC4928280,27357597,CC BY,"BACKGROUND: Aujeszky’s disease is a viral disease of suids caused by Suid Herpesvirus 1. The disease has worldwide distribution with significant economic impact. In Serbia, there is neither an Aujeszky’s disease eradication nor national vaccination programme of domestic pigs. Since clinical symptoms of Aujeszky’s disease are not specific, it is important to establish a link between clinical signs and presence of ADV active infection in wild boars. The aim of this study was to investigate the possibility of active infection within wild boar showing signs of ADV and also to examine relationship between isolates from domestic pigs and wild boar. Having in mind that virus has not been previously isolated from wild boars in Serbia, we report the first isolation of Suid Herpesvirus 1 from this species in Serbia. RESULTS: Tissue and serum samples from 40 wild boars from eastern Serbia were examined for evidence of Aujeszky’s disease (AD). Suid Herpesvirus 1 (SHV1), the cause of AD was isolated on PK15 cell line from three tissue samples, inducing cytopathic effect (CPE) with syncytia forming, and viral genome was detected by polymerase chain reaction (PCR) in eight samples. Genetic analysis of us4, us9 and ul49.5 partial sequences showed high homology between ADV isolates from wild boars and between isolates from wild boars and domestic animals. Neutralizing antibodies were not detected by virus neutralisation test (VNT) in sera from four out of eight PCR positive wild boars suggesting recent infection in those animals. CONCLUSIONS: This is the first demonstration of Aujeszky’s disease virus (ADV) in the wild boar population in Serbia although seroconversion has been detected previously.",2016 Jun 30,"['Milicevic, V.', 'Radojicic, S.', 'Valcic, M.', 'Ivovic, V.', 'Radosavljevic, V.']",BMC Vet Res,,,True
78ef6e101522626b8c7c7621ec50146ab57cf488,PMC,Inducible Bronchus-Associated Lymphoid Tissue: Taming Inflammation in the Lung,http://dx.doi.org/10.3389/fimmu.2016.00258,PMC4928648,27446088,CC BY,"Following pulmonary inflammation, leukocytes that infiltrate the lung often assemble into structures known as inducible Bronchus-Associated Lymphoid Tissue (iBALT). Like conventional lymphoid organs, areas of iBALT have segregated B and T cell areas, specialized stromal cells, high endothelial venules, and lymphatic vessels. After inflammation is resolved, iBALT is maintained for months, independently of inflammation. Once iBALT is formed, it participates in immune responses to pulmonary antigens, including those that are unrelated to the iBALT-initiating antigen, and often alters the clinical course of disease. However, the mechanisms that govern immune responses in iBALT and determine how iBALT impacts local and systemic immunity are poorly understood. Here, we review our current understanding of iBALT formation and discuss how iBALT participates in pulmonary immunity.",2016 Jun 30,"['Hwang, Ji Young', 'Randall, Troy D.', 'Silva-Sanchez, Aaron']",Front Immunol,,,True
9d8252afd663371d83c2e28943f2df1bec3f4780,PMC,Dissecting Virus Infectious Cycles by Cryo-Electron Microscopy,http://dx.doi.org/10.1371/journal.ppat.1005625,PMC4928862,27362353,CC BY,,2016 Jun 30,"['Lee, Kelly K.', 'Gui, Long']",PLoS Pathog,,,True
8ad6fe3d0031f1dffb84dec640ac0bb7c5ba84fb,PMC,Alzheimer’s disease Advax(CpG)- adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules,http://dx.doi.org/10.1038/srep28912,PMC4929459,27363809,CC BY,"Although β-amyloid (Aβ) may be the primary driver of Alzheimer’s disease (AD) pathology, accumulation of pathological tau correlates with dementia in AD patients. Thus, the prevention/inhibition of AD may require vaccine/s targeting Aβ and tau simultaneously or sequentially. Since high antibody titers are required for AD vaccine efficacy, we have decided to generate vaccines, targeting Aβ (AV-1959R), Tau (AV-1980R) or Aβ/tau (AV-1953R) B cell epitopes, based on immunogenic MultiTEP platform and evaluate the immunogenicity of these vaccines formulated with Advax(CpG), delta inulin, Alhydrogel(®), Montanide-ISA51, Montanide-ISA720, MPLA-SM pharmaceutical grade adjuvants. Formulation of AV-1959R in Advax(CpG) induced the highest cellular and humoral immune responses in mice. The dual-epitope vaccine, AV-1953R, or the combination of AV-1959R and AV-1980R vaccines formulated with Advax(CpG) induced robust antibody responses against various forms of both, Aβ and tau pathological molecules. While anti-Aβ antibody titers after AV-1953R immunization were similar to that in mice vaccinated with AV-1959R or AV-1959R/AV-1980R combination, anti-tau titers were significantly lower after AV-1953R injection when compared to the AV-1980R or AV-1959R/AV-1980R. In silico 3D-modeling provided insight into the differences in immunogenicity of these vaccine constructs. In sum, AV-1959R and AV-1980R formulated with Advax(CpG) adjuvant were identified as promising immunogenic vaccines for ongoing pre-clinical assessment and future human clinical trials.",2016 Jul 1,"['Davtyan, Hayk', 'Zagorski, Karen', 'Rajapaksha, Harinda', 'Hovakimyan, Armine', 'Davtyan, Arpine', 'Petrushina, Irina', 'Kazarian, Konstantin', 'Cribbs, David H.', 'Petrovsky, Nikolai', 'Agadjanyan, Michael G.', 'Ghochikyan, Anahit']",Sci Rep,,,True
9933e9bd314173e10397a75c88d68c482a122289,PMC,Alzheimer’s disease Advax(CpG)- adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules,http://dx.doi.org/10.1038/srep28912,PMC4929459,27363809,CC BY,"Although β-amyloid (Aβ) may be the primary driver of Alzheimer’s disease (AD) pathology, accumulation of pathological tau correlates with dementia in AD patients. Thus, the prevention/inhibition of AD may require vaccine/s targeting Aβ and tau simultaneously or sequentially. Since high antibody titers are required for AD vaccine efficacy, we have decided to generate vaccines, targeting Aβ (AV-1959R), Tau (AV-1980R) or Aβ/tau (AV-1953R) B cell epitopes, based on immunogenic MultiTEP platform and evaluate the immunogenicity of these vaccines formulated with Advax(CpG), delta inulin, Alhydrogel(®), Montanide-ISA51, Montanide-ISA720, MPLA-SM pharmaceutical grade adjuvants. Formulation of AV-1959R in Advax(CpG) induced the highest cellular and humoral immune responses in mice. The dual-epitope vaccine, AV-1953R, or the combination of AV-1959R and AV-1980R vaccines formulated with Advax(CpG) induced robust antibody responses against various forms of both, Aβ and tau pathological molecules. While anti-Aβ antibody titers after AV-1953R immunization were similar to that in mice vaccinated with AV-1959R or AV-1959R/AV-1980R combination, anti-tau titers were significantly lower after AV-1953R injection when compared to the AV-1980R or AV-1959R/AV-1980R. In silico 3D-modeling provided insight into the differences in immunogenicity of these vaccine constructs. In sum, AV-1959R and AV-1980R formulated with Advax(CpG) adjuvant were identified as promising immunogenic vaccines for ongoing pre-clinical assessment and future human clinical trials.",2016 Jul 1,"['Davtyan, Hayk', 'Zagorski, Karen', 'Rajapaksha, Harinda', 'Hovakimyan, Armine', 'Davtyan, Arpine', 'Petrushina, Irina', 'Kazarian, Konstantin', 'Cribbs, David H.', 'Petrovsky, Nikolai', 'Agadjanyan, Michael G.', 'Ghochikyan, Anahit']",Sci Rep,,,False
6907124581ac28f6712e3676396cfc4a3b8a9502,PMC,Accelerating skin wound healing by M-CSF through generating SSEA-1 and -3 stem cells in the injured sites,http://dx.doi.org/10.1038/srep28979,PMC4929493,27363517,CC BY,"Wound healing is a complicated process requiring the collaborative efforts of different cell lineages. Our recent studies have found that one subset of hematopoietic cells can be induced to dedifferentiate into multipotent stem cells by means of a proliferating fibroblast releasable factor, M-CSF. Understanding the importance of stem cells on skin wound healing, here we evaluate the biological significance of M-CSF on skin wound healing. In an in vivo mouse skin excisional wound model, we found that SSEA-positive stem cells were present in wounded but not normal skin. After isolating skin cells from either normal or wounded skin by collagenase digestion, and analyzing the SSEA-1 positive cells by flow cytometry, we found a significant increase in the number of SSEA-1 positive cells in wounded skin. Topical application of M-CSF in skin wounds accelerated healing remarkably, while application of M-CSF-neutralizing antibody slowed wound healing. Furthermore, injection of EGFP-labeled hematopoietic cell-derived stem cells generated from M-CSF treated splenocytes resulted in EGFP-labeled cells being enriched in the skin wound site and further differentiated into functional organ-specific cells. Together, these data demonstrated that M-CSF makes a significant contribution to the healing process by inducing hematopoietic cell dedifferentiation into stem cells.",2016 Jul 1,"['Li, Yunyuan', 'Jalili, Reza Baradar', 'Ghahary, Aziz']",Sci Rep,,,True
2c35971bf39265b7ccb2721d0079e0a4fd019ad1,PMC,Accelerating skin wound healing by M-CSF through generating SSEA-1 and -3 stem cells in the injured sites,http://dx.doi.org/10.1038/srep28979,PMC4929493,27363517,CC BY,"Wound healing is a complicated process requiring the collaborative efforts of different cell lineages. Our recent studies have found that one subset of hematopoietic cells can be induced to dedifferentiate into multipotent stem cells by means of a proliferating fibroblast releasable factor, M-CSF. Understanding the importance of stem cells on skin wound healing, here we evaluate the biological significance of M-CSF on skin wound healing. In an in vivo mouse skin excisional wound model, we found that SSEA-positive stem cells were present in wounded but not normal skin. After isolating skin cells from either normal or wounded skin by collagenase digestion, and analyzing the SSEA-1 positive cells by flow cytometry, we found a significant increase in the number of SSEA-1 positive cells in wounded skin. Topical application of M-CSF in skin wounds accelerated healing remarkably, while application of M-CSF-neutralizing antibody slowed wound healing. Furthermore, injection of EGFP-labeled hematopoietic cell-derived stem cells generated from M-CSF treated splenocytes resulted in EGFP-labeled cells being enriched in the skin wound site and further differentiated into functional organ-specific cells. Together, these data demonstrated that M-CSF makes a significant contribution to the healing process by inducing hematopoietic cell dedifferentiation into stem cells.",2016 Jul 1,"['Li, Yunyuan', 'Jalili, Reza Baradar', 'Ghahary, Aziz']",Sci Rep,,,False
b293192e82a70515cb199bca870a9fe2ca9b081d,PMC,Nasopharyngeal microbiota composition of children is related to the frequency of upper respiratory infection and acute sinusitis,http://dx.doi.org/10.1186/s40168-016-0179-9,PMC4929776,27364497,CC BY,"BACKGROUND: Upper respiratory infections (URI) and their complications are a major healthcare burden for pediatric populations. Although the microbiology of the nasopharynx is an important determinant of the complications of URI, little is known of the nasopharyngeal (NP) microbiota of children, the factors that affect its composition, and its precise relationship with URI. RESULTS: Healthy children (n = 47) aged 49–84 months from a prospective cohort study based in Wisconsin, USA, were examined. Demographic and clinical data and NP swab samples were obtained from participants upon entry to the study. All NP samples were profiled for bacterial microbiota using a phylogenetic microarray, and these data were related to demographic characteristics and upper respiratory health outcomes. The composition of the NP bacterial community of children was significantly related prior to the history of acute sinusitis (R(2) = 0.070, P < 0.009). History of acute sinusitis was associated with significant depletion in relative abundance of taxa including Faecalibacterium prausnitzii and Akkermansia spp. and enrichment of Moraxella nonliquefaciens. Enrichment of M. nonliquefaciens was also a characteristic of baseline NP samples of children who subsequently developed acute sinusitis over the 1-year study period. Time to develop URI was significantly positively correlated with NP diversity, and children who experienced more frequent URIs exhibited significantly diminished NP microbiota diversity (P ≤ 0.05). CONCLUSIONS: These preliminary data suggest that previous history of acute sinusitis influences the composition of the NP microbiota, characterized by a depletion in relative abundance of specific taxa. Diminished diversity was associated with more frequent URIs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40168-016-0179-9) contains supplementary material, which is available to authorized users.",2016 Jul 1,"['Santee, Clark A.', 'Nagalingam, Nabeetha A.', 'Faruqi, Ali A.', 'DeMuri, Gregory P.', 'Gern, James E.', 'Wald, Ellen R.', 'Lynch, Susan V.']",Microbiome,,,True
0ddcfc9bedfb0a87a7221dd2448bd41d3ba9cc51,PMC,How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?,http://dx.doi.org/10.1371/journal.pone.0158237,PMC4930163,27367230,CC BY,"Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements.",2016 Jul 1,"['Vegvari, Carolin', 'Hadjichrysanthou, Christoforos', 'Cauët, Emilie', 'Lawrence, Emma', 'Cori, Anne', 'de Wolf, Frank', 'Anderson, Roy M.']",PLoS One,,,True
73fcc68f1fe5bf9cae21d939f459968ebed64411,PMC,Hepatitis C Virus Core Protein Promotes miR-122 Destabilization by Inhibiting GLD-2,http://dx.doi.org/10.1371/journal.ppat.1005714,PMC4930175,27366906,CC BY,"The liver-specific microRNA miR-122, which has essential roles in liver development and metabolism, is a key proviral factor for hepatitis C virus (HCV). Despite its crucial role in the liver and HCV life cycle, little is known about the molecular mechanism of miR-122 expression regulation by HCV infection. Here, we show that the HCV core protein downregulates the abundance of miR-122 by promoting its destabilization via the inhibition of GLD-2, a non-canonical cytoplasmic poly(A) polymerase. The decrease in miR-122 expression resulted in the dysregulation of the known functions of miR-122, including its proviral activity for HCV. By high-throughput sequencing of small RNAs from human liver biopsies, we found that the 22-nucleotide (nt) prototype miR-122 is modified at its 3′ end by 3′-terminal non-templated and templated nucleotide additions. Remarkably, the proportion of miR-122 isomers bearing a single nucleotide tail of any ribonucleotide decreased in liver specimens from patients with HCV. We found that these single-nucleotide-tailed miR-122 isomers display increased miRNA activity and stability over the 22-nt prototype miR-122 and that the 3′-terminal extension is catalyzed by the unique terminal nucleotidyl transferase activity of GLD-2, which is capable of adding any single ribonucleotide without preference of adenylate to the miR-122 3′ end. The HCV core protein specifically inhibited GLD-2, and its interaction with GLD-2 in the cytoplasm was found to be responsible for miR-122 downregulation. Collectively, our results provide new insights into the regulatory role of the HCV core protein in controlling viral RNA abundance and miR-122 functions through miR-122 stability modulation.",2016 Jul 1,"['Kim, Geon-Woo', 'Lee, Seung-Hoon', 'Cho, Hee', 'Kim, Minwoo', 'Shin, Eui-Cheol', 'Oh, Jong-Won']",PLoS Pathog,,,True
e0111854ce52152339b685712b1a2843e3f1b839,PMC,Nucleolin interacts with influenza A nucleoprotein and contributes to viral ribonucleoprotein complexes nuclear trafficking and efficient influenza viral replication,http://dx.doi.org/10.1038/srep29006,PMC4931502,27373907,CC BY,"Influenza viruses replicate their single-stranded RNA genomes in the nucleus of infected cells and these replicated genomes (vRNPs) are then exported from the nucleus to the cytoplasm and plasma membrane before budding. To achieve this export, influenza viruses hijack the host cell export machinery. However, the complete mechanisms underlying this hijacking remain not fully understood. We have previously shown that influenza viruses induce a marked alteration of the nucleus during the time-course of infection and notably in the nucleolar compartment. In this study, we discovered that a major nucleolar component, called nucleolin, is required for an efficient export of vRNPs and viral replication. We have notably shown that nucleolin interacts with the viral nucleoprotein (NP) that mainly constitutes vRNPs. Our results suggest that this interaction could allow vRNPs to “catch” the host cell export machinery, a necessary step for viral replication.",2016 Jul 4,"['Terrier, Olivier', 'Carron, Coralie', 'De Chassey, Benoît', 'Dubois, Julia', 'Traversier, Aurélien', 'Julien, Thomas', 'Cartet, Gaëlle', 'Proust, Anaïs', 'Hacot, Sabine', 'Ressnikoff, Denis', 'Lotteau, Vincent', 'Lina, Bruno', 'Diaz, Jean-Jacques', 'Moules, Vincent', 'Rosa-Calatrava, Manuel']",Sci Rep,,,True
47f27a1405f69dd7569f6b5d2f0f73b72fcf4c38,PMC,Nucleolin interacts with influenza A nucleoprotein and contributes to viral ribonucleoprotein complexes nuclear trafficking and efficient influenza viral replication,http://dx.doi.org/10.1038/srep29006,PMC4931502,27373907,CC BY,"Influenza viruses replicate their single-stranded RNA genomes in the nucleus of infected cells and these replicated genomes (vRNPs) are then exported from the nucleus to the cytoplasm and plasma membrane before budding. To achieve this export, influenza viruses hijack the host cell export machinery. However, the complete mechanisms underlying this hijacking remain not fully understood. We have previously shown that influenza viruses induce a marked alteration of the nucleus during the time-course of infection and notably in the nucleolar compartment. In this study, we discovered that a major nucleolar component, called nucleolin, is required for an efficient export of vRNPs and viral replication. We have notably shown that nucleolin interacts with the viral nucleoprotein (NP) that mainly constitutes vRNPs. Our results suggest that this interaction could allow vRNPs to “catch” the host cell export machinery, a necessary step for viral replication.",2016 Jul 4,"['Terrier, Olivier', 'Carron, Coralie', 'De Chassey, Benoît', 'Dubois, Julia', 'Traversier, Aurélien', 'Julien, Thomas', 'Cartet, Gaëlle', 'Proust, Anaïs', 'Hacot, Sabine', 'Ressnikoff, Denis', 'Lotteau, Vincent', 'Lina, Bruno', 'Diaz, Jean-Jacques', 'Moules, Vincent', 'Rosa-Calatrava, Manuel']",Sci Rep,,,False
9033d46664d7ded6d2cd79ddb75c2c36beab4802,PMC,Vimentin in Bacterial Infections,http://dx.doi.org/10.3390/cells5020018,PMC4931667,27096872,CC BY,"Despite well-studied bacterial strategies to target actin to subvert the host cell cytoskeleton, thus promoting bacterial survival, replication, and dissemination, relatively little is known about the bacterial interaction with other components of the host cell cytoskeleton, including intermediate filaments (IFs). IFs have not only roles in maintaining the structural integrity of the cell, but they are also involved in many cellular processes including cell adhesion, immune signaling, and autophagy, processes that are important in the context of bacterial infections. Here, we summarize the knowledge about the role of IFs in bacterial infections, focusing on the type III IF protein vimentin. Recent studies have revealed the involvement of vimentin in host cell defenses, acting as ligand for several pattern recognition receptors of the innate immune system. Two main aspects of bacteria-vimentin interactions are presented in this review: the role of vimentin in pathogen-binding on the cell surface and subsequent bacterial invasion and the interaction of cytosolic vimentin and intracellular pathogens with regards to innate immune signaling. Mechanistic insight is presented involving distinct bacterial virulence factors that target vimentin to subvert its function in order to change the host cell fate in the course of a bacterial infection.",2016 Apr 18,"['Mak, Tim N.', 'Brüggemann, Holger']",Cells,,,True
a21f8d21e09607e555468d0ed155126daaeb37cd,PMC,First isolation of West Nile virus from a dromedary camel,http://dx.doi.org/10.1038/emi.2016.53,PMC4932647,27273223,CC BY,"Although antibodies against West Nile virus (WNV) have been detected in the sera of dromedaries in the Middle East, North Africa and Spain, no WNV has been isolated or amplified from dromedary or Bactrian camels. In this study, WNV was isolated from Vero cells inoculated with both nasal swab and pooled trachea/lung samples from a dromedary calf in Dubai. Complete-genome sequencing and phylogenetic analysis using the near-whole-genome polyprotein revealed that the virus belonged to lineage 1a. There was no clustering of the present WNV with other WNVs isolated in other parts of the Middle East. Within lineage 1a, the dromedary WNV occupied a unique position, although it was most closely related to other WNVs of cluster 2. Comparative analysis revealed that the putative E protein encoded by the genome possessed the original WNV E protein glycosylation motif NYS at E154–156, which contained the N-linked glycosylation site at N-154 associated with increased WNV pathogenicity and neuroinvasiveness. In the putative NS1 protein, the A70S substitution observed in other cluster 2 WNVs and P250, which has been implicated in neuroinvasiveness, were present. In addition, the foo motif in the putative NS2A protein, which has been implicated in neuroinvasiveness, was detected. Notably, the amino-acid residues at 14 positions in the present dromedary WNV genome differed from those in most of the closely related WNV strains in cluster 2 of lineage 1a, with the majority of these differences observed in the putative E and NS5 proteins. The present study is the first to demonstrate the isolation of WNV from dromedaries. This finding expands the possible reservoirs of WNV and sources of WNV infection.",2016 Jun 8,"['Joseph, Sunitha', 'Wernery, Ulrich', 'Teng, Jade LL', 'Wernery, Renate', 'Huang, Yi', 'Patteril, Nissy AG', 'Chan, Kwok-Hung', 'Elizabeth, Shyna K', 'Fan, Rachel YY', 'Lau, Susanna KP', 'Kinne, Jörg', 'Woo, Patrick CY']",Emerg Microbes Infect,,,True
bbf555548912f929c3413cf6ee3314f9783cbb18,PMC,"An outbreak of cutaneous anthrax in Yunnan, China",http://dx.doi.org/10.1038/emi.2016.65,PMC4932653,27329849,CC BY,,2016 Jun 22,"['Huang, Ying', 'Du, Yingrong', 'Wang, Yaling', 'Wang, Ning', 'Bai, Jinsong', 'Chen, Haiyun', 'He, Hua', 'Xu, Jun', 'Wu, Yan', 'Luo, Yun', 'Li, Xiaolong', 'Liang, Guodong']",Emerg Microbes Infect,,,True
ab4c508f4a6ff84276581ce0746b4a5768728d0f,PMC,Occurrence of canine parvovirus in dogs from Henan province of China in 2009–2014,http://dx.doi.org/10.1186/s12917-016-0753-1,PMC4932751,27377264,CC BY,"BACKGROUND: There is no information concerning the genotype of Canine parvovirus (CPV) currently circulating in Henan province, China. Therefore, the aim of the present study was to provide insights into the epidemiology and molecular characterization of CPV circulating in Henan province from 2009 to 2014. RESULTS: Nineteen thousand nine hundred seven dogs from pet hospitals in the cities of Luoyang, Anyang, Jiaozuo, Sanmenxia, Xinxiang, Zhengzhou in Henan province between 2009 and 2014 were investigated. Over the 6-year period, 1169 CPV-positive cases were identified and the morbidity of CPV infection ranged from 4.16 to 8.06 %, although morbidity was not significant (P > 0.05) between 2009 and 2014. Factors associated with morbidity included sampling season, dog age, breed, vaccination status, and sex. CPV co-infection with coccidium (10.00 %), canine distemper virus (4.79 %), hookworm (2.40 %), canine coronavirus (1.11 %), roundworm (1.03 %), tapeworm (0.17 %) and Babesia spp. (0.09 %) were observed. The new CPV-2a variant was more prevalent than the new CPV-2b variant in Henan province. CPV 2c was not observed in this study. CONCLUSIONS: The epidemiology of CPV infection and identification of the circulating genotypes in Henan province, China from 2009 to 2014 determined that the new CPV-2a variant was more prevalent.",2016 Jul 4,"['Zhao, Zhanqin', 'Liu, Huisheng', 'Ding, Ke', 'Peng, Chunping', 'Xue, Qiao', 'Yu, Zuhua', 'Xue, Yun']",BMC Vet Res,,,True
c8de62f6c2fb721f1a0e80c81b70438ec75a9702,PMC,"Clean energy benefits the climate, the economy and our health",http://dx.doi.org/10.2471/BLT.16.030716,PMC4933147,27429487,CC BY,"Jeffrey D Sachs tells Fiona Fleck why investing in renewable energy is good for our health, but why poor countries need more time to make the switch.",2016 Jul 1,,Bull World Health Organ,,,False
039ca723ee32358eb70a084eaee19e1b6adc3033,PMC,"Global epidemiology of avian influenza A(H5N1) virus infection in humans, 1997 – 2015: a systematic review",http://dx.doi.org/10.1016/S1473-3099(16)00153-5,PMC4933299,27211899,CC BY,"Avian influenza viruses A(H5N1) have caused a large number of typically severe human infections since the first human case was reported in 1997. However, there is a lack of comprehensive epidemiological analysis of global human cases of H5N1 from 1997-2015. Moreover, few studies have examined in detail the changing epidemiology of human H5N1 cases in Egypt, especially given the most recent outbreaks since November 2014 which have the highest number of cases ever reported globally over a similar period. Data on individual cases were collated from different sources using a systematic approach to describe the global epidemiology of 907 human H5N1 cases between May 1997 and April 2015. The number of affected countries rose between 2003 and 2008, with expansion from East and Southeast Asia, then to West Asia and Africa. Most cases (67.2%) occurred from December to March, and the overall case fatality risk was 53.5% (483/903) which varied across geographical regions. Although the incidence in Egypt has increased dramatically since November 2014, compared to the cases beforehand there were no significant differences in the fatality risk , history of exposure to poultry, history of human case contact, and time from onset to hospitalization in the recent cases.",2016 Jul 17,"['Lai, Shengjie', 'Qin, Ying', 'Cowling, Benjamin J.', 'Ren, Xiang', 'Wardrop, Nicola A.', 'Gilbert, Marius', 'Tsang, Tim K.', 'Wu, Peng', 'Feng, Luzhao', 'Jiang, Hui', 'Peng, Zhibin', 'Zheng, Jiandong', 'Liao, Qiaohong', 'Li, Sa', 'Horby, Peter W.', 'Farrar, Jeremy J.', 'Gao, George F.', 'Tatem, Andrew J.', 'Yu, Hongjie']",Lancet Infect Dis,,,True
ab70ed497469460f2ec13fcfe51611005fab867a,PMC,Acute systemic DNA damage in youth does not impair immune defense with aging,http://dx.doi.org/10.1111/acel.12478,PMC4933672,27072188,CC BY,"Aging‐related decline in immunity is believed to be the main driver behind decreased vaccine efficacy and reduced resistance to infections in older adults. Unrepaired DNA damage is known to precipitate cellular senescence, which was hypothesized to be the underlying cause of certain age‐related phenotypes. Consistent with this, some hallmarks of immune aging were more prevalent in individuals exposed to whole‐body irradiation (WBI), which leaves no anatomical repository of undamaged hematopoietic cells. To decisively test whether and to what extent WBI in youth will leave a mark on the immune system as it ages, we exposed young male C57BL/6 mice to sublethal WBI (0.5–4 Gy), mimicking human survivor exposure during nuclear catastrophe. We followed lymphocyte homeostasis thorough the lifespan, response to vaccination, and ability to resist lethal viral challenge in the old age. None of the irradiated groups showed significant differences compared with mock‐irradiated (0 Gy) animals for the parameters measured. Even the mice that received the highest dose of sublethal WBI in youth (4 Gy) exhibited equilibrated lymphocyte homeostasis, robust T‐ and B‐cell responses to live attenuated West Nile virus (WNV) vaccine and full survival following vaccination upon lethal WNV challenge. Therefore, a single dose of nonlethal WBI in youth, resulting in widespread DNA damage and repopulation stress in hematopoietic cells, leaves no significant trace of increased immune aging in a lethal vaccine challenge model.",2016 Aug 13,"['Pugh, Jason L.', 'Foster, Sarah A.', 'Sukhina, Alona S.', 'Petravic, Janka', 'Uhrlaub, Jennifer L.', 'Padilla‐Torres, Jose', 'Hayashi, Tomonori', 'Nakachi, Kei', 'Smithey, Megan J.', 'Nikolich‐Žugich, Janko']",Aging Cell,,,True
e7976bbd13a90d95e706215c8d42c629fc7d5b4d,PMC,Acute systemic DNA damage in youth does not impair immune defense with aging,http://dx.doi.org/10.1111/acel.12478,PMC4933672,27072188,CC BY,"Aging‐related decline in immunity is believed to be the main driver behind decreased vaccine efficacy and reduced resistance to infections in older adults. Unrepaired DNA damage is known to precipitate cellular senescence, which was hypothesized to be the underlying cause of certain age‐related phenotypes. Consistent with this, some hallmarks of immune aging were more prevalent in individuals exposed to whole‐body irradiation (WBI), which leaves no anatomical repository of undamaged hematopoietic cells. To decisively test whether and to what extent WBI in youth will leave a mark on the immune system as it ages, we exposed young male C57BL/6 mice to sublethal WBI (0.5–4 Gy), mimicking human survivor exposure during nuclear catastrophe. We followed lymphocyte homeostasis thorough the lifespan, response to vaccination, and ability to resist lethal viral challenge in the old age. None of the irradiated groups showed significant differences compared with mock‐irradiated (0 Gy) animals for the parameters measured. Even the mice that received the highest dose of sublethal WBI in youth (4 Gy) exhibited equilibrated lymphocyte homeostasis, robust T‐ and B‐cell responses to live attenuated West Nile virus (WNV) vaccine and full survival following vaccination upon lethal WNV challenge. Therefore, a single dose of nonlethal WBI in youth, resulting in widespread DNA damage and repopulation stress in hematopoietic cells, leaves no significant trace of increased immune aging in a lethal vaccine challenge model.",2016 Aug 13,"['Pugh, Jason L.', 'Foster, Sarah A.', 'Sukhina, Alona S.', 'Petravic, Janka', 'Uhrlaub, Jennifer L.', 'Padilla‐Torres, Jose', 'Hayashi, Tomonori', 'Nakachi, Kei', 'Smithey, Megan J.', 'Nikolich‐Žugich, Janko']",Aging Cell,,,False
b8a55c284d17093b3d9c033f5c74633f47aaabe3,PMC,"The IRIDICA BAC BSI Assay: Rapid, Sensitive and Culture-Independent Identification of Bacteria and Candida in Blood",http://dx.doi.org/10.1371/journal.pone.0158186,PMC4934770,27384540,CC BY,"Bloodstream infection (BSI) and sepsis are rising in incidence throughout the developed world. The spread of multi-drug resistant organisms presents increasing challenges to treatment. Surviving BSI is dependent on rapid and accurate identification of causal organisms, and timely application of appropriate antibiotics. Current culture-based methods used to detect and identify agents of BSI are often too slow to impact early therapy and may fail to detect relevant organisms in many positive cases. Existing methods for direct molecular detection of microbial DNA in blood are limited in either sensitivity (likely the result of small sample volumes) or in breadth of coverage, often because the PCR primers and probes used target only a few specific pathogens. There is a clear unmet need for a sensitive molecular assay capable of identifying the diverse bacteria and yeast associated with BSI directly from uncultured whole blood samples. We have developed a method of extracting DNA from larger volumes of whole blood (5 ml per sample), amplifying multiple widely conserved bacterial and fungal genes using a mismatch- and background-tolerant PCR chemistry, and identifying hundreds of diverse organisms from the amplified fragments on the basis of species-specific genetic signatures using electrospray ionization mass spectrometry (PCR/ESI-MS). We describe the analytical characteristics of the IRIDICA BAC BSI Assay and compare its pre-clinical performance to current standard-of-care methods in a collection of prospectively collected blood specimens from patients with symptoms of sepsis. The assay generated matching results in 80% of culture-positive cases (86% when common contaminants were excluded from the analysis), and twice the total number of positive detections. The described method is capable of providing organism identifications directly from uncultured blood in less than 8 hours. Disclaimer: The IRIDICA BAC BSI Assay is not available in the United States.",2016 Jul 6,"['Metzgar, David', 'Frinder, Mark W.', 'Rothman, Richard E.', 'Peterson, Stephen', 'Carroll, Karen C.', 'Zhang, Sean X.', 'Avornu, Gideon D.', 'Rounds, Megan A.', 'Carolan, Heather E.', 'Toleno, Donna M.', 'Moore, David', 'Hall, Thomas A.', 'Massire, Christian', 'Richmond, Gregory S.', 'Gutierrez, Jose R.', 'Sampath, Rangarajan', 'Ecker, David J.', 'Blyn, Lawrence B.']",PLoS One,,,True
7146a5eb303bef6ef7c4bc2588a0305fc7b58cd3,PMC,Illuminating the Sites of Enterovirus Replication in Living Cells by Using a Split-GFP-Tagged Viral Protein,http://dx.doi.org/10.1128/mSphere.00104-16,PMC4935779,27390781,CC BY,"Like all other positive-strand RNA viruses, enteroviruses generate new organelles (replication organelles [ROs]) with a unique protein and lipid composition on which they multiply their viral genome. Suitable tools for live-cell imaging of enterovirus ROs are currently unavailable, as recombinant enteroviruses that carry genes that encode RO-anchored viral proteins tagged with fluorescent reporters have not been reported thus far. To overcome this limitation, we used a split green fluorescent protein (split-GFP) system, comprising a large fragment [strands 1 to 10; GFP(S1-10)] and a small fragment [strand 11; GFP(S11)] of only 16 residues. The GFP(S11) (GFP with S11 fragment) fragment was inserted into the 3A protein of the enterovirus coxsackievirus B3 (CVB3), while the large fragment was supplied by transient or stable expression in cells. The introduction of GFP(S11) did not affect the known functions of 3A when expressed in isolation. Using correlative light electron microscopy (CLEM), we showed that GFP fluorescence was detected at ROs, whose morphologies are essentially identical to those previously observed for wild-type CVB3, indicating that GFP(S11)-tagged 3A proteins assemble with GFP(S1-10) to form GFP for illumination of bona fide ROs. It is well established that enterovirus infection leads to Golgi disintegration. Through live-cell imaging of infected cells expressing an mCherry-tagged Golgi marker, we monitored RO development and revealed the dynamics of Golgi disassembly in real time. Having demonstrated the suitability of this virus for imaging ROs, we constructed a CVB3 encoding GFP(S1-10) and GFP(S11)-tagged 3A to bypass the need to express GFP(S1-10) prior to infection. These tools will have multiple applications in future studies on the origin, location, and function of enterovirus ROs. IMPORTANCE Enteroviruses induce the formation of membranous structures (replication organelles [ROs]) with a unique protein and lipid composition specialized for genome replication. Electron microscopy has revealed the morphology of enterovirus ROs, and immunofluorescence studies have been conducted to investigate their origin and formation. Yet, immunofluorescence analysis of fixed cells results in a rather static view of RO formation, and the results may be compromised by immunolabeling artifacts. While live-cell imaging of ROs would be preferred, enteroviruses encoding a membrane-anchored viral protein fused to a large fluorescent reporter have thus far not been described. Here, we tackled this constraint by introducing a small tag from a split-GFP system into an RO-resident enterovirus protein. This new tool bridges a methodological gap by circumventing the need for immunolabeling fixed cells and allows the study of the dynamics and formation of enterovirus ROs in living cells.",2016 Jul 6,"['van der Schaar, H. M.', 'Melia, C. E.', 'van Bruggen, J. A. C.', 'Strating, J. R. P. M.', 'van Geenen, M. E. D.', 'Koster, A. J.', 'Bárcena, M.', 'van Kuppeveld, F. J. M.']",mSphere,,,True
6ff089187feaca34bce964cc052bd1fa0f016d40,PMC,Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury,http://dx.doi.org/10.1155/2016/9476020,PMC4935915,27418745,CC BY,"Spinal cord injury results in a life-disrupting series of deleterious interconnected mechanisms encompassed by the primary and secondary injury. These events are mediated by the upregulation of genes with roles in inflammation, transcription, and signaling proteins. In particular, cytokines and growth factors are signaling proteins that have important roles in the pathophysiology of SCI. The balance between the proinflammatory and anti-inflammatory effects of these molecules plays a critical role in the progression and outcome of the lesion. The excessive inflammatory Th1 and Th17 phenotypes observed after SCI tilt the scale towards a proinflammatory environment, which exacerbates the deleterious mechanisms present after the injury. These mechanisms include the disruption of the spinal cord blood barrier, edema and ion imbalance, in particular intracellular calcium and sodium concentrations, glutamate excitotoxicity, free radicals, and the inflammatory response contributing to the neurodegenerative process which is characterized by demyelination and apoptosis of neuronal tissue.",2016 Jun 23,"['Garcia, Elisa', 'Aguilar-Cevallos, Jorge', 'Silva-Garcia, Raul', 'Ibarra, Antonio']",Mediators Inflamm,,,True
3d9b665ff94e800c03f3051567312a3921a76e81,PMC,Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters,http://dx.doi.org/10.1128/JVI.00304-16,PMC4936146,27099308,CC BY,"Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, dysregulation of components of the immune response is often suggested as a possible cause. Alveolar macrophages are found in the alveoli of the lung and represent the first line of defense to many airborne pathogens. To determine whether alveolar macrophages play a role in HPS pathogenesis, alveolar macrophages were depleted in an adult rodent model of HPS that closely resembles human HPS. Syrian hamsters were treated, intratracheally, with clodronate-encapsulated liposomes or control liposomes and were then challenged with ANDV. Treatment with clodronate-encapsulated liposomes resulted in significant reduction in alveolar macrophages, but depletion did not prevent pathogenesis or prolong disease. Depletion also did not significantly reduce the amount of virus in the lung of ANDV-infected hamsters but altered neutrophil recruitment, MIP-1α and MIP-2 chemokine expression, and vascular endothelial growth factor (VEGF) levels in hamster bronchoalveolar lavage (BAL) fluid early after intranasal challenge. These data demonstrate that alveolar macrophages may play a limited protective role early after exposure to aerosolized ANDV but do not directly contribute to hantavirus disease pathogenesis in the hamster model of HPS. IMPORTANCE Hantaviruses continue to cause disease worldwide for which there are no FDA-licensed vaccines, effective postexposure prophylactics, or therapeutics. Much of this can be attributed to a poor understanding of the mechanism of hantavirus disease pathogenesis. Hantavirus disease has long been considered an immune-mediated disease; however, by directly manipulating the Syrian hamster model, we continue to eliminate individual immune cell types. As the most numerous immune cells present in the respiratory tract, alveolar macrophages are poised to defend against hantavirus infection, but those antiviral responses may also contribute to hantavirus disease. Here, we demonstrate that, like in our prior T and B cell studies, alveolar macrophages neither prevent hantavirus infection nor cause hantavirus disease. While these studies reflect pathogenesis in the hamster model, they should help us rule out specific cell types and prompt us to consider other potential mechanisms of disease in an effort to improve the outcome of human HPS.",2016 Jun 24,"['Hammerbeck, Christopher D.', 'Brocato, Rebecca L.', 'Bell, Todd M.', 'Schellhase, Christopher W.', 'Mraz, Steven R.', 'Queen, Laurie A.', 'Hooper, Jay W.']",J Virol,,,True
6fb5ec70b6d25243856c076c05809c2ed9d49bf1,PMC,A novel role for poly(C) binding proteins in programmed ribosomal frameshifting,http://dx.doi.org/10.1093/nar/gkw480,PMC4937337,27257056,CC BY,"Translational control through programmed ribosomal frameshifting (PRF) is exploited widely by viruses and increasingly documented in cellular genes. Frameshifting is induced by mRNA secondary structures that compromise ribosome fidelity during decoding of a heptanucleotide ‘slippery’ sequence. The nsp2 PRF signal of porcine reproductive and respiratory syndrome virus is distinctive in directing both −2 and −1 PRF and in its requirement for a trans-acting protein factor, the viral replicase subunit nsp1β. Here we show that the the trans-activation of frameshifting is carried out by a protein complex composed of nsp1β and a cellular poly(C) binding protein (PCBP). From the results of in vitro translation and electrophoretic mobility shift assays, we demonstrate that a PCBP/nsp1β complex binds to a C-rich sequence downstream of the slippery sequence and here mimics the activity of a structured mRNA stimulator of PRF. This is the first description of a role for a trans-acting cellular protein in PRF. The discovery broadens the repertoire of activities associated with poly(C) binding proteins and prototypes a new class of virus–host interactions.",2016 Jul 8,"['Napthine, Sawsan', 'Treffers, Emmely E.', 'Bell, Susanne', 'Goodfellow, Ian', 'Fang, Ying', 'Firth, Andrew E.', 'Snijder, Eric J.', 'Brierley, Ian']",Nucleic Acids Res,,,True
dcd1759241f327b5235520cebe1f7432aa936c5d,PMC,A novel role for poly(C) binding proteins in programmed ribosomal frameshifting,http://dx.doi.org/10.1093/nar/gkw480,PMC4937337,27257056,CC BY,"Translational control through programmed ribosomal frameshifting (PRF) is exploited widely by viruses and increasingly documented in cellular genes. Frameshifting is induced by mRNA secondary structures that compromise ribosome fidelity during decoding of a heptanucleotide ‘slippery’ sequence. The nsp2 PRF signal of porcine reproductive and respiratory syndrome virus is distinctive in directing both −2 and −1 PRF and in its requirement for a trans-acting protein factor, the viral replicase subunit nsp1β. Here we show that the the trans-activation of frameshifting is carried out by a protein complex composed of nsp1β and a cellular poly(C) binding protein (PCBP). From the results of in vitro translation and electrophoretic mobility shift assays, we demonstrate that a PCBP/nsp1β complex binds to a C-rich sequence downstream of the slippery sequence and here mimics the activity of a structured mRNA stimulator of PRF. This is the first description of a role for a trans-acting cellular protein in PRF. The discovery broadens the repertoire of activities associated with poly(C) binding proteins and prototypes a new class of virus–host interactions.",2016 Jul 8,"['Napthine, Sawsan', 'Treffers, Emmely E.', 'Bell, Susanne', 'Goodfellow, Ian', 'Fang, Ying', 'Firth, Andrew E.', 'Snijder, Eric J.', 'Brierley, Ian']",Nucleic Acids Res,,,True
2e50303039d019b3f817743da8a21e60f3b99130,PMC,"Two Multiplex Real-Time PCR Assays to Detect and Differentiate Acinetobacter baumannii and Non- baumannii Acinetobacter spp. Carrying bla(NDM), bla(OXA-23-Like), bla(OXA-40-Like), bla(OXA-51-Like), and bla(OXA-58-Like) Genes",http://dx.doi.org/10.1371/journal.pone.0158958,PMC4938629,27391234,CC BY,"Nosocomial infections caused by Acinetobacter spp. resistant to carbapenems are increasingly reported worldwide. Carbapenem-resistant Acinetobacter (CRA) is becoming a serious concern with increasing patient morbidity, mortality, and lengths of hospital stay. Therefore, the rapid detection of CRA is essential for epidemiological surveillance. Polymerase chain reaction (PCR) has been extensively used for the rapid identification of most pathogens. In this study, we have developed two multiplex real-time PCR assays to detect and differentiate A. baumannii and non-A. baumannii Acinetobacter spp, and common carbapenemase genes, including bla(NDM), bla(OXA-23-like), bla(OXA-40-like), bla(OXA-51-like), and bla(OXA-58-like). We demonstrate the potential utility of these assays for the direct detection of bla(NDM)-, bla(OXA-23-like)-, bla(OXA-40-like)-, bla(OXA-51-like)-, and bla(OXA-58-like)-positive CRA in clinical specimens. Primers were specifically designed, and two multiplex real-time PCR assays were developed: multiplex real-time PCR assay1 for the detection of Acinetobacter baumannii 16S–23S rRNA internal transcribed spacer sequence, the Acinetobacter recA gene, and class-B-metalloenzyme-encoding gene bla(NDM); and multiplex real-time PCR assay2 to detect class-D-oxacillinase-encoding genes (bla(OXA-23-like), bla(OXA-40-like), bla(OXA-51-like),and bla(OXA-58-like)). The assays were performed on an ABI Prism 7500 FAST Real-Time PCR System. CRA isolates were used to compare the assays with conventional PCR and sequencing. Known amounts of CRA cells were added to sputum and fecal specimens and used to test the multiplex real-time PCR assays. The results for target and nontarget amplification showed that the multiplex real-time PCR assays were specific, the limit of detection for each target was 10 copies per 20 μL reaction volume, the assays were linear over six log dilutions of the target genes (r(2) > 0.99), and the Ct values of the coefficients of variation for intra- and interassay reproducibility were less than 5%. The multiplex real-time PCR assays showed 100% concordance with conventional PCR when tested against 400 CRA isolates and their sensitivity for the target DNA in sputum and fecal specimens was 10(2) CFU/mL. Therefore, these novel multiplex real-time PCR assays allow the sensitive and specific characterization and differentiation of bla(NDM)-, bla(OXA-23-like)-, bla(OXA-40-like)-, bla(OXA-51-like)-, and bla(OXA-58-like)-positive CRA, making them potential tools for the direct detection of CRA in clinical specimens and the surveillance of nosocomial infections.",2016 Jul 8,"['Yang, Qiu', 'Rui, Yongyu']",PLoS One,,,True
48ac03386c65d4912b6455b123bde25f6e48f68c,PMC,Association of sputum microbiota profiles with severity of community-acquired pneumonia in children,http://dx.doi.org/10.1186/s12879-016-1670-4,PMC4939047,27391033,CC BY,"BACKGROUND: Competitive interactions among bacteria in the respiratory tract microbiota influence which species can colonize and potentially contribute to pathogenesis of community-acquired pneumonia (CAP). However, understanding of the role of respiratory tract microbiota in the clinical course of pediatric CAP is limited. METHODS: We sought to compare microbiota profiles in induced sputum and nasopharyngeal/oropharyngeal (NP/OP) samples from children and to identify microbiota profiles associated with CAP severity. We used 16S ribosomal RNA sequencing and several measures of microbiota profiles, including principal component analysis (PCA), to describe the respiratory microbiota in 383 children, 6 months to <18 years, hospitalized with CAP. We examined associations between induced sputum and NP/OP microbiota profiles and CAP severity (hospital length of stay and intensive care unit admission) using logistic regression. RESULTS: Relative abundance of bacterial taxa differed in induced sputum and NP/OP samples. In children 6 months to < 5 years, the sputum PCA factor with high relative abundance of Actinomyces, Veillonella, Rothia, and Lactobacillales was associated with decreased odds of length of stay ≥ 4 days [adjusted odds ratio (aOR) 0.69; 95 % confidence interval (CI) 0.48–0.99]. The sputum factor with high relative abundance of Haemophilus and Pasteurellaceae was associated with increased odds of intensive care unit admission [aOR 1.52; 95 % CI 1.02–2.26]. In children 5 to < 18 years, the sputum factor with high relative abundance of Porphyromonadaceae, Bacteriodales, Lactobacillales, and Prevotella was associated with increased odds of length of stay ≥ 4 days [aOR 1.52; 95 % CI 1.02–2.26]. Taxa in NP/OP samples were not associated with CAP severity. CONCLUSION: Certain taxa in the respiratory microbiota, which were detected in induced sputum samples, are associated with the clinical course of CAP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1670-4) contains supplementary material, which is available to authorized users.",2016 Jul 8,"['Pettigrew, Melinda M.', 'Gent, Janneane F.', 'Kong, Yong', 'Wade, Martina', 'Gansebom, Shane', 'Bramley, Anna M.', 'Jain, Seema', 'Arnold, Sandra L. R.', 'McCullers, Jonathan A.']",BMC Infect Dis,,,False
91faf9aa02611ff7e20a3c45babd11cdf0611a2b,PMC,Association of sputum microbiota profiles with severity of community-acquired pneumonia in children,http://dx.doi.org/10.1186/s12879-016-1670-4,PMC4939047,27391033,CC BY,"BACKGROUND: Competitive interactions among bacteria in the respiratory tract microbiota influence which species can colonize and potentially contribute to pathogenesis of community-acquired pneumonia (CAP). However, understanding of the role of respiratory tract microbiota in the clinical course of pediatric CAP is limited. METHODS: We sought to compare microbiota profiles in induced sputum and nasopharyngeal/oropharyngeal (NP/OP) samples from children and to identify microbiota profiles associated with CAP severity. We used 16S ribosomal RNA sequencing and several measures of microbiota profiles, including principal component analysis (PCA), to describe the respiratory microbiota in 383 children, 6 months to <18 years, hospitalized with CAP. We examined associations between induced sputum and NP/OP microbiota profiles and CAP severity (hospital length of stay and intensive care unit admission) using logistic regression. RESULTS: Relative abundance of bacterial taxa differed in induced sputum and NP/OP samples. In children 6 months to < 5 years, the sputum PCA factor with high relative abundance of Actinomyces, Veillonella, Rothia, and Lactobacillales was associated with decreased odds of length of stay ≥ 4 days [adjusted odds ratio (aOR) 0.69; 95 % confidence interval (CI) 0.48–0.99]. The sputum factor with high relative abundance of Haemophilus and Pasteurellaceae was associated with increased odds of intensive care unit admission [aOR 1.52; 95 % CI 1.02–2.26]. In children 5 to < 18 years, the sputum factor with high relative abundance of Porphyromonadaceae, Bacteriodales, Lactobacillales, and Prevotella was associated with increased odds of length of stay ≥ 4 days [aOR 1.52; 95 % CI 1.02–2.26]. Taxa in NP/OP samples were not associated with CAP severity. CONCLUSION: Certain taxa in the respiratory microbiota, which were detected in induced sputum samples, are associated with the clinical course of CAP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1670-4) contains supplementary material, which is available to authorized users.",2016 Jul 8,"['Pettigrew, Melinda M.', 'Gent, Janneane F.', 'Kong, Yong', 'Wade, Martina', 'Gansebom, Shane', 'Bramley, Anna M.', 'Jain, Seema', 'Arnold, Sandra L. R.', 'McCullers, Jonathan A.']",BMC Infect Dis,,,False
18d6b41f2b9f5cad93519eb39f422f7f008a4ed3,PMC,Association of sputum microbiota profiles with severity of community-acquired pneumonia in children,http://dx.doi.org/10.1186/s12879-016-1670-4,PMC4939047,27391033,CC BY,"BACKGROUND: Competitive interactions among bacteria in the respiratory tract microbiota influence which species can colonize and potentially contribute to pathogenesis of community-acquired pneumonia (CAP). However, understanding of the role of respiratory tract microbiota in the clinical course of pediatric CAP is limited. METHODS: We sought to compare microbiota profiles in induced sputum and nasopharyngeal/oropharyngeal (NP/OP) samples from children and to identify microbiota profiles associated with CAP severity. We used 16S ribosomal RNA sequencing and several measures of microbiota profiles, including principal component analysis (PCA), to describe the respiratory microbiota in 383 children, 6 months to <18 years, hospitalized with CAP. We examined associations between induced sputum and NP/OP microbiota profiles and CAP severity (hospital length of stay and intensive care unit admission) using logistic regression. RESULTS: Relative abundance of bacterial taxa differed in induced sputum and NP/OP samples. In children 6 months to < 5 years, the sputum PCA factor with high relative abundance of Actinomyces, Veillonella, Rothia, and Lactobacillales was associated with decreased odds of length of stay ≥ 4 days [adjusted odds ratio (aOR) 0.69; 95 % confidence interval (CI) 0.48–0.99]. The sputum factor with high relative abundance of Haemophilus and Pasteurellaceae was associated with increased odds of intensive care unit admission [aOR 1.52; 95 % CI 1.02–2.26]. In children 5 to < 18 years, the sputum factor with high relative abundance of Porphyromonadaceae, Bacteriodales, Lactobacillales, and Prevotella was associated with increased odds of length of stay ≥ 4 days [aOR 1.52; 95 % CI 1.02–2.26]. Taxa in NP/OP samples were not associated with CAP severity. CONCLUSION: Certain taxa in the respiratory microbiota, which were detected in induced sputum samples, are associated with the clinical course of CAP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1670-4) contains supplementary material, which is available to authorized users.",2016 Jul 8,"['Pettigrew, Melinda M.', 'Gent, Janneane F.', 'Kong, Yong', 'Wade, Martina', 'Gansebom, Shane', 'Bramley, Anna M.', 'Jain, Seema', 'Arnold, Sandra L. R.', 'McCullers, Jonathan A.']",BMC Infect Dis,,,True
6908a089fea0a7345e066dfd10462507601d88eb,PMC,"Complete Genome Sequence of Porcine Epidemic Diarrhea Virus from an Outbreak in a Vaccinated Farm in Shandong, China",http://dx.doi.org/10.1128/genomeA.00619-16,PMC4939784,27389267,CC BY,"Porcine epidemic diarrhea virus, a member of the family Coronaviridae, is an economically important pathogen that causes severe enteritis, vomiting, dehydration, and a high mortality rate, especially among suckling piglets. Here, we report the complete genome sequence (28,036 nucleotides [nt]) of a porcine epidemic diarrhea virus (PEDV) strain isolated in a novel outbreak in Shandong, China.",2016 Jul 7,"['Gao, Xiang', 'Li, Dongliang', 'Zhao, Jingyi', 'Xu, Farong', 'Ge, Xinna', 'Guo, Xin', 'Han, Jun', 'Yang, Hanchun', 'Zhou, Lei']",Genome Announc,,,True
714e40f88f6e629f0f63574ec52ea967aeee4065,PMC,Cryo-electron Microscopy Structure of the Native Prototype Foamy Virus Glycoprotein and Virus Architecture,http://dx.doi.org/10.1371/journal.ppat.1005721,PMC4939959,27399201,CC BY,"Foamy viruses (FV) belong to the genus Spumavirus, which forms a distinct lineage in the Retroviridae family. Although the infection in natural hosts and zoonotic transmission to humans is asymptomatic, FVs can replicate well in human cells making it an attractive gene therapy vector candidate. Here we present cryo-electron microscopy and (cryo-)electron tomography ultrastructural data on purified prototype FV (PFV) and PFV infected cells. Mature PFV particles have a distinct morphology with a capsid of constant dimension as well as a less ordered shell of density between the capsid and the membrane likely formed by the Gag N-terminal domain and the cytoplasmic part of the Env leader peptide gp18(LP). The viral membrane contains trimeric Env glycoproteins partly arranged in interlocked hexagonal assemblies. In situ 3D reconstruction by subtomogram averaging of wild type Env and of a Env gp48(TM)- gp80(SU) cleavage site mutant showed a similar spike architecture as well as stabilization of the hexagonal lattice by clear connections between lower densities of neighboring trimers. Cryo-EM was employed to obtain a 9 Å resolution map of the glycoprotein in its pre-fusion state, which revealed extensive trimer interactions by the receptor binding subunit gp80(SU) at the top of the spike and three central helices derived from the fusion protein subunit gp48(TM). The lower part of Env, presumably composed of interlaced parts of gp48(TM), gp80(SU) and gp18(LP) anchors the spike at the membrane. We propose that the gp48(TM) density continues into three central transmembrane helices, which interact with three outer transmembrane helices derived from gp18(LP). Our ultrastructural data and 9 Å resolution glycoprotein structure provide important new insights into the molecular architecture of PFV and its distinct evolutionary relationship with other members of the Retroviridae.",2016 Jul 11,"['Effantin, Grégory', 'Estrozi, Leandro F.', 'Aschman, Nick', 'Renesto, Patricia', 'Stanke, Nicole', 'Lindemann, Dirk', 'Schoehn, Guy', 'Weissenhorn, Winfried']",PLoS Pathog,,,True
84bb5b317c837c22b090bc10357a3542f58402bd,PMC,Genetic characterization of commensal Escherichia coli isolated from laboratory rodents,http://dx.doi.org/10.1186/s40064-016-2745-9,PMC4940358,27462483,CC BY,"BACKGROUND: Escherichia coli, a commensal in the intestines of vertebrates, is capable of colonizing many different hosts and the environment. Commensal E. coli strains are believed to be the precursor of pathogenic strains by means of acquisition of antimicrobial resistant and virulence genes. Laboratory rodents are inherently susceptible to numerous known infectious agents, which could transfer virulence determinants to commensal E. coli. Hence, in this study, the genetic structure of commensal E. coli found in laboratory rodents and their antimicrobial resistance profiles were investigated. RESULTS: E. coli strains belonging to phylogroup A were the predominant strain obtained from the animals used in the study. Four novel sequence types (ST746, ST747, ST748 and ST749) were discovered using the multi locus sequence typing, together with one common ST357 in the gastrointestinal tract, liver and, the trachea and lung. Serotyping demonstrated that these commensal E. coli strains were non-Shiga toxin-producers. Phenotypic and genotypic analyses of extended spectrum beta lactamases were also negative. CONCLUSIONS: These findings implied that the E. coli strains recovered from the laboratory rodents were truly commensal in nature. Further study is required to investigate the possible influence of gender on the susceptibility of hosts to E. coli colonization in laboratory rodents. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-016-2745-9) contains supplementary material, which is available to authorized users.",2016 Jul 11,"['Loong, Shih Keng', 'Mahfodz, Nur Hidayana', 'Che Mat Seri, Nurul Asma Anati', 'Mohamad Wali, Haryanti Azura', 'Abd Gani, Syahar Amir', 'Wong, Pooi-Fong', 'AbuBakar, Sazaly']",Springerplus,,,True
4a8a6f65da6c9eca4117de59c6377a0ff02a0d09,PMC,"Efficacy, Safety, and Pharmacokinetics of a New 10 % Liquid Intravenous Immunoglobulin Containing High Titer Neutralizing Antibody to RSV and Other Respiratory Viruses in Subjects with Primary Immunodeficiency Disease",http://dx.doi.org/10.1007/s10875-016-0308-z,PMC4940435,27324887,CC BY,"PURPOSE: Immune globulins for IgG supplementation have been produced for over 35 years with essentially no differentiating features regarding their specific antibody composition. Furthermore, the compositions of plasma donor pools used for IG manufacturing are not standardized. While all immune globulin products meet the specifications set by the US FDA for antibodies to pathogens like measles and polio, they have variable levels of antibodies to other important viruses and infectious pathogens, particularly respiratory syncytial virus (RSV). METHODS: An IVIG was developed that satisfies the requirements for treating patients with primary immune deficiency disease (PIDD) and also has standardized elevated levels of RSV neutralizing antibodies (RI-002). Plasma donors who have naturally occurring high circulating levels of neutralizing anti-RSV antibody were selected as the source for manufacturing IVIG to treat patients with PIDD to prevent serious bacterial infections. While the introduction of the monoclonal antibody Palivizumab has had a dramatic impact in diminishing the burden of RSV disease in the pediatric population, it does not meet the standards for replacing the deficient immune compartments of patients with PIDD. RESULTS: Fifty-nine patients with PIDD at 9 different sites across the US were enrolled in this study and received regular infusions of RI-002 over the course of 1 year. CONCLUSIONS: There were zero serious bacterial infections, thus meeting the primary endpoint for this trial. The secondary endpoints including days missed from work due to infection, unscheduled visits to the physician, and days of hospitalization due to infection compared favorably to published reports of other IVIG products.",2016 Jun 20,"['Wasserman, Richard L.', 'Lumry, William', 'Harris, James', 'Levy, Robyn', 'Stein, Mark', 'Forbes, Lisa', 'Cunningham-Rundles, Charlotte', 'Melamed, Isaac', 'Kobayashi, Ai Lan', 'Du, Wei', 'Kobayashi, Roger']",J Clin Immunol,,,True
4fcb098e746e236ebc700fc79262c3263550b3d9,PMC,Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches,http://dx.doi.org/10.1038/srep29680,PMC4940736,27403722,CC BY,"The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18β-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18β-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development.",2016 Jul 12,"['Fu, Xu', 'Wang, Zhihua', 'Li, Lixin', 'Dong, Shishang', 'Li, Zhucui', 'Jiang, Zhenzuo', 'Wang, Yuefei', 'Shui, Wenqing']",Sci Rep,,,True
370500e606926d13ff711d404ee1d7cafa6c3c1c,PMC,Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches,http://dx.doi.org/10.1038/srep29680,PMC4940736,27403722,CC BY,"The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18β-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18β-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development.",2016 Jul 12,"['Fu, Xu', 'Wang, Zhihua', 'Li, Lixin', 'Dong, Shishang', 'Li, Zhucui', 'Jiang, Zhenzuo', 'Wang, Yuefei', 'Shui, Wenqing']",Sci Rep,,,False
b314e4a20b1f0a2f4a49afb65c17859ad7d50c4d,PMC,CCR5 knockout suppresses experimental autoimmune encephalomyelitis in C57BL/6 mice,http://dx.doi.org/10.18632/oncotarget.8097,PMC4941248,26985768,CC BY,"Multiple sclerosis (MS) is an inflammatory disease in which myelin in the spinal cord is damaged. C-C chemokine receptor type 5 (CCR5) is implicated in immune cell migration and cytokine release in central nervous system (CNS). We investigated whether CCR5 plays a role in MS progression using a murine model, experimental autoimmune encephalomyelitis (EAE), in CCR5 deficient (CCR5(−/−)) mice. CCR5(−/−) and CCR5(+/+) (wild-type) mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG(35-55)) followed by pertussis toxin, after which EAE paralysis was scored for 28 days. We found that clinical scoring and EAE neuropathology were lower in CCR5(−/−) mice than CCR5(+/+) mice. Immune cells (CD3(+), CD4(+), CD8(+), B cell, NK cell and macrophages) infiltration and astrocytes/microglial activation were attenuated in CCR5(−/−) mice. Moreover, levels of IL-1β, TNF-α, IFN-γ and MCP-1 cytokine levels were decreased in CCR5(−/−) mice spinal cord. Myelin basic protein (MBP) and CNPase were increased while NG2 and O4 were decreased in CCR5(−/−) mice, indicating that demyelination was suppressed by CCR5 gene deletion. These findings suggest that CCR5 is likely participating in demyelination in the spinal cord the MS development, and that it could serve as an effective therapeutic target for the treatment of MS.",2016 Mar 15,"['Gu, Sun Mi', 'Park, Mi Hee', 'Yun, Hyung Mun', 'Han, Sang Bae', 'Oh, Ki Wan', 'Son, Dong Ju', 'Yun, Jae Suk', 'Hong, Jin Tae']",Oncotarget,,,True
6f3dddc4c061491fb43651e9bb61039ac7594a78,PMC,CCR5 knockout suppresses experimental autoimmune encephalomyelitis in C57BL/6 mice,http://dx.doi.org/10.18632/oncotarget.8097,PMC4941248,26985768,CC BY,"Multiple sclerosis (MS) is an inflammatory disease in which myelin in the spinal cord is damaged. C-C chemokine receptor type 5 (CCR5) is implicated in immune cell migration and cytokine release in central nervous system (CNS). We investigated whether CCR5 plays a role in MS progression using a murine model, experimental autoimmune encephalomyelitis (EAE), in CCR5 deficient (CCR5(−/−)) mice. CCR5(−/−) and CCR5(+/+) (wild-type) mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG(35-55)) followed by pertussis toxin, after which EAE paralysis was scored for 28 days. We found that clinical scoring and EAE neuropathology were lower in CCR5(−/−) mice than CCR5(+/+) mice. Immune cells (CD3(+), CD4(+), CD8(+), B cell, NK cell and macrophages) infiltration and astrocytes/microglial activation were attenuated in CCR5(−/−) mice. Moreover, levels of IL-1β, TNF-α, IFN-γ and MCP-1 cytokine levels were decreased in CCR5(−/−) mice spinal cord. Myelin basic protein (MBP) and CNPase were increased while NG2 and O4 were decreased in CCR5(−/−) mice, indicating that demyelination was suppressed by CCR5 gene deletion. These findings suggest that CCR5 is likely participating in demyelination in the spinal cord the MS development, and that it could serve as an effective therapeutic target for the treatment of MS.",2016 Mar 15,"['Gu, Sun Mi', 'Park, Mi Hee', 'Yun, Hyung Mun', 'Han, Sang Bae', 'Oh, Ki Wan', 'Son, Dong Ju', 'Yun, Jae Suk', 'Hong, Jin Tae']",Oncotarget,,,False
109a7800d93fdf2a2c64a261aab1182dd5b607af,PMC,The pathogenesis of multifocal osteonecrosis,http://dx.doi.org/10.1038/srep29576,PMC4941719,27404962,CC BY,"Our objective was to study the incidence, etiology, and diagnosis of multifocal osteonecrosis (MFON) and its treatment options to facilitate an earlier diagnosis and to optimize treatment. A radiological investigation was performed in osteonecrosis patients with a high risk of MFON for a more accurate diagnosis between January 2010 and June 2015. For patients with osteonecrosis of both the hip and knee joints or for patients with a history of corticosteroid use or alcohol abuse who had osteonecrosis of one or more joints in the shoulder, ankle, wrist or elbow, magnetic resonance imaging (MRI) was also performed on other joints, regardless of whether these joints were symptomatic. Furthermore, we performed a radiological screening of 102 patients who had a negative diagnosis of MFON but were at a high risk; among them, another 31 MFON cases were successfully identified (30.4%). Thus, the incidence of MFON during the study period increased from 3.1% to 5.2%. Patients diagnosed with osteonecrosis and who are at a high risk of MFON should have their other joints radiologically examined when necessary. This will reduce missed diagnosis of MFON and facilitate an earlier diagnosis and treatment to achieve an optimal outcome.",2016 Jul 11,"['Sun, Wei', 'Shi, Zhencai', 'Gao, Fuqiang', 'Wang, Bailiang', 'Li, Zirong']",Sci Rep,,,True
31c0ee2b6dff1699d251316667c0b56c7b8f09a3,PMC,Host protective ASP-based vaccine against the parasitic nematode Ostertagia ostertagi triggers NK cell activation and mixed IgG1-IgG2 response,http://dx.doi.org/10.1038/srep29496,PMC4941725,27403891,CC BY,"The mucus-dwelling parasite Ostertagia ostertagi is one of the most important gastrointestinal nematodes in cattle. Our group has previously demonstrated the protective capacity of a vaccine against this parasite based on a native activation-associated secreted protein ASP1 (nASP) in combination with the saponin adjuvant QuilA. The aim of the current study was to analyse the effect of both antigen and adjuvant on the cellular and humoral vaccine-induced immune responses by comparing the native ASP to a recombinant version expressed in Pichia pastoris (pASP) and replacing QuilA by Al(OH)(3). Immunization of cattle with the protective nASP+QuilA vaccine was associated with antigen-induced proliferation of natural killer (NK) cells combined with IFN-γ secretion and the induction of a mixed IgG1/IgG2 antibody response. ASP-specific activation and proliferation of NK cells was also observed in mice following the same vaccination regime. Replacing QuilA by Al(OH)(3) or nASP by pASP significantly decreased the capacity of the vaccines to trigger both NK cell activation and antibody responses and failed to induce protection against a challenge infection. Reduction of the structurally anchoring disulphide bonds of the nASP completely abolished its ability to induce NK cell activation and antibody responses, highlighting the importance of protein conformation for the immunostimulatory activity.",2016 Jul 11,"['González-Hernández, Ana', 'Van Coppernolle, Stefanie', 'Borloo, Jimmy', 'Van Meulder, Frederik', 'Paerewijck, Oonagh', 'Peelaers, Iris', 'Leclercq, Georges', 'Claerebout, Edwin', 'Geldhof, Peter']",Sci Rep,,,True
eb8cabb9a02a33566499d48341169eb6aa291b47,PMC,Host protective ASP-based vaccine against the parasitic nematode Ostertagia ostertagi triggers NK cell activation and mixed IgG1-IgG2 response,http://dx.doi.org/10.1038/srep29496,PMC4941725,27403891,CC BY,"The mucus-dwelling parasite Ostertagia ostertagi is one of the most important gastrointestinal nematodes in cattle. Our group has previously demonstrated the protective capacity of a vaccine against this parasite based on a native activation-associated secreted protein ASP1 (nASP) in combination with the saponin adjuvant QuilA. The aim of the current study was to analyse the effect of both antigen and adjuvant on the cellular and humoral vaccine-induced immune responses by comparing the native ASP to a recombinant version expressed in Pichia pastoris (pASP) and replacing QuilA by Al(OH)(3). Immunization of cattle with the protective nASP+QuilA vaccine was associated with antigen-induced proliferation of natural killer (NK) cells combined with IFN-γ secretion and the induction of a mixed IgG1/IgG2 antibody response. ASP-specific activation and proliferation of NK cells was also observed in mice following the same vaccination regime. Replacing QuilA by Al(OH)(3) or nASP by pASP significantly decreased the capacity of the vaccines to trigger both NK cell activation and antibody responses and failed to induce protection against a challenge infection. Reduction of the structurally anchoring disulphide bonds of the nASP completely abolished its ability to induce NK cell activation and antibody responses, highlighting the importance of protein conformation for the immunostimulatory activity.",2016 Jul 11,"['González-Hernández, Ana', 'Van Coppernolle, Stefanie', 'Borloo, Jimmy', 'Van Meulder, Frederik', 'Paerewijck, Oonagh', 'Peelaers, Iris', 'Leclercq, Georges', 'Claerebout, Edwin', 'Geldhof, Peter']",Sci Rep,,,False
2618f1868d3eaf92f7f306467b9c8d91ec7572ba,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,True
7e631e260a55ab4d59f63b26e52751a887b43749,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
9d2d67ed3a51962962399189441bf8e56b1c8f05,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
013e59d78b56b934b608e1ab2af766f6cbf5767c,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
3cf75eb0fab0b107484f83f5d2bde3a7100f9b9e,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
1058752cdbce833369e36bd54533bd5877b298eb,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
17c2c7b70fdaa3c6c0458580631056cf502b1b2b,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
2c8f174dd3e9c36ae7f49f4fcbf25b36b89f3d6e,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
fab4063e3f79d8f35d31cd5a26a93d0cbcd57186,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
6ee96231a86e71b65721eb972d03ef12dcbd5251,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
5e82264bcbfc8321618fa3d4b8d1c5cf165c2e93,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
d28644b207846776f4a9c6829a5167b0371797bd,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
efb13e65adfd16cd39afcea3dde4b0a83a26ad53,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
e881ac8842076e240f5a8612630f099d8e273e05,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
63f2edb69f2f971520167144c280cb6d70f0f884,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
819b587f7250e5bb2470826cfb87ad311aab711e,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
036f6cd2baef44fb73ab5664e3a1211f2b8c2f1c,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
cb7351d6e0190d59cb0bd93ddbdebbe10c6d4958,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
c815c7fc324a6ac8e11e6c7eba2289e7fb368728,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
a51659a324f74a7cf16acd3b1180d203cab2b8d4,PMC,Profiling of Host Cell Response to Successive Canine Parvovirus Infection Based on Kinetic Proteomic Change Identification,http://dx.doi.org/10.1038/srep29560,PMC4942776,27406444,CC BY,"Canine parvovirus (CPV) reproduces by co-opting the resources of host cells, inevitably causing cytotoxic effects to the host cells. Feline kidney F81 cells are sensitive to CPV infection and show disparate growing statuses at different time points post-infection. This study analysed the response of F81 cells to CPV infection at successive infection time points by iTRAQ-based quantitative proteomics. Differentially expressed proteins (DEPs) during 60 h of infection and at selected time points post-infection were identified by an analysis of variance test and a two-tailed unpaired t test, respectively. DEPs with similar quantitative changes were clustered by hierarchical clustering and analysed by gene ontology enrichment, revealing that 12 h and 60 h post-infection were the optimal times to analyse the autonomous parvovirus replication and apoptosis processes, respectively. Using the Metacore(TM) database, 29 DEPs were enriched in a network involved in p53 regulation. Besides, a significantly enriched pathway suggests that the CPV-induced cytopathic effect was probably due to the deficiency of functional CFTR caused by CPV infection. This study uncovered the systemic changes in key cellular factors involved in CPV infection and help to understand the molecular mechanisms of the anti-cancer activity of CPV and the cytopathic effects induced by CPV infection.",2016 Jul 13,"['Zhao, Hang', 'Cheng, Yuening', 'Wang, Jianke', 'Lin, Peng', 'Yi, Li', 'Sun, Yaru', 'Ren, Jingqiang', 'Tong, Mingwei', 'Cao, Zhigang', 'Li, Jiawei', 'Deng, Jinliang', 'Cheng, Shipeng']",Sci Rep,,,True
044cd9bf656d1868e96d2213d947fff4561d0f7a,PMC,Profiling of Host Cell Response to Successive Canine Parvovirus Infection Based on Kinetic Proteomic Change Identification,http://dx.doi.org/10.1038/srep29560,PMC4942776,27406444,CC BY,"Canine parvovirus (CPV) reproduces by co-opting the resources of host cells, inevitably causing cytotoxic effects to the host cells. Feline kidney F81 cells are sensitive to CPV infection and show disparate growing statuses at different time points post-infection. This study analysed the response of F81 cells to CPV infection at successive infection time points by iTRAQ-based quantitative proteomics. Differentially expressed proteins (DEPs) during 60 h of infection and at selected time points post-infection were identified by an analysis of variance test and a two-tailed unpaired t test, respectively. DEPs with similar quantitative changes were clustered by hierarchical clustering and analysed by gene ontology enrichment, revealing that 12 h and 60 h post-infection were the optimal times to analyse the autonomous parvovirus replication and apoptosis processes, respectively. Using the Metacore(TM) database, 29 DEPs were enriched in a network involved in p53 regulation. Besides, a significantly enriched pathway suggests that the CPV-induced cytopathic effect was probably due to the deficiency of functional CFTR caused by CPV infection. This study uncovered the systemic changes in key cellular factors involved in CPV infection and help to understand the molecular mechanisms of the anti-cancer activity of CPV and the cytopathic effects induced by CPV infection.",2016 Jul 13,"['Zhao, Hang', 'Cheng, Yuening', 'Wang, Jianke', 'Lin, Peng', 'Yi, Li', 'Sun, Yaru', 'Ren, Jingqiang', 'Tong, Mingwei', 'Cao, Zhigang', 'Li, Jiawei', 'Deng, Jinliang', 'Cheng, Shipeng']",Sci Rep,,,False
a280d2019f9957487f81e4c5cf2d94a2a2f391a6,PMC,Feasibility of a randomized controlled trial to assess treatment of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Saudi Arabia: a survey of physicians,http://dx.doi.org/10.1186/s12871-016-0198-x,PMC4942900,27405596,CC BY,"BACKGROUND: The Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging respiratory pathogen with a high mortality rate and no specific treatments available to date. The purpose of this study was to determine the feasibility of conducting a randomized controlled trial (RCT) of convalescent plasma therapy for MERS-CoV-infected patients by using MERS-CoV-specific convalescent plasma obtained from previously recovered patients. METHODS: A survey was adapted from validated questionnaire originally aimed to measure network capacities and capabilities within the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC). The questionnaire was modified for this study to include 26 items that were divided into three main domains of interest: (1) the ability to care for critically ill MERS-CoV patients; (2) laboratory capacity to diagnose MERS-CoV and blood bank ability to prepare convalescent plasma; and (3), research capacity to conduct randomized controlled trials. The questionnaire was emailed to physicians. RESULTS: Of 582 physicians who were invited to the survey, 327 responded (56.2 %). The professional focus of the majority of respondents was critical care (106/249 (43 %)), pediatrics (59/249, (24 %)) or internal medicine (52/249 (21 %)) but none was blood banking. Nearly all respondents (251/263 (95 %)) reported to have access to ICU facilities within their institutions. Most respondents (219/270 (81 %)) reported that intensivists were the most physician group responsible for treatment decisions about critically ill SARI patients. While 125/165 respondents (76 %) reported that they conduct research in ICUs, and 80/161 (49.7 %) had been involved in the conduct of RCTs, including using a placebo comparison (60/161 (37 %)), only 49/226 (21 %) of respondents regularly participated in research networks. CONCLUSIONS: Our survey indicated that in the Kingdom of Saudi Arabia (KSA), ICUs are the most likely clinical locations for conducting a clinical trial of convalescent plasma therapy for MERS-CoV, and that most ICUs have experience with such research designs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12871-016-0198-x) contains supplementary material, which is available to authorized users.",2016 Jul 12,"['Arabi, Yaseen M.', 'Al-Enezi, Farhan', 'Longuere, Kajsa-Stina', 'Balkhy, Hanan H.', 'Al-Sultan, Mohamed', 'Al-Omari, Awad', 'Al-Hameed, Fahad M.', 'Carson, Gail', 'Shindo, Nahoko', 'Fowler, Robert']",BMC Anesthesiol,,,True
7636da046a6bdf1033f9078671187e65e0e231d9,PMC,Body surface infrared thermometry in patients with central venous cateter-related infections,http://dx.doi.org/10.1590/S1679-45082015AO3397,PMC4943780,26466058,CC BY,"OBJECTIVE: To evaluate if body surface temperature close to the central venous catheter insertion area is different when patients develop catheter-related bloodstream infections. METHODS: Observational cross-sectional study. Using a non-contact infrared thermometer, 3 consecutive measurements of body surface temperature were collected from 39 patients with central venous catheter on the following sites: nearby the catheter insertion area or totally implantable catheter reservoir, the equivalent contralateral region (without catheter), and forehead of the same subject. RESULTS: A total of 323 observations were collected. Respectively, both in male and female patients, disregarding the occurrence of infection, the mean temperature on the catheter area minus that on the contralateral region (mean ± standard deviation: -0.3±0.6°C versus -0.2±0.5ºC; p=0.36), and the mean temperature on the catheter area minus that on the forehead (mean ± standard deviation: -0.2±0.5°C versus -0.1±0.5ºC; p=0.3) resulted in negative values. Moreover, in infected patients, higher values were obtained on the catheter area (95%CI: 36.6-37.5ºC versus 36.3-36.5ºC; p<0.01) and by temperature subtractions: catheter area minus contralateral region (95%CI: -0.17 - +0.33ºC versus -0.33 - -0.20ºC; p=0.02) and catheter area minus forehead (95%CI: -0.02 - +0.55ºC versus -0.22 - -0.10ºC; p<0.01). CONCLUSION: Using a non-contact infrared thermometer, patients with catheter-related bloodstream infections had higher temperature values both around catheter insertion area and in the subtraction of the temperatures on the contralateral and forehead regions from those on the catheter area.",2015 Jul-Sep,"['Silvah, José Henrique', 'de Lima, Cristiane Maria Mártires', 'de Unamuno, Maria do Rosário Del Lama', 'Schetino, Marco Antônio Alves', 'Schetino, Luana Pereira Leite', 'Fassini, Priscila Giácomo', 'Brandão, Camila Fernanda Costa e Cunha Moraes', 'Basile, Anibal', 'da Cunha, Selma Freire Carvalho', 'Marchini, Julio Sergio']",Einstein (Sao Paulo),,,True
7acba31dde3af3dc1bedbde1c8167ad802fbf43e,PMC,"Productive replication of nephropathogenic infectious bronchitis virus in peripheral blood monocytic cells, a strategy for viral dissemination and kidney infection in chickens",http://dx.doi.org/10.1186/s13567-016-0354-9,PMC4944500,27412035,CC BY,"In the present study, the replication kinetics of nephropathogenic (B1648) and respiratory (Massachusetts-M41) IBV strains were compared in vitro in respiratory mucosa explants and blood monocytes (KUL01(+) cells), and in vivo in chickens to understand why some IBV strains have a kidney tropism. B1648 was replicating somewhat better than M41 in the epithelium of the respiratory mucosa explants and used more KUL01(+) cells to penetrate the deeper layers of the respiratory tract. B1648 was productively replicating in KUL01(+) monocytic cells in contrast with M41. In B1648 inoculated animals, 10(2.7–6.8) viral RNA copies/100 mg were detected in tracheal secretions at 2, 4, 6, 8, 10 and 12 days post inoculation (dpi), 10(2.4–4.5) viral RNA copies/mL in plasma at 2, 4, 6, 8, 10 and 12 dpi and 10(1.8–4.4) viral RNA copies/10(6) mononuclear cells in blood at 2, 4, 6 and 8 dpi. In M41 inoculated animals, 10(2.6–7.0) viral RNA copies/100 mg were detected in tracheal secretions at 2, 4, 6, 8 and 10 dpi, but viral RNA was not demonstrated in plasma and mononuclear cells (except in one chicken at 6 dpi). Infectious virus was detected only in plasma and mononuclear cells of the B1648 group. At euthanasia (12 dpi), viral RNA and antigen positive cells were detected in lungs, liver, spleen and kidneys of only the B1648 group and in tracheas of both the B1648 and M41 group. In conclusion, only B1648 can easily disseminate to internal organs via a cell-free and -associated viremia with KUL01(+) cells as important carrier cells.",2016 Jul 13,"['Reddy, Vishwanatha R. A. P.', 'Trus, Ivan', 'Desmarets, Lowiese M. B.', 'Li, Yewei', 'Theuns, Sebastiaan', 'Nauwynck, Hans J.']",Vet Res,,,True
88a48452ce073c9968ca2e2794fc0bccfb5dfc0f,PMC,Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding,http://dx.doi.org/10.1371/journal.pone.0159074,PMC4944999,27415624,CC BY,"Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/Mute Swan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis. The peptides and their derivatives are of great potential for drug development as well as biosensing.",2016 Jul 14,"['Memczak, Henry', 'Lauster, Daniel', 'Kar, Parimal', 'Di Lella, Santiago', 'Volkmer, Rudolf', 'Knecht, Volker', 'Herrmann, Andreas', 'Ehrentreich-Förster, Eva', 'Bier, Frank F.', 'Stöcklein, Walter F. M.']",PLoS One,,,True
07ac15697a17a271224c7477de061f4ca6fc62aa,PMC,Topological Small-World Organization of the Fibroblastic Reticular Cell Network Determines Lymph Node Functionality,http://dx.doi.org/10.1371/journal.pbio.1002515,PMC4945005,27415420,CC BY,"Fibroblastic reticular cells (FRCs) form the cellular scaffold of lymph nodes (LNs) and establish distinct microenvironmental niches to provide key molecules that drive innate and adaptive immune responses and control immune regulatory processes. Here, we have used a graph theory-based systems biology approach to determine topological properties and robustness of the LN FRC network in mice. We found that the FRC network exhibits an imprinted small-world topology that is fully regenerated within 4 wk after complete FRC ablation. Moreover, in silico perturbation analysis and in vivo validation revealed that LNs can tolerate a loss of approximately 50% of their FRCs without substantial impairment of immune cell recruitment, intranodal T cell migration, and dendritic cell-mediated activation of antiviral CD8(+) T cells. Overall, our study reveals the high topological robustness of the FRC network and the critical role of the network integrity for the activation of adaptive immune responses.",2016 Jul 14,"['Novkovic, Mario', 'Onder, Lucas', 'Cupovic, Jovana', 'Abe, Jun', 'Bomze, David', 'Cremasco, Viviana', 'Scandella, Elke', 'Stein, Jens V.', 'Bocharov, Gennady', 'Turley, Shannon J.', 'Ludewig, Burkhard']",PLoS Biol,,,True
ac7d8fb495888876f03df56a1d3a3faa1f05e770,PMC,Inhibition of the Hantavirus Fusion Process by Predicted Domain III and Stem Peptides from Glycoprotein Gc,http://dx.doi.org/10.1371/journal.pntd.0004799,PMC4945073,27414047,CC BY,"Hantaviruses can cause hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome in humans. To enter cells, hantaviruses fuse their envelope membrane with host cell membranes. Previously, we have shown that the Gc envelope glycoprotein is the viral fusion protein sharing characteristics with class II fusion proteins. The ectodomain of class II fusion proteins is composed of three domains connected by a stem region to a transmembrane anchor in the viral envelope. These fusion proteins can be inhibited through exogenous fusion protein fragments spanning domain III (DIII) and the stem region. Such fragments are thought to interact with the core of the fusion protein trimer during the transition from its pre-fusion to its post-fusion conformation. Based on our previous homology model structure for Gc from Andes hantavirus (ANDV), here we predicted and generated recombinant DIII and stem peptides to test whether these fragments inhibit hantavirus membrane fusion and cell entry. Recombinant ANDV DIII was soluble, presented disulfide bridges and beta-sheet secondary structure, supporting the in silico model. Using DIII and the C-terminal part of the stem region, the infection of cells by ANDV was blocked up to 60% when fusion of ANDV occurred within the endosomal route, and up to 95% when fusion occurred with the plasma membrane. Furthermore, the fragments impaired ANDV glycoprotein-mediated cell-cell fusion, and cross-inhibited the fusion mediated by the glycoproteins from Puumala virus (PUUV). The Gc fragments interfered in ANDV cell entry by preventing membrane hemifusion and pore formation, retaining Gc in a non-resistant homotrimer stage, as described for DIII and stem peptide inhibitors of class II fusion proteins. Collectively, our results demonstrate that hantavirus Gc shares not only structural, but also mechanistic similarity with class II viral fusion proteins, and will hopefully help in developing novel therapeutic strategies against hantaviruses.",2016 Jul 14,"['Barriga, Gonzalo P.', 'Villalón-Letelier, Fernando', 'Márquez, Chantal L.', 'Bignon, Eduardo A.', 'Acuña, Rodrigo', 'Ross, Breyan H.', 'Monasterio, Octavio', 'Mardones, Gonzalo A.', 'Vidal, Simon E.', 'Tischler, Nicole D.']",PLoS Negl Trop Dis,,,True
ff6ee9512267f847d91a0185e794ac98f15fe5d0,PMC,An In Vivo Selection Identifies Listeria monocytogenes Genes Required to Sense the Intracellular Environment and Activate Virulence Factor Expression,http://dx.doi.org/10.1371/journal.ppat.1005741,PMC4945081,27414028,CC BY,"Listeria monocytogenes is an environmental saprophyte and facultative intracellular bacterial pathogen with a well-defined life-cycle that involves escape from a phagosome, rapid cytosolic growth, and ActA-dependent cell-to-cell spread, all of which are dependent on the master transcriptional regulator PrfA. The environmental cues that lead to temporal and spatial control of L. monocytogenes virulence gene expression are poorly understood. In this study, we took advantage of the robust up-regulation of ActA that occurs intracellularly and expressed Cre recombinase from the actA promoter and 5’ untranslated region in a strain in which loxP sites flanked essential genes, so that activation of actA led to bacterial death. Upon screening for transposon mutants that survived intracellularly, six genes were identified as necessary for ActA expression. Strikingly, most of the genes, including gshF, spxA1, yjbH, and ohrA, are predicted to play important roles in bacterial redox regulation. The mutants identified in the genetic selection fell into three broad categories: (1) those that failed to reach the cytosolic compartment; (2) mutants that entered the cytosol, but failed to activate the master virulence regulator PrfA; and (3) mutants that entered the cytosol and activated transcription of actA, but failed to synthesize it. The identification of mutants defective in vacuolar escape suggests that up-regulation of ActA occurs in the host cytosol and not the vacuole. Moreover, these results provide evidence for two non-redundant cytosolic cues; the first results in allosteric activation of PrfA via increased glutathione levels and transcriptional activation of actA while the second results in translational activation of actA and requires yjbH. Although the precise host cues have not yet been identified, we suggest that intracellular redox stress occurs as a consequence of both host and pathogen remodeling their metabolism upon infection.",2016 Jul 14,"['Reniere, Michelle L.', 'Whiteley, Aaron T.', 'Portnoy, Daniel A.']",PLoS Pathog,,,True
8f14ee043acb5f880df53ebdd12d6edc71ddb851,PMC,Community ‐and hospital laboratory‐based surveillance for respiratory viruses,http://dx.doi.org/10.1111/irv.12387,PMC4947942,26987664,CC BY,"Traditional surveillance for respiratory viruses relies on symptom detection and laboratory detection during medically attended encounters for acute respiratory infection/influenza‐like illness (ARI/ILI). Ecological momentary reporting using text messages is a novel method for surveillance. This study compares respiratory viral activity detected through longitudinal community‐based surveillance using text message responses for sample acquisition and testing to respiratory viral activity obtained from hospital laboratory data from the same community. We demonstrate a significant correlation between community‐ and hospital laboratory‐based surveillance for most respiratory viruses, although the relative proportions of viruses detected in the community and hospital differed significantly.",2016 Sep 27,"['Zachariah, Philip', 'Whittier, Susan', 'Reed, Carrie', 'LaRussa, Philip', 'Larson, Elaine L.', 'Vargas, Celibell Y.', 'Saiman, Lisa', 'Stockwell, Melissa S.']",Influenza Other Respir Viruses,,,True
a3ff62cdc7cd33bb6618950b28fe649bf95ef6de,PMC,"Type‐specific clinical characteristics of adenovirus‐associated influenza‐like illness at five US military medical centers, 2009–2014",http://dx.doi.org/10.1111/irv.12392,PMC4947946,27062998,CC BY,"BACKGROUND: Adenovirus is a recognized cause of influenza‐like illness (ILI). The proportion of ILI attributable to adenovirus is not known. Moreover, knowledge gaps remain with respect to the epidemiologic, virologic, and clinical characteristics of adenovirus‐associated ILI among otherwise healthy individuals. METHODS: An observational, longitudinal study of <65‐year‐old patients with febrile ILI at five medical centers was conducted from 2009 to 2014. Nasopharyngeal specimens obtained at enrollment were first tested by single‐reaction PCR for adenovirus, then further evaluated by a multiplex PCR assay for other respiratory viral pathogens. Symptoms over a 28‐day period were collected. RESULTS: We enrolled 1536 individuals, among whom 43 (2·8%) were positive for adenovirus. The median age of cases was 3·4 years (range: 4 months to 41 years). Three were hospitalized. Species and serotype information was available for 33 (76·7%) cases. Species C (n = 21) was the most common, followed by B3 (n = 9) and one each of E4a, D46, and A. Species C infections were more frequent in children (P < 0·01). Half of the cases were positive for at least one other respiratory viral pathogen. Symptoms were generally mild and most commonly included cough (90%), fatigue (79%), rhinorrhea (74%), loss of appetite (71%), and sore throat (64%). Children with non‐C adenovirus infection were more likely to report sore throat (P = 0·05) and hoarseness (P = 0·06) than those with species C infection. CONCLUSIONS: Adenovirus is frequently detected with other respiratory viruses. Persons with non‐C adenovirus infections reported more severe symptoms, suggesting there may be species‐specific differences in virulence and/or host response to infection.",2016 Sep 13,"['Koren, Michael A.', 'Arnold, John C.', 'Fairchok, Mary P.', 'Lalani, Tahaniyat', 'Danaher, Patrick J.', 'Schofield, Christina M.', 'Rajnik, Michael', 'Hansen, Erin A.', 'Mor, Deepika', 'Chen, Wei‐Ju', 'Ridoré, Michelande', 'Burgess, Timothy H.', 'Millar, Eugene V.']",Influenza Other Respir Viruses,,,True
3a8c6a1683a063b6fc3c1bd689ff9c1b83723b4e,PMC,"Viral etiology of severe acute respiratory infections in hospitalized children in Cameroon, 2011–2013",http://dx.doi.org/10.1111/irv.12391,PMC4947949,27012372,CC BY,"BACKGROUND: Severe acute respiratory illness (SARI) is recognized as an important cause of morbidity, mortality, and hospitalization among children in developing countries. Little is known, however, in tropical countries like Cameroon about the cause and seasonality of respiratory infections, especially in hospitalized settings. Objectives: Our study investigates the viral etiology and seasonality of SARI in hospitalized children in Yaounde, Cameroon. METHODS: Prospective clinic surveillance was conducted to identify hospitalized children aged ≤15 years presenting with respiratory symptoms ≤5‐day duration. Demographic and clinical data, and respiratory specimens were collected. Nasopharyngeal samples were tested for 17 respiratory viruses using a multiplex polymerase chain reaction. The viral distribution and demographic data were statistically analyzed. RESULTS: From September 2011 through September 2013, 347 children aged ≤15 years were enrolled. At least one virus was identified in each of 65·4% children, of which 29·5% were coinfections; 27·3% were positive for human adenovirus (hAdV), 13·2% for human respiratory syncytial virus (hRSV), 11·5% for rhinovirus/enterovirus (RV/EV), 10·6% for human bocavirus (hBoV), 9·8% for influenza virus (Inf), 6·6% for human parainfluenza virus (hPIV), 5·7% for human coronavirus (hCoV), and 2·3% for human metapneumovirus (hMPV). While hRSV showed seasonal patterns, hAdV and RV/EV were detected throughout the year and no evident temporal patterns were observed for the remaining viruses. CONCLUSION: Respiratory viruses were associated with a high burden of hospitalizations among children in Cameroon. Nevertheless, additional studies evaluating asymptomatic Cameroonian children will be important in understanding the relationship between viral carriage and disease.",2016 Sep 9,"['Kenmoe, Sebastien', 'Tchendjou, Patrice', 'Vernet, Marie‐Astrid', 'Moyo‐Tetang, Suzie', 'Mossus, Tatiana', 'Njankouo‐Ripa, Mohamadou', 'Kenne, Angeladine', 'Penlap Beng, Véronique', 'Vabret, Astrid', 'Njouom, Richard']",Influenza Other Respir Viruses,,,True
96cd80ad6f658fdc8b0d5e8ce4e1eb1f1daa87f5,PMC,The effect of herd formation among healthcare investors on health sector growth in China,http://dx.doi.org/10.1186/s12939-016-0393-x,PMC4950590,27436298,CC BY,"BACKGROUND: China has become the world‘s second largest healthcare market based on a recent report by the World Health Organization. Eventhough China achieved universal health insurance coverage in 2011, representing the largest expansion of insurance coverage in human history achieved; health inequality remains endemic in China. Lessons from the effect of market crisis on health equity in Europe and other places has reignited interest in exploring the potential healthcare market aberrations that can trigger distributive injustice in healthcare resource allocation among China’s provinces. Recently, many healthcare investors in China have become more concerned about capital preservation, and are responding by abandoning long term investments strategies in healthcare. This investment withdrawal en mass is perceived to be influenced by herding tendencies and can trigger or consolidate endemic health inequality. METHODS: Our study simultaneously employs four testing models (two state spaced models and two return dispersion models) to establish the existence of procyclical (herding) behavior among the stocks and its health equity implications. These are applied to a large set of data to compare and contrast results of herd formation among investors in fourteen healthcare sectors in China. RESULTS: The study reveals that apart from the cross sectional standard deviation (CSSD) model, the remaining two models and our augmented state space model yields significant evidence of herding in all subsectors of the healthcare market. We also find that the herding effect is more prominent during down movements of the market. CONCLUSION: Herding behavior may lead to contemporaneous loss of investor confidence and capital withdrawal and thereby deprive the healthcare sector of the much needed capital for expansion. Thus there may be obvious delay in efforts to bridge the gap in access to healthcare facilities, medical support services, medical supplies, pharmaceuticals, biotechnology, diagnostic substances, medical laboratory and advanced medical equipment across China. Moreover, a potential crash in the healthcare market is possible in the healthcare sector as a result of persistent herding tendencies among investors and that may have more damaging consequences for health inequality in China.",2016 Jul 19,"['Lulin, Zhou', 'Antwi, Henry Asante', 'Wang, Wenxin', 'Yiranbon, Ethel', 'Marfo, Emmanuel Opoku', 'Acheampong, Patrick']",Int J Equity Health,,,True
1b050ba5ac020c50042f89a5f4936404ab2f507f,PMC,Heterogeneity in District-Level Transmission of Ebola Virus Disease during the 2013-2015 Epidemic in West Africa,http://dx.doi.org/10.1371/journal.pntd.0004867,PMC4951043,27434164,CC BY,"The Ebola virus disease (EVD) epidemic in West Africa in 2013–2015 spread heterogeneously across the three hardest-hit countries Guinea, Liberia and Sierra Leone and the estimation of national transmission of EVD provides little information about local dynamics. To investigate district-level transmissibility of EVD, we applied a statistical modelling approach to estimate the basic reproduction number (R(0)) for each affected district and each country using weekly incident case numbers. We estimated growth rates during the early exponential phase of the outbreak using exponential regression of the case counts on the first eight weeks since onset. To take into account the heterogeneity between and within countries, we fitted a mixed effects model and calculated R(0) based on the predicted individual growth rates and the reported serial interval distribution. At district level, R(0) ranged from 0.36 (Dubréka) to 1.72 (Beyla) in Guinea, from 0.53 (Maryland) to 3.37 (Margibi) in Liberia and from 1.14 (Koinadugu) to 2.73 (Western Rural) in Sierra Leone. At national level, we estimated an R(0) of 0.97 (95% CI 0.77–1.18) for Guinea, 1.26 (95% CI 0.98–1.55) for Liberia and 1.66 (95% CI 1.32–2.00) for Sierra Leone. Socio-demographic variables related to urbanisation such as high population density and high wealth index were found positively associated with R(0) suggesting that the consequences of fast urban growth in West Africa may have contributed to the increased spread of EVD.",2016 Jul 19,"['Krauer, Fabienne', 'Gsteiger, Sandro', 'Low, Nicola', 'Hansen, Christian H.', 'Althaus, Christian L.']",PLoS Negl Trop Dis,,,True
6e2133224869e531889ce6d7c7cb0729e4f2c2c6,PMC,Heterogeneity in District-Level Transmission of Ebola Virus Disease during the 2013-2015 Epidemic in West Africa,http://dx.doi.org/10.1371/journal.pntd.0004867,PMC4951043,27434164,CC BY,"The Ebola virus disease (EVD) epidemic in West Africa in 2013–2015 spread heterogeneously across the three hardest-hit countries Guinea, Liberia and Sierra Leone and the estimation of national transmission of EVD provides little information about local dynamics. To investigate district-level transmissibility of EVD, we applied a statistical modelling approach to estimate the basic reproduction number (R(0)) for each affected district and each country using weekly incident case numbers. We estimated growth rates during the early exponential phase of the outbreak using exponential regression of the case counts on the first eight weeks since onset. To take into account the heterogeneity between and within countries, we fitted a mixed effects model and calculated R(0) based on the predicted individual growth rates and the reported serial interval distribution. At district level, R(0) ranged from 0.36 (Dubréka) to 1.72 (Beyla) in Guinea, from 0.53 (Maryland) to 3.37 (Margibi) in Liberia and from 1.14 (Koinadugu) to 2.73 (Western Rural) in Sierra Leone. At national level, we estimated an R(0) of 0.97 (95% CI 0.77–1.18) for Guinea, 1.26 (95% CI 0.98–1.55) for Liberia and 1.66 (95% CI 1.32–2.00) for Sierra Leone. Socio-demographic variables related to urbanisation such as high population density and high wealth index were found positively associated with R(0) suggesting that the consequences of fast urban growth in West Africa may have contributed to the increased spread of EVD.",2016 Jul 19,"['Krauer, Fabienne', 'Gsteiger, Sandro', 'Low, Nicola', 'Hansen, Christian H.', 'Althaus, Christian L.']",PLoS Negl Trop Dis,,,False
e6b79340345095e1d161ff41e5258d1c1d1009e0,PMC,Heterogeneity in District-Level Transmission of Ebola Virus Disease during the 2013-2015 Epidemic in West Africa,http://dx.doi.org/10.1371/journal.pntd.0004867,PMC4951043,27434164,CC BY,"The Ebola virus disease (EVD) epidemic in West Africa in 2013–2015 spread heterogeneously across the three hardest-hit countries Guinea, Liberia and Sierra Leone and the estimation of national transmission of EVD provides little information about local dynamics. To investigate district-level transmissibility of EVD, we applied a statistical modelling approach to estimate the basic reproduction number (R(0)) for each affected district and each country using weekly incident case numbers. We estimated growth rates during the early exponential phase of the outbreak using exponential regression of the case counts on the first eight weeks since onset. To take into account the heterogeneity between and within countries, we fitted a mixed effects model and calculated R(0) based on the predicted individual growth rates and the reported serial interval distribution. At district level, R(0) ranged from 0.36 (Dubréka) to 1.72 (Beyla) in Guinea, from 0.53 (Maryland) to 3.37 (Margibi) in Liberia and from 1.14 (Koinadugu) to 2.73 (Western Rural) in Sierra Leone. At national level, we estimated an R(0) of 0.97 (95% CI 0.77–1.18) for Guinea, 1.26 (95% CI 0.98–1.55) for Liberia and 1.66 (95% CI 1.32–2.00) for Sierra Leone. Socio-demographic variables related to urbanisation such as high population density and high wealth index were found positively associated with R(0) suggesting that the consequences of fast urban growth in West Africa may have contributed to the increased spread of EVD.",2016 Jul 19,"['Krauer, Fabienne', 'Gsteiger, Sandro', 'Low, Nicola', 'Hansen, Christian H.', 'Althaus, Christian L.']",PLoS Negl Trop Dis,,,False
58383a13c8f80823bd6cf3516faf38c1687994a7,PMC,Heterogeneity in District-Level Transmission of Ebola Virus Disease during the 2013-2015 Epidemic in West Africa,http://dx.doi.org/10.1371/journal.pntd.0004867,PMC4951043,27434164,CC BY,"The Ebola virus disease (EVD) epidemic in West Africa in 2013–2015 spread heterogeneously across the three hardest-hit countries Guinea, Liberia and Sierra Leone and the estimation of national transmission of EVD provides little information about local dynamics. To investigate district-level transmissibility of EVD, we applied a statistical modelling approach to estimate the basic reproduction number (R(0)) for each affected district and each country using weekly incident case numbers. We estimated growth rates during the early exponential phase of the outbreak using exponential regression of the case counts on the first eight weeks since onset. To take into account the heterogeneity between and within countries, we fitted a mixed effects model and calculated R(0) based on the predicted individual growth rates and the reported serial interval distribution. At district level, R(0) ranged from 0.36 (Dubréka) to 1.72 (Beyla) in Guinea, from 0.53 (Maryland) to 3.37 (Margibi) in Liberia and from 1.14 (Koinadugu) to 2.73 (Western Rural) in Sierra Leone. At national level, we estimated an R(0) of 0.97 (95% CI 0.77–1.18) for Guinea, 1.26 (95% CI 0.98–1.55) for Liberia and 1.66 (95% CI 1.32–2.00) for Sierra Leone. Socio-demographic variables related to urbanisation such as high population density and high wealth index were found positively associated with R(0) suggesting that the consequences of fast urban growth in West Africa may have contributed to the increased spread of EVD.",2016 Jul 19,"['Krauer, Fabienne', 'Gsteiger, Sandro', 'Low, Nicola', 'Hansen, Christian H.', 'Althaus, Christian L.']",PLoS Negl Trop Dis,,,True
e0f39f2d61d66f276287f181454ae85cdafb7ffa,PMC,Respiratory Virus Detection and Clinical Diagnosis in Children Attending Day Care,http://dx.doi.org/10.1371/journal.pone.0159196,PMC4951077,27433803,CC BY,"BACKGROUND: Respiratory viruses often have been studied in children with respiratory tract infection (RTI), but less knowledge exists about viruses in asymptomatic children. We have studied the occurrence of a broad panel of respiratory viruses in apparently healthy children attending day care, taking into account the influence of possible confounding factors, such as age, clinical signs of respiratory tract infection (RTI), location (day-care section) and season. METHODS: We have studied 161 children in two day-care centers, each with separate sections for younger and older children, during four autumn and winter visits over a two-year period. A total of 355 clinical examinations were performed, and 343 nasopharyngeal samples (NPS) were analyzed by semi-quantitative, real-time, polymerase chain reaction (PCR) tests for 19 respiratory pathogens. RESULT: Forty-three percent of all NPS were PCR-positive for ≥ 1 of 13 virus species, with high species variation during visits. Rhinovirus 26% (88/343 NPS), enterovirus 12% (40/343) and parechovirus 9% (30/343) were detected in every visit, and the rates varied in relation to age, day-care section and season. Ten other viruses were detected in ≤ 3% of the NPS. Generally, viruses occurred together in the NPS. In 24% (79/331) of the clinical examinations with available NPS, the children had clear signs of RTI, while in 41% (135/331) they had mild signs, and in 35% (117/331) the children had no signs of RTI. Moreover, viruses were found in 70% (55/79) of children with clear signs of RTI, in 41% (55/135) with mild signs and in 30% (35/117) without any signs of RTI (p < 0.001). CONCLUSIONS: Positive PCR tests for respiratory viruses, particularly picornaviruses, were frequently detected in apparently healthy children attending day care. Virus detection rates were related to age, presence of clinical signs of RTI, location in day care and season.",2016 Jul 19,"['Moe, Nina', 'Pedersen, Bård', 'Nordbø, Svein Arne', 'Skanke, Lars Høsøien', 'Krokstad, Sidsel', 'Smyrnaios, Anastasios', 'Døllner, Henrik']",PLoS One,,,True
04299cd1ecb45c984de64da12daf3ccc1fe2abe2,PMC,Intestinal microbiota and chronic constipation,http://dx.doi.org/10.1186/s40064-016-2821-1,PMC4951383,27478747,CC BY,"Chronic constipation is a prevalent, burdensome gastrointestinal disorder whose aetiology and pathophysiology remains poorly understood and is most likely multifactorial. Differences in the composition of the intestinal microbiota have been demonstrated when constipated patients and healthy controls have been compared. Growing evidence indicates that alterations of intestinal microbiota may contribute to constipation and constipation-related symptoms. The intestinal microbiota is a collection of microorganisms that live within the gastrointestinal tract, and perform many important health-promoting functions. The intestinal microbiota aids in the breakdown of food products into absorbable nutrients, stimulates the host immune system, prevents growth of pathogenic bacteria and produces a great variety of biologically important compounds. In this review, we will summarize the current evidence supporting roles of the intestinal microbiota in the pathogenesis and management of chronic constipation. The discussion will shed light on the novel mechanisms of intestinal microbiota and gut function interactions, which is invaluable in ultimately developing new therapeutic tools for the treatment of chronic constipation.",2016 Jul 19,"['Zhao, Ying', 'Yu, Yan-Bo']",Springerplus,,,True
a21bd16035d028aae34bab89c3be720ffec176a1,PMC,"Can free open access resources strengthen knowledge-based emerging public health priorities, policies and programs in Africa?",http://dx.doi.org/10.12688/f1000research.8662.1,PMC4955019,27508058,CC BY,"Tackling emerging epidemics and infectious diseases burden in Africa requires increasing unrestricted open access and free use or reuse of regional and global policies reforms as well as timely communication capabilities and strategies. Promoting, scaling up data and information sharing between African researchers and international partners are of vital importance in accelerating open access at no cost. Free Open Access (FOA) health data and information acceptability, uptake tactics and sustainable mechanisms are urgently needed. These are critical in establishing real time and effective knowledge or evidence-based translation, proven and validated approaches, strategies and tools to strengthen and revamp health systems.  As such, early and timely access to needed emerging public health information is meant to be instrumental and valuable for policy-makers, implementers, care providers, researchers, health-related institutions and stakeholders including populations when guiding health financing, and planning contextual programs.",2016 May 9,"['Tambo, Ernest', 'Madjou, Ghislaine', 'Khayeka-Wandabwa, Christopher', 'Tekwu, Emmanuel N.', 'Olalubi, Oluwasogo A.', 'Midzi, Nicolas', 'Bengyella, Louis', 'Adedeji, Ahmed A.', 'Ngogang, Jeanne Y.']",F1000Res,,,True
9dc7d12caa315d1608b7e1310aa4ba033d50d8e0,PMC,Airborne biological hazards and urban transport infrastructure: current challenges and future directions,http://dx.doi.org/10.1007/s11356-016-7064-8,PMC4956722,27318484,CC BY,"Exposure to airborne biological hazards in an ever expanding urban transport infrastructure and highly diverse mobile population is of growing concern, in terms of both public health and biosecurity. The existing policies and practices on design, construction and operation of these infrastructures may have severe implications for airborne disease transmission, particularly, in the event of a pandemic or intentional release of biological of agents. This paper reviews existing knowledge on airborne disease transmission in different modes of transport, highlights the factors enhancing the vulnerability of transport infrastructures to airborne disease transmission, discusses the potential protection measures and identifies the research gaps in order to build a bioresilient transport infrastructure. The unification of security and public health research, inclusion of public health security concepts at the design and planning phase, and a holistic system approach involving all the stakeholders over the life cycle of transport infrastructure hold the key to mitigate the challenges posed by biological hazards in the twenty-first century transport infrastructure.",2016 Jun 18,"['Nasir, Zaheer Ahmad', 'Campos, Luiza Cintra', 'Christie, Nicola', 'Colbeck, Ian']",Environ Sci Pollut Res Int,,,True
6a5ec0f5b18ea19bc152ad79a1b72043385a8f3f,PMC,Predicting the international spread of Middle East respiratory syndrome (MERS),http://dx.doi.org/10.1186/s12879-016-1675-z,PMC4957429,27449387,CC BY,"BACKGROUND: The Middle East respiratory syndrome (MERS) associated coronavirus has been imported via travelers into multiple countries around the world. In order to support risk assessment practice, the present study aimed to devise a novel statistical model to quantify the country-level risk of experiencing an importation of MERS case. METHODS: We analyzed the arrival time of each reported MERS importation around the world, i.e., the date on which imported cases entered a specific country, which was modeled as a dependent variable in our analysis. We also used openly accessible data including the airline transportation network to parameterize a hazard-based risk prediction model. The hazard was assumed to follow an inverse function of the effective distance (i.e., the minimum effective length of a path from origin to destination), which was calculated from the airline transportation data, from Saudi Arabia to each country. Both country-specific religion and the incidence data of MERS in Saudi Arabia were used to improve our model prediction. RESULTS: Our estimates of the risk of MERS importation appeared to be right skewed, which facilitated the visual identification of countries at highest risk of MERS importations in the right tail of the distribution. The simplest model that relied solely on the effective distance yielded the best predictive performance (Area under the curve (AUC) = 0.943) with 100 % sensitivity and 79.6 % specificity. Out of the 30 countries estimated to be at highest risk of MERS case importation, 17 countries (56.7 %) have already reported at least one importation of MERS. Although model fit measured by Akaike Information Criterion (AIC) was improved by including country-specific religion (i.e. Muslim majority country), the predictive performance as measured by AUC was not improved after accounting for this covariate. CONCLUSIONS: Our relatively simple statistical model based on the effective distance derived from the airline transportation network data was found to help predicting the risk of importing MERS at the country level. The successful application of the effective distance model to predict MERS importations, particularly when computationally intensive large-scale transmission models may not be immediately applicable could have been benefited from the particularly low transmissibility of the MERS coronavirus.",2016 Jul 22,"['Nah, Kyeongah', 'Otsuki, Shiori', 'Chowell, Gerardo', 'Nishiura, Hiroshi']",BMC Infect Dis,,,True
4a4829a678305f54711666d194597971627c7b48,PMC,Influenza A (H10N7) Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets,http://dx.doi.org/10.1371/journal.pone.0159625,PMC4957826,27448168,CC BY,"Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7) in harbor seals (Phoca vitulina). This epidemic caused high mortality in seals along the north-west coast of Europe and represented a potential risk for human health. To characterize the spectrum of lesions and to identify the target cells and viral distribution, findings in 16 harbor seals spontaneously infected with Seal/H10N7 are described. The seals had respiratory tract inflammation extending from the nasal cavity to bronchi associated with intralesional virus antigen in respiratory epithelial cells. Virus infection was restricted to the respiratory tract. The fatal outcome of the viral infection in seals was most likely caused by secondary bacterial infections. To investigate the pathogenic potential of H10N7 infection for humans, we inoculated the seal virus intratracheally into six ferrets and performed pathological and virological analyses at 3 and 7 days post inoculation. These experimentally inoculated ferrets displayed mild clinical signs, virus excretion from the pharynx and respiratory tract inflammation extending from bronchi to alveoli that was associated with virus antigen expression exclusively in the respiratory epithelium. Virus was isolated only from the respiratory tract. In conclusion, Seal/H10N7 infection in naturally infected harbor seals and experimentally infected ferrets shows that respiratory epithelial cells are the permissive cells for viral replication. Fatal outcome in seals was caused by secondary bacterial pneumonia similar to that in fatal human cases during influenza pandemics. Productive infection of ferrets indicates that seal/H10N7 may possess a zoonotic potential. This outbreak of LPAI from wild birds to seals demonstrates the risk of such occasions for mammals and thus humans.",2016 Jul 22,"['van den Brand, Judith M. A.', 'Wohlsein, Peter', 'Herfst, Sander', 'Bodewes, Rogier', 'Pfankuche, Vanessa M.', 'van de Bildt, Marco W. G.', 'Seehusen, Frauke', 'Puff, Christina', 'Richard, Mathilde', 'Siebert, Ursula', 'Lehnert, Kristina', 'Bestebroer, Theo', 'Lexmond, Pascal', 'Fouchier, Ron A. M.', 'Prenger-Berninghoff, Ellen', 'Herbst, Werner', 'Koopmans, Marion', 'Osterhaus, Albert D. M. E.', 'Kuiken, Thijs', 'Baumgärtner, Wolfgang']",PLoS One,,,True
f17288f985aa9c44a23132028973162a800726f4,PMC,Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins,http://dx.doi.org/10.1128/mBio.00584-16,PMC4958244,27406561,CC BY,"The first step in the infection of humans by microbial pathogens is their adherence to host tissue cells, which is frequently based on the binding of carbohydrate-binding proteins (lectin-like adhesins) to human cell receptors that expose glycans. In only a few cases have the human receptors of pathogenic adhesins been described. A novel strategy—based on the construction of a lectin-glycan interaction (LGI) network—to identify the potential human binding receptors for pathogenic adhesins with lectin activity was developed. The new approach is based on linking glycan array screening results of these adhesins to a human glycoprotein database via the construction of an LGI network. This strategy was used to detect human receptors for virulent Escherichia coli (FimH adhesin), and the fungal pathogens Candida albicans (Als1p and Als3p adhesins) and C. glabrata (Epa1, Epa6, and Epa7 adhesins), which cause candidiasis. This LGI network strategy allows the profiling of potential adhesin binding receptors in the host with prioritization, based on experimental binding data, of the most relevant interactions. New potential targets for the selected adhesins were predicted and experimentally confirmed. This methodology was also used to predict lectin interactions with envelope glycoproteins of human-pathogenic viruses. It was shown that this strategy was successful in revealing that the FimH adhesin has anti-HIV activity.",2016 Jul 12,"['Ielasi, Francesco S.', 'Alioscha-Perez, Mitchel', 'Donohue, Dagmara', 'Claes, Sandra', 'Sahli, Hichem', 'Schols, Dominique', 'Willaert, Ronnie G.']",mBio,,,True
d24a70c5203617db24e9777727d824bcad5597c7,PMC,Identification and characterization of the role of c-terminal Src kinase in dengue virus replication,http://dx.doi.org/10.1038/srep30490,PMC4960526,27457684,CC BY,"We screened a siRNA library targeting human tyrosine kinases in Huh-7 cells and identified c-terminal Src kinase (Csk) as one of the kinases involved in dengue virus replication. Knock-down of Csk expression by siRNAs or inhibition of Csk by an inhibitor reduced dengue virus RNA levels but did not affect viral entry. Csk partially colocalized with viral replication compartments. Dengue infection was drastically reduced in cells lacking the three ubiquitous src family kinases, Src, Fyn and Yes. Csk knock-down in these cells failed to block dengue virus replication suggesting that the effect of Csk is via regulation of Src family kinases. Csk was found to be hyper-phosphorylated during dengue infection and inhibition of protein kinase A led to a block in Csk phosphorylation and dengue virus replication. Overexpression studies suggest an important role for the kinase and SH3 domains in this process. Our results identified a novel role for Csk as a host tyrosine kinase involved in dengue virus replication and provide further insights into the role of host factors in dengue replication.",2016 Jul 26,"['Kumar, Rinki', 'Agrawal, Tanvi', 'Khan, Naseem Ahmed', 'Nakayama, Yuji', 'Medigeshi, Guruprasad R.']",Sci Rep,,,True
013efebeacfb3148ec21bb8d83b040dd0437ea3a,PMC,Identification and characterization of the role of c-terminal Src kinase in dengue virus replication,http://dx.doi.org/10.1038/srep30490,PMC4960526,27457684,CC BY,"We screened a siRNA library targeting human tyrosine kinases in Huh-7 cells and identified c-terminal Src kinase (Csk) as one of the kinases involved in dengue virus replication. Knock-down of Csk expression by siRNAs or inhibition of Csk by an inhibitor reduced dengue virus RNA levels but did not affect viral entry. Csk partially colocalized with viral replication compartments. Dengue infection was drastically reduced in cells lacking the three ubiquitous src family kinases, Src, Fyn and Yes. Csk knock-down in these cells failed to block dengue virus replication suggesting that the effect of Csk is via regulation of Src family kinases. Csk was found to be hyper-phosphorylated during dengue infection and inhibition of protein kinase A led to a block in Csk phosphorylation and dengue virus replication. Overexpression studies suggest an important role for the kinase and SH3 domains in this process. Our results identified a novel role for Csk as a host tyrosine kinase involved in dengue virus replication and provide further insights into the role of host factors in dengue replication.",2016 Jul 26,"['Kumar, Rinki', 'Agrawal, Tanvi', 'Khan, Naseem Ahmed', 'Nakayama, Yuji', 'Medigeshi, Guruprasad R.']",Sci Rep,,,False
50aa5eba3f398675c8f3c53a819aca7fb8b4af33,PMC,Assessing worldwide research activity on probiotics in pediatrics using Scopus database: 1994–2014,http://dx.doi.org/10.1186/s40413-016-0116-1,PMC4960683,27504147,CC BY,"BACKGROUND: A wide variety of probiotic products has been introduced into the market in the past decade. Research trends and activity on probiotics help understand how these products were evolved and their potential future role in medicine. The objective of this study was to assess the research activity on probiotics in pediatrics using bibliometric indicators and network visualization. METHODS: Original and review articles on probiotics in pediatrics published worldwide were retrieved from SciVerse, Scopus (1994–2014) and analyzed. VOSviewer was used for network visualization. RESULTS: The total number of documents published on probiotics in pediatrics was 2817. Research activity on probiotics in pediatrics showed approximately 90- fold increase during the study period. Approximately 22 % of published articles originated from USA and has the greatest share, however, Finland ranked first when data were stratified by population or income. The most productive institution in this field was Turku University in Finland with 82 (2.91 %) articles. Half of the prolific authors were also from Finland. Most of the published research activity appeared in Journal of Pediatric Gastroenterology and Nutrition. Most frequently encountered title terms include nutrition, infant formula, necrotizing enetrocolitis, allergy, and diarrhea. The total number of citations for the retreived documents documents was 70991, and the average citation per article was 25.20. CONCLUSIONS: Interest in probiotic research and its potential benefits in pediatric ailments is relatively recent but significantly increasing. Bibliometric analysis can be used as an indicator of the importance and growth of probiotic use in pediatrics.",2016 Jul 25,"['Sweileh, Waleed M.', 'Shraim, Naser Y.', 'Al-Jabi, Samah W.', 'Sawalha, Ansam F.', 'Rahhal, Belal', 'Khayyat, Rasha A.', 'Zyoud, Sa’ed H.']",World Allergy Organ J,,,True
5b15c62ee761d6eefeb7d2ef023f804bfdc41edc,PMC,Optimal Decision Model for Sustainable Hospital Building Renovation—A Case Study of a Vacant School Building Converting into a Community Public Hospital,http://dx.doi.org/10.3390/ijerph13070630,PMC4962171,27347986,CC BY,"Much attention has been paid to hospitals environments since modern pandemics have emerged. The building sector is considered to be the largest world energy consumer, so many global organizations are attempting to create a sustainable environment in building construction by reducing energy consumption. Therefore, maintaining high standards of hygiene while reducing energy consumption has become a major task for hospitals. This study develops a decision model based on genetic algorithms and A* graph search algorithms to evaluate existing hospital environmental conditions and to recommend an optimal scheme of sustainable renovation strategies, considering trade-offs among minimal renovation cost, maximum quality improvement, and low environmental impact. Reusing vacant buildings is a global and sustainable trend. In Taiwan, for example, more and more school space will be unoccupied due to a rapidly declining birth rate. Integrating medical care with local community elder-care efforts becomes important because of the aging population. This research introduces a model that converts a simulated vacant school building into a community public hospital renovation project in order to validate the solutions made by hospital managers and suggested by the system. The result reveals that the system performs well and its solutions are more successful than the actions undertaken by decision-makers. This system can improve traditional hospital building condition assessment while making it more effective and efficient.",2016 Jul 24,"['Juan, Yi-Kai', 'Cheng, Yu-Ching', 'Perng, Yeng-Horng', 'Castro-Lacouture, Daniel']",Int J Environ Res Public Health,,,True
c6e40c6e9f16528e3a7495481311cff9a886d86e,PMC,Sounding the Alarm: Health in the Anthropocene,http://dx.doi.org/10.3390/ijerph13070665,PMC4962206,27376314,CC BY,"There is growing scientific and public recognition that human actions, directly and indirectly, have profoundly changed the Earth system, in a still accelerating process, increasingly called the “Anthropocene”. Planetary transformation, including of the atmosphere, climate, ecosystems and biodiversity, has enormous implications for human health, many of which are deeply disturbing, especially in low-income settings. A few health consequences of the Anthropocene have been partially recognized, including within environmental epidemiology, but their long-term consequences remain poorly understood and greatly under-rated. For example Syria could be a “sentinel” population, giving a glimpse to a much wider dystopian future. Health-Earth is a research network, co-founded in 2014, which seeks, with other groups, to catalyse a powerful curative response by the wider health community. This paper builds on a symposium presented by Health-Earth members at the 2015 conference of the International Society for Environmental Epidemiology. It reviews and synthesizes parts of the large literature relevant to the interaction between the changing Earth system and human health. It concludes that this topic should be prominent within future environmental epidemiology and public health. Created by our species, these challenges may be soluble, but solutions require far more understanding and resources than are currently being made available.",2016 Jul 30,"Butler, Colin D.",Int J Environ Res Public Health,,,True
bf0bd7e3007cf87a4907ecf1bbf819d28e5c3c63,PMC,Structure-Based Design of Head-Only Fusion Glycoprotein Immunogens for Respiratory Syncytial Virus,http://dx.doi.org/10.1371/journal.pone.0159709,PMC4963090,27463224,CC0,"Respiratory syncytial virus (RSV) is a significant cause of severe respiratory illness worldwide, particularly in infants, young children, and the elderly. Although no licensed vaccine is currently available, an engineered version of the metastable RSV fusion (F) surface glycoprotein—stabilized in the pre-fusion (pre-F) conformation by “DS-Cav1” mutations—elicits high titer RSV-neutralizing responses. Moreover, pre-F-specific antibodies, often against the neutralization-sensitive antigenic site Ø in the membrane-distal head region of trimeric F glycoprotein, comprise a substantial portion of the human response to natural RSV infection. To focus the vaccine-elicited response to antigenic site Ø, we designed a series of RSV F immunogens that comprised the membrane-distal head of the F glycoprotein in its pre-F conformation. These “head-only” immunogens formed monomers, dimers, and trimers. Antigenic analysis revealed that a majority of the 70 engineered head-only immunogens displayed reactivity to site Ø-targeting antibodies, which was similar to that of the parent RSV F DS-Cav1 trimers, often with increased thermostability. We evaluated four of these head-only immunogens in detail, probing their recognition by antibodies, their physical stability, structure, and immunogenicity. When tested in naïve mice, a head-only trimer, half the size of the parent RSV F trimer, induced RSV titers, which were statistically comparable to those induced by DS-Cav1. When used to boost DS-Cav1-primed mice, two head-only RSV F immunogens, a dimer and a trimer, boosted RSV-neutralizing titers to levels that were comparable to those boosted by DS-Cav1, although with higher site Ø-directed responses. Our results provide proof-of-concept for the ability of the smaller head-only RSV F immunogens to focus the vaccine-elicited response to antigenic site Ø. Decent primary immunogenicity, enhanced physical stability, potential ease of manufacture, and potent immunogenicity upon boosting suggest these head-only RSV F immunogens, engineered to retain the pre-fusion conformation, may have advantages as candidate RSV vaccines.",2016 Jul 27,"['Boyington, Jeffrey C.', 'Joyce, M. Gordon', 'Sastry, Mallika', 'Stewart-Jones, Guillaume B. E.', 'Chen, Man', 'Kong, Wing-Pui', 'Ngwuta, Joan O.', 'Thomas, Paul V.', 'Tsybovsky, Yaroslav', 'Yang, Yongping', 'Zhang, Baoshan', 'Chen, Lei', 'Druz, Aliaksandr', 'Georgiev, Ivelin S.', 'Ko, Kiyoon', 'Zhou, Tongqing', 'Mascola, John R.', 'Graham, Barney S.', 'Kwong, Peter D.']",PLoS One,,,True
f8a4ffd24e2b938c844b4affc6d03ffe51f0ff16,PMC,Structure-Based Design of Head-Only Fusion Glycoprotein Immunogens for Respiratory Syncytial Virus,http://dx.doi.org/10.1371/journal.pone.0159709,PMC4963090,27463224,CC0,"Respiratory syncytial virus (RSV) is a significant cause of severe respiratory illness worldwide, particularly in infants, young children, and the elderly. Although no licensed vaccine is currently available, an engineered version of the metastable RSV fusion (F) surface glycoprotein—stabilized in the pre-fusion (pre-F) conformation by “DS-Cav1” mutations—elicits high titer RSV-neutralizing responses. Moreover, pre-F-specific antibodies, often against the neutralization-sensitive antigenic site Ø in the membrane-distal head region of trimeric F glycoprotein, comprise a substantial portion of the human response to natural RSV infection. To focus the vaccine-elicited response to antigenic site Ø, we designed a series of RSV F immunogens that comprised the membrane-distal head of the F glycoprotein in its pre-F conformation. These “head-only” immunogens formed monomers, dimers, and trimers. Antigenic analysis revealed that a majority of the 70 engineered head-only immunogens displayed reactivity to site Ø-targeting antibodies, which was similar to that of the parent RSV F DS-Cav1 trimers, often with increased thermostability. We evaluated four of these head-only immunogens in detail, probing their recognition by antibodies, their physical stability, structure, and immunogenicity. When tested in naïve mice, a head-only trimer, half the size of the parent RSV F trimer, induced RSV titers, which were statistically comparable to those induced by DS-Cav1. When used to boost DS-Cav1-primed mice, two head-only RSV F immunogens, a dimer and a trimer, boosted RSV-neutralizing titers to levels that were comparable to those boosted by DS-Cav1, although with higher site Ø-directed responses. Our results provide proof-of-concept for the ability of the smaller head-only RSV F immunogens to focus the vaccine-elicited response to antigenic site Ø. Decent primary immunogenicity, enhanced physical stability, potential ease of manufacture, and potent immunogenicity upon boosting suggest these head-only RSV F immunogens, engineered to retain the pre-fusion conformation, may have advantages as candidate RSV vaccines.",2016 Jul 27,"['Boyington, Jeffrey C.', 'Joyce, M. Gordon', 'Sastry, Mallika', 'Stewart-Jones, Guillaume B. E.', 'Chen, Man', 'Kong, Wing-Pui', 'Ngwuta, Joan O.', 'Thomas, Paul V.', 'Tsybovsky, Yaroslav', 'Yang, Yongping', 'Zhang, Baoshan', 'Chen, Lei', 'Druz, Aliaksandr', 'Georgiev, Ivelin S.', 'Ko, Kiyoon', 'Zhou, Tongqing', 'Mascola, John R.', 'Graham, Barney S.', 'Kwong, Peter D.']",PLoS One,,,False
a48482a6bd5e78f140777702151cffe852ea5f1e,PMC,Genome-Wide Analysis of Codon Usage Bias in Epichloë festucae,http://dx.doi.org/10.3390/ijms17071138,PMC4964511,27428961,CC BY,"Analysis of codon usage data has both practical and theoretical applications in understanding the basics of molecular biology. Differences in codon usage patterns among genes reflect variations in local base compositional biases and the intensity of natural selection. Recently, there have been several reports related to codon usage in fungi, but little is known about codon usage bias in Epichloë endophytes. The present study aimed to assess codon usage patterns and biases in 4870 sequences from Epichloë festucae, which may be helpful in revealing the constraint factors such as mutation or selection pressure and improving the bioreactor on the cloning, expression, and characterization of some special genes. The GC content with 56.41% is higher than the AT content (43.59%) in E. festucae. The results of neutrality and effective number of codons plot analyses showed that both mutational bias and natural selection play roles in shaping codon usage in this species. We found that gene length is strongly correlated with codon usage and may contribute to the codon usage patterns observed in genes. Nucleotide composition and gene expression levels also shape codon usage bias in E. festucae. E. festucae exhibits codon usage bias based on the relative synonymous codon usage (RSCU) values of 61 sense codons, with 25 codons showing an RSCU larger than 1. In addition, we identified 27 optimal codons that end in a G or C.",2016 Jul 15,"['Li, Xiuzhang', 'Song, Hui', 'Kuang, Yu', 'Chen, Shuihong', 'Tian, Pei', 'Li, Chunjie', 'Nan, Zhibiao']",Int J Mol Sci,,,True
c1cd72dfc8c71714d7751a0b9820f8f8e0ee3756,PMC,Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses,http://dx.doi.org/10.1074/jbc.M116.736660,PMC4965583,27288409,CC BY,"To determine the effectiveness of immunization strategies used in therapeutic antibody or vaccine development, it is critical to assess the quality of immunization-induced polyclonal antibody responses. Here, we developed a workflow that uses sensitive methods to quantitatively and qualitatively assess immune responses against foreign antigens with regard to antibody binding affinity and epitope diversity. The application of such detailed assessments throughout an immunization campaign can significantly reduce the resources required to generate highly specific antibodies. Our workflow consists of the following two steps: 1) the use of surface plasmon resonance to quantify antigen-specific antibodies and evaluate their apparent binding affinities, and 2) the recovery of serum IgGs using an automated small scale purification system, followed by the determination of their epitope diversity using hydrogen deuterium exchange coupled with mass spectrometry. We showed that these methods were sensitive enough to detect antigen-specific IgGs in the nanogram/μl range and that they provided information for differentiating the antibody responses of the various immunized animals that could not be obtained by conventional methods. We also showed that this workflow can guide the selection of an animal that produces high affinity antibodies with a desired epitope coverage profile, resulting in the generation of potential therapeutic monoclonal antibody clones with desirable functional profiles. We postulate that this workflow will be an important tool in the development of effective vaccines to combat the highly sophisticated evasion mechanisms of pathogens.",2016 Jul 29,"['Yang, Danlin', 'Frego, Lee', 'Lasaro, Marcio', 'Truncali, Kristopher', 'Kroe-Barrett, Rachel', 'Singh, Sanjaya']",J Biol Chem,,,True
a52fd1386e8a463e46bde0e66125bfd826a64f56,PMC,Ebola virus disease and critical illness,http://dx.doi.org/10.1186/s13054-016-1325-2,PMC4965892,27468829,CC BY,"As of 20 May 2016 there have been 28,646 cases and 11,323 deaths resulting from the West African Ebola virus disease (EVD) outbreak reported to the World Health Organization. There continue to be sporadic flare-ups of EVD cases in West Africa. EVD presentation is nonspecific and characterized initially by onset of fatigue, myalgias, arthralgias, headache, and fever; this is followed several days later by anorexia, nausea, vomiting, diarrhea, and abdominal pain. Anorexia and gastrointestinal losses lead to dehydration, electrolyte abnormalities, and metabolic acidosis, and, in some patients, acute kidney injury. Hypoxia and ventilation failure occurs most often with severe illness and may be exacerbated by substantial fluid requirements for intravascular volume repletion and some degree of systemic capillary leak. Although minor bleeding manifestations are common, hypovolemic and septic shock complicated by multisystem organ dysfunction appear the most frequent causes of death. Males and females have been equally affected, with children (0–14 years of age) accounting for 19 %, young adults (15–44 years) 58 %, and older adults (≥45 years) 23 % of reported cases. While the current case fatality proportion in West Africa is approximately 40 %, it has varied substantially over time (highest near the outbreak onset) according to available resources (40–90 % mortality in West Africa compared to under 20 % in Western Europe and the USA), by age (near universal among neonates and high among older adults), and by Ebola viral load at admission. While there is no Ebola virus-specific therapy proven to be effective in clinical trials, mortality has been dramatically lower among EVD patients managed with supportive intensive care in highly resourced settings, allowing for the avoidance of hypovolemia, correction of electrolyte and metabolic abnormalities, and the provision of oxygen, ventilation, vasopressors, and dialysis when indicated. This experience emphasizes that, in addition to evaluating specific medical treatments, improving the global capacity to provide supportive critical care to patients with EVD may be the greatest opportunity to improve patient outcomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1325-2) contains supplementary material, which is available to authorized users.",2016 Jul 29,"['Leligdowicz, Aleksandra', 'Fischer, William A.', 'Uyeki, Timothy M.', 'Fletcher, Thomas E.', 'Adhikari, Neill K. J.', 'Portella, Gina', 'Lamontagne, Francois', 'Clement, Christophe', 'Jacob, Shevin T.', 'Rubinson, Lewis', 'Vanderschuren, Abel', 'Hajek, Jan', 'Murthy, Srinivas', 'Ferri, Mauricio', 'Crozier, Ian', 'Ibrahima, Elhadj', 'Lamah, Marie-Claire', 'Schieffelin, John S.', 'Brett-Major, David', 'Bausch, Daniel G.', 'Shindo, Nikki', 'Chan, Adrienne K.', 'O’Dempsey, Tim', 'Mishra, Sharmistha', 'Jacobs, Michael', 'Dickson, Stuart', 'Lyon, G. Marshall', 'Fowler, Robert A.']",Crit Care,,,True
6b05be390f36231b7e3a06bc30979536eda0ee6e,PMC,Human Rhinovirus B and C Genomes from Rural Coastal Kenya,http://dx.doi.org/10.1128/genomeA.00751-16,PMC4966474,27469941,CC BY,Primer-independent agnostic deep sequencing was used to generate three human rhinovirus (HRV) B genomes and one HRV C genome from samples collected in a household respiratory survey in rural coastal Kenya. The study provides the first rhinovirus genomes from Kenya and will help improve the sensitivity of local molecular diagnostics.,2016 Jul 28,"['Agoti, Charles N.', 'Kiyuka, Patience K.', 'Kamau, Everlyn', 'Munywoki, Patrick K.', 'Bett, Anne', 'van der Hoek, Lia', 'Kellam, Paul', 'Nokes, D. James', 'Cotten, Matthew']",Genome Announc,,,True
ac793b3e925f08bf9fac41b70e5c9a61d1f37e39,PMC,"The Effects of an Online Mind-Body Training Program on Stress, Coping Strategies, Emotional Intelligence, Resilience and Psychological State",http://dx.doi.org/10.1371/journal.pone.0159841,PMC4968838,27479499,CC BY,"The goal of this study was to evaluate the effects of an online mind-body training (MBT) program on participants’ stress, anger, coping strategies, emotional intelligence, resilience, and positive and negative affect. Forty-two healthy women participated in an online MBT program for approximately 8–10 minutes a day for 8 weeks; a control group of 45 healthy women did not participate in the program. Self-report psychological questionnaires were administered before the beginning of the program and at 4 and 8 weeks following its onset. Data from the MBT group and the control group were compared using repeated measures ANOVA and Student’s t-tests. Significant time x group interaction effects were found with respect to stress, coping strategies, anger, emotional intelligence, negative affect and resilience. These results demonstrate beneficial effects of the online MBT program and significant improvements in the psychological capabilities of participants compared with the control group. The effects of online MBT program were similar with those of the previous offline MBT in psychological aspects, suggesting further studies for neuroscientific evidence related stress and emotion of online MBT effects.",2016 Aug 1,"['Jung, Ye-Ha', 'Ha, Tae Min', 'Oh, Chang Young', 'Lee, UI Soon', 'Jang, Joon Hwan', 'Kim, Jungwon', 'Park, Jae-Oh', 'Kang, Do-Hyung']",PLoS One,,,True
19e45f3e51ee8f9151f7f3e901b2a579366abfd0,PMC,Zika Virus: Where Is the Treatment?,http://dx.doi.org/10.1007/s40506-016-0083-7,PMC4969322,27547128,CC BY,,2016 Jul 8,"['Mumtaz, Noreen', 'van Kampen, Jeroen J. A.', 'Reusken, Chantal B. E. M.', 'Boucher, Charles A. B.', 'Koopmans, Marion P. G.']",Curr Treat Options Infect Dis,,,True
fc151568de57c0456578757131c3b49b86286b3c,PMC,"Inhibition of RNA Helicases of ssRNA(+) Virus Belonging to Flaviviridae, Coronaviridae and Picornaviridae Families",http://dx.doi.org/10.1155/2011/213135,PMC4970650,27516903,CC BY,"Many viral pathogens encode the motor proteins named RNA helicases which display various functions in genome replication. General strategies to design specific and selective drugs targeting helicase for the treatment of viral infections could act via one or more of the following mechanisms: inhibition of the NTPase activity, by interferences with ATP binding and therefore by limiting the energy required for the unwinding and translocation, or by allosteric mechanism and therefore by stabilizing the conformation of the enzyme in low helicase activity state; inhibition of nucleic acids binding to the helicase; inhibition of coupling of ATP hydrolysis to unwinding; inhibition of unwinding by sterically blocking helicase translocation. Recently, by in vitro screening studies, it has been reported that several benzotriazole, imidazole, imidazodiazepine, phenothiazine, quinoline, anthracycline, triphenylmethane, tropolone, pyrrole, acridone, small peptide, and Bananin derivatives are endowed with helicase inhibition of pathogen viruses belonging to Flaviviridae, Coronaviridae, and Picornaviridae families.",2011 Nov 14,"['Briguglio, Irene', 'Piras, Sandra', 'Corona, Paola', 'Carta, Antonio']",Int J Med Chem,,,True
6a0f2ecf39a72ca6067517375a485d98b308e2aa,PMC,Pains and Gains from China's Experiences with Emerging Epidemics: From SARS to H7N9,http://dx.doi.org/10.1155/2016/5717108,PMC4971293,27525272,CC BY,"Over the recent decades, China experienced several emerging virus outbreaks including those caused by the severe acute respiratory syndrome- (SARS-) coronavirus (Cov), H5N1 virus, and H7N9 virus. The SARS tragedy revealed faults in China's infectious disease prevention system, propelling the Chinese government to enact reforms that enabled better combating of the subsequent H1N1 and H7N9 avian flu epidemics. The system is buttressed by three fundamental, mutually reinforcing components: (1) enduring government administration reforms, including legislation establishing a unified public health emergency management system; (2) prioritized funding for biotechnology and biomedicine industrialization, especially in the areas of pathogen identification, drug production, and the development of vaccines and diagnostics; and (3) increasing investment for public health and establishment of a rapid-response infectious diseases prevention and control system. China is now using its hard-gained experience to support the fight against Ebola in Africa and the Middle East Respiratory Syndrome in its own country.",2016 Jul 20,"['Wei, Pengfei', 'Cai, Zelang', 'Hua, Jinwen', 'Yu, Weijia', 'Chen, Jiajie', 'Kang, Kang', 'Qiu, Congling', 'Ye, Lanlan', 'Hu, Jiayun', 'Ji, Kunmei']",Biomed Res Int,,,True
7c53b0536ccc6dd11ad7de4f55c0baa934f38763,PMC,Astrovirus VA1 identified by next-generation sequencing in a nasopharyngeal specimen of a febrile Tanzanian child with acute respiratory disease of unknown etiology,http://dx.doi.org/10.1038/emi.2016.67,PMC4972905,27381218,CC BY,,2016 Jul 6,"['Cordey, Samuel', 'Brito, Francisco', 'Vu, Diem-Lan', 'Turin, Lara', 'Kilowoko, Mary', 'Kyungu, Esther', 'Genton, Blaise', 'Zdobnov, Evgeny M', ""D'Acremont, Valérie"", 'Kaiser, Laurent']",Emerg Microbes Infect,,,True
17334b138ba80214847f144ebc57ce27ff9c23cf,PMC,Pulmonary melanoma and “crazy paving” patterns in chest images: a case report and literature review,http://dx.doi.org/10.1186/s12885-016-2630-5,PMC4973081,27488496,CC BY,"BACKGROUND: In the lung, melanoma is mostly arranged as patterns of multiple nodules, solitary nodules, or miliary invasions. Very rarely, it also displays a “crazy paving” pattern (also described as a “paving stone,” “flagstone,” or “slabstone” pattern), which is rarer still in discrete bilateral nodules. This pattern is considered to be caused by pulmonary alveolar proteinosis, but its association with various diseases is unclear. CASE PRESENTATION: A 60-year-old man was diagnosed with pulmonary melanoma. Computed tomography revealed discrete bilateral nodules surrounded by a “paving” pattern. A literature review found more than 40 types of diseases that have presented with “paving” patterns in the lung—predominantly pulmonary alveolar proteinosis, viral pneumonia, exogenous lipoid pneumonia, bacterial pneumonia, pulmonary alveolar microlithiasis, interstitial pneumonia, ARDS, squalene aspiration pneumonia, radiation pneumonitis, drug-induced pneumonitis, pulmonary leptospirosis, pulmonary hemorrhage, and pulmonary nocardiosis. CONCLUSIONS: We describe the first case of pulmonary melanoma in the form of discrete bilateral nodules accompanied with a computed tomography paving pattern. Although pulmonary paving patterns are rare, more than 40 diseases reportedly display them; clinicians should consider melanoma of the lung in differential diagnoses for patients who show such a pattern.",2016 Aug 3,"['Feng, Yikuan', 'Zhao, Jianping', 'Yang, Qun', 'Xiong, Weining', 'Zhen, Guohua', 'Xu, Yongjian', 'Zhang, Zhenxiang', 'Zhang, Huilan']",BMC Cancer,,,True
913e8bcf134a8415f7aa9d3285e15e1425a60d26,PMC,Tear biomarkers for keratoconus,http://dx.doi.org/10.1186/s40662-016-0051-9,PMC4973115,27493978,CC BY,"Keratoconus is a progressive corneal thinning, ectatic condition, which affects vision. Recent advances in corneal topography measurements has helped advance proper diagnosis of this condition and increased research and clinical interests in the disease etiopathogenesis. Considerable progress has been achieved in understanding the progression of the disease and tear fluid has played a major role in the progress. This review discusses the importance of tear fluid as a source of biomarker for keratoconus and how advances in technology have helped map the complexity of tears and thereby molecular readouts of the disease. Expanding knowledge of the tear proteome, lipidome and metabolome opened up new avenues to study keratoconus and to identify probable prognostic or diagnostic biomarkers for the disease. A multidimensional approach of analyzing tear fluid of patients layering on proteomics, lipidomics and metabolomics is necessary in effectively decoding keratoconus and thereby identifying targets for its treatment.",2016 Aug 4,"['Nishtala, Krishnatej', 'Pahuja, Natasha', 'Shetty, Rohit', 'Nuijts, Rudy M. M. A.', 'Ghosh, Arkasubhra']",Eye Vis (Lond),,,True
46605a285131acb104ba6ed5a7b15a23839bdb49,PMC,Transmission or Within-Host Dynamics Driving Pulses of Zoonotic Viruses in Reservoir–Host Populations,http://dx.doi.org/10.1371/journal.pntd.0004796,PMC4973921,27489944,CC0,"Progress in combatting zoonoses that emerge from wildlife is often constrained by limited knowledge of the biology of pathogens within reservoir hosts. We focus on the host–pathogen dynamics of four emerging viruses associated with bats: Hendra, Nipah, Ebola, and Marburg viruses. Spillover of bat infections to humans and domestic animals often coincides with pulses of viral excretion within bat populations, but the mechanisms driving such pulses are unclear. Three hypotheses dominate current research on these emerging bat infections. First, pulses of viral excretion could reflect seasonal epidemic cycles driven by natural variations in population densities and contact rates among hosts. If lifelong immunity follows recovery, viruses may disappear locally but persist globally through migration; in either case, new outbreaks occur once births replenish the susceptible pool. Second, epidemic cycles could be the result of waning immunity within bats, allowing local circulation of viruses through oscillating herd immunity. Third, pulses could be generated by episodic shedding from persistently infected bats through a combination of physiological and ecological factors. The three scenarios can yield similar patterns in epidemiological surveys, but strategies to predict or manage spillover risk resulting from each scenario will be different. We outline an agenda for research on viruses emerging from bats that would allow for differentiation among the scenarios and inform development of evidence-based interventions to limit threats to human and animal health. These concepts and methods are applicable to a wide range of pathogens that affect humans, domestic animals, and wildlife.",2016 Aug 4,"['Plowright, Raina K.', 'Peel, Alison J.', 'Streicker, Daniel G.', 'Gilbert, Amy T.', 'McCallum, Hamish', 'Wood, James', 'Baker, Michelle L.', 'Restif, Olivier']",PLoS Negl Trop Dis,,,True
d2b714f43fa6302301a1aa7d282de555f71024b2,PMC,Germinal Center B Cell and T Follicular Helper Cell Responses to Viral Vector and Protein-in-Adjuvant Vaccines,http://dx.doi.org/10.4049/jimmunol.1502472,PMC4974488,27412417,CC BY,"There is great interest in the development of Ab-inducing subunit vaccines targeting infections, including HIV, malaria, and Ebola. We previously reported that adenovirus vectored vaccines are potent in priming Ab responses, but uncertainty remains regarding the optimal approach for induction of humoral immune responses. In this study, using OVA as a model Ag, we assessed the magnitude of the primary and anamnestic Ag–specific IgG responses of mice to four clinically relevant vaccine formulations: replication-deficient adenovirus; modified vaccinia Ankara (a poxvirus); protein with alum; and protein in the squalene oil-in-water adjuvant Addavax. We then used flow cytometric assays capable of measuring total and Ag-specific germinal center (GC) B cell and follicular Th cell responses to compare the induction of these responses by the different formulations. We report that adenovirus vectored vaccines induce Ag insert–specific GC B cell and Ab responses of a magnitude comparable to those induced by a potent protein/squalene oil-in-water formulation whereas—despite a robust overall GC response—the insert-specific GC B cell and Ab responses induced by modified vaccinia Ankara were extremely weak. Ag-specific follicular Th cell responses to adenovirus vectored vaccines exceeded those induced by other platforms at day 7 after immunization. We found little evidence that innate immune activation by adenovirus may act as an adjuvant in such a manner that the humoral response to a recombinant protein may be enhanced by coadministering with an adenovirus lacking a transgene of interest. Overall, these studies provide further support for the use of replication-deficient adenoviruses to induce humoral responses.",2016 Aug 15,"['Wang, Chuan', 'Hart, Matthew', 'Chui, Cecilia', 'Ajuogu, Augustine', 'Brian, Iona J.', 'de Cassan, Simone C.', 'Borrow, Persephone', 'Draper, Simon J.', 'Douglas, Alexander D.']",J Immunol,,,True
649b2f2aba88c512775160f197a250e51ac8bc14,PMC,Replication-Competent Influenza A Viruses Expressing Reporter Genes,http://dx.doi.org/10.3390/v8070179,PMC4974514,27347991,CC BY,"Influenza A viruses (IAV) cause annual seasonal human respiratory disease epidemics. In addition, IAV have been implicated in occasional pandemics with inordinate health and economic consequences. Studying IAV, in vitro or in vivo, requires the use of laborious secondary methodologies to identify virus-infected cells. To circumvent this requirement, replication-competent IAV expressing an easily traceable reporter protein can be used. Here we discuss the development and applications of recombinant replication-competent IAV harboring diverse fluorescent or bioluminescent reporter genes in different locations of the viral genome. These viruses have been employed for in vitro and in vivo studies, such as the screening of neutralizing antibodies or antiviral compounds, the identification of host factors involved in viral replication, cell tropism, the development of vaccines, or the assessment of viral infection dynamics. In summary, reporter-expressing, replicating-competent IAV represent a powerful tool for the study of IAV both in vitro and in vivo.",2016 Jun 23,"['Breen, Michael', 'Nogales, Aitor', 'Baker, Steven F.', 'Martínez-Sobrido, Luis']",Viruses,,,True
e3fe1b272c977754c55719ab93e90ecb0b9472d5,PMC,Who Regulates Whom? An Overview of RNA Granules and Viral Infections,http://dx.doi.org/10.3390/v8070180,PMC4974515,27367717,CC BY,"After viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mRNA translation (protein synthesis) and the assembly of RNA granules. Two of these RNA granules have been well characterized in yeast and mammalian cells, stress granules (SGs), which are translationally silent sites of RNA triage and processing bodies (PBs), which are involved in mRNA degradation. This review discusses the role of these RNA granules in the evasion of anti-viral stress responses through virus-induced remodeling of cellular ribonucleoproteins (RNPs).",2016 Jun 28,"['Poblete-Durán, Natalia', 'Prades-Pérez, Yara', 'Vera-Otarola, Jorge', 'Soto-Rifo, Ricardo', 'Valiente-Echeverría, Fernando']",Viruses,,,True
a51a3f793ea6a59523eff2c0fe6555b729840084,PMC,Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines,http://dx.doi.org/10.3390/v8070183,PMC4974518,27384578,CC BY,"Viral vaccine vectors have shown to be effective in inducing a robust immune response against the vaccine antigen. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising vaccine vector against human and veterinary pathogens. Avirulent NDV strains LaSota and B1 have long track records of safety and efficacy. Therefore, use of these strains as vaccine vectors is highly safe in avian and non-avian species. NDV replicates efficiently in the respiratory track of the host and induces strong local and systemic immune responses against the foreign antigen. As a vaccine vector, NDV can accommodate foreign sequences with a good degree of stability and as a RNA virus, there is limited possibility for recombination with host cell DNA. Using NDV as a vaccine vector in humans offers several advantages over other viral vaccine vectors. NDV is safe in humans due to host range restriction and there is no pre-existing antibody to NDV in the human population. NDV is antigenically distinct from common human pathogens. NDV replicates to high titer in a cell line acceptable for human vaccine development. Therefore, NDV is an attractive vaccine vector for human pathogens for which vaccines are currently not available. NDV is also an attractive vaccine vector for animal pathogens.",2016 Jul 4,"['Kim, Shin-Hee', 'Samal, Siba K.']",Viruses,,,True
5fc3eedb09f3b7624fec7d2b9afedfffbab47a21,PMC,Regulation of Stress Responses and Translational Control by Coronavirus,http://dx.doi.org/10.3390/v8070184,PMC4974519,27384577,CC BY,"Similar to other viruses, coronavirus infection triggers cellular stress responses in infected host cells. The close association of coronavirus replication with the endoplasmic reticulum (ER) results in the ER stress responses, which impose a challenge to the viruses. Viruses, in turn, have come up with various mechanisms to block or subvert these responses. One of the ER stress responses is inhibition of the global protein synthesis to reduce the amount of unfolded proteins inside the ER lumen. Viruses have evolved the capacity to overcome the protein translation shutoff to ensure viral protein production. Here, we review the strategies exploited by coronavirus to modulate cellular stress response pathways. The involvement of coronavirus-induced stress responses and translational control in viral pathogenesis will also be briefly discussed.",2016 Jul 4,"['Fung, To Sing', 'Liao, Ying', 'Liu, Ding Xiang']",Viruses,,,True
467143e07e3d6ec8a0617a5bdee446ab2c63581c,PMC,"The Role of Phlebovirus Glycoproteins in Viral Entry, Assembly and Release",http://dx.doi.org/10.3390/v8070202,PMC4974537,27455305,CC BY,"Bunyaviruses are enveloped viruses with a tripartite RNA genome that can pose a serious threat to animal and human health. Members of the Phlebovirus genus of the family Bunyaviridae are transmitted by mosquitos and ticks to humans and include highly pathogenic agents like Rift Valley fever virus (RVFV) and severe fever with thrombocytopenia syndrome virus (SFTSV) as well as viruses that do not cause disease in humans, like Uukuniemi virus (UUKV). Phleboviruses and other bunyaviruses use their envelope proteins, Gn and Gc, for entry into target cells and for assembly of progeny particles in infected cells. Thus, binding of Gn and Gc to cell surface factors promotes viral attachment and uptake into cells and exposure to endosomal low pH induces Gc-driven fusion of the viral and the vesicle membranes. Moreover, Gn and Gc facilitate virion incorporation of the viral genome via their intracellular domains and Gn and Gc interactions allow the formation of a highly ordered glycoprotein lattice on the virion surface. Studies conducted in the last decade provided important insights into the configuration of phlebovirus Gn and Gc proteins in the viral membrane, the cellular factors used by phleboviruses for entry and the mechanisms employed by phlebovirus Gc proteins for membrane fusion. Here, we will review our knowledge on the glycoprotein biogenesis and the role of Gn and Gc proteins in the phlebovirus replication cycle.",2016 Jul 21,"['Spiegel, Martin', 'Plegge, Teresa', 'Pöhlmann, Stefan']",Viruses,,,True
33bfc254b350a34f254ea0c56d349ddae719048b,PMC,Local Innate Responses to TLR Ligands in the Chicken Trachea,http://dx.doi.org/10.3390/v8070207,PMC4974541,27455308,CC BY,"The chicken upper respiratory tract is the portal of entry for respiratory pathogens, such as avian influenza virus (AIV). The presence of microorganisms is sensed by pathogen recognition receptors (such as Toll-like receptors (TLRs)) of the innate immune defenses. Innate responses are essential for subsequent induction of potent adaptive immune responses, but little information is available about innate antiviral responses of the chicken trachea. We hypothesized that TLR ligands induce innate antiviral responses in the chicken trachea. Tracheal organ cultures (TOC) were used to investigate localized innate responses to TLR ligands. Expression of candidate genes, which play a role in antiviral responses, was quantified. To confirm the antiviral responses of stimulated TOC, chicken macrophages were treated with supernatants from stimulated TOC, prior to infection with AIV. The results demonstrated that TLR ligands induced the expression of pro-inflammatory cytokines, type I interferons and interferon stimulated genes in the chicken trachea. In conclusion, TLR ligands induce functional antiviral responses in the chicken trachea, which may act against some pathogens, such as AIV.",2016 Jul 22,"['Barjesteh, Neda', 'Alkie, Tamiru Negash', 'Hodgins, Douglas C.', 'Nagy, Éva', 'Sharif, Shayan']",Viruses,,,True
9a13ccd6be3536af404c25e748c34eac997c5d16,PMC,Expression of Cystic Fibrosis Transmembrane Conductance Regulator in Ganglia of Human Gastrointestinal Tract,http://dx.doi.org/10.1038/srep30926,PMC4974654,27491544,CC BY,"CF is caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) which is an anion selective transmembrane ion channel that mainly regulates chloride transport, expressed in the epithelia of various organs. Recently, we have demonstrated CFTR expression in the brain, the spinal cord and the sympathetic ganglia. This study aims to investigate the expression and distribution of CFTR in the ganglia of the human gastrointestinal tract. Fresh tissue and formalin-fixed paraffin-embedded normal gastrointestinal tract samples were collected from eleven surgical patients and five autopsy cases. Immunohistochemistry, in situ hybridization, laser-assisted microdissection and nested reverse transcriptase polymerase chain reaction were performed. Expression of CFTR protein and mRNA was detected in neurons of the ganglia of all segments of the human gastrointestinal tract examined, including the stomach, duodenum, jejunum, ileum, cecum, appendix, colon and rectum. The extensive expression of CFTR in the enteric ganglia suggests that CFTR may play a role in the physiology of the innervation of the gastro-intestinal tract. The presence of dysfunctional CFTRs in enteric ganglia could, to a certain extent, explain the gastrointestinal symptoms frequently experienced by CF patients.",2016 Aug 5,"['Xue, Ruiqi', 'Gu, Huan', 'Qiu, Yamei', 'Guo, Yong', 'Korteweg, Christine', 'Huang, Jin', 'Gu, Jiang']",Sci Rep,,,True
1329ea9b040bdc8af7c30f7ba4b5755e352deae8,PMC,Occurrence and sequence analysis of porcine deltacoronaviruses in southern China,http://dx.doi.org/10.1186/s12985-016-0591-6,PMC4974758,27496131,CC BY,"BACKGROUND: Following the initial isolation of porcine deltacoronavirus (PDCoV) from pigs with diarrheal disease in the United States in 2014, the virus has been detected on swine farms in some provinces of China. To date, little is known about the molecular epidemiology of PDCoV in southern China where major swine production is operated. RESULTS: To investigate the prevalence of PDCoV in this region and compare its activity to other enteric disease of swine caused by porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis coronavirus (TGEV), and porcine rotavirus group C (Rota C), 390 fecal samples were collected from swine of various ages from 15 swine farms with reported diarrhea. Fecal samples were tested by reverse transcription-PCR (RT-PCR) that targeted PDCoV, PEDV, TGEV, and Rota C, respectively. PDCoV was detected exclusively from nursing piglets with an overall prevalence of approximate 1.28 % (5/390), not in suckling and fattening piglets. Interestingly, all of PDCoV-positive samples were from 2015 rather than 2012–2014. Despite a low detection rate, PDCoV emerged in each province/region of southern China. In addition, compared to TGEV (1.54 %, 5/390) or Rota C (1.28 %, 6/390), there were highly detection rates of PEDV (22.6 %, 88/390) in those samples. Notably, all five PDCoV-positive piglets were co-infected by PEDV. Furthermore, phylogenetic analysis of spike (S) and nucleocapsid (N) gene sequences of PDCoVs revealed that currently circulating PDCoVs in southern China were more closely related to other Chinese strains of PDCoVs than to those reported in United States, South Korea and Thailand. CONCLUSIONS: This study demonstrated that PDCoV was present in southern China despite the low prevalence, and supported an evolutionary theory of geographical clustering of PDCoVs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0591-6) contains supplementary material, which is available to authorized users.",2016 Aug 5,"['Zhai, Shao-Lun', 'Wei, Wen-Kang', 'Li, Xiao-Peng', 'Wen, Xiao-Hui', 'Zhou, Xia', 'Zhang, He', 'Lv, Dian-Hong', 'Li, Feng', 'Wang, Dan']",Virol J,,,True
db0b1c57b81cdb3facc4177cf7f6a208eab730b9,PMC,Osteopontin Fragments with Intact Thrombin-Sensitive Site Circulate in Cervical Cancer Patients,http://dx.doi.org/10.1371/journal.pone.0160412,PMC4975440,27494141,CC0,"We investigated whether circulating osteopontin (OPN) could be used as a biomarker for cervical cancer. We employed a monoclonal antibody (mAb 659) specific for the unique and intact thrombin-sensitive site in OPN using an inhibition ELISA. We found significantly higher levels of OPN in 33 cervical cancer patients in both the plasma (mean +/- SD, 612 +/- 106 ng/mL) and serum (424 +/- 121 ng/mL) compared to healthy subjects [409 +/- 56 ng/mL, from 31 plasma samples (P < 0.0001), and 314 +/- 98 ng/mL, from 32 serum samples (P = 0.0002), respectively]. Similar results were obtained when the plasma from a bigger group (147 individuals) of cervical cancer patients (560 +/- 211 ng/mL) were compared with the same plasma samples of the healthy individuals (P = 0.0014). More significantly, the OPN level was highest in stage III-IV disease (614 +/- 210 ng/mL, from 52 individuals; P = 0.0001) and least and non-discriminatory in stage I (473 +/- 110 ng/mL, from 40 individuals; P = 0.5318). No such discrimination was found when a mAb of a different specificity (mAb 446) was used in a similar inhibition ELISA to compare the two groups in the first study; a commercial capture ELISA also failed. The possibility that the target epitope recognized by the antibody probe in these assays was absent from the circulating OPN due to protein truncation was supported by gel fractionation of the OPN found in patients’ plasma: 60–64 kDa fragments were found instead of the presumably full-length OPN (68 kDa) seen in healthy people. How these fragments are generated and what possible role they play in cancer biology remain interesting questions.",2016 Aug 5,"['Leung, Danny T. M.', 'Lim, Pak-Leong', 'Cheung, Tak-Hong', 'Wong, Raymond R. Y.', 'Yim, So-Fan', 'Ng, Margaret H. L.', 'Tam, Frankie C. H.', 'Chung, Tony K. H.', 'Wong, Yick-Fu']",PLoS One,,,True
a286c95345592981acce2ffe297605fd083d9fe7,PMC,"Molecular Characterization of the ORF3 and S1 Genes of Porcine Epidemic Diarrhea Virus Non S-INDEL Strains in Seven Regions of China, 2015",http://dx.doi.org/10.1371/journal.pone.0160561,PMC4975444,27494026,CC BY,"In an effort to trace the evolution of porcine epidemic diarrhea virus (PEDV), S1 and ORF3 genes of viruses identified in 41 pig farms from seven regions (North, Northeast, Northwest, Central, East, South West, and South, respectively) of China in 2015 were sequenced and analyzed. Sequence analysis revealed that the 41 ORF3 genes and 29 S1 genes identified in our study exhibited nucleotide homologies of 98.2%–100% and 96.6%–100%, respectively; these two genes exhibited low nucleotide sequence similarities with classical CV777 strain and early Chinese strain LZC. Phylogenetic analysis indicated that the identified PEDV strains belonged to global non S-INDEL strains, and exhibited genetic diversity; S1 gene of the HLJ2015/DP1-1 strain harbored an unique deletion of 12 nucleotides (A(1130)CAACTCCACTG(1141)); while the Chinese PEDV S-INDEL reference strains included two types of the “CV777” S-INDEL as well as the “US” S-INDEL, and all co-circulated with Chinese non S-INDEL strains. Of 29 identified S1 genes, the SS2 epitope (Y(748)SNIGVCK(755)) was highly conserved, while the SS6 epitope (L(764)QDGQVKI(771)) and pAPN receptor-binding region (aa 490–615) exhibited amino substitutions. Nine possible recombination events were identified between the 29 identifed S1 genes and the 3 S1 reference genes from early Chinese PEDV strains. The complete S genes of selected Chinese PEDV field strains (2011–2015) showed 5.18%–6.07% nucleotide divergence, which is far higher than the divergence observed in early Chinese PEDV strains (3.1%) (P<0.05). Our data provide evidence that PEDV non S-INDEL strains with genetic diversities and potential recombination circulate in seven regions of China in 2015; Chinese PEDV S-INDEL strains exhibit genetic diversity and co-circulate with non S-INDEL strains.",2016 Aug 5,"['Wang, Enyu', 'Guo, Donghua', 'Li, Chunqiu', 'Wei, Shan', 'Wang, Zhihui', 'Liu, Qiujin', 'Zhang, Bei', 'Kong, Fanzhi', 'Feng, Li', 'Sun, Dongbo']",PLoS One,,,True
283047560dd3e30f1161338e0f4f2fcc335328f1,PMC,Passive immunization does not provide protection against experimental infection with Mycoplasma haemofelis,http://dx.doi.org/10.1186/s13567-016-0361-x,PMC4975915,27496124,CC BY,"Mycoplasma haemofelis (Mhf) is the most pathogenic feline hemotropic mycoplasma. Cats infected with Mhf that clear bacteremia are protected from Mhf reinfection, but the mechanisms of protective immunity are unresolved. In the present study we investigated whether the passive transfer of antibodies from Mhf-recovered cats to naïve recipient cats provided protection against bacteremia and clinical disease following homologous challenge with Mhf; moreover, we characterized the immune response in the recipient cats. Ten specified pathogen-free (SPF) cats were transfused with pooled plasma from cats that had cleared Mhf bacteremia; five control cats received plasma from naïve SPF cats. After homologous challenge with Mhf, cats were monitored for 100 days using quantitative PCR, hematology, blood biochemistry, Coombs testing, flow cytometry, DnaK ELISA, and red blood cell (RBC) osmotic fragility (OF) measurement. Passively immunized cats were not protected against Mhf infection but, compared to control cats, showed significantly higher RBC OF and B lymphocyte (CD45R/B220(+)) counts and occasionally higher lymphocyte, monocyte and activated CD4(+) T lymphocyte (CD4(+)CD25(+)) counts; they also showed higher bilirubin, total protein and globulin levels compared to those of control cats. At times of peak bacteremia, a decrease in eosinophils and lymphocytes, as well as subsets thereof (B lymphocytes and CD5(+), CD4(+) and CD8(+) T lymphocytes), and an increase in monocytes were particularly significant in the passively immunized cats. In conclusion, passive immunization does not prevent bacteremia and clinical disease following homologous challenge with Mhf, but enhances RBC osmotic fragility and induces a pronounced immune response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0361-x) contains supplementary material, which is available to authorized users.",2016 Aug 5,"['Sugiarto, Sarah', 'Spiri, Andrea M.', 'Riond, Barbara', 'Novacco, Marilisa', 'Oestmann, Angelina', 'de Miranda, Luisa H. Monteiro', 'Meli, Marina L.', 'Boretti, Felicitas S.', 'Hofmann-Lehmann, Regina', 'Willi, Barbara']",Vet Res,,,True
729e5d420ec1a80d31928dc8bb261610a93aa890,PMC,Structure and Function of HLA-A*02-Restricted Hantaan Virus Cytotoxic T-Cell Epitope That Mediates Effective Protective Responses in HLA-A2.1/K(b) Transgenic Mice,http://dx.doi.org/10.3389/fimmu.2016.00298,PMC4976285,27551282,CC BY,"Hantavirus infections cause severe emerging diseases in humans and are associated with high mortality rates; therefore, they have become a global public health concern. Our previous study showed that the CD8(+) T-cell epitope aa129–aa137 (FVVPILLKA, FA9) of the Hantaan virus (HTNV) nucleoprotein (NP), restricted by human leukocyte antigen (HLA)-A*02, induced specific CD8(+) T-cell responses that controlled HTNV infection in humans. However, the in vivo immunogenicity of peptide FA9 and the effect of FA9-specific CD8(+) T-cell immunity remain unclear. Here, based on a detailed structural analysis of the peptide FA9/HLA-A*0201 complex and functional investigations using HLA-A2.1/K(b) transgenic (Tg) mice, we found that the overall structure of the peptide FA9/HLA-A*0201 complex displayed a typical MHC class I fold with Val2 and Ala9 as primary anchor residues and Val3 and Leu7 as secondary anchor residues that allow peptide FA9 to bind tightly with an HLA-A*0201 molecule. Residues in the middle portion of peptide FA9 extruding out of the binding groove may be the sites that allow for recognition by T-cell receptors. Immunization with peptide FA9 in HLA-A2.1/K(b) Tg mice induced FA9-specific cytotoxic T-cell responses characterized by the induction of high expression levels of interferon-γ, tumor necrosis factor-α, granzyme B, and CD107a. In an HTNV challenge trial, significant reductions in the levels of both the antigens and the HTNV RNA loads were observed in the liver, spleen, and kidneys of Tg mice pre-vaccinated with peptide FA9. Thus, our findings highlight the ability of HTNV epitope-specific CD8(+) T-cell immunity to control HTNV and support the possibility that the HTNV-NP FA9 peptide, naturally processed in vivo in an HLA-A*02-restriction manner, may be a good candidate for the development HTNV peptide vaccines.",2016 Aug 8,"['Ma, Ying', 'Cheng, Linfeng', 'Yuan, Bin', 'Zhang, Yusi', 'Zhang, Chunmei', 'Zhang, Yun', 'Tang, Kang', 'Zhuang, Ran', 'Chen, Lihua', 'Yang, Kun', 'Zhang, Fanglin', 'Jin, Boquan']",Front Immunol,,,True
2bf72671f78524129acb86ceef6c598e10c7daa7,PMC,Structure of a Highly Active Cephalopod S-crystallin Mutant: New Molecular Evidence for Evolution from an Active Enzyme into Lens-Refractive Protein,http://dx.doi.org/10.1038/srep31176,PMC4976375,27499004,CC BY,"Crystallins are found widely in animal lenses and have important functions due to their refractive properties. In the coleoid cephalopods, a lens with a graded refractive index provides good vision and is required for survival. Cephalopod S-crystallin is thought to have evolved from glutathione S-transferase (GST) with various homologs differentially expressed in the lens. However, there is no direct structural information that helps to delineate the mechanisms by which S-crystallin could have evolved. Here we report the structural and biochemical characterization of novel S-crystallin-glutathione complex. The 2.35-Å crystal structure of a S-crystallin mutant from Octopus vulgaris reveals an active-site architecture that is different from that of GST. S-crystallin has a preference for glutathione binding, although almost lost its GST enzymatic activity. We’ve also identified four historical mutations that are able to produce a “GST-like” S-crystallin that has regained activity. This protein recapitulates the evolution of S-crystallin from GST. Protein stability studies suggest that S-crystallin is stabilized by glutathione binding to prevent its aggregation; this contrasts with GST-σ, which do not possess this protection. We suggest that a tradeoff between enzyme activity and the stability of the lens protein might have been one of the major driving force behind lens evolution.",2016 Aug 8,"['Tan, Wei-Hung', 'Cheng, Shu-Chun', 'Liu, Yu-Tung', 'Wu, Cheng-Guo', 'Lin, Min-Han', 'Chen, Chiao-Che', 'Lin, Chao-Hsiung', 'Chou, Chi-Yuan']",Sci Rep,,,True
e9af8ceed4b7a1f1cfbd6adcc0b9bff83b271f5b,PMC,Structure of a Highly Active Cephalopod S-crystallin Mutant: New Molecular Evidence for Evolution from an Active Enzyme into Lens-Refractive Protein,http://dx.doi.org/10.1038/srep31176,PMC4976375,27499004,CC BY,"Crystallins are found widely in animal lenses and have important functions due to their refractive properties. In the coleoid cephalopods, a lens with a graded refractive index provides good vision and is required for survival. Cephalopod S-crystallin is thought to have evolved from glutathione S-transferase (GST) with various homologs differentially expressed in the lens. However, there is no direct structural information that helps to delineate the mechanisms by which S-crystallin could have evolved. Here we report the structural and biochemical characterization of novel S-crystallin-glutathione complex. The 2.35-Å crystal structure of a S-crystallin mutant from Octopus vulgaris reveals an active-site architecture that is different from that of GST. S-crystallin has a preference for glutathione binding, although almost lost its GST enzymatic activity. We’ve also identified four historical mutations that are able to produce a “GST-like” S-crystallin that has regained activity. This protein recapitulates the evolution of S-crystallin from GST. Protein stability studies suggest that S-crystallin is stabilized by glutathione binding to prevent its aggregation; this contrasts with GST-σ, which do not possess this protection. We suggest that a tradeoff between enzyme activity and the stability of the lens protein might have been one of the major driving force behind lens evolution.",2016 Aug 8,"['Tan, Wei-Hung', 'Cheng, Shu-Chun', 'Liu, Yu-Tung', 'Wu, Cheng-Guo', 'Lin, Min-Han', 'Chen, Chiao-Che', 'Lin, Chao-Hsiung', 'Chou, Chi-Yuan']",Sci Rep,,,False
d9c950cf19a2048596a6e143471fb2d0c009d8f0,PMC,"System effectiveness of detection, brief intervention and refer to treatment for the people with post-traumatic emotional distress by MERS: a case report of community-based proactive intervention in South Korea",http://dx.doi.org/10.1186/s13033-016-0083-5,PMC4976505,27504141,CC BY,"BACKGROUND: Korea has experienced diverse kind of disasters these days. Among them the 2015 middle eastern respiratory syndrome (MERS) outbreak imposed great psychological stress on almost all Korean citizens. Following the MERS outbreak, government is reviewing overall infectious disease management system and prioritizing the establishment of mental health service systems for infectious disease. This study makes suggestions for implementing disaster-related mental health service systems by analyzing the example of Gyeonggi Province, which proactively intervened with residents’ psychological problems caused by the large-scale outbreak of an infectious disease. CASE DESCRIPTION: Mental health service system for MERS victims had the following two parts: a mental health service for people who had been placed in quarantine and a service provided to families of patients who had died or recovered patients. The government of Gyeonggi province, public health centers, regional and local Community Mental Health Centers and the National Center for Crisis Mental Health Management participated in this service system. Among 1221 Gyeonggi people placed in quarantine and who experienced psychological and emotional difficulties, 350 required continuing services; 124 of this group received continuing services. That is, 35 % of people who required psychological intervention received contact from service providers and received the required services. CONCLUSIONS: This study reflects a proactive monitoring system for thousands of people placed under quarantine for the first time in Korea. It is significant that the service utilization rate by a proactive manner, that is the professionals administering it actively approached and contacted people with problems rather than passively providing information was much higher than other general mental health situation in Korea. The core value of public mental health services is adequate public accessibility; it is therefore essential for governments to strengthen their professional competence and establish effective systems. These criteria should also be applied to psychological problems caused by disastrous infectious disease outbreaks.",2016 Aug 8,"['Yoon, Mi-Kyung', 'Kim, Soon-Young', 'Ko, Hye-Sun', 'Lee, Myung-Soo']",Int J Ment Health Syst,,,True
ebf7e1110aa56a3066f9590befe475eb12b3eaa1,PMC,Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity,http://dx.doi.org/10.1371/journal.pone.0160606,PMC4976934,27500954,CC BY,"BACKGROUND: Despite a high burden of respiratory syncytial virus (RSV) infections among children, data on demographic and clinical characteristics of RSV are scarce in low and middle income countries. This study aims to describe the viral etiologies, the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections (LRTI), focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity. METHODS: A prospective study among children under two years of age, hospitalized with LRTI was conducted in two referral pediatric hospitals in Ho Chi Minh City, Vietnam, from May 2009 to December 2010. Socio-demographic, clinical data and nasopharyngeal swabs were collected on enrolment and discharge. Multiplex real-time RT-PCR (13 viruses) and quantitative RSV RT-PCR were used to identify viral pathogens, RSV load and subgroups. RESULTS: Among 632 cases, 48% were RSV positive. RSV infections occurred at younger age than three other leading viral infections i.e rhinovirus (RV), metapneumovirus (MPV), parainfluenza virus (PIV-3) and were significantly more frequent in the first 6 months of life. Clinical severity score of RSV infection was significantly higher than PIV-3 but not for RV or MPV. In multivariate analysis, RV infection was significantly associated with severity while RSV infection was not. Among RSV infections, neither viral load nor viral co-infections were significantly associated with severity. Young age and having fever at admission were significantly associated with both RSV and LRTI severity. A shift in RSV subgroup predominance was observed during two consecutive rainy seasons but was not associated with severity. CONCLUSION: We report etiologies, the epidemiological and clinical characteristics of LRTI among hospitalized children under two years of age and risk factors of RSV and LRTI severity.",2016 Aug 8,"['Do, Lien Anh Ha', 'Bryant, Juliet E.', 'Tran, Anh Tuan', 'Nguyen, Bach Hue', 'Tran, Thi Thu Loan', 'Tran, Quynh Huong', 'Vo, Quoc Bao', 'Tran Dac, Nguyen Anh', 'Trinh, Hong Nhien', 'Nguyen, Thi Thanh Hai', 'Le Binh, Bao Tinh', 'Le, Khanh', 'Nguyen, Minh Tien', 'Thai, Quang Tung', 'Vo, Thanh Vu', 'Ngo, Ngoc Quang Minh', 'Dang, Thi Kim Huyen', 'Cao, Ngoc Huong', 'Tran, Thu Van', 'Ho, Lu Viet', 'Farrar, Jeremy', 'de Jong, Menno', 'van Doorn, H. Rogier']",PLoS One,,,True
a65111e0e1a8f26d4789ea6439cae1cfa5b391b8,PMC,A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome,http://dx.doi.org/10.3389/fnhum.2016.00403,PMC4977292,27555815,CC BY,"Owing to the reports of microcephaly as a consistent outcome in the fetuses of pregnant women infected with ZIKV in Brazil, Zika virus (ZIKV)—microcephaly etiomechanistic relationship has recently been implicated. Researchers, however, are still struggling to establish an embryological basis for this interesting causal handcuff. The present study reveals robust evidence in favor of a plausible ZIKV-microcephaly cause-effect liaison. The rationale is based on: (1) sequence homology between ZIKV genome and the response element of an early neural tube developmental marker “retinoic acid” in human DNA and (2) comprehensive similarities between the details of brain defects in ZIKV-microcephaly and retinoic acid embryopathy. Retinoic acid is considered as the earliest factor for regulating anteroposterior axis of neural tube and positioning of structures in developing brain through retinoic acid response elements (RARE) consensus sequence (5′–AGGTCA–3′) in promoter regions of retinoic acid-dependent genes. We screened genomic sequences of already reported virulent ZIKV strains (including those linked to microcephaly) and other viruses available in National Institute of Health genetic sequence database (GenBank) for the RARE consensus repeats and obtained results strongly bolstering our hypothesis that ZIKV strains associated with microcephaly may act through precipitation of dysregulation in retinoic acid-dependent genes by introducing extra stretches of RARE consensus sequence repeats in the genome of developing brain cells. Additional support to our hypothesis comes from our findings that screening of other viruses for RARE consensus sequence repeats is positive only for those known to display neurotropism and cause fetal brain defects (for which maternal-fetal transmission during developing stage may be required). The numbers of RARE sequence repeats appeared to match with the virulence of screened positive viruses. Although, bioinformatic evidence and embryological features are in favor of our hypothesis, additional studies including animal models are warranted to validate our proposition. Such studies are likely to unfold ZIKV-microcephaly association and may help in devising methods to combat it.",2016 Aug 9,"['Kumar, Ashutosh', 'Singh, Himanshu N.', 'Pareek, Vikas', 'Raza, Khursheed', 'Dantham, Subrahamanyam', 'Kumar, Pavan', 'Mochan, Sankat', 'Faiq, Muneeb A.']",Front Hum Neurosci,,,True
a4ee11dba58a0b0c6566a1fac060b4329bcdc8cd,PMC,Study and interest of cellular load in respiratory samples for the optimization of molecular virological diagnosis in clinical practice,http://dx.doi.org/10.1186/s12879-016-1730-9,PMC4977610,27503120,CC BY,"BACKGROUND: Respiratory viral diagnosis of upper respiratory tract infections has largely developed through multiplex molecular techniques. Although the sensitivity of different types of upper respiratory tract samples seems to be correlated to the number of sampled cells, this link remains largely unexplored. METHODS: Our study included 800 upper respiratory tract specimens of which 400 negative and 400 positive for viral detection in multiplex PCR. All samples were selected and matched for age in these 2 groups. For the positive group, samples were selected for the detected viral species. RESULTS: Among the factors influencing the cellularity were the type of sample (p < 0.0001); patient age (p < 0.001); viral positive or negative nature of the sample (p = 0.002); and, for the positive samples, the number of viral targets detected (0.004 < p < 0.049) and viral species. CONCLUSION: The cellular load of upper respiratory samples is multifactorial and occurs for many in the sensitivity of molecular detection. However it was not possible to determine a minimum cellularity threshold allowing molecular viral detection. The differences according to the type of virus remain to be studied on a larger scale.",2016 Aug 9,"['Bonnin, Paul', 'Miszczak, Fabien', 'Kin, Nathalie', 'Resa, Cecile', 'Dina, Julia', 'Gouarin, Stephanie', 'Viron, Florent', 'Morello, Remy', 'Vabret, Astrid']",BMC Infect Dis,,,True
2c7f8c9a78ec06b29ea61f2dd02730d2c3af1cfb,PMC,An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens,http://dx.doi.org/10.1371/journal.ppat.1005804,PMC4978498,27505057,CC0,"The healthy lung maintains a steady state of immune readiness to rapidly respond to injury from invaders. Integrins are important for setting the parameters of this resting state, particularly the epithelial-restricted αVβ6 integrin, which is upregulated during injury. Once expressed, αVβ6 moderates acute lung injury (ALI) through as yet undefined molecular mechanisms. We show that the upregulation of β6 during influenza infection is involved in disease pathogenesis. β6-deficient mice (β6 KO) have increased survival during influenza infection likely due to the limited viral spread into the alveolar spaces leading to reduced ALI. Although the β6 KO have morphologically normal lungs, they harbor constitutively activated lung CD11b(+) alveolar macrophages (AM) and elevated type I IFN signaling activity, which we traced to the loss of β6-activated transforming growth factor-β (TGF-β). Administration of exogenous TGF-β to β6 KO mice leads to reduced numbers of CD11b(+) AMs, decreased type I IFN signaling activity and loss of the protective phenotype during influenza infection. Protection extended to other respiratory pathogens such as Sendai virus and bacterial pneumonia. Our studies demonstrate that the loss of one epithelial protein, αVβ6 integrin, can alter the lung microenvironment during both homeostasis and respiratory infection leading to reduced lung injury and improved survival.",2016 Aug 9,"['Meliopoulos, Victoria A.', 'Van de Velde, Lee-Ann', 'Van de Velde, Nicholas C.', 'Karlsson, Erik A.', 'Neale, Geoff', 'Vogel, Peter', 'Guy, Cliff', 'Sharma, Shalini', 'Duan, Susu', 'Surman, Sherri L.', 'Jones, Bart G.', 'Johnson, Michael D. L.', 'Bosio, Catharine', 'Jolly, Lisa', 'Jenkins, R. Gisli', 'Hurwitz, Julia L.', 'Rosch, Jason W.', 'Sheppard, Dean', 'Thomas, Paul G.', 'Murray, Peter J.', 'Schultz-Cherry, Stacey']",PLoS Pathog,,,True
6865c538b9045fd64c560c10a4f1855300a221a3,PMC,Bat–man disease transmission: zoonotic pathogens from wildlife reservoirs to human populations,http://dx.doi.org/10.1038/cddiscovery.2016.48,PMC4979447,27551536,CC BY,"Bats are natural reservoir hosts and sources of infection of several microorganisms, many of which cause severe human diseases. Because of contact between bats and other animals, including humans, the possibility exists for additional interspecies transmissions and resulting disease outbreaks. The purpose of this article is to supply an overview on the main pathogens isolated from bats that have the potential to cause disease in humans.",2016 Jun 27,"['Allocati, N', 'Petrucci, A G', 'Di Giovanni, P', 'Masulli, M', 'Di Ilio, C', 'De Laurenzi, V']",Cell Death Discov,,,True
77907b0bbf75ae10794ca69d97b9874159db1857,PMC,Visual analytics of geo-social interaction patterns for epidemic control,http://dx.doi.org/10.1186/s12942-016-0059-3,PMC4980799,27510908,CC BY,"BACKGROUND: Human interaction and population mobility determine the spatio-temporal course of the spread of an airborne disease. This research views such spreads as geo-social interaction problems, because population mobility connects different groups of people over geographical locations via which the viruses transmit. Previous research argued that geo-social interaction patterns identified from population movement data can provide great potential in designing effective pandemic mitigation. However, little work has been done to examine the effectiveness of designing control strategies taking into account geo-social interaction patterns. METHODS: To address this gap, this research proposes a new framework for effective disease control; specifically this framework proposes that disease control strategies should start from identifying geo-social interaction patterns, designing effective control measures accordingly, and evaluating the efficacy of different control measures. This framework is used to structure design of a new visual analytic tool that consists of three components: a reorderable matrix for geo-social mixing patterns, agent-based epidemic models, and combined visualization methods. RESULTS: With real world human interaction data in a French primary school as a proof of concept, this research compares the efficacy of vaccination strategies between the spatial–social interaction patterns and the whole areas. The simulation results show that locally targeted vaccination has the potential to keep infection to a small number and prevent spread to other regions. At some small probability, the local control strategies will fail; in these cases other control strategies will be needed. This research further explores the impact of varying spatial–social scales on the success of local vaccination strategies. The results show that a proper spatial–social scale can help achieve the best control efficacy with a limited number of vaccines. CONCLUSIONS: The case study shows how GS-EpiViz does support the design and testing of advanced control scenarios in airborne disease (e.g., influenza). The geo-social patterns identified through exploring human interaction data can help target critical individuals, locations, and clusters of locations for disease control purposes. The varying spatial–social scales can help geographically and socially prioritize limited resources (e.g., vaccines).",2016 Aug 10,"Luo, Wei",Int J Health Geogr,,,True
02c9b77cb2898b1597278dbf32a0c61be93d1983,PMC,Terpene metabolic engineering via nuclear or chloroplast genomes profoundly and globally impacts off‐target pathways through metabolite signalling,http://dx.doi.org/10.1111/pbi.12548,PMC4980996,27507797,CC BY,"The impact of metabolic engineering on nontarget pathways and outcomes of metabolic engineering from different genomes are poorly understood questions. Therefore, squalene biosynthesis genes FARNESYL DIPHOSPHATE SYNTHASE (FPS) and SQUALENE SYNTHASE (SQS) were engineered via the Nicotiana tabacum chloroplast (C), nuclear (N) or both (CN) genomes to promote squalene biosynthesis. SQS levels were ~4300‐fold higher in C and CN lines than in N, but all accumulated ~150‐fold higher squalene due to substrate or storage limitations. Abnormal leaf and flower phenotypes, including lower pollen production and reduced fertility, were observed regardless of the compartment or level of transgene expression. Substantial changes in metabolomes of all lines were observed: levels of 65–120 unrelated metabolites, including the toxic alkaloid nicotine, changed by as much as 32‐fold. Profound effects of transgenesis on nontarget gene expression included changes in the abundance of 19 076 transcripts by up to 2000‐fold in CN; 7784 transcripts by up to 1400‐fold in N; and 5224 transcripts by as much as 2200‐fold in C. Transporter‐related transcripts were induced, and cell cycle‐associated transcripts were disproportionally repressed in all three lines. Transcriptome changes were validated by qRT‐PCR. The mechanism underlying these large changes likely involves metabolite‐mediated anterograde and/or retrograde signalling irrespective of the level of transgene expression or end product, due to imbalance of metabolic pools, offering new insight into both anticipated and unanticipated consequences of metabolic engineering.",2016 Sep 8,"['Pasoreck, Elise K.', 'Su, Jin', 'Silverman, Ian M.', 'Gosai, Sager J.', 'Gregory, Brian D.', 'Yuan, Joshua S.', 'Daniell, Henry']",Plant Biotechnol J,,,True
327803ba593def74cf64634bc148a46935a3dd10,PMC,"Influenza-like illness outbreaks in nursing homes in Corsica, France, 2014–2015: epidemiological and molecular characterization",http://dx.doi.org/10.1186/s40064-016-2957-z,PMC4981007,27563533,CC BY,"BACKGROUND: To study the molecular epidemiology of the influenza outbreaks in nursing homes (NHs) to determine whether multiple influenza strains were involved. METHODS: From September to December 2014, NHs in Corsica were invited to participate in an ongoing daily epidemiological and microbiological surveillance for influenza-like illness (ILI) among residents and health care workers (HCWs). RESULTS: The study involved 12 NHs. Respiratory illness meeting the ILI case definition was observed among 44 residents from whom 22 specimens were collected. Of the 22 residents with a nasopharyngeal sample, 13 (59 %) were positive for at least one of the 11 pathogens analysed. Among these 13 patients, 11 (92 %) presented a confirmed influenza (A/H3N2) and two had another respiratory virus: one human metapneumovirus and one human coronavirus. Of patients with a confirmed influenza A(H3N2), 10 (91 %) were vaccinated against influenza during the 2014–2015 season. Two influenza outbreaks were reported in two NHs, caused by influenza A(H3N2) strains belonging to cluster 3C.3 and 3C.2a. Although antivirals were available, prophylaxis was not used. CONCLUSIONS: Phylogenetic analysis seems to suggest no multiple introduction into the two NHs reporting the two influenza A(H3N2) outbreaks. A number of factors could have contributed to transmitting influenza in NHs including, the absence of administration of antiviral treatment for prophylaxis of all residents/staff regardless of immunization status because of the poor vaccine match during each outbreak, the intensive contacts with incompletely protected residents and HCWs, and the low adherence of NHs to notification of ILI outbreaks to the health authorities. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-016-2957-z) contains supplementary material, which is available to authorized users.",2016 Aug 11,"['Masse, S.', 'Minodier, L.', 'Heuze, G.', 'Blanchon, T.', 'Capai, L.', 'Falchi, A.']",Springerplus,,,True
db3824a1c673ce4d1bb41c065065598089c89578,PMC,Common Genetic Polymorphisms within NFκB-Related Genes and the Risk of Developing Invasive Aspergillosis,http://dx.doi.org/10.3389/fmicb.2016.01243,PMC4982195,27570521,CC BY,"Invasive Aspergillosis (IA) is an opportunistic infection caused by Aspergillus, a ubiquitously present airborne pathogenic mold. A growing number of studies suggest a major host genetic component in disease susceptibility. Here, we evaluated whether 14 single-nucleotide polymorphisms within NFκB1, NFκB2, RelA, RelB, Rel, and IRF4 genes influence the risk of IA in a population of 834 high-risk patients (157 IA and 677 non-IA) recruited through a collaborative effort involving the aspBIOmics consortium and four European clinical institutions. No significant overall associations between selected SNPs and the risk of IA were found in this large cohort. Although a hematopoietic stem cell transplantation (HSCT)-stratified analysis revealed that carriers of the IRF4(rs12203592T/T) genotype had a six-fold increased risk of developing the infection when compared with those carrying the C allele (OR(REC) = 6.24, 95%CI 1.25–31.2, P = 0.026), the association of this variant with IA risk did not reach significance at experiment-wide significant threshold. In addition, we found an association of the IRF4(AATC) and IRF4(GGTC) haplotypes (not including the IRF4(rs12203592T) risk allele) with a decreased risk of IA but the magnitude of the association was similar to the one observed in the single-SNP analysis, which indicated that the haplotypic effect on IA risk was likely due to the IRF4(rs12203592) SNP. Finally, no evidence of significant interactions among the genetic markers tested and the risk of IA was found. These results suggest that the SNPs on the studied genes do not have a clinically relevant impact on the risk of developing IA.",2016 Aug 12,"['Lupiañez, Carmen B.', 'Villaescusa, María T.', 'Carvalho, Agostinho', 'Springer, Jan', 'Lackner, Michaela', 'Sánchez-Maldonado, José M.', 'Canet, Luz M.', 'Cunha, Cristina', 'Segura-Catena, Juana', 'Alcazar-Fuoli, Laura', 'Solano, Carlos', 'Fianchi, Luana', 'Pagano, Livio', 'Potenza, Leonardo', 'Aguado, José M.', 'Luppi, Mario', 'Cuenca-Estrella, Manuel', 'Lass-Flörl, Cornelia', 'Einsele, Hermann', 'Vázquez, Lourdes', None, 'Ríos-Tamayo, Rafael', 'Loeffler, Jurgen', 'Jurado, Manuel', 'Sainz, Juan']",Front Microbiol,,,True
1ccc635c4d6c62091bbf7df3f8e4f36803ea1a32,PMC,First identification of mammalian orthoreovirus type 3 in diarrheic pigs in Europe,http://dx.doi.org/10.1186/s12985-016-0593-4,PMC4983005,27519739,CC BY,Mammalian Orthoreoviruses 3 (MRV3) have been described in diarrheic pigs from USA and Asia. We firstly detected MRV3 in Europe (Italy) in piglets showing severe diarrhea associated with Porcine Epidemic Diarrhea. The virus was phylogenetically related to European reoviruses of human and bat origin and to US and Chinese pig MRV3.,2016 Aug 12,"['Lelli, Davide', 'Beato, Maria Serena', 'Cavicchio, Lara', 'Lavazza, Antonio', 'Chiapponi, Chiara', 'Leopardi, Stefania', 'Baioni, Laura', 'De Benedictis, Paola', 'Moreno, Ana']",Virol J,,,True
1d32215c90a79509e66eb1f6e3e05b077d08ee1b,PMC,Assembly of Replication-Incompetent African Horse Sickness Virus Particles: Rational Design of Vaccines for All Serotypes,http://dx.doi.org/10.1128/JVI.00548-16,PMC4984648,27279609,CC BY,"African horse sickness virus (AHSV), an orbivirus in the Reoviridae family with nine different serotypes, causes devastating disease in equids. The virion particle is composed of seven proteins organized in three concentric layers, an outer layer made of VP2 and VP5, a middle layer made of VP7, and inner layer made of VP3 that encloses a replicase complex of VP1, VP4, and VP6 and a genome of 10 double-stranded RNA segments. In this study, we sought to develop highly efficacious candidate vaccines against all AHSV serotypes, taking into account not only immunogenic and safety properties but also virus productivity and stability parameters, which are essential criteria for vaccine candidates. To achieve this goal, we first established a highly efficient reverse genetics (RG) system for AHSV serotype 1 (AHSV1) and, subsequently, a VP6-defective AHSV1 strain in combination with in trans complementation of VP6. This was then used to generate defective particles of all nine serotypes, which required the exchange of two to five RNA segments to achieve equivalent titers of particles. All reassortant-defective viruses could be amplified and propagated to high titers in cells complemented with VP6 but were totally incompetent in any other cells. Furthermore, these replication-incompetent AHSV particles were demonstrated to be highly protective against homologous virulent virus challenges in type I interferon receptor (IFNAR)-knockout mice. Thus, these defective viruses have the potential to be used for the development of safe and stable vaccine candidates. The RG system also provides a powerful tool for the study of the role of individual AHSV proteins in virus assembly, morphogenesis, and pathogenesis. IMPORTANCE African horse sickness virus is transmitted by biting midges and causes African horse sickness in equids, with mortality reaching up to 95% in naive horses. Therefore, the development of efficient vaccines is extremely important due to major economic losses in the equine industry. Through the establishment of a highly efficient RG system, replication-deficient viruses of all nine AHSV serotypes were generated. These defective viruses achieved high titers in a cell line complemented with VP6 but failed to propagate in wild-type mammalian or insect cells. Importantly, these candidate vaccine strains showed strong protective efficacy against AHSV infection in an IFNAR(−/−) mouse model.",2016 Jul 27,"['Lulla, Valeria', 'Lulla, Aleksei', 'Wernike, Kerstin', 'Aebischer, Andrea', 'Beer, Martin', 'Roy, Polly']",J Virol,,,True
d26fb6227fcc98e9e8f9fecbedfd47bc4c00e7ba,PMC,Self-Amplifying mRNA Vaccines Expressing Multiple Conserved Influenza Antigens Confer Protection against Homologous and Heterosubtypic Viral Challenge,http://dx.doi.org/10.1371/journal.pone.0161193,PMC4985159,27525409,CC BY,"Current hemagglutinin (HA)-based seasonal influenza vaccines induce vaccine strain-specific neutralizing antibodies that usually fail to provide protection against mismatched circulating viruses. Inclusion in the vaccine of highly conserved internal proteins such as the nucleoprotein (NP) and the matrix protein 1 (M1) was shown previously to increase vaccine efficacy by eliciting cross-reactive T-cells. However, appropriate delivery systems are required for efficient priming of T-cell responses. In this study, we demonstrated that administration of novel self-amplifying mRNA (SAM(®)) vectors expressing influenza NP (SAM(NP)), M1 (SAM(M1)), and NP and M1 (SAM(M1-NP)) delivered with lipid nanoparticles (LNP) induced robust polyfunctional CD4 T helper 1 cells, while NP-containing SAM also induced cytotoxic CD8 T cells. Robust expansions of central memory (T(CM)) and effector memory (T(EM)) CD4 and CD8 T cells were also measured. An enhanced recruitment of NP-specific cytotoxic CD8 T cells was observed in the lungs of SAM(NP)-immunized mice after influenza infection that paralleled with reduced lung viral titers and pathology, and increased survival after homologous and heterosubtypic influenza challenge. Finally, we demonstrated for the first time that the co-administration of RNA (SAM(M1-NP)) and protein (monovalent inactivated influenza vaccine (MIIV)) was feasible, induced simultaneously NP-, M1- and HA-specific T cells and HA-specific neutralizing antibodies, and enhanced MIIV efficacy against a heterologous challenge. In conclusion, systemic administration of SAM vectors expressing conserved internal influenza antigens induced protective immune responses in mice, supporting the SAM(®) platform as another promising strategy for the development of broad-spectrum universal influenza vaccines.",2016 Aug 15,"['Magini, Diletta', 'Giovani, Cinzia', 'Mangiavacchi, Simona', 'Maccari, Silvia', 'Cecchi, Raffaella', 'Ulmer, Jeffrey B.', 'De Gregorio, Ennio', 'Geall, Andrew J.', 'Brazzoli, Michela', 'Bertholet, Sylvie']",PLoS One,,,True
1faad9ed0f7640ab69cac98df7db103f99e66066,PMC,Adaptation in protein fitness landscapes is facilitated by indirect paths,http://dx.doi.org/10.7554/eLife.16965,PMC4985287,27391790,CC BY,"The structure of fitness landscapes is critical for understanding adaptive protein evolution. Previous empirical studies on fitness landscapes were confined to either the neighborhood around the wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph involving only two amino acids at each site. In reality, the dimensionality of protein sequence space is higher (20(L)) and there may be higher-order interactions among more than two sites. Here we experimentally characterized the fitness landscape of four sites in protein GB1, containing 20(4) = 160,000 variants. We found that while reciprocal sign epistasis blocked many direct paths of adaptation, such evolutionary traps could be circumvented by indirect paths through genotype space involving gain and subsequent loss of mutations. These indirect paths alleviate the constraint on adaptive protein evolution, suggesting that the heretofore neglected dimensions of sequence space may change our views on how proteins evolve. DOI: http://dx.doi.org/10.7554/eLife.16965.001",,"['Wu, Nicholas C', 'Dai, Lei', 'Olson, C Anders', 'Lloyd-Smith, James O', 'Sun, Ren']",eLife.; 5:e16965,,,True
9b5d40c82f807736a65c47b53824f36e220ef9d0,PMC,"Incidence and Outcomes of Acute Respiratory Distress Syndrome: A Nationwide Registry-Based Study in Taiwan, 1997 to 2011",http://dx.doi.org/10.1097/MD.0000000000001849,PMC4985407,26512593,CC BY,"Most epidemiological studies of acute respiratory distress syndrome (ARDS) have been conducted in western countries, and studies in Asia are limited. The aim of our study was to evaluate the incidence, in-hospital mortality, and 1-year mortality of ARDS in Taiwan. We conducted a nationwide inpatient cohort study based on the Taiwan National Health Insurance Research Database between 1997 and 2011. A total of 40,876 ARDS patients (68% male; mean age 66 years) were identified by International Classification of Diseases, 9th edition coding and further analyzed for clinical characteristics, medical costs, and mortality. The overall crude incidence of ARDS was 15.74 per 100,000 person-years, and increased from 2.53 to 19.26 per 100,000 person-years during the study period. The age-adjusted incidence of ARDS was 15.19 per 100,000 person-years. The overall in-hospital mortality was 57.8%. In-hospital mortality decreased from 59.7% in 1997 to 47.5% in 2011 (P < 0.001). The in-hospital mortality rate was lowest (33.5%) in the youngest patients (age 18–29 years) and highest (68.2%) in the oldest patients (>80 years, P < 0.001). The overall 1-year mortality rate was 72.1%, and decreased from 75.8% to 54.7% during the study period. Patients who died during hospitalization were older (69 ± 17 versus 62 ± 19, P < 0.001) and predominantly male (69.8% versus 65.3%, P < 0.001). In addition, patients who died during hospitalization had significantly higher medical costs (6421 versus 5825 US Dollars, P < 0.001) and shorter lengths of stay (13 versus 19 days, P < 0.001) than patients who survived. We provide the first large-scale epidemiological analysis of ARDS incidence and outcomes in Asia. Although the overall incidence was lower than has been reported in a prospective US study, this may reflect underdiagnosis by International Classification of Diseases, 9th edition code and identification of only patients with more severe ARDS in this analysis. Overall, there has been a decreasing trend in in-hospital and 1-year mortality rates in recent years, likely because of the implementation of lung-protective ventilation.",2015 Oct 30,"['Chen, Wei', 'Chen, Yih-Yuan', 'Tsai, Ching-Fang', 'Chen, Solomon Chih-Cheng', 'Lin, Ming-Shian', 'Ware, Lorraine B.', 'Chen, Chuan-Mu']",Medicine (Baltimore),,,True
8133996ea269ebe90ba8c1715cf462607997d975,PMC,Insights into the transmission of respiratory infectious diseases through empirical human contact networks,http://dx.doi.org/10.1038/srep31484,PMC4985757,27526868,CC BY,"In this study, we present representative human contact networks among Chinese college students. Unlike schools in the US, human contacts within Chinese colleges are extremely clustered, partly due to the highly organized lifestyle of Chinese college students. Simulations of influenza spreading across real contact networks are in good accordance with real influenza records; however, epidemic simulations across idealized scale-free or small-world networks show considerable overestimation of disease prevalence, thus challenging the widely-applied idealized human contact models in epidemiology. Furthermore, the special contact pattern within Chinese colleges results in disease spreading patterns distinct from those of the US schools. Remarkably, class cancelation, though simple, shows a mitigating power equal to quarantine/vaccination applied on ~25% of college students, which quantitatively explains its success in Chinese colleges during the SARS period. Our findings greatly facilitate reliable prediction of epidemic prevalence, and thus should help establishing effective strategies for respiratory infectious diseases control.",2016 Aug 16,"['Huang, Chunlin', 'Liu, Xingwu', 'Sun, Shiwei', 'Li, Shuai Cheng', 'Deng, Minghua', 'He, Guangxue', 'Zhang, Haicang', 'Wang, Chao', 'Zhou, Yang', 'Zhao, Yanlin', 'Bu, Dongbo']",Sci Rep,,,True
25c68946a75609c08c00a639ba839a67316cd034,PMC,Insights into the transmission of respiratory infectious diseases through empirical human contact networks,http://dx.doi.org/10.1038/srep31484,PMC4985757,27526868,CC BY,"In this study, we present representative human contact networks among Chinese college students. Unlike schools in the US, human contacts within Chinese colleges are extremely clustered, partly due to the highly organized lifestyle of Chinese college students. Simulations of influenza spreading across real contact networks are in good accordance with real influenza records; however, epidemic simulations across idealized scale-free or small-world networks show considerable overestimation of disease prevalence, thus challenging the widely-applied idealized human contact models in epidemiology. Furthermore, the special contact pattern within Chinese colleges results in disease spreading patterns distinct from those of the US schools. Remarkably, class cancelation, though simple, shows a mitigating power equal to quarantine/vaccination applied on ~25% of college students, which quantitatively explains its success in Chinese colleges during the SARS period. Our findings greatly facilitate reliable prediction of epidemic prevalence, and thus should help establishing effective strategies for respiratory infectious diseases control.",2016 Aug 16,"['Huang, Chunlin', 'Liu, Xingwu', 'Sun, Shiwei', 'Li, Shuai Cheng', 'Deng, Minghua', 'He, Guangxue', 'Zhang, Haicang', 'Wang, Chao', 'Zhou, Yang', 'Zhao, Yanlin', 'Bu, Dongbo']",Sci Rep,,,True
ab85c4fceac01205bc463599fa6263a6498528c1,PMC,Pertussis in infants: an underestimated disease,http://dx.doi.org/10.1186/s12879-016-1710-0,PMC4986228,27528377,CC BY,"BACKGROUND: The clinical diagnosis of pertussis is not easy in early infancy since clinical manifestations can overlap with several different diseases. Many cases are often misclassified and underdiagnosed. We conducted a retrospective study on infants to assess how often physicians suspected pertussis and the actual frequency of Bordetella pertussis infections. METHODS: We analyzed all infants with age ≤90 days hospitalized from March 2011 until September 2013 for acute respiratory symptoms tested with a Real Time Polymerase Chain Reaction able to detect Bordetella pertussis and with a Real Time Polymerase Chain Reaction for a multipanel respiratory virus. Therefore, we compared patients with pertussis positive aspirate, patients with respiratory virus positive aspirate and patients with negative aspirate to identify symptoms or clinical findings predictive of pertussis. RESULTS: Out of 215 patients analyzed, 53 were positive for pertussis (24.7 %), 119 were positive for respiratory virus (55.3 %) and 43 had a negative aspirate (20 %). Pertussis was suspected in 22 patients at admission and 16 of them were confirmed by laboratory tests, while 37 infants with different admission diagnosis resulted positive for pertussis. The sensitivity of clinical diagnosis was 30.2 % and the specificity 96.3 %. Infants with pertussis had more often paroxysmal cough, absence of fever and a higher absolute lymphocyte count than infants without pertussis. CONCLUSIONS: Pertussis is a serious disease in infants and it is often unrecognized; some features should help pediatricians to suspect pertussis, but clinical suspicion has a low sensitivity. We suggest a systematic use of Real Time Polymerase Chain Reaction to support the clinical suspicion of pertussis in patients with less than 3 months of age hospitalized with acute respiratory symptoms.",2016 Aug 15,"['Vittucci, Anna Chiara', 'Spuri Vennarucci, Valentina', 'Grandin, Annalisa', 'Russo, Cristina', 'Lancella, Laura', 'Tozzi, Albero Eugenio', 'Bartuli, Andrea', 'Villani, Alberto']",BMC Infect Dis,,,True
2fac2663c1643fe03479ddfc4122ec63bf269803,PMC,Linear Quantitative Profiling Method Fast Monitors Alkaloids of Sophora Flavescens That Was Verified by Tri-Marker Analyses,http://dx.doi.org/10.1371/journal.pone.0161146,PMC4987015,27529425,CC BY,"The present study demonstrated the use of the Linear Quantitative Profiling Method (LQPM) to evaluate the quality of Alkaloids of Sophora flavescens (ASF) based on chromatographic fingerprints in an accurate, economical and fast way. Both linear qualitative and quantitative similarities were calculated in order to monitor the consistency of the samples. The results indicate that the linear qualitative similarity (LQLS) is not sufficiently discriminating due to the predominant presence of three alkaloid compounds (matrine, sophoridine and oxymatrine) in the test samples; however, the linear quantitative similarity (LQTS) was shown to be able to obviously identify the samples based on the difference in the quantitative content of all the chemical components. In addition, the fingerprint analysis was also supported by the quantitative analysis of three marker compounds. The LQTS was found to be highly correlated to the contents of the marker compounds, indicating that quantitative analysis of the marker compounds may be substituted with the LQPM based on the chromatographic fingerprints for the purpose of quantifying all chemicals of a complex sample system. Furthermore, once reference fingerprint (RFP) developed from a standard preparation in an immediate detection way and the composition similarities calculated out, LQPM could employ the classical mathematical model to effectively quantify the multiple components of ASF samples without any chemical standard.",2016 Aug 16,"['Hou, Zhifei', 'Sun, Guoxiang', 'Guo, Yong']",PLoS One,,,True
f217296b50c75def2bfed98fec3db692e9339f70,PMC,Make Data Sharing Routine to Prepare for Public Health Emergencies,http://dx.doi.org/10.1371/journal.pmed.1002109,PMC4987038,27529422,CC0,Jean-Paul Chretien and colleagues argue that recent Ebola and Zika virus outbreaks highlight the importance of data sharing in scientific research.,2016 Aug 16,"['Chretien, Jean-Paul', 'Rivers, Caitlin M.', 'Johansson, Michael A.']",PLoS Med,,,True
858f420ea81730f250e270096dc9efef9831c1dd,PMC,Nearly full-length genome sequence of a novel astrovirus isolated from chickens with ‘white chicks’ condition,http://dx.doi.org/10.1007/s00705-016-2940-6,PMC4987400,27339687,CC BY,"Avian astroviruses (aAstVs) are divided into three species, Avastrovirus 1, Avastrovirus 2, and Avastrovirus 3, but there are a few strains are waiting to be assigned to an official taxonomic group. This study presents the molecular characterization of chicken astrovirus (CAstV), PL/G059/2014, which is involved in the induction of “white chicks” condition. The 7382-nucleotide-long genome sequence was determined by next-generation sequencing using an Illumina MiSeq System. Phylogenetic analysis showed that it has the characteristics that are typical of avian astroviruses. However, overall degree of nucleotide sequence identity was 43.6 % to 73.7 % between PL/G059/2014 and other available genome sequences of aAstV strains. The amino acid sequences of the proteins encoded by ORF1a and ORF1b of the studied strain were very similar (86.5-93.8 % identity) to those of CAstVs 4175 and GA2011, but they were only 32.7-35.2 % identical in the case of ORF2, which is used officially for astrovirus species demarcation. These features could suggest that the PL/G059/2014 strain should be assigned to a new species in the genus Avastrovirus. Moreover, the different phylogenetic topology of PL/G059/2014 and its nucleotide sequence similarity in different genomic regions could suggest that a recombination event occurred during its evolution and that it has ancestors in common with duck astroviruses.",2016 Jun 23,"['Sajewicz-Krukowska, Joanna', 'Domanska-Blicharz, Katarzyna']",Arch Virol,,,True
1aeb1b6c5213c80ebd33f69021776928ee1fc315,PMC,"Brief review of the chicken Major Histocompatibility Complex: the genes, their distribution on chromosome 16, and their contributions to disease resistance",http://dx.doi.org/10.3382/ps/pev379,PMC4988538,26740135,CC BY,"Nearly all genes presently mapped to chicken chromosome 16 (GGA 16) have either a demonstrated role in immune responses or are considered to serve in immunity by reason of sequence homology with immune system genes defined in other species. The genes are best described in regional units. Among these, the best known is the polymorphic major histocompatibility complex-B (MHC-B) region containing genes for classical peptide antigen presentation. Nearby MHC-B is a small region containing two CD1 genes, which encode molecules known to bind lipid antigens and which will likely be found in chickens to present lipids to specialized T cells, as occurs with CD1 molecules in other species. Another region is the MHC-Y region, separated from MHC-B by an intervening region of tandem repeats. Like MHC-B, MHC-Y is polymorphic. It contains specialized class I and class II genes and c-type lectin-like genes. Yet another region, separated from MHC-Y by the single nucleolar organizing region (NOR) in the chicken genome, contains olfactory receptor genes and scavenger receptor genes, which are also thought to contribute to immunity. The structure, distribution, linkages and patterns of polymorphism in these regions, suggest GGA 16 evolves as a microchromosome devoted to immune defense. Many GGA 16 genes are polymorphic and polygenic. At the moment most disease associations are at the haplotype level. Roles of individual MHC genes in disease resistance are documented in only a very few instances. Provided suitable experimental stocks persist, the availability of increasingly detailed maps of GGA 16 genes combined with new means for detecting genetic variability will lead to investigations defining the contributions of individual loci and more applications for immunogenetics in breeding healthy poultry.",2016 Feb 17,"['Miller, Marcia M.', 'Taylor, Robert L.']",Poult Sci,,,True
9db78243c51590cfaaef835ded1163dc55d67cc0,PMC,Sustained Viremia and High Viral Load in Respiratory Tract Secretions Are Predictors for Death in Immunocompetent Adults with Adenovirus Pneumonia,http://dx.doi.org/10.1371/journal.pone.0160777,PMC4988761,27532864,CC BY,"The predictors for fatal adenovirus (AdV) pneumonia among immunocompetent adults are unclear. Laboratory-confirmed, hospitalized AdV pneumonia adults were prospectively enrolled in Beijing Chao-Yang hospital from March to June 2013. Clinical data and serial whole blood and respiratory tract secretions from such patients were collected. Quantitative real-time polymerase chain reaction was performed to quantify the viral load. A total of 14 AdV pneumonia cases were consecutively enrolled, and four of them were fatal. Ten cases were caused by AdV-55, three by AdV-7 and one by AdV-3. There were no differences in age, gender or underlying diseases between the patients in the fatal cases and surviving cases. At admission (on day 5–7 after illness onset), the patients in fatal cases presented higher initial viral loads in respiratory tract secretions (8.578 ± 2.115 vs 6.263 ± 1.225 Log(10) copies/ml, p = 0.023). All patients in fatal cases presented with viremia on day 12–14 (100% vs 66.7%, p = 0.017). A higher initial viral load in the respiratory tract and sustained viremia (more than 2 weeks) may be predictors for fatal clinical outcomes.",2016 Aug 17,"['Gu, Li', 'Qu, Jiuxin', 'Sun, Bing', 'Yu, Xiaomin', 'Li, Hui', 'Cao, Bin']",PLoS One,,,True
81d66de97e0d60ca4e91efa3aa95f684b914a865,PMC,Mass Gatherings and Respiratory Disease Outbreaks in the United States – Should We Be Worried? Results from a Systematic Literature Review and Analysis of the National Outbreak Reporting System,http://dx.doi.org/10.1371/journal.pone.0160378,PMC4990208,27536770,CC0,"BACKGROUND: Because mass gatherings create environments conducive for infectious disease transmission, public health officials may recommend postponing or canceling large gatherings during a moderate or severe pandemic. Despite these recommendations, limited empirical information exists on the frequency and characteristics of mass gathering-related respiratory disease outbreaks occurring in the United States. METHODS: We conducted a systematic literature review to identify articles about mass gathering-related respiratory disease outbreaks occurring in the United States from 2005 to 2014. A standard form was used to abstract information from relevant articles identified from six medical, behavioral and social science literature databases. We also analyzed data from the National Outbreaks Reporting System (NORS), maintained by the Centers for Disease Control and Prevention since 2009, to estimate the frequency of mass gathering-related respiratory disease outbreaks reported to the system. RESULTS: We identified 21 published articles describing 72 mass gathering-related respiratory disease outbreaks. Of these 72, 40 (56%) were associated with agriculture fairs and Influenza A H3N2v following probable swine exposure, and 25 (35%) with youth summer camps and pandemic Influenza A H1N1. Outbreaks of measles (n = 1) and mumps (n = 2) were linked to the international importation of disease. Between 2009 and 2013, 1,114 outbreaks were reported to NORS, including 96 respiratory disease outbreaks due to Legionella. None of these legionellosis outbreaks was linked to a mass gathering according to available data. CONCLUSION: Mass gathering-related respiratory disease outbreaks may be uncommon in the United States, but have been reported from fairs (zoonotic transmission) as well as at camps where participants have close social contact in communal housing. International importation can also be a contributing factor. NORS collects information on certain respiratory diseases and could serve as a platform to monitor mass gathering-related respiratory outbreaks in the future.",2016 Aug 18,"['Rainey, Jeanette J.', 'Phelps, Tiffani', 'Shi, Jianrong']",PLoS One,,,True
83f3e687e4f87182b3c1d4749e27a559c8b5ab26,PMC,Mass Gatherings and Respiratory Disease Outbreaks in the United States – Should We Be Worried? Results from a Systematic Literature Review and Analysis of the National Outbreak Reporting System,http://dx.doi.org/10.1371/journal.pone.0160378,PMC4990208,27536770,CC0,"BACKGROUND: Because mass gatherings create environments conducive for infectious disease transmission, public health officials may recommend postponing or canceling large gatherings during a moderate or severe pandemic. Despite these recommendations, limited empirical information exists on the frequency and characteristics of mass gathering-related respiratory disease outbreaks occurring in the United States. METHODS: We conducted a systematic literature review to identify articles about mass gathering-related respiratory disease outbreaks occurring in the United States from 2005 to 2014. A standard form was used to abstract information from relevant articles identified from six medical, behavioral and social science literature databases. We also analyzed data from the National Outbreaks Reporting System (NORS), maintained by the Centers for Disease Control and Prevention since 2009, to estimate the frequency of mass gathering-related respiratory disease outbreaks reported to the system. RESULTS: We identified 21 published articles describing 72 mass gathering-related respiratory disease outbreaks. Of these 72, 40 (56%) were associated with agriculture fairs and Influenza A H3N2v following probable swine exposure, and 25 (35%) with youth summer camps and pandemic Influenza A H1N1. Outbreaks of measles (n = 1) and mumps (n = 2) were linked to the international importation of disease. Between 2009 and 2013, 1,114 outbreaks were reported to NORS, including 96 respiratory disease outbreaks due to Legionella. None of these legionellosis outbreaks was linked to a mass gathering according to available data. CONCLUSION: Mass gathering-related respiratory disease outbreaks may be uncommon in the United States, but have been reported from fairs (zoonotic transmission) as well as at camps where participants have close social contact in communal housing. International importation can also be a contributing factor. NORS collects information on certain respiratory diseases and could serve as a platform to monitor mass gathering-related respiratory outbreaks in the future.",2016 Aug 18,"['Rainey, Jeanette J.', 'Phelps, Tiffani', 'Shi, Jianrong']",PLoS One,,,False
b8797e77d9c91dd2cab19ba2e67cf32b6dd97bf6,PMC,Mass Gatherings and Respiratory Disease Outbreaks in the United States – Should We Be Worried? Results from a Systematic Literature Review and Analysis of the National Outbreak Reporting System,http://dx.doi.org/10.1371/journal.pone.0160378,PMC4990208,27536770,CC0,"BACKGROUND: Because mass gatherings create environments conducive for infectious disease transmission, public health officials may recommend postponing or canceling large gatherings during a moderate or severe pandemic. Despite these recommendations, limited empirical information exists on the frequency and characteristics of mass gathering-related respiratory disease outbreaks occurring in the United States. METHODS: We conducted a systematic literature review to identify articles about mass gathering-related respiratory disease outbreaks occurring in the United States from 2005 to 2014. A standard form was used to abstract information from relevant articles identified from six medical, behavioral and social science literature databases. We also analyzed data from the National Outbreaks Reporting System (NORS), maintained by the Centers for Disease Control and Prevention since 2009, to estimate the frequency of mass gathering-related respiratory disease outbreaks reported to the system. RESULTS: We identified 21 published articles describing 72 mass gathering-related respiratory disease outbreaks. Of these 72, 40 (56%) were associated with agriculture fairs and Influenza A H3N2v following probable swine exposure, and 25 (35%) with youth summer camps and pandemic Influenza A H1N1. Outbreaks of measles (n = 1) and mumps (n = 2) were linked to the international importation of disease. Between 2009 and 2013, 1,114 outbreaks were reported to NORS, including 96 respiratory disease outbreaks due to Legionella. None of these legionellosis outbreaks was linked to a mass gathering according to available data. CONCLUSION: Mass gathering-related respiratory disease outbreaks may be uncommon in the United States, but have been reported from fairs (zoonotic transmission) as well as at camps where participants have close social contact in communal housing. International importation can also be a contributing factor. NORS collects information on certain respiratory diseases and could serve as a platform to monitor mass gathering-related respiratory outbreaks in the future.",2016 Aug 18,"['Rainey, Jeanette J.', 'Phelps, Tiffani', 'Shi, Jianrong']",PLoS One,,,True
371c9fd77329f6bd62e32c702dfbed1bb5ae2401,PMC,Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1038/srep31629,PMC4990914,27538452,CC BY,"Middle East Respiratory Syndrome coronavirus (MERS-CoV) has repeatedly caused outbreaks in the Arabian Peninsula. To date, no approved medical countermeasures (MCM) are available to combat MERS-CoV infections. Several neutralizing human monoclonal antibodies (mAbs), including m336, a germline-like human mAb, have been chosen as promising MCM for MERS-CoV. However, their clinical development has been hindered by the lack of a robust animal model that recapitulate the morbidity and mortality of human infections. We assessed the prophylactic and therapeutic efficacy of m336 by using well-characterized transgenic mice shown to be highly sensitive to MERS-CoV infection and disease. We found that mice treated with m336 prior to or post lethal MERS-CoV challenging were fully protected, compared to control mice which sufferered from profound weight loss and uniform death within days after infection. Taken together, these results support further development of m336 and other human monoclonal antibodies as potential therapeutics for MERS-CoV infection.",2016 Aug 19,"['Agrawal, Anurodh Shankar', 'Ying, Tianlei', 'Tao, Xinrong', 'Garron, Tania', 'Algaissi, Abdullah', 'Wang, Yanping', 'Wang, Lili', 'Peng, Bi-Hung', 'Jiang, Shibo', 'Dimitrov, Dimiter S.', 'Tseng, Chien-Te K.']",Sci Rep,,,True
1b8770691fe974dfb269a16db59750370b9c0c21,PMC,Epidemiology and etiology of influenza-like-illness in households in Vietnam; it’s not all about the kids!,http://dx.doi.org/10.1016/j.jcv.2016.07.014,PMC4994428,27479176,CC BY,"BACKGROUND: Household studies provide opportunities to understand influenza-like-illness (ILI) transmission, but data from (sub)tropical developing countries are scarce. OBJECTIVE: To determine the viral etiology and epidemiology of ILI in households. STUDY DESIGN: ILI was detected by active case finding amongst a cohort of 263 northern Vietnam households between 2008 and 2013. Health workers collected nose and throat swabs for virus detection by multiplex real-time RT-PCR. RESULTS: ILI was detected at least once in 219 (23.7%) of 945 household members. 271 (62.3%) of 435 nose/throat swabs were positive for at least one of the 15 viruses tested. Six viruses predominated amongst positive swabs: Rhinovirus (28%), Influenza virus (17%), Coronavirus (8%), Enterovirus (5%), Respiratory syncytial virus (3%), Metapneumovirus virus (2.5%) and Parainfluenza virus 3 (1.8%). There was no clear seasonality, but 78% of episodes occurred in Winter/Spring for Influenza compared to 32% for Rhinovirus. Participants, on average, suffered 0.49 ILI, and 0.29 virus-positive ILI episodes, with no significant effects of gender, age, or household size. In contrast to US and Australian community studies, the frequency of ILI decreased as the number of household members aged below 5 years increased (p = 0.006). CONCLUSION: The findings indicate the need for tailored ILI control strategies, and for better understanding of how local childcare practices and seasonality may influence transmission and the role of children.",2016 Sep,"['Nguyen, Diep Ngoc Thi', 'Mai, Le Quynh', 'Bryant, Juliet E.', 'Hang, Nguyen Le Khanh', 'Hoa, Le Nguyen Minh', 'Nadjm, Behzad', 'Thai, Pham Quang', 'Duong, Tran Nhu', 'Anh, Dang Duc', 'Horby, Peter', 'van Doorn, H. Rogier', 'Wertheim, Heiman F.L.', 'Fox, Annette']",J Clin Virol,,,False
b285ac5faca47fd0d835d385a193bb169447015f,PMC,TGEV infection up-regulates FcRn expression via activation of NF-κB signaling,http://dx.doi.org/10.1038/srep32154,PMC4995372,27555521,CC BY,"It has been well characterized that the neonatal Fc receptor (FcRn) transports maternal IgG to a fetus or newborn and protects IgG from degradation. We previously reported that FcRn is expressed in a model of normal porcine intestinal epithelial cells (IPEC-J2). Transmissible gastroenteritis is an acute enteric disease of swine that is caused by transmissible gastroenteritis virus (TGEV). How porcine FcRn (pFcRn) expression is regulated by pathogenic infection remains unknown. Our research shows that IPEC-J2 cells infected with TGEV had up-regulated pFcRn expression. In addition, the NF-κB signaling pathway was activated in IPEC-J2 cells by TGEV infection. Furthermore, treatment of TGEV-infected IPEC-J2 cells with the NF-κB-specific inhibitor BAY 11-7082 resulted in down-regulation of pFcRn expression. Transient transfection of pFcRn promoter luciferase report plasmids with overexpression of NF-κB p65 transcription factor enhanced the activation of the luciferase report plasmids. We identified four NF-κB transcription factor binding sites in the promoter region of this gene using luciferase reporter system, chromatin immunoprecipitation, electromobility shift assay, and supershift analysis. Together, the data provide the first evidence that TGEV infection up-regulates pFcRn expression via activation of NF-κB signaling.",2016 Aug 24,"['Guo, Jinyue', 'Li, Fei', 'Qian, Shaoju', 'Bi, Dingren', 'He, Qigai', 'Jin, Hui', 'Luo, Rui', 'Li, Shaowen', 'Meng, Xianrong', 'Li, Zili']",Sci Rep,,,True
73d0e03660b35119807acf6aafc33dc2276f19a2,PMC,TGEV infection up-regulates FcRn expression via activation of NF-κB signaling,http://dx.doi.org/10.1038/srep32154,PMC4995372,27555521,CC BY,"It has been well characterized that the neonatal Fc receptor (FcRn) transports maternal IgG to a fetus or newborn and protects IgG from degradation. We previously reported that FcRn is expressed in a model of normal porcine intestinal epithelial cells (IPEC-J2). Transmissible gastroenteritis is an acute enteric disease of swine that is caused by transmissible gastroenteritis virus (TGEV). How porcine FcRn (pFcRn) expression is regulated by pathogenic infection remains unknown. Our research shows that IPEC-J2 cells infected with TGEV had up-regulated pFcRn expression. In addition, the NF-κB signaling pathway was activated in IPEC-J2 cells by TGEV infection. Furthermore, treatment of TGEV-infected IPEC-J2 cells with the NF-κB-specific inhibitor BAY 11-7082 resulted in down-regulation of pFcRn expression. Transient transfection of pFcRn promoter luciferase report plasmids with overexpression of NF-κB p65 transcription factor enhanced the activation of the luciferase report plasmids. We identified four NF-κB transcription factor binding sites in the promoter region of this gene using luciferase reporter system, chromatin immunoprecipitation, electromobility shift assay, and supershift analysis. Together, the data provide the first evidence that TGEV infection up-regulates pFcRn expression via activation of NF-κB signaling.",2016 Aug 24,"['Guo, Jinyue', 'Li, Fei', 'Qian, Shaoju', 'Bi, Dingren', 'He, Qigai', 'Jin, Hui', 'Luo, Rui', 'Li, Shaowen', 'Meng, Xianrong', 'Li, Zili']",Sci Rep,,,False
7a32e94a4c479957e6c98108ac3eaa344bc07f7d,PMC,The rise and fall of infectious disease in a warmer world,http://dx.doi.org/10.12688/f1000research.8766.1,PMC4995683,27610227,CC BY,"Now-outdated estimates proposed that climate change should have increased the number of people at risk of malaria, yet malaria and several other infectious diseases have declined. Although some diseases have increased as the climate has warmed, evidence for widespread climate-driven disease expansion has not materialized, despite increased research attention. Biological responses to warming depend on the non-linear relationships between physiological performance and temperature, called the thermal response curve. This leads performance to rise and fall with temperature. Under climate change, host species and their associated parasites face extinction if they cannot either thermoregulate or adapt by shifting phenology or geographic range. Climate change might also affect disease transmission through increases or decreases in host susceptibility and infective stage (and vector) production, longevity, and pathology. Many other factors drive disease transmission, especially economics, and some change in time along with temperature, making it hard to distinguish whether temperature drives disease or just correlates with disease drivers. Although it is difficult to predict how climate change will affect infectious disease, an ecological approach can help meet the challenge.",2016 Aug 19,"['Lafferty, Kevin D.', 'Mordecai, Erin A.']",F1000Res,,,True
2e26e0f3a9c4729b7f8aedcd9a95b00257378e20,PMC,A Subset of Protective γ(9)δ(2) T Cells Is Activated by Novel Mycobacterial Glycolipid Components,http://dx.doi.org/10.1128/IAI.01322-15,PMC4995917,27297390,CC BY,"γ(9)δ(2) T cells provide a natural bridge between innate and adaptive immunity, rapidly and potently respond to pathogen infection in mucosal tissues, and are prominently induced by both tuberculosis (TB) infection and bacillus Calmette Guérin (BCG) vaccination. Mycobacterium-expanded γ(9)δ(2) T cells represent only a subset of the phosphoantigen {isopentenyl pyrophosphate [IPP] and (E)-4-hydroxy-3-methyl-but-2-enylpyrophosphate [HMBPP]}-responsive γ(9)δ(2) T cells, expressing an oligoclonal set of T cell receptor (TCR) sequences which more efficiently recognize and inhibit intracellular Mycobacterium tuberculosis infection. Based on this premise, we have been searching for M. tuberculosis antigens specifically capable of inducing a unique subset of mycobacterium-protective γ(9)δ(2) T cells. Our screening strategy includes the identification of M. tuberculosis fractions that expand γ(9)δ(2) T cells with biological functions capable of inhibiting intracellular mycobacterial replication. Chemical treatments of M. tuberculosis whole-cell lysates (MtbWL) ruled out protein, nucleic acid, and nonpolar lipids as the M. tuberculosis antigens inducing protective γ(9)δ(2) T cells. Mild acid hydrolysis, which transforms complex carbohydrate to monomeric residues, abrogated the specific activity of M. tuberculosis whole-cell lysates, suggesting that a polysaccharide was required for biological activity. Extraction of MtbWL with chloroform-methanol-water (10:10:3) resulted in a polar lipid fraction with highly enriched specific activity; this activity was further enriched by silica gel chromatography. A combination of mass spectrometry and nuclear magnetic resonance analysis of bioactive fractions indicated that 6-O-methylglucose-containing lipopolysaccharides (mGLP) are predominant components present in this active fraction. These results have important implications for the development of new immunotherapeutic approaches for prevention and treatment of TB.",2016 Aug 19,"['Xia, Mei', 'Hesser, Danny C.', 'De, Prithwiraj', 'Sakala, Isaac G.', 'Spencer, Charles T.', 'Kirkwood, Jay S.', 'Abate, Getahun', 'Chatterjee, Delphi', 'Dobos, Karen M.', 'Hoft, Daniel F.']",Infect Immun,,,False
f030f518075c344748867210874ab67ffd02259e,PMC,A Subset of Protective γ(9)δ(2) T Cells Is Activated by Novel Mycobacterial Glycolipid Components,http://dx.doi.org/10.1128/IAI.01322-15,PMC4995917,27297390,CC BY,"γ(9)δ(2) T cells provide a natural bridge between innate and adaptive immunity, rapidly and potently respond to pathogen infection in mucosal tissues, and are prominently induced by both tuberculosis (TB) infection and bacillus Calmette Guérin (BCG) vaccination. Mycobacterium-expanded γ(9)δ(2) T cells represent only a subset of the phosphoantigen {isopentenyl pyrophosphate [IPP] and (E)-4-hydroxy-3-methyl-but-2-enylpyrophosphate [HMBPP]}-responsive γ(9)δ(2) T cells, expressing an oligoclonal set of T cell receptor (TCR) sequences which more efficiently recognize and inhibit intracellular Mycobacterium tuberculosis infection. Based on this premise, we have been searching for M. tuberculosis antigens specifically capable of inducing a unique subset of mycobacterium-protective γ(9)δ(2) T cells. Our screening strategy includes the identification of M. tuberculosis fractions that expand γ(9)δ(2) T cells with biological functions capable of inhibiting intracellular mycobacterial replication. Chemical treatments of M. tuberculosis whole-cell lysates (MtbWL) ruled out protein, nucleic acid, and nonpolar lipids as the M. tuberculosis antigens inducing protective γ(9)δ(2) T cells. Mild acid hydrolysis, which transforms complex carbohydrate to monomeric residues, abrogated the specific activity of M. tuberculosis whole-cell lysates, suggesting that a polysaccharide was required for biological activity. Extraction of MtbWL with chloroform-methanol-water (10:10:3) resulted in a polar lipid fraction with highly enriched specific activity; this activity was further enriched by silica gel chromatography. A combination of mass spectrometry and nuclear magnetic resonance analysis of bioactive fractions indicated that 6-O-methylglucose-containing lipopolysaccharides (mGLP) are predominant components present in this active fraction. These results have important implications for the development of new immunotherapeutic approaches for prevention and treatment of TB.",2016 Aug 19,"['Xia, Mei', 'Hesser, Danny C.', 'De, Prithwiraj', 'Sakala, Isaac G.', 'Spencer, Charles T.', 'Kirkwood, Jay S.', 'Abate, Getahun', 'Chatterjee, Delphi', 'Dobos, Karen M.', 'Hoft, Daniel F.']",Infect Immun,,,True
48bd5f768f3464ac253a120d2eddeb89c323f324,PMC,"Integrated Microfluidic Nucleic Acid Isolation, Isothermal Amplification, and Amplicon Quantification",http://dx.doi.org/10.3390/microarrays4040474,PMC4996405,27600235,CC BY,"Microfluidic components and systems for rapid (<60 min), low-cost, convenient, field-deployable sequence-specific nucleic acid-based amplification tests (NAATs) are described. A microfluidic point-of-care (POC) diagnostics test to quantify HIV viral load from blood samples serves as a representative and instructive example to discuss the technical issues and capabilities of “lab on a chip” NAAT devices. A portable, miniaturized POC NAAT with performance comparable to conventional PCR (polymerase-chain reaction)-based tests in clinical laboratories can be realized with a disposable, palm-sized, plastic microfluidic chip in which: (1) nucleic acids (NAs) are extracted from relatively large (~mL) volume sample lysates using an embedded porous silica glass fiber or cellulose binding phase (“membrane”) to capture sample NAs in a flow-through, filtration mode; (2) NAs captured on the membrane are isothermally (~65 °C) amplified; (3) amplicon production is monitored by real-time fluorescence detection, such as with a smartphone CCD camera serving as a low-cost detector; and (4) paraffin-encapsulated, lyophilized reagents for temperature-activated release are pre-stored in the chip. Limits of Detection (LOD) better than 10(3) virons/sample can be achieved. A modified chip with conduits hosting a diffusion-mode amplification process provides a simple visual indicator to readily quantify sample NA template. In addition, a companion microfluidic device for extracting plasma from whole blood without a centrifuge, generating cell-free plasma for chip-based molecular diagnostics, is described. Extensions to a myriad of related applications including, for example, food testing, cancer screening, and insect genotyping are briefly surveyed.",2015 Oct 20,"['Mauk, Michael G.', 'Liu, Changchun', 'Song, Jinzhao', 'Bau, Haim H.']",Microarrays (Basel),,,True
78c82f8e3198d5c95cbbcceabefddbe82e8f2442,PMC,"Prioritization of Zoonotic Diseases in Kenya, 2015",http://dx.doi.org/10.1371/journal.pone.0161576,PMC4996421,27557120,CC0,"INTRODUCTION: Zoonotic diseases have varying public health burden and socio-economic impact across time and geographical settings making their prioritization for prevention and control important at the national level. We conducted systematic prioritization of zoonotic diseases and developed a ranked list of these diseases that would guide allocation of resources to enhance their surveillance, prevention, and control. METHODS: A group of 36 medical, veterinary, and wildlife experts in zoonoses from government, research institutions and universities in Kenya prioritized 36 diseases using a semi-quantitative One Health Zoonotic Disease Prioritization tool developed by Centers for Disease Control and Prevention with slight adaptations. The tool comprises five steps: listing of zoonotic diseases to be prioritized, development of ranking criteria, weighting criteria by pairwise comparison through analytical hierarchical process, scoring each zoonotic disease based on the criteria, and aggregation of scores. RESULTS: In order of importance, the participants identified severity of illness in humans, epidemic/pandemic potential in humans, socio-economic burden, prevalence/incidence and availability of interventions (weighted scores assigned to each criteria were 0.23, 0.22, 0.21, 0.17 and 0.17 respectively), as the criteria to define the relative importance of the diseases. The top five priority diseases in descending order of ranking were anthrax, trypanosomiasis, rabies, brucellosis and Rift Valley fever. CONCLUSION: Although less prominently mentioned, neglected zoonotic diseases ranked highly compared to those with epidemic potential suggesting these endemic diseases cause substantial public health burden. The list of priority zoonotic disease is crucial for the targeted allocation of resources and informing disease prevention and control programs for zoonoses in Kenya.",2016 Aug 24,"['Munyua, Peninah', 'Bitek, Austine', 'Osoro, Eric', 'Pieracci, Emily G.', 'Muema, Josephat', 'Mwatondo, Athman', 'Kungu, Mathew', 'Nanyingi, Mark', 'Gharpure, Radhika', 'Njenga, Kariuki', 'Thumbi, Samuel M.']",PLoS One,,,True
1d6e09ce2559ff9fcb55f3351110880446b477fe,PMC,Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements,http://dx.doi.org/10.1371/journal.pntd.0004921,PMC4996428,27556644,CC BY,"BACKGROUND: There are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses) replication. METHODOLOGY/PRINCIPAL FINDINGS: Seventy-nine novel RNA binding proteins for dengue virus (DENV) were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated. CONCLUSIONS/SIGNIFICANCE: The method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with DENV and reveals how DENV modulates and usurps cellular proteins for efficient amplification.",2016 Aug 24,"['Viktorovskaya, Olga V.', 'Greco, Todd M.', 'Cristea, Ileana M.', 'Thompson, Sunnie R.']",PLoS Negl Trop Dis,,,True
60f0773c8eeace01dd0364c5c63febbfe9dd3a62,PMC,Impact of LbSapSal Vaccine in Canine Immunological and Parasitological Features before and after Leishmania chagasi-Challenge,http://dx.doi.org/10.1371/journal.pone.0161169,PMC4996460,27556586,CC BY,"Dogs represent the most important domestic reservoir of L. chagasi (syn. L. infantum). A vaccine against canine visceral leishmaniasis (CVL) would be an important tool for decreasing the anxiety related to possible L. chagasi infection and for controlling human visceral leishmaniasis (VL). Because the sand fly salivary proteins are potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in past decades. We investigated the immunogenicity of the “LbSapSal” vaccine (L. braziliensis antigens, saponin as adjuvant, and Lutzomyia longipalpis salivary gland extract) in dogs at baseline (T(0)), during the post-vaccination protocol (T(3rd)) and after early (T(90)) and late (T(885)) times following L. chagasi-challenge. Our major data indicated that immunization with “LbSapSal” is able to induce biomarkers characterized by enhanced amounts of type I (tumor necrosis factor [TNF]-α, interleukin [IL]-12, interferon [IFN]-γ) cytokines and reduction in type II cytokines (IL-4 and TGF-β), even after experimental challenge. The establishment of a prominent pro-inflammatory immune response after “LbSapSal” immunization supported the increased levels of nitric oxide production, favoring a reduction in spleen parasitism (78.9%) and indicating long-lasting protection against L. chagasi infection. In conclusion, these results confirmed the hypothesis that the “LbSapSal” vaccination is a potential tool to control the Leishmania chagasi infection.",2016 Aug 24,"['Resende, Lucilene Aparecida', 'Aguiar-Soares, Rodrigo Dian de Oliveira', 'Gama-Ker, Henrique', 'Roatt, Bruno Mendes', 'de Mendonça, Ludmila Zanandreis', 'Alves, Marina Luiza Rodrigues', 'da Silveira-Lemos, Denise', 'Corrêa-Oliveira, Rodrigo', 'Martins-Filho, Olindo Assis', 'Araújo, Márcio Sobreira Silva', 'Fujiwara, Ricardo Toshio', 'Gontijo, Nelder Figueiredo', 'Reis, Alexandre Barbosa', 'Giunchetti, Rodolfo Cordeiro']",PLoS One,,,True
7aa69b98902425b5daeb3b1f647d067b8abf7157,PMC,"National Library of Medicine Disaster Information Management Research Center: Achieving the vision, 2010–2013",http://dx.doi.org/10.3233/ISU-140731,PMC4996476,27570333,CC BY,"From 2010 to 2013, the National Library of Medicine (NLM) Disaster Information Management Research Center (DIMRC) continued to build its programs and services on the foundation laid in its starting years, 2008–2010. Prior to 2008, NLM had a long history of providing health information, training, and tools in response to disasters. Aware of this legacy, the NLM long range plan (Charting a Course for the 21st Century: NLM’s Long Range Plan 2006–2016) called for creation of a center to show “a strong commitment to disaster remediation and to provide a platform for demonstrating how libraries and librarians can be part of the solution to this national problem”. NLM is continuing efforts to ensure that medical libraries have plans for the continuity of their operations, librarians are trained to understand their roles in preparedness and response, online disaster health information resources are available for many audiences and in multiple formats, and research is conducted on tools to enhance the exchange of critical information during and following disasters. This paper describes the 2010–2013 goals and activities of DIMRC and its future plans.",2014,"['Love, Cynthia B.', 'Arnesen, Stacey J.', 'Phillips, Steven J.', 'Windom, Robert E.']",Inf Serv Use,,,True
7b9a303570b221251e6281e20f70ecaa125c4e78,PMC,Expression of the NS5 (VPg) Protein of Murine Norovirus Induces a G1/S Phase Arrest,http://dx.doi.org/10.1371/journal.pone.0161582,PMC4996510,27556406,CC BY,"Murine norovirus-1 (MNV-1) is known to subvert host cell division inducing an accumulation of cells in the G(0)/G(1) phase, creating conditions where viral replication is favored. This study identified that NS5 (VPg), is capable of inducing cell cycle arrest in the absence of viral replication or other viral proteins in an analogous manner to MNV-1 infection. NS5 expression induced an accumulation of cells in the G(0)/G(1) phase in an asynchronous population by inhibiting progression at the G(1)/S restriction point. Furthermore, NS5 expression resulted in a down-regulation of cyclin A expression in asynchronous cells and inhibited cyclin A expression in cells progressing from G(1) to S phase. The activity of NS5 on the host cell cycle occurs through an uncharacterized function. Amino acid substitutions of NS5(Y26A) and NS5(F123A) that inhibit the ability for NS5 to attach to RNA and recruit host eukaryotic translation initiation factors, respectively, retained the ability to induce an accumulation of cells in the G(0)/G(1) phase as identified for wild-type NS5. To the best of our knowledge, this is the first report of a VPg protein manipulating the host cell cycle.",2016 Aug 24,"['Davies, Colin', 'Ward, Vernon K.']",PLoS One,,,True
417286ac22fc95bdfe96df0dc2a7c1e3eb5befe1,PMC,Evaluation of Low versus High Volume per Minute Displacement CO(2) Methods of Euthanasia in the Induction and Duration of Panic-Associated Behavior and Physiology,http://dx.doi.org/10.3390/ani6080045,PMC4997270,27490573,CC BY,"SIMPLE SUMMARY: Current recommendations for the use of CO(2) as a euthanasia agent for rats require the use of gradual fill methods in order to render the animal insensible prior to their experience of pain. However, there is concern that the use of these gradual fill methods may increase the distress experienced by these animals. We evaluated social and anxiety behavior of rats that had been exposed to concentrations of CO(2) that did not cause a loss of consciousness. We also evaluated the physiologic changes of rats that were euthanized with gradual fill protocols as compared to rapid fill methods. We found that rats exposed to concentrations of CO(2) that did not cause a loss of consciousness did exhibit increased anxiety and decreased social behavior. We also found that the use of a 10% volume per minute displacement rate of CO(2) resulted in physiologic and behavioral changes suggestive of distress. ABSTRACT: Current recommendations for the use of CO(2) as a euthanasia agent for rats require the use of gradual fill protocols (such as 10% to 30% volume displacement per minute) in order to render the animal insensible prior to exposure to levels of CO(2) that are associated with pain. However, exposing rats to CO(2), concentrations as low as 7% CO(2) are reported to cause distress and 10%–20% CO(2) induces panic-associated behavior and physiology, but loss of consciousness does not occur until CO(2) concentrations are at least 40%. This suggests that the use of the currently recommended low flow volume per minute displacement rates create a situation where rats are exposed to concentrations of CO(2) that induce anxiety, panic, and distress for prolonged periods of time. This study first characterized the response of male rats exposed to normoxic 20% CO(2) for a prolonged period of time as compared to room air controls. It demonstrated that rats exposed to this experimental condition displayed clinical signs consistent with significantly increased panic-associated behavior and physiology during CO(2) exposure. When atmospheric air was then again delivered, there was a robust increase in respiration rate that coincided with rats moving to the air intake. The rats exposed to CO(2) also displayed behaviors consistent with increased anxiety in the behavioral testing that followed the exposure. Next, this study assessed the behavioral and physiologic responses of rats that were euthanized with 100% CO(2) infused at 10%, 30%, or 100% volume per minute displacement rates. Analysis of the concentrations of CO(2) and oxygen in the euthanasia chamber and the behavioral responses of the rats suggest that the use of the very low flow volume per minute displacement rate (10%) may prolong the duration of panicogenic ranges of ambient CO(2), while the use of the higher flow volume per minute displacement rate (100%) increases agitation. Therefore, of the volume displacement per minute rates evaluated, this study suggests that 30% minimizes the potential pain and distress experienced by the animal.",2016 Aug 2,"['Hickman, Debra L.', 'Fitz, Stephanie D.', 'Bernabe, Cristian S.', 'Caliman, Izabela F.', 'Haulcomb, Melissa M.', 'Federici, Lauren M.', 'Shekhar, Anantha', 'Johnson, Philip L.']",Animals (Basel),,,True
f8f5d842db3bc80e5c22011583b8e965abfe624c,PMC,Chinese Public Attention to the Outbreak of Ebola in West Africa: Evidence from the Online Big Data Platform,http://dx.doi.org/10.3390/ijerph13080780,PMC4997466,27527196,CC BY,"Objective: The outbreak of the Ebola epidemic in West Africa in 2014 exerted enormous global public reaction via the Internet and social media. This study aimed to investigate and evaluate the public reaction to Ebola in China and identify the primitive correlation between possible influence factors caused by the outbreak of Ebola in West Africa and Chinese public attention via Internet surveillance. Methods: Baidu Index (BDI) and Sina Micro Index (SMI) were collected from their official websites, and the disease-related data were recorded from the websites of the World Health Organization (WHO), U.S. Centers for Disease Control and Prevention (CDC), and U.S. National Ministries of Health. The average BDI of Internet users in different regions were calculated to identify the public reaction to the Ebola outbreak. Spearman’s rank correlation was used to check the relationship of epidemic trends with BDI and SMI. Additionally, spatio-temporal analysis and autocorrelation analysis were performed to detect the clustered areas with the high attention to the topic of “Ebola”. The related news reports were collected from authoritative websites to identify potential patterns. Results: The BDI and the SMI for “Ebola” showed a similar fluctuating trend with a correlation coefficient = 0.9 (p < 0.05). The average BDI in Beijing, Tibet, and Shanghai was higher than other cities. However, the disease-related indicators did not identify potential correlation with both indices above. A hotspot area was detected in Tibet by local autocorrelation analysis. The most likely cluster identified by spatiotemporal cluster analysis was in the northeast regions of China with the relative risk (RR) of 2.26 (p ≤ 0.01) from 30 July to 14 August in 2014. Qualitative analysis indicated that negative news could lead to a continuous increase of the public’s attention until the appearance of a positive news report. Conclusions: Confronted with the risk of cross-border transmission of the infectious disease, online surveillance might be used as an innovative approach to perform public communication and health education through examining the public’s reaction and attitude.",2016 Aug 3,"['Liu, Kui', 'Li, Li', 'Jiang, Tao', 'Chen, Bin', 'Jiang, Zhenggang', 'Wang, Zhengting', 'Chen, Yongdi', 'Jiang, Jianmin', 'Gu, Hua']",Int J Environ Res Public Health,,,True
f243e05a2d51029218e0c313b20fa57c65104a62,PMC,Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications,http://dx.doi.org/10.3390/v8080206,PMC4997570,27490565,CC BY,"The 2014 outbreak of Ebola virus (EBOV) in Western Africa highlighted the need for anti-EBOV therapeutics. Clomiphene is a U.S. Food and Drug Administration (FDA)-approved drug that blocks EBOV entry and infection in cells and significantly protects EBOV-challenged mice. As provided, clomiphene is, approximately, a 60:40 mixture of two stereoisomers, enclomiphene and zuclomiphene. The pharmacokinetic properties of the two isomers vary, but both accumulate in the eye and male reproductive tract, tissues in which EBOV can persist. Here we compared the ability of clomiphene and its isomers to inhibit EBOV using viral-like particle (VLP) entry and transcription/replication-competent VLP (trVLP) assays. Clomiphene and its isomers inhibited the entry and infection of VLPs and trVLPs with similar potencies. This was demonstrated with VLPs bearing the glycoproteins from three filoviruses (EBOV Mayinga, EBOV Makona, and Marburg virus) and in two cell lines (293T/17 and Vero E6). Visual problems have been noted in EBOV survivors, and viral RNA has been isolated from semen up to nine months post-infection. Since the clomiphene isomers accumulate in these affected tissues, clomiphene or one of its isomers warrants consideration as an anti-EBOV agent, for example, to potentially help ameliorate symptoms in EBOV survivors.",2016 Aug 2,"['Nelson, Elizabeth A.', 'Barnes, Alyson B.', 'Wiehle, Ronald D.', 'Fontenot, Gregory K.', 'Hoenen, Thomas', 'White, Judith M.']",Viruses,,,True
b4609f3760031ac126473d8438bdebc4df596be0,PMC,"Inoculation of Goats, Sheep, and Horses with MERS-CoV Does Not Result in Productive Viral Shedding",http://dx.doi.org/10.3390/v8080230,PMC4997592,27548203,CC BY,"The Middle East respiratory syndrome coronavirus (MERS-CoV) was first recognized in 2012 and can cause severe disease in infected humans. Dromedary camels are the reservoir for the virus, although, other than nasal discharge, these animals do not display any overt clinical disease. Data from in vitro experiments suggest that other livestock such as sheep, goats, and horses might also contribute to viral transmission, although field data has not identified any seropositive animals. In order to understand if these animals could be infected, we challenged young goats and horses and adult sheep with MERS-CoV by intranasal inoculation. Minimal or no virus shedding was detected in all of the animals. During the four weeks following inoculation, neutralizing antibodies were detected in the young goats, but not in sheep or horses.",2016 Aug 19,"['Adney, Danielle R.', 'Brown, Vienna R.', 'Porter, Stephanie M.', 'Bielefeldt-Ohmann, Helle', 'Hartwig, Airn E.', 'Bowen, Richard A.']",Viruses,,,True
7bfb902f2434b4667d48f2fcb5a1d7233acda4c5,PMC,Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells,http://dx.doi.org/10.1038/srep32288,PMC4997611,27558873,CC BY,"Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre. In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown. Here we found that active CHIKV infection stimulated production of MCP-1 in monocytes. Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection. Indeed, blocking interferon-α/β receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production. Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection. In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFNβ in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection.",2016 Aug 25,"['Ruiz Silva, Mariana', 'van der Ende-Metselaar, Heidi', 'Mulder, H. Lie', 'Smit, Jolanda M.', 'Rodenhuis-Zybert, Izabela A.']",Sci Rep,,,True
c10cefdc314bbd0702d8d8ced268caad9ae818fb,PMC,Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells,http://dx.doi.org/10.1038/srep32288,PMC4997611,27558873,CC BY,"Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre. In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown. Here we found that active CHIKV infection stimulated production of MCP-1 in monocytes. Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection. Indeed, blocking interferon-α/β receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production. Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection. In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFNβ in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection.",2016 Aug 25,"['Ruiz Silva, Mariana', 'van der Ende-Metselaar, Heidi', 'Mulder, H. Lie', 'Smit, Jolanda M.', 'Rodenhuis-Zybert, Izabela A.']",Sci Rep,,,False
be9cb78bf2453f68b260e9ed4f75d9ceccb77754,PMC,Lower serum uric acid level predicts mortality in dialysis patients,http://dx.doi.org/10.1097/MD.0000000000003701,PMC4998435,27310949,CC BY,"We evaluated the impact of serum uric acid (SUA) on mortality in patients with chronic dialysis. A total of 4132 adult patients on dialysis were enrolled prospectively between August 2008 and September 2014. Among them, we included 1738 patients who maintained dialysis for at least 3 months and had available SUA in the database. We categorized the time averaged-SUA (TA-SUA) into 5 groups: <5.5, 5.5–6.4, 6.5–7.4, 7.5–8.4, and ≥8.5 mg/dL. Cox regression analysis was used to calculate the hazard ratio (HR) of all-cause mortality according to SUA group. The mean TA-SUA level was slightly higher in men than in women. Patients with lower TA-SUA level tended to have lower body mass index (BMI), phosphorus, serum albumin level, higher proportion of diabetes mellitus (DM), and higher proportion of malnourishment on the subjective global assessment (SGA). During a median follow-up of 43.9 months, 206 patients died. Patients with the highest SUA had a similar risk to the middle 3 TA-SUA groups, but the lowest TA-SUA group had a significantly elevated HR for mortality. The lowest TA-SUA group was significantly associated with increased all-cause mortality (adjusted HR, 1.720; 95% confidence interval, 1.007–2.937; P = 0.047) even after adjusting for demographic, comorbid, nutritional covariables, and medication use that could affect SUA levels. This association was prominent in patients with well nourishment on the SGA, a preserved serum albumin level, a higher BMI, and concomitant DM although these parameters had no significant interaction in the TA-SUA-mortality relationship except DM. In conclusion, a lower TA-SUA level <5.5 mg/dL predicted all-cause mortality in patients with chronic dialysis.",2016 Jun 17,"['Bae, Eunjin', 'Cho, Hyun-Jeong', 'Shin, Nara', 'Kim, Sun Moon', 'Yang, Seung Hee', 'Kim, Dong Ki', 'Kim, Yong-Lim', 'Kang, Shin-Wook', 'Yang, Chul Woo', 'Kim, Nam Ho', 'Kim, Yon Su', 'Lee, Hajeong']",Medicine (Baltimore),,,True
8602709a812146a012e16df450b991f6343d2f46,PMC,Suppression of Virulent Porcine Epidemic Diarrhea Virus Proliferation by the PI3K/Akt/GSK-3α/β Pathway,http://dx.doi.org/10.1371/journal.pone.0161508,PMC4999130,27560518,CC BY,"Porcine epidemic diarrhea virus (PEDV) has recently caused high mortality in suckling piglets with subsequent large economic losses to the swine industry. Many intracellular signaling pathways, including the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, are activated by viral infection. The PI3K/Akt pathway is an important cellular pathway that has been shown to be required for virus replication. In the present study, we found that the PEDV JS-2013 strain activated Akt in Vero cells at early (5–15 min) and late stages (8–10 h) of infection. Inhibiting PI3K, an upstream activator of Akt, enhanced PEDV replication. Inhibiting GSK-3α/β, one of the downstream effectors of PI3K/Akt pathway and regulated by Akt during PEDV infected Vero cells, also enhanced PEDV replication. Collectively, our data suggest that PI3K/Akt/GSK-3α/β signaling pathway is activated by PEDV and functions in inhibiting PEDV replication.",2016 Aug 25,"['Kong, Ning', 'Wu, Yongguang', 'Meng, Qiong', 'Wang, Zhongze', 'Zuo, Yewen', 'Pan, Xi', 'Tong, Wu', 'Zheng, Hao', 'Li, Guoxin', 'Yang, Shen', 'Yu, Hai', 'Zhou, En-min', 'Shan, Tongling', 'Tong, Guangzhi']",PLoS One,,,True
9ef23d86bba041d9fc573624cdf17e94a30fb8f6,PMC,"Molecular epidemiology and characterization of human coronavirus in Thailand, 2012–2013",http://dx.doi.org/10.1186/s40064-016-3101-9,PMC4999384,27625974,CC BY,"BACKGROUND: Coronavirus causes respiratory infections in humans. To determine the prevalence of human coronavirus (HCoV) infection among patients with influenza-like illness, 5833 clinical samples from nasopharyngeal swabs and aspirates collected between January 2012 and December 2013 were examined. RESULTS: HCoV was found in 46 (0.79 %) samples. There were 19 (0.32 %) HCoV-HKU1, 19 (0.32 %) HCoV-NL63, 5 (0.09 %) HCoV-229E, and 3 (0.05 %) HCoV-OC43. None of the sample tested positive for MERS-CoV. The majority (54 %) of the HCoV-positive patients were between the ages of 0 and 5 years. HCoV was detected throughout the 2-year period and generally peaked from May to October, which coincided with the rainy season. Phylogenetic trees based on the alignment of the spike (S) gene sequences suggest an emergence of a new clade for HCoV-229E. CONCLUSIONS: The data in this study provide an insight into the prevalence of the recent circulating HCoVs in the region.",2016 Aug 26,"['Soonnarong, Rapeepun', 'Thongpan, Ilada', 'Payungporn, Sunchai', 'Vuthitanachot, Chanpim', 'Vuthitanachot, Viboonsuk', 'Vichiwattana, Preeyaporn', 'Vongpunsawad, Sompong', 'Poovorawan, Yong']",Springerplus,,,True
74de948d0adbf472ee959b8521f40fb4a5aa034a,PMC,Moonshot Science—Risks and Benefits,http://dx.doi.org/10.1128/mBio.01381-16,PMC4999558,27578761,CC BY,"Ever since the successful Apollo 11 Moon landing in 1969, a “moonshot” has come to signify a bold effort to achieve a seemingly impossible task. The Obama administration recently called for a moonshot to cure cancer, an initiative that has elicited mixed responses from researchers who welcome additional funding but worry about raising expectations. We suggest that a successful moonshot requires a sufficient understanding of the basic science underlying a problem in question so that efforts can be focused on engineering a solution. Current gaps in our basic knowledge of cancer biology make the cancer moonshot a uniquely challenging endeavor. Nevertheless, history has shown that intensive research efforts have frequently yielded conceptual and technological breakthroughs with unanticipated benefits for society. We expect that this effort will be no different.",2016 Aug 30,"['Casadevall, Arturo', 'Fang, Ferric C.']",mBio,,,True
ec0b7ac5c69486b4c914cf362fc49e176f401516,PMC,CD8 T Cell–Independent Antitumor Response and Its Potential for Treatment of Malignant Gliomas,http://dx.doi.org/10.3390/cancers8080071,PMC4999780,27472363,CC BY,"Malignant brain tumors continue to represent a devastating diagnosis with no real chance for cure. Despite an increasing list of potential salvage therapies, standard-of-care for these patients has not changed in over a decade. Immunotherapy has been seen as an exciting option, with the potential to offer specific and long lasting tumor clearance. The “gold standard” in immunotherapy has been the development of a tumor-specific CD8 T cell response to potentiate tumor clearance and immunological memory. While many advances have been made in the field of immunotherapy, few therapies have seen true success. Many of the same principles used to develop immunotherapy in tumors of the peripheral organs have been applied to brain tumor immunotherapy. The immune-specialized nature of the brain should call into question whether this approach is appropriate. Recent results from our own experiments require a rethinking of current dogma. Perhaps a CD8 T cell response is not sufficient for an organ as immunologically unique as the brain. Examination of previously elucidated principles of the brain’s immune-specialized status and known immunological preferences should generate discussion and experimentation to address the failure of current therapies.",2016 Jul 27,"['Murphy, Katherine A.', 'Griffith, Thomas S.']",Cancers (Basel),,,True
3691c1e9130028008093d3d62e16a43883631cae,PMC,An Old Solution for a New Problem: Antiserum against Emerging Infectious Diseases,http://dx.doi.org/10.3389/fpubh.2016.00178,PMC5000394,27617259,CC BY,,2016 Aug 26,"Morais, Victor",Front Public Health,,,True
caadc408ff1144a53369c7e0f63634ff264be9ee,PMC,Evaluation of a new community-based curriculum in disaster medicine for undergraduates,http://dx.doi.org/10.1186/s12909-016-0746-6,PMC5000399,27562428,CC BY,"BACKGROUND: Nowadays, many medical schools include training in disaster medicine in undergraduate studies. This study evaluated the efficacy of a disaster medicine curriculum recently designed for Saudi Arabian medical students. METHODS: Participants were 15 male and 14 female students in their fourth, fifth or sixth year at Jazan University Medical School, Saudi Arabia. The course was held at the Research Center in Emergency and Disaster Medicine and Computer Sciences Applied to the Medical Practice in Novara, Italy. RESULTS: The overall mean score on a test given before the course was 41.0 % and it increased to 67.7 % on the post-test (Wilcoxon test for paired samples: z = 4.71, p < 0.0001). There were no significant differences between the mean scores of males and females, or between students in their fourth, fifth or sixth year of medical school. CONCLUSIONS: These results show that this curriculum is effective for teaching disaster medicine to undergraduate medical students. Adoption of this course would help to increase the human resources available for dealing with disaster situations.",2016 Aug 26,"['Bajow, Nidaa', 'Djalali, Ahmadreza', 'Ingrassia, Pier Luigi', 'Ragazzoni, Luca', 'Ageely, Hussein', 'Bani, Ibrahim', 'Corte, Francesco Della']",BMC Med Educ,,,True
c8f60c136e1ace8011a2ee3844510d862ff9053a,PMC,Risk of MERS importation and onward transmission: a systematic review and analysis of cases reported to WHO,http://dx.doi.org/10.1186/s12879-016-1787-5,PMC5000488,27562369,CC BY,"BACKGROUND: The continuing circulation of MERS in the Middle East makes the international dissemination of the disease a permanent threat. To inform risk assessment, we investigated the spatiotemporal pattern of MERS global dissemination and looked for factors explaining the heterogeneity observed in transmission events following importation. METHODS: We reviewed imported MERS cases worldwide up to July 2015. We modelled importations in time based on air travel combined with incidence in Middle East. We used the detailed history of MERS case management after importation (time to hospitalization and isolation, number of hospitals visited,…) in logistic regression to identify risk factors for secondary transmission. We assessed changes in time to hospitalization and isolation in relation to collective and public health attention to the epidemic, measured by three indicators (Google Trends, ProMED-mail, Disease Outbreak News). RESULTS: Modelled importation events were found to reproduce both the temporal and geographical structure of those observed – the Pearson correlation coefficient between predicted and observed monthly time series was large (r = 0.78, p < 10(−4)). The risk of secondary transmission following importation increased with the time to case isolation or death (OR = 1.7 p = 0.04) and more precisely with the duration of hospitalization (OR = 1.7, p = 0.02). The average daily number of secondary cases was 0.02 [0.0,0.12] in the community and 0.20 [0.03,9.0] in the hospital. Time from hospitalisation to isolation decreased in periods of high public health attention (2.33 ± 0.34 vs. 6.44 ± 0.97 days during baseline attention). CONCLUSIONS: Countries at risk of importation should focus their resources on strict infection control measures for the management of potential cases in healthcare settings and on prompt MERS cases identification. Individual and collective awareness are key to substantially improve such preparedness. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1787-5) contains supplementary material, which is available to authorized users.",2016 Aug 25,"['Poletto, Chiara', 'Boëlle, Pierre-Yves', 'Colizza, Vittoria']",BMC Infect Dis,,,True
3c20c596797997337c0e8ed472cf7847dc467c65,PMC,Risk of MERS importation and onward transmission: a systematic review and analysis of cases reported to WHO,http://dx.doi.org/10.1186/s12879-016-1787-5,PMC5000488,27562369,CC BY,"BACKGROUND: The continuing circulation of MERS in the Middle East makes the international dissemination of the disease a permanent threat. To inform risk assessment, we investigated the spatiotemporal pattern of MERS global dissemination and looked for factors explaining the heterogeneity observed in transmission events following importation. METHODS: We reviewed imported MERS cases worldwide up to July 2015. We modelled importations in time based on air travel combined with incidence in Middle East. We used the detailed history of MERS case management after importation (time to hospitalization and isolation, number of hospitals visited,…) in logistic regression to identify risk factors for secondary transmission. We assessed changes in time to hospitalization and isolation in relation to collective and public health attention to the epidemic, measured by three indicators (Google Trends, ProMED-mail, Disease Outbreak News). RESULTS: Modelled importation events were found to reproduce both the temporal and geographical structure of those observed – the Pearson correlation coefficient between predicted and observed monthly time series was large (r = 0.78, p < 10(−4)). The risk of secondary transmission following importation increased with the time to case isolation or death (OR = 1.7 p = 0.04) and more precisely with the duration of hospitalization (OR = 1.7, p = 0.02). The average daily number of secondary cases was 0.02 [0.0,0.12] in the community and 0.20 [0.03,9.0] in the hospital. Time from hospitalisation to isolation decreased in periods of high public health attention (2.33 ± 0.34 vs. 6.44 ± 0.97 days during baseline attention). CONCLUSIONS: Countries at risk of importation should focus their resources on strict infection control measures for the management of potential cases in healthcare settings and on prompt MERS cases identification. Individual and collective awareness are key to substantially improve such preparedness. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1787-5) contains supplementary material, which is available to authorized users.",2016 Aug 25,"['Poletto, Chiara', 'Boëlle, Pierre-Yves', 'Colizza, Vittoria']",BMC Infect Dis,,,True
b0691ba288acf449186c899b08788d6b4a2ecdeb,PMC,Biochemical and genetic analysis of the role of the viral polymerase in enterovirus recombination,http://dx.doi.org/10.1093/nar/gkw567,PMC5001610,27317698,CC BY,"Genetic recombination in single-strand, positive-sense RNA viruses is a poorly understand mechanism responsible for generating extensive genetic change and novel phenotypes. By moving a critical cis-acting replication element (CRE) from the polyprotein coding region to the 3′ non-coding region we have further developed a cell-based assay (the 3′CRE-REP assay) to yield recombinants throughout the non-structural coding region of poliovirus from dually transfected cells. We have additionally developed a defined biochemical assay in which the only protein present is the poliovirus RNA dependent RNA polymerase (RdRp), which recapitulates the strand transfer events of the recombination process. We have used both assays to investigate the role of the polymerase fidelity and nucleotide turnover rates in recombination. Our results, of both poliovirus intertypic and intratypic recombination in the CRE-REP assay and using a range of polymerase variants in the biochemical assay, demonstrate that RdRp fidelity is a fundamental determinant of recombination frequency. High fidelity polymerases exhibit reduced recombination and low fidelity polymerases exhibit increased recombination in both assays. These studies provide the basis for the analysis of poliovirus recombination throughout the non-structural region of the virus genome and provide a defined biochemical assay to further dissect this important evolutionary process.",2016 Aug 19,"['Woodman, Andrew', 'Arnold, Jamie\xa0J.', 'Cameron, Craig\xa0E.', 'Evans, David\xa0J.']",Nucleic Acids Res,,,True
5ebbe85f2c617784f1c7880858b0374263c87b57,PMC,Biochemical and genetic analysis of the role of the viral polymerase in enterovirus recombination,http://dx.doi.org/10.1093/nar/gkw567,PMC5001610,27317698,CC BY,"Genetic recombination in single-strand, positive-sense RNA viruses is a poorly understand mechanism responsible for generating extensive genetic change and novel phenotypes. By moving a critical cis-acting replication element (CRE) from the polyprotein coding region to the 3′ non-coding region we have further developed a cell-based assay (the 3′CRE-REP assay) to yield recombinants throughout the non-structural coding region of poliovirus from dually transfected cells. We have additionally developed a defined biochemical assay in which the only protein present is the poliovirus RNA dependent RNA polymerase (RdRp), which recapitulates the strand transfer events of the recombination process. We have used both assays to investigate the role of the polymerase fidelity and nucleotide turnover rates in recombination. Our results, of both poliovirus intertypic and intratypic recombination in the CRE-REP assay and using a range of polymerase variants in the biochemical assay, demonstrate that RdRp fidelity is a fundamental determinant of recombination frequency. High fidelity polymerases exhibit reduced recombination and low fidelity polymerases exhibit increased recombination in both assays. These studies provide the basis for the analysis of poliovirus recombination throughout the non-structural region of the virus genome and provide a defined biochemical assay to further dissect this important evolutionary process.",2016 Aug 19,"['Woodman, Andrew', 'Arnold, Jamie\xa0J.', 'Cameron, Craig\xa0E.', 'Evans, David\xa0J.']",Nucleic Acids Res,,,False
630a94063d188ceeb2302472ac2e1a0da2e31216,PMC,Consecutive Inhibition of ISG15 Expression and ISGylation by Cytomegalovirus Regulators,http://dx.doi.org/10.1371/journal.ppat.1005850,PMC5001722,27564865,CC BY,"Interferon-stimulated gene 15 (ISG15) encodes an ubiquitin-like protein that covalently conjugates protein. Protein modification by ISG15 (ISGylation) is known to inhibit the replication of many viruses. However, studies on the viral targets and viral strategies to regulate ISGylation-mediated antiviral responses are limited. In this study, we show that human cytomegalovirus (HCMV) replication is inhibited by ISGylation, but the virus has evolved multiple countermeasures. HCMV-induced ISG15 expression was mitigated by IE1, a viral inhibitor of interferon signaling, however, ISGylation was still strongly upregulated during virus infection. RNA interference of UBE1L (E1), UbcH8 (E2), Herc5 (E3), and UBP43 (ISG15 protease) revealed that ISGylation inhibits HCMV growth by downregulating viral gene expression and virion release in a manner that is more prominent at low multiplicity of infection. A viral regulator pUL26 was found to interact with ISG15, UBE1L, and Herc5, and be ISGylated. ISGylation of pUL26 regulated its stability and inhibited its activities to suppress NF-κB signaling and complement the growth of UL26-null mutant virus. Moreover, pUL26 reciprocally suppressed virus-induced ISGylation independent of its own ISGylation. Consistently, ISGylation was more pronounced in infections with the UL26-deleted mutant virus, whose growth was more sensitive to IFNβ treatment than that of the wild-type virus. Therefore, pUL26 is a viral ISG15 target that also counteracts ISGylation. Our results demonstrate that ISGylation inhibits HCMV growth at multiple steps and that HCMV has evolved countermeasures to suppress ISG15 transcription and protein ISGylation, highlighting the importance of the interplay between virus and ISGylation in productive viral infection.",2016 Aug 26,"['Kim, Ye Ji', 'Kim, Eui Tae', 'Kim, Young-Eui', 'Lee, Myoung Kyu', 'Kwon, Ki Mun', 'Kim, Keun Il', 'Stamminger, Thomas', 'Ahn, Jin-Hyun']",PLoS Pathog,,,True
421ee1f936a1714743c3cf06be01220009624a03,PMC,Analysis of Spatiotemporal Characteristics of Pandemic SARS Spread in Mainland China,http://dx.doi.org/10.1155/2016/7247983,PMC5002496,27597972,CC BY,"Severe acute respiratory syndrome (SARS) is one of the most severe emerging infectious diseases of the 21st century so far. SARS caused a pandemic that spread throughout mainland China for 7 months, infecting 5318 persons in 194 administrative regions. Using detailed mainland China epidemiological data, we study spatiotemporal aspects of this person-to-person contagious disease and simulate its spatiotemporal transmission dynamics via the Bayesian Maximum Entropy (BME) method. The BME reveals that SARS outbreaks show autocorrelation within certain spatial and temporal distances. We use BME to fit a theoretical covariance model that has a sine hole spatial component and exponential temporal component and obtain the weights of geographical and temporal autocorrelation factors. Using the covariance model, SARS dynamics were estimated and simulated under the most probable conditions. Our study suggests that SARS transmission varies in its epidemiological characteristics and SARS outbreak distributions exhibit palpable clusters on both spatial and temporal scales. In addition, the BME modelling demonstrates that SARS transmission features are affected by spatial heterogeneity, so we analyze potential causes. This may benefit epidemiological control of pandemic infectious diseases.",2016 Aug 15,"['Cao, Chunxiang', 'Chen, Wei', 'Zheng, Sheng', 'Zhao, Jian', 'Wang, Jinfeng', 'Cao, Wuchun']",Biomed Res Int,,,True
ebf25663cfe4314966c86a48ba4ce6a04a435760,PMC,Diminazene Aceturate Improves Cardiac Fibrosis and Diastolic Dysfunction in Rats with Kidney Disease,http://dx.doi.org/10.1371/journal.pone.0161760,PMC5003360,27571511,CC BY,"Angiotensin converting enzyme (ACE) 2 is a negative regulator of the renin angiotensin system (RAS) through its role to degrade angiotensin II. In rats with subtotal nephrectomy (STNx), adverse cardiac remodelling occurs despite elevated cardiac ACE2 activity. We hypothesised that diminazene aceturate (DIZE), which has been described as having an off-target effect to activate ACE2, would have beneficial cardiac effects in STNx rats. STNx led to hypertension, diastolic dysfunction, left ventricular hypertrophy, cardiac fibrosis, and increased cardiac ACE, ACE2, Ang II and Ang 1–7 levels. Cardiac gene expression of ADAM17 was also increased. In STNx, two-weeks of subcutaneous DIZE (15mg/kg/d) had no effect on blood pressure but improved diastolic dysfunction and cardiac fibrosis, reduced ADAM17 mRNA and shifted the cardiac RAS balance to a cardioprotective profile with reduced ACE and Ang II. There was no change in cardiac ACE2 activity or in cardiac Ang 1–7 levels with DIZE. In conclusion, our results suggest that DIZE exerts a protective effect on the heart under the pathological condition of kidney injury. This effect was not due to improved kidney function, a fall in blood pressure or a reduction in LVH but was associated with a reduction in cardiac ACE and cardiac Ang II levels. As in vitro studies showed no direct effect of DIZE on ACE2 or ACE activity, the precise mechanism of action of DIZE remains to be determined.",2016 Aug 29,"['Velkoska, Elena', 'Patel, Sheila K.', 'Griggs, Karen', 'Burrell, Louise M.']",PLoS One,,,True
3e72fd7554ad263eefddd4a0c6ee06afea606a44,PMC,Microarray for Identification of the Chiropteran Host Species of Rabies Virus in Canada,http://dx.doi.org/10.3390/microarrays2020153,PMC5003475,27605186,CC BY,"Species identification through genetic barcoding can augment traditional taxonomic methods, which rely on morphological features of the specimen. Such approaches are especially valuable when specimens are in poor condition or comprise very limited material, a situation that often applies to chiropteran (bat) specimens submitted to the Canadian Food Inspection Agency for rabies diagnosis. Coupled with phenotypic plasticity of many species and inconclusive taxonomic keys, species identification using only morphological traits can be challenging. In this study, a microarray assay with associated PCR of the mitochondrial cytochrome c oxidase subunit I (COI) gene was developed for differentiation of 14 bat species submitted to the Canadian Food Inspection Agency from 1985–2012 for rabies diagnosis. The assay was validated with a reference collection of DNA from 153 field samples, all of which had been barcoded previously. The COI gene from 152 samples which included multiple specimens of each target species were successfully amplified by PCR and accurately identified by the microarray. One sample that was severely decomposed failed to amplify with PCR primers developed in this study, but amplified weakly after switching to alternate primers and was accurately typed by the microarray. Thus, the chiropteran microarray was able to accurately differentiate between the 14 species of Canadian bats targeted. This PCR and microarray assay would allow unequivocal identification to species of most, if not all, bat specimens submitted for rabies diagnosis in Canada.",2013 May 31,"['Lung, Oliver', 'Nadin-Davis, Susan', 'Fisher, Mathew', 'Erickson, Anthony', 'Knowles, M. Kimberly', 'Furukawa-Stoffer, Tara', 'Ambagala, Aruna']",Microarrays (Basel),,,True
9287f4bf129f205faa654f47a2fb9a8af8a9526a,PMC,Subcellular redistribution and sequential recruitment of macromolecular components during SGIV assembly,http://dx.doi.org/10.1007/s13238-016-0292-3,PMC5003786,27430948,CC BY,"Virus infection consists of entry, synthesis of macromolecular components, virus assembly and release. Understanding of the mechanisms underlying each event is necessary for the intervention of virus infection in human healthcare and agriculture. Here we report the visualization of Singapore grouper iridovirus (SGIV) assembly in the medaka haploid embryonic stem (ES) cell line HX1. SGIV is a highly infectious DNA virus that causes a massive loss in marine aquaculture. Ectopic expression of VP88GFP, a fusion between green fluorescent protein and the envelope protein VP088, did not compromise the ES cell properties and susceptibility to SGIV infection. Although VP88GFP disperses evenly in the cytoplasm of non-infected cells, it undergoes aggregation and redistribution in SGIV-infected cells. Real-time visualization revealed multiple key stages of VP88GFP redistribution and the dynamics of viral assembly site (VAS). Specifically, VP88GFP entry into and condensation in the VAS occurred within a 6-h duration, a similar duration was observed also for the release of VP88GFP-containing SGIV out of the cell. Taken together, VP088 is an excellent marker for visualizing the SGIV infection process. Our results provide new insight into macromolecular component recruitment and SGIV assembly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-016-0292-3) contains supplementary material, which is available to authorized users.",2016 Sep 18,"['Yuan, Yongming', 'Hong, Yunhan']",Protein Cell,,,False
43fcca53a2dc667a4f8898dc2880d461bcbfbcff,PMC,Subcellular redistribution and sequential recruitment of macromolecular components during SGIV assembly,http://dx.doi.org/10.1007/s13238-016-0292-3,PMC5003786,27430948,CC BY,"Virus infection consists of entry, synthesis of macromolecular components, virus assembly and release. Understanding of the mechanisms underlying each event is necessary for the intervention of virus infection in human healthcare and agriculture. Here we report the visualization of Singapore grouper iridovirus (SGIV) assembly in the medaka haploid embryonic stem (ES) cell line HX1. SGIV is a highly infectious DNA virus that causes a massive loss in marine aquaculture. Ectopic expression of VP88GFP, a fusion between green fluorescent protein and the envelope protein VP088, did not compromise the ES cell properties and susceptibility to SGIV infection. Although VP88GFP disperses evenly in the cytoplasm of non-infected cells, it undergoes aggregation and redistribution in SGIV-infected cells. Real-time visualization revealed multiple key stages of VP88GFP redistribution and the dynamics of viral assembly site (VAS). Specifically, VP88GFP entry into and condensation in the VAS occurred within a 6-h duration, a similar duration was observed also for the release of VP88GFP-containing SGIV out of the cell. Taken together, VP088 is an excellent marker for visualizing the SGIV infection process. Our results provide new insight into macromolecular component recruitment and SGIV assembly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-016-0292-3) contains supplementary material, which is available to authorized users.",2016 Sep 18,"['Yuan, Yongming', 'Hong, Yunhan']",Protein Cell,,,False
0529ed2074b15413b032e82de1fcce37efde51a2,PMC,Subcellular redistribution and sequential recruitment of macromolecular components during SGIV assembly,http://dx.doi.org/10.1007/s13238-016-0292-3,PMC5003786,27430948,CC BY,"Virus infection consists of entry, synthesis of macromolecular components, virus assembly and release. Understanding of the mechanisms underlying each event is necessary for the intervention of virus infection in human healthcare and agriculture. Here we report the visualization of Singapore grouper iridovirus (SGIV) assembly in the medaka haploid embryonic stem (ES) cell line HX1. SGIV is a highly infectious DNA virus that causes a massive loss in marine aquaculture. Ectopic expression of VP88GFP, a fusion between green fluorescent protein and the envelope protein VP088, did not compromise the ES cell properties and susceptibility to SGIV infection. Although VP88GFP disperses evenly in the cytoplasm of non-infected cells, it undergoes aggregation and redistribution in SGIV-infected cells. Real-time visualization revealed multiple key stages of VP88GFP redistribution and the dynamics of viral assembly site (VAS). Specifically, VP88GFP entry into and condensation in the VAS occurred within a 6-h duration, a similar duration was observed also for the release of VP88GFP-containing SGIV out of the cell. Taken together, VP088 is an excellent marker for visualizing the SGIV infection process. Our results provide new insight into macromolecular component recruitment and SGIV assembly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-016-0292-3) contains supplementary material, which is available to authorized users.",2016 Sep 18,"['Yuan, Yongming', 'Hong, Yunhan']",Protein Cell,,,True
7fa2f5a443163614e02fa7b7d7c89fa535dc7b23,PMC,Tick-borne encephalitis virus induces chemokine RANTES expression via activation of IRF-3 pathway,http://dx.doi.org/10.1186/s12974-016-0665-9,PMC5004318,27576490,CC BY,"BACKGROUND: Tick-borne encephalitis virus (TBEV) is one of the most important flaviviruses that targets the central nervous system (CNS) and causes encephalitides in humans. Although neuroinflammatory mechanisms may contribute to brain tissue destruction, the induction pathways and potential roles of specific chemokines in TBEV-mediated neurological disease are poorly understood. METHODS: BALB/c mice were intracerebrally injected with TBEV, followed by evaluation of chemokine and cytokine profiles using protein array analysis. The virus-infected mice were treated with the CC chemokine antagonist Met-RANTES or anti-RANTES mAb to determine the role of RANTES in affecting TBEV-induced neurological disease. The underlying signaling mechanisms were delineated using RANTES promoter luciferase reporter assay, siRNA-mediated knockdown, and pharmacological inhibitors in human brain-derived cell culture models. RESULTS: In a mouse model, pathological features including marked inflammatory cell infiltrates were observed in brain sections, which correlated with a robust up-regulation of RANTES within the brain but not in peripheral tissues and sera. Antagonizing RANTES within CNS extended the survival of mice and reduced accumulation of infiltrating cells in the brain after TBEV infection. Through in vitro studies, we show that virus infection up-regulated RANTES production at both mRNA and protein levels in human brain-derived cell lines and primary progenitor-derived astrocytes. Furthermore, IRF-3 pathway appeared to be essential for TBEV-induced RANTES production. Site mutation of an IRF-3-binding motif abrogated the RANTES promoter activity in virus-infected brain cells. Moreover, IRF-3 was activated upon TBEV infection as evidenced by phosphorylation of TBK1 and IRF-3, while blockade of IRF-3 activation drastically reduced virus-induced RANTES expression. CONCLUSIONS: Our findings together provide insights into the molecular mechanism underlying RANTES production induced by TBEV, highlighting its potential importance in the process of neuroinflammatory responses to TBEV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-016-0665-9) contains supplementary material, which is available to authorized users.",2016 Aug 30,"['Zhang, Xiaowei', 'Zheng, Zhenhua', 'Liu, Xijuan', 'Shu, Bo', 'Mao, Panyong', 'Bai, Bingke', 'Hu, Qinxue', 'Luo, Minhua', 'Ma, Xiaohe', 'Cui, Zongqiang', 'Wang, Hanzhong']",J Neuroinflammation,,,True
514a5ab6c1549c33d8acf502b929bc0699f5e21c,PMC,"Human Respiratory Coronaviruses Detected In Patients with Influenza-Like Illness in Arkansas, USA",http://dx.doi.org/10.4172/2161-0517.S2-004,PMC5004774,27588218,CC BY,"Acute respiratory viruses often result in significant morbidity and mortality. The potential impact of human respiratory coronavirus (CoV) infections was underestimated until the severe acute respiratory syndrome (SARS-CoV) outbreak in 2003, which showed that new, highly pathogenic coronaviruses could be introduced to humans, highlighting the importance of monitoring the circulating coronaviruses. The use of sensitive molecular methods has contributed to the differential diagnosis of viruses circulating in humans. Our study aim was to investigate the molecular epidemiology of human CoV strains circulating in Arkansas, their genetic variability and their association with reported influenza-like symptoms. We analyzed 200 nasal swab samples, collected by the Arkansas Department of Health in 2010, for influenza diagnosis. All samples were from patients showing acute respiratory symptoms while testing negative for influenza. Samples were pre-screened, using a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) multiprobe for coronavirus, and subjected to confirmatory pancoronavirus and/or strain-specific reverse transcriptase (RT)-PCR followed by sequence analysis. Seventy-nine samples (39.5%) were positive by qRT-PCR and 35 samples (17.5%) were confirmed by conventional RT-PCR. Twenty-three of the confirmed samples (59%) were sequenced. The most frequent strain detected was HCoV-OC43-like followed by NL63-like; only one sample was positive for HCoV-229E and one for HCoV-HKU1. Feline-like CoV strains were detected in three samples, representing possible evidence of interspecies transmission or a new human strain. Seventeen percent of the coronavirus positive samples were also positive for other respiratory viruses, such as Respiratory Syncytial Virus (RSV), Parainfluenza 2 and 3, and Rhinovirus. Thus, HCoV-OC43, NL63, HKU1 and new feline-like strains were circulating in Arkansas in 2010. HCoV was the sole respiratory virus detected in 16% of the patients who showed acute respiratory symptoms with negative diagnoses for influenza virus.",2014 Dec 26,"['Silva, Camila S', 'Mullis, Lisa B', 'Pereira, Olavo', 'Saif, Linda J', 'Vlasova, Anastasia', 'Zhang, Xuming', 'Owens, Randall J', 'Paulson, Dale', 'Taylor, Deborah', 'Haynes, Lia M', 'Azevedo, Marli P']",Virol Mycol,,,True
82bf46aebd99e6e67368b9c789d01e561ed147af,PMC,High-Throughput Sequencing-Based Immune Repertoire Study during Infectious Disease,http://dx.doi.org/10.3389/fimmu.2016.00336,PMC5005336,27630639,CC BY,"The selectivity of the adaptive immune response is based on the enormous diversity of T and B cell antigen-specific receptors. The immune repertoire, the collection of T and B cells with functional diversity in the circulatory system at any given time, is dynamic and reflects the essence of immune selectivity. In this article, we review the recent advances in immune repertoire study of infectious diseases, which were achieved by traditional techniques and high-throughput sequencing (HTS) techniques. HTS techniques enable the determination of complementary regions of lymphocyte receptors with unprecedented efficiency and scale. This progress in methodology enhances the understanding of immunologic changes during pathogen challenge and also provides a basis for further development of novel diagnostic markers, immunotherapies, and vaccines.",2016 Aug 31,"['Hou, Dongni', 'Chen, Cuicui', 'Seely, Eric John', 'Chen, Shujing', 'Song, Yuanlin']",Front Immunol,,,True
4ea1d124972eda4c488d6446f88964f60bed47fc,PMC,Changes in the Transcriptome of Human Astrocytes Accompanying Oxidative Stress-Induced Senescence,http://dx.doi.org/10.3389/fnagi.2016.00208,PMC5005348,27630559,CC BY,"Aging is a major risk factor for many neurodegenerative disorders. A key feature of aging biology that may underlie these diseases is cellular senescence. Senescent cells accumulate in tissues with age, undergo widespread changes in gene expression, and typically demonstrate altered, pro-inflammatory profiles. Astrocyte senescence has been implicated in neurodegenerative disease, and to better understand senescence-associated changes in astrocytes, we investigated changes in their transcriptome using RNA sequencing. Senescence was induced in human fetal astrocytes by transient oxidative stress. Brain-expressed genes, including those involved in neuronal development and differentiation, were downregulated in senescent astrocytes. Remarkably, several genes indicative of astrocytic responses to injury were also downregulated, including glial fibrillary acidic protein and genes involved in the processing and presentation of antigens by major histocompatibility complex class II proteins, while pro-inflammatory genes were upregulated. Overall, our findings suggest that senescence-related changes in the function of astrocytes may impact the pathogenesis of age-related brain disorders.",2016 Aug 31,"['Crowe, Elizabeth P.', 'Tuzer, Ferit', 'Gregory, Brian D.', 'Donahue, Greg', 'Gosai, Sager J.', 'Cohen, Justin', 'Leung, Yuk Y.', 'Yetkin, Emre', 'Nativio, Raffaella', 'Wang, Li-San', 'Sell, Christian', 'Bonini, Nancy M.', 'Berger, Shelley L.', 'Johnson, F. Brad', 'Torres, Claudio']",Front Aging Neurosci,,,True
53db274f4427f9f421959b5d0e6b5dc47c58612a,PMC,Type I IFN Signaling Is Dispensable during Secondary Viral Infection,http://dx.doi.org/10.1371/journal.ppat.1005861,PMC5006979,27580079,CC BY,"Innate immune responses in general, and type I interferons (T1IFNs) in particular, play an important and often essential role during primary viral infections, by directly combatting the virus and by maximizing the primary adaptive immune response. Several studies have suggested that T1IFNs also contribute very substantially to the secondary (recall) response; they are thought (i) to be required to drive the early attrition of memory T cells, (ii) to support the subsequent expansion of surviving virus-specific memory cells, and (iii) to assist in the suppression and clearance of the infectious agent. However, many of these observations were predicated upon models in which T1IFN signaling was interrupted prior to a primary immune response, raising the possibility that the resulting memory cells might be intrinsically abnormal. We have directly addressed this by using an inducible-Cre model system in which the host remains genetically-intact during the primary response to infection, and in which T1IFN signaling can be effectively ablated prior to secondary viral challenge. We report that, in stark contrast to primary infection, T1IFN signaling is not required during the recall response. IFNαβR-deficient memory CD8(+) and CD4(+) memory T cells undergo attrition and expansion with kinetics that are indistinguishable from those of receptor-sufficient cells. Moreover, even in the absence of functional T1IFN signaling, the host’s immune capacity to rapidly suppress, and then to eradicate, a secondary infection remains intact. Thus, this study shows that T1IFN signaling is dispensable during the recall response to a virus infection. Moreover, two broader implications may be drawn. First, a T cell’s requirement for a cytokine is highly dependent on the cell’s maturation / differentiation status. Consequently, second, these data underscore the importance of evaluating a gene’s impact by modulating its expression or function in a temporally-controllable manner.",2016 Aug 31,"['Hosking, Martin P.', 'Flynn, Claudia T.', 'Whitton, J. Lindsay']",PLoS Pathog,,,True
237cdea88e640a5848e7abb82992894618315d63,PMC,The Occupational Risk of Influenza A (H1N1) Infection among Healthcare Personnel during the 2009 Pandemic: A Systematic Review and Meta-Analysis of Observational Studies,http://dx.doi.org/10.1371/journal.pone.0162061,PMC5006982,27579923,CC BY,"INTRODUCTION: The aim of this review was to record systematically and assess the published literature relating to the occupational risk of influenza A (H1N1) infection among healthcare personnel during the 2009 pandemic. METHODS: The literature search was performed in June 2015. An update was carried out in May 2016. It was applied to the electronic databases EMBASE, MEDLINE, PsycINFO, PubMed, CINAHL and Google Scholar. The quality assessment was conducted with a tool using eight criteria. A meta-analysis was carried out to compute pooled effect estimates for influenza A (H1N1) infection. RESULTS: A total of 26 studies were included in the review, 15 studies met the criteria for the meta-analysis. After a sensitivity analysis the pooled analysis showed a significantly increased odds for influenza A (H1N1) infection for healthcare personnel compared to controls/comparisons (OR = 2.08, 95% CI = 1.73 to 2.51). The pooled prevalence rate for healthcare personnel alone was 6.3%. CONCLUSIONS: This review corroborates the assumption that healthcare personnel were particularly at risk of influenza A (H1N1) infection during the 2009 pandemic. Healthcare facilities should intensify their focus on strategies to prevent infections among healthcare personnel, especially during the first period of pandemics.",2016 Aug 31,"['Lietz, Janna', 'Westermann, Claudia', 'Nienhaus, Albert', 'Schablon, Anja']",PLoS One,,,True
e80998b803a0a3a554bf0a0f923f65df16d7a1df,PMC,The Occupational Risk of Influenza A (H1N1) Infection among Healthcare Personnel during the 2009 Pandemic: A Systematic Review and Meta-Analysis of Observational Studies,http://dx.doi.org/10.1371/journal.pone.0162061,PMC5006982,27579923,CC BY,"INTRODUCTION: The aim of this review was to record systematically and assess the published literature relating to the occupational risk of influenza A (H1N1) infection among healthcare personnel during the 2009 pandemic. METHODS: The literature search was performed in June 2015. An update was carried out in May 2016. It was applied to the electronic databases EMBASE, MEDLINE, PsycINFO, PubMed, CINAHL and Google Scholar. The quality assessment was conducted with a tool using eight criteria. A meta-analysis was carried out to compute pooled effect estimates for influenza A (H1N1) infection. RESULTS: A total of 26 studies were included in the review, 15 studies met the criteria for the meta-analysis. After a sensitivity analysis the pooled analysis showed a significantly increased odds for influenza A (H1N1) infection for healthcare personnel compared to controls/comparisons (OR = 2.08, 95% CI = 1.73 to 2.51). The pooled prevalence rate for healthcare personnel alone was 6.3%. CONCLUSIONS: This review corroborates the assumption that healthcare personnel were particularly at risk of influenza A (H1N1) infection during the 2009 pandemic. Healthcare facilities should intensify their focus on strategies to prevent infections among healthcare personnel, especially during the first period of pandemics.",2016 Aug 31,"['Lietz, Janna', 'Westermann, Claudia', 'Nienhaus, Albert', 'Schablon, Anja']",PLoS One,,,False
31cc00c5c0a5298a2e22068195971a9e5f3a4fe4,PMC,The Occupational Risk of Influenza A (H1N1) Infection among Healthcare Personnel during the 2009 Pandemic: A Systematic Review and Meta-Analysis of Observational Studies,http://dx.doi.org/10.1371/journal.pone.0162061,PMC5006982,27579923,CC BY,"INTRODUCTION: The aim of this review was to record systematically and assess the published literature relating to the occupational risk of influenza A (H1N1) infection among healthcare personnel during the 2009 pandemic. METHODS: The literature search was performed in June 2015. An update was carried out in May 2016. It was applied to the electronic databases EMBASE, MEDLINE, PsycINFO, PubMed, CINAHL and Google Scholar. The quality assessment was conducted with a tool using eight criteria. A meta-analysis was carried out to compute pooled effect estimates for influenza A (H1N1) infection. RESULTS: A total of 26 studies were included in the review, 15 studies met the criteria for the meta-analysis. After a sensitivity analysis the pooled analysis showed a significantly increased odds for influenza A (H1N1) infection for healthcare personnel compared to controls/comparisons (OR = 2.08, 95% CI = 1.73 to 2.51). The pooled prevalence rate for healthcare personnel alone was 6.3%. CONCLUSIONS: This review corroborates the assumption that healthcare personnel were particularly at risk of influenza A (H1N1) infection during the 2009 pandemic. Healthcare facilities should intensify their focus on strategies to prevent infections among healthcare personnel, especially during the first period of pandemics.",2016 Aug 31,"['Lietz, Janna', 'Westermann, Claudia', 'Nienhaus, Albert', 'Schablon, Anja']",PLoS One,,,True
94f96f58a3d4328d9e1af3aba7ed1b8660689191,PMC,The Occupational Risk of Influenza A (H1N1) Infection among Healthcare Personnel during the 2009 Pandemic: A Systematic Review and Meta-Analysis of Observational Studies,http://dx.doi.org/10.1371/journal.pone.0162061,PMC5006982,27579923,CC BY,"INTRODUCTION: The aim of this review was to record systematically and assess the published literature relating to the occupational risk of influenza A (H1N1) infection among healthcare personnel during the 2009 pandemic. METHODS: The literature search was performed in June 2015. An update was carried out in May 2016. It was applied to the electronic databases EMBASE, MEDLINE, PsycINFO, PubMed, CINAHL and Google Scholar. The quality assessment was conducted with a tool using eight criteria. A meta-analysis was carried out to compute pooled effect estimates for influenza A (H1N1) infection. RESULTS: A total of 26 studies were included in the review, 15 studies met the criteria for the meta-analysis. After a sensitivity analysis the pooled analysis showed a significantly increased odds for influenza A (H1N1) infection for healthcare personnel compared to controls/comparisons (OR = 2.08, 95% CI = 1.73 to 2.51). The pooled prevalence rate for healthcare personnel alone was 6.3%. CONCLUSIONS: This review corroborates the assumption that healthcare personnel were particularly at risk of influenza A (H1N1) infection during the 2009 pandemic. Healthcare facilities should intensify their focus on strategies to prevent infections among healthcare personnel, especially during the first period of pandemics.",2016 Aug 31,"['Lietz, Janna', 'Westermann, Claudia', 'Nienhaus, Albert', 'Schablon, Anja']",PLoS One,,,False
266e97136335f2ef19dd7d372fe0472afa2af17c,PMC,Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses,http://dx.doi.org/10.1371/journal.ppat.1005817,PMC5007037,27579713,CC BY,"Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine-induced antibodies and therapeutic antibodies will enable a better understanding of their capacity to prevent and/or control HIV-1 infection in vivo.",2016 Aug 31,"['Tay, Matthew Zirui', 'Liu, Pinghuang', 'Williams, LaTonya D.', 'McRaven, Michael D', 'Sawant, Sheetal', 'Gurley, Thaddeus C', 'Xu, Thomas T.', 'Dennison, S. Moses', 'Liao, Hua-Xin', 'Chenine, Agnès-Laurence', 'Alam, S. Munir', 'Moody, M. Anthony', 'Hope, Thomas J.', 'Haynes, Barton F.', 'Tomaras, Georgia D.']",PLoS Pathog,,,True
67139d212b2529bb07805e78304619d373dd35d9,PMC,"Economic burden and its associated factors of hospitalized patients infected with A (H7N9) virus: a retrospective study in Eastern China, 2013–2014",http://dx.doi.org/10.1186/s40249-016-0170-5,PMC5007809,27580946,CC BY,"BACKGROUND: H7N9 continues to cause human infections and remains a pandemic concern. Understanding the economic impacts of this novel disease is important for making decisions on health resource allocation, including infectious disease prevention and control investment. However, there are limited data on such impacts. METHODS: Hospitalized laboratory-confirmed H7N9 patients or their families in Jiangsu Province of China were interviewed. Patients’ direct medical costs of hospitalization were derived from their hospital bills. A generalized linear model was employed to estimate the mean direct medical costs of patients with different characteristics. RESULTS: The mean direct cost of hospitalization for H7N9 was estimated to be ¥ 71 060 (95 % CI, 48 180–104 820), i.e., US$ 10 996 (95 % CI, 7 455–16 220), and was ¥12 060 (US$ 1 861), ¥136 120 (US$ 21 001) and ¥218 610 (US$ 33 728) for those who had mild or severe symptoms or who died, respectively. The principal components of the total fees differed among patients with different disease severity, although medication fees were always the largest contributors. Disease severity, proportion of reimbursement and family member monthly average income were identified as the key factors that contributed to a patient’s direct medical cost of hospitalization. CONCLUSIONS: The direct medical costs of hospitalized patients with H7N9 are significant, and far surpass the annual per capita income of Jiangsu Province, China. The influencing factors identified should be taken into account when developing related health insurance policies and making health resource allocation. TRIAL REGISTRATION: Not applicable. This is a survey study with no health care intervention implemented on human participants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0170-5) contains supplementary material, which is available to authorized users.",2016 Sep 1,"['Huo, Xiang', 'Chen, Li-Ling', 'Hong, Lei', 'Xiang, Lun-Hui', 'Tang, Fen-Yang', 'Chen, Shan-Hui', 'Gao, Qiang', 'Chen, Cong', 'Dai, Qi-gang', 'Sun, Chuan-Wu', 'Xu, Ke', 'Dai, Wen-Jun', 'Qi, Xian', 'Li, Chang-Cheng', 'Yu, Hui-Yan', 'Zhou, Yin', 'Huang, Hao-Di', 'Pan, Xing-Yang', 'Xu, Chang-sha', 'Zhou, Ming-Hao', 'Bao, Chang-Jun']",Infect Dis Poverty,,,False
bb6e40ae1720fa7008aa90c2c35d9d7e75c4611e,PMC,"Economic burden and its associated factors of hospitalized patients infected with A (H7N9) virus: a retrospective study in Eastern China, 2013–2014",http://dx.doi.org/10.1186/s40249-016-0170-5,PMC5007809,27580946,CC BY,"BACKGROUND: H7N9 continues to cause human infections and remains a pandemic concern. Understanding the economic impacts of this novel disease is important for making decisions on health resource allocation, including infectious disease prevention and control investment. However, there are limited data on such impacts. METHODS: Hospitalized laboratory-confirmed H7N9 patients or their families in Jiangsu Province of China were interviewed. Patients’ direct medical costs of hospitalization were derived from their hospital bills. A generalized linear model was employed to estimate the mean direct medical costs of patients with different characteristics. RESULTS: The mean direct cost of hospitalization for H7N9 was estimated to be ¥ 71 060 (95 % CI, 48 180–104 820), i.e., US$ 10 996 (95 % CI, 7 455–16 220), and was ¥12 060 (US$ 1 861), ¥136 120 (US$ 21 001) and ¥218 610 (US$ 33 728) for those who had mild or severe symptoms or who died, respectively. The principal components of the total fees differed among patients with different disease severity, although medication fees were always the largest contributors. Disease severity, proportion of reimbursement and family member monthly average income were identified as the key factors that contributed to a patient’s direct medical cost of hospitalization. CONCLUSIONS: The direct medical costs of hospitalized patients with H7N9 are significant, and far surpass the annual per capita income of Jiangsu Province, China. The influencing factors identified should be taken into account when developing related health insurance policies and making health resource allocation. TRIAL REGISTRATION: Not applicable. This is a survey study with no health care intervention implemented on human participants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0170-5) contains supplementary material, which is available to authorized users.",2016 Sep 1,"['Huo, Xiang', 'Chen, Li-Ling', 'Hong, Lei', 'Xiang, Lun-Hui', 'Tang, Fen-Yang', 'Chen, Shan-Hui', 'Gao, Qiang', 'Chen, Cong', 'Dai, Qi-gang', 'Sun, Chuan-Wu', 'Xu, Ke', 'Dai, Wen-Jun', 'Qi, Xian', 'Li, Chang-Cheng', 'Yu, Hui-Yan', 'Zhou, Yin', 'Huang, Hao-Di', 'Pan, Xing-Yang', 'Xu, Chang-sha', 'Zhou, Ming-Hao', 'Bao, Chang-Jun']",Infect Dis Poverty,,,True
cbc96926929c9fd4fe5e83928688041b3bdde491,PMC,Viral Manipulation of Host Inhibitory Receptor Signaling for Immune Evasion,http://dx.doi.org/10.1371/journal.ppat.1005776,PMC5008827,27584579,CC BY,,2016 Sep 1,"['Ong, Eugenia Z.', 'Chan, Kuan Rong', 'Ooi, Eng Eong']",PLoS Pathog,,,True
0cec675c685c32258b42e915ab84a45851b6dd26,PMC,Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use,http://dx.doi.org/10.1093/nar/gkw530,PMC5009743,27436286,CC BY,"Genetic decoding is not ‘frozen’ as was earlier thought, but dynamic. One facet of this is frameshifting that often results in synthesis of a C-terminal region encoded by a new frame. Ribosomal frameshifting is utilized for the synthesis of additional products, for regulatory purposes and for translational ‘correction’ of problem or ‘savior’ indels. Utilization for synthesis of additional products occurs prominently in the decoding of mobile chromosomal element and viral genomes. One class of regulatory frameshifting of stable chromosomal genes governs cellular polyamine levels from yeasts to humans. In many cases of productively utilized frameshifting, the proportion of ribosomes that frameshift at a shift-prone site is enhanced by specific nascent peptide or mRNA context features. Such mRNA signals, which can be 5′ or 3′ of the shift site or both, can act by pairing with ribosomal RNA or as stem loops or pseudoknots even with one component being 4 kb 3′ from the shift site. Transcriptional realignment at slippage-prone sequences also generates productively utilized products encoded trans-frame with respect to the genomic sequence. This too can be enhanced by nucleic acid structure. Together with dynamic codon redefinition, frameshifting is one of the forms of recoding that enriches gene expression.",2016 Sep 6,"['Atkins, John F.', 'Loughran, Gary', 'Bhatt, Pramod R.', 'Firth, Andrew E.', 'Baranov, Pavel V.']",Nucleic Acids Res,,,True
0cf083b09e13b9c6d8fe008590784d479f67f2f6,PMC,Low genetic diversity among historical and contemporary clinical isolates of felid herpesvirus 1,http://dx.doi.org/10.1186/s12864-016-3050-2,PMC5010698,27589862,CC BY,"BACKGROUND: Felid herpesvirus 1 (FHV-1) causes upper respiratory tract diseases in cats worldwide, including nasal and ocular discharge, conjunctivitis and oral ulceration. The nature and severity of disease can vary between clinical cases. Genetic determinants of virulence are likely to contribute to differences in the in vivo phenotype of FHV-1 isolates, but to date there have been limited studies investigating FHV-1 genetic diversity. This study used next generation sequencing to compare the genomes of contemporary Australian clinical isolates of FHV-1, vaccine isolates and historical clinical isolates, including isolates that predated the introduction of live attenuated vaccines into Australia. Analysis of the genome sequences aimed to assess the level of genetic diversity, identify potential genetic markers that could influence the in vivo phenotype of the isolates and examine the sequences for evidence of recombination. RESULTS: The full genome sequences of 26 isolates of FHV-1 were determined, including two vaccine isolates and 24 clinical isolates that were collected over a period of approximately 40 years. Analysis of the genome sequences revealed a remarkably low level of diversity (0.0–0.01 %) between the isolates. No potential genetic determinants of virulence were identified, but unique single nucleotide polymorphisms (SNPs) in the UL28 and UL44 genes were detected in the vaccine isolates that were not present in the clinical isolates. No evidence of FHV-1 recombination was detected using multiple methods of recombination detection, even though many of the isolates originated from cats housed in a shelter environment where high infective pressures were likely to exist. Evidence of displacement of dominant FHV-1 isolates with other (genetically distinct) FHV-1 isolates over time was observed amongst the isolates obtained from the shelter-housed animals. CONCLUSIONS: The results show that FHV-1 genomes are highly conserved. The lack of recombination detected in the FHV-1 genomes suggests that the risk of attenuated vaccines recombining to generate virulent field viruses is lower than has been suggested for some other herpesviruses. The SNPs detected only in the vaccine isolates offer the potential to develop PCR-based methods of differentiating vaccine and clinical isolates of FHV-1 in order to facilitate future epidemiological studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3050-2) contains supplementary material, which is available to authorized users.",2016 Sep 2,"['Vaz, Paola K.', 'Job, Natalie', 'Horsington, Jacquelyn', 'Ficorilli, Nino', 'Studdert, Michael J.', 'Hartley, Carol A.', 'Gilkerson, James R.', 'Browning, Glenn F.', 'Devlin, Joanne M.']",BMC Genomics,,,True
647652b31779d67fcdecf1848f7492b2ab10a4ee,PMC,High correlation of Middle East respiratory syndrome spread with Google search and Twitter trends in Korea,http://dx.doi.org/10.1038/srep32920,PMC5011762,27595921,CC BY,"The Middle East respiratory syndrome coronavirus (MERS-CoV) was exported to Korea in 2015, resulting in a threat to neighboring nations. We evaluated the possibility of using a digital surveillance system based on web searches and social media data to monitor this MERS outbreak. We collected the number of daily laboratory-confirmed MERS cases and quarantined cases from May 11, 2015 to June 26, 2015 using the Korean government MERS portal. The daily trends observed via Google search and Twitter during the same time period were also ascertained using Google Trends and Topsy. Correlations among the data were then examined using Spearman correlation analysis. We found high correlations (>0.7) between Google search and Twitter results and the number of confirmed MERS cases for the previous three days using only four simple keywords: “MERS”, “[Image: see text]” (“MERS (in Korean)”), “[Image: see text]” (“MERS symptoms (in Korean)”), and “[Image: see text]” (“MERS hospital (in Korean)”). Additionally, we found high correlations between the Google search and Twitter results and the number of quarantined cases using the above keywords. This study demonstrates the possibility of using a digital surveillance system to monitor the outbreak of MERS.",2016 Sep 6,"['Shin, Soo-Yong', 'Seo, Dong-Woo', 'An, Jisun', 'Kwak, Haewoon', 'Kim, Sung-Han', 'Gwack, Jin', 'Jo, Min-Woo']",Sci Rep,,,True
3f01163d7045653eac4e5ba5186c3444a358a594,PMC,High correlation of Middle East respiratory syndrome spread with Google search and Twitter trends in Korea,http://dx.doi.org/10.1038/srep32920,PMC5011762,27595921,CC BY,"The Middle East respiratory syndrome coronavirus (MERS-CoV) was exported to Korea in 2015, resulting in a threat to neighboring nations. We evaluated the possibility of using a digital surveillance system based on web searches and social media data to monitor this MERS outbreak. We collected the number of daily laboratory-confirmed MERS cases and quarantined cases from May 11, 2015 to June 26, 2015 using the Korean government MERS portal. The daily trends observed via Google search and Twitter during the same time period were also ascertained using Google Trends and Topsy. Correlations among the data were then examined using Spearman correlation analysis. We found high correlations (>0.7) between Google search and Twitter results and the number of confirmed MERS cases for the previous three days using only four simple keywords: “MERS”, “[Image: see text]” (“MERS (in Korean)”), “[Image: see text]” (“MERS symptoms (in Korean)”), and “[Image: see text]” (“MERS hospital (in Korean)”). Additionally, we found high correlations between the Google search and Twitter results and the number of quarantined cases using the above keywords. This study demonstrates the possibility of using a digital surveillance system to monitor the outbreak of MERS.",2016 Sep 6,"['Shin, Soo-Yong', 'Seo, Dong-Woo', 'An, Jisun', 'Kwak, Haewoon', 'Kim, Sung-Han', 'Gwack, Jin', 'Jo, Min-Woo']",Sci Rep,,,False
d0f0d83e31f3b077e623fc38a388fed8e8c1db3e,PMC,"Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler",http://dx.doi.org/10.1186/s12864-016-3030-6,PMC5011931,27595578,CC BY,"BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.",2016 Sep 5,"['Shepard, Samuel S.', 'Meno, Sarah', 'Bahl, Justin', 'Wilson, Malania M.', 'Barnes, John', 'Neuhaus, Elizabeth']",BMC Genomics,,,False
581f3f4246eb93bf7602fe189214bdcb1596cbfd,PMC,"Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler",http://dx.doi.org/10.1186/s12864-016-3030-6,PMC5011931,27595578,CC BY,"BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.",2016 Sep 5,"['Shepard, Samuel S.', 'Meno, Sarah', 'Bahl, Justin', 'Wilson, Malania M.', 'Barnes, John', 'Neuhaus, Elizabeth']",BMC Genomics,,,False
b00cbcd12b11a836fa85bf2c720e36fda7c91a1d,PMC,"Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler",http://dx.doi.org/10.1186/s12864-016-3030-6,PMC5011931,27595578,CC BY,"BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.",2016 Sep 5,"['Shepard, Samuel S.', 'Meno, Sarah', 'Bahl, Justin', 'Wilson, Malania M.', 'Barnes, John', 'Neuhaus, Elizabeth']",BMC Genomics,,,False
e436cf6b2d5bd9b2d9146b34f22301b0e4eb3747,PMC,"Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler",http://dx.doi.org/10.1186/s12864-016-3030-6,PMC5011931,27595578,CC BY,"BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.",2016 Sep 5,"['Shepard, Samuel S.', 'Meno, Sarah', 'Bahl, Justin', 'Wilson, Malania M.', 'Barnes, John', 'Neuhaus, Elizabeth']",BMC Genomics,,,False
15a1fc721871b0814cd07102842bbb982159a083,PMC,"Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler",http://dx.doi.org/10.1186/s12864-016-3030-6,PMC5011931,27595578,CC BY,"BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.",2016 Sep 5,"['Shepard, Samuel S.', 'Meno, Sarah', 'Bahl, Justin', 'Wilson, Malania M.', 'Barnes, John', 'Neuhaus, Elizabeth']",BMC Genomics,,,False
5da2a49bdb5d4cef0e9e918bcbf85d3f97dabd99,PMC,"Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler",http://dx.doi.org/10.1186/s12864-016-3030-6,PMC5011931,27595578,CC BY,"BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.",2016 Sep 5,"['Shepard, Samuel S.', 'Meno, Sarah', 'Bahl, Justin', 'Wilson, Malania M.', 'Barnes, John', 'Neuhaus, Elizabeth']",BMC Genomics,,,False
3de7d38c011f33930835b63043d70fb107a26700,PMC,"Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler",http://dx.doi.org/10.1186/s12864-016-3030-6,PMC5011931,27595578,CC BY,"BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.",2016 Sep 5,"['Shepard, Samuel S.', 'Meno, Sarah', 'Bahl, Justin', 'Wilson, Malania M.', 'Barnes, John', 'Neuhaus, Elizabeth']",BMC Genomics,,,False
940de307debf3a9042f73ef7cd17fa7a2464d408,PMC,"Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler",http://dx.doi.org/10.1186/s12864-016-3030-6,PMC5011931,27595578,CC BY,"BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.",2016 Sep 5,"['Shepard, Samuel S.', 'Meno, Sarah', 'Bahl, Justin', 'Wilson, Malania M.', 'Barnes, John', 'Neuhaus, Elizabeth']",BMC Genomics,,,True
04c221e49d8355ce52360d5e37dc583f6502cc92,PMC,"In vitro antimicrobial activities of animal-used quinoxaline 1,4-di-N-oxides against mycobacteria, mycoplasma and fungi",http://dx.doi.org/10.1186/s12917-016-0812-7,PMC5011961,27600955,CC BY,"BACKGROUND: The quinoxaline 1,4-di-N-oxides (QdNOs) were known as potent antibacterial agents. For the purpose of evaluating the bioactivity of existing animal-used QdNOs drugs against representative pathogenic microorganism, the representative drugs of quinoxalines including cyadox, mequindox, quinocetone and their metabolites were submitted to the in vitro evaluation for antituberculosis, antimycoplasma, antifungal and antiviral activities. RESULTS: In antituberculosis assays, the prototype compounds were active (MIC = 4 ~ 8 μg/mL) against Mycobacterium tuberculosis H37Rv and M. bovis. Combined antimicrobial susceptibility test indicated that cyadox, mequindox and quinocetone combined with rifampicin had additive effect against M. tuberculosis complex with Fractional Inhibitory Concentration Index (FIC) of 0.75. Results of antifungal assays showed that quinocetone was active against Microsporum canis with MIC of 8 μg/mL. Antimycoplasma screening showed a generally good activity of quinocetone against Mycoplasma gallisepticum and Mycoplasma hyopneumoniae, with MIC between 8 and 16 μg/mL. As shown from the combined antimicrobial susceptibility test, cyadox, mequindox and quinocetone combined with tetracycline had additive effect against Mycoplasma gallisepticum with FIC of 0.75. These compounds were also submitted to antiviral assay against infectious bursal disease virus, porcine reproductive and respiratory syndrome virus, porcine parvovirus and classical swine fever virus. The results obtained showed that these QdNOs and their metabolites have no inhibitory activity against these viruses in vitro. CONCLUSIONS: QdNOs exhibit antimicrobial activities against mycobacteria, mycoplasma and fungi. This study gives new insight in further application of QdNOs and offers a way to promote the healthcare of animal husbandry. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0812-7) contains supplementary material, which is available to authorized users.",2016 Sep 6,"['Zhao, Yan', 'Cheng, Guyue', 'Hao, Haihong', 'Pan, Yuanhu', 'Liu, Zhenli', 'Dai, Menghong', 'Yuan, Zonghui']",BMC Vet Res,,,True
693a04c2c05485c6f19c6fc281ebf65dc4fe06dc,PMC,Molecular Biology and Infection of Hepatitis E Virus,http://dx.doi.org/10.3389/fmicb.2016.01419,PMC5013053,27656178,CC BY,"Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus.",2016 Sep 7,"['Nan, Yuchen', 'Zhang, Yan-Jin']",Front Microbiol,,,True
cc4ee2499ad533a2201243233dfbd178aa3b7185,PMC,CEACAM1: Expression and Role in Melanocyte Transformation,http://dx.doi.org/10.1155/2016/9406319,PMC5013198,27642217,CC BY,"Metastases represent the main cause of death in melanoma patients. Despite the current optimized targeted therapy or immune checkpoint inhibitors the treatment of metastatic melanoma is unsatisfactory. Because of the poor prognosis of advanced melanoma there is an urgent need to identify new biomarkers to differentiate melanoma cells from normal melanocytes, to stratify patients according to their risk, and to identify subgroups of patients that require close follow-up or more aggressive therapy. Furthermore, melanoma progression has been associated with the dysregulation of cell adhesion molecules. We have reviewed the literature and have discussed the important role of the expression of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in the development of melanoma. Thus, novel insights into CEACAM1 may lead to promising strategies in melanoma treatment, in monitoring melanoma patients, in assessing the response to immunotherapy, and in completing the standard immunohistochemical panel used in melanoma examination.",2016 Aug 24,"['Turcu, Gabriela', 'Nedelcu, Roxana Ioana', 'Ion, Daniela Adriana', 'Brînzea, Alice', 'Cioplea, Mirela Daniela', 'Jilaveanu, Lucia Beatrice', 'Zurac, Sabina Andrada']",Dis Markers,,,True
8f9e4f6b34a4b30f54abef008fc8c0fde00ff02f,PMC,"Bayesian uncertainty quantification for transmissibility of influenza, norovirus and Ebola using information geometry",http://dx.doi.org/10.1098/rsif.2016.0279,PMC5014059,27558850,CC BY,"Infectious diseases exert a large and in many contexts growing burden on human health, but violate most of the assumptions of classical epidemiological statistics and hence require a mathematically sophisticated approach. Viral shedding data are collected during human studies—either where volunteers are infected with a disease or where existing cases are recruited—in which the levels of live virus produced over time are measured. These have traditionally been difficult to analyse due to strong, complex correlations between parameters. Here, we show how a Bayesian approach to the inverse problem together with modern Markov chain Monte Carlo algorithms based on information geometry can overcome these difficulties and yield insights into the disease dynamics of two of the most prevalent human pathogens—influenza and norovirus—as well as Ebola virus disease.",2016 Aug,"['House, Thomas', 'Ford, Ashley', 'Lan, Shiwei', 'Bilson, Samuel', 'Buckingham-Jeffery, Elizabeth', 'Girolami, Mark']",J R Soc Interface,,,True
1292b5cdd7a8850cf1d0ceb1df706012c469da62,PMC,"Bayesian uncertainty quantification for transmissibility of influenza, norovirus and Ebola using information geometry",http://dx.doi.org/10.1098/rsif.2016.0279,PMC5014059,27558850,CC BY,"Infectious diseases exert a large and in many contexts growing burden on human health, but violate most of the assumptions of classical epidemiological statistics and hence require a mathematically sophisticated approach. Viral shedding data are collected during human studies—either where volunteers are infected with a disease or where existing cases are recruited—in which the levels of live virus produced over time are measured. These have traditionally been difficult to analyse due to strong, complex correlations between parameters. Here, we show how a Bayesian approach to the inverse problem together with modern Markov chain Monte Carlo algorithms based on information geometry can overcome these difficulties and yield insights into the disease dynamics of two of the most prevalent human pathogens—influenza and norovirus—as well as Ebola virus disease.",2016 Aug,"['House, Thomas', 'Ford, Ashley', 'Lan, Shiwei', 'Bilson, Samuel', 'Buckingham-Jeffery, Elizabeth', 'Girolami, Mark']",J R Soc Interface,,,True
6a1fd48435dc54d1682a0bafd6cdf7142b6b5bc4,PMC,Inferring R(0) in emerging epidemics—the effect of common population structure is small,http://dx.doi.org/10.1098/rsif.2016.0288,PMC5014060,27581480,CC BY,"When controlling an emerging outbreak of an infectious disease, it is essential to know the key epidemiological parameters, such as the basic reproduction number R(0) and the control effort required to prevent a large outbreak. These parameters are estimated from the observed incidence of new cases and information about the infectious contact structures of the population in which the disease spreads. However, the relevant infectious contact structures for new, emerging infections are often unknown or hard to obtain. Here, we show that, for many common true underlying heterogeneous contact structures, the simplification to neglect such structures and instead assume that all contacts are made homogeneously in the whole population results in conservative estimates for R(0) and the required control effort. This means that robust control policies can be planned during the early stages of an outbreak, using such conservative estimates of the required control effort.",2016 Aug,"['Trapman, Pieter', 'Ball, Frank', 'Dhersin, Jean-Stéphane', 'Tran, Viet Chi', 'Wallinga, Jacco', 'Britton, Tom']",J R Soc Interface,,,True
0b7de7591cf59d3b9e8f9db423431c0850eb0276,PMC,Inferring R(0) in emerging epidemics—the effect of common population structure is small,http://dx.doi.org/10.1098/rsif.2016.0288,PMC5014060,27581480,CC BY,"When controlling an emerging outbreak of an infectious disease, it is essential to know the key epidemiological parameters, such as the basic reproduction number R(0) and the control effort required to prevent a large outbreak. These parameters are estimated from the observed incidence of new cases and information about the infectious contact structures of the population in which the disease spreads. However, the relevant infectious contact structures for new, emerging infections are often unknown or hard to obtain. Here, we show that, for many common true underlying heterogeneous contact structures, the simplification to neglect such structures and instead assume that all contacts are made homogeneously in the whole population results in conservative estimates for R(0) and the required control effort. This means that robust control policies can be planned during the early stages of an outbreak, using such conservative estimates of the required control effort.",2016 Aug,"['Trapman, Pieter', 'Ball, Frank', 'Dhersin, Jean-Stéphane', 'Tran, Viet Chi', 'Wallinga, Jacco', 'Britton, Tom']",J R Soc Interface,,,True
cdb5b561f1c883eb82375c9c62550de77bc8b51e,PMC,"Editorial: A home for virology, ecology, epidemiology, and evolutionary biology",http://dx.doi.org/10.1093/ve/vev001,PMC5014471,27774275,CC BY,,2015 Mar 26,"['Elena, Santiago F.', 'Pybus, Oliver G.']",Virus Evol,,,True
d9ecb8e78616bebdb37e3b3b689ad60bafd922e3,PMC,Biochemical Characterization of Middle East Respiratory Syndrome Coronavirus Helicase,http://dx.doi.org/10.1128/mSphere.00235-16,PMC5014916,27631026,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) helicase is a superfamily 1 helicase containing seven conserved motifs. We have cloned, expressed, and purified a Strep-fused recombinant MERS-CoV nonstructural protein 13 (M-nsp13) helicase. Characterization of its biochemical properties showed that it unwound DNA and RNA similarly to severe acute respiratory syndrome CoV nsp13 (S-nsp13) helicase. We showed that M-nsp13 unwound in a 5′-to-3′ direction and efficiently unwound the partially duplex RNA substrates with a long loading strand relative to those of the RNA substrates with a short or no loading strand. Moreover, the K(m) of ATP for M-nsp13 is inversely proportional to the length of the 5′ loading strand of the partially duplex RNA substrates. Finally, we also showed that the rate of unwinding (ku) of M-nsp13 is directly proportional to the length of the 5′ loading strand of the partially duplex RNA substrate. These results provide insights that enhance our understanding of the biochemical properties of M-nsp13. IMPORTANCE Coronaviruses are known to cause a wide range of diseases in humans and animals. Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans in the Middle East, Europe, North Africa, and the United States of America. Helicases are motor proteins that catalyze the processive separation of double-stranded nucleic acids into two single-stranded nucleic acids by utilizing the energy derived from ATP hydrolysis. MERS-CoV helicase is one of the most important viral replication enzymes of this coronavirus. Herein, we report the first bacterial expression, enzyme purification, and biochemical characterization of MERS-CoV helicase. The knowledge obtained from this study might be used to identify an inhibitor of MERS-CoV replication, and the helicase might be used as a therapeutic target.",2016 Sep 7,"['Adedeji, Adeyemi O.', 'Lazarus, Hilary']",mSphere,,,True
810473f2145d2412461fb848c151c89a0630ca1d,PMC,Biochemical Characterization of Middle East Respiratory Syndrome Coronavirus Helicase,http://dx.doi.org/10.1128/mSphere.00235-16,PMC5014916,27631026,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) helicase is a superfamily 1 helicase containing seven conserved motifs. We have cloned, expressed, and purified a Strep-fused recombinant MERS-CoV nonstructural protein 13 (M-nsp13) helicase. Characterization of its biochemical properties showed that it unwound DNA and RNA similarly to severe acute respiratory syndrome CoV nsp13 (S-nsp13) helicase. We showed that M-nsp13 unwound in a 5′-to-3′ direction and efficiently unwound the partially duplex RNA substrates with a long loading strand relative to those of the RNA substrates with a short or no loading strand. Moreover, the K(m) of ATP for M-nsp13 is inversely proportional to the length of the 5′ loading strand of the partially duplex RNA substrates. Finally, we also showed that the rate of unwinding (ku) of M-nsp13 is directly proportional to the length of the 5′ loading strand of the partially duplex RNA substrate. These results provide insights that enhance our understanding of the biochemical properties of M-nsp13. IMPORTANCE Coronaviruses are known to cause a wide range of diseases in humans and animals. Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans in the Middle East, Europe, North Africa, and the United States of America. Helicases are motor proteins that catalyze the processive separation of double-stranded nucleic acids into two single-stranded nucleic acids by utilizing the energy derived from ATP hydrolysis. MERS-CoV helicase is one of the most important viral replication enzymes of this coronavirus. Herein, we report the first bacterial expression, enzyme purification, and biochemical characterization of MERS-CoV helicase. The knowledge obtained from this study might be used to identify an inhibitor of MERS-CoV replication, and the helicase might be used as a therapeutic target.",2016 Sep 7,"['Adedeji, Adeyemi O.', 'Lazarus, Hilary']",mSphere,,,False
f37275235174f60a5028e7d86859fecd6550f737,PMC,MicroRNA-155 enhances T cell trafficking and antiviral effector function in a model of coronavirus-induced neurologic disease,http://dx.doi.org/10.1186/s12974-016-0699-z,PMC5015201,27604627,CC BY,"BACKGROUND: MicroRNAs (miRNAs) are noncoding RNAs that modulate cellular gene expression, primarily at the post-transcriptional level. We sought to examine the functional role of miR-155 in a model of viral-induced neuroinflammation. METHODS: Acute encephalomyelitis and immune-mediated demyelination were induced by intracranial injection with the neurotropic JHM strain of mouse hepatitis virus (JHMV) into C57BL/6 miR-155(+/+) wildtype (WT) mice or miR-155(−/−) mice. Morbidity and mortality, viral load and immune cell accumulation in the CNS, and spinal cord demyelination were assessed at defined points post-infection. T cells harvested from infected mice were used to examine cytolytic activity, cytokine activity, and expression of certain chemokine receptors. To determine the impact of miR-155 on trafficking, T cells from infected WT or miR-155(−/−) mice were adoptively transferred into RAG1(−/−) mice, and T cell accumulation into the CNS was assessed using flow cytometry. Statistical significance was determined using the Mantel-Cox log-rank test or Student’s T tests. RESULTS: Compared to WT mice, JHMV-infected miR-155(−/−) mice developed exacerbated disease concomitant with increased morbidity/mortality and an inability to control viral replication within the CNS. In corroboration with increased susceptibility to disease, miR-155(−/−) mice had diminished CD8(+) T cell responses in terms of numbers, cytolytic activity, IFN-γ secretion, and homing to the CNS that corresponded with reduced expression of the chemokine receptor CXCR3. Both IFN-γ secretion and trafficking were impaired in miR-155(−/−), virus-specific CD4(+) T cells; however, expression of the chemokine homing receptors analyzed on CD4(+) cells was not affected. Except for very early during infection, there were not significant differences in macrophage infiltration into the CNS between WT and miR-155(−/−) JHMV-infected mice, and the severity of demyelination was similar at 14 days p.i. between WT and miR-155(−/−) JHMV-infected mice. CONCLUSIONS: These findings support a novel role for miR-155 in host defense in a model of viral-induced encephalomyelitis. Specifically, miR-155 enhances antiviral T cell responses including cytokine secretion, cytolytic activity, and homing to the CNS in response to viral infection. Further, miR-155 can play either a host-protective or host-damaging role during neuroinflammation depending on the disease trigger.",2016 Sep 7,"['Dickey, Laura L.', 'Worne, Colleen L.', 'Glover, Jessica L.', 'Lane, Thomas E.', 'O’Connell, Ryan M.']",J Neuroinflammation,,,True
41dc0a864ad331ec921ed5411bfdd3030859ac6f,PMC,Infectious diseases epidemic threats and mass gatherings: refocusing global attention on the continuing spread of the Middle East Respiratory syndrome coronavirus (MERS-CoV),http://dx.doi.org/10.1186/s12916-016-0686-3,PMC5015245,27604081,CC BY,"Media and World Health Organization (WHO) attention on Zika virus transmission at the 2016 Rio Olympic Games and the 2015 Ebola virus outbreak in West Africa diverted the attention of global public health authorities from other lethal infectious diseases with epidemic potential. Mass gatherings such as the annual Hajj pilgrimage hosted by Kingdom of Saudi Arabia attract huge crowds from all continents, creating high-risk conditions for the rapid global spread of infectious diseases. The highly lethal Middle Eastern respiratory syndrome coronavirus (MERS-CoV) remains in the WHO list of top emerging diseases likely to cause major epidemics. The 2015 MERS-CoV outbreak in South Korea, in which 184 MERS cases including 33 deaths occurred in 2 months, that was imported from the Middle East by a South Korean businessman was a wake-up call for the global community to refocus attention on MERS-CoV and other emerging and re-emerging infectious diseases with epidemic potential. The international donor community and Middle Eastern countries should make available resources for, and make a serious commitment to, taking forward a “One Health” global network for proactive surveillance, rapid detection, and prevention of MERS-CoV and other epidemic infectious diseases threats.",2016 Sep 7,"['Zumla, Alimuddin', 'Alagaili, Abdulaziz N.', 'Cotten, Matthew', 'Azhar, Esam I.']",BMC Med,,,True
1fceaf9f2102c71bf508ebd46c18c9b0cb48e6c3,PMC,"Morbidity, Mortality, and Seasonality of Influenza Hospitalizations in Egypt, November 2007-November 2014",http://dx.doi.org/10.1371/journal.pone.0161301,PMC5015910,27607330,CC0,"BACKGROUND: Influenza typically comprises a substantial portion of acute respiratory infections, a leading cause of mortality worldwide. However, influenza epidemiology data are lacking in Egypt. We describe seven years of Egypt’s influenza hospitalizations from a multi-site influenza surveillance system. METHODS: Syndromic case definitions identified individuals with severe acute respiratory infection (SARI) admitted to eight hospitals in Egypt. Standardized demographic and clinical data were collected. Nasopharyngeal and oropharyngeal swabs were tested for influenza using real-time reverse transcription polymerase chain reaction and typed as influenza A or B, and influenza A specimens subtyped. RESULTS: From November 2007–November 2014, 2,936/17,441 (17%) SARI cases were influenza-positive. Influenza-positive patients were more likely to be older, female, pregnant, and have chronic condition(s) (all p<0.05). Among them, 53 (2%) died, and death was associated with older age, five or more days from symptom onset to hospitalization, chronic condition(s), and influenza A (all p<0.05). An annual seasonal influenza pattern occurred from July–June. Each season, the proportion of the season’s influenza-positive cases peaked during November–May (19–41%). CONCLUSIONS: In Egypt, influenza causes considerable morbidity and mortality and influenza SARI hospitalization patterns mirror those of the Northern Hemisphere. Additional assessment of influenza epidemiology in Egypt may better guide disease control activities and vaccine policy.",2016 Sep 8,"['Kandeel, Amr', 'Dawson, Patrick', 'Labib, Manal', 'Said, Mayar', 'El-Refai, Samir', 'El-Gohari, Amani', 'Talaat, Maha']",PLoS One,,,True
e54d7c030edf8736b345a53ad17f7a7b00a74912,PMC,Negative pressure of the environmental air in the cleaning area of the materials and sterilization center: a systematic review,http://dx.doi.org/10.1590/1518-8345.1140.2781,PMC5016003,27598374,CC BY,"OBJECTIVE: to analyze the scientific evidence on aerosols generated during cleaning activities of health products in the Central Service Department (CSD) and the impact of the negative pressure of the ambient air in the cleaning area to control the dispersion of aerosols to adjacent areas. METHOD: for this literature systematic review the following searches were done: search guidelines, manuals or national and international technical standards given by experts; search in the portal and databases PubMed, Scopus, CINAHL and Web of Science; and a manual search of scientific articles. RESULTS: the five technical documents reviewed recommend that the CSD cleaning area should have a negative differential ambient air pressure, but scientific articles on the impact of this intervention were not found. The four articles included talked about aerosols formed after the use of a ultrasonic cleaner (an increased in the contamination especially during use) and pressurized water jet (formation of smaller aerosols 5μm). In a study, the aerosols formed from contaminated the hot tap water with Legionella pneumophila were evaluated. CONCLUSIONS: there is evidence of aerosol formation during cleanup activities in CSD. Studies on occupational diseases of respiratory origin of workers who work in CSD should be performed.",2016 Sep 1,"['Ciofi-Silva, Caroline Lopes', 'Hansen, Lisbeth Lima', 'Almeida, Alda Graciele Claudio dos Santos', 'Kawagoe, Julia Yaeko', 'Padoveze, Maria Clara', 'Graziano, Kazuko Uchikawa']",Rev Lat Am Enfermagem,,,True
4ed809f5b348f735454271411a4bef01bfad0734,PMC,The Quest for Anti-inflammatory and Anti-infective Biomaterials in Clinical Translation,http://dx.doi.org/10.3389/fbioe.2016.00071,PMC5016531,27668213,CC BY,"Biomaterials are now being used or evaluated clinically as implants to supplement the severe shortage of available human donor organs. To date, however, such implants have mainly been developed as scaffolds to promote the regeneration of failing organs due to old age or congenital malformations. In the real world, however, infection or immunological issues often compromise patients. For example, bacterial and viral infections can result in uncontrolled immunopathological damage and lead to organ failure. Hence, there is a need for biomaterials and implants that not only promote regeneration but also address issues that are specific to compromised patients, such as infection and inflammation. Different strategies are needed to address the regeneration of organs that have been damaged by infection or inflammation for successful clinical translation. Therefore, the real quest is for multifunctional biomaterials with combined properties that can combat infections, modulate inflammation, and promote regeneration at the same time. These strategies will necessitate the inclusion of methodologies for management of the cellular and signaling components elicited within the local microenvironment. In the development of such biomaterials, strategies range from the inclusion of materials that have intrinsic anti-inflammatory properties, such as the synthetic lipid polymer, 2-methacryloyloxyethyl phosphorylcholine (MPC), to silver nanoparticles that have antibacterial properties, to inclusion of nano- and micro-particles in biomaterials composites that deliver active drugs. In this present review, we present examples of both kinds of materials in each group along with their pros and cons. Thus, as a promising next generation strategy to aid or replace tissue/organ transplantation, an integrated smart programmable platform is needed for regenerative medicine applications to create and/or restore normal function at the cell and tissue levels. Therefore, now it is of utmost importance to develop integrative biomaterials based on multifunctional biopolymers and nanosystem for their practical and successful clinical translation.",2016 Sep 9,"['Griffith, May', 'Islam, Mohammad M.', 'Edin, Joel', 'Papapavlou, Georgia', 'Buznyk, Oleksiy', 'Patra, Hirak K.']",Front Bioeng Biotechnol,,,True
c45763bd83a192ce8ead3a628b11dd71b6e9c08a,PMC,"Zika virus: Epidemiology, current phobia and preparedness for upcoming mass gatherings, with examples from World Olympics and Pilgrimage",http://dx.doi.org/10.12669/pjms.324.10038,PMC5017074,27648063,CC BY,"OBJECTIVE: To describe Zika Virus (ZIKV) epidemiology, current phobia, and the required preparedness for its prevention during the upcoming Mass Gathering (MG) events. METHODS: Electronic databases of PubMed, WHO, CDC, Pan American Health Organization (PAHO), Google, and Cochrane library were extensively searched for ZIKV. Articles were reviewed, scrutinized and critically appraised and the most relevant articles were utilized. RESULTS: ZIKV is an emerging Flavivirus which was first isolated from Uganda in 1947. It is transmitted mainly through bite of Aedes mosquitoes. Sexual, perinatal and blood-borne transmissions are implicated. ZIKV is incriminated to cause microcephaly and Guillain-Barré syndrome. The spiky spread of ZIKV and its epidemic potential are especially problematic in countries which host big MGs with endogenous ZIKV circulation. This put millions of international travelers and local inhabitants at risk of acquiring ZIKV, especially in absence of vaccine until now. Brazil Olympic and Paralympics Games, and Muslims Hajj in Saudi Arabia are important upcoming MGs. Regarding Brazil, swiftly epidemic of ZIKV causes phobia and provokes claims and counter-claims about possible postponing or cancellation of such events. RECOMMENDATIONS: Intensifying ZIKV epidemiological surveillance (sentinel, syndromic, environmental, laboratory and electronic), and conduction of educational programs are required. Controlling Aedes vector (chemically & biologically) is essential. Multidisciplinary cooperation is required to win the war against ZIKV.",2016 Jul-Aug,"Ibrahim, Nahla Khamis",Pak J Med Sci,,,True
1af9746ea8f584f3f58da4f59d6dba8185f8be4b,PMC,Building Ventilation as an Effective Disease Intervention Strategy in a Dense Indoor Contact Network in an Ideal City,http://dx.doi.org/10.1371/journal.pone.0162481,PMC5017609,27611368,CC BY,"Emerging diseases may spread rapidly through dense and large urban contact networks, especially they are transmitted by the airborne route, before new vaccines can be made available. Airborne diseases may spread rapidly as people visit different indoor environments and are in frequent contact with others. We constructed a simple indoor contact model for an ideal city with 7 million people and 3 million indoor spaces, and estimated the probability and duration of contact between any two individuals during one day. To do this, we used data from actual censuses, social behavior surveys, building surveys, and ventilation measurements in Hong Kong to define eight population groups and seven indoor location groups. Our indoor contact model was integrated with an existing epidemiological Susceptible, Exposed, Infectious, and Recovered (SEIR) model to estimate disease spread and with the Wells-Riley equation to calculate local infection risks, resulting in an integrated indoor transmission network model. This model was used to estimate the probability of an infected individual infecting others in the city and to study the disease transmission dynamics. We predicted the infection probability of each sub-population under different ventilation systems in each location type in the case of a hypothetical airborne disease outbreak, which is assumed to have the same natural history and infectiousness as smallpox. We compared the effectiveness of controlling ventilation in each location type with other intervention strategies. We conclude that increasing building ventilation rates using methods such as natural ventilation in classrooms, offices, and homes is a relatively effective strategy for airborne diseases in a large city.",2016 Sep 9,"['Gao, Xiaolei', 'Wei, Jianjian', 'Lei, Hao', 'Xu, Pengcheng', 'Cowling, Benjamin J.', 'Li, Yuguo']",PLoS One,,,True
702157bbe24c5eca7ab92f90cd717c3e56aa6ccf,PMC,Building Ventilation as an Effective Disease Intervention Strategy in a Dense Indoor Contact Network in an Ideal City,http://dx.doi.org/10.1371/journal.pone.0162481,PMC5017609,27611368,CC BY,"Emerging diseases may spread rapidly through dense and large urban contact networks, especially they are transmitted by the airborne route, before new vaccines can be made available. Airborne diseases may spread rapidly as people visit different indoor environments and are in frequent contact with others. We constructed a simple indoor contact model for an ideal city with 7 million people and 3 million indoor spaces, and estimated the probability and duration of contact between any two individuals during one day. To do this, we used data from actual censuses, social behavior surveys, building surveys, and ventilation measurements in Hong Kong to define eight population groups and seven indoor location groups. Our indoor contact model was integrated with an existing epidemiological Susceptible, Exposed, Infectious, and Recovered (SEIR) model to estimate disease spread and with the Wells-Riley equation to calculate local infection risks, resulting in an integrated indoor transmission network model. This model was used to estimate the probability of an infected individual infecting others in the city and to study the disease transmission dynamics. We predicted the infection probability of each sub-population under different ventilation systems in each location type in the case of a hypothetical airborne disease outbreak, which is assumed to have the same natural history and infectiousness as smallpox. We compared the effectiveness of controlling ventilation in each location type with other intervention strategies. We conclude that increasing building ventilation rates using methods such as natural ventilation in classrooms, offices, and homes is a relatively effective strategy for airborne diseases in a large city.",2016 Sep 9,"['Gao, Xiaolei', 'Wei, Jianjian', 'Lei, Hao', 'Xu, Pengcheng', 'Cowling, Benjamin J.', 'Li, Yuguo']",PLoS One,,,True
ea007e00fc6123e617913bd68cd8b54c4f0b111a,PMC,Viral Infection of the Central Nervous System Exacerbates Interleukin-10 Receptor Deficiency-Mediated Colitis in SJL Mice,http://dx.doi.org/10.1371/journal.pone.0161883,PMC5017624,27611574,CC BY,"Theiler´s murine encephalomyelitis virus (TMEV)-infection is a widely used animal model for studying demyelinating disorders, including multiple sclerosis (MS). The immunosuppressive cytokine Interleukin (IL)-10 counteracts hyperactive immune responses and critically controls immune homeostasis in infectious and autoimmune disorders. In order to investigate the effect of signaling via Interleukin-10 receptor (IL-10R) in infectious neurological diseases, TMEV-infected SJL mice were treated with IL-10R blocking antibody (Ab) in the acute and chronic phase of the disease. The findings demonstrate that (i) Ab-mediated IL-10 neutralization leads to progressive colitis with a reduction in Foxp3(+) regulatory T cells and increased numbers of CD8(+)CD44(+) memory T cells as well as activated CD4(+)CD69(+) and CD8(+)CD69(+) T cells in uninfected mice. (ii) Concurrent acute TMEV-infection worsened enteric disease-mediated by IL-10R neutralization. Virus-triggered effects were associated with an enhanced activation of CD4(+) T helper cells and CD8(+) cytotoxic T lymphocytes and augmented cytokine expression. By contrast, (iii) IL-10R neutralization during chronic TMEV-infection was not associated with enhanced peripheral immunopathology but an increased CD3(+) T cell influx in the spinal cord. IL-10R neutralization causes a breakdown in peripheral immune tolerance in genetically predisposed mice, which leads to immune-mediated colitis, resembling inflammatory bowel disease. Hyperactive immune state following IL-10R blockade is enhanced by central nervous system-restricted viral infection in a disease phase-dependent manner.",2016 Sep 9,"['Uhde, Ann-Kathrin', 'Herder, Vanessa', 'Akram Khan, Muhammad', 'Ciurkiewicz, Malgorzata', 'Schaudien, Dirk', 'Teich, René', 'Floess, Stefan', 'Baumgärtner, Wolfgang', 'Huehn, Jochen', 'Beineke, Andreas']",PLoS One,,,True
7b7e0cb6554d2f871d6b09daa0b5505472873a20,PMC,Mumps Virus: Modification of the Identify-Isolate-Inform Tool for Frontline Healthcare Providers,http://dx.doi.org/10.5811/westjem.2016.6.30793,PMC5017829,27625709,CC BY,"Mumps is a highly contagious viral infection that became rare in most industrialized countries following the introduction of measles-mumps-rubella (MMR) vaccine in 1967. The disease, however, has been re-emerging with several outbreaks over the past decade. Many clinicians have never seen a case of mumps. To assist frontline healthcare providers with detecting potential cases and initiating critical actions, investigators modified the “Identify-Isolate-Inform” tool for mumps infection. The tool is applicable to regions with rare incidences or local outbreaks, especially seen in college students, as well as globally in areas where vaccination is less common. Mumps begins with a prodrome of low-grade fever, myalgias and malaise/anorexia, followed by development of nonsuppurative parotitis, which is the pathognomonic finding associated with acute mumps infection. Orchitis and meningitis are the two most common serious complications, with hearing loss and infertility occurring rarely. Providers should consider mumps in patients with exposure to a known case or international travel to endemic regions who present with consistent signs and symptoms. If mumps is suspected, healthcare providers must immediately implement standard and droplet precautions and notify the local health department and hospital infection control personnel.",2016 Sep 30,"['Koenig, Kristi L.', 'Shastry, Siri', 'Mzahim, Bandr', 'Almadhyan, Abdulmajeed', 'Burns, Michael J.']",West J Emerg Med,,,True
4aa6c6d082407bee2de3cfdc3a8a11a229904fda,PMC,The multifaceted role of astrocytes in regulating myelination,http://dx.doi.org/10.1016/j.expneurol.2016.03.009,PMC5019113,26988764,CC BY,"Astrocytes are the major glial cell of the central nervous system (CNS), providing both metabolic and physical support to other neural cells. After injury, astrocytes become reactive and express a continuum of phenotypes which may be supportive or inhibitory to CNS repair. This review will focus on the ability of astrocytes to influence myelination in the context of specific secreted factors, cytokines and other neural cell targets within the CNS. In particular, we focus on how astrocytes provide energy and cholesterol to neurons, influence synaptogenesis, affect oligodendrocyte biology and instigate cross-talk between the many cellular components of the CNS.",2016 Sep,"['Kıray, Hülya', 'Lindsay, Susan L.', 'Hosseinzadeh, Sara', 'Barnett, Susan C.']",Exp Neurol,,,False
4d1696e014e57ca335e9fe116840afda273d2ba9,PMC,Etiology and Clinical Characteristics of Single and Multiple Respiratory Virus Infections Diagnosed in Croatian Children in Two Respiratory Seasons,http://dx.doi.org/10.1155/2016/2168780,PMC5021477,27656298,CC BY,"The aim of this study was to determine the causative agent of acute respiratory infection (ARI) in hospitalized children, as well as investigate the characteristics of ARIs with single and multiple virus detection in two respiratory seasons. In 2010 and 2015, nasopharyngeal and pharyngeal swabs from a total of 134 children, admitted to the hospital due to ARI, were tested using multiplex PCR. Viral etiology was established in 81.3% of the patients. Coinfection with two viruses was diagnosed in 27.6% of the patients, and concurrent detection of three or more viruses was diagnosed in 12.8% of the patients. The most commonly diagnosed virus in both seasons combined was respiratory syncytial virus (RSV) (28.6%), followed by parainfluenza viruses (PIVs) types 1–3 (18.4%), rhinovirus (HRV) (14.3%), human metapneumovirus (10.1%), adenovirus (AdV) (7.1%), influenza viruses types A and B (4.8%), and coronaviruses (4.2%). In 2015, additional pathogens were investigated with the following detection rate: enterovirus (13.2%), bocavirus (HBoV) (10.5%), PIV-4 (2.6%), and parechovirus (1.3%). There were no statistical differences between single and multiple virus infection regarding patients age, localization of infection, and severity of disease (P > 0.05). AdV, HRV, HBoV, and PIVs were significantly more often detected in multiple virus infections compared to the other respiratory viruses (P < 0.001).",2016 Aug 30,"['Ljubin-Sternak, Sunčanica', 'Marijan, Tatjana', 'Ivković-Jureković, Irena', 'Čepin-Bogović, Jasna', 'Gagro, Alenka', 'Vraneš, Jasmina']",J Pathog,,,True
12d7a96036ca9e861d3636d55d3841452e455c73,PMC,Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors,http://dx.doi.org/10.1371/journal.pone.0162178,PMC5023107,27627440,CC BY,"We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs). During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant), bacteremia, urinary tract infection (UTI), respiratory virus infection, and varicella zoster virus (VZV) reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant), bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection). Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children.",2016 Sep 14,"['Choi, Young Bae', 'Yi, Eun Sang', 'Kang, Ji-Man', 'Lee, Ji Won', 'Yoo, Keon Hee', 'Kim, Yae-Jean', 'Sung, Ki Woong', 'Koo, Hong Hoe']",PLoS One,,,True
51448d629c1d530b3001bc292c2d819a71ecdf23,PMC,A GeXP-Based Assay for Simultaneous Detection of Multiple Viruses in Hospitalized Children with Community Acquired Pneumonia,http://dx.doi.org/10.1371/journal.pone.0162411,PMC5023126,27627439,CC BY,"The GeXP-based assay has recently been developed for simultaneous detection of multiple pathogens. So far, the application of the GeXP assay to test larger clinical samples has hardly been reported. Community-acquired pneumonia (CAP) is the leading cause of death in children worldwide and a substantial proportion of childhood CAP is caused by viruses. Rapid and accurate diagnosis of virus infection is important for the clinical management of CAP. In this study, we explored the GeXP assay for simultaneous detection of 20 types/subtypes of viruses in hospitalized children with CAP. A total of 1699 nasopharyngeal swabs were prospectively collected and viral nucleic acid was extracted and assayed. Using viral genomic DNA or RNA as template, we showed that at the concentration of 10(4) copies of DNA or RNA of each virus/μl, all 20 target viruses were simultaneously identified by the GeXP assay. Fifteen control microorganisms, in contrast, failed to be amplified by the assay. About 65% of cases tested in this study had viral infection, with patients aged <3 years having a 70% positive rate, significantly higher than that in patients aged > 3 years (40%). The most frequently detected virus was RSV followed by PIV3, HRV, ADV and HBoV. Seasonal distribution analysis revealed that RSV was the most predominant in autumn and winter, while in spring and summer PIV3 and RSV were the most frequently identified with similar positive percentages. One hundred twenty randomly-chosen samples tested by the GeXP assay were re-evaluated by mono-RT-PCR, the results showed 97.5% diagnosis agreement between these 2 methods. Our findings suggest that the GeXP assay could be a valuable diagnostic tool for virus infection in pediatric patients with CAP.",2016 Sep 14,"['Wang, Le', 'Zhao, Mengchuan', 'Shi, Zhongren', 'Feng, Zhishan', 'Guo, Weiwei', 'Yang, Shuo', 'Liu, Lanping', 'Li, Guixia']",PLoS One,,,True
1a29f97fc037ea6456b41d054e5603fbd4f76e94,PMC,Presence of Vaccine-Derived Newcastle Disease Viruses in Wild Birds,http://dx.doi.org/10.1371/journal.pone.0162484,PMC5023329,27626272,CC0,"Our study demonstrates the repeated isolation of vaccine-derived Newcastle disease viruses from different species of wild birds across four continents from 1997 through 2014. The data indicate that at least 17 species from ten avian orders occupying different habitats excrete vaccine-derived Newcastle disease viruses. The most frequently reported isolates were detected among individuals in the order Columbiformes (n = 23), followed in frequency by the order Anseriformes (n = 13). Samples were isolated from both free-ranging (n = 47) and wild birds kept in captivity (n = 7). The number of recovered vaccine-derived viruses corresponded with the most widely utilized vaccines, LaSota (n = 28) and Hitchner B1 (n = 19). Other detected vaccine-derived viruses resembled the PHY-LMV2 and V4 vaccines, with five and two cases, respectively. These results and the ubiquitous and synanthropic nature of wild pigeons highlight their potential role as indicator species for the presence of Newcastle disease virus of low virulence in the environment. The reverse spillover of live agents from domestic animals to wildlife as a result of the expansion of livestock industries employing massive amounts of live virus vaccines represent an underappreciated and poorly studied effect of human activity on wildlife.",2016 Sep 14,"['Ayala, Andrea J.', 'Dimitrov, Kiril M.', 'Becker, Cassidy R.', 'Goraichuk, Iryna V.', 'Arns, Clarice W.', 'Bolotin, Vitaly I.', 'Ferreira, Helena L.', 'Gerilovych, Anton P.', 'Goujgoulova, Gabriela V.', 'Martini, Matheus C.', 'Muzyka, Denys V.', 'Orsi, Maria A.', 'Scagion, Guilherme P.', 'Silva, Renata K.', 'Solodiankin, Olexii S.', 'Stegniy, Boris T.', 'Miller, Patti J.', 'Afonso, Claudio L.']",PLoS One,,,True
acb8ae819eaf658a9e9704220f1e987a0365675e,PMC,Monocytes and B cells support active replication of Chandipura virus,http://dx.doi.org/10.1186/s12879-016-1794-6,PMC5024506,27628855,CC BY,"BACKGROUND: Interaction between immune system and Chandipura virus (CHPV) during different stages of its life cycle remain poorly understood. The exact route of virus entry into the blood and CNS invasion has not been clearly defined. The present study was undertaken to assess the population in PBMC that supports the growth of virus and to detect active virus replication in PBMC as well as its subsets. METHODS: PBMC subsets viz.: CD3(+), CD14(+), CD19(+), CD56(+)cells were separated and infected with CHPV. The infected cells were then assessed for transcription (N gene primer) and replication (NP gene primer) of CHPV by PCR. The supernatant collected from infected cells were titrated in Baby Hamster Kidney (BHK) cells to assess virus release. The cytokine and chemokine expression was quantified by flow cytometry. RESULTS: Amplification of N and NP gene was detected in CD14(+) (monocyte) and CD19(+) (B cell), significant increase in virus titre was also observed in these subsets. It was observed that, although the levels of IL-6 and IL-10 were elevated in CD14(+) cells as compared to CD19(+)cells, the differences were not significant. However the levels of TNFα and IL-8 were significantly elevated in CD14(+) cells than in CD19(+)cells. The levels of chemokine (CXCL9, CCL5, CCL2, CXCL10) were significantly elevated in CHPV infected PBMC as compared to uninfected cells. CCL2 and CXCL9 were significantly increased in CHPV infected CD14(+)cells as compared to CD19(+) cells. CONCLUSION: CD14(+)and CD19(+)cells support active replication of CHPV. High viral load was detected in CD14(+) cells infected with CHPV hence it might be the primary target cells for active replication of CHPV. An elevated levels of cytokines and chemokines observed in CD14(+) cells may help in predicting the pathogenecity of CHPV and possible entry into the central nervous system.",2016 Sep 14,"['Roy, Soumen', 'Pavitrakar, Daya', 'Gunjikar, Rashmi', 'Ayachit, Vijay M.', 'Bondre, Vijay P.', 'Sapkal, Gajanan N.']",BMC Infect Dis,,,True
132d356a5461491379ccfb628fca604ef66b53e2,PMC,Influenza B virus non-structural protein 1 counteracts ISG15 antiviral activity by sequestering ISGylated viral proteins,http://dx.doi.org/10.1038/ncomms12754,PMC5025834,27587337,CC BY,"The ubiquitin-like protein ISG15 and its conjugation to proteins (ISGylation) are strongly induced by type I interferon. Influenza B virus encodes non-structural protein 1 (NS1B) that binds human ISG15 and provides an appropriate model for determining how ISGylation affects virus replication in human cells. Here using a recombinant virus encoding a NS1B protein defective in ISG15 binding, we show that NS1B counteracts ISGylation-mediated antiviral activity by binding and sequestering ISGylated viral proteins, primarily ISGylated viral nucleoprotein (NP), in infected cells. ISGylated NP that is not sequestered by mutant NS1B acts as a dominant-negative inhibitor of oligomerization of the more abundant unconjugated NP. Consequently formation of viral ribonucleoproteins that catalyse viral RNA synthesis is inhibited, causing decreased viral protein synthesis and virus replication. We verify that ISGylated NP is largely responsible for inhibition of viral RNA synthesis by generating recombinant viruses that lack known ISGylation sites in NP.",2016 Sep 2,"['Zhao, Chen', 'Sridharan, Haripriya', 'Chen, Ran', 'Baker, Darren P.', 'Wang, Shanshan', 'Krug, Robert M.']",Nat Commun,,,True
53fa60a93898a5901b87fe8ad651ac5f75611071,PMC,Influenza B virus non-structural protein 1 counteracts ISG15 antiviral activity by sequestering ISGylated viral proteins,http://dx.doi.org/10.1038/ncomms12754,PMC5025834,27587337,CC BY,"The ubiquitin-like protein ISG15 and its conjugation to proteins (ISGylation) are strongly induced by type I interferon. Influenza B virus encodes non-structural protein 1 (NS1B) that binds human ISG15 and provides an appropriate model for determining how ISGylation affects virus replication in human cells. Here using a recombinant virus encoding a NS1B protein defective in ISG15 binding, we show that NS1B counteracts ISGylation-mediated antiviral activity by binding and sequestering ISGylated viral proteins, primarily ISGylated viral nucleoprotein (NP), in infected cells. ISGylated NP that is not sequestered by mutant NS1B acts as a dominant-negative inhibitor of oligomerization of the more abundant unconjugated NP. Consequently formation of viral ribonucleoproteins that catalyse viral RNA synthesis is inhibited, causing decreased viral protein synthesis and virus replication. We verify that ISGylated NP is largely responsible for inhibition of viral RNA synthesis by generating recombinant viruses that lack known ISGylation sites in NP.",2016 Sep 2,"['Zhao, Chen', 'Sridharan, Haripriya', 'Chen, Ran', 'Baker, Darren P.', 'Wang, Shanshan', 'Krug, Robert M.']",Nat Commun,,,True
3256ad6795fb323a3711f3d3d6f7ae85657fc5ff,PMC,Biochemical and structural characterization of the interface mediating interaction between the influenza A virus non-structural protein-1 and a monoclonal antibody,http://dx.doi.org/10.1038/srep33382,PMC5025888,27633136,CC BY,"We have previously shown that a non-structural protein 1 (NS1)-binding monoclonal antibody, termed as 2H6, can significantly reduce influenza A virus (IAV) replication when expressed intracellularly. In this study, we further showed that 2H6 binds stronger to the NS1 of H5N1 than A/Puerto Rico/8/1934(H1N1) because of an amino acid difference at residue 48. A crystal structure of 2H6 fragment antigen-binding (Fab) has also been solved and docked onto the NS1 structure to reveal the contacts between specific residues at the interface of antibody-antigen complex. In one of the models, the predicted molecular contacts between residues in NS1 and 2H6-Fab correlate well with biochemical results. Taken together, residues N48 and T49 in H5N1 NS1 act cooperatively to maintain a strong interaction with mAb 2H6 by forming hydrogen bonds with residues found in the heavy chain of the antibody. Interestingly, the pandemic H1N1-2009 and the majority of seasonal H3N2 circulating in humans since 1968 has N48 in NS1, suggesting that mAb 2H6 could bind to most of the currently circulating seasonal influenza A virus strains. Consistent with the involvement of residue T49, which is well-conserved, in RNA binding, mAb 2H6 was also found to inhibit the interaction between NS1 and double-stranded RNA.",2016 Sep 16,"['Wu, Jianping', 'Mok, Chee-Keng', 'Chow, Vincent Tak Kwong', 'Yuan, Y. Adam', 'Tan, Yee-Joo']",Sci Rep,,,True
4468cfd09ed3ad64822cc4fc843b2bea5684cc46,PMC,Biochemical and structural characterization of the interface mediating interaction between the influenza A virus non-structural protein-1 and a monoclonal antibody,http://dx.doi.org/10.1038/srep33382,PMC5025888,27633136,CC BY,"We have previously shown that a non-structural protein 1 (NS1)-binding monoclonal antibody, termed as 2H6, can significantly reduce influenza A virus (IAV) replication when expressed intracellularly. In this study, we further showed that 2H6 binds stronger to the NS1 of H5N1 than A/Puerto Rico/8/1934(H1N1) because of an amino acid difference at residue 48. A crystal structure of 2H6 fragment antigen-binding (Fab) has also been solved and docked onto the NS1 structure to reveal the contacts between specific residues at the interface of antibody-antigen complex. In one of the models, the predicted molecular contacts between residues in NS1 and 2H6-Fab correlate well with biochemical results. Taken together, residues N48 and T49 in H5N1 NS1 act cooperatively to maintain a strong interaction with mAb 2H6 by forming hydrogen bonds with residues found in the heavy chain of the antibody. Interestingly, the pandemic H1N1-2009 and the majority of seasonal H3N2 circulating in humans since 1968 has N48 in NS1, suggesting that mAb 2H6 could bind to most of the currently circulating seasonal influenza A virus strains. Consistent with the involvement of residue T49, which is well-conserved, in RNA binding, mAb 2H6 was also found to inhibit the interaction between NS1 and double-stranded RNA.",2016 Sep 16,"['Wu, Jianping', 'Mok, Chee-Keng', 'Chow, Vincent Tak Kwong', 'Yuan, Y. Adam', 'Tan, Yee-Joo']",Sci Rep,,,False
d0d47cee33a4e690e05f6277dd513682b7d35bdb,PMC,Immunogenicity of RSV F DNA Vaccine in BALB/c Mice,http://dx.doi.org/10.1155/2016/7971847,PMC5027326,27688769,CC BY,"Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease leading to numerous hospitalizations and deaths among the infant and elderly populations worldwide. There is no vaccine or a less effective drug available against RSV infections. Natural RSV infection stimulates the Th1 immune response and activates the production of neutralizing antibodies, while earlier vaccine trials that used UV-inactivated RSV exacerbated the disease due to the activation of the allergic Th2 response. With a focus on Th1 immunity, we developed a DNA vaccine containing the native RSV fusion (RSV F) protein and studied its immune response in BALB/c mice. High levels of RSV specific antibodies were induced during subsequent immunizations. The serum antibodies were able to neutralize RSV in vitro. The RSV inhibition by sera was also shown by immunofluorescence analyses. Antibody response of the RSV F DNA vaccine showed a strong Th1 response. Also, sera from RSV F immunized and RSV infected mice reduced the RSV infection by 50% and 80%, respectively. Our data evidently showed that the RSV F DNA vaccine activated the Th1 biased immune response and led to the production of neutralizing antibodies, which is the desired immune response required for protection from RSV infections.",2016 Sep 5,"['Eroglu, Erdal', 'Singh, Ankur', 'Bawage, Swapnil', 'Tiwari, Pooja M.', 'Vig, Komal', 'Pillai, Shreekumar R.', 'Dennis, Vida A.', 'Singh, Shree R.']",Adv Virol,,,True
0022796bb2112abd2e6423ba2d57751db06049fb,PMC,Public Health Responses to and Challenges for the Control of Dengue Transmission in High-Income Countries: Four Case Studies,http://dx.doi.org/10.1371/journal.pntd.0004943,PMC5028037,27643596,CC BY,"Dengue has a negative impact in low- and lower middle-income countries, but also affects upper middle- and high-income countries. Despite the efforts at controlling this disease, it is unclear why dengue remains an issue in affluent countries. A better understanding of dengue epidemiology and its burden, and those of chikungunya virus and Zika virus which share vectors with dengue, is required to prevent the emergence of these diseases in high-income countries in the future. The purpose of this review was to assess the relative burden of dengue in four high-income countries and to appraise the similarities and differences in dengue transmission. We searched PubMed, ISI Web of Science, and Google Scholar using specific keywords for articles published up to 05 May 2016. We found that outbreaks rarely occur where only Aedes albopictus is present. The main similarities between countries uncovered by our review are the proximity to dengue-endemic countries, the presence of a competent mosquito vector, a largely nonimmune population, and a lack of citizens’ engagement in control of mosquito breeding. We identified important epidemiological and environmental issues including the increase of local transmission despite control efforts, population growth, difficulty locating larval sites, and increased human mobility from neighboring endemic countries. Budget cuts in health and lack of practical vaccines contribute to an increased risk. To be successful, dengue-control programs for high-income countries must consider the epidemiology of dengue in other countries and use this information to minimize virus importation, improve the control of the cryptic larval habitat, and engage the community in reducing vector breeding. Finally, the presence of a communicable disease center is critical for managing and reducing future disease risks.",2016 Sep 19,"['Viennet, Elvina', 'Ritchie, Scott A.', 'Williams, Craig R.', 'Faddy, Helen M.', 'Harley, David']",PLoS Negl Trop Dis,,,True
8b71af2afcb6a76e746d1a9d77d018d28efd4969,PMC,Transcriptomic Analysis of Persistent Infection with Foot-and-Mouth Disease Virus in Cattle Suggests Impairment of Apoptosis and Cell-Mediated Immunity in the Nasopharynx,http://dx.doi.org/10.1371/journal.pone.0162750,PMC5028045,27643611,CC0,"In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vaccine, 10 non-vaccinated) were challenged with FMDV A(24) Cruzeiro, and the gene expression profiles of nasopharyngeal tissues collected between 21 and 35 days after challenge were compared between 11 persistently infected carriers and 7 non-carriers. Carriers and non-carriers were further compared to 2 naïve animals that had been neither vaccinated nor challenged. At a controlled false-discovery rate of 10% and a minimum difference in expression of 50%, 648 genes were differentially expressed between FMDV carriers and non-carriers, and most (467) had higher expression in carriers. Among these, genes associated with cellular proliferation and the immune response–such as chemokines, cytokines and genes regulating T and B cells–were significantly overrepresented. Differential gene expression was significantly correlated between non-vaccinated and vaccinated animals (biological correlation +0.97), indicating a similar transcriptome profile across these groups. Genes related to prostaglandin E(2) production and the induction of regulatory T cells were overexpressed in carriers. In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-apoptotic genes that could promote virus clearance. Based on these findings, we propose a working hypothesis for FMDV persistence in nasopharyngeal tissues of cattle, in which the virus may be maintained by an impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatory T cells.",2016 Sep 19,"['Eschbaumer, Michael', 'Stenfeldt, Carolina', 'Smoliga, George R.', 'Pacheco, Juan M.', 'Rodriguez, Luis L.', 'Li, Robert W.', 'Zhu, James', 'Arzt, Jonathan']",PLoS One,,,True
73068e027281777c2e06dfc12d03b082b46e9536,PMC,Transcriptomic Analysis of Persistent Infection with Foot-and-Mouth Disease Virus in Cattle Suggests Impairment of Apoptosis and Cell-Mediated Immunity in the Nasopharynx,http://dx.doi.org/10.1371/journal.pone.0162750,PMC5028045,27643611,CC0,"In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vaccine, 10 non-vaccinated) were challenged with FMDV A(24) Cruzeiro, and the gene expression profiles of nasopharyngeal tissues collected between 21 and 35 days after challenge were compared between 11 persistently infected carriers and 7 non-carriers. Carriers and non-carriers were further compared to 2 naïve animals that had been neither vaccinated nor challenged. At a controlled false-discovery rate of 10% and a minimum difference in expression of 50%, 648 genes were differentially expressed between FMDV carriers and non-carriers, and most (467) had higher expression in carriers. Among these, genes associated with cellular proliferation and the immune response–such as chemokines, cytokines and genes regulating T and B cells–were significantly overrepresented. Differential gene expression was significantly correlated between non-vaccinated and vaccinated animals (biological correlation +0.97), indicating a similar transcriptome profile across these groups. Genes related to prostaglandin E(2) production and the induction of regulatory T cells were overexpressed in carriers. In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-apoptotic genes that could promote virus clearance. Based on these findings, we propose a working hypothesis for FMDV persistence in nasopharyngeal tissues of cattle, in which the virus may be maintained by an impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatory T cells.",2016 Sep 19,"['Eschbaumer, Michael', 'Stenfeldt, Carolina', 'Smoliga, George R.', 'Pacheco, Juan M.', 'Rodriguez, Luis L.', 'Li, Robert W.', 'Zhu, James', 'Arzt, Jonathan']",PLoS One,,,False
933bde921b806a7157fe084a0256ed26d394e8cd,PMC,Transcriptomic Analysis of Persistent Infection with Foot-and-Mouth Disease Virus in Cattle Suggests Impairment of Apoptosis and Cell-Mediated Immunity in the Nasopharynx,http://dx.doi.org/10.1371/journal.pone.0162750,PMC5028045,27643611,CC0,"In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vaccine, 10 non-vaccinated) were challenged with FMDV A(24) Cruzeiro, and the gene expression profiles of nasopharyngeal tissues collected between 21 and 35 days after challenge were compared between 11 persistently infected carriers and 7 non-carriers. Carriers and non-carriers were further compared to 2 naïve animals that had been neither vaccinated nor challenged. At a controlled false-discovery rate of 10% and a minimum difference in expression of 50%, 648 genes were differentially expressed between FMDV carriers and non-carriers, and most (467) had higher expression in carriers. Among these, genes associated with cellular proliferation and the immune response–such as chemokines, cytokines and genes regulating T and B cells–were significantly overrepresented. Differential gene expression was significantly correlated between non-vaccinated and vaccinated animals (biological correlation +0.97), indicating a similar transcriptome profile across these groups. Genes related to prostaglandin E(2) production and the induction of regulatory T cells were overexpressed in carriers. In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-apoptotic genes that could promote virus clearance. Based on these findings, we propose a working hypothesis for FMDV persistence in nasopharyngeal tissues of cattle, in which the virus may be maintained by an impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatory T cells.",2016 Sep 19,"['Eschbaumer, Michael', 'Stenfeldt, Carolina', 'Smoliga, George R.', 'Pacheco, Juan M.', 'Rodriguez, Luis L.', 'Li, Robert W.', 'Zhu, James', 'Arzt, Jonathan']",PLoS One,,,False
d096bbd29d25374aa7fea667ac750e5739370dcf,PMC,A systematic view on influenza induced host shutoff,http://dx.doi.org/10.7554/eLife.18311,PMC5028189,27525483,CC BY,"Host shutoff is a common strategy used by viruses to repress cellular mRNA translation and concomitantly allow the efficient translation of viral mRNAs. Here we use RNA-sequencing and ribosome profiling to explore the mechanisms that are being utilized by the Influenza A virus (IAV) to induce host shutoff. We show that viral transcripts are not preferentially translated and instead the decline in cellular protein synthesis is mediated by viral takeover on the mRNA pool. Our measurements also uncover strong variability in the levels of cellular transcripts reduction, revealing that short transcripts are less affected by IAV. Interestingly, these mRNAs that are refractory to IAV infection are enriched in cell maintenance processes such as oxidative phosphorylation. Furthermore, we show that the continuous oxidative phosphorylation activity is important for viral propagation. Our results advance our understanding of IAV-induced shutoff, and suggest a mechanism that facilitates the translation of genes with important housekeeping functions. DOI: http://dx.doi.org/10.7554/eLife.18311.001",,"['Bercovich-Kinori, Adi', 'Tai, Julie', 'Gelbart, Idit Anna', 'Shitrit, Alina', 'Ben-Moshe, Shani', 'Drori, Yaron', 'Itzkovitz, Shalev', 'Mandelboim, Michal', 'Stern-Ginossar, Noam']",eLife.; 5:e18311,,,True
96a1e9e95b2ab796897177f18a1d3e148b83e57e,PMC,The evidence of porcine hemagglutinating encephalomyelitis virus induced nonsuppurative encephalitis as the cause of death in piglets,http://dx.doi.org/10.7717/peerj.2443,PMC5028786,27672502,CC BY,"An acute outbreak of porcine hemagglutinating encephalomyelitis virus (PHEV) infection in piglets, characterized with neurological symptoms, vomiting, diarrhea, and wasting, occurred in China. Coronavirus-like particles were observed in the homogenized tissue suspensions of the brain of dead piglets by electron microscopy, and a wild PHEV strain was isolated, characterized, and designated as PHEV-CC14. Histopathologic examinations of the dead piglets showed characteristics of non-suppurative encephalitis, and some neurons in the cerebral cortex were degenerated and necrotic, and neuronophagia. Similarly, mice inoculated with PHEV-CC14 were found to have central nervous system (CNS) dysfunction, with symptoms of depression, arched waists, standing and vellicating front claws. Furthmore, PHEV-positive labeling of neurons in cortices of dead piglets and infected mice supported the viral infections of the nervous system. Then, the major structural genes of PHEV-CC14 were sequenced and phylogenetically analyzed, and the strain shared 95%–99.2% nt identity with the other PHEV strains available in GenBank. Phylogenetic analysis clearly proved that the wild strain clustered into a subclass with a HEV-JT06 strain. These findings suggested that the virus had a strong tropism for CNS, in this way, inducing nonsuppurative encephalitis as the cause of death in piglets. Simultaneously, the predicted risk of widespread transmission showed a certain variation among the PHEV strains currently circulating around the world. Above all, the information presented in this study can not only provide good reference for the experimental diagnosis of PHEV infection for pig breeding, but also promote its new effective vaccine development.",2016 Sep 15,"['Li, Zi', 'He, Wenqi', 'Lan, Yungang', 'Zhao, Kui', 'Lv, Xiaoling', 'Lu, Huijun', 'Ding, Ning', 'Zhang, Jing', 'Shi, Junchao', 'Shan, Changjian', 'Gao, Feng']",PeerJ,,,True
6d1b4e1200c1da4dff5048bdff36805e28511154,PMC,Cats are not small dogs: is there an immunological explanation for why cats are less affected by arthropod-borne disease than dogs?,http://dx.doi.org/10.1186/s13071-016-1798-5,PMC5028948,27646278,CC BY,"It is widely recognized that cats appear to be less frequently affected by arthropod-borne infectious diseases than dogs and share fewer zoonotic pathogens with man. This impression is supported by the relative lack of scientific publications related to feline vector-borne infections. This review explores the possible reasons for the difference between the two most common small companion animal species, including the hypothesis that cats might have a genetically-determined immunological resistance to arthropod vectors or the microparasites they transmit. A number of simple possibilities might account for the lower prevalence of these diseases in cats, including factors related to the lifestyle and behaviour of the cat, lesser spend on preventative healthcare for cats and reduced opportunities for research funding for these animals. The dog and cat have substantially similar immune system components, but differences in immune function might in part account for the markedly distinct prevalence and clinicopathological appearance of autoimmune, allergic, idiopathic inflammatory, immunodeficiency, neoplastic and infectious diseases in the two species. Cats have greater genetic diversity than dogs with much lower linkage disequilibrium in feline compared with canine breed groups. Immune function is intrinsically related to the nature of the intestinal microbiome and subtle differences between the canine and feline microbial populations might also impact on immune function and disease resistance. The reasons for the apparent lesser susceptibility of cats to arthropod-borne infectious diseases are likely to be complex, but warrant further investigation.",2016 Sep 20,"Day, Michael J.",Parasit Vectors,,,True
9574215db9b33b5a09628c58401bb06f0433e5c8,PMC,Changes in serum proteins after endotoxin administration in healthy and choline-treated calves,http://dx.doi.org/10.1186/s12917-016-0837-y,PMC5028968,27646125,CC BY,"BACKGROUND: This study aimed to investigate the possible serum protein changes after endotoxin administration in healthy and choline-treated calves using proteomics. These results are expected to contribute to the understanding of the pathophysiological mechanisms of endotoxemia and the beneficial effect of choline administration in this clinical situation. METHODS: Healthy-calves (n = 20) were divided into 4 groups: Control, Choline treated (C), Lipopolysaccharide administered (LPS), and LPS + C. Control calves received 0.9 % NaCl injection. Calves in C and LPS + C groups received choline chloride (1 mg/kg/iv). Endotoxin (LPS) was injected (2 μg/kg/iv) to the calves in LPS and LPS + C groups. Serum samples were collected before and after the treatments. Differentially expressed proteins (> 1.5 fold-change relative to controls) were identified by LC-MS/MS. RESULTS: After LPS administration, 14 proteins increased, and 13 proteins decreased within 48 h as compared to controls. In the LPS group, there were significant increases in serum levels of ragulator complex protein (189-fold) and galectin-3-binding protein (10-fold), but transcription factor MafF and corticosteroid binding globulin were down regulated (≥ 5 fold). As compared with the LPS group, in LPS + C group, fibrinogen gamma-B-chain and antithrombin were up-regulated, while hemopexin and histone H4 were down-regulated. Choline treatment attenuated actin alpha cardiac muscle-1 overexpression after LPS. CONCLUSIONS: LPS administration produces changes in serum proteins associated with lipid metabolism, immune and inflammatory response, protein binding/transport, cell adhesion, venous thrombosis, cardiac contractility and blood coagulation. The administration of choline is associated with changes in proteins which can be related with its beneficial effect in this clinical situation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0837-y) contains supplementary material, which is available to authorized users.",2016 Sep 20,"['Yilmaz, Z.', 'Eralp Inan, O.', 'Kocaturk, M.', 'Baykal, A. T.', 'Hacariz, O.', 'Hatipoglu, I.', 'Tvarijonaviciute, A.', 'Cansev, M.', 'Ceron, J.', 'Ulus, I. H.']",BMC Vet Res,,,True
37f723594fc45504f7f8d4fc7ca0190513a639c0,PMC,Expansion and Functional Divergence of AP2 Group Genes in Spermatophytes Determined by Molecular Evolution and Arabidopsis Mutant Analysis,http://dx.doi.org/10.3389/fpls.2016.01383,PMC5029118,27703459,CC BY,"The APETALA2 (AP2) genes represent the AP2 group within a large group of DNA-binding proteins called AP2/EREBP. The AP2 gene is functional and necessary for flower development, stem cell maintenance, and seed development, whereas the other members of AP2 group redundantly affect flowering time. Here we study the phylogeny of AP2 group genes in spermatophytes. Spermatophyte AP2 group genes can be classified into AP2 and TOE types, six clades, and we found that the AP2 group homologs in gymnosperms belong to the AP2 type, whereas TOE types are absent, which indicates the AP2 type gene are more ancient and TOE type was split out of AP2 type and losing the major function. In Brassicaceae, the expansion of AP2 and TOE type lead to the gene number of AP2 group were up to six. Purifying selection appears to have been the primary driving force of spermatophyte AP2 group evolution, although positive selection occurred in the AP2 clade. The transition from exon to intron of AtAP2 in Arabidopsis mutant leads to the loss of gene function and the same situation was found in AtTOE2. Combining this evolutionary analysis and published research, the results suggest that typical AP2 group genes may first appear in gymnosperms and diverged in angiosperms, following expansion of group members and functional differentiation. In angiosperms, AP2 genes (AP2 clade) inherited key functions from ancestors and other genes of AP2 group lost most function but just remained flowering time controlling in gene formation. In this study, the phylogenies of AP2 group genes in spermatophytes was analyzed, which supported the evidence for the research of gene functional evolution of AP2 group.",2016 Sep 20,"['Wang, Pengkai', 'Cheng, Tielong', 'Lu, Mengzhu', 'Liu, Guangxin', 'Li, Meiping', 'Shi, Jisen', 'Lu, Ye', 'Laux, Thomas', 'Chen, Jinhui']",Front Plant Sci,,,True
376ac2d5c7446918fdc12ef89696687b8a2b23d8,PMC,Differential Regulation of Self-reactive CD4(+) T Cells in Cervical Lymph Nodes and Central Nervous System during Viral Encephalomyelitis,http://dx.doi.org/10.3389/fimmu.2016.00370,PMC5030268,27708643,CC BY,"Viral infections have long been implicated as triggers of autoimmune diseases, including multiple sclerosis (MS), a central nervous system (CNS) inflammatory demyelinating disorder. Epitope spreading, molecular mimicry, cryptic antigen, and bystander activation have been implicated as mechanisms responsible for activating self-reactive (SR) immune cells, ultimately leading to organ-specific autoimmune disease. Taking advantage of coronavirus JHM strain of mouse hepatitis virus (JHMV)-induced demyelination, this study demonstrates that the host also mounts counteractive measures to specifically limit expansion of endogenous SR T cells. In this model, immune-mediated demyelination is associated with induction of SR T cells after viral control. However, their decline during persisting infection, despite ongoing demyelination, suggests an active control mechanism. Antigen-specific IL-10-secreting CD4(+) T cells (Tr1) and Foxp3(+) regulatory T cells (Tregs), both known to control autoimmunity and induced following JHMV infection, were assessed for their relative in vivo suppressive function of SR T cells. Ablation of Foxp3(+) Tregs in chronically infected DEREG mice significantly increased SR CD4(+) T cells within cervical lymph nodes (CLN), albeit without affecting their numbers or activation within the CNS compared to controls. In contrast, infected IL-27 receptor deficient (IL-27R(−/−)) mice, characterized by a drastic reduction of Tr1 cells, revealed that SR CD4(+) T cells in CLN remained unchanged but were specifically increased within the CNS. These results suggest that distinct Treg subsets limit SR T cells in the draining lymph nodes and CNS to maximize suppression of SR T-cell-mediated autoimmune pathology. The JHMV model is thus valuable to decipher tissue-specific mechanisms preventing autoimmunity.",2016 Sep 21,"['Savarin, Carine', 'Bergmann, Cornelia C.', 'Hinton, David R.', 'Stohlman, Stephen A.']",Front Immunol,,,True
69d3400351b1b4dbce54ecdec3d4c897dc76b9a8,PMC,Tuberculosis Susceptibility and Vaccine Protection Are Independently Controlled by Host Genotype,http://dx.doi.org/10.1128/mBio.01516-16,PMC5030360,27651361,CC BY,"The outcome of Mycobacterium tuberculosis infection and the immunological response to the bacillus Calmette-Guerin (BCG) vaccine are highly variable in humans. Deciphering the relative importance of host genetics, environment, and vaccine preparation for the efficacy of BCG has proven difficult in natural populations. We developed a model system that captures the breadth of immunological responses observed in outbred individual mice, which can be used to understand the contribution of host genetics to vaccine efficacy. This system employs a panel of highly diverse inbred mouse strains, consisting of the founders and recombinant progeny of the “Collaborative Cross” project. Unlike natural populations, the structure of this panel allows the serial evaluation of genetically identical individuals and the quantification of genotype-specific effects of interventions such as vaccination. When analyzed in the aggregate, our panel resembled natural populations in several important respects: the animals displayed a broad range of susceptibility to M. tuberculosis, differed in their immunological responses to infection, and were not durably protected by BCG vaccination. However, when analyzed at the genotype level, we found that these phenotypic differences were heritable. M. tuberculosis susceptibility varied between lines, from extreme sensitivity to progressive M. tuberculosis clearance. Similarly, only a minority of the genotypes was protected by vaccination. The efficacy of BCG was genetically separable from susceptibility to M. tuberculosis, and the lack of efficacy in the aggregate analysis was driven by nonresponsive lines that mounted a qualitatively distinct response to infection. These observations support an important role for host genetic diversity in determining BCG efficacy and provide a new resource to rationally develop more broadly efficacious vaccines.",2016 Sep 20,"['Smith, Clare M.', 'Proulx, Megan K.', 'Olive, Andrew J.', 'Laddy, Dominick', 'Mishra, Bibhuti B.', 'Moss, Caitlin', 'Gutierrez, Nuria Martinez', 'Bellerose, Michelle M.', 'Barreira-Silva, Palmira', 'Phuah, Jia Yao', 'Baker, Richard E.', 'Behar, Samuel M.', 'Kornfeld, Hardy', 'Evans, Thomas G.', 'Beamer, Gillian', 'Sassetti, Christopher M.']",mBio,,,True
044e273c24dbb1ec49d20e760568a100efffab20,PMC,Tuberculosis Susceptibility and Vaccine Protection Are Independently Controlled by Host Genotype,http://dx.doi.org/10.1128/mBio.01516-16,PMC5030360,27651361,CC BY,"The outcome of Mycobacterium tuberculosis infection and the immunological response to the bacillus Calmette-Guerin (BCG) vaccine are highly variable in humans. Deciphering the relative importance of host genetics, environment, and vaccine preparation for the efficacy of BCG has proven difficult in natural populations. We developed a model system that captures the breadth of immunological responses observed in outbred individual mice, which can be used to understand the contribution of host genetics to vaccine efficacy. This system employs a panel of highly diverse inbred mouse strains, consisting of the founders and recombinant progeny of the “Collaborative Cross” project. Unlike natural populations, the structure of this panel allows the serial evaluation of genetically identical individuals and the quantification of genotype-specific effects of interventions such as vaccination. When analyzed in the aggregate, our panel resembled natural populations in several important respects: the animals displayed a broad range of susceptibility to M. tuberculosis, differed in their immunological responses to infection, and were not durably protected by BCG vaccination. However, when analyzed at the genotype level, we found that these phenotypic differences were heritable. M. tuberculosis susceptibility varied between lines, from extreme sensitivity to progressive M. tuberculosis clearance. Similarly, only a minority of the genotypes was protected by vaccination. The efficacy of BCG was genetically separable from susceptibility to M. tuberculosis, and the lack of efficacy in the aggregate analysis was driven by nonresponsive lines that mounted a qualitatively distinct response to infection. These observations support an important role for host genetic diversity in determining BCG efficacy and provide a new resource to rationally develop more broadly efficacious vaccines.",2016 Sep 20,"['Smith, Clare M.', 'Proulx, Megan K.', 'Olive, Andrew J.', 'Laddy, Dominick', 'Mishra, Bibhuti B.', 'Moss, Caitlin', 'Gutierrez, Nuria Martinez', 'Bellerose, Michelle M.', 'Barreira-Silva, Palmira', 'Phuah, Jia Yao', 'Baker, Richard E.', 'Behar, Samuel M.', 'Kornfeld, Hardy', 'Evans, Thomas G.', 'Beamer, Gillian', 'Sassetti, Christopher M.']",mBio,,,False
a2f961fd82a92373256efd31318904eaa6cf6c64,PMC,Prediction and In Silico Identification of Novel B-Cells and T-Cells Epitopes in the S1-Spike Glycoprotein of M41 and CR88 (793/B) Infectious Bronchitis Virus Serotypes for Application in Peptide Vaccines,http://dx.doi.org/10.1155/2016/5484972,PMC5030393,27667997,CC BY,"Bioinformatic analysis was used to predict antigenic B-cell and T-cell epitopes within the S1 glycoprotein of M41 and CR88 IBV strains. A conserved linear B-cell epitope peptide, YTSNETTDVTS(175–185), was identified in M41 IBV strains while three such epitopes types namely, VSNASPNSGGVD(279–290), HPKCNFRPENI(328–338), and NETNNAGSVSDCTAGT(54–69), were predicted in CR88 IBV strains. Analysis of MHCI binding peptides in M41 IBV strains revealed the presence of 15 antigenic peptides out of which 12 were highly conserved in 96–100% of the total M41 strains analysed. Interestingly three of these peptides, GGPITYKVM(208), WFNSLSVSI(356), and YLADAGLAI(472), relatively had high antigenicity index (>1.0). On the other hand, 11 MHCI binding epitope peptides were identified in CR88 IBV strains. Of these, five peptides were found to be highly conserved with a range between 90% and 97%. However, WFNSLSVSL(358), SYNISAASV(88), and YNISAASVA(89) peptides comparably showed high antigenicity scores (>1.0). Combination of antigenic B-cells and T-cells peptides that are conserved across many strains as approach to evoke humoral and CTL immune response will potentially lead to a broad-based vaccine that could reduce the challenges in using live attenuated vaccine technology in the control of IBV infection in poultry.",2016 Sep 7,"['Bande, Faruku', 'Arshad, Siti Suri', 'Hair Bejo, Mohd', 'Kadkhodaei, Saeid', 'Omar, Abdul Rahman']",Adv Bioinformatics,,,True
f5ff89ebfdd0375d034c112c6c1c7e163fa69a0c,PMC,"Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in Réunion Island, 2011-2012",http://dx.doi.org/10.1371/journal.pone.0163377,PMC5031398,27654509,CC BY,"In Réunion Island, despite an influenza surveillance established since 1996 by the sentinel general practitioner’s network, little is known about the etiology of Influenza like-illness (ILI) that differs from influenza viruses in a tropical area. We set up a retrospective study using nasal swabs collected by sentinel GPs from ILI patients in 2011 and 2012. A total of 250 swabs were randomly selected and analyzed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) including research of 18 viruses and 4 bacteria. We detected respiratory viruses in 169/222 (76.1%) samples, mostly rhinovirus (23.4%), influenza A virus (21.2%), influenza B virus (12.6%), coronavirus (4.9%) and Human metapneumovirus (3.6%). Nine swabs (5.3% of positive swabs) revealed co-infections with two viruses identified, among which six concerned co-infections with influenza viruses. We observed important seasonal differences, with circulation of Human Metapneumoviruses, RSV A and B and coronavirus only during summer; whereas parainfluenza viruses were identified only during winter. In conclusion, this study highlights a substantial circulation of multiple respiratory pathogens in Réunion Island throughout the year. It shows that ILI are not only attributable to influenza and underlines the need for biological surveillance. As the use of multiplex RT-PCR showed its efficacy, it is now used routinely in the surveillance of ILI.",2016 Sep 21,"['Brottet, Elise', 'Jaffar-Bandjee, Marie-Christine', 'Li-Pat-Yuen, Ghislaine', 'Filleul, Laurent']",PLoS One,,,True
b11cf879da2036d92fbdbbca07fd8cb7f0416e5f,PMC,A Rationally Designed TNF-α Epitope-Scaffold Immunogen Induces Sustained Antibody Response and Alleviates Collagen-Induced Arthritis in Mice,http://dx.doi.org/10.1371/journal.pone.0163080,PMC5033357,27658047,CC BY,"The TNF-α biological inhibitors have significantly improved the clinical outcomes of many autoimmune diseases, in particular rheumatoid arthritis. However, the practical uses are limited due to high costs and the risk of anti-drug antibody responses. Attempts to develop anti-TNF-α vaccines have generated encouraging data in animal models, however, data from clinical trials have not met expectations. In present study, we designed a TNF-α epitope-scaffold immunogen DTNF7 using the transmembrane domain of diphtheria toxin, named DTT as a scaffold. Molecular dynamics simulation shows that the grafted TNF-α epitope is entirely surface-exposed and presented in a native-like conformation while the rigid helical structure of DTT is minimally perturbed, thereby rendering the immunogen highly stable. Immunization of mice with alum formulated DTNF7 induced humoral responses against native TNF-α, and the antibody titer was sustained for more than 6 months, which supports a role of the universal CD4 T cell epitopes of DTT in breaking self-immune tolerance. In a mouse model of rheumatoid arthritis, DTNF7-alum vaccination markedly delayed the onset of collagen-induced arthritis, and reduced incidence as well as clinical score. DTT is presumed safe as an epitope carrier because a catalytic inactive mutant of diphtheria toxin, CRM197 has good clinical safety records as an active vaccine component. Taken all together, we show that DTT-based epitope vaccine is a promising strategy for prevention and treatment of autoimmune diseases.",2016 Sep 22,"['Zhang, Li', 'Wang, Jin', 'Xu, Aizhang', 'Zhong, Conghao', 'Lu, Wuguang', 'Deng, Li', 'Li, Rongxiu']",PLoS One,,,True
e96b011c26501fc8432fd96787fe0aba49a08e0b,PMC,Reduced Risk of Importing Ebola Virus Disease because of Travel Restrictions in 2014: A Retrospective Epidemiological Modeling Study,http://dx.doi.org/10.1371/journal.pone.0163418,PMC5033593,27657544,CC BY,"BACKGROUND: An epidemic of Ebola virus disease (EVD) from 2013–16 posed a serious risk of global spread during its early growth phase. A post-epidemic evaluation of the effectiveness of travel restrictions has yet to be conducted. The present study aimed to estimate the effectiveness of travel restrictions in reducing the risk of importation from mid-August to September, 2014, using a simple hazard-based statistical model. METHODOLOGY/PRINCIPAL FINDINGS: The hazard rate was modeled as an inverse function of the effective distance, an excellent predictor of disease spread, which was calculated from the airline transportation network. By analyzing datasets of the date of EVD case importation from the 15(th) of July to the 15(th) of September 2014, and assuming that the network structure changed from the 8(th) of August 2014 because of travel restrictions, parameters that characterized the hazard rate were estimated. The absolute risk reduction and relative risk reductions due to travel restrictions were estimated to be less than 1% and about 20%, respectively, for all models tested. Effectiveness estimates among African countries were greater than those for other countries outside Africa. CONCLUSIONS: The travel restrictions were not effective enough to expect the prevention of global spread of Ebola virus disease. It is more efficient to control the spread of disease locally during an early phase of an epidemic than to attempt to control the epidemic at international borders. Capacity building for local containment and coordinated and expedited international cooperation are essential to reduce the risk of global transmission.",2016 Sep 22,"['Otsuki, Shiori', 'Nishiura, Hiroshi']",PLoS One,,,True
983e9c303f6c0082aa4fad58a82da11a16262a01,PMC,High diversity of picornaviruses in rats from different continents revealed by deep sequencing,http://dx.doi.org/10.1038/emi.2016.90,PMC5034103,27530749,CC BY,"Outbreaks of zoonotic diseases in humans and livestock are not uncommon, and an important component in containment of such emerging viral diseases is rapid and reliable diagnostics. Such methods are often PCR-based and hence require the availability of sequence data from the pathogen. Rattus norvegicus (R. norvegicus) is a known reservoir for important zoonotic pathogens. Transmission may be direct via contact with the animal, for example, through exposure to its faecal matter, or indirectly mediated by arthropod vectors. Here we investigated the viral content in rat faecal matter (n=29) collected from two continents by analyzing 2.2 billion next-generation sequencing reads derived from both DNA and RNA. Among other virus families, we found sequences from members of the Picornaviridae to be abundant in the microbiome of all the samples. Here we describe the diversity of the picornavirus-like contigs including near-full-length genomes closely related to the Boone cardiovirus and Theiler's encephalomyelitis virus. From this study, we conclude that picornaviruses within R. norvegicus are more diverse than previously recognized. The virome of R. norvegicus should be investigated further to assess the full potential for zoonotic virus transmission.",2016 Aug 17,"['Hansen, Thomas Arn', 'Mollerup, Sarah', 'Nguyen, Nam-phuong', 'White, Nicole E', 'Coghlan, Megan', 'Alquezar-Planas, David E', 'Joshi, Tejal', 'Jensen, Randi Holm', 'Fridholm, Helena', 'Kjartansdóttir, Kristín Rós', 'Mourier, Tobias', 'Warnow, Tandy', 'Belsham, Graham J', 'Bunce, Michael', 'Willerslev, Eske', 'Nielsen, Lars Peter', 'Vinner, Lasse', 'Hansen, Anders Johannes']",Emerg Microbes Infect,,,True
2e4ddad3f80f7e1cdad82f054190c0656b1e22a4,PMC,High diversity of picornaviruses in rats from different continents revealed by deep sequencing,http://dx.doi.org/10.1038/emi.2016.90,PMC5034103,27530749,CC BY,"Outbreaks of zoonotic diseases in humans and livestock are not uncommon, and an important component in containment of such emerging viral diseases is rapid and reliable diagnostics. Such methods are often PCR-based and hence require the availability of sequence data from the pathogen. Rattus norvegicus (R. norvegicus) is a known reservoir for important zoonotic pathogens. Transmission may be direct via contact with the animal, for example, through exposure to its faecal matter, or indirectly mediated by arthropod vectors. Here we investigated the viral content in rat faecal matter (n=29) collected from two continents by analyzing 2.2 billion next-generation sequencing reads derived from both DNA and RNA. Among other virus families, we found sequences from members of the Picornaviridae to be abundant in the microbiome of all the samples. Here we describe the diversity of the picornavirus-like contigs including near-full-length genomes closely related to the Boone cardiovirus and Theiler's encephalomyelitis virus. From this study, we conclude that picornaviruses within R. norvegicus are more diverse than previously recognized. The virome of R. norvegicus should be investigated further to assess the full potential for zoonotic virus transmission.",2016 Aug 17,"['Hansen, Thomas Arn', 'Mollerup, Sarah', 'Nguyen, Nam-phuong', 'White, Nicole E', 'Coghlan, Megan', 'Alquezar-Planas, David E', 'Joshi, Tejal', 'Jensen, Randi Holm', 'Fridholm, Helena', 'Kjartansdóttir, Kristín Rós', 'Mourier, Tobias', 'Warnow, Tandy', 'Belsham, Graham J', 'Bunce, Michael', 'Willerslev, Eske', 'Nielsen, Lars Peter', 'Vinner, Lasse', 'Hansen, Anders Johannes']",Emerg Microbes Infect,,,False
3231d73e559bb36891c0740d05c33549d4d5ad16,PMC,High diversity of picornaviruses in rats from different continents revealed by deep sequencing,http://dx.doi.org/10.1038/emi.2016.90,PMC5034103,27530749,CC BY,"Outbreaks of zoonotic diseases in humans and livestock are not uncommon, and an important component in containment of such emerging viral diseases is rapid and reliable diagnostics. Such methods are often PCR-based and hence require the availability of sequence data from the pathogen. Rattus norvegicus (R. norvegicus) is a known reservoir for important zoonotic pathogens. Transmission may be direct via contact with the animal, for example, through exposure to its faecal matter, or indirectly mediated by arthropod vectors. Here we investigated the viral content in rat faecal matter (n=29) collected from two continents by analyzing 2.2 billion next-generation sequencing reads derived from both DNA and RNA. Among other virus families, we found sequences from members of the Picornaviridae to be abundant in the microbiome of all the samples. Here we describe the diversity of the picornavirus-like contigs including near-full-length genomes closely related to the Boone cardiovirus and Theiler's encephalomyelitis virus. From this study, we conclude that picornaviruses within R. norvegicus are more diverse than previously recognized. The virome of R. norvegicus should be investigated further to assess the full potential for zoonotic virus transmission.",2016 Aug 17,"['Hansen, Thomas Arn', 'Mollerup, Sarah', 'Nguyen, Nam-phuong', 'White, Nicole E', 'Coghlan, Megan', 'Alquezar-Planas, David E', 'Joshi, Tejal', 'Jensen, Randi Holm', 'Fridholm, Helena', 'Kjartansdóttir, Kristín Rós', 'Mourier, Tobias', 'Warnow, Tandy', 'Belsham, Graham J', 'Bunce, Michael', 'Willerslev, Eske', 'Nielsen, Lars Peter', 'Vinner, Lasse', 'Hansen, Anders Johannes']",Emerg Microbes Infect,,,False
68fa5fdbeaeb3e7ff1859b3355c4c639a5784259,PMC,High diversity of picornaviruses in rats from different continents revealed by deep sequencing,http://dx.doi.org/10.1038/emi.2016.90,PMC5034103,27530749,CC BY,"Outbreaks of zoonotic diseases in humans and livestock are not uncommon, and an important component in containment of such emerging viral diseases is rapid and reliable diagnostics. Such methods are often PCR-based and hence require the availability of sequence data from the pathogen. Rattus norvegicus (R. norvegicus) is a known reservoir for important zoonotic pathogens. Transmission may be direct via contact with the animal, for example, through exposure to its faecal matter, or indirectly mediated by arthropod vectors. Here we investigated the viral content in rat faecal matter (n=29) collected from two continents by analyzing 2.2 billion next-generation sequencing reads derived from both DNA and RNA. Among other virus families, we found sequences from members of the Picornaviridae to be abundant in the microbiome of all the samples. Here we describe the diversity of the picornavirus-like contigs including near-full-length genomes closely related to the Boone cardiovirus and Theiler's encephalomyelitis virus. From this study, we conclude that picornaviruses within R. norvegicus are more diverse than previously recognized. The virome of R. norvegicus should be investigated further to assess the full potential for zoonotic virus transmission.",2016 Aug 17,"['Hansen, Thomas Arn', 'Mollerup, Sarah', 'Nguyen, Nam-phuong', 'White, Nicole E', 'Coghlan, Megan', 'Alquezar-Planas, David E', 'Joshi, Tejal', 'Jensen, Randi Holm', 'Fridholm, Helena', 'Kjartansdóttir, Kristín Rós', 'Mourier, Tobias', 'Warnow, Tandy', 'Belsham, Graham J', 'Bunce, Michael', 'Willerslev, Eske', 'Nielsen, Lars Peter', 'Vinner, Lasse', 'Hansen, Anders Johannes']",Emerg Microbes Infect,,,False
ba25ee1675af879a4885ee4e2cf10fe91ef6fa04,PMC,High diversity of picornaviruses in rats from different continents revealed by deep sequencing,http://dx.doi.org/10.1038/emi.2016.90,PMC5034103,27530749,CC BY,"Outbreaks of zoonotic diseases in humans and livestock are not uncommon, and an important component in containment of such emerging viral diseases is rapid and reliable diagnostics. Such methods are often PCR-based and hence require the availability of sequence data from the pathogen. Rattus norvegicus (R. norvegicus) is a known reservoir for important zoonotic pathogens. Transmission may be direct via contact with the animal, for example, through exposure to its faecal matter, or indirectly mediated by arthropod vectors. Here we investigated the viral content in rat faecal matter (n=29) collected from two continents by analyzing 2.2 billion next-generation sequencing reads derived from both DNA and RNA. Among other virus families, we found sequences from members of the Picornaviridae to be abundant in the microbiome of all the samples. Here we describe the diversity of the picornavirus-like contigs including near-full-length genomes closely related to the Boone cardiovirus and Theiler's encephalomyelitis virus. From this study, we conclude that picornaviruses within R. norvegicus are more diverse than previously recognized. The virome of R. norvegicus should be investigated further to assess the full potential for zoonotic virus transmission.",2016 Aug 17,"['Hansen, Thomas Arn', 'Mollerup, Sarah', 'Nguyen, Nam-phuong', 'White, Nicole E', 'Coghlan, Megan', 'Alquezar-Planas, David E', 'Joshi, Tejal', 'Jensen, Randi Holm', 'Fridholm, Helena', 'Kjartansdóttir, Kristín Rós', 'Mourier, Tobias', 'Warnow, Tandy', 'Belsham, Graham J', 'Bunce, Michael', 'Willerslev, Eske', 'Nielsen, Lars Peter', 'Vinner, Lasse', 'Hansen, Anders Johannes']",Emerg Microbes Infect,,,False
09affbdb095d902261d09f42aea0c24b932e6f84,PMC,High diversity of picornaviruses in rats from different continents revealed by deep sequencing,http://dx.doi.org/10.1038/emi.2016.90,PMC5034103,27530749,CC BY,"Outbreaks of zoonotic diseases in humans and livestock are not uncommon, and an important component in containment of such emerging viral diseases is rapid and reliable diagnostics. Such methods are often PCR-based and hence require the availability of sequence data from the pathogen. Rattus norvegicus (R. norvegicus) is a known reservoir for important zoonotic pathogens. Transmission may be direct via contact with the animal, for example, through exposure to its faecal matter, or indirectly mediated by arthropod vectors. Here we investigated the viral content in rat faecal matter (n=29) collected from two continents by analyzing 2.2 billion next-generation sequencing reads derived from both DNA and RNA. Among other virus families, we found sequences from members of the Picornaviridae to be abundant in the microbiome of all the samples. Here we describe the diversity of the picornavirus-like contigs including near-full-length genomes closely related to the Boone cardiovirus and Theiler's encephalomyelitis virus. From this study, we conclude that picornaviruses within R. norvegicus are more diverse than previously recognized. The virome of R. norvegicus should be investigated further to assess the full potential for zoonotic virus transmission.",2016 Aug 17,"['Hansen, Thomas Arn', 'Mollerup, Sarah', 'Nguyen, Nam-phuong', 'White, Nicole E', 'Coghlan, Megan', 'Alquezar-Planas, David E', 'Joshi, Tejal', 'Jensen, Randi Holm', 'Fridholm, Helena', 'Kjartansdóttir, Kristín Rós', 'Mourier, Tobias', 'Warnow, Tandy', 'Belsham, Graham J', 'Bunce, Michael', 'Willerslev, Eske', 'Nielsen, Lars Peter', 'Vinner, Lasse', 'Hansen, Anders Johannes']",Emerg Microbes Infect,,,False
f0fd369a572627c9df84aa15af3932f2de39f7fc,PMC,High diversity of picornaviruses in rats from different continents revealed by deep sequencing,http://dx.doi.org/10.1038/emi.2016.90,PMC5034103,27530749,CC BY,"Outbreaks of zoonotic diseases in humans and livestock are not uncommon, and an important component in containment of such emerging viral diseases is rapid and reliable diagnostics. Such methods are often PCR-based and hence require the availability of sequence data from the pathogen. Rattus norvegicus (R. norvegicus) is a known reservoir for important zoonotic pathogens. Transmission may be direct via contact with the animal, for example, through exposure to its faecal matter, or indirectly mediated by arthropod vectors. Here we investigated the viral content in rat faecal matter (n=29) collected from two continents by analyzing 2.2 billion next-generation sequencing reads derived from both DNA and RNA. Among other virus families, we found sequences from members of the Picornaviridae to be abundant in the microbiome of all the samples. Here we describe the diversity of the picornavirus-like contigs including near-full-length genomes closely related to the Boone cardiovirus and Theiler's encephalomyelitis virus. From this study, we conclude that picornaviruses within R. norvegicus are more diverse than previously recognized. The virome of R. norvegicus should be investigated further to assess the full potential for zoonotic virus transmission.",2016 Aug 17,"['Hansen, Thomas Arn', 'Mollerup, Sarah', 'Nguyen, Nam-phuong', 'White, Nicole E', 'Coghlan, Megan', 'Alquezar-Planas, David E', 'Joshi, Tejal', 'Jensen, Randi Holm', 'Fridholm, Helena', 'Kjartansdóttir, Kristín Rós', 'Mourier, Tobias', 'Warnow, Tandy', 'Belsham, Graham J', 'Bunce, Michael', 'Willerslev, Eske', 'Nielsen, Lars Peter', 'Vinner, Lasse', 'Hansen, Anders Johannes']",Emerg Microbes Infect,,,False
fd23dc1e8db2de0724d76fdadf0fd2f675be960e,PMC,Converting monoclonal antibody-based immunotherapies from passive to active: bringing immune complexes into play,http://dx.doi.org/10.1038/emi.2016.97,PMC5034104,27530750,CC BY,"Monoclonal antibodies (mAbs), which currently constitute the main class of biotherapeutics, are now recognized as major medical tools that are increasingly being considered to fight severe viral infections. Indeed, the number of antiviral mAbs developed in recent years has grown exponentially. Although their direct effects on viral blunting have been studied in detail, their potential immunomodulatory actions have been overlooked until recently. The ability of antiviral mAbs to modulate antiviral immune responses in infected organisms has recently been revealed. More specifically, upon recognition of their cognate antigens, mAbs form immune complexes (ICs) that can be recognized by the Fc receptors expressed on different immune cells of infected individuals. This binding may be followed by the modulation of the host immune responses. Harnessing this immunomodulatory property may facilitate improvements in the therapeutic potential of antiviral mAbs. This review focuses on the role of ICs formed with different viral determinants and mAbs in the induction of antiviral immune responses in the context of both passive immunotherapies and vaccination strategies. Potential deleterious effects of ICs on the host immune response are also discussed.",2016 Aug 17,"['Lambour, Jennifer', 'Naranjo-Gomez, Mar', 'Piechaczyk, Marc', 'Pelegrin, Mireia']",Emerg Microbes Infect,,,True
e44632c9b598cac15ccda521e13c65ca9fcf7426,PMC,The Healthy Infant Nasal Transcriptome: A Benchmark Study,http://dx.doi.org/10.1038/srep33994,PMC5034274,27658638,CC BY,"Responses by resident cells are likely to play a key role in determining the severity of respiratory disease. However, sampling of the airways poses a significant challenge, particularly in infants and children. Here, we report a reliable method for obtaining nasal epithelial cell RNA from infants for genome-wide transcriptomic analysis, and describe baseline expression characteristics in an asymptomatic cohort. Nasal epithelial cells were collected by brushing of the inferior turbinates, and gene expression was interrogated by RNA-seq analysis. Reliable recovery of RNA occurred in the absence of adverse events. We observed high expression of epithelial cell markers and similarity to the transcriptome for intrapulmonary airway epithelial cells. We identified genes displaying low and high expression variability, both inherently, and in response to environmental exposures. The greatest gene expression differences in this asymptomatic cohort were associated with the presence of known pathogenic viruses and/or bacteria. Robust bacteria-associated gene expression patterns were significantly associated with the presence of Moraxella. In summary, we have developed a reliable method for interrogating the infant airway transcriptome by sampling the nasal epithelium. Our data demonstrates both the fidelity and feasibility of our methodology, and describes normal gene expression and variation within a healthy infant cohort.",2016 Sep 23,"['Chu, Chin-Yi', 'Qiu, Xing', 'Wang, Lu', 'Bhattacharya, Soumyaroop', 'Lofthus, Gerry', 'Corbett, Anthony', 'Holden-Wiltse, Jeanne', 'Grier, Alex', 'Tesini, Brenda', 'Gill, Steven R.', 'Falsey, Ann R.', 'Caserta, Mary T.', 'Walsh, Edward E.', 'Mariani, Thomas J.']",Sci Rep,,,True
669511bfee375dd73d141c494f53d027c903f734,PMC,The Healthy Infant Nasal Transcriptome: A Benchmark Study,http://dx.doi.org/10.1038/srep33994,PMC5034274,27658638,CC BY,"Responses by resident cells are likely to play a key role in determining the severity of respiratory disease. However, sampling of the airways poses a significant challenge, particularly in infants and children. Here, we report a reliable method for obtaining nasal epithelial cell RNA from infants for genome-wide transcriptomic analysis, and describe baseline expression characteristics in an asymptomatic cohort. Nasal epithelial cells were collected by brushing of the inferior turbinates, and gene expression was interrogated by RNA-seq analysis. Reliable recovery of RNA occurred in the absence of adverse events. We observed high expression of epithelial cell markers and similarity to the transcriptome for intrapulmonary airway epithelial cells. We identified genes displaying low and high expression variability, both inherently, and in response to environmental exposures. The greatest gene expression differences in this asymptomatic cohort were associated with the presence of known pathogenic viruses and/or bacteria. Robust bacteria-associated gene expression patterns were significantly associated with the presence of Moraxella. In summary, we have developed a reliable method for interrogating the infant airway transcriptome by sampling the nasal epithelium. Our data demonstrates both the fidelity and feasibility of our methodology, and describes normal gene expression and variation within a healthy infant cohort.",2016 Sep 23,"['Chu, Chin-Yi', 'Qiu, Xing', 'Wang, Lu', 'Bhattacharya, Soumyaroop', 'Lofthus, Gerry', 'Corbett, Anthony', 'Holden-Wiltse, Jeanne', 'Grier, Alex', 'Tesini, Brenda', 'Gill, Steven R.', 'Falsey, Ann R.', 'Caserta, Mary T.', 'Walsh, Edward E.', 'Mariani, Thomas J.']",Sci Rep,,,True
d75d565a2c7f9bc13b6dbb4fa45eb85e2a1c72cd,PMC,Model-Informed Risk Assessment and Decision Making for an Emerging Infectious Disease in the Asia-Pacific Region,http://dx.doi.org/10.1371/journal.pntd.0005018,PMC5035030,27661978,CC BY,"BACKGROUND: Effective response to emerging infectious disease (EID) threats relies on health care systems that can detect and contain localised outbreaks before they reach a national or international scale. The Asia-Pacific region contains low and middle income countries in which the risk of EID outbreaks is elevated and whose health care systems may require international support to effectively detect and respond to such events. The absence of comprehensive data on populations, health care systems and disease characteristics in this region makes risk assessment and decisions about the provision of such support challenging. METHODOLOGY/PRINCIPAL FINDINGS: We describe a mathematical modelling framework that can inform this process by integrating available data sources, systematically explore the effects of uncertainty, and provide estimates of outbreak risk under a range of intervention scenarios. We illustrate the use of this framework in the context of a potential importation of Ebola Virus Disease into the Asia-Pacific region. Results suggest that, across a wide range of plausible scenarios, preemptive interventions supporting the timely detection of early cases provide substantially greater reductions in the probability of large outbreaks than interventions that support health care system capacity after an outbreak has commenced. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates how, in the presence of substantial uncertainty about health care system infrastructure and other relevant aspects of disease control, mathematical models can be used to assess the constraints that limited resources place upon the ability of local health care systems to detect and respond to EID outbreaks in a timely and effective fashion. Our framework can help evaluate the relative impact of these constraints to identify resourcing priorities for health care system support, in order to inform principled and quantifiable decision making.",2016 Sep 23,"['Moss, Robert', 'Hickson, Roslyn I.', 'McVernon, Jodie', 'McCaw, James M.', 'Hort, Krishna', 'Black, Jim', 'Madden, John R.', 'Tran, Nhi H.', 'McBryde, Emma S.', 'Geard, Nicholas']",PLoS Negl Trop Dis,,,True
f0dbc87d51c4d8a07ff83c5fc53afac5f973a20a,PMC,Model-Informed Risk Assessment and Decision Making for an Emerging Infectious Disease in the Asia-Pacific Region,http://dx.doi.org/10.1371/journal.pntd.0005018,PMC5035030,27661978,CC BY,"BACKGROUND: Effective response to emerging infectious disease (EID) threats relies on health care systems that can detect and contain localised outbreaks before they reach a national or international scale. The Asia-Pacific region contains low and middle income countries in which the risk of EID outbreaks is elevated and whose health care systems may require international support to effectively detect and respond to such events. The absence of comprehensive data on populations, health care systems and disease characteristics in this region makes risk assessment and decisions about the provision of such support challenging. METHODOLOGY/PRINCIPAL FINDINGS: We describe a mathematical modelling framework that can inform this process by integrating available data sources, systematically explore the effects of uncertainty, and provide estimates of outbreak risk under a range of intervention scenarios. We illustrate the use of this framework in the context of a potential importation of Ebola Virus Disease into the Asia-Pacific region. Results suggest that, across a wide range of plausible scenarios, preemptive interventions supporting the timely detection of early cases provide substantially greater reductions in the probability of large outbreaks than interventions that support health care system capacity after an outbreak has commenced. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates how, in the presence of substantial uncertainty about health care system infrastructure and other relevant aspects of disease control, mathematical models can be used to assess the constraints that limited resources place upon the ability of local health care systems to detect and respond to EID outbreaks in a timely and effective fashion. Our framework can help evaluate the relative impact of these constraints to identify resourcing priorities for health care system support, in order to inform principled and quantifiable decision making.",2016 Sep 23,"['Moss, Robert', 'Hickson, Roslyn I.', 'McVernon, Jodie', 'McCaw, James M.', 'Hort, Krishna', 'Black, Jim', 'Madden, John R.', 'Tran, Nhi H.', 'McBryde, Emma S.', 'Geard, Nicholas']",PLoS Negl Trop Dis,,,True
42e321eedba25d380ae44d16cdf0bbdeab83d665,PMC,Divergent Sapovirus Strains and Infection Prevalence in Wild Carnivores in the Serengeti Ecosystem: A Long-Term Study,http://dx.doi.org/10.1371/journal.pone.0163548,PMC5035092,27661997,CC BY,"The genus Sapovirus, in the family Caliciviridae, includes enteric viruses of humans and domestic animals. Information on sapovirus infection of wildlife is limited and is currently lacking for any free-ranging wildlife species in Africa. By screening a large number of predominantly fecal samples (n = 631) obtained from five carnivore species in the Serengeti ecosystem, East Africa, sapovirus RNA was detected in the spotted hyena (Crocuta crocuta, family Hyaenidae), African lion (Panthera leo, family Felidae), and bat-eared fox (Otocyon megalotis, family Canidae), but not in golden or silver-backed jackals (Canis aureus and C. mesomelas, respectively, family Canidae). A phylogenetic analysis based on partial RNA-dependent RNA polymerase (RdRp) gene sequences placed the sapovirus strains from African carnivores in a monophyletic group. Within this monophyletic group, sapovirus strains from spotted hyenas formed one independent sub-group, and those from bat-eared fox and African lion a second sub-group. The percentage nucleotide similarity between sapoviruses from African carnivores and those from other species was low (< 70.4%). Long-term monitoring of sapovirus in a population of individually known spotted hyenas from 2001 to 2012 revealed: i) a relatively high overall infection prevalence (34.8%); ii) the circulation of several genetically diverse variants; iii) large fluctuations in infection prevalence across years, indicative of outbreaks; iv) no significant difference in the likelihood of infection between animals in different age categories. The likelihood of sapovirus infection decreased with increasing hyena group size, suggesting an encounter reduction effect, but was independent of socially mediated ano-genital contact, or the extent of the area over which an individual roamed.",2016 Sep 23,"['Olarte-Castillo, Ximena A.', 'Hofer, Heribert', 'Goller, Katja V.', 'Martella, Vito', 'Moehlman, Patricia D.', 'East, Marion L.']",PLoS One,,,True
8a77d1db3e7b6eb0cecfc42f737e4a437ea5f720,PMC,Divergent Sapovirus Strains and Infection Prevalence in Wild Carnivores in the Serengeti Ecosystem: A Long-Term Study,http://dx.doi.org/10.1371/journal.pone.0163548,PMC5035092,27661997,CC BY,"The genus Sapovirus, in the family Caliciviridae, includes enteric viruses of humans and domestic animals. Information on sapovirus infection of wildlife is limited and is currently lacking for any free-ranging wildlife species in Africa. By screening a large number of predominantly fecal samples (n = 631) obtained from five carnivore species in the Serengeti ecosystem, East Africa, sapovirus RNA was detected in the spotted hyena (Crocuta crocuta, family Hyaenidae), African lion (Panthera leo, family Felidae), and bat-eared fox (Otocyon megalotis, family Canidae), but not in golden or silver-backed jackals (Canis aureus and C. mesomelas, respectively, family Canidae). A phylogenetic analysis based on partial RNA-dependent RNA polymerase (RdRp) gene sequences placed the sapovirus strains from African carnivores in a monophyletic group. Within this monophyletic group, sapovirus strains from spotted hyenas formed one independent sub-group, and those from bat-eared fox and African lion a second sub-group. The percentage nucleotide similarity between sapoviruses from African carnivores and those from other species was low (< 70.4%). Long-term monitoring of sapovirus in a population of individually known spotted hyenas from 2001 to 2012 revealed: i) a relatively high overall infection prevalence (34.8%); ii) the circulation of several genetically diverse variants; iii) large fluctuations in infection prevalence across years, indicative of outbreaks; iv) no significant difference in the likelihood of infection between animals in different age categories. The likelihood of sapovirus infection decreased with increasing hyena group size, suggesting an encounter reduction effect, but was independent of socially mediated ano-genital contact, or the extent of the area over which an individual roamed.",2016 Sep 23,"['Olarte-Castillo, Ximena A.', 'Hofer, Heribert', 'Goller, Katja V.', 'Martella, Vito', 'Moehlman, Patricia D.', 'East, Marion L.']",PLoS One,,,False
8b544e8b7379e0e8f684ecba104f168adea0c9ce,PMC,Divergent Sapovirus Strains and Infection Prevalence in Wild Carnivores in the Serengeti Ecosystem: A Long-Term Study,http://dx.doi.org/10.1371/journal.pone.0163548,PMC5035092,27661997,CC BY,"The genus Sapovirus, in the family Caliciviridae, includes enteric viruses of humans and domestic animals. Information on sapovirus infection of wildlife is limited and is currently lacking for any free-ranging wildlife species in Africa. By screening a large number of predominantly fecal samples (n = 631) obtained from five carnivore species in the Serengeti ecosystem, East Africa, sapovirus RNA was detected in the spotted hyena (Crocuta crocuta, family Hyaenidae), African lion (Panthera leo, family Felidae), and bat-eared fox (Otocyon megalotis, family Canidae), but not in golden or silver-backed jackals (Canis aureus and C. mesomelas, respectively, family Canidae). A phylogenetic analysis based on partial RNA-dependent RNA polymerase (RdRp) gene sequences placed the sapovirus strains from African carnivores in a monophyletic group. Within this monophyletic group, sapovirus strains from spotted hyenas formed one independent sub-group, and those from bat-eared fox and African lion a second sub-group. The percentage nucleotide similarity between sapoviruses from African carnivores and those from other species was low (< 70.4%). Long-term monitoring of sapovirus in a population of individually known spotted hyenas from 2001 to 2012 revealed: i) a relatively high overall infection prevalence (34.8%); ii) the circulation of several genetically diverse variants; iii) large fluctuations in infection prevalence across years, indicative of outbreaks; iv) no significant difference in the likelihood of infection between animals in different age categories. The likelihood of sapovirus infection decreased with increasing hyena group size, suggesting an encounter reduction effect, but was independent of socially mediated ano-genital contact, or the extent of the area over which an individual roamed.",2016 Sep 23,"['Olarte-Castillo, Ximena A.', 'Hofer, Heribert', 'Goller, Katja V.', 'Martella, Vito', 'Moehlman, Patricia D.', 'East, Marion L.']",PLoS One,,,False
c29b35526bc17c92bdcc277b303bd6fc3ab57b0a,PMC,The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus,http://dx.doi.org/10.1186/s12918-016-0336-6,PMC5035469,27663205,CC BY,"BACKGROUND: The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ anti-immune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation. RESULTS: We validated our predictions in 18 different knockout (KO) mouse strains, showing that network topology provides significant predictive power to identify genes that are important for viral infection. We identified a novel player in the immune response to virus infection, Kepi, an inhibitory subunit of the protein phosphatase 1 (PP1) complex, which protects against SARS-CoV pathogenesis. We also found that receptors for the proinflammatory cytokine tumor necrosis factor alpha (TNFα) promote pathogenesis, presumably through excessive inflammation. CONCLUSIONS: The current study provides validation of network modeling approaches for identifying important players in virus infection pathogenesis, and a step forward in understanding the host response to an important infectious disease. The results presented here suggest the role of Kepi in the host response to SARS-CoV, as well as inflammatory activity driving pathogenesis through TNFα signaling in SARS-CoV infections. Though we have reported the utility of this approach in bacterial and cell culture studies previously, this is the first comprehensive study to confirm that network topology can be used to predict phenotypes in mice with experimental validation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12918-016-0336-6) contains supplementary material, which is available to authorized users.",2016 Sep 23,"['McDermott, Jason E.', 'Mitchell, Hugh D.', 'Gralinski, Lisa E.', 'Eisfeld, Amie J.', 'Josset, Laurence', 'Bankhead, Armand', 'Neumann, Gabriele', 'Tilton, Susan C.', 'Schäfer, Alexandra', 'Li, Chengjun', 'Fan, Shufang', 'McWeeney, Shannon', 'Baric, Ralph S.', 'Katze, Michael G.', 'Waters, Katrina M.']",BMC Syst Biol,,,False
671eba2ccb7c435efe6f91d4065f446a27c8efba,PMC,The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus,http://dx.doi.org/10.1186/s12918-016-0336-6,PMC5035469,27663205,CC BY,"BACKGROUND: The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ anti-immune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation. RESULTS: We validated our predictions in 18 different knockout (KO) mouse strains, showing that network topology provides significant predictive power to identify genes that are important for viral infection. We identified a novel player in the immune response to virus infection, Kepi, an inhibitory subunit of the protein phosphatase 1 (PP1) complex, which protects against SARS-CoV pathogenesis. We also found that receptors for the proinflammatory cytokine tumor necrosis factor alpha (TNFα) promote pathogenesis, presumably through excessive inflammation. CONCLUSIONS: The current study provides validation of network modeling approaches for identifying important players in virus infection pathogenesis, and a step forward in understanding the host response to an important infectious disease. The results presented here suggest the role of Kepi in the host response to SARS-CoV, as well as inflammatory activity driving pathogenesis through TNFα signaling in SARS-CoV infections. Though we have reported the utility of this approach in bacterial and cell culture studies previously, this is the first comprehensive study to confirm that network topology can be used to predict phenotypes in mice with experimental validation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12918-016-0336-6) contains supplementary material, which is available to authorized users.",2016 Sep 23,"['McDermott, Jason E.', 'Mitchell, Hugh D.', 'Gralinski, Lisa E.', 'Eisfeld, Amie J.', 'Josset, Laurence', 'Bankhead, Armand', 'Neumann, Gabriele', 'Tilton, Susan C.', 'Schäfer, Alexandra', 'Li, Chengjun', 'Fan, Shufang', 'McWeeney, Shannon', 'Baric, Ralph S.', 'Katze, Michael G.', 'Waters, Katrina M.']",BMC Syst Biol,,,False
a137eb51461b4a4ed3980aa5b9cb2f2c1cf0292a,PMC,The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus,http://dx.doi.org/10.1186/s12918-016-0336-6,PMC5035469,27663205,CC BY,"BACKGROUND: The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ anti-immune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation. RESULTS: We validated our predictions in 18 different knockout (KO) mouse strains, showing that network topology provides significant predictive power to identify genes that are important for viral infection. We identified a novel player in the immune response to virus infection, Kepi, an inhibitory subunit of the protein phosphatase 1 (PP1) complex, which protects against SARS-CoV pathogenesis. We also found that receptors for the proinflammatory cytokine tumor necrosis factor alpha (TNFα) promote pathogenesis, presumably through excessive inflammation. CONCLUSIONS: The current study provides validation of network modeling approaches for identifying important players in virus infection pathogenesis, and a step forward in understanding the host response to an important infectious disease. The results presented here suggest the role of Kepi in the host response to SARS-CoV, as well as inflammatory activity driving pathogenesis through TNFα signaling in SARS-CoV infections. Though we have reported the utility of this approach in bacterial and cell culture studies previously, this is the first comprehensive study to confirm that network topology can be used to predict phenotypes in mice with experimental validation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12918-016-0336-6) contains supplementary material, which is available to authorized users.",2016 Sep 23,"['McDermott, Jason E.', 'Mitchell, Hugh D.', 'Gralinski, Lisa E.', 'Eisfeld, Amie J.', 'Josset, Laurence', 'Bankhead, Armand', 'Neumann, Gabriele', 'Tilton, Susan C.', 'Schäfer, Alexandra', 'Li, Chengjun', 'Fan, Shufang', 'McWeeney, Shannon', 'Baric, Ralph S.', 'Katze, Michael G.', 'Waters, Katrina M.']",BMC Syst Biol,,,True
a3718ef8f5fc2e8b32992c568bc66646a870656c,PMC,Emergence of human caliciviruses among diarrhea cases in southwest China,http://dx.doi.org/10.1186/s12879-016-1831-5,PMC5035476,27663519,CC BY,"BACKGROUND: Acute diarrhea is one of the most serious problems in global public health that causes considerable morbidity and mortality worldwide. Human caliciviruses (HuCV) including norovirus (NoV, genogroup GI and GII) and sapovirus (SaV), is a leading cause of acute sporadic diarrhea in individuals across all age groups. However, few studies had been conducted clarifying the characteristics of HuCV in diarrhea cases across all age groups in China. Our study was aimed at assessing the HuCV-related diarrhea burden and NoV genotypes distribution in southwest China. METHODS: The study was conducted in four hospitals in Kunming city, Yunnan province, from June 2014 to July 2015. Stool specimens were collected from 1,121 diarrhea cases and 319 healthy controls in outpatient departments. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect NoV (GI, GII) and SaV. Sequencing was applied to confirm the three viral infections and phylogenetic analysis was performed to determine their genotypes. A structured questionnaire was used to record the demographic information and clinical symptoms of subjects. RESULTS: HuCV was detected at an 11.0 % infection rate in 1,121 diarrhea cases and at 3.4 % rate in 319 non-diarrhea subjects (p < 0.0001, OR = 3.5, 95 % CI 1.8–6.5). The prevalence of the NoV genogroup GII and genotype GII.4 in diarrhea cases was significantly higher than that found in healthy controls (p < 0.0001, p = 0.018, respectively). NoV GII (n = 118, 10.5 %) was the most common HuCV subtype in diarrhea cases, followed by SaV (n = 3, 0.3 %) and NoV GI (n = 2, 0.2 %). Of 118 NoV GII strains isolated from diarrhea patients. GII.4 (n = 55, 46.6 %) was the predominant strain, followed by GII.3 (n = 28, 23.7 %), GII.12 (n = 25, 21.2 %), GII.17 (n = 8, 6.8 %), and GII.5 (n = 2, 1.7 %). Of the 55 GII.4 strains, the GII.4 Sydney 2012 variant had absolutely predominant prevalence (n = 52, 94.5 %), followed by the NoV GII.4-2006b variant (n = 3, 5.5 %). The GII.4 Orleans 2009 variant was not found in diarrhea cases of the study. CONCLUSIONS: NoV GII was the major genogroup and GII.4 was the most predominant strain detected in diarrhea patients. The GII.17 is an emergent variant in sporadic diarrhea and might become the predominant strain in diarrhea cases in the near future. Rapid, accurate detection kits need to be developed to help us find and treat NoV-associated diarrhea in clinical settings in a timely manner.",2016 Sep 23,"['Zhang, Shun-Xian', 'Li, Li', 'Yin, Jian-Wen', 'Jin, Miao', 'Kong, Xiang-Yu', 'Pang, Li-Li', 'Zhou, Yong-Kang', 'Tian, Li-Guang', 'Chen, Jia-Xu', 'Zhou, Xiao-Nong']",BMC Infect Dis,,,True
b3d7fd02de63c9e801c668f9784a1f31be59cc97,PMC,Identification of a novel canine parvovirus type 2c in Taiwan,http://dx.doi.org/10.1186/s12985-016-0620-5,PMC5035481,27663840,CC BY,"BACKGROUND: Taiwan has been considered free from canine parvovirus type 2c (CPV-2c) based on the last report of canine parvovirus type 2 (CPV-2) surveillance. However, since January 2015, the first report of CPV-2c in a puppy has occurred in Taiwan. There is currently limited information about the CPV-2c variant in Taiwan. In the present study, we characterized the previously unidentified CPV-2c variant and investigated the distribution of CPV-2 variants in Taiwan. METHODS: During January 2014 to April 2016, fecal or rectal swab samples from 99 dogs with suspected CPV-2 infection in Taiwan were collected. Eighty-eight were identified as being either CPV-2a, −2b or -2c variants positive by real-time PCR and sequence analysis. RESULTS: Sequence analysis of the 88 isolates confirmed CPV-2c as the dominant variant (54.6 %), followed by CPV-2b (26.1 %) and CPV-2a (19.3 %). Phylogenetic analysis demonstrated that the recent CPV-2c variants are similar to the Chinese CPV-2c strain but can be considered as novel Asian CPV-2c isolates. CONCLUSION: The present study provides evidence for the existence of a novel CPV-2c variant in Taiwan. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0620-5) contains supplementary material, which is available to authorized users.",2016 Sep 23,"['Chiang, Shu-Yun', 'Wu, Hung-Yi', 'Chiou, Ming-Tang', 'Chang, Min-Chen', 'Lin, Chao-Nan']",Virol J,,,True
a293d2836c440402c8f71b2785b853473d188f5e,PMC,Bibliometric analysis of global scientific research on carbapenem resistance (1986–2015),http://dx.doi.org/10.1186/s12941-016-0169-6,PMC5035509,27663999,CC BY,"BACKGROUND: Antimicrobial resistance is a global public health challenge and carbapenem resistance, in particular, is considered an urgent global health threat. This study was carried out to give a bibliometric overview of literature on carbapenem resistance. In specific, number of publications, top productive countries and institutes, highly cited articles, citation analysis, co-authorships, international collaboration, top active authors, and journals publishing articles on carbapenem resistance were analyzed and discussed. METHODS: Specific keywords pertaining to carbapenem resistance were used in Scopus database. Quantitative and qualitative analysis of retrieved data were presented using appropriate bibliometric indicators and visualization maps. RESULTS: A total of 2617 journal articles were retrieved. The average number of citations per article was of 21.47. The growth of publications showed a dramatic increase from 2008 to 2015. Approximately 9 % of retrieved articles on carbapenem resistance were published in Antimicrobial Agents and Chemotherapy journal. Retrieved articles were published by 102 different countries. The United States of America (USA) contributed most with 437 (16.70 %) articles followed by China with 257 (9.82 %) articles. When productivity was stratified by population size, Greece ranked first followed by France. Greece also ranked first when data were stratified by gross domestic product (GDP). Asian countries have lesser international collaboration compared with other countries in the top ten list. Five of top ten productive institutes were Europeans (France, the UK, Greece, Italy, and Switzerland) and two were Asians (China and South Korea). Other active institutes included an Israeli and a Brazilian institute. Four of the top ten cited articles were published in Antimicrobial Agents and Chemotherapy journal and two were published in The Lancet Infectious Diseases. CONCLUSION: There was a dramatic increase in number of publications on carbapenem resistance in the past few years. These publications were produced from different world regions including Asia, Europe, Middle East, and Latin America. International collaboration needs to be encouraged particularly for researchers in Asia. Molecular biology and epidemiology dominated the theme of the top ten cited articles on carbapenem resistance. This bibliometric study will hopefully help health policy makers in planning future research and allocating funds pertaining to carbapenem resistance.",2016 Sep 23,"['Sweileh, Waleed M.', 'Shraim, Naser Y.', 'Al-Jabi, Samah W.', 'Sawalha, Ansam F.', 'AbuTaha, Adham S.', 'Zyoud, Sa’ed H.']",Ann Clin Microbiol Antimicrob,,,True
bee044e4101c6958db139f19f6dd751990c2ce85,PMC,"Novel highly divergent reassortant bat rotaviruses in Cameroon, without evidence of zoonosis",http://dx.doi.org/10.1038/srep34209,PMC5035928,27666390,CC BY,"Bats are an important reservoir for zoonotic viruses. To date, only three RVA strains have been reported in bats in Kenya and China. In the current study we investigated the genetic diversity of RVAs in fecal samples from 87 straw-colored fruit bats living in close contact with humans in Cameroon using viral metagenomics. Five (near) complete RVA genomes were obtained. A single RVA strain showed a partial relationship with the Kenyan bat RVA strain, whereas the other strains were completely novel. Only the VP7 and VP4 genes showed significant variability, indicating the occurrence of frequent reassortment events. Comparing these bat RVA strains with currently used human RVA screening primers indicated that most of the novel VP7 and VP4 segments would not be detected in routine epidemiological screening studies. Therefore, novel consensus screening primers were developed and used to screen samples from infants with gastroenteritis living in close proximity with the studied bat population. Although RVA infections were identified in 36% of the infants, there was no evidence of zoonosis. This study identified multiple novel bat RVA strains, but further epidemiological studies in humans will have to assess if these viruses have the potential to cause gastroenteritis in humans.",2016 Sep 26,"['Yinda, Claude Kwe', 'Zeller, Mark', 'Conceição-Neto, Nádia', 'Maes, Piet', 'Deboutte, Ward', 'Beller, Leen', 'Heylen, Elisabeth', 'Ghogomu, Stephen Mbigha', 'Van Ranst, Marc', 'Matthijnssens, Jelle']",Sci Rep,,,True
afdacf564888d252a93303eb6f3407b8c3f3355c,PMC,"Novel highly divergent reassortant bat rotaviruses in Cameroon, without evidence of zoonosis",http://dx.doi.org/10.1038/srep34209,PMC5035928,27666390,CC BY,"Bats are an important reservoir for zoonotic viruses. To date, only three RVA strains have been reported in bats in Kenya and China. In the current study we investigated the genetic diversity of RVAs in fecal samples from 87 straw-colored fruit bats living in close contact with humans in Cameroon using viral metagenomics. Five (near) complete RVA genomes were obtained. A single RVA strain showed a partial relationship with the Kenyan bat RVA strain, whereas the other strains were completely novel. Only the VP7 and VP4 genes showed significant variability, indicating the occurrence of frequent reassortment events. Comparing these bat RVA strains with currently used human RVA screening primers indicated that most of the novel VP7 and VP4 segments would not be detected in routine epidemiological screening studies. Therefore, novel consensus screening primers were developed and used to screen samples from infants with gastroenteritis living in close proximity with the studied bat population. Although RVA infections were identified in 36% of the infants, there was no evidence of zoonosis. This study identified multiple novel bat RVA strains, but further epidemiological studies in humans will have to assess if these viruses have the potential to cause gastroenteritis in humans.",2016 Sep 26,"['Yinda, Claude Kwe', 'Zeller, Mark', 'Conceição-Neto, Nádia', 'Maes, Piet', 'Deboutte, Ward', 'Beller, Leen', 'Heylen, Elisabeth', 'Ghogomu, Stephen Mbigha', 'Van Ranst, Marc', 'Matthijnssens, Jelle']",Sci Rep,,,False
9c776ca426a931dbbd3e34cd0b817adb19add3f1,PMC,How Polyomaviruses Exploit the ERAD Machinery to Cause Infection,http://dx.doi.org/10.3390/v8090242,PMC5035956,27589785,CC BY,"To infect cells, polyomavirus (PyV) traffics from the cell surface to the endoplasmic reticulum (ER) where it hijacks elements of the ER-associated degradation (ERAD) machinery to penetrate the ER membrane and reach the cytosol. From the cytosol, the virus transports to the nucleus, enabling transcription and replication of the viral genome that leads to lytic infection or cellular transformation. How PyV exploits the ERAD machinery to cross the ER membrane and access the cytosol, a decisive infection step, remains enigmatic. However, recent studies have slowly unraveled many aspects of this process. These emerging insights should advance our efforts to develop more effective therapies against PyV-induced human diseases.",2016 Aug 29,"['Dupzyk, Allison', 'Tsai, Billy']",Viruses,,,True
8befe1b5905e502b127ae478f3b9de1d6e25e317,PMC,Arms Race between Enveloped Viruses and the Host ERAD Machinery,http://dx.doi.org/10.3390/v8090255,PMC5035969,27657106,CC BY,"Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during the infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed to potentiate or inhibit viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells.",2016 Sep 19,"['Frabutt, Dylan A.', 'Zheng, Yong-Hui']",Viruses,,,True
958d54d13cbc0341fe590ba4eeb59e2a0b4fca51,PMC,TRIM52 inhibits Japanese Encephalitis Virus replication by degrading the viral NS2A,http://dx.doi.org/10.1038/srep33698,PMC5035999,27667714,CC BY,"The members of tripartite-motif containing (TRIM) protein participate in various cellular processes and play an important role in host antiviral function. TRIM proteins exert their antiviral activity either directly by degrading viral proteins through their E3 ligase activity, or indirectly by promoting host innate immunity. This study demonstrated for the first time that TRIM52 is a novel antiviral TRIM protein against Japanese encephalitis virus (JEV) infection. Overexpression of TRIM52 restricted JEV replication in BHK-21 and 293T cells. In addition, JEV nonstructural protein 2A (NS2A) is a protein that interacts with TRIM52. Their interaction degraded NS2A in a proteasome-dependent manner via the E3 ligase activity of TRIM52. Thus, TRIM52 is a novel antiviral TRIM protein, and it exerted antiviral activity against JEV infection by targeting and degrading viral NS2A.",2016 Sep 26,"['Fan, Wenchun', 'Wu, Mengge', 'Qian, Suhong', 'Zhou, Yun', 'Chen, Huanchun', 'Li, Xiangmin', 'Qian, Ping']",Sci Rep,,,True
bba54a43464e4fda9280139894c5467524ef2faf,PMC,Rational improvement of gp41-targeting HIV-1 fusion inhibitors: an innovatively designed Ile-Asp-Leu tail with alternative conformations,http://dx.doi.org/10.1038/srep31983,PMC5036048,27666394,CC BY,"Peptides derived from the C-terminal heptad repeat (CHR) of HIV gp41 have been developed as effective fusion inhibitors against HIV-1, but facing the challenges of enhancing potency and stability. Here, we report a rationally designed novel HIV-1 fusion inhibitor derived from CHR-derived peptide (Trp628~Gln653, named CP), but with an innovative Ile-Asp-Leu tail (IDL) that dramatically increased the inhibitory activity by up to 100 folds. We also determined the crystal structures of artificial fusion peptides N36- and N43-L6-CP-IDL. Although the overall structures of both fusion peptides share the canonical six-helix bundle (6-HB) configuration, their IDL tails adopt two different conformations: a one-turn helix with the N36, and a hook-like structure with the longer N43. Structural comparison showed that the hook-like IDL tail possesses a larger interaction interface with NHR than the helical one. Further molecular dynamics simulations of the two 6-HBs and isolated CP-IDL peptides suggested that hook-like form of IDL tail can be stabilized by its binding to NHR trimer. Therefore, CP-IDL has potential for further development as a new HIV fusion inhibitor, and this strategy could be widely used in developing artificial fusion inhibitors against HIV and other enveloped viruses.",2016 Sep 26,"['Zhu, Yun', 'Su, Shan', 'Qin, Lili', 'Wang, Qian', 'Shi, Lei', 'Ma, Zhenxuan', 'Tang, Jianchao', 'Jiang, Shibo', 'Lu, Lu', 'Ye, Sheng', 'Zhang, Rongguang']",Sci Rep,,,True
8903ed70c0e66c2bad50f57df3c885f7253cc2b8,PMC,Fragment-based discovery of a new family of non-peptidic small-molecule cyclophilin inhibitors with potent antiviral activities,http://dx.doi.org/10.1038/ncomms12777,PMC5036131,27652979,CC BY,"Cyclophilins are peptidyl-prolyl cis/trans isomerases (PPIase) that catalyse the interconversion of the peptide bond at proline residues. Several cyclophilins play a pivotal role in the life cycle of a number of viruses. The existing cyclophilin inhibitors, all derived from cyclosporine A or sanglifehrin A, have disadvantages, including their size, potential for side effects unrelated to cyclophilin inhibition and drug–drug interactions, unclear antiviral spectrum and manufacturing issues. Here we use a fragment-based drug discovery approach using nucleic magnetic resonance, X-ray crystallography and structure-based compound optimization to generate a new family of non-peptidic, small-molecule cyclophilin inhibitors with potent in vitro PPIase inhibitory activity and antiviral activity against hepatitis C virus, human immunodeficiency virus and coronaviruses. This family of compounds has the potential for broad-spectrum, high-barrier-to-resistance treatment of viral infections.",2016 Sep 22,"['Ahmed-Belkacem, Abdelhakim', 'Colliandre, Lionel', 'Ahnou, Nazim', 'Nevers, Quentin', 'Gelin, Muriel', 'Bessin, Yannick', 'Brillet, Rozenn', 'Cala, Olivier', 'Douguet, Dominique', 'Bourguet, William', 'Krimm, Isabelle', 'Pawlotsky, Jean-Michel', 'Guichou, Jean- François']",Nat Commun,,,True
b16129cfc36efc5d85192fbaa31d96799c98f8c5,PMC,Fragment-based discovery of a new family of non-peptidic small-molecule cyclophilin inhibitors with potent antiviral activities,http://dx.doi.org/10.1038/ncomms12777,PMC5036131,27652979,CC BY,"Cyclophilins are peptidyl-prolyl cis/trans isomerases (PPIase) that catalyse the interconversion of the peptide bond at proline residues. Several cyclophilins play a pivotal role in the life cycle of a number of viruses. The existing cyclophilin inhibitors, all derived from cyclosporine A or sanglifehrin A, have disadvantages, including their size, potential for side effects unrelated to cyclophilin inhibition and drug–drug interactions, unclear antiviral spectrum and manufacturing issues. Here we use a fragment-based drug discovery approach using nucleic magnetic resonance, X-ray crystallography and structure-based compound optimization to generate a new family of non-peptidic, small-molecule cyclophilin inhibitors with potent in vitro PPIase inhibitory activity and antiviral activity against hepatitis C virus, human immunodeficiency virus and coronaviruses. This family of compounds has the potential for broad-spectrum, high-barrier-to-resistance treatment of viral infections.",2016 Sep 22,"['Ahmed-Belkacem, Abdelhakim', 'Colliandre, Lionel', 'Ahnou, Nazim', 'Nevers, Quentin', 'Gelin, Muriel', 'Bessin, Yannick', 'Brillet, Rozenn', 'Cala, Olivier', 'Douguet, Dominique', 'Bourguet, William', 'Krimm, Isabelle', 'Pawlotsky, Jean-Michel', 'Guichou, Jean- François']",Nat Commun,,,True
04ed44ad0aed30771e1ba0f38e4aa00101d1b8c3,PMC,A polyvalent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques,http://dx.doi.org/10.1038/ncomms12838,PMC5036149,27653379,CC BY,"As the predominant aetiological agent of the common cold, human rhinovirus (HRV) is the leading cause of human infectious disease. Early studies showed that a monovalent formalin-inactivated HRV vaccine can be protective, and virus-neutralizing antibodies (nAb) correlated with protection. However, co-circulation of many HRV types discouraged further vaccine efforts. Here, we test the hypothesis that increasing virus input titres in polyvalent inactivated HRV vaccine may result in broad nAb responses. We show that serum nAb against many rhinovirus types can be induced by polyvalent, inactivated HRVs plus alhydrogel (alum) adjuvant. Using formulations up to 25-valent in mice and 50-valent in rhesus macaques, HRV vaccine immunogenicity was related to sufficient quantity of input antigens, and valency was not a major factor for potency or breadth of the response. Thus, we have generated a vaccine capable of inducing nAb responses to numerous and diverse HRV types.",2016 Sep 22,"['Lee, Sujin', 'Nguyen, Minh Trang', 'Currier, Michael G.', 'Jenkins, Joe B.', 'Strobert, Elizabeth A.', 'Kajon, Adriana E.', 'Madan-Lala, Ranjna', 'Bochkov, Yury A.', 'Gern, James E.', 'Roy, Krishnendu', 'Lu, Xiaoyan', 'Erdman, Dean D.', 'Spearman, Paul', 'Moore, Martin L.']",Nat Commun,,,True
fc8c37b262255f1af7df6aa9bbbce30f5d5aa20a,PMC,A polyvalent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques,http://dx.doi.org/10.1038/ncomms12838,PMC5036149,27653379,CC BY,"As the predominant aetiological agent of the common cold, human rhinovirus (HRV) is the leading cause of human infectious disease. Early studies showed that a monovalent formalin-inactivated HRV vaccine can be protective, and virus-neutralizing antibodies (nAb) correlated with protection. However, co-circulation of many HRV types discouraged further vaccine efforts. Here, we test the hypothesis that increasing virus input titres in polyvalent inactivated HRV vaccine may result in broad nAb responses. We show that serum nAb against many rhinovirus types can be induced by polyvalent, inactivated HRVs plus alhydrogel (alum) adjuvant. Using formulations up to 25-valent in mice and 50-valent in rhesus macaques, HRV vaccine immunogenicity was related to sufficient quantity of input antigens, and valency was not a major factor for potency or breadth of the response. Thus, we have generated a vaccine capable of inducing nAb responses to numerous and diverse HRV types.",2016 Sep 22,"['Lee, Sujin', 'Nguyen, Minh Trang', 'Currier, Michael G.', 'Jenkins, Joe B.', 'Strobert, Elizabeth A.', 'Kajon, Adriana E.', 'Madan-Lala, Ranjna', 'Bochkov, Yury A.', 'Gern, James E.', 'Roy, Krishnendu', 'Lu, Xiaoyan', 'Erdman, Dean D.', 'Spearman, Paul', 'Moore, Martin L.']",Nat Commun,,,True
7acc1a3baf89f2341feebef298a6531b4f930794,PMC,Early diagnosis of dengue disease severity in a resource-limited Asian country,http://dx.doi.org/10.1186/s12879-016-1849-8,PMC5036306,27670906,CC BY,"BACKGROUND: Dengue is endemic throughout Cambodia, a country faced with significant health and economic challenges. We undertook a clinical study at the National Paediatric Hospital in Phnom Penh to evaluate clinical diagnostic parameters for dengue and predictors of disease outcome. METHODS: Between September 2011 and January 2013, all consecutive inpatients aged between 1 and 15 years and presenting with suspected dengue were enrolled. They were clinically assessed using both the 1997 and 2009 WHO dengue classifications. Specimens were collected upon admission and discharge and tested for dengue at Institut Pasteur in Cambodia. RESULTS: A total of 701 patients were screened. Of these, 79 % were dengue-confirmed by laboratory testing, and 21 % tested dengue-negative. A positive tourniquet test, absence of upper respiratory symptoms, leukopenia, thrombocytopenia, and elevated liver transaminases were independent predictors for laboratory-confirmed dengue among the children. The presence of several warning signs on hospital admission was associated with a concurrent laboratory-confirmed diagnosis of severe disease outcome. CONCLUSIONS: The presence of two or more warning signs was associated with a concurrent laboratory-confirmed diagnosis of severe dengue at hospital admission. Thus, a cumulative score combining simple clinical parameters and first-line laboratory findings could be used to accurately predict dengue virus infection in pediatric populations, optimizing triage in settings with limited laboratory resources. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1849-8) contains supplementary material, which is available to authorized users.",2016 Sep 26,"['Cavailler, Philippe', 'Tarantola, Arnaud', 'Leo, Yee Sin', 'Lover, Andrew A.', 'Rachline, Anne', 'Duch, Moniboth', 'Huy, Rekol', 'Quake, Ai Li', 'Kdan, Yuvatha', 'Duong, Veasna', 'Brett, Jeremy L.', 'Buchy, Philippe']",BMC Infect Dis,,,False
b21cd46320a65645b81f4187e79d00da23e72c4a,PMC,Early diagnosis of dengue disease severity in a resource-limited Asian country,http://dx.doi.org/10.1186/s12879-016-1849-8,PMC5036306,27670906,CC BY,"BACKGROUND: Dengue is endemic throughout Cambodia, a country faced with significant health and economic challenges. We undertook a clinical study at the National Paediatric Hospital in Phnom Penh to evaluate clinical diagnostic parameters for dengue and predictors of disease outcome. METHODS: Between September 2011 and January 2013, all consecutive inpatients aged between 1 and 15 years and presenting with suspected dengue were enrolled. They were clinically assessed using both the 1997 and 2009 WHO dengue classifications. Specimens were collected upon admission and discharge and tested for dengue at Institut Pasteur in Cambodia. RESULTS: A total of 701 patients were screened. Of these, 79 % were dengue-confirmed by laboratory testing, and 21 % tested dengue-negative. A positive tourniquet test, absence of upper respiratory symptoms, leukopenia, thrombocytopenia, and elevated liver transaminases were independent predictors for laboratory-confirmed dengue among the children. The presence of several warning signs on hospital admission was associated with a concurrent laboratory-confirmed diagnosis of severe disease outcome. CONCLUSIONS: The presence of two or more warning signs was associated with a concurrent laboratory-confirmed diagnosis of severe dengue at hospital admission. Thus, a cumulative score combining simple clinical parameters and first-line laboratory findings could be used to accurately predict dengue virus infection in pediatric populations, optimizing triage in settings with limited laboratory resources. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1849-8) contains supplementary material, which is available to authorized users.",2016 Sep 26,"['Cavailler, Philippe', 'Tarantola, Arnaud', 'Leo, Yee Sin', 'Lover, Andrew A.', 'Rachline, Anne', 'Duch, Moniboth', 'Huy, Rekol', 'Quake, Ai Li', 'Kdan, Yuvatha', 'Duong, Veasna', 'Brett, Jeremy L.', 'Buchy, Philippe']",BMC Infect Dis,,,False
1bef85a33a74c3d1765752da0e715fc3a46e00d8,PMC,Early diagnosis of dengue disease severity in a resource-limited Asian country,http://dx.doi.org/10.1186/s12879-016-1849-8,PMC5036306,27670906,CC BY,"BACKGROUND: Dengue is endemic throughout Cambodia, a country faced with significant health and economic challenges. We undertook a clinical study at the National Paediatric Hospital in Phnom Penh to evaluate clinical diagnostic parameters for dengue and predictors of disease outcome. METHODS: Between September 2011 and January 2013, all consecutive inpatients aged between 1 and 15 years and presenting with suspected dengue were enrolled. They were clinically assessed using both the 1997 and 2009 WHO dengue classifications. Specimens were collected upon admission and discharge and tested for dengue at Institut Pasteur in Cambodia. RESULTS: A total of 701 patients were screened. Of these, 79 % were dengue-confirmed by laboratory testing, and 21 % tested dengue-negative. A positive tourniquet test, absence of upper respiratory symptoms, leukopenia, thrombocytopenia, and elevated liver transaminases were independent predictors for laboratory-confirmed dengue among the children. The presence of several warning signs on hospital admission was associated with a concurrent laboratory-confirmed diagnosis of severe disease outcome. CONCLUSIONS: The presence of two or more warning signs was associated with a concurrent laboratory-confirmed diagnosis of severe dengue at hospital admission. Thus, a cumulative score combining simple clinical parameters and first-line laboratory findings could be used to accurately predict dengue virus infection in pediatric populations, optimizing triage in settings with limited laboratory resources. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1849-8) contains supplementary material, which is available to authorized users.",2016 Sep 26,"['Cavailler, Philippe', 'Tarantola, Arnaud', 'Leo, Yee Sin', 'Lover, Andrew A.', 'Rachline, Anne', 'Duch, Moniboth', 'Huy, Rekol', 'Quake, Ai Li', 'Kdan, Yuvatha', 'Duong, Veasna', 'Brett, Jeremy L.', 'Buchy, Philippe']",BMC Infect Dis,,,True
3ccac237e5fa57c9d28f59f0b9b8e58188edd29b,PMC,Influenza A Virus Polymerase Recruits the RNA Helicase DDX19 to Promote the Nuclear Export of Viral mRNAs,http://dx.doi.org/10.1038/srep33763,PMC5037575,27653209,CC BY,"Enhancing the knowledge of host factors that are required for efficient influenza A virus (IAV) replication is essential to address questions related to pathogenicity and to identify targets for antiviral drug development. Here we focused on the interplay between IAV and DExD-box RNA helicases (DDX), which play a key role in cellular RNA metabolism by remodeling RNA-RNA or RNA-protein complexes. We performed a targeted RNAi screen on 35 human DDX proteins to identify those involved in IAV life cycle. DDX19 was a major hit. In DDX19-depleted cells the accumulation of viral RNAs and proteins was delayed, and the production of infectious IAV particles was strongly reduced. We show that DDX19 associates with intronless, unspliced and spliced IAV mRNAs and promotes their nuclear export. In addition, we demonstrate an RNA-independent association between DDX19 and the viral polymerase, that is modulated by the ATPase activity of DDX19. Our results provide a model in which DDX19 is recruited to viral mRNAs in the nucleus of infected cells to enhance their nuclear export. Information gained from this virus-host interaction improves the understanding of both the IAV replication cycle and the cellular function of DDX19.",2016 Sep 22,"['Diot, Cédric', 'Fournier, Guillaume', 'Dos Santos, Mélanie', 'Magnus, Julie', 'Komarova, Anastasia', 'van der Werf, Sylvie', 'Munier, Sandie', 'Naffakh, Nadia']",Sci Rep,,,True
695fe9211e014d362cf1d7a04fb81add693c12c5,PMC,Influenza A Virus Polymerase Recruits the RNA Helicase DDX19 to Promote the Nuclear Export of Viral mRNAs,http://dx.doi.org/10.1038/srep33763,PMC5037575,27653209,CC BY,"Enhancing the knowledge of host factors that are required for efficient influenza A virus (IAV) replication is essential to address questions related to pathogenicity and to identify targets for antiviral drug development. Here we focused on the interplay between IAV and DExD-box RNA helicases (DDX), which play a key role in cellular RNA metabolism by remodeling RNA-RNA or RNA-protein complexes. We performed a targeted RNAi screen on 35 human DDX proteins to identify those involved in IAV life cycle. DDX19 was a major hit. In DDX19-depleted cells the accumulation of viral RNAs and proteins was delayed, and the production of infectious IAV particles was strongly reduced. We show that DDX19 associates with intronless, unspliced and spliced IAV mRNAs and promotes their nuclear export. In addition, we demonstrate an RNA-independent association between DDX19 and the viral polymerase, that is modulated by the ATPase activity of DDX19. Our results provide a model in which DDX19 is recruited to viral mRNAs in the nucleus of infected cells to enhance their nuclear export. Information gained from this virus-host interaction improves the understanding of both the IAV replication cycle and the cellular function of DDX19.",2016 Sep 22,"['Diot, Cédric', 'Fournier, Guillaume', 'Dos Santos, Mélanie', 'Magnus, Julie', 'Komarova, Anastasia', 'van der Werf, Sylvie', 'Munier, Sandie', 'Naffakh, Nadia']",Sci Rep,,,False
634d9f6010d3e4f1586f4382b5c5c89e316d58bd,PMC,Success of tumorsphere isolation from WHO grade IV gliomas does not correlate with the weight of fresh tumor specimens: an immunohistochemical characterization of tumorsphere differentiation,http://dx.doi.org/10.1186/s12935-016-0350-1,PMC5037893,27708549,CC BY,"BACKGROUND: A trend of stage-by-stage increase in tumorsphere (TS) formation from glioma samples has been reported. Despite this trend, not all surgical specimens give rise to TSs, even World Health Organization (WHO) grade IV gliomas. Furthermore, it has been reported that differences in overall survival of primary glioblastoma patients depends on the propensity of their tumors to form TSs. However, the weights of fresh specimens vary from one surgical isolate to the next. METHODS: Accordingly, we evaluated the relationship between the weights of surgical specimens in WHO grade IV gliomas with the capacity to isolate TSs. Thirty-five fresh WHO grade IV glioma specimens were separated into two groups, based on whether they were positive or negative for TS isolation, and the relationship between TS isolation and weight of surgical specimens was assessed. RESULTS: We observed no significant difference in the weights of surgical samples in the two groups, and found that the optimal weight of specimens for TSs isolation was 500 mg. CONCLUSION: Thus, contrary to our expectations, the ability to isolate TSs from WHO grade IV glioma specimens was not related to the weight of fresh specimens.",2016 Sep 27,"['Sung, Kyoung Su', 'Shim, Jin-Kyoung', 'Lee, Ji-Hyun', 'Kim, Se Hoon', 'Park, Sohee', 'Roh, Tae-Hoon', 'Moon, Ju Hyung', 'Kim, Eui-Hyun', 'Kim, Sun Ho', 'Lee, Su Jae', 'Huh, Yong Min', 'Kang, Seok-Gu', 'Chang, Jong Hee']",Cancer Cell Int,,,True
3f551bf91d2b52cadac39dbd62e7ae0f51066446,PMC,A Bat-Derived Putative Cross-Family Recombinant Coronavirus with a Reovirus Gene,http://dx.doi.org/10.1371/journal.ppat.1005883,PMC5038965,27676249,CC BY,"The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 has generated enormous interest in the biodiversity, genomics and cross-species transmission potential of coronaviruses, especially those from bats, the second most speciose order of mammals. Herein, we identified a novel coronavirus, provisionally designated Rousettus bat coronavirus GCCDC1 (Ro-BatCoV GCCDC1), in the rectal swab samples of Rousettus leschenaulti bats by using pan-coronavirus RT-PCR and next-generation sequencing. Although the virus is similar to Rousettus bat coronavirus HKU9 (Ro-BatCoV HKU9) in genome characteristics, it is sufficiently distinct to be classified as a new species according to the criteria defined by the International Committee of Taxonomy of Viruses (ICTV). More striking was that Ro-BatCoV GCCDC1 contained a unique gene integrated into the 3’-end of the genome that has no homologs in any known coronavirus, but which sequence and phylogeny analyses indicated most likely originated from the p10 gene of a bat orthoreovirus. Subgenomic mRNA and cellular-level observations demonstrated that the p10 gene is functional and induces the formation of cell syncytia. Therefore, here we report a putative heterologous inter-family recombination event between a single-stranded, positive-sense RNA virus and a double-stranded segmented RNA virus, providing insights into the fundamental mechanisms of viral evolution.",2016 Sep 27,"['Huang, Canping', 'Liu, William J.', 'Xu, Wen', 'Jin, Tao', 'Zhao, Yingze', 'Song, Jingdong', 'Shi, Yi', 'Ji, Wei', 'Jia, Hao', 'Zhou, Yongming', 'Wen, Honghua', 'Zhao, Honglan', 'Liu, Huaxing', 'Li, Hong', 'Wang, Qihui', 'Wu, Ying', 'Wang, Liang', 'Liu, Di', 'Liu, Guang', 'Yu, Hongjie', 'Holmes, Edward C.', 'Lu, Lin', 'Gao, George F.']",PLoS Pathog,,,True
b07bcd8179099f8a5e49b8a7a2530590da99403b,PMC,The Role of Antimicrobial Peptides in Influenza Virus Infection and Their Potential as Antiviral and Immunomodulatory Therapy,http://dx.doi.org/10.3390/ph9030053,PMC5039506,27608030,CC BY,"Influenza A virus (IAV) remains a major threat that can cause severe morbidity and mortality due to rapid genomic variation. Resistance of IAVs to current anti-IAV drugs has been emerging, and antimicrobial peptides (AMPs) have been considered to be potential candidates for novel treatment against IAV infection. AMPs are endogenous proteins playing important roles in host defense through direct antimicrobial and antiviral activities and through immunomodulatory effects. In this review, we will discuss the anti-IAV and immunomodulatory effects of classical AMPs (defensins and cathelicidins), and proteins more recently discovered to have AMP-like activity (histones and Alzheimer’s associated β-amyloid). We will discuss the interactions between AMPs and other host defense proteins. Major emphasis will be placed on novel synthetic AMPs derived from modification of natural proteins, and on potential methods of increasing expression of endogenous AMPs, since these approaches may lead to novel antiviral therapeutics.",2016 Sep 6,"['Hsieh, I-Ni', 'Hartshorn, Kevan L.']",Pharmaceuticals (Basel),,,True
06624de6d8b09e5db9ba01c4cc721583331a40b5,PMC,Coinfection of Chlamydiae and other Bacteria in Reactive Arthritis and Spondyloarthritis: Need for Future Research,http://dx.doi.org/10.3390/microorganisms4030030,PMC5039590,27681924,CC BY,"Reactive (inflammatory) arthritis has been known for many years to follow genital infection with the intracellular bacterial pathogen Chlamydia trachomatis in some individuals. Recent studies from several groups have demonstrated that a related bacterium, the respiratory pathogen Chlamydia pneumoniae, can elicit a similar arthritis. Studies of these organisms, and of a set of gastrointestinal pathogens also associated with engendering inflammatory arthritis, have been relatively extensive. However, reports focusing on coinfections with these and/or other organisms, and the effects of such coinfections on the host immune and other systems, have been rare. In this article, we review the extant data regarding infections by multiple pathogens in the joint as they relate to engendering arthritis, and we suggest a number of research areas that must be given a high priority if we are to understand, and therefore to treat in an effective manner, such arthritides.",2016 Aug 24,"['Zeidler, Henning', 'Hudson, Alan P']",Microorganisms,,,True
95e77fc95e5b3b35c8856061119f2474d61c6089,PMC,The hookworm Ancylostoma ceylanicum intestinal transcriptome provides a platform for selecting drug and vaccine candidates,http://dx.doi.org/10.1186/s13071-016-1795-8,PMC5039805,27677574,CC BY,"BACKGROUND: The intestine of hookworms contains enzymes and proteins involved in the blood-feeding process of the parasite and is therefore a promising source of possible vaccine antigens. One such antigen, the hemoglobin-digesting intestinal aspartic protease known as Na-APR-1 from the human hookworm Necator americanus, is currently a lead candidate antigen in clinical trials, as is Na-GST-1 a heme-detoxifying glutathione S-transferase. METHODS: In order to discover additional hookworm vaccine antigens, messenger RNA was obtained from the intestine of male hookworms, Ancylostoma ceylanicum, maintained in hamsters. RNA-seq was performed using Illumina high-throughput sequencing technology. The genes expressed in the hookworm intestine were compared with those expressed in the whole worm and those genes overexpressed in the parasite intestine transcriptome were further analyzed. RESULTS: Among the lead transcripts identified were genes encoding for proteolytic enzymes including an A. ceylanicum APR-1, but the most common proteases were cysteine-, serine-, and metallo-proteases. Also in abundance were specific transporters of key breakdown metabolites, including amino acids, glucose, lipids, ions and water; detoxifying and heme-binding glutathione S-transferases; a family of cysteine-rich/antigen 5/pathogenesis-related 1 proteins (CAP) previously found in high abundance in parasitic nematodes; C-type lectins; and heat shock proteins. These candidates will be ranked for downstream antigen target selection based on key criteria including abundance, uniqueness in the parasite versus the vertebrate host, as well as solubility and yield of expression. CONCLUSION: The intestinal transcriptome of A. ceylanicum provides useful information for the identification of proteins involved in the blood-feeding process, representing a first step towards a reverse vaccinology approach to a human hookworm vaccine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1795-8) contains supplementary material, which is available to authorized users.",2016 Sep 27,"['Wei, Junfei', 'Damania, Ashish', 'Gao, Xin', 'Liu, Zhuyun', 'Mejia, Rojelio', 'Mitreva, Makedonka', 'Strych, Ulrich', 'Bottazzi, Maria Elena', 'Hotez, Peter J.', 'Zhan, Bin']",Parasit Vectors,,,False
a53cae6e96975f86052ebaee23f1b83f8b90d175,PMC,The hookworm Ancylostoma ceylanicum intestinal transcriptome provides a platform for selecting drug and vaccine candidates,http://dx.doi.org/10.1186/s13071-016-1795-8,PMC5039805,27677574,CC BY,"BACKGROUND: The intestine of hookworms contains enzymes and proteins involved in the blood-feeding process of the parasite and is therefore a promising source of possible vaccine antigens. One such antigen, the hemoglobin-digesting intestinal aspartic protease known as Na-APR-1 from the human hookworm Necator americanus, is currently a lead candidate antigen in clinical trials, as is Na-GST-1 a heme-detoxifying glutathione S-transferase. METHODS: In order to discover additional hookworm vaccine antigens, messenger RNA was obtained from the intestine of male hookworms, Ancylostoma ceylanicum, maintained in hamsters. RNA-seq was performed using Illumina high-throughput sequencing technology. The genes expressed in the hookworm intestine were compared with those expressed in the whole worm and those genes overexpressed in the parasite intestine transcriptome were further analyzed. RESULTS: Among the lead transcripts identified were genes encoding for proteolytic enzymes including an A. ceylanicum APR-1, but the most common proteases were cysteine-, serine-, and metallo-proteases. Also in abundance were specific transporters of key breakdown metabolites, including amino acids, glucose, lipids, ions and water; detoxifying and heme-binding glutathione S-transferases; a family of cysteine-rich/antigen 5/pathogenesis-related 1 proteins (CAP) previously found in high abundance in parasitic nematodes; C-type lectins; and heat shock proteins. These candidates will be ranked for downstream antigen target selection based on key criteria including abundance, uniqueness in the parasite versus the vertebrate host, as well as solubility and yield of expression. CONCLUSION: The intestinal transcriptome of A. ceylanicum provides useful information for the identification of proteins involved in the blood-feeding process, representing a first step towards a reverse vaccinology approach to a human hookworm vaccine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1795-8) contains supplementary material, which is available to authorized users.",2016 Sep 27,"['Wei, Junfei', 'Damania, Ashish', 'Gao, Xin', 'Liu, Zhuyun', 'Mejia, Rojelio', 'Mitreva, Makedonka', 'Strych, Ulrich', 'Bottazzi, Maria Elena', 'Hotez, Peter J.', 'Zhan, Bin']",Parasit Vectors,,,True
ca73d739c9c8c6ddb081d0badcea76f821ae147a,PMC,Rescue of the 1947 Zika Virus Prototype Strain with a Cytomegalovirus Promoter-Driven cDNA Clone,http://dx.doi.org/10.1128/mSphere.00246-16,PMC5040786,27704051,CC BY,"The recent Zika virus (ZIKV) outbreak has been linked to severe pathogenesis. Here, we report the construction of a plasmid carrying a cytomegalovirus (CMV) promoter-expressed prototype 1947 Uganda MR766 ZIKV cDNA that can initiate infection following direct plasmid DNA transfection of mammalian cells. Incorporation of a synthetic intron in the nonstructural protein 1 (NS1) region of the ZIKV polyprotein reduced viral cDNA-associated toxicity in bacteria. High levels of infectious virus were produced following transfection of the plasmid bearing the wild-type MR766 ZIKV genome, but not one with a disruption to the viral nonstructural protein 5 (NS5) polymerase active site. Multicycle growth curve and plaque assay experiments indicated that the MR766 virus resulting from plasmid transfection exhibited growth characteristics that were more similar to its parental isolate than previously published 2010 Cambodia and 2015 Brazil cDNA-rescued ZIKV. This ZIKV infectious clone will be useful for investigating the genetic determinants of ZIKV infection and pathogenesis and should be amenable to construction of diverse infectious clones expressing reporter proteins and representing a range of ZIKV isolates. IMPORTANCE The study of ZIKV, which has become increasingly important with the recent association of this virus with microcephaly and Guillain-Barré syndrome, would benefit from an efficient strategy to genetically manipulate the virus. This work describes a model system to produce infectious virus in cell culture. We created a plasmid carrying the prototype 1947 Uganda MR766 ZIKV genome that both was stable in bacteria and could produce high levels of infectious virus in mammalian cells through direct delivery of this DNA. Furthermore, growth properties of this rescued virus closely resembled those of the viral isolate from which it was derived. This model system will provide a simple and effective means to study how ZIKV genetics impact viral replication and pathogenesis.",2016 Sep 28,"['Schwarz, Megan C.', 'Sourisseau, Marion', 'Espino, Michael M.', 'Gray, Essanna S.', 'Chambers, Matthew T.', 'Tortorella, Domenico', 'Evans, Matthew J.']",mSphere,,,True
35ccd353aa1b7ee2a015dc8012a3bcc19a8f9a20,PMC,Strongyloides Hyperinfection Syndrome Combined with Cytomegalovirus Infection,http://dx.doi.org/10.1155/2016/1786265,PMC5040796,27703835,CC BY,"The mortality in Strongyloides hyperinfection syndrome (SHS) is alarmingly high. This is particularly common in bone marrow, renal, and other solid organ transplant (SOT) patients, where figures may reach up to 50–85%. Immunosuppressives, principally corticosteroids, are the primary triggering factor. In general, the clinical features of Strongyloides stercoralis hyperinfection are nonspecific; therefore, a high index of suspicion is required for early diagnosis and starting appropriate therapy. Although recurrent Gram-negative sepsis and meningitis have been previously reported, the combination of both cytomegalovirus (CMV) and strongyloidiasis had rarely been associated. We here describe a patient who survived SHS with recurrent Escherichia coli (E. coli) urosepsis and CMV infection.",2016 Sep 15,"['Elzein, Fatehi Elnour', 'Alsaeed, Mohammed', 'Ballool, Sulafa', 'Attia, Ashraf']",Case Rep Transplant,,,True
75a8ca179e8e0405a9c150507809c0f5c38aedb5,PMC,Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus,http://dx.doi.org/10.1038/srep34108,PMC5040956,27682426,CC BY,"The lack of a licensed vaccine for respiratory syncytial virus (RSV) can be partly attributed to regulatory hurdles resulting from vaccine enhanced respiratory disease (ERD) subsequent to natural RSV infection that was observed in clinical trials of formalin-inactivated RSV (FI-RSV) in antigen-naïve infants. To develop an effective vaccine that does not enhance RSV illness, it is important to understand how formalin and heat inactivation affected the antigenicity and immunogenicity of FI-RSV compared to native virus. Informed by atomic structures of RSV fusion (F) glycoprotein in prefusion (pre-F) and postfusion (post-F) conformations, we demonstrate that FI-RSV predominately presents post-F on the virion surface, whereas infectious RSV presents both pre-F and post-F conformations. This significant antigenic distinction has not been previously appreciated. Thus, a stabilized pre-F antigen is more representative of live RSV than F in its post-F conformation, as displayed on the surface of FI-RSV. This finding has major implications for discriminating current pre-F-based immunogens from FI-RSV used in historical vaccine trials.",2016 Sep 29,"['Killikelly, April M.', 'Kanekiyo, Masaru', 'Graham, Barney S.']",Sci Rep,,,True
f236858559d164c23558a5183e0c9302c5269e3c,PMC,Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus,http://dx.doi.org/10.1038/srep34108,PMC5040956,27682426,CC BY,"The lack of a licensed vaccine for respiratory syncytial virus (RSV) can be partly attributed to regulatory hurdles resulting from vaccine enhanced respiratory disease (ERD) subsequent to natural RSV infection that was observed in clinical trials of formalin-inactivated RSV (FI-RSV) in antigen-naïve infants. To develop an effective vaccine that does not enhance RSV illness, it is important to understand how formalin and heat inactivation affected the antigenicity and immunogenicity of FI-RSV compared to native virus. Informed by atomic structures of RSV fusion (F) glycoprotein in prefusion (pre-F) and postfusion (post-F) conformations, we demonstrate that FI-RSV predominately presents post-F on the virion surface, whereas infectious RSV presents both pre-F and post-F conformations. This significant antigenic distinction has not been previously appreciated. Thus, a stabilized pre-F antigen is more representative of live RSV than F in its post-F conformation, as displayed on the surface of FI-RSV. This finding has major implications for discriminating current pre-F-based immunogens from FI-RSV used in historical vaccine trials.",2016 Sep 29,"['Killikelly, April M.', 'Kanekiyo, Masaru', 'Graham, Barney S.']",Sci Rep,,,False
206231b403edaaa8ff0fd1a23ca2428dd261507b,PMC,Endophytes: A Treasure House of Bioactive Compounds of Medicinal Importance,http://dx.doi.org/10.3389/fmicb.2016.01538,PMC5041141,27746767,CC BY,"Endophytes are an endosymbiotic group of microorganisms that colonize in plants and microbes that can be readily isolated from any microbial or plant growth medium. They act as reservoirs of novel bioactive secondary metabolites, such as alkaloids, phenolic acids, quinones, steroids, saponins, tannins, and terpenoids that serve as a potential candidate for antimicrobial, anti-insect, anticancer and many more properties. While plant sources are being extensively explored for new chemical entities for therapeutic purposes, endophytic microbes also constitute an important source for drug discovery. This review aims to comprehend the contribution and uses of endophytes as an impending source of drugs against various forms of diseases and other possible medicinal use.",2016 Sep 29,"['Gouda, Sushanto', 'Das, Gitishree', 'Sen, Sandeep K.', 'Shin, Han-Seung', 'Patra, Jayanta Kumar']",Front Microbiol,,,True
2f0c1ffd323fc118bfa8cdd80142b126416423f9,PMC,The Golgi associated ERI3 is a Flavivirus host factor,http://dx.doi.org/10.1038/srep34379,PMC5041148,27682269,CC BY,"Dengue virus (DENV) is a mosquito-borne Flavivirus classified into four serotypes (DENV-1-4) that causes Dengue fever (DF), Dengue hemorrhagic Fever (DHF) or Dengue shock syndrome (DSS). An estimated 390 million people are at risk for infection with DENV and there are no effective vaccines or therapeutics. We utilized RNA chromatography coupled with quantitative mass spectrometry (qMS) to identify host RNA binding proteins (RBPs) that interact with DENV-2 RNA. We identified ERI3 (also PRNPIP and PINT1), a putative 3′–5′ RNA exonuclease, which preferentially associates with DENV-2 genomic RNA via interactions with dumbbell structures in the 3′ UTR. ERI3 is required for accumulation of DENV-2 genomic RNA and production of infectious particles. Furthermore, the mosquito homologue of ERI3 is required for DENV-2 replication in adult Aedes aegypti mosquitos implying that the requirement for ERI3 is conserved in both DENV hosts. In human cells ERI3 localizes to the Golgi in uninfected cells, but relocalizes near sites of DENV-2 replication in infected cells. ERI3 is not required for maintaining DENV-2 RNA stability or translation of the viral polyprotein, but is required for viral RNA synthesis. Our results define a specific role for ERI3 and highlight the importance of Golgi proteins in DENV-2 replication.",2016 Sep 29,"['Ward, Alex Michael', 'Calvert, Meredith E. K.', 'Read, Leah R.', 'Kang, Seokyoung', 'Levitt, Brandt E.', 'Dimopoulos, George', 'Bradrick, Shelton S.', 'Gunaratne, Jayantha', 'Garcia-Blanco, Mariano A.']",Sci Rep,,,True
dc46a9c2a3b3f5f7f3b6650c6fba4369a2793cd2,PMC,The Golgi associated ERI3 is a Flavivirus host factor,http://dx.doi.org/10.1038/srep34379,PMC5041148,27682269,CC BY,"Dengue virus (DENV) is a mosquito-borne Flavivirus classified into four serotypes (DENV-1-4) that causes Dengue fever (DF), Dengue hemorrhagic Fever (DHF) or Dengue shock syndrome (DSS). An estimated 390 million people are at risk for infection with DENV and there are no effective vaccines or therapeutics. We utilized RNA chromatography coupled with quantitative mass spectrometry (qMS) to identify host RNA binding proteins (RBPs) that interact with DENV-2 RNA. We identified ERI3 (also PRNPIP and PINT1), a putative 3′–5′ RNA exonuclease, which preferentially associates with DENV-2 genomic RNA via interactions with dumbbell structures in the 3′ UTR. ERI3 is required for accumulation of DENV-2 genomic RNA and production of infectious particles. Furthermore, the mosquito homologue of ERI3 is required for DENV-2 replication in adult Aedes aegypti mosquitos implying that the requirement for ERI3 is conserved in both DENV hosts. In human cells ERI3 localizes to the Golgi in uninfected cells, but relocalizes near sites of DENV-2 replication in infected cells. ERI3 is not required for maintaining DENV-2 RNA stability or translation of the viral polyprotein, but is required for viral RNA synthesis. Our results define a specific role for ERI3 and highlight the importance of Golgi proteins in DENV-2 replication.",2016 Sep 29,"['Ward, Alex Michael', 'Calvert, Meredith E. K.', 'Read, Leah R.', 'Kang, Seokyoung', 'Levitt, Brandt E.', 'Dimopoulos, George', 'Bradrick, Shelton S.', 'Gunaratne, Jayantha', 'Garcia-Blanco, Mariano A.']",Sci Rep,,,True
35fd455662a4a9c03d3791ee3a390c163a53f242,PMC,Phage display as a promising approach for vaccine development,http://dx.doi.org/10.1186/s12929-016-0285-9,PMC5041315,27680328,CC BY,"Bacteriophages are specific antagonists to bacterial hosts. These viral entities have attracted growing interest as optimal vaccine delivery vehicles. Phages are well-matched for vaccine design due to being highly stable under harsh environmental conditions, simple and inexpensive large scale production, and potent adjuvant capacities. Phage vaccines have efficient immunostimulatory effects and present a high safety profile because these viruses have made a constant relationship with the mammalian body during a long-standing evolutionary period. The birth of phage display technology has been a turning point in the development of phage-based vaccines. Phage display vaccines are made by expressing multiple copies of an antigen on the surface of immunogenic phage particles, thereby eliciting a powerful and effective immune response. Also, the ability to produce combinatorial peptide libraries with a highly diverse pool of randomized ligands has transformed phage display into a straightforward, versatile and high throughput screening methodology for the identification of potential vaccine candidates against different diseases in particular microbial infections. These libraries can be conveniently screened through an affinity selection-based strategy called biopanning against a wide variety of targets for the selection of mimotopes with high antigenicity and immunogenicity. Also, they can be panned against the antiserum of convalescent individuals to recognize novel peptidomimetics of pathogen-related epitopes. Phage display has represented enormous promise for finding new strategies of vaccine discovery and production and current breakthroughs promise a brilliant future for the development of different phage-based vaccine platforms.",2016 Sep 29,"['Aghebati-Maleki, Leili', 'Bakhshinejad, Babak', 'Baradaran, Behzad', 'Motallebnezhad, Morteza', 'Aghebati-Maleki, Ali', 'Nickho, Hamid', 'Yousefi, Mehdi', 'Majidi, Jafar']",J Biomed Sci,,,True
40f52a42602489ad329c93edf69e213267303c1f,PMC,Mandating influenza vaccinations for health care workers: analysing opportunities for policy change using Kingdon’s agenda setting framework,http://dx.doi.org/10.1186/s12913-016-1772-0,PMC5041441,27682853,CC BY,"BACKGROUND: The consequences of annual influenza outbreaks are often underestimated by the general public. Influenza poses a serious public health threat around the world, particularly for the most vulnerable populations. Fortunately, vaccination can mitigate the negative effects of this common infectious disease. Although inoculating frontline health care workers (HCWs) helps minimize disease transmission, some HCWs continue to resist participating in voluntary immunization programs. A potential solution to this problem is government-mandated vaccination for HCWs; however, in practice, there are substantial barriers to the adoption of such policies. The purpose of this paper is to identify the likelihood of adopting a policy for mandatory immunization of HCWs in Ontario based on a historical review of barriers to the agenda setting process. METHODS: Documents from secondary data sources were analysed using Kingdon’s agenda setting framework of three converging streams leading to windows of opportunity for possible policy adoption. RESULTS: The problems, politics, and policies streams of Kingdon’s framework have converged and diverged repeatedly over an extended period (policy windows have opened and closed several times). In each instance, a technically feasible solution was available. However, despite the evidence supporting the value of HCW immunization, alignment of the three agenda setting streams occurred for very short periods of time, during which, opposition lobby groups reacted, making the proposed solution less politically acceptable. CONCLUSIONS: Prior to the adoption of any new policies, issues must reach a government’s decision agenda. Based on Kingdon’s agenda setting framework, this only occurs when there is alignment of the problems, politics, and policies streams. Understanding this process makes it easier to predict the likelihood of a policy being adopted, and ultimately implemented. Such learning may be applied to policy issues in other jurisdictions. In the case of mandatory influenza vaccinations for HCWs in Ontario, it seems highly unlikely that a new policy will be adopted until perception of the problem’s importance is sufficient to overcome the political opposition to implementing a solution and thus, create a window of opportunity that is open long enough to support change.",2016 Sep 29,"['Jackson-Lee, Angela', 'Barr, Neil G.', 'Randall, Glen E.']",BMC Health Serv Res,,,True
50ad279de0a3f825b6280e07afc79439f59ecc3a,PMC,XB130 deficiency enhances lipopolysaccharide-induced septic response and acute lung injury,http://dx.doi.org/10.18632/oncotarget.8326,PMC5041914,27029000,CC BY,"XB130 is a novel oncoprotein that promotes cancer cell survival, proliferation and migration. Its physiological function in vivo is largely unknown. The objective of this study was to determine the role of XB130 in lipopolysaccharide (LPS)-induced septic responses and acute lung injury. LPS was intraperitoneally administrated to Xb130 knockout (KO) and wild type (WT) mice. There was a significant weight loss in KO mice at Day 2 and significantly higher disease scores during the 7 days of observation. The levels of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-6 and interleukin-10 in the serum were significantly higher in KO mice at Day 2. In KO mice there were a significantly higher lung injury score, higher wet/dry lung weight ratio, more apoptotic cells and less proliferative cells in the lung. Macrophage infiltration was significantly elevated in the lung of KO mice. There was significantly increased number of p-GSK-3β positive cells in KO mice, which were mainly neutrophils and macrophages. XB130 is expressed in alveolar type I and type II cells in the lung. The expression in these cells was significantly reduced after LPS challenge. XB130 deficiency delayed the recovery from systemic septic responses, and the presence of XB130 in the alveolar epithelial cells may provide protective mechanisms by reducing cell death and promoting cell proliferation, and reducing pulmonary permeability.",2016 Mar 23,"['Toba, Hiroaki', 'Tomankova, Tereza', 'Wang, Yingchun', 'Bai, Xiaohui', 'Cho, Hae-Ra', 'Guan, Zhehong', 'Adeyi, Oyedele A.', 'Tian, Feng', 'Keshavjee, Shaf', 'Liu, Mingyao']",Oncotarget,,,True
fbe53eb3d1e68e9fc27b44c51e31a039c08aeb52,PMC,XB130 deficiency enhances lipopolysaccharide-induced septic response and acute lung injury,http://dx.doi.org/10.18632/oncotarget.8326,PMC5041914,27029000,CC BY,"XB130 is a novel oncoprotein that promotes cancer cell survival, proliferation and migration. Its physiological function in vivo is largely unknown. The objective of this study was to determine the role of XB130 in lipopolysaccharide (LPS)-induced septic responses and acute lung injury. LPS was intraperitoneally administrated to Xb130 knockout (KO) and wild type (WT) mice. There was a significant weight loss in KO mice at Day 2 and significantly higher disease scores during the 7 days of observation. The levels of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-6 and interleukin-10 in the serum were significantly higher in KO mice at Day 2. In KO mice there were a significantly higher lung injury score, higher wet/dry lung weight ratio, more apoptotic cells and less proliferative cells in the lung. Macrophage infiltration was significantly elevated in the lung of KO mice. There was significantly increased number of p-GSK-3β positive cells in KO mice, which were mainly neutrophils and macrophages. XB130 is expressed in alveolar type I and type II cells in the lung. The expression in these cells was significantly reduced after LPS challenge. XB130 deficiency delayed the recovery from systemic septic responses, and the presence of XB130 in the alveolar epithelial cells may provide protective mechanisms by reducing cell death and promoting cell proliferation, and reducing pulmonary permeability.",2016 Mar 23,"['Toba, Hiroaki', 'Tomankova, Tereza', 'Wang, Yingchun', 'Bai, Xiaohui', 'Cho, Hae-Ra', 'Guan, Zhehong', 'Adeyi, Oyedele A.', 'Tian, Feng', 'Keshavjee, Shaf', 'Liu, Mingyao']",Oncotarget,,,False
2ebb6c8bf24d0955f26398dcc7653b0f6fb5c9f7,PMC,"Transgenic Mice Expressing MCP-1 by the Urothelium Demonstrate Bladder Hypersensitivity, Pelvic Pain and Voiding Dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study",http://dx.doi.org/10.1371/journal.pone.0163829,PMC5042429,27684718,CC BY,"Monocyte chemoattractant protein-1 (MCP-1) is one of the key chemokines that play important roles in diverse inflammatory and chronic pain conditions. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating inflammatory condition of the urinary bladder characterized by the hallmark symptoms of pelvic pain and voiding dysfunction. To facilitate IC/BPS research, we used transgenic technology to develop a novel urothelial MCP-1 secretion mouse model (URO-MCP-1). A transgene consisting of the uroplakin II gene promoter and the mouse MCP-1 coding sequence with a secretory element was constructed and microinjected. URO-MCP-1 mice were found to express MCP-1 mRNA in the bladder epithelium and MCP-1 protein in the urine, and developed bladder inflammation 24 hours after intravesical administration of a single sub-noxious dose of lipopolysaccharide (LPS). The inflamed bladders of URO-MCP-1 mice exhibited elevated mRNAs for interleukin (IL)-1ß, IL-6, substance P precursor, and nerve growth factor as well as increased macrophage infiltration. In parallel with these phenotypic changes, URO-MCP-1 mice manifested significant functional changes at days 1 and 3 after cystitis induction. These functional changes included pelvic pain as measured by von Frey filament stimulation and voiding dysfunction (increased urinary frequency, reduced average volume voided per micturition, and reduced maximum volume voided per micturition) as measured by micturition cages. Micturition changes remained evident at day 7 after cystitis induction, although these changes were not statistically significant. Control wild-type C57BL/6 mice manifested no clear changes in histological, biochemical and behavioral features after similar cystitis induction with LPS. Taken together, our results indicate that URO-MCP-1 mice are hypersensitive to bladder irritants such as LPS and develop pelvic pain and voiding dysfunction upon cystitis induction, providing a novel model for IC/BPS research.",2016 Sep 29,"['Xu, Suming', 'Wang, Xu', 'Wang, Yaoqin', 'Lutgendorf, Susan', 'Bradley, Catherine', 'Schrepf, Andrew', 'Kreder, Karl', ""O'Donnell, Michael"", 'Luo, Yi']",PLoS One,,,True
da215867201d36fa409a1f64aa89dfe75d537784,PMC,A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus,http://dx.doi.org/10.1371/journal.pntd.0004953,PMC5042537,27685649,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.",2016 Sep 29,"['Patel, Pranav', 'Abd El Wahed, Ahmed', 'Faye, Oumar', 'Prüger, Pauline', 'Kaiser, Marco', 'Thaloengsok, Sasikanya', 'Ubol, Sukathida', 'Sakuntabhai, Anavaj', 'Leparc-Goffart, Isabelle', 'Hufert, Frank T.', 'Sall, Amadou A.', 'Weidmann, Manfred', 'Niedrig, Matthias']",PLoS Negl Trop Dis,,,True
7d017d5285477ca084487a5fd8435fd64a59cce6,PMC,A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus,http://dx.doi.org/10.1371/journal.pntd.0004953,PMC5042537,27685649,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.",2016 Sep 29,"['Patel, Pranav', 'Abd El Wahed, Ahmed', 'Faye, Oumar', 'Prüger, Pauline', 'Kaiser, Marco', 'Thaloengsok, Sasikanya', 'Ubol, Sukathida', 'Sakuntabhai, Anavaj', 'Leparc-Goffart, Isabelle', 'Hufert, Frank T.', 'Sall, Amadou A.', 'Weidmann, Manfred', 'Niedrig, Matthias']",PLoS Negl Trop Dis,,,False
543059615137f6168bc68b4e7b5989f368a45a88,PMC,A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus,http://dx.doi.org/10.1371/journal.pntd.0004953,PMC5042537,27685649,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.",2016 Sep 29,"['Patel, Pranav', 'Abd El Wahed, Ahmed', 'Faye, Oumar', 'Prüger, Pauline', 'Kaiser, Marco', 'Thaloengsok, Sasikanya', 'Ubol, Sukathida', 'Sakuntabhai, Anavaj', 'Leparc-Goffart, Isabelle', 'Hufert, Frank T.', 'Sall, Amadou A.', 'Weidmann, Manfred', 'Niedrig, Matthias']",PLoS Negl Trop Dis,,,False
07567f87e6aace24f9146427f637ffba089ae28e,PMC,A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus,http://dx.doi.org/10.1371/journal.pntd.0004953,PMC5042537,27685649,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.",2016 Sep 29,"['Patel, Pranav', 'Abd El Wahed, Ahmed', 'Faye, Oumar', 'Prüger, Pauline', 'Kaiser, Marco', 'Thaloengsok, Sasikanya', 'Ubol, Sukathida', 'Sakuntabhai, Anavaj', 'Leparc-Goffart, Isabelle', 'Hufert, Frank T.', 'Sall, Amadou A.', 'Weidmann, Manfred', 'Niedrig, Matthias']",PLoS Negl Trop Dis,,,False
9a70adddbedf930be6c69a07b7c652240434f7ac,PMC,A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus,http://dx.doi.org/10.1371/journal.pntd.0004953,PMC5042537,27685649,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.",2016 Sep 29,"['Patel, Pranav', 'Abd El Wahed, Ahmed', 'Faye, Oumar', 'Prüger, Pauline', 'Kaiser, Marco', 'Thaloengsok, Sasikanya', 'Ubol, Sukathida', 'Sakuntabhai, Anavaj', 'Leparc-Goffart, Isabelle', 'Hufert, Frank T.', 'Sall, Amadou A.', 'Weidmann, Manfred', 'Niedrig, Matthias']",PLoS Negl Trop Dis,,,False
55c20a9eec895b673ce0751374bc9e725739101a,PMC,A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus,http://dx.doi.org/10.1371/journal.pntd.0004953,PMC5042537,27685649,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.",2016 Sep 29,"['Patel, Pranav', 'Abd El Wahed, Ahmed', 'Faye, Oumar', 'Prüger, Pauline', 'Kaiser, Marco', 'Thaloengsok, Sasikanya', 'Ubol, Sukathida', 'Sakuntabhai, Anavaj', 'Leparc-Goffart, Isabelle', 'Hufert, Frank T.', 'Sall, Amadou A.', 'Weidmann, Manfred', 'Niedrig, Matthias']",PLoS Negl Trop Dis,,,False
ca5f961909d1bf4d26815debd83d11f84b2c52d2,PMC,A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus,http://dx.doi.org/10.1371/journal.pntd.0004953,PMC5042537,27685649,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.",2016 Sep 29,"['Patel, Pranav', 'Abd El Wahed, Ahmed', 'Faye, Oumar', 'Prüger, Pauline', 'Kaiser, Marco', 'Thaloengsok, Sasikanya', 'Ubol, Sukathida', 'Sakuntabhai, Anavaj', 'Leparc-Goffart, Isabelle', 'Hufert, Frank T.', 'Sall, Amadou A.', 'Weidmann, Manfred', 'Niedrig, Matthias']",PLoS Negl Trop Dis,,,False
306ae95aab18fe16957a74a8681ed32130c052f4,PMC,A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus,http://dx.doi.org/10.1371/journal.pntd.0004953,PMC5042537,27685649,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.",2016 Sep 29,"['Patel, Pranav', 'Abd El Wahed, Ahmed', 'Faye, Oumar', 'Prüger, Pauline', 'Kaiser, Marco', 'Thaloengsok, Sasikanya', 'Ubol, Sukathida', 'Sakuntabhai, Anavaj', 'Leparc-Goffart, Isabelle', 'Hufert, Frank T.', 'Sall, Amadou A.', 'Weidmann, Manfred', 'Niedrig, Matthias']",PLoS Negl Trop Dis,,,False
5a6330a739f18fd6bc502bd9b59de55e8c081d4e,PMC,"ESICM LIVES 2016: part one: Milan, Italy. 1-5 October 2016",http://dx.doi.org/10.1186/s40635-016-0098-x,PMC5042924,,CC BY,,2016 Sep 29,"['Bos, L.', 'Schouten, L.', 'van Vught, L.', 'Wiewel, M.', 'Ong, D.', 'Cremer, O.', 'Artigas, A.', 'Martin-Loeches, I.', 'Hoogendijk, A.', 'van der Poll, T.', 'Horn, J.', 'Juffermans, N.', 'Schultz, M.', 'de Prost, N.', 'Pham, T.', 'Carteaux, G.', 'Dessap, A. Mekontso', 'Brun-Buisson, C.', 'Fan, E.', 'Bellani, G.', 'Laffey, J.', 'Mercat, A.', 'Brochard, L.', 'Maitre, B.', None, 'Howells, P. A.', 'Thickett, D. R.', 'Knox, C.', 'Park, D. P.', 'Gao, F.', 'Tucker, O.', 'Whitehouse, T.', 'McAuley, D. F.', 'Perkins, G. D.', 'Pham, T.', 'Laffey, J.', 'Bellani, G.', 'Fan, E.', None, 'Pisani, L.', 'Roozeman, J. P.', 'Simonis, F. D.', 'Giangregorio, A.', 'Schouten, L. R.', 'Van der Hoeven, S. M.', 'Horn, J.', 'Neto, A. Serpa', 'Festic, E.', 'Dondorp, A. M.', 'Grasso, S.', 'Bos, L. D.', 'Schultz, M. J.', 'Koster-Brouwer, M.', 'Verboom, D.', 'Scicluna, B.', 'van de Groep, K.', 'Frencken, J.', 'Schultz, M.', 'van der Poll, T.', 'Bonten, M.', 'Cremer, O.', 'Ko, J. I.', 'Kim, K. S.', 'Suh, G. J.', 'Kwon, W. Y.', 'Kim, K.', 'Shin, J. H.', 'Ranzani, O. T.', 'Prina, E.', 'Menendez, R.', 'Ceccato, A.', 'Mendez, R.', 'Cilloniz, C.', 'Gabarrus, A.', 'Ferrer, M.', 'Torres, A.', 'Urbano, A.', 'Zhang, L. A.', 'Swigon, D.', 'Pike, F.', 'Parker, R. S.', 'Clermont, G.', 'Scheer, C.', 'Kuhn, S. O.', 'Modler, A.', 'Vollmer, M.', 'Fuchs, C.', 'Hahnenkamp, K.', 'Rehberg, S.', 'Gründling, M.', 'Taggu, A.', 'Darang, N.', 'Öveges, N.', 'László, I.', 'Tánczos, K.', 'Németh, M.', 'Lebák, G.', 'Tudor, B.', 'Érces, D.', 'Kaszaki, J.', 'Huber, W.', 'Trásy, D.', 'Molnár, Z.', 'Ferrara, G.', 'Edul, V. S. Kanoore', 'Canales, H. S.', 'Martins, E.', 'Canullán, C.', 'Murias, G.', 'Pozo, M. O.', 'Eguillor, J. F. Caminos', 'Buscetti, M. G.', 'Ince, C.', 'Dubin, A.', 'Aya, H. D.', 'Rhodes, A.', 'Fletcher, N.', 'Grounds, R. M.', 'Cecconi, M.', 'Jacquet-Lagrèze, M.', 'Riche, M.', 'Schweizer, R.', 'Portran, P.', 'Fornier, W.', 'Lilot, M.', 'Neidecker, J.', 'Fellahi, J. L.', 'Escoresca-Ortega, A.', 'Gutiérrez-Pizarraya, A.', 'Charris-Castro, L.', 'Corcia-Palomo, Y.', 'Fernandez-Delgado, E.', 'Garnacho-Montero, J.', 'Roger, C.', 'Muller, L.', 'Elotmani, L.', 'Lipman, J.', 'Lefrant, J. Y.', 'Roberts, J. A.', 'Muñoz-Bermúdez, R.', 'Samper, M.', 'Climent, C.', 'Vasco, F.', 'Sara, V.', 'Luque, S.', 'Campillo, N.', 'Cerrato, S. Grau', 'Masclans, J. R.', 'Alvarez-Lerma, F.', 'Brugger, S. Carvalho', 'Jimenez, G. Jimenez', 'Torner, M. Miralbés', 'Cabello, J. Trujillano', 'Garrido, B. Balsera', 'Casals, X. Nuvials', 'Gaite, F. Barcenilla', 'Vidal, M. Vallverdú', 'Martínez, M. Palomar', 'Gusarov, V.', 'Shilkin, D.', 'Dementienko, M.', 'Nesterova, E.', 'Lashenkova, N.', 'Kuzovlev, A.', 'Zamyatin, M.', 'Demoule, A.', 'Carreira, S.', 'Lavault, S.', 'Palancca, O.', 'Morawiec, E.', 'Mayaux, J.', 'Arnulf, I.', 'Similowski, T.', 'Rasmussen, B. S.', 'Maltesen, R. G.', 'Hanifa, M.', 'Pedersen, S.', 'Kristensen, S. R.', 'Wimmer, R.', 'Panigada, M.', 'Bassi, G. Li', 'Ranzani, O. T.', 'Kolobow, T.', 'Zanella, A.', 'Cressoni, M.', 'Berra, L.', 'Parrini, V.', 'Kandil, H.', 'Salati, G.', 'Livigni, S.', 'Amatu, A.', 'Andreotti, A.', 'Tagliaferri, F.', 'Moise, G.', 'Mercurio, G.', 'Costa, A.', 'Vezzani, A.', 'Lindau, S.', 'Babel, J.', 'Cavana, M.', 'Consonni, D.', 'Pesenti, A.', 'Gattinoni, L.', 'Torres, A.', None, 'Mansouri, P.', 'Zand, F.', 'Zahed, L.', 'Dehghanrad, F.', 'Bahrani, M.', 'Ghorbani, M.', 'Cambiaghi, B.', 'Moerer, O.', 'Mauri, T.', 'Kunze-Szikszay, N.', 'Ritter, C.', 'Pesenti, A.', 'Quintel, M.', 'Vilander, L. M.', 'Kaunisto, M. A.', 'Vaara, S. T.', 'Pettilä, V.', None, 'Mulier, J. L. G. Haitsma', 'Rozemeijer, S.', 'Spoelstra-de Man, A. M. E.', 'Elbers, P. E.', 'Tuinman, P. R.', 'de Waard, M. C.', 'Oudemans-van Straaten, H. M.', 'Liberatore, A. M. A.', 'Souza, R. B.', 'Martins, A. M. C. R. P. F.', 'Vieira, J. C. F.', 'Koh, I. H. J.', 'Martínez, M. Galindo', 'Sánchez, R. Jiménez', 'Gascón, L. Martínez', 'Mulero, M. D. Rodríguez', 'Freire, A. Ortín', 'Muñoz, A. Ojados', 'Acebes, S. Rebollo', 'Martínez, Á. Fernández', 'Aliaga, S. Moreno', 'Para, L. Herrera', 'Payá, J. Murcia', 'Mulero, F. Rodríguez', 'Guerci, P.', 'Ince, Y.', 'Heeman, P.', 'Ergin, B.', 'Ince, C.', 'Uz, Z.', 'Massey, M.', 'Ince, Y.', 'Papatella, R.', 'Bulent, E.', 'Guerci, P.', 'Toraman, F.', 'Ince, C.', 'Longbottom, E. R.', 'Torrance, H. D.', 'Owen, H. C.', 'Hinds, C. J.', 'Pearse, R. M.', 'O’Dywer, M. J.', 'Trogrlic, Z.', 'van der Jagt, M.', 'Lingsma, H.', 'Ponssen, H. H.', 'Schoonderbeek, J. F.', 'Schreiner, F.', 'Verbrugge, S. J.', 'Duran, S.', 'van Achterberg, T.', 'Bakker, J.', 'Gommers, D. A. M. P. J.', 'Ista, E.', 'Krajčová, A.', 'Waldauf, P.', 'Duška, F.', 'Shah, A.', 'Roy, N.', 'McKechnie, S.', 'Doree, C.', 'Fisher, S.', 'Stanworth, S. J.', 'Jensen, J. F.', 'Overgaard, D.', 'Bestle, M. H.', 'Christensen, D. F.', 'Egerod, I.', None, 'Pivkina, A.', 'Gusarov, V.', 'Zhivotneva, I.', 'Pasko, N.', 'Zamyatin, M.', 'Jensen, J. F.', 'Egerod, I.', 'Bestle, M. H.', 'Christensen, D. F.', 'Alklit, A.', 'Hansen, R. L.', 'Knudsen, H.', 'Grode, L. B.', 'Overgaard, D.', None, 'Hravnak, M.', 'Chen, L.', 'Dubrawski, A.', 'Clermont, G.', 'Pinsky, M. R.', 'Parry, S. M.', 'Knight, L. D.', 'Connolly, B. C.', 'Baldwin, C. E.', 'Puthucheary, Z. A.', 'Denehy, L.', 'Hart, N.', 'Morris, P. E.', 'Mortimore, J.', 'Granger, C. L.', 'Jensen, H. I.', 'Piers, R.', 'Van den Bulcke, B.', 'Malmgren, J.', 'Metaxa, V.', 'Reyners, A. K.', 'Darmon, M.', 'Rusinova, K.', 'Talmor, D.', 'Meert, A. P.', 'Cancelliere, L.', 'Zubek, L.', 'Maia, P.', 'Michalsen, A.', 'Decruyenaere, J.', 'Kompanje, E.', 'Vanheule, S.', 'Azoulay, E.', 'Vansteelandt, S.', 'Benoit, D.', 'Van den Bulcke, B.', 'Piers, R.', 'Jensen, H. I.', 'Malmgren, J.', 'Metaxa, V.', 'Reyners, A. K.', 'Darmon, M.', 'Rusinova, K.', 'Talmor, D.', 'Meert, A. P.', 'Cancelliere, L.', 'Zubek, L.', 'Maia, P.', 'Michalsen, A.', 'Decruyenaere, J.', 'Kompanje, E.', 'Vanheule, S.', 'Azoulay, E.', 'Vansteelandt, S.', 'Benoit, D.', 'Ryan, C.', 'Dawson, D.', 'Ball, J.', 'Noone, K.', 'Aisling, B.', 'Prudden, S.', 'Ntantana, A.', 'Matamis, D.', 'Savvidou, S.', 'Giannakou, M.', 'Gouva, M.', 'Nakos, G.', 'Koulouras, V.', 'Aron, J.', 'Lumley, G.', 'Milliken, D.', 'Dhadwal, K.', 'McGrath, B. A.', 'Lynch, S. J.', 'Bovento, B.', 'Sharpe, G.', 'Grainger, E.', 'Pieri-Davies, S.', 'Wallace, S.', 'McGrath, B.', 'Lynch, S. J.', 'Bovento, B.', 'Grainger, E.', 'Pieri-Davies, S.', 'Sharpe, G.', 'Wallace, S.', 'Jung, M.', 'Cho, J.', 'Park, H.', 'Suh, G.', 'Kousha, O.', 'Paddle, J.', 'Gripenberg, L. Gamrin', 'Rehal, M. Sundström', 'Wernerman, J.', 'Rooyackers, O.', 'de Grooth, H. J.', 'Choo, W. P.', 'Spoelstra-de Man, A. M.', 'Swart, E. L.', 'Oudemans-van Straaten, H. M.', 'Talan, L.', 'Güven, G.', 'Altıntas, N. D.', 'Padar, M.', 'Uusvel, G.', 'Starkopf, L.', 'Starkopf, J.', 'Blaser, A. Reintam', 'Kalaiselvan, M. S.', 'Arunkumar, A. S.', 'Renuka, M. K.', 'Shivkumar, R. L.', 'Volbeda, M.', 'ten Kate, D.', 'Hoekstra, M.', 'van der Maaten, J. M.', 'Nijsten, M. W.', 'Komaromi, A.', 'Rooyackers, O.', 'Wernerman, J.', 'Norberg, Å.', 'Smedberg, M.', 'Mori, M.', 'Pettersson, L.', 'Norberg, Å.', 'Rooyackers, O.', 'Wernerman, J.', 'Theodorakopoulou, M.', 'Christodoulopoulou, T.', 'Diamantakis, A.', 'Frantzeskaki, F.', 'Kontogiorgi, M.', 'Chrysanthopoulou, E.', 'Lygnos, M.', 'Diakaki, C.', 'Armaganidis, A.', 'Gundogan, K.', 'Dogan, E.', 'Coskun, R.', 'Muhtaroglu, S.', 'Sungur, M.', 'Ziegler, T.', 'Guven, M.', 'Kleyman, A.', 'Khaliq, W.', 'Andreas, D.', 'Singer, M.', 'Meierhans, R.', 'Schuepbach, R.', 'De Brito-Ashurst, I.', 'Zand, F.', 'Sabetian, G.', 'Nikandish, R.', 'Hagar, F.', 'Masjedi, M.', 'Maghsudi, B.', 'Vazin, A.', 'Ghorbani, M.', 'Asadpour, E.', 'Kao, K. C.', 'Chiu, L. C.', 'Hung, C. Y.', 'Chang, C. H.', 'Li, S. H.', 'Hu, H. C.', 'El Maraghi, S.', 'Ali, M.', 'Rageb, D.', 'Helmy, M.', 'Marin-Corral, J.', 'Vilà, C.', 'Masclans, J. R.', 'Vàzquez, A.', 'Martín-Loeches, I.', 'Díaz, E.', 'Yébenes, J. C.', 'Rodriguez, A.', 'Álvarez-Lerma, F.', None, 'Varga, N.', 'Cortina-Gutiérrez, A.', 'Dono, L.', 'Martínez-Martínez, M.', 'Maldonado, C.', 'Papiol, E.', 'Pérez-Carrasco, M.', 'Ferrer, R.', 'Nweze, K.', 'Morton, B.', 'Welters, I.', 'Houard, M.', 'Voisin, B.', 'Ledoux, G.', 'Six, S.', 'Jaillette, E.', 'Nseir, S.', 'Romdhani, S.', 'Bouneb, R.', 'Loghmari, D.', 'Aicha, N. Ben', 'Ayachi, J.', 'Meddeb, K.', 'Chouchène, I.', 'Khedher, A.', 'Boussarsar, M.', 'Chan, K. S.', 'Yu, W. L.', 'Marin-Corral, J.', 'Vilà, C.', 'Masclans, J. R.', 'Nolla, J.', 'Vidaur, L.', 'Bonastre, J.', 'Suberbiola, B.', 'Guerrero, J. E.', 'Rodriguez, A.', None, 'Coll, N. Ramon', 'Jiménez, G. Jiménez', 'Brugger, S. Carvalho', 'Calero, J. Codina', 'Garrido, B. Balsera', 'García, M.', 'Martínez, M. Palomar', 'Vidal, M. Vallverdú', 'de la Torre, M. C.', 'Vendrell, E.', 'Palomera, E.', 'Güell, E.', 'Yébenes, J. C.', 'Serra-Prat, M.', 'Bermejo-Martín, J. F.', 'Almirall, J.', 'Tomas, E.', 'Escoval, A.', 'Froe, F.', 'Pereira, M. H. Vitoria', 'Velez, N.', 'Viegas, E.', 'Filipe, E.', 'Groves, C.', 'Reay, M.', 'Chiu, L. C.', 'Hu, H. C.', 'Hung, C. Y.', 'Chang, C. H.', 'Li, S. H.', 'Kao, K. C.', 'Ballin, A.', 'Facchin, F.', 'Sartori, G.', 'Zarantonello, F.', 'Campello, E.', 'Radu, C. M.', 'Rossi, S.', 'Ori, C.', 'Simioni, P.', 'Umei, N.', 'Shingo, I.', 'Santos, A. C.', 'Candeias, C.', 'Moniz, I.', 'Marçal, R.', 'e Silva, Z. Costa', 'Ribeiro, J. M.', 'Georger, J. F.', 'Ponthus, J. P.', 'Tchir, M.', 'Amilien, V.', 'Ayoub, M.', 'Barsam, E.', 'Martucci, G.', 'Panarello, G.', 'Tuzzolino, F.', 'Capitanio, G.', 'Ferrazza, V.', 'Carollo, T.', 'Giovanni, L.', 'Arcadipane, A.', 'Sánchez, M. López', 'González-Gay, M. A.', 'Díaz, F. J. Llorca', 'López, M. I. Rubio', 'Zogheib, E.', 'Villeret, L.', 'Nader, J.', 'Bernasinski, M.', 'Besserve, P.', 'Caus, T.', 'Dupont, H.', 'Morimont, P.', 'Habran, S.', 'Hubert, R.', 'Desaive, T.', 'Blaffart, F.', 'Janssen, N.', 'Guiot, J.', 'Pironet, A.', 'Dauby, P.', 'Lambermont, B.', 'Zarantonello, F.', 'Ballin, A.', 'Facchin, F.', 'Sartori, G.', 'Campello, E.', 'Pettenuzzo, T.', 'Citton, G.', 'Rossi, S.', 'Simioni, P.', 'Ori, C.', 'Kirakli, C.', 'Ediboglu, O.', 'Ataman, S.', 'Yarici, M.', 'Tuksavul, F.', 'Keating, S.', 'Gibson, A.', 'Gilles, M.', 'Dunn, M.', 'Price, G.', 'Young, N.', 'Remeta, P.', 'Bishop, P.', 'Zamora, M. D. Fernández', 'Muñoz-Bono, J.', 'Curiel-Balsera, E.', 'Aguilar-Alonso, E.', 'Hinojosa, R.', 'Gordillo-Brenes, A.', 'Arboleda-Sánchez, J. A.', None, 'Skorniakov, I.', 'Vikulova, D.', 'Whiteley, C.', 'Shaikh, O.', 'Jones, A.', 'Ostermann, M.', 'Forni, L.', 'Scott, M.', 'Sahatjian, J.', 'Linde-Zwirble, W.', 'Hansell, D.', 'Laoveeravat, P.', 'Srisawat, N.', 'Kongwibulwut, M.', 'Peerapornrattana, S.', 'Suwachittanont, N.', 'Wirotwan, T. O.', 'Chatkaew, P.', 'Saeyub, P.', 'Latthaprecha, K.', 'Tiranathanagul, K.', 'Eiam-ong, S.', 'Kellum, J. A.', 'Berthelsen, R. E.', 'Perner, A.', 'Jensen, A. E. K.', 'Jensen, J. U.', 'Bestle, M. H.', 'Gebhard, D. J.', 'Price, J.', 'Kennedy, C. E.', 'Akcan-Arikan, A.', 'Liberatore, A. M. A.', 'Souza, R. B.', 'Martins, A. M. C. R. P. F.', 'Vieira, J. C. F.', 'Kang, Y. R.', 'Nakamae, M. N.', 'Koh, I. H. J.', 'Hamed, K.', 'Khaled, M. M.', 'Soliman, R. Aly', 'Mokhtar, M. Sherif', 'Seller-Pérez, G.', 'Arias-Verdú, D.', 'Llopar-Valdor, E.', 'De-Diós-Chacón, I.', 'Quesada-García, G.', 'Herrera-Gutierrez, M. E.', 'Hafes, R.', 'Carroll, G.', 'Doherty, P.', 'Wright, C.', 'Vera, I. G. Guerra', 'Ralston, M.', 'Gemmell, M. L.', 'MacKay, A.', 'Black, E.', 'Wright, C.', 'Docking, R. I.', 'Appleton, R.', 'Ralston, M. R.', 'Gemmell, L.', 'Appleton, R.', 'Wright, C.', 'Docking, R. I.', 'Black, E.', 'Mackay, A.', 'Rozemeijer, S.', 'Mulier, J. L. G. Haitsma', 'Röttgering, J. G.', 'Elbers, P. W. G.', 'Spoelstra-de Man, A. M. E.', 'Tuinman, P. R.', 'de Waard, M. C.', 'Oudemans-van Straaten, H. M.', 'Mejeni, N.', 'Nsiala, J.', 'Kilembe, A.', 'Akilimali, P.', 'Thomas, G.', 'Egerod, I.', 'Andersson, A. E.', 'Fagerdahl, A. M.', 'Knudsen, V.', None, 'Meddeb, K.', 'Cheikh, A. Ben', 'Hamdaoui, Y.', 'Ayachi, J.', 'Guiga, A.', 'Fraj, N.', 'Romdhani, S.', 'Sma, N.', 'Bouneb, R.', 'Chouchene, I.', 'Khedher, A.', 'Bouafia, N.', 'Boussarsar, M.', 'Amirian, A.', 'Ziaian, B.', 'Masjedi, M.', 'Fleischmann, C.', 'Thomas-Rueddel, D. O.', 'Schettler, A.', 'Schwarzkopf, D.', 'Stacke, A.', 'Reinhart, K.', 'Filipe, E.', 'Escoval, A.', 'Martins, A.', 'Sousa, P.', 'Velez, N.', 'Viegas, E.', 'Tomas, E.', 'Snell, G.', 'Matsa, R.', 'Paary, T. T. S.', 'Kalaiselvan, M. S.', 'Cavalheiro, A. M.', 'Rocha, L. L.', 'Vallone, C. S.', 'Tonilo, A.', 'Lobato, M. D. S.', 'Malheiro, D. T.', 'Sussumo, G.', 'Lucino, N. M.', 'Zand, F.', 'Rosenthal, V. D.', 'Masjedi, M.', 'Sabetian, G.', 'Maghsudi, B.', 'Ghorbani, M.', 'Dashti, A. Sanaei', 'Yousefipour, A.', 'Goodall, J. R.', 'Williamson, M.', 'Tant, E.', 'Thomas, N.', 'Balci, C.', 'Gonen, C.', 'Haftacı, E.', 'Gurarda, H.', 'Karaca, E.', 'Paldusová, B.', 'Zýková, I.', 'Šímová, D.', 'Houston, S.', 'D’Antona, L.', 'Lloyd, J.', 'Garnelo-Rey, V.', 'Sosic, M.', 'Sotosek-Tokmazic, V.', 'Kuharic, J.', 'Antoncic, I.', 'Dunatov, S.', 'Sustic, A.', 'Chong, C. T.', 'Sim, M.', 'Lyovarin, T.', 'Díaz, F. M. Acosta', 'Galdó, S. Narbona', 'Garach, M. Muñoz', 'Romero, O. Moreno', 'Bailón, A. M. Pérez', 'Pinel, A. Carranza', 'Colmenero, M.', 'Gritsan, A.', 'Gazenkampf, A.', 'Korchagin, E.', 'Dovbish, N.', 'Lee, R. M.', 'Lim, M. P. P.', 'Chong, C. T.', 'Lim, B. C. L.', 'See, J. J.', 'Assis, R.', 'Filipe, F.', 'Lopes, N.', 'Pessoa, L.', 'Pereira, T.', 'Catorze, N.', 'Aydogan, M. S.', 'Aldasoro, C.', 'Marchio, P.', 'Jorda, A.', 'Mauricio, M. D.', 'Guerra-Ojeda, S.', 'Gimeno-Raga, M.', 'Colque-Cano, M.', 'Bertomeu-Artecero, A.', 'Aldasoro, M.', 'Valles, S. L.', 'Tonon, D.', 'Triglia, T.', 'Martin, J. C.', 'Alessi, M. C.', 'Bruder, N.', 'Garrigue, P.', 'Velly, L.', 'Spina, S.', 'Scaravilli, V.', 'Marzorati, C.', 'Colombo, E.', 'Savo, D.', 'Vargiolu, A.', 'Cavenaghi, G.', 'Citerio, G.', 'Andrade, A. H. V.', 'Bulgarelli, P.', 'Araujo, J. A. P.', 'Gonzalez, V.', 'Souza, V. A.', 'Costa, A.', 'Massant, C.', 'Filho, C. A. C. Abreu', 'Morbeck, R. A.', 'Burgo, L. E.', 'van Groenendael, R.', 'van Eijk, L. T.', 'Leijte, G. P.', 'Koeneman, B.', 'Kox, M.', 'Pickkers, P.', 'García-de la Torre, A.', 'de la Torre-Prados, M.', 'Fernández-Porcel, A.', 'Rueda-Molina, C.', 'Nuevo-Ortega, P.', 'Tsvetanova-Spasova, T.', 'Cámara-Sola, E.', 'García-Alcántara, A.', 'Salido-Díaz, L.', 'Liao, X.', 'Feng, T.', 'Zhang, J.', 'Cao, X.', 'Wu, Q.', 'Xie, Z.', 'Li, H.', 'Kang, Y.', 'Winkler, M. S.', 'Nierhaus, A.', 'Mudersbach, E.', 'Bauer, A.', 'Robbe, L.', 'Zahrte, C.', 'Schwedhelm, E.', 'Kluge, S.', 'Zöllner, C.', 'Morton, B.', 'Mitsi, E.', 'Pennington, S. H.', 'Reine, J.', 'Wright, A. D.', 'Parker, R.', 'Welters, I. D.', 'Blakey, J. D.', 'Rajam, G.', 'Ades, E. W.', 'Ferreira, D. M.', 'Wang, D.', 'Kadioglu, A.', 'Gordon, S. B.', 'Koch, R.', 'Kox, M.', 'Rahamat-Langedoen, J.', 'Schloesser, J.', 'de Jonge, M.', 'Pickkers, P.', 'Bringue, J.', 'Guillamat-Prats, R.', 'Torrents, E.', 'Martinez, M. L.', 'Camprubí-Rimblas, M.', 'Artigas, A.', 'Blanch, L.', 'Park, S. Y.', 'Park, Y. B.', 'Song, D. K.', 'Shrestha, S.', 'Park, S. H.', 'Koh, Y.', 'Park, M. J.', 'Hong, C. W.', 'Lesur, O.', 'Coquerel, D.', 'Sainsily, X.', 'Cote, J.', 'Söllradl, T.', 'Murza, A.', 'Dumont, L.', 'Dumaine, R.', 'Grandbois, M.', 'Sarret, P.', 'Marsault, E.', 'Salvail, D.', 'Auger-Messier, M.', 'Chagnon, F.', None, 'Lauretta, M. P.', 'Greco, E.', 'Dyson, A.', 'Singer, M.', 'Preau, S.', 'Ambler, M.', 'Sigurta, A.', 'Saeed, S.', 'Singer, M.', 'Sarıca, L. Topcu', 'Zibandeh, N.', 'Genc, D.', 'Gul, F.', 'Akkoc, T.', 'Kombak, E.', 'Cinel, L.', 'Akkoc, T.', 'Cinel, I.', 'Pollen, S. J.', 'Arulkumaran, N.', 'Singer, M.', 'Torrance, H. D.', 'Longbottom, E. R.', 'Warnes, G.', 'Hinds, C. J.', 'Pennington, D. J.', 'Brohi, K.', 'O’Dwyer, M. J.', 'Kim, H. Y.', 'Na, S.', 'Kim, J.', 'Chang, Y. F.', 'Chao, A.', 'Shih, P. Y.', 'Lee, C. T.', 'Yeh, Y. C.', 'Chen, L. W.', 'Adriaanse, M.', 'Trogrlic, Z.', 'Ista, E.', 'Lingsma, H.', 'Rietdijk, W.', 'Ponssen, H. H.', 'Schoonderbeek, J. F.', 'Schreiner, F.', 'Verbrugge, S. J.', 'Duran, S.', 'Gommers, D. A. M. P. J.', 'van der Jagt, M.', 'Funcke, S.', 'Sauerlaender, S.', 'Saugel, B.', 'Pinnschmidt, H.', 'Reuter, D. A.', 'Nitzschke, R.', 'Perbet, S.', 'Biboulet, C.', 'Lenoire, A.', 'Bourdeaux, D.', 'Pereira, B.', 'Plaud, B.', 'Bazin, J. E.', 'Sautou, V.', 'Mebazaa, A.', 'Constantin, J. M.', 'Legrand, M.', 'Boyko, Y.', 'Jennum, P.', 'Nikolic, M.', 'Oerding, H.', 'Holst, R.', 'Toft, P.', 'Nedergaard, H. K.', 'Haberlandt, T.', 'Jensen, H. I.', 'Toft, P.', 'Park, S.', 'Kim, S.', 'Cho, Y. J.', 'Lim, Y. J.', 'Chan, A.', 'Tang, S.', 'Nunes, S. L.', 'Forsberg, S.', 'Blomqvist, H.', 'Berggren, L.', 'Sörberg, M.', 'Sarapohja, T.', 'Wickerts, C. J.', 'Hofhuis, J. G. M.', 'Rose, L.', 'Blackwood, B.', 'Akerman, E.', 'Mcgaughey, J.', 'Egerod, I.', 'Fossum, M.', 'Foss, H.', 'Georgiou, E.', 'Graff, H. J.', 'Kalafati, M.', 'Sperlinga, R.', 'Schafer, A.', 'Wojnicka, A. G.', 'Spronk, P. E.', 'Zand, F.', 'Khalili, F.', 'Afshari, R.', 'Sabetian, G.', 'Masjedi, M.', 'Maghsudi, B.', 'Khodaei, H. Haddad', 'Javadpour, S.', 'Petramfar, P.', 'Nasimi, S.', 'Vazin, A.', 'Ziaian, B.', 'Tabei, H.', 'Gunther, A.', 'Hansen, J. O.', 'Sackey, P.', 'Storm, H.', 'Bernhardsson, J.', 'Sundin, Ø.', 'Bjärtå, A.', 'Bienert, A.', 'Smuszkiewicz, P.', 'Wiczling, P.', 'Przybylowski, K.', 'Borsuk, A.', 'Trojanowska, I.', 'Matysiak, J.', 'Kokot, Z.', 'Paterska, M.', 'Grzeskowiak, E.', 'Messina, A.', 'Bonicolini, E.', 'Colombo, D.', 'Moro, G.', 'Romagnoli, S.', 'De Gaudio, A. R.', 'Corte, F. Della', 'Romano, S. M.', 'Silversides, J. A.', 'Major, E.', 'Mann, E. E.', 'Ferguson, A. J.', 'Mcauley, D. F.', 'Marshall, J. C.', 'Blackwood, B.', 'Fan, E.', 'Diaz-Rodriguez, J. A.', 'Silva-Medina, R.', 'Gomez-Sandoval, E.', 'Gomez-Gonzalez, N.', 'Soriano-Orozco, R.', 'Gonzalez-Carrillo, P. L.', 'Hernández-Flores, M.', 'Pilarczyk, K.', 'Lubarksi, J.', 'Wendt, D.', 'Dusse, F.', 'Günter, J.', 'Huschens, B.', 'Demircioglu, E.', 'Jakob, H.', 'Palmaccio, A.', 'Dell’Anna, A. M.', 'Grieco, D. L.', 'Torrini, F.', 'Iaquaniello, C.', 'Bongiovanni, F.', 'Antonelli, M.', 'Toscani, L.', 'Antonakaki, D.', 'Bastoni, D.', 'Aya, H. D.', 'Rhodes, A.', 'Cecconi, M.', 'Jozwiak, M.', 'Depret, F.', 'Teboul, J. L.', 'Alphonsine, J.', 'Lai, C.', 'Richard, C.', 'Monnet, X.', 'László, I.', 'Demeter, G.', 'Öveges, N.', 'Tánczos, K.', 'Németh, M.', 'Trásy, D.', 'Kertmegi, I.', 'Érces, D.', 'Tudor, B.', 'Kaszaki, J.', 'Molnár, Z.', 'Hasanin, A.', 'Lotfy, A.', 'El-adawy, A.', 'Nassar, H.', 'Mahmoud, S.', 'Abougabal, A.', 'Mukhtar, A.', 'Quinty, F.', 'Habchi, S.', 'Luzi, A.', 'Antok, E.', 'Hernandez, G.', 'Lara, B.', 'Enberg, L.', 'Ortega, M.', 'Leon, P.', 'Kripper, C.', 'Aguilera, P.', 'Kattan, E.', 'Bakker, J.', 'Huber, W.', 'Lehmann, M.', 'Sakka, S.', 'Bein, B.', 'Schmid, R. M.', 'Preti, J.', 'Creteur, J.', 'Herpain, A.', 'Marc, J.', 'Zogheib, E.', 'Trojette, F.', 'Bar, S.', 'Kontar, L.', 'Titeca, D.', 'Richecoeur, J.', 'Gelee, B.', 'Verrier, N.', 'Mercier, R.', 'Lorne, E.', 'Maizel, J.', 'Dupont, H.', 'Slama, M.', 'Abdelfattah, M. E.', 'Eladawy, A.', 'Elsayed, M. A. Ali', 'Mukhtar, A.', 'Montenegro, A. Pedraza', 'Zepeda, E. Monares', 'Granillo, J. Franco', 'Sánchez, J. S. Aguirre', 'Alejo, G. Camarena', 'Cabrera, A. Rugerio', 'Montoya, A. A. Tanaka', 'Lee, C.', 'Hatib, F.', 'Cannesson, M.', 'Theerawit, P.', 'Morasert, T.', 'Sutherasan, Y.', 'Zani, G.', 'Mescolini, S.', 'Diamanti, M.', 'Righetti, R.', 'Scaramuzza, A.', 'Papetti, M.', 'Terenzoni, M.', 'Gecele, C.', 'Fusari, M.', 'Hakim, K. A.', 'Chaari, A.', 'Ismail, M.', 'Elsaka, A. H.', 'Mahmoud, T. M.', 'Bousselmi, K.', 'Kauts, V.', 'Casey, W. F.', 'Hutchings, S. D.', 'Naumann, D.', 'Wendon, J.', 'Watts, S.', 'Kirkman, E.', 'Jian, Z.', 'Buddi, S.', 'Lee, C.', 'Settels, J.', 'Hatib, F.', 'Pinsky, M. R.', 'Bertini, P.', 'Guarracino, F.', 'Trepte, C.', 'Richter, P.', 'Haas, S. A.', 'Eichhorn, V.', 'Kubitz, J. C.', 'Reuter, D. A.', 'Soliman, M. S.', 'Hamimy, W. I.', 'Fouad, A. Z.', 'Mukhtar, A. M.', 'Charlton, M.', 'Tonks, L.', 'Mclelland, L.', 'Coats, T. J.', 'Thompson, J. P.', 'Sims, M. R.', 'Williams, D.', 'Roushdy, D. Z.', 'Soliman, R. A.', 'Nahas, R. A.', 'Arafa, M. Y.', 'Hung, W. T.', 'Chiang, C. C.', 'Huang, W. C.', 'Lin, K. C.', 'Lin, S. C.', 'Cheng, C. C.', 'Kang, P. L.', 'Wann, S. R.', 'Mar, G. Y.', 'Liu, C. P.', 'Carranza, M. Lopez', 'Fernandez, H. Sancho', 'Roman, J. A. Sanchez', 'Lucena, F.', 'Garcia, A. Campanario', 'Vazquez, A. Loza', 'Serrano, A. Lesmes', None, 'Moreira, L. Sayagues', 'Vidal-Perez, R.', 'Herranz, U. Anido', 'Acuna, J. M. Garcia', 'Gil, C. Pena', 'Allut, J. L. Garcia', 'Sedes, P. Rascado', 'Lopez, C. Martin', 'Paz, E. Saborido', 'Rodriguez, C. Galban', 'Gonzalez-Juanatey, J. R.', 'Vallejo-Baez, A.', 'de la Torre-Prados, M. V.', 'Nuevo-Ortega, P.', 'Fernández-Porcel, A.', 'Cámara-Sola, E.', 'Tsvetanova-Spasova, T.', 'Rueda-Molina, C.', 'Salido-Díaz, L.', 'García-Alcántara, A.', None, 'Aron, J.', 'Marharaj, R.', 'Gervasio, K.', 'Bottiroli, M.', 'Mondino, M.', 'De Caria, D.', 'Calini, A.', 'Montrasio, E.', 'Milazzo, F.', 'Gagliardone, M. P.', 'Vallejo-Báez, A.', 'de la Torre-Prados, M. V.', 'Nuevo-Ortega, P.', 'Fernández-Porcel, A.', 'Cámara-Sola, E.', 'Tsvetanova-Spasova, T.', 'Rueda-Molina, C.', 'Salido-Díaz, L.', 'García-Alcántara, A.', None, 'Moreira, L. Sayagues', 'Vidal-Perez, R.', 'Anido, U.', 'Gil, C. Pena', 'Acuna, J. M. Garcia', 'Sedes, P. Rascado', 'Lopez, C. Martin', 'Paz, E. Saborido', 'Allut, J. L. Garcia', 'Rodriguez, C. Galban', 'Gonzalez-Juanatey, J. R.', 'Hamdaoui, Y.', 'Khedher, A.', 'Cheikh-Bouhlel, M.', 'Ayachi, J.', 'Meddeb, K.', 'Sma, N.', 'Fraj, N.', 'Aicha, N. Ben', 'Romdhani, S.', 'Bouneb, R.', 'Chouchene, I.', 'Boussarsar, M.', 'Dela Cruz, M. P. R. D. L.', 'Bernardo, J. M.', 'Galfo, F.', 'Dyson, A.', 'Singer, M.', 'Marino, A.', 'Dyson, A.', 'Singer, M.', 'Chao, C. C.', 'Hou, P.', 'Huang, W. C.', 'Hung, C. C.', 'Chiang, C. H.', 'Hung, W. T.', 'Lin, K. C.', 'Lin, S. C.', 'Liou, Y. J.', 'Hung, S. M.', 'Lin, Y. S.', 'Cheng, C. C.', 'Kuo, F. Y.', 'Chiou, K. R.', 'Chen, C. J.', 'Yan, L. S.', 'Liu, C. Y.', 'Wang, H. H.', 'Kang, P. L.', 'Chen, H. L.', 'Ho, C. K.', 'Mar, G. Y.', 'Liu, C. P.', 'Grewal, S.', 'Gopal, S.', 'Corbett, C.', 'Wilson, A.', 'Capps, J.', 'Ayoub, W.', 'Lomas, A.', 'Ghani, S.', 'Moore, J.', 'Atkinson, D.', 'Sharman, M.', 'Swinnen, W.', 'Pauwels, J.', 'Mignolet, K.', 'Pannier, E.', 'Koch, A.', 'Sarens, T.', 'Temmerman, W.', 'Elmenshawy, A. M.', 'Fayed, A. M.', 'Elboriuny, M.', 'Hamdy, E.', 'Zakaria, E.', 'Falk, A. C.', 'Petosic, A.', 'Olafsen, K.', 'Wøien, H.', 'Flaatten, H.', 'Sunde, K.', 'Agra, J. J. Cáceres', 'Cabrera, J. L. Santana', 'Santana, J. D. Martín', 'Alzola, L. Melián', 'Pérez, H. Rodríguez', 'Pires, T. Castro', 'Calderón, H.', 'Pereira, A.', 'Castro, S.', 'Granja, C.', 'Norkiene, I.', 'Urbanaviciute, I.', 'Kezyte, G.', 'Ringaitiene, D.', 'Jovaisa, T.', 'Vogel, G.', 'Johansson, U. B.', 'Sandgren, A.', 'Svensen, C.', 'Joelsson-Alm, E.', 'Leite, M. A.', 'Murbach, L. D.', 'Osaku, E. F.', 'Costa, C. R. L. M.', 'Pelenz, M.', 'Neitzke, N. M.', 'Moraes, M. M.', 'Jaskowiak, J. L.', 'Silva, M. M. M.', 'Zaponi, R. S.', 'Abentroth, L. R. L.', 'Ogasawara, S. M.', 'Jorge, A. C.', 'Duarte, P. A. D.', 'Murbach, L. D.', 'Leite, M. A.', 'Osaku, E. F.', 'Barreto, J.', 'Duarte, S. T.', 'Taba, S.', 'Miglioranza, D.', 'Gund, D. P.', 'Lordani, C. F.', 'Costa, C. R. L. M.', 'Ogasawara, S. M.', 'Jorge, A. C.', 'Duarte, P. A. D.', 'Vollmer, H.', 'Gager, M.', 'Waldmann, C.', 'Mazzeo, A. T.', 'Tesio, R.', 'Filippini, C.', 'Vallero, M. E.', 'Giolitti, C.', 'Caccia, S.', 'Medugno, M.', 'Tenaglia, T.', 'Rosato, R.', 'Mastromauro, I.', 'Brazzi, L.', 'Terragni, P. P.', 'Urbino, R.', 'Fanelli, V.', 'Ranieri, V. M.', 'Mascia, L.', 'Ballantyne, J.', 'Paton, L.', 'Mackay, A.', 'Perez-Teran, P.', 'Roca, O.', 'Ruiz-Rodriguez, J. C.', 'Zapatero, A.', 'Serra, J.', 'Masclans, J. R.', 'Bianzina, S.', 'Cornara, P.', 'Rodi, G.', 'Tavazzi, G.', 'Pozzi, M.', 'Iotti, G. A.', 'Mojoli, F.', 'Braschi, A.', 'Vishnu, A.', 'Buche, D.', 'Pande, R.', 'Moolenaar, D. L. J.', 'Bakhshi-Raiez, F.', 'Dongelmans, D. A.', 'de Keizer, N. F.', 'de Lange, D. W.', 'Fernández, I. Fuentes', 'Baño, D. Martínez', 'Moreno, J. L. Buendía', 'Rubio, R. Jara', 'Scott, J.', 'Phelan, D.', 'Morely, D.', 'O’Flynn, J.', 'Stapleton, P.', 'Lynch, M.', 'Marsh, B.', 'Carton, E.', 'O’Loughlin, C.', 'Cheng, K. C.', 'Sung, M. I.', 'Elghonemi, M. O.', 'Saleh, M. H.', 'Meyhoff, T. S.', 'Krag, M.', 'Hjortrup, P. B.', 'Perner, A.', 'Møller, M. H.', 'Öhman, T.', 'Sigmundsson, T.', 'Redondo, E.', 'Hallbäck, M.', 'Suarez-Sipmann, F.', 'Björne, H.', 'Sander, C. Hällsjö', None, 'Cressoni, M.', 'Chiumello, D.', 'Chiurazzi, C.', 'Brioni, M.', 'Algieri, I.', 'Guanziroli, M.', 'Vergani, G.', 'Tonetti, T.', 'Tomic, I.', 'Colombo, A.', 'Crimella, F.', 'Carlesso, E.', 'Colombo, A.', 'Gasparovic, V.', 'Gattinoni, L.', 'El-Sherif, R.', 'Al-Basser, M. Abd', 'Raafat, A.', 'El-Sherif, A.', 'Simonis, F. D.', 'Schouten, L. R. A.', 'Cremer, O. L.', 'Ong, D. S. Y.', 'Amoruso, G.', 'Cinnella, G.', 'Schultz, M. J.', 'Bos, L. D. J.', 'Huber, W.', 'Schmidle, P.', 'Findeisen, M.', 'Hoppmann, P.', 'Jaitner, J.', 'Brettner, F.', 'Schmid, R. M.', 'Lahmer, T.', None, 'Festic, E.', 'Rajagopalan, G.', 'Bansal, V.', 'Frank, R.', 'Hinds, R.', 'Levitt, J.', None, 'Siddiqui, S.', None, 'Gilbert, J. P.', 'Sim, K.', 'Wang, C. H.', 'Hu, H. C.', 'Li, I. J.', 'Tang, W. R.', 'Kao, K. C.', 'Persona, P.', 'De Cassai, A.', 'Franco, M.', 'Facchin, F.', 'Ori, C.', 'Rossi, S.', 'Goffi, A.', 'Li, S. H.', 'Hu, H. C.', 'Chiu, L. C.', 'Hung, C. Y.', 'Chang, C. H.', 'Kao, K. C.', 'Ruiz, B. Llorente', 'Varas, J. Lujan', 'Montero, R. Molina', 'Delgado, C. Pintado', 'Navarrete, O.', 'Mezquita, M. Vazquez', 'Peces, E. Alonso', 'Nakamura, M. A. M.', 'Hajjar, L. A.', 'Galas, F. R. B. G.', 'Ortiz, T. A.', 'Amato, M. B. P.', 'Bitker, L.', 'Costes, N.', 'Le Bars, D.', 'Lavenne, F.', 'Mojgan, D.', 'Richard, J. C.', 'Chiurazzi, C.', 'Cressoni, M.', 'Massari, D.', 'Guanziroli, M.', 'Vergani, G.', 'Gotti, M.', 'Brioni, M.', 'Algieri, I.', 'Cadringher, P.', 'Tonetti, T.', 'Chiumello, D.', 'Gattinoni, L.', 'Zerman, A.', 'Türkoğlu, M.', 'Arık, G.', 'Yıldırım, F.', 'Güllü, Z.', 'Kara, I.', 'Boyacı, N.', 'Aydoğan, B. Basarık', 'Gaygısız, Ü.', 'Gönderen, K.', 'Aygencel, G.', 'Aydoğdu, M.', 'Ülger, Z.', 'Gürsel, G.', 'Riera, J.', 'Toral, C. Maldonado', 'Mazo, C.', 'Martínez, M.', 'Baldirà, J.', 'Lagunes, L.', 'Roman, A.', 'Deu, M.', 'Rello, J.', 'Levine, D. J.', 'Mohus, R. M.', 'Askim, Å.', 'Paulsen, J.', 'Mehl, A.', 'Dewan, A. T.', 'Damås, J. K.', 'Solligård, E.', 'Åsvold, B. O.', None, 'Paulsen, J.', 'Askim, Å.', 'Mohus, R. M.', 'Mehl, A.', 'DeWan, A.', 'Solligård, E.', 'Damås, J. K.', 'Åsvold, B. O.', 'Aktepe, O.', 'Kara, A.', 'Yeter, H.', 'Topeli, A.', 'Norrenberg, M.', 'Devroey, M.', 'Khader, H.', 'Preiser, J. C.', 'Tang, Z.', 'Qiu, C.', 'Tong, L.', 'Cai, C.', 'Theodorakopoulou, M.', 'Diamantakis, A.', 'Kontogiorgi, M.', 'Chrysanthopoulou, E.', 'Christodoulopoulou, T.', 'Frantzeskaki, F.', 'Lygnos, M.', 'Apostolopoulou, O.', 'Armaganidis, A.', 'Moon, J. Y.', 'Park, M. R.', 'Kwon, I. S.', 'Chon, G. R.', 'Ahn, J. Y.', 'Kwon, S. J.', 'Chang, Y. J.', 'Lee, J. Y.', 'Yoon, S. Y.', 'Lee, J. W.', None, 'Kostalas, M.', 'Mckinlay, J.', 'Kooner, G.', 'Dudas, G.', 'Horton, A.', 'Kerr, C.', 'Karanjia, N.', 'Creagh-Brown, B.', 'Altintas, N. D.', 'Izdes, S.', 'Keremoglu, O.', 'Alkan, A.', 'Neselioglu, S.', 'Erel, O.', 'Tardif, N.', 'Gustafsson, T.', 'Rooyackers, O.', 'MacEachern, K. N.', 'Traille, M.', 'Bromberg, I.', 'Lapinsky, S. E.', 'Moore, M. J.', 'Tang, Z.', 'Cai, C.', 'Tong, L.', 'García-Garmendia, J. L.', 'Villarrasa-Clemente, F.', 'Maroto-Monserrat, F.', 'Rufo-Tejeiro, O.', 'Jorge-Amigo, V.', 'Sánchez-Santamaría, M.', 'Colón-Pallarés, C.', 'Barrero-Almodóvar, A.', 'Gallego-Lara, S.', 'Anthon, C. T.', 'Müller, R. B.', 'Haase, N.', 'Møller, K.', 'Hjortrup, P. B.', 'Wetterslev, J.', 'Perner, A.', 'Nakanishi, M.', 'Kuriyama, A.', 'Fukuoka, T.', 'Abd el Halim, M. A.', 'Elsaid hafez, M. H.', 'Moktar, A. M.', 'Eladawy, A.', 'Elazizy, H. M.', 'Hakim, K. Abdel', 'Chaari, A.', 'Elbahr, M.', 'Ismail, M.', 'Mahmoud, T.', 'Kauts, V.', 'Bousselmi, K.', 'Khalil, E.', 'Casey, W.', 'Zaky, S. H.', 'Rizk, A.', 'Elghonemi, M. O.', 'Ahmed, R.', 'Vieira, J. C. F.', 'Souza, R. B.', 'Liberatore, A. M. A.', 'Koh, I. H. J.', 'Ospina-Tascón, G. A.', 'Marin, A. F. Garcia', 'Echeverry, G. J.', 'Bermudez, W. F.', 'Madriñan-Navia, H. J.', 'Valencia, J. D.', 'Quiñonez, E.', 'Marulanda, A.', 'Arango-Dávila, C. A.', 'Bruhn, A.', 'Hernandez, G.', 'De Backer, D.', 'Cortes, D. Orbegozo', 'Su, F.', 'Vincent, J. L.', 'Creteur, J.', 'Tullo, L.', 'Mirabella, L.', 'Di Molfetta, P.', 'Cinnella, G.', 'Dambrosio, M.', 'Lujan, C. Villavicencio', 'irigoyen, J. Leache', 'Cartanya ferré, M.', 'García, R. Carbonell', 'Mukhtar, A.', 'Ahmed, M.', 'El Ayashi, M.', 'Hasanin, A.', 'Ayman, E.', 'Salem, M.', 'Eladawy, A.', 'Fathy, S.', 'Nassar, H.', 'Zaghlol, A.', 'Arzapalo, M. F. Aguilar', 'Valsø, Å.', 'Sunde, K.', 'Rustøen, T.', 'Schou-Bredal, I.', 'Skogstad, L.', 'Tøien, K.', 'Padilla, C.', 'Palmeiro, Y.', 'Egbaria, W.', 'Kigli, R.', 'Maertens, B.', 'Blot, K.', 'Blot, S.', 'Santana-Santos, E.', 'dos Santos, E. R.', 'Ferretti-Rebustini, R. E. D. L.', 'dos Santos, R. D. C. C. D. O.', 'Verardino, R. G. S.', 'Bortolotto, L. A.', 'Doyle, A. M.', 'Naldrett, I.', 'Tillman, J.', 'Price, S.', 'Shrestha, S.', 'Pearson, P.', 'Greaves, J.', 'Goodall, D.', 'Berry, A.', 'Richardson, A.', 'Odundo, G. O.', 'Omengo, P.', 'Obonyo, P.', 'Chanzu, N. M.', 'Kleinpell, R.', 'Sarris, S. J.', 'Nedved, P.', 'Heitschmidt, M.', 'Ben-Ghezala, H.', 'Snouda, S.', 'Djobbi, S.', 'Ben-Ghezala, H.', 'Snouda, S.', 'Rose, L.', 'Adhikari, N. K. J.', 'Leasa, D.', 'Fergusson, D.', 'Mckim, D. A.', 'Weblin, J.', 'Tucker, O.', 'McWilliams, D.', 'Doesburg, F.', 'Cnossen, F.', 'Dieperink, W.', 'Bult, W.', 'Nijsten, M. W. N.', 'Galvez-Blanco, G. A.', 'Zepeda, E. Monares', 'Guzman, C. I. Olvera', 'Sánchez, J. S. Aguirre', 'Granillo, J. Franco', 'Stroud, J. Santos', 'Thomson, R.', 'Llaurado-Serra, M.', 'Lobo-Civico, A.', 'Pi-Guerrero, M.', 'Blanco-Sanchez, I.', 'Piñol-Tena, A.', 'Paños-Espinosa, C.', 'Alabart-Segura, Y.', 'Coloma-Gomez, B.', 'Fernandez-Blanco, A.', 'Braga-Dias, F.', 'Treso-Geira, M.', 'Valeiras-Valero, A.', 'Martinez-Reyes, L.', 'Sandiumenge, A.', 'Jimenez-Herrera, M. F.', None, 'Prada, R.', 'Juárez, P.', 'Argandoña, R.', 'Díaz, J. J.', 'Ramirez, C. Sánchez', 'Saavedra, P.', 'Santana, S. Ruiz', 'Obukhova, O.', 'Kashiya, S.', 'Kurmukov, I. A.', 'Pronina, A. M.', 'Simeone, P.', 'Puybasset, L.', 'Auzias, G.', 'Coulon, O.', 'Lesimple, B.', 'Torkomian, G.', 'Velly, L.', 'Bienert, A.', 'Bartkowska-Sniatkowska, A.', 'Wiczling, P.', 'Szerkus, O.', 'Siluk, D.', 'Bartkowiak-Wieczorek, J.', 'Rosada-Kurasinska, J.', 'Warzybok, J.', 'Borsuk, A.', 'Kaliszan, R.', 'Grzeskowiak, E.', 'Caballero, C. Hernandez', 'Roberts, S.', 'Isgro, G.', 'Hall, D.', 'Guillaume, G.', 'Passouant, O.', 'Dumas, F.', 'Bougouin, W.', 'Champigneulle, B.', 'Arnaout, M.', 'Chelly, J.', 'Chiche, J. D.', 'Varenne, O.', 'Mira, J. P.', 'Marijon, E.', 'Cariou, A.', 'Beerepoot, M.', 'Touw, H. R.', 'Parlevliet, K.', 'Boer, C.', 'Elbers, P. W.', 'Tuinman, P. R.', 'Reina, Á. J. Roldán', 'Palomo, Y. Corcia', 'Bermúdez, R. Martín', 'Villén, L. Martín', 'García, I. Palacios', 'Izurieta, J. R. Naranjo', 'Bernal, J. B. Pérez', 'Jiménez, F. J. Jiménez', None, 'Cota-Delgado, F.', 'de la Torre-Prados, M. V.', 'Fernández-Porcel, A.', 'Nuevo-Ortega, P.', 'Cámara-Sola, E.', 'Tsvetanova-Spasova, T.', 'Rueda-Molina, C.', 'Salido-Díaz, L.', 'García-Alcántara, A.', 'Kaneko, T.', 'Tanaka, H.', 'Kamikawa, M.', 'Karashima, R.', 'Iwashita, S.', 'Irie, H.', 'Kasaoka, S.', 'Arola, O.', 'Laitio, R.', 'Saraste, A.', 'Airaksinen, J.', 'Pietilä, M.', 'Hynninen, M.', 'Wennervirta, J.', 'Bäcklund, M.', 'Ylikoski, E.', 'Silvasti, P.', 'Nukarinen, E.', 'Grönlund, J.', 'Harjola, V. P.', 'Niiranen, J.', 'Korpi, K.', 'Varpula, M.', 'Roine, R. O.', 'Laitio, T.', None, 'Salah, S.', 'Hassen, B. G.', 'Fehmi, A. Mohamed', 'Kim, S.', 'Hsu, Y. C.', 'Barea-Mendoza, J.', 'García-Fuentes, C.', 'Castillo-Jaramillo, M.', 'Dominguez-Aguado, H.', 'Viejo-Moreno, R.', 'Terceros-Almanza, L.', 'Aznárez, S. Bermejo', 'Mudarra-Reche, C.', 'Xu, W.', 'Chico-Fernández, M.', 'Montejo-González, J. C.', 'Crewdson, K.', 'Thomas, M.', 'Merghani, M.', 'Fenner, L.', 'Morgan, P.', 'Lockey, D.', 'van Lieshout, E. J.', 'Oomen, B.', 'Binnekade, J. M.', 'Dongelmans, D. A.', 'de Haan, R. J.', 'Juffermans, N. P.', 'Vroom, M. B.', 'Algarte, R.', 'Martínez, L.', 'Sánchez, B.', 'Romero, I.', 'Martínez, F.', 'Quintana, S.', 'Trenado, J.', 'Sheikh, O.', 'Pogson, D.', 'Clinton, R.', 'Riccio, F.', 'Gemmell, L.', 'MacKay, A.', 'Arthur, A.', 'Young, L.', 'Sinclair, A.', 'Markopoulou, D.', 'Venetsanou, K.', 'Filippou, L.', 'Salla, E.', 'Stratouli, S.', 'Alamanos, I.', 'Guirgis, A. H.', 'Rodriguez, R. Gutiérrez', 'Lorente, M. J. Furones', 'Guarasa, I. Macias', 'Ukere, A.', 'Meisner, S.', 'Greiwe, G.', 'Opitz, B.', 'Benten, D.', 'Nashan, B.', 'Fischer, L.', 'Trepte, C. J. C.', 'Reuter, D. A.', 'Haas, S. A.', 'Behem, C. R.', 'Tavazzi, G.', 'Ana, B.', 'Vazir, A.', 'Gibson, D.', 'Price, S.', 'Masjedi, M.', 'Hadavi, M. R.', 'alam, M. Riahi', 'Sasani, M. R.', 'Parenti, N.', 'Agrusta, F.', 'Palazzi, C.', 'Pifferi, B.', 'Sganzerla, R.', 'Tagliazucchi, F.', 'Luciani, A.', 'Möller, M.', 'Müller-Engelmann, J.', 'Montag, G.', 'Adams, P.', 'Lange, C.', 'Neuzner, J.', 'Gradaus, R.', 'Wodack, K. H.', 'Thürk, F.', 'Waldmann, A. D.', 'Grässler, M. F.', 'Nishimoto, S.', 'Böhm, S. H.', 'Kaniusas, E.', 'Reuter, D. A.', 'Trepte, C. J.', 'Sigmundsson, T.', 'Öhman, T.', 'Redondo, E.', 'Hallbäck, M.', 'Wallin, M.', 'Sipman, F. Suarez', 'Oldner, A.', 'Sander, C. Hällsjö', 'Björne, H.', 'Colinas, L.', 'Hernandez, G.', 'Vicho, R.', 'Serna, M.', 'Cuena, R.', 'Canabal, A.', None, 'Chaari, A.', 'Hakim, K. Abdel', 'Etman, M.', 'El Bahr, M.', 'El Sakka, A.', 'Bousselmi, K.', 'Arali, A.', 'Kauts, V.', 'Casey, W. F.', 'Bond, O.', 'De Santis, P.', 'Iesu, E.', 'Franchi, F.', 'Vincent, J. L.', 'Creteur, J.', 'Scolletta, S.', 'Taccone, F. S.', 'Marutyan, Z.', 'Hamidova, L.', 'Shakotko, A.', 'Movsisyan, V.', 'Uysupova, I.', 'Evdokimov, A.', 'Petrikov, S.', 'Gonen, C.', 'Haftacı, E.', 'Balci, C.', 'Calvo, F. J. Redondo', 'Bejarano, N.', 'Baladron, V.', 'Villazala, R.', 'Redondo, J.', 'Padilla, D.', 'Villarejo, P.', 'Akcan-Arikan, A.', 'Kennedy, C. E.', 'Arzapalo, M. F. Aguilar', 'Gomez-Gonzalez, C.', 'Mas-Font, S.', 'Puppo-Moreno, A.', 'Herrera-Gutierrez, M.', 'Garcia-Garcia, M.', 'Aldunate-Calvo, S.', None, 'Plata-Menchaca, E. P.', 'Pérez-Fernández, X. L.', 'Estruch, M.', 'Betbese-Roig, A.', 'Campos, P. Cárdenas', 'Lora, M. Rojas', 'Gaibor, N. D. Toapanta', 'Medina, R. S. Contreras', 'Sanguino, V. D. Gumucio', 'Casanova, E. J.', 'Riera, J. Sabater', None, 'Kritmetapak, K.', 'Peerapornratana, S.', 'Kittiskulnam, P.', 'Dissayabutra, T.', 'Tiranathanagul, K.', 'Susantithapong, P.', 'Praditpornsilpa, K.', 'Tungsanga, K.', 'Eiam-Ong, S.', 'Srisawat, N.', 'Winkelmann, T.', 'Busch, T.', 'Meixensberger, J.', 'Bercker, S.', 'Cabeza, E. M. Flores', 'Sánchez, M. Sánchez', 'Giménez, N. Cáceres', 'Melón, C. Gutierrez', 'de Lucas, E. Herrero', 'Estañ, P. Millán', 'Bernal, M. Hernández', 'de Lorenzo y Mateos, A. Garcia', 'Ergin, B.', 'Guerci, P.', 'Specht, P. A. C.', 'Ince, Y.', 'Ince, C.', 'Balik, M.', 'Zakharchenko, M.', 'Los, F.', 'Brodska, H.', 'de Tymowski, C.', 'Augustin, P.', 'Desmard, M.', 'Montravers, P.', 'Stapel, S. N.', 'de Boer, R.', 'Oudemans, H. M.', 'Hollinger, A.', 'Schweingruber, T.', 'Jockers, F.', 'Dickenmann, M.', 'Siegemund, M.', None, 'Runciman, N.', 'Ralston, M.', 'Appleton, R.', 'Mauri, T.', 'Alban, L.', 'Turrini, C.', 'Sasso, T.', 'Langer, T.', 'Panigada, M.', 'Taccone, P.', 'Carlesso, E.', 'Marenghi, C.', 'Grasselli, G.', 'Pesenti, A.', 'Wibart, P.', 'Reginault, T.', 'Garcia, M.', 'Barbrel, B.', 'Benard, A.', 'Bader, C.', 'Vargas, F.', 'Bui, H. N.', 'Hilbert, G.', 'Simón, J. M. Serrano', 'Sánchez, P. Carmona', 'Ferrón, F. Ruiz', 'de Acilu, M. García', 'Marin, J.', 'Antonia, V.', 'Ruano, L.', 'Monica, M.', 'Ferrer, R.', 'Masclans, J. R.', 'Roca, O.', 'Hong, G.', 'Kim, D. H.', 'Kim, Y. S.', 'Park, J. S.', 'Jee, Y. K.', 'xiang, Z. Yu', 'Jia-xing, W.', 'dan, W. Xiao', 'long, N. Wen', 'Yu, W.', 'Yan, Z.', 'Cheng, X.', 'Kobayashi, T.', 'Onodera, Y.', 'Akimoto, R.', 'Sugiura, A.', 'Suzuki, H.', 'Iwabuchi, M.', 'Nakane, M.', 'Kawamae, K.', 'Sanchez, P. Carmona', 'Rodriguez, M. D. Bautista', 'Delgado, M. Rodriguez', 'Sánchez, V. Martínez de Pinillos', 'Gómez, A. Mula', 'Simón, J. M. Serrano', 'Beuret, P.', 'Fortes, C.', 'Lauer, M.', 'Reboul, M.', 'Chakarian, J. C.', 'Fabre, X.', 'Philippon-Jouve, B.', 'Devillez, S.', 'Clerc, M.', 'Rittayamai, N.', 'Sklar, M.', 'Dres, M.', 'Rauseo, M.', 'Campbell, C.', 'West, B.', 'Tullis, D. E.', 'Brochard, L.', 'Onodera, Y.', 'Akimoto, R.', 'Suzuki, H.', 'Okada, M.', 'Nakane, M.', 'Kawamae, K.', 'Ahmad, N.', 'Wood, M.', 'Glossop, A.', 'Lucas, J. Higuera', 'Ortiz, A. Blandino', 'Alonso, D. Cabestrero', 'De Pablo Sánchez, R.', 'González, L. Rey', 'Costa, R.', 'Spinazzola, G.', 'Pizza, A.', 'Ferrone, G.', 'Rossi, M.', 'Antonelli, M.', 'Conti, G.', 'Ribeiro, H.', 'Alves, J.', 'Sousa, M.', 'Reis, P.', 'Socolovsky, C. S.', 'Cauley, R. P.', 'Frankel, J. E.', 'Beam, A. L.', 'Olaniran, K. O.', 'Gibbons, F. K.', 'Christopher, K. B.', 'Pennington, J.', 'Zolfaghari, P.', 'King, H. S.', 'Kong, H. H. Y.', 'Shum, H. P.', 'Yan, W. W.', 'Kaymak, C.', 'Okumus, N.', 'Sari, A.', 'Erdogdu, B.', 'Aksun, S.', 'Basar, H.', 'Ozcan, A.', 'Ozcan, N.', 'Oztuna, D.', 'Malmgren, J. A.', 'Lundin, S.', 'Torén, K.', 'Eckerström, M.', 'Wallin, A.', 'Waldenström, A. C.', None, 'Riccio, F. C.', 'Pogson, D.', 'Antonio, A. C. P.', 'Leivas, A. F.', 'Kenji, F.', 'James, E.', 'Morgan, P.', 'Carroll, G.', 'Gemmell, L.', 'MacKay, A.', 'Wright, C.', 'Ballantyne, J.', 'Jonnada, S.', 'Gerrard, C. S.', 'Jones, N.', 'Salciccioli, J. D.', 'Marshall, D. C.', 'Komorowski, M.', 'Hartley, A.', 'Sykes, M. C.', 'Goodson, R.', 'Shalhoub, J.', 'Villanueva, J. R. Fernández', 'Garda, R. Fernández', 'Lago, A. M. López', 'Ruiz, E. Rodríguez', 'Vaquero, R. Hernández', 'Rodríguez, C. Galbán', 'Pérez, E. Varo', 'Hilasque, C.', 'Oliva, I.', 'Sirgo, G.', 'Martin, M. C.', 'Olona, M.', 'Gilavert, M. C.', 'Bodí, M.', 'Ebm, C.', 'Aggarwal, G.', 'Huddart, S.', 'Quiney, N.', 'Cecconi, M.', 'Fernandes, S. M.', 'Silva, J. Santos', 'Gouveia, J.', 'Silva, D.', 'Marques, R.', 'Bento, H.', 'Alvarez, A.', 'Silva, Z. Costa', 'Diaz, D. Díaz', 'Martínez, M. Villanova', 'Herrejon, E. Palencia', 'de la Gandara, A. Martinez', 'Gonzalo, G.', 'Lopez, M. A.', 'de Gopegui Miguelena, P. Ruíz', 'Matilla, C. I. Bernal', 'Chueca, P. Sánchez', 'Longares, M. D. C. Rodríguez', 'Abril, R. Ramos', 'Aguilar, A. L. Ruíz', 'de Murillas, R. Garrido López', 'Fernández, R. Fernández', 'Laborías, P. Morales', 'Castellanos, M. A. Díaz', 'Laborías, M. E. Morales', 'Cho, J.', 'Kim, J.', 'Park, J.', 'Woo, S.', 'West, T.', 'Powell, E.', 'Rimmer, A.', 'Orford, C.', 'Jones, N.', 'Williams, J.', 'Matilla, C. I. Bernal', 'de Gopegui Miguelena, P. Ruiz', 'Chueca, P. Sánchez', 'Abril, R. Ramos', 'Longares, M. D. C. Rodríguez', 'Aguilar, A. L. Ruíz', 'de Murillas, R. Garrido López', 'Bourne, R. S.', 'Shulman, R.', 'Tomlin, M.', 'Mills, G. H.', 'Borthwick, M.', 'Berry, W.', 'Huertas, D. García', 'Manzano, F.', 'Villagrán-Ramírez, F.', 'Ruiz-Perea, A.', 'Rodríguez-Mejías, C.', 'Santiago-Ruiz, F.', 'Colmenero-Ruiz, M.', 'König, C.', 'Matt, B.', 'Kortgen, A.', 'Hartog, C. S.', 'Wong, A.', 'Balan, C.', 'Barker, G.', 'Srisawat, N.', 'Peerapornratana, S.', 'Laoveeravat, P.', 'Tachaboon, S.', 'Eiam-ong, S.', 'Paratz, J.', 'Kayambu, G.', 'Boots, R.', 'Arzapalo, M. F. Aguilar', 'Vlasenko, R.', 'Gromova, E.', 'Loginov, S.', 'Kiselevskiy, M.', 'Dolgikova, Y.', 'Tang, K. B.', 'Chau, C. M.', 'Lam, K. N.', 'Gil, E.', 'Suh, G. Y.', 'Park, C. M.', 'Park, J.', 'Chung, C. R.', 'Lee, C. T.', 'Chao, A.', 'Shih, P. Y.', 'Chang, Y. F.', 'Lai, C. H.', 'Hsu, Y. C.', 'Yeh, Y. C.', 'Cheng, Y. J.', 'Colella, V.', 'Zarrillo, N.', 'D’Amico, M.', 'Forfori, F.', 'Pezza, B.', 'Laddomada, T.', 'Beltramelli, V.', 'Pizzaballa, M. L.', 'Doronzio, A.', 'Balicco, B.', 'Kiers, D.', 'van der Heijden, W.', 'Gerretsen, J.', 'de Mast, Q.', 'el Messaoudi, S.', 'Rongen, G.', 'Gomes, M.', 'Kox, M.', 'Pickkers, P.', 'Riksen, N. P.', 'Kashiwagi, Y.', 'Okada, M.', 'Hayashi, K.', 'Inagaki, Y.', 'Fujita, S.', 'Nakamae, M. N.', 'Kang, Y. R.', 'Souza, R. B.', 'Liberatore, A. M. A.', 'Koh, I. H. J.', 'Blet, A.', 'Sadoune, M.', 'Lemarié, J.', 'Bihry, N.', 'Bern, R.', 'Polidano, E.', 'Merval, R.', 'Launay, J. M.', 'Lévy, B.', 'Samuel, J. L.', 'Mebazaa, A.', 'Hartmann, J.', 'Harm, S.', 'Weber, V.']",Intensive Care Med Exp,,,True
c6b416e31cb51e4ecc6264f20bb37db28e9a4cef,PMC,Human IFIT1 Inhibits mRNA Translation of Rubulaviruses but Not Other Members of the Paramyxoviridae Family,http://dx.doi.org/10.1128/JVI.01056-16,PMC5044818,27512068,CC BY,"We have previously shown that IFIT1 is primarily responsible for the antiviral action of interferon (IFN) alpha/beta against parainfluenza virus type 5 (PIV5), selectively inhibiting the translation of PIV5 mRNAs. Here we report that while PIV2, PIV5, and mumps virus (MuV) are sensitive to IFIT1, nonrubulavirus members of the paramyxoviridae such as PIV3, Sendai virus (SeV), and canine distemper virus (CDV) are resistant. The IFIT1 sensitivity of PIV5 was not rescued by coinfection with an IFIT1-resistant virus (PIV3), demonstrating that PIV3 does not specifically inhibit the antiviral activity of IFIT1 and that the inhibition of PIV5 mRNAs is regulated by cis-acting elements. We developed an in vitro translation system using purified human IFIT1 to further investigate the mechanism of action of IFIT1. While the translations of PIV2, PIV5, and MuV mRNAs were directly inhibited by IFIT1, the translations of PIV3, SeV, and CDV mRNAs were not. Using purified human mRNA-capping enzymes, we show biochemically that efficient inhibition by IFIT1 is dependent upon a 5′ guanosine nucleoside cap (which need not be N7 methylated) and that this sensitivity is partly abrogated by 2′O methylation of the cap 1 ribose. Intriguingly, PIV5 M mRNA, in contrast to NP mRNA, remained sensitive to inhibition by IFIT1 following in vitro 2′O methylation, suggesting that other structural features of mRNAs may influence their sensitivity to IFIT1. Thus, surprisingly, the viral polymerases (which have 2′-O-methyltransferase activity) of rubulaviruses do not protect these viruses from inhibition by IFIT1. Possible biological consequences of this are discussed. IMPORTANCE Paramyxoviruses cause a wide variety of diseases, and yet most of their genes encode structural proteins and proteins involved in their replication cycle. Thus, the amount of genetic information that determines the type of disease that paramyxoviruses cause is relatively small. One factor that will influence disease outcomes is how they interact with innate host cell defenses, including the interferon (IFN) system. Here we show that different paramyxoviruses interact in distinct ways with cells in a preexisting IFN-induced antiviral state. Strikingly, all the rubulaviruses tested were sensitive to the antiviral action of ISG56/IFIT1, while all the other paramyxoviruses tested were resistant. We developed novel in vitro biochemical assays to investigate the mechanism of action of IFIT1, demonstrating that the mRNAs of rubulaviruses can be directly inhibited by IFIT1 and that this is at least partially because their mRNAs are not correctly methylated.",2016 Sep 29,"['Young, D. F.', 'Andrejeva, J.', 'Li, X.', 'Inesta-Vaquera, F.', 'Dong, C.', 'Cowling, V. H.', 'Goodbourn, S.', 'Randall, R. E.']",J Virol,,,True
a374cb0eaeb9e3cf7b9e3d4f08ff21907437c159,PMC,Characterization of Two Monoclonal Antibodies That Recognize Linker Region and Carboxyl Terminal Domain of Coronavirus Nucleocapsid Protein,http://dx.doi.org/10.1371/journal.pone.0163920,PMC5045181,27689694,CC BY,"The transmissible gastroenteritis virus (TGEV) nucleocapsid (N) protein plays important roles in the replication and translation of viral RNA. The present study provides the first description of two monoclonal antibodies (mAbs) (5E8 and 3D7) directed against the TGEV N protein linker region (LKR) and carboxyl terminal domain (CTD). The mAbs 5E8 and 3D7 reacted with native N protein in western blotting and immunofluorescence assay (IFA). Two linear epitopes, (189)SVEQAVLAALKKLG(202) and (246)VTRFYGARSSSA(257), located in the LKR and CTD of TGEV N protein, respectively, were identified after truncating the protein and applying a peptide scanning technique. Using mAb 5E8, we observed that the N protein was expressed in the cytoplasm during TGEV replication and that the protein could be immunoprecipitated from TGEV-infected PK-15 cells. The mAb 5E8 can be applied for different approaches to diagnosis of TGEV infection. In addition, the antibodies represent useful tools for investigating the antigenic properties of the N protein.",2016 Sep 30,"['Zhang, Xin', 'Zhao, Xin', 'Dong, Hui', 'Zhu, Yunnuan', 'Shi, Hongyan', 'Chen, Jianfei', 'Shi, Da', 'Feng, Li']",PLoS One,,,True
7902a01d7b2422e17f964afa1ecf05ec1e3088e7,PMC,"Awareness of droplet and airborne isolation precautions among  dental health professionals during the outbreak of corona  virus infection in Riyadh city, Saudi Arabia",http://dx.doi.org/10.4317/jced.52811,PMC5045684,27703605,CC BY,"BACKGROUND: This study aimed to determine knowledge, attitude and practice of airborne and droplet isolation precautions among Dental Health Professionals (DHPs) (dental students, interns, practitioners and auxiliaries) during the outbreak of MERS (Middle East Respiratory Syndrome), corona virus infection in Riyadh city, Saudi Arabia. MATERIAL AND METHODS: A cross-sectional survey was conducted among 406 dental health professionals (DHPs) working in selected dental facilities in Riyadh city, Saudi Arabia during the outbreak of MERS (April-June 2013). A structured, close-ended, self-administered questionnaire explored the knowledge, attitude, and practice towards droplet and isolation precautions. Collected data was subjected to descriptive statistics to express demographic information, mean knowledge score, mean attitude score and practice score of DHPs. Inferential statistics (Mann-Whitney U test and Kruskal Wallis tests, p < 0.05) were used to examine differences between study variables. Spearman’s rho correlation was used to identify the association between the knowledge-attitude, knowledge-practice, and attitude-practice. RESULTS: A response rate of rate of 90.22% (406 out of 452) was obtained. The mean scores of knowledge, attitude and practice were 10.61 ± 1.19, 50.54 ± 7.53 and 8.50 ± 2.14 respectively. Spearman’s correlation test revealed a significant linear positive correlation between knowledge and attitude (r-0.501, P- 0.01), knowledge and practice (r-0.185, P-0.01) and attitude and practice (r-0.351, P- 0.01) of DHPs about airborne isolation precautions. CONCLUSIONS: Dental health professionals considered in the present study showed good knowledge, positive attitude and good practice towards droplet and airborne isolation precautions during outbreak of MERS. Key words:Knowledge, attitude, practice, droplet, airborne, precaution, dental professionals.",2016 Oct 1,"['Baseer, Mohammad-Abdul', 'Ansari, Shahzeb-Hasan', 'AlShamrani, Sultan-Saleh', 'Alakras, Abdul-Rahman', 'Mahrous, Raif', 'Alenazi, Abdul-Majeed']",J Clin Exp Dent,,,True
6e6fb58bc0253b1c8326599159f321be8a37736f,PMC,Integrating one health in national health policies of developing countries: India’s lost opportunities,http://dx.doi.org/10.1186/s40249-016-0181-2,PMC5047123,27716352,CC BY,"BACKGROUND: Globally, the threat of infectious diseases, particularly emerging infectious diseases, originating at the human-animal-environment interface, has caught health systems off guard. With forecasts that future pathogen emergence will be centred in hotspots in Asia, Africa, and Latin America, the need to prepare policy frameworks that can combat this threat is urgent. DISCUSSION: Emergence of diseases such as avian influenza and Ebola virus disease, which threatened social disruption, have established the need for intersectoral coordination/collaboration. These events led to the initiation of establishing institutionalised collaborative frameworks in India to adopt a One Health approach to disease prevention and control. However, the gains made in influenza control could not be adapted to other infectious diseases. Intersectoral coordination was briefly carried out, more as a reactive response to threats. The systemic failure to sustain such efforts have therefore, only undermined a coordinated response. The recent draft National Health Policy, 2015, has also failed to establish the need for intersectoral coordination in disease control approaches. Neglecting the need to endorse linkages between human health, animal health and husbandry, agriculture, and environmental sectors, has led to duplicative and weak response systems. The absence of health impact assessment with respect to the development agenda in policies, has cast negative effects on the health and wellbeing of man, animal, and the environment. Lack of attention to building core capacity in these critical sectors has further raised challenges in designing and deploying mitigation strategies. With developing countries like India being home to a major portion of the world’s poorest livestock farmers, the absence of a policy discourse that endorses the One Health approach in development and health policies is a major hurdle in eliminating poverty and poverty-related diseases. CONCLUSIONS: The adoption of One Health approaches in health and related sectoral policies is a critical policy requirement for India and other developing countries. The goal should be to not just establish preparedness plans, but also to encourage a policy environment where assessment and mitigation of downstream impacts of different agenda are incorporated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0181-2) contains supplementary material, which is available to authorized users.",2016 Oct 3,"['Chatterjee, Pranab', 'Kakkar, Manish', 'Chaturvedi, Sanjay']",Infect Dis Poverty,,,True
f6e7d1aaef6479469705a2ae0ea9a5e5a5e18abf,PMC,Immunoregulatory functions of immune complexes in vaccine and therapy,http://dx.doi.org/10.15252/emmm.201606593,PMC5048363,27572622,CC BY,"Clinical and experimental preparations of IgG/soluble antigen complexes, as well as those formed following antibody therapy in vivo, are multifaceted immune regulators. These immune complexes (ICs) have been tested in humans and animal models, mostly in forms of experimental or clinical vaccination, for at least a century. With intensified research on Fcγ receptor‐mediated immune modulation, as well as with immune complex‐directed antigen processing, presentation, and inflammatory responses, there are renewed interests of using ICs in vaccines and immunotherapies. Currently, IC‐based immune therapy has been broadly experimented in HBV and HIV viral infection control and antitumor treatments. However, mechanistic insights of IC‐based treatments are relatively recent subjects of study; strong efforts are needed to establish links to connect laboratory findings with clinical practices. This review covers the history, mechanisms, and in vivo outcomes of this safe and effective therapeutic tool, with a clear aim to bridge laboratory findings with evolving clinical applications.",2016 Oct 29,"['Wen, Yu‐mei', 'Mu, Libing', 'Shi, Yan']",EMBO Mol Med,,,True
de8f4493515bdf7ed934509024d19a66dc57016f,PMC,"Factors associated with clinical outcome in 25 patients with avian influenza A (H7N9) infection in Guangzhou, China",http://dx.doi.org/10.1186/s12879-016-1840-4,PMC5048464,27716101,CC BY,"BACKGROUND: Guangzhou reported its first laboratory-confirmed case of influenza A (H7N9) on January 10, 2014. A total of 25 cases were reported from the first wave of the epidemic until April 8, 2014. The fatality rate was much higher than in previous reports. The objective of the current work was to describe the clinical and epidemiological characteristics of A (H7N9) patients in Guangzhou and explore possible reasons for the high fatality rate. METHODS: Clinical and epidemiological information regarding A (H7N9) cases in Guangzhou was collected through review of medical records and field research. Data regarding clinical and laboratory features, treatment, and outcomes were extracted. RESULTS: Of the 25 patients, 84 % (21/25) had one or more underlying diseases. Fifteen patients (60.0 %) developed moderate to severe acute respiratory distress syndrome (ARDS), and 14 (56 %) died of the ARDS or multiorgan failure. Patients with longer delay between onset of illness and initiation of oseltamivir treatment were more likely to develop ARDS. Elevated C-creative protein, aspartate aminotransferase, creatine kinase, and lymphocytopenia predicted a higher risk of developing ARDS. CONCLUSIONS: The presence of underlying diseases and clinical complications predicted poor clinical outcome. Early oseltamivir treatment was associated with a reduced risk of developing ARDS.",2016 Oct 3,"['Wang, Hui', 'Xiao, XinCai', 'Lu, Jianyun', 'Chen, Zongqiu', 'Li, Kuibiao', 'Liu, Hui', 'Luo, Lei', 'Wang, Ming', 'Yang, ZhiCong']",BMC Infect Dis,,,True
18421f153f74c6b0f8f9efe88c2aad6b70547b99,PMC,Dissecting the Effect of Genetic Variation on the Hepatic Expression of Drug Disposition Genes across the Collaborative Cross Mouse Strains,http://dx.doi.org/10.3389/fgene.2016.00172,PMC5050206,27761138,CC BY,"A central challenge in pharmaceutical research is to investigate genetic variation in response to drugs. The Collaborative Cross (CC) mouse reference population is a promising model for pharmacogenomic studies because of its large amount of genetic variation, genetic reproducibility, and dense recombination sites. While the CC lines are phenotypically diverse, their genetic diversity in drug disposition processes, such as detoxification reactions, is still largely uncharacterized. Here we systematically measured RNA-sequencing expression profiles from livers of 29 CC lines under baseline conditions. We then leveraged a reference collection of metabolic biotransformation pathways to map potential relations between drugs and their underlying expression quantitative trait loci (eQTLs). By applying this approach on proximal eQTLs, including eQTLs acting on the overall expression of genes and on the expression of particular transcript isoforms, we were able to construct the organization of hepatic eQTL-drug connectivity across the CC population. The analysis revealed a substantial impact of genetic variation acting on drug biotransformation, allowed mapping of potential joint genetic effects in the context of individual drugs, and demonstrated crosstalk between drug metabolism and lipid metabolism. Our findings provide a resource for investigating drug disposition in the CC strains, and offer a new paradigm for integrating biotransformation reactions to corresponding variations in DNA sequences.",2016 Oct 5,"['Nachshon, Aharon', 'Abu-Toamih Atamni, Hanifa J.', 'Steuerman, Yael', ""Sheikh-Hamed, Roa'a"", 'Dorman, Alexandra', 'Mott, Richard', 'Dohm, Juliane C.', 'Lehrach, Hans', 'Sultan, Marc', 'Shamir, Ron', 'Sauer, Sascha', 'Himmelbauer, Heinz', 'Iraqi, Fuad A.', 'Gat-Viks, Irit']",Front Genet,,,True
7072f43043b3cbcaffc357902409ece63bc6f828,PMC,Next-Generation High-Throughput Functional Annotation of Microbial Genomes,http://dx.doi.org/10.1128/mBio.01245-16,PMC5050336,27703071,CC BY,"Host infection by microbial pathogens cues global changes in microbial and host cell biology that facilitate microbial replication and disease. The complete maps of thousands of bacterial and viral genomes have recently been defined; however, the rate at which physiological or biochemical functions have been assigned to genes has greatly lagged. The National Institute of Allergy and Infectious Diseases (NIAID) addressed this gap by creating functional genomics centers dedicated to developing high-throughput approaches to assign gene function. These centers require broad-based and collaborative research programs to generate and integrate diverse data to achieve a comprehensive understanding of microbial pathogenesis. High-throughput functional genomics can lead to new therapeutics and better understanding of the next generation of emerging pathogens by rapidly defining new general mechanisms by which organisms cause disease and replicate in host tissues and by facilitating the rate at which functional data reach the scientific community.",2016 Oct 4,"['Baric, Ralph S.', 'Crosson, Sean', 'Damania, Blossom', 'Miller, Samuel I.', 'Rubin, Eric J.']",mBio,,,True
04a0ec4b6cb5eeb0d2cbf2c8ea8829b5c476b1b9,PMC,"Serological patterns of Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae, Pasteurella multocida and Streptococcus suis in pig herds affected by pleuritis",http://dx.doi.org/10.1186/s13028-016-0252-1,PMC5050615,27716292,CC BY,"BACKGROUND: Respiratory illness is traditionally regarded as the disease of the growing pig, and has historically mainly been associated to bacterial infections with focus on Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae. These bacteria still are of great importance, but continuously increasing herd sizes have complicated the scenario and the influence of secondary invaders may have been increased. The aim of this study was to evaluate the presence of A. pleuropneumoniae and M. hyopneumoniae, as well as that of the secondary invaders Pasteurella multocida and Streptococcus suis by serology in four pig herds (A–D) using age segregated rearing systems with high incidences of pleuritic lesions at slaughter. RESULTS: Pleuritic lesions registered at slaughter ranged from 20.5 to 33.1 % in the four herds. In herd A, the levels of serum antibodies to A. pleuropneumoniae exceeded A(450) > 1.5, but not to any other microbe searched for. The seroconversion took place early during the fattening period. Similar levels of serum antibodies to A. pleuropneumoniae were also recorded in herd B, with a subsequent increase in levels of antibodies to P. multocida. Pigs seroconverted to both agents during the early phase of the fattening period. In herd C, pigs seroconverted to P. multocida during the early phase of the fattening period and thereafter to A. pleuropneumoniae. In herd D, the levels of antibodies to P. multocida exceeded A(450) > 1.0 in absence (A(450) < 0.5) of antibodies to A. pleuropneumoniae. The levels of serum antibodies to M. hyopneumoniae and to S. suis remained below A(450) < 1.0 in all four herds. Pigs seroconverted to M. hyopneumoniae late during the rearing period (herd B–D), or not at all (herd A). CONCLUSION: Different serological patterns were found in the four herds with high levels of serum antibodies to A. pleuropneumoniae and P. multocida, either alone or in combination with each other. Seroconversion to M. hyopneumoniae late during the rearing period or not at all, confirmed the positive effect of age segregated rearing in preventing or delaying infections with M. hyopneumoniae. The results obtained highlight the necessity of diagnostic investigations to define the true disease pattern in herds with a high incidence of pleuritic lesions.",2016 Oct 4,"['Wallgren, Per', 'Nörregård, Erik', 'Molander, Benedicta', 'Persson, Maria', 'Ehlorsson, Carl-Johan']",Acta Vet Scand,,,True
953d78fb78ffe2bd8db79fac2390d45bd28a4952,PMC,CCR5 ameliorates Japanese encephalitis via dictating the equilibrium of regulatory CD4(+)Foxp3(+) T and IL-17(+)CD4(+) Th17 cells,http://dx.doi.org/10.1186/s12974-016-0656-x,PMC5050958,27439902,CC BY,"BACKGROUND: CCR5 is a CC chemokine receptor involved in the migration of effector leukocytes including macrophages, NK, and T cells into inflamed tissues. Also, the role of CCR5 in CD4(+)Foxp3(+) regulatory T cell (Treg) homing has recently begun to grab attention. Japanese encephalitis (JE) is defined as severe neuroinflammation of the central nervous system (CNS) following infection with mosquito-borne flavivirus JE virus. However, the potential contribution of CCR5 to JE progression via mediating CD4(+)Foxp3(+) Treg homing has not been investigated. METHODS: Infected wild-type (Ccr5(+/+)) and CCR5-deficient (Ccr5(−/−)) mice were examined daily for mortality and clinical signs, and neuroinflammation in the CNS was evaluated by infiltration of inflammatory leukocytes and cytokine expression. In addition, viral burden, NK- and JEV-specific T cell responses were analyzed. Adoptive transfer of CCR5(+)CD4(+)Foxp3(+) Tregs was used to evaluate the role of Tregs in JE progression. RESULTS: CCR5 ablation exacerbated JE without altering viral burden in the extraneural and CNS tissues, as manifested by increased CNS infiltration of Ly-6C(hi) monocytes and Ly-6G(hi) granulocytes. Compared to Ccr5(+/+) mice, Ccr5(−/−) mice unexpectedly showed increased responses of IFN-γ(+)NK and CD8(+) T cells in the spleen, but not CD4(+) T cells. More interestingly, CCR5-ablation resulted in a skewed response to IL-17(+)CD4(+) Th17 cells and correspondingly reduced CD4(+)Foxp3(+) Tregs in the spleen and brain, which was closely associated with exacerbated JE. Our results also revealed that adoptive transfer of sorted CCR5(+)CD4(+)Foxp3(+) Tregs into Ccr5(−/−) mice could ameliorate JE progression without apparently altering the viral burden and CNS infiltration of IL-17(+)CD4(+) Th17 cells, myeloid-derived Ly-6C(hi) monocytes and Ly-6G(hi) granulocytes. Instead, adoptive transfer of CCR5(+)CD4(+)Foxp3(+) Tregs into Ccr5(−/−) mice resulted in increased expression of anti-inflammatory cytokines (IL-10 and TGF-β) in the spleen and brain, and transferred CCR5(+) Tregs were found to produce IL-10. CONCLUSIONS: CCR5 regulates JE progression via governing timely and appropriate CNS infiltration of CD4(+)Foxp3(+) Tregs, thereby facilitating host survival. Therefore, this critical and extended role of CCR5 in JE raises possible safety concerns regarding the use of CCR5 antagonists in human immunodeficiency virus (HIV)-infected individuals who inhabit regions in which both HIV and flaviviruses, such as JEV and West Nile virus, are endemic.",2016 Jul 20,"['Kim, Jin Hyoung', 'Patil, Ajit Mahadev', 'Choi, Jin Young', 'Kim, Seong Bum', 'Uyangaa, Erdenebelig', 'Hossain, Ferdaus Mohd Altaf', 'Park, Sang-Youel', 'Lee, John Hwa', 'Eo, Seong Kug']",J Neuroinflammation,,,True
691856452de91727b7b9b7644f82b4bc5876f32f,PMC,MERS-CoV at the Animal–Human Interface: Inputs on Exposure Pathways from an Expert-Opinion Elicitation,http://dx.doi.org/10.3389/fvets.2016.00088,PMC5051548,27761437,CC BY,"Nearly 4 years after the first report of the emergence of Middle-East respiratory syndrome Coronavirus (MERS-CoV) and nearly 1800 human cases later, the ecology of MERS-CoV, its epidemiology, and more than risk factors of MERS-CoV transmission between camels are poorly understood. Knowledge about the pathways and mechanisms of transmission from animals to humans is limited; as of yet, transmission risks have not been quantified. Moreover the divergent sanitary situations and exposures to animals among populations in the Arabian Peninsula, where human primary cases appear to dominate, vs. other regions in the Middle East and Africa, with no reported human clinical cases and where the virus has been detected only in dromedaries, represents huge scientific and health challenges. Here, we have used expert-opinion elicitation in order to obtain ideas on relative importance of MERS-CoV risk factors and estimates of transmission risks from various types of contact between humans and dromedaries. Fourteen experts with diverse and extensive experience in MERS-CoV relevant fields were enrolled and completed an online questionnaire that examined pathways based on several scenarios, e.g., camels–camels, camels–human, bats/other species to camels/humans, and the role of diverse biological substances (milk, urine, etc.) and potential fomites. Experts believed that dromedary camels play the largest role in MERS-CoV infection of other dromedaries; however, they also indicated a significant influence of the season (i.e. calving or weaning periods) on transmission risk. All experts thought that MERS-CoV-infected dromedaries and asymptomatic humans play the most important role in infection of humans, with bats and other species presenting a possible, but yet undefined, risk. Direct and indirect contact of humans with dromedary camels were identified as the most risky types of contact, when compared to consumption of various camel products, with estimated “most likely” incidence risks of at least 22 and 13% for direct and indirect contact, respectively. The results of our study are consistent with available, yet very limited, published data regarding the potential pathways of transmission of MERS-CoV at the animal–human interface. These results identify key knowledge gaps and highlight the need for more comprehensive, yet focused research to be conducted to better understand transmission between dromedaries and humans.",2016 Oct 5,"['Funk, Anna L.', 'Goutard, Flavie Luce', 'Miguel, Eve', 'Bourgarel, Mathieu', 'Chevalier, Veronique', 'Faye, Bernard', 'Peiris, J. S. Malik', 'Van Kerkhove, Maria D.', 'Roger, Francois Louis']",Front Vet Sci,,,True
6318351120824de3f612d0dbdd9611f4c94bf071,PMC,Saliva between normal and pathological.  Important factors in determining systemic and oral health,,PMC5052503,20112475,CC BY,"There is a tendency in current medical research to explore the importance and symptomatology of saliva. The question to which increasingly more researchers from the medico-legal, systemic and dental fields tried to answer and bring together arguments for a greater emphasis is referring to the role of saliva in the health of the patient. Up until our time, people have looked at the importance of saliva from another perspective: saliva helped in pasting envelopes or stamps, or mostly in reported cases of public speakers faced with the impossibility of having a coherent speech due to sensations of dry mouth. This ‘dry mouth’ condition, named xerostomia in medical terms, has been used since antiquity as a test in detecting lies, knowing since then that the inhibition of emotional salivary glands, the feeling of ‘dry mouth’ is caused by anxiety, thus being a potential incrimination. Although hundreds of publications have insisted on the etiology and complications of the salivary gland hypofunction, only a few health professionals used to harvest saliva tests. As in the case of urine and blood, saliva quality and quantity are affected by a multitude of medical conditions and treatments, as well as the patient's psychological state. A review of the formation, function and dysfunction of salivary glands may convey the significant role played by saliva in health and disease, especially in detection and recognition of salivary gland hypofunction, systemic disease, and the psychological states, and thus prevent complications caused by these conditions.",2009 Jul-Sep,"Iorgulescu, Gabriela",J Med Life,,,False
131e6a035170ed5bd2dba6bec02649e9508a0c55,PMC,PTEN ameliorates autoimmune arthritis through down-regulating STAT3 activation with reciprocal balance of Th17 and Tregs,http://dx.doi.org/10.1038/srep34617,PMC5052580,27708408,CC BY,"PTEN is a tyrosine phosphatase with significant function in inhibiting STAT3 activation. Recently, inactivation of STAT3 has been demonstrated as a therapeutic candidate for autoimmune arthritis. The expression of PTEN controlled by p53 regulates autoimmune arthritis through modulating the balance between Th17 and Treg. We hypothesized that PTEN regulated by p53 might reduce CIA severity and inflammatory response via inhibiting STAT3 activation. Our results revealed that PTEN could ameliorate experimental autoimmune arthritis by reducing STAT3 activity and Th17 differentiation. Systemic infusion of PTEN overexpression downregulated CIA severity. In addition, PTEN overexpression decreased the activation of T cells and modulated reciprocal differentiation of Th17 and Treg cells. We observed that PTEN expression downregulated by p53 deficiency induced the activation of STAT3. Loss of p53 exacerbated autoimmune arthritis and dysregulated the population of Th17 and Treg. These data suggest that induction of STAT3-modulatory activity of PTEN may be a therapeutic target for rheumatoid arthritis therapy.",2016 Oct 6,"['Lee, Seung Hoon', 'Park, Jin-Sil', 'Byun, Jae-Kyung', 'Jhun, JooYeon', 'Jung, KyungAh', 'Seo, Hyeon-Beom', 'Moon, Young-Mee', 'Kim, Ho-Youn', 'Park, Sung-Hwan', 'Cho, Mi-La']",Sci Rep,,,True
682ccd02287c5c36f05186e68f2cd195fcc20641,PMC,PTEN ameliorates autoimmune arthritis through down-regulating STAT3 activation with reciprocal balance of Th17 and Tregs,http://dx.doi.org/10.1038/srep34617,PMC5052580,27708408,CC BY,"PTEN is a tyrosine phosphatase with significant function in inhibiting STAT3 activation. Recently, inactivation of STAT3 has been demonstrated as a therapeutic candidate for autoimmune arthritis. The expression of PTEN controlled by p53 regulates autoimmune arthritis through modulating the balance between Th17 and Treg. We hypothesized that PTEN regulated by p53 might reduce CIA severity and inflammatory response via inhibiting STAT3 activation. Our results revealed that PTEN could ameliorate experimental autoimmune arthritis by reducing STAT3 activity and Th17 differentiation. Systemic infusion of PTEN overexpression downregulated CIA severity. In addition, PTEN overexpression decreased the activation of T cells and modulated reciprocal differentiation of Th17 and Treg cells. We observed that PTEN expression downregulated by p53 deficiency induced the activation of STAT3. Loss of p53 exacerbated autoimmune arthritis and dysregulated the population of Th17 and Treg. These data suggest that induction of STAT3-modulatory activity of PTEN may be a therapeutic target for rheumatoid arthritis therapy.",2016 Oct 6,"['Lee, Seung Hoon', 'Park, Jin-Sil', 'Byun, Jae-Kyung', 'Jhun, JooYeon', 'Jung, KyungAh', 'Seo, Hyeon-Beom', 'Moon, Young-Mee', 'Kim, Ho-Youn', 'Park, Sung-Hwan', 'Cho, Mi-La']",Sci Rep,,,False
9c1c6037784f97a987e79a92077dad0d252b7236,PMC,Irreversible inhibitors of the 3C protease of Coxsackie virus through templated assembly of protein-binding fragments,http://dx.doi.org/10.1038/ncomms12761,PMC5052702,27677239,CC BY,"Small-molecule fragments binding to biomacromolecules can be starting points for the development of drugs, but are often difficult to detect due to low affinities. Here we present a strategy that identifies protein-binding fragments through their potential to induce the target-guided formation of covalently bound, irreversible enzyme inhibitors. A protein-binding nucleophile reacts reversibly with a bis-electrophilic warhead, thereby positioning the second electrophile in close proximity of the active site of a viral protease, resulting in the covalent de-activation of the enzyme. The concept is implemented for Coxsackie virus B3 3C protease, a pharmacological target against enteroviral infections. Using an aldehyde-epoxide as bis-electrophile, active fragment combinations are validated through measuring the protein inactivation rate and by detecting covalent protein modification in mass spectrometry. The structure of one enzyme–inhibitor complex is determined by X-ray crystallography. The presented warhead activation assay provides potent non-peptidic, broad-spectrum inhibitors of enteroviral proteases.",2016 Sep 28,"['Becker, Daniel', 'Kaczmarska, Zuzanna', 'Arkona, Christoph', 'Schulz, Robert', 'Tauber, Carolin', 'Wolber, Gerhard', 'Hilgenfeld, Rolf', 'Coll, Miquel', 'Rademann, Jörg']",Nat Commun,,,True
4146f749b0883891603380e62be449df9a94a1a3,PMC,Irreversible inhibitors of the 3C protease of Coxsackie virus through templated assembly of protein-binding fragments,http://dx.doi.org/10.1038/ncomms12761,PMC5052702,27677239,CC BY,"Small-molecule fragments binding to biomacromolecules can be starting points for the development of drugs, but are often difficult to detect due to low affinities. Here we present a strategy that identifies protein-binding fragments through their potential to induce the target-guided formation of covalently bound, irreversible enzyme inhibitors. A protein-binding nucleophile reacts reversibly with a bis-electrophilic warhead, thereby positioning the second electrophile in close proximity of the active site of a viral protease, resulting in the covalent de-activation of the enzyme. The concept is implemented for Coxsackie virus B3 3C protease, a pharmacological target against enteroviral infections. Using an aldehyde-epoxide as bis-electrophile, active fragment combinations are validated through measuring the protein inactivation rate and by detecting covalent protein modification in mass spectrometry. The structure of one enzyme–inhibitor complex is determined by X-ray crystallography. The presented warhead activation assay provides potent non-peptidic, broad-spectrum inhibitors of enteroviral proteases.",2016 Sep 28,"['Becker, Daniel', 'Kaczmarska, Zuzanna', 'Arkona, Christoph', 'Schulz, Robert', 'Tauber, Carolin', 'Wolber, Gerhard', 'Hilgenfeld, Rolf', 'Coll, Miquel', 'Rademann, Jörg']",Nat Commun,,,True
5c56a1f3c469648d2e726e5c0d7bca623749a10b,PMC,Irreversible inhibitors of the 3C protease of Coxsackie virus through templated assembly of protein-binding fragments,http://dx.doi.org/10.1038/ncomms12761,PMC5052702,27677239,CC BY,"Small-molecule fragments binding to biomacromolecules can be starting points for the development of drugs, but are often difficult to detect due to low affinities. Here we present a strategy that identifies protein-binding fragments through their potential to induce the target-guided formation of covalently bound, irreversible enzyme inhibitors. A protein-binding nucleophile reacts reversibly with a bis-electrophilic warhead, thereby positioning the second electrophile in close proximity of the active site of a viral protease, resulting in the covalent de-activation of the enzyme. The concept is implemented for Coxsackie virus B3 3C protease, a pharmacological target against enteroviral infections. Using an aldehyde-epoxide as bis-electrophile, active fragment combinations are validated through measuring the protein inactivation rate and by detecting covalent protein modification in mass spectrometry. The structure of one enzyme–inhibitor complex is determined by X-ray crystallography. The presented warhead activation assay provides potent non-peptidic, broad-spectrum inhibitors of enteroviral proteases.",2016 Sep 28,"['Becker, Daniel', 'Kaczmarska, Zuzanna', 'Arkona, Christoph', 'Schulz, Robert', 'Tauber, Carolin', 'Wolber, Gerhard', 'Hilgenfeld, Rolf', 'Coll, Miquel', 'Rademann, Jörg']",Nat Commun,,,False
d09b4a75ec07b2369281492d99c716bc3e0eba5e,PMC,Preparedness for Zika virus testing in the World Health Organization Western Pacific Region,http://dx.doi.org/10.5365/WPSAR.2016.7.1.007,PMC5052899,27757256,CC BY,"On 1 February 2016, the World Health Organization (WHO) declared that clusters of microcephaly cases and other neurological disorders occurring in Zika virus (ZIKV)-affected areas constituted a public health emergency of international concern. Increased surveillance of the virus, including the requirement for laboratory confirmation of infection, was recommended. The WHO Regional Office for the Western Pacific therefore initiated a rapid survey among national-level public health laboratories in 19 countries and areas to determine regional capacity for ZIKV detection. The survey indicated that 16/19 (84%) countries had capacity for molecular detection of ZIKV while others facilitated testing through referral. These results suggest that robust laboratory capacity is in place to support ZIKV surveillance in the Western Pacific Region.",2016 Mar 31,"['Squires, Raynal C', 'Konings, Frank', None]",Western Pac Surveill Response J,,,True
bedec26c3620f77256b9abfba6f57bc7570297b5,PMC,Perceptions on the risk communication strategy during the 2013 avian influenza A/H7N9 outbreak in humans in China: a focus group study,http://dx.doi.org/10.5365/WPSAR.2016.7.1.005,PMC5053133,27757257,CC BY,"OBJECTIVE: To identify the general public’s perceptions of the overall risk communication strategy carried out by Chinese public health agencies during the first wave of avian influenza A(H7N9) outbreak in humans in 2013. METHODS: Participants were recruited from communities in Beijing, Lanzhou and Hangzhou, China in May and June 2013 by convenience sampling. Demographics and other relevant information were collected using a self-administered questionnaire. Focus group interviews were conducted using a set of nine pre-developed questions and a tested moderator guide. The interviews were audio recorded and were transcribed verbatim. The constant comparative method was used to identify trends and themes. RESULTS: A total of nine focus group interviews, with 94 participants recruited from nine communities, were conducted. Most participants received H7N9 information via television and the Internet. Most the participants appreciated the transparency and timeliness of the information released by the government. They expressed a sense of trust in the recommended public health advice and followed most of them. The participants suggested that the government release more information about clinical treatment outcomes, have more specific health recommendations that are practical to their settings and expand the use of new media channels for risk communication. CONCLUSION: The public perceived the overall risk communication strategy by the Chinese public health agencies as effective, though the moderator had a governmental agency title that might have biased the results. There is a need to expand the use of social media for risk communication in the future.",2016 Jul 11,"['Li, Richun', 'Xie, Ruiqian', 'Yang, Chong', 'Frost, Melinda']",Western Pac Surveill Response J,,,True
acf54b736dacc46a77d7f071f9c0cb9c14b2fc19,PMC,Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence,http://dx.doi.org/10.1371/journal.pntd.0005047,PMC5053439,27711108,CC BY,"Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear. To examine this, we generated two RVFV MP-12 strain-derived mutant viruses. Each carried mutations in NSs that specifically targeted its general transcription inhibition function without affecting its ability to degrade PKR and inhibit IFN-β promoter induction, through its interaction with Sin3-associated protein 30, a part of the repressor complex at the IFN-β promoter. Using these mutant viruses, we have dissected the transcription inhibition function of NSs and examined its importance in RVFV virulence. Both NSs mutant viruses exhibited a differentially impaired ability to inhibit host transcription when compared with MP-12. It has been reported that NSs suppresses general transcription by interfering with the formation of the transcription factor IIH complex, through the degradation of the p62 subunit and sequestration of the p44 subunit. Our study results lead us to suggest that the ability of NSs to induce p62 degradation is the major contributor to its general transcription inhibition property, whereas its interaction with p44 may not play a significant role in this function. Importantly, RVFV MP-12-NSs mutant viruses with an impaired general transcription inhibition function showed a reduced cytotoxicity in cell culture and attenuated virulence in young mice, compared with its parental virus MP-12, highlighting the contribution of NSs-mediated general transcription inhibition towards RVFV virulence.",2016 Oct 6,"['Terasaki, Kaori', 'Ramirez, Sydney I.', 'Makino, Shinji']",PLoS Negl Trop Dis,,,True
0ee1c7181e45a196ce3e91a128cc64426fa6de5e,PMC,XRN1 Is a Species-Specific Virus Restriction Factor in Yeasts,http://dx.doi.org/10.1371/journal.ppat.1005890,PMC5053509,27711183,CC BY,"In eukaryotes, the degradation of cellular mRNAs is accomplished by Xrn1 and the cytoplasmic exosome. Because viral RNAs often lack canonical caps or poly-A tails, they can also be vulnerable to degradation by these host exonucleases. Yeast lack sophisticated mechanisms of innate and adaptive immunity, but do use RNA degradation as an antiviral defense mechanism. We find a highly refined, species-specific relationship between Xrn1p and the “L-A” totiviruses of different Saccharomyces yeast species. We show that the gene XRN1 has evolved rapidly under positive natural selection in Saccharomyces yeast, resulting in high levels of Xrn1p protein sequence divergence from one yeast species to the next. We also show that these sequence differences translate to differential interactions with the L-A virus, where Xrn1p from S. cerevisiae is most efficient at controlling the L-A virus that chronically infects S. cerevisiae, and Xrn1p from S. kudriavzevii is most efficient at controlling the L-A-like virus that we have discovered within S. kudriavzevii. All Xrn1p orthologs are equivalent in their interaction with another virus-like parasite, the Ty1 retrotransposon. Thus, Xrn1p appears to co-evolve with totiviruses to maintain its potent antiviral activity and limit viral propagation in Saccharomyces yeasts. We demonstrate that Xrn1p physically interacts with the Gag protein encoded by the L-A virus, suggesting a host-virus interaction that is more complicated than just Xrn1p-mediated nucleolytic digestion of viral RNAs.",2016 Oct 6,"['Rowley, Paul A.', 'Ho, Brandon', 'Bushong, Sarah', 'Johnson, Arlen', 'Sawyer, Sara L.']",PLoS Pathog,,,True
4562513d3f2f9c259d9ce5a0eae9233dbf8b8f87,PMC,Mitophagy in TGEV infection counteracts oxidative stress and apoptosis,http://dx.doi.org/10.18632/oncotarget.8345,PMC5053637,27027356,CC BY,"The intestinal epithelial cells contain a large number of mitochondria for persisting absorption and barrier function. Selective autophagy of mitochondria (mitophagy) plays an important role in the quality control of mitochondria and maintenance of cell homeostasis. Transmissible gastroenteritis virus (TGEV) is a porcine enteropathogenic coronavirus which induces malabsorption and lethal watery diarrhea in suckling piglets. The role of mitophagy in the pathological changes caused by TGEV infection is unclear. Here, we report that TGEV induces mitophagy to suppress oxidative stress and apoptosis induced by viral infection in porcine epithelial cells (IPEC-J2). We observe that TGEV infection induce mitochondrial injury, abnormal morphology, complete mitophagy, and without obvious apoptosis after TGEV infection. Meanwhile, TGEV also induces DJ-1 and some antioxidant genes upregulation to suppress oxidative stress induced by viral infection. Furthermore, silencing DJ-1 inhibit mitophagy and increase apoptosis after TGEV infection. In addition, we demonstrate for the first time that viral nucleocapsid protein (N) is located in mitochondria and mitophagosome during virus infection or be expressed alone. Those results provide a novel perspective for further improvement of prevention and treatment in TGEV infection. These results suggest that TGEV infection induce mitophagy to promote cell survival and possibly viral infection.",2016 Mar 24,"['Zhu, Liqi', 'Mou, Chunxiao', 'Yang, Xing', 'Lin, Jian', 'Yang, Qian']",Oncotarget,,,True
bd81a285e936f3dd23d16b859c50e05716066c66,PMC,Mitophagy in TGEV infection counteracts oxidative stress and apoptosis,http://dx.doi.org/10.18632/oncotarget.8345,PMC5053637,27027356,CC BY,"The intestinal epithelial cells contain a large number of mitochondria for persisting absorption and barrier function. Selective autophagy of mitochondria (mitophagy) plays an important role in the quality control of mitochondria and maintenance of cell homeostasis. Transmissible gastroenteritis virus (TGEV) is a porcine enteropathogenic coronavirus which induces malabsorption and lethal watery diarrhea in suckling piglets. The role of mitophagy in the pathological changes caused by TGEV infection is unclear. Here, we report that TGEV induces mitophagy to suppress oxidative stress and apoptosis induced by viral infection in porcine epithelial cells (IPEC-J2). We observe that TGEV infection induce mitochondrial injury, abnormal morphology, complete mitophagy, and without obvious apoptosis after TGEV infection. Meanwhile, TGEV also induces DJ-1 and some antioxidant genes upregulation to suppress oxidative stress induced by viral infection. Furthermore, silencing DJ-1 inhibit mitophagy and increase apoptosis after TGEV infection. In addition, we demonstrate for the first time that viral nucleocapsid protein (N) is located in mitochondria and mitophagosome during virus infection or be expressed alone. Those results provide a novel perspective for further improvement of prevention and treatment in TGEV infection. These results suggest that TGEV infection induce mitophagy to promote cell survival and possibly viral infection.",2016 Mar 24,"['Zhu, Liqi', 'Mou, Chunxiao', 'Yang, Xing', 'Lin, Jian', 'Yang, Qian']",Oncotarget,,,False
206121388211d800150c316cd04daeaec547032b,PMC,Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells,http://dx.doi.org/10.1038/srep34589,PMC5054393,27713552,CC BY,"The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.",2016 Oct 7,"['Hölzer, Martin', 'Krähling, Verena', 'Amman, Fabian', 'Barth, Emanuel', 'Bernhart, Stephan H.', 'Carmelo, Victor A. O.', 'Collatz, Maximilian', 'Doose, Gero', 'Eggenhofer, Florian', 'Ewald, Jan', 'Fallmann, Jörg', 'Feldhahn, Lasse M.', 'Fricke, Markus', 'Gebauer, Juliane', 'Gruber, Andreas J.', 'Hufsky, Franziska', 'Indrischek, Henrike', 'Kanton, Sabina', 'Linde, Jörg', 'Mostajo, Nelly', 'Ochsenreiter, Roman', 'Riege, Konstantin', 'Rivarola-Duarte, Lorena', 'Sahyoun, Abdullah H.', 'Saunders, Sita J.', 'Seemann, Stefan E.', 'Tanzer, Andrea', 'Vogel, Bertram', 'Wehner, Stefanie', 'Wolfinger, Michael T.', 'Backofen, Rolf', 'Gorodkin, Jan', 'Grosse, Ivo', 'Hofacker, Ivo', 'Hoffmann, Steve', 'Kaleta, Christoph', 'Stadler, Peter F.', 'Becker, Stephan', 'Marz, Manja']",Sci Rep,,,True
d64f2458851579ca8041d557f759eb0f8d515d6c,PMC,Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells,http://dx.doi.org/10.1038/srep34589,PMC5054393,27713552,CC BY,"The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.",2016 Oct 7,"['Hölzer, Martin', 'Krähling, Verena', 'Amman, Fabian', 'Barth, Emanuel', 'Bernhart, Stephan H.', 'Carmelo, Victor A. O.', 'Collatz, Maximilian', 'Doose, Gero', 'Eggenhofer, Florian', 'Ewald, Jan', 'Fallmann, Jörg', 'Feldhahn, Lasse M.', 'Fricke, Markus', 'Gebauer, Juliane', 'Gruber, Andreas J.', 'Hufsky, Franziska', 'Indrischek, Henrike', 'Kanton, Sabina', 'Linde, Jörg', 'Mostajo, Nelly', 'Ochsenreiter, Roman', 'Riege, Konstantin', 'Rivarola-Duarte, Lorena', 'Sahyoun, Abdullah H.', 'Saunders, Sita J.', 'Seemann, Stefan E.', 'Tanzer, Andrea', 'Vogel, Bertram', 'Wehner, Stefanie', 'Wolfinger, Michael T.', 'Backofen, Rolf', 'Gorodkin, Jan', 'Grosse, Ivo', 'Hofacker, Ivo', 'Hoffmann, Steve', 'Kaleta, Christoph', 'Stadler, Peter F.', 'Becker, Stephan', 'Marz, Manja']",Sci Rep,,,True
6ad4ebbfb6b68ed621ad2d67db85fac7ab6dc3cc,PMC,Fundamentals of aerosol therapy in critical care,http://dx.doi.org/10.1186/s13054-016-1448-5,PMC5054555,27716346,CC BY,"Drug dosing in critically ill patients is challenging due to the altered drug pharmacokinetics–pharmacodynamics associated with systemic therapies. For many drug therapies, there is potential to use the respiratory system as an alternative route for drug delivery. Aerosol drug delivery can provide many advantages over conventional therapy. Given that respiratory diseases are the commonest causes of critical illness, use of aerosol therapy to provide high local drug concentrations with minimal systemic side effects makes this route an attractive option. To date, limited evidence has restricted its wider application. The efficacy of aerosol drug therapy depends on drug-related factors (particle size, molecular weight), device factors, patient-related factors (airway anatomy, inhalation patterns) and mechanical ventilation-related factors (humidification, airway). This review identifies the relevant factors which require attention for optimization of aerosol drug delivery that can achieve better drug concentrations at the target sites and potentially improve clinical outcomes.",2016 Oct 7,"['Dhanani, Jayesh', 'Fraser, John F.', 'Chan, Hak-Kim', 'Rello, Jordi', 'Cohen, Jeremy', 'Roberts, Jason A.']",Crit Care,,,True
adbfd5297c83ec9c3bec89f2cf68b2715034c4d4,PMC,Therapeutic potential of the renin angiotensin system in ischaemic stroke,http://dx.doi.org/10.1186/s13231-016-0022-1,PMC5054604,27761230,CC BY,"The renin angiotensin system (RAS) consists of the systemic hormone system, critically involved in regulation and homeostasis of normal physiological functions [i.e. blood pressure (BP), blood volume regulation], and an independent brain RAS, which is involved in the regulation of many functions such as memory, central control of BP and metabolic functions. In general terms, the RAS consists of two opposing axes; the ‘classical axis’ mediated primarily by Angiotensin II (Ang II), and the ‘alternative axis’ mediated mainly by Angiotensin-(1–7) (Ang-(1–7)). An imbalance of these two opposing axes is thought to exist between genders and is thought to contribute to the pathology of cardiovascular conditions such as hypertension, a stroke co-morbidity. Ischaemic stroke pathophysiology has been shown to be influenced by components of the RAS with specific RAS receptor antagonists and agonists improving outcome in experimental models of stroke. Manipulation of the two opposing axes following acute ischaemic stroke may provide an opportunity for protection of the neurovascular unit, particularly in the presence of pre-existing co-morbidities where the balance may be shifted. In the present review we will give an overview of the experimental stroke studies that have investigated pharmacological interventions of the RAS.",2016 Oct 7,"['Arroja, Mariana Moreira Coutinho', 'Reid, Emma', 'McCabe, Christopher']",Exp Transl Stroke Med,,,True
af6dacec0a1ba933a47d7451ef69ea06f7029882,PMC,Ability of device to collect bacteria from cough aerosols generated by adults with cystic fibrosis,http://dx.doi.org/10.12688/f1000research.9251.1,PMC5054809,27781088,CC BY,"Background: Identifying lung pathogens and acute spikes in lung counts remain a challenge in the treatment of patients with cystic fibrosis (CF). Bacteria from the deep lung may be sampled from aerosols produced during coughing. Methods: A new device was used to collect and measure bacteria levels from cough aerosols of patients with CF. Sputum and oral specimens were also collected and measured for comparison. Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus mitis were detected in specimens using Real-Time Polymerase Chain Reaction (RT-PCR) molecular assays. Results: Twenty adult patients with CF and 10 healthy controls participated. CF related bacteria (CFRB) were detected in 13/20 (65%) cough specimens versus 15/15 (100%) sputum specimens. Commensal S. mitis was present in 0/17 (0%, p=0.0002) cough specimens and 13/14 (93%) sputum samples. In normal controls, no bacteria were collected in cough specimens but 4/10 (40%) oral specimens were positive for CFRB. Conclusions: Non-invasive cough aerosol collection may detect lower respiratory pathogens in CF patients, with similar specificity and sensitivity to rates detected by BAL, without contamination by oral CFRB or commensal bacteria.",2016 Aug 5,"['Ku, David N.', 'Ku, Sarah K.', 'Helfman, Beth', 'McCarty, Nael A.', 'Wolff, Bernard J.', 'Winchell, Jonas M.', 'Anderson, Larry J.']",F1000Res,,,True
4f695bec496fb166d09c3377627d86cc587c2f27,PMC,Cathepsin L Helps to Defend Mice from Infection with Influenza A,http://dx.doi.org/10.1371/journal.pone.0164501,PMC5055332,27716790,CC0,"Host-derived proteases can augment or help to clear infections. This dichotomy is exemplified by cathepsin L (CTSL), which helps Hendra virus and SARS coronavirus to invade cells, but is essential for survival in mice with mycoplasma pneumonia. The present study tested the hypothesis that CTSL protects mice from serious consequences of infection by the orthomyxovirus influenza A, which is thought to be activated by host-supplied proteases other than CTSL. Ctsl(-/-) mice infected with influenza A/Puerto Rico/8/34(H1N1) had larger lung viral loads and higher mortality than infected Ctsl(+/+) mice. Lung inflammation in surviving infected mice peaked 14 days after initial infection, accompanied marked focal distal airway bronchiolization and epithelial metaplasia followed by desquamation and fibrotic interstitial remodeling, and persisted for at least 6 weeks. Most deaths occurred during the second week of infection in both groups of mice. In contrast to mycoplasma pneumonia, infiltrating cells were predominantly mononuclear rather than polymorphonuclear. The histopathology of lung inflammation and remodeling in survivors was similar in Ctsl(-/-) and Ctsl(+/+) mice, although Ctsl(+/+) mice cleared immunoreactive virus sooner. Furthermore, Ctsl(-/-) mice had profound deficits in CD4+ lymphocytes before and after infection and weaker production of pathogen-specific IgG. Thus, CTSL appears to support innate as well as adaptive responses, which confer a survival advantage on mice infected with the orthomyxovirus influenza A.",2016 Oct 7,"['Xu, Xiang', 'Greenland, John R.', 'Gotts, Jeffrey E.', 'Matthay, Michael A.', 'Caughey, George H.']",PLoS One,,,True
d8eb14ca18661130fdaf099482d6cd5b46032efe,PMC,"Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9), a biomarker for various pathological conditions, is produced in post-blood collection by fibrinolysis and coagulation factors",http://dx.doi.org/10.1186/s12014-016-9129-6,PMC5055723,27761105,CC BY,"BACKGROUND: Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9) is a new serum biomarker for chronic hepatitis that was discovered by proteomics analysis. Previous studies have shown that FIC5.9 is derived from the C-terminal region of fibrinogen alpha chain and the serum levels of FIC5.9 decrease in chronic hepatitis. It also have been reported that FIC5.9 cannot be detected in the blood stream of the systemic circulation and it is released from fibrinogen during blood clotting in collecting tube. However, the mechanism of FIC5.9 releasing from fibrinogen is unclear. METHODS: We formulated a hypothesis that FIC5.9 is released by enzymes that are activated by post-blood collection and may be coagulation and fibrinolysis factors. In this study, we analyzed the mechanisms of FIC5.9 releasing from fibrinogen in healthy blood. RESULTS: Our analysis showed that thrombin acts as an initiator for FIC5.9 releasing, and that mainly plasmin cleaves N-terminal end of FIC5.9 and neutrophil elastase cleave C-terminal end of FIC5.9. CONCLUSION: FIC5.9 reflects minute changes in coagulation and fibrinolysis factors and may be associated with pathological conditions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12014-016-9129-6) contains supplementary material, which is available to authorized users.",2016 Oct 7,"['Kikuchi, Wataru', 'Nishimura, Motoi', 'Kuga, Takahisa', 'Tsuchida, Sachio', 'Saito, Tatsuya', 'Satoh, Mamoru', 'Noda, Kenta', 'Kodera, Yoshio', 'Tomonaga, Takeshi', 'Nomura, Fumio']",Clin Proteomics,,,True
58a21f91c8d3c79e8be084088092f29dec2fc4d3,PMC,Genetic dissection of host immune response in pneumonia development and progression,http://dx.doi.org/10.1038/srep35021,PMC5057148,27725770,CC BY,"The role of host genetic variation in pneumonia development and outcome is poorly understood. We studied common polymorphisms in the genes of proinflammatory cytokines (IL6 rs1800795, IL8 rs4073, IL1B rs16944), anti-inflammatory cytokines (IL10 rs1800896, IL4 rs2243250, IL13 rs20541) and toll-like receptors (TLR2 rs5743708 and rs4696480, TLR4 rs4986791, TLR9 rs352139, rs5743836 and rs187084) in patients with community-acquired pneumonia (CAP) (390 cases, 203 controls) and nosocomial pneumonia (355 cases, 216 controls). Experimental data were included in a series of 11 meta-analyses and eight subset analyses related to pneumonia susceptibility and outcome. TLR2 rs5743708 minor genotype appeared to be associated with CAP/Legionnaires’ disease/pneumococcal disease. In CAP patients, the IL6 rs1800795-C allele was associated with severe sepsis/septic shock/severe systemic inflammatory response, while the IL10 rs1800896-A allele protected against the development of these critical conditions. To contribute to deciphering of the above results, we performed an in silico analysis and a qualitative synthesis of literature data addressing basal and stimulated genotype-specific expression level. This data together with database information on transcription factors’ affinity changes caused by SNPs in putative promoter regions, the results of linkage disequilibrium analysis along with SNPs functional annotations supported assumptions about the complexity underlying the revealed associations.",2016 Oct 11,"['Smelaya, Tamara V.', 'Belopolskaya, Olesya B.', 'Smirnova, Svetlana V.', 'Kuzovlev, Artem N.', 'Moroz, Viktor V.', 'Golubev, Arkadiy M.', 'Pabalan, Noel A.', 'Salnikova, Lyubov E.']",Sci Rep,,,True
8764d0cec1713833f147b13fd476ae8fac42c600,PMC,Genetic dissection of host immune response in pneumonia development and progression,http://dx.doi.org/10.1038/srep35021,PMC5057148,27725770,CC BY,"The role of host genetic variation in pneumonia development and outcome is poorly understood. We studied common polymorphisms in the genes of proinflammatory cytokines (IL6 rs1800795, IL8 rs4073, IL1B rs16944), anti-inflammatory cytokines (IL10 rs1800896, IL4 rs2243250, IL13 rs20541) and toll-like receptors (TLR2 rs5743708 and rs4696480, TLR4 rs4986791, TLR9 rs352139, rs5743836 and rs187084) in patients with community-acquired pneumonia (CAP) (390 cases, 203 controls) and nosocomial pneumonia (355 cases, 216 controls). Experimental data were included in a series of 11 meta-analyses and eight subset analyses related to pneumonia susceptibility and outcome. TLR2 rs5743708 minor genotype appeared to be associated with CAP/Legionnaires’ disease/pneumococcal disease. In CAP patients, the IL6 rs1800795-C allele was associated with severe sepsis/septic shock/severe systemic inflammatory response, while the IL10 rs1800896-A allele protected against the development of these critical conditions. To contribute to deciphering of the above results, we performed an in silico analysis and a qualitative synthesis of literature data addressing basal and stimulated genotype-specific expression level. This data together with database information on transcription factors’ affinity changes caused by SNPs in putative promoter regions, the results of linkage disequilibrium analysis along with SNPs functional annotations supported assumptions about the complexity underlying the revealed associations.",2016 Oct 11,"['Smelaya, Tamara V.', 'Belopolskaya, Olesya B.', 'Smirnova, Svetlana V.', 'Kuzovlev, Artem N.', 'Moroz, Viktor V.', 'Golubev, Arkadiy M.', 'Pabalan, Noel A.', 'Salnikova, Lyubov E.']",Sci Rep,,,True
27f21ae7789e41a6de01554cdae09cb93ef8524f,PMC,Epidemiological and pathological study of feline morbillivirus infection in domestic cats in Japan,http://dx.doi.org/10.1186/s12917-016-0853-y,PMC5057488,27724851,CC BY,"BACKGROUND: Feline morbillivirus (FmoPV) is a novel paramyxovirus found to infect domestic cats. FmoPV has been isolated in several countries in Asia and Europe and is considered to have genetic diversity. Also, it is suspected to be associated with feline renal diseases including tubulointerstitial nephritis (TIN), which affects domestic cats with a high incidence rate. RESULTS: To clarify the state of FmoPV infection among domestic cats in Japan, an epidemiological survey was conducted. Twenty-one out of 100 cats were found to have serum antibodies (Ab) against FmoPV-N protein by indirect immunofluorescence assay (IF) using FmoPV-N protein-expressing HeLa cells. Twenty-two of the cats were positive for FmoPV RNA in the urine and/or renal tissues. In total, 29 cats were positive for Ab and/or viral RNA. These FmoPV-infected cats were classified into three different phases of infection: RNA+/Ab + (14 cats), RNA+/Ab- (8 cats) and RNA-/Ab + (7 cats). In immunohistochemistry (IHC), 19 out of 29 cats were positive for FmoPV-N protein in kidney tissues; however, the FmoPV-N protein was located in the inflammatory lesions with severe grade in only four out of the 19 cats. Since 15 out of 29 infected cats were positive for viral RNA and Ab, approximately half of the infected cats were persistently infected with FmoPV. CONCLUSIONS: A statistically significant difference was observed between infection of FmoPV and the presence of inflammatory changes in renal lesions, indicating a relationship between FmoPV infection and feline renal diseases. However, we could not obtain histopathological evidence of a relationship between FmoPV infection and TIN.",2016 Oct 11,"['Park, Eun-Sil', 'Suzuki, Michio', 'Kimura, Masanobu', 'Mizutani, Hiroshi', 'Saito, Ryuichi', 'Kubota, Nami', 'Hasuike, Youko', 'Okajima, Jungo', 'Kasai, Hidemi', 'Sato, Yuko', 'Nakajima, Noriko', 'Maruyama, Keiji', 'Imaoka, Koichi', 'Morikawa, Shigeru']",BMC Vet Res,,,True
047a76d5e047a00728847bcdd162cb925486d0ab,PMC,A Computer-Aided Detection System for Digital Chest Radiographs,http://dx.doi.org/10.1155/2016/8208923,PMC5058572,27372536,CC BY,"Computer-aided detection systems aim at the automatic detection of diseases using different medical imaging modalities. In this paper, a novel approach to detecting normality/pathology in digital chest radiographs is proposed. The problem tackled is complicated since it is not focused on particular diseases but anything that differs from what is considered as normality. First, the areas of interest of the chest are found using template matching on the images. Then, a texture descriptor called local binary patterns (LBP) is computed for those areas. After that, LBP histograms are applied in a classifier algorithm, which produces the final normality/pathology decision. Our experimental results show the feasibility of the proposal, with success rates above 87% in the best cases. Moreover, our technique is able to locate the possible areas of pathology in nonnormal radiographs. Strengths and limitations of the proposed approach are described in the Conclusions.",2016 May 31,"['Carrillo-de-Gea, Juan Manuel', 'García-Mateos, Ginés', 'Fernández-Alemán, José Luis', 'Hernández-Hernández, José Luis']",J Healthc Eng,,,True
9cfaf4c8791d75c45d2d5c52a6e2da74363d2565,PMC,"Epidemiology, Co-Infections, and Outcomes of Viral Pneumonia in Adults: An Observational Cohort Study",http://dx.doi.org/10.1097/MD.0000000000002332,PMC5058945,26683973,CC BY,"Advanced technologies using polymerase-chain reaction have allowed for increased recognition of viral respiratory infections including pneumonia. Co-infections have been described for several respiratory viruses, especially with influenza. Outcomes of viral pneumonia, including cases with co-infections, have not been well described. This was observational cohort study conducted to describe hospitalized patients with viral pneumonia including co-infections, clinical outcomes, and predictors of mortality. Patients admitted from March 2013 to November 2014 with a positive respiratory virus panel (RVP) and radiographic findings of pneumonia within 48 h of the index RVP were included. Co-respiratory infection (CRI) was defined as any organism identification from a respiratory specimen within 3 days of the index RVP. Predictors of in-hospital mortality on univariate analysis were evaluated in a multivariate model. Of 284 patients with viral pneumonia, a majority (51.8%) were immunocompromised. A total of 84 patients (29.6%) were found to have a CRI with 48 (57.6%) having a bacterial CRI. Viral CRI with HSV, CMV, or both occurred in 28 patients (33.3%). Fungal (16.7%) and other CRIs (7.1%) were less common. Many patients required mechanical ventilation (54%) and vasopressor support (36%). Overall in-hospital mortality was high (23.2%) and readmissions were common with several patients re-hospitalized within 30 (21.1%) and 90 days (36.7%) of discharge. Predictors of in-hospital mortality on multivariate regression included severity of illness factors, stem-cell transplant, and identification of multiple respiratory viruses. In conclusion, hospital mortality is high among adult patients with viral pneumonia and patients with multiple respiratory viruses identified may be at a higher risk.",2015 Dec 18,"['Crotty, Matthew P.', 'Meyers, Shelby', 'Hampton, Nicholas', 'Bledsoe, Stephanie', 'Ritchie, David J.', 'Buller, Richard S.', 'Storch, Gregory A.', 'Micek, Scott T.', 'Kollef, Marin H.']",Medicine (Baltimore),,,True
e6515195e0fdd7f1fb437a01b8737685d6d92765,PMC,"Phylogenetic analysis of human rhinoviruses collected over four successive years in Sydney, Australia",http://dx.doi.org/10.1111/irv.12404,PMC5059946,27383422,CC BY,"BACKGROUND: Human rhinoviruses (HRV) cause a wide spectrum of disease, ranging from a mild influenza‐like illness (ILI) to severe respiratory infection. Molecular epidemiological data are limited for HRV circulating in the Southern Hemisphere. OBJECTIVES: To identify the species and genotypes of HRV from clinical samples collected in Sydney, Australia, from 2006 to 2009. METHODS: Combined nose and throat swabs or nasopharyngeal aspirates collected from individuals with ILI were tested for HRV using real‐time reverse‐transcriptase polymerase chain reaction (RT‐PCR). Sequencing data of 5′UTR and VP4/VP2 coding regions on RT‐PCR‐positive specimens were analysed. RESULTS: Human rhinoviruses were detected by real‐time PCR in 20.9% (116/555) of samples tested. Phylogenetic analysis of 5′UTR and VP4/VP2 on HRV‐positive samples was concordant in the grouping of HRV A and B species but not HRV C species. Eighty per cent (16/20) of sequences that grouped as HRV C in the VP4/VP2 tree clustered as HRV A, alongside some previously described C strains as subspecies C/A. Discordant branching was seen within HRV A group: two sequences clustering as A in the VP4/VP2 tree branched within the C/A subspecies in the 5′UTR tree, and one sequence showed identity to different HRV A strains in the two genes. The prevalence of HRV C and C/A species was greater in paediatric compared to adult patients (47.9% vs 25.5%, P = .032). CONCLUSION: Human rhinoviruses are a common cause of respiratory infections, and HRV C is present in the Southern Hemisphere. Sequencing of multiple HRV regions may be necessary to determine exact phylogenetic relationships.",2016 Nov 9,"['Ratnamohan, Vigneswary M.', 'Zeng, Frank', 'Donovan, Linda', 'MacIntyre, Chandini R.', 'Kok, Jen', 'Dwyer, Dominic E.']",Influenza Other Respir Viruses,,,True
8688ca00892a6134485b2d9dd30f95e7aad1a3d8,PMC,"Expatriates’ Multiple Fears, from Terrorism to Working Conditions: Development of a Model",http://dx.doi.org/10.3389/fpsyg.2016.01571,PMC5062027,27790173,CC BY,"Companies’ internationalization appears to be fundamental in the current globalized and competitive environment and seems important not only for organizational success, but also for societal development and sustainability. On one hand, global business increases the demand for managers for international assignment. On the other hand, emergent fears, such as terrorism, seem to be developing around the world, enhancing the risk of expatriates’ potential health problems. The purpose of this paper is to examine the relationships between the emergent concept of fear of expatriation with further workplace fears (economic crisis and dangerous working conditions) and with mental health problems. The study uses a quantitative design. Self-reported data were collected from 265 Italian expatriate workers assigned to both Italian and worldwide projects. Structural equation model analyses showed that fear of expatriation mediates the relationship of mental health with fear of economic crisis and with perceived dangerous working conditions. As expected, in addition to fear, worries of expatriation are also related to further fears. Although, the study is based on self-reports and the cross-sectional study design limits the possibility of making causal inferences, the new constructs introduced add to previous research.",2016 Oct 13,"['Giorgi, Gabriele', 'Montani, Francesco', 'Fiz-Perez, Javier', 'Arcangeli, Giulio', 'Mucci, Nicola']",Front Psychol,,,True
65c8138a4905491ab3bcd6aa58320408abecc9e7,PMC,Identification of Novel Rosavirus Species That Infects Diverse Rodent Species and Causes Multisystemic Dissemination in Mouse Model,http://dx.doi.org/10.1371/journal.ppat.1005911,PMC5063349,27737017,CC BY,"While novel picornaviruses are being discovered in rodents, their host range and pathogenicity are largely unknown. We identified two novel picornaviruses, rosavirus B from the street rat, Norway rat, and rosavirus C from five different wild rat species (chestnut spiny rat, greater bandicoot rat, Indochinese forest rat, roof rat and Coxing's white-bellied rat) in China. Analysis of 13 complete genome sequences showed that “Rosavirus B” and “Rosavirus C” represent two potentially novel picornavirus species infecting different rodents. Though being most closely related to rosavirus A, rosavirus B and C possessed distinct protease cleavage sites and variations in Yn-Xm-AUG sequence in 5’UTR and myristylation site in VP4. Anti-rosavirus B VP1 antibodies were detected in Norway rats, whereas anti-rosavirus C VP1 and neutralizing antibodies were detected in Indochinese forest rats and Coxing's white-bellied rats. While the highest prevalence was observed in Coxing's white-bellied rats by RT-PCR, the detection of rosavirus C from different rat species suggests potential interspecies transmission. Rosavirus C isolated from 3T3 cells causes multisystemic diseases in a mouse model, with high viral loads and positive viral antigen expression in organs of infected mice after oral or intracerebral inoculation. Histological examination revealed alveolar fluid exudation, interstitial infiltration, alveolar fluid exudate and wall thickening in lungs, and hepatocyte degeneration and lymphocytic/monocytic inflammatory infiltrates with giant cell formation in liver sections of sacrificed mice. Since rosavirus A2 has been detected in fecal samples of children, further studies should elucidate the pathogenicity and emergence potential of different rosaviruses.",2016 Oct 13,"['Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Li, Kenneth S. M.', 'Zhang, Hao-Ji', 'Fan, Rachel Y. Y.', 'Zhang, Anna J. X.', 'Chan, Brandon C. C.', 'Lam, Carol S. F.', 'Yip, Cyril C. Y.', 'Yuen, Ming-Chi', 'Chan, Kwok-Hung', 'Chen, Zhi-Wei', 'Yuen, Kwok-Yung']",PLoS Pathog,,,True
83ee38f0c4d9191d4f6cad59de96a20a50c18417,PMC,Complete Genome Sequence of a Brazil-Type Avian coronavirus Detected in a Chicken,http://dx.doi.org/10.1128/genomeA.01135-16,PMC5064116,27738043,CC BY,"Avian coronavirus is the causative agent of infectious bronchitis in chickens, leading to multisystemic disease that might be controlled if adequate vaccine strains are used. This paper reports the first complete genome sequence of a Brazil type of this virus (27,615 nucleotides [nt]) isolated from the kidneys of a chicken.",2016 Oct 13,"['Brandão, Paulo E.', 'Ayres, Giselle R. R.', 'Torres, Carolina A.', 'Villarreal, Laura Y. B.', 'Hora, Aline S.', 'Taniwaki, Sueli A.']",Genome Announc,,,True
6c4acd1676d614bf6b2e4fdf9d17337e237d440d,PMC,Respiratory Illness and Allergy Related to Work and Home Environment among Commercial Pilots,http://dx.doi.org/10.1371/journal.pone.0164954,PMC5065138,27741314,CC BY,"The aim was to study associations between work and home environment and prevalence and incidence of respiratory health and a history of atopy in a 3-y cohort of commercial pilots. A questionnaire was mailed in 1997 to all pilots in a Scandinavian airline company (N = 622); 577 (93%) participated. The same questionnaire was sent to the participants 3 years later, 436 participated (76%). There were questions on asthma, respiratory symptoms and infections, allergies, the cabin environment, psychosocial environment and the home environment. Associations were analyzed by multiple logistic regression, calculating odds ratios (OR) with 95% confidence intervals (95%CI). The incidence of doctors’ diagnosed asthma and atopy were 2.4 and 16.6 per 1000 person years, respectively. Pilots changing type of flight during follow-up got more airway infections (OR = 11.27; 95% CI 2.39–53.14). Those reporting decreased work control (OR = 1.85; 95% CI 1.03–3.31 for 1 unit change) and those with environmental tobacco smoke (ETS) at home (OR = 3.73; 95% CI 1.09–12.83) had a higher incidence of atopy during follow up. Dampness or mould at home was associated with a higher prevalence of asthma symptoms (OR = 3.55; 95% CI 1.43–8.82) and airway infections (OR = 3.12 95% CI 1.27–7.68). Window pane condensation in winter at home, reported at baseline, was associated with increased incidence of asthma symptoms (OR = 4.14; 95% CI 1.32–12.97) and pilots living in newer buildings at baseline had a higher incidence of airway infections (OR = 5.23; 95% CI 1.43–19.10). In conclusion, lack of work control and ETS at home can be a risk factors for development of allergic symptoms in pilots. Window pane condensation at home can be a risk factor for incidence of asthma symptoms. Dampness and mould at home can be a risk factor for prevalence of asthma symptoms and airway infections and living in newer buildings can be a risk factor for incidence of airway infections.",2016 Oct 14,"['Fu, Xi', 'Lindgren, Torsten', 'Wieslander, Gunilla', 'Janson, Christer', 'Norbäck, Dan']",PLoS One,,,True
e99a0adb1aa26558acfc74fa0c7197a8a591b6ef,PMC,Pathogenicity of a TW-Like Strain of Infectious Bronchitis Virus and Evaluation of the Protection Induced against It by a QX-Like Strain,http://dx.doi.org/10.3389/fmicb.2016.01653,PMC5067408,27803698,CC BY,"Avian infectious bronchitis, a highly contagious disease caused by avian infectious bronchitis virus (IBV), is of considerable economic importance to the poultry industry. New IBV TW-like strains have increasingly emerged in China in recent years; hence, evaluating their pathogenicity and developing a specific vaccine to guard against their potential threat to the poultry industry is important. Here, we examined the pathogenicity of a TW-like IBV strain (GD), and evaluated the protective efficacy of the QX-like strain (JS) against GD in challenge infections in chickens. The results revealed that strain-GD-infected birds experienced severe respiratory signs, renal lesions, and 30–40% mortality. The GD virus had extensive tissue tropism, especially in the trachea, lungs, kidneys, and bursa of Fabricius, and was continuously shed via the respiratory tract and cloaca. The QX-like IBV strain JS is able to completely protect chickens from challenge with the TW-like IBV GD field strain, with no clinical signs or gross lesions, decreased tissue replication rates, lower ciliostasis score, and reduced virus shedding. These findings indicate that IBV GD is highly virulent, and that QX-like JS may serve as an effective vaccine against the threat posed by IBV TW-like viruses.",2016 Oct 18,"['Yan, Shi-hong', 'Chen, Yang', 'Zhao, Jing', 'Xu, Gang', 'Zhao, Ye', 'Zhang, Guo-zhong']",Front Microbiol,,,True
4315ae43f201739bb56193e328dfdbd8a6646b4b,PMC,A Disintegrin and Metalloprotease 17 in the Cardiovascular and Central Nervous Systems,http://dx.doi.org/10.3389/fphys.2016.00469,PMC5067531,27803674,CC BY,"ADAM17 is a metalloprotease and disintegrin that lodges in the plasmatic membrane of several cell types and is able to cleave a wide variety of cell surface proteins. It is somatically expressed in mammalian organisms and its proteolytic action influences several physiological and pathological processes. This review focuses on the structure of ADAM17, its signaling in the cardiovascular system and its participation in certain disorders involving the heart, blood vessels, and neural regulation of autonomic and cardiovascular modulation.",2016 Oct 18,"['Xu, Jiaxi', 'Mukerjee, Snigdha', 'Silva-Alves, Cristiane R. A.', 'Carvalho-Galvão, Alynne', 'Cruz, Josiane C.', 'Balarini, Camille M.', 'Braga, Valdir A.', 'Lazartigues, Eric', 'França-Silva, Maria S.']",Front Physiol,,,True
5e1e254fc92ef00d3a23ebaab664289a8a58c88a,PMC,Viral fusion efficacy of specific H3N2 influenza virus reassortant combinations at single-particle level,http://dx.doi.org/10.1038/srep35537,PMC5067655,27752100,CC BY,"Virus pseudotyping is a useful and safe technique for studying entry of emerging strains of influenza virus. However, few studies have compared different reassortant combinations in pseudoparticle systems, or compared entry kinetics of native viruses and their pseudotyped analogs. Here, vesicular stomatitis virus (VSV)-based pseudovirions displaying distinct influenza virus envelope proteins were tested for fusion activity. We produced VSV pseudotypes containing the prototypical X-31 (H3) HA, either alone or with strain-matched or mismatched N2 NAs. We performed single-particle fusion assays using total internal reflection fluorescence microscopy to compare hemifusion kinetics among these pairings. Results illustrate that matching pseudoparticles behaved very similarly to native virus. Pseudoparticles harboring mismatched HA-NA pairings fuse at significantly slower rates than native virus, and NA-lacking pseudoparticles exhibiting the slowest fusion rates. Relative viral membrane HA density of matching pseudoparticles was higher than in mismatching or NA-lacking pseudoparticles. An equivalent trend of HA expression level on cell membranes of HA/NA co-transfected cells was observed and intracellular trafficking of HA was affected by NA co-expression. Overall, we show that specific influenza HA-NA combinations can profoundly affect the critical role played by HA during entry, which may factor into viral fitness and the emergence of new pandemic influenza viruses.",2016 Oct 18,"['Hsu, Hung-Lun', 'Millet, Jean K.', 'Costello, Deirdre A.', 'Whittaker, Gary R.', 'Daniel, Susan']",Sci Rep,,,True
d106a3d8a3290e403a4b0d22c22698e3d609809d,PMC,Day-to-Day Population Movement and the Management of Dengue Epidemics,http://dx.doi.org/10.1007/s11538-016-0209-6,PMC5069346,27704330,CC BY,"Dengue is a growing public health problem in tropical and subtropical cities. It is transmitted by mosquitoes, and the main strategy for epidemic prevention and control is insecticide fumigation. Effective management is, however, proving elusive. People’s day-to-day movement about the city is believed to be an important factor in the epidemiological dynamics. We use a simple model to examine the fundamental roles of broad demographic and spatial structures in epidemic initiation, growth and control. We show that the key factors are local dilution, characterised by the vector–host ratio, and spatial connectivity, characterised by the extent of habitually variable movement patterns. Epidemic risk in the population is driven by the demographic groups that frequent the areas with the highest vector–host ratio, even if they only spend some of their time there. Synchronisation of epidemic trajectories in different demographic groups is governed by the vector–host ratios to which they are exposed and the strength of connectivity. Strategies for epidemic prevention and management may be made more effective if they take into account the fluctuating landscape of transmission intensity associated with spatial heterogeneity in the vector–host ratio and people’s day-to-day movement patterns. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11538-016-0209-6) contains supplementary material, which is available to authorized users.",2016 Oct 4,"['Falcón-Lezama, Jorge A.', 'Martínez-Vega, Ruth A.', 'Kuri-Morales, Pablo A.', 'Ramos-Castañeda, José', 'Adams, Ben']",Bull Math Biol,,,False
5c5236506e7dfce0f35caf94d9eec62c5b815d0d,PMC,Day-to-Day Population Movement and the Management of Dengue Epidemics,http://dx.doi.org/10.1007/s11538-016-0209-6,PMC5069346,27704330,CC BY,"Dengue is a growing public health problem in tropical and subtropical cities. It is transmitted by mosquitoes, and the main strategy for epidemic prevention and control is insecticide fumigation. Effective management is, however, proving elusive. People’s day-to-day movement about the city is believed to be an important factor in the epidemiological dynamics. We use a simple model to examine the fundamental roles of broad demographic and spatial structures in epidemic initiation, growth and control. We show that the key factors are local dilution, characterised by the vector–host ratio, and spatial connectivity, characterised by the extent of habitually variable movement patterns. Epidemic risk in the population is driven by the demographic groups that frequent the areas with the highest vector–host ratio, even if they only spend some of their time there. Synchronisation of epidemic trajectories in different demographic groups is governed by the vector–host ratios to which they are exposed and the strength of connectivity. Strategies for epidemic prevention and management may be made more effective if they take into account the fluctuating landscape of transmission intensity associated with spatial heterogeneity in the vector–host ratio and people’s day-to-day movement patterns. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11538-016-0209-6) contains supplementary material, which is available to authorized users.",2016 Oct 4,"['Falcón-Lezama, Jorge A.', 'Martínez-Vega, Ruth A.', 'Kuri-Morales, Pablo A.', 'Ramos-Castañeda, José', 'Adams, Ben']",Bull Math Biol,,,True
dfc76bec0889529fc8cfd5075db5b638ee8cefbc,PMC,Gene-expression reversal of lncRNAs and associated mRNAs expression in active vs latent HIV infection,http://dx.doi.org/10.1038/srep34862,PMC5069461,27756902,CC BY,"Interplay between lncRNAs and mRNAs is rapidly emerging as a key epigenetic mechanism in controlling various cell functions. HIV can actively infect and/or can persist latently for years by manipulating host epigenetics; however, its molecular essence remains undiscovered in entirety. Here for the first time, we delineate the influence of HIV on global lncRNAs expression in monocytic cells lines. Our analysis revealed the expression modulation of nearly 1060 such lncRNAs which are associated with differentially expressed mRNAs in active and latent infection. This suggests a greater role of lncRNAs in regulating transcriptional and post-transcriptional gene expression during HIV infection. The differentially expressed mRNAs were involved in several different biological pathways where immunological networks were most enriched. Importantly, we discovered that HIV induces expression reversal of more than 150 lncRNAs between its active and latent infection. Also, hundreds of unique lncRNAs were identified in both infection conditions. The pathology specific “gene-expression reversal” and “on-and-off” switching of lncRNAs and associated mRNAs may lead to establish the relationship between active and HIV infection.",2016 Oct 19,"['Nair, Madhavan', 'Sagar, Vidya', 'Pilakka-Kanthikeel, Sudheesh']",Sci Rep,,,True
7639ac8f8d44510f623a49b4154324b51b0d07fd,PMC,Gene-expression reversal of lncRNAs and associated mRNAs expression in active vs latent HIV infection,http://dx.doi.org/10.1038/srep34862,PMC5069461,27756902,CC BY,"Interplay between lncRNAs and mRNAs is rapidly emerging as a key epigenetic mechanism in controlling various cell functions. HIV can actively infect and/or can persist latently for years by manipulating host epigenetics; however, its molecular essence remains undiscovered in entirety. Here for the first time, we delineate the influence of HIV on global lncRNAs expression in monocytic cells lines. Our analysis revealed the expression modulation of nearly 1060 such lncRNAs which are associated with differentially expressed mRNAs in active and latent infection. This suggests a greater role of lncRNAs in regulating transcriptional and post-transcriptional gene expression during HIV infection. The differentially expressed mRNAs were involved in several different biological pathways where immunological networks were most enriched. Importantly, we discovered that HIV induces expression reversal of more than 150 lncRNAs between its active and latent infection. Also, hundreds of unique lncRNAs were identified in both infection conditions. The pathology specific “gene-expression reversal” and “on-and-off” switching of lncRNAs and associated mRNAs may lead to establish the relationship between active and HIV infection.",2016 Oct 19,"['Nair, Madhavan', 'Sagar, Vidya', 'Pilakka-Kanthikeel, Sudheesh']",Sci Rep,,,False
7694cd45d861b0363acf826f1ccb83b0f5a40e4c,PMC,"MPLEx: a Robust and Universal Protocol for Single-Sample Integrative Proteomic, Metabolomic, and Lipidomic Analyses",http://dx.doi.org/10.1128/mSystems.00043-16,PMC5069757,27822525,CC BY,"Integrative multi-omics analyses can empower more effective investigation and complete understanding of complex biological systems. Despite recent advances in a range of omics analyses, multi-omic measurements of the same sample are still challenging and current methods have not been well evaluated in terms of reproducibility and broad applicability. Here we adapted a solvent-based method, widely applied for extracting lipids and metabolites, to add proteomics to mass spectrometry-based multi-omics measurements. The metabolite, protein, and lipid extraction (MPLEx) protocol proved to be robust and applicable to a diverse set of sample types, including cell cultures, microbial communities, and tissues. To illustrate the utility of this protocol, an integrative multi-omics analysis was performed using a lung epithelial cell line infected with Middle East respiratory syndrome coronavirus, which showed the impact of this virus on the host glycolytic pathway and also suggested a role for lipids during infection. The MPLEx method is a simple, fast, and robust protocol that can be applied for integrative multi-omic measurements from diverse sample types (e.g., environmental, in vitro, and clinical). IMPORTANCE In systems biology studies, the integration of multiple omics measurements (i.e., genomics, transcriptomics, proteomics, metabolomics, and lipidomics) has been shown to provide a more complete and informative view of biological pathways. Thus, the prospect of extracting different types of molecules (e.g., DNAs, RNAs, proteins, and metabolites) and performing multiple omics measurements on single samples is very attractive, but such studies are challenging due to the fact that the extraction conditions differ according to the molecule type. Here, we adapted an organic solvent-based extraction method that demonstrated broad applicability and robustness, which enabled comprehensive proteomics, metabolomics, and lipidomics analyses from the same sample. Author Video: An author video summary of this article is available.",2016 May 10,"['Nakayasu, Ernesto S.', 'Nicora, Carrie D.', 'Sims, Amy C.', 'Burnum-Johnson, Kristin E.', 'Kim, Young-Mo', 'Kyle, Jennifer E.', 'Matzke, Melissa M.', 'Shukla, Anil K.', 'Chu, Rosalie K.', 'Schepmoes, Athena A.', 'Jacobs, Jon M.', 'Baric, Ralph S.', 'Webb-Robertson, Bobbie-Jo', 'Smith, Richard D.', 'Metz, Thomas O.']",mSystems,,,True
ad724f7660b9d84da71a1855f411b5a450aa309e,PMC,A Universal Next-Generation Sequencing Protocol To Generate Noninfectious Barcoded cDNA Libraries from High-Containment RNA Viruses,http://dx.doi.org/10.1128/mSystems.00039-15,PMC5069770,27822536,CC BY,"Several biosafety level 3 and/or 4 (BSL-3/4) pathogens are high-consequence, single-stranded RNA viruses, and their genomes, when introduced into permissive cells, are infectious. Moreover, many of these viruses are select agents (SAs), and their genomes are also considered SAs. For this reason, cDNAs and/or their derivatives must be tested to ensure the absence of infectious virus and/or viral RNA before transfer out of the BSL-3/4 and/or SA laboratory. This tremendously limits the capacity to conduct viral genomic research, particularly the application of next-generation sequencing (NGS). Here, we present a sequence-independent method to rapidly amplify viral genomic RNA while simultaneously abolishing both viral and genomic RNA infectivity across multiple single-stranded positive-sense RNA (ssRNA+) virus families. The process generates barcoded DNA amplicons that range in length from 300 to 1,000 bp, which cannot be used to rescue a virus and are stable to transport at room temperature. Our barcoding approach allows for up to 288 barcoded samples to be pooled into a single library and run across various NGS platforms without potential reconstitution of the viral genome. Our data demonstrate that this approach provides full-length genomic sequence information not only from high-titer virion preparations but it can also recover specific viral sequence from samples with limited starting material in the background of cellular RNA, and it can be used to identify pathogens from unknown samples. In summary, we describe a rapid, universal standard operating procedure that generates high-quality NGS libraries free of infectious virus and infectious viral RNA. IMPORTANCE This report establishes and validates a standard operating procedure (SOP) for select agents (SAs) and other biosafety level 3 and/or 4 (BSL-3/4) RNA viruses to rapidly generate noninfectious, barcoded cDNA amenable for next-generation sequencing (NGS). This eliminates the burden of testing all processed samples derived from high-consequence pathogens prior to transfer from high-containment laboratories to lower-containment facilities for sequencing. Our established protocol can be scaled up for high-throughput sequencing of hundreds of samples simultaneously, which can dramatically reduce the cost and effort required for NGS library construction. NGS data from this SOP can provide complete genome coverage from viral stocks and can also detect virus-specific reads from limited starting material. Our data suggest that the procedure can be implemented and easily validated by institutional biosafety committees across research laboratories.",2016 Jun 7,"['Moser, Lindsey A.', 'Ramirez-Carvajal, Lisbeth', 'Puri, Vinita', 'Pauszek, Steven J.', 'Matthews, Krystal', 'Dilley, Kari A.', 'Mullan, Clancy', 'McGraw, Jennifer', 'Khayat, Michael', 'Beeri, Karen', 'Yee, Anthony', 'Dugan, Vivien', 'Heise, Mark T.', 'Frieman, Matthew B.', 'Rodriguez, Luis L.', 'Bernard, Kristen A.', 'Wentworth, David E.', 'Stockwell, Timothy B.', 'Shabman, Reed S.']",mSystems,,,True
4350c7bc82bb4dba102fe29a6b50ed632b28a920,PMC,What Have We Learned about the Microbiomes of Indoor Environments?,http://dx.doi.org/10.1128/mSystems.00083-16,PMC5069963,27822547,CC BY,"The advent and application of high-throughput molecular techniques for analyzing microbial communities in the indoor environment have led to illuminating findings and are beginning to change the way we think about human health in relation to the built environment. Here I review recent studies on the microbiology of the built environment, organize their findings into 12 major thematic categories, and comment on how these studies have or have not advanced knowledge in each area beyond what we already knew from over 100 years of applying culture-based methods to building samples. I propose that while we have added tremendous complexity to the rich existing knowledge base, the practical implications of this added complexity remain somewhat elusive. It remains to be seen how this new knowledge base will change how we design, build, and operate buildings. Much more research is needed to better understand the complexity with which indoor microbiomes may affect human health in both positive and negative ways.",2016 Jul 26,"Stephens, Brent",mSystems,,,True
92f5ed730f359773e8b3af4bca2d6d6b9cc224c9,PMC,A quasi-experimental study to determine the effects of a multifaceted educational intervention on hand hygiene compliance in a radiography unit,http://dx.doi.org/10.1186/s13756-016-0133-4,PMC5070356,27777757,CC BY,"BACKGROUND: Whilst numerous studies have investigated nurses’ compliance with hand hygiene and use of alcohol-based hand rub (ABHR), limited attention has been paid to these issues in allied health staff. Reports have linked infections to breaches in infection control in the radiography unit (RU). With advances in medical imaging, a higher proportion of patients come into contact with RU staff increasing the need for good hand hygiene compliance. This study aimed to evaluate effectiveness on compliance of an intervention to improve awareness of hand hygiene in the RU of a district hospital. METHODS: A quasi-experimental study design including questionnaires assessing knowledge and attitudes of hand hygiene and direct observation of participants was used to evaluate an educational programme on hand hygiene of the RU of a large district hospital. All healthcare workers (HCW), comprising 76 radiographers, 17 nurses, and nine healthcare assistants (HCA), agreed to participate in the study. Of these, 85 completed the initial and 76 the post-test anonymous questionnaire. The hand hygiene compliance of all 102 HCW was observed over a 3-week period prior to and after the intervention. The 2-month intervention consisted of talks on hand hygiene and benefits of ABHR, provision of visual aids, wall-mounted ABHR dispensers, and personal bottles of ABHR. RESULTS: Before the intervention, overall hand hygiene compliance was low (28.9 %). Post-intervention, compliance with hand hygiene increased to 51.4 %. This improvement was significant for radiographers and HCA. Additionally, knowledge and attitudes improved in particular, understanding that ABHR can largely replace handwashing and there is a need to perform hand hygiene after environmental contact. The increased use of ABHR allowed HCW to feel they had enough time to perform hand hygiene. CONCLUSIONS: The educational intervention led to increased awareness of hand hygiene opportunities and better acceptance of ABHR use. The reduced time needed to perform hand rubbing and improved access to dispensers resulted in fewer missed opportunities. Although radiographers and other allied HCW make frequent contact with patients, these may be mistakenly construed as irrelevant with respect to healthcare associated infections. Stronger emphasis on hand hygiene compliance of these staff may help reduce infection risk.",2016 Oct 19,"['O’Donoghue, Margaret', 'Ng, Suk-Hing', 'Suen, Lorna KP', 'Boost, Maureen']",Antimicrob Resist Infect Control,,,True
c25889c8a5469237f3437394d9c595f9af0c7c4c,PMC,Identification of Aedes aegypti Long Intergenic Non-coding RNAs and Their Association with Wolbachia and Dengue Virus Infection,http://dx.doi.org/10.1371/journal.pntd.0005069,PMC5070814,27760142,CC BY,"Long intergenic non-coding RNAs (lincRNAs) are appearing as an important class of regulatory RNAs with a variety of biological functions. The aim of this study was to identify the lincRNA profile in the dengue vector Aedes aegypti and evaluate their potential role in host-pathogen interaction. The majority of previous RNA-Seq transcriptome studies in Ae. aegypti have focused on the expression pattern of annotated protein coding genes under different biological conditions. Here, we used 35 publically available RNA-Seq datasets with relatively high depth to screen the Ae. aegypti genome for lincRNA discovery. This led to the identification of 3,482 putative lincRNAs. These lincRNA genes displayed a slightly lower GC content and shorter transcript lengths compared to protein-encoding genes. Ae. aegypti lincRNAs also demonstrate low evolutionary sequence conservation even among closely related species such as Culex quinquefasciatus and Anopheles gambiae. We examined their expression in dengue virus serotype 2 (DENV-2) and Wolbachia infected and non-infected adult mosquitoes and Aa20 cells. The results revealed that DENV-2 infection increased the abundance of a number of host lincRNAs, from which some suppress viral replication in mosquito cells. RNAi-mediated silencing of lincRNA_1317 led to enhancement in viral replication, which possibly indicates its potential involvement in the host anti-viral defense. A number of lincRNAs were also differentially expressed in Wolbachia-infected mosquitoes. The results will facilitate future studies to unravel the function of lncRNAs in insects and may prove to be beneficial in developing new ways to control vectors or inhibit replication of viruses in them.",2016 Oct 19,"['Etebari, Kayvan', 'Asad, Sultan', 'Zhang, Guangmei', 'Asgari, Sassan']",PLoS Negl Trop Dis,,,True
ac1e0c34f47a58c5d830bd63399b3400cab8375d,PMC,Characterization of the Role of Hexamer AGUAAA and Poly(A) Tail in Coronavirus Polyadenylation,http://dx.doi.org/10.1371/journal.pone.0165077,PMC5070815,27760233,CC BY,"Similar to eukaryotic mRNA, the positive-strand coronavirus genome of ~30 kilobases is 5’-capped and 3’-polyadenylated. It has been demonstrated that the length of the coronaviral poly(A) tail is not static but regulated during infection; however, little is known regarding the factors involved in coronaviral polyadenylation and its regulation. Here, we show that during infection, the level of coronavirus poly(A) tail lengthening depends on the initial length upon infection and that the minimum length to initiate lengthening may lie between 5 and 9 nucleotides. By mutagenesis analysis, it was found that (i) the hexamer AGUAAA and poly(A) tail are two important elements responsible for synthesis of the coronavirus poly(A) tail and may function in concert to accomplish polyadenylation and (ii) the function of the hexamer AGUAAA in coronaviral polyadenylation is position dependent. Based on these findings, we propose a process for how the coronaviral poly(A) tail is synthesized and undergoes variation. Our results provide the first genetic evidence to gain insight into coronaviral polyadenylation.",2016 Oct 19,"['Peng, Yu-Hui', 'Lin, Ching-Houng', 'Lin, Chao-Nan', 'Lo, Chen-Yu', 'Tsai, Tsung-Lin', 'Wu, Hung-Yi']",PLoS One,,,True
60af5c4467ebb43ff79857a9c515e625d4aa3aa9,PMC,Cryo-electron Microscopy Analysis of Structurally Heterogeneous Macromolecular Complexes,http://dx.doi.org/10.1016/j.csbj.2016.10.002,PMC5072154,27800126,CC BY,"Cryo-electron microscopy (cryo-EM) has for a long time been a technique of choice for determining structure of large and flexible macromolecular complexes that were difficult to study by other experimental techniques such as X-ray crystallography or nuclear magnetic resonance. However, a fast development of instruments and software for cryo-EM in the last decade has allowed that a large range of complexes can be studied by cryo-EM, and that their structures can be obtained at near-atomic resolution, including the structures of small complexes (e.g., membrane proteins) whose size was earlier an obstacle to cryo-EM. Image analysis to identify multiple coexisting structures in the same specimen (multiconformation reconstruction) is now routinely done both to solve structures at near-atomic resolution and to study conformational dynamics. Methods for multiconformation reconstruction and latest examples of their applications are the focus of this review.",2016 Oct 14,"Jonić, Slavica",Comput Struct Biotechnol J,,,False
188a2e1351ceae0aa8347e1a1d7af1e3b7b66a02,PMC,Epidemiology and Clinical Presentations of Respiratory Syncytial Virus Subgroups A and B Detected with Multiplex Real-Time PCR,http://dx.doi.org/10.1371/journal.pone.0165108,PMC5072546,27764220,CC BY,"Respiratory syncytial virus (RSV) is one of the most important pathogenic infections of children and requires in-depth research worldwide, and especially in developing countries. We used a novel multiplex real-time PCR to test 5483 patients (≤ 14 years old) hospitalized with respiratory illness in Guangzhou, China, over a 3-year period. Of these patients, 729 were positive for RSV-A (51.2%, 373/729) or RSV-B (48.8%, 356/729), but none was infected with both viruses. Two seasonal peaks in total RSV were detected at the changes from winter to spring and from summer to autumn. RSV-B was dominant in 2013 and RSV-A in 2015, whereas RSV-A and RSV-B cocirculated in 2014. The clinical presentations of 645 RSV-positive patients were analyzed. Bronchiolitis, dyspnea, coryza, vomiting, poor appetite, and diarrhea occurred more frequently in RSV-A-positive than RSV-B-positive patients, whereas chill, headache, myalgia, debility, and rash etc. were more frequent in RSV-B-positive than RSV-A-positive patients, suggesting specific clinical characteristics for RSV-A and RSV-B. Coinfectons with other pathogens were common and diverse. Bronchiolitis, fever (≥ 38°C), and poor appetite were more frequent in patients with single RSV infections than in coinfected patients, suggesting the key pathogenic activity of RSV. Analysis of the relationships between the comparative viral load and clinical presentations showed significant differences in bronchiolitis, fever (≥ 38°C), and rash etc. among patients with different viral loads. This study provides a novel rapid method for detecting RSV subgroups, and provides new insights into the epidemiology and clinical implications of RSV.",2016 Oct 20,"['Liu, Wenkuan', 'Chen, Dehui', 'Tan, Weiping', 'Xu, Duo', 'Qiu, Shuyan', 'Zeng, Zhiqi', 'Li, Xiao', 'Zhou, Rong']",PLoS One,,,True
cbabbd687725e949c99a0a6f53f033128ea1aaca,PMC,Precisely Molded Nanoparticle Displaying DENV-E Proteins Induces Robust Serotype-Specific Neutralizing Antibody Responses,http://dx.doi.org/10.1371/journal.pntd.0005071,PMC5072622,27764114,CC BY,"Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year. Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes. Instead of using whole-virus formulations, we are exploring the potentials for a particulate subunit vaccine, based on DENV E-protein displayed on nanoparticles that have been precisely molded using Particle Replication in Non-wetting Template (PRINT) technology. Here we describe immunization studies with a DENV2-nanoparticle vaccine candidate. The ectodomain of DENV2-E protein was expressed as a secreted recombinant protein (sRecE), purified and adsorbed to poly (lactic-co-glycolic acid) (PLGA) nanoparticles of different sizes and shape. We show that PRINT nanoparticle adsorbed sRecE without any adjuvant induces higher IgG titers and a more potent DENV2-specific neutralizing antibody response compared to the soluble sRecE protein alone. Antigen trafficking indicate that PRINT nanoparticle display of sRecE prolongs the bio-availability of the antigen in the draining lymph nodes by creating an antigen depot. Our results demonstrate that PRINT nanoparticles are a promising platform for delivering subunit vaccines against flaviviruses such as dengue and Zika.",2016 Oct 20,"['Metz, Stefan W.', 'Tian, Shaomin', 'Hoekstra, Gabriel', 'Yi, Xianwen', 'Stone, Michelle', 'Horvath, Katie', 'Miley, Michael J.', 'DeSimone, Joseph', 'Luft, Chris J.', 'de Silva, Aravinda M.']",PLoS Negl Trop Dis,,,True
11ccc8d0c6d5b3297821a0e39535ce9dcb4810ef,PMC,A Meta-Analysis of the Association between Gender and Protective Behaviors in Response to Respiratory Epidemics and Pandemics,http://dx.doi.org/10.1371/journal.pone.0164541,PMC5074573,27768704,CC0,"Respiratory infectious disease epidemics and pandemics are recurring events that levy a high cost on individuals and society. The health-protective behavioral response of the public plays an important role in limiting respiratory infectious disease spread. Health-protective behaviors take several forms. Behaviors can be categorized as pharmaceutical (e.g., vaccination uptake, antiviral use) or non-pharmaceutical (e.g., hand washing, face mask use, avoidance of public transport). Due to the limitations of pharmaceutical interventions during respiratory epidemics and pandemics, public health campaigns aimed at limiting disease spread often emphasize both non-pharmaceutical and pharmaceutical behavioral interventions. Understanding the determinants of the public’s behavioral response is crucial for devising public health campaigns, providing information to parametrize mathematical models, and ultimately limiting disease spread. While other reviews have qualitatively analyzed the body of work on demographic determinants of health-protective behavior, this meta-analysis quantitatively combines the results from 85 publications to determine the global relationship between gender and health-protective behavioral response. The results show that women in the general population are about 50% more likely than men to adopt/practice non-pharmaceutical behaviors. Conversely, men in the general population are marginally (about 12%) more likely than women to adopt/practice pharmaceutical behaviors. It is possible that factors other than pharmaceutical/non-pharmaceutical status not included in this analysis act as moderators of this relationship. These results suggest an inherent difference in how men and women respond to epidemic and pandemic respiratory infectious diseases. This information can be used to target specific groups when developing non-pharmaceutical public health campaigns and to parameterize epidemic models incorporating demographic information.",2016 Oct 21,"['Moran, Kelly R.', 'Del Valle, Sara Y.']",PLoS One,,,True
70f13cba6028d0822b98cc2d8e5bd221ea8d4e16,PMC,A Meta-Analysis of the Association between Gender and Protective Behaviors in Response to Respiratory Epidemics and Pandemics,http://dx.doi.org/10.1371/journal.pone.0164541,PMC5074573,27768704,CC0,"Respiratory infectious disease epidemics and pandemics are recurring events that levy a high cost on individuals and society. The health-protective behavioral response of the public plays an important role in limiting respiratory infectious disease spread. Health-protective behaviors take several forms. Behaviors can be categorized as pharmaceutical (e.g., vaccination uptake, antiviral use) or non-pharmaceutical (e.g., hand washing, face mask use, avoidance of public transport). Due to the limitations of pharmaceutical interventions during respiratory epidemics and pandemics, public health campaigns aimed at limiting disease spread often emphasize both non-pharmaceutical and pharmaceutical behavioral interventions. Understanding the determinants of the public’s behavioral response is crucial for devising public health campaigns, providing information to parametrize mathematical models, and ultimately limiting disease spread. While other reviews have qualitatively analyzed the body of work on demographic determinants of health-protective behavior, this meta-analysis quantitatively combines the results from 85 publications to determine the global relationship between gender and health-protective behavioral response. The results show that women in the general population are about 50% more likely than men to adopt/practice non-pharmaceutical behaviors. Conversely, men in the general population are marginally (about 12%) more likely than women to adopt/practice pharmaceutical behaviors. It is possible that factors other than pharmaceutical/non-pharmaceutical status not included in this analysis act as moderators of this relationship. These results suggest an inherent difference in how men and women respond to epidemic and pandemic respiratory infectious diseases. This information can be used to target specific groups when developing non-pharmaceutical public health campaigns and to parameterize epidemic models incorporating demographic information.",2016 Oct 21,"['Moran, Kelly R.', 'Del Valle, Sara Y.']",PLoS One,,,False
1440ccd08199d80d52bb2e0e0431f020954709a5,PMC,A Meta-Analysis of the Association between Gender and Protective Behaviors in Response to Respiratory Epidemics and Pandemics,http://dx.doi.org/10.1371/journal.pone.0164541,PMC5074573,27768704,CC0,"Respiratory infectious disease epidemics and pandemics are recurring events that levy a high cost on individuals and society. The health-protective behavioral response of the public plays an important role in limiting respiratory infectious disease spread. Health-protective behaviors take several forms. Behaviors can be categorized as pharmaceutical (e.g., vaccination uptake, antiviral use) or non-pharmaceutical (e.g., hand washing, face mask use, avoidance of public transport). Due to the limitations of pharmaceutical interventions during respiratory epidemics and pandemics, public health campaigns aimed at limiting disease spread often emphasize both non-pharmaceutical and pharmaceutical behavioral interventions. Understanding the determinants of the public’s behavioral response is crucial for devising public health campaigns, providing information to parametrize mathematical models, and ultimately limiting disease spread. While other reviews have qualitatively analyzed the body of work on demographic determinants of health-protective behavior, this meta-analysis quantitatively combines the results from 85 publications to determine the global relationship between gender and health-protective behavioral response. The results show that women in the general population are about 50% more likely than men to adopt/practice non-pharmaceutical behaviors. Conversely, men in the general population are marginally (about 12%) more likely than women to adopt/practice pharmaceutical behaviors. It is possible that factors other than pharmaceutical/non-pharmaceutical status not included in this analysis act as moderators of this relationship. These results suggest an inherent difference in how men and women respond to epidemic and pandemic respiratory infectious diseases. This information can be used to target specific groups when developing non-pharmaceutical public health campaigns and to parameterize epidemic models incorporating demographic information.",2016 Oct 21,"['Moran, Kelly R.', 'Del Valle, Sara Y.']",PLoS One,,,False
819d44a58a9c9fcd036cf7bfd4da0eda8f620bb3,PMC,A Meta-Analysis of the Association between Gender and Protective Behaviors in Response to Respiratory Epidemics and Pandemics,http://dx.doi.org/10.1371/journal.pone.0164541,PMC5074573,27768704,CC0,"Respiratory infectious disease epidemics and pandemics are recurring events that levy a high cost on individuals and society. The health-protective behavioral response of the public plays an important role in limiting respiratory infectious disease spread. Health-protective behaviors take several forms. Behaviors can be categorized as pharmaceutical (e.g., vaccination uptake, antiviral use) or non-pharmaceutical (e.g., hand washing, face mask use, avoidance of public transport). Due to the limitations of pharmaceutical interventions during respiratory epidemics and pandemics, public health campaigns aimed at limiting disease spread often emphasize both non-pharmaceutical and pharmaceutical behavioral interventions. Understanding the determinants of the public’s behavioral response is crucial for devising public health campaigns, providing information to parametrize mathematical models, and ultimately limiting disease spread. While other reviews have qualitatively analyzed the body of work on demographic determinants of health-protective behavior, this meta-analysis quantitatively combines the results from 85 publications to determine the global relationship between gender and health-protective behavioral response. The results show that women in the general population are about 50% more likely than men to adopt/practice non-pharmaceutical behaviors. Conversely, men in the general population are marginally (about 12%) more likely than women to adopt/practice pharmaceutical behaviors. It is possible that factors other than pharmaceutical/non-pharmaceutical status not included in this analysis act as moderators of this relationship. These results suggest an inherent difference in how men and women respond to epidemic and pandemic respiratory infectious diseases. This information can be used to target specific groups when developing non-pharmaceutical public health campaigns and to parameterize epidemic models incorporating demographic information.",2016 Oct 21,"['Moran, Kelly R.', 'Del Valle, Sara Y.']",PLoS One,,,False
64b360d629a697bc95ae4dac99059fe91311a795,PMC,A Meta-Analysis of the Association between Gender and Protective Behaviors in Response to Respiratory Epidemics and Pandemics,http://dx.doi.org/10.1371/journal.pone.0164541,PMC5074573,27768704,CC0,"Respiratory infectious disease epidemics and pandemics are recurring events that levy a high cost on individuals and society. The health-protective behavioral response of the public plays an important role in limiting respiratory infectious disease spread. Health-protective behaviors take several forms. Behaviors can be categorized as pharmaceutical (e.g., vaccination uptake, antiviral use) or non-pharmaceutical (e.g., hand washing, face mask use, avoidance of public transport). Due to the limitations of pharmaceutical interventions during respiratory epidemics and pandemics, public health campaigns aimed at limiting disease spread often emphasize both non-pharmaceutical and pharmaceutical behavioral interventions. Understanding the determinants of the public’s behavioral response is crucial for devising public health campaigns, providing information to parametrize mathematical models, and ultimately limiting disease spread. While other reviews have qualitatively analyzed the body of work on demographic determinants of health-protective behavior, this meta-analysis quantitatively combines the results from 85 publications to determine the global relationship between gender and health-protective behavioral response. The results show that women in the general population are about 50% more likely than men to adopt/practice non-pharmaceutical behaviors. Conversely, men in the general population are marginally (about 12%) more likely than women to adopt/practice pharmaceutical behaviors. It is possible that factors other than pharmaceutical/non-pharmaceutical status not included in this analysis act as moderators of this relationship. These results suggest an inherent difference in how men and women respond to epidemic and pandemic respiratory infectious diseases. This information can be used to target specific groups when developing non-pharmaceutical public health campaigns and to parameterize epidemic models incorporating demographic information.",2016 Oct 21,"['Moran, Kelly R.', 'Del Valle, Sara Y.']",PLoS One,,,False
d51a55b2f7c2277e6435f0ecf13569863cc3adf3,PMC,Mechanisms of viral mutation,http://dx.doi.org/10.1007/s00018-016-2299-6,PMC5075021,27392606,CC BY,"The remarkable capacity of some viruses to adapt to new hosts and environments is highly dependent on their ability to generate de novo diversity in a short period of time. Rates of spontaneous mutation vary amply among viruses. RNA viruses mutate faster than DNA viruses, single-stranded viruses mutate faster than double-strand virus, and genome size appears to correlate negatively with mutation rate. Viral mutation rates are modulated at different levels, including polymerase fidelity, sequence context, template secondary structure, cellular microenvironment, replication mechanisms, proofreading, and access to post-replicative repair. Additionally, massive numbers of mutations can be introduced by some virus-encoded diversity-generating elements, as well as by host-encoded cytidine/adenine deaminases. Our current knowledge of viral mutation rates indicates that viral genetic diversity is determined by multiple virus- and host-dependent processes, and that viral mutation rates can evolve in response to specific selective pressures.",2016 Jul 8,"['Sanjuán, Rafael', 'Domingo-Calap, Pilar']",Cell Mol Life Sci,,,True
5d445fbd8aa18aca2c2f7c947b25ddd62533f96b,PMC,"N-Desmethylclozapine, Fluoxetine, and Salmeterol Inhibit Postentry Stages of the Dengue Virus Life Cycle",http://dx.doi.org/10.1128/AAC.01367-16,PMC5075077,27572397,CC BY,"Around 10,000 people die each year due to severe dengue disease, and two-thirds of the world population lives in a region where dengue disease is endemic. There has been remarkable progress in dengue virus vaccine development; however, there are no licensed antivirals for dengue disease, and none appear to be in clinical trials. We took the approach of repositioning approved drugs for anti-dengue virus activity by screening a library of pharmacologically active compounds. We identified N-desmethylclozapine, fluoxetine hydrochloride, and salmeterol xinafoate as dengue virus inhibitors based on reductions in the numbers of infected cells and viral titers. Dengue virus RNA levels were diminished in inhibitor-treated cells, and this effect was specific to dengue virus, as other flaviviruses, such as Japanese encephalitis virus and West Nile virus, or other RNA viruses, such as respiratory syncytial virus and rotavirus, were not affected by these inhibitors. All three inhibitors specifically inhibited dengue virus replication with 50% inhibitory concentrations (IC(50)s) in the high-nanomolar range. Estimation of negative-strand RNA intermediates and time-of-addition experiments indicated that inhibition was occurring at a postentry stage, most probably at the initiation of viral RNA replication. Finally, we show that inhibition is most likely due to the modulation of the endolysosomal pathway and induction of autophagy.",2016 Oct 21,"['Medigeshi, Guruprasad R.', 'Kumar, Rinki', 'Dhamija, Ekta', 'Agrawal, Tanvi', 'Kar, Meenakshi']",Antimicrob Agents Chemother,,,True
4bf5ba8fe5af1bf36c9f2f3af74541fbda3a2c89,PMC,"N-Desmethylclozapine, Fluoxetine, and Salmeterol Inhibit Postentry Stages of the Dengue Virus Life Cycle",http://dx.doi.org/10.1128/AAC.01367-16,PMC5075077,27572397,CC BY,"Around 10,000 people die each year due to severe dengue disease, and two-thirds of the world population lives in a region where dengue disease is endemic. There has been remarkable progress in dengue virus vaccine development; however, there are no licensed antivirals for dengue disease, and none appear to be in clinical trials. We took the approach of repositioning approved drugs for anti-dengue virus activity by screening a library of pharmacologically active compounds. We identified N-desmethylclozapine, fluoxetine hydrochloride, and salmeterol xinafoate as dengue virus inhibitors based on reductions in the numbers of infected cells and viral titers. Dengue virus RNA levels were diminished in inhibitor-treated cells, and this effect was specific to dengue virus, as other flaviviruses, such as Japanese encephalitis virus and West Nile virus, or other RNA viruses, such as respiratory syncytial virus and rotavirus, were not affected by these inhibitors. All three inhibitors specifically inhibited dengue virus replication with 50% inhibitory concentrations (IC(50)s) in the high-nanomolar range. Estimation of negative-strand RNA intermediates and time-of-addition experiments indicated that inhibition was occurring at a postentry stage, most probably at the initiation of viral RNA replication. Finally, we show that inhibition is most likely due to the modulation of the endolysosomal pathway and induction of autophagy.",2016 Oct 21,"['Medigeshi, Guruprasad R.', 'Kumar, Rinki', 'Dhamija, Ekta', 'Agrawal, Tanvi', 'Kar, Meenakshi']",Antimicrob Agents Chemother,,,True
ab128bd5ddc658efa99c3c318f4ccf64c5eaea3b,PMC,Experimental Piscine orthoreovirus infection mediates protection against pancreas disease in Atlantic salmon (Salmo salar),http://dx.doi.org/10.1186/s13567-016-0389-y,PMC5075195,27769313,CC BY,"Viral diseases are among the main challenges in farming of Atlantic salmon (Salmo salar). The most prevalent viral diseases in Norwegian salmon aquaculture are heart and skeletal muscle inflammation (HSMI) caused by Piscine orthoreovirus (PRV), and pancreas disease (PD) caused by Salmonid alphavirus (SAV). Both PRV and SAV target heart and skeletal muscles, but SAV additionally targets exocrine pancreas. PRV and SAV are often present in the same locations and co-infections occur, but the effect of this crosstalk on disease development has not been investigated. In the present experiment, the effect of a primary PRV infection on subsequent SAV infection was studied. Atlantic salmon were infected with PRV by cohabitation, followed by addition of SAV shedder fish 4 or 10 weeks after the initial PRV infection. Histopathological evaluation, monitoring of viral RNA levels and host gene expression analysis were used to assess disease development. Significant reduction of SAV RNA levels and of PD specific histopathological changes were observed in the co-infected groups compared to fish infected by SAV only. A strong correlation was found between histopathological development and expression of disease related genes in heart. In conclusion, experimentally PRV infected salmon are less susceptible to secondary SAV infection and development of PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0389-y) contains supplementary material, which is available to authorized users.",2016 Oct 21,"['Lund, Morten', 'Røsæg, Magnus Vikan', 'Krasnov, Aleksei', 'Timmerhaus, Gerrit', 'Nyman, Ingvild Berg', 'Aspehaug, Vidar', 'Rimstad, Espen', 'Dahle, Maria Krudtaa']",Vet Res,,,False
97828b05cc598211ed632a6d931a13575c7181a6,PMC,Experimental Piscine orthoreovirus infection mediates protection against pancreas disease in Atlantic salmon (Salmo salar),http://dx.doi.org/10.1186/s13567-016-0389-y,PMC5075195,27769313,CC BY,"Viral diseases are among the main challenges in farming of Atlantic salmon (Salmo salar). The most prevalent viral diseases in Norwegian salmon aquaculture are heart and skeletal muscle inflammation (HSMI) caused by Piscine orthoreovirus (PRV), and pancreas disease (PD) caused by Salmonid alphavirus (SAV). Both PRV and SAV target heart and skeletal muscles, but SAV additionally targets exocrine pancreas. PRV and SAV are often present in the same locations and co-infections occur, but the effect of this crosstalk on disease development has not been investigated. In the present experiment, the effect of a primary PRV infection on subsequent SAV infection was studied. Atlantic salmon were infected with PRV by cohabitation, followed by addition of SAV shedder fish 4 or 10 weeks after the initial PRV infection. Histopathological evaluation, monitoring of viral RNA levels and host gene expression analysis were used to assess disease development. Significant reduction of SAV RNA levels and of PD specific histopathological changes were observed in the co-infected groups compared to fish infected by SAV only. A strong correlation was found between histopathological development and expression of disease related genes in heart. In conclusion, experimentally PRV infected salmon are less susceptible to secondary SAV infection and development of PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0389-y) contains supplementary material, which is available to authorized users.",2016 Oct 21,"['Lund, Morten', 'Røsæg, Magnus Vikan', 'Krasnov, Aleksei', 'Timmerhaus, Gerrit', 'Nyman, Ingvild Berg', 'Aspehaug, Vidar', 'Rimstad, Espen', 'Dahle, Maria Krudtaa']",Vet Res,,,False
5c322466f751d5543c600586f1df5db18a2ca2b9,PMC,Experimental Piscine orthoreovirus infection mediates protection against pancreas disease in Atlantic salmon (Salmo salar),http://dx.doi.org/10.1186/s13567-016-0389-y,PMC5075195,27769313,CC BY,"Viral diseases are among the main challenges in farming of Atlantic salmon (Salmo salar). The most prevalent viral diseases in Norwegian salmon aquaculture are heart and skeletal muscle inflammation (HSMI) caused by Piscine orthoreovirus (PRV), and pancreas disease (PD) caused by Salmonid alphavirus (SAV). Both PRV and SAV target heart and skeletal muscles, but SAV additionally targets exocrine pancreas. PRV and SAV are often present in the same locations and co-infections occur, but the effect of this crosstalk on disease development has not been investigated. In the present experiment, the effect of a primary PRV infection on subsequent SAV infection was studied. Atlantic salmon were infected with PRV by cohabitation, followed by addition of SAV shedder fish 4 or 10 weeks after the initial PRV infection. Histopathological evaluation, monitoring of viral RNA levels and host gene expression analysis were used to assess disease development. Significant reduction of SAV RNA levels and of PD specific histopathological changes were observed in the co-infected groups compared to fish infected by SAV only. A strong correlation was found between histopathological development and expression of disease related genes in heart. In conclusion, experimentally PRV infected salmon are less susceptible to secondary SAV infection and development of PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0389-y) contains supplementary material, which is available to authorized users.",2016 Oct 21,"['Lund, Morten', 'Røsæg, Magnus Vikan', 'Krasnov, Aleksei', 'Timmerhaus, Gerrit', 'Nyman, Ingvild Berg', 'Aspehaug, Vidar', 'Rimstad, Espen', 'Dahle, Maria Krudtaa']",Vet Res,,,False
84befea7ee1f85d2e9367d83bdb4834d56f9682a,PMC,Experimental Piscine orthoreovirus infection mediates protection against pancreas disease in Atlantic salmon (Salmo salar),http://dx.doi.org/10.1186/s13567-016-0389-y,PMC5075195,27769313,CC BY,"Viral diseases are among the main challenges in farming of Atlantic salmon (Salmo salar). The most prevalent viral diseases in Norwegian salmon aquaculture are heart and skeletal muscle inflammation (HSMI) caused by Piscine orthoreovirus (PRV), and pancreas disease (PD) caused by Salmonid alphavirus (SAV). Both PRV and SAV target heart and skeletal muscles, but SAV additionally targets exocrine pancreas. PRV and SAV are often present in the same locations and co-infections occur, but the effect of this crosstalk on disease development has not been investigated. In the present experiment, the effect of a primary PRV infection on subsequent SAV infection was studied. Atlantic salmon were infected with PRV by cohabitation, followed by addition of SAV shedder fish 4 or 10 weeks after the initial PRV infection. Histopathological evaluation, monitoring of viral RNA levels and host gene expression analysis were used to assess disease development. Significant reduction of SAV RNA levels and of PD specific histopathological changes were observed in the co-infected groups compared to fish infected by SAV only. A strong correlation was found between histopathological development and expression of disease related genes in heart. In conclusion, experimentally PRV infected salmon are less susceptible to secondary SAV infection and development of PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0389-y) contains supplementary material, which is available to authorized users.",2016 Oct 21,"['Lund, Morten', 'Røsæg, Magnus Vikan', 'Krasnov, Aleksei', 'Timmerhaus, Gerrit', 'Nyman, Ingvild Berg', 'Aspehaug, Vidar', 'Rimstad, Espen', 'Dahle, Maria Krudtaa']",Vet Res,,,True
f071dcbf396ad4171f3984d42f08291385ea9cf7,PMC,"Rapid Detection Strategies for the Global Threat of Zika Virus: Current State, New Hypotheses, and Limitations",http://dx.doi.org/10.3389/fmicb.2016.01685,PMC5075579,27822207,CC BY,"The current scenario regarding the widespread Zika virus (ZIKV) has resulted in numerous diagnostic studies, specifically in South America and in locations where there is frequent entry of travelers returning from ZIKV-affected areas, including pregnant women with or without clinical symptoms of ZIKV infection. The World Health Organization, WHO, announced that millions of cases of ZIKV are likely to occur in the USA in the near future. This situation has created an alarming public health emergency of international concern requiring the detection of this life-threatening viral candidate due to increased cases of newborn microcephaly associated with ZIKV infection. Hence, this review reports possible methods and strategies for the fast and reliable detection of ZIKV with particular emphasis on current updates, knowledge, and new hypotheses that might be helpful for medical professionals in poor and developing countries that urgently need to address this problem. In particular, we emphasize liposome-based biosensors. Although these biosensors are currently among the less popular tools for human disease detection, they have become useful tools for the screening and detection of pathogenic bacteria, fungi, and viruses because of their versatile advantageous features compared to other sensing devices. This review summarizes the currently available methods employed for the rapid detection of ZIKV and suggests an innovative approach involving the application of a liposome-based hypothesis for the development of new strategies for ZIKV detection and their use as effective biomedicinal tools.",2016 Oct 24,"['Shukla, Shruti', 'Hong, Sung-Yong', 'Chung, Soo Hyun', 'Kim, Myunghee']",Front Microbiol,,,True
891be4e9dc60d9b0c9ff79d35e11576ceeb8a592,PMC,Role of Antioxidants and Natural Products in Inflammation,http://dx.doi.org/10.1155/2016/5276130,PMC5075620,27803762,CC BY,"Inflammation is a comprehensive array of physiological response to a foreign organism, including human pathogens, dust particles, and viruses. Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms. Recent investigations have clarified that inflammation is a major factor for the progression of various chronic diseases/disorders, including diabetes, cancer, cardiovascular diseases, eye disorders, arthritis, obesity, autoimmune diseases, and inflammatory bowel disease. Free radical productions from different biological and environmental sources are due to an imbalance of natural antioxidants which further leads to various inflammatory associated diseases. In this review article, we have outlined the inflammatory process and its cellular mechanisms involved in the progression of various chronic modern human diseases. In addition, we have discussed the role of free radicals-induced tissue damage, antioxidant defence, and molecular mechanisms in chronic inflammatory diseases/disorders. The systematic knowledge regarding the role of inflammation and its associated adverse effects can provide a clear understanding in the development of innovative therapeutic targets from natural sources that are intended for suppression of various chronic inflammations associated diseases.",2016 Oct 10,"['Arulselvan, Palanisamy', 'Fard, Masoumeh Tangestani', 'Tan, Woan Sean', 'Gothai, Sivapragasam', 'Fakurazi, Sharida', 'Norhaizan, Mohd Esa', 'Kumar, S. Suresh']",Oxid Med Cell Longev,,,True
b3790b85395ee7e6d6abffce6fdee7ebe6090aac,PMC,"Respiratory microbes present in the nasopharynx of children hospitalised with suspected pulmonary tuberculosis in Cape Town, South Africa",http://dx.doi.org/10.1186/s12879-016-1934-z,PMC5075757,27776489,CC BY,"BACKGROUND: Lower respiratory tract infection in children is increasingly thought to be polymicrobial in origin. Children with symptoms suggestive of pulmonary tuberculosis (PTB) may have tuberculosis, other respiratory tract infections or co-infection with Mycobacterium tuberculosis and other pathogens. We aimed to identify the presence of potential respiratory pathogens in nasopharyngeal (NP) samples from children with suspected PTB. METHOD: NP samples collected from consecutive children presenting with suspected PTB at Red Cross Children’s Hospital (Cape Town, South Africa) were tested by multiplex real-time RT-PCR. Mycobacterial liquid culture and Xpert MTB/RIF was performed on 2 induced sputa obtained from each participant. Children were categorised as definite-TB (culture or qPCR [Xpert MTB/RIF] confirmed), unlikely-TB (improvement of symptoms without TB treatment on follow-up) and unconfirmed-TB (all other children). RESULTS: Amongst 214 children with a median age of 36 months (interquartile range, [IQR] 19–66 months), 34 (16 %) had definite-TB, 86 (40 %) had unconfirmed-TB and 94 (44 %) were classified as unlikely-TB. Moraxella catarrhalis (64 %), Streptococcus pneumoniae (42 %), Haemophilus influenzae spp (29 %) and Staphylococcus aureus (22 %) were the most common bacteria detected in NP samples. Other bacteria detected included Mycoplasma pneumoniae (9 %), Bordetella pertussis (7 %) and Chlamydophila pneumoniae (4 %). The most common viruses detected included metapneumovirus (19 %), rhinovirus (15 %), influenza virus C (9 %), adenovirus (7 %), cytomegalovirus (7 %) and coronavirus O43 (5.6 %). Both bacteria and viruses were detected in 73, 55 and 56 % of the definite, unconfirmed and unlikely-TB groups, respectively. There were no significant differences in the distribution of respiratory microbes between children with and without TB. Using quadratic discriminant analysis, human metapneumovirus, C. pneumoniae, coronavirus 043, influenza virus C virus, rhinovirus and cytomegalovirus best discriminated children with definite-TB from the other groups of children. CONCLUSIONS: A broad range of potential respiratory pathogens was detected in children with suspected TB. There was no clear association between TB categorisation and detection of a specific pathogen. Further work is needed to explore potential pathogen interactions and their role in the pathogenesis of PTB. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1934-z) contains supplementary material, which is available to authorized users.",2016 Oct 24,"['Dube, Felix S.', 'Kaba, Mamadou', 'Robberts, F. J. Lourens', 'Tow, Lemese Ah', 'Lubbe, Sugnet', 'Zar, Heather J.', 'Nicol, Mark P.']",BMC Infect Dis,,,False
4e3d9e4efadec3ac6b84928d59d18992b155d3ea,PMC,"Respiratory microbes present in the nasopharynx of children hospitalised with suspected pulmonary tuberculosis in Cape Town, South Africa",http://dx.doi.org/10.1186/s12879-016-1934-z,PMC5075757,27776489,CC BY,"BACKGROUND: Lower respiratory tract infection in children is increasingly thought to be polymicrobial in origin. Children with symptoms suggestive of pulmonary tuberculosis (PTB) may have tuberculosis, other respiratory tract infections or co-infection with Mycobacterium tuberculosis and other pathogens. We aimed to identify the presence of potential respiratory pathogens in nasopharyngeal (NP) samples from children with suspected PTB. METHOD: NP samples collected from consecutive children presenting with suspected PTB at Red Cross Children’s Hospital (Cape Town, South Africa) were tested by multiplex real-time RT-PCR. Mycobacterial liquid culture and Xpert MTB/RIF was performed on 2 induced sputa obtained from each participant. Children were categorised as definite-TB (culture or qPCR [Xpert MTB/RIF] confirmed), unlikely-TB (improvement of symptoms without TB treatment on follow-up) and unconfirmed-TB (all other children). RESULTS: Amongst 214 children with a median age of 36 months (interquartile range, [IQR] 19–66 months), 34 (16 %) had definite-TB, 86 (40 %) had unconfirmed-TB and 94 (44 %) were classified as unlikely-TB. Moraxella catarrhalis (64 %), Streptococcus pneumoniae (42 %), Haemophilus influenzae spp (29 %) and Staphylococcus aureus (22 %) were the most common bacteria detected in NP samples. Other bacteria detected included Mycoplasma pneumoniae (9 %), Bordetella pertussis (7 %) and Chlamydophila pneumoniae (4 %). The most common viruses detected included metapneumovirus (19 %), rhinovirus (15 %), influenza virus C (9 %), adenovirus (7 %), cytomegalovirus (7 %) and coronavirus O43 (5.6 %). Both bacteria and viruses were detected in 73, 55 and 56 % of the definite, unconfirmed and unlikely-TB groups, respectively. There were no significant differences in the distribution of respiratory microbes between children with and without TB. Using quadratic discriminant analysis, human metapneumovirus, C. pneumoniae, coronavirus 043, influenza virus C virus, rhinovirus and cytomegalovirus best discriminated children with definite-TB from the other groups of children. CONCLUSIONS: A broad range of potential respiratory pathogens was detected in children with suspected TB. There was no clear association between TB categorisation and detection of a specific pathogen. Further work is needed to explore potential pathogen interactions and their role in the pathogenesis of PTB. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1934-z) contains supplementary material, which is available to authorized users.",2016 Oct 24,"['Dube, Felix S.', 'Kaba, Mamadou', 'Robberts, F. J. Lourens', 'Tow, Lemese Ah', 'Lubbe, Sugnet', 'Zar, Heather J.', 'Nicol, Mark P.']",BMC Infect Dis,,,True
e26b6173b72a118e2b65869e3ba0cc176a3bb751,PMC,Comparison of incubation period distribution of human infections with MERS-CoV in South Korea and Saudi Arabia,http://dx.doi.org/10.1038/srep35839,PMC5075793,27775012,CC BY,"The incubation period is an important epidemiologic distribution, it is often incorporated in case definitions, used to determine appropriate quarantine periods, and is an input to mathematical modeling studies. Middle East Respiratory Syndrome coronavirus (MERS) is an emerging infectious disease in the Arabian Peninsula. There was a large outbreak of MERS in South Korea in 2015. We examined the incubation period distribution of MERS coronavirus infection for cases in South Korea and in Saudi Arabia. Using parametric and nonparametric methods, we estimated a mean incubation period of 6.9 days (95% credibility interval: 6.3–7.5) for cases in South Korea and 5.0 days (95% credibility interval: 4.0–6.6) among cases in Saudi Arabia. In a log-linear regression model, the mean incubation period was 1.42 times longer (95% credibility interval: 1.18–1.71) among cases in South Korea compared to Saudi Arabia. The variation that we identified in the incubation period distribution between locations could be associated with differences in ascertainment or reporting of exposure dates and illness onset dates, differences in the source or mode of infection, or environmental differences.",2016 Oct 24,"['Virlogeux, Victor', 'Fang, Vicky J.', 'Park, Minah', 'Wu, Joseph T.', 'Cowling, Benjamin J.']",Sci Rep,,,True
0fc01f8a6bb755f52b6407df7cb8c9accd15450e,PMC,Involvement of P2X7 receptor signaling on regulating the differentiation of Th17 cells and type II collagen-induced arthritis in mice,http://dx.doi.org/10.1038/srep35804,PMC5075966,27775097,CC BY,"Interleukin (IL)-17 producing T helper (Th17) cells are major effector cells in the pathogenesis of rheumatoid arthritis (RA). The P2X7 receptor (P2X7R) has emerged as a potential site in the regulation of inflammation in RA but little is known of its functional role on the differentiation of Th17 cells. This study investigates the in vitro and in vivo effects of P2X7R on Th17 cell differentiation during type II collagen (CII) induced experimental arthritis model. In CII-treated dendritic cells (DCs) and DC/CD4(+) T coculture system, pretreatment with pharmacological antagonists of P2X7R (Suramin and A-438079) caused strong inhibition of production of Th17-promoting cytokines (IL-1β, TGF-β1, IL-23p19 and IL-6). Exposure to CII induced the elevation of mRNAs encoding retinoic acid receptor-related orphan receptor α and γt, which were abolished by pretreatment with P2X7R antagonists. Furthermore, blocking P2X7R signaling abolished the CII-mediated increase in IL-17A. Blockade of P2X7R remarkably inhibited hind paw swelling and ameliorated pathological changes in ankle joint of the collagen-induced arthritis mice. Thus, we demonstrated a novel function for P2X7R signaling in regulating CII-induced differentiation of Th17 cells. P2X7R signaling facilitates the development of the sophisticated network of DC-derived cytokines that favors a Th17 phenotype.",2016 Oct 24,"['Fan, Zhi-Dan', 'Zhang, Ya-Yuan', 'Guo, Yi-Hong', 'Huang, Na', 'Ma, Hui-Hui', 'Huang, Hui', 'Yu, Hai-Guo']",Sci Rep,,,True
c7d87ef17e8863714b7ccd091373777918e9131d,PMC,The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: an observational study,http://dx.doi.org/10.1186/s13613-016-0203-z,PMC5078123,27778310,CC BY,"BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) has caused several hospital outbreaks, including a major outbreak at King Abdulaziz Medical City, a 940-bed tertiary-care hospital in Riyadh, Saudi Arabia (August–September 2015). To learn from our experience, we described the critical care response to the outbreak. METHODS: This observational study was conducted at the Intensive Care Department which covered 5 ICUs with 60 single-bedded rooms. We described qualitatively and, as applicable, quantitatively the response of intensive care services to the outbreak. The clinical course and outcomes of healthcare workers (HCWs) who had MERS were noted. RESULTS: Sixty-three MERS patients were admitted to 3 MERS-designated ICUs during the outbreak (peak census = 27 patients on August 25, 2015, and the last new case on September 13, 2015). Most patients had multiorgan failure. Eight HCWs had MERS requiring ICU admission (median stay = 28 days): Seven developed acute respiratory distress syndrome, four were treated with prone positioning, four needed continuous renal replacement therapy and one had extracorporeal membrane oxygenation. The hospital mortality of ICU MERS patients was 63.4 % (0 % for the HCWs). In response to the outbreak, the number of negative-pressure rooms was increased from 14 to 38 rooms in 3 MERS-designated ICUs. Patients were managed with a nurse-to-patient ratio of 1:0.8. Infection prevention practices were intensified. As a surrogate, surface disinfectant and hand hygiene gel consumption increased by ~30 % and 17 N95 masks were used per patient/day on average. Family visits were restricted to 2 h/day. Although most ICU staff expressed concerns about acquiring MERS, all reported to work normally. During the outbreak, 27.0 % of nurses and 18.4 % of physicians working in the MERS-designated ICUs reported upper respiratory symptoms, and were tested for MERS-CoV. Only 2/196 (1.0 %) ICU nurses and 1/80 (1.3 %) physician tested positive, had mild disease and recovered fully. The total sick leave duration was 138 days for nurses and 30 days for physicians. CONCLUSIONS: Our hospital outbreak of MERS resulted in 63 patients requiring organ support and prolonged ICU stay with a high mortality rate. The ICU response required careful facility and staff management and proper infection control and prevention practices.",2016 Oct 24,"['Al-Dorzi, Hasan M.', 'Aldawood, Abdulaziz S.', 'Khan, Raymond', 'Baharoon, Salim', 'Alchin, John D.', 'Matroud, Amal A.', 'Al Johany, Sameera M.', 'Balkhy, Hanan H.', 'Arabi, Yaseen M.']",Ann Intensive Care,,,True
01bf19ea2cb2baab425377eaae3286190e9bf975,PMC,Endogenous Retrovirus ev21 Dose Not Recombine with ALV-J and Induces the Expression of ISGs in the Host,http://dx.doi.org/10.3389/fcimb.2016.00140,PMC5078265,27826543,CC BY,"Avian leukosis virus subgroup J (ALV-J) infection can cause tumors and immunosuppression. Endogenous viruses integrate into host genomes and can recombine with exogenous avian leukosis virus (ALV). In this study, we analyzed the interaction of endogenous retrovirus 21 (ev21) with the ALV-J in late-feathering Chinese yellow chicken. Two ALV-J strains M180 and K243 were isolated from late-feathering and fast-feathering Chinese yellow chicken flocks, respectively. The env gene of the two strains showed 94.2–94.8% nucleotide identity with reference ALV-J strains. Compared with the env gene and the LTR of ev21 and M180, the nucleotide identity of LTR was 69.7% and env gene was 58.4%, respectively, especially the amino acid identity of env gene as low as 14.2%. Phylogenetic analysis of the nucleotide sequence of the env gene and the 3′LTR showed that M180 was closely related to ALV-J, and was located in a distinct group with ev21 in the phylogenetic tree. Using co-immunoprecipitation (co-IP), we next demonstrate that the envelope protein of ev21 does not interact with the M180 envelope protein. We further show that the envelope protein of ev21 cannot activate ALV-J LTR promoter activity using luciferase-reporter assays. qPCR and western blot analysis revealed that envelope protein of endogenous ev21 can facilitate the expression of PKR at 6h post ALV-J infection (hpi) and facilitate the expression of ISG12 and CH25H at 24 hpi. However, the expression of the env gene of M180 strain was not significantly at 6 and 24 hpi. We conclude that there is no evidence of recombination between endogenous retrovirus ev21 and ALV-J strain M180 in late-feathering Chinese yellow chicken, and envelope protein of ev21 can affect the expression of host ISGs, but appears not to influence the replication of ALV-J strain M180. This is the first report of interaction among the endogenous retrovirus ev21, ALV-J and the late-feathering chicken.",2016 Oct 25,"['Feng, Min', 'Tan, Yan', 'Dai, Manman', 'Li, Yuanfang', 'Xie, Tingting', 'Li, Hongmei', 'Shi, Meiqing', 'Zhang, Xiquan']",Front Cell Infect Microbiol,,,True
ac8d2e900ee0c6d713d153782a530ddee6d606aa,PMC,Influenza A virus PB1-F2 protein prolongs viral shedding in chickens lengthening the transmission window,http://dx.doi.org/10.1099/jgv.0.000584,PMC5078828,27558742,CC BY,"Avian influenza is a significant economic burden on the poultry industry in geographical regions where it is enzootic. It also poses a public health concern when avian influenza subtypes infect humans, often with high mortality. Understanding viral genetic factors which positively contribute to influenza A virus (IAV) fitness – infectivity, spread and pathogenesis – is of great importance both for human and livestock health. PB1-F2 is a small accessory protein encoded by IAV and in mammalian hosts has been implicated in a wide range of functions that contribute to increased pathogenesis. In the avian host, the protein has been understudied despite high-level full-length conservation in avian IAV isolates, which is in contrast to the truncations of the PB1-F2 length frequently found in mammalian host isolates. Here we report that the presence of a full-length PB1-F2 protein, from a low pathogenicity H9N2 avian influenza virus, prolongs infectious virus shedding from directly inoculated chickens, thereby enhancing transmission of the virus by lengthening the transmission window to contact birds. As well as extending transmission, the presence of a full-length PB1-F2 suppresses pathogenicity evidenced by an increased minimum lethal dose in embryonated chicken eggs and increasing survival in directly infected birds when compared to a virus lacking an ORF for PB1-F2. We propose that there is a positive pressure to maintain a full-length functional PB1-F2 protein upon infection of avian hosts as it contributes to the effective transmission of IAV in the field.",2016 Oct 13,"['James, Joe', 'Howard, Wendy', 'Iqbal, Munir', 'Nair, Venugopal K.', 'Barclay, Wendy S.', 'Shelton, Holly']",J Gen Virol,,,True
6bde48b237b5f69005bfa28740e4cbeb056ecd46,PMC,Influenza A virus PB1-F2 protein prolongs viral shedding in chickens lengthening the transmission window,http://dx.doi.org/10.1099/jgv.0.000584,PMC5078828,27558742,CC BY,"Avian influenza is a significant economic burden on the poultry industry in geographical regions where it is enzootic. It also poses a public health concern when avian influenza subtypes infect humans, often with high mortality. Understanding viral genetic factors which positively contribute to influenza A virus (IAV) fitness – infectivity, spread and pathogenesis – is of great importance both for human and livestock health. PB1-F2 is a small accessory protein encoded by IAV and in mammalian hosts has been implicated in a wide range of functions that contribute to increased pathogenesis. In the avian host, the protein has been understudied despite high-level full-length conservation in avian IAV isolates, which is in contrast to the truncations of the PB1-F2 length frequently found in mammalian host isolates. Here we report that the presence of a full-length PB1-F2 protein, from a low pathogenicity H9N2 avian influenza virus, prolongs infectious virus shedding from directly inoculated chickens, thereby enhancing transmission of the virus by lengthening the transmission window to contact birds. As well as extending transmission, the presence of a full-length PB1-F2 suppresses pathogenicity evidenced by an increased minimum lethal dose in embryonated chicken eggs and increasing survival in directly infected birds when compared to a virus lacking an ORF for PB1-F2. We propose that there is a positive pressure to maintain a full-length functional PB1-F2 protein upon infection of avian hosts as it contributes to the effective transmission of IAV in the field.",2016 Oct 13,"['James, Joe', 'Howard, Wendy', 'Iqbal, Munir', 'Nair, Venugopal K.', 'Barclay, Wendy S.', 'Shelton, Holly']",J Gen Virol,,,False
af5f5cae93582ca713bbc2abaea17d7898b63f72,PMC,Pathogenesis of Korean Sapelovirus A in piglets and chicks,http://dx.doi.org/10.1099/jgv.0.000571,PMC5078829,27487773,CC BY,"Sapelovirus A (SV-A), formerly known as porcine sapelovirus as a member of a new genus Sapelovirus, is known to cause enteritis, pneumonia, polioencephalomyelitis and reproductive disorders in pigs. We have recently identified α2,3-linked sialic acid on GD1a ganglioside as a functional SV-A receptor rich in the cells of pigs and chickens. However, the role of GD1a in viral pathogenesis remains elusive. Here, we demonstrated that a Korean SV-A strain could induce diarrhoea and intestinal pathology in piglets but not in chicks. Moreover, this Korean SV-A strain had mild extra-intestinal tropisms appearing as mild, non-suppurative myelitis, encephalitis and pneumonia in piglets, but not in chicks. By real-time reverse transcription (RT) PCR, higher viral RNA levels were detected in faecal samples than in sera or extra-intestinal organs from virus-inoculated piglets. Immunohistochemistry confirmed that high viral antigens were detected in the epithelial cells of intestines from virus-inoculated piglets but not from chicks. This Korean SV-A strain could bind the cultured cell lines originated from various species, but replication occurred only in cells of porcine origin. These data indicated that this Korean SV-A strain could replicate and induce pathology in piglets but not in chicks, suggesting that additional porcine-specific factors are required for virus entry and replication. In addition, this Korean SV-A strain is enteropathogenic, but could spread to the bloodstream from the gut and disseminate to extra-intestinal organs and tissues. These results will contribute to our understanding of SV-A pathogenesis so that efficient anti-sapelovirus drugs and vaccines could be developed in the future.",2016 Oct 13,"['Kim, Deok-Song', 'Kang, Mun-Il', 'Son, Kyu-Yeol', 'Bak, Geon-Yong', 'Park, Jun-Gyu', 'Hosmillo, Myra', 'Seo, Ja-Young', 'Kim, Ji-Yun', 'Alfajaro, Mia Madel', 'Soliman, Mahmoud', 'Baek, Yeong-Bin', 'Cho, Eun-Hyo', 'Lee, Ju-Hwan', 'Kwon, Joseph', 'Choi, Jong-Soon', 'Goodfellow, Ian', 'Cho, Kyoung-Oh']",J Gen Virol,,,True
96a89e5c0df1a32d5e2864966057fab04d2e3a23,PMC,Fast type I interferon response protects astrocytes from flavivirus infection and virus-induced cytopathic effects,http://dx.doi.org/10.1186/s12974-016-0748-7,PMC5078952,27776548,CC BY,"BACKGROUND: Neurotropic flaviviruses such as tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV), West Nile virus (WNV), and Zika virus (ZIKV) are causative agents of severe brain-related diseases including meningitis, encephalitis, and microcephaly. We have previously shown that local type I interferon response within the central nervous system (CNS) is involved in the protection of mice against tick-borne flavivirus infection. However, the cells responsible for mounting this protective response are not defined. METHODS: Primary astrocytes were isolated from wild-type (WT) and interferon alpha receptor knock out (IFNAR(−/−)) mice and infected with neurotropic flaviviruses. Viral replication and spread, IFN induction and response, and cellular viability were analyzed. Transcriptional levels in primary astrocytes treated with interferon or supernatant from virus-infected cells were analyzed by RNA sequencing and evaluated by different bioinformatics tools. RESULTS: Here, we show that astrocytes control viral replication of different TBEV strains, JEV, WNV, and ZIKV. In contrast to fibroblast, astrocytes mount a rapid interferon response and restrict viral spread. Furthermore, basal expression levels of key interferon-stimulated genes are high in astrocytes compared to mouse embryonic fibroblasts. Bioinformatic analysis of RNA-sequencing data reveals that astrocytes have established a basal antiviral state which contributes to the rapid viral recognition and upregulation of interferons. The most highly upregulated pathways in neighboring cells were linked to type I interferon response and innate immunity. The restriction in viral growth was dependent on interferon signaling, since loss of the interferon receptor, or its blockade in wild-type cells, resulted in high viral replication and virus-induced cytopathic effects. Astrocyte supernatant from TBEV-infected cells can restrict TBEV growth in astrocytes already 6 h post infection, the effect on neurons is highly reinforced, and astrocyte supernatant from 3 h post infection is already protective. CONCLUSIONS: These findings suggest that the combination of an intrinsic constitutive antiviral response and the fast induction of type I IFN production by astrocytes play an important role in self-protection of astrocytes and suppression of flavivirus replication in the CNS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-016-0748-7) contains supplementary material, which is available to authorized users.",2016 Oct 24,"['Lindqvist, Richard', 'Mundt, Filip', 'Gilthorpe, Jonathan D.', 'Wölfel, Silke', 'Gekara, Nelson O.', 'Kröger, Andrea', 'Överby, Anna K.']",J Neuroinflammation,,,True
44cbdded77107e8c97330deef77b1b761a9bb229,PMC,Differential expression of lncRNAs during the HIV replication cycle: an underestimated layer in the HIV-host interplay,http://dx.doi.org/10.1038/srep36111,PMC5080576,27782208,CC BY,"Studying the effects of HIV infection on the host transcriptome has typically focused on protein-coding genes. However, recent advances in the field of RNA sequencing revealed that long non-coding RNAs (lncRNAs) add an extensive additional layer to the cell’s molecular network. Here, we performed transcriptome profiling throughout a primary HIV infection in vitro to investigate lncRNA expression at the different HIV replication cycle processes (reverse transcription, integration and particle production). Subsequently, guilt-by-association, transcription factor and co-expression analysis were performed to infer biological roles for the lncRNAs identified in the HIV-host interplay. Many lncRNAs were suggested to play a role in mechanisms relying on proteasomal and ubiquitination pathways, apoptosis, DNA damage responses and cell cycle regulation. Through transcription factor binding analysis, we found that lncRNAs display a distinct transcriptional regulation profile as compared to protein coding mRNAs, suggesting that mRNAs and lncRNAs are independently modulated. In addition, we identified five differentially expressed lncRNA-mRNA pairs with mRNA involvement in HIV pathogenesis with possible cis regulatory lncRNAs that control nearby mRNA expression and function. Altogether, the present study demonstrates that lncRNAs add a new dimension to the HIV-host interplay and should be further investigated as they may represent targets for controlling HIV replication.",2016 Oct 26,"['Trypsteen, Wim', 'Mohammadi, Pejman', 'Van Hecke, Clarissa', 'Mestdagh, Pieter', 'Lefever, Steve', 'Saeys, Yvan', 'De Bleser, Pieter', 'Vandesompele, Jo', 'Ciuffi, Angela', 'Vandekerckhove, Linos', 'De Spiegelaere, Ward']",Sci Rep,,,True
9f13bcae6ae451b9a0c4d2f22c6557fcfbc2c3f7,PMC,Differential expression of lncRNAs during the HIV replication cycle: an underestimated layer in the HIV-host interplay,http://dx.doi.org/10.1038/srep36111,PMC5080576,27782208,CC BY,"Studying the effects of HIV infection on the host transcriptome has typically focused on protein-coding genes. However, recent advances in the field of RNA sequencing revealed that long non-coding RNAs (lncRNAs) add an extensive additional layer to the cell’s molecular network. Here, we performed transcriptome profiling throughout a primary HIV infection in vitro to investigate lncRNA expression at the different HIV replication cycle processes (reverse transcription, integration and particle production). Subsequently, guilt-by-association, transcription factor and co-expression analysis were performed to infer biological roles for the lncRNAs identified in the HIV-host interplay. Many lncRNAs were suggested to play a role in mechanisms relying on proteasomal and ubiquitination pathways, apoptosis, DNA damage responses and cell cycle regulation. Through transcription factor binding analysis, we found that lncRNAs display a distinct transcriptional regulation profile as compared to protein coding mRNAs, suggesting that mRNAs and lncRNAs are independently modulated. In addition, we identified five differentially expressed lncRNA-mRNA pairs with mRNA involvement in HIV pathogenesis with possible cis regulatory lncRNAs that control nearby mRNA expression and function. Altogether, the present study demonstrates that lncRNAs add a new dimension to the HIV-host interplay and should be further investigated as they may represent targets for controlling HIV replication.",2016 Oct 26,"['Trypsteen, Wim', 'Mohammadi, Pejman', 'Van Hecke, Clarissa', 'Mestdagh, Pieter', 'Lefever, Steve', 'Saeys, Yvan', 'De Bleser, Pieter', 'Vandesompele, Jo', 'Ciuffi, Angela', 'Vandekerckhove, Linos', 'De Spiegelaere, Ward']",Sci Rep,,,True
d259c80b55cb69486ef75e66d13fe60688a1e028,PMC,Middle East Respiratory Coronavirus Accessory Protein 4a Inhibits PKR-Mediated Antiviral Stress Responses,http://dx.doi.org/10.1371/journal.ppat.1005982,PMC5081173,27783669,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infections that can be life-threatening. To establish an infection and spread, MERS-CoV, like most other viruses, must navigate through an intricate network of antiviral host responses. Besides the well-known type I interferon (IFN-α/β) response, the protein kinase R (PKR)-mediated stress response is being recognized as an important innate response pathway. Upon detecting viral dsRNA, PKR phosphorylates eIF2α, leading to the inhibition of cellular and viral translation and the formation of stress granules (SGs), which are increasingly recognized as platforms for antiviral signaling pathways. It is unknown whether cellular infection by MERS-CoV activates the stress response pathway or whether the virus has evolved strategies to suppress this infection-limiting pathway. Here, we show that cellular infection with MERS-CoV does not lead to the formation of SGs. By transiently expressing the MERS-CoV accessory proteins individually, we identified a role of protein 4a (p4a) in preventing activation of the stress response pathway. Expression of MERS-CoV p4a impeded dsRNA-mediated PKR activation, thereby rescuing translation inhibition and preventing SG formation. In contrast, p4a failed to suppress stress response pathway activation that is independent of PKR and dsRNA. MERS-CoV p4a is a dsRNA binding protein. Mutation of the dsRNA binding motif in p4a disrupted its PKR antagonistic activity. By inserting p4a in a picornavirus lacking its natural PKR antagonist, we showed that p4a exerts PKR antagonistic activity also under infection conditions. However, a recombinant MERS-CoV deficient in p4a expression still suppressed SG formation, indicating the expression of at least one other stress response antagonist. This virus also suppressed the dsRNA-independent stress response pathway. Thus, MERS-CoV interferes with antiviral stress responses using at least two different mechanisms, with p4a suppressing the PKR-dependent stress response pathway, probably by sequestering dsRNA. MERS-CoV p4a represents the first coronavirus stress response antagonist described.",2016 Oct 26,"['Rabouw, Huib H.', 'Langereis, Martijn A.', 'Knaap, Robert C. M.', 'Dalebout, Tim J.', 'Canton, Javier', 'Sola, Isabel', 'Enjuanes, Luis', 'Bredenbeek, Peter J.', 'Kikkert, Marjolein', 'de Groot, Raoul J.', 'van Kuppeveld, Frank J. M.']",PLoS Pathog,,,True
ec99df59b1b63a5da4b31c203e8e1eab566fba68,PMC,Mechanism of Fibronectin Binding to Human Trabecular Meshwork Exosomes and Its Modulation by Dexamethasone,http://dx.doi.org/10.1371/journal.pone.0165326,PMC5081181,27783649,CC BY,"Exosomes are emerging as important mediators of cell-matrix interactions by means of specific adhesion proteins. Changes in the tissue-specific exosomal protein expression may underlie pathological conditions whereby extracellular matrix turnover and homeostasis is disrupted. Ocular hypertension due to extracellular matrix accumulation in the trabecular meshwork is a hallmark of glucocorticoid-induced glaucoma. In the trabecular meshwork, exosomal fibronectin mediates cell matrix interactions at cellular structures called “invadosomes”. Trabecular meshwork cells use invadosomes to turn over their surrounding matrix and maintain passageways for flow of aqueous humor. In this study, we observed that human trabecular meshwork explants treated with dexamethasone released exosomes with significantly reduced amounts of fibronectin bound per exosome. Further, we found that exosome-fibronectin binding is heparan sulfate-dependent, consistent with our observation that trabecular meshwork exosomes are enriched in the heparin/heparan sulfate binding annexins A2 and A6. In this way, dexamethasone-treated explants released exosomes with a significant reduction in annexin A2 and A6 per exosome. Interestingly, we did not detect exosomal matrix metalloproteinases, but we identified abundant dipeptidyl peptidase 4, a serine protease whose activity was reduced on exosomes isolated from dexamethasone-treated explants. Together, our findings demonstrate mechanistically how corticosteroid-induced alterations in exosomal adhesion cargo and properties can account for the pathological matrix accumulation seen in many glaucoma patients.",2016 Oct 26,"['Dismuke, W. Michael', 'Klingeborn, Mikael', 'Stamer, W. Daniel']",PLoS One,,,True
45510604115249ca0df4da68553498f079b7911f,PMC,Building Viral Replication Organelles: Close Encounters of the Membrane Types,http://dx.doi.org/10.1371/journal.ppat.1005912,PMC5082816,27788266,CC BY,,2016 Oct 27,"['Nagy, Peter D.', 'Strating, Jeroen R. P. M.', 'van Kuppeveld, Frank J. M.']",PLoS Pathog,,,True
eddeda2da89b486d01f0afaf67af974b9f214306,PMC,A Generic Quantitative Risk Assessment Framework for the Entry of Bat-Borne Zoonotic Viruses into the European Union,http://dx.doi.org/10.1371/journal.pone.0165383,PMC5082878,27788234,CC BY,"Bat-borne viruses have been linked to a number of zoonotic diseases; in 2014 there have been human cases of Nipah virus (NiV) in Bangladesh and Ebola virus in West and Central Africa. Here we describe a model designed to provide initial quantitative predictions of the risk of entry of such viruses to European Union (EU) Member States (MSs) through four routes: human travel, legal trade (e.g. fruit and animal products), live animal movements and illegal importation of bushmeat. The model utilises available datasets to assess the movement via these routes between individual countries of the world and EU MSs. These data are combined with virus specific data to assess the relative risk of entry between EU MSs. As a case study, the model was parameterised for NiV. Scenario analyses showed that the selection of exporting countries with NiV and potentially contaminated trade products were essential to the accuracy of all model outputs. Uncertainty analyses of other model parameters identified that the model expected number of years to an introduction event within the EU was highly susceptible to the prevalence of NiV in bats. The relative rankings of the MSs and routes, however, were more robust. The UK, the Netherlands and Germany were consistently the most likely points of entry and the ranking of most MSs varied by no more than three places (maximum variation five places). Legal trade was consistently the most likely route of entry, only falling below human travel when the estimate of the prevalence of NiV in bats was particularly low. Any model-based calculation is dependent on the data available to feed into the model and there are distinct gaps in our knowledge, particularly in regard to various pathogen/virus as well as host/bat characteristics. However, the strengths of this model lie in the provision of relative comparisons of risk among routes and MSs. The potential for expansion of the model to include other routes and viruses and the possibility of rapid parameterisation demonstrates its potential for use in an outbreak situation.",2016 Oct 27,"['Simons, Robin R. L.', 'Horigan, Verity', 'Gale, Paul', 'Kosmider, Rowena D.', 'Breed, Andrew C.', 'Snary, Emma L.']",PLoS One,,,True
a382a62bbd387279327333abd96be2aa76445ace,PMC,Microorganisms Causing Community-Acquired Acute Bronchitis: The Role of Bacterial Infection,http://dx.doi.org/10.1371/journal.pone.0165553,PMC5082923,27788254,CC BY,"BACKGROUND: Although acute bronchitis is quite common, there is relatively limited information regarding the microorganisms that are involved in this illness. METHODS: We performed a prospective study of acute bronchitis at 31 hospitals and clinics in Korea from July 2011 to June 2012. Sputum specimens were collected for polymerase chain reaction (PCR) and culture of microorganisms. RESULTS: Of the 811 enrolled patients, 291 had acceptable sputum specimens that were included for analysis of the etiologic distribution. With multiplex PCR testing, viruses were identified in 36.1% (105/291), most commonly rhinovirus (25.8%) and coronavirus (3.8%). Typical bacteria were isolated in 126/291 (43.3%) patients. Among these patients Haemophilus influenzae (n = 39) and Streptococcus pneumoniae (n = 30) were isolated most commonly; atypical bacteria were identified in 44 (15.1%) patients. Bacteria-only, virus-only, and mixed infections (bacteria plus virus) accounted for 36.7% (98/291), 17.2% (50/291), and 18.9% (55/291) of infections, respectively. In particular, 52.4% of patients with viral infection had a concurrent bacterial infection, and rhinovirus was the most common virus in mixed infections (40/55). Additionally, infections with typical bacteria were more common in patients with chronic lung disease (p = 0.029), and typical bacterial infections showed a trend towards a higher prevalence with older age (p = 0.001). CONCLUSIONS: Bacteria were associated with almost half of community-acquired acute bronchitis cases. Additional studies are required to further illuminate the role of bacteria and to identify patient groups most likely to benefit from antibiotic treatment.",2016 Oct 27,"['Park, Ji Young', 'Park, Sunghoon', 'Lee, Sun Hwa', 'Lee, Myung Goo', 'Park, Yong Bum', 'Oh, Kil Chan', 'Lee, Jae-Myung', 'Kim, Do Il', 'Seo, Ki-Hyun', 'Shin, Kyeong-Cheol', 'Yoo, Kwang Ha', 'Ko, Yongchun', 'Jang, Seung Hun', 'Jung, Ki-Suck', 'Hwang, Yong Il']",PLoS One,,,True
0892e16c218542d3a099d7b10aec24cab4bfce55,PMC,Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model,http://dx.doi.org/10.18632/oncotarget.9114,PMC5085160,27145284,CC BY,"Advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) have led to improved progression-free survival of many patients; however the therapies are toxic, rarely achieve durable long-term complete responses and are not curative. Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site. The local antibody delivery led to marked immune checkpoint blockade. Tumor growth diminished 5 times and tumor weight reduced 50–80% when compared with the anti-CAIX CAR T cells alone in a humanized mice model of ccRCC. The expression of PD-L1 and Ki67 in the tumors decreased and an increase in granzyme B levels was found in CAR T cells. The anti-PD-L1 IgG1 isotype, which is capable of mediating ADCC, was also able to recruit human NK cells to the tumor site in vivo. These armed second-generation CAR T cells empowered to secrete human anti-PD-L1 antibodies in the ccRCC milieu to combat T cell exhaustion is an innovation in this field that should provide renewed potential for CAR T cell immunotherapy of solid tumors where limited efficacy is currently seen.",2016 Apr 29,"['Suarez, Eloah Rabello', 'Chang, De-Kuan', 'Sun, Jiusong', 'Sui, Jianhua', 'Freeman, Gordon J.', 'Signoretti, Sabina', 'Zhu, Quan', 'Marasco, Wayne A.']",Oncotarget,,,True
74eccf041d34a1cebad39e386cba617d1bd996ea,PMC,Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model,http://dx.doi.org/10.18632/oncotarget.9114,PMC5085160,27145284,CC BY,"Advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) have led to improved progression-free survival of many patients; however the therapies are toxic, rarely achieve durable long-term complete responses and are not curative. Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site. The local antibody delivery led to marked immune checkpoint blockade. Tumor growth diminished 5 times and tumor weight reduced 50–80% when compared with the anti-CAIX CAR T cells alone in a humanized mice model of ccRCC. The expression of PD-L1 and Ki67 in the tumors decreased and an increase in granzyme B levels was found in CAR T cells. The anti-PD-L1 IgG1 isotype, which is capable of mediating ADCC, was also able to recruit human NK cells to the tumor site in vivo. These armed second-generation CAR T cells empowered to secrete human anti-PD-L1 antibodies in the ccRCC milieu to combat T cell exhaustion is an innovation in this field that should provide renewed potential for CAR T cell immunotherapy of solid tumors where limited efficacy is currently seen.",2016 Apr 29,"['Suarez, Eloah Rabello', 'Chang, De-Kuan', 'Sun, Jiusong', 'Sui, Jianhua', 'Freeman, Gordon J.', 'Signoretti, Sabina', 'Zhu, Quan', 'Marasco, Wayne A.']",Oncotarget,,,False
0660d9281c1607ca1ca9cb62dfa00b56f49ddee1,PMC,The Last Ten Years of Advancements in Plant-Derived Recombinant Vaccines against Hepatitis B,http://dx.doi.org/10.3390/ijms17101715,PMC5085746,27754367,CC BY,"Disease prevention through vaccination is considered to be the greatest contribution to public health over the past century. Every year more than 100 million children are vaccinated with the standard World Health Organization (WHO)-recommended vaccines including hepatitis B (HepB). HepB is the most serious type of liver infection caused by the hepatitis B virus (HBV), however, it can be prevented by currently available recombinant vaccine, which has an excellent record of safety and effectiveness. To date, recombinant vaccines are produced in many systems of bacteria, yeast, insect, and mammalian and plant cells. Among these platforms, the use of plant cells has received considerable attention in terms of intrinsic safety, scalability, and appropriate modification of target proteins. Research groups worldwide have attempted to develop more efficacious plant-derived vaccines for over 30 diseases, most frequently HepB and influenza. More inspiring, approximately 12 plant-made antigens have already been tested in clinical trials, with successful outcomes. In this study, the latest information from the last 10 years on plant-derived antigens, especially hepatitis B surface antigen, approaches are reviewed and breakthroughs regarding the weak points are also discussed.",2016 Oct 13,"['Joung, Young Hee', 'Park, Se Hee', 'Moon, Ki-Beom', 'Jeon, Jae-Heung', 'Cho, Hye-Sun', 'Kim, Hyun-Soon']",Int J Mol Sci,,,True
1db51d8c217cae965ebad4dabf0651a2ecd62e53,PMC,Viral Metagenomics on Blood-Feeding Arthropods as a Tool for Human Disease Surveillance,http://dx.doi.org/10.3390/ijms17101743,PMC5085771,27775568,CC BY,"Surveillance and monitoring of viral pathogens circulating in humans and wildlife, together with the identification of emerging infectious diseases (EIDs), are critical for the prediction of future disease outbreaks and epidemics at an early stage. It is advisable to sample a broad range of vertebrates and invertebrates at different temporospatial levels on a regular basis to detect possible candidate viruses at their natural source. However, virus surveillance systems can be expensive, costly in terms of finances and resources and inadequate for sampling sufficient numbers of different host species over space and time. Recent publications have presented the concept of a new virus surveillance system, coining the terms “flying biological syringes”, “xenosurveillance” and “vector-enabled metagenomics”. According to these novel and promising surveillance approaches, viral metagenomics on engorged mosquitoes might reflect the viral diversity of numerous mammals, birds and humans, combined in the mosquitoes’ blood meal during feeding on the host. In this review article, we summarize the literature on vector-enabled metagenomics (VEM) techniques and its application in disease surveillance in humans. Furthermore, we highlight the combination of VEM and “invertebrate-derived DNA” (iDNA) analysis to identify the host DNA within the mosquito midgut.",2016 Oct 19,"['Brinkmann, Annika', 'Nitsche, Andreas', 'Kohl, Claudia']",Int J Mol Sci,,,True
fba08f3ce8a1335d06623126e44863cf1e73a509,PMC,Mutagenic Effects of Ribavirin on Hepatitis E Virus—Viral Extinction versus Selection of Fitness-Enhancing Mutations,http://dx.doi.org/10.3390/v8100283,PMC5086615,27754363,CC BY,"Hepatitis E virus (HEV), an important agent of viral hepatitis worldwide, can cause severe courses of infection in pregnant women and immunosuppressed patients. To date, HEV infections can only be treated with ribavirin (RBV). Major drawbacks of this therapy are that RBV is not approved for administration to pregnant women and that the virus can acquire mutations, which render the intra-host population less sensitive or even resistant to RBV. One of the proposed modes of action of RBV is a direct mutagenic effect on viral genomes, inducing mismatches and subsequent nucleotide substitutions. These transition events can drive the already error-prone viral replication beyond an error threshold, causing viral population extinction. In contrast, the expanded heterogeneous viral population can facilitate selection of mutant viruses with enhanced replication fitness. Emergence of these mutant viruses can lead to therapeutic failure. Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis.",2016 Oct 13,"['Todt, Daniel', 'Walter, Stephanie', 'Brown, Richard J. P.', 'Steinmann, Eike']",Viruses,,,True
39683dd78bcf6b301cbed610b6e3213a5ce33380,PMC,Griffithsin: An Antiviral Lectin with Outstanding Therapeutic Potential,http://dx.doi.org/10.3390/v8100296,PMC5086628,27783038,CC BY,"Griffithsin (GRFT), an algae-derived lectin, is one of the most potent viral entry inhibitors discovered to date. It is currently being developed as a microbicide with broad-spectrum activity against several enveloped viruses. GRFT can inhibit human immunodeficiency virus (HIV) infection at picomolar concentrations, surpassing the ability of most anti-HIV agents. The potential to inhibit other viruses as well as parasites has also been demonstrated. Griffithsin’s antiviral activity stems from its ability to bind terminal mannoses present in high-mannose oligosaccharides and crosslink these glycans on the surface of the viral envelope glycoproteins. Here, we review structural and biochemical studies that established mode of action and facilitated construction of GRFT analogs, mechanisms that may lead to resistance, and in vitro and pre-clinical results that support the therapeutic potential of this lectin.",2016 Oct 24,"['Lusvarghi, Sabrina', 'Bewley, Carole A.']",Viruses,,,True
9db44eda8b352d1e7e5f73d7b5587659aa256151,PMC,The Influenza Virus Protein PB1-F2 Increases Viral Pathogenesis through Neutrophil Recruitment and NK Cells Inhibition,http://dx.doi.org/10.1371/journal.pone.0165361,PMC5087861,27798704,CC BY,"The influenza A virus (IAV) PB1-F2 protein is a virulence factor contributing to the pathogenesis observed during IAV infections in mammals. In this study, using a mouse model, we compared the host response associated with PB1-F2 with an early transcriptomic signature that was previously associated with neutrophils and consecutively fatal IAV infections. This allowed us to show that PB1-F2 is partly involved in neutrophil-related mechanisms leading to death. Using neutropenic mice, we confirmed that the harmful effect of PB1-F2 is due to an excessive inflammation mediated by an increased neutrophil mobilization. We identified the downstream effects of this PB1-F2-exacerbated neutrophil recruitment. PB1-F2 had no impact on the lymphocyte recruitment in the airways at day 8 pi. However, functional genomics analysis and flow cytometry in broncho-alveolar lavages at 4 days pi revealed that PB1-F2 induced a NK cells deficiency. Thus, our results identify PB1-F2 as an important immune disruptive factor during the IAV infection.",2016 Oct 31,"['Vidy, Aurore', 'Maisonnasse, Pauline', 'Da Costa, Bruno', 'Delmas, Bernard', 'Chevalier, Christophe', 'Le Goffic, Ronan']",PLoS One,,,True
028949943b9f67a541a4d59504d87b9ddbe7713b,PMC,The Influenza Virus Protein PB1-F2 Increases Viral Pathogenesis through Neutrophil Recruitment and NK Cells Inhibition,http://dx.doi.org/10.1371/journal.pone.0165361,PMC5087861,27798704,CC BY,"The influenza A virus (IAV) PB1-F2 protein is a virulence factor contributing to the pathogenesis observed during IAV infections in mammals. In this study, using a mouse model, we compared the host response associated with PB1-F2 with an early transcriptomic signature that was previously associated with neutrophils and consecutively fatal IAV infections. This allowed us to show that PB1-F2 is partly involved in neutrophil-related mechanisms leading to death. Using neutropenic mice, we confirmed that the harmful effect of PB1-F2 is due to an excessive inflammation mediated by an increased neutrophil mobilization. We identified the downstream effects of this PB1-F2-exacerbated neutrophil recruitment. PB1-F2 had no impact on the lymphocyte recruitment in the airways at day 8 pi. However, functional genomics analysis and flow cytometry in broncho-alveolar lavages at 4 days pi revealed that PB1-F2 induced a NK cells deficiency. Thus, our results identify PB1-F2 as an important immune disruptive factor during the IAV infection.",2016 Oct 31,"['Vidy, Aurore', 'Maisonnasse, Pauline', 'Da Costa, Bruno', 'Delmas, Bernard', 'Chevalier, Christophe', 'Le Goffic, Ronan']",PLoS One,,,False
8745be1dc78adeffdc2f243e3597390ddd07b456,PMC,A retrospective study detects a novel variant of porcine epidemic diarrhea virus in England in archived material from the year 2000,http://dx.doi.org/10.7717/peerj.2564,PMC5088618,27812401,CC BY,"Outbreaks of porcine epidemic diarrhea (PED) were first recorded in England in the 1970s and continued to be confirmed until 2002. Retrospective analysis of archived material from one of the last confirmed cases in England in the year 2000 demonstrates the previous existence of a very diverse PED virus strain. Following the outbreaks of PED in North America in 2013, there has been renewed interest in phylogenetic analysis of sequences from PEDV strains worldwide. There is a gap in the available sequence data between the mid 1980s and the mid 2000s. This work is an example of how this gap can be at least partially filled by the examination of archived material.",2016 Oct 27,"['Steinbach, Falko', 'Dastjerdi, Akbar', 'Peake, Julie', 'La Rocca, S. Anna', 'Tobin, Frank P.', 'Frossard, Jean-Pierre', 'Williamson, Susanna']",PeerJ,,,True
711a2350fec569de818a1bd51ab4a3a8b793918c,PMC,"Key Ethical Issues Discussed at CDC-Sponsored International, Regional Meetings to Explore Cultural Perspectives and Contexts on Pandemic Influenza Preparedness and Response",http://dx.doi.org/10.15171/ijhpm.2016.55,PMC5088725,27801360,CC BY,"Background: Recognizing the importance of having a broad exploration of how cultural perspectives may shape thinking about ethical considerations, the Centers for Disease Control and Prevention (CDC) funded four regional meetings in Africa, Asia, Latin America, and the Eastern Mediterranean to explore these perspectives relevant to pandemic influenza preparedness and response. The meetings were attended by 168 health professionals, scientists, academics, ethicists, religious leaders, and other community members representing 40 countries in these regions. Methods: We reviewed the meeting reports, notes and stories and mapped outcomes to the key ethical challenges for pandemic influenza response described in the World Health Organization’s (WHO’s) guidance, Ethical Considerations in Developing a Public Health Response to Pandemic Influenza: transparency and public engagement, allocation of resources, social distancing, obligations to and of healthcare workers, and international collaboration. Results: The important role of transparency and public engagement were widely accepted among participants. However, there was general agreement that no ""one size fits all"" approach to allocating resources can address the variety of economic, cultural and other contextual factors that must be taken into account. The importance of social distancing as a tool to limit disease transmission was also recognized, but the difficulties associated with this measure were acknowledged. There was agreement that healthcare workers often have competing obligations and that government has a responsibility to assist healthcare workers in doing their job by providing appropriate training and equipment. Finally, there was agreement about the importance of international collaboration for combating global health threats. Conclusion: Although some cultural differences in the values that frame pandemic preparedness and response efforts were observed, participants generally agreed on the key ethical principles discussed in the WHO’s guidance. Most significantly the input gathered from these regional meetings pointed to the important role that procedural ethics can play in bringing people and countries together to respond to the shared health threat posed by a pandemic influenza despite the existence of cultural differences.",2016 May 17,"['Lor, Aun', 'Thomas, James C.', 'Barrett, Drue H.', 'Ortmann, Leonard W.', 'Herrera Guibert, Dionisio J.']",Int J Health Policy Manag,,,True
a3f9d6933e737f7f0a7bd27a54a9bb4882eca041,PMC,Clinical and Epidemiologic Characteristics of Hospitalized Patients with Laboratory-Confirmed Respiratory Syncytial Virus Infection in Eastern China between 2009 and 2013: A Retrospective Study,http://dx.doi.org/10.1371/journal.pone.0165437,PMC5089734,27802292,CC BY,"Respiratory syncytial virus (RSV) is a leading cause of morbidity and mortality worldwide in children aged <5 years and older adults with acute lower respiratory infections (ALRIs). However, few studies regarding the epidemiology of hospitalizations for RSV infection have been performed previously in China. Here, we aimed to describe the clinical and epidemiologic characteristics of hospitalized patients with laboratory-confirmed RSV infection in eastern China. Active surveillance for hospitalized ALRI patients using a broad case definition based on symptoms was performed from 2009–2013 in 12 sentinel hospitals in eastern China. Clinical and epidemiologic data pertaining to hospitalized patients of all ages with laboratory-confirmed RSV infection by PCR assay were collected and analyzed in this study. From 2009 to 2013, 1046 hospitalized patients with laboratory-confirmed RSV infection were enrolled in this study, and 14.7% of patients had subtype A, 24.2% of patients had subtype B, 23.8% of patients with subtype not performed, and 37.3% of patients had RSV coinfections with other viruses. RSV and influenza coinfections (33.3%) were the most common coinfections noted in this study. Moreover, young children aged <5 years (89.1%, 932/1046), particularly young infants aged <1 year (43.3%, 453/1046), represented the highest proportion of patients with RSV infections. In contrast, older adults aged ≥60 years (1.1%, 12/1046) represented the lowest proportion of patients with RSV infections among enrolled patients. The peak RSV infection period occurred mainly during autumn and winter, and 57% and 66% of patients exhibited symptoms such as fever (body temperature ≥38°C) and cough separately. Additionally, only a small number of patients were treated with broad-spectrum antiviral drugs, and most of patients were treated with antimicrobial drugs that were not appropriate for RSV infection. RSV is a leading viral pathogen and a common cause of viral infection in young children aged <5 years with ALRIs in eastern China. Effective vaccines and antiviral agents targeting RSV are needed to mitigate its large public health impact.",2016 Nov 1,"['Cui, Dawei', 'Feng, Luzhao', 'Chen, Yu', 'Lai, Shengjie', 'Zhang, Zike', 'Yu, Fei', 'Zheng, Shufa', 'Li, Zhongjie', 'Yu, Hongjie']",PLoS One,,,True
9586f483c1144f2e1b3105d587b826f467d02832,PMC,Autographa californica Multiple Nucleopolyhedrovirus Ac34 Protein Retains Cellular Actin-Related Protein 2/3 Complex in the Nucleus by Subversion of CRM1-Dependent Nuclear Export,http://dx.doi.org/10.1371/journal.ppat.1005994,PMC5089780,27802336,CC BY,"Actin, nucleation-promoting factors (NPFs), and the actin-related protein 2/3 complex (Arp2/3) are key elements of the cellular actin polymerization machinery. With nuclear actin polymerization implicated in ever-expanding biological processes and the discovery of the nuclear import mechanisms of actin and NPFs, determining Arp2/3 nucleo-cytoplasmic shuttling mechanism is important for understanding the function of nuclear actin. A unique feature of alphabaculovirus infection of insect cells is the robust nuclear accumulation of Arp2/3, which induces actin polymerization in the nucleus to assist in virus replication. We found that Ac34, a viral late gene product encoded by the alphabaculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV), is involved in Arp2/3 nuclear accumulation during virus infection. Further assays revealed that the subcellular distribution of Arp2/3 under steady-state conditions is controlled by chromosomal maintenance 1 (CRM1)-dependent nuclear export. Upon AcMNPV infection, Ac34 inhibits CRM1 pathway and leads to Arp2/3 retention in the nucleus.",2016 Nov 1,"['Mu, Jingfang', 'Zhang, Yongli', 'Hu, Yangyang', 'Hu, Xue', 'Zhou, Yuan', 'Zhao, He', 'Pei, Rongjuan', 'Wu, Chunchen', 'Chen, Jizheng', 'Zhao, Han', 'Yang, Kai', 'van Oers, Monique M.', 'Chen, Xinwen', 'Wang, Yun']",PLoS Pathog,,,True
126b264339dd9d8ee65cc747822e16c83af57e12,PMC,Sustaining Interferon Induction by a High-Passage Atypical Porcine Reproductive and Respiratory Syndrome Virus Strain,http://dx.doi.org/10.1038/srep36312,PMC5090871,27805024,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) strain A2MC2 induces type I interferons in cultured cells. The objective of this study was to attenuate this strain by serial passaging in MARC-145 cells and assess its virulence and immunogenicity in pigs. The A2MC2 serially passaged 90 times (A2MC2-P90) retains the feature of interferon induction. The A2MC2-P90 replicates faster with a higher virus yield than wild type A2MC2 virus. Infection of primary pulmonary alveolar macrophages (PAMs) also induces interferons. Sequence analysis showed that the A2MC2-P90 has genomic nucleic acid identity of 99.8% to the wild type but has a deletion of 543 nucleotides in nsp2. The deletion occurred in passage 60. The A2MC2-P90 genome has a total of 35 nucleotide variations from the wild type, leading to 26 amino acid differences. Inoculation of three-week-old piglets showed that A2MC2-P90 is avirulent and elicits immune response. Compared with Ingelvac PRRS(®) MLV strain, A2MC2-P90 elicits higher virus neutralizing antibodies. The attenuated IFN-inducing A2MC2-P90 should be useful for development of an improved PRRSV vaccine.",2016 Nov 2,"['Ma, Zexu', 'Yu, Ying', 'Xiao, Yueqiang', 'Opriessnig, Tanja', 'Wang, Rong', 'Yang, Liping', 'Nan, Yuchen', 'Samal, Siba K.', 'Halbur, Patrick G.', 'Zhang, Yan-Jin']",Sci Rep,,,True
67ad221f50d67a02b89b0ea67da2a74d6d463d16,PMC,Directional and reoccurring sequence change in zoonotic RNA virus genomes visualized by time-series word count,http://dx.doi.org/10.1038/srep36197,PMC5093548,27808119,CC BY,"Ebolavirus, MERS coronavirus and influenza virus are zoonotic RNA viruses, which mutate very rapidly. Viral growth depends on many host factors, but human cells may not provide the ideal growth conditions for viruses invading from nonhuman hosts. The present time-series analyses of short and long oligonucleotide compositions in these genomes showed directional changes in their composition after invasion from a nonhuman host, which are thought to recur after future invasions. In the recent West Africa Ebola outbreak, directional time-series changes in a wide range of oligonucleotides were observed in common for three geographic areas, and the directional changes were observed also for the recent MERS coronavirus epidemics starting in the Middle East. In addition, common directional changes in human influenza A viruses were observed for three subtypes, whose epidemics started independently. Long oligonucleotides that showed an evident directional change observed in common for the three subtypes corresponded to some of influenza A siRNAs, whose activities have been experimentally proven. Predicting directional and reoccurring changes in oligonucleotide composition should become important for designing diagnostic RT-PCR primers and therapeutic oligonucleotides with long effectiveness.",2016 Nov 3,"['Wada, Yoshiko', 'Wada, Kennosuke', 'Iwasaki, Yuki', 'Kanaya, Shigehiko', 'Ikemura, Toshimichi']",Sci Rep,,,True
e07f0ed517b0561a441652c8f5deaad4e80aafc5,PMC,Directional and reoccurring sequence change in zoonotic RNA virus genomes visualized by time-series word count,http://dx.doi.org/10.1038/srep36197,PMC5093548,27808119,CC BY,"Ebolavirus, MERS coronavirus and influenza virus are zoonotic RNA viruses, which mutate very rapidly. Viral growth depends on many host factors, but human cells may not provide the ideal growth conditions for viruses invading from nonhuman hosts. The present time-series analyses of short and long oligonucleotide compositions in these genomes showed directional changes in their composition after invasion from a nonhuman host, which are thought to recur after future invasions. In the recent West Africa Ebola outbreak, directional time-series changes in a wide range of oligonucleotides were observed in common for three geographic areas, and the directional changes were observed also for the recent MERS coronavirus epidemics starting in the Middle East. In addition, common directional changes in human influenza A viruses were observed for three subtypes, whose epidemics started independently. Long oligonucleotides that showed an evident directional change observed in common for the three subtypes corresponded to some of influenza A siRNAs, whose activities have been experimentally proven. Predicting directional and reoccurring changes in oligonucleotide composition should become important for designing diagnostic RT-PCR primers and therapeutic oligonucleotides with long effectiveness.",2016 Nov 3,"['Wada, Yoshiko', 'Wada, Kennosuke', 'Iwasaki, Yuki', 'Kanaya, Shigehiko', 'Ikemura, Toshimichi']",Sci Rep,,,False
033e16498132db048e7fbf0a64d99694bd302a7b,PMC,"Clinical presentations and outcomes of patients with Ebola virus disease in Freetown, Sierra Leone",http://dx.doi.org/10.1186/s40249-016-0195-9,PMC5094140,27806732,CC BY,"BACKGROUND: Clinical and laboratory data were collected and analysed from patients with Ebola virus disease (EVD) in Jui Government Hospital in Freetown, Sierra Leone, where patients with EVD were received and/or treated from October 1, 2014 to March 21, 2015 during the West Africa EVD outbreak. METHODS: The study admitted 285 patients with confirmed EVD and followed them up till the endpoint (recovery or death). EVD was confirmed by quantitative RT-PCR assays detecting blood Ebola virus (EBOV). RESULTS: Among the 285 lab-confirmed EVD cases in Jui Government Hospital, 146 recovered and 139 died, with an overall survival rate of 51.23 %. Patients under the age of 6 years had a lower survival rate (37.50 %). Most non-survivors (79.86 %) died within 7 days after admission and the mean hospitalization time for non-survivors was 5.56 ± 6.11 days. More than half survivors (63.69 %) turned blood EBOV negative within 3 weeks after admission and the mean hospitalization time for survivors was 20.38 ± 7.58 days. High blood viral load (≥10(6) copies/ml) was found to be predictive of the non-survival outcome as indicated by the Receiver Operating Characteristic (ROC) curve analysis. The probability of patients’ survival was less than 15 % when blood viral load was greater than 10(6) copies/ml. Multivariate analyses showed that blood viral load (P = 0.005), confusion (P = 0.010), abdominal pain (P = 0.003), conjunctivitis (P = 0.035), and vomiting (P = 0.004) were factors independently associated with the outcomes of EVD patients. CONCLUSIONS: Most death occurred within 1 week after admission, and patients at the age of 6 or younger had a lower survival rate. Most surviving patients turned blood EBOV negative within 1–4 weeks after admission. Factors such as high blood viral load, confusion, abdominal pain, vomiting and conjunctivitis were associated with poor prognosis for EVD patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0195-9) contains supplementary material, which is available to authorized users.",2016 Nov 3,"['Ji, Ying-Jie', 'Duan, Xue-Zhang', 'Gao, Xu-Dong', 'Li, Lei', 'Li, Chen', 'Ji, Dong', 'Li, Wen-Gang', 'Wang, Li-Fu', 'Meng, Yu-Hua', 'Yang, Xiao', 'Ling, Bin-Fang', 'Song, Xue-Ai', 'Gu, Mei-Lei', 'Jiang, Tao', 'Koroma, She-Ku M.', 'Bangalie, James', 'Duan, Hui-Juan']",Infect Dis Poverty,,,False
4fd6ce6a0e0f551a80d019b4c9b6c25279605d91,PMC,"Clinical presentations and outcomes of patients with Ebola virus disease in Freetown, Sierra Leone",http://dx.doi.org/10.1186/s40249-016-0195-9,PMC5094140,27806732,CC BY,"BACKGROUND: Clinical and laboratory data were collected and analysed from patients with Ebola virus disease (EVD) in Jui Government Hospital in Freetown, Sierra Leone, where patients with EVD were received and/or treated from October 1, 2014 to March 21, 2015 during the West Africa EVD outbreak. METHODS: The study admitted 285 patients with confirmed EVD and followed them up till the endpoint (recovery or death). EVD was confirmed by quantitative RT-PCR assays detecting blood Ebola virus (EBOV). RESULTS: Among the 285 lab-confirmed EVD cases in Jui Government Hospital, 146 recovered and 139 died, with an overall survival rate of 51.23 %. Patients under the age of 6 years had a lower survival rate (37.50 %). Most non-survivors (79.86 %) died within 7 days after admission and the mean hospitalization time for non-survivors was 5.56 ± 6.11 days. More than half survivors (63.69 %) turned blood EBOV negative within 3 weeks after admission and the mean hospitalization time for survivors was 20.38 ± 7.58 days. High blood viral load (≥10(6) copies/ml) was found to be predictive of the non-survival outcome as indicated by the Receiver Operating Characteristic (ROC) curve analysis. The probability of patients’ survival was less than 15 % when blood viral load was greater than 10(6) copies/ml. Multivariate analyses showed that blood viral load (P = 0.005), confusion (P = 0.010), abdominal pain (P = 0.003), conjunctivitis (P = 0.035), and vomiting (P = 0.004) were factors independently associated with the outcomes of EVD patients. CONCLUSIONS: Most death occurred within 1 week after admission, and patients at the age of 6 or younger had a lower survival rate. Most surviving patients turned blood EBOV negative within 1–4 weeks after admission. Factors such as high blood viral load, confusion, abdominal pain, vomiting and conjunctivitis were associated with poor prognosis for EVD patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0195-9) contains supplementary material, which is available to authorized users.",2016 Nov 3,"['Ji, Ying-Jie', 'Duan, Xue-Zhang', 'Gao, Xu-Dong', 'Li, Lei', 'Li, Chen', 'Ji, Dong', 'Li, Wen-Gang', 'Wang, Li-Fu', 'Meng, Yu-Hua', 'Yang, Xiao', 'Ling, Bin-Fang', 'Song, Xue-Ai', 'Gu, Mei-Lei', 'Jiang, Tao', 'Koroma, She-Ku M.', 'Bangalie, James', 'Duan, Hui-Juan']",Infect Dis Poverty,,,True
202f004261b2489f0e28acebc96cba9ebb576860,PMC,Recombinase polymerase amplification assay for rapid detection of lumpy skin disease virus,http://dx.doi.org/10.1186/s12917-016-0875-5,PMC5094145,27806722,CC BY,"BACKGROUND: Lumpy skin disease virus (LSDV) is a Capripoxvirus infecting cattle and Buffalos. Lumpy skin disease (LSD) leads to significant economic losses due to hide damage, reduction of milk production, mastitis, infertility and mortalities (10 %). Early detection of the virus is crucial to start appropriate outbreak control measures. Veterinarians rely on the presence of the characteristic clinical signs of LSD. Laboratory diagnostics including virus isolation, sequencing and real-time polymerase chain reaction (PCR) are performed at well-equipped laboratories. In this study, a portable, simple, and rapid recombinase polymerase amplification (RPA) assay for the detection of LSDV-genome for the use on farms was developed. RESULTS: The LSDV RPA assay was performed at 42 °C and detected down to 179 DNA copies/reaction in a maximum of 15 min. Unspecific amplification was observed with neither LSDV-negative samples (n = 12) nor nucleic acid preparations from orf virus, bovine papular stomatitis virus, cowpoxvirus, Peste des petits ruminants and Blue tongue virus (serotypes 1, 6 and 8). The clinical sensitivity of the LSDV RPA assay matched 100 % (n = 22) to real-time PCR results. In addition, the LSDV RPA assay detected sheep and goat poxviruses. CONCLUSION: The LSDV RPA assay is a rapid and sensitive test that could be implemented in field or at quarantine stations for the identification of LSDV infected case. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0875-5) contains supplementary material, which is available to authorized users.",2016 Nov 2,"['Shalaby, Mohamed A.', 'El-Deeb, Ayman', 'El-Tholoth, Mohamed', 'Hoffmann, Donata', 'Czerny, Claus-Peter', 'Hufert, Frank T.', 'Weidmann, Manfred', 'Abd El Wahed, Ahmed']",BMC Vet Res,,,True
befd47f9dd7e050dcd46f483ca8e7bd902f4707f,PMC,A Comparative Study of Clinical Presentation and Risk Factors for Adverse Outcome in Patients Hospitalised with Acute Respiratory Disease Due to MERS Coronavirus or Other Causes,http://dx.doi.org/10.1371/journal.pone.0165978,PMC5094725,27812197,CC BY,"Middle East Respiratory syndrome (MERS) first emerged in Saudi Arabia in 2012 and remains a global health concern. The objective of this study was to compare the clinical features and risk factors for adverse outcome in patients with RT-PCR confirmed MERS and in those with acute respiratory disease who were MERS-CoV negative, presenting to the King Fahad Medical City (KFMC) in Riyadh between October 2012 and May 2014. The demographics, clinical and laboratory characteristics and clinical outcomes of patients with RT-PCR confirmed MERS-CoV infection was compared with those testing negative MERS-CoV PCR. Health care workers (HCW) with MERS were compared with MERS patients who were not health care workers. One hundred and fifty nine patients were eligible for inclusion. Forty eight tested positive for MERS CoV, 44 (92%) being hospital acquired infections and 23 were HCW. There were 111 MERS-CoV negative patients with acute respiratory illnesses included in this study as “negative controls”. Patient with confirmed MERS-CoV infection were not clinically distinguishable from those with negative MERS-CoV RT-PCR results although diarrhoea was commoner in MERS patients. A high level of suspicion in initiating laboratory tests for MERS-CoV is therefore indicated. Variables associated with adverse outcome were older age and diabetes as a co-morbid illness. Interestingly, co-morbid illnesses other than diabetes were not significantly associated with poor outcome. Health care workers with MERS had a markedly better clinical outcome compared to non HCW MERS patients.",2016 Nov 3,"['Garbati, Musa A.', 'Fagbo, Shamsudeen F.', 'Fang, Vicky J.', 'Skakni, Leila', 'Joseph, Mercy', 'Wani, Tariq A.', 'Cowling, Benjamin J.', 'Peiris, Malik', 'Hakawi, Ahmed']",PLoS One,,,True
605669a3876e7ff3961f0cca4c58a7059144d0ba,PMC,Waiting time to infectious disease emergence,http://dx.doi.org/10.1098/rsif.2016.0540,PMC5095216,27798277,CC BY,"Emerging diseases must make a transition from stuttering chains of transmission to sustained chains of transmission, but this critical transition need not coincide with the system becoming supercritical. That is, the introduction of infection to a supercritical system results in a significant fraction of the population becoming infected only with a certain probability. Understanding the waiting time to the first major outbreak of an emerging disease is then more complicated than determining when the system becomes supercritical. We treat emergence as a dynamic bifurcation, and use the concept of bifurcation delay to understand the time to emergence after a system becomes supercritical. Specifically, we consider an SIR model with a time-varying transmission term and random infections originating from outside the population. We derive an analytic density function for the delay times and find it to be, in general, in agreement with stochastic simulations. We find the key parameters to be the rate of introduction of infection and the rate of change of the basic reproductive ratio. These findings aid our understanding of real emergence events, and can be incorporated into early-warning systems aimed at forecasting disease risk.",2016 Oct,"['Dibble, Christopher J.', ""O'Dea, Eamon B."", 'Park, Andrew W.', 'Drake, John M.']",J R Soc Interface,,,True
5f96f9d0f4775e4803ec0d9c0b3c181a40ea27ce,PMC,Waiting time to infectious disease emergence,http://dx.doi.org/10.1098/rsif.2016.0540,PMC5095216,27798277,CC BY,"Emerging diseases must make a transition from stuttering chains of transmission to sustained chains of transmission, but this critical transition need not coincide with the system becoming supercritical. That is, the introduction of infection to a supercritical system results in a significant fraction of the population becoming infected only with a certain probability. Understanding the waiting time to the first major outbreak of an emerging disease is then more complicated than determining when the system becomes supercritical. We treat emergence as a dynamic bifurcation, and use the concept of bifurcation delay to understand the time to emergence after a system becomes supercritical. Specifically, we consider an SIR model with a time-varying transmission term and random infections originating from outside the population. We derive an analytic density function for the delay times and find it to be, in general, in agreement with stochastic simulations. We find the key parameters to be the rate of introduction of infection and the rate of change of the basic reproductive ratio. These findings aid our understanding of real emergence events, and can be incorporated into early-warning systems aimed at forecasting disease risk.",2016 Oct,"['Dibble, Christopher J.', ""O'Dea, Eamon B."", 'Park, Andrew W.', 'Drake, John M.']",J R Soc Interface,,,True
1621345a6fa32695580f1455de8a7f6284a0f9e9,PMC,Association of Mannose-binding Lectin Polymorphisms with Tuberculosis Susceptibility among Chinese,http://dx.doi.org/10.1038/srep36488,PMC5095599,27812036,CC BY,"Tuberculosis (TB) is caused by infection of Mycobacterium tuberculosis. Host genetic variability is an important determinant of the risk of developing TB in humans. Although the association between MBL2 polymorphisms and TB has been studied in various populations, the results are controversial. In this study four functional single-nucleotide polymorphisms (SNPs, H/L, X/Y, P/Q and A/B) across the MBL2 gene were genotyped by direct DNA sequencing of PCR products in a case-control population of Chinese Han origin, consisting of 1,020 patients with pulmonary TB and 1,020 controls. We found that individuals carrying variant allele at A/B (namely BB or AB genotypes) was associated with increased susceptibility to TB (odds ratios [OR] = 1.57, 95% confidence interval [CI] 1.30–1.91, P = 1.3 × 10(−6)). Additionally, LYPB haplotype showed a significant association with increased risk of TB (OR = 1.54, 95% CI 1.27–1.87, P = 4.2 × 10(−6); global haplotype association P = 3.5 × 10(−5)). Furthermore, individuals bearing low- or medium- MBL expression haplotype pairs had an increased risk of TB (OR = 1.56, 95% CI 1.29–1.90, P = 1.4 × 10(−6)). Thus, the reduced expression of functional MBL secondary to having MBL2 variants may partially mediate the increased susceptibility to TB risk.",2016 Nov 4,"['Liu, Cheng', 'He, Tao', 'Rong, Yanxiao', 'Du, Fengjiao', 'Ma, Dongxing', 'Wei, Yujie', 'Mei, Zhiqin', 'Wang, Yuling', 'Wang, Haibin', 'Zhu, Yuehua', 'Zhang, Zongde', 'Zheng, Li', 'Wu, Xueqiong', 'Liu, Huiliang', 'Ding, Wenjun']",Sci Rep,,,True
e1cb86642107f15ec6d854bebf9c8341d1416ef4,PMC,Strand-Exchange Nucleic Acid Circuitry with Enhanced Thermo-and Structure- Buffering Abilities Turns Gene Diagnostics Ultra-Reliable and Environmental Compatible,http://dx.doi.org/10.1038/srep36605,PMC5095676,27812041,CC BY,"Catalytic hairpin assembly (CHA) is one of the most promising nucleic acid amplification circuits based on toehold-mediated strand exchange reactions. But its performance is usually ruined by fluctuated environmental temperatures or unexpected self-structures existing in most real-world targets. Here we present an amide-assistant mechanism that successfully reduces the prevalence of these problems for CHA and maximizes its thermo- and structure- buffering abilities. Such an organic amide-promoted CHA (shortened as OHT-CHA) can unprecedentedly amplify through 4 °C to 60 °C without rebuilding sequences or concerning target complexity. We are then for the first time able to employ it as a direct and universal signal booster for loop mediated isothermal reaction (LAMP). LAMP is one of the most promising point-of-care (POC) gene amplifiers, but has been hard to detect precisely due to structured products and haunted off-target amplicons. OHT-CHA guarantees a significant and reliable signal for LAMP reaction amplified from as little as 10(−19) M virus gene. And one single set of OHT-CHA is qualified to any detection requirement, either in real-time at LAMP running temperature (~60 °C), or at end-point on a POC photon counter only holding environmental temperatures fluctuating between 4 °C to 42 °C.",2016 Nov 4,"['Zhu, Zhentong', 'Tang, Yidan', 'Jiang, Yu Sherry', 'Bhadra, Sanchita', 'Du, Yan', 'Ellington, Andrew D.', 'Li, Bingling']",Sci Rep,,,True
8a0b13901e64c9c2b9c0449cdcd7411ae0f1eac4,PMC,Anvillea garcinii extract inhibits the oxidative burst of primary human neutrophils,http://dx.doi.org/10.1186/s12906-016-1411-7,PMC5095960,27809835,CC BY,"BACKGROUND: Anvillea garcinii Coss. & Durieu (Anv) plant is used as a traditional North African medicine against several diseases associated with inflammation. At inflammatory sites, reactive oxygen species (ROS) produced in excess by activated phagocyte NADPH oxidase (NOX2) can accentuate inflammatory responses. Thus, we investigated if Anv-water soluble polysaccharides could modulate primary human neutrophil oxidative burst in vitro. METHODS: Human neutrophils were isolated from fresh whole blood and O(2) (.-) generation was measured by cytochrome c reduction assays. Western blots were used to analyse the translocation of PKC, p47(phox) (a key component of NOX2 activity) to neutrophil plasma membrane. Also, myeloperoxidase (MPO) release in the extracellular medium was studied by western blots. Flow cytometric analysis was used to detect CD11b membrane expression. RESULTS: Water soluble polysaccharides from Anv dose-dependently inhibited N-formyl-methionyl-leucyl-phenylalanine (fMLF)- and phorbol myristate acetate (PMA)-induced O(2) (.-) generation by human neutrophils. Moreover, Anv-polysaccharides strongly inhibited PMA-induced PKCβ and p47(phox) translocation to membranes and p47(phox) phosphorylation on Ser328, a main PKC target. In contrast, polysaccharides extract from Zygophyllum gaetulum plant, which is also used as a traditional North African medicine against inflammatory diseases, was ineffective on this PKCβ-p47phox pathway. Further, Anv inhibited important neutrophil degranulation markers corresponding to myeloperoxidase (MPO) release and CD11b membrane expression. CONCLUSION: The process of down-regulating NADPH oxidase by polysaccharides extracts from Anv provides new insights into the mechanism of Anv’s anti-inflammatory actions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12906-016-1411-7) contains supplementary material, which is available to authorized users.",2016 Nov 3,"['Boukemara, Hanane', 'Hurtado-Nedelec, Margarita', 'Marzaioli, Viviana', 'Bendjeddou, Dalila', 'El Benna, Jamel', 'Marie, Jean-Claude']",BMC Complement Altern Med,,,True
6c26acf9ba8059cbd9caa58acb1a64538cfb7df9,PMC,Two Genetically Similar H9N2 Influenza A Viruses Show Different Pathogenicity in Mice,http://dx.doi.org/10.3389/fmicb.2016.01737,PMC5096341,27867373,CC BY,"H9N2 Avian influenza virus has repeatedly infected humans and other mammals, which highlights the need to determine the pathogenicity and the corresponding mechanism of this virus for mammals. In this study, we found two H9N2 viruses with similar genetic background but with different pathogenicity in mice. The A/duck/Nanjing/06/2003 (NJ06) virus was highly pathogenic for mice, with a 50% mouse lethal dose (MLD(50)) of 10(2.83) 50% egg infectious dose (EID(50)), whereas the A/duck/Nanjing/01/1999 (NJ01) virus was low pathogenic for mice, with a MLD(50) of >10(6.81) EID(50). Further studies showed that the NJ06 virus grew faster and reached significantly higher titers than NJ01 in vivo and in vitro. Moreover, the NJ06 virus induced more severe lung lesions, and higher levels of inflammatory cellular infiltration and cytokine response in lungs than NJ01 did. However, only 12 different amino acid residues (HA-K157E, NA-A9T, NA-R435K, PB2-T149P, PB2-K627E, PB1-R187K, PA-L548M, PA-M550L, NP-G127E, NP-P277H, NP-D340N, NS1-D171N) were found between the two viruses, and all these residues except for NA-R435K were located in the known functional regions involved in interaction of viral proteins or between the virus and host factors. Summary, our results suggest that multiple amino acid differences may be responsible for the higher pathogenicity of the NJ06 virus for mice, resulting in lethal infection, enhanced viral replication, severe lung lesions, and excessive inflammatory cellular infiltration and cytokine response in lungs. These observations will be helpful for better understanding the pathogenic potential and the corresponding molecular basis of H9N2 viruses that might pose threats to human health in the future.",2016 Nov 4,"['Liu, Qingtao', 'Liu, Yuzhuo', 'Yang, Jing', 'Huang, Xinmei', 'Han, Kaikai', 'Zhao, Dongmin', 'Bi, Keran', 'Li, Yin']",Front Microbiol,,,True
9c6df064dc7aedea41eca964a69131e37f330f6b,PMC,"Enterovirus D-68 Infection, Prophylaxis, and Vaccination in a Novel Permissive Animal Model, the Cotton Rat (Sigmodon hispidus)",http://dx.doi.org/10.1371/journal.pone.0166336,PMC5096705,27814404,CC BY,"In recent years, there has been a significant increase in detection of Enterovirus D-68 (EV-D68) among patients with severe respiratory infections worldwide. EV-D68 is now recognized as a re-emerging pathogen; however, due to lack of a permissive animal model for EV-D68, a comprehensive understanding of the pathogenesis and immune response against EV-D68 has been hampered. Recently, it was shown that EV-D68 has a strong affinity for α2,6-linked sialic acids (SAs) and we have shown previously that α2,6-linked SAs are abundantly present in the respiratory tract of cotton rats (Sigmodon hispidus). Thus, we hypothesized that cotton rats could be a potential model for EV-D68 infection. Here, we evaluated the ability of two recently isolated EV-D68 strains (VANBT/1 and MO/14/49), along with the historical prototype Fermon strain (ATCC), to infect cotton rats. We found that cotton rats are permissive to EV-D68 infection without virus adaptation. The different strains of EV-D68 showed variable infection profiles and the ability to produce neutralizing antibody (NA) upon intranasal infection or intramuscular immunization. Infection with the VANBT/1 resulted in significant induction of pulmonary cytokine gene expression and lung pathology. Intramuscular immunization with live VANBT/1 or MO/14/49 induced strong homologous antibody responses, but a moderate heterologous NA response. We showed that passive prophylactic administration of serum with high content of NA against VANBT/1 resulted in an efficient antiviral therapy. VANBT/1-immunized animals showed complete protection from VANBT/1 challenge, but induced strong pulmonary Th1 and Th2 cytokine responses and enhanced lung pathology, indicating the generation of exacerbated immune response by immunization. In conclusion, our data illustrate that the cotton rat is a powerful animal model that provides an experimental platform to investigate pathogenesis, immune response, anti-viral therapies and vaccines against EV-D68 infection.",2016 Nov 4,"['Patel, Mira C.', 'Wang, Wei', 'Pletneva, Lioubov M.', 'Rajagopala, Seesandra V.', 'Tan, Yi', 'Hartert, Tina V.', 'Boukhvalova, Marina S.', 'Vogel, Stefanie N.', 'Das, Suman R.', 'Blanco, Jorge C. G.']",PLoS One,,,True
430e499fc7f67e711312d57680f20c15a235cb20,PMC,Deep Sequencing Analysis Reveals the Mycoviral Diversity of the Virome of an Avirulent Isolate of Rhizoctonia solani AG-2-2 IV,http://dx.doi.org/10.1371/journal.pone.0165965,PMC5096721,27814394,CC BY,"Rhizoctonia solani represents an important plant pathogenic Basidiomycota species complex and the host of many different mycoviruses, as indicated by frequent detection of dsRNA elements in natural populations of the fungus. To date, eight different mycoviruses have been characterized in Rhizoctonia and some of them have been reported to modulate its virulence. DsRNA extracts of the avirulent R. solani isolate DC17 (AG2-2-IV) displayed a diverse pattern, indicating multiple infections with mycoviruses. Deep sequencing analysis of the dsRNA extract, converted to cDNA, revealed that this isolate harbors at least 17 different mycovirus species. Based on the alignment of the conserved RNA-dependent RNA-polymerase (RdRp) domain, this viral community included putative members of the families Narnaviridae, Endornaviridae, Partitiviridae and Megabirnaviridae as well as of the order Tymovirales. Furthermore, viruses, which could not be assigned to any existing family or order, but showed similarities to so far unassigned species like Sclerotinia sclerotiorum RNA virus L, Rhizoctonia solani dsRNA virus 1, Aspergillus foetidus slow virus 2 or Rhizoctonia fumigata virus 1, were identified. This is the first report of a fungal isolate infected by 17 different viral species and a valuable study case to explore the diversity of mycoviruses infecting R. solani.",2016 Nov 4,"['Bartholomäus, Anika', 'Wibberg, Daniel', 'Winkler, Anika', 'Pühler, Alfred', 'Schlüter, Andreas', 'Varrelmann, Mark']",PLoS One,,,True
bf6534fa1d3e5b2c6c5be7382633d56c6b92dea5,PMC,Viral respiratory infections in a nursing home: a six-month prospective study,http://dx.doi.org/10.1186/s12879-016-1962-8,PMC5097393,27814689,CC BY,"BACKGROUND: The knowledge on viral respiratory infections in nursing home (NH) residents and their caregivers is limited. The purpose of the present study was to assess and compare the incidence of acute respiratory infections (ARI) in nursing home (NH) residents and staff, to identify viruses involved in ARI and to correlate viral etiology with clinical manifestations of ARI. METHODS: The prospective surveillance study was accomplished in a medium-sized NH in Slovenia (central Europe). Ninety NH residents and 42 NH staff were included. Nasopharyngeal swabs were collected from all participants at enrollment (December 5th, 2011) and at the end of the study (May 31st, 2012), and from each participant that developed ARI within this timeframe. Molecular detection of 15 respiratory viruses in nasopharyngeal swab samples was performed. RESULTS: The weekly incidence rate of ARI in NH residents and NH staff correlated; however, it was higher in staff members than in residents (5.9 versus 3.8/1,000 person-days, P = 0.03), and was 2.5 (95 % CI: 1.36–4.72) times greater in residents without dementia than in residents with dementia. Staff members typically presented with upper respiratory tract involvement, whereas in residents lower respiratory tract infections predominated. Respiratory viruses were detected in 55/100 ARI episodes. In residents, influenza A virus, respiratory syncytial virus, and human metapneumovirus were detected most commonly, whereas in NH staff rhinovirus and influenza A virus prevailed. 38/100 ARI episodes (30/56 in residents, 8/44 in staff) belonged to one of three outbreaks (caused by human metapneumovirus, influenza A virus and respiratory syncytial virus, respectively). NH residents had higher chances for virus positivity within outbreak than HN staff (OR = 7.4, 95 % CI: 1.73–31.48, P < 0.01). CONCLUSIONS: ARI are common among NH residents and staff, and viruses were detected in a majority of the episodes of ARI. Many ARI episodes among NH residents were outbreak cases and could be considered preventable. TRIAL REGISTRATION: The study was registered on the 1(th) of December 2011 at ClinicalTrials (NCT01486160).",2016 Nov 4,"['Uršič, Tina', 'Miksić, Nina Gorišek', 'Lusa, Lara', 'Strle, Franc', 'Petrovec, Miroslav']",BMC Infect Dis,,,True
5a4a0f630530c7225fd23178fbdfedd2dccf535c,PMC,Antibacterial Effects of Glycyrrhetinic Acid and Its Derivatives on Staphylococcus aureus,http://dx.doi.org/10.1371/journal.pone.0165831,PMC5098735,27820854,CC BY,"Staphylococcus aureus is a major pathogen in humans and causes serious problems due to antibiotic resistance. We investigated the antimicrobial effect of glycyrrhetinic acid (GRA) and its derivatives against 50 clinical S. aureus strains, including 18 methicillin-resistant strains. The minimum inhibitory concentrations (MICs) of GRA, dipotassium glycyrrhizate, disodium succinoyl glycyrrhetinate (GR-SU), stearyl glycyrrhetinate and glycyrrhetinyl stearate were evaluated against various S. aureus strains. Additionally, we investigated the bactericidal effects of GRA and GR-SU against two specific S. aureus strains. DNA microarray analysis was also performed to clarify the mechanism underlying the antibacterial activity of GR-SU. We detected the antimicrobial activities of five agents against S. aureus strains. GRA and GR-SU showed strong antibacterial activities compared to the other three agents tested. At a higher concentration (above 2x MIC), GRA and GR-SU showed bactericidal activity, whereas at a concentration of 1x MIC, they showed a bacteriostatic effect. Additionally, GRA and GR-SU exhibited a synergistic effect with gentamicin. The expression of a large number of genes (including transporters) and metabolic factors (carbohydrates and amino acids) was altered by the addition of GR-SU, suggesting that the inhibition of these metabolic processes may influence the degree of the requirement for carbohydrates or amino acids. In fact, the requirement for carbohydrates or amino acids was increased in the presence of either GRA or GR-SU. GRA and GR-SU exhibited strong antibacterial activity against several S. aureus strains, including MRSA. This activity may be partly due to the inhibition of several pathways involved in carbohydrate and amino acid metabolism.",2016 Nov 7,"['Oyama, Kentaro', 'Kawada-Matsuo, Miki', 'Oogai, Yuichi', 'Hayashi, Tetsuya', 'Nakamura, Norifumi', 'Komatsuzawa, Hitoshi']",PLoS One,,,True
a106bdc3abdca61cda30b7f968c388e320e547e3,PMC,A data-driven model for influenza transmission incorporating media effects,http://dx.doi.org/10.1098/rsos.160481,PMC5098988,27853563,CC BY,"Numerous studies have attempted to model the effect of mass media on the transmission of diseases such as influenza; however, quantitative data on media engagement has until recently been difficult to obtain. With the recent explosion of ‘big data’ coming from online social media and the like, large volumes of data on a population’s engagement with mass media during an epidemic are becoming available to researchers. In this study, we combine an online dataset comprising millions of shared messages relating to influenza with traditional surveillance data on flu activity to suggest a functional form for the relationship between the two. Using this data, we present a simple deterministic model for influenza dynamics incorporating media effects, and show that such a model helps explain the dynamics of historical influenza outbreaks. Furthermore, through model selection we show that the proposed media function fits historical data better than other media functions proposed in earlier studies.",2016 Oct 26,"['Mitchell, Lewis', 'Ross, Joshua V.']",R Soc Open Sci,,,True
553190ac565fa3e5a93c4e52fb9d19157515ca06,PMC,A data-driven model for influenza transmission incorporating media effects,http://dx.doi.org/10.1098/rsos.160481,PMC5098988,27853563,CC BY,"Numerous studies have attempted to model the effect of mass media on the transmission of diseases such as influenza; however, quantitative data on media engagement has until recently been difficult to obtain. With the recent explosion of ‘big data’ coming from online social media and the like, large volumes of data on a population’s engagement with mass media during an epidemic are becoming available to researchers. In this study, we combine an online dataset comprising millions of shared messages relating to influenza with traditional surveillance data on flu activity to suggest a functional form for the relationship between the two. Using this data, we present a simple deterministic model for influenza dynamics incorporating media effects, and show that such a model helps explain the dynamics of historical influenza outbreaks. Furthermore, through model selection we show that the proposed media function fits historical data better than other media functions proposed in earlier studies.",2016 Oct 26,"['Mitchell, Lewis', 'Ross, Joshua V.']",R Soc Open Sci,,,False
20af160641510a4c79b9a23b06ea83d27ebba059,PMC,The nucleolar protein GLTSCR2 is required for efficient viral replication,http://dx.doi.org/10.1038/srep36226,PMC5099953,27824081,CC BY,"Glioma tumor suppressor candidate region gene 2 protein (GLTSCR2) is a nucleolar protein. In the investigation of the role of GLTSCR2 that played in the cellular innate immune response to viral infection, we found GLTSCR2 supported viral replication of rhabdovirus, paramyxovirus, and coronavirus in cells. Viral infection induced translocation of GLTSCR2 from nucleus to cytoplasm that enabled GLTSCR2 to attenuate type I interferon IFN-β and support viral replication. Cytoplasmic GLTSCR2 was able to interact with retinoic acid-inducible gene I (RIG-I) and the ubiquitin-specific protease 15 (USP15), and the triple interaction induced USP15 activity to remove K63-linked ubiquitination of RIG-I, leading to attenuation of RIG-I and IFN-β. Blocking cytoplasmic translocation of GLTSCR2, by deletion of its nuclear export sequence (NES), abrogated its ability to attenuate IFN-β and support viral replication. GLTSCR2-mediated attenuation of RIG-I and IFN-β led to alleviation of host cell innate immune response to viral infection. Our findings suggested that GLTSCR2 contributed to efficient viral replication, and GLTSCR2 should be considered as a potential target for therapeutic control of viral infection.",2016 Nov 8,"['Wang, Peng', 'Meng, Wen', 'Han, Shi-Chong', 'Li, Cui-Cui', 'Wang, Xiao-Jun', 'Wang, Xiao-Jia']",Sci Rep,,,True
73c97b301049429f21da128565e117ee1d368046,PMC,Brain on FIRES: Super Refractory Seizure in a 7 yr Old Boy,,PMC5100042,27843471,CC BY,"We present a 7 yr old boy afflicted with super-refractory seizure that responded poorly to antiepileptic drugs and sustained a long course of hospitalization and complications of high doses of medications as well as longstanding stay in hospital. The differential diagnoses were, fever-induced refractory epileptic encephalopathy (FIRES), and infectious and autoimmune encephalitis. However, work-ups had not revealed any evidence of any specific diagnosis, so we assumed that he was afflicted by viral infectious encephalitis as he had, fever, vomiting, and prodromal symptoms of infectious (most probably viral) disease prior to onset of the seizure attacks.",2016 Autumn,"['Tavasoli, Alireza', 'GHARIB, Behdad', 'ALIZADEH, Houman', 'FARSHADMOGHADDAM, Hossein', 'MEMARIAN, Sara', 'ASHRAFI, Mahmoodreza', 'SHARIFZADE, Meisam']",Iran J Child Neurol,,,True
36767ebe8e566a75a7fe9561206af5e722006b46,PMC,"Inosine pranobex is safe and effective for the treatment of subjects with confirmed acute respiratory viral infections: analysis and subgroup analysis from a Phase 4, randomised, placebo-controlled, double-blind study",http://dx.doi.org/10.1186/s12879-016-1965-5,PMC5100179,27821093,CC BY,"BACKGROUND: Inosine pranobex (Isoprinosine®) is an immunomodulatory drug approved in several countries for the treatment of viral infections. This study compared the efficacy and safety of inosine pranobex versus placebo in subjects with clinically diagnosed influenza-like illness, including subjects with laboratory-confirmed acute respiratory viral infections. Subgroup analyses evaluated the efficacy of inosine pranobex compared to placebo in otherwise healthy (without related ongoing disease) subjects that were less than 50 years of age and healthy subjects that were at least 50 years of age. The effect of body mass index (BMI) was evaluated in subjects less than 50 years of age. METHODS: A total of 463 subjects were randomly assigned to receive inosine pranobex (n = 231) or placebo (n = 232) in this Phase 4, randomised, double-blind, multicentre study. The primary efficacy endpoint was time to resolution of all influenza-like symptoms present at baseline to none. Safety was evaluated through analysis of adverse events, vital signs, and physical examinations. RESULTS: The difference in time to resolution of all influenza-like symptoms between treatment groups was not statistically significant but showed a faster improvement in subjects in the inosine pranobex group versus those in the placebo group - Hazard Ratio = 1.175; (95 % CI: 0.806–1.714). P-value = 0.324. In the subgroup analysis for subjects less than 50 years of age, statistically significant differences in time to resolution of influenza-like symptoms that favoured the inosine pranobex group over the placebo group were observed in those without related ongoing disease and those who were non-obese (BMI <30 kg/m(2)). The differences between the inosine pranobex and placebo groups in subjects at least 50 years of age without related ongoing disease and in subjects less than 50 years of age who were obese (BMI ≥30 kg/m(2)) were not statistically significant. Inosine pranobex was generally well tolerated, and no deaths were reported. CONCLUSIONS: The study results indicate the safety of inosine pranobex for the treatment of subjects with confirmed acute respiratory viral infections and confirm the efficacy of inosine pranobex versus placebo in healthy non-obese subjects less than 50 years of age with clinically diagnosed influenza-like illnesses. TRIAL REGISTRATION: EWO-ISO-2014/1, EudraCT 2014-001863-11; Date of registration: 29 APR 2014; Detail information web link: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001863-11/results ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1965-5) contains supplementary material, which is available to authorized users.",2016 Nov 7,"['Beran, Jiří', 'Šalapová, Eva', 'Špajdel, Marian', None]",BMC Infect Dis,,,True
10978f83e192204ea4f2347d49886969558a8b99,PMC,Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization,http://dx.doi.org/10.7554/eLife.17636,PMC5101012,27692070,CC BY,"Viral replicase recruitment and long-range RNA interactions are essential for RNA virus replication, yet the mechanism of their interplay remains elusive. Flaviviruses include numerous important human pathogens, e.g., dengue virus (DENV) and Zika virus (ZIKV). Here, we revealed a highly conserved, conformation-tunable cis-acting element named 5′-UAR-flanking stem (UFS) in the flavivirus genomic 5′ terminus. We demonstrated that the UFS was critical for efficient NS5 recruitment and viral RNA synthesis in different flaviviruses. Interestingly, stabilization of the DENV UFS impaired both genome cyclization and vRNA replication. Moreover, the UFS unwound in response to genome cyclization, leading to the decreased affinity of NS5 for the viral 5′ end. Thus, we propose that the UFS is switched by genome cyclization to regulate dynamic RdRp binding for vRNA replication. This study demonstrates that the UFS enables communication between flavivirus genome cyclization and RdRp recruitment, highlighting the presence of switch-like mechanisms among RNA viruses. DOI: http://dx.doi.org/10.7554/eLife.17636.001",,"['Liu, Zhong-Yu', 'Li, Xiao-Feng', 'Jiang, Tao', 'Deng, Yong-Qiang', 'Ye, Qing', 'Zhao, Hui', 'Yu, Jiu-Yang', 'Qin, Cheng-Feng']",eLife.; 5:e17636,,,True
4f2e6240097fc7f8699ec07c84d37bbc8a15310c,PMC,Acyclic nucleoside phosphonates containing the amide bond,http://dx.doi.org/10.1007/s00706-016-1848-x,PMC5101293,27881885,CC BY,"ABSTRACT: To study the influence of a linker rigidity and donor–acceptor properties, the P–CH(2)–O–CHR– fragment in acyclic nucleoside phosphonates (e.g., acyclovir, tenofovir) was replaced by the P–CH(2)–HN–C(O)– residue. The respective phosphonates were synthesized in good yields by coupling the straight chain of ω-aminophosphonates and nucleobase-derived acetic acids with EDC. Based on the (1)H and (13)C NMR data, the unrestricted rotation within the methylene and 1,2-ethylidene linkers in phosphonates from series a and b was confirmed. For phosphonates containing 1,3-propylidene (series c) fragments, antiperiplanar disposition of the bulky O,O-diethylphosphonate and substituted amidomethyl groups was established. The synthesized ANPs P–X–HNC(O)–CH(2)B (X = CH(2), CH(2)CH(2), CH(2)CH(2)CH(2), CH(2)OCH(2)CH(2)) appeared inactive in antiviral assays against a wide variety of DNA and RNA viruses at concentrations up to 100 μM while marginal antiproliferative activity (L1210 cells, IC(50) = 89 ± 16 μM and HeLa cells, IC(50) = 194 ± 19 μM) was noticed for the analog derived from (5-fluorouracyl-1-yl)acetic acid and O,O-diethyl (2-aminoethoxy)methylphosphonate. GRAPHICAL ABSTRACT: [Image: see text]",2016 Oct 26,"['Głowacka, Iwona E.', 'Piotrowska, Dorota G.', 'Andrei, Graciela', 'Schols, Dominique', 'Snoeck, Robert', 'Wróblewski, Andrzej E.']",Monatsh Chem,,,True
281ed09feadb379021bb0d63faa25b484ca482f1,PMC,Predictors of recovery from post-traumatic stress disorder after the dongting lake flood in China: a 13–14 year follow-up study,http://dx.doi.org/10.1186/s12888-016-1097-x,PMC5101704,27825328,CC BY,"BACKGROUND: Floods are some of the most common and destructive natural disasters in the world, potentially leading to both physical injuries and psychological disorders, including post-traumatic stress disorder (PTSD). PTSD can damage functional capacity and interfere with social functioning. However, little is known about recovery from PTSD after floods. This study used 2013–2014 follow-up data on survivors of the 1998 Dongting Lake flood who were diagnosed with PTSD in 2000 to measure the prevalence rate of PTSD at follow-up and identify predictors of recovery from the PTSD diagnosis in 2000. METHODS: Participants included survivors who had been diagnosed as having PTSD in 2000 after the 1998 Dongting Lake flood. PTSD at follow-up was reassessed using the PTSD Checklist-Civilian version. Information on demographics, trauma-related stressors, post-trauma stressors, social support, and coping style were collected through face-to-face interviews. The association between the independent variables and PTSD at follow-up was analyzed using logistic regression analyses. RESULTS: A total of 201 participants with a PTSD diagnosis in 2000 were included in this study. A total of 19.4 % of the flood survivors with PTSD in 2000 continued to suffer from PTSD in 2013–2014. In the multivariable logistic regression model, individuals who had lost relatives (OR = 12.37, 95 % CI = 2.46–62.16), suffered from bodily injury (OR = 5.01, 95 % CI = 1.92–13.08), had a low level of social support (OR = 5.47, 95 % CI = 1.07–27.80), or had a negative coping style (OR = 4.92, 95 % CI = 1.89–12.81) were less likely to recover from PTSD. CONCLUSIONS: The prevalence rate of PTSD at follow-up indicates that natural disasters such as floods may have a negative influence on survivors’ mental health for an extended period of time. Individuals who have lost relatives, suffered from bodily injury, had a low level of social support, or had a negative coping style were less likely to recover from PTSD. Therefore, effective psychological intervention measures are necessary for facilitating the recovery process from PTSD, especially for individuals with adverse prognostic factors.",2016 Nov 8,"['Dai, Wenjie', 'Wang, Jieru', 'Kaminga, Atipatsa C.', 'Chen, Long', 'Tan, Hongzhuan', 'Lai, Zhiwei', 'Deng, Jing', 'Liu, Aizhong']",BMC Psychiatry,,,True
00ccc4ef2b6c6f238836b7feb5123bd6a822cc08,PMC,Involvement of the different lung compartments in the pathogenesis of pH1N1 influenza virus infection in ferrets,http://dx.doi.org/10.1186/s13567-016-0395-0,PMC5101722,27825367,CC BY,"Severe cases after pH1N1 infection are consequence of interstitial pneumonia triggered by alveolar viral replication and an exacerbated host immune response, characterized by the up-regulation of pro-inflammatory cytokines and the influx of inflammatory leukocytes to the lungs. Different lung cell populations have been suggested as culprits in the unregulated innate immune responses observed in these cases. This study aims to clarify this question by studying the different induction of innate immune molecules by the distinct lung anatomic compartments (vascular, alveolar and bronchiolar) of ferrets intratracheally infected with a human pH1N1 viral isolate, by means of laser microdissection techniques. The obtained results were then analysed in relation to viral quantification in the different anatomic areas and the histopathological lesions observed. More severe lung lesions were observed at 24 h post infection (hpi) correlating with viral antigen detection in bronchiolar and alveolar epithelial cells. However, high levels of viral RNA were detected in all anatomic compartments throughout infection. Bronchiolar areas were the first source of IFN-α and most pro-inflammatory cytokines, through the activation of RIG-I. In contrast, vascular areas contributed with the highest induction of CCL2 and other pro-inflammatory cytokines, through the activation of TLR3. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0395-0) contains supplementary material, which is available to authorized users.",2016 Nov 8,"['Vidaña, Beatriz', 'Martínez, Jorge', 'Martorell, Jaime', 'Montoya, María', 'Córdoba, Lorena', 'Pérez, Mónica', 'Majó, Natàlia']",Vet Res,,,True
aee43bea8ff949773e7d22ebbfd6304c20c2a76d,PMC,Discovery and Partial Genomic Characterisation of a Novel Nidovirus Associated with Respiratory Disease in Wild Shingleback Lizards (Tiliqua rugosa),http://dx.doi.org/10.1371/journal.pone.0165209,PMC5102451,27828982,CC BY,"A respiratory disease syndrome has been observed in large numbers of wild shingleback lizards (Tiliqua rugosa) admitted to wildlife care facilities in the Perth metropolitan region of Western Australia. Mortality rates are reportedly high without supportive treatment and care. Here we used next generation sequencing techniques to screen affected and unaffected individuals admitted to Kanyana Wildlife Rehabilitation Centre in Perth between April and December 2015, with the resultant discovery of a novel nidovirus significantly associated with cases of respiratory disease according to a case definition based on clinical signs. Interestingly this virus was also found in 12% of apparently healthy individuals, which may reflect testing during the incubation period or a carrier status, or it may be that this agent is not causative in the disease process. This is the first report of a nidovirus in lizards globally. In addition to detection of this virus, characterisation of a 23,832 nt segment of the viral genome revealed the presence of characteristic nidoviral genomic elements providing phylogenetic support for the inclusion of this virus in a novel genus alongside Ball Python nidovirus, within the Torovirinae sub-family of the Coronaviridae. This study highlights the importance of next generation sequencing technologies to detect and describe emerging infectious diseases in wildlife species, as well as the importance of rehabilitation centres to enhance early detection mechanisms through passive and targeted health surveillance. Further development of diagnostic tools from these findings will aid in detection and control of this agent across Australia, and potentially in wild lizard populations globally.",2016 Nov 9,"['O’Dea, Mark A.', 'Jackson, Bethany', 'Jackson, Carol', 'Xavier, Pally', 'Warren, Kristin']",PLoS One,,,True
b0cedaf41c2c857fcc792117c6bb3df1a87bc544,PMC,Interferon-Stimulated Gene 15 Conjugation Stimulates Hepatitis B Virus Production Independent of Type I Interferon Signaling Pathway In Vitro,http://dx.doi.org/10.1155/2016/7417648,PMC5102744,27867263,CC BY,"Hepatitis B virus (HBV) is an important account of infectious hepatitis and interferon (IFN) remains one of the best treatment options. Activation of type I IFN signaling pathway leads to expressions of IFN-stimulated genes (ISGs) which play important roles in antiviral and immunomodulatory responses to HBV or hepatitis C virus (HCV) infection. Our previous studies indicated that ISG15 and its conjugation (ISGylation) were exploited by HCV to benefit its replication and persistent infection. This study was designed to assess the role of ISG15 and ISGylation in HBV infection in vitro. The levels of ISG15 and ISGylation were upregulated by ISG15 plasmid transfection into HepG2.2.15 cells. Decreased ISGylation was achieved by siRNA targeting UBE1L, the only E1 activating enzyme for ISGylation. Overexpression of ISG15 and subsequent ISGylation significantly increased the levels of HBV DNA in the culture supernatants although the intracellular viral replication remained unaffected. Silencing UBE1L, with decreased ISGylation achieved, abrogated this ISGylation-mediated promoting effect. Our data indicated that overexpression of ISG15 stimulated HBV production in an ISGylation-dependent manner. Identification of ISG15-conjugated proteins (either HBV viral or host proteins) may reveal promising candidates for further antiviral drug development.",2016 Oct 27,"['Li, Yujia', 'Li, Shilin', 'Duan, Xiaoqiong', 'Chen, Yanzhao', 'Jiao, Baihai', 'Ye, Haiyan', 'Yao, Min', 'Chen, Limin']",Mediators Inflamm,,,False
05e9af5c04c17b89fd8d65d62a381eb22e8316ed,PMC,Interferon-Stimulated Gene 15 Conjugation Stimulates Hepatitis B Virus Production Independent of Type I Interferon Signaling Pathway In Vitro,http://dx.doi.org/10.1155/2016/7417648,PMC5102744,27867263,CC BY,"Hepatitis B virus (HBV) is an important account of infectious hepatitis and interferon (IFN) remains one of the best treatment options. Activation of type I IFN signaling pathway leads to expressions of IFN-stimulated genes (ISGs) which play important roles in antiviral and immunomodulatory responses to HBV or hepatitis C virus (HCV) infection. Our previous studies indicated that ISG15 and its conjugation (ISGylation) were exploited by HCV to benefit its replication and persistent infection. This study was designed to assess the role of ISG15 and ISGylation in HBV infection in vitro. The levels of ISG15 and ISGylation were upregulated by ISG15 plasmid transfection into HepG2.2.15 cells. Decreased ISGylation was achieved by siRNA targeting UBE1L, the only E1 activating enzyme for ISGylation. Overexpression of ISG15 and subsequent ISGylation significantly increased the levels of HBV DNA in the culture supernatants although the intracellular viral replication remained unaffected. Silencing UBE1L, with decreased ISGylation achieved, abrogated this ISGylation-mediated promoting effect. Our data indicated that overexpression of ISG15 stimulated HBV production in an ISGylation-dependent manner. Identification of ISG15-conjugated proteins (either HBV viral or host proteins) may reveal promising candidates for further antiviral drug development.",2016 Oct 27,"['Li, Yujia', 'Li, Shilin', 'Duan, Xiaoqiong', 'Chen, Yanzhao', 'Jiao, Baihai', 'Ye, Haiyan', 'Yao, Min', 'Chen, Limin']",Mediators Inflamm,,,True
adc882dda7e73073791ae83afee7affd0d3e3793,PMC,Cytokine cascade and networks among MSM HIV seroconverters: implications for early immunotherapy,http://dx.doi.org/10.1038/srep36234,PMC5103227,27830756,CC BY,"The timing, intensity and duration of the cytokine cascade and reorganized interrelations in cytokine networks are not fully understood during acute HIV-1 infection (AHI). Using sequential plasma samples collected over three years post-infection in a cohort of MSM HIV-1 seroconvertors, we determined the early kinetics of cytokine levels during FiebigI-IV stages using Luminex-based multiplex assays. Cytokines were quantified and relationships between cytokines were assessed by Spearman correlation. Compared with HIV-negative MSM, HIV-infected individuals had significantly increased multiple plasma cytokines, including GM-CSF, IFN-α2, IL-12p70, IP-10 and VEGF, during both acute and chronic stages of infection. Furthermore, rapid disease progressors (RDPs) had earlier and more robust cytokine storms, compared with slow disease progressors (SDPs) (49.6 days vs. 74.9 days, respectively; 6.7-fold vs. 3.7-fold change of cytokines, respectively), suggesting the faster and stronger cytokine storm during AHI could promote disease progression. On the other hand, HIV-1 infection induced more interlocked cytokines network, establishing new strong correlations and imposing a higher rigidity. There were, respectively, 146 (44.9%) statistically significant correlations of cytokines in RDPs and 241 (74.2%) in SDPs (p < 0.001). This study suggests that immunomodulatory interventions aimed at controlling cytokine storm in AHI may be beneficial to slow eventual disease progression.",2016 Nov 10,"['Huang, Xiaojie', 'Liu, Xinchao', 'Meyers, Kathrine', 'Liu, Lihong', 'Su, Bin', 'Wang, Pengfei', 'Li, Zhen', 'Li, Lan', 'Zhang, Tong', 'Li, Ning', 'Chen, Hui', 'Li, Haiying', 'Wu, Hao']",Sci Rep,,,True
37aa23b999728b605b38892e8cedff6100c85a82,PMC,Cytokine cascade and networks among MSM HIV seroconverters: implications for early immunotherapy,http://dx.doi.org/10.1038/srep36234,PMC5103227,27830756,CC BY,"The timing, intensity and duration of the cytokine cascade and reorganized interrelations in cytokine networks are not fully understood during acute HIV-1 infection (AHI). Using sequential plasma samples collected over three years post-infection in a cohort of MSM HIV-1 seroconvertors, we determined the early kinetics of cytokine levels during FiebigI-IV stages using Luminex-based multiplex assays. Cytokines were quantified and relationships between cytokines were assessed by Spearman correlation. Compared with HIV-negative MSM, HIV-infected individuals had significantly increased multiple plasma cytokines, including GM-CSF, IFN-α2, IL-12p70, IP-10 and VEGF, during both acute and chronic stages of infection. Furthermore, rapid disease progressors (RDPs) had earlier and more robust cytokine storms, compared with slow disease progressors (SDPs) (49.6 days vs. 74.9 days, respectively; 6.7-fold vs. 3.7-fold change of cytokines, respectively), suggesting the faster and stronger cytokine storm during AHI could promote disease progression. On the other hand, HIV-1 infection induced more interlocked cytokines network, establishing new strong correlations and imposing a higher rigidity. There were, respectively, 146 (44.9%) statistically significant correlations of cytokines in RDPs and 241 (74.2%) in SDPs (p < 0.001). This study suggests that immunomodulatory interventions aimed at controlling cytokine storm in AHI may be beneficial to slow eventual disease progression.",2016 Nov 10,"['Huang, Xiaojie', 'Liu, Xinchao', 'Meyers, Kathrine', 'Liu, Lihong', 'Su, Bin', 'Wang, Pengfei', 'Li, Zhen', 'Li, Lan', 'Zhang, Tong', 'Li, Ning', 'Chen, Hui', 'Li, Haiying', 'Wu, Hao']",Sci Rep,,,False
250c1f24a22bcb81973ea532f8236838987e0872,PMC,"The 12th Edition of the Scientific Days of the National Institute for Infectious Diseases “Prof. Dr. Matei Bals” and the 12th National Infectious Diseases Conference: Bucharest, Romania. 23–25 November 2016",http://dx.doi.org/10.1186/s12879-016-1877-4,PMC5103241,,CC BY,"A1 The outcome of patients with recurrent versus non-recurrent pneumococcal meningitis in a tertiary health-care hospital in Bucharest Cristian-Mihail Niculae, Eliza Manea, Raluca Jipa, Simona Merisor, Ruxandra Moroti, Serban Benea, Adriana Hristea A2 Influence of bacteriophages on sessile Gram-positive and Gram-negative bacteria Alina Cristina Neguț, Oana Săndulescu, Anca Streinu-Cercel, Dana Mărculescu, Magdalena Lorena Andrei, Veronica Ilie, Marcela Popa, Coralia Bleotu, Carmen Chifiriuc, Mircea Ioan Popa, Adrian Streinu-Cercel A3 The utility of inflammatory biomarkers in the prognostic evaluation of septic patients – past, present and future Alina Orfanu, Cristina Popescu, Anca Leuștean, Remulus Catană, Anca Negru, Alexandra Badea, Radu Orfanu, Cătălin Tilișcan, Victoria Aramă, Ştefan Sorin Aramă A4 Etiologic and clinical features of bacterial meningitis in infants Constanța-Angelica Vișan, Anca-Cristina Drăgănescu, Anuța Bilașco, Camelia Kouris, Mădălina Merișescu, Magdalena Vasile, Diana-Maria Slavu, Sabina Vintilă, Endis Osman, Alina Oprea, Sabina Sandu, Monica Luminos A5 The diagnostic and prognostic role of neutrophil to lymphocyte count ratio in sepsis Alina Orfanu, Victoria Aramă, Ştefan Sorin Aramă, Anca Leuştean, Remulus Catană, Anca Negru, Gabriel Adrian Popescu, Cristina Popescu A6 Whooping cough in a HIV positive patient Ramona Georgiana Stanculete, Ana Vaduva Enoiu, Adelina Raluca Marinescu, Voichita Lazureanu A7 Cronobacter sakazakii sepsis in varicella patient Adelina-Raluca Marinescu, Alexandru Crișan, Voichița Lăzureanu, Virgil Musta, Narcisa Nicolescu, Ruxandra Laza A8 Anaerobes an underdiagnosed cause of prosthesis joint infection Anca-Ruxandra Negru, Daniela-Ioana Munteanu, Raluca Mihăilescu, Remulus Catană, Olga Dorobăț, Alexandru Rafila, Emilia Căpraru, Marius Niculescu, Rodica Marinescu, Olivera Lupescu, Vlad Predescu, Adrian Streinu-Cercel, Victoria Aramă, Daniela Tălăpan A9 Streptococcus pneumoniae meningitis presenting with normal CSF – case presentation Ramona Ștefania Popescu, Luminița Bradu, Dragoș Florea, Adrian Streinu-Cercel A10 Extrapulmonary manifestations of infection with Mycoplasma pneumoniae – study on 24 cases Daniela Anicuta Leca, Elena Bunea, Andra Teodor, Egidia Miftode A11 The molecular diagnosis of severe bacterial sepsis in pediatric population Mădălina Merișescu, Gheorghiță Jugulete, Adrian Streinu-Cercel, Dragoș Florea, Monica Luminos A12 Acute Staphylococcus aureus endocarditis with multiple septic complications in a patient with diabetes mellitus – case presentation Ramona Ștefania Popescu, Anamaria Dobrotă, Adina Ilie, Liliana Lucia Preoțescu A13 Is Streptococcus suis meningitis an under-diagnosed zoonosis? Adriana Hristea, Raluca Jipa, Nicoleta Irimescu, Irina Panait, Eliza Manea, Simona Merisor, Cristian Niculae, Daniela Tălăpan A14 Klebsiella pneumoniae isolated from blood. Antimicrobial resistance – past and present Liana Cătălina Gavriliu, Otilia Elisabeta Benea, Șerban Benea, Alexandru Rafila, Olga Dorobăț, Mona Popoiu A15 Antibiotics resistance in Staphylococcus aureus isolated from blood cultures Livia Dragonu, Augustin Cupşa, Iulian Diaconescu, Irina Niculescu, Lucian Giubelan, Florentina Dumitrescu, Andreea Cristina Stoian, Camelia Guţă, Simona Puiu A16 Predominance of CTX-M enzymes in extended-spectrum β-lactamase-producing Enterobacteriaceae in two hospitals of Quebec City Bunescu Irina, Marilyse Vallée, Ann Huletsky, Dominique K. Boudreau, Ève Bérubé, Richard Giroux, Jean Longtin, Yves Longtin, Michel G. Bergeron A17 Postoperative meningoencephalitis with Acinetobacter baumannii XDR – a therapeutic challenge - Case report Cleo Nicoleta Roșculeț, Dalila-Ana Toma, Catrinel Ciuca, Daniela Tălăpan, Cătălin Apostolescu, Andrei Rogoz, Andrei Stangaciu, Viorica Mitescu, Tudor Vladoiu, Doina Iovănescu A18 Septic arthritis with Burkholderia cepacia Michaela Oana, Simona Costin A19 A novel approach for managing hard-to-treat infections Alina Cristina Neguț, Oana Săndulescu, Anca Streinu-Cercel, Maria Magdalena Moțoi, Mircea Ioan Popa, Adrian Streinu-Cercel A20 Nineteen months surveillance for multidrug resistant organisms (MDRO) by detecting asymptomatic colonization Daniela Tălăpan, Olga Mihaela Dorobăț, Mona Popoiu, Alexandru Mihai, Doina Iovănescu, Cleo Roşculeț, Cătălin Apostolescu, Gabriel-Adrian Popescu, Adrian Abagiu, Ruxandra Moroti-Constantinescu, Adriana Hristea, Victoria Aramă, Otilia Benea, Mădălina Simoiu, Rodica Bacruban, Adrian Streinu-Cercel, Alexandru Rafila A21 Antimicrobial resistance of Gram-positive cocci isolated from clinical specimens in the National Institute of Infectious Diseases “Prof Dr. Matei Balș” between 2009–2015 Olga Mihaela Dorobăț, Daniela Tălăpan, Alexandru Mihai, Ioana Bădicuț, Mona Popoiu, Alina Borcan, Alexandru Rafila A22 The high percentage of carbapenem-resistant Gram-negative bacilli in Romania: an analysis and some proposals Gabriel Adrian Popescu A23 Etiological, clinical and therapeutic considerations on 78 cases of healthcare associated meningitis or ventriculitis admitted in the “Sf. Parascheva” infectious diseases clinical hospital, Iași, from 2011 to 2015 Mihnea Hurmuzache, Georgiana Enache, Alexandra Ciocan, Mircea Bararu, Madalina Popazu A24 Nosocomial infection dynamics in an Intensive Care Department – an overview (epidemiological and clinical monitoring, advanced therapeutic intervention). Doina Viorica Iovănescu, Cleo Nicoleta Roșculeț, Andrei Rogoz Cătălin Gabriel Apostolescu, Viorica Mitescu(,) Tudor Vladoiu, Dalila Toma, Catrinel Ciuca A25 Safety and efficacy of interferon free treatment in patients with HCV chronic hepatitis- experience of a single Internal Medicine center Laura Iliescu, Georgiana Minzala, Letitia Toma, Mihaela Baciu, Alina Tanase, Carmen Orban A26 Viusid in treatment of chronic viral hepatitis B and C Victor Pantea, Gheorghe Placinta, Valentin Cebotarescu, Lilia Cojuhari, Paulina Jimbei A27 The management of hyperbilirubinemia in HCV cirrhotic patients who underwent therapy with direct acting antivirals Cristina Popescu, Anca Leuștean, Cristina Dragomirescu, Alina Orfanu, Cristina Murariu, Laurențiu Stratan, Alexandra Badea, Cătălin Tilișcan, Daniela Munteanu, Raluca Năstase, Violeta Molagic, Mihaela Rădulescu, Remulus Catana, Victoria Aramă A28 The efficacy of ombitasvir-paritaprevir/ritonavir, dasabuvir and ribavirin in patients with genotype 1 HCV compensated cirrhosis Cristina Popescu, Laurențiu Stratan, Remulus Catana, Anca Leuștean, Cristina Dragomirescu, Alexandra Badea, Cristina Murariu, Raluca Năstase, Violeta Molagic, Daniela Munteanu, Cătălin Tilișcan, Mihaela Rădulescu, Alina Orfanu, Ioan Diaconu, Anca Negru, Iulia Bodosca, Violeta Niță, Victoria Aramă A29 The efficacy of direct acting antivirals regimen without ribavirin in HCV genotype 1b infected patients with compensated cirrhosis Anca Leuștean, Victoria Aramă, Alina Orfanu, Remulus Catana, Laurențiu Stratan, Cristina Dragomirescu, Cristina Murariu, Alexandra Badea, Cătălin Tilișcan, Daniela Munteanu, Violeta Molagic, Raluca Năstase, Mihaela Rădulescu, Cristina Popescu A30 Liver decompensation during ombitasvir-paritaprevir/ritonavir-dasabuvir and ribavirin regimen in HCV infected patients with Child-Pugh A cirrhosis Cristina Popescu, Cristina Dragomirescu, Anca Leuștean, Cristina Murariu, Laurențiu Stratan, Alexandra Badea, Remulus Catană, Alina Orfanu, Raluca Mihaela Năstase, Violeta Molagic, Daniela Munteanu, Cătălin Tilișcan, Victoria Aramă A31 The safety of direct acting antivirals in HCV compensated cirrhotic patients - an interim analysis Victoria Aramă, Remulus Catană, Cristina Dragomirescu, Cristina Murariu, Anca Leuștean, Laurențiu Stratan, Alexandra Badea, Alina Orfanu, Anca Negru, Raluca Năstase, Violeta Molagic, Daniela Munteanu, Cătălin Tilișcan, Mihaela Rădulescu, Ioan Diaconu, Violeta Niță, Iulia Bodoșca, Cristina Popescu A32 The access of patients with HCV compensated cirrhosis to the National Program of therapy with direct acting antivirals Cristina Popescu, Alexandra Badea, Anca Leuștean, Alina Orfanu, Anca Negru, Laurențiu Stratan, Cristina Dragomirescu, Remulus Catană, Cristina Murariu, Violeta Molagic, Raluca Năstase, Cătălin Tilișcan, Daniela Munteanu, Mihaela Rădulescu, Ioan Diaconu, Violeta Niță, Iulia Bodoșca, Victoria Aramă A33 Severe reactivation of chronic hepatitis B after discontinuation of nucleos(t)ide analogues – a case series Cristina Popescu, Alina Orfanu, Anca Leuștean, Alexandra Badea, Laurențiu Stratan, Remulus Catană, Cătălin Tilișcan, Victoria Aramă A34 The dynamic of hematological disorders during direct acting antivirals therapy for HCV compensated cirrhosis Cristina Popescu, Cristina Murariu, Cristina Dragomirescu, Anca Leuștean, Laurențiu Stratan, Alina Orfanu, Alexandra Badea, Remulus Catană, Anca Negru, Cătălin Tilișcan, Daniela Munteanu, Mihaela Rădulescu, Violeta Molagic, Raluca Mihaela Năstase, Ioan Alexandru Diaconu, Iulia Bodoșca, Violeta Niță, Victoria Aramă A35 Behaviors, attitudes and risk factors for viral hepatitis in international medical students vs. the general population in Romania Yagmur Erturk, Oana Săndulescu, Alina Cristina Neguț, Claudiu Mihai Șchiopu, Adrian Streinu-Cercel, Anca Streinu-Cercel A36 Characteristics of hepatitis C virus reactivation due to immunosuppressive therapy in Romanian HCV infected patients with hematological malignancies Violeta Molagic, Cătălin Tilișcan, Cristina Popescu, Raluca Mihăilescu, Daniela Munteanu, Raluca Năstase, Anca Negru, Angelica Tenita, Victoria Aramă, Ștefan Sorin Aramă A37 The dynamic IFN-gamma serum levels during successful peginterferon-a 2a/ribavirin therapy in HCV chronic infection Simona Alexandra Iacob, Diana Gabriela Iacob, Monica Luminos A38 Overlapping risk factors for transmission of HBV, HCV and HIV in the general population in Romania Anca Streinu-Cercel, Oana Săndulescu, Mioara Predescu, Alexandra Mărdărescu, Cătălin Tilișcan, Mihai Săndulescu, Claudiu Mihai Șchiopu, Adrian Streinu-Cercel A39 Acute hepatitis - an uncommon neurological complication Cleo Nicoleta Roșculeț, Catrinel Olimpia Ciuca, Dalila Ana Toma, Cătălin Gabriel Apostolescu, Andrei Rogoz, Cristina Elena Mitu, Andrei Stangaciu, Viorica Daniela Mitescu, Tudor Gheorghe Vladoiu, Doina Viorica Iovănescu A40 Regression of liver fibrosis following sustained virological response in patients with chronic HCV infection and cirrhosis Oana Săndulescu, Anca Streinu-Cercel, Monica Andreea Stoica, Liliana Lucia Preoțescu, Daniela Manolache, Gabriela Jana Ceapraga, Maria Magdalena Moțoi, Luminița Bradu, Adina Ilie, Gabriela Mircea, Ionel Durbală, Adrian Streinu-Cercel A41 Preliminary results of treatment with sofosbuvir and daclatasvir of patients with chronic hepatitis C Irina Russu, Tiberiu Holban, Tatiana Pantilimonov, Galina Chiriacov, Arcadie Macvovei, Elena Scorohodico, Oleg Dmitriev A42 HIV-syphilis coinfection Diana Alexandra Costache, Anca Benea, Eliza Manea, Cristian Niculae, Raluca Jipa, Adriana Hristea, Elisabeta Benea, Ruxandra Moroti, Șerban Benea A43 Thrombophilia – additional risk factor for the evolution of pregnancy in HIV-positive patients Mihai Mitran, Carmen Georgescu, Loredana Mitran, Simona Vladareanu A44 The incidence of oropharyngeal candidiasis in hospitalized HIV infected pediatric Romanian cohort between 1 January - 31 December 2015 Andreea Ioana Magirescu, Viorica Andreev, Cristina Nicolau, Alexandra Largu, Carmen Dorobat, Carmen Manciuc A45 TB incidence in HIV infected patients during the year of 2015 Viorica Andreev, Andreea Ioana Magirescu, Ina Isac, Cristina Nicolau, Alexandra Largu, Carmen Dorobat, Carmen Manciuc A46 Retrospective analysis of HIV/AIDS deaths recorded in the Clinical Infectious Diseases Hospital, Constanța in the period 01 January 2014–30 June 2016. Epidemiological considerations. Iulia Gabriela Șerban, Ghiulendan Resul, Consuela Marcaș A47 Acute liver failure with favorable evolution in an HIV-HBV coinfected patient Iosif Marincu, Patricia Poptelecan, Bogdan Trincă, Sorina Mitrescu, Anca Tudor, Daliborca Vlad, Livius Tirnea A48 Lifestyle impact on HIV management Nurcan Baydaroglu, Alina Cristina Neguț, Oana Săndulescu, Daniela Manolache, Gabriela Ceapraga, Monica Andreea Stoica, Anca Streinu-Cercel, Adrian Streinu-Cercel 49. HIV positive mothers newborns - clinical experience from January 2012 to June 2016 Carmen Manciuc, Mariana Pagute, Cristina Nicolau, Carmen Dorobăț, Alexandra Largu A50 Rediscovering HIV-associated progressive multifocal leukoencephalopathy and HIV encephalopathy: clinical suspicion and subsequent brain autopsies Ioan-Alexandru Diaconu, Laurențiu Stratan, Daniela Ion, Luciana Nichita, Cristina Popescu, Raluca Năstase, Daniela Munteanu, Violeta Molagic, Cătălin Tilișcan, Mihaela Rădulescu, Alexandra Diaconu, Anca Negru, Alina Orfanu, Cristina Dragomirescu, Remulus Catană, Anca Leuștean, Irina Duport-Dodot, Cristina Murariu, Iulia Bodoșca, Violeta Niță, Alexandra Badea, Victoria Aramă A51 Antenatal surveillance of pregnant women with risk behavior and its impact on mother-to-child HIV transmission in Romania Mariana Mărdărescu, Cristina Petre, Marieta Iancu, Rodica Ungurianu, Alina Cibea, Ruxandra Drăghicenoiu, Ana Maria Tudor, Delia Vlad, Sorin Petrea, Carina Matei, Dan Oțelea, Carmen Crăciun, Cristian Anghelina, Alexandra Mărdărescu A52 Noninvasive assessments (APRI, Fib-4, transient elastography) of fibrosis in patients with HIV and HIV/HBV infection Elena Dumea, Adrian Streinu-Cercel, Sorin Rugină, Lucian Cristian Petcu, Stela Halichidis, Simona Claudia Cambrea A53 Undetectable HIV viral load – the main goal in the management of HIV-infected patients Carmen Chiriac, Nina-Ioana Bodnar, Iringo-Erzsebet Zaharia-Kezdi, Cristina Gîrbovan, Andrea Incze, Anca Meda Georgescu A54 LPS serum levels and correlation with immunological, virological and clinical outcome in HIV infected patients Simona Alexandra Iacob, Diana Gabriela Iacob, Eugenia Panaitescu, Monica Luminos, Manole Cojocaru A55 LL37 human cathelicidin serum levels are positively correlated with IFN gamma and alanine aminotransferase level in HCV infection Simona Alexandra Iacob, Diana Gabriela Iacob, Monica Luminos A56 Early diagnosis of pulmonary tuberculosis in a non-compliant HIV/AIDS late presenter patient Vochita Laurențiu, Vochita Andreia, Opreanu Radu, Trinca Bogdan, Rosca Ovidiu, Marincu Iosif A57 Evolution of antiretroviral regimens in naϊve patients in 2016 Ramona Zamfir, Alina Angelescu, Alena Andreea Popa, Raluca Jipa, Ruxandra Moroti, Adriana Hristea, Liana Gavriliu, Șerban Benea, Elisabeta Benea A58 The unfavorable risk factors for HIV infected persons with positive blood cultures hospitalized at the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” in 2015 Alena-Andreea Popa, Georgeta Ducu, Daniela Camburu, Alina Cozma, Manuela Podani, Roxana Dumitriu, Liana Gavriliu, Șerban Benea, Elisabeta Benea A59 Epidemiological aspects of HIV infection in Oltenia region Andreea Cristina Stoian, Florentina Dumitrescu, Augustin Cupșa, Lucian Giubelan, Irina Niculescu, Loredana Ionescu, Livia Dragonu A60 HIV risk behaviors and prevalence among patients in methadone maintenance therapy (MMT) from Arena center, Bucharest Adrian Octavian Abagiu, Loredana Nicoleta Stoica, Catrinel Blaga, Archontis Koulosousas, Roxana Ștefănescu, Alice Atomoaie, Florentina Paraschiv, Florin Matache Duna A61 Therapeutic options in a case of severe psoriasis associated with both HIV infection and hepatitis C virus previously treated with fumaric acid esters Rodica Olteanu, Roxana Ion, Alexandra Zota, Isra Ennour Jaballah, Lara Mahfoud, Georgeta Preda, Magda Constantin A62 Prevalence of autoantibodies against gangliosides in asymptomatic HIV-infected patients Ilinca Nicolae, Corina Daniela Ene, Mădălina Irina Mitran, Vasile Benea, Mircea Tampa, Simona Roxana Georgescu A63 Subclinical inflammation in HIV-infected patients undergoing antiretroviral therapy – a cross sectional study Iulia Cristina Bodoșca, Cristina Murariu, Cătălin Tilișcan, Victoria Aramă, Cristina Popescu, Daniela Munteanu, Mihaela Rădulescu, Violeta Molagic, Raluca Năstase, Alina Orfanu, Anca Leuștean, Remulus Catană, Anca Negru, Adrian Streinu-Cercel, Sorin Aramă A64 Severe Guillain-Barré syndrome occurring after chickenpox with favorable evolution Iuliana CAramăngiu, Ovidiu Rosca, Monica Cialma, Radu Opreanu, Laurențiu Vochita, Iosif Marincu A65 Echovirus 30 infection with pulmonary and cardiac complications – case report Vlad Murărescu, Marilena Palaghiță, Alina Cristina Neguț, Cornel Camburu, Adrian Streinu-Cercel A66 Herpetic encephalitis with favorable evolution in an adult immunocompetent patient Irina Duşan, Patricia Poptelecan, Bogdan Trincă, Sorina Mitrescu, Livius Tirnea, Iosif Marincu A67 Clinical-evolutional aspects in present-day measles Narcisa Nicolescu, Alexandru Crișan, Voichița Lăzureanu, Ruxandra Laza, Virgil Musta, Adelina-Raluca Marinescu, Andreea Bîrlad A68 Pneumococcal superinfection in children with influenza Victor Daniel Miron, Anca Cristina Drăgănescu, Constanța-Angelica Vișan, Anuța Bilașco, Daniela Pițigoi, Oana Săndulescu, Monica Luminița Luminos A69 Varicella complicated with transverse myelitis - case presentation Monica Luminos, Endis Osman, Magdalena Vasile, Anca Cristina Drăgănescu, Constanța-Angelica Vișan, Anuța Bilașco, Camelia Kouris, Sabina Șchiopu, Mădălina Merișescu A70 Clinical forms of enterovirus infections during the summer season of 2016 Monica Luminos, Anca Cristina Drăgănescu, Constanța-Angelica Vișan, Anuța Bilașco, Camelia Kouris, Endis Osman, Sabina Vintilă, Magda Vasile, Mădălina Merișescu A71 Face off – HIV and lymphoma – case series presentation Liana Cătălina Gavriliu, Otilia Elisabeta Benea, Alina Angelescu, Ramona Zamfir, Daniela Camburu, Georgeta Ducu, Alina Cozma, Roxana Dumitriu, Manuela Podani, Șerban Benea, Mihaela Ionică A72 Coxsackie infection complicated by pancytopenia – pediatric case report Gheorghiță Jugulete, Adina Stăncescu, Cristina Elena Popescu, Luminița Marin, Diana Zaharia, Cristina Dumitrescu, Lucia Tudor, Sabina Vintilă A73 Viral respiratory infections in children in the season 2015–2016 Constanța-Angelica Vișan, Anca Cristina Drăgănescu, Anuța Bilașco, Magda Vasile, Mădălina Merișescu, Camelia Kouris, Cristina Negulescu, Endis Osman, Diana-Maria Slavu, Sabina Vintilă, Daniela Pițigoi, Monica Luminos A75 The severity of A H1N1 Influenza infection in the 2015–2016 season Cleo Roșculeț, Catrinel Olimpia Ciuca, Dalila Toma, Cătălin Apostolescu, Andrei Rogoz, Andrei Stangaciu, Viorica Mitescu, Doina Iovănescu, Cornel Camburu, Bogdana Manu A76 Acute respiratory distress syndrome in a child with measles Ana Vaduva-Enoiu, Ramona Georgiana Stanculete, Adelina Raluca Marinescu, Voichita Elena Lazureanu A77 Management challenges of right-sided infectious endocarditis in an HIV positive patient – case presentation Elena-Violeta Niță, Sînziana Dumitru, Daniela-Ioana Munteanu, Anca Ruxandra Negru, Remulus Catană, Ioan Diaconu, Bogdana Manu, Ligia Ionescu, Liliana Ion, Cătălin Tilișcan, Victoria Aramă A78 Bacterial infection in critical patients with severe A H1N1 influenza virus infection (epidemiology, development, therapeutic decisions) Doina Viorica Iovănescu, Cleo Nicoleta Roșculeț, Andrei Rogoz, Cătălin Apostolescu, Viorica Mitescu, Tudor Vladoiu, Dalila Toma, Catrinel Ciuca A79 Epidemiological aspects of severe acute respiratory infection cases (SARI) in the season 2015–2016, in the Clinical Hospital of Infectious Diseases – Constanța, Romania Iulia Gabriela Șerban, Marioara Neacșu A80Overexpression of IL-6 trans signaling pathway in viral infections Simona Roxana Georgescu, Vasile Benea, Corina Daniela Ene, Mircea Tampa, Cristina Iulia Mitran, Ilinca Nicolae A81 Acute viral hepatitis B with persistent HBsAg – description and evolution George Ciprian Pribac, Mirandolina Prisca, Fulvia Ursoiu, Carmen Neamtu, Bogdan Totolici, Coralia Cotoraci, Aurel Ardelean A82 Prevalence of cervical pathogens in a population of pregnant female patients monitored in a tertiary care hospital in Bucharest, Romania Simona Elena Albu, Mara Carsote, Beatrice Miclăuș, Diana Mihai, Oana Săndulescu, Cristina Vasiliu A83 Prevalence of group B Streptococcus during pregnancy in a cohort of patients monitored in a tertiary care hospital in Bucharest, Romania Cristina Vasiliu, Mara Carsote, Corina Gorgoi, Beatrice Miclăuș, Diana Mihai, Oana Săndulescu, Simona Elena Albu A84 Infectious hematoma in the gastrocnemius muscle – case presentation Amelia Blescun, Gelu Breaza A85 Reflections towards the underexplored HTLV Romanian viral circulation - adult T‐cell leukemia/lymphomas, a case series Sabina Vintila, Felicia Mihai, Meilin Omer, Cornel Dragan, Daniela Pitigoi A86 A febrile confusion syndrome with acute onset – case presentation Mirela Ciucu, Marius-Dan Ionescu, Cristina Roskanovic, Valentina Barbu, Iulian Diaconescu, Florentina Dumitrescu, Irina Niculescu A87 Retrobulbar optic neuritis in a HIV-positive patient - case report Mihaela Ionică, Ramona-Alexandra Zamfir, Alina Cozma, Otilia Elisabeta Benea A88 A rare presentation of Q fever – case presentation Alexandra-Sînziana Dumitru, Daniela-Ioana Munteanu, Violeta Niță, Cristina Popescu, Iulia Bodosca, Angelica Tenita, Viorica Ispas, Victoria Aramă A89 Tinea incognita – case presentation Vasile Benea, Simona Roxana Georgescu, Mircea Tampa, Diana Oana Leahu, Cristina Maria Safta, Mihaela Anca Benea A90 Incidence and risk factors associated with TORCH infections during pregnancy Oana Săndulescu, Octavian Munteanu, Roxana Bohâlțea, Livia Trașcă, Monica Cîrstoiu A91 Acute respiratory failure in critical patients with sepsis Doina Viorica Iovănescu, Cleo Nicoleta Roșculeț, Andrei Rogoz, Cătălin Gabriel Apostolescu, Viorica Daniela Mitescu, Tudor Gheorghe Vladoiu, Dalila Toma, Catrinel Ciuca A92 Cochleo-vestibular deficit secondary to Granulicatella elegans meningitis Mădălina Georgescu A93 Influenza 2015/2016 – clinical, epidemiological and virological characteristics of cases admitted in three infectious diseases hospitals Daniela Pițigoi, Alina Elena Ivanciuc, Mihaela Lazar, Teodora Ionescu, Carmen Maria Cherciu, Cristina Țecu, Maria Elena Mihai, Maria Nițescu, Rodica Bacruban, Delia Azamfire, Aura Dumitrescu, Elena Ianosik, Daniela Leca, Elena Duca, Andra Teodor, Codrina Bejan, Emanoil Ceaușu, Simin-Aysel Florescu, Corneliu Popescu, Grațiela Târdei, Codrina Juganariu, Emilia Lupulescu A94 Severe complications of varicella requiring hospitalization in previously healthy children in Brașov county Ligia Rodina, Maria Elena Cocuz A95 Clinical forms of Clostridium difficile colitis in children Gheorghiță Jugulete, Adina Stăncescu, Cristina Elena Popescu, Luminița Marin, Diana Zaharia, Cristina Dumitrescu, Endis Osman A96 Community-acquired pneumonia – demographic, clinical and etiological aspects Irina Niculescu, Augustin Cupșa, Iulian Diaconescu, Florentina Dumitrescu, Livia Dragonu, Andreea Stoian, Lucian Giubelan, Cristina Roskanovic A97 Acute myocarditis in an adult patient with chickenpox - Case report Ramona-Alexandra Zamfir, Mihaela Ionica, Otilia-Elisabeta Benea A98 Caustic oropharyngeal wound with acute group F streptococcal superinfection mimicking diphtheria – case report and differential diagnosis Maria-Cristina Sîrbu, AnaMaria Dobrotă, Alina Cristina Neguț, Roxana Duda, Rodica Bacruban, Daniela Pițigoi, Cristiana Cerasella Dragomirescu, Daniela Tălăpan, Olga Dorobăț, Adrian Streinu-Cercel, Anca Streinu-Cercel A99 Clostridium difficile infection in HIV-positive patients admitted in the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” in 2015 Mihaela Ionica, Ramona-Alexandra Zamfir, Alina Cozma, Otilia Elisabeta Benea A100 Title: Epidemiology of Candida oral infections (stomatitis) in Romania Sergiu Fendrihan, Ecaterina Scortan, Mircea Ioan Popa A101 Anthrax case series in south-eastern Romania Corneliu P Popescu, Șerban N Benea, Andra E Petcu, Adriana Hristea, Adrian Abagiu, Iuliana A Podea, Raluca E Jipa, Georgeta Ducu, Raluca M Hrișcă, Dragoș Florea, Manuela Nica, Eliza Manea, Simona Merișor, Cristian M Nicolae, Simin A Florescu, Irina M Dumitru, Emanoil Ceaușu, Sorin Rugină, Ruxandra V Moroti A102 Knowledge, risk perception and attitudes of healthcare workers at the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” regarding Ebola Daniela Pițigoi, Teodora Ionescu, Oana Săndulescu, Maria Nițescu, Bogdan Nițescu, Iulia Monica Mustaţă, Sorina Claudia Boldeanu, Florentina Furtunescu, Adrian Streinu-Cercel A103 A case of abdominopelvic actinomycosis with successful short-term antibiotic treatment Diana Gabriela Iacob, Simona Alexandra Iacob, Mihaela Gheorghe A104 A case of pneumonia caused by Raoultella planticola Iulian Diaconescu, Irina Niculescu, Floretina Dumitrescu, Lucian Giubelan A105 Vitamin D deficiency and sepsis in childhood Adriana Slavcovici, Raluca Tripon, Roxana Iubu, Cristian Marcu, Mihaela Sabou, Monica Muntean A106 The clinical and epidemiological aspects and prophylaxis of Lyme disease among patients who presented with tick bites to the Clinical Infectious Disease Hospital “Toma Ciorbă” Ion Chiriac, Tiberiu Holban, Liviu Tazlavanu A107 Drug-resistant tuberculosis in HIV infected patients Raluca Jipa, Eliza Manea, Roxana Cernat, Kezdi Iringo, Andrei Vâță, Manuela Arbune, Teodora Moisil, Adriana Hristea A108 Kidney injury molecule-1 and urinary tract infections Corina-Daniela Ene, Ilinca Nicolae, Roxana Simona Georgescu A109 The impact of microbiological agents on serum gangliosides in patients with benign prostate hyperplasia Corina-Daniela Ene, Cosmin-Victor Ene, Roxana Simona Georgescu, Marilena Ciortea , Lucreția Dulgheru, Ilinca Nicolae A110 Toxocariasis - the experience of the Iași Infectious Diseases Hospital between 2013–2015 Mihaela Cătălina Luca, Ioana-Alina Harja-Alexa, Roxana Nemescu, Mădălina Popazu, Andrei Ștefan Luca A111 Species of anaerobic Gram-positive cocci involved in odontogenic abscesses Gabriela Bancescu, Bogdan Dabu, Adrian Bancescu A112 Clostridium difficile infection recurrences Eliza Manea, Raluca Jipa, Adriana Hristea A113 Differential diagnosis of staphylococcal and tuberculous osteodiscitis – case report Adina Elena Ilie, Săftica-Mariana Pohrib, Alina Cristina Neguț, Maria-Sabina Tache, Maria Magdalena Moțoi, Oana Săndulescu, Ion Aurel Iliescu, Adrian Streinu-Cercel A114 Severe clinical forms of respiratory syncytial virus infections Cristina Tecu, Maria-Elena Mihai, Mihaela Lazăr, Carmen Cherciu, Alina Ivanciuc, Daniela Pițigoi, Emilia Lupulescu A115 Acinetobacter baumannii postoperative sepsis associated with Clostridium difficile enterocolitis in an immune suppressed elderly patient Mirela Paliu, Manuela Curescu, Bianca Cerbu, Iosif Marincu A116 Risk factors and their impact on psychopathology and quality of life among people living with HIV/AIDS in Romania Fulvia Ursoiu, Mirandolina Prișcă, George Ciprian Pribac A117 Antivirals susceptibility of influenza viruses circulating in Romania Maria Elena Mihai, Carmen Maria Cherciu, Alina Elena Ivanciuc, Cristina Tecu, Emilia Lupulescu A118 Retrospective study of hospitalized cases of sepsis at the Hospital Clinic of Infectious Diseases “Toma Ciorbă” Irina Bunescu, Tiberiu Holban, Ana Pasnin, Stela Semeniuc, Raisa Popovici, Galina Chiriacov",2016 Nov 1,"['Niculae, Cristian-Mihail', 'Manea, Eliza', 'Jipa, Raluca', 'Merisor, Simona', 'Moroti, Ruxandra', 'Benea, Serban', 'Hristea, Adriana', 'Neguț, Alina Cristina', 'Săndulescu, Oana', 'Streinu-Cercel, Anca', 'Mărculescu, Dana', 'Andrei, Magdalena Lorena', 'Ilie, Veronica', 'Popa, Marcela', 'Bleotu, Coralia', 'Chifiriuc, Carmen', 'Popa, Mircea Ioan', 'Streinu-Cercel, Adrian', 'Orfanu, Alina', 'Popescu, Cristina', 'Leuștean, Anca', 'Catană, Remulus', 'Negru, Anca', 'Badea, Alexandra', 'Orfanu, Radu', 'Tilișcan, Cătălin', 'Aramă, Victoria', 'Aramă, Ştefan Sorin', 'Vișan, Constanța-Angelica', 'Drăgănescu, Anca-Cristina', 'Bilașco, Anuța', 'Kouris, Camelia', 'Merișescu, Mădălina', 'Vasile, Magdalena', 'Slavu, Diana-Maria', 'Vintilă, Sabina', 'Osman, Endis', 'Oprea, Alina', 'Sandu, Sabina', 'Luminos, Monica', 'Orfanu, Alina', 'Aramă, Victoria', 'Aramă, Ştefan Sorin', 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Valentin', 'Cojuhari, Lilia', 'Jimbei, Paulina', 'Popescu, Cristina', 'Leuștean, Anca', 'Dragomirescu, Cristina', 'Orfanu, Alina', 'Murariu, Cristina', 'Stratan, Laurențiu', 'Badea, Alexandra', 'Tilișcan, Cătălin', 'Munteanu, Daniela', 'Năstase, Raluca', 'Molagic, Violeta', 'Rădulescu, Mihaela', 'Catană, Remulus', 'Aramă, Victoria', 'Popescu, Cristina', 'Stratan, Laurențiu', 'Catană, Remulus', 'Leuștean, Anca', 'Dragomirescu, Cristina', 'Badea, Alexandra', 'Murariu, Cristina', 'Năstase, Raluca', 'Molagic, Violeta', 'Munteanu, Daniela', 'Tilișcan, Cătălin', 'Rădulescu, Mihaela', 'Orfanu, Alina', 'Diaconu, Ioan', 'Negru, Anca', 'Bodosca, Iulia', 'Niță, Violeta', 'Aramă, Victoria', 'Leuștean, Anca', 'Aramă, Victoria', 'Orfanu, Alina', 'Catană, Remulus', 'Stratan, Laurențiu', 'Dragomirescu, Cristina', 'Murariu, Cristina', 'Badea, Alexandra', 'Tilișcan, Cătălin', 'Munteanu, Daniela', 'Molagic, Violeta', 'Năstase, Raluca', 'Rădulescu, Mihaela', 'Popescu, Cristina', 'Popescu, Cristina', 'Dragomirescu, Cristina', 'Leuștean, Anca', 'Murariu, Cristina', 'Stratan, Laurențiu', 'Badea, Alexandra', 'Catană, Remulus', 'Orfanu, Alina', 'Năstase, Raluca Mihaela', 'Molagic, Violeta', 'Munteanu, Daniela', 'Tilișcan, Cătălin', 'Aramă, Victoria', 'Aramă, Victoria', 'Catană, Remulus', 'Dragomirescu, Cristina', 'Murariu, Cristina', 'Leuștean, Anca', 'Stratan, Laurențiu', 'Badea, Alexandra', 'Orfanu, Alina', 'Negru, Anca', 'Năstase, Raluca', 'Molagic, Violeta', 'Munteanu, Daniela', 'Tilișcan, Cătălin', 'Rădulescu, Mihaela', 'Diaconu, Ioan', 'Niță, Violeta', 'Bodoșca, Iulia', 'Popescu, Cristina', 'Popescu, Cristina', 'Badea, Alexandra', 'Leuștean, Anca', 'Orfanu, Alina', 'Negru, Anca', 'Stratan, Laurențiu', 'Dragomirescu, Cristina', 'Catană, Remulus', 'Murariu, Cristina', 'Molagic, Violeta', 'Năstase, Raluca', 'Tilișcan, Cătălin', 'Munteanu, Daniela', 'Rădulescu, Mihaela', 'Diaconu, Ioan', 'Niță, Violeta', 'Bodoșca, Iulia', 'Aramă, Victoria', 'Popescu, Cristina', 'Orfanu, Alina', 'Leuștean, Anca', 'Badea, Alexandra', 'Stratan, Laurențiu', 'Catană, Remulus', 'Tilișcan, Cătălin', 'Aramă, Victoria', 'Popescu, Cristina', 'Murariu, Cristina', 'Dragomirescu, Cristina', 'Leuștean, Anca', 'Stratan, Laurențiu', 'Orfanu, Alina', 'Badea, Alexandra', 'Catană, Remulus', 'Negru, Anca', 'Tilișcan, Cătălin', 'Munteanu, Daniela', 'Rădulescu, Mihaela', 'Molagic, Violeta', 'Năstase, Raluca Mihaela', 'Diaconu, Ioan Alexandru', 'Bodoșca, Iulia', 'Niță, Violeta', 'Aramă, Victoria', 'Erturk, Yagmur', 'Săndulescu, Oana', 'Neguț, Alina Cristina', 'Șchiopu, Claudiu Mihai', 'Streinu-Cercel, Adrian', 'Streinu-Cercel, Anca', 'Molagic, Violeta', 'Tilișcan, Cătălin', 'Popescu, Cristina', 'Mihăilescu, Raluca', 'Munteanu, Daniela', 'Năstase, Raluca', 'Negru, Anca', 'Tenita, Angelica', 'Aramă, Victoria', 'Aramă, Ștefan Sorin', 'Iacob, Simona Alexandra', 'Iacob, Diana Gabriela', 'Luminos, Monica', 'Streinu-Cercel, Anca', 'Săndulescu, Oana', 'Predescu, Mioara', 'Mărdărescu, Alexandra', 'Tilișcan, Cătălin', 'Săndulescu, Mihai', 'Șchiopu, Claudiu Mihai', 'Streinu-Cercel, Adrian', 'Roșculeț, Cleo Nicoleta', 'Ciuca, Catrinel Olimpia', 'Toma, Dalila Ana', 'Apostolescu, Cătălin Gabriel', 'Rogoz, Andrei', 'Mitu, Cristina Elena', 'Stangaciu, Andrei', 'Mitescu, Viorica Daniela', 'Vladoiu, Tudor Gheorghe', 'Iovănescu, Doina Viorica', 'Săndulescu, Oana', 'Streinu-Cercel, Anca', 'Stoica, Monica Andreea', 'Preoțescu, Liliana Lucia', 'Manolache, Daniela', 'Ceapraga, Gabriela Jana', 'Moțoi, Maria Magdalena', 'Bradu, Luminița', 'Ilie, Adina', 'Mircea, Gabriela', 'Durbală, Ionel', 'Streinu-Cercel, Adrian', 'Russu, Irina', 'Holban, Tiberiu', 'Pantilimonov, Tatiana', 'Chiriacov, Galina', 'Macvovei, Arcadie', 'Scorohodico, Elena', 'Dmitriev, Oleg', 'Costache, Diana Alexandra', 'Benea, Anca', 'Manea, Eliza', 'Niculae, Cristian', 'Jipa, Raluca', 'Hristea, Adriana', 'Benea, Elisabeta', 'Moroti, Ruxandra', 'Benea, Șerban', 'Mitran, Mihai', 'Georgescu, Carmen', 'Mitran, Loredana', 'Vladareanu, Simona', 'Magirescu, Andreea Ioana', 'Andreev, Viorica', 'Nicolau, Cristina', 'Largu, Alexandra', 'Dorobat, Carmen', 'Manciuc, Carmen', 'Andreev, Viorica', 'Magirescu, Andreea Ioana', 'Isac, Ina', 'Nicolau, Cristina', 'Largu, Alexandra', 'Dorobat, Carmen', 'Manciuc, Carmen', 'Șerban, Iulia Gabriela', 'Resul, Ghiulendan', 'Marcaș, Consuela', 'Marincu, Iosif', 'Poptelecan, Patricia', 'Trincă, Bogdan', 'Mitrescu, Sorina', 'Tudor, Anca', 'Vlad, Daliborca', 'Tirnea, Livius', 'Baydaroglu, Nurcan', 'Neguț, Alina Cristina', 'Săndulescu, Oana', 'Manolache, Daniela', 'Ceapraga, Gabriela', 'Stoica, Monica Andreea', 'Streinu-Cercel, Anca', 'Streinu-Cercel, Adrian', 'Manciuc, Carmen', 'Pagute, Mariana', 'Nicolau, Cristina', 'Dorobăț, Carmen', 'Largu, Alexandra', 'Diaconu, Ioan-Alexandru', 'Stratan, Laurențiu', 'Ion, Daniela', 'Nichita, Luciana', 'Popescu, Cristina', 'Năstase, Raluca', 'Munteanu, Daniela', 'Molagic, Violeta', 'Tilișcan, Cătălin', 'Rădulescu, Mihaela', 'Diaconu, Alexandra', 'Negru, Anca', 'Orfanu, Alina', 'Dragomirescu, Cristina', 'Catană, Remulus', 'Leuștean, Anca', 'Duport-Dodot, Irina', 'Murariu, Cristina', 'Bodoșca, Iulia', 'Niță, Violeta', 'Badea, Alexandra', 'Aramă, Victoria', 'Mărdărescu, Mariana', 'Petre, Cristina', 'Iancu, Marieta', 'Ungurianu, Rodica', 'Cibea, Alina', 'Drăghicenoiu, Ruxandra', 'Tudor, Ana Maria', 'Vlad, Delia', 'Petrea, Sorin', 'Matei, Carina', 'Oțelea, Dan', 'Crăciun, Carmen', 'Anghelina, Cristian', 'Mărdărescu, Alexandra', 'Dumea, Elena', 'Streinu-Cercel, Adrian', 'Rugină, Sorin', 'Petcu, Lucian Cristian', 'Halichidis, Stela', 'Cambrea, Simona Claudia', 'Chiriac, Carmen', 'Bodnar, Nina-Ioana', 'Zaharia-Kezdi, Iringo-Erzsebet', 'Gîrbovan, Cristina', 'Incze, Andrea', 'Georgescu, Anca Meda', 'Iacob, Simona Alexandra', 'Iacob, Diana Gabriela', 'Panaitescu, Eugenia', 'Luminos, Monica', 'Cojocaru, Manole', 'Iacob, Simona Alexandra', 'Iacob, Diana Gabriela', 'Luminos, Monica', 'Laurențiu, Vochita', 'Andreia, Vochita', 'Radu, Opreanu', 'Bogdan, Trinca', 'Ovidiu, Rosca', 'Iosif, Marincu', 'Zamfir, Ramona', 'Angelescu, Alina', 'Popa, Alena Andreea', 'Jipa, Raluca', 'Moroti, Ruxandra', 'Hristea, Adriana', 'Gavriliu, Liana', 'Benea, Șerban', 'Benea, Elisabeta', 'Popa, Alena-Andreea', 'Ducu, Georgeta', 'Camburu, Daniela', 'Cozma, Alina', 'Podani, Manuela', 'Dumitriu, Roxana', 'Gavriliu, Liana', 'Benea, Șerban', 'Benea, Elisabeta', 'Stoian, Andreea Cristina', 'Dumitrescu, Florentina', 'Cupșa, Augustin', 'Giubelan, Lucian', 'Niculescu, Irina', 'Ionescu, Loredana', 'Dragonu, Livia', 'Abagiu, Adrian Octavian', 'Stoica, Loredana Nicoleta', 'Blaga, Catrinel', 'Koulosousas, Archontis', 'Ștefănescu, Roxana', 'Atomoaie, Alice', 'Paraschiv, Florentina', 'Duna, Florin Matache', 'Olteanu, Rodica', 'Ion, Roxana', 'Zota, Alexandra', 'Jaballah, Isra Ennour', 'Mahfoud, Lara', 'Preda, Georgeta', 'Constantin, Magda', 'Nicolae, Ilinca', 'Ene, Corina Daniela', 'Mitran, Mădălina Irina', 'Benea, Vasile', 'Tampa, Mircea', 'Georgescu, Simona Roxana', 'Bodoșca, Iulia Cristina', 'Murariu, Cristina', 'Tilișcan, Cătălin', 'Aramă, Victoria', 'Popescu, Cristina', 'Munteanu, Daniela', 'Rădulescu, Mihaela', 'Molagic, Violeta', 'Năstase, Raluca', 'Orfanu, Alina', 'Leuștean, Anca', 'Catană, Remulus', 'Negru, Anca', 'Streinu-Cercel, Adrian', 'Aramă, Sorin', 'Caramăngiu, Iuliana', 'Rosca, Ovidiu', 'Cialma, Monica', 'Opreanu, Radu', 'Vochita, Laurențiu', 'Marincu, Iosif', 'Murărescu, Vlad', 'Palaghiță, Marilena', 'Neguț, Alina Cristina', 'Camburu, Cornel', 'Streinu-Cercel, Adrian', 'Duşan, Irina', 'Poptelecan, Patricia', 'Trincă, Bogdan', 'Mitrescu, Sorina', 'Tirnea, Livius', 'Marincu, Iosif', 'Nicolescu, Narcisa', 'Crișan, Alexandru', 'Lăzureanu, Voichița', 'Laza, Ruxandra', 'Musta, Virgil', 'Marinescu, Adelina-Raluca', 'Bîrlad, Andreea', 'Miron, Victor Daniel', 'Drăgănescu, Anca Cristina', 'Vișan, Constanța-Angelica', 'Bilașco, Anuța', 'Pițigoi, Daniela', 'Săndulescu, Oana', 'Luminos, Monica Luminița', 'Luminos, Monica', 'Osman, Endis', 'Vasile, Magdalena', 'Drăgănescu, Anca Cristina', 'Vișan, Constanța-Angelica', 'Bilașco, Anuța', 'Kouris, Camelia', 'Șchiopu, Sabina', 'Merișescu, Mădălina', 'Luminos, Monica', 'Drăgănescu, Anca Cristina', 'Vișan, Constanța-Angelica', 'Bilașco, Anuța', 'Kouris, Camelia', 'Osman, Endis', 'Vintilă, Sabina', 'Vasile, Magda', 'Merișescu, Mădălina', 'Gavriliu, Liana Cătălina', 'Benea, Otilia Elisabeta', 'Angelescu, Alina', 'Zamfir, Ramona', 'Camburu, Daniela', 'Ducu, Georgeta', 'Cozma, Alina', 'Dumitriu, Roxana', 'Podani, Manuela', 'Benea, Șerban', 'Ionică, Mihaela', 'Jugulete, Gheorghiță', 'Stăncescu, Adina', 'Popescu, Cristina Elena', 'Marin, Luminița', 'Zaharia, Diana', 'Dumitrescu, Cristina', 'Tudor, Lucia', 'Vintilă, Sabina', 'Vișan, Constanța-Angelica', 'Drăgănescu, Anca Cristina', 'Bilașco, Anuța', 'Vasile, Magda', 'Merișescu, Mădălina', 'Kouris, Camelia', 'Negulescu, Cristina', 'Osman, Endis', 'Slavu, Diana-Maria', 'Vintilă, Sabina', 'Pițigoi, Daniela', 'Luminos, Monica', 'Caliman-Sturdza, Olga Adriana', 'Roșculeț, Cleo', 'Ciuca, Catrinel Olimpia', 'Toma, Dalila', 'Apostolescu, Cătălin', 'Rogoz, Andrei', 'Stangaciu, Andrei', 'Mitescu, Viorica', 'Iovănescu, Doina', 'Camburu, Cornel', 'Manu, Bogdana', 'Vaduva-Enoiu, Ana', 'Stanculete, Ramona Georgiana', 'Marinescu, Adelina Raluca', 'Lazureanu, Voichita Elena', 'Niță, Elena-Violeta', 'Dumitru, Sînziana', 'Munteanu, Daniela-Ioana', 'Negru, Anca Ruxandra', 'Catană, Remulus', 'Diaconu, Ioan', 'Manu, Bogdana', 'Ionescu, Ligia', 'Ion, Liliana', 'Tilișcan, Cătălin', 'Aramă, Victoria', 'Iovănescu, Doina Viorica', 'Roșculeț, Cleo Nicoleta', 'Rogoz, Andrei', 'Apostolescu, Cătălin', 'Mitescu, Viorica', 'Vladoiu, Tudor', 'Toma, Dalila', 'Ciuca, Catrinel', 'Șerban, Iulia Gabriela', 'Neacșu, Marioara', 'Georgescu, Simona Roxana', 'Benea, Vasile', 'Ene, Corina Daniela', 'Tampa, Mircea', 'Mitran, Cristina Iulia', 'Nicolae, Ilinca', 'Pribac, George Ciprian', 'Prisca, Mirandolina', 'Ursoiu, Fulvia', 'Neamtu, Carmen', 'Totolici, Bogdan', 'Cotoraci, Coralia', 'Ardelean, Aurel', 'Albu, Simona Elena', 'Carsote, Mara', 'Miclăuș, Beatrice', 'Mihai, Diana', 'Săndulescu, Oana', 'Vasiliu, Cristina', 'Vasiliu, Cristina', 'Carsote, Mara', 'Gorgoi, Corina', 'Miclăuș, Beatrice', 'Mihai, Diana', 'Săndulescu, Oana', 'Albu, Simona Elena', 'Blescun, Amelia', 'Breaza, Gelu', 'Vintila, Sabina', 'Mihai, Felicia', 'Omer, Meilin', 'Dragan, Cornel', 'Pitigoi, Daniela', 'Ciucu, Mirela', 'Ionescu, Marius-Dan', 'Roskanovic, Cristina', 'Barbu, Valentina', 'Diaconescu, Iulian', 'Dumitrescu, Florentina', 'Niculescu, Irina', 'Ionică, Mihaela', 'Zamfir, Ramona-Alexandra', 'Cozma, Alina', 'Benea, Otilia Elisabeta', 'Dumitru, Alexandra-Sînziana', 'Munteanu, Daniela-Ioana', 'Niță, Violeta', 'Popescu, Cristina', 'Bodosca, Iulia', 'Tenita, Angelica', 'Ispas, Viorica', 'Aramă, Victoria', 'Benea, Vasile', 'Georgescu, Simona Roxana', 'Tampa, Mircea', 'Leahu, Diana Oana', 'Safta, Cristina Maria', 'Benea, Mihaela Anca', 'Săndulescu, Oana', 'Munteanu, Octavian', 'Bohâlțea, Roxana', 'Trașcă, Livia', 'Cîrstoiu, Monica', 'Iovănescu, Doina Viorica', 'Roșculeț, Cleo Nicoleta', 'Rogoz, Andrei', 'Apostolescu, Cătălin Gabriel', 'Mitescu, Viorica Daniela', 'Vladoiu, Tudor Gheorghe', 'Toma, Dalila', 'Ciuca, Catrinel', 'Georgescu, Mădălina', 'Pițigoi, Daniela', 'Ivanciuc, Alina Elena', 'Lazar, Mihaela', 'Ionescu, Teodora', 'Cherciu, Carmen Maria', 'Țecu, Cristina', 'Mihai, Maria Elena', 'Nițescu, Maria', 'Bacruban, Rodica', 'Azamfire, Delia', 'Dumitrescu, Aura', 'Ianosik, Elena', 'Leca, Daniela', 'Duca, Elena', 'Teodor, Andra', 'Bejan, Codrina', 'Ceaușu, Emanoil', 'Florescu, Simin-Aysel', 'Popescu, Corneliu', 'Târdei, Grațiela', 'Juganariu, Codrina', 'Lupulescu, Emilia', 'Rodina, Ligia', 'Cocuz, Maria Elena', 'Jugulete, Gheorghiță', 'Stăncescu, Adina', 'Popescu, Cristina Elena', 'Marin, Luminița', 'Zaharia, Diana', 'Dumitrescu, Cristina', 'Osman, Endis', 'Niculescu, Irina', 'Cupșa, Augustin', 'Diaconescu, Iulian', 'Dumitrescu, Florentina', 'Dragonu, Livia', 'Stoian, Andreea', 'Giubelan, Lucian', 'Roskanovic, Cristina', 'Zamfir, Ramona-Alexandra', 'Ionica, Mihaela', 'Benea, Otilia-Elisabeta', 'Sîrbu, Maria-Cristina', 'Dobrotă, AnaMaria', 'Neguț, Alina Cristina', 'Duda, Roxana', 'Bacruban, Rodica', 'Pițigoi, Daniela', 'Dragomirescu, Cristiana Cerasella', 'Tălăpan, Daniela', 'Dorobăț, Olga', 'Streinu-Cercel, Adrian', 'Streinu-Cercel, Anca', 'Ionica, Mihaela', 'Zamfir, Ramona-Alexandra', 'Cozma, Alina', 'Benea, Otilia Elisabeta', 'Fendrihan, Sergiu', 'Scortan, Ecaterina', 'Popa, Mircea Ioan', 'Popescu, Corneliu P.', 'Benea, Șerban N.', 'Petcu, Andra E.', 'Hristea, Adriana', 'Abagiu, Adrian', 'Podea, Iuliana A.', 'Jipa, Raluca E.', 'Ducu, Georgeta', 'Hrișcă, Raluca M.', 'Florea, Dragoș', 'Nica, Manuela', 'Manea, Eliza', 'Merișor, Simona', 'Nicolae, Cristian M.', 'Florescu, Simin A.', 'Dumitru, Irina M.', 'Ceaușu, Emanoil', 'Rugină, Sorin', 'Moroti, Ruxandra V.', 'Pițigoi, Daniela', 'Ionescu, Teodora', 'Săndulescu, Oana', 'Nițescu, Maria', 'Nițescu, Bogdan', 'Mustaţă, Iulia Monica', 'Boldeanu, Sorina Claudia', 'Furtunescu, Florentina', 'Streinu-Cercel, Adrian', 'Iacob, Diana Gabriela', 'Iacob, Simona Alexandra', 'Gheorghe, Mihaela', 'Slavcovici, Adriana', 'Tripon, Raluca', 'Iubu, Roxana', 'Marcu, Cristian', 'Sabou, Mihaela', 'Muntean, Monica', 'Chiriac, Ion', 'Holban, Tiberiu', 'Tazlavanu, Liviu', 'Jipa, Raluca', 'Manea, Eliza', 'Cernat, Roxana', 'Iringo, Kezdi', 'Vâță, Andrei', 'Arbune, Manuela', 'Moisil, Teodora', 'Hristea, Adriana', 'Ene, Corina-Daniela', 'Nicolae, Ilinca', 'Georgescu, Roxana Simona', 'Ene, Corina-Daniela', 'Ene, Cosmin-Victor', 'Georgescu, Roxana Simona', 'Ciortea, Marilena', 'Dulgheru, Lucreția', 'Nicolae, Ilinca', 'Luca, Mihaela Cătălina', 'Harja-Alexa, Ioana-Alina', 'Nemescu, Roxana', 'Popazu, Mădălina', 'Luca, Andrei Ștefan', 'Bancescu, Gabriela', 'Dabu, Bogdan', 'Bancescu, Adrian', 'Manea, Eliza', 'Jipa, Raluca', 'Hristea, Adriana', 'Ilie, Adina Elena', 'Pohrib, Săftica-Mariana', 'Neguț, Alina Cristina', 'Tache, Maria-Sabina', 'Moțoi, Maria Magdalena', 'Săndulescu, Oana', 'Iliescu, Ion Aurel', 'Streinu-Cercel, Adrian', 'Tecu, Cristina', 'Mihai, Maria-Elena', 'Lazăr, Mihaela', 'Cherciu, Carmen', 'Ivanciuc, Alina', 'Pițigoi, Daniela', 'Lupulescu, Emilia', 'Paliu, Mirela', 'Curescu, Manuela', 'Cerbu, Bianca', 'Marincu, Iosif', 'Mihai, Maria Elena', 'Cherciu, Carmen Maria', 'Ivanciuc, Alina Elena', 'Tecu, Cristina', 'Lupulescu, Emilia', 'Bunescu, Irina', 'Holban, Tiberiu', 'Pasnin, Ana', 'Semeniuc, Stela', 'Popovici, Raisa', 'Chiriacov, Galina']",BMC Infect Dis,,,True
a09daa4101801d9b65bcc053116505b0022e0640,PMC,Planning horizon affects prophylactic decision-making and epidemic dynamics,http://dx.doi.org/10.7717/peerj.2678,PMC5103819,27843714,CC BY,"The spread of infectious diseases can be impacted by human behavior, and behavioral decisions often depend implicitly on a planning horizon—the time in the future over which options are weighed. We investigate the effects of planning horizons on epidemic dynamics. We developed an epidemiological agent-based model (along with an ODE analog) to explore the decision-making of self-interested individuals on adopting prophylactic behavior. The decision-making process incorporates prophylaxis efficacy and disease prevalence with the individuals’ payoffs and planning horizon. Our results show that for short and long planning horizons individuals do not consider engaging in prophylactic behavior. In contrast, individuals adopt prophylactic behavior when considering intermediate planning horizons. Such adoption, however, is not always monotonically associated with the prevalence of the disease, depending on the perceived protection efficacy and the disease parameters. Adoption of prophylactic behavior reduces the epidemic peak size while prolonging the epidemic and potentially generates secondary waves of infection. These effects can be made stronger by increasing the behavioral decision frequency or distorting an individual’s perceived risk of infection.",2016 Nov 8,"['Nardin, Luis G.', 'Miller, Craig R.', 'Ridenhour, Benjamin J.', 'Krone, Stephen M.', 'Joyce, Paul', 'Baumgaertner, Bert O.']",PeerJ,,,False
352fc70d79c0668a5a7583538fe0167c1fd785d1,PMC,Bats and Academics: How Do Scientists Perceive Their Object of Study?,http://dx.doi.org/10.1371/journal.pone.0165969,PMC5104368,27832185,CC BY,"Bats are associated with conflicting perceptions among humans, ranging from affection to disgust. If these attitudes can be associated with various factors among the general public (e.g. social norms, lack of knowledge), it is also important to understand the attitude of scientists who study bats. Such reflexive information on the researchers community itself could indeed help designing adequate mixed communication tools aimed at protecting bats and their ecosystems, as well as humans living in their vicinity that could be exposed to their pathogens. Thus, we conducted an online survey targeting researchers who spend a part of their research activity studying bats. Our aim was to determine (1) how they perceive their object of study, (2) how they perceive the representation of bats in the media and by the general population, (3) how they protect themselves against pathogen infections during their research practices, and (4) their perceptions of the causes underlying the decline in bat populations worldwide. From the 587 completed responses (response rate of 28%) having a worldwide distribution, the heterogeneity of the scientists’ perception of their own object of study was highlighted. In the majority of cases, this depended on the type of research they conducted (i.e. laboratory versus field studies) as well as their research speciality. Our study revealed a high level of personal protection equipment being utilised against pathogens during scientific practices, although the role bats play as reservoirs for a number of emerging pathogens remains poorly known. Our results also disclosed the unanimity among specialists in attributing a direct role for humans in the global decline of bat populations, mainly via environmental change, deforestation, and agriculture intensification. Overall, the present study suggests the need for better communication regarding bats and their biology, their role within the scientific community, as well as in the general public population. As a consequence, increased knowledge regarding scientists’ perceptions of bats should improve the role scientists play in influencing the perception of bats by the general public.",2016 Nov 10,"['Boëte, Christophe', 'Morand, Serge']",PLoS One,,,True
add093424f4f1c1da746abb3227193fb2fefbefa,PMC,Viral Evasion Strategies in Type I IFN Signaling – A Summary of Recent Developments,http://dx.doi.org/10.3389/fimmu.2016.00498,PMC5104748,27891131,CC BY,"The immune system protects the organism against infections and the damage associated with them. The first line of defense against pathogens is the innate immune response. In the case of a viral infection, it induces the interferon (IFN) signaling cascade and eventually the expression of type I IFN, which then causes an antiviral state in the cells. However, many viruses have developed strategies to counteract this mechanism and prevent the production of IFN. In order to modulate or inhibit the IFN signaling cascade in their favor, viruses have found ways to interfere at every single step of the cascade, for example, by inducing protein degradation or cleavage, or by mediate protein polyubiquitination. In this article, we will review examples of viruses that modulate the IFN response and describe the mechanisms they use.",2016 Nov 11,"['Schulz, Katharina S.', 'Mossman, Karen L.']",Front Immunol,,,True
1146cc4ce6094ad35cc188166285b8c519986b6d,PMC,Complete Genome Sequences of Porcine Epidemic Diarrhea Virus Strains JSLS-1/2015 and JS-2/2015 Isolated from China,http://dx.doi.org/10.1128/genomeA.01200-16,PMC5105090,27834697,CC BY,"Two porcine epidemic diarrhea virus (PEDV) strains, JSLS-1/2015 and JS-2/2015, were isolated from piglets with watery diarrhea in South China. Two genomic sequences were highly homologous to the attenuated DR13 strain. Furthermore, JSLS-1/2015 contains a 24-amino-acid deletion in open reading frame 1b, which was first reported in PEDV isolates.",2016 Nov 10,"['Tao, Jie', 'Li, Benqiang', 'Zhang, Chunling', 'Liu, Huili']",Genome Announc,,,True
c36f5134f23a74677ed9d3a39f2eb8b4b19ad6e5,PMC,Complete Genome Sequence of Human Coronavirus OC43 Isolated from Mexico,http://dx.doi.org/10.1128/genomeA.01256-16,PMC5105101,27834708,CC BY,"We report the complete genome sequence of the first Mexican human coronavirus (HCoV) OC43, obtained by new-generation sequencing and a metagenomic approach, isolated from a child hospitalized with pneumonia. The genome is closely related to the other OC43 genome sequences available, ranging from 99.8% to 98.2% nucleotide sequence identity.",2016 Nov 10,"['Taboada, B. T.', 'Isa, P.', 'Espinoza, M. A.', 'Aponte, F. E.', 'Arias-Ortiz, M. A.', 'Monge-Martínez, J.', 'Rodríguez-Vázquez, R.', 'Díaz-Hernández, F.', 'Zárate-Vidal, F.', 'Wong-Chew, R. M.', 'Firo-Reyes, V.', 'del Río-Almendárez, C. N.', 'Gaitán-Meza, J.', 'Villaseñor-Sierra, A.', 'Martínez-Aguilar, G.', 'García-Borjas, M.', 'Noyola, D. E.', 'Pérez-Gónzalez, L. F.', 'López, S.', 'Santos-Preciado, J. I.', 'Arias, C. F.']",Genome Announc,,,True
2e313159ccde7f6fbd8d036a04beb2ce3a2809e4,PMC,Detection of a novel circovirus PCV3 in pigs with cardiac and multi-systemic inflammation,http://dx.doi.org/10.1186/s12985-016-0642-z,PMC5105309,27835942,CC BY,"BACKGROUND: Porcine circovirus 2 causes different clinical syndromes resulting in a significant economic loss in the pork industry. Three pigs with unexplained cardiac and multi-organ inflammation that tested negative for PCV2 and other known porcine pathogens were further analyzed. METHODS: Histology was used to identify microscopic lesions in multiple tissues. Metagenomics was used to detect viral sequences in tissue homogenates. In situ hybridization was used to detect viral RNA expression in cardiac tissue. RESULTS: In all three cases we characterized the genome of a new circovirus we called PCV3 with a replicase and capsid proteins showing 55 and 35 % identities to the genetically-closest proteins from a bat-feces associated circovirus and were even more distant to those of porcine circovirus 1 and 2. Common microscopic lesions included non-suppurative myocarditis and/or cardiac arteriolitis. Viral mRNA was detected intralesionally in cardiac cells. Deep sequencing in tissues also revealed the presence of porcine astrovirus 4 in all three animals as well as rotavirus A, porcine cytomegalovirus and porcine hemagglutinating encephalomyelitis virus in individual cases. CONCLUSION: The pathogenicity and molecular epidemiology of this new circovirus, alone or in the context of co-infections, warrants further investigations.",2016 Nov 11,"['Phan, Tung Gia', 'Giannitti, Federico', 'Rossow, Stephanie', 'Marthaler, Douglas', 'Knutson, Todd', 'Li, Linlin', 'Deng, Xutao', 'Resende, Talita', 'Vannucci, Fabio', 'Delwart, Eric']",Virol J,,,True
79b67a52cb7757c9fae9636913c30b5ee39e68af,PMC,"Chikungunya virus infectivity, RNA replication and non-structural polyprotein processing depend on the nsP2 protease’s active site cysteine residue",http://dx.doi.org/10.1038/srep37124,PMC5109220,27845418,CC BY,"Chikungunya virus (CHIKV), genus Alphavirus, family Togaviridae, has a positive-stand RNA genome approximately 12 kb in length. In infected cells, the genome is translated into non-structural polyprotein P1234, an inactive precursor of the viral replicase, which is activated by cleavages carried out by the non-structural protease, nsP2. We have characterized CHIKV nsP2 using both cell-free and cell-based assays. First, we show that Cys478 residue in the active site of CHIKV nsP2 is indispensable for P1234 processing. Second, the substrate requirements of CHIKV nsP2 are quite similar to those of nsP2 of related Semliki Forest virus (SFV). Third, substitution of Ser482 residue, recently reported to contribute to the protease activity of nsP2, with Ala has almost no negative effect on the protease activity of CHIKV nsP2. Fourth, Cys478 to Ala as well as Trp479 to Ala mutations in nsP2 completely abolished RNA replication in CHIKV and SFV trans-replication systems. In contrast, trans-replicases with Ser482 to Ala mutation were similar to wild type counterparts. Fifth, Cys478 to Ala as well as Trp479 to Ala mutations in nsP2 abolished the rescue of infectious virus from CHIKV RNA transcripts while Ser482 to Ala mutation had no effect. Thus, CHIKV nsP2 is a cysteine protease.",2016 Nov 15,"['Rausalu, Kai', 'Utt, Age', 'Quirin, Tania', 'Varghese, Finny S.', 'Žusinaite, Eva', 'Das, Pratyush Kumar', 'Ahola, Tero', 'Merits, Andres']",Sci Rep,,,True
2f0190b3d09170b52a39967ada3c55f972543d3e,PMC,"Chikungunya virus infectivity, RNA replication and non-structural polyprotein processing depend on the nsP2 protease’s active site cysteine residue",http://dx.doi.org/10.1038/srep37124,PMC5109220,27845418,CC BY,"Chikungunya virus (CHIKV), genus Alphavirus, family Togaviridae, has a positive-stand RNA genome approximately 12 kb in length. In infected cells, the genome is translated into non-structural polyprotein P1234, an inactive precursor of the viral replicase, which is activated by cleavages carried out by the non-structural protease, nsP2. We have characterized CHIKV nsP2 using both cell-free and cell-based assays. First, we show that Cys478 residue in the active site of CHIKV nsP2 is indispensable for P1234 processing. Second, the substrate requirements of CHIKV nsP2 are quite similar to those of nsP2 of related Semliki Forest virus (SFV). Third, substitution of Ser482 residue, recently reported to contribute to the protease activity of nsP2, with Ala has almost no negative effect on the protease activity of CHIKV nsP2. Fourth, Cys478 to Ala as well as Trp479 to Ala mutations in nsP2 completely abolished RNA replication in CHIKV and SFV trans-replication systems. In contrast, trans-replicases with Ser482 to Ala mutation were similar to wild type counterparts. Fifth, Cys478 to Ala as well as Trp479 to Ala mutations in nsP2 abolished the rescue of infectious virus from CHIKV RNA transcripts while Ser482 to Ala mutation had no effect. Thus, CHIKV nsP2 is a cysteine protease.",2016 Nov 15,"['Rausalu, Kai', 'Utt, Age', 'Quirin, Tania', 'Varghese, Finny S.', 'Žusinaite, Eva', 'Das, Pratyush Kumar', 'Ahola, Tero', 'Merits, Andres']",Sci Rep,,,False
fe90da34ca7b4f7fd6711bd870cb2163b8fd4ef4,PMC,Microbiome analysis reveals the abundance of bacterial pathogens in Rousettus leschenaultii guano,http://dx.doi.org/10.1038/srep36948,PMC5109407,27845426,CC BY,"Bats are crucial for proper functioning of an ecosystem. They provide various important services to ecosystem and environment. While, bats are well-known carrier of pathogenic viruses, their possible role as a potential carrier of pathogenic bacteria is under-explored. Here, using culture-based approach, employing multiple bacteriological media, over thousand bacteria were cultivated and identified from Rousettus leschenaultii (a frugivorous bat species), the majority of which were from the family Enterobacteriaceae and putative pathogens. Next, pathogenic potential of most frequently cultivated component of microbiome i.e. Escherichia coli was assessed to identify its known pathotypes which revealed the presence of virulent factors in many cultivated E. coli isolates. Applying in-depth bacterial community analysis using high-throughput 16 S rRNA gene sequencing, a high inter-individual variation was observed among the studied guano samples. Interestingly, a higher diversity of bacterial communities was observed in decaying guano representative. The search against human pathogenic bacteria database at 97% identity, a small proportion of sequences were found associated to well-known human pathogens. The present study thus indicates that this bat species may carry potential bacterial pathogens and advice to study the effect of these pathogens on bats itself and the probable mode of transmission to humans and other animals.",2016 Nov 15,"['Banskar, Sunil', 'Bhute, Shrikant S.', 'Suryavanshi, Mangesh V.', 'Punekar, Sachin', 'Shouche, Yogesh S.']",Sci Rep,,,True
85b681d7b41efe21e90c9fa10f67508ef7aea537,PMC,Microbiome analysis reveals the abundance of bacterial pathogens in Rousettus leschenaultii guano,http://dx.doi.org/10.1038/srep36948,PMC5109407,27845426,CC BY,"Bats are crucial for proper functioning of an ecosystem. They provide various important services to ecosystem and environment. While, bats are well-known carrier of pathogenic viruses, their possible role as a potential carrier of pathogenic bacteria is under-explored. Here, using culture-based approach, employing multiple bacteriological media, over thousand bacteria were cultivated and identified from Rousettus leschenaultii (a frugivorous bat species), the majority of which were from the family Enterobacteriaceae and putative pathogens. Next, pathogenic potential of most frequently cultivated component of microbiome i.e. Escherichia coli was assessed to identify its known pathotypes which revealed the presence of virulent factors in many cultivated E. coli isolates. Applying in-depth bacterial community analysis using high-throughput 16 S rRNA gene sequencing, a high inter-individual variation was observed among the studied guano samples. Interestingly, a higher diversity of bacterial communities was observed in decaying guano representative. The search against human pathogenic bacteria database at 97% identity, a small proportion of sequences were found associated to well-known human pathogens. The present study thus indicates that this bat species may carry potential bacterial pathogens and advice to study the effect of these pathogens on bats itself and the probable mode of transmission to humans and other animals.",2016 Nov 15,"['Banskar, Sunil', 'Bhute, Shrikant S.', 'Suryavanshi, Mangesh V.', 'Punekar, Sachin', 'Shouche, Yogesh S.']",Sci Rep,,,False
41acbf6dfc7569490c731f87cf3e629fc0c65b42,PMC,Microbiome analysis reveals the abundance of bacterial pathogens in Rousettus leschenaultii guano,http://dx.doi.org/10.1038/srep36948,PMC5109407,27845426,CC BY,"Bats are crucial for proper functioning of an ecosystem. They provide various important services to ecosystem and environment. While, bats are well-known carrier of pathogenic viruses, their possible role as a potential carrier of pathogenic bacteria is under-explored. Here, using culture-based approach, employing multiple bacteriological media, over thousand bacteria were cultivated and identified from Rousettus leschenaultii (a frugivorous bat species), the majority of which were from the family Enterobacteriaceae and putative pathogens. Next, pathogenic potential of most frequently cultivated component of microbiome i.e. Escherichia coli was assessed to identify its known pathotypes which revealed the presence of virulent factors in many cultivated E. coli isolates. Applying in-depth bacterial community analysis using high-throughput 16 S rRNA gene sequencing, a high inter-individual variation was observed among the studied guano samples. Interestingly, a higher diversity of bacterial communities was observed in decaying guano representative. The search against human pathogenic bacteria database at 97% identity, a small proportion of sequences were found associated to well-known human pathogens. The present study thus indicates that this bat species may carry potential bacterial pathogens and advice to study the effect of these pathogens on bats itself and the probable mode of transmission to humans and other animals.",2016 Nov 15,"['Banskar, Sunil', 'Bhute, Shrikant S.', 'Suryavanshi, Mangesh V.', 'Punekar, Sachin', 'Shouche, Yogesh S.']",Sci Rep,,,False
475d515546fd58bf9e9d43e9fa938817f797824a,PMC,Recalibrating disease parameters for increasing realism in modeling epidemics in closed settings,http://dx.doi.org/10.1186/s12879-016-2003-3,PMC5109722,27842507,CC BY,"BACKGROUND: The homogeneous mixing assumption is widely adopted in epidemic modelling for its parsimony and represents the building block of more complex approaches, including very detailed agent-based models. The latter assume homogeneous mixing within schools, workplaces and households, mostly for the lack of detailed information on human contact behaviour within these settings. The recent data availability on high-resolution face-to-face interactions makes it now possible to assess the goodness of this simplified scheme in reproducing relevant aspects of the infection dynamics. METHODS: We consider empirical contact networks gathered in different contexts, as well as synthetic data obtained through realistic models of contacts in structured populations. We perform stochastic spreading simulations on these contact networks and in populations of the same size under a homogeneous mixing hypothesis. We adjust the epidemiological parameters of the latter in order to fit the prevalence curve of the contact epidemic model. We quantify the agreement by comparing epidemic peak times, peak values, and epidemic sizes. RESULTS: Good approximations of the peak times and peak values are obtained with the homogeneous mixing approach, with a median relative difference smaller than 20 % in all cases investigated. Accuracy in reproducing the peak time depends on the setting under study, while for the peak value it is independent of the setting. Recalibration is found to be linear in the epidemic parameters used in the contact data simulations, showing changes across empirical settings but robustness across groups and population sizes. CONCLUSIONS: An adequate rescaling of the epidemiological parameters can yield a good agreement between the epidemic curves obtained with a real contact network and a homogeneous mixing approach in a population of the same size. The use of such recalibrated homogeneous mixing approximations would enhance the accuracy and realism of agent-based simulations and limit the intrinsic biases of the homogeneous mixing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-2003-3) contains supplementary material, which is available to authorized users.",2016 Nov 14,"['Bioglio, Livio', 'Génois, Mathieu', 'Vestergaard, Christian L.', 'Poletto, Chiara', 'Barrat, Alain', 'Colizza, Vittoria']",BMC Infect Dis,,,False
82e33ea1413ab8560304175a8281348a156c2e47,PMC,Recalibrating disease parameters for increasing realism in modeling epidemics in closed settings,http://dx.doi.org/10.1186/s12879-016-2003-3,PMC5109722,27842507,CC BY,"BACKGROUND: The homogeneous mixing assumption is widely adopted in epidemic modelling for its parsimony and represents the building block of more complex approaches, including very detailed agent-based models. The latter assume homogeneous mixing within schools, workplaces and households, mostly for the lack of detailed information on human contact behaviour within these settings. The recent data availability on high-resolution face-to-face interactions makes it now possible to assess the goodness of this simplified scheme in reproducing relevant aspects of the infection dynamics. METHODS: We consider empirical contact networks gathered in different contexts, as well as synthetic data obtained through realistic models of contacts in structured populations. We perform stochastic spreading simulations on these contact networks and in populations of the same size under a homogeneous mixing hypothesis. We adjust the epidemiological parameters of the latter in order to fit the prevalence curve of the contact epidemic model. We quantify the agreement by comparing epidemic peak times, peak values, and epidemic sizes. RESULTS: Good approximations of the peak times and peak values are obtained with the homogeneous mixing approach, with a median relative difference smaller than 20 % in all cases investigated. Accuracy in reproducing the peak time depends on the setting under study, while for the peak value it is independent of the setting. Recalibration is found to be linear in the epidemic parameters used in the contact data simulations, showing changes across empirical settings but robustness across groups and population sizes. CONCLUSIONS: An adequate rescaling of the epidemiological parameters can yield a good agreement between the epidemic curves obtained with a real contact network and a homogeneous mixing approach in a population of the same size. The use of such recalibrated homogeneous mixing approximations would enhance the accuracy and realism of agent-based simulations and limit the intrinsic biases of the homogeneous mixing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-2003-3) contains supplementary material, which is available to authorized users.",2016 Nov 14,"['Bioglio, Livio', 'Génois, Mathieu', 'Vestergaard, Christian L.', 'Poletto, Chiara', 'Barrat, Alain', 'Colizza, Vittoria']",BMC Infect Dis,,,True
642e03f3b71051b01c77af78f51bb4ef5d00ad08,PMC,Fatal Community-acquired Pneumonia in Children Caused by Re-emergent Human Adenovirus 7d Associated with Higher Severity of Illness and Fatality Rate,http://dx.doi.org/10.1038/srep37216,PMC5110970,27848998,CC BY,"Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), such as community-acquired pneumonia. HAdV-7d, a re-emergent genomic variant, has been recently reported in Asia and the United States after a several-decade absence. However, whether HAdV-7d is associated with higher severity than other types is currently unclear. In this study, the clinical and epidemiological investigation showed that fever, cough, and sore throat were the three most common respiratory symptoms of HAdV infections. HAdV-7 caused longer duration of fever, higher morbidity of tachypnea/dyspnea, pleural effusion, diarrhea, hepatosplenomegaly, consciousness alteration, as well as higher rates of pneumonia, mechanical ventilation and higher fatality rate (28.6%) than other types, particularly HAdV-3 and HAdV-2. The genomes of seven HAdV-7d isolates from mild, severe, and fatal cases were sequenced and highly similar with each other. Surprisingly, two isolates (2011, 2012) had 100% identical genomes with an earlier strain from a fatal ARD outbreak in China (2009), which elucidates the virus origin and confirms the unexpected HAdV genomic conservation and stability. Phylogenetic analysis indicated that L1 52/55-kDa DNA packaging protein may be associated with the higher severity of illness and fatality rate of HAdV-7. Clinicians need to be aware of HAdVs in children with ARD.",2016 Nov 16,"['Yu, Zhiwu', 'Zeng, Zhiwei', 'Zhang, Jing', 'Pan, Yuxian', 'Chen, Manjun', 'Guo, Yonghui', 'Yu, Nan', 'Chodosh, James', 'Fu, Ning', 'Che, Xiaoyan', 'Zhang, Qiwei']",Sci Rep,,,True
a34b4ae8ac728d948a40b4c6f0d825b319d88ad7,PMC,Coevolution of paired receptors in Xenopus carcinoembryonic antigen-related cell adhesion molecule families suggests appropriation as pathogen receptors,http://dx.doi.org/10.1186/s12864-016-3279-9,PMC5112662,27852220,CC BY,"BACKGROUND: In mammals, CEACAM1 and closely related members represent paired receptors with similar extracellular ligand-binding regions and cytoplasmic domains with opposing functions. Human CEACAM1 and CEACAM3 which have inhibitory ITIM/ITSM and activating ITAM-like motifs, respectively, in their cytoplasmic regions are such paired receptors. Various bacterial pathogens bind to CEACAM1 on epithelial and immune cells facilitating both entry into the host and down-regulation of the immune response whereas interaction with granulocyte-specific CEACAM3 leads to their uptake and destruction. It is unclear whether paired CEACAM receptors also exist in other vertebrate clades. RESULTS: We identified more than 80 ceacam genes in Xenopus tropicalis and X. laevis. They consist of two subgroups containing one or two putative paired receptor pairs each. Analysis of genomic sequences of paired receptors provide evidence that their highly similar ligand binding domains were adjusted by recent gene conversion events. In contrast, selection for diversification is observed among inhibitory receptor orthologs of the two frogs which split some 60 million years ago. The allotetraploid X. laevis arose later by hybridization of two closely related species. Interestingly, despite the conservation of the genomic landscape surrounding the homeologous ceacam loci only one locus resembles the one found in X. tropicalis. From the second X. laevis locus more than 80 % of the ceacam genes were lost including 5 of the 6 paired receptor genes. This suggests that once the gene for one of the paired receptors is lost the remaining gene cluster degrades rapidly probably due to lack of selection pressure exerted by pathogens. CONCLUSIONS: The presence of paired receptors and selection for diversification suggests that also in amphibians CEACAM1-related inhibitory proteins are or were used as pathogen receptors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3279-9) contains supplementary material, which is available to authorized users.",2016 Nov 16,"['Zimmermann, Wolfgang', 'Kammerer, Robert']",BMC Genomics,,,True
281520c659ef5b7b5561307d5a91a00526e994f3,PMC,Viral-bacterial coinfection affects the presentation and alters the prognosis of severe community-acquired pneumonia,http://dx.doi.org/10.1186/s13054-016-1517-9,PMC5112669,27852281,CC BY,"BACKGROUND: Multiplex polymerase chain reaction (mPCR) enables recovery of viruses from airways of patients with community-acquired pneumonia (CAP), although their clinical impact remains uncertain. METHODS: Among consecutive adult patients who had undergone a mPCR within 72 hours following their admission to one intensive care unit (ICU), we retrospectively included those with a final diagnosis of CAP. Four etiology groups were clustered: bacterial, viral, mixed (viral-bacterial) and no etiology. A composite criterion of complicated course (hospital death or mechanical ventilation > 7 days) was used. A subgroup analysis compared patients with bacterial and viral-bacterial CAP matched on the bacterial pathogens. RESULTS: Among 174 patients (132 men [76 %], age 63 [53–75] years, SAPSII 38 [27;55], median PSI score 106 [78;130]), bacterial, viral, mixed and no etiology groups gathered 46 (26 %), 53 (31 %), 45 (26 %) and 30 (17 %) patients, respectively. Virus-infected patients displayed a high creatine kinase serum level, a low platelet count, and a trend toward more frequent alveolar-interstitial infiltrates. A complicated course was more frequent in the mixed group (31/45, 69 %), as compared to bacterial (18/46, 39 %), viral (15/53, 28 %) and no etiology (12/30, 40 %) groups (p < 0.01). In multivariate analysis, the mixed (viral-bacterial) infection was independently associated with complicated course (reference: bacterial pneumonia; OR, 3.58; CI 95 %, 1.16–11; p = 0.03). The subgroup analysis of bacteria-matched patients confirmed these findings. CONCLUSIONS: Viral-bacterial coinfection during severe CAP in adults is associated with an impaired presentation and a complicated course. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1517-9) contains supplementary material, which is available to authorized users.",2016 Oct 25,"['Voiriot, Guillaume', 'Visseaux, Benoit', 'Cohen, Johana', 'Nguyen, Liem Binh Luong', 'Neuville, Mathilde', 'Morbieu, Caroline', 'Burdet, Charles', 'Radjou, Aguila', 'Lescure, François-Xavier', 'Smonig, Roland', 'Armand-Lefèvre, Laurence', 'Mourvillier, Bruno', 'Yazdanpanah, Yazdan', 'Soubirou, Jean-Francois', 'Ruckly, Stephane', 'Houhou-Fidouh, Nadhira', 'Timsit, Jean-François']",Crit Care,,,True
3024739cfc1f411186c0844a254501c14301c935,PMC,Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study,http://dx.doi.org/10.1371/journal.pmed.1002170,PMC5112802,27846234,CC0,"BACKGROUND: The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. METHODS AND FINDINGS: Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola (“cases”) were asked if they had exposure to other potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO’s response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = −0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). CONCLUSIONS: Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population.",2016 Nov 15,"[None, 'Agua-Agum, Junerlyn', 'Ariyarajah, Archchun', 'Aylward, Bruce', 'Bawo, Luke', 'Bilivogui, Pepe', 'Blake, Isobel M.', 'Brennan, Richard J.', 'Cawthorne, Amy', 'Cleary, Eilish', 'Clement, Peter', 'Conteh, Roland', 'Cori, Anne', 'Dafae, Foday', 'Dahl, Benjamin', 'Dangou, Jean-Marie', 'Diallo, Boubacar', 'Donnelly, Christl A.', 'Dorigatti, Ilaria', 'Dye, Christopher', 'Eckmanns, Tim', 'Fallah, Mosoka', 'Ferguson, Neil M.', 'Fiebig, Lena', 'Fraser, Christophe', 'Garske, Tini', 'Gonzalez, Lice', 'Hamblion, Esther', 'Hamid, Nuha', 'Hersey, Sara', 'Hinsley, Wes', 'Jambei, Amara', 'Jombart, Thibaut', 'Kargbo, David', 'Keita, Sakoba', 'Kinzer, Michael', 'George, Fred Kuti', 'Godefroy, Beatrice', 'Gutierrez, Giovanna', 'Kannangarage, Niluka', 'Mills, Harriet L.', 'Moller, Thomas', 'Meijers, Sascha', 'Mohamed, Yasmine', 'Morgan, Oliver', 'Nedjati-Gilani, Gemma', 'Newton, Emily', 'Nouvellet, Pierre', 'Nyenswah, Tolbert', 'Perea, William', 'Perkins, Devin', 'Riley, Steven', 'Rodier, Guenael', 'Rondy, Marc', 'Sagrado, Maria', 'Savulescu, Camelia', 'Schafer, Ilana J.', 'Schumacher, Dirk', 'Seyler, Thomas', 'Shah, Anita', 'Van Kerkhove, Maria D.', 'Wesseh, C. Samford', 'Yoti, Zabulon']",PLoS Med,,,True
57b5214f988d2e84b41bccd3c704111dc73a8858,PMC,Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study,http://dx.doi.org/10.1371/journal.pmed.1002170,PMC5112802,27846234,CC0,"BACKGROUND: The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. METHODS AND FINDINGS: Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola (“cases”) were asked if they had exposure to other potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO’s response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = −0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). CONCLUSIONS: Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population.",2016 Nov 15,"[None, 'Agua-Agum, Junerlyn', 'Ariyarajah, Archchun', 'Aylward, Bruce', 'Bawo, Luke', 'Bilivogui, Pepe', 'Blake, Isobel M.', 'Brennan, Richard J.', 'Cawthorne, Amy', 'Cleary, Eilish', 'Clement, Peter', 'Conteh, Roland', 'Cori, Anne', 'Dafae, Foday', 'Dahl, Benjamin', 'Dangou, Jean-Marie', 'Diallo, Boubacar', 'Donnelly, Christl A.', 'Dorigatti, Ilaria', 'Dye, Christopher', 'Eckmanns, Tim', 'Fallah, Mosoka', 'Ferguson, Neil M.', 'Fiebig, Lena', 'Fraser, Christophe', 'Garske, Tini', 'Gonzalez, Lice', 'Hamblion, Esther', 'Hamid, Nuha', 'Hersey, Sara', 'Hinsley, Wes', 'Jambei, Amara', 'Jombart, Thibaut', 'Kargbo, David', 'Keita, Sakoba', 'Kinzer, Michael', 'George, Fred Kuti', 'Godefroy, Beatrice', 'Gutierrez, Giovanna', 'Kannangarage, Niluka', 'Mills, Harriet L.', 'Moller, Thomas', 'Meijers, Sascha', 'Mohamed, Yasmine', 'Morgan, Oliver', 'Nedjati-Gilani, Gemma', 'Newton, Emily', 'Nouvellet, Pierre', 'Nyenswah, Tolbert', 'Perea, William', 'Perkins, Devin', 'Riley, Steven', 'Rodier, Guenael', 'Rondy, Marc', 'Sagrado, Maria', 'Savulescu, Camelia', 'Schafer, Ilana J.', 'Schumacher, Dirk', 'Seyler, Thomas', 'Shah, Anita', 'Van Kerkhove, Maria D.', 'Wesseh, C. Samford', 'Yoti, Zabulon']",PLoS Med,,,False
2e45df7e383ca3c79b76fa9f2acc316102386d65,PMC,Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study,http://dx.doi.org/10.1371/journal.pmed.1002170,PMC5112802,27846234,CC0,"BACKGROUND: The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. METHODS AND FINDINGS: Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola (“cases”) were asked if they had exposure to other potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO’s response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = −0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). CONCLUSIONS: Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population.",2016 Nov 15,"[None, 'Agua-Agum, Junerlyn', 'Ariyarajah, Archchun', 'Aylward, Bruce', 'Bawo, Luke', 'Bilivogui, Pepe', 'Blake, Isobel M.', 'Brennan, Richard J.', 'Cawthorne, Amy', 'Cleary, Eilish', 'Clement, Peter', 'Conteh, Roland', 'Cori, Anne', 'Dafae, Foday', 'Dahl, Benjamin', 'Dangou, Jean-Marie', 'Diallo, Boubacar', 'Donnelly, Christl A.', 'Dorigatti, Ilaria', 'Dye, Christopher', 'Eckmanns, Tim', 'Fallah, Mosoka', 'Ferguson, Neil M.', 'Fiebig, Lena', 'Fraser, Christophe', 'Garske, Tini', 'Gonzalez, Lice', 'Hamblion, Esther', 'Hamid, Nuha', 'Hersey, Sara', 'Hinsley, Wes', 'Jambei, Amara', 'Jombart, Thibaut', 'Kargbo, David', 'Keita, Sakoba', 'Kinzer, Michael', 'George, Fred Kuti', 'Godefroy, Beatrice', 'Gutierrez, Giovanna', 'Kannangarage, Niluka', 'Mills, Harriet L.', 'Moller, Thomas', 'Meijers, Sascha', 'Mohamed, Yasmine', 'Morgan, Oliver', 'Nedjati-Gilani, Gemma', 'Newton, Emily', 'Nouvellet, Pierre', 'Nyenswah, Tolbert', 'Perea, William', 'Perkins, Devin', 'Riley, Steven', 'Rodier, Guenael', 'Rondy, Marc', 'Sagrado, Maria', 'Savulescu, Camelia', 'Schafer, Ilana J.', 'Schumacher, Dirk', 'Seyler, Thomas', 'Shah, Anita', 'Van Kerkhove, Maria D.', 'Wesseh, C. Samford', 'Yoti, Zabulon']",PLoS Med,,,False
3fb2c3751fc92b903123c2813868f2b7925c95be,PMC,Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study,http://dx.doi.org/10.1371/journal.pmed.1002170,PMC5112802,27846234,CC0,"BACKGROUND: The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. METHODS AND FINDINGS: Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola (“cases”) were asked if they had exposure to other potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO’s response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = −0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). CONCLUSIONS: Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population.",2016 Nov 15,"[None, 'Agua-Agum, Junerlyn', 'Ariyarajah, Archchun', 'Aylward, Bruce', 'Bawo, Luke', 'Bilivogui, Pepe', 'Blake, Isobel M.', 'Brennan, Richard J.', 'Cawthorne, Amy', 'Cleary, Eilish', 'Clement, Peter', 'Conteh, Roland', 'Cori, Anne', 'Dafae, Foday', 'Dahl, Benjamin', 'Dangou, Jean-Marie', 'Diallo, Boubacar', 'Donnelly, Christl A.', 'Dorigatti, Ilaria', 'Dye, Christopher', 'Eckmanns, Tim', 'Fallah, Mosoka', 'Ferguson, Neil M.', 'Fiebig, Lena', 'Fraser, Christophe', 'Garske, Tini', 'Gonzalez, Lice', 'Hamblion, Esther', 'Hamid, Nuha', 'Hersey, Sara', 'Hinsley, Wes', 'Jambei, Amara', 'Jombart, Thibaut', 'Kargbo, David', 'Keita, Sakoba', 'Kinzer, Michael', 'George, Fred Kuti', 'Godefroy, Beatrice', 'Gutierrez, Giovanna', 'Kannangarage, Niluka', 'Mills, Harriet L.', 'Moller, Thomas', 'Meijers, Sascha', 'Mohamed, Yasmine', 'Morgan, Oliver', 'Nedjati-Gilani, Gemma', 'Newton, Emily', 'Nouvellet, Pierre', 'Nyenswah, Tolbert', 'Perea, William', 'Perkins, Devin', 'Riley, Steven', 'Rodier, Guenael', 'Rondy, Marc', 'Sagrado, Maria', 'Savulescu, Camelia', 'Schafer, Ilana J.', 'Schumacher, Dirk', 'Seyler, Thomas', 'Shah, Anita', 'Van Kerkhove, Maria D.', 'Wesseh, C. Samford', 'Yoti, Zabulon']",PLoS Med,,,False
bae235ec2b6c2fde46fd7c376d5d35933ef4f695,PMC,Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study,http://dx.doi.org/10.1371/journal.pmed.1002170,PMC5112802,27846234,CC0,"BACKGROUND: The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. METHODS AND FINDINGS: Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola (“cases”) were asked if they had exposure to other potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO’s response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = −0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). CONCLUSIONS: Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population.",2016 Nov 15,"[None, 'Agua-Agum, Junerlyn', 'Ariyarajah, Archchun', 'Aylward, Bruce', 'Bawo, Luke', 'Bilivogui, Pepe', 'Blake, Isobel M.', 'Brennan, Richard J.', 'Cawthorne, Amy', 'Cleary, Eilish', 'Clement, Peter', 'Conteh, Roland', 'Cori, Anne', 'Dafae, Foday', 'Dahl, Benjamin', 'Dangou, Jean-Marie', 'Diallo, Boubacar', 'Donnelly, Christl A.', 'Dorigatti, Ilaria', 'Dye, Christopher', 'Eckmanns, Tim', 'Fallah, Mosoka', 'Ferguson, Neil M.', 'Fiebig, Lena', 'Fraser, Christophe', 'Garske, Tini', 'Gonzalez, Lice', 'Hamblion, Esther', 'Hamid, Nuha', 'Hersey, Sara', 'Hinsley, Wes', 'Jambei, Amara', 'Jombart, Thibaut', 'Kargbo, David', 'Keita, Sakoba', 'Kinzer, Michael', 'George, Fred Kuti', 'Godefroy, Beatrice', 'Gutierrez, Giovanna', 'Kannangarage, Niluka', 'Mills, Harriet L.', 'Moller, Thomas', 'Meijers, Sascha', 'Mohamed, Yasmine', 'Morgan, Oliver', 'Nedjati-Gilani, Gemma', 'Newton, Emily', 'Nouvellet, Pierre', 'Nyenswah, Tolbert', 'Perea, William', 'Perkins, Devin', 'Riley, Steven', 'Rodier, Guenael', 'Rondy, Marc', 'Sagrado, Maria', 'Savulescu, Camelia', 'Schafer, Ilana J.', 'Schumacher, Dirk', 'Seyler, Thomas', 'Shah, Anita', 'Van Kerkhove, Maria D.', 'Wesseh, C. Samford', 'Yoti, Zabulon']",PLoS Med,,,False
c59a2273688935323baa77faa5363abd22009134,PMC,Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study,http://dx.doi.org/10.1371/journal.pmed.1002170,PMC5112802,27846234,CC0,"BACKGROUND: The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. METHODS AND FINDINGS: Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola (“cases”) were asked if they had exposure to other potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO’s response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = −0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). CONCLUSIONS: Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population.",2016 Nov 15,"[None, 'Agua-Agum, Junerlyn', 'Ariyarajah, Archchun', 'Aylward, Bruce', 'Bawo, Luke', 'Bilivogui, Pepe', 'Blake, Isobel M.', 'Brennan, Richard J.', 'Cawthorne, Amy', 'Cleary, Eilish', 'Clement, Peter', 'Conteh, Roland', 'Cori, Anne', 'Dafae, Foday', 'Dahl, Benjamin', 'Dangou, Jean-Marie', 'Diallo, Boubacar', 'Donnelly, Christl A.', 'Dorigatti, Ilaria', 'Dye, Christopher', 'Eckmanns, Tim', 'Fallah, Mosoka', 'Ferguson, Neil M.', 'Fiebig, Lena', 'Fraser, Christophe', 'Garske, Tini', 'Gonzalez, Lice', 'Hamblion, Esther', 'Hamid, Nuha', 'Hersey, Sara', 'Hinsley, Wes', 'Jambei, Amara', 'Jombart, Thibaut', 'Kargbo, David', 'Keita, Sakoba', 'Kinzer, Michael', 'George, Fred Kuti', 'Godefroy, Beatrice', 'Gutierrez, Giovanna', 'Kannangarage, Niluka', 'Mills, Harriet L.', 'Moller, Thomas', 'Meijers, Sascha', 'Mohamed, Yasmine', 'Morgan, Oliver', 'Nedjati-Gilani, Gemma', 'Newton, Emily', 'Nouvellet, Pierre', 'Nyenswah, Tolbert', 'Perea, William', 'Perkins, Devin', 'Riley, Steven', 'Rodier, Guenael', 'Rondy, Marc', 'Sagrado, Maria', 'Savulescu, Camelia', 'Schafer, Ilana J.', 'Schumacher, Dirk', 'Seyler, Thomas', 'Shah, Anita', 'Van Kerkhove, Maria D.', 'Wesseh, C. Samford', 'Yoti, Zabulon']",PLoS Med,,,False
15a5a243bb623a17ee4f0c18c4e3bea8c065ed11,PMC,Transmissible Gastroenteritis Virus Infection Enhances SGLT1 and GLUT2 Expression to Increase Glucose Uptake,http://dx.doi.org/10.1371/journal.pone.0165585,PMC5112927,27851758,CC BY,"Transmissible gastroenteritis virus (TGEV) is a coronavirus that causes villus atrophy, followed by crypt hyperplasia, reduces the activities of intestinal digestive enzymes, and disrupts the absorption of intestinal nutrients. In vivo, TGEV primarily targets and infects intestinal epithelial cells, which play an important role in glucose absorption via the apical and basolateral transporters Na(+)-dependent glucose transporter 1 (SGLT1) and facilitative glucose transporter 2 (GLUT2), respectively. In this study, we therefore sought to evaluate the effects of TGEV infection on glucose uptake and SGLT1 and GLUT2 expression. Our data demonstrate that infection with TGEV resulted in increased glucose uptake and augmented expression of EGFR, SGLT1 and GLUT2. Moreover, inhibition studies showed that EGFR modulated glucose uptake in control and TGEV infected cells. Finally, high glucose absorption was subsequently found to promote TGEV replication.",2016 Nov 16,"['Dai, Lei', 'Hu, Wei Wei', 'Xia, Lu', 'Xia, Mi', 'Yang, Qian']",PLoS One,,,True
e55459a4991dbc5ed150ee9174b48401b24517fc,PMC,"Epidemiologic investigation of a family cluster of imported ZIKV cases in Guangdong, China: probable human-to-human transmission",http://dx.doi.org/10.1038/emi.2016.100,PMC5113051,27599469,CC BY,"Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that can potentially threaten South China. A Chinese family of four returning from Venezuela to China was found to be positive for ZIKV when the youngest son's fever was first detected at an airport immigration inspection. They were isolated temporarily in a local hospital in Enping city, Guangdong province, where their clinical data were recorded and urine and saliva were collected to isolate ZIKV and to obtain viral sequences. All of them except the mother presented mild symptoms of rash and fever. Envelope gene sequences from the father, daughter and son were completely identical. Phylogenetic analysis demonstrated that this strain is similar to several imported strains reported in recent months, which are all clustered into a group isolated from 2015 ZIKA outbreaks in Brazil. Together with the climatic features in Venezuela, New York and Guangdong in February, it can be concluded that our subjects are imported cases from Venezuela. With the same viral sequence being shared between family members, neither direct human-to-human nor vector transmission can be ruled out in this study, but the former seems more likely. Although our subjects had mild illness, epidemiologists and public health officials should be aware of the risk of further expansion of ZIKV transmission by local competent vectors.",2016 Sep 7,"['Yin, Yingxian', 'Xu, Yi', 'Su, Ling', 'Zhu, Xun', 'Chen, Minxia', 'Zhu, Weijin', 'Xia, Huimin', 'Huang, Xi', 'Gong, Sitang']",Emerg Microbes Infect,,,True
cc65afbab3c952058f9261b012cdc4407a9d264c,PMC,Evidence that Processing of the Severe Fever with Thrombocytopenia Syndrome Virus Gn/Gc Polyprotein Is Critical for Viral Infectivity and Requires an Internal Gc Signal Peptide,http://dx.doi.org/10.1371/journal.pone.0166013,PMC5113920,27855227,CC BY,"The severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging, highly pathogenic bunyavirus against which neither antivirals nor vaccines are available. The SFTSV glycoproteins, Gn and Gc, facilitate viral entry into host cells. Gn and Gc are generated from a precursor protein, Gn/Gc, but it is currently unknown how the precursor is converted into the single proteins and whether this process is required for viral infectivity. Employing a rhabdoviral pseudotyping system, we demonstrate that a predicted signal sequence at the N-terminus of Gc is required for Gn/Gc processing and viral infectivity while potential proprotein convertase cleavage sites in Gc are dispensable. Moreover, we show that expression of Gn or Gc alone is not sufficient for host cell entry while particles bearing both proteins are infectious, and we provide evidence that Gn facilitates Golgi transport and virion incorporation of Gc. Collectively, these results suggest that signal peptidase liberates mature Gc from the Gn/Gc precursor and that this process is essential for viral infectivity and thus constitutes a potential target for antiviral intervention.",2016 Nov 17,"['Plegge, Teresa', 'Hofmann-Winkler, Heike', 'Spiegel, Martin', 'Pöhlmann, Stefan']",PLoS One,,,True
4d5640c129096fd8a4da9d32030420def86285e5,PMC,Zika (PRVABC59) Infection Is Associated with T cell Infiltration and Neurodegeneration in CNS of Immunocompetent Neonatal C57Bl/6 Mice,http://dx.doi.org/10.1371/journal.ppat.1006004,PMC5113993,27855206,CC0,"The recent spread of Zika virus (ZIKV) and its association with increased rates of Guillain Barre and other neurological disorders as well as congenital defects that include microcephaly has created an urgent need to develop animal models to examine the pathogenesis of the disease and explore the efficacy of potential therapeutics and vaccines. Recently developed infection models for ZIKV utilize mice defective in interferon responses. In this study we establish and characterize a new model of peripheral ZIKV infection using immunocompetent neonatal C57BL/6 mice and compare its clinical progression, virus distribution, immune response, and neuropathology with that of C57BL/6-IFNAR KO mice. We show that while ZIKV infected IFNAR KO mice develop bilateral hind limb paralysis and die 5–6 days post-infection (dpi), immunocompetent B6 WT mice develop signs of neurological disease including unsteady gait, kinetic tremors, severe ataxia and seizures by 13 dpi that subside gradually over 2 weeks. Immunohistochemistry show viral antigen predominantly in cerebellum at the peak of the disease in both models. However, whereas IFNAR KO mice showed infiltration by neutrophils and macrophages and higher expression of IL-1, IL-6 and Cox2, B6 WT mice show a cellular infiltration in the CNS composed predominantly of T cells, particularly CD8+ T cells, and increased mRNA expression levels of IFNg, GzmB and Prf1 at peak of disease. Lastly, the CNS of B6 WT mice shows evidence of neurodegeneration predominantly in the cerebellum that are less prominent in mice lacking the IFN response possibly due to the difference in cellular infiltrates and rapid progression of the disease in that model. The development of the B6 WT model of ZIKV infection will provide insight into the immunopathology of the virus and facilitate assessments of possible therapeutics and vaccines.",2016 Nov 17,"['Manangeeswaran, Mohanraj', 'Ireland, Derek D. C.', 'Verthelyi, Daniela']",PLoS Pathog,,,True
5327ced6851fc0a01061c44f38d7e6c1244dd455,PMC,Zika (PRVABC59) Infection Is Associated with T cell Infiltration and Neurodegeneration in CNS of Immunocompetent Neonatal C57Bl/6 Mice,http://dx.doi.org/10.1371/journal.ppat.1006004,PMC5113993,27855206,CC0,"The recent spread of Zika virus (ZIKV) and its association with increased rates of Guillain Barre and other neurological disorders as well as congenital defects that include microcephaly has created an urgent need to develop animal models to examine the pathogenesis of the disease and explore the efficacy of potential therapeutics and vaccines. Recently developed infection models for ZIKV utilize mice defective in interferon responses. In this study we establish and characterize a new model of peripheral ZIKV infection using immunocompetent neonatal C57BL/6 mice and compare its clinical progression, virus distribution, immune response, and neuropathology with that of C57BL/6-IFNAR KO mice. We show that while ZIKV infected IFNAR KO mice develop bilateral hind limb paralysis and die 5–6 days post-infection (dpi), immunocompetent B6 WT mice develop signs of neurological disease including unsteady gait, kinetic tremors, severe ataxia and seizures by 13 dpi that subside gradually over 2 weeks. Immunohistochemistry show viral antigen predominantly in cerebellum at the peak of the disease in both models. However, whereas IFNAR KO mice showed infiltration by neutrophils and macrophages and higher expression of IL-1, IL-6 and Cox2, B6 WT mice show a cellular infiltration in the CNS composed predominantly of T cells, particularly CD8+ T cells, and increased mRNA expression levels of IFNg, GzmB and Prf1 at peak of disease. Lastly, the CNS of B6 WT mice shows evidence of neurodegeneration predominantly in the cerebellum that are less prominent in mice lacking the IFN response possibly due to the difference in cellular infiltrates and rapid progression of the disease in that model. The development of the B6 WT model of ZIKV infection will provide insight into the immunopathology of the virus and facilitate assessments of possible therapeutics and vaccines.",2016 Nov 17,"['Manangeeswaran, Mohanraj', 'Ireland, Derek D. C.', 'Verthelyi, Daniela']",PLoS Pathog,,,False
e8f7192873a7eab54d8f845f5bf5fc450cbe2e37,PMC,Respiratory viral infections and host responses; insights from genomics,http://dx.doi.org/10.1186/s12931-016-0474-9,PMC5117516,27871304,CC BY,"Respiratory viral infections are a leading cause of disease and mortality. The severity of these illnesses can vary markedly from mild or asymptomatic upper airway infections to severe wheezing, bronchiolitis or pneumonia. In this article, we review the viral sensing pathways and organizing principles that govern the innate immune response to infection. Then, we reconstruct the molecular networks that differentiate symptomatic from asymptomatic respiratory viral infections, and identify the underlying molecular drivers of these networks. Finally, we discuss unique aspects of the biology and pathogenesis of infections with respiratory syncytial virus, rhinovirus and influenza, drawing on insights from genomics.",2016 Nov 21,"['Troy, Niamh M.', 'Bosco, Anthony']",Respir Res,,,True
8be925093133c499cb2c93e36d9bf0fdb24c2eda,PMC,"Ebola, Zika and the International Health Regulations – implications for Port Health Preparedness",http://dx.doi.org/10.1186/s12992-016-0173-9,PMC5117607,27871327,CC BY,"BACKGROUND: The outbreak of Ebola Virus Disease in West Africa in 2014-2015 was unprecedented in terms of its scale and consequence.  This, together with the emergence of Zika virus as a Public Health Emergency of International Concern in 2016, has again highlighted the potential for disease to spread across international borders and provided an impetus for countries to review their Port Health preparedness. This report reviews the legislative framework and actions taken under this framework in advancing and improving Port Health preparedness in Ireland, in response to the declaration of the Public Health Emergency of International Concern for Ebola Virus Disease in August 2014. FINDINGS: Infectious disease Shipping and Aircraft Regulations were brought into force in Ireland in 2008 and 2009, respectively. Preparatory actions taken under these and the International Health Regulations necessitated significant levels of cross disciplinary working with other organisations, both within and beyond traditional healthcare settings. Information packs on Ebola Virus Disease were prepared and distributed to airports, airlines, port authorities and shipping agents, and practical exercises were held at relevant sites. Agreements were put in place for contact tracing of passenger and crew on affected conveyances and protocols were established for the management of Medical Declarations of Health from ships coming from West Africa. CONCLUSIONS: The outbreak of Ebola Virus Disease in West Africa resulted in significant strengthening of Ireland’s Port Health preparedness, while also highlighting the extent to which preparedness requires ongoing and sustained commitment from all stakeholders, both nationally and internationally, in ensuring that countries are ready when the next threat presents at their borders.",2016 Nov 21,"['Glynn, R. W.', 'Boland, M.', None]",Global Health,,,True
c6e2851ef1f6e35c2954eeaa913f2da2502842d9,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,True
e8fee5ad6649972750c54158e4fff759beb12d3b,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,False
46bbc1a9a5cb04f9e2156e26842f1aa6d1ead14a,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,False
9871ce7a904960426816c71415696441aff8bcc3,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,False
0d40a575b734448ffdb8b7e20db9075295c4dbf2,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,False
4be99efe3b1b8c8a1ea1fad11a541ad437798ee7,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,False
a98cc3c7c41072d33b8382a8b6fb2cac6243e598,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,False
0d1b4776233a32404ee6fcba5cac809e15e3732f,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,False
ea6b9bf12c54a99f7304353af992637e589a0eef,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,False
b7de4f4a99e8da86891ed28bca52afcbcbdabfa1,PMC,Increased frequency of porcine epidemic diarrhea virus shedding and lesions in suckling pigs compared to nursery pigs and protective immunity in nursery pigs after homologous re-challenge,http://dx.doi.org/10.1186/s13567-016-0402-5,PMC5118895,27871312,CC BY,"Porcine epidemic diarrhea virus (PEDV) causes enteric disease in pigs and spreads rapidly after entering naïve pig populations. The objectives were to (1) compare the disease course following inoculation with PEDV isolate US/Colorado/2013 in naïve 10 day and 8 week-old pigs, and (2) contrast the naïve response to homologous challenge in 8 week-old pigs. Pigs were randomly assigned into group 1 (n = 40, no PEDV exposure), group 2 (n = 43, PEDV inoculation at 10 days of age) and group 3 (n = 48, PEDV inoculation at 8 weeks of age). Thirty-three group 2 pigs received a homologous challenge at 8 weeks of age. Following primary or secondary inoculation, 3–10 pigs were euthanized at days post-inoculation (dpi) 1, 2, 3, 7 or 14. Clinical signs were more pronounced in 10 day-old pigs compared to 8 week-old pigs at dpi 2 and 3, a higher number of 10 day-old pigs shed PEDV RNA in feces compared to 8 week-old pigs. Typical severe atrophic enteritis of PEDV infection was observed at dpi 3 in both age groups, and at dpi 4 and 14 fecal shedding patterns were also similar. While both age groups had seroconverted to PEDV by dpi 14, IgG levels were higher in 8 week-old pigs. PEDV IgA antibodies were detected in feces of approximately 50% of the pigs at dpi 44. In homologous challenged pigs, no clinical signs or lesions were found, and PEDV fecal shedding was restricted to less than 10% of the pigs indicating the existence of homologous protection 44 days after initial PEDV exposure.",2016 Nov 21,"['Gerber, Priscilla F.', 'Xiao, Chao-Ting', 'Lager, Kelly', 'Crawford, Kimberly', 'Kulshreshtha, Vikas', 'Cao, Dianjun', 'Meng, Xiang-Jin', 'Opriessnig, Tanja']",Vet Res,,,True
f421ab87adfb959664409ada2f3849ec1a977320,PMC,"Enterovirus D68 in Hospitalized Children: Sequence Variation, Viral Loads and Clinical Outcomes",http://dx.doi.org/10.1371/journal.pone.0167111,PMC5119825,27875593,CC BY,"BACKGROUND: An outbreak of enterovirus D68 (EV-D68) caused severe respiratory illness in 2014. The disease spectrum of EV-D68 infections in children with underlying medical conditions other than asthma, the role of EV-D68 loads on clinical illness, and the variation of EV-D68 strains within the same institution over time have not been described. We sought to define the association between EV-D68 loads and sequence variation, and the clinical characteristic in hospitalized children at our institution from 2011 to 2014. METHODS: May through November 2014, and August to September 2011 to 2013, a convenience sample of nasopharyngeal specimens from children with rhinovirus (RV)/EV respiratory infections were tested for EV-D68 by RT-PCR. Clinical data were compared between children with RV/EV-non-EV-D68 and EV-D68 infections, and among children with EV-D68 infections categorized as healthy, asthmatics, and chronic medical conditions. EV-D68 loads were analyzed in relation to disease severity parameters and sequence variability characterized over time. RESULTS: In 2014, 44% (192/438) of samples tested positive for EV-D68 vs. 10% (13/130) in 2011–13 (p<0.0001). PICU admissions (p<0.0001) and non-invasive ventilation (p<0.0001) were more common in children with EV-D68 vs. RV/EV-non-EV-D68 infections. Asthmatic EV-D68+ children, required supplemental oxygen administration (p = 0.03) and PICU admissions (p <0.001) more frequently than healthy children or those with chronic medical conditions; however oxygen duration (p<0.0001), and both PICU and total hospital stay (p<0.01) were greater in children with underlying medical conditions, irrespective of viral burden. By phylogenetic analysis, the 2014 EV-D68 strains clustered into a new sublineage within clade B. CONCLUSIONS: This is one of the largest pediatric cohorts described from the EV-D68 outbreak. Irrespective of viral loads, EV-D68 was associated with high morbidity in children with asthma and co-morbidities. While EV-D68 circulated before 2014, the outbreak isolates clustered differently than those from prior years.",2016 Nov 22,"['Moyer, Katherine', 'Wang, Huanyu', 'Salamon, Douglas', 'Leber, Amy', 'Mejias, Asuncion']",PLoS One,,,True
c933e09cb9262b2edc2394b1a7d86357da840493,PMC,High Diversity of Genogroup I Picobirnaviruses in Mammals,http://dx.doi.org/10.3389/fmicb.2016.01886,PMC5120130,27933049,CC BY,"In a molecular epidemiology study using 791 fecal samples collected from different terrestrial and marine mammals in Hong Kong, genogroup I picobirnaviruses (PBVs) were positive by RT-PCR targeting the partial RdRp gene in specimens from five cattle, six monkeys, 17 horses, nine pigs, one rabbit, one dog, and 12 California sea lions, with 11, 9, 23, 17, 1, 1, and 15 sequence types in the positive specimens from the corresponding animals, respectively. Phylogenetic analysis showed that the PBV sequences from each kind of animal were widely distributed in the whole tree with high diversity, sharing 47.4–89.0% nucleotide identities with other genogroup I PBV strains based on the partial RdRp gene. Nine complete segment 1 (viral loads 1.7 × 10(4) to 5.9 × 10(6)/ml) and 15 segment 2 (viral loads 4.1 × 10(3) to 1.3 × 10(6)/ml) of otarine PBVs from fecal samples serially collected from California sea lions were sequenced. In the two phylogenetic trees constructed using ORF2 and ORF3 of segment 1, the nine segment 1 sequences were clustered into four distinct clades (C1–C4). In the tree constructed using RdRp gene of segment 2, the 15 segment 2 sequences were clustered into nine distinct clades (R1–R9). In four sea lions, PBVs were detected in two different years, with the same segment 1 clade (C3) present in two consecutive years from one sea lion and different clades present in different years from three sea lions. A high diversity of PBVs was observed in a variety of terrestrial and marine mammals. Multiple sequence types with significant differences, representing multiple strains of PBV, were present in the majority of PBV-positive samples from different kinds of animals.",2016 Nov 23,"['Woo, Patrick C. Y.', 'Teng, Jade L. L.', 'Bai, Ru', 'Wong, Annette Y. P.', 'Martelli, Paolo', 'Hui, Suk-Wai', 'Tsang, Alan K. L.', 'Lau, Candy C. Y.', 'Ahmed, Syed S.', 'Yip, Cyril C. Y.', 'Choi, Garnet K. Y.', 'Li, Kenneth S. M.', 'Lam, Carol S. F.', 'Lau, Susanna K. P.', 'Yuen, Kwok-Yung']",Front Microbiol,,,True
94ccf97f5df377bf432fa3a831e38f11985965bd,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,True
e435b69dbcf8f58770a536cd0f429238fa3368f6,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
3b831e1792c447aed55f2eee0c1d0c75b2372dbb,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
2fa60d44d0d8c4737fd1e18d9b046f584bea2549,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
4c8110bfcde6d110c4a455f7bb8ea1a7801e8434,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
db36b989b9a9b5e309143650fca156e2613c034d,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
b9e757940f9d429f2684ee74b0e965f888ed973e,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
0f3ed61e7fb715fd7fdbc2e3a302b6b879e9b2af,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
b0089c74fa2043dfa4ffe2823b080792ca14ad76,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
ba70c25d879ca4243b2e05433c4e77efe3e4e263,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
8f0f34b6fdee81589f6e57a784dc4bafb0a9a6a1,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
d7803599fa57f39b06d7fd5bc8986420ae13fc2c,PMC,"Identification of an infectious bronchitis coronavirus strain exhibiting a classical genotype but altered antigenicity, pathogenicity, and innate immunity profile",http://dx.doi.org/10.1038/srep37725,PMC5120290,27876864,CC BY,"Avian coronavirus infectious bronchitis virus (IBV) poses economic threat to the poultry industry worldwide. Pathogenic IBV 3575/08 was isolated from broilers vaccinated with the attenuated viral vaccine derived from a Taiwan strain 2575/98. In this study, extensive investigations were conducted on the genome sequences, antigenicity, pathogenicity, and host immune responses of several IBV strains in specific-pathogen-free chickens. Sequence analyses revealed that 3575/08 and 2575/98 shared high homology in their structural genes, but not in non-structural accessory proteins such as 3a, 3b and 5b. Despite a high degree of homology in their spike protein genes, cross neutralization test showed low cross protection between 3575/08 and 2575/98, suggesting distinct antigenicity for the two strains. Animal challenge experiments exhibited strong respiratory and renal pathogenicity for 3575/08. In addition, early and prolonged viral shedding and rapid viral dissemination were observed. Immune gene expression profiling by PCR array showed chickens infected with 3575/08 had delayed expression of a subset of early innate immune genes, whereas chickens infected with the wild-type or attenuated-type 2575/08 revealed quick gene induction and efficient virus control. In summary, this study reveals a new IBV strain, which harbors a known local genotype but displays remarkably altered antigenicity, pathogenicity and host defenses.",2016 Nov 23,"['Lin, Shu-Yi', 'Li, Yao-Tsun', 'Chen, You-Ting', 'Chen, Ting-Chih', 'Hu, Che-Ming J.', 'Chen, Hui-Wen']",Sci Rep,,,True
8aa377ebe7d8486e4d0e38f6542eb40c0ab31847,PMC,"Identification of an infectious bronchitis coronavirus strain exhibiting a classical genotype but altered antigenicity, pathogenicity, and innate immunity profile",http://dx.doi.org/10.1038/srep37725,PMC5120290,27876864,CC BY,"Avian coronavirus infectious bronchitis virus (IBV) poses economic threat to the poultry industry worldwide. Pathogenic IBV 3575/08 was isolated from broilers vaccinated with the attenuated viral vaccine derived from a Taiwan strain 2575/98. In this study, extensive investigations were conducted on the genome sequences, antigenicity, pathogenicity, and host immune responses of several IBV strains in specific-pathogen-free chickens. Sequence analyses revealed that 3575/08 and 2575/98 shared high homology in their structural genes, but not in non-structural accessory proteins such as 3a, 3b and 5b. Despite a high degree of homology in their spike protein genes, cross neutralization test showed low cross protection between 3575/08 and 2575/98, suggesting distinct antigenicity for the two strains. Animal challenge experiments exhibited strong respiratory and renal pathogenicity for 3575/08. In addition, early and prolonged viral shedding and rapid viral dissemination were observed. Immune gene expression profiling by PCR array showed chickens infected with 3575/08 had delayed expression of a subset of early innate immune genes, whereas chickens infected with the wild-type or attenuated-type 2575/08 revealed quick gene induction and efficient virus control. In summary, this study reveals a new IBV strain, which harbors a known local genotype but displays remarkably altered antigenicity, pathogenicity and host defenses.",2016 Nov 23,"['Lin, Shu-Yi', 'Li, Yao-Tsun', 'Chen, You-Ting', 'Chen, Ting-Chih', 'Hu, Che-Ming J.', 'Chen, Hui-Wen']",Sci Rep,,,False
f4a82ad66962355ffb09e4d1b57fde3e94f0ec53,PMC,Regulation and Maintenance of an Adoptive T-Cell Dependent Memory B Cell Pool,http://dx.doi.org/10.1371/journal.pone.0167003,PMC5120830,27880797,CC BY,"We investigated the ability of monoclonal B cells to restore primary and secondary T-cell dependent antibody responses in adoptive immune-deficient hosts. Priming induced B cell activation and expansion, AID expression, antibody production and the generation of IgM(+)IgG(-) and IgM(-)IgG(+) antigen-experienced B-cell subsets that persisted in the lymphopenic environment by cell division. Upon secondary transfer and recall the IgM(-)IgG(+) cells responded by the production of antigen-specific IgG while the IgM(+) memory cells secreted mainly IgM and little IgG, but generated new B cells expressing germinal center markers. The recall responses were more efficient if the antigenic boost was delayed suggesting that a period of adaptation is necessary before the transferred cells are able to respond. Overall these findings indicate that reconstitution of a functional and complete memory pool requires transfer of all different antigen-experienced B cell subsets. We also found that the size of the memory B cell pool did not rely on the number of the responding naïve B cells, suggesting autonomous homeostatic controls for naïve and memory B cells. By reconstituting a stable memory B cell pool in immune-deficient hosts using a monoclonal high-affinity B cell population we demonstrate the potential value of B cell adoptive immunotherapy.",2016 Nov 23,"['Anson, Marie', 'Amado, Inês', 'Mailhé, Marie-Pierre', 'Donnadieu, Emmanuel', 'Garcia, Sylvie', 'Huetz, François', 'Freitas, Antonio A.']",PLoS One,,,True
0792384d074cef963c808eacf3c63e3654776a2a,PMC,Viral Infection in the Development and Progression of Pediatric Acute Respiratory Distress Syndrome,http://dx.doi.org/10.3389/fped.2016.00128,PMC5121220,27933286,CC BY,"Viral infections are an important cause of pediatric acute respiratory distress syndrome (ARDS). Numerous viruses, including respiratory syncytial virus (RSV) and influenza A (H1N1) virus, have been implicated in the progression of pneumonia to ARDS; yet the incidence of progression is unknown. Despite acute and chronic morbidity associated with respiratory viral infections, particularly in “at risk” populations, treatment options are limited. Thus, with few exceptions, care is symptomatic. In addition, mortality rates for viral-related ARDS have yet to be determined. This review outlines what is known about ARDS secondary to viral infections including the epidemiology, the pathophysiology, and diagnosis. In addition, emerging treatment options to prevent infection, and to decrease disease burden will be outlined. We focused on RSV and influenza A (H1N1) viral-induced ARDS, as these are the most common viruses leading to pediatric ARDS, and have specific prophylactic and definitive treatment options.",2016 Nov 24,"['Nye, Steven', 'Whitley, Richard J.', 'Kong, Michele']",Front Pediatr,,,True
985f2253ef842c0bd15013ac3314061d880d12a4,PMC,Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines,http://dx.doi.org/10.1038/ncomms13473,PMC5121417,27874853,CC BY,"Viral subunit vaccines often contain immunodominant non-neutralizing epitopes that divert host immune responses. These epitopes should be eliminated in vaccine design, but there is no reliable method for evaluating an epitope's capacity to elicit neutralizing immune responses. Here we introduce a new concept ‘neutralizing immunogenicity index' (NII) to evaluate an epitope's neutralizing immunogenicity. To determine the NII, we mask the epitope with a glycan probe and then assess the epitope's contribution to the vaccine's overall neutralizing immunogenicity. As proof-of-concept, we measure the NII for different epitopes on an immunogen comprised of the receptor-binding domain from MERS coronavirus (MERS-CoV). Further, we design a variant form of this vaccine by masking an epitope that has a negative NII score. This engineered vaccine demonstrates significantly enhanced efficacy in protecting transgenic mice from lethal MERS-CoV challenge. Our study may guide the rational design of highly effective subunit vaccines to combat MERS-CoV and other life-threatening viruses.",2016 Nov 22,"['Du, Lanying', 'Tai, Wanbo', 'Yang, Yang', 'Zhao, Guangyu', 'Zhu, Qing', 'Sun, Shihui', 'Liu, Chang', 'Tao, Xinrong', 'Tseng, Chien-Te K.', 'Perlman, Stanley', 'Jiang, Shibo', 'Zhou, Yusen', 'Li, Fang']",Nat Commun,,,True
d98fdaef5cdea0bb192c21a1a234df3d506290d6,PMC,Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines,http://dx.doi.org/10.1038/ncomms13473,PMC5121417,27874853,CC BY,"Viral subunit vaccines often contain immunodominant non-neutralizing epitopes that divert host immune responses. These epitopes should be eliminated in vaccine design, but there is no reliable method for evaluating an epitope's capacity to elicit neutralizing immune responses. Here we introduce a new concept ‘neutralizing immunogenicity index' (NII) to evaluate an epitope's neutralizing immunogenicity. To determine the NII, we mask the epitope with a glycan probe and then assess the epitope's contribution to the vaccine's overall neutralizing immunogenicity. As proof-of-concept, we measure the NII for different epitopes on an immunogen comprised of the receptor-binding domain from MERS coronavirus (MERS-CoV). Further, we design a variant form of this vaccine by masking an epitope that has a negative NII score. This engineered vaccine demonstrates significantly enhanced efficacy in protecting transgenic mice from lethal MERS-CoV challenge. Our study may guide the rational design of highly effective subunit vaccines to combat MERS-CoV and other life-threatening viruses.",2016 Nov 22,"['Du, Lanying', 'Tai, Wanbo', 'Yang, Yang', 'Zhao, Guangyu', 'Zhu, Qing', 'Sun, Shihui', 'Liu, Chang', 'Tao, Xinrong', 'Tseng, Chien-Te K.', 'Perlman, Stanley', 'Jiang, Shibo', 'Zhou, Yusen', 'Li, Fang']",Nat Commun,,,False
bca82a8723c167333ef1d73d5bf0fd900f30b695,PMC,Phenotypic and functional characterization of the major lymphocyte populations in the fruit-eating bat Pteropus alecto,http://dx.doi.org/10.1038/srep37796,PMC5121612,27883085,CC BY,"The unique ability of bats to act as reservoir for viruses that are highly pathogenic to humans suggests unique properties and functional characteristics of their immune system. However, the lack of bat specific reagents, in particular antibodies, has limited our knowledge of bat’s immunity. Using cross-reactive antibodies, we report the phenotypic and functional characterization of T cell subsets, B and NK cells in the fruit-eating bat Pteropus alecto. Our findings indicate the predominance of CD8(+) T cells in the spleen from wild-caught bats that may reflect either the presence of viruses in this organ or predominance of this cell subset at steady state. Instead majority of T cells in circulation, lymph nodes and bone marrow (BM) were CD4(+) subsets. Interestingly, 40% of spleen T cells expressed constitutively IL-17, IL-22 and TGF-β mRNA, which may indicate a strong bias towards the Th17 and regulatory T cell subsets. Furthermore, the unexpected high number of T cells in bats BM could suggest an important role in T cell development. Finally, mitogenic stimulation induced proliferation and production of effector molecules by bats immune cells. This work contributes to a better understanding of bat’s immunity, opening up new perspectives of therapeutic interventions for humans.",2016 Nov 24,"['Martínez Gómez, Julia María', 'Periasamy, Pravin', 'Dutertre, Charles-Antoine', 'Irving, Aaron Trent', 'Ng, Justin Han Jia', 'Crameri, Gary', 'Baker, Michelle L.', 'Ginhoux, Florent', 'Wang, Lin-Fa', 'Alonso, Sylvie']",Sci Rep,,,True
65aad42469b115f496dac7fe5b1a74ee5bbbf93e,PMC,Mint3/Apba3 depletion ameliorates severe murine influenza pneumonia and macrophage cytokine production in response to the influenza virus,http://dx.doi.org/10.1038/srep37815,PMC5121658,27883071,CC BY,"Influenza virus (IFV) infection is a common cause of severe pneumonia. Studies have suggested that excessive activation of the host immune system including macrophages is responsible for the severe pathologies mediated by IFV infection. Here, we focused on the X11 protein family member Mint3/Apba3, known to promote ATP production via glycolysis by activating hypoxia inducible factor-1 (HIF-1) in macrophages, and examined its roles in lung pathogenesis and anti-viral defence upon IFV infection. Mint3-deficient mice exhibited improved influenza pneumonia with reduced inflammatory cytokines/chemokine levels and neutrophil infiltration in the IFV-infected lungs without alteration in viral burden, type-I interferon production, or acquired immunity. In macrophages, Mint3 depletion attenuated NF-κB signalling and the resultant cytokine/chemokine production in response to IFV infection by increasing IκBα and activating the cellular energy sensor AMPK, respectively. Thus, Mint3 might represent one of the likely therapeutic targets for the treatment of severe influenza pneumonia without affecting host anti-viral defence through suppressing macrophage cytokine/chemokine production.",2016 Nov 24,"['Uematsu, Takayuki', 'Fujita, Tomoko', 'Nakaoka, Hiroki J.', 'Hara, Toshiro', 'Kobayashi, Noritada', 'Murakami, Yoshinori', 'Seiki, Motoharu', 'Sakamoto, Takeharu']",Sci Rep,,,True
1c55462ba94ea026e0aef29ad6dbed4520990158,PMC,Mint3/Apba3 depletion ameliorates severe murine influenza pneumonia and macrophage cytokine production in response to the influenza virus,http://dx.doi.org/10.1038/srep37815,PMC5121658,27883071,CC BY,"Influenza virus (IFV) infection is a common cause of severe pneumonia. Studies have suggested that excessive activation of the host immune system including macrophages is responsible for the severe pathologies mediated by IFV infection. Here, we focused on the X11 protein family member Mint3/Apba3, known to promote ATP production via glycolysis by activating hypoxia inducible factor-1 (HIF-1) in macrophages, and examined its roles in lung pathogenesis and anti-viral defence upon IFV infection. Mint3-deficient mice exhibited improved influenza pneumonia with reduced inflammatory cytokines/chemokine levels and neutrophil infiltration in the IFV-infected lungs without alteration in viral burden, type-I interferon production, or acquired immunity. In macrophages, Mint3 depletion attenuated NF-κB signalling and the resultant cytokine/chemokine production in response to IFV infection by increasing IκBα and activating the cellular energy sensor AMPK, respectively. Thus, Mint3 might represent one of the likely therapeutic targets for the treatment of severe influenza pneumonia without affecting host anti-viral defence through suppressing macrophage cytokine/chemokine production.",2016 Nov 24,"['Uematsu, Takayuki', 'Fujita, Tomoko', 'Nakaoka, Hiroki J.', 'Hara, Toshiro', 'Kobayashi, Noritada', 'Murakami, Yoshinori', 'Seiki, Motoharu', 'Sakamoto, Takeharu']",Sci Rep,,,False
784b8019936ae21771682f1184ff3fe10cc40b6f,PMC,The Ebola Outbreak: Catalyzing a “Shift” in Global Health Governance?,http://dx.doi.org/10.1186/s12879-016-2016-y,PMC5121963,27881085,CC BY,"BACKGROUND: As the 2014 Ebola virus disease outbreak (EVD) transitions to its post-endemic phase, its impact on the future of global public health, particularly the World Health Organization (WHO), is the subject of continued debate. Criticism of WHO’s performance grew louder in the outbreak’s wake, placing this international health UN-specialized agency in the difficult position of navigating a complex series of reform recommendations put forth by different stakeholders. Decisions on WHO governance reform and the broader role of the United Nations could very well shape the future landscape of 21st century global health and how the international community responds to health emergencies. DISCUSSION: In order to better understand the implications of the EVD outbreak on global health and infectious disease governance, this debate article critically examines a series of reports issued by four high-level commissions/panels convened to specifically assess WHO’s performance post-Ebola. Collectively, these recommendations add increasing complexity to the urgent need for WHO reform, a process that the agency must carry out in order to maintain its legitimacy. Proposals that garnered strong support included the formation of an independent WHO Centre for Emergency Preparedness and Response, the urgent need to increase WHO infectious disease funding and capacity, and establishing better operational and policy coordination between WHO, UN agencies, and other global health partners. The recommendations also raise more fundamental questions about restructuring the global health architecture, and whether the UN should play a more active role in global health governance. SUMMARY: Despite the need for a fully modernized WHO, reform proposals recently announced by WHO fail to achieve the “evolution” in global health governance needed in order to ensure that global society is adequately protected against the multifaceted and increasingly complex nature of modern public health emergencies. Instead, the lasting legacy of the EVD outbreak may be its foreshadowing of a governance “shift” in formal sharing of the complex responsibilities of global health, health security, outbreak response, and managing health emergencies to other international structures, most notably the United Nations. Only time will tell if the legacy of EVD will include a WHO that has the full support of the international community and is capable of leading human society in this brave new era of the globalization of infectious diseases.",2016 Nov 24,"Mackey, Tim K.",BMC Infect Dis,,,True
b6d7e94615aea8a7a591d68cea8c6710ce86df13,PMC,Anti-tumor effects of Abnormal Savda Munziq on the transplanted cervical cancer (U27) mouse model,http://dx.doi.org/10.1186/s12906-016-1458-5,PMC5122163,27881109,CC BY,"BACKGROUND: Abnormal Savda Munziq (ASMq), a traditional uyghur medicine, has shown anti-tumour properties in vitro. it was showed that total flavonoids of ASMq could inhibit the proliferation and enhance the antioxidant ability of human cervix cancer HeLa cell. This study attempts to confirm these effects on the transplanted cervical cancer (U27) mouse model in vivo. METHODS: Forty eight Kunming mice were randomly divided in to six groups: normal control group (Control group), U27 tumor model group (Model group), cyclophosphamide administration group (CTX group),low-dose ASMq group (ASMq.L group), medium-dose ASMq group (ASMq.M group), and high-dose ASMq group (ASMq.H group). The five groups except normal control group transplanted with cervical cancer (U27) cells. We observed mice tumor inhibition rate and conducted the histopathological analysisUsing the western blot assay, the expression of TGF-β1 and TNF-α protein in transplanted cervical cancer U27 tumor tissue were detected. RESULTS: The tumor inhibition rates of CTX group, ASMq.L group, ASMq.M group, and ASMq.H group were 72.21, 31.27, 60.53 and 51.94% respectively, has obvious antitumor effect. ASMq significantly promote the spleen tlymphocyte proliferation of transplanted cervical cancer U27 mice. Invasive growth and diffusion rate in tumor tissue were accelerate in the transplanted cervical cancer U27 model group. Tumor tissue necrosis of tumor cells are smaller in the medium, high dosage group. Compared with the U27 model group, the expression levels of TGF-β1 protein and TNF-α protein expression exhibited statistically significant decreased in the mice tumor tissues in the CTX administration group and the ASMq administration group. CONCLUSIONS: ASMq has some antitumor effects on U27 model mice in vivo, The effects are achieved not only by improving the immune function of U27 model mice, but also by inhibiting the expression levels of TGF-β1 protein while promoting the expression levels of TNF-α protein.",2016 Nov 24,"['Omarniyaz, Zuhragul', 'Yu, Yang', 'Yang, Tao', 'Shan, Lianlian', 'Miao, Weiwei', 'Reyimu, Renaguli', 'Upur, Halmurat', 'Aikemu, Ainiwaer']",BMC Complement Altern Med,,,True
7d00b513342aa0cdedd01900540fabffe9f54207,PMC,Disinfection of aircraft: Appropriate disinfectants and standard operating procedures for highly infectious diseases,http://dx.doi.org/10.1007/s00103-016-2460-2,PMC5122611,27785522,CC BY,"For infectious diseases caused by highly pathogenic agents (e. g., Ebola/Lassa fever virus, SARS-/MERS-CoV, pandemic influenza virus) which have the potential to spread over several continents within only a few days, international Health Protection Authorities have taken appropriate measures to limit the consequences of a possible spread. A crucial point in this context is the disinfection of an aircraft that had a passenger on board who is suspected of being infected with one of the mentioned diseases. Although, basic advice on hygiene and sanitation on board an aircraft is given by the World Health Organization, these guidelines lack details on available and effective substances as well as standardized operating procedures (SOP). The purpose of this paper is to give guidance on the choice of substances that were tested by a laboratory of Lufthansa Technik and found compatible with aircraft components, as well as to describe procedures which ensure a safe and efficient disinfection of civil aircrafts. This guidance and the additional SOPs are made public and are available as mentioned in this paper.",2016 Oct 26,"['Klaus, Joachim', 'Gnirs, Peter', 'Hölterhoff, Sabine', 'Wirtz, Angela', 'Jeglitza, Matthias', 'Gaber, Walter', 'Gottschalk, Rene']",Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz,,,True
1a485210a47a7eb2d39964a350d68ae52368c1df,PMC,Isolation and characterization of adenoviruses infecting endangered golden snub-nosed monkeys (Rhinopithecus roxellana),http://dx.doi.org/10.1186/s12985-016-0648-6,PMC5123214,27884154,CC BY,"BACKGROUND: Adenoviruses are important pathogens with the potential for interspecies transmission between humans and non-human primates. Although many adenoviruses have been identified in monkeys, the knowledge of these viruses from the Colobinae members is quite limited. FINDINGS: We conducted a surveillance of viral infection in endangered golden snub-nosed monkeys (Rhinopithecus roxellana) in the subfamily Colobinae in China, and found that 5.1% of sampled individuals were positive for adenovirus. One of the adenoviruses (SAdV-WIV19) was successfully isolated and its full-length genome was sequenced. The full-length genome of WIV19 is 33,562 bp in size, has a G + C content of 56.2%, and encodes 35 putative genes. Sequence analysis revealed that this virus represents a novel species in the genus Mastadenovirus. Diverse cell lines, including those of human origin, were susceptible to WIV19. CONCLUSION: We report the first time the isolation and full-length genomic characterization of an adenovirus from the subfamily Colobinae. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0648-6) contains supplementary material, which is available to authorized users.",2016 Nov 25,"['Tan, Bing', 'Wu, Li-Jun', 'Yang, Xing-Lou', 'Li, Bei', 'Zhang, Wei', 'Lei, Yong-Song', 'Li, Yong', 'Yang, Guo-Xiang', 'Chen, Jing', 'Chen, Guang', 'Wang, Han-Zhong', 'Shi, Zheng-Li']",Virol J,,,True
f81a5f06d5cbc6998bddce29a3eb508d8ceb83f7,PMC,Angiotensin-converting enzyme 2 is reduced in Alzheimer’s disease in association with increasing amyloid-β and tau pathology,http://dx.doi.org/10.1186/s13195-016-0217-7,PMC5123239,27884212,CC BY,"BACKGROUND: Hyperactivity of the classical axis of the renin-angiotensin system (RAS), mediated by angiotensin II (Ang II) activation of the angiotensin II type 1 receptor (AT1R), is implicated in the pathogenesis of Alzheimer’s disease (AD). Angiotensin-converting enzyme-2 (ACE-2) degrades Ang II to angiotensin 1–7 (Ang (1-7)) and counter-regulates the classical axis of RAS. We have investigated the expression and distribution of ACE-2 in post-mortem human brain tissue in relation to AD pathology and classical RAS axis activity. METHODS: We measured ACE-2 activity by fluorogenic peptide substrate assay in mid-frontal cortex (Brodmann area 9) in a cohort of AD (n = 90) and age-matched non-demented controls (n = 59) for which we have previous data on ACE-1 activity, amyloid β (Aβ) level and tau pathology, as well as known ACE1 (rs1799752) indel polymorphism, apolipoprotein E (APOE) genotype, and cerebral amyloid angiopathy severity scores. RESULTS: ACE-2 activity was significantly reduced in AD compared with age-matched controls (P < 0.0001) and correlated inversely with levels of Aβ (r = −0.267, P < 0.001) and phosphorylated tau (p-tau) pathology (r = −0.327, P < 0.01). ACE-2 was reduced in individuals possessing an APOE ε4 allele (P < 0.05) and was associated with ACE1 indel polymorphism (P < 0.05), with lower ACE-2 activity in individuals homozygous for the ACE1 insertion AD risk allele. ACE-2 activity correlated inversely with ACE-1 activity (r = −0.453, P < 0.0001), and the ratio of ACE-1 to ACE-2 was significantly elevated in AD (P < 0.0001). Finally, we show that the ratio of Ang II to Ang (1–7) (a proxy measure of ACE-2 activity indicating  conversion of Ang II to Ang (1–7)) is reduced in AD. CONCLUSIONS: Together, our findings indicate that ACE-2 activity is reduced in AD and is an important regulator of the central classical ACE-1/Ang II/AT1R axis of RAS, and also that dysregulation of this pathway likely plays a significant role in the pathogenesis of AD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13195-016-0217-7) contains supplementary material, which is available to authorized users.",2016 Nov 25,"['Kehoe, Patrick Gavin', 'Wong, Steffenny', 'AL Mulhim, Noura', 'Palmer, Laura Elyse', 'Miners, J. Scott']",Alzheimers Res Ther,,,True
3c082fd7a87e4e55f001e749fa9ce2a3481b0f5f,PMC,A bibliometric analysis of literature on malaria vector resistance: (1996 – 2015),http://dx.doi.org/10.1186/s12992-016-0214-4,PMC5123357,27884199,CC BY,"BACKGROUND: Emergence of insecticide resistance in malaria vectors is a real threat to future goals of elimination and control of malaria. Therefore, the objective of this study was to assess research trend on insecticide resistance of Anopheles mosquito. In specific, number of publications, countries, institutions, and authors’ research profile, citation analysis, international collaborations, and impact of journals publishing documents on insecticide resistance will be presented. It was conducted via Scopus search engine which was used to retrieve relevant data. Keywords used were based on literature available on this topic. The duration of study was set from 1996–2015. RESULTS: A total of 616 documents, mainly as original research articles (n = 569; 92.37%) were retrieved. The average number of citations per article was 26.36. Poisson log-linear regression analysis indicated that there was a 6.00% increase in the number of publications for each extra article on pyrethroid resistance. A total of 82 different countries and 1922 authors participated in publishing retrieved articles. The United Kingdom (UK) ranked first in number of publications followed by the United States of America (USA) and France. The top ten productive countries included seven African countries. The UK had collaborations mostly with Benin (relative link strength = 46). A total of 1817 institution/ organizations participated in the publication of retrieved articles. The most active institution/ organization was Liverpool School of Tropical Medicine. Retrieved articles were published in 134 different scientific peer reviewed journals. The journal that published most on this topic was Malaria Journal (n = 101; 16.4%). Four of the top active authors were from South Africa and two were from the UK. Three of the top ten cited articles were published in Insect Molecular Biology journal. Six articles were about pyrethroid resistance and at least two were about DDT resistance. CONCLUSION: Publications on insecticide resistance in malaria vector has gained momentum in the past decade. International collaborations enhanced the knowledge about the situation of vector resistance in countries with endemic malaria. Molecular biology of insecticide resistance is the key issue in understanding and overcoming this emerging problems.",2016 Nov 25,"['Sweileh, Waleed M.', 'Sawalha, Ansam F.', 'Al-Jabi, Samah W.', 'Zyoud, Sa’ed H.', 'Shraim, Naser Y.', 'Abu-Taha, Adham S.']",Global Health,,,True
1ef187d95b5c98c9ef187f3b5cf23e276bf1b018,PMC,Detection and phylogenetic analysis of porcine epidemic diarrhea virus in central China based on the ORF3 gene and the S1 gene,http://dx.doi.org/10.1186/s12985-016-0646-8,PMC5123408,27887624,CC BY,"BACKGROUND: Porcine epidemic diarrhea (PED) has increased in severity in China since 2010. To investigate further the infectivity, genetic diversity and molecular epidemiology of its causative agent, the porcine epidemic diarrhea virus (PEDV), we assessed 129 clinical samples, which were the intestinal tissue of piglets with severe diarrhea, from 17 cities in central China. Both the spike (S) glycoprotein (S1, 1–789 amino acids (aa)) and the full-length ORF3 gene of 21 representative field strains from 21 farms in 11 cities were sequenced and analysed. METHODS: PEDV was detected by reverse transcription-polymerase chain reaction (RT-PCR), and S1 and ORF3 sequences were processed by the Clustal W method via DNAMAN 8 software, and phylogenetic trees were constructed by the neighbor-joining method using MEGA 6 software. RESULTS: The prevalence of PEDV was 92.25% and was detected in 119 of 129 samples, with 94.03% (63 of 67) of pig farms harbouring the disease. According to the phylogenetic analysis of the S1 genes, our isolates all fell into group G2 (variants) and showed a close relationship to isolates from Chinese (HN1303, CH/ZMDZY/11 and AJ1102), Korean (AD01), American (MN, IA1, IA2 and 13–019349) sources, and these isolates differed genetically from other Chinese (LZC, CH/HNZZ/2011 and SD-M) and Korean (SM98) strains as well Japanese (83-P5 and MK) strains. In addition, our isolates differed from attenuated vaccine strains, CV777 (used in China) and DR13 (used in Korea). According to our derived amino acid sequence analysis, we detected one novel variant PEDV, viz: CH/HNLY, with 4-aa insertion/deletion (RSSS/T) at position 375 and 1-aa (D) deletion at position 430 compared to the CV777 attenuated strain. These mutations were located on the receptor binding domain. Our ORF3 gene analyses showed that the prevalent PEDV isolates were variants, and the isolated strains differed genetically from the vaccine strains. CONCLUSIONS: These findings illustrated the existence of genetic diversity among geographically distinct PEDV strains, and our study has provided an impetus to conduct further research on the PEDV receptor binding protein and on the new and efficacious vaccines design. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0646-8) contains supplementary material, which is available to authorized users.",2016 Nov 25,"['Su, Yunfang', 'Liu, Yunchao', 'Chen, Yumei', 'Zhao, Baolei', 'Ji, Pengchao', 'Xing, Guangxu', 'Jiang, Dawei', 'Liu, Chang', 'Song, Yapeng', 'Wang, Guoqiang', 'Li, Dongliang', 'Deng, Ruiguang', 'Zhang, Gaiping']",Virol J,,,True
c7d52191db94d11ad1d56bb48ecc64656b44a613,PMC,"In the eye of the beholder: to make global health estimates useful, make them more socially robust",http://dx.doi.org/10.3402/gha.v9.32298,PMC5124117,28532303,CC BY,"A plethora of new development goals and funding institutions have greatly increased the demand for internationally comparable health estimates in recent years, and have brought important new players into the field of health estimate production. These changes have rekindled debates about the validity and legitimacy of global health estimates. This paper draws on country case studies and personal experience to support our opinion that the production and use of estimates are deeply embedded in specific social, economic, political and ideational contexts, which differ at different levels of the global health architecture. Broadly, most global health estimates tend to be made far from the local contexts in which the data upon which they are based are collected, and where the results of estimation processes must ultimately be used if they are to make a difference to the health of individuals. Internationally standardised indicators are necessary, but they are no substitute for data that meet local needs, and that fit with local ideas of what is credible and useful. In other words, data that are both technically and socially robust for those who make key decisions about health. We suggest that greater engagement of local actors (and local data) in the formulation, communication and interpretation of health estimates would increase the likelihood that these data will be used by those most able to translate them into health gains for the longer term. Besides strengthening national information systems, this requires ongoing interaction, building trust and establishing a communicative infrastructure. Local capacities to use knowledge to improve health must be supported.",2017 May 22,"['Pisani, Elizabeth', 'Kok, Maarten']",Glob Health Action,,,True
dd94afcee3d0c4dbc80b40435ff4fb65487af3b6,PMC,The performance of interferon-gamma release assay in nontuberculous mycobacterial diseases: a retrospective study in China,http://dx.doi.org/10.1186/s12890-016-0320-3,PMC5124224,27887611,CC BY,"BACKGROUND: The interferon-gamma release assay (IGRA) is more specific than the tuberculin skin test to discriminate between tuberculosis (TB) and nontuberculous mycobacterial (NTM) diseases. Here we performed a retrospective study to evaluate the performance of the T-SPOT.TB in patients with NTM diseases. METHODS: Between March, 2013 and Nov, 2015, a total of 58 patients with NTM diseases had a T-SPOT.TB performed were enrolled, 30 patients had definite NTM diseases, 28 had probable diseases. Their clinicopathological characteristics were reviewed and analyzed. Cultures for mycobacteria were performed. The indirect proportion method with Löwenstein–Jensen (L-J) medium was used for first-line drug susceptibility test. T-SPOT.TB assay was performed according to the manufacturer’s instructions. Data were expressed as mean ± standard deviation (continuous variables) and as numbers and percentages (categorical variables). The χ (2) test was used for comparisons between proportions. RESULTS: The average age was 51.8 ± 16.1 years (range 10 to 77 years), 58.6% (34/58) were male. 16.4% (9/55) were TB-PCR positive. 34 (58.6%) isolates were Mycobacterium intracellulare, ten (17.2%) were Mycobacterium chelonae and seven (12.1%) were Mycobacterium fortuitum. Fifty-two (89.7%) patients were NTM lung disease, five (8.6%) were pleural disease, and one (1.7%) lymphadenitis. The total positivity of T-SPOT.TB was 53.4% (31/58) among the whole group (probable and definite). For probable cases, the T-SPOT.TB assay was positive in 53.5% (15/28); for definite cases, 16 (53.3%) of 30 definite cases were positive. There was no statistical difference in the positivity rate between them (P < 0.01). CONCLUSIONS: In the study, we showed that a significant portion of NTM diseases were T-SPOT.TB positive in China. Although T-SPOT.TB is useful diagnostic method for differentiating TB from NTM diseases, in China, the IGRA assay show limited value in the discrimination. In addition, further research is needed to investigate the association between TB infection and treatment for NTM patients.",2016 Nov 25,"['Wang, Mao-Shui', 'Wang, Jun-Li', 'Wang, Xin-Feng']",BMC Pulm Med,,,True
48aba0f18c129840aeb900f176b1f40de0b598a4,PMC,Sensitization with vaccinia virus encoding H5N1 hemagglutinin restores immune potential against H5N1 influenza virus,http://dx.doi.org/10.1038/srep37915,PMC5124960,27892498,CC BY,"H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated mortality compared with seasonal influenza viruses like H1N1 pandemic influenza (H1N1 pdm) virus. We identified a mechanism associated with the severe symptoms seen with H5N1 HPAI virus infection. H5N1 HPAI virus infection induced a decrease of dendritic cell number in the splenic extrafollicular T-cell zone and impaired formation of the outer layers of B-cell follicles, resulting in insufficient levels of antibody production after infection. However, in animals vaccinated with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and efficient antibody production. These results indicate that a recombinant vaccinia encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can be a useful vaccine candidate.",2016 Nov 28,"['Yasui, Fumihiko', 'Itoh, Yasushi', 'Ikejiri, Ai', 'Kitabatake, Masahiro', 'Sakaguchi, Nobuo', 'Munekata, Keisuke', 'Shichinohe, Shintaro', 'Hayashi, Yukiko', 'Ishigaki, Hirohito', 'Nakayama, Misako', 'Sakoda, Yoshihiro', 'Kida, Hiroshi', 'Ogasawara, Kazumasa', 'Kohara, Michinori']",Sci Rep,,,True
6288976f9f6047712e54ceada28a66fdeed771ab,PMC,Sensitization with vaccinia virus encoding H5N1 hemagglutinin restores immune potential against H5N1 influenza virus,http://dx.doi.org/10.1038/srep37915,PMC5124960,27892498,CC BY,"H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated mortality compared with seasonal influenza viruses like H1N1 pandemic influenza (H1N1 pdm) virus. We identified a mechanism associated with the severe symptoms seen with H5N1 HPAI virus infection. H5N1 HPAI virus infection induced a decrease of dendritic cell number in the splenic extrafollicular T-cell zone and impaired formation of the outer layers of B-cell follicles, resulting in insufficient levels of antibody production after infection. However, in animals vaccinated with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and efficient antibody production. These results indicate that a recombinant vaccinia encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can be a useful vaccine candidate.",2016 Nov 28,"['Yasui, Fumihiko', 'Itoh, Yasushi', 'Ikejiri, Ai', 'Kitabatake, Masahiro', 'Sakaguchi, Nobuo', 'Munekata, Keisuke', 'Shichinohe, Shintaro', 'Hayashi, Yukiko', 'Ishigaki, Hirohito', 'Nakayama, Misako', 'Sakoda, Yoshihiro', 'Kida, Hiroshi', 'Ogasawara, Kazumasa', 'Kohara, Michinori']",Sci Rep,,,False
ddfd6e95ebc735146d0f0d6ea7faacaf99d9613c,PMC,SARS-CoV fusion peptides induce membrane surface ordering and curvature,http://dx.doi.org/10.1038/srep37131,PMC5125003,27892522,CC BY,"Viral membrane fusion is an orchestrated process triggered by membrane-anchored viral fusion glycoproteins. The S2 subunit of the spike glycoprotein from severe acute respiratory syndrome (SARS) coronavirus (CoV) contains internal domains called fusion peptides (FP) that play essential roles in virus entry. Although membrane fusion has been broadly studied, there are still major gaps in the molecular details of lipid rearrangements in the bilayer during fusion peptide-membrane interactions. Here we employed differential scanning calorimetry (DSC) and electron spin resonance (ESR) to gather information on the membrane fusion mechanism promoted by two putative SARS FPs. DSC data showed the peptides strongly perturb the structural integrity of anionic vesicles and support the hypothesis that the peptides generate opposing curvature stresses on phosphatidylethanolamine membranes. ESR showed that both FPs increase lipid packing and head group ordering as well as reduce the intramembrane water content for anionic membranes. Therefore, bending moment in the bilayer could be generated, promoting negative curvature. The significance of the ordering effect, membrane dehydration, changes in the curvature properties and the possible role of negatively charged phospholipids in helping to overcome the high kinetic barrier involved in the different stages of the SARS-CoV-mediated membrane fusion are discussed.",2016 Nov 28,"['Basso, Luis G. M.', 'Vicente, Eduardo F.', 'Crusca Jr., Edson', 'Cilli, Eduardo M.', 'Costa-Filho, Antonio J.']",Sci Rep,,,True
c182fa44ed42d3f4bce316dc78bec2ea3b6d31ba,PMC,Analysis of Synonymous Codon Usage Bias of Zika Virus and Its Adaption to the Hosts,http://dx.doi.org/10.1371/journal.pone.0166260,PMC5125587,27893824,CC BY,"Zika virus (ZIKV) is a mosquito-borne virus (arbovirus) in the family Flaviviridae, and the symptoms caused by ZIKV infection in humans include rash, fever, arthralgia, myalgia, asthenia and conjunctivitis. Codon usage bias analysis can reveal much about the molecular evolution and host adaption of ZIKV. To gain insight into the evolutionary characteristics of ZIKV, we performed a comprehensive analysis on the codon usage pattern in 46 ZIKV strains by calculating the effective number of codons (ENc), codon adaptation index (CAI), relative synonymous codon usage (RSCU), and other indicators. The results indicate that the codon usage bias of ZIKV is relatively low. Several lines of evidence support the hypothesis that translational selection plays a role in shaping the codon usage pattern of ZIKV. The results from a correspondence analysis (CA) indicate that other factors, such as base composition, aromaticity, and hydrophobicity may also be involved in shaping the codon usage pattern of ZIKV. Additionally, the results from a comparative analysis of RSCU between ZIKV and its hosts suggest that ZIKV tends to evolve codon usage patterns that are comparable to those of its hosts. Moreover, selection pressure from Homo sapiens on the ZIKV RSCU patterns was found to be dominant compared with that from Aedes aegypti and Aedes albopictus. Taken together, both natural translational selection and mutation pressure are important for shaping the codon usage pattern of ZIKV. Our findings contribute to understanding the evolution of ZIKV and its adaption to its hosts.",2016 Nov 28,"['Wang, Hongju', 'Liu, Siqing', 'Zhang, Bo', 'Wei, Wenqiang']",PLoS One,,,True
1fddc1d4d4d31015df5e948d0119947b8bd681d1,PMC,Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection,http://dx.doi.org/10.1371/journal.pone.0167221,PMC5125695,27893810,CC BY,"Influenza A virus (IAV) causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection.",2016 Nov 28,"['Perwitasari, Olivia', 'Johnson, Scott', 'Yan, Xiuzhen', 'Register, Emery', 'Crabtree, Jackelyn', 'Gabbard, Jon', 'Howerth, Elizabeth', 'Shacham, Sharon', 'Carlson, Robert', 'Tamir, Sharon', 'Tripp, Ralph A.']",PLoS One,,,True
fbf232152712b5e379797c6b0008bb7926001bb7,PMC,Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells,http://dx.doi.org/10.1038/srep38115,PMC5126690,27897259,CC BY,"SM934 is an artemisinin analogue with immunosuppressive properties and potent therapeutic activity against lupus-like diseases in autoimmune mice. In this report, the therapeutic efficacy and underlying mechanisms of SM934 on rheumatoid arthritis (RA) was investigated using collagen-induced arthritis (CIA) in DBA/1J mice. We demonstrated that SM934 treatment alleviate the severity of arthritis in CIA mice with established manifestations. The therapeutic benefits were associated with ameliorated joint swelling and reduced extent of bone erosion and destruction. Further, administration of SM934 diminished the development of T follicular helper (Tfh) cells and Th17 cells and suppressed the production of pathogenic antibodies, without altering the proportion of germinal center B cells. Ex vivo, SM934 treatment inhibited the bovine type II collagen (CII) induced proliferation and inflammatory cytokines secretion of CII -reactive T cells. In vitro, SM934 impeded the polarization of naïve CD4(+) T cells into Tfh cells and the expression of its transcript factor Bcl-6. Moreover, SM934 decreased the IL-21-producing CD4(+) T cells and dampened the IL-21 downstream signaling through STAT3. These finding offered the convincing evidence that artemisinin derivative might attenuate RA by simultaneously interfering with the generation of Tfh cells and Th17 cells as well as the subsequent antibody-mediated immune responses.",2016 Nov 29,"['Lin, Ze-Min', 'Yang, Xiao-Qian', 'Zhu, Feng-Hua', 'He, Shi-Jun', 'Tang, Wei', 'Zuo, Jian-Ping']",Sci Rep,,,True
b706357b278bc457986d817617d68ea75f10dda7,PMC,Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells,http://dx.doi.org/10.1038/srep38115,PMC5126690,27897259,CC BY,"SM934 is an artemisinin analogue with immunosuppressive properties and potent therapeutic activity against lupus-like diseases in autoimmune mice. In this report, the therapeutic efficacy and underlying mechanisms of SM934 on rheumatoid arthritis (RA) was investigated using collagen-induced arthritis (CIA) in DBA/1J mice. We demonstrated that SM934 treatment alleviate the severity of arthritis in CIA mice with established manifestations. The therapeutic benefits were associated with ameliorated joint swelling and reduced extent of bone erosion and destruction. Further, administration of SM934 diminished the development of T follicular helper (Tfh) cells and Th17 cells and suppressed the production of pathogenic antibodies, without altering the proportion of germinal center B cells. Ex vivo, SM934 treatment inhibited the bovine type II collagen (CII) induced proliferation and inflammatory cytokines secretion of CII -reactive T cells. In vitro, SM934 impeded the polarization of naïve CD4(+) T cells into Tfh cells and the expression of its transcript factor Bcl-6. Moreover, SM934 decreased the IL-21-producing CD4(+) T cells and dampened the IL-21 downstream signaling through STAT3. These finding offered the convincing evidence that artemisinin derivative might attenuate RA by simultaneously interfering with the generation of Tfh cells and Th17 cells as well as the subsequent antibody-mediated immune responses.",2016 Nov 29,"['Lin, Ze-Min', 'Yang, Xiao-Qian', 'Zhu, Feng-Hua', 'He, Shi-Jun', 'Tang, Wei', 'Zuo, Jian-Ping']",Sci Rep,,,False
9cda807f855a7d3786031858813d285ab5a81474,PMC,Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells,http://dx.doi.org/10.1038/srep38115,PMC5126690,27897259,CC BY,"SM934 is an artemisinin analogue with immunosuppressive properties and potent therapeutic activity against lupus-like diseases in autoimmune mice. In this report, the therapeutic efficacy and underlying mechanisms of SM934 on rheumatoid arthritis (RA) was investigated using collagen-induced arthritis (CIA) in DBA/1J mice. We demonstrated that SM934 treatment alleviate the severity of arthritis in CIA mice with established manifestations. The therapeutic benefits were associated with ameliorated joint swelling and reduced extent of bone erosion and destruction. Further, administration of SM934 diminished the development of T follicular helper (Tfh) cells and Th17 cells and suppressed the production of pathogenic antibodies, without altering the proportion of germinal center B cells. Ex vivo, SM934 treatment inhibited the bovine type II collagen (CII) induced proliferation and inflammatory cytokines secretion of CII -reactive T cells. In vitro, SM934 impeded the polarization of naïve CD4(+) T cells into Tfh cells and the expression of its transcript factor Bcl-6. Moreover, SM934 decreased the IL-21-producing CD4(+) T cells and dampened the IL-21 downstream signaling through STAT3. These finding offered the convincing evidence that artemisinin derivative might attenuate RA by simultaneously interfering with the generation of Tfh cells and Th17 cells as well as the subsequent antibody-mediated immune responses.",2016 Nov 29,"['Lin, Ze-Min', 'Yang, Xiao-Qian', 'Zhu, Feng-Hua', 'He, Shi-Jun', 'Tang, Wei', 'Zuo, Jian-Ping']",Sci Rep,,,False
38b50147abf86a5818c6bb5e09b1f07edf51352b,PMC,Antiviral Screening of Multiple Compounds against Ebola Virus,http://dx.doi.org/10.3390/v8110277,PMC5127007,27801778,CC BY,"In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine). A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna). The three most promising compounds (17-DMAG; BGB324; and NCK-8) were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.",2016 Oct 27,"['Dowall, Stuart D.', 'Bewley, Kevin', 'Watson, Robert J.', 'Vasan, Seshadri S.', 'Ghosh, Chandradhish', 'Konai, Mohini M.', 'Gausdal, Gro', 'Lorens, James B.', 'Long, Jason', 'Barclay, Wendy', 'Garcia-Dorival, Isabel', 'Hiscox, Julian', 'Bosworth, Andrew', 'Taylor, Irene', 'Easterbrook, Linda', 'Pitman, James', 'Summers, Sian', 'Chan-Pensley, Jenny', 'Funnell, Simon', 'Vipond, Julia', 'Charlton, Sue', 'Haldar, Jayanta', 'Hewson, Roger', 'Carroll, Miles W.']",Viruses,,,True
4abc50cfc81265083d4cb2aed0a493bb704d0b5b,PMC,Rabies Control and Treatment: From Prophylaxis to Strategies with Curative Potential,http://dx.doi.org/10.3390/v8110279,PMC5127009,27801824,CC BY,"Rabies is an acute, fatal, neurological disease that affects almost all kinds of mammals. Vaccination (using an inactivated rabies vaccine), combined with administration of rabies immune globulin, is the only approved, effective method for post-exposure prophylaxis against rabies in humans. In the search for novel rabies control and treatment strategies, live-attenuated viruses have recently emerged as a practical and promising approach for immunizing and controlling rabies. Unlike the conventional, inactivated rabies vaccine, live-attenuated viruses are genetically modified viruses that are able to replicate in an inoculated recipient without causing adverse effects, while still eliciting robust and effective immune responses against rabies virus infection. A number of viruses with an intrinsic capacity that could be used as putative candidates for live-attenuated rabies vaccine have been intensively evaluated for therapeutic purposes. Additional novel strategies, such as a monoclonal antibody-based approach, nucleic acid-based vaccines, or small interfering RNAs (siRNAs) interfering with virus replication, could further add to the arena of strategies to combat rabies. In this review, we highlight current advances in rabies therapy and discuss the role that they might have in the future of rabies treatment. Given the pronounced and complex impact of rabies on a patient, a combination of these novel modalities has the potential to achieve maximal anti-rabies efficacy, or may even have promising curative effects in the future. However, several hurdles regarding clinical safety considerations and public awareness should be overcome before these approaches can ultimately become clinically relevant therapies.",2016 Oct 28,"['Zhu, Shimao', 'Guo, Caiping']",Viruses,,,True
bf2609459ed9b514ad4b6ee4b0eb3656c0d6542d,PMC,The Importance of Physiologically Relevant Cell Lines for Studying Virus–Host Interactions,http://dx.doi.org/10.3390/v8110297,PMC5127011,27809273,CC BY,"Viruses interact intimately with the host cell at nearly every stage of replication, and the cell model that is chosen to study virus infection is critically important. Although primary cells reflect the phenotype of healthy cells in vivo better than cell lines, their limited lifespan makes experimental manipulation challenging. However, many tumor-derived and artificially immortalized cell lines have defects in induction of interferon-stimulated genes and other antiviral defenses. These defects can affect virus replication, especially when cells are infected at lower, more physiologically relevant, multiplicities of infection. Understanding the selective pressures and mechanisms underlying the loss of innate signaling pathways is helpful to choose immortalized cell lines without impaired antiviral defense. We describe the trials and tribulations we encountered while searching for an immortalized cell line with intact innate signaling, and how directed immortalization of primary cells avoids many of the pitfalls of spontaneous immortalization.",2016 Nov 1,"['Hare, David', 'Collins, Susan', 'Cuddington, Breanne', 'Mossman, Karen']",Viruses,,,True
ae918e83ef815351c2c0e47a337ec78954f5cec0,PMC,The European Classical Swine Fever Virus Database: Blueprint for a Pathogen-Specific Sequence Database with Integrated Sequence Analysis Tools,http://dx.doi.org/10.3390/v8110302,PMC5127016,27827988,CC BY,"Molecular epidemiology has become an indispensable tool in the diagnosis of diseases and in tracing the infection routes of pathogens. Due to advances in conventional sequencing and the development of high throughput technologies, the field of sequence determination is in the process of being revolutionized. Platforms for sharing sequence information and providing standardized tools for phylogenetic analyses are becoming increasingly important. The database (DB) of the European Union (EU) and World Organisation for Animal Health (OIE) Reference Laboratory for classical swine fever offers one of the world’s largest semi-public virus-specific sequence collections combined with a module for phylogenetic analysis. The classical swine fever (CSF) DB (CSF-DB) became a valuable tool for supporting diagnosis and epidemiological investigations of this highly contagious disease in pigs with high socio-economic impacts worldwide. The DB has been re-designed and now allows for the storage and analysis of traditionally used, well established genomic regions and of larger genomic regions including complete viral genomes. We present an application example for the analysis of highly similar viral sequences obtained in an endemic disease situation and introduce the new geographic “CSF Maps” tool. The concept of this standardized and easy-to-use DB with an integrated genetic typing module is suited to serve as a blueprint for similar platforms for other human or animal viruses.",2016 Nov 7,"['Postel, Alexander', 'Schmeiser, Stefanie', 'Zimmermann, Bernd', 'Becher, Paul']",Viruses,,,True
d2d8597279c4e4503fbe1c11365fd154230add81,PMC,Three-Dimensional Rotating Wall Vessel-Derived Cell Culture Models for Studying Virus-Host Interactions,http://dx.doi.org/10.3390/v8110304,PMC5127018,27834891,CC BY,"The key to better understanding complex virus-host interactions is the utilization of robust three-dimensional (3D) human cell cultures that effectively recapitulate native tissue architecture and model the microenvironment. A lack of physiologically-relevant animal models for many viruses has limited the elucidation of factors that influence viral pathogenesis and of complex host immune mechanisms. Conventional monolayer cell cultures may support viral infection, but are unable to form the tissue structures and complex microenvironments that mimic host physiology and, therefore, limiting their translational utility. The rotating wall vessel (RWV) bioreactor was designed by the National Aeronautics and Space Administration (NASA) to model microgravity and was later found to more accurately reproduce features of human tissue in vivo. Cells grown in RWV bioreactors develop in a low fluid-shear environment, which enables cells to form complex 3D tissue-like aggregates. A wide variety of human tissues (from neuronal to vaginal tissue) have been grown in RWV bioreactors and have been shown to support productive viral infection and physiological meaningful host responses. The in vivo-like characteristics and cellular features of the human 3D RWV-derived aggregates make them ideal model systems to effectively recapitulate pathophysiology and host responses necessary to conduct rigorous basic science, preclinical and translational studies.",2016 Nov 9,"['Gardner, Jameson K.', 'Herbst-Kralovetz, Melissa M.']",Viruses,,,True
450c84277f6e9475368ad36719ef5d7b6595b514,PMC,Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its Further Development as a Microbicide Targeting HIV-1 and Other Enveloped Viruses,http://dx.doi.org/10.3390/v8110311,PMC5127025,27869695,CC BY,"Griffithsin (GRFT), a lectin from Griffithsia species, inhibits human immunodeficiency virus-1 (HIV-1) replication at sub-nanomolar concentrations, with limited cellular toxicity. However, in vivo safety of GRFT is not fully understood, especially following parenteral administration. We first assessed GRFT’s effects in vitro, on mouse peripheral blood mononuclear cell (mPBMC) viability, mitogenicity, and activation using flow-cytometry, as well as cytokine secretion through enzyme-linked immunosorbent assay (ELISA). Toxicological properties of GRFT were determined after a single subcutaneous administration of 50 mg/kg or 14 daily doses of 10 mg/kg in BALB/c mice. In the context of microbicide development, toxicity of GRFT at 2 mg/kg was determined after subcutaneous, intravaginal, and intraperitoneal administrations, respectively. Interestingly, GRFT caused no significant cell death, mitogenicity, activation, or cytokine release in mPBMCs, validating the usefulness of a mouse model. An excellent safety profile for GRFT was obtained in vivo: no overt changes were observed in animal fitness, blood chemistry or CBC parameters. Following GRFT treatment, reversible splenomegaly was observed with activation of certain spleen B and T cells. However, spleen tissues were not pathologically altered by GRFT (either with a single high dose or chronic doses). Finally, no detectable toxicity was found after mucosal or systemic treatment with 2 mg/kg GRFT, which should be further developed as a microbicide for HIV prevention.",2016 Nov 17,"['Kouokam, Joseph Calvin', 'Lasnik, Amanda B.', 'Palmer, Kenneth E.']",Viruses,,,True
cc162db1b7050ca10b6b99bf2857185777acb67b,PMC,Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its Further Development as a Microbicide Targeting HIV-1 and Other Enveloped Viruses,http://dx.doi.org/10.3390/v8110311,PMC5127025,27869695,CC BY,"Griffithsin (GRFT), a lectin from Griffithsia species, inhibits human immunodeficiency virus-1 (HIV-1) replication at sub-nanomolar concentrations, with limited cellular toxicity. However, in vivo safety of GRFT is not fully understood, especially following parenteral administration. We first assessed GRFT’s effects in vitro, on mouse peripheral blood mononuclear cell (mPBMC) viability, mitogenicity, and activation using flow-cytometry, as well as cytokine secretion through enzyme-linked immunosorbent assay (ELISA). Toxicological properties of GRFT were determined after a single subcutaneous administration of 50 mg/kg or 14 daily doses of 10 mg/kg in BALB/c mice. In the context of microbicide development, toxicity of GRFT at 2 mg/kg was determined after subcutaneous, intravaginal, and intraperitoneal administrations, respectively. Interestingly, GRFT caused no significant cell death, mitogenicity, activation, or cytokine release in mPBMCs, validating the usefulness of a mouse model. An excellent safety profile for GRFT was obtained in vivo: no overt changes were observed in animal fitness, blood chemistry or CBC parameters. Following GRFT treatment, reversible splenomegaly was observed with activation of certain spleen B and T cells. However, spleen tissues were not pathologically altered by GRFT (either with a single high dose or chronic doses). Finally, no detectable toxicity was found after mucosal or systemic treatment with 2 mg/kg GRFT, which should be further developed as a microbicide for HIV prevention.",2016 Nov 17,"['Kouokam, Joseph Calvin', 'Lasnik, Amanda B.', 'Palmer, Kenneth E.']",Viruses,,,False
dbd7344969972f79b75ee7553487633e645d9a3b,PMC,Towards Equity in Health: Researchers Take Stock,http://dx.doi.org/10.1371/journal.pmed.1002186,PMC5127492,27898673,CC0,"For the 2016 end-of-the-year editorial, the PLOS Medicine editors asked 7 global health leaders to discuss developments relevant to the equitable provision of medical care to all populations. The result is a collection of expert views on ethical trial design, research during outbreaks, high-burden infectious diseases, diversity in research and protection of migrants.",2016 Nov 29,"[None, 'Rid, Annette', 'Johansson, Michael A.', 'Leung, Gabriel', 'Valantine, Hannah', 'Burchard, Esteban G.', 'Oh, Sam S.', 'Zimmerman, Cathy']",PLoS Med,,,True
89444dffc7f46f0f52709e43550ddb363a720340,PMC,Analysis of chikungunya virus proteins reveals that non-structural proteins nsP2 and nsP3 exhibit RNA interference (RNAi) suppressor activity,http://dx.doi.org/10.1038/srep38065,PMC5128919,27901124,CC BY,"RNAi pathway is an antiviral defence mechanism employed by insects that result in degradation of viral RNA thereby curbing infection. Several viruses including flaviviruses encode viral suppressors of RNAi (VSRs) to counteract the antiviral RNAi pathway. Till date, no VSR has been reported in alphaviruses. The present study was undertaken to evaluate chikungunya virus (CHIKV) proteins for RNAi suppressor activity. We systematically analyzed all nine CHIKV proteins for RNAi suppressor activity using Sf21 RNAi sensor cell line based assay. Two non-structural proteins, namely, nsP2 and nsP3 were found to exhibit RNAi suppressor activity. We further validated the findings in natural hosts, namely in Aedes and in mammalian cell lines and further through EMSA and Agrobacterium infiltration in GFP silenced transgenic tobacco plants. Domains responsible for maximum RNAi suppressor activity were also identified within these proteins. RNA binding motifs in these domains were identified and their participation in RNAi suppression evaluated using site directed mutagenesis. Sequence alignment of these motifs across all species of known alphaviruses revealed conservation of these motifs emphasizing on a similar role of action in other species of alphaviruses as well. Further validation of RNAi suppressor activity of these proteins awaits establishment of specific virus infection models.",2016 Nov 30,"['Mathur, Kalika', 'Anand, Abhishek', 'Dubey, Sunil Kumar', 'Sanan-Mishra, Neeti', 'Bhatnagar, Raj K.', 'Sunil, Sujatha']",Sci Rep,,,True
64bdff3b452cc5f83921b0e3811d4be1cf1af3cf,PMC,Analysis of chikungunya virus proteins reveals that non-structural proteins nsP2 and nsP3 exhibit RNA interference (RNAi) suppressor activity,http://dx.doi.org/10.1038/srep38065,PMC5128919,27901124,CC BY,"RNAi pathway is an antiviral defence mechanism employed by insects that result in degradation of viral RNA thereby curbing infection. Several viruses including flaviviruses encode viral suppressors of RNAi (VSRs) to counteract the antiviral RNAi pathway. Till date, no VSR has been reported in alphaviruses. The present study was undertaken to evaluate chikungunya virus (CHIKV) proteins for RNAi suppressor activity. We systematically analyzed all nine CHIKV proteins for RNAi suppressor activity using Sf21 RNAi sensor cell line based assay. Two non-structural proteins, namely, nsP2 and nsP3 were found to exhibit RNAi suppressor activity. We further validated the findings in natural hosts, namely in Aedes and in mammalian cell lines and further through EMSA and Agrobacterium infiltration in GFP silenced transgenic tobacco plants. Domains responsible for maximum RNAi suppressor activity were also identified within these proteins. RNA binding motifs in these domains were identified and their participation in RNAi suppression evaluated using site directed mutagenesis. Sequence alignment of these motifs across all species of known alphaviruses revealed conservation of these motifs emphasizing on a similar role of action in other species of alphaviruses as well. Further validation of RNAi suppressor activity of these proteins awaits establishment of specific virus infection models.",2016 Nov 30,"['Mathur, Kalika', 'Anand, Abhishek', 'Dubey, Sunil Kumar', 'Sanan-Mishra, Neeti', 'Bhatnagar, Raj K.', 'Sunil, Sujatha']",Sci Rep,,,False
59e5392ae9728ae529623e00c6d2e411a931fffc,PMC,Having a usual source of care and its associated factors in Korean adults: a cross-sectional study of the 2012 Korea Health Panel Survey,http://dx.doi.org/10.1186/s12875-016-0555-3,PMC5129206,27899071,CC BY,"BACKGROUND: Usual source of care (USC) is one of the hallmarks of primary care. We aimed to examine the status of having a USC and its patient-related sociodemographic factors among Korean adults. METHODS: Data were obtained from the 2012 Korea Health Panel survey. Panel participants were selected for the study who were aged 18 years or older and who replied to questionnaire items on having a USC (n = 11,935). RESULTS: Of the participants, 21.5% had a usual place and 13.9% had a usual physician. Reasons for not having a USC were seldom being ill (66.1%), the preference to visit multiple medical institutions (27.9%), and others. The private community clinic was the most common type of usual place (57.0%). In patient-reported attributes of care provided by a usual physician, the percentages of positive responses for comprehensiveness and coordination were 67.2% and 34.5%, respectively. By institution type, primary care clinics showed the lowest percentage (32.8%) of positive responses for coordination. Adjusted odds ratios of having a usual physician were 3.77 (95% confidence interval, CI: 3.75–3.79) for those aged 65 years or older (vs. aged 18–34 years), 1.31 (CI: 1.30–1.31) for females (vs. males), 0.72 (CI: 0.72–0.73) for unmarried people (vs. married), 1.16 (CI: 1.16–1.16) for college graduates or higher (vs. elementary school graduate or less), 0.64 for the fifth quintile (vs. the first quintile) by household income, 1.53 (CI: 1.52–1.54) for Medical Aid (vs. employee health insurance) for type of health insurance, and 4.09 (CI: 4.08–4.10) for presence (vs. absence) of a chronic diseases. CONCLUSIONS: The proportion of Korean adults who have a USC is extremely low, the most influential factor of having a USC is having a chronic disease or not, and Korean patients experience much poorer health care coordination than do patients in other industrialized countries. The findings of this study will give insight to researchers and policy makers regarding the potential facilitators of and barriers to promoting having a USC in the general Korean public.",2016 Nov 29,"['An, Ah Reum', 'Kim, Kyoungwoo', 'Lee, Jae-Ho', 'Sung, Nak-Jin', 'Lee, Sang-il', 'Hyun, Min Kyung']",BMC Fam Pract,,,True
7729f9d0b2d49fd43519f42d2637a55b03e1c778,PMC,Multiple molecular detection of respiratory viruses and associated signs of airway inflammation in racehorses,http://dx.doi.org/10.1186/s12985-016-0657-5,PMC5129218,27899161,CC BY,"BACKGROUND: The potential involvement of viruses in inflammatory airway disease (IAD) was previously investigated through either serology or PCR from nasopharyngeal swabs (NS). The aims of this study were to determine the prevalence and incidence of viral genome detection by qPCR in the equine airways, and their association with respiratory clinical signs. METHODS: Both NS and tracheal washes (TW) were collected monthly on 52 Standardbred racehorses at training, over 27 consecutive months (581 samples). Equid herpesviruses (EHV)-1, −4, −2 and −5, equine rhinitis virus-A and -B (ERBV), equine adenovirus-1 and −2, equine coronavirus and equine influenza virus were systematically investigated in both NS and TW. Nasal discharge, coughing, tracheal mucus score and TW neutrophil proportions were simultaneously recorded. RESULTS: Genome for 7/10 viruses were detected at least once throughout the study; up to 4 different viruses being also concomitantly detected. Monthly incidence in TW was respectively 27.9% (EHV-5), 24.8% (EHV-2), 7.1% (ERBV), 3.8% (EHV-4), 1.9% (EAdV1) and 0.2% (EHV-1; ERAV). Neither agreement nor correlation between NS and TW was found for respectively genome detection and viral loads. Detection of viral genome in NS was not associated with any clinical sign. Coughing was significantly associated with TW detection of EHV-2 DNA (OR 3.1; P = 0.01) and ERBV RNA (OR 5.3; P < 0.001). Detection of EHV-2 DNA in TW was also significantly associated with excess tracheal mucus (OR 2.1; P = 0.02). CONCLUSIONS: Detection and quantification of EHV-2 and ERBV by qPCR in TW, but not in NS, should be considered when investigating horses with IAD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0657-5) contains supplementary material, which is available to authorized users.",2016 Nov 29,"['Doubli-Bounoua, Nadia', 'Richard, Eric A.', 'Léon, Albertine', 'Pitel, Pierre-Hugues', 'Pronost, Stéphane', 'Fortier, Guillaume']",Virol J,,,True
9c8a35cb4e5844ead3ef3214b059ba238cd70362,PMC,Bibliometric analysis of publications on Campylobacter: (2000–2015),http://dx.doi.org/10.1186/s41043-016-0076-7,PMC5129233,27899145,CC BY,"BACKGROUND: Campylobacter species are widespread zoonotic pathogens. Campylobacter jejuni causes a form of gastroenteritis called campylobacteriosis. Campylobacter drug resistance is considered a serious threat. In order to better understand national and international research output on Campylobacter, we conducted this bibliometric overview of publications on Campylobacter. This study can be used to assess extent of interaction and response of researchers, food regulators, and health policy makers to global burden of campylobacateriosis. METHODS: Scopus database was used to retrieve publications with the following keywords (Campylobacter/campylobacteriosis, C. jejuni, C. coli). The study period was set from 2000 to 2015. All types of journal documents, excluding errata, were considered. Bibliometric indicators such as annual growth of publications, country contribution, international collaboration, and citation analysis were presented. The quality of retrieved data was indirectly assessed by Hirsch index and impact factor of journals. RESULTS: A total of 5522 documents were retrieved with median (Q1–Q3) citations of 9 (2–23) and h-index of 113. Annual number of publications showed a fluctuating increase. The core leading journals were Applied and Environmental Microbiology journal and Journal of Food Protection with 246 (4.46%) publications for each. The USA (1309; 23.6%) was the most productive country while Danmarks Tekniske Universitet (150; 2.7%) was the most productive institution. Half of the top ten productive countries were European. France had the lowest percentage (33.5%) of articles with international collaboration while Netherlands (57.7%) had the highest percentage of articles with international collaboration. Approximately half (50.1%) of retrieved articles were published in journals under the subject area of “immunology/microbiology”. Main themes in highly cited articles were molecular biology/genetics and public health burden of campylobacteriosis. There were 728 (13.1%) articles on campylobacter-related drug resistance, and the top cited articles focused mainly on increasing resistance to quinolones and fluoroquinolones. CONCLUSIONS: There was a clear increase in number of publications on Campylobacter. Rational use of antimicrobials in humans, poultry, and animals is highly recommended. International collaboration is highly required particularly in implementing new diagnostic screening technologies to minimize global health burden of Campylobacter and ensure food safety.",2016 Nov 29,"['Sweileh, Waleed M.', 'Al-Jabi, Samah W.', 'Sawalha, Ansam F.', 'AbuTaha, Adham S.', 'Zyoud, Sa’ed H.']",J Health Popul Nutr,,,True
aa96296a83b9395223f9a9b1b116f50ae8bcdb11,PMC,Relationship between hospital ward design and healthcare-associated infection rates: a systematic review and meta-analysis,http://dx.doi.org/10.1186/s13756-016-0152-1,PMC5129243,27957323,CC BY,"BACKGROUND: The influence of the hospital’s infrastructure on healthcare-associated colonization and infection rates has thus far infrequently been examined. In this review we examine whether healthcare facility design is a contributing factor to multifaceted infection control strategies. METHODS: We searched PubMed/MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) from 1990 to December 31(st), 2015, with language restriction to English, Spanish, German and French. RESULTS: We identified three studies investigating accessibility of the location of the antiseptic hand rub dispenser. Each of them showed a significant improvement of hand hygiene compliance or agent consumption with the implementation of accessible dispensers near the patient bed. Nine eligible studies evaluated the impact of single-patient rooms on the acquisition of healthcare-associated colonization and infections in comparison to multi-bedrooms or an open ward design. Six of these studies showed a significant benefit of single-patient bedrooms in reducing the healthcare-associated colonization and infection rate, whereas three studies found that single-patient rooms are neither a protective nor risk factor. In meta-analyses, the overall risk ratio for acquisition of healthcare-associated colonization and infection was 0.55 (95% CI: 0.41 to 0.74), for healthcare-associated colonization 0.52 (95% CI: 0.32 to 0.85) and for bacteremia 0.64 (95% CI: 0.53 to 0.76), all in favor of patient care in single-patient bedrooms. CONCLUSION: Implementation of single-patient rooms and easily accessible hand rub dispensers located near the patient’s bed are beneficial for infection control and are useful parts of a multifaceted strategy for reducing healthcare-associated colonization and infections.",2016 Nov 29,"['Stiller, Andrea', 'Salm, Florian', 'Bischoff, Peter', 'Gastmeier, Petra']",Antimicrob Resist Infect Control,,,True
ca5c35779ac657261ff729dd0f8509e1b14a6acd,PMC,Clinical determinants of the severity of Middle East respiratory syndrome (MERS): a systematic review and meta-analysis,http://dx.doi.org/10.1186/s12889-016-3881-4,PMC5129628,27899100,CC BY,"BACKGROUND: While the risk of severe complications of Middle East respiratory syndrome (MERS) and its determinants have been explored in previous studies, a systematic analysis of published articles with different designs and populations has yet to be conducted. The present study aimed to systematically review the risk of death associated with MERS as well as risk factors for associated complications. METHODS: PubMed and Web of Science databases were searched for clinical and epidemiological studies on confirmed cases of MERS. Eligible articles reported clinical outcomes, especially severe complications or death associated with MERS. Risks of admission to intensive care unit (ICU), mechanical ventilation and death were estimated. Subsequently, potential associations between MERS-associated death and age, sex, underlying medical conditions and study design were explored. RESULTS: A total of 25 eligible articles were identified. The case fatality risk ranged from 14.5 to 100%, with the pooled estimate at 39.1%. The risks of ICU admission and mechanical ventilation ranged from 44.4 to 100% and from 25.0 to 100%, with pooled estimates at 78.2 and 73.0%, respectively. These risks showed a substantial heterogeneity among the identified studies, and appeared to be the highest in case studies focusing on ICU cases. We identified older age, male sex and underlying medical conditions, including diabetes mellitus, renal disease, respiratory disease, heart disease and hypertension, as clinical predictors of death associated with MERS. In ICU case studies, the expected odds ratios (OR) of death among patients with underlying heart disease or renal disease to patients without such comorbidities were 0.6 (95% Confidence Interval (CI): 0.1, 4.3) and 0.6 (95% CI: 0.0, 2.1), respectively, while the ORs were 3.8 (95% CI: 3.4, 4.2) and 2.4 (95% CI: 2.0, 2.9), respectively, in studies with other types of designs. CONCLUSIONS: The heterogeneity for the risk of death and severe manifestations was substantially high among the studies, and varying study designs was one of the underlying reasons for this heterogeneity. A statistical estimation of the risk of MERS death and identification of risk factors must be conducted, particularly considering the study design and potential biases associated with case detection and diagnosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-016-3881-4) contains supplementary material, which is available to authorized users.",2016 Nov 29,"['Matsuyama, Ryota', 'Nishiura, Hiroshi', 'Kutsuna, Satoshi', 'Hayakawa, Kayoko', 'Ohmagari, Norio']",BMC Public Health,,,True
cefbe0e7441f96ec3d0a08e9d7f291dbcf44f4e3,PMC,Interferon α Induces the Apoptosis of Cervical Cancer HeLa Cells by Activating both the Intrinsic Mitochondrial Pathway and Endoplasmic Reticulum Stress-Induced Pathway,http://dx.doi.org/10.3390/ijms17111832,PMC5133833,27827850,CC BY,"The interferon α (IFN-α) has been often used as a sensitizing agent for the treatment of various malignancies such as hepatocellular carcinoma, malignant melanoma, and renal cell cancer by promoting the apoptosis of thesetumor cell types. However, the effect of IFN-α on cervical cancer remains unknown. In this study, HeLa cells were used as a testing model for the treatment of IFN-α on cervical cancer. The results indicate that IFN-α markedly inhibits the proliferation and induces the apoptosis of HeLa cells. The activation of caspase 3, the up-regulation of both Bim and cleaved poly (ADP-ribose) polymerase (PARP) 1, the down-regulation of Bcl-xL, as well as the release of cytochrome c from mitochondria were significantly induced upon IFN-α treatment, indicating that the intrinsic apoptotic pathway could be activated by IFN-α treatment. In addition, caspase 4—which is involved in the endoplasmic reticulum (ER) stress-induced apoptosis—was activated in response to IFN-α treatment. Knocking down caspase 4 by small interfering RNA (siRNA) markedly reduced the IFN-α-mediated cell apoptosis. However, no significant changes in the expressions of caspases 8 and 10 were observed upon IFN-α treatment, indicating that the apoptosis caused by IFN-α might be independent of the extrinsic apoptotic pathway. These findings suggest that IFN-α may possess anti-cervical cancer capacity by activating cell apoptosis via the intrinsic mitochondrial pathway and caspase-4-related ER stress-induced pathway.",2016 Nov 2,"['Shi, Wei-Ye', 'Cao, Cheng', 'Liu, Li']",Int J Mol Sci,,,True
9b5f7347b52c46ad29b1991560e6251bfdfd8df2,PMC,A Melting Curve-Based Multiplex RT-qPCR Assay for Simultaneous Detection of Four Human Coronaviruses,http://dx.doi.org/10.3390/ijms17111880,PMC5133880,27886052,CC BY,"Human coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1 are common respiratory viruses associated with acute respiratory infection. They have a global distribution. Rapid and accurate diagnosis of HCoV infection is important for the management and treatment of hospitalized patients with HCoV infection. Here, we developed a melting curve-based multiplex RT-qPCR assay for simultaneous detection of the four HCoVs. In the assay, SYTO 9 was used to replace SYBR Green I as the fluorescent dye, and GC-modified primers were designed to improve the melting temperature (Tm) of the specific amplicon. The four HCoVs were clearly distinguished by characteristic melting peaks in melting curve analysis. The detection sensitivity of the assay was 3 × 10(2) copies for HCoV-OC43, and 3 × 10(1) copies for HCoV-NL63, HCoV-229E and HCoV-HKU1 per 30 μL reaction. Clinical evaluation and sequencing confirmation demonstrated that the assay was specific and reliable. The assay represents a sensitive and reliable method for diagnosis of HCoV infection in clinical samples.",2016 Nov 23,"['Wan, Zhenzhou', 'Zhang, Ya’nan', 'He, Zhixiang', 'Liu, Jia', 'Lan, Ke', 'Hu, Yihong', 'Zhang, Chiyu']",Int J Mol Sci,,,True
25e089b28ebc09fee5ea9ce51d0c12043fa3834c,PMC,A Melting Curve-Based Multiplex RT-qPCR Assay for Simultaneous Detection of Four Human Coronaviruses,http://dx.doi.org/10.3390/ijms17111880,PMC5133880,27886052,CC BY,"Human coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1 are common respiratory viruses associated with acute respiratory infection. They have a global distribution. Rapid and accurate diagnosis of HCoV infection is important for the management and treatment of hospitalized patients with HCoV infection. Here, we developed a melting curve-based multiplex RT-qPCR assay for simultaneous detection of the four HCoVs. In the assay, SYTO 9 was used to replace SYBR Green I as the fluorescent dye, and GC-modified primers were designed to improve the melting temperature (Tm) of the specific amplicon. The four HCoVs were clearly distinguished by characteristic melting peaks in melting curve analysis. The detection sensitivity of the assay was 3 × 10(2) copies for HCoV-OC43, and 3 × 10(1) copies for HCoV-NL63, HCoV-229E and HCoV-HKU1 per 30 μL reaction. Clinical evaluation and sequencing confirmation demonstrated that the assay was specific and reliable. The assay represents a sensitive and reliable method for diagnosis of HCoV infection in clinical samples.",2016 Nov 23,"['Wan, Zhenzhou', 'Zhang, Ya’nan', 'He, Zhixiang', 'Liu, Jia', 'Lan, Ke', 'Hu, Yihong', 'Zhang, Chiyu']",Int J Mol Sci,,,False
4e687843401f339f6b5e8ae35626d0d0ef0b3e7e,PMC,Financing strategies to improve essential public health equalization and its effects in China,http://dx.doi.org/10.1186/s12939-016-0482-x,PMC5134004,27905941,CC BY,"BACKGROUND: In 2009, China launched a health reform to promote the equalization of national essential public health services package (NEPHSP). The present study aimed to describe the financing strategies and mechanisms to improve access to public health for all, identify the strengths and weaknesses of the different approaches, and showed evidence on equity improvement among different regions. METHODS: We reviewed the relevant literatures and identified 208 articles after screening and quality assessment and conducted six key informants’ interviews. Secondary data on national and local government health expenditures, NEPHSP coverage and health indicators in 2003–2014 were collected, descriptive and equity analyses were used. RESULTS: Before 2009, the government subsidy to primary care institutions (PCIs) were mainly used for basic construction and a small part of personnel expenses. Since 2009, the new funds for NEPHSP have significantly expanded service coverage and population coverage. These funds have been allocated by central, provincial, municipal and county governments at different proportions in China’s tax distribution system. Due to the fiscal transfer payment, the Central Government allocated more subsides to less-developed western regions and all the funds were managed in a specific account. Several types of payment methods have been adopted including capitation, pay for performance (P4P), pay for service items, global budget and public health voucher, to address issues from both the supply and demand sides. The equalization of NEPHSP did well through the establishment of health records, systematic care of children and maternal women, etc. Our data showed that the gap between the eastern, central and western regions narrowed. However the coverage for migrants was still low and performance was needed improving in effectiveness of managing patients with chronic diseases. CONCLUSIONS: The delivery of essential public health services was highly influenced by public fiscal policy, and the implementation of health reform since 2009 has led the public health development towards the right direction. However China still needs to increase the fiscal investments to expand service coverage as well as promote the quality of public health services and equality among regions. Independent scientific monitoring and evaluation are also needed.",2016 Dec 1,"['Yang, Li', 'Sun, Li', 'Wen, Liankui', 'Zhang, Huyang', 'Li, Chenyang', 'Hanson, Kara', 'Fang, Hai']",Int J Equity Health,,,True
8c6ca63f974a55bcab6f773fc9cda85c938b93eb,PMC,Sickle-cell disease in febrile children living in a rural village of Madagascar and association with malaria and respiratory infections,http://dx.doi.org/10.1186/s12878-016-0069-1,PMC5134128,27980789,CC BY,"BACKGROUND: In Madagascar, the last study on sickle cell disease (SCD) was done in the early 1980s. The country is known as endemic for malaria and respiratory infections. The main objective of this study was to estimate the prevalence of SCD; the secondary objective was to evaluate its association with malaria and respiratory infections. METHODS: This is a cross-sectional study which was carried out in a rural village in the south east coast of Madagascar between May 2011 and November 2013. Participants were children aged between 2–59 months presenting with fever measured by axillary temperature ≥37.5 °C at inclusion. Genotyping of haemoglobin S was done by PCR and malaria was diagnosed by Rapid Diagnostic Test. Research for viral and atypical bacterial respiratory pathogens was performed on nasopharyngeal swabs. Uni-and multivariate polytomous logistic regression was done to assess associations between microbiological results and SCD status, with HbAA phenotype as reference. RESULTS: A total of 807 children were analysed. Prevalence of SCD among febrile children was 2.4% (95% CI, 1.5–3.7%) and that of SCT was 23.8% (95% CI, 20.9–26.9%). There was no difference in the prevalence of malaria infection according to haemoglobin status (p = 0.3). Rhinovirus (22.5%), adenovirus (14.1%), and bocavirus (11.6%) were the most common respiratory pathogens detected. After univariate analysis, patients with SCD were more frequently infected by parechovirus (p = 0.01), while patients with SCT were more prone to RSV A or B infection (p = 0.01). After multivariate analysis, HbAS phenotype was associated with higher risk of RSV A and B infection compared to HbAA (adjusted OR = 1.9; 95% CI: 1.2–3.1, p = 0.009), while HbSS phenotype was associated with higher risk of parechovirus infection (adjusted OR = 6.0; 95% CI: 1.1–31.3, p = 0.03) compared to HbAA, independently of age, gender, period per quarter, and the other viruses. CONCLUSION: The prevalence of SCD among under-five children presenting with fever was high in the study population. No association was found between SCT and malaria but few viruses, especially parechovirus, seem to play an important role in the occurrence of pneumoniae among SCD patients.",2016 Dec 1,"['Maeder, Muriel N.', 'Rabezanahary, Henintsoa M.', 'Zafindraibe, Norosoa J.', 'Randriatiana, Martin Raoelina', 'Rasamoelina, Tahinamandranto', 'Rakotoarivo, Andry T.', 'Vanhems, Philippe', 'Hoffmann, Jonathan', 'Bénet, Thomas', 'Rakoto Andrianarivelo, Mala', 'Rakoto-Alson, Olivat A.']",BMC Hematol,,,True
41f31582cb50c99b10a376f465107d82bacf135c,PMC,The impact of epidemics on labor market: identifying victims of the Middle East Respiratory Syndrome in the Korean labor market,http://dx.doi.org/10.1186/s12939-016-0483-9,PMC5134239,27905938,CC BY,"BACKGROUND: The vulnerability approach suggests that disasters such as epidemics have different effects according not only to physical vulnerability but also to economic class (status). This paper examines the effect of the Middle East Respiratory Syndrome epidemic on the labor market to investigate whether vulnerable groups become more vulnerable due to an interaction between the socio-economic structure and physical risk. METHODS: This paper examines the effect of the Middle East Respiratory Syndrome epidemic on the labor market by considering unemployment status, job status, working hours, reason for unemployment and underemployment status. In particular, the study investigates whether the U-shaped curve becomes a J-shaped curve due to the interaction between medical vulnerability and labor market vulnerability after an outbreak, assuming that the relative vulnerability in the labor market by age shows a U curve with peaks for the young group and middle aged and old aged groups using the Economically Active Population Survey. We use the difference in difference approach and also conduct a falsification check and robustness check. RESULTS: The results suggest that older workers faced a higher possibility of unemployment after the Middle East Respiratory Syndrome outbreak. In particular, they experienced higher involuntary unemployment and underemployment status as well as decreased working hours. It was confirmed that the relative vulnerability of the labor market for older workers was higher than for the other age groups after the epidemic outbreak due to the double whammy of vulnerability in the medical and labor market. The vulnerability in the young group partially increased compared to the 30s and 40s age groups due to their relative vulnerability in the labor market despite being healthy. We find that assuming the relative vulnerability in the existing labor market shows a U shape with age increase, the U-shaped curve became J-shaped after the outbreak. CONCLUSIONS: Disasters like epidemics can occur unexpectedly and affect certain groups more than other. Therefore, medical protection should be enhanced for groups vulnerable to disease and economic measures are also required for the protection of their livelihoods in the labor market to prevent unemployment stemming from inequality.",2016 Dec 1,"['Lee, Ayoung', 'Cho, Joonmo']",Int J Equity Health,,,True
7f6d6d5cf7a484c164c955ff15a32758e1ab3943,PMC,An Investigation of the Outcomes of PGY Students’ Cognition of and Persistent Behavior in Learning through the Intervention of the Flipped Classroom in Taiwan,http://dx.doi.org/10.1371/journal.pone.0167598,PMC5135136,27911937,CC BY,"The Postgraduate Year (PGY) Program allows doctors-in-training to learn about the diagnosis, treatment and nursing of various common, general diseases. These items form the core curriculum and are mostly learned through caring for patients and clinical teaching. Doctors-in-training are evaluated for their knowledge through written tests or assignments, based on which the effectiveness of their training is also assessed; however, this generally produces a negative learning attitude among them. So we introduced the flipped classroom into PGY training program to change PGY students’ learning behavior. Although the flipped classroom is highly valued and has been practiced by teachers in schools of various levels, very few attempts have been made until now to report the learning outcomes achieved through the flipped classroom by means of rigorous research methods. Therefore we tried to employed Ajzen and Fishbein’s (1980) theory of reasoned action and Bandura’s self-efficacy to predict and explain the participants’ behavioral intention when participating in the core curriculum learning of the flipped classroom and to assess the change in students’ learning behavior and learning effectiveness. From August 2013 to July 2014, 39 PGY students from the General Surgery of the Tri-Service General Hospital were selected as the participants of this study. The control group included 43 students of the previous year, that is, the year before the intervention of the flipped classroom. A comparative analysis was performed. The questionnaire’s related matrices indicated highest correlation between self-efficacy and behavioral intention (r = 0.491, P < 0.01), followed by attitude (r = 0.365, P < 0.01) and subjective norms (r = 0.360, P < 0.01.) All three showed positive correlations with behavioral intention; among attitude, subjective norms, and self-efficacy, the pairwise correlations also reached significance level. The flipped classroom can indeed change PGY students’ the learning behavior from “passive learning” to “active learning.”",2016 Dec 2,"['Hsu, Sheng-Der', 'Chen, Cheng-Jueng', 'Chang, Wei-Kuo', 'Hu, Yih-Jin']",PLoS One,,,True
6cc00d24747f80a0e94f4dbdebcd9cc84b7e086f,PMC,An observational study of febrile seizures: the importance of viral infection and immunization,http://dx.doi.org/10.1186/s12887-016-0740-5,PMC5135752,27914475,CC BY,"BACKGROUND: Febrile seizures are common in young children. Annual peaks in incidence mirror increased respiratory virus activity during winter. Limited virological data are available using modern diagnostic techniques for children with febrile seizures. We aimed to determine the frequency of detection of specific viral pathogens in children with febrile seizures, to describe risk factors including recent vaccination and clinical features associated with specific etiologies. METHODS: An observational study was performed. Children aged 6 months to 5 years presenting to the Emergency Department of a tertiary children’s hospital in Western Australia with febrile seizures were enrolled between March 2012 and October 2013. Demographic, clinical data and vaccination history were collected, and virological testing was performed on per-nasal and per-rectal samples. RESULTS: One hundred fifty one patients (72 female; median age 1.7y; range 6 m-4y9m) were enrolled. Virological testing was completed for 143/151 (95%). At least one virus was detected in 102/143 patients (71%). The most commonly identified were rhinoviruses (31/143, 22%), adenovirus (30/151, 21%), enteroviruses, (28/143, 20%), influenza (19/143, 13%) and HHV6 (17/143, 12%). More than one virus was found in 48/143 (34%). No significant clinical differences were observed when children with a pathogen identified were compared with those with no pathogen detected. Febrile seizures occurred within 14 days of vaccine administration in 16/151 (11%). CONCLUSION: At least one virus was detected in over two thirds of cases tested (commonly picornaviruses, adenovirus and influenza). Viral co-infections were frequently identified. Febrile seizures occurred infrequently following immunization.",2016 Dec 3,"['Francis, Joshua R.', 'Richmond, Peter', 'Robins, Christine', 'Lindsay, Katie', 'Levy, Avram', 'Effler, Paul V.', 'Borland, Meredith', 'Blyth, Christopher C.']",BMC Pediatr,,,True
48c1c1a52958c6fd6f18ff10121c1336b9eb1395,PMC,China’s health assistance to Africa: opportunism or altruism?,http://dx.doi.org/10.1186/s12992-016-0217-1,PMC5135833,27912773,CC BY,"China has made substantial health commitments to Africa in the past several decades. However, while much has been written regarding China-Africa aid overall, relatively little attention has been given to China’s health aid. To better understand these investments, we provide an overview of the current framework and characteristics of China’s health aid to Africa. China’s health assistance has been perceived by some as opportunistic, largely as a demonstration of China’s engagement in “soft power” and an attempt to enhance its access to natural resources and political favors by African countries. Others have attributed altruistic intent, aiming to support the advancement of the health of populations in the African continent with a “no strings attached” approach. Our overview demonstrated that despite the magnitude of China’s health assistance, many questions remain regarding the scope of this aid, its effectiveness and the governance mechanisms that guide the conceptualization and implementation of such efforts. We also identified the need for a systematic and rigorous evaluation of the various elements of China’s health assistance to African countries in order to gain a deeper understanding of how priorities and allocations for health aid are determined, how such aid fits within the specific African country’s health strategies and to assess the effectiveness of such aid. Insights garnered through such an assessment could help determine future priorities for investment as well as inform efforts to optimize the value of China's aid for the populations of the recipient countries.",2016 Dec 3,"['Lin, Shuang', 'Gao, Liangmin', 'Reyes, Melissa', 'Cheng, Feng', 'Kaufman, Joan', 'El-Sadr, Wafaa M.']",Global Health,,,True
e28eedb8b780c3b08fa6a3d7d4c617f9587adc9a,PMC,Viral vector-based influenza vaccines,http://dx.doi.org/10.1080/21645515.2016.1210729,PMC5137548,27455345,CC BY,"Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors.",2016 Jul 25,"['de Vries, Rory D.', 'Rimmelzwaan, Guus F.']",Hum Vaccin Immunother,,,True
ef3d6cabc804e5eb587b34249b539c1b5efa4cc4,PMC,Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study,http://dx.doi.org/10.1038/srep38532,PMC5138590,27922126,CC BY,"Mixed viral and bacterial infections are widely described in community-acquired pneumonia; however, the clinical implications of co-infection on the associated immunopathology remain poorly studied. In this study, microRNA, mRNA and cytokine/chemokine secretion profiling were investigated for human monocyte-derived macrophages infected in-vitro with Influenza virus A/H1N1 and/or Streptococcus pneumoniae. We observed that the in-vitro co-infection synergistically increased interferon-γ-induced protein-10 (CXCL10, IP-10) expression compared to the singly-infected cells conditions. We demonstrated that endogenous miRNA-200a-3p, whose expression was synergistically induced following co-infection, indirectly regulates CXCL10 expression by targeting suppressor of cytokine signaling-6 (SOCS-6), a well-known regulator of the JAK-STAT signaling pathway. Additionally, in a subsequent clinical pilot study, immunomodulators levels were evaluated in samples from 74 children (≤5 years-old) hospitalized with viral and/or bacterial community-acquired pneumonia. Clinically, among the 74 cases of pneumonia, patients with identified mixed-detection had significantly higher (3.6-fold) serum IP-10 levels than those with a single detection (P = 0.03), and were significantly associated with severe pneumonia (P < 0.01). This study demonstrates that viral and bacterial co-infection modulates the JAK-STAT signaling pathway and leads to exacerbated IP-10 expression, which could play a major role in the pathogenesis of pneumonia.",2016 Dec 6,"['Hoffmann, Jonathan', 'Machado, Daniela', 'Terrier, Olivier', 'Pouzol, Stephane', 'Messaoudi, Mélina', 'Basualdo, Wilma', 'Espínola, Emilio E', 'Guillen, Rosa M.', 'Rosa-Calatrava, Manuel', 'Picot, Valentina', 'Bénet, Thomas', 'Endtz, Hubert', 'Russomando, Graciela', 'Paranhos-Baccalà, Gláucia']",Sci Rep,,,True
f18711ed6bde09aa40add3f7995993450056ec1d,PMC,Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study,http://dx.doi.org/10.1038/srep38532,PMC5138590,27922126,CC BY,"Mixed viral and bacterial infections are widely described in community-acquired pneumonia; however, the clinical implications of co-infection on the associated immunopathology remain poorly studied. In this study, microRNA, mRNA and cytokine/chemokine secretion profiling were investigated for human monocyte-derived macrophages infected in-vitro with Influenza virus A/H1N1 and/or Streptococcus pneumoniae. We observed that the in-vitro co-infection synergistically increased interferon-γ-induced protein-10 (CXCL10, IP-10) expression compared to the singly-infected cells conditions. We demonstrated that endogenous miRNA-200a-3p, whose expression was synergistically induced following co-infection, indirectly regulates CXCL10 expression by targeting suppressor of cytokine signaling-6 (SOCS-6), a well-known regulator of the JAK-STAT signaling pathway. Additionally, in a subsequent clinical pilot study, immunomodulators levels were evaluated in samples from 74 children (≤5 years-old) hospitalized with viral and/or bacterial community-acquired pneumonia. Clinically, among the 74 cases of pneumonia, patients with identified mixed-detection had significantly higher (3.6-fold) serum IP-10 levels than those with a single detection (P = 0.03), and were significantly associated with severe pneumonia (P < 0.01). This study demonstrates that viral and bacterial co-infection modulates the JAK-STAT signaling pathway and leads to exacerbated IP-10 expression, which could play a major role in the pathogenesis of pneumonia.",2016 Dec 6,"['Hoffmann, Jonathan', 'Machado, Daniela', 'Terrier, Olivier', 'Pouzol, Stephane', 'Messaoudi, Mélina', 'Basualdo, Wilma', 'Espínola, Emilio E', 'Guillen, Rosa M.', 'Rosa-Calatrava, Manuel', 'Picot, Valentina', 'Bénet, Thomas', 'Endtz, Hubert', 'Russomando, Graciela', 'Paranhos-Baccalà, Gláucia']",Sci Rep,,,False
6ebbce608cb316b579ed926190d068a6fa90534a,PMC,‘The Microbiome and the Pathophysiology of Asthma’,http://dx.doi.org/10.1186/s12931-016-0479-4,PMC5139145,27919249,CC BY,"Asthma is a chronic respiratory disease whose prevalence is increasing in the western world. Recently research has begun to focus on the role the microbiome plays in asthma pathogenesis in the hope of further understanding this respiratory disorder. Considered sterile until recently, the lungs have revealed themselves to contain a unique microbiota. A shift towards molecular methods for the quantification and sequencing of microbial DNA has revealed that the airways harbour a unique microbiota with apparent, reproducible differences present between healthy and diseased lungs. There is a hope that in classifying the microbial load of the asthmatic airway an insight may be afforded as to the possible role pulmonary microbes may have in propagating an asthmatic airway response. This could potentially pave the way for new therapeutic strategies for the treatment of chronic lung conditions such as asthma.",2016 Dec 5,"['Sullivan, Ashley', 'Hunt, Eoin', 'MacSharry, John', 'Murphy, Desmond M.']",Respir Res,,,True
d3cbb775040a7d1eac36c6615653b2d94f6c6c13,PMC,Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections,http://dx.doi.org/10.1038/emi.2016.69,PMC5141262,27436362,CC BY,"Surveillance for avian influenza viruses (AIVs) in poultry and environmental samples was conducted in four live-bird markets in Cambodia from January through November 2013. Through real-time RT-PCR testing, AIVs were detected in 45% of 1048 samples collected throughout the year. Detection rates ranged from 32% and 18% in duck and chicken swabs, respectively, to 75% in carcass wash water samples. Influenza A/H5N1 virus was detected in 79% of samples positive for influenza A virus and 35% of all samples collected. Sequence analysis of full-length haemagglutinin (HA) and neuraminidase (NA) genes from A/H5N1 viruses, and full-genome analysis of six representative isolates, revealed that the clade 1.1.2 reassortant virus associated with Cambodian human cases during 2013 was the only A/H5N1 virus detected during the year. However, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HA and NA genes revealed co-circulation of at least nine low pathogenic AIVs from HA1, HA2, HA3, HA4, HA6, HA7, HA9, HA10 and HA11 subtypes. Four repeated serological surveys were conducted throughout the year in a cohort of 125 poultry workers. Serological testing found an overall prevalence of 4.5% and 1.8% for antibodies to A/H5N1 and A/H9N2, respectively. Seroconversion rates of 3.7 and 0.9 cases per 1000 person-months participation were detected for A/H5N1 and A/H9N2, respectively. Peak AIV circulation was associated with the Lunar New Year festival. Knowledge of periods of increased circulation of avian influenza in markets should inform intervention measures such as market cleaning and closures to reduce risk of human infections and emergence of novel AIVs.",2016 Jul 20,"['Horm, Srey Viseth', 'Tarantola, Arnaud', 'Rith, Sareth', 'Ly, Sowath', 'Gambaretti, Juliette', 'Duong, Veasna', 'Y, Phalla', 'Sorn, San', 'Holl, Davun', 'Allal, Lotfi', 'Kalpravidh, Wantanee', 'Dussart, Philippe', 'Horwood, Paul F', 'Buchy, Philippe']",Emerg Microbes Infect,,,True
4ebf0b2d466494a1445783fc4c415a0ef8ecbd36,PMC,Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections,http://dx.doi.org/10.1038/emi.2016.69,PMC5141262,27436362,CC BY,"Surveillance for avian influenza viruses (AIVs) in poultry and environmental samples was conducted in four live-bird markets in Cambodia from January through November 2013. Through real-time RT-PCR testing, AIVs were detected in 45% of 1048 samples collected throughout the year. Detection rates ranged from 32% and 18% in duck and chicken swabs, respectively, to 75% in carcass wash water samples. Influenza A/H5N1 virus was detected in 79% of samples positive for influenza A virus and 35% of all samples collected. Sequence analysis of full-length haemagglutinin (HA) and neuraminidase (NA) genes from A/H5N1 viruses, and full-genome analysis of six representative isolates, revealed that the clade 1.1.2 reassortant virus associated with Cambodian human cases during 2013 was the only A/H5N1 virus detected during the year. However, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HA and NA genes revealed co-circulation of at least nine low pathogenic AIVs from HA1, HA2, HA3, HA4, HA6, HA7, HA9, HA10 and HA11 subtypes. Four repeated serological surveys were conducted throughout the year in a cohort of 125 poultry workers. Serological testing found an overall prevalence of 4.5% and 1.8% for antibodies to A/H5N1 and A/H9N2, respectively. Seroconversion rates of 3.7 and 0.9 cases per 1000 person-months participation were detected for A/H5N1 and A/H9N2, respectively. Peak AIV circulation was associated with the Lunar New Year festival. Knowledge of periods of increased circulation of avian influenza in markets should inform intervention measures such as market cleaning and closures to reduce risk of human infections and emergence of novel AIVs.",2016 Jul 20,"['Horm, Srey Viseth', 'Tarantola, Arnaud', 'Rith, Sareth', 'Ly, Sowath', 'Gambaretti, Juliette', 'Duong, Veasna', 'Y, Phalla', 'Sorn, San', 'Holl, Davun', 'Allal, Lotfi', 'Kalpravidh, Wantanee', 'Dussart, Philippe', 'Horwood, Paul F', 'Buchy, Philippe']",Emerg Microbes Infect,,,False
46934907d830de62eb5b4331a75b3332a9c0088c,PMC,Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections,http://dx.doi.org/10.1038/emi.2016.69,PMC5141262,27436362,CC BY,"Surveillance for avian influenza viruses (AIVs) in poultry and environmental samples was conducted in four live-bird markets in Cambodia from January through November 2013. Through real-time RT-PCR testing, AIVs were detected in 45% of 1048 samples collected throughout the year. Detection rates ranged from 32% and 18% in duck and chicken swabs, respectively, to 75% in carcass wash water samples. Influenza A/H5N1 virus was detected in 79% of samples positive for influenza A virus and 35% of all samples collected. Sequence analysis of full-length haemagglutinin (HA) and neuraminidase (NA) genes from A/H5N1 viruses, and full-genome analysis of six representative isolates, revealed that the clade 1.1.2 reassortant virus associated with Cambodian human cases during 2013 was the only A/H5N1 virus detected during the year. However, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HA and NA genes revealed co-circulation of at least nine low pathogenic AIVs from HA1, HA2, HA3, HA4, HA6, HA7, HA9, HA10 and HA11 subtypes. Four repeated serological surveys were conducted throughout the year in a cohort of 125 poultry workers. Serological testing found an overall prevalence of 4.5% and 1.8% for antibodies to A/H5N1 and A/H9N2, respectively. Seroconversion rates of 3.7 and 0.9 cases per 1000 person-months participation were detected for A/H5N1 and A/H9N2, respectively. Peak AIV circulation was associated with the Lunar New Year festival. Knowledge of periods of increased circulation of avian influenza in markets should inform intervention measures such as market cleaning and closures to reduce risk of human infections and emergence of novel AIVs.",2016 Jul 20,"['Horm, Srey Viseth', 'Tarantola, Arnaud', 'Rith, Sareth', 'Ly, Sowath', 'Gambaretti, Juliette', 'Duong, Veasna', 'Y, Phalla', 'Sorn, San', 'Holl, Davun', 'Allal, Lotfi', 'Kalpravidh, Wantanee', 'Dussart, Philippe', 'Horwood, Paul F', 'Buchy, Philippe']",Emerg Microbes Infect,,,False
49fd6f93367918d60b747f28a90e2ae4a85ff52a,PMC,Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections,http://dx.doi.org/10.1038/emi.2016.69,PMC5141262,27436362,CC BY,"Surveillance for avian influenza viruses (AIVs) in poultry and environmental samples was conducted in four live-bird markets in Cambodia from January through November 2013. Through real-time RT-PCR testing, AIVs were detected in 45% of 1048 samples collected throughout the year. Detection rates ranged from 32% and 18% in duck and chicken swabs, respectively, to 75% in carcass wash water samples. Influenza A/H5N1 virus was detected in 79% of samples positive for influenza A virus and 35% of all samples collected. Sequence analysis of full-length haemagglutinin (HA) and neuraminidase (NA) genes from A/H5N1 viruses, and full-genome analysis of six representative isolates, revealed that the clade 1.1.2 reassortant virus associated with Cambodian human cases during 2013 was the only A/H5N1 virus detected during the year. However, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HA and NA genes revealed co-circulation of at least nine low pathogenic AIVs from HA1, HA2, HA3, HA4, HA6, HA7, HA9, HA10 and HA11 subtypes. Four repeated serological surveys were conducted throughout the year in a cohort of 125 poultry workers. Serological testing found an overall prevalence of 4.5% and 1.8% for antibodies to A/H5N1 and A/H9N2, respectively. Seroconversion rates of 3.7 and 0.9 cases per 1000 person-months participation were detected for A/H5N1 and A/H9N2, respectively. Peak AIV circulation was associated with the Lunar New Year festival. Knowledge of periods of increased circulation of avian influenza in markets should inform intervention measures such as market cleaning and closures to reduce risk of human infections and emergence of novel AIVs.",2016 Jul 20,"['Horm, Srey Viseth', 'Tarantola, Arnaud', 'Rith, Sareth', 'Ly, Sowath', 'Gambaretti, Juliette', 'Duong, Veasna', 'Y, Phalla', 'Sorn, San', 'Holl, Davun', 'Allal, Lotfi', 'Kalpravidh, Wantanee', 'Dussart, Philippe', 'Horwood, Paul F', 'Buchy, Philippe']",Emerg Microbes Infect,,,False
e2c481329825d40d30efd7656bfbd28a3105707b,PMC,Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections,http://dx.doi.org/10.1038/emi.2016.69,PMC5141262,27436362,CC BY,"Surveillance for avian influenza viruses (AIVs) in poultry and environmental samples was conducted in four live-bird markets in Cambodia from January through November 2013. Through real-time RT-PCR testing, AIVs were detected in 45% of 1048 samples collected throughout the year. Detection rates ranged from 32% and 18% in duck and chicken swabs, respectively, to 75% in carcass wash water samples. Influenza A/H5N1 virus was detected in 79% of samples positive for influenza A virus and 35% of all samples collected. Sequence analysis of full-length haemagglutinin (HA) and neuraminidase (NA) genes from A/H5N1 viruses, and full-genome analysis of six representative isolates, revealed that the clade 1.1.2 reassortant virus associated with Cambodian human cases during 2013 was the only A/H5N1 virus detected during the year. However, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HA and NA genes revealed co-circulation of at least nine low pathogenic AIVs from HA1, HA2, HA3, HA4, HA6, HA7, HA9, HA10 and HA11 subtypes. Four repeated serological surveys were conducted throughout the year in a cohort of 125 poultry workers. Serological testing found an overall prevalence of 4.5% and 1.8% for antibodies to A/H5N1 and A/H9N2, respectively. Seroconversion rates of 3.7 and 0.9 cases per 1000 person-months participation were detected for A/H5N1 and A/H9N2, respectively. Peak AIV circulation was associated with the Lunar New Year festival. Knowledge of periods of increased circulation of avian influenza in markets should inform intervention measures such as market cleaning and closures to reduce risk of human infections and emergence of novel AIVs.",2016 Jul 20,"['Horm, Srey Viseth', 'Tarantola, Arnaud', 'Rith, Sareth', 'Ly, Sowath', 'Gambaretti, Juliette', 'Duong, Veasna', 'Y, Phalla', 'Sorn, San', 'Holl, Davun', 'Allal, Lotfi', 'Kalpravidh, Wantanee', 'Dussart, Philippe', 'Horwood, Paul F', 'Buchy, Philippe']",Emerg Microbes Infect,,,False
9cfada440e426dd4dabdb499d47ab2e7f9bad08c,PMC,Antiviral Innate Immune Response Interferes with the Formation of Replication-Associated Membrane Structures Induced by a Positive-Strand RNA Virus,http://dx.doi.org/10.1128/mBio.01991-16,PMC5142621,27923923,CC BY,"Infection with nidoviruses like corona- and arteriviruses induces a reticulovesicular network of interconnected endoplasmic reticulum (ER)-derived double-membrane vesicles (DMVs) and other membrane structures. This network is thought to accommodate the viral replication machinery and protect it from innate immune detection. We hypothesized that the innate immune response has tools to counteract the formation of these virus-induced replication organelles in order to inhibit virus replication. Here we have investigated the effect of type I interferon (IFN) treatment on the formation of arterivirus-induced membrane structures. Our approach involved ectopic expression of arterivirus nonstructural proteins nsp2 and nsp3, which induce DMV formation in the absence of other viral triggers of the interferon response, such as replicating viral RNA. Thus, this setup can be used to identify immune effectors that specifically target the (formation of) virus-induced membrane structures. Using large-scale electron microscopy mosaic maps, we found that IFN-β treatment significantly reduced the formation of the membrane structures. Strikingly, we also observed abundant stretches of double-membrane sheets (a proposed intermediate of DMV formation) in IFN-β-treated samples, suggesting the disruption of DMV biogenesis. Three interferon-stimulated gene products, two of which have been reported to target the hepatitis C virus replication structures, were tested for their possible involvement, but none of them affected membrane structure formation. Our study reveals the existence of a previously unknown innate immune mechanism that antagonizes the viral hijacking of host membranes. It also provides a solid basis for further research into the poorly understood interactions between the innate immune system and virus-induced replication structures.",2016 Dec 6,"['Oudshoorn, Diede', 'van der Hoeven, Barbara', 'Limpens, Ronald W. A. L.', 'Beugeling, Corrine', 'Snijder, Eric J.', 'Bárcena, Montserrat', 'Kikkert, Marjolein']",mBio,,,True
62af9e71368a90bd8fce0347e90527e3e4da3800,PMC,Type 1 Interferons and NK Cells Limit Murine Cytomegalovirus Escape from the Lymph Node Subcapsular Sinus,http://dx.doi.org/10.1371/journal.ppat.1006069,PMC5142805,27926941,CC0,"Cytomegaloviruses (CMVs) establish chronic, systemic infections. Peripheral infection spreads via lymph nodes, which are also a focus of host defence. Thus, this is a point at which systemic infection spread might be restricted. Subcapsular sinus macrophages (SSM) captured murine CMV (MCMV) from the afferent lymph and poorly supported its replication. Blocking the type I interferon (IFN-I) receptor (IFNAR) increased MCMV infection of SSM and of the fibroblastic reticular cells (FRC) lining the subcapsular sinus, and accelerated viral spread to the spleen. Little splenic virus derived from SSM, arguing that they mainly induce an anti-viral state in the otherwise susceptible FRC. NK cells also limited infection, killing infected FRC and causing tissue damage. They acted independently of IFN-I, as IFNAR blockade increased NK cell recruitment, and NK cell depletion increased infection in IFNAR-blocked mice. Thus SSM restricted MCMV infection primarily though IFN-I, with NK cells providing a second line of defence. The capacity of innate immunity to restrict MCMV escape from the subcapsular sinus suggested that enhancing its recruitment might improve infection control.",2016 Dec 7,"['Farrell, Helen E.', 'Bruce, Kimberley', 'Lawler, Clara', 'Cardin, Rhonda D.', 'Davis-Poynter, Nicholas J.', 'Stevenson, Philip G.']",PLoS Pathog,,,True
790261c395cc8a2413ec034f450e67e36f5e8b0f,PMC,Camels and Climate Resilience: Adaptation in Northern Kenya,http://dx.doi.org/10.1007/s10745-016-9858-1,PMC5143358,28018023,CC BY,"In the drylands of Africa, pastoralists have been facing new challenges, including those related to environmental shocks and stresses. In northern Kenya, under conditions of reduced rainfall and more frequent droughts, one response has been for pastoralists to focus increasingly on camel herding. Camels have started to be kept at higher altitudes and by people who rarely kept camels before. The development has been understood as a climate change adaptation strategy and as a means to improve climate resilience. Since 2003, development organizations have started to further the trend by distributing camels in the region. Up to now, little has been known about the nature of, reasons for, or ramifications of the increased reliance on camels. The paper addresses these questions and concludes that camels improve resilience in this dryland region, but only under certain climate change scenarios, and only for some groups.",2016 Nov 12,"['Watson, Elizabeth E.', 'Kochore, Hassan H.', 'Dabasso, Bulle Hallo']",Hum Ecol Interdiscip J,,,True
df61f934c991b4b4b08e1ec28804812ec0629ea1,PMC,TMEM2 inhibits hepatitis B virus infection in HepG2 and HepG2.2.15 cells by activating the JAK–STAT signaling pathway,http://dx.doi.org/10.1038/cddis.2016.146,PMC5143376,27253403,CC BY,"We have previously observed the downregulation of TMEM2 in the liver tissue of patients with chronic hepatitis B virus (HBV) infection and in HepG2.2.15 cells with HBV genomic DNA. In the present study, we investigated the role and mechanism of TMEM2 in HepG2 and HepG2.2.15 during HBV infection HepG2 and HepG2.2.15. HepG2 shTMEM2 cells with stable TMEM2 knockdown and HepG2 TMEM2 and HepG2.2.15 TMEM2 cells with stable TMEM2 overexpression were established using lentivirus vectors. We observed reduced expression of TMEM2 in HBV-infected liver tissues and HepG2.2.15 cells. HBsAg, HBcAg, HBV DNA, and HBV cccDNA levels were significantly increased in HepG2 shTMEM2 cells but decreased in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells compared with naive HepG2 cells. On the basis of the western blotting results, the JAK–STAT signaling pathway was inhibited in HepG2 shTMEM2 cells but activated in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells. In addition, reduced and increased expression of the antiviral proteins MxA and OAS1 was observed in TMEM2-silenced cells (HepG2 shTMEM2 cells) and TMEM2-overexpressing cells (HepG2 TMEM2 and HepG2.2.15 TMEM2 cells), respectively. The expression of Interferon regulatory factor 9 (IRF9) was not affected by TMEM2. However, we found that overexpression and knockdown of TMEM2, respectively, promoted and inhibited importation of IRF9 into nuclei. The luciferase reporter assay showed that IRF9 nuclear translocation affected interferon-stimulated response element activities. In addition, the inhibitory effects of TMEM2 on HBV infection in HepG2 shTMEM2 cells was significantly enhanced by pre-treatment with interferon but significantly inhibited in HepG2.2.15 TMEM2 cells by pre-treatment with JAK1 inhibitor. TMEM2 inhibits HBV infection in HepG2 and HepG2.2.15 by activating the JAK–STAT signaling pathway.",2016 Jun 2,"['Zhu, X', 'Xie, C', 'Li, Y-m', 'Huang, Z-l', 'Zhao, Q-y', 'Hu, Z-x', 'Wang, P-p', 'Gu, Y-r', 'Gao, Z-l', 'Peng, L']",Cell Death Dis,,,True
3a5bfccbd47694771018f0ee03b0eeedfeeb2ef9,PMC,Spatiotemporal Analysis of the 2014 Ebola Epidemic in West Africa,http://dx.doi.org/10.1371/journal.pcbi.1005210,PMC5145133,27930675,CC BY,"In 2014–2016, Guinea, Sierra Leone and Liberia in West Africa experienced the largest and longest Ebola epidemic since the discovery of the virus in 1976. During the epidemic, incidence data were collected and published at increasing resolution. To monitor the epidemic as it spread within and between districts, we develop an analysis method that exploits the full spatiotemporal resolution of the data by combining a local model for time-varying effective reproduction numbers with a gravity-type model for spatial dispersion of the infection. We test this method in simulations and apply it to the weekly incidences of confirmed and probable cases per district up to June 2015, as reported by the World Health Organization. Our results indicate that, of the newly infected cases, only a small percentage, between 4% and 10%, migrates to another district, and a minority of these migrants, between 0% and 23%, leave their country. The epidemics in the three countries are found to be similar in estimated effective reproduction numbers, and in the probability of importing infection into a district. The countries might have played different roles in cross-border transmissions, although a sensitivity analysis suggests that this could also be related to underreporting. The spatiotemporal analysis method can exploit available longitudinal incidence data at different geographical locations to monitor local epidemics, determine the extent of spatial spread, reveal the contribution of local and imported cases, and identify sources of introductions in uninfected areas. With good quality data on incidence, this data-driven method can help to effectively control emerging infections.",2016 Dec 8,"['Backer, Jantien A.', 'Wallinga, Jacco']",PLoS Comput Biol,,,True
126fe65d101309b6cfa1b133e0036082572b49d8,PMC,Spatiotemporal Analysis of the 2014 Ebola Epidemic in West Africa,http://dx.doi.org/10.1371/journal.pcbi.1005210,PMC5145133,27930675,CC BY,"In 2014–2016, Guinea, Sierra Leone and Liberia in West Africa experienced the largest and longest Ebola epidemic since the discovery of the virus in 1976. During the epidemic, incidence data were collected and published at increasing resolution. To monitor the epidemic as it spread within and between districts, we develop an analysis method that exploits the full spatiotemporal resolution of the data by combining a local model for time-varying effective reproduction numbers with a gravity-type model for spatial dispersion of the infection. We test this method in simulations and apply it to the weekly incidences of confirmed and probable cases per district up to June 2015, as reported by the World Health Organization. Our results indicate that, of the newly infected cases, only a small percentage, between 4% and 10%, migrates to another district, and a minority of these migrants, between 0% and 23%, leave their country. The epidemics in the three countries are found to be similar in estimated effective reproduction numbers, and in the probability of importing infection into a district. The countries might have played different roles in cross-border transmissions, although a sensitivity analysis suggests that this could also be related to underreporting. The spatiotemporal analysis method can exploit available longitudinal incidence data at different geographical locations to monitor local epidemics, determine the extent of spatial spread, reveal the contribution of local and imported cases, and identify sources of introductions in uninfected areas. With good quality data on incidence, this data-driven method can help to effectively control emerging infections.",2016 Dec 8,"['Backer, Jantien A.', 'Wallinga, Jacco']",PLoS Comput Biol,,,False
d955f71fe354a87e671999a6a0a17b88376bcf8c,PMC,Allelic Variation in CXCL16 Determines CD3(+) T Lymphocyte Susceptibility to Equine Arteritis Virus Infection and Establishment of Long-Term Carrier State in the Stallion,http://dx.doi.org/10.1371/journal.pgen.1006467,PMC5145142,27930647,CC BY,"Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of horses and other equid species. Following natural infection, 10–70% of the infected stallions can become persistently infected and continue to shed EAV in their semen for periods ranging from several months to life. Recently, we reported that some stallions possess a subpopulation(s) of CD3(+) T lymphocytes that are susceptible to in vitro EAV infection and that this phenotypic trait is associated with long-term carrier status following exposure to the virus. In contrast, stallions not possessing the CD3(+) T lymphocyte susceptible phenotype are at less risk of becoming long-term virus carriers. A genome wide association study (GWAS) using the Illumina Equine SNP50 chip revealed that the ability of EAV to infect CD3(+) T lymphocytes and establish long-term carrier status in stallions correlated with a region within equine chromosome 11. Here we identified the gene and mutations responsible for these phenotypes. Specifically, the work implicated three allelic variants of the equine orthologue of CXCL16 (EqCXCL16) that differ by four non-synonymous nucleotide substitutions (XM_00154756; c.715 A → T, c.801 G → C, c.804 T → A/G, c.810 G → A) within exon 1. This resulted in four amino acid changes with EqCXCL16S (XP_001504806.1) having Phe, His, Ile and Lys as compared to EqCXL16R having Tyr, Asp, Phe, and Glu at 40, 49, 50, and 52, respectively. Two alleles (EqCXCL16Sa, EqCXCL16Sb) encoded identical protein products that correlated strongly with long-term EAV persistence in stallions (P<0.000001) and are required for in vitro CD3(+) T lymphocyte susceptibility to EAV infection. The third (EqCXCL16R) was associated with in vitro CD3(+) T lymphocyte resistance to EAV infection and a significantly lower probability for establishment of the long-term carrier state (viral persistence) in the male reproductive tract. EqCXCL16Sa and EqCXCL16Sb exert a dominant mode of inheritance. Most importantly, the protein isoform EqCXCL16S but not EqCXCL16R can function as an EAV cellular receptor. Although both molecules have equal chemoattractant potential, EqCXCL16S has significantly higher scavenger receptor and adhesion properties compared to EqCXCL16R.",2016 Dec 8,"['Sarkar, Sanjay', 'Bailey, Ernest', 'Go, Yun Young', 'Cook, R. Frank', 'Kalbfleisch, Ted', 'Eberth, John', 'Chelvarajan, R. Lakshman', 'Shuck, Kathleen M.', 'Artiushin, Sergey', 'Timoney, Peter J.', 'Balasuriya, Udeni B. R.']",PLoS Genet,,,True
dcf9e10df84c4439f2fb380b472de9ef2a6e55b8,PMC,Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids,http://dx.doi.org/10.1371/journal.pone.0167651,PMC5145171,27930687,CC BY,"Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.",2016 Dec 8,"['Das, Jayanta Kumar', 'Das, Provas', 'Ray, Korak Kumar', 'Choudhury, Pabitra Pal', 'Jana, Siddhartha Sankar']",PLoS One,,,True
4d61140dd3e58146f186edd06dba73088ec9cafa,PMC,Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids,http://dx.doi.org/10.1371/journal.pone.0167651,PMC5145171,27930687,CC BY,"Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.",2016 Dec 8,"['Das, Jayanta Kumar', 'Das, Provas', 'Ray, Korak Kumar', 'Choudhury, Pabitra Pal', 'Jana, Siddhartha Sankar']",PLoS One,,,False
4bb766c79e1d3c5605e0007a1a077813f6a67a8c,PMC,Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids,http://dx.doi.org/10.1371/journal.pone.0167651,PMC5145171,27930687,CC BY,"Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.",2016 Dec 8,"['Das, Jayanta Kumar', 'Das, Provas', 'Ray, Korak Kumar', 'Choudhury, Pabitra Pal', 'Jana, Siddhartha Sankar']",PLoS One,,,False
8e8e7ae819676089e49cb3eed7ae90e7d21ca68e,PMC,Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids,http://dx.doi.org/10.1371/journal.pone.0167651,PMC5145171,27930687,CC BY,"Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.",2016 Dec 8,"['Das, Jayanta Kumar', 'Das, Provas', 'Ray, Korak Kumar', 'Choudhury, Pabitra Pal', 'Jana, Siddhartha Sankar']",PLoS One,,,False
2f0b14bfd68f76cc8dd457afc675bbff500b8cd2,PMC,Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids,http://dx.doi.org/10.1371/journal.pone.0167651,PMC5145171,27930687,CC BY,"Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.",2016 Dec 8,"['Das, Jayanta Kumar', 'Das, Provas', 'Ray, Korak Kumar', 'Choudhury, Pabitra Pal', 'Jana, Siddhartha Sankar']",PLoS One,,,False
39d6d2420dada4c072e5f7122c40a3305f6c93f6,PMC,Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids,http://dx.doi.org/10.1371/journal.pone.0167651,PMC5145171,27930687,CC BY,"Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.",2016 Dec 8,"['Das, Jayanta Kumar', 'Das, Provas', 'Ray, Korak Kumar', 'Choudhury, Pabitra Pal', 'Jana, Siddhartha Sankar']",PLoS One,,,False
3deebe55bc1ee1b20e045ec3474c46faed3b38ee,PMC,Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids,http://dx.doi.org/10.1371/journal.pone.0167651,PMC5145171,27930687,CC BY,"Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.",2016 Dec 8,"['Das, Jayanta Kumar', 'Das, Provas', 'Ray, Korak Kumar', 'Choudhury, Pabitra Pal', 'Jana, Siddhartha Sankar']",PLoS One,,,False
b1e1e1ca56fc522da3ae2ffbfa4ade922af4e2fe,PMC,Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids,http://dx.doi.org/10.1371/journal.pone.0167651,PMC5145171,27930687,CC BY,"Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.",2016 Dec 8,"['Das, Jayanta Kumar', 'Das, Provas', 'Ray, Korak Kumar', 'Choudhury, Pabitra Pal', 'Jana, Siddhartha Sankar']",PLoS One,,,False
e319e1968d1de70b511e1b51fa5a69b3c75e41d4,PMC,Both Cerebral and Hematopoietic Deficiencies in CCR2 Result in Uncontrolled Herpes Simplex Virus Infection of the Central Nervous System in Mice,http://dx.doi.org/10.1371/journal.pone.0168034,PMC5145225,27930721,CC BY,"CCR2 is a chemokine receptor expressed on the surface of blood leukocytes, particularly «Ly6C(hi)» inflammatory monocytes and microglia. Signaling through this receptor is thought to influence the immune activity of microglia as well as monocytes egress from the bone marrow (BM) and their trafficking into the central nervous system (CNS) in several neurological diseases. During experimental herpes simplex virus 1 (HSV-1) encephalitis (HSE), CCR2 deficiency has been reported to exacerbate the outcome of the disease. However, the precise contribution of CCR2 expressed in cells of the CNS or peripheral monocytes in the protection against HSE remains unclear. To dissect the differential role of CCR2 during HSE, chimeric mice with receptor deficiency in the brain or blood cells were generated by transplanting wild-type (WT) C57BL/6 or CCR2(-/-) BM-derived cells in CCR2(-/-) (WT→CCR2(-/-)) and WT (CCR2(-/-)→WT) mice, respectively. Our results indicate that following intranasal infection with 1.2x10(6) plaque forming units of HSV-1, CCR2 deficiency in hematopoietic cells and, to a lesser extent, in CNS exacerbates the outcome of HSE. Mortality rates of CCR2(-/-) (71.4%) and CCR2(-/-)→WT (57.1%) mice were significantly higher than that of WT (15.3%; P<0.01 and P<0.05, respectively) but the difference did not reach statistical significance for WT→CCR2(-/-) animals (42.8%; P = 0.16). Both peripheral and CNS deficiencies in CCR2 resulted in increased infectious viral titers and wider dissemination of HSV antigens in the brain as well as an overproduction of inflammatory cytokines and chemokines including IL-1β, IL-6, CCL2, CCL3 and CCL5. Furthermore, CCR2 deficiency in the hematopoietic system altered monocytes egress from the BM and their recruitment to the CNS, which may contribute to the failure in HSV-1 containment. Collectively, these data suggest that CCR2 expressed on cells of CNS and especially on peripheral monocytes is important for the control of HSV-1 replication and inflammatory environment during experimental HSE.",2016 Dec 8,"['Menasria, Rafik', 'Canivet, Coraline', 'Piret, Jocelyne', 'Gosselin, Jean', 'Boivin, Guy']",PLoS One,,,True
9a60f844dc6dd4f0c5ddfc02fb970a04702eb388,PMC,Both Cerebral and Hematopoietic Deficiencies in CCR2 Result in Uncontrolled Herpes Simplex Virus Infection of the Central Nervous System in Mice,http://dx.doi.org/10.1371/journal.pone.0168034,PMC5145225,27930721,CC BY,"CCR2 is a chemokine receptor expressed on the surface of blood leukocytes, particularly «Ly6C(hi)» inflammatory monocytes and microglia. Signaling through this receptor is thought to influence the immune activity of microglia as well as monocytes egress from the bone marrow (BM) and their trafficking into the central nervous system (CNS) in several neurological diseases. During experimental herpes simplex virus 1 (HSV-1) encephalitis (HSE), CCR2 deficiency has been reported to exacerbate the outcome of the disease. However, the precise contribution of CCR2 expressed in cells of the CNS or peripheral monocytes in the protection against HSE remains unclear. To dissect the differential role of CCR2 during HSE, chimeric mice with receptor deficiency in the brain or blood cells were generated by transplanting wild-type (WT) C57BL/6 or CCR2(-/-) BM-derived cells in CCR2(-/-) (WT→CCR2(-/-)) and WT (CCR2(-/-)→WT) mice, respectively. Our results indicate that following intranasal infection with 1.2x10(6) plaque forming units of HSV-1, CCR2 deficiency in hematopoietic cells and, to a lesser extent, in CNS exacerbates the outcome of HSE. Mortality rates of CCR2(-/-) (71.4%) and CCR2(-/-)→WT (57.1%) mice were significantly higher than that of WT (15.3%; P<0.01 and P<0.05, respectively) but the difference did not reach statistical significance for WT→CCR2(-/-) animals (42.8%; P = 0.16). Both peripheral and CNS deficiencies in CCR2 resulted in increased infectious viral titers and wider dissemination of HSV antigens in the brain as well as an overproduction of inflammatory cytokines and chemokines including IL-1β, IL-6, CCL2, CCL3 and CCL5. Furthermore, CCR2 deficiency in the hematopoietic system altered monocytes egress from the BM and their recruitment to the CNS, which may contribute to the failure in HSV-1 containment. Collectively, these data suggest that CCR2 expressed on cells of CNS and especially on peripheral monocytes is important for the control of HSV-1 replication and inflammatory environment during experimental HSE.",2016 Dec 8,"['Menasria, Rafik', 'Canivet, Coraline', 'Piret, Jocelyne', 'Gosselin, Jean', 'Boivin, Guy']",PLoS One,,,False
efcd7d171bb51acf2ef0a631901900497957a3be,PMC,Relationship between hepcidin and oxidant/antioxidant status in calves with suspected neonatal septicemia,http://dx.doi.org/10.14202/vetworld.2016.1238-1241,PMC5146304,27956775,CC BY,"AIM: This study has been conducted for the purpose of determining serum hepcidin, total antioxidant status (TAS), total oxidant status (TOS), and Fe levels in calves with suspected neonatal septicemia before and after treatment and the clinical significance of hepcidin in calves with suspected neonatal septicemia. MATERIALS AND METHODS: The study material consisted of 15 calves of different ages and sexes brought to the Training, Research and Application Center at the Kafkas University Faculty of Veterinary Medicine with suspected neonatal septicemia. 8.5 mL of blood was drawn from the jugular vein of each animal into coagulant tubes before and after treatment for one-off biochemical analyses and centrifuged. After this, the serum was separated. Hepcidin, TAS, TOS, and Fe levels in the serum were measured. RESULTS: While pre-treatment hepcidin levels were 58.42±3.46 ng/mL, post-treatment levels were 46.87±2.98 ng/mL (p<0.05). Pre-treatment Fe levels were 60.13±7.27 µg/dl, while post-treatment levels were 83.1±8.09 µg/dl (p<0.05). The changes in the TAS and TOS levels were also found to be statistically significant. CONCLUSION: In light of the fact that hepcidin plays a role function in the regulation of Fe as well as the fact that Fe is a significant nutritional source for many microorganisms, it was concluded that hepcidin may play a significant role in nutritional immunity and the pathogenesis of diseases.",2016 Nov 14,"['Erkilic, E. E.', 'Erdogan, H. M.', 'Ogun, M.', 'Kirmizigul, A. H.', 'Gokce, E.', 'Kuru, M.', 'Kukurt, A.']",Vet World,,,True
b3fc1f4cd16b65fb6454b7c2705a95aee4419c46,PMC,Seroprevalence of Rotavirus infection in pig population of Arunachal Pradesh,http://dx.doi.org/10.14202/vetworld.2016.1300-1304,PMC5146314,27956785,CC BY,"AIM: This study was conducted to find out the seroprevalence of Rotavirus(RV) infection among the pig population of Arunachal Pradesh. MATERIALS AND METHODS: Serums samples were collected from piglets of age ranging from 1 week to 6 months and the sows associated with the piglets that were reared under organized and unorganized system of management in six different districts of Arunachal Pradesh. The prevalence of RV specific antibodies was detected using a polyclonal antibody-based indirect enzyme-linked immunosorbent assay (i-ELISA). RESULTS: The study revealed that out of 394 serum samples, 255 (64.72%) samples were found to be positive for RV-specific antibody in i-ELISA. Considering the samples from different districts, Papumpare district of Arunachal Pradesh showed highest numbers of seropositive animals (68.75%) followed by upper Subansiri (64.91%) while West Siang district showed lowest positivity rate (61.22%). CONCLUSION: As considerable seropositivity was recorded among pig population of Arunachal Pradesh in this study, there is urgent need to establish high-impact and cost-effective public health intervention tools, key among them being the introduction of strict hygiene practice and RV vaccination program, to greatly reduce the number of deaths due to diarrheal diseases. To the authors’ knowledge, this is the first report on the prevalence of RV infection from pigs of Arunachal Pradesh.",2016 Nov 27,"['Garam, G. B.', 'Bora, D. P.', 'Borah, B.', 'Bora, M.', 'Das, S. K.']",Vet World,,,True
c8c7265b3435763dfb209e8895c83e3cf8717a0f,PMC,Web-based infectious disease surveillance systems and public health perspectives: a systematic review,http://dx.doi.org/10.1186/s12889-016-3893-0,PMC5146908,27931204,CC BY,"BACKGROUND: Emerging and re-emerging infectious diseases are a significant public health concern, and early detection and immediate response is crucial for disease control. These challenges have led to the need for new approaches and technologies to reinforce the capacity of traditional surveillance systems for detecting emerging infectious diseases. In the last few years, the availability of novel web-based data sources has contributed substantially to infectious disease surveillance. This study explores the burgeoning field of web-based infectious disease surveillance systems by examining their current status, importance, and potential challenges. METHODS: A systematic review framework was applied to the search, screening, and analysis of web-based infectious disease surveillance systems. We searched PubMed, Web of Science, and Embase databases to extensively review the English literature published between 2000 and 2015. Eleven surveillance systems were chosen for evaluation according to their high frequency of application. Relevant terms, including newly coined terms, development and classification of the surveillance systems, and various characteristics associated with the systems were studied. RESULTS: Based on a detailed and informative review of the 11 web-based infectious disease surveillance systems, it was evident that these systems exhibited clear strengths, as compared to traditional surveillance systems, but with some limitations yet to be overcome. The major strengths of the newly emerging surveillance systems are that they are intuitive, adaptable, low-cost, and operated in real-time, all of which are necessary features of an effective public health tool. The most apparent potential challenges of the web-based systems are those of inaccurate interpretation and prediction of health status, and privacy issues, based on an individual’s internet activity. CONCLUSION: Despite being in a nascent stage with further modification needed, web-based surveillance systems have evolved to complement traditional national surveillance systems. This review highlights ways in which the strengths of existing systems can be maintained and weaknesses alleviated to implement optimal web surveillance systems. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-016-3893-0) contains supplementary material, which is available to authorized users.",2016 Dec 8,"['Choi, Jihye', 'Cho, Youngtae', 'Shim, Eunyoung', 'Woo, Hyekyung']",BMC Public Health,,,True
d7a83aa4ab9b3fb17d6fbb6d7fb5e71f3939135f,PMC,Unlocking bat immunology: establishment of Pteropus alecto bone marrow-derived dendritic cells and macrophages,http://dx.doi.org/10.1038/srep38597,PMC5146944,27934903,CC BY,"Bats carry and shed many emerging infectious disease agents including Ebola virus and SARS-like Coronaviruses, yet they rarely display clinical symptoms of infection. Bat epithelial or fibroblast cell lines were previously established to study the bat immune response against viral infection. However, the lack of professional immune cells such as dendritic cells (DC) and macrophages has greatly limited the significance of current investigations. Using Pteropus alecto (P. alecto) GM-CSF plus IL4, FLT3L and CSF-1, we successfully generated bat bone marrow-derived DC and macrophages. Cells with the phenotype, morphology and functional features of monocyte-derived DC, bona fide DC or macrophages were obtained in GM-CSF/IL4, FLT3L or CSF-1 cultures, respectively. The successful generation of the first bat bone marrow-derived immune cells paves the way to unlocking the immune mechanisms that confer host resilience to pathogens in bats.",2016 Dec 9,"['Zhou, Peng', 'Chionh, Yok Teng', 'Irac, Sergio Erdal', 'Ahn, Matae', 'Jia Ng, Justin Han', 'Fossum, Even', 'Bogen, Bjarne', 'Ginhoux, Florent', 'Irving, Aaron T', 'Dutertre, Charles-Antoine', 'Wang, Lin-Fa']",Sci Rep,,,True
4c437d37580c52301f130919d2d0f410efb2a1f9,PMC,Unlocking bat immunology: establishment of Pteropus alecto bone marrow-derived dendritic cells and macrophages,http://dx.doi.org/10.1038/srep38597,PMC5146944,27934903,CC BY,"Bats carry and shed many emerging infectious disease agents including Ebola virus and SARS-like Coronaviruses, yet they rarely display clinical symptoms of infection. Bat epithelial or fibroblast cell lines were previously established to study the bat immune response against viral infection. However, the lack of professional immune cells such as dendritic cells (DC) and macrophages has greatly limited the significance of current investigations. Using Pteropus alecto (P. alecto) GM-CSF plus IL4, FLT3L and CSF-1, we successfully generated bat bone marrow-derived DC and macrophages. Cells with the phenotype, morphology and functional features of monocyte-derived DC, bona fide DC or macrophages were obtained in GM-CSF/IL4, FLT3L or CSF-1 cultures, respectively. The successful generation of the first bat bone marrow-derived immune cells paves the way to unlocking the immune mechanisms that confer host resilience to pathogens in bats.",2016 Dec 9,"['Zhou, Peng', 'Chionh, Yok Teng', 'Irac, Sergio Erdal', 'Ahn, Matae', 'Jia Ng, Justin Han', 'Fossum, Even', 'Bogen, Bjarne', 'Ginhoux, Florent', 'Irving, Aaron T', 'Dutertre, Charles-Antoine', 'Wang, Lin-Fa']",Sci Rep,,,False
a3c3313dedf5e05ca7bc7388ff9471ff7032ef54,PMC,Ultrasensitive Detection of Porcine Epidemic Diarrhea Virus from Fecal Samples Using Functionalized Nanoparticles,http://dx.doi.org/10.1371/journal.pone.0167325,PMC5147876,27936019,CC BY,"Porcine epidemic diarrhea virus (PEDV) is the main causative agent of porcine diarrhea, which has resulted in devastating damage to swine industry and become a perplexed global problem. PEDV infection causes lesions and clinical symptoms, and infected pigs often succumb to severe dehydration. If there is not a timely and effective method to control its infection, PEDV will spread rapidly across the whole swine farm. Therefore, preclinical identification of PEDV is of great significance for preventing the outbreak and spread of this disease. In this study, a functionalized nanoparticles-based PCR method (UNDP-PCR) specific for PEDV was developed through systematic optimization of functionalized magnetic beads and gold nanoparticles which were further used to specifically enrich viral RNA from the lysate of PEDV stool samples, forming a MMPs-RNA-AuNPs complex. Then, oligonucleotides specific for PEDV coated on AuNPs were eluted from the complex and were further amplified and characterized by PCR. The detection limitation of the established UNDP-PCR method for PEDV was 25 copies in per gram PEDV stool samples, which is 400-fold more sensitive than conventional RT-PCR for stool samples. The UNDP-PCR for PEDV exhibited reliable reproducibility and high specificity, no cross-reaction was observed with other porcine viruses. In 153 preclinical fecal samples, the positive detection rate of UNDP-PCR specific for PEDV (30.72%) was much higher than that of conventional RT-PCR (5.88%) and SYBR Green real-time RT-PCR. In a word, this study provided a RNA extraction and transcription free, rapid and economical method for preclinical PEDV infection, which showed higher sensitivity, specificity and reproducibility, and exhibited application potency for evaluating viral loads of preclinical samples.",2016 Dec 9,"['Xing, Na', 'Guan, Xiaoxiao', 'An, Bin', 'Cui, Beibei', 'Wang, Zengguo', 'Wang, Xiaoya', 'Zhang, Xiujuan', 'Du, Qian', 'Zhao, Xiaomin', 'Huang, Yong', 'Tong, Dewen']",PLoS One,,,True
fc221d8af0a962a17778721217b1f9f914f353b4,PMC,Characterization of anti-MERS-CoV antibodies against various recombinant structural antigens of MERS-CoV in an imported case in China,http://dx.doi.org/10.1038/emi.2016.114,PMC5148018,27826140,CC BY,"The first imported case of Middle East respiratory syndrome (MERS) in China recently occurred, allowing for the characterization of antibody titers in a series of the patient's sera using the following methods based on recombinant viral structural antigens: inactivated MERS coronavirus (MERS-CoV) enzyme-linked immunosorbent assay (ELISA), recombinant MERS-CoV spike (S, or fragments of S) ELISA, nucleoprotein (NP) ELISA and MERS S pseudovirus particle-based neutralization test (ppNT). A longitudinal profile of the infection showed that seroconversion detected by ELISAs based on the recombinant extracellular domain, S, S1 and receptor-binding domain (RBD) antigens occurred as early as neutralizing antibodies were detected by the ppNT and earlier than antibodies were detected by the inactivated MERS-CoV and N-terminal domain (NTD) ELISAs. Antibodies detected by the NP ELISA occurred last. Strong correlations were found between the S1, RBD and NP ELISAs and the inactivated MERS-CoV ELISA. The S and RBD ELISAs were highly correlated with the commercial S1 ELISA. The S ELISA strongly correlated with the ppNT, although the MERS-CoV, S1, NTD and RBD ELISAs were also significantly correlated with the ppNT (P<0.001).",2016 Nov 9,"['Wang, Wenling', 'Wang, Huijuan', 'Deng, Yao', 'Song, Tie', 'Lan, Jiaming', 'Wu, Guizhen', 'Ke, Changwen', 'Tan, Wenjie']",Emerg Microbes Infect,,,True
b8cdd8c40d99073c91a2146a4ea2a2da5c04d808,PMC,Characterization of anti-MERS-CoV antibodies against various recombinant structural antigens of MERS-CoV in an imported case in China,http://dx.doi.org/10.1038/emi.2016.114,PMC5148018,27826140,CC BY,"The first imported case of Middle East respiratory syndrome (MERS) in China recently occurred, allowing for the characterization of antibody titers in a series of the patient's sera using the following methods based on recombinant viral structural antigens: inactivated MERS coronavirus (MERS-CoV) enzyme-linked immunosorbent assay (ELISA), recombinant MERS-CoV spike (S, or fragments of S) ELISA, nucleoprotein (NP) ELISA and MERS S pseudovirus particle-based neutralization test (ppNT). A longitudinal profile of the infection showed that seroconversion detected by ELISAs based on the recombinant extracellular domain, S, S1 and receptor-binding domain (RBD) antigens occurred as early as neutralizing antibodies were detected by the ppNT and earlier than antibodies were detected by the inactivated MERS-CoV and N-terminal domain (NTD) ELISAs. Antibodies detected by the NP ELISA occurred last. Strong correlations were found between the S1, RBD and NP ELISAs and the inactivated MERS-CoV ELISA. The S and RBD ELISAs were highly correlated with the commercial S1 ELISA. The S ELISA strongly correlated with the ppNT, although the MERS-CoV, S1, NTD and RBD ELISAs were also significantly correlated with the ppNT (P<0.001).",2016 Nov 9,"['Wang, Wenling', 'Wang, Huijuan', 'Deng, Yao', 'Song, Tie', 'Lan, Jiaming', 'Wu, Guizhen', 'Ke, Changwen', 'Tan, Wenjie']",Emerg Microbes Infect,,,False
fd63c849581a31e107d1f6af269c3cb152b565b5,PMC,Characterization of anti-MERS-CoV antibodies against various recombinant structural antigens of MERS-CoV in an imported case in China,http://dx.doi.org/10.1038/emi.2016.114,PMC5148018,27826140,CC BY,"The first imported case of Middle East respiratory syndrome (MERS) in China recently occurred, allowing for the characterization of antibody titers in a series of the patient's sera using the following methods based on recombinant viral structural antigens: inactivated MERS coronavirus (MERS-CoV) enzyme-linked immunosorbent assay (ELISA), recombinant MERS-CoV spike (S, or fragments of S) ELISA, nucleoprotein (NP) ELISA and MERS S pseudovirus particle-based neutralization test (ppNT). A longitudinal profile of the infection showed that seroconversion detected by ELISAs based on the recombinant extracellular domain, S, S1 and receptor-binding domain (RBD) antigens occurred as early as neutralizing antibodies were detected by the ppNT and earlier than antibodies were detected by the inactivated MERS-CoV and N-terminal domain (NTD) ELISAs. Antibodies detected by the NP ELISA occurred last. Strong correlations were found between the S1, RBD and NP ELISAs and the inactivated MERS-CoV ELISA. The S and RBD ELISAs were highly correlated with the commercial S1 ELISA. The S ELISA strongly correlated with the ppNT, although the MERS-CoV, S1, NTD and RBD ELISAs were also significantly correlated with the ppNT (P<0.001).",2016 Nov 9,"['Wang, Wenling', 'Wang, Huijuan', 'Deng, Yao', 'Song, Tie', 'Lan, Jiaming', 'Wu, Guizhen', 'Ke, Changwen', 'Tan, Wenjie']",Emerg Microbes Infect,,,False
979b57435d23b8a685e05afe29b41c6f7aa73336,PMC,Characterization of anti-MERS-CoV antibodies against various recombinant structural antigens of MERS-CoV in an imported case in China,http://dx.doi.org/10.1038/emi.2016.114,PMC5148018,27826140,CC BY,"The first imported case of Middle East respiratory syndrome (MERS) in China recently occurred, allowing for the characterization of antibody titers in a series of the patient's sera using the following methods based on recombinant viral structural antigens: inactivated MERS coronavirus (MERS-CoV) enzyme-linked immunosorbent assay (ELISA), recombinant MERS-CoV spike (S, or fragments of S) ELISA, nucleoprotein (NP) ELISA and MERS S pseudovirus particle-based neutralization test (ppNT). A longitudinal profile of the infection showed that seroconversion detected by ELISAs based on the recombinant extracellular domain, S, S1 and receptor-binding domain (RBD) antigens occurred as early as neutralizing antibodies were detected by the ppNT and earlier than antibodies were detected by the inactivated MERS-CoV and N-terminal domain (NTD) ELISAs. Antibodies detected by the NP ELISA occurred last. Strong correlations were found between the S1, RBD and NP ELISAs and the inactivated MERS-CoV ELISA. The S and RBD ELISAs were highly correlated with the commercial S1 ELISA. The S ELISA strongly correlated with the ppNT, although the MERS-CoV, S1, NTD and RBD ELISAs were also significantly correlated with the ppNT (P<0.001).",2016 Nov 9,"['Wang, Wenling', 'Wang, Huijuan', 'Deng, Yao', 'Song, Tie', 'Lan, Jiaming', 'Wu, Guizhen', 'Ke, Changwen', 'Tan, Wenjie']",Emerg Microbes Infect,,,False
3db2c3d613104b23711a28ea5f8f6a414d303376,PMC,Viral Agents Causing Acute Respiratory Infections in Children under Five: A Study from Eastern India,http://dx.doi.org/10.1155/2016/7235482,PMC5149672,28018433,CC BY,"Background. Acute respiratory infections (ARIs) are important cause of mortality and morbidity in children under five in developing country. Methods. This observational study was conducted over two-year period in a tertiary care teaching hospital of Eastern India. Nasal and throat swabs were collected, transported to the laboratory at 2–8°C in viral transport media, and then processed for detection of viruses using mono/multiplex real-time polymerase chain reaction. Results. A total of 300 children aged 2–60 months with ARIs were included. The most common age group affected with LRI was 2–12 mo and with URI was >12–60 mo. Viruses were detected in 248 cases. In URI, 77 were positive for single virus and 19 were positive for more than one virus; in LRI, 113 were positive for single virus and 12 were positive for more than one virus. The most common viruses isolated from URI cases were rhinovirus and adenovirus. The most common viruses isolated from LRI cases were respiratory syncytial virus and influenza virus. Most cases occurred in the months of January, December, and August. Conclusion. Viruses constitute a significant cause of ARI in children under five. RSV, ADV, RV, and IFV were the most prevalent viruses isolated.",2016 Nov 27,"['Mishra, Pravakar', 'Nayak, Lipika', 'Das, Rashmi Ranjan', 'Dwibedi, Bhagirathi', 'Singh, Amitabh']",Int J Pediatr,,,True
c9b4c7691175724573497c35ff6ac960a3208104,PMC,Glucose-6-phosphate dehydrogenase deficiency  (G6PD) as a risk factor of male neonatal sepsis,,PMC5152609,27974910,CC BY,"Introduction.Neonatal sepsis is a disease process, which represents the systemic response of bacteria entering the bloodstream during the first 28 days of life. The prevalence of sepsis is higher in male infants than in females, but the exact cause is unknown. Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the pentose phosphate pathway, which leads to the production of NADPH. NADPH is required for the respiratory burst reaction in white blood cells (WBCs) to destroy microorganisms. The purpose of this study was to evaluate the prevalence of G6PD deficiency in neonates with sepsis. Materials and methods.This study was performed on 76 neonates with sepsis and 1214 normal neonates from February 2012 to November 2014 in the west of Iran. The G6PD deficiency status was determined by fluorescent spot test. WBCs number and neutrophils percentages were measured and compared in patients with and without G6PD deficiency. Results.The prevalence of the G6PD deficiency in neonates with sepsis was significantly higher compared to the control group (p=0.03). WBCs number and neutrophils percentages in G6PD deficient patients compared with patients without G6PD deficiency were decreased, but were not statistically significant (p=0.77 and p=0.86 respectively). Conclusions.G6PD deficiency is a risk factor of neonatal sepsis and also a justification for more male involvement in this disease. Therefore, newborn screening for this disorder is recommended.",2016 Jan-Mar,"['Rostami-Far, Z', 'Ghadiri, K', 'Rostami-Far, M', 'Shaveisi-Zadeh, F', 'Amiri, A', 'Rahimian Zarif, B']",J Med Life,,,True
f787f681d002077ccf52bcea98f4e708d71fd41d,PMC,The Effect of Contact Investigations and Public Health Interventions in the Control and Prevention of Measles Transmission: A Simulation Study,http://dx.doi.org/10.1371/journal.pone.0167160,PMC5152814,27941976,CC BY,"BACKGROUND: Measles cases continue to occur despite its elimination status in the United States. To control transmission, public health officials confirm the measles diagnosis, identify close contacts of infectious cases, deliver public health interventions (i.e., post-exposure prophylaxis) among those who are eligible, and follow-up with the close contacts to determine overall health outcomes. A stochastic network simulation of measles contact tracing was conducted using existing agent-based modeling software and a synthetic population with high levels of immunity in order to estimate the impact of different interventions in controlling measles transmission. METHODS AND FINDINGS: The synthetic population was created to simulate California`s population in terms of population demographics, household, workplace, school, and neighborhood characteristics using California Department of Finance 2010 census data. Parameters for the model were obtained from a review of the literature, California measles case surveillance data, and expert opinion. Eight different scenarios defined by the use of three different public health interventions were evaluated: (a) post-exposure measles, mumps, and rubella (MMR) vaccine, (b) post-exposure immune globulin (IG), and (c) voluntary isolation and home quarantine in the presence or absence of public health response delays. Voluntary isolation and home quarantine coupled with one or two other interventions had the greatest reduction in the number of secondary cases infected by the index case and the probability of escape situations (i.e., the outbreak continues after 90 days). CONCLUSIONS: Interrupting contact patterns via voluntary isolation and home quarantine are particularly important in reducing the number of secondary cases infected by the index case and the probability of uncontrolled outbreaks.",2016 Dec 12,"['Enanoria, Wayne T. A.', 'Liu, Fengchen', 'Zipprich, Jennifer', 'Harriman, Kathleen', 'Ackley, Sarah', 'Blumberg, Seth', 'Worden, Lee', 'Porco, Travis C.']",PLoS One,,,True
814ecf9043112382eaae1310c6359ddc70557bba,PMC,Assessment of Ebola virus disease preparedness in the WHO South-East Asia Region,http://dx.doi.org/10.2471/BLT.16.174441,PMC5153931,27994284,CC BY,"OBJECTIVE: To conduct assessments of Ebola virus disease preparedness in countries of the World Health Organization (WHO) South-East Asia Region. METHODS: Nine of 11 countries in the region agreed to be assessed. During February to November 2015 a joint team from WHO and ministries of health conducted 4–5 day missions to Bangladesh, Bhutan, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand and Timor-Leste. We collected information through guided discussions with senior technical leaders and visits to hospitals, laboratories and airports. We assessed each country’s Ebola virus disease preparedness on 41 tasks under nine key components adapted from the WHO Ebola preparedness checklist of January 2015. FINDINGS: Political commitment to Ebola preparedness was high in all countries. Planning was most advanced for components that had been previously planned or tested for influenza pandemics: multilevel and multisectoral coordination; multidisciplinary rapid response teams; public communication and social mobilization; drills in international airports; and training on personal protective equipment. Major vulnerabilities included inadequate risk assessment and risk communication; gaps in data management and analysis for event surveillance; and limited capacity in molecular diagnostic techniques. Many countries had limited planning for a surge of Ebola cases. Other tasks needing improvement included: advice to inbound travellers; adequate isolation rooms; appropriate infection control practices; triage systems in hospitals; laboratory diagnostic capacity; contact tracing; and danger pay to staff to ensure continuity of care. CONCLUSION: Joint assessment and feedback about the functionality of Ebola virus preparedness systems help countries strengthen their core capacities to meet the International Health Regulations.",2016 Dec 1,"['Vong, Sirenda', 'Samuel, Reuben', 'Gould, Philip', 'El Sakka, Hammam', 'Rana, Bardan J', 'Pinyowiwat, Vason', 'Bezbaruah, Supriya', 'Ofrin, Roderico']",Bull World Health Organ,,,True
4ba9bd26567dc15bc9a0abf88342604d62e336ab,PMC,Assay optimization for molecular detection of Zika virus,http://dx.doi.org/10.2471/BLT.16.175950,PMC5153932,27994281,CC BY,"OBJECTIVE: To examine the diagnostic performance of real-time reverse transcription (RT)-polymerase chain reaction (PCR) assays for Zika virus detection. METHODS: We compared seven published real-time RT–PCR assays and two new assays that we have developed. To determine the analytical sensitivity of each assay, we constructed a synthetic universal control ribonucleic acid (uncRNA) containing all of the assays’ target regions on one RNA strand and spiked human blood or urine with known quantities of African or Asian Zika virus strains. Viral loads in 33 samples from Zika virus-infected patients were determined by using one of the new assays. FINDINGS: Oligonucleotides of the published real-time RT–PCR assays, showed up to 10 potential mismatches with the Asian lineage causing the current outbreak, compared with 0 to 4 mismatches for the new assays. The 95% lower detection limit of the seven most sensitive assays ranged from 2.1 to 12.1 uncRNA copies/reaction. Two assays had lower sensitivities of 17.0 and 1373.3 uncRNA copies/reaction and showed a similar sensitivity when using spiked samples. The mean viral loads in samples from Zika virus-infected patients were 5 × 10(4) RNA copies/mL of blood and 2 × 10(4) RNA copies/mL of urine. CONCLUSION: We provide reagents and updated protocols for Zika virus detection suitable for the current outbreak strains. Some published assays might be unsuitable for Zika virus detection, due to the limited sensitivity and potential incompatibility with some strains. Viral concentrations in the clinical samples were close to the technical detection limit, suggesting that the use of insensitive assays will cause false-negative results.",2016 Dec 1,"['Corman, Victor M', 'Rasche, Andrea', 'Baronti, Cecile', 'Aldabbagh, Souhaib', 'Cadar, Daniel', 'Reusken, Chantal BEM', 'Pas, Suzan D', 'Goorhuis, Abraham', 'Schinkel, Janke', 'Molenkamp, Richard', 'Kümmerer, Beate M', 'Bleicker, Tobias', 'Brünink, Sebastian', 'Eschbach-Bludau, Monika', 'Eis-Hübinger, Anna M', 'Koopmans, Marion P', 'Schmidt-Chanasit, Jonas', 'Grobusch, Martin P', 'de Lamballerie, Xavier', 'Drosten, Christian', 'Drexler, Jan Felix']",Bull World Health Organ,,,True
8029841b3e6b0267188b9c527b0e02dc472b9fdc,PMC,Single Fluorescence Channel-based Multiplex Detection of Avian Influenza Virus by Quantitative PCR with Intercalating Dye,http://dx.doi.org/10.1038/srep11479,PMC5155576,26088868,CC BY,"Since its invention in 1985 the polymerase chain reaction (PCR) has become a well-established method for amplification and detection of segments of double-stranded DNA. Incorporation of fluorogenic probe or DNA intercalating dyes (such as SYBR Green) into the PCR mixture allowed real-time reaction monitoring and extraction of quantitative information (qPCR). Probes with different excitation spectra enable multiplex qPCR of several DNA segments using multi-channel optical detection systems. Here we show multiplex qPCR using an economical EvaGreen-based system with single optical channel detection. Previously reported non quantitative multiplex real-time PCR techniques based on intercalating dyes were conducted once the PCR is completed by performing melting curve analysis (MCA). The technique presented in this paper is both qualitative and quantitative as it provides information about the presence of multiple DNA strands as well as the number of starting copies in the tested sample. Besides important internal control, multiplex qPCR also allows detecting concentrations of more than one DNA strand within the same sample. Detection of the avian influenza virus H7N9 by PCR is a well established method. Multiplex qPCR greatly enhances its specificity as it is capable of distinguishing both haemagglutinin (HA) and neuraminidase (NA) genes as well as their ratio.",2015 Jun 19,"['Ahberg, Christian D.', 'Manz, Andreas', 'Neuzil, Pavel']",Sci Rep,,,True
a274eabdee76dfe956dc3fdcaa5a105e8fd465bd,PMC,The ecology and adaptive evolution of influenza A interspecies transmission,http://dx.doi.org/10.1111/irv.12412,PMC5155642,27426214,CC BY,"Since 2013, there have been several alarming influenza‐related events; the spread of highly pathogenic avian influenza H5 viruses into North America, the detection of H10N8 and H5N6 zoonotic infections, the ongoing H7N9 infections in China and the continued zoonosis of H5N1 viruses in parts of Asia and the Middle East. The risk of a new influenza pandemic increases with the repeated interspecies transmission events that facilitate reassortment between animal influenza strains; thus, it is of utmost importance to understand the factors involved that promote or become a barrier to cross‐species transmission of Influenza A viruses (IAVs). Here, we provide an overview of the ecology and evolutionary adaptations of IAVs, with a focus on a review of the molecular factors that enable interspecies transmission of the various virus gene segments.",2017 Jan 8,"['Joseph, Udayan', 'Su, Yvonne C. F.', 'Vijaykrishna, Dhanasekaran', 'Smith, Gavin J. D.']",Influenza Other Respir Viruses,,,True
0c2489ea506fea5ac57b464c2a99f893cc867ff3,PMC,Epidemiology and clinical characteristics of respiratory syncytial virus infections among children and adults in Mexico,http://dx.doi.org/10.1111/irv.12414,PMC5155644,27439650,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is a leading etiological agent of acute respiratory tract infections and hospitalizations in children. However, little information is available regarding RSV infections in Latin American countries, particularly among adult patients. OBJECTIVE: To describe the epidemiology of RSV infection and to analyze the factors associated with severe infections in children and adults in Mexico. METHODS: Patients ≥1 month old, who presented with an influenza‐like illness (ILI) to six hospitals in Mexico, were eligible for participation in the study. Multiplex reverse‐transcriptase polymerase chain reaction identified viral pathogens in nasal swabs from 5629 episodes of ILI. Patients in whom RSV was detected were included in this report. RESULTS: Respiratory syncytial virus was detected in 399 children and 171 adults. RSV A was detected in 413 cases and RSV B in 163, including six patients who had coinfection with both subtypes; 414 (72.6%) patients required hospital admission, including 96 (16.8%) patients that required admission to the intensive care unit. Coinfection with one or more respiratory pathogens other than RSV was detected in 159 cases. Young age (in children) and older age (in adults) as well as the presence of some underlying conditions were associated with more severe disease. CONCLUSIONS: This study confirms that RSV is an important respiratory pathogen in children in Mexico. In addition, a substantial number of cases in adults were also detected highlighting the relevance of this virus in all ages. It is important to identify subjects at high risk of complications who may benefit from current or future preventive interventions.",2017 Jan 18,"['Gamiño‐Arroyo, Ana E.', 'Moreno‐Espinosa, Sarbelio', 'Llamosas‐Gallardo, Beatriz', 'Ortiz‐Hernández, Ana A.', 'Guerrero, M. Lourdes', 'Galindo‐Fraga, Arturo', 'Galán‐Herrera, Juan F.', 'Prado‐Galbarro, Francisco J.', 'Beigel, John H.', 'Ruiz‐Palacios, Guillermo M.', 'Noyola, Daniel E.', None]",Influenza Other Respir Viruses,,,True
2b84b189357f940efd105bcfe6e45ea14bdcc95c,PMC,CONSISE statement on the reporting of Seroepidemiologic Studies for influenza (ROSES‐I statement): an extension of the STROBE statement,http://dx.doi.org/10.1111/irv.12411,PMC5155648,27417916,CC BY,"BACKGROUND: Population‐based serologic studies are a vital tool for understanding the epidemiology of influenza and other respiratory viruses, including the early assessment of the transmissibility and severity of the 2009 influenza pandemic, and Middle East respiratory syndrome coronavirus. However, interpretation of the results of serologic studies has been hampered by the diversity of approaches and the lack of standardized methods and reporting. OBJECTIVE: The objective of the CONSISE ROSES ‐I statement was to improve the quality and transparency of reporting of influenza seroepidemiologic studies and facilitate the assessment of the validity and generalizability of published results. METHODS: The ROSES‐I statement was developed as an expert consensus of the CONSISE epidemiology and laboratory working groups. The recommendations are presented in the familiar format of a reporting guideline. Because seroepidemiologic studies are a specific type of observational epidemiology study, the ROSES‐I statement is built upon the STROBE guidelines. As such, the ROSES‐I statement should be seen as an extension of the STROBE guidelines. RESULTS: The ROSES ‐I statement presents 42 items that can be used as a checklist of the information that should be included in the results of published seroepidemiologic studies, and which can also serve as a guide to the items that need to be considered during study design and implementation. CONCLUSIONS: We hope that the ROSES‐I statement will contribute to improving the quality of reporting of seroepidemiologic studies.",2017 Jan 9,"['Horby, Peter W.', 'Laurie, Karen L.', 'Cowling, Benjamin J.', 'Engelhardt, Othmar G.', 'Sturm‐Ramirez, Katharine', 'Sanchez, Jose L.', 'Katz, Jacqueline M.', 'Uyeki, Timothy M.', 'Wood, John', 'Van Kerkhove, Maria D.', None]",Influenza Other Respir Viruses,,,True
7bc3103f71aaffbda7cdeb61603f12ded3194ab5,PMC,Cross‐sectional survey and surveillance for influenza viruses and MERS‐CoV among Egyptian pilgrims returning from Hajj during 2012‐2015,http://dx.doi.org/10.1111/irv.12429,PMC5155725,27603034,CC BY,"BACKGROUND: Approximately 80 000 Egyptians participate in Hajj pilgrimage annually. The purpose of this study was to estimate influenza virus and MERS‐CoV prevalence among Egyptian pilgrims returning from Hajj. STUDY: A cross‐sectional survey among 3 364 returning Egyptian pilgrims from 2012 to 2015 was conducted. Nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected from all participants. Sputum specimens were collected from participants with respiratory symptoms and productive cough at the time of their interview. Specimens were tested for influenza viruses, and a convenience sample of NP/OP specimens was tested for MERS‐CoV. Thirty percent of participants met the case definition for influenza‐like illness (ILI), 14% tested positive for influenza viruses, and none tested positive for MERS‐CoV. Self‐reported influenza vaccination was 20%. CONCLUSIONS: High prevalence of reported ILI during pilgrimage and confirmed influenza virus on return from pilgrimage suggest a continued need for influenza prevention strategies for Egyptian Hajj pilgrims. An evaluation of the Ministry of Health and Population's current risk communication campaigns to increase influenza vaccine use among pilgrims may help identify strategies to improve vaccine coverage.",2017 Jan 11,"['Refaey, Samir', 'Amin, Marwa Mohamed', 'Roguski, Katherine', 'Azziz‐Baumgartner, Eduardo', 'Uyeki, Timothy M.', 'Labib, Manal', 'Kandeel, Amr']",Influenza Other Respir Viruses,,,True
788295abb7003fc90fdadb54283b664724c83b33,PMC,The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/mBio.01721-16,PMC5156301,27965448,CC BY,"ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity in vitro. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.",2016 Dec 13,"['Fehr, Anthony R.', 'Channappanavar, Rudragouda', 'Jankevicius, Gytis', 'Fett, Craig', 'Zhao, Jincun', 'Athmer, Jeremiah', 'Meyerholz, David K.', 'Ahel, Ivan', 'Perlman, Stanley']",mBio,,,True
49e8d990cb97517904b72c77aa457ee4564e6779,PMC,The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/mBio.01721-16,PMC5156301,27965448,CC BY,"ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity in vitro. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.",2016 Dec 13,"['Fehr, Anthony R.', 'Channappanavar, Rudragouda', 'Jankevicius, Gytis', 'Fett, Craig', 'Zhao, Jincun', 'Athmer, Jeremiah', 'Meyerholz, David K.', 'Ahel, Ivan', 'Perlman, Stanley']",mBio,,,False
76ac304a8bf37f61466085482cee345aae6dd1f4,PMC,The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/mBio.01721-16,PMC5156301,27965448,CC BY,"ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity in vitro. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.",2016 Dec 13,"['Fehr, Anthony R.', 'Channappanavar, Rudragouda', 'Jankevicius, Gytis', 'Fett, Craig', 'Zhao, Jincun', 'Athmer, Jeremiah', 'Meyerholz, David K.', 'Ahel, Ivan', 'Perlman, Stanley']",mBio,,,False
24ffda519bebb75d54ef12eea8759ca4be138262,PMC,The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/mBio.01721-16,PMC5156301,27965448,CC BY,"ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity in vitro. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.",2016 Dec 13,"['Fehr, Anthony R.', 'Channappanavar, Rudragouda', 'Jankevicius, Gytis', 'Fett, Craig', 'Zhao, Jincun', 'Athmer, Jeremiah', 'Meyerholz, David K.', 'Ahel, Ivan', 'Perlman, Stanley']",mBio,,,False
a15edc2d862771e530d404425b5910b328857db9,PMC,The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/mBio.01721-16,PMC5156301,27965448,CC BY,"ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity in vitro. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.",2016 Dec 13,"['Fehr, Anthony R.', 'Channappanavar, Rudragouda', 'Jankevicius, Gytis', 'Fett, Craig', 'Zhao, Jincun', 'Athmer, Jeremiah', 'Meyerholz, David K.', 'Ahel, Ivan', 'Perlman, Stanley']",mBio,,,False
6ac1bb3e9bac1d430c9d492be6664a9443e52cea,PMC,The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/mBio.01721-16,PMC5156301,27965448,CC BY,"ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity in vitro. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.",2016 Dec 13,"['Fehr, Anthony R.', 'Channappanavar, Rudragouda', 'Jankevicius, Gytis', 'Fett, Craig', 'Zhao, Jincun', 'Athmer, Jeremiah', 'Meyerholz, David K.', 'Ahel, Ivan', 'Perlman, Stanley']",mBio,,,False
494420ff931d8a803437b8830be805b57db29969,PMC,The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/mBio.01721-16,PMC5156301,27965448,CC BY,"ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity in vitro. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.",2016 Dec 13,"['Fehr, Anthony R.', 'Channappanavar, Rudragouda', 'Jankevicius, Gytis', 'Fett, Craig', 'Zhao, Jincun', 'Athmer, Jeremiah', 'Meyerholz, David K.', 'Ahel, Ivan', 'Perlman, Stanley']",mBio,,,False
5a073b51c60bf4d599c2e5bfe236bd11abf07daa,PMC,Foot-and-mouth disease virus replicates independently of phosphatidylinositol 4-phosphate and type III phosphatidylinositol 4-kinases,http://dx.doi.org/10.1099/jgv.0.000485,PMC5156328,27093462,CC BY,"Picornaviruses form replication complexes in association with membranes in structures called replication organelles. Common themes to emerge from studies of picornavirus replication are the need for cholesterol and phosphatidylinositol 4-phosphate (PI4P). In infected cells, type III phosphatidylinositol 4-kinases (PI4KIIIs) generate elevated levels of PI4P, which is then exchanged for cholesterol at replication organelles. For the enteroviruses, replication organelles form at Golgi membranes in a process that utilizes PI4KIIIβ. Other picornaviruses, for example the cardioviruses, are believed to initiate replication at the endoplasmic reticulum and subvert PI4KIIIα to generate PI4P. Here we investigated the role of PI4KIII in foot-and-mouth disease virus (FMDV) replication. Our results showed that, in contrast to the enteroviruses and the cardioviruses, FMDV replication does not require PI4KIII (PI4KIIIα and PI4KIIIβ), and PI4P levels do not increase in FMDV-infected cells and PI4P is not seen at replication organelles. These results point to a unique requirement towards lipids at the FMDV replication membranes.",2016 Aug,"['Berryman, Stephen', 'Moffat, Katy', 'Harak, Christian', 'Lohmann, Volker', 'Jackson, Terry']",J Gen Virol,,,True
9978c4e80ad9c6c31863571080b871eb4c412168,PMC,Foot-and-mouth disease virus replicates independently of phosphatidylinositol 4-phosphate and type III phosphatidylinositol 4-kinases,http://dx.doi.org/10.1099/jgv.0.000485,PMC5156328,27093462,CC BY,"Picornaviruses form replication complexes in association with membranes in structures called replication organelles. Common themes to emerge from studies of picornavirus replication are the need for cholesterol and phosphatidylinositol 4-phosphate (PI4P). In infected cells, type III phosphatidylinositol 4-kinases (PI4KIIIs) generate elevated levels of PI4P, which is then exchanged for cholesterol at replication organelles. For the enteroviruses, replication organelles form at Golgi membranes in a process that utilizes PI4KIIIβ. Other picornaviruses, for example the cardioviruses, are believed to initiate replication at the endoplasmic reticulum and subvert PI4KIIIα to generate PI4P. Here we investigated the role of PI4KIII in foot-and-mouth disease virus (FMDV) replication. Our results showed that, in contrast to the enteroviruses and the cardioviruses, FMDV replication does not require PI4KIII (PI4KIIIα and PI4KIIIβ), and PI4P levels do not increase in FMDV-infected cells and PI4P is not seen at replication organelles. These results point to a unique requirement towards lipids at the FMDV replication membranes.",2016 Aug,"['Berryman, Stephen', 'Moffat, Katy', 'Harak, Christian', 'Lohmann, Volker', 'Jackson, Terry']",J Gen Virol,,,False
7f2079d6e5244be0e38c55fe08a1c1672ab645fb,PMC,Viral factors in influenza pandemic risk assessment,http://dx.doi.org/10.7554/eLife.18491,PMC5156527,27834632,CC0,"The threat of an influenza A virus pandemic stems from continual virus spillovers from reservoir species, a tiny fraction of which spark sustained transmission in humans. To date, no pandemic emergence of a new influenza strain has been preceded by detection of a closely related precursor in an animal or human. Nonetheless, influenza surveillance efforts are expanding, prompting a need for tools to assess the pandemic risk posed by a detected virus. The goal would be to use genetic sequence and/or biological assays of viral traits to identify those non-human influenza viruses with the greatest risk of evolving into pandemic threats, and/or to understand drivers of such evolution, to prioritize pandemic prevention or response measures. We describe such efforts, identify progress and ongoing challenges, and discuss three specific traits of influenza viruses (hemagglutinin receptor binding specificity, hemagglutinin pH of activation, and polymerase complex efficiency) that contribute to pandemic risk. DOI: http://dx.doi.org/10.7554/eLife.18491.001",,"['Lipsitch, Marc', 'Barclay, Wendy', 'Raman, Rahul', 'Russell, Charles J', 'Belser, Jessica A', 'Cobey, Sarah', 'Kasson, Peter M', 'Lloyd-Smith, James O', 'Maurer-Stroh, Sebastian', 'Riley, Steven', 'Beauchemin, Catherine AA', 'Bedford, Trevor', 'Friedrich, Thomas C', 'Handel, Andreas', 'Herfst, Sander', 'Murcia, Pablo R', 'Roche, Benjamin', 'Wilke, Claus O', 'Russell, Colin A']",eLife.; 5:e18491,,,True
3455e9fd57dea013498de20c236c15b7bf19b424,PMC,A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses,http://dx.doi.org/10.1128/mSphere.00275-16,PMC5156671,27981236,CC BY,"The H1 subtype of influenza A viruses (IAVs) has been circulating in swine since the 1918 human influenza pandemic. Over time, and aided by further introductions from nonswine hosts, swine H1 viruses have diversified into three genetic lineages. Due to limited global data, these H1 lineages were named based on colloquial context, leading to a proliferation of inconsistent regional naming conventions. In this study, we propose rigorous phylogenetic criteria to establish a globally consistent nomenclature of swine H1 virus hemagglutinin (HA) evolution. These criteria applied to a data set of 7,070 H1 HA sequences led to 28 distinct clades as the basis for the nomenclature. We developed and implemented a web-accessible annotation tool that can assign these biologically informative categories to new sequence data. The annotation tool assigned the combined data set of 7,070 H1 sequences to the correct clade more than 99% of the time. Our analyses indicated that 87% of the swine H1 viruses from 2010 to the present had HAs that belonged to 7 contemporary cocirculating clades. Our nomenclature and web-accessible classification tool provide an accurate method for researchers, diagnosticians, and health officials to assign clade designations to HA sequences. The tool can be updated readily to track evolving nomenclature as new clades emerge, ensuring continued relevance. A common global nomenclature facilitates comparisons of IAVs infecting humans and pigs, within and between regions, and can provide insight into the diversity of swine H1 influenza virus and its impact on vaccine strain selection, diagnostic reagents, and test performance, thereby simplifying communication of such data. IMPORTANCE A fundamental goal in the biological sciences is the definition of groups of organisms based on evolutionary history and the naming of those groups. For influenza A viruses (IAVs) in swine, understanding the hemagglutinin (HA) genetic lineage of a circulating strain aids in vaccine antigen selection and allows for inferences about vaccine efficacy. Previous reporting of H1 virus HA in swine relied on colloquial names, frequently with incriminating and stigmatizing geographic toponyms, making comparisons between studies challenging. To overcome this, we developed an adaptable nomenclature using measurable criteria for historical and contemporary evolutionary patterns of H1 global swine IAVs. We also developed a web-accessible tool that classifies viruses according to this nomenclature. This classification system will aid agricultural production and pandemic preparedness through the identification of important changes in swine IAVs and provides terminology enabling discussion of swine IAVs in a common context among animal and human health initiatives.",2016 Dec 14,"['Anderson, Tavis K.', 'Macken, Catherine A.', 'Lewis, Nicola S.', 'Scheuermann, Richard H.', 'Van Reeth, Kristien', 'Brown, Ian H.', 'Swenson, Sabrina L.', 'Simon, Gaëlle', 'Saito, Takehiko', 'Berhane, Yohannes', 'Ciacci-Zanella, Janice', 'Pereda, Ariel', 'Davis, C. Todd', 'Donis, Ruben O.', 'Webby, Richard J.', 'Vincent, Amy L.']",mSphere,,,True
36752c93b63eeae6c380c8fa56aa2080b695830c,PMC,Porcine Epidemic Diarrhea Virus Shedding and Antibody Response in Swine Farms: A Longitudinal Study,http://dx.doi.org/10.3389/fmicb.2016.02009,PMC5156881,28018330,CC BY,"The porcine epidemic diarrhea virus (PEDV) causes an acute and highly contagious enteric disease characterized by severe enteritis, vomiting, watery diarrhea, and a high mortality rate in seronegative neonatal piglets. In the last few years, PED had a large economic impact on the swine industries in Asia and the US, and in 2014, the PEDV also re-emerged in Europe. Two main PEDV variants circulate worldwide but only the S INDEL variant, considered a mild strain, is spreading in Europe. To gain insights into the pathogenicity of this variant, its viral load and temporal shedding pattern were evaluated in piglets from infected farms. Quantitative real-time PCR (qPCR) targeting the spike gene, was validated according to the minimum information for quantitative real-time PCR experiments guidelines. The qPCR was applied to longitudinal studies conducted in four swine farms naturally infected with the PEDV S INDEL variant. Clinical data, fecal swabs, and blood samples were collected from 103 piglets at 15–30-day intervals for 2–5 months. On all four farms, diarrhea was observed in sows during gestation and in farrowing units, and the mortality rates of piglets were 18, 25, 30, and 35%. Different clinical pictures (0-50% of diarrhea positivity), viral titer levels (mean 5.3-7.2 log(10) genome copies/mL), and antibody conditions (30-80% of positivity) were registered among sows on the four farms. The percentage of qPCR positive piglets varied greatly from the beginning (63–100%) to the end (0%) of the infection course. Clinical signs were present in 96% of the qPCR positive animals. Viral loads ranged from 8.5 log(10) to 4 log(10) genome copies/mL in suckling pigs at 3–6 days of age and were not statistically different among farms, despite the different patterns observed in sows. After 2–3 weeks, only a few piglets still showed detectable viral levels and clinical signs, and they developed antibody responses. Moreover, co-infections with other pathogens and biosecurity procedures limiting the circulation of the virus could have influenced the severity of PED infection. QPCR and clinical data were useful in understanding the dynamics of PEDV infections and, therefore, in implementing appropriate control measures.",2016 Dec 15,"['Bertasio, Cristina', 'Giacomini, Enrico', 'Lazzaro, Massimiliano', 'Perulli, Simona', 'Papetti, Alice', 'Lavazza, Antonio', 'Lelli, Davide', 'Alborali, Giovanni', 'Boniotti, Maria B.']",Front Microbiol,,,False
2f19514c3e82b60132c6170ba732029ade5827a2,PMC,Porcine Epidemic Diarrhea Virus Shedding and Antibody Response in Swine Farms: A Longitudinal Study,http://dx.doi.org/10.3389/fmicb.2016.02009,PMC5156881,28018330,CC BY,"The porcine epidemic diarrhea virus (PEDV) causes an acute and highly contagious enteric disease characterized by severe enteritis, vomiting, watery diarrhea, and a high mortality rate in seronegative neonatal piglets. In the last few years, PED had a large economic impact on the swine industries in Asia and the US, and in 2014, the PEDV also re-emerged in Europe. Two main PEDV variants circulate worldwide but only the S INDEL variant, considered a mild strain, is spreading in Europe. To gain insights into the pathogenicity of this variant, its viral load and temporal shedding pattern were evaluated in piglets from infected farms. Quantitative real-time PCR (qPCR) targeting the spike gene, was validated according to the minimum information for quantitative real-time PCR experiments guidelines. The qPCR was applied to longitudinal studies conducted in four swine farms naturally infected with the PEDV S INDEL variant. Clinical data, fecal swabs, and blood samples were collected from 103 piglets at 15–30-day intervals for 2–5 months. On all four farms, diarrhea was observed in sows during gestation and in farrowing units, and the mortality rates of piglets were 18, 25, 30, and 35%. Different clinical pictures (0-50% of diarrhea positivity), viral titer levels (mean 5.3-7.2 log(10) genome copies/mL), and antibody conditions (30-80% of positivity) were registered among sows on the four farms. The percentage of qPCR positive piglets varied greatly from the beginning (63–100%) to the end (0%) of the infection course. Clinical signs were present in 96% of the qPCR positive animals. Viral loads ranged from 8.5 log(10) to 4 log(10) genome copies/mL in suckling pigs at 3–6 days of age and were not statistically different among farms, despite the different patterns observed in sows. After 2–3 weeks, only a few piglets still showed detectable viral levels and clinical signs, and they developed antibody responses. Moreover, co-infections with other pathogens and biosecurity procedures limiting the circulation of the virus could have influenced the severity of PED infection. QPCR and clinical data were useful in understanding the dynamics of PEDV infections and, therefore, in implementing appropriate control measures.",2016 Dec 15,"['Bertasio, Cristina', 'Giacomini, Enrico', 'Lazzaro, Massimiliano', 'Perulli, Simona', 'Papetti, Alice', 'Lavazza, Antonio', 'Lelli, Davide', 'Alborali, Giovanni', 'Boniotti, Maria B.']",Front Microbiol,,,False
68c82e3e364e4f32d14a480538ccc8d0b5d5802c,PMC,Porcine Epidemic Diarrhea Virus Shedding and Antibody Response in Swine Farms: A Longitudinal Study,http://dx.doi.org/10.3389/fmicb.2016.02009,PMC5156881,28018330,CC BY,"The porcine epidemic diarrhea virus (PEDV) causes an acute and highly contagious enteric disease characterized by severe enteritis, vomiting, watery diarrhea, and a high mortality rate in seronegative neonatal piglets. In the last few years, PED had a large economic impact on the swine industries in Asia and the US, and in 2014, the PEDV also re-emerged in Europe. Two main PEDV variants circulate worldwide but only the S INDEL variant, considered a mild strain, is spreading in Europe. To gain insights into the pathogenicity of this variant, its viral load and temporal shedding pattern were evaluated in piglets from infected farms. Quantitative real-time PCR (qPCR) targeting the spike gene, was validated according to the minimum information for quantitative real-time PCR experiments guidelines. The qPCR was applied to longitudinal studies conducted in four swine farms naturally infected with the PEDV S INDEL variant. Clinical data, fecal swabs, and blood samples were collected from 103 piglets at 15–30-day intervals for 2–5 months. On all four farms, diarrhea was observed in sows during gestation and in farrowing units, and the mortality rates of piglets were 18, 25, 30, and 35%. Different clinical pictures (0-50% of diarrhea positivity), viral titer levels (mean 5.3-7.2 log(10) genome copies/mL), and antibody conditions (30-80% of positivity) were registered among sows on the four farms. The percentage of qPCR positive piglets varied greatly from the beginning (63–100%) to the end (0%) of the infection course. Clinical signs were present in 96% of the qPCR positive animals. Viral loads ranged from 8.5 log(10) to 4 log(10) genome copies/mL in suckling pigs at 3–6 days of age and were not statistically different among farms, despite the different patterns observed in sows. After 2–3 weeks, only a few piglets still showed detectable viral levels and clinical signs, and they developed antibody responses. Moreover, co-infections with other pathogens and biosecurity procedures limiting the circulation of the virus could have influenced the severity of PED infection. QPCR and clinical data were useful in understanding the dynamics of PEDV infections and, therefore, in implementing appropriate control measures.",2016 Dec 15,"['Bertasio, Cristina', 'Giacomini, Enrico', 'Lazzaro, Massimiliano', 'Perulli, Simona', 'Papetti, Alice', 'Lavazza, Antonio', 'Lelli, Davide', 'Alborali, Giovanni', 'Boniotti, Maria B.']",Front Microbiol,,,True
92af993d895fbe5ec7c8ba631624b1a66171a7c8,PMC,Screening and Identification of APOC1 as a Novel Potential Biomarker for Differentiate of Mycoplasma pneumoniae in Children,http://dx.doi.org/10.3389/fmicb.2016.01961,PMC5156883,28018301,CC BY,"Background: Although Mycoplasma pneumoniae (MP) is a common cause of community-acquired pneumonia (CAP) in children, the currently used diagnostic methods are not optimal. Proteomics is increasingly being used to study the biomarkers of infectious diseases. Methods: Label-free quantitative proteomics and liquid chromatography-mass/mass spectrometry were used to analyze the fold change of protein expression in plasma of children with MP pneumonia (MPP), infectious disease control (IDC), and healthy control (HC) groups. Selected proteins that can distinguish MPP from HC and IDC were further validated by enzyme-linked immunosorbent assay (ELISA). Results: After multivariate analyses, 27 potential plasma biomarkers were identified to be expressed differently among child MPP, HC, and IDC groups. Among these proteins, SERPINA3, APOC1, ANXA6, KNTC1, and CFLAR were selected for ELISA verification. SERPINA3, APOC1, and CFLAR levels were significantly different among the three groups and the ratios were consistent with the trends of proteomics results. A comparison of MPP patients and HC showed APOC1 had the largest area under the curve (AUC) of 0.853, with 77.6% sensitivity and 81.1% specificity. When APOC1 levels were compared between MPP and IDC patients, it also showed a relatively high AUC of 0.882, with 77.6% sensitivity and 85.3% specificity. Conclusion: APOC1 is a potential biomarker for the rapid and noninvasive diagnosis of MPP in children. The present finding may offer new insights into the pathogenesis and biomarker selection of MPP in children.",2016 Dec 15,"['Li, Jieqiong', 'Sun, Lin', 'Xu, Fang', 'Qi, Hui', 'Shen, Chen', 'Jiao, Weiwei', 'Xiao, Jing', 'Li, Qinjing', 'Xu, Baoping', 'Shen, Adong']",Front Microbiol,,,True
2c332ca9f08d552ef49e6945655e9059e82ba13d,PMC,Expression Cloning and Production of Human Heavy-Chain-Only Antibodies from Murine Transgenic Plasma Cells,http://dx.doi.org/10.3389/fimmu.2016.00619,PMC5165034,28066429,CC BY,"Several technologies have been developed to isolate human antibodies against different target antigens as a source of potential therapeutics, including hybridoma technology, phage and yeast display systems. For conventional antibodies, this involves either random pairing of VH and variable light (VL) domains in combinatorial display libraries or isolation of cognate pairs of VH and VL domains from human B cells or from transgenic mice carrying human immunoglobulin loci followed by single-cell sorting, single-cell RT-PCR, and bulk cloning of isolated natural VH–VL pairs. Heavy-chain-only antibodies (HCAbs) that naturally occur in camelids require only heavy immunoglobulin chain cloning. Here, we present an automatable novel, high-throughput technology for rapid direct cloning and production of fully human HCAbs from sorted population of transgenic mouse plasma cells carrying a human HCAb locus. Utility of the technique is demonstrated by isolation of diverse sets of sequence unique, soluble, high-affinity influenza A strain X-31 hemagglutinin-specific HCAbs.",2016 Dec 19,"['Drabek, Dubravka', 'Janssens, Rick', 'de Boer, Ernie', 'Rademaker, Rik', 'Kloess, Johannes', 'Skehel, John', 'Grosveld, Frank']",Front Immunol,,,True
5dc1559b4274012d8152b7c5f4ca0d637e8b62fa,PMC,Modernising epidemic science: enabling patient-centred research during epidemics,http://dx.doi.org/10.1186/s12916-016-0760-x,PMC5165716,27989237,CC BY,"BACKGROUND: Emerging and epidemic infectious disease outbreaks are a significant public health problem and global health security threat. As an outbreak begins, epidemiological investigations and traditional public health responses are generally mounted very quickly. However, patient-centred research is usually not prioritised when planning and enacting the response. Instead, the clinical research response occurs subsequent to and separate from the public health response, and is inadequate for evidence-based decision-making at the bedside or in the offices of public health policymakers. DISCUSSION: The deficiencies of the clinical research response to severe acute respiratory syndrome, pandemic influenza, Middle East respiratory syndrome coronavirus and Ebola virus demonstrate that current research models do not adequately inform and improve the quality of clinical care or public health response. Three suggestions for improvements are made. First, integrate the data and sample collection needs for clinical and public health decision-making within a unified framework, combined with a risk-based, rather than a discipline-based, approach to ethical review and consent. Second, develop clinical study methods and tools that are specifically designed to meet the epidemiological and contextual challenges of emerging and epidemic infectious diseases. Third, invest in investigator-led clinical research networks that are primed and incentivised to respond to outbreak infections, and which can call on the support and resources of a central centre of excellence. CONCLUSIONS: It is crucial that the field of epidemic science matures to place patients at the heart of the response. This can only be achieved when patient-centred research is integrated in the outbreak response from day one and practical steps are taken to reduce the barriers to the generation of reliable and useful evidence.",2016 Dec 19,"['Rojek, Amanda M.', 'Horby, Peter W.']",BMC Med,,,True
31ce4647dd3ce32716212b10cfa8b05724dc32fd,PMC,The Identification and Characterization of Two Novel Epitopes on the Nucleocapsid Protein of the Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.1038/srep39010,PMC5171872,27991537,CC BY,"Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe diarrhea and death, particularly in neonatal piglets. The nucleocapsid protein (N protein) of PEDV presents strong immunogenicity and contributes to the cross-reactivity between PEDV and TGEV. However, the characterization of epitopes on the PEDV N protein remains largely unknown. Here, two monoclonal antibodies (MAbs) specific to the N protein of a PEDV strain, FJzz1/2011, were generated and screened against a partially overlapping library of 24 GST-fusion N protein-truncated constructs. We confirmed that residues 18–133 (designated NEP-D4) and residues 252–262 (designated NEP-D6) were the epitopes targeted by MAbs PN-D4 and PN-D6, respectively. Sequence analysis revealed that these two epitopes were highly conserved among PEDV strains but were significantly different from other members of the Coronavirinae subfamily. Western blot analysis showed that they could be specifically recognized by PEDV antisera but could not be recognized by TGEV hyperimmune antisera. Indirect immunofluorescence (IFA) assays confirmed no cross-reaction between these two MAbs and TGEV. In addition, the freeze-thaw cycle and protease treatment results indicated that NEP-D4 was intrinsically disordered. All these results suggest that these two novel epitopes and their cognate MAbs could serve as the basis for the development of precise diagnostic assays for PEDV.",2016 Dec 19,"['Wang, Kang', 'Xie, Chun', 'Zhang, Jianan', 'Zhang, Wenchao', 'Yang, Deqiang', 'Yu, Lingxue', 'Jiang, Yifeng', 'Yang, Shen', 'Gao, Fei', 'Yang, Zhibiao', 'Zhou, Yanjun', 'Tong, Guangzhi']",Sci Rep,,,True
a3f75f7f759c60426c7a47b9cd2470a70ef244c0,PMC,Nonstructural Protein 11 of Porcine Reproductive and Respiratory Syndrome Virus Suppresses Both MAVS and RIG-I Expression as One of the Mechanisms to Antagonize Type I Interferon Production,http://dx.doi.org/10.1371/journal.pone.0168314,PMC5172586,27997564,CC BY,"Type I interferons (IFN-α/β) play a key role in antiviral defense, and porcine reproductive and respiratory syndrome virus (PRRSV) is known to down-regulate the IFN response in virus-infected cells and pigs. In this study, we showed that the overexpression of nsp11 of PRRSV induced a strong suppression of IFN production. Nsp11 suppressed both IRF3 and NF-κB activities when stimulated with a dsRNA analogue and TNF-α, respectively. This suppression was RLR dependent, since the transcripts and proteins of MAVS and RIG-I, two critical factors in RLR-mediated pathway, were both found to be reduced in the presence of overexpressed nsp11. Since nsp11 is an endoribonuclease (EndoU), the structure function relationship was examined using a series of nsp11 EndoU mutant plasmids. The mutants that impaired the EndoU activity failed to suppress IFN and led to the normal expression of MAVS. Seven single amino acid substitutions (4 in subdomain A and 3 in subdomain B) plus one insertion (frame-shift in nsp11) were then introduced into PRRSV infectious cDNA clones to generate nsp11 mutant viruses. Unfortunately, all EndoU knock-out nsp11 mutant viruses appeared replication-defective and no progenies were produced. Three mutations in EndoU subdomain A expressed the N and nsp2/3 proteins but their infectivity diminished after 2 passages. Taken together, our data show that PRRSV nsp11 endoribonuclease activity is critical for both viral replication and IFN antagonism. More importantly, the endoribonuclease activity of nsp11 demonstrates the substrate specificity towards MAVS and RIG-I (transcripts and proteins) over p65 and IRF3 in the context of gene transfection and overexpression. This is likely a mechanism of nsp11 suppression of type I IFN production.",2016 Dec 20,"['Sun, Yan', 'Ke, Hanzhong', 'Han, Mingyuan', 'Chen, Ning', 'Fang, Weihuan', 'Yoo, Dongwan']",PLoS One,,,True
26bdc177821e0161d138236656dafefe2f9f6900,PMC,Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection,http://dx.doi.org/10.1186/1471-2121-5-32,PMC517494,15333144,CC BY,"BACKGROUND: Viruses are obligate intracellular parasites and rely upon the host cell for different steps in their life cycles. The characterization of cellular genes required for virus infection and/or cell killing will be essential for understanding viral life cycles, and may provide cellular targets for new antiviral therapies. RESULTS: A gene entrapment approach was used to identify candidate cellular genes that affect reovirus infection or virus induced cell lysis. Four of the 111 genes disrupted in clones selected for resistance to infection by reovirus type 1 involved the insulin growth factor-2 (IGF-II) pathway, including: the mannose-6-phosphate/IGF2 receptor (Igf2r), a protease associated with insulin growth factor binding protein 5 (Prss11), and the CTCF transcriptional regulator (Ctcf). The disruption of Ctcf, which encodes a repressor of Igf2, was associated with enhanced Igf2 gene expression. Plasmids expressing either the IGF-II pro-hormone or IGF-II without the carboxy terminal extension (E)-peptide sequence independently conferred high levels of cellular resistance to reovirus infection. Forced IGF-II expression results in a block in virus disassembly. In addition, Ctcf disruption and forced Igf2 expression both enabled cells to proliferate in soft agar, a phenotype associated with malignant growth in vivo. CONCLUSION: These results indicate that IGF-II, and by inference other components of the IGF-II signalling pathway, can confer resistance to lytic reovirus infection. This report represents the first use of gene entrapment to identify host factors affecting virus infection. Concomitant transformation observed in some virus resistant cells illustrates a potential mechanism of carcinogenesis associated with chronic virus infection.",2004 Aug 27,"['Sheng, Jinsong', 'Organ, Edward L', 'Hao, Chuanming', 'Wells, K Sam', 'Ruley, H Earl', 'Rubin, Donald H']",BMC Cell Biol,,,True
626e2623bbb406b7fc1bd5b1da3ff4eb30e3888c,PMC,Mechanical unfolding kinetics of the SRV-1 gag-pro mRNA pseudoknot: possible implications for −1 ribosomal frameshifting stimulation,http://dx.doi.org/10.1038/srep39549,PMC5175198,28000744,CC BY,"Minus-one ribosomal frameshifting is a translational recoding mechanism widely utilized by many RNA viruses to generate accurate ratios of structural and catalytic proteins. An RNA pseudoknot structure located in the overlapping region of the gag and pro genes of Simian Retrovirus type 1 (SRV-1) stimulates frameshifting. However, the experimental characterization of SRV-1 pseudoknot (un)folding dynamics and the effect of the base triple formation is lacking. Here, we report the results of our single-molecule nanomanipulation using optical tweezers and theoretical simulation by steered molecular dynamics. Our results directly reveal that the energetic coupling between loop 2 and stem 1 via minor-groove base triple formation enhances the mechanical stability. The terminal base pair in stem 1 (directly in contact with a translating ribosome at the slippery site) also affects the mechanical stability of the pseudoknot. The −1 frameshifting efficiency is positively correlated with the cooperative one-step unfolding force and inversely correlated with the one-step mechanical unfolding rate at zero force. A significantly improved correlation was observed between −1 frameshifting efficiency and unfolding rate at forces of 15–35 pN, consistent with the fact that the ribosome is a force-generating molecular motor with helicase activity. No correlation was observed between thermal stability and −1 frameshifting efficiency.",2016 Dec 21,"['Zhong, Zhensheng', 'Yang, Lixia', 'Zhang, Haiping', 'Shi, Jiahao', 'Vandana, J. Jeya', 'Lam, Do Thuy Uyen Ha', 'Olsthoorn, René C. L.', 'Lu, Lanyuan', 'Chen, Gang']",Sci Rep,,,True
cd97d6b4e0495ffd6543a25ac01e843b8efa6b6c,PMC,Mechanical unfolding kinetics of the SRV-1 gag-pro mRNA pseudoknot: possible implications for −1 ribosomal frameshifting stimulation,http://dx.doi.org/10.1038/srep39549,PMC5175198,28000744,CC BY,"Minus-one ribosomal frameshifting is a translational recoding mechanism widely utilized by many RNA viruses to generate accurate ratios of structural and catalytic proteins. An RNA pseudoknot structure located in the overlapping region of the gag and pro genes of Simian Retrovirus type 1 (SRV-1) stimulates frameshifting. However, the experimental characterization of SRV-1 pseudoknot (un)folding dynamics and the effect of the base triple formation is lacking. Here, we report the results of our single-molecule nanomanipulation using optical tweezers and theoretical simulation by steered molecular dynamics. Our results directly reveal that the energetic coupling between loop 2 and stem 1 via minor-groove base triple formation enhances the mechanical stability. The terminal base pair in stem 1 (directly in contact with a translating ribosome at the slippery site) also affects the mechanical stability of the pseudoknot. The −1 frameshifting efficiency is positively correlated with the cooperative one-step unfolding force and inversely correlated with the one-step mechanical unfolding rate at zero force. A significantly improved correlation was observed between −1 frameshifting efficiency and unfolding rate at forces of 15–35 pN, consistent with the fact that the ribosome is a force-generating molecular motor with helicase activity. No correlation was observed between thermal stability and −1 frameshifting efficiency.",2016 Dec 21,"['Zhong, Zhensheng', 'Yang, Lixia', 'Zhang, Haiping', 'Shi, Jiahao', 'Vandana, J. Jeya', 'Lam, Do Thuy Uyen Ha', 'Olsthoorn, René C. L.', 'Lu, Lanyuan', 'Chen, Gang']",Sci Rep,,,True
def1cf77e1ef84f4373a342e23145be05ec5e226,PMC,Mutational dynamics of the SARS coronavirus in cell culture and human populations isolated in 2003,http://dx.doi.org/10.1186/1471-2334-4-32,PMC517714,15347429,CC BY,"BACKGROUND: The SARS coronavirus is the etiologic agent for the epidemic of the Severe Acute Respiratory Syndrome. The recent emergence of this new pathogen, the careful tracing of its transmission patterns, and the ability to propagate in culture allows the exploration of the mutational dynamics of the SARS-CoV in human populations. METHODS: We sequenced complete SARS-CoV genomes taken from primary human tissues (SIN3408, SIN3725V, SIN3765V), cultured isolates (SIN848, SIN846, SIN842, SIN845, SIN847, SIN849, SIN850, SIN852, SIN3408L), and five consecutive Vero cell passages (SIN2774_P1, SIN2774_P2, SIN2774_P3, SIN2774_P4, SIN2774_P5) arising from SIN2774 isolate. These represented individual patient samples, serial in vitro passages in cell culture, and paired human and cell culture isolates. Employing a refined mutation filtering scheme and constant mutation rate model, the mutation rates were estimated and the possible date of emergence was calculated. Phylogenetic analysis was used to uncover molecular relationships between the isolates. RESULTS: Close examination of whole genome sequence of 54 SARS-CoV isolates identified before 14(th )October 2003, including 22 from patients in Singapore, revealed the mutations engendered during human-to-Vero and Vero-to-human transmission as well as in multiple Vero cell passages in order to refine our analysis of human-to-human transmission. Though co-infection by different quasipecies in individual tissue samples is observed, the in vitro mutation rate of the SARS-CoV in Vero cell passage is negligible. The in vivo mutation rate, however, is consistent with estimates of other RNA viruses at approximately 5.7 × 10(-6 )nucleotide substitutions per site per day (0.17 mutations per genome per day), or two mutations per human passage (adjusted R-square = 0.4014). Using the immediate Hotel M contact isolates as roots, we observed that the SARS epidemic has generated four major genetic groups that are geographically associated: two Singapore isolates, one Taiwan isolate, and one North China isolate which appears most closely related to the putative SARS-CoV isolated from a palm civet. Non-synonymous mutations are centered in non-essential ORFs especially in structural and antigenic genes such as the S and M proteins, but these mutations did not distinguish the geographical groupings. However, no non-synonymous mutations were found in the 3CLpro and the polymerase genes. CONCLUSIONS: Our results show that the SARS-CoV is well adapted to growth in culture and did not appear to undergo specific selection in human populations. We further assessed that the putative origin of the SARS epidemic was in late October 2002 which is consistent with a recent estimate using cases from China. The greater sequence divergence in the structural and antigenic proteins and consistent deletions in the 3' – most portion of the viral genome suggest that certain selection pressures are interacting with the functional nature of these validated and putative ORFs.",2004 Sep 6,"['Vega, Vinsensius B', 'Ruan, Yijun', 'Liu, Jianjun', 'Lee, Wah Heng', 'Wei, Chia Lin', 'Se-Thoe, Su Yun', 'Tang, Kin Fai', 'Zhang, Tao', 'Kolatkar, Prasanna R', 'Ooi, Eng Eong', 'Ling, Ai Ee', 'Stanton, Lawrence W', 'Long, Philip M', 'Liu, Edison T']",BMC Infect Dis,,,True
cd1d0cb4b82d5479e2aa72ec3d3cde6aae4a4eaf,PMC,Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay,http://dx.doi.org/10.1128/mSphere.00334-16,PMC5177731,28028546,CC BY,"Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.",2016 Dec 21,"['Rigatti, Lora H.', 'Toptan, Tuna', 'Newsome, Joseph T.', 'Moore, Patrick S.', 'Chang, Yuan']",mSphere,,,True
c1463986f2df7695fca3d8e5ef31faea5751b062,PMC,Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay,http://dx.doi.org/10.1128/mSphere.00334-16,PMC5177731,28028546,CC BY,"Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.",2016 Dec 21,"['Rigatti, Lora H.', 'Toptan, Tuna', 'Newsome, Joseph T.', 'Moore, Patrick S.', 'Chang, Yuan']",mSphere,,,False
02fe25fbb0d56b029e8430d15c6477cc8a60cfbf,PMC,Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay,http://dx.doi.org/10.1128/mSphere.00334-16,PMC5177731,28028546,CC BY,"Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.",2016 Dec 21,"['Rigatti, Lora H.', 'Toptan, Tuna', 'Newsome, Joseph T.', 'Moore, Patrick S.', 'Chang, Yuan']",mSphere,,,False
f12c46cf0ce9bbb550db15686c35cbaf93675f9b,PMC,Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay,http://dx.doi.org/10.1128/mSphere.00334-16,PMC5177731,28028546,CC BY,"Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.",2016 Dec 21,"['Rigatti, Lora H.', 'Toptan, Tuna', 'Newsome, Joseph T.', 'Moore, Patrick S.', 'Chang, Yuan']",mSphere,,,False
41de90ca9d6f6a18e6f89d479e3fd8160997a14d,PMC,Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay,http://dx.doi.org/10.1128/mSphere.00334-16,PMC5177731,28028546,CC BY,"Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.",2016 Dec 21,"['Rigatti, Lora H.', 'Toptan, Tuna', 'Newsome, Joseph T.', 'Moore, Patrick S.', 'Chang, Yuan']",mSphere,,,False
107ccec688fb89790d2e34288f7eeba5ef7711aa,PMC,Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay,http://dx.doi.org/10.1128/mSphere.00334-16,PMC5177731,28028546,CC BY,"Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.",2016 Dec 21,"['Rigatti, Lora H.', 'Toptan, Tuna', 'Newsome, Joseph T.', 'Moore, Patrick S.', 'Chang, Yuan']",mSphere,,,False
6d5428a39bf922573570819e724cd7db07fb79f9,PMC,Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay,http://dx.doi.org/10.1128/mSphere.00334-16,PMC5177731,28028546,CC BY,"Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.",2016 Dec 21,"['Rigatti, Lora H.', 'Toptan, Tuna', 'Newsome, Joseph T.', 'Moore, Patrick S.', 'Chang, Yuan']",mSphere,,,False
c52372f0295a7cd5d07b677dee5360d634d6a394,PMC,The interdependent complexity of disaster and Middle East Respiratory Syndrome,http://dx.doi.org/10.4178/epih.e2016053,PMC5177800,27899024,CC BY,,2016 Nov 28,"Lee, Wonjae",Epidemiol Health,,,False
cf88f594fcb494d7147df36623227c897c385645,PMC,The interdependent complexity of disaster and Middle East Respiratory Syndrome,http://dx.doi.org/10.4178/epih.e2016053,PMC5177800,27899024,CC BY,,2016 Nov 28,"Lee, Wonjae",Epidemiol Health,,,False
abfbd54f647f1110848e0d711303e92b55f15ab2,PMC,Psychological trauma of Middle East Respiratory Syndrome victims and bereaved families,http://dx.doi.org/10.4178/epih.e2016054,PMC5177804,27919121,CC BY,,2016 Dec 2,"Sim, Minyoung",Epidemiol Health,,,False
f906ff51f4ba98a52133c1cfea59ee9420e3b0fc,PMC,Psychological trauma of Middle East Respiratory Syndrome victims and bereaved families,http://dx.doi.org/10.4178/epih.e2016054,PMC5177804,27919121,CC BY,,2016 Dec 2,"Sim, Minyoung",Epidemiol Health,,,False
344057fa7bef9619bf39e1d681ab054048949e75,PMC,Mental health status of people isolated due to Middle East Respiratory Syndrome,http://dx.doi.org/10.4178/epih.e2016048,PMC5177805,28196409,CC BY,"OBJECTIVES: Isolation due to the management of infectious diseases is thought to affect mental health, but the effects are still unknown. We examined the prevalence of anxiety symptoms and anger in persons isolated during the Middle East Respiratory Syndrome (MERS) epidemic both at isolation period and at four to six months after release from isolation. We also determined risk factors associated with these symptoms at four to six months. METHODS: Of 14,992 individuals isolated for 2-week due to having contact with MERS patients in 2015, when MERS was introduced to Korea, 1,692 individuals were included in this study. Anxiety symptoms were evaluated with the Generalized Anxiety Disorder 7-item scale and anger was assessed with the State-Trait Anger Expression Inventory at four to six months after release from isolation for MERS. RESULTS: Of 1,692 who came in contact with MERS patients, 1,656 were not diagnosed with MERS. Among 1,656, anxiety symptoms showed 7.6% (95% confidence interval [CI], 6.3 to 8.9%) and feelings of anger were present in 16.6% (95% CI, 14.8 to 18.4%) during the isolation period. At four to six months after release from isolation, anxiety symptoms were observed in 3.0% (95%CI, 2.2 to 3.9%). Feelings of anger were present in 6.4% (95% CI, 5.2 to 7.6%). Risk factors for experiencing anxiety symptoms and anger at four to six months after release included symptoms related to MERS during isolation, inadequate supplies (food, clothes, accommodation), social networking activities (email, text, Internet), history of psychiatric illnesses, and financial loss. CONCLUSIONS: Mental health problems at four to six month after release from isolation might be prevented by providing mental health support to individuals with vulnerable mental health, and providing accurate information as well as appropriate supplies, including food, clothes, and accommodation.",2016 Nov 5,"['Jeong, Hyunsuk', 'Yim, Hyeon Woo', 'Song, Yeong-Jun', 'Ki, Moran', 'Min, Jung-Ah', 'Cho, Juhee', 'Chae, Jeong-Ho']",Epidemiol Health,,,True
be0098a38881944590f4d51d6e29bf4e616267e9,PMC,Mental health status of people isolated due to Middle East Respiratory Syndrome,http://dx.doi.org/10.4178/epih.e2016048,PMC5177805,28196409,CC BY,"OBJECTIVES: Isolation due to the management of infectious diseases is thought to affect mental health, but the effects are still unknown. We examined the prevalence of anxiety symptoms and anger in persons isolated during the Middle East Respiratory Syndrome (MERS) epidemic both at isolation period and at four to six months after release from isolation. We also determined risk factors associated with these symptoms at four to six months. METHODS: Of 14,992 individuals isolated for 2-week due to having contact with MERS patients in 2015, when MERS was introduced to Korea, 1,692 individuals were included in this study. Anxiety symptoms were evaluated with the Generalized Anxiety Disorder 7-item scale and anger was assessed with the State-Trait Anger Expression Inventory at four to six months after release from isolation for MERS. RESULTS: Of 1,692 who came in contact with MERS patients, 1,656 were not diagnosed with MERS. Among 1,656, anxiety symptoms showed 7.6% (95% confidence interval [CI], 6.3 to 8.9%) and feelings of anger were present in 16.6% (95% CI, 14.8 to 18.4%) during the isolation period. At four to six months after release from isolation, anxiety symptoms were observed in 3.0% (95%CI, 2.2 to 3.9%). Feelings of anger were present in 6.4% (95% CI, 5.2 to 7.6%). Risk factors for experiencing anxiety symptoms and anger at four to six months after release included symptoms related to MERS during isolation, inadequate supplies (food, clothes, accommodation), social networking activities (email, text, Internet), history of psychiatric illnesses, and financial loss. CONCLUSIONS: Mental health problems at four to six month after release from isolation might be prevented by providing mental health support to individuals with vulnerable mental health, and providing accurate information as well as appropriate supplies, including food, clothes, and accommodation.",2016 Nov 5,"['Jeong, Hyunsuk', 'Yim, Hyeon Woo', 'Song, Yeong-Jun', 'Ki, Moran', 'Min, Jung-Ah', 'Cho, Juhee', 'Chae, Jeong-Ho']",Epidemiol Health,,,True
d49cee8c7a1dcbaf01f8b3126ba8bc7b9ead7a5a,PMC,Effective risk governance requires risk communication experts,http://dx.doi.org/10.4178/epih.e2016055,PMC5177806,27919122,CC BY,,2016 Dec 2,"Paek, Hye-Jin",Epidemiol Health,,,True
6f207ad75048739d35ad460224c267150c18ad54,PMC,Effective risk governance requires risk communication experts,http://dx.doi.org/10.4178/epih.e2016055,PMC5177806,27919122,CC BY,,2016 Dec 2,"Paek, Hye-Jin",Epidemiol Health,,,False
77ced9eec3817dd81f3b38b19086ba07b271208f,PMC,Cross-protective efficacy of dendritic cells targeting conserved influenza virus antigen expressed by Lactobacillus plantarum,http://dx.doi.org/10.1038/srep39665,PMC5177883,28004787,CC BY,"Avian influenza virus (AIV) can infect birds and mammals, including humans, and are thus a serious threat to public health. Vaccination is vital for controlling AIV circulation. In this study, we generated a recombinant lactobacillus expressing the NP-M1-DCpep of H9N2 avian influenza virus and evaluated the activation effect of NC8-pSIP409-NP-M1-DCpep on dendritic cells (DCs) in a mouse model. The specific mucosal antibody responses and B and T cell responses in lymphoid tissues were also characterized. Importantly, we confirmed that specific CD8 T cells presented in vitro and antigen-specific cytotoxicity (activated the expression of CD107a) and in vivo antigen-specific cytotoxicity after vaccination. The adoptive transfer of NC8-pSIP409-NP-M1-DCpep-primed CD8(+) T cells into NOD-SCID mice resulted in effective protection against mouse-adapted AIV infection. In addition, we observed protection in immunized mice challenged with mouse-adapted H9N2 AIV and H1N1 influenza virus, as evidenced by reductions in the lung virus titers, improvements in lung pathology, and weight loss and complete survival. Our data are promising for the generation of effective, non-traditional influenza vaccines against AIVs.",2016 Dec 22,"['Yang, Wen-Tao', 'Shi, Shao-Hua', 'Yang, Gui-Lian', 'Jiang, Yan-Long', 'Zhao, Liang', 'Li, Yu', 'Wang, Chun-Feng']",Sci Rep,,,True
4fcf6dedbf15427b8516654a5a24fbce54fb4b2a,PMC,Cross-protective efficacy of dendritic cells targeting conserved influenza virus antigen expressed by Lactobacillus plantarum,http://dx.doi.org/10.1038/srep39665,PMC5177883,28004787,CC BY,"Avian influenza virus (AIV) can infect birds and mammals, including humans, and are thus a serious threat to public health. Vaccination is vital for controlling AIV circulation. In this study, we generated a recombinant lactobacillus expressing the NP-M1-DCpep of H9N2 avian influenza virus and evaluated the activation effect of NC8-pSIP409-NP-M1-DCpep on dendritic cells (DCs) in a mouse model. The specific mucosal antibody responses and B and T cell responses in lymphoid tissues were also characterized. Importantly, we confirmed that specific CD8 T cells presented in vitro and antigen-specific cytotoxicity (activated the expression of CD107a) and in vivo antigen-specific cytotoxicity after vaccination. The adoptive transfer of NC8-pSIP409-NP-M1-DCpep-primed CD8(+) T cells into NOD-SCID mice resulted in effective protection against mouse-adapted AIV infection. In addition, we observed protection in immunized mice challenged with mouse-adapted H9N2 AIV and H1N1 influenza virus, as evidenced by reductions in the lung virus titers, improvements in lung pathology, and weight loss and complete survival. Our data are promising for the generation of effective, non-traditional influenza vaccines against AIVs.",2016 Dec 22,"['Yang, Wen-Tao', 'Shi, Shao-Hua', 'Yang, Gui-Lian', 'Jiang, Yan-Long', 'Zhao, Liang', 'Li, Yu', 'Wang, Chun-Feng']",Sci Rep,,,True
03a158fb5fcbfccd841b4a9638e840a0302b9459,PMC,The DE and FG loops of the HPV major capsid protein contribute to the epitopes of vaccine-induced cross-neutralising antibodies,http://dx.doi.org/10.1038/srep39730,PMC5177933,28004837,CC BY,"The human papillomavirus (HPV) vaccines consist of major capsid protein (L1) virus-like particles (VLP) and are highly efficacious against the development of cervical cancer precursors attributable to oncogenic genotypes, HPV16 and HPV18. A degree of vaccine-induced cross-protection has also been demonstrated against genetically-related genotypes in the Alpha-7 (HPV18-like) and Alpha-9 (HPV16-like) species groups which is coincident with the detection of L1 cross-neutralising antibodies. In this study the L1 domains recognised by inter-genotype cross-neutralising antibodies were delineated. L1 crystallographic homology models predicted a degree of structural diversity between the L1 loops of HPV16 and the non-vaccine Alpha-9 genotypes. These structural predictions informed the design of chimeric pseudovirions with inter-genotype loop swaps which demonstrated that the L1 domains recognised by inter-genotype cross-neutralising antibodies comprise residues within the DE loop and the late region of the FG loop. These data contribute to our understanding of the L1 domains recognised by vaccine-induced cross-neutralising antibodies. Such specificities may play a critical role in vaccine-induced cross-protection.",2016 Dec 22,"['Bissett, Sara L.', 'Godi, Anna', 'Beddows, Simon']",Sci Rep,,,True
02843e9be924677d6541e0221a26501ce2111aaa,PMC,The differentiated airway epithelium infected by influenza viruses maintains the barrier function despite a dramatic loss of ciliated cells,http://dx.doi.org/10.1038/srep39668,PMC5177954,28004801,CC BY,"Virus-host interactions in the respiratory epithelium during long term influenza virus infection are not well characterized. Therefore, we developed an air-liquid interface culture system for differentiated porcine respiratory epithelial cells to study the effect of virus-induced cellular damage. In our well-differentiated cells, α2,6-linked sialic acid is predominantly expressed on the apical surface and the basal cells mainly express α2,3-linked sialic acid. During the whole infection period, release of infectious virus was maintained at a high titre for more than seven days. The infected epithelial cells were subject to apoptosis resulting in the loss of ciliated cells together with a thinner thickness. Nevertheless, the airway epithelium maintained trans-epithelial electrical resistance and retained its barrier function. The loss of ciliated cells was compensated by the cells which contained the KRT5 basal cell marker but were not yet differentiated into ciliated cells. These specialized cells showed an increase of α2,3-linked sialic acid on the apical surface. In sum, our results help to explain the localized infection of the airway epithelium by influenza viruses. The impairment of mucociliary clearance in the epithelial cells provides an explanation why prior viral infection renders the host more susceptible to secondary co-infection by another pathogen.",2016 Dec 22,"['Wu, Nai-Huei', 'Yang, Wei', 'Beineke, Andreas', 'Dijkman, Ronald', 'Matrosovich, Mikhail', 'Baumgärtner, Wolfgang', 'Thiel, Volker', 'Valentin-Weigand, Peter', 'Meng, Fandan', 'Herrler, Georg']",Sci Rep,,,True
31cfa31a4d8a26ca083257be0e6dce51562d8c6d,PMC,Respiratory Antiviral Immunity and Immunobiotics: Beneficial Effects on Inflammation-Coagulation Interaction during Influenza Virus Infection,http://dx.doi.org/10.3389/fimmu.2016.00633,PMC5179578,28066442,CC BY,"Influenza virus (IFV) is a major respiratory pathogen of global importance, and the cause of a high degree of morbidity and mortality, especially in high-risk populations such as infants, elderly, and immunocompromised hosts. Given its high capacity to change antigenically, acquired immunity is often not effective to limit IFV infection and therefore vaccination must be constantly redesigned to achieve effective protection. Improvement of respiratory and systemic innate immune mechanisms has been proposed to reduce the incidence and severity of IFV disease. In the last decade, several research works have demonstrated that microbes with the capacity to modulate the mucosal immune system (immunobiotics) are a potential alternative to beneficially modulate the outcome of IFV infection. This review provides an update of the current status on the modulation of respiratory immunity by orally and nasally administered immunobiotics, and their beneficial impact on IFV clearance and inflammatory-mediated lung tissue damage. In particular, we describe the research of our group that investigated the influence of immunobiotics on inflammation–coagulation interactions during IFV infection. Studies have clearly demonstrated that hostile inflammation is accompanied by dysfunctional coagulation in respiratory IFV disease, and our investigations have proved that some immunobiotic strains are able to reduce viral disease severity through their capacity to modulate the immune-coagulative responses in the respiratory tract.",2016 Dec 23,"['Zelaya, Hortensia', 'Alvarez, Susana', 'Kitazawa, Haruki', 'Villena, Julio']",Front Immunol,,,True
37d6ce7eabf4b6177b9462771494c7c2fc36e5ee,PMC,Integrated biological–behavioural surveillance in pandemic-threat warning systems,http://dx.doi.org/10.2471/BLT.16.175984,PMC5180348,28053365,CC BY,"Economically and politically disruptive disease outbreaks are a hallmark of the 21st century. Although pandemics are driven by human behaviours, current surveillance systems for identifying pandemic threats are largely reliant on the monitoring of disease outcomes in clinical settings. Standardized integrated biological–behavioural surveillance could, and should, be used in community settings to complement such clinical monitoring. The usefulness of such an approach has already been demonstrated in studies on human immunodeficiency virus, where integrated surveillance contributed to a biologically based and quantifiable understanding of the behavioural risk factors associated with the transmission dynamics of the virus. When designed according to Strengthening the Reporting of Observational Studies in Epidemiology criteria, integrated surveillance requires that both behavioural risk factors – i.e. exposure variables – and disease-indicator outcome variables be measured in behavioural surveys. In the field of pandemic threats, biological outcome data could address the weaknesses of self-reported data collected in behavioural surveys. Data from serosurveys of viruses with pandemic potential, collected under non-outbreak conditions, indicate that serosurveillance could be used to predict future outbreaks. When conducted together, behavioural surveys and serosurveys could warn of future pandemics, potentially before the disease appears in clinical settings. Traditional disease-outcome surveillance must be frequent and ongoing to remain useful but behavioural surveillance remains informative even if conducted much less often, since behaviour change occurs slowly over time. Only through knowledge of specific behavioural risk factors can interventions and policies that can prevent the next pandemic be developed.",2017 Jan 1,"['Miller, Maureen', 'Hagan, Emily']",Bull World Health Organ,,,True
90b065409490de2813ab71b65ca8b401ec55b356,PMC,Avian H11 influenza virus isolated from domestic poultry in a Colombian live animal market,http://dx.doi.org/10.1038/emi.2016.121,PMC5180366,27924808,CC BY,"Live animal markets (LAMs) are an essential source of food and trade in Latin American countries; however, they can also serve as ‘hotbeds' for the emergence and potential spillover of avian influenza viruses (AIV). Despite extensive knowledge of AIV in Asian LAMs, little is known about the prevalence South American LAMs. To fill this gap in knowledge, active surveillance was carried out at the major LAM in Medellin, Colombia between February and September 2015. During this period, overall prevalence in the market was 2.67% and a North American origin H11N2 AIV most similar to a virus isolated from Chilean shorebirds asymptomatically spread through multiple bird species in the market resulting in 17.0% positivity at peak of infection. Phenotypically, the H11 viruses displayed no known molecular markers associated with increased virulence in birds or mammals, had α2,3-sialic acid binding preference, and caused minimal replication in vitro and little morbidity in vivo. However, the Colombian H11N2 virus replicated and transmitted effectively in chickens explaining the spread throughout the market. Genetic similarity to H11 viruses isolated from North and South American shorebirds suggest that the LAM occurrence may have resulted from a wild bird to domestic poultry spillover event. The ability to spread in domestic poultry as well as potential for human infection by H11 viruses highlight the need for enhanced AIV surveillance in South America in both avian species and humans.",2016 Dec 7,"['Jiménez-Bluhm, Pedro', 'Karlsson, Erik A', 'Ciuoderis, Karl A', 'Cortez, Valerie', 'Marvin, Shauna A', 'Hamilton-West, Christopher', 'Schultz-Cherry, Stacey', 'Osorio, Jorge E']",Emerg Microbes Infect,,,True
18176d1030fff6410b83e0df1591b3617fc739cb,PMC,A camel-derived MERS-CoV with a variant spike protein cleavage site and distinct fusion activation properties,http://dx.doi.org/10.1038/emi.2016.125,PMC5180369,27999426,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) continues to circulate in both humans and camels, and the origin and evolution of the virus remain unclear. Here we characterize the spike protein of a camel-derived MERS-CoV (NRCE-HKU205) identified in 2013, early in the MERS outbreak. NRCE-HKU205 spike protein has a variant cleavage motif with regard to the S2′ fusion activation site—notably, a novel substitution of isoleucine for the otherwise invariant serine at the critical P1′ cleavage site position. The substitutions resulted in a loss of furin-mediated cleavage, as shown by fluorogenic peptide cleavage and western blot assays. Cell–cell fusion and pseudotyped virus infectivity assays demonstrated that the S2′ substitutions decreased spike-mediated fusion and viral entry. However, cathepsin and trypsin-like protease activation were retained, albeit with much reduced efficiency compared with the prototypical EMC/2012 human strain. We show that NRCE-HKU205 has more limited fusion activation properties possibly resulting in more restricted viral tropism and may represent an intermediate in the complex pattern of MERS-CoV ecology and evolution.",2016 Dec 21,"['Millet, Jean Kaoru', 'Goldstein, Monty E', 'Labitt, Rachael N', 'Hsu, Hung-Lun', 'Daniel, Susan', 'Whittaker, Gary R']",Emerg Microbes Infect,,,True
3fcc0c9ff97448fd834d65f22598be89ee20c4a0,PMC,A camel-derived MERS-CoV with a variant spike protein cleavage site and distinct fusion activation properties,http://dx.doi.org/10.1038/emi.2016.125,PMC5180369,27999426,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) continues to circulate in both humans and camels, and the origin and evolution of the virus remain unclear. Here we characterize the spike protein of a camel-derived MERS-CoV (NRCE-HKU205) identified in 2013, early in the MERS outbreak. NRCE-HKU205 spike protein has a variant cleavage motif with regard to the S2′ fusion activation site—notably, a novel substitution of isoleucine for the otherwise invariant serine at the critical P1′ cleavage site position. The substitutions resulted in a loss of furin-mediated cleavage, as shown by fluorogenic peptide cleavage and western blot assays. Cell–cell fusion and pseudotyped virus infectivity assays demonstrated that the S2′ substitutions decreased spike-mediated fusion and viral entry. However, cathepsin and trypsin-like protease activation were retained, albeit with much reduced efficiency compared with the prototypical EMC/2012 human strain. We show that NRCE-HKU205 has more limited fusion activation properties possibly resulting in more restricted viral tropism and may represent an intermediate in the complex pattern of MERS-CoV ecology and evolution.",2016 Dec 21,"['Millet, Jean Kaoru', 'Goldstein, Monty E', 'Labitt, Rachael N', 'Hsu, Hung-Lun', 'Daniel, Susan', 'Whittaker, Gary R']",Emerg Microbes Infect,,,False
f8de6043ca1a372d6ea60880034cfb6abbc4b147,PMC,Polyphyletic origin of MERS coronaviruses and isolation of a novel clade A strain from dromedary camels in the United Arab Emirates,http://dx.doi.org/10.1038/emi.2016.129,PMC5180373,27999424,CC BY,"Little is known regarding the molecular epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) circulating in dromedaries outside Saudi Arabia. To address this knowledge gap, we sequenced 10 complete genomes of MERS-CoVs isolated from 2 live and 8 dead dromedaries from different regions in the United Arab Emirates (UAE). Phylogenetic analysis revealed one novel clade A strain, the first detected in the UAE, and nine clade B strains. Strain D998/15 had a distinct phylogenetic position within clade A, being more closely related to the dromedary isolate NRCE-HKU205 from Egypt than to the human isolates EMC/2012 and Jordan-N3/2012. A comparison of predicted protein sequences also demonstrated the existence of two clade A lineages with unique amino acid substitutions, A1 (EMC/2012 and Jordan-N3/2012) and A2 (D998/15 and NRCE-HKU205), circulating in humans and camels, respectively. The nine clade B isolates belong to three distinct lineages: B1, B3 and B5. Two B3 strains, D1271/15 and D1189.1/15, showed evidence of recombination between lineages B4 and B5 in ORF1ab. Molecular clock analysis dated the time of the most recent common ancestor (tMRCA) of clade A to March 2011 and that of clade B to November 2011. Our data support a polyphyletic origin of MERS-CoV in dromedaries and the co-circulation of diverse MERS-CoVs including recombinant strains in the UAE.",2016 Dec 21,"['Lau, Susanna K P', 'Wernery, Renate', 'Wong, Emily Y M', 'Joseph, Sunitha', 'Tsang, Alan K L', 'Patteril, Nissy Annie Georgy', 'Elizabeth, Shyna K', 'Chan, Kwok-Hung', 'Muhammed, Rubeena', 'Kinne, Jöerg', 'Yuen, Kwok-Yung', 'Wernery, Ulrich', 'Woo, Patrick C Y']",Emerg Microbes Infect,,,True
cd3eeb911617dd22ee6f0d1843e19ba1d255e133,PMC,Loop-Mediated Isothermal Amplification (LAMP): Emergence As an Alternative Technology for Herbal Medicine Identification,http://dx.doi.org/10.3389/fpls.2016.01956,PMC5183589,28082999,CC BY,"Correct identification of medicinal plant ingredients is essential for their safe use and for the regulation of herbal drug supply chain. Loop-mediated isothermal amplification (LAMP) is a recently developed approach to identify herbal medicine species. This novel molecular biology technique enables timely and accurate testing, especially in settings where infrastructures to support polymerase chain reaction facilities are lacking. Studies that used this method have altered our view on the extent and complexity of herbal medicine identification. In this review, we give an introduction into LAMP analysis, covers the basic principles and important aspects in the development of LAMP analysis method. Then we presented a critical review of the application of LAMP-based methods in detecting and identifying raw medicinal plant materials and their processed products. We also provide a practical standard operating procedure (SOP) for the utilization of the LAMP protocol in herbal authentication, and consider the prospects of LAMP technology in the future developments of herbal medicine identification and the challenges associated with its application.",2016 Dec 26,"['Li, Jing-jian', 'Xiong, Chao', 'Liu, Yue', 'Liang, Jun-song', 'Zhou, Xing-wen']",Front Plant Sci,,,True
45d2d838cb3d5ae2dabd7bb7c82329b398d1c65f,PMC,A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection,http://dx.doi.org/10.1186/1471-2334-4-34,PMC518965,15357874,CC BY,"BACKGROUND: The molecular basis of severe acute respiratory syndrome (SARS) coronavirus (CoV) induced pathology is still largely unclear. Many SARS patients suffer respiratory distress brought on by interstitial infiltration and frequently show peripheral blood lymphopenia and occasional leucopenia. One possible cause of this could be interstitial inflammation, following a localized host response. In this study, we therefore examine the immune response of SARS-CoV in human peripheral blood mononuclear cells (PBMCs) over the first 24 hours. METHODS: PBMCs from normal healthy donors were inoculated in vitro with SARS-CoV and the viral replication kinetics was studied by real-time quantitative assays. SARS-CoV specific gene expression changes were examined by high-density oligonucleotide array analysis. RESULTS: We observed that SARS-CoV was capable of infecting and replicating in PBMCs and the kinetics of viral replication was variable among the donors. SARS-CoV antibody binding assays indicated that SARS specific antibodies inhibited SARS-CoV viral replication. Array data showed monocyte-macrophage cell activation, coagulation pathway upregulation and cytokine production together with lung trafficking chemokines such as IL8 and IL17, possibly activated through the TLR9 signaling pathway; that mimicked clinical features of the disease. CONCLUSIONS: The identification of human blood mononuclear cells as a direct target of SARS-CoV in the model system described here provides a new insight into disease pathology and a tool for investigating the host response and mechanisms of pathogenesis.",2004 Sep 9,"['Ng, Lisa FP', 'Hibberd, Martin L', 'Ooi, Eng-Eong', 'Tang, Kin-Fai', 'Neo, Soek-Ying', 'Tan, Jenny', 'Krishna Murthy, Karuturi R', 'Vega, Vinsensius B', 'Chia, Jer-Ming', 'Liu, Edison T', 'Ren, Ee-Chee']",BMC Infect Dis,,,True
1b57217c350c53ef4e96049f9f35bf07b8089976,PMC,A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection,http://dx.doi.org/10.1186/1471-2334-4-34,PMC518965,15357874,CC BY,"BACKGROUND: The molecular basis of severe acute respiratory syndrome (SARS) coronavirus (CoV) induced pathology is still largely unclear. Many SARS patients suffer respiratory distress brought on by interstitial infiltration and frequently show peripheral blood lymphopenia and occasional leucopenia. One possible cause of this could be interstitial inflammation, following a localized host response. In this study, we therefore examine the immune response of SARS-CoV in human peripheral blood mononuclear cells (PBMCs) over the first 24 hours. METHODS: PBMCs from normal healthy donors were inoculated in vitro with SARS-CoV and the viral replication kinetics was studied by real-time quantitative assays. SARS-CoV specific gene expression changes were examined by high-density oligonucleotide array analysis. RESULTS: We observed that SARS-CoV was capable of infecting and replicating in PBMCs and the kinetics of viral replication was variable among the donors. SARS-CoV antibody binding assays indicated that SARS specific antibodies inhibited SARS-CoV viral replication. Array data showed monocyte-macrophage cell activation, coagulation pathway upregulation and cytokine production together with lung trafficking chemokines such as IL8 and IL17, possibly activated through the TLR9 signaling pathway; that mimicked clinical features of the disease. CONCLUSIONS: The identification of human blood mononuclear cells as a direct target of SARS-CoV in the model system described here provides a new insight into disease pathology and a tool for investigating the host response and mechanisms of pathogenesis.",2004 Sep 9,"['Ng, Lisa FP', 'Hibberd, Martin L', 'Ooi, Eng-Eong', 'Tang, Kin-Fai', 'Neo, Soek-Ying', 'Tan, Jenny', 'Krishna Murthy, Karuturi R', 'Vega, Vinsensius B', 'Chia, Jer-Ming', 'Liu, Edison T', 'Ren, Ee-Chee']",BMC Infect Dis,,,False
5bb2fe58be63844d5b13a6b0cacd3ec2c80d3cb3,PMC,Replicon RNA Viral Vectors as Vaccines,http://dx.doi.org/10.3390/vaccines4040039,PMC5192359,27827980,CC BY,"Single-stranded RNA viruses of both positive and negative polarity have been used as vectors for vaccine development. In this context, alphaviruses, flaviviruses, measles virus and rhabdoviruses have been engineered for expression of surface protein genes and antigens. Administration of replicon RNA vectors has resulted in strong immune responses and generation of neutralizing antibodies in various animal models. Immunization of mice, chicken, pigs and primates with virus-like particles, naked RNA or layered DNA/RNA plasmids has provided protection against challenges with lethal doses of infectious agents and administered tumor cells. Both prophylactic and therapeutic efficacy has been achieved in cancer immunotherapy. Moreover, recombinant particles and replicon RNAs have been encapsulated by liposomes to improve delivery and targeting. Replicon RNA vectors have also been subjected to clinical trials. Overall, immunization with self-replicating RNA viruses provides high transient expression levels of antigens resulting in generation of neutralizing antibody responses and protection against lethal challenges under safe conditions.",2016 Nov 7,"Lundstrom, Kenneth",Vaccines (Basel),,,True
fc524fbd93be3db421c75c589e2299524a75fa26,PMC,"Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models",http://dx.doi.org/10.3390/v8120322,PMC5192383,27916837,CC BY,"Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is widely used as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in Vero cells, human brain microvascular endothelial cells, human neural stem cells, and mouse neurospheres. We demonstrate that chloroquine reduces the number of ZIKV-infected cells in vitro, and inhibits virus production and cell death promoted by ZIKV infection without cytotoxic effects. In addition, chloroquine treatment partially reveres morphological changes induced by ZIKV infection in mouse neurospheres.",2016 Nov 29,"['Delvecchio, Rodrigo', 'Higa, Luiza M.', 'Pezzuto, Paula', 'Valadão, Ana Luiza', 'Garcez, Patrícia P.', 'Monteiro, Fábio L.', 'Loiola, Erick C.', 'Dias, André A.', 'Silva, Fábio J. M.', 'Aliota, Matthew T.', 'Caine, Elizabeth A.', 'Osorio, Jorge E.', 'Bellio, Maria', 'O’Connor, David H.', 'Rehen, Stevens', 'de Aguiar, Renato Santana', 'Savarino, Andrea', 'Campanati, Loraine', 'Tanuri, Amilcar']",Viruses,,,True
044b6504465e3d1b00fcc328c6731bcd034b1691,PMC,Comparative Proteome Analysis of Porcine Jejunum Tissues in Response to a Virulent Strain of Porcine Epidemic Diarrhea Virus and Its Attenuated Strain,http://dx.doi.org/10.3390/v8120323,PMC5192384,27916855,CC BY,"Porcine epidemic diarrhea virus (PEDV), a predominant cause of acute enteric infection, leads to severe dehydrating diarrhea and mortality in piglets all over the world. A virulent PEDV YN13 strain, isolated in our laboratory, was attenuated to yield an attenuated PEDV strain YN144. To better understand the pathogenesis mechanism and the virus-host interaction during infection with both PEDV YN13 and YN144 strains, a comparative proteomic analysis was carried out to investigate the proteomic changes produced in the primary target organ, using isobaric tags for relative and absolute quantitation (iTRAQ) labeling, followed by liquid chromatography tandem-mass spectrometry (LC-MS/MS). A total of 269 and 301 differently expressed proteins (DEPs) were identified in the jejunum tissues of the piglets inoculated with YN13 and YN144, respectively. Bioinformatics analysis revealed that these proteins were involved in stress responses, signal transduction, and the immune system. All of these involved interferon-stimulated genes (ISGs) which were up-regulated in jejunums by both of the PEDV-infected groups. Based on the comparative analysis, we proposed that different changes induced by YN13 and YN144 in heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), eukaryotic initiation factor 4G1 (eIF4G1), and some members in the heat shock protein (HSP) family, may be responsible for differences in their pathogenicity.",2016 Nov 29,"['Li, Zhonghua', 'Chen, Fangzhou', 'Ye, Shiyi', 'Guo, Xiaozhen', 'Muhanmmad Memon, Atta', 'Wu, Meizhou', 'He, Qigai']",Viruses,,,True
2ace5853970e68deefd9800fdd135a266237884a,PMC,Characterization of an Immunodominant Epitope in the Endodomain of the Coronavirus Membrane Protein,http://dx.doi.org/10.3390/v8120327,PMC5192388,27973413,CC BY,"The coronavirus membrane (M) protein acts as a dominant immunogen and is a major player in virus assembly. In this study, we prepared two monoclonal antibodies (mAbs; 1C3 and 4C7) directed against the transmissible gastroenteritis virus (TGEV) M protein. The 1C3 and 4C7 mAbs both reacted with the native TGEV M protein in western blotting and immunofluorescence (IFA) assays. Two linear epitopes, 243YSTEART249 (1C3) and 243YSTEARTDNLSEQEKLLHMV262 (4C7), were identified in the endodomain of the TGEV M protein. The 1C3 mAb can be used for the detection of the TGEV M protein in different assays. An IFA method for the detection of TGEV M protein was optimized using mAb 1C3. Furthermore, the ability of the epitope identified in this study to stimulate antibody production was also evaluated. An immunodominant epitope in the TGEV membrane protein endodomain was identified. The results of this study have implications for further research on TGEV replication.",2016 Dec 10,"['Dong, Hui', 'Zhang, Xin', 'Shi, Hongyan', 'Chen, Jianfei', 'Shi, Da', 'Zhu, Yunnuan', 'Feng, Li']",Viruses,,,True
2a246ea75b64133cf7210fa8971a6d43917da132,PMC,Pharmacokinetics of the Antiviral Lectin Griffithsin Administered by Different Routes Indicates Multiple Potential Uses,http://dx.doi.org/10.3390/v8120331,PMC5192392,27999325,CC BY,"Griffithsin (GRFT) is a red alga-derived lectin with demonstrated broad spectrum antiviral activity against enveloped viruses, including severe acute respiratory syndrome–Coronavirus (SARS-CoV), Japanese encephalitis virus (JEV), hepatitis C virus (HCV), and herpes simplex virus-2 (HSV-2). However, its pharmacokinetic profile remains largely undefined. Here, Sprague Dawley rats were administered a single dose of GRFT at 10 or 20 mg/kg by intravenous, oral, and subcutaneous routes, respectively, and serum GRFT levels were measured at select time points. In addition, the potential for systemic accumulation after oral dosing was assessed in rats after 10 daily treatments with GRFT (20 or 40 mg/kg). We found that parenterally-administered GRFT in rats displayed a complex elimination profile, which varied according to administration routes. However, GRFT was not orally bioavailable, even after chronic treatment. Nonetheless, active GRFT capable of neutralizing HIV-Env pseudoviruses was detected in rat fecal extracts after chronic oral dosing. These findings support further evaluation of GRFT for pre-exposure prophylaxis against emerging epidemics for which specific therapeutics are not available, including systemic and enteric infections caused by susceptible enveloped viruses. In addition, GRFT should be considered for antiviral therapy and the prevention of rectal transmission of HIV-1 and other susceptible viruses.",2016 Dec 17,"['Barton, Christopher', 'Kouokam, J. Calvin', 'Hurst, Harrell', 'Palmer, Kenneth E.']",Viruses,,,True
9be5f21d6d5bc49f664d559e63c68f6410a39ae4,PMC,Equine Immunoglobulin and Equine Neutralizing F(ab′)(2) Protect Mice from West Nile Virus Infection,http://dx.doi.org/10.3390/v8120332,PMC5192393,27999340,CC BY,"West Nile virus (WNV) is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to prevent WNV disease. In this study, we prepared and evaluated the protective efficacy of immune serum IgG and pepsin-digested F(ab′)(2) fragments from horses immunized with the WNV virus-like particles (VLP) expressing the WNV M and E proteins. Immune equine F(ab′)(2) fragments and immune horse sera efficiently neutralized WNV infection in tissue culture. The passive transfer of equine immune antibodies significantly accelerated the virus clearance in the spleens and brains of WNV infected mice, and reduced mortality. Thus, equine immunoglobulin or equine neutralizing F(ab′)(2) passive immunotherapy is a potential strategy for the prophylactic or therapeutic treatment of patients infected with WNV.",2016 Dec 18,"['Cui, Jiannan', 'Zhao, Yongkun', 'Wang, Hualei', 'Qiu, Boning', 'Cao, Zengguo', 'Li, Qian', 'Zhang, Yanbo', 'Yan, Feihu', 'Jin, Hongli', 'Wang, Tiecheng', 'Sun, Weiyang', 'Feng, Na', 'Gao, Yuwei', 'Sun, Jing', 'Wang, Yanqun', 'Perlman, Stanley', 'Zhao, Jincun', 'Yang, Songtao', 'Xia, Xianzhu']",Viruses,,,True
4564fff695ff930d022c77efecde703856943b7f,PMC,Transspecies Transmission of Gammaretroviruses and the Origin of the Gibbon Ape Leukaemia Virus (GaLV) and the Koala Retrovirus (KoRV),http://dx.doi.org/10.3390/v8120336,PMC5192397,27999419,CC BY,"Transspecies transmission of retroviruses is a frequent event, and the human immunodeficiency virus-1 (HIV-1) is a well-known example. The gibbon ape leukaemia virus (GaLV) and koala retrovirus (KoRV), two gammaretroviruses, are also the result of a transspecies transmission, however from a still unknown host. Related retroviruses have been found in Southeast Asian mice although the sequence similarity was limited. Viruses with a higher sequence homology were isolated from Melomys burtoni, the Australian and Indonesian grassland melomys. However, only the habitats of the koalas and the grassland melomys in Australia are overlapping, indicating that the melomys virus may not be the precursor of the GaLV. Viruses closely related to GaLV/KoRV were also detected in bats. Therefore, given the fact that the habitats of the gibbons in Thailand and the koalas in Australia are far away, and that bats are able to fly over long distances, the hypothesis that retroviruses of bats are the origin of GaLV and KoRV deserves consideration. Analysis of previous transspecies transmissions of retroviruses may help to evaluate the potential of transmission of related retroviruses in the future, e.g., that of porcine endogenous retroviruses (PERVs) during xenotransplantation using pig cells, tissues or organs.",2016 Dec 20,"Denner, Joachim",Viruses,,,True
24c739b85e7c9082d00e9680cf7a99070c427d55,PMC,Resistance of Aerosolized Bacterial Viruses to Four Germicidal Products,http://dx.doi.org/10.1371/journal.pone.0168815,PMC5193356,28030577,CC BY,"Viral diseases can spread through a variety of routes including aerosols. Yet, limited data are available on the efficacy of aerosolized chemicals to reduce viral loads in the air. Bacteriophages (phages) are often used as surrogates for hazardous viruses in aerosol studies because they are inexpensive, easy to handle, and safe for laboratory workers. Moreover, several of these bacterial viruses display physical characteristics similar to pathogenic human and animal viruses, like morphological size, type of nucleic acids, capsid morphology, and the presence of an envelope. In this study, the efficacy of four chemicals was evaluated on four airborne phages at two different relative humidity levels. Non-tailed bacteriophages MS2 (single-stranded RNA), ϕ6 (double-stranded RNA, enveloped), PR772 (double-stranded DNA), and ϕX174 (single-stranded DNA) were first aerosolized in a 55L rotative environmental chamber at 19°C with 25% and 50% relative humidity. Then, hydrogen peroxide, Eugenol (phenylpropene used in commercial perfumes and flavorings), Mist(®) (automobile disinfectant containing Triethylene glycol), and Pledge(®) (multisurface disinfectant containing Isopropanol, n-Alkyl Dimethyl Benzyl Amonium Chlorides, and n-Alkyl Dimethyl Ethylbenzyl Ammonium Chloride) were nebulized with the phages using a separate nebulizer. Aerosols were maintained in suspension during 10 minutes, 1 hour, and 2 hours. Viral aerosols were sampled using an SKC BioSampler and samples were analyzed using qPCR and plaque assays. The resistance levels of the four phages varied depending on the relative humidity (RH) and germicidal products tested. Phage MS2 was the most stable airborne virus under the environmental conditions tested while phage PR772 was the least stable. Pledge(®) and Eugenol reduced the infectivity of all airborne phages tested. At 25% RH, Pledge(®) and Eugenol were more effective at reducing infectivity of RNA phages ϕ6 and MS2. At 50% RH, Pledge(®) was the most effective agent against phage MS2. These findings illustrate that various airborne viruses should be tested to demonstrate the effectiveness of germicidal treatments. This research also provides a set of parameters for testing germicidal products in large-scale settings to reduce the risk of virus transmission.",2016 Dec 28,"['Turgeon, Nathalie', 'Michel, Kevin', 'Ha, Thi-Lan', 'Robine, Enric', 'Moineau, Sylvain', 'Duchaine, Caroline']",PLoS One,,,True
48106886ec5b19e6cc62abf552ff3529f1d8aca3,PMC,The presence of fever in adults with influenza and other viral respiratory infections,http://dx.doi.org/10.1017/S0950268816002181,PMC5197931,27691995,CC BY,"We compared the rates of fever in adult subjects with laboratory-confirmed influenza and other respiratory viruses and examined the factors that predict fever in adults. Symptom data on 158 healthcare workers (HCWs) with a laboratory-confirmed respiratory virus infection were collected using standardized data collection forms from three separate studies. Overall, the rate of fever in confirmed viral respiratory infections in adult HCWs was 23·4% (37/158). Rates varied by virus: human rhinovirus (25·3%, 19/75), influenza A virus (30%, 3/10), coronavirus (28·6%, 2/7), human metapneumovirus (28·6%, 2/7), respiratory syncytial virus (14·3%, 4/28) and parainfluenza virus (8·3%, 1/12). Smoking [relative risk (RR) 4·65, 95% confidence interval (CI) 1·33–16·25] and co-infection with two or more viruses (RR 4·19, 95% CI 1·21–14·52) were significant predictors of fever. Fever is less common in adults with confirmed viral respiratory infections, including influenza, than described in children. More than 75% of adults with a viral respiratory infection do not have fever, which is an important finding for clinical triage of adult patients with respiratory infections. The accepted definition of ‘influenza-like illness’ includes fever and may be insensitive for surveillance when high case-finding is required. A more sensitive case definition could be used to identify adult cases, particularly in event of an emerging viral infection.",2017 Jan 3,"['CHUGHTAI, A. A.', 'WANG, Q.', 'DUNG, T. C.', 'MACINTYRE, C. R.']",Epidemiol Infect,,,True
430213ca4c52874f7082c2a1d1c3117187e41dae,PMC,Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses,http://dx.doi.org/10.3390/ph9040078,PMC5198053,27999271,CC BY,"Appropriate diagnosis is the key factor for treatment of viral diseases. Time is the most important factor in rapidly developing and epidemiologically dangerous diseases, such as influenza, Ebola and SARS. Chronic viral diseases such as HIV-1 or HCV are asymptomatic or oligosymptomatic and the therapeutic success mainly depends on early detection of the infective agent. Over the last years, aptamer technology has been used in a wide range of diagnostic and therapeutic applications and, concretely, several strategies are currently being explored using aptamers against virus proteins. From a diagnostics point of view, aptamers are being designed as a bio-recognition element in diagnostic systems to detect viral proteins either in the blood (serum or plasma) or into infected cells. Another potential use of aptamers is for therapeutics of viral infections, interfering in the interaction between the virus and the host using aptamers targeting host-cell matrix receptors, or attacking the virus intracellularly, targeting proteins implicated in the viral replication cycle. In this paper, we review how aptamers working against viral proteins are discovered, with a focus on recent advances that improve the aptamers’ properties as a real tool for viral infection detection and treatment.",2016 Dec 16,"['González, Víctor M.', 'Martín, M. Elena', 'Fernández, Gerónimo', 'García-Sacristán, Ana']",Pharmaceuticals (Basel),,,True
25707e09aa87bb548138776e263ab037f4e6cda0,PMC,Heme Oxygenase-1-Expressing Dendritic Cells Promote Foxp3(+) Regulatory T Cell Differentiation and Induce Less Severe Airway Inflammation in Murine Models,http://dx.doi.org/10.1371/journal.pone.0168919,PMC5199094,28033400,CC BY,"Dendritic cells (DCs) are critical for instructing immune responses toward inflammatory or anti-inflammatory status. Heme oxygenase-1 (HO-1) is known for its cytoprotective effect against oxidative stress and inflammation, suggesting its immune regulatory role in allergic lung inflammation. HO-1 has been implicated in affecting DC maturation; however, its role in DC-mediated T-cell differentiation is unclear. In this study, we demonstrated that HO-1-expressing bone marrow-derived dendritic cells (BM-DCs) displayed tolerogenic phenotypes, including their resistance to lipopolysaccharide (LPS)-induced maturation, high level expression of IL-10, and low T-cell stimulatory activity. In addition, HO-1-expressing DCs were able to induce antigen-specific Foxp3(+) regulatory T cells (Treg) differentiation in vitro and in vivo. Also, HO-1-expressing DCs modulated the severity of lung inflammatory responses in two murine models of airway inflammation. This study provided evidence supporting the role of HO-1-expressing DCs in tolerance induction and as a potential therapeutic target for allergic asthma as well as other inflammatory diseases.",2016 Dec 29,"['Wong, Tzu-Hsuan', 'Chen, Hung-An', 'Gau, Rung-Jiun', 'Yen, Jeng-Hsien', 'Suen, Jau-Ling']",PLoS One,,,True
0f52f6ec3e15cc1cc45803c3cb81618d5ee82b7a,PMC,"Coherence of Influenza Surveillance Data across Different Sources and Age Groups, Beijing, China, 2008-2015",http://dx.doi.org/10.1371/journal.pone.0169199,PMC5201231,28036373,CC BY,"Influenza is active during the winter and spring in the city of Beijing, which has a typical temperate climate with four clear distinct seasons. The clinical and laboratory surveillance data for influenza have been used to construct critical indicators for influenza activities in the community, and previous studies have reported varying degrees of association between laboratory-confirmed influenza specimens and outpatient consultation rates of influenza-like illness in subtropical cities. However, few studies have reported on this issue for cities in temperate regions, especially in developing countries. Furthermore, the mechanism behind age-specific seasonal epidemics remains unresolved, although it has been widely discussed. We utilized a wavelet analysis method to monitor the coherence of weekly percentage of laboratory-confirmed influenza specimens with the weekly outpatient consultation rates of influenza-like illness in Beijing, China. We first examined the seasonal pattern of laboratory-confirmed cases of influenza A (subtyped into seasonal A(H1N1) and A(H3N2) and pandemic virus A(H1N1) pdm09) and influenza B separately within the period from 2008–2015; then, we detected the coherence of clinical and laboratory surveillance data in this district, specially examining weekly time series of age-specific epidemics of influenza-like illnesses in the whole study period for three age categories (age 0–5, 5–15 and 25–60). We found that influenza A and B were both active in winter but were not always seasonally synchronous in Beijing. Synchronization between age ranges was found in most epidemic peaks from 2008–2015. Our findings suggested that peaks of influenza-like illness in individuals aged 0–5 and 5–15 years consistently appeared ahead of those of adults, implying the possibility that schoolchildren may lead epidemic fluctuations.",2016 Dec 30,"['Wu, Zhenyu', 'Sun, Xiaoyu', 'Chu, Yanhui', 'Sun, Jingyi', 'Qin, Guoyou', 'Yang, Lin', 'Qin, Jingning', 'Xiao, Zheng', 'Ren, Jian', 'Qin, Di', 'Wang, Xiling', 'Zheng, Xueying']",PLoS One,,,True
eb6e2916b4a94b8c8a3e7d58f70158dc04191503,PMC,"Knowledge, Attitudes and Behaviours of Healthcare Workers in the Kingdom of Saudi Arabia to MERS Coronavirus and Other Emerging Infectious Diseases",http://dx.doi.org/10.3390/ijerph13121214,PMC5201355,27929452,CC BY,"Background: The Kingdom of Saudi Arabia has experienced a prolonged outbreak of Middle East Respiratory Syndrome (MERS) coronavirus since 2012. Healthcare workers (HCWs) form a significant risk group for infection. Objectives: The aim of this survey was to assess the knowledge, attitudes, infection control practices and educational needs of HCWs in the Kingdom of Saudi Arabia to MERS coronavirus and other emerging infectious diseases. Methods: 1500 of HCWs from Saudi Ministry of Health were invited to fill a questionnaire developed to cover the survey objectives from 9 September 2015 to 8 November 2015. The response rate was about 81%. Descriptive statistics was used to summarise the responses. Results: 1216 HCWs were included in this survey. A total of 56.5% were nurses and 22% were physicians. The most common sources of MERS-coronavirus (MERS-CoV) information were the Ministry of Health (MOH) memo (74.3%). Only (47.6%) of the physicians, (30.4%) of the nurses and (29.9%) of the other HCWs were aware that asymptomatic MERS-CoV was described. Around half of respondents who having been investigated for MERS-CoV reported that their work performance decreased while they have suspicion of having MERS-CoV and almost two thirds reported having psychological problems during this period. Almost two thirds of the HCWs (61.2%) reported anxiety about contracting MERS-CoV from patients. Conclusions: The knowledge about emerging infectious diseases was poor and there is need for further education and training programs particularly in the use of personal protective equipment, isolation and infection control measures. The self-reported infection control practices were sub-optimal and seem to be overestimated.",2016 Dec 6,"['Alsahafi, Abdullah J.', 'Cheng, Allen C.']",Int J Environ Res Public Health,,,True
7c8f40872fb6e8d5289fec4b0573cc22e15fa180,PMC,Military-civilian cooperative emergency response to infectious disease prevention and control in China,http://dx.doi.org/10.1186/s40779-016-0109-y,PMC5203723,28050261,CC BY,"In recent years, the incidence of severe infectious diseases has increased, and the number of emerging infectious diseases continues to increase. The Chinese government and military forces have paid a great deal of attention to infectious disease prevention and control, and using military-civilian cooperation, they have successfully prevented numerous severe epidemic situations, such as severe acute respiratory syndrome (SARS), influenza A (H1N1), avian influenza H5N1 and H7N9, and Ebola hemorrhagic fever, while actively maintained public health, economic development, and national construction. This paper focuses on the mechanisms of the military-cooperative emergency response to infectious diseases--the joint working mechanism, the information-sharing mechanism, the research collaboration mechanism, and the joint disposal mechanism--and presents a sorted summary of the practices and experiences of cooperative emergency responses to infectious diseases. In the future, the Chinese military and the civilian sector will further strengthen the cooperative joint command system and emergency rescue force and will reinforce their collaborative information-sharing platform and technical equipment system to further improve military-civilian collaborative emergency infectious diseases disposal, advance the level of infectious disease prevention and control, and maintain public health.",2016 Dec 30,"['Ma, Hui', 'Dong, Ji-Ping', 'Zhou, Na', 'Pu, Wei']",Mil Med Res,,,True
f7ddd78bba691e9200cece8a05b3486fab895885,PMC,Role of Eukaryotic Initiation Factors during Cellular Stress and Cancer Progression,http://dx.doi.org/10.1155/2016/8235121,PMC5204094,28083147,CC BY,"Protein synthesis can be segmented into distinct phases comprising mRNA translation initiation, elongation, and termination. Translation initiation is a highly regulated and rate-limiting step of protein synthesis that requires more than 12 eukaryotic initiation factors (eIFs). Extensive evidence shows that the transcriptome and corresponding proteome do not invariably correlate with each other in a variety of contexts. In particular, translation of mRNAs specific to angiogenesis, tumor development, and apoptosis is altered during physiological and pathophysiological stress conditions. In cancer cells, the expression and functions of eIFs are hampered, resulting in the inhibition of global translation and enhancement of translation of subsets of mRNAs by alternative mechanisms. A precise understanding of mechanisms involving eukaryotic initiation factors leading to differential protein expression can help us to design better strategies to diagnose and treat cancer. The high spatial and temporal resolution of translation control can have an immediate effect on the microenvironment of the cell in comparison with changes in transcription. The dysregulation of mRNA translation mechanisms is increasingly being exploited as a target to treat cancer. In this review, we will focus on this context by describing both canonical and noncanonical roles of eIFs, which alter mRNA translation.",2016 Dec 19,"['Sharma, Divya Khandige', 'Bressler, Kamiko', 'Patel, Harshil', 'Balasingam, Nirujah', 'Thakor, Nehal']",J Nucleic Acids,,,True
37bc284af4f2f731792f44339253abc79c6d2782,PMC,Host and Viral Modulation of RIG-I-Mediated Antiviral Immunity,http://dx.doi.org/10.3389/fimmu.2016.00662,PMC5206486,28096803,CC BY,"Innate immunity is the first line of defense against invading pathogens. Rapid and efficient detection of pathogen-associated molecular patterns via pattern-recognition receptors is essential for the host to mount defensive and protective responses. Retinoic acid-inducible gene-I (RIG-I) is critical in triggering antiviral and inflammatory responses for the control of viral replication in response to cytoplasmic virus-specific RNA structures. Upon viral RNA recognition, RIG-I recruits the mitochondrial adaptor protein mitochondrial antiviral signaling protein, which leads to a signaling cascade that coordinates the induction of type I interferons (IFNs), as well as a large variety of antiviral interferon-stimulated genes. The RIG-I activation is tightly regulated via various posttranslational modifications for the prevention of aberrant innate immune signaling. By contrast, viruses have evolved mechanisms of evasion, such as sequestrating viral structures from RIG-I detections and targeting receptor or signaling molecules for degradation. These virus–host interactions have broadened our understanding of viral pathogenesis and provided insights into the function of the RIG-I pathway. In this review, we summarize the recent advances regarding RIG-I pathogen recognition and signaling transduction, cell-intrinsic control of RIG-I activation, and the viral antagonism of RIG-I signaling.",2017 Jan 3,"['Liu, Yiliu', 'Olagnier, David', 'Lin, Rongtuan']",Front Immunol,,,True
4328e18bdf9b52875c87f3f5ddb1911636a192d2,PMC,"Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome",http://dx.doi.org/10.3389/fimmu.2016.00535,PMC5206578,28096800,CC BY,"Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Previous studies have identified interferon-induced transmembrane proteins (IFITMs) as an interferon-stimulated gene family. However, the role of IFITMs in HTNV infection is unclear. In this study, we observed that IFITM3 single nucleotide polymorphisms (SNP) rs12252 C allele and CC genotype associated with the disease severity and HTNV load in the plasma of HFRS patients. In vitro experiments showed that the truncated protein produced by the rs12252 C allele exhibited an impaired anti-HTNV activity. We also proved that IFITM3 was able to inhibit HTNV infection in both HUVEC and A549 cells by overexpression and RNAi assays, likely via a mechanism of inhibiting virus entry demonstrated by binding and entry assay. Localization of IFITM3 in late endosomes was also observed. In addition, we demonstrated that the transcription of IFITM3 is negatively regulated by an lncRNA negative regulator of interferon response (NRIR). Taken together, we conclude that IFITM3, negatively regulated by NRIR, inhibits HTNV infection, and its SNP rs12252 correlates with the plasma HTNV load and the disease severity of patients with HFRS.",2017 Jan 3,"['Xu-yang, Zheng', 'Pei-yu, Bian', 'Chuan-tao, Ye', 'Wei, Ye', 'Hong-wei, Ma', 'Kang, Tang', 'Chun-mei, Zhang', 'Ying-feng, Lei', 'Xin, Wei', 'Ping-zhong, Wang', 'Chang-xing, Huang', 'Xue-fan, Bai', 'Ying, Zhang', 'Zhan-sheng, Jia']",Front Immunol,,,True
76260c67421abbf69da3c4b0c75204190188a2cc,PMC,"Nucleocapsid Interacts with NPM1 and Protects it from Proteolytic Cleavage, Enhancing Cell Survival, and is Involved in PEDV Growth",http://dx.doi.org/10.1038/srep39700,PMC5206633,28045037,CC BY,"Porcine epidemic diarrhea virus (PEDV) replicates in the cytoplasm of infected cells, but its nucleocapsid (N) protein localizes specifically to the nucleolus. The mechanism of nuclear translocation, and whether N protein associates with particular nucleolar components, is unknown. In this study, we confirm that a nucleolar phosphoprotein nucleophosmin (NPM1) interacts and co-localizes with the N protein in the nucleolus. In vitro binding studies indicated that aa 148–294 of N and aa 118–188 of NPM1 were required for binding. Interestingly, N protein importation into the nucleolus is independent of the ability of NPM1 to shuttle between the nucleus and the cytoplasm. Furthermore, overexpression of NPM1 promoted PEDV growth, while knockdown of NPM1 suppressed PEDV growth. In addition, binding of N protein to NPM1 protects it from proteolytic degradation by caspase-3, leading to increased cell survival. Taken together, our studies demonstrate a specific interaction of the N protein with the host cell protein NPM1 in the nucleolus. The results suggest potential linkages among viral strategies for the regulation of cell survival activities, possibly through an interaction of N protein with NPM1 which prevents its proteolytic cleavage and enhances cell survival, thus ultimately promoting the replication of PEDV.",2017 Jan 3,"['Shi, Da', 'Shi, Hongyan', 'Sun, Dongbo', 'Chen, Jianfei', 'Zhang, Xin', 'Wang, Xiaobo', 'Zhang, Jialin', 'Ji, Zhaoyang', 'Liu, Jianbo', 'Cao, Liyan', 'Zhu, Xiangdong', 'Yuan, Jing', 'Dong, Hui', 'Wang, Xin', 'Chang, Tiecheng', 'Liu, Ye', 'Feng, Li']",Sci Rep,,,True
77e4762b5cc01adc2c17ddfe8e4de0a8036f4821,PMC,"Nucleocapsid Interacts with NPM1 and Protects it from Proteolytic Cleavage, Enhancing Cell Survival, and is Involved in PEDV Growth",http://dx.doi.org/10.1038/srep39700,PMC5206633,28045037,CC BY,"Porcine epidemic diarrhea virus (PEDV) replicates in the cytoplasm of infected cells, but its nucleocapsid (N) protein localizes specifically to the nucleolus. The mechanism of nuclear translocation, and whether N protein associates with particular nucleolar components, is unknown. In this study, we confirm that a nucleolar phosphoprotein nucleophosmin (NPM1) interacts and co-localizes with the N protein in the nucleolus. In vitro binding studies indicated that aa 148–294 of N and aa 118–188 of NPM1 were required for binding. Interestingly, N protein importation into the nucleolus is independent of the ability of NPM1 to shuttle between the nucleus and the cytoplasm. Furthermore, overexpression of NPM1 promoted PEDV growth, while knockdown of NPM1 suppressed PEDV growth. In addition, binding of N protein to NPM1 protects it from proteolytic degradation by caspase-3, leading to increased cell survival. Taken together, our studies demonstrate a specific interaction of the N protein with the host cell protein NPM1 in the nucleolus. The results suggest potential linkages among viral strategies for the regulation of cell survival activities, possibly through an interaction of N protein with NPM1 which prevents its proteolytic cleavage and enhances cell survival, thus ultimately promoting the replication of PEDV.",2017 Jan 3,"['Shi, Da', 'Shi, Hongyan', 'Sun, Dongbo', 'Chen, Jianfei', 'Zhang, Xin', 'Wang, Xiaobo', 'Zhang, Jialin', 'Ji, Zhaoyang', 'Liu, Jianbo', 'Cao, Liyan', 'Zhu, Xiangdong', 'Yuan, Jing', 'Dong, Hui', 'Wang, Xin', 'Chang, Tiecheng', 'Liu, Ye', 'Feng, Li']",Sci Rep,,,False
367af6bb9a8bbda02206506a819656bb6f14ce4c,PMC,Logistics of community smallpox control through contact tracing and ring vaccination: a stochastic network model,http://dx.doi.org/10.1186/1471-2458-4-34,PMC520756,15298713,CC BY,"BACKGROUND: Previous smallpox ring vaccination models based on contact tracing over a network suggest that ring vaccination would be effective, but have not explicitly included response logistics and limited numbers of vaccinators. METHODS: We developed a continuous-time stochastic simulation of smallpox transmission, including network structure, post-exposure vaccination, vaccination of contacts of contacts, limited response capacity, heterogeneity in symptoms and infectiousness, vaccination prior to the discontinuation of routine vaccination, more rapid diagnosis due to public awareness, surveillance of asymptomatic contacts, and isolation of cases. RESULTS: We found that even in cases of very rapidly spreading smallpox, ring vaccination (when coupled with surveillance) is sufficient in most cases to eliminate smallpox quickly, assuming that 95% of household contacts are traced, 80% of workplace or social contacts are traced, and no casual contacts are traced, and that in most cases the ability to trace 1–5 individuals per day per index case is sufficient. If smallpox is assumed to be transmitted very quickly to contacts, it may at times escape containment by ring vaccination, but could be controlled in these circumstances by mass vaccination. CONCLUSIONS: Small introductions of smallpox are likely to be easily contained by ring vaccination, provided contact tracing is feasible. Uncertainties in the nature of bioterrorist smallpox (infectiousness, vaccine efficacy) support continued planning for ring vaccination as well as mass vaccination. If initiated, ring vaccination should be conducted without delays in vaccination, should include contacts of contacts (whenever there is sufficient capacity) and should be accompanied by increased public awareness and surveillance.",2004 Aug 6,"['Porco, Travis C', 'Holbrook, Karen A', 'Fernyak, Susan E', 'Portnoy, Diane L', 'Reiter, Randy', 'Aragón, Tomás J']",BMC Public Health,,,True
638e94413019416e1f60f942e1870ac8e9cc4a3a,PMC,Logistics of community smallpox control through contact tracing and ring vaccination: a stochastic network model,http://dx.doi.org/10.1186/1471-2458-4-34,PMC520756,15298713,CC BY,"BACKGROUND: Previous smallpox ring vaccination models based on contact tracing over a network suggest that ring vaccination would be effective, but have not explicitly included response logistics and limited numbers of vaccinators. METHODS: We developed a continuous-time stochastic simulation of smallpox transmission, including network structure, post-exposure vaccination, vaccination of contacts of contacts, limited response capacity, heterogeneity in symptoms and infectiousness, vaccination prior to the discontinuation of routine vaccination, more rapid diagnosis due to public awareness, surveillance of asymptomatic contacts, and isolation of cases. RESULTS: We found that even in cases of very rapidly spreading smallpox, ring vaccination (when coupled with surveillance) is sufficient in most cases to eliminate smallpox quickly, assuming that 95% of household contacts are traced, 80% of workplace or social contacts are traced, and no casual contacts are traced, and that in most cases the ability to trace 1–5 individuals per day per index case is sufficient. If smallpox is assumed to be transmitted very quickly to contacts, it may at times escape containment by ring vaccination, but could be controlled in these circumstances by mass vaccination. CONCLUSIONS: Small introductions of smallpox are likely to be easily contained by ring vaccination, provided contact tracing is feasible. Uncertainties in the nature of bioterrorist smallpox (infectiousness, vaccine efficacy) support continued planning for ring vaccination as well as mass vaccination. If initiated, ring vaccination should be conducted without delays in vaccination, should include contacts of contacts (whenever there is sufficient capacity) and should be accompanied by increased public awareness and surveillance.",2004 Aug 6,"['Porco, Travis C', 'Holbrook, Karen A', 'Fernyak, Susan E', 'Portnoy, Diane L', 'Reiter, Randy', 'Aragón, Tomás J']",BMC Public Health,,,False
55d7f70ed1547d9c2708ffb08ae515d54de510fb,PMC,Logistics of community smallpox control through contact tracing and ring vaccination: a stochastic network model,http://dx.doi.org/10.1186/1471-2458-4-34,PMC520756,15298713,CC BY,"BACKGROUND: Previous smallpox ring vaccination models based on contact tracing over a network suggest that ring vaccination would be effective, but have not explicitly included response logistics and limited numbers of vaccinators. METHODS: We developed a continuous-time stochastic simulation of smallpox transmission, including network structure, post-exposure vaccination, vaccination of contacts of contacts, limited response capacity, heterogeneity in symptoms and infectiousness, vaccination prior to the discontinuation of routine vaccination, more rapid diagnosis due to public awareness, surveillance of asymptomatic contacts, and isolation of cases. RESULTS: We found that even in cases of very rapidly spreading smallpox, ring vaccination (when coupled with surveillance) is sufficient in most cases to eliminate smallpox quickly, assuming that 95% of household contacts are traced, 80% of workplace or social contacts are traced, and no casual contacts are traced, and that in most cases the ability to trace 1–5 individuals per day per index case is sufficient. If smallpox is assumed to be transmitted very quickly to contacts, it may at times escape containment by ring vaccination, but could be controlled in these circumstances by mass vaccination. CONCLUSIONS: Small introductions of smallpox are likely to be easily contained by ring vaccination, provided contact tracing is feasible. Uncertainties in the nature of bioterrorist smallpox (infectiousness, vaccine efficacy) support continued planning for ring vaccination as well as mass vaccination. If initiated, ring vaccination should be conducted without delays in vaccination, should include contacts of contacts (whenever there is sufficient capacity) and should be accompanied by increased public awareness and surveillance.",2004 Aug 6,"['Porco, Travis C', 'Holbrook, Karen A', 'Fernyak, Susan E', 'Portnoy, Diane L', 'Reiter, Randy', 'Aragón, Tomás J']",BMC Public Health,,,False
be050658bf3b654ae5d9cbe62f6198e5c4932a95,PMC,"Recombinase Polymerase Amplification Assay—A Simple, Fast and Cost-Effective Alternative to Real Time PCR for Specific Detection of Feline Herpesvirus-1",http://dx.doi.org/10.1371/journal.pone.0166903,PMC5207716,28045956,CC BY,"Feline herpesvirus 1 (FHV-1), an enveloped dsDNA virus, is one of the major pathogens of feline upper respiratory tract disease (URTD) and ocular disease. Currently, polymerase chain reaction (PCR) remains the gold standard diagnostic tool for FHV-1 infection but is relatively expensive, requires well-equipped laboratories and is not suitable for field tests. Recombinase polymerase amplification (RPA), an isothermal gene amplification technology, has been explored for the molecular diagnosis of infectious diseases. In this study, an exo-RPA assay for FHV-1 detection was developed and validated. Primers targeting specifically the thymidine kinase (TK) gene of FHV-1 were designed. The RPA reaction was performed successfully at 39°C and the results were obtained within 20 min. Using different copy numbers of recombinant plasmid DNA that contains the TK gene as template, we showed the detection limit of exo-RPA was 10(2) copies DNA/reaction, the same as that of real time PCR. The exo-RPA assay did not cross-detect feline panleukopenia virus, feline calicivirus, bovine herpesvirus-1, pseudorabies virus or chlamydia psittaci, a panel of pathogens important in feline URTD or other viruses in Alphaherpesvirinae, demonstrating high specificity. The assay was validated by testing 120 nasal and ocular conjunctival swabs of cats, and the results were compared with those obtained with real-time PCR. Both assays provided the same testing results in the clinical samples. Compared with real time PCR, the exo-RPA assay uses less-complex equipment that is portable and the reaction is completed much faster. Additionally, commercial RPA reagents in vacuum-sealed pouches can tolerate temperatures up to room temperature for days without loss of activity, suitable for shipment and storage for field tests. Taken together, the exo-RPA assay is a simple, fast and cost-effective alternative to real time PCR, suitable for use in less advanced laboratories and for field detection of FHV-1 infection.",2017 Jan 3,"['Wang, Jianchang', 'Liu, Libing', 'Wang, Jinfeng', 'Sun, Xiaoxia', 'Yuan, Wanzhe']",PLoS One,,,True
7314f2ac32ead26d507b36cd305ffd76736f1007,PMC,Deep sequencing reveals persistence of cell-associated mumps vaccine virus in chronic encephalitis,http://dx.doi.org/10.1007/s00401-016-1629-y,PMC5209397,27770235,CC BY,"Routine childhood vaccination against measles, mumps and rubella has virtually abolished virus-related morbidity and mortality. Notwithstanding this, we describe here devastating neurological complications associated with the detection of live-attenuated mumps virus Jeryl Lynn (MuV(JL5)) in the brain of a child who had undergone successful allogeneic transplantation for severe combined immunodeficiency (SCID). This is the first confirmed report of MuV(JL5) associated with chronic encephalitis and highlights the need to exclude immunodeficient individuals from immunisation with live-attenuated vaccines. The diagnosis was only possible by deep sequencing of the brain biopsy. Sequence comparison of the vaccine batch to the MuV(JL5) isolated from brain identified biased hypermutation, particularly in the matrix gene, similar to those found in measles from cases of SSPE. The findings provide unique insights into the pathogenesis of paramyxovirus brain infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-016-1629-y) contains supplementary material, which is available to authorized users.",2017 Oct 21,"['Morfopoulou, Sofia', 'Mee, Edward T.', 'Connaughton, Sarah M.', 'Brown, Julianne R.', 'Gilmour, Kimberly', 'Chong, WK ‘Kling’', 'Duprex, W. Paul', 'Ferguson, Deborah', 'Hubank, Mike', 'Hutchinson, Ciaran', 'Kaliakatsos, Marios', 'McQuaid, Stephen', 'Paine, Simon', 'Plagnol, Vincent', 'Ruis, Christopher', 'Virasami, Alex', 'Zhan, Hong', 'Jacques, Thomas S.', 'Schepelmann, Silke', 'Qasim, Waseem', 'Breuer, Judith']",Acta Neuropathol,,,True
72aaf5f39ed048ee9ebda9af6fba6d6d12082e68,PMC,Versatility of Approximating Single-Particle Electron Microscopy Density Maps Using Pseudoatoms and Approximation-Accuracy Control,http://dx.doi.org/10.1155/2016/7060348,PMC5209604,28097146,CC BY,"Three-dimensional Gaussian functions have been shown useful in representing electron microscopy (EM) density maps for studying macromolecular structure and dynamics. Methods that require setting a desired number of Gaussian functions or a maximum number of iterations may result in suboptimal representations of the structure. An alternative is to set a desired error of approximation of the given EM map and then optimize the number of Gaussian functions to achieve this approximation error. In this article, we review different applications of such an approach that uses spherical Gaussian functions of fixed standard deviation, referred to as pseudoatoms. Some of these applications use EM-map normal mode analysis (NMA) with elastic network model (ENM) (applications such as predicting conformational changes of macromolecular complexes or exploring actual conformational changes by normal-mode-based analysis of experimental data) while some other do not use NMA (denoising of EM density maps). In applications based on NMA and ENM, the advantage of using pseudoatoms in EM-map coarse-grain models is that the ENM springs are easily assigned among neighboring grains thanks to their spherical shape and uniformed size. EM-map denoising based on the map coarse-graining was so far only shown using pseudoatoms as grains.",2016 Dec 21,"['Jonić, Slavica', 'Sorzano, Carlos Oscar S.']",Biomed Res Int,,,True
c936ef4688d255c47855066ca55d95f4dfc227e0,PMC,Universal and reusable virus deactivation system for respiratory protection,http://dx.doi.org/10.1038/srep39956,PMC5209731,28051158,CC BY,"Aerosolized pathogens are a leading cause of respiratory infection and transmission. Currently used protective measures pose potential risk of primary/secondary infection and transmission. Here, we report the development of a universal, reusable virus deactivation system by functionalization of the main fibrous filtration unit of surgical mask with sodium chloride salt. The salt coating on the fiber surface dissolves upon exposure to virus aerosols and recrystallizes during drying, destroying the pathogens. When tested with tightly sealed sides, salt-coated filters showed remarkably higher filtration efficiency than conventional mask filtration layer, and 100% survival rate was observed in mice infected with virus penetrated through salt-coated filters. Viruses captured on salt-coated filters exhibited rapid infectivity loss compared to gradual decrease on bare filters. Salt-coated filters proved highly effective in deactivating influenza viruses regardless of subtypes and following storage in harsh environmental conditions. Our results can be applied in obtaining a broad-spectrum, airborne pathogen prevention device in preparation for epidemic and pandemic of respiratory diseases.",2017 Jan 4,"['Quan, Fu-Shi', 'Rubino, Ilaria', 'Lee, Su-Hwa', 'Koch, Brendan', 'Choi, Hyo-Jick']",Sci Rep,,,True
a606413c3dd48c1755b453abeaa1c62702aba67e,PMC,Universal and reusable virus deactivation system for respiratory protection,http://dx.doi.org/10.1038/srep39956,PMC5209731,28051158,CC BY,"Aerosolized pathogens are a leading cause of respiratory infection and transmission. Currently used protective measures pose potential risk of primary/secondary infection and transmission. Here, we report the development of a universal, reusable virus deactivation system by functionalization of the main fibrous filtration unit of surgical mask with sodium chloride salt. The salt coating on the fiber surface dissolves upon exposure to virus aerosols and recrystallizes during drying, destroying the pathogens. When tested with tightly sealed sides, salt-coated filters showed remarkably higher filtration efficiency than conventional mask filtration layer, and 100% survival rate was observed in mice infected with virus penetrated through salt-coated filters. Viruses captured on salt-coated filters exhibited rapid infectivity loss compared to gradual decrease on bare filters. Salt-coated filters proved highly effective in deactivating influenza viruses regardless of subtypes and following storage in harsh environmental conditions. Our results can be applied in obtaining a broad-spectrum, airborne pathogen prevention device in preparation for epidemic and pandemic of respiratory diseases.",2017 Jan 4,"['Quan, Fu-Shi', 'Rubino, Ilaria', 'Lee, Su-Hwa', 'Koch, Brendan', 'Choi, Hyo-Jick']",Sci Rep,,,False
e594dcc4d1864621d24cc6ffbc70a88a5ae1207d,PMC,An assessment of the level of concern among hospital-based health-care workers regarding MERS outbreaks in Saudi Arabia,http://dx.doi.org/10.1186/s12879-016-2096-8,PMC5210292,28049440,CC BY,"BACKGROUND: Middle East Respiratory Syndrome (MERS) is caused by MERS coronavirus (MERS-CoV). More than 80% of reported cases have occurred in Saudi Arabia, with a mortality exceeding 50%. Health-care workers (HCWs) are at risk of acquiring and transmitting this virus, so the concerns of HCWs in Saudi Arabia regarding MERS were evaluated. METHODS: An anonymous, self-administered, previously validated questionnaire was given to 1031 HCWs at three tertiary hospitals in Saudi Arabia from October to December, 2014. Concerns regarding the disease, its severity and governmental efforts to contain it, as well as disease outcomes were assessed using 31 concern statements in five distinct domains. A total concern score was calculated for each HCW. Multiple regression analyses were used to identify predictors of high concern scores. RESULTS: The average age of participants was 37.1 ± 9.0 years, 65.8% were married and 59.1% were nurses. The majority of respondents (70.4%) felt at risk of contracting a MERS-CoV infection at work, 69.1% felt threatened if a colleague contracted MERS-CoV, 60.9% felt obliged to care for patients infected with MERS-CoV and 87.8% did not feel safe at work using standard precautions. In addition, 87.7% believed that the government should isolate patients with MERS in specialized hospitals, 73.7% agreed with travel restriction to and from areas affected by MERS and 65.3% agreed with avoiding inviting expatriates from such areas. After adjustment for covariates, high concern scores were significantly associated with being a Saudi national (p < 0.001), a non-physician (p < 0.001) and working in the central region (p < 0.001). CONCLUSIONS: The majority of respondents reported concern regarding MERS-CoV infection from exposure at work. The overall level of concern may be influenced by previous experience of MERS outbreaks and related cultural issues. The concerns of HCWs may affect their overall effectiveness in an outbreak and should be addressed by incorporating management strategies in outbreak planning.",2017 Jan 3,"['Abolfotouh, Mostafa A.', 'AlQarni, Ali A.', 'Al-Ghamdi, Suliman M.', 'Salam, Mahmoud', 'Al-Assiri, Mohammed H.', 'Balkhy, Hanan H.']",BMC Infect Dis,,,True
d58edd47f5a609373fc4fbfd0b3cb4dfcec173c3,PMC,BreathDx – molecular analysis of exhaled breath as a diagnostic test for ventilator–associated pneumonia: protocol for a European multicentre observational study,http://dx.doi.org/10.1186/s12890-016-0353-7,PMC5210294,28049457,CC BY,"BACKGROUND: The diagnosis of ventilator-associated pneumonia (VAP) remains time-consuming and costly, the clinical tools lack specificity and a bedside test to exclude infection in suspected patients is unavailable. Breath contains hundreds to thousands of volatile organic compounds (VOCs) that result from host and microbial metabolism as well as the environment. The present study aims to use breath VOC analysis to develop a model that can discriminate between patients who have positive cultures and who have negative cultures with a high sensitivity. METHODS/DESIGN: The Molecular Analysis of Exhaled Breath as Diagnostic Test for Ventilator-Associated Pneumonia (BreathDx) study is a multicentre observational study. Breath and bronchial lavage samples will be collected from 100 and 53 intubated and ventilated patients suspected of VAP. Breath will be analysed using Thermal Desorption – Gas Chromatography – Mass Spectrometry (TD-GC-MS). The primary endpoint is the accuracy of cross-validated prediction for positive respiratory cultures in patients that are suspected of VAP, with a sensitivity of at least 99% (high negative predictive value). DISCUSSION: To our knowledge, BreathDx is the first study powered to investigate whether molecular analysis of breath can be used to classify suspected VAP patients with and without positive microbiological cultures with 99% sensitivity. TRIAL REGISTRATION: UKCRN ID number 19086, registered May 2015; as well as registration at www.trialregister.nl under the acronym ‘BreathDx’ with trial ID number NTR 6114 (retrospectively registered on 28 October 2016).",2017 Jan 3,"['van Oort, Pouline M. P.', 'Nijsen, Tamara', 'Weda, Hans', 'Knobel, Hugo', 'Dark, Paul', 'Felton, Timothy', 'Rattray, Nicholas J. W.', 'Lawal, Oluwasola', 'Ahmed, Waqar', 'Portsmouth, Craig', 'Sterk, Peter J.', 'Schultz, Marcus J.', 'Zakharkina, Tetyana', 'Artigas, Antonio', 'Povoa, Pedro', 'Martin-Loeches, Ignacio', 'Fowler, Stephen J.', 'Bos, Lieuwe D. J.', None]",BMC Pulm Med,,,True
9a512204e9b43d11f12458baaa3db5cb71e5ae16,PMC,"De novo transcriptome assembly and characterization of nine tissues of Lonicera japonica to identify potential candidate genes involved in chlorogenic acid, luteolosides, and secoiridoid biosynthesis pathways",http://dx.doi.org/10.1007/s11418-016-1041-x,PMC5214891,27629269,CC BY,"Lonicera japonica is one of the most important medicinal plants with applications in traditional Chinese and Japanese medicine for thousands of years. Extensive studies on the constituents of L. japonica extracts have revealed an accumulation of pharmaceutically active metabolite classes, such as chlorogenic acid, luteolin and other flavonoids, and secoiridoids, which impart characteristic medicinal properties. Despite being a rich source of pharmaceutically active metabolites, little is known about the biosynthetic enzymes involved, and their expression profile across different tissues of L. japonica. In this study, we performed de novo transcriptome assembly for L. japonica, representing transcripts from nine different tissues. A total of 22 Gbps clean RNA-seq reads from nine tissues of L. japonica were used, resulting in 243,185 unigenes, with 99,938 unigenes annotated based on a homology search using blastx against the NCBI-nr protein database. Unsupervised principal component analysis and correlation studies using transcript expression data from all nine tissues of L. japonica showed relationships between tissues, explaining their association at different developmental stages. Homologs for all genes associated with chlorogenic acid, luteolin, and secoiridoid biosynthesis pathways were identified in the L. japonica transcriptome assembly. Expression of unigenes associated with chlorogenic acid was enriched in stems and leaf-2, unigenes from luteolin were enriched in stems and flowers, while unigenes from secoiridoid metabolic pathways were enriched in leaf-1 and shoot apex. Our results showed that different tissues of L. japonica are enriched with sets of unigenes associated with specific pharmaceutically important metabolic pathways and, therefore, possess unique medicinal properties. The present study will serve as a resource for future attempts for functional characterization of enzyme coding genes within key metabolic processes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11418-016-1041-x) contains supplementary material, which is available to authorized users.",2017 Sep 14,"['Rai, Amit', 'Kamochi, Hidetaka', 'Suzuki, Hideyuki', 'Nakamura, Michimi', 'Takahashi, Hiroki', 'Hatada, Tomoki', 'Saito, Kazuki', 'Yamazaki, Mami']",J Nat Med,,,True
229bb9dc175fcc4d90e46d9ad90b67ab3e49a536,PMC,Virion Background and Efficiency of Virion Incorporation Determine Susceptibility of Simian Immunodeficiency Virus Env-Driven Viral Entry to Inhibition by IFITM Proteins,http://dx.doi.org/10.1128/JVI.01488-16,PMC5215347,27807233,CC BY,"Interferon-induced transmembrane proteins (IFITMs) can inhibit the cellular entry of several enveloped viruses, including simian immunodeficiency virus (SIV). The blockade of SIV by IFITMs is isolate specific, raising the question of which parameters impact sensitivity to IFITM. We show that the virion context in which SIV-Env is presented and the efficiency of virion incorporation determine Env susceptibility to inhibition by IFITMs. Thus, determinants other than the nature of the envelope protein can impact the IFITM sensitivity of viral entry. IMPORTANCE The host cell-encoded IFITM proteins can block viral entry and are an important component of the innate defenses against viral infection. However, the determinants controlling whether a virus is susceptible to blockade by IFITM proteins are incompletely understood. Our study shows that the amount of envelope proteins incorporated into virions as well as the nature of the virion particle itself can impact the sensitivity of viral entry to IFITMs. These results show for the first time that determinants other than the viral envelope protein can impact sensitivity to IFITM and have implications for the interpretation of previously published data on inhibition of viruses by IFITM proteins. Moreover, our findings might help to define the mechanism underlying the antiviral activity of IFITM proteins.",2017 Jan 3,"['Wrensch, Florian', 'Hoffmann, Markus', 'Gärtner, Sabine', 'Nehlmeier, Inga', 'Winkler, Michael', 'Pöhlmann, Stefan']",J Virol,,,True
99cbce9d58b005643a2402b10d8ec96ec8aea7c9,PMC,Improvement and Evaluation of Loop-Mediated Isothermal Amplification for Rapid Detection of Toxoplasma gondii Infection in Human Blood Samples,http://dx.doi.org/10.1371/journal.pone.0169125,PMC5215908,28056092,CC BY,"Loop-mediated isothermal amplification (LAMP), an attractive DNA amplification method, was developed as a valuable tool for the rapid detection of Toxoplasma gondii. In this study, species-specific LAMP primers were designed by targeting the AF146527 sequence, which was a conserved sequence of 200- to 300-fold repetitive 529 bp fragment of T.gondii. LAMP reaction system was optimized so that it could detect the minimal DNA sample such as a single tachyzoite or 10 copies of recombinant plasmid. No cross-reactivity was found when using DNA from other parasites as templates. Subsequently, a total of 200 human blood samples were directly investigated by two diagnostic methods, LAMP and conventional PCR. Fourteen of 200 (7%) samples were positive for Toxoplasma by LAMP (the primers developed in this study), whereas only 5 of 200 (2.5%) were proved positive by conventional PCR. The procedure of the LAMP assay was very simple, as the reaction would be carried out in a single tube under isothermal conditions at 64°C and the result would be read out with 1 h (as early as 35 min with loop primers). Thus, this method has the advantages of rapid amplification, simple operation, and easy detection and would be useful for rapid and reliable clinical diagnosis of acute toxoplasmosis, especially in developing countries.",2017 Jan 5,"['Sun, Xi-meng', 'Ji, Yong-sheng', 'Liu, Xian-yong', 'Xiang, Mei', 'He, Guang', 'Xie, Li', 'Suo, Jing-xia', 'Suo, Xun']",PLoS One,,,True
b9774fe2b5e6e752ff1e59bd6b2e46d7815b4a49,PMC,Outbreak of Middle East respiratory syndrome coronavirus in Saudi Arabia: a retrospective study,http://dx.doi.org/10.1186/s12879-016-2137-3,PMC5217314,28056850,CC BY,"BACKGROUND: The Middle East respiratory syndrome (MERS) is proposed to be a zoonotic disease. Dromedary camels have been implicated due to reports that some confirmed cases were exposed to camels. Risk factors for MERS coronavirus (MERS-CoV) infections in humans are incompletely understood. This study aimed to describe the demographic characteristics, mortality rate, clinical manifestations and comorbidities with confirmed cases of MERS-CoV. METHODS: Retrospective chart review were performed to identify all laboratory-confirmed cases of MERS-CoV in Saudi Arabia who reported to the Ministry of Health (MOH) of Saudi Arabia and WHO between April 23, 2014 and August 31, 2015. Patients’ charts were also reviewed for demographic information, mortality, comorbidities, clinical presentations, health care facility and presented with descriptive and comparative statistics using non parametric binomial test and Chi-square test. RESULTS: Confirmed cases of male patients (61.1%) exceeded those of female patients (38.9%). Infections among Saudi patients (62.6%) exceeded those among non-Saudi patients (37.4%; P = 0.001). The majority of the patients were aged 21–40 years (37.4%) or 41–60 years (35.8%); 43 (22.6%) were aged >61 years, and (8) 4.2% were aged 0–20 years. There was a difference in mortality between confirmed MERS-CoV cases (63.7% alive versus 36.3% dead cases, respectively). Furthermore, fever with cough and shortness of breath (SOB) (n = 39; 20.5%), fever with cough (n = 29; 15.3%), fever (n = 18; 9.5%), and fever with SOB (n = 13; 6.8%), were the most common clinical manifestations associated with confirmed MERS-CoV cases. CONCLUSION: MERS-CoV is considered an epidemic in Saudi Arabia. The results of the present study showed that the frequency of cases is higher among men than women, in Saudi patients than non-Saudi, and those between 21 to 60 years are most affected. Further studies are required to improve the surveillance associated with MERS-CoV to get definite and clear answers and better understanding of the MERS-CoV outbreak as well the source, and route of infection transmission in Saudi Arabia.",2017 Jan 5,"['Aleanizy, Fadilah Sfouq', 'Mohmed, Nahla', 'Alqahtani, Fulwah Y.', 'El Hadi Mohamed, Rania Ali']",BMC Infect Dis,,,True
914b5fc6d3984b981a1e36e545cc2a74e3fbd58a,PMC,Antiviral activity of animal venom peptides and related compounds,http://dx.doi.org/10.1186/s40409-016-0089-0,PMC5217322,28074089,CC BY,"Viruses exhibit rapid mutational capacity to trick and infect host cells, sometimes assisted through virus-coded peptides that counteract host cellular immune defense. Although a large number of compounds have been identified as inhibiting various viral infections and disease progression, it is urgent to achieve the discovery of more effective agents. Furthermore, proportionally to the great variety of diseases caused by viruses, very few viral vaccines are available, and not all are efficient. Thus, new antiviral substances obtained from natural products have been prospected, including those derived from venomous animals. Venoms are complex mixtures of hundreds of molecules, mostly peptides, that present a large array of biological activities and evolved to putatively target the biochemical machinery of different pathogens or host cellular structures. In addition, non-venomous compounds, such as some body fluids of invertebrate organisms, exhibit antiviral activity. This review provides a panorama of peptides described from animal venoms that present antiviral activity, thereby reinforcing them as important tools for the development of new therapeutic drugs.",2017 Jan 6,"['da Mata, Élida Cleyse Gomes', 'Mourão, Caroline Barbosa Farias', 'Rangel, Marisa', 'Schwartz, Elisabeth Ferroni']",J Venom Anim Toxins Incl Trop Dis,,,True
5a616c081f34c8ead17742a91a121ae167d77e17,PMC,A Review of Functional Motifs Utilized by Viruses,http://dx.doi.org/10.3390/proteomes4010003,PMC5217368,28248213,CC BY,"Short linear motifs (SLiM) are short peptides that facilitate protein function and protein-protein interactions. Viruses utilize these motifs to enter into the host, interact with cellular proteins, or egress from host cells. Studying functional motifs may help to predict protein characteristics, interactions, or the putative cellular role of a protein. In virology, it may reveal aspects of the virus tropism and help find antiviral therapeutics. This review highlights the recent understanding of functional motifs utilized by viruses. Special attention was paid to the function of proteins harboring these motifs, and viruses encoding these proteins. The review highlights motifs involved in (i) immune response and post-translational modifications (e.g., ubiquitylation, SUMOylation or ISGylation); (ii) virus-host cell interactions, including virus attachment, entry, fusion, egress and nuclear trafficking; (iii) virulence and antiviral activities; (iv) virion structure; and (v) low-complexity regions (LCRs) or motifs enriched with residues (Xaa-rich motifs).",2016 Jan 21,"Sobhy, Haitham",Proteomes,,,True
82009d2b6ae6ffc4372b1d4ecc9cfa7037cb8aa0,PMC,A Review of Functional Motifs Utilized by Viruses,http://dx.doi.org/10.3390/proteomes4010003,PMC5217368,28248213,CC BY,"Short linear motifs (SLiM) are short peptides that facilitate protein function and protein-protein interactions. Viruses utilize these motifs to enter into the host, interact with cellular proteins, or egress from host cells. Studying functional motifs may help to predict protein characteristics, interactions, or the putative cellular role of a protein. In virology, it may reveal aspects of the virus tropism and help find antiviral therapeutics. This review highlights the recent understanding of functional motifs utilized by viruses. Special attention was paid to the function of proteins harboring these motifs, and viruses encoding these proteins. The review highlights motifs involved in (i) immune response and post-translational modifications (e.g., ubiquitylation, SUMOylation or ISGylation); (ii) virus-host cell interactions, including virus attachment, entry, fusion, egress and nuclear trafficking; (iii) virulence and antiviral activities; (iv) virion structure; and (v) low-complexity regions (LCRs) or motifs enriched with residues (Xaa-rich motifs).",2016 Jan 21,"Sobhy, Haitham",Proteomes,,,False
7e4905089dd52ffd586f780d272e2cd951457196,PMC,Understanding the early dynamics of the 2014 porcine epidemic diarrhea virus (PEDV) outbreak in Ontario using the incidence decay and exponential adjustment (IDEA) model,http://dx.doi.org/10.1186/s12917-016-0922-2,PMC5217418,28056953,CC BY,"BACKGROUND: The United States swine industry was first confronted with porcine epidemic diarrhea virus (PEDV) in 2013. In young pigs, the virus is highly pathogenic and the associated morbidity and mortality has a significant negative impact on the swine industry. We have applied the IDEA model to better understand the 2014 PEDV outbreak in Ontario, Canada. Using our simple, 2-parameter IDEA model, we have evaluated the early epidemic dynamics of PEDV on Ontario swine farms. RESULTS: We estimated the best-fit R(0) and control parameter (d) for the between farm transmission component of the outbreak by fitting the model to publically available cumulative incidence data. We used maximum likelihood to compare model fit estimates for different combinations of the R(0) and d parameters. Using our initial findings from the iterative fitting procedure, we projected the time course of the epidemic using only a subset of the early epidemic data. The IDEA model projections showed excellent agreement with the observed data based on a 7-day generation time estimate. The best-fit estimate for R(0) was 1.87 (95% CI: 1.52 – 2.34) and for the control parameter (d) was 0.059 (95% CI: 0.022 – 0.117). Using data from the first three generations of the outbreak, our iterative fitting procedure suggests that R(0) and d had stabilized sufficiently to project the time course of the outbreak with reasonable accuracy. CONCLUSIONS: The emergence and spread of PEDV represents an important agricultural emergency. The virus presents a significant ongoing threat to the Canadian swine industry. Developing an understanding of the important epidemiological characteristics and disease transmission dynamics of a novel pathogen such as PEDV is critical for helping to guide the implementation of effective, efficient, and economically feasible disease control and prevention strategies that are able to help decrease the impact of an outbreak.",2017 Jan 5,"['Greer, Amy L.', 'Spence, Kelsey', 'Gardner, Emma']",BMC Vet Res,,,True
4e45854eace4e5bb9255ad31f7425545f931f3fe,PMC,Pseudorabies virus infection (Aujeszky’s disease) in an Iberian lynx (Lynx pardinus) in Spain: a case report,http://dx.doi.org/10.1186/s12917-016-0938-7,PMC5217549,28056966,CC BY,"BACKGROUND: The only natural hosts of Pseudorabies virus (PRV) are members of the family Suidae (Sus scrofa scrofa). In species other than suids infection is normally fatal. In these mammals, including carnivores, PRV typically causes serious neurologic disease. The endangered Iberian lynx (Lynx pardinus) is a wild feline endemic to south-western Europe (Iberian Peninsula). The Iberian lynx was found to be the world’s most endangered felid species in 2002. In wild felines, PRV infection has only been previously reported once in a Florida panther in 1994. No seropositive lynxes have ever been found, nor has PRV been detected in dead Iberian lynxes to date. CASE PRESENTATION: We describe the first reported case of pseudorabies in an Iberian lynx (Lynx pardinus). Pseudorabies was diagnosed in a young wild Iberian lynx from Extremadura (SW Spain) by histopathological examination, immunohistochemistry, polymerase chain reaction (PCR) and sequence analysis. Gross lesions included alopecia of the ventral neck, bloody gastro-intestinal contents and congestion of the brain. Histopathological analysis showed a moderate nonsuppurative meningoencephalitis with diffuse areas of demyelination, necrotizing gastritis and enteritis of the small intestine. Pseudorabies virus (PRV) antigen was found in neuronal and non-neuronal cells of the brain, tonsils, and gastric glandular epithelial cells by immunohistochemical analysis. The presence of the virus in the brain was confirmed by nested PCR. The sequence analysis of the 146 bp fragment (from the viral glycoprotein B gene) showed that the amplified sequence matched (with 100% identity) the PRV genome. Furthermore, specific DNA from glycoprotein D and E encoding-genes was detected by conventional and real-time PCR, respectively, confirming the latter that this infection was produced by a wild-type PRV strain. CONCLUSIONS: This study supports the suspicion that PRV could infect the Iberian lynx. The detection of PRV in a dead Iberian lynx suggests that the virus may have a negative impact on the survival of endangered lynxes in the wild. However, because this is the first verified instance of lynx mortality resulting from pseudorabies, its true impact on the population is unknown. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0938-7) contains supplementary material, which is available to authorized users.",2017 Jan 5,"['Masot, A. Javier', 'Gil, María', 'Risco, David', 'Jiménez, Olga M.', 'Núñez, José I.', 'Redondo, Eloy']",BMC Vet Res,,,True
6aea4f0b8aaacfac3d0d3b49bd7558481da9b03f,PMC,One-Pot Reverse Transcriptional Loop-Mediated Isothermal Amplification (RT-LAMP) for Detecting MERS-CoV,http://dx.doi.org/10.3389/fmicb.2016.02166,PMC5220095,28119682,CC BY,"Due to the limitation of rapid development of specific antiviral drug or vaccine for novel emerging viruses, an accurate and rapid diagnosis is a key to manage the virus spread. We developed an efficient and rapid method with high specificity for the Middle East Respiratory Syndrome coronavirus (MERS-CoV), based on one-pot reverse transcription loop-mediated isothermal amplification (one-pot RT-LAMP). A set of six LAMP primers [F3, B3, FIP, BIP, LF (Loop-F), and LB (Loop-B)] were designed using the sequence of nucleocapsid (N) gene with optimized RT-LAMP enzyme conditions: 100 U M-MLV RTase and 4 U Bst polymerase, implying that the reaction was able to detect four infectious viral genome copies of MERS-CoV within a 60 min reaction time period. Significantly, EvaGreen dye has better signal read-out properties in one-pot RT-LAMP reaction and is more compatible with DNA polymerase than SYBR green I. Isothermally amplified specific N genes were further evaluated using field-deployable microchamber devices, leading to the specific identification of as few as 0.4 infectious viral genome copies, with no cross-reaction to the other acute respiratory disease viruses, including influenza type A (H1N1 and H3N2), type B, human coronavirus 229E, and human metapneumovirus. This sensitive, specific and feasible method provides a large-scale technical support in emergencies, and is also applied as a sample-to-detection module in Point of Care Testing devices.",2017 Jan 9,"['Lee, Se Hee', 'Baek, Yun Hee', 'Kim, Yang-Hoon', 'Choi, Young-Ki', 'Song, Min-Suk', 'Ahn, Ji-Young']",Front Microbiol,,,True
f7f482ba4aaa3ef0d620d9aad8c9635f88806d8e,PMC,The autophagy elongation complex (ATG5-12/16L1) positively regulates HCV replication and is required for wild-type membranous web formation,http://dx.doi.org/10.1038/srep40351,PMC5220323,28067309,CC BY,"Hepatitis C virus (HCV) infection induces intracellular membrane rearrangements, thus forming a membranous web (MW) in which HCV replication and assembly occur. The HCV-induced MW is primarily composed of double membrane vesicles (DMVs) transfused by multi-membrane vesicles. The autophagy machinery has been proposed to participate in the formation of such vesicles. However, no clear evidence has been found linking autophagy to the formation of these DMVs. In this study, we evaluated the role of the autophagy elongation complex (ATG5-12/16L1) in HCV replication and MW formation. Using a dominant negative form of ATG12 and an siRNA approach, we demonstrated that the ATG5-12 conjugate, but not LC3-II formation, is crucial for efficient viral replication. Furthermore, purification of HCV MW revealed the presence of ATG5-12 and ATG16L1 along with HCV nonstructural proteins. Interestingly, LC3 was not recruited along with the elongation complex to the site of viral replication. Finally, inhibition of the elongation complex, but not LC3, greatly impaired the formation of the wild-type MW phenotype. To our knowledge, this study provides the first evidence of the involvement of autophagy proteins in the formation of wild-type MWs.",2017 Jan 9,"['Fahmy, Ahmed M.', 'Labonté, Patrick']",Sci Rep,,,True
f130e5346baa10d030f853af0b490818527a2508,PMC,The autophagy elongation complex (ATG5-12/16L1) positively regulates HCV replication and is required for wild-type membranous web formation,http://dx.doi.org/10.1038/srep40351,PMC5220323,28067309,CC BY,"Hepatitis C virus (HCV) infection induces intracellular membrane rearrangements, thus forming a membranous web (MW) in which HCV replication and assembly occur. The HCV-induced MW is primarily composed of double membrane vesicles (DMVs) transfused by multi-membrane vesicles. The autophagy machinery has been proposed to participate in the formation of such vesicles. However, no clear evidence has been found linking autophagy to the formation of these DMVs. In this study, we evaluated the role of the autophagy elongation complex (ATG5-12/16L1) in HCV replication and MW formation. Using a dominant negative form of ATG12 and an siRNA approach, we demonstrated that the ATG5-12 conjugate, but not LC3-II formation, is crucial for efficient viral replication. Furthermore, purification of HCV MW revealed the presence of ATG5-12 and ATG16L1 along with HCV nonstructural proteins. Interestingly, LC3 was not recruited along with the elongation complex to the site of viral replication. Finally, inhibition of the elongation complex, but not LC3, greatly impaired the formation of the wild-type MW phenotype. To our knowledge, this study provides the first evidence of the involvement of autophagy proteins in the formation of wild-type MWs.",2017 Jan 9,"['Fahmy, Ahmed M.', 'Labonté, Patrick']",Sci Rep,,,False
80514d274dfaa180080c8eb0bb261c0af5c95c49,PMC,Development of a Recombinase Polymerase Amplification Assay for Detection of Epidemic Human Noroviruses,http://dx.doi.org/10.1038/srep40244,PMC5220337,28067278,CC BY,"Human norovirus is a leading cause of viral gastroenteritis worldwide. Rapid detection could facilitate control, however widespread point-of-care testing is infrequently done due to the lack of robust and portable methods. Recombinase polymerase amplification (RPA) is a novel isothermal method which rapidly amplifies and detects nucleic acids using a simple device in near real-time. An RT-RPA assay targeting a recent epidemic human norovirus strain (GII.4 New Orleans) was developed and evaluated in this study. The assay successfully detected purified norovirus RNA from multiple patient outbreak isolates and had a limit of detection of 3.40 ± 0.20 log(10) genomic copies (LGC), which is comparable to most other reported isothermal norovirus amplification methods. The assay also detected norovirus in directly boiled stool, and displayed better resistance to inhibitors than a commonly used RT-qPCR assay. The assay was specific, as it did not amplify genomes from 9 non-related enteric viruses and bacteria. The assay detected norovirus in some samples in as little as 6 min, and the entire detection process can be performed in less than 30 min. The reported RT-RPA method shows promise for sensitive point-of-care detection of epidemic human norovirus, and is the fastest human norovirus amplification method to date.",2017 Jan 9,"['Moore, Matthew D.', 'Jaykus, Lee-Ann']",Sci Rep,,,True
50df576e673f129424832b55011ea30334063e47,PMC,Development of a Recombinase Polymerase Amplification Assay for Detection of Epidemic Human Noroviruses,http://dx.doi.org/10.1038/srep40244,PMC5220337,28067278,CC BY,"Human norovirus is a leading cause of viral gastroenteritis worldwide. Rapid detection could facilitate control, however widespread point-of-care testing is infrequently done due to the lack of robust and portable methods. Recombinase polymerase amplification (RPA) is a novel isothermal method which rapidly amplifies and detects nucleic acids using a simple device in near real-time. An RT-RPA assay targeting a recent epidemic human norovirus strain (GII.4 New Orleans) was developed and evaluated in this study. The assay successfully detected purified norovirus RNA from multiple patient outbreak isolates and had a limit of detection of 3.40 ± 0.20 log(10) genomic copies (LGC), which is comparable to most other reported isothermal norovirus amplification methods. The assay also detected norovirus in directly boiled stool, and displayed better resistance to inhibitors than a commonly used RT-qPCR assay. The assay was specific, as it did not amplify genomes from 9 non-related enteric viruses and bacteria. The assay detected norovirus in some samples in as little as 6 min, and the entire detection process can be performed in less than 30 min. The reported RT-RPA method shows promise for sensitive point-of-care detection of epidemic human norovirus, and is the fastest human norovirus amplification method to date.",2017 Jan 9,"['Moore, Matthew D.', 'Jaykus, Lee-Ann']",Sci Rep,,,False
3eb1bcee33c1121bd5307cf9a0c91f2510f4f79f,PMC,Comparative interactomics for virus–human protein–protein interactions: DNA viruses versus RNA viruses,http://dx.doi.org/10.1002/2211-5463.12167,PMC5221455,28097092,CC BY,"Viruses are obligatory intracellular pathogens and completely depend on their hosts for survival and reproduction. The strategies adopted by viruses to exploit host cell processes and to evade host immune systems during infections may differ largely with the type of the viral genetic material. An improved understanding of these viral infection mechanisms is only possible through a better understanding of the pathogen–host interactions (PHIs) that enable viruses to enter into the host cells and manipulate the cellular mechanisms to their own advantage. Experimentally‐verified protein–protein interaction (PPI) data of pathogen–host systems only became available at large scale within the last decade. In this study, we comparatively analyzed the current PHI networks belonging to DNA and RNA viruses and their human host, to get insights into the infection strategies used by these viral groups. We investigated the functional properties of human proteins in the PHI networks, to observe and compare the attack strategies of DNA and RNA viruses. We observed that DNA viruses are able to attack both human cellular and metabolic processes simultaneously during infections. On the other hand, RNA viruses preferentially interact with human proteins functioning in specific cellular processes as well as in intracellular transport and localization within the cell. Observing virus‐targeted human proteins, we propose heterogeneous nuclear ribonucleoproteins and transporter proteins as potential antiviral therapeutic targets. The observed common and specific infection mechanisms in terms of viral strategies to attack human proteins may provide crucial information for further design of broad and specific next‐generation antiviral therapeutics.",2017 Jan 4,"['Durmuş, Saliha', 'Ülgen, Kutlu Ö.']",FEBS Open Bio,,,True
6f0c490d80ef3e7032010a057baa96d4d45ababc,PMC,Behavioural change models for infectious disease transmission: a systematic review (2010–2015),http://dx.doi.org/10.1098/rsif.2016.0820,PMC5221530,28003528,CC BY,"We review behavioural change models (BCMs) for infectious disease transmission in humans. Following the Cochrane collaboration guidelines and the PRISMA statement, our systematic search and selection yielded 178 papers covering the period 2010–2015. We observe an increasing trend in published BCMs, frequently coupled to (re)emergence events, and propose a categorization by distinguishing how information translates into preventive actions. Behaviour is usually captured by introducing information as a dynamic parameter (76/178) or by introducing an economic objective function, either with (26/178) or without (37/178) imitation. Approaches using information thresholds (29/178) and exogenous behaviour formation (16/178) are also popular. We further classify according to disease, prevention measure, transmission model (with 81/178 population, 6/178 metapopulation and 91/178 individual-level models) and the way prevention impacts transmission. We highlight the minority (15%) of studies that use any real-life data for parametrization or validation and note that BCMs increasingly use social media data and generally incorporate multiple sources of information (16/178), multiple types of information (17/178) or both (9/178). We conclude that individual-level models are increasingly used and useful to model behaviour changes. Despite recent advancements, we remain concerned that most models are purely theoretical and lack representative data and a validation process.",2016 Dec,"['Verelst, Frederik', 'Willem, Lander', 'Beutels, Philippe']",J R Soc Interface,,,True
b8a1d1bdea4cc683b11719ab5e20e2b85f7cb08e,PMC,Enteric Pathogens and Coinfections in Foals with and without Diarrhea,http://dx.doi.org/10.1155/2016/1512690,PMC5223019,28116290,CC BY,"Diarrhea is a major clinical problem affecting foals up to 3 months of age. The aim of this study was to identify enteric microorganisms involved in monoinfections and coinfections and the associated virulence factors in healthy and diarrheic foals. Diarrheic (D) (n = 56) and nondiarrheic (ND) foals (n = 60) up to three months of age were studied. Fecal samples were analyzed for identification of infectious agents (microbiological culturing, molecular techniques, and microscopic analyses). Escherichia coli fimH (30% versus 25%), Salmonella spp. (25% versus 7%), Strongyloides westeri (25% versus 25%), Clostridium perfringens type A (21% versus 10%), E. coli ag43 (20% versus 35%), Strongylus (11% versus 18%), and vapA-positive Rhodococcus equi (5% versus 2%) were the most frequent enteric pathogens detected in D and ND foals, respectively. The frequency of toxin A-positive C. perfringens was significantly increased in the D (p = 0.033) compared with the ND animals. R. equi strains harboring virulent plasmids were also identified (VapA 85-kb type I and VapA 87-kb type I) in D and ND foals. Coinfections were observed in 46% of the D and 33% of the ND foals. Our results demonstrate the great diversity of enteric pathogens, virulence factors, and coinfections involved in enteric infections of foals.",2016 Dec 27,"['Olivo, Giovane', 'Lucas, Thays Mizuki', 'Borges, Alexandre Secorun', 'Silva, Rodrigo Otávio Silveira', 'Lobato, Francisco Carlos Faria', 'Siqueira, Amanda Keller', 'da Silva Leite, Domingos', 'Brandão, Paulo Eduardo', 'Gregori, Fábio', 'de Oliveira-Filho, José Paes', 'Takai, Shinji', 'Ribeiro, Márcio Garcia']",Biomed Res Int,,,True
e0359b1b4c6d229299cb7b9f149bc9b943a2077f,PMC,Sporadic cases of adult measles: a research article,http://dx.doi.org/10.1186/s13104-017-2374-6,PMC5223409,28069071,CC BY,"BACKGROUND: Measles caused by a paramyxovirus, characterized by fever, malaise, cough, coryza conjunctivitis, a maculopapular rash is known to result in pneumonia, encephalitis and death. Fatal cases of measles in Sri Lanka are rare after implementation of the National Immunization Programme in 1984. Thereafter 0.1% case fatality rate was observed during October 1999–June 2000 which is a very low figure compared to other regional countries. Immunization guidelines were further revised in 2001, 2011 and in 2012 when additional immunization was recommended to age group 4–21 years; who are likely to have inadequate immunization, in order to achieve elimination of Measles by 2020. However, in 2013–2014, 4690 cases were reported and the majority were children less than 1 year of age. The occurrence in adults is hard to retrieve in published epidemiological reports, however had been 38% (out of 1008 patients) in the 3rd quarter of 2013. During this outbreak 73/101 (72%) reported from the North Central Province of Sri Lanka had been more than 12 years of age with 50% being more than 29 years. 14 Sri lankan adult patients [median age 32 years (range 25–48)] who presented sporadically from June 2014 to March 2016, with confirmed measles infection were enrolled retrospectively after informed consent. Details with regards to their clinical presentation, immunization and other relevant areas were collected using an interviewer administered questionnaire or using patient management records. RESULTS: The patients presented with high fever, headache, severe body aches, sore throat, dry cough, intense tearing, red eyes and posterior cervical lymphadenopathy over 3–5 days duration. Later they developed discrete maculopapular rash helping the diagnosis. They had a variable degree of leucopenia, lymphocytosis, thrombocytopenia and derangements in the liver functions mimicking any other acute febrile illnesses such as dengue, chikungunya, leptospirosis or Zika virus infection. CONCLUSION: At least a 3–5 day delay in the diagnosis was observed (even after the appearance of the rash in some patients), due to non-awareness of its occurrence, unfamiliarity of measles in adults, non-specific nature of the illness and non-availability of rapid diagnostics, risking transmission to the immune-compromised or non-immune staff or patients. Identification of the source of infection in these sporadic adult cases and their virologic surveillance and molecular epidemiology will be important to interrupt the transmission and to achieve the targeted elimination of measles from Sri Lanka by 2020.",2017 Jan 10,"['Premaratna, Ranjan', 'Luke, Nathasha', 'Perera, Harsha', 'Gunathilake, Mahesh', 'Amarasena, Pubudu', 'Chandrasena, T. G. A. Nilmini']",BMC Res Notes,,,True
7cd8d3fec1f3a8251b75a50aad856e1b5526de83,PMC,Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations,http://dx.doi.org/10.1186/s13756-016-0149-9,PMC5223492,28078082,CC BY,"Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13756-016-0149-9) contains supplementary material, which is available to authorized users.",2017 Jan 10,"['Storr, Julie', 'Twyman, Anthony', 'Zingg, Walter', 'Damani, Nizam', 'Kilpatrick, Claire', 'Reilly, Jacqui', 'Price, Lesley', 'Egger, Matthias', 'Grayson, M. Lindsay', 'Kelley, Edward', 'Allegranzi, Benedetta', None]",Antimicrob Resist Infect Control,,,True
c14ce2c27ca770924c1ca4a4fef0fa5b532f73c1,PMC,Cluster randomised controlled trial to examine medical mask use as source control for people with respiratory illness,http://dx.doi.org/10.1136/bmjopen-2016-012330,PMC5223715,28039289,CC BY,"RATIONALE: Medical masks are commonly used by sick individuals with influenza-like illness (ILI) to prevent spread of infections to others, but clinical efficacy data are absent. OBJECTIVE: Determine whether medical mask use by sick individuals with ILI protects well contacts from related respiratory infections. SETTING: 6 major hospitals in 2 districts of Beijing, China. DESIGN: Cluster randomised controlled trial. PARTICIPANTS: 245 index cases with ILI. INTERVENTION: Index cases with ILI were randomly allocated to medical mask (n=123) and control arms (n=122). Since 43 index cases in the control arm also used a mask during the study period, an as-treated post hoc analysis was performed by comparing outcomes among household members of index cases who used a mask (mask group) with household members of index cases who did not use a mask (no-mask group). MAIN OUTCOME MEASURE: Primary outcomes measured in household members were clinical respiratory illness, ILI and laboratory-confirmed viral respiratory infection. RESULTS: In an intention-to-treat analysis, rates of clinical respiratory illness (relative risk (RR) 0.61, 95% CI 0.18 to 2.13), ILI (RR 0.32, 95% CI 0.03 to 3.13) and laboratory-confirmed viral infections (RR 0.97, 95% CI 0.06 to 15.54) were consistently lower in the mask arm compared with control, although not statistically significant. A post hoc comparison between the mask versus no-mask groups showed a protective effect against clinical respiratory illness, but not against ILI and laboratory-confirmed viral respiratory infections. CONCLUSIONS: The study indicates a potential benefit of medical masks for source control, but is limited by small sample size and low secondary attack rates. Larger trials are needed to confirm efficacy of medical masks as source control. TRIAL REGISTRATION NUMBER: ACTRN12613000852752; Results.",2016 Dec 30,"['MacIntyre, Chandini Raina', 'Zhang, Yi', 'Chughtai, Abrar Ahmad', 'Seale, Holly', 'Zhang, Daitao', 'Chu, Yanhui', 'Zhang, Haiyan', 'Rahman, Bayzidur', 'Wang, Quanyi']",BMJ Open,,,True
6fa9d1fe1938a48f36f837cec479925de3a69b64,PMC,IL-1β is a key cytokine that induces trypsin upregulation in the influenza virus–cytokine–trypsin cycle,http://dx.doi.org/10.1007/s00705-016-3093-3,PMC5225228,27714503,CC BY,"Severe influenza is characterized by a cytokine storm, and the influenza virus–cytokine–trypsin cycle is one of the important mechanisms of viral multiplication and multiple organ failure. The aim of this study was to define the key cytokine(s) responsible for trypsin upregulation. Mice were infected with influenza virus strain A/Puerto Rico/8/34 (H1N1) or treated individually or with a combination of interleukin-1β, interleukin-6, and tumor necrosis factor α. The levels of these cytokines and trypsin in the lungs were monitored. The neutralizing effects of anti-IL-1β antibodies on cytokine and trypsin expression in human A549 cells and lung inflammation in the infected mice were examined. Infection induced interleukin-1β, interleukin-6, tumor necrosis factor α, and ectopic trypsin in mouse lungs in a dose- and time-dependent manner. Intraperitoneal administration of interleukin-1β combined with other cytokines tended to upregulate trypsin and cytokine expression in the lungs, but the combination without interleukin-1β did not induce trypsin. In contrast, incubation of A549 cells with interleukin-1β alone induced both cytokines and trypsin, and anti-interleukin-1β antibody treatment abrogated these effects. Administration of the antibody in the infected mice reduced lung inflammation area. These findings suggest that IL-1β plays a key role in trypsin upregulation and has a pathological role in multiple organ failure.",2017 Oct 6,"['Indalao, I. L.', 'Sawabuchi, T.', 'Takahashi, E.', 'Kido, H.']",Arch Virol,,,True
64536ef4a2d1df35305df73397d745ae55be8d47,PMC,Single- and multiple viral respiratory infections in children: disease and management cannot be related to a specific pathogen,http://dx.doi.org/10.1186/s12879-016-2118-6,PMC5225597,28077074,CC BY,"BACKGROUND: The number of viral pathogens associated with pediatric acute respiratory tract infection (ARI) has grown since the introduction of reverse transcription real-time polymerase chain reaction (RT-PCR) assays. Multiple viruses are detected during a single ARI episode in approximately a quarter of all cases. The clinical relevance of these multiple detections is unclear, as is the role of the individual virus. We therefore investigated the correlation between clinical data and RT-PCR results in children with single- and multiple viral ARI. METHODS: Data from children with ARI were prospectively collected during two winter seasons. RT-PCR testing for 15 viruses was performed in 560 ARI episodes. In the patients with a single-viral etiology, clinical data, laboratory findings, patient management- and outcome data were compared between the different viruses. With this information, we compared data from children of whom RT-PCR data were negative, with children with single- and multiple viral positive results. RESULTS: The viral detection rate was 457/560 (81.6%) of which 331/560 (59.1%) were single infections and 126/560 (22.5%) were multiple infections. In single viral infections, some statistically significant differences in demographics, clinical findings, disease severity and outcome were found between children with different viral etiologies. However, no clinically recognizable pattern was established to be virus-specific. In a multivariate analysis, the only variables that were correlated with longer hospital stay were the use of oxygen and nebulizer therapy, irrespective of the viral pathogen. Children with RT-PCR positive test results had a significant higher disease severity, fever, length of hospital stay, days of extra oxygen supply, and days of antibiotic treatment than children with a negative RT-PCR test result. For children with single- versus children with multiple positive RT-PCR test results, these differences were not significant. CONCLUSIONS: Disease (severity), management and outcome in pediatric ARI are not associated with a specific virus. Single- and multiple viral ARI do not significantly differ with regard to clinical outcome and patient management. For general pediatrics, RT-PCR assays should be restricted to pathogens for which therapy is available or otherwise may have clinical consequences. Further research with an extended panel of RT-PCR assays and a larger number of inclusions is necessary to further validate our findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-2118-6) contains supplementary material, which is available to authorized users.",2017 Jan 11,"['Wishaupt, Jérôme O.', 'van der Ploeg, Tjeerd', 'de Groot, Ronald', 'Versteegh, Florens G. A.', 'Hartwig, Nico G.']",BMC Infect Dis,,,True
b360dd33baf9170084ca4b452e13e92d3bbdefee,PMC,When Viruses Don’t Go Viral: The Importance of Host Phylogeographic Structure in the Spatial Spread of Arenaviruses,http://dx.doi.org/10.1371/journal.ppat.1006073,PMC5226678,28076397,CC BY,"Many emerging infections are RNA virus spillovers from animal reservoirs. Reservoir identification is necessary for predicting the geographic extent of infection risk, but rarely are taxonomic levels below the animal species considered as reservoir, and only key circumstances in nature and methodology allow intrinsic virus-host associations to be distinguished from simple geographic (co-)isolation. We sampled and genetically characterized in detail a contact zone of two subtaxa of the rodent Mastomys natalensis in Tanzania. We find two distinct arenaviruses, Gairo and Morogoro virus, each spatially confined to a single M. natalensis subtaxon, only co-occurring at the contact zone’s centre. Inter-subtaxon hybridization at this centre and a continuum of quality habitat for M. natalensis show that both viruses have the ecological opportunity to spread into the other substaxon’s range, but do not, strongly suggesting host-intrinsic barriers. Such barriers could explain why human cases of another M. natalensis-borne arenavirus, Lassa virus, are limited to West Africa.",2017 Jan 11,"['Gryseels, Sophie', 'Baird, Stuart J. E.', 'Borremans, Benny', 'Makundi, Rhodes', 'Leirs, Herwig', 'Goüy de Bellocq, Joëlle']",PLoS Pathog,,,True
28f3721175c93e3f6ca2eea98d30ac3ea45a5f68,PMC,When Viruses Don’t Go Viral: The Importance of Host Phylogeographic Structure in the Spatial Spread of Arenaviruses,http://dx.doi.org/10.1371/journal.ppat.1006073,PMC5226678,28076397,CC BY,"Many emerging infections are RNA virus spillovers from animal reservoirs. Reservoir identification is necessary for predicting the geographic extent of infection risk, but rarely are taxonomic levels below the animal species considered as reservoir, and only key circumstances in nature and methodology allow intrinsic virus-host associations to be distinguished from simple geographic (co-)isolation. We sampled and genetically characterized in detail a contact zone of two subtaxa of the rodent Mastomys natalensis in Tanzania. We find two distinct arenaviruses, Gairo and Morogoro virus, each spatially confined to a single M. natalensis subtaxon, only co-occurring at the contact zone’s centre. Inter-subtaxon hybridization at this centre and a continuum of quality habitat for M. natalensis show that both viruses have the ecological opportunity to spread into the other substaxon’s range, but do not, strongly suggesting host-intrinsic barriers. Such barriers could explain why human cases of another M. natalensis-borne arenavirus, Lassa virus, are limited to West Africa.",2017 Jan 11,"['Gryseels, Sophie', 'Baird, Stuart J. E.', 'Borremans, Benny', 'Makundi, Rhodes', 'Leirs, Herwig', 'Goüy de Bellocq, Joëlle']",PLoS Pathog,,,False
409834df62ccb98e2497be0afcb86af5b5f815a4,PMC,When Viruses Don’t Go Viral: The Importance of Host Phylogeographic Structure in the Spatial Spread of Arenaviruses,http://dx.doi.org/10.1371/journal.ppat.1006073,PMC5226678,28076397,CC BY,"Many emerging infections are RNA virus spillovers from animal reservoirs. Reservoir identification is necessary for predicting the geographic extent of infection risk, but rarely are taxonomic levels below the animal species considered as reservoir, and only key circumstances in nature and methodology allow intrinsic virus-host associations to be distinguished from simple geographic (co-)isolation. We sampled and genetically characterized in detail a contact zone of two subtaxa of the rodent Mastomys natalensis in Tanzania. We find two distinct arenaviruses, Gairo and Morogoro virus, each spatially confined to a single M. natalensis subtaxon, only co-occurring at the contact zone’s centre. Inter-subtaxon hybridization at this centre and a continuum of quality habitat for M. natalensis show that both viruses have the ecological opportunity to spread into the other substaxon’s range, but do not, strongly suggesting host-intrinsic barriers. Such barriers could explain why human cases of another M. natalensis-borne arenavirus, Lassa virus, are limited to West Africa.",2017 Jan 11,"['Gryseels, Sophie', 'Baird, Stuart J. E.', 'Borremans, Benny', 'Makundi, Rhodes', 'Leirs, Herwig', 'Goüy de Bellocq, Joëlle']",PLoS Pathog,,,False
76dbfa70731b63e370a50910b03e74bfca82eb2d,PMC,When Viruses Don’t Go Viral: The Importance of Host Phylogeographic Structure in the Spatial Spread of Arenaviruses,http://dx.doi.org/10.1371/journal.ppat.1006073,PMC5226678,28076397,CC BY,"Many emerging infections are RNA virus spillovers from animal reservoirs. Reservoir identification is necessary for predicting the geographic extent of infection risk, but rarely are taxonomic levels below the animal species considered as reservoir, and only key circumstances in nature and methodology allow intrinsic virus-host associations to be distinguished from simple geographic (co-)isolation. We sampled and genetically characterized in detail a contact zone of two subtaxa of the rodent Mastomys natalensis in Tanzania. We find two distinct arenaviruses, Gairo and Morogoro virus, each spatially confined to a single M. natalensis subtaxon, only co-occurring at the contact zone’s centre. Inter-subtaxon hybridization at this centre and a continuum of quality habitat for M. natalensis show that both viruses have the ecological opportunity to spread into the other substaxon’s range, but do not, strongly suggesting host-intrinsic barriers. Such barriers could explain why human cases of another M. natalensis-borne arenavirus, Lassa virus, are limited to West Africa.",2017 Jan 11,"['Gryseels, Sophie', 'Baird, Stuart J. E.', 'Borremans, Benny', 'Makundi, Rhodes', 'Leirs, Herwig', 'Goüy de Bellocq, Joëlle']",PLoS Pathog,,,False
5a34dd045c63483689fd09292fc0256f32b137a9,PMC,When Viruses Don’t Go Viral: The Importance of Host Phylogeographic Structure in the Spatial Spread of Arenaviruses,http://dx.doi.org/10.1371/journal.ppat.1006073,PMC5226678,28076397,CC BY,"Many emerging infections are RNA virus spillovers from animal reservoirs. Reservoir identification is necessary for predicting the geographic extent of infection risk, but rarely are taxonomic levels below the animal species considered as reservoir, and only key circumstances in nature and methodology allow intrinsic virus-host associations to be distinguished from simple geographic (co-)isolation. We sampled and genetically characterized in detail a contact zone of two subtaxa of the rodent Mastomys natalensis in Tanzania. We find two distinct arenaviruses, Gairo and Morogoro virus, each spatially confined to a single M. natalensis subtaxon, only co-occurring at the contact zone’s centre. Inter-subtaxon hybridization at this centre and a continuum of quality habitat for M. natalensis show that both viruses have the ecological opportunity to spread into the other substaxon’s range, but do not, strongly suggesting host-intrinsic barriers. Such barriers could explain why human cases of another M. natalensis-borne arenavirus, Lassa virus, are limited to West Africa.",2017 Jan 11,"['Gryseels, Sophie', 'Baird, Stuart J. E.', 'Borremans, Benny', 'Makundi, Rhodes', 'Leirs, Herwig', 'Goüy de Bellocq, Joëlle']",PLoS Pathog,,,False
0072159e1ebecc889e9bcabb58bb45c47e18a403,PMC,Chaperone-Mediated Autophagy Protein BAG3 Negatively Regulates Ebola and Marburg VP40-Mediated Egress,http://dx.doi.org/10.1371/journal.ppat.1006132,PMC5226679,28076420,CC BY,"Ebola (EBOV) and Marburg (MARV) viruses are members of the Filoviridae family which cause outbreaks of hemorrhagic fever. The filovirus VP40 matrix protein is essential for virus assembly and budding, and its PPxY L-domain motif interacts with WW-domains of specific host proteins, such as Nedd4 and ITCH, to facilitate the late stage of virus-cell separation. To identify additional WW-domain-bearing host proteins that interact with VP40, we used an EBOV PPxY-containing peptide to screen an array of 115 mammalian WW-domain-bearing proteins. Using this unbiased approach, we identified BCL2 Associated Athanogene 3 (BAG3), a member of the BAG family of molecular chaperone proteins, as a specific VP40 PPxY interactor. Here, we demonstrate that the WW-domain of BAG3 interacts with the PPxY motif of both EBOV and MARV VP40 and, unexpectedly, inhibits budding of both eVP40 and mVP40 virus-like particles (VLPs), as well as infectious VSV-EBOV recombinants. BAG3 is a stress induced protein that regulates cellular protein homeostasis and cell survival through chaperone-mediated autophagy (CMA). Interestingly, our results show that BAG3 alters the intracellular localization of VP40 by sequestering VP40 away from the plasma membrane. As BAG3 is the first WW-domain interactor identified that negatively regulates budding of VP40 VLPs and infectious virus, we propose that the chaperone-mediated autophagy function of BAG3 represents a specific host defense strategy to counteract the function of VP40 in promoting efficient egress and spread of virus particles.",2017 Jan 11,"['Liang, Jingjing', 'Sagum, Cari A.', 'Bedford, Mark T.', 'Sidhu, Sachdev S.', 'Sudol, Marius', 'Han, Ziying', 'Harty, Ronald N.']",PLoS Pathog,,,True
05aeae1608e74b17f7c92bc7661e98742e0b3fb6,PMC,X-ray Structure and Enzymatic Activity Profile of a Core Papain-like Protease of MERS Coronavirus with utility for structure-based drug design,http://dx.doi.org/10.1038/srep40292,PMC5228125,28079137,CC BY,"Ubiquitin-like domain 2 (Ubl2) is immediately adjacent to the N-terminus of the papain-like protease (PLpro) domain in coronavirus polyproteins, and it may play a critical role in protease regulation and stability as well as in viral infection. However, our recent cellular studies reveal that removing the Ubl2 domain from MERS PLpro has no effect on its ability to process the viral polyprotein or act as an interferon antagonist, which involves deubiquitinating and deISGylating cellular proteins. Here, we test the hypothesis that the Ubl2 domain is not required for the catalytic function of MERS PLpro in vitro. The X-ray structure of MERS PLpro-∆Ubl2 was determined to 1.9 Å and compared to PLpro containing the N-terminal Ubl2 domain. While the structures were nearly identical, the PLpro-∆Ubl2 enzyme revealed the intact structure of the substrate-binding loop. Moreover, PLpro-∆Ubl2 catalysis against different substrates and a purported inhibitor revealed no differences in catalytic efficiency, substrate specificity, and inhibition. Further, no changes in thermal stability were observed between enzymes. We conclude that the catalytic core of MERS PLpro, i.e. without the Ubl2 domain, is sufficient for catalysis and stability in vitro with utility to evaluate potential inhibitors as a platform for structure-based drug design.",2017 Jan 12,"['Clasman, Jozlyn R.', 'Báez-Santos, Yahira M.', 'Mettelman, Robert C.', 'O’Brien, Amornrat', 'Baker, Susan C.', 'Mesecar, Andrew D.']",Sci Rep,,,True
68a3d9fc9d3f0ea1d8681c2f2e24d793f6e7600c,PMC,X-ray Structure and Enzymatic Activity Profile of a Core Papain-like Protease of MERS Coronavirus with utility for structure-based drug design,http://dx.doi.org/10.1038/srep40292,PMC5228125,28079137,CC BY,"Ubiquitin-like domain 2 (Ubl2) is immediately adjacent to the N-terminus of the papain-like protease (PLpro) domain in coronavirus polyproteins, and it may play a critical role in protease regulation and stability as well as in viral infection. However, our recent cellular studies reveal that removing the Ubl2 domain from MERS PLpro has no effect on its ability to process the viral polyprotein or act as an interferon antagonist, which involves deubiquitinating and deISGylating cellular proteins. Here, we test the hypothesis that the Ubl2 domain is not required for the catalytic function of MERS PLpro in vitro. The X-ray structure of MERS PLpro-∆Ubl2 was determined to 1.9 Å and compared to PLpro containing the N-terminal Ubl2 domain. While the structures were nearly identical, the PLpro-∆Ubl2 enzyme revealed the intact structure of the substrate-binding loop. Moreover, PLpro-∆Ubl2 catalysis against different substrates and a purported inhibitor revealed no differences in catalytic efficiency, substrate specificity, and inhibition. Further, no changes in thermal stability were observed between enzymes. We conclude that the catalytic core of MERS PLpro, i.e. without the Ubl2 domain, is sufficient for catalysis and stability in vitro with utility to evaluate potential inhibitors as a platform for structure-based drug design.",2017 Jan 12,"['Clasman, Jozlyn R.', 'Báez-Santos, Yahira M.', 'Mettelman, Robert C.', 'O’Brien, Amornrat', 'Baker, Susan C.', 'Mesecar, Andrew D.']",Sci Rep,,,False
ebbaea6d90c8fe4ccbb6e65a842689b104acba90,PMC,The Important Role of Lipid Raft-Mediated Attachment in the Infection of Cultured Cells by Coronavirus Infectious Bronchitis Virus Beaudette Strain,http://dx.doi.org/10.1371/journal.pone.0170123,PMC5231368,28081264,CC BY,"Lipid raft is an important element for the cellular entry of some viruses, including coronavirus infectious bronchitis virus (IBV). However, the exact role of lipid rafts in the cellular membrane during the entry of IBV into host cells is still unknown. In this study, we biochemically fractionated IBV-infected cells via sucrose density gradient centrifugation after depleting plasma membrane cholesterol with methyl-β-cyclodextrin or Mevastatin. Our results demonstrated that unlike IBV non-structural proteins, IBV structural proteins co-localized with lipid raft marker caveolin-1. Infectivity assay results of Vero cells illustrated that the drug-induced disruption of lipid rafts significantly suppressed IBV infection. Further studies revealed that lipid rafts were not required for IBV genome replication or virion release at later stages. However, the drug-mediated depletion of lipid rafts in Vero cells before IBV attachment significantly reduced the expression of viral structural proteins, suggesting that drug treatment impaired the attachment of IBV to the cell surface. Our results indicated that lipid rafts serve as attachment factors during the early stages of IBV infection, especially during the attachment stage.",2017 Jan 12,"['Guo, Huichen', 'Huang, Mei', 'Yuan, Quan', 'Wei, Yanquan', 'Gao, Yuan', 'Mao, Lejiao', 'Gu, Lingjun', 'Tan, Yong Wah', 'Zhong, Yanxin', 'Liu, Dingxiang', 'Sun, Shiqi']",PLoS One,,,True
2822c9550311df8e6325df17b17cfde48c9ab6ab,PMC,Quantitative Fluorescence Quenching on Antibody-conjugated Graphene Oxide as a Platform for Protein Sensing,http://dx.doi.org/10.1038/srep40772,PMC5233999,28084438,CC BY,"We created an immunosensing platform for the detection of proteins in a buffer solution. Our sensing platform relies on graphene oxide (GO) nanosheets conjugated with antibodies to provide quantitative binding sites for analyte proteins. When analyte proteins and standard fluorescein-labelled proteins are competing for the binding sites, the assay exhibits quantitative fluorescence quenching by GO for the fluorescein-labelled proteins as determined by the analyte protein concentration. Because of this mechanism, measured fluorescence intensity from unquenched fluorescein-labelled protein was shown to increase with an increasing analyte protein concentration. As an alternative to the conventional enzyme-linked immunosorbent assay (ELISA), our method does not require an enzyme-linked second antibody for protein recognition and the enzyme for optical signal measurement. Thus, it is beneficial with its low cost and fewer systematic errors caused by the series of antigen-antibody recognition steps in ELISA. Immune globulin G (IgG) was introduced as a model protein to test our method and our results showed that the limit of detection for IgG was 4.67 pmol mL(−1) in the buffer solution. This sensing mechanism could be developed into a promising biosensor for the detection of proteins, which would broaden the spectrum of GO applications in both analytical biochemistry and clinical diagnosis.",2017 Jan 13,"['Huang, Ao', 'Li, Weiwei', 'Shi, Shuo', 'Yao, Tianming']",Sci Rep,,,True
f996c22e999ecc9ff3b5cce74bae47fa8b323f23,PMC,Dengue virus compartmentalization during antibody-enhanced infection,http://dx.doi.org/10.1038/srep40923,PMC5234037,28084461,CC BY,"Secondary infection with a heterologous dengue virus (DENV) serotype increases the risk of severe dengue, through a process termed antibody-dependent enhancement (ADE). During ADE, DENV is opsonized with non- or sub-neutralizing antibody levels that augment entry into monocytes and dendritic cells through Fc-gamma receptors (FcγRs). We previously reported that co-ligation of leukocyte immunoglobulin-like receptor-B1 (LILRB1) by antibody-opsonized DENV led to recruitment of SH2 domain-containing phosphatase-1 (SHP-1) to dephosphorylate spleen tyrosine kinase (Syk) and reduce interferon stimulated gene induction. Here, we show that LILRB1 also signals through SHP-1 to attenuate the otherwise rapid acidification for lysosomal enzyme activation following FcγR-mediated uptake of DENV. Reduced or slower trafficking of antibody-opsonized DENV to lytic phagolysosomal compartments, demonstrates how co-ligation of LILRB1 also permits DENV to overcome a cell-autonomous immune response, enhancing intracellular survival of DENV. Our findings provide insights on how antiviral drugs that modify phagosome acidification should be used for viruses such as DENV.",2017 Jan 13,"['Ong, Eugenia Z.', 'Zhang, Summer L.', 'Tan, Hwee Cheng', 'Gan, Esther S.', 'Chan, Kuan Rong', 'Ooi, Eng Eong']",Sci Rep,,,True
9c2b98b09ca25a3e0cf766fc6164de77c403885f,PMC,Dengue virus compartmentalization during antibody-enhanced infection,http://dx.doi.org/10.1038/srep40923,PMC5234037,28084461,CC BY,"Secondary infection with a heterologous dengue virus (DENV) serotype increases the risk of severe dengue, through a process termed antibody-dependent enhancement (ADE). During ADE, DENV is opsonized with non- or sub-neutralizing antibody levels that augment entry into monocytes and dendritic cells through Fc-gamma receptors (FcγRs). We previously reported that co-ligation of leukocyte immunoglobulin-like receptor-B1 (LILRB1) by antibody-opsonized DENV led to recruitment of SH2 domain-containing phosphatase-1 (SHP-1) to dephosphorylate spleen tyrosine kinase (Syk) and reduce interferon stimulated gene induction. Here, we show that LILRB1 also signals through SHP-1 to attenuate the otherwise rapid acidification for lysosomal enzyme activation following FcγR-mediated uptake of DENV. Reduced or slower trafficking of antibody-opsonized DENV to lytic phagolysosomal compartments, demonstrates how co-ligation of LILRB1 also permits DENV to overcome a cell-autonomous immune response, enhancing intracellular survival of DENV. Our findings provide insights on how antiviral drugs that modify phagosome acidification should be used for viruses such as DENV.",2017 Jan 13,"['Ong, Eugenia Z.', 'Zhang, Summer L.', 'Tan, Hwee Cheng', 'Gan, Esther S.', 'Chan, Kuan Rong', 'Ooi, Eng Eong']",Sci Rep,,,False
35c05762c68e41518351ac579286703662345575,PMC,Health system resilience: Lebanon and the Syrian refugee crisis,http://dx.doi.org/10.7189/jogh.06.020704,PMC5234495,28154758,CC BY,"BACKGROUND: Between 2011 and 2013, the Lebanese population increased by 30% due to the influx of Syrian refugees. While a sudden increase of such magnitude represents a shock to the health system, threatening the continuity of service delivery and destabilizing governance, it also offers a unique opportunity to study resilience of a health system amidst ongoing crisis. METHODS: We conceptualized resilience as the capacity of a health system to absorb internal or external shocks (for example prevent or contain disease outbreaks and maintain functional health institutions) while sustaining achievements. We explored factors contributing to the resilience of the Lebanese health system, including networking with stakeholders, diversification of the health system, adequate infrastructure and health human resources, a comprehensive communicable disease response and the integration of the refugees within the health system. RESULTS: In studying the case of Lebanon we used input–process–output–outcome approach to assess the resilience of the Lebanese health system. This approach provided us with a holistic view of the health system, as it captured not only the sustained and improved outcomes, but also the inputs and processes leading to them. CONCLUSION: Our study indicates that the Lebanese health system was resilient as its institutions sustained their performance during the crisis and even improved.",,"['Ammar, Walid', 'Kdouh, Ola', 'Hammoud, Rawan', 'Hamadeh, Randa', 'Harb, Hilda', 'Ammar, Zeina', 'Atun, Rifat', 'Christiani, David', 'Zalloua, Pierre A']",J Glob Health.; 6(2):020704,,,True
5feab9a11d87a3bcb88dedd98948063b7d259ae2,PMC,Preparation of MS2 Phage-Like Particles and Their Use As Potential Process Control Viruses for Detection and Quantification of Enteric RNA Viruses in Different Matrices,http://dx.doi.org/10.3389/fmicb.2016.01911,PMC5234545,28133456,CC BY,"The detection and quantification of enteric RNA viruses is based on isolation of viral RNA from the sample followed by quantitative reverse transcription polymerase chain reaction (RT-qPCR). To control the whole process of analysis and in order to guarantee the validity and reliability of results, process control viruses (PCV) are used. The present article describes the process of preparation and use of such PCV– MS2 phage-like particles (MS2 PLP) – in RT-qPCR detection and quantification of enteric RNA viruses. The MS2 PLP were derived from bacteriophage MS2 carrying a unique and specific de novo-constructed RNA target sequence originating from the DNA of two extinct species. The amount of prepared MS2 particles was quantified using four independent methods – UV spectrophotometry, fluorimetry, transmission electron microscopy and a specifically developed duplex RT-qPCR. To evaluate the usefulness of MS2 PLP in routine diagnostics different matrices known to harbor enteric RNA viruses (swab samples, liver tissue, serum, feces, and vegetables) were artificially contaminated with specific amounts of MS2 PLP. The extraction efficiencies were calculated for each individual matrix. The prepared particles fulfill all requirements for PCV – they are very stable, non-infectious, and are genetically distinct from the target RNA viruses. Due to these properties they represent a good morphological and physiochemical model. The use of MS2 PLP as a PCV in detection and quantification of enteric RNA viruses was evaluated in different types of matrices.",2016 Dec 1,"['Mikel, Pavel', 'Vasickova, Petra', 'Tesarik, Radek', 'Malenovska, Hana', 'Kulich, Pavel', 'Vesely, Tomas', 'Kralik, Petr']",Front Microbiol,,,True
ce90f3248a2ef874c0d7cfe5926a3ca6e56a7f83,PMC,Correlation of cytokine level with the severity of severe fever with thrombocytopenia syndrome,http://dx.doi.org/10.1186/s12985-016-0677-1,PMC5237221,28086978,CC BY,"BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) was an emerging hemorrhagic fever that was caused by a tick-borne bunyavirus, SFTSV. Although SFTSV nonstructural protein can inhibit type I interferon (IFN-I) production Ex Vivo and IFN-I played key role in resistance SFTSV infection in animal model, the role of IFN-I in patients is not investigated. METHODS: We have assayed the concentration of IFN-α, a subtype of IFN-I as well as other cytokines in the sera of SFTS patients and the healthy population with CBA (Cytometric bead array) assay. RESULTS: The results showed that IFN-α, tumor necrosis factor (TNF-α), granulocyte colony-stimulating factor (G-CSF), interferon-γ (IFN-γ), macrophage inflammatory protein (MIP-1α), interleukin-6 (IL-6), IL-10, interferon-inducible protein (IP-10), monocyte chemoattractant protein (MCP-1) were significantly higher in SFTS patients than in healthy persons (p < 0.05); the concentrations of IFN-α, IFN-γ, G-CSF, MIP-1α, IL-6, and IP-10 were significant higher in severe SFTS patients than in mild SFTS patients (p < 0.05). CONCLUSION: The concentration of IFN-α as well as other cytokines (IFN-γ, G-CSF, MIP-1α, IL-6, and IP-10) is correlated with the severity of SFTS, suggesting that type I interferon may not be significant in resistance SFTSV infection in humans and it may play an import role in cytokine storm.",2017 Jan 13,"['Liu, Miao-Miao', 'Lei, Xiao-Ying', 'Yu, Hao', 'Zhang, Jian-zhi', 'Yu, Xue-jie']",Virol J,,,True
3f1dd22fd366efca2448379f7becf69de113353a,PMC,"Randomized, double-blind, placebo-controlled clinical trial to assess the safety and effectiveness of a novel dual-action oral topical formulation against upper respiratory infections",http://dx.doi.org/10.1186/s12879-016-2177-8,PMC5237564,28088167,CC BY,"BACKGROUND: Current prevention options for upper respiratory infections (URIs) are not optimal. We conducted a randomized, double-blinded, placebo-controlled pilot clinical trial to evaluate the safety and efficacy of ARMS-I™ (currently marketed as Halo™) in the prevention of URIs. METHODS: ARMS-I is patented novel formulation for the prevention and treatment of influenza, comprising a broad-spectrum antimicrobial agent (cetylpyridinium chloride, CPC) and components (glycerin and xanthan gum) that form a barrier on the host mucosa, thus preventing viral contact and invasion. Healthy adults (18–45 years of age) were randomized into ARMS-I or placebo group (50 subjects each). The drug was sprayed intra-orally (3× daily) for 75 days. The primary objectives were to establish whether ARMS-I decreased the frequency, severity or duration of URIs. Secondary objectives were to evaluate safety, tolerability, rate of virus detection, acceptability and adherence; effect on URI-associated absenteeism and medical visits; and effect of prior influenza vaccination on study outcomes. RESULTS: Of the 94 individuals who completed the study (placebo: n = 44, ARMS-I: n = 50), six presented with confirmed URI (placebo: 4, ARMS-I: 2), representing a 55% relative reduction, albeit this was statistically not significant). Influenza, coronavirus or rhinovirus were detected in three participants; all in the placebo group. Moreover, frequency of post-treatment exit visits was reduced by 55% in ARMS-I compared to the placebo group (N = 4 and 2, respectively). Fever was reported only in the placebo group. ARMS-I significantly reduced the frequency and severity of cough and sore throat, and duration of cough (P ≤ .019 for all comparisons). ARMS-I was safe, well tolerated, had high acceptability and high adherence to medication use. Medical visits occurred only in the placebo group while absenteeism did not differ between the two arms. Prior influenza vaccination had no effect on study outcome. CONCLUSIONS: This randomized proof-of-concept clinical trial demonstrated that ARMS-I tended to provide protection against URIs in the enrolled study participants, while reducing severity and duration of cough and sore throat. A clinical trial with a larger number of study participants is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02644135 (retrospectively registered). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-2177-8) contains supplementary material, which is available to authorized users.",2017 Jan 14,"['Mukherjee, Pranab K.', 'Esper, Frank', 'Buchheit, Ken', 'Arters, Karen', 'Adkins, Ina', 'Ghannoum, Mahmoud A.', 'Salata, Robert A.']",BMC Infect Dis,,,True
859ab03f9d7e647783e8ac0e112b8bf63207693f,PMC,Interactions between cyclodextrins and cellular components: Towards greener medical applications?,http://dx.doi.org/10.3762/bjoc.12.261,PMC5238526,28144335,CC BY,"In the field of host–guest chemistry, some of the most widely used hosts are probably cyclodextrins (CDs). As CDs are able to increase the water solubility of numerous drugs by inclusion into their hydrophobic cavity, they have been widespread used to develop numerous pharmaceutical formulations. Nevertheless, CDs are also able to interact with endogenous substances that originate from an organism, tissue or cell. These interactions can be useful for a vast array of topics including cholesterol manipulation, treatment of Alzheimer’s disease, control of pathogens, etc. In addition, the use of natural CDs offers the great advantage of avoiding or reducing the use of common petroleum-sourced drugs. In this paper, the general features and applications of CDs have been reviewed as well as their interactions with isolated biomolecules leading to the formation of inclusion or exclusion complexes. Finally, some potential medical applications are highlighted throughout several examples.",2016 Dec 7,"Leclercq, Loïc",Beilstein J Org Chem,,,True
24259e03c484aa60752b90e228fe92f90bf2143d,PMC,Undergraduate Global Health Degrees: The Time is Right,http://dx.doi.org/10.4269/ajtmh.16-0835,PMC5239712,27956655,CC BY,,2017 Jan 11,"Brewer, Timothy F.",Am J Trop Med Hyg,,,True
6b18c718ecf5fb496443591ba267b2ccae0c2863,PMC,Virology on the Internet: the time is right for a new journal,http://dx.doi.org/10.1186/1743-422X-1-1,PMC524032,15507150,CC BY,"Virology Journal is an exclusively on-line, Open Access journal devoted to the presentation of high-quality original research concerning human, animal, plant, insect bacterial, and fungal viruses. Virology Journal will establish a strategic alternative to the traditional virology communication process.",2004 Aug 26,"Garry, Robert F",Virol J,,,True
7c58d98057dc1e0a42c7aede5b3a5ac493a4d99e,PMC,Comparison of loop-mediated isothermal amplification assay and smear microscopy with culture for the diagnostic accuracy of tuberculosis,http://dx.doi.org/10.1186/s12879-016-2140-8,PMC5240421,28095790,CC BY,"BACKGROUND: Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the leading causes of death from infectious diseases worldwide. Sputum smear microscopy remains the most widely available pulmonary TB diagnostic tool particularly in resource limited settings. A highly sensitive diagnostic with minimal infrastructure, cost and training is required. Hence, we assessed the diagnostic performance of Loop-mediated isothermal amplification (LAMP) assay in detecting M.tuberculosis infection in sputum sample compared to LED fluorescent smear microscopy and culture. METHOD: A cross-sectional study was conducted at the University of Gondar Hospital from June 01, 2015 to August 30, 2015. Pulmonary TB diagnosis using sputum LED fluorescence smear microscopy, TB-LAMP assay and culture were done. A descriptive analysis was used to determine demographic characteristics of the study participants. Analysis of sensitivity and specificity for smear microscopy and TB-LAMP compared with culture as a reference test was performed. Cohen’s kappa was calculated as a measure of agreement between the tests. RESULTS: A total of 78 pulmonary presumptive TB patients sputum sample were analyzed. The overall sensitivity and specificity of LAMP were 75 and 98%, respectively. Among smear negative sputum samples, 33.3% sensitivity and 100% specificity of LAMP were observed. Smear microscopy showed 78.6% sensitivity and 98% specificity. LAMP and smear in series had sensitivity of 67.8% and specificity of 100%. LAMP and smear in parallel had sensitivity of 85.7% and specificity of 96%. The agreement between LAMP and fluorescent smear microscopy tests was very good (κ = 0.83, P-value ≤0.0001). CONCLUSIONS: TB-LAMP showed similar specificity but a slightly lower sensitivity with LED fluorescence microscopy. The specificity of LAMP and smear microscopy in series was high. The sensitivity of LAMP was insufficient for smear negative sputum samples.",2017 Jan 17,"['Gelaw, Baye', 'Shiferaw, Yitayal', 'Alemayehu, Marta', 'Bashaw, Abate Assefa']",BMC Infect Dis,,,True
cc43e3bf906ec492da56895a85e1a85d87bf59b2,PMC,Expression and bioactivity of human α-fetoprotein in a Bac-to-Bac system,http://dx.doi.org/10.1042/BSR20160161,PMC5240590,27913752,CC BY,"α-fetoprotein (AFP) is an early serum growth factor in foetal embryonic development and hepatic oncogenesis. A growing number of investigations of AFP as a tumour-specific biomarker have concluded that AFP is an important target for cancer treatment. AFP also plays an immunomodulatory role in the treatment of several autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, myasthenia gravis and thyroiditis. In an effort to support biochemical screening and drug design and discovery, we attempted to express and purify human AFP in a Bac-to-Bac system. Two key factors affecting the expression of recombinant human AFP (R-AFP), namely the infectious baculovirus inoculum volume and the culturing time post-infection, were optimized to maximize the yield. We achieved a high yield of approximately 1.5 mg/l of harvested medium with a 72–96 h incubation period after infection and an inoculum volume ratio of 1:100. We also assessed the role of R-AFP in the proliferation of the human liver cancer cell line Bel 7402, and the results indicated that R-AFP promoted the growth of hepatoma cells. We concluded that this method can produce high yields of R-AFP, which can be used for studies related to AFP.",2017 Jan 17,"['Lin, Bo', 'Liu, Kun', 'Wang, Wenting', 'Li, Wei', 'Dong, Xu', 'Chen, Yi', 'Lu, Yan', 'Guo, Junli', 'Zhu, Mingyue', 'Li, Mengsen']",Biosci Rep,,,True
68daf58b8957645121d653fcecec61447d573bb5,PMC,A Likelihood Approach for Real-Time Calibration of Stochastic Compartmental Epidemic Models,http://dx.doi.org/10.1371/journal.pcbi.1005257,PMC5240920,28095403,CC BY,"Stochastic transmission dynamic models are especially useful for studying the early emergence of novel pathogens given the importance of chance events when the number of infectious individuals is small. However, methods for parameter estimation and prediction for these types of stochastic models remain limited. In this manuscript, we describe a calibration and prediction framework for stochastic compartmental transmission models of epidemics. The proposed method, Multiple Shooting for Stochastic systems (MSS), applies a linear noise approximation to describe the size of the fluctuations, and uses each new surveillance observation to update the belief about the true epidemic state. Using simulated outbreaks of a novel viral pathogen, we evaluate the accuracy of MSS for real-time parameter estimation and prediction during epidemics. We assume that weekly counts for the number of new diagnosed cases are available and serve as an imperfect proxy of incidence. We show that MSS produces accurate estimates of key epidemic parameters (i.e. mean duration of infectiousness, R(0), and R(eff)) and can provide an accurate estimate of the unobserved number of infectious individuals during the course of an epidemic. MSS also allows for accurate prediction of the number and timing of future hospitalizations and the overall attack rate. We compare the performance of MSS to three state-of-the-art benchmark methods: 1) a likelihood approximation with an assumption of independent Poisson observations; 2) a particle filtering method; and 3) an ensemble Kalman filter method. We find that MSS significantly outperforms each of these three benchmark methods in the majority of epidemic scenarios tested. In summary, MSS is a promising method that may improve on current approaches for calibration and prediction using stochastic models of epidemics.",2017 Jan 17,"['Zimmer, Christoph', 'Yaesoubi, Reza', 'Cohen, Ted']",PLoS Comput Biol,,,True
8640647aeb5d12e17f9fce436b6548f68c80dba2,PMC,A Likelihood Approach for Real-Time Calibration of Stochastic Compartmental Epidemic Models,http://dx.doi.org/10.1371/journal.pcbi.1005257,PMC5240920,28095403,CC BY,"Stochastic transmission dynamic models are especially useful for studying the early emergence of novel pathogens given the importance of chance events when the number of infectious individuals is small. However, methods for parameter estimation and prediction for these types of stochastic models remain limited. In this manuscript, we describe a calibration and prediction framework for stochastic compartmental transmission models of epidemics. The proposed method, Multiple Shooting for Stochastic systems (MSS), applies a linear noise approximation to describe the size of the fluctuations, and uses each new surveillance observation to update the belief about the true epidemic state. Using simulated outbreaks of a novel viral pathogen, we evaluate the accuracy of MSS for real-time parameter estimation and prediction during epidemics. We assume that weekly counts for the number of new diagnosed cases are available and serve as an imperfect proxy of incidence. We show that MSS produces accurate estimates of key epidemic parameters (i.e. mean duration of infectiousness, R(0), and R(eff)) and can provide an accurate estimate of the unobserved number of infectious individuals during the course of an epidemic. MSS also allows for accurate prediction of the number and timing of future hospitalizations and the overall attack rate. We compare the performance of MSS to three state-of-the-art benchmark methods: 1) a likelihood approximation with an assumption of independent Poisson observations; 2) a particle filtering method; and 3) an ensemble Kalman filter method. We find that MSS significantly outperforms each of these three benchmark methods in the majority of epidemic scenarios tested. In summary, MSS is a promising method that may improve on current approaches for calibration and prediction using stochastic models of epidemics.",2017 Jan 17,"['Zimmer, Christoph', 'Yaesoubi, Reza', 'Cohen, Ted']",PLoS Comput Biol,,,True
4753387619e93bba84ec49e59c52a5c8d32c6392,PMC,Evaluating Hospital-Based Surveillance for Outbreak Detection in Bangladesh: Analysis of Healthcare Utilization Data,http://dx.doi.org/10.1371/journal.pmed.1002218,PMC5240927,28095468,CC0,"BACKGROUND: The International Health Regulations outline core requirements to ensure the detection of public health threats of international concern. Assessing the capacity of surveillance systems to detect these threats is crucial for evaluating a country’s ability to meet these requirements. METHODS AND FINDINGS: We propose a framework to evaluate the sensitivity and representativeness of hospital-based surveillance and apply it to severe neurological infectious diseases and fatal respiratory infectious diseases in Bangladesh. We identified cases in selected communities within surveillance hospital catchment areas using key informant and house-to-house surveys and ascertained where cases had sought care. We estimated the probability of surveillance detecting different sized outbreaks by distance from the surveillance hospital and compared characteristics of cases identified in the community and cases attending surveillance hospitals. We estimated that surveillance detected 26% (95% CI 18%–33%) of severe neurological disease cases and 18% (95% CI 16%–21%) of fatal respiratory disease cases residing at 10 km distance from a surveillance hospital. Detection probabilities decreased markedly with distance. The probability of detecting small outbreaks (three cases) dropped below 50% at distances greater than 26 km for severe neurological disease and at distances greater than 7 km for fatal respiratory disease. Characteristics of cases attending surveillance hospitals were largely representative of all cases; however, neurological disease cases aged <5 y or from the lowest socioeconomic group and fatal respiratory disease cases aged ≥60 y were underrepresented. Our estimates of outbreak detection rely on suspected cases that attend a surveillance hospital receiving laboratory confirmation of disease and being reported to the surveillance system. The extent to which this occurs will depend on disease characteristics (e.g., severity and symptom specificity) and surveillance resources. CONCLUSION: We present a new approach to evaluating the sensitivity and representativeness of hospital-based surveillance, making it possible to predict its ability to detect emerging threats.",2017 Jan 17,"['Nikolay, Birgit', 'Salje, Henrik', 'Sturm-Ramirez, Katharine', 'Azziz-Baumgartner, Eduardo', 'Homaira, Nusrat', 'Ahmed, Makhdum', 'Iuliano, A. Danielle', 'Paul, Repon C.', 'Rahman, Mahmudur', 'Hossain, M. Jahangir', 'Luby, Stephen P.', 'Cauchemez, Simon', 'Gurley, Emily S.']",PLoS Med,,,True
3a71682c5cd98055ca56bceed7bbf409b5d3cafe,PMC,Evaluating Hospital-Based Surveillance for Outbreak Detection in Bangladesh: Analysis of Healthcare Utilization Data,http://dx.doi.org/10.1371/journal.pmed.1002218,PMC5240927,28095468,CC0,"BACKGROUND: The International Health Regulations outline core requirements to ensure the detection of public health threats of international concern. Assessing the capacity of surveillance systems to detect these threats is crucial for evaluating a country’s ability to meet these requirements. METHODS AND FINDINGS: We propose a framework to evaluate the sensitivity and representativeness of hospital-based surveillance and apply it to severe neurological infectious diseases and fatal respiratory infectious diseases in Bangladesh. We identified cases in selected communities within surveillance hospital catchment areas using key informant and house-to-house surveys and ascertained where cases had sought care. We estimated the probability of surveillance detecting different sized outbreaks by distance from the surveillance hospital and compared characteristics of cases identified in the community and cases attending surveillance hospitals. We estimated that surveillance detected 26% (95% CI 18%–33%) of severe neurological disease cases and 18% (95% CI 16%–21%) of fatal respiratory disease cases residing at 10 km distance from a surveillance hospital. Detection probabilities decreased markedly with distance. The probability of detecting small outbreaks (three cases) dropped below 50% at distances greater than 26 km for severe neurological disease and at distances greater than 7 km for fatal respiratory disease. Characteristics of cases attending surveillance hospitals were largely representative of all cases; however, neurological disease cases aged <5 y or from the lowest socioeconomic group and fatal respiratory disease cases aged ≥60 y were underrepresented. Our estimates of outbreak detection rely on suspected cases that attend a surveillance hospital receiving laboratory confirmation of disease and being reported to the surveillance system. The extent to which this occurs will depend on disease characteristics (e.g., severity and symptom specificity) and surveillance resources. CONCLUSION: We present a new approach to evaluating the sensitivity and representativeness of hospital-based surveillance, making it possible to predict its ability to detect emerging threats.",2017 Jan 17,"['Nikolay, Birgit', 'Salje, Henrik', 'Sturm-Ramirez, Katharine', 'Azziz-Baumgartner, Eduardo', 'Homaira, Nusrat', 'Ahmed, Makhdum', 'Iuliano, A. Danielle', 'Paul, Repon C.', 'Rahman, Mahmudur', 'Hossain, M. Jahangir', 'Luby, Stephen P.', 'Cauchemez, Simon', 'Gurley, Emily S.']",PLoS Med,,,False
4b7667a10db8449042b2fa73329cdfac5358ad34,PMC,"Comparing Human Metapneumovirus and Respiratory Syncytial Virus: Viral Co-Detections, Genotypes and Risk Factors for Severe Disease",http://dx.doi.org/10.1371/journal.pone.0170200,PMC5240941,28095451,CC BY,"BACKGROUND: It is unclarified as to whether viral co-detection and human metapneumovirus (HMPV) genotypes relate to clinical manifestations in children with HMPV and lower respiratory tract infection (LRTI), and if the clinical course and risk factors for severe LRTI differ between HMPV and respiratory syncytial virus (RSV). METHODS: We prospectively enrolled hospitalized children aged <16 years with LRTI from 2006 to 2015. Children were clinically examined, and nasopharyngeal aspirates were analyzed using semi-quantitative, real-time polymerase chain reaction tests for HMPV, RSV and 17 other pathogens. HMPV-positive samples were genotyped. RESULTS: A total of 171 children had HMPV infection. HMPV-infected children with single virus (n = 106) and co-detections (n = 65) had similar clinical manifestations. No clinical differences were found between HMPV genotypes A (n = 67) and B (n = 80). The HMPV-infected children were older (median 17.2 months) than RSV-infected children (median 7.3 months, n = 859). Among single virus-infected children, no differences in age-adjusted LRTI diagnoses were found between HMPV and RSV. Age was an important factor for disease severity among single virus-infected children, where children <6 months old with HMPV had a milder disease than those with RSV, while in children 12–23 months old, the pattern was the opposite. In multivariable logistic regression analysis for each virus type, age ≥12 months (HMPV), and age <6 months (RSV), prematurity, ≥1 chronic disease and high viral loads of RSV, but not high HMPV viral loads, were risk factors for severe disease. CONCLUSIONS: Among hospitalized children with LRTI, HMPV manifests independently of viral co-detections and HMPV genotypes. Disease severity in HMPV- and RSV-infected children varies in relation to age. A history of prematurity and chronic disease increases the risk of severe LRTI among HMPV- and RSV-infected children.",2017 Jan 17,"['Moe, Nina', 'Krokstad, Sidsel', 'Stenseng, Inger Heimdal', 'Christensen, Andreas', 'Skanke, Lars Høsøien', 'Risnes, Kari Ravndal', 'Nordbø, Svein Arne', 'Døllner, Henrik']",PLoS One,,,True
509e9bda6a2f6b5525ba06641f8af156653a2aab,PMC,Intracranial Injection of Dengue Virus Induces Interferon Stimulated Genes and CD8(+) T Cell Infiltration by Sphingosine Kinase 1 Independent Pathways,http://dx.doi.org/10.1371/journal.pone.0169814,PMC5240945,28095439,CC BY,"We have previously reported that the absence of sphingosine kinase 1 (SK1) affects both dengue virus (DENV) infection and innate immune responses in vitro. Here we aimed to define SK1-dependancy of DENV-induced disease and the associated innate responses in vivo. The lack of a reliable mouse model with a fully competent interferon response for DENV infection is a challenge, and here we use an experimental model of DENV infection in the brain of immunocompetent mice. Intracranial injection of DENV-2 into C57BL/6 mice induced body weight loss and neurological symptoms which was associated with a high level of DENV RNA in the brain. Body weight loss and DENV RNA level tended to be greater in SK1(-/-) compared with wildtype (WT) mice. Brain infection with DENV-2 is associated with the induction of interferon-β (IFN-β) and IFN-stimulated gene (ISG) expression including viperin, Ifi27l2a, IRF7, and CXCL10 without any significant differences between WT and SK1(-/-) mice. The SK2 and sphingosine-1-phosphate (S1P) levels in the brain were unchanged by DENV infection or the lack of SK1. Histological analysis demonstrated the presence of a cellular infiltrate in DENV-infected brain with a significant increase in mRNA for CD8 but not CD4 suggesting this infiltrate is likely CD8(+) but not CD4(+) T-lymphocytes. This increase in T-cell infiltration was not affected by the lack of SK1. Overall, DENV-infection in the brain induces IFN and T-cell responses but does not influence the SK/S1P axis. In contrast to our observations in vitro, SK1 has no major influence on these responses following DENV-infection in the mouse brain.",2017 Jan 17,"['Al-Shujairi, Wisam H.', 'Clarke, Jennifer N.', 'Davies, Lorena T.', 'Alsharifi, Mohammed', 'Pitson, Stuart M.', 'Carr, Jillian M.']",PLoS One,,,True
2e84c01cad3e1f37940539a14a1f043fadf5b36d,PMC,Review of Participatory Epidemiology Practices in Animal Health (1980-2015) and Future Practice Directions,http://dx.doi.org/10.1371/journal.pone.0169198,PMC5240953,28095472,CC BY,"In this study we combined an inventory of the major applications, geographic regions and diseases covered by participatory epidemiology (PE) activities in the field of animal health since 1980, together with an email discussion forum with PE practitioners from different regions of the world. The inventory included the search of peer-reviewed papers, master and technical reports, conference proceedings, manuals, training materials and projects. The search resulted in a low number of PE activity results until the year 2000, followed by a considerable increase (especially from 2012). Most of the identified activities were implemented in Africa and Asia, and focused on surveillance, disease survey and prioritization, and disease control. Seventy-nine PE practitioners working predominantly in Africa, Asia and Europe (29, 22 and 18 respectively) contributed to the email discussion forum. They proposed various modifications to the existing PE definition and discussed different issues related to the applicatoin of PE, its institutionalization for use in policy development, as well as the priorities for future development. The need to increase the number of PE trained people together with some methodological developments and the application of this methodology in developed countries, were some of the points highlighted during the forum. These factors stress the importance of further developing PE as a useful approach for engaging communities in addressing animal and related public health risks.",2017 Jan 17,"['Allepuz, Alberto', 'de Balogh, Katinka', 'Aguanno, Ryan', 'Heilmann, Martin', 'Beltran-Alcrudo, Daniel']",PLoS One,,,True
45c82142062bfba189785a188b9adf1666d51e61,PMC,Review of Participatory Epidemiology Practices in Animal Health (1980-2015) and Future Practice Directions,http://dx.doi.org/10.1371/journal.pone.0169198,PMC5240953,28095472,CC BY,"In this study we combined an inventory of the major applications, geographic regions and diseases covered by participatory epidemiology (PE) activities in the field of animal health since 1980, together with an email discussion forum with PE practitioners from different regions of the world. The inventory included the search of peer-reviewed papers, master and technical reports, conference proceedings, manuals, training materials and projects. The search resulted in a low number of PE activity results until the year 2000, followed by a considerable increase (especially from 2012). Most of the identified activities were implemented in Africa and Asia, and focused on surveillance, disease survey and prioritization, and disease control. Seventy-nine PE practitioners working predominantly in Africa, Asia and Europe (29, 22 and 18 respectively) contributed to the email discussion forum. They proposed various modifications to the existing PE definition and discussed different issues related to the applicatoin of PE, its institutionalization for use in policy development, as well as the priorities for future development. The need to increase the number of PE trained people together with some methodological developments and the application of this methodology in developed countries, were some of the points highlighted during the forum. These factors stress the importance of further developing PE as a useful approach for engaging communities in addressing animal and related public health risks.",2017 Jan 17,"['Allepuz, Alberto', 'de Balogh, Katinka', 'Aguanno, Ryan', 'Heilmann, Martin', 'Beltran-Alcrudo, Daniel']",PLoS One,,,False
aeec15ca85a1bcf0bcab107dcd27e8d7cc412870,PMC,Review of Participatory Epidemiology Practices in Animal Health (1980-2015) and Future Practice Directions,http://dx.doi.org/10.1371/journal.pone.0169198,PMC5240953,28095472,CC BY,"In this study we combined an inventory of the major applications, geographic regions and diseases covered by participatory epidemiology (PE) activities in the field of animal health since 1980, together with an email discussion forum with PE practitioners from different regions of the world. The inventory included the search of peer-reviewed papers, master and technical reports, conference proceedings, manuals, training materials and projects. The search resulted in a low number of PE activity results until the year 2000, followed by a considerable increase (especially from 2012). Most of the identified activities were implemented in Africa and Asia, and focused on surveillance, disease survey and prioritization, and disease control. Seventy-nine PE practitioners working predominantly in Africa, Asia and Europe (29, 22 and 18 respectively) contributed to the email discussion forum. They proposed various modifications to the existing PE definition and discussed different issues related to the applicatoin of PE, its institutionalization for use in policy development, as well as the priorities for future development. The need to increase the number of PE trained people together with some methodological developments and the application of this methodology in developed countries, were some of the points highlighted during the forum. These factors stress the importance of further developing PE as a useful approach for engaging communities in addressing animal and related public health risks.",2017 Jan 17,"['Allepuz, Alberto', 'de Balogh, Katinka', 'Aguanno, Ryan', 'Heilmann, Martin', 'Beltran-Alcrudo, Daniel']",PLoS One,,,False
85a6db45e29636f124b7b1adc5230dfca7b37f9f,PMC,Review of Participatory Epidemiology Practices in Animal Health (1980-2015) and Future Practice Directions,http://dx.doi.org/10.1371/journal.pone.0169198,PMC5240953,28095472,CC BY,"In this study we combined an inventory of the major applications, geographic regions and diseases covered by participatory epidemiology (PE) activities in the field of animal health since 1980, together with an email discussion forum with PE practitioners from different regions of the world. The inventory included the search of peer-reviewed papers, master and technical reports, conference proceedings, manuals, training materials and projects. The search resulted in a low number of PE activity results until the year 2000, followed by a considerable increase (especially from 2012). Most of the identified activities were implemented in Africa and Asia, and focused on surveillance, disease survey and prioritization, and disease control. Seventy-nine PE practitioners working predominantly in Africa, Asia and Europe (29, 22 and 18 respectively) contributed to the email discussion forum. They proposed various modifications to the existing PE definition and discussed different issues related to the applicatoin of PE, its institutionalization for use in policy development, as well as the priorities for future development. The need to increase the number of PE trained people together with some methodological developments and the application of this methodology in developed countries, were some of the points highlighted during the forum. These factors stress the importance of further developing PE as a useful approach for engaging communities in addressing animal and related public health risks.",2017 Jan 17,"['Allepuz, Alberto', 'de Balogh, Katinka', 'Aguanno, Ryan', 'Heilmann, Martin', 'Beltran-Alcrudo, Daniel']",PLoS One,,,True
32c5106b9647b0d72f6c6fb15bf114e15d71736d,PMC,Novel Porcine Epidemic Diarrhea Virus (PEDV) Variants with Large Deletions in the Spike (S) Gene Coexist with PEDV Strains Possessing an Intact S Gene in Domestic Pigs in Japan: A New Disease Situation,http://dx.doi.org/10.1371/journal.pone.0170126,PMC5241010,28095455,CC BY,"Since late 2013, after an absence of seven years, outbreaks of porcine epidemic diarrhea virus (PEDV) infection have reemerged and swept rapidly across Japan, resulting in significant economic losses. In this study, we report the emergence, mixed infection, and genetic characterization of 15 novel field PEDV variants with large genomic deletions. The sizes of deletion varied between 582 nt (194 aa) and 648 nt (216 aa) at positions 28–714 (10–238) on the S gene (protein). Among 17 PEDV samples isolated from individual pigs, all of them contained at least two distinct genotypes with large genomic deletions, and 94.1% of them were found to consist of strains with an intact S gene. These variants were found in eight primary and nine recurrent outbreaks, and they might be associated with persistent PEDV infection in the farms. Full-length S and ORF3 genes of eight variants derived from 2 samples were characterized. This is the first report of mixed infections caused by various genotypes of PEDV and would be important for the studies of viral isolation, pathogenesis, and molecular epidemiology of the disease.",2017 Jan 17,"['Diep, Nguyen Van', 'Norimine, Junzo', 'Sueyoshi, Masuo', 'Lan, Nguyen Thi', 'Yamaguchi, Ryoji']",PLoS One,,,True
6dea708e7a2ddaca5049be8df41ce8dd58b2219a,PMC,Novel Porcine Epidemic Diarrhea Virus (PEDV) Variants with Large Deletions in the Spike (S) Gene Coexist with PEDV Strains Possessing an Intact S Gene in Domestic Pigs in Japan: A New Disease Situation,http://dx.doi.org/10.1371/journal.pone.0170126,PMC5241010,28095455,CC BY,"Since late 2013, after an absence of seven years, outbreaks of porcine epidemic diarrhea virus (PEDV) infection have reemerged and swept rapidly across Japan, resulting in significant economic losses. In this study, we report the emergence, mixed infection, and genetic characterization of 15 novel field PEDV variants with large genomic deletions. The sizes of deletion varied between 582 nt (194 aa) and 648 nt (216 aa) at positions 28–714 (10–238) on the S gene (protein). Among 17 PEDV samples isolated from individual pigs, all of them contained at least two distinct genotypes with large genomic deletions, and 94.1% of them were found to consist of strains with an intact S gene. These variants were found in eight primary and nine recurrent outbreaks, and they might be associated with persistent PEDV infection in the farms. Full-length S and ORF3 genes of eight variants derived from 2 samples were characterized. This is the first report of mixed infections caused by various genotypes of PEDV and would be important for the studies of viral isolation, pathogenesis, and molecular epidemiology of the disease.",2017 Jan 17,"['Diep, Nguyen Van', 'Norimine, Junzo', 'Sueyoshi, Masuo', 'Lan, Nguyen Thi', 'Yamaguchi, Ryoji']",PLoS One,,,False
954f70acea28240a3abe3cbaa7177de9ad34decf,PMC,Novel Porcine Epidemic Diarrhea Virus (PEDV) Variants with Large Deletions in the Spike (S) Gene Coexist with PEDV Strains Possessing an Intact S Gene in Domestic Pigs in Japan: A New Disease Situation,http://dx.doi.org/10.1371/journal.pone.0170126,PMC5241010,28095455,CC BY,"Since late 2013, after an absence of seven years, outbreaks of porcine epidemic diarrhea virus (PEDV) infection have reemerged and swept rapidly across Japan, resulting in significant economic losses. In this study, we report the emergence, mixed infection, and genetic characterization of 15 novel field PEDV variants with large genomic deletions. The sizes of deletion varied between 582 nt (194 aa) and 648 nt (216 aa) at positions 28–714 (10–238) on the S gene (protein). Among 17 PEDV samples isolated from individual pigs, all of them contained at least two distinct genotypes with large genomic deletions, and 94.1% of them were found to consist of strains with an intact S gene. These variants were found in eight primary and nine recurrent outbreaks, and they might be associated with persistent PEDV infection in the farms. Full-length S and ORF3 genes of eight variants derived from 2 samples were characterized. This is the first report of mixed infections caused by various genotypes of PEDV and would be important for the studies of viral isolation, pathogenesis, and molecular epidemiology of the disease.",2017 Jan 17,"['Diep, Nguyen Van', 'Norimine, Junzo', 'Sueyoshi, Masuo', 'Lan, Nguyen Thi', 'Yamaguchi, Ryoji']",PLoS One,,,False
977f8bf86c08dd49d32dc09682e69cd99b30f4f0,PMC,Integrative Analysis of Disease Signatures Shows Inflammation Disrupts Juvenile Experience-Dependent Cortical Plasticity,http://dx.doi.org/10.1523/ENEURO.0240-16.2016,PMC5241709,28101530,CC BY,"Throughout childhood and adolescence, periods of heightened neuroplasticity are critical for the development of healthy brain function and behavior. Given the high prevalence of neurodevelopmental disorders, such as autism, identifying disruptors of developmental plasticity represents an essential step for developing strategies for prevention and intervention. Applying a novel computational approach that systematically assessed connections between 436 transcriptional signatures of disease and multiple signatures of neuroplasticity, we identified inflammation as a common pathological process central to a diverse set of diseases predicted to dysregulate plasticity signatures. We tested the hypothesis that inflammation disrupts developmental cortical plasticity in vivo using the mouse ocular dominance model of experience-dependent plasticity in primary visual cortex. We found that the administration of systemic lipopolysaccharide suppressed plasticity during juvenile critical period with accompanying transcriptional changes in a particular set of molecular regulators within primary visual cortex. These findings suggest that inflammation may have unrecognized adverse consequences on the postnatal developmental trajectory and indicate that treating inflammation may reduce the burden of neurodevelopmental disorders.",2017 Jan 18,"['Smith, Milo R.', 'Burman, Poromendro', 'Sadahiro, Masato', 'Kidd, Brian A.', 'Dudley, Joel T.', 'Morishita, Hirofumi']",eNeuro,,,True
c2676bad025d5a255889b8a699c86711223e3a63,PMC,Triterpene Constituents of Euphorbia Erythradenia Bioss. and their Anti-HIV Activity,,PMC5242348,28228800,CC BY,"Phytochemical investigation of the aerial parts of Euphorbia erythradenia Bioss. (Euphorbiaceae), one of Iranian endemic Euphorbias, with particular attention to triterpene constituents, using methanol solvent extraction was carried out. Five known triterpenes, including four cycloartanes and oleanolic acid, were isolated for the first time and identified using NMR and Mass techniques. Anti HIV activity of the isolated triterpenes and ingenoid diterpenes was evaluated using single cycle replicable HIV-1 (SCR HIV-1) virions. Molecular features of the most active compound (IC(50) = 0.008 μM, CC(50) = 3.264 μM, TI = 380.64), which showed higher therapeutic index than nevirapine, was assessed using molecular docking. Docking studies demonstrated three hydrogen bonds between HIV-1 virion protease active site and this compound with a distance less than 3 A° which can be responsible for the observed anti HIV-1 activity.",2016 Winter,"['Ayatollahi, Abdul Majid', 'Zarei, Seyed Mohammad', 'Memarnejadian, Arash', 'Ghanadian, Mustafa', 'Heydarian Moghadam, Mohammad', 'Kobarfard, Farzad']",Iran J Pharm Res,,,True
3b5ea760c63aaff964de32541643d92c69dfc05e,PMC,Evaluation of Methods for the Concentration and Extraction of Viruses from Sewage in the Context of Metagenomic Sequencing,http://dx.doi.org/10.1371/journal.pone.0170199,PMC5242460,28099518,CC BY,"Viral sewage metagenomics is a novel field of study used for surveillance, epidemiological studies, and evaluation of waste water treatment efficiency. In raw sewage human waste is mixed with household, industrial and drainage water, and virus particles are, therefore, only found in low concentrations. This necessitates a step of sample concentration to allow for sensitive virus detection. Additionally, viruses harbor a large diversity of both surface and genome structures, which makes universal viral genomic extraction difficult. Current studies have tackled these challenges in many different ways employing a wide range of viral concentration and extraction procedures. However, there is limited knowledge of the efficacy and inherent biases associated with these methods in respect to viral sewage metagenomics, hampering the development of this field. By the use of next generation sequencing this study aimed to evaluate the efficiency of four commonly applied viral concentrations techniques (precipitation with polyethylene glycol, organic flocculation with skim milk, monolithic adsorption filtration and glass wool filtration) and extraction methods (Nucleospin RNA XS, QIAamp Viral RNA Mini Kit, NucliSENS(®) miniMAG(®), or PowerViral(®) Environmental RNA/DNA Isolation Kit) to determine the viriome in a sewage sample. We found a significant influence of concentration and extraction protocols on the detected viriome. The viral richness was largest in samples extracted with QIAamp Viral RNA Mini Kit or PowerViral(®) Environmental RNA/DNA Isolation Kit. Highest viral specificity were found in samples concentrated by precipitation with polyethylene glycol or extracted with Nucleospin RNA XS. Detection of viral pathogens depended on the method used. These results contribute to the understanding of method associated biases, within the field of viral sewage metagenomics, making evaluation of the current literature easier and helping with the design of future studies.",2017 Jan 18,"['Hjelmsø, Mathis Hjort', 'Hellmér, Maria', 'Fernandez-Cassi, Xavier', 'Timoneda, Natàlia', 'Lukjancenko, Oksana', 'Seidel, Michael', 'Elsässer, Dennis', 'Aarestrup, Frank M.', 'Löfström, Charlotta', 'Bofill-Mas, Sílvia', 'Abril, Josep F.', 'Girones, Rosina', 'Schultz, Anna Charlotte']",PLoS One,,,True
5b0cc630e700bec90ccc927c26b80cd4ce00ce51,PMC,Evaluation of Methods for the Concentration and Extraction of Viruses from Sewage in the Context of Metagenomic Sequencing,http://dx.doi.org/10.1371/journal.pone.0170199,PMC5242460,28099518,CC BY,"Viral sewage metagenomics is a novel field of study used for surveillance, epidemiological studies, and evaluation of waste water treatment efficiency. In raw sewage human waste is mixed with household, industrial and drainage water, and virus particles are, therefore, only found in low concentrations. This necessitates a step of sample concentration to allow for sensitive virus detection. Additionally, viruses harbor a large diversity of both surface and genome structures, which makes universal viral genomic extraction difficult. Current studies have tackled these challenges in many different ways employing a wide range of viral concentration and extraction procedures. However, there is limited knowledge of the efficacy and inherent biases associated with these methods in respect to viral sewage metagenomics, hampering the development of this field. By the use of next generation sequencing this study aimed to evaluate the efficiency of four commonly applied viral concentrations techniques (precipitation with polyethylene glycol, organic flocculation with skim milk, monolithic adsorption filtration and glass wool filtration) and extraction methods (Nucleospin RNA XS, QIAamp Viral RNA Mini Kit, NucliSENS(®) miniMAG(®), or PowerViral(®) Environmental RNA/DNA Isolation Kit) to determine the viriome in a sewage sample. We found a significant influence of concentration and extraction protocols on the detected viriome. The viral richness was largest in samples extracted with QIAamp Viral RNA Mini Kit or PowerViral(®) Environmental RNA/DNA Isolation Kit. Highest viral specificity were found in samples concentrated by precipitation with polyethylene glycol or extracted with Nucleospin RNA XS. Detection of viral pathogens depended on the method used. These results contribute to the understanding of method associated biases, within the field of viral sewage metagenomics, making evaluation of the current literature easier and helping with the design of future studies.",2017 Jan 18,"['Hjelmsø, Mathis Hjort', 'Hellmér, Maria', 'Fernandez-Cassi, Xavier', 'Timoneda, Natàlia', 'Lukjancenko, Oksana', 'Seidel, Michael', 'Elsässer, Dennis', 'Aarestrup, Frank M.', 'Löfström, Charlotta', 'Bofill-Mas, Sílvia', 'Abril, Josep F.', 'Girones, Rosina', 'Schultz, Anna Charlotte']",PLoS One,,,False
deb6ca906e5b3f08d1a20ab8ec3cb85b5617ce0d,PMC,Evaluation of Methods for the Concentration and Extraction of Viruses from Sewage in the Context of Metagenomic Sequencing,http://dx.doi.org/10.1371/journal.pone.0170199,PMC5242460,28099518,CC BY,"Viral sewage metagenomics is a novel field of study used for surveillance, epidemiological studies, and evaluation of waste water treatment efficiency. In raw sewage human waste is mixed with household, industrial and drainage water, and virus particles are, therefore, only found in low concentrations. This necessitates a step of sample concentration to allow for sensitive virus detection. Additionally, viruses harbor a large diversity of both surface and genome structures, which makes universal viral genomic extraction difficult. Current studies have tackled these challenges in many different ways employing a wide range of viral concentration and extraction procedures. However, there is limited knowledge of the efficacy and inherent biases associated with these methods in respect to viral sewage metagenomics, hampering the development of this field. By the use of next generation sequencing this study aimed to evaluate the efficiency of four commonly applied viral concentrations techniques (precipitation with polyethylene glycol, organic flocculation with skim milk, monolithic adsorption filtration and glass wool filtration) and extraction methods (Nucleospin RNA XS, QIAamp Viral RNA Mini Kit, NucliSENS(®) miniMAG(®), or PowerViral(®) Environmental RNA/DNA Isolation Kit) to determine the viriome in a sewage sample. We found a significant influence of concentration and extraction protocols on the detected viriome. The viral richness was largest in samples extracted with QIAamp Viral RNA Mini Kit or PowerViral(®) Environmental RNA/DNA Isolation Kit. Highest viral specificity were found in samples concentrated by precipitation with polyethylene glycol or extracted with Nucleospin RNA XS. Detection of viral pathogens depended on the method used. These results contribute to the understanding of method associated biases, within the field of viral sewage metagenomics, making evaluation of the current literature easier and helping with the design of future studies.",2017 Jan 18,"['Hjelmsø, Mathis Hjort', 'Hellmér, Maria', 'Fernandez-Cassi, Xavier', 'Timoneda, Natàlia', 'Lukjancenko, Oksana', 'Seidel, Michael', 'Elsässer, Dennis', 'Aarestrup, Frank M.', 'Löfström, Charlotta', 'Bofill-Mas, Sílvia', 'Abril, Josep F.', 'Girones, Rosina', 'Schultz, Anna Charlotte']",PLoS One,,,False
93300a0b0804ca348a6c38b9b8ba57ee17189944,PMC,Evaluation of Methods for the Concentration and Extraction of Viruses from Sewage in the Context of Metagenomic Sequencing,http://dx.doi.org/10.1371/journal.pone.0170199,PMC5242460,28099518,CC BY,"Viral sewage metagenomics is a novel field of study used for surveillance, epidemiological studies, and evaluation of waste water treatment efficiency. In raw sewage human waste is mixed with household, industrial and drainage water, and virus particles are, therefore, only found in low concentrations. This necessitates a step of sample concentration to allow for sensitive virus detection. Additionally, viruses harbor a large diversity of both surface and genome structures, which makes universal viral genomic extraction difficult. Current studies have tackled these challenges in many different ways employing a wide range of viral concentration and extraction procedures. However, there is limited knowledge of the efficacy and inherent biases associated with these methods in respect to viral sewage metagenomics, hampering the development of this field. By the use of next generation sequencing this study aimed to evaluate the efficiency of four commonly applied viral concentrations techniques (precipitation with polyethylene glycol, organic flocculation with skim milk, monolithic adsorption filtration and glass wool filtration) and extraction methods (Nucleospin RNA XS, QIAamp Viral RNA Mini Kit, NucliSENS(®) miniMAG(®), or PowerViral(®) Environmental RNA/DNA Isolation Kit) to determine the viriome in a sewage sample. We found a significant influence of concentration and extraction protocols on the detected viriome. The viral richness was largest in samples extracted with QIAamp Viral RNA Mini Kit or PowerViral(®) Environmental RNA/DNA Isolation Kit. Highest viral specificity were found in samples concentrated by precipitation with polyethylene glycol or extracted with Nucleospin RNA XS. Detection of viral pathogens depended on the method used. These results contribute to the understanding of method associated biases, within the field of viral sewage metagenomics, making evaluation of the current literature easier and helping with the design of future studies.",2017 Jan 18,"['Hjelmsø, Mathis Hjort', 'Hellmér, Maria', 'Fernandez-Cassi, Xavier', 'Timoneda, Natàlia', 'Lukjancenko, Oksana', 'Seidel, Michael', 'Elsässer, Dennis', 'Aarestrup, Frank M.', 'Löfström, Charlotta', 'Bofill-Mas, Sílvia', 'Abril, Josep F.', 'Girones, Rosina', 'Schultz, Anna Charlotte']",PLoS One,,,False
7abd95abecbc1f23e12b45fbdccde04655be1409,PMC,Evaluation of Methods for the Concentration and Extraction of Viruses from Sewage in the Context of Metagenomic Sequencing,http://dx.doi.org/10.1371/journal.pone.0170199,PMC5242460,28099518,CC BY,"Viral sewage metagenomics is a novel field of study used for surveillance, epidemiological studies, and evaluation of waste water treatment efficiency. In raw sewage human waste is mixed with household, industrial and drainage water, and virus particles are, therefore, only found in low concentrations. This necessitates a step of sample concentration to allow for sensitive virus detection. Additionally, viruses harbor a large diversity of both surface and genome structures, which makes universal viral genomic extraction difficult. Current studies have tackled these challenges in many different ways employing a wide range of viral concentration and extraction procedures. However, there is limited knowledge of the efficacy and inherent biases associated with these methods in respect to viral sewage metagenomics, hampering the development of this field. By the use of next generation sequencing this study aimed to evaluate the efficiency of four commonly applied viral concentrations techniques (precipitation with polyethylene glycol, organic flocculation with skim milk, monolithic adsorption filtration and glass wool filtration) and extraction methods (Nucleospin RNA XS, QIAamp Viral RNA Mini Kit, NucliSENS(®) miniMAG(®), or PowerViral(®) Environmental RNA/DNA Isolation Kit) to determine the viriome in a sewage sample. We found a significant influence of concentration and extraction protocols on the detected viriome. The viral richness was largest in samples extracted with QIAamp Viral RNA Mini Kit or PowerViral(®) Environmental RNA/DNA Isolation Kit. Highest viral specificity were found in samples concentrated by precipitation with polyethylene glycol or extracted with Nucleospin RNA XS. Detection of viral pathogens depended on the method used. These results contribute to the understanding of method associated biases, within the field of viral sewage metagenomics, making evaluation of the current literature easier and helping with the design of future studies.",2017 Jan 18,"['Hjelmsø, Mathis Hjort', 'Hellmér, Maria', 'Fernandez-Cassi, Xavier', 'Timoneda, Natàlia', 'Lukjancenko, Oksana', 'Seidel, Michael', 'Elsässer, Dennis', 'Aarestrup, Frank M.', 'Löfström, Charlotta', 'Bofill-Mas, Sílvia', 'Abril, Josep F.', 'Girones, Rosina', 'Schultz, Anna Charlotte']",PLoS One,,,False
401e744a57e5f64afbb6ce31d8725155c2b0b7ee,PMC,Evaluation of Methods for the Concentration and Extraction of Viruses from Sewage in the Context of Metagenomic Sequencing,http://dx.doi.org/10.1371/journal.pone.0170199,PMC5242460,28099518,CC BY,"Viral sewage metagenomics is a novel field of study used for surveillance, epidemiological studies, and evaluation of waste water treatment efficiency. In raw sewage human waste is mixed with household, industrial and drainage water, and virus particles are, therefore, only found in low concentrations. This necessitates a step of sample concentration to allow for sensitive virus detection. Additionally, viruses harbor a large diversity of both surface and genome structures, which makes universal viral genomic extraction difficult. Current studies have tackled these challenges in many different ways employing a wide range of viral concentration and extraction procedures. However, there is limited knowledge of the efficacy and inherent biases associated with these methods in respect to viral sewage metagenomics, hampering the development of this field. By the use of next generation sequencing this study aimed to evaluate the efficiency of four commonly applied viral concentrations techniques (precipitation with polyethylene glycol, organic flocculation with skim milk, monolithic adsorption filtration and glass wool filtration) and extraction methods (Nucleospin RNA XS, QIAamp Viral RNA Mini Kit, NucliSENS(®) miniMAG(®), or PowerViral(®) Environmental RNA/DNA Isolation Kit) to determine the viriome in a sewage sample. We found a significant influence of concentration and extraction protocols on the detected viriome. The viral richness was largest in samples extracted with QIAamp Viral RNA Mini Kit or PowerViral(®) Environmental RNA/DNA Isolation Kit. Highest viral specificity were found in samples concentrated by precipitation with polyethylene glycol or extracted with Nucleospin RNA XS. Detection of viral pathogens depended on the method used. These results contribute to the understanding of method associated biases, within the field of viral sewage metagenomics, making evaluation of the current literature easier and helping with the design of future studies.",2017 Jan 18,"['Hjelmsø, Mathis Hjort', 'Hellmér, Maria', 'Fernandez-Cassi, Xavier', 'Timoneda, Natàlia', 'Lukjancenko, Oksana', 'Seidel, Michael', 'Elsässer, Dennis', 'Aarestrup, Frank M.', 'Löfström, Charlotta', 'Bofill-Mas, Sílvia', 'Abril, Josep F.', 'Girones, Rosina', 'Schultz, Anna Charlotte']",PLoS One,,,False
b501504425171d4c2f144677b3d7610c4479b0b6,PMC,Evaluation of Methods for the Concentration and Extraction of Viruses from Sewage in the Context of Metagenomic Sequencing,http://dx.doi.org/10.1371/journal.pone.0170199,PMC5242460,28099518,CC BY,"Viral sewage metagenomics is a novel field of study used for surveillance, epidemiological studies, and evaluation of waste water treatment efficiency. In raw sewage human waste is mixed with household, industrial and drainage water, and virus particles are, therefore, only found in low concentrations. This necessitates a step of sample concentration to allow for sensitive virus detection. Additionally, viruses harbor a large diversity of both surface and genome structures, which makes universal viral genomic extraction difficult. Current studies have tackled these challenges in many different ways employing a wide range of viral concentration and extraction procedures. However, there is limited knowledge of the efficacy and inherent biases associated with these methods in respect to viral sewage metagenomics, hampering the development of this field. By the use of next generation sequencing this study aimed to evaluate the efficiency of four commonly applied viral concentrations techniques (precipitation with polyethylene glycol, organic flocculation with skim milk, monolithic adsorption filtration and glass wool filtration) and extraction methods (Nucleospin RNA XS, QIAamp Viral RNA Mini Kit, NucliSENS(®) miniMAG(®), or PowerViral(®) Environmental RNA/DNA Isolation Kit) to determine the viriome in a sewage sample. We found a significant influence of concentration and extraction protocols on the detected viriome. The viral richness was largest in samples extracted with QIAamp Viral RNA Mini Kit or PowerViral(®) Environmental RNA/DNA Isolation Kit. Highest viral specificity were found in samples concentrated by precipitation with polyethylene glycol or extracted with Nucleospin RNA XS. Detection of viral pathogens depended on the method used. These results contribute to the understanding of method associated biases, within the field of viral sewage metagenomics, making evaluation of the current literature easier and helping with the design of future studies.",2017 Jan 18,"['Hjelmsø, Mathis Hjort', 'Hellmér, Maria', 'Fernandez-Cassi, Xavier', 'Timoneda, Natàlia', 'Lukjancenko, Oksana', 'Seidel, Michael', 'Elsässer, Dennis', 'Aarestrup, Frank M.', 'Löfström, Charlotta', 'Bofill-Mas, Sílvia', 'Abril, Josep F.', 'Girones, Rosina', 'Schultz, Anna Charlotte']",PLoS One,,,False
5b3201cc14837e36fc747be7810d0b9c017e98c4,PMC,Evaluation of Methods for the Concentration and Extraction of Viruses from Sewage in the Context of Metagenomic Sequencing,http://dx.doi.org/10.1371/journal.pone.0170199,PMC5242460,28099518,CC BY,"Viral sewage metagenomics is a novel field of study used for surveillance, epidemiological studies, and evaluation of waste water treatment efficiency. In raw sewage human waste is mixed with household, industrial and drainage water, and virus particles are, therefore, only found in low concentrations. This necessitates a step of sample concentration to allow for sensitive virus detection. Additionally, viruses harbor a large diversity of both surface and genome structures, which makes universal viral genomic extraction difficult. Current studies have tackled these challenges in many different ways employing a wide range of viral concentration and extraction procedures. However, there is limited knowledge of the efficacy and inherent biases associated with these methods in respect to viral sewage metagenomics, hampering the development of this field. By the use of next generation sequencing this study aimed to evaluate the efficiency of four commonly applied viral concentrations techniques (precipitation with polyethylene glycol, organic flocculation with skim milk, monolithic adsorption filtration and glass wool filtration) and extraction methods (Nucleospin RNA XS, QIAamp Viral RNA Mini Kit, NucliSENS(®) miniMAG(®), or PowerViral(®) Environmental RNA/DNA Isolation Kit) to determine the viriome in a sewage sample. We found a significant influence of concentration and extraction protocols on the detected viriome. The viral richness was largest in samples extracted with QIAamp Viral RNA Mini Kit or PowerViral(®) Environmental RNA/DNA Isolation Kit. Highest viral specificity were found in samples concentrated by precipitation with polyethylene glycol or extracted with Nucleospin RNA XS. Detection of viral pathogens depended on the method used. These results contribute to the understanding of method associated biases, within the field of viral sewage metagenomics, making evaluation of the current literature easier and helping with the design of future studies.",2017 Jan 18,"['Hjelmsø, Mathis Hjort', 'Hellmér, Maria', 'Fernandez-Cassi, Xavier', 'Timoneda, Natàlia', 'Lukjancenko, Oksana', 'Seidel, Michael', 'Elsässer, Dennis', 'Aarestrup, Frank M.', 'Löfström, Charlotta', 'Bofill-Mas, Sílvia', 'Abril, Josep F.', 'Girones, Rosina', 'Schultz, Anna Charlotte']",PLoS One,,,False
76d3c799a37ac490dde80c4ba90fca49e1cc206d,PMC,Evaluation of Methods for the Concentration and Extraction of Viruses from Sewage in the Context of Metagenomic Sequencing,http://dx.doi.org/10.1371/journal.pone.0170199,PMC5242460,28099518,CC BY,"Viral sewage metagenomics is a novel field of study used for surveillance, epidemiological studies, and evaluation of waste water treatment efficiency. In raw sewage human waste is mixed with household, industrial and drainage water, and virus particles are, therefore, only found in low concentrations. This necessitates a step of sample concentration to allow for sensitive virus detection. Additionally, viruses harbor a large diversity of both surface and genome structures, which makes universal viral genomic extraction difficult. Current studies have tackled these challenges in many different ways employing a wide range of viral concentration and extraction procedures. However, there is limited knowledge of the efficacy and inherent biases associated with these methods in respect to viral sewage metagenomics, hampering the development of this field. By the use of next generation sequencing this study aimed to evaluate the efficiency of four commonly applied viral concentrations techniques (precipitation with polyethylene glycol, organic flocculation with skim milk, monolithic adsorption filtration and glass wool filtration) and extraction methods (Nucleospin RNA XS, QIAamp Viral RNA Mini Kit, NucliSENS(®) miniMAG(®), or PowerViral(®) Environmental RNA/DNA Isolation Kit) to determine the viriome in a sewage sample. We found a significant influence of concentration and extraction protocols on the detected viriome. The viral richness was largest in samples extracted with QIAamp Viral RNA Mini Kit or PowerViral(®) Environmental RNA/DNA Isolation Kit. Highest viral specificity were found in samples concentrated by precipitation with polyethylene glycol or extracted with Nucleospin RNA XS. Detection of viral pathogens depended on the method used. These results contribute to the understanding of method associated biases, within the field of viral sewage metagenomics, making evaluation of the current literature easier and helping with the design of future studies.",2017 Jan 18,"['Hjelmsø, Mathis Hjort', 'Hellmér, Maria', 'Fernandez-Cassi, Xavier', 'Timoneda, Natàlia', 'Lukjancenko, Oksana', 'Seidel, Michael', 'Elsässer, Dennis', 'Aarestrup, Frank M.', 'Löfström, Charlotta', 'Bofill-Mas, Sílvia', 'Abril, Josep F.', 'Girones, Rosina', 'Schultz, Anna Charlotte']",PLoS One,,,False
ffe06dc98b684ff0d57b663d19ee04b921210c1b,PMC,Evaluation of Methods for the Concentration and Extraction of Viruses from Sewage in the Context of Metagenomic Sequencing,http://dx.doi.org/10.1371/journal.pone.0170199,PMC5242460,28099518,CC BY,"Viral sewage metagenomics is a novel field of study used for surveillance, epidemiological studies, and evaluation of waste water treatment efficiency. In raw sewage human waste is mixed with household, industrial and drainage water, and virus particles are, therefore, only found in low concentrations. This necessitates a step of sample concentration to allow for sensitive virus detection. Additionally, viruses harbor a large diversity of both surface and genome structures, which makes universal viral genomic extraction difficult. Current studies have tackled these challenges in many different ways employing a wide range of viral concentration and extraction procedures. However, there is limited knowledge of the efficacy and inherent biases associated with these methods in respect to viral sewage metagenomics, hampering the development of this field. By the use of next generation sequencing this study aimed to evaluate the efficiency of four commonly applied viral concentrations techniques (precipitation with polyethylene glycol, organic flocculation with skim milk, monolithic adsorption filtration and glass wool filtration) and extraction methods (Nucleospin RNA XS, QIAamp Viral RNA Mini Kit, NucliSENS(®) miniMAG(®), or PowerViral(®) Environmental RNA/DNA Isolation Kit) to determine the viriome in a sewage sample. We found a significant influence of concentration and extraction protocols on the detected viriome. The viral richness was largest in samples extracted with QIAamp Viral RNA Mini Kit or PowerViral(®) Environmental RNA/DNA Isolation Kit. Highest viral specificity were found in samples concentrated by precipitation with polyethylene glycol or extracted with Nucleospin RNA XS. Detection of viral pathogens depended on the method used. These results contribute to the understanding of method associated biases, within the field of viral sewage metagenomics, making evaluation of the current literature easier and helping with the design of future studies.",2017 Jan 18,"['Hjelmsø, Mathis Hjort', 'Hellmér, Maria', 'Fernandez-Cassi, Xavier', 'Timoneda, Natàlia', 'Lukjancenko, Oksana', 'Seidel, Michael', 'Elsässer, Dennis', 'Aarestrup, Frank M.', 'Löfström, Charlotta', 'Bofill-Mas, Sílvia', 'Abril, Josep F.', 'Girones, Rosina', 'Schultz, Anna Charlotte']",PLoS One,,,False
40a57ffe8adda95a13b552b630b13d76344f666c,PMC,Elimination of Porcine Epidemic Diarrhea Virus in an Animal Feed Manufacturing Facility,http://dx.doi.org/10.1371/journal.pone.0169612,PMC5242487,28099453,CC BY,"Porcine Epidemic Diarrhea Virus (PEDV) was the first virus of wide scale concern to be linked to possible transmission by livestock feed or ingredients. Measures to exclude pathogens, prevent cross-contamination, and actively reduce the pathogenic load of feed and ingredients are being developed. However, research thus far has focused on the role of chemicals or thermal treatment to reduce the RNA in the actual feedstuffs, and has not addressed potential residual contamination within the manufacturing facility that may lead to continuous contamination of finished feeds. The purpose of this experiment was to evaluate the use of a standardized protocol to sanitize an animal feed manufacturing facility contaminated with PEDV. Environmental swabs were collected throughout the facility during the manufacturing of a swine diet inoculated with PEDV. To monitor facility contamination of the virus, swabs were collected at: 1) baseline prior to inoculation, 2) after production of the inoculated feed, 3) after application of a quaternary ammonium-glutaraldehyde blend cleaner, 4) after application of a sodium hypochlorite sanitizing solution, and 5) after facility heat-up to 60°C for 48 hours. Decontamination step, surface, type, zone and their interactions were all found to impact the quantity of detectable PEDV RNA (P < 0.05). As expected, all samples collected from equipment surfaces contained PEDV RNA after production of the contaminated feed. Additionally, the majority of samples collected from non-direct feed contact surfaces were also positive for PEDV RNA after the production of the contaminated feed, emphasizing the potential role dust plays in cross-contamination of pathogen throughout a manufacturing facility. Application of the cleaner, sanitizer, and heat were effective at reducing PEDV genomic material (P < 0.05), but did not completely eliminate it.",2017 Jan 18,"['Huss, Anne R.', 'Schumacher, Loni L.', 'Cochrane, Roger A.', 'Poulsen, Elizabeth', 'Bai, Jianfa', 'Woodworth, Jason C.', 'Dritz, Steve S.', 'Stark, Charles R.', 'Jones, Cassandra K.']",PLoS One,,,True
d474315fbb8b2c284039f0caec40aaa334db068b,PMC,Alternative Polyadenylation of Human Bocavirus at Its 3′ End Is Regulated by Multiple Elements and Affects Capsid Expression,http://dx.doi.org/10.1128/JVI.02026-16,PMC5244319,27881651,CC BY,"Alternative processing of human bocavirus (HBoV) P5 promoter-transcribed RNA is critical for generating the structural and nonstructural protein-encoding mRNA transcripts. The regulatory mechanism by which HBoV RNA transcripts are polyadenylated at proximal [(pA)p] or distal [(pA)d] polyadenylation sites is still unclear. We constructed a recombinant HBoV infectious clone to study the alternative polyadenylation regulation of HBoV. Surprisingly, in addition to the reported distal polyadenylation site, (pA)d, a novel distal polyadenylation site, (pA)d2, which is located in the right-end hairpin (REH), was identified during infectious clone transfection or recombinant virus infection. (pA)d2 does not contain typical hexanucleotide polyadenylation signal, upstream elements (USE), or downstream elements (DSE) according to sequence analysis. Further study showed that HBoV nonstructural protein NS1, REH, and cis elements of (pA)d were necessary and sufficient for efficient polyadenylation at (pA)d2. The distance and sequences between (pA)d and (pA)d2 also played a key role in the regulation of polyadenylation at (pA)d2. Finally, we demonstrated that efficient polyadenylation at (pA)d2 resulted in increased HBoV capsid mRNA transcripts and protein translation. Thus, our study revealed that all the bocaviruses have distal poly(A) signals on the right-end palindromic terminus, and alternative polyadenylation at the HBoV 3′ end regulates its capsid expression. IMPORTANCE The distal polyadenylation site, (pA)d, of HBoV is located about 400 nucleotides (nt) from the right-end palindromic terminus, which is different from those of bovine parvovirus (BPV) and canine minute virus (MVC) in the same genus whose distal polyadenylation is located in the right-end stem-loop structure. A novel polyadenylation site, (pA)d2, was identified in the right-end hairpin of HBoV during infectious clone transfection or recombinant virus infection. Sequence analysis showed that (pA)d2 does not contain typical polyadenylation signals, and the last 42 nt form a stem-loop structure which is almost identical to that of MVC. Further study showed that NS1, REH, and cis elements of (pA)d are required for efficient polyadenylation at (pA)d2. Polyadenylation at (pA)d2 enhances capsid expression. Our study demonstrates alternative polyadenylation at the 3′ end of HBoV and suggests an additional mechanism by which capsid expression is regulated.",2017 Jan 18,"['Hao, Sujuan', 'Zhang, Junmei', 'Chen, Zhen', 'Xu, Huanzhou', 'Wang, Hanzhong', 'Guan, Wuxiang']",J Virol,,,True
bd78c67dd1bf9aea39f8fb3a1fe1761628dbe422,PMC,Activation of COX-2/PGE(2) Promotes Sapovirus Replication via the Inhibition of Nitric Oxide Production,http://dx.doi.org/10.1128/JVI.01656-16,PMC5244346,27881647,CC BY,"Enteric caliciviruses in the genera Norovirus and Sapovirus are important pathogens that cause severe acute gastroenteritis in both humans and animals. Cyclooxygenases (COXs) and their final product, prostaglandin E(2) (PGE(2)), are known to play important roles in the modulation of both the host response to infection and the replicative cycles of several viruses. However, the precise mechanism(s) by which the COX/PGE(2) pathway regulates sapovirus replication remains largely unknown. In this study, infection with porcine sapovirus (PSaV) strain Cowden, the only cultivable virus within the genus Sapovirus, markedly increased COX-2 mRNA and protein levels at 24 and 36 h postinfection (hpi), with only a transient increase in COX-1 levels seen at 24 hpi. The treatment of cells with pharmacological inhibitors, such as nonsteroidal anti-inflammatory drugs or small interfering RNAs (siRNAs) against COX-1 and COX-2, significantly reduced PGE(2) production, as well as PSaV replication. Expression of the viral proteins VPg and ProPol was associated with activation of the COX/PGE(2) pathway. We observed that pharmacological inhibition of COX-2 dramatically increased NO production, causing a reduction in PSaV replication that could be restored by inhibition of nitric oxide synthase via the inhibitor N-nitro-l-methyl-arginine ester. This study identified a pivotal role for the COX/PGE(2) pathway in the regulation of NO production during the sapovirus life cycle, providing new insights into the life cycle of this poorly characterized family of viruses. Our findings also reveal potential new targets for treatment of sapovirus infection. IMPORTANCE Sapoviruses are among the major etiological agents of acute gastroenteritis in both humans and animals, but little is known about sapovirus host factor requirements. Here, using only cultivable porcine sapovirus (PSaV) strain Cowden, we demonstrate that PSaV induced the vitalization of the cyclooxygenase (COX) and prostaglandin E(2) (PGE(2)) pathway. Targeting of COX-1/2 using nonsteroidal anti-inflammatory drugs (NSAIDs) such as the COX-1/2 inhibitor indomethacin and the COX-2-specific inhibitors NS-398 and celecoxib or siRNAs targeting COXs, inhibited PSaV replication. Expression of the viral proteins VPg and ProPol was associated with activation of the COX/PGE(2) pathway. We further demonstrate that the production of PGE(2) provides a protective effect against the antiviral effector mechanism of nitric oxide. Our findings uncover a new mechanism by which PSaV manipulates the host cell to provide an environment suitable for efficient viral growth, which in turn can be a new target for treatment of sapovirus infection.",2017 Jan 18,"['Alfajaro, Mia Madel', 'Choi, Jong-Soon', 'Kim, Deok-Song', 'Seo, Ja-Young', 'Kim, Ji-Yun', 'Park, Jun-Gyu', 'Soliman, Mahmoud', 'Baek, Yeong-Bin', 'Cho, Eun-Hyo', 'Kwon, Joseph', 'Kwon, Hyung-Jun', 'Park, Su-Jin', 'Lee, Woo Song', 'Kang, Mun-Il', 'Hosmillo, Myra', 'Goodfellow, Ian', 'Cho, Kyoung-Oh']",J Virol,,,True
1f92a01ead66646392c85f3abe57d3ea5ef8125a,PMC,Viral Phylogenomics Using an Alignment-Free Method: A Three-Step Approach to Determine Optimal Length of k-mer,http://dx.doi.org/10.1038/srep40712,PMC5244389,28102365,CC BY,"The development of rapid, economical genome sequencing has shed new light on the classification of viruses. As of October 2016, the National Center for Biotechnology Information (NCBI) database contained >2 million viral genome sequences and a reference set of ~4000 viral genome sequences that cover a wide range of known viral families. Whole-genome sequences can be used to improve viral classification and provide insight into the viral “tree of life”. However, due to the lack of evolutionary conservation amongst diverse viruses, it is not feasible to build a viral tree of life using traditional phylogenetic methods based on conserved proteins. In this study, we used an alignment-free method that uses k-mers as genomic features for a large-scale comparison of complete viral genomes available in RefSeq. To determine the optimal feature length, k (an essential step in constructing a meaningful dendrogram), we designed a comprehensive strategy that combines three approaches: (1) cumulative relative entropy, (2) average number of common features among genomes, and (3) the Shannon diversity index. This strategy was used to determine k for all 3,905 complete viral genomes in RefSeq. The resulting dendrogram shows consistency with the viral taxonomy of the ICTV and the Baltimore classification of viruses.",2017 Jan 19,"['Zhang, Qian', 'Jun, Se-Ran', 'Leuze, Michael', 'Ussery, David', 'Nookaew, Intawat']",Sci Rep,,,True
e612e6b0722c00c50364ae2bff335aed11edcb93,PMC,Viral Phylogenomics Using an Alignment-Free Method: A Three-Step Approach to Determine Optimal Length of k-mer,http://dx.doi.org/10.1038/srep40712,PMC5244389,28102365,CC BY,"The development of rapid, economical genome sequencing has shed new light on the classification of viruses. As of October 2016, the National Center for Biotechnology Information (NCBI) database contained >2 million viral genome sequences and a reference set of ~4000 viral genome sequences that cover a wide range of known viral families. Whole-genome sequences can be used to improve viral classification and provide insight into the viral “tree of life”. However, due to the lack of evolutionary conservation amongst diverse viruses, it is not feasible to build a viral tree of life using traditional phylogenetic methods based on conserved proteins. In this study, we used an alignment-free method that uses k-mers as genomic features for a large-scale comparison of complete viral genomes available in RefSeq. To determine the optimal feature length, k (an essential step in constructing a meaningful dendrogram), we designed a comprehensive strategy that combines three approaches: (1) cumulative relative entropy, (2) average number of common features among genomes, and (3) the Shannon diversity index. This strategy was used to determine k for all 3,905 complete viral genomes in RefSeq. The resulting dendrogram shows consistency with the viral taxonomy of the ICTV and the Baltimore classification of viruses.",2017 Jan 19,"['Zhang, Qian', 'Jun, Se-Ran', 'Leuze, Michael', 'Ussery, David', 'Nookaew, Intawat']",Sci Rep,,,False
59ea2e637fd9eaa8a64d10c6594f9404ec709bbf,PMC,Dual RNA-seq reveals viral infections in asthmatic children without respiratory illness which are associated with changes in the airway transcriptome,http://dx.doi.org/10.1186/s13059-016-1140-8,PMC5244706,28103897,CC BY,"BACKGROUND: Respiratory illness caused by viral infection is associated with the development and exacerbation of childhood asthma. Little is known about the effects of respiratory viral infections in the absence of illness. Using quantitative PCR (qPCR) for common respiratory viruses and for two genes known to be highly upregulated in viral infections (CCL8/CXCL11), we screened 92 asthmatic and 69 healthy children without illness for respiratory virus infections. RESULTS: We found 21 viral qPCR-positive and 2 suspected virus-infected subjects with high expression of CCL8/CXCL11. We applied a dual RNA-seq workflow to these subjects, together with 25 viral qPCR-negative subjects, to compare qPCR with sequencing-based virus detection and to generate the airway transcriptome for analysis. RNA-seq virus detection achieved 86% sensitivity when compared to qPCR-based screening. We detected additional respiratory viruses in the two CCL8/CXCL11-high subjects and in two of the qPCR-negative subjects. Viral read counts varied widely and were used to stratify subjects into Virus-High and Virus-Low groups. Examination of the host airway transcriptome found that the Virus-High group was characterized by immune cell airway infiltration, downregulation of cilia genes, and dampening of type 2 inflammation. Even the Virus-Low group was differentiated from the No-Virus group by 100 genes, some involved in eIF2 signaling. CONCLUSIONS: Respiratory virus infection without illness is not innocuous but may determine the airway function of these subjects by driving immune cell airway infiltration, cellular remodeling, and alteration of asthmogenic gene expression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-1140-8) contains supplementary material, which is available to authorized users.",2017 Jan 19,"['Wesolowska-Andersen, Agata', 'Everman, Jamie L.', 'Davidson, Rebecca', 'Rios, Cydney', 'Herrin, Rachelle', 'Eng, Celeste', 'Janssen, William J.', 'Liu, Andrew H.', 'Oh, Sam S.', 'Kumar, Rajesh', 'Fingerlin, Tasha E.', 'Rodriguez-Santana, Jose', 'Burchard, Esteban G.', 'Seibold, Max A.']",Genome Biol,,,False
46408d6638c45017e1dc70ef72bc0373c5514942,PMC,Dual RNA-seq reveals viral infections in asthmatic children without respiratory illness which are associated with changes in the airway transcriptome,http://dx.doi.org/10.1186/s13059-016-1140-8,PMC5244706,28103897,CC BY,"BACKGROUND: Respiratory illness caused by viral infection is associated with the development and exacerbation of childhood asthma. Little is known about the effects of respiratory viral infections in the absence of illness. Using quantitative PCR (qPCR) for common respiratory viruses and for two genes known to be highly upregulated in viral infections (CCL8/CXCL11), we screened 92 asthmatic and 69 healthy children without illness for respiratory virus infections. RESULTS: We found 21 viral qPCR-positive and 2 suspected virus-infected subjects with high expression of CCL8/CXCL11. We applied a dual RNA-seq workflow to these subjects, together with 25 viral qPCR-negative subjects, to compare qPCR with sequencing-based virus detection and to generate the airway transcriptome for analysis. RNA-seq virus detection achieved 86% sensitivity when compared to qPCR-based screening. We detected additional respiratory viruses in the two CCL8/CXCL11-high subjects and in two of the qPCR-negative subjects. Viral read counts varied widely and were used to stratify subjects into Virus-High and Virus-Low groups. Examination of the host airway transcriptome found that the Virus-High group was characterized by immune cell airway infiltration, downregulation of cilia genes, and dampening of type 2 inflammation. Even the Virus-Low group was differentiated from the No-Virus group by 100 genes, some involved in eIF2 signaling. CONCLUSIONS: Respiratory virus infection without illness is not innocuous but may determine the airway function of these subjects by driving immune cell airway infiltration, cellular remodeling, and alteration of asthmogenic gene expression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-1140-8) contains supplementary material, which is available to authorized users.",2017 Jan 19,"['Wesolowska-Andersen, Agata', 'Everman, Jamie L.', 'Davidson, Rebecca', 'Rios, Cydney', 'Herrin, Rachelle', 'Eng, Celeste', 'Janssen, William J.', 'Liu, Andrew H.', 'Oh, Sam S.', 'Kumar, Rajesh', 'Fingerlin, Tasha E.', 'Rodriguez-Santana, Jose', 'Burchard, Esteban G.', 'Seibold, Max A.']",Genome Biol,,,True
dc320a349f137013cc728b319144588e3854cb20,PMC,A Novel Mechanism Underlying the Innate Immune Response Induction upon Viral-Dependent Replication of Host Cell mRNA: A Mistake of +sRNA Viruses' Replicases,http://dx.doi.org/10.3389/fcimb.2017.00005,PMC5247633,28164038,CC BY,"Viruses are lifeless particles designed for setting virus-host interactome assuring a new generation of virions for dissemination. This interactome generates a pressure on host organisms evolving mechanisms to neutralize viral infection, which places the pressure back onto virus, a process known as virus-host cell co-evolution. Positive-single stranded RNA (+sRNA) viruses are an important group of viral agents illustrating this interesting phenomenon. During replication, their genomic +sRNA is employed as template for translation of viral proteins; among them the RNA-dependent RNA polymerase (RdRp) is responsible of viral genome replication originating double-strand RNA molecules (dsRNA) as intermediates, which accumulate representing a potent threat for cellular dsRNA receptors to initiate an antiviral response. A common feature shared by these viruses is their ability to rearrange cellular membranes to serve as platforms for genome replication and assembly of new virions, supporting replication efficiency increase by concentrating critical factors and protecting the viral genome from host anti-viral systems. This review summarizes current knowledge regarding cellular dsRNA receptors and describes prototype viruses developing replication niches inside rearranged membranes. However, for several viral agents it's been observed both, a complex rearrangement of cellular membranes and a strong innate immune antiviral response induction. So, we have included recent data explaining the mechanism by, even though viruses have evolved elegant hideouts, host cells are still able to develop dsRNA receptors-dependent antiviral response.",2017 Jan 20,"['Delgui, Laura R.', 'Colombo, María I.']",Front Cell Infect Microbiol,,,True
d940acd1f38f4b26cf2a7aeb4212f6854450ed0a,PMC,Improvement of Therapeutic Efficacy of Oral Immunotherapy in Combination with Regulatory T Cell-Inducer Kakkonto in a Murine Food Allergy Model,http://dx.doi.org/10.1371/journal.pone.0170577,PMC5249179,28107533,CC BY,"Oral immunotherapy (OIT) has been considered a promising approach for food allergies (FAs). However, the current OIT strategy is limited in terms of the long-term efficacy and safety. We have previously demonstrated that kakkonto, a traditional Japanese herbal medicine, suppresses the occurrence of allergic symptoms in a murine model of ovalbumin (OVA)-induced FA, which is attributed to the induction of the Foxp3(+) CD4(+) regulatory T cells. In this study, we established an OIT model using the FA mice with already established allergic symptoms and determined whether kakkonto could improve the efficacy of OIT. The OIT method consisted of initially administrating a very small amount of OVA and slowly increasing the amount. Allergic symptoms decreased in the OIT-treated FA mice. OIT significantly downregulated Th2 immune response-related gene expression in the FA mouse colon, and decreased the level of mouse mast cell protease-1, a marker of mast cell degranulation in the FA mouse plasma. Moreover, the concomitant use of kakkonto significantly enhanced the effectiveness of OIT on the allergic symptoms, and the combination therapy further suppressed the Th2 immune responses and the mast cell degranulation. In addition, OIT significantly increased the population of Foxp3(+) CD4(+) regulatory T cells in the FA mouse colon, and this population was further increased by OIT in combination with kakkonto. Furthermore, the combined therapy with kakkonto reduced the expression of RA-degrading enzyme CYP26B1 mRNA in the FA mouse colon. These findings indicated that the combination of OIT with kakkonto represents a promising approach for FA treatment.",2017 Jan 20,"['Nagata, Yuka', 'Yamamoto, Takeshi', 'Hayashi, Michie', 'Hayashi, Shusaku', 'Kadowaki, Makoto']",PLoS One,,,True
1aef4c8a0b31ddf10ab37a448fc90808218fa9d8,PMC,Multiple sclerosis: experimental models and reality,http://dx.doi.org/10.1007/s00401-016-1631-4,PMC5250666,27766432,CC BY,"One of the most frequent statements, provided in different variations in the introduction of experimental studies on multiple sclerosis (MS), is that “Multiple sclerosis is a demyelinating autoimmune disease and experimental autoimmune encephalomyelitis (EAE) is a suitable model to study its pathogenesis”. However, so far, no single experimental model covers the entire spectrum of the clinical, pathological, or immunological features of the disease. Many different models are available, which proved to be highly useful for studying different aspects of inflammation, demyelination, remyelination, and neurodegeneration in the central nervous system. However, the relevance of results from such models for MS pathogenesis has to be critically validated. Current EAE models are mainly based on inflammation, induced by auto-reactive CD4(+) T-cells, and these models reflect important aspects of MS. However, pathological data and results from clinical trials in MS indicate that CD8(+) T-cells and B-lymphocytes may play an important role in propagating inflammation and tissue damage in established MS. Viral models may reflect key features of MS-like inflammatory demyelination, but are difficult to use due to their very complex pathogenesis, involving direct virus-induced and immune-mediated mechanisms. Furthermore, evidence for a role of viruses in MS pathogenesis is indirect and limited, and an MS-specific virus infection has not been identified so far. Toxic models are highly useful to unravel mechanisms of de- and remyelination, but do not reflect other important aspects of MS pathology and pathogenesis. For all these reasons, it is important to select the right experimental model to answer specific questions in MS research.",2017 Oct 20,"['Lassmann, Hans', 'Bradl, Monika']",Acta Neuropathol,,,True
27966ec51b51b6fd67959b36c4a51300360865e4,PMC,"Novel roles of DC-SIGNR in colon cancer cell adhesion, migration, invasion, and liver metastasis",http://dx.doi.org/10.1186/s13045-016-0383-x,PMC5251210,28109307,CC BY,"BACKGROUND: Tumor metastasis is an essential cause of the poor prognosis of colon cancer. DC-SIGNR is a C-type lectin that is frequently found on human liver sinusoidal endothelial cells. LSECtin, which is a homologue of DC-SIGNR, has been demonstrated to participate in colon cancer liver metastasis. Due to the similarities in the expression pattern and structure of the two proteins, we speculated that DC-SIGNR could also be involved in this process. METHODS: Colon cancer cells were treated with the DC-SIGNR protein or control IgG, after which cell migration, invasion, and morphology were assayed. Xenograft mouse models were used to determine the role of DC-SIGNR in colon cancer liver metastasis in vivo. In addition, a human gene expression array was used to detect differential gene expression in colon cancer cells stimulated with the DC-SIGNR protein. The serum level of DC-SIGNR was examined in colon cancer patients by ELISA, and the significance of DC-SIGNR was determined. RESULTS: In our research, we investigated whether DC-SIGNR promotes colon cancer cell adhesion, migration, and invasion. Knocking down mouse DC-SIGNR decreased the liver metastatic potency of colon cancer cells and increased survival time. Expressing human DC-SIGNR enhanced colon cancer liver metastasis. Furthermore, DC-SIGNR conferred metastatic capability on cancer cells by upregulating various metallothionein isoforms. To validate the above results, we also found that the serum DC-SIGNR level was statistically higher in colon cancer patients with liver metastasis compared with those without metastasis. CONCLUSIONS: These results imply that DC-SIGNR may promote colon carcinoma hepatic metastasis and could serve as a promising therapeutic target for anticancer treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-016-0383-x) contains supplementary material, which is available to authorized users.",2017 Jan 21,"['Na, Heya', 'Liu, Xiaoli', 'Li, Xiaomeng', 'Zhang, Xinsheng', 'Wang, Yu', 'Wang, Zhaohui', 'Yuan, Menglang', 'Zhang, Yu', 'Ren, Shuangyi', 'Zuo, Yunfei']",J Hematol Oncol,,,True
85166a1c79d32bc2df2984260f1facc1a4d6148b,PMC,"Prevalence of avian infectious bronchitis virus in broiler chicken farms in south of Iraq, 2014 – 2015",,PMC5251354,28144423,CC BY,"Avian infectious bronchitis (IB), caused by a gammacoronavirus, is an OIE-listed (List B) disease and characterized by respiratory and renal involvements, causing high mortality, and economic loss in both layers and broilers. In comparison with other diagnostic methods, real-time polymerase chain reaction (RT-PCR) and conventional RT-PCR are potent, more sensitive and faster techniques for infectious bronchitis virus (IBV) detection. This research was conducted to detect IBV using specific primers of IB in three governorates (Basra, Thi-Qar and Muthana) in the south of Iraq. Tracheal specimens were collected from 46 IB suspected commercial broiler flocks. XCE2+ and XCE2- Primers, which amplify all IBV serotypes, were used. Primers MCE1+, BCE1+ and DCE1+ were used to amplify the specific nucleotide sequences of Massachusetts, 793/B and D274 genotypes, respectively. The results of real-time RT-PCR of this study showed that 34 (74.00%) out of 46 infected flocks were positive to IBV. The results of nested PCR showed that 50.00% and 5.89% of positive samples were belonged to genotypes 793/B and Massachusetts, respectively, and the remaining positive (44.11%) were unknown. The results indicate presence of Massachusetts and 793/B IBV strains in commercial broilers in southern Iraq.",2016 Dec 15 Autumn,"['Seger, Waleed', 'Ghalyanchi Langeroudi, Arash', 'Karimi, Vahid', 'Madadgar, Omid', 'Vasfi Marandi, Mehdi', 'Hashemzadeh, Masoud']",Vet Res Forum,,,True
f38ba8043876aa7abbefa69c26edc2aa3aaa4e94,PMC,"Detection of infectious bronchitis virus 793B, avian metapneumovirus, Mycoplasma gallisepticum and Mycoplasma synoviae in poultry in Ethiopia",http://dx.doi.org/10.1007/s11250-016-1195-2,PMC5253144,27924415,CC BY,"A survey was conducted into respiratory infectious diseases of poultry on a chicken breeder farm run by the Ethiopian Institute of Agricultural Research (EIAR), located in Debre Zeit, Ethiopia. Oropharyngeal swabs were collected from 117 randomly selected birds, and blood was taken from a subset of 73 of these birds. A combination of serological and molecular methods was used for detection of pathogens. For the first time in Ethiopia, we report the detection of variant infectious bronchitis virus (793B genotype), avian metapneumovirus subtype B and Mycoplasma synoviae in poultry. Mycoplasma gallisepticum was also found to be present; however, infectious laryngotracheitis virus was not detected by PCR. Newcastle disease virus (NDV) was not detected by PCR, but variable levels of anti-NDV HI antibody titres shows possible exposure to virulent strains or poor vaccine take, or both. For the burgeoning-intensive industry in Ethiopia, this study highlights several circulating infectious respiratory pathogens that can impact on poultry welfare and productivity.",2017 Dec 6,"['Hutton, S.', 'Bettridge, J.', 'Christley, R.', 'Habte, T.', 'Ganapathy, K.']",Trop Anim Health Prod,,,True
11d9deb4869385080d322af3026110247fb4d145,PMC,"Complete Genome Sequence of a Novel WU Polyomavirus Isolate from Arkansas, USA, Associated with Acute Respiratory Infection",http://dx.doi.org/10.1128/genomeA.01452-16,PMC5256223,28082496,CC BY,"We report here the complete genome sequence of a WU polyomavirus (WUPyV) isolate, also known as human polyomavirus 4, collected in 2016 from a patient in Arkansas with an acute respiratory infection. Isolate hPyV4/USA/AR001/2016 has a double-stranded DNA genome of 5,229 bp in length.",2017 Jan 12,"['Kennedy, J. L.', 'Denson, J. L.', 'Schwalm, K. S.', 'Stoner, A. N.', 'Kincaid, J. C.', 'Abramo, T. J.', 'Thompson, T. M.', 'Ulloa, E. M.', 'Burchiel, S. W.', 'Dinwiddie, D. L.']",Genome Announc,,,True
74eda2d826f50948657d096912bb32ccfbb17d0f,PMC,Operationalising resilience in longitudinal studies: a systematic review of methodological approaches,http://dx.doi.org/10.1136/jech-2015-206980,PMC5256275,27502781,CC BY,"Over the life course, we are invariably faced with some form of adversity. The process of positively adapting to adverse events is known as ‘resilience’. Despite the acknowledgement of 2 common components of resilience, that is, adversity and positive adaptation, no consensus operational definition has been agreed. Resilience operationalisations have been reviewed in a cross-sectional context; however, a review of longitudinal methods of operationalising resilience has not been conducted. The present study conducts a systematic review across Scopus and Web of Science capturing studies of ageing that posited operational definitions of resilience in longitudinal studies of ageing. Thirty-six studies met inclusion criteria. Non-acute events, for example, cancer, were the most common form of adversity identified and psychological components, for example, the absence of depression, the most common forms of positive adaptation. Of the included studies, 4 used psychometrically driven methods, that is, repeated administration of established resilience metrics, 9 used definition-driven methods, that is, a priori establishment of resilience components and criteria, and 23 used data-driven methods, that is, techniques that identify resilient individuals using latent variable models. Acknowledging the strengths and limitations of each operationalisation is integral to the appropriate application of these methods to life course and longitudinal resilience research.",2017 Jan 8,"['Cosco, T D', 'Kaushal, A', 'Hardy, R', 'Richards, M', 'Kuh, D', 'Stafford, M']",J Epidemiol Community Health,,,True
ebf5c3f42606a62d8bb4c03fa96623d0e2a56408,PMC,Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel,http://dx.doi.org/10.1371/journal.pone.0170592,PMC5256920,28114362,CC BY,"BACKGROUND: The number of pneumonia patients increased suddenly in Korean military hospitals in late December 2014, indicating the urgent need for an epidemic outbreak investigation. METHODS: We conducted a prospective study of pneumonia etiology among immunocompetent young adults admitted to Daejeon Armed Forces hospital. Patient blood and sputum samples were subjected to conventional culture, serology, and polymerase chain reaction tests for respiratory viruses and atypical pathogens. RESULTS: From January to May 2015, we enrolled 191 (189 male) adults with pneumonia; the mean age was 20.1 ± 1.3 years. Five patients had severe pneumonia, and one died. Pathogenic human adenoviruses were most common (HAdV, 153/191 [80.1%]), indicating a HAdV pneumonia outbreak. Genotyping of 35 isolates indicated that 34 matched HAdV-55 and one matched HAdV-2. HAdV pneumonia infected recruit trainees most frequently. High and prolonged fever, nasal congestion, sore throat, and pharyngeal inflammation were significantly more common in the HAdV pneumonia group, compared to patients with other or unknown causes of pneumonia. Only 12% of HAdV pneumonia patients displayed leukocytosis, whereas febrile leukopenia (62.7%) and thrombocytopenia (41%) were commonly observed. HAdV pneumonia patient chest CT scans displayed ground glass opacity (with or without septal thickness) with consolidation in 50.0% of patients. CONCLUSIONS: An outbreak of HAdV respiratory infection occurred at the Korean military training center. HAdV pneumonia exhibited specific laboratory and clinical features, and although most patients were cured without complication, some progressed to respiratory failure and fatality. Therefore, HAdV vaccine should be provided to military trainees in Korea.",2017 Jan 23,"['Park, Ji Young', 'Kim, Bong-Joon', 'Lee, Eun Jung', 'Park, Kwi Sung', 'Park, Hee Sun', 'Jung, Sung Soo', 'Kim, Ju Ock']",PLoS One,,,True
62641fdbeeff7b487788b42b59a3d1ca66bdb978,PMC,Selective inhibition of Ebola entry with selective estrogen receptor modulators by disrupting the endolysosomal calcium,http://dx.doi.org/10.1038/srep41226,PMC5259750,28117364,CC BY,"The Ebola crisis occurred in West-Africa highlights the urgency for its clinical treatments. Currently, no Food and Drug Administration (FDA)-approved therapeutics are available. Several FDA-approved drugs, including selective estrogen receptor modulators (SERMs), possess selective anti-Ebola activities. However, the inhibitory mechanisms of these drugs remain elusive. By analyzing the structures of SERMs and their incidental biological activity (cholesterol accumulation), we hypothesized that this incidental biological activity induced by SERMs could be a plausible mechanism as to their inhibitory effects on Ebola infection. Herein, we demonstrated that the same dosages of SERMs which induced cholesterol accumulation also inhibited Ebola infection. SERMs reduced the cellular sphingosine and subsequently caused endolysosomal calcium accumulation, which in turn led to blocking the Ebola entry. Our study clarified the specific anti-Ebola mechanism of SERMs, even the cationic amphiphilic drugs (CADs), this mechanism led to the endolysosomal calcium as a critical target for development of anti-Ebola drugs.",2017 Jan 24,"['Fan, Hanlu', 'Du, Xiaohong', 'Zhang, Jingyuan', 'Zheng, Han', 'Lu, Xiaohui', 'Wu, Qihui', 'Li, Haifeng', 'Wang, Han', 'Shi, Yi', 'Gao, George', 'Zhou, Zhuan', 'Tan, Dun-Xian', 'Li, Xiangdong']",Sci Rep,,,True
d8454139f839889cb542b3c91009e20ceded8625,PMC,xMAP Technology: Applications in Detection of Pathogens,http://dx.doi.org/10.3389/fmicb.2017.00055,PMC5263158,28179899,CC BY,"xMAP technology is applicable for high-throughput, multiplex and simultaneous detection of different analytes within a single complex sample. xMAP multiplex assays are currently available in various nucleic acid and immunoassay formats, enabling simultaneous detection and typing of pathogenic viruses, bacteria, parasites and fungi and also antigen or antibody interception. As an open architecture platform, the xMAP technology is beneficial to end users and therefore it is used in various pharmaceutical, clinical and research laboratories. The main aim of this review is to summarize the latest findings and applications in the field of pathogen detection using microsphere-based multiplex assays.",2017 Jan 25,"['Reslova, Nikol', 'Michna, Veronika', 'Kasny, Martin', 'Mikel, Pavel', 'Kralik, Petr']",Front Microbiol,,,True
26401aab640b61b28b31696b3540662e5e1428d8,PMC,Risk of travel-related cases of Zika virus infection is predicted by transmission intensity in outbreak-affected countries,http://dx.doi.org/10.1186/s13071-017-1977-z,PMC5264286,28122631,CC BY,"BACKGROUND: Zika virus (ZIKV) infection is emerging globally, currently causing outbreaks in the Caribbean, and Central and South America, and putting travellers to affected countries at risk. Model-based estimates for the basic reproduction number (R (0)) of ZIKV in affected Caribbean and Central and South American countries, obtained from 2015 to 2016 human case surveillance data, were compared by logistic regression and Receiver-Operating Characteristic (ROC), with the prevalence of ZIKV-positive test results in Canadians who travelled to them. RESULTS: Estimates of R (0) for each country were a good predictor of the ZIKV test result (ROC area under the curve = 0.83) and the odds of testing positive was 11-fold greater for travellers visiting countries with estimated R (0) ≥ 2.76, compared to those visiting countries with R (0) < 2.76. CONCLUSIONS: Risk to travellers varies widely amongst countries affected by ZIKV outbreaks. Estimates of R (0) from surveillance data can assist in assessing levels of risk for travellers and may help improve travel advice. They may also allow better prediction of spread of ZIKV from affected countries by travellers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-017-1977-z) contains supplementary material, which is available to authorized users.",2017 Jan 25,"['Ogden, Nicholas H.', 'Fazil, Aamir', 'Safronetz, David', 'Drebot, Michael A.', 'Wallace, Justine', 'Rees, Erin E.', 'Decock, Kristina', 'Ng, Victoria']",Parasit Vectors,,,True
a7da39018f8bac38c77086632a5ab80e8fe73516,PMC,Evaluation of TaqMan qPCR System Integrating Two Identically Labelled Hydrolysis Probes in Single Assay,http://dx.doi.org/10.1038/srep41392,PMC5264587,28120891,CC BY,"Ongoing evolution of viral pathogens is a significant issue in diagnostic virology employing TaqMan qPCR/RT-qPCR. Specific concerns are related to false negativity due to probe binding failure. One option for compensating for such deficiency is to integrate a second identically labelled probe in the assay. However, how this alteration influences the reaction parameters has not been comprehensively demonstrated. In the present study, we evaluate a TaqMan protocol using two identically labelled hydrolysis probes (simple, LNA (locked-nucleic-acid)) and MGB (minor-groove-binder) modified probes and combinations thereof in a single assay. Our results based on a synthetic amplicon suggest that the second probe does not compromise the TaqMan qPCR/RT-qPCR parameters, which repeatedly and reproducibly remained comparable to those of the corresponding single-probe assays, irrespective of the relative probe orientation, whether opposite or tandem, and probe modifications or combinations thereof. On the other hand, the second probe additively contributed to the overall fluorescence signal. The utility of the dual-probe approach was demonstrated on practical examples by using field specimens. We hope that the present study might serve as a theoretical basis for the development or improvement of TaqMan qPCR/RT-qPCR assays for the detection of highly variable nucleic acid templates.",2017 Jan 25,"['Nagy, Alexander', 'Vitásková, Eliška', 'Černíková, Lenka', 'Křivda, Vlastimil', 'Jiřincová, Helena', 'Sedlák, Kamil', 'Horníčková, Jitka', 'Havlíčková, Martina']",Sci Rep,,,True
3155a364ad32ea7fa1876d8e639c067023b572dd,PMC,Evaluation of TaqMan qPCR System Integrating Two Identically Labelled Hydrolysis Probes in Single Assay,http://dx.doi.org/10.1038/srep41392,PMC5264587,28120891,CC BY,"Ongoing evolution of viral pathogens is a significant issue in diagnostic virology employing TaqMan qPCR/RT-qPCR. Specific concerns are related to false negativity due to probe binding failure. One option for compensating for such deficiency is to integrate a second identically labelled probe in the assay. However, how this alteration influences the reaction parameters has not been comprehensively demonstrated. In the present study, we evaluate a TaqMan protocol using two identically labelled hydrolysis probes (simple, LNA (locked-nucleic-acid)) and MGB (minor-groove-binder) modified probes and combinations thereof in a single assay. Our results based on a synthetic amplicon suggest that the second probe does not compromise the TaqMan qPCR/RT-qPCR parameters, which repeatedly and reproducibly remained comparable to those of the corresponding single-probe assays, irrespective of the relative probe orientation, whether opposite or tandem, and probe modifications or combinations thereof. On the other hand, the second probe additively contributed to the overall fluorescence signal. The utility of the dual-probe approach was demonstrated on practical examples by using field specimens. We hope that the present study might serve as a theoretical basis for the development or improvement of TaqMan qPCR/RT-qPCR assays for the detection of highly variable nucleic acid templates.",2017 Jan 25,"['Nagy, Alexander', 'Vitásková, Eliška', 'Černíková, Lenka', 'Křivda, Vlastimil', 'Jiřincová, Helena', 'Sedlák, Kamil', 'Horníčková, Jitka', 'Havlíčková, Martina']",Sci Rep,,,False
f6c72b0d5522ce852bc2aeb711ab57fb75b3489a,PMC,Spiroplasma eriocheiris Adhesin-Like Protein (ALP) Interacts with Epidermal Growth Factor (EGF) Domain Proteins to Facilitate Infection,http://dx.doi.org/10.3389/fcimb.2017.00013,PMC5266718,28184355,CC BY,"Spiroplasma eriocheiris is a novel pathogen found in recent years, causing the tremor disease (TD) of Chinese mitten crab Eriocheir sinensis. Like Spiroplasma mirum, S. eriocheiris infects the newborn mouse (adult mice are not infected) and can cause cataract. Adhesion-related protein is an important protein involved in the interaction between pathogen and host. In this study, the Adhesin-like Protein (ALP) of S. eriocheiris was detected on its outer membrane by using immune electron microscopy, and was found to be involved in the bacterium's infection of mouse embryo fibroblasts (3T6-Swiss albino). Yeast two-hybrid analysis demonstrated that ALP interacts with a diverse group of mouse proteins. The interactions between recombinant partial fibulin7 (FBLN7; including two epidermal growth factor [EGF] domains) and ALP were confirmed by Far-western blotting and colocalization. We synthetized the domains of FBLN7 [EGF domain: amino acids 136–172 and complement control protein (CCP) domain: 81–134 amino acids], and demonstrated that only EGF domain of FBLN7 can interact with ALP. Because the EGF domain has high degree of similarity to EGF, it can activate the downstream EGFR signaling pathway, in key site amino acids. The EGFR pathway in 3T6 cells was restrained after rALP stimulation resulting from competitive binding of ALP to EGF. The unborn mouse, newborn mouse, and the adult mouse with cataract have a small amount of expressed FBLN7; however, none was detected in the brain and very little expression was seen in the eye of normal adult mice. In short, ALP as a S. eriocheiris surface protein, is critical for infection and further supports the role of ALP in S. eriocheiris infection by competitive effection of the EGF/EGFR axis of the target cells.",2017 Jan 26,"['Hou, Libo', 'Liu, Yuhan', 'Gao, Qi', 'Xu, Xuechuan', 'Ning, Mingxiao', 'Bi, Jingxiu', 'Liu, Hui', 'Liu, Min', 'Gu, Wei', 'Wang, Wen', 'Meng, Qingguo']",Front Cell Infect Microbiol,,,True
b516e53a03a6dc4df9eb13c85d0a57ef71452125,PMC,A protocol for a systematic literature review: comparing the impact of seasonal and meteorological parameters on acute respiratory infections in Indigenous and non-Indigenous peoples,http://dx.doi.org/10.1186/s13643-016-0399-x,PMC5267362,28122603,CC BY,"BACKGROUND: Acute respiratory infections (ARI) are a leading cause of morbidity and mortality globally, and are often linked to seasonal and/or meteorological conditions. Globally, Indigenous peoples may experience a different burden of ARI compared to non-Indigenous peoples. This protocol outlines our process for conducting a systematic review to investigate whether associations between ARI and seasonal or meteorological parameters differ between Indigenous and non-Indigenous groups residing in the same geographical region. METHODOLOGY: A search string will be used to search PubMed(®), CAB Abstracts/CAB Direct(©), and Science Citation Index(®) aggregator databases. Articles will be screened using inclusion/exclusion criteria applied first at the title and abstract level, and then at the full article level by two independent reviewers. Articles maintained after full article screening will undergo risk of bias assessment and data will be extracted. Heterogeneity tests, meta-analysis, and forest and funnel plots will be used to synthesize the results of eligible studies. DISCUSSION AND REGISTRATION: This protocol paper describes our systematic review methods to identify and analyze relevant ARI, season, and meteorological literature with robust reporting. The results are intended to improve our understanding of potential associations between seasonal and meteorological parameters and ARI and, if identified, whether this association varies by place, population, or other characteristics. The protocol is registered in the PROSPERO database (#38051). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13643-016-0399-x) contains supplementary material, which is available to authorized users.",2017 Jan 26,"['Bishop-Williams, Katherine E.', 'Sargeant, Jan M.', 'Berrang-Ford, Lea', 'Edge, Victoria L.', 'Cunsolo, Ashlee', 'Harper, Sherilee L.']",Syst Rev,,,True
ce6f81a5f2e09ff7a23ea939e3c3c062ef6130c7,PMC,Costs of care at the end of life among elderly patients with chronic kidney disease: patterns and predictors in a nationwide cohort study,http://dx.doi.org/10.1186/s12882-017-0456-2,PMC5267416,28122500,CC BY,"BACKGROUND: Despite the urgent need for evidence to guide the end-of-life (EOL) care for patients with chronic kidney disease (CKD), we have limited knowledge of the costs and intensity of EOL care in this population. The present study examined patterns and predictors for EOL care intensity among elderly patients with CKD. METHODS: We conducted a retrospective nationwide cohort study utilizing the Taiwan National Health Insurance (NHI) Research Database. A total of 65,124 CKD patients aged ≥ 60 years, who died in hospitals or shortly after discharge between 2002 and 2012 were analyzed. The primary outcomes were inpatient expenses and use of surgical interventions in the last 30 days of life. Utilization of intensive care unit (ICU), mechanical ventilation, resuscitation, and dialysis was also examined in a sub-sample of 2072 patients with detailed prescription data. Multivariate log-linear and logistic regression analyses were performed to assess patient-, physician-, and facility-specific predictors and the potential impact of a 2009 payment policy to reimburse hospice care for non-cancer patients. RESULTS: During the last 30 days of life, average inpatients costs for elderly CKD patients were approximately US$10,260, with 40.9% receiving surgical interventions, 40.2% experiencing ICU admission, 45.3% undergoing mechanical ventilation, 14.7% receiving resuscitation and 42.0% receiving dialysis. Significant variability was observed in the inpatient costs and use of intensive services. Costs were lower among individuals with the following characteristics: advanced age; high income; high Charlson Comorbidity Index scores; treatment by older physicians, nephrologists, and family medicine physicians; and treatment at local hospitals. Similar findings were obtained for the use of surgical interventions and other intensive services. A declining trend was detected in the costs of EOL care, use of surgical interventions and resuscitation between 2009 and 2012, which is consistent with the impact of a 2009 NHI payment policy to reimburse non-cancer hospice care. CONCLUSIONS: Overall EOL costs and rates of intensive service use among older patients with CKD were high, with significant variability across various patient and provider characteristics. Several opportunities exist for providers and policy makers to reduce costs and enhance the value of EOL care for this population.",2017 Jan 26,"['Chen, Bradley', 'Fan, Victoria Y.', 'Chou, Yiing-Jenq', 'Kuo, Chin-Chi']",BMC Nephrol,,,True
977007f901c5697f613ad1b475532ebaf7baef86,PMC,Molecular Mimicry between Chikungunya Virus and Host Components: A Possible Mechanism for the Arthritic Manifestations,http://dx.doi.org/10.1371/journal.pntd.0005238,PMC5268390,28125580,CC BY,"BACKGROUND: Chikungunya virus (CHIKV), a reemerging pathogen causes a self limited illness characterized by fever, headache, myalgia and arthralgia. However, 10–20% affected individuals develop persistent arthralgia which contributes to considerable morbidity. The exact molecular mechanisms underlying these manifestations are not well understood. The present study investigated the possible occurrence of molecular mimicry between CHIKV E1 glycoprotein and host human components. METHODOLOGY: Bioinformatic tools were used to identify peptides of CHIKV E1 exhibiting similarity to host components. Two peptides (A&B) were identified using several bioinformatic tools, synthesised and used to validate the results obtained in silico. An ELISA was designed to assess the immunoreactivity of serum samples from CHIKV patients to these peptides. Further, experiments were conducted in a C57BL/6J experimental mouse model to investigate if peptide A and peptide B were indeed capable of inducing pathology. FINDINGS: The serum samples showed reactivity of varying degrees, indicating that these peptides are indeed being recognized by the host immune system during CHIKV infection. Further, these peptides when injected into C57BL/6J mice were able to induce significant inflammation in the muscles of C57BL/6J mice, similar to that observed in animals that were injected with CHIKV alone. Additionally, animals that were primed initially with CHIKV followed by a subsequent injection of the CHIKV peptides exhibited enhanced inflammatory pathology in the skeletal muscles as compared to animals that were injected with peptides or virus alone. Collectively these observations validate the hypothesis that molecular mimicry between CHIKV E1 protein and host proteins does contribute to pathology in CHIKV infection.",2017 Jan 26,"['Reddy, Vijayalakshmi', 'Desai, Anita', 'Krishna, Shankar Susarla', 'Vasanthapuram, Ravi']",PLoS Negl Trop Dis,,,True
74faecf00d9247bc088c0cb084f69b2135062fe8,PMC,Biospecimen Repositories and Integrated Databases as Critical Infrastructure for Pathogen Discovery and Pathobiology Research,http://dx.doi.org/10.1371/journal.pntd.0005133,PMC5268418,28125619,CC0,,2017 Jan 26,"['Dunnum, Jonathan L.', 'Yanagihara, Richard', 'Johnson, Karl M.', 'Armien, Blas', 'Batsaikhan, Nyamsuren', 'Morgan, Laura', 'Cook, Joseph A.']",PLoS Negl Trop Dis,,,True
59f96c4166966aa929450a859c3d3fb2b6058c50,PMC,Genotyping of human rhinovirus in adult patients with acute respiratory infections identified predominant infections of genotype A21,http://dx.doi.org/10.1038/srep41601,PMC5269714,28128353,CC BY,"Human rhinovirus (HRV) is an important causative agent of acute respiratory tract infections (ARTIs). The roles of specific HRV genotypes in patients suffering from ARTIs have not been well established. We recruited 147 adult inpatients with community-acquired pneumonia (CAP) and 291 adult outpatients with upper ARTIs (URTIs). Respiratory pathogens were screened via PCR assays. HRV was detected in 42 patients, with 35 species A, five B and two C. Seventeen genotypes were identified, and HRV-A21 ranked the highest (9/42, 21.4%). The HRV-A21-positive infections were detected in four patients with CAP and in five with URTIs, all without co-infections. The HRV-A21 genome sequenced in this study contained 12 novel coding polymorphisms in viral protein (VP) 1, VP2 EF loop, VP3 knob and 3D regions. The infections of HRV-A21 virus obtained in this study could not be neutralized by antiserum of HRV-A21 prototype strain (VR-1131), indicating remarkable antigenic variation. Metagenomic analysis showed the HRV-A21 reads were dominant in bronchoalveolar lavage fluid of the three HRV-A21-positive patients with severe CAP, in which two dead. Our results highlight an unexpected infection of genotype HRV-A21 in the clinic, indicating the necessity of precise genotyping and surveillance of HRVs to improve the clinical management of ARTIs.",2017 Jan 27,"['Ren, Lili', 'Yang, Donghong', 'Ren, Xianwen', 'Li, Mingkun', 'Mu, Xinlin', 'Wang, Qi', 'Cao, Jie', 'Hu, Ke', 'Yan, Chunliang', 'Fan, Hongwei', 'Li, Xiangxin', 'Chen, Yusheng', 'Wang, Ruiqin', 'An, Fucheng', 'An, Shuchang', 'Luo, Ming', 'Wang, Ying', 'Xiao, Yan', 'Xiang, Zichun', 'Xiao, Yan', 'Li, Li', 'Huang, Fang', 'Jin, Qi', 'Gao, Zhancheng', 'Wang, Jianwei']",Sci Rep,,,True
22faab96b423cab9df3cd453727e6a7763de4bb6,PMC,Assessment of the Usefulness of Multiplex Real-Time PCR Tests in the Diagnostic and Therapeutic Process of Pneumonia in Hospitalized Children: A Single-Center Experience,http://dx.doi.org/10.1155/2017/8037963,PMC5274672,28182108,CC BY,"The aim of the study was assessment of the usefulness of multiplex real-time PCR tests in the diagnostic and therapeutic process in children hospitalized due to pneumonia and burdened with comorbidities. Methods. The study group included 97 children hospitalized due to pneumonia at the Karol Jonscher Teaching Hospital in Poznań, in whom multiplex real-time PCR tests (FTD respiratory pathogens 33; fast-track diagnostics) were used. Results. Positive test results of the test were achieved in 74 patients (76.3%). The average age in the group was 56 months. Viruses were detected in 61 samples (82% of all positive results); bacterial factors were found in 29 samples (39% of all positive results). The presence of comorbidities was established in 90 children (92.78%). On the basis of the obtained results, 5 groups of patients were established: viral etiology of infection, 34 patients; bacterial etiology, 7 patients; mixed etiology, 23 patients; pneumocystis, 9 patients; and no etiology diagnosed, 24 patients. Conclusions. Our analysis demonstrated that the participation of viruses in causing severe lung infections is significant in children with comorbidities. Multiplex real-time PCR tests proved to be more useful in establishing the etiology of pneumonia in hospitalized children than the traditional microbiological examinations.",2017 Jan 15,"['Gowin, Ewelina', 'Bartkowska-Śniatkowska, Alicja', 'Jończyk-Potoczna, Katarzyna', 'Wysocka-Leszczyńska, Joanna', 'Bobkowski, Waldemar', 'Fichna, Piotr', 'Sobkowiak, Paulina', 'Mazur-Melewska, Katarzyna', 'Bręborowicz, Anna', 'Wysocki, Jacek', 'Januszkiewicz-Lewandowska, Danuta']",Biomed Res Int,,,True
7d286a7255cf820dba6ea89a13764045161ddbea,PMC,Oligomerization domains in the glycan‐binding receptors DC‐SIGN and DC‐SIGNR: Sequence variation and stability differences,http://dx.doi.org/10.1002/pro.3083,PMC5275740,27859859,CC BY,"Human dendritic cell‐specific intercellular adhesion molecule‐1 grabbing nonintegrin, DC‐SIGN, and the sinusoidal endothelial cell receptor DC‐SIGNR or L‐SIGN, are closely related sugar‐binding receptors. DC‐SIGN acts both as a pathogen‐binding endocytic receptor and as a cell adhesion molecule, while DC‐SIGNR has only the pathogen‐binding function. In addition to differences in the sugar‐binding properties of the carbohydrate‐recognition domains in the two receptors, there are sequence differences in the adjacent neck domains, which are coiled‐coil tetramerization domains comprised largely of 23‐amino acid repeat units. A series of model polypeptides consisting of uniform repeat units have been characterized by gel filtration, differential scanning calorimetry and circular dichroism. The results demonstrate that two features characterize repeat units which form more stable tetramers: a leucine reside in the first position of the heptad pattern of hydrophobic residues that pack on the inside of the coiled coil and an arginine residue on the surface of the coiled coil that forms a salt bridge with a glutamic acid residue in the same polypeptide chain. In DC‐SIGNR from all primates, very stable repeat units predominate, so the carbohydrate‐recognition domains must be held relatively closely together. In contrast, stable repeat units are found only near the membrane in DC‐SIGN. The presence of residues that disrupt tetramer formation in repeat units near the carbohydrate‐recognition domains of DC‐SIGN would allow these domains to splay further apart. Thus, the neck domains of DC‐SIGN and DC‐SIGNR can contribute to the different functions of these receptors by presenting the sugar‐binding sites in different contexts.",2017 Feb 22,"['dos Santos, Ália', 'Hadjivasiliou, Andreas', 'Ossa, Felipe', 'Lim, Novandy K.', 'Turgut, Aylin', 'Taylor, Maureen E.', 'Drickamer, Kurt']",Protein Sci,,,True
9e7bb369224888a04493301fe9b7e1d4e31531c1,PMC,Inference of Transmission Network Structure from HIV Phylogenetic Trees,http://dx.doi.org/10.1371/journal.pcbi.1005316,PMC5279806,28085876,CC0,"Phylogenetic inference is an attractive means to reconstruct transmission histories and epidemics. However, there is not a perfect correspondence between transmission history and virus phylogeny. Both node height and topological differences may occur, depending on the interaction between within-host evolutionary dynamics and between-host transmission patterns. To investigate these interactions, we added a within-host evolutionary model in epidemiological simulations and examined if the resulting phylogeny could recover different types of contact networks. To further improve realism, we also introduced patient-specific differences in infectivity across disease stages, and on the epidemic level we considered incomplete sampling and the age of the epidemic. Second, we implemented an inference method based on approximate Bayesian computation (ABC) to discriminate among three well-studied network models and jointly estimate both network parameters and key epidemiological quantities such as the infection rate. Our ABC framework used both topological and distance-based tree statistics for comparison between simulated and observed trees. Overall, our simulations showed that a virus time-scaled phylogeny (genealogy) may be substantially different from the between-host transmission tree. This has important implications for the interpretation of what a phylogeny reveals about the underlying epidemic contact network. In particular, we found that while the within-host evolutionary process obscures the transmission tree, the diversification process and infectivity dynamics also add discriminatory power to differentiate between different types of contact networks. We also found that the possibility to differentiate contact networks depends on how far an epidemic has progressed, where distance-based tree statistics have more power early in an epidemic. Finally, we applied our ABC inference on two different outbreaks from the Swedish HIV-1 epidemic.",2017 Jan 13,"['Giardina, Federica', 'Romero-Severson, Ethan Obie', 'Albert, Jan', 'Britton, Tom', 'Leitner, Thomas']",PLoS Comput Biol,,,True
79ffb79aefdb0400628fbe8dbbf012ff168129a1,PMC,Inference of Transmission Network Structure from HIV Phylogenetic Trees,http://dx.doi.org/10.1371/journal.pcbi.1005316,PMC5279806,28085876,CC0,"Phylogenetic inference is an attractive means to reconstruct transmission histories and epidemics. However, there is not a perfect correspondence between transmission history and virus phylogeny. Both node height and topological differences may occur, depending on the interaction between within-host evolutionary dynamics and between-host transmission patterns. To investigate these interactions, we added a within-host evolutionary model in epidemiological simulations and examined if the resulting phylogeny could recover different types of contact networks. To further improve realism, we also introduced patient-specific differences in infectivity across disease stages, and on the epidemic level we considered incomplete sampling and the age of the epidemic. Second, we implemented an inference method based on approximate Bayesian computation (ABC) to discriminate among three well-studied network models and jointly estimate both network parameters and key epidemiological quantities such as the infection rate. Our ABC framework used both topological and distance-based tree statistics for comparison between simulated and observed trees. Overall, our simulations showed that a virus time-scaled phylogeny (genealogy) may be substantially different from the between-host transmission tree. This has important implications for the interpretation of what a phylogeny reveals about the underlying epidemic contact network. In particular, we found that while the within-host evolutionary process obscures the transmission tree, the diversification process and infectivity dynamics also add discriminatory power to differentiate between different types of contact networks. We also found that the possibility to differentiate contact networks depends on how far an epidemic has progressed, where distance-based tree statistics have more power early in an epidemic. Finally, we applied our ABC inference on two different outbreaks from the Swedish HIV-1 epidemic.",2017 Jan 13,"['Giardina, Federica', 'Romero-Severson, Ethan Obie', 'Albert, Jan', 'Britton, Tom', 'Leitner, Thomas']",PLoS Comput Biol,,,False
472602b70bca7504518686f34f5b1b15dbe21725,PMC,Inference of Transmission Network Structure from HIV Phylogenetic Trees,http://dx.doi.org/10.1371/journal.pcbi.1005316,PMC5279806,28085876,CC0,"Phylogenetic inference is an attractive means to reconstruct transmission histories and epidemics. However, there is not a perfect correspondence between transmission history and virus phylogeny. Both node height and topological differences may occur, depending on the interaction between within-host evolutionary dynamics and between-host transmission patterns. To investigate these interactions, we added a within-host evolutionary model in epidemiological simulations and examined if the resulting phylogeny could recover different types of contact networks. To further improve realism, we also introduced patient-specific differences in infectivity across disease stages, and on the epidemic level we considered incomplete sampling and the age of the epidemic. Second, we implemented an inference method based on approximate Bayesian computation (ABC) to discriminate among three well-studied network models and jointly estimate both network parameters and key epidemiological quantities such as the infection rate. Our ABC framework used both topological and distance-based tree statistics for comparison between simulated and observed trees. Overall, our simulations showed that a virus time-scaled phylogeny (genealogy) may be substantially different from the between-host transmission tree. This has important implications for the interpretation of what a phylogeny reveals about the underlying epidemic contact network. In particular, we found that while the within-host evolutionary process obscures the transmission tree, the diversification process and infectivity dynamics also add discriminatory power to differentiate between different types of contact networks. We also found that the possibility to differentiate contact networks depends on how far an epidemic has progressed, where distance-based tree statistics have more power early in an epidemic. Finally, we applied our ABC inference on two different outbreaks from the Swedish HIV-1 epidemic.",2017 Jan 13,"['Giardina, Federica', 'Romero-Severson, Ethan Obie', 'Albert, Jan', 'Britton, Tom', 'Leitner, Thomas']",PLoS Comput Biol,,,True
1e9b7f2dccef9beb4b57488aeb420bbe3ecff436,PMC,Inference of Transmission Network Structure from HIV Phylogenetic Trees,http://dx.doi.org/10.1371/journal.pcbi.1005316,PMC5279806,28085876,CC0,"Phylogenetic inference is an attractive means to reconstruct transmission histories and epidemics. However, there is not a perfect correspondence between transmission history and virus phylogeny. Both node height and topological differences may occur, depending on the interaction between within-host evolutionary dynamics and between-host transmission patterns. To investigate these interactions, we added a within-host evolutionary model in epidemiological simulations and examined if the resulting phylogeny could recover different types of contact networks. To further improve realism, we also introduced patient-specific differences in infectivity across disease stages, and on the epidemic level we considered incomplete sampling and the age of the epidemic. Second, we implemented an inference method based on approximate Bayesian computation (ABC) to discriminate among three well-studied network models and jointly estimate both network parameters and key epidemiological quantities such as the infection rate. Our ABC framework used both topological and distance-based tree statistics for comparison between simulated and observed trees. Overall, our simulations showed that a virus time-scaled phylogeny (genealogy) may be substantially different from the between-host transmission tree. This has important implications for the interpretation of what a phylogeny reveals about the underlying epidemic contact network. In particular, we found that while the within-host evolutionary process obscures the transmission tree, the diversification process and infectivity dynamics also add discriminatory power to differentiate between different types of contact networks. We also found that the possibility to differentiate contact networks depends on how far an epidemic has progressed, where distance-based tree statistics have more power early in an epidemic. Finally, we applied our ABC inference on two different outbreaks from the Swedish HIV-1 epidemic.",2017 Jan 13,"['Giardina, Federica', 'Romero-Severson, Ethan Obie', 'Albert, Jan', 'Britton, Tom', 'Leitner, Thomas']",PLoS Comput Biol,,,False
61a3e6188ff0e2fcbb6667aea8550b2bf0318d35,PMC,Drosophila CG3303 is an essential endoribonuclease linked to TDP-43-mediated neurodegeneration,http://dx.doi.org/10.1038/srep41559,PMC5282483,28139767,CC BY,"Endoribonucleases participate in almost every step of eukaryotic RNA metabolism, acting either as degradative or biosynthetic enzymes. We previously identified the founding member of the Eukaryotic EndoU ribonuclease family, whose components display unique biochemical features and are flexibly involved in important biological processes, such as ribosome biogenesis, tumorigenesis and viral replication. Here we report the discovery of the CG3303 gene product, which we named DendoU, as a novel family member in Drosophila. Functional characterisation revealed that DendoU is essential for Drosophila viability and nervous system activity. Pan-neuronal silencing of dendoU resulted in fly immature phenotypes, highly reduced lifespan and dramatic motor performance defects. Neuron-subtype selective silencing showed that DendoU is particularly important in cholinergic circuits. At the molecular level, we unveiled that DendoU is a positive regulator of the neurodegeneration-associated protein dTDP-43, whose downregulation recapitulates the ensemble of dendoU-dependent phenotypes. This interdisciplinary work, which comprehends in silico, in vitro and in vivo studies, unveils a relevant role for DendoU in Drosophila nervous system physio-pathology and highlights that DendoU-mediated neurotoxicity is, at least in part, contributed by dTDP-43 loss-of-function.",2017 Jan 31,"['Laneve, Pietro', 'Piacentini, Lucia', 'Casale, Assunta Maria', 'Capauto, Davide', 'Gioia, Ubaldo', 'Cappucci, Ugo', 'Di Carlo, Valerio', 'Bozzoni, Irene', 'Di Micco, Patrizio', 'Morea, Veronica', 'Di Franco, Carmela Antonia', 'Caffarelli, Elisa']",Sci Rep,,,True
934b84825155ad6e75113e6d85eeab0a07f97ff4,PMC,Drosophila CG3303 is an essential endoribonuclease linked to TDP-43-mediated neurodegeneration,http://dx.doi.org/10.1038/srep41559,PMC5282483,28139767,CC BY,"Endoribonucleases participate in almost every step of eukaryotic RNA metabolism, acting either as degradative or biosynthetic enzymes. We previously identified the founding member of the Eukaryotic EndoU ribonuclease family, whose components display unique biochemical features and are flexibly involved in important biological processes, such as ribosome biogenesis, tumorigenesis and viral replication. Here we report the discovery of the CG3303 gene product, which we named DendoU, as a novel family member in Drosophila. Functional characterisation revealed that DendoU is essential for Drosophila viability and nervous system activity. Pan-neuronal silencing of dendoU resulted in fly immature phenotypes, highly reduced lifespan and dramatic motor performance defects. Neuron-subtype selective silencing showed that DendoU is particularly important in cholinergic circuits. At the molecular level, we unveiled that DendoU is a positive regulator of the neurodegeneration-associated protein dTDP-43, whose downregulation recapitulates the ensemble of dendoU-dependent phenotypes. This interdisciplinary work, which comprehends in silico, in vitro and in vivo studies, unveils a relevant role for DendoU in Drosophila nervous system physio-pathology and highlights that DendoU-mediated neurotoxicity is, at least in part, contributed by dTDP-43 loss-of-function.",2017 Jan 31,"['Laneve, Pietro', 'Piacentini, Lucia', 'Casale, Assunta Maria', 'Capauto, Davide', 'Gioia, Ubaldo', 'Cappucci, Ugo', 'Di Carlo, Valerio', 'Bozzoni, Irene', 'Di Micco, Patrizio', 'Morea, Veronica', 'Di Franco, Carmela Antonia', 'Caffarelli, Elisa']",Sci Rep,,,False
b35188139844b656464c0727fa39ec03d970c443,PMC,"Mx1, OAS1 and OAS2 polymorphisms are associated with the severity of liver disease in HIV/HCV-coinfected patients: A cross-sectional study",http://dx.doi.org/10.1038/srep41516,PMC5282518,28139728,CC BY,"The mechanisms involved in the chronic hepatitis C progression are incompletely understood. The aim was to analyze the association between 2′5′oligoadenylate synthetase 1,2 and 3 (OAS1-3) and myxovirus resistance proteins 1 (Mx1) polymorphisms and severity of liver disease in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients. We performed a cross-sectional study in 219 patients that underwent a liver biopsy. DNA genotyping for Mx1 (rs469390), OAS1 (rs2285934), OAS2 (rs1293762) and OAS3 (rs2010604) was performed by using GoldenGate assay. The outcome variables ion liver biopsy were: (i) significant fibrosis (F ≥ 2); (ii) moderate activity grade (A ≥ 2). Additive model of inheritance for genetic association test was used. The likelihood of having significant fibrosis (F ≥ 2) was lower in patients carrying OAS2 rs1293762 A allele [adjusted odds ratio (aOR) = 0.51; p = 0.040]. Besides, the likelihood of having moderate activity grade (A ≥ 2) was higher in patients carrying Mx1 rs464397 C allele (aOR = 1.63; p = 0.028) and Mx1 rs469390 G allele (aOR = 1.97; p = 0.005), while it was lower in patients carrying OAS1 rs2285934 A allele (aOR = 0.64; p = 0.039) and OAS2 rs1293762 A allele (aOR = 0.41; p = 0.009). In conclusion, Mx1 and OAS1-2 polymorphisms were associated with the severity of liver disease in HIV/HCV-coinfected patients, suggesting a significant role in the progression of hepatic fibrosis.",2017 Jan 31,"['García-Álvarez, Mónica', 'Berenguer, Juan', 'Jiménez-Sousa, María A.', 'Pineda-Tenor, Daniel', 'Aldámiz-Echevarria, Teresa', 'Tejerina, Francisco', 'Diez, Cristina', 'Vázquez-Morón, Sonia', 'Resino, Salvador']",Sci Rep,,,True
e08048659491371d0387ad99e9174a4c49c83872,PMC,Structural aspects of nucleotide ligand binding by a bacterial 2H phosphoesterase,http://dx.doi.org/10.1371/journal.pone.0170355,PMC5283653,28141848,CC BY,"The 2H phosphoesterase family contains enzymes with two His-X-Ser/Thr motifs in the active site. 2H enzymes are found in all kingdoms of life, sharing little sequence identity despite the conserved overall fold and active site. For many 2H enzymes, the physiological function is unknown. Here, we studied the structure of the 2H family member LigT from Escherichia coli both in the apo form and complexed with different active-site ligands, including ATP, 2′-AMP, 3′-AMP, phosphate, and NADP(+). Comparisons to the well-characterized vertebrate myelin enzyme 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) highlight specific features of the catalytic cycle and substrate recognition in both enzymes. The role played by the helix α7, unique to CNPases within the 2H family, is apparently taken over by Arg130 in the bacterial enzyme. Other residues and loops lining the active site groove are likely to be important for RNA substrate binding. We visualized conformational changes related to ligand binding, as well as the position of the nucleophilic water molecule. We also present a low-resolution model of E. coli LigT bound to tRNA in solution, and provide a model for RNA binding by LigT, involving flexible loops lining the active site cavity. Taken together, our results both aid in understanding the common features of 2H family enzymes and help highlight the distinct features in the 2H family members, which must result in different reaction mechanisms. Unique aspects in different 2H family members can be observed in ligand recognition and binding, and in the coordination of the nucleophilic water molecule and the reactive phosphate moiety.",2017 Jan 31,"['Myllykoski, Matti', 'Kursula, Petri']",PLoS One,,,True
cb9a727c40a2c855d1ac280f2a82576f198331a7,PMC,Structural aspects of nucleotide ligand binding by a bacterial 2H phosphoesterase,http://dx.doi.org/10.1371/journal.pone.0170355,PMC5283653,28141848,CC BY,"The 2H phosphoesterase family contains enzymes with two His-X-Ser/Thr motifs in the active site. 2H enzymes are found in all kingdoms of life, sharing little sequence identity despite the conserved overall fold and active site. For many 2H enzymes, the physiological function is unknown. Here, we studied the structure of the 2H family member LigT from Escherichia coli both in the apo form and complexed with different active-site ligands, including ATP, 2′-AMP, 3′-AMP, phosphate, and NADP(+). Comparisons to the well-characterized vertebrate myelin enzyme 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) highlight specific features of the catalytic cycle and substrate recognition in both enzymes. The role played by the helix α7, unique to CNPases within the 2H family, is apparently taken over by Arg130 in the bacterial enzyme. Other residues and loops lining the active site groove are likely to be important for RNA substrate binding. We visualized conformational changes related to ligand binding, as well as the position of the nucleophilic water molecule. We also present a low-resolution model of E. coli LigT bound to tRNA in solution, and provide a model for RNA binding by LigT, involving flexible loops lining the active site cavity. Taken together, our results both aid in understanding the common features of 2H family enzymes and help highlight the distinct features in the 2H family members, which must result in different reaction mechanisms. Unique aspects in different 2H family members can be observed in ligand recognition and binding, and in the coordination of the nucleophilic water molecule and the reactive phosphate moiety.",2017 Jan 31,"['Myllykoski, Matti', 'Kursula, Petri']",PLoS One,,,False
efdc5d569bff1bbf7b2233e6b3a84a0c61a10d17,PMC,"Public pensions and unmet medical need among older people: cross-national analysis of 16 European countries, 2004–2010",http://dx.doi.org/10.1136/jech-2015-206257,PMC5284463,27965315,CC BY,"BACKGROUND: Since the onset of the Great Recession in Europe, unmet need for medical care has been increasing, especially in persons aged 65 or older. It is possible that public pensions buffer access to healthcare in older persons during times of economic crisis, but to our knowledge, this has not been tested empirically in Europe. METHODS: We integrated panel data on 16 European countries for years 2004–2010 with indicators of public pension, unemployment insurance and sickness insurance entitlement from the Comparative Welfare Entitlements Dataset and unmet need (due to cost) prevalence rates from EuroStat 2014 edition. Using country-level fixed-effects regression models, we evaluate whether greater public pension entitlement, which helps reduce old-age poverty, reduces the prevalence of unmet medical need in older persons and whether it reduces inequalities in unmet medical need across the income distribution. RESULTS: We found that each 1-unit increase in public pension entitlement is associated with a 1.11 percentage-point decline in unmet medical need due to cost among over 65s (95% CI −0.55 to −1.66). This association is strongest for the lowest income quintile (1.65 percentage points, 95% CI −1.19 to −2.10). Importantly, we found consistent evidence that out-of-pocket payments were linked with greater unmet needs, but that this association was mitigated by greater public pension entitlement (β=−1.21 percentage points, 95% CI −0.37 to −2.06). CONCLUSIONS: Greater public pension entitlement plays a crucial role in reducing inequalities in unmet medical need among older persons, especially in healthcare systems which rely heavily on out-of-pocket payments.",2017 Feb 13,"['Reeves, Aaron', 'McKee, Martin', 'Mackenbach, Johan', 'Whitehead, Margaret', 'Stuckler, David']",J Epidemiol Community Health,,,True
638877602af5c47a703bf8eb56869149082e73c4,PMC,"Public pensions and unmet medical need among older people: cross-national analysis of 16 European countries, 2004–2010",http://dx.doi.org/10.1136/jech-2015-206257,PMC5284463,27965315,CC BY,"BACKGROUND: Since the onset of the Great Recession in Europe, unmet need for medical care has been increasing, especially in persons aged 65 or older. It is possible that public pensions buffer access to healthcare in older persons during times of economic crisis, but to our knowledge, this has not been tested empirically in Europe. METHODS: We integrated panel data on 16 European countries for years 2004–2010 with indicators of public pension, unemployment insurance and sickness insurance entitlement from the Comparative Welfare Entitlements Dataset and unmet need (due to cost) prevalence rates from EuroStat 2014 edition. Using country-level fixed-effects regression models, we evaluate whether greater public pension entitlement, which helps reduce old-age poverty, reduces the prevalence of unmet medical need in older persons and whether it reduces inequalities in unmet medical need across the income distribution. RESULTS: We found that each 1-unit increase in public pension entitlement is associated with a 1.11 percentage-point decline in unmet medical need due to cost among over 65s (95% CI −0.55 to −1.66). This association is strongest for the lowest income quintile (1.65 percentage points, 95% CI −1.19 to −2.10). Importantly, we found consistent evidence that out-of-pocket payments were linked with greater unmet needs, but that this association was mitigated by greater public pension entitlement (β=−1.21 percentage points, 95% CI −0.37 to −2.06). CONCLUSIONS: Greater public pension entitlement plays a crucial role in reducing inequalities in unmet medical need among older persons, especially in healthcare systems which rely heavily on out-of-pocket payments.",2017 Feb 13,"['Reeves, Aaron', 'McKee, Martin', 'Mackenbach, Johan', 'Whitehead, Margaret', 'Stuckler, David']",J Epidemiol Community Health,,,False
307179cebf2bf9f9107f745af8f2899db6c51ca9,PMC,"Systematic, active surveillance for Middle East respiratory syndrome coronavirus in camels in Egypt",http://dx.doi.org/10.1038/emi.2016.130,PMC5285495,28050021,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe human infections and dromedary camels are considered an intermediary host. The dynamics of natural infection in camels are not well understood. Through systematic surveillance in Egypt, nasal, rectal, milk, urine and serum samples were collected from camels between June 2014 and February 2016. Locations included quarantines, markets, abattoirs, free-roaming herds and farmed breeding herds. The overall seroprevalence was 71% and RNA detection rate was 15%. Imported camels had higher seroprevalence (90% vs 61%) and higher RT-PCR detection rates (21% vs 12%) than locally raised camels. Juveniles had lower seroprevalence than adults (37% vs 82%) but similar RT-PCR detection rates (16% vs 15%). An outbreak in a breeding herd, showed that antibodies rapidly wane, that camels become re-infected, and that outbreaks in a herd are sustained for an extended time. Maternal antibodies titers were very low in calves regardless of the antibody titers of the mothers. Our results support the hypothesis that camels are a reservoir for MERS-CoV and that camel trade is an important route of introducing the virus into importing countries. Findings related to waning antibodies and re-infection have implications for camel vaccine development, disease management and zoonotic threat.",2017 Jan 4,"['Ali, Mohamed A', 'Shehata, Mahmoud M', 'Gomaa, Mokhtar R', 'Kandeil, Ahmed', 'El-Shesheny, Rabeh', 'Kayed, Ahmed S', 'El-Taweel, Ahmed N', 'Atea, Mohamed', 'Hassan, Nagla', 'Bagato, Ola', 'Moatasim, Yassmin', 'Mahmoud, Sara H', 'Kutkat, Omnia', 'Maatouq, Asmaa M', 'Osman, Ahmed', 'McKenzie, Pamela P', 'Webby, Richard J', 'Kayali, Ghazi']",Emerg Microbes Infect,,,True
948c0d351c8ed1e62fa8fc8d3c552d7f53cef048,PMC,"Systematic, active surveillance for Middle East respiratory syndrome coronavirus in camels in Egypt",http://dx.doi.org/10.1038/emi.2016.130,PMC5285495,28050021,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe human infections and dromedary camels are considered an intermediary host. The dynamics of natural infection in camels are not well understood. Through systematic surveillance in Egypt, nasal, rectal, milk, urine and serum samples were collected from camels between June 2014 and February 2016. Locations included quarantines, markets, abattoirs, free-roaming herds and farmed breeding herds. The overall seroprevalence was 71% and RNA detection rate was 15%. Imported camels had higher seroprevalence (90% vs 61%) and higher RT-PCR detection rates (21% vs 12%) than locally raised camels. Juveniles had lower seroprevalence than adults (37% vs 82%) but similar RT-PCR detection rates (16% vs 15%). An outbreak in a breeding herd, showed that antibodies rapidly wane, that camels become re-infected, and that outbreaks in a herd are sustained for an extended time. Maternal antibodies titers were very low in calves regardless of the antibody titers of the mothers. Our results support the hypothesis that camels are a reservoir for MERS-CoV and that camel trade is an important route of introducing the virus into importing countries. Findings related to waning antibodies and re-infection have implications for camel vaccine development, disease management and zoonotic threat.",2017 Jan 4,"['Ali, Mohamed A', 'Shehata, Mahmoud M', 'Gomaa, Mokhtar R', 'Kandeil, Ahmed', 'El-Shesheny, Rabeh', 'Kayed, Ahmed S', 'El-Taweel, Ahmed N', 'Atea, Mohamed', 'Hassan, Nagla', 'Bagato, Ola', 'Moatasim, Yassmin', 'Mahmoud, Sara H', 'Kutkat, Omnia', 'Maatouq, Asmaa M', 'Osman, Ahmed', 'McKenzie, Pamela P', 'Webby, Richard J', 'Kayali, Ghazi']",Emerg Microbes Infect,,,False
93b403529ab422ea1ab0606a02de845206d1c519,PMC,"Systematic, active surveillance for Middle East respiratory syndrome coronavirus in camels in Egypt",http://dx.doi.org/10.1038/emi.2016.130,PMC5285495,28050021,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe human infections and dromedary camels are considered an intermediary host. The dynamics of natural infection in camels are not well understood. Through systematic surveillance in Egypt, nasal, rectal, milk, urine and serum samples were collected from camels between June 2014 and February 2016. Locations included quarantines, markets, abattoirs, free-roaming herds and farmed breeding herds. The overall seroprevalence was 71% and RNA detection rate was 15%. Imported camels had higher seroprevalence (90% vs 61%) and higher RT-PCR detection rates (21% vs 12%) than locally raised camels. Juveniles had lower seroprevalence than adults (37% vs 82%) but similar RT-PCR detection rates (16% vs 15%). An outbreak in a breeding herd, showed that antibodies rapidly wane, that camels become re-infected, and that outbreaks in a herd are sustained for an extended time. Maternal antibodies titers were very low in calves regardless of the antibody titers of the mothers. Our results support the hypothesis that camels are a reservoir for MERS-CoV and that camel trade is an important route of introducing the virus into importing countries. Findings related to waning antibodies and re-infection have implications for camel vaccine development, disease management and zoonotic threat.",2017 Jan 4,"['Ali, Mohamed A', 'Shehata, Mahmoud M', 'Gomaa, Mokhtar R', 'Kandeil, Ahmed', 'El-Shesheny, Rabeh', 'Kayed, Ahmed S', 'El-Taweel, Ahmed N', 'Atea, Mohamed', 'Hassan, Nagla', 'Bagato, Ola', 'Moatasim, Yassmin', 'Mahmoud, Sara H', 'Kutkat, Omnia', 'Maatouq, Asmaa M', 'Osman, Ahmed', 'McKenzie, Pamela P', 'Webby, Richard J', 'Kayali, Ghazi']",Emerg Microbes Infect,,,False
65bf3c106e3599bc88c91813478e02d8006b54eb,PMC,"Systematic, active surveillance for Middle East respiratory syndrome coronavirus in camels in Egypt",http://dx.doi.org/10.1038/emi.2016.130,PMC5285495,28050021,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe human infections and dromedary camels are considered an intermediary host. The dynamics of natural infection in camels are not well understood. Through systematic surveillance in Egypt, nasal, rectal, milk, urine and serum samples were collected from camels between June 2014 and February 2016. Locations included quarantines, markets, abattoirs, free-roaming herds and farmed breeding herds. The overall seroprevalence was 71% and RNA detection rate was 15%. Imported camels had higher seroprevalence (90% vs 61%) and higher RT-PCR detection rates (21% vs 12%) than locally raised camels. Juveniles had lower seroprevalence than adults (37% vs 82%) but similar RT-PCR detection rates (16% vs 15%). An outbreak in a breeding herd, showed that antibodies rapidly wane, that camels become re-infected, and that outbreaks in a herd are sustained for an extended time. Maternal antibodies titers were very low in calves regardless of the antibody titers of the mothers. Our results support the hypothesis that camels are a reservoir for MERS-CoV and that camel trade is an important route of introducing the virus into importing countries. Findings related to waning antibodies and re-infection have implications for camel vaccine development, disease management and zoonotic threat.",2017 Jan 4,"['Ali, Mohamed A', 'Shehata, Mahmoud M', 'Gomaa, Mokhtar R', 'Kandeil, Ahmed', 'El-Shesheny, Rabeh', 'Kayed, Ahmed S', 'El-Taweel, Ahmed N', 'Atea, Mohamed', 'Hassan, Nagla', 'Bagato, Ola', 'Moatasim, Yassmin', 'Mahmoud, Sara H', 'Kutkat, Omnia', 'Maatouq, Asmaa M', 'Osman, Ahmed', 'McKenzie, Pamela P', 'Webby, Richard J', 'Kayali, Ghazi']",Emerg Microbes Infect,,,False
6a9ea9f5ca4cad07c10b3a792321cebfd189e5f7,PMC,"Systematic, active surveillance for Middle East respiratory syndrome coronavirus in camels in Egypt",http://dx.doi.org/10.1038/emi.2016.130,PMC5285495,28050021,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe human infections and dromedary camels are considered an intermediary host. The dynamics of natural infection in camels are not well understood. Through systematic surveillance in Egypt, nasal, rectal, milk, urine and serum samples were collected from camels between June 2014 and February 2016. Locations included quarantines, markets, abattoirs, free-roaming herds and farmed breeding herds. The overall seroprevalence was 71% and RNA detection rate was 15%. Imported camels had higher seroprevalence (90% vs 61%) and higher RT-PCR detection rates (21% vs 12%) than locally raised camels. Juveniles had lower seroprevalence than adults (37% vs 82%) but similar RT-PCR detection rates (16% vs 15%). An outbreak in a breeding herd, showed that antibodies rapidly wane, that camels become re-infected, and that outbreaks in a herd are sustained for an extended time. Maternal antibodies titers were very low in calves regardless of the antibody titers of the mothers. Our results support the hypothesis that camels are a reservoir for MERS-CoV and that camel trade is an important route of introducing the virus into importing countries. Findings related to waning antibodies and re-infection have implications for camel vaccine development, disease management and zoonotic threat.",2017 Jan 4,"['Ali, Mohamed A', 'Shehata, Mahmoud M', 'Gomaa, Mokhtar R', 'Kandeil, Ahmed', 'El-Shesheny, Rabeh', 'Kayed, Ahmed S', 'El-Taweel, Ahmed N', 'Atea, Mohamed', 'Hassan, Nagla', 'Bagato, Ola', 'Moatasim, Yassmin', 'Mahmoud, Sara H', 'Kutkat, Omnia', 'Maatouq, Asmaa M', 'Osman, Ahmed', 'McKenzie, Pamela P', 'Webby, Richard J', 'Kayali, Ghazi']",Emerg Microbes Infect,,,False
741d9ac96e2951be86d4f57d5dac2121953fe3bc,PMC,"Identification and evolutionary dynamics of two novel human coronavirus OC43 genotypes associated with acute respiratory infections: phylogenetic, spatiotemporal and transmission network analyses",http://dx.doi.org/10.1038/emi.2016.132,PMC5285497,28050020,CC BY,"Human coronavirus OC43 (HCoV-OC43) is commonly associated with respiratory tract infections in humans, with five genetically distinct genotypes (A to E) described so far. In this study, we obtained the full-length genomes of HCoV-OC43 strains from two previously unrecognized lineages identified among patients presenting with severe upper respiratory tract symptoms in a cross-sectional molecular surveillance study in Kuala Lumpur, Malaysia, between 2012 and 2013. Phylogenetic, recombination and comparative genomic analyses revealed two distinct clusters diverging from a genotype D-like common ancestor through recombination with a putative genotype A-like lineage in the non-structural protein (nsp) 10 gene. Signature amino acid substitutions and a glycine residue insertion at the N-terminal domain of the S1 subunit of the spike gene, among others, exhibited further distinction in a recombination pattern, to which these clusters were classified as genotypes F and G. The phylogeographic mapping of the global spike gene indicated that the genetically similar HCoV-OC43 genotypes F and G strains were potentially circulating in China, Japan, Thailand and Europe as early as the late 2000s. The transmission network construction based on the TN93 pairwise genetic distance revealed the emergence and persistence of multiple sub-epidemic clusters of the highly prevalent genotype D and its descendant genotypes F and G, which contributed to the spread of HCoV-OC43 in the region. Finally, a more consistent nomenclature system for non-recombinant and recombinant HCoV-OC43 lineages is proposed, taking into account genetic recombination as an important feature in HCoV evolution and classification.",2017 Jan 4,"['Oong, Xiang Yong', 'Ng, Kim Tien', 'Takebe, Yutaka', 'Ng, Liang Jie', 'Chan, Kok Gan', 'Chook, Jack Bee', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Emerg Microbes Infect,,,True
a5fe0a887b0006387c3897745e4622442ac039c3,PMC,"Identification and evolutionary dynamics of two novel human coronavirus OC43 genotypes associated with acute respiratory infections: phylogenetic, spatiotemporal and transmission network analyses",http://dx.doi.org/10.1038/emi.2016.132,PMC5285497,28050020,CC BY,"Human coronavirus OC43 (HCoV-OC43) is commonly associated with respiratory tract infections in humans, with five genetically distinct genotypes (A to E) described so far. In this study, we obtained the full-length genomes of HCoV-OC43 strains from two previously unrecognized lineages identified among patients presenting with severe upper respiratory tract symptoms in a cross-sectional molecular surveillance study in Kuala Lumpur, Malaysia, between 2012 and 2013. Phylogenetic, recombination and comparative genomic analyses revealed two distinct clusters diverging from a genotype D-like common ancestor through recombination with a putative genotype A-like lineage in the non-structural protein (nsp) 10 gene. Signature amino acid substitutions and a glycine residue insertion at the N-terminal domain of the S1 subunit of the spike gene, among others, exhibited further distinction in a recombination pattern, to which these clusters were classified as genotypes F and G. The phylogeographic mapping of the global spike gene indicated that the genetically similar HCoV-OC43 genotypes F and G strains were potentially circulating in China, Japan, Thailand and Europe as early as the late 2000s. The transmission network construction based on the TN93 pairwise genetic distance revealed the emergence and persistence of multiple sub-epidemic clusters of the highly prevalent genotype D and its descendant genotypes F and G, which contributed to the spread of HCoV-OC43 in the region. Finally, a more consistent nomenclature system for non-recombinant and recombinant HCoV-OC43 lineages is proposed, taking into account genetic recombination as an important feature in HCoV evolution and classification.",2017 Jan 4,"['Oong, Xiang Yong', 'Ng, Kim Tien', 'Takebe, Yutaka', 'Ng, Liang Jie', 'Chan, Kok Gan', 'Chook, Jack Bee', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Emerg Microbes Infect,,,False
94d2ebfc7a2a0ffc00b05ce8031fdfef3255af4a,PMC,The first imported case of Rift Valley fever in China reveals a genetic reassortment of different viral lineages,http://dx.doi.org/10.1038/emi.2016.136,PMC5285499,28096531,CC BY,"We report the first imported case of Rift Valley fever (RVF) in China. The patient returned from Angola, a non-epidemic country, with an infection of a new reassortant from different lineages of Rift Valley fever viruses (RVFVs). The patient developed multiorgan dysfunction and gradually recovered with continuous renal replacement therapy and a short regimen of methylprednisolone treatment. The disordered cytokines and chemokines in the plasma of the patient revealed hypercytokinemia, but the levels of protective cytokines were low upon admission and fluctuated as the disease improved. Whole-genome sequencing and phylogenetic analysis revealed that the imported strain was a reassortant comprising the L and M genes from lineage E and the S gene from lineage A. This case highlights that RVFV had undergone genetic reassortment, which could potentially alter its biological properties, cause large outbreaks and pose a serious threat to global public health as well as the livestock breeding industry.",2017 Jan 18,"['Liu, Jingyuan', 'Sun, Yulan', 'Shi, Weifeng', 'Tan, Shuguang', 'Pan, Yang', 'Cui, Shujuan', 'Zhang, Qingchao', 'Dou, Xiangfeng', 'Lv, Yanning', 'Li, Xinyu', 'Li, Xitai', 'Chen, Lijuan', 'Quan, Chuansong', 'Wang, Qianli', 'Zhao, Yingze', 'lv, Qiang', 'Hua, Wenhao', 'Zeng, Hui', 'Chen, Zhihai', 'Xiong, Haofeng', 'Jiang, Chengyu', 'Pang, Xinghuo', 'Zhang, Fujie', 'Liang, Mifang', 'Wu, Guizhen', 'Gao, George F', 'Liu, William J', 'Li, Ang', 'Wang, Quanyi']",Emerg Microbes Infect,,,True
192216ea71dcb7a9edb56ef32c0460d97eeab9d2,PMC,The first imported case of Rift Valley fever in China reveals a genetic reassortment of different viral lineages,http://dx.doi.org/10.1038/emi.2016.136,PMC5285499,28096531,CC BY,"We report the first imported case of Rift Valley fever (RVF) in China. The patient returned from Angola, a non-epidemic country, with an infection of a new reassortant from different lineages of Rift Valley fever viruses (RVFVs). The patient developed multiorgan dysfunction and gradually recovered with continuous renal replacement therapy and a short regimen of methylprednisolone treatment. The disordered cytokines and chemokines in the plasma of the patient revealed hypercytokinemia, but the levels of protective cytokines were low upon admission and fluctuated as the disease improved. Whole-genome sequencing and phylogenetic analysis revealed that the imported strain was a reassortant comprising the L and M genes from lineage E and the S gene from lineage A. This case highlights that RVFV had undergone genetic reassortment, which could potentially alter its biological properties, cause large outbreaks and pose a serious threat to global public health as well as the livestock breeding industry.",2017 Jan 18,"['Liu, Jingyuan', 'Sun, Yulan', 'Shi, Weifeng', 'Tan, Shuguang', 'Pan, Yang', 'Cui, Shujuan', 'Zhang, Qingchao', 'Dou, Xiangfeng', 'Lv, Yanning', 'Li, Xinyu', 'Li, Xitai', 'Chen, Lijuan', 'Quan, Chuansong', 'Wang, Qianli', 'Zhao, Yingze', 'lv, Qiang', 'Hua, Wenhao', 'Zeng, Hui', 'Chen, Zhihai', 'Xiong, Haofeng', 'Jiang, Chengyu', 'Pang, Xinghuo', 'Zhang, Fujie', 'Liang, Mifang', 'Wu, Guizhen', 'Gao, George F', 'Liu, William J', 'Li, Ang', 'Wang, Quanyi']",Emerg Microbes Infect,,,False
634b8c282afdd06201cb2531fb70985d92270271,PMC,In Situ Tagged nsp15 Reveals Interactions with Coronavirus Replication/Transcription Complex-Associated Proteins,http://dx.doi.org/10.1128/mBio.02320-16,PMC5285509,28143984,CC BY,"Coronavirus (CoV) replication and transcription are carried out in close proximity to restructured endoplasmic reticulum (ER) membranes in replication/transcription complexes (RTC). Many of the CoV nonstructural proteins (nsps) are required for RTC function; however, not all of their functions are known. nsp15 contains an endoribonuclease domain that is conserved in the CoV family. While the enzymatic activity and crystal structure of nsp15 are well defined, its role in replication remains elusive. nsp15 localizes to sites of RNA replication, but whether it acts independently or requires additional interactions for its function remains unknown. To begin to address these questions, we created an in situ tagged form of nsp15 using the prototypic CoV, mouse hepatitis virus (MHV). In MHV, nsp15 contains the genomic RNA packaging signal (P/S), a 95-bp RNA stem-loop structure that is not required for viral replication or nsp15 function. Utilizing this knowledge, we constructed an internal hemagglutinin (HA) tag that replaced the P/S. We found that nsp15-HA was localized to discrete perinuclear puncta and strongly colocalized with nsp8 and nsp12, both well-defined members of the RTC, but not the membrane (M) protein, involved in virus assembly. Finally, we found that nsp15 interacted with RTC-associated proteins nsp8 and nsp12 during infection, and this interaction was RNA independent. From this, we conclude that nsp15 localizes and interacts with CoV proteins in the RTC, suggesting it plays a direct or indirect role in virus replication. Furthermore, the use of in situ epitope tags could be used to determine novel nsp-nsp interactions in coronaviruses.",2017 Jan 31,"['Athmer, Jeremiah', 'Fehr, Anthony R.', 'Grunewald, Matthew', 'Smith, Everett Clinton', 'Denison, Mark R.', 'Perlman, Stanley']",mBio,,,True
713f2cff38e6555558825cb304f67eb31c35687f,PMC,Doxycycline Induces Mitophagy and Suppresses Production of Interferon-β in IPEC-J2 Cells,http://dx.doi.org/10.3389/fcimb.2017.00021,PMC5285722,28203548,CC BY,"Previous reports have demonstrated that the second-generation tetracycline derivative doxycycline (DOX) interrupts mitochondrial proteostasis and physiology, inhibits proliferation of many cell types, and induces apoptosis. However, the effects of DOX, which is widely used in porcine husbandry by feed, on the porcine intestinal epithelium are unclear. In this study, we demonstrated that DOX damaged mitochondrial morphology and induced the co-localization of mitochondria with autophagosomes, suggesting that DOX induces mitophagy in IPEC-J2 cells. We also found evidence that DOX increased intracellular levels of reactive oxygen species (ROS) or mitochondrial-specific ROS in a dose dependent manner. Moreover, 50 μg/ml DOX significantly decreased production of interferon-β and facilitated replication of transmissible gastroenteritis coronavirus in IPEC-J2 cells. These results demonstrated that DOX induced mitophagy and ROS production, which damaged the intestinal epithelium. As DOX is used extensively in pig husbandry, uncontrolled application poses a significant threat of viral infection, so stricter policies on its usage should be required.",2017 Feb 1,"['Xing, Yang', 'Liqi, Zhu', 'Jian, Lin', 'Qinghua, Yu', 'Qian, Yang']",Front Cell Infect Microbiol,,,True
eb657ff6a2abb31f6e8c6c9ac91814cb8fcda133,PMC,Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis) with atypical encephalitis and painful testitis: a case report,http://dx.doi.org/10.1186/s12883-017-0807-4,PMC5286801,28143446,CC BY,"BACKGROUND: Kikuchi-Fujimoto disease is a self-limited clinicopathologic entity that is increasingly recognized worldwide. Kikuchi-Fujimoto disease is characterized by cervical lymphadenopathy occurring in young adults. Neurologic involvement is rare, and testitis directly caused by Kikuchi-Fujimoto disease has not yet been reported. CASE PRESENTATION: A 19-year-old man was brought to our clinic with complaints of fever, headache, fatigue, and left lower quadrant pain that had persisted for 3 weeks. On physical examination, painful cervical lymphadenopathies were observed. Meningitis was suspected based on a cerebrospinal fluid examination, and left-sided orchitis was diagnosed based on findings from magnetic resonance imaging and ultrasonography. However, neither antibiotics nor antiviral drugs were effective in treating the patient’s symptoms. On the 20(th) day of hospitalization, the patient experienced a loss of consciousness, and brain T2-weighted magnetic resonance imaging showed asymmetrical, high-signal intensities in both basal nuclei and the left temporal lobe. Encephalitis was suspected, and the patient was treated with intravenous prednisolone pulse therapy (1 g/day) for 3 days and intravenous immunoglobulin therapy for 5 days. A left cervical lymph node biopsy showed apoptotic necrosis in paracortical and cortical areas with an abundance of macrophages and large lymphoid cells, which had irregular nuclei suggestive of Kikuchi-Fujimoto disease; the pathological findings from a brain biopsy were the same as those of the cervical lymph node biopsy. The encephalitis and cervical lymphadenopathies followed a benign course, as did the testitis. CONCLUSIONS: This is the first report of Kikuchi-Fujimoto disease involving painful testitis and pathologically proven asymmetrical brain regions. Kikuchi-Fujimoto disease should be included in the differential diagnosis when a patient presents with encephalitis, testitis, and fever of unknown origin.",2017 Feb 1,"['Kido, Hidenori', 'Kano, Osamu', 'Hamai, Asami', 'Masuda, Hiroyuki', 'Fuchinoue, Yutaka', 'Nemoto, Masaaki', 'Arai, Chiaki', 'Takeda, Teppei', 'Yamabe, Fumihito', 'Tai, Toshihiro', 'Kasahara, Mizuki', 'Suzuki, Kenichi', 'Shiraga, Nobuyuki', 'Sadamoto, Sota', 'Wakayama, Megumi', 'Takahashi, Yukitoshi', 'Iwasaki, Yasuo', 'Shibuya, Kazutoshi', 'Urita, Yoshihisa']",BMC Neurol,,,True
ad8462ee6be4cf7ab5b17b2b81c713879c599a73,PMC,The conserved macrodomains of the non-structural proteins of Chikungunya virus and other pathogenic positive strand RNA viruses function as mono-ADP-ribosylhydrolases,http://dx.doi.org/10.1038/srep41746,PMC5288732,28150709,CC BY,"Human pathogenic positive single strand RNA ((+)ssRNA) viruses, including Chikungunya virus, pose severe health problems as for many neither efficient vaccines nor therapeutic strategies exist. To interfere with propagation, viral enzymatic activities are considered potential targets. Here we addressed the function of the viral macrodomains, conserved folds of non-structural proteins of many (+)ssRNA viruses. Macrodomains are closely associated with ADP-ribose function and metabolism. ADP-ribosylation is a post-translational modification controlling various cellular processes, including DNA repair, transcription and stress response. We found that the viral macrodomains possess broad hydrolase activity towards mono-ADP-ribosylated substrates of the mono-ADP-ribosyltransferases ARTD7, ARTD8 and ARTD10 (aka PARP15, PARP14 and PARP10, respectively), reverting this post-translational modification both in vitro and in cells. In contrast, the viral macrodomains possess only weak activity towards poly-ADP-ribose chains synthesized by ARTD1 (aka PARP1). Unlike poly-ADP-ribosylglycohydrolase, which hydrolyzes poly-ADP-ribose chains to individual ADP-ribose units but cannot cleave the amino acid side chain - ADP-ribose bond, the different viral macrodomains release poly-ADP-ribose chains with distinct efficiency. Mutational and structural analyses identified key amino acids for hydrolase activity of the Chikungunya viral macrodomain. Moreover, ARTD8 and ARTD10 are induced by innate immune mechanisms, suggesting that the control of mono-ADP-ribosylation is part of a host-pathogen conflict.",2017 Feb 2,"['Eckei, Laura', 'Krieg, Sarah', 'Bütepage, Mareike', 'Lehmann, Anne', 'Gross, Annika', 'Lippok, Barbara', 'Grimm, Alexander R.', 'Kümmerer, Beate M.', 'Rossetti, Giulia', 'Lüscher, Bernhard', 'Verheugd, Patricia']",Sci Rep,,,True
4adfe283d67f5acdffa1c048de3fd5ff70495083,PMC,The conserved macrodomains of the non-structural proteins of Chikungunya virus and other pathogenic positive strand RNA viruses function as mono-ADP-ribosylhydrolases,http://dx.doi.org/10.1038/srep41746,PMC5288732,28150709,CC BY,"Human pathogenic positive single strand RNA ((+)ssRNA) viruses, including Chikungunya virus, pose severe health problems as for many neither efficient vaccines nor therapeutic strategies exist. To interfere with propagation, viral enzymatic activities are considered potential targets. Here we addressed the function of the viral macrodomains, conserved folds of non-structural proteins of many (+)ssRNA viruses. Macrodomains are closely associated with ADP-ribose function and metabolism. ADP-ribosylation is a post-translational modification controlling various cellular processes, including DNA repair, transcription and stress response. We found that the viral macrodomains possess broad hydrolase activity towards mono-ADP-ribosylated substrates of the mono-ADP-ribosyltransferases ARTD7, ARTD8 and ARTD10 (aka PARP15, PARP14 and PARP10, respectively), reverting this post-translational modification both in vitro and in cells. In contrast, the viral macrodomains possess only weak activity towards poly-ADP-ribose chains synthesized by ARTD1 (aka PARP1). Unlike poly-ADP-ribosylglycohydrolase, which hydrolyzes poly-ADP-ribose chains to individual ADP-ribose units but cannot cleave the amino acid side chain - ADP-ribose bond, the different viral macrodomains release poly-ADP-ribose chains with distinct efficiency. Mutational and structural analyses identified key amino acids for hydrolase activity of the Chikungunya viral macrodomain. Moreover, ARTD8 and ARTD10 are induced by innate immune mechanisms, suggesting that the control of mono-ADP-ribosylation is part of a host-pathogen conflict.",2017 Feb 2,"['Eckei, Laura', 'Krieg, Sarah', 'Bütepage, Mareike', 'Lehmann, Anne', 'Gross, Annika', 'Lippok, Barbara', 'Grimm, Alexander R.', 'Kümmerer, Beate M.', 'Rossetti, Giulia', 'Lüscher, Bernhard', 'Verheugd, Patricia']",Sci Rep,,,False
2896c5193ae79e31e46c2eb50590dc8d58fe9a44,PMC,In Vivo Persistence of Human Rhinoviruses in Immunosuppressed Patients,http://dx.doi.org/10.1371/journal.pone.0170774,PMC5289482,28151988,CC BY,"Several species of the genus Enterovirus cause persistent infections in humans. Human rhinovirus (HRV) infections are generally self-limiting but occasionally persistent infections have been described. This study aimed to identify persistent HRV infections and investigate the clinical and virologic characteristics of patients with persistent infections. From January 2012 to March 2015, 3714 respiratory specimens from 2608 patients were tested for respiratory viruses by using a multiplex reverse transcription–polymerase chain reaction. A retrospective study was performed. Patients with at least two specimens positive for HRV/enterovirus taken 45 days or longer apart were identified and the HRV/enteroviruses were typed. Patients with persistent infection were compared to patients with reinfection and patients with cleared infection. Phylogenetic analysis of the viral protein(VP)4/VP2 region was performed. 18 patients with persistent HRV/enterovirus infection were identified. Minimum median duration of persistence was 92 days (range 50–455 days). All but one patients with persistence were immunosuppressed. Immunosuppression and hematologic disorders were more frequent in patients with persistence (n = 18) than in patients with reinfection (n = 33) and with cleared infection (n = 25) (p = 0.003 and p = 0.001, respectively). In conclusion, this retrospective study identified HRV persistence in vivo which occurred mainly in immunosuppressed patients.",2017 Feb 2,"['Engelmann, Ilka', 'Dewilde, Anny', 'Lazrek, Mouna', 'Batteux, Mathilde', 'Hamissi, Aminati', 'Yakoub-Agha, Ibrahim', 'Hober, Didier']",PLoS One,,,True
81f6d476d70cdce38efdd5e0448e565d78f4b85c,PMC,Signatures of malaria-associated pathology revealed by high-resolution whole-blood transcriptomics in a rodent model of malaria,http://dx.doi.org/10.1038/srep41722,PMC5290525,28155887,CC BY,"The influence of parasite genetic factors on immune responses and development of severe pathology of malaria is largely unknown. In this study, we performed genome-wide transcriptomic profiling of mouse whole blood during blood-stage infections of two strains of the rodent malaria parasite Plasmodium chabaudi that differ in virulence. We identified several transcriptomic signatures associated with the virulent infection, including signatures for platelet aggregation, stronger and prolonged anemia and lung inflammation. The first two signatures were detected prior to pathology. The anemia signature indicated deregulation of host erythropoiesis, and the lung inflammation signature was linked to increased neutrophil infiltration, more cell death and greater parasite sequestration in the lungs. This comparative whole-blood transcriptomics profiling of virulent and avirulent malaria shows the validity of this approach to inform severity of the infection and provide insight into pathogenic mechanisms.",2017 Feb 3,"['Lin, Jing-wen', 'Sodenkamp, Jan', 'Cunningham, Deirdre', 'Deroost, Katrien', 'Tshitenge, Tshibuayi Christine', 'McLaughlin, Sarah', 'Lamb, Tracey J.', 'Spencer-Dene, Bradley', 'Hosking, Caroline', 'Ramesar, Jai', 'Janse, Chris J.', 'Graham, Christine', 'O’Garra, Anne', 'Langhorne, Jean']",Sci Rep,,,True
8ceb804dbd3140461f00314ad42384f5c02c5e78,PMC,Signatures of malaria-associated pathology revealed by high-resolution whole-blood transcriptomics in a rodent model of malaria,http://dx.doi.org/10.1038/srep41722,PMC5290525,28155887,CC BY,"The influence of parasite genetic factors on immune responses and development of severe pathology of malaria is largely unknown. In this study, we performed genome-wide transcriptomic profiling of mouse whole blood during blood-stage infections of two strains of the rodent malaria parasite Plasmodium chabaudi that differ in virulence. We identified several transcriptomic signatures associated with the virulent infection, including signatures for platelet aggregation, stronger and prolonged anemia and lung inflammation. The first two signatures were detected prior to pathology. The anemia signature indicated deregulation of host erythropoiesis, and the lung inflammation signature was linked to increased neutrophil infiltration, more cell death and greater parasite sequestration in the lungs. This comparative whole-blood transcriptomics profiling of virulent and avirulent malaria shows the validity of this approach to inform severity of the infection and provide insight into pathogenic mechanisms.",2017 Feb 3,"['Lin, Jing-wen', 'Sodenkamp, Jan', 'Cunningham, Deirdre', 'Deroost, Katrien', 'Tshitenge, Tshibuayi Christine', 'McLaughlin, Sarah', 'Lamb, Tracey J.', 'Spencer-Dene, Bradley', 'Hosking, Caroline', 'Ramesar, Jai', 'Janse, Chris J.', 'Graham, Christine', 'O’Garra, Anne', 'Langhorne, Jean']",Sci Rep,,,False
3d8ad2b7cceac3f97d193df3beb627b05860c499,PMC,Assessment of the efficacy of two novel DNA vaccine formulations against highly pathogenic Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1038/srep41886,PMC5291100,28157199,CC BY,"Since May 2006, a highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has emerged and prevailed in mainland China, affecting over 2 million pigs. Commercial PRRSV killed and modified live vaccines cannot provide complete protection against HP-PRRSV due to genetic variation. Development of more effective vaccines against the emerging HP-PRRSV is urgently required. In our previous studies, two formulations of DNA vaccines (pcDNA3.1-PoIFN-λ1-SynORF5 and BPEI/PLGA-SynORF5) based on the HP-PRRSV were constructed and shown to induce enhanced humoral and cellular immune responses in mice. The objective of this study was to evaluate the immune response induced by these novel formulations in piglets. PcDNA3.1-PoIFN-λ1-SynORF5 and BPEI/PLGA-SynORF5 vaccines induced significantly enhanced GP5-specific antibody and PRRSV-specific neutralizing antibody in pigs compared with the pcDNA3.1-SynORF5 parental construct. Though IFN-γ levels and lymphocyte proliferation responses induced by the two DNA vaccine formulations were comparable to that induced by the pcDNA3.1-SynORF5 construct, each of the novel formulations provided efficient protection against challenge with HP-PRRSV. Non-severe clinical signs and rectal temperatures were observed in pigs immunized with BPEI/PLGA-SynORF5 compared with other groups. Thus, these novel DNA constructs may represent promising candidate vaccines against emerging HP-PRRSV.",2017 Feb 3,"['Du, Luping', 'Pang, Fengjiao', 'Yu, Zhengyu', 'Xu, Xiangwei', 'Fan, Baochao', 'Huang, Kehe', 'He, Kongwang', 'Li, Bin']",Sci Rep,,,True
a8119ed9e9815a775ecff9c603542fe9ff7ae725,PMC,Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome,http://dx.doi.org/10.1093/nar/gkw432,PMC5291261,27298260,CC BY,"The long terminal repeat (LTR) of the proviral human immunodeficiency virus (HIV)-1 genome is integral to virus transcription and host cell infection. The guanine-rich U3 region within the LTR promoter, previously shown to form G-quadruplex structures, represents an attractive target to inhibit HIV transcription and replication. In this work, we report the structure of a biologically relevant G-quadruplex within the LTR promoter region of HIV-1. The guanine-rich sequence designated LTR-IV forms a well-defined structure in physiological cationic solution. The nuclear magnetic resonance (NMR) structure of this sequence reveals a parallel-stranded G-quadruplex containing a single-nucleotide thymine bulge, which participates in a conserved stacking interaction with a neighboring single-nucleotide adenine loop. Transcription analysis in a HIV-1 replication competent cell indicates that the LTR-IV region may act as a modulator of G-quadruplex formation in the LTR promoter. Consequently, the LTR-IV G-quadruplex structure presented within this work could represent a valuable target for the design of HIV therapeutics.",2016 Jul 27,"['De\xa0Nicola, Beatrice', 'Lech, Christopher J.', 'Heddi, Brahim', 'Regmi, Sagar', 'Frasson, Ilaria', 'Perrone, Rosalba', 'Richter, Sara N.', 'Phan, Anh Tuân']",Nucleic Acids Res,,,True
3f1c348d20cfb3f5322bd3b22099a79c660456e1,PMC,Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome,http://dx.doi.org/10.1093/nar/gkw432,PMC5291261,27298260,CC BY,"The long terminal repeat (LTR) of the proviral human immunodeficiency virus (HIV)-1 genome is integral to virus transcription and host cell infection. The guanine-rich U3 region within the LTR promoter, previously shown to form G-quadruplex structures, represents an attractive target to inhibit HIV transcription and replication. In this work, we report the structure of a biologically relevant G-quadruplex within the LTR promoter region of HIV-1. The guanine-rich sequence designated LTR-IV forms a well-defined structure in physiological cationic solution. The nuclear magnetic resonance (NMR) structure of this sequence reveals a parallel-stranded G-quadruplex containing a single-nucleotide thymine bulge, which participates in a conserved stacking interaction with a neighboring single-nucleotide adenine loop. Transcription analysis in a HIV-1 replication competent cell indicates that the LTR-IV region may act as a modulator of G-quadruplex formation in the LTR promoter. Consequently, the LTR-IV G-quadruplex structure presented within this work could represent a valuable target for the design of HIV therapeutics.",2016 Jul 27,"['De\xa0Nicola, Beatrice', 'Lech, Christopher J.', 'Heddi, Brahim', 'Regmi, Sagar', 'Frasson, Ilaria', 'Perrone, Rosalba', 'Richter, Sara N.', 'Phan, Anh Tuân']",Nucleic Acids Res,,,False
cb2072b85cfa7e151150b5ecea189ea22134f4d7,PMC,"The potential influence of human parainfluenza viruses detected during hospitalization among critically ill patients in Kuwait, 2013–2015",http://dx.doi.org/10.1186/s12985-017-0681-0,PMC5291994,28159006,CC BY,"BACKGROUND: The four types of human parainfluenza viruses (PIV) are important causes of community-acquired pneumonia, particularly in children; however, limited information exists about the incidence of PIV in critically ill patients. The aim of this study is to describe the spectrum, incidence and clinical features of PIV-associated infections diagnosed during the hospital stay of patients admitted to pediatric intensive care unit (PICU) and intensive care unit (ICU) of 5 medical centers across Kuwait. METHODS: This was a population-based, retrospective study from 2013 to 2015. Specimens were analyzed by molecular methods. This analysis was performed using the database of Virology Unit, Mubarak Al-Kabeer Hospital. Data from 1510 admitted patients with suspected respiratory viral infections was extracted. RESULTS: The database contained a total of 39 (2.6%) patients infected with PIV (53.8% male and 46.2% females) and 20 (51.3%) were under 1 year of age. The most frequently isolated type was type 3 (28, 71.8%) followed by type 1 (9, 23.1%). At admission the most common clinical diagnosis was pneumonia in 12 patients (30.8%, p < 0.05) followed by bronchiolitis in 10 patients (25.6%). CONCLUSION: PIV plays an important yet unrecognized role in the outcomes of PIUC and ICU patients. Our results contribute to the limited epidemiologic data of PIV in PIUC and ICU in this region.",2017 Feb 3,"['Essa, Sahar', 'Al-tawalah, Haya', 'AlShamali, Sarah', 'Al-Nakib, Widad']",Virol J,,,True
b1d62ed79fe0391283061a488e3d43be2c03807a,PMC,Multiple Viral Infection Detected from Influenza-Like Illness Cases in Indonesia,http://dx.doi.org/10.1155/2017/9541619,PMC5292373,28232948,CC BY,"Influenza is one of the common etiologies of the upper respiratory tract infection (URTI). However, influenza virus only contributes about 20 percent of influenza-like illness patients. The aim of the study is to investigate the other viral etiologies from ILI cases in Indonesia. Of the 334 samples, 266 samples (78%) were positive at least for one virus, including 107 (42%) cases of multiple infections. Influenza virus is the most detected virus. The most frequent combination of viruses identified was adenovirus and human rhinovirus. This recent study demonstrated high detection rate of several respiratory viruses from ILI cases in Indonesia. Further studies to determine the relationship between viruses and clinical features are needed to improve respiratory disease control program.",2017 Jan 23,"['Adam, Kindi', 'Pangesti, Krisna Nur Andriana', 'Setiawaty, Vivi']",Biomed Res Int,,,True
6a246d3621609eba5e7fb36c483280aa9cacd166,PMC,Vesicular Stomatitis Virus-Vectored Multi-Antigen Tuberculosis Vaccine Limits Bacterial Proliferation in Mice following a Single Intranasal Dose,http://dx.doi.org/10.3389/fcimb.2017.00034,PMC5293745,28224119,CC BY,"Tuberculosis (TB) remains a serious health problem worldwide, and an urgent need exists to improve or replace the available vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG). Most vaccination protocols adapt two or three doses to induce long-term lasting immunity. Our previous study showed that the naked DNA encoding the triple-antigen fusion TFP846 (Rv3615c-Mtb10.4-Rv2660c) induced robust T cellular immune responses accompanying four inoculations against mycobacteria infection. However, a number of compliance issues exist in some areas lacking the appropriate medical infrastructure with multiple administrations. In this study, a novel vesicular stomatitis virus expressing TFP846 (VSV-846) was developed and the immune responses elicited by VSV-846 were evaluated. We observed that intranasal delivery of VSV-846 induced a potent antigen-specific T cell response following a single dose and VSV-846 efficiently controlled bacterial growth to levels ~10-fold lower than that observed in the mock group 6 weeks post-infection in BCG-infected mice. Importantly, mice immunized with VSV-846 provided long-term protection against mycobacteria infection compared with those receiving p846 or BCG immunization. Increased memory T cells were also observed in the spleens of VSV-846-vaccinated mice, which could be a potential mechanism associated with long-term protective immune response. These findings supported the use of VSV as an antigen delivery vector with the potential for TB vaccine development.",2017 Feb 7,"['Zhang, Ming', 'Dong, Chunsheng', 'Xiong, Sidong']",Front Cell Infect Microbiol,,,True
ebbad96c3af4aba4be4a1be0d79d535aff8a1551,PMC,Acute Hemorrhagic Edema of Infancy after Coronavirus Infection with Recurrent Rash,http://dx.doi.org/10.1155/2017/5637503,PMC5294357,28243478,CC BY,"Purpura, particularly when accompanied by fever, is a worrisome finding in children. Acute hemorrhagic edema of infancy (AHEI) is a benign type of small-vessel leukocytoclastic vasculitis that presents with progressive purpura and has an excellent prognosis. Patients with AHEI present with large, target-like purpuric plaques affecting the face, ear lobes, and extremities. While the rapid onset of these skin findings can be dramatic, the child with AHEI is usually well appearing with reassuring laboratory testing. We describe a case of a previously healthy 8-month-old female who presented with progressive purpura in a nondependent distribution, low-grade fevers, and extremity swelling. An extensive workup was performed prior to making the diagnosis of AHEI. Coronavirus was implicated as the likely triggering pathogen, and the patient suffered a recurrence of purpuric rash and swelling several weeks after her initial presentation.",2017 Jan 24,"['Chesser, Hannah', 'Chambliss, Jeffrey M.', 'Zwemer, Eric']",Case Rep Pediatr,,,True
3bda17d21aee670c29e22635d622b780820572af,PMC,A touchdown nucleic acid amplification protocol as an alternative to culture backup for immunofluorescence in the routine diagnosis of acute viral respiratory tract infections,http://dx.doi.org/10.1186/1471-2180-4-41,PMC529439,15504232,CC BY,"BACKGROUND: Immunofluorescence and virus culture are the main methods used to diagnose acute respiratory virus infections. Diagnosing these infections using nucleic acid amplification presents technical challenges, one of which is facilitating the different optimal annealing temperatures needed for each virus. To overcome this problem we developed a diagnostic molecular strip which combined a generic nested touchdown protocol with in-house primer master-mixes that could recognise 12 common respiratory viruses. RESULTS: Over an 18 month period a total of 222 specimens were tested by both immunofluorescence and the molecular strip. The specimens came from 103 males (median age 3.5 y), 80 females (median age 9 y) and 5 quality assurance scheme specimens. Viruses were recovered from a number of specimen types including broncho-alveolar lavage, nasopharyngeal secretions, sputa, post-mortem lung tissue and combined throat and nasal swabs. Viral detection by IF was poor in sputa and respiratory swabs. A total of 99 viruses were detected in the study from 79 patients and 4 quality control specimens: 31 by immunofluorescence and 99 using the molecular strip. The strip consistently out-performed immunofluorescence with no loss of diagnostic specificity. CONCLUSIONS: The touchdown protocol with pre-dispensed primer master-mixes was suitable for replacing virus culture for the diagnosis of respiratory viruses which were negative by immunofluorescence. Results by immunofluorescence were available after an average of 4–12 hours while molecular strip results were available within 24 hours, considerably faster than viral culture. The combined strip and touchdown protocol proved to be a convenient and reliable method of testing for multiple viruses in a routine setting.",2004 Oct 25,"['Coyle, Peter V', 'Ong, Grace M', ""O'Neill, Hugh J"", 'McCaughey, Conall', 'De Ornellas, Dennis', 'Mitchell, Frederick', 'Mitchell, Suzanne J', 'Feeney, Susan A', 'Wyatt, Dorothy E', 'Forde, Marian', 'Stockton, Joanne']",BMC Microbiol,,,True
8b12db91c31cd4a723270f3cbb56f7919581bb02,PMC,Clinical education of ethicists: the role of a clinical ethics fellowship,http://dx.doi.org/10.1186/1472-6939-5-6,PMC529455,15533244,CC BY,"BACKGROUND: Although clinical ethicists are becoming more prevalent in healthcare settings, their required training and education have not been clearly delineated. Most agree that training and education are important, but their nature and delivery remain topics of debate. One option is through completion of a clinical ethics fellowship. METHOD: In this paper, the first four fellows to complete a newly developed fellowship program discuss their experiences. They describe the goals, structure, participants and activities of the fellowship. They identify key elements for succeeding as a clinical ethicist and sustaining a clinical ethics program. They critically reflect upon the challenges faced in the program. RESULTS: The one-year fellowship provided real-time clinical opportunities that helped them to develop the necessary knowledge and skills, gain insight into the role and scope of practice of clinical ethicists and hone valuable character traits. CONCLUSION: The fellowship enabled each of the fellows to assume confidently and competently a position as a clinical ethicist upon completion.",2004 Nov 8,"['Chidwick, Paula', 'Faith, Karen', 'Godkin, Dianne', 'Hardingham, Laurie']",BMC Med Ethics,,,True
ec3ede6e7539f8a035cf5955a65fa0c9bbb8b3b5,PMC,The Immune Response to Astrovirus Infection,http://dx.doi.org/10.3390/v9010001,PMC5294970,28042824,CC BY,"Astroviruses are one of the leading causes of pediatric gastroenteritis worldwide and are clinically importantly pathogens in the elderly and immunocompromised populations. Although the use of cell culture systems and small animal models have enhanced our understanding of astrovirus infection and pathogenesis, little is known about the immune response to astrovirus infection. Studies from humans and animals suggest that adaptive immunity is important in restricting classic and novel astrovirus infections, while studies from animal models and cell culture systems suggest that an innate immune system plays a role in limiting astrovirus replication. The relative contribution of each arm of the immune system in restricting astrovirus infection remains unknown. This review summarizes our current understanding of the immune response to astrovirus infection and highlights some of the key questions that stem from these studies. A full understanding of the immune response to astrovirus infection is required to be able to treat and control astrovirus-induced gastroenteritis.",2016 Dec 30,"Marvin, Shauna A.",Viruses,,,True
515da9e83a07430922c9fe2a979c0698799aa56c,PMC,Astrovirus Diagnostics,http://dx.doi.org/10.3390/v9010010,PMC5294979,28085120,CC BY,"Various methods exist to detect an astrovirus infection. Current methods include electron microscopy (EM), cell culture, immunoassays, polymerase chain reaction (PCR) and various other molecular approaches that can be applied in the context of diagnostic or in surveillance studies. With the advent of metagenomics, novel human astrovirus (HAstV) strains have been found in immunocompromised individuals in association with central nervous system (CNS) infections. This work reviews the past and current methods for astrovirus detection and their uses in both research laboratories and for medical diagnostic purposes.",2017 Jan 13,"['Pérot, Philippe', 'Lecuit, Marc', 'Eloit, Marc']",Viruses,,,True
a53b809c3b22d019046ee761e05c464bd629079a,PMC,Novel Approach for Isolation and Identification of Porcine Epidemic Diarrhea Virus (PEDV) Strain NJ Using Porcine Intestinal Epithelial Cells,http://dx.doi.org/10.3390/v9010019,PMC5294988,28117718,CC BY,"Porcine epidemic diarrhea virus (PEDV), which is the causative agent of porcine epidemic diarrhea in China and other countries, is responsible for serious economic losses in the pork industry. Inactivated PEDV vaccine plays a key role in controlling the prevalence of PEDV. However, consistently low viral titers are obtained during the propagation of PEDV in vitro; this represents a challenge to molecular analyses of the virus and vaccine development. In this study, we successfully isolated a PEDV isolate (strain NJ) from clinical samples collected during a recent outbreak of diarrhea in piglets in China, using porcine intestinal epithelial cells (IEC). We found that the isolate was better adapted to growth in IECs than in Vero cells, and the titer of the IEC cultures was 10(4.5) TCID(50)/0.1 mL at passage 45. Mutations in the S protein increased with the viral passage and the mutations tended towards attenuation. Viral challenge showed that the survival of IEC-adapted cultures was higher at the 45th passage than at the 5th passage. The use of IECs to isolate and propagate PEDV provides an effective approach for laboratory-based diagnosis of PEDV, as well as studies of the epidemiological characteristics and molecular biology of this virus.",2017 Jan 21,"['Shi, Wen', 'Jia, Shuo', 'Zhao, Haiyuan', 'Yin, Jiyuan', 'Wang, Xiaona', 'Yu, Meiling', 'Ma, Sunting', 'Wu, Yang', 'Chen, Ying', 'Fan, Wenlu', 'Xu, Yigang', 'Li, Yijing']",Viruses,,,True
abcb3cbc5b6ed2707546a1a22fd81724104416ed,PMC,Characterization of the Transcriptome and Gene Expression of Brain Tissue in Sevenband Grouper (Hyporthodus septemfasciatus) in Response to NNV Infection,http://dx.doi.org/10.3390/genes8010031,PMC5295026,28098800,CC BY,"Grouper is one of the favorite sea food resources in Southeast Asia. However, the outbreaks of the viral nervous necrosis (VNN) disease due to nervous necrosis virus (NNV) infection have caused mass mortality of grouper larvae. Many aqua-farms have suffered substantial financial loss due to the occurrence of VNN. To better understand the infection mechanism of NNV, we performed the transcriptome analysis of sevenband grouper brain tissue, the main target of NNV infection. After artificial NNV challenge, transcriptome of brain tissues of sevenband grouper was subjected to next generation sequencing (NGS) using an Illumina Hi-seq 2500 system. Both mRNAs from pooled samples of mock and NNV-infected sevenband grouper brains were sequenced. Clean reads of mock and NNV-infected samples were de novo assembled and obtained 104,348 unigenes. In addition, 628 differentially expressed genes (DEGs) in response to NNV infection were identified. This result could provide critical information not only for the identification of genes involved in NNV infection, but for the understanding of the response of sevenband groupers to NNV infection.",2017 Jan 13,"['Kim, Jong-Oh', 'Kim, Jae-Ok', 'Kim, Wi-Sik', 'Oh, Myung-Joo']",Genes (Basel),,,True
da8a9f50efb758be10b61ea4c5c51cd2fbd004b4,PMC,"Visible Light-Responsive Platinum-Containing Titania Nanoparticle-Mediated Photocatalysis Induces Nucleotide Insertion, Deletion and Substitution Mutations",http://dx.doi.org/10.3390/nano7010002,PMC5295192,28336836,CC BY,"Conventional photocatalysts are primarily stimulated using ultraviolet (UV) light to elicit reactive oxygen species and have wide applications in environmental and energy fields, including self-cleaning surfaces and sterilization. Because UV illumination is hazardous to humans, visible light-responsive photocatalysts (VLRPs) were discovered and are now applied to increase photocatalysis. However, fundamental questions regarding the ability of VLRPs to trigger DNA mutations and the mutation types it elicits remain elusive. Here, through plasmid transformation and β-galactosidase α-complementation analyses, we observed that visible light-responsive platinum-containing titania (TiO(2)) nanoparticle (NP)-mediated photocatalysis considerably reduces the number of Escherichia coli transformants. This suggests that such photocatalytic reactions cause DNA damage. DNA sequencing results demonstrated that the DNA damage comprises three mutation types, namely nucleotide insertion, deletion and substitution; this is the first study to report the types of mutations occurring after photocatalysis by TiO(2)-VLRPs. Our results may facilitate the development and appropriate use of new-generation TiO(2) NPs for biomedical applications.",2016 Dec 28,"['Sun, Der-Shan', 'Tseng, Yao-Hsuan', 'Wu, Wen-Shiang', 'Wong, Ming-Show', 'Chang, Hsin-Hou']",Nanomaterials (Basel),,,True
b29070e205fd519c6abc78e085f500f8271938d3,PMC,"Visible Light-Responsive Platinum-Containing Titania Nanoparticle-Mediated Photocatalysis Induces Nucleotide Insertion, Deletion and Substitution Mutations",http://dx.doi.org/10.3390/nano7010002,PMC5295192,28336836,CC BY,"Conventional photocatalysts are primarily stimulated using ultraviolet (UV) light to elicit reactive oxygen species and have wide applications in environmental and energy fields, including self-cleaning surfaces and sterilization. Because UV illumination is hazardous to humans, visible light-responsive photocatalysts (VLRPs) were discovered and are now applied to increase photocatalysis. However, fundamental questions regarding the ability of VLRPs to trigger DNA mutations and the mutation types it elicits remain elusive. Here, through plasmid transformation and β-galactosidase α-complementation analyses, we observed that visible light-responsive platinum-containing titania (TiO(2)) nanoparticle (NP)-mediated photocatalysis considerably reduces the number of Escherichia coli transformants. This suggests that such photocatalytic reactions cause DNA damage. DNA sequencing results demonstrated that the DNA damage comprises three mutation types, namely nucleotide insertion, deletion and substitution; this is the first study to report the types of mutations occurring after photocatalysis by TiO(2)-VLRPs. Our results may facilitate the development and appropriate use of new-generation TiO(2) NPs for biomedical applications.",2016 Dec 28,"['Sun, Der-Shan', 'Tseng, Yao-Hsuan', 'Wu, Wen-Shiang', 'Wong, Ming-Show', 'Chang, Hsin-Hou']",Nanomaterials (Basel),,,False
daf955dfd5f5ca4e6967e9c1a03904f441d4c319,PMC,Myopericarditis: A Diagnosis of Uncertainty,http://dx.doi.org/10.14740/cr428w,PMC5295574,28197253,CC BY,"Myocarditis can present in many different forms and can be overlooked by more life-threatening conditions. At times it may mimic conditions such as acute myocardial infarction and although it may have features highly suggestive of myocarditis, other etiologies need to be excluded. Thus, due to its clinical presentation, lab findings, and electrocardiogram analysis, it often can be confused with other conditions, making it a diagnostic dilemma of uncertainty. Myopericarditis is normally caused by viral infections, most common of which is coxsackievirus. Here we report a case of a 52-year-old gentleman who presented with a clinical picture of acute myocardial ischemia versus dissection, which overlooked a rather less threatening etiology of myopericarditis.",2015 Oct 25,"['Khan, Rafay', 'Iroka, Nneka', 'Tulpule, Sunil', 'Arshed, Sabrina', 'Ansari, Mohammad', 'Sahgal, Puneet', 'Yousif, Abdalla']",Cardiol Res,,,True
57b4aa7990ee59eb32397dc0dbb4af096a4e9aa8,PMC,Human Enterovirus 68 Interferes with the Host Cell Cycle to Facilitate Viral Production,http://dx.doi.org/10.3389/fcimb.2017.00029,PMC5296350,28229049,CC BY,"Enterovirus D68 (EV-D68) is an emerging pathogen that recently caused a large outbreak of severe respiratory disease in the United States and other countries. Little is known about the relationship between EV-D68 virus and host cells. In this study, we assessed the effect of the host cell cycle on EV-D68 viral production, as well as the ability of EV-D68 to manipulate host cell cycle progression. The results suggest that synchronization in G0/G1 phase, but not S phase, promotes viral production, while synchronization in G2/M inhibits viral production. Both an early EV-D68 isolate and currently circulating strains of EV-D68 can manipulate the host cell cycle to arrest cells in the G0/G1 phase, thus providing favorable conditions for virus production. Cell cycle regulation by EV-D68 was associated with corresponding effects on the expression of cyclins and CDKs, which were observed at the level of the protein and/or mRNA. Furthermore, the viral non-structural protein 3D of EV-D68 prevents progression from G0/G1 to S. Interestingly, another member of the Picornaviridae family, EV-A71, differs from EV-D68 in that G0/G1 synchronization inhibits, rather than promotes, EV-A71 viral replication. However, these viruses are similar in that G2/M synchronization inhibits the production and activity of both viruses, which is suggestive of a common therapeutic target for both types of enterovirus. These results further clarify the pathogenic mechanisms of enteroviruses and provide a potential strategy for the treatment and prevention of EV-D68-related disease.",2017 Feb 8,"['Wang, Zeng-yan', 'Zhong, Ting', 'Wang, Yue', 'Song, Feng-mei', 'Yu, Xiao-feng', 'Xing, Li-ping', 'Zhang, Wen-yan', 'Yu, Jing-hua', 'Hua, Shu-cheng', 'Yu, Xiao-fang']",Front Cell Infect Microbiol,,,True
63c2fc6a6f91490370687f314718221c70e0f9b4,PMC,Malaria from hyperendemicity to elimination in Hekou County on China–Vietnam border: an ecological study,http://dx.doi.org/10.1186/s12936-017-1709-z,PMC5297092,28173802,CC BY,"BACKGROUND: Malaria control and elimination are challenged by diversity and complexity of the determinants on the international border in the Great Mekong Sub-region. Hekou, a Chinese county on the China–Vietnam border, was used to document Chinese experiences and lessons for malaria control and elimination. METHODS: The design was an ecological study. Malaria burden before 1951 and procedures of 64 years (1952–2015) from malaria hyperendemicity to elimination are described. Single and bilinear regression analysis was utilized to analyse the relationship between the annual malaria incidence (AMI) and gross domestic product (GDP), urbanization rate, and banana planting area (BPA). RESULTS: There was a huge malaria burden before 1951. AMI was reduced from 358.62 per 1000 person-years in 1953 to 5.69 per 1000 person-years in 1960. A system of primary health services, comprising three levels of county township hospitals and village health stations maintained malaria control and surveillance activities in changing political and social-economic settings. However, potential under-reported of malaria and market-oriented healthcare led to a malaria epidemic in 1987. Strong political commitment reoriented malaria from a control to an elimination programme. High coverage of malaria intervention and population access to intervention was crucial for malaria control and elimination; meanwhile, AMI was closely associated with socio-economic development, correlation coefficients (R) −0.6845 (95% CI −0.7978, −0.6845) for national GDP, −0.7014 (−0.8093, −0.7014) for national urbanization rate and −0.5563 (−0.7147, −0.3437) for BPA. CONCLUSIONS: Multifactor, including political commitment, effective interventions, social and economic development and changing ecological environment, and the complicated interactions between these factors contribute to malaria elimination in Hekou County. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-017-1709-z) contains supplementary material, which is available to authorized users.",2017 Feb 7,"['Xu, Jian-Wei', 'Li, Jian-Jie', 'Guo, Hong-Ping', 'Pu, Shu-Wei', 'Li, Shu-Mei', 'Wang, Rong-Hua', 'Liu, Hui', 'Wang, Wei-Jia']",Malar J,,,True
4b3de92b03457bddd57edad106262751d712c528,PMC,Reverse Genetics Approaches for the Development of Influenza Vaccines,http://dx.doi.org/10.3390/ijms18010020,PMC5297655,28025504,CC BY,"Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines.",2016 Dec 22,"['Nogales, Aitor', 'Martínez-Sobrido, Luis']",Int J Mol Sci,,,True
d4f4ca21b787bb6a090b859a21aade4e7a0fb633,PMC,Immunological aspects of the efficiency of protectotype vaccination strategy against chicken infectious bronchitis,http://dx.doi.org/10.1186/s12917-017-0963-1,PMC5299672,28178957,CC BY,"BACKGROUND: One of the most commonly applied protectotype vaccination protocol against infectious bronchitis (IB) in broiler chickens in the EU is simultaneous or alternate use of Ma5 and 4/91 vaccine strains. After IB vaccination and infection, systemic and upper respiratory tract (URT), humoral and cell-mediated immunity (CMI), are stimulated. The level of this stimulation correlates with the level of protection against IB. RESULTS: We’ve investigated the development of URT and systemic, cell-mediated and humoral immunity in commercial broiler chickens vaccinated with Ma5 and/or 4/91 strains at hatch day. We’ve demonstrated that the group vaccinated with Ma5 and 4/91 strain simultaneously developed the most desirable immunity which reflects the level of CD8(+) T cells stimulation in spleen and Harderian gland, as well as the level of IgA and IgY in URT washings and serum and their cross-reactivity with 7 IBV strains. CONCLUSIONS: Although we did not demonstrate directly why Ma5 + 4/91 protocol is so efficient it seems that it combines the benefits of monovalent vaccination with either Ma5 or 4/91 and while Ma5 seems to stimulate CMI more efficiently, the 4/91 strain generates a wider spectrum of immune system cross-reactivity and higher URT IgA production.",2017 Feb 8,"['Smialek, Marcin', 'Tykalowski, Bartlomiej', 'Dziewulska, Daria', 'Stenzel, Tomasz', 'Koncicki, Andrzej']",BMC Vet Res,,,True
74badd024e394563add31baf5ec9d6fde58a43f3,PMC,Global research trends of World Health Organization’s top eight emerging pathogens,http://dx.doi.org/10.1186/s12992-017-0233-9,PMC5299748,28179007,CC BY,"BACKGROUND: On December 8(th), 2015, World Health Organization published a priority list of eight pathogens expected to cause severe outbreaks in the near future. To better understand global research trends and characteristics of publications on these emerging pathogens, we carried out this bibliometric study hoping to contribute to global awareness and preparedness toward this topic. METHOD: Scopus database was searched for the following pathogens/infectious diseases: Ebola, Marburg, Lassa, Rift valley, Crimean-Congo, Nipah, Middle Eastern Respiratory Syndrome (MERS), and Severe Respiratory Acute Syndrome (SARS). Retrieved articles were analyzed to obtain standard bibliometric indicators. RESULTS: A total of 8619 journal articles were retrieved. Authors from 154 different countries contributed to publishing these articles. Two peaks of publications, an early one for SARS and a late one for Ebola, were observed. Retrieved articles received a total of 221,606 citations with a mean ± standard deviation of 25.7 ± 65.4 citations per article and an h-index of 173. International collaboration was as high as 86.9%. The Centers for Disease Control and Prevention had the highest share (344; 5.0%) followed by the University of Hong Kong with 305 (4.5%). The top leading journal was Journal of Virology with 572 (6.6%) articles while Feldmann, Heinz R. was the most productive researcher with 197 (2.3%) articles. China ranked first on SARS, Turkey ranked first on Crimean-Congo fever, while the United States of America ranked first on the remaining six diseases. Of retrieved articles, 472 (5.5%) were on vaccine – related research with Ebola vaccine being most studied. CONCLUSION: Number of publications on studied pathogens showed sudden dramatic rise in the past two decades representing severe global outbreaks. Contribution of a large number of different countries and the relatively high h-index are indicative of how international collaboration can create common health agenda among distant different countries.",2017 Feb 8,"Sweileh, Waleed M.",Global Health,,,True
db11eb7515dfdc25067ed42a819b723982da41ae,PMC,Human rights violations in organ procurement practice in China,http://dx.doi.org/10.1186/s12910-017-0169-x,PMC5299785,28178953,CC BY,"BACKGROUND: Over 90% of the organs transplanted in China before 2010 were procured from prisoners. Although Chinese officials announced in December 2014 that the country would completely cease using organs harvested from prisoners, no regulatory adjustments or changes in China’s organ donation laws followed. As a result, the use of prisoner organs remains legal in China if consent is obtained. DISCUSSION: We have collected and analysed available evidence on human rights violations in the organ procurement practice in China. We demonstrate that the practice not only violates international ethics standards, it is also associated with a large scale neglect of fundamental human rights. This includes organ procurement without consent from prisoners or their families as well as procurement of organs from incompletely executed, still-living prisoners. The human rights critique of these practices will also address the specific situatedness of prisoners, often conditioned and traumatized by a cascade of human rights abuses in judicial structures. CONCLUSION: To end the unethical practice and the abuse associated with it, we suggest to inextricably bind the use of human organs procured in the Chinese transplant system to enacting Chinese legislation prohibiting the use of organs from executed prisoners and making explicit rules for law enforcement. Other than that, the international community must cease to abet the continuation of the present system by demanding an authoritative ban on the use of organs from executed Chinese prisoners. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12910-017-0169-x) contains supplementary material, which is available to authorized users.",2017 Feb 8,"['Paul, Norbert W.', 'Caplan, Arthur', 'Shapiro, Michael E.', 'Els, Charl', 'Allison, Kirk C.', 'Li, Huige']",BMC Med Ethics,,,False
a9348f9a4519219e9f2adfab6e093b66f4ee3131,PMC,Human rights violations in organ procurement practice in China,http://dx.doi.org/10.1186/s12910-017-0169-x,PMC5299785,28178953,CC BY,"BACKGROUND: Over 90% of the organs transplanted in China before 2010 were procured from prisoners. Although Chinese officials announced in December 2014 that the country would completely cease using organs harvested from prisoners, no regulatory adjustments or changes in China’s organ donation laws followed. As a result, the use of prisoner organs remains legal in China if consent is obtained. DISCUSSION: We have collected and analysed available evidence on human rights violations in the organ procurement practice in China. We demonstrate that the practice not only violates international ethics standards, it is also associated with a large scale neglect of fundamental human rights. This includes organ procurement without consent from prisoners or their families as well as procurement of organs from incompletely executed, still-living prisoners. The human rights critique of these practices will also address the specific situatedness of prisoners, often conditioned and traumatized by a cascade of human rights abuses in judicial structures. CONCLUSION: To end the unethical practice and the abuse associated with it, we suggest to inextricably bind the use of human organs procured in the Chinese transplant system to enacting Chinese legislation prohibiting the use of organs from executed prisoners and making explicit rules for law enforcement. Other than that, the international community must cease to abet the continuation of the present system by demanding an authoritative ban on the use of organs from executed Chinese prisoners. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12910-017-0169-x) contains supplementary material, which is available to authorized users.",2017 Feb 8,"['Paul, Norbert W.', 'Caplan, Arthur', 'Shapiro, Michael E.', 'Els, Charl', 'Allison, Kirk C.', 'Li, Huige']",BMC Med Ethics,,,True
d80ebadc0c335da9a5c4fffa527690bf146e934d,PMC,Rapid and sensitive real-time assay for the detection of respiratory syncytial virus using RT-SIBA®,http://dx.doi.org/10.1186/s12879-017-2227-x,PMC5301360,28183291,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is one of the most common causes of respiratory tract infections among young children and the elderly. Timely and accurate diagnosis of respiratory tract infections improves patient care and minimizes unnecessary prescriptions of antibiotics. We sought to develop a rapid nucleic acid tests for the detection of RSV within minutes, while retaining the high sensitivity achieved with RT-PCR. METHODS: We developed and evaluated a reverse transcription isothermal nucleic acid amplification method, reverse transcription strand invasion based amplification (RT-SIBA), for the rapid detection of RSV. RESULTS: The developed RT-SIBA assay showed good sensitivity by detecting as few as 10 copies of RSV RNA within 20 min compared with reverse transcription polymerase chain reaction, which took approximately 2 h. The performance of the RT-SIBA RSV assay was further investigated using nasopharyngeal swab specimens. The RT-SIBA assay had a sensitivity of 100% (25/25) and a specificity of 100% (15/15). CONCLUSION: RT-SIBA did not require highly purified RNA for the rapid detection of RSV and was therefore compatible with rapid specimen processing methods. This reduces the complexity of specimen preparation and further shortens the total amount of time needed to detect RSV in clinical specimens. The developed RT-SIBA assay for RSV could be a useful tool for prompt management of this infection",2017 Feb 10,"['Eboigbodin, Kevin E.', 'Moilanen, Kirsi', 'Elf, Sonja', 'Hoser, Mark']",BMC Infect Dis,,,True
43918c75d7b7d3f9402b1342dfea1e19eb2bd909,PMC,Antibacterial Properties of Visible-Light-Responsive Carbon-Containing Titanium Dioxide Photocatalytic Nanoparticles against Anthrax,http://dx.doi.org/10.3390/nano6120237,PMC5302719,28335365,CC BY,"The bactericidal activity of conventional titanium dioxide (TiO(2)) photocatalyst is effective only on irradiation by ultraviolet light, which restricts the applications of TiO(2) for use in living environments. Recently, carbon-containing TiO(2) nanoparticles [TiO(2)(C) NP] were found to be a visible-light-responsive photocatalyst (VLRP), which displayed significantly enhanced antibacterial properties under visible light illumination. However, whether TiO(2)(C) NPs exert antibacterial properties against Bacillus anthracis remains elusive. Here, we evaluated these VLRP NPs in the reduction of anthrax-induced pathogenesis. Bacteria-killing experiments indicated that a significantly higher proportion (40%–60%) of all tested Bacillus species, including B. subtilis, B. cereus, B. thuringiensis, and B. anthracis, were considerably eliminated by TiO(2)(C) NPs. Toxin inactivation analysis further suggested that the TiO(2)(C) NPs efficiently detoxify approximately 90% of tested anthrax lethal toxin, a major virulence factor of anthrax. Notably, macrophage clearance experiments further suggested that, even under suboptimal conditions without considerable bacterial killing, the TiO(2)(C) NP-mediated photocatalysis still exhibited antibacterial properties through the reduction of bacterial resistance against macrophage killing. Our results collectively suggested that TiO(2)(C) NP is a conceptually feasible anti-anthrax material, and the relevant technologies described herein may be useful in the development of new strategies against anthrax.",2016 Dec 9,"['Sun, Der-Shan', 'Kau, Jyh-Hwa', 'Huang, Hsin-Hsien', 'Tseng, Yao-Hsuan', 'Wu, Wen-Shiang', 'Chang, Hsin-Hou']",Nanomaterials (Basel),,,True
6de6302336946d92dfdf1e1ec1c573a2299f195c,PMC,Polyprenyl Immunostimulant Treatment of Cats with Presumptive Non-Effusive Feline Infectious Peritonitis In a Field Study,http://dx.doi.org/10.3389/fvets.2017.00007,PMC5306384,28261584,CC BY,"Feline infectious peritonitis (FIP) is a fatal disease with no clinically effective treatment. This field study evaluated treatment with Polyprenyl Immunostimulant (PI) in cats with the non-effusive form of FIP. Because immune suppression is a major component in the pathology of FIP, we hypothesized that treatment with an immune system stimulant would increase survival times of cats with dry FIP. Sixty cats, diagnosed with dry FIP by primary care and specialist veterinarians and meeting the acceptance criteria, were treated with PI without intentional selection of less severe cases. The survival time from the start of PI treatment in cats diagnosed with dry FIP showed that of the 60 cats with dry FIP treated with PI, 8 survived over 200 days, and 4 of 60 survived over 300 days. A literature search identified 59 cats with non-effusive or dry FIP; no cat with only dry FIP lived longer than 200 days. Veterinarians of cats treated with PI that survived over 30 days reported improvements in clinical signs and behavior. The survival times in our study were significantly longer in cats who were not treated with corticosteroids concurrently with PI. While not a cure, PI shows promise in the treatment of dry form FIP, but a controlled study will be needed to verify the benefit.",2017 Feb 14,"['Legendre, Alfred M.', 'Kuritz, Tanya', 'Galyon, Gina', 'Baylor, Vivian M.', 'Heidel, Robert Eric']",Front Vet Sci,,,True
af547c43638857c71c035fa4217e167f681f837c,PMC,Effective inhibition of MERS-CoV infection by resveratrol,http://dx.doi.org/10.1186/s12879-017-2253-8,PMC5307780,28193191,CC BY,"BACKGROUND: Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging viral pathogen that causes severe morbidity and mortality. Up to date, there is no approved or licensed vaccine or antiviral medicines can be used to treat MERS-CoV-infected patients. Here, we analyzed the antiviral activities of resveratrol, a natural compound found in grape seeds and skin and in red wine, against MERS-CoV infection. METHODS: We performed MTT and neutral red uptake assays to assess the survival rates of MERS-infected Vero E6 cells. In addition, quantitative PCR, western blotting, and immunofluorescent assays determined the intracellular viral RNA and protein expression. For viral productivity, we utilized plaque assays to confirm the antiviral properties of resveratrol against MERS-CoV. RESULTS: Resveratrol significantly inhibited MERS-CoV infection and prolonged cellular survival after virus infection. We also found that the expression of nucleocapsid (N) protein essential for MERS-CoV replication was decreased after resveratrol treatment. Furthermore, resveratrol down-regulated the apoptosis induced by MERS-CoV in vitro. By consecutive administration of resveratrol, we were able to reduce the concentration of resveratrol while achieving inhibitory effectiveness against MERS-CoV. CONCLUSION: In this study, we first demonstrated that resveratrol is a potent anti-MERS agent in vitro. We perceive that resveratrol can be a potential antiviral agent against MERS-CoV infection in the near future.",2017 Feb 13,"['Lin, Shih-Chao', 'Ho, Chi-Tang', 'Chuo, Wen-Ho', 'Li, Shiming', 'Wang, Tony T.', 'Lin, Chi-Chen']",BMC Infect Dis,,,True
c923009c37cf93d35e69ec161afaf3cc334e03a7,PMC,Viral aetiology of bronchiolitis in hospitalised children in Qatar,http://dx.doi.org/10.1186/s12879-017-2225-z,PMC5307797,28193180,CC BY,"BACKGROUND: Bronchiolitis is considered one of the earliest and most common causes of hospitalisation in young children. Development of molecular technologies allowed a better understanding of bronchiolitis aetiology. Results from cohort studies evaluating the association between single, multiple viral infections and clinical outcomes are conflicting. Data on viral bronchiolitis in children were found to be limited in Qatar. This study aimed to determine frequency and seasonal trends of viral pathogens causing acute bronchiolitis, and to explore association between viral pathogens, disease severity and length of stay (LOS). METHODS: This is a retrospective descriptive study, including children admitted in 2010 and 2011 with acute bronchiolitis. Presenting history, physical examination and respiratory viral co-infections as detected by molecular assays were analysed. RESULTS: At least one virus was detected in 315/369 (85.4%) of included children with single and multiple viruses in 67 and 33% of cases respectively. Respiratory syncytial virus (RSV) was the most detected virus, accounting for 51.2% followed by rhinovirus (RV) in 25.5% of cases. Fall and summer admissions were associated with longer LOS. On multivariate logistic regression analysis, retraction (OR 3.96; 95% CI 1.64,9.59) and age group 1–3 months (OR 3.09; 95% CI 1.06,9.05) were associated with longer LOS. Crepitation (OR 9.15; 95% CI 1.58,53.13), retraction (OR 4.10; 95% CI 1.05,16.12) and respiratory rate (OR 1.46; 95% CI 1.28,1.66) were associated with moderate to severe bronchiolitis. Identifying the viral agent did not influence disease severity or LOS. CONCLUSION: Clinical presentation is of more relevance to LOS and disease severity than the detected viruses. Future studies should investigate the interplay between climate characteristics, population’s factors and the most detectable circulating viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-017-2225-z) contains supplementary material, which is available to authorized users.",2017 Feb 13,"['Janahi, Ibrahim', 'Abdulkayoum, Anas', 'Almeshwesh, Fawziya', 'Alkuwari, Mohamed', 'Al hammadi, Ahmed', 'Alameri, Marwah']",BMC Infect Dis,,,True
27ac134e8e678f379d1550477ea87257c9c2ed2a,PMC,Metagenomic Sequencing for Surveillance of Food- and Waterborne Viral Diseases,http://dx.doi.org/10.3389/fmicb.2017.00230,PMC5309255,28261185,CC BY,"A plethora of viruses can be transmitted by the food- and waterborne route. However, their recognition is challenging because of the variety of viruses, heterogeneity of symptoms, the lack of awareness of clinicians, and limited surveillance efforts. Classical food- and waterborne viral disease outbreaks are mainly caused by caliciviruses, but the source of the virus is often not known and the foodborne mode of transmission is difficult to discriminate from human-to-human transmission. Atypical food- and waterborne viral disease can be caused by viruses such as hepatitis A and hepatitis E. In addition, a source of novel emerging viruses with a potential to spread via the food- and waterborne route is the repeated interaction of humans with wildlife. Wildlife-to-human adaptation may give rise to self- limiting outbreaks in some cases, but when fully adjusted to the human host can be devastating. Metagenomic sequencing has been investigated as a promising solution for surveillance purposes as it detects all viruses in a single protocol, delivers additional genomic information for outbreak tracing, and detects novel unknown viruses. Nevertheless, several issues must be addressed to apply metagenomic sequencing in surveillance. First, sample preparation is difficult since the genomic material of viruses is generally overshadowed by host- and bacterial genomes. Second, several data analysis issues hamper the efficient, robust, and automated processing of metagenomic data. Third, interpretation of metagenomic data is hard, because of the lack of general knowledge of the virome in the food chain and the environment. Further developments in virus-specific nucleic acid extraction methods, bioinformatic data processing applications, and unifying data visualization tools are needed to gain insightful surveillance knowledge from suspect food samples.",2017 Feb 15,"['Nieuwenhuijse, David F.', 'Koopmans, Marion P. G.']",Front Microbiol,,,True
1cedf8c2a09236302e9b5717604bdb98bae977ff,PMC,The Baltic Sea Virome: Diversity and Transcriptional Activity of DNA and RNA Viruses,http://dx.doi.org/10.1128/mSystems.00125-16,PMC5309335,28217745,CC BY,"Metagenomic and metatranscriptomic data were generated from size-fractionated samples from 11 sites within the Baltic Sea and adjacent marine waters of Kattegat and freshwater Lake Torneträsk in order to investigate the diversity, distribution, and transcriptional activity of virioplankton. Such a transect, spanning a salinity gradient from freshwater to the open sea, facilitated a broad genome-enabled investigation of natural as well as impacted aspects of Baltic Sea viral communities. Taxonomic signatures representative of phages within the widely distributed order Caudovirales were identified with enrichments in lesser-known families such as Podoviridae and Siphoviridae. The distribution of phage reported to infect diverse and ubiquitous heterotrophic bacteria (SAR11 clades) and cyanobacteria (Synechococcus sp.) displayed population-level shifts in diversity. Samples from higher-salinity conditions (>14 practical salinity units [PSU]) had increased abundances of viruses for picoeukaryotes, i.e., Ostreococcus. These data, combined with host diversity estimates, suggest viral modulation of diversity on the whole-community scale, as well as in specific prokaryotic and eukaryotic lineages. RNA libraries revealed single-stranded DNA (ssDNA) and RNA viral populations throughout the Baltic Sea, with ssDNA phage highly represented in Lake Torneträsk. Further, our data suggest relatively high transcriptional activity of fish viruses within diverse families known to have broad host ranges, such as Nodoviridae (RNA), Iridoviridae (DNA), and predicted zoonotic viruses that can cause ecological and economic damage as well as impact human health. IMPORTANCE Inferred virus-host relationships, community structures of ubiquitous ecologically relevant groups, and identification of transcriptionally active populations have been achieved with our Baltic Sea study. Further, these data, highlighting the transcriptional activity of viruses, represent one of the more powerful uses of omics concerning ecosystem health. The use of omics-related data to assess ecosystem health holds great promise for rapid and relatively inexpensive determination of perturbations and risk, explicitly with regard to viral assemblages, as no single marker gene is suitable for widespread taxonomic coverage.",2017 Feb 14,"['Zeigler Allen, Lisa', 'McCrow, John P.', 'Ininbergs, Karolina', 'Dupont, Christopher L.', 'Badger, Jonathan H.', 'Hoffman, Jeffery M.', 'Ekman, Martin', 'Allen, Andrew E.', 'Bergman, Birgitta', 'Venter, J. Craig']",mSystems,,,True
ccad13074c662c83227a86fbe355e5affa7740a6,PMC,The Baltic Sea Virome: Diversity and Transcriptional Activity of DNA and RNA Viruses,http://dx.doi.org/10.1128/mSystems.00125-16,PMC5309335,28217745,CC BY,"Metagenomic and metatranscriptomic data were generated from size-fractionated samples from 11 sites within the Baltic Sea and adjacent marine waters of Kattegat and freshwater Lake Torneträsk in order to investigate the diversity, distribution, and transcriptional activity of virioplankton. Such a transect, spanning a salinity gradient from freshwater to the open sea, facilitated a broad genome-enabled investigation of natural as well as impacted aspects of Baltic Sea viral communities. Taxonomic signatures representative of phages within the widely distributed order Caudovirales were identified with enrichments in lesser-known families such as Podoviridae and Siphoviridae. The distribution of phage reported to infect diverse and ubiquitous heterotrophic bacteria (SAR11 clades) and cyanobacteria (Synechococcus sp.) displayed population-level shifts in diversity. Samples from higher-salinity conditions (>14 practical salinity units [PSU]) had increased abundances of viruses for picoeukaryotes, i.e., Ostreococcus. These data, combined with host diversity estimates, suggest viral modulation of diversity on the whole-community scale, as well as in specific prokaryotic and eukaryotic lineages. RNA libraries revealed single-stranded DNA (ssDNA) and RNA viral populations throughout the Baltic Sea, with ssDNA phage highly represented in Lake Torneträsk. Further, our data suggest relatively high transcriptional activity of fish viruses within diverse families known to have broad host ranges, such as Nodoviridae (RNA), Iridoviridae (DNA), and predicted zoonotic viruses that can cause ecological and economic damage as well as impact human health. IMPORTANCE Inferred virus-host relationships, community structures of ubiquitous ecologically relevant groups, and identification of transcriptionally active populations have been achieved with our Baltic Sea study. Further, these data, highlighting the transcriptional activity of viruses, represent one of the more powerful uses of omics concerning ecosystem health. The use of omics-related data to assess ecosystem health holds great promise for rapid and relatively inexpensive determination of perturbations and risk, explicitly with regard to viral assemblages, as no single marker gene is suitable for widespread taxonomic coverage.",2017 Feb 14,"['Zeigler Allen, Lisa', 'McCrow, John P.', 'Ininbergs, Karolina', 'Dupont, Christopher L.', 'Badger, Jonathan H.', 'Hoffman, Jeffery M.', 'Ekman, Martin', 'Allen, Andrew E.', 'Bergman, Birgitta', 'Venter, J. Craig']",mSystems,,,False
c0afcaab27d3532f3396316eb529468097bd6de7,PMC,TNF Blockade Maintains an IL-10(+) Phenotype in Human Effector CD4(+) and CD8(+) T Cells,http://dx.doi.org/10.3389/fimmu.2017.00157,PMC5309392,28261215,CC BY,"CD4(+) and CD8(+) effector T cell subpopulations can display regulatory potential characterized by expression of the prototypically anti-inflammatory cytokine IL-10. However, the underlying cellular mechanisms that regulate expression of IL-10 in different T cell subpopulations are not yet fully elucidated. We recently showed that TNF inhibitors (TNFi) promote IL-10 expression in human CD4(+) T cells, including IL-17(+) CD4(+) T cells. Here, we further characterized the regulation of IL-10 expression via blockade of TNF signaling or other cytokine/co-stimulatory pathways, in human T cell subpopulations. Addition of the TNFi drug adalimumab to anti-CD3-stimulated human CD4(+) T cell/monocyte cocultures led to increased percentages of IL-10(+) cells in pro-inflammatory IL-17(+), IFNγ(+), TNFα(+), GM-CSF(+), and IL-4(+) CD4(+) T cell subpopulations. Conversely, exogenous TNFα strongly decreased IL-10(+) cell frequencies. TNF blockade also regulated IL-10 expression in CD4(+) T cells upon antigenic stimulation. Using time course experiments in whole peripheral blood mononuclear cell (PBMC) cultures, we show that TNF blockade maintained, rather than increased, IL-10(+) cell frequencies in both CD4(+) and CD8(+) T cells following in vitro stimulation in a dose- and time-dependent manner. Blockade of IL-17, IFNγ, IL-6R, or CD80/CD86-mediated co-stimulation did not significantly regulate IL-10 expression within CD4(+) or CD8(+) T cell subpopulations. We show that TNF blockade acts directly on effector CD4(+) T cells, in the absence of monocytes or CD4(+) CD25(high)CD127(low) regulatory T cells and independently of IL-27, resulting in higher IL-10(+) frequencies after 3 days in culture. IL-10/IL-10R blockade reduced the frequency of IL-10-expressing cells both in the presence and absence of TNF blockade. Addition of recombinant IL-10 alone was insufficient to drive an increase in IL-10(+) CD4(+) T cell frequencies in 3-day CD4(+) T cell/monocyte cocultures, but resulted in increased IL-10 expression at later time points in whole PBMC cultures. Together, these data provide additional insights into the regulation of IL-10 expression in human T cells by TNF blockade. The maintenance of an IL-10(+) phenotype across a broad range of effector T cell subsets may represent an underappreciated mechanism of action underlying this widely used therapeutic strategy.",2017 Feb 15,"['Roberts, Ceri A.', 'Durham, Lucy E.', 'Fleskens, Veerle', 'Evans, Hayley G.', 'Taams, Leonie S.']",Front Immunol,,,True
3de646ee7ce9f4e4b44d204ab15b3f1853fa8b09,PMC,TNF Blockade Maintains an IL-10(+) Phenotype in Human Effector CD4(+) and CD8(+) T Cells,http://dx.doi.org/10.3389/fimmu.2017.00157,PMC5309392,28261215,CC BY,"CD4(+) and CD8(+) effector T cell subpopulations can display regulatory potential characterized by expression of the prototypically anti-inflammatory cytokine IL-10. However, the underlying cellular mechanisms that regulate expression of IL-10 in different T cell subpopulations are not yet fully elucidated. We recently showed that TNF inhibitors (TNFi) promote IL-10 expression in human CD4(+) T cells, including IL-17(+) CD4(+) T cells. Here, we further characterized the regulation of IL-10 expression via blockade of TNF signaling or other cytokine/co-stimulatory pathways, in human T cell subpopulations. Addition of the TNFi drug adalimumab to anti-CD3-stimulated human CD4(+) T cell/monocyte cocultures led to increased percentages of IL-10(+) cells in pro-inflammatory IL-17(+), IFNγ(+), TNFα(+), GM-CSF(+), and IL-4(+) CD4(+) T cell subpopulations. Conversely, exogenous TNFα strongly decreased IL-10(+) cell frequencies. TNF blockade also regulated IL-10 expression in CD4(+) T cells upon antigenic stimulation. Using time course experiments in whole peripheral blood mononuclear cell (PBMC) cultures, we show that TNF blockade maintained, rather than increased, IL-10(+) cell frequencies in both CD4(+) and CD8(+) T cells following in vitro stimulation in a dose- and time-dependent manner. Blockade of IL-17, IFNγ, IL-6R, or CD80/CD86-mediated co-stimulation did not significantly regulate IL-10 expression within CD4(+) or CD8(+) T cell subpopulations. We show that TNF blockade acts directly on effector CD4(+) T cells, in the absence of monocytes or CD4(+) CD25(high)CD127(low) regulatory T cells and independently of IL-27, resulting in higher IL-10(+) frequencies after 3 days in culture. IL-10/IL-10R blockade reduced the frequency of IL-10-expressing cells both in the presence and absence of TNF blockade. Addition of recombinant IL-10 alone was insufficient to drive an increase in IL-10(+) CD4(+) T cell frequencies in 3-day CD4(+) T cell/monocyte cocultures, but resulted in increased IL-10 expression at later time points in whole PBMC cultures. Together, these data provide additional insights into the regulation of IL-10 expression in human T cells by TNF blockade. The maintenance of an IL-10(+) phenotype across a broad range of effector T cell subsets may represent an underappreciated mechanism of action underlying this widely used therapeutic strategy.",2017 Feb 15,"['Roberts, Ceri A.', 'Durham, Lucy E.', 'Fleskens, Veerle', 'Evans, Hayley G.', 'Taams, Leonie S.']",Front Immunol,,,False
71788152b25d71db652985de1cc4fb0513873969,PMC,The Role of Type III Interferons in Hepatitis C Virus Infection and Therapy,http://dx.doi.org/10.1155/2017/7232361,PMC5309426,28255563,CC BY,"The human interferon (IFN) response is a key innate immune mechanism to fight virus infection. IFNs are host-encoded secreted proteins, which induce IFN-stimulated genes (ISGs) with antiviral properties. Among the three classes of IFNs, type III IFNs, also called IFN lambdas (IFNLs), are an essential component of the innate immune response to hepatitis C virus (HCV). In particular, human polymorphisms in IFNL gene loci correlate with hepatitis C disease progression and with treatment response. To date, the underlying mechanisms remain mostly elusive; however it seems clear that viral infection of the liver induces IFNL responses. As IFNL receptors show a more restricted tissue expression than receptors for other classes of IFNs, IFNL treatment has reduced side effects compared to the classical type I IFN treatment. In HCV therapy, however, IFNL will likely not play an important role as highly effective direct acting antivirals (DAA) exist. Here, we will review our current knowledge on IFNL gene expression, protein properties, signaling, ISG induction, and its implications on HCV infection and treatment. Finally, we will discuss the lessons learnt from the HCV and IFNL field for virus infections beyond hepatitis C.",2017 Feb 1,"['Bruening, Janina', 'Weigel, Bettina', 'Gerold, Gisa']",J Immunol Res,,,True
33d625384797e80011cbce651db7f24cab8a13d9,PMC,Preventive behaviors by the level of perceived infection sensitivity during the Korea outbreak of Middle East Respiratory Syndrome in 2015,http://dx.doi.org/10.4178/epih.e2016051,PMC5309729,28092927,CC BY,"OBJECTIVES: This study was performed to investigate the relationship between community residents’ infection sensitivity and their levels of preventive behaviors during the 2015 Middle East Respiratory Syndrome (MERS) outbreak in Korea. METHODS: Seven thousands two hundreds eighty one participants from nine areas in Gyeonggi-do including Pyeongtaek, the origin of the outbreak in 2015 agreed to participate in the survey and the data from 6,739 participants were included in the final analysis. The data on the perceived infection sensitivity were subjected to cluster analysis. The levels of stress, reliability/practice of preventive behaviors, hand washing practice and policy credibility during the outbreak period were analyzed for each cluster. RESULTS: Cluster analysis of infection sensitivity due to the MERS outbreak resulted in classification of participants into four groups: the non-sensitive group (14.5%), social concern group (17.4%), neutral group (29.1%), and overall sensitive group (39.0%). A logistic regression analysis found that the overall sensitive group with high sensitivity had higher stress levels (17.80; 95% confidence interval [CI], 13.77 to 23.00), higher reliability on preventive behaviors (5.81; 95% CI, 4.84 to 6.98), higher practice of preventive behaviors (4.53; 95% CI, 3.83 to 5.37) and higher practice of hand washing (2.71; 95% CI, 2.13 to 3.43) during the outbreak period, compared to the non-sensitive group. CONCLUSIONS: Infection sensitivity of community residents during the MERS outbreak correlated with gender, age, occupation, and health behaviors. When there is an outbreak in the community, there is need to maintain a certain level of sensitivity while reducing excessive stress, as well as promote the practice of preventive behaviors among local residents. In particular, target groups need to be notified and policies need to be established with a consideration of the socio-demographic characteristics of the community.",2016 Nov 16,"['Lee, Soon Young', 'Yang, Hee Jeong', 'Kim, Gawon', 'Cheong, Hae-Kwan', 'Choi, Bo Youl']",Epidemiol Health,,,False
17d92d371f5552921b86de6fb6cd7e65344ddb2e,PMC,Preventive behaviors by the level of perceived infection sensitivity during the Korea outbreak of Middle East Respiratory Syndrome in 2015,http://dx.doi.org/10.4178/epih.e2016051,PMC5309729,28092927,CC BY,"OBJECTIVES: This study was performed to investigate the relationship between community residents’ infection sensitivity and their levels of preventive behaviors during the 2015 Middle East Respiratory Syndrome (MERS) outbreak in Korea. METHODS: Seven thousands two hundreds eighty one participants from nine areas in Gyeonggi-do including Pyeongtaek, the origin of the outbreak in 2015 agreed to participate in the survey and the data from 6,739 participants were included in the final analysis. The data on the perceived infection sensitivity were subjected to cluster analysis. The levels of stress, reliability/practice of preventive behaviors, hand washing practice and policy credibility during the outbreak period were analyzed for each cluster. RESULTS: Cluster analysis of infection sensitivity due to the MERS outbreak resulted in classification of participants into four groups: the non-sensitive group (14.5%), social concern group (17.4%), neutral group (29.1%), and overall sensitive group (39.0%). A logistic regression analysis found that the overall sensitive group with high sensitivity had higher stress levels (17.80; 95% confidence interval [CI], 13.77 to 23.00), higher reliability on preventive behaviors (5.81; 95% CI, 4.84 to 6.98), higher practice of preventive behaviors (4.53; 95% CI, 3.83 to 5.37) and higher practice of hand washing (2.71; 95% CI, 2.13 to 3.43) during the outbreak period, compared to the non-sensitive group. CONCLUSIONS: Infection sensitivity of community residents during the MERS outbreak correlated with gender, age, occupation, and health behaviors. When there is an outbreak in the community, there is need to maintain a certain level of sensitivity while reducing excessive stress, as well as promote the practice of preventive behaviors among local residents. In particular, target groups need to be notified and policies need to be established with a consideration of the socio-demographic characteristics of the community.",2016 Nov 16,"['Lee, Soon Young', 'Yang, Hee Jeong', 'Kim, Gawon', 'Cheong, Hae-Kwan', 'Choi, Bo Youl']",Epidemiol Health,,,True
92f0c7d4162cc1e3f14fedc93005067f30e0c14e,PMC,Preventive behaviors by the level of perceived infection sensitivity during the Korea outbreak of Middle East Respiratory Syndrome in 2015,http://dx.doi.org/10.4178/epih.e2016051,PMC5309729,28092927,CC BY,"OBJECTIVES: This study was performed to investigate the relationship between community residents’ infection sensitivity and their levels of preventive behaviors during the 2015 Middle East Respiratory Syndrome (MERS) outbreak in Korea. METHODS: Seven thousands two hundreds eighty one participants from nine areas in Gyeonggi-do including Pyeongtaek, the origin of the outbreak in 2015 agreed to participate in the survey and the data from 6,739 participants were included in the final analysis. The data on the perceived infection sensitivity were subjected to cluster analysis. The levels of stress, reliability/practice of preventive behaviors, hand washing practice and policy credibility during the outbreak period were analyzed for each cluster. RESULTS: Cluster analysis of infection sensitivity due to the MERS outbreak resulted in classification of participants into four groups: the non-sensitive group (14.5%), social concern group (17.4%), neutral group (29.1%), and overall sensitive group (39.0%). A logistic regression analysis found that the overall sensitive group with high sensitivity had higher stress levels (17.80; 95% confidence interval [CI], 13.77 to 23.00), higher reliability on preventive behaviors (5.81; 95% CI, 4.84 to 6.98), higher practice of preventive behaviors (4.53; 95% CI, 3.83 to 5.37) and higher practice of hand washing (2.71; 95% CI, 2.13 to 3.43) during the outbreak period, compared to the non-sensitive group. CONCLUSIONS: Infection sensitivity of community residents during the MERS outbreak correlated with gender, age, occupation, and health behaviors. When there is an outbreak in the community, there is need to maintain a certain level of sensitivity while reducing excessive stress, as well as promote the practice of preventive behaviors among local residents. In particular, target groups need to be notified and policies need to be established with a consideration of the socio-demographic characteristics of the community.",2016 Nov 16,"['Lee, Soon Young', 'Yang, Hee Jeong', 'Kim, Gawon', 'Cheong, Hae-Kwan', 'Choi, Bo Youl']",Epidemiol Health,,,False
7969e6c3564904ffb7928747d52f3edcc7f97fff,PMC,Polymerase cross-linking spiral reaction (PCLSR) for detection of African swine fever virus (ASFV) in pigs and wild boars,http://dx.doi.org/10.1038/srep42903,PMC5309890,28198455,CC BY,"The study reports the development of a polymerase cross-linking spiral reaction (PCLSR) for the detection of African swine fever virus (ASFV) DNA in blood collected from infected pigs and wild boars. The method uses 3 specifically designed primers. Two outer-spiral primers comprising of 3′ sequences complementary to ASFV p72 gene sequence and 5′end sequences complementary to exogenous gene of black widow alpha-latrotoxin as well as additional ASFV specific cross-linking primer. The method is specific exclusively to ASFV DNA without cross-reactions with cDNA of classical swine fever virus (CSFV), porcine reproductive respiratory syndrome (PRRSV) or porcine epidemic diarrhea virus (PEDV). The sensitivity of this technique reached 7.2 × 10(2) copies per μl(−1) of plasmid containing p72 gene. The PCLSR was conducted at 65 °C creating cross-linked complex structures. The results of PCLSR were visualized using SYBR Green I dye, gel electrophoresis while the reaction progress was traced using real-time PCR system that resulted in registration of fluorescent curves and melting peaks at 85.3 °C. The developed PCLSR was examined using blood or tissue samples collected from selected 17 ASF cases from infected wild boars and 3 outbreaks in pigs. Further tests have been also conducted using 55 tissue samples from 23 outbreaks and 22 cases. These results showed that PCLSR might be further used for preliminary and cost-effective detection and surveillance of ASFV.",2017 Feb 15,"['Woźniakowski, Grzegorz', 'Frączyk, Magdalena', 'Kowalczyk, Andrzej', 'Pomorska-Mól, Małgorzata', 'Niemczuk, Krzysztof', 'Pejsak, Zygmunt']",Sci Rep,,,True
b65730c8b239180dd62a079fd2a40f2325a86a78,PMC,"IRAV (FLJ11286), an Interferon-Stimulated Gene with Antiviral Activity against Dengue Virus, Interacts with MOV10",http://dx.doi.org/10.1128/JVI.01606-16,PMC5309953,27974568,CC BY,"Dengue virus (DENV) is a member of the genus Flavivirus and can cause severe febrile illness. Here, we show that FLJ11286, which we refer to as IRAV, is induced by DENV in an interferon-dependent manner, displays antiviral activity against DENV, and localizes to the DENV replication complex. IRAV is an RNA binding protein and localizes to cytoplasmic processing bodies (P bodies) in uninfected cells, where it interacts with the MOV10 RISC complex RNA helicase, suggesting a role for IRAV in the processing of viral RNA. After DENV infection, IRAV, along with MOV10 and Xrn1, localizes to the DENV replication complex and associates with DENV proteins. Depletion of IRAV or MOV10 results in an increase in viral RNA. These data serve to characterize an interferon-stimulated gene with antiviral activity against DENV, as well as to propose a mechanism of activity involving the processing of viral RNA. IMPORTANCE Dengue virus, a member of the family Flaviviridae, can result in a life-threatening illness and has a significant impact on global health. Dengue virus has been shown to be particularly sensitive to the effects of type I interferon; however, little is known about the mechanisms by which interferon-stimulated genes function to inhibit viral replication. A better understanding of the interferon-mediated antiviral response to dengue virus may aid in the development of novel therapeutics. Here, we examine the influence of the interferon-stimulated gene IRAV (FLJ11286) on dengue virus replication. We show that IRAV associates with P bodies in uninfected cells and with the dengue virus replication complex after infection. IRAV also interacts with MOV10, depletion of which is associated with increased viral replication. Our results provide insight into a newly identified antiviral gene, as well as broadening our understanding of the innate immune response to dengue virus infection.",2017 Feb 14,"['Balinsky, Corey A.', 'Schmeisser, Hana', 'Wells, Alexandra I.', 'Ganesan, Sundar', 'Jin, Tengchuan', 'Singh, Kavita', 'Zoon, Kathryn C.']",J Virol,,,True
b39081e0e21045c31022ff4f1d97fbb582d9be8d,PMC,"IRAV (FLJ11286), an Interferon-Stimulated Gene with Antiviral Activity against Dengue Virus, Interacts with MOV10",http://dx.doi.org/10.1128/JVI.01606-16,PMC5309953,27974568,CC BY,"Dengue virus (DENV) is a member of the genus Flavivirus and can cause severe febrile illness. Here, we show that FLJ11286, which we refer to as IRAV, is induced by DENV in an interferon-dependent manner, displays antiviral activity against DENV, and localizes to the DENV replication complex. IRAV is an RNA binding protein and localizes to cytoplasmic processing bodies (P bodies) in uninfected cells, where it interacts with the MOV10 RISC complex RNA helicase, suggesting a role for IRAV in the processing of viral RNA. After DENV infection, IRAV, along with MOV10 and Xrn1, localizes to the DENV replication complex and associates with DENV proteins. Depletion of IRAV or MOV10 results in an increase in viral RNA. These data serve to characterize an interferon-stimulated gene with antiviral activity against DENV, as well as to propose a mechanism of activity involving the processing of viral RNA. IMPORTANCE Dengue virus, a member of the family Flaviviridae, can result in a life-threatening illness and has a significant impact on global health. Dengue virus has been shown to be particularly sensitive to the effects of type I interferon; however, little is known about the mechanisms by which interferon-stimulated genes function to inhibit viral replication. A better understanding of the interferon-mediated antiviral response to dengue virus may aid in the development of novel therapeutics. Here, we examine the influence of the interferon-stimulated gene IRAV (FLJ11286) on dengue virus replication. We show that IRAV associates with P bodies in uninfected cells and with the dengue virus replication complex after infection. IRAV also interacts with MOV10, depletion of which is associated with increased viral replication. Our results provide insight into a newly identified antiviral gene, as well as broadening our understanding of the innate immune response to dengue virus infection.",2017 Feb 14,"['Balinsky, Corey A.', 'Schmeisser, Hana', 'Wells, Alexandra I.', 'Ganesan, Sundar', 'Jin, Tengchuan', 'Singh, Kavita', 'Zoon, Kathryn C.']",J Virol,,,False
9d8670d2d8e18f181af7f6fc61db4424026f384e,PMC,Early immune responses and development of pathogenesis of avian infectious bronchitis viruses with different virulence profiles,http://dx.doi.org/10.1371/journal.pone.0172275,PMC5310907,28199419,CC BY,"Avian infectious bronchitis virus (IBV) primarily replicates in epithelial cells of the upper respiratory tract of chickens, inducing both morphological and immune modulatory changes. However, the association between the local immune responses induced by IBV and the mechanisms of pathogenesis has not yet been completely elucidated. This study compared the expression profile of genes related to immune responses in tracheal samples after challenge with two Brazilian field isolates (A and B) of IBV from the same genotype, associating these responses with viral replication and with pathological changes in trachea and kidney. We detected a suppressive effect on the early activation of TLR7 pathway, followed by lower expression levels of inflammatory related genes induced by challenge with the IBV B isolate when compared to the challenge with to the IBV A isolate. Cell-mediated immune (CMI) related genes presented also lower levels of expression in tracheal samples from birds challenged with B isolate at 1dpi. Increased viral load and a higher percentage of birds with relevant lesions were observed in both tracheal and renal samples from chickens exposed to challenge with IBV B isolate. This differential pattern of early immune responses developed after challenge with IBV B isolate, related to the downregulation of TLR7, leading to insufficient pro-inflammatory response and lower CMI responses, seem to have an association with a most severe renal lesion and an enhanced capability of replication of this isolate in chicken.",2017 Feb 15,"['Okino, Cintia Hiromi', 'Mores, Marcos Antônio Zanella', 'Trevisol, Iara Maria', 'Coldebella, Arlei', 'Montassier, Hélio José', 'Brentano, Liana']",PLoS One,,,True
f76f29653d5c53667e4a9615ca50f8b94c753d36,PMC,Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication,http://dx.doi.org/10.1371/journal.ppat.1006195,PMC5310923,28158275,CC BY,"Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis–within the replicase complex—suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses.",2017 Feb 3,"['Kindler, Eveline', 'Gil-Cruz, Cristina', 'Spanier, Julia', 'Li, Yize', 'Wilhelm, Jochen', 'Rabouw, Huib H.', 'Züst, Roland', 'Hwang, Mihyun', 'V’kovski, Philip', 'Stalder, Hanspeter', 'Marti, Sabrina', 'Habjan, Matthias', 'Cervantes-Barragan, Luisa', 'Elliot, Ruth', 'Karl, Nadja', 'Gaughan, Christina', 'van Kuppeveld, Frank J. M.', 'Silverman, Robert H.', 'Keller, Markus', 'Ludewig, Burkhard', 'Bergmann, Cornelia C.', 'Ziebuhr, John', 'Weiss, Susan R.', 'Kalinke, Ulrich', 'Thiel, Volker']",PLoS Pathog,,,True
595bd63b2b99cb95b0726a0627daa199f5ba0f00,PMC,Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication,http://dx.doi.org/10.1371/journal.ppat.1006195,PMC5310923,28158275,CC BY,"Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis–within the replicase complex—suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses.",2017 Feb 3,"['Kindler, Eveline', 'Gil-Cruz, Cristina', 'Spanier, Julia', 'Li, Yize', 'Wilhelm, Jochen', 'Rabouw, Huib H.', 'Züst, Roland', 'Hwang, Mihyun', 'V’kovski, Philip', 'Stalder, Hanspeter', 'Marti, Sabrina', 'Habjan, Matthias', 'Cervantes-Barragan, Luisa', 'Elliot, Ruth', 'Karl, Nadja', 'Gaughan, Christina', 'van Kuppeveld, Frank J. M.', 'Silverman, Robert H.', 'Keller, Markus', 'Ludewig, Burkhard', 'Bergmann, Cornelia C.', 'Ziebuhr, John', 'Weiss, Susan R.', 'Kalinke, Ulrich', 'Thiel, Volker']",PLoS Pathog,,,False
466f18a2d132e1ccee27235fd5f16b45b1f8ba93,PMC,Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication,http://dx.doi.org/10.1371/journal.ppat.1006195,PMC5310923,28158275,CC BY,"Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis–within the replicase complex—suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses.",2017 Feb 3,"['Kindler, Eveline', 'Gil-Cruz, Cristina', 'Spanier, Julia', 'Li, Yize', 'Wilhelm, Jochen', 'Rabouw, Huib H.', 'Züst, Roland', 'Hwang, Mihyun', 'V’kovski, Philip', 'Stalder, Hanspeter', 'Marti, Sabrina', 'Habjan, Matthias', 'Cervantes-Barragan, Luisa', 'Elliot, Ruth', 'Karl, Nadja', 'Gaughan, Christina', 'van Kuppeveld, Frank J. M.', 'Silverman, Robert H.', 'Keller, Markus', 'Ludewig, Burkhard', 'Bergmann, Cornelia C.', 'Ziebuhr, John', 'Weiss, Susan R.', 'Kalinke, Ulrich', 'Thiel, Volker']",PLoS Pathog,,,False
b8567708fbc399167a11ae6ac3d9482f68bd7b24,PMC,A Blueprint to Evaluate One Health,http://dx.doi.org/10.3389/fpubh.2017.00020,PMC5311072,28261580,CC BY,"One Health (OH) positions health professionals as agents for change and provides a platform to manage determinants of health that are often not comprehensively captured in medicine or public health alone. However, due to the organization of societies and disciplines, and the sectoral allocation of resources, the development of transdisciplinary approaches requires effort and perseverance. Therefore, there is a need to provide evidence on the added value of OH for governments, researchers, funding bodies, and stakeholders. This paper outlines a conceptual framework of what OH approaches can encompass and the added values they can provide. The framework was developed during a workshop conducted by the “Network for Evaluation of One Health,” an Action funded by the European Cooperation in Science and Technology. By systematically describing the various aspects of OH, we provide the basis for measuring and monitoring the integration of disciplines, sectors, and stakeholders in health initiatives. The framework identifies the social, economic, and environmental drivers leading to integrated approaches to health and illustrates how these evoke characteristic OH operations, i.e., thinking, planning, and working, and require supporting infrastructures to allow learning, sharing, and systemic organization. It also describes the OH outcomes (i.e., sustainability, health and welfare, interspecies equity and stewardship, effectiveness, and efficiency), which are not possible to obtain through sectoral approaches alone, and their alignment with aspects of sustainable development based on society, environment, and economy.",2017 Feb 16,"['Rüegg, Simon R.', 'McMahon, Barry J.', 'Häsler, Barbara', 'Esposito, Roberto', 'Nielsen, Liza Rosenbaum', 'Ifejika Speranza, Chinwe', 'Ehlinger, Timothy', 'Peyre, Marisa', 'Aragrande, Maurizio', 'Zinsstag, Jakob', 'Davies, Philip', 'Mihalca, Andrei Daniel', 'Buttigieg, Sandra C.', 'Rushton, Jonathan', 'Carmo, Luís P.', 'De Meneghi, Daniele', 'Canali, Massimo', 'Filippitzi, Maria E.', 'Goutard, Flavie Luce', 'Ilieski, Vlatko', 'Milićević, Dragan', 'O’Shea, Helen', 'Radeski, Miroslav', 'Kock, Richard', 'Staines, Anthony', 'Lindberg, Ann']",Front Public Health,,,True
87c3f3ef6a719daba2049b5d7981486a6f1259c8,PMC,An empirical analysis of the Ebola outbreak in West Africa,http://dx.doi.org/10.1038/srep42594,PMC5311974,28205617,CC BY,"The data for the Ebola outbreak that occurred in 2014–2016 in three countries of West Africa are analysed within a common framework. The analysis is made using the results of an agent based Susceptible-Infected-Removed (SIR) model on a Euclidean network, where nodes at a distance l are connected with probability P(l) ∝ l(−δ), δ determining the range of the interaction, in addition to nearest neighbors. The cumulative (total) density of infected population here has the form [Image: see text], where the parameters depend on δ and the infection probability q. This form is seen to fit well with the data. Using the best fitting parameters, the time at which the peak is reached is estimated and is shown to be consistent with the data. We also show that in the Euclidean model, one can choose δ and q values which reproduce the data for the three countries qualitatively. These choices are correlated with population density, control schemes and other factors. Comparing the real data and the results from the model one can also estimate the size of the actual population susceptible to the disease. Rescaling the real data a reasonably good quantitative agreement with the simulation results is obtained.",2017 Feb 16,"['Khaleque, Abdul', 'Sen, Parongama']",Sci Rep,,,True
2e3d6708bedf2af3d3b900329871c910308b0b7a,PMC,Identification of Human Junctional Adhesion Molecule 1 as a Functional Receptor for the Hom-1 Calicivirus on Human Cells,http://dx.doi.org/10.1128/mBio.00031-17,PMC5312078,28196955,CC BY,"The Hom-1 vesivirus was reported in 1998 following the inadvertent transmission of the animal calicivirus San Miguel sea lion virus to a human host in a laboratory. We characterized the Hom-1 strain and investigated the mechanism by which human cells could be infected. An expression library of 3,559 human plasma membrane proteins was screened for reactivity with Hom-1 virus-like particles, and a single interacting protein, human junctional adhesion molecule 1 (hJAM1), was identified. Transient expression of hJAM1 conferred susceptibility to Hom-1 infection on nonpermissive Chinese hamster ovary (CHO) cells. Virus infection was markedly inhibited when CHO cells stably expressing hJAM were pretreated with anti-hJAM1 monoclonal antibodies. Cell lines of human origin were tested for growth of Hom-1, and efficient replication was observed in HepG2, HuH7, and SK-CO15 cells. The three cell lines (of hepatic or intestinal origin) were confirmed to express hJAM1 on their surface, and clustered regularly interspaced short palindromic repeats/Cas9-mediated knockout of the hJAM1 gene in each line abolished Hom-1 propagation. Taken together, our data indicate that entry of the Hom-1 vesivirus into these permissive human cell lines is mediated by the plasma membrane protein hJAM1 as a functional receptor.",2017 Feb 14,"['Sosnovtsev, Stanislav V.', 'Sandoval-Jaime, Carlos', 'Parra, Gabriel I.', 'Tin, Christine M.', 'Jones, Ronald W.', 'Soden, Jo', 'Barnes, Donna', 'Freeth, Jim', 'Smith, Alvin W.', 'Green, Kim Y.']",mBio,,,True
c273806c4c0c22f467f8f466472d1de67a175ae9,PMC,Identification of Human Junctional Adhesion Molecule 1 as a Functional Receptor for the Hom-1 Calicivirus on Human Cells,http://dx.doi.org/10.1128/mBio.00031-17,PMC5312078,28196955,CC BY,"The Hom-1 vesivirus was reported in 1998 following the inadvertent transmission of the animal calicivirus San Miguel sea lion virus to a human host in a laboratory. We characterized the Hom-1 strain and investigated the mechanism by which human cells could be infected. An expression library of 3,559 human plasma membrane proteins was screened for reactivity with Hom-1 virus-like particles, and a single interacting protein, human junctional adhesion molecule 1 (hJAM1), was identified. Transient expression of hJAM1 conferred susceptibility to Hom-1 infection on nonpermissive Chinese hamster ovary (CHO) cells. Virus infection was markedly inhibited when CHO cells stably expressing hJAM were pretreated with anti-hJAM1 monoclonal antibodies. Cell lines of human origin were tested for growth of Hom-1, and efficient replication was observed in HepG2, HuH7, and SK-CO15 cells. The three cell lines (of hepatic or intestinal origin) were confirmed to express hJAM1 on their surface, and clustered regularly interspaced short palindromic repeats/Cas9-mediated knockout of the hJAM1 gene in each line abolished Hom-1 propagation. Taken together, our data indicate that entry of the Hom-1 vesivirus into these permissive human cell lines is mediated by the plasma membrane protein hJAM1 as a functional receptor.",2017 Feb 14,"['Sosnovtsev, Stanislav V.', 'Sandoval-Jaime, Carlos', 'Parra, Gabriel I.', 'Tin, Christine M.', 'Jones, Ronald W.', 'Soden, Jo', 'Barnes, Donna', 'Freeth, Jim', 'Smith, Alvin W.', 'Green, Kim Y.']",mBio,,,False
1738091122ca5ec9b277875d05e0b3f1bbb758dc,PMC,Identification of Human Junctional Adhesion Molecule 1 as a Functional Receptor for the Hom-1 Calicivirus on Human Cells,http://dx.doi.org/10.1128/mBio.00031-17,PMC5312078,28196955,CC BY,"The Hom-1 vesivirus was reported in 1998 following the inadvertent transmission of the animal calicivirus San Miguel sea lion virus to a human host in a laboratory. We characterized the Hom-1 strain and investigated the mechanism by which human cells could be infected. An expression library of 3,559 human plasma membrane proteins was screened for reactivity with Hom-1 virus-like particles, and a single interacting protein, human junctional adhesion molecule 1 (hJAM1), was identified. Transient expression of hJAM1 conferred susceptibility to Hom-1 infection on nonpermissive Chinese hamster ovary (CHO) cells. Virus infection was markedly inhibited when CHO cells stably expressing hJAM were pretreated with anti-hJAM1 monoclonal antibodies. Cell lines of human origin were tested for growth of Hom-1, and efficient replication was observed in HepG2, HuH7, and SK-CO15 cells. The three cell lines (of hepatic or intestinal origin) were confirmed to express hJAM1 on their surface, and clustered regularly interspaced short palindromic repeats/Cas9-mediated knockout of the hJAM1 gene in each line abolished Hom-1 propagation. Taken together, our data indicate that entry of the Hom-1 vesivirus into these permissive human cell lines is mediated by the plasma membrane protein hJAM1 as a functional receptor.",2017 Feb 14,"['Sosnovtsev, Stanislav V.', 'Sandoval-Jaime, Carlos', 'Parra, Gabriel I.', 'Tin, Christine M.', 'Jones, Ronald W.', 'Soden, Jo', 'Barnes, Donna', 'Freeth, Jim', 'Smith, Alvin W.', 'Green, Kim Y.']",mBio,,,False
fd1b78b3eba6d55adc09671bb6942c90b3ad6fe5,PMC,Identification of Human Junctional Adhesion Molecule 1 as a Functional Receptor for the Hom-1 Calicivirus on Human Cells,http://dx.doi.org/10.1128/mBio.00031-17,PMC5312078,28196955,CC BY,"The Hom-1 vesivirus was reported in 1998 following the inadvertent transmission of the animal calicivirus San Miguel sea lion virus to a human host in a laboratory. We characterized the Hom-1 strain and investigated the mechanism by which human cells could be infected. An expression library of 3,559 human plasma membrane proteins was screened for reactivity with Hom-1 virus-like particles, and a single interacting protein, human junctional adhesion molecule 1 (hJAM1), was identified. Transient expression of hJAM1 conferred susceptibility to Hom-1 infection on nonpermissive Chinese hamster ovary (CHO) cells. Virus infection was markedly inhibited when CHO cells stably expressing hJAM were pretreated with anti-hJAM1 monoclonal antibodies. Cell lines of human origin were tested for growth of Hom-1, and efficient replication was observed in HepG2, HuH7, and SK-CO15 cells. The three cell lines (of hepatic or intestinal origin) were confirmed to express hJAM1 on their surface, and clustered regularly interspaced short palindromic repeats/Cas9-mediated knockout of the hJAM1 gene in each line abolished Hom-1 propagation. Taken together, our data indicate that entry of the Hom-1 vesivirus into these permissive human cell lines is mediated by the plasma membrane protein hJAM1 as a functional receptor.",2017 Feb 14,"['Sosnovtsev, Stanislav V.', 'Sandoval-Jaime, Carlos', 'Parra, Gabriel I.', 'Tin, Christine M.', 'Jones, Ronald W.', 'Soden, Jo', 'Barnes, Donna', 'Freeth, Jim', 'Smith, Alvin W.', 'Green, Kim Y.']",mBio,,,False
c0de9d0fcd1d7f778c11f42fd399f6c0cc5e7a4b,PMC,An indirect enzyme-linked immunosorbent assay for the identification of antibodies to Senecavirus A in swine,http://dx.doi.org/10.1186/s12917-017-0967-x,PMC5312445,28202026,CC BY,"BACKGROUND: Senecavirus A (SVA), a member of the family Picornaviridae, genus Senecavirus, is a recently identified single-stranded RNA virus closely related to members of the Cardiovirus genus. SVA was originally identified as a cell culture contaminant and was not associated with disease until 2007 when it was first observed in pigs with Idiopathic Vesicular Disease (IVD). Vesicular disease is sporadically observed in swine, is not debilitating, but is significant due to its resemblance to foreign animal diseases, such as foot-and-mouth disease (FMD), whose presence would be economically devastating to the United States. IVD disrupts swine production until foreign animal diseases can be ruled out. Identification and characterization of SVA as a cause of IVD will help to quickly rule out infection by foreign animal diseases. METHODS: We have developed and characterized an indirect ELISA assay to specifically identify serum antibodies to SVA. Viral protein 1, 2 and 3 (VP1, VP2, VP3) were expressed, isolated, and purified from E. coli and used to coat plates for an indirect ELISA. Sera from pigs with and without IVD symptoms as well as a time course following animals from an infected farm, were analyzed to determine the antibody responses to VP1, VP2, and VP3. RESULTS: Antibody responses to VP2 were higher than VP1 and VP3 and showed high affinity binding on an avidity ELISA. ROC analysis of the SVA VP2 ELISA showed a sensitivity of 94.2% and a specificity of 89.7%. Compared to IFA, the quantitative ELISA showed an 89% agreement in negative samples and positive samples from 4–60 days after appearance of clinical signs. Immune sera positive for FMDV, encephalomyocarditis virus, and porcine epidemic diarrhea virus antibodies did not cross-react. CONCLUSIONS: A simple ELISA based on detection of antibodies to SVA VP2 will help to differentially diagnose IVD due to SVA and rule out the presence of economically devastating foreign animal diseases.",2017 Feb 15,"['Dvorak, Cheryl M. T.', 'Akkutay-Yoldar, Zeynep', 'Stone, Suzanne R.', 'Tousignant, Steven J.P.', 'Vannucci, Fabio A.', 'Murtaugh, Michael P.']",BMC Vet Res,,,True
f3bc1d07fd0e855faa2e2eb98d9b97852eb88c03,PMC,Justifications for Non-Consensual Medical Intervention: From Infectious Disease Control to Criminal Rehabilitation,http://dx.doi.org/10.1080/0731129X.2016.1247519,PMC5312796,28260832,CC BY,A central tenet of medical ethics holds that it is permissible to perform a medical intervention on a competent individual only if that individual has given informed consent to the intervention. Yet it occasionally seems morally permissible to carry out non-consensual medical interventions on competent individuals for the purpose of infectious disease control (IDC). We describe two different moral frameworks that have been invoked in support of non-consensual IDC interventions and identify five desiderata that might be used to guide assessments of the moral permissibility of such interventions on either kind of fundamental justification. We then consider what these desiderata imply for the justifiability of carrying out non-consensual medical interventions that are designed to facilitate rehabilitation amongst serious criminal offenders. We argue that these desiderata suggest that a plausible case can be made in favor of such interventions.,2016 Sep 1,"['Pugh, Jonathan', 'Douglas, Thomas']",Crim Justice Ethics,,,True
534bc15ce844653ae863844b86d4ace2b98d42a3,PMC,Diversity of Cryptosporidium species occurring in sheep and goat breeds reared in Poland,http://dx.doi.org/10.1007/s00436-016-5360-3,PMC5313596,28058536,CC BY,"The aim of this study was molecular identification of Cryptosporidium species and assessment of their prevalence in different breeds of sheep and goat reared in Poland. In addition, the relationship between animal age, breed type, and the frequency of Cryptosporidium infections was determined. Fecal samples from 234 lambs and 105 goat kids aged up to 9 weeks, representing 24 breeds and their cross-breeds were collected from 71 small ruminant farms across Poland. The identification of Cryptosporidium species was performed at the 18 SSU ribosomal RNA (rRNA) and COWP loci followed by subtyping of C. parvum and C. hominis strains at GP60 gene locus. The presence of Cryptosporidium DNA at the 18 SSU rRNA locus was detected in 45/234 (19.2%) lamb feces samples and in 39/105 (37.1%) taken from goats. The following Cryptosporidium species: C. xiaoi, C. bovis, C. ubiquitum, C. parvum, and C. hominis were detected in small ruminants. Infections caused by C. xiaoi were predominant without favoring any tested animal species. Subsequent GP60 subtyping revealed the presence of C. parvum IIaA17G1R1 subtype in sheep and IIdA23G1 subtype in goats. IIdA23G1 subtype was detected in a goat host for the first time. There were no significant differences found in frequency of infections between the age groups (<3 and 3–9 weeks) of lambs (P = 0.14, α > 0.05) or goat kids (P = 0.06, α > 0.05). In addition, there was no correlation observed between the frequency in occurrence of particular parasite species and breed type in relation to native sheep breeds (F = 0.11; P = 0.990 > 0.05). In the case of goats, more breed-related differences in parasite occurrence were found. The results of this study improve our knowledge on the breed-related occurrence of Cryptosporidium infections in the population of small ruminants reared in Poland.",2017 Jan 5,"['Kaupke, Agnieszka', 'Michalski, Mirosław M.', 'Rzeżutka, Artur']",Parasitol Res,,,True
dd4c8ed4c8651c73d3d13a61cd7d14c9eb1fa745,PMC,Improving Biosurveillance Systems to Enable Situational Awareness During Public Health Emergencies,http://dx.doi.org/10.1089/hs.2016.0097,PMC5314963,28092456,CC BY,,2017 Feb 1,"Nuzzo, Jennifer B.",Health Secur,,,True
d66abf26034eafcdafdbcdac0b082a337ac2ffee,PMC,International Engagement Is Critical to Fighting Epidemics,http://dx.doi.org/10.1089/hs.2016.0098,PMC5314974,28092453,CC BY,,2017 Feb 1,"['Nuzzo, Jennifer B.', 'Shearer, Matthew P.']",Health Secur,,,True
fb784725f25eb2d627a8b28eb118efaa701a95d1,PMC,Strengthening the US Medical Countermeasure Enterprise for Biological Threats,http://dx.doi.org/10.1089/hs.2016.0119,PMC5314975,28092470,CC BY,,2017 Feb 1,"['Ravi, Sanjana', 'Adalja, Amesh A.']",Health Secur,,,False
1174cadd31854c1128f0bbf2a61d31b2b72f61c3,PMC,Complementary and alternative medicine for the treatment of bronchiolitis in infants: A systematic review,http://dx.doi.org/10.1371/journal.pone.0172289,PMC5315308,28212381,CC BY,"BACKGROUND: Bronchiolitis is a common cause of hospitalization among infants. The limited effectiveness of conventional medication has prompted the use of complementary and alternative medicine (CAM) as alternative or adjunctive therapy for the management of bronchiolitis. AIMS: To determine the effectiveness and safety of CAM for the treatment of bronchiolitis in infants aged less than 2 years. METHODS: A systematic electronic search was performed in Medline, Embase, CINAHL, AMED, and Cochrane Central Register of Controlled Trials (CENTRAL) from their respective inception to June 30, 2016 for studies evaluating CAM as an intervention to treat bronchiolitis in infants (1 month to 2 years of age). The CAM could be any form of treatment defined by the National Center for Complementary and Integrative Health (NCCIH) and was utilized either as a single agent or adjunctive therapy. The predefined primary outcome was length of hospital stay. Secondary outcomes were time to resolution of bronchiolitis symptoms, adverse events, and all other clinical outcomes reported by the included studies. RESULTS: The review identified 11 studies (8 randomized controlled trials and 3 cohort studies) examining four herbal preparations and four supplements used either as adjunctive or alternative therapy for bronchiolitis in 904 infants. Most studies were of moderate quality. Among six studies reporting on length of stay, a significant benefit was found for Chinese herbal medicine compared to ribavirin in one cohort study (n = 66) and vitamin D compared to placebo in one randomized controlled trial (n = 89). Studies of Chinese herbal medicine (4 studies, n = 365), vitamin D (1 study, n = 89), N-acetylcysteine (1 study, n = 100), and magnesium (2 studies, n = 176) showed some benefits with respect to clinical severity scores, oxygen saturation, and other symptoms, although data were sparse for any single intervention and the outcomes assessed and reported varied across studies. Only five studies reported on adverse events; no serious adverse events were reported. CONCLUSIONS: Among 11 studies examining the effect of CAM on inpatients with bronchiolitis, six reported on the review’s primary outcome of length of hospital stay. In general, findings did not show a significant benefit associated with the primary outcome. Preliminary evidence indicated that Chinese herbal medicine mixtures, vitamin D, N-acetylcysteine, and magnesium might be useful in managing the symptoms of bronchiolitis. However, the evidence was not sufficient or rigorous enough to formulate recommendations for the use of any CAM. Among studies that reported adverse events, no serious harms were noted.",2017 Feb 17,"['Kua, Kok Pim', 'Lee, Shaun Wen Huey']",PLoS One,,,True
6ed0c79fde1a2d37093e6a97ee3ffb2d8c4410eb,PMC,Prioritizing zoonotic diseases in Ethiopia using a one health approach,http://dx.doi.org/10.1016/j.onehlt.2016.09.001,PMC5315415,28220151,CC BY,"BACKGROUND: Ethiopia has the second largest human population in Africa and the largest livestock population on the continent. About 80% of Ethiopians are dependent on agriculture and have direct contact with livestock or other domestic animals. As a result, the country is vulnerable to the spread of zoonotic diseases. As the first step of the country's engagement in the Global Health Security Agenda, a zoonotic disease prioritization workshop was held to identify significant zoonotic diseases of mutual concern for animal and human health agencies. METHODS: A semi-quantitative tool developed by the US CDC was used for prioritization of zoonotic diseases. Workshop participants representing human, animal, and environmental health ministries were selected as core decision-making participants. Over 300 articles describing the zoonotic diseases considered at the workshop were reviewed for disease specific information on prevalence, morbidity, mortality, and DALYs for Ethiopia or the East Africa region. Committee members individually ranked the importance of each criterion to generate a final group weight for each criterion. RESULTS: Forty-three zoonotic diseases were evaluated. Criteria selected in order of importance were: 1)severity of disease in humans, 2)proportion of human disease attributed to animal exposure, 3)burden of animal disease, 4)availability of interventions, and 5)existing inter-sectoral collaboration. Based on the results from the decision tree analysis and subsequent discussion, participants identified the following five priority zoonotic diseases: rabies, anthrax, brucellosis, leptospirosis, and echinococcosis. DISCUSSION: Multi-sectoral collaborations strengthen disease surveillance system development in humans and animals, enhance laboratory capacity, and support implementation of prevention and control strategies. To facilitate this, the creation of a One Health-focused Zoonotic Disease Unit is recommended. Enhancement of public health and veterinary laboratories, joint outbreak and surveillance activities, and intersectoral linkages created to tackle the prioritized zoonotic diseases will undoubtedly prepare the country to effectively address newly emerging zoonotic diseases.",2016 Sep 15,"['Pieracci, Emily G.', 'Hall, Aron J.', 'Gharpure, Radhika', 'Haile, Abraham', 'Walelign, Elias', 'Deressa, Asefa', 'Bahiru, Getahun', 'Kibebe, Meron', 'Walke, Henry', 'Ermias Belay']",One Health,,,True
644979755526ea0ca2ce4990c87f0dd9342aaf89,PMC,Development of in vitro and in vivo rabies virus neutralization assays based on a high-titer pseudovirus system,http://dx.doi.org/10.1038/srep42769,PMC5316940,28218278,CC BY,"Pseudoviruses are useful virological tools because of their safety and versatility; however the low titer of these viruses substantially limits their wider applications. We developed a highly efficient pseudovirus production system capable of yielding 100 times more rabies pseudovirus than the traditional method. Employing the high-titer pseudoviruses, we have developed robust in vitro and in vivo neutralization assays for the evaluation of rabies vaccine, which traditionally relies on live-virus based assays. Compared with current rapid fluorescent focus inhibition test (RFFIT), our in vitro pseudovirus-based neutralization assay (PBNA) is much less labor-intensive while demonstrating better reproducibility. Moreover, the in vivo PBNA assay was also found to be superior to the live virus based assay. Following intravenous administration, the pseudovirus effectively infected the mice, with dynamic viral distributions being sequentially observed in spleen, liver and brain. Furthermore, data from in vivo PBNA showed great agreement with those generated from the live virus model but with the experimental time significantly reduced from 2 weeks to 3 days. Taken together, the effective pseudovirus production system facilitated the development of novel PBNA assays which could replace live virus-based traditional assays due to its safety, rapidity, reproducibility and high throughput capacity.",2017 Feb 20,"['Nie, Jianhui', 'Wu, Xiaohong', 'Ma, Jian', 'Cao, Shouchun', 'Huang, Weijin', 'Liu, Qiang', 'Li, Xuguang', 'Li, Yuhua', 'Wang, Youchun']",Sci Rep,,,True
c29e836db0541b34ffaf6a75c8b7079fd98220d8,PMC,Detection of viral respiratory pathogens in mild and severe acute respiratory infections in Singapore,http://dx.doi.org/10.1038/srep42963,PMC5317157,28218288,CC BY,"To investigate the performance of laboratory methods and clinical case definitions in detecting the viral pathogens for acute respiratory infections (ARIs) from a prospective community cohort and hospital inpatients, nasopharyngeal swabs from cohort members reporting ARIs (community-ARI) and inpatients admitted with ARIs (inpatient-ARI) were tested by Singleplex Real Time-Polymerase Chain Reaction (SRT-PCR), multiplex RT-PCR (MRT-PCR) and pathogen-chip system (PathChip) between April 2012 and December 2013. Community-ARI and inpatient-ARI was also combined with mild and severe cases of influenza from a historical prospective study as mild-ARI and severe-ARI respectively to evaluate the performance of clinical case definitions. We analysed 130 community-ARI and 140 inpatient-ARI episodes (5 inpatient-ARI excluded because multiple pathogens were detected), involving 138 and 207 samples respectively. Detection by PCR declined with days post-onset for influenza virus; decrease was faster for community-ARI than for inpatient-ARI. No such patterns were observed for non-influenza respiratory virus infections. PathChip added substantially to viruses detected for community-ARI only. Clinical case definitions discriminated influenza from other mild-ARI but performed poorly for severe-ARI and for older participants. Rational strategies for diagnosis and surveillance of influenza and other respiratory virus must acknowledge the differences between ARIs presenting in community and hospital settings.",2017 Feb 20,"['Jiang, Lili', 'Lee, Vernon Jian Ming', 'Cui, Lin', 'Lin, Raymond', 'Tan, Chyi Lin', 'Tan, Linda Wei Lin', 'Lim, Wei-yen', 'Leo, Yee-Sin', 'Low, Louie', 'Hibberd, Martin', 'Chen, Mark I-Cheng']",Sci Rep,,,True
7cbf56502db60d62b5255c560670ef9ced099c30,PMC,Human enterovirus 71 protein interaction network prompts antiviral drug repositioning,http://dx.doi.org/10.1038/srep43143,PMC5318855,28220872,CC BY,"As a predominant cause of human hand, foot, and mouth disease, enterovirus 71 (EV71) infection may lead to serious diseases and result in severe consequences that threaten public health and cause widespread panic. Although the systematic identification of physical interactions between viral proteins and host proteins provides initial information for the recognition of the cellular mechanism involved in viral infection and the development of new therapies, EV71-host protein interactions have not been explored. Here, we identified interactions between EV71 proteins and host cellular proteins and confirmed the functional relationships of EV71-interacting proteins (EIPs) with virus proliferation and infection by integrating a human protein interaction network and by functional annotation. We found that most EIPs had known interactions with other viruses. We also predicted ATP6V0C as a broad-spectrum essential host factor and validated its essentiality for EV71 infection in vitro. EIPs and their interacting proteins were more likely to be targets of anti-inflammatory and neurological drugs, indicating their potential to serve as host-oriented antiviral targets. Thus, we used a connectivity map to find drugs that inhibited EIP expression. We predicted tanespimycin as a candidate and demonstrated its antiviral efficiency in vitro. These findings provide the first systematic identification of EV71-host protein interactions, an analysis of EIP protein characteristics and a demonstration of their value in developing host-oriented antiviral therapies.",2017 Feb 21,"['Han, Lu', 'Li, Kang', 'Jin, Chaozhi', 'Wang, Jian', 'Li, Qingjun', 'Zhang, Qiling', 'Cheng, Qiyue', 'Yang, Jing', 'Bo, Xiaochen', 'Wang, Shengqi']",Sci Rep,,,True
fd409125a569a4039b4a127b043b6f939433c1f4,PMC,Human enterovirus 71 protein interaction network prompts antiviral drug repositioning,http://dx.doi.org/10.1038/srep43143,PMC5318855,28220872,CC BY,"As a predominant cause of human hand, foot, and mouth disease, enterovirus 71 (EV71) infection may lead to serious diseases and result in severe consequences that threaten public health and cause widespread panic. Although the systematic identification of physical interactions between viral proteins and host proteins provides initial information for the recognition of the cellular mechanism involved in viral infection and the development of new therapies, EV71-host protein interactions have not been explored. Here, we identified interactions between EV71 proteins and host cellular proteins and confirmed the functional relationships of EV71-interacting proteins (EIPs) with virus proliferation and infection by integrating a human protein interaction network and by functional annotation. We found that most EIPs had known interactions with other viruses. We also predicted ATP6V0C as a broad-spectrum essential host factor and validated its essentiality for EV71 infection in vitro. EIPs and their interacting proteins were more likely to be targets of anti-inflammatory and neurological drugs, indicating their potential to serve as host-oriented antiviral targets. Thus, we used a connectivity map to find drugs that inhibited EIP expression. We predicted tanespimycin as a candidate and demonstrated its antiviral efficiency in vitro. These findings provide the first systematic identification of EV71-host protein interactions, an analysis of EIP protein characteristics and a demonstration of their value in developing host-oriented antiviral therapies.",2017 Feb 21,"['Han, Lu', 'Li, Kang', 'Jin, Chaozhi', 'Wang, Jian', 'Li, Qingjun', 'Zhang, Qiling', 'Cheng, Qiyue', 'Yang, Jing', 'Bo, Xiaochen', 'Wang, Shengqi']",Sci Rep,,,False
3ac512d142c583daae040f2dc71312ea804b4f0a,PMC,Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families,http://dx.doi.org/10.1371/journal.ppat.1006215,PMC5319820,28178344,CC BY,"The cross-species transmission of viruses from one host species to another is responsible for the majority of emerging infections. However, it is unclear whether some virus families have a greater propensity to jump host species than others. If related viruses have an evolutionary history of co-divergence with their hosts there should be evidence of topological similarities between the virus and host phylogenetic trees, whereas host jumping generates incongruent tree topologies. By analyzing co-phylogenetic processes in 19 virus families and their eukaryotic hosts we provide a quantitative and comparative estimate of the relative frequency of virus-host co-divergence versus cross-species transmission among virus families. Notably, our analysis reveals that cross-species transmission is a near universal feature of the viruses analyzed here, with virus-host co-divergence occurring less frequently and always on a subset of viruses. Despite the overall high topological incongruence among virus and host phylogenies, the Hepadnaviridae, Polyomaviridae, Poxviridae, Papillomaviridae and Adenoviridae, all of which possess double-stranded DNA genomes, exhibited more frequent co-divergence than the other virus families studied here. At the other extreme, the virus and host trees for all the RNA viruses studied here, particularly the Rhabdoviridae and the Picornaviridae, displayed high levels of topological incongruence, indicative of frequent host switching. Overall, we show that cross-species transmission plays a major role in virus evolution, with all the virus families studied here having the potential to jump host species, and that increased sampling will likely reveal more instances of host jumping.",2017 Feb 8,"['Geoghegan, Jemma L.', 'Duchêne, Sebastián', 'Holmes, Edward C.']",PLoS Pathog,,,True
ebf2755fe646b555ba8aed8b2044e8e764be8307,PMC,Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families,http://dx.doi.org/10.1371/journal.ppat.1006215,PMC5319820,28178344,CC BY,"The cross-species transmission of viruses from one host species to another is responsible for the majority of emerging infections. However, it is unclear whether some virus families have a greater propensity to jump host species than others. If related viruses have an evolutionary history of co-divergence with their hosts there should be evidence of topological similarities between the virus and host phylogenetic trees, whereas host jumping generates incongruent tree topologies. By analyzing co-phylogenetic processes in 19 virus families and their eukaryotic hosts we provide a quantitative and comparative estimate of the relative frequency of virus-host co-divergence versus cross-species transmission among virus families. Notably, our analysis reveals that cross-species transmission is a near universal feature of the viruses analyzed here, with virus-host co-divergence occurring less frequently and always on a subset of viruses. Despite the overall high topological incongruence among virus and host phylogenies, the Hepadnaviridae, Polyomaviridae, Poxviridae, Papillomaviridae and Adenoviridae, all of which possess double-stranded DNA genomes, exhibited more frequent co-divergence than the other virus families studied here. At the other extreme, the virus and host trees for all the RNA viruses studied here, particularly the Rhabdoviridae and the Picornaviridae, displayed high levels of topological incongruence, indicative of frequent host switching. Overall, we show that cross-species transmission plays a major role in virus evolution, with all the virus families studied here having the potential to jump host species, and that increased sampling will likely reveal more instances of host jumping.",2017 Feb 8,"['Geoghegan, Jemma L.', 'Duchêne, Sebastián', 'Holmes, Edward C.']",PLoS Pathog,,,False
2759426af4c8df595f4b5e76b614712fda6da5d3,PMC,K-Pax2: Bayesian identification of cluster-defining amino acid positions in large sequence datasets,http://dx.doi.org/10.1099/mgen.0.000025,PMC5320600,28348810,CC BY,"The recent growth in publicly available sequence data has introduced new opportunities for studying microbial evolution and spread. Because the pace of sequence accumulation tends to exceed the pace of experimental studies of protein function and the roles of individual amino acids, statistical tools to identify meaningful patterns in protein diversity are essential. Large sequence alignments from fast-evolving micro-organisms are particularly challenging to dissect using standard tools from phylogenetics and multivariate statistics because biologically relevant functional signals are easily masked by neutral variation and noise. To meet this need, a novel computational method is introduced that is easily executed in parallel using a cluster environment and can handle thousands of sequences with minimal subjective input from the user. The usefulness of this kind of machine learning is demonstrated by applying it to nearly 5000 haemagglutinin sequences of influenza A/H3N2.Antigenic and 3D structural mapping of the results show that the method can recover the major jumps in antigenic phenotype that occurred between 1968 and 2013 and identify specific amino acids associated with these changes. The method is expected to provide a useful tool to uncover patterns of protein evolution.",2015 Jul 15,"['Pessia, Alberto', 'Grad, Yonatan', 'Cobey, Sarah', 'Puranen, Juha Santeri', 'Corander, Jukka']",Microb Genom,,,True
70748788b2a175a08f02878c528efbd024a45064,PMC,Nitric oxide-generating compound GSNO suppresses porcine circovirus type 2 infection in vitro and in vivo,http://dx.doi.org/10.1186/s12917-017-0976-9,PMC5320642,28222773,CC BY,"BACKGROUND: Nitric oxide (NO), an important signaling molecule with biological functions, has antimicrobial activity against a variety of pathogens including viruses. To our knowledge, little information is available about the regulatory effect of NO on porcine circovirus type 2 (PCV2) infection. This study was conducted to investigate the antiviral activity of NO generated from S-nitrosoglutathione (GSNO), during PCV2 infection of PK-15 cells and BALB/c mice. RESULTS: GSNO released considerable NO in the culture medium of PK-15 cells, and NO was scavenged by its scavenger hemoglobin (Hb) in a dose-dependent manner. NO strongly inhibited PCV2 replication in PK-15 cells, and the antiviral effect was reversed by Hb. An in vivo assay indicated that GSNO treatment reduced the progression of PCV2 infection in mice, evident as reductions in the percentages of PCV2-positive sera and tissue samples and in the viral DNA copies in serum samples. GSNO also improved the growth performance and immune organs (spleens and thymuses) of the PCV2-infected mice to some degree. CONCLUSIONS: Our data demonstrate that the NO-generating compound GSNO suppresses PCV2 infection in PK-15 cells and BALB/c mice, indicating that NO and its donor, GSNO, have potential value as antiviral drugs against PCV2 infection.",2017 Feb 21,"['Liu, Chuanmin', 'Wen, Libin', 'Xiao, Qi', 'He, Kongwang']",BMC Vet Res,,,True
29f305ed687e42fc04b6707fbcc31d95f5588ab7,PMC,A statistical method utilizing information of imported cases to estimate the transmissibility for an influenza pandemic,http://dx.doi.org/10.1186/s12874-017-0300-1,PMC5320693,28222682,CC BY,"BACKGROUND: In a new influenza pandemic, travel data such as arrival times of cases seeded by the originating country can be regarded as a combination of the epidemic size and the mobility networks of infections connecting the originating country with other regions. It can be a complete and timely source for estimating the basic reproduction number (R (0)), a key indicator of disease transmissibility. METHOD: In this study, we developed a likelihood-based method using arrival times of infected cases in different countries to estimate R (0) for influenza pandemics. A simulation was conducted to assess the performance of the proposed method. We further applied the method to the outbreak of the influenza pandemic A/H1N1 in Mexico. RESULTS: In the numerical application, the estimated R (0) was equal to 1.69 with a 95% confidence interval (1.65, 1.73). For the simulation results, the estimations were robust to the decline of travel rate and other parameter assumptions. Nevertheless, the estimates were moderately sensitive to the assumption of infectious duration. Generally, the findings were in line with other relevant studies. CONCLUSIONS: Our approach as well as the estimate is potential to assist officials in planning control and prevention measures. Improved coordination to streamline or even centralize surveillance of imported cases among countries will thus be beneficial to public health.",2017 Feb 21,"['Chong, Ka Chun', 'Zee, Benny Chung Ying', 'Wang, Maggie Haitian']",BMC Med Res Methodol,,,True
2271ecb14bddddc60f33827495cb727858789ba9,PMC,Detection and genome characterization of four novel bat hepadnaviruses and a hepevirus in China,http://dx.doi.org/10.1186/s12985-017-0706-8,PMC5320732,28222808,CC BY,"BACKGROUND: In recent years, novel hepadnaviruses, hepeviruses, hepatoviruses, and hepaciviruses have been discovered in various species of bat around the world, indicating that bats may act as natural reservoirs for these hepatitis viruses. In order to further assess the distribution of hepatitis viruses in bat populations in China, we tested the presence of these hepatitis viruses in our archived bat liver samples that originated from several bat species and various geographical regions in China. METHODS: A total of 78 bat liver samples (involving two families, five genera, and 17 species of bat) were examined using nested or heminested reverse transcription PCR (RT-PCR) with degenerate primers. Full-length genomic sequences of two virus strains were sequenced followed by phylogenetic analyses. RESULTS: Four samples were positive for hepadnavirus, only one was positive for hepevirus, and none of the samples were positive for hepatovirus or hepacivirus. The hepadnaviruses were discovered in the horseshoe bats, Rhinolophus sinicus and Rhinolophus affinis, and the hepevirus was found in the whiskered bat Myotis davidii. The full-length genomic sequences were determined for one of the two hepadnaviruses identified in R. sinicus (designated BtHBVRs3364) and the hepevirus (designated BtHEVMd2350). A sequence identity analysis indicated that BtHBVRs3364 had the highest degree of identity with a previously reported hepadnavirus from the roundleaf bat, Hipposideros pomona, from China, and BtHEVMd2350 had the highest degree of identity with a hepevirus found in the serotine bat, Eptesicus serotinus, from Germany, but it exhibited high levels of divergence at both the nucleotide and the amino acid levels. CONCLUSIONS: This is the first study to report that the Chinese horseshoe bat and the Chinese whiskered bat have been found to carry novel hepadnaviruses and a novel hepevirus, respectively. The discovery of BtHBVRs3364 further supports the significance of host switches evolution while opposing the co-evolutionary theory associated with hepadnaviruses. According to the latest criterion of the International Committee on Taxonomy of Viruses (ICTV), we hypothesize that BtHEVMd2350 represents an independent genotype within the species Orthohepevirus D of the family Hepeviridae.",2017 Feb 22,"['Wang, Bo', 'Yang, Xing-Lou', 'Li, Wen', 'Zhu, Yan', 'Ge, Xing-Yi', 'Zhang, Li-Biao', 'Zhang, Yun-Zhi', 'Bock, Claus-Thomas', 'Shi, Zheng-Li']",Virol J,,,True
97f1fe02cd9244df3c903856dcb615d9fb6ec02a,PMC,"Interferon β-1a for the treatment of Ebola virus disease: A historically controlled, single-arm proof-of-concept trial",http://dx.doi.org/10.1371/journal.pone.0169255,PMC5321269,28225767,CC BY,"To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD). Based on our in vitro evidence of antiviral activity of interferon (IFN)-ß activity against Ebola virus, we conducted a single arm clinical study in Guinea to evaluate the safety and therapeutic efficacy of IFN β-1a treatment for EVD. Nine individuals infected with Ebola virus were treated with IFN β-1a and compared retrospectively with a matched cohort of 21 infected patients receiving standardized supportive care only during the same time period at the same treatment unit. Cognizant of the limitations of having treated only 9 individuals with EVD, the data collected are cautiously considered. When compared to supportive care only, IFN β-1a treatment seemed to facilitate viral clearance from the blood and appeared associated with earlier resolution of disease symptoms. Survival, calculated from the date of consent for those in the trial and date of admission from those in the control cohort, to the date of death, was 19% for those receiving supportive care only, compared to 67% for those receiving supportive care plus IFN β-1a. Given the differences in baseline blood viremia between the control cohort and the IFN-treated cohort, an additional 17 controls were included for a subset analysis, from other treatment units in Guinea, matched with the IFN-treated patients based on age and baseline blood viremia. Subset analyses using this expanded control cohort suggests that patients without IFN β-1a treatment were ~ 1.5–1.9 fold more likely to die than those treated. Viewed altogether the results suggest a rationale for further clinical evaluation of IFN β-1a.",2017 Feb 22,"['Konde, Mandy Kader', 'Baker, Darren P.', 'Traore, Fode Amara', 'Sow, Mamadou Saliou', 'Camara, Alioune', 'Barry, Alpha Amadou', 'Mara, Doussou', 'Barry, Abdoulaye', 'Cone, Moussa 3', 'Kaba, Ibrahima', 'Richard, Amento Ablam', 'Beavogui, Abdoul Habib', 'Günther, Stephan', None, 'Pintilie, Melania', 'Fish, Eleanor N.']",PLoS One,,,True
b420e61b7bad7118736507f69d3a255d5d171dea,PMC,"Interferon β-1a for the treatment of Ebola virus disease: A historically controlled, single-arm proof-of-concept trial",http://dx.doi.org/10.1371/journal.pone.0169255,PMC5321269,28225767,CC BY,"To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD). Based on our in vitro evidence of antiviral activity of interferon (IFN)-ß activity against Ebola virus, we conducted a single arm clinical study in Guinea to evaluate the safety and therapeutic efficacy of IFN β-1a treatment for EVD. Nine individuals infected with Ebola virus were treated with IFN β-1a and compared retrospectively with a matched cohort of 21 infected patients receiving standardized supportive care only during the same time period at the same treatment unit. Cognizant of the limitations of having treated only 9 individuals with EVD, the data collected are cautiously considered. When compared to supportive care only, IFN β-1a treatment seemed to facilitate viral clearance from the blood and appeared associated with earlier resolution of disease symptoms. Survival, calculated from the date of consent for those in the trial and date of admission from those in the control cohort, to the date of death, was 19% for those receiving supportive care only, compared to 67% for those receiving supportive care plus IFN β-1a. Given the differences in baseline blood viremia between the control cohort and the IFN-treated cohort, an additional 17 controls were included for a subset analysis, from other treatment units in Guinea, matched with the IFN-treated patients based on age and baseline blood viremia. Subset analyses using this expanded control cohort suggests that patients without IFN β-1a treatment were ~ 1.5–1.9 fold more likely to die than those treated. Viewed altogether the results suggest a rationale for further clinical evaluation of IFN β-1a.",2017 Feb 22,"['Konde, Mandy Kader', 'Baker, Darren P.', 'Traore, Fode Amara', 'Sow, Mamadou Saliou', 'Camara, Alioune', 'Barry, Alpha Amadou', 'Mara, Doussou', 'Barry, Abdoulaye', 'Cone, Moussa 3', 'Kaba, Ibrahima', 'Richard, Amento Ablam', 'Beavogui, Abdoul Habib', 'Günther, Stephan', None, 'Pintilie, Melania', 'Fish, Eleanor N.']",PLoS One,,,True
ff2b36ea32d849a577ae66637bbe359f108f35d8,PMC,"Analysis of spatial mobility in subjects from a Dengue endemic urban locality in Morelos State, Mexico",http://dx.doi.org/10.1371/journal.pone.0172313,PMC5321279,28225820,CC BY,"INTRODUCTION: Mathematical models and field data suggest that human mobility is an important driver for Dengue virus transmission. Nonetheless little is known on this matter due the lack of instruments for precise mobility quantification and study design difficulties. MATERIALS AND METHODS: We carried out a cohort-nested, case-control study with 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with the goal of describing human mobility patterns of recently Dengue virus-infected subjects, and comparing them with those of non-infected subjects living in an urban endemic locality. Mobility was quantified using a GPS-data logger registering waypoints at 60-second intervals for a minimum of 15 natural days. RESULTS: Although absolute displacement was highly biased towards the intradomestic and peridomestic areas, occasional displacements exceeding a 100-Km radius from the center of the studied locality were recorded for all three study groups and individual displacements were recorded traveling across six states from central Mexico. Additionally, cases had a larger number of visits out of the municipality´s administrative limits when compared to intradomestic controls (cases: 10.4 versus intradomestic controls: 2.9, p = 0.0282). We were able to identify extradomestic places within and out of the locality that were independently visited by apparently non-related infected subjects, consistent with houses, working and leisure places. CONCLUSIONS: Results of this study show that human mobility in a small urban setting exceeded that considered by local health authority’s administrative limits, and was different between recently infected and non-infected subjects living in the same household. These observations provide important insights about the role that human mobility may have in Dengue virus transmission and persistence across endemic geographic areas that need to be taken into account when planning preventive and control measures. Finally, these results are a valuable reference when setting the parameters for future mathematical modeling studies.",2017 Feb 22,"['Falcón-Lezama, Jorge Abelardo', 'Santos-Luna, René', 'Román-Pérez, Susana', 'Martínez-Vega, Ruth Aralí', 'Herrera-Valdez, Marco Arieli', 'Kuri-Morales, Ángel Fernando', 'Adams, Ben', 'Kuri-Morales, Pablo Antonio', 'López-Cervantes, Malaquías', 'Ramos-Castañeda, José']",PLoS One,,,True
ec057f679419810619852bd937fdab879a30e1ba,PMC,Prevalence and risk factors of chlamydia infection in Hong Kong: A population-based geospatial household survey and testing,http://dx.doi.org/10.1371/journal.pone.0172561,PMC5321413,28225805,CC BY,"BACKGROUND: Chlamydia causes infertility and increases risk of HIV infection, and population-based studies provide essential information for effective infection control and prevention. This study examined Chlamydia trachomatis prevalence and risk factors among a representative sample of 18-49-year-old residents in Hong Kong. METHODS: Census boundary map of 412 constituency areas was used as primary sampling units to construct the sampling frame and, residential buildings and units were randomly selected using geospatial modelling. A questionnaire on sexual practice and health was conducted, and polymerase chain reaction was used to test the urine for genital chlamydial infection. Invitation letters were sent to the selected households and a team of interviewers were sent to recruit one subject per household. Prevalence data was weighted according to the 2011 census and risk factors identified through logistic regression. RESULTS: Among 881 participants (response rate of 24.5%), the overall Chlamydia trachomatis prevalence was low at 1.4% (95%CI 0.8–2.5%) but sexually active young (18–26 years) women had relatively high prevalence (5.8%, 95%CI 1.7–18.2%) in Hong Kong. A unique U-shape disease burden was observed with peaks in younger and older (40–49 years) women. Amongst the sexually active women, the risk factors of Chlamydia trachomatis infection were: younger age (aOR = 25.4, 95% CI 2.81–230); living alone (aOR = 8.99, 95% CI 1.46–55.40); and, among all the sexually active participants, males (including the male partners of the female participants) who had travelled out of Hong Kong in the previous 12 months had higher risks of infection (aOR = 5.35; 95% CI 1.25–22.8). A core-peripheral geographical distribution of Chlamydia trachomatis prevalence was also observed. CONCLUSION: Young and older sexually active women in Hong Kong have high prevalence of chlamydia. Routine screening for sexually active women and young men should be considered. Further research on testing feasibility and linkage-to-care are urgently needed to control the infection.",2017 Feb 22,"['Wong, William Chi Wai', 'Zhao, Yanping', 'Wong, Ngai Sze', 'Parish, William L.', 'Miu, Heidi Yin Hai', 'Yang, Li-Gang', 'Emch, Michael', 'Ho, King Man', 'Fong, Francois Yeung', 'Tucker, Joseph D.']",PLoS One,,,True
c53d3d043454289602f4177bb5125ef3d9d0df38,PMC,"An outbreak of acute respiratory disease caused by a virus associated RNA II gene mutation strain of human adenovirus 7 in China, 2015",http://dx.doi.org/10.1371/journal.pone.0172519,PMC5321423,28225804,CC BY,"Human adenovirus 7 (HAdV-7) strains are a major cause of acute respiratory disease (ARD) among adults and children, associated with fatal pneumonia. An ARD outbreak caused by HAdV-7 that involved 739 college students was reported in this article. To better understand the underlying cause of this large-scale epidemic, virus strains were isolated from infected patients and sequence variations of the whole genome sequence were detected. Evolutionary trees and alignment results indicated that the major capsid protein genes hexon and fibre were strongly conserved among serotype 7 strains in China at that time. Instead, the HAdV-7 strains presented three thymine deletions in the virus associated RNA (VA RNA) II terminal region. We also found that the mutation might lead to increased mRNA expression of an adjacent gene, L1 52/55K, and thus promoted faster growth. These findings suggest that sequence variation of VA RNA II gene was a potential cause of such a severe HAdV-7 infection and this gene should be a new-emerging factor to be monitored for better understanding of HAdV-7 infection.",2017 Feb 22,"['Yang, Xiaoxia', 'Wang, Qiongshu', 'Liang, Beibei', 'Wu, Fuli', 'Li, Hao', 'Liu, Hongbo', 'Sheng, Chunyu', 'Ma, Qiuxia', 'Yang, Chaojie', 'Xie, Jing', 'Li, Peng', 'Jia, Leili', 'Wang, Ligui', 'Du, Xinying', 'Qiu, Shaofu', 'Song, Hongbin']",PLoS One,,,True
b87033ed15a4d9f337f37d67516b49992fd923c4,PMC,Specific and Novel microRNAs Are Regulated as Response to Fungal Infection in Human Dendritic Cells,http://dx.doi.org/10.3389/fmicb.2017.00270,PMC5322194,28280489,CC BY,"Within the last two decades, the incidence of invasive fungal infections has been significantly increased. They are characterized by high mortality rates and are often caused by Candida albicans and Aspergillus fumigatus. The increasing number of infections underlines the necessity for additional anti-fungal therapies, which require extended knowledge of gene regulations during fungal infection. MicroRNAs are regulators of important cellular processes, including the immune response. By analyzing their regulation and impact on target genes, novel therapeutic and diagnostic approaches may be developed. Here, we examine the role of microRNAs in human dendritic cells during fungal infection. Dendritic cells represent the bridge between the innate and the adaptive immune systems. Therefore, analysis of gene regulation of dendritic cells is of particular significance. By applying next-generation sequencing of small RNAs, we quantify microRNA expression in monocyte-derived dendritic cells after 6 and 12 h of infection with C. albicans and A. fumigatus as well as treatment with lipopolysaccharides (LPS). We identified 26 microRNAs that are differentially regulated after infection by the fungi or LPS. Three and five of them are specific for fungal infections after 6 and 12 h, respectively. We further validated interactions of miR-132-5p and miR-212-5p with immunological relevant target genes, such as FKBP1B, KLF4, and SPN, on both RNA and protein level. Our results indicate that these microRNAs fine-tune the expression of immune-related target genes during fungal infection. Beyond that, we identified previously undiscovered microRNAs. We validated three novel microRNAs via qRT-PCR. A comparison with known microRNAs revealed possible relations with the miR-378 family and miR-1260a/b for two of them, while the third one features a unique sequence with no resemblance to known microRNAs. In summary, this study analyzes the effect of known microRNAs in dendritic cells during fungal infections and proposes novel microRNAs that could be experimentally verified.",2017 Feb 23,"['Dix, Andreas', 'Czakai, Kristin', 'Leonhardt, Ines', 'Schäferhoff, Karin', 'Bonin, Michael', 'Guthke, Reinhard', 'Einsele, Hermann', 'Kurzai, Oliver', 'Löffler, Jürgen', 'Linde, Jörg']",Front Microbiol,,,True
2943228f12c0cb46c035893d848410ff23686595,PMC,Epitope Addition and Ablation via Manipulation of a Dengue Virus Serotype 1 Infectious Clone,http://dx.doi.org/10.1128/mSphere.00380-16,PMC5322348,28251184,CC BY,"Despite the clinical relevance, dengue virus (DENV) research has been hampered by the absence of robust reverse genetic systems to manipulate the viral serotypes for propagation and generation of mutant viruses. In this article, we describe application of an infectious clone system for DENV serotype 1 (DENV1). Similar to previous clones in both flaviviruses and coronaviruses, the approach constructs a panel of contiguous cDNAs that span the DENV genome and can be systematically and directionally assembled to produce viable, full-length viruses. Comparison of the virus derived from the infectious clone with the original viral isolate reveals identical sequence, comparable endpoint titers, and similar focus staining. Both focus-forming assays and percent infection by flow cytometry revealed overlapping replication levels in two different cell types. Moreover, serotype-specific monoclonal antibodies (MAbs) bound similarly to infectious clone and the natural isolate. Using the clone, we were able to insert a DENV4 type-specific epitope recognized by primate MAb 5H2 into envelope (E) protein domain I (EDI) of DENV1 and recover a viable chimeric recombinant virus. The recombinant DENV1 virus was recognized and neutralized by the DENV4 type-specific 5H2 MAb. The introduction of the 5H2 epitope ablated two epitopes on DENV1 EDI recognized by human MAbs (1F4 and 14C10) that strongly neutralize DENV1. Together, the work demonstrates the utility of the infectious clone and provides a resource to rapidly manipulate the DENV1 serotype for generation of recombinant and mutant viruses. IMPORTANCE Dengue viruses (DENVs) are significant mosquito-transmitted pathogens that cause widespread infection and can lead to severe infection and complications. Here we further characterize a novel and robust DENV serotype 1 (DENV1) infectious clone system that can be used to support basic and applied research. We demonstrate how the system can be used to probe the antigenic relationships between strains by creating viable recombinant viruses that display or lack major antibody epitopes. The DENV1 clone system and recombinant viruses can be used to analyze existing vaccine immune responses and inform second-generation bivalent vaccine designs.",2017 Feb 22,"['Gallichotte, Emily N.', 'Menachery, Vineet D.', 'Yount, Boyd L.', 'Widman, Douglas G.', 'Dinnon, Kenneth H.', 'Hartman, Steven', 'de Silva, Aravinda M.', 'Baric, Ralph S.']",mSphere,,,True
2a6a8442d3a45cdaded7efe018f2c400ceabf0c2,PMC,Epitope Addition and Ablation via Manipulation of a Dengue Virus Serotype 1 Infectious Clone,http://dx.doi.org/10.1128/mSphere.00380-16,PMC5322348,28251184,CC BY,"Despite the clinical relevance, dengue virus (DENV) research has been hampered by the absence of robust reverse genetic systems to manipulate the viral serotypes for propagation and generation of mutant viruses. In this article, we describe application of an infectious clone system for DENV serotype 1 (DENV1). Similar to previous clones in both flaviviruses and coronaviruses, the approach constructs a panel of contiguous cDNAs that span the DENV genome and can be systematically and directionally assembled to produce viable, full-length viruses. Comparison of the virus derived from the infectious clone with the original viral isolate reveals identical sequence, comparable endpoint titers, and similar focus staining. Both focus-forming assays and percent infection by flow cytometry revealed overlapping replication levels in two different cell types. Moreover, serotype-specific monoclonal antibodies (MAbs) bound similarly to infectious clone and the natural isolate. Using the clone, we were able to insert a DENV4 type-specific epitope recognized by primate MAb 5H2 into envelope (E) protein domain I (EDI) of DENV1 and recover a viable chimeric recombinant virus. The recombinant DENV1 virus was recognized and neutralized by the DENV4 type-specific 5H2 MAb. The introduction of the 5H2 epitope ablated two epitopes on DENV1 EDI recognized by human MAbs (1F4 and 14C10) that strongly neutralize DENV1. Together, the work demonstrates the utility of the infectious clone and provides a resource to rapidly manipulate the DENV1 serotype for generation of recombinant and mutant viruses. IMPORTANCE Dengue viruses (DENVs) are significant mosquito-transmitted pathogens that cause widespread infection and can lead to severe infection and complications. Here we further characterize a novel and robust DENV serotype 1 (DENV1) infectious clone system that can be used to support basic and applied research. We demonstrate how the system can be used to probe the antigenic relationships between strains by creating viable recombinant viruses that display or lack major antibody epitopes. The DENV1 clone system and recombinant viruses can be used to analyze existing vaccine immune responses and inform second-generation bivalent vaccine designs.",2017 Feb 22,"['Gallichotte, Emily N.', 'Menachery, Vineet D.', 'Yount, Boyd L.', 'Widman, Douglas G.', 'Dinnon, Kenneth H.', 'Hartman, Steven', 'de Silva, Aravinda M.', 'Baric, Ralph S.']",mSphere,,,False
8f366ef1bf6f6bb156921c984ef62dafe034bc5f,PMC,Epitope Addition and Ablation via Manipulation of a Dengue Virus Serotype 1 Infectious Clone,http://dx.doi.org/10.1128/mSphere.00380-16,PMC5322348,28251184,CC BY,"Despite the clinical relevance, dengue virus (DENV) research has been hampered by the absence of robust reverse genetic systems to manipulate the viral serotypes for propagation and generation of mutant viruses. In this article, we describe application of an infectious clone system for DENV serotype 1 (DENV1). Similar to previous clones in both flaviviruses and coronaviruses, the approach constructs a panel of contiguous cDNAs that span the DENV genome and can be systematically and directionally assembled to produce viable, full-length viruses. Comparison of the virus derived from the infectious clone with the original viral isolate reveals identical sequence, comparable endpoint titers, and similar focus staining. Both focus-forming assays and percent infection by flow cytometry revealed overlapping replication levels in two different cell types. Moreover, serotype-specific monoclonal antibodies (MAbs) bound similarly to infectious clone and the natural isolate. Using the clone, we were able to insert a DENV4 type-specific epitope recognized by primate MAb 5H2 into envelope (E) protein domain I (EDI) of DENV1 and recover a viable chimeric recombinant virus. The recombinant DENV1 virus was recognized and neutralized by the DENV4 type-specific 5H2 MAb. The introduction of the 5H2 epitope ablated two epitopes on DENV1 EDI recognized by human MAbs (1F4 and 14C10) that strongly neutralize DENV1. Together, the work demonstrates the utility of the infectious clone and provides a resource to rapidly manipulate the DENV1 serotype for generation of recombinant and mutant viruses. IMPORTANCE Dengue viruses (DENVs) are significant mosquito-transmitted pathogens that cause widespread infection and can lead to severe infection and complications. Here we further characterize a novel and robust DENV serotype 1 (DENV1) infectious clone system that can be used to support basic and applied research. We demonstrate how the system can be used to probe the antigenic relationships between strains by creating viable recombinant viruses that display or lack major antibody epitopes. The DENV1 clone system and recombinant viruses can be used to analyze existing vaccine immune responses and inform second-generation bivalent vaccine designs.",2017 Feb 22,"['Gallichotte, Emily N.', 'Menachery, Vineet D.', 'Yount, Boyd L.', 'Widman, Douglas G.', 'Dinnon, Kenneth H.', 'Hartman, Steven', 'de Silva, Aravinda M.', 'Baric, Ralph S.']",mSphere,,,False
fe37af79d60f91fbe23eda247a4dbbc05f7d9402,PMC,Epitope Addition and Ablation via Manipulation of a Dengue Virus Serotype 1 Infectious Clone,http://dx.doi.org/10.1128/mSphere.00380-16,PMC5322348,28251184,CC BY,"Despite the clinical relevance, dengue virus (DENV) research has been hampered by the absence of robust reverse genetic systems to manipulate the viral serotypes for propagation and generation of mutant viruses. In this article, we describe application of an infectious clone system for DENV serotype 1 (DENV1). Similar to previous clones in both flaviviruses and coronaviruses, the approach constructs a panel of contiguous cDNAs that span the DENV genome and can be systematically and directionally assembled to produce viable, full-length viruses. Comparison of the virus derived from the infectious clone with the original viral isolate reveals identical sequence, comparable endpoint titers, and similar focus staining. Both focus-forming assays and percent infection by flow cytometry revealed overlapping replication levels in two different cell types. Moreover, serotype-specific monoclonal antibodies (MAbs) bound similarly to infectious clone and the natural isolate. Using the clone, we were able to insert a DENV4 type-specific epitope recognized by primate MAb 5H2 into envelope (E) protein domain I (EDI) of DENV1 and recover a viable chimeric recombinant virus. The recombinant DENV1 virus was recognized and neutralized by the DENV4 type-specific 5H2 MAb. The introduction of the 5H2 epitope ablated two epitopes on DENV1 EDI recognized by human MAbs (1F4 and 14C10) that strongly neutralize DENV1. Together, the work demonstrates the utility of the infectious clone and provides a resource to rapidly manipulate the DENV1 serotype for generation of recombinant and mutant viruses. IMPORTANCE Dengue viruses (DENVs) are significant mosquito-transmitted pathogens that cause widespread infection and can lead to severe infection and complications. Here we further characterize a novel and robust DENV serotype 1 (DENV1) infectious clone system that can be used to support basic and applied research. We demonstrate how the system can be used to probe the antigenic relationships between strains by creating viable recombinant viruses that display or lack major antibody epitopes. The DENV1 clone system and recombinant viruses can be used to analyze existing vaccine immune responses and inform second-generation bivalent vaccine designs.",2017 Feb 22,"['Gallichotte, Emily N.', 'Menachery, Vineet D.', 'Yount, Boyd L.', 'Widman, Douglas G.', 'Dinnon, Kenneth H.', 'Hartman, Steven', 'de Silva, Aravinda M.', 'Baric, Ralph S.']",mSphere,,,False
0d76724747e4dd9c957017bb1dd628f087f652a3,PMC,Incorporating one health into medical education,http://dx.doi.org/10.1186/s12909-017-0883-6,PMC5322638,28228144,CC BY,"One Health is an emerging concept that stresses the linkages between human, animal, and environmental health, as well as the need for interdisciplinary communication and collaboration to address health issues including emerging zoonotic diseases, climate change impacts, and the human-animal bond. It promotes complex problem solving using a systems framework that considers interactions between humans, animals, and their shared environment. While many medical educators may not yet be familiar with the concept, the One Health approach has been endorsed by a number of major medical and public health organizations and is beginning to be implemented in a number of medical schools. In the research setting, One Health opens up new avenues to understand, detect, and prevent emerging infectious diseases, and also to conduct translational studies across species. In the clinical setting, One Health provides practical ways to incorporate environmental and animal contact considerations into patient care. This paper reviews clinical and research aspects of the One Health approach through an illustrative case updating the biopsychosocial model and proposes a basic set of One Health competencies for training and education of human health care providers.",2017 Feb 23,"['Rabinowitz, Peter M.', 'Natterson-Horowitz, Barbara J.', 'Kahn, Laura H.', 'Kock, Richard', 'Pappaioanou, Marguerite']",BMC Med Educ,,,True
be12dac627e0584817ed6fbb4a7b154cc6fb304a,PMC,"An examination of the factorial and convergent validity of four measures of conspiracist ideation, with recommendations for researchers",http://dx.doi.org/10.1371/journal.pone.0172617,PMC5322923,28231266,CC BY,"A number scales have been developed to measure conspiracist ideation, but little attention has been paid to the factorial validity of these scales. We reassessed the psychometric properties of four widely-used scales, namely the Belief in Conspiracy Theories Inventory (BCTI), the Conspiracy Mentality Questionnaire (CMQ), the Generic Conspiracist Beliefs Scale (GCBS), and the One-Item Conspiracy Measure (OICM). Eight-hundred-and-three U.S. adults completed all measures, along with measures of endorsement of 9/11 and anti-vaccination conspiracy theories. Through both exploratory and confirmatory factor analysis, we found that only the BCTI had acceptable factorial validity. We failed to confirm the factor structures of the CMQ and the GBCS, suggesting these measures had poor factorial validity. Indices of convergent validity were acceptable for the BCTI, but weaker for the other measures. Based on these findings, we provide suggestions for the future refinement in the measurement of conspiracist ideation.",2017 Feb 23,"['Swami, Viren', 'Barron, David', 'Weis, Laura', 'Voracek, Martin', 'Stieger, Stefan', 'Furnham, Adrian']",PLoS One,,,True
c6bfe832f2dd36a5c86f548138c96883ce0f46b7,PMC,The pathogens profile in children with otitis media with effusion and adenoid hypertrophy,http://dx.doi.org/10.1371/journal.pone.0171049,PMC5322954,28231295,CC BY,"OBJECTIVES: To evaluate the presence of viruses and bacteria in middle ear and adenoids of patients with and without otitis media with effusion (OME). METHODS: Adenoid samples and middle ear washes (MEW) were obtained from children with OME associated with adenoid hypertrophy undergoing adenoidectomy and tympanostomy, and compared to those obtained from patients undergoing cochlear implant surgery, as a control group. Specific DNA or RNA of 9 respiratory viruses (rhinovirus, influenza virus, picornavirus, syncytial respiratory virus, metapneumovirus, coronavirus, enterovirus, adenovirus and bocavirus) and 5 bacteria (S. pneumoniae, H. influenzae, M. catarrhalis, P. aeruginosa and S. aureus) were extracted and quantified by real-time PCR. RESULTS: 37 OME and 14 cochlear implant children were included in the study. At the adenoid, virus and bacteria were similarly detected in both OME and control patients. At the middle ear washes, however, a higher prevalence of bacteria was observed in patients with OME (p = 0.01). S. pneumoniae (p = 0.01) and M. catarrhalis (p = 0.022) were the bacteria responsible for this difference. Although total virus detection was not statistically different from controls at the middle ear washes (p = 0.065), adenovirus was detected in higher proportions in adenoid samples of OME patients than controls (p = 0.019). CONCLUSIONS: Despite both OME and control patients presented similar rates of viruses and bacteria at the adenoid, children with OME presented higher prevalence of S. pneumonia, M. catarrhalis in middle ear and adenovirus in adenoids when compared to controls. These findings could suggest that these pathogens could contribute to the fluid persistence in the middle ear.",2017 Feb 23,"['Buzatto, G. P.', 'Tamashiro, E.', 'Proenca-Modena, J. L.', 'Saturno, T. H.', 'Prates, M. C.', 'Gagliardi, T. B.', 'Carenzi, L. R.', 'Massuda, E. T.', 'Hyppolito, M. A.', 'Valera, F. C. P.', 'Arruda, E.', 'Anselmo-Lima, W. T.']",PLoS One,,,True
e7124df42078edba08ccba1b033dffb0a36f6305,PMC,Mosquito cell-derived West Nile virus replicon particles mimic arbovirus inoculum and have reduced spread in mice,http://dx.doi.org/10.1371/journal.pntd.0005394,PMC5322982,28187142,CC BY,"Half of the human population is at risk of infection by an arthropod-borne virus. Many of these arboviruses, such as West Nile, dengue, and Zika viruses, infect humans by way of a bite from an infected mosquito. This infectious inoculum is insect cell-derived giving the virus particles distinct qualities not present in secondary infectious virus particles produced by infected vertebrate host cells. The insect cell-derived particles differ in the glycosylation of virus structural proteins and the lipid content of the envelope, as well as their induction of cytokines. Thus, in order to accurately mimic the inoculum delivered by arthropods, arboviruses should be derived from arthropod cells. Previous studies have packaged replicon genome in mammalian cells to produce replicon particles, which undergo only one round of infection, but no studies exist packaging replicon particles in mosquito cells. Here we optimized the packaging of West Nile virus replicon genome in mosquito cells and produced replicon particles at high concentration, allowing us to mimic mosquito cell-derived viral inoculum. These particles were mature with similar genome equivalents-to-infectious units as full-length West Nile virus. We then compared the mosquito cell-derived particles to mammalian cell-derived particles in mice. Both replicon particles infected skin at the inoculation site and the draining lymph node by 3 hours post-inoculation. The mammalian cell-derived replicon particles spread from the site of inoculation to the spleen and contralateral lymph nodes significantly more than the particles derived from mosquito cells. This in vivo difference in spread of West Nile replicons in the inoculum demonstrates the importance of using arthropod cell-derived particles to model early events in arboviral infection and highlights the value of these novel arthropod cell-derived replicon particles for studying the earliest virus-host interactions for arboviruses.",2017 Feb 10,"['Boylan, Brendan T.', 'Moreira, Fernando R.', 'Carlson, Tim W.', 'Bernard, Kristen A.']",PLoS Negl Trop Dis,,,True
9809fd94325b39bffb3a2414a3d7f3e1429fa539,PMC,Global toxocariasis research trends from 1932 to 2015: a bibliometric analysis,http://dx.doi.org/10.1186/s12961-017-0178-8,PMC5324285,28231792,CC BY,"BACKGROUND: Toxocariasis is a highly prevalent parasitic disease in the tropical regions of the world, with its impact on public health being typically underestimated. To better recognise the trends and characteristics of toxocariasis research, this study is a bibliometric analysis of the global toxocariasis research. METHODS: Searches were completed on April 5, 2016, using the Scopus database. A search without any language restriction was performed to extract publications dealing with toxocariasis. Terms related to toxocariasis were used to perform a title keyword search. RESULTS: A total of 2765 publications comprising 11 document types and published between 1932 and 2015 were included in the analysis. Articles were the most popular document form, accounting for 83.62% of all publications, followed by letters (3.80%) and reviews (3.4%). The annual number of research publications increased from 30 in 1980 to 111 in 2015, indicating that the number of publications on toxocariasis has increased slowly over the past 35 years. The United States of America and Japan are the predominant countries of origin, with 303 articles and 207 articles, respectively, followed by Brazil and the United Kingdom, with 180 (6.5%) each. The h-index for all the publications was 60. The highest h-index were for publications from the United Kingdom (h-index value = 43) and the United States (h-index value = 39); these two countries were also involved with the highest number of international collaborations, with 27 and 28 countries, respectively. CONCLUSIONS: Developed countries, including the United States, Japan, the United Kingdom, France, Germany and Italy, are the world’s leaders in toxocariasis research, contributing to more than 34% of the total published literature. In addition, developing countries, such as Brazil, Poland, Argentina and India, showed a noticeable increase in published papers on toxocariasis research in recent years. A push for more collaboration is needed to achieve a superior research strategy related to toxocariasis at the global level from the viewpoint of epidemiological data, clinical aspects, medical ecology, molecular aspects and treatment practices associated with toxocariasis.",2017 Feb 23,"Zyoud, Sa’ed H.",Health Res Policy Syst,,,True
2f38b7690f9e7ab1069f6b9e28c103de5f6adb96,PMC,"Lyssaviruses and rabies: current conundrums, concerns, contradictions and controversies",http://dx.doi.org/10.12688/f1000research.10416.1,PMC5325067,28299201,CC BY,"Lyssaviruses are bullet-shaped, single-stranded, negative-sense RNA viruses and the causative agents of the ancient zoonosis rabies. Africa is the likely home to the ancestors of taxa residing within the Genus Lyssavirus, Family Rhabdoviridae. Diverse lyssaviruses are envisioned as co-evolving with bats, as the ultimate reservoirs, over seemingly millions of years. In terms of relative distribution, overt abundance, and resulting progeny, rabies virus is the most successful lyssavirus species today, but for unknown reasons. All mammals are believed to be susceptible to rabies virus infection. Besides reservoirs among the Chiroptera, meso-carnivores also serve as major historical hosts and are represented among the canids, raccoons, skunks, mongooses, and ferret badgers.  Perpetuating as a disease of nature with the mammalian central nervous system as niche, host breadth alone precludes any candidacy for true eradication. Despite having the highest case fatality of any infectious disease and a burden in excess of or comparative to other major zoonoses, rabies remains neglected. Once illness appears, no treatment is proven to prevent death. Paradoxically, vaccines were developed more than a century ago, but the clear majority of human cases are unvaccinated. Tens of millions of people are exposed to suspect rabid animals and tens of thousands succumb annually, primarily children in developing countries, where canine rabies is enzootic. Rather than culling animal populations, one of the most cost-effective strategies to curbing human fatalities is the mass vaccination of dogs. Building on considerable progress to date, several complementary actions are needed in the near future, including a more harmonized approach to viral taxonomy, enhanced de-centralized laboratory-based surveillance, focal pathogen discovery and characterization, applied pathobiological research for therapeutics, improved estimates of canine populations at risk, actual production of required vaccines and related biologics, strategies to maximize prevention but minimize unnecessary human prophylaxis, and a long-term, realistic plan for sustained global program support to achieve success in disease control, prevention, and elimination.",2017 Feb 23,"['Rupprecht, Charles', 'Kuzmin, Ivan', 'Meslin, Francois']",F1000Res,,,True
fe7d921c5fbcd19fd95d17f31eb4149a5dfe2ae6,PMC,"The relationship of serum vitamins A, D, E and LL-37 levels with allergic status, tonsillar virus detection and immune response",http://dx.doi.org/10.1371/journal.pone.0172350,PMC5325266,28235040,CC BY,"BACKGROUND: Tonsils have an active role in immune defence and inducing and maintaining tolerance to allergens. Vitamins A, D, and E, and antimicrobial peptide LL-37 may have immunomodulatory effects. We studied how their serum levels were associated with allergy status, intratonsillar/nasopharyngeal virus detection and intratonsillar expression of T cell- and innate immune response-specific cytokines, transcription factors and type I/II/III interferons in patients undergoing tonsillectomy. METHODS: 110 elective tonsillectomy patients participated. Serum levels of vitamins A, 25(OH)D, and E, LL-37 and allergen-specific IgE as well as nasopharyngeal/intratonsillar respiratory viruses were analyzed. The mRNA expression of IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2 and Tbet in tonsils were analyzed by quantitative RT-PCR. RESULTS: The median age of the patients was 16 years (range 3–60), 28% of subjects had atopy, and 57% carried ≥1 respiratory virus in nasopharynx. Detection of viruses decreased by age. Higher vitamin A levels showed borderline significance with less viral detection (P = 0.056). Higher 25(OH)D was associated with less allergic rhinitis and atopy (P < 0.05) and higher vitamin E with less self-reported allergy (P < 0.05). In gene expression analyses, 25(OH)D was associated with higher IL-37, vitamin A with higher IFN-γ and vitamin E with less IL-28 (P < 0.05). LL-37 was associated with less FOXP3, RORC2 and IL-17 in tonsils (P < 0.05). CONCLUSIONS: Vitamin D and E levels were associated with less allergic disorders. Vitamin A was linked to antiviral and vitamin D with anti-inflammatory activity. LL-37 and was linked to T regulatory cell effects.",2017 Feb 24,"['Elenius, Varpu', 'Palomares, Oscar', 'Waris, Matti', 'Turunen, Riitta', 'Puhakka, Tuomo', 'Rückert, Beate', 'Vuorinen, Tytti', 'Allander, Tobias', 'Vahlberg, Tero', 'Akdis, Mübeccel', 'Camargo, Carlos A.', 'Akdis, Cezmi A.', 'Jartti, Tuomas']",PLoS One,,,True
e90d316cde320ab2cecb088c9242a9ef3766718c,PMC,Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography,http://dx.doi.org/10.1371/journal.pone.0172256,PMC5325310,28235014,CC BY,"We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose.",2017 Feb 24,"['Gerritsen, M. G.', 'Willemink, M. J.', 'Pompe, E.', 'van der Bruggen, T.', 'van Rhenen, A.', 'Lammers, J. W. J.', 'Wessels, F.', 'Sprengers, R. W.', 'de Jong, P. A.', 'Minnema, M. C.']",PLoS One,,,True
2f09116d82b287cf3731d3baacc75895e7999203,PMC,Comparative pathology of rhesus macaque and common marmoset animal models with Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1371/journal.pone.0172093,PMC5325479,28234937,CC BY,"Middle East respiratory syndrome (MERS), which is caused by a newly discovered coronavirus (CoV), has recently emerged. It causes severe viral pneumonia and is associated with a high fatality rate. However, the pathogenesis, comparative pathology and inflammatory cell response of rhesus macaques and common marmosets experimentally infected with MERS-CoV are unknown. We describe the histopathological, immunohistochemical, and ultrastructural findings from rhesus macaque and common marmoset animal models of MERS-CoV infection. The main histopathological findings in the lungs of rhesus macaques and common marmosets were varying degrees of pulmonary lesions, including pneumonia, pulmonary oedema, haemorrhage, degeneration and necrosis of the pneumocytes and bronchial epithelial cells, and inflammatory cell infiltration. The characteristic inflammatory cells in the lungs of rhesus macaques and common marmosets were eosinophils and neutrophils, respectively. Based on these observations, the lungs of rhesus macaques and common marmosets appeared to develop chronic and acute pneumonia, respectively. MERS-CoV antigens and viral RNA were identified in type I and II pneumocytes, alveolar macrophages and bronchial epithelial cells, and ultrastructural observations showed that viral protein was found in type II pneumocytes and inflammatory cells in both species. Correspondingly, the entry receptor DDP4 was found in type I and II pneumocytes, bronchial epithelial cells, and alveolar macrophages. The rhesus macaque and common marmoset animal models of MERS-CoV can be used as a tool to mimic the oncome of MERS-CoV infections in humans. These models can help to provide a better understanding of the pathogenic process of this virus and to develop effective medications and prophylactic treatments.",2017 Feb 24,"['Yu, Pin', 'Xu, Yanfeng', 'Deng, Wei', 'Bao, Linlin', 'Huang, Lan', 'Xu, Yuhuan', 'Yao, Yanfeng', 'Qin, Chuan']",PLoS One,,,True
a9467bbfc6a67f8a76ac8242a14207676d03c041,PMC,"Usefulness of multiplex PCR methods and respiratory viruses’ distribution in children below 15 years old according to age, seasons and clinical units in France: A 3 years retrospective study",http://dx.doi.org/10.1371/journal.pone.0172809,PMC5325537,28235002,CC BY,"BACKGROUND: To date, only influenza and RSV testing are recommended for respiratory viruses’ detection in paediatric units. In this study, we described, according to seasons, ages and clinical units, the results obtained in children (<15 years old) by multiplex-PCR (mPCR) tests allowing a quick and wide range detection of all respiratory viruses. These results were also compared with RSV specific detection. METHODS: All nasopharyngeal mPCR and RSV tests requested by clinicians in our French teaching hospitals group between 2011 and 2014 were retrospectively included. All repeated samples for the same children in the same month were discarded. RESULTS: Of the 381 mPCR tests (344 children) performed, 51.4% were positive. Positivity and viral co-infection rates were higher in the 6–36 months old strata (81% and 25%, p<0.0001 and p = 0.04, respectively). Viral distribution showed strong variations across ages. During specific influenza epidemic periods, only 1/39 (2.5%) mPCR tests were positive for influenza and 19/39 (48.7%) for other viruses. During specific RSV epidemic periods, only 8/46 (17.4%) mPCR tests were positive for RSV and 14/46 (30.4%) for other viruses. 477/1529 (31.2%) of RSV immunochromatography-tests were positive. Among the negatives immunochromatography-test also explored by mPCR, 28/62 (31%) were positive for other respiratory viruses. CONCLUSION: This study provides a wide description of respiratory viruses’ distribution among children in hospital settings using mPCR over 3 years. It emphasizes the number of undiagnosed respiratory viruses according to the current diagnosis practice in France and gives a better picture of respiratory viruses identified in hospital settings by mPCR all over the year in France.",2017 Feb 24,"['Visseaux, Benoit', 'Collin, Gilles', 'Ichou, Houria', 'Charpentier, Charlotte', 'Bendhafer, Samia', 'Dumitrescu, Madalina', 'Allal, Lahcene', 'Cojocaru, Bogdan', 'Desfrère, Luc', 'Descamps, Diane', 'Mandelbrot, Laurent', 'Houhou-Fidouh, Nadhira']",PLoS One,,,True
3ee0905adb62aaf5fc29019aac6add9ef862bb22,PMC,Electron microscopy studies of the coronavirus ribonucleoprotein complex,http://dx.doi.org/10.1007/s13238-016-0352-8,PMC5326623,28044277,CC BY,,2017 Mar 2,"['Gui, Miao', 'Liu, Xin', 'Guo, Deyin', 'Zhang, Zhen', 'Yin, Chang-Cheng', 'Chen, Yu', 'Xiang, Ye']",Protein Cell,,,True
7d5094e206f1773dc21d879809ddb1a7fccaa2ba,PMC,Electron microscopy studies of the coronavirus ribonucleoprotein complex,http://dx.doi.org/10.1007/s13238-016-0352-8,PMC5326623,28044277,CC BY,,2017 Mar 2,"['Gui, Miao', 'Liu, Xin', 'Guo, Deyin', 'Zhang, Zhen', 'Yin, Chang-Cheng', 'Chen, Yu', 'Xiang, Ye']",Protein Cell,,,True
743ca1ab0d309c7904b737c78985687e594a04cc,PMC,"Emerging and Neglected Infectious Diseases: Insights, Advances, and Challenges",http://dx.doi.org/10.1155/2017/5245021,PMC5327784,28286767,CC BY,"Infectious diseases are a significant burden on public health and economic stability of societies all over the world. They have for centuries been among the leading causes of death and disability and presented growing challenges to health security and human progress. The threat posed by infectious diseases is further deepened by the continued emergence of new, unrecognized, and old infectious disease epidemics of global impact. Over the past three and half decades at least 30 new infectious agents affecting humans have emerged, most of which are zoonotic and their origins have been shown to correlate significantly with socioeconomic, environmental, and ecological factors. As these factors continue to increase, putting people in increased contact with the disease causing pathogens, there is concern that infectious diseases may continue to present a formidable challenge. Constant awareness and pursuance of effective strategies for controlling infectious diseases and disease emergence thus remain crucial. This review presents current updates on emerging and neglected infectious diseases and highlights the scope, dynamics, and advances in infectious disease management with particular focus on WHO top priority emerging infectious diseases (EIDs) and neglected tropical infectious diseases.",2017 Feb 13,"Nii-Trebi, Nicholas Israel",Biomed Res Int,,,True
64c3ee477952b5dd96e786d2c9695e76953b03b5,PMC,Therapeutic antibodies for infectious diseases,http://dx.doi.org/10.2471/BLT.16.178061,PMC5328111,28250538,CC BY,,2017 Mar 1,"['Sparrow, Erin', 'Friede, Martin', 'Sheikh, Mohamud', 'Torvaldsen, Siranda']",Bull World Health Organ,,,True
be99996c561fe43928f9914548fcd3a49563ade0,PMC,Do medical students receive training in correct use of personal protective equipment?,http://dx.doi.org/10.1080/10872981.2017.1264125,PMC5328330,28178912,CC BY,"Background: Healthcare personnel often use incorrect technique for donning and doffing of personal protective equipment (PPE). Objective: We tested the hypothesis that medical students receive insufficient training on correct methods for donning and doffing PPE. Methods: We conducted a cross-sectional survey of medical students on clinical rotations at two teaching hospitals to determine the type of training they received in PPE technique. The students performed simulations of contaminated PPE removal with fluorescent lotion on gloves and were assessed for correct PPE technique and skin and/or clothing contamination. To obtain additional information on PPE training during medical education, residents, fellows, and attending physicians completed written questionnaires on PPE training received during medical school and on knowledge of PPE protocols recommended by the Centers for Disease Control and Prevention. Results: Of 27 medical students surveyed, only 11 (41%) reported receiving PPE training, and none had received training requiring demonstration of proficiency. During simulations, 25 of 27 (92.5%) students had one or more lapses in technique and 12 (44%) contaminated their skin with fluorescent lotion. For 100 residents, fellows and attending physicians representing 67 different medical schools, only 53% reported receiving training in use of PPE and only 39% selected correct donning and doffing sequence. Conclusions: Our findings suggest that there is a need for development of effective strategies to train medical students in correct use of PPE. Abbreviations: PPE: Personal protective equipment; MRSA: Methicillin-resistant Staphylococcus aureus; SARS: Severe acute respiratory syndrome; MERS: Middle East respiratory syndrome; WHO: World Health Organization; CDC: Centers for Disease Control and Prevention; OSCE: Objective structured clinical examination",2017 Jan 4,"['John, Amrita', 'Tomas, Myreen E.', 'Hari, Aditya', 'Wilson, Brigid M.', 'Donskey, Curtis J.']",Med Educ Online,,,True
1039a57c4d17c0c4eebcff505014cb5f11917cf1,PMC,Systematic review and meta-analysis for the use of ultrasound versus radiology in diagnosing of pneumonia,http://dx.doi.org/10.1186/s13089-017-0059-y,PMC5328906,28244009,CC BY,"BACKGROUND: Physicians are increasingly using point of care lung ultrasound (LUS) for diagnosing pneumonia, especially in critical situations as it represents relatively easy and immediately available tool. They also used it in many associated pathological conditions such as consolidation, pleural effusion, and interstitial syndrome with some reports of more accuracy than chest X-ray. This systematic review and meta-analysis are aimed to estimate the pooled diagnostic accuracy of ultrasound for the diagnosis of pneumonia versus the standard chest radiological imaging. METHODS AND MAIN RESULTS: A systematic literature search was conducted for all published studies comparing the diagnostic accuracy of LUS against a reference Chest radiological exam (C X-ray or Chest computed Tomography CT scan), combined with clinical criteria for pneumonia in all age groups. Eligible studies were required to have a Chest X-ray and/or CT scan at the time of clinical evaluation. The authors extracted qualitative and quantitative information from eligible studies, and calculated pooled sensitivity and specificity and pooled positive/negative likelihood ratios (LR). Twenty studies containing 2513 subjects were included in this meta-analysis. The pooled estimates for lung ultrasound in the diagnosis of pneumonia were, respectively, as follows: Overall pooled sensitivity and specificity for diagnosis of pneumonia by lung ultrasound were 0.85 (0.84–0.87) and 0.93 (0.92–0.95), respectively. Overall pooled positive and negative LRs were 11.05 (3.76–32.50) and 0.08 (0.04–0.15), pooled diagnostic Odds ratio was 173.64 (38.79–777.35), and area under the pooled ROC (AUC for SROC) was 0.978. CONCLUSION: Point of care lung ultrasound is an accurate tool for the diagnosis of pneumonia. Considering being easy, readily availability, low cost, and free from radiological hazards, it can be considered as important diagnostic strategy in this condition.",2017 Feb 27,"['Alzahrani, Saeed Ali', 'Al-Salamah, Majid Abdulatief', 'Al-Madani, Wedad Hussain', 'Elbarbary, Mahmoud A.']",Crit Ultrasound J,,,True
021af77daa9633d212e816cdbaf9f89240bfa3a0,PMC,MLKL Mediated Necroptosis Accelerates JEV-Induced Neuroinflammation in Mice,http://dx.doi.org/10.3389/fmicb.2017.00303,PMC5328978,28293227,CC BY,"Japanese encephalitis virus (JEV) is the most prevalent cause of viral encephalitis in Asia and the western Pacific. Neuronal death caused by JEV infection and inflammation induced cytotoxicity leads to progression and deterioration of Japanese encephalitis (JE). Mixed-lineage kinase domain-like protein (MLKL) mediated necroptosis is a newly discovered pathway of programmed cell death and participates in many inflammatory diseases. In this study, we demonstrated for the first time that necroptosis was involved in the neuronal loss during JE via immune-electron microscopy and immunochemistry. The expression of MLKL in neurons was upregulated in presence of JEV infection in vitro and in vivo. Deletion of MLKL alleviated the progression of JE and decreased the level of inflammatory cytokines in mice model. Taken together, this study provides evidence for the participation of necroptosis in the pathogenesis of JEV infection.",2017 Feb 28,"['Bian, Peiyu', 'Zheng, Xuyang', 'Wei, Li', 'Ye, Chuantao', 'Fan, Hong', 'Cai, Yanhui', 'Zhang, Ying', 'Zhang, Fanglin', 'Jia, Zhansheng', 'Lei, Yingfeng']",Front Microbiol,,,True
7ed1dcfad7266bfda122685c0009ec526f77909f,PMC,Interferon Lambda: Modulating Immunity in Infectious Diseases,http://dx.doi.org/10.3389/fimmu.2017.00119,PMC5328987,28293236,CC BY,"Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered. First, the IFNLR is not ubiquitously expressed: in particular, immune cells show significant variation in the expression levels of and susceptibilities to IFN-λs. Second, the binding affinities of individual IFN-λs to the IFNLR varies greatly and are generally lower compared to the binding affinities of IFN-α to its receptor. Finally, genetic variation in the form of a series of single-nucleotide polymorphisms (SNPs) linked to genes involved in the IFN-λ signaling cascade has been described and associated with the clinical course and treatment outcomes of hepatitis B and C virus infection. The clinical impact of IFN-λ signaling and the SNP variations may, however, reach far beyond viral hepatitis. Recent publications show important roles for IFN-λs in a broad range of viral infections such as human T-cell leukemia type-1 virus, rotaviruses, and influenza virus. IFN-λ also potentially modulates the course of bacterial colonization and infections as shown for Staphylococcus aureus and Mycobacterium tuberculosis. Although the immunological processes involved in controlling viral and bacterial infections are distinct, IFN-λs may interfere at various levels: as an innate immune cytokine with direct antiviral effects; or as a modulator of IFN-α-induced signaling via the suppressor of cytokine signaling 1 and the ubiquitin-specific peptidase 18 inhibitory feedback loops. In addition, the modulation of adaptive immune functions via macrophage and dendritic cell polarization, and subsequent priming, activation, and proliferation of pathogen-specific T- and B-cells may also be important elements associated with infectious disease outcomes. This review summarizes the emerging details of the IFN-λ immunobiology in the context of the host immune response and viral and bacterial infections.",2017 Feb 28,"['Syedbasha, Mohammedyaseen', 'Egli, Adrian']",Front Immunol,,,True
c4b7ab00946639c33eebee571e31d74e2543de95,PMC,Induction of Atypical Autophagy by Porcine Hemagglutinating Encephalomyelitis Virus Contributes to Viral Replication,http://dx.doi.org/10.3389/fcimb.2017.00056,PMC5328988,28293544,CC BY,"Autophagy is a basic biological metabolic process involving in intracellular membrane transport pathways that recycle cellular components and eliminate intracellular microorganisms within the lysosome. Autophagy also plays an important part in virus infection and propagation. However, some pathogens, including viruses, have evolved unique trick to escape or exploit autophagy. This study explores the mechanism of autophagy induction by porcine hemagglutinating encephalomyelitis virus (PHEV) in Neuro-2a cells, and examines the role of autophagy in PHEV replication. PHEV triggered autophagy in Neuro-2a cells is dependent on the presence of bulk double- or single-membrane vacuoles, the accumulation of GFP-LC3 fluorescent dots, and the LC3 lipidation. In addition, PHEV induced an incomplete autophagic effect because the degradation level of p62 did not change in PHEV-infected cells. Further validation was captured using LysoTracker and lysosome-associated membrane protein by indirect immunofluorescence labeling in PHEV-infected cells. We also investigated the change in viral replication by pharmacological experiments with the autophagy inducer rapamycin or the autophagy inhibitor 3-MA, and the lysosomal inhibitor chloroquine (CQ). Suppression of autophagy by 3-MA increased viral replication, compared with the mock treatment, while promoting of autophagy by rapamycin reduced PHEV replication. CQ treatment enhanced the LC3 lipidation in PHEV-infected Neuro-2a cells but lowered PHEV replication. These results show that PHEV infection induces atypical autophagy and causes the appearance of autophagosomes but blocks the fusion with lysosomes, which is necessary for the replication of PHEV in nerve cells.",2017 Feb 28,"['Ding, Ning', 'Zhao, Kui', 'Lan, Yungang', 'Li, Zi', 'Lv, Xiaoling', 'Su, Jingjing', 'Lu, Huijun', 'Gao, Feng', 'He, Wenqi']",Front Cell Infect Microbiol,,,True
671f1c2956296e84da394af512513ea165882eba,PMC,[Pyr(1)]Apelin-13((1–12)) Is a Biologically Active ACE2 Metabolite of the Endogenous Cardiovascular Peptide [Pyr(1)]Apelin-13,http://dx.doi.org/10.3389/fnins.2017.00092,PMC5329011,28293165,CC BY,"Aims: Apelin is a predicted substrate for ACE2, a novel therapeutic target. Our aim was to demonstrate the endogenous presence of the putative ACE2 product [Pyr(1)]apelin-13((1–12)) in human cardiovascular tissues and to confirm it retains significant biological activity for the apelin receptor in vitro and in vivo. The minimum active apelin fragment was also investigated. Methods and Results: [Pyr(1)]apelin-13 incubated with recombinant human ACE2 resulted in de novo generation of [Pyr(1)]apelin-13((1–12)) identified by mass spectrometry. Endogenous [Pyr(1)]apelin-13((1–12)) was detected by immunostaining in human heart and lung localized to the endothelium. Expression was undetectable in lung from patients with pulmonary arterial hypertension. In human heart [Pyr(1)]apelin-13((1–12)) (pK(i) = 8.04 ± 0.06) and apelin-13(F13A) (pK(i) = 8.07 ± 0.24) competed with [(125)I]apelin-13 binding with nanomolar affinity, 4-fold lower than for [Pyr(1)]apelin-13 (pK(i) = 8.83 ± 0.06) whereas apelin-17 exhibited highest affinity (pK(i) = 9.63 ± 0.17). The rank order of potency of peptides to inhibit forskolin-stimulated cAMP was apelin-17 (pD(2) = 10.31 ± 0.28) > [Pyr(1)]apelin-13 (pD(2) = 9.67 ± 0.04) ≥ apelin-13(F13A) (pD(2) = 9.54 ± 0.05) > [Pyr(1)]apelin-13((1–12)) (pD(2) = 9.30 ± 0.06). The truncated peptide apelin-13(R10M) retained nanomolar potency (pD(2) = 8.70 ± 0.04) but shorter fragments exhibited low micromolar potency. In a β-arrestin recruitment assay the rank order of potency was apelin-17 (pD(2) = 10.26 ± 0.09) >> [Pyr(1)]apelin-13 (pD(2) = 8.43 ± 0.08) > apelin-13(R10M) (pD(2) = 8.26 ± 0.17) > apelin-13(F13A) (pD(2) = 7.98 ± 0.04) ≥ [Pyr(1)]apelin-13((1–12)) (pD(2) = 7.84 ± 0.06) >> shorter fragments (pD(2) < 6). [Pyr(1)]apelin-13((1–12)) and apelin-13(F13A) contracted human saphenous vein with similar sub-nanomolar potencies and [Pyr(1)]apelin-13((1–12)) was a potent inotrope in paced mouse right ventricle and human atria. [Pyr(1)]apelin-13((1–12)) elicited a dose-dependent decrease in blood pressure in anesthetized rat and dose-dependent increase in forearm blood flow in human volunteers. Conclusions: We provide evidence that ACE2 cleaves [Pyr(1)]apelin-13 to [Pyr(1)]apelin-13((1–12)) and this cleavage product is expressed in human cardiovascular tissues. We have demonstrated biological activity of [Pyr(1)]apelin-13((1–12)) at the human and rodent apelin receptor in vitro and in vivo. Our data show that reported enhanced ACE2 activity in cardiovascular disease should not significantly compromise the beneficial effects of apelin based therapies for example in PAH.",2017 Feb 28,"['Yang, Peiran', 'Kuc, Rhoda E.', 'Brame, Aimée L.', 'Dyson, Alex', 'Singer, Mervyn', 'Glen, Robert C.', 'Cheriyan, Joseph', 'Wilkinson, Ian B.', 'Davenport, Anthony P.', 'Maguire, Janet J.']",Front Neurosci,,,True
de207527ab4b8826e6e8901d63e768c19691b178,PMC,Middle East respiratory syndrome coronavirus: review of the current situation in the world,http://dx.doi.org/10.1186/s40696-016-0019-2,PMC5329956,28265443,CC BY,"This article reviews the current epidemiology and clinical presentation of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection and describes the preparedness plan of several countries. The MERS-CoV was first reported in 2012 and has since infected more than 1600 patients in 26 countries, mostly in Saudi Arabia and the Middle East. The epidemiology of the infection is compatible with multiple introductions of the virus into humans from an animal reservoir, probably dromedary camels. The clinical presentation ranges from no symptoms to severe pneumonitis and respiratory failure. Most confirmed cases so far were part of MERS-CoV clusters in hospital settings, affecting mainly middle-aged men and patients with a chronic disease or immuno-suppressed status. There is no vaccine or anti-viral medication available. Viral epidemics can occur anywhere in today’s “global village”. MERS-CoV is a relatively new virus, and this work is intended to add to the still-sparse data on its epidemiology, modes of transmission, natural history, and clinical features as well as to describe the preparedness plan for MERS-CoV infection in several countries. Effective national and international preparedness plans are essential to predict and control outbreaks, improve patient management, and ensure global health security.",2016 May 4,"['Shapiro, Michael', 'London, Beny', 'Nigri, Daniel', 'Shoss, Alon', 'Zilber, Eyal', 'Fogel, Itay']",Disaster Mil Med,,,True
af59bab3c82817cf0ebe456cf3283a3d8217cabf,PMC,Syndromic surveillance in Vanuatu since Cyclone Pam: a descriptive study,http://dx.doi.org/10.5365/WPSAR.2016.7.3.009,PMC5330215,28246576,CC BY,"In 2012, Vanuatu designed and implemented a syndromic surveillance system based on the guidelines developed by the Pacific Community and the World Health Organization to provide early warning of outbreaks and other important public health events. Four core syndromes were endorsed for surveillance: acute fever and rash, prolonged fever, influenza-like illness and acute watery diarrhoea. In March 2015, Vanuatu was struck by Cyclone Pam, after which several important changes and improvements to the country’s syndromic surveillance were made. To date, there has been no formal evaluation of whether regular reports are occurring or that core syndromes are being documented. We therefore carried out a descriptive study in the 11 sentinel sites in Vanuatu conducting syndromic surveillance between July and December 2015. There was a total of 53 822 consultations which were higher in the first 13 weeks (n = 29 622) compared with the last 13 weeks (n = 24 200). During the six months, there were no cases of acute fever and rash or prolonged fever. There were cases with influenza-like illness from week 27 to 35, but no case was reported after week 35. Acute watery diarrhoea occurred in one or two cases per week during the whole study period. For these two core syndromes, there were generally more females than males, and about one third were children aged under 5 years. In conclusion, Vanuatu implemented changes to its new syndromic surveillance system from July to December 2015, although laboratory components had not yet been incorporated. The laboratory components are working in 2016 and will be the subject of a further report.",2011 Dec 19,"['Worwor, George', 'Harries, Anthony David', 'Merilles, Onofre Edwin', 'Viney, Kerri', 'Rory, Jean Jacques', 'Taleo, George', 'Guyant, Philippe']",Western Pac Surveill Response J,,,True
2264a7f6a968665b70a4a06c73e096e0710fc3f0,PMC,Impacts of allergic airway inflammation on lung pathology in a mouse model of influenza A virus infection,http://dx.doi.org/10.1371/journal.pone.0173008,PMC5330494,28245238,CC BY,"Influenza A virus is the respiratory pathogen responsible for influenza. Infection by the 2009 pandemic influenza A (H1N1) virus caused severe lower airway inflammation and pneumonia. Asthma is a chronic inflammatory disorder of the airways that affects the entire brachial tree, and was one of the commonest underlying medical conditions among patients hospitalized with the 2009 pandemic influenza virus infection. Although respiratory virus infections are the major causes of asthma exacerbation, the mechanism by which influenza exacerbates asthma is poorly understood. Animal models of disease comorbidity are crucial to understanding host-pathogen interactions and elucidating complex pathologies. Existing murine models of influenza virus infection in asthmatics show that asthmatic mice are highly resistant to influenza virus infection, which contradicts clinical observations in humans. Here, we developed a murine model of influenza virus/asthma comorbidity using NC/Nga mice, which are highly sensitive to allergic reactions such as atopic dermatitis and allergic airway inflammation. This model was then used to examine the impact of allergic airway inflammation on lung pathology in the 2009 pandemic influenza virus infected mice. The results showed that induction of acute allergic airway inflammation in pre-existing influenza virus infection had additive effects on exacerbation of lung pathology, which mirrors findings in human epidemiological studies. In contrast, pre-existing allergic airway inflammation protected from subsequent influenza virus infection, which was compatible with those of previous murine models of influenza virus infection in asthmatic mice. These variable outcomes of this murine model indicate that the temporal relation between allergic airway inflammation and influenza virus infection might play a critical role in asthma and influenza comorbidity. Thus, this murine model will further our understanding of how influenza virus infection affects an asthmatic host and may aid the development of strategies to improve treatments and outcomes for asthmatics harboring influenza virus infection.",2017 Feb 28,"['Kawaguchi, Akira', 'Suzuki, Tadaki', 'Ohara, Yuki', 'Takahashi, Kenta', 'Sato, Yuko', 'Ainai, Akira', 'Nagata, Noriyo', 'Tashiro, Masato', 'Hasegawa, Hideki']",PLoS One,,,True
14723bfc42908c3f8f522692be41062a7cda62d4,PMC,miR-21a-5p Contributes to Porcine Hemagglutinating Encephalomyelitis Virus Proliferation via Targeting CASK-Interactive Protein1 In vivo and vitro,http://dx.doi.org/10.3389/fmicb.2017.00304,PMC5331037,28298907,CC BY,"Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurovirulent coronavirus that can cause nervous symptoms in piglets with muscle tremors, hind limb paralysis, and nystagmus. Whether some factors affect virus replication and proliferation had not been fully understood in the course of nerve damage caused by PHEV infection. In recent years, some reports suggested that miRNA might play a key regulatory role in viral infection. In this study, we found the miR-21a-5p is notably up-regulated in the brains of mice and N2a cells infected with PHEV, and it down-regulated the expression of CASK-interactive protein1 (Caskin1) by directly targeting the 3′-UTR of Caskin1 using a Dual-Luciferase reporter assay. The over-expression of miR-21a-5p or Caskin1 knockdown in the host significantly contributes to PHEV proliferation. Conversely, the silencing of miR-21a-5p by miR-21a-5p inhibitors suppressed the virus proliferation. Taken together, our results indicate that Caskin1 is the direct target gene of miR-21a-5p, and it is advantageous to virus proliferation by down-regulating Caskin1. These findings may help in the development of strategies for therapeutic applications.",2017 Mar 1,"['Lv, Xiaoling', 'Zhao, Kui', 'Lan, Yungang', 'Li, Zi', 'Ding, Ning', 'Su, Jingjing', 'Lu, Huijun', 'Song, Deguang', 'Gao, Feng', 'He, Wenqi']",Front Microbiol,,,True
e6d560c0ed2c420b3ca34de569c8a46d3722e2da,PMC,Validation of the Arabic Version of the Early Childhood Oral Health Impact Scale (ECOHIS),http://dx.doi.org/10.1186/s12903-017-0353-x,PMC5331632,28245876,CC BY,"BACKGROUND: Assessment of the adverse effects of oral health problems on oral health-related quality of life (OHRQoL) is essential to ensure the well-being of children. The Early Childhood Oral Health Impact Scale (ECOHIS) is an instrument that was designed to assess caregivers’ perceptions of OHRQoL in preschool children. Although it has been translated into many languages, it has yet to be validated in Arabic. Therefore, this study aimed to translate this questionnaire to Arabic (A-ECOHIS) and test its psychometric properties. METHODS: Questionnaire responses from three samples of caregivers of preschool children ≤ 6 years of age were collected: (i) community-based (n = 422), from preschools selected as a stratified random sample; (ii) clinic-based, from those seeking pediatric dental care at a university clinic (n = 246); and (iii) a test-retest sample (n = 68), a clinic-based group of caregivers who completed questionnaires twice about siblings who were not receiving dental care. Children received a dental examination to assess their decayed, missed, filled teeth (dmft) scores. Convergent validity was evaluated by assessing the A-ECOHIS scores in relation to the response to a global question. Discriminant validity was evaluated by comparing the scores of children with varying levels of oral disease. Internal consistency was assessed by calculating Cronbach’s alpha, and the test-retest reliability was assessed using intra-class correlation coefficients (ICCs). RESULTS: The A-ECOHIS scores of the questionnaire sections and the global oral health rating were significantly correlated; Spearman correlation coefficients were, r = 0.55, P ≤ 0.01 (overall score), r = 0.54, P ≤ 0.01 (child section), and r = 0.51, P ≤ 0.01 (family section). The mean A-ECOHIS scores were also statistically significantly higher in children with higher dmft scores compared with lower dmft, and in the clinic-based sample compared with the community sample. The Cronbach’s alpha value of the the child, family sections and overall questionnaire were, 0.80, 0.78, and 0.85, respectively. The intra-class correlation coefficient (ICC) of A-ECOHIS was 0.86. CONCLUSION: The A-ECOHIS performed well on all psychometric tests to which it was applied. Thus, it is a valid and reliable instrument that can be used in Arabic-speaking caregivers of preschoolers aged 2 to 6 years.",2017 Feb 28,"['Farsi, Nada J.', 'El-Housseiny, Azza A.', 'Farsi, Deema J.', 'Farsi, Najat M.']",BMC Oral Health,,,True
765e023ee18436394fa56d1b2a388422e6201804,PMC,Protein Malnutrition Modifies Innate Immunity and Gene Expression by Intestinal Epithelial Cells and Human Rotavirus Infection in Neonatal Gnotobiotic Pigs,http://dx.doi.org/10.1128/mSphere.00046-17,PMC5332602,28261667,CC BY,"Malnutrition affects millions of children in developing countries, compromising immunity and contributing to increased rates of death from infectious diseases. Rotavirus is a major etiological agent of childhood diarrhea in developing countries, where malnutrition is prevalent. However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood. In this study, we used neonatal gnotobiotic (Gn) pigs transplanted with the fecal microbiota of a healthy 2-month-old infant (HIFM) and fed protein-deficient or -sufficient bovine milk diets. Protein deficiency induced hypoproteinemia, hypoalbuminemia, hypoglycemia, stunting, and generalized edema in Gn pigs, as observed in protein-malnourished children. Irrespective of the diet, human rotavirus (HRV) infection early, at HIFM posttransplantation day 3 (PTD3), resulted in adverse health effects and higher mortality rates (45 to 75%) than later HRV infection (PTD10). Protein malnutrition exacerbated HRV infection and affected the morphology and function of the small intestinal epithelial barrier. In pigs infected with HRV at PTD10, there was a uniform decrease in the function and/or frequencies of natural killer cells, plasmacytoid dendritic cells, and CD103(+) and apoptotic mononuclear cells and altered gene expression profiles of intestinal epithelial cells (chromogranin A, mucin 2, proliferating cell nuclear antigen, SRY-Box 9, and villin). Thus, we have established the first HIFM-transplanted neonatal pig model that recapitulates major aspects of protein malnutrition in children and can be used to evaluate physiologically relevant interventions. Our findings provide an explanation of why nutrient-rich diets alone may lack efficacy in malnourished children. IMPORTANCE Malnutrition and rotavirus infection, prevalent in developing countries, individually and in combination, affect the health of millions of children, compromising their immunity and increasing the rates of death from infectious diseases. However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood. We have established the first human infant microbiota-transplanted neonatal pig model of childhood malnutrition that reproduced the impaired immune, intestinal, and other physiological functions seen in malnourished children. This model can be used to evaluate relevant dietary and other health-promoting interventions. Our findings provide an explanation of why adequate nutrition alone may lack efficacy in malnourished children.",2017 Mar 1,"['Vlasova, Anastasia N.', 'Paim, Francine C.', 'Kandasamy, Sukumar', 'Alhamo, Moyasar A.', 'Fischer, David D.', 'Langel, Stephanie N.', 'Deblais, Loic', 'Kumar, Anand', 'Chepngeno, Juliet', 'Shao, Lulu', 'Huang, Huang-Chi', 'Candelero-Rueda, Rosario A.', 'Rajashekara, Gireesh', 'Saif, Linda J.']",mSphere,,,True
977a9e2664be64001c582cee1d83608e6af54c7d,PMC,Protein Malnutrition Modifies Innate Immunity and Gene Expression by Intestinal Epithelial Cells and Human Rotavirus Infection in Neonatal Gnotobiotic Pigs,http://dx.doi.org/10.1128/mSphere.00046-17,PMC5332602,28261667,CC BY,"Malnutrition affects millions of children in developing countries, compromising immunity and contributing to increased rates of death from infectious diseases. Rotavirus is a major etiological agent of childhood diarrhea in developing countries, where malnutrition is prevalent. However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood. In this study, we used neonatal gnotobiotic (Gn) pigs transplanted with the fecal microbiota of a healthy 2-month-old infant (HIFM) and fed protein-deficient or -sufficient bovine milk diets. Protein deficiency induced hypoproteinemia, hypoalbuminemia, hypoglycemia, stunting, and generalized edema in Gn pigs, as observed in protein-malnourished children. Irrespective of the diet, human rotavirus (HRV) infection early, at HIFM posttransplantation day 3 (PTD3), resulted in adverse health effects and higher mortality rates (45 to 75%) than later HRV infection (PTD10). Protein malnutrition exacerbated HRV infection and affected the morphology and function of the small intestinal epithelial barrier. In pigs infected with HRV at PTD10, there was a uniform decrease in the function and/or frequencies of natural killer cells, plasmacytoid dendritic cells, and CD103(+) and apoptotic mononuclear cells and altered gene expression profiles of intestinal epithelial cells (chromogranin A, mucin 2, proliferating cell nuclear antigen, SRY-Box 9, and villin). Thus, we have established the first HIFM-transplanted neonatal pig model that recapitulates major aspects of protein malnutrition in children and can be used to evaluate physiologically relevant interventions. Our findings provide an explanation of why nutrient-rich diets alone may lack efficacy in malnourished children. IMPORTANCE Malnutrition and rotavirus infection, prevalent in developing countries, individually and in combination, affect the health of millions of children, compromising their immunity and increasing the rates of death from infectious diseases. However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood. We have established the first human infant microbiota-transplanted neonatal pig model of childhood malnutrition that reproduced the impaired immune, intestinal, and other physiological functions seen in malnourished children. This model can be used to evaluate relevant dietary and other health-promoting interventions. Our findings provide an explanation of why adequate nutrition alone may lack efficacy in malnourished children.",2017 Mar 1,"['Vlasova, Anastasia N.', 'Paim, Francine C.', 'Kandasamy, Sukumar', 'Alhamo, Moyasar A.', 'Fischer, David D.', 'Langel, Stephanie N.', 'Deblais, Loic', 'Kumar, Anand', 'Chepngeno, Juliet', 'Shao, Lulu', 'Huang, Huang-Chi', 'Candelero-Rueda, Rosario A.', 'Rajashekara, Gireesh', 'Saif, Linda J.']",mSphere,,,False
026447f6e8f25d774926c5f38f8c8ae1f62aa54d,PMC,Bat Astroviruses: Towards Understanding the Transmission Dynamics of a Neglected Virus Family,http://dx.doi.org/10.3390/v9020034,PMC5332953,28230787,CC BY,"Bats belong to the order Chiroptera that represents the second largest order of mammals with more than 1200 species and an almost global distribution. Environmental changes and deforestation have severely influenced many ecosystems, intensifying the contact between wildlife and humans. In recent years, bats have been found to harbor a number of different viruses with zoonotic potential, as well as a great diversity of astroviruses, for which the question of zoonotic potential remains unanswered to date. Human astroviruses have been identified as the causative agent for diarrhea in children and immunocompromised patients. For a long time, astroviruses have been considered to be strictly species-specific. However, a great genetic diversity has recently been discovered among animal and human astroviruses that might indicate the potential of these viruses to cross species barriers. Furthermore, our knowledge about the tissue tropism of astroviruses has been expanded to some neurotropic strains that have recently been shown to be responsible for encephalitis in humans and livestock. This review gives an overview on what is known about astroviruses in bats, humans and livestock, especially bovines and pigs. Future research activities are suggested to unravel astrovirus infection dynamics in bat populations to further assess the zoonotic potential of these viruses.",2017 Feb 21,"['Fischer, Kerstin', 'Pinho dos Reis, Vinícius', 'Balkema-Buschmann, Anne']",Viruses,,,True
da5958b5a0d82961e2cef5f42fe1e3d9ce6a30cb,PMC,Advances in Non-Viral DNA Vectors for Gene Therapy,http://dx.doi.org/10.3390/genes8020065,PMC5333054,28208635,CC BY,"Uses of viral vectors have thus far eclipsed uses of non-viral vectors for gene therapy delivery in the clinic. Viral vectors, however, have certain issues involving genome integration, the inability to be delivered repeatedly, and possible host rejection. Fortunately, development of non-viral DNA vectors has progressed steadily, especially in plasmid vector length reduction, now allowing these tools to fill in specifically where viral or other non-viral vectors may not be the best options. In this review, we examine the improvements made to non-viral DNA gene therapy vectors, highlight opportunities for their further development, address therapeutic needs for which their use is the logical choice, and discuss their future expansion into the clinic.",2017 Feb 10,"['Hardee, Cinnamon L.', 'Arévalo-Soliz, Lirio Milenka', 'Hornstein, Benjamin D.', 'Zechiedrich, Lynn']",Genes (Basel),,,True
7a6e0d1d7e1a31f6107a62a0030818b766a00dd8,PMC,"Comparison of Influenza Epidemiological and Virological Characteristics between Outpatients and Inpatients in Zhejiang Province, China, March 2011–June 2015",http://dx.doi.org/10.3390/ijerph14020217,PMC5334771,28241447,CC BY,"Given the rapid rate of global spread and consequently healthcare costs related to influenza, surveillance plays an important role in monitoring the emerging pandemics in China. However, the characteristics of influenza in Southeast of China haven’t been fully studied. Our study use the surveillance data collected from 16 sentinel hospitals across Zhejiang Province during March 2011 through June 2015, including the demographic information and respiratory specimens from influenza-like illness (ILI) patients and severe acute respiratory illness (SARI) patients. As analysis results, most SARI and ILI patients were in the age group of 0–4 years old (62.38% of ILI and 71.54% of SARI). The respiratory specimens have statistically significantly higher positive rate for influenza among ILI patients than that among SARI patients (p < 0.001). The comparison between ILI patients and SARI patients shows no statistically significantly difference in detecting influenza virus type and influenza A virus subtype. The SARI and ILI patients were found to be positively correlated for overall positive rate (r = 0.63, p < 0.001), the weekly percentage of A(H1N1)pdm09 (r = 0.51, p < 0.001), influenza B virus (r = 0.17, p = 0.013), and A/H3N2 (r = 0.43, p < 0.001) among all the positive numbers. Our study demonstrated that the activities of influenza virus, including its subtypes, had a similar temporal pattern between ILI and SARI cases.",2017 Feb 22,"['Cheng, Wei', 'Yu, Zhao', 'Liu, Shelan', 'Zhang, Xueying', 'Wang, Xiaoxiao', 'Cai, Jian', 'Ling, Feng', 'Chen, Enfu']",Int J Environ Res Public Health,,,True
a81f08700b297b78c8f255c4a428f2675ca45ef9,PMC,The Rotavirus NSP4 Viroporin Domain is a Calcium-conducting Ion Channel,http://dx.doi.org/10.1038/srep43487,PMC5335360,28256607,CC BY,"Viroporins are small virus-encoded ion channel proteins. Most viroporins are monovalent selective cation channels, with few showing the ability to conduct divalent cations, like calcium (Ca(2+)). Nevertheless, some viroporins are known to disrupt host cell Ca(2+) homeostasis, which is critical for virus replication and pathogenesis. Rotavirus nonstructural protein 4 (NSP4) is an endoplasmic reticulum transmembrane glycoprotein that has a viroporin domain (VPD), and NSP4 viroporin activity elevates cytosolic Ca(2+) in mammalian cells. The goal of this study was to demonstrate that the NSP4 VPD forms an ion channel and determine whether the channel can conduct Ca(2+). Using planar lipid bilayer and liposome patch clamp electrophysiology, we show that a synthetic peptide of the NSP4 VPD has ion channel activity. The NSP4 VPD was selective for cations over anions and channel activity was observed to have both well-defined “square top” openings as well as fast current fluctuations, similar to other viroporins. Importantly, the NSP4 VPD showed similar conductance of divalent cations (Ca(2+) and Ba(2+)) as monovalent cations (K(+)), but a viroporin defective mutant lacked Ca(2+) conductivity. These data demonstrate that the NSP4 VPD is a Ca(2+)-conducting viroporin and establish the mechanism by which NSP4 disturbs host cell Ca(2+) homeostasis.",2017 Mar 3,"['Pham, Thieng', 'Perry, Jacob L.', 'Dosey, Timothy L.', 'Delcour, Anne H.', 'Hyser, Joseph M.']",Sci Rep,,,True
1d34f06b4b343c893f1f94acbd1583ec41b86142,PMC,The Rotavirus NSP4 Viroporin Domain is a Calcium-conducting Ion Channel,http://dx.doi.org/10.1038/srep43487,PMC5335360,28256607,CC BY,"Viroporins are small virus-encoded ion channel proteins. Most viroporins are monovalent selective cation channels, with few showing the ability to conduct divalent cations, like calcium (Ca(2+)). Nevertheless, some viroporins are known to disrupt host cell Ca(2+) homeostasis, which is critical for virus replication and pathogenesis. Rotavirus nonstructural protein 4 (NSP4) is an endoplasmic reticulum transmembrane glycoprotein that has a viroporin domain (VPD), and NSP4 viroporin activity elevates cytosolic Ca(2+) in mammalian cells. The goal of this study was to demonstrate that the NSP4 VPD forms an ion channel and determine whether the channel can conduct Ca(2+). Using planar lipid bilayer and liposome patch clamp electrophysiology, we show that a synthetic peptide of the NSP4 VPD has ion channel activity. The NSP4 VPD was selective for cations over anions and channel activity was observed to have both well-defined “square top” openings as well as fast current fluctuations, similar to other viroporins. Importantly, the NSP4 VPD showed similar conductance of divalent cations (Ca(2+) and Ba(2+)) as monovalent cations (K(+)), but a viroporin defective mutant lacked Ca(2+) conductivity. These data demonstrate that the NSP4 VPD is a Ca(2+)-conducting viroporin and establish the mechanism by which NSP4 disturbs host cell Ca(2+) homeostasis.",2017 Mar 3,"['Pham, Thieng', 'Perry, Jacob L.', 'Dosey, Timothy L.', 'Delcour, Anne H.', 'Hyser, Joseph M.']",Sci Rep,,,False
c16d19032f42486b997727ee0f732ab9fd5b9a84,PMC,Rhesus macaque IFITM3 gene polymorphisms and SIV infection,http://dx.doi.org/10.1371/journal.pone.0172847,PMC5336200,28257482,CC BY,"Interferon-induced transmembrane proteins (IFITMs) have been recognized as important antiviral effectors of the innate immune system, both in cell culture and in infected humans. In particular, polymorphisms of the human IFITM3 gene have been shown to affect disease severity and progression in influenza A virus (FLUAV) and human immunodeficiency virus (HIV) infection, respectively. Rhesus macaques (Macaca mulatta) are commonly used to model human infections and the experimental inoculation of these animals with simian immunodeficiency virus (SIV) is one of the best models for HIV/AIDS in humans. However, information on the role of IFITM3 in SIV infection of rhesus macaques is currently lacking. We show that rhesus macaque (rh) IFITM3 inhibits SIV and FLUAV entry in cell culture, although with moderately reduced efficiency as compared to its human counterpart. We further report the identification of 16 polymorphisms in the rhIFITM3 gene, three of which were exonic and synonymous while the remainder was located in non-coding regions. Employing previously characterized samples from two cohorts of SIV-infected rhesus macaques, we investigated the relationship between these rhIFITM3 polymorphisms and both AIDS-free survival time and virus load. In cohort 1, several intronic polymorphisms were significantly associated with virus load or survival. However, an association with both parameters was not observed and significance was lost in most cases when animals were stratified for the presence of MHC allele Mamu-A1*001. Moreover, no significant genotype-phenotype associations were detected in cohort 2. These results suggest that, although IFITM3 can inhibit SIV infection in cell culture, genetic variation in rhIFITM3 might have only a minor impact on the course of SIV infection in experimentally infected animals.",2017 Mar 3,"['Winkler, Michael', 'Gärtner, Sabine', 'Wrensch, Florian', 'Krawczak, Michael', 'Sauermann, Ulrike', 'Pöhlmann, Stefan']",PLoS One,,,True
a8e457ae28d8267ce76183b65b7ff026c346bec5,PMC,The Contribution of Ageing to Hospitalisation Days in Hong Kong: A Decomposition Analysis,http://dx.doi.org/10.15171/ijhpm.2016.108,PMC5337253,28812795,CC BY,"Background: Ageing has become a serious challenge in Hong Kong and globally. It has serious implications for health expenditure, which accounts for nearly 20% of overall government expenditure. Here we assess the contribution of ageing and related factors to hospitalisation days in Hong Kong. We used hospital discharge data from all publicly funded hospitals in Hong Kong between 2001 and 2012. Methods: A decomposition method was used to examine the factors that account for the change of total hospitalisation days during the two periods, 2001-2004 and 2004-2012. The five factors include two demographic factors – population size and age-gender composition – and three service components – hospital discharge rate, number of discharge episodes per patient, and average length of stay (LOS) – which are all measured at age-gender group level. In order to assess the health cost burden in the future, we also project the total hospitalisation days up to 2041, for a range of scenarios. Results: During the decreasing period of hospitalisation days (2001-2004), the reduction of LOS contributed to about 60% of the reduction. For the period of increase (2004-2012), ageing is associated with an increase in total hospitalisation days of 1.03 million, followed by an increase in hospital discharge rates (0.67 million), an increase in the number of discharge episodes per patient (0.62 million), and population growth (0.43 million). The reduction of LOS has greatly offset these increases (-2.19 million days), and has become one of the most significant factors in containing the increasing number of hospitalisation days. Projected increases in total hospitalisation days under different scenarios have highlighted that the contribution of ageing will become even more prominent after 2022. Conclusion: Hong Kong is facing increasing healthcare burden caused by the rapid increase in demand for inpatient services due to ageing. Better management of inpatient services with the aim of increasing efficiency and reducing LOS, avoidable hospitalisation and readmission, without compromising patient satisfaction and quality of service, are crucial for containing the rapid and enormous increases in total hospitalisation days for Hong Kong. The results would be relevant to many rapidly ageing societies in this region.",2016 Aug 17,"['Kwok, Chi Leung', 'Lee, Carmen KM', 'Lo, William TL', 'Yip, Paul SF']",Int J Health Policy Manag,,,True
4d1c9efa716ac08a4527a14023fc714ef4e3d8ae,PMC,A Rare Cause of Childhood Cerebellitis-Influenza Infection: A Case Report and Systematic Review of Literature,http://dx.doi.org/10.1155/2017/4039358,PMC5337386,28299224,CC BY,"Acute cerebellitis is a benign neurologic condition generally caused by viral or bacterial infections. Influenza associated cerebellitis is extremely rare; a 6-year-old boy with acute cerebellitis, who presented with fever, vomiting, weakness, febrile seizure, and acute cerebellar features, is discussed in this article.",2017 Feb 20,"['Gökçe, Şule', 'Kurugol, Zafer', 'Aslan, Aslı']",Case Rep Pediatr,,,True
d3622e7ade6a1af92f1f239619932a3863c77e19,PMC,IL-10: A Multifunctional Cytokine in Viral Infections,http://dx.doi.org/10.1155/2017/6104054,PMC5337865,28316998,CC BY,"The anti-inflammatory master regulator IL-10 is critical to protect the host from tissue damage during acute phases of immune responses. This regulatory mechanism, central to T cell homeostasis, can be hijacked by viruses to evade immunity. IL-10 can be produced by virtually all immune cells, and it can also modulate the function of these cells. Understanding the effects of this multifunctional cytokine is therefore a complex task. In the present review we discuss the factors driving IL-10 production and the cellular sources of the cytokine during antiviral immune responses. We particularly focus on the IL-10 regulatory mechanisms that impact antiviral immune responses and how viruses can use this central regulatory pathway to evade immunity and establish chronic/latent infections.",2017 Feb 20,"['Rojas, José M.', 'Avia, Miguel', 'Martín, Verónica', 'Sevilla, Noemí']",J Immunol Res,,,True
bede1530aa4f5b0fdc57cd2d582bc7e4f153c1e6,PMC,Network theory may explain the vulnerability of medieval human settlements to the Black Death pandemic,http://dx.doi.org/10.1038/srep43467,PMC5338018,28262733,CC BY,"Epidemics can spread across large regions becoming pandemics by flowing along transportation and social networks. Two network attributes, transitivity (when a node is connected to two other nodes that are also directly connected between them) and centrality (the number and intensity of connections with the other nodes in the network), are widely associated with the dynamics of transmission of pathogens. Here we investigate how network centrality and transitivity influence vulnerability to diseases of human populations by examining one of the most devastating pandemic in human history, the fourteenth century plague pandemic called Black Death. We found that, after controlling for the city spatial location and the disease arrival time, cities with higher values of both centrality and transitivity were more severely affected by the plague. A simulation study indicates that this association was due to central cities with high transitivity undergo more exogenous re-infections. Our study provides an easy method to identify hotspots in epidemic networks. Focusing our effort in those vulnerable nodes may save time and resources by improving our ability of controlling deadly epidemics.",2017 Mar 6,"['Gómez, José M.', 'Verdú, Miguel']",Sci Rep,,,True
24708179db3a64c831215a30805bf37e6d27ccf7,PMC,Network theory may explain the vulnerability of medieval human settlements to the Black Death pandemic,http://dx.doi.org/10.1038/srep43467,PMC5338018,28262733,CC BY,"Epidemics can spread across large regions becoming pandemics by flowing along transportation and social networks. Two network attributes, transitivity (when a node is connected to two other nodes that are also directly connected between them) and centrality (the number and intensity of connections with the other nodes in the network), are widely associated with the dynamics of transmission of pathogens. Here we investigate how network centrality and transitivity influence vulnerability to diseases of human populations by examining one of the most devastating pandemic in human history, the fourteenth century plague pandemic called Black Death. We found that, after controlling for the city spatial location and the disease arrival time, cities with higher values of both centrality and transitivity were more severely affected by the plague. A simulation study indicates that this association was due to central cities with high transitivity undergo more exogenous re-infections. Our study provides an easy method to identify hotspots in epidemic networks. Focusing our effort in those vulnerable nodes may save time and resources by improving our ability of controlling deadly epidemics.",2017 Mar 6,"['Gómez, José M.', 'Verdú, Miguel']",Sci Rep,,,True
9dd6e3df008179b4c54ac823f76192a8a174b62d,PMC,"GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses",http://dx.doi.org/10.1038/srep43395,PMC5338263,28262699,CC BY,"GS-5734 is a monophosphate prodrug of an adenosine nucleoside analog that showed therapeutic efficacy in a non-human primate model of Ebola virus infection. It has been administered under compassionate use to two Ebola patients, both of whom survived, and is currently in Phase 2 clinical development for treatment of Ebola virus disease. Here we report the antiviral activities of GS-5734 and the parent nucleoside analog across multiple virus families, providing evidence to support new indications for this compound against human viruses of significant public health concern.",2017 Mar 6,"['Lo, Michael K.', 'Jordan, Robert', 'Arvey, Aaron', 'Sudhamsu, Jawahar', 'Shrivastava-Ranjan, Punya', 'Hotard, Anne L.', 'Flint, Mike', 'McMullan, Laura K.', 'Siegel, Dustin', 'Clarke, Michael O.', 'Mackman, Richard L.', 'Hui, Hon C.', 'Perron, Michel', 'Ray, Adrian S.', 'Cihlar, Tomas', 'Nichol, Stuart T.', 'Spiropoulou, Christina F.']",Sci Rep,,,True
fba9ec3bc7b78afefc40da07c8d560ab920f50eb,PMC,"GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses",http://dx.doi.org/10.1038/srep43395,PMC5338263,28262699,CC BY,"GS-5734 is a monophosphate prodrug of an adenosine nucleoside analog that showed therapeutic efficacy in a non-human primate model of Ebola virus infection. It has been administered under compassionate use to two Ebola patients, both of whom survived, and is currently in Phase 2 clinical development for treatment of Ebola virus disease. Here we report the antiviral activities of GS-5734 and the parent nucleoside analog across multiple virus families, providing evidence to support new indications for this compound against human viruses of significant public health concern.",2017 Mar 6,"['Lo, Michael K.', 'Jordan, Robert', 'Arvey, Aaron', 'Sudhamsu, Jawahar', 'Shrivastava-Ranjan, Punya', 'Hotard, Anne L.', 'Flint, Mike', 'McMullan, Laura K.', 'Siegel, Dustin', 'Clarke, Michael O.', 'Mackman, Richard L.', 'Hui, Hon C.', 'Perron, Michel', 'Ray, Adrian S.', 'Cihlar, Tomas', 'Nichol, Stuart T.', 'Spiropoulou, Christina F.']",Sci Rep,,,False
2786687808083b1a23083be32dae8229ff545179,PMC,Intraperitoneal adoptive transfer of mesenchymal stem cells enhances recovery from acid aspiration acute lung injury in mice,http://dx.doi.org/10.1186/s40635-017-0126-5,PMC5339261,28265979,CC BY,"BACKGROUND: Mesenchymal stem cells (MSCs) might act as fine-tuners of inflammation during acute lung injury. We assessed the effects of adoptive transfer of MSCs in acid aspiration acute lung injury and explored the role of long pentraxin PTX3. METHODS: We conducted a prospective experimental interventional study on wild-type (WT) and PTX3-deficient (PTX3(−/−)) mice. Acute lung injury was induced in WT and PTX3(−/−) mice by instillation of hydrochloric acid into the right bronchus. One hour later, animals received intraperitoneal sterile phosphate-buffered saline (PBS), WT-MSCs (1 × 10(6)) or PTX3(−/−)-MSCs (1 × 10(6)). Twenty-four hours after injury, we measured the effects of treatments on arterial blood gases, wet/dry lung weight (W/D), CT scan analysis of lung collapse, neutrophils, TNFα and CXCL1 in bronchoalveolar lavage, and plasma PTX3. d-dimer was assayed in 1 week and OH-proline in 2 weeks to track the fibrotic evolution. RESULTS: In 24 h, in comparison to PBS, WT-MSCs improved oxygenation and reduced W/D and alveolar collapse. These effects were associated with decreased concentrations of alveolar neutrophils and cytokines. WT-MSCs increased d-dimer concentration and decreased OH-proline levels, too. Treatment with PTX3(−/−)-MSCs ameliorated oxygenation, W/D, and alveolar TNFα, though to a lesser extent than WT-MSCs. PTX3(−/−)-MSCs did not improve lung collapse, neutrophil count, CXCL1, d-dimer, and OH-proline concentrations. The protective effects of WT-MSCs were dampened by lack of endogenous PTX3, too. CONCLUSIONS: In acid aspiration acute lung injury, MSCs improve pulmonary function and limit fibrosis by fine-tuning inflammation. The role of PTX3 in determining MSCs’ effects might merit further scrutiny. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40635-017-0126-5) contains supplementary material, which is available to authorized users.",2017 Mar 6,"['Mauri, Tommaso', 'Zambelli, Vanessa', 'Cappuzzello, Claudia', 'Bellani, Giacomo', 'Dander, Erica', 'Sironi, Marina', 'Castiglioni, Vittoria', 'Doni, Andrea', 'Mantovani, Alberto', 'Biondi, Andrea', 'Garlanda, Cecilia', 'D’amico, Giovanna', 'Pesenti, Antonio']",Intensive Care Med Exp,,,True
5fb0184e30b9a7107983d9316b1c925508b75834,PMC,Microbial Neuraminidase Induces a Moderate and Transient Myelin Vacuolation Independent of Complement System Activation,http://dx.doi.org/10.3389/fneur.2017.00078,PMC5339270,28326060,CC BY,"AIMS: Some central nervous system pathogens express neuraminidase (NA) on their surfaces. In the rat brain, a single intracerebroventricular (ICV) injection of NA induces myelin vacuolation in axonal tracts. Here, we explore the nature, the time course, and the role of the complement system in this damage. METHODS: The spatiotemporal analysis of myelin vacuolation was performed by optical and electron microscopy. Myelin basic protein-positive area and oligodendrocyte transcription factor (Olig2)-positive cells were quantified in the damaged bundles. Neuronal death in the affected axonal tracts was assessed by Fluoro-Jade B and anti-caspase-3 staining. To evaluate the role of the complement, membrane attack complex (MAC) deposition on damaged bundles was analyzed using anti-C5b9. Rats ICV injected with the anaphylatoxin C5a were studied for myelin damage. In addition, NA-induced vacuolation was studied in rats with different degrees of complement inhibition: normal rats treated with anti-C5-blocking antibody and C6-deficient rats. RESULTS: The stria medullaris, the optic chiasm, and the fimbria were the most consistently damaged axonal tracts. Vacuolation peaked 7 days after NA injection and reverted by day 15. Olig2+ cell number in the damaged tracts was unaltered, and neurodegeneration associated with myelin alterations was not detected. MAC was absent on damaged axonal tracts, as revealed by C5b9 immunostaining. Rats ICV injected with the anaphylatoxin C5a displayed no myelin injury. When the complement system was experimentally or constitutively inhibited, NA-induced myelin vacuolation was similar to that observed in normal rats. CONCLUSION: Microbial NA induces a moderate and transient myelin vacuolation that is not caused either by neuroinflammation or complement system activation.",2017 Mar 7,"['Granados-Durán, Pablo', 'López-Ávalos, María Dolores', 'Cifuentes, Manuel', 'Pérez-Martín, Margarita', 'Fernández-Arjona, María del Mar', 'Hughes, Timothy R.', 'Johnson, Krista', 'Morgan, B. Paul', 'Fernández-Llebrez, Pedro', 'Grondona, Jesús M.']",Front Neurol,,,True
7e232c192b439ef6a844be6a2f40bbbae64469fb,PMC,Targeted antigen delivery to dendritic cells elicits robust antiviral T cell-mediated immunity in the liver,http://dx.doi.org/10.1038/srep43985,PMC5339819,28266658,CC BY,"Hepatotropic viruses such as hepatitis C virus cause life-threatening chronic liver infections in millions of people worldwide. Targeted in vivo antigen-delivery to cross-presenting dendritic cells (DCs) has proven to be extraordinarily efficient in stimulating antigen-specific T cell responses. To determine whether this approach would as well be suitable to induce local antiviral effector T cells in the liver we compared different vaccine formulations based on either the targeting of DEC-205 or TLR2/6 on cross-presenting DCs or formulations not involving in vivo DC targeting. As read-outs we used in vivo hepatotropic adenovirus challenge, histology and automated multidimensional fluorescence microscopy (MELC). We show that targeted in vivo antigen delivery to cross-presenting DCs is highly effective in inducing antiviral CTLs capable of eliminating virus-infected hepatocytes, while control vaccine formulation not involving DC targeting failed to induce immunity against hepatotropic virus. Moreover, we observed distinct patterns of CD8(+) T cell interaction with virus-infected and apoptotic hepatocytes in the two DC-targeting groups suggesting that the different vaccine formulations may stimulate distinct types of effector functions. Our findings represent an important step toward the future development of vaccines against hepatotropic viruses and the treatment of patients with hepatic virus infection after liver transplantation to avoid reinfection.",2017 Mar 7,"['Volckmar, Julia', 'Gereke, Marcus', 'Ebensen, Thomas', 'Riese, Peggy', 'Philipsen, Lars', 'Lienenklaus, Stefan', 'Wohlleber, Dirk', 'Klopfleisch, Robert', 'Stegemann-Koniszewski, Sabine', 'Müller, Andreas J.', 'Gruber, Achim D.', 'Knolle, Percy', 'Guzman, Carlos A.', 'Bruder, Dunja']",Sci Rep,,,True
5b1ff90bfb94f984a838fe6f3a806cdedc3aa182,PMC,Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development,http://dx.doi.org/10.3389/fimmu.2017.00239,PMC5340775,28337198,CC BY,"Subunit vaccines are safer but less immunogenic than live-attenuated vaccines or whole cell inactivated vaccines. Adjuvants are used to enhance and modulate antigen (Ag) immunogenicity, aiming to induce a protective and long-lasting immune response. Several molecules and formulations have been studied for their adjuvanticity, but only seven have been approved to formulate human vaccines. Metallic nanoparticles (MeNPs), particularly those containing gold and iron oxides, are widely used in medicine for diagnosis and therapy and have been used as carriers for drugs and vaccines. However, little is known about the immune response elicited by MeNPs or about their importance in the development of new vaccines. There is evidence that these particles display adjuvant characteristics, promoting cell recruitment, antigen-presenting cell activation, cytokine production, and inducing a humoral immune response. This review focuses on the characteristics of MeNPs that could facilitate the induction of a cellular immune response, particularly T-helper 1 and T-helper 17, and their potential functions as adjuvants for subunit vaccines.",2017 Mar 8,"['Marques Neto, Lázaro Moreira', 'Kipnis, André', 'Junqueira-Kipnis, Ana Paula']",Front Immunol,,,True
99f6ca41bcf6a11e4a3c722d5e00a9bfec79ca19,PMC,A Reverse Genetics Platform That Spans the Zika Virus Family Tree,http://dx.doi.org/10.1128/mBio.02014-16,PMC5340872,28270583,CC BY,"Zika virus (ZIKV), a mosquito-borne flavivirus discovered in 1947, has only recently caused large outbreaks and emerged as a significant human pathogen. In 2015, ZIKV was detected in Brazil, and the resulting epidemic has spread throughout the Western Hemisphere. Severe complications from ZIKV infection include neurological disorders such as Guillain-Barré syndrome in adults and a variety of fetal abnormalities, including microcephaly, blindness, placental insufficiency, and fetal demise. There is an urgent need for tools and reagents to study the pathogenesis of epidemic ZIKV and for testing vaccines and antivirals. Using a reverse genetics platform, we generated six ZIKV infectious clones and derivative viruses representing diverse temporal and geographic origins. These include three versions of MR766, the prototype 1947 strain (with and without a glycosylation site in the envelope protein), and H/PF/2013, a 2013 human isolate from French Polynesia representative of the virus introduced to Brazil. In the course of synthesizing a clone of a circulating Brazilian strain, phylogenetic studies identified two distinct ZIKV clades in Brazil. We reconstructed viable clones of strains SPH2015 and BeH819015, representing ancestral members of each clade. We assessed recombinant virus replication, binding to monoclonal antibodies, and virulence in mice. This panel of molecular clones and recombinant virus isolates will enable targeted studies of viral determinants of pathogenesis, adaptation, and evolution, as well as the rational attenuation of contemporary outbreak strains to facilitate the design of vaccines and therapeutics.",2017 Mar 7,"['Widman, Douglas G.', 'Young, Ellen', 'Yount, Boyd L.', 'Plante, Kenneth S.', 'Gallichotte, Emily N.', 'Carbaugh, Derek L.', 'Peck, Kayla M.', 'Plante, Jessica', 'Swanstrom, Jesica', 'Heise, Mark T.', 'Lazear, Helen M.', 'Baric, Ralph S.']",mBio,,,True
47826d4f9693f8859eff729ef432cc24d41cd896,PMC,Technologies for Proteome-Wide Discovery of Extracellular Host-Pathogen Interactions,http://dx.doi.org/10.1155/2017/2197615,PMC5340944,28321417,CC BY,"Pathogens have evolved unique mechanisms to breach the cell surface barrier and manipulate the host immune response to establish a productive infection. Proteins exposed to the extracellular environment, both cell surface-expressed receptors and secreted proteins, are essential targets for initial invasion and play key roles in pathogen recognition and subsequent immunoregulatory processes. The identification of the host and pathogen extracellular molecules and their interaction networks is fundamental to understanding tissue tropism and pathogenesis and to inform the development of therapeutic strategies. Nevertheless, the characterization of the proteins that function in the host-pathogen interface has been challenging, largely due to the technical challenges associated with detection of extracellular protein interactions. This review discusses available technologies for the high throughput study of extracellular protein interactions between pathogens and their hosts, with a focus on mammalian viruses and bacteria. Emerging work illustrates a rich landscape for extracellular host-pathogen interaction and points towards the evolution of multifunctional pathogen-encoded proteins. Further development and application of technologies for genome-wide identification of extracellular protein interactions will be important in deciphering functional host-pathogen interaction networks, laying the foundation for development of novel therapeutics.",2017 Feb 22,"Martinez-Martin, Nadia",J Immunol Res,,,True
f78f42cdcf23e60059e6ef785c1d72072824832a,PMC,Ultrastructural Characterization of Zika Virus Replication Factories,http://dx.doi.org/10.1016/j.celrep.2017.02.014,PMC5340982,28249158,CC BY,"A global concern has emerged with the pandemic spread of Zika virus (ZIKV) infections that can cause severe neurological symptoms in adults and newborns. ZIKV is a positive-strand RNA virus replicating in virus-induced membranous replication factories (RFs). Here we used various imaging techniques to investigate the ultrastructural details of ZIKV RFs and their relationship with host cell organelles. Analyses of human hepatic cells and neural progenitor cells infected with ZIKV revealed endoplasmic reticulum (ER) membrane invaginations containing pore-like openings toward the cytosol, reminiscent to RFs in Dengue virus-infected cells. Both the MR766 African strain and the H/PF/2013 Asian strain, the latter linked to neurological diseases, induce RFs of similar architecture. Importantly, ZIKV infection causes a drastic reorganization of microtubules and intermediate filaments forming cage-like structures surrounding the viral RF. Consistently, ZIKV replication is suppressed by cytoskeleton-targeting drugs. Thus, ZIKV RFs are tightly linked to rearrangements of the host cell cytoskeleton.",2017 Feb 28,"['Cortese, Mirko', 'Goellner, Sarah', 'Acosta, Eliana Gisela', 'Neufeldt, Christopher John', 'Oleksiuk, Olga', 'Lampe, Marko', 'Haselmann, Uta', 'Funaya, Charlotta', 'Schieber, Nicole', 'Ronchi, Paolo', 'Schorb, Martin', 'Pruunsild, Priit', 'Schwab, Yannick', 'Chatel-Chaix, Laurent', 'Ruggieri, Alessia', 'Bartenschlager, Ralf']",Cell Rep,,,False
daff41630d6cdd363db1971c2a7ebb0414c58a96,PMC,Ultrastructural Characterization of Zika Virus Replication Factories,http://dx.doi.org/10.1016/j.celrep.2017.02.014,PMC5340982,28249158,CC BY,"A global concern has emerged with the pandemic spread of Zika virus (ZIKV) infections that can cause severe neurological symptoms in adults and newborns. ZIKV is a positive-strand RNA virus replicating in virus-induced membranous replication factories (RFs). Here we used various imaging techniques to investigate the ultrastructural details of ZIKV RFs and their relationship with host cell organelles. Analyses of human hepatic cells and neural progenitor cells infected with ZIKV revealed endoplasmic reticulum (ER) membrane invaginations containing pore-like openings toward the cytosol, reminiscent to RFs in Dengue virus-infected cells. Both the MR766 African strain and the H/PF/2013 Asian strain, the latter linked to neurological diseases, induce RFs of similar architecture. Importantly, ZIKV infection causes a drastic reorganization of microtubules and intermediate filaments forming cage-like structures surrounding the viral RF. Consistently, ZIKV replication is suppressed by cytoskeleton-targeting drugs. Thus, ZIKV RFs are tightly linked to rearrangements of the host cell cytoskeleton.",2017 Feb 28,"['Cortese, Mirko', 'Goellner, Sarah', 'Acosta, Eliana Gisela', 'Neufeldt, Christopher John', 'Oleksiuk, Olga', 'Lampe, Marko', 'Haselmann, Uta', 'Funaya, Charlotta', 'Schieber, Nicole', 'Ronchi, Paolo', 'Schorb, Martin', 'Pruunsild, Priit', 'Schwab, Yannick', 'Chatel-Chaix, Laurent', 'Ruggieri, Alessia', 'Bartenschlager, Ralf']",Cell Rep,,,True
6a3fa8ed278df0d05c5e009521de11c72308f60b,PMC,A systematic review of the effectiveness of antimicrobial rinse-free hand sanitizers for prevention of illness-related absenteeism in elementary school children,http://dx.doi.org/10.1186/1471-2458-4-50,PMC534108,15518593,CC BY,"BACKGROUND: Absenteeism due to communicable illness is a major problem encountered by North American elementary school children. Although handwashing is a proven infection control measure, barriers exist in the school environment, which hinder compliance to this routine. Currently, alternative hand hygiene techniques are being considered, and one such technique is the use of antimicrobial rinse-free hand sanitizers. METHODS: A systematic review was conducted to examine the effectiveness of antimicrobial rinse-free hand sanitizer interventions in the elementary school setting. MEDLINE, EMBASE, Biological Abstract, CINAHL, HealthSTAR and Cochrane Controlled Trials Register were searched for both randomized and non-randomized controlled trials. Absenteeism due to communicable illness was the primary outcome variable. RESULTS: Six eligible studies, two of which were randomized, were identified (5 published studies, 1 published abstract). The quality of reporting was low. Due to a large amount of heterogeneity and low quality of reporting, no pooled estimates were calculated. There was a significant difference reported in favor of the intervention in all 5 published studies. CONCLUSIONS: The available evidence for the effectiveness of antimicrobial rinse-free hand sanitizer in the school environment is of low quality. The results suggest that the strength of the benefit should be interpreted with caution. Given the potential to reduce student absenteeism, teacher absenteeism, school operating costs, healthcare costs and parental absenteeism, a well-designed and analyzed trial is needed to optimize this hand hygiene technique.",2004 Nov 1,"['Meadows, Emily', 'Le Saux, Nicole']",BMC Public Health,,,True
365b0a8e08cc9c93c6e5b33e23ef3d4399953870,PMC,Worry experienced during the 2015 Middle East Respiratory Syndrome (MERS) pandemic in Korea,http://dx.doi.org/10.1371/journal.pone.0173234,PMC5342218,28273131,CC BY,"BACKGROUND: Korea failed in its risk communication during the early stage of the Middle East Respiratory Syndrome (MERS) outbreak; consequently, it faced difficulties in managing MERS, while disease-related worry increased. Disease-related worry can help disease prevention and management, but can also have a detrimental effect. This study measured the overall level of disease-related worry during the MERS outbreak period in Korea and the influencing factors and levels of disease-related worry during key outbreak periods. METHODS: The cross-sectional survey included 1,000 adults who resided in Korea. An ordinal logistic regression was performed for the overall level of MERS-related worry, and influencing factors of worry were analyzed. A reliability test was performed on the levels of MERS-related worry during key outbreak periods. RESULTS: The overall level of MERS-related worry was 2.44. Multivariate analysis revealed that women and respondents w very poor subjective health status had higher levels of worry. Respondents with very high stress in daily life had higher levels of worry than those who reported having little stress. The reliability test results on MERS-related worry scores during key outbreak periods showed consistent scores during each period. CONCLUSION: Level of worry increased in cases having higher perceived susceptibility and greater trust in informal information, while initial stage of outbreak was closely associated with that at later stages. These findings suggest the importance of managing the level of worry by providing timely and accurate disease-related information during the initial stage of disease outbreak.",2017 Mar 8,"['Ro, Jun-Soo', 'Lee, Jin-Seok', 'Kang, Sung-Chan', 'Jung, Hye-Min']",PLoS One,,,True
8c1f89ee9ab589642a59a2dc4bad30db7227f484,PMC,Worry experienced during the 2015 Middle East Respiratory Syndrome (MERS) pandemic in Korea,http://dx.doi.org/10.1371/journal.pone.0173234,PMC5342218,28273131,CC BY,"BACKGROUND: Korea failed in its risk communication during the early stage of the Middle East Respiratory Syndrome (MERS) outbreak; consequently, it faced difficulties in managing MERS, while disease-related worry increased. Disease-related worry can help disease prevention and management, but can also have a detrimental effect. This study measured the overall level of disease-related worry during the MERS outbreak period in Korea and the influencing factors and levels of disease-related worry during key outbreak periods. METHODS: The cross-sectional survey included 1,000 adults who resided in Korea. An ordinal logistic regression was performed for the overall level of MERS-related worry, and influencing factors of worry were analyzed. A reliability test was performed on the levels of MERS-related worry during key outbreak periods. RESULTS: The overall level of MERS-related worry was 2.44. Multivariate analysis revealed that women and respondents w very poor subjective health status had higher levels of worry. Respondents with very high stress in daily life had higher levels of worry than those who reported having little stress. The reliability test results on MERS-related worry scores during key outbreak periods showed consistent scores during each period. CONCLUSION: Level of worry increased in cases having higher perceived susceptibility and greater trust in informal information, while initial stage of outbreak was closely associated with that at later stages. These findings suggest the importance of managing the level of worry by providing timely and accurate disease-related information during the initial stage of disease outbreak.",2017 Mar 8,"['Ro, Jun-Soo', 'Lee, Jin-Seok', 'Kang, Sung-Chan', 'Jung, Hye-Min']",PLoS One,,,False
5b5b00bae35df86219432dc63111ae30715f6ca4,PMC,Worry experienced during the 2015 Middle East Respiratory Syndrome (MERS) pandemic in Korea,http://dx.doi.org/10.1371/journal.pone.0173234,PMC5342218,28273131,CC BY,"BACKGROUND: Korea failed in its risk communication during the early stage of the Middle East Respiratory Syndrome (MERS) outbreak; consequently, it faced difficulties in managing MERS, while disease-related worry increased. Disease-related worry can help disease prevention and management, but can also have a detrimental effect. This study measured the overall level of disease-related worry during the MERS outbreak period in Korea and the influencing factors and levels of disease-related worry during key outbreak periods. METHODS: The cross-sectional survey included 1,000 adults who resided in Korea. An ordinal logistic regression was performed for the overall level of MERS-related worry, and influencing factors of worry were analyzed. A reliability test was performed on the levels of MERS-related worry during key outbreak periods. RESULTS: The overall level of MERS-related worry was 2.44. Multivariate analysis revealed that women and respondents w very poor subjective health status had higher levels of worry. Respondents with very high stress in daily life had higher levels of worry than those who reported having little stress. The reliability test results on MERS-related worry scores during key outbreak periods showed consistent scores during each period. CONCLUSION: Level of worry increased in cases having higher perceived susceptibility and greater trust in informal information, while initial stage of outbreak was closely associated with that at later stages. These findings suggest the importance of managing the level of worry by providing timely and accurate disease-related information during the initial stage of disease outbreak.",2017 Mar 8,"['Ro, Jun-Soo', 'Lee, Jin-Seok', 'Kang, Sung-Chan', 'Jung, Hye-Min']",PLoS One,,,False
968b32a7e4c4d6ec64f01fab3e247e4114a32490,PMC,Porcine epidemic diarrhea virus nucleoprotein contributes to HMGB1 transcription and release by interacting with C/EBP-β,http://dx.doi.org/10.18632/oncotarget.11991,PMC5342723,27634894,CC BY,"Porcine epidemic diarrhea is a devastating swine enteric disease, which is caused by porcine epidemic diarrhea virus (PEDV) infection. Our studies demonstrated that PEDV infection resulted in the up-regulation of proinflammatory cytokines. Meanwhile, PEDV infection and overexpression of viral nucleoprotein resulted in the acetylation and release of high mobility group box 1 proteins in vitro, an important proinflammatory response mediator, which contributes to the pathogenesis of various inflammatory diseases. Our studies also showed that SIRT1, histone acetyltransferase, and NF-κB regulated the acetylation and release of HMGB1. Chromatin immunoprecipitation, dual-luciferase reporter gene assay, and co-immunoprecipitation experiments illustrated that PEDV-N could induce HMGB1 transcription by interacting with C/EBP-β, which could bind to C/EBP motif in HMGB1 promotor region. Collectively, our data indicate PEDV-N contributes to HMGB1 transcription and the subsequent release/acetylation of HMGB1 during PEDV infection.",2016 Sep 13,"['Huan, Chang-chao', 'Wang, Hua-xia', 'Sheng, Xiang-xiang', 'Wang, Rui', 'Wang, Xin', 'Liao, Ying', 'Liu, Qin-fang', 'Tong, Guang-zhi', 'Ding, Chan', 'Fan, Hong-jie', 'Wu, Jia-qiang', 'Mao, Xiang']",Oncotarget,,,True
7360f5cfdd468aea794a9eb68291950862c8fcb0,PMC,Characterization of Chinese Porcine Epidemic Diarrhea Virus with Novel Insertions and Deletions in Genome,http://dx.doi.org/10.1038/srep44209,PMC5343579,28276526,CC BY,"Outbreaks of porcine epidemic diarrhoea virus (PEDV) have caused great economic losses to the global pig industry. PEDV strains with variants in the spike (S) gene have been reported in several countries. To better understand the molecular epidemiology and genetic diversity of PEDV field isolates, in this study, we characterised the complete genome sequence of a novel PEDV variant JSCZ1601 from a outbreak in China in 2016. The PEDV isolate was 28,033 nucleotides (nt) in length without the polyadenylated sequences. Phylogenetic analysis based on the full-length genome sequence of JSCZ1601 grouped it with the pandemic variants determined post-2010 into group 2 (G2). However, the S gene of JSCZ1601 formed a new subgroup separated from the subgroups containing the other G2 strains. Comparative analysis of the amino acids encoded by the S genes revealed the N-terminal of the deduced JSCZ1601 S protein had a novel two-amino-acid deletion (N58 and S59) compared with all identified genogroups. Further, compared with the reference strains, a ‘G’ insertion was detected in the 5′ terminal of the 5′UTR of the JSCZ1601. The animal experiment revealed that this strain was high pathogenic to neonatal pigs. Taken together, a PEDV strain with the new molecular characterizations and phylogenies was found in mainland China. It is necessary to strengthen the monitoring of PEDV variations.",2017 Mar 9,"['Fan, Baochao', 'Jiao, Dian', 'Zhao, Xiaona', 'Pang, Fengjiao', 'Xiao, Qi', 'Yu, Zhengyu', 'Mao, Aihua', 'Guo, Rongli', 'Yuan, Wanzhe', 'Zhao, Pandeng', 'He, Kongwang', 'Li, Bin']",Sci Rep,,,True
8ed6b522481e264a5d691f7f5fbd5d142b5f82f7,PMC,"Pneumonia, Acute Respiratory Distress Syndrome, and Early Immune-Modulator Therapy",http://dx.doi.org/10.3390/ijms18020388,PMC5343923,28208675,CC BY,"Acute respiratory distress syndrome (ARDS) is caused by infectious insults, such as pneumonia from various pathogens or related to other noninfectious events. Clinical and histopathologic characteristics are similar across severely affected patients, suggesting that a common mode of immune reaction may be involved in the immunopathogenesis of ARDS. There may be etiologic substances that have an affinity for respiratory cells and induce lung cell injury in cases of ARDS. These substances originate not only from pathogens, but also from injured host cells. At the molecular level, these substances have various sizes and biochemical characteristics, classifying them as protein substances and non-protein substances. Immune cells and immune proteins may recognize and act on these substances, including pathogenic proteins and peptides, depending upon the size and biochemical properties of the substances (this theory is known as the protein-homeostasis-system hypothesis). The severity or chronicity of ARDS depends on the amount of etiologic substances with corresponding immune reactions, the duration of the appearance of specific immune cells, or the repertoire of specific immune cells that control the substances. Therefore, treatment with early systemic immune modulators (corticosteroids and/or intravenous immunoglobulin) as soon as possible may reduce aberrant immune responses in the potential stage of ARDS.",2017 Feb 11,"Lee, Kyung-Yil",Int J Mol Sci,,,True
6e8e102a4453c1bf7d9d4886d32d6aa1bebb3e53,PMC,Transfer of Anti-Rotavirus Antibodies during Pregnancy and in Milk Following Maternal Vaccination with a Herpes Simplex Virus Type-1 Amplicon Vector,http://dx.doi.org/10.3390/ijms18020431,PMC5343965,28212334,CC BY,"Rotaviruses (RVs) are important enteric pathogens of newborn humans and animals, causing diarrhea and in rare cases death, especially in very young individuals. Rotavirus vaccines presently used are modified live vaccines that lack complete biological safety. Previous work from our laboratory suggested that vaccines based on in situ produced, non-infectious rotavirus-like particles (RVLPs) are efficient while being entirely safe. However, using either vaccine, active mucosal immunization cannot induce protective immunity in newborns due to their immature immune system. We therefore hypothesized that offspring from vaccinated dams are passively immunized either by transfer of maternal antibodies during pregnancy or by taking up antibodies from milk. Using a codon optimized polycistronic gene expression cassette packaged into herpesvirus particles, the simultaneous expression of the RV capsid genes led to the intracellular formation of RVLPs in various cell lines. Vaccinated dams developed a strong RV specific IgG antibody response determined in sera and milk of both mother and pups. Moreover, sera of naïve pups nursed by vaccinated dams also had RV specific antibodies suggesting a lactogenic transfer of antibodies. Although full protection of pups was not achieved in this mouse model, our observations are important for the development of improved vaccines against RV in humans as well as in various animal species.",2017 Feb 16,"['Meier, Anita F.', 'Suter, Mark', 'Schraner, Elisabeth M.', 'Humbel, Bruno M.', 'Tobler, Kurt', 'Ackermann, Mathias', 'Laimbacher, Andrea S.']",Int J Mol Sci,,,True
7293d0d1c84570d510be54e720daecfcf7a77990,PMC,PBMC transcriptome profiles identifies potential candidate genes and functional networks controlling the innate and the adaptive immune response to PRRSV vaccine in Pietrain pig,http://dx.doi.org/10.1371/journal.pone.0171828,PMC5344314,28278192,CC BY,"The porcine reproductive and respiratory syndrome (PRRS) is a devastating viral disease affecting swine production, health and welfare throughout the world. A synergistic action of the innate and the adaptive immune system of the host is essential for mounting a durable protective immunity through vaccination. Therefore, the current study aimed to investigate the transcriptome profiles of peripheral blood mononuclear cells (PBMCs) to characterize the innate and the adaptive immune response to PRRS Virus (PRRSV) vaccination in Pietrain pigs. The Affymetrix gene chip porcine gene 1.0 ST array was used for the transcriptome profiling of PBMCs collected at immediately before (D0), at one (D1) and 28 days (D28) post PRRSV vaccination with three biological replications. With FDR <0.05 and log2 fold change ±1.5 as cutoff criteria, 295 and 115 transcripts were found to be differentially expressed in PBMCs during the stage of innate and adaptive response, respectively. The microarray expression results were technically validated by qRT-PCR. The gene ontology terms such as viral life cycle, regulation of lymphocyte activation, cytokine activity and inflammatory response were enriched during the innate immunity; cytolysis, T cell mediated cytotoxicity, immunoglobulin production were enriched during adaptive immunity to PRRSV vaccination. Significant enrichment of cytokine-cytokine receptor interaction, signaling by interleukins, signaling by the B cell receptor (BCR), viral mRNA translation, IFN-gamma pathway and AP-1 transcription factor network pathways were indicating the involvement of altered genes in the antiviral defense. Network analysis revealed that four network modules were functionally involved with the transcriptional network of innate immunity, and five modules were linked to adaptive immunity in PBMCs. The innate immune transcriptional network was found to be regulated by LCK, STAT3, ATP5B, UBB and RSP17. While TGFß1, IL7R, RAD21, SP1 and GZMB are likely to be predictive for the adaptive immune transcriptional response to PRRSV vaccine in PBMCs. Results of the current immunogenomics study advances our understanding of PRRS in term of host-vaccine interaction, and thereby contribute to design a rationale for disease control strategy.",2017 Mar 9,"['Islam, Md. Aminul', 'Große-Brinkhaus, Christine', 'Pröll, Maren Julia', 'Uddin, Muhammad Jasim', 'Aqter Rony, Sharmin', 'Tesfaye, Dawit', 'Tholen, Ernst', 'Hoelker, Michael', 'Schellander, Karl', 'Neuhoff, Christiane']",PLoS One,,,True
6efcaa639a97ba506cf341230c166208d1312a11,PMC,Structure of a pentameric virion-associated fiber with a potential role in Orsay virus entry to host cells,http://dx.doi.org/10.1371/journal.ppat.1006231,PMC5344674,28241071,CC BY,"Despite the wide use of Caenorhabditis elegans as a model organism, the first virus naturally infecting this organism was not discovered until six years ago. The Orsay virus and its related nematode viruses have a positive-sense RNA genome, encoding three proteins: CP, RdRP, and a novel δ protein that shares no homology with any other proteins. δ can be expressed either as a free δ or a CP-δ fusion protein by ribosomal frameshift, but the structure and function of both δ and CP-δ remain unknown. Using a combination of electron microscopy, X-ray crystallography, computational and biophysical analyses, here we show that the Orsay δ protein forms a ~420-Å long, pentameric fiber with an N-terminal α-helical bundle, a β-stranded filament in the middle, and a C-terminal head domain. The pentameric nature of the δ fiber has been independently confirmed by both mass spectrometry and analytical ultracentrifugation. Recombinant Orsay capsid containing CP-δ shows protruding long fibers with globular heads at the distal end. Mutant viruses with disrupted CP-δ fibers were generated by organism-based reverse genetics. These viruses were found to be either non-viable or with poor infectivity according to phenotypic and qRT-PCR analyses. Furthermore, addition of purified δ proteins to worm culture greatly reduced Orsay infectivity in a sequence-specific manner. Based on the structure resemblance between the Orsay CP-δ fiber and the fibers from reovirus and adenovirus, we propose that CP-δ functions as a cell attachment protein to mediate Orsay entry into worm intestine cells.",2017 Feb 27,"['Fan, Yanlin', 'Guo, Yusong R.', 'Yuan, Wang', 'Zhou, Ying', 'Holt, Matthew V.', 'Wang, Tao', 'Demeler, Borries', 'Young, Nicolas L.', 'Zhong, Weiwei', 'Tao, Yizhi J.']",PLoS Pathog,,,True
ef720b08c80cb574e3db1e48be65750ebb4b5104,PMC,Type I Interferons as Regulators of Lung Inflammation,http://dx.doi.org/10.3389/fimmu.2017.00259,PMC5344902,28344581,CC BY,"Immune responses to lung infections must be tightly regulated in order to permit pathogen eradication while maintaining organ function. Exuberant or dysregulated inflammation can impair gas exchange and underlies many instances of lung disease. An important driver of inflammation in the lung is the interferon (IFN) response. Type I IFNs are antiviral cytokines that induce a large range of proteins that impair viral replication in infected cells. This cell-intrinsic action plays a crucial role in protecting the lungs from spread of respiratory viruses. However, type I IFNs have also recently been found to be central to the initiation of lung inflammatory responses, by inducing recruitment and activation of immune cells. This helps control virus burden but can cause detrimental immunopathology and contribute to disease severity. Furthermore, there is now increasing evidence that type I IFNs are not only induced after viral infections but also after infection with bacteria and fungi. The pro-inflammatory function of type I IFNs in the lung opens up the possibility of immune modulation directed against this antiviral cytokine family. In this review, the initiation and signaling of type I IFNs as well as their role in driving and maintaining lung inflammation will be discussed.",2017 Mar 10,"['Makris, Spyridon', 'Paulsen, Michelle', 'Johansson, Cecilia']",Front Immunol,,,True
65aa725092d0b73054cce187137a0c22afb92d10,PMC,Pathogenetic determinants in Kawasaki disease: the haematological point of view,http://dx.doi.org/10.1111/jcmm.12992,PMC5345614,28063205,CC BY,"Kawasaki disease is a multisystemic vasculitis that can result in coronary artery lesions. It predominantly affects young children and is characterized by prolonged fever, diffuse mucosal inflammation, indurative oedema of the hands and feet, a polymorphous skin rash and non‐suppurative lymphadenopathy. Coronary artery involvement is the most important complication of Kawasaki disease and may cause significant coronary stenosis resulting in ischemic heart disease. The introduction of intravenous immunoglobulin decreases the incidence of coronary artery lesions to less than 5%. The etiopathogenesis of this disease remains unclear. Several lines of evidence suggest that an interplay between a microbial infection and a genetic predisposition could take place in the development of the disease. In this review, we summarize the state of the art of pathogenetic mechanisms of Kawasaki disease underscoring the relevance of haematological features as a novel field of investigation.",2017 Apr 7,"['Del Principe, Domenico', 'Pietraforte, Donatella', 'Gambardella, Lucrezia', 'Marchesi, Alessandra', 'Tarissi de Jacobis, Isabella', 'Villani, Alberto', 'Malorni, Walter', 'Straface, Elisabetta']",J Cell Mol Med,,,True
e15c8f5664f0a614345b976780eeea291b282fd1,PMC,Lentivirus-mediated RNAi knockdown of insulin-like growth factor-1 receptor inhibits the growth and invasion of hepatocellular carcinoma via down-regulating midkine expression,http://dx.doi.org/10.18632/oncotarget.13027,PMC5346715,27813495,CC BY,"The insulin-like growth factor-1 receptor (IGF-1R) overexpression contributes to the development of a variety of cancers. The present study explored the role of IGF-1R in the development and progression of hepatocellular carcinoma (HCC) and the possibility of IGF-1R silencing by lentivirus-mediated RNA interference (RNAi) as a therapeutic target for HCC. We showed that IGF-1R mRNA was up-regulated in Huh7 and Hep3B cells and human HCC tissues, and that IGF-1R knockdown by RNAi led to decreased proliferation, apoptosis induction, and decreased migration and invasion of Huh7 and Hep3B cells. Further, the in vivo study indicated that IGF-1R knockdown markedly diminished the tumorigenesis and metastasis of Huh7 xenograft. Moreover, the intratumoral administration of lentivirus-IGF-1R siRNA led to significant tumor growth inhibition in an established Huh7 xenograft model. Mechanistic investigations showed that midkine was found to be the most significantly down-regulated protein in Huh7 cells with IGF-1R knockdown, and ectopic overexpression of midkine significantly rescued inhibition of Huh7 cell proliferation, migration, and invasion caused by IGF-1R suppression. Collectively, these data suggest that IGF-1R inhibition by RNAi can significantly suppress HCC growth and invasion at least partially through down-regulating midkine expression, and IGF-1R is a potential target for HCC gene therapy.",2016 Nov 2,"['Bie, Cai Qun', 'Liu, Xu You', 'Cao, Ming Rong', 'Huang, Qiu Yan', 'Tang, Hui Jun', 'Wang, Min', 'Cao, Guo Li', 'Yi, Ting Zhuang', 'Wu, Sheng Lan', 'Xu, Wei Jie', 'Tang, Shao Hui']",Oncotarget,,,True
31fabefa068bca926a43f94ef80df1daf41aa806,PMC,An in vivo system for directed experimental evolution of rabbit haemorrhagic disease virus,http://dx.doi.org/10.1371/journal.pone.0173727,PMC5348035,28288206,CC BY,"The calicivirus Rabbit haemorrhagic disease virus (RHDV) is widely used in Australia as a biocontrol agent to manage wild European rabbit (Oryctolagus cuniculus) populations. However, widespread herd immunity limits the effectiveness of the currently used strain, CAPM V-351. To overcome this, we developed an experimental platform for the selection and characterisation of novel RHDV strains. As RHDV does not replicate in cell culture, variant viruses were selected by serially passaging a highly virulent RHDV field isolate in immunologically naïve laboratory rabbits that were passively immunised 18–24 hours post-challenge with a neutralising monoclonal antibody. After seven passages, two amino acid substitutions in the P2 domain of the capsid protein became fixed within the virus population. Furthermore, a synonymous substitution within the coding sequence of the viral polymerase appeared and was also maintained in all subsequent passages. These findings demonstrate proof-of-concept that RHDV evolution can be experimentally manipulated to select for virus variants with altered phenotypes, in this case partial immune escape.",2017 Mar 13,"['Hall, Robyn N.', 'Capucci, Lorenzo', 'Matthaei, Markus', 'Esposito, Simona', 'Kerr, Peter J.', 'Frese, Michael', 'Strive, Tanja']",PLoS One,,,True
fac028a97db9169282fd01c3ca41d4eb7afb3f5c,PMC,Type I and III Interferon in the Gut: Tight Balance between Host Protection and Immunopathology,http://dx.doi.org/10.3389/fimmu.2017.00258,PMC5348535,28352268,CC BY,"The intestinal mucosa forms an active interface to the outside word, facilitating nutrient and water uptake and at the same time acts as a barrier toward the highly colonized intestinal lumen. A tight balance of the mucosal immune system is essential to tolerate harmless antigens derived from food or commensals and to effectively defend against potentially dangerous pathogens. Interferons (IFN) provide a first line of host defense when cells detect an invading organism. Whereas type I IFN were discovered almost 60 years ago, type III IFN were only identified in the early 2000s. It was initially thought that type I IFN and type III IFN performed largely redundant functions. However, it is becoming increasingly clear that type III IFN exert distinct and non-redundant functions compared to type I IFN, especially in mucosal tissues. Here, we review recent progress made in unraveling the role of type I/III IFN in intestinal mucosal tissue in the steady state, in response to mucosal pathogens and during inflammation.",2017 Mar 14,"['Pott, Johanna', 'Stockinger, Silvia']",Front Immunol,,,True
0234207cba8165f1e1852b92ae0fa0d9e2f870fb,PMC,Disease dynamics in a stochastic network game: a little empathy goes a long way in averting outbreaks,http://dx.doi.org/10.1038/srep44122,PMC5349521,28290504,CC BY,"Individuals change their behavior during an epidemic in response to whether they and/or those they interact with are healthy or sick. Healthy individuals may utilize protective measures to avoid contracting a disease. Sick individuals may utilize preemptive measures to avoid spreading a disease. Yet, in practice both protective and preemptive changes in behavior come with costs. This paper proposes a stochastic network disease game model that captures the self-interests of individuals during the spread of a susceptible-infected-susceptible disease. In this model, individuals strategically modify their behavior based on current disease conditions. These reactions influence disease spread. We show that there is a critical level of concern, i.e., empathy, by the sick individuals above which disease is eradicated rapidly. Furthermore, we find that risk averse behavior by the healthy individuals cannot eradicate the disease without the preemptive measures of the sick individuals. Empathy is more effective than risk-aversion because when infectious individuals change behavior, they reduce all of their potential infections, whereas when healthy individuals change behavior, they reduce only a small portion of potential infections. This imbalance in the role played by the response of the infected versus the susceptible individuals on disease eradication affords critical policy insights.",2017 Mar 14,"['Eksin, Ceyhun', 'Shamma, Jeff S.', 'Weitz, Joshua S.']",Sci Rep,,,True
c751c8772ce889d767d8896227d82d3f8f5f3bab,PMC,Disease dynamics in a stochastic network game: a little empathy goes a long way in averting outbreaks,http://dx.doi.org/10.1038/srep44122,PMC5349521,28290504,CC BY,"Individuals change their behavior during an epidemic in response to whether they and/or those they interact with are healthy or sick. Healthy individuals may utilize protective measures to avoid contracting a disease. Sick individuals may utilize preemptive measures to avoid spreading a disease. Yet, in practice both protective and preemptive changes in behavior come with costs. This paper proposes a stochastic network disease game model that captures the self-interests of individuals during the spread of a susceptible-infected-susceptible disease. In this model, individuals strategically modify their behavior based on current disease conditions. These reactions influence disease spread. We show that there is a critical level of concern, i.e., empathy, by the sick individuals above which disease is eradicated rapidly. Furthermore, we find that risk averse behavior by the healthy individuals cannot eradicate the disease without the preemptive measures of the sick individuals. Empathy is more effective than risk-aversion because when infectious individuals change behavior, they reduce all of their potential infections, whereas when healthy individuals change behavior, they reduce only a small portion of potential infections. This imbalance in the role played by the response of the infected versus the susceptible individuals on disease eradication affords critical policy insights.",2017 Mar 14,"['Eksin, Ceyhun', 'Shamma, Jeff S.', 'Weitz, Joshua S.']",Sci Rep,,,True
cbb02b21e4165b060929344f2f02ab6859016be3,PMC,"Causes of variability in prevalence rates of communicable diseases among secondary school Students in Kisumu County, Kenya",http://dx.doi.org/10.1007/s10389-016-0777-9,PMC5350242,28357195,CC BY,"PURPOSE: To determine causes of variability in communicable disease prevalence rates among students in secondary schools to inform policy formulation in the public health sector. METHODS: A representative cluster sample size for students was estimated using Fisher et al.’s formula while schools, sub-counties and education zones were clustered and sample size was calculated based on coefficient of variation by school type. Data were collected by questionnaire, medical examination using standard procedures, and focus group discussion, and descriptive analysis was performed on the completed questions. Comparisons between risk factors were made by chi-square and ANOVA analysis using SPSS for Windows (version 15.2; Chicago, IL) software. A p value of < 0.05 was considered statistically significant. RESULTS: There was significant variation between communicable disease prevalence rates and age (X(2) (4, 0.05) = 2.458), school size (X(2) (12, 0.05) = 18.636), gender (X(2) (4, 0.05) = 5.723) and class of students (X(2) (12, 0.05) = 15.202), and bed and desk spacing (p < 0.05 at 95% CI). However, there was no significant association in prevalence rates between both locality and type of school. There was strong evidence that student age has an effect on prevalence rates. The prevalence rate of malaria was higher in male (14.02%) than female students (6.68%) compared to prevalence of diarrhea, which was higher in female (7.96%) than male students. CONCLUSION: This study has revealed that the prevalences of diarrhea, tuberculosis, pneumonia and other respiratory tract infections are lower among female secondary school students than males and that the prevalence of malaria is higher in males than females. Age of secondary school students is a significant vulnerability factor for malaria, diarrhea, tuberculosis and pneumonia, which were the important communicable diseases most prevalent among secondary school students in Kisumu County, Kenya.",2017 Dec 3,"['Odongo, David Otieno', 'Wakhungu, W. J.', 'Stanley, Omuterema']",Z Gesundh Wiss,,,True
b2d1fbbdf2e7ff09c09119e4d49f3f60e9091101,PMC,A Simulation Study on Hypothetical Ebola Virus Transmission in India Using Spatiotemporal Epidemiological Modeler (STEM): A Way towards Precision Public Health,http://dx.doi.org/10.1155/2017/7602301,PMC5350287,28348606,CC BY,"Background. Precision public health is a state-of-the-art concept in public health research and its application in health care. Application of information technology in field of epidemiology paves the way to its transformation to digital epidemiology. A geospatial epidemiological model was simulated to estimate the spread of Ebola virus disease after a hypothetical outbreak in India. Methods. It was a simulation study based on SEIR (Susceptible-Exposed-Infectious-Recovered) compartmental model. Simulation was done in Spatiotemporal Epidemiological Modeler (STEM). Epidemiological profile of Ebola virus, that transmitted throughout the Sierra Leon in 2014–2016, was fitted into the SEIR deterministic compartment model designed for India. Result. Spatiotemporal distribution of EVD exposed, infectious, and recovered population at 4-month interval represented by different figures. It is estimated that if no intervention is taken to stop the spread, within 2 years, almost half of the country will be effected by EVD and cumulative number of exposed individuals, infectious persons, and deaths will be 106947760, 30651674, and 18391005, respectively. Conclusion. Precision public health may play the key role to achieve the health related targets in the Sustainable Development Goals. Policy makers, public health specialists, and data scientists need to put their hands together to make precision public health a reality.",2017 Feb 27,"Sau, Arkaprabha",J Environ Public Health,,,True
97ab5bad794553f1af287d9ee88c0113e1ba80ed,PMC,Patterns of Human Respiratory Viruses and Lack of MERS-Coronavirus in Patients with Acute Upper Respiratory Tract Infections in Southwestern Province of Saudi Arabia,http://dx.doi.org/10.1155/2017/4247853,PMC5350310,28348590,CC BY,"We undertook enhanced surveillance of those presenting with respiratory symptoms at five healthcare centers by testing all symptomatic outpatients between November 2013 and January 2014 (winter time). Nasal swabs were collected from 182 patients and screened for MERS-CoV as well as other respiratory viruses using RT-PCR and multiplex microarray. A total of 75 (41.2%) of these patients had positive viral infection. MERS-CoV was not detected in any of the samples. Human rhinovirus (hRV) was the most detected pathogen (40.9%) followed by non-MERS-CoV human coronaviruses (19.3%), influenza (Flu) viruses (15.9%), and human respiratory syncytial virus (hRSV) (13.6%). Viruses differed markedly depending on age in which hRV, Flu A, and hCoV-OC43 were more prevalent in adults and RSV, hCoV-HKU1, and hCoV-NL63 were mostly restricted to children under the age of 15. Moreover, coinfection was not uncommon in this study, in which 17.3% of the infected patients had dual infections due to several combinations of viruses. Dual infections decreased with age and completely disappeared in people older than 45 years. Our study confirms that MERS-CoV is not common in the southwestern region of Saudi Arabia and shows high diversity and prevalence of other common respiratory viruses. This study also highlights the importance and contribution of enhanced surveillance systems for better infection control.",2017 Feb 27,"['Abdulhaq, Ahmed A.', 'Basode, Vinod Kumar', 'Hashem, Anwar M.', 'Alshrari, Ahmed S.', 'Badroon, Nassrin A.', 'Hassan, Ahmed M.', 'Alsubhi, Tagreed L.', 'Solan, Yahia', 'Ejeeli, Saleh', 'Azhar, Esam I.']",Adv Virol,,,True
a54f0ac7bdf236b56f8766f1a4ac20130728b187,PMC,Lysophosphatidic Acid Triggers Apoptosis in HeLa Cells through the Upregulation of Tumor Necrosis Factor Receptor Superfamily Member 21,http://dx.doi.org/10.1155/2017/2754756,PMC5350427,28348459,CC BY,"Lysophosphatidic acid (LPA), a naturally occurring bioactive phospholipid, activates G protein-coupled receptors (GPCRs), leading to regulation of diverse cellular events including cell survival and apoptosis. Despite extensive studies of the signaling pathways that mediate LPA-regulated cell growth and survival, the mechanisms underlying the apoptotic effect of LPA remain largely unclear. In this study, we investigated this issue in HeLa cells. Our data demonstrate that LPA induces apoptosis in HeLa cells at pathologic concentrations with a concomitant upregulation of the expression of TNFRSF21 (tumor necrosis factor receptor superfamily member 21), also known as death receptor number 6 (DR6) involved in inflammation. Moreover, treatment of cells with LPA receptor (LPAR) antagonist abolished the DR6 upregulation by LPA. LPA-induced DR6 expression was also abrogated by pertussis toxin (PTX), an inhibitor of GPCRs, and by inhibitors of PI3K, PKC, MEK, and ERK. Intriguingly, LPA-induced DR6 expression was specifically blocked by dominant-negative form of PKCδ (PKCδ-DN). LPA-induced DR6 expression was also dramatically inhibited by knockdown of ERK or CREB. These results suggest that activation of the MEK/ERK pathway and the transcription factor CREB mediate LPA-induced DR6 expression. More interestingly, knockdown of DR6 using siRNA approach remarkably attenuated LPA-induced apoptosis. In conclusion, our results suggest that LPA-induced apoptosis in HeLa cells is mediated by the upregulation of DR6 expression.",2017 Feb 19,"['Dong, Yunzhou', 'Wu, Yong', 'Cui, Mei-Zhen', 'Xu, Xuemin']",Mediators Inflamm,,,False
670f2388055a866aa6706a2c1130d68c2f37d15d,PMC,Lysophosphatidic Acid Triggers Apoptosis in HeLa Cells through the Upregulation of Tumor Necrosis Factor Receptor Superfamily Member 21,http://dx.doi.org/10.1155/2017/2754756,PMC5350427,28348459,CC BY,"Lysophosphatidic acid (LPA), a naturally occurring bioactive phospholipid, activates G protein-coupled receptors (GPCRs), leading to regulation of diverse cellular events including cell survival and apoptosis. Despite extensive studies of the signaling pathways that mediate LPA-regulated cell growth and survival, the mechanisms underlying the apoptotic effect of LPA remain largely unclear. In this study, we investigated this issue in HeLa cells. Our data demonstrate that LPA induces apoptosis in HeLa cells at pathologic concentrations with a concomitant upregulation of the expression of TNFRSF21 (tumor necrosis factor receptor superfamily member 21), also known as death receptor number 6 (DR6) involved in inflammation. Moreover, treatment of cells with LPA receptor (LPAR) antagonist abolished the DR6 upregulation by LPA. LPA-induced DR6 expression was also abrogated by pertussis toxin (PTX), an inhibitor of GPCRs, and by inhibitors of PI3K, PKC, MEK, and ERK. Intriguingly, LPA-induced DR6 expression was specifically blocked by dominant-negative form of PKCδ (PKCδ-DN). LPA-induced DR6 expression was also dramatically inhibited by knockdown of ERK or CREB. These results suggest that activation of the MEK/ERK pathway and the transcription factor CREB mediate LPA-induced DR6 expression. More interestingly, knockdown of DR6 using siRNA approach remarkably attenuated LPA-induced apoptosis. In conclusion, our results suggest that LPA-induced apoptosis in HeLa cells is mediated by the upregulation of DR6 expression.",2017 Feb 19,"['Dong, Yunzhou', 'Wu, Yong', 'Cui, Mei-Zhen', 'Xu, Xuemin']",Mediators Inflamm,,,True
b4fc836f8970f271a9cdee3604b53f9f1f2a55ab,PMC,Uniquely conserved immunosuppressive viral exoribonucleases,http://dx.doi.org/10.18632/oncotarget.14548,PMC5351563,28077798,CC BY,,2017 Jan 6,"['Meyer, Bjoern', 'Ly, Hinh']",Oncotarget,,,False
ed3dac12ca72f06c51d7f68ae5fe6aaaa6f3e740,PMC,"The Expression of IL-6, TNF-α, and MCP-1 in Respiratory Viral Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease",http://dx.doi.org/10.1155/2017/8539294,PMC5352889,28352642,CC BY,"Viral infection is a common trigger for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of this study is to investigate the expression of cytokines in AECOPD. Patients with AECOPD requiring hospitalization were recruited. Meanwhile healthy volunteers of similar age that accepted routine check-ups and showed no clinical symptoms of inflammatory diseases were also recruited. Induced sputum and serum were collected. Induced sputum of participants was processed and tested for thirteen viruses and bacteria. Forty cytokines were assayed in serum using the Quantibody Human Inflammation Array 3 (Ray Biotech, Inc.). The most common virus detected in virus positive AECOPD (VP) was influenza A (16%). No virus was found in controls. Circulating levels of IL-6, TNF-α, and MCP-1 were elevated in VP and coinfection subjects (p < 0.05), while the levels of 37 other cytokines showed no difference, compared with virus negative groups and controls (p > 0.05). Additionally, VP patients were less likely to have received influenza vaccination. VP patients had a systemic inflammation response involving IL-6, TNF-α, and MCP-1 which may be due to virus-induced activation of macrophages. There are important opportunities for further investigating AECOPD mechanisms and for the development of better strategies in the management and prevention of virus-related AECOPD.",2017 Mar 2,"['Zheng, Jingtong', 'Shi, Yue', 'Xiong, Lingxin', 'Zhang, Weijie', 'Li, Ying', 'Gibson, Peter G.', 'Simpson, Jodie L.', 'Zhang, Chao', 'Lu, Junying', 'Sai, Jingying', 'Wang, Guoqiang', 'Wang, Fang']",J Immunol Res,,,True
f50bc0f52caca340de8ba25900681253da739f2f,PMC,"Incidence, risk factors and clinical outcomes of acute kidney injury associated with scrub typhus: a retrospective study of 510 consecutive patients in South Korea (2001–2013)",http://dx.doi.org/10.1136/bmjopen-2016-013882,PMC5353335,28298367,CC BY,"OBJECTIVES: Renal involvement in scrub typhus ranges from simple urinary abnormalities to acute kidney injury (AKI) leading to death. This study evaluated the incidence, predictors and prognosis of AKI associated with scrub typhus according to the RIFLE (risk, injury, failure, loss, end-stage kidney disease) criteria. METHODS: We retrospectively evaluated the medical records of patients diagnosed with scrub typhus from January 2001 to November 2013 in Gyeongsang National University Hospital. RESULTS: During the study period, 510 patients were diagnosed with scrub typhus and the incidence of AKI was 35.9%. There were 132 (25.9%) patients at risk, 37 (7.3%) with injury and 14 (2.7%) with failure. In comparison with the non-AKI group, the AKI group was older (73.9 vs 63.4 years, p<0.001) and had more comorbidities such as hypertension, diabetes mellitus and chronic kidney disease (CKD). AKI frequently occurs in hypertensive patients taking angiotensin receptor blockers or ACE inhibitors (p=0.002), and in patients with diabetes with higher glycated haemoglobin levels (p=0.033). Haematuria and proteinuria were more frequent in the AKI group. There was no relationship between the severity of proteinuria and occurrence of AKI. Intensive care unit admission and death were more frequent in the AKI group. The renal function of most patients with AKI recovered without sequelae, except for 1 patient who had underlying CKD. Multivariate analysis showed that age, presence of CKD, serum albumin level and time to hospital presentation after symptom onset were independent predictors of AKI in patients with scrub typhus. CONCLUSIONS: Our current results suggest that the presence of underlying CKD, older age, lower serum albumin level and time to hospital presentation after symptom onset were important risk factors to determine occurrence of AKI. Whether earlier diagnosis and treatment in patients with the above risk factors reduce the incidence and severity of AKI deserves to be investigated.",2017 Mar 15,"['Hwang, Kyungo', 'Jang, Ha Nee', 'Lee, Tae Won', 'Cho, Hyun Seop', 'Bae, Eunjin', 'Chang, Se-Ho', 'Park, Dong Jun']",BMJ Open,,,True
19744eafb1b8520fa460274845713451ad539e91,PMC,Proteomics computational analyses suggest that the carboxyl terminal glycoproteins of Bunyaviruses are class II viral fusion protein (beta-penetrenes),http://dx.doi.org/10.1186/1742-4682-1-10,PMC535339,15544707,CC BY,"The Bunyaviridae family of enveloped RNA viruses includes five genuses, orthobunyaviruses, hantaviruses, phleboviruses, nairoviruses and tospoviruses. It has not been determined which Bunyavirus protein mediates virion:cell membrane fusion. Class II viral fusion proteins (beta-penetrenes), encoded by members of the Alphaviridae and Flaviviridae, are comprised of three antiparallel beta sheet domains with an internal fusion peptide located at the end of domain II. Proteomics computational analyses indicate that the carboxyl terminal glycoprotein (Gc) encoded by Sandfly fever virus (SAN), a phlebovirus, has a significant amino acid sequence similarity with envelope protein 1 (E1), the class II fusion protein of Sindbis virus (SIN), an Alphavirus. Similar sequences and common structural/functional motifs, including domains with a high propensity to interface with bilayer membranes, are located collinearly in SAN Gc and SIN E1. Gc encoded by members of each Bunyavirus genus share several sequence and structural motifs. These results suggest that Gc of Bunyaviridae, and similar proteins of Tenuiviruses and a group of Caenorhabditis elegans retroviruses, are class II viral fusion proteins. Comparisons of divergent viral fusion proteins can reveal features essential for virion:cell fusion, and suggest drug and vaccine strategies.",2004 Nov 15,"['Garry, Courtney E', 'Garry, Robert F']",Theor Biol Med Model,,,True
5d89d3273a8590afe87b37195d47f7e0c00d777c,PMC,A novel benzo-heterocyclic amine derivative N30 inhibits influenza virus replication by depression of Inosine-5’-Monophospate Dehydrogenase activity,http://dx.doi.org/10.1186/s12985-017-0724-6,PMC5353780,28298229,CC BY,"BACKGROUD: Influenza virus is still a huge threat to the world-wide public health. Host inosine-5’- monophosphate dehydrogenase (IMPDH) involved in the synthesis of guanine nucleotides, is known to be a potential target to inhibit the replication of viruses. Herein, we evaluated antiviral activity of a benzo-heterocyclic amine derivative N30, which was designed to inhibit IMPDH. RESULTS: The results demonstrated that N30 inhibited the replication of H1N1, H3N2, influenza B viruses, including oseltamivir and amantadine resistant strains in vitro. Mechanistically, neuraminidase inhibition assay and hemagglutination inhibition assay suggested that N30 did not directly target the two envelope glycoproteins required for viral adsorption or release. Instead, the compound could depress the activity of IMPDH type II. Based on these findings, we further confirmed that N30 provided a strong inhibition on the replication of respiratory syncytial virus, coronavirus, enterovirus 71 and a diverse strains of coxsackie B virus. CONCLUSIONS: We identified the small molecule N30, as an inhibitor of IMPDH, might be a potential candidate to inhibit the replication of various viruses.",2017 Mar 15,"['Hu, Jin', 'Ma, Linlin', 'Wang, Huiqiang', 'Yan, Haiyan', 'Zhang, Dajun', 'Li, Zhuorong', 'Jiang, Jiandong', 'Li, Yuhuan']",Virol J,,,True
77984a8d832663c5cd43e17e34a37470b3d95406,PMC,Human metapnuemovirus infections in hospitalized children and comparison with other respiratory viruses. 2005-2014 prospective study,http://dx.doi.org/10.1371/journal.pone.0173504,PMC5354294,28301570,CC BY,"BACKGROUND: Human metapneumovirus (HMPV) has an important etiological role in acute lower respiratory infections in children under five years. Our objectives were to estimate the relative contribution of HMPV to hospitalization in children with acute respiratory infection, to define the clinical and epidemiological features of HMPV single and multiple infections, and to compare HMPV infections with respiratory syncytial virus (HRSV), rhinovirus (HRV), adenovirus and human bocavirus infections in the same population. METHODS AND FINDINGS: A prospective study performed on all children less than 14 years of age with a respiratory tract disease admitted to a secondary hospital between September 2005- June 2014. Clinical characteristics of patients were analyzed. Nasopharyngeal aspirate was taken at admission for viral study with polymerase chain reaction for 16 respiratory viruses. A total of 3,906 children were included. At least one respiratory virus was detected in 75.2% of them. The most common identified virus was HRSV, followed by HRV. HMPV was detected in 214 cases (5.5%); 133 (62%) were single infections and the remaining were detected in coinfection with other viruses. 90.7% cases were detected between February and May. Children’s mean age was 13.83 ± 18 months. Fever was frequent (69%), and bronchiolitis (27%), and recurrent wheezing (63%) were the main clinical diagnosis. Hypoxia was present in 65% of the patients and 47% of them had an infiltrate in X-ray. Only 6 (2.8%) children were admitted to the intensive care unit. Only the duration of the hospitalization was different, being longer in the coinfections group (p <0.05). There were many differences in seasonality and clinical characteristics between HMPV and other respiratory viruses being more similar to HRSV. CONCLUSIONS: HMPV infections accounted for 5.5% of total viral infections in hospitalized children. The clinical characteristics were similar to HRSV infections, but seasonality and clinical data were different from other viral infections.",2017 Mar 16,"['García-García, María Luz', 'Calvo, Cristina', 'Rey, Cristina', 'Díaz, Beatriz', 'Molinero, Maria del Mar', 'Pozo, Francisco', 'Casas, Inmaculada']",PLoS One,,,True
e0cc48136126e2cae2d7ac3eb10a9fc786124404,PMC,Development of the full-length cDNA clones of two porcine epidemic diarrhea disease virus isolates with different virulence,http://dx.doi.org/10.1371/journal.pone.0173998,PMC5354467,28301551,CC BY,"The recently emerged highly virulent variants of porcine epidemic and diarrhea virus (PEDV) remain a huge threat to the worldwide swine industry. Here, we describe the development of a bacterial artificial chromosome (BAC) reverse genetics system for PEDV based on two recent Chinese field isolates, namely CHM2013 and BJ2011C. Phylogenetically, CHM2013 is closely related to the vaccine strain SM98 whereas the isolate BJ2011C belongs to the GIIb group, a cluster that contains many recent pandemic strains. The full-length cDNA clones of the two isolates were constructed into BAC under the control of CMV promoter. The rescued viruses rBJ2011C and rCHM2013 were found to replicate at the kinetics similar to their respective parental viruses in cell culture. When tested in the 2-day-old pig model, rBJ2011C caused severe diarrhea of piglets with extensive damages to the intestinal epithelium, leading to 100% fatality within 48 hours. In contrast, the rCHM2013-inoculated piglets all survived with only very minor tissue damage observed. Thus, we have successfully established a convenient platform for PEDV genome manipulation. This study also represents the first description of a DNA-launched reverse genetics system for the highly virulent PEDV.",2017 Mar 16,"['Li, Jie', 'Jin, Zhonghui', 'Gao, Yueyi', 'Zhou, Lei', 'Ge, Xinna', 'Guo, Xin', 'Han, Jun', 'Yang, Hanchun']",PLoS One,,,True
8c4450ec40a0642f9c28bb561ae210baacc032fa,PMC,Middle east respiratory syndrome corona virus spike glycoprotein suppresses macrophage responses via DPP4-mediated induction of IRAK-M and PPARγ,http://dx.doi.org/10.18632/oncotarget.14754,PMC5354714,28118607,CC BY,"Middle East Respiratory Syndrome Corona Virus (MERS-CoV) is transmitted via the respiratory tract and causes severe Acute Respiratory Distress Syndrome by infecting lung epithelial cells and macrophages. Macrophages can readily recognize the virus and eliminate it. MERS-CoV infects cells via its Spike (S) glycoprotein that binds on Dipeptidyl-Peptidase 4 (DPP4) receptor present on macrophages. Whether this Spike/DPP4 association affects macrophage responses remains unknown. Herein we demonstrated that infection of macrophages with lentiviral particles pseudotyped with MERS-CoV S glycoprotein results in suppression of macrophage responses since it reduced the capacity of macrophages to produce TNFa and IL-6 in naive and LPS-activated THP-1 macrophages and augmented LPS-induced production of the immunosuppressive cytokine IL-10. MERS-CoV S glycoprotein induced the expression of the negative regulator of TLR signaling IRAK-M as well as of the transcriptional repressor PPARγ. Inhibition of DPP4 by its inhibitor sitagliptin or siRNA abrogated the effects of MERS-CoV S glycoprotein on IRAK-M, PPARγ and IL-10, confirming that its immunosuppressive effects were mediated by DPP4 receptor. The effect was observed both in THP-1 macrophages and human primary peripheral blood monocytes. These findings support a DPP4-mediated suppressive action of MERS-CoV in macrophages and suggest a potential target for effective elimination of its pathogenicity.",2017 Jan 19,"['Al-Qahtani, Ahmed A.', 'Lyroni, Konstantina', 'Aznaourova, Marina', 'Tseliou, Melpomeni', 'Al-Anazi, Mashael R.', 'Al-Ahdal, Mohammed N.', 'Alkahtani, Saad', 'Sourvinos, George', 'Tsatsanis, Christos']",Oncotarget,,,True
0c5ba07b1db67c782e2c853283e1cadff2edd28a,PMC,Middle east respiratory syndrome corona virus spike glycoprotein suppresses macrophage responses via DPP4-mediated induction of IRAK-M and PPARγ,http://dx.doi.org/10.18632/oncotarget.14754,PMC5354714,28118607,CC BY,"Middle East Respiratory Syndrome Corona Virus (MERS-CoV) is transmitted via the respiratory tract and causes severe Acute Respiratory Distress Syndrome by infecting lung epithelial cells and macrophages. Macrophages can readily recognize the virus and eliminate it. MERS-CoV infects cells via its Spike (S) glycoprotein that binds on Dipeptidyl-Peptidase 4 (DPP4) receptor present on macrophages. Whether this Spike/DPP4 association affects macrophage responses remains unknown. Herein we demonstrated that infection of macrophages with lentiviral particles pseudotyped with MERS-CoV S glycoprotein results in suppression of macrophage responses since it reduced the capacity of macrophages to produce TNFa and IL-6 in naive and LPS-activated THP-1 macrophages and augmented LPS-induced production of the immunosuppressive cytokine IL-10. MERS-CoV S glycoprotein induced the expression of the negative regulator of TLR signaling IRAK-M as well as of the transcriptional repressor PPARγ. Inhibition of DPP4 by its inhibitor sitagliptin or siRNA abrogated the effects of MERS-CoV S glycoprotein on IRAK-M, PPARγ and IL-10, confirming that its immunosuppressive effects were mediated by DPP4 receptor. The effect was observed both in THP-1 macrophages and human primary peripheral blood monocytes. These findings support a DPP4-mediated suppressive action of MERS-CoV in macrophages and suggest a potential target for effective elimination of its pathogenicity.",2017 Jan 19,"['Al-Qahtani, Ahmed A.', 'Lyroni, Konstantina', 'Aznaourova, Marina', 'Tseliou, Melpomeni', 'Al-Anazi, Mashael R.', 'Al-Ahdal, Mohammed N.', 'Alkahtani, Saad', 'Sourvinos, George', 'Tsatsanis, Christos']",Oncotarget,,,False
7aec817203fd739cf21556a51e240c4cbbec5dc2,PMC,MERS-CoV virus-like particles produced in insect cells induce specific humoural and cellular imminity in rhesus macaques,http://dx.doi.org/10.18632/oncotarget.8475,PMC5355045,27050368,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease in humans with a case fatality rate of over 39%, and poses a considerable threat to public health. A lack of approved vaccine or drugs currently constitutes a roadblock in controlling disease outbreak and spread. In this study, we generated MERS-CoV VLPs using the baculovirus expression system. Electron microscopy and immunoelectron microscopy results demonstrate that MERS-CoV VLPs are structurally similar to the native virus. Rhesus macaques inoculated with MERS-CoV VLPs and Alum adjuvant induced virus-neutralizing antibodies titers up to 1:40 and induced specific IgG antibodies against the receptor binding domain (RBD), with endpoint titers reaching 1:1,280. MERS-CoV VLPs also elicited T-helper 1 cell (Th1)-mediated immunity, as measured by ELISpot. These data demonstrate that MERS-CoV VLPs have excellent immunogenicity in rhesus macaques, and represent a promising vaccine candidate.",2016 Mar 30,"['Wang, Chong', 'Zheng, Xuexing', 'Gai, Weiwei', 'Zhao, Yongkun', 'Wang, Hualei', 'Wang, Haijun', 'Feng, Na', 'Chi, Hang', 'Qiu, Boning', 'Li, Nan', 'Wang, Tiecheng', 'Gao, Yuwei', 'Yang, Songtao', 'Xia, Xianzhu']",Oncotarget,,,True
568917a765516d1397d8cb461644e755cd703c90,PMC,High TMPRSS11D protein expression predicts poor overall survival in non-small cell lung cancer,http://dx.doi.org/10.18632/oncotarget.14559,PMC5355057,28086212,CC BY,"TMPRSS11D (HAT) belongs to the large type II transmembrane serine protease (TTSP) family, participating in various biological and physiological processes. TMPRSS11D expression has been reported during squamous cell carcinogenesis, however, its expression during non-small cell lung cancer (NSCLC) development has not been studied. In this study, we determined the mRNA and protein expression of TMPRSS11D in NSCLC tumorous and matched adjacent normal tissues by quantitative reverse transcription PCR (qRT-PCR) and tissue microarray immunohistochemistry analysis (TMA-IHC) respectively. TMPRSS11D protein expression in tumorous tissues were correlated with NSCLC patients’ clinical characteristics and overall survival. Both TMPRSS11D mRNA and protein expression levels were significantly higher in NSCLC tumorous tissues than in adjacent normal tissues. High TMPRSS11D protein expression was associated with high TNM stages, and high TMPRSS11D protein expression is an independent prognostic marker in NSCLC. Based on our results, we conclude that TMPRSS11D could play a role in NSCLC development and progression. Because of its role in proteolysis of extracellular matrix, targeting TMPRSS11D may prevent the development of metastasis in NSCLC.",2017 Jan 9,"['Cao, Xiang', 'Tang, Zhiyuan', 'Huang, Fang', 'Jin, Qin', 'Zhou, Xiaoyu', 'Shi, Jiahai']",Oncotarget,,,True
bfd8dbd39a258f0a769375e64f7bd8df0e757266,PMC,Activating transcription factor 3 is crucial for antitumor activity and to strengthen the antiviral properties of Onconase,http://dx.doi.org/10.18632/oncotarget.14302,PMC5355296,28035074,CC BY,"Onconase is a ribonuclease that presents both antitumor and antiviral properties linked to its ribonucleolytic activity and represents a new class of RNA-damaging drugs. It has reached clinical trials for the treatment of several cancers and human papilloma virus warts. Onconase targets different RNAs in the cell cytosol but Onconase-treated cells present features that are different from a simple arrest of protein synthesis. We have used microarray-derived transcriptional profiling to identify Onconase-regulated genes in two ovarian cancer cell lines (NCI/ADR-RES and OVCAR-8). RT-qPCR analyses have confirmed the microarray findings. We have identified a network of up-regulated genes implicated in different signaling pathways that may explain the cytotoxic effects exerted by Onconase. Among these genes, activating transcription factor 3 (ATF3) plays a central role in the key events triggered by Onconase in treated cancer cells that finally lead to apoptosis. This mechanism, mediated by ATF3, is cell-type independent. Up-regulation of ATF3 may also explain the antiviral properties of this ribonuclease because this factor is involved in halting viral genome replication, keeping virus latency or preventing viral oncogenesis. Finally, Onconase-regulated genes are different from those affected by nuclear-directed ribonucleases.",2016 Dec 27,"['Vert, Anna', 'Castro, Jessica', 'Ribó, Marc', 'Benito, Antoni', 'Vilanova, Maria']",Oncotarget,,,True
2d3fa13b64865acb4b7e8ba9e1bd9c8621e5dd5d,PMC,Activating transcription factor 3 is crucial for antitumor activity and to strengthen the antiviral properties of Onconase,http://dx.doi.org/10.18632/oncotarget.14302,PMC5355296,28035074,CC BY,"Onconase is a ribonuclease that presents both antitumor and antiviral properties linked to its ribonucleolytic activity and represents a new class of RNA-damaging drugs. It has reached clinical trials for the treatment of several cancers and human papilloma virus warts. Onconase targets different RNAs in the cell cytosol but Onconase-treated cells present features that are different from a simple arrest of protein synthesis. We have used microarray-derived transcriptional profiling to identify Onconase-regulated genes in two ovarian cancer cell lines (NCI/ADR-RES and OVCAR-8). RT-qPCR analyses have confirmed the microarray findings. We have identified a network of up-regulated genes implicated in different signaling pathways that may explain the cytotoxic effects exerted by Onconase. Among these genes, activating transcription factor 3 (ATF3) plays a central role in the key events triggered by Onconase in treated cancer cells that finally lead to apoptosis. This mechanism, mediated by ATF3, is cell-type independent. Up-regulation of ATF3 may also explain the antiviral properties of this ribonuclease because this factor is involved in halting viral genome replication, keeping virus latency or preventing viral oncogenesis. Finally, Onconase-regulated genes are different from those affected by nuclear-directed ribonucleases.",2016 Dec 27,"['Vert, Anna', 'Castro, Jessica', 'Ribó, Marc', 'Benito, Antoni', 'Vilanova, Maria']",Oncotarget,,,False
2f5c3733e35cbcc1bb8c2eaded2796d59d94ff2a,PMC,FluMob: Enabling Surveillance of Acute Respiratory Infections in Health-care Workers via Mobile Phones,http://dx.doi.org/10.3389/fpubh.2017.00049,PMC5355489,28367433,CC BY,"Singapore is a hotspot for emerging infectious diseases and faces a constant risk of pandemic outbreaks as a major travel and health hub for Southeast Asia. With an increasing penetration of smart phone usage in this region, Singapore’s pandemic preparedness framework can be strengthened by applying a mobile-based approach to health surveillance and control, and improving upon existing ideas by addressing gaps, such as a lack of health communication. FluMob is a digitally integrated syndromic surveillance system designed to assist health authorities in obtaining real-time epidemiological and surveillance data from health-care workers (HCWs) within Singapore, by allowing them to report influenza incidence using smartphones. The system, integrating a fully responsive web-based interface and a mobile interface, is made available to HCW using various types of mobile devices and web browsers. Real-time data generated from FluMob will be complementary to current health-care- and laboratory-based systems. This paper describes the development of FluMob, as well as challenges faced in the creation of the system.",2017 Mar 17,"['Lwin, May Oo', 'Yung, Chee Fu', 'Yap, Peiling', 'Jayasundar, Karthikayen', 'Sheldenkar, Anita', 'Subasinghe, Kosala', 'Foo, Schubert', 'Jayasinghe, Udeepa Gayantha', 'Xu, Huarong', 'Chai, Siaw Ching', 'Kurlye, Ashwin', 'Chen, Jie', 'Ang, Brenda Sze Peng']",Front Public Health,,,True
5ae438eff01ac41a451ff26064c3346805d1c1dc,PMC,Respiratory DNA viruses are undetectable in nasopharyngeal secretions from adenotonsillectomized children,http://dx.doi.org/10.1371/journal.pone.0174188,PMC5357011,28306724,CC BY,"Respiratory viruses are frequently detected in association with chronic tonsillar hypertrophy in the absence of symptoms of acute respiratory infection (ARI). The present analysis was done in follow-up to a previous clinical study done by this same group. Nasopharyngeal washes (NPWs) were obtained from 83 of 120 individuals at variable times post adenotonsillectomy, in the absence of ARI symptoms. A look back at virus detection results in NPWs from the same 83 individuals at the time of tonsillectomy revealed that 73.5% (61/83) were positive for one or more viruses. The overall frequency of respiratory virus detection in post-tonsillectomy NPWs was 58.8%. Rhinovirus (RV) was the agent most frequently detected, in 38 of 83 subjects (45.8%), followed by enterovirus in 7 (8.4%), human metapneumovirus in 6 (7.2%), human respiratory syncytial virus in 3 (3.6%) and human coronavirus in 1 (1.2%). Remarkably, there was no detection of adenovirus (HAdV) or human bocavirus (HBoV) in asymptomatic individuals in follow-up of adenotonsillectomy. In keeping with persistence of respiratory DNA viruses in human tonsils, tonsillectomy significantly reduces asymptomatic shedding of HAdV and HBoV in NPWs.",2017 Mar 17,"['Martins, Ronaldo Bragança', 'Rocha, Lucas Penna', 'Prates, Mirela Moreira', 'Gagliardi, Talita Bianca', 'Biasoli, Balduino', 'Leite, Marcelo Junqueira', 'Buzatto, Guilherme', 'Hyppolito, Miguel Angelo', 'Aragon, Davi Casale', 'Tamashiro, Edwin', 'Valera, Fabiana Cardoso Pereira', 'Arruda, Eurico', 'Anselmo-Lima, Wilma Terezinha']",PLoS One,,,True
efd2525b3152b3e266de9cbe4493141f20f5c41b,PMC,Respiratory DNA viruses are undetectable in nasopharyngeal secretions from adenotonsillectomized children,http://dx.doi.org/10.1371/journal.pone.0174188,PMC5357011,28306724,CC BY,"Respiratory viruses are frequently detected in association with chronic tonsillar hypertrophy in the absence of symptoms of acute respiratory infection (ARI). The present analysis was done in follow-up to a previous clinical study done by this same group. Nasopharyngeal washes (NPWs) were obtained from 83 of 120 individuals at variable times post adenotonsillectomy, in the absence of ARI symptoms. A look back at virus detection results in NPWs from the same 83 individuals at the time of tonsillectomy revealed that 73.5% (61/83) were positive for one or more viruses. The overall frequency of respiratory virus detection in post-tonsillectomy NPWs was 58.8%. Rhinovirus (RV) was the agent most frequently detected, in 38 of 83 subjects (45.8%), followed by enterovirus in 7 (8.4%), human metapneumovirus in 6 (7.2%), human respiratory syncytial virus in 3 (3.6%) and human coronavirus in 1 (1.2%). Remarkably, there was no detection of adenovirus (HAdV) or human bocavirus (HBoV) in asymptomatic individuals in follow-up of adenotonsillectomy. In keeping with persistence of respiratory DNA viruses in human tonsils, tonsillectomy significantly reduces asymptomatic shedding of HAdV and HBoV in NPWs.",2017 Mar 17,"['Martins, Ronaldo Bragança', 'Rocha, Lucas Penna', 'Prates, Mirela Moreira', 'Gagliardi, Talita Bianca', 'Biasoli, Balduino', 'Leite, Marcelo Junqueira', 'Buzatto, Guilherme', 'Hyppolito, Miguel Angelo', 'Aragon, Davi Casale', 'Tamashiro, Edwin', 'Valera, Fabiana Cardoso Pereira', 'Arruda, Eurico', 'Anselmo-Lima, Wilma Terezinha']",PLoS One,,,False
eafa59c04760ccbc3bf79cbd3857a375ffecab8d,PMC,Respiratory DNA viruses are undetectable in nasopharyngeal secretions from adenotonsillectomized children,http://dx.doi.org/10.1371/journal.pone.0174188,PMC5357011,28306724,CC BY,"Respiratory viruses are frequently detected in association with chronic tonsillar hypertrophy in the absence of symptoms of acute respiratory infection (ARI). The present analysis was done in follow-up to a previous clinical study done by this same group. Nasopharyngeal washes (NPWs) were obtained from 83 of 120 individuals at variable times post adenotonsillectomy, in the absence of ARI symptoms. A look back at virus detection results in NPWs from the same 83 individuals at the time of tonsillectomy revealed that 73.5% (61/83) were positive for one or more viruses. The overall frequency of respiratory virus detection in post-tonsillectomy NPWs was 58.8%. Rhinovirus (RV) was the agent most frequently detected, in 38 of 83 subjects (45.8%), followed by enterovirus in 7 (8.4%), human metapneumovirus in 6 (7.2%), human respiratory syncytial virus in 3 (3.6%) and human coronavirus in 1 (1.2%). Remarkably, there was no detection of adenovirus (HAdV) or human bocavirus (HBoV) in asymptomatic individuals in follow-up of adenotonsillectomy. In keeping with persistence of respiratory DNA viruses in human tonsils, tonsillectomy significantly reduces asymptomatic shedding of HAdV and HBoV in NPWs.",2017 Mar 17,"['Martins, Ronaldo Bragança', 'Rocha, Lucas Penna', 'Prates, Mirela Moreira', 'Gagliardi, Talita Bianca', 'Biasoli, Balduino', 'Leite, Marcelo Junqueira', 'Buzatto, Guilherme', 'Hyppolito, Miguel Angelo', 'Aragon, Davi Casale', 'Tamashiro, Edwin', 'Valera, Fabiana Cardoso Pereira', 'Arruda, Eurico', 'Anselmo-Lima, Wilma Terezinha']",PLoS One,,,False
06ad398fdbe5c8c55aafb34013ff47b35f0cee35,PMC,Summarizing US Wildlife Trade with an Eye Toward Assessing the Risk of Infectious Disease Introduction,http://dx.doi.org/10.1007/s10393-017-1211-7,PMC5357285,28176029,CC BY,"The aim of this study was to characterize the role of the USA in the global exchange of wildlife and describe high volume trade with an eye toward prioritizing health risk assessment questions for further analysis. Here we summarize nearly 14 years (2000–2013) of the most comprehensive data available (USFWS LEMIS system), involving 11 billion individual specimens and an additional 977 million kilograms of wildlife. The majority of shipments contained mammals (27%), while the majority of specimens imported were shells (57%) and tropical fish (25%). Most imports were facilitated by the aquatic and pet industry, resulting in one-third of all shipments containing live animals. The importer reported origin of wildlife was 77.7% wild-caught and 17.7% captive-reared. Indonesia was the leading exporter of legal shipments, while Mexico was the leading source reported for illegal shipments. At the specimen level, China was the leading exporter of legal and illegal wildlife imports. The number of annual declared shipments doubled during the period examined, illustrating continually increasing demand, which reinforces the need to scale up capacity for border inspections, risk management protocols and disease surveillance. Most regulatory oversight of wildlife trade is aimed at conservation, rather than prevention of disease introduction.",2017 Feb 7,"['Smith, K. M.', 'Zambrana-Torrelio, C.', 'White, A.', 'Asmussen, M.', 'Machalaba, C.', 'Kennedy, S.', 'Lopez, K.', 'Wolf, T. M.', 'Daszak, P.', 'Travis, D. A.', 'Karesh, W. B.']",Ecohealth,,,True
92bda2372547fcfde4183483335747be9802976b,PMC,Secreted Interferon-Inducible Factors Restrict Hepatitis B and C Virus Entry In Vitro,http://dx.doi.org/10.1155/2017/4828936,PMC5358466,28367455,CC BY,"Interferon-α (IFN-α) has been used for more than 20 years as the first-line therapy for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, because it has a number of antiviral effects. In this study, we describe a novel mode of its antiviral action. We demonstrate that the supernatant from IFN-α-treated cultured cells restricted HBV and HCV infection by inhibiting viral entry into hepatoma cells. The factors contained in the supernatant competed with the virus for binding to heparan glycosaminoglycans—the nonspecific attachment step shared by HBV and HCV. Secreted factors of high molecular mass that bind to heparin columns elicited the antiviral effect. In conclusion, IFN-α is able to induce soluble factors that can bind to heparan glycosaminoglycans thus leading to the inhibition of viral binding.",2017 Mar 6,"['Xia, Yuchen', 'Cheng, Xiaoming', 'Blossey, Christoph K.', 'Wisskirchen, Karin', 'Esser, Knud', 'Protzer, Ulrike']",J Immunol Res,,,True
b39f328f57b886aeb4e596c69eee9fad32b8d3da,PMC,Re-imagining the future of diagnosis of Neglected Tropical Diseases,http://dx.doi.org/10.1016/j.csbj.2017.02.003,PMC5358522,28352456,CC BY,"Neglected Tropical Diseases (NTDs) affect an estimated 1 billion people in 149 countries. The World Health Organization (WHO) prioritised 17 NTDs for control and elimination by 2020 and defined a Road Map to help countries reach these goals. Improved diagnostics for NTDs are essential for guiding treatment strategies at different thresholds of control, interruption of transmission, elimination and post-elimination surveillance. While substantial progress has been made in the last decade with chemotherapy, the same cannot be said of diagnostics, largely due to the perceived lack of a commercially viable market for NTD diagnostics. New sample in-answer out nucleic acid amplification technologies that can be performed at the point-of-care offer improved performance over current technologies and the potential to test for multiple pathogens using a single specimen. Finding commonalities for different NTDs in terms of geographic overlap, sentinel populations and treatment strategy will allow NTD programs to leverage these innovations to build cost-effective multiplex surveillance platforms. Connectivity solutions linking data from diagnostic laboratories and POC test readers/devices provide opportunities for automated surveillance systems to make health systems more efficient, improving patient outcomes and assessing impact of interventions in real time. New models of public–private product development partnerships are critical in leveraging diagnostic innovation in other priority area for better diagnosis, control and elimination of NTDs.",2017 Feb 21,"['Peeling, Rosanna W.', 'Boeras, Debrah I.', 'Nkengasong, John']",Comput Struct Biotechnol J,,,False
f501b5ccc17158a3018dc5688b253e31ba0380d5,PMC,From protein-protein interactions to protein co-expression networks: a new perspective to evaluate large-scale proteomic data,http://dx.doi.org/10.1186/s13637-017-0059-z,PMC5359264,28477207,CC BY,"The reductionist approach of dissecting biological systems into their constituents has been successful in the first stage of the molecular biology to elucidate the chemical basis of several biological processes. This knowledge helped biologists to understand the complexity of the biological systems evidencing that most biological functions do not arise from individual molecules; thus, realizing that the emergent properties of the biological systems cannot be explained or be predicted by investigating individual molecules without taking into consideration their relations. Thanks to the improvement of the current -omics technologies and the increasing understanding of the molecular relationships, even more studies are evaluating the biological systems through approaches based on graph theory. Genomic and proteomic data are often combined with protein-protein interaction (PPI) networks whose structure is routinely analyzed by algorithms and tools to characterize hubs/bottlenecks and topological, functional, and disease modules. On the other hand, co-expression networks represent a complementary procedure that give the opportunity to evaluate at system level including organisms that lack information on PPIs. Based on these premises, we introduce the reader to the PPI and to the co-expression networks, including aspects of reconstruction and analysis. In particular, the new idea to evaluate large-scale proteomic data by means of co-expression networks will be discussed presenting some examples of application. Their use to infer biological knowledge will be shown, and a special attention will be devoted to the topological and module analysis.",2017 Mar 20,"['Vella, Danila', 'Zoppis, Italo', 'Mauri, Giancarlo', 'Mauri, Pierluigi', 'Di Silvestre, Dario']",EURASIP J Bioinform Syst Biol,,,True
d04f10a35adf7daa66ebda57b141ed79abac0a2c,PMC,Antibody-Dependent Cell-Mediated Cytotoxicity Epitopes on the Hemagglutinin Head Region of Pandemic H1N1 Influenza Virus Play Detrimental Roles in H1N1-Infected Mice,http://dx.doi.org/10.3389/fimmu.2017.00317,PMC5359280,28377769,CC BY,"Engaging the antibody-dependent cell-mediated cytotoxicity (ADCC) for killing of virus-infected cells and secretion of antiviral cytokines and chemokines was incorporated as one of the important features in the design of universal influenza vaccines. However, investigation of the ADCC epitopes on the highly immunogenic influenza hemagglutinin (HA) head region has been rarely reported. In this study, we determined the ADCC and antiviral activities of two putative ADCC epitopes, designated E1 and E2, on the HA head of a pandemic H1N1 influenza virus in vitro and in a lethal mouse model. Our data demonstrated that sera from the E1-vaccinated mice could induce high ADCC activities. Importantly, the induction of ADCC response modestly decreased viral load in the lungs of H1N1-infected mice. However, the elevated ADCC significantly increased mouse alveolar damage and mortality than that of the PBS-vaccinated group (P < 0.0001). The phenotype was potentially due to an exaggerated inflammatory cell infiltration triggered by ADCC, as an upregulated release of cytotoxic granules (perforin) was observed in the lung tissue of E1-vaccinated mice after H1N1 influenza virus challenge. Overall, our data suggested that ADCC elicited by certain domains of HA head region might have a detrimental rather than protective effect during influenza virus infection. Thus, future design of universal influenza vaccine shall strike a balance between the induction of protective immunity and potential side effects of ADCC.",2017 Mar 21,"['Ye, Zi-Wei', 'Yuan, Shuofeng', 'Poon, Kwok-Man', 'Wen, Lei', 'Yang, Dong', 'Sun, Zehua', 'Li, Cun', 'Hu, Meng', 'Shuai, Huiping', 'Zhou, Jie', 'Zhang, Mei-Yun', 'Zheng, Bo-Jian', 'Chu, Hin', 'Yuen, Kwok-Yung']",Front Immunol,,,True
ddd24c570c13a2251edc4e4251a5545ce215e935,PMC,"Meeting report: the 4(th) symposium on animal models of non-human primates in Kunming, Yunnan, China",http://dx.doi.org/10.13918/j.issn.2095-8137.2016.6.361,PMC5359324,28105801,CC BY,,2016 Nov 18,"['LI, Jia-Li', 'Shinn, CHOU', 'ZHENG, Yong-Tang', 'ZHAO, Xu-Dong', 'HU, Xin-Tian']",Zool Res,,,True
05e6e7a72d16a7294079af8e96f5d6b42d8ce51f,PMC,Multiplex Reverse-Transcription Loop-Mediated Isothermal Amplification Coupled with Cascade Invasive Reaction and Nanoparticle Hybridization for Subtyping of Influenza A Virus,http://dx.doi.org/10.1038/srep44924,PMC5359610,28322309,CC BY,"Considering the fatal human victims and economic loss caused by influenza virus infection every year, methodologies for rapid and on-site detection of influenza viruses are urgently needed. LAMP is the most commonly used nucleic acid isothermal amplification technology suitable for on-site use. However, for multiplex LAMP, differentiation of the amplicons derived from multiple targets is still challengeable currently. Here we developed a multiplex RT-LAMP assay for simultaneous amplification of three prominent subtypes of influenza viruses (A/H5, A/H7 and 2009A/H1). The amplicons were further identified by cascade invasive reaction and nanoparticle hybridization in separate target-specific detection tubes (referred to as mRT-LAMP-IRNH). The analytic sensitivities of the assay are 10 copies of RNA for all the three HA subtypes, and the specificity reached 100%. Clinical specimen analysis showed this assay had a combined sensitivity and specificity of 98.1% and 100%, respectively. Overall, the mRT-LAMP-IRNH assay can be used as a cost-saving method that utilizes a simple instrument to detect A/H5, A/H7, and 2009A/H1 influenza viruses, especially in resource-limited settings.",2017 Mar 21,"['Chi, Ying', 'Ge, Yiyue', 'Zhao, Kangchen', 'Zou, Bingjie', 'Liu, Bin', 'Qi, Xian', 'Bian, Qian', 'Shi, Zhiyang', 'Zhu, Fengcai', 'Zhou, Minghao', 'Cui, Lunbiao', 'Su, Chuan']",Sci Rep,,,True
170f0a7070650e42066d011135cc9e9d9f931223,PMC,Ecological niche modeling of rabies in the changing Arctic of Alaska,http://dx.doi.org/10.1186/s13028-017-0285-0,PMC5359834,28320440,CC BY,"BACKGROUND: Rabies is a disease of global significance including in the circumpolar Arctic. In Alaska enzootic rabies persist in northern and western coastal areas. Only sporadic cases have occurred in areas outside of the regions considered enzootic for the virus, such as the interior of the state and urbanized regions. RESULTS: Here we examine the distribution of diagnosed rabies cases in Alaska, explicit in space and time. We use a geographic information system (GIS), 20 environmental data layers and provide a quantitative non-parsimonious estimate of the predicted ecological niche, based on data mining, machine learning and open access data. We identify ecological correlates and possible drivers that determine the ecological niche of rabies virus in Alaska. More specifically, our models show that rabies cases are closely associated with human infrastructure, and reveal an ecological niche in remote northern wilderness areas. Furthermore a model utilizing climate modeling suggests a reduction of the current ecological niche for detection of rabies virus in Alaska, a state that is disproportionately affected by a changing climate. CONCLUSIONS: Our results may help to better inform public health decisions in the future and guide further studies on individual drivers of rabies distribution in the Arctic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-017-0285-0) contains supplementary material, which is available to authorized users.",2017 Mar 20,"['Huettmann, Falk', 'Magnuson, Emily Elizabeth', 'Hueffer, Karsten']",Acta Vet Scand,,,True
be815d7d57419bb6c21097290b83e5683b55c38d,PMC,Ecological niche modeling of rabies in the changing Arctic of Alaska,http://dx.doi.org/10.1186/s13028-017-0285-0,PMC5359834,28320440,CC BY,"BACKGROUND: Rabies is a disease of global significance including in the circumpolar Arctic. In Alaska enzootic rabies persist in northern and western coastal areas. Only sporadic cases have occurred in areas outside of the regions considered enzootic for the virus, such as the interior of the state and urbanized regions. RESULTS: Here we examine the distribution of diagnosed rabies cases in Alaska, explicit in space and time. We use a geographic information system (GIS), 20 environmental data layers and provide a quantitative non-parsimonious estimate of the predicted ecological niche, based on data mining, machine learning and open access data. We identify ecological correlates and possible drivers that determine the ecological niche of rabies virus in Alaska. More specifically, our models show that rabies cases are closely associated with human infrastructure, and reveal an ecological niche in remote northern wilderness areas. Furthermore a model utilizing climate modeling suggests a reduction of the current ecological niche for detection of rabies virus in Alaska, a state that is disproportionately affected by a changing climate. CONCLUSIONS: Our results may help to better inform public health decisions in the future and guide further studies on individual drivers of rabies distribution in the Arctic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-017-0285-0) contains supplementary material, which is available to authorized users.",2017 Mar 20,"['Huettmann, Falk', 'Magnuson, Emily Elizabeth', 'Hueffer, Karsten']",Acta Vet Scand,,,False
b454592972a3a296c30c336afe0287bbd5653e64,PMC,Ecological niche modeling of rabies in the changing Arctic of Alaska,http://dx.doi.org/10.1186/s13028-017-0285-0,PMC5359834,28320440,CC BY,"BACKGROUND: Rabies is a disease of global significance including in the circumpolar Arctic. In Alaska enzootic rabies persist in northern and western coastal areas. Only sporadic cases have occurred in areas outside of the regions considered enzootic for the virus, such as the interior of the state and urbanized regions. RESULTS: Here we examine the distribution of diagnosed rabies cases in Alaska, explicit in space and time. We use a geographic information system (GIS), 20 environmental data layers and provide a quantitative non-parsimonious estimate of the predicted ecological niche, based on data mining, machine learning and open access data. We identify ecological correlates and possible drivers that determine the ecological niche of rabies virus in Alaska. More specifically, our models show that rabies cases are closely associated with human infrastructure, and reveal an ecological niche in remote northern wilderness areas. Furthermore a model utilizing climate modeling suggests a reduction of the current ecological niche for detection of rabies virus in Alaska, a state that is disproportionately affected by a changing climate. CONCLUSIONS: Our results may help to better inform public health decisions in the future and guide further studies on individual drivers of rabies distribution in the Arctic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-017-0285-0) contains supplementary material, which is available to authorized users.",2017 Mar 20,"['Huettmann, Falk', 'Magnuson, Emily Elizabeth', 'Hueffer, Karsten']",Acta Vet Scand,,,False
abfbdc304e841cc0da2515ccc55e9fa1e7e93155,PMC,Ecological niche modeling of rabies in the changing Arctic of Alaska,http://dx.doi.org/10.1186/s13028-017-0285-0,PMC5359834,28320440,CC BY,"BACKGROUND: Rabies is a disease of global significance including in the circumpolar Arctic. In Alaska enzootic rabies persist in northern and western coastal areas. Only sporadic cases have occurred in areas outside of the regions considered enzootic for the virus, such as the interior of the state and urbanized regions. RESULTS: Here we examine the distribution of diagnosed rabies cases in Alaska, explicit in space and time. We use a geographic information system (GIS), 20 environmental data layers and provide a quantitative non-parsimonious estimate of the predicted ecological niche, based on data mining, machine learning and open access data. We identify ecological correlates and possible drivers that determine the ecological niche of rabies virus in Alaska. More specifically, our models show that rabies cases are closely associated with human infrastructure, and reveal an ecological niche in remote northern wilderness areas. Furthermore a model utilizing climate modeling suggests a reduction of the current ecological niche for detection of rabies virus in Alaska, a state that is disproportionately affected by a changing climate. CONCLUSIONS: Our results may help to better inform public health decisions in the future and guide further studies on individual drivers of rabies distribution in the Arctic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-017-0285-0) contains supplementary material, which is available to authorized users.",2017 Mar 20,"['Huettmann, Falk', 'Magnuson, Emily Elizabeth', 'Hueffer, Karsten']",Acta Vet Scand,,,False
35e064b054a771d099132d43c9ebb75cfee837b7,PMC,Ecological niche modeling of rabies in the changing Arctic of Alaska,http://dx.doi.org/10.1186/s13028-017-0285-0,PMC5359834,28320440,CC BY,"BACKGROUND: Rabies is a disease of global significance including in the circumpolar Arctic. In Alaska enzootic rabies persist in northern and western coastal areas. Only sporadic cases have occurred in areas outside of the regions considered enzootic for the virus, such as the interior of the state and urbanized regions. RESULTS: Here we examine the distribution of diagnosed rabies cases in Alaska, explicit in space and time. We use a geographic information system (GIS), 20 environmental data layers and provide a quantitative non-parsimonious estimate of the predicted ecological niche, based on data mining, machine learning and open access data. We identify ecological correlates and possible drivers that determine the ecological niche of rabies virus in Alaska. More specifically, our models show that rabies cases are closely associated with human infrastructure, and reveal an ecological niche in remote northern wilderness areas. Furthermore a model utilizing climate modeling suggests a reduction of the current ecological niche for detection of rabies virus in Alaska, a state that is disproportionately affected by a changing climate. CONCLUSIONS: Our results may help to better inform public health decisions in the future and guide further studies on individual drivers of rabies distribution in the Arctic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-017-0285-0) contains supplementary material, which is available to authorized users.",2017 Mar 20,"['Huettmann, Falk', 'Magnuson, Emily Elizabeth', 'Hueffer, Karsten']",Acta Vet Scand,,,True
5606419a7d2eba72813f2e1b85b12e823a6c4d36,PMC,"A career in a Kingdom: Journeys in infection, Mass Gathering Medicine and public health diplomacy",http://dx.doi.org/10.1080/21645515.2016.1226637,PMC5360126,27559845,CC BY,,2016 Aug 25,"Memish, Ziad",Hum Vaccin Immunother,,,False
ab2e4c7ae023d55fde4ae3df32825484d00fcb3f,PMC,GOST: A generic ordinal sequential trial design for a treatment trial in an emerging pandemic,http://dx.doi.org/10.1371/journal.pntd.0005439,PMC5360336,28278301,CC BY,"BACKGROUND: Conducting clinical trials to assess experimental treatments for potentially pandemic infectious diseases is challenging. Since many outbreaks of infectious diseases last only six to eight weeks, there is a need for trial designs that can be implemented rapidly in the face of uncertainty. Outbreaks are sudden and unpredictable and so it is essential that as much planning as possible takes place in advance. Statistical aspects of such trial designs should be evaluated and discussed in readiness for implementation. METHODOLOGY/PRINCIPAL FINDINGS: This paper proposes a generic ordinal sequential trial design (GOST) for a randomised clinical trial comparing an experimental treatment for an emerging infectious disease with standard care. The design is intended as an off-the-shelf, ready-to-use robust and flexible option. The primary endpoint is a categorisation of patient outcome according to an ordinal scale. A sequential approach is adopted, stopping as soon as it is clear that the experimental treatment has an advantage or that sufficient advantage is unlikely to be detected. The properties of the design are evaluated using large-sample theory and verified for moderate sized samples using simulation. The trial is powered to detect a generic clinically relevant difference: namely an odds ratio of 2 for better rather than worse outcomes. Total sample sizes (across both treatments) of between 150 and 300 patients prove to be adequate in many cases, but the precise value depends on both the magnitude of the treatment advantage and the nature of the ordinal scale. An advantage of the approach is that any erroneous assumptions made at the design stage about the proportion of patients falling into each outcome category have little effect on the error probabilities of the study, although they can lead to inaccurate forecasts of sample size. CONCLUSIONS/SIGNIFICANCE: It is important and feasible to pre-determine many of the statistical aspects of an efficient trial design in advance of a disease outbreak. The design can then be tailored to the specific disease under study once its nature is better understood.",2017 Mar 9,"['Whitehead, John', 'Horby, Peter']",PLoS Negl Trop Dis,,,True
295d1050a0d5e811698a853c29cc8b388d4d92f7,PMC,The Impact of the Interferon/TNF-Related Apoptosis-Inducing Ligand Signaling Axis on Disease Progression in Respiratory Viral Infection and Beyond,http://dx.doi.org/10.3389/fimmu.2017.00313,PMC5360710,28382038,CC BY,"Interferons (IFNs) are well described to be rapidly induced upon pathogen-associated pattern recognition. After binding to their respective IFN receptors and activation of the cellular JAK/signal transducer and activator of transcription signaling cascade, they stimulate the transcription of a plethora of IFN-stimulated genes (ISGs) in infected as well as bystander cells such as the non-infected epithelium and cells of the immune system. ISGs may directly act on the invading pathogen or can either positively or negatively regulate the innate and adaptive immune response. However, IFNs and ISGs do not only play a key role in the limitation of pathogen spread but have also been recently found to provoke an unbalanced, overshooting inflammatory response causing tissue injury and hampering repair processes. A prominent regulator of disease outcome, especially in—but not limited to—respiratory viral infection, is the IFN-dependent mediator TRAIL (TNF-related apoptosis-inducing ligand) produced by several cell types including immune cells such as macrophages or T cells. First described as an apoptosis-inducing agent in transformed cells, it is now also well established to rapidly evoke cellular stress pathways in epithelial cells, finally leading to caspase-dependent or -independent cell death. Hereby, pathogen spread is limited; however in some cases, also the surrounding tissue is severely harmed, thus augmenting disease severity. Interestingly, the lack of a strictly controlled and well balanced IFN/TRAIL signaling response has not only been implicated in viral infection but might furthermore be an important determinant of disease progression in bacterial superinfections and in chronic respiratory illness. Conclusively, the IFN/TRAIL signaling axis is subjected to a complex modulation and might be exploited for the evaluation of new therapeutic concepts aiming at attenuation of tissue injury.",2017 Mar 22,"['Peteranderl, Christin', 'Herold, Susanne']",Front Immunol,,,True
4800117f48b3a425e71f4271d450a1c07536765a,PMC,Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides,http://dx.doi.org/10.1038/srep43610,PMC5361215,28344321,CC BY,"Human paramyxoviruses include global causes of lower respiratory disease like the parainfluenza viruses, as well as agents of lethal encephalitis like Nipah virus. Infection is initiated by viral glycoprotein-mediated fusion between viral and host cell membranes. Paramyxovirus viral fusion proteins (F) insert into the target cell membrane, and form a transient intermediate that pulls the viral and cell membranes together as two heptad-repeat regions refold to form a six-helix bundle structure that can be specifically targeted by fusion-inhibitory peptides. Antiviral potency can be improved by sequence modification and lipid conjugation, and by adding linkers between the protein and lipid components. We exploit the uniquely broad spectrum antiviral activity of a parainfluenza F-derived peptide sequence that inhibits both parainfluenza and Nipah viruses, to investigate the influence of peptide orientation and intervening linker length on the peptides’ interaction with transitional states of F, solubility, membrane insertion kinetics, and protease sensitivity. We assessed the impact of these features on biodistribution and antiviral efficacy in vitro and in vivo. The engineering approach based on biophysical parameters resulted in a peptide that is a highly effective inhibitor of both paramyxoviruses and a set of criteria to be used for engineering broad spectrum antivirals for emerging paramyxoviruses.",2017 Mar 8,"['Mathieu, Cyrille', 'Augusto, Marcelo T.', 'Niewiesk, Stefan', 'Horvat, Branka', 'Palermo, Laura M.', 'Sanna, Giuseppina', 'Madeddu, Silvia', 'Huey, Devra', 'Castanho, Miguel A. R. B.', 'Porotto, Matteo', 'Santos, Nuno C.', 'Moscona, Anne']",Sci Rep,,,True
df6b70a2f62c9635377ece840d438d951d2558e5,PMC,The nasopharyngeal microbiota of beef cattle before and after transport to a feedlot,http://dx.doi.org/10.1186/s12866-017-0978-6,PMC5361731,28330466,CC BY,"BACKGROUND: The nasopharyngeal (NP) microbiota plays an important role in bovine health, comprising a rich and diverse microbial community. The nasopharynx is also the niche for potentially pathogenic agents which are associated with bovine respiratory disease (BRD), a serious and costly illness in feedlot cattle. We used 14 beef heifers from a closed and disease-free herd to assess the dynamics of the NP microbiota of cattle that are transported to a feedlot. Cattle were sampled prior to transport to the feedlot (day 0) and at days 2, 7, and 14. RESULTS: The structure of the NP microbiota changed significantly over the course of the study, with the largest shift occurring between day 0 (prior to transport) and day 2 (P < 0.001). Phylogenetic diversity and richness increased following feedlot placement (day 2; P < 0.05). The genera Pasteurella, Bacillus, and Proteus were enriched at day 0, Streptococcus and Acinetobacter at day 2, Bifidobacterium at day 7, and Mycoplasma at day 14. The functional potential of the NP microbiota was assessed using PICRUSt, revealing that replication and repair, as well as translation pathways, were more relatively abundant in day 14 samples. These differences were driven mostly by Mycoplasma. Although eight cattle were culture-positive for the BRD-associated bacterium Pasteurella multocida at one or more sampling times, none were culture-positive for Mannheimia haemolytica or Histophilus somni. CONCLUSIONS: This study investigated the effect that feedlot placement has on the NP microbiota of beef cattle over a 14-d period. Within two days of transport to the feedlot, the NP microbiota changed significantly, increasing in both phylogenetic diversity and richness. These results demonstrate that there is an abrupt shift in the NP microbiota of cattle after transportation to a feedlot. This may have importance for understanding why cattle are most susceptible to BRD after feedlot placement. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12866-017-0978-6) contains supplementary material, which is available to authorized users.",2017 Mar 22,"['Holman, Devin B.', 'Timsit, Edouard', 'Amat, Samat', 'Abbott, D. Wade', 'Buret, Andre G.', 'Alexander, Trevor W.']",BMC Microbiol,,,True
f8207b55dbdf90c353bda7975f849d94bd704653,PMC,Respiratory viruses in patients with influenza-like illness in Senegal: Focus on human respiratory adenoviruses,http://dx.doi.org/10.1371/journal.pone.0174287,PMC5362214,28328944,CC BY,"BACKGROUND: Human adenoviruses (HAdVs) are highly contagious pathogens that are associated with a wide spectrum of human illnesses involving the respiratory tract. In the present study, we investigate the epidemiologic and viral molecular features of HAdVs circulating in Senegal after 4 consecutive years of sentinel surveillance of influenza-like Illness cases. METHODOLOGY AND RESULTS: From January 2012 to December 2015 swabs were collected from consenting ILI outpatients. Adenoviral detection is performed by rRT-PCR with the Anyplex(™) II RV16 Detection kit (Seegene) and molecular characterization was performed using a partial hexon gene sequence. 6381 samples were collected. More than half of patients (51.7%; 3297/6381) were children of ≤ 5 years. 1967 (30.8%) were positive for HAdV with 1561 (79.4%) found in co-infection with at least one another respiratory virus. The most common co-detections were with influenza viruses (53.1%; 1045/1967), rhinoviruses (30%; 591/1967), enteroviruses (18.5%; 364/1967) and RSV (13.5%; 266/1967). Children under 5 were the most infected group (62.2%; 1224/1967; p <0.05). We noted that HAdV was detected throughout the year at a high level with detection peaks of different amplitudes without any clear seasonality. Phylogenetic analysis revealed species HAdV-C in majority, species HAdV-B and one HAdV- 4 genome type. The 9 HAdV-B species like strains from Senegal grouped with genome types HAdV-7, HAdV-55 and HAdV-11 as shown by a phylogenetic branch with a high bootstrap value of (88%). CONCLUSION: In conclusion, the results of the present study suggest strong year-round HAdV activity in Senegal, especially in children up to 5 years of age. Molecular studies revealed that the dominant species in circulation in patients with ILI appears to be HAdV-C and HAdV-B species. The circulation of though HAdV-7 and HAdV-55 genome types is of note as these serotypes are recognized causes of more severe and even fatal acute respiratory infections.",2017 Mar 22,"['Niang, Mbayame Ndiaye', 'Diop, Ndeye Sokhna', 'Fall, Amary', 'Kiori, Davy E.', 'Sarr, Fatoumata Diene', 'Sy, Sara', 'Goudiaby, Déborah', 'Barry, Mamadou Aliou', 'Fall, Malick', 'Dia, Ndongo']",PLoS One,,,True
df6c9f047f47069bc34b0b26c02aca2ab453f724,PMC,IκB-Kinase-epsilon (IKKε) over-expression promotes the growth of prostate cancer through the C/EBP-β dependent activation of IL-6 gene expression,http://dx.doi.org/10.18632/oncotarget.11629,PMC5362420,27577074,CC BY,"The inflammatory cytokine IL-6 has been shown to induce the nuclear translocation of androgen receptors in prostate cancer cells and to activate the androgen receptors in a ligand-independent manner, suggesting it may contribute to the development of a castrate-resistant phenotype. Elevated IL-6 serum levels have also been associated with metastasis-related morbidity in prostate cancer patients. We have previously established that over-expression of I-kappa-B-kinase-epsilon (IKKε also named IKKi or IκBKε) in hormone-sensitive prostate cancer cell lines induces IL-6 secretion. We have also reported that prostate cancer cell lines lacking androgen receptor expression exhibit high constitutive IKKε expression and IL-6 secretion. In the present study, we validated the impact of IKKε depletion on the in vitro proliferation of castrate-resistant prostate cancer cells, and characterized how IKKε depletion affects tumor growth and IL-6 tumor secretion in vivo through a mouse xenograft-based approach. We observed a significant growth delay in IKKε-silenced PC-3 cells injected in SCID mice fed with a doxycycline-supplemented diet in comparison with mice fed with a normal diet. We also found a decrease in IL-6 secretion levels that strongly correlated with tumor growth inhibition. Finally, using constructs with various IL-6-mutated promoters, we demonstrated that IKKε over-expression induces a NF-κB-independent stimulation of the IL-6 gene promoter through the activation and nuclear accumulation of the transcription factor C/EBP-β. Our study demonstrates the pro-proliferative role of the oncogene IKKε in castrate-resistant prostate cancer cell lines, involving the phosphorylation and nuclear translocation of C/EBP-β that initiates IL-6 gene expression.",2016 Aug 26,"['Péant, Benjamin', 'Gilbert, Sophie', 'Le Page, Cécile', 'Poisson, Alexis', 'L’Ecuyer, Emilie', 'Boudhraa, Zied', 'Bienz, Marc Nicolas', 'Delvoye, Nathalie', 'Saad, Fred', 'Mes-Masson, Anne-Marie']",Oncotarget,,,True
96d6226f5ae135097bd551040ec11ee91b333031,PMC,IκB-Kinase-epsilon (IKKε) over-expression promotes the growth of prostate cancer through the C/EBP-β dependent activation of IL-6 gene expression,http://dx.doi.org/10.18632/oncotarget.11629,PMC5362420,27577074,CC BY,"The inflammatory cytokine IL-6 has been shown to induce the nuclear translocation of androgen receptors in prostate cancer cells and to activate the androgen receptors in a ligand-independent manner, suggesting it may contribute to the development of a castrate-resistant phenotype. Elevated IL-6 serum levels have also been associated with metastasis-related morbidity in prostate cancer patients. We have previously established that over-expression of I-kappa-B-kinase-epsilon (IKKε also named IKKi or IκBKε) in hormone-sensitive prostate cancer cell lines induces IL-6 secretion. We have also reported that prostate cancer cell lines lacking androgen receptor expression exhibit high constitutive IKKε expression and IL-6 secretion. In the present study, we validated the impact of IKKε depletion on the in vitro proliferation of castrate-resistant prostate cancer cells, and characterized how IKKε depletion affects tumor growth and IL-6 tumor secretion in vivo through a mouse xenograft-based approach. We observed a significant growth delay in IKKε-silenced PC-3 cells injected in SCID mice fed with a doxycycline-supplemented diet in comparison with mice fed with a normal diet. We also found a decrease in IL-6 secretion levels that strongly correlated with tumor growth inhibition. Finally, using constructs with various IL-6-mutated promoters, we demonstrated that IKKε over-expression induces a NF-κB-independent stimulation of the IL-6 gene promoter through the activation and nuclear accumulation of the transcription factor C/EBP-β. Our study demonstrates the pro-proliferative role of the oncogene IKKε in castrate-resistant prostate cancer cell lines, involving the phosphorylation and nuclear translocation of C/EBP-β that initiates IL-6 gene expression.",2016 Aug 26,"['Péant, Benjamin', 'Gilbert, Sophie', 'Le Page, Cécile', 'Poisson, Alexis', 'L’Ecuyer, Emilie', 'Boudhraa, Zied', 'Bienz, Marc Nicolas', 'Delvoye, Nathalie', 'Saad, Fred', 'Mes-Masson, Anne-Marie']",Oncotarget,,,False
76418514384003ef87ee3e6922525db0b8bf0bd3,PMC,Immunogenicity of Candidate MERS-CoV DNA Vaccines Based on the Spike Protein,http://dx.doi.org/10.1038/srep44875,PMC5362948,28332568,CC BY,"MERS-coronavirus is a novel zoonotic pathogen which spread rapidly to >25 countries since 2012. Its apparent endemicity and the wide spread of its reservoir host (dromedary camels) in the Arabian Peninsula highlight the ongoing public health threat of this virus. Therefore, development of effective prophylactic vaccine needs to be urgently explored given that there are no approved prophylactics or therapeutics for humans or animals to date. Different vaccine candidates have been investigated but serious safety concerns remain over protein or full-length spike (S) protein-based vaccines. Here, we investigated the immunogenicity of naked DNA vaccines expressing different fragments of MERS-CoV S protein in mice. We found that plasmids expressing full-length (pS) or S1-subunit (pS1) could induce significant levels of S1-specific antibodies (Abs) but with distinct IgG isotype patterns. Specifically, pS1 immunization elicited a balanced Th1/Th2 response and generally higher levels of all IgG isotypes compared to pS vaccination. Interestingly, only mice immunized with pS1 demonstrated significant S1-specific cellular immune response. Importantly, both constructs induced cross-neutralizing Abs against multiple strains of human and camel origins. These results indicate that vaccines expressing S1-subunit of the MERS-CoV S protein could represent a potential vaccine candidate without the possible safety concerns associated with full-length protein-based vaccines.",2017 Mar 23,"['Al-amri, Sawsan S.', 'Abbas, Ayman T.', 'Siddiq, Loai A.', 'Alghamdi, Abrar', 'Sanki, Mohammad A.', 'Al-Muhanna, Muhanna K.', 'Alhabbab, Rowa Y.', 'Azhar, Esam I.', 'Li, Xuguang', 'Hashem, Anwar M.']",Sci Rep,,,True
fec29d4e9b94e386546a8e9474c4a357217f8eae,PMC,Immunogenicity of Candidate MERS-CoV DNA Vaccines Based on the Spike Protein,http://dx.doi.org/10.1038/srep44875,PMC5362948,28332568,CC BY,"MERS-coronavirus is a novel zoonotic pathogen which spread rapidly to >25 countries since 2012. Its apparent endemicity and the wide spread of its reservoir host (dromedary camels) in the Arabian Peninsula highlight the ongoing public health threat of this virus. Therefore, development of effective prophylactic vaccine needs to be urgently explored given that there are no approved prophylactics or therapeutics for humans or animals to date. Different vaccine candidates have been investigated but serious safety concerns remain over protein or full-length spike (S) protein-based vaccines. Here, we investigated the immunogenicity of naked DNA vaccines expressing different fragments of MERS-CoV S protein in mice. We found that plasmids expressing full-length (pS) or S1-subunit (pS1) could induce significant levels of S1-specific antibodies (Abs) but with distinct IgG isotype patterns. Specifically, pS1 immunization elicited a balanced Th1/Th2 response and generally higher levels of all IgG isotypes compared to pS vaccination. Interestingly, only mice immunized with pS1 demonstrated significant S1-specific cellular immune response. Importantly, both constructs induced cross-neutralizing Abs against multiple strains of human and camel origins. These results indicate that vaccines expressing S1-subunit of the MERS-CoV S protein could represent a potential vaccine candidate without the possible safety concerns associated with full-length protein-based vaccines.",2017 Mar 23,"['Al-amri, Sawsan S.', 'Abbas, Ayman T.', 'Siddiq, Loai A.', 'Alghamdi, Abrar', 'Sanki, Mohammad A.', 'Al-Muhanna, Muhanna K.', 'Alhabbab, Rowa Y.', 'Azhar, Esam I.', 'Li, Xuguang', 'Hashem, Anwar M.']",Sci Rep,,,False
fcededebc295dbf0fa5130e94002b7fe0a921f51,PMC,Temporal patterns and geographic heterogeneity of Zika virus (ZIKV) outbreaks in French Polynesia and Central America,http://dx.doi.org/10.7717/peerj.3015,PMC5363263,28344900,CC BY,"BACKGROUND: Zika virus (ZIKV) transmission has been reported in 67 countries/territories in the Oceania region and the Americas since 2015, prompting the World Health Organization (WHO) to declare ZIKV as a Public Health Emergency of International Concern in February 2016, due to its strong association with medical complications such as microcephaly and Guillain–Barré Syndrome (GBS). However, a substantial gap in knowledge still exists regarding differing temporal pattern and potential of transmission of ZIKV in different regions of the world. METHODS: We use a phenomenological model to ascertain the temporal patterns and transmission potential of ZIKV in various countries/territories, by fitting the model to Zika case data from Yap Island and French Polynesia in the Oceania region and 11 countries/territories with confirmed case data, namely, Colombia, Ecuador, French Guiana, Guadeloupe, Guatemala, Mexico, Nicaragua, Panama, Puerto Rico, Saint Martin, and Suriname, to pinpoint the waves of infections in each country/territory and to estimate the respective basic reproduction number R(0). RESULTS: Six of these time series datasets resulted in statistically significant model fit of at least one wave of reported cases, namely that of French Polynesia, Colombia, Puerto Rico, Guatemala, Suriname and Saint Martin. However, only Colombia and Guatemala exhibited two waves of cases while the others had only one wave. Temporal patterns of the second wave in Colombia and the single wave in Suriname are very similar, with the respective turning points separated by merely a week. Moreover, the mean estimates of R(0) for Colombia, Guatemala and Suriname, all land-based populations, range between 1.05 and 1.75, while the corresponding mean estimates for R(0) of island populations in French Polynesia, Puerto Rico and Saint Martin are significantly lower with a range of 5.70–6.89. We also fit the Richards model to Zika case data from six main archipelagos in French Polynesia, suggesting the outbreak in all six island populations occurred during the same time, albeit with different peak time, with mean R(0) range of 3.09–5.05. DISCUSSION: Using the same modeling methodology, in this study we found a significant difference between transmissibility (as quantified by R(0)) in island populations as opposed to land-based countries/territories, possibly suggesting an important role of geographic heterogeneity in the spread of vector-borne diseases and its future course, which requires further monitoring. Our result has potential implications for planning respective intervention and control policies targeted for island and land-based populations.",2017 Mar 21,"Hsieh, Ying-Hen",PeerJ,,,True
d359875ce36c09a5832bce1d508798496a5eae3a,PMC,ADAR1 and PACT contribute to efficient translation of transcripts containing HIV-1 trans-activating response (TAR) element,http://dx.doi.org/10.1042/BCJ20160964,PMC5363390,28167698,CC BY,"Human immunodeficiency virus type 1 (HIV-1) has evolved various measures to counter the host cell's innate antiviral response during the course of infection. Interferon (IFN)-stimulated gene products are produced following HIV-1 infection to limit viral replication, but viral proteins and RNAs counteract their effect. One such mechanism is specifically directed against the IFN-induced Protein Kinase PKR, which is centrally important to the cellular antiviral response. In the presence of viral RNAs, PKR is activated and phosphorylates the translation initiation factor eIF2α. This shuts down the synthesis of both host and viral proteins, allowing the cell to mount an effective antiviral response. PACT (protein activator of PKR) is a cellular protein activator of PKR, primarily functioning to activate PKR in response to cellular stress. Recent studies have indicated that during HIV-1 infection, PACT's normal cellular function is compromised and that PACT is unable to activate PKR. Using various reporter systems and in vitro kinase assays, we establish in this report that interactions between PACT, ADAR1 and HIV-1-encoded Tat protein diminish the activation of PKR in response to HIV-1 infection. Our results highlight an important pathway by which HIV-1 transcripts subvert the host cell's antiviral activities to enhance their translation.",2017 Apr 1,"['Chukwurah, Evelyn', 'Handy, Indhira', 'Patel, Rekha C.']",Biochem J,,,True
97e0348076235024d8bf38647c8db27abc7ffef2,PMC,Building the road to a regional zoonoses strategy: A survey of zoonoses programmes in the Americas,http://dx.doi.org/10.1371/journal.pone.0174175,PMC5363932,28333986,CC0,"BACKGROUND: In recent years, global public health security has been threatened by zoonotic disease emergence as exemplified by outbreaks of H5N1 and H1N1 influenza, SARS, and most recently Ebola and Zika. Additionally, endemic zoonoses, such as rabies, burden countries year after year, placing demands on limited finances and personnel. To survey the baseline status of the emerging and endemic zoonoses programmes of the Latin American and the Caribbean (LAC) countries, the Pan American Health Organization (PAHO) conducted a survey of priority emerging and endemic zoonoses, countries´ prioritization criteria and methodologies, and suggestions to strengthen countries capacities and regional approaches to zoonoses control. METHODS: A fillable online questionnaire was sent to the zoonoses programme managers of the Ministries of Health (MOH) and Ministries of Agriculture (MAg) of 33 LAC countries from January to April of 2015. The questionnaire comprised 36 single, multiple choice and open-ended questions to inform the objectives of the survey. A descriptive exploratory analysis was completed. RESULTS: Fifty-four ministries (26 MOH, 25 MAg, and 3 combined responses) in 31 LAC countries responded to the survey. Within the ministries, 22 (85%) MOH, 5 (20%) MAg, and 2 (67%) combined entities indicated they had specialized zoonoses units. For endemic zoonoses, 32 of 54 ministries responded that they conduct formal prioritization exercises, most of them annually (69%). The three priority endemic zoonoses for the MOHs were leptospirosis, rabies, and brucellosis while the three priorities for the MAgs were brucellosis, rabies, and tuberculosis. Diagnosis for rabies and leptospirosis were cited as the capacities most in need of development. The most needed cross-cutting capacity was coordination between stakeholders. For emerging zoonoses, 28 ministries performed formal prioritization exercises. The top prioritization criteria were probability of introduction into the country and impact. The three priority emerging zoonoses for the MOHs were Ebola viral disease, avian influenza, and Chikungunya while for the MAgs were avian influenza, bovine spongiform encephalopathy and West Nile virus disease. Surveillance for avian influenza and Ebola, and diagnosis for BSE were quoted as the capacities most needed. For all zoonoses, the majority of respondents (69%) ranked their relationship with the other Ministry as productive or very productive, and 31% minimally productive. Many countries requested a formal regional network, better regional communication and collaboration, and integrated surveillance. CONCLUSIONS: The survey is the first comprehensive effort to date to inform the status of zoonoses programmes in LAC. The information collected here will be used to develop a regional strategy for zoonoses (both endemic and emerging), increase efforts, advocacy, and promote prompt identification and management of EIDs and improvement of endemic programmes.",2017 Mar 23,"['Maxwell, Melody J.', 'Freire de Carvalho, Mary H.', 'Hoet, Armando E.', 'Vigilato, Marco A. N.', 'Pompei, Julio C.', 'Cosivi, Ottorino', 'del Rio Vilas, Victor J.']",PLoS One,,,True
375b438ae6250e39e16ed60349f924b2693f1d25,PMC,Building the road to a regional zoonoses strategy: A survey of zoonoses programmes in the Americas,http://dx.doi.org/10.1371/journal.pone.0174175,PMC5363932,28333986,CC0,"BACKGROUND: In recent years, global public health security has been threatened by zoonotic disease emergence as exemplified by outbreaks of H5N1 and H1N1 influenza, SARS, and most recently Ebola and Zika. Additionally, endemic zoonoses, such as rabies, burden countries year after year, placing demands on limited finances and personnel. To survey the baseline status of the emerging and endemic zoonoses programmes of the Latin American and the Caribbean (LAC) countries, the Pan American Health Organization (PAHO) conducted a survey of priority emerging and endemic zoonoses, countries´ prioritization criteria and methodologies, and suggestions to strengthen countries capacities and regional approaches to zoonoses control. METHODS: A fillable online questionnaire was sent to the zoonoses programme managers of the Ministries of Health (MOH) and Ministries of Agriculture (MAg) of 33 LAC countries from January to April of 2015. The questionnaire comprised 36 single, multiple choice and open-ended questions to inform the objectives of the survey. A descriptive exploratory analysis was completed. RESULTS: Fifty-four ministries (26 MOH, 25 MAg, and 3 combined responses) in 31 LAC countries responded to the survey. Within the ministries, 22 (85%) MOH, 5 (20%) MAg, and 2 (67%) combined entities indicated they had specialized zoonoses units. For endemic zoonoses, 32 of 54 ministries responded that they conduct formal prioritization exercises, most of them annually (69%). The three priority endemic zoonoses for the MOHs were leptospirosis, rabies, and brucellosis while the three priorities for the MAgs were brucellosis, rabies, and tuberculosis. Diagnosis for rabies and leptospirosis were cited as the capacities most in need of development. The most needed cross-cutting capacity was coordination between stakeholders. For emerging zoonoses, 28 ministries performed formal prioritization exercises. The top prioritization criteria were probability of introduction into the country and impact. The three priority emerging zoonoses for the MOHs were Ebola viral disease, avian influenza, and Chikungunya while for the MAgs were avian influenza, bovine spongiform encephalopathy and West Nile virus disease. Surveillance for avian influenza and Ebola, and diagnosis for BSE were quoted as the capacities most needed. For all zoonoses, the majority of respondents (69%) ranked their relationship with the other Ministry as productive or very productive, and 31% minimally productive. Many countries requested a formal regional network, better regional communication and collaboration, and integrated surveillance. CONCLUSIONS: The survey is the first comprehensive effort to date to inform the status of zoonoses programmes in LAC. The information collected here will be used to develop a regional strategy for zoonoses (both endemic and emerging), increase efforts, advocacy, and promote prompt identification and management of EIDs and improvement of endemic programmes.",2017 Mar 23,"['Maxwell, Melody J.', 'Freire de Carvalho, Mary H.', 'Hoet, Armando E.', 'Vigilato, Marco A. N.', 'Pompei, Julio C.', 'Cosivi, Ottorino', 'del Rio Vilas, Victor J.']",PLoS One,,,True
c0fcd483132e1e59571bae716303dc7d3977b7d6,PMC,The cellular protein hnRNP A2/B1 enhances HIV-1 transcription by unfolding LTR promoter G-quadruplexes,http://dx.doi.org/10.1038/srep45244,PMC5364415,28338097,CC BY,"G-quadruplexes are four-stranded conformations of nucleic acids that act as cellular epigenetic regulators. A dynamic G-quadruplex forming region in the HIV-1 LTR promoter represses HIV-1 transcription when in the folded conformation. This activity is enhanced by nucleolin, which induces and stabilizes the HIV-1 LTR G-quadruplexes. In this work by a combined pull-down/mass spectrometry approach, we consistently found hnRNP A2/B1 as an additional LTR-G-quadruplex interacting protein. Surface plasmon resonance confirmed G-quadruplex specificity over linear sequences and fluorescence resonance energy transfer analysis indicated that hnRNP A2/B1 is able to efficiently unfold the LTR G-quadruplexes. Evaluation of the thermal stability of the LTR G-quadruplexes in different-length oligonucleotides showed that the protein is fit to be most active in the LTR full-length environment. When hnRNP A2/B1 was silenced in cells, LTR activity decreased, indicating that the protein acts as a HIV-1 transcription activator. Our data highlight a tightly regulated control of transcription based on G-quadruplex folding/unfolding, which depends on interacting cellular proteins. These findings provide a deeper understanding of the viral transcription mechanism and may pave the way to the development of drugs effective against the integrated HIV-1, present both in actively and latently infected cells.",2017 Mar 24,"['Scalabrin, Matteo', 'Frasson, Ilaria', 'Ruggiero, Emanuela', 'Perrone, Rosalba', 'Tosoni, Elena', 'Lago, Sara', 'Tassinari, Martina', 'Palù, Giorgio', 'Richter, Sara N.']",Sci Rep,,,True
38d5edc7646419a23ace691d554549f622f5c8f0,PMC,The cellular protein hnRNP A2/B1 enhances HIV-1 transcription by unfolding LTR promoter G-quadruplexes,http://dx.doi.org/10.1038/srep45244,PMC5364415,28338097,CC BY,"G-quadruplexes are four-stranded conformations of nucleic acids that act as cellular epigenetic regulators. A dynamic G-quadruplex forming region in the HIV-1 LTR promoter represses HIV-1 transcription when in the folded conformation. This activity is enhanced by nucleolin, which induces and stabilizes the HIV-1 LTR G-quadruplexes. In this work by a combined pull-down/mass spectrometry approach, we consistently found hnRNP A2/B1 as an additional LTR-G-quadruplex interacting protein. Surface plasmon resonance confirmed G-quadruplex specificity over linear sequences and fluorescence resonance energy transfer analysis indicated that hnRNP A2/B1 is able to efficiently unfold the LTR G-quadruplexes. Evaluation of the thermal stability of the LTR G-quadruplexes in different-length oligonucleotides showed that the protein is fit to be most active in the LTR full-length environment. When hnRNP A2/B1 was silenced in cells, LTR activity decreased, indicating that the protein acts as a HIV-1 transcription activator. Our data highlight a tightly regulated control of transcription based on G-quadruplex folding/unfolding, which depends on interacting cellular proteins. These findings provide a deeper understanding of the viral transcription mechanism and may pave the way to the development of drugs effective against the integrated HIV-1, present both in actively and latently infected cells.",2017 Mar 24,"['Scalabrin, Matteo', 'Frasson, Ilaria', 'Ruggiero, Emanuela', 'Perrone, Rosalba', 'Tosoni, Elena', 'Lago, Sara', 'Tassinari, Martina', 'Palù, Giorgio', 'Richter, Sara N.']",Sci Rep,,,False
c96d197b59d78b7d5dba68fb9a4e5ef67bd066d1,PMC,"Identification of IFITM1 and IFITM3 in Goose: Gene Structure, Expression Patterns, and Immune Reponses against Tembusu Virus Infection",http://dx.doi.org/10.1155/2017/5149062,PMC5366768,28386554,CC BY,"As interferon-stimulated genes (ISGs), interferon-inducible transmembrane proteins 1 and 3 (IFITM1 and IFITM3) can effectively inhibit the replication of multiple viruses. Here, goose IFITM1 and IFITM3 were cloned and identified for the first time. The two proteins share the same topological structure and several important sites critical for the antiviral functions in other species are conserved in the goose. Goose IFITM1 and IFITM3 are most closely related to their respective orthologs in ducks; these proteins exhibited high mRNA transcript levels in immune-related tissues, including the thymus, bursa of Fabricius, and Harderian gland, compared to other tissues. Moreover, goose IFITM1 was highly constitutively expressed in gastrointestinal tract tissues, while goose IFITM3 was expressed in respiratory organs. Furthermore, goose IFITM3 was activated in goose peripheral blood mononuclear cells (PBMCs) infected with Tembusu virus (TMUV) or treated with Toll-like receptors (TLRs) agonists, while only the R848 and Poly (I:C) agonists induced significant upregulation of goose IFITM1. Furthermore, goose IFITM1 and IFITM3 were upregulated in the sampled tissues, to some extent, after TMUV infection. Notably, significant upregulation of goose IFITM1 and IFITM3 was detected in the cecum and cecal tonsil, where TMUV was primarily distributed. These data provide new insights into the immune effectors in geese and promote our understanding of the role of IFITM1 and IFITM3 in the defense against TMUV.",2017 Mar 13,"['Wang, Anqi', 'Sun, Lipei', 'Wang, Mingshu', 'Jia, Renyong', 'Zhu, Dekang', 'Liu, Mafeng', 'Sun, Kunfeng', 'Yang, Qiao', 'Wu, Ying', 'Chen, Xiaoyue', 'Cheng, Anchun', 'Chen, Shun']",Biomed Res Int,,,True
3654aa0ea8709bb844a9dd36d67c4e5d89ba3c83,PMC,Influenza A virus hemagglutinin and neuraminidase act as novel motile machinery,http://dx.doi.org/10.1038/srep45043,PMC5366856,28344335,CC BY,"Influenza A virus (IAV) membrane proteins hemagglutinin (HA) and neuraminidase (NA) are determinants of virus infectivity, transmissibility, pathogenicity, host specificity, and major antigenicity. HA binds to a virus receptor, a sialoglycoprotein or sialoglycolipid, on the host cell and mediates virus attachment to the cell surface. The hydrolytic enzyme NA cleaves sialic acid from viral receptors and accelerates the release of progeny virus from host cells. In this study, we identified a novel function of HA and NA as machinery for viral motility. HAs exchanged binding partner receptors iteratively, generating virus movement on a receptor-coated glass surface instead of a cell surface. The virus movement was also dependent on NA. Virus movement mediated by HA and NA resulted in a three to four-fold increase in virus internalisation by cultured cells. We concluded that cooperation of HA and NA moves IAV particles on a cell surface and enhances virus infection of host cells.",2017 Mar 27,"['Sakai, Tatsuya', 'Nishimura, Shin I.', 'Naito, Tadasuke', 'Saito, Mineki']",Sci Rep,,,True
35dc5a138c55a86477ff368b5f8a1faa4f05d2d7,PMC,Influenza A virus hemagglutinin and neuraminidase act as novel motile machinery,http://dx.doi.org/10.1038/srep45043,PMC5366856,28344335,CC BY,"Influenza A virus (IAV) membrane proteins hemagglutinin (HA) and neuraminidase (NA) are determinants of virus infectivity, transmissibility, pathogenicity, host specificity, and major antigenicity. HA binds to a virus receptor, a sialoglycoprotein or sialoglycolipid, on the host cell and mediates virus attachment to the cell surface. The hydrolytic enzyme NA cleaves sialic acid from viral receptors and accelerates the release of progeny virus from host cells. In this study, we identified a novel function of HA and NA as machinery for viral motility. HAs exchanged binding partner receptors iteratively, generating virus movement on a receptor-coated glass surface instead of a cell surface. The virus movement was also dependent on NA. Virus movement mediated by HA and NA resulted in a three to four-fold increase in virus internalisation by cultured cells. We concluded that cooperation of HA and NA moves IAV particles on a cell surface and enhances virus infection of host cells.",2017 Mar 27,"['Sakai, Tatsuya', 'Nishimura, Shin I.', 'Naito, Tadasuke', 'Saito, Mineki']",Sci Rep,,,False
c95aaaeafc4bea827a28f4f300ca76608fecd107,PMC,Bacterial and viral pathogen spectra of acute respiratory infections in under-5 children in hospital settings in Dhaka city,http://dx.doi.org/10.1371/journal.pone.0174488,PMC5367831,28346512,CC BY,"The study aimed to examine for the first time the spectra of viral and bacterial pathogens along with the antibiotic susceptibility of the isolated bacteria in under-5 children with acute respiratory infections (ARIs) in hospital settings of Dhaka, Bangladesh. Nasal swabs were collected from 200 under-five children hospitalized with clinical signs of ARIs. Nasal swabs from 30 asymptomatic children were also collected. Screening of viral pathogens targeted ten respiratory viruses using RT-qPCR. Bacterial pathogens were identified by bacteriological culture methods and antimicrobial susceptibility of the isolates was determined following CLSI guidelines. About 82.5% (n = 165) of specimens were positive for pathogens. Of 165 infected cases, 3% (n = 6) had only single bacterial pathogens, whereas 43.5% (n = 87) cases had only single viral pathogens. The remaining 36% (n = 72) cases had coinfections. In symptomatic cases, human rhinovirus was detected as the predominant virus (31.5%), followed by RSV (31%), HMPV (13%), HBoV (11%), HPIV-3 (10.5%), and adenovirus (7%). Streptococcus pneumoniae was the most frequently isolated bacterial pathogen (9%), whereas Klebsiella pneumaniae, Streptococcus spp., Enterobacter agglomerans, and Haemophilus influenzae were 5.5%, 5%, 2%, and 1.5%, respectively. Of 15 multidrug-resistant bacteria, a Klebsiella pneumoniae isolate and an Enterobacter agglomerans isolate exhibited resistance against more than 10 different antibiotics. Both ARI incidence and predominant pathogen detection rates were higher during post-monsoon and winter, peaking in September. Pathogen detection rates and coinfection incidence in less than 1-year group were significantly higher (P = 0.0034 and 0.049, respectively) than in 1–5 years age group. Pathogen detection rate (43%) in asymptomatic cases was significantly lower compared to symptomatic group (P<0.0001). Human rhinovirus, HPIV-3, adenovirus, Streptococcus pneumonia, and Klebsiella pneumaniae had significant involvement in coinfections with P values of 0.0001, 0.009 and 0.0001, 0.0001 and 0.001 respectively. Further investigations are required to better understand the clinical roles of the isolated pathogens and their seasonality.",2017 Mar 27,"['Bhuyan, Golam Sarower', 'Hossain, Mohammad Amir', 'Sarker, Suprovath Kumar', 'Rahat, Asifuzzaman', 'Islam, Md Tarikul', 'Haque, Tanjina Noor', 'Begum, Noorjahan', 'Qadri, Syeda Kashfi', 'Muraduzzaman, A. K. M.', 'Islam, Nafisa Nawal', 'Islam, Mohammad Sazzadul', 'Sultana, Nusrat', 'Jony, Manjur Hossain Khan', 'Khanam, Farhana', 'Mowla, Golam', 'Matin, Abdul', 'Begum, Firoza', 'Shirin, Tahmina', 'Ahmed, Dilruba', 'Saha, Narayan', 'Qadri, Firdausi', 'Mannoor, Kaiissar']",PLoS One,,,True
5a6e220c6796a02e36a272103dd39dd62c9311eb,PMC,Antibody Engineering for Pursuing a Healthier Future,http://dx.doi.org/10.3389/fmicb.2017.00495,PMC5368232,28400756,CC BY,"Since the development of antibody-production techniques, a number of immunoglobulins have been developed on a large scale using conventional methods. Hybridoma technology opened a new horizon in the production of antibodies against target antigens of infectious pathogens, malignant diseases including autoimmune disorders, and numerous potent toxins. However, these clinical humanized or chimeric murine antibodies have several limitations and complexities. Therefore, to overcome these difficulties, recent advances in genetic engineering techniques and phage display technique have allowed the production of highly specific recombinant antibodies. These engineered antibodies have been constructed in the hunt for novel therapeutic drugs equipped with enhanced immunoprotective abilities, such as engaging immune effector functions, effective development of fusion proteins, efficient tumor and tissue penetration, and high-affinity antibodies directed against conserved targets. Advanced antibody engineering techniques have extensive applications in the fields of immunology, biotechnology, diagnostics, and therapeutic medicines. However, there is limited knowledge regarding dynamic antibody development approaches. Therefore, this review extends beyond our understanding of conventional polyclonal and monoclonal antibodies. Furthermore, recent advances in antibody engineering techniques together with antibody fragments, display technologies, immunomodulation, and broad applications of antibodies are discussed to enhance innovative antibody production in pursuit of a healthier future for humans.",2017 Mar 28,"['Saeed, Abdullah F. U. H.', 'Wang, Rongzhi', 'Ling, Sumei', 'Wang, Shihua']",Front Microbiol,,,True
e1c8f343e712b43a4cedc0a09731ceada6abc146,PMC,Does mRNA structure contain genetic information for regulating co-translational protein folding?,http://dx.doi.org/10.13918/j.issn.2095-8137.2017.004,PMC5368379,28271668,CC BY,"Currently many facets of genetic information are illdefined. In particular, how protein folding is genetically regulated has been a long-standing issue for genetics and protein biology. And a generic mechanistic model with supports of genomic data is still lacking. Recent technological advances have enabled much needed genome-wide experiments. While putting the effect of codon optimality on debate, these studies have supplied mounting evidence suggesting a role of mRNA structure in the regulation of protein folding by modulating translational elongation rate. In conjunctions with previous theories, this mechanistic model of protein folding guided by mRNA structure shall expand our understandings of genetic information and offer new insights into various biomedical puzzles.",2017 Jan 18,"Yang, Jian-Rong",Zool Res,,,True
aebf3e6b69b0563ab38d9d973db9a7795f75f47e,PMC,Simultaneous detection of respiratory syncytial virus and human metapneumovirus by one-step multiplex real-time RT-PCR in patients with respiratory symptoms,http://dx.doi.org/10.1186/s12887-017-0843-7,PMC5368990,28347279,CC BY,"BACKGROUND: Both respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are important viral pathogens causing respiratory tract infection (RTI) in the pediatric population. However, the clinical manifestations of RSV and hMPV infections are similar. Therefore, a reliable and rapid diagnostic tool is needed for diagnostic performance. METHODS: In order to optimize diagnosis efficiency of RTI, the aim of this study is to establish a rapid and advanced method for simultaneous detecting RSV and hMPV in nasopharyngeal aspirates specimens from patients. We designed a one-step triplex real-time RT-PCR (qRT-PCR) protocol using TaqMan probes for detecting RSV and hMPV. The plasmid clones containing RSV nucleoprotein gene and hMPV fusion gene were established as reference standards. We used virus culture supernatants from 86 known pediatric RTI patient to test the specificity and sensitivity of our assay. Then we used total 222 nasopharyngeal aspirates specimens from pediatric patients hospitalized with respiratory symptoms to evaluate our assay. RESULTS: Our one-step triplex qRT-PCR assay showed 100% sensitivity and specificity in testing RSV and hMPV in 86 known virus culture supernatants, with excellent linearity (R(2) > 0.99) and reliable reproducibility (CV lower than 1.04%). This assay has a wide dynamic range 10(2)-10(9)copies/reaction (limit of detection; LOD = 100 copies/reaction). A total of 222 patients hospitalized with respiratory symptoms were enrolled for clinical evaluation. In these samples, our qRT-PCR assay detected 68 RSV positive and 18 hMPV positive cases. However, standard virus culture only detected 8 RSV positive cases and 0 hMPV cases. Based on this improved triplex qRT-PCR assay, we found that RSV infection was associated with severe inflammation by chest X-ray and occurrence of pneumonia which were not observed previously. CONCLUSIONS: In summary, we have developed a highly specific and sensitive one-step triplex qRT-PCR assay to detect hMPV and RSV simultaneously. This assay offers a valuable tool for routine diagnosis.",2017 Mar 27,"['You, Huey-Ling', 'Chang, Shun-Jen', 'Yu, Hong-Ren', 'Li, Chia-Chin', 'Chen, Chang-Han', 'Liao, Wei-Ting']",BMC Pediatr,,,True
14597dad9c71c07579c0a5e5e9878aa1c003f50e,PMC,"Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses",http://dx.doi.org/10.3390/ijerph14030263,PMC5369099,28273867,CC BY,"This study aimed to assess the mortality risks for human infection with high (HPAI) and low (LPAI) pathogenicity avian influenza viruses. The HPAI case fatality rate (CFR) was far higher than the LPAI CFR [66.0% (293/444) vs. 68.75% (11/16) vs. 40.4% (265/656) vs. 0.0% (0/18) in the cases with H5N1, H5N6, H7N9, and H9N2 viruses, respectively; p < 0.001]. Similarly, the CFR of the index cases was greater than the secondary cases with H5N1 [100% (43/43) vs. 43.3% (42/97), p < 0.001]. Old age [22.5 vs. 17 years for H5N1, p = 0.018; 61 vs. 49 years for H7H9, p < 0.001], concurrent diseases [18.8% (15/80) vs. 8.33% (9/108) for H5N1, p = 0.046; 58.6% (156/266) vs. 34.8% (135/388) for H7H9, p < 0.001], delayed confirmation [13 vs. 6 days for H5N1, p < 0.001; 10 vs. 8 days for H7N9, p = 0.011] in the fatalities and survivors, were risk factors for deaths. With regard to the H5N1 clusters, exposure to poultry [67.4% (29/43) vs. 45.2% (19/42), p = 0.039] was the higher risk for the primary than the secondary deaths. In conclusion, old age, comorbidities, delayed confirmation, along with poultry exposure are the major risks contributing to fatal outcomes in human HPAI and LPAI infections.",2017 Mar 4,"['Wu, Zu-Qun', 'Zhang, Yi', 'Zhao, Na', 'Yu, Zhao', 'Pan, Hao', 'Chan, Ta-Chien', 'Zhang, Zhi-Ruo', 'Liu, She-Lan']",Int J Environ Res Public Health,,,True
d55dfd7d053d9bcdee4b5013a7fb8778c8593d66,PMC,"Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses",http://dx.doi.org/10.3390/ijerph14030263,PMC5369099,28273867,CC BY,"This study aimed to assess the mortality risks for human infection with high (HPAI) and low (LPAI) pathogenicity avian influenza viruses. The HPAI case fatality rate (CFR) was far higher than the LPAI CFR [66.0% (293/444) vs. 68.75% (11/16) vs. 40.4% (265/656) vs. 0.0% (0/18) in the cases with H5N1, H5N6, H7N9, and H9N2 viruses, respectively; p < 0.001]. Similarly, the CFR of the index cases was greater than the secondary cases with H5N1 [100% (43/43) vs. 43.3% (42/97), p < 0.001]. Old age [22.5 vs. 17 years for H5N1, p = 0.018; 61 vs. 49 years for H7H9, p < 0.001], concurrent diseases [18.8% (15/80) vs. 8.33% (9/108) for H5N1, p = 0.046; 58.6% (156/266) vs. 34.8% (135/388) for H7H9, p < 0.001], delayed confirmation [13 vs. 6 days for H5N1, p < 0.001; 10 vs. 8 days for H7N9, p = 0.011] in the fatalities and survivors, were risk factors for deaths. With regard to the H5N1 clusters, exposure to poultry [67.4% (29/43) vs. 45.2% (19/42), p = 0.039] was the higher risk for the primary than the secondary deaths. In conclusion, old age, comorbidities, delayed confirmation, along with poultry exposure are the major risks contributing to fatal outcomes in human HPAI and LPAI infections.",2017 Mar 4,"['Wu, Zu-Qun', 'Zhang, Yi', 'Zhao, Na', 'Yu, Zhao', 'Pan, Hao', 'Chan, Ta-Chien', 'Zhang, Zhi-Ruo', 'Liu, She-Lan']",Int J Environ Res Public Health,,,False
028382edbe67a35f1e099fa0607fa9a4922a45d1,PMC,Contribution of the Purinergic Receptor P2X7 to Development of Lung Immunopathology during Influenza Virus Infection,http://dx.doi.org/10.1128/mBio.00229-17,PMC5371412,28351919,CC BY,"An exacerbated immune response is one of the main causes of influenza-induced lung damage during infection. The molecular mechanisms regulating the fate of the initial immune response to infection, either as a protective response or as detrimental immunopathology, are not well understood. The purinergic receptor P2X7 is an ionotropic nucleotide-gated ion channel receptor expressed on immune cells that has been implicated in induction and maintenance of excessive inflammation. Here, we analyze the role of this receptor in a mouse model of influenza virus infection using a receptor knockout (KO) mouse strain. Our results demonstrate that the absence of the P2X7 receptor results in a better outcome to influenza virus infection characterized by reduced weight loss and increased survival upon experimental influenza challenge compared to wild-type mice. This effect was not virus strain specific. Overall lung pathology and apoptosis were reduced in virus-infected KO mice. Production of proinflammatory cytokines and chemokines such as interleukin-10 (IL-10), gamma interferon (IFN-γ), and CC chemokine ligand 2 (CCL2) was also reduced in the lungs of the infected KO mice. Infiltration of neutrophils and depletion of CD11b(+) macrophages, characteristic of severe influenza virus infection in mice, were lower in the KO animals. Together, these results demonstrate that activation of the P2X7 receptor is involved in the exacerbated immune response observed during influenza virus infection.",2017 Mar 28,"['Leyva-Grado, Victor H.', 'Ermler, Megan E.', 'Schotsaert, Michael', 'Gonzalez, Ma G.', 'Gillespie, Virginia', 'Lim, Jean K.', 'García-Sastre, Adolfo']",mBio,,,True
d0ea14c58420640a597ffbc7eaea38112c010609,PMC,Contribution of the Purinergic Receptor P2X7 to Development of Lung Immunopathology during Influenza Virus Infection,http://dx.doi.org/10.1128/mBio.00229-17,PMC5371412,28351919,CC BY,"An exacerbated immune response is one of the main causes of influenza-induced lung damage during infection. The molecular mechanisms regulating the fate of the initial immune response to infection, either as a protective response or as detrimental immunopathology, are not well understood. The purinergic receptor P2X7 is an ionotropic nucleotide-gated ion channel receptor expressed on immune cells that has been implicated in induction and maintenance of excessive inflammation. Here, we analyze the role of this receptor in a mouse model of influenza virus infection using a receptor knockout (KO) mouse strain. Our results demonstrate that the absence of the P2X7 receptor results in a better outcome to influenza virus infection characterized by reduced weight loss and increased survival upon experimental influenza challenge compared to wild-type mice. This effect was not virus strain specific. Overall lung pathology and apoptosis were reduced in virus-infected KO mice. Production of proinflammatory cytokines and chemokines such as interleukin-10 (IL-10), gamma interferon (IFN-γ), and CC chemokine ligand 2 (CCL2) was also reduced in the lungs of the infected KO mice. Infiltration of neutrophils and depletion of CD11b(+) macrophages, characteristic of severe influenza virus infection in mice, were lower in the KO animals. Together, these results demonstrate that activation of the P2X7 receptor is involved in the exacerbated immune response observed during influenza virus infection.",2017 Mar 28,"['Leyva-Grado, Victor H.', 'Ermler, Megan E.', 'Schotsaert, Michael', 'Gonzalez, Ma G.', 'Gillespie, Virginia', 'Lim, Jean K.', 'García-Sastre, Adolfo']",mBio,,,False
6ecd29c16591981be15bfdb0eccc6f804e70c3e0,PMC,Contribution of the Purinergic Receptor P2X7 to Development of Lung Immunopathology during Influenza Virus Infection,http://dx.doi.org/10.1128/mBio.00229-17,PMC5371412,28351919,CC BY,"An exacerbated immune response is one of the main causes of influenza-induced lung damage during infection. The molecular mechanisms regulating the fate of the initial immune response to infection, either as a protective response or as detrimental immunopathology, are not well understood. The purinergic receptor P2X7 is an ionotropic nucleotide-gated ion channel receptor expressed on immune cells that has been implicated in induction and maintenance of excessive inflammation. Here, we analyze the role of this receptor in a mouse model of influenza virus infection using a receptor knockout (KO) mouse strain. Our results demonstrate that the absence of the P2X7 receptor results in a better outcome to influenza virus infection characterized by reduced weight loss and increased survival upon experimental influenza challenge compared to wild-type mice. This effect was not virus strain specific. Overall lung pathology and apoptosis were reduced in virus-infected KO mice. Production of proinflammatory cytokines and chemokines such as interleukin-10 (IL-10), gamma interferon (IFN-γ), and CC chemokine ligand 2 (CCL2) was also reduced in the lungs of the infected KO mice. Infiltration of neutrophils and depletion of CD11b(+) macrophages, characteristic of severe influenza virus infection in mice, were lower in the KO animals. Together, these results demonstrate that activation of the P2X7 receptor is involved in the exacerbated immune response observed during influenza virus infection.",2017 Mar 28,"['Leyva-Grado, Victor H.', 'Ermler, Megan E.', 'Schotsaert, Michael', 'Gonzalez, Ma G.', 'Gillespie, Virginia', 'Lim, Jean K.', 'García-Sastre, Adolfo']",mBio,,,False
b1c3b2b1c4cf2f4e3cb4ac316dc9ad8d33946c77,PMC,Basic Scholarship in Biosafety Is Critically Needed To Reduce Risk of Laboratory Accidents,http://dx.doi.org/10.1128/mSphere.00010-17,PMC5371692,28405626,CC BY,"Our firm conducted a risk/benefit assessment of “gain-of-function” research, as part of the deliberative process following a U.S. moratorium on the research (U.S. Department of Health and Human Services, U.S. Government Gain-of-Function Deliberative Process and Research Funding Pause on Selected Gain-of-Function Research Involving Influenza, MERS, and SARS Viruses, 2014). Due to significant missing but theoretically acquirable data, our biosafety assessment faced limitations, and we were forced to provide a relative, instead of absolute, measure of risk (Gryphon Scientific, LLC, Risk and Benefit Analysis of Gain of Function Research, 2016). Here, we argue that many of these types of missing data represent large and stunning gaps in our knowledge of biosafety and argue that these missing data, once acquired via primary research efforts, would improve biosafety risk assessments and could be incorporated into biosafety practices to reduce risk of accidents. Governments invest billions in biological research; at least a small fraction of this support is warranted to prevent biological accidents.",2017 Mar 29,"['Ritterson, Ryan', 'Casagrande, Rocco']",mSphere,,,True
66adc3747695647a2654d4c3bad5d90a3acafbd1,PMC,Porcine Epidemic Diarrhea Virus Induces Autophagy to Benefit Its Replication,http://dx.doi.org/10.3390/v9030053,PMC5371808,28335505,CC BY,"The new porcine epidemic diarrhea (PED) has caused devastating economic losses to the swine industry worldwide. Despite extensive research on the relationship between autophagy and virus infection, the concrete role of autophagy in porcine epidemic diarrhea virus (PEDV) infection has not been reported. In this study, autophagy was demonstrated to be triggered by the effective replication of PEDV through transmission electron microscopy, confocal microscopy, and Western blot analysis. Moreover, autophagy was confirmed to benefit PEDV replication by using autophagy regulators and RNA interference. Furthermore, autophagy might be associated with the expression of inflammatory cytokines and have a positive feedback loop with the NF-κB signaling pathway during PEDV infection. This work is the first attempt to explore the complex interplay between autophagy and PEDV infection. Our findings might accelerate our understanding of the pathogenesis of PEDV infection and provide new insights into the development of effective therapeutic strategies.",2017 Mar 19,"['Guo, Xiaozhen', 'Zhang, Mengjia', 'Zhang, Xiaoqian', 'Tan, Xin', 'Guo, Hengke', 'Zeng, Wei', 'Yan, Guokai', 'Memon, Atta Muhammad', 'Li, Zhonghua', 'Zhu, Yinxing', 'Zhang, Bingzhou', 'Ku, Xugang', 'Wu, Meizhou', 'Fan, Shengxian', 'He, Qigai']",Viruses,,,True
0263ef539a1344a642b1f4ff11aee6bc6ca84a34,PMC,1st Workshop of the Canadian Society for Virology,http://dx.doi.org/10.3390/v9030054,PMC5371809,28335511,CC BY,"The 1st Workshop of the Canadian Society for Virology (CSV2016) was a Special Workshop of the 35th Annual Meeting for the American Society for Virology, held on 18 June 2016 on the beautiful Virginia Tech campus in Blacksburg, Virginia. The workshop provided a forum for discussion of recent advances in the field, in an informal setting conducive to interaction with colleagues. CSV2016 featured two internationally-renowned Canadian keynote speakers who discussed translational virology research; American Society for Virology President Grant McFadden (then from University of Florida, now relocated to Arizona State University) who presented his studies of oncolytic poxviruses, while Matthew Miller (McMaster University) reviewed the prospects for a universal influenza vaccine. The workshop also featured a variety of trainee oral and poster presentations, and a panel discussion on the topic of the future of the CSV and virus research in Canada.",2017 Mar 20,"['McCormick, Craig', 'Grandvaux, Nathalie']",Viruses,,,True
45b5b1c24269b3ee4c2f74aba8872482c0a6a934,PMC,Myeloid C-Type Lectin Receptors in Viral Recognition and Antiviral Immunity,http://dx.doi.org/10.3390/v9030059,PMC5371814,28327518,CC BY,"Recognition of viral glycans by pattern recognition receptors (PRRs) in innate immunity contributes to antiviral immune responses. C-type lectin receptors (CLRs) are PRRs capable of sensing glycans present in viral pathogens to activate antiviral immune responses such as phagocytosis, antigen processing and presentation, and subsequent T cell activation. The ability of CLRs to elicit and shape adaptive immunity plays a critical role in the inhibition of viral spread within the host. However, certain viruses exploit CLRs for viral entry into host cells to avoid immune recognition. To block CLR interactions with viral glycoproteins, antiviral strategies may involve the use of multivalent glycan carrier systems. In this review, we describe the role of CLRs in antiviral immunity and we highlight their dual function in viral clearance and exploitation by viral pathogens.",2017 Mar 22,"['Monteiro, João T.', 'Lepenies, Bernd']",Viruses,,,True
8e631c0c0bdbb5cf13818b5b71d39c145b045955,PMC,Epigenetic Landscape during Coronavirus Infection,http://dx.doi.org/10.3390/pathogens6010008,PMC5371896,28212305,CC BY,"Coronaviruses (CoV) comprise a large group of emerging human and animal pathogens, including the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) strains. The molecular mechanisms regulating emerging coronavirus pathogenesis are complex and include virus–host interactions associated with entry, replication, egress and innate immune control. Epigenetics research investigates the genetic and non-genetic factors that regulate phenotypic variation, usually caused by external and environmental factors that alter host expression patterns and performance without any change in the underlying genotype. Epigenetic modifications, such as histone modifications, DNA methylation, chromatin remodeling, and non-coding RNAs, function as important regulators that remodel host chromatin, altering host expression patterns and networks in a highly flexible manner. For most of the past two and a half decades, research has focused on the molecular mechanisms by which RNA viruses antagonize the signaling and sensing components that regulate induction of the host innate immune and antiviral defense programs upon infection. More recently, a growing body of evidence supports the hypothesis that viruses, even lytic RNA viruses that replicate in the cytoplasm, have developed intricate, highly evolved, and well-coordinated processes that are designed to regulate the host epigenome, and control host innate immune antiviral defense processes, thereby promoting robust virus replication and pathogenesis. In this article, we discuss the strategies that are used to evaluate the mechanisms by which viruses regulate the host epigenome, especially focusing on highly pathogenic respiratory RNA virus infections as a model. By combining measures of epigenome reorganization with RNA and proteomic datasets, we articulate a spatial-temporal data integration approach to identify regulatory genomic clusters and regions that play a crucial role in the host’s innate immune response, thereby defining a new viral antagonism mechanism following emerging coronavirus infection.",2017 Feb 15,"['Schäfer, Alexandra', 'Baric, Ralph S.']",Pathogens,,,True
435c259a0b1c77cb1fab63dabf76fa1637d8e645,PMC,Lactoferrin: Balancing Ups and Downs of Inflammation Due to Microbial Infections,http://dx.doi.org/10.3390/ijms18030501,PMC5372517,28257033,CC BY,"Lactoferrin (Lf) is a glycoprotein of the primary innate immune-defense system of mammals present in milk and other mucosal secretions. This protein of the transferrin family has broad antimicrobial properties by depriving pathogens from iron, or disrupting their plasma membranes through its highly cationic charge. Noteworthy, Lf also exhibits immunomodulatory activities performing up- and down-regulation of innate and adaptive immune cells, contributing to the homeostasis in mucosal surfaces exposed to myriad of microbial agents, such as the gastrointestinal and respiratory tracts. Although the inflammatory process is essential for the control of invasive infectious agents, the development of an exacerbated or chronic inflammation results in tissue damage with life-threatening consequences. In this review, we highlight recent findings in in vitro and in vivo models of the gut, lung, oral cavity, mammary gland, and liver infections that provide experimental evidence supporting the therapeutic role of human and bovine Lf in promoting some parameters of inflammation and protecting against the deleterious effects of bacterial, viral, fungal and protozoan-associated inflammation. Thus, this new knowledge of Lf immunomodulation paves the way to more effective design of treatments that include native or synthetic Lf derivatives, which may be useful to reduce immune-mediated tissue damage in infectious diseases.",2017 Mar 1,"['Drago-Serrano, Maria Elisa', 'Campos-Rodríguez, Rafael', 'Carrero, Julio César', 'de la Garza, Mireya']",Int J Mol Sci,,,True
8da5d4c7d3f991b1538e839ed944dcd2167112d0,PMC,Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse,http://dx.doi.org/10.3390/ijms18030563,PMC5372579,28273875,CC BY,"Renin angiotensin system (RAS) is known to play a key role in several diseases such as diabetes, and renal and cardiovascular pathologies. Its blockade has been demonstrated to delay chronic kidney disease progression and cardiovascular damage in diabetic patients. In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model. After 21 or 40 days of diabetes onset, mouse serums and tissues were analyzed for ACE and ACE2 enzyme activities and protein expression. ACE and ACE2 enzyme activities were detected in different tissues. Their expressions vary depending on the studied tissue. Thus, whereas ACE activity was highly expressed in lungs, ACE2 activity was highly expressed in pancreas among the studied tissues. Interestingly, we also observed that diabetes up-regulates ACE mainly in serum, lung, heart, and liver, and ACE2 mainly in serum, liver, and pancreas. In conclusion, we found a marked serum and pulmonary alteration in ACE activity of diabetic mice, suggesting a common regulation. The increase of ACE2 activity within the circulation in diabetic mice may be ascribed to a compensatory mechanism of RAS.",2017 Mar 5,"['Roca-Ho, Heleia', 'Riera, Marta', 'Palau, Vanesa', 'Pascual, Julio', 'Soler, Maria Jose']",Int J Mol Sci,,,True
04d774680876efd10e478ed5f2ef7a7a2e860acf,PMC,Genomic Loads and Genotypes of Respiratory Syncytial Virus: Viral Factors during Lower Respiratory Tract Infection in Chilean Hospitalized Infants,http://dx.doi.org/10.3390/ijms18030654,PMC5372666,28335547,CC BY,"The clinical impact of viral factors (types and viral loads) during respiratory syncytial virus (RSV) infection is still controversial, especially regarding newly described genotypes. In this study, infants with RSV bronchiolitis were recruited to describe the association of these viral factors with severity of infection. RSV antigenic types, genotypes, and viral loads were determined from hospitalized patients at Hospital Roberto del Río, Santiago, Chile. Cases were characterized by demographic and clinical information, including days of lower respiratory symptoms and severity. A total of 86 patients were included: 49 moderate and 37 severe cases. During 2013, RSV-A was dominant (86%). RSV-B predominated in 2014 (92%). Phylogenetic analyses revealed circulation of GA2, Buenos Aires (BA), and Ontario (ON) genotypes. No association was observed between severity of infection and RSV group (p = 0.69) or genotype (p = 0.87). After a clinical categorization of duration of illness, higher RSV genomic loads were detected in infants evaluated earlier in their disease (p < 0.001) and also in infants evaluated later, but coursing a more severe infection (p = 0.04). Although types and genotypes did not associate with severity in our children, higher RSV genomic loads and delayed viral clearance in severe patients define a group that might benefit from new antiviral therapies.",2017 Mar 21,"['Espinosa, Yazmín', 'San Martín, Camila', 'Torres, Alejandro A.', 'Farfán, Mauricio J.', 'Torres, Juan P.', 'Avadhanula, Vasanthi', 'Piedra, Pedro A.', 'Tapia, Lorena I.']",Int J Mol Sci,,,True
dd0fdbeb9f3ba21911ba2c667ff85f2e43c696a6,PMC,Genomic Loads and Genotypes of Respiratory Syncytial Virus: Viral Factors during Lower Respiratory Tract Infection in Chilean Hospitalized Infants,http://dx.doi.org/10.3390/ijms18030654,PMC5372666,28335547,CC BY,"The clinical impact of viral factors (types and viral loads) during respiratory syncytial virus (RSV) infection is still controversial, especially regarding newly described genotypes. In this study, infants with RSV bronchiolitis were recruited to describe the association of these viral factors with severity of infection. RSV antigenic types, genotypes, and viral loads were determined from hospitalized patients at Hospital Roberto del Río, Santiago, Chile. Cases were characterized by demographic and clinical information, including days of lower respiratory symptoms and severity. A total of 86 patients were included: 49 moderate and 37 severe cases. During 2013, RSV-A was dominant (86%). RSV-B predominated in 2014 (92%). Phylogenetic analyses revealed circulation of GA2, Buenos Aires (BA), and Ontario (ON) genotypes. No association was observed between severity of infection and RSV group (p = 0.69) or genotype (p = 0.87). After a clinical categorization of duration of illness, higher RSV genomic loads were detected in infants evaluated earlier in their disease (p < 0.001) and also in infants evaluated later, but coursing a more severe infection (p = 0.04). Although types and genotypes did not associate with severity in our children, higher RSV genomic loads and delayed viral clearance in severe patients define a group that might benefit from new antiviral therapies.",2017 Mar 21,"['Espinosa, Yazmín', 'San Martín, Camila', 'Torres, Alejandro A.', 'Farfán, Mauricio J.', 'Torres, Juan P.', 'Avadhanula, Vasanthi', 'Piedra, Pedro A.', 'Tapia, Lorena I.']",Int J Mol Sci,,,False
61b90922be286db0340b0543233488c3764c611d,PMC,Chemical and Conformational Diversity of Modified Nucleosides Affects tRNA Structure and Function,http://dx.doi.org/10.3390/biom7010029,PMC5372741,28300792,CC BY,"RNAs are central to all gene expression through the control of protein synthesis. Four major nucleosides, adenosine, guanosine, cytidine and uridine, compose RNAs and provide sequence variation, but are limited in contributions to structural variation as well as distinct chemical properties. The ability of RNAs to play multiple roles in cellular metabolism is made possible by extensive variation in length, conformational dynamics, and the over 100 post-transcriptional modifications. There are several reviews of the biochemical pathways leading to RNA modification, but the physicochemical nature of modified nucleosides and how they facilitate RNA function is of keen interest, particularly with regard to the contributions of modified nucleosides. Transfer RNAs (tRNAs) are the most extensively modified RNAs. The diversity of modifications provide versatility to the chemical and structural environments. The added chemistry, conformation and dynamics of modified nucleosides occurring at the termini of stems in tRNA’s cloverleaf secondary structure affect the global three-dimensional conformation, produce unique recognition determinants for macromolecules to recognize tRNAs, and affect the accurate and efficient decoding ability of tRNAs. This review will discuss the impact of specific chemical moieties on the structure, stability, electrochemical properties, and function of tRNAs.",2017 Mar 16,"['Väre, Ville Y. P.', 'Eruysal, Emily R.', 'Narendran, Amithi', 'Sarachan, Kathryn L.', 'Agris, Paul F.']",Biomolecules,,,True
5957e56769edb4d25f47287befe49a683b8e8f76,PMC,Chemical and Conformational Diversity of Modified Nucleosides Affects tRNA Structure and Function,http://dx.doi.org/10.3390/biom7010029,PMC5372741,28300792,CC BY,"RNAs are central to all gene expression through the control of protein synthesis. Four major nucleosides, adenosine, guanosine, cytidine and uridine, compose RNAs and provide sequence variation, but are limited in contributions to structural variation as well as distinct chemical properties. The ability of RNAs to play multiple roles in cellular metabolism is made possible by extensive variation in length, conformational dynamics, and the over 100 post-transcriptional modifications. There are several reviews of the biochemical pathways leading to RNA modification, but the physicochemical nature of modified nucleosides and how they facilitate RNA function is of keen interest, particularly with regard to the contributions of modified nucleosides. Transfer RNAs (tRNAs) are the most extensively modified RNAs. The diversity of modifications provide versatility to the chemical and structural environments. The added chemistry, conformation and dynamics of modified nucleosides occurring at the termini of stems in tRNA’s cloverleaf secondary structure affect the global three-dimensional conformation, produce unique recognition determinants for macromolecules to recognize tRNAs, and affect the accurate and efficient decoding ability of tRNAs. This review will discuss the impact of specific chemical moieties on the structure, stability, electrochemical properties, and function of tRNAs.",2017 Mar 16,"['Väre, Ville Y. P.', 'Eruysal, Emily R.', 'Narendran, Amithi', 'Sarachan, Kathryn L.', 'Agris, Paul F.']",Biomolecules,,,False
9c438a13c9083e842b860ae7b477e671e60fb4cb,PMC,Novel Pharmacological Activity of Artesunate and Artemisinin: Their Potential as Anti-Tubercular Agents,http://dx.doi.org/10.3390/jcm6030030,PMC5372999,28287416,CC BY,"Tuberculosis is a major infectious disease that globally causes the highest human mortality. From this aspect, this study was carried out to evaluate novel pharmacological activities/effects of artesunate and artemisinin causing anti-tubercular activity/effects against Mycobacterium tuberculosis (Mtb). The anti-Mtb activities/effects of artesunate and artemisinin were evaluated using different anti-Mtb indicator assays, such as the resazurin microtiter assay, the Mycobacteria Growth Indicator Tube (MGIT) 960 system assay, and the Ogawa slant medium assay, as well as in vivo tests. Artesunate showed selective anti-Mtb effects by strongly inhibiting the growth of Mtb compared to artemisinin, and consistently induced anti-Mtb activity/effects by effectively inhibiting Mtb in the MGIT 960 system and in Ogawa slant medium for 21 days with a single dose; its minimum inhibitory concentration was 300 µg/mL in in vitro testing. Furthermore, artesunate demonstrated an anti-tubercular effect/action with a daily dose of 3.5 mg/kg in an in vivo test for four weeks, which did not indicate or induce toxicity and side effects. These results demonstrate that artesunate effectively inhibits the growth and/or proliferation of Mtb through novel pharmacological activities/actions, as well as induces anti-Mtb activity. This study shows its potential as a potent candidate agent for developing new anti-tuberculosis drugs of an effective/safe next generation, and suggests novel insights into its effective use by repurposing existing drugs through new pharmacological activity/effects as one of the substantive alternatives for inhibiting tuberculosis.",2017 Mar 10,"Choi, Won Hyung",J Clin Med,,,True
9ac7ff68cae35ddd75b3e7ca8d267ac78d46daa6,PMC,"Epidemiological evaluation of cat health at a first-response animal shelter in Fukushima, following the Great East Japan Earthquakes of 2011",http://dx.doi.org/10.1371/journal.pone.0174406,PMC5373578,28358820,CC BY,"The Great East Japan Earthquakes of March 11, 2011 caused immense harm to the community and subsequent nuclear accident in Fukushima Prefecture extended the damage. Local residents were forced to evacuated without pets and the left behind animals were rescued from the restricted zone one month later. Unplanned animal rescue and unregulated sheltering caused secondary damage to animals such as disease epidemics at impounded animal shelter. The purpose of this study was to retrospectively evaluate the incidence of upper respiratory infection (URI) and diarrhea in cats at the first response animal shelter in Fukushima, and investigate factors affecting the duration of disease and determinants of treatments performed. Eighty percent and 59% of impounded cats developed URI, 71% and 54% of cats developed diarrhea, and 91% and 83% of cats had at least one disease in 2011 and 2012, respectively. Uses of multiple drug administration (more than five drugs) was associated with prolonged URI and diarrhea. Multiple antibiotics, antihistamines, interferon, and steroids were associated with relapse of and prolonged URI. Developing a standardized treatment protocol for commonly observed diseases at Japanese animal shelters to prevent and control diseases, to promote animal welfare, and protect public health in the face of future disasters is overdue.",2017 Mar 30,"['Tanaka, Aki', 'Kass, Philip H.', 'Martinez -Lopez, Beatriz', 'Hayama, Shinichi']",PLoS One,,,True
322c0b7c44d12a2f239646697ad78f5098542ea2,PMC,SheddomeDB: the ectodomain shedding database for membrane-bound shed markers,http://dx.doi.org/10.1186/s12859-017-1465-7,PMC5374707,28361715,CC BY,"BACKGROUND: A number of membrane-anchored proteins are known to be released from cell surface via ectodomain shedding. The cleavage and release of membrane proteins has been shown to modulate various cellular processes and disease pathologies. Numerous studies revealed that cell membrane molecules of diverse functional groups are subjected to proteolytic cleavage, and the released soluble form of proteins may modulate various signaling processes. Therefore, in addition to the secreted protein markers that undergo secretion through the secretory pathway, the shed membrane proteins may comprise an additional resource of noninvasive and accessible biomarkers. In this context, identifying the membrane-bound proteins that will be shed has become important in the discovery of clinically noninvasive biomarkers. Nevertheless, a data repository for biological and clinical researchers to review the shedding information, which is experimentally validated, for membrane-bound protein shed markers is still lacking. RESULTS: In this study, the database SheddomeDB was developed to integrate publicly available data of the shed membrane proteins. A comprehensive literature survey was performed to collect the membrane proteins that were verified to be cleaved or released in the supernatant by immunological-based validation experiments. From 436 studies on shedding, 401 validated shed membrane proteins were included, among which 199 shed membrane proteins have not been annotated or validated yet by existing cleavage databases. SheddomeDB attempted to provide a comprehensive shedding report, including the regulation of shedding machinery and the related function or diseases involved in the shedding events. In addition, our published tool ShedP was embedded into SheddomeDB to support researchers for predicting the shedding event on unknown or unrecorded membrane proteins. CONCLUSIONS: To the best of our knowledge, SheddomeDB is the first database for the identification of experimentally validated shed membrane proteins and currently may provide the most number of membrane proteins for reviewing the shedding information. The database included membrane-bound shed markers associated with numerous cellular processes and diseases, and some of these markers are potential novel markers because they are not annotated or validated yet in other databases. SheddomeDB may provide a useful resource for discovering membrane-bound shed markers. The interactive web of SheddomeDB is publicly available at http://bal.ym.edu.tw/SheddomeDB/. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-017-1465-7) contains supplementary material, which is available to authorized users.",2017 Mar 14,"['Tien, Wei-Sheng', 'Chen, Jun-Hong', 'Wu, Kun-Pin']",BMC Bioinformatics,,,False
b9f063ab66715b75706b11ab3b0a2af52294cd5b,PMC,SheddomeDB: the ectodomain shedding database for membrane-bound shed markers,http://dx.doi.org/10.1186/s12859-017-1465-7,PMC5374707,28361715,CC BY,"BACKGROUND: A number of membrane-anchored proteins are known to be released from cell surface via ectodomain shedding. The cleavage and release of membrane proteins has been shown to modulate various cellular processes and disease pathologies. Numerous studies revealed that cell membrane molecules of diverse functional groups are subjected to proteolytic cleavage, and the released soluble form of proteins may modulate various signaling processes. Therefore, in addition to the secreted protein markers that undergo secretion through the secretory pathway, the shed membrane proteins may comprise an additional resource of noninvasive and accessible biomarkers. In this context, identifying the membrane-bound proteins that will be shed has become important in the discovery of clinically noninvasive biomarkers. Nevertheless, a data repository for biological and clinical researchers to review the shedding information, which is experimentally validated, for membrane-bound protein shed markers is still lacking. RESULTS: In this study, the database SheddomeDB was developed to integrate publicly available data of the shed membrane proteins. A comprehensive literature survey was performed to collect the membrane proteins that were verified to be cleaved or released in the supernatant by immunological-based validation experiments. From 436 studies on shedding, 401 validated shed membrane proteins were included, among which 199 shed membrane proteins have not been annotated or validated yet by existing cleavage databases. SheddomeDB attempted to provide a comprehensive shedding report, including the regulation of shedding machinery and the related function or diseases involved in the shedding events. In addition, our published tool ShedP was embedded into SheddomeDB to support researchers for predicting the shedding event on unknown or unrecorded membrane proteins. CONCLUSIONS: To the best of our knowledge, SheddomeDB is the first database for the identification of experimentally validated shed membrane proteins and currently may provide the most number of membrane proteins for reviewing the shedding information. The database included membrane-bound shed markers associated with numerous cellular processes and diseases, and some of these markers are potential novel markers because they are not annotated or validated yet in other databases. SheddomeDB may provide a useful resource for discovering membrane-bound shed markers. The interactive web of SheddomeDB is publicly available at http://bal.ym.edu.tw/SheddomeDB/. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-017-1465-7) contains supplementary material, which is available to authorized users.",2017 Mar 14,"['Tien, Wei-Sheng', 'Chen, Jun-Hong', 'Wu, Kun-Pin']",BMC Bioinformatics,,,True
84e8a4145f06c604f8542ee458480c8fa50bd1cf,PMC,Dielectrophoresis for Biomedical Sciences Applications: A Review,http://dx.doi.org/10.3390/s17030449,PMC5375735,28245552,CC BY,"Dielectrophoresis (DEP) is a label-free, accurate, fast, low-cost diagnostic technique that uses the principles of polarization and the motion of bioparticles in applied electric fields. This technique has been proven to be beneficial in various fields, including environmental research, polymer research, biosensors, microfluidics, medicine and diagnostics. Biomedical science research is one of the major research areas that could potentially benefit from DEP technology for diverse applications. Nevertheless, many medical science research investigations have yet to benefit from the possibilities offered by DEP. This paper critically reviews the fundamentals, recent progress, current challenges, future directions and potential applications of research investigations in the medical sciences utilizing DEP technique. This review will also act as a guide and reference for medical researchers and scientists to explore and utilize the DEP technique in their research fields.",2017 Feb 24,"['Abd Rahman, Nurhaslina', 'Ibrahim, Fatimah', 'Yafouz, Bashar']",Sensors (Basel),,,True
6e67417fbe15bbfa1dc530ceb8a41c796074aa9b,PMC,Ambra1 spatially regulates Src activity and Src/FAK-mediated cancer cell invasion via trafficking networks,http://dx.doi.org/10.7554/eLife.23172,PMC5376188,28362576,CC BY,"Here, using mouse squamous cell carcinoma cells, we report a completely new function for the autophagy protein Ambra1 as the first described ‘spatial rheostat’ controlling the Src/FAK pathway. Ambra1 regulates the targeting of active phospho-Src away from focal adhesions into autophagic structures that cancer cells use to survive adhesion stress. Ambra1 binds to both FAK and Src in cancer cells. When FAK is present, Ambra1 is recruited to focal adhesions, promoting FAK-regulated cancer cell direction-sensing and invasion. However, when Ambra1 cannot bind to FAK, abnormally high levels of phospho-Src and phospho-FAK accumulate at focal adhesions, positively regulating adhesion and invasive migration. Spatial control of active Src requires the trafficking proteins Dynactin one and IFITM3, which we identified as Ambra1 binding partners by interaction proteomics. We conclude that Ambra1 is a core component of an intracellular trafficking network linked to tight spatial control of active Src and FAK levels, and so crucially regulates their cancer-associated biological outputs. DOI: http://dx.doi.org/10.7554/eLife.23172.001",,"['Schoenherr, Christina', 'Byron, Adam', 'Sandilands, Emma', 'Paliashvili, Ketevan', 'Baillie, George S', 'Garcia-Munoz, Amaya', 'Valacca, Cristina', 'Cecconi, Francesco', 'Serrels, Bryan', 'Frame, Margaret C']",eLife.; 6:e23172,,,True
4c21ac102e96cf6a038edb3fd4fb7d7dd4471170,PMC,Surveillance for respiratory infectious diseases caused by 6 common viruses in a recruit training site in the Northern region of China,http://dx.doi.org/10.1186/s40779-017-0120-y,PMC5376280,28373908,CC BY,"BACKGROUND: Recruit training sites are places with a high incidence of respiratory infectious diseases. Effective surveillance for acute respiratory infectious diseases in a recruit training site is an important way to prevent disease outbreaks. METHODS: Eight hundred recruits (722 males and 78 females) enlisted in autumn 2015 received a background survey within 24 h of settlement at the recruit training site, including their general personal information, vaccination history, mental status and clinical symptoms. Then, nasopharyngeal swabs of these recruits were collected to detect common respiratory pathogens [influenza virus type A, influenza virus type B, adenovirus (Adv), human respiratory syncytial virus, human bocavirus and human metapneumovirus] by PCR. In addition, fasting venous blood was collected in the morning for adenovirus IgG antibody detection. During the three months of training, the recruits were monitored for symptoms of respiratory infection, and nasopharyngeal swabs were collected from those with an axillary temperature ≥38 °C and other respiratory symptoms within 4 h of symptom onset. Samples were further examined by PCR. RESULTS: Among the 795 effective nasopharyngeal swab samples collected during survey, two cases of group C type 1 adenovirus were identified by PCR. During the 3 months of training, fever and respiratory symptoms occurred in 39 recruits (incidence rate of 4.9%) and 5 cases of adenovirus were detected (positive rate of 12.8%). Genotyping showed 3 cases of type 4 adenovirus and 2 of type 3 adenovirus. No type 7, 14 or 55 adenovirus was detected. The Adv-IgG positive rate of recruits was 48.2%. Among the 5 Adv positive cases with fever and respiratory symptoms, 4 were Adv-IgG positive. CONCLUSION: The pathogen carrier rate in recruits was low, and only group C adenovirus, which causes mild infection in humans, was detected. No respiratory outbreak was observed at the recruit training site, and sporadic cases were mainly caused by type 3 and type 4 adenoviruses.",2017 Apr 1,"['Chen, Wei-Wei', 'Xu, Wen', 'Xie, Yang-Xin', 'Zhang, Yun-Hui', 'Wu, Dan', 'Wang, Fu-Sheng', 'Zhao, Min']",Mil Med Res,,,True
7f3106f6c5402784319dd722bbbaaa5f5b59df1f,PMC,Chemical property based sequence characterization of PpcA and its homolog proteins PpcB-E: A mathematical approach,http://dx.doi.org/10.1371/journal.pone.0175031,PMC5376323,28362850,CC BY,"Periplasmic c7 type cytochrome A (PpcA) protein is determined in Geobacter sulfurreducens along with its other four homologs (PpcB-E). From the crystal structure viewpoint the observation emerges that PpcA protein can bind with Deoxycholate (DXCA), while its other homologs do not. But it is yet to be established with certainty the reason behind this from primary protein sequence information. This study is primarily based on primary protein sequence analysis through the chemical basis of embedded amino acids. Firstly, we look for the chemical group specific score of amino acids. Along with this, we have developed a new methodology for the phylogenetic analysis based on chemical group dissimilarities of amino acids. This new methodology is applied to the cytochrome c7 family members and pinpoint how a particular sequence is differing with others. Secondly, we build a graph theoretic model on using amino acid sequences which is also applied to the cytochrome c7 family members and some unique characteristics and their domains are highlighted. Thirdly, we search for unique patterns as subsequences which are common among the group or specific individual member. In all the cases, we are able to show some distinct features of PpcA that emerges PpcA as an outstanding protein compared to its other homologs, resulting towards its binding with deoxycholate. Similarly, some notable features for the structurally dissimilar protein PpcD compared to the other homologs are also brought out. Further, the five members of cytochrome family being homolog proteins, they must have some common significant features which are also enumerated in this study.",2017 Mar 31,"['Das, Jayanta Kumar', 'Pal Choudhury, Pabitra']",PLoS One,,,True
abedfe23f4c5186a7c413558973c391b5259d3b7,PMC,Chemical property based sequence characterization of PpcA and its homolog proteins PpcB-E: A mathematical approach,http://dx.doi.org/10.1371/journal.pone.0175031,PMC5376323,28362850,CC BY,"Periplasmic c7 type cytochrome A (PpcA) protein is determined in Geobacter sulfurreducens along with its other four homologs (PpcB-E). From the crystal structure viewpoint the observation emerges that PpcA protein can bind with Deoxycholate (DXCA), while its other homologs do not. But it is yet to be established with certainty the reason behind this from primary protein sequence information. This study is primarily based on primary protein sequence analysis through the chemical basis of embedded amino acids. Firstly, we look for the chemical group specific score of amino acids. Along with this, we have developed a new methodology for the phylogenetic analysis based on chemical group dissimilarities of amino acids. This new methodology is applied to the cytochrome c7 family members and pinpoint how a particular sequence is differing with others. Secondly, we build a graph theoretic model on using amino acid sequences which is also applied to the cytochrome c7 family members and some unique characteristics and their domains are highlighted. Thirdly, we search for unique patterns as subsequences which are common among the group or specific individual member. In all the cases, we are able to show some distinct features of PpcA that emerges PpcA as an outstanding protein compared to its other homologs, resulting towards its binding with deoxycholate. Similarly, some notable features for the structurally dissimilar protein PpcD compared to the other homologs are also brought out. Further, the five members of cytochrome family being homolog proteins, they must have some common significant features which are also enumerated in this study.",2017 Mar 31,"['Das, Jayanta Kumar', 'Pal Choudhury, Pabitra']",PLoS One,,,False
aa17d26d0413ff025da757063e2fbe0a6bf2577e,PMC,Chemical property based sequence characterization of PpcA and its homolog proteins PpcB-E: A mathematical approach,http://dx.doi.org/10.1371/journal.pone.0175031,PMC5376323,28362850,CC BY,"Periplasmic c7 type cytochrome A (PpcA) protein is determined in Geobacter sulfurreducens along with its other four homologs (PpcB-E). From the crystal structure viewpoint the observation emerges that PpcA protein can bind with Deoxycholate (DXCA), while its other homologs do not. But it is yet to be established with certainty the reason behind this from primary protein sequence information. This study is primarily based on primary protein sequence analysis through the chemical basis of embedded amino acids. Firstly, we look for the chemical group specific score of amino acids. Along with this, we have developed a new methodology for the phylogenetic analysis based on chemical group dissimilarities of amino acids. This new methodology is applied to the cytochrome c7 family members and pinpoint how a particular sequence is differing with others. Secondly, we build a graph theoretic model on using amino acid sequences which is also applied to the cytochrome c7 family members and some unique characteristics and their domains are highlighted. Thirdly, we search for unique patterns as subsequences which are common among the group or specific individual member. In all the cases, we are able to show some distinct features of PpcA that emerges PpcA as an outstanding protein compared to its other homologs, resulting towards its binding with deoxycholate. Similarly, some notable features for the structurally dissimilar protein PpcD compared to the other homologs are also brought out. Further, the five members of cytochrome family being homolog proteins, they must have some common significant features which are also enumerated in this study.",2017 Mar 31,"['Das, Jayanta Kumar', 'Pal Choudhury, Pabitra']",PLoS One,,,False
4329714c2818a1caa58260ce4f82652106b535a9,PMC,"Actual measurement, hygrothermal response experiment and growth prediction analysis of microbial contamination of central air conditioning system in Dalian, China",http://dx.doi.org/10.1038/srep44190,PMC5377260,28367963,CC BY,"The microbial contamination of central air conditioning system is one of the important factors that affect the indoor air quality. Actual measurement and analysis were carried out on microbial contamination in central air conditioning system at a venue in Dalian, China. Illumina miseq method was used and three fungal samples of two units were analysed by high throughput sequencing. Results showed that the predominant fungus in air conditioning unit A and B were Candida spp. and Cladosporium spp., and two fungus were further used in the hygrothermal response experiment. Based on the data of Cladosporium in hygrothermal response experiment, this paper used the logistic equation and the Gompertz equation to fit the growth predictive model of Cladosporium genera in different temperature and relative humidity conditions, and the square root model was fitted based on the two environmental factors. In addition, the models were carried on the analysis to verify the accuracy and feasibility of the established model equation.",2017 Apr 3,"['Lv, Yang', 'Hu, Guangyao', 'Wang, Chunyang', 'Yuan, Wenjie', 'Wei, Shanshan', 'Gao, Jiaoqi', 'Wang, Boyuan', 'Song, Fangchao']",Sci Rep,,,True
615071c8c959f24857b1bad521cc432b59719bfb,PMC,Spread from the Sink to the Patient: In Situ Study Using Green Fluorescent Protein (GFP)-Expressing Escherichia coli To Model Bacterial Dispersion from Hand-Washing Sink-Trap Reservoirs,http://dx.doi.org/10.1128/AEM.03327-16,PMC5377511,28235877,CC BY,"There have been an increasing number of reports implicating Gammaproteobacteria as often carrying genes of drug resistance from colonized sink traps to vulnerable hospitalized patients. However, the mechanism of transmission from the wastewater of the sink P-trap to patients remains poorly understood. Herein we report the use of a designated hand-washing sink lab gallery to model dispersion of green fluorescent protein (GFP)-expressing Escherichia coli from sink wastewater to the surrounding environment. We found no dispersion of GFP-expressing E. coli directly from the P-trap to the sink basin or surrounding countertop with coincident water flow from a faucet. However, when the GFP-expressing E. coli cells were allowed to mature in the P-trap under conditions similar to those in a hospital environment, a GFP-expressing E. coli-containing putative biofilm extended upward over 7 days to reach the strainer. This subsequently resulted in droplet dispersion to the surrounding areas (<30 in.) during faucet operation. We also demonstrated that P-trap colonization could occur by retrograde transmission along a common pipe. We postulate that the organisms mobilize up to the strainer from the P-trap, resulting in droplet dispersion rather than dispersion directly from the P-trap. This work helps to further define the mode of transmission of bacteria from a P-trap reservoir to a vulnerable hospitalized patient. IMPORTANCE Many recent reports demonstrate that sink drain pipes become colonized with highly consequential multidrug-resistant bacteria, which then results in hospital-acquired infections. However, the mechanism of dispersal of bacteria from the sink to patients has not been fully elucidated. Through establishment of a unique sink gallery, this work found that a staged mode of transmission involving biofilm growth from the lower pipe to the sink strainer and subsequent splatter to the bowl and surrounding area occurs rather than splatter directly from the water in the lower pipe. We have also demonstrated that bacterial transmission can occur via connections in wastewater plumbing to neighboring sinks. This work helps to more clearly define the mechanism and risk of transmission from a wastewater source to hospitalized patients in a world with increasingly antibiotic-resistant bacteria that can thrive in wastewater environments and cause infections in vulnerable patients.",2017 Mar 31,"['Kotay, Shireen', 'Chai, Weidong', 'Guilford, William', 'Barry, Katie', 'Mathers, Amy J.']",Appl Environ Microbiol,,,True
2e34c8495ee4de8e0607b48585b97fa0c0da9dc9,PMC,Cell Cycle-independent Role of Cyclin D3 in Host Restriction of Influenza Virus Infection,http://dx.doi.org/10.1074/jbc.M117.776112,PMC5377818,28130444,CC BY,"To identify new host factors that modulate the replication of influenza A virus, we performed a yeast two-hybrid screen using the cytoplasmic tail of matrix protein 2 from the highly pathogenic H5N1 strain. The screen revealed a high-score interaction with cyclin D3, a key regulator of cell cycle early G(1) phase. M2-cyclin D3 interaction was validated through GST pull-down and recapitulated in influenza A/WSN/33-infected cells. Knockdown of Ccnd3 by small interfering RNA significantly enhanced virus progeny titers in cell culture supernatants. Interestingly, the increase in virus production was due to cyclin D3 deficiency per se and not merely a consequence of cell cycle deregulation. A combined knockdown of Ccnd3 and Rb1, which rescued cell cycle progression into S phase, failed to normalize virus production. Infection by influenza A virus triggered redistribution of cyclin D3 from the nucleus to the cytoplasm, followed by its proteasomal degradation. When overexpressed in HEK 293T cells, cyclin D3 impaired binding of M2 with M1, which is essential for proper assembly of progeny virions, lending further support to its role as a putative restriction factor. Our study describes the identification and characterization of cyclin D3 as a novel interactor of influenza A virus M2 protein. We hypothesize that competitive inhibition of M1-M2 interaction by cyclin D3 impairs infectious virion formation and results in attenuated virus production. In addition, we provide mechanistic insights into the dynamic interplay of influenza virus with the host cell cycle machinery during infection.",2017 Mar 24,"['Fan, Ying', 'Mok, Chris Ka-Pun', 'Chan, Michael Chi Wai', 'Zhang, Yang', 'Nal, Béatrice', 'Kien, François', 'Bruzzone, Roberto', 'Sanyal, Sumana']",J Biol Chem,,,True
69b4d83503fda10464dc830c82e76af9b8fbf73f,PMC,Evaluation of Alere i RSV for Rapid Detection of Respiratory Syncytial Virus in Children Hospitalized with Acute Respiratory Tract Infection,http://dx.doi.org/10.1128/JCM.02433-16,PMC5377829,28077700,CC BY,"Alere i RSV is a novel rapid test which applies a nicking enzyme amplification reaction to detect respiratory syncytial virus in point-of-care settings. In this study, we evaluated the Alere i RSV assay by using frozen nasopharyngeal swab samples that were collected in viral transport medium from children hospitalized with acute respiratory tract infection during the 2015-2016 winter season. Alere i RSV assay results were compared to those for Altona RealStar RSV real-time reverse transcription-PCR (RT-PCR). We found that the overall sensitivity and specificity of the Alere i RSV test was 100% (95% confidence intervals [CI], 93% to 100%) and 97% (95% CI, 89% to 100%), respectively. Positive samples were identified within 5 to 7 min from sample collection. Overall, the Alere i RSV test performed well compared to the RT-PCR assay and has the potential to facilitate the detection of RSV in point-of-care settings.",2017 Apr 24,"['Peters, Rebecca Marie', 'Schnee, Sarah Valerie', 'Tabatabai, Julia', 'Schnitzler, Paul', 'Pfeil, Johannes']",J Clin Microbiol,,,True
0c589675855cd6a533025c50fb319ecd269c2d0d,PMC,Porcine Reproductive and Respiratory Syndrome Virus Infection Induces Stress Granule Formation Depending on Protein Kinase R-like Endoplasmic Reticulum Kinase (PERK) in MARC-145 Cells,http://dx.doi.org/10.3389/fcimb.2017.00111,PMC5378712,28421170,CC BY,"Stress granules (SGs) are sites of mRNA storage that are formed in response to various conditions of stress, including viral infections. Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has been devastating the swine industry worldwide since the late 1980s. In this study, we found that infection of PRRSV strain WUH3 (genotype 2 PRRSV) induced stable formation of robust SGs in MARC-145 cells, as demonstrated by the recruitment of marker proteins of SGs, including TIA1, G3BP1, and eIF3η. Treatment with specific inhibitors or siRNAs against the stress kinases that are involved in SG formation revealed that PRRSV induced SG formation through a PERK (protein kinase R–like endoplasmic reticulum kinase)-dependent mechanism. Impairment of SG assembly by concomitant knockdown of the SG marker proteins (TIA1, G3BP1, and TIAR) did not affect PRRSV growth, while significantly enhanced PRRSV-induced NF-κB subunit p65 phosphorylation and inflammatory cytokine production. Taken together, our results demonstrate that PRRSV induces SG formation via a PERK-dependent pathway and that SGs are involved in the signaling pathway of the PRRSV-induced inflammatory response in MARC-145 cells.",2017 Apr 4,"['Zhou, Yanrong', 'Fang, Liurong', 'Wang, Dang', 'Cai, Kaimei', 'Chen, Huanchun', 'Xiao, Shaobo']",Front Cell Infect Microbiol,,,True
7523a7acead9732b16e087fd2a3544533af20ce3,PMC,Discovery and genetic analysis of novel coronaviruses in least horseshoe bats in southwestern China,http://dx.doi.org/10.1038/emi.2016.140,PMC5378919,28352124,CC BY,"To investigate bat coronaviruses (CoVs), we collected 132 rectal swabs and urine samples from five bat species in three countries in southwestern China. Seven CoVs belonging to distinct groups of severe acute respiratory syndrome (SARS)-like CoVs and α-CoVs were detected in samples from least horseshoe bats. Samples from other bat species were negative for these viruses, indicating that the least horseshoe bat represents one of the natural reservoirs and mixers for strains of CoVs and has a pivotal role in the evolution and dissemination of these viruses. The genetic and evolutionary characteristics of these strains were described. Whole-genome sequencing of a new isolate (F46) from a rectal swab from a least horseshoe bat showed that it contained 29 699 nucleotides, excluding the poly (A) tail, with 13 open reading frames (ORFs). Phylogenetic and recombination analyses of F46 provided evidence of natural recombination between bat SARS-like CoVs (Rs3367 and LYRa11) or SARS-CoV (BJ01), suggesting that F46 could be a new recombinant virus from SARS-like CoVs or SARS-CoVs.",2017 Mar 29,"['Wang, Lihua', 'Fu, Shihong', 'Cao, Yuxi', 'Zhang, Hailin', 'Feng, Yun', 'Yang, Weihong', 'Nie, Kai', 'Ma, Xuejun', 'Liang, Guodong']",Emerg Microbes Infect,,,True
57bac09c0563474a03a233b1e7f60ed8c82a9642,PMC,"In silico CD4+, CD8+ T-cell and B-cell immunity associated immunogenic epitope prediction and HLA distribution analysis of Zika virus",http://dx.doi.org/10.17179/excli2016-719,PMC5379118,28435428,CC BY,"Zika virus (ZIKV) is a mosquito-borne flavivirus distributed all over Africa, South America and Asia. The infection with the virus may cause acute febrile sickness that clinically resembles dengue fever, yet there is no vaccine, no satisfactory treatment, and no means of evaluating the risk of the disease or prognosis in the infected people. In the present study, the efficacy of the host's immune response in reducing the risk of infectious diseases was taken into account to carry out immuno-informatics driven epitope screening strategy of vaccine candidates against ZIKV. In this study, HLA distribution analysis was done to ensure the coverage of the vast majority of the population. Systematic screening of effective dominant immunogens was done with the help of Immune Epitope & ABCPred databases. The outcomes suggested that the predicted epitopes may be protective immunogens with highly conserved sequences and bear potential to induce both protective neutralizing antibodies, T & B cell responses. A total of 25 CD4+ and 16 CD8+ peptides were screened for T-cell mediated immunity. The predicted epitope ""TGLDFSDLYYLTMNNKHWLV"" was selected as a highly immunogenic epitope for humoral immunity. These peptides were further screened as non-toxic, immunogenic and non-mutated residues of envelop viral protein. The predicted epitope could work as suitable candidate(s) for peptide based vaccine development. Further, experimental validation of these epitopes is warranted to ensure the potential of B- and T-cells stimulation for their efficient use as vaccine candidates, and as diagnostic agents against ZIKV.",2017 Jan 13,"['Janahi, Essam Mohammed', 'Dhasmana, Anupam', 'Srivastava, Vandana', 'Sarangi, Aditya Narayan', 'Raza, Sana', 'Arif, Jamal M.', 'Bhatt, Madan Lal Bramha', 'Lohani, Mohtashim', 'Areeshi, Mohammed Yahya', 'Saxena, Anand Murari', 'Haque, Shafiul']",EXCLI J,,,True
d9d02e04db1c0d620a206b018960427447bfeff6,PMC,"In silico CD4+, CD8+ T-cell and B-cell immunity associated immunogenic epitope prediction and HLA distribution analysis of Zika virus",http://dx.doi.org/10.17179/excli2016-719,PMC5379118,28435428,CC BY,"Zika virus (ZIKV) is a mosquito-borne flavivirus distributed all over Africa, South America and Asia. The infection with the virus may cause acute febrile sickness that clinically resembles dengue fever, yet there is no vaccine, no satisfactory treatment, and no means of evaluating the risk of the disease or prognosis in the infected people. In the present study, the efficacy of the host's immune response in reducing the risk of infectious diseases was taken into account to carry out immuno-informatics driven epitope screening strategy of vaccine candidates against ZIKV. In this study, HLA distribution analysis was done to ensure the coverage of the vast majority of the population. Systematic screening of effective dominant immunogens was done with the help of Immune Epitope & ABCPred databases. The outcomes suggested that the predicted epitopes may be protective immunogens with highly conserved sequences and bear potential to induce both protective neutralizing antibodies, T & B cell responses. A total of 25 CD4+ and 16 CD8+ peptides were screened for T-cell mediated immunity. The predicted epitope ""TGLDFSDLYYLTMNNKHWLV"" was selected as a highly immunogenic epitope for humoral immunity. These peptides were further screened as non-toxic, immunogenic and non-mutated residues of envelop viral protein. The predicted epitope could work as suitable candidate(s) for peptide based vaccine development. Further, experimental validation of these epitopes is warranted to ensure the potential of B- and T-cells stimulation for their efficient use as vaccine candidates, and as diagnostic agents against ZIKV.",2017 Jan 13,"['Janahi, Essam Mohammed', 'Dhasmana, Anupam', 'Srivastava, Vandana', 'Sarangi, Aditya Narayan', 'Raza, Sana', 'Arif, Jamal M.', 'Bhatt, Madan Lal Bramha', 'Lohani, Mohtashim', 'Areeshi, Mohammed Yahya', 'Saxena, Anand Murari', 'Haque, Shafiul']",EXCLI J,,,False
eb2843b666bbd106400ec51a67b584e7731c18d4,PMC,Identification of Novel MAGE-G1-Interacting Partners in Retinoic Acid-Induced P19 Neuronal Differentiation Using SILAC-Based Proteomics,http://dx.doi.org/10.1038/srep44699,PMC5379670,28374796,CC BY,"MAGE-G1 is a protein plays role in the early process of neurogenesis. However, the fundamental roles MAGE-G1 played in neurogenesis have not yet been completely understood. Finding the partners MAGE-G1 interacting with will surely contribute to the function study of MAGE-G1. In this study, using Stable Isotope Labeling by Amino acids in Cell culture-immunoprecipitation quantitative proteomics, we screened the interacting proteins of MAGE-G1 during retinoic acid -induced neuronal differentiation of P19 cells and firstly found that FSCN1 and VIME were potential novel MAGE-G1-interacting proteins. Then, the interaction between overexpressed MAGE-G1 and FSCN1 or VIME was validated by GST-pull down assay in bacteria and by co-immunoprecipitation assay in COS7 cells. Endogenous co-immunoprecipitation assay further confirmed that MAGE-G1 interacted with FSCN1 or VIME in P19 cells after a 6-day retinoic acid-induced neuronal differentiation. Those results provide a functional linkage between MAGE-G1 and FSCN1 or VIME and may facilitate a better understanding of the fundamental aspects of MAGE-G1 during neurogenesis.",2017 Apr 4,"['Liu, Yong', 'Chen, Yujian', 'Lin, Shide', 'Yang, Shuguang', 'Liu, Shaojun']",Sci Rep,,,True
a9aa136fdace9bebef4461ce6f81aa033e74c27a,PMC,Identification of Novel MAGE-G1-Interacting Partners in Retinoic Acid-Induced P19 Neuronal Differentiation Using SILAC-Based Proteomics,http://dx.doi.org/10.1038/srep44699,PMC5379670,28374796,CC BY,"MAGE-G1 is a protein plays role in the early process of neurogenesis. However, the fundamental roles MAGE-G1 played in neurogenesis have not yet been completely understood. Finding the partners MAGE-G1 interacting with will surely contribute to the function study of MAGE-G1. In this study, using Stable Isotope Labeling by Amino acids in Cell culture-immunoprecipitation quantitative proteomics, we screened the interacting proteins of MAGE-G1 during retinoic acid -induced neuronal differentiation of P19 cells and firstly found that FSCN1 and VIME were potential novel MAGE-G1-interacting proteins. Then, the interaction between overexpressed MAGE-G1 and FSCN1 or VIME was validated by GST-pull down assay in bacteria and by co-immunoprecipitation assay in COS7 cells. Endogenous co-immunoprecipitation assay further confirmed that MAGE-G1 interacted with FSCN1 or VIME in P19 cells after a 6-day retinoic acid-induced neuronal differentiation. Those results provide a functional linkage between MAGE-G1 and FSCN1 or VIME and may facilitate a better understanding of the fundamental aspects of MAGE-G1 during neurogenesis.",2017 Apr 4,"['Liu, Yong', 'Chen, Yujian', 'Lin, Shide', 'Yang, Shuguang', 'Liu, Shaojun']",Sci Rep,,,False
ff449311692ce29ca9d598747ab871602adb297f,PMC,iTRAQ-based Proteomic Analysis of Porcine Kidney Epithelial PK15 cells Infected with Pseudorabies virus,http://dx.doi.org/10.1038/srep45922,PMC5379687,28374783,CC BY,"Pseudorabies virus (PRV) is one of the most important pathogens of swine, resulting in severe economic losses to the pig industry. To improve our understanding of the host responses to PRV infection, we applied isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with liquid chromatography-tandem mass spectrometry to quantitatively identify the differentially expressed cellular proteins in PRV-infected PK15 cells. In total, relative quantitative data were identified for 4333 proteins in PRV and mock- infected PK15 cells, among which 466 cellular proteins were differentially expressed, including 234 upregulated proteins and 232 downregulated proteins. Bioinformatics analysis disclosed that most of these differentially expressed proteins were involved in metabolic processes, cellular growth and proliferation, endoplasmic reticulum (ER) stress response, cell adhesion and cytoskeleton. Moreover, expression levels of four representative proteins, beta-catenin, STAT1, GRB2 and PCNA, were further confirmed by western blot analysis. This is the first attempt to analyze the protein profile of PRV-infected PK15 cells using iTRAQ technology, and our findings may provide valuable information to help understand the host response to PRV infection.",2017 Apr 4,"['Yang, Songbai', 'Pei, Yue', 'Zhao, Ayong']",Sci Rep,,,True
f7ab132ca62c4635ff8ab6568da55d035b67575c,PMC,iTRAQ-based Proteomic Analysis of Porcine Kidney Epithelial PK15 cells Infected with Pseudorabies virus,http://dx.doi.org/10.1038/srep45922,PMC5379687,28374783,CC BY,"Pseudorabies virus (PRV) is one of the most important pathogens of swine, resulting in severe economic losses to the pig industry. To improve our understanding of the host responses to PRV infection, we applied isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with liquid chromatography-tandem mass spectrometry to quantitatively identify the differentially expressed cellular proteins in PRV-infected PK15 cells. In total, relative quantitative data were identified for 4333 proteins in PRV and mock- infected PK15 cells, among which 466 cellular proteins were differentially expressed, including 234 upregulated proteins and 232 downregulated proteins. Bioinformatics analysis disclosed that most of these differentially expressed proteins were involved in metabolic processes, cellular growth and proliferation, endoplasmic reticulum (ER) stress response, cell adhesion and cytoskeleton. Moreover, expression levels of four representative proteins, beta-catenin, STAT1, GRB2 and PCNA, were further confirmed by western blot analysis. This is the first attempt to analyze the protein profile of PRV-infected PK15 cells using iTRAQ technology, and our findings may provide valuable information to help understand the host response to PRV infection.",2017 Apr 4,"['Yang, Songbai', 'Pei, Yue', 'Zhao, Ayong']",Sci Rep,,,False
965d0f74c85dad6e4119bee49d3026fbb91c80b7,PMC,Influenza A H5N1 and H7N9 in China: A spatial risk analysis,http://dx.doi.org/10.1371/journal.pone.0174980,PMC5380336,28376125,CC BY,"BACKGROUND: Zoonotic avian influenza poses a major risk to China, and other parts of the world. H5N1 has remained endemic in China and globally for nearly two decades, and in 2013, a novel zoonotic influenza A subtype H7N9 emerged in China. This study aimed to improve upon our current understanding of the spreading mechanisms of H7N9 and H5N1 by generating spatial risk profiles for each of the two virus subtypes across mainland China. METHODS AND FINDINGS: In this study, we (i) developed a refined data set of H5N1 and H7N9 locations with consideration of animal/animal environment case data, as well as spatial accuracy and precision; (ii) used this data set along with environmental variables to build species distribution models (SDMs) for each virus subtype in high resolution spatial units of 1km(2) cells using Maxent; (iii) developed a risk modelling framework which integrated the results from the SDMs with human and chicken population variables, which was done to quantify the risk of zoonotic transmission; and (iv) identified areas at high risk of H5N1 and H7N9 transmission. We produced high performing SDMs (6 of 8 models with AUC > 0.9) for both H5N1 and H7N9. In all our SDMs, H7N9 consistently showed higher AUC results compared to H5N1, suggesting H7N9 suitability could be better explained by environmental variables. For both subtypes, high risk areas were primarily located in south-eastern China, with H5N1 distributions found to be more diffuse and extending more inland compared to H7N9. CONCLUSIONS: We provide projections of our risk models to public health policy makers so that specific high risk areas can be targeted for control measures. We recommend comparing H5N1 and H7N9 prevalence rates and survivability in the natural environment to better understand the role of animal and environmental transmission in human infections.",2017 Apr 4,"['Bui, Chau Minh', 'Gardner, Lauren', 'MacIntyre, Raina', 'Sarkar, Sahotra']",PLoS One,,,True
e8f4d22d624e8deec9597ce88e53b1751386cd1d,PMC,Estimation of Time-Dependent Reproduction Numbers for Porcine Reproductive and Respiratory Syndrome across Different Regions and Production Systems of the US,http://dx.doi.org/10.3389/fvets.2017.00046,PMC5380673,28424778,CC BY,"Porcine reproductive and respiratory syndrome (PRRS) is, arguably, the most impactful disease for the North American swine industry, due to its known considerable economic losses. The Swine Health Monitoring Project (SHMP) monitors and reports weekly new PRRS cases in 766 sow herds across the US. The time-dependent reproduction number (TD-R) is a measure of a pathogen’s transmissibility. It may serve to capture and report PRRS virus (PRRSV) spread at the regional and system levels. The primary objective of the study here was to estimate the TD-R values for PRRSV using regional and system-level PRRS data, and to contrast it with commonly used metrics of disease, such as incidence estimates and space–time clusters. The second objective was to test whether the estimated TD-Rs were homogenous across four US regions. Retrospective monthly incidence data (2009–2016) were available from the SHMP. The dataset was divided into four regions based on location of participants, and demographic and environmental features, namely, South East (North Carolina), Upper Midwest East (UME, Minnesota/Iowa), Upper Midwest West (Nebraska/South Dakota), and South (Oklahoma panhandle). Generation time distributions were fit to incidence data for each region, and used to calculate the TD-Rs. The Kruskal–Wallis test was used to determine whether the median TD-Rs differed across the four areas. Furthermore, we used a space–time permutation model to assess spatial–temporal patterns for the four regions. Results showed TD-Rs were right skewed with median values close to “1” across all regions, confirming that PRRS has an overall endemic nature. Variation in the TD-R patterns was noted across regions and production systems. Statistically significant periods of PRRSV spread (TD-R > 1) were identified for all regions except UME. A minimum of three space–time clusters were detected for all regions considering the time period examined herein; and their overlap with “spreader events” identified by the TD-R method varied according to region. TD-Rs may help to measure PRRS spread to understand, in quantitative terms, disease spread, and, ultimately, support the design, implementation, and monitoring of interventions aimed at mitigating the impact of PRRSV spread in the US.",2017 Apr 5,"['Arruda, Andréia G.', 'Alkhamis, Moh A.', 'VanderWaal, Kimberly', 'Morrison, Robert B.', 'Perez, Andres M.']",Front Vet Sci,,,True
d90b2c4decfc17d7349325f437a9ab6082742c24,PMC,Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/mBio.00373-17,PMC5380844,28377531,CC BY,"The evolutionary origins of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) are unknown. Current evidence suggests that insectivorous bats are likely to be the original source, as several 2c CoVs have been described from various species in the family Vespertilionidae. Here, we describe a MERS-like CoV identified from a Pipistrellus cf. hesperidus bat sampled in Uganda (strain PREDICT/PDF-2180), further supporting the hypothesis that bats are the evolutionary source of MERS-CoV. Phylogenetic analysis showed that PREDICT/PDF-2180 is closely related to MERS-CoV across much of its genome, consistent with a common ancestry; however, the spike protein was highly divergent (46% amino acid identity), suggesting that the two viruses may have different receptor binding properties. Indeed, several amino acid substitutions were identified in key binding residues that were predicted to block PREDICT/PDF-2180 from attaching to the MERS-CoV DPP4 receptor. To experimentally test this hypothesis, an infectious MERS-CoV clone expressing the PREDICT/PDF-2180 spike protein was generated. Recombinant viruses derived from the clone were replication competent but unable to spread and establish new infections in Vero cells or primary human airway epithelial cells. Our findings suggest that PREDICT/PDF-2180 is unlikely to pose a zoonotic threat. Recombination in the S1 subunit of the spike gene was identified as the primary mechanism driving variation in the spike phenotype and was likely one of the critical steps in the evolution and emergence of MERS-CoV in humans.",2017 Apr 4,"['Anthony, S. J.', 'Gilardi, K.', 'Menachery, V. D.', 'Goldstein, T.', 'Ssebide, B.', 'Mbabazi, R.', 'Navarrete-Macias, I.', 'Liang, E.', 'Wells, H.', 'Hicks, A.', 'Petrosov, A.', 'Byarugaba, D. K.', 'Debbink, K.', 'Dinnon, K. H.', 'Scobey, T.', 'Randell, S. H.', 'Yount, B. L.', 'Cranfield, M.', 'Johnson, C. K.', 'Baric, R. S.', 'Lipkin, W. I.', 'Mazet, J. A. K.']",mBio,,,True
4e2f13bbb7637dc94eba63f2170cbcbceafcc4c0,PMC,A Fluorometric Method of Measuring Carboxypeptidase Activities for Angiotensin II and Apelin-13,http://dx.doi.org/10.1038/srep45473,PMC5381230,28378780,CC BY,"Degradation of the biologically potent octapeptide angiotensin Ang II-(1-8) is mediated by the activities of several peptidases. The conversion of Ang II to the septapeptide Ang-(1-7) is of particular interest as the latter also confers organ protection. The conversion is catalyzed by angiotensin-converting enzyme 2 and other enzymes that selectively cleave the peptide bond between the proline and the phenylalanine at the carboxyl terminus of Ang II. The contribution of various enzyme activities that collectively lead to the formation of Ang-(1-7) from Ang II, in both normal conditions and in disease states, remains only partially understood. This is largely due to the lack of a reliable and sensitive method to detect these converting activities in complex samples, such as blood and tissues. Here, we report a fluorometric method to measure carboxypeptidase activities that cleave the proline-phenylalanine dipeptide bond in Ang II. This method is also suitable for measuring the conversion of apelin-13. The assay detects the release of phenylalanine amino acid in a reaction with the yeast enzyme of phenylalanine ammonia lyase (PAL). When used in cell and mouse organs, the assay can robustly measure endogenous Ang II and apelin-13-converting activities involved in the renin-angiotensin and the apelinergic systems, respectively.",2017 Apr 5,"['Liu, Pan', 'Wysocki, Jan', 'Serfozo, Peter', 'Ye, Minghao', 'Souma, Tomokazu', 'Batlle, Daniel', 'Jin, Jing']",Sci Rep,,,True
3d53252b41f601cefc47393bb773ca3cfa6f034b,PMC,A Fluorometric Method of Measuring Carboxypeptidase Activities for Angiotensin II and Apelin-13,http://dx.doi.org/10.1038/srep45473,PMC5381230,28378780,CC BY,"Degradation of the biologically potent octapeptide angiotensin Ang II-(1-8) is mediated by the activities of several peptidases. The conversion of Ang II to the septapeptide Ang-(1-7) is of particular interest as the latter also confers organ protection. The conversion is catalyzed by angiotensin-converting enzyme 2 and other enzymes that selectively cleave the peptide bond between the proline and the phenylalanine at the carboxyl terminus of Ang II. The contribution of various enzyme activities that collectively lead to the formation of Ang-(1-7) from Ang II, in both normal conditions and in disease states, remains only partially understood. This is largely due to the lack of a reliable and sensitive method to detect these converting activities in complex samples, such as blood and tissues. Here, we report a fluorometric method to measure carboxypeptidase activities that cleave the proline-phenylalanine dipeptide bond in Ang II. This method is also suitable for measuring the conversion of apelin-13. The assay detects the release of phenylalanine amino acid in a reaction with the yeast enzyme of phenylalanine ammonia lyase (PAL). When used in cell and mouse organs, the assay can robustly measure endogenous Ang II and apelin-13-converting activities involved in the renin-angiotensin and the apelinergic systems, respectively.",2017 Apr 5,"['Liu, Pan', 'Wysocki, Jan', 'Serfozo, Peter', 'Ye, Minghao', 'Souma, Tomokazu', 'Batlle, Daniel', 'Jin, Jing']",Sci Rep,,,False
610cdf0a90ee7272f51c5531375a7355768f865a,PMC,Non-canonical Translation in Plant RNA Viruses,http://dx.doi.org/10.3389/fpls.2017.00494,PMC5382211,28428795,CC BY,"Viral protein synthesis is completely dependent upon the host cell's translational machinery. Canonical translation of host mRNAs depends on structural elements such as the 5′ cap structure and/or the 3′ poly(A) tail of the mRNAs. Although many viral mRNAs are devoid of one or both of these structures, they can still translate efficiently using non-canonical mechanisms. Here, we review the tools utilized by positive-sense single-stranded (+ss) RNA plant viruses to initiate non-canonical translation, focusing on cis-acting sequences present in viral mRNAs. We highlight how these elements may interact with host translation factors and speculate on their contribution for achieving translational control. We also describe other translation strategies used by plant viruses to optimize the usage of the coding capacity of their very compact genomes, including leaky scanning initiation, ribosomal frameshifting and stop-codon readthrough. Finally, future research perspectives on the unusual translational strategies of +ssRNA viruses are discussed, including parallelisms between viral and host mRNAs mechanisms of translation, particularly for host mRNAs which are translated under stress conditions.",2017 Apr 6,"['Miras, Manuel', 'Miller, W. Allen', 'Truniger, Verónica', 'Aranda, Miguel A.']",Front Plant Sci,,,True
9663f9f18256ca7161c2af2ce451911c90f629da,PMC,Decreased Levels of Foldase and Chaperone Proteins Are Associated with an Early-Onset Amyotrophic Lateral Sclerosis,http://dx.doi.org/10.3389/fnmol.2017.00099,PMC5382314,28428745,CC BY,"Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive upper and lower motor neuron degeneration. One of the peculiar clinical characteristics of ALS is the wide distribution in age of onset, which is probably caused by different combinations of intrinsic and exogenous factors. We investigated whether these modifying factors are converging into common pathogenic pathways leading either to an early or a late disease onset. This would imply the identification of phenotypic biomarkers, that can distinguish the two populations of ALS patients, and of relevant pathways to consider in a therapeutic intervention. Toward this aim a differential proteomic analysis was performed in peripheral blood mononuclear cells (PBMC) from a group of 16 ALS patients with an age of onset ≤55 years and a group of 16 ALS patients with an age of onset ≥75 years, and matched healthy controls. We identified 43 differentially expressed proteins in the two groups of patients. Gene ontology analysis revealed that there was a significant enrichment in annotations associated with protein folding and response to stress. We next validated a selected number of proteins belonging to this functional group in 85 patients and 83 age- and sex-matched healthy controls using immunoassays. The results of the validation study confirmed that there was a decreased level of peptidyl-prolyl cis-trans isomerase A (also known as cyclophilin A), heat shock protein HSP 90-alpha, 78 kDa glucose-regulated protein (also known as BiP) and protein deglycase DJ-1 in PBMC of ALS patients with an early onset. Similar results were obtained in PBMC and spinal cord from two SOD1(G93A) mouse models with an early and late disease onset. This study suggests that a different ability to upregulate proteins involved in proteostasis, such as foldase and chaperone proteins, may be at the basis of a different susceptibility to ALS, putting forward the development of therapeutic approaches aiming at boosting the protein quality control system.",2017 Apr 6,"['Filareti, Melania', 'Luotti, Silvia', 'Pasetto, Laura', 'Pignataro, Mauro', 'Paolella, Katia', 'Messina, Paolo', 'Pupillo, Elisabetta', 'Filosto, Massimiliano', 'Lunetta, Christian', 'Mandrioli, Jessica', 'Fuda, Giuseppe', 'Calvo, Andrea', 'Chiò, Adriano', 'Corbo, Massimo', 'Bendotti, Caterina', 'Beghi, Ettore', 'Bonetto, Valentina']",Front Mol Neurosci,,,False
2dd6dd3a860b840098976e99c1124ea89466e77c,PMC,Decreased Levels of Foldase and Chaperone Proteins Are Associated with an Early-Onset Amyotrophic Lateral Sclerosis,http://dx.doi.org/10.3389/fnmol.2017.00099,PMC5382314,28428745,CC BY,"Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive upper and lower motor neuron degeneration. One of the peculiar clinical characteristics of ALS is the wide distribution in age of onset, which is probably caused by different combinations of intrinsic and exogenous factors. We investigated whether these modifying factors are converging into common pathogenic pathways leading either to an early or a late disease onset. This would imply the identification of phenotypic biomarkers, that can distinguish the two populations of ALS patients, and of relevant pathways to consider in a therapeutic intervention. Toward this aim a differential proteomic analysis was performed in peripheral blood mononuclear cells (PBMC) from a group of 16 ALS patients with an age of onset ≤55 years and a group of 16 ALS patients with an age of onset ≥75 years, and matched healthy controls. We identified 43 differentially expressed proteins in the two groups of patients. Gene ontology analysis revealed that there was a significant enrichment in annotations associated with protein folding and response to stress. We next validated a selected number of proteins belonging to this functional group in 85 patients and 83 age- and sex-matched healthy controls using immunoassays. The results of the validation study confirmed that there was a decreased level of peptidyl-prolyl cis-trans isomerase A (also known as cyclophilin A), heat shock protein HSP 90-alpha, 78 kDa glucose-regulated protein (also known as BiP) and protein deglycase DJ-1 in PBMC of ALS patients with an early onset. Similar results were obtained in PBMC and spinal cord from two SOD1(G93A) mouse models with an early and late disease onset. This study suggests that a different ability to upregulate proteins involved in proteostasis, such as foldase and chaperone proteins, may be at the basis of a different susceptibility to ALS, putting forward the development of therapeutic approaches aiming at boosting the protein quality control system.",2017 Apr 6,"['Filareti, Melania', 'Luotti, Silvia', 'Pasetto, Laura', 'Pignataro, Mauro', 'Paolella, Katia', 'Messina, Paolo', 'Pupillo, Elisabetta', 'Filosto, Massimiliano', 'Lunetta, Christian', 'Mandrioli, Jessica', 'Fuda, Giuseppe', 'Calvo, Andrea', 'Chiò, Adriano', 'Corbo, Massimo', 'Bendotti, Caterina', 'Beghi, Ettore', 'Bonetto, Valentina']",Front Mol Neurosci,,,True
83779b8c44857750b3b75b5d83cc3fdbb7441a50,PMC,Porcine epidemic diarrhoea: new insights into an old disease,http://dx.doi.org/10.1186/s40813-015-0007-9,PMC5382377,28405418,CC BY,"Porcine epidemic diarrhea (PED) is an enteric disease in swine caused by an alphacoronavirus. It affects swine of all ages causing acute diarrhoea and can lead to severe dehydration and death in suckling piglets. Being recognized for the first time in Europe and Asia during the seventies and the eighties, respectively, it has remained a relevant cause of diarrhea outbreaks in Asia for years and to the present. It has become a major concern in swine production since 2013 when the virus was detected for first time in the USA and in other American countries causing a high number of pig deaths and significant economic losses. The present review aims at approaching the reader to the state of the art of PED giving answer to some of the most recent questions which have arisen related to this disease.",2015 Sep 29,"['Carvajal, Ana', 'Argüello, Héctor', 'Martínez-Lobo, F. Javier', 'Costillas, Sara', 'Miranda, Rubén', 'G. de Nova, Pedro J.', 'Rubio, Pedro']",Porcine Health Manag,,,True
78a2a00aa8b0a7ab8cf82403e941085830445a5d,PMC,Novel analytic tools for the study of porcine reproductive and respiratory syndrome virus (PRRSv) in endemic settings: lessons learned in the U.S.,http://dx.doi.org/10.1186/s40813-016-0019-0,PMC5382381,28405429,CC BY,"Since its emergence in the late 1980’s, the porcine reproductive and respiratory syndrome virus (PRRSv) has posed a significant challenge to the pig industry worldwide. Since then, a number of epidemiological tools have been created to support control and eventual elimination of the disease at the farm and regional levels. Still, many aspects of the disease dynamics are yet-to-be elucidated, such as what are the economically optimal control strategies at the farm and regional level, what is the role that the voluntary regional control programs may play, how to optimize the use of molecular tools for surveillance and monitoring in infected settings, what is the full impact of the disease in a farm, or what is the relative contribution of alternative transmission routes on the occurrence of PRRSv outbreaks. Here, we summarize a number of projects demonstrating the use of novel analytical tools in the assessment of PRRSv epidemiology in the United States. Results presented demonstrate how quantitative analysis of routinely collected data may help in understanding regional epidemiology of PRRSv and to quantify its full impact, and how the integration of phylodynamic methods as a standard tool for molecular surveillance of PRRSv might help to inform control and prevention strategies in high-risk epidemiological situations. Ultimately, these tools will help to support PRRSv control at farm and regional levels in endemically infected settings.",2016 Jan 21,"['Alvarez, Julio', 'Valdes-Donoso, Pablo', 'Tousignant, Steven', 'Alkhamis, Mohammad', 'Morrison, Robert', 'Perez, Andres']",Porcine Health Manag,,,True
839063ca98beeac93cfb9243045c7d14728420a7,PMC,Modified-live PRRSV subtype 1 vaccine UNISTRAIN(®) PRRS provides a partial clinical and virological protection upon challenge with East European subtype 3 PRRSV strain Lena,http://dx.doi.org/10.1186/s40813-016-0029-y,PMC5382438,28405438,CC BY,"BACKGROUND: Western European porcine reproductive and respiratory syndrome virus (PRRSV) strains cause limited and mild clinical signs whereas more virulent strains are circulating in Eastern Europe. The emergence of such highly virulent strains in Western Europe might result in severe clinical problems and a financial disaster. In this context, the efficacy of the commercial modified-live PRRSV subtype 1 vaccine UNISTRAIN(®) PRRS was tested upon challenge with the East European subtype 3 PRRSV strain Lena. RESULTS: The mean duration of fever was shortened and the number of fever days was significantly lower in vaccinated pigs than in control pigs. Moreover, a lower number of vaccinated animals showed fever, respiratory disorders and conjunctivitis. The mean virus titers in the nasal secretions post challenge (AUC) were significantly lower in the vaccinated group than in the control group. The duration of viremia was slightly shorter (not significantly different) in the vaccinated group as compared to the control group. CONCLUSIONS: Vaccination of pigs with the modified-live vaccine UNISTRAIN(®) PRRS provides a partial clinical and virological protection against the PRRSV subtype 3 strain Lena.",2016 May 9,"['Bonckaert, Caroline', 'van der Meulen, Karen', 'Rodríguez-Ballarà, Isaac', 'Pedrazuela Sanz, Rafael', 'Martinez, Mar Fenech', 'Nauwynck, Hans J.']",Porcine Health Manag,,,True
1d55a99be0e217434aa3a7bfafb4d83c83d12525,PMC,Probability of introducing porcine epidemic diarrhea virus into Danish pig herds by imported spray-dried porcine plasma,http://dx.doi.org/10.1186/s40813-015-0010-1,PMC5382482,28405424,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV) has never been reported in Denmark, but it has been found in Europe, Asia and North America. Ultimately, PEDV has been associated with devastating outbreaks in pig farms. We developed a stochastic simulation model to carry out a quantitative risk assessment and to estimate the annual probability (PPlasma) of introducing PEDV into the Danish pig population, by imported spray-dried porcine plasma (SDPP). The model was based on information from literature and Danish feed companies. Moreover testing the batch of raw blood (before the spray-drying) was considered as potential risk mitigation measure in the future. RESULTS: The median PPlasma was 0.2 % (90 % P.I.: 0.003 %; 2.6 %). Hence, the annual probability of introducing PEDV into the Danish pig population by imported SDPP appeared very low, and on average at least one introduction each 500 years – corresponding to 1/0.002 - could be expected. However, if PEDV survived the spray-drying process and storage was insufficient to completely remove the remaining viable virus (e.g. due to storage at low environmental temperatures during a short time period) the PPlasma was 4.7 % (0.06 %; 57.4 %). In that case, on average, at least one PEDV introduction each 21 years could be expected. This probability could be reduced to 0.3 % (0.004 %; 6.0 %) if the raw batch of blood could be tested before drying (corresponding to at least one introduction each 333 years on average). CONCLUSIONS: This study provides preliminary and important information on the probability of introducing PEDV into the Danish pig population by use of SDPP. Currently PED is not a notifiable disease in the EU and uncertainty was present in our estimates due to possible underreporting in EU Member States, from which SDPP is imported into Denmark. In the future, PED might become a notifiable disease, and in such a case, new knowledge could become available on its epidemiology. Moreover, SDPP could be imported more safely if: producers find a way to substantiate freedom from disease (at least) in herds delivering blood for SDPP, the batch of blood tests negative for PEDV and conditions for processing/storage required by the international laws are respected.",2015 Dec 11,"['Foddai, Alessandro', 'Nielsen, Lisbeth Harm', 'Møgelmose, Vibeke', 'Alban, Lis']",Porcine Health Manag,,,True
13b8c068799a93b4441116bb6cabae222d126d32,PMC,New oligonucleotide microarray for rapid diagnosis of avian viral diseases,http://dx.doi.org/10.1186/s12985-017-0738-0,PMC5382490,28381285,CC BY,"BACKGROUND: We developed a new oligonucleotide microarray comprising 16 identical subarrays for simultaneous rapid detection of avian viruses: avian influenza virus (AIV), Newcastle disease virus (NDV), infection bronchitis virus (IBV), and infectious bursal disease virus (IBDV) in single- and mixed-virus infections. The objective of the study was to develop an oligonucleotide microarray for rapid diagnosis of avian diseases that would be used in the course of mass analysis for routine epidemiological surveillance owing to its ability to test one specimen for several infections. METHODS AND RESULTS: The paper describes the technique for rapid and simultaneous diagnosis of avian diseases such as avian influenza, Newcastle disease, infectious bronchitis and infectious bursal disease with use of oligonucleotide microarray, conditions for hybridization of fluorescent-labelled viral cDNA on the microarray and its specificity tested with use of AIV, NDV, IBV, IBDV strains as well as biomaterials from poultry. Sensitivity and specificity of the developed microarray was evaluated with use of 122 specimens of biological material: 44 cloacal swabs from sick birds and 78 tissue specimens from dead wild and domestic birds, as well as with use of 15 AIV, NDV, IBV and IBDV strains, different in their origin, epidemiological and biological characteristics (RIBSP Microbial Collection). This microarray demonstrates high diagnostic sensitivity (99.16% within 95% CI limits 97.36–100%) and specificity (100%). Specificity of the developed technique was confirmed by direct sequencing of NP and M (AIV), VP2 (IBDV), S1 (IBV), NP (NDV) gene fragments. CONCLUSION: Diagnostic effectiveness of the developed DNA microarray is 99.18% and therefore it can be used in mass survey for specific detection of AIV, NDV, IBV and IBDV circulating in the region in the course of epidemiological surveillance. Rather simple method for rapid diagnosis of avian viral diseases that several times shortens duration of assay versus classical diagnostic methods is proposed.",2017 Apr 5,"['Sultankulova, Kulyaisan T.', 'Kozhabergenov, Nurlan S.', 'Strochkov, Vitaliy M.', 'Burashev, Yerbol D.', 'Shorayeva, Kamshat A.', 'Chervyakova, Olga V.', 'Rametov, Nurkuisa M.', 'Sandybayev, Nurlan T.', 'Sansyzbay, Abylay R.', 'Orynbayev, Mukhit B.']",Virol J,,,True
5646a0eb649cd7e862225225aae1382f8de86f7d,PMC,Feed additives decrease survival of delta coronavirus in nursery pig diets,http://dx.doi.org/10.1186/s40813-016-0048-8,PMC5382497,28405461,CC BY,"BACKGROUND: Feed contaminated with feces from infected pigs is believed to be a potential route of transmission of porcine delta coronavirus (PDCoV). The objective of this study was to determine if the addition of commercial feed additives (e.i., acids, salt and sugar) to swine feed can be an effective strategy to inactive PDCoV. RESULTS: Six commercial feed acids (UltraAcid P, Activate DA, KEMGEST, Acid Booster, Luprosil, and Amasil), salt, and sugar were evaluated. The acids were added at the recommended concentrations to 5 g aliquots of complete feed, which were also inoculated with 1 mL of PDCoV and incubated for 0, 7, 14, 21, 28, and 35 days. In another experiment, double the recommended concentrations of these additives were also added to the feed samples and incubated for 0, 1, 3, 7, and 10 days. All samples were stored at room temperature (~25 °C) followed by removal of aliquots at 0, 7, 14, 21, 28, and 35 days. Any surviving virus was eluted in a buffer solution and then titrated in swine testicular cells. Feed samples without any additive were used as controls. Both Weibull and log-linear kinetic models were used to analyze virus survival curves. The presence of a tail in the virus inactivation curves indicated deviations from the linear behavior and hence, the Weibull model was chosen for characterizing the inactivation responses due to the better fit. At recommended concentrations, delta values (days to decrease virus concentration by 1 log) ranged from 0.62–1.72 days, but there were no differences on virus survival among feed samples with or without additives at the manufacturers recommended concentrations. Doubling the concentration of the additives reduced the delta value to ≤ 0.28 days (P < 0.05) for all the additives except for Amasil (delta values of 0.86 vs. 4.95 days). Feed additives that contained phosphoric acid, citric acid, or fumaric acid were the most effective in reducing virus survival, although none of the additives completely inactivated the virus by 10- days post-inoculation. CONCLUSIONS: Commercial feed additives (acidifiers and salt) may be utilized as a strategy to decrease risk of PDCoV in feed, specially, commercial feed acidifiers at double the recommended concentrations reduced PDCoV survival in complete feed during storage at room temperature. However, none of these additives completely inactivated the virus.",2017 Jan 20,"['Cottingim, Katie M.', 'Verma, Harsha', 'Urriola, Pedro E.', 'Sampedro, Fernando', 'Shurson, Gerald C.', 'Goyal, Sagar M.']",Porcine Health Manag,,,True
d1fd1fafa75ee05827d3e7e916a03ddf159317ea,PMC,Evaluation of biosecurity measures to prevent indirect transmission of porcine epidemic diarrhea virus,http://dx.doi.org/10.1186/s12917-017-1017-4,PMC5382501,28381304,CC BY,"BACKGROUND: The effectiveness of biosecurity methods to mitigate the transmission of porcine epidemic diarrhea virus (PEDV) via farm personnel or contaminated fomites is poorly understood. This study was undertaken to evaluate the effectiveness of biosecurity procedures directed at minimizing transmission via personnel following different biosecurity protocols using a controlled experimental setting. RESULTS: PEDV RNA was detected from rectal swabs of experimentally infected (INF) and sentinel pigs by real-time reverse transcription polymerase chain reaction (rRT-PCR). Virus shedding in INF pigs peaked at 1 day post infection (dpi) and viral RNA levels remained elevated through 19 dpi. Sentinel pigs in the low biosecurity group (LB) became PEDV positive after the first movement of study personnel from the INF group. However, rectal swabs from pigs in the medium biosecurity (MB) and high biosecurity (HB) groups were negative during the 10 consecutive days of movements and remained negative through 24 days post movement (dpm) when the first trial was terminated. Viral RNA was detected at 1 dpm through 3 dpm from the personal protective equipment (PPE) of LB personnel. In addition, at 1 dpm, 2 hair/face swabs from MB personnel were positive; however, transmission of virus was not detected. All swabs of fomite from the HB study personnel were negative. CONCLUSIONS: These results indicate that indirect PEDV transmission through contaminated PPE occurs rapidly (within 24 h) under modeled conditions. Biosecurity procedures such as changing PPE, washing exposed skin areas, or taking a shower are recommended for pig production systems and appear to be an effective option for lowering the risk of PEDV transmission between groups of pigs.",2017 Apr 5,"['Kim, Yonghyan', 'Yang, My', 'Goyal, Sagar M.', 'Cheeran, Maxim C-J.', 'Torremorell, Montserrat']",BMC Vet Res,,,True
5390aefc8bb1a06635a321c0cd82589e2b91c9ee,PMC,Genetic resistance - an alternative for controlling PRRS?,http://dx.doi.org/10.1186/s40813-016-0045-y,PMC5382513,28405453,CC BY,"PRRS is one of the most challenging diseases for world-wide pig production. Attempts for a sustainable control of this scourge by vaccination have not yet fully satisfied. With an increasing knowledge and methodology in disease resistance, a new world-wide endeavour has been started to support the combat of animal diseases, based on the existence of valuable gene variants with regard to any host-pathogen interaction. Several groups have produced a wealth of evidence for natural variability in resistance/susceptibility to PRRS in our commercial breeding lines. However, up to now, exploiting existing variation has failed because of the difficulty to detect the carriers of favourable and unfavourable alleles, especially with regard to such complex polygenic traits like resistance to PRRS. New hope comes from new genomic tools like next generation sequencing which have become extremely fast and low priced. Thus, research is booming world-wide and the jigsaw puzzle is filling up – slowly but steadily. On the other hand, knowledge from virological and biomedical basic research has opened the way for an “intervening way”, i.e. the modification of identified key genes that occupy key positions in PRRS pathogenesis, like CD163. CD163 was identified as the striking receptor in PRRSV entry and its knockout from the genome by gene editing has led to the production of pigs that were completely resistant to PRRSV – a milestone in modern pig breeding. However, at this early step, concerns remain about the acceptance of societies for gene edited products and regulation still awaits upgrading to the new technology. Further questions arise with regard to upcoming patents from an ethical and legal point of view. Eventually, the importance of CD163 for homeostasis, defence and immunity demands for more insight before its complete or partial silencing can be answered. Whatever path will be followed, even a partial abolishment of PRRSV replication will lead to a significant improvement of the disastrous herd situation, with a significant impact on welfare, performance, antimicrobial consumption and consumer protection. Genetics will be part of a future solution.",2016 Nov 16,"Reiner, Gerald",Porcine Health Manag,,,True
2bce7709e22e3d5a110cb77501f6d97db10d9c05,PMC,"Spray dried plasma as an alternative to antibiotics in piglet feeds, mode of action and biosafety",http://dx.doi.org/10.1186/s40813-016-0034-1,PMC5382520,28405442,CC BY,"The use of growth promoting and therapeutic antibiotics in piglet feed has been a concerning subject over the last few decades because of the risk of generating antimicrobial resistance that could be transferred to humans. As a result, many products have been proposed as potential alternatives to the use of antibiotics, and among these, spray dried plasma is considered one of the most promising. However, there have been concerns about its biosafety, particularly during periods of emergence or re-emergence of swine diseases in different regions of the world, such as the recent porcine epidemic diarrhea virus outbreak in North America. The objectives of this paper are to review recent publications about the use of spray dried plasma as an alternative to antibiotics in weaned pig diets, the possible mechanisms of action of spray dried plasma, and the existing evidence related to the biosafety of spray dried animal plasma. Particular attention is given to studies in which spray dried plasma has been directly compared to antibiotics or other alternative antimicrobial products. Several studies on the possible modes of action for spray dried plasma, such as preservation of gut barrier function or modulation of the immune response, are also reviewed. Finally, the paper focuses on the review of the existing studies on the risks of disease transmission with the use of spray dried plasma from porcine origin. Overall, spray dried plasma is a promising alternative to in-feed antimicrobials for piglets, particularly during the early stages of the post-weaning phase. Additionally, there is enough evidence to support that commercial spray dried porcine plasma is a safe product for pigs.",2016 Jul 23,"['Pérez-Bosque, Anna', 'Polo, Javier', 'Torrallardona, David']",Porcine Health Manag,,,True
626347808e0ebaed5176f6a00206c35e48aeb90d,PMC,Genome structure and transcriptional regulation of human coronavirus NL63,http://dx.doi.org/10.1186/1743-422X-1-7,PMC538260,15548333,CC BY,"BACKGROUND: Two human coronaviruses are known since the 1960s: HCoV-229E and HCoV-OC43. SARS-CoV was discovered in the early spring of 2003, followed by the identification of HCoV-NL63, the fourth member of the coronaviridae family that infects humans. In this study, we describe the genome structure and the transcription strategy of HCoV-NL63 by experimental analysis of the viral subgenomic mRNAs. RESULTS: The genome of HCoV-NL63 has the following gene order: 1a-1b-S-ORF3-E-M-N. The GC content of the HCoV-NL63 genome is extremely low (34%) compared to other coronaviruses, and we therefore performed additional analysis of the nucleotide composition. Overall, the RNA genome is very low in C and high in U, and this is also reflected in the codon usage. Inspection of the nucleotide composition along the genome indicates that the C-count increases significantly in the last one-third of the genome at the expense of U and G. We document the production of subgenomic (sg) mRNAs coding for the S, ORF3, E, M and N proteins. We did not detect any additional sg mRNA. Furthermore, we sequenced the 5' end of all sg mRNAs, confirming the presence of an identical leader sequence in each sg mRNA. Northern blot analysis indicated that the expression level among the sg mRNAs differs significantly, with the sg mRNA encoding nucleocapsid (N) being the most abundant. CONCLUSIONS: The presented data give insight into the viral evolution and mutational patterns in coronaviral genome. Furthermore our data show that HCoV-NL63 employs the discontinuous replication strategy with generation of subgenomic mRNAs during the (-) strand synthesis. Because HCoV-NL63 has a low pathogenicity and is able to grow easily in cell culture, this virus can be a powerful tool to study SARS coronavirus pathogenesis.",2004 Nov 17,"['Pyrc, Krzysztof', 'Jebbink, Maarten F', 'Berkhout, Ben', 'van der Hoek, Lia']",Virol J,,,True
b92be96a5b5d040400b1eed4feff463fd3505b3b,PMC,Socio-environmental exposures and health outcomes among persons with sickle cell disease,http://dx.doi.org/10.1371/journal.pone.0175260,PMC5383275,28384224,CC BY,"There is much variability in the expression of sickle cell disease (SCD) and recent works suggest that environmental and social factors may also influence this variability. This paper aims to use geographic information systems technology to examine the association between socio-environmental exposures and health outcomes in all persons who have attended or currently attend the Sickle Cell Unit in Jamaica. Rural patients presented for clinical care at older ages and had less annual visits to clinic. Persons travelled relatively long distances to seek SCD care and those travelling longer had less health maintenance visits. Urban patients had a higher prevalence of significant pain crises (69.4% vs. 55.8%, p value<0.001) and respiratory events (21.2% vs. 14%, p value<0.001). Prevalence of leg ulcers did not vary between rural and urban patients but was higher in males than in females. Females also had lower odds of having respiratory events but there was no sex difference in history of painful crises. Persons with more severe genotypes lived in higher poverty and travelled longer for healthcare services. Persons in areas with higher annual rainfall, higher mean temperatures and living farther from factories had less painful crises and respiratory events. The paper highlights a need for better access to healthcare services for Jamaicans with SCD especially in rural areas of the island. It also reports interesting associations between environmental climatic exposures and health outcomes.",2017 Apr 6,"['Asnani, Monika R.', 'Knight Madden, Jennifer', 'Reid, Marvin', 'Greene, Lisa-Gaye', 'Lyew-Ayee, Parris']",PLoS One,,,True
ebd781f1bacf68fbaa6efa2aff4390c20a405999,PMC,Expression profiles of immune mediators in feline Coronavirus-infected cells and clinical samples of feline Coronavirus-positive cats,http://dx.doi.org/10.1186/s12917-017-1019-2,PMC5384144,28388950,CC BY,"BACKGROUND: There are two biotypes of feline coronavirus (FCoV): the self-limiting feline enteric coronavirus (FECV) and the feline infectious peritonitis virus (FIPV), which causes feline infectious peritonitis (FIP), a fatal disease associated with cats living in multi-cat environments. This study provides an insight on the various immune mediators detected in FCoV-positive cats which may be responsible for the development of FIP. RESULTS: In this study, using real-time PCR and multiplex bead-based immunoassay, the expression profiles of several immune mediators were examined in Crandell-Reese feline kidney (CRFK) cells infected with the feline coronavirus (FCoV) strain FIPV 79–1146 and in samples obtained from FCoV-positive cats. CRFK cells infected with FIPV 79–1146 showed an increase in the expression of interferon-related genes and pro-inflammatory cytokines such as MX1, viperin, CXCL10, CCL8, RANTES, KC, MCP1, and IL8. In addition, an increase in the expression of the above cytokines as well as GM-CSF and IFNγ was also detected in the PBMC, serum, and peritoneal effusions of FCoV-positive cats. Although the expression of MX1 and viperin genes was variable between cats, the expression of these two genes was relatively higher in cats having peritoneal effusion compared to cats without clinically obvious effusion. Higher viral load was also detected in the supernatant of peritoneal effusions compared to in the plasma of FCoV-positive cats. As expected, the secretion of IL1β, IL6 and TNFα was readily detected in the supernatant of peritoneal effusions of the FCoV-positive cats. CONCLUSIONS: This study has identified various pro-inflammatory cytokines and interferon-related genes such as MX1, viperin, CXCL10, CCL8, RANTES, KC, MCP1, IL8, GM-CSF and IFNγ in FCoV-positive cats. With the exception of MX1 and viperin, no distinct pattern of immune mediators was observed that distinguished between FCoV-positive cats with and without peritoneal effusion. Further studies based on definitive diagnosis of FIP need to be performed to confirm the clinical importance of this study.",2017 Apr 7,"['Safi, Nikoo', 'Haghani, Amin', 'Ng, Shing Wei', 'Selvarajah, Gayathri Thevi', 'Mustaffa-Kamal, Farina', 'Omar, Abdul Rahman']",BMC Vet Res,,,True
af4389942bc90f030be76a193485be1b0c138cc0,PMC,Emotional crisis in a naturalistic context: characterizing outpatient profiles and treatment effectiveness,http://dx.doi.org/10.1186/s12888-017-1293-3,PMC5384152,28388881,CC BY,"BACKGROUND: Crisis happens daily yet its understanding is often limited, even in the field of psychiatry. Indeed, a challenge is to assess the potential for change of patients so as to offer appropriate therapeutic interventions and enhance treatment program efficacy. This naturalistic study aimed to identify the socio-demographical characteristics and clinical profiles at admission of patients referred to a specialized Crisis Intervention Center (CIC) and to examine the effectiveness of the intervention. METHOD: The sample was composed of 352 adult outpatients recruited among the referrals to the CIC. Assessment completed at admission and at discharge examined psychiatric symptoms, defense mechanisms, recovery styles and global functioning. The crisis intervention consisted in a psychodynamically oriented multimodal approach associated with medication. RESULTS: Regarding the clinical profiles at intake, patients were middle-aged (M = 38.56, SD = 10.91), with a higher proportion of women (62.22%). They were addressed to the CIC because they had attempted to commit suicide or had suicidal ideation or presented depressed mood related to interpersonal difficulties. No statistical differences were found between patients dropping out (n = 215) and those attending the crisis intervention (n = 137). Crisis intervention demonstrated a beneficial effect (p < 0.01) on almost all variables, with Effect Sizes (ES) ranging from small to large (0.12 < ES < 0.75; median = 0.49). However, the Reliable Change Index indicated that most of the issues fall into the undetermined category (range 41.46 to 96.35%; median = 66.20%). CONCLUSIONS: This study establishes the profile of patients referred to the CIC and shows that more than half of the patients dropped out from the crisis intervention before completion. Our findings suggest that people presenting an emotional crisis benefit from crisis intervention. However, given methodological constraints, these results need to be considered with caution. Moreover, the clinical significance of the improvements is not confirmed. Thus, the effectiveness of crisis intervention in naturalistic context is not fully determined and should be more rigorously studied in future research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12888-017-1293-3) contains supplementary material, which is available to authorized users.",2017 Apr 7,"['Zanello, Adriano', 'Berthoud, Laurent', 'Bacchetta, Jean-Pierre']",BMC Psychiatry,,,True
5ca36a454b447db9cb215c7bbb13f8cd1d6ff3e3,PMC,Proof-of-concept study: profile of circulating microRNAs in Bovine serum harvested during acute and persistent FMDV infection,http://dx.doi.org/10.1186/s12985-017-0743-3,PMC5384155,28388926,CC BY,"BACKGROUND: Changes in the levels of circulating microRNAs (miRNAs) in the serum of humans and animals have been detected as a result of infection with a variety of viruses. However, to date, such a miRNA profiling study has not been conducted for foot-and-mouth disease virus (FMDV) infection. METHODS: The relative abundance of 169 miRNAs was measured in bovine serum collected at three different phases of FMDV infection in a proof-of-concept study using miRNA PCR array plates. RESULTS: Alterations in specific miRNA levels were detected in serum during acute, persistent, and convalescent phases of FMDV infection. Subclinical FMDV persistence produced a circulating miRNA profile distinct from cattle that had cleared infection. bta-miR-17-5p was highest expressed during acute infection, whereas bta-miR-31 was the highest during FMDV persistence. Interestingly, miR-1281was significantly down-regulated during both acute and persistent infection. Cattle that cleared infection resembled the baseline profile, adding support to applying serum miRNA profiling for identification of sub-clinically infected FMDV carriers. Significantly regulated miRNAs during acute or persistent infection were associated with cellular proliferation, apoptosis, modulation of the immune response, and lipid metabolism. CONCLUSIONS: These findings suggest a role for non-coding regulatory RNAs in FMDV infection of cattle. Future studies will delineate the individual contributions of the reported miRNAs to FMDV replication, determine if this miRNA signature is applicable across all FMDV serotypes, and may facilitate development of novel diagnostic applications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-017-0743-3) contains supplementary material, which is available to authorized users.",2017 Apr 7,"['Stenfeldt, Carolina', 'Arzt, Jonathan', 'Smoliga, George', 'LaRocco, Michael', 'Gutkoska, Joseph', 'Lawrence, Paul']",Virol J,,,True
0b7581ab8ae5da78a11692b4c7d9399ec6dea283,PMC,Mycoplasma detection by triplex real-time PCR in bronchoalveolar lavage fluid from bovine respiratory disease complex cases,http://dx.doi.org/10.1186/s12917-017-1023-6,PMC5385097,28390431,CC BY,"BACKGROUND: In this study we evaluated the RespoCheck Mycoplasma triplex real-time PCR for the detection in bronchoalveolar lavage fluid (BALF) of Mycoplasma (M.) dispar, M. bovis and M. bovirhinis, all three associated with bovine respiratory disease (BRD). Primers and probes of the RespoCheck Mycoplasma triplex real-time PCR are based on the V3/V4 region of the 16S rRNA gene of the three Mycoplasma species. RESULTS: The analytical sensitivity of the RespoCheck triplex real-time PCR was, as determined by spiking experiments of the Mycoplasma strains in Phosphate Buffered Saline, 300 colony forming units (cfu)/mL for M. dispar, and 30 cfu/mL for M. bovis or M. bovirhinis. The analytical sensitivity of the RespoCheck Mycoplasma triplex real-time PCRwas, as determined on purified DNA, 10 fg DNA per assay for M. dispar and 100 fg fo rM. bovis and M. bovirhinis. The analytical specificity of the RespoCheck Mycoplasma triplex real-time PCR was, as determined by testing Mycoplasmas strains (n = 17) and other bacterial strains (n = 107), 100, 98.2 and 99.1% for M. bovis, M. dispar and M. bovirhinis respectively. The RespoCheck Mycoplasma triplex real-time PCR was compared with the PCR/DGGE analysis for M. bovis, M. dispar and M. bovirhinis respectively by testing 44 BALF samples from calves. CONCLUSION: In conclusion, the RespoCheck PCR assay can be a valuable tool for timely and accurate detection of three Mycoplasma species associated with in bovine respiratory disease.",2017 Apr 8,"['Cornelissen, Jan B. W. J.', 'de Bree, Freddy M.', 'van der Wal, Fimme J.', 'Kooi, Engbert A.', 'Koene, Miriam G. J.', 'Bossers, Alex', 'Smid, Bregtje', 'Antonis, Adriaan F.', 'Wisselink, Henk J.']",BMC Vet Res,,,True
306840cf9baaaf3a2e493a39f3ebd67529b8cb2a,PMC,Allosteric inhibition of aminopeptidase N functions related to tumor growth and virus infection,http://dx.doi.org/10.1038/srep46045,PMC5385526,28393915,CC BY,"Cell surface aminopeptidase N (APN) is a membrane-bound ectoenzyme that hydrolyzes proteins and peptides and regulates numerous cell functions. APN participates in tumor cell expansion and motility, and is a target for cancer therapies. Small drugs that bind to the APN active site inhibit catalysis and suppress tumor growth. APN is also a major cell entry receptor for coronavirus, which binds to a region distant from the active site. Three crystal structures that we determined of human and pig APN ectodomains defined the dynamic conformation of the protein. These structures offered snapshots of closed, intermediate and open APN, which represent distinct functional states. Coronavirus envelope proteins specifically recognized the open APN form, prevented ectodomain progression to the closed form and substrate hydrolysis. In addition, drugs that bind the active site inhibited both coronavirus binding to cell surface APN and infection; the drugs probably hindered APN transition to the virus-specific open form. We conclude that allosteric inhibition of APN functions occurs by ligand suppression of ectodomain motions necessary for catalysis and virus cell entry, as validated by locking APN with disulfides. Blocking APN dynamics can thus be a valuable approach to development of drugs that target this ectoenzyme.",2017 Apr 10,"['Santiago, César', 'Mudgal, Gaurav', 'Reguera, Juan', 'Recacha, Rosario', 'Albrecht, Sébastien', 'Enjuanes, Luis', 'Casasnovas, José M.']",Sci Rep,,,True
bc0838ae0983db0de5f8edd6dc7f5c03f981c359,PMC,Allosteric inhibition of aminopeptidase N functions related to tumor growth and virus infection,http://dx.doi.org/10.1038/srep46045,PMC5385526,28393915,CC BY,"Cell surface aminopeptidase N (APN) is a membrane-bound ectoenzyme that hydrolyzes proteins and peptides and regulates numerous cell functions. APN participates in tumor cell expansion and motility, and is a target for cancer therapies. Small drugs that bind to the APN active site inhibit catalysis and suppress tumor growth. APN is also a major cell entry receptor for coronavirus, which binds to a region distant from the active site. Three crystal structures that we determined of human and pig APN ectodomains defined the dynamic conformation of the protein. These structures offered snapshots of closed, intermediate and open APN, which represent distinct functional states. Coronavirus envelope proteins specifically recognized the open APN form, prevented ectodomain progression to the closed form and substrate hydrolysis. In addition, drugs that bind the active site inhibited both coronavirus binding to cell surface APN and infection; the drugs probably hindered APN transition to the virus-specific open form. We conclude that allosteric inhibition of APN functions occurs by ligand suppression of ectodomain motions necessary for catalysis and virus cell entry, as validated by locking APN with disulfides. Blocking APN dynamics can thus be a valuable approach to development of drugs that target this ectoenzyme.",2017 Apr 10,"['Santiago, César', 'Mudgal, Gaurav', 'Reguera, Juan', 'Recacha, Rosario', 'Albrecht, Sébastien', 'Enjuanes, Luis', 'Casasnovas, José M.']",Sci Rep,,,False
b83417aceefa21bf06ba89462781ebe07142a259,PMC,Homologous recombination is a force in the evolution of canine distemper virus,http://dx.doi.org/10.1371/journal.pone.0175416,PMC5386261,28394936,CC BY,"Canine distemper virus (CDV) is the causative agent of canine distemper (CD) that is a highly contagious, lethal, multisystemic viral disease of receptive carnivores. The prevalence of CDV is a major concern in susceptible animals. Presently, it is unclear whether intragenic recombination can contribute to gene mutations and segment reassortment in the virus. In this study, 25 full-length CDV genome sequences were subjected to phylogenetic and recombinational analyses. The results of phylogenetic analysis, intragenic recombination, and nucleotide selection pressure indicated that mutation and recombination occurred in the six individual genes segment (H, F, P, N, L, M) of the CDV genome. The analysis also revealed pronounced genetic diversity in the CDV genome according to the geographically distinct lineages (genotypes), namely Asia-1, Asia-2, Asia-3, Europe, America-1, and America-2. The six recombination events were detected using SimPlot and RDP programs. The analysis of selection pressure demonstrated that a majority of the nucleotides in the CDV individual gene were under negative selection. Collectively, these data suggested that homologous recombination acts as a key force driving the genetic diversity and evolution of canine distemper virus.",2017 Apr 10,"['Yuan, Chaowen', 'Liu, Wenxin', 'Wang, Yingbo', 'Hou, Jinlong', 'Zhang, Liguo', 'Wang, Guoqing']",PLoS One,,,True
5ac10a9b15162482ce6936829201e0f6d08fb441,PMC,The NF-κB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells,http://dx.doi.org/10.1371/journal.ppat.1006286,PMC5386326,28355270,CC BY,"Coronavirus replication takes place in the host cell cytoplasm and triggers inflammatory gene expression by poorly characterized mechanisms. To obtain more insight into the signals and molecular events that coordinate global host responses in the nucleus of coronavirus-infected cells, first, transcriptome dynamics was studied in human coronavirus 229E (HCoV-229E)-infected A549 and HuH7 cells, respectively, revealing a core signature of upregulated genes in these cells. Compared to treatment with the prototypical inflammatory cytokine interleukin(IL)-1, HCoV-229E replication was found to attenuate the inducible activity of the transcription factor (TF) NF-κB and to restrict the nuclear concentration of NF-κB subunits by (i) an unusual mechanism involving partial degradation of IKKβ, NEMO and IκBα and (ii) upregulation of TNFAIP3 (A20), although constitutive IKK activity and basal TNFAIP3 expression levels were shown to be required for efficient virus replication. Second, we characterized actively transcribed genomic regions and enhancers in HCoV-229E-infected cells and systematically correlated the genome-wide gene expression changes with the recruitment of Ser5-phosphorylated RNA polymerase II and prototypical histone modifications (H3K9ac, H3K36ac, H4K5ac, H3K27ac, H3K4me1). The data revealed that, in HCoV-infected (but not IL-1-treated) cells, an extensive set of genes was activated without inducible p65 NF-κB being recruited. Furthermore, both HCoV-229E replication and IL-1 were shown to upregulate a small set of genes encoding immunomodulatory factors that bind p65 at promoters and require IKKβ activity and p65 for expression. Also, HCoV-229E and IL-1 activated a common set of 440 p65-bound enhancers that differed from another 992 HCoV-229E-specific enhancer regions by distinct TF-binding motif combinations. Taken together, the study shows that cytoplasmic RNA viruses fine-tune NF-κB signaling at multiple levels and profoundly reprogram the host cellular chromatin landscape, thereby orchestrating the timely coordinated expression of genes involved in multiple signaling, immunoregulatory and metabolic processes.",2017 Mar 29,"['Poppe, Michael', 'Wittig, Sascha', 'Jurida, Liane', 'Bartkuhn, Marek', 'Wilhelm, Jochen', 'Müller, Helmut', 'Beuerlein, Knut', 'Karl, Nadja', 'Bhuju, Sabin', 'Ziebuhr, John', 'Schmitz, M. Lienhard', 'Kracht, Michael']",PLoS Pathog,,,True
c23b18fc16e216774e32f7dde9eebc8756194626,PMC,The NF-κB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells,http://dx.doi.org/10.1371/journal.ppat.1006286,PMC5386326,28355270,CC BY,"Coronavirus replication takes place in the host cell cytoplasm and triggers inflammatory gene expression by poorly characterized mechanisms. To obtain more insight into the signals and molecular events that coordinate global host responses in the nucleus of coronavirus-infected cells, first, transcriptome dynamics was studied in human coronavirus 229E (HCoV-229E)-infected A549 and HuH7 cells, respectively, revealing a core signature of upregulated genes in these cells. Compared to treatment with the prototypical inflammatory cytokine interleukin(IL)-1, HCoV-229E replication was found to attenuate the inducible activity of the transcription factor (TF) NF-κB and to restrict the nuclear concentration of NF-κB subunits by (i) an unusual mechanism involving partial degradation of IKKβ, NEMO and IκBα and (ii) upregulation of TNFAIP3 (A20), although constitutive IKK activity and basal TNFAIP3 expression levels were shown to be required for efficient virus replication. Second, we characterized actively transcribed genomic regions and enhancers in HCoV-229E-infected cells and systematically correlated the genome-wide gene expression changes with the recruitment of Ser5-phosphorylated RNA polymerase II and prototypical histone modifications (H3K9ac, H3K36ac, H4K5ac, H3K27ac, H3K4me1). The data revealed that, in HCoV-infected (but not IL-1-treated) cells, an extensive set of genes was activated without inducible p65 NF-κB being recruited. Furthermore, both HCoV-229E replication and IL-1 were shown to upregulate a small set of genes encoding immunomodulatory factors that bind p65 at promoters and require IKKβ activity and p65 for expression. Also, HCoV-229E and IL-1 activated a common set of 440 p65-bound enhancers that differed from another 992 HCoV-229E-specific enhancer regions by distinct TF-binding motif combinations. Taken together, the study shows that cytoplasmic RNA viruses fine-tune NF-κB signaling at multiple levels and profoundly reprogram the host cellular chromatin landscape, thereby orchestrating the timely coordinated expression of genes involved in multiple signaling, immunoregulatory and metabolic processes.",2017 Mar 29,"['Poppe, Michael', 'Wittig, Sascha', 'Jurida, Liane', 'Bartkuhn, Marek', 'Wilhelm, Jochen', 'Müller, Helmut', 'Beuerlein, Knut', 'Karl, Nadja', 'Bhuju, Sabin', 'Ziebuhr, John', 'Schmitz, M. Lienhard', 'Kracht, Michael']",PLoS Pathog,,,True
7c4421b06ef3355f40059a452985306da5e5a66f,PMC,Analysis of the spleen proteome of chickens infected with reticuloendotheliosis virus,http://dx.doi.org/10.1007/s00705-016-3180-5,PMC5387025,28097424,CC BY,"Infection with reticuloendotheliosis virus (REV), a gammaretrovirus in the family Retroviridae, can result in immunosuppression and subsequent increased susceptibility to secondary infections. In the present study, we identified differentially expressed proteins in the spleens of chickens infected with the REV-A HLJ07I strain, using two-dimensional gel electrophoresis on samples from time points coinciding with different phases of the REV life cycle. Differentially expressed proteins were identified using one-dimensional liquid chromatography electrospray ionization tandem mass spectrometry (1D LC ESI MS/MS). Comparative analysis of multiple gels revealed that the majority of changes occurred at early stages of infection. In total, 60 protein spots representing 28 host proteins were detected as either quantitatively (false discovery rate [FDR] ≤0.05 and fold change ≥2) or qualitatively differentially expressed at least once during different sampling points. The differentially expressed proteins identified in this study included antioxidants, molecular chaperones, cellular metabolism, formation of the cytoskeleton, signal transduction, cell proliferation and cellar aging. The present findings provide a basis for further studies to elucidate the role of these proteins in REV-host interactions. This could lead to a better understanding of REV infection mechanisms that cause immune suppression.",2017 Jan 17,"['Xue, Mei', 'Zhao, Yan', 'Hu, Shunlei', 'Shi, Xingming', 'Cui, Hongyu', 'Wang, Yunfeng']",Arch Virol,,,True
d2d95788c3cd662cef7efad97646e0a9d2b3e47a,PMC,Progress and challenges in maternal health in western China: a Countdown to 2015 national case study,http://dx.doi.org/10.1016/S2214-109X(17)30100-6,PMC5387688,28341117,CC BY,"BACKGROUND: China is one of the few Countdown countries to have achieved Millennium Development Goal 5 (75% reduction in maternal mortality ratio between 1990 and 2015). We aimed to examine the health systems and contextual factors that might have contributed to the substantial decline in maternal mortality between 1997 and 2014. We chose to focus on western China because poverty, ethnic diversity, and geographical access represent particular challenges to ensuring universal access to maternal care in the region. METHODS: In this systematic assessment, we used data from national census reports, National Statistical Yearbooks, the National Maternal and Child Health Routine Reporting System, the China National Health Accounts report, and National Health Statistical Yearbooks to describe changes in policies, health financing, health workforce, health infrastructure, coverage of maternal care, and maternal mortality by region between 1997 and 2014. We used a multivariate linear regression model to examine which contextual and health systems factors contributed to the regional variation in maternal mortality ratio in the same period. Using data from a cross-sectional survey in 2011, we also examined equity in access to maternity care in 42 poor counties in western China. FINDINGS: Maternal mortality declined by 8·9% per year between 1997 and 2014 (geometric mean ratio for each year 0·91, 95% CI 0·91–0·92). After adjusting for GDP per capita, length of highways, female illiteracy, the number of licensed doctors per 1000 population, and the proportion of ethnic minorities, the maternal mortality ratio was 118% higher in the western region (2·18, 1·44–3·28) and 41% higher in the central region (1·41, 0·99–2·01) than in the eastern region. In the rural western region, the proportion of births in health facilities rose from 41·9% in 1997 to 98·4% in 2014. Underpinning such progress was the Government's strong commitment to long-term strategies to ensure access to delivery care in health facilities—eg, professionalisation of maternity care in large hospitals, effective referral systems for women medically or socially at high risk, and financial subsidies for antenatal and delivery care. However, in the poor western counties, substantial disparity by education level of the mother existed in access to health facility births (44% of illiterate women vs 100% of those with college or higher education), antenatal care (17% vs 69%) had at least four visits), and caesarean section (8% vs 44%). INTERPRETATION: Despite remarkable progress in maternal survival in China, substantial disparities remain, especially for the poor, less educated, and ethnic minority groups in remote areas in western China. Whether China's highly medicalised model of maternity care will be an answer for these populations is uncertain. A strategy modelled after China's immunisation programme, whereby care is provided close to the women's homes, might need to be explored, with township hospitals taking a more prominent role. FUNDING: Government of Canada, UNICEF, and the Bill & Melinda Gates Foundation.",2017 Mar 21,"['Gao, Yanqiu', 'Zhou, Hong', 'Singh, Neha S', 'Powell-Jackson, Timothy', 'Nash, Stephen', 'Yang, Min', 'Guo, Sufang', 'Fang, Hai', 'Alvarez, Melisa Martinez', 'Liu, Xiaoyun', 'Pan, Jay', 'Wang, Yan', 'Ronsmans, Carine']",Lancet Glob Health,,,False
6194d5f220da4fe7d477314cb4c1804c8c76a346,PMC,Progress and challenges in maternal health in western China: a Countdown to 2015 national case study,http://dx.doi.org/10.1016/S2214-109X(17)30100-6,PMC5387688,28341117,CC BY,"BACKGROUND: China is one of the few Countdown countries to have achieved Millennium Development Goal 5 (75% reduction in maternal mortality ratio between 1990 and 2015). We aimed to examine the health systems and contextual factors that might have contributed to the substantial decline in maternal mortality between 1997 and 2014. We chose to focus on western China because poverty, ethnic diversity, and geographical access represent particular challenges to ensuring universal access to maternal care in the region. METHODS: In this systematic assessment, we used data from national census reports, National Statistical Yearbooks, the National Maternal and Child Health Routine Reporting System, the China National Health Accounts report, and National Health Statistical Yearbooks to describe changes in policies, health financing, health workforce, health infrastructure, coverage of maternal care, and maternal mortality by region between 1997 and 2014. We used a multivariate linear regression model to examine which contextual and health systems factors contributed to the regional variation in maternal mortality ratio in the same period. Using data from a cross-sectional survey in 2011, we also examined equity in access to maternity care in 42 poor counties in western China. FINDINGS: Maternal mortality declined by 8·9% per year between 1997 and 2014 (geometric mean ratio for each year 0·91, 95% CI 0·91–0·92). After adjusting for GDP per capita, length of highways, female illiteracy, the number of licensed doctors per 1000 population, and the proportion of ethnic minorities, the maternal mortality ratio was 118% higher in the western region (2·18, 1·44–3·28) and 41% higher in the central region (1·41, 0·99–2·01) than in the eastern region. In the rural western region, the proportion of births in health facilities rose from 41·9% in 1997 to 98·4% in 2014. Underpinning such progress was the Government's strong commitment to long-term strategies to ensure access to delivery care in health facilities—eg, professionalisation of maternity care in large hospitals, effective referral systems for women medically or socially at high risk, and financial subsidies for antenatal and delivery care. However, in the poor western counties, substantial disparity by education level of the mother existed in access to health facility births (44% of illiterate women vs 100% of those with college or higher education), antenatal care (17% vs 69%) had at least four visits), and caesarean section (8% vs 44%). INTERPRETATION: Despite remarkable progress in maternal survival in China, substantial disparities remain, especially for the poor, less educated, and ethnic minority groups in remote areas in western China. Whether China's highly medicalised model of maternity care will be an answer for these populations is uncertain. A strategy modelled after China's immunisation programme, whereby care is provided close to the women's homes, might need to be explored, with township hospitals taking a more prominent role. FUNDING: Government of Canada, UNICEF, and the Bill & Melinda Gates Foundation.",2017 Mar 21,"['Gao, Yanqiu', 'Zhou, Hong', 'Singh, Neha S', 'Powell-Jackson, Timothy', 'Nash, Stephen', 'Yang, Min', 'Guo, Sufang', 'Fang, Hai', 'Alvarez, Melisa Martinez', 'Liu, Xiaoyun', 'Pan, Jay', 'Wang, Yan', 'Ronsmans, Carine']",Lancet Glob Health,,,False
d249845a31b0c4dac3b85502b7c8f9a3af5f0f31,PMC,Structure of the Ebola virus glycoprotein spike within the virion envelope at 11 Å resolution,http://dx.doi.org/10.1038/srep46374,PMC5387728,28397863,CC BY,"We present the structure of the surface Ebola virus (EBOV) trimeric glycoprotein (GP) spike at 11 Å resolution, in situ within the viral plasma membrane of purified virus particles. GP functions in cellular attachment, endosomal entry, and membrane fusion to initiate infection, and is a key therapeutic target. Nevertheless, only about half of the GP molecule has yet been solved to atomic resolution, excluding the mucin-like and transmembrane domains, and some of the glycans. Fitting of the atomic resolution X-ray data from expressed, truncated deletion constructs within our 11 Å structure of the entire molecule demonstrates the relationship between the GP1-GP2 domains, the mucin-like and transmembrane domains, and the bilaminar lipid envelope. We show that the mucin-like domain covers the glycan cap and partially occludes the receptor binding sites prior to proteolytic cleavage. Our structure is also consistent with key antibody neutralisation sites on GP being accessible prior to proteolysis. Based on the findings of us and others, GP-mediated binding may create an angle of 18 degrees between the planes of viral and endosomal membranes.",2017 Apr 11,"['Beniac, Daniel R.', 'Booth, Timothy F.']",Sci Rep,,,True
d2c09469b973994bcec7916dcef9a8b3de03fa96,PMC,Structure of the Ebola virus glycoprotein spike within the virion envelope at 11 Å resolution,http://dx.doi.org/10.1038/srep46374,PMC5387728,28397863,CC BY,"We present the structure of the surface Ebola virus (EBOV) trimeric glycoprotein (GP) spike at 11 Å resolution, in situ within the viral plasma membrane of purified virus particles. GP functions in cellular attachment, endosomal entry, and membrane fusion to initiate infection, and is a key therapeutic target. Nevertheless, only about half of the GP molecule has yet been solved to atomic resolution, excluding the mucin-like and transmembrane domains, and some of the glycans. Fitting of the atomic resolution X-ray data from expressed, truncated deletion constructs within our 11 Å structure of the entire molecule demonstrates the relationship between the GP1-GP2 domains, the mucin-like and transmembrane domains, and the bilaminar lipid envelope. We show that the mucin-like domain covers the glycan cap and partially occludes the receptor binding sites prior to proteolytic cleavage. Our structure is also consistent with key antibody neutralisation sites on GP being accessible prior to proteolysis. Based on the findings of us and others, GP-mediated binding may create an angle of 18 degrees between the planes of viral and endosomal membranes.",2017 Apr 11,"['Beniac, Daniel R.', 'Booth, Timothy F.']",Sci Rep,,,False
b0db6a5fa1ab9115d590c33a7934a6fbab65558e,PMC,GISAID: Global initiative on sharing all influenza data – from vision to reality,http://dx.doi.org/10.2807/1560-7917.ES.2017.22.13.30494,PMC5388101,28382917,CC BY,,2017 Mar 30,"['Shu, Yuelong', 'McCauley, John']",Euro Surveill,,,True
4c6ceb1e0f1dd785f1f6859da440c64e49824fb6,PMC,"Risk factors for MERS coronavirus infection in dromedary camels in Burkina Faso, Ethiopia, and Morocco, 2015",http://dx.doi.org/10.2807/1560-7917.ES.2017.22.13.30498,PMC5388105,28382915,CC BY,"Understanding Middle East respiratory syndrome coronavirus (MERS-CoV) transmission in dromedary camels is important, as they consitute a source of zoonotic infection to humans. To identify risk factors for MERS-CoV infection in camels bred in diverse conditions in Burkina Faso, Ethiopia and Morocco, blood samples and nasal swabs were sampled in February–March 2015. A relatively high MERS-CoV RNA rate was detected in Ethiopia (up to 15.7%; 95% confidence interval (CI): 8.2–28.0), followed by Burkina Faso (up to 12.2%; 95% CI: 7–20.4) and Morocco (up to 7.6%; 95% CI: 1.9–26.1). The RNA detection rate was higher in camels bred for milk or meat than in camels for transport (p = 0.01) as well as in younger camels (p = 0.06). High seropositivity rates (up to 100%; 95% CI: 100–100 and 99.4%; 95% CI: 95.4–99.9) were found in Morocco and Ethiopia, followed by Burkina Faso (up to 84.6%; 95% CI: 77.2–89.9). Seropositivity rates were higher in large/medium herds (≥51 camels) than small herds (p = 0.061), in camels raised for meat or milk than for transport (p = 0.01), and in nomadic or sedentary herds than in herds with a mix of these lifestyles (p < 0.005).",2017 Mar 30,"['Miguel, Eve', 'Chevalier, Véronique', 'Ayelet, Gelagay', 'Ben Bencheikh, Med Nadir', 'Boussini, Hiver', 'Chu, Daniel KW', 'El Berbri, Ikhlass', 'Fassi-Fihri, Ouaffa', 'Faye, Bernard', 'Fekadu, Getnet', 'Grosbois, Vladimir', 'Ng, Bryan CY', 'Perera, Ranawaka APM', 'So, TY', 'Traore, Amadou', 'Roger, François', 'Peiris, Malik']",Euro Surveill,,,True
16145009d7725e0b39d5522f56ac9781d258eeb8,PMC,20 years of communicating facts and figures,http://dx.doi.org/10.2807/1560-7917.ES.2016.21.48.30415,PMC5388113,27934580,CC BY,,2016 Dec 1,"Steffens, Ines",Euro Surveill,,,True
39e7645f7139f5677b413f08ef3bfecf1a1e9e66,PMC,"Severe acute respiratory infection caused by swine influenza virus in a child necessitating extracorporeal membrane oxygenation (ECMO), the Netherlands, October 2016",http://dx.doi.org/10.2807/1560-7917.ES.2016.21.48.30416,PMC5388114,27934581,CC BY,"In October 2016, a severe infection with swine influenza A(H1N1) virus of the Eurasian avian lineage occurred in a child with a previous history of eczema in the Netherlands, following contact to pigs. The patient’s condition deteriorated rapidly and required life support through extracorporeal membrane oxygenation. After start of oseltamivir treatment and removal of mucus plugs, the patient fully recovered. Monitoring of more than 80 close unprotected contacts revealed no secondary cases.",2016 Dec 1,"['Fraaij, Pieter L A', 'Wildschut, Enno D', 'Houmes, Robert J', 'Swaan, Corien M', 'Hoebe, Christian J', 'de Jonge, H C C', 'Tolsma, Paulien', 'de Kleer, Isme', 'Pas, Suzan D', 'Oude Munnink, Bas B', 'Phan, My V T', 'Bestebroer, Theo M', 'Roosenhoff, R Shanty', 'van Kampen, Jeroen J A', 'Cotten, Matthew', 'Beerens, Nancy', 'Fouchier, Ron A M', 'van den Kerkhof, Johannes H', 'Timen, Aura', 'Koopmans, Marion P']",Euro Surveill,,,True
17889315db35509927f4fd1fb1d656b800365377,PMC,"Risk of tuberculosis among air passengers estimated by interferon gamma release assay: survey of contact investigations, Japan, 2012 to 2015",http://dx.doi.org/10.2807/1560-7917.ES.2017.22.12.30492,PMC5388131,28367799,CC BY,"Although the World Health Organization recommends contact investigations around air travel-associated sputum smear-positive tuberculosis (TB) patients, evidence suggests that the information thus obtained may have overestimated the risk of TB infection because it involved some contacts born in countries with high TB burden who were likely to have been infected with TB in the past, or because tuberculin skin tests were used, which are less specific than the interferon gamma release assay (IGRA) particularly in areas where Bacillus Calmette-Guérin (BCG) vaccination coverage is high. We conducted a questionnaire survey on air travel-associated TB contact investigations in local health offices of Japan from 2012 to 2015, focusing on IGRA positivity. Among 651 air travel-associated TB contacts, average positivity was 3.8% (95% confidence interval (CI): 2.5–5.6) with a statistically significant increasing trend with older age (p < 0.0094). Positivity among 0–34 year-old contacts was 1.0% (95% CI: 0.12–3.5%), suggesting their risk of TB infection is as small as among Japanese young adults with low risk of TB infection (positivity: 0.85–0.90%). Limiting the contact investigation to fewer passengers (within two seats surrounding the index case, rather than two rows) seems reasonable in the case of aircraft with many seats per row.",2017 Mar 23,"['Ota, Masaki', 'Kato, Seiya']",Euro Surveill,,,True
0f64095c3f030c293ac087d505f3a3f64d110090,PMC,Habitat disturbance results in chronic stress and impaired health status in forest-dwelling paleotropical bats,http://dx.doi.org/10.1093/conphys/cox020,PMC5388297,28421138,CC BY,"Anthropogenic habitat disturbance is a major threat to biodiversity worldwide. Yet, before population declines are detectable, individuals may suffer from chronic stress and impaired immunity in disturbed habitats, making them more susceptible to pathogens and adverse weather conditions. Here, we tested in a paleotropical forest with ongoing logging and fragmentation, whether habitat disturbance influences the body mass and immunity of bats. We measured and compared body mass, chronic stress (indicated by neutrophil to lymphocyte ratios) and the number of circulating immune cells between several bat species with different roost types living in recovering areas, actively logged forests, and fragmented forests in Sabah, Malaysia. In a cave-roosting species, chronic stress levels were higher in individuals from fragmented habitats compared with conspecifics from actively logged areas. Foliage-roosting species showed a reduced body mass and decrease in total white blood cell counts in actively logged areas and fragmented forests compared with conspecifics living in recovering habitats. Our study highlights that habitat disturbance may have species-specific effects on chronic stress and immunity in bats that are potentially related to the roost type. We identified foliage-roosting species as particularly sensitive to forest habitat deterioration. These species may face a heightened extinction risk in the near future if anthropogenic habitat alterations continue.",2017 Apr 5,"['Seltmann, Anne', 'Czirják, Gábor Á.', 'Courtiol, Alexandre', 'Bernard, Henry', 'Struebig, Matthew J.', 'Voigt, Christian C.']",Conserv Physiol,,,True
f123d4b1f4b4e7a2f4fab9605258fbe053a2abd1,PMC,Interferon-inducible ribonuclease ISG20 inhibits hepatitis B virus replication through directly binding to the epsilon stem-loop structure of viral RNA,http://dx.doi.org/10.1371/journal.ppat.1006296,PMC5388505,28399146,CC BY,"Hepatitis B virus (HBV) replicates its DNA genome through reverse transcription of a viral RNA pregenome. We report herein that the interferon (IFN) stimulated exoribonuclease gene of 20 KD (ISG20) inhibits HBV replication through degradation of HBV RNA. ISG20 expression was observed at basal level and was highly upregulated upon IFN treatment in hepatocytes, and knock down of ISG20 resulted in elevation of HBV replication and attenuation of IFN-mediated antiviral effect. The sequence element conferring the susceptibility of HBV RNA to ISG20-mediated RNA degradation was mapped at the HBV RNA terminal redundant region containing epsilon (ε) stem-loop. Furthermore, ISG20-induced HBV RNA degradation relies on its ribonuclease activity, as the enzymatic inactive form ISG20(D94G) was unable to promote HBV RNA decay. Interestingly, ISG20(D94G) retained antiviral activity against HBV DNA replication by preventing pgRNA encapsidation, resulting from a consequence of ISG20-ε interaction. This interaction was further characterized by in vitro electrophoretic mobility shift assay (EMSA) and ISG20 was able to bind HBV ε directly in absence of any other cellular proteins, indicating a direct ε RNA binding capability of ISG20; however, cofactor(s) may be required for ISG20 to efficiently degrade ε. In addition, the lower stem portion of ε is the major ISG20 binding site, and the removal of 4 base pairs from the bottom portion of ε abrogated the sensitivity of HBV RNA to ISG20, suggesting that the specificity of ISG20-ε interaction relies on both RNA structure and sequence. Furthermore, the C-terminal Exonuclease III (ExoIII) domain of ISG20 was determined to be responsible for interacting with ε, as the deletion of ExoIII abolished in vitro ISG20-ε binding and intracellular HBV RNA degradation. Taken together, our study sheds light on the underlying mechanisms of IFN-mediated HBV inhibition and the antiviral mechanism of ISG20 in general.",2017 Apr 11,"['Liu, Yuanjie', 'Nie, Hui', 'Mao, Richeng', 'Mitra, Bidisha', 'Cai, Dawei', 'Yan, Ran', 'Guo, Ju-Tao', 'Block, Timothy M.', 'Mechti, Nadir', 'Guo, Haitao']",PLoS Pathog,,,True
0e7db64290a2be55897c1cedf4e15f2b5a86c06e,PMC,Interferon-inducible ribonuclease ISG20 inhibits hepatitis B virus replication through directly binding to the epsilon stem-loop structure of viral RNA,http://dx.doi.org/10.1371/journal.ppat.1006296,PMC5388505,28399146,CC BY,"Hepatitis B virus (HBV) replicates its DNA genome through reverse transcription of a viral RNA pregenome. We report herein that the interferon (IFN) stimulated exoribonuclease gene of 20 KD (ISG20) inhibits HBV replication through degradation of HBV RNA. ISG20 expression was observed at basal level and was highly upregulated upon IFN treatment in hepatocytes, and knock down of ISG20 resulted in elevation of HBV replication and attenuation of IFN-mediated antiviral effect. The sequence element conferring the susceptibility of HBV RNA to ISG20-mediated RNA degradation was mapped at the HBV RNA terminal redundant region containing epsilon (ε) stem-loop. Furthermore, ISG20-induced HBV RNA degradation relies on its ribonuclease activity, as the enzymatic inactive form ISG20(D94G) was unable to promote HBV RNA decay. Interestingly, ISG20(D94G) retained antiviral activity against HBV DNA replication by preventing pgRNA encapsidation, resulting from a consequence of ISG20-ε interaction. This interaction was further characterized by in vitro electrophoretic mobility shift assay (EMSA) and ISG20 was able to bind HBV ε directly in absence of any other cellular proteins, indicating a direct ε RNA binding capability of ISG20; however, cofactor(s) may be required for ISG20 to efficiently degrade ε. In addition, the lower stem portion of ε is the major ISG20 binding site, and the removal of 4 base pairs from the bottom portion of ε abrogated the sensitivity of HBV RNA to ISG20, suggesting that the specificity of ISG20-ε interaction relies on both RNA structure and sequence. Furthermore, the C-terminal Exonuclease III (ExoIII) domain of ISG20 was determined to be responsible for interacting with ε, as the deletion of ExoIII abolished in vitro ISG20-ε binding and intracellular HBV RNA degradation. Taken together, our study sheds light on the underlying mechanisms of IFN-mediated HBV inhibition and the antiviral mechanism of ISG20 in general.",2017 Apr 11,"['Liu, Yuanjie', 'Nie, Hui', 'Mao, Richeng', 'Mitra, Bidisha', 'Cai, Dawei', 'Yan, Ran', 'Guo, Ju-Tao', 'Block, Timothy M.', 'Mechti, Nadir', 'Guo, Haitao']",PLoS Pathog,,,False
66f3b61dee5fb0898bad0667c35c210bdd020b9f,PMC,Media effects on suicide methods: A case study on Hong Kong 1998-2005,http://dx.doi.org/10.1371/journal.pone.0175580,PMC5389840,28403231,CC BY,"BACKGROUND: Previous studies have suggested that mass media’s reports of new suicide methods will increase suicides using the same method. The same pattern seems not to apply to a conventional suicide method, unless it was used by a celebrity. OBJECTIVE: 1) to examine media effects on both new and non-new suicide methods during 1998 and 2005 in Hong Kong (HK), when a new method by burning charcoal (CB suicide) was spreading in the region. 2) to examine how CB competed with non-CB methods in terms of media coverage and “recruiting” suicidal persons in the socio-economic context. METHODS: A self- and mutual- exciting process model was fitted to the data, adjusting for divorce rate, unemployment rate, and property price index. Breaking the whole period into onset, peak, and post-peak stages, the model was fitted again to examine the differences. RESULTS: Comparable copycat effects were found on both CB and non-CB suicide news. The only cross-method media effects were found in the onset stage when non-CB suicide news showed suppressing effect on CB suicides. CB suicides reported a significant self-excitation effect. A higher divorce rate and lower property price index were associated with significantly more suicides incidences and more suicide news. CONCLUSIONS: The emerging of CB suicide method did not substitute media coverage of non-CB suicide in HK. Media effects in this case were not limited to new suicide method or celebrity suicide. The effects were further fueled by adverse socio-economic conditions.",2017 Apr 12,"['Cheng, Qijin', 'Chen, Feng', 'Yip, Paul S. F.']",PLoS One,,,True
4fa344b02899cb75cb81db82d2cee5f624343c54,PMC,Glucose-regulated protein 78 demonstrates antiviral effects but is more suitable for hepatocellular carcinoma prevention in hepatitis B,http://dx.doi.org/10.1186/s12985-017-0747-z,PMC5390389,28407787,CC BY,"BACKGROUND: Hepatitis B virus (HBV) is the leading cause of liver cirrhosis and hepatocellular carcinoma in Asia and Africa. Existing antivirals cannot cure HBV or eliminate risk of hepatocellular carcinoma. Glucose-regulated protein 78 (GRP78) can inhibit HBV replication, but promote virion secretion and hepatocellular cancer cell invasion. For these reasons, the overall effect of GRP78 on HBV production and whether to utilize the HBV replication-inhibitory effect of GRP78 up-regulation or the hepatocellular cancer cell invasion-inhibitory effect of its down-regulation were further investigated in order to improve the efficacy of current antiviral therapy. METHODS: GRP78 regulations in HepG2.2.15 cells were conducted by transfections of expressing vector and small interfering RNA, respectively. The changes in HBV replication, hepatitis B e antigen (HBeAg) synthesis and hepatoma cell motility were monitored. RESULTS: GRP78 overall decreased HBV production due to its HBV replication-inhibitory effect time-dependently overwhelming virion secretion-promoting effect in HepG2.2.15 cells. Unlike the parental cells (HepG2), HepG2.2.15 cells demonstrated decreased expressions of the major genes in the interferon-β1-dependent pathway. Moreover, the expressions of these genes were not affected by GRP78 regulations. However, GRP78 was found to inhibit HBeAg secretion and to increase the retro-transportation of capsid assembly-interfering HBeAg precursor from the endoplasmic reticulum into the cytosol where new viral nucleocapsids formed. Furthermore, GRP78 overexpression promoted wound healing process (the motility) of HepG2.2.15 cells. In contrast, GRP78 knockdown enhanced HBV replication and HBeAg secretion, but they were abolished by entecavir and furin inhibitor, respectively. CONCLUSIONS: GRP78 mainly demonstrates anti-HBV effects, reducing HBV production and HBeAg secretion. With due regard to the hepatocellular cancer invasion risk of the overexpression and the rectifiability of the unpleasant effects of the knockdown, GRP78 down-regulation may be more suitable to serve as an additive strategy to cover the hepatocellular cancer prevention shortage of current antiviral therapy in the future.",2017 Apr 13,"['Zheng, Nai Q.', 'Zheng, Zi H.', 'Xu, Hai X.', 'Huang, Ming X.', 'Peng, Xiao M.']",Virol J,,,True
2911b1cc77f7c2bf1f8743673d3d2df7d7993aee,PMC,The Functional Roles of the Cis-acting Elements in Bamboo mosaic virus RNA Genome,http://dx.doi.org/10.3389/fmicb.2017.00645,PMC5390519,28450857,CC BY,"Bamboo mosaic virus (BaMV), which belongs to the genus Potexvirus in the family Alphaflexiviridae, has a single-stranded positive-sense RNA genome that is approximately 6400 nucleotides (nts) in length. Positive-sense RNA viruses can use genomic RNA as a template for translation and replication after entering a suitable host cell. Furthermore, such viral RNA is recognized by capsid protein for packaging and by viral movement protein(s) or the movement protein complex for cell-to-cell and systemic movement. Hence, viral RNA must contain signals for different functions to complete the viral infection cycle. In this review, we examine various cis-acting elements in the genome of BaMV. The highly structured 3′ untranslated region (UTR) of the BaMV genomic RNA plays multiple roles in the BaMV infection cycle, including targeting chloroplasts for RNA replication, providing an initiation site for the synthesis of minus-strand RNA, signaling for polyadenylation, and directing viral long-distance movement. The nt at the extreme 3′ end and the structure of the 3′-terminus of minus-strand RNA are involved in the initiation of plus-strand genomic RNA synthesis. Both these regions have been mapped and reported to interact with the viral-encoded RNA-dependent RNA polymerase. Moreover, the sequences upstream of open reading frames (ORFs) 2, 3, and 5 are involved in regulating subgenomic RNA synthesis. The cis-acting elements that were identified in BaMV RNA are discussed and compared with those of other potexviruses.",2017 Apr 13,"['Chen, I-Hsuan', 'Huang, Ying-Wen', 'Tsai, Ching-Hsiu']",Front Microbiol,,,True
fe60210f629f9953405917869332d549f39e5a1b,PMC,The Structure of a Rigorously Conserved RNA Element within the SARS Virus Genome,http://dx.doi.org/10.1371/journal.pbio.0030005,PMC539059,15630477,CC BY,"We have solved the three-dimensional crystal structure of the stem-loop II motif (s2m) RNA element of the SARS virus genome to 2.7-Å resolution. SARS and related coronaviruses and astroviruses all possess a motif at the 3′ end of their RNA genomes, called the s2m, whose pathogenic importance is inferred from its rigorous sequence conservation in an otherwise rapidly mutable RNA genome. We find that this extreme conservation is clearly explained by the requirement to form a highly structured RNA whose unique tertiary structure includes a sharp 90° kink of the helix axis and several novel longer-range tertiary interactions. The tertiary base interactions create a tunnel that runs perpendicular to the main helical axis whose interior is negatively charged and binds two magnesium ions. These unusual features likely form interaction surfaces with conserved host cell components or other reactive sites required for virus function. Based on its conservation in viral pathogen genomes and its absence in the human genome, we suggest that these unusual structural features in the s2m RNA element are attractive targets for the design of anti-viral therapeutic agents. Structural genomics has sought to deduce protein function based on three-dimensional homology. Here we have extended this approach to RNA by proposing potential functions for a rigorously conserved set of RNA tertiary structural interactions that occur within the SARS RNA genome itself. Based on tertiary structural comparisons, we propose the s2m RNA binds one or more proteins possessing an oligomer-binding-like fold, and we suggest a possible mechanism for SARS viral RNA hijacking of host protein synthesis, both based upon observed s2m RNA macromolecular mimicry of a relevant ribosomal RNA fold.",2005 Jan 28,"['Robertson, Michael P', 'Igel, Haller', 'Baertsch, Robert', 'Haussler, David', 'Ares, Manuel', 'Scott, William G']",PLoS Biol,,,True
d02169bfa790e68565fa472a3e06c7c3ac1977e0,PMC,Structure of a Conserved RNA Element in the SARS Virus Genome Determined,http://dx.doi.org/10.1371/journal.pbio.0030029,PMC539063,,CC BY,,2005 Jan 28,,PLoS Biol,,,False
d18636f47e3c7dd93da309d556ba464d964fd24f,PMC,The Long Noncoding RNA NEAT1 Exerts Antihantaviral Effects by Acting as Positive Feedback for RIG-I Signaling,http://dx.doi.org/10.1128/JVI.02250-16,PMC5391460,28202761,CC BY,"Hantavirus infection, which causes zoonotic diseases with a high mortality rate in humans, has long been a global public health concern. Over the past decades, accumulating evidence suggests that long noncoding RNAs (lncRNAs) play key regulatory roles in innate immunity. However, the involvement of host lncRNAs in hantaviral control remains uncharacterized. In this study, we identified the lncRNA NEAT1 as a vital antiviral modulator. NEAT1 was dramatically upregulated after Hantaan virus (HTNV) infection, whereas its downregulation in vitro or in vivo delayed host innate immune responses and aggravated HTNV replication. Ectopic expression of NEAT1 enhanced beta interferon (IFN-β) production and suppressed HTNV infection. Further investigation suggested that NEAT1 served as positive feedback for RIG-I signaling. HTNV infection activated NEAT1 transcription through the RIG-I–IRF7 pathway, whereas NEAT1 removed the transcriptional inhibitory effects of the splicing factor proline- and glutamine-rich protein (SFPQ) by relocating SFPQ to paraspeckles, thus promoting the expression of RIG-I and DDX60. RIG-I and DDX60 had synergic effects on IFN production. Taken together, our findings demonstrate that NEAT1 modulates the innate immune response against HTNV infection, providing another layer of information about the role of lncRNAs in controlling viral infections. IMPORTANCE Hantaviruses have attracted worldwide attention as archetypal emerging pathogens. Recently, increasing evidence has highlighted long noncoding RNAs (lncRNAs) as key regulators of innate immunity; however, their roles in hantavirus infection remain unknown. In the present work, a new unexplored function of lncRNA NEAT1 in controlling HTNV replication was found. NEAT1 promoted interferon (IFN) responses by acting as positive feedback for RIG-I signaling. This lncRNA was induced by HTNV through the RIG-I–IRF7 pathway in a time- and dose-dependent manner and promoted HTNV-induced IFN production by facilitating RIG-I and DDX60 expression. Intriguingly, NEAT1 relocated SFPQ and formed paraspeckles after HTNV infection, which might reverse inhibitive effects of SFPQ on the transcription of RIG-I and DDX60. To the best of our knowledge, this is the first study to address the regulatory role of the lncRNA NEAT1 in host innate immunity after HTNV infection. In summary, our findings provide additional insights regarding the role of lncRNAs in controlling viral infections.",2017 Apr 13,"['Ma, Hongwei', 'Han, Peijun', 'Ye, Wei', 'Chen, Hesong', 'Zheng, Xuyang', 'Cheng, Linfeng', 'Zhang, Liang', 'Yu, Lan', ""Wu, Xing'an"", 'Xu, Zhikai', 'Lei, Yingfeng', 'Zhang, Fanglin']",J Virol,,,True
5d62acbb74aea7559783bcf556ce7352b55ca03a,PMC,Cross-sectional survey of selected enteric viruses in Polish turkey flocks between 2008 and 2011,http://dx.doi.org/10.1186/s12917-017-1013-8,PMC5391614,28410608,CC BY,"BACKGROUND: Enteric diseases are an important health problem for the intensive poultry industry, resulting in considerable economic losses. Apart from such microbiological agents associated with enteritis as bacteria and parasites, a lot of research has been recently conducted on viral origin of enteric diseases. However, enteric viruses have been identified in intestinal tract of not only diseased but also healthy poultry, so their role in enteritis is still unclear. The present study aimed at determination of the prevalence of four enteric viruses, namely astrovirus, coronavirus, parvovirus and rotavirus in meat-type turkey flocks in Poland as well as at statistical evaluation of the occurrence of the studied viruses and their relationships with the health status and the age of birds. Two hundred and seven flocks of birds aged 1-20 weeks originating from different regions of the country were investigated between 2008 and 2011. Clinical samples (10 individual faecal swabs/flock) were duly processed and examined using molecular methods targeting the conservative regions of viral genomes: RNA-dependent RNA polymerase gene of astrovirus, non-structural 1 gene of parvovirus, non-structural protein 4 gene of rotavirus, and 5′ untranslated region fragment of turkey coronavirus. Different statistical methods (i.e. the independence chi-square test, the correspondence analysis and the logistic regression model) were used to establish any relationships between the analyzed data. RESULTS: Overall, 137 (66.2%, 95% CI: 59.3-72.6) of the 207 turkey flocks sampled were infected with one or more enteric viruses. Among the 137 flocks, 74 (54%, 95% CI: 45.3-62.6) were positive for one virus, whereas 54 (39.4%, 9 5% CI: 31.2-48.1) and 9 (6.6%, 95% CI: 3.1-12.1) were co-infected with two or three different enteric viruses, respectively. No flock was simultaneously infected with all four viruses studied. The prevalence of astrovirus infection was 44.9% (95% CI: 38.0-52.0), parvovirus 27.5% (95% CI: 21.6-34.2), rotavirus 18.8% (95% CI: 13.8-24.8), and coronavirus 9.7% (95% CI: 6.0-14.5). Young turkeys aged 1-4 weeks old had the highest (82.1%, 95% CI:71.7-89.8) prevalence of viral infection. Applied statistical methods have indicated the dependence of rotavirus infection as well as the co-infection with multiple viruses and the health status of turkeys. Furthermore, our results statistically confirm that especially young birds are susceptible to infection with rotavirus and astrovirus. CONCLUSIONS: The study demonstrated the presence of astrovirus, coronavirus, parvovirus and rotavirus infections in Polish turkey farms. These viruses were detected in both healthy and diseased birds. However, the presented results provide valuable feedback which could help to evaluate the role of some enteric viruses in the etiology of enteritis in turkey.",2017 Apr 14,"['Domańska-Blicharz, K.', 'Bocian, Ł.', 'Lisowska, A.', 'Jacukowicz, A.', 'Pikuła, A.', 'Minta, Z.']",BMC Vet Res,,,True
073cdd46009615f49f9c9c074e55ecebe8305d32,PMC,Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains,http://dx.doi.org/10.1038/ncomms15092,PMC5394239,28393837,CC BY,"The envelope spike (S) proteins of MERS-CoV and SARS-CoV determine the virus host tropism and entry into host cells, and constitute a promising target for the development of prophylactics and therapeutics. Here, we present high-resolution structures of the trimeric MERS-CoV and SARS-CoV S proteins in its pre-fusion conformation by single particle cryo-electron microscopy. The overall structures resemble that from other coronaviruses including HKU1, MHV and NL63 reported recently, with the exception of the receptor binding domain (RBD). We captured two states of the RBD with receptor binding region either buried (lying state) or exposed (standing state), demonstrating an inherently flexible RBD readily recognized by the receptor. Further sequence conservation analysis of six human-infecting coronaviruses revealed that the fusion peptide, HR1 region and the central helix are potential targets for eliciting broadly neutralizing antibodies.",2017 Apr 10,"['Yuan, Yuan', 'Cao, Duanfang', 'Zhang, Yanfang', 'Ma, Jun', 'Qi, Jianxun', 'Wang, Qihui', 'Lu, Guangwen', 'Wu, Ying', 'Yan, Jinghua', 'Shi, Yi', 'Zhang, Xinzheng', 'Gao, George F.']",Nat Commun,,,True
bda2ade25b4dbcb7b20ef7114e195f0e3285a781,PMC,Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains,http://dx.doi.org/10.1038/ncomms15092,PMC5394239,28393837,CC BY,"The envelope spike (S) proteins of MERS-CoV and SARS-CoV determine the virus host tropism and entry into host cells, and constitute a promising target for the development of prophylactics and therapeutics. Here, we present high-resolution structures of the trimeric MERS-CoV and SARS-CoV S proteins in its pre-fusion conformation by single particle cryo-electron microscopy. The overall structures resemble that from other coronaviruses including HKU1, MHV and NL63 reported recently, with the exception of the receptor binding domain (RBD). We captured two states of the RBD with receptor binding region either buried (lying state) or exposed (standing state), demonstrating an inherently flexible RBD readily recognized by the receptor. Further sequence conservation analysis of six human-infecting coronaviruses revealed that the fusion peptide, HR1 region and the central helix are potential targets for eliciting broadly neutralizing antibodies.",2017 Apr 10,"['Yuan, Yuan', 'Cao, Duanfang', 'Zhang, Yanfang', 'Ma, Jun', 'Qi, Jianxun', 'Wang, Qihui', 'Lu, Guangwen', 'Wu, Ying', 'Yan, Jinghua', 'Shi, Yi', 'Zhang, Xinzheng', 'Gao, George F.']",Nat Commun,,,False
73c4a4a2b71de0eed3628178ec3b56b84887527d,PMC,Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains,http://dx.doi.org/10.1038/ncomms15092,PMC5394239,28393837,CC BY,"The envelope spike (S) proteins of MERS-CoV and SARS-CoV determine the virus host tropism and entry into host cells, and constitute a promising target for the development of prophylactics and therapeutics. Here, we present high-resolution structures of the trimeric MERS-CoV and SARS-CoV S proteins in its pre-fusion conformation by single particle cryo-electron microscopy. The overall structures resemble that from other coronaviruses including HKU1, MHV and NL63 reported recently, with the exception of the receptor binding domain (RBD). We captured two states of the RBD with receptor binding region either buried (lying state) or exposed (standing state), demonstrating an inherently flexible RBD readily recognized by the receptor. Further sequence conservation analysis of six human-infecting coronaviruses revealed that the fusion peptide, HR1 region and the central helix are potential targets for eliciting broadly neutralizing antibodies.",2017 Apr 10,"['Yuan, Yuan', 'Cao, Duanfang', 'Zhang, Yanfang', 'Ma, Jun', 'Qi, Jianxun', 'Wang, Qihui', 'Lu, Guangwen', 'Wu, Ying', 'Yan, Jinghua', 'Shi, Yi', 'Zhang, Xinzheng', 'Gao, George F.']",Nat Commun,,,False
720d81cbf900cfce68db61398f8c41f92f798314,PMC,Inflammatory Responses Regulating Alveolar Ion Transport during Pulmonary Infections,http://dx.doi.org/10.3389/fimmu.2017.00446,PMC5394420,28458673,CC BY,"The respiratory epithelium is lined by a tightly balanced fluid layer that allows normal O(2) and CO(2) exchange and maintains surface tension and host defense. To maintain alveolar fluid homeostasis, both the integrity of the alveolar–capillary barrier and the expression of epithelial ion channels and pumps are necessary to establish a vectorial ion gradient. However, during pulmonary infection, auto- and/or paracrine-acting mediators induce pathophysiological changes of the alveolar–capillary barrier, altered expression of epithelial Na,K-ATPase and of epithelial ion channels including epithelial sodium channel and cystic fibrosis membrane conductance regulator, leading to the accumulation of edema and impaired alveolar fluid clearance. These mediators include classical pro-inflammatory cytokines such as TGF-β, TNF-α, interferons, or IL-1β that are released upon bacterial challenge with Streptococcus pneumoniae, Klebsiella pneumoniae, or Mycoplasma pneumoniae as well as in viral infection with influenza A virus, pathogenic coronaviruses, or respiratory syncytial virus. Moreover, the pro-apoptotic mediator TNF-related apoptosis-inducing ligand, extracellular nucleotides, or reactive oxygen species impair epithelial ion channel expression and function. Interestingly, during bacterial infection, alterations of ion transport function may serve as an additional feedback loop on the respiratory inflammatory profile, further aggravating disease progression. These changes lead to edema formation and impair edema clearance which results in suboptimal gas exchange causing hypoxemia and hypercapnia. Recent preclinical studies suggest that modulation of the alveolar–capillary fluid homeostasis could represent novel therapeutic approaches to improve outcomes in infection-induced lung injury.",2017 Apr 18,"['Peteranderl, Christin', 'Sznajder, Jacob I.', 'Herold, Susanne', 'Lecuona, Emilia']",Front Immunol,,,True
feb7c5090a73fadeb2bde113221095746da8f12b,PMC,Offering patients more: how the West Africa Ebola outbreak can shape innovation in therapeutic research for emerging and epidemic infections,http://dx.doi.org/10.1098/rstb.2016.0294,PMC5394634,28396467,CC BY,"Although, after an epidemic of over 28 000 cases, there are still no licensed treatments for Ebola virus disease (EVD), significant progress was made during the West Africa outbreak. The pace of pre-clinical development was exceptional and a number of therapeutic clinical trials were conducted in the face of considerable challenges. Given the on-going risk of emerging infectious disease outbreaks in an era of unprecedented population density, international travel and human impact on the environment it is pertinent to focus on improving the research and development landscape for treatments of emerging and epidemic-prone infections. This is especially the case since there are no licensed therapeutics for some of the diseases considered by the World Health Organization as most likely to cause severe outbreaks—including Middle East respiratory syndrome coronavirus, Marburg virus, Crimean Congo haemorrhagic fever and Nipah virus. EVD, therefore, provides a timely exemplar to discuss the barriers, enablers and incentives needed to find effective treatments in advance of health emergencies caused by emerging infectious diseases. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.",2017 May 26,"['Rojek, Amanda M.', 'Horby, Peter W.']",Philos Trans R Soc Lond B Biol Sci,,,True
2f464f69ee34fff67b35b41170660a4e3dac0654,PMC,A review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines?,http://dx.doi.org/10.1098/rstb.2016.0295,PMC5394635,28396468,CC BY,"Sporadic outbreaks of Ebola virus infection have been documented since the mid-Seventies and viral exposure can lead to lethal haemorrhagic fever with case fatalities as high as 90%. There is now a comprehensive body of data from both ongoing and completed clinical trials assessing various vaccine strategies, which were rapidly advanced through clinical trials in response to the 2013–2016 Ebola virus disease (EVD) public health emergency. Careful consideration of immunogenicity post vaccination is essential but has been somewhat stifled because of the wide array of immunological assays and outputs that have been used in the numerous clinical trials. We discuss here the different aspects of the immune assays currently used in the Phase I clinical trials for Ebola virus vaccines, and draw comparisons across the immune outputs where possible; various trials have examined both cellular and humoral immunity in European and African cohorts. Assessment of the safety data, the immunological outputs and the ease of field deployment for the various vaccine modalities will help both the scientific community and policy-makers prioritize and potentially license vaccine candidates. If this can be achieved, the next outbreak of Ebola virus, or other emerging pathogen, can be more readily contained and will not have such widespread and devastating consequences. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.",2017 May 26,"['Lambe, Teresa', 'Bowyer, Georgina', 'Ewer, Katie J']",Philos Trans R Soc Lond B Biol Sci,,,True
f45c3a707e3c465ca99703e6ea202702841a5b97,PMC,Key data for outbreak evaluation: building on the Ebola experience,http://dx.doi.org/10.1098/rstb.2016.0371,PMC5394647,28396480,CC BY,"Following the detection of an infectious disease outbreak, rapid epidemiological assessment is critical for guiding an effective public health response. To understand the transmission dynamics and potential impact of an outbreak, several types of data are necessary. Here we build on experience gained in the West African Ebola epidemic and prior emerging infectious disease outbreaks to set out a checklist of data needed to: (1) quantify severity and transmissibility; (2) characterize heterogeneities in transmission and their determinants; and (3) assess the effectiveness of different interventions. We differentiate data needs into individual-level data (e.g. a detailed list of reported cases), exposure data (e.g. identifying where/how cases may have been infected) and population-level data (e.g. size/demographics of the population(s) affected and when/where interventions were implemented). A remarkable amount of individual-level and exposure data was collected during the West African Ebola epidemic, which allowed the assessment of (1) and (2). However, gaps in population-level data (particularly around which interventions were applied when and where) posed challenges to the assessment of (3). Here we highlight recurrent data issues, give practical suggestions for addressing these issues and discuss priorities for improvements in data collection in future outbreaks. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.",2017 May 26,"['Cori, Anne', 'Donnelly, Christl A.', 'Dorigatti, Ilaria', 'Ferguson, Neil M.', 'Fraser, Christophe', 'Garske, Tini', 'Jombart, Thibaut', 'Nedjati-Gilani, Gemma', 'Nouvellet, Pierre', 'Riley, Steven', 'Van Kerkhove, Maria D.', 'Mills, Harriet L.', 'Blake, Isobel M.']",Philos Trans R Soc Lond B Biol Sci,,,True
7d786df32810bc6ce9c8a4aecbd5300477407dd6,PMC,Key data for outbreak evaluation: building on the Ebola experience,http://dx.doi.org/10.1098/rstb.2016.0371,PMC5394647,28396480,CC BY,"Following the detection of an infectious disease outbreak, rapid epidemiological assessment is critical for guiding an effective public health response. To understand the transmission dynamics and potential impact of an outbreak, several types of data are necessary. Here we build on experience gained in the West African Ebola epidemic and prior emerging infectious disease outbreaks to set out a checklist of data needed to: (1) quantify severity and transmissibility; (2) characterize heterogeneities in transmission and their determinants; and (3) assess the effectiveness of different interventions. We differentiate data needs into individual-level data (e.g. a detailed list of reported cases), exposure data (e.g. identifying where/how cases may have been infected) and population-level data (e.g. size/demographics of the population(s) affected and when/where interventions were implemented). A remarkable amount of individual-level and exposure data was collected during the West African Ebola epidemic, which allowed the assessment of (1) and (2). However, gaps in population-level data (particularly around which interventions were applied when and where) posed challenges to the assessment of (3). Here we highlight recurrent data issues, give practical suggestions for addressing these issues and discuss priorities for improvements in data collection in future outbreaks. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.",2017 May 26,"['Cori, Anne', 'Donnelly, Christl A.', 'Dorigatti, Ilaria', 'Ferguson, Neil M.', 'Fraser, Christophe', 'Garske, Tini', 'Jombart, Thibaut', 'Nedjati-Gilani, Gemma', 'Nouvellet, Pierre', 'Riley, Steven', 'Van Kerkhove, Maria D.', 'Mills, Harriet L.', 'Blake, Isobel M.']",Philos Trans R Soc Lond B Biol Sci,,,False
678acf32701e180748dd32a5d26e4b0c4900cdab,PMC,Key data for outbreak evaluation: building on the Ebola experience,http://dx.doi.org/10.1098/rstb.2016.0371,PMC5394647,28396480,CC BY,"Following the detection of an infectious disease outbreak, rapid epidemiological assessment is critical for guiding an effective public health response. To understand the transmission dynamics and potential impact of an outbreak, several types of data are necessary. Here we build on experience gained in the West African Ebola epidemic and prior emerging infectious disease outbreaks to set out a checklist of data needed to: (1) quantify severity and transmissibility; (2) characterize heterogeneities in transmission and their determinants; and (3) assess the effectiveness of different interventions. We differentiate data needs into individual-level data (e.g. a detailed list of reported cases), exposure data (e.g. identifying where/how cases may have been infected) and population-level data (e.g. size/demographics of the population(s) affected and when/where interventions were implemented). A remarkable amount of individual-level and exposure data was collected during the West African Ebola epidemic, which allowed the assessment of (1) and (2). However, gaps in population-level data (particularly around which interventions were applied when and where) posed challenges to the assessment of (3). Here we highlight recurrent data issues, give practical suggestions for addressing these issues and discuss priorities for improvements in data collection in future outbreaks. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.",2017 May 26,"['Cori, Anne', 'Donnelly, Christl A.', 'Dorigatti, Ilaria', 'Ferguson, Neil M.', 'Fraser, Christophe', 'Garske, Tini', 'Jombart, Thibaut', 'Nedjati-Gilani, Gemma', 'Nouvellet, Pierre', 'Riley, Steven', 'Van Kerkhove, Maria D.', 'Mills, Harriet L.', 'Blake, Isobel M.']",Philos Trans R Soc Lond B Biol Sci,,,False
435b58b1b6b499274125be7c1b8d903fe6368959,PMC,An approach to and web-based tool for infectious disease outbreak intervention analysis,http://dx.doi.org/10.1038/srep46076,PMC5394686,28417983,CC BY,"Infectious diseases are a leading cause of death globally. Decisions surrounding how to control an infectious disease outbreak currently rely on a subjective process involving surveillance and expert opinion. However, there are many situations where neither may be available. Modeling can fill gaps in the decision making process by using available data to provide quantitative estimates of outbreak trajectories. Effective reduction of the spread of infectious diseases can be achieved through collaboration between the modeling community and public health policy community. However, such collaboration is rare, resulting in a lack of models that meet the needs of the public health community. Here we show a Susceptible-Infectious-Recovered (SIR) model modified to include control measures that allows parameter ranges, rather than parameter point estimates, and includes a web user interface for broad adoption. We apply the model to three diseases, measles, norovirus and influenza, to show the feasibility of its use and describe a research agenda to further promote interactions between decision makers and the modeling community.",2017 Apr 18,"['Daughton, Ashlynn R.', 'Generous, Nicholas', 'Priedhorsky, Reid', 'Deshpande, Alina']",Sci Rep,,,True
b515cc5df8df49a37037106bfe3d94a2370e30bd,PMC,"Quality Evaluation of Juniperus rigida Sieb. et Zucc. Based on Phenolic Profiles, Bioactivity, and HPLC Fingerprint Combined with Chemometrics",http://dx.doi.org/10.3389/fphar.2017.00198,PMC5395569,28469573,CC BY,"Juniperus rigida (J. rigida) which is endemic to East Asia, has traditionally been used as an ethnomedicinal plant in China. This study was undertaken to evaluate the quality of J. rigida samples derived from 11 primary regions in China. Ten phenolic compounds were simultaneously quantified using reversed-phase high-performance liquid chromatography (RP-HPLC), and chlorogenic acid, catechin, podophyllotoxin, and amentoflavone were found to be the main compounds in J. rigida needles, with the highest contents detected for catechin and podophyllotoxin. J. rigida from Jilin (S9, S10) and Liaoning (S11) exhibited the highest contents of phenolic profiles (total phenolics, total flavonoids and 10 phenolic compounds) and the strongest antioxidant and antibacterial activities, followed by Shaanxi (S2, S3). A similarity analysis (SA) demonstrated substantial similarities in fingerprint chromatograms, from which 14 common peaks were selected. The similarity values varied from 0.85 to 0.98. Chemometrics techniques, including hierarchical cluster analysis (HCA), principal component analysis (PCA), and discriminant analysis (DA), were further applied to facilitate accurate classification and quantification of the J. rigida samples derived from the 11 regions. The results supported HPLC data showing that all J. rigida samples exhibit considerable variations in phenolic profiles, and the samples were further clustered into three major groups coincident with their geographical regions of origin. In addition, two discriminant functions with a 100% discrimination ratio were constructed to further distinguish and classify samples with unknown membership on the basis of eigenvalues to allow optimal discrimination among the groups. Our comprehensive findings on matching phenolic profiles and bioactivities along with data from fingerprint chromatograms with chemometrics provide an effective tool for screening and quality evaluation of J. rigida and related medicinal preparations.",2017 Apr 19,"['Liu, Zehua', 'Wang, Dongmei', 'Li, Dengwu', 'Zhang, Shuai']",Front Pharmacol,,,True
64f8cf1eb3fcbf713912d805032e3c95d4dda259,PMC,Immunological properties of gold nanoparticles,http://dx.doi.org/10.1039/c6sc03631g,PMC5396510,28451297,CC BY,"In the past decade, gold nanoparticles have attracted strong interest from the nanobiotechnological community owing to the significant progress made in robust and easy-to-make synthesis technologies, in surface functionalization, and in promising biomedical applications. These include bioimaging, gene diagnostics, analytical sensing, photothermal treatment of tumors, and targeted delivery of various biomolecular and chemical cargos. For the last-named application, gold nanoparticles should be properly fabricated to deliver the cargo into the targeted cells through effective endocytosis. In this review, we discuss recent progress in understanding the selective penetration of gold nanoparticles into immune cells. The interaction of gold nanoparticles with immune cell receptors is discussed. As distinct from other published reviews, we present a summary of the immunological properties of gold nanoparticles. This review also summarizes what is known about the application of gold nanoparticles as an antigen carrier and adjuvant in immunization for the preparation of antibodies in vivo. For each of the above topics, the basic principles, recent advances, and current challenges are discussed. Thus, this review presents a detailed analysis of data on interaction of gold nanoparticles with immune cells. Emphasis is placed on the systematization of data over production of antibodies by using gold nanoparticles and adjuvant properties of gold nanoparticles. Specifically, we start our discussion with current data on interaction of various gold nanoparticles with immune cells. The next section describes existing technologies to improve production of antibodies in vivo by using gold nanoparticles conjugated with specific ligands. Finally, we describe what is known about adjuvant properties of bare gold or functionalized nanoparticles. In the Conclusion section, we present a short summary of reported data and some challenges and perspectives.",2017 Mar 1,"['Dykman, Lev A.', 'Khlebtsov, Nikolai G.']",Chem Sci,,,True
fa5d4e0d5a2afc924b07e8835aa0ac3cf0646089,PMC,Avian Interferon-Inducible Transmembrane Protein Family Effectively Restricts Avian Tembusu Virus Infection,http://dx.doi.org/10.3389/fmicb.2017.00672,PMC5397487,28473814,CC BY,"Avian Tembusu virus (ATMUV) is a highly pathogenic flavivirus that causes significant economic losses to the Chinese poultry industry. Our previous experiments demonstrated that ATMUV infection effectively triggered host innate immune response through MDA5 and TLR3-dependent signaling pathways. However, little information is available on the role of interferon-stimulated genes (ISGs) in defending against ATMUV infection. In this study, we found that ATMUV infection induced robust expression of type I and type III interferon (IFNs) in duck tissues. Furthermore, we observed that expression of interferon-inducible transmembrane proteins (IFITMs) was significantly upregulated in DEF and DF-1 cells after infection with ATMUV. Similar results were obtained from in vivo studies using ATMUV-infected ducklings. Importantly, we showed that knockdown of endogenous IFITM1 or IFITM3 by specific shRNA markedly enhanced ATMUV replication in DF-1 cells. However, disruption of IFITM2 expression had no obvious effect on the ATMUV replication. In addition, overexpression of chicken or duck IFITM1 and IFITM3 in DF-1 cells impaired the replication of ATMUV. Taken together, these results reveal that induced expression of avian IFITM1 and IFITM3 in response to ATMUV infection can effectively restrict the virus replication, and suggest that increasing IFITM proteins in host may be a useful strategy for control of ATMUV infection.",2017 Apr 20,"['Chen, Shilong', 'Wang, Long', 'Chen, Jieying', 'Zhang, Lanlan', 'Wang, Song', 'Goraya, Mohsan U.', 'Chi, Xiaojuan', 'Na, Yang', 'Shao, Wenhan', 'Yang, Zhou', 'Zeng, Xiancheng', 'Chen, Shaoying', 'Chen, Ji-Long']",Front Microbiol,,,True
5e58ef2fc3058da627802377e2b2441149d29c19,PMC,Two Sides of Emotion: Exploring Positivity and Negativity in Six Basic Emotions across Cultures,http://dx.doi.org/10.3389/fpsyg.2017.00610,PMC5397534,28473791,CC BY,"We employ a novel paradigm to test whether six basic emotions (sadness, fear, disgust, anger, surprise, and happiness; Ekman, 1992) contain both negativity and positivity, as opposed to consisting of a single continuum between negative and positive. We examined the perceived negativity and positivity of these emotions in terms of their affective and cognitive components among Korean, Chinese, Canadian, and American students. Assessing each emotion at the cognitive and affective levels cross-culturally provides a fairly comprehensive picture of the positivity and negativity of emotions. Affective components were rated as more divergent than cognitive components. Cross-culturally, Americans and Canadians gave higher valence ratings to the salient valence of each emotion, and lower ratings to the non-salient valence of an emotion, compared to Chinese and Koreans. The results suggest that emotions encompass both positivity and negativity, and there were cross-cultural differences in reported emotions. This paradigm complements existing emotion theories, building on past research and allowing for more parsimonious explanations of cross-cultural research on emotion.",2017 Apr 20,"['An, Sieun', 'Ji, Li-Jun', 'Marks, Michael', 'Zhang, Zhiyong']",Front Psychol,,,True
0acc757154434d8afc870e55c010962a61cc0af3,PMC,Internal control for real-time polymerase chain reaction based on MS2 bacteriophage for RNA viruses diagnostics,http://dx.doi.org/10.1590/0074-02760160380,PMC5398160,28403327,CC BY,"BACKGROUND: Real-time reverse transcription polymerase chain reaction (RT-PCR) is routinely used to detect viral infections. In Brazil, it is mandatory the use of nucleic acid tests to detect hepatitis C virus (HCV), hepatitis B virus and human immunodeficiency virus in blood banks because of the immunological window. The use of an internal control (IC) is necessary to differentiate the true negative results from those consequent from a failure in some step of the nucleic acid test. OBJECTIVES: The aim of this study was the construction of virus-modified particles, based on MS2 bacteriophage, to be used as IC for the diagnosis of RNA viruses. METHODS: The MS2 genome was cloned into the pET47b(+) plasmid, generating pET47b(+)-MS2. MS2-like particles were produced through the synthesis of MS2 RNA genome by T7 RNA polymerase. These particles were used as non-competitive IC in assays for RNA virus diagnostics. In addition, a competitive control for HCV diagnosis was developed by cloning a mutated HCV sequence into the MS2 replicase gene of pET47b(+)-MS2, which produces a non-propagating MS2 particle. The utility of MS2-like particles as IC was evaluated in a one-step format multiplex real-time RT-PCR for HCV detection. FINDINGS: We demonstrated that both competitive and non-competitive IC could be successfully used to monitor the HCV amplification performance, including the extraction, reverse transcription, amplification and detection steps, without compromising the detection of samples with low target concentrations. In conclusion, MS2-like particles generated by this strategy proved to be useful IC for RNA virus diagnosis, with advantage that they are produced by a low cost protocol. An attractive feature of this system is that it allows the construction of a multicontrol by the insertion of sequences from more than one pathogen, increasing its applicability for diagnosing different RNA viruses.",2017 May 6,"['Zambenedetti, Miriam Ribas', 'Pavoni, Daniela Parada', 'Dallabona, Andreia Cristine', 'Dominguez, Alejandro Correa', 'Poersch, Celina de Oliveira', 'Fragoso, Stenio Perdigão', 'Krieger, Marco Aurélio']",Mem Inst Oswaldo Cruz,,,True
0ee2711b5a2409a47565fc475c2fbc726ad3eb90,PMC,Internal control for real-time polymerase chain reaction based on MS2 bacteriophage for RNA viruses diagnostics,http://dx.doi.org/10.1590/0074-02760160380,PMC5398160,28403327,CC BY,"BACKGROUND: Real-time reverse transcription polymerase chain reaction (RT-PCR) is routinely used to detect viral infections. In Brazil, it is mandatory the use of nucleic acid tests to detect hepatitis C virus (HCV), hepatitis B virus and human immunodeficiency virus in blood banks because of the immunological window. The use of an internal control (IC) is necessary to differentiate the true negative results from those consequent from a failure in some step of the nucleic acid test. OBJECTIVES: The aim of this study was the construction of virus-modified particles, based on MS2 bacteriophage, to be used as IC for the diagnosis of RNA viruses. METHODS: The MS2 genome was cloned into the pET47b(+) plasmid, generating pET47b(+)-MS2. MS2-like particles were produced through the synthesis of MS2 RNA genome by T7 RNA polymerase. These particles were used as non-competitive IC in assays for RNA virus diagnostics. In addition, a competitive control for HCV diagnosis was developed by cloning a mutated HCV sequence into the MS2 replicase gene of pET47b(+)-MS2, which produces a non-propagating MS2 particle. The utility of MS2-like particles as IC was evaluated in a one-step format multiplex real-time RT-PCR for HCV detection. FINDINGS: We demonstrated that both competitive and non-competitive IC could be successfully used to monitor the HCV amplification performance, including the extraction, reverse transcription, amplification and detection steps, without compromising the detection of samples with low target concentrations. In conclusion, MS2-like particles generated by this strategy proved to be useful IC for RNA virus diagnosis, with advantage that they are produced by a low cost protocol. An attractive feature of this system is that it allows the construction of a multicontrol by the insertion of sequences from more than one pathogen, increasing its applicability for diagnosing different RNA viruses.",2017 May 6,"['Zambenedetti, Miriam Ribas', 'Pavoni, Daniela Parada', 'Dallabona, Andreia Cristine', 'Dominguez, Alejandro Correa', 'Poersch, Celina de Oliveira', 'Fragoso, Stenio Perdigão', 'Krieger, Marco Aurélio']",Mem Inst Oswaldo Cruz,,,False
f5080088701ed43effa979603627b2a3ad53d5aa,PMC,Type I and Type III Interferons Display Different Dependency on Mitogen-Activated Protein Kinases to Mount an Antiviral State in the Human Gut,http://dx.doi.org/10.3389/fimmu.2017.00459,PMC5399069,28484457,CC BY,"Intestinal epithelial cells (IECs) are constantly exposed to commensal flora and pathogen challenges. How IECs regulate their innate immune response to maintain gut homeostasis remains unclear. Interferons (IFNs) are cytokines produced during infections. While type I IFN receptors are ubiquitously expressed, type III IFN receptors are expressed only on epithelial cells. This epithelium specificity strongly suggests exclusive functions at epithelial surfaces, but the relative roles of type I and III IFNs in the establishment of an antiviral innate immune response in human IECs are not clearly defined. Here, we used mini-gut organoids to define the functions of types I and III IFNs to protect the human gut against viral infection. We show that primary non-transformed human IECs, upon viral challenge, upregulate the expression of both type I and type III IFNs at the transcriptional level but only secrete type III IFN in the supernatant. However, human IECs respond to both type I and type III IFNs by producing IFN-stimulated genes that in turn induce an antiviral state. Using genetic ablation of either type I or type III IFN receptors, we show that either IFN can independently restrict virus infection in human IECs. Importantly, we report, for the first time, differences in the mechanisms by which each IFN establishes the antiviral state. Contrary to type I IFN, the antiviral activity induced by type III IFN is strongly dependent on the mitogen-activated protein kinases signaling pathway, suggesting a pathway used by type III IFNs that non-redundantly contributes to the antiviral state. In conclusion, we demonstrate that human intestinal epithelial cells specifically regulate their innate immune response favoring type III IFN-mediated signaling, which allows for efficient protection against pathogens without producing excessive inflammation. Our results strongly suggest that type III IFN constitutes the frontline of antiviral response in the human gut. We propose that mucosal surfaces, particularly the gastrointestinal tract, have evolved to favor type III IFN-mediated response to pathogen infections as it allows for spatial segregation of signaling and moderate production of inflammatory signals which we propose are key to maintain gut homeostasis.",2017 Apr 21,"['Pervolaraki, Kalliopi', 'Stanifer, Megan L.', 'Münchau, Stephanie', 'Renn, Lynnsey A.', 'Albrecht, Dorothee', 'Kurzhals, Stefan', 'Senís, Elena', 'Grimm, Dirk', 'Schröder-Braunstein, Jutta', 'Rabin, Ronald L.', 'Boulant, Steeve']",Front Immunol,,,True
7267644046c69d176e889933002a9c8819751ff8,PMC,Comprehensive assessment showed no associations of variants at the SLC10A1 locus with susceptibility to persistent HBV infection among Southern Chinese,http://dx.doi.org/10.1038/srep46490,PMC5399367,28429786,CC BY,"The sodium taurocholate cotransporting polypeptide (NTCP) encoded by SLC10A1 was recently demonstrated to be a functional receptor for hepatitis B virus (HBV). The role of SLC10A1 polymorphisms, particularly the Ser267Phe variant (rs2296651) in exon 4, has been frequently investigated in regard to risk of persistent HBV infection. However, these investigations have generated conflicting results. To examine whether common genetic variation at the SLC10A1 locus is associated with risk of persistent HBV infection, haplotype-tagging and imputed single nucleotide polymorphisms (SNPs) were assessed in two case-control sample sets, totally including 2,550 cases (persistently HBV infected subjects, PIs) and 2,124 controls (spontaneously recovered subjects, SRs) of Southern Chinese ancestry. To test whether rare or subpolymorphic SLC10A1 variants are associated with disease risk, the gene’s exons in 244 cases were sequenced. Overall, we found neither SNPs nor haplotypes of SLC10A1 showed significant association in the two sample sets. Furthermore, no significant associations of rare variants or copy number variation covering SLC10A1 were observed. Finally, expression quantitative trait locus analyses revealed that SNPs potentially affecting SLC10A1 expression also showed no significant associations. We conclude that genetic variation at the SLC10A1 locus is not likely a major risk factor of persistent HBV infection among Southern Chinese.",2017 Apr 21,"['Zhang, Ying', 'Li, Yuanfeng', 'Wu, Miantao', 'Cao, Pengbo', 'Liu, Xiaomin', 'Ren, Qian', 'Zhai, Yun', 'Xie, Bobo', 'Hu, Yanling', 'Hu, Zhibin', 'Bei, Jinxin', 'Ping, Jie', 'Liu, Xinyi', 'Yu, Yinghua', 'Guo, Bingqian', 'Lu, Hui', 'Liu, Guanjun', 'Zhang, Haitao', 'Cui, Ying', 'Mo, Zengnan', 'Shen, Hongbing', 'Zeng, Yi-Xin', 'He, Fuchu', 'Zhang, Hongxing', 'Zhou, Gangqiao']",Sci Rep,,,True
62a1e6c2b68e6b09f43596a71ba1546dec37711e,PMC,Comprehensive assessment showed no associations of variants at the SLC10A1 locus with susceptibility to persistent HBV infection among Southern Chinese,http://dx.doi.org/10.1038/srep46490,PMC5399367,28429786,CC BY,"The sodium taurocholate cotransporting polypeptide (NTCP) encoded by SLC10A1 was recently demonstrated to be a functional receptor for hepatitis B virus (HBV). The role of SLC10A1 polymorphisms, particularly the Ser267Phe variant (rs2296651) in exon 4, has been frequently investigated in regard to risk of persistent HBV infection. However, these investigations have generated conflicting results. To examine whether common genetic variation at the SLC10A1 locus is associated with risk of persistent HBV infection, haplotype-tagging and imputed single nucleotide polymorphisms (SNPs) were assessed in two case-control sample sets, totally including 2,550 cases (persistently HBV infected subjects, PIs) and 2,124 controls (spontaneously recovered subjects, SRs) of Southern Chinese ancestry. To test whether rare or subpolymorphic SLC10A1 variants are associated with disease risk, the gene’s exons in 244 cases were sequenced. Overall, we found neither SNPs nor haplotypes of SLC10A1 showed significant association in the two sample sets. Furthermore, no significant associations of rare variants or copy number variation covering SLC10A1 were observed. Finally, expression quantitative trait locus analyses revealed that SNPs potentially affecting SLC10A1 expression also showed no significant associations. We conclude that genetic variation at the SLC10A1 locus is not likely a major risk factor of persistent HBV infection among Southern Chinese.",2017 Apr 21,"['Zhang, Ying', 'Li, Yuanfeng', 'Wu, Miantao', 'Cao, Pengbo', 'Liu, Xiaomin', 'Ren, Qian', 'Zhai, Yun', 'Xie, Bobo', 'Hu, Yanling', 'Hu, Zhibin', 'Bei, Jinxin', 'Ping, Jie', 'Liu, Xinyi', 'Yu, Yinghua', 'Guo, Bingqian', 'Lu, Hui', 'Liu, Guanjun', 'Zhang, Haitao', 'Cui, Ying', 'Mo, Zengnan', 'Shen, Hongbing', 'Zeng, Yi-Xin', 'He, Fuchu', 'Zhang, Hongxing', 'Zhou, Gangqiao']",Sci Rep,,,False
2f446f5b176d426f14b28a4898d83c43291ae82d,PMC,Vaccination with recombinant adenovirus expressing multi-stage antigens of Toxoplasma gondii by the mucosal route induces higher systemic cellular and local mucosal immune responses than with other vaccination routes,http://dx.doi.org/10.1051/parasite/2017013,PMC5399536,28367800,CC BY,"Toxoplasmosis caused by Toxoplasma gondii, an obligate intracellular protozoan, is a cause of congenital disease and abortion in humans and animals. Various vaccination strategies against toxoplasmosis in rodent models have been used in the past few decades; however, effective vaccines remain a challenge. A recombinant adenovirus vaccine expressing ubiquitin-conjugated multi-stage antigen segments (Ad-UMAS) derived from different life-cycle stages of T. gondii was constructed previously. Here, we compared the immune responses and protection effects in vaccination of mice with Ad-UMAS by five vaccination routes including intramuscular (i.m.), intravenous (i.v.), subcutaneous (s.c.), intraoral (i.o.), and intranasal (i.n.). Much higher levels of T. gondii-specific IgG and IgA antibodies were detected in the sera of the intraoral and intranasal vaccination groups on day 49 compared with controls (p < 0.05). The percentages of CD8(+) T-cells in mice immunized intranasally and intraorally were larger than in mice immunized intramuscularly (p < 0.05). The highest level of IL-2 and IFN-γ was detected in the group with nasal immunization, and splenocyte proliferation activity was significantly enhanced in mice immunized via the oral and nasal routes. Furthermore, the higher survival rate (50%) and lower cyst numbers observed in the intraoral and intranasal groups all indicate that Ad-UMAS is far more effective in protecting mice against T. gondii infection via the mucosal route. Ad-UMAS could be an effective and safe mucosal candidate vaccine to protect animals and humans against T. gondii infection.",,"['Wang, Ting', 'Yin, Huiquan', 'Li, Yan', 'Zhao, Lingxiao', 'Sun, Xiahui', 'Cong, Hua']",Parasite.; 24:12,,,True
f22bc1c655de9adc805c72dcccbb9ca43dc2ee5a,PMC,Transmission patterns and evolution of respiratory syncytial virus in a community outbreak identified by genomic analysis,http://dx.doi.org/10.1093/ve/vex006,PMC5399923,28458916,CC BY,"Detailed information on the source, spread and evolution of respiratory syncytial virus (RSV) during seasonal community outbreaks remains sparse. Molecular analyses of attachment (G) gene sequences from hospitalized cases suggest that multiple genotypes and variants co-circulate during epidemics and that RSV persistence over successive seasons is characterized by replacement and multiple new introductions of variants. No studies have defined the patterns of introduction, spread and evolution of RSV at the local community and household level. We present a whole genome sequence analysis of 131 RSV group A viruses collected during 6-month household-based RSV infection surveillance in Coastal Kenya, 2010 within an area of 12 km(2). RSV infections were identified by regular symptom-independent screening of all household members twice weekly. Phylogenetic analysis revealed that the RSV A viruses in nine households were closely related to genotype GA2 and fell within a single branch of the global phylogeny. Genomic analysis allowed the detection of household-specific variation in seven households. For comparison, using only G gene analysis, household-specific variation was found only in one of the nine households. Nucleotide changes were observed both intra-host (viruses identified from same individual in follow-up sampling) and inter-host (viruses identified from different household members) and these coupled with sampling dates enabled a partial reconstruction of the within household transmission chains. The genomic evolutionary rate for the household dataset was estimated as 2.307 × 10 (−) (3) (95% highest posterior density: 0.935–4.165× 10 (−) (3)) substitutions/site/year. We conclude that (i) at the household level, most RSV infections arise from the introduction of a single virus variant followed by accumulation of household specific variation and (ii) analysis of complete virus genomes is crucial to better understand viral transmission in the community. A key question arising is whether prevention of RSV introduction or spread within the household by vaccinating key transmitting household members would lead to a reduced onward community-wide transmission.",2017 Mar 11,"['Agoti, Charles N.', 'Munywoki, Patrick K.', 'Phan, My V. T.', 'Otieno, James R.', 'Kamau, Everlyn', 'Bett, Anne', 'Kombe, Ivy', 'Githinji, George', 'Medley, Graham F.', 'Cane, Patricia A.', 'Kellam, Paul', 'Cotten, Matthew', 'Nokes, D. James']",Virus Evol,,,True
f25b21b722b903a8c39cacc161b1f23fbbdf3c74,PMC,Transmission patterns and evolution of respiratory syncytial virus in a community outbreak identified by genomic analysis,http://dx.doi.org/10.1093/ve/vex006,PMC5399923,28458916,CC BY,"Detailed information on the source, spread and evolution of respiratory syncytial virus (RSV) during seasonal community outbreaks remains sparse. Molecular analyses of attachment (G) gene sequences from hospitalized cases suggest that multiple genotypes and variants co-circulate during epidemics and that RSV persistence over successive seasons is characterized by replacement and multiple new introductions of variants. No studies have defined the patterns of introduction, spread and evolution of RSV at the local community and household level. We present a whole genome sequence analysis of 131 RSV group A viruses collected during 6-month household-based RSV infection surveillance in Coastal Kenya, 2010 within an area of 12 km(2). RSV infections were identified by regular symptom-independent screening of all household members twice weekly. Phylogenetic analysis revealed that the RSV A viruses in nine households were closely related to genotype GA2 and fell within a single branch of the global phylogeny. Genomic analysis allowed the detection of household-specific variation in seven households. For comparison, using only G gene analysis, household-specific variation was found only in one of the nine households. Nucleotide changes were observed both intra-host (viruses identified from same individual in follow-up sampling) and inter-host (viruses identified from different household members) and these coupled with sampling dates enabled a partial reconstruction of the within household transmission chains. The genomic evolutionary rate for the household dataset was estimated as 2.307 × 10 (−) (3) (95% highest posterior density: 0.935–4.165× 10 (−) (3)) substitutions/site/year. We conclude that (i) at the household level, most RSV infections arise from the introduction of a single virus variant followed by accumulation of household specific variation and (ii) analysis of complete virus genomes is crucial to better understand viral transmission in the community. A key question arising is whether prevention of RSV introduction or spread within the household by vaccinating key transmitting household members would lead to a reduced onward community-wide transmission.",2017 Mar 11,"['Agoti, Charles N.', 'Munywoki, Patrick K.', 'Phan, My V. T.', 'Otieno, James R.', 'Kamau, Everlyn', 'Bett, Anne', 'Kombe, Ivy', 'Githinji, George', 'Medley, Graham F.', 'Cane, Patricia A.', 'Kellam, Paul', 'Cotten, Matthew', 'Nokes, D. James']",Virus Evol,,,False
f10e409ed733f8ca5e49e4ebd0482663328f2267,PMC,Expression Dynamics of Innate Immunity in Influenza Virus-Infected Swine,http://dx.doi.org/10.3389/fvets.2017.00048,PMC5399951,28484702,CC BY,"The current circulating swine influenza virus (IV) subtypes in Europe (H1N1, H1N2, and H3N2) are associated with clinical outbreaks of disease. However, we showed that pigs could be susceptible to other IV strains that are able to cross the species barrier. In this work, we extended our investigations into whether different IV strains able to cross the species barrier might give rise to different innate immune responses that could be associated with pathological lesions. For this purpose, we used the same samples collected in a previous study of ours, in which healthy pigs had been infected with a H3N2 Swine IV and four different H3N8 IV strains circulating in different animal species. Pigs had been clinically inspected and four subjects/group were sacrificed at 3, 6, and 21 days post infection. In the present study, all groups but mock exhibited antibody responses to IV nucleoprotein protein. Pulmonary lesions and high-titered viral replication were observed in pigs infected with the swine-adapted virus. Interestingly, pigs infected with avian and seal H3N8 strains also showed moderate lesions and viral replication, whereas equine and canine IVs did not cause overt pathological signs, and replication was barely detectable. Swine IV infection induced interferon (IFN)-alpha and interleukin-6 responses in bronchoalveolar fluids (BALF) at day 3 post infection, as opposed to the other non-swine-adapted virus strains. However, IFN-alpha responses to the swine-adapted virus were not associated with an increase of the local, constitutive expression of IFN-alpha genes. Remarkably, the Equine strain gave rise to a Serum Amyloid A response in BALF despite little if any replication. Each virus strain could be associated with expression of cytokine genes and/or proteins after infection. These responses were observed well beyond the period of virus replication, suggesting a prolonged homeostatic imbalance of the innate immune system.",2017 Apr 21,"['Montoya, María', 'Foni, Emanuela', 'Solórzano, Alicia', 'Razzuoli, Elisabetta', 'Baratelli, Massimiliano', 'Bilato, Dania', 'Córdoba, Lorena', 'del Burgo, Maria Angeles Martín', 'Martinez, Jorge', 'Martinez-Orellana, Pamela', 'Chiapponi, Chiara', 'Perlin, David S.', 'del Real, Gustavo', 'Amadori, Massimo']",Front Vet Sci,,,True
81cc511fb2f42c6f79346aab7b1277ee0a6e78a7,PMC,"Prevalence, diversity, and host associations of Bartonella strains in bats from Georgia (Caucasus)",http://dx.doi.org/10.1371/journal.pntd.0005428,PMC5400274,28399125,CC0,"Bartonella infections were investigated in seven species of bats from four regions of the Republic of Georgia. Of the 236 bats that were captured, 212 (90%) specimens were tested for Bartonella infection. Colonies identified as Bartonella were isolated from 105 (49.5%) of 212 bats Phylogenetic analysis based on sequence variation of the gltA gene differentiated 22 unique Bartonella genogroups. Genetic distances between these diverse genogroups were at the level of those observed between different Bartonella species described previously. Twenty-one reference strains from 19 representative genogroups were characterized using four additional genetic markers. Host specificity to bat genera or families was reported for several Bartonella genogroups. Some Bartonella genotypes found in bats clustered with those identified in dogs from Thailand and humans from Poland.",2017 Apr 11,"['Urushadze, Lela', 'Bai, Ying', 'Osikowicz, Lynn', 'McKee, Clifton', 'Sidamonidze, Ketevan', 'Putkaradze, Davit', 'Imnadze, Paata', 'Kandaurov, Andrei', 'Kuzmin, Ivan', 'Kosoy, Michael']",PLoS Negl Trop Dis,,,True
10ce102dd3c76f690ebe84048a5d734598b3d2f1,PMC,Social media engagement analysis of U.S. Federal health agencies on Facebook,http://dx.doi.org/10.1186/s12911-017-0447-z,PMC5401385,28431582,CC BY,"BACKGROUND: It is becoming increasingly common for individuals and organizations to use social media platforms such as Facebook. These are being used for a wide variety of purposes including disseminating, discussing and seeking health related information. U.S. Federal health agencies are leveraging these platforms to ‘engage’ social media users to read, spread, promote and encourage health related discussions. However, different agencies and their communications get varying levels of engagement. In this study we use statistical models to identify factors that associate with engagement. METHODS: We analyze over 45,000 Facebook posts from 72 Facebook accounts belonging to 24 health agencies. Account usage, user activity, sentiment and content of these posts are studied. We use the hurdle regression model to identify factors associated with the level of engagement and Cox proportional hazards model to identify factors associated with duration of engagement. RESULTS: In our analysis we find that agencies and accounts vary widely in their usage of social media and activity they generate. Statistical analysis shows, for instance, that Facebook posts with more visual cues such as photos or videos or those which express positive sentiment generate more engagement. We further find that posts on certain topics such as occupation or organizations negatively affect the duration of engagement. CONCLUSIONS: We present the first comprehensive analyses of engagement with U.S. Federal health agencies on Facebook. In addition, we briefly compare and contrast findings from this study to our earlier study with similar focus but on Twitter to show the robustness of our methods.",2017 Apr 21,"['Bhattacharya, Sanmitra', 'Srinivasan, Padmini', 'Polgreen, Philip']",BMC Med Inform Decis Mak,,,True
7859dc5bc2c21103513a0d3d27e148496c2c617c,PMC,Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats,http://dx.doi.org/10.1155/2017/3102567,PMC5401735,28492060,CC BY,"A Target Animal Safety protocol was used to examine adverse events in male and female Fischer F344/NTac rats treated with increasing doses of a subcutaneous implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of drug for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Approximately 25% of a cohort of rats given the excess doses of 1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of intermittent and limited excess grooming and self-gnawing. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery of buprenorphine in laboratory animals and further demonstrate the utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug therapy.",2017 Apr 9,"['Guarnieri, M.', 'Brayton, C.', 'Sarabia-Estrada, R.', 'Tyler, B.', 'McKnight, P.', 'DeTolla, L.']",J Vet Med,,,True
907094f2d7dba9a0cab6c5b0aa566ff69d124f02,PMC,Perception and Attitude of Emergency Room Resident Physicians toward Middle East Respiratory Syndrome Outbreak,http://dx.doi.org/10.1155/2017/6978256,PMC5402244,28487774,CC BY,"Introduction. Middle East respiratory syndrome (MERS) outbreaks have had a considerable negative impact on health systems in Saudi Arabia. We aimed to study the psychological impact of a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak on emergency room resident physicians (ERRPs). Methods. We assessed the MERS-related psychological impact and concerns of ERRPs using a self-report questionnaire. Results. The majority (91%) of the ERRPs agreed that their work put them at risk of infection, but most (65%) did not agree that they should not be looking after patients infected with MERS. Despite that, 54% of ERRPs reported being afraid of contracting the infection from infected patients and only 4.2% of them were willing to change their current job. The majority of the ERRPs (85%) felt that their job would expose their families to risk of infection. Conclusions. Our study demonstrated the considerable psychological impact of MERS outbreaks on ERRPs. The ERRPs' concerns and the psychological impact of MERS outbreaks should be considered in greater detail by hospital policymakers.",2017 Apr 10,"['Al Ghobain, Mohammed', 'Aldrees, Turki', 'Alenezi, Abdullah', 'Alqaryan, Saleh', 'Aldabeeb, Dana', 'Alotaibi, Najed', 'Aldhabib, Abdulrahman', 'Alghalibi, Shaker', 'Alharethy, Sami']",Emerg Med Int,,,True
105eabe3e019ae2bb0f93493d7f43d2c1c19e4c5,PMC,Fasciola hepatica glycoconjugates immuneregulate dendritic cells through the Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin inducing T cell anergy,http://dx.doi.org/10.1038/srep46748,PMC5402274,28436457,CC BY,"Dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) expressed on a variety of DCs, is a C-type lectin receptor that recognizes glycans on a diverse range of pathogens, including parasites. The interaction of DC-SIGN with pathogens triggers specific signaling events that modulate DC-maturation and activity and regulate T-cell activation by DCs. In this work we evaluate whether F. hepatica glycans can immune modulate DCs via DC-SIGN. We demonstrate that DC-SIGN interacts with F. hepatica glycoconjugates through mannose and fucose residues. We also show that mannose is present in high-mannose structures, hybrid and trimannosyl N-glycans with terminal GlcNAc. Furthermore, we demonstrate that F. hepatica glycans induce DC-SIGN triggering leading to a strong production of TLR-induced IL-10 and IL-27p28. In addition, parasite glycans induced regulatory DCs via DC-SIGN that decrease allogeneic T cell proliferation, via the induction of anergic/regulatory T cells, highlighting the role of DC-SIGN in the regulation of innate and adaptive immune responses by F. hepatica. Our data confirm the immunomodulatory properties of DC-SIGN triggered by pathogen-derived glycans and contribute to the identification of immunomodulatory glyans of helminths that might eventually be useful for the design of vaccines against fasciolosis.",2017 Apr 24,"['Rodríguez, Ernesto', 'Kalay, Hakan', 'Noya, Verónica', 'Brossard, Natalie', 'Giacomini, Cecilia', 'van Kooyk, Yvette', 'García-Vallejo, Juan J.', 'Freire, Teresa']",Sci Rep,,,True
098d02cb0e1978a1e2ac6557d65895e4d2041e1e,PMC,Fasciola hepatica glycoconjugates immuneregulate dendritic cells through the Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin inducing T cell anergy,http://dx.doi.org/10.1038/srep46748,PMC5402274,28436457,CC BY,"Dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) expressed on a variety of DCs, is a C-type lectin receptor that recognizes glycans on a diverse range of pathogens, including parasites. The interaction of DC-SIGN with pathogens triggers specific signaling events that modulate DC-maturation and activity and regulate T-cell activation by DCs. In this work we evaluate whether F. hepatica glycans can immune modulate DCs via DC-SIGN. We demonstrate that DC-SIGN interacts with F. hepatica glycoconjugates through mannose and fucose residues. We also show that mannose is present in high-mannose structures, hybrid and trimannosyl N-glycans with terminal GlcNAc. Furthermore, we demonstrate that F. hepatica glycans induce DC-SIGN triggering leading to a strong production of TLR-induced IL-10 and IL-27p28. In addition, parasite glycans induced regulatory DCs via DC-SIGN that decrease allogeneic T cell proliferation, via the induction of anergic/regulatory T cells, highlighting the role of DC-SIGN in the regulation of innate and adaptive immune responses by F. hepatica. Our data confirm the immunomodulatory properties of DC-SIGN triggered by pathogen-derived glycans and contribute to the identification of immunomodulatory glyans of helminths that might eventually be useful for the design of vaccines against fasciolosis.",2017 Apr 24,"['Rodríguez, Ernesto', 'Kalay, Hakan', 'Noya, Verónica', 'Brossard, Natalie', 'Giacomini, Cecilia', 'van Kooyk, Yvette', 'García-Vallejo, Juan J.', 'Freire, Teresa']",Sci Rep,,,False
c5139e673b41fa64eb80936bc9d63e83bf3c7172,PMC,Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals,http://dx.doi.org/10.1038/srep46557,PMC5402285,28436427,CC BY,"Broadly Cross clade Neutralizing (BCN) antibodies are recognized as potential therapeutic tools and leads for the design of a vaccine that can protect human beings against various clades of Human Immunodeficiency Virus (HIV). In the present study, we screened plasma of 88 HIV-1 infected ART naïve individuals for their neutralization potential using a standard panel of 18 pseudoviruses belonging to different subtypes and different levels of neutralization. We identified 12 samples with good breadth of neutralization (neutralized >90% of the viruses). Four of these samples neutralized even the difficult-to-neutralize tier-3 pseudoviruses with great potency (GMT > 600). Analysis of neutralization specificities indicated that four samples had antibodies with multiple epitope binding specificities, viz. CD4-binding site (CD4BS), glycans in the V1/V2 and V3 regions and membrane proximal external region (MPER). Our findings indicate the strong possibility of identifying highly potent bNAbs with known or novel specificities from HIV-1 subtype C infected individuals from India that can be exploited as therapeutic tools or lead molecules for the identification of potential epitopes for design of a protective HIV-1 vaccine.",2017 Apr 24,"['Cheedarla, Narayanaiah', 'Precilla, K. Lucia', 'Babu, Hemalatha', 'Vijayan, K. K. Vidya', 'Ashokkumar, Manickam', 'Chandrasekaran, Padmapriyadarsini', 'Kailasam, Nandagopal', 'Sundaramurthi, Jagadish Chandrabose', 'Swaminathan, Soumya', 'Buddolla, Viswanath', 'Vaniambadi, S. Kalyanaraman', 'Ramanathan, V. D.', 'Hanna, Luke Elizabeth']",Sci Rep,,,True
7b37e950f59962c2fde64154be3cfe3ba47499af,PMC,Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals,http://dx.doi.org/10.1038/srep46557,PMC5402285,28436427,CC BY,"Broadly Cross clade Neutralizing (BCN) antibodies are recognized as potential therapeutic tools and leads for the design of a vaccine that can protect human beings against various clades of Human Immunodeficiency Virus (HIV). In the present study, we screened plasma of 88 HIV-1 infected ART naïve individuals for their neutralization potential using a standard panel of 18 pseudoviruses belonging to different subtypes and different levels of neutralization. We identified 12 samples with good breadth of neutralization (neutralized >90% of the viruses). Four of these samples neutralized even the difficult-to-neutralize tier-3 pseudoviruses with great potency (GMT > 600). Analysis of neutralization specificities indicated that four samples had antibodies with multiple epitope binding specificities, viz. CD4-binding site (CD4BS), glycans in the V1/V2 and V3 regions and membrane proximal external region (MPER). Our findings indicate the strong possibility of identifying highly potent bNAbs with known or novel specificities from HIV-1 subtype C infected individuals from India that can be exploited as therapeutic tools or lead molecules for the identification of potential epitopes for design of a protective HIV-1 vaccine.",2017 Apr 24,"['Cheedarla, Narayanaiah', 'Precilla, K. Lucia', 'Babu, Hemalatha', 'Vijayan, K. K. Vidya', 'Ashokkumar, Manickam', 'Chandrasekaran, Padmapriyadarsini', 'Kailasam, Nandagopal', 'Sundaramurthi, Jagadish Chandrabose', 'Swaminathan, Soumya', 'Buddolla, Viswanath', 'Vaniambadi, S. Kalyanaraman', 'Ramanathan, V. D.', 'Hanna, Luke Elizabeth']",Sci Rep,,,False
18a8af7a7be62a2ccc66a4f65c94ac94bf2f8639,PMC,Association between genetic polymorphisms of MMP8 and the risk of steroid-induced osteonecrosis of the femoral head in the population of northern China,http://dx.doi.org/10.1097/MD.0000000000004794,PMC5402575,27631232,CC BY,"BACKGROUND: Steroid-induced osteonecrosis of the femoral head (ONFH) is the most common clinical nontraumatic ONFH. Once ONFH occurs, it seriously reduces patients’ quality of life. The matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) system was found to play a significant role in the development of ONFH. The aim of this study was to identify the associations between 7 genes selected from the MMP/TIMP system and steroid-induced ONFH. METHODS: We genotyped 34 single-nucleotide polymorphisms (SNPs) of 7 genes selected from the MMP/TIMP system in a case–control study with 285 cases of steroid-induced ONFH and 308 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the chi-squared test, genetic model analysis, haplotype analysis, and stratification analysis. RESULTS: We found that the minor alleles of rs1940475 and rs11225395 in MMP8 were associated with a 1.32-fold increased risk of steroid-induced ONFH in the allelic model analysis (P = 0.021 and 0.022, respectively). In the genetic model analysis, we found that rs3740938, rs2012390, rs1940475, and rs11225395 were associated with an increased risk of steroid-induced ONFH. In further stratification analysis, rs3740938 and rs2012390 displayed a significantly increased risk of steroid-induced ONFH in females under the dominant (rs3740938, OR = 2.69, 95% CI: 1.50–4.83, P = 0.001; rs2012390, OR = 2.30, 95% CI: 1.31–4.03, P = 0.012) and additive (rs3740938, OR = 2.02, 95% CI: 1.24–3.29, P = 0.010; rs2012390, OR = 1.77, 95% CI: 1.12–2.80, P = 0.047) models. In addition, haplotype “AGTCA” of MMP8 was found to be associated with a 1.40-fold increased risk of steroid-induced ONFH (95% CI: 1.04–1.88, P = 0.025). CONCLUSION: Our results verify that genetic variants of MMP8 contribute to steroid-induced ONFH susceptibility in the population of northern China. In addition, we found that gender differences might interact with MMP8 polymorphisms to contribute to the overall susceptibility to steroid-induced ONFH.",2016 Sep 16,"['Du, Jieli', 'Jin, Tianbo', 'Cao, Yuju', 'Chen, Junyu', 'Guo, Yongchang', 'Sun, Mingqi', 'Li, Jian', 'Zhang, Xiyang', 'Wang, Guoqiang', 'Wang, Jianzhong']",Medicine (Baltimore),,,True
9018234c987db8e1aec9ca3cae1806b75e4835ad,PMC,The phosphatidylinositol-3-phosphate 5-kinase inhibitor apilimod blocks filoviral entry and infection,http://dx.doi.org/10.1371/journal.pntd.0005540,PMC5402990,28403145,CC0,"Phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) is a lipid kinase involved in endosome maturation that emerged from a haploid genetic screen as being required for Ebola virus (EBOV) infection. Here we analyzed the effects of apilimod, a PIKfyve inhibitor that was reported to be well tolerated in humans in phase 2 clinical trials, for its effects on entry and infection of EBOV and Marburg virus (MARV). We first found that apilimod blocks infections by EBOV and MARV in Huh 7, Vero E6 and primary human macrophage cells, with notable potency in the macrophages (IC(50), 10 nM). We next observed that similar doses of apilimod block EBOV-glycoprotein-virus like particle (VLP) entry and transcription-replication competent VLP infection, suggesting that the primary mode of action of apilimod is as an entry inhibitor, preventing release of the viral genome into the cytoplasm to initiate replication. After providing evidence that the anti-EBOV action of apilimod is via PIKfyve, we showed that it blocks trafficking of EBOV VLPs to endolysosomes containing Niemann-Pick C1 (NPC1), the intracellular receptor for EBOV. Concurrently apilimod caused VLPs to accumulate in early endosome antigen 1-positive endosomes. We did not detect any effects of apilimod on bulk endosome acidification, on the activity of cathepsins B and L, or on cholesterol export from endolysosomes. Hence by antagonizing PIKfyve, apilimod appears to block EBOV trafficking to its site of fusion and entry into the cytoplasm. Given the drug’s observed anti-filoviral activity, relatively unexplored mechanism of entry inhibition, and reported tolerability in humans, we propose that apilimod be further explored as part of a therapeutic regimen to treat filoviral infections.",2017 Apr 12,"['Nelson, Elizabeth A.', 'Dyall, Julie', 'Hoenen, Thomas', 'Barnes, Alyson B.', 'Zhou, Huanying', 'Liang, Janie Y.', 'Michelotti, Julia', 'Dewey, William H.', 'DeWald, Lisa Evans', 'Bennett, Richard S.', 'Morris, Patrick J.', 'Guha, Rajarshi', 'Klumpp-Thomas, Carleen', 'McKnight, Crystal', 'Chen, Yu-Chi', 'Xu, Xin', 'Wang, Amy', 'Hughes, Emma', 'Martin, Scott', 'Thomas, Craig', 'Jahrling, Peter B.', 'Hensley, Lisa E.', 'Olinger, Gene G.', 'White, Judith M.']",PLoS Negl Trop Dis,,,True
57debc6d188282301818dada90a7cee441c45379,PMC,Mechanisms of antidiarrhoeal effects by diosmectite in human intestinal cells,http://dx.doi.org/10.1186/s13099-017-0172-2,PMC5404323,28450899,CC BY,"BACKGROUND: Rotavirus (RV) induces diarrhoea through a sequence of enterotoxic and cytotoxic effects. The former are NSP4-dependent, induce calcium-dependent chloride secretion and involve oxidative stress. Diosmectite (DS) is a natural clay that has been recommended as an active therapy for diarrhoea, but the mechanism of its effect is not clear. Electrical parameters may be used to measure the direct enterotoxic and cytotoxic effects in polar epithelial intestinal cells. To investigate the effects of DS on RV-induced enterotoxic and cytotoxic damage. Caco-2 cells were used as a model of RV infection to evaluate chloride secretion, epithelial integrity, oxidative stress and viral infectivity in Ussing chambers. RESULTS: Diosmectite reduced the expression of NSP4 and oxidative stress, resulting in a strong inhibition of chloride secretion. Preincubating RV with DS reduced the cytotoxic effect. Finally, the viral load was reduced by DS but not by control clay. This result suggests that DS specifically affects the early events of RV infection protecting the enterocyte, whereas it does not restore already-established cell damage. CONCLUSION: These findings indicate that DS exerts an anti-diarrhoeal effect by inhibiting viral replication and the expression of NSP4. Both ion secretion and cell damage induced by RV are strongly inhibited consequent to the antiviral effect, which explains its clinical efficacy.",2017 Apr 24,"['Buccigrossi, Vittoria', 'Russo, Carla', 'Guarino, Amedeo', 'de Freitas, Maiara Brusco', 'Guarino, Alfredo']",Gut Pathog,,,True
02049ffbdb20997055c4def3516af0e6e40dd427,PMC,Ribonuclease L mediates the cell-lethal phenotype of double-stranded RNA editing enzyme ADAR1 deficiency in a human cell line,http://dx.doi.org/10.7554/eLife.25687,PMC5404912,28362255,CC BY,"ADAR1 isoforms are adenosine deaminases that edit and destabilize double-stranded RNA reducing its immunostimulatory activities. Mutation of ADAR1 leads to a severe neurodevelopmental and inflammatory disease of children, Aicardi-Goutiéres syndrome. In mice, Adar1 mutations are embryonic lethal but are rescued by mutation of the Mda5 or Mavs genes, which function in IFN induction. However, the specific IFN regulated proteins responsible for the pathogenic effects of ADAR1 mutation are unknown. We show that the cell-lethal phenotype of ADAR1 deletion in human lung adenocarcinoma A549 cells is rescued by CRISPR/Cas9 mutagenesis of the RNASEL gene or by expression of the RNase L antagonist, murine coronavirus NS2 accessory protein. Our result demonstrate that ablation of RNase L activity promotes survival of ADAR1 deficient cells even in the presence of MDA5 and MAVS, suggesting that the RNase L system is the primary sensor pathway for endogenous dsRNA that leads to cell death. DOI: http://dx.doi.org/10.7554/eLife.25687.001",,"['Li, Yize', 'Banerjee, Shuvojit', 'Goldstein, Stephen A', 'Dong, Beihua', 'Gaughan, Christina', 'Rath, Sneha', 'Donovan, Jesse', 'Korennykh, Alexei', 'Silverman, Robert H', 'Weiss, Susan R']",eLife.; 6:e25687,,,True
2e237dc7ffdacf42c76c0671bea72fae2a3ec9e1,PMC,Short-Sighted Virus Evolution and a Germline Hypothesis for Chronic Viral Infections,http://dx.doi.org/10.1016/j.tim.2017.03.003,PMC5405858,28377208,CC BY,"With extremely short generation times and high mutability, many viruses can rapidly evolve and adapt to changing environments. This ability is generally beneficial to viruses as it allows them to evade host immune responses, evolve new behaviours, and exploit ecological niches. However, natural selection typically generates adaptation in response to the immediate selection pressures that a virus experiences in its current host. Consequently, we argue that some viruses, particularly those characterised by long durations of infection and ongoing replication, may be susceptible to short-sighted evolution, whereby a virus’ adaptation to its current host will be detrimental to its onward transmission within the host population. Here we outline the concept of short-sighted viral evolution and provide examples of how it may negatively impact viral transmission among hosts. We also propose that viruses that are vulnerable to short-sighted evolution may exhibit strategies that minimise its effects. We speculate on the various mechanisms by which this may be achieved, including viral life history strategies that result in low rates of within-host evolution, or the establishment of a ‘germline’ lineage of viruses that avoids short-sighted evolution. These concepts provide a new perspective on the way in which some viruses have been able to establish and maintain global pandemics.",2017 May 1,"['Lythgoe, Katrina A.', 'Gardner, Andy', 'Pybus, Oliver G.', 'Grove, Joe']",Trends Microbiol,,,True
2f568d8ea97b28cffe66f46e6431b347dfa8ca30,PMC,De novo assembly of highly polymorphic metagenomic data using in situ generated reference sequences and a novel BLAST-based assembly pipeline,http://dx.doi.org/10.1186/s12859-017-1630-z,PMC5406902,28446139,CC BY,"BACKGROUND: The accuracy of metagenomic assembly is usually compromised by high levels of polymorphism due to divergent reads from the same genomic region recognized as different loci when sequenced and assembled together. A viral quasispecies is a group of abundant and diversified genetically related viruses found in a single carrier. Current mainstream assembly methods, such as Velvet and SOAPdenovo, were not originally intended for the assembly of such metagenomics data, and therefore demands for new methods to provide accurate and informative assembly results for metagenomic data. RESULTS: In this study, we present a hybrid method for assembling highly polymorphic data combining the partial de novo-reference assembly (PDR) strategy and the BLAST-based assembly pipeline (BBAP). The PDR strategy generates in situ reference sequences through de novo assembly of a randomly extracted partial data set which is subsequently used for the reference assembly for the full data set. BBAP employs a greedy algorithm to assemble polymorphic reads. We used 12 hepatitis B virus quasispecies NGS data sets from a previous study to assess and compare the performance of both PDR and BBAP. Analyses suggest the high polymorphism of a full metagenomic data set leads to fragmentized de novo assembly results, whereas the biased or limited representation of external reference sequences included fewer reads into the assembly with lower assembly accuracy and variation sensitivity. In comparison, the PDR generated in situ reference sequence incorporated more reads into the final PDR assembly of the full metagenomics data set along with greater accuracy and higher variation sensitivity. BBAP assembly results also suggest higher assembly efficiency and accuracy compared to other assembly methods. Additionally, BBAP assembly recovered HBV structural variants that were not observed amongst assembly results of other methods. Together, PDR/BBAP assembly results were significantly better than other compared methods. CONCLUSIONS: Both PDR and BBAP independently increased the assembly efficiency and accuracy of highly polymorphic data, and assembly performances were further improved when used together. BBAP also provides nucleotide frequency information. Together, PDR and BBAP provide powerful tools for metagenomic data studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-017-1630-z) contains supplementary material, which is available to authorized users.",2017 Apr 26,"['Lin, You-Yu', 'Hsieh, Chia-Hung', 'Chen, Jiun-Hong', 'Lu, Xuemei', 'Kao, Jia-Horng', 'Chen, Pei-Jer', 'Chen, Ding-Shinn', 'Wang, Hurng-Yi']",BMC Bioinformatics,,,False
f7b0a4b72da3b040ec9904ad1137e7c5c0eab777,PMC,De novo assembly of highly polymorphic metagenomic data using in situ generated reference sequences and a novel BLAST-based assembly pipeline,http://dx.doi.org/10.1186/s12859-017-1630-z,PMC5406902,28446139,CC BY,"BACKGROUND: The accuracy of metagenomic assembly is usually compromised by high levels of polymorphism due to divergent reads from the same genomic region recognized as different loci when sequenced and assembled together. A viral quasispecies is a group of abundant and diversified genetically related viruses found in a single carrier. Current mainstream assembly methods, such as Velvet and SOAPdenovo, were not originally intended for the assembly of such metagenomics data, and therefore demands for new methods to provide accurate and informative assembly results for metagenomic data. RESULTS: In this study, we present a hybrid method for assembling highly polymorphic data combining the partial de novo-reference assembly (PDR) strategy and the BLAST-based assembly pipeline (BBAP). The PDR strategy generates in situ reference sequences through de novo assembly of a randomly extracted partial data set which is subsequently used for the reference assembly for the full data set. BBAP employs a greedy algorithm to assemble polymorphic reads. We used 12 hepatitis B virus quasispecies NGS data sets from a previous study to assess and compare the performance of both PDR and BBAP. Analyses suggest the high polymorphism of a full metagenomic data set leads to fragmentized de novo assembly results, whereas the biased or limited representation of external reference sequences included fewer reads into the assembly with lower assembly accuracy and variation sensitivity. In comparison, the PDR generated in situ reference sequence incorporated more reads into the final PDR assembly of the full metagenomics data set along with greater accuracy and higher variation sensitivity. BBAP assembly results also suggest higher assembly efficiency and accuracy compared to other assembly methods. Additionally, BBAP assembly recovered HBV structural variants that were not observed amongst assembly results of other methods. Together, PDR/BBAP assembly results were significantly better than other compared methods. CONCLUSIONS: Both PDR and BBAP independently increased the assembly efficiency and accuracy of highly polymorphic data, and assembly performances were further improved when used together. BBAP also provides nucleotide frequency information. Together, PDR and BBAP provide powerful tools for metagenomic data studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-017-1630-z) contains supplementary material, which is available to authorized users.",2017 Apr 26,"['Lin, You-Yu', 'Hsieh, Chia-Hung', 'Chen, Jiun-Hong', 'Lu, Xuemei', 'Kao, Jia-Horng', 'Chen, Pei-Jer', 'Chen, Ding-Shinn', 'Wang, Hurng-Yi']",BMC Bioinformatics,,,True
9e009084059ebea290ba99f450faff6e4372a4c4,PMC,The not-so-infinite malleability of RNA viruses: Viral and cellular determinants of RNA virus mutation rates,http://dx.doi.org/10.1371/journal.ppat.1006254,PMC5407569,28448634,CC BY,,2017 Apr 27,"Smith, Everett Clinton",PLoS Pathog,,,True
6308a19784dd34b796ecd3a981e32c01e866ee03,PMC,Single-Round Infectious Particle Antiviral Screening Assays for the Japanese Encephalitis Virus,http://dx.doi.org/10.3390/v9040076,PMC5408682,28394283,CC BY,"Japanese Encephalitis virus (JEV) is a mosquito-borne flavivirus with a positive-sense single-stranded RNA genome that contains a big open reading frame (ORF) flanked by 5′- and 3′- untranslated regions (UTRs). Nearly 30,000 JE cases with 10,000 deaths are still annually reported in East Asia. Although the JEV genotype III vaccine has been licensed, it elicits a lower protection against other genotypes. Moreover, no effective treatment for a JE case is developed. This study constructed a pBR322-based and cytomegaloviruses (CMV) promoter-driven JEV replicon for the production of JEV single-round infectious particles (SRIPs) in a packaging cell line expressing viral structural proteins. Genetic instability of JEV genome cDNA in the pBR322 plasmid was associated with the prokaryotic promoter at 5′ end of the JEV genome that triggers the expression of the structural proteins in E. coli. JEV structural proteins were toxic E. coli, thus the encoding region for structural proteins was replaced by a reporter gene (enhanced green fluorescent protein, EGFP) that was in-frame fused with the first eight amino acids of the C protein at N-terminus and the foot-and-mouth disease virus (FMDV) 2A peptide at C-terminus in a pBR322-based JEV-EGFP replicon. JEV-EGFP SRIPs generated from JEV-EGFP replicon-transfected packaging cells displayed the infectivity with cytopathic effect induction, self-replication of viral genomes, and the expression of EGFP and viral proteins. Moreover, the combination of JEV-EGFP SRIP plus flow cytometry was used to determine the half maximal inhibitory concentration (IC50) values of antiviral agents according to fluorescent intensity and positivity of SRIP-infected packaging cells post treatment. MJ-47, a quinazolinone derivative, significantly inhibited JEV-induced cytopathic effect, reducing the replication and expression of JEV-EGFP replicon in vitro. The IC50 value of 6.28 µM for MJ-47 against JEV was determined by the assay of JEV-EGFP SRIP infection in packaging cells plus flow cytometry that was more sensitive, effective, and efficient compared to the traditional plaque assay. Therefore, the system of JEV-EGFP SRIPs plus flow cytometry was a rapid and reliable platform for screening antiviral agents and evaluating antiviral potency.",2017 Apr 10,"['Lu, Chien-Yi', 'Hour, Mann-Jen', 'Wang, Ching-Ying', 'Huang, Su-Hua', 'Mu, Wen-Xiang', 'Chang, Yu-Chun', 'Lin, Cheng-Wen']",Viruses,,,True
d075063670ece618e06fc8b9207cd7a6f4d61ed8,PMC,Single-Round Infectious Particle Antiviral Screening Assays for the Japanese Encephalitis Virus,http://dx.doi.org/10.3390/v9040076,PMC5408682,28394283,CC BY,"Japanese Encephalitis virus (JEV) is a mosquito-borne flavivirus with a positive-sense single-stranded RNA genome that contains a big open reading frame (ORF) flanked by 5′- and 3′- untranslated regions (UTRs). Nearly 30,000 JE cases with 10,000 deaths are still annually reported in East Asia. Although the JEV genotype III vaccine has been licensed, it elicits a lower protection against other genotypes. Moreover, no effective treatment for a JE case is developed. This study constructed a pBR322-based and cytomegaloviruses (CMV) promoter-driven JEV replicon for the production of JEV single-round infectious particles (SRIPs) in a packaging cell line expressing viral structural proteins. Genetic instability of JEV genome cDNA in the pBR322 plasmid was associated with the prokaryotic promoter at 5′ end of the JEV genome that triggers the expression of the structural proteins in E. coli. JEV structural proteins were toxic E. coli, thus the encoding region for structural proteins was replaced by a reporter gene (enhanced green fluorescent protein, EGFP) that was in-frame fused with the first eight amino acids of the C protein at N-terminus and the foot-and-mouth disease virus (FMDV) 2A peptide at C-terminus in a pBR322-based JEV-EGFP replicon. JEV-EGFP SRIPs generated from JEV-EGFP replicon-transfected packaging cells displayed the infectivity with cytopathic effect induction, self-replication of viral genomes, and the expression of EGFP and viral proteins. Moreover, the combination of JEV-EGFP SRIP plus flow cytometry was used to determine the half maximal inhibitory concentration (IC50) values of antiviral agents according to fluorescent intensity and positivity of SRIP-infected packaging cells post treatment. MJ-47, a quinazolinone derivative, significantly inhibited JEV-induced cytopathic effect, reducing the replication and expression of JEV-EGFP replicon in vitro. The IC50 value of 6.28 µM for MJ-47 against JEV was determined by the assay of JEV-EGFP SRIP infection in packaging cells plus flow cytometry that was more sensitive, effective, and efficient compared to the traditional plaque assay. Therefore, the system of JEV-EGFP SRIPs plus flow cytometry was a rapid and reliable platform for screening antiviral agents and evaluating antiviral potency.",2017 Apr 10,"['Lu, Chien-Yi', 'Hour, Mann-Jen', 'Wang, Ching-Ying', 'Huang, Su-Hua', 'Mu, Wen-Xiang', 'Chang, Yu-Chun', 'Lin, Cheng-Wen']",Viruses,,,False
9dd7a29452ebf3285c47109ce0c72e2099347622,PMC,"Effects of Fruit and Vegetable Consumption on Risk of Asthma, Wheezing and Immune Responses: A Systematic Review and Meta-Analysis",http://dx.doi.org/10.3390/nu9040341,PMC5409680,28353635,CC BY,"Evidence suggests that reduced intake of fruit and vegetables may play a critical role in the development of asthma and allergies. The present review aimed to summarize the evidence for the association between fruit and vegetable intake, risk of asthma/wheeze and immune responses. Databases including PubMed, Cochrane, CINAHL and EMBASE were searched up to June 2016. Studies that investigated the effects of fruit and vegetable intake on risk of asthma/wheeze and immune responses were considered eligible (n = 58). Studies used cross-sectional (n = 30), cohort (n = 13), case-control (n = 8) and experimental (n = 7) designs. Most of the studies (n = 30) reported beneficial associations of fruit and vegetable consumption with risk of asthma and/or respiratory function, while eight studies found no significant relationship. Some studies (n = 20) reported mixed results, as they found a negative association between fruit only or vegetable only, and asthma. In addition, the meta-analyses in both adults and children showed inverse associations between fruit intake and risk of prevalent wheeze and asthma severity (p < 0.05). Likewise, vegetable intake was negatively associated with risk of prevalent asthma (p < 0.05). Seven studies examined immune responses in relation to fruit and vegetable intake in asthma, with n = 6 showing a protective effect against either systemic or airway inflammation. Fruit and vegetable consumption appears to be protective against asthma.",2017 Mar 29,"['Hosseini, Banafshe', 'Berthon, Bronwyn S.', 'Wark, Peter', 'Wood, Lisa G.']",Nutrients,,,True
4873940c333a45e7913856b356309e2e4feffb7f,PMC,"School absenteeism among school‐aged children with medically attended acute viral respiratory illness during three influenza seasons, 2012‐2013 through 2014‐2015",http://dx.doi.org/10.1111/irv.12440,PMC5410714,27885805,CC BY,"BACKGROUND: Acute respiratory illnesses (ARIs) are common in school‐aged children, but few studies have assessed school absenteeism due to specific respiratory viruses. OBJECTIVE: To evaluate school absenteeism among children with medically attended ARI due to common viruses. METHODS: We analyzed follow‐up surveys from children seeking care for acute respiratory illness who were enrolled in the influenza vaccine effectiveness study at Marshfield Clinic during the 2012‐2013 through 2014‐2015 influenza seasons. Archived influenza‐negative respiratory swabs were retested using multiplex RT‐PCR to detect 16 respiratory virus targets. Negative binomial and logistic regression models were used to examine the association between school absence and type of respiratory viruses; endpoints included mean days absent from school and prolonged (>2 days) absence. We examined the association between influenza vaccination and school absence among children with RT‐PCR‐confirmed influenza. RESULTS: Among 1027 children, 2295 days of school were missed due to medically attended ARIs; influenza accounted for 39% of illness episodes and 47% of days missed. Mean days absent were highest for influenza (0.96‐1.19) and lowest for coronavirus (0.62). Children with B/Yamagata infection were more likely to report prolonged absence than children with A/H1N1 or A/H3N2 infection [OR (95% CI): 2.1 (1.0, 4.5) and 1.7 (1.0, 2.9), respectively]. Among children with influenza, vaccination status was not associated with prolonged absence. CONCLUSIONS: School absenteeism due to medically attended ARIs varies by viral infection. Influenza B infections accounted for the greatest burden of absenteeism.",2017 May 15,"['McLean, Huong Q.', 'Peterson, Siri H.', 'King, Jennifer P.', 'Meece, Jennifer K.', 'Belongia, Edward A.']",Influenza Other Respir Viruses,,,True
6653fce31fb0a8080aa11dde06f1c32032b28950,PMC,Studying Lactoferrin N-Glycosylation,http://dx.doi.org/10.3390/ijms18040870,PMC5412451,28425960,CC BY,"Lactoferrin is a multifunctional glycoprotein found in the milk of most mammals. In addition to its well-known role of binding iron, lactoferrin carries many important biological functions, including the promotion of cell proliferation and differentiation, and as an anti-bacterial, anti-viral, and anti-parasitic protein. These functions differ among lactoferrin homologs in mammals. Although considerable attention has been given to the many functions of lactoferrin, its primary nutritional contribution is presumed to be related to its iron-binding characteristics, whereas the role of glycosylation has been neglected. Given the critical role of glycan binding in many biological processes, the glycan moieties in lactoferrin are likely to contribute significantly to the biological roles of lactoferrin. Despite the high amino acid sequence homology in different lactoferrins (up to 99%), each exhibits a unique glycosylation pattern that may be responsible for heterogeneity of the biological properties of lactoferrins. An important task for the production of biotherapeutics and medical foods containing bioactive glycoproteins is the assessment of the contributions of individual glycans to the observed bioactivities. This review examines how the study of lactoferrin glycosylation patterns can increase our understanding of lactoferrin functionality.",2017 Apr 20,"['Karav, Sercan', 'German, J. Bruce', 'Rouquié, Camille', 'Le Parc, Annabelle', 'Barile, Daniela']",Int J Mol Sci,,,True
7455510a39b00af17f318760b7da8b37cc336476,PMC,"Stable Internal Reference Genes for Normalizing Real-Time Quantitative PCR in Baphicacanthus cusia under Hormonal Stimuli and UV Irradiation, and in Different Plant Organs",http://dx.doi.org/10.3389/fpls.2017.00668,PMC5413499,28515733,CC BY,"Baphicacanthus cusia (Nees) Bremek, the plant source for many kinds of drugs in traditional Chinese medicine, is widely distributed in South China, especially in Fujian. Recent studies about B. cusia mainly focus on its chemical composition and pharmacological effects, but further analysis of the plant's gene functions and expression is required to better understand the synthesis of its effective compounds. Real-time quantitative polymerase chain reaction (RT-qPCR) is a powerful method for gene expression analysis. It is necessary to select a suitable reference gene for expression normalization to ensure the accuracy of RT-qPCR results. Ten candidate reference genes were selected from the transcriptome datasets of B. cusia in this study, and the expression stability was assessed across 60 samples representing different tissues and organs under various conditions, including ultraviolet (UV) irradiation, hormonal stimuli (jasmonic acid methyl ester and abscisic acid), and in different plant organs. By employing different algorithms, such as geNorm, NormFinder, and BestKeeper, which are complementary approaches based on different statistical procedures, 18S rRNA was found to be the most stable gene under UV irradiation and hormonal stimuli, whereas ubiquitin-conjugating enzyme E2 was the best suitable gene for different plant organs. This novel study aimed to screen for suitable reference genes and corresponding primer pairs specifically designed for gene expression studies in B. cusia, in particular for RT-qPCR analyses.",2017 May 3,"['Huang, Yuxiang', 'Tan, Hexin', 'Yu, Jian', 'Chen, Yue', 'Guo, Zhiying', 'Wang, Guoquan', 'Zhang, Qinglei', 'Chen, Junfeng', 'Zhang, Lei', 'Diao, Yong']",Front Plant Sci,,,True
eabfb15b60476742917f92c6fb60a7bc6ec203aa,PMC,miR-142-5p Disrupts Neuronal Morphogenesis Underlying Porcine Hemagglutinating Encephalomyelitis Virus Infection by Targeting Ulk1,http://dx.doi.org/10.3389/fcimb.2017.00155,PMC5413507,28516065,CC BY,"Porcine hemagglutinating encephalomyelitis virus (PHEV) invades the central nervous system (CNS) and causes neurodegenerative disease in suckling piglets, but the understanding of its neuropathogenicity for neurological dysfunction remains limited. Here, we report that miR-142-5p is localized to neurons and negatively regulates neuronal morphogenesis in porcine hemagglutinating encephalomyelitis (PHE). This phenotype was mediated by miR-142-5p inhibition of an mRNA encoding unc-51-like-kinase1 (Ulk1), which controls axon outgrowth and dendrite formation. Modulating miR-142-5p activity by microRNA mimics or inhibitors induced neurodegeneration, including stunted axon elongation, unstable dendritic spine formation, and irregular swelling and disconnection in neurites. Relieving Ulk1 mRNA repression in primary cortical neurons by miR-142-5p antagomirs or replication-deficient adenoviruses encoding Ulk1 (Ad5-Ulk1), which improved rescue of nerve injury, restricted viral replication, and increased survival rate in mice underlying PHEV infection. In contrast, disrupting Ulk1 in RNAi-expressing neurons mostly led to significantly shortened axon elongation and/or an abnormally large number of branched dendrites. Taken together, we demonstrated that the abnormal neuronal morphogenesis underlying PHEV infection was mainly caused by functional mRNA repression of the miR-142-5p target Ulk1. Our data revealed that PHEV adapted to use spatiotemporal control of host microRNAs to invade CNS, and provided new insights into the virus-associated neurological dysfunction microenvironment.",2017 May 3,"['Li, Zi', 'Lan, Yungang', 'Zhao, Kui', 'Lv, Xiaoling', 'Ding, Ning', 'Lu, Huijun', 'Zhang, Jing', 'Yue, Huiqing', 'Shi, Junchao', 'Song, Deguang', 'Gao, Feng', 'He, Wenqi']",Front Cell Infect Microbiol,,,True
1e6a2c4a8b53fccd969c59445d25c7047d1b1cca,PMC,Structural and functional analysis of Oceanobacillus iheyensis macrodomain reveals a network of waters involved in substrate binding and catalysis,http://dx.doi.org/10.1098/rsob.160327,PMC5413906,28446708,CC BY,"Macrodomains are ubiquitous conserved domains that bind or transform ADP-ribose (ADPr) metabolites. In humans, they are involved in transcription, X-chromosome inactivation, neurodegeneration and modulating PARP1 signalling, making them potential targets for therapeutic agents. Unfortunately, some aspects related to the substrate binding and catalysis of MacroD-like macrodomains still remain unclear, since mutation of the proposed catalytic aspartate does not completely abolish enzyme activity. Here, we present a functional and structural characterization of a macrodomain from the extremely halotolerant and alkaliphilic bacterium Oceanobacillus iheyensis (OiMacroD), related to hMacroD1/hMacroD2, shedding light on substrate binding and catalysis. The crystal structures of D40A, N30A and G37V mutants, and those with MES, ADPr and ADP bound, allowed us to identify five fixed water molecules that play a significant role in substrate binding. Closure of the β6–α4 loop is revealed as essential not only for pyrophosphate recognition, but also for distal ribose orientation. In addition, a novel structural role for residue D40 is identified. Furthermore, it is revealed that OiMacroD not only catalyses the hydrolysis of O-acetyl-ADP-ribose but also reverses protein mono-ADP-ribosylation. Finally, mutant G37V supports the participation of a substrate-coordinated water molecule in catalysis that helps to select the proper substrate conformation.",2017 Apr 26,"['Zapata-Pérez, Rubén', 'Gil-Ortiz, Fernando', 'Martínez-Moñino, Ana Belén', 'García-Saura, Antonio Ginés', 'Juanhuix, Jordi', 'Sánchez-Ferrer, Álvaro']",Open Biol,,,False
a49923d05f7decbdc6f0d8a3825fd2cfb6711775,PMC,Structural and functional analysis of Oceanobacillus iheyensis macrodomain reveals a network of waters involved in substrate binding and catalysis,http://dx.doi.org/10.1098/rsob.160327,PMC5413906,28446708,CC BY,"Macrodomains are ubiquitous conserved domains that bind or transform ADP-ribose (ADPr) metabolites. In humans, they are involved in transcription, X-chromosome inactivation, neurodegeneration and modulating PARP1 signalling, making them potential targets for therapeutic agents. Unfortunately, some aspects related to the substrate binding and catalysis of MacroD-like macrodomains still remain unclear, since mutation of the proposed catalytic aspartate does not completely abolish enzyme activity. Here, we present a functional and structural characterization of a macrodomain from the extremely halotolerant and alkaliphilic bacterium Oceanobacillus iheyensis (OiMacroD), related to hMacroD1/hMacroD2, shedding light on substrate binding and catalysis. The crystal structures of D40A, N30A and G37V mutants, and those with MES, ADPr and ADP bound, allowed us to identify five fixed water molecules that play a significant role in substrate binding. Closure of the β6–α4 loop is revealed as essential not only for pyrophosphate recognition, but also for distal ribose orientation. In addition, a novel structural role for residue D40 is identified. Furthermore, it is revealed that OiMacroD not only catalyses the hydrolysis of O-acetyl-ADP-ribose but also reverses protein mono-ADP-ribosylation. Finally, mutant G37V supports the participation of a substrate-coordinated water molecule in catalysis that helps to select the proper substrate conformation.",2017 Apr 26,"['Zapata-Pérez, Rubén', 'Gil-Ortiz, Fernando', 'Martínez-Moñino, Ana Belén', 'García-Saura, Antonio Ginés', 'Juanhuix, Jordi', 'Sánchez-Ferrer, Álvaro']",Open Biol,,,True
610f76ebccfa38957d15943fab5eb37c13ee6040,PMC,Illumina MiSeq 16S amplicon sequence analysis of bovine respiratory disease associated bacteria in lung and mediastinal lymph node tissue,http://dx.doi.org/10.1186/s12917-017-1035-2,PMC5414144,28464950,CC BY,"BACKGROUND: Bovine respiratory disease (BRD) is caused by growth of single or multiple species of pathogenic bacteria in lung tissue following stress and/or viral infection. Next generation sequencing of 16S ribosomal RNA gene PCR amplicons (NGS 16S amplicon analysis) is a powerful culture-independent open reference method that has recently been used to increase understanding of BRD-associated bacteria in the upper respiratory tract of BRD cattle. However, it has not yet been used to examine the microbiome of the bovine lower respiratory tract. The objective of this study was to use NGS 16S amplicon analysis to identify bacteria in post-mortem lung and lymph node tissue samples harvested from fatal BRD cases and clinically healthy animals. Cranial lobe and corresponding mediastinal lymph node post-mortem tissue samples were collected from calves diagnosed as BRD cases by veterinary laboratory pathologists and from clinically healthy calves. NGS 16S amplicon libraries, targeting the V3-V4 region of the bacterial 16S rRNA gene were prepared and sequenced on an Illumina MiSeq. Quantitative insights into microbial ecology (QIIME) was used to determine operational taxonomic units (OTUs) which corresponded to the 16S rRNA gene sequences. RESULTS: Leptotrichiaceae, Mycoplasma, Pasteurellaceae, and Fusobacterium were the most abundant OTUs identified in the lungs and lymph nodes of the calves which died from BRD. Leptotrichiaceae, Fusobacterium, Mycoplasma, Trueperella and Bacteroides had greater relative abundances in post-mortem lung samples collected from fatal cases of BRD in dairy calves, compared with clinically healthy calves without lung lesions. Leptotrichiaceae, Mycoplasma and Pasteurellaceae showed higher relative abundances in post-mortem lymph node samples collected from fatal cases of BRD in dairy calves, compared with clinically healthy calves without lung lesions. Two Leptotrichiaceae sequence contigs were subsequently assembled from bacterial DNA-enriched shotgun sequences. CONCLUSIONS: The microbiomes of the cranial lung lobe and mediastinal lymph node from calves which died from BRD and from clinically healthy H-F calves have been characterised. Contigs corresponding to the abundant Leptotrichiaceae OTU were sequenced and found not to be identical to any known bacterial genus. This suggests that we have identified a novel bacterial species associated with BRD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-017-1035-2) contains supplementary material, which is available to authorized users.",2017 May 2,"['Johnston, Dayle', 'Earley, Bernadette', 'Cormican, Paul', 'Murray, Gerard', 'Kenny, David Anthony', 'Waters, Sinead Mary', 'McGee, Mark', 'Kelly, Alan Kieran', 'McCabe, Matthew Sean']",BMC Vet Res,,,True
155de81e6f3c3ca342aa733e289b749a5394a26b,PMC,Classification of self-assembling protein nanoparticle architectures for applications in vaccine design,http://dx.doi.org/10.1098/rsos.161092,PMC5414263,28484626,CC BY,"We introduce here a mathematical procedure for the structural classification of a specific class of self-assembling protein nanoparticles (SAPNs) that are used as a platform for repetitive antigen display systems. These SAPNs have distinctive geometries as a consequence of the fact that their peptide building blocks are formed from two linked coiled coils that are designed to assemble into trimeric and pentameric clusters. This allows a mathematical description of particle architectures in terms of bipartite (3,5)-regular graphs. Exploiting the relation with fullerene graphs, we provide a complete atlas of SAPN morphologies. The classification enables a detailed understanding of the spectrum of possible particle geometries that can arise in the self-assembly process. Moreover, it provides a toolkit for a systematic exploitation of SAPNs in bioengineering in the context of vaccine design, predicting the density of B-cell epitopes on the SAPN surface, which is critical for a strong humoral immune response.",2017 Apr 26,"['Indelicato, G.', 'Burkhard, P.', 'Twarock, R.']",R Soc Open Sci,,,True
220af662ae7d8bf92c9abb43a2f3af1cecda1f21,PMC,Classification of self-assembling protein nanoparticle architectures for applications in vaccine design,http://dx.doi.org/10.1098/rsos.161092,PMC5414263,28484626,CC BY,"We introduce here a mathematical procedure for the structural classification of a specific class of self-assembling protein nanoparticles (SAPNs) that are used as a platform for repetitive antigen display systems. These SAPNs have distinctive geometries as a consequence of the fact that their peptide building blocks are formed from two linked coiled coils that are designed to assemble into trimeric and pentameric clusters. This allows a mathematical description of particle architectures in terms of bipartite (3,5)-regular graphs. Exploiting the relation with fullerene graphs, we provide a complete atlas of SAPN morphologies. The classification enables a detailed understanding of the spectrum of possible particle geometries that can arise in the self-assembly process. Moreover, it provides a toolkit for a systematic exploitation of SAPNs in bioengineering in the context of vaccine design, predicting the density of B-cell epitopes on the SAPN surface, which is critical for a strong humoral immune response.",2017 Apr 26,"['Indelicato, G.', 'Burkhard, P.', 'Twarock, R.']",R Soc Open Sci,,,False
cac8f96521f21bbd0a84861a98a5715d86b293f6,PMC,Prevalence of non-influenza respiratory viruses in acute respiratory infection cases in Mexico,http://dx.doi.org/10.1371/journal.pone.0176298,PMC5415110,28467515,CC BY,"BACKGROUND: Acute respiratory infections are the leading cause of morbidity and mortality worldwide. Although a viral aetiological agent is estimated to be involved in up to 80% of cases, the majority of these agents have never been specifically identified. Since 2009, diagnostic and surveillance efforts for influenza virus have been applied worldwide. However, insufficient epidemiological information is available for the many other respiratory viruses that can cause Acute respiratory infections. METHODS: This study evaluated the presence of 14 non-influenza respiratory viruses in 872 pharyngeal exudate samples using RT-qPCR. All samples met the operational definition of a probable case of an influenza-like illness or severe acute respiratory infection and had a previous negative result for influenza by RT-qPCR. RESULTS: The presence of at least one non-influenza virus was observed in 312 samples (35.8%). The most frequent viruses were rhinovirus (RV; 33.0%), human respiratory syncytial virus (HRSV; 30.8%) and human metapneumovirus (HMPV; 10.6%). A total of 56 cases of co-infection (17.9%) caused by 2, 3, or 4 viruses were identified. Approximately 62.5% of all positive cases were in children under 9 years of age. CONCLUSION: In this study, we identified 13 non-influenza respiratory viruses that could occur in any season of the year. This study provides evidence for the prevalence and seasonality of a wide range of respiratory viruses that circulate in Mexico and constitute a risk for the population. Additionally, our data suggest that including these tests more widely in the diagnostic algorithm for influenza may reduce the use of unnecessary antibiotics, reduce the hospitalisation time, and enrich national epidemiological data with respect to the infections caused by these viruses.",2017 May 3,"['Fernandes-Matano, Larissa', 'Monroy-Muñoz, Irma Eloísa', 'Angeles-Martínez, Javier', 'Sarquiz-Martinez, Brenda', 'Palomec-Nava, Iliana Donají', 'Pardavé-Alejandre, Hector Daniel', 'Santos Coy-Arechavaleta, Andrea', 'Santacruz-Tinoco, Clara Esperanza', 'González-Ibarra, Joaquín', 'González-Bonilla, Cesar Raúl', 'Muñoz-Medina, José Esteban']",PLoS One,,,True
502dd3d54b1d6ee5cf901fd441afdf5231cffa2b,PMC,Frequent respiratory viral infections in a young child in a 27-month follow-up study,http://dx.doi.org/10.1099/jmmcr.0.003020,PMC5415931,28663808,CC BY,"INTRODUCTION: Viruses are major aetiological agents of acute respiratory infection in young children. Although many studies have reported detection and analysis of respiratory viruses in sporadic cases, there have been few follow-up studies of individuals. The purpose of this study was to investigate the frequency of respiratory viral infections in a young child and to examine the duration of viral genome detection in clinical specimens. CASE PRESENTATION: A total of 284 nasal swabs were collected during symptomatic (196 specimens) and asymptomatic (88 specimens) periods of respiratory symptoms from a young female child (from 4 months to 31 months of age, who was admitted to a nursery school at 9 months). Multiplex real-time PCR for 19 respiratory viruses or subtypes was performed. One hundred and ninety-eight of the tested specimens were virus positive (69.7 %) (symptomatic periods, 149/196, 76.0 %; asymptomatic periods, 49/88, 55.7 %). Rhinovirus was the most frequently detected (26 times). Long durations of detection were observed for human coronavirus NL63 (30 days), rhinovirus (28 days) and human bocavirus 1 (22 days). CONCLUSION: Young children living in a group context have a high risk of respiratory virus infections, especially rhinovirus. In some instances, viral genomes were detectable for about 1 month by PCR.",2014 Dec 1,"['Kaida, Atsushi', 'Kubo, Hideyuki', 'Iritani, Nobuhiro', 'Yamamoto, Seiji P', 'Hase, Atsushi', 'Takakura, Koh-Ichi', 'Kageyema, Tsutomu']",JMM Case Rep,,,True
4e81510515bcfe6d1c087b341e34e9b0331a0c3a,PMC,"InfectiousDiseases ofPoverty, the first five years",http://dx.doi.org/10.1186/s40249-017-0310-6,PMC5415955,28472981,CC BY,"Although the focus in the area of health research may be shifting from infectious to non-communicable diseases, the infectious diseases of poverty remain a major burden of disease of global health concern. A global platform to communicate and share the research on these diseases is needed to facilitate the translation of knowledge into effective approaches and tools for their elimination. Based on the “One health, One world” mission, a new, open-access journal, Infectious Diseases of Poverty (IDP), was launched by BioMed Central in partnership with the National Institute of Parasitic Diseases (NIPD), Chinese Center for Disease Control and Prevention (China CDC) on October 25, 2012. Its aim is to identify and assess research and information gaps that hinder progress towards new interventions for a particular public health problem in the developing world. From the inaugural IDP issue of October 25, 2012, a total of 256 manuscripts have been published over the following five years. Apart from a small number of editorials, opinions, commentaries and letters to the editor, the predominant types of publications are research articles (69.5%) and scoping reviews (21.5%). A total of 1 081 contributing authors divided between 323 affiliations across 68 countries, territories and regions produced these 256 publications. The journal is indexed in major international biomedical databases, including Web of Science, PubMed, Scopus and Embase. In 2015, it was assigned its first impact factor (4.11), which is now 2.13. During the past five years, IDP has received manuscripts from 90 countries, territories and regions across six continents with an annual acceptance rate of all contributions maintained at less than 40%. Content analysis shows that neglected tropical diseases (NTDs), followed by the “Big Three” (HIV/AIDS, malaria and tuberculosis) and infectious diseases in general comprise 88% of all publications. In addition, a series of 10 thematic issues, covering 118 publications in all, was published as separate parts of the first five volumes. These publications were cited 975 times, which equals an average of 8.3 times per publication. The current challenge is to identify cutting-edge research topics and attract and to publish first-rate publications leading to increasing importance and impact of the journal in its field. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-017-0310-6) contains supplementary material, which is available to authorized users.",2017 May 4,"['Wang, Wei', 'Chen, Jin', 'Sheng, Hui-Feng', 'Wang, Na-Na', 'Yang, Pin', 'Zhou, Xiao-Nong', 'Bergquist, Robert']",Infect Dis Poverty,,,False
c7bbdf2417a1b37fd9c1886c186e7a1b6fedc6ea,PMC,"InfectiousDiseases ofPoverty, the first five years",http://dx.doi.org/10.1186/s40249-017-0310-6,PMC5415955,28472981,CC BY,"Although the focus in the area of health research may be shifting from infectious to non-communicable diseases, the infectious diseases of poverty remain a major burden of disease of global health concern. A global platform to communicate and share the research on these diseases is needed to facilitate the translation of knowledge into effective approaches and tools for their elimination. Based on the “One health, One world” mission, a new, open-access journal, Infectious Diseases of Poverty (IDP), was launched by BioMed Central in partnership with the National Institute of Parasitic Diseases (NIPD), Chinese Center for Disease Control and Prevention (China CDC) on October 25, 2012. Its aim is to identify and assess research and information gaps that hinder progress towards new interventions for a particular public health problem in the developing world. From the inaugural IDP issue of October 25, 2012, a total of 256 manuscripts have been published over the following five years. Apart from a small number of editorials, opinions, commentaries and letters to the editor, the predominant types of publications are research articles (69.5%) and scoping reviews (21.5%). A total of 1 081 contributing authors divided between 323 affiliations across 68 countries, territories and regions produced these 256 publications. The journal is indexed in major international biomedical databases, including Web of Science, PubMed, Scopus and Embase. In 2015, it was assigned its first impact factor (4.11), which is now 2.13. During the past five years, IDP has received manuscripts from 90 countries, territories and regions across six continents with an annual acceptance rate of all contributions maintained at less than 40%. Content analysis shows that neglected tropical diseases (NTDs), followed by the “Big Three” (HIV/AIDS, malaria and tuberculosis) and infectious diseases in general comprise 88% of all publications. In addition, a series of 10 thematic issues, covering 118 publications in all, was published as separate parts of the first five volumes. These publications were cited 975 times, which equals an average of 8.3 times per publication. The current challenge is to identify cutting-edge research topics and attract and to publish first-rate publications leading to increasing importance and impact of the journal in its field. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-017-0310-6) contains supplementary material, which is available to authorized users.",2017 May 4,"['Wang, Wei', 'Chen, Jin', 'Sheng, Hui-Feng', 'Wang, Na-Na', 'Yang, Pin', 'Zhou, Xiao-Nong', 'Bergquist, Robert']",Infect Dis Poverty,,,True
61843499666ad3d4f0ea75554cd06a745e9a7f8e,PMC,Different evolutionary trajectories of vaccine-controlled and non-controlled avian infectious bronchitis viruses in commercial poultry,http://dx.doi.org/10.1371/journal.pone.0176709,PMC5417570,28472110,CC0,"To determine the genetic and epidemiological relationship of infectious bronchitis virus (IBV) isolates from commercial poultry to attenuated live IBV vaccines we conducted a phylogenetic network analysis on the full-length S1 sequence for Arkansas (Ark), Massachusetts (Mass) and Delmarva/1639 (DMV/1639) type viruses isolated in 2015 from clinical cases by 3 different diagnostic laboratories. Phylogenetic network analysis of Ark isolates showed two predominant groups linked by 2 mutations, consistent with subpopulations found in commercial vaccines for this IBV type. In addition, a number of satellite groups surrounding the two predominant populations were observed for the Ark type virus, which is likely due to mutations associated with the nature of this vaccine to persist in flocks. The phylogenetic network analysis of Mass-type viruses shows two groupings corresponding to different manufacturers vaccine sequences. No satellite groups were observed for Mass-type viruses, which is consistent with no persistence of this vaccine type in the field. At the time of collection, no vaccine was being used for the DMV/1639 type viruses and phylogenetic network analysis showed a dispersed network suggesting no clear change in genetic distribution. Selection pressure analysis showed that the DMV/1639 and Mass-type strains were evolving under negative selection, whereas the Ark type viruses had evolved under positive selection. This data supports the hypothesis that live attenuated vaccine usage does play a role in the genetic profile of similar IB viruses in the field and phylogenetic network analysis can be used to identify vaccine and vaccine origin isolates, which is important for our understanding of the role live vaccines play in the evolutionary trajectory of those viruses.",2017 May 4,"['Jackwood, Mark W.', 'Lee, Dong-Hun']",PLoS One,,,True
90f2e2a33f7f6bae27a703b4c30a99f87d404474,PMC,"The comparative immunology of wild and laboratory mice, Mus musculus domesticus",http://dx.doi.org/10.1038/ncomms14811,PMC5418598,28466840,CC BY,"The laboratory mouse is the workhorse of immunology, used as a model of mammalian immune function, but how well immune responses of laboratory mice reflect those of free-living animals is unknown. Here we comprehensively characterize serological, cellular and functional immune parameters of wild mice and compare them with laboratory mice, finding that wild mouse cellular immune systems are, comparatively, in a highly activated (primed) state. Associations between immune parameters and infection suggest that high level pathogen exposure drives this activation. Moreover, wild mice have a population of highly activated myeloid cells not present in laboratory mice. By contrast, in vitro cytokine responses to pathogen-associated ligands are generally lower in cells from wild mice, probably reflecting the importance of maintaining immune homeostasis in the face of intense antigenic challenge in the wild. These data provide a comprehensive basis for validating (or not) laboratory mice as a useful and relevant immunological model system.",2017 May 3,"['Abolins, Stephen', 'King, Elizabeth C.', 'Lazarou, Luke', 'Weldon, Laura', 'Hughes, Louise', 'Drescher, Paul', 'Raynes, John G.', 'Hafalla, Julius C. R.', 'Viney, Mark E.', 'Riley, Eleanor M.']",Nat Commun,,,True
f23dfb23efee3476cb3f07e1e2606d2788ef7c02,PMC,"The comparative immunology of wild and laboratory mice, Mus musculus domesticus",http://dx.doi.org/10.1038/ncomms14811,PMC5418598,28466840,CC BY,"The laboratory mouse is the workhorse of immunology, used as a model of mammalian immune function, but how well immune responses of laboratory mice reflect those of free-living animals is unknown. Here we comprehensively characterize serological, cellular and functional immune parameters of wild mice and compare them with laboratory mice, finding that wild mouse cellular immune systems are, comparatively, in a highly activated (primed) state. Associations between immune parameters and infection suggest that high level pathogen exposure drives this activation. Moreover, wild mice have a population of highly activated myeloid cells not present in laboratory mice. By contrast, in vitro cytokine responses to pathogen-associated ligands are generally lower in cells from wild mice, probably reflecting the importance of maintaining immune homeostasis in the face of intense antigenic challenge in the wild. These data provide a comprehensive basis for validating (or not) laboratory mice as a useful and relevant immunological model system.",2017 May 3,"['Abolins, Stephen', 'King, Elizabeth C.', 'Lazarou, Luke', 'Weldon, Laura', 'Hughes, Louise', 'Drescher, Paul', 'Raynes, John G.', 'Hafalla, Julius C. R.', 'Viney, Mark E.', 'Riley, Eleanor M.']",Nat Commun,,,True
bf2b703218a69722979c495a0898ddff3d7d998d,PMC,Rhinovirus C targets ciliated airway epithelial cells,http://dx.doi.org/10.1186/s12931-017-0567-0,PMC5418766,28472984,CC BY,"BACKGROUND: The Rhinovirus C (RV-C), first identified in 2006, produce high symptom burdens in children and asthmatics, however, their primary target host cell in the airways remains unknown. Our primary hypotheses were that RV-C target ciliated airway epithelial cells (AECs), and that cell specificity is determined by restricted and high expression of the only known RV-C cell-entry factor, cadherin related family member 3 (CDHR3). METHODS: RV-C15 (C15) infection in differentiated human bronchial epithelial cell (HBEC) cultures was assessed using immunofluorescent and time-lapse epifluorescent imaging. Morphology of C15-infected differentiated AECs was assessed by immunohistochemistry. RESULTS: C15 produced a scattered pattern of infection, and infected cells were shed from the epithelium. The percentage of cells infected with C15 varied from 1.4 to 14.7% depending on cell culture conditions. Infected cells had increased staining for markers of ciliated cells (acetylated-alpha-tubulin [aat], p < 0.001) but not markers of goblet cells (wheat germ agglutinin or Muc5AC, p = ns). CDHR3 expression was increased on ciliated epithelial cells, but not other epithelial cells (p < 0.01). C15 infection caused a 27.4% reduction of ciliated cells expressing CDHR3 (p < 0.01). During differentiation of AECs, CDHR3 expression progressively increased and correlated with both RV-C binding and replication. CONCLUSIONS: The RV-C only replicate in ciliated AECs in vitro, leading to infected cell shedding. CDHR3 expression positively correlates with RV-C binding and replication, and is largely confined to ciliated AECs. Our data imply that factors regulating differentiation and CDHR3 production may be important determinants of RV-C illness severity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-017-0567-0) contains supplementary material, which is available to authorized users.",2017 May 4,"['Griggs, Theodor F.', 'Bochkov, Yury A.', 'Basnet, Sarmila', 'Pasic, Thomas R.', 'Brockman-Schneider, Rebecca A.', 'Palmenberg, Ann C.', 'Gern, James E.']",Respir Res,,,False
625c0fb8bd8fe9121b9139f318397b074208d5e4,PMC,Rhinovirus C targets ciliated airway epithelial cells,http://dx.doi.org/10.1186/s12931-017-0567-0,PMC5418766,28472984,CC BY,"BACKGROUND: The Rhinovirus C (RV-C), first identified in 2006, produce high symptom burdens in children and asthmatics, however, their primary target host cell in the airways remains unknown. Our primary hypotheses were that RV-C target ciliated airway epithelial cells (AECs), and that cell specificity is determined by restricted and high expression of the only known RV-C cell-entry factor, cadherin related family member 3 (CDHR3). METHODS: RV-C15 (C15) infection in differentiated human bronchial epithelial cell (HBEC) cultures was assessed using immunofluorescent and time-lapse epifluorescent imaging. Morphology of C15-infected differentiated AECs was assessed by immunohistochemistry. RESULTS: C15 produced a scattered pattern of infection, and infected cells were shed from the epithelium. The percentage of cells infected with C15 varied from 1.4 to 14.7% depending on cell culture conditions. Infected cells had increased staining for markers of ciliated cells (acetylated-alpha-tubulin [aat], p < 0.001) but not markers of goblet cells (wheat germ agglutinin or Muc5AC, p = ns). CDHR3 expression was increased on ciliated epithelial cells, but not other epithelial cells (p < 0.01). C15 infection caused a 27.4% reduction of ciliated cells expressing CDHR3 (p < 0.01). During differentiation of AECs, CDHR3 expression progressively increased and correlated with both RV-C binding and replication. CONCLUSIONS: The RV-C only replicate in ciliated AECs in vitro, leading to infected cell shedding. CDHR3 expression positively correlates with RV-C binding and replication, and is largely confined to ciliated AECs. Our data imply that factors regulating differentiation and CDHR3 production may be important determinants of RV-C illness severity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-017-0567-0) contains supplementary material, which is available to authorized users.",2017 May 4,"['Griggs, Theodor F.', 'Bochkov, Yury A.', 'Basnet, Sarmila', 'Pasic, Thomas R.', 'Brockman-Schneider, Rebecca A.', 'Palmenberg, Ann C.', 'Gern, James E.']",Respir Res,,,True
93507716d80b9834a1ee584b038c1be54c0790a8,PMC,Proteomic Analysis of Chicken Skeletal Muscle during Embryonic Development,http://dx.doi.org/10.3389/fphys.2017.00281,PMC5420592,28533755,CC BY,"Embryonic growth and development of skeletal muscle is a major determinant of muscle mass, and has a significant effect on meat production in chicken. To assess the protein expression profiles during embryonic skeletal muscle development, we performed a proteomics analysis using isobaric tags for relative and absolute quantification (iTRAQ) in leg muscle tissues of female Xinghua chicken at embryonic age (E) 11, E16, and 1-day post hatch (D1). We identified 3,240 proteins in chicken embryonic muscle and 491 of them were differentially expressed (fold change ≥ 1.5 or ≤ 0.666 and p < 0.05). There were 19 up- and 32 down-regulated proteins in E11 vs. E16 group, 238 up- and 227 down-regulated proteins in E11 vs. D1 group, and 13 up- and 5 down-regulated proteins in E16 vs. D1 group. Protein interaction network analyses indicated that these differentially expressed proteins were mainly involved in the pathway of protein synthesis, muscle contraction, and oxidative phosphorylation. Integrative analysis of proteome and our previous transcriptome data found 189 differentially expressed proteins that correlated with their mRNA level. The interactions between these proteins were also involved in muscle contraction and oxidative phosphorylation pathways. The lncRNA-protein interaction network found four proteins DMD, MYL3, TNNI2, and TNNT3 that are all involved in muscle contraction and may be lncRNA regulated. These results provide several candidate genes for further investigation into the molecular mechanisms of chicken embryonic muscle development, and enable us to better understanding their regulation networks and biochemical pathways.",2017 May 8,"['Ouyang, Hongjia', 'Wang, Zhijun', 'Chen, Xiaolan', 'Yu, Jiao', 'Li, Zhenhui', 'Nie, Qinghua']",Front Physiol,,,True
5ba627a0ae4eae9a35185493fbfb080849d1ce5e,PMC,"The discovery of a novel compound with potent antitumor activity: virtual screening, synthesis, biological evaluation and preliminary mechanism study",http://dx.doi.org/10.18632/oncotarget.15601,PMC5421875,28445950,CC BY,"Farnesyltransferase has been regarded as a promising drug target against cancer as it is critical for membrane association of several signal transduction proteins. In this study, a novel farnesyltransferase inhibitor (IMB-1406) was identified through virtual screening. It exhibits stronger potency (IC(50)s: 6.92–8.99 μM) than Sunitinib against all of the tested cancer cell lines. Preliminary studies on mechanism reveal that IMB-1406 induces apoptosis in HepG2 cells by arresting the cell cycle at the S phase, altering anti- and pro-apoptotic proteins leading to mitochondrial dysfunction and activation of caspase-3. This anti-tumor effect is most probably related to the inhibition of farnesyltransferase as indicated by molecular docking. Overall, IMB-1406 is a novel lead compound with potent antitumor activity and deserves further structural modifications.",2017 Feb 21,"['Jin, Yuanyuan', 'Li, Linhu', 'Yang, Zhaoyong', 'Liu, Mingliang', 'Guo, Huiyuan', 'Shen, Weiyi']",Oncotarget,,,True
5a1a67485f8d803e18aeb66383d616ceac659b47,PMC,Global miRNA expression profiling of domestic cat livers following acute Toxoplasma gondii infection,http://dx.doi.org/10.18632/oncotarget.16108,PMC5421954,28424428,CC BY,"Although microRNAs (miRNAs) play an important role in liver homeostasis, the extent to which they can be altered by Toxoplasma gondii infection is unknown. Here, we utilized small RNA sequencing and bioinformatic analyses to characterize miRNA expression profiles in the liver of domestic cats at 7 days after oral infection with T. gondii (Type II) strain. A total of 384 miRNAs were identified and 82 were differentially expressed, of which 33 were up-regulated and 49 down-regulated. Also, 5690 predicted host gene targets for the differentially expressed miRNAs were identified using the bioinformatic algorithm miRanda. Gene ontology analysis revealed that the predicted gene targets of the dysregulated miRNAs were significantly enriched in apoptosis. Kyoto Encyclopedia of Genes and Genomes analysis showed that the predicted gene targets were involved in several pathways, including acute myeloid leukemia, central carbon metabolism in cancer, choline metabolism in cancer, estrogen signaling pathway, fatty acid degradation, lysosome, nucleotide excision repair, progesterone-mediated oocyte maturation, and VEGF signaling pathway. The expression level of 6 upregulated miRNAs (mmu-miR-21a-5p, mmu-miR-20a-5p, mmu-miR-17-5p, mmu-miR-30e-3p, mmu-miR-142a-3p, and mmu-miR-106b-3p) was confirmed by stem-loop quantitative reverse transcription PCR, which yielded results consistent with the sequencing data. These findings expand our understanding of the regulatory mechanisms of miRNAs underlying T. gondii pathogenesis and contribute new database information on cat miRNAs, opening a new perspective on the prevention and treatment of T. gondii infection.",2017 Mar 10,"['Cong, Wei', 'Zhang, Xiao-Xuan', 'He, Jun-Jun', 'Li, Fa-Cai', 'Elsheikha, Hany M.', 'Zhu, Xing-Quan']",Oncotarget,,,True
2ed8fab215c4a6bccfd5c69af99a77c6d0233be1,PMC,Global miRNA expression profiling of domestic cat livers following acute Toxoplasma gondii infection,http://dx.doi.org/10.18632/oncotarget.16108,PMC5421954,28424428,CC BY,"Although microRNAs (miRNAs) play an important role in liver homeostasis, the extent to which they can be altered by Toxoplasma gondii infection is unknown. Here, we utilized small RNA sequencing and bioinformatic analyses to characterize miRNA expression profiles in the liver of domestic cats at 7 days after oral infection with T. gondii (Type II) strain. A total of 384 miRNAs were identified and 82 were differentially expressed, of which 33 were up-regulated and 49 down-regulated. Also, 5690 predicted host gene targets for the differentially expressed miRNAs were identified using the bioinformatic algorithm miRanda. Gene ontology analysis revealed that the predicted gene targets of the dysregulated miRNAs were significantly enriched in apoptosis. Kyoto Encyclopedia of Genes and Genomes analysis showed that the predicted gene targets were involved in several pathways, including acute myeloid leukemia, central carbon metabolism in cancer, choline metabolism in cancer, estrogen signaling pathway, fatty acid degradation, lysosome, nucleotide excision repair, progesterone-mediated oocyte maturation, and VEGF signaling pathway. The expression level of 6 upregulated miRNAs (mmu-miR-21a-5p, mmu-miR-20a-5p, mmu-miR-17-5p, mmu-miR-30e-3p, mmu-miR-142a-3p, and mmu-miR-106b-3p) was confirmed by stem-loop quantitative reverse transcription PCR, which yielded results consistent with the sequencing data. These findings expand our understanding of the regulatory mechanisms of miRNAs underlying T. gondii pathogenesis and contribute new database information on cat miRNAs, opening a new perspective on the prevention and treatment of T. gondii infection.",2017 Mar 10,"['Cong, Wei', 'Zhang, Xiao-Xuan', 'He, Jun-Jun', 'Li, Fa-Cai', 'Elsheikha, Hany M.', 'Zhu, Xing-Quan']",Oncotarget,,,False
3115260ab0b83020627a59f8e6c47d8e33337d3d,PMC,Comparing national infectious disease surveillance systems: China and the Netherlands,http://dx.doi.org/10.1186/s12889-017-4319-3,PMC5423001,28482830,CC BY,"BACKGROUND: Risk assessment and early warning (RAEW) are essential components of any infectious disease surveillance system. In light of the International Health Regulations (IHR)(2005), this study compares the organisation of RAEW in China and the Netherlands. The respective approaches towards surveillance of arboviral disease and unexplained pneumonia were analysed to gain a better understanding of the RAEW mode of operation. This study may be used to explore options for further strengthening of global collaboration and timely detection and surveillance of infectious disease outbreaks. METHODS: A qualitative study design was used, combining data retrieved from the literature and from semi-structured interviews with Chinese (5 national-level and 6 provincial-level) and Dutch (5 national-level) experts. RESULTS: The results show that some differences exist such as in the use of automated electronic components of the early warning system in China (‘CIDARS’), compared to a more limited automated component in the Netherlands (‘barometer’). Moreover, RAEW units in the Netherlands focus exclusively on infectious diseases, while China has a broader ‘all hazard’ approach (including for example chemical incidents). In the Netherlands, veterinary specialists take part at the RAEW meetings, to enable a structured exchange/assessment of zoonotic signals. CONCLUSION: Despite these differences, the main conclusion is that for the two infections studied, the early warning system in China and the Netherlands are remarkably similar considering their large differences in infectious disease history, population size and geographical setting. Our main recommendations are continued emphasis on international corporation that requires insight into national infectious disease surveillance systems, the usage of a One Health approach in infectious disease surveillance, and further exploration/strengthening of a combined syndromic and laboratory surveillance system.",2017 May 8,"['Vlieg, Willemijn L.', 'Fanoy, Ewout B.', 'van Asten, Liselotte', 'Liu, Xiaobo', 'Yang, Jun', 'Pilot, Eva', 'Bijkerk, Paul', 'van der Hoek, Wim', 'Krafft, Thomas', 'van der Sande, Marianne A.', 'Liu, Qi-Yong']",BMC Public Health,,,True
b6deb91c6796184b969f10b262910634eeff4a33,PMC,Tumor Restrictions to Oncolytic Virus,http://dx.doi.org/10.3390/biomedicines2020163,PMC5423468,28548066,CC BY,"Oncolytic virotherapy has advanced since the days of its conception but therapeutic efficacy in the clinics does not seem to reach the same level as in animal models. One reason is premature oncolytic virus clearance in humans, which is a reasonable assumption considering the immune-stimulating nature of the oncolytic agents. However, several studies are beginning to reveal layers of restriction to oncolytic virotherapy that are present before an adaptive neutralizing immune response. Some of these barriers are present constitutively halting infection before it even begins, whereas others are raised by minute cues triggered by virus infection. Indeed, we and others have noticed that delivering viruses to tumors may not be the biggest obstacle to successful therapy, but instead the physical make-up of the tumor and its capacity to mount antiviral defenses seem to be the most important efficacy determinants. In this review, we summarize the constitutive and innate barriers to oncolytic virotherapy and discuss strategies to overcome them.",2014 Apr 17,"['Vähä-Koskela, Markus', 'Hinkkanen, Ari']",Biomedicines,,,True
600daeb2ed49a45c29ca225659768556fcee30d3,PMC,Evaluation of Two Dry Commercial Therapeutic Diets for the Management of Feline Chronic Gastroenteropathy,http://dx.doi.org/10.3389/fvets.2017.00069,PMC5423899,28540291,CC BY,"Management of feline chronic gastroenteropathies has included intervention with both veterinary therapeutic formulas designed to manage non-specific gastrointestinal disorders and those designed with limited novel or hydrolyzed ingredients for management of food-responsive enteropathies and steroid-responsive enteropathies (inflammatory bowel disease). There have been few studies evaluating the use of dietary intervention for the management of feline chronic gastroenteropathy. This prospective, multi-center study evaluated the use of two commercially available feline veterinary therapeutic dry diets designed to manage non-specific gastrointestinal disorders in 28 cats with a history of chronic vomiting and/or diarrhea. The majority of cats enrolled in the study had a history of vomiting (n = 25), with a smaller number having a history of concurrent diarrhea (n = 2) or diarrhea alone (n = 3). Cats were excluded if diagnostic tests identified any systemic or infectious disease that could be associated with the clinical signs of vomiting or diarrhea, and if they were panhypoproteinemic, hypoalbuminemic, hypocobalaminemic, or had a Spec fPL ≥5.4 µg/L. Cats were randomized to one of two veterinary therapeutic diets for 4 weeks. Feeding of both therapeutic diets resulted in a numeric reduction in the number of vomiting episodes over the 4-week period, but no significant differences were seen between dietary interventions. When looking within dietary groups, significant differences were seen in cats fed Diet A with reductions of 69.1, 73.3, and 63.2% (p values of 0.008, 0.003, and 0.029) in weeks 2, 3, and 4, respectively, when compared to week 0. The probability of vomiting also showed significant reductions in cats fed Diet A between weeks 0 and 2, 3, and 4, with odds ratios of 0.008, 0.005, and 0.005, respectively (p values of 0.038, 0.23, and 0.23). Results of this study demonstrate that a veterinary therapeutic gastrointestinal formula can be effective in the management of feline chronic vomiting. Cats that fail to respond to this dietary approach after a 2- to 4-week trial may benefit from a limited novel or hydrolyzed ingredient formula and may require additional diagnostics to better characterize the underlying disease.",2017 May 10,"['Perea, Sally C.', 'Marks, Stanley L.', 'Daristotle, Leighann', 'Koochaki, Patricia E.', 'Haydock, Richard']",Front Vet Sci,,,True
c9b696a38ac25d3289283045ac72c8af370dda7a,PMC,Novel Mechanisms Revealed in the Trachea Transcriptome of Resistant and Susceptible Chicken Lines following Infection with Newcastle Disease Virus,http://dx.doi.org/10.1128/CVI.00027-17,PMC5424241,28331077,CC BY,"Newcastle disease virus (NDV) has a devastating impact on poultry production in developing countries. This study examined the transcriptome of tracheal epithelial cells from two inbred chicken lines that differ in NDV susceptibility after challenge with a high-titer inoculum of lentogenic NDV. The Fayoumi line had a significantly lower NDV load postchallenge than the Leghorn line, demonstrating the Fayoumi line's classification as a relatively NDV-resistant breed. Examination of the trachea transcriptome showed a large increase in immune cell infiltration in the trachea in both lines at all times postinfection. The pathways conserved across lines and at all three time points postinfection included iCOS-iCOSL signaling in T helper cells, NF-κB signaling, the role of nuclear factor of activated T cells in the regulation of the immune response, calcium-induced T lymphocyte apoptosis, phospholipase C signaling, and CD28 signaling in T helper cells. Although shared pathways were seen in the Fayoumi and Leghorn lines, each line showed unique responses as well. The downregulation of collagen and the activation of eukaryotic translation initiation factor 2 signaling in the Fayoumis relative to the Leghorns at 2 days postinfection may contribute to the resistance phenotype seen in the Fayoumis. This study provides a further understanding of host-pathogen interactions which could improve vaccine efficacy and, in combination with genome-wide association studies, has the potential to advance strategies for breeding chickens with enhanced resistance to NDV.",2017 May 5,"['Deist, Melissa S.', 'Gallardo, Rodrigo A.', 'Bunn, David A.', 'Kelly, Terra R.', 'Dekkers, Jack C. M.', 'Zhou, Huaijun', 'Lamont, Susan J.']",Clin Vaccine Immunol,,,True
0b28042cfd599260246af0e54cb2c14267d2755f,PMC,Editorial: Perspectives for the Next Generation of Virus Research: Spearheading the Use of Innovative Technologies and Methodologies,http://dx.doi.org/10.3389/fmicb.2017.00758,PMC5425463,28553261,CC BY,,2017 May 11,"['Yamamoto, Takatoki', 'Honda, Ayae', 'Sato, Toshinori', 'Ryo, Akihide']",Front Microbiol,,,False
83ded158834351502d802279e29b00a98d7cd4e7,PMC,Endotracheal Intubation Using a Direct Laryngoscope and the Protective Performances of Respirators: A Randomized Trial,http://dx.doi.org/10.1155/2017/7565706,PMC5425829,28536701,CC BY,"Purpose. Emergency physicians are at risk for infection during invasive procedures, and the respirators can reduce this risk. This study aimed to determine whether endotracheal intubation using direct laryngoscopes affected protection performances of respirators. Methods. A randomized crossover study of 24 emergency physicians was performed. We performed quantitative fit tests using respirators (cup type, fold type without a valve, and fold type with a valve) before and during intubation. The primary outcome was respirators' fit factors (FF), and secondary outcomes were acceptable protection (percentage of scores above 100 FF [FF%]). Results. 24 pieces of data were analyzed. Compared to fold-type respirator without a valve, FF and FF% values were lower when participants wore a cup-type respirator (200 FF [200-200] versus 200 FF [102.75–200], 100% [78.61–100] versus 74.16% [36.1–98.9]; all P < 0.05) or fold-type respirator with a valve (200 FF [200-200] versus 142.5 FF [63.50–200], 100% [76.10–100] versus 62.50% [8.13–100]; all P < 0.05). There were no significant differences in intubation time and success rate according to respirator types. Conclusions. Motion during endotracheal intubation using direct laryngoscopes influenced the protective performance of some respirators. Therefore, emergency physicians should identify and wear respirators that provide the best personalized fit for intended tasks.",2017 Apr 27,"['Lim, Taeho', 'Lee, Sanghyun', 'Oh, Jaehoon', 'Kang, Hyunggoo', 'Ahn, Chiwon', 'Song, Yeongtak', 'Lee, Juncheol', 'Shin, Hyungoo']",Biomed Res Int,,,True
a0e4e330c82c1b1a043345891bef190baa73980f,PMC,Incidence and comparison of retrospective and prospective data on respiratory and gastrointestinal infections in German households,http://dx.doi.org/10.1186/s12879-017-2434-5,PMC5426066,28490316,CC BY,"BACKGROUND: Acute respiratory infections (ARI) and acute gastrointestinal infections (AGI) are the most common childhood infections, and corresponding data can either be collected prospectively or retrospectively. The aim of this study was to estimate the incidence of respiratory and gastrointestinal episodes in German households with children attending day care and to compare results of prospective and retrospective data collection. METHODS: We conducted a 4 months prospective cohort study in the winter period 2014/2015 and recruited parents of children aged 0–6 years in 75 day care centers in Braunschweig, Lower Saxony, Germany. For all household members, we collected information on episodes of ARI and AGI. We applied prospective data collection in one study arm and retrospective data collection with a reporting period of 2 months in the other. Poisson regression was used to model monthly incidence rates for both study arms. RESULTS: In total, 100 households (including 404 persons) participated in the retrospective group and 77 households (282 persons) in the prospective group. Incidence estimates for ARI (retrospective group: 0.52 per person month, prospective group: 0.47) were higher than for AGI (retrospective group: 0.14, prospective group: 0.13). The adjusted incidence estimates were similar in both study arms for ARI (incidence rate ratio for retrospective versus prospective data collection: 1.11 [confidence interval (CI) 95% 0.99; 1.24], p = 0.42) as well as for AGI (1.10 [CI 95% 0.89; 1.37], p = 0.27). CONCLUSION: If there is no need to collect biomaterials or data on severity of the diseases, incidence of infections in the household setting over a short time period (2 months) can be assessed retrospectively. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-017-2434-5) contains supplementary material, which is available to authorized users.",2017 May 11,"['Schlinkmann, Kristin Maria', 'Bakuli, Abhishek', 'Mikolajczyk, Rafael']",BMC Infect Dis,,,True
1a19e1b8f4e8c0fe67b2cab9eef2c95cfc44f5ed,PMC,Between Securitisation and Neglect: Managing Ebola at the Borders of Global Health,http://dx.doi.org/10.1017/mdh.2017.6,PMC5426310,28260567,CC BY,"In 2014 the World Health Organization (WHO) was widely criticised for failing to anticipate that an outbreak of Ebola in a remote forested region of south-eastern Guinea would trigger a public health emergency of international concern (pheic). In explaining the WHO’s failure, critics have pointed to structural restraints on the United Nations organisation and a leadership ‘vacuum’ in Geneva, among other factors. This paper takes a different approach. Drawing on internal WHO documents and interviews with key actors in the epidemic response, I argue that the WHO’s failure is better understood as a consequence of Ebola’s shifting medical identity and of triage systems for managing emerging infectious disease (EID) risks. Focusing on the discursive and non-discursive practices that produced Ebola as a ‘problem’ for global health security, I argue that by 2014 Ebola was no longer regarded as a paradigmatic EID and potential biothreat so much as a neglected tropical disease. The result was to relegate Ebola to the fringes of biosecurity concerns just at the moment when the virus was crossing international borders in West Africa and triggering large urban outbreaks for the first time. Ebola’s fluctuating medical identity also helps explain the prominence of fear and rumours during the epidemic and social resistance to Ebola control measures. Contrasting the WHO’s delay over declaring a pheic in 2014, with its rapid declaration of pheics in relation to H1N1 swine flu in 2009 and polio in 2014, I conclude that such ‘missed alarms’ may be an inescapable consequence of pandemic preparedness systems that seek to rationalise responses to the emergence of new diseases.",2017 Apr,"Honigsbaum, Mark",Med Hist,,,True
17413f651645c2b9c92555e9ce1404b9290eccab,PMC,Non-human primate orthologues of TMPRSS2 cleave and activate the influenza virus hemagglutinin,http://dx.doi.org/10.1371/journal.pone.0176597,PMC5426610,28493964,CC BY,"The cellular serine protease TMPRSS2, a member of the type II transmembrane serine protease (TTSP) family, cleaves and activates the hemagglutinin of influenza A viruses (FLUAV) in cell culture and is essential for spread of diverse FLUAV in mice. Non-human primates (NHP), in particular rhesus and cynomolgus macaques, serve as animal models for influenza and experimental FLUAV infection of common marmosets has recently also been reported. However, it is currently unknown whether the NHP orthologues of human TMPRSS2 cleave and activate FLUAV hemagglutinin and contribute to viral spread in respiratory tissue. Here, we cloned and functionally analyzed the macaque and marmoset orthologues of human TMPRSS2. In addition, we analyzed the macaque orthologues of human TMPRSS4 and HAT, which also belong to the TTSP family. We found that all NHP orthologues of human TMPRSS2, TMPRSS4 and HAT cleave and activate HA upon directed expression and provide evidence that endogenous TMPRSS2 is expressed in the respiratory epithelium of rhesus macaques. Finally, we demonstrate that a serine protease inhibitor active against TMPRSS2 suppresses FLUAV spread in precision-cut lung slices of human, macaque and marmoset origin. These results indicate that FLUAV depends on serine protease activity for spread in diverse NHP and in humans. Moreover, our findings suggest that macaques and marmosets may serve as models to study FLUAV activation by TMPRSS2 in human patients.",2017 May 11,"['Zmora, Pawel', 'Molau-Blazejewska, Paulina', 'Bertram, Stephanie', 'Walendy-Gnirß, Kerstin', 'Nehlmeier, Inga', 'Hartleib, Anika', 'Moldenhauer, Anna-Sophie', 'Konzok, Sebastian', 'Dehmel, Susann', 'Sewald, Katherina', 'Brinkmann, Constantin', 'Curths, Christoph', 'Knauf, Sascha', 'Gruber, Jens', 'Mätz-Rensing, Kerstin', 'Dahlmann, Franziska', 'Braun, Armin', 'Pöhlmann, Stefan']",PLoS One,,,True
621c8306765f418717c3de4497c2dace5f8a9c73,PMC,The host ubiquitin-dependent segregase VCP/p97 is required for the onset of human cytomegalovirus replication,http://dx.doi.org/10.1371/journal.ppat.1006329,PMC5426786,28494016,CC BY,"The human cytomegalovirus major immediate early proteins IE1 and IE2 are critical drivers of virus replication and are considered pivotal in determining the balance between productive and latent infection. IE1 and IE2 are derived from the same primary transcript by alternative splicing and regulation of their expression likely involves a complex interplay between cellular and viral factors. Here we show that knockdown of the host ubiquitin-dependent segregase VCP/p97, results in loss of IE2 expression, subsequent suppression of early and late gene expression and, ultimately, failure in virus replication. RNAseq analysis showed increased levels of IE1 splicing, with a corresponding decrease in IE2 splicing following VCP knockdown. Global analysis of viral transcription showed the expression of a subset of viral genes is not reduced despite the loss of IE2 expression, including UL112/113. Furthermore, Immunofluorescence studies demonstrated that VCP strongly colocalised with the viral replication compartments in the nucleus. Finally, we show that NMS-873, a small molecule inhibitor of VCP, is a potent HCMV antiviral with potential as a novel host targeting therapeutic for HCMV infection.",2017 May 11,"['Lin, Yao-Tang', 'Prendergast, James', 'Grey, Finn']",PLoS Pathog,,,True
a58c4de6acdb5e333840e07494c95b0e81b6e52e,PMC,Tracking zoonotic pathogens using blood-sucking flies as 'flying syringes',http://dx.doi.org/10.7554/eLife.22069,PMC5426900,28347401,CC BY,"About 60% of emerging infectious diseases in humans are of zoonotic origin. Their increasing number requires the development of new methods for early detection and monitoring of infectious agents in wildlife. Here, we investigated whether blood meals from hematophagous flies could be used to identify the infectious agents circulating in wild vertebrates. To this aim, 1230 blood-engorged flies were caught in the forests of Gabon. Identified blood meals (30%) were from 20 vertebrate species including mammals, birds and reptiles. Among them, 9% were infected by different extant malaria parasites among which some belonged to known parasite species, others to new parasite species or to parasite lineages for which only the vector was known. This study demonstrates that using hematophagous flies as ‘flying syringes’ constitutes an interesting approach to investigate blood-borne pathogen diversity in wild vertebrates and could be used as an early detection tool of zoonotic pathogens. DOI: http://dx.doi.org/10.7554/eLife.22069.001",,"['Bitome-Essono, Paul-Yannick', 'Ollomo, Benjamin', 'Arnathau, Céline', 'Durand, Patrick', 'Mokoudoum, Nancy Diamella', 'Yacka-Mouele, Lauriane', 'Okouga, Alain-Prince', 'Boundenga, Larson', 'Mve-Ondo, Bertrand', 'Obame-Nkoghe, Judicaël', 'Mbehang-Nguema, Philippe', 'Njiokou, Flobert', 'Makanga, Boris', 'Wattier, Rémi', 'Ayala, Diego', 'Ayala, Francisco J', 'Renaud, Francois', 'Rougeron, Virginie', 'Bretagnolle, Francois', 'Prugnolle, Franck', 'Paupy, Christophe']",eLife.; 6:e22069,,,True
97103b4636fa1bf6d381d6bda00d0e5d126b331c,PMC,A Role for Neutrophils in Viral Respiratory Disease,http://dx.doi.org/10.3389/fimmu.2017.00550,PMC5427094,28553293,CC BY,"Neutrophils are immune cells that are well known to be present during many types of lung diseases associated with acute respiratory distress syndrome (ARDS) and may contribute to acute lung injury. Neutrophils are poorly studied with respect to viral infection, and specifically to respiratory viral disease. Influenza A virus (IAV) infection is the cause of a respiratory disease that poses a significant global public health concern. Influenza disease presents as a relatively mild and self-limiting although highly pathogenic forms exist. Neutrophils increase in the respiratory tract during infection with mild seasonal IAV, moderate and severe epidemic IAV infection, and emerging highly pathogenic avian influenza (HPAI). During severe influenza pneumonia and HPAI infection, the number of neutrophils in the lower respiratory tract is correlated with disease severity. Thus, comparative analyses of the relationship between IAV infection and neutrophils provide insights into the relative contribution of host and viral factors that contribute to disease severity. Herein, we review the contribution of neutrophils to IAV disease pathogenesis and to other respiratory virus infections.",2017 May 12,"['Camp, Jeremy V.', 'Jonsson, Colleen B.']",Front Immunol,,,True
32e9da5d0766c5b192ba52080d05a9d91edf74eb,PMC,Genome Sequence of a Bovine Rhinitis B Virus Identified in Cattle in Sweden,http://dx.doi.org/10.1128/genomeA.00172-17,PMC5427196,28495761,CC BY,"A bovine rhinitis B virus, identified in a calf from Sweden, was genetically characterized. The complete polyprotein was recovered, and phylogenetic analysis showed that this virus has the highest similarity to a bovine rhinitis B virus previously identified in Mexico.",2017 May 11,"['Blomström, Anne-Lie', 'Oma, Veslemøy', 'Khatri, Mamata', 'Hansen, Hanne H.', 'Stokstad, Maria', 'Berg, Mikael', 'Myrmel, Mette']",Genome Announc,,,True
ea85420ea72fab3346afc8aaf42b17f571b99a85,PMC,Solving the master equation for Indels,http://dx.doi.org/10.1186/s12859-017-1665-1,PMC5427538,28494756,CC BY,"BACKGROUND: Despite the long-anticipated possibility of putting sequence alignment on the same footing as statistical phylogenetics, theorists have struggled to develop time-dependent evolutionary models for indels that are as tractable as the analogous models for substitution events. MAIN TEXT: This paper discusses progress in the area of insertion-deletion models, in view of recent work by Ezawa (BMC Bioinformatics 17:304, 2016); (BMC Bioinformatics 17:397, 2016); (BMC Bioinformatics 17:457, 2016) on the calculation of time-dependent gap length distributions in pairwise alignments, and current approaches for extending these approaches from ancestor-descendant pairs to phylogenetic trees. CONCLUSIONS: While approximations that use finite-state machines (Pair HMMs and transducers) currently represent the most practical approach to problems such as sequence alignment and phylogeny, more rigorous approaches that work directly with the matrix exponential of the underlying continuous-time Markov chain also show promise, especially in view of recent advances.",2017 May 12,"Holmes, Ian H.",BMC Bioinformatics,,,True
c1b14e0ea5b125b3e32a7baf0456a453943f2c32,PMC,Complete Genomic and Ultrastructural Analysis of a Nam Dinh Virus Isolated from Culex pipiens quinquefasciatus in China*,http://dx.doi.org/10.1038/s41598-017-00340-3,PMC5428213,28325899,CC BY,"The Nam Dinh virus (NDiV) was isolated from Culex quinquefasciatus in Shenzhen, China, for the first time, in 2011. In this study, we characterized the ultrastructure of NDiV, determined its complete genome sequence and made comparisons with other known nidoviruses. Electron microscopic observation revealed that the NDiV strain isolated in China produced viral nucleocapsid-like particles and vesicles in host cells. The extracellular virions were enveloped and were spherical with short spikes. The complete genome sequence of the newly isolated NDiV was submitted to the GenBank database (GenBank accession number KF522691). Sequencing of the viral genome showed that the homologies of NDiV isolated in China and Vietnam were greater than 94.0% and 89.0% at the nucleotide and amino acid sequence levels, respectively. Moreover, gene substitution was detected, whereas insertions and deletions were not. A phylogenetic tree analysis showed that these viruses belong to the genus Alphamesonivirus1 of the family Mesoniviridae. The similarity between the two viruses regarding morphological and molecular biological characteristics indicates that the molecular genetics of NDiV are conservative and that the regional differences are unlikely to have a significant effect. This is the first report of the isolation and complete sequencing of a mesonivirus in mainland China.",2017 Mar 21,"['Zhou, Jianming', 'Jin, Yujuan', 'Chen, Yingjian', 'Li, Jingmei', 'Zhang, Qiwen', 'Xie, Xianqing', 'Gan, Liping', 'Liu, Qu']",Sci Rep,,,False
1f29ce1525b32b7b954901bc5c04aaffe615ccd9,PMC,Complete Genomic and Ultrastructural Analysis of a Nam Dinh Virus Isolated from Culex pipiens quinquefasciatus in China*,http://dx.doi.org/10.1038/s41598-017-00340-3,PMC5428213,28325899,CC BY,"The Nam Dinh virus (NDiV) was isolated from Culex quinquefasciatus in Shenzhen, China, for the first time, in 2011. In this study, we characterized the ultrastructure of NDiV, determined its complete genome sequence and made comparisons with other known nidoviruses. Electron microscopic observation revealed that the NDiV strain isolated in China produced viral nucleocapsid-like particles and vesicles in host cells. The extracellular virions were enveloped and were spherical with short spikes. The complete genome sequence of the newly isolated NDiV was submitted to the GenBank database (GenBank accession number KF522691). Sequencing of the viral genome showed that the homologies of NDiV isolated in China and Vietnam were greater than 94.0% and 89.0% at the nucleotide and amino acid sequence levels, respectively. Moreover, gene substitution was detected, whereas insertions and deletions were not. A phylogenetic tree analysis showed that these viruses belong to the genus Alphamesonivirus1 of the family Mesoniviridae. The similarity between the two viruses regarding morphological and molecular biological characteristics indicates that the molecular genetics of NDiV are conservative and that the regional differences are unlikely to have a significant effect. This is the first report of the isolation and complete sequencing of a mesonivirus in mainland China.",2017 Mar 21,"['Zhou, Jianming', 'Jin, Yujuan', 'Chen, Yingjian', 'Li, Jingmei', 'Zhang, Qiwen', 'Xie, Xianqing', 'Gan, Liping', 'Liu, Qu']",Sci Rep,,,True
8c71f856263c447ba7983e1f7087259008ca8505,PMC,A permanent host shift of rabies virus from Chiroptera to Carnivora associated with recombination,http://dx.doi.org/10.1038/s41598-017-00395-2,PMC5428239,28325933,CC BY,"Bat virus host shifts can result in the spread of diseases with significant effects. The rabies virus (RABV) is able to infect almost all mammals and is therefore a useful model for the study of host shift mechanisms. Carnivore RABVs originated from two historical host shifts from bat viruses. To reveal the genetic pathways by which bat RABVs changed their host tropism from bats to carnivores, we investigated the second permanent bat-to-carnivore shift resulting in two carnivore variants, known as raccoon RABV (RRV) and south-central skunk RABV (SCSKV). We found that their glycoprotein (G) genes are the result of recombination between an American bat virus and a carnivore virus. This recombination allowed the bat RABV to acquire the head of the G-protein ectodomain of the carnivore virus. This region is involved in receptor recognition and binding, response to changes in the pH microenvironment, trimerization of G proteins, and cell-to-cell transmission during the viral infection. Therefore, this recombination event may have significantly improved the variant’s adaptability to carnivores, altering its host tropism and thus leading to large-scale epidemics in striped skunk and raccoon.",2017 Mar 21,"['Ding, Nai-Zheng', 'Xu, Dong-Shuai', 'Sun, Yuan-Yuan', 'He, Hong-Bin', 'He, Cheng-Qiang']",Sci Rep,,,True
b674a61784ba6e4aa8d6d9236cf620bd79090afe,PMC,Accelerated disease progression and robust innate host response in aged SIVmac239-infected Chinese rhesus macaques is associated with enhanced immunosenescence,http://dx.doi.org/10.1038/s41598-017-00084-0,PMC5428349,28232735,CC BY,"The elderly population infected with HIV-1 is often characterized by the rapid AIDS progression and poor treatment outcome, possibly because of immunosenescence resulting from both HIV infection and aging. However, this hypothesis remains to be fully tested. Here, we studied 6 young and 12 old Chinese rhesus macaques (ChRM) over the course of three months after simian immunodeficiency virus (SIV) SIVmac239 infection. Old ChRM showed a higher risk of accelerated AIDS development than did young macaques, owing to rapidly elevated plasma viral loads and decreased levels of CD4(+) T cells. The low frequency of naïve CD4(+) T cells before infection was strongly predictive of an increased disease progression, whereas the severe depletion of CD4(+) T cells and the rapid proliferation of naïve lymphocytes accelerated the exhaustion of naïve lymphocytes in old ChRM. Moreover, in old ChRM, a robust innate host response with defective regulation was associated with a compensation for naïve T cell depletion and a high level of immune activation. Therefore, we suggest that immunosenescence plays an important role in the accelerated AIDS progression in elderly individuals and that SIV-infected old ChRM may be a favorable model for studying AIDS pathogenesis and researching therapies for elderly AIDS patients.",2017 Feb 24,"['Zheng, Hong-Yi', 'Zhang, Ming-Xu', 'Chen, Min', 'Jiang, Jin', 'Song, Jia-Hao', 'Lian, Xiao-Dong', 'Tian, Ren-Rong', 'Zhang, Xiao-Liang', 'Zhang, Lin-Tao', 'Pang, Wei', 'Zhang, Gao-Hong', 'Zheng, Yong-Tang']",Sci Rep,,,False
9bd22fc1297bd20710ca26f6e79b6339d576bb74,PMC,Accelerated disease progression and robust innate host response in aged SIVmac239-infected Chinese rhesus macaques is associated with enhanced immunosenescence,http://dx.doi.org/10.1038/s41598-017-00084-0,PMC5428349,28232735,CC BY,"The elderly population infected with HIV-1 is often characterized by the rapid AIDS progression and poor treatment outcome, possibly because of immunosenescence resulting from both HIV infection and aging. However, this hypothesis remains to be fully tested. Here, we studied 6 young and 12 old Chinese rhesus macaques (ChRM) over the course of three months after simian immunodeficiency virus (SIV) SIVmac239 infection. Old ChRM showed a higher risk of accelerated AIDS development than did young macaques, owing to rapidly elevated plasma viral loads and decreased levels of CD4(+) T cells. The low frequency of naïve CD4(+) T cells before infection was strongly predictive of an increased disease progression, whereas the severe depletion of CD4(+) T cells and the rapid proliferation of naïve lymphocytes accelerated the exhaustion of naïve lymphocytes in old ChRM. Moreover, in old ChRM, a robust innate host response with defective regulation was associated with a compensation for naïve T cell depletion and a high level of immune activation. Therefore, we suggest that immunosenescence plays an important role in the accelerated AIDS progression in elderly individuals and that SIV-infected old ChRM may be a favorable model for studying AIDS pathogenesis and researching therapies for elderly AIDS patients.",2017 Feb 24,"['Zheng, Hong-Yi', 'Zhang, Ming-Xu', 'Chen, Min', 'Jiang, Jin', 'Song, Jia-Hao', 'Lian, Xiao-Dong', 'Tian, Ren-Rong', 'Zhang, Xiao-Liang', 'Zhang, Lin-Tao', 'Pang, Wei', 'Zhang, Gao-Hong', 'Zheng, Yong-Tang']",Sci Rep,,,True
9d70e95d1ec65bab64f331ee0b305c4051d7be38,PMC,Hydrogen sulfide ameliorates chronic renal failure in rats by inhibiting apoptosis and inflammation through ROS/MAPK and NF-κB signaling pathways,http://dx.doi.org/10.1038/s41598-017-00557-2,PMC5428696,28352125,CC BY,"Chronic renal failure (CRF) is a major public health problem worldwide. Hydrogen sulfide (H(2)S) plays important roles in renal physiological and pathophysiological processes. However, whether H(2)S could protect against CRF in rats remains unclear. In this study, we found that H(2)S alleviated gentamicin-induced nephrotoxicity by reducing reactive oxygen species (ROS)-mediated apoptosis in normal rat kidney-52E cells. We demonstrated that H(2)S significantly improved the kidney structure and function of CRF rats. We found that H(2)S decreased the protein levels of Bax, Caspase-3, and Cleaved-caspase-3, but increased the expression of Bcl-2. Treatment with H(2)S reduced the levels of malondialdehyde and ROS and increased the activities of superoxide dismutase and glutathione peroxidase. H(2)S significantly abolished the phosphorylation of extracellular signal-regulated protein kinase 1/2, c-Jun N-terminal kinase, and p38 in the kidney of CRF rats. Furthermore, H(2)S decreased the expression levels of tumor necrosis factor-α, interleukin (IL)-6, IL-10, and monocyte chemoattractant protein-1, as well as the protein levels of p50, p65, and p-p65 in the kidney of CRF rats. In conclusion, H(2)S could ameliorate adenine-induced CRF in rats by inhibiting apoptosis and inflammation through ROS/mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways.",2017 Mar 28,"['Wu, Dongdong', 'Luo, Ning', 'Wang, Lianqu', 'Zhao, Zhijun', 'Bu, Hongmin', 'Xu, Guoliang', 'Yan, Yongjun', 'Che, Xinping', 'Jiao, Zhiling', 'Zhao, Tengfu', 'Chen, Jingtao', 'Ji, Ailing', 'Li, Yanzhang', 'Lee, Garrick D.']",Sci Rep,,,False
f9700deed61ea92d41891cf29eccddac0ee0ca15,PMC,Hydrogen sulfide ameliorates chronic renal failure in rats by inhibiting apoptosis and inflammation through ROS/MAPK and NF-κB signaling pathways,http://dx.doi.org/10.1038/s41598-017-00557-2,PMC5428696,28352125,CC BY,"Chronic renal failure (CRF) is a major public health problem worldwide. Hydrogen sulfide (H(2)S) plays important roles in renal physiological and pathophysiological processes. However, whether H(2)S could protect against CRF in rats remains unclear. In this study, we found that H(2)S alleviated gentamicin-induced nephrotoxicity by reducing reactive oxygen species (ROS)-mediated apoptosis in normal rat kidney-52E cells. We demonstrated that H(2)S significantly improved the kidney structure and function of CRF rats. We found that H(2)S decreased the protein levels of Bax, Caspase-3, and Cleaved-caspase-3, but increased the expression of Bcl-2. Treatment with H(2)S reduced the levels of malondialdehyde and ROS and increased the activities of superoxide dismutase and glutathione peroxidase. H(2)S significantly abolished the phosphorylation of extracellular signal-regulated protein kinase 1/2, c-Jun N-terminal kinase, and p38 in the kidney of CRF rats. Furthermore, H(2)S decreased the expression levels of tumor necrosis factor-α, interleukin (IL)-6, IL-10, and monocyte chemoattractant protein-1, as well as the protein levels of p50, p65, and p-p65 in the kidney of CRF rats. In conclusion, H(2)S could ameliorate adenine-induced CRF in rats by inhibiting apoptosis and inflammation through ROS/mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways.",2017 Mar 28,"['Wu, Dongdong', 'Luo, Ning', 'Wang, Lianqu', 'Zhao, Zhijun', 'Bu, Hongmin', 'Xu, Guoliang', 'Yan, Yongjun', 'Che, Xinping', 'Jiao, Zhiling', 'Zhao, Tengfu', 'Chen, Jingtao', 'Ji, Ailing', 'Li, Yanzhang', 'Lee, Garrick D.']",Sci Rep,,,True
00a664b48014274712296dc71d6bc77846aff6e3,PMC,Avian and human influenza virus compatible sialic acid receptors in little brown bats,http://dx.doi.org/10.1038/s41598-017-00793-6,PMC5429623,28386114,CC BY,"Influenza A viruses (IAVs) continue to threaten animal and human health globally. Bats are asymptomatic reservoirs for many zoonotic viruses. Recent reports of two novel IAVs in fruit bats and serological evidence of avian influenza virus (AIV) H9 infection in frugivorous bats raise questions about the role of bats in IAV epidemiology. IAVs bind to sialic acid (SA) receptors on host cells, and it is widely believed that hosts expressing both SA α2,3-Gal and SA α2,6-Gal receptors could facilitate genetic reassortment of avian and human IAVs. We found abundant co-expression of both avian (SA α2,3-Gal) and human (SA α2,6-Gal) type SA receptors in little brown bats (LBBs) that were compatible with avian and human IAV binding. This first ever study of IAV receptors in a bat species suggest that LBBs, a widely-distributed bat species in North America, could potentially be co-infected with avian and human IAVs, facilitating the emergence of zoonotic strains.",2017 Apr 6,"['Chothe, Shubhada K.', 'Bhushan, Gitanjali', 'Nissly, Ruth H.', 'Yeh, Yin-Ting', 'Brown, Justin', 'Turner, Gregory', 'Fisher, Jenny', 'Sewall, Brent J.', 'Reeder, DeeAnn M.', 'Terrones, Mauricio', 'Jayarao, Bhushan M.', 'Kuchipudi, Suresh V.']",Sci Rep,,,False
0a037565ead5cb2ee8dbdd7f6a0e381dd4b7ad83,PMC,Avian and human influenza virus compatible sialic acid receptors in little brown bats,http://dx.doi.org/10.1038/s41598-017-00793-6,PMC5429623,28386114,CC BY,"Influenza A viruses (IAVs) continue to threaten animal and human health globally. Bats are asymptomatic reservoirs for many zoonotic viruses. Recent reports of two novel IAVs in fruit bats and serological evidence of avian influenza virus (AIV) H9 infection in frugivorous bats raise questions about the role of bats in IAV epidemiology. IAVs bind to sialic acid (SA) receptors on host cells, and it is widely believed that hosts expressing both SA α2,3-Gal and SA α2,6-Gal receptors could facilitate genetic reassortment of avian and human IAVs. We found abundant co-expression of both avian (SA α2,3-Gal) and human (SA α2,6-Gal) type SA receptors in little brown bats (LBBs) that were compatible with avian and human IAV binding. This first ever study of IAV receptors in a bat species suggest that LBBs, a widely-distributed bat species in North America, could potentially be co-infected with avian and human IAVs, facilitating the emergence of zoonotic strains.",2017 Apr 6,"['Chothe, Shubhada K.', 'Bhushan, Gitanjali', 'Nissly, Ruth H.', 'Yeh, Yin-Ting', 'Brown, Justin', 'Turner, Gregory', 'Fisher, Jenny', 'Sewall, Brent J.', 'Reeder, DeeAnn M.', 'Terrones, Mauricio', 'Jayarao, Bhushan M.', 'Kuchipudi, Suresh V.']",Sci Rep,,,True
212b5e2ca9c78f0864f5a8540b36b3c18ad06d27,PMC,Multiple Immunosuppressive Effects of CpG-c41 on Intracellular TLR-Mediated Inflammation,http://dx.doi.org/10.1155/2017/6541729,PMC5429961,28539706,CC BY,"A growing body of literature suggests that most chronic autoimmune diseases are associated with inappropriate inflammation mediated by Toll-like receptor (TLR) 3, TLR7/8, or TLR9. Therefore, research into blocking TLR activation to treat these disorders has become a hot topic. Here, we report the immunomodulatory properties of a nonstimulatory CpG-containing oligodeoxynucleotide (CpG-ODN), CpG-c41, which had previously only been known as a TLR9 antagonist. In this study, we found that both in vitro and in vivo CpG-c41 decreased levels of various proinflammatory factors that were induced by single activation or coactivation of intracellular TLRs, but not membrane-bound TLRs, no matter what downstream signal pathways the TLRs depend on. Moreover, CpG-c41 attenuated excessive inflammation in the imiquimod-induced psoriasis-like mouse model of skin inflammation by suppressing immune cell infiltration and release of inflammatory factors. We also found evidence that the immunosuppressive effects of CpG-c41 on other intracellular TLRs are mediated by a TLR9-independent mechanism. These results suggest that CpG-c41 acts as an upstream of signaling cascades, perhaps on the processes of ligand internalization and transfer. Taken together, these results suggest that CpG-c41 disrupts various aspects of intracellular TLR activation and provides a deeper insight into the regulation of innate immunity.",2017 Apr 30,"['Liu, Wancheng', 'Yang, Xuejiao', 'Wang, Ning', 'Fan, Shijun', 'Zhu, Yuanfeng', 'Zheng, Xinchuan', 'Li, Yan']",Mediators Inflamm,,,True
53a61d8113ac61c3a987782564a2ee4f61c3e254,PMC,"A joint analysis of influenza-associated hospitalizations and mortality in Hong Kong, 1998–2013",http://dx.doi.org/10.1038/s41598-017-01021-x,PMC5430505,28428558,CC BY,"Influenza viruses may cause severe human infections leading to hospitalization or death. Linear regression models were fitted to population-based data on hospitalizations and deaths. Surveillance data on influenza virus activity permitted inference on influenza-associated hospitalizations and deaths. The ratios of these estimates were used as a potential indicator of severity. Influenza was associated with 431 (95% CrI: 358–503) respiratory deaths and 12,700 (95% CrI: 11,700–13,700) respiratory hospitalizations per year. Majority of the excess deaths occurred in persons ≥65 y of age. The ratios of deaths to hospitalizations in adults ≥65 y were significantly higher for influenza A(H1N1) and A(H1N1)pdm09 compared to A(H3N2) and B. Substantial disease burden associated with influenza viruses were estimated in Hong Kong particularly among children and elderly in 1998–2013. Infections with influenza A(H1N1) was suggested to be more serious than A(H3N2) in older adults.",2017 Apr 20,"['Wu, Peng', 'Presanis, Anne M.', 'Bond, Helen S.', 'Lau, Eric H. Y.', 'Fang, Vicky J.', 'Cowling, Benjamin J.']",Sci Rep,,,True
8ce8f62c69841b1d1db1df313b89849348370cc1,PMC,Antiviral activities of Schizonepeta tenuifolia Briq. against enterovirus 71 in vitro and in vivo,http://dx.doi.org/10.1038/s41598-017-01110-x,PMC5430552,28428548,CC BY,"No effective drug is currently available for treatment of enterovirus 71 (EV71) infection. Schizonepeta tenuifolia Briq. (ST) has been used as a herbal constituent of traditional Chinese medicine. We studied whether the aqueous extract of Schizonepeta tenuifolia Briq (STE) has antiviral activity. STE inhibited replication of EV71, as evident by its ability to diminish plaque formation and cytopathic effect induced by EV71, and to inhibit the synthesis of viral RNA and protein. Moreover, daily single-dose STE treatment significantly improved the survival of EV71-infected mice, and ameliorated the symptoms. Mechanistically, STE exerts multiple effects on enteroviral infection. Treatment with STE reduced viral attachment and entry; the cleavage of eukaryotic translation initiation factor 4 G (eIF4G) by EV71 protease, 2A(pro); virus-induced reactive oxygen species (ROS) formation; and relocation of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) from the nucleus to the cytoplasm. It was accompanied by a decline in EV71-associated hyperphosphorylation of p38 kinase and EPS15. It is plausible that STE may inhibit ROS-induced p38 kinase activation, and subsequent hnRNP A1 relocation and EPS15-mediated membrane trafficking in infected cells. These findings suggest that STE possesses anti-EV71 activities, and may serve as health food or candidate antiviral drug for protection against EV71.",2017 Apr 20,"['Chen, Sin-Guang', 'Cheng, Mei-Ling', 'Chen, Kuan-Hsing', 'Horng, Jim-Tong', 'Liu, Ching-Chuan', 'Wang, Shih-Min', 'Sakurai, Hiroaki', 'Leu, Yann-Lii', 'Wang, Shulhn-Der', 'Ho, Hung-Yao']",Sci Rep,,,False
b9eaf7c97ff51c43bbcf3ed0605c2a040fe8c588,PMC,Antiviral activities of Schizonepeta tenuifolia Briq. against enterovirus 71 in vitro and in vivo,http://dx.doi.org/10.1038/s41598-017-01110-x,PMC5430552,28428548,CC BY,"No effective drug is currently available for treatment of enterovirus 71 (EV71) infection. Schizonepeta tenuifolia Briq. (ST) has been used as a herbal constituent of traditional Chinese medicine. We studied whether the aqueous extract of Schizonepeta tenuifolia Briq (STE) has antiviral activity. STE inhibited replication of EV71, as evident by its ability to diminish plaque formation and cytopathic effect induced by EV71, and to inhibit the synthesis of viral RNA and protein. Moreover, daily single-dose STE treatment significantly improved the survival of EV71-infected mice, and ameliorated the symptoms. Mechanistically, STE exerts multiple effects on enteroviral infection. Treatment with STE reduced viral attachment and entry; the cleavage of eukaryotic translation initiation factor 4 G (eIF4G) by EV71 protease, 2A(pro); virus-induced reactive oxygen species (ROS) formation; and relocation of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) from the nucleus to the cytoplasm. It was accompanied by a decline in EV71-associated hyperphosphorylation of p38 kinase and EPS15. It is plausible that STE may inhibit ROS-induced p38 kinase activation, and subsequent hnRNP A1 relocation and EPS15-mediated membrane trafficking in infected cells. These findings suggest that STE possesses anti-EV71 activities, and may serve as health food or candidate antiviral drug for protection against EV71.",2017 Apr 20,"['Chen, Sin-Guang', 'Cheng, Mei-Ling', 'Chen, Kuan-Hsing', 'Horng, Jim-Tong', 'Liu, Ching-Chuan', 'Wang, Shih-Min', 'Sakurai, Hiroaki', 'Leu, Yann-Lii', 'Wang, Shulhn-Der', 'Ho, Hung-Yao']",Sci Rep,,,True
bbb571faf51f9bd1c140c033999634e4ae2791f4,PMC,Accessible areas in ecological niche comparisons of invasive species: Recognized but still overlooked,http://dx.doi.org/10.1038/s41598-017-01313-2,PMC5430674,28450747,CC BY,"Understanding biological invasions is crucial for their control and prevention. Specially, establishing whether invasive species operate within the constraint of conservative ecological niches, or if niche shifts occur at all commonly as part of the invasion process, is indispensable to identifying and anticipating potential areas of invasion. Ecological niche modeling (ENM) has been used to address such questions, but improvements and debate in study design, model evaluation, and methods are still needed to mature this field. We reanalyze data for Gray Squirrels (Sciurus carolinensis), native to North America, but invasive in Europe. Our main finding was that, when the analysis extent is established carefully based on analogous sets of environmental conditions, all evidence of niche shifts disappears, suggesting that previous reports of niche shifts for this species are artifacts of methods and interpretation, rather than biological reality. Niche conservatism should be tested only within appropriate, similar, environmental spaces that are accessible to both species or populations being compared, thus avoiding model extrapolation related to model transfers. Testing for environmental similarity between native and invaded areas is critical to identifying niche shifts during species invasion robustly, but also in applications of ENM to understanding temporal dimensions of niche dynamics.",2017 Apr 27,"['Qiao, Huijie', 'Escobar, Luis E.', 'Peterson, A. Townsend']",Sci Rep,,,False
af95b3932b07aabf277276810797aebe765c8859,PMC,Accessible areas in ecological niche comparisons of invasive species: Recognized but still overlooked,http://dx.doi.org/10.1038/s41598-017-01313-2,PMC5430674,28450747,CC BY,"Understanding biological invasions is crucial for their control and prevention. Specially, establishing whether invasive species operate within the constraint of conservative ecological niches, or if niche shifts occur at all commonly as part of the invasion process, is indispensable to identifying and anticipating potential areas of invasion. Ecological niche modeling (ENM) has been used to address such questions, but improvements and debate in study design, model evaluation, and methods are still needed to mature this field. We reanalyze data for Gray Squirrels (Sciurus carolinensis), native to North America, but invasive in Europe. Our main finding was that, when the analysis extent is established carefully based on analogous sets of environmental conditions, all evidence of niche shifts disappears, suggesting that previous reports of niche shifts for this species are artifacts of methods and interpretation, rather than biological reality. Niche conservatism should be tested only within appropriate, similar, environmental spaces that are accessible to both species or populations being compared, thus avoiding model extrapolation related to model transfers. Testing for environmental similarity between native and invaded areas is critical to identifying niche shifts during species invasion robustly, but also in applications of ENM to understanding temporal dimensions of niche dynamics.",2017 Apr 27,"['Qiao, Huijie', 'Escobar, Luis E.', 'Peterson, A. Townsend']",Sci Rep,,,True
e10eb45af8825e380c4c7df28487b597f2b0402e,PMC,Tissue Distribution of the MERS-Coronavirus Receptor in Bats,http://dx.doi.org/10.1038/s41598-017-01290-6,PMC5430768,28446791,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) has been shown to infect both humans and dromedary camels using dipeptidyl peptidase-4 (DPP4) as its receptor. The distribution of DPP4 in the respiratory tract tissues of humans and camels reflects MERS-CoV tropism. Apart from dromedary camels, insectivorous bats are suggested as another natural reservoir for MERS-like-CoVs. In order to gain insight on the tropism of these viruses in bats, we studied the DPP4 distribution in the respiratory and extra-respiratory tissues of two frugivorous bat species (Epomophorus gambianus and Rousettus aegyptiacus) and two insectivorous bat species (Pipistrellus pipistrellus and Eptesicus serotinus). In the frugivorous bats, DPP4 was present in epithelial cells of both the respiratory and the intestinal tract, similar to what has been reported for camels and humans. In the insectivorous bats, however, DPP4 expression in epithelial cells of the respiratory tract was almost absent. The preferential expression of DPP4 in the intestinal tract of insectivorous bats, suggests that transmission of MERS-like-CoVs mainly occurs via the fecal-oral route. Our results highlight differences in the distribution of DPP4 expression among MERS-CoV susceptible species, which might influence variability in virus tropism, pathogenesis and transmission route.",2017 Apr 26,"['Widagdo, W.', 'Begeman, Lineke', 'Schipper, Debby', 'Run, Peter R. van', 'Cunningham, Andrew A.', 'Kley, Nils', 'Reusken, Chantal B.', 'Haagmans, Bart L.', 'van den Brand, Judith M. A.']",Sci Rep,,,True
a55fe997f40a68ed1e3169a8e6d8c5df4c91e34e,PMC,Changes in the Prevalence of HBsAg and HBeAg: a Study of 8696 Parturients in a Well Vaccinated Area,http://dx.doi.org/10.1038/s41598-017-01234-0,PMC5430794,28450703,CC BY,"To elucidate the impact of a hepatitis B (HB) vaccination program on the prevalence of HB surface antigen (HBsAg) and HB envelope antigen (HBeAg) as well as the success rate of HBeAg clearance among parturients, we collected data on parturients who gave birth between 2000 and 2010, and recorded the HB status postpartum of those with positive HBeAg before birth. A total of 8696 parturients were enrolled, of whom 113 with prenatal positive HBeAg were invited back. The prevalence of HBsAg decreased over the study period, particularly in the vaccinated cohort, while there was no change in the prevalence of HBeAg. Foreign parturients had a higher HBeAg-positive rate and delayed HBeAg clearance, and those with a higher body mass index (>24 kg/m(2)) had earlier HBeAg clearance (51.9% vs. 23.9%, p = 0.005). Only 30% of the subjects who were positive for HBeAg before birth became negative 5 years after delivery. In conclusion, the downward trend in HB infection with more significance among vaccinated parturients reflects effective prevention and the impact of universal HB immunization. Nonetheless, aggressive follow-up is necessary for parturients who are persistently positive for HBeAg postpartum, as well as developing different public health policies for foreign parturients from endemic areas.",2017 Apr 27,"['Wu, Chen-Hsuan', 'Hsu, Te-Yao', 'Kung, Fu-Tsai', 'ChangChien, Chan-Chao', 'Tsai, Ching-Chang', 'Lu, Sheng-Nan']",Sci Rep,,,True
201f1645e5f06f5a00a8cee90caa4f403b3a1266,PMC,Peripheral blood AKAP7 expression as an early marker for lymphocyte-mediated post-stroke blood brain barrier disruption,http://dx.doi.org/10.1038/s41598-017-01178-5,PMC5430856,28446746,CC BY,"Our group recently identified 16 genes whose peripheral blood expression levels are differentially regulated in acute ischemic stroke. The purpose of this study was to determine whether the early expression levels of any of these 16 genes are predictive for post-stroke blood brain barrier (BBB) disruption. Transcriptional expression levels of candidate genes were measured in peripheral blood sampled from ischemic stroke patients at emergency department admission, and BBB permeability was assessed at 24 hour follow up via perfusion-weighted imaging. Early heightened expression levels of AKAP7, a gene encoding a protein kinase A-binding scaffolding molecule, were significantly associated with BBB disruption 24 hours post-hospital admission. We then determined that AKAP7 is predominantly expressed by lymphocytes in peripheral blood, and strongly co-expressed with ITGA3, a gene encoding the adhesion molecule integrin alpha 3. Subsequent in vitro experiments revealed that heightened expression of AKAP7 and ITGA3 in primary human lymphocytes is associated with a highly adherent phenotype. Collectively, our results suggest that AKAP7 expression levels may have clinical utility as a prognostic biomarker for post-stroke BBB complications, and are likely elevated early in patients who later develop post-stroke BBB disruption due to the presence of an invasive lymphocyte population in the peripheral blood.",2017 Apr 26,"['O’Connell, Grant C.', 'Treadway, Madison B.', 'Petrone, Ashley B.', 'Tennant, Connie S.', 'Lucke-Wold, Noelle', 'Chantler, Paul D.', 'Barr, Taura L.']",Sci Rep,,,False
4d1125dd2aac5fa05600973b570834950bbcbccc,PMC,Peripheral blood AKAP7 expression as an early marker for lymphocyte-mediated post-stroke blood brain barrier disruption,http://dx.doi.org/10.1038/s41598-017-01178-5,PMC5430856,28446746,CC BY,"Our group recently identified 16 genes whose peripheral blood expression levels are differentially regulated in acute ischemic stroke. The purpose of this study was to determine whether the early expression levels of any of these 16 genes are predictive for post-stroke blood brain barrier (BBB) disruption. Transcriptional expression levels of candidate genes were measured in peripheral blood sampled from ischemic stroke patients at emergency department admission, and BBB permeability was assessed at 24 hour follow up via perfusion-weighted imaging. Early heightened expression levels of AKAP7, a gene encoding a protein kinase A-binding scaffolding molecule, were significantly associated with BBB disruption 24 hours post-hospital admission. We then determined that AKAP7 is predominantly expressed by lymphocytes in peripheral blood, and strongly co-expressed with ITGA3, a gene encoding the adhesion molecule integrin alpha 3. Subsequent in vitro experiments revealed that heightened expression of AKAP7 and ITGA3 in primary human lymphocytes is associated with a highly adherent phenotype. Collectively, our results suggest that AKAP7 expression levels may have clinical utility as a prognostic biomarker for post-stroke BBB complications, and are likely elevated early in patients who later develop post-stroke BBB disruption due to the presence of an invasive lymphocyte population in the peripheral blood.",2017 Apr 26,"['O’Connell, Grant C.', 'Treadway, Madison B.', 'Petrone, Ashley B.', 'Tennant, Connie S.', 'Lucke-Wold, Noelle', 'Chantler, Paul D.', 'Barr, Taura L.']",Sci Rep,,,True
eb0e14fcbb82adb3ae8149dba0ac6133bbb1e7fe,PMC,The Rational Design of Therapeutic Peptides for Aminopeptidase N using a Substrate-Based Approach,http://dx.doi.org/10.1038/s41598-017-01542-5,PMC5431086,28465619,CC BY,"The M1 family of metalloproteases represents a large number of exopeptidases that cleave single amino acid residues from the N-terminus of peptide substrates. One member of this family that has been well studied is aminopeptidase N (APN), a multifunctional protease known to cleave biologically active peptides and aide in coronavirus entry. The proteolytic activity of APN promotes cancer angiogenesis and metastasis making it an important target for cancer therapy. To understand the substrate specificity of APN for the development of targeted inhibitors, we used a global substrate profiling method to determine the P1–P4′ amino acid preferences. The key structural features of the APN pharmacophore required for substrate recognition were elucidated by x-ray crystallography. By combining these substrate profiling and structural data, we were able to design a selective peptide inhibitor of APN that was an effective therapeutic both in vitro and in vivo against APN-expressing prostate cancer models.",2017 May 2,"['Joshi, Shilvi', 'Chen, Lang', 'Winter, Michael B.', 'Lin, Yi-Lun', 'Yang, Yang', 'Shapovalova, Mariya', 'Smith, Paige M.', 'Liu, Chang', 'Li, Fang', 'LeBeau, Aaron M.']",Sci Rep,,,False
dd9a2b263b1b66db904ed8a18dd6eba55e64bfff,PMC,The Rational Design of Therapeutic Peptides for Aminopeptidase N using a Substrate-Based Approach,http://dx.doi.org/10.1038/s41598-017-01542-5,PMC5431086,28465619,CC BY,"The M1 family of metalloproteases represents a large number of exopeptidases that cleave single amino acid residues from the N-terminus of peptide substrates. One member of this family that has been well studied is aminopeptidase N (APN), a multifunctional protease known to cleave biologically active peptides and aide in coronavirus entry. The proteolytic activity of APN promotes cancer angiogenesis and metastasis making it an important target for cancer therapy. To understand the substrate specificity of APN for the development of targeted inhibitors, we used a global substrate profiling method to determine the P1–P4′ amino acid preferences. The key structural features of the APN pharmacophore required for substrate recognition were elucidated by x-ray crystallography. By combining these substrate profiling and structural data, we were able to design a selective peptide inhibitor of APN that was an effective therapeutic both in vitro and in vivo against APN-expressing prostate cancer models.",2017 May 2,"['Joshi, Shilvi', 'Chen, Lang', 'Winter, Michael B.', 'Lin, Yi-Lun', 'Yang, Yang', 'Shapovalova, Mariya', 'Smith, Paige M.', 'Liu, Chang', 'Li, Fang', 'LeBeau, Aaron M.']",Sci Rep,,,True
f6407ba464c2853df02c667220f75d71b89d541d,PMC,CD163(+)CD204(+) tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma,http://dx.doi.org/10.1038/s41598-017-01661-z,PMC5431876,28496107,CC BY,"Tumor-associated macrophages (TAMs) promote cancer cell proliferation, invasion, and metastasis by producing various mediators. Although preclinical studies demonstrated that TAMs preferentially express CD163 and CD204, the TAM subsets in oral squamous cell carcinoma (OSCC) remain unknown. In this study, we examined the expression and role of TAM subsets in OSCC. Forty-six patients with OSCC were analyzed for expression of TAMs in biopsy samples by immunohistochemistry. We examined TAM subsets and their production of immune suppressive molecules (IL-10 and PD-L1) in peripheral blood mononuclear cells from three OSCC patients by flow cytometry. CD163 was detected around the tumor or connective tissue, while CD204 was detected in/around the tumors. Flow cytometric analysis revealed that CD163(+)CD204(+) TAMs strongly produced IL-10 and PD-L1 in comparison with CD163(+)CD204(−) and CD163(−)CD204(+) TAMs. Furthermore, the number of activated CD3(+) T cells after co-culture with CD163(+)CD204(+) TAMs was significantly lower than that after co-culture with other TAM subsets. In clinical findings, the number of CD163(+)CD204(+) TAMs was negatively correlated with that of CD25(+) cells and 5-year progression-free survival. These results suggest that CD163(+)CD204(+) TAMs possibly play a key role in the invasion and metastasis of OSCC by T-cell regulation via IL-10 and PD-L1 production.",2017 May 11,"['Kubota, Keigo', 'Moriyama, Masafumi', 'Furukawa, Sachiko', 'Rafiul, Haque A. S. M.', 'Maruse, Yasuyuki', 'Jinno, Teppei', 'Tanaka, Akihiko', 'Ohta, Miho', 'Ishiguro, Noriko', 'Yamauchi, Masaaki', 'Sakamoto, Mizuki', 'Maehara, Takashi', 'Hayashida, Jun-Nosuke', 'Kawano, Shintaro', 'Kiyoshima, Tamotsu', 'Nakamura, Seiji']",Sci Rep,,,False
15ca0457de2d05a3796f024899edc9c55c86e4ba,PMC,CD163(+)CD204(+) tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma,http://dx.doi.org/10.1038/s41598-017-01661-z,PMC5431876,28496107,CC BY,"Tumor-associated macrophages (TAMs) promote cancer cell proliferation, invasion, and metastasis by producing various mediators. Although preclinical studies demonstrated that TAMs preferentially express CD163 and CD204, the TAM subsets in oral squamous cell carcinoma (OSCC) remain unknown. In this study, we examined the expression and role of TAM subsets in OSCC. Forty-six patients with OSCC were analyzed for expression of TAMs in biopsy samples by immunohistochemistry. We examined TAM subsets and their production of immune suppressive molecules (IL-10 and PD-L1) in peripheral blood mononuclear cells from three OSCC patients by flow cytometry. CD163 was detected around the tumor or connective tissue, while CD204 was detected in/around the tumors. Flow cytometric analysis revealed that CD163(+)CD204(+) TAMs strongly produced IL-10 and PD-L1 in comparison with CD163(+)CD204(−) and CD163(−)CD204(+) TAMs. Furthermore, the number of activated CD3(+) T cells after co-culture with CD163(+)CD204(+) TAMs was significantly lower than that after co-culture with other TAM subsets. In clinical findings, the number of CD163(+)CD204(+) TAMs was negatively correlated with that of CD25(+) cells and 5-year progression-free survival. These results suggest that CD163(+)CD204(+) TAMs possibly play a key role in the invasion and metastasis of OSCC by T-cell regulation via IL-10 and PD-L1 production.",2017 May 11,"['Kubota, Keigo', 'Moriyama, Masafumi', 'Furukawa, Sachiko', 'Rafiul, Haque A. S. M.', 'Maruse, Yasuyuki', 'Jinno, Teppei', 'Tanaka, Akihiko', 'Ohta, Miho', 'Ishiguro, Noriko', 'Yamauchi, Masaaki', 'Sakamoto, Mizuki', 'Maehara, Takashi', 'Hayashida, Jun-Nosuke', 'Kawano, Shintaro', 'Kiyoshima, Tamotsu', 'Nakamura, Seiji']",Sci Rep,,,True
bec70be6631ac68e731b98fed55d2c28af45dc3d,PMC,Fungal lectin MpL enables entry of protein drugs into cancer cells and their subcellular targeting,http://dx.doi.org/10.18632/oncotarget.15849,PMC5432305,28460472,CC BY,"Lectins have been recognized as promising carrier molecules for targeted drug delivery. They specifically bind carbohydrate moieties on cell membranes and trigger cell internalization. Fungal lectin MpL (Macrolepiota procera lectin) does not provoke cancer cell cytotoxicity but is able to bind aminopeptidase N (CD13) and integrin α3β1, two glycoproteins that are overexpressed on the membrane of tumor cells. Upon binding, MpL is endocytosed in a clathrin-dependent manner and accumulates initially in the Golgi apparatus and, finally, in the lysosomes. For effective binding and internalization a functional binding site on the α-repeat is needed. To test the potential of MpL as a carrier for delivering protein drugs to cancer cells we constructed fusion proteins consisting of MpL and the cysteine peptidase inhibitors cystatin C and clitocypin. The fused proteins followed the same endocytic route as the unlinked MpL. Peptidase inhibitor-MpL fusions impaired both the intracellular degradation of extracellular matrix and the invasiveness of cancer cells. MpL is thus shown in vitro to be a lectin that can enable protein drugs to enter cancer cells, enhance their internalization and sort them to lysosomes and the Golgi apparatus.",2017 Mar 2,"['Žurga, Simon', 'Nanut, Milica Perišić', 'Kos, Janko', 'Sabotič, Jerica']",Oncotarget,,,True
06cdbcb7d40c21ce5e10c5a2bc1a1583e66f49d7,PMC,Fungal lectin MpL enables entry of protein drugs into cancer cells and their subcellular targeting,http://dx.doi.org/10.18632/oncotarget.15849,PMC5432305,28460472,CC BY,"Lectins have been recognized as promising carrier molecules for targeted drug delivery. They specifically bind carbohydrate moieties on cell membranes and trigger cell internalization. Fungal lectin MpL (Macrolepiota procera lectin) does not provoke cancer cell cytotoxicity but is able to bind aminopeptidase N (CD13) and integrin α3β1, two glycoproteins that are overexpressed on the membrane of tumor cells. Upon binding, MpL is endocytosed in a clathrin-dependent manner and accumulates initially in the Golgi apparatus and, finally, in the lysosomes. For effective binding and internalization a functional binding site on the α-repeat is needed. To test the potential of MpL as a carrier for delivering protein drugs to cancer cells we constructed fusion proteins consisting of MpL and the cysteine peptidase inhibitors cystatin C and clitocypin. The fused proteins followed the same endocytic route as the unlinked MpL. Peptidase inhibitor-MpL fusions impaired both the intracellular degradation of extracellular matrix and the invasiveness of cancer cells. MpL is thus shown in vitro to be a lectin that can enable protein drugs to enter cancer cells, enhance their internalization and sort them to lysosomes and the Golgi apparatus.",2017 Mar 2,"['Žurga, Simon', 'Nanut, Milica Perišić', 'Kos, Janko', 'Sabotič, Jerica']",Oncotarget,,,False
f79e36092b45aef0e928b577166a4c44198f2825,PMC,Mannose-Binding Lectin (MBL) gene polymorphisms in susceptibility to pulmonary tuberculosis among the Lur population of Lorestan Province of Iran,http://dx.doi.org/10.1016/j.gdata.2017.05.005,PMC5432655,28540182,CC BY,"OBJECTIVE: Tuberculosis (TB) is caused by infection of Mycobacterium tuberculosis. Host genetic variability is an important determinant of the risk of developing TB in humans. Although the association between MBL polymorphisms and TB has been studied in various populations, the results are controversial. The aim of this study was to investigate mannose-binding lectin (MBL) gene polymorphisms with susceptibility to pulmonary tuberculosis (PTB) in a Lur population of Iran. METHODS: In this case-control study, four functional MBL gene polymorphisms (HL, XY, PQ and AB) were genotyped by using PCR Single Strand Conformation Polymorphism (SSCP) technique in a Lur population living in Lorestan Province, consisting of 100 patients with pulmonary tuberculosis (PTB) age and sex matched 100 healthy controls (HCs). Association analyses were performed with the SPSS 21 statistical software. RESULTS: We found that MBL (HH) genotype polymorphism significantly was associated with increased susceptibility to TB (35% in patients vs. 22% in controls, P = 0.0417, OR = 1.909, %95 CI = 1.020–3.573). Additionally, H allele showed a significant association with increased risk of TB (56.5% in patients vs. 46% in controls, P = 0.0357, OR = 1.525, %95 CI = 1.028–2.262). Also, the distribution of L allele in patients was significantly lower frequency in TB patients compared to controls (43.5% vs. 54%, P = 0.0357, OR = 0.656, %95 CI = 0.442–0.973). However, the allelic and genotypic frequencies of AB, XY and PQ polymorphisms were not significantly different between the patients and the controls. We couldn't detect any significant differences between haplotypes among TB patients and healthy controls. CONCLUSIONS: Our findings demonstrated that HH genotype and H allele may increase the susceptibility to pulmonary TB in the Lur population of Iran, although L allele may decrease the susceptibility to pulmonary TB in this population. We suggest that it is necessary to further more studies with larger sample size and other ethnic population.",2017 May 4,"['Amiri, Ali', 'Sabooteh, Toomaj', 'Shahsavar, Farhad', 'Anbari, Khatereh', 'Pouremadi, Flora']",Genom Data,,,False
798d2643cbdd17b150ec009bd4b735e08f8f8e40,PMC,Structure-Based Mutations in the Herpes Simplex Virus 1 Glycoprotein B Ectodomain Arm Impart a Slow-Entry Phenotype,http://dx.doi.org/10.1128/mBio.00614-17,PMC5433099,28512095,CC BY,"Glycoprotein B (gB) is the conserved herpesvirus fusion protein, and it is required for the entry of herpesviruses. The structure of the postfusion conformation of gB has been solved for several herpesviruses; however, the gB prefusion crystal structure and the details of how the protein refolds from a prefusion to a postfusion form to mediate fusion have not been determined. Using structure-based mutagenesis, we previously reported that three mutations (I671A, H681A, and F683A) in the C-terminal arm of the gB ectodomain greatly reduced cell-cell fusion. This fusion deficit could be rescued by the addition of a hyperfusogenic mutation, suggesting that the gB triple mutant was not misfolded. Using a bacterial artificial chromosome (BAC), we constructed two independent herpes simplex virus 1 mutant strains (gB 3A) carrying the three arm mutations. The gB 3A viruses have 200-fold smaller plaques than the wild-type virus and demonstrate remarkably delayed entry into cells. Single-step and multistep growth curves show that gB 3A viruses have delayed replication kinetics. Interestingly, incubation at 40°C promoted the entry of the gB 3A viruses. We propose that the gB 3A viruses’ entry deficit is due to a loss of interactions between residues in the gB C-terminal arm and the coiled-coil core of gB. The results suggest that the triple alanine mutation may destabilize the postfusion gB conformation and/or stabilize the prefusion gB conformation and that exposure to elevated temperatures can overcome the defect in gB 3A viruses.",2017 May 16,"['Fan, Qing', 'Kopp, Sarah J.', 'Connolly, Sarah A.', 'Longnecker, Richard']",mBio,,,True
2d5916f47ca6cc70ac9f50a2cb85be34b6f8e029,PMC,Practical recommendations for strengthening national and regional laboratory networks in Africa in the Global Health Security era,http://dx.doi.org/10.4102/ajlm.v5i3.471,PMC5433810,28879137,CC BY,"The role of national health laboratories in support of public health response has expanded beyond laboratory testing to include a number of other core functions such as emergency response, training and outreach, communications, laboratory-based surveillance and data management. These functions can only be accomplished by an efficient and resilient national laboratory network that includes public health, reference, clinical and other laboratories. It is a primary responsibility of the national health laboratory in the Ministry of Health to develop and maintain the national laboratory network in the country. In this article, we present practical recommendations based on 17 years of network development experience for the development of effective national laboratory networks. These recommendations and examples of current laboratory networks, are provided to facilitate laboratory network development in other states. The development of resilient, integrated laboratory networks will enhance each state’s public health system and is critical to the development of a robust national laboratory response network to meet global health security threats.",2016 Oct 31,"['Best, Michele', 'Sakande, Jean']",Afr J Lab Med,,,True
c32d0c0e6f09f6da1b8d9075733574b26bfec04a,PMC,Geographical distribution of complement receptor type 1 variants and their associated disease risk,http://dx.doi.org/10.1371/journal.pone.0175973,PMC5435133,28520715,CC BY,"BACKGROUND: Pathogens exert selective pressure which may lead to substantial changes in host immune responses. The human complement receptor type 1 (CR1) is an innate immune recognition glycoprotein that regulates the activation of the complement pathway and removes opsonized immune complexes. CR1 genetic variants in exon 29 have been associated with expression levels, C1q or C3b binding and increased susceptibility to several infectious diseases. Five distinct CR1 nucleotide substitutions determine the Knops blood group phenotypes, namely Kn(a/b), McC(a/b), Sl1/Sl2, Sl4/Sl5 and KCAM+/-. METHODS: CR1 variants were genotyped by direct sequencing in a cohort of 441 healthy individuals from Brazil, Vietnam, India, Republic of Congo and Ghana. RESULTS: The distribution of the CR1 alleles, genotypes and haplotypes differed significantly among geographical settings (p≤0.001). CR1 variants rs17047660A/G (McC(a/b)) and rs17047661A/G (Sl1/Sl2) were exclusively observed to be polymorphic in African populations compared to the groups from Asia and South-America, strongly suggesting that these two SNPs may be subjected to selection. This is further substantiated by a high linkage disequilibrium between the two variants in the Congolese and Ghanaian populations. A total of nine CR1 haplotypes were observed. The CR1*AGAATA haplotype was found more frequently among the Brazilian and Vietnamese study groups; the CR1*AGAATG haplotype was frequent in the Indian and Vietnamese populations, while the CR1*AGAGTG haplotype was frequent among Congolese and Ghanaian individuals. CONCLUSION: The African populations included in this study might have a selective advantage conferred to immune genes involved in pathogen recognition and signaling, possibly contributing to disease susceptibility or resistance.",2017 May 17,"['Lucas Sandri, Thaisa', 'Adukpo, Selorme', 'Giang, Dao Phuong', 'Nguetse, Christian N.', 'Antunes Andrade, Fabiana', 'van Tong, Hoang', 'Toan, Nguyen Linh', 'Song, Le Huu', 'Elumalai, Preetham', 'Thangaraj, Kumarasamy', 'Valluri, Vijaya Lakshmi', 'Ntoumi, Francine', 'Meyer, Christian G.', 'Jose de Messias Reason, Iara', 'Kremsner, Peter G.', 'Velavan, Thirumalaisamy P.']",PLoS One,,,True
e69a0c654041707c6ffefca96f14c2f1fe05296c,PMC,Parallel ClickSeq and Nanopore sequencing elucidates the rapid evolution of defective-interfering RNAs in Flock House virus,http://dx.doi.org/10.1371/journal.ppat.1006365,PMC5435362,28475646,CC BY,"Defective-Interfering RNAs (DI-RNAs) have long been known to play an important role in virus replication and transmission. DI-RNAs emerge during virus passaging in both cell-culture and their hosts as a result of non-homologous RNA recombination. However, the principles of DI-RNA emergence and their subsequent evolution have remained elusive. Using a combination of long- and short-read Next-Generation Sequencing, we have characterized the formation of DI-RNAs during serial passaging of Flock House virus (FHV) in cell-culture over a period of 30 days in order to elucidate the pathways and potential mechanisms of DI-RNA emergence and evolution. For short-read RNAseq, we employed ‘ClickSeq’ due to its ability to sensitively and confidently detect RNA recombination events with nucleotide resolution. In parallel, we used the Oxford Nanopore Technologies’s (ONT) MinION to resolve full-length defective and wild-type viral genomes. Together, these accurately resolve both rare and common RNA recombination events, determine the correlation between recombination events, and quantifies the relative abundance of different DI-RNAs throughout passaging. We observe the formation of a diverse pool of defective RNAs at each stage of viral passaging. However, many of these ‘intermediate’ species, while present in early stages of passaging, do not accumulate. After approximately 9 days of passaging we observe the rapid accumulation of DI-RNAs with a correlated reduction in specific infectivity and with the Nanopore data find that DI-RNAs are characterized by multiple RNA recombination events. This suggests that intermediate DI-RNA species are not competitive and that multiple recombination events interact epistatically to confer ‘mature’ DI-RNAs with their selective advantage allowing for their rapid accumulation. Alternatively, it is possible that mature DI-RNA species are generated in a single event involving multiple RNA rearrangements. These insights have important consequences for our understanding of the mechanisms, determinants and limitations in the emergence and evolution of DI-RNAs.",2017 May 5,"['Jaworski, Elizabeth', 'Routh, Andrew']",PLoS Pathog,,,True
ef919d8ada0a198eb02a4989d5860d8c7fa9b273,PMC,Parallel ClickSeq and Nanopore sequencing elucidates the rapid evolution of defective-interfering RNAs in Flock House virus,http://dx.doi.org/10.1371/journal.ppat.1006365,PMC5435362,28475646,CC BY,"Defective-Interfering RNAs (DI-RNAs) have long been known to play an important role in virus replication and transmission. DI-RNAs emerge during virus passaging in both cell-culture and their hosts as a result of non-homologous RNA recombination. However, the principles of DI-RNA emergence and their subsequent evolution have remained elusive. Using a combination of long- and short-read Next-Generation Sequencing, we have characterized the formation of DI-RNAs during serial passaging of Flock House virus (FHV) in cell-culture over a period of 30 days in order to elucidate the pathways and potential mechanisms of DI-RNA emergence and evolution. For short-read RNAseq, we employed ‘ClickSeq’ due to its ability to sensitively and confidently detect RNA recombination events with nucleotide resolution. In parallel, we used the Oxford Nanopore Technologies’s (ONT) MinION to resolve full-length defective and wild-type viral genomes. Together, these accurately resolve both rare and common RNA recombination events, determine the correlation between recombination events, and quantifies the relative abundance of different DI-RNAs throughout passaging. We observe the formation of a diverse pool of defective RNAs at each stage of viral passaging. However, many of these ‘intermediate’ species, while present in early stages of passaging, do not accumulate. After approximately 9 days of passaging we observe the rapid accumulation of DI-RNAs with a correlated reduction in specific infectivity and with the Nanopore data find that DI-RNAs are characterized by multiple RNA recombination events. This suggests that intermediate DI-RNA species are not competitive and that multiple recombination events interact epistatically to confer ‘mature’ DI-RNAs with their selective advantage allowing for their rapid accumulation. Alternatively, it is possible that mature DI-RNA species are generated in a single event involving multiple RNA rearrangements. These insights have important consequences for our understanding of the mechanisms, determinants and limitations in the emergence and evolution of DI-RNAs.",2017 May 5,"['Jaworski, Elizabeth', 'Routh, Andrew']",PLoS Pathog,,,False
ce400824c4b31bdef4a6922f946f441617b9b28b,PMC,Parallel ClickSeq and Nanopore sequencing elucidates the rapid evolution of defective-interfering RNAs in Flock House virus,http://dx.doi.org/10.1371/journal.ppat.1006365,PMC5435362,28475646,CC BY,"Defective-Interfering RNAs (DI-RNAs) have long been known to play an important role in virus replication and transmission. DI-RNAs emerge during virus passaging in both cell-culture and their hosts as a result of non-homologous RNA recombination. However, the principles of DI-RNA emergence and their subsequent evolution have remained elusive. Using a combination of long- and short-read Next-Generation Sequencing, we have characterized the formation of DI-RNAs during serial passaging of Flock House virus (FHV) in cell-culture over a period of 30 days in order to elucidate the pathways and potential mechanisms of DI-RNA emergence and evolution. For short-read RNAseq, we employed ‘ClickSeq’ due to its ability to sensitively and confidently detect RNA recombination events with nucleotide resolution. In parallel, we used the Oxford Nanopore Technologies’s (ONT) MinION to resolve full-length defective and wild-type viral genomes. Together, these accurately resolve both rare and common RNA recombination events, determine the correlation between recombination events, and quantifies the relative abundance of different DI-RNAs throughout passaging. We observe the formation of a diverse pool of defective RNAs at each stage of viral passaging. However, many of these ‘intermediate’ species, while present in early stages of passaging, do not accumulate. After approximately 9 days of passaging we observe the rapid accumulation of DI-RNAs with a correlated reduction in specific infectivity and with the Nanopore data find that DI-RNAs are characterized by multiple RNA recombination events. This suggests that intermediate DI-RNA species are not competitive and that multiple recombination events interact epistatically to confer ‘mature’ DI-RNAs with their selective advantage allowing for their rapid accumulation. Alternatively, it is possible that mature DI-RNA species are generated in a single event involving multiple RNA rearrangements. These insights have important consequences for our understanding of the mechanisms, determinants and limitations in the emergence and evolution of DI-RNAs.",2017 May 5,"['Jaworski, Elizabeth', 'Routh, Andrew']",PLoS Pathog,,,False
10f4c9e6b4982bd1789f15816655beede98eea85,PMC,Parallel ClickSeq and Nanopore sequencing elucidates the rapid evolution of defective-interfering RNAs in Flock House virus,http://dx.doi.org/10.1371/journal.ppat.1006365,PMC5435362,28475646,CC BY,"Defective-Interfering RNAs (DI-RNAs) have long been known to play an important role in virus replication and transmission. DI-RNAs emerge during virus passaging in both cell-culture and their hosts as a result of non-homologous RNA recombination. However, the principles of DI-RNA emergence and their subsequent evolution have remained elusive. Using a combination of long- and short-read Next-Generation Sequencing, we have characterized the formation of DI-RNAs during serial passaging of Flock House virus (FHV) in cell-culture over a period of 30 days in order to elucidate the pathways and potential mechanisms of DI-RNA emergence and evolution. For short-read RNAseq, we employed ‘ClickSeq’ due to its ability to sensitively and confidently detect RNA recombination events with nucleotide resolution. In parallel, we used the Oxford Nanopore Technologies’s (ONT) MinION to resolve full-length defective and wild-type viral genomes. Together, these accurately resolve both rare and common RNA recombination events, determine the correlation between recombination events, and quantifies the relative abundance of different DI-RNAs throughout passaging. We observe the formation of a diverse pool of defective RNAs at each stage of viral passaging. However, many of these ‘intermediate’ species, while present in early stages of passaging, do not accumulate. After approximately 9 days of passaging we observe the rapid accumulation of DI-RNAs with a correlated reduction in specific infectivity and with the Nanopore data find that DI-RNAs are characterized by multiple RNA recombination events. This suggests that intermediate DI-RNA species are not competitive and that multiple recombination events interact epistatically to confer ‘mature’ DI-RNAs with their selective advantage allowing for their rapid accumulation. Alternatively, it is possible that mature DI-RNA species are generated in a single event involving multiple RNA rearrangements. These insights have important consequences for our understanding of the mechanisms, determinants and limitations in the emergence and evolution of DI-RNAs.",2017 May 5,"['Jaworski, Elizabeth', 'Routh, Andrew']",PLoS Pathog,,,False
be330e1288192e8f72bd9beadd9219b970df3639,PMC,Parallel ClickSeq and Nanopore sequencing elucidates the rapid evolution of defective-interfering RNAs in Flock House virus,http://dx.doi.org/10.1371/journal.ppat.1006365,PMC5435362,28475646,CC BY,"Defective-Interfering RNAs (DI-RNAs) have long been known to play an important role in virus replication and transmission. DI-RNAs emerge during virus passaging in both cell-culture and their hosts as a result of non-homologous RNA recombination. However, the principles of DI-RNA emergence and their subsequent evolution have remained elusive. Using a combination of long- and short-read Next-Generation Sequencing, we have characterized the formation of DI-RNAs during serial passaging of Flock House virus (FHV) in cell-culture over a period of 30 days in order to elucidate the pathways and potential mechanisms of DI-RNA emergence and evolution. For short-read RNAseq, we employed ‘ClickSeq’ due to its ability to sensitively and confidently detect RNA recombination events with nucleotide resolution. In parallel, we used the Oxford Nanopore Technologies’s (ONT) MinION to resolve full-length defective and wild-type viral genomes. Together, these accurately resolve both rare and common RNA recombination events, determine the correlation between recombination events, and quantifies the relative abundance of different DI-RNAs throughout passaging. We observe the formation of a diverse pool of defective RNAs at each stage of viral passaging. However, many of these ‘intermediate’ species, while present in early stages of passaging, do not accumulate. After approximately 9 days of passaging we observe the rapid accumulation of DI-RNAs with a correlated reduction in specific infectivity and with the Nanopore data find that DI-RNAs are characterized by multiple RNA recombination events. This suggests that intermediate DI-RNA species are not competitive and that multiple recombination events interact epistatically to confer ‘mature’ DI-RNAs with their selective advantage allowing for their rapid accumulation. Alternatively, it is possible that mature DI-RNA species are generated in a single event involving multiple RNA rearrangements. These insights have important consequences for our understanding of the mechanisms, determinants and limitations in the emergence and evolution of DI-RNAs.",2017 May 5,"['Jaworski, Elizabeth', 'Routh, Andrew']",PLoS Pathog,,,False
1a84330ec88949ccb631781b90bbf38012f33d53,PMC,Parallel ClickSeq and Nanopore sequencing elucidates the rapid evolution of defective-interfering RNAs in Flock House virus,http://dx.doi.org/10.1371/journal.ppat.1006365,PMC5435362,28475646,CC BY,"Defective-Interfering RNAs (DI-RNAs) have long been known to play an important role in virus replication and transmission. DI-RNAs emerge during virus passaging in both cell-culture and their hosts as a result of non-homologous RNA recombination. However, the principles of DI-RNA emergence and their subsequent evolution have remained elusive. Using a combination of long- and short-read Next-Generation Sequencing, we have characterized the formation of DI-RNAs during serial passaging of Flock House virus (FHV) in cell-culture over a period of 30 days in order to elucidate the pathways and potential mechanisms of DI-RNA emergence and evolution. For short-read RNAseq, we employed ‘ClickSeq’ due to its ability to sensitively and confidently detect RNA recombination events with nucleotide resolution. In parallel, we used the Oxford Nanopore Technologies’s (ONT) MinION to resolve full-length defective and wild-type viral genomes. Together, these accurately resolve both rare and common RNA recombination events, determine the correlation between recombination events, and quantifies the relative abundance of different DI-RNAs throughout passaging. We observe the formation of a diverse pool of defective RNAs at each stage of viral passaging. However, many of these ‘intermediate’ species, while present in early stages of passaging, do not accumulate. After approximately 9 days of passaging we observe the rapid accumulation of DI-RNAs with a correlated reduction in specific infectivity and with the Nanopore data find that DI-RNAs are characterized by multiple RNA recombination events. This suggests that intermediate DI-RNA species are not competitive and that multiple recombination events interact epistatically to confer ‘mature’ DI-RNAs with their selective advantage allowing for their rapid accumulation. Alternatively, it is possible that mature DI-RNA species are generated in a single event involving multiple RNA rearrangements. These insights have important consequences for our understanding of the mechanisms, determinants and limitations in the emergence and evolution of DI-RNAs.",2017 May 5,"['Jaworski, Elizabeth', 'Routh, Andrew']",PLoS Pathog,,,False
c5cb7fb393b302569da2df661c860e398de54f7f,PMC,Parallel ClickSeq and Nanopore sequencing elucidates the rapid evolution of defective-interfering RNAs in Flock House virus,http://dx.doi.org/10.1371/journal.ppat.1006365,PMC5435362,28475646,CC BY,"Defective-Interfering RNAs (DI-RNAs) have long been known to play an important role in virus replication and transmission. DI-RNAs emerge during virus passaging in both cell-culture and their hosts as a result of non-homologous RNA recombination. However, the principles of DI-RNA emergence and their subsequent evolution have remained elusive. Using a combination of long- and short-read Next-Generation Sequencing, we have characterized the formation of DI-RNAs during serial passaging of Flock House virus (FHV) in cell-culture over a period of 30 days in order to elucidate the pathways and potential mechanisms of DI-RNA emergence and evolution. For short-read RNAseq, we employed ‘ClickSeq’ due to its ability to sensitively and confidently detect RNA recombination events with nucleotide resolution. In parallel, we used the Oxford Nanopore Technologies’s (ONT) MinION to resolve full-length defective and wild-type viral genomes. Together, these accurately resolve both rare and common RNA recombination events, determine the correlation between recombination events, and quantifies the relative abundance of different DI-RNAs throughout passaging. We observe the formation of a diverse pool of defective RNAs at each stage of viral passaging. However, many of these ‘intermediate’ species, while present in early stages of passaging, do not accumulate. After approximately 9 days of passaging we observe the rapid accumulation of DI-RNAs with a correlated reduction in specific infectivity and with the Nanopore data find that DI-RNAs are characterized by multiple RNA recombination events. This suggests that intermediate DI-RNA species are not competitive and that multiple recombination events interact epistatically to confer ‘mature’ DI-RNAs with their selective advantage allowing for their rapid accumulation. Alternatively, it is possible that mature DI-RNA species are generated in a single event involving multiple RNA rearrangements. These insights have important consequences for our understanding of the mechanisms, determinants and limitations in the emergence and evolution of DI-RNAs.",2017 May 5,"['Jaworski, Elizabeth', 'Routh, Andrew']",PLoS Pathog,,,False
411d0fef061effd665e770d4a9c5db748f1d94c2,PMC,Parallel ClickSeq and Nanopore sequencing elucidates the rapid evolution of defective-interfering RNAs in Flock House virus,http://dx.doi.org/10.1371/journal.ppat.1006365,PMC5435362,28475646,CC BY,"Defective-Interfering RNAs (DI-RNAs) have long been known to play an important role in virus replication and transmission. DI-RNAs emerge during virus passaging in both cell-culture and their hosts as a result of non-homologous RNA recombination. However, the principles of DI-RNA emergence and their subsequent evolution have remained elusive. Using a combination of long- and short-read Next-Generation Sequencing, we have characterized the formation of DI-RNAs during serial passaging of Flock House virus (FHV) in cell-culture over a period of 30 days in order to elucidate the pathways and potential mechanisms of DI-RNA emergence and evolution. For short-read RNAseq, we employed ‘ClickSeq’ due to its ability to sensitively and confidently detect RNA recombination events with nucleotide resolution. In parallel, we used the Oxford Nanopore Technologies’s (ONT) MinION to resolve full-length defective and wild-type viral genomes. Together, these accurately resolve both rare and common RNA recombination events, determine the correlation between recombination events, and quantifies the relative abundance of different DI-RNAs throughout passaging. We observe the formation of a diverse pool of defective RNAs at each stage of viral passaging. However, many of these ‘intermediate’ species, while present in early stages of passaging, do not accumulate. After approximately 9 days of passaging we observe the rapid accumulation of DI-RNAs with a correlated reduction in specific infectivity and with the Nanopore data find that DI-RNAs are characterized by multiple RNA recombination events. This suggests that intermediate DI-RNA species are not competitive and that multiple recombination events interact epistatically to confer ‘mature’ DI-RNAs with their selective advantage allowing for their rapid accumulation. Alternatively, it is possible that mature DI-RNA species are generated in a single event involving multiple RNA rearrangements. These insights have important consequences for our understanding of the mechanisms, determinants and limitations in the emergence and evolution of DI-RNAs.",2017 May 5,"['Jaworski, Elizabeth', 'Routh, Andrew']",PLoS Pathog,,,False
2543902b7ec9b0ae6a2f9ae2b0aa60c96ffed1f4,PMC,Parallel ClickSeq and Nanopore sequencing elucidates the rapid evolution of defective-interfering RNAs in Flock House virus,http://dx.doi.org/10.1371/journal.ppat.1006365,PMC5435362,28475646,CC BY,"Defective-Interfering RNAs (DI-RNAs) have long been known to play an important role in virus replication and transmission. DI-RNAs emerge during virus passaging in both cell-culture and their hosts as a result of non-homologous RNA recombination. However, the principles of DI-RNA emergence and their subsequent evolution have remained elusive. Using a combination of long- and short-read Next-Generation Sequencing, we have characterized the formation of DI-RNAs during serial passaging of Flock House virus (FHV) in cell-culture over a period of 30 days in order to elucidate the pathways and potential mechanisms of DI-RNA emergence and evolution. For short-read RNAseq, we employed ‘ClickSeq’ due to its ability to sensitively and confidently detect RNA recombination events with nucleotide resolution. In parallel, we used the Oxford Nanopore Technologies’s (ONT) MinION to resolve full-length defective and wild-type viral genomes. Together, these accurately resolve both rare and common RNA recombination events, determine the correlation between recombination events, and quantifies the relative abundance of different DI-RNAs throughout passaging. We observe the formation of a diverse pool of defective RNAs at each stage of viral passaging. However, many of these ‘intermediate’ species, while present in early stages of passaging, do not accumulate. After approximately 9 days of passaging we observe the rapid accumulation of DI-RNAs with a correlated reduction in specific infectivity and with the Nanopore data find that DI-RNAs are characterized by multiple RNA recombination events. This suggests that intermediate DI-RNA species are not competitive and that multiple recombination events interact epistatically to confer ‘mature’ DI-RNAs with their selective advantage allowing for their rapid accumulation. Alternatively, it is possible that mature DI-RNA species are generated in a single event involving multiple RNA rearrangements. These insights have important consequences for our understanding of the mechanisms, determinants and limitations in the emergence and evolution of DI-RNAs.",2017 May 5,"['Jaworski, Elizabeth', 'Routh, Andrew']",PLoS Pathog,,,False
6c18f2bf81bf9b00f2a628d540151912b2dfe980,PMC,Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses,http://dx.doi.org/10.1038/s41598-017-02291-1,PMC5435695,28515481,CC BY,"G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5′-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NFκB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5′-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place.",2017 May 17,"['Perrone, Rosalba', 'Lavezzo, Enrico', 'Palù, Giorgio', 'Richter, Sara N.']",Sci Rep,,,True
35173a96f21f1e674e63d473864215d025f76d0d,PMC,Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses,http://dx.doi.org/10.1038/s41598-017-02291-1,PMC5435695,28515481,CC BY,"G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5′-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NFκB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5′-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place.",2017 May 17,"['Perrone, Rosalba', 'Lavezzo, Enrico', 'Palù, Giorgio', 'Richter, Sara N.']",Sci Rep,,,True
2028c33a99d25b4388a27d93fa0d4e2fe2563b54,PMC,Ribonuclease from Bacillus Acts as an Antiviral Agent against Negative- and Positive-Sense Single Stranded Human Respiratory RNA Viruses,http://dx.doi.org/10.1155/2017/5279065,PMC5435908,28546965,CC BY,"Bacillus pumilus ribonuclease (binase) was shown to be a promising antiviral agent in animal models and cell cultures. However, the mode of its antiviral action remains unknown. To assess the binase effect on intracellular viral RNA we have selected single stranded negative- and positive-sense RNA viruses, influenza virus, and rhinovirus, respectively, which annually cause respiratory illnesses and are characterized by high contagious nature, mutation rate, and antigen variability. We have shown that binase exerts an antiviral effect on both viruses at the same concentration, which does not alter the spectrum of A549 cellular proteins and expression of housekeeping genes. The titers of influenza A (H1N1pdm) virus and human rhinovirus serotype 1A were reduced by 40% and 65%, respectively. A preincubation of influenza virus with binase before infection significantly reduced viral titer after single-cycle replication of the virus. Using influenza A virus mini genome system we showed that binase reduced GFP reporter signaling indicating a binase action on the expression of viral mRNA. Binase reduced the level of H1N1pdm viral NP mRNA accumulation in A549 cells by 20%. Since the viral mRNA is a possible target for binase this agent could be potentially applied in the antiviral therapy against both negative- and positive-sense RNA viruses.",2017 May 4,"['Shah Mahmud, Raihan', 'Müller, Christin', 'Romanova, Yulia', 'Mostafa, Ahmed', 'Ulyanova, Vera', 'Pleschka, Stephan', 'Ilinskaya, Olga']",Biomed Res Int,,,True
a735cd10efb7df82d87da350bc33e3ca3acab6ed,PMC,The risk of transmission of a viral haemorrhagic fever infection in a United Kingdom laboratory,http://dx.doi.org/10.1371/journal.pntd.0005358,PMC5436630,28545142,CC BY,,2017 May 18,"['Shorten, Robert J.', 'Wilson-Davies, Eleri']",PLoS Negl Trop Dis,,,True
fc923e6d8eafe27c1056242b741ed1dcc6e574a7,PMC,"NTD policy priorities: Science, values, and agenda setting",http://dx.doi.org/10.1371/journal.pntd.0005431,PMC5436631,28545108,CC BY,,2017 May 18,"['Iltis, Ana S.', 'Matthews, Kirstin R. W.']",PLoS Negl Trop Dis,,,True
7891733fabfa2e1e80fb60263468670d46f95a1c,PMC,"Correction: Serological Evidence of MERS-CoV Antibodies in Dromedary Camels (Camelus dromedaries) in Laikipia County, Kenya",http://dx.doi.org/10.1371/journal.pone.0178310,PMC5436855,28542448,CC BY,,2017 May 18,,PLoS One,,,False
50d0f5fd4187d914ff40cacb3c436edc5b5bcc00,PMC,"Infection-mediated asthma: etiology, mechanisms and treatment options, with focus on Chlamydia pneumoniae and macrolides",http://dx.doi.org/10.1186/s12931-017-0584-z,PMC5437656,28526018,CC BY,"Asthma is a chronic respiratory disease characterized by reversible airway obstruction and airway hyperresponsiveness to non-specific bronchoconstriction agonists as the primary underlying pathophysiology. The worldwide incidence of asthma has increased dramatically in the last 40 years. According to World Health Organization (WHO) estimates, over 300 million children and adults worldwide currently suffer from this incurable disease and 255,000 die from the disease each year. It is now well accepted that asthma is a heterogeneous syndrome and many clinical subtypes have been described. Viral infections such as respiratory syncytial virus (RSV) and human rhinovirus (hRV) have been implicated in asthma exacerbation in children because of their ability to cause severe airway inflammation and wheezing. Infections with atypical bacteria also appear to play a role in the induction and exacerbation of asthma in both children and adults. Recent studies confirm the existence of an infectious asthma etiology mediated by Chlamydia pneumoniae (CP) and possibly by other viral, bacterial and fungal microbes. It is also likely that early-life infections with microbes such as CP could lead to alterations in the lung microbiome that significantly affect asthma risk and treatment outcomes. These infectious microbes may exacerbate the symptoms of established chronic asthma and may even contribute to the initial development of the clinical onset of the disease. It is now becoming more widely accepted that patterns of airway inflammation differ based on the trigger responsible for asthma initiation and exacerbation. Therefore, a better understanding of asthma subtypes is now being explored more aggressively, not only to decipher pathophysiologic mechanisms but also to select treatment and guide prognoses. This review will explore infection-mediated asthma with special emphasis on the protean manifestations of CP lung infection, clinical characteristics of infection-mediated asthma, mechanisms involved and antibiotic treatment outcomes.",2017 May 19,"['Webley, Wilmore C.', 'Hahn, David L.']",Respir Res,,,True
fa6b3fafeedf308826d58db91499b7c09f172310,PMC,Post weaning diarrhea in pigs: risk factors and non-colistin-based control strategies,http://dx.doi.org/10.1186/s13028-017-0299-7,PMC5437690,28526080,CC BY,"Post-weaning diarrhea (PWD) is one of the most serious threats for the swine industry worldwide. It is commonly associated with the proliferation of enterotoxigenic Escherichia coli in the pig intestine. Colistin, a cationic antibiotic, is widely used in swine for the oral treatment of intestinal infections caused by E. coli, and particularly of PWD. However, despite the effectiveness of this antibiotic in the treatment of PWD, several studies have reported high rates of colistin resistant E. coli in swine. Furthermore, this antibiotic is considered of very high importance in humans, being used for the treatment of infections due to multidrug-resistant (MDR) Gram-negative bacteria (GNB). Moreover, the recent discovery of the mcr-1 gene encoding for colistin resistance in Enterobacteriaceae on a conjugative stable plasmid has raised great concern about the possible loss of colistin effectiveness for the treatment of MDR-GNB in humans. Consequently, it has been proposed that the use of colistin in animal production should be considered as a last resort treatment only. Thus, to overcome the economic losses, which would result from the restriction of use of colistin, especially for prophylactic purposes in PWD control, we believe that an understanding of the factors contributing to the development of this disease and the putting in place of practical alternative strategies for the control of PWD in swine is crucial. Such alternatives should improve animal gut health and reduce economic losses in pigs without promoting bacterial resistance. The present review begins with an overview of risk factors of PWD and an update of colistin use in PWD control worldwide in terms of quantities and microbiological outcomes. Subsequently, alternative strategies to the use of colistin for the control of this disease are described and discussed. Finally, a practical approach for the control of PWD in its various phases is proposed.",2017 May 19,"['Rhouma, Mohamed', 'Fairbrother, John Morris', 'Beaudry, Francis', 'Letellier, Ann']",Acta Vet Scand,,,True
a8b614e1c39170f6cab8198aa119e71f28421669,PMC,A scoping review on bio-aerosols in healthcare and the dental environment,http://dx.doi.org/10.1371/journal.pone.0178007,PMC5439730,28531183,CC BY,"BACKGROUND: Bio-aerosols originate from different sources and their potentially pathogenic nature may form a hazard to healthcare workers and patients. So far no extensive review on existing evidence regarding bio-aerosols is available. OBJECTIVES: This study aimed to review evidence on bio-aerosols in healthcare and the dental setting. The objectives were 1) What are the sources that generate bio-aerosols?; 2) What is the microbial load and composition of bio-aerosols and how were they measured?; and 3) What is the hazard posed by pathogenic micro-organisms transported via the aerosol route of transmission? METHODS: Systematic scoping review design. Searched in PubMed and EMBASE from inception to 09-03-2016. References were screened and selected based on abstract and full text according to eligibility criteria. Full text articles were assessed for inclusion and summarized. The results are presented in three separate objectives and summarized for an overview of evidence. RESULTS: The search yielded 5,823 studies, of which 62 were included. Dental hand pieces were found to generate aerosols in the dental settings. Another 30 sources from human activities, interventions and daily cleaning performances in the hospital also generate aerosols. Fifty-five bacterial species, 45 fungi genera and ten viruses were identified in a hospital setting and 16 bacterial and 23 fungal species in the dental environment. Patients with certain risk factors had a higher chance to acquire Legionella in hospitals. Such infections can lead to irreversible septic shock and death. Only a few studies found that bio-aerosol generating procedures resulted in transmission of infectious diseases or allergic reactions. CONCLUSION: Bio-aerosols are generated via multiple sources such as different interventions, instruments and human activity. Bio-aerosols compositions reported are heterogeneous in their microbiological composition dependent on the setting and methodology. Legionella species were found to be a bio-aerosol dependent hazard to elderly and patients with respiratory complaints. But all aerosols can be can be hazardous to both patients and healthcare workers.",2017 May 22,"['Zemouri, Charifa', 'de Soet, Hans', 'Crielaard, Wim', 'Laheij, Alexa']",PLoS One,,,True
3646ec7d036646a765d5afe60f4644346c4a001e,PMC,Lack of inflammatory gene expression in bats: a unique role for a transcription repressor,http://dx.doi.org/10.1038/s41598-017-01513-w,PMC5440382,28533548,CC BY,"In recent years viruses similar to those that appear to cause no overt disease in bats have spilled-over to humans and other species causing serious disease. Since pathology in such diseases is often attributed to an over-active inflammatory response, we tested the hypothesis that bat cells respond to stimulation of their receptors for viral ligands with a strong antiviral response, but unlike in human cells, the inflammatory response is not overtly activated. We compared the response of human and bat cells to poly(I:C), a viral double-stranded RNA surrogate. We measured transcripts for several inflammatory, interferon and interferon stimulated genes using quantitative real-time PCR and observed that human and bat cells both, when stimulated with poly(I:C), contained higher levels of transcripts for interferon beta than unstimulated cells. In contrast, only human cells expressed robust amount of RNA for TNFα, a cell signaling protein involved in systemic inflammation. We examined the bat TNFα promoter and found a potential repressor (c-Rel) binding motif. We demonstrated that c-Rel binds to the putative c-Rel motif in the promoter and knocking down c-Rel transcripts significantly increased basal levels of TNFα transcripts. Our results suggest bats may have a unique mechanism to suppress inflammatory pathology.",2017 May 22,"['Banerjee, Arinjay', 'Rapin, Noreen', 'Bollinger, Trent', 'Misra, Vikram']",Sci Rep,,,True
53324ca7df9751947a7c1b54cf18c65af1c14df8,PMC,Lack of inflammatory gene expression in bats: a unique role for a transcription repressor,http://dx.doi.org/10.1038/s41598-017-01513-w,PMC5440382,28533548,CC BY,"In recent years viruses similar to those that appear to cause no overt disease in bats have spilled-over to humans and other species causing serious disease. Since pathology in such diseases is often attributed to an over-active inflammatory response, we tested the hypothesis that bat cells respond to stimulation of their receptors for viral ligands with a strong antiviral response, but unlike in human cells, the inflammatory response is not overtly activated. We compared the response of human and bat cells to poly(I:C), a viral double-stranded RNA surrogate. We measured transcripts for several inflammatory, interferon and interferon stimulated genes using quantitative real-time PCR and observed that human and bat cells both, when stimulated with poly(I:C), contained higher levels of transcripts for interferon beta than unstimulated cells. In contrast, only human cells expressed robust amount of RNA for TNFα, a cell signaling protein involved in systemic inflammation. We examined the bat TNFα promoter and found a potential repressor (c-Rel) binding motif. We demonstrated that c-Rel binds to the putative c-Rel motif in the promoter and knocking down c-Rel transcripts significantly increased basal levels of TNFα transcripts. Our results suggest bats may have a unique mechanism to suppress inflammatory pathology.",2017 May 22,"['Banerjee, Arinjay', 'Rapin, Noreen', 'Bollinger, Trent', 'Misra, Vikram']",Sci Rep,,,True
7d37dca746114af4879ecb53c1584fb776d748be,PMC,National post-market surveillance assessment of veterinary medicines in Korea during the past decade,http://dx.doi.org/10.1186/s12917-017-1054-z,PMC5441046,28532461,CC BY,"BACKGROUND: Veterinary medicines have been widely used for the prevention and treatment of diseases, growth promotion, and to promote feeding efficacy in livestock. As the veterinary medicine industry has steadily grown, it is crucial to set up a baseline for the quality of medicine as well as the insufficiency or excessiveness of the active ingredients in drug products to ensure the compliance, safety and efficacy of these medicines. Thus, the 10 years data of post-marketing quality control study was summarized to determine the rate and extent of non-compliance of these medicines and to establish baseline data for future quality control measures of veterinary medicine. RESULTS: In this study, 1650 drugs for veterinary use were collected per year from each city and province in Korea and analysed for the quantity of active ingredients according to the “national post-market surveillance (NPMS) system” over the past decade. The NPMS assessment was performed using liquid and gas chromatography, titration, UV/Vis spectrophotometry, and bioassays. A total of 358 cases were deemed noncompliant, with the average noncompliance rate for all medicine types being 2.0%. The average noncompliance rates for antibiotics, biologics and other chemical drugs except antibiotics (OCD) were 1.1%, 1.2%, and 3.0%, respectively. The first leading cause for noncompliant products was insufficient quantity of major ingredients (283 cases), and the second leading cause was the existence of excess amount of active ingredients (60 cases). Tylosin, spiramycin, ampicillin, tetracyclines and penicillins were most frequently found to be noncompliant among antibiotics. Among the OCD, the noncompliance was found commonly in vitamin A. CONCLUSION: The overall trend presented gradually decreasing violation rates, suggesting that the quality of veterinary medicines has improved. Consistent application of the NPMS assessment and the establishment of the Korea Veterinary Good Manufacturing Practice (KVGMP) will help to maintain the good quality of medicine.",2017 May 22,"['Kang, JeongWoo', 'Park, Hae-chul', 'Jang, Yang ho', 'Hossain, Md Akil', 'Jeong, Kyunghun', 'Jeong, Mi young', 'Yun, Seon-Jong', 'Park, Sung-won', 'Kim, Dae gyun', 'Lee, Kwang-jick']",BMC Vet Res,,,True
f4819ac40713b21c42a2cad54d3db7626fdf0956,PMC,Antiviral activity of phenanthrenes from the medicinal plant Bletilla striata against influenza A virus,http://dx.doi.org/10.1186/s12906-017-1780-6,PMC5441103,28532402,CC BY,"BACKGROUND: Influenza represents a serious public health concern. The emergence of resistance to anti-influenza drugs underlines the need to develop new drugs. This study aimed to evaluate the anti-influenza viral activity and possible mechanisms of 12 phenanthrenes from the medicinal plant Bletilla striata (Orchidaceae family). METHODS: Twelve phenanthrenes were isolated and identified from B. striata. Influenza virus A/Sydney/5/97 (H3N2) propagated in embryonated chicken eggs was used. Phenanthrenes mixed with the virus were incubated at 37 °C for 1 h and then inoculated into 9-day-old embryonated chicken eggs via the allantoic route to survey the antiviral activity in vivo. A (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H–tetrazolium) (MTS)-based assay was performed to evaluate the reduction of cytopathic effect induced by H3N2 on Madin-Darby canine kidney (MDCK) cells. The hemagglutination inhibition assay was used to study the blockage of virus receptors by the phenanthrenes, and the neuraminidase (NA) inhibition assay to evaluate the effects of the release of virus. The synthesis of influenza viral matrix protein mRNA in response to compound treatment was measured by real-time polymerase chain reaction. RESULTS: This study showed that phenanthrenes 1, 2, 3, 4, 6, 9, 10, 11, and 12 significantly inhibited the viruses in vivo, with inhibition rates of 20.7, 79.3, 17.2, 34.5, 34.5, 34.5, 44.8, 75.9, and 34.5%, respectively. In MDCK models, the phenanthrenes did not show significant antiviral activity when administered as pretreatment, while phenanthrenes 2, 3, 4, 6, 7 10, and 11 exhibited inhibitory activities as simultaneous treatment with 50% inhibition concentration (IC(50)) ranging from 14.6 ± 2.4 to 43.3 ± 5.3 μM. The IC(50) ranged from 18.4 ± 3.1 to 42.3 ± 3.9 μM in the post-treatment assays. Compounds 1, 3, 4, 6, 10, and 11 exhibited an inhibitory effect on NA; and compounds 2, 3, 4 6, 7, 10, and 11 resulted in the reduced transcription of virus matrix protein mRNA. However, no compound could inhibit hemagglutination by the influenza virus. CONCLUSION: Phenanthrenes from B. striata had strong anti-influenza viral activity in both embryonated eggs and MDCK models, and diphenanthrenes seemed to have stronger inhibition activity compared with monophenanthrenes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12906-017-1780-6) contains supplementary material, which is available to authorized users.",2017 May 22,"['Shi, Ya', 'Zhang, Bing', 'Lu, Yiyu', 'Qian, Chaodong', 'Feng, Yan', 'Fang, Liwei', 'Ding, Zhishan', 'Cheng, Dongqing']",BMC Complement Altern Med,,,True
2fef395624ecfc1747991a5cb4b9b2282aeac208,PMC,Redefining disease emergence to improve prioritization and macro-ecological analyses,http://dx.doi.org/10.1016/j.onehlt.2015.08.001,PMC5441331,28616460,CC BY,"Microbial infections are as old as the hosts they sicken, but interest in the emergence of pathogens and the diseases they cause has been accelerating rapidly. The term ‘emerging infectious disease’ was coined in the mid-1900s to describe changes in disease dynamics in the modern era. Both the term and the phenomena it is meant to characterize have evolved and diversified over time, leading to inconsistencies and confusion. Here, we review the evolution of the term ‘emerging infectious disease’ (EID) in the literature as applied to human hosts. We examine the pathways (e.g., speciation or strain differentiation in the causative agent vs. rapid geographic expansion of an existing pathogen) by which diseases emerge. We propose a new framework for disease and pathogen emergence to improve prioritization. And we illustrate how the operational definition of an EID affects conclusions concerning the pathways by which diseases emerge and the ecological and socioeconomic drivers that elicit emergence. As EIDs appear to be increasing globally, and resources for science level off or decline, the research community is pushed to prioritize its focus on the most threatening diseases, riskiest potential pathogens, and the places they occur. The working definition of emerging infectious diseases and pathogens plays a crucial role in prioritization, but we argue that the current definitions may be impeding these efforts. We propose a new framework for classifying pathogens and diseases as “emerging” that distinguishes EIDs from emerging pathogens and novel potential pathogens. We suggest prioritization of: 1) EIDs for adaptation and mitigation, 2) emerging pathogens for preventive measures, and 3) novel potential pathogens for intensive surveillance.",2015 Aug 11,"['Rosenthal, Samantha R.', 'Ostfeld, Richard S.', 'McGarvey, Stephen T.', 'Lurie, Mark N.', 'Smith, Katherine F.']",One Health,,,False
a7d6aeb7cd27e3f420ae9ca4711ad2ac77651089,PMC,Metagenomic sequencing complements routine diagnostics in identifying viral pathogens in lung transplant recipients with unknown etiology of respiratory infection,http://dx.doi.org/10.1371/journal.pone.0177340,PMC5441588,28542207,CC BY,"BACKGROUND: Lung transplant patients are a vulnerable group of immunosuppressed patients that are prone to frequent respiratory infections. We studied 60 episodes of respiratory symptoms in 71 lung transplant patients. Almost half of these episodes were of unknown infectious etiology despite extensive routine diagnostic testing. METHODS: We re-analyzed respiratory samples of all episodes with undetermined etiology in order to detect potential viral pathogens missed/not accounted for in routine diagnostics. Respiratory samples were enriched for viruses by filtration and nuclease digestion, whole nucleic acids extracted and randomly amplified before high throughput metagenomic virus sequencing. Viruses were identified by a bioinformatic pipeline and confirmed and quantified using specific real-time PCR. RESULTS: In completion of routine diagnostics, we identified and confirmed a viral etiology of infection by our metagenomic approach in four patients (three Rhinovirus A, one Rhinovirus B infection) despite initial negative results in specific multiplex PCR. Notably, the majority of samples were also positive for Torque teno virus (TTV) and Human Herpesvirus 7 (HHV-7). While TTV viral loads increased with immunosuppression in both throat swabs and blood samples, HHV-7 remained at low levels throughout the observation period and was restricted to the respiratory tract. CONCLUSION: This study highlights the potential of metagenomic sequencing for virus diagnostics in cases with previously unknown etiology of infection and in complex diagnostic situations such as in immunocompromised hosts.",2017 May 23,"['Lewandowska, Dagmara W.', 'Schreiber, Peter W.', 'Schuurmans, Macé M.', 'Ruehe, Bettina', 'Zagordi, Osvaldo', 'Bayard, Cornelia', 'Greiner, Michael', 'Geissberger, Fabienne D.', 'Capaul, Riccarda', 'Zbinden, Andrea', 'Böni, Jürg', 'Benden, Christian', 'Mueller, Nicolas J.', 'Trkola, Alexandra', 'Huber, Michael']",PLoS One,,,True
a945fe15ef46edadf3f4712668dfc7ee8e5c821d,PMC,SARS and hospital priority setting: a qualitative case study and evaluation,http://dx.doi.org/10.1186/1472-6963-4-36,PMC544195,15606924,CC BY,"BACKGROUND: Priority setting is one of the most difficult issues facing hospitals because of funding restrictions and changing patient need. A deadly communicable disease outbreak, such as the Severe Acute Respiratory Syndrome (SARS) in Toronto in 2003, amplifies the difficulties of hospital priority setting. The purpose of this study is to describe and evaluate priority setting in a hospital in response to SARS using the ethical framework 'accountability for reasonableness'. METHODS: This study was conducted at a large tertiary hospital in Toronto, Canada. There were two data sources: 1) over 200 key documents (e.g. emails, bulletins), and 2) 35 interviews with key informants. Analysis used a modified thematic technique in three phases: open coding, axial coding, and evaluation. RESULTS: Participants described the types of priority setting decisions, the decision making process and the reasoning used. Although the hospital leadership made an effort to meet the conditions of 'accountability for reasonableness', they acknowledged that the decision making was not ideal. We described good practices and opportunities for improvement. CONCLUSIONS: 'Accountability for reasonableness' is a framework that can be used to guide fair priority setting in health care organizations, such as hospitals. In the midst of a crisis such as SARS where guidance is incomplete, consequences uncertain, and information constantly changing, where hour-by-hour decisions involve life and death, fairness is more important rather than less.",2004 Dec 19,"['Bell, Jennifer AH', 'Hyland, Sylvia', 'DePellegrin, Tania', 'Upshur, Ross EG', 'Bernstein, Mark', 'Martin, Douglas K']",BMC Health Serv Res,,,True
eaea0b941204c8ad04aa8e2842013a41e2f87622,PMC,Targeted Enrichment for Pathogen Detection and Characterization in Three Felid Species,http://dx.doi.org/10.1128/JCM.01463-16,PMC5442522,28330894,CC BY,"Traditional diagnostic assays often lack sensitivity and can be difficult to multiplex across many pathogens. Next-generation sequencing (NGS) can overcome some of these problems but has limited application in the detection of low-copy-number pathogens in complex samples. Targeted genome capture (TGC) utilizes oligonucleotide probes to enrich specific nucleic acids in heterogeneous extracts and can therefore increase the proportion of NGS reads for low-abundance targets. While earlier studies have demonstrated the utility of this technology for detection of novel pathogens in human clinical samples, the capacity and practicality of TGC-NGS in a veterinary diagnostic setting have not yet been evaluated. Here we report the use of TGC-NGS assays for the detection and characterization of diverse feline pathogen taxa. We detected 31 pathogens comprising nine pathogen taxa in 28 felid samples analyzed. This included 20 pathogens detected via traditional PCR and 11 additional pathogens that had not been previously detected in the same samples. Most of the pathogens detected were sequenced at sufficient breadth and depth to confidently classify them at the species or subspecies level. Target nucleic acids were enriched from a low of 58-fold to 56 million-fold relative to host nucleic acids. Despite the promising performance of these assays, a number of pathogens detected by conventional PCR or serology were not isolated by TGC-NGS, suggesting that further validation is required before this technology can be used in lieu of quality-controlled standard assays. We conclude that TGC-NGS offers great potential as a broad multiplex pathogen characterization assay in veterinary diagnostic and research settings.",2017 Jun 23,"['Lee, Justin S.', 'Mackie, Ryan S.', 'Harrison, Thomas', 'Shariat, Basir', 'Kind, Trey', 'Kehl, Timo', 'Löchelt, Martin', 'Boucher, Christina', 'VandeWoude, Sue']",J Clin Microbiol,,,False
186d00062af3e7276319079bb16f4a00fa30a670,PMC,Targeted Enrichment for Pathogen Detection and Characterization in Three Felid Species,http://dx.doi.org/10.1128/JCM.01463-16,PMC5442522,28330894,CC BY,"Traditional diagnostic assays often lack sensitivity and can be difficult to multiplex across many pathogens. Next-generation sequencing (NGS) can overcome some of these problems but has limited application in the detection of low-copy-number pathogens in complex samples. Targeted genome capture (TGC) utilizes oligonucleotide probes to enrich specific nucleic acids in heterogeneous extracts and can therefore increase the proportion of NGS reads for low-abundance targets. While earlier studies have demonstrated the utility of this technology for detection of novel pathogens in human clinical samples, the capacity and practicality of TGC-NGS in a veterinary diagnostic setting have not yet been evaluated. Here we report the use of TGC-NGS assays for the detection and characterization of diverse feline pathogen taxa. We detected 31 pathogens comprising nine pathogen taxa in 28 felid samples analyzed. This included 20 pathogens detected via traditional PCR and 11 additional pathogens that had not been previously detected in the same samples. Most of the pathogens detected were sequenced at sufficient breadth and depth to confidently classify them at the species or subspecies level. Target nucleic acids were enriched from a low of 58-fold to 56 million-fold relative to host nucleic acids. Despite the promising performance of these assays, a number of pathogens detected by conventional PCR or serology were not isolated by TGC-NGS, suggesting that further validation is required before this technology can be used in lieu of quality-controlled standard assays. We conclude that TGC-NGS offers great potential as a broad multiplex pathogen characterization assay in veterinary diagnostic and research settings.",2017 Jun 23,"['Lee, Justin S.', 'Mackie, Ryan S.', 'Harrison, Thomas', 'Shariat, Basir', 'Kind, Trey', 'Kehl, Timo', 'Löchelt, Martin', 'Boucher, Christina', 'VandeWoude, Sue']",J Clin Microbiol,,,False
ced400d9d754e83891f4bc5b6ea39845fe076c92,PMC,Targeted Enrichment for Pathogen Detection and Characterization in Three Felid Species,http://dx.doi.org/10.1128/JCM.01463-16,PMC5442522,28330894,CC BY,"Traditional diagnostic assays often lack sensitivity and can be difficult to multiplex across many pathogens. Next-generation sequencing (NGS) can overcome some of these problems but has limited application in the detection of low-copy-number pathogens in complex samples. Targeted genome capture (TGC) utilizes oligonucleotide probes to enrich specific nucleic acids in heterogeneous extracts and can therefore increase the proportion of NGS reads for low-abundance targets. While earlier studies have demonstrated the utility of this technology for detection of novel pathogens in human clinical samples, the capacity and practicality of TGC-NGS in a veterinary diagnostic setting have not yet been evaluated. Here we report the use of TGC-NGS assays for the detection and characterization of diverse feline pathogen taxa. We detected 31 pathogens comprising nine pathogen taxa in 28 felid samples analyzed. This included 20 pathogens detected via traditional PCR and 11 additional pathogens that had not been previously detected in the same samples. Most of the pathogens detected were sequenced at sufficient breadth and depth to confidently classify them at the species or subspecies level. Target nucleic acids were enriched from a low of 58-fold to 56 million-fold relative to host nucleic acids. Despite the promising performance of these assays, a number of pathogens detected by conventional PCR or serology were not isolated by TGC-NGS, suggesting that further validation is required before this technology can be used in lieu of quality-controlled standard assays. We conclude that TGC-NGS offers great potential as a broad multiplex pathogen characterization assay in veterinary diagnostic and research settings.",2017 Jun 23,"['Lee, Justin S.', 'Mackie, Ryan S.', 'Harrison, Thomas', 'Shariat, Basir', 'Kind, Trey', 'Kehl, Timo', 'Löchelt, Martin', 'Boucher, Christina', 'VandeWoude, Sue']",J Clin Microbiol,,,True
5645bc52d703b021b132a5bb5ca1702809db4cb5,PMC,Comparison of ePlex Respiratory Pathogen Panel with Laboratory-Developed Real-Time PCR Assays for Detection of Respiratory Pathogens,http://dx.doi.org/10.1128/JCM.00221-17,PMC5442551,28404682,CC BY,"Infections of the respiratory tract can be caused by a diversity of pathogens, both viral and bacterial. Rapid microbiological diagnosis ensures appropriate antimicrobial therapy as well as effective implementation of isolation precautions. The ePlex respiratory pathogen panel (RP panel) is a novel molecular biology-based assay, developed by GenMark Diagnostics, Inc. (Carlsbad, CA), to be performed within a single cartridge for the diagnosis of 25 respiratory pathogens (viral and bacterial). The objective of this study was to compare the performance of the RP panel with those of laboratory-developed real-time PCR assays, using a variety of previously collected clinical respiratory specimens. A total of 343 clinical specimens as well as 29 external quality assessment (EQA) specimens and 2 different Middle East respiratory syndrome coronavirus isolates have been assessed in this study. The RP panel showed an agreement of 97.4% with the real-time PCR assay regarding 464 pathogens found in the clinical specimens. All pathogens present in clinical samples and EQA samples with a threshold cycle (C(T)) value of <30 were detected correctly using the RP panel. The RP panel detected 17 additional pathogens, 7 of which could be confirmed by discrepant testing. In conclusion, this study shows excellent performance of the RP panel in comparison to real-time PCR assays for the detection of respiratory pathogens. The ePlex system provided a large amount of useful diagnostic data within a short time frame, with minimal hands-on time, and can therefore potentially be used for rapid diagnostic sample-to-answer testing, in either a laboratory or a decentralized setting.",2017 Jun 23,"['Nijhuis, R. H. T.', 'Guerendiain, D.', 'Claas, E. C. J.', 'Templeton, K. E.']",J Clin Microbiol,,,True
0771924722e625f8b49b2686a41e899954a962d0,PMC,Human Lung Spheroids as In Vitro Niches of Lung Progenitor Cells with Distinctive Paracrine and Plasticity Properties,http://dx.doi.org/10.5966/sctm.2015-0374,PMC5442776,28297570,CC BY,"Basic and translational research on lung biology has discovered multiple progenitor cell types, specialized or facultative, responsible for turnover, renewal, and repair. Isolation of populations of resident lung progenitor cells (LPCs) has been described by multiple protocols, and some have been successfully applied to healthy human lung tissue. We aimed at understanding how different cell culture conditions may affect, in vitro, the phenotype of LPCs to create an ideal niche‐like microenvironment. The influence of different substrates (i.e., fibronectin, gelatin, laminin) and the impact of a three‐dimensional/two‐dimensional (3D/2D) culture switch on the biology of LPCs isolated as lung spheroids (LSs) from normal adult human lung biopsy specimens were investigated. We applied a spheroid culture system as the selective/inductive step for progenitor cell culture, as described in many biological systems. The data showed a niche‐like proepithelial microenvironment inside the LS, highly sensitive to the 3D culture system and significantly affecting the phenotype of adult LPCs more than culture substrate. LSs favor epithelial phenotypes and LPC maintenance and contain cells more responsive to specific commitment stimuli than 2D monolayer cultures, while secreting a distinctive set of paracrine factors. We have shown for the first time, to our knowledge, how culture as 3D LSs can affect LPC epithelial phenotype and produce strong paracrine signals with a distinctive secretomic profile compared with 2D monolayer conditions. These findings suggest novel approaches to maintain ex vivo LPCs for basic and translational studies. Stem Cells Translational Medicine 2017;6:767–777",2017 Mar 22,"['Chimenti, Isotta', 'Pagano, Francesca', 'Angelini, Francesco', 'Siciliano, Camilla', 'Mangino, Giorgio', 'Picchio, Vittorio', 'De Falco, Elena', 'Peruzzi, Mariangela', 'Carnevale, Roberto', 'Ibrahim, Mohsen', 'Biondi‐Zoccai, Giuseppe', 'Messina, Elisa', 'Frati, Giacomo']",Stem Cells Transl Med,,,True
5c197df5eefa068596dfa256ad9a3c71415727a5,PMC,Human Lung Spheroids as In Vitro Niches of Lung Progenitor Cells with Distinctive Paracrine and Plasticity Properties,http://dx.doi.org/10.5966/sctm.2015-0374,PMC5442776,28297570,CC BY,"Basic and translational research on lung biology has discovered multiple progenitor cell types, specialized or facultative, responsible for turnover, renewal, and repair. Isolation of populations of resident lung progenitor cells (LPCs) has been described by multiple protocols, and some have been successfully applied to healthy human lung tissue. We aimed at understanding how different cell culture conditions may affect, in vitro, the phenotype of LPCs to create an ideal niche‐like microenvironment. The influence of different substrates (i.e., fibronectin, gelatin, laminin) and the impact of a three‐dimensional/two‐dimensional (3D/2D) culture switch on the biology of LPCs isolated as lung spheroids (LSs) from normal adult human lung biopsy specimens were investigated. We applied a spheroid culture system as the selective/inductive step for progenitor cell culture, as described in many biological systems. The data showed a niche‐like proepithelial microenvironment inside the LS, highly sensitive to the 3D culture system and significantly affecting the phenotype of adult LPCs more than culture substrate. LSs favor epithelial phenotypes and LPC maintenance and contain cells more responsive to specific commitment stimuli than 2D monolayer cultures, while secreting a distinctive set of paracrine factors. We have shown for the first time, to our knowledge, how culture as 3D LSs can affect LPC epithelial phenotype and produce strong paracrine signals with a distinctive secretomic profile compared with 2D monolayer conditions. These findings suggest novel approaches to maintain ex vivo LPCs for basic and translational studies. Stem Cells Translational Medicine 2017;6:767–777",2017 Mar 22,"['Chimenti, Isotta', 'Pagano, Francesca', 'Angelini, Francesco', 'Siciliano, Camilla', 'Mangino, Giorgio', 'Picchio, Vittorio', 'De Falco, Elena', 'Peruzzi, Mariangela', 'Carnevale, Roberto', 'Ibrahim, Mohsen', 'Biondi‐Zoccai, Giuseppe', 'Messina, Elisa', 'Frati, Giacomo']",Stem Cells Transl Med,,,False
f5ea98913fa93c8a3fd33c7fd296f07934069299,PMC,Meeting Report VLPNPV: Session 10: Rapid total particle quantification,http://dx.doi.org/10.4161/21645515.2014.986994,PMC5443056,25511481,CC BY,,2014 Dec 15,"Artinger, Michael",Hum Vaccin Immunother,,,False
eb88125e0384bc94499e00b623b18a7d033d0c1a,PMC,"Potential disease transmission from wild geese and swans to livestock, poultry and humans: a review of the scientific literature from a One Health perspective",http://dx.doi.org/10.1080/20008686.2017.1300450,PMC5443079,28567210,CC BY,"There are more herbivorous waterfowl (swans and geese) close to humans, livestock and poultry than ever before. This creates widespread conflict with agriculture and other human interests, but also debate about the role of swans and geese as potential vectors of disease of relevance for human and animal health. Using a One Health perspective, we provide the first comprehensive review of the scientific literature about the most relevant viral, bacterial, and unicellular pathogens occurring in wild geese and swans. Research thus far suggests that these birds may play a role in transmission of avian influenza virus, Salmonella, Campylobacter, and antibiotic resistance. On the other hand, at present there is no evidence that geese and swans play a role in transmission of Newcastle disease, duck plague, West Nile virus, Vibrio, Yersinia, Clostridium, Chlamydophila, and Borrelia. Finally, based on present knowledge it is not possible to say if geese and swans play a role in transmission of Escherichia coli, Pasteurella, Helicobacter, Brachyspira, Cryptosporidium, Giardia, and Microsporidia. This is largely due to changes in classification and taxonomy, rapid development of identification methods and lack of knowledge about host specificity. Previous research tends to overrate the role of geese and swans as disease vectors; we do not find any evidence that they are significant transmitters to humans or livestock of any of the pathogens considered in this review. Nevertheless, it is wise to keep poultry and livestock separated from small volume waters used by many wild waterfowl, but there is no need to discourage livestock grazing in nature reserves or pastures where geese and swans are present. Under some circumstances it is warranted to discourage swans and geese from using wastewater ponds, drinking water reservoirs, and public beaches. Intensified screening of swans and geese for AIV, West Nile virus and anatid herpesvirus is warranted.",2017 Apr 10,"['Elmberg, Johan', 'Berg, Charlotte', 'Lerner, Henrik', 'Waldenström, Jonas', 'Hessel, Rebecca']",Infect Ecol Epidemiol,,,True
2142f50e9a7ace971bc142fe4067a52c91b7af28,PMC,Environmental persistence of porcine coronaviruses in feed and feed ingredients,http://dx.doi.org/10.1371/journal.pone.0178094,PMC5443540,28542235,CC BY,"Porcine Epidemic Diarrhea Virus (PEDV), Porcine Delta Corona Virus (PDCoV), and Transmissible Gastroenteritis Virus (TGEV) are major threats to swine health and contaminated feed plays a role in virus transmission. The objective of our study was to characterize inactivation of PEDV, PDCoV, and TGEV in various feed ingredient matrices. Samples of complete feed, spray dried porcine plasma, meat meal, meat and bone meal, blood meal, corn, soybean meal, and corn dried distillers grains with solubles were weighed (5 g/sample) into scintillation vials and inoculated with 1 mL of PEDV, PDCoV, or TGEV. Samples were incubated at room temperature for up to 56 days. Aliquots were removed at various time points followed by preparing serial 10-fold dilutions and inoculating in cell cultures to determine the amount of surviving virus. Inactivation kinetics were determined using the Weibull model, which estimates a delta value indicating the time necessary to reduce virus concentration by 1 log. Delta values of various ingredients were compared and analyzed as to their nutrient composition. Soybean meal had the greatest delta value (7.50 days) for PEDV (P < 0.06) as compared with all other ingredients. High delta values (P < 0.001) were observed in soybean meal for PDCoV (42.04 days) and TGEV (42.00 days). There was a moderate correlation between moisture content and the delta value for PDCoV (r = 0.49, P = 0.01) and TGEV (r = 0.41, P = 0.02). There was also a moderate negative correlation between TGEV survival and ether extract content (r = -0.51, P = 0.01). In conclusion, these results indicate that the first log reduction of PDCoV and TGEV takes the greatest amount of time in soybean meal. In addition to this, moisture and ether content appear to be an important determinant of virus survival in feed ingredients.",2017 May 24,"['Trudeau, Michaela P.', 'Verma, Harsha', 'Sampedro, Fernando', 'Urriola, Pedro E.', 'Shurson, Gerald C.', 'Goyal, Sagar M.']",PLoS One,,,True
9e04a35a1a1baaf00a3745918df2aecc93e1ef74,PMC,A core extended naphtalene diimide G-quadruplex ligand potently inhibits herpes simplex virus 1 replication,http://dx.doi.org/10.1038/s41598-017-02667-3,PMC5443766,28539620,CC BY,"G-quadruplexes (G4s) are nucleic acids secondary structures, epigenetic regulators in cells and viruses. In herpes simplex virus 1 (HSV-1)-infected cells, G4s are massively present during viral replication. We here aimed at investigating the possibility to target the HSV-1 G4s by a core extended naphtalene diimide (c-exNDI) G4 ligand. Biophysical and biomolecular analysis proved that c-exNDI stabilized the HSV-1 G4s in a concentration dependent manner. In MS competition assays, c-exNDI preferentially recognized HSV-1 G4s over cellular telomeric G4s, the most represented G4s within cells; other less abundant cellular G4s were also recognized. Treatment of HSV-1 infected cells with c-exNDI at low nanomolar concentrations induced significant virus inhibition with no cytotoxicity. The mechanism of action was ascribed to G4-mediated inhibition of viral DNA replication, with consequent impairment of viral genes transcription. Our data suggest that the observed potent antiviral activity and low cytotoxicity mainly depend on a combination of c-exNDI affinity for HSV-1 G4s and their massive presence during infection. HSV-1 G4s may thus represent new effective antiviral targets: the fact that no current antiherpetic drug exploits them and their presence at the viral genome, responsible for both active and latent HSV infections, makes them particularly attracting.",2017 May 24,"['Callegaro, Sara', 'Perrone, Rosalba', 'Scalabrin, Matteo', 'Doria, Filippo', 'Palù, Giorgio', 'Richter, Sara N.']",Sci Rep,,,False
56b2d409fd554bd2694eb7d938fd44fc282fd484,PMC,A core extended naphtalene diimide G-quadruplex ligand potently inhibits herpes simplex virus 1 replication,http://dx.doi.org/10.1038/s41598-017-02667-3,PMC5443766,28539620,CC BY,"G-quadruplexes (G4s) are nucleic acids secondary structures, epigenetic regulators in cells and viruses. In herpes simplex virus 1 (HSV-1)-infected cells, G4s are massively present during viral replication. We here aimed at investigating the possibility to target the HSV-1 G4s by a core extended naphtalene diimide (c-exNDI) G4 ligand. Biophysical and biomolecular analysis proved that c-exNDI stabilized the HSV-1 G4s in a concentration dependent manner. In MS competition assays, c-exNDI preferentially recognized HSV-1 G4s over cellular telomeric G4s, the most represented G4s within cells; other less abundant cellular G4s were also recognized. Treatment of HSV-1 infected cells with c-exNDI at low nanomolar concentrations induced significant virus inhibition with no cytotoxicity. The mechanism of action was ascribed to G4-mediated inhibition of viral DNA replication, with consequent impairment of viral genes transcription. Our data suggest that the observed potent antiviral activity and low cytotoxicity mainly depend on a combination of c-exNDI affinity for HSV-1 G4s and their massive presence during infection. HSV-1 G4s may thus represent new effective antiviral targets: the fact that no current antiherpetic drug exploits them and their presence at the viral genome, responsible for both active and latent HSV infections, makes them particularly attracting.",2017 May 24,"['Callegaro, Sara', 'Perrone, Rosalba', 'Scalabrin, Matteo', 'Doria, Filippo', 'Palù, Giorgio', 'Richter, Sara N.']",Sci Rep,,,True
ee3cc22161595e877450737882a52950fd179672,PMC,Multimodal Imaging in an Unusual Cluster of Multiple Evanescent White Dot Syndrome,http://dx.doi.org/10.1155/2017/7535320,PMC5444036,28584665,CC BY,"OBJECTIVE: To describe an unusual cluster of multiple evanescent white dot syndrome (MEWDS) encountered within a 3-month period. METHODS: This retrospective observation study is comprised of seven patients who presented with MEWDS in a 3-month period in central Israel. Data were collected from patients' medical records on clinical, multimodal imaging, and viral serology findings. RESULTS: Six women and one man of mean age 31.5 ± 7.2 years. Three reported a precedent viral infection. All had unilateral decreased vision. Funduscopy revealed foveal granularity. MAIN IMAGING FINDINGS: Hyperfluorescent spots on blue autofluorescence (BAF), hypofluorescent spots on indocyanine green angiography, dark lesions on infrared photos, and ellipsoid zone irregularities on spectral domain optical coherence tomography (SD-OCT). Resolution of the spots on BAF correlated with anatomic (SD-OCT) and visual recovery. OCT angiography performed following the convalescence stage demonstrated intact retinal and choroidal flow. Serologic findings were inconclusive. CONCLUSION: We report a unique cluster of MEWDS patients presented in a short period of time. SD-OCT findings of ellipsoid zone disruption in combination with other multimodal imaging modalities are outlined meticulously. Recognizing these imaging features along with high index of clinical suspicion is important for the diagnosis of MEWDS. Serologic testing might be considered in future patients.",2017 May 11,"['Gal-Or, Orly', 'Priel, Ethan', 'Rosenblatt, Irit', 'Shulman, Shiri', 'Kramer, Michal']",J Ophthalmol,,,True
9182c40a4be4e5849c1bcf4a0fbe20e5ca86e168,PMC,Russian–United States vaccine science diplomacy: Preserving the legacy,http://dx.doi.org/10.1371/journal.pntd.0005320,PMC5444589,28542186,CC BY,,2017 May 25,"Hotez, Peter J.",PLoS Negl Trop Dis,,,True
e7f04672caa0b2d82df86553cdc266ff9ddda6fd,PMC,Russian–United States vaccine science diplomacy: Preserving the legacy,http://dx.doi.org/10.1371/journal.pntd.0005320,PMC5444589,28542186,CC BY,,2017 May 25,"Hotez, Peter J.",PLoS Negl Trop Dis,,,True
14f427656a9898ce76f31cb012f258a9aa6d1ce3,PMC,Establishment a real-time reverse transcription PCR based on host biomarkers for the detection of the subclinical cases of Mycobacterium avium subsp. paratuberculosis,http://dx.doi.org/10.1371/journal.pone.0178336,PMC5444815,28542507,CC BY,"Bovine paratuberculosis (PTB) is a chronic enteric inflammatory disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP) that causes large economic losses in the dairy industry. Spread of PTB is mainly provoked by a long subclinical stage during which MAP is shed into the environment with feces; accordingly, detection of subclinical animals is very important to its control. However, current diagnostic methods are not suitable for detection of subclinical animals. Therefore, the current study was conducted to develop a diagnostic method for analysis of the expression of genes of prognostic potential biomarker candidates in the whole blood of cattle naturally infected with MAP. Real-time PCR with nine potential biomarker candidates was developed for the diagnosis of MAP subclinical infection. Animals were divided into four groups based on fecal MAP PCR and serum ELISA. Eight genes (Timp1, Hp, Serpine1, Tfrc, Mmp9, Defb1, Defb10, and S100a8) were up-regulated in MAP-infected cattle (p <0.05). Moreover, ROC analysis revealed that eight genes (Timp1, Hp, Serpine1, Tfrc, Mmp9, Defb1, Defb10, and S100a8) showed fair diagnostic performance (AUC≥0.8). Four biomarkers (Timp1, S100a8, Defb1, and Defb10) showed the highest diagnostic accuracy in the PCR positive and ELISA negative group (PN group) and three biomarkers (Tfrc, Hp, and Serpine1) showed the highest diagnostic accuracy in the PCR negative and ELISA positive group (NP group). Moreover, three biomarkers (S100a8, Hp, and Defb10) were considered the most reliable for the PCR positive and ELISA positive group (PP group). Taken together, our data suggest that real-time PCR based on eight biomarkers (Timp1, Hp, Serpine1, Tfrc, Mmp9, Defb1, Defb10, and S100a8) might be useful for diagnosis of JD, including subclinical stage cases.",2017 May 25,"['Park, Hyun-Eui', 'Park, Hong-Tae', 'Jung, Young Hoon', 'Yoo, Han Sang']",PLoS One,,,True
678116d4f14c2470ef9dbde987d11b2e9b679865,PMC,Antigen-Sparing and Enhanced Efficacy of Multivalent Vaccines Adjuvanted with Immunopotentiators in Chickens,http://dx.doi.org/10.3389/fmicb.2017.00927,PMC5445108,28603519,CC BY,"We previously described that immunopotentiators, CVCVA5, increased the efficacy of H5 and H9 subtype avian influenza vaccines in chickens, ducks, and geese. In this study, we further investigated the effects of the CVCVA5 for improving the efficacy of other univalent or multivalent inactivated vaccines. The immune response administrated with half-dose of monovalent vaccine plus CVCVA5 were higher than those of one dose of monovalent vaccine without immunopotentiators as measured by levels of antibodies from serum, tears and bronchoalveolar lavage fluids, and cytokines of IFNγ and IL-4 from serum. Vaccines included the univalent vaccine of Newcastle Disease virus (ND), Egg Drop Syndrome virus (EDS), Infectious Bronchitis virus (IB), and Infectious Bursal Disease virus (IBD). The CVCVA5 also improved the immune response of both ND and IBD vaccines with less dosage. The sterile protective immunity was monitored with one- or a half-dose of adjuvanted ND vaccine or one dose of adjuvanted IBD vaccine, respectively. The improved immune efficacy was observed in a half-dose of adjuvanted bivalent vaccines compared to one dose of vaccines without CVCVA5 as measured by the antibody levels, including bivalent vaccine of ND-H9, ND-IB, and ND-IBD. The CVCVA5 also boosted the immune efficacy of the tetravalent vaccine (ND-IB-EDS-H9). A half-dose of adjuvanted commercial vaccine or 75% antigen-sparing adjuvanted vaccine elicited similar antibody levels to those of one dose non-adjuvanted commercial vaccines. The CVCVA5 improved the effect of a booster vaccination as measured by the antibody levels against H5 or H9 virus antigens, in which chickens primed with the adjuvanted ND-IB vaccines given a booster with H5–H9 bivalent vaccines without CVCVA5 using 5-day intervals. The inflammatory response may contribute to these additional effects by increasing the levels of IFNγ and IL-4 after the injection of the adjuvanted ND-IB vaccines. Results indicated that the CVCVA5 improved the serum and mucosal antibody levels, cytokine levels of the chickens given the univalent vaccine, and also improved serum antibody titers in bivalent and tetravalent vaccines. This has a potential as an improve vaccine.",2017 May 26,"['Wu, Peipei', 'Lu, Jihu', 'Feng, Lei', 'Wu, Hongzhuan', 'Zhang, Xuehua', 'Mei, Mei', 'Hou, Jibo', 'Liu, Xiufan', 'Tang, Yinghua']",Front Microbiol,,,True
15253c08a446817c195eab73473fc2f215528705,PMC,Roles of LncRNAs in Viral Infections,http://dx.doi.org/10.3389/fcimb.2017.00205,PMC5445353,28603696,CC BY,"Many proteins and signaling pathways participate in anti-viral host responses. Long non-coding RNAs (lncRNAs), a subset of non-coding RNAs greater than 200 nucleotides in length, have been recently described as critical regulators in viral infections. Accumulating research indicates that lncRNAs are important in the development and progression of infectious diseases. LncRNAs are not only involved in anti-viral responses, but in many different virus-host interactions, some of which may be beneficial to the virus. Here we review the current knowledge regarding host and viral lncRNAs and their roles in viral infections. In addition, the potential of using lncRNAs as diagnostic biomarkers is discussed.",2017 May 26,"['Liu, Weiwei', 'Ding, Chan']",Front Cell Infect Microbiol,,,True
7c8670a19ee742ba73283dedb53245f0489b74b7,PMC,Novel algorithm for accelerated electroanatomic mapping and prediction of earliest activation of focal cardiac arrhythmias using mathematical optimization,http://dx.doi.org/10.1016/j.hrthm.2017.03.001,PMC5446561,28279745,CC BY,"BACKGROUND: Premature beats (PBs) are a common finding in patients suffering from structural heart disease, but they can also be present in healthy individuals. Catheter ablation represents a suitable therapeutic approach. However, the exact localization of the origin can be challenging, especially in cases of low PB burden during the procedure. OBJECTIVE: The aim of this study was to develop an automated mapping algorithm on the basis of the hypothesis that mathematical optimization would significantly accelerate the localization of earliest activation. METHODS: The algorithm is based on iterative regression analyses. When acquiring local activation times (LATs) within a 3-dimensional anatomic map of the corresponding heart chamber, this algorithm is able to identify that exact position where a next LAT measurement adds maximum information about the predicted site of origin. Furthermore, on the basis of the acquired LAT measurements, the algorithm is able to predict earliest activation with high accuracy. RESULTS: A systematic retrospective analysis of the mapping performance comparing the operator with simulated search processes by the algorithm within 17 electroanatomic maps of focal spreading arrhythmias revealed a highly significant reduction of necessary LAT measurements from 55 ± 8.8 to 10 ± 0.51 (n = 17; P < .0001). CONCLUSION: On the basis of mathematical optimization, we developed an algorithm that is able to reduce the number of LAT measurements necessary to locate the site of earliest activation. This algorithm might significantly accelerate the mapping procedure by guiding the operator to the optimal position for the next LAT measurement. Furthermore, the algorithm would be able to predict the site of origin with high accuracy early during the mapping procedure.",2017 Jun,"['Weber, Tobias', 'Katus, Hugo A.', 'Sager, Sebastian', 'Scholz, Eberhard P.']",Heart Rhythm,,,False
dea03e84033c9b7f87fc9b280ce9f806e78bbaee,PMC,"Detection of alpha- and betacoronaviruses in rodents from Yunnan, China",http://dx.doi.org/10.1186/s12985-017-0766-9,PMC5446729,28549438,CC BY,"BACKGROUND: Rodents represent the most diverse mammals on the planet and are important reservoirs of human pathogens. Coronaviruses infect various animals, but to date, relatively few coronaviruses have been identified in rodents worldwide. The evolution and ecology of coronaviruses in rodent have not been fully investigated. RESULTS: In this study, we collected 177 intestinal samples from thress species of rodents in Jianchuan County, Yunnan Province, China. Alphacoronavirus and betacoronavirus were detected in 23 rodent samples from three species, namely Apodemus chevrieri (21/98), Eothenomys fidelis (1/62), and Apodemus ilex (1/17). We further characterized the full-length genome of an alphacoronavirus from the A. chevrieri rat and named it as AcCoV-JC34. The AcCoV-JC34 genome was 27,649 nucleotides long and showed a structure similar to the HKU2 bat coronavirus. Comparing the normal transcription regulatory sequence (TRS), 3 variant TRS sequences upstream the spike (S), ORF3, and ORF8 genes were found in the genome of AcCoV-JC34. In the conserved replicase domains, AcCoV-JC34 was most closely related to Rattus norvegicus coronavirus LNRV but diverged from other alphacoronaviruses, indicating that AcCoV-JC34 and LNRV may represent a novel alphacoronavirus species. However, the S and nucleocapsid proteins showed low similarity to those of LRNV, with 66.5 and 77.4% identities, respectively. Phylogenetic analysis revealed that the S genes of AcCoV-JC34, LRNV, and HKU2 formed a distinct lineage with all known coronaviruses. CONCLUSIONS: Both alphacoronaviruses and betacoronaviruses were detected in Apodemus chevrieri in the Yunnan Province of China, indicating that Apodemus chevrieri is an important host for coronavirus. Several new features were identified in the genome of an Apodemus chevrieri coronavirus. The phylogenetic distance to other coronaviruses suggests a variable origin and evolutionary route of the S genes of AcCoV-JC34, LRNV, and HKU2. These results indicate that the diversity of rodent coronaviruses is much higher than previously expected. Further surveillance and functional studies of these coronaviruses will help to better understand the importance of rodent as host for coronaviruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-017-0766-9) contains supplementary material, which is available to authorized users.",2017 May 26,"['Ge, Xing-Yi', 'Yang, Wei-Hong', 'Zhou, Ji-Hua', 'Li, Bei', 'Zhang, Wei', 'Shi, Zheng-Li', 'Zhang, Yun-Zhi']",Virol J,,,False
519bd743684c847c5a54c416f00c79c74068c6dd,PMC,"Detection of alpha- and betacoronaviruses in rodents from Yunnan, China",http://dx.doi.org/10.1186/s12985-017-0766-9,PMC5446729,28549438,CC BY,"BACKGROUND: Rodents represent the most diverse mammals on the planet and are important reservoirs of human pathogens. Coronaviruses infect various animals, but to date, relatively few coronaviruses have been identified in rodents worldwide. The evolution and ecology of coronaviruses in rodent have not been fully investigated. RESULTS: In this study, we collected 177 intestinal samples from thress species of rodents in Jianchuan County, Yunnan Province, China. Alphacoronavirus and betacoronavirus were detected in 23 rodent samples from three species, namely Apodemus chevrieri (21/98), Eothenomys fidelis (1/62), and Apodemus ilex (1/17). We further characterized the full-length genome of an alphacoronavirus from the A. chevrieri rat and named it as AcCoV-JC34. The AcCoV-JC34 genome was 27,649 nucleotides long and showed a structure similar to the HKU2 bat coronavirus. Comparing the normal transcription regulatory sequence (TRS), 3 variant TRS sequences upstream the spike (S), ORF3, and ORF8 genes were found in the genome of AcCoV-JC34. In the conserved replicase domains, AcCoV-JC34 was most closely related to Rattus norvegicus coronavirus LNRV but diverged from other alphacoronaviruses, indicating that AcCoV-JC34 and LNRV may represent a novel alphacoronavirus species. However, the S and nucleocapsid proteins showed low similarity to those of LRNV, with 66.5 and 77.4% identities, respectively. Phylogenetic analysis revealed that the S genes of AcCoV-JC34, LRNV, and HKU2 formed a distinct lineage with all known coronaviruses. CONCLUSIONS: Both alphacoronaviruses and betacoronaviruses were detected in Apodemus chevrieri in the Yunnan Province of China, indicating that Apodemus chevrieri is an important host for coronavirus. Several new features were identified in the genome of an Apodemus chevrieri coronavirus. The phylogenetic distance to other coronaviruses suggests a variable origin and evolutionary route of the S genes of AcCoV-JC34, LRNV, and HKU2. These results indicate that the diversity of rodent coronaviruses is much higher than previously expected. Further surveillance and functional studies of these coronaviruses will help to better understand the importance of rodent as host for coronaviruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-017-0766-9) contains supplementary material, which is available to authorized users.",2017 May 26,"['Ge, Xing-Yi', 'Yang, Wei-Hong', 'Zhou, Ji-Hua', 'Li, Bei', 'Zhang, Wei', 'Shi, Zheng-Li', 'Zhang, Yun-Zhi']",Virol J,,,True
a714dc2983f4139a10c0222d8816654277e72965,PMC,Attitudes of consumers and live-poultry workers to central slaughtering in controlling H7N9: a cross-sectional study,http://dx.doi.org/10.1186/s12889-017-4374-9,PMC5446744,28549473,CC BY,"BACKGROUND: Guangdong Province in the Pearl River Delta of Southeast China is among the areas in the country with the highest rates of avian flu cases. In order to control the outbreak of human-infected H7N9 cases, Guangdong launched a new policy on the central slaughtering of live poultry in 2015. This study aims to evaluate attitudes of consumers and live-poultry workers toward the policy. The live-poultry workers consisted of two sub-groups: live-poultry traders and poultry farm workers. METHODS: Consumers and live-poultry workers from Guangdong were enrolled by stratified multi-stage random sampling. Online and field surveys were conducted to investigate participants’ attitudes on policy implementation. Questionnaires were developed to quantify participant demographics, to collect information about attitudes toward the policy, and to identify influential factors of policy acceptability. Proportional odds logistics regression was used in the univariate and multivariate analyses. A total of 1449 consumers, 181 live-poultry traders, and 114 poultry farm workers completed the study. RESULTS: Policy acceptability percentages among consumers, live-poultry traders, and poultry farm workers were 57.1, 37.9, and 62.6%, respectively. Logistics regression shows that consumers tended not to support the policy if they were males, if they were concerned with the food safety of chilled products, and if they preferred purchasing live poultry. Live-poultry traders tended not to support if they were subsidized by the government, if they were males, if they experienced a drop in trading volume, and if they were unclear whether avian flu was a preventable disease. Finally, poultry farm workers tended not to support if they experienced a drop in trading volume, if they operated a poultry farm on a small to medium scale, and if they experienced inconvenience in their work due to the policy. CONCLUSIONS: The study reveals a substantial refusal or slowness to accept the policy. Failure to accept the policy results from varying reasons. Among consumers, concern about food safety and dietary preference are two major causes of disapproval. Policy acceptability among live-poultry workers diverges within the two sub-groups. While a large percentage of poultry farm workers accept the policy, the drop in trading and an insufficient subsidy hamper acceptance by live-poultry traders. We recommend that policy-makers promote health education and alleviate the policy impact on trading with a reformed subsidy policy to increase acceptability. These findings are crucial for the prevention of human-infected H7N9 cases in Guangdong. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-017-4374-9) contains supplementary material, which is available to authorized users.",2017 May 26,"['Lin, Xiao', 'Zhang, Dingmei', 'Wang, Xinwei', 'Huang, Yun', 'Du, Zhicheng', 'Zou, Yaming', 'Lu, Jiahai', 'Hao, Yuantao']",BMC Public Health,,,True
9fd85ed07e4b503e9ddb2f5dd4c94f0a12ba4361,PMC,Bronchiectasis in Children: Current Concepts in Immunology and Microbiology,http://dx.doi.org/10.3389/fped.2017.00123,PMC5447051,28611970,CC BY,"Bronchiectasis is a complex chronic respiratory condition traditionally characterized by chronic infection, airway inflammation, and progressive decline in lung function. Early diagnosis and intensive treatment protocols can stabilize or even improve the clinical prognosis of children with bronchiectasis. However, understanding the host immunologic mechanisms that contribute to recurrent infection and prolonged inflammation has been identified as an important area of research that would contribute substantially to effective prevention strategies for children at risk of bronchiectasis. This review will focus on the current understanding of the role of the host immune response and important pathogens in the pathogenesis of bronchiectasis (not associated with cystic fibrosis) in children.",2017 May 29,"['Pizzutto, Susan J.', 'Hare, Kim M.', 'Upham, John W.']",Front Pediatr,,,True
8d1ae8aa93426fbd79c96483ab83e0841ff8893c,PMC,Is Higher Viral Load in the Upper Respiratory Tract Associated With Severe Pneumonia? Findings From the PERCH Study,http://dx.doi.org/10.1093/cid/cix148,PMC5447843,28575373,CC BY,"BACKGROUND. The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral load could provide evidence of causality of pneumonia, we compared viral load in the URT of children with World Health Organization–defined severe and very severe pneumonia and age-matched community controls. METHODS. In the 9 developing country sites, nasopharyngeal/oropharyngeal swabs from children with and without pneumonia were tested using quantitative real-time polymerase chain reaction for 17 viruses. The association of viral load with case status was evaluated using logistic regression. Receiver operating characteristic (ROC) curves were constructed to determine optimal discriminatory viral load cutoffs. Viral load density distributions were plotted. RESULTS. The mean viral load was higher in cases than controls for 7 viruses. However, there was substantial overlap in viral load distribution of cases and controls for all viruses. ROC curves to determine the optimal viral load cutoff produced an area under the curve of <0.80 for all viruses, suggesting poor to fair discrimination between cases and controls. Fatal and very severe pneumonia cases did not have higher viral load than less severe cases for most viruses. CONCLUSIONS. Although we found higher viral loads among pneumonia cases than controls for some viruses, the utility in using viral load of URT specimens to define viral pneumonia was equivocal. Our analysis was limited by lack of a gold standard for viral pneumonia.",2017 Jun 15,"['Feikin, Daniel R.', 'Fu, Wei', 'Park, Daniel E.', 'Shi, Qiyuan', 'Higdon, Melissa M.', 'Baggett, Henry C.', 'Brooks, W. Abdullah', 'Deloria Knoll, Maria', 'Hammitt, Laura L.', 'Howie, Stephen R. C.', 'Kotloff, Karen L.', 'Levine, Orin S.', 'Madhi, Shabir A.', 'Scott, J. Anthony G.', 'Thea, Donald M.', 'Adrian, Peter V.', 'Antonio, Martin', 'Awori, Juliet O.', 'Baillie, Vicky L.', 'DeLuca, Andrea N.', 'Driscoll, Amanda J.', 'Ebruke, Bernard E.', 'Goswami, Doli', 'Karron, Ruth A.', 'Li, Mengying', 'Morpeth, Susan C.', 'Mwaba, John', 'Mwansa, James', 'Prosperi, Christine', 'Sawatwong, Pongpun', 'Sow, Samba O.', 'Tapia, Milagritos D.', 'Whistler, Toni', 'Zaman, Khalequ', 'Zeger, Scott L.', 'O’ Brien, Katherine L.', 'Murdoch, David R.', None]",Clin Infect Dis,,,True
82a002a89d1e48ac636317b09d01d9d7da18113e,PMC,Limited Utility of Polymerase Chain Reaction in Induced Sputum Specimens for Determining the Causes of Childhood Pneumonia in Resource-Poor Settings: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study,http://dx.doi.org/10.1093/cid/cix098,PMC5447848,28575363,CC BY,"BACKGROUND. Sputum examination can be useful in diagnosing the cause of pneumonia in adults but is less well established in children. We sought to assess the diagnostic utility of polymerase chain reaction (PCR) for detection of respiratory viruses and bacteria in induced sputum (IS) specimens from children hospitalized with severe or very severe pneumonia. METHODS. Among children aged 1–59 months, we compared organism detection by multiplex PCR in IS and nasopharyngeal/oropharyngeal (NP/OP) specimens. To assess whether organism presence or density in IS specimens was associated with chest radiographic evidence of pneumonia (radiographic pneumonia), we compared prevalence and density in IS specimens from children with radiographic pneumonia and children with suspected pneumonia but without chest radiographic changes or clinical or laboratory findings suggestive of pneumonia (nonpneumonia group). RESULTS. Among 4232 cases with World Health Organization–defined severe or very severe pneumonia, we identified 1935 (45.7%) with radiographic pneumonia and 573 (13.5%) with nonpneumonia. The organism detection yield was marginally improved with IS specimens (96.2% vs 92.4% for NP/OP specimens for all viruses combined [P = .41]; 96.9% vs 93.3% for all bacteria combined [P = .01]). After accounting for presence in NP/OP specimens, no organism was detected more frequently in the IS specimens from the radiographic pneumonia compared with the nonpneumonia cases. Among high-quality IS specimens, there were no statistically significant differences in organism density, except with cytomegalovirus, for which there was a higher quantity in the IS specimens from cases with radiographic pneumonia compared with the nonpneumonia cases (median cycle threshold value, 27.9 vs 28.5, respectively; P = .01). CONCLUSIONS. Using advanced molecular methods with IS specimens provided little additional diagnostic information beyond that obtained with NP/OP swab specimens.",2017 Jun 15,"['Thea, Donald M.', 'Seidenberg, Phil', 'Park, Daniel E.', 'Mwananyanda, Lawrence', 'Fu, Wei', 'Shi, Qiyuan', 'Baggett, Henry C.', 'Brooks, W. Abdullah', 'Feikin, Daniel R.', 'Howie, Stephen R.C.', 'Knoll, Maria Deloria', 'Kotloff, Karen L.', 'Levine, Orin S.', 'Madhi, Shabir A.', 'O’Brien, Katherine L.', 'Scott, J. Anthony G.', 'Antonio, Martin', 'Awori, Juliet O.', 'Baillie, Vicky L.', 'DeLuca, Andrea N.', 'Driscoll, Amanda J.', 'Higdon, Melissa M.', 'Hossain, Lokman', 'Jahan, Yasmin', 'Karron, Ruth A.', 'Kazungu, Sidi', 'Li, Mengying', 'Moore, David P.', 'Morpeth, Susan C.', 'Ofordile, Ogochukwu', 'Prosperi, Christine', 'Sangwichian, Ornuma', 'Sawatwong, Pongpun', 'Sylla, Mamadou', 'Tapia, Milagritos D.', 'Zeger, Scott L.', 'Murdoch, David R.', 'Hammitt, Laura L.', None]",Clin Infect Dis,,,True
27785fc9727a9c538b279d2c940f72ab5b9a3423,PMC,Limited Utility of Polymerase Chain Reaction in Induced Sputum Specimens for Determining the Causes of Childhood Pneumonia in Resource-Poor Settings: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study,http://dx.doi.org/10.1093/cid/cix098,PMC5447848,28575363,CC BY,"BACKGROUND. Sputum examination can be useful in diagnosing the cause of pneumonia in adults but is less well established in children. We sought to assess the diagnostic utility of polymerase chain reaction (PCR) for detection of respiratory viruses and bacteria in induced sputum (IS) specimens from children hospitalized with severe or very severe pneumonia. METHODS. Among children aged 1–59 months, we compared organism detection by multiplex PCR in IS and nasopharyngeal/oropharyngeal (NP/OP) specimens. To assess whether organism presence or density in IS specimens was associated with chest radiographic evidence of pneumonia (radiographic pneumonia), we compared prevalence and density in IS specimens from children with radiographic pneumonia and children with suspected pneumonia but without chest radiographic changes or clinical or laboratory findings suggestive of pneumonia (nonpneumonia group). RESULTS. Among 4232 cases with World Health Organization–defined severe or very severe pneumonia, we identified 1935 (45.7%) with radiographic pneumonia and 573 (13.5%) with nonpneumonia. The organism detection yield was marginally improved with IS specimens (96.2% vs 92.4% for NP/OP specimens for all viruses combined [P = .41]; 96.9% vs 93.3% for all bacteria combined [P = .01]). After accounting for presence in NP/OP specimens, no organism was detected more frequently in the IS specimens from the radiographic pneumonia compared with the nonpneumonia cases. Among high-quality IS specimens, there were no statistically significant differences in organism density, except with cytomegalovirus, for which there was a higher quantity in the IS specimens from cases with radiographic pneumonia compared with the nonpneumonia cases (median cycle threshold value, 27.9 vs 28.5, respectively; P = .01). CONCLUSIONS. Using advanced molecular methods with IS specimens provided little additional diagnostic information beyond that obtained with NP/OP swab specimens.",2017 Jun 15,"['Thea, Donald M.', 'Seidenberg, Phil', 'Park, Daniel E.', 'Mwananyanda, Lawrence', 'Fu, Wei', 'Shi, Qiyuan', 'Baggett, Henry C.', 'Brooks, W. Abdullah', 'Feikin, Daniel R.', 'Howie, Stephen R.C.', 'Knoll, Maria Deloria', 'Kotloff, Karen L.', 'Levine, Orin S.', 'Madhi, Shabir A.', 'O’Brien, Katherine L.', 'Scott, J. Anthony G.', 'Antonio, Martin', 'Awori, Juliet O.', 'Baillie, Vicky L.', 'DeLuca, Andrea N.', 'Driscoll, Amanda J.', 'Higdon, Melissa M.', 'Hossain, Lokman', 'Jahan, Yasmin', 'Karron, Ruth A.', 'Kazungu, Sidi', 'Li, Mengying', 'Moore, David P.', 'Morpeth, Susan C.', 'Ofordile, Ogochukwu', 'Prosperi, Christine', 'Sangwichian, Ornuma', 'Sawatwong, Pongpun', 'Sylla, Mamadou', 'Tapia, Milagritos D.', 'Zeger, Scott L.', 'Murdoch, David R.', 'Hammitt, Laura L.', None]",Clin Infect Dis,,,True
8276d64861e070805d56b292163da25b0240253f,PMC,Bayesian Estimation of Pneumonia Etiology: Epidemiologic Considerations and Applications to the Pneumonia Etiology Research for Child Health Study,http://dx.doi.org/10.1093/cid/cix144,PMC5447849,28575370,CC BY,"In pneumonia, specimens are rarely obtained directly from the infection site, the lung, so the pathogen causing infection is determined indirectly from multiple tests on peripheral clinical specimens, which may have imperfect and uncertain sensitivity and specificity, so inference about the cause is complex. Analytic approaches have included expert review of case-only results, case–control logistic regression, latent class analysis, and attributable fraction, but each has serious limitations and none naturally integrate multiple test results. The Pneumonia Etiology Research for Child Health (PERCH) study required an analytic solution appropriate for a case–control design that could incorporate evidence from multiple specimens from cases and controls and that accounted for measurement error. We describe a Bayesian integrated approach we developed that combined and extended elements of attributable fraction and latent class analyses to meet some of these challenges and illustrate the advantage it confers regarding the challenges identified for other methods.",2017 Jun 15,"['Deloria Knoll, Maria', 'Fu, Wei', 'Shi, Qiyuan', 'Prosperi, Christine', 'Wu, Zhenke', 'Hammitt, Laura L.', 'Feikin, Daniel R.', 'Baggett, Henry C.', 'Howie, Stephen R.C.', 'Scott, J. Anthony G.', 'Murdoch, David R.', 'Madhi, Shabir A.', 'Thea, Donald M.', 'Brooks, W. Abdullah', 'Kotloff, Karen L.', 'Li, Mengying', 'Park, Daniel E.', 'Lin, Wenyi', 'Levine, Orin S.', 'O’Brien, Katherine L.', 'Zeger, Scott L.']",Clin Infect Dis,,,True
11dfd91790da005937371365098de726ddfaec98,PMC,Bayesian Estimation of Pneumonia Etiology: Epidemiologic Considerations and Applications to the Pneumonia Etiology Research for Child Health Study,http://dx.doi.org/10.1093/cid/cix144,PMC5447849,28575370,CC BY,"In pneumonia, specimens are rarely obtained directly from the infection site, the lung, so the pathogen causing infection is determined indirectly from multiple tests on peripheral clinical specimens, which may have imperfect and uncertain sensitivity and specificity, so inference about the cause is complex. Analytic approaches have included expert review of case-only results, case–control logistic regression, latent class analysis, and attributable fraction, but each has serious limitations and none naturally integrate multiple test results. The Pneumonia Etiology Research for Child Health (PERCH) study required an analytic solution appropriate for a case–control design that could incorporate evidence from multiple specimens from cases and controls and that accounted for measurement error. We describe a Bayesian integrated approach we developed that combined and extended elements of attributable fraction and latent class analyses to meet some of these challenges and illustrate the advantage it confers regarding the challenges identified for other methods.",2017 Jun 15,"['Deloria Knoll, Maria', 'Fu, Wei', 'Shi, Qiyuan', 'Prosperi, Christine', 'Wu, Zhenke', 'Hammitt, Laura L.', 'Feikin, Daniel R.', 'Baggett, Henry C.', 'Howie, Stephen R.C.', 'Scott, J. Anthony G.', 'Murdoch, David R.', 'Madhi, Shabir A.', 'Thea, Donald M.', 'Brooks, W. Abdullah', 'Kotloff, Karen L.', 'Li, Mengying', 'Park, Daniel E.', 'Lin, Wenyi', 'Levine, Orin S.', 'O’Brien, Katherine L.', 'Zeger, Scott L.']",Clin Infect Dis,,,True
b4523d37bd98ceef10d57d2e5a11abb5cd068832,PMC,"Radix Bupleuri: A Review of Traditional Uses, Botany, Phytochemistry, Pharmacology, and Toxicology",http://dx.doi.org/10.1155/2017/7597596,PMC5448051,28593176,CC BY,"Radix Bupleuri (Chaihu) has been used as a traditional medicine for more than 2000 years in China, Japan, Korea, and other Asian countries. Phytochemical studies demonstrated that this plant contains essential oils, triterpenoid saponins, polyacetylenes, flavonoids, lignans, fatty acids, and sterols. Crude extracts and pure compounds isolated from Radix Bupleuri exhibited various biological activities, such as anti-inflammatory, anticancer, antipyretic, antimicrobial, antiviral, hepatoprotective, neuroprotective, and immunomodulatory effects. However, Radix Bupleuri could also lead to hepatotoxicity, particularly in high doses and with long-term use. Pharmacokinetic studies have demonstrated that the major bioactive compounds (saikosaponins a, b(2), c, and d) were absorbed rapidly in rats after oral administration of the extract of Radix Bupleuri. This review aims to comprehensively summarize the traditional uses, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics of Radix Bupleuri reported to date with an emphasis on its biological properties and mechanisms of action.",2017 May 16,"['Yang, Fude', 'Dong, Xiaoxv', 'Yin, Xingbin', 'Wang, Wenping', 'You, Longtai', 'Ni, Jian']",Biomed Res Int,,,True
505f56215f18a8d205927dd48898f22a336b5b4b,PMC,The involvement of survival signaling pathways in rubella-virus induced apoptosis,http://dx.doi.org/10.1186/1743-422X-2-1,PMC544859,15631631,CC BY,"Rubella virus (RV) causes severe congenital defects when acquired during the first trimester of pregnancy. RV cytopathic effect has been shown to be due to caspase-dependent apoptosis in a number of susceptible cell lines, and it has been suggested that this apoptotic induction could be a causal factor in the development of such defects. Often the outcome of apoptotic stimuli is dependent on apoptotic, proliferative and survival signaling mechanisms in the cell. Therefore we investigated the role of phosphoinositide 3-kinase (PI3K)-Akt survival signaling and Ras-Raf-MEK-ERK proliferative signaling during RV-induced apoptosis in RK13 cells. Increasing levels of phosphorylated ERK, Akt and GSK3β were detected from 24–96 hours post-infection, concomitant with RV-induced apoptotic signals. Inhibition of PI3K-Akt signaling reduced cell viability, and increased the speed and magnitude of RV-induced apoptosis, suggesting that this pathway contributes to cell survival during RV infection. In contrast, inhibition of the Ras-Raf-MEK-ERK pathway impaired RV replication and growth and reduced RV-induced apoptosis, suggesting that the normal cellular growth is required for efficient virus production.",2005 Jan 4,"['Cooray, Samantha', 'Jin, Li', 'Best, Jennifer M']",Virol J,,,True
91b3ef8e5827c66d841a773d4d1190b6007f4735,PMC,Gene expression patterns induced at different stages of rhinovirus infection in human alveolar epithelial cells,http://dx.doi.org/10.1371/journal.pone.0176947,PMC5448745,28558071,CC BY,"Human rhinovirus (HRV) is the common virus that causes acute respiratory infection (ARI) and is frequently associated with lower respiratory tract infections (LRTIs). We aimed to investigate whether HRV infection induces a specific gene expression pattern in airway epithelial cells. Alveolar epithelial cell monolayers were infected with HRV species B (HRV-B). RNA was extracted from both supernatants and infected monolayer cells at 6, 12, 24 and 48 hours post infection (hpi) and transcriptional profile was analyzed using Affymetrix GeneChip and the results were subsequently validated using quantitative Real-time PCR method. HRV-B infects alveolar epithelial cells which supports implication of the virus with LRTIs. In total 991 genes were found differentially expressed during the course of infection. Of these, 459 genes were up-regulated whereas 532 genes were down-regulated. Differential gene expression at 6 hpi (187 genes up-regulated vs. 156 down-regulated) were significantly represented by gene ontologies related to the chemokines and inflammatory molecules indicating characteristic of viral infection. The 75 up-regulated genes surpassed the down-regulated genes (35) at 12 hpi and their enriched ontologies fell into discrete functional entities such as regulation of apoptosis, anti-apoptosis, and wound healing. At later time points of 24 and 48 hpi, predominated down-regulated genes were enriched for extracellular matrix proteins and airway remodeling events. Our data provides a comprehensive image of host response to HRV infection. The study suggests the underlying molecular regulatory networks genes which might be involved in pathogenicity of the HRV-B and potential targets for further validations and development of effective treatment.",2017 May 30,"['Reza Etemadi, Mohammad', 'Ling, King-Hwa', 'Zainal Abidin, Shahidee', 'Chee, Hui-Yee', 'Sekawi, Zamberi']",PLoS One,,,True
83b05e8afa6cbe7a68170ee155f7eca37c91d51f,PMC,Bioinformatic mapping of AlkB homology domains in viruses,http://dx.doi.org/10.1186/1471-2164-6-1,PMC544882,15627404,CC BY,"BACKGROUND: AlkB-like proteins are members of the 2-oxoglutarate- and Fe(II)-dependent oxygenase superfamily. In Escherichia coli the protein protects RNA and DNA against damage from methylating agents. 1-methyladenine and 3-methylcytosine are repaired by oxidative demethylation and direct reversal of the methylated base back to its unmethylated form. Genes for AlkB homologues are widespread in nature, and Eukaryotes often have several genes coding for AlkB-like proteins. Similar domains have also been observed in certain plant viruses. The function of the viral domain is unknown, but it has been suggested that it may be involved in protecting the virus against the post-transcriptional gene silencing (PTGS) system found in plants. We wanted to do a phylogenomic mapping of viral AlkB-like domains as a basis for analysing functional aspects of these domains, because this could have some relevance for understanding possible alternative roles of AlkB homologues e.g. in Eukaryotes. RESULTS: Profile-based searches of protein sequence libraries showed that AlkB-like domains are found in at least 22 different single-stranded RNA positive-strand plant viruses, but mainly in a subgroup of the Flexiviridae family. Sequence analysis indicated that the AlkB domains probably are functionally conserved, and that they most likely have been integrated relatively recently into several viral genomes at geographically distinct locations. This pattern seems to be more consistent with increased environmental pressure, e.g. from methylating pesticides, than with interaction with the PTGS system. CONCLUSIONS: The AlkB domain found in viral genomes is most likely a conventional DNA/RNA repair domain that protects the viral RNA genome against methylating compounds from the environment.",2005 Jan 3,"['Bratlie, Marit S', 'Drabløs, Finn']",BMC Genomics,,,True
1b40a9366c5ef214054c87a1b9ee90a2225e947f,PMC,Bioinformatic mapping of AlkB homology domains in viruses,http://dx.doi.org/10.1186/1471-2164-6-1,PMC544882,15627404,CC BY,"BACKGROUND: AlkB-like proteins are members of the 2-oxoglutarate- and Fe(II)-dependent oxygenase superfamily. In Escherichia coli the protein protects RNA and DNA against damage from methylating agents. 1-methyladenine and 3-methylcytosine are repaired by oxidative demethylation and direct reversal of the methylated base back to its unmethylated form. Genes for AlkB homologues are widespread in nature, and Eukaryotes often have several genes coding for AlkB-like proteins. Similar domains have also been observed in certain plant viruses. The function of the viral domain is unknown, but it has been suggested that it may be involved in protecting the virus against the post-transcriptional gene silencing (PTGS) system found in plants. We wanted to do a phylogenomic mapping of viral AlkB-like domains as a basis for analysing functional aspects of these domains, because this could have some relevance for understanding possible alternative roles of AlkB homologues e.g. in Eukaryotes. RESULTS: Profile-based searches of protein sequence libraries showed that AlkB-like domains are found in at least 22 different single-stranded RNA positive-strand plant viruses, but mainly in a subgroup of the Flexiviridae family. Sequence analysis indicated that the AlkB domains probably are functionally conserved, and that they most likely have been integrated relatively recently into several viral genomes at geographically distinct locations. This pattern seems to be more consistent with increased environmental pressure, e.g. from methylating pesticides, than with interaction with the PTGS system. CONCLUSIONS: The AlkB domain found in viral genomes is most likely a conventional DNA/RNA repair domain that protects the viral RNA genome against methylating compounds from the environment.",2005 Jan 3,"['Bratlie, Marit S', 'Drabløs, Finn']",BMC Genomics,,,False
823dc32e8b06f57fd36508ede418c620ae91562c,PMC,Bioinformatic mapping of AlkB homology domains in viruses,http://dx.doi.org/10.1186/1471-2164-6-1,PMC544882,15627404,CC BY,"BACKGROUND: AlkB-like proteins are members of the 2-oxoglutarate- and Fe(II)-dependent oxygenase superfamily. In Escherichia coli the protein protects RNA and DNA against damage from methylating agents. 1-methyladenine and 3-methylcytosine are repaired by oxidative demethylation and direct reversal of the methylated base back to its unmethylated form. Genes for AlkB homologues are widespread in nature, and Eukaryotes often have several genes coding for AlkB-like proteins. Similar domains have also been observed in certain plant viruses. The function of the viral domain is unknown, but it has been suggested that it may be involved in protecting the virus against the post-transcriptional gene silencing (PTGS) system found in plants. We wanted to do a phylogenomic mapping of viral AlkB-like domains as a basis for analysing functional aspects of these domains, because this could have some relevance for understanding possible alternative roles of AlkB homologues e.g. in Eukaryotes. RESULTS: Profile-based searches of protein sequence libraries showed that AlkB-like domains are found in at least 22 different single-stranded RNA positive-strand plant viruses, but mainly in a subgroup of the Flexiviridae family. Sequence analysis indicated that the AlkB domains probably are functionally conserved, and that they most likely have been integrated relatively recently into several viral genomes at geographically distinct locations. This pattern seems to be more consistent with increased environmental pressure, e.g. from methylating pesticides, than with interaction with the PTGS system. CONCLUSIONS: The AlkB domain found in viral genomes is most likely a conventional DNA/RNA repair domain that protects the viral RNA genome against methylating compounds from the environment.",2005 Jan 3,"['Bratlie, Marit S', 'Drabløs, Finn']",BMC Genomics,,,False
769398f7e7d03582fd05a4fbf322133e4509f5b7,PMC,Biosafety and Biosecurity in European Containment Level 3 Laboratories: Focus on French Recent Progress and Essential Requirements,http://dx.doi.org/10.3389/fpubh.2017.00121,PMC5449436,28620600,CC BY,"Even if European Union (EU) Member States are obliged to implement EU Directives 2000/54/EC on the protection of workers from risks related to exposure to biological agents at work, national biosafety regulations and practices varied from country to country. In fact, EU legislation on biological agents and genetically modified microorganisms is often not specific enough to ensure harmonization leading to difficulties in implementation for most laboratories. In the same way, biosecurity is a relatively new concept and a few EU Member States are known to have introduced national laboratory biosecurity legislation. In France, recent regulations have reinforced biosafety/biosecurity in containment level 3 (CL-3) laboratories but they concern a specific list of pathogens with no correlation in other European Members States. The objective of this review was to summarize European biosafety/biosecurity measures concerning CL-3 facilities focusing on French specificities. Essential requirements needed to preserve efficient biosafety measures when manipulating risk group 3 biological agents are highlighted. In addition, International, European and French standards related to containment laboratory planning, operation or biosafety equipment are described to clarify optimal biosafety and biosecurity requirements.",2017 May 31,"['Pastorino, Boris', 'de Lamballerie, Xavier', 'Charrel, Rémi']",Front Public Health,,,True
ace47aac143455a20fa2323df2cccbc6dc1b4166,PMC,Accurate characterization of the IFITM locus using MiSeq and PacBio sequencing shows genetic variation in Galliformes,http://dx.doi.org/10.1186/s12864-017-3801-8,PMC5450142,28558694,CC BY,"BACKGROUND: Interferon inducible transmembrane (IFITM) proteins are effectors of the immune system widely characterized for their role in restricting infection by diverse enveloped and non-enveloped viruses. The chicken IFITM (chIFITM) genes are clustered on chromosome 5 and to date four genes have been annotated, namely chIFITM1, chIFITM3, chIFITM5 and chIFITM10. However, due to poor assembly of this locus in the Gallus Gallus v4 genome, accurate characterization has so far proven problematic. Recently, a new chicken reference genome assembly Gallus Gallus v5 was generated using Sanger, 454, Illumina and PacBio sequencing technologies identifying considerable differences in the chIFITM locus over the previous genome releases. METHODS: We re-sequenced the locus using both Illumina MiSeq and PacBio RS II sequencing technologies and we mapped RNA-seq data from the European Nucleotide Archive (ENA) to this finalized chIFITM locus. Using SureSelect probes capture probes designed to the finalized chIFITM locus, we sequenced the locus of a different chicken breed, namely a White Leghorn, and a turkey. RESULTS: We confirmed the Gallus Gallus v5 consensus except for two insertions of 5 and 1 base pair within the chIFITM3 and B4GALNT4 genes, respectively, and a single base pair deletion within the B4GALNT4 gene. The pull down revealed a single amino acid substitution of A63V in the CIL domain of IFITM2 compared to Red Jungle fowl and 13, 13 and 11 differences between IFITM1, 2 and 3 of chickens and turkeys, respectively. RNA-seq shows chIFITM2 and chIFITM3 expression in numerous tissue types of different chicken breeds and avian cell lines, while the expression of the putative chIFITM1 is limited to the testis, caecum and ileum tissues. CONCLUSIONS: Locus resequencing using these capture probes and RNA-seq based expression analysis will allow the further characterization of genetic diversity within Galliformes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3801-8) contains supplementary material, which is available to authorized users.",2017 May 30,"['Bassano, Irene', 'Ong, Swee Hoe', 'Lawless, Nathan', 'Whitehead, Thomas', 'Fife, Mark', 'Kellam, Paul']",BMC Genomics,,,False
0629b1b64275da2120bfdb606bc8240d2a16ea5b,PMC,Accurate characterization of the IFITM locus using MiSeq and PacBio sequencing shows genetic variation in Galliformes,http://dx.doi.org/10.1186/s12864-017-3801-8,PMC5450142,28558694,CC BY,"BACKGROUND: Interferon inducible transmembrane (IFITM) proteins are effectors of the immune system widely characterized for their role in restricting infection by diverse enveloped and non-enveloped viruses. The chicken IFITM (chIFITM) genes are clustered on chromosome 5 and to date four genes have been annotated, namely chIFITM1, chIFITM3, chIFITM5 and chIFITM10. However, due to poor assembly of this locus in the Gallus Gallus v4 genome, accurate characterization has so far proven problematic. Recently, a new chicken reference genome assembly Gallus Gallus v5 was generated using Sanger, 454, Illumina and PacBio sequencing technologies identifying considerable differences in the chIFITM locus over the previous genome releases. METHODS: We re-sequenced the locus using both Illumina MiSeq and PacBio RS II sequencing technologies and we mapped RNA-seq data from the European Nucleotide Archive (ENA) to this finalized chIFITM locus. Using SureSelect probes capture probes designed to the finalized chIFITM locus, we sequenced the locus of a different chicken breed, namely a White Leghorn, and a turkey. RESULTS: We confirmed the Gallus Gallus v5 consensus except for two insertions of 5 and 1 base pair within the chIFITM3 and B4GALNT4 genes, respectively, and a single base pair deletion within the B4GALNT4 gene. The pull down revealed a single amino acid substitution of A63V in the CIL domain of IFITM2 compared to Red Jungle fowl and 13, 13 and 11 differences between IFITM1, 2 and 3 of chickens and turkeys, respectively. RNA-seq shows chIFITM2 and chIFITM3 expression in numerous tissue types of different chicken breeds and avian cell lines, while the expression of the putative chIFITM1 is limited to the testis, caecum and ileum tissues. CONCLUSIONS: Locus resequencing using these capture probes and RNA-seq based expression analysis will allow the further characterization of genetic diversity within Galliformes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3801-8) contains supplementary material, which is available to authorized users.",2017 May 30,"['Bassano, Irene', 'Ong, Swee Hoe', 'Lawless, Nathan', 'Whitehead, Thomas', 'Fife, Mark', 'Kellam, Paul']",BMC Genomics,,,False
bab4754e6414e57b1085e839c602053e49510939,PMC,Accurate characterization of the IFITM locus using MiSeq and PacBio sequencing shows genetic variation in Galliformes,http://dx.doi.org/10.1186/s12864-017-3801-8,PMC5450142,28558694,CC BY,"BACKGROUND: Interferon inducible transmembrane (IFITM) proteins are effectors of the immune system widely characterized for their role in restricting infection by diverse enveloped and non-enveloped viruses. The chicken IFITM (chIFITM) genes are clustered on chromosome 5 and to date four genes have been annotated, namely chIFITM1, chIFITM3, chIFITM5 and chIFITM10. However, due to poor assembly of this locus in the Gallus Gallus v4 genome, accurate characterization has so far proven problematic. Recently, a new chicken reference genome assembly Gallus Gallus v5 was generated using Sanger, 454, Illumina and PacBio sequencing technologies identifying considerable differences in the chIFITM locus over the previous genome releases. METHODS: We re-sequenced the locus using both Illumina MiSeq and PacBio RS II sequencing technologies and we mapped RNA-seq data from the European Nucleotide Archive (ENA) to this finalized chIFITM locus. Using SureSelect probes capture probes designed to the finalized chIFITM locus, we sequenced the locus of a different chicken breed, namely a White Leghorn, and a turkey. RESULTS: We confirmed the Gallus Gallus v5 consensus except for two insertions of 5 and 1 base pair within the chIFITM3 and B4GALNT4 genes, respectively, and a single base pair deletion within the B4GALNT4 gene. The pull down revealed a single amino acid substitution of A63V in the CIL domain of IFITM2 compared to Red Jungle fowl and 13, 13 and 11 differences between IFITM1, 2 and 3 of chickens and turkeys, respectively. RNA-seq shows chIFITM2 and chIFITM3 expression in numerous tissue types of different chicken breeds and avian cell lines, while the expression of the putative chIFITM1 is limited to the testis, caecum and ileum tissues. CONCLUSIONS: Locus resequencing using these capture probes and RNA-seq based expression analysis will allow the further characterization of genetic diversity within Galliformes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3801-8) contains supplementary material, which is available to authorized users.",2017 May 30,"['Bassano, Irene', 'Ong, Swee Hoe', 'Lawless, Nathan', 'Whitehead, Thomas', 'Fife, Mark', 'Kellam, Paul']",BMC Genomics,,,False
275c93ab31cb54dd94a1a2de585845829c98e3ae,PMC,Accurate characterization of the IFITM locus using MiSeq and PacBio sequencing shows genetic variation in Galliformes,http://dx.doi.org/10.1186/s12864-017-3801-8,PMC5450142,28558694,CC BY,"BACKGROUND: Interferon inducible transmembrane (IFITM) proteins are effectors of the immune system widely characterized for their role in restricting infection by diverse enveloped and non-enveloped viruses. The chicken IFITM (chIFITM) genes are clustered on chromosome 5 and to date four genes have been annotated, namely chIFITM1, chIFITM3, chIFITM5 and chIFITM10. However, due to poor assembly of this locus in the Gallus Gallus v4 genome, accurate characterization has so far proven problematic. Recently, a new chicken reference genome assembly Gallus Gallus v5 was generated using Sanger, 454, Illumina and PacBio sequencing technologies identifying considerable differences in the chIFITM locus over the previous genome releases. METHODS: We re-sequenced the locus using both Illumina MiSeq and PacBio RS II sequencing technologies and we mapped RNA-seq data from the European Nucleotide Archive (ENA) to this finalized chIFITM locus. Using SureSelect probes capture probes designed to the finalized chIFITM locus, we sequenced the locus of a different chicken breed, namely a White Leghorn, and a turkey. RESULTS: We confirmed the Gallus Gallus v5 consensus except for two insertions of 5 and 1 base pair within the chIFITM3 and B4GALNT4 genes, respectively, and a single base pair deletion within the B4GALNT4 gene. The pull down revealed a single amino acid substitution of A63V in the CIL domain of IFITM2 compared to Red Jungle fowl and 13, 13 and 11 differences between IFITM1, 2 and 3 of chickens and turkeys, respectively. RNA-seq shows chIFITM2 and chIFITM3 expression in numerous tissue types of different chicken breeds and avian cell lines, while the expression of the putative chIFITM1 is limited to the testis, caecum and ileum tissues. CONCLUSIONS: Locus resequencing using these capture probes and RNA-seq based expression analysis will allow the further characterization of genetic diversity within Galliformes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3801-8) contains supplementary material, which is available to authorized users.",2017 May 30,"['Bassano, Irene', 'Ong, Swee Hoe', 'Lawless, Nathan', 'Whitehead, Thomas', 'Fife, Mark', 'Kellam, Paul']",BMC Genomics,,,False
eddf8e52a9e165f59a4cb2ad0fbe4ea293aafd6b,PMC,Accurate characterization of the IFITM locus using MiSeq and PacBio sequencing shows genetic variation in Galliformes,http://dx.doi.org/10.1186/s12864-017-3801-8,PMC5450142,28558694,CC BY,"BACKGROUND: Interferon inducible transmembrane (IFITM) proteins are effectors of the immune system widely characterized for their role in restricting infection by diverse enveloped and non-enveloped viruses. The chicken IFITM (chIFITM) genes are clustered on chromosome 5 and to date four genes have been annotated, namely chIFITM1, chIFITM3, chIFITM5 and chIFITM10. However, due to poor assembly of this locus in the Gallus Gallus v4 genome, accurate characterization has so far proven problematic. Recently, a new chicken reference genome assembly Gallus Gallus v5 was generated using Sanger, 454, Illumina and PacBio sequencing technologies identifying considerable differences in the chIFITM locus over the previous genome releases. METHODS: We re-sequenced the locus using both Illumina MiSeq and PacBio RS II sequencing technologies and we mapped RNA-seq data from the European Nucleotide Archive (ENA) to this finalized chIFITM locus. Using SureSelect probes capture probes designed to the finalized chIFITM locus, we sequenced the locus of a different chicken breed, namely a White Leghorn, and a turkey. RESULTS: We confirmed the Gallus Gallus v5 consensus except for two insertions of 5 and 1 base pair within the chIFITM3 and B4GALNT4 genes, respectively, and a single base pair deletion within the B4GALNT4 gene. The pull down revealed a single amino acid substitution of A63V in the CIL domain of IFITM2 compared to Red Jungle fowl and 13, 13 and 11 differences between IFITM1, 2 and 3 of chickens and turkeys, respectively. RNA-seq shows chIFITM2 and chIFITM3 expression in numerous tissue types of different chicken breeds and avian cell lines, while the expression of the putative chIFITM1 is limited to the testis, caecum and ileum tissues. CONCLUSIONS: Locus resequencing using these capture probes and RNA-seq based expression analysis will allow the further characterization of genetic diversity within Galliformes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3801-8) contains supplementary material, which is available to authorized users.",2017 May 30,"['Bassano, Irene', 'Ong, Swee Hoe', 'Lawless, Nathan', 'Whitehead, Thomas', 'Fife, Mark', 'Kellam, Paul']",BMC Genomics,,,False
f8d76b64604150762d304fd8411541d9ec7b583c,PMC,Accurate characterization of the IFITM locus using MiSeq and PacBio sequencing shows genetic variation in Galliformes,http://dx.doi.org/10.1186/s12864-017-3801-8,PMC5450142,28558694,CC BY,"BACKGROUND: Interferon inducible transmembrane (IFITM) proteins are effectors of the immune system widely characterized for their role in restricting infection by diverse enveloped and non-enveloped viruses. The chicken IFITM (chIFITM) genes are clustered on chromosome 5 and to date four genes have been annotated, namely chIFITM1, chIFITM3, chIFITM5 and chIFITM10. However, due to poor assembly of this locus in the Gallus Gallus v4 genome, accurate characterization has so far proven problematic. Recently, a new chicken reference genome assembly Gallus Gallus v5 was generated using Sanger, 454, Illumina and PacBio sequencing technologies identifying considerable differences in the chIFITM locus over the previous genome releases. METHODS: We re-sequenced the locus using both Illumina MiSeq and PacBio RS II sequencing technologies and we mapped RNA-seq data from the European Nucleotide Archive (ENA) to this finalized chIFITM locus. Using SureSelect probes capture probes designed to the finalized chIFITM locus, we sequenced the locus of a different chicken breed, namely a White Leghorn, and a turkey. RESULTS: We confirmed the Gallus Gallus v5 consensus except for two insertions of 5 and 1 base pair within the chIFITM3 and B4GALNT4 genes, respectively, and a single base pair deletion within the B4GALNT4 gene. The pull down revealed a single amino acid substitution of A63V in the CIL domain of IFITM2 compared to Red Jungle fowl and 13, 13 and 11 differences between IFITM1, 2 and 3 of chickens and turkeys, respectively. RNA-seq shows chIFITM2 and chIFITM3 expression in numerous tissue types of different chicken breeds and avian cell lines, while the expression of the putative chIFITM1 is limited to the testis, caecum and ileum tissues. CONCLUSIONS: Locus resequencing using these capture probes and RNA-seq based expression analysis will allow the further characterization of genetic diversity within Galliformes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3801-8) contains supplementary material, which is available to authorized users.",2017 May 30,"['Bassano, Irene', 'Ong, Swee Hoe', 'Lawless, Nathan', 'Whitehead, Thomas', 'Fife, Mark', 'Kellam, Paul']",BMC Genomics,,,False
b5481d426a4547287ab83d451d7f7e2b3d1eace9,PMC,Accurate characterization of the IFITM locus using MiSeq and PacBio sequencing shows genetic variation in Galliformes,http://dx.doi.org/10.1186/s12864-017-3801-8,PMC5450142,28558694,CC BY,"BACKGROUND: Interferon inducible transmembrane (IFITM) proteins are effectors of the immune system widely characterized for their role in restricting infection by diverse enveloped and non-enveloped viruses. The chicken IFITM (chIFITM) genes are clustered on chromosome 5 and to date four genes have been annotated, namely chIFITM1, chIFITM3, chIFITM5 and chIFITM10. However, due to poor assembly of this locus in the Gallus Gallus v4 genome, accurate characterization has so far proven problematic. Recently, a new chicken reference genome assembly Gallus Gallus v5 was generated using Sanger, 454, Illumina and PacBio sequencing technologies identifying considerable differences in the chIFITM locus over the previous genome releases. METHODS: We re-sequenced the locus using both Illumina MiSeq and PacBio RS II sequencing technologies and we mapped RNA-seq data from the European Nucleotide Archive (ENA) to this finalized chIFITM locus. Using SureSelect probes capture probes designed to the finalized chIFITM locus, we sequenced the locus of a different chicken breed, namely a White Leghorn, and a turkey. RESULTS: We confirmed the Gallus Gallus v5 consensus except for two insertions of 5 and 1 base pair within the chIFITM3 and B4GALNT4 genes, respectively, and a single base pair deletion within the B4GALNT4 gene. The pull down revealed a single amino acid substitution of A63V in the CIL domain of IFITM2 compared to Red Jungle fowl and 13, 13 and 11 differences between IFITM1, 2 and 3 of chickens and turkeys, respectively. RNA-seq shows chIFITM2 and chIFITM3 expression in numerous tissue types of different chicken breeds and avian cell lines, while the expression of the putative chIFITM1 is limited to the testis, caecum and ileum tissues. CONCLUSIONS: Locus resequencing using these capture probes and RNA-seq based expression analysis will allow the further characterization of genetic diversity within Galliformes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3801-8) contains supplementary material, which is available to authorized users.",2017 May 30,"['Bassano, Irene', 'Ong, Swee Hoe', 'Lawless, Nathan', 'Whitehead, Thomas', 'Fife, Mark', 'Kellam, Paul']",BMC Genomics,,,False
3c51ef8a5ac17b4e6d461b5997f29a8324dd8a02,PMC,Accurate characterization of the IFITM locus using MiSeq and PacBio sequencing shows genetic variation in Galliformes,http://dx.doi.org/10.1186/s12864-017-3801-8,PMC5450142,28558694,CC BY,"BACKGROUND: Interferon inducible transmembrane (IFITM) proteins are effectors of the immune system widely characterized for their role in restricting infection by diverse enveloped and non-enveloped viruses. The chicken IFITM (chIFITM) genes are clustered on chromosome 5 and to date four genes have been annotated, namely chIFITM1, chIFITM3, chIFITM5 and chIFITM10. However, due to poor assembly of this locus in the Gallus Gallus v4 genome, accurate characterization has so far proven problematic. Recently, a new chicken reference genome assembly Gallus Gallus v5 was generated using Sanger, 454, Illumina and PacBio sequencing technologies identifying considerable differences in the chIFITM locus over the previous genome releases. METHODS: We re-sequenced the locus using both Illumina MiSeq and PacBio RS II sequencing technologies and we mapped RNA-seq data from the European Nucleotide Archive (ENA) to this finalized chIFITM locus. Using SureSelect probes capture probes designed to the finalized chIFITM locus, we sequenced the locus of a different chicken breed, namely a White Leghorn, and a turkey. RESULTS: We confirmed the Gallus Gallus v5 consensus except for two insertions of 5 and 1 base pair within the chIFITM3 and B4GALNT4 genes, respectively, and a single base pair deletion within the B4GALNT4 gene. The pull down revealed a single amino acid substitution of A63V in the CIL domain of IFITM2 compared to Red Jungle fowl and 13, 13 and 11 differences between IFITM1, 2 and 3 of chickens and turkeys, respectively. RNA-seq shows chIFITM2 and chIFITM3 expression in numerous tissue types of different chicken breeds and avian cell lines, while the expression of the putative chIFITM1 is limited to the testis, caecum and ileum tissues. CONCLUSIONS: Locus resequencing using these capture probes and RNA-seq based expression analysis will allow the further characterization of genetic diversity within Galliformes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3801-8) contains supplementary material, which is available to authorized users.",2017 May 30,"['Bassano, Irene', 'Ong, Swee Hoe', 'Lawless, Nathan', 'Whitehead, Thomas', 'Fife, Mark', 'Kellam, Paul']",BMC Genomics,,,True
18c21db94a22f1358057c6d797164ffe1585b395,PMC,"Dynamic changes of serum SARS-Coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge",http://dx.doi.org/10.1186/1465-9921-6-5,PMC545044,15638943,CC BY,"OBJECTIVE: The intent of this study was to examine the recovery of individuals who had been hospitalized for severe acute respiratory syndrome (SARS) in the year following their discharge from the hospital. Parameters studied included serum levels of SARS coronavirus (SARS-CoV) IgG antibody, tests of lung function, and imaging data to evaluate changes in lung fibrosis. In addition, we explored the incidence of femoral head necrosis in some of the individuals recovering from SARS. METHODS: The subjects of this study were 383 clinically diagnosed SARS patients in Beijing, China. They were tested regularly for serum levels of SARS-CoV IgG antibody and lung function and were given chest X-rays and/or high resolution computerized tomography (HRCT) examinations at the Chinese PLA General Hospital during the 12 months that followed their release from the hospital. Those individuals who were found to have lung diffusion abnormities (transfer coefficient for carbon monoxide [D(L)CO] < 80% of predicted value [pred]) received regular lung function tests and HRCT examinations in the follow-up phase in order to document the changes in their lung condition. Some patients who complained of joint pain were given magnetic resonance imaging (MRI) examinations of their femoral heads. FINDINGS: Of all the subjects, 81.2% (311 of 383 patients) tested positive for serum SARS-CoV IgG. Of those testing positive, 27.3% (85 of 311 patients) were suffering from lung diffusion abnormities (D(L)CO < 80% pred) and 21.5% (67 of 311 patients) exhibited lung fibrotic changes. In the 12 month duration of this study, all of the 40 patients with lung diffusion abnormities who were examined exhibited some improvement of lung function and fibrosis detected by radiography. Of the individuals receiving MRI examinations, 23.1% (18 of 78 patients) showed signs of femoral head necrosis. INTERPRETATION: The lack of sero-positive SARS-CoV in some individuals suggests that there may have been some misdiagnosed cases among the subjects included in this study. Of those testing positive, the serum levels of SARS-CoV IgG antibody decreased significantly during the 12 months after hospital discharge. Additionally, we found that the individuals who had lung fibrosis showed some spontaneous recovery. Finally, some of the subjects developed femoral head necrosis.",2005 Jan 8,"['Xie, Lixin', 'Liu, Youning', 'Fan, Baoxing', 'Xiao, Yueyong', 'Tian, Qing', 'Chen, Liangan', 'Zhao, Hong', 'Chen, Weijun']",Respir Res,,,True
8d7400a2b387820cd391d7df8194642e50402a0c,PMC,Protein secretion in Lactococcus lactis : an efficient way to increase the overall heterologous protein production,http://dx.doi.org/10.1186/1475-2859-4-2,PMC545053,15631634,CC BY,"Lactococcus lactis, the model lactic acid bacterium (LAB), is a food grade and well-characterized Gram positive bacterium. It is a good candidate for heterologous protein delivery in foodstuff or in the digestive tract. L. lactis can also be used as a protein producer in fermentor. Many heterologous proteins have already been produced in L. lactis but only few reports allow comparing production yields for a given protein either produced intracellularly or secreted in the medium. Here, we review several works evaluating the influence of the localization on the production yields of several heterologous proteins produced in L. lactis. The questions of size limits, conformation, and proteolysis are addressed and discussed with regard to protein yields. These data show that i) secretion is preferable to cytoplasmic production; ii) secretion enhancement (by signal peptide and propeptide optimization) results in increased production yield; iii) protein conformation rather than protein size can impair secretion and thus alter production yields; and iv) fusion of a stable protein can stabilize labile proteins. The role of intracellular proteolysis on heterologous cytoplasmic proteins and precursors is discussed. The new challenges now are the development of food grade systems and the identification and optimization of host factors affecting heterologous protein production not only in L. lactis, but also in other LAB species.",2005 Jan 4,"['Le Loir, Yves', 'Azevedo, Vasco', 'Oliveira, Sergio C', 'Freitas, Daniela A', 'Miyoshi, Anderson', 'Bermúdez-Humarán, Luis G', 'Nouaille, Sébastien', 'Ribeiro, Luciana A', 'Leclercq, Sophie', 'Gabriel, Jane E', 'Guimaraes, Valeria D', 'Oliveira, Maricê N', 'Charlier, Cathy', 'Gautier, Michel', 'Langella, Philippe']",Microb Cell Fact,,,True
90c1ab8b02263998f809915b0629da5aa1cbc47a,PMC,Accuracy of parents in measuring body temperature with a tympanic thermometer,http://dx.doi.org/10.1186/1471-2296-6-3,PMC545063,15644134,CC BY,"BACKGROUND: It is now common for parents to measure tympanic temperatures in children. The objective of this study was to assess the diagnostic accuracy of these measurements. METHODS: Parents and then nurses measured the temperature of 60 children with a tympanic thermometer designed for home use (home thermometer). The reference standard was a temperature measured by a nurse with a model of tympanic thermometer commonly used in hospitals (hospital thermometer). A difference of ≥ 0.5 °C was considered clinically significant. A fever was defined as a temperature ≥ 38.5 °C. RESULTS: The mean absolute difference between the readings done by the parent and the nurse with the home thermometer was 0.44 ± 0.61 °C, and 33% of the readings differed by ≥ 0.5 °C. The mean absolute difference between the readings done by the parent with the home thermometer and the nurse with the hospital thermometer was 0.51 ± 0.63 °C, and 72 % of the readings differed by ≥ 0.5 °C. Using the home thermometer, parents detected fever with a sensitivity of 76% (95% CI 50–93%), a specificity of 95% (95% CI 84–99%), a positive predictive value of 87% (95% CI 60–98%), and a negative predictive value of 91% (95% CI 79–98 %). In comparing the readings the nurse obtained from the two different tympanic thermometers, the mean absolute difference was 0.24 ± 0.22 °C. Nurses detected fever with a sensitivity of 94% (95 % CI 71–100 %), a specificity of 88% (95% CI 75–96 %), a positive predictive value of 76% (95% CI 53–92%), and a negative predictive value of 97% (95%CI 87–100 %) using the home thermometer. The intraclass correlation coefficient for the three sets of readings was 0.80, and the consistency of readings was not affected by the body temperature. CONCLUSIONS: The readings done by parents with a tympanic thermometer designed for home use differed a clinically significant amount from the reference standard (readings done by nurses with a model of tympanic thermometer commonly used in hospitals) the majority of the time, and parents failed to detect fever about one-quarter of the time. Tympanic readings reported by parents should be interpreted with great caution.",2005 Jan 11,"['Robinson, Joan L', 'Jou, Hsing', 'Spady, Donald W']",BMC Fam Pract,,,True
3838015252b0ac31630c87d5cb719869e1569aa3,PMC,Bocavirus Viremia and Hepatitis in an Immunocompetent Child,http://dx.doi.org/10.4274/balkanmedj.2015.1492,PMC5450871,28443581,CC BY,"BACKGROUND: So far, many studies have shown that Human Bocavirus ( HBoV) is the main pathogen of the respiratory tract. Until now, there is no study that proves the association between HBoV and hepatitis. HBoV viremia/DNAemia has been associated closely with acute primary infection and moderate-to-severe illness but, more detailed clinical data about HBoV dissemination are still unavailable. CASE REPORT: Here we report a 2-years-5-months-old girl suffering from respiratory distress and heptitis followed in our intensive care unit. HBoV was detected in our patients nose and throat swabs concurrent with whole blood sample by positive polymerase chain reactions. After a through investigation no causative agent other than HBoV viremia was found. CONCLUSION: Human Bocavirus viremia with high viral loads may be associated with hepatitis.",2017 May 15,"['Haytoğlu, Zeliha', 'Canan, Oğuz']",Balkan Med J,,,True
12bc05b6a9ae2d8823f67b0a8200fb7f72c45f9b,PMC,Febrile Rhinovirus Illness During Pregnancy Is Associated With Low Birth Weight in Nepal,http://dx.doi.org/10.1093/ofid/ofx073,PMC5450902,28584855,CC BY,"BACKGROUND: Adverse birth outcomes, including low birth weight (LBW), defined as <2500 grams, small-for-gestational-age (SGA), and prematurity, contribute to 60%–80% of infant mortality worldwide and may be related to infections during pregnancy. The aim of this study was to assess whether febrile human rhinovirus (HRV) illness is associated with adverse birth outcomes. METHODS: Active household-based weekly surveillance was performed for respiratory illness episodes in pregnant women as part of a community-based, prospective, randomized trial of maternal influenza immunization in rural Nepal. Rhinovirus (HRV) febrile illness episodes were defined as fever plus cough, sore throat, runny nose, and/or myalgia with HRV detected on mid-nasal swab. Multivariate regression analysis evaluated the association between febrile HRV respiratory illness and adverse birth outcomes. RESULTS: Overall, 96 (3%) of 3693 pregnant women had HRV-positive febrile respiratory illnesses. Infants born to pregnant women with HRV febrile illness had a 1.6-fold increased risk of being LBW compared with those with non-HRV febrile illness (28 of 96 [38%] vs 109 of 458 [24%]; relative risk [RR], 1.6; 95% confidence interval [CI], 1.1–2.3). No difference in risk of LBW was observed between infants born to mothers with non-HRV febrile respiratory illness and those without respiratory illness during pregnancy (109 of 458 [24%] vs 552 of 2220 [25%], respectively; RR, 1.0; 95% CI, 0.8–1.2). CONCLUSIONS: Febrile illness due to rhinovirus during pregnancy was associated with increased risk of LBW in a rural South Asian population. Interventions to reduce the burden of febrile respiratory illness due to rhinovirus during pregnancy may have a significant impact on LBW and subsequent infant mortality.",2017 Apr 6,"['Philpott, Erin K', 'Englund, Janet A', 'Katz, Joanne', 'Tielsch, James', 'Khatry, Subarna', 'LeClerq, Stephen C', 'Shrestha, Laxman', 'Kuypers, Jane', 'Magaret, Amalia S', 'Steinhoff, Mark C', 'Chu, Helen Y']",Open Forum Infect Dis,,,True
eb4451db661165d4d518ea8b812b9d0963e84736,PMC,Potent and selective inhibition of pathogenic viruses by engineered ubiquitin variants,http://dx.doi.org/10.1371/journal.ppat.1006372,PMC5451084,28542609,CC BY,"The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses. A variety of viral DUBs (vDUBs), including the MERS-CoV papain-like protease, are responsible for cleaving the viral replicase polyproteins during replication, and are thereby critical components of the viral replication cycle. Together, this makes vDUBs highly attractive antiviral drug targets. However, structural similarity between the catalytic cores of vDUBs and human DUBs complicates the development of selective small molecule vDUB inhibitors. We have thus developed an alternative strategy to target the vDUB activity through a rational protein design approach. Here, we report the use of phage-displayed ubiquitin variant (UbV) libraries to rapidly identify potent and highly selective protein-based inhibitors targeting the DUB domains of MERS-CoV and CCHFV. UbVs bound the vDUBs with high affinity and specificity to inhibit deubiquitination, deISGylation and in the case of MERS-CoV also viral replicative polyprotein processing. Co-crystallization studies further revealed critical molecular interactions between UbVs and MERS-CoV or CCHFV vDUBs, accounting for the observed binding specificity and high affinity. Finally, expression of UbVs during MERS-CoV infection reduced infectious progeny titers by more than four orders of magnitude, demonstrating the remarkable potency of UbVs as antiviral agents. Our results thereby establish a strategy to produce protein-based inhibitors that could protect against a diverse range of viruses by providing UbVs via mRNA or protein delivery technologies or through transgenic techniques.",2017 May 18,"['Zhang, Wei', 'Bailey-Elkin, Ben A.', 'Knaap, Robert C. M.', 'Khare, Baldeep', 'Dalebout, Tim J.', 'Johnson, Garrett G.', 'van Kasteren, Puck B.', 'McLeish, Nigel J.', 'Gu, Jun', 'He, Wenguang', 'Kikkert, Marjolein', 'Mark, Brian L.', 'Sidhu, Sachdev S.']",PLoS Pathog,,,True
3fb6568d231cdc067a749d9e71a92a8722a0e0f3,PMC,Potent and selective inhibition of pathogenic viruses by engineered ubiquitin variants,http://dx.doi.org/10.1371/journal.ppat.1006372,PMC5451084,28542609,CC BY,"The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses. A variety of viral DUBs (vDUBs), including the MERS-CoV papain-like protease, are responsible for cleaving the viral replicase polyproteins during replication, and are thereby critical components of the viral replication cycle. Together, this makes vDUBs highly attractive antiviral drug targets. However, structural similarity between the catalytic cores of vDUBs and human DUBs complicates the development of selective small molecule vDUB inhibitors. We have thus developed an alternative strategy to target the vDUB activity through a rational protein design approach. Here, we report the use of phage-displayed ubiquitin variant (UbV) libraries to rapidly identify potent and highly selective protein-based inhibitors targeting the DUB domains of MERS-CoV and CCHFV. UbVs bound the vDUBs with high affinity and specificity to inhibit deubiquitination, deISGylation and in the case of MERS-CoV also viral replicative polyprotein processing. Co-crystallization studies further revealed critical molecular interactions between UbVs and MERS-CoV or CCHFV vDUBs, accounting for the observed binding specificity and high affinity. Finally, expression of UbVs during MERS-CoV infection reduced infectious progeny titers by more than four orders of magnitude, demonstrating the remarkable potency of UbVs as antiviral agents. Our results thereby establish a strategy to produce protein-based inhibitors that could protect against a diverse range of viruses by providing UbVs via mRNA or protein delivery technologies or through transgenic techniques.",2017 May 18,"['Zhang, Wei', 'Bailey-Elkin, Ben A.', 'Knaap, Robert C. M.', 'Khare, Baldeep', 'Dalebout, Tim J.', 'Johnson, Garrett G.', 'van Kasteren, Puck B.', 'McLeish, Nigel J.', 'Gu, Jun', 'He, Wenguang', 'Kikkert, Marjolein', 'Mark, Brian L.', 'Sidhu, Sachdev S.']",PLoS Pathog,,,False
3a24f9357129bacec26d7f82f319431003d29f96,PMC,Potent and selective inhibition of pathogenic viruses by engineered ubiquitin variants,http://dx.doi.org/10.1371/journal.ppat.1006372,PMC5451084,28542609,CC BY,"The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses. A variety of viral DUBs (vDUBs), including the MERS-CoV papain-like protease, are responsible for cleaving the viral replicase polyproteins during replication, and are thereby critical components of the viral replication cycle. Together, this makes vDUBs highly attractive antiviral drug targets. However, structural similarity between the catalytic cores of vDUBs and human DUBs complicates the development of selective small molecule vDUB inhibitors. We have thus developed an alternative strategy to target the vDUB activity through a rational protein design approach. Here, we report the use of phage-displayed ubiquitin variant (UbV) libraries to rapidly identify potent and highly selective protein-based inhibitors targeting the DUB domains of MERS-CoV and CCHFV. UbVs bound the vDUBs with high affinity and specificity to inhibit deubiquitination, deISGylation and in the case of MERS-CoV also viral replicative polyprotein processing. Co-crystallization studies further revealed critical molecular interactions between UbVs and MERS-CoV or CCHFV vDUBs, accounting for the observed binding specificity and high affinity. Finally, expression of UbVs during MERS-CoV infection reduced infectious progeny titers by more than four orders of magnitude, demonstrating the remarkable potency of UbVs as antiviral agents. Our results thereby establish a strategy to produce protein-based inhibitors that could protect against a diverse range of viruses by providing UbVs via mRNA or protein delivery technologies or through transgenic techniques.",2017 May 18,"['Zhang, Wei', 'Bailey-Elkin, Ben A.', 'Knaap, Robert C. M.', 'Khare, Baldeep', 'Dalebout, Tim J.', 'Johnson, Garrett G.', 'van Kasteren, Puck B.', 'McLeish, Nigel J.', 'Gu, Jun', 'He, Wenguang', 'Kikkert, Marjolein', 'Mark, Brian L.', 'Sidhu, Sachdev S.']",PLoS Pathog,,,False
d63201b4350a82c89280d64cf8a0fcbdffaaf40c,PMC,PTH[1-34] improves the effects of core decompression in early-stage steroid-associated osteonecrosis model by enhancing bone repair and revascularization,http://dx.doi.org/10.1371/journal.pone.0178781,PMC5451136,28562696,CC BY,"Steroid-associated osteonecrosis (SAON) might induce bone collapse and subsequently lead to joint arthroplasty. Core decompression (CD) is regarded as an effective therapy for early-stage SAON, but the prognosis is unsatisfactory due to incomplete bone repair. Parathyroid hormone[1–34] (PTH[1–34]) has demonstrated positive efficacy in promoting bone formation. We therefore evaluated the effects of PTH on improving the effects of CD in Early-Stage SAON. Distal femoral CD was performed two weeks after osteonecrosis induction or vehicle injection, with ten of the ON-induced rabbits being subjected to six-week PTH[1–34] treatment and the others, including ON-induced and non-induced rabbits, being treated with vehicle. MRI confirmed that intermittent PTH administration improved SAON after CD therapy. Micro-CT showed increased bone formation within the tunnel. Bone repair was enhanced with decreased empty osteocyte lacunae and necrosis foci area, resulting in enhanced peak load and stiffness of the tunnel. Additionally, PTH enlarged the mean diameter of vessels in the marrow and increased the number of vessels within the tunnels, as well as elevated the expression of BMP-2, RUNX2, IGF-1, bFGF and VEGF, together with serum OCN and VEGF levels. Therefore, PTH[1–34] enhances the efficacy of CD on osteogenesis and neovascularization, thus promoting bone and blood vessels repair in the SAON model.",2017 May 31,"['Zhou, Chen-he', 'Meng, Jia-hong', 'Zhao, Chen-chen', 'Ye, Chen-yi', 'Zhu, Han-xiao', 'Hu, Bin', 'Heng, Boon Chin', 'Shen, Yue', 'Lin, Tiao', 'Yang, Xiao-bo', 'Shi, Zhong-li', 'Shen, Wei-liang', 'Yan, Shi-gui']",PLoS One,,,True
39e066c95d89964b9cd608c14fc5e2077706e72e,PMC,Deep Sequencing in Infectious Diseases: Immune and Pathogen Repertoires for the Improvement of Patient Outcomes,http://dx.doi.org/10.3389/fimmu.2017.00593,PMC5451494,28620372,CC BY,"The inaugural workshop “Deep Sequencing in Infectious Diseases: Immune and Pathogen Repertoires for the Improvement of Patient Outcomes” was held in Singapore on 13–14 October 2016. The aim of the workshop was to discuss the latest trends in using high-throughput sequencing, bioinformatics, and allied technologies to analyze immune and pathogen repertoires and their interplay within the host, bringing together key international players in the field and Singapore-based researchers and clinician-scientists. The focus was in particular on the application of these technologies for the improvement of patient diagnosis, prognosis and treatment, and for other broad public health outcomes. The presentations by scientists and clinicians showed the potential of deep sequencing technology to capture the coevolution of adaptive immunity and pathogens. For clinical applications, some key challenges remain, such as the long turnaround time and relatively high cost of deep sequencing for pathogen identification and characterization and the lack of international standardization in immune repertoire analysis.",2017 Jun 1,"['Burkholder, William F.', 'Newell, Evan W.', 'Poidinger, Michael', 'Chen, Swaine', 'Fink, Katja']",Front Immunol,,,True
28deef160eb2e879ffa3a4f025898a9690be0e7e,PMC,"Golgi anti-apoptotic protein: a tale of camels, calcium, channels and cancer",http://dx.doi.org/10.1098/rsob.170045,PMC5451544,28469007,CC BY,"Golgi anti-apoptotic protein (GAAP), also known as transmembrane Bax inhibitor-1 motif-containing 4 (TMBIM4) or Lifeguard 4 (Lfg4), shares remarkable amino acid conservation with orthologues throughout eukaryotes, prokaryotes and some orthopoxviruses, suggesting a highly conserved function. GAAPs regulate Ca(2+) levels and fluxes from the Golgi and endoplasmic reticulum, confer resistance to a broad range of apoptotic stimuli, promote cell adhesion and migration via the activation of store-operated Ca(2+) entry, are essential for the viability of human cells, and affect orthopoxvirus virulence. GAAPs are oligomeric, multi-transmembrane proteins that are resident in Golgi membranes and form cation-selective ion channels that may explain the multiple functions of these proteins. Residues contributing to the ion-conducting pore have been defined and provide the first clues about the mechanistic link between these very different functions of GAAP. Although GAAPs are naturally oligomeric, they can also function as monomers, a feature that distinguishes them from other virus-encoded ion channels that must oligomerize for function. This review summarizes the known functions of GAAPs and discusses their potential importance in disease.",2017 May 3,"['Carrara, Guia', 'Parsons, Maddy', 'Saraiva, Nuno', 'Smith, Geoffrey L.']",Open Biol,,,True
e398a3cd7f7d75bc06f0f15103309511299bb653,PMC,Assessing the use of mobile phone data to describe recurrent mobility patterns in spatial epidemic models,http://dx.doi.org/10.1098/rsos.160950,PMC5451791,28572990,CC BY,"The recent availability of large-scale call detail record data has substantially improved our ability of quantifying human travel patterns with broad applications in epidemiology. Notwithstanding a number of successful case studies, previous works have shown that using different mobility data sources, such as mobile phone data or census surveys, to parametrize infectious disease models can generate divergent outcomes. Thus, it remains unclear to what extent epidemic modelling results may vary when using different proxies for human movements. Here, we systematically compare 658 000 simulated outbreaks generated with a spatially structured epidemic model based on two different human mobility networks: a commuting network of France extracted from mobile phone data and another extracted from a census survey. We compare epidemic patterns originating from all the 329 possible outbreak seed locations and identify the structural network properties of the seeding nodes that best predict spatial and temporal epidemic patterns to be alike. We find that similarity of simulated epidemics is significantly correlated to connectivity, traffic and population size of the seeding nodes, suggesting that the adequacy of mobile phone data for infectious disease models becomes higher when epidemics spread between highly connected and heavily populated locations, such as large urban areas.",2017 May 17,"['Panigutti, Cecilia', 'Tizzoni, Michele', 'Bajardi, Paolo', 'Smoreda, Zbigniew', 'Colizza, Vittoria']",R Soc Open Sci,,,True
865f101ce80657e1347a4a35dabfa911a3072429,PMC,Trade and Health: Is the Health Community Ready for Action?,http://dx.doi.org/10.1371/journal.pmed.0020008,PMC545201,15696218,CC BY,There are greater tensions than ever before between promoting trade and protecting health. Human health could lose out to trade liberalization unless the health community fights its case,2005 Jan 25,"['Lee, Kelley', 'Koivusalo, Meri']",PLoS Med,,,True
fcb1ba715b2516823fee057cbb0f8276c76d19d7,PMC,Characterisation of the canine faecal virome in healthy dogs and dogs with acute diarrhoea using shotgun metagenomics,http://dx.doi.org/10.1371/journal.pone.0178433,PMC5453527,28570584,CC BY,"The virome has been increasingly investigated in numerous animal species and in different sites of the body, facilitating the identification and discovery of a variety of viruses. In spite of this, the faecal virome of healthy dogs has not been investigated. In this study we describe the faecal virome of healthy dogs and dogs with acute diarrhoea in Australia, using a shotgun metagenomic approach. Viral sequences from a range of different virus families, including both RNA and DNA families, and known pathogens implicated in enteric disease were documented. Twelve viral families were identified, of which four were bacteriophages. Eight eukaryotic viral families were detected: Astroviridae, Coronaviridae, Reoviridae, Picornaviridae, Caliciviridae, Parvoviridae, Adenoviridae and Papillomaviridae. Families Astroviridae, Picornaviridae and Caliciviridae were found only in dogs with acute diarrhoea, with Astroviridae being the most common family identified in this group. Due to its prevalence, characterisation the complete genome of a canine astrovirus was performed. These studies indicate that metagenomic analyses are useful for the investigation of viral populations in the faeces of dogs. Further studies to elucidate the epidemiological and biological relevance of these findings are warranted.",2017 Jun 1,"['Moreno, Paloma S.', 'Wagner, Josef', 'Mansfield, Caroline S.', 'Stevens, Matthew', 'Gilkerson, James R.', 'Kirkwood, Carl D.']",PLoS One,,,True
37f4296e5715d50d423e79b939b51bb9c2b98590,PMC,Characterisation of the canine faecal virome in healthy dogs and dogs with acute diarrhoea using shotgun metagenomics,http://dx.doi.org/10.1371/journal.pone.0178433,PMC5453527,28570584,CC BY,"The virome has been increasingly investigated in numerous animal species and in different sites of the body, facilitating the identification and discovery of a variety of viruses. In spite of this, the faecal virome of healthy dogs has not been investigated. In this study we describe the faecal virome of healthy dogs and dogs with acute diarrhoea in Australia, using a shotgun metagenomic approach. Viral sequences from a range of different virus families, including both RNA and DNA families, and known pathogens implicated in enteric disease were documented. Twelve viral families were identified, of which four were bacteriophages. Eight eukaryotic viral families were detected: Astroviridae, Coronaviridae, Reoviridae, Picornaviridae, Caliciviridae, Parvoviridae, Adenoviridae and Papillomaviridae. Families Astroviridae, Picornaviridae and Caliciviridae were found only in dogs with acute diarrhoea, with Astroviridae being the most common family identified in this group. Due to its prevalence, characterisation the complete genome of a canine astrovirus was performed. These studies indicate that metagenomic analyses are useful for the investigation of viral populations in the faeces of dogs. Further studies to elucidate the epidemiological and biological relevance of these findings are warranted.",2017 Jun 1,"['Moreno, Paloma S.', 'Wagner, Josef', 'Mansfield, Caroline S.', 'Stevens, Matthew', 'Gilkerson, James R.', 'Kirkwood, Carl D.']",PLoS One,,,False
ebf93f3417e20a020b4e3d3d088e17f07f829941,PMC,Characterisation of the canine faecal virome in healthy dogs and dogs with acute diarrhoea using shotgun metagenomics,http://dx.doi.org/10.1371/journal.pone.0178433,PMC5453527,28570584,CC BY,"The virome has been increasingly investigated in numerous animal species and in different sites of the body, facilitating the identification and discovery of a variety of viruses. In spite of this, the faecal virome of healthy dogs has not been investigated. In this study we describe the faecal virome of healthy dogs and dogs with acute diarrhoea in Australia, using a shotgun metagenomic approach. Viral sequences from a range of different virus families, including both RNA and DNA families, and known pathogens implicated in enteric disease were documented. Twelve viral families were identified, of which four were bacteriophages. Eight eukaryotic viral families were detected: Astroviridae, Coronaviridae, Reoviridae, Picornaviridae, Caliciviridae, Parvoviridae, Adenoviridae and Papillomaviridae. Families Astroviridae, Picornaviridae and Caliciviridae were found only in dogs with acute diarrhoea, with Astroviridae being the most common family identified in this group. Due to its prevalence, characterisation the complete genome of a canine astrovirus was performed. These studies indicate that metagenomic analyses are useful for the investigation of viral populations in the faeces of dogs. Further studies to elucidate the epidemiological and biological relevance of these findings are warranted.",2017 Jun 1,"['Moreno, Paloma S.', 'Wagner, Josef', 'Mansfield, Caroline S.', 'Stevens, Matthew', 'Gilkerson, James R.', 'Kirkwood, Carl D.']",PLoS One,,,False
5e4e1fabdad0bef4c21d9b1cead61958e13d0fb5,PMC,Characterisation of the canine faecal virome in healthy dogs and dogs with acute diarrhoea using shotgun metagenomics,http://dx.doi.org/10.1371/journal.pone.0178433,PMC5453527,28570584,CC BY,"The virome has been increasingly investigated in numerous animal species and in different sites of the body, facilitating the identification and discovery of a variety of viruses. In spite of this, the faecal virome of healthy dogs has not been investigated. In this study we describe the faecal virome of healthy dogs and dogs with acute diarrhoea in Australia, using a shotgun metagenomic approach. Viral sequences from a range of different virus families, including both RNA and DNA families, and known pathogens implicated in enteric disease were documented. Twelve viral families were identified, of which four were bacteriophages. Eight eukaryotic viral families were detected: Astroviridae, Coronaviridae, Reoviridae, Picornaviridae, Caliciviridae, Parvoviridae, Adenoviridae and Papillomaviridae. Families Astroviridae, Picornaviridae and Caliciviridae were found only in dogs with acute diarrhoea, with Astroviridae being the most common family identified in this group. Due to its prevalence, characterisation the complete genome of a canine astrovirus was performed. These studies indicate that metagenomic analyses are useful for the investigation of viral populations in the faeces of dogs. Further studies to elucidate the epidemiological and biological relevance of these findings are warranted.",2017 Jun 1,"['Moreno, Paloma S.', 'Wagner, Josef', 'Mansfield, Caroline S.', 'Stevens, Matthew', 'Gilkerson, James R.', 'Kirkwood, Carl D.']",PLoS One,,,False
12e04f9e960b0fe9e5d0815482100920c29ca7f1,PMC,Characterisation of the canine faecal virome in healthy dogs and dogs with acute diarrhoea using shotgun metagenomics,http://dx.doi.org/10.1371/journal.pone.0178433,PMC5453527,28570584,CC BY,"The virome has been increasingly investigated in numerous animal species and in different sites of the body, facilitating the identification and discovery of a variety of viruses. In spite of this, the faecal virome of healthy dogs has not been investigated. In this study we describe the faecal virome of healthy dogs and dogs with acute diarrhoea in Australia, using a shotgun metagenomic approach. Viral sequences from a range of different virus families, including both RNA and DNA families, and known pathogens implicated in enteric disease were documented. Twelve viral families were identified, of which four were bacteriophages. Eight eukaryotic viral families were detected: Astroviridae, Coronaviridae, Reoviridae, Picornaviridae, Caliciviridae, Parvoviridae, Adenoviridae and Papillomaviridae. Families Astroviridae, Picornaviridae and Caliciviridae were found only in dogs with acute diarrhoea, with Astroviridae being the most common family identified in this group. Due to its prevalence, characterisation the complete genome of a canine astrovirus was performed. These studies indicate that metagenomic analyses are useful for the investigation of viral populations in the faeces of dogs. Further studies to elucidate the epidemiological and biological relevance of these findings are warranted.",2017 Jun 1,"['Moreno, Paloma S.', 'Wagner, Josef', 'Mansfield, Caroline S.', 'Stevens, Matthew', 'Gilkerson, James R.', 'Kirkwood, Carl D.']",PLoS One,,,False
81e91321cec539baf72d8e1e87b0a6a384c6d9cf,PMC,Characterisation of the canine faecal virome in healthy dogs and dogs with acute diarrhoea using shotgun metagenomics,http://dx.doi.org/10.1371/journal.pone.0178433,PMC5453527,28570584,CC BY,"The virome has been increasingly investigated in numerous animal species and in different sites of the body, facilitating the identification and discovery of a variety of viruses. In spite of this, the faecal virome of healthy dogs has not been investigated. In this study we describe the faecal virome of healthy dogs and dogs with acute diarrhoea in Australia, using a shotgun metagenomic approach. Viral sequences from a range of different virus families, including both RNA and DNA families, and known pathogens implicated in enteric disease were documented. Twelve viral families were identified, of which four were bacteriophages. Eight eukaryotic viral families were detected: Astroviridae, Coronaviridae, Reoviridae, Picornaviridae, Caliciviridae, Parvoviridae, Adenoviridae and Papillomaviridae. Families Astroviridae, Picornaviridae and Caliciviridae were found only in dogs with acute diarrhoea, with Astroviridae being the most common family identified in this group. Due to its prevalence, characterisation the complete genome of a canine astrovirus was performed. These studies indicate that metagenomic analyses are useful for the investigation of viral populations in the faeces of dogs. Further studies to elucidate the epidemiological and biological relevance of these findings are warranted.",2017 Jun 1,"['Moreno, Paloma S.', 'Wagner, Josef', 'Mansfield, Caroline S.', 'Stevens, Matthew', 'Gilkerson, James R.', 'Kirkwood, Carl D.']",PLoS One,,,False
09525027db30dc3a6945da255f80b2099e239c48,PMC,Structural basis of nectin-1 recognition by pseudorabies virus glycoprotein D,http://dx.doi.org/10.1371/journal.ppat.1006314,PMC5453625,28542478,CC BY,"An early and yet indispensable step in the alphaherpesvirus infection is the engagement of host receptors by the viral envelope glycoprotein D (gD). Of the thus-far identified gD receptors, nectin-1 is likely the most effective in terms of its wide usage by multiple alphaherpesviruses for cell entry. The molecular basis of nectin-1 recognition by the gD protein is therefore an interesting scientific question in the alphaherpesvirus field. Previous studies focused on the herpes simplex virus (HSV) of the Simplexvirus genus, for which both the free gD structure and the gD/nectin-1 complex structure were reported at high resolutions. The structural and functional features of other alphaherpesviral gDs, however, remain poorly characterized. In the current study, we systematically studied the characteristics of nectin-1 binding by the gD of a Varicellovirus genus member, the pseudorabies virus (PRV). We first showed that PRV infects host cells via both human and swine nectin-1, and that its gD exhibits similar binding affinities for nectin-1 of the two species. Furthermore, we demonstrated that removal of the PRV gD membrane-proximal residues could significantly increase its affinity for the receptor binding. The structures of PRV gD in the free and the nectin-1-bound states were then solved, revealing a similar overall 3D fold as well as a homologous nectin-1 binding mode to its HSV counterpart. However, several unique features were observed at the binding interface of PRV gD, enabling the viral ligand to utilize different gD residues (from those of HSV) for nectin-1 engagement. These observed binding characteristics were further verified by the mutagenesis study using the key-residue mutants of nectin-1. The structural and functional data obtained in this study, therefore, provide the basis of receptor recognition by PRV gD.",2017 May 19,"['Li, An', 'Lu, Guangwen', 'Qi, Jianxun', 'Wu, Lili', 'Tian, Kegong', 'Luo, Tingrong', 'Shi, Yi', 'Yan, Jinghua', 'Gao, George F.']",PLoS Pathog,,,True
c8d7f93deaccea9d11f6713cc20368d236fc3d82,PMC,The Broad Host Range and Genetic Diversity of Mammalian and Avian Astroviruses,http://dx.doi.org/10.3390/v9050102,PMC5454415,28489047,CC BY,"Astroviruses are a diverse family of viruses that infect a wide range of mammalian and avian hosts. Here we describe the phylogenetic diversity and current classification methodology of astroviruses based on the ORF1b and ORF2 genes, highlighting the propensity of astroviruses to undergo interspecies transmission and genetic recombination which greatly increase diversity and complicate attempts at a unified and comprehensive classification strategy.",2017 May 10,"['Donato, Celeste', 'Vijaykrishna, Dhanasekaran']",Viruses,,,True
4b382dd30271d1544237000616b02988687c4402,PMC,Nasal Infection of Enterovirus D68 Leading to Lower Respiratory Tract Pathogenesis in Ferrets (Mustela putorius furo),http://dx.doi.org/10.3390/v9050104,PMC5454417,28489053,CC BY,"Data from EV-D68-infected patients demonstrate that pathological changes in the lower respiratory tract are principally characterized by severe respiratory illness in children and acute flaccid myelitis. However, lack of a suitable animal model for EV-D68 infection has limited the study on the pathogenesis of this critical pathogen, and the development of a vaccine. Ferrets have been widely used to evaluate respiratory virus infections. In the current study, we used EV-D68-infected ferrets as a potential animal to identify impersonal indices, involving clinical features and histopathological changes in the upper and lower respiratory tract (URT and LRT). The research results demonstrate that the EV-D68 virus leads to minimal clinical symptoms in ferrets. According to the viral load detection in the feces, nasal, and respiratory tracts, the infection and shedding of EV-D68 in the ferret model was confirmed, and these results were supported by the EV-D68 VP1 immunofluorescence confocal imaging with α2,6-linked sialic acid (SA) in lung tissues. Furthermore, we detected the inflammatory cytokine/chemokine expression level, which implied high expression levels of interleukin (IL)-1a, IL-8, IL-5, IL-12, IL-13, and IL-17a in the lungs. These data indicate that systemic observation of responses following infection with EV-D68 in ferrets could be used as a model for EV-D68 infection and pathogenesis.",2017 May 10,"['Zheng, Hui-Wen', 'Sun, Ming', 'Guo, Lei', 'Wang, Jing-Jing', 'Song, Jie', 'Li, Jia-Qi', 'Li, Hong-Zhe', 'Ning, Ruo-Tong', 'Yang, Ze-Ning', 'Fan, Hai-Tao', 'He, Zhan-Long', 'Liu, Long-Ding']",Viruses,,,True
671c27164c5c9dea34b515b57bddbb08e82ffb22,PMC,Nasal Infection of Enterovirus D68 Leading to Lower Respiratory Tract Pathogenesis in Ferrets (Mustela putorius furo),http://dx.doi.org/10.3390/v9050104,PMC5454417,28489053,CC BY,"Data from EV-D68-infected patients demonstrate that pathological changes in the lower respiratory tract are principally characterized by severe respiratory illness in children and acute flaccid myelitis. However, lack of a suitable animal model for EV-D68 infection has limited the study on the pathogenesis of this critical pathogen, and the development of a vaccine. Ferrets have been widely used to evaluate respiratory virus infections. In the current study, we used EV-D68-infected ferrets as a potential animal to identify impersonal indices, involving clinical features and histopathological changes in the upper and lower respiratory tract (URT and LRT). The research results demonstrate that the EV-D68 virus leads to minimal clinical symptoms in ferrets. According to the viral load detection in the feces, nasal, and respiratory tracts, the infection and shedding of EV-D68 in the ferret model was confirmed, and these results were supported by the EV-D68 VP1 immunofluorescence confocal imaging with α2,6-linked sialic acid (SA) in lung tissues. Furthermore, we detected the inflammatory cytokine/chemokine expression level, which implied high expression levels of interleukin (IL)-1a, IL-8, IL-5, IL-12, IL-13, and IL-17a in the lungs. These data indicate that systemic observation of responses following infection with EV-D68 in ferrets could be used as a model for EV-D68 infection and pathogenesis.",2017 May 10,"['Zheng, Hui-Wen', 'Sun, Ming', 'Guo, Lei', 'Wang, Jing-Jing', 'Song, Jie', 'Li, Jia-Qi', 'Li, Hong-Zhe', 'Ning, Ruo-Tong', 'Yang, Ze-Ning', 'Fan, Hai-Tao', 'He, Zhan-Long', 'Liu, Long-Ding']",Viruses,,,False
7d4b0efca3cb904640b8fd489fdfc413a8fae264,PMC,TMPRSS2 and MSPL Facilitate Trypsin-Independent Porcine Epidemic Diarrhea Virus Replication in Vero Cells,http://dx.doi.org/10.3390/v9050114,PMC5454426,28524070,CC BY,"Type II transmembrane serine proteases (TTSPs) facilitate the spread and replication of viruses such as influenza and human coronaviruses, although it remains unclear whether TTSPs play a role in the progression of animal coronavirus infections, such as that by porcine epidemic diarrhea virus (PEDV). In this study, TTSPs including TMPRSS2, HAT, DESC1, and MSPL were tested for their ability to facilitate PEDV replication in Vero cells. Our results showed that TMPRSS2 and MSPL played significant roles in the stages of cell–cell fusion and virus–cell fusion, whereas HAT and DESC1 exhibited weaker effects. This activation may be involved in the interaction between TTSPs and the PEDV S protein, as the S protein extensively co-localized with TMPRSS2 and MSPL and could be cleaved by co-expression with TMPRSS2 or MSPL. Moreover, the use of Vero cells expressing TMPRSS2 and MSPL facilitated PEDV replication in the absence of exogenous trypsin. In sum, we identified two host proteases, TMPRSS2 and MSPL, which may provide insights and a novel method for enhancing viral titers, expanding virus production, and improving the adaptability of PEDV isolates in vitro.",2017 May 18,"['Shi, Wen', 'Fan, Wenlu', 'Bai, Jing', 'Tang, Yandong', 'Wang, Li', 'Jiang, Yanping', 'Tang, Lijie', 'Liu, Min', 'Cui, Wen', 'Xu, Yigang', 'Li, Yijing']",Viruses,,,True
569f5c13c3109817f6ce0882e4129f31e83cfd29,PMC,Evaluation and Comparison of the Pathogenicity and Host Immune Responses Induced by a G2b Taiwan Porcine Epidemic Diarrhea Virus (Strain Pintung 52) and Its Highly Cell-Culture Passaged Strain in Conventional 5-Week-Old Pigs,http://dx.doi.org/10.3390/v9050121,PMC5454433,28534849,CC BY,"A genogroup 2b (G2b) porcine epidemic diarrhea virus (PEDV) Taiwan Pintung 52 (PEDVPT) strain was isolated in 2014. The pathogenicity and host antibody responses elicited by low-passage (passage 5; PEDVPT-P5) and high-passage (passage 96; PEDVPT-P96) PEDVPT strains were compared in post-weaning PEDV-seronegative pigs by oral inoculation. PEDVPT-P5-inoculation induced typical diarrhea during 1–9 days post inoculation with fecal viral shedding persisting for 26 days. Compared to PEDVPT-P5, PEDVPT-P96 inoculation induced none-to-mild diarrhea and lower, delayed fecal viral shedding. Although PEDVPT-P96 elicited slightly lower neutralizing antibodies and PEDV-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) titers, a reduction in pathogenicity and viral shedding of the subsequent challenge with PEDVPT-P5 were noted in both PEDVPT-P5- and PEDVPT-P96-inoculated pigs. Alignment and comparison of full-length sequences of PEDVPT-P5 and PEDVPT-P96 revealed 23 nucleotide changes and resultant 19 amino acid substitutions in non-structure proteins 2, 3, 4, 9, 14, 15, spike, open reading frame 3 (ORF3), and membrane proteins with no detectable deletion or insertion. The present study confirmed the pathogenicity of the PEDVPT isolate in conventional post-weaning pigs. Moreover, data regarding viral attenuation and potency of induced antibodies against PEDVPT-P5 identified PEDVPT-P96 as a potential live-attenuated vaccine candidate.",2017 May 19,"['Chang, Yen-Chen', 'Kao, Chi-Fei', 'Chang, Chia-Yu', 'Jeng, Chian-Ren', 'Tsai, Pei-Shiue', 'Pang, Victor Fei', 'Chiou, Hue-Ying', 'Peng, Ju-Yi', 'Cheng, Ivan-Chen', 'Chang, Hui-Wen']",Viruses,,,True
0d33d89c32913354f7164225a906ff85339293e2,PMC,Immunobiology of Newcastle Disease Virus and Its Use for Prophylactic Vaccination in Poultry and as Adjuvant for Therapeutic Vaccination in Cancer Patients,http://dx.doi.org/10.3390/ijms18051103,PMC5455011,28531117,CC BY,"Newcastle disease (ND) is one of the most important diseases of poultry worldwide. In the last decades, molecular research has gained a lot of new information about its causative agent, newcastle disease virus (NDV). In poultry industry, certain strains of NDV have been used for preventive vaccination for more than 60 years. NDV has also been applied to cancer patients with beneficial effects for about 50 years, but this is less well known. The molecular basis for these differential effects of NDV in birds and man have been elucidated in the last decades and are explained in this review. The anti-neoplastic and immune-stimulatory properties in non-permissive hosts such as mouse and man have to do with the strong type I interferon responses induced in these foreign species. Additionally, NDV has the potential to break various types of tumor resistances and also to affect liver fibrosis. A main section is devoted to the benefits of clinical application of NDV and NDV-based vaccines to cancer patients. Reverse genetics technology allowed developing NDV into a vector suitable for gene therapy. Examples will be provided in which genetically engineered NDV is being used successfully as vector against new emerging viruses.",2017 May 20,"Schirrmacher, Volker",Int J Mol Sci,,,True
b460e5b511b4e2c3233f9476cd4e0616d6f405ac,PMC,Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses,http://dx.doi.org/10.1371/journal.pone.0178408,PMC5456070,28575086,CC BY,"The severity of respiratory viral infections is partially determined by the cellular response mounted by infected lung epithelial cells. Disease prevention and treatment is dependent on our understanding of the shared and unique responses elicited by diverse viruses, yet few studies compare host responses to viruses from different families while controlling other experimental parameters. Murine models are commonly used to study the pathogenesis of respiratory viral infections, and in vitro studies using murine cells provide mechanistic insight into the pathogenesis observed in vivo. We used microarray analysis to compare changes in gene expression of murine lung epithelial cells infected individually by three respiratory viruses causing mild (rhinovirus, RV1B), moderate (coronavirus, MHV-1), and severe (influenza A virus, PR8) disease in mice. RV1B infection caused numerous gene expression changes, but the differential effect peaked at 12 hours post-infection. PR8 altered an intermediate number of genes whose expression continued to change through 24 hours. MHV-1 had comparatively few effects on host gene expression. The viruses elicited highly overlapping responses in antiviral genes, though MHV-1 induced a lower type I interferon response than the other two viruses. Signature genes were identified for each virus and included host defense genes for PR8, tissue remodeling genes for RV1B, and transcription factors for MHV-1. Our comparative approach identified universal and specific transcriptional signatures of virus infection that can be used to distinguish shared and virus-specific mechanisms of pathogenesis in the respiratory tract.",2017 Jun 2,"['VanLeuven, James T.', 'Ridenhour, Benjamin J.', 'Gonzalez, Andres J.', 'Miller, Craig R.', 'Miura, Tanya A.']",PLoS One,,,True
fce0c75ec68185c94d784620511fb5cdced9c0ec,PMC,Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses,http://dx.doi.org/10.1371/journal.pone.0178408,PMC5456070,28575086,CC BY,"The severity of respiratory viral infections is partially determined by the cellular response mounted by infected lung epithelial cells. Disease prevention and treatment is dependent on our understanding of the shared and unique responses elicited by diverse viruses, yet few studies compare host responses to viruses from different families while controlling other experimental parameters. Murine models are commonly used to study the pathogenesis of respiratory viral infections, and in vitro studies using murine cells provide mechanistic insight into the pathogenesis observed in vivo. We used microarray analysis to compare changes in gene expression of murine lung epithelial cells infected individually by three respiratory viruses causing mild (rhinovirus, RV1B), moderate (coronavirus, MHV-1), and severe (influenza A virus, PR8) disease in mice. RV1B infection caused numerous gene expression changes, but the differential effect peaked at 12 hours post-infection. PR8 altered an intermediate number of genes whose expression continued to change through 24 hours. MHV-1 had comparatively few effects on host gene expression. The viruses elicited highly overlapping responses in antiviral genes, though MHV-1 induced a lower type I interferon response than the other two viruses. Signature genes were identified for each virus and included host defense genes for PR8, tissue remodeling genes for RV1B, and transcription factors for MHV-1. Our comparative approach identified universal and specific transcriptional signatures of virus infection that can be used to distinguish shared and virus-specific mechanisms of pathogenesis in the respiratory tract.",2017 Jun 2,"['VanLeuven, James T.', 'Ridenhour, Benjamin J.', 'Gonzalez, Andres J.', 'Miller, Craig R.', 'Miura, Tanya A.']",PLoS One,,,False
cbd966ad23d27df95cf1959ae5d944fb363de366,PMC,Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses,http://dx.doi.org/10.1371/journal.pone.0178408,PMC5456070,28575086,CC BY,"The severity of respiratory viral infections is partially determined by the cellular response mounted by infected lung epithelial cells. Disease prevention and treatment is dependent on our understanding of the shared and unique responses elicited by diverse viruses, yet few studies compare host responses to viruses from different families while controlling other experimental parameters. Murine models are commonly used to study the pathogenesis of respiratory viral infections, and in vitro studies using murine cells provide mechanistic insight into the pathogenesis observed in vivo. We used microarray analysis to compare changes in gene expression of murine lung epithelial cells infected individually by three respiratory viruses causing mild (rhinovirus, RV1B), moderate (coronavirus, MHV-1), and severe (influenza A virus, PR8) disease in mice. RV1B infection caused numerous gene expression changes, but the differential effect peaked at 12 hours post-infection. PR8 altered an intermediate number of genes whose expression continued to change through 24 hours. MHV-1 had comparatively few effects on host gene expression. The viruses elicited highly overlapping responses in antiviral genes, though MHV-1 induced a lower type I interferon response than the other two viruses. Signature genes were identified for each virus and included host defense genes for PR8, tissue remodeling genes for RV1B, and transcription factors for MHV-1. Our comparative approach identified universal and specific transcriptional signatures of virus infection that can be used to distinguish shared and virus-specific mechanisms of pathogenesis in the respiratory tract.",2017 Jun 2,"['VanLeuven, James T.', 'Ridenhour, Benjamin J.', 'Gonzalez, Andres J.', 'Miller, Craig R.', 'Miura, Tanya A.']",PLoS One,,,False
9bd6e6fa5a11670fc184f642a89e3c665f3d5bd3,PMC,Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses,http://dx.doi.org/10.1371/journal.pone.0178408,PMC5456070,28575086,CC BY,"The severity of respiratory viral infections is partially determined by the cellular response mounted by infected lung epithelial cells. Disease prevention and treatment is dependent on our understanding of the shared and unique responses elicited by diverse viruses, yet few studies compare host responses to viruses from different families while controlling other experimental parameters. Murine models are commonly used to study the pathogenesis of respiratory viral infections, and in vitro studies using murine cells provide mechanistic insight into the pathogenesis observed in vivo. We used microarray analysis to compare changes in gene expression of murine lung epithelial cells infected individually by three respiratory viruses causing mild (rhinovirus, RV1B), moderate (coronavirus, MHV-1), and severe (influenza A virus, PR8) disease in mice. RV1B infection caused numerous gene expression changes, but the differential effect peaked at 12 hours post-infection. PR8 altered an intermediate number of genes whose expression continued to change through 24 hours. MHV-1 had comparatively few effects on host gene expression. The viruses elicited highly overlapping responses in antiviral genes, though MHV-1 induced a lower type I interferon response than the other two viruses. Signature genes were identified for each virus and included host defense genes for PR8, tissue remodeling genes for RV1B, and transcription factors for MHV-1. Our comparative approach identified universal and specific transcriptional signatures of virus infection that can be used to distinguish shared and virus-specific mechanisms of pathogenesis in the respiratory tract.",2017 Jun 2,"['VanLeuven, James T.', 'Ridenhour, Benjamin J.', 'Gonzalez, Andres J.', 'Miller, Craig R.', 'Miura, Tanya A.']",PLoS One,,,False
f19f2b01d3520c10962617e9f078ff9a5a850c88,PMC,The outcomes and controversies of transplant tourism—Lessons of an 11-year retrospective cohort study from Taiwan,http://dx.doi.org/10.1371/journal.pone.0178569,PMC5456093,28575014,CC BY,"BACKGROUND: Transplant tourism has increased rapidly in the past two decades, accounting for about 10% of world organ transplants. However it is ethically controversial and discouraged by professional guidelines. We conducted this study to investigate the outcomes and trends of overseas kidney and liver transplantation in Taiwan to provide a sound basis for ethical reflection. METHODS AND FINDINGS: The Taiwanese National Health Insurance Research Database was used to identify 2381 domestic and 2518 overseas kidney transplant (KT) recipients from 1998 to 2009 and 1758 domestic and 540 overseas liver transplantation (LT) recipients from 1999 to 2009. Cox proportional hazards models were used to assess the risks of mortality and graft failure. The numbers of overseas transplantation increased after 2000, reached a peak in 2005 and decreased after 2007. Compared to their domestic counterparts, the overseas KT recipients were older, male predominant, with shorter pre-op dialysis period and more comorbidities. Similarly, the overseas LT recipients were older, male predominant and had more hepatocellular carcinoma cases. The 1-, 5-, and 10-year patient survival rates were 96.9%, 91.7% and 83.0% respectively for domestic KT and 95.8%, 87.8% and 73.1% for overseas KT (p<0.001). The 1-, 5-, and 10-year patient survival rates were 89.2%, 79.5%, 75.2% for domestic LT and 79.8%, 54.7%, 49.9% for overseas LT (p<0.001). CONCLUSION: The poorer outcomes of the overseas groups may be due to more older patients, more comorbidities (KT), or more hepatocellular carcinoma recurrences (LT). After domestic reform and international ethical challenges, the numbers of organ tourism decreased but the practice still persisted surreptitiously. Compulsory registration policies for overseas transplantation with international conventions to sanction organ trafficking and transplant tourism should be considered to stop these controversial practices.",2017 Jun 2,"['Tsai, Daniel Fu-Chang', 'Huang, Shi-Wei', 'Holm, Soren', 'Lin, Yi-Ping', 'Chang, Yu-Kang', 'Hsu, Chih-Cheng']",PLoS One,,,True
51a9c29256613695c56f498f3d601a921de0079b,PMC,The outcomes and controversies of transplant tourism—Lessons of an 11-year retrospective cohort study from Taiwan,http://dx.doi.org/10.1371/journal.pone.0178569,PMC5456093,28575014,CC BY,"BACKGROUND: Transplant tourism has increased rapidly in the past two decades, accounting for about 10% of world organ transplants. However it is ethically controversial and discouraged by professional guidelines. We conducted this study to investigate the outcomes and trends of overseas kidney and liver transplantation in Taiwan to provide a sound basis for ethical reflection. METHODS AND FINDINGS: The Taiwanese National Health Insurance Research Database was used to identify 2381 domestic and 2518 overseas kidney transplant (KT) recipients from 1998 to 2009 and 1758 domestic and 540 overseas liver transplantation (LT) recipients from 1999 to 2009. Cox proportional hazards models were used to assess the risks of mortality and graft failure. The numbers of overseas transplantation increased after 2000, reached a peak in 2005 and decreased after 2007. Compared to their domestic counterparts, the overseas KT recipients were older, male predominant, with shorter pre-op dialysis period and more comorbidities. Similarly, the overseas LT recipients were older, male predominant and had more hepatocellular carcinoma cases. The 1-, 5-, and 10-year patient survival rates were 96.9%, 91.7% and 83.0% respectively for domestic KT and 95.8%, 87.8% and 73.1% for overseas KT (p<0.001). The 1-, 5-, and 10-year patient survival rates were 89.2%, 79.5%, 75.2% for domestic LT and 79.8%, 54.7%, 49.9% for overseas LT (p<0.001). CONCLUSION: The poorer outcomes of the overseas groups may be due to more older patients, more comorbidities (KT), or more hepatocellular carcinoma recurrences (LT). After domestic reform and international ethical challenges, the numbers of organ tourism decreased but the practice still persisted surreptitiously. Compulsory registration policies for overseas transplantation with international conventions to sanction organ trafficking and transplant tourism should be considered to stop these controversial practices.",2017 Jun 2,"['Tsai, Daniel Fu-Chang', 'Huang, Shi-Wei', 'Holm, Soren', 'Lin, Yi-Ping', 'Chang, Yu-Kang', 'Hsu, Chih-Cheng']",PLoS One,,,False
621fc53e298c0a2dc4e8c6c871fcd8cca0e707e8,PMC,Distribution and Evolutionary History of the Mobile Genetic Element s2m in Coronaviruses,http://dx.doi.org/10.3390/diseases4030027,PMC5456283,28933407,CC BY,"The mobile genetic element s2m has been described in several families of single-stranded RNA viruses. The function remains elusive, but an increasing number of s2m-containing sequences are being deposited in publicly available databases. Currently, more than 700 coronavirus sequences containing s2m can be found in GenBank, including the severe acute respiratory syndrome (SARS) coronavirus genome. This is an updated review of the pattern of s2m in coronaviruses, the possible functional implications and the evolutionary history.",2016 Jul 28,"['Tengs, Torstein', 'Jonassen, Christine M.']",Diseases,,,True
30abdf7a423427b001aee5d319abecfb5ad1671b,PMC,Human Coronaviruses: A Review of Virus–Host Interactions,http://dx.doi.org/10.3390/diseases4030026,PMC5456285,28933406,CC BY,"Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory outcomes. In the past 14 years, the onset of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans. The study of HCoV-host interactions has contributed extensively to our understanding of HCoV pathogenesis. In this review, we discuss some of the recent findings of host cell factors that might be exploited by HCoVs to facilitate their own replication cycle. We also discuss various cellular processes, such as apoptosis, innate immunity, ER stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs.",2016 Jul 25,"['Lim, Yvonne Xinyi', 'Ng, Yan Ling', 'Tam, James P.', 'Liu, Ding Xiang']",Diseases,,,True
fc7e5ad5354977c8df7a4dfa7ffe37eed76a975f,PMC,"Detection of Alphacoronavirus vRNA in the Feces of Brazilian Free-Tailed Bats (Tadarida brasiliensis) from a Colony in Florida, USA",http://dx.doi.org/10.3390/diseases5010007,PMC5456339,28933360,CC BY,"Bats are natural reservoirs of coronaviruses and other viruses with zoonotic potential. Florida has indigenous non-migratory populations of Brazilian free-tailed bats (Tadarida brasiliensis) that mostly roost in colonies in artificial structures. Unlike their counterparts in Brazil and Mexico, the viruses harbored by the Florida bats have been underexplored. We report the detection of an alphacoronavirus RNA-dependent RNA polymerase (RdRp) gene sequence in the feces of two of 19 different T. brasiliensis that were capture/release bats that had been evaluated for overall health. The RdRp sequence is similar but not identical to previously detected sequences in the feces of two different species of bats (T. brasiliensis and Molossus molossus) in Brazil. In common with the experience of others doing similar work, attempts to isolate the virus in cell cultures were unsuccessful. We surmise that this and highly related alphacoronavirus are carried by Brazilian free-tailed bats living in a wide eco-spatial region. As various coronaviruses (CoVs) that affect humans emerged from bats, our study raises the question whether CoVs such as the one detected in our work are yet-to-be-detected pathogens of humans and animals other than bats.",2017 Feb 27,"['Bonny, Tania S.', 'Driver, John P.', 'Paisie, Taylor', 'Salemi, Marco', 'Morris, John Glenn', 'Shender, Lisa A.', 'Smith, Lisa', 'Enloe, Carolyn', 'Oxenrider, Kevin', 'Gore, Jeffery A.', 'Loeb, Julia C.', 'Wu, Chang-Yu', 'Lednicky, John A.']",Diseases,,,True
b57881ebdcf26fc2a0c3f95932be71e881212f76,PMC,Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis,http://dx.doi.org/10.1155/2017/1359064,PMC5457781,28607531,CC BY,"The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6) at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver.",2017 May 4,"['Carrière, Virginie', 'Arshad, Muhammad Imran', 'Le Seyec, Jacques', 'Lefevre, Benjamin', 'Farooq, Muhammad', 'Jan, Aurélien', 'Manuel, Christelle', 'Touami-Bernard, Laurence', 'Lucas-Clerc, Catherine', 'Genet, Valentine', 'Gascan, Hugues', 'Girard, Jean-Philippe', 'Chalmel, Frédéric', 'Lamontagne, Lucie', 'Piquet-Pellorce, Claire', 'Samson, Michel']",Mediators Inflamm,,,False
bb61dcfd20c7d56e90a52779d3f51a1f68c46362,PMC,Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis,http://dx.doi.org/10.1155/2017/1359064,PMC5457781,28607531,CC BY,"The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6) at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver.",2017 May 4,"['Carrière, Virginie', 'Arshad, Muhammad Imran', 'Le Seyec, Jacques', 'Lefevre, Benjamin', 'Farooq, Muhammad', 'Jan, Aurélien', 'Manuel, Christelle', 'Touami-Bernard, Laurence', 'Lucas-Clerc, Catherine', 'Genet, Valentine', 'Gascan, Hugues', 'Girard, Jean-Philippe', 'Chalmel, Frédéric', 'Lamontagne, Lucie', 'Piquet-Pellorce, Claire', 'Samson, Michel']",Mediators Inflamm,,,True
8b38aa40712b9033fb9a8c29c35e26aecc0e8a28,PMC,miR‐127‐5p negatively regulates enterovirus 71 replication by directly targeting SCARB2,http://dx.doi.org/10.1002/2211-5463.12197,PMC5458453,28593131,CC BY,"Enterovirus 71 (EV71) is the major causative agent of hand‐foot‐and‐mouth disease in young children and can cause severe cerebral and pulmonary complications and even fatality. This study aimed at elucidating whether and how EV71 infection is regulated by a cellular microRNA, miR‐127‐5p. We found that miR‐127‐5p can downregulate the expression of SCARB2, a main receptor of EV71, by targeting two potential sites in its 3′ UTR region and inhibit EV71 infection. Meanwhile, miR‐127‐5p expression was upregulated during EV71 infection. Notably, transfecting cells with miR‐127‐5p mimics led to a significant decrease in viral replication, while inhibition of endogenous miR‐127‐5p facilitated viral replication. Furthermore, our evidence showed that miR‐127‐5p did not affect postentry viral replication. Taken together, these results indicated that miR‐127‐5p inhibited EV71 replication by targeting the SCARB2 mRNA.",2017 Apr 13,"['Feng, Chunhong', 'Fu, Yuxuan', 'Chen, Deyan', 'Wang, Huanru', 'Su, Airong', 'Zhang, Li', 'Chang, Liang', 'Zheng, Nan', 'Wu, Zhiwei']",FEBS Open Bio,,,True
9b1ed09206bdc3bc05e88bd694bf863dbd1f973b,PMC,A Four-Biomarker Blood Signature Discriminates Systemic Inflammation Due to Viral Infection Versus Other Etiologies,http://dx.doi.org/10.1038/s41598-017-02325-8,PMC5460227,28588308,CC BY,"The innate immune system of humans and other mammals responds to pathogen-associated molecular patterns (PAMPs) that are conserved across broad classes of infectious agents such as bacteria and viruses. We hypothesized that a blood-based transcriptional signature could be discovered indicating a host systemic response to viral infection. Previous work identified host transcriptional signatures to individual viruses including influenza, respiratory syncytial virus and dengue, but the generality of these signatures across all viral infection types has not been established. Based on 44 publicly available datasets and two clinical studies of our own design, we discovered and validated a four-gene expression signature in whole blood, indicative of a general host systemic response to many types of viral infection. The signature’s genes are: Interferon Stimulated Gene 15 (ISG15), Interleukin 16 (IL16), 2′,5′-Oligoadenylate Synthetase Like (OASL), and Adhesion G Protein Coupled Receptor E5 (ADGRE5). In each of 13 validation datasets encompassing human, macaque, chimpanzee, pig, mouse, rat and all seven Baltimore virus classification groups, the signature provides statistically significant (p < 0.05) discrimination between viral and non-viral conditions. The signature may have clinical utility for differentiating host systemic inflammation (SI) due to viral versus bacterial or non-infectious causes.",2017 Jun 6,"['Sampson, D. L.', 'Fox, B. A.', 'Yager, T. D.', 'Bhide, S.', 'Cermelli, S.', 'McHugh, L. C.', 'Seldon, T. A.', 'Brandon, R. A.', 'Sullivan, E.', 'Zimmerman, J. J.', 'Noursadeghi, M.', 'Brandon, R. B.']",Sci Rep,,,True
e88057a7b0014a7c9fc085a0e9d8b53b71886829,PMC,A Four-Biomarker Blood Signature Discriminates Systemic Inflammation Due to Viral Infection Versus Other Etiologies,http://dx.doi.org/10.1038/s41598-017-02325-8,PMC5460227,28588308,CC BY,"The innate immune system of humans and other mammals responds to pathogen-associated molecular patterns (PAMPs) that are conserved across broad classes of infectious agents such as bacteria and viruses. We hypothesized that a blood-based transcriptional signature could be discovered indicating a host systemic response to viral infection. Previous work identified host transcriptional signatures to individual viruses including influenza, respiratory syncytial virus and dengue, but the generality of these signatures across all viral infection types has not been established. Based on 44 publicly available datasets and two clinical studies of our own design, we discovered and validated a four-gene expression signature in whole blood, indicative of a general host systemic response to many types of viral infection. The signature’s genes are: Interferon Stimulated Gene 15 (ISG15), Interleukin 16 (IL16), 2′,5′-Oligoadenylate Synthetase Like (OASL), and Adhesion G Protein Coupled Receptor E5 (ADGRE5). In each of 13 validation datasets encompassing human, macaque, chimpanzee, pig, mouse, rat and all seven Baltimore virus classification groups, the signature provides statistically significant (p < 0.05) discrimination between viral and non-viral conditions. The signature may have clinical utility for differentiating host systemic inflammation (SI) due to viral versus bacterial or non-infectious causes.",2017 Jun 6,"['Sampson, D. L.', 'Fox, B. A.', 'Yager, T. D.', 'Bhide, S.', 'Cermelli, S.', 'McHugh, L. C.', 'Seldon, T. A.', 'Brandon, R. A.', 'Sullivan, E.', 'Zimmerman, J. J.', 'Noursadeghi, M.', 'Brandon, R. B.']",Sci Rep,,,True
eccdf56c0564f35ba8e293bfd967e98b822bfef2,PMC,Translational Rodent Models for Research on Parasitic Protozoa—A Review of Confounders and Possibilities,http://dx.doi.org/10.3389/fcimb.2017.00238,PMC5461347,28638807,CC BY,"Rodents, in particular Mus musculus, have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases. We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results. Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice. We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments. Frequently, mouse or rat models are chosen for convenience, e.g., availability in the institution rather than on an unbiased evaluation of whether they provide the answer to a given question. Apart from a general discussion on translational success or failure, we provide examples where infections with single-celled parasites in a chosen lab rodent gave contradictory or misleading results, and when possible discuss the reason for this. We present emerging alternatives to traditional rodent models, such as humanized mice and organoid primary cell cultures. So-called recombinant inbred strains such as the Collaborative Cross collection are also a potential solution for certain challenges. In addition, we emphasize the advantages of using wild rodents for certain immunological, ecological, and/or behavioral questions. The experimental challenges (e.g., availability of species-specific reagents) that come with the use of such non-model systems are also discussed. Our intention is to foster critical judgment of both traditional and newly available translational rodent models for research on parasitic protozoa that can complement the existing mouse and rat models.",2017 Jun 7,"['Ehret, Totta', 'Torelli, Francesca', 'Klotz, Christian', 'Pedersen, Amy B.', 'Seeber, Frank']",Front Cell Infect Microbiol,,,True
e9c7ab1074e8ce62dbab3300ed0cb5babd980e69,PMC,Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases,http://dx.doi.org/10.1002/prp2.293,PMC5461643,28596841,CC BY,"Emerging viruses such as HIV, dengue, influenza A, SARS coronavirus, Ebola, and other viruses pose a significant threat to human health. Majority of these viruses are responsible for the outbreaks of pathogenic lethal infections. To date, there are no effective therapeutic strategies available for the prophylaxis and treatment of these infections. Chloroquine analogs have been used for decades as the primary and most successful drugs against malaria. Concomitant with the emergence of chloroquine‐resistant Plasmodium strains and a subsequent decrease in the use as antimalarial drugs, other applications of the analogs have been investigated. Since the analogs have interesting biochemical properties, these drugs are found to be effective against a wide variety of viral infections. As antiviral action, the analogs have been shown to inhibit acidification of endosome during the events of replication and infection. Moreover, immunomodulatory effects of analogs have been beneficial to patients with severe inflammatory complications of several viral diseases. Interestingly, one of the successful targeting strategies is the inhibition of HIV replication by the analogs in vitro which are being tested in several clinical trials. This review focuses on the potentialities of chloroquine analogs for the treatment of endosomal low pH dependent emerging viral diseases.",2017 Jan 23,"Al‐Bari, Md. Abdul Alim",Pharmacol Res Perspect,,,True
f8efe7295a7cf875c8a695df3e87a42e651ce60d,PMC,Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana,http://dx.doi.org/10.1186/s12889-017-4474-6,PMC5461762,28587602,CC BY,"BACKGROUND: The recent Ebola Virus Disease (EVD) epidemic that hit some countries in West Africa underscores the need to train front line high-risk health workers on disease prevention skills. Although Ghana did not record (and is yet to) any case, and several health workers have received numerous training schemes, there is no record of any study that assessed preparedness of healthcare workers (HCWS) regarding EVD and any emergency prone disease in Ghana. We therefore conducted a hospital based cross sectional study involving 101 HCWs from two facilities in Kumasi, Ghana to assess the level of preparedness of HCWs to respond to any possible EVD. METHODS: We administered a face-to-face questionnaire using an adapted WHO (2015) and CDC (2014) Checklist for Ebola Preparedness and assessed overall knowledge gaps, and preparedness of the Ghanaian HCWs in selected health facilities of the Ashanti Region of Ghana from October to December 2015. RESULTS: A total 92 (91.09%) HCWs indicated they were not adequately trained to handle an EVD suspected case. Only 25.74% (n = 26) considered their facilities sufficiently equipped to handle and manage EVD patients. When asked which disinfectant to use after attending to and caring for a suspected patient with EVD, only 8.91% (n = 9) could correctly identify the right disinfectant (χ(2) = 28.52, p = 0.001). CONCLUSION: Our study demonstrates poor knowledge and ill preparedness and unwillingness of many HCWs to attend to EVD. Beyond knowledge acquisition, there is the need for more training from time to time to fully prepare HCWs to handle any possible EVD case.",2017 Jun 6,"['Annan, Augustina Angelina', 'Yar, Denis Dekugmen', 'Owusu, Michael', 'Biney, Eno Akua', 'Forson, Paa Kobina', 'Okyere, Portia Boakye', 'Gyimah, Akosua Adumea', 'Owusu-Dabo, Ellis']",BMC Public Health,,,True
72ace5af731fdf4c384e912b074193d13902b7a1,PMC,Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1186/1471-2172-6-2,PMC546205,15655079,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS) emerged in later February 2003, as a new epidemic form of life-threatening infection caused by a novel coronavirus. However, the immune-pathogenesis of SARS is poorly understood. To understand the host response to this pathogen, we investigated the gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from SARS patients, and compared with healthy controls. RESULTS: The number of differentially expressed genes was found to be 186 under stringent filtering criteria of microarray data analysis. Several genes were highly up-regulated in patients with SARS, such as, the genes coding for Lactoferrin, S100A9 and Lipocalin 2. The real-time PCR method verified the results of the gene array analysis and showed that those genes that were up-regulated as determined by microarray analysis were also found to be comparatively up-regulated by real-time PCR analysis. CONCLUSIONS: This differential gene expression profiling of PBMCs from patients with SARS strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response, rather than a specific immune response against a viral infection, as we observed a complete lack of cytokine genes usually triggered during a viral infection. Our study shows for the first time how the immune system responds to the SARS infection, and opens new possibilities for designing new diagnostics and treatments for this new life-threatening disease.",2005 Jan 18,"['Reghunathan, Renji', 'Jayapal, Manikandan', 'Hsu, Li-Yang', 'Chng, Hiok-Hee', 'Tai, Dessmon', 'Leung, Bernard P', 'Melendez, Alirio J']",BMC Immunol,,,True
7dd0d85115b61c06ca2cfc389b6dfd2517708011,PMC,Frequency of respiratory virus infections and next-generation analysis of influenza A/H1N1pdm09 dynamics in the lower respiratory tract of patients admitted to the ICU,http://dx.doi.org/10.1371/journal.pone.0178926,PMC5462403,28591230,CC BY,"Recent molecular diagnostic methods have significantly improved the diagnosis of viral pneumonia in intensive care units (ICUs). It has been observed that 222G/N changes in the HA gene of H1N1pdm09 are associated with increased lower respiratory tract (LRT) replication and worse clinical outcome. In the present study, the frequency of respiratory viruses was assessed in respiratory samples from 88 patients admitted to 16 ICUs during the 2014–2015 winter-spring season in Lombardy. Sixty-nine out of 88 (78.4%) patients were positive for a respiratory viral infection at admission. Of these, 57/69 (82.6%) were positive for influenza A (41 A/H1N1pdm09 and 15 A/H3N2), 8/69 (11.6%) for HRV, 2/69 (2.9%) for RSV and 2/69 (2.9%) for influenza B. Phylogenetic analysis of influenza A/H1N1pdm09 strains from 28/41 ICU-patients and 21 patients with mild respiratory syndrome not requiring hospitalization, showed the clear predominance of subgroup 6B strains. The median influenza A load in LRT samples of ICU patients was higher than that observed in the upper respiratory tract (URT) (p<0.05). Overall, a greater number of H1N1pdm09 virus variants were observed using next generation sequencing on partial HA sequences (codons 180–286) in clinical samples from the LRT as compared to URT. In addition, 222G/N/A mutations were observed in 30% of LRT samples from ICU patients. Finally, intra-host evolution analysis showed the presence of different dynamics of viral population in LRT of patients hospitalized in ICU with a severe influenza infection.",2017 Jun 7,"['Piralla, Antonio', 'Rovida, Francesca', 'Girello, Alessia', 'Premoli, Marta', 'Mojoli, Francesco', 'Belliato, Mirko', 'Braschi, Antonio', 'Iotti, Giorgio', 'Pariani, Elena', 'Bubba, Laura', 'Zanetti, Alessandro R.', 'Baldanti, Fausto']",PLoS One,,,True
756a222d5348e4c876a19dde4c0ffcb5b9c23db2,PMC,What is a Hotspot Anyway?,http://dx.doi.org/10.4269/ajtmh.16-0427,PMC5462559,28719289,CC BY,"The importance of spatial clusters, or “hotspots,” in infectious disease epidemiology has been increasingly recognized, and targeting hotspots is often seen as an important component of disease-control strategies. However, the precise meaning of “hotspot” varies widely in current research and policy documents. Hotspots have been variously described as areas of elevated incidence or prevalence, higher transmission efficiency or risk, or higher probability of disease emergence. This ambiguity has led to confusion and may result in mistaken inferences regarding the best way to target interventions. We surveyed the literature on epidemiologic hotspots, examining the multitude of ways in which the term is used; and highlight the difference in the geographic scale of hotspots and the properties they are supposed to have. In response to the diversity in the term's usage, we advocate the use of more precise terms, such as “burden hotspot,” “transmission hotspot,” and “emergence hotspot,” as well as explicit specification of the spatiotemporal scale of interest. Increased precision in terminology is needed to ensure clear and effective policies for disease control.",2017 Jun 7,"['Lessler, Justin', 'Azman, Andrew S.', 'McKay, Heather S.', 'Moore, Sean M.']",Am J Trop Med Hyg,,,True
03ca47766e6f3e8d5d71fa25d86803f82d690b38,PMC,Myricitrin Protects Cardiomyocytes from Hypoxia/Reoxygenation Injury: Involvement of Heat Shock Protein 90,http://dx.doi.org/10.3389/fphar.2017.00353,PMC5462924,28642708,CC BY,"Modulation of oxidative stress is therapeutically effective in ischemia/reperfusion (I/R) injury. Myricitrin, a naturally occurring phenolic compound, is a potent antioxidant. However, little is known about its effect on I/R injury to cardiac myocytes. The present study was performed to investigate the potential protective effect of myricitrin against hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocyte injury and its underlying mechanisms. Myricitrin pretreatment improved cardiomyocyte viability, inhibited ROS generation, maintained the mitochondrial membrane potential, reduced apoptotic cardiomyocytes, decreased the caspase-3 activity, upregulated antiapoptotic proteins and downregulated proapoptotic proteins during H/R injury. Moreover, the potential targets of myricitrin was predicted using Discovery Studio software, and heat shock protein 90 (Hsp90) was identified as the main disease-related target. Further mechanistic investigation revealed that 17-AAG, a pharmacologic inhibitor of Hsp90, significantly blocked the myricitrin-induced cardioprotective effect demonstrated by increased apoptosis and ROS generation. These results suggested that myricitrin provides protection to H9c2 cardiomyocytes against H/R-induced oxidative stress and apoptosis, most likely via increased expression of Hsp90.",2017 Jun 8,"['Wang, Min', 'Sun, Gui-bo', 'Du, Yu-yang', 'Tian, Yu', 'Liao, Ping', 'Liu, Xue-song', 'Ye, Jing-xue', 'Sun, Xiao-bo']",Front Pharmacol,,,True
e021441c02baaade6b2b93427db4beb54b06ea92,PMC,Infections Caused by HRSV A ON1 Are Predominant among Hospitalized Infants with Bronchiolitis in São Paulo City,http://dx.doi.org/10.1155/2017/3459785,PMC5463120,28626754,CC BY,"Human respiratory syncytial virus is the main cause of respiratory infections in infants. Several HRSV genotypes have been described. Goals. To describe the main genotypes that caused infections in São Paulo (2013–2015) and to analyze their clinical/epidemiological features. Methods. 94 infants (0–6 months) with bronchiolitis were studied. Clinical/epidemiological information was collected; a search for 16 viruses in nasopharyngeal secretion (PCR-real-time and conventional, sequencing, and phylogenetic analyses) was performed. Results. The mean age was 2.4 m; 48% were male. The mean length of hospital stay was 4.4 d (14% in the Intensive Care Unit). The positive rate of respiratory virus was 98.9%; 73 cases (77.6%) were HRSV (76,7% HRSVA). HRSVA formed three clusters: ON1 (n = 34), NA1 (n = 1), and NA2 (n = 4). All HRSVB were found to cluster in the BA genotype (BA9-n = 10; BA10-n = 3). Clinical analyses showed no significant differences between the genotype AON1 and other genotypes. Conclusion. This study showed a high rate of HRSV detection in bronchiolitis. HRSVA ON1, which has recently been described in other countries and has not been identified in previous studies in the southeast region of Brazil, was predominant. The clinical characteristics of the infants that were infected with AON1 were similar to infants with infections by other genotypes.",2017 May 24,"['Vieira, Sandra E.', 'Thomazelli, Luciano M.', 'de Paulis, Milena', 'Ferronato, Angela E.', 'Oliveira, Daniele B.', 'Martinez, Marina Baquerizo', 'Durigon, Edison L.']",Biomed Res Int,,,True
4c75ec78fc71ab06b4dd254cb8d8ad20de4bbc57,PMC,Severe varicella-zoster virus pneumonia: a multicenter cohort study,http://dx.doi.org/10.1186/s13054-017-1731-0,PMC5463395,28592328,CC BY,"BACKGROUND: Pneumonia is a dreaded complication of varicella-zoster virus (VZV) infection in adults; however, the data are limited. Our objective was to investigate the clinical features, management, and outcomes of critically ill patients with VZV-related community-acquired pneumonia (VZV-CAP). METHODS: This was an observational study of patients with VZV-CAP admitted to 29 intensive care units (ICUs) from January 1996 to January 2015. RESULTS: One hundred and two patients with VZV-CAP were included. Patients were young (age 39 years (interquartile range 32–51)) and 53 (52%) were immunocompromised. Time since respiratory symptom onset was 2 (1–3) days. There was a seasonal distribution of the disease, with more cases during spring and winter time. All but four patients presented with typical skin rash on ICU admission. Half the patients received mechanical ventilation within 1 (1–2) day following ICU admission (the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO(2)/FiO(2)) = 150 (80–284), 80% with acute respiratory distress syndrome (ARDS)). Sequential Organ Failure Assessment (SOFA) score on day 1 (odds ratio (OR) 1.90 (1.33–2.70); p < 0.001), oxygen flow at ICU admission (OR 1.25 (1.08–1.45); p = 0.004), and early bacterial co-infection (OR 14.94 (2.00–111.8); p = 0.009) were independently associated with the need for mechanical ventilation. Duration of mechanical ventilation was 14 (7–21) days. ICU and hospital mortality rates were 17% and 24%, respectively. All patients were treated with aciclovir and 10 received adjunctive therapy with steroids. Compared to 60 matched steroid-free controls, patients treated with steroids had a longer mechanical ventilation duration, ICU length of stay, and a similar hospital mortality, but experienced more ICU-acquired infections. CONCLUSIONS: Severe VZV-CAP is responsible for an acute pulmonary involvement associated with a significant morbidity and mortality. Steroid therapy did not influence mortality, but increased the risk of superinfection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-017-1731-0) contains supplementary material, which is available to authorized users.",2017 Jun 7,"['Mirouse, Adrien', 'Vignon, Philippe', 'Piron, Prescillia', 'Robert, René', 'Papazian, Laurent', 'Géri, Guillaume', 'Blanc, Pascal', 'Guitton, Christophe', 'Guérin, Claude', 'Bigé, Naïke', 'Rabbat, Antoine', 'Lefebvre, Aurélie', 'Razazi, Keyvan', 'Fartoukh, Muriel', 'Mariotte, Eric', 'Bouadma, Lila', 'Ricard, Jean-Damien', 'Seguin, Amélie', 'Souweine, Bertrand', 'Moreau, Anne-Sophie', 'Faguer, Stanislas', 'Mari, Arnaud', 'Mayaux, Julien', 'Schneider, Francis', 'Stoclin, Annabelle', 'Perez, Pierre', 'Maizel, Julien', 'Lafon, Charles', 'Ganster, Frédérique', 'Argaud, Laurent', 'Girault, Christophe', 'Barbier, François', 'Lecuyer, Lucien', 'Lambert, Jérôme', 'Canet, Emmanuel']",Crit Care,,,False
b0718d5c8888216c95fa19d7a79fd709da2c3ff4,PMC,Severe varicella-zoster virus pneumonia: a multicenter cohort study,http://dx.doi.org/10.1186/s13054-017-1731-0,PMC5463395,28592328,CC BY,"BACKGROUND: Pneumonia is a dreaded complication of varicella-zoster virus (VZV) infection in adults; however, the data are limited. Our objective was to investigate the clinical features, management, and outcomes of critically ill patients with VZV-related community-acquired pneumonia (VZV-CAP). METHODS: This was an observational study of patients with VZV-CAP admitted to 29 intensive care units (ICUs) from January 1996 to January 2015. RESULTS: One hundred and two patients with VZV-CAP were included. Patients were young (age 39 years (interquartile range 32–51)) and 53 (52%) were immunocompromised. Time since respiratory symptom onset was 2 (1–3) days. There was a seasonal distribution of the disease, with more cases during spring and winter time. All but four patients presented with typical skin rash on ICU admission. Half the patients received mechanical ventilation within 1 (1–2) day following ICU admission (the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO(2)/FiO(2)) = 150 (80–284), 80% with acute respiratory distress syndrome (ARDS)). Sequential Organ Failure Assessment (SOFA) score on day 1 (odds ratio (OR) 1.90 (1.33–2.70); p < 0.001), oxygen flow at ICU admission (OR 1.25 (1.08–1.45); p = 0.004), and early bacterial co-infection (OR 14.94 (2.00–111.8); p = 0.009) were independently associated with the need for mechanical ventilation. Duration of mechanical ventilation was 14 (7–21) days. ICU and hospital mortality rates were 17% and 24%, respectively. All patients were treated with aciclovir and 10 received adjunctive therapy with steroids. Compared to 60 matched steroid-free controls, patients treated with steroids had a longer mechanical ventilation duration, ICU length of stay, and a similar hospital mortality, but experienced more ICU-acquired infections. CONCLUSIONS: Severe VZV-CAP is responsible for an acute pulmonary involvement associated with a significant morbidity and mortality. Steroid therapy did not influence mortality, but increased the risk of superinfection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-017-1731-0) contains supplementary material, which is available to authorized users.",2017 Jun 7,"['Mirouse, Adrien', 'Vignon, Philippe', 'Piron, Prescillia', 'Robert, René', 'Papazian, Laurent', 'Géri, Guillaume', 'Blanc, Pascal', 'Guitton, Christophe', 'Guérin, Claude', 'Bigé, Naïke', 'Rabbat, Antoine', 'Lefebvre, Aurélie', 'Razazi, Keyvan', 'Fartoukh, Muriel', 'Mariotte, Eric', 'Bouadma, Lila', 'Ricard, Jean-Damien', 'Seguin, Amélie', 'Souweine, Bertrand', 'Moreau, Anne-Sophie', 'Faguer, Stanislas', 'Mari, Arnaud', 'Mayaux, Julien', 'Schneider, Francis', 'Stoclin, Annabelle', 'Perez, Pierre', 'Maizel, Julien', 'Lafon, Charles', 'Ganster, Frédérique', 'Argaud, Laurent', 'Girault, Christophe', 'Barbier, François', 'Lecuyer, Lucien', 'Lambert, Jérôme', 'Canet, Emmanuel']",Crit Care,,,True
65c5b049ad6a45d3533e0fee55018ba631d338b0,PMC,The enemy within: Targeting host–parasite interaction for antileishmanial drug discovery,http://dx.doi.org/10.1371/journal.pntd.0005480,PMC5464532,28594938,CC BY,"The state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites’ intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs. Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance. Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts. We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host–parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival.",2017 Jun 8,"['Lamotte, Suzanne', 'Späth, Gerald F.', 'Rachidi, Najma', 'Prina, Eric']",PLoS Negl Trop Dis,,,True
dda9765db3e9743ebe4387a47c51bf444118c5fe,PMC,The enemy within: Targeting host–parasite interaction for antileishmanial drug discovery,http://dx.doi.org/10.1371/journal.pntd.0005480,PMC5464532,28594938,CC BY,"The state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites’ intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs. Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance. Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts. We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host–parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival.",2017 Jun 8,"['Lamotte, Suzanne', 'Späth, Gerald F.', 'Rachidi, Najma', 'Prina, Eric']",PLoS Negl Trop Dis,,,False
551551b6447642735b59a49cbaa78a7b149b54d4,PMC,The enemy within: Targeting host–parasite interaction for antileishmanial drug discovery,http://dx.doi.org/10.1371/journal.pntd.0005480,PMC5464532,28594938,CC BY,"The state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites’ intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs. Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance. Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts. We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host–parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival.",2017 Jun 8,"['Lamotte, Suzanne', 'Späth, Gerald F.', 'Rachidi, Najma', 'Prina, Eric']",PLoS Negl Trop Dis,,,True
0b26d9ec6dfae866ae3f1a3f773036b1c8627147,PMC,Complete Genome of Avian coronavirus Vaccine Strains Ma5 and BR-I,http://dx.doi.org/10.1128/genomeA.00201-17,PMC5465604,28596385,CC BY,"Avian coronavirus (AvCoV) is a ubiquitous multiple-serotype pathogen of poultry, and its control is mainly based on the use of vaccines. We report here the previously unknown full genomes of the Ma5 (27,652 nucleotides [nt]) and BR-I (27,618 nt) AvCoV vaccine strains of the GI-1 (Massachusetts) and GI-11 (Brazil) types.",2017 Jun 8,"['Brandão, Paulo E.', 'Taniwaki, Sueli A.', 'Berg, Mikael', 'Hora, Aline S.']",Genome Announc,,,True
d08c4a6506c1a9b8fe7ace82d4c14f9636e1c33a,PMC,The cellular protein nucleolin preferentially binds long-looped G-quadruplex nucleic acids(),http://dx.doi.org/10.1016/j.bbagen.2016.11.036,PMC5466061,27913192,CC BY,"BACKGROUND: G-quadruplexes (G4s) are four-stranded nucleic acid structures that form in G-rich sequences. Nucleolin (NCL) is a cellular protein reported for its functions upon G4 recognition, such as induction of neurodegenerative diseases, tumor and virus mechanisms activation. We here aimed at defining NCL/G4 binding determinants. METHODS: Electrophoresis mobility shift assay was used to detect NCL/G4 binding; circular dichroism to assess G4 folding, topology and stability; dimethylsulfate footprinting to detect G bases involved in G4 folding. RESULTS: The purified full-length human NCL was initially tested on telomeric G4 target sequences to allow for modulation of loop, conformation, length, G-tract number, stability. G4s in promoter regions with more complex sequences were next employed. We found that NCL binding to G4s heavily relies on G4 loop length, independently of the conformation and oligonucleotide/loop sequence. Low stability G4s are preferred. When alternative G4 conformations are possible, those with longer loops are preferred upon binding to NCL, even if G-tracts need to be spared from G4 folding. CONCLUSIONS: Our data provide insight into how G4s and the associated proteins may control the ON/OFF molecular switch to several pathological processes, including neurodegeneration, tumor and virus activation. Understanding these regulatory determinants is the first step towards the development of targeted therapies. GENERAL SIGNIFICANCE: The indication that NCL binding preferentially stimulates and induces folding of G4s containing long loops suggests NCL ability to modify the overall structure and steric hindrance of the involved nucleic acid regions. This protein-induced modification of the G4 structure may represent a cellular mechanosensor mechanism to molecular signaling and disease pathogenesis. This article is part of a Special Issue entitled ""G-quadruplex"" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.",2017 May,"['Lago, Sara', 'Tosoni, Elena', 'Nadai, Matteo', 'Palumbo, Manlio', 'Richter, Sara N.']",Biochim Biophys Acta,,,False
0f7bb2b30b0eba1a065a6dfc88dbbd99053ff1ba,PMC,The cellular protein nucleolin preferentially binds long-looped G-quadruplex nucleic acids(),http://dx.doi.org/10.1016/j.bbagen.2016.11.036,PMC5466061,27913192,CC BY,"BACKGROUND: G-quadruplexes (G4s) are four-stranded nucleic acid structures that form in G-rich sequences. Nucleolin (NCL) is a cellular protein reported for its functions upon G4 recognition, such as induction of neurodegenerative diseases, tumor and virus mechanisms activation. We here aimed at defining NCL/G4 binding determinants. METHODS: Electrophoresis mobility shift assay was used to detect NCL/G4 binding; circular dichroism to assess G4 folding, topology and stability; dimethylsulfate footprinting to detect G bases involved in G4 folding. RESULTS: The purified full-length human NCL was initially tested on telomeric G4 target sequences to allow for modulation of loop, conformation, length, G-tract number, stability. G4s in promoter regions with more complex sequences were next employed. We found that NCL binding to G4s heavily relies on G4 loop length, independently of the conformation and oligonucleotide/loop sequence. Low stability G4s are preferred. When alternative G4 conformations are possible, those with longer loops are preferred upon binding to NCL, even if G-tracts need to be spared from G4 folding. CONCLUSIONS: Our data provide insight into how G4s and the associated proteins may control the ON/OFF molecular switch to several pathological processes, including neurodegeneration, tumor and virus activation. Understanding these regulatory determinants is the first step towards the development of targeted therapies. GENERAL SIGNIFICANCE: The indication that NCL binding preferentially stimulates and induces folding of G4s containing long loops suggests NCL ability to modify the overall structure and steric hindrance of the involved nucleic acid regions. This protein-induced modification of the G4 structure may represent a cellular mechanosensor mechanism to molecular signaling and disease pathogenesis. This article is part of a Special Issue entitled ""G-quadruplex"" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.",2017 May,"['Lago, Sara', 'Tosoni, Elena', 'Nadai, Matteo', 'Palumbo, Manlio', 'Richter, Sara N.']",Biochim Biophys Acta,,,False
de64592c6c3786b48b73cac2debc515c642e31f0,PMC,drVM: a new tool for efficient genome assembly of known eukaryotic viruses from metagenomes,http://dx.doi.org/10.1093/gigascience/gix003,PMC5466706,28369462,CC BY,"Background: Virus discovery using high-throughput next-generation sequencing has become more commonplace. However, although analysis of deep next-generation sequencing data allows us to identity potential pathogens, the entire analytical procedure requires competency in the bioinformatics domain, which includes implementing proper software packages and preparing prerequisite databases. Simple and user-friendly bioinformatics pipelines are urgently required to obtain complete viral genome sequences from metagenomic data. Results: This manuscript presents a pipeline, drVM (detect and reconstruct known viral genomes from metagenomes), for rapid viral read identification, genus-level read partition, read normalization, de novo assembly, sequence annotation, and coverage profiling. The first two procedures and sequence annotation rely on known viral genomes as a reference database. drVM was validated via the analysis of over 300 sequencing runs generated by Illumina and Ion Torrent platforms to provide complete viral genome assemblies for a variety of virus types including DNA viruses, RNA viruses, and retroviruses. drVM is available for free download at: https://sourceforge.net/projects/sb2nhri/files/drVM/ and is also assembled as a Docker container, an Amazon machine image, and a virtual machine to facilitate seamless deployment. Conclusions: drVM was compared with other viral detection tools to demonstrate its merits in terms of viral genome completeness and reduced computation time. This substantiates the platform's potential to produce prompt and accurate viral genome sequences from clinical samples.",2017 Jan 20,"['Lin, Hsin-Hung', 'Liao, Yu-Chieh']",Gigascience,,,True
83d150bdc1e4fdc24ecc74e0fd09d5fd7791cc65,PMC,Ficus septica plant extracts for treating Dengue virus in vitro,http://dx.doi.org/10.7717/peerj.3448,PMC5466810,28607841,CC BY,"Dengue virus types 1-4 (DENV-1-4) are positive-strand RNA viruses with an envelope that belongs to the Flaviviridae. DENV infection threatens human health worldwide. However, other than supportive treatments, no specific therapy is available for the infection. In order to discover novel medicine against DENV, we tested 59 crude extracts, without cytotoxicity, from 23 plants in vitro; immunofluorescence assay revealed that the methanol extracts of fruit, heartwood, leaves and stem from Ficus septica Burm. f. had a promising anti-DENV-1 and DENV-2 effect. However, infection with the non-envelope picornavirus, Aichi virus, was not inhibited by treatment with F. septica extracts. F. septica may be a candidate antiviral drug against an enveloped virus such as DENV.",2017 Jun 8,"['Huang, Nan-Chieh', 'Hung, Wan-Ting', 'Tsai, Wei-Lun', 'Lai, Feng-Yi', 'Lin, You-Sheng', 'Huang, Mei-Shu', 'Chen, Jih-Jung', 'Lin, Wei-Yu', 'Weng, Jing-Ru', 'Chang, Tsung-Hsien']",PeerJ,,,True
2b38999c47f55f18f27ce6dc678dc2b4df381043,PMC,DNA vaccination protects mice against Zika virus-induced damage to the testes,http://dx.doi.org/10.1038/ncomms15743,PMC5467228,28589934,CC BY,"Zika virus (ZIKV) is an emerging pathogen causally associated with serious sequelae in fetuses, inducing fetal microcephaly and other neurodevelopment defects. ZIKV is primarily transmitted by mosquitoes, but can persist in human semen and sperm, and sexual transmission has been documented. Moreover, exposure of type-I interferon knockout mice to ZIKV results in severe damage to the testes, epididymis and sperm. Candidate ZIKV vaccines have shown protective efficacy in preclinical studies carried out in animal models, and several vaccines have entered clinical trials. Here, we report that administration of a synthetic DNA vaccine encoding ZIKV pre-membrane and envelope (prME) completely protects mice against ZIKV-associated damage to the testes and sperm and prevents viral persistence in the testes following challenge with a contemporary strain of ZIKV. These data suggest that DNA vaccination merits further investigation as a potential means to reduce ZIKV persistence in the male reproductive tract.",2017 Jun 7,"['Griffin, Bryan D.', 'Muthumani, Kar', 'Warner, Bryce M.', 'Majer, Anna', 'Hagan, Mable', 'Audet, Jonathan', 'Stein, Derek R.', 'Ranadheera, Charlene', 'Racine, Trina', 'De La Vega, Marc-Antoine', 'Piret, Jocelyne', 'Kucas, Stephanie', 'Tran, Kaylie N.', 'Frost, Kathy L.', 'De Graff, Christine', 'Soule, Geoff', 'Scharikow, Leanne', 'Scott, Jennifer', 'McTavish, Gordon', 'Smid, Valerie', 'Park, Young K.', 'Maslow, Joel N.', 'Sardesai, Niranjan Y.', 'Kim, J. Joseph', 'Yao, Xiao-jian', 'Bello, Alexander', 'Lindsay, Robbin', 'Boivin, Guy', 'Booth, Stephanie A.', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'Safronetz, David', 'Weiner, David B.', 'Kobinger, Gary P.']",Nat Commun,,,True
da8495d556968a54927b3298f05cc5b574161897,PMC,DNA vaccination protects mice against Zika virus-induced damage to the testes,http://dx.doi.org/10.1038/ncomms15743,PMC5467228,28589934,CC BY,"Zika virus (ZIKV) is an emerging pathogen causally associated with serious sequelae in fetuses, inducing fetal microcephaly and other neurodevelopment defects. ZIKV is primarily transmitted by mosquitoes, but can persist in human semen and sperm, and sexual transmission has been documented. Moreover, exposure of type-I interferon knockout mice to ZIKV results in severe damage to the testes, epididymis and sperm. Candidate ZIKV vaccines have shown protective efficacy in preclinical studies carried out in animal models, and several vaccines have entered clinical trials. Here, we report that administration of a synthetic DNA vaccine encoding ZIKV pre-membrane and envelope (prME) completely protects mice against ZIKV-associated damage to the testes and sperm and prevents viral persistence in the testes following challenge with a contemporary strain of ZIKV. These data suggest that DNA vaccination merits further investigation as a potential means to reduce ZIKV persistence in the male reproductive tract.",2017 Jun 7,"['Griffin, Bryan D.', 'Muthumani, Kar', 'Warner, Bryce M.', 'Majer, Anna', 'Hagan, Mable', 'Audet, Jonathan', 'Stein, Derek R.', 'Ranadheera, Charlene', 'Racine, Trina', 'De La Vega, Marc-Antoine', 'Piret, Jocelyne', 'Kucas, Stephanie', 'Tran, Kaylie N.', 'Frost, Kathy L.', 'De Graff, Christine', 'Soule, Geoff', 'Scharikow, Leanne', 'Scott, Jennifer', 'McTavish, Gordon', 'Smid, Valerie', 'Park, Young K.', 'Maslow, Joel N.', 'Sardesai, Niranjan Y.', 'Kim, J. Joseph', 'Yao, Xiao-jian', 'Bello, Alexander', 'Lindsay, Robbin', 'Boivin, Guy', 'Booth, Stephanie A.', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'Safronetz, David', 'Weiner, David B.', 'Kobinger, Gary P.']",Nat Commun,,,False
02bb1c7a6ec483ce366cf2eb9b05d6da8906cd04,PMC,DNA vaccination protects mice against Zika virus-induced damage to the testes,http://dx.doi.org/10.1038/ncomms15743,PMC5467228,28589934,CC BY,"Zika virus (ZIKV) is an emerging pathogen causally associated with serious sequelae in fetuses, inducing fetal microcephaly and other neurodevelopment defects. ZIKV is primarily transmitted by mosquitoes, but can persist in human semen and sperm, and sexual transmission has been documented. Moreover, exposure of type-I interferon knockout mice to ZIKV results in severe damage to the testes, epididymis and sperm. Candidate ZIKV vaccines have shown protective efficacy in preclinical studies carried out in animal models, and several vaccines have entered clinical trials. Here, we report that administration of a synthetic DNA vaccine encoding ZIKV pre-membrane and envelope (prME) completely protects mice against ZIKV-associated damage to the testes and sperm and prevents viral persistence in the testes following challenge with a contemporary strain of ZIKV. These data suggest that DNA vaccination merits further investigation as a potential means to reduce ZIKV persistence in the male reproductive tract.",2017 Jun 7,"['Griffin, Bryan D.', 'Muthumani, Kar', 'Warner, Bryce M.', 'Majer, Anna', 'Hagan, Mable', 'Audet, Jonathan', 'Stein, Derek R.', 'Ranadheera, Charlene', 'Racine, Trina', 'De La Vega, Marc-Antoine', 'Piret, Jocelyne', 'Kucas, Stephanie', 'Tran, Kaylie N.', 'Frost, Kathy L.', 'De Graff, Christine', 'Soule, Geoff', 'Scharikow, Leanne', 'Scott, Jennifer', 'McTavish, Gordon', 'Smid, Valerie', 'Park, Young K.', 'Maslow, Joel N.', 'Sardesai, Niranjan Y.', 'Kim, J. Joseph', 'Yao, Xiao-jian', 'Bello, Alexander', 'Lindsay, Robbin', 'Boivin, Guy', 'Booth, Stephanie A.', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'Safronetz, David', 'Weiner, David B.', 'Kobinger, Gary P.']",Nat Commun,,,False
72c358060f8600b70abafbe9faa93aed79d87ada,PMC,"One Health, emerging infectious diseases and wildlife: two decades of progress?",http://dx.doi.org/10.1098/rstb.2016.0167,PMC5468692,28584175,CC BY,"Infectious diseases affect people, domestic animals and wildlife alike, with many pathogens being able to infect multiple species. Fifty years ago, following the wide-scale manufacture and use of antibiotics and vaccines, it seemed that the battle against infections was being won for the human population. Since then, however, and in addition to increasing antimicrobial resistance among bacterial pathogens, there has been an increase in the emergence of, mostly viral, zoonotic diseases from wildlife, sometimes causing fatal outbreaks of epidemic proportions. Concurrently, infectious disease has been identified as an increasing threat to wildlife conservation. A synthesis published in 2000 showed common anthropogenic drivers of disease threats to biodiversity and human health, including encroachment and destruction of wildlife habitat and the human-assisted spread of pathogens. Almost two decades later, the situation has not changed and, despite improved knowledge of the underlying causes, little has been done at the policy level to address these threats. For the sake of public health and wellbeing, human-kind needs to work better to conserve nature and preserve the ecosystem services, including disease regulation, that biodiversity provides while also understanding and mitigating activities which lead to disease emergence. We consider that holistic, One Health approaches to the management and mitigation of the risks of emerging infectious diseases have the greatest chance of success. This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’.",2017 Jul 19,"['Cunningham, Andrew A.', 'Daszak, Peter', 'Wood, James L. N.']",Philos Trans R Soc Lond B Biol Sci,,,True
f6453a0485975f0892250dc5821c218633339584,PMC,One Health contributions towards more effective and equitable approaches to health in low- and middle-income countries,http://dx.doi.org/10.1098/rstb.2016.0168,PMC5468693,28584176,CC BY,"Emerging zoonoses with pandemic potential are a stated priority for the global health security agenda, but endemic zoonoses also have a major societal impact in low-resource settings. Although many endemic zoonoses can be treated, timely diagnosis and appropriate clinical management of human cases is often challenging. Preventive ‘One Health’ interventions, e.g. interventions in animal populations that generate human health benefits, may provide a useful approach to overcoming some of these challenges. Effective strategies, such as animal vaccination, already exist for the prevention, control and elimination of many endemic zoonoses, including rabies, and several livestock zoonoses (e.g. brucellosis, leptospirosis, Q fever) that are important causes of human febrile illness and livestock productivity losses in low- and middle-income countries. We make the case that, for these diseases, One Health interventions have the potential to be more effective and generate more equitable benefits for human health and livelihoods, particularly in rural areas, than approaches that rely exclusively on treatment of human cases. We hypothesize that applying One Health interventions to tackle these health challenges will help to build trust, community engagement and cross-sectoral collaboration, which will in turn strengthen the capacity of fragile health systems to respond to the threat of emerging zoonoses and other future health challenges. One Health interventions thus have the potential to align the ongoing needs of disadvantaged communities with the concerns of the broader global community, providing a pragmatic and equitable approach to meeting the global goals for sustainable development and supporting the global health security agenda. This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’.",2017 Jul 19,"['Cleaveland, S.', 'Sharp, J.', 'Abela-Ridder, B.', 'Allan, K. J.', 'Buza, J.', 'Crump, J. A.', 'Davis, A.', 'Del Rio Vilas, V. J.', 'de Glanville, W. A.', 'Kazwala, R. R.', 'Kibona, T.', 'Lankester, F. J.', 'Lugelo, A.', 'Mmbaga, B. T.', 'Rubach, M. P.', 'Swai, E. S.', 'Waldman, L.', 'Haydon, D. T.', 'Hampson, K.', 'Halliday, J. E. B.']",Philos Trans R Soc Lond B Biol Sci,,,True
f06f323520d1a5233daf8ef62adb0df997675401,PMC,"Zoonoses, One Health and complexity: wicked problems and constructive conflict",http://dx.doi.org/10.1098/rstb.2016.0171,PMC5468696,28584179,CC BY,"Infectious zoonoses emerge from complex interactions among social and ecological systems. Understanding this complexity requires the accommodation of multiple, often conflicting, perspectives and narratives, rooted in different value systems and temporal–spatial scales. Therefore, to be adaptive, successful and sustainable, One Health approaches necessarily entail conflicts among observers, practitioners and scholars. Nevertheless, these integrative approaches have, both implicitly and explicitly, tended to marginalize some perspectives and prioritize others, resulting in a kind of technocratic tyranny. An important function of One Health approaches should be to facilitate and manage those conflicts, rather than to impose solutions. This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’.",2017 Jul 19,"Waltner-Toews, David",Philos Trans R Soc Lond B Biol Sci,,,True
adbb693cc7e5436489cb3043cecc6f28a346c7ed,PMC,Facility-based surveillance for emerging infectious diseases; diagnostic practices in rural West African hospital settings: observations from Ghana,http://dx.doi.org/10.1098/rstb.2016.0544,PMC5468698,28584181,CC BY,"The aim of this study was to better understand the effectiveness of Integrated Disease Surveillance and Response (IDSR) facility-based surveillance in detecting newly emerging infectious diseases (EIDs) in rural West African settings. A six-month ethnographic study was undertaken in 2012 in the Techiman Municipality of the Brong-Ahafo Region of Ghana, aimed at documenting the trajectories of febrile illness cases of unknown origin occurring within four rural communities. Particular attention was paid to where these trajectories involved the use of formal healthcare facilities and the diagnostic practices that occurred there. Seventy-six participants were enrolled in the study, and 24 complete episodes of illness were documented. While participants routinely used hospital treatment when confronted with enduring or severe illness, the diagnostic process within clinical settings meant that an unusual diagnosis, such as an EID, was unlikely to be considered. Facility-based surveillance is unlikely to be effective in detecting EIDs due to a combination of clinical care practices and the time constraints associated with individual episodes of illness, particularly in the resource-limited settings of rural West Africa, where febrile illness due to malaria is common and specific diagnostic assays are largely unavailable. The success of the ‘One Health' approach to EIDs in West Africa is predicated on characterization of accurately diagnosed disease burdens. To this end, we must address inefficiencies in the dominant approaches to EID surveillance and the weaknesses of health systems in the region generally. This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being'.",2017 Jul 19,"['Jephcott, Freya L.', 'Wood, James L. N.', 'Cunningham, Andrew A.']",Philos Trans R Soc Lond B Biol Sci,,,True
a9cab864aceb9a873c6a049a8d7951ac80d993d8,PMC,A reverse genetics system for avian coronavirus infectious bronchitis virus based on targeted RNA recombination,http://dx.doi.org/10.1186/s12985-017-0775-8,PMC5468965,28606144,CC BY,"BACKGROUND: Avian coronavirus infectious bronchitis virus (IBV) is a respiratory pathogen of chickens that causes severe economic losses in the poultry industry worldwide. Major advances in the study of the molecular biology of IBV have resulted from the development of reverse genetics systems for the highly attenuated, cell culture-adapted, IBV strain Beaudette. However, most IBV strains, amongst them virulent field isolates, can only be propagated in embryonated chicken eggs, and not in continuous cell lines. METHODS: We established a reverse genetics system for the IBV strain H52, based on targeted RNA recombination in a two-step process. First, a genomic and a chimeric synthetic, modified IBV RNA were co-transfected into non-susceptible cells to generate a recombinant chimeric murinized (m) IBV intermediate (mIBV). Herein, the genomic part coding for the spike glycoprotein ectodomain was replaced by that of the coronavirus mouse hepatitis virus (MHV), allowing for the selection and propagation of recombinant mIBV in murine cells. In the second step, mIBV was used as the recipient. To this end a recombination with synthetic RNA comprising the 3′-end of the IBV genome was performed by introducing the complete IBV spike gene, allowing for the rescue and selection of candidate recombinants in embryonated chicken eggs. RESULTS: Targeted RNA recombination allowed for the modification of the 3′-end of the IBV genome, encoding all structural and accessory genes. A wild-type recombinant IBV was constructed, containing several synonymous marker mutations. The in ovo growth kinetics and in vivo characteristics of the recombinant virus were similar to those of the parental IBV strain H52. CONCLUSIONS: Targeted RNA recombination allows for the generation of recombinant IBV strains that are not able to infect and propagate in continuous cell lines. The ability to introduce specific mutations holds promise for the development of rationally designed live-attenuated IBV vaccines and for studies into the biology of IBV in general. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-017-0775-8) contains supplementary material, which is available to authorized users.",2017 Jun 12,"['van Beurden, Steven J.', 'Berends, Alinda J.', 'Krämer-Kühl, Annika', 'Spekreijse, Dieuwertje', 'Chénard, Gilles', 'Philipp, Hans-Christian', 'Mundt, Egbert', 'Rottier, Peter J. M.', 'Verheije, M. Hélène']",Virol J,,,True
603e11d248463c9b79a1030663946c5640810536,PMC,Bacillus subtilis and surfactin inhibit the transmissible gastroenteritis virus from entering the intestinal epithelial cells,http://dx.doi.org/10.1042/BSR20170082,PMC5469330,28270576,CC BY,"Intestinal epithelial cells are the targets for transmissible gastroenteritis (TGE) virus (TGEV) infection. It is urgent to develop a novel candidate against TGEV entry. Bacillus subtilis is a probiotic with excellent anti-microorganism properties and one of its secretions, surfactin, has been regarded as a versatile weapon for most plant pathogens, especially for the enveloped virus. We demonstrate for the first time that B. subtilis OKB105 and its surfactin can effectively inhibit one animal coronavirus, TGEV, entering the intestinal porcine epithelial cell line (IPEC-J2). Then, several different experiments were performed to seek the might mechanisms. The plaque assays showed that surfactant could reduce the plaque generation of TGEV in a dose-dependent manner. Meanwhile, after incubation with TGEV for 1.5 h, B. subtilis could attach TGEV particles to their surface so that the number of virus to bind to the host cells was declined. Furthermore, our data showed that the inhibition of B. subtilis was closely related to the competition with TGEV for the viral entry receptors, including epidermal growth factor receptor (EGFR) and aminopeptidase N (APN) protein. In addition, Western blotting and apoptosis analysis indicated that B. subtilis could enhance the resistance of IPEC-J2 cells by up-regulating the expression of toll-like receptor (TLR)-6 and reducing the percentage of apoptotic cells. Taken together, our results suggest that B. subtilis OKB105 and its surfactin can antagonize TGEV entry in vitro and may serve as promising new candidates for TGEV prevention.",2017 Apr 10,"['Wang, Xiaoqing', 'Hu, Weiwei', 'Zhu, Liqi', 'Yang, Qian']",Biosci Rep,,,True
39ad6d2aa80498b55d03ac9d7f5a4adaaaaf574b,PMC,Functional and Homeostatic Impact of Age-Related Changes in Lymph Node Stroma,http://dx.doi.org/10.3389/fimmu.2017.00706,PMC5469916,28659930,CC BY,"Adults over 65 years of age are more vulnerable to infectious disease and show poor responses to vaccination relative to those under 50. A complex set of age-related changes in the immune system is believed to be largely responsible for these defects. These changes, collectively termed immune senescence, encompass alterations in both the innate and adaptive immune systems, in the microenvironments where immune cells develop or reside, and in soluble factors that guide immune homeostasis and function. While age-related changes in primary lymphoid organs (bone marrow, and, in particular, the thymus, which involutes in the first third of life) have been long appreciated, changes affecting aging secondary lymphoid organs, and, in particular, aging lymph nodes (LNs) have been less well characterized. Over the last 20 years, LN stromal cells have emerged as key players in maintaining LN morphology and immune homeostasis, as well as in coordinating immune responses to pathogens. Here, we review recent progress in understanding the contributions of LN stromal cells to immune senescence. We discuss approaches to understand the mechanisms behind the decline in LN stromal cells and conclude by considering potential strategies to rejuvenate aging LN stroma to improve immune homeostasis, immune responses, and vaccine efficacy in the elderly.",2017 Jun 14,"['Thompson, Heather L.', 'Smithey, Megan J.', 'Surh, Charles D.', 'Nikolich-Žugich, Janko']",Front Immunol,,,True
38df3b1f635f3643d1a818ea62ac60915d71e92c,PMC,Stimulating collaboration between human and veterinary health care professionals,http://dx.doi.org/10.1186/s12917-017-1072-x,PMC5470326,28610617,CC BY,"BACKGROUND: Despite the need to control outbreaks of (emerging) zoonotic diseases and the need for added value in comparative/translational medicine, jointly addressed in the One Health approach [One health Initiative (n.d.a). About the One Health Initiative. http://www.onehealthinitiative.com/about.php. Accessed 13 September 2016], collaboration between human and veterinary health care professionals is limited. This study focuses on the social dilemma experienced by health care professionals and ways in which an interdisciplinary approach could be developed. RESULTS: Based on Gaertner and Dovidio’s Common Ingroup Identity Model, a number of questionnaires were designed and tested; with PROGRESS, the relation between collaboration and common goal was assessed, mediated by decategorization, recategorization, mutual differentiation and knowledge sharing. This study confirms the Common Ingroup Identity Model stating that common goals stimulate collaboration. Decategorization and mutual differentiation proved to be significant in this relationship; recategorization and knowledge sharing mediate this relation. CONCLUSIONS: It can be concluded that the Common Ingroup Identity Model theory helps us to understand how health care professionals perceive the One Health initiative and how they can intervene in this process. In the One Health approach, professional associations could adopt a facilitating role.",2017 Jun 13,"['Eussen, Björn G.M.', 'Schaveling, Jaap', 'Dragt, Maria J.', 'Blomme, Robert Jan']",BMC Vet Res,,,True
07bf7b392feb438d436be66e2bdfe7513320231b,PMC,"Estimation of basic reproduction number of the Middle East respiratory syndrome coronavirus (MERS-CoV) during the outbreak in South Korea, 2015",http://dx.doi.org/10.1186/s12938-017-0370-7,PMC5470331,28610609,CC BY,"BACKGROUND: In South Korea, an outbreak of Middle East respiratory syndrome (MERS) occurred in 2015. It was the second largest MERS outbreak. As a result of the outbreak in South Korea, 186 infections were reported, and 36 patients died. At least 16,693 people were isolated with suspicious symptoms. This paper estimates the basic reproduction number of the MERS coronavirus (CoV), using data on the spread of MERS in South Korea. METHODS: The basic reproduction number of an epidemic is defined as the average number of secondary cases that an infected subject produces over its infectious period in a susceptible and uninfected population. To estimate the basic reproduction number of the MERS-CoV, we employ data from the 2015 South Korea MERS outbreak and the susceptible-infected-removed (SIR) model, a mathematical model that uses a set of ordinary differential equations (ODEs). RESULTS: We fit the model to the epidemic data of the South Korea outbreak minimizing the sum of the squared errors to identify model parameters. Also we derive the basic reproductive number as the terms of the parameters of the SIR model. Then we determine the basic reproduction number of the MERS-CoV in South Korea in 2015 as 8.0977. It is worth comparing with the basic reproductive number of the 2014 Ebola outbreak in West Africa including Guinea, Sierra Leone, and Liberia, which had values of 1.5–2.5. CONCLUSIONS: There was no intervention to control the infection in the early phase of the outbreak, thus the data used here provide the best conditions to evaluate the epidemic characteristics of MERS, such as the basic reproduction number. An evaluation of basic reproduction number using epidemic data could be problematic if there are stochastic fluctuations in the early phase of the outbreak, or if the report is not accurate and there is bias in the data. Such problems are not relevant to this study because the data used here were precisely reported and verified by Korea Hospital Association.",2017 Jun 13,"Chang, Hyuk-Jun",Biomed Eng Online,,,True
d9664a611b4984ab4c6a6000a55ae8b495f7e997,PMC,Encouraging rational antibiotic use in childhood pneumonia: a focus on Vietnam and the Western Pacific Region,http://dx.doi.org/10.1186/s41479-017-0031-4,PMC5471677,28702309,CC BY,"Globally, pneumonia is considered to be the biggest killer of infants and young children (aged <5 years) outside the neonatal period, with the greatest disease burden in low- and middle-income countries. Optimal management of childhood pneumonia is challenging in settings where clinicians have limited information regarding the local pathogen and drug resistance profiles. This frequently results in unnecessary and poorly targeted antibiotic use. Restricting antibiotic use is a global priority, particularly in Asia and the Western Pacific Region where excessive use is driving high rates of antimicrobial resistance. The authors conducted a comprehensive literature review to explore the antibiotic resistance profile of bacteria associated with pneumonia in the Western Pacific Region, with a focus on Vietnam. Current management practices were also considered, along with the diagnostic dilemmas faced by doctors and other factors that increase unnecessary antibiotic use. This review offers some suggestions on how these issues may be addressed.",2017 Apr 25,"['Phuong, Nguyen T. K.', 'Hoang, Tran T.', 'Van, Pham H.', 'Tu, Lolyta', 'Graham, Stephen M.', 'Marais, Ben J.']",Pneumonia (Nathan),,,True
a257c576fef2e2aee2702b5179d2d09473f16543,PMC,Pulmonary infections in the returned traveller,http://dx.doi.org/10.1186/s41479-017-0026-1,PMC5471882,28702303,CC BY,"Pulmonary infections in the returned traveller are a common presentation. A wide variety of infections may present with pulmonary symptoms. It is important for clinicians to differentiate the cause of these symptoms. The risk of contracting certain travel-related pulmonary diseases depends on travel destination, length of stay, activities undertaken and co-morbidities. Some pathogens are found worldwide, whilst others are related to specific locations. This review article will discuss the approach to diagnosing and treating pulmonary infections in the returned traveller.",2017 Jan 25,"['Trimble, Ashleigh', 'Moffat, V.', 'Collins, A. M.']",Pneumonia (Nathan),,,True
f061e6719f37322dba23bdecaaa47e68fb2c04b4,PMC,Impact of viral multiplex real-time PCR on management of respiratory tract infection: a retrospective cohort study,http://dx.doi.org/10.1186/s41479-017-0028-z,PMC5471894,28702306,CC BY,"BACKGROUND: Significance and clinical utility of multiple virus detection by multiplex real-time polymerase chain reaction (rtPCR) in respiratory tract infection remain unclear. METHODS: This retrospective cohort study analyzed how virus detection affected clinical management. During a 27-month period, clinical and laboratory information was collected from all children and adults in two Swiss tertiary centres whose respiratory samples were tested for respiratory viruses with a 16-plex rtPCR test. RESULTS: Pathogens were identified in 140 of 254 patients (55%); of those patients, there was ≥1 virus in 91 (65%), ≥ 1 bacterium in 53 (38%), and ≥1 virus and bacterium in 11 (8%). Of 80 patients with viral infection, 59 (74%) received antibiotics. Virus detection was associated with discontinuation of antibiotics in 2 of 20 adults (10%) and 6 of 14 children (43%). Overall 12 adults (34%) and 18 children (67%) were managed correctly without antibiotics after virus detection (p = 0.01). When taking biomarkers, radiologic presentations, and antibiotic pre-treatment into account, the impact of rtPCR and appropriateness of therapy for clinically viral infections increased to 100% in children and 62% in adults. CONCLUSIONS: A substantial reduction of unnecessary antibiotic prescriptions seems possible. Appropriate application of rtPCR results in respiratory tract infections should be encouraged.",2017 Feb 25,"['Mayer, Lena M.', 'Kahlert, Christian', 'Rassouli, Frank', 'Vernazza, Pietro', 'Albrich, Werner C.']",Pneumonia (Nathan),,,True
fda6cb46a1b95c00e07ca21e9e9e63b66bbaf150,PMC,Biodistribution and residence time of adenovector serotype 5 in normal and immunodeficient mice and rats detected with bioluminescent imaging,http://dx.doi.org/10.1038/s41598-017-03852-0,PMC5472566,28620164,CC BY,"As concerns increase about adenovirus type 5 (Ad5) being a safe gene transfer vector, it is important to evaluate its distribution, residence time, and possible toxicity in immunodeficient populations. To characterize the potential risk associated with different Ad5 vector delivery modes, we used immunocompetent and immunodeficient Rag2 (−/−) animals to establish mouse and rat models that could be monitored with bioluminescent imaging following intramuscular or intravascular infection with an engineered replication-incompetent Ad5 virus carrying the firefly luciferase gene (Ad5-Fluc). The Ad5 vector was less well-tolerated by Rag2 (−/−) animals than by wildtype ones, with delayed residence time, wider virus dissemination, less weight gain, and relatively severe pathological changes. In intravascularly Ad5-Fluc-infected Rag2 (−/−) mice, systemic virus dissemination extended from the abdomen to the limbs and head on day 9 post-infection. Additionally, significant increases in plasma TNF-α and IFN-γ, which may be important factors in the heightened immunopathology in the liver and brain, were detected in the Rag2 (−/−) mice 30 days after intravascular delivery. The Ad5 vector was better tolerated after intramuscular delivery than after intravascular delivery. Ad5-Fluc/Rag2 (−/−) mice and rats can be used as reliable models of an immunodeficient population in which to evaluate the safety of Ad5-vectored vaccines or gene therapy products.",2017 Jun 15,"['Liu, Qiang', 'Zhou, Shuya', 'Fan, Changfa', 'Huang, Weijin', 'Li, Qianqian', 'Liu, Susu', 'Wu, Xi', 'Li, Baowen', 'Wang, Youchun']",Sci Rep,,,False
a30cef8b3428aa804aa2cbf0ec0303827bb09514,PMC,Biodistribution and residence time of adenovector serotype 5 in normal and immunodeficient mice and rats detected with bioluminescent imaging,http://dx.doi.org/10.1038/s41598-017-03852-0,PMC5472566,28620164,CC BY,"As concerns increase about adenovirus type 5 (Ad5) being a safe gene transfer vector, it is important to evaluate its distribution, residence time, and possible toxicity in immunodeficient populations. To characterize the potential risk associated with different Ad5 vector delivery modes, we used immunocompetent and immunodeficient Rag2 (−/−) animals to establish mouse and rat models that could be monitored with bioluminescent imaging following intramuscular or intravascular infection with an engineered replication-incompetent Ad5 virus carrying the firefly luciferase gene (Ad5-Fluc). The Ad5 vector was less well-tolerated by Rag2 (−/−) animals than by wildtype ones, with delayed residence time, wider virus dissemination, less weight gain, and relatively severe pathological changes. In intravascularly Ad5-Fluc-infected Rag2 (−/−) mice, systemic virus dissemination extended from the abdomen to the limbs and head on day 9 post-infection. Additionally, significant increases in plasma TNF-α and IFN-γ, which may be important factors in the heightened immunopathology in the liver and brain, were detected in the Rag2 (−/−) mice 30 days after intravascular delivery. The Ad5 vector was better tolerated after intramuscular delivery than after intravascular delivery. Ad5-Fluc/Rag2 (−/−) mice and rats can be used as reliable models of an immunodeficient population in which to evaluate the safety of Ad5-vectored vaccines or gene therapy products.",2017 Jun 15,"['Liu, Qiang', 'Zhou, Shuya', 'Fan, Changfa', 'Huang, Weijin', 'Li, Qianqian', 'Liu, Susu', 'Wu, Xi', 'Li, Baowen', 'Wang, Youchun']",Sci Rep,,,True
aa6296fbdf1112783dddb75887910f98791bdd0e,PMC,An anti vimentin antibody promotes tube formation,http://dx.doi.org/10.1038/s41598-017-03799-2,PMC5472577,28620205,CC BY,"In recent years, there has been an increasing appreciation of the importance of secreted and extracellular proteins that traditionally have been considered as intracellular components. Vimentin is a highly abundant intermediate filament protein, and its intracellular functions have been investigated in a large number of studies. Recently, however, vimentin has been shown to take part in significant processes outside the cell. Our understanding of the functions of extracellular vimentin is, however, limited. In this study we demonstrate that a vimentin specific antibody, obtained by phage antibody technology, promotes tube formation of endothelial cells in a 2D matrigel assay. By binding vimentin, the antibody increases the tube formation by 21% after 5 hours of incubation. Addition of the antibody directly to cultured endothelial cells does not influence endothelial cell migration or proliferation. The enhanced tube formation can be seen for up to 10 hours where after the effect decreases. It is shown that the antibody-binding site is located on the coil 2 domain of vimentin. To our knowledge this is the first study that demonstrates an enhanced tube formation by binding vimentin in a 2D matrigel assay under normoxic conditions.",2017 Jun 15,"['Jørgensen, Mathias Lindh', 'Møller, Carina Kjeldahl', 'Rasmussen, Lasse', 'Boisen, Louise', 'Pedersen, Henrik', 'Kristensen, Peter']",Sci Rep,,,False
24d4ea00f8f0e950b98a668d62f780396d3cad68,PMC,An anti vimentin antibody promotes tube formation,http://dx.doi.org/10.1038/s41598-017-03799-2,PMC5472577,28620205,CC BY,"In recent years, there has been an increasing appreciation of the importance of secreted and extracellular proteins that traditionally have been considered as intracellular components. Vimentin is a highly abundant intermediate filament protein, and its intracellular functions have been investigated in a large number of studies. Recently, however, vimentin has been shown to take part in significant processes outside the cell. Our understanding of the functions of extracellular vimentin is, however, limited. In this study we demonstrate that a vimentin specific antibody, obtained by phage antibody technology, promotes tube formation of endothelial cells in a 2D matrigel assay. By binding vimentin, the antibody increases the tube formation by 21% after 5 hours of incubation. Addition of the antibody directly to cultured endothelial cells does not influence endothelial cell migration or proliferation. The enhanced tube formation can be seen for up to 10 hours where after the effect decreases. It is shown that the antibody-binding site is located on the coil 2 domain of vimentin. To our knowledge this is the first study that demonstrates an enhanced tube formation by binding vimentin in a 2D matrigel assay under normoxic conditions.",2017 Jun 15,"['Jørgensen, Mathias Lindh', 'Møller, Carina Kjeldahl', 'Rasmussen, Lasse', 'Boisen, Louise', 'Pedersen, Henrik', 'Kristensen, Peter']",Sci Rep,,,True
f2775e93528da5c439a57c542b520d873c8d3e4e,PMC,The Intestinal Eukaryotic and Bacterial Biome of Spotted Hyenas: The Impact of Social Status and Age on Diversity and Composition,http://dx.doi.org/10.3389/fcimb.2017.00262,PMC5472691,28670573,CC BY,"In mammals, two factors likely to affect the diversity and composition of intestinal bacteria (bacterial microbiome) and eukaryotes (eukaryome) are social status and age. In species in which social status determines access to resources, socially dominant animals maintain better immune processes and health status than subordinates. As high species diversity is an index of ecosystem health, the intestinal biome of healthier, socially dominant animals should be more diverse than those of subordinates. Gradual colonization of the juvenile intestine after birth predicts lower intestinal biome diversity in juveniles than adults. We tested these predictions on the effect of: (1) age (juvenile/adult) and (2) social status (low/high) on bacterial microbiome and eukaryome diversity and composition in the spotted hyena (Crocuta crocuta), a highly social, female-dominated carnivore in which social status determines access to resources. We comprehensively screened feces from 35 individually known adult females and 7 juveniles in the Serengeti ecosystem for bacteria and eukaryotes, using a set of 48 different amplicons (4 for bacterial 16S, 44 for eukaryote 18S) in a multi-amplicon sequencing approach. We compared sequence abundances to classical coprological egg or oocyst counts. For all parasite taxa detected in more than six samples, the number of sequence reads significantly predicted the number of eggs or oocysts counted, underscoring the value of an amplicon sequencing approach for quantitative measurements of parasite load. In line with our predictions, our results revealed a significantly less diverse microbiome in juveniles than adults and a significantly higher diversity of eukaryotes in high-ranking than low-ranking animals. We propose that free-ranging wildlife can provide an intriguing model system to assess the adaptive value of intestinal biome diversity for both bacteria and eukaryotes.",2017 Jun 16,"['Heitlinger, Emanuel', 'Ferreira, Susana C. M.', 'Thierer, Dagmar', 'Hofer, Heribert', 'East, Marion L.']",Front Cell Infect Microbiol,,,True
130c4c6c7faab2f0c0143b6f0cd0118b27c91dea,PMC,Complement Evasion Strategies of Viruses: An Overview,http://dx.doi.org/10.3389/fmicb.2017.01117,PMC5472698,28670306,CC BY,"Being a major first line of immune defense, the complement system keeps a constant vigil against viruses. Its ability to recognize large panoply of viruses and virus-infected cells, and trigger the effector pathways, results in neutralization of viruses and killing of the infected cells. This selection pressure exerted by complement on viruses has made them evolve a multitude of countermeasures. These include targeting the recognition molecules for the avoidance of detection, targeting key enzymes and complexes of the complement pathways like C3 convertases and C5b-9 formation – either by encoding complement regulators or by recruiting membrane-bound and soluble host complement regulators, cleaving complement proteins by encoding protease, and inhibiting the synthesis of complement proteins. Additionally, viruses also exploit the complement system for their own benefit. For example, they use complement receptors as well as membrane regulators for cellular entry as well as their spread. Here, we provide an overview on the complement subversion mechanisms adopted by the members of various viral families including Poxviridae, Herpesviridae, Adenoviridae, Flaviviridae, Retroviridae, Picornaviridae, Astroviridae, Togaviridae, Orthomyxoviridae and Paramyxoviridae.",2017 Jun 16,"['Agrawal, Palak', 'Nawadkar, Renuka', 'Ojha, Hina', 'Kumar, Jitendra', 'Sahu, Arvind']",Front Microbiol,,,True
62918573a167d69a0056aa9462d5cc1d9ae351fa,PMC,Protein-directed ribosomal frameshifting temporally regulates gene expression,http://dx.doi.org/10.1038/ncomms15582,PMC5472766,28593994,CC BY,"Programmed −1 ribosomal frameshifting is a mechanism of gene expression, whereby specific signals within messenger RNAs direct a proportion of translating ribosomes to shift −1 nt and continue translating in the new reading frame. Such frameshifting normally occurs at a set ratio and is utilized in the expression of many viral genes and a number of cellular genes. An open question is whether proteins might function as trans-acting switches to turn frameshifting on or off in response to cellular conditions. Here we show that frameshifting in a model RNA virus, encephalomyocarditis virus, is trans-activated by viral protein 2A. As a result, the frameshifting efficiency increases from 0 to 70% (one of the highest known in a mammalian system) over the course of infection, temporally regulating the expression levels of the viral structural and enzymatic proteins.",2017 Jun 8,"['Napthine, Sawsan', 'Ling, Roger', 'Finch, Leanne K.', 'Jones, Joshua D.', 'Bell, Susanne', 'Brierley, Ian', 'Firth, Andrew E.']",Nat Commun,,,True
6079a624f38ef12deaa21ba629437cdaf24ef8d4,PMC,Protein-directed ribosomal frameshifting temporally regulates gene expression,http://dx.doi.org/10.1038/ncomms15582,PMC5472766,28593994,CC BY,"Programmed −1 ribosomal frameshifting is a mechanism of gene expression, whereby specific signals within messenger RNAs direct a proportion of translating ribosomes to shift −1 nt and continue translating in the new reading frame. Such frameshifting normally occurs at a set ratio and is utilized in the expression of many viral genes and a number of cellular genes. An open question is whether proteins might function as trans-acting switches to turn frameshifting on or off in response to cellular conditions. Here we show that frameshifting in a model RNA virus, encephalomyocarditis virus, is trans-activated by viral protein 2A. As a result, the frameshifting efficiency increases from 0 to 70% (one of the highest known in a mammalian system) over the course of infection, temporally regulating the expression levels of the viral structural and enzymatic proteins.",2017 Jun 8,"['Napthine, Sawsan', 'Ling, Roger', 'Finch, Leanne K.', 'Jones, Joshua D.', 'Bell, Susanne', 'Brierley, Ian', 'Firth, Andrew E.']",Nat Commun,,,False
bfb2b592ab48cabbcf176b7954b5f55dcd5d5e3d,PMC,Protein-directed ribosomal frameshifting temporally regulates gene expression,http://dx.doi.org/10.1038/ncomms15582,PMC5472766,28593994,CC BY,"Programmed −1 ribosomal frameshifting is a mechanism of gene expression, whereby specific signals within messenger RNAs direct a proportion of translating ribosomes to shift −1 nt and continue translating in the new reading frame. Such frameshifting normally occurs at a set ratio and is utilized in the expression of many viral genes and a number of cellular genes. An open question is whether proteins might function as trans-acting switches to turn frameshifting on or off in response to cellular conditions. Here we show that frameshifting in a model RNA virus, encephalomyocarditis virus, is trans-activated by viral protein 2A. As a result, the frameshifting efficiency increases from 0 to 70% (one of the highest known in a mammalian system) over the course of infection, temporally regulating the expression levels of the viral structural and enzymatic proteins.",2017 Jun 8,"['Napthine, Sawsan', 'Ling, Roger', 'Finch, Leanne K.', 'Jones, Joshua D.', 'Bell, Susanne', 'Brierley, Ian', 'Firth, Andrew E.']",Nat Commun,,,False
13a1c758877b216e51c51e9ee532ab5c3e0c12fb,PMC,Pulmonary diseases induced by ambient ultrafine and engineered nanoparticles in twenty-first century,http://dx.doi.org/10.1093/nsr/nww064,PMC5473351,28649460,CC BY,"Air pollution is a severe threat to public health globally, affecting everyone in developed and developing countries alike. Among different air pollutants, particulate matter (PM), particularly combustion-produced fine PM (PM(2.5)) has been shown to play a major role in inducing various adverse health effects. Strong associations have been demonstrated by epidemiological and toxicological studies between increases in PM(2.5) concentrations and premature mortality, cardiopulmonary diseases, asthma and allergic sensitization, and lung cancer. The mechanisms of PM-induced toxicological effects are related to their size, chemical composition, lung clearance and retention, cellular oxidative stress responses and pro-inflammatory effects locally and systemically. Particles in the ultrafine range (<100 nm), although they have the highest number counts, surface area and organic chemical content, are often overlooked due to insufficient monitoring and risk assessment. Yet, ample studies have demonstrated that ambient ultrafine particles have higher toxic potential compared with PM(2.5). In addition, the rapid development of nanotechnology, bringing ever-increasing production of nanomaterials, has raised concerns about the potential human exposure and health impacts. All these add to the complexity of PM-induced health effects that largely remains to be determined, and mechanistic understanding on the toxicological effects of ambient ultrafine particles and nanomaterials will be the focus of studies in the near future.",2016 Dec 8,"['Xia, Tian', 'Zhu, Yifang', 'Mu, Lina', 'Zhang, Zuo-Feng', 'Liu, Sijin']",Natl Sci Rev,,,True
32e54e86db8e7cc46844319fb3dba6d9a02a86f7,PMC,Protecting an island nation from extreme pandemic threats: Proof-of-concept around border closure as an intervention,http://dx.doi.org/10.1371/journal.pone.0178732,PMC5473559,28622344,CC BY,"BACKGROUND: Countries are well advised to prepare for future pandemic risks (e.g., pandemic influenza, novel emerging agents or synthetic bioweapons). These preparations do not typically include planning for complete border closure. Even though border closure may not be instituted in time, and can fail, there might still plausible chances of success for well organized island nations. OBJECTIVE: To estimate costs and benefits of complete border closure in response to new pandemic threats, at an initial proof-of-concept level. New Zealand was used as a case-study for an island country. METHODS: An Excel spreadsheet model was developed to estimate costs and benefits. Case-study specific epidemiological data was sourced from past influenza pandemics. Country-specific healthcare cost data, valuation of life, and lost tourism revenue were imputed (with lost trade also in scenario analyses). RESULTS: For a new pandemic equivalent to the 1918 influenza pandemic (albeit with half the mortality rate, “Scenario A”), it was estimated that successful border closure for 26 weeks provided a net societal benefit (e.g., of NZ$11.0 billion, USD$7.3 billion). Even in the face of a complete end to trade, a net benefit was estimated for scenarios where the mortality rate was high (e.g., at 10 times the mortality impact of “Scenario A”, or 2.75% of the country’s population dying) giving a net benefit of NZ$54 billion (USD$36 billion). But for some other pandemic scenarios where trade ceased, border closure resulted in a net negative societal value (e.g., for “Scenario A” times three for 26 weeks of border closure–but not for only 12 weeks of closure when it would still be beneficial). CONCLUSIONS: This “proof-of-concept” work indicates that more detailed cost-benefit analysis of border closure in very severe pandemic situations for some island nations is probably warranted, as this course of action might sometimes be worthwhile from a societal perspective.",2017 Jun 16,"['Boyd, Matt', 'Baker, Michael G.', 'Mansoor, Osman D.', 'Kvizhinadze, Giorgi', 'Wilson, Nick']",PLoS One,,,True
a309fbcf24f3b728a280f67805614ddffca0f8c7,PMC,Back to the Future: Multiparent Populations Provide the Key to Unlocking the Genetic Basis of Complex Traits,http://dx.doi.org/10.1534/g3.117.042846,PMC5473742,28592643,CC BY,,2017 Jun 5,"['de Koning, Dirk-Jan', 'McIntyre, Lauren M.']",G3 (Bethesda),,,True
18b07e5bf3382f2c2e74f95e20571f32c07553b0,PMC,Inbred Strain Variant Database (ISVdb): A Repository for Probabilistically Informed Sequence Differences Among the Collaborative Cross Strains and Their Founders,http://dx.doi.org/10.1534/g3.117.041491,PMC5473744,28592645,CC BY,"The Collaborative Cross (CC) is a panel of recently established multiparental recombinant inbred mouse strains. For the CC, as for any multiparental population (MPP), effective experimental design and analysis benefit from detailed knowledge of the genetic differences between strains. Such differences can be directly determined by sequencing, but until now whole-genome sequencing was not publicly available for individual CC strains. An alternative and complementary approach is to infer genetic differences by combining two pieces of information: probabilistic estimates of the CC haplotype mosaic from a custom genotyping array, and probabilistic variant calls from sequencing of the CC founders. The computation for this inference, especially when performed genome-wide, can be intricate and time-consuming, requiring the researcher to generate nontrivial and potentially error-prone scripts. To provide standardized, easy-to-access CC sequence information, we have developed the Inbred Strain Variant Database (ISVdb). The ISVdb provides, for all the exonic variants from the Sanger Institute mouse sequencing dataset, direct sequence information for CC founders and, critically, the imputed sequence information for CC strains. Notably, the ISVdb also: (1) provides predicted variant consequence metadata; (2) allows rapid simulation of F1 populations; and (3) preserves imputation uncertainty, which will allow imputed data to be refined in the future as additional sequencing and genotyping data are collected. The ISVdb information is housed in an SQL database and is easily accessible through a custom online interface (http://isvdb.unc.edu), reducing the analytic burden on any researcher using the CC.",2017 Jun 5,"['Oreper, Daniel', 'Cai, Yanwei', 'Tarantino, Lisa M.', 'de Villena, Fernando Pardo-Manuel', 'Valdar, William']",G3 (Bethesda),,,False
942326084a2892419bebfb4508ed7158c158fac9,PMC,Inbred Strain Variant Database (ISVdb): A Repository for Probabilistically Informed Sequence Differences Among the Collaborative Cross Strains and Their Founders,http://dx.doi.org/10.1534/g3.117.041491,PMC5473744,28592645,CC BY,"The Collaborative Cross (CC) is a panel of recently established multiparental recombinant inbred mouse strains. For the CC, as for any multiparental population (MPP), effective experimental design and analysis benefit from detailed knowledge of the genetic differences between strains. Such differences can be directly determined by sequencing, but until now whole-genome sequencing was not publicly available for individual CC strains. An alternative and complementary approach is to infer genetic differences by combining two pieces of information: probabilistic estimates of the CC haplotype mosaic from a custom genotyping array, and probabilistic variant calls from sequencing of the CC founders. The computation for this inference, especially when performed genome-wide, can be intricate and time-consuming, requiring the researcher to generate nontrivial and potentially error-prone scripts. To provide standardized, easy-to-access CC sequence information, we have developed the Inbred Strain Variant Database (ISVdb). The ISVdb provides, for all the exonic variants from the Sanger Institute mouse sequencing dataset, direct sequence information for CC founders and, critically, the imputed sequence information for CC strains. Notably, the ISVdb also: (1) provides predicted variant consequence metadata; (2) allows rapid simulation of F1 populations; and (3) preserves imputation uncertainty, which will allow imputed data to be refined in the future as additional sequencing and genotyping data are collected. The ISVdb information is housed in an SQL database and is easily accessible through a custom online interface (http://isvdb.unc.edu), reducing the analytic burden on any researcher using the CC.",2017 Jun 5,"['Oreper, Daniel', 'Cai, Yanwei', 'Tarantino, Lisa M.', 'de Villena, Fernando Pardo-Manuel', 'Valdar, William']",G3 (Bethesda),,,True
6d5c9139359f0be11be696bec88268a4f1cf7131,PMC,Allelic Variation in the Toll-Like Receptor Adaptor Protein Ticam2 Contributes to SARS-Coronavirus Pathogenesis in Mice,http://dx.doi.org/10.1534/g3.117.041434,PMC5473747,28592648,CC BY,"Host genetic variation is known to contribute to differential pathogenesis following infection. Mouse models allow direct assessment of host genetic factors responsible for susceptibility to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV). Based on an assessment of early stage lines from the Collaborative Cross mouse multi-parent population, we identified two lines showing highly divergent susceptibilities to SARS-CoV: the resistant CC003/Unc and the susceptible CC053/Unc. We generated 264 F2 mice between these strains, and infected them with SARS-CoV. Weight loss, pulmonary hemorrhage, and viral load were all highly correlated disease phenotypes. We identified a quantitative trait locus of major effect on chromosome 18 (27.1–58.6 Mb) which affected weight loss, viral titer and hemorrhage. Additionally, each of these three phenotypes had distinct quantitative trait loci [Chr 9 (weight loss), Chrs 7 and 12 (virus titer), and Chr 15 (hemorrhage)]. We identified Ticam2, an adaptor protein in the TLR signaling pathways, as a candidate driving differential disease at the Chr 18 locus. Ticam2(−/−) mice were highly susceptible to SARS-CoV infection, exhibiting increased weight loss and more pulmonary hemorrhage than control mice. These results indicate a critical role for Ticam2 in SARS-CoV disease, and highlight the importance of host genetic variation in disease responses.",2017 Jun 5,"['Gralinski, Lisa E.', 'Menachery, Vineet D.', 'Morgan, Andrew P.', 'Totura, Allison L.', 'Beall, Anne', 'Kocher, Jacob', 'Plante, Jessica', 'Harrison-Shostak, D. Corinne', 'Schäfer, Alexandra', 'Pardo-Manuel de Villena, Fernando', 'Ferris, Martin T.', 'Baric, Ralph S.']",G3 (Bethesda),,,True
2eca8ab4bcce2dd3336ae5e3bd05868c6909a117,PMC,Oas1b-dependent Immune Transcriptional Profiles of West Nile Virus Infection in the Collaborative Cross,http://dx.doi.org/10.1534/g3.117.041624,PMC5473748,28592649,CC BY,"The oligoadenylate-synthetase (Oas) gene locus provides innate immune resistance to virus infection. In mouse models, variation in the Oas1b gene influences host susceptibility to flavivirus infection. However, the impact of Oas variation on overall innate immune programming and global gene expression among tissues and in different genetic backgrounds has not been defined. We examined how Oas1b acts in spleen and brain tissue to limit West Nile virus (WNV) susceptibility and disease across a range of genetic backgrounds. The laboratory founder strains of the mouse Collaborative Cross (CC) (A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, and NZO/HlLtJ) all encode a truncated, defective Oas1b, whereas the three wild-derived inbred founder strains (CAST/EiJ, PWK/PhJ, and WSB/EiJ) encode a full-length OAS1B protein. We assessed disease profiles and transcriptional signatures of F1 hybrids derived from these founder strains. F1 hybrids included wild-type Oas1b (F/F), homozygous null Oas1b (N/N), and heterozygous offspring of both parental combinations (F/N and N/F). These mice were challenged with WNV, and brain and spleen samples were harvested for global gene expression analysis. We found that the Oas1b haplotype played a role in WNV susceptibility and disease metrics, but the presence of a functional Oas1b allele in heterozygous offspring did not absolutely predict protection against disease. Our results indicate that Oas1b status as wild-type or truncated, and overall Oas1b gene dosage, link with novel innate immune gene signatures that impact specific biological pathways for the control of flavivirus infection and immunity through both Oas1b-dependent and independent processes.",2017 Jun 5,"['Green, Richard', 'Wilkins, Courtney', 'Thomas, Sunil', 'Sekine, Aimee', 'Hendrick, Duncan M.', 'Voss, Kathleen', 'Ireton, Renee C.', 'Mooney, Michael', 'Go, Jennifer T.', 'Choonoo, Gabrielle', 'Jeng, Sophia', 'de Villena, Fernando Pardo-Manuel', 'Ferris, Martin T.', 'McWeeney, Shannon', 'Gale, Michael']",G3 (Bethesda),,,False
a6e5eab626d98db430e725caeec26c95ee086f86,PMC,Oas1b-dependent Immune Transcriptional Profiles of West Nile Virus Infection in the Collaborative Cross,http://dx.doi.org/10.1534/g3.117.041624,PMC5473748,28592649,CC BY,"The oligoadenylate-synthetase (Oas) gene locus provides innate immune resistance to virus infection. In mouse models, variation in the Oas1b gene influences host susceptibility to flavivirus infection. However, the impact of Oas variation on overall innate immune programming and global gene expression among tissues and in different genetic backgrounds has not been defined. We examined how Oas1b acts in spleen and brain tissue to limit West Nile virus (WNV) susceptibility and disease across a range of genetic backgrounds. The laboratory founder strains of the mouse Collaborative Cross (CC) (A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, and NZO/HlLtJ) all encode a truncated, defective Oas1b, whereas the three wild-derived inbred founder strains (CAST/EiJ, PWK/PhJ, and WSB/EiJ) encode a full-length OAS1B protein. We assessed disease profiles and transcriptional signatures of F1 hybrids derived from these founder strains. F1 hybrids included wild-type Oas1b (F/F), homozygous null Oas1b (N/N), and heterozygous offspring of both parental combinations (F/N and N/F). These mice were challenged with WNV, and brain and spleen samples were harvested for global gene expression analysis. We found that the Oas1b haplotype played a role in WNV susceptibility and disease metrics, but the presence of a functional Oas1b allele in heterozygous offspring did not absolutely predict protection against disease. Our results indicate that Oas1b status as wild-type or truncated, and overall Oas1b gene dosage, link with novel innate immune gene signatures that impact specific biological pathways for the control of flavivirus infection and immunity through both Oas1b-dependent and independent processes.",2017 Jun 5,"['Green, Richard', 'Wilkins, Courtney', 'Thomas, Sunil', 'Sekine, Aimee', 'Hendrick, Duncan M.', 'Voss, Kathleen', 'Ireton, Renee C.', 'Mooney, Michael', 'Go, Jennifer T.', 'Choonoo, Gabrielle', 'Jeng, Sophia', 'de Villena, Fernando Pardo-Manuel', 'Ferris, Martin T.', 'McWeeney, Shannon', 'Gale, Michael']",G3 (Bethesda),,,True
f4f9ea9e0aeb74d3601ee316b84292638c59cc53,PMC,Prediction of lncRNA-protein interactions using HeteSim scores based on heterogeneous networks,http://dx.doi.org/10.1038/s41598-017-03986-1,PMC5473862,28623317,CC BY,"Massive studies have indicated that long non-coding RNAs (lncRNAs) are critical for the regulation of cellular biological processes by binding with RNA-related proteins. However, only a few experimentally supported lncRNA-protein associations have been reported. Existing network-based methods are typically focused on intrinsic features of lncRNA and protein but ignore the information implicit in the topologies of biological networks associated with lncRNAs. Considering the limitations in previous methods, we propose PLPIHS, an effective computational method for Predicting lncRNA-Protein Interactions using HeteSim Scores. PLPIHS uses the HeteSim measure to calculate the relatedness score for each lncRNA-protein pair in the heterogeneous network, which consists of lncRNA-lncRNA similarity network, lncRNA-protein association network and protein-protein interaction network. An SVM classifier to predict lncRNA-protein interactions is built with the HeteSim scores. The results show that PLPIHS performs significantly better than the existing state-of-the-art approaches and achieves an AUC score of 0.97 in the leave-one-out validation test. We also compare the performances of networks with different connectivity density and find that PLPIHS performs well across all the networks. Furthermore, we use the proposed method to identify the related proteins for lncRNA MALAT1. Highly-ranked proteins are verified by the biological studies and demonstrate the effectiveness of our method.",2017 Jun 16,"['Xiao, Yun', 'Zhang, Jingpu', 'Deng, Lei']",Sci Rep,,,True
62bd8c44c827603bc80a41b75fa8ba219969d48a,PMC,Genome-wide analysis of codon usage bias in Bovine Coronavirus,http://dx.doi.org/10.1186/s12985-017-0780-y,PMC5474002,28623921,CC BY,"BACKGROUND: Bovine coronavirus (BCoV) belong to the genus Betacoronavirus of the family Coronaviridae. BCoV are widespread around the world and cause enteric or respiratory infections among cattle, leading to important economic losses to the beef and dairy industry worldwide. To study the relation of codon usage among viruses and their hosts is essential to understand host-pathogen interaction, evasion from host’s immune system and evolution. METHODS: We performed a comprehensive analysis of codon usage and composition of BCoV. RESULTS: The global codon usage among BCoV strains is similar. Significant differences of codon preferences in BCoV genes in relation to codon usage of Bos taurus host genes were found. Most of the highly frequent codons are U-ending. G + C compositional constraint and dinucleotide composition also plays a role in the overall pattern of BCoV codon usage. CONCLUSIONS: The results of these studies revealed that mutational bias is a leading force shaping codon usage in this virus. Additionally, relative dinucleotide frequencies, geographical distribution, and evolutionary processes also influenced the codon usage pattern. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-017-0780-y) contains supplementary material, which is available to authorized users.",2017 Jun 17,"['Castells, Matías', 'Victoria, Matías', 'Colina, Rodney', 'Musto, Héctor', 'Cristina, Juan']",Virol J,,,True
9ec445cf691671bf14bc883bbb07dc5b3e8026b4,PMC,Recurrent and Sustained Viral Infections in Primary Immunodeficiencies,http://dx.doi.org/10.3389/fimmu.2017.00665,PMC5474473,28674531,CC BY,"Viral infections are commonplace and often innocuous. Nevertheless, within the population of patients with primary immunodeficiencies (PIDDs), viral infections can be the feature that drives a diagnostic evaluation or can be the most significant morbidity for the patient. This review is focused on the viral complications of PIDDs. It will focus on respiratory viruses, the most common type of viral infection in the general population. Children and adults with an increased frequency or severity of respiratory viral infections are often referred for an immunologic evaluation. The classic teaching is to investigate humoral function in people with recurrent sinopulmonary infections, but this is often interpreted to mean recurrent bacterial infections. Recurrent or very severe viral infections may also be a harbinger of a primary immunodeficiency as well. This review will also cover persistent cutaneous viral infections, systemic infections, central nervous system infections, and gastrointestinal infections. In each case, the specific viral infections may drive a diagnostic evaluation that is specific for that type of virus. This review also discusses the management of these infections, which can become problematic in patients with PIDDs.",2017 Jun 19,"['Ruffner, Melanie A.', 'Sullivan, Kathleen E.', 'Henrickson, Sarah E.']",Front Immunol,,,True
e332700e155cc5fdda4cb03b94d23df42647911b,PMC,Quantitative phosphoproteome on the silkworm (Bombyx mori) cells infected with baculovirus,http://dx.doi.org/10.1186/s12985-017-0783-8,PMC5477107,28629377,CC BY,"BACKGROUND: Bombyx mori has become an important model organism for many fundamental studies. Bombyx mori nucleopolyhedrovirus (BmNPV) is a significant pathogen to Bombyx mori, yet also an efficient vector for recombinant protein production. A previous study indicated that acetylation plays many vital roles in several cellular processes of Bombyx mori while global phosphorylation pattern upon BmNPV infection remains elusive. METHOD: Employing tandem mass tag (TMT) labeling and phosphorylation affinity enrichment followed by high-resolution LC-MS/MS analysis and intensive bioinformatics analysis, the quantitative phosphoproteome in Bombyx mori cells infected by BmNPV at 24 hpi with an MOI of 10 was extensively examined. RESULTS: Totally, 6480 phosphorylation sites in 2112 protein groups were identified, among which 4764 sites in 1717 proteins were quantified. Among the quantified proteins, 81 up-regulated and 25 down-regulated sites were identified with significant criteria (the quantitative ratio above 1.3 was considered as up-regulation and below 0.77 was considered as down-regulation) and with significant p-value (p < 0.05). Some proteins of BmNPV were also hyperphosphorylated during infection, such as P6.9, 39 K, LEF-6, Ac58-like protein, Ac82-like protein and BRO-D. CONCLUSION: The phosphorylated proteins were primary involved in several specific functions, out of which, we focused on the binding activity, protein synthesis, viral replication and apoptosis through kinase activity.",2017 Jun 19,"['Shobahah, Jauharotus', 'Xue, Shengjie', 'Hu, Dongbing', 'Zhao, Cui', 'Wei, Ming', 'Quan, Yanping', 'Yu, Wei']",Virol J,,,True
57cfa4c490208b9a56470ca156fd18ba8b813cc1,PMC,Complete Genome Sequences of Porcine Deltacoronavirus Strains DH1/2016 and DH2/2016 Isolated in South Korea,http://dx.doi.org/10.1128/genomeA.01706-16,PMC5477201,28473399,CC BY,"Two porcine deltacoronavirus (PDCoV) strains, named DH1/2016 and DH2/2016, were isolated from feces of piglets which had severe watery diarrhea symptoms. A comparison of the complete genome sequences suggested that the DH1/2016 and DH2/2016 strains are highly homologous to each other and to PDCoVs isolated in early 2014 from the United States.",2017 May 4,"['Chung, Hee-Chun', 'Nguyen, Van Giap', 'Oh, Woo-Taek', 'My Le, Huynh Thi', 'Moon, Hyung-Joon', 'Lee, Jee-Hoon', 'Kim, Hye-Kwon', 'Park, Seong-Jun', 'Park, Bong Kyun']",Genome Announc,,,True
eef0ecf5b8e7b179dadaef967e65f2ab68f021e1,PMC,First Complete Genome Sequence of a French Bovine coronavirus Strain,http://dx.doi.org/10.1128/genomeA.00319-17,PMC5477389,28546476,CC BY,We sequenced the first Bovine coronavirus (BCoV) complete genome sequence from France. This BCoV was directly sequenced from a fecal sample collected from a calf in Normandy in 2014.,2017 May 25,"['Kin, Nathalie', 'Guerard, Pauline', 'Diancourt, Laure', 'Caro, Valérie', 'Vabret, Astrid', 'Ar Gouilh, Meriadeg']",Genome Announc,,,True
589fe7dd846e7bbab5e7d6dacf7fab2ca6c4f340,PMC,Movement and contact patterns of long-distance free-grazing ducks and avian influenza persistence in Vietnam,http://dx.doi.org/10.1371/journal.pone.0178241,PMC5478089,28632789,CC BY,"Presence of ducks, and in particular of free-grazing ducks, has consistently been shown to be one of the most important risk factors for highly pathogenic avian influenza outbreaks which has compromised poultry production in South-East Asia since the early 2000s and continues to threaten public health, farmers’ livelihood and food security. Although free-grazing duck production has been practised for decades in South-East Asia, there are few published studies describing this production system, which is suspected to play an important role in the maintenance of avian influenza viruses. This study aimed at describing quantitatively the long-distance free-grazing duck production system in South Vietnam, characterising the movement and contact patterns of the duck flocks, and identifying potential associations between farming practices, movement and contact patterns and the circulation of avian influenza viruses. We conducted interviews among stakeholders involved in the free-grazing duck production system (duck farmers, transporters and rice paddy owners) in combination with a virological cross-sectional survey in South Vietnam. Results show that both direct and indirect contacts between free-grazing duck flocks were frequent and diverse. The flocks were transported extensively across district and province boundaries, mainly by boat but also by truck or on foot. A third of the investigated flocks had a positive influenza A virology test, indicating current circulation of avian influenza viruses, but none were positive for H5 subtypes. The age and size of the flock as well as its location at the time of sampling were associated with the risk of influenza A circulation in the flocks. These findings should be considered when developing risk assessment models of influenza virus spread aimed at informing the development of improved biosecurity practices leading to enhanced animal health, sustainable animal production and reliable income for farmers.",2017 Jun 20,"['Meyer, Anne', 'Dinh, Tung Xuan', 'Nhu, Thu Van', 'Pham, Long Thanh', 'Newman, Scott', 'Nguyen, Thuy Thi Thanh', 'Pfeiffer, Dirk Udo', 'Vergne, Timothée']",PLoS One,,,True
57397b8f3a646e2995f974685d05b925a8349824,PMC,Movement and contact patterns of long-distance free-grazing ducks and avian influenza persistence in Vietnam,http://dx.doi.org/10.1371/journal.pone.0178241,PMC5478089,28632789,CC BY,"Presence of ducks, and in particular of free-grazing ducks, has consistently been shown to be one of the most important risk factors for highly pathogenic avian influenza outbreaks which has compromised poultry production in South-East Asia since the early 2000s and continues to threaten public health, farmers’ livelihood and food security. Although free-grazing duck production has been practised for decades in South-East Asia, there are few published studies describing this production system, which is suspected to play an important role in the maintenance of avian influenza viruses. This study aimed at describing quantitatively the long-distance free-grazing duck production system in South Vietnam, characterising the movement and contact patterns of the duck flocks, and identifying potential associations between farming practices, movement and contact patterns and the circulation of avian influenza viruses. We conducted interviews among stakeholders involved in the free-grazing duck production system (duck farmers, transporters and rice paddy owners) in combination with a virological cross-sectional survey in South Vietnam. Results show that both direct and indirect contacts between free-grazing duck flocks were frequent and diverse. The flocks were transported extensively across district and province boundaries, mainly by boat but also by truck or on foot. A third of the investigated flocks had a positive influenza A virology test, indicating current circulation of avian influenza viruses, but none were positive for H5 subtypes. The age and size of the flock as well as its location at the time of sampling were associated with the risk of influenza A circulation in the flocks. These findings should be considered when developing risk assessment models of influenza virus spread aimed at informing the development of improved biosecurity practices leading to enhanced animal health, sustainable animal production and reliable income for farmers.",2017 Jun 20,"['Meyer, Anne', 'Dinh, Tung Xuan', 'Nhu, Thu Van', 'Pham, Long Thanh', 'Newman, Scott', 'Nguyen, Thuy Thi Thanh', 'Pfeiffer, Dirk Udo', 'Vergne, Timothée']",PLoS One,,,False
66bc28b8a963167673e28c9199c15038f8d39742,PMC,Movement and contact patterns of long-distance free-grazing ducks and avian influenza persistence in Vietnam,http://dx.doi.org/10.1371/journal.pone.0178241,PMC5478089,28632789,CC BY,"Presence of ducks, and in particular of free-grazing ducks, has consistently been shown to be one of the most important risk factors for highly pathogenic avian influenza outbreaks which has compromised poultry production in South-East Asia since the early 2000s and continues to threaten public health, farmers’ livelihood and food security. Although free-grazing duck production has been practised for decades in South-East Asia, there are few published studies describing this production system, which is suspected to play an important role in the maintenance of avian influenza viruses. This study aimed at describing quantitatively the long-distance free-grazing duck production system in South Vietnam, characterising the movement and contact patterns of the duck flocks, and identifying potential associations between farming practices, movement and contact patterns and the circulation of avian influenza viruses. We conducted interviews among stakeholders involved in the free-grazing duck production system (duck farmers, transporters and rice paddy owners) in combination with a virological cross-sectional survey in South Vietnam. Results show that both direct and indirect contacts between free-grazing duck flocks were frequent and diverse. The flocks were transported extensively across district and province boundaries, mainly by boat but also by truck or on foot. A third of the investigated flocks had a positive influenza A virology test, indicating current circulation of avian influenza viruses, but none were positive for H5 subtypes. The age and size of the flock as well as its location at the time of sampling were associated with the risk of influenza A circulation in the flocks. These findings should be considered when developing risk assessment models of influenza virus spread aimed at informing the development of improved biosecurity practices leading to enhanced animal health, sustainable animal production and reliable income for farmers.",2017 Jun 20,"['Meyer, Anne', 'Dinh, Tung Xuan', 'Nhu, Thu Van', 'Pham, Long Thanh', 'Newman, Scott', 'Nguyen, Thuy Thi Thanh', 'Pfeiffer, Dirk Udo', 'Vergne, Timothée']",PLoS One,,,False
02aabee05e6968897e1031a767f6658ef0fc7b19,PMC,Movement and contact patterns of long-distance free-grazing ducks and avian influenza persistence in Vietnam,http://dx.doi.org/10.1371/journal.pone.0178241,PMC5478089,28632789,CC BY,"Presence of ducks, and in particular of free-grazing ducks, has consistently been shown to be one of the most important risk factors for highly pathogenic avian influenza outbreaks which has compromised poultry production in South-East Asia since the early 2000s and continues to threaten public health, farmers’ livelihood and food security. Although free-grazing duck production has been practised for decades in South-East Asia, there are few published studies describing this production system, which is suspected to play an important role in the maintenance of avian influenza viruses. This study aimed at describing quantitatively the long-distance free-grazing duck production system in South Vietnam, characterising the movement and contact patterns of the duck flocks, and identifying potential associations between farming practices, movement and contact patterns and the circulation of avian influenza viruses. We conducted interviews among stakeholders involved in the free-grazing duck production system (duck farmers, transporters and rice paddy owners) in combination with a virological cross-sectional survey in South Vietnam. Results show that both direct and indirect contacts between free-grazing duck flocks were frequent and diverse. The flocks were transported extensively across district and province boundaries, mainly by boat but also by truck or on foot. A third of the investigated flocks had a positive influenza A virology test, indicating current circulation of avian influenza viruses, but none were positive for H5 subtypes. The age and size of the flock as well as its location at the time of sampling were associated with the risk of influenza A circulation in the flocks. These findings should be considered when developing risk assessment models of influenza virus spread aimed at informing the development of improved biosecurity practices leading to enhanced animal health, sustainable animal production and reliable income for farmers.",2017 Jun 20,"['Meyer, Anne', 'Dinh, Tung Xuan', 'Nhu, Thu Van', 'Pham, Long Thanh', 'Newman, Scott', 'Nguyen, Thuy Thi Thanh', 'Pfeiffer, Dirk Udo', 'Vergne, Timothée']",PLoS One,,,False
388bf10627c470191554ffe46e7fcddbf00aa054,PMC,Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2,http://dx.doi.org/10.1371/journal.pone.0179177,PMC5479546,28636671,CC BY,"The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) mediates viral entry into target cells. Cleavage and activation of SARS S by a host cell protease is essential for infectious viral entry and the responsible enzymes are potential targets for antiviral intervention. The type II transmembrane serine protease TMPRSS2 cleaves and activates SARS S in cell culture and potentially also in the infected host. Here, we investigated which determinants in SARS S control cleavage and activation by TMPRSS2. We found that SARS S residue R667, a previously identified trypsin cleavage site, is also required for S protein cleavage by TMPRSS2. The cleavage fragments produced by trypsin and TMPRSS2 differed in their decoration with N-glycans, suggesting that these proteases cleave different SARS S glycoforms. Although R667 was required for SARS S cleavage by TMPRSS2, this residue was dispensable for TMPRSS2-mediated S protein activation. Conversely, residue R797, previously reported to be required for SARS S activation by trypsin, was dispensable for S protein cleavage but required for S protein activation by TMPRSS2. Collectively, these results show that different residues in SARS S control cleavage and activation by TMPRSS2, suggesting that these processes are more complex than initially appreciated.",2017 Jun 21,"['Reinke, Lennart Michel', 'Spiegel, Martin', 'Plegge, Teresa', 'Hartleib, Anika', 'Nehlmeier, Inga', 'Gierer, Stefanie', 'Hoffmann, Markus', 'Hofmann-Winkler, Heike', 'Winkler, Michael', 'Pöhlmann, Stefan']",PLoS One,,,True
7d77a852039f1cfc2c13843ecfa721c1fe49528c,PMC,Lung ultrasound as a diagnostic tool for radiographically-confirmed pneumonia in low resource settings,http://dx.doi.org/10.1016/j.rmed.2017.05.007,PMC5480773,28610670,CC BY,"BACKGROUND: Pneumonia is a leading cause of morbidity and mortality in children worldwide; however, its diagnosis can be challenging, especially in settings where skilled clinicians or standard imaging are unavailable. We sought to determine the diagnostic accuracy of lung ultrasound when compared to radiographically-confirmed clinical pediatric pneumonia. METHODS: Between January 2012 and September 2013, we consecutively enrolled children aged 2–59 months with primary respiratory complaints at the outpatient clinics, emergency department, and inpatient wards of the Instituto Nacional de Salud del Niño in Lima, Peru. All participants underwent clinical evaluation by a pediatrician and lung ultrasonography by one of three general practitioners. We also consecutively enrolled children without respiratory symptoms. Children with respiratory symptoms had a chest radiograph. We obtained ancillary laboratory testing in a subset. RESULTS: Final clinical diagnoses included 453 children with pneumonia, 133 with asthma, 103 with bronchiolitis, and 143 with upper respiratory infections. In total, CXR confirmed the diagnosis in 191 (42%) of 453 children with clinical pneumonia. A consolidation on lung ultrasound, which is our primary endpoint for pneumonia, had a sensitivity of 88.5%, specificity of 100%, and an area under-the-curve of 0.94 (95% CI 0.92–0.97) when compared to radiographically-confirmed clinical pneumonia. When any abnormality on lung ultrasound was compared to radiographically-confirmed clinical pneumonia the sensitivity increased to 92.2% and the specificity decreased to 95.2%, with an area under-the-curve of 0.94 (95% CI 0.91–0.96). CONCLUSIONS: Lung ultrasound had high diagnostic accuracy for the diagnosis of radiographically-confirmed pneumonia. Added benefits of lung ultrasound include rapid testing and high inter-rater agreement. Lung ultrasound may serve as an alternative tool for the diagnosis of pediatric pneumonia.",2017 Jul,"['Ellington, Laura E.', 'Gilman, Robert H.', 'Chavez, Miguel A.', 'Pervaiz, Farhan', 'Marin-Concha, Julio', 'Compen-Chang, Patricia', 'Riedel, Stefan', 'Rodriguez, Shalim J.', 'Gaydos, Charlotte', 'Hardick, Justin', 'Tielsch, James M.', 'Steinhoff, Mark', 'Benson, Jane', 'May, Evelyn A.', 'Figueroa-Quintanilla, Dante', 'Checkley, William', None]",Respir Med,,,False
12c3660c37af4a311a3a14667a12ce48388dd6ce,PMC,Contrasting academic and lay press print coverage of the 2013-2016 Ebola Virus Disease outbreak,http://dx.doi.org/10.1371/journal.pone.0179356,PMC5480889,28640889,CC0,"Under a traditional paradigm, only those with the expected background knowledge consume academic literature. The lay press, as well as government and non-government agencies, play a complementary role of extracting findings of high interest or importance and translating them for general viewing. The need for accurate reporting and public advising is paramount when attempting to tackle epidemic outbreaks through behavior change. Yet, public trust in media outlets is at a historic low. The Crisis and Emergency Risk Communication (CERC) model for media reporting on public health emergencies was established in 2005 and has subsequently been used to analyze media reporting on outbreaks of influenza and measles as well as smoking habits and medication compliance. However, no media analysis had yet been performed on the 2013–2016 Ebola Virus Disease (EVD) outbreak. This study compared the EVD information relayed by lay press sources with general review articles in the academic literature through a mixed-methods analysis. These findings suggest that comprehensive review articles could not serve as a source to clarify and contextualize the uncertainties around the EVD outbreak, perhaps due to adherence to technical accuracy at the expense of clarity within the context of outbreak conditions. This finding does not imply inferiority of the academic literature, nor does it draw direct causation between confusion in review articles and public misunderstanding. Given the erosion of the barriers siloing academia, combined with the demands of today’s fast-paced media environment, contemporary researchers should realize that no study is outside the public forum and to therefore consider shifting the paradigm to take personal responsibility in the process of accurately translating their scientific words into public policy actions to best serve as a source of clarity.",2017 Jun 22,"['Kieh, Mark D.', 'Cho, Elim M.', 'Myles, Ian A.']",PLoS One,,,True
1b41bb775aaf552e944aceaa31f52814e264c78d,PMC,A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus,http://dx.doi.org/10.1371/journal.pntd.0005655,PMC5481143,28604797,CC0,"The isolation of neutralizing monoclonal antibodies (nmAbs) against the Zika virus (ZIKV) might lead to novel preventative strategies for infections in at-risk individuals, primarily pregnant women. Here we describe the characterization of human mAbs from the plasmablasts of an acutely infected patient. One of the 18 mAbs had the unusual feature of binding to and neutralizing ZIKV despite not appearing to have been diversified by affinity maturation. This mAb neutralized ZIKV (Neut(50) ~ 2 μg/ml) but did not react with any of the four dengue virus serotypes. Except for the expected junctional diversity created by the joining of the V-(D)-J genes, there was no deviation from immunoglobulin germline genes. This is a rare example of a human mAb with neutralizing activity in the absence of detectable somatic hypermutation. Importantly, binding of this mAb to ZIKV was specifically inhibited by human plasma from ZIKV-exposed individuals, suggesting that it may be of value in a diagnostic setting.",2017 Jun 12,"['Magnani, Diogo M.', 'Silveira, Cassia G. T.', 'Rosen, Brandon C.', 'Ricciardi, Michael J.', 'Pedreño-Lopez, Núria', 'Gutman, Martin J.', 'Bailey, Varian K.', 'Maxwell, Helen S.', 'Domingues, Aline', 'Gonzalez-Nieto, Lucas', 'Avelino-Silva, Vivian I.', 'Trindade, Mateus', 'Nogueira, Juliana', 'Oliveira, Consuelo S.', 'Maestri, Alvino', 'Felix, Alvina Clara', 'Levi, José Eduardo', 'Nogueira, Mauricio L.', 'Martins, Mauricio A.', 'Martinez-Navio, José M.', 'Fuchs, Sebastian P.', 'Whitehead, Stephen S.', 'Burton, Dennis R.', 'Desrosiers, Ronald C.', 'Kallas, Esper G.', 'Watkins, David I.']",PLoS Negl Trop Dis,,,True
dcfec62a72ac79a8c3086fcd4ea205ccb5f3234b,PMC,A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus,http://dx.doi.org/10.1371/journal.pntd.0005655,PMC5481143,28604797,CC0,"The isolation of neutralizing monoclonal antibodies (nmAbs) against the Zika virus (ZIKV) might lead to novel preventative strategies for infections in at-risk individuals, primarily pregnant women. Here we describe the characterization of human mAbs from the plasmablasts of an acutely infected patient. One of the 18 mAbs had the unusual feature of binding to and neutralizing ZIKV despite not appearing to have been diversified by affinity maturation. This mAb neutralized ZIKV (Neut(50) ~ 2 μg/ml) but did not react with any of the four dengue virus serotypes. Except for the expected junctional diversity created by the joining of the V-(D)-J genes, there was no deviation from immunoglobulin germline genes. This is a rare example of a human mAb with neutralizing activity in the absence of detectable somatic hypermutation. Importantly, binding of this mAb to ZIKV was specifically inhibited by human plasma from ZIKV-exposed individuals, suggesting that it may be of value in a diagnostic setting.",2017 Jun 12,"['Magnani, Diogo M.', 'Silveira, Cassia G. T.', 'Rosen, Brandon C.', 'Ricciardi, Michael J.', 'Pedreño-Lopez, Núria', 'Gutman, Martin J.', 'Bailey, Varian K.', 'Maxwell, Helen S.', 'Domingues, Aline', 'Gonzalez-Nieto, Lucas', 'Avelino-Silva, Vivian I.', 'Trindade, Mateus', 'Nogueira, Juliana', 'Oliveira, Consuelo S.', 'Maestri, Alvino', 'Felix, Alvina Clara', 'Levi, José Eduardo', 'Nogueira, Mauricio L.', 'Martins, Mauricio A.', 'Martinez-Navio, José M.', 'Fuchs, Sebastian P.', 'Whitehead, Stephen S.', 'Burton, Dennis R.', 'Desrosiers, Ronald C.', 'Kallas, Esper G.', 'Watkins, David I.']",PLoS Negl Trop Dis,,,False
c364b714f7fd12037d0611c302f46c01f2cc9606,PMC,A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus,http://dx.doi.org/10.1371/journal.pntd.0005655,PMC5481143,28604797,CC0,"The isolation of neutralizing monoclonal antibodies (nmAbs) against the Zika virus (ZIKV) might lead to novel preventative strategies for infections in at-risk individuals, primarily pregnant women. Here we describe the characterization of human mAbs from the plasmablasts of an acutely infected patient. One of the 18 mAbs had the unusual feature of binding to and neutralizing ZIKV despite not appearing to have been diversified by affinity maturation. This mAb neutralized ZIKV (Neut(50) ~ 2 μg/ml) but did not react with any of the four dengue virus serotypes. Except for the expected junctional diversity created by the joining of the V-(D)-J genes, there was no deviation from immunoglobulin germline genes. This is a rare example of a human mAb with neutralizing activity in the absence of detectable somatic hypermutation. Importantly, binding of this mAb to ZIKV was specifically inhibited by human plasma from ZIKV-exposed individuals, suggesting that it may be of value in a diagnostic setting.",2017 Jun 12,"['Magnani, Diogo M.', 'Silveira, Cassia G. T.', 'Rosen, Brandon C.', 'Ricciardi, Michael J.', 'Pedreño-Lopez, Núria', 'Gutman, Martin J.', 'Bailey, Varian K.', 'Maxwell, Helen S.', 'Domingues, Aline', 'Gonzalez-Nieto, Lucas', 'Avelino-Silva, Vivian I.', 'Trindade, Mateus', 'Nogueira, Juliana', 'Oliveira, Consuelo S.', 'Maestri, Alvino', 'Felix, Alvina Clara', 'Levi, José Eduardo', 'Nogueira, Mauricio L.', 'Martins, Mauricio A.', 'Martinez-Navio, José M.', 'Fuchs, Sebastian P.', 'Whitehead, Stephen S.', 'Burton, Dennis R.', 'Desrosiers, Ronald C.', 'Kallas, Esper G.', 'Watkins, David I.']",PLoS Negl Trop Dis,,,False
c381a318060a8b093ebc7911198e0b7c509bf580,PMC,Challenges in developing methods for quantifying the effects of weather and climate on water-associated diseases: A systematic review,http://dx.doi.org/10.1371/journal.pntd.0005659,PMC5481148,28604791,CC BY,"Infectious diseases attributable to unsafe water supply, sanitation and hygiene (e.g. Cholera, Leptospirosis, Giardiasis) remain an important cause of morbidity and mortality, especially in low-income countries. Climate and weather factors are known to affect the transmission and distribution of infectious diseases and statistical and mathematical modelling are continuously developing to investigate the impact of weather and climate on water-associated diseases. There have been little critical analyses of the methodological approaches. Our objective is to review and summarize statistical and modelling methods used to investigate the effects of weather and climate on infectious diseases associated with water, in order to identify limitations and knowledge gaps in developing of new methods. We conducted a systematic review of English-language papers published from 2000 to 2015. Search terms included concepts related to water-associated diseases, weather and climate, statistical, epidemiological and modelling methods. We found 102 full text papers that met our criteria and were included in the analysis. The most commonly used methods were grouped in two clusters: process-based models (PBM) and time series and spatial epidemiology (TS-SE). In general, PBM methods were employed when the bio-physical mechanism of the pathogen under study was relatively well known (e.g. Vibrio cholerae); TS-SE tended to be used when the specific environmental mechanisms were unclear (e.g. Campylobacter). Important data and methodological challenges emerged, with implications for surveillance and control of water-associated infections. The most common limitations comprised: non-inclusion of key factors (e.g. biological mechanism, demographic heterogeneity, human behavior), reporting bias, poor data quality, and collinearity in exposures. Furthermore, the methods often did not distinguish among the multiple sources of time-lags (e.g. patient physiology, reporting bias, healthcare access) between environmental drivers/exposures and disease detection. Key areas of future research include: disentangling the complex effects of weather/climate on each exposure-health outcome pathway (e.g. person-to-person vs environment-to-person), and linking weather data to individual cases longitudinally.",2017 Jun 12,"['Lo Iacono, Giovanni', 'Armstrong, Ben', 'Fleming, Lora E.', 'Elson, Richard', 'Kovats, Sari', 'Vardoulakis, Sotiris', 'Nichols, Gordon L.']",PLoS Negl Trop Dis,,,True
b950247dbac25ce91de13806e102102a757c16ca,PMC,Targeting Coronaviral Replication and Cellular JAK2 Mediated Dominant NF-κB Activation for Comprehensive and Ultimate Inhibition of Coronaviral Activity,http://dx.doi.org/10.1038/s41598-017-04203-9,PMC5481340,28642467,CC BY,"Tylophorine-based compounds exert broad spectral, potent inhibition of coronaviruses. NF-κB activation is a common pro-inflammatory response of host cells to viral infection. The aims of this study were to (i) find an effective combination treatment for coronaviral infections through targeting of the virus per se and cellular NF-κB activity; and (ii) to study the underling mechanisms. We found that tylophorine-based compounds target the TGEV viral RNA and effectively inhibit TGEV replication. NF-κB inhibition also leads to anti-TGEV replication. NF-κB activation induced by TGEV infection was found to be associated with two convergent pathways, IKK-2_IκBα/p65 and JAK2 mediated p65 phosphorylation, in swine testicular cells. JAK2 inhibition either by CYT387 (a JAK family inhibitor) or by silencing JAK2-expression revealed a dominant JAK2 mediated p65 phosphorylation pathway for NF-κB activation and resulted in NF-κB inhibition, which overrode the IκBα regulation via the IKK-2. Finally, tylophorine-based compounds work cooperatively with CYT387 to impart comprehensive anti-TGEV activities. The combination treatment, wherein a tylophorine compound targets TGEV and a JAK2 inhibitor blocks the alternative dominant NF-κB activation mediated by JAK2, is more effective and comprehensive than either one alone and constitutes a feasible approach for the treatment of SARS-CoV or MERS-CoV.",2017 Jun 22,"['Yang, Cheng-Wei', 'Lee, Yue-Zhi', 'Hsu, Hsing-Yu', 'Shih, Chuan', 'Chao, Yu-Sheng', 'Chang, Hwan-You', 'Lee, Shiow-Ju']",Sci Rep,,,True
a259f7115e26c97fee193b205ec7542b1267829b,PMC,Phylogenetic Tracings of Proteome Size Support the Gradual Accretion of Protein Structural Domains and the Early Origin of Viruses from Primordial Cells,http://dx.doi.org/10.3389/fmicb.2017.01178,PMC5481351,28690608,CC BY,"Untangling the origin and evolution of viruses remains a challenging proposition. We recently studied the global distribution of protein domain structures in thousands of completely sequenced viral and cellular proteomes with comparative genomics, phylogenomics, and multidimensional scaling methods. A tree of life describing the evolution of proteomes revealed viruses emerging from the base of the tree as a fourth supergroup of life. A tree of domains indicated an early origin of modern viral lineages from ancient cells that co-existed with the cellular ancestors. However, it was recently argued that the rooting of our trees and the basal placement of viruses was artifactually induced by small genome (proteome) size. Here we show that these claims arise from misunderstanding and misinterpretations of cladistic methodology. Trees are reconstructed unrooted, and thus, their topologies cannot be distorted a posteriori by the rooting methodology. Tracing proteome size in trees and multidimensional views of evolutionary relationships as well as tests of leaf stability and exclusion/inclusion of taxa demonstrated that the smallest proteomes were neither attracted toward the root nor caused any topological distortions of the trees. Simulations confirmed that taxa clustering patterns were independent of proteome size and were determined by the presence of known evolutionary relatives in data matrices, highlighting the need for broader taxon sampling in phylogeny reconstruction. Instead, phylogenetic tracings of proteome size revealed a slowdown in innovation of the structural domain vocabulary and four regimes of allometric scaling that reflected a Heaps law. These regimes explained increasing economies of scale in the evolutionary growth and accretion of kernel proteome repertoires of viruses and cellular organisms that resemble growth of human languages with limited vocabulary sizes. Results reconcile dynamic and static views of domain frequency distributions that are consistent with the axiom of spatiotemporal continuity that is tenet of evolutionary thinking.",2017 Jun 23,"['Nasir, Arshan', 'Kim, Kyung Mo', 'Caetano-Anollés, Gustavo']",Front Microbiol,,,True
d16e1bd4c6cae1bb55dbc695c5e2ba5105a13921,PMC,Molecular mechanisms of severe acute respiratory syndrome (SARS),http://dx.doi.org/10.1186/1465-9921-6-8,PMC548145,15661082,CC BY,"Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. Due to its high morbidity and mortality and widespread occurrence, SARS has evolved as an important respiratory disease which may be encountered everywhere in the world. The virus was identified as the causative agent of SARS due to the efforts of a WHO-led laboratory network. The potential mutability of the SARS-CoV genome may lead to new SARS outbreaks and several regions of the viral genomes open reading frames have been identified which may contribute to the severe virulence of the virus. With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. Vaccination would offer the most attractive approach to prevent new epidemics of SARS, but the development of vaccines is difficult due to missing data on the role of immune system-virus interactions and the potential mutability of the virus. Even in a situation of no new infections, SARS remains a major health hazard, as new epidemics may arise. Therefore, further experimental and clinical research is required to control the disease.",2005 Jan 20,"['Groneberg, David A', 'Hilgenfeld, Rolf', 'Zabel, Peter']",Respir Res,,,True
3f0142baebbc3d27edc90a86eb9e75e975d2f897,PMC,Efficient and unbiased metagenomic recovery of RNA virus genomes from human plasma samples,http://dx.doi.org/10.1038/s41598-017-02239-5,PMC5482852,28646219,CC BY,"RNA viruses cause significant human pathology and are responsible for the majority of emerging zoonoses. Mainstream diagnostic assays are challenged by their intrinsic diversity, leading to false negatives and incomplete characterisation. New sequencing techniques are expanding our ability to agnostically interrogate nucleic acids within diverse sample types, but in the clinical setting are limited by overwhelming host material and ultra-low target frequency. Through selective host RNA depletion and compensatory protocol adjustments for ultra-low RNA inputs, we are able to detect three major blood-borne RNA viruses – HIV, HCV and HEV. We recovered complete genomes and up to 43% of the genome from samples with viral loads of 10(4) and 10(3) IU/ml respectively. Additionally, we demonstrated the utility of this method in detecting and characterising members of diverse RNA virus families within a human plasma background, some present at very low levels. By applying this method to a patient sample series, we have simultaneously determined the full genome of both a novel subtype of HCV genotype 6, and a co-infecting human pegivirus. This method builds upon earlier RNA metagenomic techniques and can play an important role in the surveillance and diagnostics of blood-borne viruses.",2017 Jun 23,"['Manso, Carmen F.', 'Bibby, David F.', 'Mbisa, Jean L.']",Sci Rep,,,False
8966ac6675efb0bad372010ed73b82e30c4f1624,PMC,Efficient and unbiased metagenomic recovery of RNA virus genomes from human plasma samples,http://dx.doi.org/10.1038/s41598-017-02239-5,PMC5482852,28646219,CC BY,"RNA viruses cause significant human pathology and are responsible for the majority of emerging zoonoses. Mainstream diagnostic assays are challenged by their intrinsic diversity, leading to false negatives and incomplete characterisation. New sequencing techniques are expanding our ability to agnostically interrogate nucleic acids within diverse sample types, but in the clinical setting are limited by overwhelming host material and ultra-low target frequency. Through selective host RNA depletion and compensatory protocol adjustments for ultra-low RNA inputs, we are able to detect three major blood-borne RNA viruses – HIV, HCV and HEV. We recovered complete genomes and up to 43% of the genome from samples with viral loads of 10(4) and 10(3) IU/ml respectively. Additionally, we demonstrated the utility of this method in detecting and characterising members of diverse RNA virus families within a human plasma background, some present at very low levels. By applying this method to a patient sample series, we have simultaneously determined the full genome of both a novel subtype of HCV genotype 6, and a co-infecting human pegivirus. This method builds upon earlier RNA metagenomic techniques and can play an important role in the surveillance and diagnostics of blood-borne viruses.",2017 Jun 23,"['Manso, Carmen F.', 'Bibby, David F.', 'Mbisa, Jean L.']",Sci Rep,,,True
75d78749fe0ededfadc860e8c5eb8562ddcc45f3,PMC,Natural immune response to Plasmodium vivax alpha-helical coiled coil protein motifs and its association with the risk of P. vivax malaria,http://dx.doi.org/10.1371/journal.pone.0179863,PMC5484505,28651021,CC BY,"Protein α-helical coiled coil structures are known to induce antibodies able to block critical functions in different pathogens. In a previous study, a total of 50 proteins of Plasmodium vivax erythrocytic asexual stages containing α-helical coiled coil structural motifs were identified in silico, and the corresponding peptides were chemically synthesized. A total of 43 peptides were recognized by naturally acquired antibodies in plasma samples from both Papua New Guinea (PNG) and Colombian adult donors. In this study, the association between IgG antibodies to these peptides and clinical immunity was further explored by measuring total IgG antibody levels to 24 peptides in baseline samples from a longitudinal study of children aged 1–3 years (n = 164) followed for 16 months. Samples were reactive to all peptides tested. Eight peptides were recognized by >50% of individuals, whereas only one peptide had < 20% reactivity. Children infected at baseline were seropositive to 23/24 peptides. No significant association was observed between antibody titers and age or molecular force of infection, suggesting that antibody levels had already reached an equilibrium. There was a strong association between antibody levels to all peptides and protection against P. vivax clinical episodes during the 16 months follow-up. These results suggest that the selected coiled coil antigens might be good markers of both exposure and acquired immunity to P. vivax malaria, and further preclinical investigation should be performed to determine their potential as P. vivax vaccine antigens.",2017 Jun 26,"['Céspedes, Nora', 'Li Wai Suen, Connie S. N.', 'Koepfli, Cristian', 'França, Camila T.', 'Felger, Ingrid', 'Nebie, Issa', 'Arévalo-Herrera, Myriam', 'Mueller, Ivo', 'Corradin, Giampietro', 'Herrera, Sócrates']",PLoS One,,,True
11db2c3bddc384a29eea59421d8c7034a29f1092,PMC,Natural immune response to Plasmodium vivax alpha-helical coiled coil protein motifs and its association with the risk of P. vivax malaria,http://dx.doi.org/10.1371/journal.pone.0179863,PMC5484505,28651021,CC BY,"Protein α-helical coiled coil structures are known to induce antibodies able to block critical functions in different pathogens. In a previous study, a total of 50 proteins of Plasmodium vivax erythrocytic asexual stages containing α-helical coiled coil structural motifs were identified in silico, and the corresponding peptides were chemically synthesized. A total of 43 peptides were recognized by naturally acquired antibodies in plasma samples from both Papua New Guinea (PNG) and Colombian adult donors. In this study, the association between IgG antibodies to these peptides and clinical immunity was further explored by measuring total IgG antibody levels to 24 peptides in baseline samples from a longitudinal study of children aged 1–3 years (n = 164) followed for 16 months. Samples were reactive to all peptides tested. Eight peptides were recognized by >50% of individuals, whereas only one peptide had < 20% reactivity. Children infected at baseline were seropositive to 23/24 peptides. No significant association was observed between antibody titers and age or molecular force of infection, suggesting that antibody levels had already reached an equilibrium. There was a strong association between antibody levels to all peptides and protection against P. vivax clinical episodes during the 16 months follow-up. These results suggest that the selected coiled coil antigens might be good markers of both exposure and acquired immunity to P. vivax malaria, and further preclinical investigation should be performed to determine their potential as P. vivax vaccine antigens.",2017 Jun 26,"['Céspedes, Nora', 'Li Wai Suen, Connie S. N.', 'Koepfli, Cristian', 'França, Camila T.', 'Felger, Ingrid', 'Nebie, Issa', 'Arévalo-Herrera, Myriam', 'Mueller, Ivo', 'Corradin, Giampietro', 'Herrera, Sócrates']",PLoS One,,,False
d0f140c55a5096788d681aa9ab115fba68e0e059,PMC,A Review of Quantitative Tools Used to Assess the Epidemiology of Porcine Reproductive and Respiratory Syndrome in U.S. Swine Farms Using Dr. Morrison’s Swine Health Monitoring Program Data,http://dx.doi.org/10.3389/fvets.2017.00094,PMC5484771,28702459,CC BY,"Porcine reproductive and respiratory syndrome (PRRS) causes far-reaching financial losses to infected countries and regions, including the U.S. The Dr. Morrison’s Swine Health Monitoring Program (MSHMP) is a voluntary initiative in which producers and veterinarians share sow farm PRRS status weekly to contribute to the understanding, in quantitative terms, of PRRS epidemiological dynamics and, ultimately, to support its control in the U.S. Here, we offer a review of a variety of analytic tools that were applied to MSHMP data to assess disease dynamics in quantitative terms to support the decision-making process for veterinarians and producers. Use of those methods has helped the U.S. swine industry to quantify the cyclical patterns of PRRS, to describe the impact that emerging pathogens has had on that pattern, to identify the nature and extent at which environmental factors (e.g., precipitation or land cover) influence PRRS risk, to identify PRRS virus emerging strains, and to assess the influence that voluntary reporting has on disease control. Results from the numerous studies reviewed here provide important insights into PRRS epidemiology that help to create the foundations for a near real-time prediction of disease risk, and, ultimately, will contribute to support the prevention and control of, arguably, one of the most devastating diseases affecting the North American swine industry. The review also demonstrates how different approaches to analyze and visualize the data may help to add value to the routine collection of surveillance data and support infectious animal disease control.",2017 Jun 27,"['Vilalta, Carles', 'Arruda, Andreia G.', 'Tousignant, Steven J. P.', 'Valdes-Donoso, Pablo', 'Muellner, Petra', 'Muellner, Ulrich', 'Alkhamis, Moh A.', 'Morrison, Robert B.', 'Perez, Andres M.']",Front Vet Sci,,,True
0b530925f860fe1a3191519482c19e8240834caf,PMC,miRNA-200c-3p is crucial in acute respiratory distress syndrome,http://dx.doi.org/10.1038/celldisc.2017.21,PMC5485385,28690868,CC BY,"Influenza infection and pneumonia are known to cause much of their mortality by inducing acute respiratory distress syndrome (ARDS), which is the most severe form of acute lung injury (ALI). Angiotensin-converting enzyme 2 (ACE2), which is a negative regulator of angiotensin II in the renin–angiotensin system, has been reported to have a crucial role in ALI. Downregulation of ACE2 is always associated with the ALI or ARDS induced by avian influenza virus, severe acute respiratory syndrome-coronavirus, respiratory syncytial virus and sepsis. However, the molecular mechanism of the decreased expression of ACE2 in ALI is unclear. Here we show that avian influenza virus H5N1 induced the upregulation of miR-200c-3p, which was then demonstrated to target the 3′-untranslated region of ACE2. Then, we found that nonstructural protein 1 and viral RNA of H5N1 contributed to the induction of miR-200c-3p during viral infection. Additionally, the synthetic analog of viral double-stranded RNA (poly (I:C)), bacterial lipopolysaccharide and lipoteichoic acid can all markedly increase the expression of miR-200c-3p in a nuclear factor-κB-dependent manner. Furthermore, markedly elevated plasma levels of miR-200c-3p were observed in severe pneumonia patients. The inhibition of miR-200c-3p ameliorated the ALI induced by H5N1 virus infection in vivo, indicating a potential therapeutic target. Therefore, we identify a shared mechanism of viral and bacterial lung infection-induced ALI/ARDS via nuclear factor-κB-dependent upregulation of miR-200c-3p to reduce ACE2 levels, which leads increased angiotensin II levels and subsequently causes lung injury.",2017 Jun 27,"['Liu, Qiang', 'Du, Jianchao', 'Yu, Xuezhong', 'Xu, Jun', 'Huang, Fengming', 'Li, Xiaoyun', 'Zhang, Cong', 'Li, Xiao', 'Chang, Jiahui', 'Shang, Daozhen', 'Zhao, Yan', 'Tian, Mingyao', 'Lu, Huijun', 'Xu, Jiantao', 'Li, Chang', 'Zhu, Huadong', 'Jin, Ningyi', 'Jiang, Chengyu']",Cell Discov,,,True
74b1dbfe3ba7ce697986fe2306a687565804bfac,PMC,miRNA-200c-3p is crucial in acute respiratory distress syndrome,http://dx.doi.org/10.1038/celldisc.2017.21,PMC5485385,28690868,CC BY,"Influenza infection and pneumonia are known to cause much of their mortality by inducing acute respiratory distress syndrome (ARDS), which is the most severe form of acute lung injury (ALI). Angiotensin-converting enzyme 2 (ACE2), which is a negative regulator of angiotensin II in the renin–angiotensin system, has been reported to have a crucial role in ALI. Downregulation of ACE2 is always associated with the ALI or ARDS induced by avian influenza virus, severe acute respiratory syndrome-coronavirus, respiratory syncytial virus and sepsis. However, the molecular mechanism of the decreased expression of ACE2 in ALI is unclear. Here we show that avian influenza virus H5N1 induced the upregulation of miR-200c-3p, which was then demonstrated to target the 3′-untranslated region of ACE2. Then, we found that nonstructural protein 1 and viral RNA of H5N1 contributed to the induction of miR-200c-3p during viral infection. Additionally, the synthetic analog of viral double-stranded RNA (poly (I:C)), bacterial lipopolysaccharide and lipoteichoic acid can all markedly increase the expression of miR-200c-3p in a nuclear factor-κB-dependent manner. Furthermore, markedly elevated plasma levels of miR-200c-3p were observed in severe pneumonia patients. The inhibition of miR-200c-3p ameliorated the ALI induced by H5N1 virus infection in vivo, indicating a potential therapeutic target. Therefore, we identify a shared mechanism of viral and bacterial lung infection-induced ALI/ARDS via nuclear factor-κB-dependent upregulation of miR-200c-3p to reduce ACE2 levels, which leads increased angiotensin II levels and subsequently causes lung injury.",2017 Jun 27,"['Liu, Qiang', 'Du, Jianchao', 'Yu, Xuezhong', 'Xu, Jun', 'Huang, Fengming', 'Li, Xiaoyun', 'Zhang, Cong', 'Li, Xiao', 'Chang, Jiahui', 'Shang, Daozhen', 'Zhao, Yan', 'Tian, Mingyao', 'Lu, Huijun', 'Xu, Jiantao', 'Li, Chang', 'Zhu, Huadong', 'Jin, Ningyi', 'Jiang, Chengyu']",Cell Discov,,,False
2ce201c2ba233a562ee605a9aa12d2719cfa2beb,PMC,"A cluster of adenovirus type B55 infection in a neurosurgical inpatient department of a general hospital in Guangdong, China",http://dx.doi.org/10.1111/irv.12457,PMC5485872,28488368,CC BY,"BACKGROUND: Human adenovirus type 55 is a re‐emerging human respiratory pathogen that is associated with several respiratory infections outbreaks in military and school populations. In this study, we describe the first HAdV55‐associated hospital outbreak documented in Guangdong, China. METHODS: Active surveillance was conducted in the involved neurosurgical inpatient department. All staff and patients in the involved neurosurgical department were surveyed for any symptoms of fever (≥38°C) and enlarged tonsils during the outbreak period. Throat swabs and demographic information were collected for all cases. For each specimen, assays for common respiratory viruses were performed using one‐step reverse transcription‐polymerase chain reaction. HAdV‐positive samples were inoculated onto Hep‐2 cells for isolation. Hexon genes, fiber genes, penton genes, and whole genomes were sequenced. A phylogenetic tree was constructed. RESULTS AND CONCLUSIONS: Forty‐three cases, including 24 laboratory‐confirmed cases and 19 possible cases, were identified. Nurses had the highest attack rate of infection, with a rate of 36.4%. The attack rate for doctors and inpatients was 20.0% and 16.7%, respectively. HAdV55 was the sole pathogen identified during this outbreak. The hexon, fiber, and penton genes from seven isolated HAdV55 stains were sequenced. All these genes showed 100% homology and fell into the HAdV55 [P14H11F14] cluster, indicating that HAdV55 was the single viral strain for the outbreak. While not conclusive, the epidemic investigation revealed that the outbreak was introduced by nurses from sources outside the hospital. It was likely that a transmission from staff to inpatients had occurred.",2017 Jul 26,"['Yi, Lina', 'Zou, LiRong', 'Lu, Jing', 'Kang, Min', 'Song, Yingchao', 'Su, Juan', 'Zhang, Xin', 'Liang, LiJun', 'Ni, HanZhong', 'Ke, Changwen', 'Wu, Jie']",Influenza Other Respir Viruses,,,True
8c73602b18bc6b2fb17e8f37552995f6e310c6fd,PMC,Therapeutic Applications of Rose Hips from Different Rosa Species,http://dx.doi.org/10.3390/ijms18061137,PMC5485961,28587101,CC BY,"Rosa species, rose hips, are widespread wild plants that have been traditionally used as medicinal compounds for the treatment of a wide variety of diseases. The therapeutic potential of these plants is based on its antioxidant effects caused by or associated with its phytochemical composition, which includes ascorbic acid, phenolic compounds and healthy fatty acids among others. Over the last few years, medicinal interest in rose hips has increased as a consequence of recent research that has studied its potential application as a treatment for several diseases including skin disorders, hepatotoxicity, renal disturbances, diarrhoea, inflammatory disorders, arthritis, diabetes, hyperlipidaemia, obesity and cancer. In this review, the role of different species of Rosa in the prevention of treatment of various disorders related to oxidative stress, is examined, focusing on new therapeutic approaches from a molecular point of view.",2017 May 25,"['Mármol, Inés', 'Sánchez-de-Diego, Cristina', 'Jiménez-Moreno, Nerea', 'Ancín-Azpilicueta, Carmen', 'Rodríguez-Yoldi, María Jesús']",Int J Mol Sci,,,True
3345fa1a77d9ad2f4bce48138490e60a462fe18b,PMC,Sugar-Binding Profiles of Chitin-Binding Lectins from the Hevein Family: A Comprehensive Study,http://dx.doi.org/10.3390/ijms18061160,PMC5485984,28556796,CC BY,"Chitin-binding lectins form the hevein family in plants, which are defined by the presence of single or multiple structurally conserved GlcNAc (N-acetylglucosamine)-binding domains. Although they have been used as probes for chito-oligosaccharides, their detailed specificities remain to be investigated. In this study, we analyzed six chitin-binding lectins, DSA, LEL, PWM, STL, UDA, and WGA, by quantitative frontal affinity chromatography. Some novel features were evident: WGA showed almost comparable affinity for pyridylaminated chitotriose and chitotetraose, while LEL and UDA showed much weaker affinity, and DSA, PWM, and STL had no substantial affinity for the former. WGA showed selective affinity for hybrid-type N-glycans harboring a bisecting GlcNAc residue. UDA showed extensive binding to high-mannose type N-glycans, with affinity increasing with the number of Man residues. DSA showed the highest affinity for highly branched N-glycans consisting of type II LacNAc (N-acetyllactosamine). Further, multivalent features of these lectins were investigated by using glycoconjugate and lectin microarrays. The lectins showed substantial binding to immobilized LacNAc as well as chito-oligosaccharides, although the extents to which they bound varied among them. WGA showed strong binding to heavily sialylated glycoproteins. The above observations will help interpret lectin-glycoprotein interactions in histochemical studies and glyco-biomarker investigations.",2017 May 30,"['Itakura, Yoko', 'Nakamura-Tsuruta, Sachiko', 'Kominami, Junko', 'Tateno, Hiroaki', 'Hirabayashi, Jun']",Int J Mol Sci,,,True
598cb2d5c28e701d3f3533d2690dcc2202f10a8d,PMC,Legume Lectins: Proteins with Diverse Applications,http://dx.doi.org/10.3390/ijms18061242,PMC5486065,28604616,CC BY,Lectins are a diverse class of proteins distributed extensively in nature. Among these proteins; legume lectins display a variety of interesting features including antimicrobial; insecticidal and antitumor activities. Because lectins recognize and bind to specific glycoconjugates present on the surface of cells and intracellular structures; they can serve as potential target molecules for developing practical applications in the fields of food; agriculture; health and pharmaceutical research. This review presents the current knowledge of the main structural characteristics of legume lectins and the relationship of structure to the exhibited specificities; provides an overview of their particular antimicrobial; insecticidal and antitumor biological activities and describes possible applications based on the pattern of recognized glyco-targets.,2017 Jun 12,"['Lagarda-Diaz, Irlanda', 'Guzman-Partida, Ana Maria', 'Vazquez-Moreno, Luz']",Int J Mol Sci,,,True
4925de9bb1feab39f0ffda885f95b59fd0e10cc7,PMC,A Review of Zoonotic Infection Risks Associated with the Wild Meat Trade in Malaysia,http://dx.doi.org/10.1007/s10393-017-1229-x,PMC5486459,28332127,CC BY,"The overhunting of wildlife for food and commercial gain presents a major threat to biodiversity in tropical forests and poses health risks to humans from contact with wild animals. Using a recent survey of wildlife offered at wild meat markets in Malaysia as a basis, we review the literature to determine the potential zoonotic infection risks from hunting, butchering and consuming the species offered. We also determine which taxa potentially host the highest number of pathogens and discuss the significant disease risks from traded wildlife, considering how cultural practices influence zoonotic transmission. We identify 51 zoonotic pathogens (16 viruses, 19 bacteria and 16 parasites) potentially hosted by wildlife and describe the human health risks. The Suidae and the Cervidae families potentially host the highest number of pathogens. We conclude that there are substantial gaps in our knowledge of zoonotic pathogens and recommend performing microbial food safety risk assessments to assess the hazards of wild meat consumption. Overall, there may be considerable zoonotic risks to people involved in the hunting, butchering or consumption of wild meat in Southeast Asia, and these should be considered in public health strategies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10393-017-1229-x) contains supplementary material, which is available to authorized users.",2017 Mar 22,"['Cantlay, Jennifer Caroline', 'Ingram, Daniel J.', 'Meredith, Anna L.']",Ecohealth,,,True
0bb181551513e8bfdac02b7936920ac3f50d01c1,PMC,Parallel evolution of influenza across multiple spatiotemporal scales,http://dx.doi.org/10.7554/eLife.26875,PMC5487208,28653624,CC BY,"Viral variants that arise in the global influenza population begin as de novo mutations in single infected hosts, but the evolutionary dynamics that transform within-host variation to global genetic diversity are poorly understood. Here, we demonstrate that influenza evolution within infected humans recapitulates many evolutionary dynamics observed at the global scale. We deep-sequence longitudinal samples from four immunocompromised patients with long-term H3N2 influenza infections. We find parallel evolution across three scales: within individual patients, in different patients in our study, and in the global influenza population. In hemagglutinin, a small set of mutations arises independently in multiple patients. These same mutations emerge repeatedly within single patients and compete with one another, providing a vivid clinical example of clonal interference. Many of these recurrent within-host mutations also reach a high global frequency in the decade following the patient infections. Our results demonstrate surprising concordance in evolutionary dynamics across multiple spatiotemporal scales. DOI: http://dx.doi.org/10.7554/eLife.26875.001",,"['Xue, Katherine S', 'Stevens-Ayers, Terry', 'Campbell, Angela P', 'Englund, Janet A', 'Pergam, Steven A', 'Boeckh, Michael', 'Bloom, Jesse D']",eLife.; 6:e26875,,,True
a4097a2674eed241d6c9d0f0e98e86e037315cfc,PMC,Strengthening health systems for universal health coverage and sustainable development,http://dx.doi.org/10.2471/BLT.16.187476,PMC5487973,28670019,CC BY,,2017 Jul 1,"['Kieny, Marie Paule', 'Bekedam, Henk', 'Dovlo, Delanyo', 'Fitzgerald, James', 'Habicht, Jarno', 'Harrison, Graham', 'Kluge, Hans', 'Lin, Vivian', 'Menabde, Natela', 'Mirza, Zafar', 'Siddiqi, Sameen', 'Travis, Phyllida']",Bull World Health Organ,,,True
034cab326c750ea98f621e9c65371b8f139fbfb4,PMC,Influenza-Omics and the Host Response: Recent Advances and Future Prospects,http://dx.doi.org/10.3390/pathogens6020025,PMC5488659,28604586,CC BY,"Influenza A viruses (IAV) continually evolve and have the capacity to cause global pandemics. Because IAV represents an ongoing threat, identifying novel therapies and host innate immune factors that contribute to IAV pathogenesis is of considerable interest. This review summarizes the relevant literature as it relates to global host responses to influenza infection at both the proteome and transcriptome level. The various-omics infection systems that include but are not limited to ferrets, mice, pigs, and even the controlled infection of humans are reviewed. Discussion focuses on recent advances, remaining challenges, and knowledge gaps as it relates to influenza-omics infection outcomes.",2017 Jun 10,"['Powell, Joshua D.', 'Waters, Katrina M.']",Pathogens,,,True
526876b78f8e3e24f74eb7a1096efa2fb92c07c4,PMC,Novel approaches for Spatial and Molecular Surveillance of Porcine Reproductive and Respiratory Syndrome Virus (PRRSv) in the United States,http://dx.doi.org/10.1038/s41598-017-04628-2,PMC5489505,28659596,CC BY,"The US swine industry has been impaired over the last 25 years by the far-reaching financial losses caused by the porcine reproductive and respiratory syndrome (PRRS). Here, we explored the relations between the spatial risk of PRRS outbreaks and its phylodynamic history in the U.S during 1998–2016 using ORF5 sequences collected from swine farms in the Midwest region. We used maximum entropy and Bayesian phylodynamic models to generate risk maps for PRRS outbreaks and reconstructed the evolutionary history of three selected phylogenetic clades (A, B and C). High-risk areas for PRRS were best-predicted by pig density and climate seasonality and included Minnesota, Iowa and South Dakota. Phylodynamic models demonstrated that the geographical spread of the three clades followed a heterogeneous spatial diffusion process. Furthermore, PRRS viruses were characterized by typical seasonality in their population size. However, endemic strains were characterized by a substantially slower population growth and evolutionary rates, as well as smaller spatial dispersal rates when compared to emerging strains. We demonstrated the prospects of combining inferences derived from two unique analytical methods to inform decisions related to risk-based interventions of an important pathogen affecting one of the largest food animal industries in the world.",2017 Jun 28,"['Alkhamis, Moh A.', 'Arruda, Andreia G.', 'Morrison, Robert B.', 'Perez, Andres M.']",Sci Rep,,,False
1f31c7be736309949bbd0cf4a0c39841f3f67bd6,PMC,Novel approaches for Spatial and Molecular Surveillance of Porcine Reproductive and Respiratory Syndrome Virus (PRRSv) in the United States,http://dx.doi.org/10.1038/s41598-017-04628-2,PMC5489505,28659596,CC BY,"The US swine industry has been impaired over the last 25 years by the far-reaching financial losses caused by the porcine reproductive and respiratory syndrome (PRRS). Here, we explored the relations between the spatial risk of PRRS outbreaks and its phylodynamic history in the U.S during 1998–2016 using ORF5 sequences collected from swine farms in the Midwest region. We used maximum entropy and Bayesian phylodynamic models to generate risk maps for PRRS outbreaks and reconstructed the evolutionary history of three selected phylogenetic clades (A, B and C). High-risk areas for PRRS were best-predicted by pig density and climate seasonality and included Minnesota, Iowa and South Dakota. Phylodynamic models demonstrated that the geographical spread of the three clades followed a heterogeneous spatial diffusion process. Furthermore, PRRS viruses were characterized by typical seasonality in their population size. However, endemic strains were characterized by a substantially slower population growth and evolutionary rates, as well as smaller spatial dispersal rates when compared to emerging strains. We demonstrated the prospects of combining inferences derived from two unique analytical methods to inform decisions related to risk-based interventions of an important pathogen affecting one of the largest food animal industries in the world.",2017 Jun 28,"['Alkhamis, Moh A.', 'Arruda, Andreia G.', 'Morrison, Robert B.', 'Perez, Andres M.']",Sci Rep,,,True
00f7d667e3362066c08f7d6594d1d3b0cb16e08e,PMC,Third Director of the European Centre for Disease Prevention and Control takes office,http://dx.doi.org/10.2807/1560-7917.ES.2017.22.25.30560,PMC5490457,28662765,CC BY,,2017 Jun 22,,Euro Surveill,,,True
dce8be353f8ed76957af86118e1b77fd82f54292,PMC,"Reference gene selection for quantitative real-time PCR analysis in virus infected cells: SARS corona virus, Yellow fever virus, Human Herpesvirus-6, Camelpox virus and Cytomegalovirus infections",http://dx.doi.org/10.1186/1743-422X-2-7,PMC549079,15705200,CC BY,"Ten potential reference genes were compared for their use in experiments investigating cellular mRNA expression of virus infected cells. Human cell lines were infected with Cytomegalovirus, Human Herpesvirus-6, Camelpox virus, SARS coronavirus or Yellow fever virus. The expression levels of these genes and the viral replication were determined by real-time PCR. Genes were ranked by the BestKeeper tool, the GeNorm tool and by criteria we reported previously. Ranking lists of the genes tested were tool dependent. However, over all, β-actin is an unsuitable as reference gene, whereas TATA-Box binding protein and peptidyl-prolyl-isomerase A are stable reference genes for expression studies in virus infected cells.",2005 Feb 10,"['Radonić, Aleksandar', 'Thulke, Stefanie', 'Bae, Hi-Gung', 'Müller, Marcel A', 'Siegert, Wolfgang', 'Nitsche, Andreas']",Virol J,,,True
a7f21bc68611eecc7ea9f57f86ebd7541d77b632,PMC,UK Pigs at the Time of Slaughter: Investigation into the Correlation of Infection with PRRSV and HEV,http://dx.doi.org/10.3390/v9060110,PMC5490802,28598352,CC BY,"Hepatitis E virus (HEV) and porcine reproductive and respiratory syndrome virus (PRRSV) and are both globally prevalent in the pig population. While HEV does not cause clinical disease in pigs, its zoonotic potential has raised concerns in the food safety sector. PRRS has become endemic in the United Kingdom (UK) since its introduction in 1991, and continues to cause considerable economic losses to the swine industry. A better understanding of the current prevalence and diversity of PRRSV and HEV in the UK, and their potential association, is needed to assess risks and target control measures appropriately. This study used plasma, tonsil, and cecal content samples previously collected from pigs in 14 abattoirs in England and Northern Ireland to study the prevalence of several pathogens including PRRSV and HEV. The diversity of PRRSV strains detected in these samples was analyzed by sequencing open reading frame 5 (ORF5), revealing no substantial difference in PRRSV strains from these clinically unaffected pigs relative to those from clinical cases of disease in the UK. Despite the potential immuno-modulatory effect of PRRSV infection, previously demonstrated to affect Salmonella and HEV shedding profiles, no significant association was found between positive PRRSV status and positive HEV status.",2017 Jun 9,"['Frossard, Jean-Pierre', 'Grierson, Sylvia', 'Cheney, Tanya', 'Steinbach, Falko', 'Choudhury, Bhudipa', 'Williamson, Susanna']",Viruses,,,True
83d82d42b92c964ba7bd7bd9f456a16c9d3cbaaf,PMC,Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.3390/v9060148,PMC5490824,28608816,CC BY,"The adaptive immune response is necessary for the development of protective immunity against infectious diseases. Porcine reproductive and respiratory syndrome virus (PRRSV), a genetically heterogeneous and rapidly evolving RNA virus, is the most burdensome pathogen of swine health and wellbeing worldwide. Viral infection induces antigen-specific immunity that ultimately clears the infection. However, the resulting immune memory, induced by virulent or attenuated vaccine viruses, is inconsistently protective against diverse viral strains. The immunological mechanisms by which primary and memory protection are generated and used are not well understood. Here, we summarize current knowledge regarding cellular and humoral components of the adaptive immune response to PRRSV infection that mediate primary and memory immune protection against viruses.",2017 Jun 13,"['Rahe, Michael C.', 'Murtaugh, Michael P.']",Viruses,,,True
2f405ed2109c2b706eb85413816893558100afba,PMC,Interferon-Lambda: A Potent Regulator of Intestinal Viral Infections,http://dx.doi.org/10.3389/fimmu.2017.00749,PMC5491552,28713375,CC BY,"Interferon-lambda (IFN-λ) is a recently described cytokine found to be of critical importance in innate immune regulation of intestinal viruses. Endogenous IFN-λ has potent antiviral effects and has been shown to control multiple intestinal viruses and may represent a factor that contributes to human variability in response to infection. Importantly, recombinant IFN-λ has therapeutic potential against enteric viral infections, many of which lack other effective treatments. In this mini-review, we describe recent advances regarding IFN-λ-mediated regulation of enteric viruses with important clinical relevance including rotavirus, reovirus, and norovirus. We also briefly discuss IFN-λ interactions with other cytokines important in the intestine, and how IFN-λ may play a role in regulation of intestinal viruses by the commensal microbiome. Finally, we indicate currently outstanding questions regarding IFN-λ control of enteric infections that remain to be explored to enhance our understanding of this important immune molecule.",2017 Jun 30,"['Lee, Sanghyun', 'Baldridge, Megan T.']",Front Immunol,,,True
cbd8eed5192247d945644651f0a9de6166992567,PMC,A novel pancoronavirus RT-PCR assay: frequent detection of human coronavirus NL63 in children hospitalized with respiratory tract infections in Belgium,http://dx.doi.org/10.1186/1471-2334-5-6,PMC549190,15686594,CC BY,"BACKGROUND: Four human coronaviruses are currently known to infect the respiratory tract: human coronaviruses OC43 (HCoV-OC43) and 229E (HCoV-229E), SARS associated coronavirus (SARS-CoV) and the recently identified human coronavirus NL63 (HCoV-NL63). In this study we explored the incidence of HCoV-NL63 infection in children diagnosed with respiratory tract infections in Belgium. METHODS: Samples from children hospitalized with respiratory diseases during the winter seasons of 2003 and 2004 were evaluated for the presence of HCoV-NL63 using a optimized pancoronavirus RT-PCR assay. RESULTS: Seven HCoV-NL63 positive samples were identified, six were collected during January/February 2003 and one at the end of February 2004. CONCLUSIONS: Our results support the notation that HCoV-NL63 can cause serious respiratory symptoms in children. Sequence analysis of the S gene showed that our isolates could be classified into two subtypes corresponding to the two prototype HCoV-NL63 sequences isolated in The Netherlands in 1988 and 2003, indicating that these two subtypes may currently be cocirculating.",2005 Feb 1,"['Moës, Elien', 'Vijgen, Leen', 'Keyaerts, Els', 'Zlateva, Kalina', 'Li, Sandra', 'Maes, Piet', 'Pyrc, Krzysztof', 'Berkhout, Ben', 'van der Hoek, Lia', 'Van Ranst, Marc']",BMC Infect Dis,,,True
04dc7b970967766934f12292c0a007ebabe22652,PMC,"Hematopoietic Stem Cell Transplantation in an Infant with Immunodeficiency, Centromeric Instability, and Facial Anomaly Syndrome",http://dx.doi.org/10.3389/fimmu.2017.00773,PMC5491950,28713390,CC BY,"Immunodeficiency, centromeric instability, and facial anomaly (ICF) syndrome is a rare autosomal recessive genetic condition with severe immunodeficiency, which leads to lethal infections if not recognized and treated in early childhood. Up-to-date treatment regimens consist of prophylactic and supportive treatment of the recurrent infections. Here, we report the case of a 1-year-old boy of Moroccan consanguineous parents, who was diagnosed at 4 months of age with ICF syndrome with a homozygous missense mutation in the DNMT3B gene. He was initially admitted to the hospital with recurrent pulmonary infections from the opportunistic pathogen Pneumocystis jirovecii (PJ). Further immunological workup revealed agammaglobulinemia in the presence of B cells. After successful recovery from the PJ pneumonia, he underwent hematopoietic stem cell transplantation (HSCT) from the HLA-matched healthy sister using a chemotherapeutic conditioning regimen consisting of treosulfan, fludarabine, and thiotepa. Other than acute chemotherapy-associated side effects, no serious adverse events occurred. Six months after HSCT immune-reconstitution, he had a stable chimerism with 2.9% autologous portion in the peripheral blood and a normal differential blood cell count, including all immunoglobulin subtypes. This is one of the first cases of successful HSCT in ICF syndrome. Early diagnosis and subsequent HSCT can prevent severe opportunistic infections and cure the immunodeficiency. Centromeric instability and facial anomaly remain unaffected. Although the long-term patient outcome and the neurological development remain to be seen, this curative therapy for immunodeficiency improves life expectancy and quality of life. This case is meant to raise physicians awareness for ICF syndrome and highlight the consideration for HSCT in ICF syndrome early on.",2017 Jun 30,"['Gössling, Katharina L.', 'Schipp, Cyrill', 'Fischer, Ute', 'Babor, Florian', 'Koch, Gerhard', 'Schuster, Friedhelm R.', 'Dietzel-Dahmen, Jutta', 'Wieczorek, Dagmar', 'Borkhardt, Arndt', 'Meisel, Roland', 'Kuhlen, Michaela']",Front Immunol,,,True
6efd9d7ed926ebe9979cc13990888257507e2e19,PMC,Disease Prevention: An Opportunity to Expand Edible Plant-Based Vaccines?,http://dx.doi.org/10.3390/vaccines5020014,PMC5492011,28556800,CC BY,"The lethality of infectious diseases has decreased due to the implementation of crucial sanitary procedures such as vaccination. However, the resurgence of pathogenic diseases in different parts of the world has revealed the importance of identifying novel, rapid, and concrete solutions for control and prevention. Edible vaccines pose an interesting alternative that could overcome some of the constraints of traditional vaccines. The term “edible vaccine” refers to the use of edible parts of a plant that has been genetically modified to produce specific components of a particular pathogen to generate protection against a disease. The aim of this review is to present and critically examine “edible vaccines” as an option for global immunization against pathogenic diseases and their outbreaks and to discuss the necessary steps for their production and control and the list of plants that may already be used as edible vaccines. Additionally, this review discusses the required standards and ethical regulations as well as the advantages and disadvantages associated with this powerful biotechnology tool.",2017 May 30,"['Concha, Christopher', 'Cañas, Raúl', 'Macuer, Johan', 'Torres, María José', 'Herrada, Andrés A.', 'Jamett, Fabiola', 'Ibáñez, Cristian']",Vaccines (Basel),,,True
5614de18ca272845e663e8f0b0e61667851d419c,PMC,Disease Prevention: An Opportunity to Expand Edible Plant-Based Vaccines?,http://dx.doi.org/10.3390/vaccines5020014,PMC5492011,28556800,CC BY,"The lethality of infectious diseases has decreased due to the implementation of crucial sanitary procedures such as vaccination. However, the resurgence of pathogenic diseases in different parts of the world has revealed the importance of identifying novel, rapid, and concrete solutions for control and prevention. Edible vaccines pose an interesting alternative that could overcome some of the constraints of traditional vaccines. The term “edible vaccine” refers to the use of edible parts of a plant that has been genetically modified to produce specific components of a particular pathogen to generate protection against a disease. The aim of this review is to present and critically examine “edible vaccines” as an option for global immunization against pathogenic diseases and their outbreaks and to discuss the necessary steps for their production and control and the list of plants that may already be used as edible vaccines. Additionally, this review discusses the required standards and ethical regulations as well as the advantages and disadvantages associated with this powerful biotechnology tool.",2017 May 30,"['Concha, Christopher', 'Cañas, Raúl', 'Macuer, Johan', 'Torres, María José', 'Herrada, Andrés A.', 'Jamett, Fabiola', 'Ibáñez, Cristian']",Vaccines (Basel),,,False
9cffe5458f4b3268545d147dd3409b165c5f6ba5,PMC,Experimentally confirmed toltrazuril resistance in a field isolate of Cystoisospora suis,http://dx.doi.org/10.1186/s13071-017-2257-7,PMC5492287,28662668,CC BY,"BACKGROUND: Constant treatment regimens with toltrazuril against Cystoisospora suis infection in piglets are being applied in the intensive production systems for the last two decades, but the possibility of resistance development has not been addressed so far despite limited availability of treatment alternatives. Recently, a pig producer in The Netherlands who routinely used toltrazuril complained about diarrhea in suckling piglets in the absence of bacterial and viral pathogens, and oocysts of C. suis could be isolated from feces of affected litters. METHODS: Piglets from two litters were infected with a field isolate of C. suis, Holland-I, and treated with 0 (Holl-Ctrl), 20 (Holl-20) or 30 (Holl-30) mg/kg of body weight (BW) of toltrazuril (Baycox®). The efficacy of toltrazuril was measured by assessment of oocyst excretion, fecal consistency and BW gain. A separate litter was infected with a toltrazuril-susceptible strain of C. suis, Wien-I, and treated with 0 (Wien-Ctrl) or 20 (Wien-20) mg/kg BW of toltrazuril for comparison. RESULTS: Treatment with the recommended (20 mg/kg) dose of toltrazuril completely suppressed oocyst shedding and diarrhea in group Wien-20. The prevalence of oocyst excretion was 100% in the groups infected with Holland-I and 80% in the group Wien-Ctrl. Most days with diarrhea were observed in group Holl-20 with an average of 6.40%, followed by 5.71% in Wien-Ctrl, while in Holl-Ctrl and Holl-30 diarrhea was only seen in 1.79% of the samples (n = 14/piglet). Oocyst excretion, fecal consistency and BW gain did not differ significantly among groups infected with Holland-I, indicating loss of efficacy to toltrazuril. CONCLUSION: Experimental infections and treatment confirmed toltrazuril resistance against the field isolate even at increased dosage. Such isolates are a potential threat to pig production as no other effective and economically sustainable alternative treatment is currently available. In the absence of a standardized protocol for resistance testing in C. suis, regular parasitological examination and, if possible, experimental confirmation should be considered to evaluate the extent and consequences of toltrazuril resistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-017-2257-7) contains supplementary material, which is available to authorized users.",2017 Jun 29,"['Shrestha, Aruna', 'Freudenschuss, Barbara', 'Jansen, Rutger', 'Hinney, Barbara', 'Ruttkowski, Bärbel', 'Joachim, Anja']",Parasit Vectors,,,True
a91c693865733755a406dbca884738a75b886455,PMC,Risk factors associated with diarrhea in Danish commercial mink (Neovison vison) during the pre-weaning period,http://dx.doi.org/10.1186/s13028-017-0312-1,PMC5492706,28662678,CC BY,"BACKGROUND: Pre-weaning diarrhea in mink, also known as “sticky kits”, is a syndrome and outbreaks occur every year on commercial mink farms in all mink producing countries. Morbidity and mortality can be considerable on a farm with huge economic consequences for the farmer as well as compromised welfare for the mink kits. Although efforts have been taken to identify etiologic agents involved in outbreaks, the syndrome is still regarded as multifactorial and recurring problems on the same farms draw attention to management and environmental risk factors. In the pre-weaning period from May to June 2015, a case control study was carried out on 30 Danish mink farms. Data concerning management, biosecurity, hygiene, feed consumption, antibacterial prescription and production efficiency were analyzed. RESULTS: The proportion of 1-year old females, farm size (total number of females), energy supply per female in the late gestation period, and dogs accessing the farm area were significantly associated with being a case farm. Case farms were prescribed almost twice the amount of antibacterials per gestational unit (female and litter) as in control farms. Farmers on case farms spent significantly more time nursing and treating the animals and experienced more females with mastitis compared to farmers on control farms. No significant differences in cleaning practices or hygienic measures between case and control farms were found and there were no differences in drinking water quality, bedding material, composition neither of color types nor in management regarding litter equalization. CONCLUSIONS: Results from this study showed an association between the occurrence of pre-weaning diarrhea on mink farms and parity profile, farm size and feeding intensity in the gestational period. The access of dogs to the farm area was a significant risk factor, but needs further clarification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-017-0312-1) contains supplementary material, which is available to authorized users.",2017 Jun 29,"['Birch, Julie Melsted', 'Agger, Jens Frederik', 'Dahlin, Christina', 'Jensen, Vibeke Frøkjær', 'Hammer, Anne Sofie', 'Struve, Tina', 'Jensen, Henrik Elvang']",Acta Vet Scand,,,True
3083f7cc3a62acaf4a94a4da4eceb84081d70329,PMC,Establishing an ICD-10 code based SARI-surveillance in Germany – description of the system and first results from five recent influenza seasons,http://dx.doi.org/10.1186/s12889-017-4515-1,PMC5493063,28666433,CC BY,"BACKGROUND: Syndromic surveillance of severe acute respiratory infections (SARI) is important to assess seriousness of disease as recommended by WHO for influenza. In 2015 the Robert Koch Institute (RKI) started to collaborate with a private hospital network to develop a SARI surveillance system using case-based data on ICD-10 codes. This first-time description of the system shows its application to the analysis of five influenza seasons. METHODS: Since week 40/2015, weekly updated anonymized data on discharged patients overall and on patients with respiratory illness including ICD-10 codes of primary and secondary diagnoses are transferred from the network data center to RKI. Retrospective datasets were also provided. Our descriptive analysis is based on data of 47 sentinel hospitals collected between weeks 1/2012 to 20/2016. We applied three different SARI case definitions (CD) based on ICD-10 codes for discharge diagnoses of respiratory tract infections (J09 - J22): basic CD (BCD), using only primary diagnoses; sensitive CD (SCD), using primary and secondary diagnoses; timely CD (TCD), using only primary diagnoses of patients hospitalized up to one week. We compared the CD with regard to severity, age distribution and timeliness and with results from the national primary care sentinel system. RESULTS: The 47 sentinel hospitals covered 3.6% of patients discharged from all German hospitals in 2013. The SCD comprised 2.2 times patients as the BCD, and 3.6 times as many as the TCD. Time course of SARI cases corresponded well to results from primary care surveillance and influenza virus circulation. The patients fulfilling the TCD had been completely reported after 3 weeks, which was fastest among the CD. The proportion of SARI cases among patients was highest in the youngest age group of below 5-year-olds. However, the age group 60 years and above contributed most SARI cases. This was irrespective of the CD used. CONCLUSIONS: In general, available data and the implemented reporting system are appropriate to provide timely and reliable information on SARI in inpatients in Germany. Our ICD-10-based approach proved to be useful for fulfilling requirements for SARI surveillance. The exploratory approach gave valuable insights in data structure and emphasized the advantages of different CD.",2017 Jun 30,"['Buda, S.', 'Tolksdorf, K.', 'Schuler, E.', 'Kuhlen, R.', 'Haas, W.']",BMC Public Health,,,True
b30770ae30b35cdfaf0a173863e74e93edbb0329,PMC,"36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016",http://dx.doi.org/10.1186/s13054-016-1208-6,PMC5493079,27885969,CC BY,"P001 - Sepsis impairs the capillary response within hypoxic capillaries and decreases erythrocyte oxygen-dependent ATP efflux R. M. Bateman, M. D. Sharpe, J. E. Jagger, C. G. Ellis P002 - Lower serum immunoglobulin G2 level does not predispose to severe flu. J. Solé-Violán, M. López-Rodríguez, E. Herrera-Ramos, J. Ruíz-Hernández, L. Borderías, J. Horcajada, N. González-Quevedo, O. Rajas, M. Briones, F. Rodríguez de Castro, C. Rodríguez Gallego P003 - Brain protective effects of intravenous immunoglobulin through inhibition of complement activation and apoptosis in a rat model of sepsis F. Esen, G. Orhun, P. Ergin Ozcan, E. Senturk, C. Ugur Yilmaz, N. Orhan, N. Arican, M. Kaya, M. Kucukerden, M. Giris, U. Akcan, S. Bilgic Gazioglu, E. Tuzun P004 - Adenosine a1 receptor dysfunction is associated with leukopenia: A possible mechanism for sepsis-induced leukopenia R. Riff, O. Naamani, A. Douvdevani P005 - Analysis of neutrophil by hyper spectral imaging - A preliminary report R. Takegawa, H. Yoshida, T. Hirose, N. Yamamoto, H. Hagiya, M. Ojima, Y. Akeda, O. Tasaki, K. Tomono, T. Shimazu P006 - Chemiluminescent intensity assessed by eaa predicts the incidence of postoperative infectious complications following gastrointestinal surgery S. Ono, T. Kubo, S. Suda, T. Ueno, T. Ikeda P007 - Serial change of c1 inhibitor in patients with sepsis – A prospective observational study T. Hirose, H. Ogura, H. Takahashi, M. Ojima, J. Kang, Y. Nakamura, T. Kojima, T. Shimazu P008 - Comparison of bacteremia and sepsis on sepsis related biomarkers T. Ikeda, S. Suda, Y. Izutani, T. Ueno, S. Ono P009 - The changes of procalcitonin levels in critical patients with abdominal septic shock during blood purification T. Taniguchi, M. O P010 - Validation of a new sensitive point of care device for rapid measurement of procalcitonin C. Dinter, J. Lotz, B. Eilers, C. Wissmann, R. Lott P011 - Infection biomarkers in primary care patients with acute respiratory tract infections – Comparison of procalcitonin and C-reactive protein M. M. Meili, P. S. Schuetz P012 - Do we need a lower procalcitonin cut off? H. Hawa, M. Sharshir, M. Aburageila, N. Salahuddin P013 - The predictive role of C-reactive protein and procalcitonin biomarkers in central nervous system infections with extensively drug resistant bacteria V. Chantziara, S. Georgiou, A. Tsimogianni, P. Alexandropoulos, A. Vassi, F. Lagiou, M. Valta, G. Micha, E. Chinou, G. Michaloudis P014 - Changes in endotoxin activity assay and procalcitonin levels after direct hemoperfusion with polymyxin-b immobilized fiber A. Kodaira, T. Ikeda, S. Ono, T. Ueno, S. Suda, Y. Izutani, H. Imaizumi P015 - Diagnostic usefullness of combination biomarkers on ICU admission M. V. De la Torre-Prados, A. Garcia-De la Torre, A. Enguix-Armada, A. Puerto-Morlan, V. Perez-Valero, A. Garcia-Alcantara P016 - Platelet function analysis utilising the PFA-100 does not predict infection, bacteraemia, sepsis or outcome in critically ill patients N. Bolton, J. Dudziak, S. Bonney, A. Tridente, P. Nee P017 - Extracellular histone H3 levels are inversely correlated with antithrombin levels and platelet counts and are associated with mortality in sepsis patients G. Nicolaes, M. Wiewel, M. Schultz, K. Wildhagen, J. Horn, R. Schrijver, T. Van der Poll, C. Reutelingsperger P018 - Il-8: is this a more reliable biomarker for sepsis severity than CRP, Procalcitonin, E-selectin, IL-6 and TNF-[alpha] S. Pillai, G. Davies, G. Mills, R. Aubrey, K. Morris, P. Williams, P. Evans P019 - Relation between adrenomedullin and short-term outcome in ICU patients: Results from the frog ICU study E. G. Gayat, J. Struck, A. Cariou, N. Deye, B. Guidet, S. Jabert, J. Launay, M. Legrand, M. Léone, M. Resche-Rigon, E. Vicaut, A. Vieillard-Baron, A. Mebazaa P020 - Impact of disease severity assessment on performance of heparin-binding protein for the prediction of septic shock R. Arnold, M. Capan, A. Linder, P. Akesson P021 - Kinetics and prognostic value of presepsin (sCD14) in septic patients. A pilot study M. Popescu, D. Tomescu P022 - Comparison of CD64 levels performed by the facs and accellix systems C. L. Sprung, R. Calderon Morales, G. Munteanu, E. Orenbuch-Harroch, P. Levin, H. Kasdan, A. Reiter, T. Volker, Y. Himmel, Y. Cohen, J. Meissonnier P023 - Diagnosing sepsis in 5 minutes: Nanofluidic technology study with pancreatic-stone protein (PSP/ reg) L. Girard, F. Rebeaud P024 - How nanotechnology-based approaches could contribute to sepsis prevention, diagnosis and treatment I. Herrmann P025 - Il7r transcriptional expression analysis during septic shock B. Delwarde, E. Peronnet, E. Cerrato, F. Venet, A. Lepape, T. Rimmelé, G. Monneret, J. Textoris P026 - Disbalance of microbial metabolites of aromatic acids affects the severity in critically ill patients N. Beloborodova, V. Moroz, A. Osipov, A. Bedova, Y. Sarshor, A. Pautova, A. Sergeev, E. Chernevskaya P027 - Copeptin predicts 10-year all-cause mortality in community patients J. Odermatt, R. Bolliger, L. Hersberger, M. Ottiger, M. Christ-Crain, B. Mueller, P. Schuetz P028 - Identification of differential proteomic response in septic patients secondary to community and hospital acquired pneumonia N. K. Sharma, A. K. Tashima, M. K. Brunialti, F. R. Machado, M. Assuncao, O. Rigato, R. Salomao P029 - Monocyte HLA-DR expression in community-acquired bacteremic sepsis - dynamics associated to aetiology and prediction of secondary sepsis S. C. Cajander, G. Rasmussen, E. Tina, B. Söderquist, J. Källman, K. Strålin P030 - Soluble B- and T-lymphocyte attenuator: A possible prognostic marker in sepsis A. L. Lange, J. S. Sundén-Cullberg, A. M. Magnuson, O. H. Hultgren P031 - Fractal dimension: A new biomarker for quantifying clot microstructure in patients across the sepsis spectrum G. Davies, S. Pillai, G. Mills, R. Aubrey, K. Morris, P. Williams, P. Evans P032 - Comparison between the new biomarker for coagulation, clot microstructure (Df) with rotational thromboelastometry (ROTEM) in patients across the sepsis spectrum S. Pillai, G. Davies, G. Mills, R. Aubrey, K. Morris, P. Williams, P. Evans P033 - Changes in fibrinolysis across the sepsis spectrum: The use of rotational thromboelastometry (ROTEM) lysis index (LI60) and D-Dimer concentration S. Pillai, G. Davies, G. Mills, R. Aubrey, K. Morris, P. Williams, P. Evans P034 - The intensive care infection score – a promising marker for the prediction of infection and its severity. P. Van der Geest, M. Mohseni, J. Linssen, R. De Jonge, S. Duran, J. Groeneveld P035 - Challenges in the clinical diagnosis of sepsis R. Miller III, B. K. Lopansri, L. C. McHugh, A. Seldon, J. P. Burke P036 - Does zero heat flux thermometry more accurately identify sepsis on intensive care? J. Johnston, R. Reece-Anthony, A. Bond, A. Molokhia P037 - Advancing quality (AQ) sepsis programme: Improving early identification & treatment of sepsis in North West England. C. Mcgrath, E. Nsutebu P038 - Prehospital transport of acute septic patients P. Bank Pedersen, D. Pilsgaard Henriksen, S. Mikkelsen, A. Touborg Lassen P039 - Vasodilatory plant extracts gel as an alternative treatment for fever in critically ill patients R. Tincu, C. Cobilinschi, D. Tomescu, Z. Ghiorghiu, R. Macovei P040 - Host response and outcome of hypothermic sepsis M. A. Wiewel, M. B. Harmon, L. A. Van Vught, B. P. Scicluna, A. J. Hoogendijk, J. Horn, A. H. Zwinderman, O. L. Cremer, M. J. Bonten, M. J. Schultz, T. Van der Poll, N. P. Juffermans, W. J. Wiersinga P041 - Septic shock alert over SIRS criteria has an impact on outcome but needs to be revised G. Eren, Y Tekdos, M. Dogan, O. Acicbe, E. Kaya, O. Hergunsel P042 - Association between previous prescription of βblockers and mortality rate among septic patients: A retrospective observational study S. Alsolamy, G. Ghamdi, L. Alswaidan, S. Alharbi, F. Alenezi, Y. Arabi P043 - Recognition and treatment of sepsis on labour ward– teaching & information resources can improve knowledge J. Heaton, A. Boyce, L. Nolan, J. Johnston, A. Dukoff-Gordon, A. Dean, A. Molokhia P044 - Culture negative sepsis in the ICU – what is unique to this patient population? T. Mann Ben Yehudah P045 - Organ dysfunction in severe sepsis patients identified in administrative data in Germany, 2007-2013 C. Fleischmann, D. Thomas-Rueddel, C. Haas, U. Dennler, K. Reinhart P046 - A comparison of residents’ knowledge regarding; the Surviving Sepsis Campaign 2012 guideline O. Suntornlohanakul, B. Khwannimit P047 - Effectiveness of a septic shock bundle to improve outcomes in the ICU F. Breckenridge, A. Puxty P048 - Dose of norepinephrine in the first 24 hours as a parameter evaluating the effectiveness of treatment in patients with severe sepsis and septic shock P. Szturz, P. Folwarzcny, J. Svancara, R. Kula, P. Sevcik P049 - Norepinephrine or vasopressin + norepinephrine in septic shock. A retrospective series of 39 patients L. Caneva, A. Casazza, E. Bellazzi, S. Marra, L. Pagani, M. Vetere, R. Vanzino, D. Ciprandi, R. Preda, R. Boschi, L. Carnevale P050 - Methylene blue effectiveness as contributory treatment in patients with septic shock V. Lopez, M. Aguilar Arzapalo, L. Barradas, A. Escalante, J. Gongora, M. Cetina P051 - Coagulation disorders in patients with severe sepsis and DIC evaluated with thromboelastometry. B Adamik, D Jakubczyk, A Kübler P052 - Frequency and outcome of early sepsis-associated coagulopathy A. Radford, T. Lee, J. Singer, J. Boyd, D. Fineberg, M. Williams, J. Russell P053 - Assessment of coagulopathy in cancer patients with severe sepsis or septic shock. A case-control pilot study E. Scarlatescu, D. Tomescu, G. Droc, S. Arama P054 - Thromboelastometry in critically ill patients with disseminated intravascular coagulation M. Müller, M. Straat, S. S. Zeerleder, N. P. Juffermans P055 - Cessation of a preexisting chronic antiplatelet therapy is associated with increased mortality rates in severe sepsis and septic shock C. F. Fuchs, C. S. Scheer, S. W. Wauschkuhn, M. V. Vollmer, K. M. Meissner, S. K. Kuhn, K. H. Hahnenkamp, S. R. Rehberg, M. G. Gründling P056 - Neutrophil Extracellular Traps (NETs) production under hypoxic condition N. Yamamoto, M. Ojima, S. Hamaguchi, T. Hirose, Y. Akeda, R. Takegawa, O. Tasaki, T. Shimazu, K. Tomono P057 - Impact of ultraviolet air sterilizer in intensive care unit room, and clinical outcomes of patients E. Gómez-Sánchez, M. Heredia-Rodríguez, E. Álvarez-Fuente, M. Lorenzo-López, E. Gómez-Pesquera, M. Aragón-Camino, P. Liu-Zhu, A. Sánchez-López, A. Hernández-Lozano, M. T. Peláez-Jareño, E. Tamayo P058 - Focus of infection in severe sepsis - comparison of administrative data and prospective cohorts from Germany D. O. Thomas-Rüddel, C. Fleischmann, C. Haas, U. Dennler, K. Reinhart P059 - “Zero CLABSI” – can we get there? Obstacles on the 4 year journey and our strategies to overcome them – experience from an Indian ICU V. Adora, A. Kar, A. Chakraborty, S. Roy, A. Bandyopadhyay, M. Das P060 - Novel molecular techniques to identify central venous catheter (CVC) associated blood stream infections (BSIs) T. Mann Ben Yehudah, G. Ben Yehudah, M. Salim, N. Kumar, L. Arabi, T. Burger, P. Lephart, E. Toth-martin P061 - Zero clabsi” – can we get there? Obstacles on the 4 year journey and our strategies to overcome them – experience from an Indian ICU R. Rao, A. Kar, A. Chakraborty P062 - Prevention of central line-associated bloodstream infections in intensive care units: An international online survey C. Valencia, N. Hammami, S. Blot, J. L. Vincent, M. L. Lambert P063 - 30 days antimicrobial efficacy of non-leaching central venous catheters J. Brunke, T. Riemann, I. Roschke P064 - Efficacy of noble metal alloy-coated catheter in prevention of bacteriuria R. Tincu, C. Cobilinschi, D. Tomescu, Z. Ghiorghiu, R. Macovei P065 - Predicting bacteremic urinary tract infection in community setting: A prospective observational study S. Nimitvilai, K. Jintanapramote, S. Jarupongprapa P066 - Eight-year analysis of acinetobacter spp. monobacteremia in surgical and medical intensive care units at university hospital in Lithuania D. Adukauskiene, D. Valanciene P067 - Group A and group B streptococcal infections in intensive care unit – our experience in a tertiary centre G. Bose, V. Lostarakos, B. Carr P068 - Improved detection of spontaneous bacterial peritonitis by uritop + tm strip test and inoculation of blood culture bottles with ascitic fluid S. Khedher, A. Maaoui, A. Ezzamouri, M. Salem P069 - Increased risk of cellulitis in patients with congestive heart failure: a population based cohort study J. Chen P070 - Outcomes of severe cellulitis and necrotizing fasciitis in the critically ill D. R. Cranendonk, L. A. Van Vught, M. A. Wiewel, O. L. Cremer, J. Horn, M. J. Bonten, M. J. Schultz, T. Van der Poll, W. J. Wiersinga P071 - Botulism outbreak associated with people who inject drugs (PWIDs) in Scotland. M. Day, G. Penrice, K. Roy, P. Robertson, G. Godbole, B. Jones, M. Booth, L. Donaldson P072 - Surveillance of ESBL-producing enterobacteriaceae fecal carriers in the ICU Y. Kawano, H. Ishikura P073 - Prevalence of ESBL and carbapenemase producing uropathogens in a newly opened hospital in south India S. Sreevidya, N. Brahmananda Reddy, P. Muraray Govind, R. Pratheema, J. Devachandran Apollo Speciality Hospital - OMR, Chennai, India P074 - Prevalence, risk factors and outcomes of methicillin-resistant staphylococcus aureus nasal colonization in critically ill patients H. Al-Dorzi, M. Almutairi, B. Alhamadi, A. Crizaldo Toledo, R. Khan, B. Al Raiy, Y. Arabi P075 - Multidrug-resistant Acinetobacter baumannii infection in intensive care unit patients in a hospital with building construction: Is there an association? H. Talaie P076 - Multidrug-resistant organisms in a Dutch ICU J. A. Van Oers, A. Harts, E. Nieuwkoop, P. Vos P077 - Epidemiology and risk factors of ICU acquired infections caused by multidrug-resistant gram negative bacilli Y. Boussarsar, F. Boutouta, S. Kamoun, I. Mezghani, S. Koubaji, A. Ben Souissi, A. Riahi, M. S. Mebazaa P078 - Improving outcomes of severe infections by multidrug-resistant pathogens with polyclonal IgM-enriched immunoglobulins E. Giamarellos-Bourboulis, N. Tziolos, C. Routsi, C. Katsenos, I. Tsangaris, I. Pneumatikos, G. Vlachogiannis, V. Theodorou, A. Prekates, E. Antypa, V. Koulouras, N. Kapravelos, C. Gogos, E. Antoniadou, K. Mandragos, A. Armaganidis P079 - Must change the medical practice in ICU? A. R. Robles Caballero, B. Civantos, J. C. Figueira, J. López P080 - Mediterranean spotted fever in an infectious diseases intensive care unit A. Silva-Pinto, F. Ceia, A. Sarmento, L. Santos P081 - Clinical features and outcomes of patients with Middle East respiratory syndrome requiring admission to a saudi intensive care unit: A retrospective analysis of 31 cases G. Almekhlafi, Y. Sakr P082 - The ICU response to a hospital outbreak of Middle East respiratory syndrome coronavirus infection H. Al-Dorzi, R. Khan, S. Baharoon, A. Aldawood, A. Matroud, J. Alchin, S. Al Johani, H. Balkhy, Y. Arabi P083 - Middle East respiratory syndrome: Surveillance data analysis S. Alsolamy, S. Y. Yousif, B. O. Alotabi, A. S. Alsaawi P085 - Use of Taqman array card molecular diagnostics in severe pneumonia: A case series J. Ang, MD Curran, D. Enoch, V. Navapurkar, A. Conway Morris P086 - ‘BUNS’: An investigation protocol improves the ICU management of pneumonia R. Sharvill, J. Astin P087 - Pneumonia in patients following secondary peritonitis: epidemiological features and impact on mortality M. Heredia-Rodríguez, E. Gómez-Sánchez, M. T. Peláez-Jareño, E. Gómez-Pesquera, M. Lorenzo-López, P. Liu-Zhu, M. Aragón-Camino, A. Hernández-Lozano, A. Sánchez-López, E. Álvarez-Fuente, E. Tamayo P088 - The use of the “CURB-65 score” by emergency room clinicians in a large teaching hospital J. Patel, C. Kruger P089 - Incidence of community acquired pneumonia with viral infection in mechanically ventilated patients in the medical intensive care unit J. O’Neal, H. Rhodes, J. Jancik P090 - The SAATELLITE Study: Prevention of S aureus Nosocomial Pneumonia (NP) with MEDI4893, a Human Monoclonal Antibody (mAb) Against S aureus B. François, P. F. Laterre, P. Eggimann, A. Torres, M. Sánchez, P. F. Dequin, G. L. Bassi, J. Chastre, H. S. Jafri P091 - Risk factors and microbiological profile for nosocomial infections in trauma patients M. Ben Romdhane, Z. Douira, S. Kamoun, M. Bousselmi, A. Ben Souissi, Y. Boussarsar, A. Riahi, M.S. Mebazaa P092 - Correlation between percentages of ventilated patients developed vap and use of antimicrobial agents in ICU patients. A. Vakalos, V. Avramidis P093 - A comparison of two ventilator associated pneumonia surveillance techniques T. H. Craven, G. Wojcik, K. Kefala, J. McCoubrey, J. Reilly, R. Paterson, D. Inverarity, I. Laurenson, T. S. Walsh P094 - Lung ultrasound before and after fiberbronchoscopy - modifications may improve ventilator-associated pneumonia diagnosis S. Mongodi, B. Bouhemad, A. Orlando, A. Stella, G. Via, G. Iotti, A. Braschi, F. Mojoli P095 - Comparing the accuracy of predictors of mortality in ventilator-associated pneumonia M. Haliloglu, B. Bilgili, U. Kasapoglu, I. Sayan, M. Süzer Aslan, A. Yalcın, I. Cinel P096 - Impact of pRBCs transfusion on percentage of ventilated patients developed VAP in ICU patients A. Vakalos, V. Avramidis P097 - The impact of a series of interventions on the rate of ventilator associated pneumonia in a large teaching hospital H. E. Ellis, K. Bauchmuller, D. Miller, A Temple P098 - The EVADE study: Prevention of Nosocomial Pneumonia (NP) caused by P aeruginosa with MEDI3902, a Novel Bispecific Monoclonal Antibody, against P aeruginosa virulence factors J. Chastre, B. François, A. Torres, C. E. Luyt, M. Sánchez, M. Singer, H. S. Jafri P099 - Short-term inhaled colistin adjunctive therapy for ventilator-associated pneumonia Y. Nassar, M. S. Ayad P100 - Effect of aerosolised colistin on weaning from mechanical ventilation A. Trifi, S. Abdellatif, F. Daly, R. Nasri, S. Ben Lakhal P101 - Septic shock is an independent risk factor for colistin-induced severe acute kidney injury: a retrospective cohort study B. Bilgili, M. Haliloglu, F. Gul, I. Cinel P102 - Nosocomial pneumonia - emphasis on inhaled tobramycin A. Kuzovlev, A. Shabanov, S. Polovnikov, V. Moroz P103 - In vitro evaluation of amikacin inhale and commercial nebulizers in a mechanical ventilator N. Kadrichu, T. Dang, K. Corkery, P. Challoner P104 - The effects of nebulized amikacin/fosfomycin and systemic meropenem on severe amikacin-resistant meropenem-susceptible P.aeruginosa pneumonia G. Li Bassi, E. Aguilera, C. Chiurazzi, C. Travierso, A. Motos, L. Fernandez, R. Amaro, T. Senussi, F. Idone, J. Bobi, M. Rigol, A. Torres P105 - Optimization of gentamicin peak concentrations in critically ill patients C. J. Hodiamont, N. P. Juffermans, J. M. Janssen, C. S. Bouman, R. A. Mathôt, M. D. De Jong, R. M. Van Hest P106 - Systematic review of cefepime induced neurotoxicity L. Payne, G. L. Fraser P107 - Unasyn® causes QT prolongation during treatment of intensive care patients B. Tudor, M. Lahner, G. Roth, C. Krenn P108 - Comparative study between teicoplanin and vancomycin in methicillin-resistant staphylococcus aureus (mrsa) infectious of toxicological intensive care unit (ticu) patients – Tehran, Iran H. Talaie P109 - Phage therapy against antimicrobial resistance, design of the first clinical study phagoburn P. Jault, J. Gabard, T. Leclerc, S. Jennes, Y. Que, A. Rousseau, F. Ravat P110 - Antibiotic dosing errors in critically ill patients with severe sepsis or septic shock H. Al-Dorzi, A. Eissa, S. Al-Harbi, T. Aldabbagh, R. Khan, Y. Arabi P111 - Does empiric antifungal therapy improve survival in septic critically ill patients? (immunocompromised excluded) A. Trifi, S. Abdellatif, F. Daly, R. Nasri, S. Ben Lakhal P112 - Neurocysticercosis-Qatar experience F. Paramba, N. Purayil, V. Naushad, O. Mohammad, V. Negi, P. Chandra P113 - Early indicators in acute haemorrhagic shock A. Kleinsasser P114 - Filtering of red blood cells reduces the inflammatory response of pulmonary cells in an in vitro model of mechanical ventilation M. R. Witrz, J. F. Buchner-Doeven, A. M. Tuip-de Boer, J. C. Goslings, N. P. Juffermans P115 - Microparticles from red blood cell transfusion induce a pro-coagulant and pro-inflammatory endothelial cell response M. Van Hezel, M. Straat, A Boing, R Van Bruggen, N Juffermans P116 - The contribution of cytokines on thrombosis development during hospitalization in ICU D. Markopoulou, K. Venetsanou, V. Kaldis, D. Koutete, D. Chroni, I. Alamanos P117 - Prophylactic enoxaparin dosing and adjustment through anti-xa monitoring in an inpatient burn unit L. Koch, J. Jancik, H. Rhodes, E. Walter P118 - Determination of optimal cut-off values of haemoglobin, platelet count and fibrinogen at 24 hours after injury associated with mortality in trauma patients K. Maekawa, M. Hayakawa, S. Kushimoto, A. Shiraishi, H. Kato, J. Sasaki, H. Ogura, T. Matauoka, T. Uejima, N. Morimura, H. Ishikura, A. Hagiwara, M. Takeda P119 - Trauma-induced coagulopathy - prothrombin complex concentrate vs fresh frozen plasma O. Tarabrin, S. Shcherbakow, D. Gavrychenko, G. Mazurenko, V. Ivanova, O. Chystikov P120 - First study to prove the superiority of prothrombin complex concentrates on mortality rate over fresh frozen plasma in patients with acute bleeding C. Plourde, J. Lessard, J. Chauny, R. Daoust P121 - Prothrombin complex concentrate vs fresh frozen plasma in obstetric massive bleeding S. Shcherbakow, O. Tarabrin, D. Gavrychenko, G. Mazurenko, O. Chystikov P122 - Impact of FFP transfusion on VAP in ICU patients A. Vakalos, V. Avramidis P123 - Preoperative platelet function test and the thrombin generation assay are predictive for blood loss after cardiac surgery L. Kropman, L. In het Panhuis, J. Konings, D. Huskens, E. Schurgers, M. Roest, B. De Laat, M. Lance P124 - Rotational thromboelastometry versus standard coagulation tests before surgical interventions M. Durila, P. Lukas, M. Astraverkhava, J. Jonas P125 - Correction of impaired clot quality and stability by fibrinogen and activated prothrombin complex concentrate in a model of severe thrombocytopenia I. Budnik, B. Shenkman P126 - Assessment of point-of-care prothrombin time analyzer as a monitor after cardiopulmonary bypass H. Hayami, Y. Koide, T. Goto P127 - Disseminated intravascular coagulation (dic) is underdiagnosed in critically ill patients: do we need d-dimer measurements? R. Iqbal, Y. Alhamdi, N. Venugopal, S. Abrams, C. Downey, C. H. Toh, I. D. Welters P128 - Validity of the age-adjusted d-dimer cutoff in patients with COPD B. Bombay, J. M. Chauny, R. D. Daoust, J. L. Lessard, M. M. Marquis, J. P. Paquet P129 - A scoping review of strategies for prevention and management of bleeding following paediatric cardiopulmonary bypass surgery K. Siemens, D. Sangaran, B. J. Hunt, A. Durward, A. Nyman, I. A. Murdoch, S. M. Tibby P130 - Nadir hemoglobulin during cardiopulmonary bypass: impact on postoperative morbidity and mortality F. Ampatzidou, D. Moisidou, E. Dalampini, M. Nastou, E. Vasilarou, V. Kalaizi, H. Chatzikostenoglou, G. Drossos P131 - Red blood cell transfusion do not influence the prognostic value of RDW in critically ill patients S. Spadaro, A. Fogagnolo, T. Fiore, A. Schiavi, V. Fontana, F. Taccone, C. Volta P132 - Reasons for admission in the paediatric intensive care unit and the need for blood and blood products transfusions E. Chochliourou, E. Volakli, A. Violaki, E. Samkinidou, G. Evlavis, V. Panagiotidou, M. Sdougka P133 - The implementation of a massive haemorrhage protocol (mhp) for the management of major trauma: a ten year, single-centre study R. Mothukuri, C. Battle, K. Guy, G. Mills, P. Evans P134 - An integrated major haemorrhage protocol for pre-hospital and retrieval medical teams J. Wijesuriya, S. Keogh P135 - The impact of transfusion thresholds on mortality and cardiovascular events in patients with cardiovascular disease (non-cardiac surgery): a systematic review and meta-analysis A. Docherty, R. O’Donnell, S. Brunskill, M. Trivella, C. Doree, L. Holst, M. Parker, M. Gregersen, J. Almeida, T. Walsh, S. Stanworth P136 - The relationship between poor pre-operative immune status and outcome from cardiac surgery is specific to the peri-operative antigenic threat S. Moravcova, J. Mansell, A. Rogers, R. A. Smith, C. Hamilton-Davies P137 - Impact of simple clinical practice guidelines for reducing post-operative atrial fibrillation after cardiac surgery. A. Omar, M. Allam, O. Bilala, A. Kindawi, H. Ewila P138 - Dexamethasone administration during cardiopulmonary bypass has no beneficial effects on elective postoperative cardiac surgery patients F. Ampatzidou, D. Moisidou, M. Nastou, E. Dalampini, A. Malamas, E. Vasilarou, G. Drossos P139 - Intra-aortic balloon counterpulsation in patients undergoing cardiac surgery (IABCS): preliminary results G. Ferreira, J. Caldas, J. Fukushima, E. A. Osawa, E. Arita, L. Camara, S. Zeferino, J. Jardim, F. Gaioto, L. Dallan, F. B. Jatene, R. Kalil Filho, .F Galas, L. A. Hajjar P140 - Effects of low-dose atrial natriuretic peptide infusion on cardiac surgery-associated acute kidney injury C. Mitaka, T. Ohnuma, T. Murayama, F. Kunimoto, M. Nagashima, T. Takei, M. Tomita P141 - Acute kidney injury influence on high sensitive troponin measurements after cardiac surgery A. Omar, K. Mahmoud, S. Hanoura, S. Sudarsanan, P. Sivadasan, H. Othamn, Y. Shouman, R. Singh, A. Al Khulaifi P142 - Complex evaluation of endothelial dysfunction markers for prognosis of outcomes in patients undergoing cardiac surgery I. Mandel, S. Mikheev, I. Suhodolo, V. Kiselev, Y. Svirko, Y. Podoksenov P143 - New-onset atrial fibrillation in intensive care: incidence, management and outcome S. A. Jenkins, R. Griffin P144 - One single spot measurement of the sublingual microcirculation during acute pulmonary hypertension in a pig model of shock M. S. Tovar Doncel, A. Lima, C. Aldecoa, C. Ince P145 - Assessment of levosimendan as a therapeutic option to recruit the microcirculation in cardiogenic shock – initial experience in cardiac ICU A. Taha, A. Shafie, M. Mostafa, N. Syed, H. Hon P146 - Terlipressin vs. norepinephrine in the Potential Multiorgan Donor(PMD) F. Righetti, E. Colombaroli, G. Castellano P147 - Echocardiography in the potential heart donor exposed to substitution hormonotherapy F. Righetti, E. Colombaroli P148 - Machine learning can reduce rate of monitor alarms M. Hravnak, L. C. Chen, A. D. Dubrawski, G. C. Clermont, M. R. Pinsky P149 - Peripherally inserted central catheters placed in the ICU S. Gonzalez, D. Macias, J. Acosta, P. Jimenez, A. Loza, A. Lesmes, F. Lucena, C. Leon P150 - Recordings of abnormal central venous pressure waveform morphology during an episode of pulmonary hypertension in a porcine shock model M. S. Tovar Doncel, C. Ince, C. Aldecoa, A. Lima P151 - Ultrasound guided central venous access technique among French intensivists M. Bastide, J. Richecoeur, E. Frenoy, C. Lemaire, B. Sauneuf, F. Tamion, S. Nseir, D. Du Cheyron, H. Dupont, J. Maizel P152 - Predictive ability of the Pv-aCO2 gap in patients with shock M. Shaban, R. Kolko, N. Salahuddin, M. Sharshir, M. AbuRageila, A. AlHussain P153 - Comparison of echocardiography and pulmonary artery catheter measurements of hemodynamic parameters in critical ill patients P. Mercado, J. Maizel, L. Kontar, D. Titeca, F. Brazier, A. Riviere, M. Joris, T. Soupison, B. De Cagny, M. Slama P154 - The volume clamp method for noninvasive cardiac output measurement in postoperative cardiothoracic surgery patients: a comparison with intermittent pulmonary artery thermodilution J. Wagner, A. Körner, M. Kubik, S. Kluge, D. Reuter, B. Saugel P155 - Hemodynamic monitoring in patients with septic shock (SS) – CPCCO (continuous pulse contour cardiac output) vs. TEE (transesophageal echocardiography) E. Colombaroli, F. Righetti, G. Castellano P156 - Cardiac output measurement with transthoracic echocardiography in critically ill patients: a pragmatic clinical study T. Tran, D. De Bels, A. Cudia, M. Strachinaru, P. Ghottignies, J. Devriendt, C. Pierrakos P157 - Left ventricular outflow tract velocity time integral correlates with stroke volume index in mechanically ventilated patients Ó. Martínez González, R. Blancas, J. Luján, D. Ballesteros, C. Martínez Díaz, A. Núñez, C. Martín Parra, B. López Matamala, M. Alonso Fernández, M. Chana P158 - Transpulmonary thermodilution (TPTD) derived from femoral vs. jugular central venous catheter: validation of a previously published correction formula and a proprietary correction formula for global end-diastolic volume index (GEDVI) W. Huber, M. Eckmann, F. Elkmann, A. Gruber, I. Klein, R. M. Schmid, T. Lahmer P160 - Dynamic arterial elastance calculated with lidcoplus monitor does not predict changes in arterial pressure after a fluid challenge in postsurgical patients D. Bastoni, H. Aya, L. Toscani, L. Pigozzi, A. Rhodes, M. Cecconi P159 - Venous return driving pressure and resistance in acute blood volume changes P. W. Moller, S. Sondergaard, S. M. Jakob, J. Takala, D. Berger P160 - Dynamic arterial elastance calculated with lidcoplus monitor does not predict changes in arterial pressure after a fluid challenge in postsurgical patients D. Bastoni, H. Aya, L. Toscani, L. Pigozzi, A. Rhodes, M. Cecconi P161 - Analysis of duration of post-operative goal-directed therapy protocol C. Ostrowska, H. Aya, A. Abbas, J. Mellinghoff, C. Ryan, D. Dawson, A. Rhodes, M. Cecconi P162 - Hemodynamic optimization – back to square one? M. Cronhjort, O. Wall, E. Nyberg, R. Zeng, C. Svensen, J. Mårtensson, E. Joelsson-Alm P163 - Effectiveness of fluid thoracic content measurement by bioimpedance guiding intravascular volume optimization in patients with septic shock M. Aguilar Arzapalo, L. Barradas, V. Lopez, M. Cetina P164 - A systematic review on the role of internal jugular vein ultrasound measurements in assessment of volume status in critical shock patients N. Parenti, C. Palazzi, L. A. Amidei, F. B. Borrelli, S. C. Campanale, F. T. Tagliazucchi, G. S. Sedoni, D. L. Lucchesi, E. C. Carella, A. L Luciani P165 - Importance of recognizing dehydration in medical Intensive Care Unit M. Mackovic, N. Maric, M. Bakula P166 - Effect of volume for a fluid challenge in septic patients H. Aya, A. Rhodes, R. M. Grounds, N. Fletcher, M. Cecconi P167 - Fluid bolus practices in a large Australian intensive care unit B. Avard, P. Zhang P168 - Liberal late fluid management is associated with longer ventilation duration and worst outcome in severe trauma patients: a retrospective cohort of 294 patients M. Mezidi, J. Charbit, M. Ould-Chikh, P. Deras, C. Maury, O. Martinez, X. Capdevila P169 - Association of fluids and outcomes in emergency department patients hospitalized with community-acquired pneumonia P. Hou, W. Z. Linde-Zwirble, I. D. Douglas, N. S. Shapiro P170 - Association of positive fluid balance with poor outcome in medicosurgical ICU patients A. Ben Souissi, I. Mezghani, Y. Ben Aicha, S. Kamoun, B. Laribi, B. Jeribi, A. Riahi, M. S. Mebazaa P171 - Impact of fluid balance to organ dysfunction in critically ill patients C. Pereira, R. Marinho, R. Antunes, A. Marinho P172 - Volume bolus in ICU patients: do we need to balance our crystalloids? M. Crivits, M. Raes, J. Decruyenaere, E. Hoste P173 - The use of 6 % HES solution do not reduce total fluid requirement in the therapy of patients with burn shock V. Bagin, V. Rudnov, A. Savitsky, M. Astafyeva, I. Korobko, V. Vein P174 - Electron microscopic assessment of acute kidney injury in septic sheep resuscitated with crystalloids or different colloids T. Kampmeier , P. Arnemann, M. Hessler, A. Wald, K. Bockbreder, A. Morelli, H. Van Aken, S. Rehberg, C. Ertmer P175 - Alterations of conjunctival microcirculation in a sheep model of haemorrhagic shock and resuscitation with 0.9 % saline or balanced tetrastarch P. Arnemann, M. Hessler, T. Kampmeier, S. Rehberg, H. Van Aken, C. Ince, C. Ertmer P176 - A single centre nested pilot study investigating the effect of using 0.9 % saline or Plasma-Lyte 148 ® as crystalloid fluid therapy on gastrointestinal feeding intolerance in mechanically ventilated patients receiving nasogastric enteral nutrition S. Reddy, M. Bailey, R. Beasley, R. Bellomo, D. Mackle, A. Psirides, P. Young P177 - A single centre nested pilot study investigating the effect on post-operative bleeding of using 0.9 % saline or Plasma-Lyte® 148 as crystalloid fluid therapy in adults in ICU after heart surgery S. Reddy, M. Bailey, R. Beasley, R. Bellomo, D. Mackle, P. Young P178 - Extreme hypernatremia and sepsis in a patient with Huntington’s dementia: a conundrum in fluid management H. Venkatesh, S. Ramachandran, A. Basu, H. Nair P179 - Diagnosis and management of severe hypernatraemia in the critical care setting S. Egan, J. Bates P180 - Correlation between arterial blood gas and electrolyte disturbances during hospitalization and outcome in critically ill patients S. Oliveira, N. R. Rangel Neto, F. Q. Reis P181 - Missing the “I” in MUDPILES – a rare cause of high anion gap metabolic acidosis (HAGMA) C. P. Lee, X. L. Lin, C. Choong , K. M. Eu, W. Y. Sim , K. S. Tee, J. Pau , J. Abisheganaden P182 - Plasma NGAL and urinary output: potential parameters for early initiation of renal replacement therapy K. Maas, H. De Geus P183 - Renal replacement therapy for critically ill patients: an intermittent continuity E. Lafuente, R. Marinho, J. Moura, R. Antunes, A. Marinho P184 - A survey of practices related to renal replacement therapy in critically ill patients in the north of England. T. E. Doris, D. Monkhouse, T. Shipley, S. Kardasz, I Gonzalez P185 - High initiation creatinine associated with lower 28-day mortality in critically ill patients necessitating continuous renal replacement therapy S. Stads, A. J. Groeneveld P186 - The impact of Karnofsky performance scale on outcomes in acute kidney injury patients receiving renal replacement therapy on the intensive care unit I. Elsayed, N. Ward, A. Tridente, A. Raithatha P187 - Severe hypophosphatemia during citrate-anticoagulated CRRT A. Steuber, C. Pelletier, S. Schroeder, E. Michael, T. Slowinski, D. Kindgen-Milles P188 - Citrate regional anticoagulation for post dilution continuous renal replacement therapy S. Ghabina P189 - Citrate 18 mmol/l improves anticoagulation during RRT with adsorbing filters F. Turani, A. Belli, S. Busatti, G. Barettin, F. Candidi, F. Gargano, R. Barchetta, M. Falco P190 - Calcium gluconate instead of calcium chloride in citrate-anticoagulated CVVHD O. Demirkiran, M. Kosuk, S. Bozbay P191 - Enhanced clearance of interleukin-6 with continuous veno-venous haemodialysis (CVVHD) using Ultraflux EMiC2 vs. Ultraflux AV1000S V. Weber, J. Hartmann, S. Harm, I. Linsberger, T. Eichhorn, G. Valicek, G. Miestinger, C. Hoermann P192 - Removal of bilirubin with a new adsorbent system: in vitro kinetics S. Faenza, D. Ricci, E. Mancini, C. Gemelli, A. Cuoghi, S. Magnani, M. Atti P193 - Case series of patients with severe sepsis and septic shock treated with a new extracorporeal sorbent T. Laddomada, A. Doronzio, B. Balicco P194 - In vitro adsorption of a broad spectrum of inflammatory mediators with CytoSorb® hemoadsorbent polymer beads M. C. Gruda, P. O’Sullivan, V. P. Dan, T. Guliashvili, A. Scheirer, T. D. Golobish, V. J. Capponi, P. P. Chan P195 - Observations in early vs. late use of cytosorb therapy in critically ill patients K. Kogelmann, M. Drüner, D. Jarczak P196 - Oxiris membrane decreases endotoxin during rrt in septic patients with basal EAA > 0,6 F. Turani, A. B. Belli, S. M. Martni, V. C. Cotticelli, F. Mounajergi, R. Barchetta P197 - An observational prospective study on the onset of augmented renal clearance: the first report S. Morimoto, H. Ishikura P198 - An ultrasound- guided algorithm for the management of oliguria in severe sepsis I. Hussain, N. Salahuddin, A. Nadeem, K. Ghorab, K. Maghrabi P199 - Ultrasound in acute kidney injury (aki). First findings of farius, an education-programme in structural ultrasonography S. K. Kloesel, C. Goldfuss, A. Stieglitz, A. S. Stieglitz, L. Krstevska, G. Albuszies P200 - Effectiveness of renal angina index score predicting acute kidney injury on critically ill patients M. Aguilar Arzapalo, L. Barradas, V. Lopez, A. Escalante, G. Jimmy, M. Cetina P201 - Time length below blood pressure thresholds and progression of acute kidney injury in critically ill patients with or without sepsis: a retrospective, exploratory cohort study J. Izawa, T. Iwami, S. Uchino, M. Takinami, T. Kitamura, T. Kawamura P202 - Anaemia does not affect renal recovery in acute kidney injury J. G. Powell-Tuck, S. Crichton, M. Raimundo, L. Camporota, D. Wyncoll, M. Ostermann P203 - Estimated glomerular filtration rate based on serum creatinine: actual practice in Dutch ICU’s A. Hana, H. R. De Geus P204 - Comparison of estimated glomerular filtration rate calculated by mdrd, ckd-epi-serum-creatinine and ckd-epi-cystatin-c in adult critically ill patients H. R. De Geus, A. Hana P205 - Early diagnosis of septic acute kidney injury in medical critical care patients with a urine cell cycle arrest marker: insulin like growth factor binding protein-7 (IGFBP-7) M. Aydogdu, N. Boyaci, S. Yuksel, G. Gursel, A. B. Cayci Sivri P206 - Urinary neutrophil gelatinase-associated lipocalin as early biomarker of severe acute kidney injury in intensive care J. Meza-Márquez, J. Nava-López, R. Carrillo-Esper P207 - Shrunken pore syndrome is associated with a sharp rise in mortality in patients undergoing elective coronary artery bypass grafting A. Dardashti, A. Grubb P208 - The biomarker nephrocheck™ can discriminate the septic shock patients with an akin 1 or 2 acute renal failure who will not progress toward the akin 3 level J. Maizel, M. Wetzstein, D. Titeca, L. Kontar, F. Brazier, B. De Cagny, A. Riviere, T. Soupison, M. Joris, M. Slama P209 - A worldwide multicentre evaluation of acute kidney injury in septic and non-septic critically ill patients: the intensive care over nations (icon) audit E. Peters, H. Njimi, P. Pickkers, J. L. Vincent P210 - Does enhanced recovery after surgery reduce the incidence of acute kidney injury in those undergoing major gynae-oncological surgery? M. Waraich , J. Doyle, T. Samuels, L. Forni P211 - Identification of risk factors for the development of acute kidney injury after lower limb arthroplasty N. Desai, R. Baumber, P. Gunning, A. Sell P212 - Incidences and associations of acute kidney injury after major trauma S. Lin, H. Torrence, M. O’Dwyer, C. Kirwan, J. Prowle P213 - Acute kidney injury of major trauma patients T Kim P214 - Trajectory of serum creatinine after major surgery and the diagnosis of acute kidney injury M. E. O’Connor, R. W. Hewson, C. J. Kirwan, R. M. Pearse, J. Prowle P215 - Epidemiology of acute kidney injury after cardiac surgery. 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Bhandari P221 - Setting optimal flow rate during high flow nasal cannula support: preliminary results T. Mauri, C. Turrini, T. Langer, P. Taccone, C. A. Volta, C. Marenghi, L. Gattinoni, A. Pesenti P222 - Dose to dose consistency across two different gas flow rates using cystic fibrosis and normal adult breathing profiles during nasal high flow oxygen therapy L. Sweeney, A . O’ Sullivan, P. Kelly, E. Mukeria, R. MacLoughlin P223 - Final results of an evaluation of airway medix closed suction system compared to a standard closed suction system M. Pfeffer, J. T. Thomas, G. B. Bregman, G. K. Karp, E. K. Kishinevsky, D. S. Stavi, N. A. Adi P224 - Different cuff materials and different leak tests - one size does not fit all T. Poropat, R. Knafelj P225 - Observational study on the value of the cuff-leak test and the onset of upper airway obstruction after extubation E. Llopart, M. Batlle, C. De Haro, J. Mesquida, A. Artigas P226 - A device for emergency transtracheal lung ventilation D. Pavlovic, L. Lewerentz, A. Spassov, R. Schneider P227 - Long-term outcome and health-related quality of life in patients discharged from the intensive care unit with a tracheostomy and with or without prolonged mechanical ventilation S. De Smet, S. De Raedt, E. Derom, P Depuydt, S. Oeyen, D. Benoit, J. Decruyenaere P228 - Ultrasound-guided percutaneous dilational tracheostomy versus bronchoscopy-guided percutaneous dilational tracheostomy in critically ill patients (trachus): a randomized clinical trial A. Gobatto, B. Bese, P. Tierno, L. Melro, P. Mendes, F. Cadamuro, M. Park, L. M. Malbouisson P229 - Is it safe to discharge patients with tracheostomy from the ICU to the ward? B. C. Civanto, J. L. Lopez, A. Robles, J. Figueira, S. Yus, A. Garcia P230 - The application of tracheostomy in children in ICU A. Oglinda, G. Ciobanu, C. Oglinda, L. Schirca, T. Sertinean, V. Lupu P231 - The impact of passive humidifiers on aerosol drug delivery during mechanical ventilation P. Kelly, A. O’Sullivan, L. Sweeney, R. MacLoughlin P232 - Evaluation of vibrating mesh and jet nebuliser performance at two different attachment setups in line with a humidifier nebuliser system A. O’Sullivan, P. Kelly, L. Sweeney, E. Mukeria, M. Wolny , R. MacLoughlin P233 - Psv-niv versus cpap in the treatment of acute cardiogenic pulmonary edema A. Pagano, F. Numis, G. Vison, L. Saldamarco, T. Russo, G. Porta, F. Paladino P234 - Noninvasive ventilation in patients with haematologic malignancy: a retrospective review C. Bell, J. Liu, J. Debacker, C. Lee, E. Tamberg, V. Campbell, S. Mehta P235 - Use of non-invasive ventilation in infectious diseases besides classical indications A. Silva-Pinto, A. Sarmento, L. Santos P236 - The impact of fragility on noninvasive mechanical ventilation application and results in the ICU Ý. Kara, F. Yýldýrým, A. Zerman, Z. Güllü, N. Boyacý, B. Basarýk Aydogan, Ü. Gaygýsýz, K. Gönderen, G. Arýk, M. Turkoglu, M. Aydogdu, G. Aygencel, Z. Ülger, G. Gursel P237 - Effects of metabolic alkalosis on noninvasive ventilation success and ICU outcome in patients with hypercapnic respiratory failure N. Boyacý, Z. Isýkdogan, Ö. Özdedeoglu, Z. Güllü, M. Badoglu, U. Gaygýsýz, M. Aydogdu, G. Gursel P238 - Asynchrony index and breathing patterns of acute exacerbation copd patients assisted with noninvasive pressure support ventilation and neurally adjusted ventilatory assist N. Kongpolprom, C. Sittipunt P239 - High frequency jet ventilation for severe acute hypoxemia A. Eden, Y. Kokhanovsky, S. Bursztein – De Myttenaere, R. Pizov P240 - HFOV revisited: a 7 year retrospective analysis of patients receiving HFOV who met oscillate trial entry criteria L. Neilans, N. MacIntyre P241 - Implementation of a goal-directed mechanical ventilation order set driven by respiratory therapists can improve compliance with best practices for mechanical ventilation M. Radosevich, B. Wanta, V. Weber, T. Meyer, N. Smischney, D. Brown, D. Diedrich P242 - A reduction in tidal volumes for ventilated patients on ICU calculated from IBW. can it minimise mortality in comparison to traditional strategies? A . Fuller, P. McLindon, K. Sim P243 - Predictive value of lung aeration scoring using lung ultrasound in weaning failure M. Shoaeir, K. Noeam, A. Mahrous, R. Matsa, A. Ali P244 - Conventional versus automated weaning from mechanical ventilation using SmartCare™ C. Dridi, S. Koubaji, S. Kamoun, F. Haddad, A. Ben Souissi, B. Laribi, A. Riahi, M. S. Mebazaa P245 - Ultrasonographic evaluation protocol for weaning from mechanichal ventilation A. Pérez-Calatayud, R. Carrillo-Esper, A. Zepeda-Mendoza, M. Diaz-Carrillo, E. Arch-Tirado P246 - Diaphragm ultrasonography: a method for weaning patients from mechanical ventilation S. Carbognin, L. Pelacani, F. Zannoni, A. Agnoli, G. Gagliardi P247 - Dorsal diaphragmatic excursion tracks transpulmonary pressure in ventilated ARDS patients: a potential non-invasive indicator of lung recruitment? R. Cho, A. Adams , S. Lunos, S. Ambur, R. Shapiro, M. Prekker P248 - Pulse oximetry in the icu patient: is the perfusion index of any value? M. Thijssen, L. Janssen, N. Foudraine P249 - Ventilation is a better assessment of respiratory status than EtCO2 C. J. Voscopoulos, J. Freeman P250 - Evaluation of the relationship between non-invasive minute ventilation and end-tidal CO2 in patients undergoing general vs spinal anesthesia C. J. Voscopoulos, J. Freeman, E. George P251 - Respiratory volume monitoring provides early warning of respiratory depression and can be used to reduce false alarms in non-intubated patients C. J. Voscopoulos, D. Eversole, J. Freeman, E. George P252 - P/i index: a predictive edi-derived weaning index during nava S. Muttini, R. Bigi, G. Villani, N. Patroniti P253 - Adequacy of ventilation in patients receiving opioids in the post anesthesia care unit: minute ventilation versus respiratory rate G. Williams, C. J. Voscopoulos, J. Freeman, E. George P254 - Comparison of regional and global expiratory time constants measured by electrical impedance tomography (EIT) A. Waldmann, S. Böhm, W. Windisch, S. Strassmann, C. Karagiannidis P255 - Electrical impedance tomography: robustness of a new pixel wise regional expiratory time constant calculation A. Waldmann, S. Böhm, W. Windisch, S. Strassmann, C. Karagiannidis P256 - Validation of regional and global expiratory time constant measurement by electrical impedance tomography in ards and obstructive pulmonary diseases C. K. Karagiannidis, A. W. Waldmann, S. B. Böhm, S. Strassmann, W. W. Windisch P257 - Transpulmonary pressure in a model with elastic recoiling lung and expanding chest wall P. Persson, S. Lundin, O. Stenqvist P258 - Lactate in pleural and abdominal effusion G. Porta, F. Numis, C. S. Serra, A. P. Pagano, M. M. Masarone, L. R. Rinaldi, A. A. Amelia, M. F. Fascione, L. A. Adinolfi, E. R. Ruggiero P259 - Outcome of patients admitted to the intensive care with pulmonary fibrosis F. Asota, K. O’Rourke, S. Ranjan, P. Morgan P260 - Sedation and analgesia practice in extra-corporeal membrane oxygenation (ECMO)-treated patients with acute respiratory distress syndrome (ARDS): a retrospective study J. W. DeBacker, E. Tamberg, L. O’Neill, L. Munshi, L. Burry, E. Fan, S. Mehta P261 - Characteristics and outcomes of patients deemed not eligible when referred for veno-venous extracorporeal membrane oxygenation (vv-ECMO) S. Poo, K. Mahendran, J. Fowles, C. Gerrard, A. Vuylsteke P262 - The SAVE SMR for veno-arterial ECMO R. Loveridge, C. Chaddock, S. Patel, V. Kakar, C. Willars, T. Hurst, C. Park, T. Best, A. Vercueil, G. Auzinger P263 - A simplified score to predict early (48 h) mortality in patients being considered for VA-ECMO A. Borgman, A. G. Proudfoot, E. Grins, K. E. Emiley, J. Schuitema, S. J. Fitch, G. Marco, J. Sturgill, M. G. Dickinson, M. Strueber, A. Khaghani, P. Wilton, S. M. Jovinge P264 - Lung function six months post extra corporeal membrane oxygenation (ECMO) for severe acute respiratory failure in adult survivors C. Sampson, S. Harris-Fox P265 - Bicarbonate dialysis removes carbon dioxide in hypoventilated rodents. M. E. Cove, L. H. Vu, A. Sen, W. J. Federspiel, J. A. Kellum P266 - Procalcitonin as predictor of primary graft dysfunction and mortality in post-lung transplantation C. Mazo Torre, J. Riera, S. Ramirez, B. Borgatta, L. Lagunes, J. Rello P267 - New molecular biomarkers of acute respiratory distress syndrome in abdominal sepsis A. K. Kuzovlev, V. Moroz, A. Goloubev, S. Polovnikov, S. Nenchuk P268 - Tight junction’s proteins claudin -5 and regulation by tnf in experimental murine lung injury model of ali/ards V. Karavana, C. Glynos, A. Asimakos, K. Pappas, C. Vrettou, M. Magkou, E. Ischaki, G. Stathopoulos, S. Zakynthinos P269 - Cell counts in endobronchial aspirate to assess airway inflammation in ARDS patients: a pilot study S. Spadaro, I. Kozhevnikova, F. Dalla Corte, S. Grasso, P. Casolari, G. Caramori, C. Volta P270 - Epidemiological and clinical profile of patients with acute respiratory distress syndrome in the surgical intensive care unit surgical, hospital JRA, Antananarivo T. Andrianjafiarinoa, T. Randriamandrato, T. Rajaonera P271 - Effect of high PEEP after recruitment maneuver on right ventricular function in ARDS. Is it good for the lung and for the heart? S. El-Dash, ELV Costa, MR Tucci, F Leleu, L Kontar, B. De Cagny, F. Brazier, D. Titeca, G. Bacari-Risal, J. Maizel, M. Amato, M. Slama P272 - Effect of recruitment maneuver on left ventricular systolic strain P. Mercado, J. Maizel, L. Kontar, D. Titeca, F. Brazier, A. Riviere, M. Joris, T. Soupison, B. De Cagny, S. El Dash, M. Slama P273 - Inhaled nitric oxide – is switching supplier cost effective? Remmington, A. Fischer, S. Squire, M. Boichat P274 - Epidemiological study of severe acute pancreatitis in Japan, comparison of the etiology and the patient outcomes on 1159 patients. H. Honzawa, H. Yasuda, T. Adati, S. Suzaki, M. Horibe, M. Sasaki, M. Sanui P275 - Extracorporeal liver support therapy. Experience in an intensive care unit R. Marinho, J. Daniel, H. Miranda, A. Marinho P276 - Accuracy of mortality prediction models in acute versus acute-on-chronic liver failure in the intensive care setting K. Milinis, M. Cooper, G. R. Williams, E. McCarron, S. Simants, I. Patanwala, I. Welters P277 - Risk of coronary artery disease in patients with chronic liver disease: a population based cohort study Y. Su P278 - 20 years of liver transplantation in Santiago de Compostela (Spain). Experience review J. Fernández Villanueva, R. Fernández Garda, A. López Lago, E. Rodríguez Ruíz, R. Hernández Vaquero, S. Tomé Martínez de Rituerto, E. Varo Pérez P279 - Diarrhea is a risk factor for liver injury and may lead to intestinal failure associated liver disease in critical illness N. Lefel, F. Schaap, D. Bergmans, S. Olde Damink, M. Van de Poll P280 - Bowel care on the intensive care unit: constipation guideline compliance and complications K. Tizard, C. Lister, L. Poole P281 - Malnutrition assessed by phase angle determines outcomes in low risk cardiac surgery patients D. Ringaitiene, D. Gineityte, V. Vicka, I. Norkiene, J. Sipylaite P282 - Preoperative fasting times in an irish hospital A. O’Loughlin, V. Maraj, J. Dowling P283 - Costs and final outcome of early x delayed feeding in a private Brazil ICU M. B. Velasco, D. M. Dalcomune, E. B. Dias, S. L. Fernandes P284 - Can ventilator derived energy expenditure measurements replace indirect calorimetry? T. Oshima, S. Graf, C. Heidegger, L. Genton, V. Karsegard, Y. Dupertuis, C. Pichard P285 - Revisiting the refeeding syndrome: results of a systematic review N. Friedli, Z. Stanga, B. Mueller, P. Schuetz P286 - Compliance with the new protocol for parenteral nutrition in our ICU L. Vandersteen, B. Stessel, S. Evers, A. Van Assche, L. Jamaer, J. Dubois P287 - Nutrition may be another treatment in the intensive care unit where less is more? R. Marinho, H. Castro, J. Moura, J. Valente, P. Martins, P. Casteloes, C. Magalhaes, S. Cabral, M. Santos, B. Oliveira, A. Salgueiro, A. Marinho P288 - Should we provide more protein to critically ill patients? R. Marinho, M. Santos, E. Lafuente, H. Castro, S. Cabral, J. Moura, P. Martins, B. Oliveira, A. Salgueiro, S. Duarte, S. Castro, M. Melo, P. Casteloes, A. Marinho P289 Protein provision in an adult intensive care unit S. Gray P290 - Prevalence and clinical outcomes of vitamin d deficiency in the medical critically ill patients in Songklanagarind hospital K. Maipang, R. Bhurayanontachai P291 - Vitamin d deficiency strongly predicts adverse medical outcome across different medical inpatient populations: results from a prospective study L. G. Grädel, P. Schütz P292 - Omega-3 fatty acids in patients undergoing cardiac surgery: a systematic review and meta-analysis P. Langlois, W. Manzanares P293 - Can 5-hydroxytriptophan prevent post-traumatic stress disorder in critically ill patients? R. Tincu, C. Cobilinschi, D. Tomescu, Z. Ghiorghiu, R. Macovei P294 - Parenteral selenium in the critically ill: an updated systematic review and meta-analysis W. Manzanares, P. Langlois, M. Lemieux, G. Elke, F. Bloos, K. Reinhart, D. Heyland P295 - Probiotics in the critically ill: an updated systematic review and meta-analysis P. Langlois, M. Lemieux, I. Aramendi, D. Heyland, W. Manzanares P296 - Diabetes with hyperglycemic crisis episodes may be associated with higher risk of pancreatic cancer: a population-based cohort study Y. Su P297 - Incidence of hypoglycemia in an intensive care unit depending on insulin protocol R. Marinho, N. Babo, A. Marinho P298 - Severity of the diseases is two-dimensionally correlated to blood glucose, including blood glucose variability, especially in moderately to severely ill patients with glucose intolerance. M. Hoshino, Y. Haraguchi, S. Kajiwara, T. Mitsuhashi, T. Tsubata, M. Aida P299 - A study of glycemic control by subcutaneous glargine injection transition from continuous regular insulin infusion in critically ill patients T. Rattanapraphat, R. Bhurayanontachai, C. Kongkamol, B. Khwannimit P300 - Glycemic control in Portuguese intensive care unit R. Marinho, M. Santos, H. Castro, E. Lafuente, A. Salgueiro, S. Cabral, P. Martins, J. Moura, B. Oliveira, M. Melo, B. Xavier, J. Valente, C. Magalhaes, P. Casteloes, A. Marinho P301 - Impact of hyperglycemia duration on the day of operation on short-term outcome of cardiac surgery patients D. Moisidou, F. Ampatzidou, C. Koutsogiannidis, M. Moschopoulou, G. Drossos P302 - Lactate levels in diabetic ketoacidosis patients at ICU admissions G. Taskin, M. Çakir, AK Güler, A. Taskin, N. Öcal, S. Özer, L. Yamanel P303 - Intensive care implications of merging heart attack centre units in London J. M. Wong, C. Fitton, S. Anwar, S. Stacey P304 - Special characteristics of in-hospital cardiac arrests M. Aggou, B. Fyntanidou, S. Patsatzakis, E. Oloktsidou, K. Lolakos, E. Papapostolou, V. Grosomanidis P305 - Clinical evaluation of ICU-admitted patients who were resuscitated in the general medicine ward S. Suda , T. Ikeda, S. Ono, T. Ueno, Y. Izutani P306 - Serious game evaluation of a one-hour training basic life support session for secondary school students: new tools for future bystanders S. Gaudry, V. Desailly, P. Pasquier, PB Brun, AT Tesnieres, JD Ricard, D. Dreyfuss, A. Mignon P307 - Public and clinical staff perceptions and knowledge of CPR compared to local and national data J. C White, A. Molokhia, A. Dean, A. Stilwell, G. Friedlaender P308 Dispatcher-assisted telephone cardiopulmonary resuscitation using a French-language compression-ventilation pediatric protocol M. Peters, S. Stipulante, A. Delfosse, AF Donneau, A. Ghuysen P309 Dantrolene versus amiodarone for resuscitation – an experimental study C. Feldmann, D. Freitag, W. Dersch, M. Irqsusi, D. Eschbach, T. Steinfeldt, H. Wulf, T. Wiesmann P310 Long term survival and functional neurological outcome in comatose survivors undergoing therapeutic hypothermia N. Kongpolprom, J. Cholkraisuwat P311 Impact of kidney disease on mortality and neurological outcome in out-of-hospital cardiac arrest: a prospective observational study S. Beitland , E. Nakstad, H. Stær-Jensen , T. Drægni , G. Andersen , D. Jacobsen , C. Brunborg, B. Waldum-Grevbo , K. Sunde P312 ICU dependency of patients admitted after primary percutaneous coronary intervention (PPCI) following out of the hospital cardiac arrest K. Hoyland, D. Pandit P313 Prognostic indicators and outcome prediction model for patients with return of spontaneous circulation from cardiopulmonary arrest: comprehensive registry of in-hospital intensive care on OHCA survival (critical) study in Osaka, Japan K. Hayakawa P314 Cerebral oxygen saturation during resuscitation in a porcine model of cardiac arrest E. Oloktsidou, K. Kotzampassi, B. Fyntanidou, S. Patsatzakis, L. Loukipoudi, E. Doumaki, V. Grosomanidis P315 Presumption of cardiopulmonary resuscitation for sustaining cerebral oxidation using regional cerebral saturation of oxygen: observational cohort study (press study) H. Yasuda P316 EEG reactivity in patients after cardiac arrest: a close look at stimuli MM Admiraal, M. Van Assen, MJ Van Putten, M. Tjepkema-Cloostermans, AF Van Rootselaar, J. Horn P317 Prognostic value of neuron-specific enolase after cardiac arrest F. Ragusa, A. Marudi , S. Baroni, A. Gaspari, E. Bertellini P318 Correlation between electroencephalographic findings and serum neuron specific enolase with outcome of post cardiac arrest patients A. Taha, T. Abdullah, S. Abdel Monem P319 Introduction of a targeted temperature management strategy following cardiac arrest in a district general hospital intensive care unit. S. Alcorn, S. McNeill, S. Russell P320 The evolution of cerebral oxygen saturation in post-cardiac arrest patients treated with therapeutic hypothermia W. Eertmans, C. Genbrugge, I. Meex, J. Dens, F. Jans, C. De Deyne P321 Prognostic factors and neurological outcomes of therapeutic hypothermia in comatose survivors from cardiac arrest: 8-year single center experience J. Cholkraisuwat, N. Kongpolprom P322 Adherence to targeted temperature management after out of hospital cardiac arrest B. Avard, R. Burns P323 Implementation of a therapeutic hypothermia protocol for comatose survivors of out-of-hospital cardiac arrest. A. Patarchi, T. Spina P324 Factors associated with ventilator weaning after targeted temperature management for cardiac arrest patients in japan H. Tanaka, N. Otani, S. Ode, S. Ishimatsu P325 Differential activation of c-fos in paraventricular nuclei of the hypothalamus and thalamus of the rat following myocardial infarction J. Cho, J. B. Moon, C. W. Park, T. G. Ohk, M. C. Shin, M. H. Won P326 Monitoring of cTroponin I in patients with acute ischemic stroke - predictor of inhospital mortality S. Dakova, Z. Ramsheva, K. Ramshev P327 Hyperthermic preconditioning severely accelerates neuronal damage in the gerbil ischemic hippocampal dentate gyrus via decreasing sods expressions J. Cho, J. B. Moon, C. W. Park, T. G. Ohk, M. C. Shin P328 Failure in neuroprotection of remote limb ischemic post conditioning in the hippocampus of a gerbil model of transient cerebral ischemia J. Cho, J. B. Moon, C. W. Park, T. G. Ohk, M. C. Shin P329 Brain death and admission diagnosis in neurologic intensive care unit, a correlation? A Marudi, S Baroni, A Gaspari, E Bertellini P330 Brain magnetic resonance imaging findings in patients with septic shock G. Orhun, E. Senturk, P. E. Ozcan, S. Sencer, C. Ulusoy, E. Tuzun, F . Esen P331 Benefits of L-carnitine in valproic acid induced encephalopathy R. Tincu, C. Cobilinschi, D. Tomescu, Z. Ghiorghiu, R. Macovei P332Automatic analysis of EEG reactivity in comatose patients M. Van Assen, M. M. Admiraal, M. J. Van Putten, M. Tjepkema-Cloostermans, A. F. Van Rootselaar, J. Horn P333 Usefulness of common ICU severity scoring systems in predicting outcome after spontaneous intracerebral hemorrhage M. Fallenius, M. B. Skrifvars, M. Reinikainen, S. Bendel, R. Raj P334 Evalution of patients with suspected subarachnoid haemorrhage and negative ct imaging M. Abu-Habsa, C. Hymers, A. Borowska, H. Sivadhas, S. Sahiba, S. Perkins P335 Timing of endovascular and surgical treatment for aneurysmal subarachnoid haemorrhage: early but not so fast. J. Rubio, J. A. Rubio, R. Sierra P336 Red blood cell transfusion in aneurysmal subarachnoid hemorrhage – the Sahara cohort study S. English, M. Chasse, A. Turgeon, F. Lauzier, D. Griesdale, A. Garland, D. Fergusson, R. Zarychanski, A. Tinmouth, C. Van Walraven, K. Montroy, J. Ziegler, R. Dupont Chouinard, R. Carignan, A. Dhaliwal, C. Lum, J. Sinclair, G. Pagliarello, L. McIntyre P337 - Aneurysmal subarachnoid hemorrhage and anemia: a canadian multi-centre retrospective cohort study S. English, M. Chasse, A. Turgeon, F. Lauzier, D. Griesdale, A. Garland, D. Fergusson, R. Zarychanski, A. Tinmouth, C. Van Walraven, K. Montroy, J. Ziegler, R. Dupont Chouinard, R. Carignan, A. Dhaliwal, C. Lum, J. Sinclair, G. Pagliarello, L. McIntyre P338 - Does the neutrophil-to-lymphocyte (NLR) ratio predict symptomatic vasospasm or delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH)? T. Groza, N. Moreau, D. Castanares-Zapatero, P. Hantson P339 - ICU-acquired infections in aneurysmal subarachnoid hemorrhage patients: impact on ICU and hospital length of stay M. Carbonara , F. Ortolano, T. Zoerle, S. Magnoni, S. Pifferi, V. Conte, N. Stocchetti P340 - Cerebral metabolic effects of normobaric hyperoxia during the acute phase of aneurysmal subarachnoid hemorrhage L. Carteron, T. Suys, C. Patet, H. Quintard, M. Oddo P341 - Postoperative care for elective craniotomy: where is best done? J. A. Rubio, J. Rubio, R. Sierra P342 - 5-year follow-up of patients after transplantation of organs from donors from neurocritical care V. Spatenkova, E. Pokorna, P. Suchomel P343 - Evaluation of levetiracetam pharmacokinetics after severe traumatic brain injury in neurocritical care patients at a level one trauma center N. Ebert, J. Jancik, H. Rhodes P344 - Model based time series cluster analysis to determine unique patient states in traumatic brain injury T. Bylinski, C. Hawthorne, M. Shaw, I. Piper, J. Kinsella P345 - Brain compartment monitoring capabilities from ICP to BI (bioimpedance) during HS (hypertonic saline) administration. State of art simulation outcome depending on brain swelling type A. K. Kink , I. R. Rätsep P346 - Transfusion of red blood cells in patients with traumatic brain injury admitted to Canadian trauma health centers: a multicenter cohort study A. Boutin, L. Moore, M. Chasse, R. Zarychanski, F. Lauzier, S. English, L. McIntyre, J. Lacroix, D. Griesdale, P. Lessard-Bonaventure, A. F. 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Bielka P377 - Hemodynamic effects of dexmedetomidine in a porcine model of septic shock Z. Aidoni, V. Grosomanidis, K. Kotzampassi, G. Stavrou, B. Fyntanidou, S. Patsatzakis, C. Skourtis P378 - Ketamine for analgosedation in severe hypoxic respiratory failure S. D. Lee, K. Williams, I. D. Weltes P379 - Madness from the moon? lunar cycle and the incidence of delirium on the intensive care unit S. Berhane, C. Arrowsmith, C. Peters, S. Robert P380 - Impaired dynamic cerebral autoregulation after coronary artery bypass grafting and association with postoperative delirium J. Caldas, R. B. Panerai, T. G. Robinson, L. Camara, G. Ferreira, E. Borg-Seng-Shu, M. De Lima Oliveira, N. C. Mian, L. Santos, R. Nogueira, S. P. Zeferino, M. Jacobsen Teixeira, F. Galas, L. A. Hajjar P381 - Risk factors predicting prolonged intensive care unit length of stay after major elective surgery. P. Killeen, M. McPhail, W. Bernal, J. Maggs, J. Wendon, T. Hughes P382 - Systemic inflammatory response syndrome criteria and hospital mortality prediction in a brazilian cohort of critically ill patients L. U. Taniguchi, E. M. Siqueira, J. M. Vieira Jr, L. C. Azevedo P383 - Evaluating the efficacy of a risk predictor panel in identifying patients at elevated risk of morbidity following emergency admission A. N. Ahmad, M. Abu-Habsa, R. Bahl, E. Helme, S. Hadfield, R. Loveridge P384 - A retrospective comparison of outcomes for elective surgical patients admitted post-operatively to the critical care unit or general ward J. Shak, C. Senver, R. Howard-Griffin P385 - Effect of obesity on mortality in surgical critically ill patients. P. Wacharasint, P. Fuengfoo, N. Sukcharoen, R. Rangsin P386 - The national early warning score (news) reliably improves adverse clinical outcome prediction in community-acquired pneumonia - results from a 6 year follow-up D. Sbiti-Rohr, P. 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S.', 'Giamarellos-Bourboulis, E.', 'Tziolos, N.', 'Routsi, C.', 'Katsenos, C.', 'Tsangaris, I.', 'Pneumatikos, I.', 'Vlachogiannis, G.', 'Theodorou, V.', 'Prekates, A.', 'Antypa, E.', 'Koulouras, V.', 'Kapravelos, N.', 'Gogos, C.', 'Antoniadou, E.', 'Mandragos, K.', 'Armaganidis, A.', 'Robles Caballero, A. R.', 'Civantos, B.', 'Figueira, J. C.', 'López, J.', 'Silva-Pinto, A.', 'Ceia, F.', 'Sarmento, A.', 'Santos, L.', 'Almekhlafi, G.', 'Sakr, Y.', 'Al-Dorzi, H.', 'Khan, R.', 'Baharoon, S.', 'Aldawood, A.', 'Matroud, A.', 'Alchin, J.', 'Al Johani, S.', 'Balkhy, H.', 'Arabi, Y.', 'Alsolamy, S.', 'Yousif, S. Y.', 'Alotabi, B. O.', 'Alsaawi, A. S.', 'Ang, J.', 'Curran, M. D.', 'Enoch, D.', 'Navapurkar, V.', 'Morris, A.', 'Sharvill, R.', 'Astin, J.', 'Heredia-Rodríguez, M.', 'Gómez-Sánchez, E.', 'Peláez-Jareño, M. T.', 'Gómez-Pesquera, E.', 'Lorenzo-López, M.', 'Liu-Zhu, P.', 'Aragón-Camino, M.', 'Hernández-Lozano, A.', 'Sánchez-López, A.', 'Álvarez-Fuente, E.', 'Tamayo, E.', 'Patel, J.', 'Kruger, C.', 'O’Neal, J.', 'Rhodes, H.', 'Jancik, J.', 'François, B.', 'Laterre, P. F.', 'Eggimann, P.', 'Torres, A.', 'Sánchez, M.', 'Dequin, P. F.', 'Bassi, G. L.', 'Chastre, J.', 'Jafri, H. S.', 'Ben Romdhane, M.', 'Douira, Z.', 'Kamoun, S.', 'Bousselmi, M.', 'Ben Souissi, A.', 'Boussarsar, Y.', 'Riahi, A.', 'Mebazaa, M. S.', 'Vakalos, A.', 'Avramidis, V.', 'Craven, T. H.', 'Wojcik, G.', 'Kefala, K.', 'McCoubrey, J.', 'Reilly, J.', 'Paterson, R.', 'Inverarity, D.', 'Laurenson, I.', 'Walsh, T. S.', 'Mongodi, S.', 'Bouhemad, B.', 'Orlando, A.', 'Stella, A.', 'Via, G.', 'Iotti, G.', 'Braschi, A.', 'Mojoli, F.', 'Haliloglu, M.', 'Bilgili, B.', 'Kasapoglu, U.', 'Sayan, I.', 'Süzer Aslan, M.', 'Yalcın, A.', 'Cinel, I.', 'Vakalos, A.', 'Avramidis, V.', 'Ellis, H. E.', 'Bauchmuller, K.', 'Miller, D.', 'Temple, A.', 'Chastre, J.', 'François, B.', 'Torres, A.', 'Luyt, C. E.', 'Sánchez, M.', 'Singer, M.', 'Jafri, H. S.', 'Nassar, Y.', 'Ayad, M. S.', 'Trifi, A.', 'Abdellatif, S.', 'Daly, F.', 'Nasri, R.', 'Ben Lakhal, S.', 'Bilgili, B.', 'Haliloglu, M.', 'Gul, F.', 'Cinel, I.', 'Kuzovlev, A.', 'Shabanov, A.', 'Polovnikov, S.', 'Moroz, V.', 'Kadrichu, N.', 'Dang, T.', 'Corkery, K.', 'Challoner, P.', 'Bassi, G. Li', 'Aguilera, E.', 'Chiurazzi, C.', 'Travierso, C.', 'Motos, A.', 'Fernandez, L.', 'Amaro, R.', 'Senussi, T.', 'Idone, F.', 'Bobi, J.', 'Rigol, M.', 'Torres, A.', 'Hodiamont, C. J.', 'Juffermans, N. P.', 'Janssen, J. M.', 'Bouman, C. S.', 'Mathôt, R. A.', 'De Jong, M. D.', 'Van Hest, R. M.', 'Payne, L.', 'Fraser, G. L.', 'Tudor, B.', 'Lahner, M.', 'Roth, G.', 'Krenn, C.', 'Talaie, H.', 'Jault, P.', 'Gabard, J.', 'Leclerc, T.', 'Jennes, S.', 'Que, Y.', 'Rousseau, A.', 'Ravat, F.', 'Al-Dorzi, H.', 'Eissa, A.', 'Al-Harbi, S.', 'Aldabbagh, T.', 'Khan, R.', 'Arabi, Y.', 'Trifi, A.', 'Abdellatif., S.', 'Daly, F.', 'Nasri, R.', 'Ben Lakhal, S.', 'Paramba, F.', 'Purayil, N.', 'Naushad, V.', 'Mohammad, O.', 'Negi, V.', 'Chandra, P.', 'Kleinsasser, A.', 'Witrz, M. R.', 'Buchner-Doeven, J. F.', 'Tuip-de Boer, A. M.', 'Goslings, J. C.', 'Juffermans, N. P.', 'Van Hezel, M.', 'Straat, M.', 'Boing, A', 'Van Bruggen, R', 'Juffermans, N', 'Markopoulou, D.', 'Venetsanou, K.', 'Kaldis, V.', 'Koutete, D.', 'Chroni, D.', 'Alamanos, I.', 'Koch, L.', 'Jancik, J.', 'Rhodes, H.', 'Walter, E.', 'Maekawa, K.', 'Hayakawa, M.', 'Kushimoto, S.', 'Shiraishi, A.', 'Kato, H.', 'Sasaki, J.', 'Ogura, H.', 'Matauoka, T.', 'Uejima, T.', 'Morimura, N.', 'Ishikura, H.', 'Hagiwara, A.', 'Takeda, M.', 'Tarabrin, O.', 'Shcherbakow, S.', 'Gavrychenko, D.', 'Mazurenko, G.', 'Ivanova, V.', 'Chystikov, O.', 'Plourde, C.', 'Lessard, J.', 'Chauny, J.', 'Daoust, R.', 'Shcherbakow, S.', 'Tarabrin, O.', 'Gavrychenko, D.', 'Mazurenko, G.', 'Chystikov, O.', 'Vakalos, A.', 'Avramidis, V.', 'Kropman, L.', 'In het Panhuis, L.', 'Konings, J.', 'Huskens, D.', 'Schurgers, E.', 'Roest, M.', 'De Laat, B.', 'Lance, M.', 'Durila, M.', 'Lukas, P.', 'Astraverkhava, M.', 'Jonas, J.', 'Budnik, I.', 'Shenkman, B.', 'Hayami, H.', 'Koide, Y.', 'Goto, T.', 'Iqbal, R.', 'Alhamdi, Y.', 'Venugopal, N.', 'Abrams, S.', 'Downey, C.', 'Toh, C. H.', 'Welters, I. D.', 'Bombay, V. B.', 'Chauny, J. M.', 'Daoust, R. D.', 'Lessard, J. L.', 'Marquis, M. M.', 'Paquet, J. P.', 'Siemens, K.', 'Sangaran, D.', 'Hunt, B. J.', 'Durward, A.', 'Nyman, A.', 'Murdoch, I. A.', 'Tibby, S. M.', 'Ampatzidou, F.', 'Moisidou, D.', 'Dalampini, E.', 'Nastou, M.', 'Vasilarou, E.', 'Kalaizi, V.', 'Chatzikostenoglou, H.', 'Drossos, G.', 'Spadaro, S.', 'Fogagnolo, A.', 'Fiore, T.', 'Schiavi, A.', 'Fontana, V.', 'Taccone, F.', 'Volta, C.', 'Chochliourou, E.', 'Volakli, E.', 'Violaki, A.', 'Samkinidou, E.', 'Evlavis, G.', 'Panagiotidou, V.', 'Sdougka, M.', 'Mothukuri, R.', 'Battle, C.', 'Guy, K.', 'Mills, G.', 'Evans, P.', 'Wijesuriya, J.', 'Keogh, S.', 'Docherty, A.', 'O’Donnell, R.', 'Brunskill, S.', 'Trivella, M.', 'Doree, C.', 'Holst, L.', 'Parker, M.', 'Gregersen, M.', 'Almeida, J.', 'Walsh, T.', 'Stanworth, S.', 'Moravcova, S.', 'Mansell, J.', 'Rogers, A.', 'Smith, R. A.', 'Hamilton-Davies, C.', 'Omar, A.', 'Allam, M.', 'Bilala, O.', 'Kindawi, A.', 'Ewila, H.', 'Ampatzidou, F.', 'Moisidou, D.', 'Nastou, M.', 'Dalampini, E.', 'Malamas, A.', 'Vasilarou, E.', 'Drossos, G.', 'Ferreira, G.', 'Caldas, J.', 'Fukushima, J.', 'Osawa, E. A.', 'Arita, E.', 'Camara, L.', 'Zeferino, S.', 'Jardim, J.', 'Gaioto, F.', 'Dallan, L.', 'Jatene, F. B.', 'Kalil Filho, R.', 'Galas, F.', 'Hajjar, L. A.', 'Mitaka, C.', 'Ohnuma, T.', 'Murayama, T.', 'Kunimoto, F.', 'Nagashima, M.', 'Takei, T.', 'Tomita, M.', 'Omar, A.', 'Mahmoud, K.', 'Hanoura, S.', 'Sudarsanan, S.', 'Sivadasan, P.', 'Othamn, H.', 'Shouman, Y.', 'Singh, R.', 'Al Khulaifi, A.', 'Mandel, I.', 'Mikheev, S.', 'Suhodolo, I.', 'Kiselev, V.', 'Svirko, Y.', 'Podoksenov, Y.', 'Jenkins, S. A.', 'Griffin, R.', 'Tovar Doncel, M. S.', 'Lima, A.', 'Aldecoa, C.', 'Ince, C.', 'Taha, A.', 'Shafie, A.', 'Mostafa, M.', 'Syed, N.', 'Hon, H.', 'Righetti, F.', 'Colombaroli, E.', 'Castellano, G.', 'Righetti, F.', 'Colombaroli, E.', 'Hravnak, M.', 'Chen, L. C.', 'Dubrawski, A. D.', 'Clermont, G. C.', 'Pinsky, M. R.', 'Gonzalez, S.', 'Macias, D.', 'Acosta, J.', 'Jimenez, P.', 'Loza, A.', 'Lesmes, A.', 'Lucena, F.', 'Leon, C.', 'Tovar Doncel, M. S.', 'Ince, C.', 'Aldecoa, C.', 'Lima, A.', 'Bastide, M.', 'Richecoeur, J.', 'Frenoy, E.', 'Lemaire, C.', 'Sauneuf, B.', 'Tamion, F.', 'Nseir, S.', 'Du Cheyron, D.', 'Dupont, H.', 'Maizel, J.', 'Shaban, M.', 'Kolko, R.', 'Salahuddin, N.', 'Sharshir, M.', 'AbuRageila, M.', 'AlHussain, A.', 'Mercado, P.', 'Maizel, J.', 'Kontar, L.', 'Titeca, D.', 'Brazier, F.', 'Riviere, A.', 'Joris, M.', 'Soupison, T.', 'De Cagny, B.', 'Slama, M.', 'Wagner, J.', 'Körner, A.', 'Kubik, M.', 'Kluge, S.', 'Reuter, D.', 'Saugel, B.', 'Colombaroli, E.', 'Righetti, F.', 'Castellano, G.', 'Tran, T.', 'De Bels, D.', 'Cudia, A.', 'Strachinaru, M.', 'Ghottignies, P.', 'Devriendt, J.', 'Pierrakos, C.', 'Martínez González, Ó.', 'Blancas, R.', 'Luján, J.', 'Ballesteros, D.', 'Martínez Díaz, C.', 'Núñez, A.', 'Martín Parra, C.', 'López Matamala, B.', 'Alonso Fernández, M.', 'Chana, M.', 'Huber, W.', 'Eckmann, M.', 'Elkmann, F.', 'Gruber, A.', 'Klein, I.', 'Schmid, R. M.', 'Lahmer, T.', 'Moller, P. W.', 'Sondergaard, S.', 'Jakob, S. M.', 'Takala, J.', 'Berger, D.', 'Bastoni, D.', 'Aya, H.', 'Toscani, L.', 'Pigozzi, L.', 'Rhodes, A.', 'Cecconi, M.', 'Ostrowska, C.', 'Aya, H.', 'Abbas, A.', 'Mellinghoff, J.', 'Ryan, C.', 'Dawson, D.', 'Rhodes, A.', 'Cecconi, M.', 'Cronhjort, M.', 'Wall, O.', 'Nyberg, E.', 'Zeng, R.', 'Svensen, C.', 'Mårtensson, J.', 'Joelsson-Alm, E.', 'Aguilar Arzapalo, M.', 'Barradas, L.', 'Lopez, V.', 'Cetina, M.', 'Parenti, N.', 'Palazzi, C.', 'Amidei, L. A.', 'Borrelli, F. B.', 'Campanale, S. C.', 'Tagliazucchi, F. T.', 'Sedoni, G. S.', 'Lucchesi, D. L.', 'Carella, E. C.', 'Luciani, A. L', 'Mackovic, M.', 'Maric, N.', 'Bakula, M.', 'Aya, H.', 'Rhodes, A.', 'Grounds, R. M.', 'Fletcher, N.', 'Cecconi, M.', 'Avard, B.', 'Zhang, P.', 'Mezidi, M.', 'Charbit, J.', 'Ould-Chikh, M.', 'Deras, P.', 'Maury, C.', 'Martinez, O.', 'Capdevila, X.', 'Hou, P.', 'Linde-Zwirble, W. Z.', 'Douglas, I. D.', 'Shapiro, N. S.', 'Ben Souissi, A.', 'Mezghani, I.', 'Ben Aicha, Y.', 'Kamoun, S.', 'Laribi, B.', 'Jeribi, B.', 'Riahi, A.', 'Mebazaa, M. S.', 'Pereira, C.', 'Marinho, R.', 'Antunes, R.', 'Marinho, A.', 'Crivits, M.', 'Raes, M.', 'Decruyenaere, J.', 'Hoste, E.', 'Bagin, V.', 'Rudnov, V.', 'Savitsky, A.', 'Astafyeva, M.', 'Korobko, I.', 'Vein, V.', 'Kampmeier, T.', 'Arnemann, P.', 'Hessler, M.', 'Wald, A.', 'Bockbreder, K.', 'Morelli, A.', 'Van Aken, H.', 'Rehberg, S.', 'Ertmer, C.', 'Arnemann, P.', 'Hessler, M.', 'Kampmeier, T.', 'Rehberg, S.', 'Van Aken, H.', 'Ince, C.', 'Ertmer, C.', 'Reddy, S.', 'Bailey, M.', 'Beasley, R.', 'Bellomo, R.', 'Mackle, D.', 'Psirides, A.', 'Young, P.', 'Reddy, S.', 'Bailey, M.', 'Beasley, R.', 'Bellomo, R.', 'Mackle, D.', 'Young, P.', 'Venkatesh, H.', 'Ramachandran, S.', 'Basu, A.', 'Nair, H.', 'Egan, S.', 'Bates, J.', 'Oliveira, S.', 'Rangel Neto, N. R.', 'Reis, F. Q.', 'Lee, C. P.', 'Lin, X. L.', 'Choong, C.', 'Eu, K. M.', 'Sim, W. Y.', 'Tee, K. S.', 'Pau, J.', 'Abisheganaden, J.', 'Maas, K.', 'De Geus, H.', 'Lafuente, E.', 'Marinho, R.', 'Moura, J.', 'Antunes, R.', 'Marinho, A.', 'Doris, T. E.', 'Monkhouse, D.', 'Shipley, T.', 'Kardasz, S.', 'Gonzalez, I', 'Stads, S.', 'Groeneveld, A. J.', 'Elsayed, I.', 'Ward, N.', 'Tridente, A.', 'Raithatha, A.', 'Steuber, A.', 'Pelletier, C.', 'Schroeder, S.', 'Michael, E.', 'Slowinski, T.', 'Kindgen-Milles, D.', 'Ghabina, S.', 'Turani, F.', 'Belli, A.', 'Busatti, S.', 'Barettin, G.', 'Candidi, F.', 'Gargano, F.', 'Barchetta, R.', 'Falco, M.', 'Demirkiran, O.', 'Kosuk, M.', 'Bozbay, S.', 'Weber, V.', 'Hartmann, J.', 'Harm, S.', 'Linsberger, I.', 'Eichhorn, T.', 'Valicek, G.', 'Miestinger, G.', 'Hoermann, C.', 'Faenza, S.', 'Ricci, D.', 'Mancini, E.', 'Gemelli, C.', 'Cuoghi, A.', 'Magnani, S.', 'Atti, M.', 'Laddomada, T.', 'Doronzio, A.', 'Balicco, B.', 'Gruda, M. C.', 'O’Sullivan, P.', 'Dan, V. P.', 'Guliashvili, T.', 'Scheirer, A.', 'Golobish, T. D.', 'Capponi, V. J.', 'Chan, P. P.', 'Kogelmann, K.', 'Drüner, M.', 'Jarczak, D.', 'Turani, F.', 'Belli, A. B.', 'Martni, S. M.', 'Cotticelli, V. C.', 'Mounajergi, F.', 'Barchetta, R.', 'Morimoto, S.', 'Ishikura, H.', 'Hussain, I.', 'Salahuddin, N.', 'Nadeem, A.', 'Ghorab, K.', 'Maghrabi, K.', 'Kloesel, S. K.', 'Goldfuss, C.', 'Stieglitz, A.', 'Stieglitz, A. S.', 'Krstevska, L.', 'Albuszies, G.', 'Aguilar Arzapalo, M.', 'Barradas, L.', 'Lopez, V.', 'Escalante, A.', 'Jimmy, G.', 'Cetina, M.', 'Izawa, J.', 'Iwami, T.', 'Uchino, S.', 'Takinami, M.', 'Kitamura, T.', 'Kawamura, T.', 'Powell-Tuck, J. G.', 'Crichton, S.', 'Raimundo, M.', 'Camporota, L.', 'Wyncoll, D.', 'Ostermann, M.', 'Hana, A.', 'De Geus, H. R.', 'De Geus, H. R.', 'Hana, A.', 'Aydogdu, M.', 'Boyaci, N.', 'Yuksel, S.', 'Gursel, G.', 'Cayci Sivri, A. B.', 'Meza-Márquez, J.', 'Nava-López, J.', 'Carrillo-Esper, R.', 'Dardashti, A.', 'Grubb, A.', 'Maizel, J.', 'Wetzstein, M.', 'Titeca, D.', 'Kontar, L.', 'Brazier, F.', 'De Cagny, B.', 'Riviere, A.', 'Soupison, T.', 'Joris, M.', 'Slama, M.', 'Peters, E.', 'Njimi, H.', 'Pickkers, P.', 'Vincent, J. L.', 'Waraich, M.', 'Doyle, J.', 'Samuels, T.', 'Forni, L.', 'Desai, N.', 'Baumber, R.', 'Gunning, P.', 'Sell, A.', 'Lin, S.', 'Torrence, H.', 'O’Dwyer, M.', 'Kirwan, C.', 'Prowle, J.', 'Kim, T.', 'O’Connor, M. E.', 'Hewson, R. W.', 'Kirwan, C. J.', 'Pearse, R. M.', 'Prowle, J.', 'Hanoura, S.', 'Omar, A.', 'Othamn, H.', 'Sudarsanan, S.', 'Allam, M.', 'Maksoud, M.', 'Singh, R.', 'Al Khulaifi, A.', 'O’Connor, M. E.', 'Hewson, R. W.', 'Kirwan, C. J.', 'Pearse, R. M.', 'Prowle, J.', 'Uzundere, O.', 'Memis, D.', 'Ýnal, M.', 'Gultekin, A.', 'Turan, N.', 'Aydin, M. A.', 'Basar, H.', 'Sencan, I.', 'Kapuagasi, A.', 'Ozturk, M.', 'Uzundurukan, Z.', 'Gokmen, D.', 'Ozcan, A.', 'Kaymak, C.', 'Artemenko, V. A.', 'Budnyuk, A.', 'Pugh, R.', 'Bhandari, S.', 'Mauri, T.', 'Turrini, C.', 'Langer, T.', 'Taccone, P.', 'Volta, C. A.', 'Marenghi, C.', 'Gattinoni, L.', 'Pesenti, A.', 'Sweeney, L.', 'O’Sullivan, A.', 'Kelly, P.', 'Mukeria, E.', 'MacLoughlin, R.', 'Pfeffer, M.', 'Thomas, J. T.', 'Bregman, G. B.', 'Karp, G. K.', 'Kishinevsky, E. K.', 'Stavi, D. S.', 'Adi, N. A.', 'Poropat, T.', 'Knafelj, R.', 'Llopart, E.', 'Batlle, M.', 'De Haro, C.', 'Mesquida, J.', 'Artigas, A.', 'Pavlovic, D.', 'Lewerentz, L.', 'Spassov, A.', 'Schneider, R.', 'De Smet, S.', 'De Raedt, S.', 'Derom, E.', 'Depuydt, P', 'Oeyen, S.', 'Benoit, D.', 'Decruyenaere, J.', 'Gobatto, A.', 'Besen, B.', 'Tierno, P.', 'Melro, L.', 'Mendes, P.', 'Cadamuro, F.', 'Park, M.', 'Malbouisson, L. M.', 'Civantos, B. C.', 'Lopez, J. L.', 'Robles, A.', 'Figueira, J.', 'Yus, S.', 'Garcia, A.', 'Oglinda, A.', 'Ciobanu, G.', 'Oglinda, C.', 'Schirca, L.', 'Sertinean, T.', 'Lupu, V.', 'Kelly, P.', 'O’Sullivan, A.', 'Sweeney, L.', 'MacLoughlin, R.', 'O’Sullivan, A.', 'Kelly, P.', 'Sweeney, L.', 'Mukeria, E.', 'Wolny, M.', 'MacLoughlin, R.', 'Pagano, A.', 'Numis, F.', 'Visone, G.', 'Saldamarco, L.', 'Russo, T.', 'Porta, G.', 'Paladino, F.', 'Bell, C.', 'Liu, J.', 'Debacker, J.', 'Lee, C.', 'Tamberg, E.', 'Campbell, V.', 'Mehta, S.', 'Silva-Pinto, A.', 'Sarmento, A.', 'Santos, L.', 'Kara, Ý.', 'Yýldýrým, F.', 'Zerman, A.', 'Güllü, Z.', 'Boyacý, N.', 'Basarýk Aydogan, B.', 'Gaygýsýz, Ü.', 'Gönderen, K.', 'Arýk, G.', 'Turkoglu, M.', 'Aydogdu, M.', 'Aygencel, G.', 'Ülger, Z.', 'Gursel, G.', 'Boyacý, N.', 'Isýkdogan, Z.', 'Özdedeoglu, Ö.', 'Güllü, Z.', 'Badoglu, M.', 'Gaygýsýz, U.', 'Aydogdu, M.', 'Gursel, G.', 'Kongpolprom, N.', 'Sittipunt, C.', 'Eden, A.', 'Kokhanovsky, Y.', 'Bursztein – De Myttenaere, S.', 'Pizov, R.', 'Neilans, L.', 'MacIntyre, N.', 'Radosevich, M.', 'Wanta, B.', 'Weber, V.', 'Meyer, T.', 'Smischney, N.', 'Brown, D.', 'Diedrich, D.', 'Fuller, A.', 'McLindon, P.', 'Sim, K.', 'Shoaeir, M.', 'Noeam, K.', 'Mahrous, A.', 'Matsa, R.', 'Ali, A.', 'Dridi, C.', 'Koubaji, S.', 'Kamoun, S.', 'Haddad, F.', 'Ben Souissi, A.', 'Laribi, B.', 'Riahi, A.', 'Mebazaa, M. S.', 'Pérez-Calatayud, A.', 'Carrillo-Esper, R.', 'Zepeda-Mendoza, A.', 'Diaz-Carrillo, M.', 'Arch-Tirado, E.', 'Carbognin, S.', 'Pelacani, L.', 'Zannoni, F.', 'Agnoli, A.', 'Gagliardi, G.', 'Cho, R.', 'Adams, A.', 'Lunos, S.', 'Ambur, S.', 'Shapiro, R.', 'Prekker, M.', 'Thijssen, M.', 'Janssen, L.', 'Foudraine, N.', 'Voscopoulos, C. J.', 'Freeman, J.', 'Voscopoulos, C. J.', 'Freeman, J.', 'George, E.', 'Voscopoulos, C. J.', 'Eversole, D.', 'Freeman, J.', 'George, E.', 'Muttini, S.', 'Bigi, R.', 'Villani, G.', 'Patroniti, N.', 'Williams, G.', 'Voscopoulos, C. J.', 'Freeman, J.', 'George, E', 'Waldmann, A.', 'Böhm, S.', 'Windisch, W.', 'Strassmann, S.', 'Karagiannidis, C.', 'Waldmann, A.', 'Böhm, S.', 'Windisch, W.', 'Strassmann, S.', 'Karagiannidis, C.', 'Karagiannidis, C. K.', 'Waldmann, A. W.', 'Böhm, S. B.', 'Strassmann, S.', 'Windisch, W. W.', 'Persson, P.', 'Lundin, S.', 'Stenqvist, O.', 'Porta, G.', 'Numis, F.', 'Serra, C. S.', 'Pagano, A. P.', 'Masarone, M. M.', 'Rinaldi, L. R.', 'Amelia, A. A.', 'Fascione, M. F.', 'Adinolfi, L. A.', 'Ruggiero, E. R.', 'Asota, F.', 'O’Rourke, K.', 'Ranjan, S.', 'Morgan, P.', 'DeBacker, J. W.', 'Tamberg, E.', 'O’Neill, L.', 'Munshi, L.', 'Burry, L.', 'Fan, E.', 'Mehta, S.', 'Poo, S.', 'Mahendran, K.', 'Fowles, J.', 'Gerrard, C.', 'Vuylsteke, A.', 'Loveridge, R.', 'Chaddock, C.', 'Patel, S.', 'Kakar, V.', 'Willars, C.', 'Hurst, T.', 'Park, C.', 'Best, T.', 'Vercueil, A.', 'Auzinger, G.', 'Borgman, A.', 'Proudfoot, A. G.', 'Grins, E.', 'Emiley, K. E.', 'Schuitema, J.', 'Fitch, S. J.', 'Marco, G.', 'Sturgill, J.', 'Dickinson, M. G.', 'Strueber, M.', 'Khaghani, A.', 'Wilton, P.', 'Jovinge, S. M.', 'Sampson, C.', 'Harris-Fox, S.', 'Cove, M. E.', 'Vu, L. H.', 'Sen, A.', 'Federspiel, W. J.', 'Kellum, J. A.', 'Mazo Torre, C.', 'Riera, J.', 'Ramirez, S.', 'Borgatta, B.', 'Lagunes, L.', 'Rello, J.', 'Kuzovlev, A. 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R.', 'McCarron, E.', 'Simants, S.', 'Patanwala, I.', 'Welters, I.', 'Su, Y.', 'Fernández Villanueva, J.', 'Fernández Garda, R.', 'López Lago, A.', 'Rodríguez Ruíz, E.', 'Hernández Vaquero, R.', 'Tomé Martínez de Rituerto, S.', 'Varo Pérez, E.', 'Lefel, N.', 'Schaap, F.', 'Bergmans, D.', 'Olde Damink, S.', 'Van de Poll, M.', 'Tizard, K.', 'Lister, C.', 'Poole, L.', 'Ringaitiene, D.', 'Gineityte, D.', 'Vicka, V.', 'Norkiene, I.', 'Sipylaite, J.', 'O’Loughlin, A.', 'Maraj, V.', 'Dowling, J.', 'Velasco, M. B.', 'Dalcomune, D. M.', 'Dias, E. B.', 'Fernandes, S. L.', 'Oshima, T.', 'Graf, S.', 'Heidegger, C.', 'Genton, L.', 'Karsegard, V.', 'Dupertuis, Y.', 'Pichard, C.', 'Friedli, N.', 'Stanga, Z.', 'Mueller, B.', 'Schuetz, P.', 'Vandersteen, L.', 'Stessel, B.', 'Evers, S.', 'Van Assche, A.', 'Jamaer, L.', 'Dubois, J.', 'Marinho, R.', 'Castro, H.', 'Moura, J.', 'Valente, J.', 'Martins, P.', 'Casteloes, P.', 'Magalhaes, C.', 'Cabral, S.', 'Santos, M.', 'Oliveira, B.', 'Salgueiro, A.', 'Marinho, A.', 'Marinho, R.', 'Santos, M.', 'Lafuente, E.', 'Castro, H.', 'Cabral, S.', 'Moura, J.', 'Martins, P.', 'Oliveira, B.', 'Salgueiro, A.', 'Duarte, S.', 'Castro, S.', 'Melo, M.', 'Casteloes, P.', 'Marinho, A.', 'Gray, S.', 'Maipang, K.', 'Bhurayanontachai, R.', 'Grädel, L. G.', 'Schütz, P.', 'Langlois, P.', 'Manzanares, W.', 'Tincu, R.', 'Cobilinschi, C.', 'Tomescu, D.', 'Ghiorghiu, Z.', 'Macovei, R.', 'Manzanares, W.', 'Langlois, P.', 'Lemieux, M.', 'Elke, G.', 'Bloos, F.', 'Reinhart, K.', 'Heyland, D.', 'Langlois, P.', 'Lemieux, M.', 'Aramendi, I.', 'Heyland, D.', 'Manzanares, W.', 'Su, Y.', 'Marinho, R.', 'Babo, N.', 'Marinho, A.', 'Hoshino, M.', 'Haraguchi, Y.', 'Kajiwara, S.', 'Mitsuhashi, T.', 'Tsubata, T.', 'Aida, M.', 'Rattanapraphat, T.', 'Bhurayanontachai, R.', 'Kongkamol, C.', 'Khwannimit, B.', 'Marinho, R.', 'Santos, M.', 'Castro, H.', 'Lafuente, E.', 'Salgueiro, A.', 'Cabral, S.', 'Martins, P.', 'Moura, J.', 'Oliveira, B.', 'Melo, M.', 'Xavier, B.', 'Valente, J.', 'Magalhaes, C.', 'Casteloes, P.', 'Marinho, A.', 'Moisidou, D.', 'Ampatzidou, F.', 'Koutsogiannidis, C.', 'Moschopoulou, M.', 'Drossos, G.', 'Taskin, G.', 'Çakir, M.', 'Güler, AK', 'Taskin, A.', 'Öcal, N.', 'Özer, S.', 'Yamanel, L.', 'Wong, J. M.', 'Fitton, C.', 'Anwar, S.', 'Stacey, S.', 'Aggou, M.', 'Fyntanidou, B.', 'Patsatzakis, S.', 'Oloktsidou, E.', 'Lolakos, K.', 'Papapostolou, E.', 'Grosomanidis, V.', 'Suda, S.', 'Ikeda, T.', 'Ono, S.', 'Ueno, T.', 'Izutani, Y.', 'Gaudry, S.', 'Desailly, V.', 'Pasquier, P.', 'Brun, PB', 'Tesnieres, AT', 'Ricard, JD', 'Dreyfuss, D.', 'Mignon, A.', 'White, J. C', 'Molokhia, A.', 'Dean, A.', 'Stilwell, A.', 'Friedlaender, G.', 'Peters, M.', 'Stipulante, S.', 'Delfosse, A.', 'Donneau, AF', 'Ghuysen, A.', 'Feldmann, C.', 'Freitag, D.', 'Dersch, W.', 'Irqsusi, M.', 'Eschbach, D.', 'Steinfeldt, T.', 'Wulf, H.', 'Wiesmann, T.', 'Kongpolprom, N.', 'Cholkraisuwat, J.', 'Beitland, S.', 'Nakstad, E.', 'Stær-Jensen, H.', 'Drægni, T.', 'Andersen, G.', 'Jacobsen, D.', 'Brunborg, C.', 'Waldum-Grevbo, B.', 'Sunde, K.', 'Hoyland, K.', 'Pandit, D.', 'Hayakawa, K.', 'Oloktsidou, E.', 'Kotzampassi, K.', 'Fyntanidou, B.', 'Patsatzakis, S.', 'Loukipoudi, L.', 'Doumaki, E.', 'Grosomanidis, V.', 'Yasuda, H.', 'Admiraal, M. M.', 'Van Assen, M.', 'Van Putten, M. J.', 'Tjepkema-Cloostermans, M.', 'Van Rootselaar, A. F.', 'Horn, J.', 'Ragusa, F.', 'Marudi, A.', 'Baroni, S.', 'Gaspari, A.', 'Bertellini, E.', 'Taha, A.', 'Abdullah, T.', 'Abdel Monem, S.', 'Alcorn, S.', 'McNeill, S.', 'Russell, S.', 'Eertmans, W.', 'Genbrugge, C.', 'Meex, I.', 'Dens, J.', 'Jans, F.', 'De Deyne, C.', 'Cholkraisuwat, J.', 'Kongpolprom, N.', 'Avard, B', 'Burns, R', 'Patarchi, A.', 'Spina, T.', 'Tanaka, H.', 'Otani, N.', 'Ode, S.', 'Ishimatsu, S.', 'Cho, J.', 'Moon, J. B.', 'Park, C. W.', 'Ohk, T. G.', 'Shin, M. C.', 'Won, M. H.', 'Dakova, S.', 'Ramsheva, Z.', 'Ramshev, K.', 'Cho, J.', 'Moon, J. B.', 'Park, C. W.', 'Ohk, T. G.', 'Shin, M. C.', 'Cho, J.', 'Moon, J. B.', 'Park, C. W.', 'Ohk, T. G.', 'Shin, M. C.', 'Marudi, A', 'Baroni, S', 'Gaspari, A', 'Bertellini, E', 'Orhun, G.', 'Senturk, E.', 'Ozcan, P. E.', 'Sencer, S.', 'Ulusoy, C.', 'Tuzun, E.', 'Esen, F.', 'Tincu, R.', 'Cobilinschi, C.', 'Tomescu, D.', 'Ghiorghiu, Z.', 'Macovei, R.', 'Van Assen, M.', 'Admiraal, M. M.', 'Van Putten, M. J.', 'Tjepkema-Cloostermans, M.', 'Van Rootselaar, A. F.', 'Horn, J.', 'Fallenius, M.', 'Skrifvars, M. B.', 'Reinikainen, M.', 'Bendel, S.', 'Raj, R.', 'Abu-Habsa, M.', 'Hymers, C.', 'Borowska, A.', 'Sivadhas, H.', 'Sahiba, S.', 'Perkins, S.', 'Rubio, J.', 'Rubio, J. A.', 'Sierra, R.', 'English, S.', 'Chasse, M.', 'Turgeon, A.', 'Lauzier, F.', 'Griesdale, D.', 'Garland, A.', 'Fergusson, D.', 'Zarychanski, R.', 'Tinmouth, A.', 'Van Walraven, C.', 'Montroy, K.', 'Ziegler, J.', 'Dupont Chouinard, R.', 'Carignan, R.', 'Dhaliwal, A.', 'Lum, C.', 'Sinclair, J.', 'Pagliarello, G.', 'McIntyre, L.', 'English, S.', 'Chasse, M.', 'Turgeon, A.', 'Lauzier, F.', 'Griesdale, D.', 'Garland, A.', 'Fergusson, D.', 'Zarychanski, R.', 'Tinmouth, A.', 'Van Walraven, C.', 'Montroy, K.', 'Ziegler, J.', 'Dupont Chouinard, R.', 'Carignan, R.', 'Dhaliwal, A.', 'Lum, C.', 'Sinclair, J.', 'Pagliarello, G.', 'McIntyre, L.', 'Groza, T.', 'Moreau, N.', 'Castanares-Zapatero, D.', 'Hantson, P.', 'Carbonara, M.', 'Ortolano, F.', 'Zoerle, T.', 'Magnoni, S.', 'Pifferi, S.', 'Conte, V.', 'Stocchetti, N.', 'Carteron, L.', 'Suys, T.', 'Patet, C.', 'Quintard, H.', 'Oddo, M.', 'Rubio, J. A.', 'Rubio, J.', 'Sierra, R.', 'Spatenkova, V.', 'Pokorna, E.', 'Suchomel, P.', 'Ebert, N.', 'Jancik, J.', 'Rhodes, H.', 'Bylinski, T.', 'Hawthorne, C.', 'Shaw, M.', 'Piper, I.', 'Kinsella, J.', 'Kink, A. K.', 'Rätsep, I. R.', 'Boutin, A.', 'Moore, L.', 'Chasse, M.', 'Zarychanski, R.', 'Lauzier, F.', 'English, S.', 'McIntyre, L.', 'Lacroix, J.', 'Griesdale, D.', 'Lessard-Bonaventure, P.', 'Turgeon, A. F.', 'Boutin, A.', 'Moore, L.', 'Green, R.', 'Lessard-Bonaventure, P.', 'Erdogan, M.', 'Butler, M.', 'Lauzier, F.', 'Chasse, M.', 'English, S.', 'McIntyre, L.', 'Zarychanski, R.', 'Lacroix, J.', 'Griesdale, D.', 'Desjardins, P.', 'Fergusson, D. A.', 'Turgeon, A. F.', 'Goncalves, B.', 'Vidal, B.', 'Valdez, C.', 'Rodrigues, A. C.', 'Miguez, L.', 'Moralez, G.', 'Hong, T.', 'Kutz, A.', 'Hausfater, P.', 'Amin, D.', 'Struja, T.', 'Haubitz, S.', 'Huber, A.', 'Mueller, B.', 'Schuetz, P.', 'Brown, T.', 'Collinson, J.', 'Pritchett, C.', 'Slade, T.', 'Le Guen, M.', 'Hellings, S.', 'Ramsaran, R.', 'Alsheikhly, A.', 'Abe, T.', 'Kanapeckaite, L.', 'Abu-Habsa, M.', 'Bahl, R.', 'Russell, M. Q.', 'Real, K. J.', 'Abu-Habsa, M.', 'Lyon, R. M.', 'Oveland, N. P.', 'Penketh, J.', 'Mcdonald, M.', 'Kelly, F.', 'Alfafi, M.', 'Alsolamy, S.', 'Almutairi, W.', 'Alotaibi, B.', 'Van den Berg, A. E', 'Schriel, Y.', 'Dawson, L.', 'Meynaar, I. A.', 'Talaie, H.', 'Silva, D.', 'Fernandes, S.', 'Gouveia, J.', 'Santos Silva, J.', 'Foley, J.', 'Kaskovagheorgescu, A.', 'Evoy, D.', 'Cronin, J.', 'Ryan, J.', 'Huck, M.', 'Hoffmann, C.', 'Renner, J.', 'Laitselart, P.', 'Donat, N.', 'Cirodde, A.', 'Schaal, J. 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D.', 'Berhane, S.', 'Arrowsmith, C.', 'Peters, C.', 'Robert, S.', 'Caldas, J.', 'Panerai, R. B.', 'Robinson, T. G.', 'Camara, L.', 'Ferreira, G.', 'Borg-Seng-Shu, E.', 'De Lima Oliveira, M.', 'Mian, N. C.', 'Santos, L.', 'Nogueira, R.', 'Zeferino, S. P.', 'Jacobsen Teixeira, M.', 'Galas, F.', 'Hajjar, L. A.', 'Killeen, P.', 'McPhail, M.', 'Bernal, W.', 'Maggs, J.', 'Wendon, J.', 'Hughes, T.', 'Taniguchi, L. U.', 'Siqueira, E. M.', 'Vieira Jr, J. M.', 'Azevedo, L. C.', 'Ahmad, A. N.', 'Abu-Habsa, M.', 'Bahl, R.', 'Helme, E.', 'Hadfield, S.', 'Loveridge, R.', 'Shak, J.', 'Senver, C.', 'Howard-Griffin, R.', 'Wacharasint, P.', 'Fuengfoo, P.', 'Sukcharoen, N.', 'Rangsin, R.', 'Sbiti-Rohr, D.', 'Schuetz, P.', 'Na, H.', 'Song, S.', 'Lee, S.', 'Jeong, E.', 'Lee, K.', 'Cooper, M.', 'Milinis, K.', 'Williams, G.', 'McCarron, E.', 'Simants, S.', 'Patanwala, I.', 'Welters, I. D.', 'Zoumpelouli, E.', 'Volakli, E. 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G.', 'Swalwell, K.', 'Mandeville, J.', 'Stott, D.', 'Guerreiro, I.', 'Devine, H.', 'MacTavish, P.', 'McPeake, J.', 'Quasim, T.', 'Kinsella, J.', 'Daniel, M.', 'Goossens, C.', 'Marques, M. B.', 'Derde, S.', 'Vander Perre, S.', 'Dufour, T.', 'Thiessen, S. E.', 'Güiza, F.', 'Janssens, T.', 'Hermans, G.', 'Vanhorebeek, I.', 'De Bock, K.', 'Van den Berghe, G.', 'Langouche, L.', 'Devine, H.', 'MacTavish, P.', 'Quasim, T.', 'Kinsella, J.', 'Daniel, M.', 'McPeake, J.', 'Miles, B.', 'Madden, S.', 'Devine, H.', 'Weiler, M.', 'Marques, P.', 'Rodrigues, C.', 'Boeira, M.', 'Brenner, K.', 'Leães, C.', 'Machado, A.', 'Townsend, R.', 'Andrade, J.', 'MacTavish, P.', 'McPeake, J.', 'Devine, H.', 'Kinsella, J.', 'Daniel, M.', 'Kishore, R.', 'Fenlon, C.', 'Quasim, T.', 'Fiks, T.', 'Ruijter, A.', 'Te Raa, M.', 'Spronk, P.', 'Chiew, Y. S.', 'Docherty, P.', 'Dickson, J.', 'Moltchanova, E.', 'Scarrot, C.', 'Pretty, C.', 'Shaw, G. M.', 'Chase, J. G.', 'Hall, T.', 'Ngu, W. C.', 'Jack, J. M.', 'Morgan, P.', 'Avard, B.', 'Pavli, A.', 'Gee, X.', 'Bor, C.', 'Akin Korhan, E.', 'Demirag, K.', 'Uyar, M.', 'Shirazy, M.', 'Fayed, A.', 'Gupta, S.', 'Kaushal, A.', 'Dewan, S.', 'Varma, A.', 'Ghosh, E.', 'Yang, L.', 'Eshelman, L.', 'Lord, B.', 'Carlson, E.', 'Helme, E.', 'Broderick, R.', 'Hadfield, S.', 'Loveridge, R.', 'Ramos, J.', 'Forte, D.', 'Yang, F.', 'Hou, P.', 'Dudziak, J.', 'Feeney, J.', 'Wilkinson, K.', 'Bauchmuller, K.', 'Shuker, K.', 'Faulds, M.', 'Raithatha, A.', 'Bryden, D.', 'England, L.', 'Bolton, N.', 'Tridente, A.', 'Bauchmuller, K.', 'Shuker, K', 'Tridente, A', 'Faulds, M', 'Matheson, A', 'Gaynor, J.', 'Bryden, D', None, 'Ramos, J.', 'Peroni, B.', 'Daglius-Dias, R.', 'Miranda, L.', 'Cohen, C.', 'Carvalho, C.', 'Velasco, I.', 'Forte, D.', 'Kelly, J. M.', 'Neill, A.', 'Rubenfeld, G.', 'Masson, N.', 'Min, A.', 'Boezeman, E.', 'Hofhuis, J.', 'Hovingh, A.', 'De Vries, R.', 'Spronk, P.', 'Cabral-Campello, G.', 'Aragão, I.', 'Cardoso, T.', 'Van Mol, M.', 'Nijkamp, M.', 'Kompanje, E.', 'Ostrowski, P.', 'Omar, A.', 'Kiss, K.', 'Köves, B.', 'Csernus, V.', 'Molnár, Z.', 'Hoydonckx, Y.', 'Vanwing, S.', 'Stessel, B.', 'Van Assche, A.', 'Jamaer, L.', 'Dubois, J.', 'Medo, V.', 'Galvez, R.', 'Miranda, J. P.', 'Stone, C.', 'Wigmore, T.', 'Arunan, Y.', 'Wheeler, A.', 'Bauchmuller, K.', 'Bryden, D.', 'Wong, Y.', 'Poi, C.', 'Gu, C.', 'Molmy, P.', 'Van Grunderbeeck, N.', 'Nigeon, O.', 'Lemyze, M.', 'Thevenin, D.', 'Mallat, J.', 'Ramos, J.', 'Correa, M.', 'Carvalho, R. T.', 'Forte, D.', 'Fernandez, A.', 'McBride, C.', 'Koonthalloor, E.', 'Walsh, C.', 'Webber, A.', 'Ashe, M.', 'Smith, K.', 'Jeanrenaud, P.', 'Marudi, A.', 'Baroni, S.', 'Ragusa, F.', 'Bertellini, E.', 'Volakli, E. A.', 'Chochliourou, E.', 'Dimitriadou, M.', 'Violaki, A.', 'Mantzafleri, P.', 'Samkinidou, E.', 'Vrani, O.', 'Arbouti, A.', 'Varsami, T.', 'Sdougka, M.', 'Bollen, J. A.', 'Van Smaalen, T. C.', 'De Jongh, W. C.', 'Ten Hoopen, M. M.', 'Ysebaert, D.', 'Van Heurn, L. W.', 'Van Mook, W. N.', 'Sim, K.', 'Fuller, A.', 'Roze des Ordons, A.', 'Couillard, P.', 'Doig, C.', 'Van Keer, R. V.', 'Deschepper, R. D.', 'Francke, A. F.', 'Huyghens, L. H.', 'Bilsen, J. B.', 'Nyamaizi, B.', 'Dalrymple, C.', 'Molokhia, A.', 'Dobru, A.', 'Marrinan, E.', 'Ankuli, A.', 'Molokhia, A.', 'McPeake, J.', 'Struthers, R.', 'Crawford, R.', 'Devine, H.', 'Mactavish, P.', 'Quasim, T.', 'Morelli, P.', 'Degiovanangelo, M.', 'Lemos, F.', 'MArtinez, V.', 'Verga, F.', 'Cabrera, J.', 'Burghi, G.', 'Rutten, A.', 'Van Ieperen, S.', 'De Geer, S.', 'Van Vugt, M.', 'Der Kinderen, E.', 'Giannini, A.', 'Miccinesi, G', 'Marchesi, T', 'Prandi, E']",Crit Care,,,True
095d7495a4636ae3d259937712ce6cbb6c027f23,PMC,A green strategy for the synthesis of sulfone derivatives of p-methylaminophenol: Kinetic evaluation and antibacterial susceptibility,http://dx.doi.org/10.1038/s41598-017-04581-0,PMC5493611,28667267,CC BY,"This is one of the few examples in which the diverse products have been synthesized just by changing the applied potential. The synthesis of sulfonyl derivatives of p-methylaminophenol were carried out by reaction of the electrogenerated p-methylquinoneimine with sulfinic acids. Various types of mono (MSP), bis (BSP) and tris (TSP) sulfonyl p-methyl aminophenols were obtained by changing the electrode potential, in one pot under green conditions. The mono sulfonyl-p-(methylamino)phenol derivatives (MSP) were assessed for their in vitro antibacterial activity against the gram positive (Staphylococcus aureus) and gram negative (Escherichia coli) strains. It was found that the tested compounds were more active against Staphylococcus aureus than Escherichia coli. We also found that the antimicrobial activity of MSP derivatives to vary in the order MSP(4) (R = CH(3)) > MSP(1) (R = p-tolyl) ≈ MSP(2) (R = phenyl) > MSP(3) (R = p-ClC(6)H(4)). Moreover, the observed homogeneous rate constants (k (obs)) of the reaction of p-methyl quinoneimine with sulfinic acids were estimated in various pH values, based on the EC and ECEC mechanisms, by comparing the simulated cyclic voltammograms with the experimental ones.",2017 Jun 30,"['Nematollahi, Davood', 'Khazalpour, Sadegh', 'Ranjbar, Mina', 'Momeni, Shima']",Sci Rep,,,False
00f1ef126735474ccaf3a8d1cce9a4823d7f1228,PMC,A green strategy for the synthesis of sulfone derivatives of p-methylaminophenol: Kinetic evaluation and antibacterial susceptibility,http://dx.doi.org/10.1038/s41598-017-04581-0,PMC5493611,28667267,CC BY,"This is one of the few examples in which the diverse products have been synthesized just by changing the applied potential. The synthesis of sulfonyl derivatives of p-methylaminophenol were carried out by reaction of the electrogenerated p-methylquinoneimine with sulfinic acids. Various types of mono (MSP), bis (BSP) and tris (TSP) sulfonyl p-methyl aminophenols were obtained by changing the electrode potential, in one pot under green conditions. The mono sulfonyl-p-(methylamino)phenol derivatives (MSP) were assessed for their in vitro antibacterial activity against the gram positive (Staphylococcus aureus) and gram negative (Escherichia coli) strains. It was found that the tested compounds were more active against Staphylococcus aureus than Escherichia coli. We also found that the antimicrobial activity of MSP derivatives to vary in the order MSP(4) (R = CH(3)) > MSP(1) (R = p-tolyl) ≈ MSP(2) (R = phenyl) > MSP(3) (R = p-ClC(6)H(4)). Moreover, the observed homogeneous rate constants (k (obs)) of the reaction of p-methyl quinoneimine with sulfinic acids were estimated in various pH values, based on the EC and ECEC mechanisms, by comparing the simulated cyclic voltammograms with the experimental ones.",2017 Jun 30,"['Nematollahi, Davood', 'Khazalpour, Sadegh', 'Ranjbar, Mina', 'Momeni, Shima']",Sci Rep,,,True
2b6524fc0ce858d2db326b94ff9bf48cc14cd9a9,PMC,The C-Terminal Effector Domain of Non-Structural Protein 1 of Influenza A Virus Blocks IFN-β Production by Targeting TNF Receptor-Associated Factor 3,http://dx.doi.org/10.3389/fimmu.2017.00779,PMC5494602,28717359,CC BY,"Influenza A virus non-structural protein 1 (NS1) antagonizes interferon response through diverse strategies, particularly by inhibiting the activation of interferon regulatory factor 3 (IRF3) and IFN-β transcription. However, the underlying mechanisms used by the NS1 C-terminal effector domain (ED) to inhibit the activation of IFN-β pathway are not well understood. In this study, we used influenza virus subtype of H5N1 to demonstrate that the NS1 C-terminal ED but not the N-terminal RNA-binding domain, binds TNF receptor-associated factor 3 (TRAF3). This results in an attenuation of the type I IFN signaling pathway. We found that the NS1 C-terminal ED (named NS1/126-225) inhibits the active caspase activation and recruitment domain-containing form of RIG-I [RIG-I(N)]-induced IFN-β reporter activity, the phosphorylation of IRF3, and the induction of IFN-β. Further analysis showed that NS1/126-225 binds to TRAF3 through the TRAF domain, subsequently decreasing TRAF3 K63-linked ubiquitination. NS1/126-225 binding also disrupted the formation of the mitochondrial antiviral signaling (MAVS)–TRAF3 complex, increasing the recruitment of IKKε to MAVS; ultimately shutting down the RIG-I(N)-mediated signal transduction and cellular antiviral responses. This attenuation of cellular antiviral responses leads to evasion of the innate immune response. Taken together, our findings offer an important insight into the interplay between the influenza virus and host innate immunity.",2017 Jul 3,"['Qian, Wei', 'Wei, Xiaoqin', 'Guo, Kelei', 'Li, Yongtao', 'Lin, Xian', 'Zou, Zhong', 'Zhou, Hongbo', 'Jin, Meilin']",Front Immunol,,,True
938adb76dea182959df10403628fb8d0d697ad8b,PMC,The C-Terminal Effector Domain of Non-Structural Protein 1 of Influenza A Virus Blocks IFN-β Production by Targeting TNF Receptor-Associated Factor 3,http://dx.doi.org/10.3389/fimmu.2017.00779,PMC5494602,28717359,CC BY,"Influenza A virus non-structural protein 1 (NS1) antagonizes interferon response through diverse strategies, particularly by inhibiting the activation of interferon regulatory factor 3 (IRF3) and IFN-β transcription. However, the underlying mechanisms used by the NS1 C-terminal effector domain (ED) to inhibit the activation of IFN-β pathway are not well understood. In this study, we used influenza virus subtype of H5N1 to demonstrate that the NS1 C-terminal ED but not the N-terminal RNA-binding domain, binds TNF receptor-associated factor 3 (TRAF3). This results in an attenuation of the type I IFN signaling pathway. We found that the NS1 C-terminal ED (named NS1/126-225) inhibits the active caspase activation and recruitment domain-containing form of RIG-I [RIG-I(N)]-induced IFN-β reporter activity, the phosphorylation of IRF3, and the induction of IFN-β. Further analysis showed that NS1/126-225 binds to TRAF3 through the TRAF domain, subsequently decreasing TRAF3 K63-linked ubiquitination. NS1/126-225 binding also disrupted the formation of the mitochondrial antiviral signaling (MAVS)–TRAF3 complex, increasing the recruitment of IKKε to MAVS; ultimately shutting down the RIG-I(N)-mediated signal transduction and cellular antiviral responses. This attenuation of cellular antiviral responses leads to evasion of the innate immune response. Taken together, our findings offer an important insight into the interplay between the influenza virus and host innate immunity.",2017 Jul 3,"['Qian, Wei', 'Wei, Xiaoqin', 'Guo, Kelei', 'Li, Yongtao', 'Lin, Xian', 'Zou, Zhong', 'Zhou, Hongbo', 'Jin, Meilin']",Front Immunol,,,False
5ac2943caeef1105169bfa7240df08281b7c2733,PMC,Back to the Future: Multiparent Populations Provide the Key to Unlocking the Genetic Basis of Complex Traits,http://dx.doi.org/10.1534/genetics.117.203265,PMC5494722,28592493,CC BY,,2017 Jun 6,"['de Koning, Dirk-Jan', 'McIntyre, Lauren M.']",Genetics,,,True
a9eaa4a3217735fbc02153aeea3f34e9c763e5d3,PMC,The Severe Acute Respiratory Syndrome (SARS)-coronavirus 3a protein may function as a modulator of the trafficking properties of the spike protein,http://dx.doi.org/10.1186/1743-422X-2-5,PMC549520,15703085,CC BY,"BACKGROUND: A recent publication reported that a tyrosine-dependent sorting signal, present in cytoplasmic tail of the spike protein of most coronaviruses, mediates the intracellular retention of the spike protein. This motif is missing from the spike protein of the severe acute respiratory syndrome-coronavirus (SARS-CoV), resulting in high level of surface expression of the spike protein when it is expressed on its own in vitro. PRESENTATION OF THE HYPOTHESIS: It has been shown that the severe acute respiratory syndrome-coronavirus genome contains open reading frames that encode for proteins with no homologue in other coronaviruses. One of them is the 3a protein, which is expressed during infection in vitro and in vivo. The 3a protein, which contains a tyrosine-dependent sorting signal in its cytoplasmic domain, is expressed on the cell surface and can undergo internalization. In addition, 3a can bind to the spike protein and through this interaction, it may be able to cause the spike protein to become internalized, resulting in a decrease in its surface expression. TESTING THE HYPOTHESIS: The effects of 3a on the internalization of cell surface spike protein can be examined biochemically and the significance of the interplay between these two viral proteins during viral infection can be studied using reverse genetics methodology. IMPLICATION OF THE HYPOTHESIS: If this hypothesis is proven, it will indicate that the severe acute respiratory syndrome-coronavirus modulates the surface expression of the spike protein via a different mechanism from other coronaviruses. The interaction between 3a and S, which are expressed from separate subgenomic RNA, would be important for controlling the trafficking properties of S. The cell surface expression of S in infected cells significantly impacts viral assembly, viral spread and viral pathogenesis. Modulation by this unique pathway could confer certain advantages during the replication of the severe acute respiratory syndrome-coronavirus.",2005 Feb 10,"Tan, Yee-Joo",Virol J,,,True
222f2de4774452963b9c8b640faf80dced073b64,PMC,Reference gene selection for the shell gland of laying hens in response to time-points of eggshell formation and nicarbazin,http://dx.doi.org/10.1371/journal.pone.0180432,PMC5495395,28671969,CC BY,"Ten reference genes were investigated for normalization of gene expression data in the shell gland of laying hens. Analyses performed with geNorm revealed that hypoxanthine phosphoribosyltransferase 1 (HPRT1) and hydroxymethylbilane synthase (HMBS) were the two most stable reference genes in response to post-oviposition time alone (POT) or with nicarbazin treatment (POT+N) of laying hens. NormFinder analyses showed that the two most stable reference genes in response to POT and POT+N were 18S ribosomal RNA (18S rRNA), ribosomal protein L4 (RPL4) and HMBS, RPL4, respectively. BestKeeper analyses showed that 18S rRNA, RPL4 and HPRT1, HMBS were the two most stable reference genes for POT, and POT+N, respectively. Of the ten reference genes, all except B2M showed geNorm M <0.5, suggesting that they were stably expressed in the shell gland tissue. Consensus from these three programs suggested HPRT1 and HMBS could be used as the two most stable reference genes in the present study. Expression analyses of four candidate target genes with the two most and the two least stable genes showed that a combination of stable reference genes leads to more discriminable quantification of expression levels of target genes, while the least stable genes failed to do so. Therefore, HMBS and HPRT1 are recommended as the two most stable reference genes for the normalization of gene expression data at different stages of eggshell formation in brown-egg laying hens. Available statistical programs for reference gene ranking should include more robust analysis capability to analyse the gene expression data generated from factorial design experiments.",2017 Jul 3,"['Samiullah, Sami', 'Roberts, Juliet', 'Wu, Shu-Biao']",PLoS One,,,True
65cc7496f21429d81b3ae129d9c39764e2a1f568,PMC,The Courage to Change the Rules: A Proposal for an Essential Health R&D Treaty,http://dx.doi.org/10.1371/journal.pmed.0020014,PMC549583,15736991,CC BY,The medical needs of many of the world's population go unmet. A new treaty on essential health R&D could provide a binding framework to redirect today's scientific expertise to priority needs,2005 Feb 22,"['Dentico, Nicoletta', 'Ford, Nathan']",PLoS Med,,,True
38fec468e30f4e956339345baeef4f15c7541cf5,PMC,SARS Transmission Pattern in Singapore Reassessed by Viral Sequence Variation Analysis,http://dx.doi.org/10.1371/journal.pmed.0020043,PMC549591,15736999,CC BY,"BACKGROUND: Epidemiological investigations of infectious disease are mainly dependent on indirect contact information and only occasionally assisted by characterization of pathogen sequence variation from clinical isolates. Direct sequence analysis of the pathogen, particularly at a population level, is generally thought to be too cumbersome, technically difficult, and expensive. We present here a novel application of mass spectrometry (MS)–based technology in characterizing viral sequence variations that overcomes these problems, and we apply it retrospectively to the severe acute respiratory syndrome (SARS) outbreak in Singapore. METHODS AND FINDINGS: The success rate of the MS-based analysis for detecting SARS coronavirus (SARS-CoV) sequence variations was determined to be 95% with 75 copies of viral RNA per reaction, which is sufficient to directly analyze both clinical and cultured samples. Analysis of 13 SARS-CoV isolates from the different stages of the Singapore outbreak identified nine sequence variations that could define the molecular relationship between them and pointed to a new, previously unidentified, primary route of introduction of SARS-CoV into the Singapore population. Our direct determination of viral sequence variation from a clinical sample also clarified an unresolved epidemiological link regarding the acquisition of SARS in a German patient. We were also able to detect heterogeneous viral sequences in primary lung tissues, suggesting a possible coevolution of quasispecies of virus within a single host. CONCLUSION: This study has further demonstrated the importance of improving clinical and epidemiological studies of pathogen transmission through the use of genetic analysis and has revealed the MS-based analysis to be a sensitive and accurate method for characterizing SARS-CoV genetic variations in clinical samples. We suggest that this approach should be used routinely during outbreaks of a wide variety of agents, in order to allow the most effective control.",2005 Feb 22,"['Liu, Jianjun', 'Lim, Siew Lan', 'Ruan, Yijun', 'Ling, Ai Ee', 'Ng, Lisa F. P', 'Drosten, Christian', 'Liu, Edison T', 'Stanton, Lawrence W', 'Hibberd, Martin L']",PLoS Med,,,True
3e84209d746b9da073a072f3c5396ef27a6a2cd9,PMC,Mass Spectometry–Based SARS Genotyping,http://dx.doi.org/10.1371/journal.pmed.0020052,PMC549598,,CC BY,,2005 Feb 22,,PLoS Med,,,False
1185a17f1cb650e0433ab8c84202cc242c54f6cc,PMC,Cost-effectiveness analysis of N95 respirators and medical masks to protect healthcare workers in China from respiratory infections,http://dx.doi.org/10.1186/s12879-017-2564-9,PMC5496227,28673259,CC BY,"BACKGROUND: There are substantial differences between the costs of medical masks and N95 respirators. Cost-effectiveness analysis is required to assist decision-makers evaluating alternative healthcare worker (HCW) mask/respirator strategies. This study aims to compare the cost-effectiveness of N95 respirators and medical masks for protecting HCWs in Beijing, China. METHODS: We developed a cost-effectiveness analysis model utilising efficacy and resource use data from two cluster randomised clinical trials assessing various mask/respirator strategies conducted in HCWs in Level 2 and 3 Beijing hospitals for the 2008–09 and 2009–10 influenza seasons. The main outcome measure was the incremental cost-effectiveness ratio (ICER) per clinical respiratory illness (CRI) case prevented. We used a societal perspective which included intervention costs, the healthcare costs of CRI in HCWs and absenteeism costs. RESULTS: The incremental cost to prevent a CRI case with continuous use of N95 respirators when compared to medical masks ranged from US $490–$1230 (approx. 3000-7600 RMB). One-way sensitivity analysis indicated that the CRI attack rate and intervention effectiveness had the greatest impact on cost-effectiveness. CONCLUSIONS: The determination of cost-effectiveness for mask/respirator strategies will depend on the willingness to pay to prevent a CRI case in a HCW, which will vary between countries. In the case of a highly pathogenic pandemic, respirator use in HCWs would likely be a cost-effective intervention.",2017 Jul 3,"['Mukerji, Shohini', 'MacIntyre, C. Raina', 'Seale, Holly', 'Wang, Quanyi', 'Yang, Peng', 'Wang, Xiaoli', 'Newall, Anthony T.']",BMC Infect Dis,,,True
188337e43aa524493372f8769b6bac8b366850ca,PMC,Cynanchum wilfordii Polysaccharides Suppress Dextran Sulfate Sodium-Induced Acute Colitis in Mice and the Production of Inflammatory Mediators from Macrophages,http://dx.doi.org/10.1155/2017/3859856,PMC5496321,28751820,CC BY,"We recently reported the immune-enhancing effects of a high-molecular-weight fraction (HMF) of CW in macrophages and immunosuppressed mice, and this effect was attributed to a crude polysaccharide. As polysaccharides may also have anti-inflammatory functions, we investigated the anti-inflammatory effects and related molecular mechanisms of a crude polysaccharide (HMFO) obtained from HMF of CW in mice with dextran sulfate sodium- (DSS-) induced colitis and in lipopolysaccharide-induced RAW 264.7 macrophages. HMFO ameliorated the pathological characteristics of colitis and significantly reduced production of proinflammatory cytokines in the serum. Histological analysis indicated that HMFO improved the signs of histological damage such as abnormal crypts, crypt loss, and inflammatory cell infiltration induced by DSS. In addition, HMFO inhibited iNOS and COX-2 protein expression, as well as phosphorylated NF-κB p65 levels in the colon tissue of mice with DSS-induced colitis. In macrophages, HMFO inhibited several cytokines and enzymes involved in inflammation such as prostaglandin E(2), nitric oxide, tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 by attenuating nuclear factor-κB (NF-κB) and mitogen-activated protein kinases. HMFO attenuated inflammation both in vitro and in vivo, primarily by inhibiting NF-κB activation. Our findings indicate that HMFO is a promising remedy for treating inflammatory bowel diseases, such as colitis.",2017 Jun 20,"['Cho, Chang-Won', 'Ahn, Sungeun', 'Lim, Tae-Gyu', 'Hong, Hee-Do', 'Rhee, Young Kyoung', 'Yang, Deok-Chun', 'Jang, Mi']",Mediators Inflamm,,,True
5b13c9552c2cf5956633dff2463ab0f274d93708,PMC,"Recent increase of surface particulate matter concentrations in the Seoul Metropolitan Area, Korea",http://dx.doi.org/10.1038/s41598-017-05092-8,PMC5498658,28680054,CC BY,"Recent changes of surface particulate matter (PM) concentration in the Seoul Metropolitan Area (SMA), South Korea, are puzzling. The long-term trend of surface PM concentration in the SMA declined in the 2000s, but since 2012 its concentrations have tended to incline, which is coincident with frequent severe hazes in South Korea. This increase puts the Korean government’s emission reduction efforts in jeopardy. This study reports that interannual variation of surface PM concentration in South Korea is closely linked with the interannual variations of wind speed. A 12-year (2004–2015) regional air quality simulation was conducted over East Asia (27-km) and over South Korea (9-km) to assess the impact of meteorology under constant anthropogenic emissions. Simulated PM concentrations show a strong negative correlation (i.e. R = −0.86) with regional wind speed, implying that reduced regional ventilation is likely associated with more stagnant conditions that cause severe pollutant episodes in South Korea. We conclude that the current PM concentration trend in South Korea is a combination of long-term decline by emission control efforts and short-term fluctuation of regional wind speed interannual variability. When the meteorology-driven variations are removed, PM concentrations in South Korea have declined continuously even after 2012.",2017 Jul 5,"['Kim, Hyun Cheol', 'Kim, Soontae', 'Kim, Byeong-Uk', 'Jin, Chun-Sil', 'Hong, Songyou', 'Park, Rokjin', 'Son, Seok-Woo', 'Bae, Changhan', 'Bae, MinAh', 'Song, Chang-Keun', 'Stein, Ariel']",Sci Rep,,,True
602e006ebff0a1b81a8d922ce9504421f218bfb7,PMC,"Interrelationship between Climatic, Ecologic, Social, and Cultural Determinants Affecting Dengue Emergence and Transmission in Puerto Rico and Their Implications for Zika Response",http://dx.doi.org/10.1155/2017/8947067,PMC5498925,28717366,CC BY,"OBJECTIVE: The global resurgence of dengue has been attributed to rapid population growth, urban expansion, increased air travel, globalization, and climate change. Dengue is now endemic in Puerto Rico. Puerto Rico is at risk for Zika, another emerging arbovirus. The interrelationship between climatic, ecological, social, and cultural factors that affect dengue and other arboviruses' transmission is understudied. DESIGN: The objective of this systematic review is to examine the interrelationship between climatic, ecological, social, and cultural factors on dengue transmission in Puerto Rico and to draw lessons for Zika response. RESULTS: A comprehensive search of peer-reviewed journal articles was performed, producing 562 articles; 26 were selected for this review. Findings indicate that human activities and behaviors (urbanization, migration, and consumption) as well as climate have a significant impact on the abundance and the transmission potential of Ae. aegypti, the vector for dengue, Zika, and other viruses. CONCLUSION: Despite the public health burden of dengue limited investments have been made in research and surveillance. Future research is needed to develop models that integrate the multivariate effects of climatic, ecological, social, and cultural factors, which for Puerto Rico have mostly been examined independently. Such models have the potential to inform response to dengue, Zika, and other arboviruses.",2017 Jun 22,"['Matysiak, Angela', 'Roess, Amira']",J Trop Med,,,True
103bb334655ed9629d91f182758f51a5002f2948,PMC,Genomes of the Mouse Collaborative Cross,http://dx.doi.org/10.1534/genetics.116.198838,PMC5499171,28592495,CC BY,"The Collaborative Cross (CC) is a multiparent panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because of their long-term genetic stability, which enhances reproducibility and integration of data collected across time and conditions. Characterization of their genomes can be a community effort, reducing the burden on individual users. Here we present the genomes of the CC strains using two complementary approaches as a resource to improve power and interpretation of genetic experiments. Our study also provides a cautionary tale regarding the limitations imposed by such basic biological processes as mutation and selection. A distinct advantage of inbred panels is that genotyping only needs to be performed on the panel, not on each individual mouse. The initial CC genome data were haplotype reconstructions based on dense genotyping of the most recent common ancestors (MRCAs) of each strain followed by imputation from the genome sequence of the corresponding founder inbred strain. The MRCA resource captured segregating regions in strains that were not fully inbred, but it had limited resolution in the transition regions between founder haplotypes, and there was uncertainty about founder assignment in regions of limited diversity. Here we report the whole genome sequence of 69 CC strains generated by paired-end short reads at 30× coverage of a single male per strain. Sequencing leads to a substantial improvement in the fine structure and completeness of the genomes of the CC. Both MRCAs and sequenced samples show a significant reduction in the genome-wide haplotype frequencies from two wild-derived strains, CAST/EiJ and PWK/PhJ. In addition, analysis of the evolution of the patterns of heterozygosity indicates that selection against three wild-derived founder strains played a significant role in shaping the genomes of the CC. The sequencing resource provides the first description of tens of thousands of new genetic variants introduced by mutation and drift in the CC genomes. We estimate that new SNP mutations are accumulating in each CC strain at a rate of 2.4 ± 0.4 per gigabase per generation. The fixation of new mutations by genetic drift has introduced thousands of new variants into the CC strains. The majority of these mutations are novel compared to currently sequenced laboratory stocks and wild mice, and some are predicted to alter gene function. Approximately one-third of the CC inbred strains have acquired large deletions (>10 kb) many of which overlap known coding genes and functional elements. The sequence of these mice is a critical resource to CC users, increases threefold the number of mouse inbred strain genomes available publicly, and provides insight into the effect of mutation and drift on common resources.",2017 Jun 6,"['Srivastava, Anuj', 'Morgan, Andrew P.', 'Najarian, Maya L.', 'Sarsani, Vishal Kumar', 'Sigmon, J. Sebastian', 'Shorter, John R.', 'Kashfeen, Anwica', 'McMullan, Rachel C.', 'Williams, Lucy H.', 'Giusti-Rodríguez, Paola', 'Ferris, Martin T.', 'Sullivan, Patrick', 'Hock, Pablo', 'Miller, Darla R.', 'Bell, Timothy A.', 'McMillan, Leonard', 'Churchill, Gary A.', 'de Villena, Fernando Pardo-Manuel']",Genetics,,,False
407d9f523fbb2c320f584064fe369eb424d9e664,PMC,Genomes of the Mouse Collaborative Cross,http://dx.doi.org/10.1534/genetics.116.198838,PMC5499171,28592495,CC BY,"The Collaborative Cross (CC) is a multiparent panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because of their long-term genetic stability, which enhances reproducibility and integration of data collected across time and conditions. Characterization of their genomes can be a community effort, reducing the burden on individual users. Here we present the genomes of the CC strains using two complementary approaches as a resource to improve power and interpretation of genetic experiments. Our study also provides a cautionary tale regarding the limitations imposed by such basic biological processes as mutation and selection. A distinct advantage of inbred panels is that genotyping only needs to be performed on the panel, not on each individual mouse. The initial CC genome data were haplotype reconstructions based on dense genotyping of the most recent common ancestors (MRCAs) of each strain followed by imputation from the genome sequence of the corresponding founder inbred strain. The MRCA resource captured segregating regions in strains that were not fully inbred, but it had limited resolution in the transition regions between founder haplotypes, and there was uncertainty about founder assignment in regions of limited diversity. Here we report the whole genome sequence of 69 CC strains generated by paired-end short reads at 30× coverage of a single male per strain. Sequencing leads to a substantial improvement in the fine structure and completeness of the genomes of the CC. Both MRCAs and sequenced samples show a significant reduction in the genome-wide haplotype frequencies from two wild-derived strains, CAST/EiJ and PWK/PhJ. In addition, analysis of the evolution of the patterns of heterozygosity indicates that selection against three wild-derived founder strains played a significant role in shaping the genomes of the CC. The sequencing resource provides the first description of tens of thousands of new genetic variants introduced by mutation and drift in the CC genomes. We estimate that new SNP mutations are accumulating in each CC strain at a rate of 2.4 ± 0.4 per gigabase per generation. The fixation of new mutations by genetic drift has introduced thousands of new variants into the CC strains. The majority of these mutations are novel compared to currently sequenced laboratory stocks and wild mice, and some are predicted to alter gene function. Approximately one-third of the CC inbred strains have acquired large deletions (>10 kb) many of which overlap known coding genes and functional elements. The sequence of these mice is a critical resource to CC users, increases threefold the number of mouse inbred strain genomes available publicly, and provides insight into the effect of mutation and drift on common resources.",2017 Jun 6,"['Srivastava, Anuj', 'Morgan, Andrew P.', 'Najarian, Maya L.', 'Sarsani, Vishal Kumar', 'Sigmon, J. Sebastian', 'Shorter, John R.', 'Kashfeen, Anwica', 'McMullan, Rachel C.', 'Williams, Lucy H.', 'Giusti-Rodríguez, Paola', 'Ferris, Martin T.', 'Sullivan, Patrick', 'Hock, Pablo', 'Miller, Darla R.', 'Bell, Timothy A.', 'McMillan, Leonard', 'Churchill, Gary A.', 'de Villena, Fernando Pardo-Manuel']",Genetics,,,False
99f65cc35f9d389689d702a857707aad8a095cfe,PMC,Genomes of the Mouse Collaborative Cross,http://dx.doi.org/10.1534/genetics.116.198838,PMC5499171,28592495,CC BY,"The Collaborative Cross (CC) is a multiparent panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because of their long-term genetic stability, which enhances reproducibility and integration of data collected across time and conditions. Characterization of their genomes can be a community effort, reducing the burden on individual users. Here we present the genomes of the CC strains using two complementary approaches as a resource to improve power and interpretation of genetic experiments. Our study also provides a cautionary tale regarding the limitations imposed by such basic biological processes as mutation and selection. A distinct advantage of inbred panels is that genotyping only needs to be performed on the panel, not on each individual mouse. The initial CC genome data were haplotype reconstructions based on dense genotyping of the most recent common ancestors (MRCAs) of each strain followed by imputation from the genome sequence of the corresponding founder inbred strain. The MRCA resource captured segregating regions in strains that were not fully inbred, but it had limited resolution in the transition regions between founder haplotypes, and there was uncertainty about founder assignment in regions of limited diversity. Here we report the whole genome sequence of 69 CC strains generated by paired-end short reads at 30× coverage of a single male per strain. Sequencing leads to a substantial improvement in the fine structure and completeness of the genomes of the CC. Both MRCAs and sequenced samples show a significant reduction in the genome-wide haplotype frequencies from two wild-derived strains, CAST/EiJ and PWK/PhJ. In addition, analysis of the evolution of the patterns of heterozygosity indicates that selection against three wild-derived founder strains played a significant role in shaping the genomes of the CC. The sequencing resource provides the first description of tens of thousands of new genetic variants introduced by mutation and drift in the CC genomes. We estimate that new SNP mutations are accumulating in each CC strain at a rate of 2.4 ± 0.4 per gigabase per generation. The fixation of new mutations by genetic drift has introduced thousands of new variants into the CC strains. The majority of these mutations are novel compared to currently sequenced laboratory stocks and wild mice, and some are predicted to alter gene function. Approximately one-third of the CC inbred strains have acquired large deletions (>10 kb) many of which overlap known coding genes and functional elements. The sequence of these mice is a critical resource to CC users, increases threefold the number of mouse inbred strain genomes available publicly, and provides insight into the effect of mutation and drift on common resources.",2017 Jun 6,"['Srivastava, Anuj', 'Morgan, Andrew P.', 'Najarian, Maya L.', 'Sarsani, Vishal Kumar', 'Sigmon, J. Sebastian', 'Shorter, John R.', 'Kashfeen, Anwica', 'McMullan, Rachel C.', 'Williams, Lucy H.', 'Giusti-Rodríguez, Paola', 'Ferris, Martin T.', 'Sullivan, Patrick', 'Hock, Pablo', 'Miller, Darla R.', 'Bell, Timothy A.', 'McMillan, Leonard', 'Churchill, Gary A.', 'de Villena, Fernando Pardo-Manuel']",Genetics,,,False
7cf06eaa3245081fa84a74a5171810e05baf2d7a,PMC,Genomes of the Mouse Collaborative Cross,http://dx.doi.org/10.1534/genetics.116.198838,PMC5499171,28592495,CC BY,"The Collaborative Cross (CC) is a multiparent panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because of their long-term genetic stability, which enhances reproducibility and integration of data collected across time and conditions. Characterization of their genomes can be a community effort, reducing the burden on individual users. Here we present the genomes of the CC strains using two complementary approaches as a resource to improve power and interpretation of genetic experiments. Our study also provides a cautionary tale regarding the limitations imposed by such basic biological processes as mutation and selection. A distinct advantage of inbred panels is that genotyping only needs to be performed on the panel, not on each individual mouse. The initial CC genome data were haplotype reconstructions based on dense genotyping of the most recent common ancestors (MRCAs) of each strain followed by imputation from the genome sequence of the corresponding founder inbred strain. The MRCA resource captured segregating regions in strains that were not fully inbred, but it had limited resolution in the transition regions between founder haplotypes, and there was uncertainty about founder assignment in regions of limited diversity. Here we report the whole genome sequence of 69 CC strains generated by paired-end short reads at 30× coverage of a single male per strain. Sequencing leads to a substantial improvement in the fine structure and completeness of the genomes of the CC. Both MRCAs and sequenced samples show a significant reduction in the genome-wide haplotype frequencies from two wild-derived strains, CAST/EiJ and PWK/PhJ. In addition, analysis of the evolution of the patterns of heterozygosity indicates that selection against three wild-derived founder strains played a significant role in shaping the genomes of the CC. The sequencing resource provides the first description of tens of thousands of new genetic variants introduced by mutation and drift in the CC genomes. We estimate that new SNP mutations are accumulating in each CC strain at a rate of 2.4 ± 0.4 per gigabase per generation. The fixation of new mutations by genetic drift has introduced thousands of new variants into the CC strains. The majority of these mutations are novel compared to currently sequenced laboratory stocks and wild mice, and some are predicted to alter gene function. Approximately one-third of the CC inbred strains have acquired large deletions (>10 kb) many of which overlap known coding genes and functional elements. The sequence of these mice is a critical resource to CC users, increases threefold the number of mouse inbred strain genomes available publicly, and provides insight into the effect of mutation and drift on common resources.",2017 Jun 6,"['Srivastava, Anuj', 'Morgan, Andrew P.', 'Najarian, Maya L.', 'Sarsani, Vishal Kumar', 'Sigmon, J. Sebastian', 'Shorter, John R.', 'Kashfeen, Anwica', 'McMullan, Rachel C.', 'Williams, Lucy H.', 'Giusti-Rodríguez, Paola', 'Ferris, Martin T.', 'Sullivan, Patrick', 'Hock, Pablo', 'Miller, Darla R.', 'Bell, Timothy A.', 'McMillan, Leonard', 'Churchill, Gary A.', 'de Villena, Fernando Pardo-Manuel']",Genetics,,,False
7a407bd0afc0d6d22213e7cc44c0b82a5ba2b929,PMC,Genomes of the Mouse Collaborative Cross,http://dx.doi.org/10.1534/genetics.116.198838,PMC5499171,28592495,CC BY,"The Collaborative Cross (CC) is a multiparent panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because of their long-term genetic stability, which enhances reproducibility and integration of data collected across time and conditions. Characterization of their genomes can be a community effort, reducing the burden on individual users. Here we present the genomes of the CC strains using two complementary approaches as a resource to improve power and interpretation of genetic experiments. Our study also provides a cautionary tale regarding the limitations imposed by such basic biological processes as mutation and selection. A distinct advantage of inbred panels is that genotyping only needs to be performed on the panel, not on each individual mouse. The initial CC genome data were haplotype reconstructions based on dense genotyping of the most recent common ancestors (MRCAs) of each strain followed by imputation from the genome sequence of the corresponding founder inbred strain. The MRCA resource captured segregating regions in strains that were not fully inbred, but it had limited resolution in the transition regions between founder haplotypes, and there was uncertainty about founder assignment in regions of limited diversity. Here we report the whole genome sequence of 69 CC strains generated by paired-end short reads at 30× coverage of a single male per strain. Sequencing leads to a substantial improvement in the fine structure and completeness of the genomes of the CC. Both MRCAs and sequenced samples show a significant reduction in the genome-wide haplotype frequencies from two wild-derived strains, CAST/EiJ and PWK/PhJ. In addition, analysis of the evolution of the patterns of heterozygosity indicates that selection against three wild-derived founder strains played a significant role in shaping the genomes of the CC. The sequencing resource provides the first description of tens of thousands of new genetic variants introduced by mutation and drift in the CC genomes. We estimate that new SNP mutations are accumulating in each CC strain at a rate of 2.4 ± 0.4 per gigabase per generation. The fixation of new mutations by genetic drift has introduced thousands of new variants into the CC strains. The majority of these mutations are novel compared to currently sequenced laboratory stocks and wild mice, and some are predicted to alter gene function. Approximately one-third of the CC inbred strains have acquired large deletions (>10 kb) many of which overlap known coding genes and functional elements. The sequence of these mice is a critical resource to CC users, increases threefold the number of mouse inbred strain genomes available publicly, and provides insight into the effect of mutation and drift on common resources.",2017 Jun 6,"['Srivastava, Anuj', 'Morgan, Andrew P.', 'Najarian, Maya L.', 'Sarsani, Vishal Kumar', 'Sigmon, J. Sebastian', 'Shorter, John R.', 'Kashfeen, Anwica', 'McMullan, Rachel C.', 'Williams, Lucy H.', 'Giusti-Rodríguez, Paola', 'Ferris, Martin T.', 'Sullivan, Patrick', 'Hock, Pablo', 'Miller, Darla R.', 'Bell, Timothy A.', 'McMillan, Leonard', 'Churchill, Gary A.', 'de Villena, Fernando Pardo-Manuel']",Genetics,,,False
21d854755ecbf2260203c614ae5036a045d6106c,PMC,Genomes of the Mouse Collaborative Cross,http://dx.doi.org/10.1534/genetics.116.198838,PMC5499171,28592495,CC BY,"The Collaborative Cross (CC) is a multiparent panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because of their long-term genetic stability, which enhances reproducibility and integration of data collected across time and conditions. Characterization of their genomes can be a community effort, reducing the burden on individual users. Here we present the genomes of the CC strains using two complementary approaches as a resource to improve power and interpretation of genetic experiments. Our study also provides a cautionary tale regarding the limitations imposed by such basic biological processes as mutation and selection. A distinct advantage of inbred panels is that genotyping only needs to be performed on the panel, not on each individual mouse. The initial CC genome data were haplotype reconstructions based on dense genotyping of the most recent common ancestors (MRCAs) of each strain followed by imputation from the genome sequence of the corresponding founder inbred strain. The MRCA resource captured segregating regions in strains that were not fully inbred, but it had limited resolution in the transition regions between founder haplotypes, and there was uncertainty about founder assignment in regions of limited diversity. Here we report the whole genome sequence of 69 CC strains generated by paired-end short reads at 30× coverage of a single male per strain. Sequencing leads to a substantial improvement in the fine structure and completeness of the genomes of the CC. Both MRCAs and sequenced samples show a significant reduction in the genome-wide haplotype frequencies from two wild-derived strains, CAST/EiJ and PWK/PhJ. In addition, analysis of the evolution of the patterns of heterozygosity indicates that selection against three wild-derived founder strains played a significant role in shaping the genomes of the CC. The sequencing resource provides the first description of tens of thousands of new genetic variants introduced by mutation and drift in the CC genomes. We estimate that new SNP mutations are accumulating in each CC strain at a rate of 2.4 ± 0.4 per gigabase per generation. The fixation of new mutations by genetic drift has introduced thousands of new variants into the CC strains. The majority of these mutations are novel compared to currently sequenced laboratory stocks and wild mice, and some are predicted to alter gene function. Approximately one-third of the CC inbred strains have acquired large deletions (>10 kb) many of which overlap known coding genes and functional elements. The sequence of these mice is a critical resource to CC users, increases threefold the number of mouse inbred strain genomes available publicly, and provides insight into the effect of mutation and drift on common resources.",2017 Jun 6,"['Srivastava, Anuj', 'Morgan, Andrew P.', 'Najarian, Maya L.', 'Sarsani, Vishal Kumar', 'Sigmon, J. Sebastian', 'Shorter, John R.', 'Kashfeen, Anwica', 'McMullan, Rachel C.', 'Williams, Lucy H.', 'Giusti-Rodríguez, Paola', 'Ferris, Martin T.', 'Sullivan, Patrick', 'Hock, Pablo', 'Miller, Darla R.', 'Bell, Timothy A.', 'McMillan, Leonard', 'Churchill, Gary A.', 'de Villena, Fernando Pardo-Manuel']",Genetics,,,False
51649081f341652e81b112820fec01b8104c9584,PMC,Genomes of the Mouse Collaborative Cross,http://dx.doi.org/10.1534/genetics.116.198838,PMC5499171,28592495,CC BY,"The Collaborative Cross (CC) is a multiparent panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because of their long-term genetic stability, which enhances reproducibility and integration of data collected across time and conditions. Characterization of their genomes can be a community effort, reducing the burden on individual users. Here we present the genomes of the CC strains using two complementary approaches as a resource to improve power and interpretation of genetic experiments. Our study also provides a cautionary tale regarding the limitations imposed by such basic biological processes as mutation and selection. A distinct advantage of inbred panels is that genotyping only needs to be performed on the panel, not on each individual mouse. The initial CC genome data were haplotype reconstructions based on dense genotyping of the most recent common ancestors (MRCAs) of each strain followed by imputation from the genome sequence of the corresponding founder inbred strain. The MRCA resource captured segregating regions in strains that were not fully inbred, but it had limited resolution in the transition regions between founder haplotypes, and there was uncertainty about founder assignment in regions of limited diversity. Here we report the whole genome sequence of 69 CC strains generated by paired-end short reads at 30× coverage of a single male per strain. Sequencing leads to a substantial improvement in the fine structure and completeness of the genomes of the CC. Both MRCAs and sequenced samples show a significant reduction in the genome-wide haplotype frequencies from two wild-derived strains, CAST/EiJ and PWK/PhJ. In addition, analysis of the evolution of the patterns of heterozygosity indicates that selection against three wild-derived founder strains played a significant role in shaping the genomes of the CC. The sequencing resource provides the first description of tens of thousands of new genetic variants introduced by mutation and drift in the CC genomes. We estimate that new SNP mutations are accumulating in each CC strain at a rate of 2.4 ± 0.4 per gigabase per generation. The fixation of new mutations by genetic drift has introduced thousands of new variants into the CC strains. The majority of these mutations are novel compared to currently sequenced laboratory stocks and wild mice, and some are predicted to alter gene function. Approximately one-third of the CC inbred strains have acquired large deletions (>10 kb) many of which overlap known coding genes and functional elements. The sequence of these mice is a critical resource to CC users, increases threefold the number of mouse inbred strain genomes available publicly, and provides insight into the effect of mutation and drift on common resources.",2017 Jun 6,"['Srivastava, Anuj', 'Morgan, Andrew P.', 'Najarian, Maya L.', 'Sarsani, Vishal Kumar', 'Sigmon, J. Sebastian', 'Shorter, John R.', 'Kashfeen, Anwica', 'McMullan, Rachel C.', 'Williams, Lucy H.', 'Giusti-Rodríguez, Paola', 'Ferris, Martin T.', 'Sullivan, Patrick', 'Hock, Pablo', 'Miller, Darla R.', 'Bell, Timothy A.', 'McMillan, Leonard', 'Churchill, Gary A.', 'de Villena, Fernando Pardo-Manuel']",Genetics,,,False
4a57e7e0fe22fe11dec70a16eeca888935422844,PMC,Genomes of the Mouse Collaborative Cross,http://dx.doi.org/10.1534/genetics.116.198838,PMC5499171,28592495,CC BY,"The Collaborative Cross (CC) is a multiparent panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because of their long-term genetic stability, which enhances reproducibility and integration of data collected across time and conditions. Characterization of their genomes can be a community effort, reducing the burden on individual users. Here we present the genomes of the CC strains using two complementary approaches as a resource to improve power and interpretation of genetic experiments. Our study also provides a cautionary tale regarding the limitations imposed by such basic biological processes as mutation and selection. A distinct advantage of inbred panels is that genotyping only needs to be performed on the panel, not on each individual mouse. The initial CC genome data were haplotype reconstructions based on dense genotyping of the most recent common ancestors (MRCAs) of each strain followed by imputation from the genome sequence of the corresponding founder inbred strain. The MRCA resource captured segregating regions in strains that were not fully inbred, but it had limited resolution in the transition regions between founder haplotypes, and there was uncertainty about founder assignment in regions of limited diversity. Here we report the whole genome sequence of 69 CC strains generated by paired-end short reads at 30× coverage of a single male per strain. Sequencing leads to a substantial improvement in the fine structure and completeness of the genomes of the CC. Both MRCAs and sequenced samples show a significant reduction in the genome-wide haplotype frequencies from two wild-derived strains, CAST/EiJ and PWK/PhJ. In addition, analysis of the evolution of the patterns of heterozygosity indicates that selection against three wild-derived founder strains played a significant role in shaping the genomes of the CC. The sequencing resource provides the first description of tens of thousands of new genetic variants introduced by mutation and drift in the CC genomes. We estimate that new SNP mutations are accumulating in each CC strain at a rate of 2.4 ± 0.4 per gigabase per generation. The fixation of new mutations by genetic drift has introduced thousands of new variants into the CC strains. The majority of these mutations are novel compared to currently sequenced laboratory stocks and wild mice, and some are predicted to alter gene function. Approximately one-third of the CC inbred strains have acquired large deletions (>10 kb) many of which overlap known coding genes and functional elements. The sequence of these mice is a critical resource to CC users, increases threefold the number of mouse inbred strain genomes available publicly, and provides insight into the effect of mutation and drift on common resources.",2017 Jun 6,"['Srivastava, Anuj', 'Morgan, Andrew P.', 'Najarian, Maya L.', 'Sarsani, Vishal Kumar', 'Sigmon, J. Sebastian', 'Shorter, John R.', 'Kashfeen, Anwica', 'McMullan, Rachel C.', 'Williams, Lucy H.', 'Giusti-Rodríguez, Paola', 'Ferris, Martin T.', 'Sullivan, Patrick', 'Hock, Pablo', 'Miller, Darla R.', 'Bell, Timothy A.', 'McMillan, Leonard', 'Churchill, Gary A.', 'de Villena, Fernando Pardo-Manuel']",Genetics,,,False
eef4cc12b84be0a4217da828b75f06529ba5d01b,PMC,Genomes of the Mouse Collaborative Cross,http://dx.doi.org/10.1534/genetics.116.198838,PMC5499171,28592495,CC BY,"The Collaborative Cross (CC) is a multiparent panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because of their long-term genetic stability, which enhances reproducibility and integration of data collected across time and conditions. Characterization of their genomes can be a community effort, reducing the burden on individual users. Here we present the genomes of the CC strains using two complementary approaches as a resource to improve power and interpretation of genetic experiments. Our study also provides a cautionary tale regarding the limitations imposed by such basic biological processes as mutation and selection. A distinct advantage of inbred panels is that genotyping only needs to be performed on the panel, not on each individual mouse. The initial CC genome data were haplotype reconstructions based on dense genotyping of the most recent common ancestors (MRCAs) of each strain followed by imputation from the genome sequence of the corresponding founder inbred strain. The MRCA resource captured segregating regions in strains that were not fully inbred, but it had limited resolution in the transition regions between founder haplotypes, and there was uncertainty about founder assignment in regions of limited diversity. Here we report the whole genome sequence of 69 CC strains generated by paired-end short reads at 30× coverage of a single male per strain. Sequencing leads to a substantial improvement in the fine structure and completeness of the genomes of the CC. Both MRCAs and sequenced samples show a significant reduction in the genome-wide haplotype frequencies from two wild-derived strains, CAST/EiJ and PWK/PhJ. In addition, analysis of the evolution of the patterns of heterozygosity indicates that selection against three wild-derived founder strains played a significant role in shaping the genomes of the CC. The sequencing resource provides the first description of tens of thousands of new genetic variants introduced by mutation and drift in the CC genomes. We estimate that new SNP mutations are accumulating in each CC strain at a rate of 2.4 ± 0.4 per gigabase per generation. The fixation of new mutations by genetic drift has introduced thousands of new variants into the CC strains. The majority of these mutations are novel compared to currently sequenced laboratory stocks and wild mice, and some are predicted to alter gene function. Approximately one-third of the CC inbred strains have acquired large deletions (>10 kb) many of which overlap known coding genes and functional elements. The sequence of these mice is a critical resource to CC users, increases threefold the number of mouse inbred strain genomes available publicly, and provides insight into the effect of mutation and drift on common resources.",2017 Jun 6,"['Srivastava, Anuj', 'Morgan, Andrew P.', 'Najarian, Maya L.', 'Sarsani, Vishal Kumar', 'Sigmon, J. Sebastian', 'Shorter, John R.', 'Kashfeen, Anwica', 'McMullan, Rachel C.', 'Williams, Lucy H.', 'Giusti-Rodríguez, Paola', 'Ferris, Martin T.', 'Sullivan, Patrick', 'Hock, Pablo', 'Miller, Darla R.', 'Bell, Timothy A.', 'McMillan, Leonard', 'Churchill, Gary A.', 'de Villena, Fernando Pardo-Manuel']",Genetics,,,True
7d25d7686c679f9f1e1f04a605f6bbaa385435ea,PMC,Crystal structure of Middle East respiratory syndrome coronavirus helicase,http://dx.doi.org/10.1371/journal.ppat.1006474,PMC5501694,28651017,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) remains a threat to public health worldwide; however, effective vaccine or drug against CoVs remains unavailable. CoV helicase is one of the three evolutionary most conserved proteins in nidoviruses, thus making it an important target for drug development. We report here the first structure of full-length coronavirus helicase, MERS-CoV nsp13. MERS-CoV helicase has multiple domains, including an N-terminal Cys/His rich domain (CH) with three zinc atoms, a beta-barrel domain and a C-terminal SF1 helicase core with two RecA-like subdomains. Our structural analyses show that while the domain organization of nsp13 is conserved throughout nidoviruses, the individual domains of nsp13 are closely related to the equivalent eukaryotic domains of Upf1 helicases. The most distinctive feature differentiating CoV helicases from eukaryotic Upf1 helicases is the interaction between CH domain and helicase core.",2017 Jun 26,"['Hao, Wei', 'Wojdyla, Justyna Aleksandra', 'Zhao, Rong', 'Han, Ruiyun', 'Das, Rajat', 'Zlatev, Ivan', 'Manoharan, Muthiah', 'Wang, Meitian', 'Cui, Sheng']",PLoS Pathog,,,True
15d784a335abf0ea0266e9a2406b8d87f25c8f2f,PMC,T Cell–Derived IL-10 Impairs Host Resistance to Mycobacterium tuberculosis Infection,http://dx.doi.org/10.4049/jimmunol.1601340,PMC5502318,28584007,CC BY,"Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, is a leading cause of mortality and morbidity, causing ∼1.5 million deaths annually. CD4(+) T cells and several cytokines, such as the Th1 cytokine IFN-γ, are critical in the control of this infection. Conversely, the immunosuppressive cytokine IL-10 has been shown to dampen Th1 cell responses to M. tuberculosis infection impairing bacterial clearance. However, the critical cellular source of IL-10 during M. tuberculosis infection is still unknown. Using IL-10 reporter mice, we show in this article that during the first 14 d of M. tuberculosis infection, the predominant cells expressing IL-10 in the lung were Ly6C(+) monocytes. However, after day 21 postinfection, IL-10–expressing T cells were also highly represented. Notably, mice deficient in T cell–derived IL-10, but not mice deficient in monocyte-derived IL-10, showed a significant reduction in lung bacterial loads during chronic M. tuberculosis infection compared with fully IL-10–competent mice, indicating a major role for T cell–derived IL-10 in TB susceptibility. IL-10–expressing cells were detected among both CD4(+) and CD8(+) T cells, expressed high levels of CD44 and Tbet, and were able to coproduce IFN-γ and IL-10 upon ex vivo stimulation. Furthermore, during M. tuberculosis infection, Il10 expression in CD4(+) T cells was partially regulated by both IL-27 and type I IFN signaling. Together, our data reveal that, despite the multiple immune sources of IL-10 during M. tuberculosis infection, activated effector T cells are the major source accounting for IL-10–induced TB susceptibility.",2017 Jul 15,"['Moreira-Teixeira, Lúcia', 'Redford, Paul S.', 'Stavropoulos, Evangelos', 'Ghilardi, Nico', 'Maynard, Craig L.', 'Weaver, Casey T.', 'Freitas do Rosário, Ana Paula', 'Wu, Xuemei', 'Langhorne, Jean', 'O’Garra, Anne']",J Immunol,,,True
013ff749a58f92db7e227f7acbe47d050175851c,PMC,Full-Length Genome Sequence of Porcine Epidemic Diarrhea Virus Strain CH/GX/2015/750A,http://dx.doi.org/10.1128/genomeA.00361-17,PMC5502843,28684562,CC BY,"We report here the complete genome sequence of porcine epidemic diarrhea virus (PEDV) strain CH/GX/2015/750A (750A), which was isolated from a suckling piglet with watery diarrhea in Guangxi, China. The isolate is genetically close to other recent Chinese variant PEDVs and distinct from the classical PEDVs.",2017 Jul 6,"['Qin, Yibin', 'Lu, Bingxia', 'He, Ying', 'Li, Bin', 'Duan, Qunpeng', 'Liang, Jiaxing', 'Chen, Zhongwei', 'Su, Qianlian', 'Bi, Bingfen', 'Zhao, Wu']",Genome Announc,,,True
61810c29377a4573810dc313f4f5d526e7451c0d,PMC,Molecular features of influenza A (H1N1)pdm09 prevalent in Mexico during winter seasons 2012-2014,http://dx.doi.org/10.1371/journal.pone.0180419,PMC5503254,28692701,CC BY,"Since the emergence of the pandemic H1N1pdm09 virus in Mexico and California, biannual increases in the number of cases have been detected in Mexico. As observed in previous seasons, pandemic A/H1N1 09 virus was detected in severe cases during the 2011–2012 winter season and finally, during the 2013–2014 winter season it became the most prevalent influenza virus. Molecular and phylogenetic analyses of the whole viral genome are necessary to determine the antigenic and pathogenic characteristics of influenza viruses that cause severe outcomes of the disease. In this paper, we analyzed the evolution, antigenic and genetic drift of Mexican isolates from 2009, at the beginning of the pandemic, to 2014. We found a clear variation of the virus in Mexico from the 2011–2014 season due to different markers and in accordance with previous reports. In this study, we identified 13 novel substitutions with important biological effects, including virulence, T cell epitope presented by MHC and host specificity shift and some others substitutions might have more than one biological function. The systematic monitoring of mutations on whole genome of influenza A pH1N1 (2009) virus circulating at INER in Mexico City might provide valuable information to predict the emergence of new pathogenic influenza virus",2017 Jul 10,"['Arellano-Llamas, Rocío', 'Alfaro-Ruiz, Luis', 'Arriaga Canon, Cristian', 'Imaz Rosshandler, Ivan', 'Cruz-Lagunas, Alfredo', 'Zúñiga, Joaquín', 'Rebollar Vega, Rosa', 'Wong, Christopher W.', 'Maurer-Stroh, Sebastian', 'Romero Córdoba, Sandra', 'Liu, Edison T.', 'Hidalgo-Miranda, Alfredo', 'Vázquez-Pérez, Joel A.']",PLoS One,,,True
1dd28ef7fb600a0ca94980bcf6e5cbccf52a77fe,PMC,Solution conformations of Zika NS2B-NS3pro and its inhibition by natural products from edible plants,http://dx.doi.org/10.1371/journal.pone.0180632,PMC5503262,28700665,CC BY,"The recent Zika viral (ZIKV) epidemic has been associated with severe neurological pathologies such as neonatal microcephaly and Guillain-Barre syndrome but unfortunately no vaccine or medication is effectively available yet. Zika NS2B-NS3pro is essential for the proteolysis of the viral polyprotein and thereby viral replication. Thus NS2B-NS3pro represents an attractive target for anti-Zika drug discovery/design. Here, we have characterized the solution conformations and catalytic parameters of both linked and unlinked Zika NS2B-NS3pro complexes and found that the unlinked complex manifested well-dispersed NMR spectra. Subsequently with selective isotope-labeling using NMR spectroscopy, we demonstrated that C-terminal residues (R73-K100) of NS2B is highly disordered without any stable tertiary and secondary structures in the Zika NS2B-NS3pro complex in the free state. Upon binding to the well-characterized serine protease inhibitor, bovine pancreatic trypsin inhibitor (BPTI), only the extreme C-terminal residues (L86-K100) remain disordered. Additionally, we have identified five flavonoids and one natural phenol rich in edible plants including fruits and vegetables, which inhibit Zika NS2B-NS3pro in a non-competitive mode, with Ki ranging from 770 nM for Myricetin to 34.02 μM for Apigenin. Molecular docking showed that they all bind to a pocket on the back of the active site and their structure-activity relationship was elucidated. Our study provides valuable insights into the solution conformation of Zika NS2B-NS3pro and further deciphers its susceptibility towards allosteric inhibition by natural products. As these natural product inhibitors fundamentally differ from the currently-known active site inhibitors in terms of both inhibitory mode and chemical scaffold, our finding might open a new avenue for development of better allosteric inhibitors to fight ZIKV infection.",2017 Jul 10,"['Roy, Amrita', 'Lim, Liangzhong', 'Srivastava, Shagun', 'Lu, Yimei', 'Song, Jianxing']",PLoS One,,,True
d5d7c5ada2462aab2fa09789b1ef5ffe8e7f8d64,PMC,Diagnosis of cytomegalovirus pneumonia by quantitative polymerase chain reaction using bronchial washing fluid from patients with hematologic malignancies,http://dx.doi.org/10.18632/oncotarget.14504,PMC5503648,28061469,CC BY,"BACKGROUND: The incidence of cytomegalovirus (CMV) pneumonia is increasing in patients diagnosed with hematologic malignancies. The utility of CMV-DNA viral load measurement has not been standardized, and viral cut-off values have not been established. This study was designed to investigate the utility of CMV quantitative real-time PCR (qRT-PCR) using bronchial washing fluid. METHODS: We retrospectively reviewed the microbiologic and pathologic results of bronchial washing fluid and biopsy specimens in addition to the patients' clinical characteristics. RESULTS: A total of 565 CMV qRT-PCR assays were performed using bronchial washing fluid from patients with hematologic malignancies. Among them, 101 were positive for CMV by qRT-PCR; of these, 24 were diagnosed with CMV pneumonia and 70 with CMV infection, and 7 were excluded due to a diagnosis of invasive pulmonary aspergillosis rather than viral pneumonia. The median CMV load determined by qPCR was 1.8 × 10(5) copies/mL (3.6 10(3)-1.5 × 10(8)) in CMV pneumonia patients and 3.0 × 10(3) copies/mL (5.0 × 10(2)-1.1 × 10(5)) in those diagnosed with CMV infection (P < 0.01). Using the ROC curve, the optimal inflection points were 18,900 copies/mL (137,970 IU/mL) in post-bone marrow transplantation (BMT) patients, 316,415 copies/mL (2,309,825 IU/mL) in no-BMT patients and 28,774 copies/mL (210,054 IU/mL) in all patients. CONCLUSIONS: The CMV titers in bronchial washing fluid determined by qRT-PCR differed significantly between patients diagnosed with CMV pneumonia and those with CMV infection. The viral cut-off values in bronchial washing fluid were suggested for the diagnosis of CMV pneumonia, which were different depending on the BMT status.",2017 Jan 4,"['Lee, Hwa Young', 'Rhee, Chin Kook', 'Choi, Joon Young', 'Lee, Hea Yon', 'Lee, Jong Wook', 'Lee, Dong Gun']",Oncotarget,,,True
e383bf634defe24dbc8125cc85ddfb31ffffb7b6,PMC,Diagnosis of cytomegalovirus pneumonia by quantitative polymerase chain reaction using bronchial washing fluid from patients with hematologic malignancies,http://dx.doi.org/10.18632/oncotarget.14504,PMC5503648,28061469,CC BY,"BACKGROUND: The incidence of cytomegalovirus (CMV) pneumonia is increasing in patients diagnosed with hematologic malignancies. The utility of CMV-DNA viral load measurement has not been standardized, and viral cut-off values have not been established. This study was designed to investigate the utility of CMV quantitative real-time PCR (qRT-PCR) using bronchial washing fluid. METHODS: We retrospectively reviewed the microbiologic and pathologic results of bronchial washing fluid and biopsy specimens in addition to the patients' clinical characteristics. RESULTS: A total of 565 CMV qRT-PCR assays were performed using bronchial washing fluid from patients with hematologic malignancies. Among them, 101 were positive for CMV by qRT-PCR; of these, 24 were diagnosed with CMV pneumonia and 70 with CMV infection, and 7 were excluded due to a diagnosis of invasive pulmonary aspergillosis rather than viral pneumonia. The median CMV load determined by qPCR was 1.8 × 10(5) copies/mL (3.6 10(3)-1.5 × 10(8)) in CMV pneumonia patients and 3.0 × 10(3) copies/mL (5.0 × 10(2)-1.1 × 10(5)) in those diagnosed with CMV infection (P < 0.01). Using the ROC curve, the optimal inflection points were 18,900 copies/mL (137,970 IU/mL) in post-bone marrow transplantation (BMT) patients, 316,415 copies/mL (2,309,825 IU/mL) in no-BMT patients and 28,774 copies/mL (210,054 IU/mL) in all patients. CONCLUSIONS: The CMV titers in bronchial washing fluid determined by qRT-PCR differed significantly between patients diagnosed with CMV pneumonia and those with CMV infection. The viral cut-off values in bronchial washing fluid were suggested for the diagnosis of CMV pneumonia, which were different depending on the BMT status.",2017 Jan 4,"['Lee, Hwa Young', 'Rhee, Chin Kook', 'Choi, Joon Young', 'Lee, Hea Yon', 'Lee, Jong Wook', 'Lee, Dong Gun']",Oncotarget,,,False
72a39958a44d1a0664d01a1965b3afba46aea827,PMC,Cystatin D (CST5): An ultra-early inflammatory biomarker of traumatic brain injury,http://dx.doi.org/10.1038/s41598-017-04722-5,PMC5504020,28694499,CC BY,"Traumatic brain injury (TBI) is set to become the leading cause of neurological disability across all age groups. Currently, no reliable biomarkers exist to help diagnose the severity of TBI to identify patients who are at risk of developing secondary injuries. Thus, the discovery of reliable biomarkers for the management of TBI would improve clinical interventions. Inflammatory markers are particularly suited for biomarker discovery as TBI leads to very early alterations in inflammatory proteins. Using the Proseek Multiplex Inflammation assay, we measured in patients that had suffered mild TBI (n = 10) or severe TBI (n = 10) with extra-cranial injury or extracranial injury only (EC) (n = 10), 92 inflammation-associated proteins in serum obtained: <1 hr (within 1-hour), 4–12 hr and 48–72 hr post injury. Changes were compared to healthy volunteers (HV). Our results identified CST5, AXIN1 and TRAIL as novel early biomarkers of TBI. CST5 identified patients with severe TBI from all other cohorts and importantly was able to do so within the first hour of injury. AXIN1 and TRAIL were able to discriminate between TBI and HV at <1 hr. We conclude that CST5, AXIN1 and TRAIL are worthy of further study in the context of a pre-hospital or pitch-side test to detect brain injury.",2017 Jul 10,"['Hill, Lisa J.', 'Di Pietro, Valentina', 'Hazeldine, Jon', 'Davies, David', 'Toman, Emma', 'Logan, Ann', 'Belli, Antonio']",Sci Rep,,,True
ae423f7ae98fa3e8a1249bd193df1c09bdeedf7c,PMC,Two deletion variants of Middle East respiratory syndrome coronavirus found in a patient with characteristic symptoms,http://dx.doi.org/10.1007/s00705-017-3361-x,PMC5506503,28421366,CC BY,"Significant sequence variation of Middle East respiratory syndrome coronavirus (MERS CoV) has never been detected since it was first reported in 2012. A MERS patient came from Korea to China in late May 2015. The patient was 44 years old and had symptoms including high fever, dry cough with a little phlegm, and shortness of breath, which are roughly consistent with those associated with MERS, and had had close contact with individuals with confirmed cases of MERS.After one month of therapy with antiviral, anti-infection, and immune-enhancing agents, the patient recovered in the hospital and was discharged. A nasopharyngeal swab sample was collected for direct sequencing, which revealed two deletion variants of MERS CoV. Deletions of 414 and 419 nt occurred between ORF5 and the E protein, resulting in a partial protein fusion or truncation of ORF5 and the E protein. Functional analysis by bioinformatics and comparison to previous studies implied that the two variants might be defective in their ability to package MERS CoV. However, the mechanism of how these deletions occurred and what effects they have need to be further investigated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-017-3361-x) contains supplementary material, which is available to authorized users.",2017 Apr 18,"['Xie, Qian', 'Cao, Yujuan', 'Su, Juan', 'Wu, Jie', 'Wu, Xianbo', 'Wan, Chengsong', 'He, Mingliang', 'Ke, Changwen', 'Zhang, Bao', 'Zhao, Wei']",Arch Virol,,,True
fd6a5e41d7c2ffcd1079e540927707456897b6a8,PMC,Infants hospitalized for Bordetella pertussis infection commonly have respiratory viral coinfections,http://dx.doi.org/10.1186/s12879-017-2567-6,PMC5506634,28701160,CC BY,"BACKGROUND: Whether viral coinfections cause more severe disease than Bordetella pertussis (B. pertussis) alone remains unclear. We compared clinical disease severity and sought clinical and demographic differences between infants with B. pertussis infection alone and those with respiratory viral coinfections. We also analyzed how respiratory infections were distributed during the 2 years study. METHODS: We enrolled 53 infants with pertussis younger than 180 days (median age 58 days, range 17–109 days, 64.1% boys), hospitalized in the Pediatric Departments at “Sapienza” University Rome and Bambino Gesù Children’s Hospital from August 2012 to November 2014. We tested in naso-pharyngeal washings B. pertussis and 14 respiratory viruses with real-time reverse-transcriptase-polymerase chain reaction. Clinical data were obtained from hospital records and demographic characteristics collected using a structured questionnaire. RESULTS: 28/53 infants had B. pertussis alone and 25 viral coinfection: 10 human rhinovirus (9 alone and 1 in coinfection with parainfluenza virus), 3 human coronavirus, 2 respiratory syncytial virus. No differences were observed in clinical disease severity between infants with B. pertussis infection alone and those with coinfections. Infants with B. pertussis alone were younger than infants with coinfections, and less often breastfeed at admission. CONCLUSIONS: In this descriptive study, no associations between clinical severity and pertussis with or without co-infections were found. TRIAL REGISTRATION: Policlinico Umberto I: protocol 213/14, 3085/13.02.2014, retrospectively registered. Bambino Gesù Children’s Hospital: protocol n. RF-2010-2317709.",2017 Jul 12,"['Frassanito, A.', 'Nenna, R.', 'Nicolai, A.', 'Pierangeli, A.', 'Tozzi, A. E.', 'Stefanelli, P.', 'Carsetti, R.', 'Concato, C.', 'Schiavoni, I.', 'Midulla, F.', None]",BMC Infect Dis,,,True
c3411ca577f8a7a81a4bc8a3caff019243d75af9,PMC,Highly diverse and antimicrobial susceptible Escherichia coli display a naïve bacterial population in fruit bats from the Republic of Congo,http://dx.doi.org/10.1371/journal.pone.0178146,PMC5507484,28700648,CC BY,"Bats are suspected to be a reservoir of several bacterial and viral pathogens relevant to animal and human health, but studies on Escherichia coli in these animals are sparse. We investigated the presence of E. coli in tissue samples (liver, lung and intestines) collected from 50 fruit bats of five different species (Eidolon helvum, Epomops franqueti, Hypsignathus monstrosus, Myonycteris torquata, Rousettus aegyptiacus) of two different areas in the Republic of Congo between 2009 and 2010. To assess E. coli pathotypes and phylogenetic relationships, we determined the presence of 59 virulence associated genes and multilocus sequence types (STs). Isolates were further tested for their susceptibility to several antimicrobial substances by agar disk diffusion test and for the presence of an Extended-Spectrum Beta-Lactamase phenotype. E. coli was detected in 60% of the bats analysed. The diversity of E. coli strains was very high, with 37 different STs within 40 isolates. Occasionally, we detected sequence types (e.g. ST69, ST127, and ST131) and pathotypes (e.g. ExPEC, EPEC and atypical EPEC), which are known pathogens in human and/or animal infections. Although the majority of strains were assigned to phylogenetic group B2 (46.2%), which is linked with the ExPEC pathovar, occurrence of virulence-associated genes in these strains were unexpectedly low. Due to this, and as only few of the E. coli isolates showed intermediate resistance to certain antimicrobial substances, we assume a rather naïve E. coli population, lacking contact to humans or domestic animals. Future studies featuring in depth comparative whole genome sequence analyses will provide insights into the microevolution of this interesting strain collection.",2017 Jul 12,"['Nowak, Kathrin', 'Fahr, Jakob', 'Weber, Natalie', 'Lübke-Becker, Antina', 'Semmler, Torsten', 'Weiss, Sabrina', 'Mombouli, Jean-Vivien', 'Wieler, Lothar H.', 'Guenther, Sebastian', 'Leendertz, Fabian H.', 'Ewers, Christa']",PLoS One,,,True
a9bcb6e09eec3b0f6f6008e7d1c58b7923ed84c9,PMC,Highly diverse and antimicrobial susceptible Escherichia coli display a naïve bacterial population in fruit bats from the Republic of Congo,http://dx.doi.org/10.1371/journal.pone.0178146,PMC5507484,28700648,CC BY,"Bats are suspected to be a reservoir of several bacterial and viral pathogens relevant to animal and human health, but studies on Escherichia coli in these animals are sparse. We investigated the presence of E. coli in tissue samples (liver, lung and intestines) collected from 50 fruit bats of five different species (Eidolon helvum, Epomops franqueti, Hypsignathus monstrosus, Myonycteris torquata, Rousettus aegyptiacus) of two different areas in the Republic of Congo between 2009 and 2010. To assess E. coli pathotypes and phylogenetic relationships, we determined the presence of 59 virulence associated genes and multilocus sequence types (STs). Isolates were further tested for their susceptibility to several antimicrobial substances by agar disk diffusion test and for the presence of an Extended-Spectrum Beta-Lactamase phenotype. E. coli was detected in 60% of the bats analysed. The diversity of E. coli strains was very high, with 37 different STs within 40 isolates. Occasionally, we detected sequence types (e.g. ST69, ST127, and ST131) and pathotypes (e.g. ExPEC, EPEC and atypical EPEC), which are known pathogens in human and/or animal infections. Although the majority of strains were assigned to phylogenetic group B2 (46.2%), which is linked with the ExPEC pathovar, occurrence of virulence-associated genes in these strains were unexpectedly low. Due to this, and as only few of the E. coli isolates showed intermediate resistance to certain antimicrobial substances, we assume a rather naïve E. coli population, lacking contact to humans or domestic animals. Future studies featuring in depth comparative whole genome sequence analyses will provide insights into the microevolution of this interesting strain collection.",2017 Jul 12,"['Nowak, Kathrin', 'Fahr, Jakob', 'Weber, Natalie', 'Lübke-Becker, Antina', 'Semmler, Torsten', 'Weiss, Sabrina', 'Mombouli, Jean-Vivien', 'Wieler, Lothar H.', 'Guenther, Sebastian', 'Leendertz, Fabian H.', 'Ewers, Christa']",PLoS One,,,False
b3737686a53ecdaf9cd561fb7cea9b2af477a4e6,PMC,Highly diverse and antimicrobial susceptible Escherichia coli display a naïve bacterial population in fruit bats from the Republic of Congo,http://dx.doi.org/10.1371/journal.pone.0178146,PMC5507484,28700648,CC BY,"Bats are suspected to be a reservoir of several bacterial and viral pathogens relevant to animal and human health, but studies on Escherichia coli in these animals are sparse. We investigated the presence of E. coli in tissue samples (liver, lung and intestines) collected from 50 fruit bats of five different species (Eidolon helvum, Epomops franqueti, Hypsignathus monstrosus, Myonycteris torquata, Rousettus aegyptiacus) of two different areas in the Republic of Congo between 2009 and 2010. To assess E. coli pathotypes and phylogenetic relationships, we determined the presence of 59 virulence associated genes and multilocus sequence types (STs). Isolates were further tested for their susceptibility to several antimicrobial substances by agar disk diffusion test and for the presence of an Extended-Spectrum Beta-Lactamase phenotype. E. coli was detected in 60% of the bats analysed. The diversity of E. coli strains was very high, with 37 different STs within 40 isolates. Occasionally, we detected sequence types (e.g. ST69, ST127, and ST131) and pathotypes (e.g. ExPEC, EPEC and atypical EPEC), which are known pathogens in human and/or animal infections. Although the majority of strains were assigned to phylogenetic group B2 (46.2%), which is linked with the ExPEC pathovar, occurrence of virulence-associated genes in these strains were unexpectedly low. Due to this, and as only few of the E. coli isolates showed intermediate resistance to certain antimicrobial substances, we assume a rather naïve E. coli population, lacking contact to humans or domestic animals. Future studies featuring in depth comparative whole genome sequence analyses will provide insights into the microevolution of this interesting strain collection.",2017 Jul 12,"['Nowak, Kathrin', 'Fahr, Jakob', 'Weber, Natalie', 'Lübke-Becker, Antina', 'Semmler, Torsten', 'Weiss, Sabrina', 'Mombouli, Jean-Vivien', 'Wieler, Lothar H.', 'Guenther, Sebastian', 'Leendertz, Fabian H.', 'Ewers, Christa']",PLoS One,,,False
ca3c4ee5d633051312cd9853b0584fdd16937db8,PMC,Highly diverse and antimicrobial susceptible Escherichia coli display a naïve bacterial population in fruit bats from the Republic of Congo,http://dx.doi.org/10.1371/journal.pone.0178146,PMC5507484,28700648,CC BY,"Bats are suspected to be a reservoir of several bacterial and viral pathogens relevant to animal and human health, but studies on Escherichia coli in these animals are sparse. We investigated the presence of E. coli in tissue samples (liver, lung and intestines) collected from 50 fruit bats of five different species (Eidolon helvum, Epomops franqueti, Hypsignathus monstrosus, Myonycteris torquata, Rousettus aegyptiacus) of two different areas in the Republic of Congo between 2009 and 2010. To assess E. coli pathotypes and phylogenetic relationships, we determined the presence of 59 virulence associated genes and multilocus sequence types (STs). Isolates were further tested for their susceptibility to several antimicrobial substances by agar disk diffusion test and for the presence of an Extended-Spectrum Beta-Lactamase phenotype. E. coli was detected in 60% of the bats analysed. The diversity of E. coli strains was very high, with 37 different STs within 40 isolates. Occasionally, we detected sequence types (e.g. ST69, ST127, and ST131) and pathotypes (e.g. ExPEC, EPEC and atypical EPEC), which are known pathogens in human and/or animal infections. Although the majority of strains were assigned to phylogenetic group B2 (46.2%), which is linked with the ExPEC pathovar, occurrence of virulence-associated genes in these strains were unexpectedly low. Due to this, and as only few of the E. coli isolates showed intermediate resistance to certain antimicrobial substances, we assume a rather naïve E. coli population, lacking contact to humans or domestic animals. Future studies featuring in depth comparative whole genome sequence analyses will provide insights into the microevolution of this interesting strain collection.",2017 Jul 12,"['Nowak, Kathrin', 'Fahr, Jakob', 'Weber, Natalie', 'Lübke-Becker, Antina', 'Semmler, Torsten', 'Weiss, Sabrina', 'Mombouli, Jean-Vivien', 'Wieler, Lothar H.', 'Guenther, Sebastian', 'Leendertz, Fabian H.', 'Ewers, Christa']",PLoS One,,,False
01019f881b32e7484090bddb1f33148ab4bd883b,PMC,Highly diverse and antimicrobial susceptible Escherichia coli display a naïve bacterial population in fruit bats from the Republic of Congo,http://dx.doi.org/10.1371/journal.pone.0178146,PMC5507484,28700648,CC BY,"Bats are suspected to be a reservoir of several bacterial and viral pathogens relevant to animal and human health, but studies on Escherichia coli in these animals are sparse. We investigated the presence of E. coli in tissue samples (liver, lung and intestines) collected from 50 fruit bats of five different species (Eidolon helvum, Epomops franqueti, Hypsignathus monstrosus, Myonycteris torquata, Rousettus aegyptiacus) of two different areas in the Republic of Congo between 2009 and 2010. To assess E. coli pathotypes and phylogenetic relationships, we determined the presence of 59 virulence associated genes and multilocus sequence types (STs). Isolates were further tested for their susceptibility to several antimicrobial substances by agar disk diffusion test and for the presence of an Extended-Spectrum Beta-Lactamase phenotype. E. coli was detected in 60% of the bats analysed. The diversity of E. coli strains was very high, with 37 different STs within 40 isolates. Occasionally, we detected sequence types (e.g. ST69, ST127, and ST131) and pathotypes (e.g. ExPEC, EPEC and atypical EPEC), which are known pathogens in human and/or animal infections. Although the majority of strains were assigned to phylogenetic group B2 (46.2%), which is linked with the ExPEC pathovar, occurrence of virulence-associated genes in these strains were unexpectedly low. Due to this, and as only few of the E. coli isolates showed intermediate resistance to certain antimicrobial substances, we assume a rather naïve E. coli population, lacking contact to humans or domestic animals. Future studies featuring in depth comparative whole genome sequence analyses will provide insights into the microevolution of this interesting strain collection.",2017 Jul 12,"['Nowak, Kathrin', 'Fahr, Jakob', 'Weber, Natalie', 'Lübke-Becker, Antina', 'Semmler, Torsten', 'Weiss, Sabrina', 'Mombouli, Jean-Vivien', 'Wieler, Lothar H.', 'Guenther, Sebastian', 'Leendertz, Fabian H.', 'Ewers, Christa']",PLoS One,,,False
f3d3bfadf65b47af638cfe2bc0fab62aeca1bc90,PMC,Highly diverse and antimicrobial susceptible Escherichia coli display a naïve bacterial population in fruit bats from the Republic of Congo,http://dx.doi.org/10.1371/journal.pone.0178146,PMC5507484,28700648,CC BY,"Bats are suspected to be a reservoir of several bacterial and viral pathogens relevant to animal and human health, but studies on Escherichia coli in these animals are sparse. We investigated the presence of E. coli in tissue samples (liver, lung and intestines) collected from 50 fruit bats of five different species (Eidolon helvum, Epomops franqueti, Hypsignathus monstrosus, Myonycteris torquata, Rousettus aegyptiacus) of two different areas in the Republic of Congo between 2009 and 2010. To assess E. coli pathotypes and phylogenetic relationships, we determined the presence of 59 virulence associated genes and multilocus sequence types (STs). Isolates were further tested for their susceptibility to several antimicrobial substances by agar disk diffusion test and for the presence of an Extended-Spectrum Beta-Lactamase phenotype. E. coli was detected in 60% of the bats analysed. The diversity of E. coli strains was very high, with 37 different STs within 40 isolates. Occasionally, we detected sequence types (e.g. ST69, ST127, and ST131) and pathotypes (e.g. ExPEC, EPEC and atypical EPEC), which are known pathogens in human and/or animal infections. Although the majority of strains were assigned to phylogenetic group B2 (46.2%), which is linked with the ExPEC pathovar, occurrence of virulence-associated genes in these strains were unexpectedly low. Due to this, and as only few of the E. coli isolates showed intermediate resistance to certain antimicrobial substances, we assume a rather naïve E. coli population, lacking contact to humans or domestic animals. Future studies featuring in depth comparative whole genome sequence analyses will provide insights into the microevolution of this interesting strain collection.",2017 Jul 12,"['Nowak, Kathrin', 'Fahr, Jakob', 'Weber, Natalie', 'Lübke-Becker, Antina', 'Semmler, Torsten', 'Weiss, Sabrina', 'Mombouli, Jean-Vivien', 'Wieler, Lothar H.', 'Guenther, Sebastian', 'Leendertz, Fabian H.', 'Ewers, Christa']",PLoS One,,,False
8be33a516142d0fa91dd2355a5d41a5357895188,PMC,Identification of Interactions between Sindbis Virus Capsid Protein and Cytoplasmic vRNA as Novel Virulence Determinants,http://dx.doi.org/10.1371/journal.ppat.1006473,PMC5507600,28662211,CC BY,"Alphaviruses are arthropod-borne viruses that represent a significant threat to public health at a global level. While the formation of alphaviral nucleocapsid cores, consisting of cargo nucleic acid and the viral capsid protein, is an essential molecular process of infection, the precise interactions between the two partners are ill-defined. A CLIP-seq approach was used to screen for candidate sites of interaction between the viral Capsid protein and genomic RNA of Sindbis virus (SINV), a model alphavirus. The data presented in this report indicates that the SINV capsid protein binds to specific viral RNA sequences in the cytoplasm of infected cells, but its interaction with genomic RNA in mature extracellular viral particles is largely non-specific in terms of nucleotide sequence. Mutational analyses of the cytoplasmic viral RNA-capsid interaction sites revealed a functional role for capsid binding early in infection. Interaction site mutants exhibited decreased viral growth kinetics; however, this defect was not a function of decreased particle production. Rather mutation of the cytoplasmic capsid-RNA interaction sites negatively affected the functional capacity of the incoming viral genomic RNAs leading to decreased infectivity. Furthermore, cytoplasmic capsid interaction site mutants are attenuated in a murine model of neurotropic alphavirus infection. Collectively, the findings of this study indicate that the identified cytoplasmic interactions of the viral capsid protein and genomic RNA, while not essential for particle formation, are necessary for genomic RNA function early during infection. This previously unappreciated role of capsid protein during the alphaviral replication cycle also constitutes a novel virulence determinant.",2017 Jun 29,"['Sokoloski, Kevin J.', 'Nease, Lauren M.', 'May, Nicholas A.', 'Gebhart, Natasha N.', 'Jones, Claire E.', 'Morrison, Thomas E.', 'Hardy, Richard W.']",PLoS Pathog,,,True
7211a81083ed907afe1ecbda662b31fae9838f0e,PMC,Identification of Interactions between Sindbis Virus Capsid Protein and Cytoplasmic vRNA as Novel Virulence Determinants,http://dx.doi.org/10.1371/journal.ppat.1006473,PMC5507600,28662211,CC BY,"Alphaviruses are arthropod-borne viruses that represent a significant threat to public health at a global level. While the formation of alphaviral nucleocapsid cores, consisting of cargo nucleic acid and the viral capsid protein, is an essential molecular process of infection, the precise interactions between the two partners are ill-defined. A CLIP-seq approach was used to screen for candidate sites of interaction between the viral Capsid protein and genomic RNA of Sindbis virus (SINV), a model alphavirus. The data presented in this report indicates that the SINV capsid protein binds to specific viral RNA sequences in the cytoplasm of infected cells, but its interaction with genomic RNA in mature extracellular viral particles is largely non-specific in terms of nucleotide sequence. Mutational analyses of the cytoplasmic viral RNA-capsid interaction sites revealed a functional role for capsid binding early in infection. Interaction site mutants exhibited decreased viral growth kinetics; however, this defect was not a function of decreased particle production. Rather mutation of the cytoplasmic capsid-RNA interaction sites negatively affected the functional capacity of the incoming viral genomic RNAs leading to decreased infectivity. Furthermore, cytoplasmic capsid interaction site mutants are attenuated in a murine model of neurotropic alphavirus infection. Collectively, the findings of this study indicate that the identified cytoplasmic interactions of the viral capsid protein and genomic RNA, while not essential for particle formation, are necessary for genomic RNA function early during infection. This previously unappreciated role of capsid protein during the alphaviral replication cycle also constitutes a novel virulence determinant.",2017 Jun 29,"['Sokoloski, Kevin J.', 'Nease, Lauren M.', 'May, Nicholas A.', 'Gebhart, Natasha N.', 'Jones, Claire E.', 'Morrison, Thomas E.', 'Hardy, Richard W.']",PLoS Pathog,,,False
ccd537b92136e3c66ddb7b0abac70c4f7765fb8b,PMC,Editorial: Biological Engagement Programs: Reducing Threats and Strengthening Global Health Security Through Scientific Collaboration,http://dx.doi.org/10.3389/fpubh.2017.00148,PMC5508190,28752086,CC BY,,2017 Jul 12,"Fair, Jeanne M.",Front Public Health,,,True
f456aeb3d2dd8f321a23068ec9ed25c611b819e7,PMC,"Experience with a Multinational, Secondary School Education Module with a Focus on Prevention of Virus Infections",http://dx.doi.org/10.4269/ajtmh.16-0661,PMC5508890,28719318,CC BY,"Worldwide, virus infections are responsible for many diseases in terms of morbidity and mortality. Vaccinations and therapies are only available for relatively few virus infections and not always where they are needed. However, knowledge of transmission routes can prevent virus infection. In the context of this study, we measured the effects of a secondary school education module, named Viruskenner, on knowledge, attitude, and risk behavior as these relate to virus infections. A nonrandomized intervention study was conducted between April and August 2015 to assess the effect of this 2-month education module on knowledge, attitude, and behavior of 684 secondary school students in the Netherlands, Suriname, and Indonesia. For the Netherlands, a control group of a further 184 students was added. Factor analysis was performed on questions pertaining to attitude and behavior. Comparative analyses between pre- and posttest per country were done using multiple linear regression, independent sample T-tests, and one-way analysis of variance. These showed a significant increase in knowledge about virus infections and the prevention of infectious diseases among the Dutch and Surinamese groups, whereas a trend of increased knowledge was evident among the Indonesian participants. The Dutch control group showed an overall decrease in knowledge. Regression analyses showed that there was a significant interaction effect between participation and time on knowledge, attitude, and awareness and behavior and risk infection. Attitudes improved significantly in the intervention group. Pearson correlation coefficients between knowledge, attitude, and behavior were found to be positive.",2017 Jul 12,"['Doornekamp, Laura', 'Stegers-Jager, Karen M.', 'Vlek, Odette M.', 'Klop, Tanja', 'Goeijenbier, Marco', 'van Gorp, Eric C. M.']",Am J Trop Med Hyg,,,True
8646d9e78f266ac92f1357bd161bf14a9bd3d2c2,PMC,"Experience with a Multinational, Secondary School Education Module with a Focus on Prevention of Virus Infections",http://dx.doi.org/10.4269/ajtmh.16-0661,PMC5508890,28719318,CC BY,"Worldwide, virus infections are responsible for many diseases in terms of morbidity and mortality. Vaccinations and therapies are only available for relatively few virus infections and not always where they are needed. However, knowledge of transmission routes can prevent virus infection. In the context of this study, we measured the effects of a secondary school education module, named Viruskenner, on knowledge, attitude, and risk behavior as these relate to virus infections. A nonrandomized intervention study was conducted between April and August 2015 to assess the effect of this 2-month education module on knowledge, attitude, and behavior of 684 secondary school students in the Netherlands, Suriname, and Indonesia. For the Netherlands, a control group of a further 184 students was added. Factor analysis was performed on questions pertaining to attitude and behavior. Comparative analyses between pre- and posttest per country were done using multiple linear regression, independent sample T-tests, and one-way analysis of variance. These showed a significant increase in knowledge about virus infections and the prevention of infectious diseases among the Dutch and Surinamese groups, whereas a trend of increased knowledge was evident among the Indonesian participants. The Dutch control group showed an overall decrease in knowledge. Regression analyses showed that there was a significant interaction effect between participation and time on knowledge, attitude, and awareness and behavior and risk infection. Attitudes improved significantly in the intervention group. Pearson correlation coefficients between knowledge, attitude, and behavior were found to be positive.",2017 Jul 12,"['Doornekamp, Laura', 'Stegers-Jager, Karen M.', 'Vlek, Odette M.', 'Klop, Tanja', 'Goeijenbier, Marco', 'van Gorp, Eric C. M.']",Am J Trop Med Hyg,,,False
286bea94529dca847214023bb3eabc8b2bc59760,PMC,"Severity of Pneumonia in Under 5-Year-Old Children from Developing Countries: A Multicenter, Prospective, Observational Study",http://dx.doi.org/10.4269/ajtmh.16-0733,PMC5508893,28719310,CC BY,"Pneumonia is the leading cause of death in children. The objectives were to evaluate the microbiological agents linked with hypoxemia in hospitalized children with pneumonia from developing countries, to identify predictors of hypoxemia, and to characterize factors associated with in-hospital mortality. A multicenter, observational study was conducted in five hospitals, from India (Lucknow, Vadu), Madagascar (Antananarivo), Mali (Bamako), and Paraguay (San Lorenzo). Children aged 2–60 months with radiologically confirmed pneumonia were enrolled prospectively. Respiratory and whole blood specimens were collected, identifying viruses and bacteria by real-time multiplex polymerase chain reaction (PCR). Microbiological agents linked with hypoxemia at admission (oxygen saturation < 90%) were analyzed by multivariate logistic regression, and factors associated with 14-day in-hospital mortality were assessed by bivariate Cox regression. Overall, 405 pneumonia cases (3,338 hospitalization days) were analyzed; 13 patients died within 14 days of hospitalization. Hypoxemia prevalence was 17.3%. Detection of human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) in respiratory samples was independently associated with increased risk of hypoxemia (adjusted odds ratio [aOR] = 2.4, 95% confidence interval [95% CI] = 1.0–5.8 and aOR = 2.5, 95% CI = 1.1–5.3, respectively). Lower chest indrawing and cyanosis were predictive of hypoxemia (positive likelihood ratios = 2.3 and 2.4, respectively). Predictors of death were Streptococcus pneumoniae detection by blood PCR (crude hazard ratio [cHR] = 4.6, 95% CI = 1.5–14.0), procalcitonin ≥ 50 ng/mL (cHR = 22.4, 95% CI = 7.3–68.5) and hypoxemia (cHR = 4.8, 95% CI = 1.6–14.4). These findings were consistent on bivariate analysis. hMPV and RSV in respiratory samples were linked with hypoxemia, and S. pneumoniae in blood was associated with increased risk of death among hospitalized children with pneumonia in developing countries.",2017 Jul 12,"['Bénet, Thomas', 'Picot, Valentina Sanchez', 'Awasthi, Shally', 'Pandey, Nitin', 'Bavdekar, Ashish', 'Kawade, Anand', 'Robinson, Annick', 'Rakoto-Andrianarivelo, Mala', 'Sylla, Maryam', 'Diallo, Souleymane', 'Russomando, Graciela', 'Basualdo, Wilma', 'Komurian-Pradel, Florence', 'Endtz, Hubert', 'Vanhems, Philippe', 'Paranhos-Baccalà, Gláucia', None]",Am J Trop Med Hyg,,,True
e754b5f82225ca4d132cc3fce0d3773e2f563f2f,PMC,"Severity of Pneumonia in Under 5-Year-Old Children from Developing Countries: A Multicenter, Prospective, Observational Study",http://dx.doi.org/10.4269/ajtmh.16-0733,PMC5508893,28719310,CC BY,"Pneumonia is the leading cause of death in children. The objectives were to evaluate the microbiological agents linked with hypoxemia in hospitalized children with pneumonia from developing countries, to identify predictors of hypoxemia, and to characterize factors associated with in-hospital mortality. A multicenter, observational study was conducted in five hospitals, from India (Lucknow, Vadu), Madagascar (Antananarivo), Mali (Bamako), and Paraguay (San Lorenzo). Children aged 2–60 months with radiologically confirmed pneumonia were enrolled prospectively. Respiratory and whole blood specimens were collected, identifying viruses and bacteria by real-time multiplex polymerase chain reaction (PCR). Microbiological agents linked with hypoxemia at admission (oxygen saturation < 90%) were analyzed by multivariate logistic regression, and factors associated with 14-day in-hospital mortality were assessed by bivariate Cox regression. Overall, 405 pneumonia cases (3,338 hospitalization days) were analyzed; 13 patients died within 14 days of hospitalization. Hypoxemia prevalence was 17.3%. Detection of human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) in respiratory samples was independently associated with increased risk of hypoxemia (adjusted odds ratio [aOR] = 2.4, 95% confidence interval [95% CI] = 1.0–5.8 and aOR = 2.5, 95% CI = 1.1–5.3, respectively). Lower chest indrawing and cyanosis were predictive of hypoxemia (positive likelihood ratios = 2.3 and 2.4, respectively). Predictors of death were Streptococcus pneumoniae detection by blood PCR (crude hazard ratio [cHR] = 4.6, 95% CI = 1.5–14.0), procalcitonin ≥ 50 ng/mL (cHR = 22.4, 95% CI = 7.3–68.5) and hypoxemia (cHR = 4.8, 95% CI = 1.6–14.4). These findings were consistent on bivariate analysis. hMPV and RSV in respiratory samples were linked with hypoxemia, and S. pneumoniae in blood was associated with increased risk of death among hospitalized children with pneumonia in developing countries.",2017 Jul 12,"['Bénet, Thomas', 'Picot, Valentina Sanchez', 'Awasthi, Shally', 'Pandey, Nitin', 'Bavdekar, Ashish', 'Kawade, Anand', 'Robinson, Annick', 'Rakoto-Andrianarivelo, Mala', 'Sylla, Maryam', 'Diallo, Souleymane', 'Russomando, Graciela', 'Basualdo, Wilma', 'Komurian-Pradel, Florence', 'Endtz, Hubert', 'Vanhems, Philippe', 'Paranhos-Baccalà, Gláucia', None]",Am J Trop Med Hyg,,,False
40cdf2909c24827365de82a6a5d84a7c3aec0290,PMC,Are disease reservoirs special? Taxonomic and life history characteristics,http://dx.doi.org/10.1371/journal.pone.0180716,PMC5509157,28704402,CC BY,"Pathogens that spill over between species cause a significant human and animal health burden. Here, we describe characteristics of animal reservoirs that are required for pathogen spillover. We assembled and analyzed a database of 330 disease systems in which a pathogen spills over from a reservoir of one or more species. Three-quarters of reservoirs included wildlife, and 84% included mammals. Further, 65% of pathogens depended on a community of reservoir hosts, rather than a single species, for persistence. Among mammals, the most frequently identified reservoir hosts were rodents, artiodactyls, and carnivores. The distribution among orders of mammalian species identified as reservoirs did not differ from that expected by chance. Among disease systems with high priority pathogens and epidemic potential, we found birds, primates, and bats to be overrepresented. We also analyzed the life history traits of mammalian reservoir hosts and compared them to mammals as a whole. Reservoir species had faster life history characteristics than mammals overall, exhibiting traits associated with greater reproductive output rather than long-term survival. Thus, we find that in many respects, reservoirs of spillover pathogens are indeed special. The described patterns provide a useful resource for studying and managing emerging infectious diseases.",2017 Jul 13,"['Plourde, Benjamin T.', 'Burgess, Tristan L.', 'Eskew, Evan A.', 'Roth, Tara M.', 'Stephenson, Nicole', 'Foley, Janet E.']",PLoS One,,,True
62067c9aa24d6b8cbd2a02101c4d4e34681fab97,PMC,Are disease reservoirs special? Taxonomic and life history characteristics,http://dx.doi.org/10.1371/journal.pone.0180716,PMC5509157,28704402,CC BY,"Pathogens that spill over between species cause a significant human and animal health burden. Here, we describe characteristics of animal reservoirs that are required for pathogen spillover. We assembled and analyzed a database of 330 disease systems in which a pathogen spills over from a reservoir of one or more species. Three-quarters of reservoirs included wildlife, and 84% included mammals. Further, 65% of pathogens depended on a community of reservoir hosts, rather than a single species, for persistence. Among mammals, the most frequently identified reservoir hosts were rodents, artiodactyls, and carnivores. The distribution among orders of mammalian species identified as reservoirs did not differ from that expected by chance. Among disease systems with high priority pathogens and epidemic potential, we found birds, primates, and bats to be overrepresented. We also analyzed the life history traits of mammalian reservoir hosts and compared them to mammals as a whole. Reservoir species had faster life history characteristics than mammals overall, exhibiting traits associated with greater reproductive output rather than long-term survival. Thus, we find that in many respects, reservoirs of spillover pathogens are indeed special. The described patterns provide a useful resource for studying and managing emerging infectious diseases.",2017 Jul 13,"['Plourde, Benjamin T.', 'Burgess, Tristan L.', 'Eskew, Evan A.', 'Roth, Tara M.', 'Stephenson, Nicole', 'Foley, Janet E.']",PLoS One,,,True
2bad606f9756b0035be211494df2dc4677b90425,PMC,Are disease reservoirs special? Taxonomic and life history characteristics,http://dx.doi.org/10.1371/journal.pone.0180716,PMC5509157,28704402,CC BY,"Pathogens that spill over between species cause a significant human and animal health burden. Here, we describe characteristics of animal reservoirs that are required for pathogen spillover. We assembled and analyzed a database of 330 disease systems in which a pathogen spills over from a reservoir of one or more species. Three-quarters of reservoirs included wildlife, and 84% included mammals. Further, 65% of pathogens depended on a community of reservoir hosts, rather than a single species, for persistence. Among mammals, the most frequently identified reservoir hosts were rodents, artiodactyls, and carnivores. The distribution among orders of mammalian species identified as reservoirs did not differ from that expected by chance. Among disease systems with high priority pathogens and epidemic potential, we found birds, primates, and bats to be overrepresented. We also analyzed the life history traits of mammalian reservoir hosts and compared them to mammals as a whole. Reservoir species had faster life history characteristics than mammals overall, exhibiting traits associated with greater reproductive output rather than long-term survival. Thus, we find that in many respects, reservoirs of spillover pathogens are indeed special. The described patterns provide a useful resource for studying and managing emerging infectious diseases.",2017 Jul 13,"['Plourde, Benjamin T.', 'Burgess, Tristan L.', 'Eskew, Evan A.', 'Roth, Tara M.', 'Stephenson, Nicole', 'Foley, Janet E.']",PLoS One,,,False
1f6c99532bdd272b5c59dc16ed9e9510d6523dd9,PMC,Are disease reservoirs special? Taxonomic and life history characteristics,http://dx.doi.org/10.1371/journal.pone.0180716,PMC5509157,28704402,CC BY,"Pathogens that spill over between species cause a significant human and animal health burden. Here, we describe characteristics of animal reservoirs that are required for pathogen spillover. We assembled and analyzed a database of 330 disease systems in which a pathogen spills over from a reservoir of one or more species. Three-quarters of reservoirs included wildlife, and 84% included mammals. Further, 65% of pathogens depended on a community of reservoir hosts, rather than a single species, for persistence. Among mammals, the most frequently identified reservoir hosts were rodents, artiodactyls, and carnivores. The distribution among orders of mammalian species identified as reservoirs did not differ from that expected by chance. Among disease systems with high priority pathogens and epidemic potential, we found birds, primates, and bats to be overrepresented. We also analyzed the life history traits of mammalian reservoir hosts and compared them to mammals as a whole. Reservoir species had faster life history characteristics than mammals overall, exhibiting traits associated with greater reproductive output rather than long-term survival. Thus, we find that in many respects, reservoirs of spillover pathogens are indeed special. The described patterns provide a useful resource for studying and managing emerging infectious diseases.",2017 Jul 13,"['Plourde, Benjamin T.', 'Burgess, Tristan L.', 'Eskew, Evan A.', 'Roth, Tara M.', 'Stephenson, Nicole', 'Foley, Janet E.']",PLoS One,,,False
e35b917afa97ab15c4f02e50a563bd5edb7ce963,PMC,Are disease reservoirs special? Taxonomic and life history characteristics,http://dx.doi.org/10.1371/journal.pone.0180716,PMC5509157,28704402,CC BY,"Pathogens that spill over between species cause a significant human and animal health burden. Here, we describe characteristics of animal reservoirs that are required for pathogen spillover. We assembled and analyzed a database of 330 disease systems in which a pathogen spills over from a reservoir of one or more species. Three-quarters of reservoirs included wildlife, and 84% included mammals. Further, 65% of pathogens depended on a community of reservoir hosts, rather than a single species, for persistence. Among mammals, the most frequently identified reservoir hosts were rodents, artiodactyls, and carnivores. The distribution among orders of mammalian species identified as reservoirs did not differ from that expected by chance. Among disease systems with high priority pathogens and epidemic potential, we found birds, primates, and bats to be overrepresented. We also analyzed the life history traits of mammalian reservoir hosts and compared them to mammals as a whole. Reservoir species had faster life history characteristics than mammals overall, exhibiting traits associated with greater reproductive output rather than long-term survival. Thus, we find that in many respects, reservoirs of spillover pathogens are indeed special. The described patterns provide a useful resource for studying and managing emerging infectious diseases.",2017 Jul 13,"['Plourde, Benjamin T.', 'Burgess, Tristan L.', 'Eskew, Evan A.', 'Roth, Tara M.', 'Stephenson, Nicole', 'Foley, Janet E.']",PLoS One,,,False
c96924f598532161e902de5908a51d06ff0f66b1,PMC,Are disease reservoirs special? Taxonomic and life history characteristics,http://dx.doi.org/10.1371/journal.pone.0180716,PMC5509157,28704402,CC BY,"Pathogens that spill over between species cause a significant human and animal health burden. Here, we describe characteristics of animal reservoirs that are required for pathogen spillover. We assembled and analyzed a database of 330 disease systems in which a pathogen spills over from a reservoir of one or more species. Three-quarters of reservoirs included wildlife, and 84% included mammals. Further, 65% of pathogens depended on a community of reservoir hosts, rather than a single species, for persistence. Among mammals, the most frequently identified reservoir hosts were rodents, artiodactyls, and carnivores. The distribution among orders of mammalian species identified as reservoirs did not differ from that expected by chance. Among disease systems with high priority pathogens and epidemic potential, we found birds, primates, and bats to be overrepresented. We also analyzed the life history traits of mammalian reservoir hosts and compared them to mammals as a whole. Reservoir species had faster life history characteristics than mammals overall, exhibiting traits associated with greater reproductive output rather than long-term survival. Thus, we find that in many respects, reservoirs of spillover pathogens are indeed special. The described patterns provide a useful resource for studying and managing emerging infectious diseases.",2017 Jul 13,"['Plourde, Benjamin T.', 'Burgess, Tristan L.', 'Eskew, Evan A.', 'Roth, Tara M.', 'Stephenson, Nicole', 'Foley, Janet E.']",PLoS One,,,False
91f881edacdef087138521e2a8b983f464288462,PMC,Are disease reservoirs special? Taxonomic and life history characteristics,http://dx.doi.org/10.1371/journal.pone.0180716,PMC5509157,28704402,CC BY,"Pathogens that spill over between species cause a significant human and animal health burden. Here, we describe characteristics of animal reservoirs that are required for pathogen spillover. We assembled and analyzed a database of 330 disease systems in which a pathogen spills over from a reservoir of one or more species. Three-quarters of reservoirs included wildlife, and 84% included mammals. Further, 65% of pathogens depended on a community of reservoir hosts, rather than a single species, for persistence. Among mammals, the most frequently identified reservoir hosts were rodents, artiodactyls, and carnivores. The distribution among orders of mammalian species identified as reservoirs did not differ from that expected by chance. Among disease systems with high priority pathogens and epidemic potential, we found birds, primates, and bats to be overrepresented. We also analyzed the life history traits of mammalian reservoir hosts and compared them to mammals as a whole. Reservoir species had faster life history characteristics than mammals overall, exhibiting traits associated with greater reproductive output rather than long-term survival. Thus, we find that in many respects, reservoirs of spillover pathogens are indeed special. The described patterns provide a useful resource for studying and managing emerging infectious diseases.",2017 Jul 13,"['Plourde, Benjamin T.', 'Burgess, Tristan L.', 'Eskew, Evan A.', 'Roth, Tara M.', 'Stephenson, Nicole', 'Foley, Janet E.']",PLoS One,,,False
bb4f42ef4c3f6f79f00cefa411b9f28aeca5772c,PMC,Are disease reservoirs special? Taxonomic and life history characteristics,http://dx.doi.org/10.1371/journal.pone.0180716,PMC5509157,28704402,CC BY,"Pathogens that spill over between species cause a significant human and animal health burden. Here, we describe characteristics of animal reservoirs that are required for pathogen spillover. We assembled and analyzed a database of 330 disease systems in which a pathogen spills over from a reservoir of one or more species. Three-quarters of reservoirs included wildlife, and 84% included mammals. Further, 65% of pathogens depended on a community of reservoir hosts, rather than a single species, for persistence. Among mammals, the most frequently identified reservoir hosts were rodents, artiodactyls, and carnivores. The distribution among orders of mammalian species identified as reservoirs did not differ from that expected by chance. Among disease systems with high priority pathogens and epidemic potential, we found birds, primates, and bats to be overrepresented. We also analyzed the life history traits of mammalian reservoir hosts and compared them to mammals as a whole. Reservoir species had faster life history characteristics than mammals overall, exhibiting traits associated with greater reproductive output rather than long-term survival. Thus, we find that in many respects, reservoirs of spillover pathogens are indeed special. The described patterns provide a useful resource for studying and managing emerging infectious diseases.",2017 Jul 13,"['Plourde, Benjamin T.', 'Burgess, Tristan L.', 'Eskew, Evan A.', 'Roth, Tara M.', 'Stephenson, Nicole', 'Foley, Janet E.']",PLoS One,,,False
096c6b096573feae648f18bee7d6f295f64b056c,PMC,Are disease reservoirs special? Taxonomic and life history characteristics,http://dx.doi.org/10.1371/journal.pone.0180716,PMC5509157,28704402,CC BY,"Pathogens that spill over between species cause a significant human and animal health burden. Here, we describe characteristics of animal reservoirs that are required for pathogen spillover. We assembled and analyzed a database of 330 disease systems in which a pathogen spills over from a reservoir of one or more species. Three-quarters of reservoirs included wildlife, and 84% included mammals. Further, 65% of pathogens depended on a community of reservoir hosts, rather than a single species, for persistence. Among mammals, the most frequently identified reservoir hosts were rodents, artiodactyls, and carnivores. The distribution among orders of mammalian species identified as reservoirs did not differ from that expected by chance. Among disease systems with high priority pathogens and epidemic potential, we found birds, primates, and bats to be overrepresented. We also analyzed the life history traits of mammalian reservoir hosts and compared them to mammals as a whole. Reservoir species had faster life history characteristics than mammals overall, exhibiting traits associated with greater reproductive output rather than long-term survival. Thus, we find that in many respects, reservoirs of spillover pathogens are indeed special. The described patterns provide a useful resource for studying and managing emerging infectious diseases.",2017 Jul 13,"['Plourde, Benjamin T.', 'Burgess, Tristan L.', 'Eskew, Evan A.', 'Roth, Tara M.', 'Stephenson, Nicole', 'Foley, Janet E.']",PLoS One,,,False
97b92a48baff3f1f723d25d0690ce9d3b733673d,PMC,Are disease reservoirs special? Taxonomic and life history characteristics,http://dx.doi.org/10.1371/journal.pone.0180716,PMC5509157,28704402,CC BY,"Pathogens that spill over between species cause a significant human and animal health burden. Here, we describe characteristics of animal reservoirs that are required for pathogen spillover. We assembled and analyzed a database of 330 disease systems in which a pathogen spills over from a reservoir of one or more species. Three-quarters of reservoirs included wildlife, and 84% included mammals. Further, 65% of pathogens depended on a community of reservoir hosts, rather than a single species, for persistence. Among mammals, the most frequently identified reservoir hosts were rodents, artiodactyls, and carnivores. The distribution among orders of mammalian species identified as reservoirs did not differ from that expected by chance. Among disease systems with high priority pathogens and epidemic potential, we found birds, primates, and bats to be overrepresented. We also analyzed the life history traits of mammalian reservoir hosts and compared them to mammals as a whole. Reservoir species had faster life history characteristics than mammals overall, exhibiting traits associated with greater reproductive output rather than long-term survival. Thus, we find that in many respects, reservoirs of spillover pathogens are indeed special. The described patterns provide a useful resource for studying and managing emerging infectious diseases.",2017 Jul 13,"['Plourde, Benjamin T.', 'Burgess, Tristan L.', 'Eskew, Evan A.', 'Roth, Tara M.', 'Stephenson, Nicole', 'Foley, Janet E.']",PLoS One,,,False
9bd1da1bb4018280eb010f0299b44046c9de9889,PMC,Kanyawara Virus: A Novel Rhabdovirus Infecting Newly Discovered Nycteribiid Bat Flies Infesting Previously Unknown Pteropodid Bats in Uganda,http://dx.doi.org/10.1038/s41598-017-05236-w,PMC5509700,28706276,CC BY,"Bats are natural reservoir hosts of highly virulent pathogens such as Marburg virus, Nipah virus, and SARS coronavirus. However, little is known about the role of bat ectoparasites in transmitting and maintaining such viruses. The intricate relationship between bats and their ectoparasites suggests that ectoparasites might serve as viral vectors, but evidence to date is scant. Bat flies, in particular, are highly specialized obligate hematophagous ectoparasites that incidentally bite humans. Using next-generation sequencing, we discovered a novel ledantevirus (mononegaviral family Rhabdoviridae, genus Ledantevirus) in nycteribiid bat flies infesting pteropodid bats in western Uganda. Mitochondrial DNA analyses revealed that both the bat flies and their bat hosts belong to putative new species. The coding-complete genome of the new virus, named Kanyawara virus (KYAV), is only distantly related to that of its closest known relative, Mount Elgon bat virus, and was found at high titers in bat flies but not in blood or on mucosal surfaces of host bats. Viral genome analysis indicates unusually low CpG dinucleotide depletion in KYAV compared to other ledanteviruses and rhabdovirus groups, with KYAV displaying values similar to rhabdoviruses of arthropods. Our findings highlight the possibility of a yet-to-be-discovered diversity of potentially pathogenic viruses in bat ectoparasites.",2017 Jul 13,"['Goldberg, Tony L.', 'Bennett, Andrew J.', 'Kityo, Robert', 'Kuhn, Jens H.', 'Chapman, Colin A.']",Sci Rep,,,False
699ffcdbc72afc6d6243a7d0dbd50cc055d03aeb,PMC,Kanyawara Virus: A Novel Rhabdovirus Infecting Newly Discovered Nycteribiid Bat Flies Infesting Previously Unknown Pteropodid Bats in Uganda,http://dx.doi.org/10.1038/s41598-017-05236-w,PMC5509700,28706276,CC BY,"Bats are natural reservoir hosts of highly virulent pathogens such as Marburg virus, Nipah virus, and SARS coronavirus. However, little is known about the role of bat ectoparasites in transmitting and maintaining such viruses. The intricate relationship between bats and their ectoparasites suggests that ectoparasites might serve as viral vectors, but evidence to date is scant. Bat flies, in particular, are highly specialized obligate hematophagous ectoparasites that incidentally bite humans. Using next-generation sequencing, we discovered a novel ledantevirus (mononegaviral family Rhabdoviridae, genus Ledantevirus) in nycteribiid bat flies infesting pteropodid bats in western Uganda. Mitochondrial DNA analyses revealed that both the bat flies and their bat hosts belong to putative new species. The coding-complete genome of the new virus, named Kanyawara virus (KYAV), is only distantly related to that of its closest known relative, Mount Elgon bat virus, and was found at high titers in bat flies but not in blood or on mucosal surfaces of host bats. Viral genome analysis indicates unusually low CpG dinucleotide depletion in KYAV compared to other ledanteviruses and rhabdovirus groups, with KYAV displaying values similar to rhabdoviruses of arthropods. Our findings highlight the possibility of a yet-to-be-discovered diversity of potentially pathogenic viruses in bat ectoparasites.",2017 Jul 13,"['Goldberg, Tony L.', 'Bennett, Andrew J.', 'Kityo, Robert', 'Kuhn, Jens H.', 'Chapman, Colin A.']",Sci Rep,,,True
5df25b46c3f42c20960c6e6e0caeb981b2f7759d,PMC,"Research progress on theaflavins: efficacy, formation, and preparation",http://dx.doi.org/10.1080/16546628.2017.1344521,PMC5510227,28747864,CC BY,"Background: Theaflavins (TFs) are a category of natural compounds characterized with the benzotropolone skeleton. The prominent benefits of TFs have been well documented. Amount of research were conducted and excellent achievements were disclosed during the past years. However, as far as we know, there is no comprehensive review about TFs. Scope and approach: This review summarized the recent research progress. The activity of TFs on anti-oxidation, anti-mutagenicity, hypolipidemic, anti-inflammatory, anti-cancer, anti-viral effect as well as the epidemiological cure were sorted. Converging pioneer literature and deduction, the underlying formation mechanism of TFs was proposed. Subsequently, acquisition of TFs was pointed out to be the fundament for further research. Accelerated by enzyme, bio-synthesis of TFs were reviewed simultaneously. At the end, employing modern analysis instrument and technology, isolations of TFs were enumerated. Key findings and conclusions: Structure of the skeleton as well as functional groups were paramount related with the bio-activity of TFs. Meanwhile, oxidation pathway of two catechin molecules to form TFs were hypothesized. Also, ascertainment of the several therapeutic efficiency of the family members of TFs would be the next step in the future.",2017 Jul 3,"He, Hua-Feng",Food Nutr Res,,,True
48adda1d8bd8fc96174dc65e1d51bc16820387f5,PMC,"Prevalence of respiratory viruses among adults, by season, age, respiratory tract region and type of medical unit in Paris, France, from 2011 to 2016",http://dx.doi.org/10.1371/journal.pone.0180888,PMC5510824,28708843,CC BY,"BACKGROUND: Multiplex PCR tests have improved our understanding of respiratory viruses’ epidemiology by allowing their wide range detection. We describe here the burden of these viruses in hospital settings over a five-year period. METHODS: All respiratory samples from adult patients (>20 years old) tested by multiplex-PCR at the request of physicians, from May 1 2011 to April 30 2016, were included retrospectively. Viral findings are reported by season, patient age group, respiratory tract region (upper or lower) and type of clinical unit (intensive care unit, pneumology unit, lung transplantation unit and other medical units). RESULTS: In total, 7196 samples (4958 patients) were included; 29.2% tested positive, with viral co-infections detected in 1.6% of samples. Overall, two viral groups accounted for 60.2% of all viruses identified: picornaviruses (rhinovirus or enterovirus, 34.3%) and influenza (26.6%). Influenza viruses constituted the group most frequently identified in winter (34.4%), in the upper respiratory tract (32%) and in patients over the age of 70 years (36.4%). Picornavirus was the second most frequently identified viral group in these populations and in all other groups, including lower respiratory tract infections (41.3%) or patients in intensive care units (37.6%). CONCLUSION: This study, the largest to date in Europe, provides a broad picture of the distribution of viruses over seasons, age groups, types of clinical unit and respiratory tract regions in the hospital setting. It highlights the burden associated with the neglected picornavirus group. These data have important implications for the future development of vaccines and antiviral drugs.",2017 Jul 14,"['Visseaux, Benoit', 'Burdet, Charles', 'Voiriot, Guillaume', 'Lescure, François-Xavier', 'Chougar, Taous', 'Brugière, Olivier', 'Crestani, Bruno', 'Casalino, Enrique', 'Charpentier, Charlotte', 'Descamps, Diane', 'Timsit, Jean-François', 'Yazdanpanah, Yazdan', 'Houhou-Fidouh, Nadhira']",PLoS One,,,True
11d016e4272c8a89fe7986afde61e6fb91908304,PMC,Nasopharyngeal microbiota in infants and changes during viral upper respiratory tract infection and acute otitis media,http://dx.doi.org/10.1371/journal.pone.0180630,PMC5510840,28708872,CC BY,"BACKGROUND: Interferences between pathogenic bacteria and specific commensals are known. We determined the interactions between nasopharyngeal microbial pathogens and commensals during viral upper respiratory tract infection (URI) and acute otitis media (AOM) in infants. METHODS: We analyzed 971 specimens collected monthly and during URI and AOM episodes from 139 infants. The 16S rRNA V4 gene regions were sequenced on the Illumina MiSeq platform. RESULTS: Among the high abundant genus-level nasopharyngeal microbiota were Moraxella, Haemophilus, and Streptococcus (3 otopathogen genera), Corynebacterium, Dolosigranulum, Staphylococcus, Acinetobacter, Pseudomonas, and Bifidobacterium. Bacterial diversity was lower in culture-positive samples for Streptococcus pneumoniae, and Haemophilus influenzae, compared to cultured-negative samples. URI frequencies were positively associated with increasing trend in otopathogen colonization. AOM frequencies were associated with decreasing trend in Micrococcus colonization. During URI and AOM, there were increases in abundance of otopathogen genera and decreases in Pseudomonas, Myroides, Yersinia, and Sphingomonas. Otopathogen abundance was increased during symptomatic viral infection, but not during asymptomatic infection. The risk for AOM complicating URI was reduced by increased abundance of Staphylococcus and Sphingobium. CONCLUSION: Otopathogen genera played the key roles in URI and AOM occurrences. Staphylococcus counteracts otopathogens thus Staphylococcal colonization may be beneficial, rather than harmful. While Sphingobium may play a role in preventing AOM complicating URI, the commonly used probiotic Bifidobacterium did not play a significant role during URI or AOM. The role of less common commensals in counteracting the deleterious effects of otopathogens requires further studies.",2017 Jul 14,"['Chonmaitree, Tasnee', 'Jennings, Kristofer', 'Golovko, Georgiy', 'Khanipov, Kamil', 'Pimenova, Maria', 'Patel, Janak A.', 'McCormick, David P.', 'Loeffelholz, Michael J.', 'Fofanov, Yuriy']",PLoS One,,,True
6080abc37c89429748cd5984f1d76f234f83eccf,PMC,Translating Big Data into Smart Data for Veterinary Epidemiology,http://dx.doi.org/10.3389/fvets.2017.00110,PMC5511962,28770216,CC BY,"The increasing availability and complexity of data has led to new opportunities and challenges in veterinary epidemiology around how to translate abundant, diverse, and rapidly growing “big” data into meaningful insights for animal health. Big data analytics are used to understand health risks and minimize the impact of adverse animal health issues through identifying high-risk populations, combining data or processes acting at multiple scales through epidemiological modeling approaches, and harnessing high velocity data to monitor animal health trends and detect emerging health threats. The advent of big data requires the incorporation of new skills into veterinary epidemiology training, including, for example, machine learning and coding, to prepare a new generation of scientists and practitioners to engage with big data. Establishing pipelines to analyze big data in near real-time is the next step for progressing from simply having “big data” to create “smart data,” with the objective of improving understanding of health risks, effectiveness of management and policy decisions, and ultimately preventing or at least minimizing the impact of adverse animal health issues.",2017 Jul 17,"['VanderWaal, Kimberly', 'Morrison, Robert B.', 'Neuhauser, Claudia', 'Vilalta, Carles', 'Perez, Andres M.']",Front Vet Sci,,,True
491a64ac4e81a8110aa76009bf9f6275712500bc,PMC,Evolutionary and genetic analysis of the VP2 gene of canine parvovirus,http://dx.doi.org/10.1186/s12864-017-3935-8,PMC5512735,28716118,CC BY,"BACKGROUND: Canine parvovirus (CPV) type 2 emerged in 1978 in the USA and quickly spread among dog populations all over the world with high morbidity. Although CPV is a DNA virus, its genomic substitution rate is similar to some RNA viruses. Therefore, it is important to trace the evolution of CPV to monitor the appearance of mutations that might affect vaccine effectiveness. RESULTS: Our analysis shows that the VP2 genes of CPV isolated from 1979 to 2016 are divided into six groups: GI, GII, GIII, GIV, GV, and GVI. Amino acid mutation analysis revealed several undiscovered important mutation sites: F267Y, Y324I, and T440A. Of note, the evolutionary rate of the CPV VP2 gene from Asia and Europe decreased. Codon usage analysis showed that the VP2 gene of CPV exhibits high bias with an ENC ranging from 34.93 to 36.7. Furthermore, we demonstrate that natural selection plays a major role compared to mutation pressure driving CPV evolution. CONCLUSIONS: There are few studies on the codon usage of CPV. Here, we comprehensively studied the genetic evolution, codon usage pattern, and evolutionary characterization of the VP2 gene of CPV. The novel findings revealing the evolutionary process of CPV will greatly serve future CPV research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3935-8) contains supplementary material, which is available to authorized users.",2017 Jul 17,"['Li, Gairu', 'Ji, Senlin', 'Zhai, Xiaofeng', 'Zhang, Yuxiang', 'Liu, Jie', 'Zhu, Mengyan', 'Zhou, Jiyong', 'Su, Shuo']",BMC Genomics,,,True
e659993cca4cf1cc40900a6625576e8c63013602,PMC,"The clinical and virological features of the first imported case causing MERS-CoV outbreak in South Korea, 2015",http://dx.doi.org/10.1186/s12879-017-2576-5,PMC5512736,28709419,CC BY,"BACKGROUND: In 2015, the largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection outside the Middle East occurred in South Korea. We summarized the epidemiological, clinical, and laboratory findings of the first Korean case of MERS-CoV and analyzed whole-genome sequences of MERS-CoV derived from the patient. CASE PRESENTATION: A 68-year-old man developed fever and myalgia 7 days after returning to Korea, following a 10-day trip to the Middle East. Before diagnosis, he visited 4 hospitals, potentially resulting in secondary transmission to 28 patients. On admission to the National Medical Center (day 9, post-onset of clinical illness), he presented with drowsiness, hypoxia, and multiple patchy infiltrations on the chest radiograph. He was intubated (day 12) because of progressive acute respiratory distress syndrome (ARDS) and INF-α2a and ribavirin treatment was commenced. The treatment course was prolonged by superimposed ventilator associated pneumonia. MERS-CoV PCR results converted to negative from day 47 and the patient was discharged (day 137), following rehabilitation therapy. The complete genome sequence obtained from a sputum sample (taken on day 11) showed the highest sequence similarity (99.59%) with the virus from an outbreak in Riyadh, Saudi Arabia, in February 2015. CONCLUSIONS: The first case of MERS-CoV infection had high transmissibility and was associated with a severe clinical course. The patient made a successful recovery after early treatment with antiviral agents and adequate supportive care. This first case in South Korea became a super-spreader because of improper infection control measures, rather than variations of the virus.",2017 Jul 14,"['Lee, Ji Yeon', 'Kim, You-Jin', 'Chung, Eun Hee', 'Kim, Dae-Won', 'Jeong, Ina', 'Kim, Yeonjae', 'Yun, Mi-ran', 'Kim, Sung Soon', 'Kim, Gayeon', 'Joh, Joon-Sung']",BMC Infect Dis,,,True
9ea62d48ba2e9f9c122aa34759f9bcb5451a09f4,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,True
8aa8e00dcc9541095e1d3d736ec5881385a26721,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
918212b7bbcdb7c6186394d3733455b309a4894a,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
2c4ece28d9439487cfadadec69902a7271d02306,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
0febce6585a81b6c4472e80af07096c90dc0fd27,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
4ae00e266df423463245d32d844c1584ca302922,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
f4a60d4e80172beadfa093bf5f363c6dc6ebf6b9,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
1bc21c27c3fd289440317b82f78e952c8930530c,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
ac2a6f872a003f492d446739495ab9b96a5fc04c,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
61dd2badcee64ed3c084719d2c3af68dc6450741,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
ee0b2fad200a6caeebd88e63030149896bda4170,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
020f3d44e81efe70666582bec244d097c32d699f,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
fcf98deb6b3f49067557632f82d63053bed3f61c,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
5d62c62d781ad62ef36b08c61cb509caa8de550b,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
4a47f30c975da78c2af43adabc6eb249d770563f,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
79afc680cdfb7ae18f2acd58c6e22585a5b2144a,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
1d33e716a98f6caa4d278289d0b90e7210a163d1,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
d761d40e2bc6a2227f17087cf3cc624e1b3620a2,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
96ae88d11e97ea80d04bdc7097a6f6a57cae704a,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
ed437ca7e40c57b5dd02dea1b7f11fa221590b60,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
24a9f4c6226b0e98ccfed5d69623296b685cef94,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
af848b6476cd1eef77759ab503efe6e64c65380c,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
3cc9af75ddb5dc18e0286c00d62eade0483d9c74,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
7dc4e6909aa4e4fb78fd2c18b7edba02462e7262,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
8b2c8df12cfffcd0eddb30bbb3858becff1dcdd5,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
a565fb8beaf3bda94b648bc1c1640cdd28a1dfab,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
b4e111cd2f52f1c052bfa919b8b7723e51f20c20,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
2dc06485aa5759a8d62a6ce1f40beae822eb21a4,PMC,Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study,http://dx.doi.org/10.1371/journal.pone.0181227,PMC5513450,28715489,CC BY,"The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.",2017 Jul 17,"['Bédubourg, Gabriel', 'Le Strat, Yann']",PLoS One,,,False
971794b30f2ec41a9c9708c25873f3cf55129518,PMC,"Phylogenic analysis of human bocavirus detected in children with acute respiratory infection in Yaounde, Cameroon",http://dx.doi.org/10.1186/s13104-017-2620-y,PMC5514512,28716110,CC BY,"OBJECTIVE: Human Bocavirus (HBoV) was first identified in 2005 and has been shown to be a common cause of respiratory infections and gastroenteritis in children. In a recent study, we found that 10.7% of children with acute respiratory infections (ARI) were infected by HBoV. Genetic characterization of this virus remains unknown in Central Africa, particularly in Cameroon Leeding us to evaluate the molecular characteristics of HBoV strains in Cameroonian children with ARI. RESULTS: Phylogenetic analysis of partial HBoV VP1/2 sequences showed a low level of nucleotide variation and the circulation of HBoV genotype 1 (HBoV-1) only. Three clades were obtained, two clustering with each of the reference strains ST1 and ST2, and a third group consisting of only Cameroon strains. By comparing with the Swedish reference sequences, ST1 and ST2, Cameroon sequences showed nucleotide and amino acid similarities of respectively 97.36–100% and 98.35–100%. These results could help improve strategies for monitoring and control of respiratory infections in Cameroon.",2017 Jul 17,"['Kenmoe, Sebastien', 'Vernet, Marie-Astrid', 'Njankouo-Ripa, Mohamadou', 'Penlap, Véronique Beng', 'Vabret, Astrid', 'Njouom, Richard']",BMC Res Notes,,,True
5f9daea45653f753380db839c7320be13dd2cbc4,PMC,Sepsis due to Streptococcus pneumoniae associated with secondary hemophagocytic lymphohistiocytosis in a splenectomized patient for spherocytosis: A case report,http://dx.doi.org/10.1097/MD.0000000000007520,PMC5515777,28700505,CC BY,"RATIONALE: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome that is characterized by an inappropriate hyperinflammatory immune response – primary, as a consequence of a genetic defect of NK cells and cytotoxic T lymphocytes or – secondary, in the progression of infections, rheumatic or autoimmune diseases, malignancies or metabolic diseases. PATIENT CONCERNS: We present the case of a secondary HLH due to Streptococcus pneumoniae infection in a splenectomised patient for spherocytosis, a 37-year-old patient who was splenectomised in childhood for spherocytosis, without immuneprophylaxis induced by antipneumococcal vaccine. OUTCOMES: He developed a severe pneumococcal sepsis associated with secondary HLH, with unfavorable outcome and death. LESSONS: To our knowledge, just 2 similar cases had been published in the literature, none in which the secondary HLH was the consequence of an invasive pneumococcal infection in a splenectomized patient for spherocytosis, and the association of splenectomy with HLH is surprizin.",2017 Jul 14,"['Birlutiu, Victoria', 'Birlutiu, Rares Mircea']",Medicine (Baltimore),,,True
fe21ba849b0dec6b69010568e1c16d39cdc45e3e,PMC,Coronavirus nucleocapsid proteins assemble constitutively in high molecular oligomers,http://dx.doi.org/10.1038/s41598-017-06062-w,PMC5515880,28720894,CC BY,"Coronaviruses (CoV) are enveloped viruses and rely on their nucleocapsid N protein to incorporate the positive-stranded genomic RNA into the virions. CoV N proteins form oligomers but the mechanism and relevance underlying their multimerization remain to be fully understood. Using in vitro pull-down experiments and density glycerol gradients, we found that at least 3 regions distributed over its entire length mediate the self-interaction of mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV) N protein. The fact that these regions can bind reciprocally between themselves provides a possible molecular basis for N protein oligomerization. Interestingly, cytoplasmic N molecules of MHV-infected cells constitutively assemble into oligomers through a process that does not require binding to genomic RNA. Based on our data, we propose a model where constitutive N protein oligomerization allows the optimal loading of the genomic viral RNA into a ribonucleoprotein complex via the presentation of multiple viral RNA binding motifs.",2017 Jul 18,"['Cong, Yingying', 'Kriegenburg, Franziska', 'de Haan, Cornelis A. M.', 'Reggiori, Fulvio']",Sci Rep,,,False
d73750cd7f032ab3f9fe5cf6f9a861c9e7567289,PMC,Coronavirus nucleocapsid proteins assemble constitutively in high molecular oligomers,http://dx.doi.org/10.1038/s41598-017-06062-w,PMC5515880,28720894,CC BY,"Coronaviruses (CoV) are enveloped viruses and rely on their nucleocapsid N protein to incorporate the positive-stranded genomic RNA into the virions. CoV N proteins form oligomers but the mechanism and relevance underlying their multimerization remain to be fully understood. Using in vitro pull-down experiments and density glycerol gradients, we found that at least 3 regions distributed over its entire length mediate the self-interaction of mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV) N protein. The fact that these regions can bind reciprocally between themselves provides a possible molecular basis for N protein oligomerization. Interestingly, cytoplasmic N molecules of MHV-infected cells constitutively assemble into oligomers through a process that does not require binding to genomic RNA. Based on our data, we propose a model where constitutive N protein oligomerization allows the optimal loading of the genomic viral RNA into a ribonucleoprotein complex via the presentation of multiple viral RNA binding motifs.",2017 Jul 18,"['Cong, Yingying', 'Kriegenburg, Franziska', 'de Haan, Cornelis A. M.', 'Reggiori, Fulvio']",Sci Rep,,,True
5db55ca30b7fcee9680f14af1a16d19df1bb0ea3,PMC,Mapping and characterization of G-quadruplexes in Mycobacterium tuberculosis gene promoter regions,http://dx.doi.org/10.1038/s41598-017-05867-z,PMC5515968,28720801,CC BY,"Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), one of the top 10 causes of death worldwide in 2015. The recent emergence of strains resistant to all current drugs urges the development of compounds with new mechanisms of action. G-quadruplexes are nucleic acids secondary structures that may form in G-rich regions to epigenetically regulate cellular functions. Here we implemented a computational tool to scan the presence of putative G-quadruplex forming sequences in the genome of Mycobacterium tuberculosis and analyse their association to transcription start sites. We found that the most stable G-quadruplexes were in the promoter region of genes belonging to definite functional categories. Actual G-quadruplex folding of four selected sequences was assessed by biophysical and biomolecular techniques: all molecules formed stable G-quadruplexes, which were further stabilized by two G-quadruplex ligands. These compounds inhibited Mycobacterium tuberculosis growth with minimal inhibitory concentrations in the low micromolar range. These data support formation of Mycobacterium tuberculosis G-quadruplexes in vivo and their potential regulation of gene transcription, and prompt the use of G4 ligands to develop original antitubercular agents.",2017 Jul 18,"['Perrone, Rosalba', 'Lavezzo, Enrico', 'Riello, Erika', 'Manganelli, Riccardo', 'Palù, Giorgio', 'Toppo, Stefano', 'Provvedi, Roberta', 'Richter, Sara N.']",Sci Rep,,,False
83f6440ed5fdcf297d2728df93830c842076c33c,PMC,Mapping and characterization of G-quadruplexes in Mycobacterium tuberculosis gene promoter regions,http://dx.doi.org/10.1038/s41598-017-05867-z,PMC5515968,28720801,CC BY,"Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), one of the top 10 causes of death worldwide in 2015. The recent emergence of strains resistant to all current drugs urges the development of compounds with new mechanisms of action. G-quadruplexes are nucleic acids secondary structures that may form in G-rich regions to epigenetically regulate cellular functions. Here we implemented a computational tool to scan the presence of putative G-quadruplex forming sequences in the genome of Mycobacterium tuberculosis and analyse their association to transcription start sites. We found that the most stable G-quadruplexes were in the promoter region of genes belonging to definite functional categories. Actual G-quadruplex folding of four selected sequences was assessed by biophysical and biomolecular techniques: all molecules formed stable G-quadruplexes, which were further stabilized by two G-quadruplex ligands. These compounds inhibited Mycobacterium tuberculosis growth with minimal inhibitory concentrations in the low micromolar range. These data support formation of Mycobacterium tuberculosis G-quadruplexes in vivo and their potential regulation of gene transcription, and prompt the use of G4 ligands to develop original antitubercular agents.",2017 Jul 18,"['Perrone, Rosalba', 'Lavezzo, Enrico', 'Riello, Erika', 'Manganelli, Riccardo', 'Palù, Giorgio', 'Toppo, Stefano', 'Provvedi, Roberta', 'Richter, Sara N.']",Sci Rep,,,True
4e40f15493a3858973a18ef28a6f533926167e81,PMC,Interaction of Influenza A Viruses with Oviduct Explants of Different Avian Species,http://dx.doi.org/10.3389/fmicb.2017.01338,PMC5518544,28775714,CC BY,"Infection of poultry with low pathogenic avian influenza viruses (LPAIV) is often associated with mild respiratory symptoms but may also lead to loss in egg production in laying birds. In vivo susceptibility of the reproductive tract for LPAIV infection was reported for turkeys and chickens, but virus-interaction with epithelial cells of the oviduct and possible stimulation of the local antiviral immune responses have not been characterized. In this study, we wanted to investigate the suitability of magnum organ cultures (MOC) as an in vitro model to study virus-host interactions. We compared the susceptibility of duck (Du), chicken (Ch), and turkey (Tu) MOC for three different influenza A viruses (IAV). Overall, the course of infection and the antiviral immune response varied between strains as well as host cell origin, but MOC gave reproducible results for all investigated parameters within each species. While pandemic (p) H1N1 and H9N2 efficiently replicated in MOC-Ch and MOC-Tu, MOC-Du were significantly less susceptible to infection as indicated by a reduced replication level for both viruses (p < 0.05). Overall, virus replication levels did not correlate with interferonα (IFNα) mRNA-expression levels in neither species. H9N2-infection led to a significant upregulation of interferonλ (IFNλ) mRNA expression in MOC of all species compared to the non-infected controls (p < 0.05), while a correlation with replication levels was only seen for MOC-Tu. pH1N1-infection induced only significant upregulation of IFNλ mRNA expression in MOC-Tu at 48 hours post infection (p < 0.05), but the expression pattern did not correlate with replication levels. Our results show that MOC are a suitable model to study IAV-interaction with the mucosal surface of the avian reproductive tract. The data suggest that the reproductive tract may play a role in the pathobiology of IAV in poultry.",2017 Jul 20,"['Sid, Hicham', 'Hartmann, Sandra', 'Winter, Christine', 'Rautenschlein, Silke']",Front Microbiol,,,True
a7fa116862ab1522f6ccbe6c261e83722fca138b,PMC,Role of fomites in SARS transmission during the largest hospital outbreak in Hong Kong,http://dx.doi.org/10.1371/journal.pone.0181558,PMC5519164,28727803,CC BY,"The epidemic of severe acute respiratory syndrome (SARS) had a significant effect on global society in the early 2000s and the potential of its resurgence exists. Studies on the modes of transmission of SARS are limited though a number of outbreak studies have revealed the possible airborne route. To develop more specific and effective control strategies, we conducted a detailed mechanism-based investigation that explored the role of fomite transmission in the well-known Ward 8A outbreak. We considered three hypothetical transmission routes, i.e., the long-range airborne, fomite and combined routes, in 1,744 scenarios with combinations of some important parameters. A multi-agent model was used to predict the infection risk distributions of the three hypothetical routes. Model selection was carried out for different scenarios to compare the distributions of infection risk with that of the reported attack rates and select the hypotheses with the best fitness. Our results reveal that under the assumed conditions, the SARS coronavirus was most possible to have spread via the combined long-range airborne and fomite routes, and that the fomite route played a non-negligible role in the transmission.",2017 Jul 20,"['Xiao, Shenglan', 'Li, Yuguo', 'Wong, Tze-wai', 'Hui, David S. C.']",PLoS One,,,True
1ef024725b588f435abcc6c51189d14b223d24fa,PMC,"Multiomics analysis of the giant triton snail salivary gland, a crown-of-thorns starfish predator",http://dx.doi.org/10.1038/s41598-017-05974-x,PMC5519703,28729681,CC BY,"The giant triton snail (Charonia tritonis) is one of the few natural predators of the adult Crown-of-Thorns starfish (COTS), a corallivore that has been damaging to many reefs in the Indo-Pacific. Charonia species have large salivary glands (SGs) that are suspected to produce either a venom and/or sulphuric acid which can immobilize their prey and neutralize the intrinsic toxic properties of COTS. To date, there is little information on the types of toxins produced by tritons. In this paper, the predatory behaviour of the C. tritonis is described. Then, the C. tritonis SG, which itself is made up of an anterior lobe (AL) and posterior lobe (PL), was analyzed using an integrated transcriptomics and proteomics approach, to identify putative toxin- and feeding-related proteins. A de novo transcriptome database and in silico protein analysis predicts that ~3800 proteins have features consistent with being secreted. A gland-specific proteomics analysis confirmed the presence of numerous SG-AL and SG-PL proteins, including those with similarity to cysteine-rich venom proteins. Sulfuric acid biosynthesis enzymes were identified, specific to the SG-PL. Our analysis of the C. tritonis SG (AL and PL) has provided a deeper insight into the biomolecular toolkit used for predation and feeding by C. tritonis.",2017 Jul 20,"['Bose, U.', 'Wang, T.', 'Zhao, M.', 'Motti, C. A.', 'Hall, M. R.', 'Cummins, S. F.']",Sci Rep,,,True
0fb887acf88daa31d5ae2b7d176baf904d6c5dfc,PMC,Recombinant feline parvovirus infection of immunized tigers in central China,http://dx.doi.org/10.1038/emi.2017.25,PMC5520303,28588292,CC BY,,2017 Jun 7,"['Wang, Xingang', 'Li, Tongyi', 'Liu, Hongying', 'Du, Jimei', 'Zhou, Feng', 'Dong, Yanming', 'He, Xiuyuan', 'Li, Yongtao', 'Wang, Chuanqing']",Emerg Microbes Infect,,,True
d1c3da8411eed001028326eb33acfb6bcdac877c,PMC,Additional molecular testing of saliva specimens improves the detection of respiratory viruses,http://dx.doi.org/10.1038/emi.2017.35,PMC5520312,28588283,CC BY,"Emerging infectious diseases in humans are often caused by respiratory viruses such as pandemic or avian influenza viruses and novel coronaviruses. Microbiological testing for respiratory viruses is important for patient management, infection control and epidemiological studies. Nasopharyngeal specimens are frequently tested, but their sensitivity is suboptimal. This study evaluated the incremental benefit of testing respiratory viruses in expectorated saliva using molecular assays. A total of 258 hospitalized adult patients with suspected respiratory infections were included. Their expectorated saliva was collected without the use of any special devices. In the first cohort of 159 patients whose nasopharyngeal aspirates (NPAs) tested positive for respiratory viruses during routine testing, the viral load was measured using quantitative reverse transcription PCR. Seventeen percent of the patients (27/159) had higher viral loads in the saliva than in the NPA. The second cohort consisted of 99 patients whose NPAs tested negative for respiratory viruses using a direct immunofluorescence assay. Their NPA and saliva specimens were additionally tested using multiplex PCR. In these patients, the concordance rate by multiplex PCR between NPA and saliva was 83.8%. Multiplex PCR detected viruses in saliva samples from 16 patients, of which nine (56.3%) had at least one virus that was not detected in the NPA. Decisions on antiviral or isolation precautions would be affected by salivary testing in six patients. Although NPAs have high viral loads and remain the specimen of choice for most patients with respiratory virus infections, supplementary molecular testing of saliva can improve the clinical management of these patients.",2017 Jun 7,"['To, Kelvin KW', 'Lu, Lu', 'Yip, Cyril CY', 'Poon, Rosana WS', 'Fung, Ami MY', 'Cheng, Andrew', 'Lui, Daniel HK', 'Ho, Deborah TY', 'Hung, Ivan FN', 'Chan, Kwok-Hung', 'Yuen, Kwok-Yung']",Emerg Microbes Infect,,,True
a126c62ed8ff8781b618d13b3b1127fde81076f8,PMC,Comparative epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia and South Korea,http://dx.doi.org/10.1038/emi.2017.40,PMC5520315,28588290,CC BY,"MERS-CoV infection emerged in the Kingdom of Saudi Arabia (KSA) in 2012 and has spread to 26 countries. However, 80% of all cases have occurred in KSA. The largest outbreak outside KSA occurred in South Korea (SK) in 2015. In this report, we describe an epidemiological comparison of the two outbreaks. Data from 1299 cases in KSA (2012–2015) and 186 cases in SK (2015) were collected from publicly available resources, including FluTrackers, the World Health Organization (WHO) outbreak news and the Saudi MOH (MOH). Descriptive analysis, t-tests, Chi-square tests and binary logistic regression were conducted to compare demographic and other characteristics (comorbidity, contact history) of cases by nationality. Epidemic curves of the outbreaks were generated. The mean age of cases was 51 years in KSA and 54 years in SK. Older males (⩾70 years) were more likely to be infected or to die from MERS-CoV infection, and males exhibited increased rates of comorbidity in both countries. The epidemic pattern in KSA was more complex, with animal-to-human, human-to-human, nosocomial and unknown exposure, whereas the outbreak in SK was more clearly nosocomial. Of the 1186 MERS cases in KSA with reported risk factors, 158 (13.3%) cases were hospital associated compared with 175 (94.1%) in SK, and an increased proportion of cases with unknown exposure risk was found in KSA (710, 59.9%). In a globally connected world, travel is a risk factor for emerging infections, and health systems in all countries should implement better triage systems for potential imported cases of MERS-CoV to prevent large epidemics.",2017 Jun 7,"['Chen, Xin', 'Chughtai, Abrar Ahmad', 'Dyda, Amalie', 'MacIntyre, Chandini Raina']",Emerg Microbes Infect,,,True
ac14fff2effb225af96af173c6035a28b34fb507,PMC,"Longitudinal study of Middle East Respiratory Syndrome coronavirus infection in dromedary camel herds in Saudi Arabia, 2014–2015",http://dx.doi.org/10.1038/emi.2017.44,PMC5520318,28634355,CC BY,"Two herds of dromedary camels were longitudinally sampled with nasal and rectal swabs and serum, between September 2014 and May 2015, and the samples were tested for Middle East Respiratory Syndrome (MERS) coronavirus RNA and antibodies. Evidence of MERS-CoV infection was confirmed in one herd on the basis of detection of virus RNA in nasal swabs from three camels and significant increases in the antibody titers from three others. The three viruses were genetically identical, thus indicating introduction of a single virus into this herd. There was evidence of reinfection of camels that were previously seropositive, thus suggesting that prior infection does not provide complete immunity from reinfection, a finding that is relevant to camel vaccination strategies as a means to prevent zoonotic transmission.",2017 Jun 21,"['Hemida, Maged Gomaa', 'Alnaeem, Abdulmohsen', 'Chu, Daniel KW', 'Perera, Ranawaka APM', 'Chan, Samuel MS', 'Almathen, Faisal', 'Yau, Emily', 'Ng, Brian CY', 'Webby, Richard J', 'Poon, Leo LM', 'Peiris, Malik']",Emerg Microbes Infect,,,True
a2fc621a71cddf750d46902684501f5f18eba3a0,PMC,A novel neutralizing monoclonal antibody targeting the N-terminal domain of the MERS-CoV spike protein,http://dx.doi.org/10.1038/emi.2017.18,PMC5520482,28536429,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) has caused fatal infections, some through hospital-acquired transmission, in affected regions since its emergence in 2012. Although the virus is not pandemic among humans, it poses a great threat to public health due to its zoonotic origin. Thus, both preventative and therapeutic countermeasures are urgently needed. In this study, we discovered a panel of neutralizing monoclonal antibodies (mAbs) against MERS-CoV, which mapped to a wide range of regions on the spike (S) protein of the virus. In addition to mAbs with neutralizing epitopes located on the receptor-binding domain, one mAb, 5F9, which binds to the N-terminal domain (NTD) of the MERS-CoV S1 subunit, showed efficient neutralizing activity against the wild-type MERS-CoV strain EMC/2012, with a half maximal inhibitory concentration of 0.2 μg/mL. We concluded that a novel neutralizing epitope for MERS-CoV also resides on the NTD of the S protein, indicating that the NTD might be important during the viral infection process. Our findings have significant implications for further vaccine design and for the development of prophylactic and therapeutic monoclonal immunotherapies against MERS-CoV infection.",2017 May 24,"['Chen, Yingzhu', 'Lu, Shuai', 'Jia, Hao', 'Deng, Yao', 'Zhou, Jianfang', 'Huang, Baoying', 'Yu, Yueyang', 'Lan, Jiaming', 'Wang, Wenling', 'Lou, Yongliang', 'Qin, Kun', 'Tan, Wenjie']",Emerg Microbes Infect,,,True
cde903001c25e2e1da0870eb9e40573e9fd8c424,PMC,Aging Does Not Affect Axon Initial Segment Structure and Somatic Localization of Tau Protein in Hippocampal Neurons of Fischer 344 Rats,http://dx.doi.org/10.1523/ENEURO.0043-17.2017,PMC5520750,28785724,CC BY,"Little is known about the specific contributions of aging to the neuron dysfunction and death in Alzheimer’s disease (AD). AD is characterized by the pathological accumulation of abnormal tau (a microtubule-associated protein), and the mislocalization of tau from the axon to the somatodendritic compartment is thought to play an important role in disease pathogenesis. The axon initial segment (AIS) is thought to play a role in the selective localization of tau in the axonal compartment. Thus, disruption in the AIS barrier may allow tau to diffuse freely back into the somatodendritic compartment and potentially lead to neurotoxicity. Here, we analyzed AISs using stereological methods and protein immunoblotting, and the localization of tau was assessed with immunofluorescence optical density measurements and protein immunoblotting. None of the outcome measurements assessed, including AIS structure, AIS protein levels, the distribution of tau in neurons of the hippocampus (HP), and total tau or phospho-tau protein levels were different in young, middle-, and old-age Fischer 344 rats. The outcome measurements assessed, including AIS structure, AIS protein levels, the distribution of tau in neurons of the HP, and total tau or phospho-tau protein levels were not different in young, middle-, and old-age Fischer 344 rats, with the exception of a small reduction in AIS volume and diameter in the CA2 region of aged animals. These data suggest that aging largely has no effect on these properties of the AIS or tau distribution, and thus, may not contribute directly to tau mislocalization.",2017 Jul 21,"['Kneynsberg, Andrew', 'Kanaan, Nicholas M.']",eNeuro,,,True
ac476cee9fb4aca11b589ea119a527db34398453,PMC,Dysregulation of pulmonary endothelial protein C receptor and thrombomodulin in severe falciparum malaria-associated ARDS relevant to hemozoin,http://dx.doi.org/10.1371/journal.pone.0181674,PMC5521846,28732053,CC0,"To investigate the role of the protein C system, endothelial protein C receptor (EPCR) and thrombomodulin (TM) in the pathogenesis of malaria-associated acute respiratory distress syndrome (ARDS) in relation to hemozoin and proinflammatory cytokines-induced type II pneumocyte injury and -aggravated pulmonary resolution. A total of 29 left-over lung specimens that were obtained from patients who died from severe falciparum malaria were examined. Histopathological, immunohistochemical and electron microscopic analyses revealed that ARDS coexisted with pulmonary edema and systemic bleeding; the severity was dependent on the level of hemozoin deposition in the lung and internal alveolar hemorrhaging. The loss of EPCR and TM was primarily identified in ARDS patients and was related to the level of hemozoin, parasitized red blood cell (PRBC) and white blood cell accumulation in the lung. Moreover, an in vitro analysis demonstrated that interleukin-13 and -31 and hemozoin induced pneumocytic cell injury and apoptosis, as assessed by EB/AO staining, electron microscopy and the up-regulation of CARD-9 mRNA (caspase recruitment domain-9 messenger-ribonucleic acid). The dysregulation of EPCR and TM in the lung, especially in those with increased levels of hemozoin, may play an important role in the pathogenesis of malaria-associated ARDS through an apoptotic pathway.",2017 Jul 21,"['Maknitikul, Sitang', 'Luplertlop, Natthanej', 'Grau, Georges E. R.', 'Ampawong, Sumate']",PLoS One,,,True
91eedbad589b474aad1ac0b96957078885146537,PMC,Differential expression of miR-195-5p in collapse of steroid-induced osteonecrosis of the femoral head,http://dx.doi.org/10.18632/oncotarget.17333,PMC5522094,28498798,CC BY,"BACKGROUND: Femoral head collapse is a key reference point for determining a treatment regimen of femoral head osteonecrosis. However, there are no effective preventive measures and the efficacy of hip-preserving surgery is unsatisfactory due to the unclear mechanism of collapse. This study aimed to identify and validate miRNAs differentially expressed in collapse and non-collapse areas of the osteonecrotic femoral head, and to predict the target genes and pathways of these miRNAs. RESULTS: Nine samples passed the quality control test. A total of 2085 differentially expressed miRNAs were detected, among which 433 miRNAs showed differential expression in the T1 group compared to the W1 group; 344 miRNAs showed differential expression in the T2 group compared to the W2 group; 107 miRNAs showed differential expression in the T3 group compared to the W3 group. After combining data from all three patients, 10 miRNAs showed differential expression in the collapse area (T1+T2+T3) compared to the non-collapse area (W1+W2+W3). Compared to the normal area, has-miR-195-5p showed the most significant downregulation. Expression results from RT-PCR revealed that the expression of hsa-miR-195-5p in the collapse area (T1+T2+T3) was significantly lower than that in the non-collapse area (W1+W2+W3) and normal area (Z1+Z2+Z3). 157 genes were perdicted as the target gene of hsa-miR-195-5p. MATERIALS AND METHODS: Femoral heads of three patients (2 males and 1 female) treated by total hip arthroplasty surgery for steroid-induced femoral head osteonecrosis were selected based on inclusion and exclusion criteria. Bone tissue samples were obtained from the collapse area (T), non-collapse area (W), and normal area (Z) according to the anatomical structure of osteonecrotic femoral heads. Total RNA was extracted from the samples and the microarray chip was scanned. miRNAs showing differential expressions of more than 1.5-fold were selected and was validated by RT-PCR. TargetScan, mirBase and miRanda bioinformatics software was used to predict target genes and identify possible pathways involving these genes. CONCLUSIONS: miR-195-5p showed the most significant difference in the collapse area of osteonecrotic femoral heads, suggesting that collapse may be related to the downregulation of miR-195-5p.",2017 Apr 21,"['Li, Pengfei', 'Zhai, Pei', 'Ye, Zengjie', 'Deng, Peng', 'Fan, Yueguang', 'Zeng, Yirong', 'Pang, Zhihui', 'Zeng, Jianchun', 'Li, Jie', 'Feng, Wenjun']",Oncotarget,,,True
c1111df73b989050bd7ffb92d274943ae5529777,PMC,Genome Sequence of Canine Polyomavirus in Respiratory Secretions of Dogs with Pneumonia of Unknown Etiology,http://dx.doi.org/10.1128/genomeA.00615-17,PMC5522929,28729262,CC BY,"We report here the first canine polyomavirus genome, identified by metagenomics in respiratory secretions of two dogs with severe pneumonia, which tested negative for all canine respiratory pathogens except Mycoplasma cynos. The isolate, Canis familiaris polyomavirus 1 (DogPyV-1), is a beta polyomavirus whose closest known LT antigen relatives are primate polyomaviruses.",2017 Jul 20,"['Delwart, Eric', 'Kapusinszky, Beatrix', 'Pesavento, Patricia A.', 'Estrada, Marko', 'Seguin, M. Alexis', 'Leutenegger, Christian M.']",Genome Announc,,,True
47dfb70a9174ea549a6850eb64223361ff14e597,PMC,Recombinant Tula hantavirus shows reduced fitness but is able to survive in the presence of a parental virus: analysis of consecutive passages in a cell culture,http://dx.doi.org/10.1186/1743-422X-2-12,PMC552329,15725355,CC BY,"Tula hantavirus carrying recombinant S RNA segment (recTULV) grew in a cell culture to the same titers as the original cell adapted variant but presented no real match to the parental virus. Our data showed that the lower competitiveness of recTULV could not be increased by pre-passaging in the cell culture. Nevertheless, the recombinant virus was able to survive in the presence of the parental virus during five consecutive passages. The observed survival time seems to be sufficient for transmission of newly formed recombinant hantaviruses in nature.",2005 Feb 22,"['Plyusnina, Angelina', 'Plyusnin, Alexander']",Virol J,,,True
85eb641e06b0d6b1a0b202275add0c5d27e53d71,PMC,Australia's international health relations in 2003,http://dx.doi.org/10.1186/1743-8462-2-3,PMC552331,15720728,CC BY,"A survey for the year 2003 of significant developments in Australia's official international health relations, and their domestic ramifications, is presented. The discussion is set within the broader context of Australian foreign policy. Sources include official documents, media reports and consultations with officers of the Department of Health and Ageing responsible for international linkages.",2005 Feb 21,"Barraclough, Simon",Aust New Zealand Health Policy,,,True
afc03cd8197cd7aa9e0ca665ebe6626c2a56ac4b,PMC,"Africa CDC: Establishing Integrated Surveillance and Laboratory Networks for Rapid Disease Detection and Response, Control, Prevention, and Clinical Care in Africa",http://dx.doi.org/10.4102/ajlm.v6i1.638,PMC5523921,28879156,CC BY,,2017 Jun 21,"Amukele, Timothy",Afr J Lab Med,,,True
6534f8468fbb6dbdaf078a9a59d92dc686a2c4b1,PMC,"A cell-based, quantitative and isoform-specific assay for exchange proteins directly activated by cAMP",http://dx.doi.org/10.1038/s41598-017-06432-4,PMC5524698,28740152,CC BY,"Extensive functional studies of the exchange protein directly activated by cAMP (EPAC) family of signaling molecules have demonstrated that EPAC proteins play a fundamental role in several physiological and pathophysiological responses, therefore are attractive drug targets. In this report, the development of a cell-based, medium to high throughput screening assay that is capable of monitoring EPAC-mediated activation of cellular Rap1 in an isoform-specific manner is described. This assay adapts a conventional ELISA format with immobilized RalGDS-RBD as a bait to selectively capture GTP-bound active Rap1. As a result, it fills an urgent need for a cell-based EPAC assay that can be conveniently performed using microtiter plates for the discovery and/or validation of isoform-specific EPAC agonists and antagonists.",2017 Jul 24,"['Zhu, Yingmin', 'Mei, Fang', 'Luo, Pei', 'Cheng, Xiaodong']",Sci Rep,,,True
d1c89147e1f62ad58bc92990ab797375e3aefd98,PMC,Human Zika infection induces a reduction of IFN-γ producing CD4 T-cells and a parallel expansion of effector Vδ2 T-cells,http://dx.doi.org/10.1038/s41598-017-06536-x,PMC5524759,28740159,CC BY,"The definition of the immunological response to Zika (ZIKV) infection in humans represents a key issue to identify protective profile useful for vaccine development and for pathogenesis studies. No data are available on the cellular immune response in the acute phase of human ZIKV infection, and its role in the protection and/or pathogenesis needs to be clarified. We studied and compared the phenotype and functionality of T-cells in patients with acute ZIKV and Dengue viral (DENV) infections. A significant activation of T-cells was observed during both ZIKV and DENV infections. ZIKV infection was characterized by a CD4 T cell differentiation toward effector cells and by a lower frequency of IFN-γ producing CD4 T cells. Moreover, a substantial expansion of CD3(+)CD4(−)CD8(−) T-cell subset expressing Vδ2 TCR was specifically observed in ZIKV patients. Vδ2 T cells presented a terminally differentiated profile, expressed granzyme B and maintained their ability to produce IFN-γ. These findings provide new knowledge on the immune response profile during self-limited infection that may help in vaccine efficacy definition, and in identifying possible immuno-pathogenetic mechanisms of severe infection.",2017 Jul 24,"['Cimini, Eleonora', 'Castilletti, Concetta', 'Sacchi, Alessandra', 'Casetti, Rita', 'Bordoni, Veronica', 'Romanelli, Antonella', 'Turchi, Federica', 'Martini, Federico', 'Tumino, Nicola', 'Nicastri, Emanuele', 'Corpolongo, Angela', 'Di Caro, Antonino', 'Kobinger, Gary', 'Zumla, Alimuddin', 'Capobianchi, Maria Rosaria', 'Ippolito, Giuseppe', 'Agrati, Chiara']",Sci Rep,,,True
fffaed7e9353b7df6c4ca8f66b62e117013cb86d,PMC,Dengue Virus Glycosylation: What Do We Know?,http://dx.doi.org/10.3389/fmicb.2017.01415,PMC5524768,28791003,CC BY,"In many infectious diseases caused by either viruses or bacteria, pathogen glycoproteins play important roles during the infection cycle, ranging from entry to successful intracellular replication and host immune evasion. Dengue is no exception. Dengue virus glycoproteins, envelope protein (E) and non-structural protein 1 (NS1) are two popular sub-unit vaccine candidates. E protein on the virion surface is the major target of neutralizing antibodies. NS1 which is secreted during DENV infection has been shown to induce a variety of host responses through its binding to several host factors. However, despite their critical role in disease and protection, the glycosylated variants of these two proteins and their biological importance have remained understudied. In this review, we seek to provide a comprehensive summary of the current knowledge on protein glycosylation in DENV, and its role in virus biogenesis, host cell receptor interaction and disease pathogenesis.",2017 Jul 25,"['Yap, Sally S. L.', 'Nguyen-Khuong, Terry', 'Rudd, Pauline M.', 'Alonso, Sylvie']",Front Microbiol,,,True
d6f98dfbb1173619d9b20b4c353a37c3d04f046d,PMC,"Replication of H9 influenza viruses in the human ex vivo respiratory tract, and the influence of neuraminidase on virus release",http://dx.doi.org/10.1038/s41598-017-05853-5,PMC5524967,28740108,CC BY,"H9N2 viruses are the most widespread influenza viruses in poultry in Asia. We evaluated the infection and tropism of human and avian H9 influenza virus in the human respiratory tract using ex vivo respiratory organ culture. H9 viruses infected the upper and lower respiratory tract and the majority of H9 viruses had a decreased ability to release virus from the bronchus rather than the lung. This may be attributed to a weak neuraminidase (NA) cleavage of carbon-6-linked sialic acid (Sia) rather than carbon-3-linked Sia. The modified cleavage of N-acetlylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) by NA in H9 virus replication was observed by reverse genetics, and recombinant H9N2 viruses with amino acids (38KQ) deleted in the NA stalk, and changing the amino acid at position 431 from Proline-to-Lysine. Using recombinant H9 viruses previously evaluated in the ferret, we found that viruses which replicated well in the ferret did not replicate to the same extent in the human ex vivo cultures. The existing risk assessment models for H9N2 viruses in ferrets may not always have a strong correlation with the replication in the human upper respiratory tract. The inclusion of the human ex vivo cultures would further strengthen the future risk-assessment strategies.",2017 Jul 24,"['Chan, Renee W. Y.', 'Chan, Louisa L. Y.', 'Mok, Chris K. P.', 'Lai, Jimmy', 'Tao, Kin P.', 'Obadan, Adebimpe', 'Chan, Michael C. W.', 'Perez, Daniel R.', 'Peiris, J. S. Malik', 'Nicholls, John M.']",Sci Rep,,,False
d2ac1b9fae19dbf111222f50982b4ed38e2f8e28,PMC,"Replication of H9 influenza viruses in the human ex vivo respiratory tract, and the influence of neuraminidase on virus release",http://dx.doi.org/10.1038/s41598-017-05853-5,PMC5524967,28740108,CC BY,"H9N2 viruses are the most widespread influenza viruses in poultry in Asia. We evaluated the infection and tropism of human and avian H9 influenza virus in the human respiratory tract using ex vivo respiratory organ culture. H9 viruses infected the upper and lower respiratory tract and the majority of H9 viruses had a decreased ability to release virus from the bronchus rather than the lung. This may be attributed to a weak neuraminidase (NA) cleavage of carbon-6-linked sialic acid (Sia) rather than carbon-3-linked Sia. The modified cleavage of N-acetlylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) by NA in H9 virus replication was observed by reverse genetics, and recombinant H9N2 viruses with amino acids (38KQ) deleted in the NA stalk, and changing the amino acid at position 431 from Proline-to-Lysine. Using recombinant H9 viruses previously evaluated in the ferret, we found that viruses which replicated well in the ferret did not replicate to the same extent in the human ex vivo cultures. The existing risk assessment models for H9N2 viruses in ferrets may not always have a strong correlation with the replication in the human upper respiratory tract. The inclusion of the human ex vivo cultures would further strengthen the future risk-assessment strategies.",2017 Jul 24,"['Chan, Renee W. Y.', 'Chan, Louisa L. Y.', 'Mok, Chris K. P.', 'Lai, Jimmy', 'Tao, Kin P.', 'Obadan, Adebimpe', 'Chan, Michael C. W.', 'Perez, Daniel R.', 'Peiris, J. S. Malik', 'Nicholls, John M.']",Sci Rep,,,True
5d1257333598094fd630f16f989336a2c5d223a9,PMC,Necrotizing pneumonia: an emerging problem in children?,http://dx.doi.org/10.1186/s41479-017-0035-0,PMC5525269,28770121,CC BY,"BACKGROUND: In children, necrotizing pneumonia (NP) is an uncommon, severe complication of pneumonia. It is characterized by destruction of the underlying lung parenchyma resulting in multiple small, thin-walled cavities and is often accompanied by empyema and bronchopleural fistulae. REVIEW: NP in children was first reported in children in 1994, and since then there has been a gradual increase in cases, which is partially explained by greater physician awareness and use of contrast computed tomography (CT) scans, and by temporal changes in circulating respiratory pathogens and antibiotic prescribing. The most common pathogens detected in children with NP are pneumococci and Staphylococcus aureus. The underlying disease mechanisms are poorly understood, but likely relate to multiple host susceptibility and bacterial virulence factors, with viral–bacterial interactions also possibly having a role. Most cases are in previously healthy young children who, despite adequate antibiotic therapy for bacterial pneumonia, remain febrile and unwell. Many also have evidence of pleural effusion, empyema, or pyopneumothorax, which has undergone drainage or surgical intervention without clinical improvement. The diagnosis is generally made by chest imaging, with CT scans being the most sensitive, showing loss of normal pulmonary architecture, decreased parenchymal enhancement and multiple thin-walled cavities. Blood culture and culture and molecular testing of pleural fluid provide a microbiologic diagnosis in as many as 50% of cases. Prolonged antibiotics, draining pleural fluid and gas that causes mass effects, and maintaining ventilation, circulation, nutrition, fluid, and electrolyte balance are critical components of therapy. Despite its serious nature, death is uncommon, with good clinical, radiographic and functional recovery achieved in the 5–6 months following diagnosis. Increased knowledge of NP’s pathogenesis will assist more rapid diagnosis and improve treatment and, ultimately, prevention. CONCLUSION: It is important to consider that our understanding of NP is limited to individual case reports or small case series, and treatment data from randomized-controlled trials are lacking. Furthermore, case series are retrospective and usually confined to single centers. Consequently, these studies may not be representative of patients in other locations, especially when allowing for temporal changes in pathogen behaviour and differences in immunization schedules and antibiotic prescribing practices.",2017 Jul 25,"['Masters, I. Brent', 'Isles, Alan F.', 'Grimwood, Keith']",Pneumonia (Nathan),,,True
fcd0b20d3b55d4c5029f98c3612ff577394ebf3d,PMC,Highly suspected cases of salmonellosis in two cats fed with a commercial raw meat-based diet: health risks to animals and zoonotic implications,http://dx.doi.org/10.1186/s12917-017-1143-z,PMC5525297,28738871,CC BY,"BACKGROUND: Feeding raw meat-based diets (RMBD) to companion animals raises public health concerns for both animals and humans. While considerable attention has been paid to bacterial contamination of commercial pet food, few literature studies have investigated foodborne disease in companion animals. Salmonellosis is reported to be infrequent in cats but no known data or studies estimating feline salmonellosis are available or large-scale epidemiological studies assessing Salmonella risk factors. CASE PRESENTATION: Two highly suspected cases of salmonellosis in two cats fed with a commercial frozen poultry RMBD are presented, for the first time from the same household. The clinical presentation, diagnostics, treatment and follow-up are reported and the zoonotic implications are discussed. CONCLUSIONS: This case highlights the health risks posed to both animals and owners by feeding RMBD to pets, and suggests that these risks should be considered by veterinary practitioners.",2017 Jul 24,"['Giacometti, Federica', 'Magarotto, Jacopo', 'Serraino, Andrea', 'Piva, Silvia']",BMC Vet Res,,,True
c1903895a3fc53a43a81d310f7567181bdee782f,PMC,"New hydrazonoindolin-2-ones: Synthesis, exploration of the possible anti-proliferative mechanism of action and encapsulation into PLGA microspheres",http://dx.doi.org/10.1371/journal.pone.0181241,PMC5526551,28742842,CC BY,"The synthesis and molecular characterization of new isatin-based hydrazonoindolin-2-ones 4a-o and 7a-e are reported. The in vitro anti-proliferative potential of the synthesized compounds 4a-o and 7a-e was examined against HT-29 (colon), ZR-75 (breast) and A549 (lung) human cancer cell lines. Compounds 7b, 7d and 7e were the most active congeners against the tested human cancer cell lines with average IC(50) values of 4.77, 3.39 and 2.37 μM, respectively, as compared with the reference isatin-based drug, sunitinib, which exhibited an average IC(50) value of 8.11 μM. Compound 7e was selected for further pharmacological evaluation in order to gain insight into its possible mechanism of action. It increased caspase 3/7 activity by 2.4- and 1.85-fold between 4 and 8 h of treatment, respectively, at 10 μM and it caused a decrease in the percentage of cells in the G1 phase of the cell cycle with a corresponding increase in the S-phase. In addition, compound 7e increased phosphorylated tyrosine (p-Tyr) levels nearly two-fold with an apparent IC(50) value of 3.8 μM. The 7e-loaded PLGA microspheres were prepared using a modified emulsion-solvent diffusion method. The average encapsulation efficiency of the 7e-loaded PLGA microspheres was 85% ± 1.3. While, the in vitro release profile of the 7e-loaded microspheres was characterized by slow and continuous release of compound 7e during 21 days and the release curve was fitted to zero order kinetics. Incorporation of 7e into PLGA microspheres improved its in vitro anti-proliferative activity toward the human cancer cell line A549 after 120 h incubation period with an IC(50) value less than 0.8 μM.",2017 Jul 25,"['Attia, Mohamed I.', 'Eldehna, Wagdy M.', 'Afifi, Samar A.', 'Keeton, Adam B.', 'Piazza, Gary A.', 'Abdel-Aziz, Hatem A.']",PLoS One,,,True
7bdb190c3d2ae6cbc892c98951346220b168d4e7,PMC,A comparison study between GeXP-based multiplex-PCR and serology assay for Mycoplasma pneumoniae detection in children with community acquired pneumonia,http://dx.doi.org/10.1186/s12879-017-2614-3,PMC5527399,28743259,CC BY,"BACKGROUND: Diagnosis of community-acquired pneumonia (CAP) caused by Mycoplasma pneumoniae (Mp) in children has been hampered by difficulty in obtaining convalescent serum and time constraints. In this study, the two diagnostic assays that targeted respectively on Mp-antibody and Mp-DNA were retrospectively investigated. METHODS: A total of 3146 children were clinically diagnosed to have CAP and were confirmed by chest X-ray during March 2015 to February 2016 in Children’s hospital of Hebei Province (China). Both of the sera and sputum samples were collected in 24 h after their admission. The Mp-antibody was examined by the passive particle agglutination assay and a fourfold or greater increase of antibody titers of paired sera or≧1:160 titer of single serum was set as the serology positive. Mp-DNA in the sputum samples was tested by a multiplex-PCR method named GeXP assay (multiplex PCR combined with automated capillary electrophoresis). In order to eliminate the false positive results caused by the asymptomatic carriage after infected by M. pneumoniae, the inconsistent samples were tested by the real-time isothermal transcription-mediated RNA amplification assay (SAT). RESULTS: The inter-rated agreement test was performed in 3146 CAP patients, with a highest kappa value in the school-age children as 0.783. There were 6.29% (198/3146) cases showed inconsistent results determined by GeXP and serology assay. All of the 19 GeXP(+)/Serology (−) samples and a randomly chosen 27 from 179 GeXP(−)/Serology (+) samples were tested by SAT assay, and a 97.8% diagnosis agreement was observed between SAT and GeXP assay, but not with the serology assay. In addition, patients who were detected only by serology or only by multiplex-PCR were significantly younger than those with both methods positive (3.0 and 1.5 years vs. 5.0 years, p < 0.01). The Viral-Mp coinfection accounted for 37.0% (97/262), which was more common in winter and spring (p < 0.05) and in the infantile group (p < 0.01), compared to the pure Mp positive ones. CONCLUSION: In some children CAP cases, the Mp laboratory diagnosis was inconsistent between serology and multiplex-PCR assay. Verified by the SAT assay, the GeXP showed a more sensitive and reliable performance compared with the serology assay. Furthermore, employing the multiplex-PCR could provide more information on the associated pathogens for clinical assessment of CAP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-017-2614-3) contains supplementary material, which is available to authorized users.",2017 Jul 25,"['Wang, Le', 'Feng, Zhishan', 'Zhao, Mengchuan', 'Yang, Shuo', 'Yan, Xiaotong', 'Guo, Weiwei', 'Shi, Zhongren', 'Li, Guixia']",BMC Infect Dis,,,True
3f53b06b28618d70bbb7b13cdc1acb7d09dc21c1,PMC,Multimechanistic Monoclonal Antibodies (MAbs) Targeting Staphylococcus aureus Alpha-Toxin and Clumping Factor A: Activity and Efficacy Comparisons of a MAb Combination and an Engineered Bispecific Antibody Approach,http://dx.doi.org/10.1128/AAC.00629-17,PMC5527613,28584141,CC BY,"Secreted alpha-toxin and surface-localized clumping factor A (ClfA) are key virulence determinants in Staphylococcus aureus bloodstream infections. We previously demonstrated that prophylaxis with a multimechanistic monoclonal antibody (MAb) combination against alpha-toxin (MEDI4893*) and ClfA (11H10) provided greater strain coverage and improved efficacy in an S. aureus lethal bacteremia model. Subsequently, 11H10 was found to exhibit reduced affinity and impaired inhibition of fibrinogen binding to ClfA002 expressed by members of a predominant hospital-associated methicillin-resistant S. aureus (MRSA) clone, ST5. Consequently, we identified another anti-ClfA MAb (SAR114) from human tonsillar B cells with >100-fold increased affinity for three prominent ClfA variants, including ClfA002, and potent inhibition of bacterial agglutination by 112 diverse clinical isolates. We next constructed bispecific Abs (BiSAbs) comprised of 11H10 or SAR114 as IgG scaffolds and grafted anti-alpha-toxin (MEDI4893*) single-chain variable fragment to the amino or carboxy terminus of the anti-ClfA heavy chains. Although the BiSAbs exhibited in vitro potencies similar to those of the parental MAbs, only 11H10-BiSAb, but not SAR114-BiSAb, showed protective activity in murine infection models comparable to the respective MAb combination. In vivo activity with SAR114-BiSAb was observed in infection models with S. aureus lacking ClfA. Our data suggest that high-affinity binding to ClfA sequesters the SAR114-BiSAb to the bacterial surface, thereby reducing both alpha-toxin neutralization and protection in vivo. These results indicate that a MAb combination targeting ClfA and alpha-toxin is more promising for future development than the corresponding BiSAb.",2017 Jul 25,"['Tkaczyk, C.', 'Kasturirangan, S.', 'Minola, A.', 'Jones-Nelson, O.', 'Gunter, V.', 'Shi, Y. Y.', 'Rosenthal, K.', 'Aleti, V.', 'Semenova, E.', 'Warrener, P.', 'Tabor, D.', 'Stover, C. K.', 'Corti, D.', 'Rainey, G.', 'Sellman, B. R.']",Antimicrob Agents Chemother,,,False
29bdff5ccc8a7e0a2b20a3d1ed9354ed29c553a3,PMC,Multimechanistic Monoclonal Antibodies (MAbs) Targeting Staphylococcus aureus Alpha-Toxin and Clumping Factor A: Activity and Efficacy Comparisons of a MAb Combination and an Engineered Bispecific Antibody Approach,http://dx.doi.org/10.1128/AAC.00629-17,PMC5527613,28584141,CC BY,"Secreted alpha-toxin and surface-localized clumping factor A (ClfA) are key virulence determinants in Staphylococcus aureus bloodstream infections. We previously demonstrated that prophylaxis with a multimechanistic monoclonal antibody (MAb) combination against alpha-toxin (MEDI4893*) and ClfA (11H10) provided greater strain coverage and improved efficacy in an S. aureus lethal bacteremia model. Subsequently, 11H10 was found to exhibit reduced affinity and impaired inhibition of fibrinogen binding to ClfA002 expressed by members of a predominant hospital-associated methicillin-resistant S. aureus (MRSA) clone, ST5. Consequently, we identified another anti-ClfA MAb (SAR114) from human tonsillar B cells with >100-fold increased affinity for three prominent ClfA variants, including ClfA002, and potent inhibition of bacterial agglutination by 112 diverse clinical isolates. We next constructed bispecific Abs (BiSAbs) comprised of 11H10 or SAR114 as IgG scaffolds and grafted anti-alpha-toxin (MEDI4893*) single-chain variable fragment to the amino or carboxy terminus of the anti-ClfA heavy chains. Although the BiSAbs exhibited in vitro potencies similar to those of the parental MAbs, only 11H10-BiSAb, but not SAR114-BiSAb, showed protective activity in murine infection models comparable to the respective MAb combination. In vivo activity with SAR114-BiSAb was observed in infection models with S. aureus lacking ClfA. Our data suggest that high-affinity binding to ClfA sequesters the SAR114-BiSAb to the bacterial surface, thereby reducing both alpha-toxin neutralization and protection in vivo. These results indicate that a MAb combination targeting ClfA and alpha-toxin is more promising for future development than the corresponding BiSAb.",2017 Jul 25,"['Tkaczyk, C.', 'Kasturirangan, S.', 'Minola, A.', 'Jones-Nelson, O.', 'Gunter, V.', 'Shi, Y. Y.', 'Rosenthal, K.', 'Aleti, V.', 'Semenova, E.', 'Warrener, P.', 'Tabor, D.', 'Stover, C. K.', 'Corti, D.', 'Rainey, G.', 'Sellman, B. R.']",Antimicrob Agents Chemother,,,True
32011a9e06d16f2e8bf8f86977aaa8143e9fc692,PMC,Identification of one B-cell epitope from NS1 protein of duck Tembusu virus with monoclonal antibodies,http://dx.doi.org/10.1371/journal.pone.0181177,PMC5528836,28746401,CC BY,"This study describes the identification of one linear B-cell epitope on TMUV NS1 protein with monoclonal antibody (mAb) 3G2 by indirect enzyme-linked immunosorbent assay (ELISA). In this study, NS1 protein was expressed in prokaryotic expression system and purified. One mAb against NS1 protein was generated from Balb/c mice immunized with recombinant protein NS1. A set of 35 partially-overlapping polypeptides covering the entire NS1 protein was expressed with PGEX-6P-1 vector and screened with mAb 3G2. One polypeptide against the mAb was acquired and identified by indirect ELISA and western-blot. To map the epitope accurately, one or two amino acid residues were removed from the carboxy and amino terminal of polypeptide sequentially. A series of truncated oligopeptides were expressed and purified. The minimal determinant of the linear B cell epitope was recognized and identified with mAb 3G2. The accurate linear B-cell epitope was (269)DEKEIV(274) located in NS1 protein. Furthermore, sequence alignment showed that the epitope was highly conserved and specific among TMUV strains and other flavivirus respectively. The linear B-cell epitope of TMUV NS1 protein could benefit the development of new vaccines and diagnostic assays.",2017 Jul 26,"['Ti, Jinfeng', 'Li, Zhijie', 'Li, Xiuli', 'Lu, Yunjian', 'Diao, Youxiang', 'Li, Fang']",PLoS One,,,True
0f06fc59914545bf3fdd7ae0b2cd8fe2a4208ace,PMC,Effects of oxidative and thermal stresses on stress granule formation in human induced pluripotent stem cells,http://dx.doi.org/10.1371/journal.pone.0182059,PMC5528897,28746394,CC BY,"Stress Granules (SGs) are dynamic ribonucleoprotein aggregates, which have been observed in cells subjected to environmental stresses, such as oxidative stress and heat shock (HS). Although pluripotent stem cells (PSCs) are highly sensitive to oxidative stress, the role of SGs in regulating PSC self-renewal and differentiation has not been fully elucidated. Here we found that sodium arsenite (SA) and HS, but not hydrogen peroxide (H(2)O(2)), induce SG formation in human induced (hi) PSCs. Particularly, we found that these granules contain the well-known SG proteins (G3BP, TIAR, eIF4E, eIF4A, eIF3B, eIF4G, and PABP), were found in juxtaposition to processing bodies (PBs), and were disassembled after the removal of the stress. Moreover, we showed that SA and HS, but not H(2)O(2), promote eIF2α phosphorylation in hiPSCs forming SGs. Analysis of pluripotent protein expression showed that HS significantly reduced all tested markers (OCT4, SOX2, NANOG, KLF4, L1TD1, and LIN28A), while SA selectively reduced the expression levels of NANOG and L1TD1. Finally, in addition to LIN28A and L1TD1, we identified DPPA5 (pluripotent protein marker) as a novel component of SGs. Collectively, these results provide new insights into the molecular cues of hiPSCs responses to environmental insults.",2017 Jul 26,"['Palangi, Freshteh', 'Samuel, Samson M.', 'Thompson, I. Richard', 'Triggle, Chris R.', 'Emara, Mohamed M.']",PLoS One,,,True
32c84fee3ed37c2e6c75c620876421e7c68df330,PMC,Epidemiology and characterization of avian infectious bronchitis virus strains circulating in southern China during the period from 2013–2015,http://dx.doi.org/10.1038/s41598-017-06987-2,PMC5529424,28747730,CC BY,"Two hundred and six strains of avian infectious bronchitis virus (IBV) were isolated from chickens showing signs of disease in southern China during the period from 2013–2015. The nucleotide and amino acid sequences from the isolated field strains were compared to 42 published references. Nucleotide homologies ranged from 63.1–99.9% and amino acid homologies ranging from 60.2–100%. At least seven IBV genotypes were co-circulating in commercial chicken farms in southern China. The IBV isolates were genetically diverse and underwent continuing evolution. The QX-type, TW I-type, and 4/91-type were the most common genotypes during the three-year observation period and accounted for 88.8% of the isolated strains. Notably, the prevalence of the TW I-type strains has been increasing in recent years and has become the most common genotype in China. The emergence of variant IBV strains can be attributed to recombination. Serologic analysis and antigenic 3D cartography of 4 reference and 14 field isolated strains indicated the surveyed IBVs had diverse serology types and that the serotype of the isolated QX-type and TW I-type strains was distinct from the vaccines strains. Therefore, long-term continuing surveillance is necessary for IBV prevention and control.",2017 Jul 26,"['Feng, Keyu', 'Wang, Feng', 'Xue, Yu', 'Zhou, Qingfeng', 'Chen, Feng', 'Bi, Yingzuo', 'Xie, Qingmei']",Sci Rep,,,False
5808eac43f4ee06a648815a400aab4b73ee2d6b2,PMC,Epidemiology and characterization of avian infectious bronchitis virus strains circulating in southern China during the period from 2013–2015,http://dx.doi.org/10.1038/s41598-017-06987-2,PMC5529424,28747730,CC BY,"Two hundred and six strains of avian infectious bronchitis virus (IBV) were isolated from chickens showing signs of disease in southern China during the period from 2013–2015. The nucleotide and amino acid sequences from the isolated field strains were compared to 42 published references. Nucleotide homologies ranged from 63.1–99.9% and amino acid homologies ranging from 60.2–100%. At least seven IBV genotypes were co-circulating in commercial chicken farms in southern China. The IBV isolates were genetically diverse and underwent continuing evolution. The QX-type, TW I-type, and 4/91-type were the most common genotypes during the three-year observation period and accounted for 88.8% of the isolated strains. Notably, the prevalence of the TW I-type strains has been increasing in recent years and has become the most common genotype in China. The emergence of variant IBV strains can be attributed to recombination. Serologic analysis and antigenic 3D cartography of 4 reference and 14 field isolated strains indicated the surveyed IBVs had diverse serology types and that the serotype of the isolated QX-type and TW I-type strains was distinct from the vaccines strains. Therefore, long-term continuing surveillance is necessary for IBV prevention and control.",2017 Jul 26,"['Feng, Keyu', 'Wang, Feng', 'Xue, Yu', 'Zhou, Qingfeng', 'Chen, Feng', 'Bi, Yingzuo', 'Xie, Qingmei']",Sci Rep,,,True
76d7fe0354828411a05ec3846931ffdf23cfe1cf,PMC,Crystal structure of the receptor binding domain of the spike glycoprotein of human betacoronavirus HKU1,http://dx.doi.org/10.1038/ncomms15216,PMC5529671,28534504,CC BY,"Human coronavirus (CoV) HKU1 is a pathogen causing acute respiratory illnesses and so far little is known about its biology. HKU1 virus uses its S1 subunit C-terminal domain (CTD) and not the N-terminal domain like other lineage A β-CoVs to bind to its yet unknown human receptor. Here we present the crystal structure of HKU1 CTD at 1.9 Å resolution. The structure consists of three subdomains: core, insertion and subdomain-1 (SD-1). While the structure of the core and SD-1 subdomains of HKU1 are highly similar to those of other β-CoVs, the insertion subdomain adopts a novel fold, which is largely invisible in the cryo-EM structure of the HKU1 S trimer. We identify five residues in the insertion subdomain that are critical for binding of neutralizing antibodies and two residues essential for receptor binding. Our study contributes to a better understanding of entry, immunity and evolution of CoV S proteins.",2017 May 23,"['Ou, Xiuyuan', 'Guan, Hongxin', 'Qin, Bo', 'Mu, Zhixia', 'Wojdyla, Justyna A.', 'Wang, Meitian', 'Dominguez, Samuel R.', 'Qian, Zhaohui', 'Cui, Sheng']",Nat Commun,,,True
fd59786161c6f852a77338bc0cfe577bde28458c,PMC,Crystal structure of the receptor binding domain of the spike glycoprotein of human betacoronavirus HKU1,http://dx.doi.org/10.1038/ncomms15216,PMC5529671,28534504,CC BY,"Human coronavirus (CoV) HKU1 is a pathogen causing acute respiratory illnesses and so far little is known about its biology. HKU1 virus uses its S1 subunit C-terminal domain (CTD) and not the N-terminal domain like other lineage A β-CoVs to bind to its yet unknown human receptor. Here we present the crystal structure of HKU1 CTD at 1.9 Å resolution. The structure consists of three subdomains: core, insertion and subdomain-1 (SD-1). While the structure of the core and SD-1 subdomains of HKU1 are highly similar to those of other β-CoVs, the insertion subdomain adopts a novel fold, which is largely invisible in the cryo-EM structure of the HKU1 S trimer. We identify five residues in the insertion subdomain that are critical for binding of neutralizing antibodies and two residues essential for receptor binding. Our study contributes to a better understanding of entry, immunity and evolution of CoV S proteins.",2017 May 23,"['Ou, Xiuyuan', 'Guan, Hongxin', 'Qin, Bo', 'Mu, Zhixia', 'Wojdyla, Justyna A.', 'Wang, Meitian', 'Dominguez, Samuel R.', 'Qian, Zhaohui', 'Cui, Sheng']",Nat Commun,,,False
5252e99fc0d5155e6331c673d145e4450623112a,PMC,Crystal structure of the receptor binding domain of the spike glycoprotein of human betacoronavirus HKU1,http://dx.doi.org/10.1038/ncomms15216,PMC5529671,28534504,CC BY,"Human coronavirus (CoV) HKU1 is a pathogen causing acute respiratory illnesses and so far little is known about its biology. HKU1 virus uses its S1 subunit C-terminal domain (CTD) and not the N-terminal domain like other lineage A β-CoVs to bind to its yet unknown human receptor. Here we present the crystal structure of HKU1 CTD at 1.9 Å resolution. The structure consists of three subdomains: core, insertion and subdomain-1 (SD-1). While the structure of the core and SD-1 subdomains of HKU1 are highly similar to those of other β-CoVs, the insertion subdomain adopts a novel fold, which is largely invisible in the cryo-EM structure of the HKU1 S trimer. We identify five residues in the insertion subdomain that are critical for binding of neutralizing antibodies and two residues essential for receptor binding. Our study contributes to a better understanding of entry, immunity and evolution of CoV S proteins.",2017 May 23,"['Ou, Xiuyuan', 'Guan, Hongxin', 'Qin, Bo', 'Mu, Zhixia', 'Wojdyla, Justyna A.', 'Wang, Meitian', 'Dominguez, Samuel R.', 'Qian, Zhaohui', 'Cui, Sheng']",Nat Commun,,,False
fb4cdfdd952f7140a732d294b97f611c456aa6f0,PMC,Vectored immunoprophylaxis: an emerging adjunct to traditional vaccination,http://dx.doi.org/10.1186/s40794-017-0046-0,PMC5531025,28883973,CC BY,"The successful development of effective vaccines has been elusive for many of the world’s most important infectious diseases. Additionally, much of the population, such as the aged or immunocompromised, are unable to mount an effective immunologic response for existing vaccines. Vectored Immunoprophylaxis (VIP) is a novel approach designed to address these challenges. Rather than utilizing an antigen to trigger a response from the host’s immune system as is normally done with traditional vaccines, VIP genetically engineers the production of tailored antibodies from non-hematopoietic cells, bypassing the humoral immune system. Direct administration of genes encoding for neutralizing antibodies has proven to be effective in both preventing and treating several infectious diseases in animal models. While, a significant amount of work has focused on HIV, including an ongoing clinical trial, the approach has also been shown to be effective for malaria, dengue, hepatitis C, influenza, and more. In addition to presenting itself as a potentially efficient approach to solving long-standing vaccine challenges, the approach may be the best, if not only, method to vaccinate immunocompromised individuals. Many issues still need to be addressed, including which tissue(s) makes the most suitable platform, which vector(s) are most efficient at transducing the platform tissue used to secrete the antibodies, and what are the long-term effects of such a treatment. Here we provide a brief overview of this approach, and its potential application in treating some of the world’s most intractable infectious diseases.",2017 Feb 10,"['Sanders, John W.', 'Ponzio, Todd A.']",Trop Dis Travel Med Vaccines,,,True
de836dc0077e520bc97ba60c40fab7a6af4d8224,PMC,Comprehensive structural analysis of designed incomplete polypeptide chains of the replicase nonstructural protein 1 from the severe acute respiratory syndrome coronavirus,http://dx.doi.org/10.1371/journal.pone.0182132,PMC5531528,28750053,CC BY,"The cotranslational folding is recognized as a very cooperative process that occurs after the nearly completion of the polypeptide sequence of a domain. Here we investigated the challenges faced by polypeptide segments of a non-vectorial β-barrel fold. Besides the biological interest behind the SARS coronavirus non-structural protein 1 (nsp1, 117 amino acids), this study model has two structural features that motivated its use in this work: 1- its recombinant production is dependent on the temperature, with greater solubility when expressed at low temperatures. This is an indication of the cotranslational guidance to the native protein conformation. 2- Conversely, nsp1 has a six-stranded, mixed parallel/antiparallel β-barrel with intricate long-range interactions, indicating it will need the full-length protein to fold properly. We used non-denaturing purification conditions that allowed the characterization of polypeptide chains of different lengths, mimicking the landscape of the cotranslational fold of a β-barrel, and avoiding the major technical hindrances of working with the nascent polypeptide bound to the ribosome. Our results showed partially folded states formed as soon as the amino acids of the second β-strand were present (55 amino acids). These partially folded states are different based on the length of polypeptide chain. The native α-helix (amino acids 24–37) was identified as a transient structure (~20–30% propensity). We identified the presence of regular secondary structure after the fourth native β-strand is present (89 amino acids), in parallel to the collapse to a non-native 3D structure. Interestingly the polypeptide sequences of the native strands β2, β3 and β4 have characteristics of α-helices. Our comprehensive analyses support the idea that incomplete polypeptide chains, such as the ones of nascent proteins much earlier than the end of the translation, adopt an abundance of specific transient folds, instead of disordered conformations.",2017 Jul 27,"['Vazquez, Leonardo', 'e Lima, Luis Mauricio Trambaioli da Rocha', 'Almeida, Marcius da Silva']",PLoS One,,,True
bd45834afc3184d92957993038c6889353797fc1,PMC,Zika virus inhibits eIF2α-dependent stress granule assembly,http://dx.doi.org/10.1371/journal.pntd.0005775,PMC5531678,28715409,CC BY,"Zika virus (ZIKV), a member of the Flaviviridae family, is the most recent emerging arbovirus with pandemic potential. During infection, viruses trigger the host cell stress response, leading to changes in RNA translation and the assembly of large aggregates of stalled translation preinitiation complexes, termed stress granules (SGs). Several reports demonstrate that flaviviruses modulate the assembly of stress granules (SG). As an emerging pathogen, little is known however about how ZIKV modulates the host cell stress response. In this work, we investigate how ZIKV modulates SG assembly. We demonstrate that ZIKV negatively impacts SG assembly under oxidative stress conditions induced by sodium arsenite (Ars), a treatment that leads to the phosphorylation of eIF2α. By contrast, no measurable difference in SG assembly was observed between mock and ZIKV-infected cells treated with sodium selenite (Se) or Pateamine A (PatA), compounds that trigger eIF2α-independent SG assembly. Interestingly, ZIKV infection markedly impaired the phosphorylation of eIF2α triggered in Ars-treated infected cells, and the abrogation of SG assembly in ZIKV-infected cells is, at least in part, dependent on eIF2α dephosphorylation. These data demonstrate that ZIKV elicits mechanisms to counteract host anti-viral stress responses to promote a cellular environment propitious for viral replication.",2017 Jul 17,"['Amorim, Raquel', 'Temzi, Abdelkrim', 'Griffin, Bryan D.', 'Mouland, Andrew J.']",PLoS Negl Trop Dis,,,True
07899a6af647ba443bf04599aa35d111d0d08cb3,PMC,Multiple Sclerosis: Immunopathology and Treatment Update,http://dx.doi.org/10.3390/brainsci7070078,PMC5532591,28686222,CC BY,"The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments. We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS.",2017 Jul 7,"['Dargahi, Narges', 'Katsara, Maria', 'Tselios, Theodore', 'Androutsou, Maria-Eleni', 'de Courten, Maximilian', 'Matsoukas, John', 'Apostolopoulos, Vasso']",Brain Sci,,,True
6e0759e9f0c620a14bac6b9939d66bf18847de9c,PMC,Vimentin Modulates Infectious Internalization of Human Papillomavirus 16 Pseudovirions,http://dx.doi.org/10.1128/JVI.00307-17,PMC5533935,28566373,CC BY,"Human papillomavirus (HPV) infection is the most common viral infection of the reproductive tract, with virtually all cases of cervical cancer being attributable to infection by oncogenic HPVs. However, the exact mechanism and receptors used by HPV to infect epithelial cells are controversial. The current entry model suggests that HPV initially attaches to heparan sulfate proteoglycans (HSPGs) at the cell surface, followed by conformational changes, cleavage by furin convertase, and subsequent transfer of the virus to an as-yet-unidentified high-affinity receptor. In line with this model, we established an in vitro infection system using the HSPG-deficient cell line pgsD677 together with HPV16 pseudovirions (HPV16-PsVs). While pgsD677 cells were nonpermissive for untreated HPV16-PsVs, furin cleavage of the particles led to a substantial increase in infection. Biochemical pulldown assays followed by mass spectrometry analysis showed that furin-precleaved HPV16-PsVs specifically interacted with surface-expressed vimentin on pgsD677 cells. We further demonstrated that both furin-precleaved and uncleaved HPV16-PsVs colocalized with surface-expressed vimentin on pgsD677, HeLa, HaCaT, and NIKS cells, while binding of incoming viral particles to soluble vimentin protein before infection led to a substantial decrease in viral uptake. Interestingly, decreasing cell surface vimentin by small interfering RNA (siRNA) knockdown in HeLa and NIKS cells significantly increased HPV16-PsV infectious internalization, while overexpression of vimentin had the opposite effect. The identification of vimentin as an HPV restriction factor enhances our understanding of the initial steps of HPV-host interaction and may lay the basis for the design of novel antiviral drugs preventing HPV internalization into epithelial cells. IMPORTANCE Despite HPV being a highly prevalent sexually transmitted virus causing significant disease burden worldwide, particularly cancer of the cervix, cell surface events preceding oncogenic HPV internalization are poorly understood. We herein describe the identification of surface-expressed vimentin as a novel molecule not previously implicated in the infectious internalization of HPV16. Contrary to our expectations, vimentin was found to act not as a receptor but rather as a restriction factor dampening the initial steps of HPV16 infection. These results importantly contribute to our current understanding of the molecular events during the infectious internalization of HPV16 and open a new direction in the development of alternative drugs to prevent HPV infection.",2017 Jul 27,"['Schäfer, Georgia', 'Graham, Lisa M.', 'Lang, Dirk M.', 'Blumenthal, Melissa J.', 'Bergant Marušič, Martina', 'Katz, Arieh A.']",J Virol,,,True
6f95128d6a8899b5c90dc234a613d4b08415a9e2,PMC,"The process by which perceived autonomy support predicts motivation, intention, and behavior for seasonal influenza prevention in Hong Kong older adults",http://dx.doi.org/10.1186/s12889-017-4608-x,PMC5534058,28754156,CC BY,"BACKGROUND: This study examined the effectiveness of a theoretical framework that integrates self-determination theory (SDT) and the theory of planned behavior (TPB) in explaining the use of facemasks to prevent seasonal influenza among Hong Kong older adults. METHODS: Data were collected at two time points in the winter in Hong Kong, during which influenza is most prevalent. At Time 1, older adults (N = 141) completed self-report measures of SDT (perceived autonomy support from senior center staff, autonomous motivation for influenza prevention) and TPB (attitude, subjective norm, perceived behavioral control, and intention for influenza prevention) constructs with respect to facemask used to prevent infection. Two weeks later, at Time 2, participants’ acceptance of a facemask to prevent influenza in the presence of an experimenter with flu-like symptoms was recorded. RESULTS: Path analysis found that perceived autonomy support of senior center staff was positively and significantly linked to autonomous motivation for facemask use, which, in turn, was positively related to intentions to wear facemasks through the mediation of attitude, subjective norm, and perceived behavioral control. However, the effect of intention on facemask use was not significant. CONCLUSIONS: Results generally support the proposed framework and the findings of previous studies with respect to intention, but the non-significant intention-behavior relationship may warrant future research to examine the reasons for older adults not to wear facemasks to prevent seasonal influenza despite having positive intentions to do so.",2017 Jul 28,"['Chung, Pak-Kwong', 'Zhang, Chun-Qing', 'Liu, Jing-Dong', 'Chan, Derwin King-Chung', 'Si, Gangyan', 'Hagger, Martin S.']",BMC Public Health,,,True
c44ca052440fbba971baea20540e107fc480e836,PMC,Alterations in Gene Expression of Components of the Renin-Angiotensin System and Its Related Enzymes in Lung Cancer,http://dx.doi.org/10.1155/2017/6914976,PMC5534309,28791183,CC BY,"OBJECTIVES: The study assessed the existence and significance of associations between the expression of fifteen renin-angiotensin system component genes and lung adenocarcinoma. MATERIALS AND METHODS: NCBI's built-in statistical tool, GEO2R, was used to calculate Student's t-tests for the associations found in a DNA expression study of adenocarcinoma and matched healthy lung tissue samples. The raw data was processed with GeneSpring™ and then used to generate figures with and without Sidak's multiple comparison correction. RESULTS: Ten genes were found to be significantly associated with adenocarcinoma. Seven of these associations remained statistically significant after correction for multiple comparisons. Notably, AGTR2, which encodes the AT(2) angiotensin II receptor subtype, was significantly underexpressed in adenocarcinoma tissue (p < 0.01). AGTR1, ACE, ENPEP, MME, and PRCP, which encode the AT(1) angiotensin II receptor, angiotensin-converting enzyme, aminopeptidase N, neprilysin, and prolylcarboxypeptidase, respectively, were also underexpressed. AGT, which encodes angiotensinogen, the angiotensin peptide precursor, was overexpressed in adenocarcinoma tissue. CONCLUSION: The results suggest an association between the expression of the genes for renin-angiotensin system-related proteins and adenocarcinoma. While further research is necessary to conclusively demonstrate a link between the renin-angiotensin system and lung cancers, the results suggest that the renin-angiotensin system plays a role in the pathology of adenocarcinoma.",2017 Jul 16,"['Goldstein, Benjamin', 'Trivedi, Malav', 'Speth, Robert C.']",Lung Cancer Int,,,True
ab5bba6cb4c6f9a00931f232ac3be14667c4f807,PMC,Characterisation of the Chemical Composition and Structural Features of Novel Antimicrobial Nanoparticles,http://dx.doi.org/10.3390/nano7070152,PMC5535218,28644384,CC BY,"Three antimicrobial nanoparticle types (AMNP0, AMNP1, and AMNP2) produced using the Tesima(TM) thermal plasma technology were investigated and their compositions were determined using a combination of analytical methods. Scanning electron micrographs provided the morphology of these particles with observed sizes ranging from 10 to 50 nm, whilst FTIR spectra confirmed the absence of polar bonds and organic impurities, and strong Raman active vibrational bands at ca. 1604 and 1311 cm(−1) ascribed to C–C vibrational motions were observed. Carbon signals that resonated at δ(C) 126 ppm in the solid state NMR spectra confirmed that sp(2) hybridised carbons were present in high concentration in two of the nanoparticle types (AMNP1 and AMNP2). X-ray powder diffraction suggested that AMNP0 contains single phase Tungsten carbide (WC) in a high state of purity and multiple phases of WC/WC(1-x) were identified in both AMNP1 and AMNP2. Finally, X-ray photoelectron spectral (XPS) analyses revealed and quantified the elemental ratios in these composite formulations.",2017 Jun 23,"['Cheong, Yuen-Ki', 'Calvo-Castro, Jesus', 'Ciric, Lena', 'Edirisinghe, Mohan', 'Cloutman-Green, Elaine', 'Illangakoon, Upulitha Eranka', 'Kang, Qiang', 'Mahalingam, Suntharavathanan', 'Matharu, Rupy Kaur', 'Wilson, Rory M.', 'Ren, Guogang']",Nanomaterials (Basel),,,True
e20efa446b9d31196d08c2a0cf51d2c851bfbbad,PMC,Beyond pilotitis: taking digital health interventions to the national level in China and Uganda,http://dx.doi.org/10.1186/s12992-017-0275-z,PMC5535287,28756767,CC BY,"BACKGROUND: Innovation theory has focused on the adoption of new products or services by individuals and their market-driven diffusion to the population at large. However, major health sector innovations typically emerge from negotiations between diverse stakeholders who compete to impose or at least prioritise their preferred version of that innovation. Thus, while many digital health interventions have succeeded in terms of adoption by a substantial number of providers and patients, they have generally failed to gain the level of acceptance required for their integration into national health systems that would promote sustainability and population-wide application. The area of innovation considered here relates to a growing number of success stories that have created considerable enthusiasm among donors, international agencies, and governments for the potential role of ICTs in transforming weak national health information systems in middle and low income countries. This article uses a case study approach to consider the assumptions, institutional as well as technical, underlying this enthusiasm and explores possible ways in which outcomes might be improved. METHODS: Literature review and case study analysis. RESULTS: The two systems considered have had considerable success in terms of gaining and maintaining government support and addressing the concerns of providers without compromising their core elements. In Uganda, the system has flourished in spite of severe resource constraints, using a participatory approach that has encouraged a high level of community engagement. In China, concern with past failures generated the political will to build a high quality surveillance system, using the latest technology and drawing on a highly skilled human resource base. CONCLUSIONS: Both example stress the importance of recognising the political, social and historical context within which information systems have to function. Implementers need to focus as much on the perceptions, attitudes and needs of stakeholders as on the technology. Implementers should distinguish between factors which may influence engagement at an institutional level and those aimed at supporting and supervising individuals within those institutions. Finally, we would suggest that designing interoperability into systems at the outset, rather than assuming that this can be achieved at some point in the future, may prove far easier in the longer term.",2017 Jul 31,"['Huang, Fei', 'Blaschke, Sean', 'Lucas, Henry']",Global Health,,,True
2ee77e390b7b181cef6dfca17f4a6aeab09d0064,PMC,Mechanistic Insight into Long Noncoding RNAs and the Placenta,http://dx.doi.org/10.3390/ijms18071371,PMC5535864,28653993,CC BY,"Long non-coding RNAs (lncRNAs) are classified as RNAs greater than 200 nucleotides in length that do not produce a protein product. lncRNAs are expressed with cellular and temporal specificity and have been shown to play a role in many cellular events, including the regulation of gene expression, post-transcriptional modifications and epigenetic modifications. Since lncRNAs were first discovered, there has been increasing evidence that they play important roles in the development and function of most organs, including the placenta. The placenta is an essential transient organ that facilitates communication and nutrient exchange between the mother and foetus. The placenta is of foetal origin and begins to form shortly after the embryo implants into the uterine wall. The placenta relies heavily on the successful differentiation and function of trophoblast cells, including invasion as well as the formation of the maternal/foetal interface. Here, we review the current literature surrounding the involvement of lncRNAs in the development and function of trophoblasts and the human placenta.",2017 Jun 27,"['McAninch, Dale', 'Roberts, Claire T.', 'Bianco-Miotto, Tina']",Int J Mol Sci,,,True
2ba9b89e1cab4bfe6b3b82046e458fec8eb12bbd,PMC,cAMP-dependent activation of protein kinase A attenuates respiratory syncytial virus-induced human airway epithelial barrier disruption,http://dx.doi.org/10.1371/journal.pone.0181876,PMC5536269,28759570,CC BY,"Airway epithelium forms a barrier to the outside world and has a crucial role in susceptibility to viral infections. Cyclic adenosine monophosphate (cAMP) is an important second messenger acting via two intracellular signaling molecules: protein kinase A (PKA) and the guanidine nucleotide exchange factor, Epac. We sought to investigate effects of increased cAMP level on the disruption of model airway epithelial barrier caused by RSV infection and the molecular mechanisms underlying cAMP actions. Human bronchial epithelial cells were infected with RSV-A2 and treated with either cAMP releasing agent, forskolin, or cAMP analogs. Structure and functions of the Apical Junctional Complex (AJC) were evaluated by measuring transepithelial electrical resistance and permeability to FITC-dextran, and determining localization of AJC proteins by confocal microscopy. Increased intracellular cAMP level significantly attenuated RSV-induced disassembly of AJC. These barrier-protective effects of cAMP were due to the activation of PKA signaling and did not involve Epac activity. Increased cAMP level reduced RSV-induced reorganization of the actin cytoskeleton, including apical accumulation of an essential actin-binding protein, cortactin, and inhibited expression of the RSV F protein. These barrier-protective and antiviral-function of cAMP signaling were evident even when cAMP level was increased after the onset of RSV infection. Taken together, our study demonstrates that cAMP/PKA signaling attenuated RSV-induced disruption of structure and functions of the model airway epithelial barrier by mechanisms involving the stabilization of epithelial junctions and inhibition of viral biogenesis. Improving our understanding of the mechanisms involved in RSV-induced epithelial dysfunction and viral pathogenesis will help to develop novel anti-viral therapeutic approaches.",2017 Jul 31,"['Rezaee, Fariba', 'Harford, Terri J.', 'Linfield, Debra T.', 'Altawallbeh, Ghaith', 'Midura, Ronald J.', 'Ivanov, Andrei I.', 'Piedimonte, Giovanni']",PLoS One,,,True
39fae6df128e98e970b22ea35cebdaaac78a647e,PMC,Spatial modelling of contribution of individual level risk factors for mortality from Middle East respiratory syndrome coronavirus in the Arabian Peninsula,http://dx.doi.org/10.1371/journal.pone.0181215,PMC5536289,28759623,CC BY,"BACKGROUND: Middle East respiratory syndrome coronavirus is a contagious respiratory pathogen that is contracted via close contact with an infected subject. Transmission of the pathogen has occurred through animal-to-human contact at first followed by human-to-human contact within families and health care facilities. DATA AND METHODS: This study is based on a retrospective analysis of the Middle East respiratory syndrome coronavirus outbreak in the Kingdom of Saudi Arabia between June 2012 and July 2015. A Geoadditive variable model for binary outcomes was applied to account for both individual level risk factors as well spatial variation via a fully Bayesian approach. RESULTS: Out of 959 confirmed cases, 642 (67%) were males and 317 (33%) had died. Three hundred and sixty four (38%) cases occurred in Ar Riyad province, while 325 (34%) cases occurred in Makkah. Individuals with some comorbidity had a significantly higher likelihood of dying from MERS-CoV compared with those who did not suffer comorbidity [Odds ratio (OR) = 2.071; 95% confidence interval (CI): 1.307, 3.263]. Health-care workers were significantly less likely to die from the disease compared with non-health workers [OR = 0.372, 95% CI: 0.151, 0.827]. Patients who had fatal clinical experience and those with clinical and subclinical experiences were equally less likely to die from the disease compared with patients who did not have fatal clinical experience and those without clinical and subclinical experiences respectively. The odds of dying from the disease was found to increase as age increased beyond 25 years and was much higher for individuals with any underlying comorbidities. CONCLUSION: Interventions to minimize mortality from the Middle East respiratory syndrome coronavirus should particularly focus individuals with comorbidity, non-health-care workers, patients with no clinical fatal experience, and patients without any clinical and subclinical experiences.",2017 Jul 31,"['Adegboye, Oyelola A.', 'Gayawan, Ezra', 'Hanna, Fahad']",PLoS One,,,True
931813f78c97a77e36fb83d93728cffc0106d427,PMC,Telerehabilitation Solution Conceptual Paper for Community-Based Exercise Rehabilitation of Patients Discharged After Critical Illness,http://dx.doi.org/10.5195/ijt.2016.6205,PMC5536730,28775802,CC BY,"A novel service oriented platform has been developed under the framework of the Telerehabilitation Service funded by the Cross Border Cooperation Programme Greece Cyprus 2007 – 2013 to support tele-supervised exercise rehabilitation for patients after hospitalization in intensive care units (ICU). The platform enables multiparty, interregional bidirectional audio/visual communication between clinical practitioners and post-ICU patients. It also enables patient group-based vital sign real time monitoring, patients’ clinical record bookkeeping, and individualized and group-based patient online exercise programs. The exercise programs intended for the service are based on successful cardiorespiratory rehabilitation programs, individualized and monitored by a multidisciplinary team. The eligibility study of former ICU patients to participate in such a service as well as a cost benefit analysis are presented to support the cost effectiveness of the telerehabilitation program in addition to the expected health benefits to a large proportion of former ICU patients.",2016 Dec 15,"['TSAVOURELOU, APHRODITE', 'STYLIANIDES, NIKOLAS', 'PAPADOPOULOS, ANDREAS', 'DIKAIAKOS, MARIOS D.', 'NANAS, SERAFEIM', 'KYPRIANOY, THEODOROS', 'TOKMAKIDIS, SAVVAS P.']",Int J Telerehabil,,,True
38cbb822fbce17d5cbd5d12896d8ffa7848e8229,PMC,A peptide-based viral inactivator inhibits Zika virus infection in pregnant mice and fetuses,http://dx.doi.org/10.1038/ncomms15672,PMC5537589,28742068,CC BY,"Zika virus (ZIKV), a re-emerging flavivirus associated with neurological disorders, has spread rapidly to more than 70 countries and territories. However, no specific vaccines or antiviral drugs are currently available to prevent or treat ZIKV infection. Here we report that a synthetic peptide derived from the stem region of ZIKV envelope protein, designated Z2, potently inhibits infection of ZIKV and other flaviviruses in vitro. We show that Z2 interacts with ZIKV surface protein and disrupts the integrity of the viral membrane. Z2 can penetrate the placental barrier to enter fetal tissues and is safe for use in pregnant mice. Intraperitoneal administration of Z2 inhibits vertical transmission of ZIKV in pregnant C57BL/6 mice and protects type I or type I/II interferon receptor-deficient mice against lethal ZIKV challenge. Thus, Z2 has potential to be further developed as an antiviral treatment against ZIKV infection in high-risk populations, particularly pregnant women.",2017 Jul 25,"['Yu, Yufeng', 'Deng, Yong-Qiang', 'Zou, Peng', 'Wang, Qian', 'Dai, Yanyan', 'Yu, Fei', 'Du, Lanying', 'Zhang, Na-Na', 'Tian, Min', 'Hao, Jia-Nan', 'Meng, Yu', 'Li, Yuan', 'Zhou, Xiaohui', 'Fuk-Woo Chan, Jasper', 'Yuen, Kwok-Yung', 'Qin, Cheng-Feng', 'Jiang, Shibo', 'Lu, Lu']",Nat Commun,,,True
9a90801f32edf2910a4cb873d9db0181808171bb,PMC,A peptide-based viral inactivator inhibits Zika virus infection in pregnant mice and fetuses,http://dx.doi.org/10.1038/ncomms15672,PMC5537589,28742068,CC BY,"Zika virus (ZIKV), a re-emerging flavivirus associated with neurological disorders, has spread rapidly to more than 70 countries and territories. However, no specific vaccines or antiviral drugs are currently available to prevent or treat ZIKV infection. Here we report that a synthetic peptide derived from the stem region of ZIKV envelope protein, designated Z2, potently inhibits infection of ZIKV and other flaviviruses in vitro. We show that Z2 interacts with ZIKV surface protein and disrupts the integrity of the viral membrane. Z2 can penetrate the placental barrier to enter fetal tissues and is safe for use in pregnant mice. Intraperitoneal administration of Z2 inhibits vertical transmission of ZIKV in pregnant C57BL/6 mice and protects type I or type I/II interferon receptor-deficient mice against lethal ZIKV challenge. Thus, Z2 has potential to be further developed as an antiviral treatment against ZIKV infection in high-risk populations, particularly pregnant women.",2017 Jul 25,"['Yu, Yufeng', 'Deng, Yong-Qiang', 'Zou, Peng', 'Wang, Qian', 'Dai, Yanyan', 'Yu, Fei', 'Du, Lanying', 'Zhang, Na-Na', 'Tian, Min', 'Hao, Jia-Nan', 'Meng, Yu', 'Li, Yuan', 'Zhou, Xiaohui', 'Fuk-Woo Chan, Jasper', 'Yuen, Kwok-Yung', 'Qin, Cheng-Feng', 'Jiang, Shibo', 'Lu, Lu']",Nat Commun,,,False
f582baa8aa4a5f3af8356e86df3d5c29ff426c85,PMC,A peptide-based viral inactivator inhibits Zika virus infection in pregnant mice and fetuses,http://dx.doi.org/10.1038/ncomms15672,PMC5537589,28742068,CC BY,"Zika virus (ZIKV), a re-emerging flavivirus associated with neurological disorders, has spread rapidly to more than 70 countries and territories. However, no specific vaccines or antiviral drugs are currently available to prevent or treat ZIKV infection. Here we report that a synthetic peptide derived from the stem region of ZIKV envelope protein, designated Z2, potently inhibits infection of ZIKV and other flaviviruses in vitro. We show that Z2 interacts with ZIKV surface protein and disrupts the integrity of the viral membrane. Z2 can penetrate the placental barrier to enter fetal tissues and is safe for use in pregnant mice. Intraperitoneal administration of Z2 inhibits vertical transmission of ZIKV in pregnant C57BL/6 mice and protects type I or type I/II interferon receptor-deficient mice against lethal ZIKV challenge. Thus, Z2 has potential to be further developed as an antiviral treatment against ZIKV infection in high-risk populations, particularly pregnant women.",2017 Jul 25,"['Yu, Yufeng', 'Deng, Yong-Qiang', 'Zou, Peng', 'Wang, Qian', 'Dai, Yanyan', 'Yu, Fei', 'Du, Lanying', 'Zhang, Na-Na', 'Tian, Min', 'Hao, Jia-Nan', 'Meng, Yu', 'Li, Yuan', 'Zhou, Xiaohui', 'Fuk-Woo Chan, Jasper', 'Yuen, Kwok-Yung', 'Qin, Cheng-Feng', 'Jiang, Shibo', 'Lu, Lu']",Nat Commun,,,True
6d480c492ee63a4f78a6f6aa78260d79d3e281bc,PMC,"Effective Suckling C57BL/6, Kunming, and BALB/c Mouse Models with Remarkable Neurological Manifestation for Zika Virus Infection",http://dx.doi.org/10.3390/v9070165,PMC5537657,28661429,CC BY,"Since 2015, 84 countries and territories reported evidence of vector-borne Zika Virus (ZIKV) transmission. The World Health Organization (WHO) declared that ZIKV and associated consequences especially the neurological autoimmune disorder Guillain–Barré syndrome (GBS) and microcephaly will remain a significant enduring public health challenge requiring intense action. We apply a standardization of the multi-subcutaneous dorsal inoculation method to systematically summarize clinical neurological manifestation, viral distribution, and tissue damage during the progress of viremia and systemic spread in suckling mouse models. We found that C57BL/6 and Kunming mice (KM) both showed remarkable and uniform neurologic manifestations. C57BL/6 owned the highest susceptibility and pathogenicity to the nervous system, referred to as movement disorders, with 100% incidence, while KM was an economic model for a Chinese study characterized by lower limb weakness with 62% morbidity. Slight yellow extraocular exudates were observed in BALB/c, suggesting the association with similar ocular findings to those of clinical cases. The virus distribution and pathological changes in the sera, brains, livers, kidneys, spleens, and testes during disease progression had strong regularity and uniformity, demonstrating the effectiveness and plasticity of the animal models. The successful establishment of these animal models will be conducive to expound the pathogenic mechanism of GBS.",2017 Jun 29,"['Yu, Jianhai', 'Liu, Xuling', 'Ke, Changwen', 'Wu, Qinghua', 'Lu, Weizhi', 'Qin, Zhiran', 'He, Xiaoen', 'Liu, Yujing', 'Deng, Jieli', 'Xu, Suiqi', 'Li, Ying', 'Zhu, Li', 'Wan, Chengsong', 'Zhang, Qiwei', 'Xiao, Weiwei', 'Xie, Qian', 'Zhang, Bao', 'Zhao, Wei']",Viruses,,,True
cac120abb934d9ce2974326a0f98eef4ec6dd07e,PMC,Porcine Epidemic Diarrhea in Europe: In-Detail Analyses of Disease Dynamics and Molecular Epidemiology,http://dx.doi.org/10.3390/v9070177,PMC5537669,28684708,CC BY,"Porcine epidemic diarrhea (PED) is an acute and highly contagious enteric disease of swine caused by the eponymous virus (PEDV) which belongs to the genus Alphacoronavirus within the Coronaviridae virus family. Following the disastrous outbreaks in Asia and the United States, PEDV has been detected also in Europe. In order to better understand the overall situation, the molecular epidemiology, and factors that might influence the most variable disease impact; 40 samples from swine feces were collected from different PED outbreaks in Germany and other European countries and sequenced by shot-gun next-generation sequencing. A total of 38 new PEDV complete coding sequences were generated. When compared on a global scale, all investigated sequences from Central and South-Eastern Europe formed a rather homogeneous PEDV S INDEL cluster, suggesting a recent re-introduction. However, in-detail analyses revealed two new clusters and putative ancestor strains. Based on the available background data, correlations between clusters and location, farm type or clinical presentation could not be established. Additionally, the impact of secondary infections was explored using the metagenomic data sets. While several coinfections were observed, no correlation was found with disease courses. However, in addition to the PEDV genomes, ten complete viral coding sequences from nine different data sets were reconstructed each representing new virus strains. In detail, three pasivirus A strains, two astroviruses, a porcine sapelovirus, a kobuvirus, a porcine torovirus, a posavirus, and an enterobacteria phage were almost fully sequenced.",2017 Jul 6,"['Hanke, Dennis', 'Pohlmann, Anne', 'Sauter-Louis, Carola', 'Höper, Dirk', 'Stadler, Julia', 'Ritzmann, Mathias', 'Steinrigl, Adi', 'Schwarz, Bernd-Andreas', 'Akimkin, Valerij', 'Fux, Robert', 'Blome, Sandra', 'Beer, Martin']",Viruses,,,True
90ef0ef31217f9768282d8cd00ce3a7865ba0ed1,PMC,Porcine Epidemic Diarrhea in Europe: In-Detail Analyses of Disease Dynamics and Molecular Epidemiology,http://dx.doi.org/10.3390/v9070177,PMC5537669,28684708,CC BY,"Porcine epidemic diarrhea (PED) is an acute and highly contagious enteric disease of swine caused by the eponymous virus (PEDV) which belongs to the genus Alphacoronavirus within the Coronaviridae virus family. Following the disastrous outbreaks in Asia and the United States, PEDV has been detected also in Europe. In order to better understand the overall situation, the molecular epidemiology, and factors that might influence the most variable disease impact; 40 samples from swine feces were collected from different PED outbreaks in Germany and other European countries and sequenced by shot-gun next-generation sequencing. A total of 38 new PEDV complete coding sequences were generated. When compared on a global scale, all investigated sequences from Central and South-Eastern Europe formed a rather homogeneous PEDV S INDEL cluster, suggesting a recent re-introduction. However, in-detail analyses revealed two new clusters and putative ancestor strains. Based on the available background data, correlations between clusters and location, farm type or clinical presentation could not be established. Additionally, the impact of secondary infections was explored using the metagenomic data sets. While several coinfections were observed, no correlation was found with disease courses. However, in addition to the PEDV genomes, ten complete viral coding sequences from nine different data sets were reconstructed each representing new virus strains. In detail, three pasivirus A strains, two astroviruses, a porcine sapelovirus, a kobuvirus, a porcine torovirus, a posavirus, and an enterobacteria phage were almost fully sequenced.",2017 Jul 6,"['Hanke, Dennis', 'Pohlmann, Anne', 'Sauter-Louis, Carola', 'Höper, Dirk', 'Stadler, Julia', 'Ritzmann, Mathias', 'Steinrigl, Adi', 'Schwarz, Bernd-Andreas', 'Akimkin, Valerij', 'Fux, Robert', 'Blome, Sandra', 'Beer, Martin']",Viruses,,,False
0d82c429737f250a7bcd230fea2e4725edc2439a,PMC,The Interaction between Nidovirales and Autophagy Components,http://dx.doi.org/10.3390/v9070182,PMC5537674,28696396,CC BY,"Autophagy is a conserved intracellular catabolic pathway that allows cells to maintain homeostasis through the degradation of deleterious components via specialized double-membrane vesicles called autophagosomes. During the past decades, it has been revealed that numerous pathogens, including viruses, usurp autophagy in order to promote their propagation. Nidovirales are an order of enveloped viruses with large single-stranded positive RNA genomes. Four virus families (Arterividae, Coronaviridae, Mesoniviridae, and Roniviridae) are part of this order, which comprises several human and animal pathogens of medical and veterinary importance. In host cells, Nidovirales induce membrane rearrangements including autophagosome formation. The relevance and putative mechanism of autophagy usurpation, however, remain largely elusive. Here, we review the current knowledge about the possible interplay between Nidovirales and autophagy.",2017 Jul 11,"['Cong, Yingying', 'Verlhac, Pauline', 'Reggiori, Fulvio']",Viruses,,,True
5ae9d09818e63828c80da0e37f6a5c1a1ccc22e6,PMC,Developing international open science collaborations: Funder reflections on the Open Science Prize,http://dx.doi.org/10.1371/journal.pbio.2002617,PMC5538631,28763440,CC0,"The Open Science Prize was established with the following objectives: first, to encourage the crowdsourcing of open data to make breakthroughs that are of biomedical significance; second, to illustrate that funders can indeed work together when scientific interests are aligned; and finally, to encourage international collaboration between investigators with the intent of achieving important innovations that would not be possible otherwise. The process for running the competition and the successes and challenges that arose are presented.",2017 Aug 1,"['Kittrie, Elizabeth', 'Atienza, Audie A.', 'Kiley, Robert', 'Carr, David', 'MacFarlane, Aki', 'Pai, Vinay', 'Couch, Jennifer', 'Bajkowski, Jared', 'Bonner, Joseph F.', 'Mietchen, Daniel', 'Bourne, Philip E.']",PLoS Biol,,,True
ef485cbb4af39866ed7fdb5ec0ce66f92e39511f,PMC,Infectious bronchitis corona virus establishes productive infection in avian macrophages interfering with selected antimicrobial functions,http://dx.doi.org/10.1371/journal.pone.0181801,PMC5538654,28763472,CC BY,"Infectious bronchitis virus (IBV) causes respiratory disease leading to loss of egg and meat production in chickens. Although it is known that macrophage numbers are elevated in the respiratory tract of IBV infected chickens, the role played by macrophages in IBV infection, particularly as a target cell for viral replication, is unknown. In this study, first, we investigated the ability of IBV to establish productive replication in macrophages in lungs and trachea in vivo and in macrophage cell cultures in vitro using two pathogenic IBV strains. Using a double immunofluorescent technique, we observed that both IBV Massachusetts-type 41 (M41) and Connecticut A5968 (Conn A5968) strains replicate in avian macrophages at a low level in vivo. This in vivo observation was substantiated by demonstrating IBV antigens in macrophages following in vitro IBV infection. Further, IBV productive infection in macrophages was confirmed by demonstrating corona viral particles in macrophages and IBV ribonucleic acid (RNA) in culture supernatants. Evaluation of the functions of macrophages following infection of macrophages with IBV M41 and Conn A5968 strains revealed that the production of antimicrobial molecule, nitric oxide (NO) is inhibited. It was also noted that replication of IBV M41 and Conn A5968 strains in macrophages does not interfere with the induction of type 1 IFN activity by macrophages. In conclusion, both M41 and Con A5968 IBV strains infect macrophages in vivo and in vitro resulting productive replications. During the replication of IBV in macrophages, their ability to produce NO can be affected without affecting the ability to induce type 1 IFN activity. Further studies are warranted to uncover the significance of macrophage infection of IBV in the pathogenesis of IBV infection in chickens.",2017 Aug 1,"['Amarasinghe, Aruna', 'Abdul-Cader, Mohamed Sarjoon', 'Nazir, Sadiya', 'De Silva Senapathi, Upasama', 'van der Meer, Frank', 'Cork, Susan Catherine', 'Gomis, Susantha', 'Abdul-Careem, Mohamed Faizal']",PLoS One,,,True
95e49a7f605a5fe31fccd9e995785b7b62f4cda8,PMC,Selection of reference genes for expression analysis using RT-qPCR in the dissemination system of Heliothis virescens ascovirus 3 h (HvAV-3h),http://dx.doi.org/10.1038/s41598-017-07684-w,PMC5539149,28765578,CC BY,"Ascoviruses are double-stranded DNA viruses that mainly infect noctuid larvae, and are transmitted by the parasitoid wasp Microplitis similis Lyle. Ascovirus-parasitoids wasp-noctuid insects constitute the dissemination system. Selection of suitable reference genes for the dissemination system could play an important role in elucidating the pathogenic molecular mechanisms of ascovirus. Unfortunately, such studies on potential reference genes in the dissemination system of ascoviruses are lacking. In the present study, we evaluated 11 candidate reference genes: β-actin1 (ACT1), β-actin2 (ACT2), elongation factor 1 (EF1), elongation factor 2 (EF2), ribosomal protein L10 (L10), ribosomal protein L17A (L17A), superoxide dismutase (SOD), 28S ribosome (28S), Tubulin (TUB) and 18S ribosome (18S). The samples were originally from various virus concentrations and points-in-time of experimental treatments using RefFinder and four algorithms. The results showed that EF1 was the most stable internal gene in S. exigua and M. similis and that EF2 was the most stable in the IOZCAS-Spex-II-A cell line, and the stability of reference genes were confirmed via the expression levels of two inhibitor of apoptosis-like (iap-like) genes from Heliothis virescens ascovirus 3 h (HvAV-3h). This study provides a crucial basis for future research that explores the molecular mechanisms of the pathogenesis of ascoviruses.",2017 Aug 1,"['Chen, Zi-Shu', 'Han, Ning-Ning', 'Li, Jian-Hong', 'Huang, Guo-Hua', 'Wan, Hu']",Sci Rep,,,False
e8be80485fdee7344e970941c62ca23fb3eed4da,PMC,Selection of reference genes for expression analysis using RT-qPCR in the dissemination system of Heliothis virescens ascovirus 3 h (HvAV-3h),http://dx.doi.org/10.1038/s41598-017-07684-w,PMC5539149,28765578,CC BY,"Ascoviruses are double-stranded DNA viruses that mainly infect noctuid larvae, and are transmitted by the parasitoid wasp Microplitis similis Lyle. Ascovirus-parasitoids wasp-noctuid insects constitute the dissemination system. Selection of suitable reference genes for the dissemination system could play an important role in elucidating the pathogenic molecular mechanisms of ascovirus. Unfortunately, such studies on potential reference genes in the dissemination system of ascoviruses are lacking. In the present study, we evaluated 11 candidate reference genes: β-actin1 (ACT1), β-actin2 (ACT2), elongation factor 1 (EF1), elongation factor 2 (EF2), ribosomal protein L10 (L10), ribosomal protein L17A (L17A), superoxide dismutase (SOD), 28S ribosome (28S), Tubulin (TUB) and 18S ribosome (18S). The samples were originally from various virus concentrations and points-in-time of experimental treatments using RefFinder and four algorithms. The results showed that EF1 was the most stable internal gene in S. exigua and M. similis and that EF2 was the most stable in the IOZCAS-Spex-II-A cell line, and the stability of reference genes were confirmed via the expression levels of two inhibitor of apoptosis-like (iap-like) genes from Heliothis virescens ascovirus 3 h (HvAV-3h). This study provides a crucial basis for future research that explores the molecular mechanisms of the pathogenesis of ascoviruses.",2017 Aug 1,"['Chen, Zi-Shu', 'Han, Ning-Ning', 'Li, Jian-Hong', 'Huang, Guo-Hua', 'Wan, Hu']",Sci Rep,,,True
e5a095a5f5a45d1476a2c4ec8a2ebb9689112dcb,PMC,Label-free luminescence switch-on detection of hepatitis C virus NS3 helicase activity using a G-quadruplex-selective probe,http://dx.doi.org/10.1039/c4sc03319a,PMC5539802,28808523,CC BY,"A series of luminescent Ir(iii) complexes were synthesised and evaluated for their ability to act as luminescent G-quadruplex-selective probes. The Ir(iii) complex 9, [Ir(phq)(2)(phen)]PF(6) (where phq = 2-phenylquinoline; phen = 1,10-phenanthroline), exhibited high luminescence in the presence of G-quadruplex DNA compared to dsDNA and ssDNA, and was employed to construct a label-free G-quadruplex-based assay for hepatitis C virus NS3 helicase activity in aqueous solution. Moreover, the application of the assay for screening potential helicase inhibitors was demonstrated. To our knowledge, this is the first G-quadruplex-based assay for helicase activity.",2015 Apr 1,"['Leung, Ka-Ho', 'He, Hong-Zhang', 'He, Bingyong', 'Zhong, Hai-Jing', 'Lin, Sheng', 'Wang, Yi-Tao', 'Ma, Dik-Lung', 'Leung, Chung-Hang']",Chem Sci,,,False
aa88be07a840711832d14d1ad8873eea2a219c13,PMC,Label-free luminescence switch-on detection of hepatitis C virus NS3 helicase activity using a G-quadruplex-selective probe,http://dx.doi.org/10.1039/c4sc03319a,PMC5539802,28808523,CC BY,"A series of luminescent Ir(iii) complexes were synthesised and evaluated for their ability to act as luminescent G-quadruplex-selective probes. The Ir(iii) complex 9, [Ir(phq)(2)(phen)]PF(6) (where phq = 2-phenylquinoline; phen = 1,10-phenanthroline), exhibited high luminescence in the presence of G-quadruplex DNA compared to dsDNA and ssDNA, and was employed to construct a label-free G-quadruplex-based assay for hepatitis C virus NS3 helicase activity in aqueous solution. Moreover, the application of the assay for screening potential helicase inhibitors was demonstrated. To our knowledge, this is the first G-quadruplex-based assay for helicase activity.",2015 Apr 1,"['Leung, Ka-Ho', 'He, Hong-Zhang', 'He, Bingyong', 'Zhong, Hai-Jing', 'Lin, Sheng', 'Wang, Yi-Tao', 'Ma, Dik-Lung', 'Leung, Chung-Hang']",Chem Sci,,,False
aa89136217edb205585668227efb1b0a976be854,PMC,An assessment on the role of endophytic microbes in the therapeutic potential of Fagonia indica,http://dx.doi.org/10.1186/s12941-017-0228-7,PMC5540543,28764775,CC BY,"BACKGROUND: Natural products of animals, plants and microbes are potential source of important chemical compounds, with diverse applications including therapeutics. Endophytic bacteria that are especially associated with medicinal plants presents a reservoir of therapeutic compounds. Fagonia indica has been recently investigated by numerous researchers because of its striking therapeutic potential especially in cancer. It is also reported that endophytes play a vital role in the biosynthesis of various metabolites; therefore we believe that endophytes associated with F. indica are of crucial importance in this regard. The present study aims successful isolation, molecular identification of endophytic bacteria and their screening for bioactive metabolites quantification and in vitro pharmacological activities. METHODS: 16S rRNA gene sequencing was used for the identification of isolated endophytic bacteria. Methanolic extracts were evaluated for total phenolic contents (TPC), total flavonoids contents (TFC), DPPH free radical scavenging activity, reducing power and total anti-oxidant assays were performed. And also screened for antibacterial and antifungal activities by disc diffusion method and their MIC were calculated by broth dilution method using microplate reader. Further, standard protocols were followed for antileishmanial activity and protein kinase inhibition. Analysis and statistics were performed using SPSS, Table curve and Origin 8.5 for graphs. RESULTS: Bacterial strains belonging to various genera (Bacillus, Enterobacter, Pantoea, Erwinia and Stenotrophomonas) were isolated and identified. Total phenolic contents and total flavonoids contents varies among all the bacterial extracts respectively in which Bacillus subtilis showed high phenolic contents 243 µg/mg of gallic acid equivalents (GAE) and Stenotrophomonas maltophilia showed high flavonoids contents 15.9 µg/mg quercitin equivalents (QA), total antioxidant capacity (TAC) 37.6 µg/mg of extract, reducing power (RP) 206 µg/mg of extract and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity with 98.7 μg/mL IC(50) value. Although all the extracts tested were active to inhibit growth of selected pathogenic microbes (bacteria and fungi), but significant antibacterial activity was observed against Klebsiella pneumonia and B. subtilis. An Enterobacter cloaca was active against Leishmania tropica with IC(50) value of 1.4 µg/mg extracts. B. subtilis and Bacillus tequilensis correspondingly exhibit significant protein kinase inhibition of 47 ± 0.72 and 42 ± 1.21 mm bald zones, indicating anti-infective and antitumor potential. CONCLUSIONS: Our findings revealed that crude extracts of selected endophytic bacteria from F. indica possess excellent biological activities indicating their potential as an important source of antibiotics (antifungal, antibacterial) compounds.",2017 Aug 1,"['Rahman, Lubna', 'Shinwari, Zabta K.', 'Iqrar, Irum', 'Rahman, Lutfur', 'Tanveer, Faouzia']",Ann Clin Microbiol Antimicrob,,,True
2ff4902f8704407bd2f72325ee5ea75908919a54,PMC,Advances in Developing Therapies to Combat Zika Virus: Current Knowledge and Future Perspectives,http://dx.doi.org/10.3389/fmicb.2017.01469,PMC5541032,28824594,CC BY,"Zika virus (ZIKV) remained largely quiescent for nearly six decades after its first appearance in 1947. ZIKV reappeared after 2007, resulting in a declaration of an international “public health emergency” in 2016 by the World Health Organization (WHO). Until this time, ZIKV was considered to induce only mild illness, but it has now been established as the cause of severe clinical manifestations, including fetal anomalies, neurological problems, and autoimmune disorders. Infection during pregnancy can cause congenital brain abnormalities, including microcephaly and neurological degeneration, and in other cases, Guillain-Barré syndrome, making infections with ZIKV a substantial public health concern. Genomic and molecular investigations are underway to investigate ZIKV pathology and its recent enhanced pathogenicity, as well as to design safe and potent vaccines, drugs, and therapeutics. This review describes progress in the design and development of various anti-ZIKV therapeutics, including drugs targeting virus entry into cells and the helicase protein, nucleosides, inhibitors of NS3 protein, small molecules, methyltransferase inhibitors, interferons, repurposed drugs, drugs designed with the aid of computers, neutralizing antibodies, convalescent serum, antibodies that limit antibody-dependent enhancement, and herbal medicines. Additionally, covalent inhibitors of viral protein expression and anti-Toll-like receptor molecules are discussed. To counter ZIKV-associated disease, we need to make rapid progress in developing novel therapies that work effectually to inhibit ZIKV.",2017 Aug 3,"['Munjal, Ashok', 'Khandia, Rekha', 'Dhama, Kuldeep', 'Sachan, Swati', 'Karthik, Kumaragurubaran', 'Tiwari, Ruchi', 'Malik, Yashpal S.', 'Kumar, Deepak', 'Singh, Raj K.', 'Iqbal, Hafiz M. N.', 'Joshi, Sunil K.']",Front Microbiol,,,True
d5a4d0cd6846bf609769f3274a5cbf22b11b14a5,PMC,Eupatorium fortunei and Its Components Increase Antiviral Immune Responses against RNA Viruses,http://dx.doi.org/10.3389/fphar.2017.00511,PMC5541272,28824435,CC BY,"Eupatorium fortunei (EF) has long been used as herbal medicine in Korea, China, and Asian countries to treat a variety of diseases. Recent studies have reported that EF has anti-metastatic, anti-angiogenic, anti-bacterial, and anti-oxidant activities, as well as activities against malignant metastatic human cancers. The effect of EF and its components on viruses has not been reported. In the present study, the antiviral activity and mechanism of action of an aqueous extract of EF (WEF) and its components were evaluated in vitro. We found that pretreatment with WEF markedly reduced viral replication, as evaluated using a green fluorescent protein (GFP)-tagged virus (influenza A virus, Newcastle disease virus, and vesicular stomatitis virus) in murine RAW 264.7 macrophage cells. We demonstrated that WEF induces the production of type I IFN including pro-inflammatory cytokines. Additionally, we identified the active anti-viral components of WEF as quercetin, psoralen, and quercitrin. Thus, WEF and its active components are immunomodulators of the innate immune response in murine macrophages, a finding that is potentially useful to developing prophylactic or therapeutic treatments against a range of viruses.",2017 Aug 3,"['Choi, Jang-Gi', 'Lee, Heeeun', 'Hwang, Youn-Hwan', 'Lee, Jong-Soo', 'Cho, Won-Kyung', 'Ma, Jin Yeul']",Front Pharmacol,,,True
ac51af9995edb441f0ce4fdc384908daa6e83675,PMC,TREM2 in Neurodegenerative Diseases,http://dx.doi.org/10.1186/s13024-017-0197-5,PMC5541421,28768545,CC BY,"TREM2 variants have been identified as risk factors for Alzheimer’s disease (AD) and other neurodegenerative diseases (NDDs). Because TREM2 encodes a receptor exclusively expressed on immune cells, identification of these variants conclusively demonstrates that the immune response can play an active role in the pathogenesis of NDDs. These TREM2 variants also confer the highest risk for developing Alzheimer’s disease of any risk factor identified in nearly two decades, suggesting that understanding more about TREM2 function could provide key insights into NDD pathology and provide avenues for novel immune-related NDD biomarkers and therapeutics. The expression, signaling and function of TREM2 in NDDs have been extensively investigated in an effort to understand the role of immune function in disease pathogenesis and progression. We provide a comprehensive review of our current understanding of TREM2 biology, including new insights into the regulation of TREM2 expression, and TREM2 signaling and function across NDDs. While many open questions remain, the current body of literature provides clarity on several issues. While it is still often cited that TREM2 expression is decreased by pro-inflammatory stimuli, it is now clear that this is true in vitro, but inflammatory stimuli in vivo almost universally increase TREM2 expression. Likewise, while TREM2 function is classically described as promoting an anti-inflammatory phenotype, more than half of published studies demonstrate a pro-inflammatory role for TREM2, suggesting that its role in inflammation is much more complex. Finally, these components of TREM2 biology are applied to a discussion of how TREM2 impacts NDD pathologies and the latest assessment of how these findings might be applied to immune-directed clinical biomarkers and therapeutics.",2017 Aug 2,"['Jay, Taylor R.', 'von Saucken, Victoria E.', 'Landreth, Gary E.']",Mol Neurodegener,,,True
05ab8bd6ff732bea31fa673b450d37b58da78c46,PMC,Sensitivity and specificity of a real-time reverse transcriptase polymerase chain reaction detecting feline coronavirus mutations in effusion and serum/plasma of cats to diagnose feline infectious peritonitis,http://dx.doi.org/10.1186/s12917-017-1147-8,PMC5541694,28768514,CC BY,"BACKGROUND: Feline coronavirus (FCoV) exists as two pathotypes, and FCoV spike gene mutations are considered responsible for the pathotypic switch in feline infectious peritonitis (FIP) pathogenesis. The aim of this study was to evaluate sensitivity and specificity of a real-time reverse transcriptase polymerase chain reaction (RT-PCR) specifically designed to detect FCoV spike gene mutations at two nucleotide positions. It was hypothesized that this test would correctly discriminate feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV). METHODS: The study included 63 cats with signs consistent with FIP. FIP was confirmed in 38 cats. Twenty-five control cats were definitively diagnosed with a disease other than FIP. Effusion and/or serum/plasma samples were examined by real-time RT-PCR targeting the two FCoV spike gene fusion peptide mutations M1058 L and S1060A using an allelic discrimination approach. Sensitivity, specificity, negative and positive predictive values including 95% confidence intervals (95% CI) were calculated. RESULTS: FIPV was detected in the effusion of 25/59 cats, one of them being a control cat with chronic kidney disease. A mixed population of FIPV/FECV was detected in the effusion of 2/59 cats; all of them had FIP. RT-PCR was negative or the pathotype could not be determined in 34/59 effusion samples. In effusion, sensitivity was 68.6% (95% CI 50.7–83.2), specificity was 95.8% (95% CI 78.9–99.9). No serum/plasma samples were positive for FIPV. CONCLUSIONS: Although specificity of the test in effusions was high, one false positive result occurred. The use of serum/plasma cannot be recommended due to a low viral load in blood.",2017 Aug 2,"['Felten, Sandra', 'Leutenegger, Christian M.', 'Balzer, Hans-Joerg', 'Pantchev, Nikola', 'Matiasek, Kaspar', 'Wess, Gerhard', 'Egberink, Herman', 'Hartmann, Katrin']",BMC Vet Res,,,True
ff78beee1e6b1052a3578f330c8f820c60411340,PMC,Characterization of Sudan Ebolavirus infection in ferrets,http://dx.doi.org/10.18632/oncotarget.17694,PMC5542265,28545034,CC BY,"Sudan virus (SUDV) outbreaks in Africa are highly lethal; however, the development and testing of novel antivirals and vaccines for this virus has been limited by a lack of suitable animal models. Non-human primates (NHP) remain the gold standard for modeling filovirus disease, but they are not conducive to screening large numbers of experimental compounds and should only be used to test the most promising candidates. Therefore, other smaller animal models are a valuable asset. We have recently developed a guinea-pig adapted SUDV virus that is lethal in guinea pigs. In our current study, we show that ferrets are susceptible to wild-type SUDV, providing a small animal model to directly study clinical isolates, screen experimental anti-SUDV compounds and potentially study viral transmission.",2017 May 8,"['Kroeker, Andrea', 'He, Shihua', 'de La Vega, Marc-Antoine', 'Wong, Gary', 'Embury-Hyatt, Carissa', 'Qiu, Xiangguo']",Oncotarget,,,True
8d95c45acd8f00b91cba82986ef7e6ca2391255c,PMC,Characterization of Sudan Ebolavirus infection in ferrets,http://dx.doi.org/10.18632/oncotarget.17694,PMC5542265,28545034,CC BY,"Sudan virus (SUDV) outbreaks in Africa are highly lethal; however, the development and testing of novel antivirals and vaccines for this virus has been limited by a lack of suitable animal models. Non-human primates (NHP) remain the gold standard for modeling filovirus disease, but they are not conducive to screening large numbers of experimental compounds and should only be used to test the most promising candidates. Therefore, other smaller animal models are a valuable asset. We have recently developed a guinea-pig adapted SUDV virus that is lethal in guinea pigs. In our current study, we show that ferrets are susceptible to wild-type SUDV, providing a small animal model to directly study clinical isolates, screen experimental anti-SUDV compounds and potentially study viral transmission.",2017 May 8,"['Kroeker, Andrea', 'He, Shihua', 'de La Vega, Marc-Antoine', 'Wong, Gary', 'Embury-Hyatt, Carissa', 'Qiu, Xiangguo']",Oncotarget,,,False
e901c7268b77c894b19e9e46a76f53d852f212ab,PMC,Increasing airline travel may facilitate co-circulation of multiple dengue virus serotypes in Asia,http://dx.doi.org/10.1371/journal.pntd.0005694,PMC5542384,28771468,CC BY,"The incidence of dengue has grown dramatically in recent decades worldwide, especially in Southeast Asia and the Americas with substantial transmission in 2014–2015. Yet the mechanisms underlying the spatio-temporal circulation of dengue virus (DENV) serotypes at large geographical scales remain elusive. Here we investigate the co-circulation in Asia of DENV serotypes 1–3 from 1956 to 2015, using a statistical framework that jointly estimates migration history and quantifies potential predictors of viral spatial diffusion, including socio-economic, air transportation and maritime mobility data. We find that the spread of DENV-1, -2 and -3 lineages in Asia is significantly associated with air traffic. Our analyses suggest the network centrality of air traffic hubs such as Thailand and India contribute to seeding dengue epidemics, whilst China, Cambodia, Indonesia, and Singapore may establish viral diffusion links with multiple countries in Asia. Phylogeographic reconstructions help to explain how growing air transportation networks could influence the dynamics of DENV circulation.",2017 Aug 3,"['Tian, Huaiyu', 'Sun, Zhe', 'Faria, Nuno Rodrigues', 'Yang, Jing', 'Cazelles, Bernard', 'Huang, Shanqian', 'Xu, Bo', 'Yang, Qiqi', 'Pybus, Oliver G.', 'Xu, Bing']",PLoS Negl Trop Dis,,,True
46e2d24fe550946db723bc2af9e6d8cc043ce4ab,PMC,Molecular characterization of a novel cryptic virus infecting pigeonpea plants,http://dx.doi.org/10.1371/journal.pone.0181829,PMC5542627,28771507,CC BY,"A new member of the genus Deltapartitivirus was identified containing three dsRNAs with an estimated size of 1.71, 1.49 and 1.43 kb. The dsRNAs were extracted from symptomless pigeonpea [Cajanus cajan (L.) Millspaugh] plants cv. Erra Kandulu. This new virus with 4.64 kb genome was tentatively named Arhar cryptic virus-1 (ArCV-1). The genomic RNAs were amplified and characterized by sequence independent single primer amplification. The dsRNAs shared a highly conserved 16 nt 5’ non-coding region (5’-GATAATGATCCAAGGA-3’). The largest dsRNA (dsRNA-1) was identified as the viral RNA dependent RNA polymerase (replicase), predicted to encode a putative 55.34 kDa protein (P1). The two other smaller dsRNAs (dsRNA-2 and dsRNA-3) predicted to encode for putative capsid proteins of 38.50kDa (P2) and 38.51kDa (P3), respectively. Phylogenetic analysis indicated that ArCV-1 formed a clade together with Fragaria chiloensis cryptic virus, Rosa multiflora cryptic virus and Rose cryptic virus-1, indicating that ArCV-1 could be a new member of the genus Deltapartitivirus. ArCV-1 3D(pol) structure revealed several interesting features. The 3D(pol) in its full-length shares structural similarities with members of the family Caliciviridaeand family Picornaviridae. In addition, fourth dsRNA molecule (dsRNA-2A), not related to ArCV-1 genome, was found in the same plant tissue. The dsRNA-2A (1.6 kb) encodes a protein (P4), with a predicted size of 44.5 kDa. P4 shares similarity with coat protein genes of several cryptic viruses, in particular the bipartite cryptic viruses including Raphanus sativus cryptic virus-3. This is the first report of occurrence of a cryptic virus in pigeonpea plants.",2017 Aug 3,"['Kumar, Surender', 'Subbarao, Burra L.', 'Kumari, Reenu', 'Hallan, Vipin']",PLoS One,,,True
d0fd34148f90e726e4ae52896f0c37146a57cbfc,PMC,Global research trends in West Nile virus from 1943 to 2016: a bibliometric analysis,http://dx.doi.org/10.1186/s12992-017-0284-y,PMC5543434,28774315,CC BY,"BACKGROUND: West Nile virus (WNV) is an emerging infectious disease which is most commonly transmitted to humans through mosquito, and is considered a major public-health problem worldwide. The aim of the current study is to bibliometrically analyze the quantity and quality of publications indexed in Scopus from different countries to reveal the characteristics of global research output regarding WNV. METHODS: This study is a bibliometric analysis based on the Scopus database. This study focused on identifying WNV publication trends with regard to publication year, publication type, prolific countries, language of publication, as well as, prolific journals, citations, and collaboration patterns. RESULTS: A total of 4729 publications were considered in this study, which were published between 1943 and 2016. The annual quantity of literature published before 2000 followed a low rate of research growth; while the quantity of publications after 2000 were published in a stage of rapid development. The country with the greatest number of publications in WNV research field was the USA with 2304 (48.7%) publications, followed by France with 224 (4.7%) publications, and Canada with 222 (4.7%) publications. Contributions from low- and middle-income countries (LMIC) were considerably small, that is, (n = 519 publications; 11%). All publications related to WNV achieved h-index of 140 and were cited 124,222 times. The median [interquartile range] number of citations per article thus amounts to 9 [2-28]. The USA had the highest h-index of 131. Emerging Infectious Diseases is the most productive journal with 227 articles, followed by Journal of Virology with 162 publications. The result designated that Centers for Disease Control and Prevention was ranked the first in terms of publication output, followed by National Center for Emerging and Zoonotic Infectious Diseases. CONCLUSIONS: There is an obvious trend of WNV research after 2000, and countries with high income have more contributions in WNV research field. The research output is low among LMIC. The USA produced the largest number of publications. The Centers for Disease Control and Prevention obtained the leading position of the institutions in terms of publication output. In general, this study not only presents a full view of global WNV research, but also can contribute for future further research in this field.",2017 Aug 3,"Al-Jabi, Samah W.",Global Health,,,True
3f36fd3fb1459eb47b0cd58e5b6fa52529f68695,PMC,The history and epidemiology of Middle East respiratory syndrome corona virus,http://dx.doi.org/10.1186/s40248-017-0101-8,PMC5545842,28794876,CC BY,"Corona viruses cause common cold, and infections caused by corona viruses are generally self-resolving. During the last 4 years, corona viruses have become the most important viruses worldwide because of the occurrence of several recent deaths caused by corona viruses in Saudi Arabia. Spread of the infection occurred worldwide; however, most cases of mortality have occurred in the Middle East. Owing to the predominance of outbreaks in the Middle Eastern countries, the virus was renamed a Middle East respiratory syndrome corona virus (MERS-CoV) by the Corona virus Study Group. The Center for Diseases Control and Prevention and World Health Organization maintain a website that is updated frequently with new cases of MERS-CoV infection. In this review, we describe the history and epidemiology of this novel virus. Studies of the genetics and molecular mechanisms of this virus are expected to facilitate the development of vaccines in the future.",2017 Aug 7,"['Al-Osail, Aisha M.', 'Al-Wazzah, Marwan J.']",Multidiscip Respir Med,,,True
cd4889df1e36fd838d6835714cbf4fdfd7e7e32e,PMC,"Changes in clinical and laboratory features of Kawasaki disease noted over time in Daejeon, Korea",http://dx.doi.org/10.1186/s12969-017-0192-y,PMC5545846,28784161,CC BY,"BACKGROUND: Kawasaki disease (KD) becomes one of the common diseases in Korea. Changes in clinical features and laboratory findings of KD were evaluated over a period of 10 years. METHODS: We reviewed the medical records of KD patients and compared the clinical and laboratory features of two KD patient groups: those admitted from 2000 to 2004 (group A, 284 cases) and those admitted from 2010 to 2014 (group B, 331 cases). RESULTS: There were a total of 615 KD patients (mean age: 29.7 months; male-to-female ratio = 1.6:1), including 228 incomplete KD patients. Incomplete KD patients had milder values in some laboratory indices. The preadmission and total fever durations were longer in group A than in group B. The proportion of incomplete KD was higher in group B, but incidence of coronary artery lesions (CALs) was lower. For laboratory indices, the C-reactive protein and follow-up platelet values were lower, and the hemoglobin and albumin values were higher in group B. The same clinical and laboratory findings were confirmed in the KD subgroups; those with the same fever duration of 5 or 6 days and same ages, those with complete KD, and those with incomplete KD in the two different time periods. CONCLUSIONS: Our findings suggest that clinical features of KD tend to be milder over time and manifest in a higher incidence of incomplete KD, lower incidence of CALs, and less severe laboratory findings in recent KD patients in Korea compared with their historic counterparts.",2017 Aug 7,"['Kil, Hong-Ryang', 'Yu, Jae-Won', 'Lee, Sung-Churl', 'Rhim, Jung-Woo', 'Lee, Kyung-Yil']",Pediatr Rheumatol Online J,,,True
2ce32d388ce40b7b9645329a2a2f0edfff7367ef,PMC,"Swine enteric colibacillosis: diagnosis, therapy and antimicrobial resistance",http://dx.doi.org/10.1186/s40813-017-0063-4,PMC5547460,28794894,CC BY,"Intestinal infection with enterotoxigenic Escherichia coli (ETEC) is an important disease in swine resulting in significant economic losses. Knowledge about the epidemiology, the diagnostic approach and methods of control are of fundamental importance to tackle the disease. The ETEC causing neonatal colibacillosis mostly carry the fimbriae F4 (k88), F5 (k99), F6 (987P) or F41, while the ETEC of post-weaning diarrhoea carry the fimbriae F4 (k88) and F18. These fimbriae adhere to specific receptors on porcine intestinal brush border epithelial cells (enterocytes), starting the process of enteric infection. After this colonization, the bacteria produce one or more enterotoxins inducing diarrhoea, such as the heat stable toxin a (STa), the heat stable toxin b (STb), and the heat labile toxin (LT). A role in the pathogenesis of the disease was demonstrated for these toxins. The diagnosis of enteric colibacillosis is based on the isolation and quantification of the pathogenic E.coli coupled with the demonstration by PCR of the genes encoding for virulence factors (fimbriae and toxins). The diagnostic approach to enteric colibacillosis must consider the differential diagnosis and the potential different causes that can be involved in the outbreak. Among the different methods of control of colibacillosis, the use of antimicrobials is widely practiced and antibiotics are used in two main ways: as prophylactic or metaphylactic treatment to prevent disease and for therapeutic purposes to treat diseased pigs. An accurate diagnosis of enteric colibacillosis needs an appropriate sampling for the isolation and quantification of the ETEC responsible for the outbreak by using semi-quantitative bacteriology. Definitive diagnosis is based on the presence of characteristic lesions and results of bacteriology along with confirmation of appropriate virulence factors to identify the isolated E.coli. It is important to confirm the diagnosis and to perform antimicrobial sensitivity tests because antimicrobial sensitivity varies greatly among E. coli isolates. Growing concern on the increase of antimicrobial resistance force a more rational use of antibiotics and this can be achieved through a correct understanding of the issues related to antibiotic therapy and to the use of antibiotics by both practitioners and farmers.",2017 Aug 8,"Luppi, Andrea",Porcine Health Manag,,,True
92cbe76cf67a384ebfb531cd7d8331d2fde3fb49,PMC,Ecological niche modeling to determine potential niche of Vaccinia virus: a case only study,http://dx.doi.org/10.1186/s12942-017-0100-1,PMC5547515,28784125,CC BY,"BACKGROUND: Emerging and understudied pathogens often lack information that most commonly used analytical tools require, such as negative controls or baseline data; thus, new analytical strategies are needed to analyze transmission patterns and drivers of disease emergence. Zoonotic infections with Vaccinia virus (VACV) were first reported in Brazil in 1999, VACV is an emerging zoonotic Orthopoxvirus, which primarily infects dairy cattle and farmers in close contact with infected cows. Prospective studies of emerging pathogens could provide critical data that would inform public health planning and response to outbreaks. By using the location of 87-recorded outbreaks and publicly available bioclimatic data, we demonstrate one such approach. Using an ecological niche model (ENM) algorithm, we identify the environmental conditions under which VACV outbreaks have occurred, and determine additional locations in two affected countries that may be susceptible to transmission. Further, we show how suitability for the virus responds to different levels of various environmental factors and highlight the most important factors in determining its transmission. METHODS: A literature review was performed and the geospatial coordinates of 87 molecularly confirmed VACV outbreaks in Brazil were identified. An ENM was generated using MaxENT software by combining principal component analysis results of 19 bioclim spatial layers, and 25 randomly selected subsets of the original list of 87 outbreaks. RESULTS: The final ENM predicted all areas where Brazilian outbreaks occurred, one out of five of the Colombian outbreak regions and identified new regions within Brazil that are suitable for transmission based on bioclimatic factors. Further, the most important factors in determining transmission suitability are precipitation of the wettest quarter, annual precipitation, mean temperature of the coldest quarter and mean diurnal range. CONCLUSION: The analyses here provide a means by which to study patterns of an emerging infectious disease and identify regions that are potentially suitable for its transmission, in spite of the paucity of high-quality critical data. Policy and methods for the control of infectious diseases often use a reactionary model, addressing diseases only after significant impact on human health has ensued. The methodology used in the present work allows the identification of areas where disease is likely to appear, which could be used for directed intervention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12942-017-0100-1) contains supplementary material, which is available to authorized users.",2017 Aug 7,"['Quiner, Claire A.', 'Nakazawa, Yoshinori']",Int J Health Geogr,,,True
cfb03431670da70ab0a1cac08df0d45d8f420ad2,PMC,Interleukin-35 on B cell and T cell induction and regulation,http://dx.doi.org/10.1186/s12950-017-0164-5,PMC5547520,28794689,CC BY,"Interleukin (IL)-35 is a relatively newly discovered member of IL-12 cytokine family that is unique in that it is a dimer formed by two subunits. The review documents the structure, secretion and signal transduction of IL-35, the regulation effect of IL-35 on B cells and T cells as well as the adoptive transfer of IL-35+ regulatory B cells (Breg), therapeutic prospects of recombinant IL-35 (rIL-35) and IL-35 regulation role in various diseases. B-cell regulation expands the regulatory range of IL-35 and alters the view that IL-10 is the chief immune mechanism for Breg cells which secrete IL-35. IL-35 induces Breg cells, which then can induce Treg cells. IL-35 also plays an immunomodulatory role in the human body.",2017 Aug 7,"['Huang, Ai', 'Cheng, Lin', 'He, Miao', 'Nie, Jun', 'Wang, Jianjun', 'Jiang, Ke']",J Inflamm (Lond),,,True
7bd10e69b042b04603988ad454d4f94af259b4e6,PMC,Plasmonic silver nanoshells for drug and metabolite detection,http://dx.doi.org/10.1038/s41467-017-00220-4,PMC5548796,28790311,CC BY,"In-vitro metabolite and drug detection rely on designed materials-based analytical platforms, which are universally used in biomedical research and clinical practice. However, metabolic analysis in bio-samples needs tedious sample preparation, due to the sample complexity and low molecular abundance. A further challenge is to construct diagnostic tools. Herein, we developed a platform using silver nanoshells. We synthesized SiO(2)@Ag with tunable shell structures by multi-cycled silver mirror reactions. Optimized nanoshells achieved direct laser desorption/ionization mass spectrometry in 0.5 μL of bio-fluids. We applied these nanoshells for disease diagnosis and therapeutic evaluation. We identified patients with postoperative brain infection through daily monitoring and glucose quantitation in cerebrospinal fluid. We measured drug distribution in blood and cerebrospinal fluid systems and validated the function of blood-brain/cerebrospinal fluid-barriers for pharmacokinetics. Our work sheds light on the design of materials for advanced metabolic analysis and precision diagnostics.",2017 Aug 9,"['Huang, Lin', 'Wan, Jingjing', 'Wei, Xiang', 'Liu, Yu', 'Huang, Jingyi', 'Sun, Xuming', 'Zhang, Ru', 'Gurav, Deepanjali D.', 'Vedarethinam, Vadanasundari', 'Li, Yan', 'Chen, Ruoping', 'Qian, Kun']",Nat Commun,,,False
9853f82beb2aa6e757484232afa30dba030c50fb,PMC,Plasmonic silver nanoshells for drug and metabolite detection,http://dx.doi.org/10.1038/s41467-017-00220-4,PMC5548796,28790311,CC BY,"In-vitro metabolite and drug detection rely on designed materials-based analytical platforms, which are universally used in biomedical research and clinical practice. However, metabolic analysis in bio-samples needs tedious sample preparation, due to the sample complexity and low molecular abundance. A further challenge is to construct diagnostic tools. Herein, we developed a platform using silver nanoshells. We synthesized SiO(2)@Ag with tunable shell structures by multi-cycled silver mirror reactions. Optimized nanoshells achieved direct laser desorption/ionization mass spectrometry in 0.5 μL of bio-fluids. We applied these nanoshells for disease diagnosis and therapeutic evaluation. We identified patients with postoperative brain infection through daily monitoring and glucose quantitation in cerebrospinal fluid. We measured drug distribution in blood and cerebrospinal fluid systems and validated the function of blood-brain/cerebrospinal fluid-barriers for pharmacokinetics. Our work sheds light on the design of materials for advanced metabolic analysis and precision diagnostics.",2017 Aug 9,"['Huang, Lin', 'Wan, Jingjing', 'Wei, Xiang', 'Liu, Yu', 'Huang, Jingyi', 'Sun, Xuming', 'Zhang, Ru', 'Gurav, Deepanjali D.', 'Vedarethinam, Vadanasundari', 'Li, Yan', 'Chen, Ruoping', 'Qian, Kun']",Nat Commun,,,True
0bee52e6477404d2aed60b9ae06ac53bf92660de,PMC,The Hemagglutinin-Esterase Fusion Glycoprotein Is a Primary Determinant of the Exceptional Thermal and Acid Stability of Influenza D Virus,http://dx.doi.org/10.1128/mSphere.00254-17,PMC5549178,28808690,CC BY,"Influenza D virus (IDV) is unique among four types of influenza viruses in that it utilizes cattle as a primary reservoir. The thermal and acid stability of IDV were examined and directly compared with those of influenza A virus (IAV), influenza B virus (IBV), and influenza C virus (ICV). The results of our experiments demonstrated that only IDV had a high residual infectivity (~2.5 log units of 50% tissue culture infective dose [TCID(50)]/ml) after a 60-min exposure to 53°C in solution at a neutral pH, and remarkably, IDV retained this infectivity even after exposure to 53°C for 120 min. Furthermore, the data showed that IDV was extremely resistant to inactivation by low pH. After being treated at pH 3.0 for 30 min, IDV lost only approximately 20% of its original infectiousness, while all other types of influenza viruses were completely inactivated. Finally, replacement of the hemagglutinin (HA) and neuraminidase (NA) proteins of a temperature- and acid-sensitive IAV with the hemagglutinin-esterase fusion (HEF) protein of a stable IDV through a reverse genetic system largely rendered the recombinant IAVs resistant to high-temperature and low-pH treatments. Together, these results indicated that the HEF glycoprotein is a primary determinant of the exceptional temperature and acid tolerance of IDV. Further investigation into the viral entry and fusion mechanism mediated by the intrinsically stable HEF protein of IDV may offer novel insights into how the fusion machinery of influenza viruses evolve to achieve acid and thermal stability, which as a result promotes the potential to transmit across mammal species. IMPORTANCE Influenza D virus (IDV) utilizes cattle as a primary reservoir. Increased outbreaks in pigs and serological evidence of human infection have raised a concern about the potential of IDV adapting to humans. Here, we directly compared IDV’s stability to that of other influenza types (A, B, and C) following prolonged incubation at high temperatures or in a low-pH environment. We found that IDV is the most stable of the four types of influenza viruses. Importantly, we demonstrated that the hemagglutinin-esterase fusion (HEF) protein, which drives the fusion between viral and host cell membranes, is the primary determinant for the high thermal and acid stability of IDV. Considering that there is a link between the acid stability of the hemagglutinin protein of influenza A virus and its cross-species transmission, further investigation of the mechanism of HEF-directed viral tolerance may offer novel insights into tissue tropism and cross-species transmission of influenza viruses.",2017 Aug 9,"['Yu, Jieshi', 'Hika, Busha', 'Liu, Runxia', 'Sheng, Zizhang', 'Hause, Ben M.', 'Li, Feng', 'Wang, Dan']",mSphere,,,True
cdaa06e4dc1b2114a9440409758fb22c1e62a2d9,PMC,Optimization and validation of sample preparation for metagenomic sequencing of viruses in clinical samples,http://dx.doi.org/10.1186/s40168-017-0317-z,PMC5549297,28789678,CC BY,"BACKGROUND: Sequence-specific PCR is the most common approach for virus identification in diagnostic laboratories. However, as specific PCR only detects pre-defined targets, novel virus strains or viruses not included in routine test panels will be missed. Recently, advances in high-throughput sequencing allow for virus-sequence-independent identification of entire virus populations in clinical samples, yet standardized protocols are needed to allow broad application in clinical diagnostics. Here, we describe a comprehensive sample preparation protocol for high-throughput metagenomic virus sequencing using random amplification of total nucleic acids from clinical samples. RESULTS: In order to optimize metagenomic sequencing for application in virus diagnostics, we tested different enrichment and amplification procedures on plasma samples spiked with RNA and DNA viruses. A protocol including filtration, nuclease digestion, and random amplification of RNA and DNA in separate reactions provided the best results, allowing reliable recovery of viral genomes and a good correlation of the relative number of sequencing reads with the virus input. We further validated our method by sequencing a multiplexed viral pathogen reagent containing a range of human viruses from different virus families. Our method proved successful in detecting the majority of the included viruses with high read numbers and compared well to other protocols in the field validated against the same reference reagent. Our sequencing protocol does work not only with plasma but also with other clinical samples such as urine and throat swabs. CONCLUSIONS: The workflow for virus metagenomic sequencing that we established proved successful in detecting a variety of viruses in different clinical samples. Our protocol supplements existing virus-specific detection strategies providing opportunities to identify atypical and novel viruses commonly not accounted for in routine diagnostic panels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40168-017-0317-z) contains supplementary material, which is available to authorized users.",2017 Aug 8,"['Lewandowska, Dagmara W.', 'Zagordi, Osvaldo', 'Geissberger, Fabienne-Desirée', 'Kufner, Verena', 'Schmutz, Stefan', 'Böni, Jürg', 'Metzner, Karin J.', 'Trkola, Alexandra', 'Huber, Michael']",Microbiome,,,False
23393085181dbde8039e7123f35b67d4b2e9f6ba,PMC,Optimization and validation of sample preparation for metagenomic sequencing of viruses in clinical samples,http://dx.doi.org/10.1186/s40168-017-0317-z,PMC5549297,28789678,CC BY,"BACKGROUND: Sequence-specific PCR is the most common approach for virus identification in diagnostic laboratories. However, as specific PCR only detects pre-defined targets, novel virus strains or viruses not included in routine test panels will be missed. Recently, advances in high-throughput sequencing allow for virus-sequence-independent identification of entire virus populations in clinical samples, yet standardized protocols are needed to allow broad application in clinical diagnostics. Here, we describe a comprehensive sample preparation protocol for high-throughput metagenomic virus sequencing using random amplification of total nucleic acids from clinical samples. RESULTS: In order to optimize metagenomic sequencing for application in virus diagnostics, we tested different enrichment and amplification procedures on plasma samples spiked with RNA and DNA viruses. A protocol including filtration, nuclease digestion, and random amplification of RNA and DNA in separate reactions provided the best results, allowing reliable recovery of viral genomes and a good correlation of the relative number of sequencing reads with the virus input. We further validated our method by sequencing a multiplexed viral pathogen reagent containing a range of human viruses from different virus families. Our method proved successful in detecting the majority of the included viruses with high read numbers and compared well to other protocols in the field validated against the same reference reagent. Our sequencing protocol does work not only with plasma but also with other clinical samples such as urine and throat swabs. CONCLUSIONS: The workflow for virus metagenomic sequencing that we established proved successful in detecting a variety of viruses in different clinical samples. Our protocol supplements existing virus-specific detection strategies providing opportunities to identify atypical and novel viruses commonly not accounted for in routine diagnostic panels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40168-017-0317-z) contains supplementary material, which is available to authorized users.",2017 Aug 8,"['Lewandowska, Dagmara W.', 'Zagordi, Osvaldo', 'Geissberger, Fabienne-Desirée', 'Kufner, Verena', 'Schmutz, Stefan', 'Böni, Jürg', 'Metzner, Karin J.', 'Trkola, Alexandra', 'Huber, Michael']",Microbiome,,,True
ab1ac4f7b9c57dad5e3d61f72e8e3d552059fa09,PMC,Synergistic inhibition of human cytomegalovirus replication by interferon-alpha/beta and interferon-gamma,http://dx.doi.org/10.1186/1743-422X-2-14,PMC554982,15727684,CC BY,"BACKGROUND: Recent studies have shown that gamma interferon (IFN-γ) synergizes with the innate IFNs (IFN-α and IFN-β) to inhibit herpes simplex virus type 1 (HSV-1) replication in vitro. To determine whether this phenomenon is shared by other herpesviruses, we investigated the effects of IFNs on human cytomegalovirus (HCMV) replication. RESULTS: We have found that as with HSV-1, IFN-γ synergizes with the innate IFNs (IFN-α/β) to potently inhibit HCMV replication in vitro. While pre-treatment of human foreskin fibroblasts (HFFs) with IFN-α, IFN-β or IFN-γ alone inhibited HCMV plaque formation by ~30 to 40-fold, treatment with IFN-α and IFN-γ or IFN-β and IFN-γ inhibited HCMV plaque formation by 163- and 662-fold, respectively. The generation of isobole plots verified that the observed inhibition of HCMV plaque formation and replication in HFFs by IFN-α/β and IFN-γ was a synergistic interaction. Additionally, real-time PCR analyses of the HCMV immediate early (IE) genes (IE1 and IE2) revealed that IE mRNA expression was profoundly decreased in cells stimulated with IFN-α/β and IFN-γ (~5-11-fold) as compared to vehicle-treated cells. Furthermore, decreased IE mRNA expression was accompanied by a decrease in IE protein expression, as demonstrated by western blotting and immunofluorescence. CONCLUSION: These findings suggest that IFN-α/β and IFN-γ synergistically inhibit HCMV replication through a mechanism that may involve the regulation of IE gene expression. We hypothesize that IFN-γ produced by activated cells of the adaptive immune response may potentially synergize with endogenous type I IFNs to inhibit HCMV dissemination in vivo.",2005 Feb 23,"['Sainz, Bruno', 'LaMarca, Heather L', 'Garry, Robert F', 'Morris, Cindy A']",Virol J,,,True
a59fdbfef640d08b4729060ee005ff35f87c0a40,PMC,Viral and bacterial upper respiratory tract infection in hospital health care workers over time and association with symptoms,http://dx.doi.org/10.1186/s12879-017-2649-5,PMC5550936,28793861,CC BY,"BACKGROUND: Bacterial colonisation of the respiratory tract is commonly described and usually thought to be of no clinical significance. The aim of this study was to examine the presence and significance of bacteria and viruses in the upper respiratory tract of healthcare workers (HCWs), and association with respiratory symptoms. METHODS: A prospective cohort study was conducted in China and 223 HCWs were recruited from fever clinics and respiratory, paediatric, emergency/Intensive medication wards. Participants were followed over 4 weeks (7th May 2015 to 4th June 2015) for development of clinical respiratory illness (CRI). Nasopharyngeal swabs were obtained at baseline and at the end of the study. The primary endpoints were laboratory-confirmed bacterial colonisation and viral respiratory infection. Rates of the following infections in symptomatic and asymptomatic participants were compared at the start or end of the study; 1) all bacterial/viral infections, 2) bacterial infection and bacterial-viral co-infections, excluding virus only infections, and 3) only bacterial infections. RESULTS: Bacterial colonisation was identified in 88% (196/223) of participants at the start or end of the study. Among these participants, 66% (148/223) had only bacterial colonisation while 22% (48/223) had co-infection with a virus. Bacteria were isolated from 170 (76.2%) participants at baseline and 127 (57%) participants at the end of the study. Laboratory confirmed viral infections were identified in 53 (23.8%) participants - 35 (15.7%) at the baseline and 20 (9.0%) at the end of the study. CRI symptoms were recorded in 12 participants (4.5%) and all had a positive bacterium isolation at baseline (n = 11) or end of the study (n = 1). Among asymptomatic participants, 187 (87%) had bacterial colonisation or bacterial/viral co-infection at baseline or end of the study. Viruses were also isolated from 5 (2.4%) asymptomatic cases. Rates of all infection outcomes were higher in symptomatic participants, however differences were not statistically significant. CONCLUSION: We isolated high rates of bacteria and viruses in the upper respiratory tract of hospital HCWs, which may reflect greater exposure to respiratory infections in the hospital. Although respiratory infections are mostly symptomatic, the association between bacterial colonization and symptomatic illness is not clear. In the healthcare setting, HCWs may acquire and transmit infection to patients and other HCWs around them. Larger studies are required to explore ongoing occupational risk of respiratory infection in hospitals HCWs.",2017 Aug 9,"['Raina MacIntyre, C.', 'Chughtai, Abrar Ahmad', 'Zhang, Yi', 'Seale, Holly', 'Yang, Peng', 'Chen, Joshua', 'Pan, Yang', 'Zhang, Daitao', 'Wang, Quanyi']",BMC Infect Dis,,,True
e164fa160155af75c4fc98397014ef055030950e,PMC,Anticipating the emergence of infectious diseases,http://dx.doi.org/10.1098/rsif.2017.0115,PMC5550966,28679666,CC BY,"In spite of medical breakthroughs, the emergence of pathogens continues to pose threats to both human and animal populations. We present candidate approaches for anticipating disease emergence prior to large-scale outbreaks. Through use of ideas from the theories of dynamical systems and stochastic processes we develop approaches which are not specific to a particular disease system or model, but instead have general applicability. The indicators of disease emergence detailed in this paper can be classified into two parallel approaches: a set of early-warning signals based around the theory of critical slowing down and a likelihood-based approach. To test the reliability of these two approaches we contrast theoretical predictions with simulated data. We find good support for our methods across a range of different model structures and parameter values.",2017 Jul 5,"['Brett, Tobias S.', 'Drake, John M.', 'Rohani, Pejman']",J R Soc Interface,,,True
bbf36eb3250211e0c223d0c2a9c41abcaa32d11a,PMC,Novel in vitro booster vaccination to rapidly generate antigen-specific human monoclonal antibodies,http://dx.doi.org/10.1084/jem.20170633,PMC5551578,28739603,CC BY,"Vaccines remain the most effective tool to prevent infectious diseases. Here, we introduce an in vitro booster vaccination approach that relies on antigen-dependent activation of human memory B cells in culture. This stimulation induces antigen-specific B cell proliferation, differentiation of B cells into plasma cells, and robust antibody secretion after a few days of culture. We validated this strategy using cells from healthy donors to retrieve human antibodies against tetanus toxoid and influenza hemagglutinin (HA) from H1N1 and newly emergent subtypes such as H5N1 and H7N9. Anti-HA antibodies were cross-reactive against multiple subtypes, and some showed neutralizing activity. Although these antibodies may have arisen as a result of previous influenza infection, we also obtained gp120-reactive antibodies from non–HIV-infected donors, indicating that we can generate antibodies without prior antigenic exposure. Overall, our novel approach can be used to rapidly produce therapeutic antibodies and has the potential to assess the immunogenicity of candidate antigens, which could be exploited in future vaccine development.",2017 Aug 7,"['Sanjuan Nandin, Irene', 'Fong, Carol', 'Deantonio, Cecilia', 'Torreno-Pina, Juan A.', 'Pecetta, Simone', 'Maldonado, Paula', 'Gasparrini, Francesca', 'Ordovas-Montanes, Jose', 'Kazer, Samuel W.', 'Kjaer, Svend', 'Borley, Daryl W.', 'Nair, Usha', 'Coleman, Julia A.', 'Lingwood, Daniel', 'Shalek, Alex K.', 'Meffre, Eric', 'Poignard, Pascal', 'Burton, Dennis R.', 'Batista, Facundo D.']",J Exp Med,,,True
2a4a771211ad45b642c1a5b19b789f0e35aa0d23,PMC,Novel in vitro booster vaccination to rapidly generate antigen-specific human monoclonal antibodies,http://dx.doi.org/10.1084/jem.20170633,PMC5551578,28739603,CC BY,"Vaccines remain the most effective tool to prevent infectious diseases. Here, we introduce an in vitro booster vaccination approach that relies on antigen-dependent activation of human memory B cells in culture. This stimulation induces antigen-specific B cell proliferation, differentiation of B cells into plasma cells, and robust antibody secretion after a few days of culture. We validated this strategy using cells from healthy donors to retrieve human antibodies against tetanus toxoid and influenza hemagglutinin (HA) from H1N1 and newly emergent subtypes such as H5N1 and H7N9. Anti-HA antibodies were cross-reactive against multiple subtypes, and some showed neutralizing activity. Although these antibodies may have arisen as a result of previous influenza infection, we also obtained gp120-reactive antibodies from non–HIV-infected donors, indicating that we can generate antibodies without prior antigenic exposure. Overall, our novel approach can be used to rapidly produce therapeutic antibodies and has the potential to assess the immunogenicity of candidate antigens, which could be exploited in future vaccine development.",2017 Aug 7,"['Sanjuan Nandin, Irene', 'Fong, Carol', 'Deantonio, Cecilia', 'Torreno-Pina, Juan A.', 'Pecetta, Simone', 'Maldonado, Paula', 'Gasparrini, Francesca', 'Ordovas-Montanes, Jose', 'Kazer, Samuel W.', 'Kjaer, Svend', 'Borley, Daryl W.', 'Nair, Usha', 'Coleman, Julia A.', 'Lingwood, Daniel', 'Shalek, Alex K.', 'Meffre, Eric', 'Poignard, Pascal', 'Burton, Dennis R.', 'Batista, Facundo D.']",J Exp Med,,,False
0749cab30d660b29d52b5346b02773a3f36fda0d,PMC,The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases,http://dx.doi.org/10.1371/journal.ppat.1006546,PMC5552337,28759649,CC BY,"Infection by enveloped coronaviruses (CoVs) initiates with viral spike (S) proteins binding to cellular receptors, and is followed by proteolytic cleavage of receptor-bound S proteins, which prompts S protein-mediated virus-cell membrane fusion. Infection therefore requires close proximity of receptors and proteases. We considered whether tetraspanins, scaffolding proteins known to facilitate CoV infections, hold receptors and proteases together on cell membranes. Using knockout cell lines, we found that the tetraspanin CD9, but not the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4 (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease (TTSP) member TMPRSS2, a CoV-activating protease. This CD9-facilitated condensation of receptors and proteases allowed MERS-CoV pseudoviruses to enter cells rapidly and efficiently. Without CD9, MERS-CoV viruses were not activated by TTSPs, and they trafficked into endosomes to be cleaved much later and less efficiently by cathepsins. Thus, we identified DPP4:CD9:TTSP as the protein complexes necessary for early, efficient MERS-CoV entry. To evaluate the importance of these complexes in an in vivo CoV infection model, we used recombinant Adenovirus 5 (rAd5) vectors to express human DPP4 in mouse lungs, thereby sensitizing the animals to MERS-CoV infection. When the rAd5-hDPP4 vectors co-expressed small RNAs silencing Cd9 or Tmprss2, the animals were significantly less susceptible, indicating that CD9 and TMPRSS2 facilitated robust in vivo MERS-CoV infection of mouse lungs. Furthermore, the S proteins of virulent mouse-adapted MERS-CoVs acquired a CD9-dependent cell entry character, suggesting that CD9 is a selective agent in the evolution of CoV virulence.",2017 Jul 31,"['Earnest, James T.', 'Hantak, Michael P.', 'Li, Kun', 'McCray, Paul B.', 'Perlman, Stanley', 'Gallagher, Tom']",PLoS Pathog,,,True
970253c7b4ba9e8d8e33f39cd13a21b2b1ae2c35,PMC,"Cross-species transmission potential between wild pigs, livestock, poultry, wildlife, and humans: implications for disease risk management in North America",http://dx.doi.org/10.1038/s41598-017-07336-z,PMC5552697,28798293,CC BY,"Cross-species disease transmission between wildlife, domestic animals and humans is an increasing threat to public and veterinary health. Wild pigs are increasingly a potential veterinary and public health threat. Here we investigate 84 pathogens and the host species most at risk for transmission with wild pigs using a network approach. We assess the risk to agricultural and human health by evaluating the status of these pathogens and the co-occurrence of wild pigs, agriculture and humans. We identified 34 (87%) OIE listed swine pathogens that cause clinical disease in livestock, poultry, wildlife, and humans. On average 73% of bacterial, 39% of viral, and 63% of parasitic pathogens caused clinical disease in other species. Non-porcine livestock in the family Bovidae shared the most pathogens with swine (82%). Only 49% of currently listed OIE domestic swine diseases had published wild pig surveillance studies. The co-occurrence of wild pigs and farms increased annually at a rate of 1.2% with as much as 57% of all farms and 77% of all agricultural animals co-occurring with wild pigs. The increasing co-occurrence of wild pigs with livestock and humans along with the large number of pathogens shared is a growing risk for cross-species transmission.",2017 Aug 10,"['Miller, Ryan S.', 'Sweeney, Steven J.', 'Slootmaker, Chris', 'Grear, Daniel A.', 'Di Salvo, Paul A.', 'Kiser, Deborah', 'Shwiff, Stephanie A.']",Sci Rep,,,True
1a5f2c3f99d3607bf9170dcda0c54bc1b4400f6a,PMC,"Cross-species transmission potential between wild pigs, livestock, poultry, wildlife, and humans: implications for disease risk management in North America",http://dx.doi.org/10.1038/s41598-017-07336-z,PMC5552697,28798293,CC BY,"Cross-species disease transmission between wildlife, domestic animals and humans is an increasing threat to public and veterinary health. Wild pigs are increasingly a potential veterinary and public health threat. Here we investigate 84 pathogens and the host species most at risk for transmission with wild pigs using a network approach. We assess the risk to agricultural and human health by evaluating the status of these pathogens and the co-occurrence of wild pigs, agriculture and humans. We identified 34 (87%) OIE listed swine pathogens that cause clinical disease in livestock, poultry, wildlife, and humans. On average 73% of bacterial, 39% of viral, and 63% of parasitic pathogens caused clinical disease in other species. Non-porcine livestock in the family Bovidae shared the most pathogens with swine (82%). Only 49% of currently listed OIE domestic swine diseases had published wild pig surveillance studies. The co-occurrence of wild pigs and farms increased annually at a rate of 1.2% with as much as 57% of all farms and 77% of all agricultural animals co-occurring with wild pigs. The increasing co-occurrence of wild pigs with livestock and humans along with the large number of pathogens shared is a growing risk for cross-species transmission.",2017 Aug 10,"['Miller, Ryan S.', 'Sweeney, Steven J.', 'Slootmaker, Chris', 'Grear, Daniel A.', 'Di Salvo, Paul A.', 'Kiser, Deborah', 'Shwiff, Stephanie A.']",Sci Rep,,,True
e0494e196f7f6d783c5c05ac339d19934c000c1f,PMC,Establishment and Application of a Universal Coronavirus Screening Method Using MALDI-TOF Mass Spectrometry,http://dx.doi.org/10.3389/fmicb.2017.01510,PMC5552709,28848521,CC BY,"There are four human coronaviruses (HCoVs), distributed worldwide, that are associated with a range of respiratory symptoms. The discovery of severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV shows that HCoVs pose a significant threat to human health. Our work aims to develop a sensitive method (mCoV-MS) which can not only identify known HCoVs accurately, but also have the ability to provide clues for the emerging HCoVs. The method was performed using a MassARRAY matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) system. We developed a 17-plex analysis to detect six HCoVs in Panel A and another 17-plex analysis to detect Alphacoronavirus and Betacoronavirus in Panel B. All tested primers and probes for the mCoV-MS method were effective, with no cross-reactivity observed with other common respiratory viruses. To confirm the usefulness of the mCoV-MS method we screened 384 pharyngeal and/or anal swab samples collected from bats/rodents, and 131 nasal and throat swabs from human patients. The results showed good concordance with the results of metagenomic analysis or PCR-sequencing. The validation test showed mCoV-MS method can detect potentially pathogenic CoVs in Alphacoronavirus and Betacoronavirus and provide convincingly phylogenetic evidences about unknown CoVs. The mCoV-MS method is a sensitive assay that is relatively simple to carry out. We propose that this method be used to complement next generation sequencing technology for large-scale screening studies.",2017 Aug 9,"['Xiu, Leshan', 'Zhang, Chi', 'Wu, Zhiqiang', 'Peng, Junping']",Front Microbiol,,,True
ba1a34ae67fb2dcd9ad6cdf6d5b5e1fc32202839,PMC,Cellular RNA Helicase DDX1 Is Involved in Transmissible Gastroenteritis Virus nsp14-Induced Interferon-Beta Production,http://dx.doi.org/10.3389/fimmu.2017.00940,PMC5552718,28848548,CC BY,"Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus (CoV) of porcine, causes lethal watery diarrhea and severe dehydration in piglets and leads to severe economic losses in the swine industry. Unlike most CoVs that antagonize type I interferon (IFN) production, previous studies showed that TGEV infection induces IFN-I production both in vivo and in vitro. However, the underlying mechanism(s) remain largely unknown. In this study, we found that TGEV infection significantly facilitated IFN-β production as well as activation of the transcription factors IFN regulatory factor 3 (IRF3) and nuclear factor-kappaB (NF-κB) in porcine kidney (PK-15) cells. Screening of TGEV-encoded proteins demonstrated that non-structural protein 14 (nsp14) was the most potent IFN-β inducer and induced IFN-β production mainly by activating NF-κB but not IRF3. Further analysis showed that nsp14 interacted with DDX1, a member of the DExD/H helicase family. Knockdown of DDX1 by specific small interfering RNA (siRNA) significantly decreased nsp14-induced IFN-β production and NF-κB activation. Furthermore, TGEV-induced IFN-β production and IFN-stimulated gene (ISG) expression were decreased in cells transfected with DDX1-specific siRNA, indicating the vital role of DDX1 to TGEV-induced IFN-β responses. In summary, our data revealed a potential coactivator role of host RNA helicase DDX1 to the induction of IFN-β response initiated by TGEV and demonstrated that nsp14 is an important IFN inducer among the TGEV-encoded proteins.",2017 Aug 9,"['Zhou, Yanrong', 'Wu, Wei', 'Xie, Lilan', 'Wang, Dang', 'Ke, Qiyun', 'Hou, Zhenzhen', 'Wu, Xiaoli', 'Fang, Ying', 'Chen, Huanchun', 'Xiao, Shaobo', 'Fang, Liurong']",Front Immunol,,,True
2990612686e9b3dc6819d62a2daeec9c857a98e9,PMC,Does the human immune system ever really become “senescent”?,http://dx.doi.org/10.12688/f1000research.11297.1,PMC5553082,28868129,CC BY,"Like all somatic tissues, the human immune system changes with age. This is believed to result in an increased frequency of, and susceptibility to, infectious disease and to contribute to a wide range of non-communicable age-associated diseases in later life, especially cancer, cardiovascular disease, and autoimmunity. The majority of studies addressing immune ageing has been cross-sectional, but limited longitudinal studies are contributing to a better understanding of age-associated changes, as opposed to differences, and their clinical relevance. However, intriguing differences are emerging that implicate highly context-dependent immune ageing processes, mitigating against current generalisations concerning human immunosenescence and indicating the necessity for detailed comparisons of different populations, even those that would appear quite similar at first glance.",2017 Aug 4,"Pawelec, Graham",F1000Res,,,True
5bff4ea8641b22fa07590fce75e19dccf9f75548,PMC,Alterations in lipid profile in neonatal calves affected by diarrhea,http://dx.doi.org/10.14202/vetworld.2017.786-789,PMC5553148,28831223,CC BY,"AIM: The aim of this study was to determine the alterations in the lipid profile, plasma alkaline phosphatase (ALP) activity, total and direct bilirubin levels of neonatal calves with diarrhea. MATERIALS AND METHODS: A total of 25 calves with diarrhea as experimental group and 10 healthy calves as control group, 1-30 days old, were enrolled in the study. Blood samples were collected from jugular vein in tubes with anticoagulant agent to evaluate the concentration of triglycerides, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), ALP, total and direct bilirubin. Very low-density lipoprotein-cholesterol (VLDL-C) and low-density lipoprotein-cholesterol (LDL-C) levels were calculated according to the Friedewald formula. RESULTS: Significant increases in the plasma levels of ALP (p<0.05), total and direct bilirubin, triglycerides, and VLDL-C (p<0.01) were determined, whereas significant decreases in the levels of total cholesterol, HDL-C and LDL-C (p<0.01) were observed in neonatal calves with diarrhea. CONCLUSION: According to the findings of this study, liver functions impaired and, therefore, lipid profile is affected negatively in neonatal calves with diarrhea.",2017 Jul 16,"['Bozukluhan, K.', 'Merhan, O.', 'Gokce, H. I.', 'Deveci, H. A.', 'Gokce, G.', 'Ogun, M.', 'Marasli, S.']",Vet World,,,True
8624ce91f316d2aae5c09273f9308cc08ffcc25c,PMC,Role of transcription regulatory sequence in regulation of gene expression and replication of porcine reproductive and respiratory syndrome virus,http://dx.doi.org/10.1186/s13567-017-0445-2,PMC5553793,28797297,CC BY,"In order to gain insight into the role of the transcription regulatory sequences (TRSs) in the regulation of gene expression and replication of porcine reproductive and respiratory syndrome virus (PRRSV), the enhanced green fluorescent protein (EGFP) gene, under the control of the different structural gene TRSs, was inserted between the N gene and 3′-UTR of the PRRSV genome and EGFP expression was analyzed for each TRS. TRSs of all the studied structural genes of PRRSV positively modulated EGFP expression at different levels. Among the TRSs analyzed, those of GP2, GP5, M, and N genes highly enhanced EGFP expression without altering replication of PRRSV. These data indicated that structural gene TRSs could be an extremely useful tool for foreign gene expression using PRRSV as a vector. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-017-0445-2) contains supplementary material, which is available to authorized users.",2017 Aug 10,"['Wang, Chengbao', 'Meng, Han', 'Gao, Yujin', 'Gao, Hui', 'Guo, Kangkang', 'Almazan, Fernando', 'Sola, Isabel', 'Enjuanes, Luis', 'Zhang, Yanming', 'Abrahamyan, Levon']",Vet Res,,,True
77dc09841a62d92ba5a40d4f848f34e3c4e27713,PMC,Social contact patterns relevant to the spread of respiratory infectious diseases in Hong Kong,http://dx.doi.org/10.1038/s41598-017-08241-1,PMC5554254,28801623,CC BY,"The spread of many respiratory infections is determined by contact patterns between infectious and susceptible individuals in the population. There are no published data for quantifying social contact patterns relevant to the spread of respiratory infectious diseases in Hong Kong which is a hotspot for emerging infectious diseases due to its high population density and connectivity in the air transportation network. We adopted a commonly used diary-based design to conduct a social contact survey in Hong Kong in 2015/16 using both paper and online questionnaires. Participants using paper questionnaires reported more contacts and longer contact duration than those using online questionnaires. Participants reported 13 person-hours of contact and 8 contacts per day on average, which decreased over age but increased with household size, years of education and income level. Prolonged and frequent contacts, and contacts at home, school and work were more likely to involve physical contacts. Strong age-assortativity was observed in all age groups. We evaluated the characteristics of social contact patterns relevant to the spread of respiratory infectious diseases in Hong Kong. Our findings could help to improve the design of future social contact surveys, parameterize transmission models of respiratory infectious diseases, and inform intervention strategies based on model outputs.",2017 Aug 11,"['Leung, Kathy', 'Jit, Mark', 'Lau, Eric H. Y.', 'Wu, Joseph T.']",Sci Rep,,,True
2b6ea0603deab65ea1e0ddf4367985f6061bac9b,PMC,Social contact patterns relevant to the spread of respiratory infectious diseases in Hong Kong,http://dx.doi.org/10.1038/s41598-017-08241-1,PMC5554254,28801623,CC BY,"The spread of many respiratory infections is determined by contact patterns between infectious and susceptible individuals in the population. There are no published data for quantifying social contact patterns relevant to the spread of respiratory infectious diseases in Hong Kong which is a hotspot for emerging infectious diseases due to its high population density and connectivity in the air transportation network. We adopted a commonly used diary-based design to conduct a social contact survey in Hong Kong in 2015/16 using both paper and online questionnaires. Participants using paper questionnaires reported more contacts and longer contact duration than those using online questionnaires. Participants reported 13 person-hours of contact and 8 contacts per day on average, which decreased over age but increased with household size, years of education and income level. Prolonged and frequent contacts, and contacts at home, school and work were more likely to involve physical contacts. Strong age-assortativity was observed in all age groups. We evaluated the characteristics of social contact patterns relevant to the spread of respiratory infectious diseases in Hong Kong. Our findings could help to improve the design of future social contact surveys, parameterize transmission models of respiratory infectious diseases, and inform intervention strategies based on model outputs.",2017 Aug 11,"['Leung, Kathy', 'Jit, Mark', 'Lau, Eric H. Y.', 'Wu, Joseph T.']",Sci Rep,,,True
7aa3c6793455d0748b58fc6ff75ab336b2863c6c,PMC,Orientation determination by wavelets matching for 3D reconstruction of very noisy electron microscopic virus images,http://dx.doi.org/10.1186/1472-6807-5-5,PMC555555,15743519,CC BY,"BACKGROUND: In order to perform a 3D reconstruction of electron microscopic images of viruses, it is necessary to determine the orientation (Euler angels) of the 2D projections of the virus. The projections containing high resolution information are usually very noisy. This paper proposes a new method, based on weighted-projection matching in wavelet space for virus orientation determination. In order to speed the retrieval of the best match between projections from a model and real virus particle, a hierarchical correlation matching method is also proposed. RESULTS: A data set of 600 HSV-1 capsid particle images in different orientations was used to test the proposed method. An initial model of about 40 Å resolutions was used to generate projections of an HSV-1 capsid. Results show that a significant improvement, in terms of accuracy and speed, is obtained for the initial orientation estimates of noisy herpes virus images. For the bacteriophage (P22), the proposed method gave the correct reconstruction compared to the model, while the classical method failed to resolve the correct orientations of the smooth spherical P22 viruses. CONCLUSION: This paper introduces a new method for orientation determination of low contrast images and highly noisy virus particles. This method is based on weighted projection matching in wavelet space, which increases the accuracy of the orientations. A hierarchical implementation of this method increases the speed of orientation determination. The estimated number of particles needed for a higher resolution reconstruction increased exponentially. For a 6 Å resolution reconstruction of the HSV virus, 50,000 particles are necessary. The results show that the proposed method reduces the amount of data needed in a reconstruction by at least 50 %. This may result in savings 2 to 3 man-years invested in acquiring images from the microscope and data processing. Furthermore, the proposed method is able to determine orientations for some difficult particles like P22 with accuracy and consistency. Recently a low PH sindbis capsid was determined with the proposed method, where other methods based on the common line fail.",2005 Mar 2,"Saad, Ali Samir",BMC Struct Biol,,,True
7bf3a8d040b9b6c3542b38c02f8eabbe971b2eb8,PMC,Proteomics informed by transcriptomics for characterising differential cellular susceptibility to Nelson Bay orthoreovirus infection,http://dx.doi.org/10.1186/s12864-017-3994-x,PMC5556373,28806913,CC BY,"BACKGROUND: Nelson Bay orthoreovirus (NBV) is a fusogenic bat borne virus with an unknown zoonotic potential. Previous studies have shown that NBV can infect and replicate in a wide variety of cell types derived from their natural host (bat), as well as from human, mouse and monkey. Within permissive cells, NBV induced significant cytopathic effects characterised by cell-cell fusion and syncytia formation. To understand the molecular events that underpin NBV infection we examined the host transcriptome and proteome response of two cell types, derived from bat (PaKiT03) and mouse (L929), to characterise differential cellular susceptibility to NBV. RESULTS: Despite significant differences in NBV replication and cytopathic effects in the L929 and PaKiT03 cells, the host response was remarkably similar in these cells. At both the transcriptome and proteome level, the host response was dominated by IFN production and signalling pathways. The majority of proteins up-regulated in L929 and PaKiT03 cells were also up-regulated at the mRNA (gene) level, and included many important IFN stimulated genes. Further functional experimentation demonstrated that stimulating IFN signalling prior to infection, significantly reduced NBV replication in PaKiT03 cells. Moreover, inhibiting IFN signalling (through specific siRNAs) increased NBV replication in L929 cells. In line with the significant cytopathic effects seen in PaKiT03 cells, we also observed a down-regulation of genes involved in cell-cell junctions, which may be related to the fusogenic effects of NBV. CONCLUSIONS: This study provides new multi-dimensional insights into the host response of mammalian cells to NBV infection. We show that IFN activity is capable of reducing NBV replication, although it is unlikely that this is solely responsible for the reduced replication of NBV in L929 cells. The molecular events that underpin the fusogenic cytopathic effects described here will prove valuable for identifying potential therapeutic targets against fusogenic orthoreovirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3994-x) contains supplementary material, which is available to authorized users.",2017 Aug 14,"['Mok, Lawrence', 'Wynne, James W.', 'Tachedjian, Mary', 'Shiell, Brian', 'Ford, Kris', 'Matthews, David A.', 'Bacic, Antony', 'Michalski, Wojtek P.']",BMC Genomics,,,False
74287c692dfddb6f55ef5d29e3bc2e5dcf6725ea,PMC,Proteomics informed by transcriptomics for characterising differential cellular susceptibility to Nelson Bay orthoreovirus infection,http://dx.doi.org/10.1186/s12864-017-3994-x,PMC5556373,28806913,CC BY,"BACKGROUND: Nelson Bay orthoreovirus (NBV) is a fusogenic bat borne virus with an unknown zoonotic potential. Previous studies have shown that NBV can infect and replicate in a wide variety of cell types derived from their natural host (bat), as well as from human, mouse and monkey. Within permissive cells, NBV induced significant cytopathic effects characterised by cell-cell fusion and syncytia formation. To understand the molecular events that underpin NBV infection we examined the host transcriptome and proteome response of two cell types, derived from bat (PaKiT03) and mouse (L929), to characterise differential cellular susceptibility to NBV. RESULTS: Despite significant differences in NBV replication and cytopathic effects in the L929 and PaKiT03 cells, the host response was remarkably similar in these cells. At both the transcriptome and proteome level, the host response was dominated by IFN production and signalling pathways. The majority of proteins up-regulated in L929 and PaKiT03 cells were also up-regulated at the mRNA (gene) level, and included many important IFN stimulated genes. Further functional experimentation demonstrated that stimulating IFN signalling prior to infection, significantly reduced NBV replication in PaKiT03 cells. Moreover, inhibiting IFN signalling (through specific siRNAs) increased NBV replication in L929 cells. In line with the significant cytopathic effects seen in PaKiT03 cells, we also observed a down-regulation of genes involved in cell-cell junctions, which may be related to the fusogenic effects of NBV. CONCLUSIONS: This study provides new multi-dimensional insights into the host response of mammalian cells to NBV infection. We show that IFN activity is capable of reducing NBV replication, although it is unlikely that this is solely responsible for the reduced replication of NBV in L929 cells. The molecular events that underpin the fusogenic cytopathic effects described here will prove valuable for identifying potential therapeutic targets against fusogenic orthoreovirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3994-x) contains supplementary material, which is available to authorized users.",2017 Aug 14,"['Mok, Lawrence', 'Wynne, James W.', 'Tachedjian, Mary', 'Shiell, Brian', 'Ford, Kris', 'Matthews, David A.', 'Bacic, Antony', 'Michalski, Wojtek P.']",BMC Genomics,,,False
bf78c49c0e8c888ffd4b8f800895263eeca69ae8,PMC,Proteomics informed by transcriptomics for characterising differential cellular susceptibility to Nelson Bay orthoreovirus infection,http://dx.doi.org/10.1186/s12864-017-3994-x,PMC5556373,28806913,CC BY,"BACKGROUND: Nelson Bay orthoreovirus (NBV) is a fusogenic bat borne virus with an unknown zoonotic potential. Previous studies have shown that NBV can infect and replicate in a wide variety of cell types derived from their natural host (bat), as well as from human, mouse and monkey. Within permissive cells, NBV induced significant cytopathic effects characterised by cell-cell fusion and syncytia formation. To understand the molecular events that underpin NBV infection we examined the host transcriptome and proteome response of two cell types, derived from bat (PaKiT03) and mouse (L929), to characterise differential cellular susceptibility to NBV. RESULTS: Despite significant differences in NBV replication and cytopathic effects in the L929 and PaKiT03 cells, the host response was remarkably similar in these cells. At both the transcriptome and proteome level, the host response was dominated by IFN production and signalling pathways. The majority of proteins up-regulated in L929 and PaKiT03 cells were also up-regulated at the mRNA (gene) level, and included many important IFN stimulated genes. Further functional experimentation demonstrated that stimulating IFN signalling prior to infection, significantly reduced NBV replication in PaKiT03 cells. Moreover, inhibiting IFN signalling (through specific siRNAs) increased NBV replication in L929 cells. In line with the significant cytopathic effects seen in PaKiT03 cells, we also observed a down-regulation of genes involved in cell-cell junctions, which may be related to the fusogenic effects of NBV. CONCLUSIONS: This study provides new multi-dimensional insights into the host response of mammalian cells to NBV infection. We show that IFN activity is capable of reducing NBV replication, although it is unlikely that this is solely responsible for the reduced replication of NBV in L929 cells. The molecular events that underpin the fusogenic cytopathic effects described here will prove valuable for identifying potential therapeutic targets against fusogenic orthoreovirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3994-x) contains supplementary material, which is available to authorized users.",2017 Aug 14,"['Mok, Lawrence', 'Wynne, James W.', 'Tachedjian, Mary', 'Shiell, Brian', 'Ford, Kris', 'Matthews, David A.', 'Bacic, Antony', 'Michalski, Wojtek P.']",BMC Genomics,,,True
6cc5fe5c208412e13970cc93efbd1e68d1fe6459,PMC,"Quantitative detection of human Malawi polyomavirus in nasopharyngeal aspirates, sera, and feces in Beijing, China, using real-time TaqMan-based PCR",http://dx.doi.org/10.1186/s12985-017-0817-2,PMC5557062,28806976,CC BY,"BACKGROUND: Human Malawi polyomavirus (MWPyV) was discovered in 2012, but its prevalence and clinical characteristics are largely unknown. METHODS: We used real-time TaqMan-based PCR to detect MWPyV in the feces (n = 174) of children with diarrhea, nasopharyngeal aspirates (n = 887) from children with respiratory infections, and sera (n = 200) from healthy adults, and analyzed its clinical characteristics statistically. All the MWPyV-positive specimens were also screened for other common respiratory viruses. RESULTS: Sixteen specimens were positive for MWPyV, including 13 (1.47%) respiratory samples and three (1.7%) fecal samples. The samples were all co-infected with other respiratory viruses, most commonly with influenza viruses (69.2%) and human coronaviruses (30.7%). The MWPyV-positive children were diagnosed with bronchopneumonia or viral diarrhea. They ranged in age from 12 days to 9 years, and the most frequent symptoms were cough and fever. CONCLUSIONS: Real-time PCR is an effective tool for the detection of MWPyV in different types of samples. MWPyV infection mainly occurs in young children, and fecal–oral transmission is a possible route of its transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-017-0817-2) contains supplementary material, which is available to authorized users.",2017 Aug 14,"['Ma, Fen-lian', 'Li, Dan-di', 'Wei, Tian-li', 'Li, Jin-song', 'Zheng, Li-shu']",Virol J,,,True
c9e87f843b3cf7dc47881fa3d3ccb4693d7d9521,PMC,Children are not little adults: blood transfusion in children with burn injury,http://dx.doi.org/10.1186/s41038-017-0090-z,PMC5557478,28815186,CC BY,"Blood transfusion in burns larger than 20% total body surface area (TBSA) are frequent due to operative procedures, blood sampling, and physiologic response to burn injury. Optimizing the use of blood transfusions requires an understanding of the physiology of burn injury, the risks and benefits of blood transfusion, and the indications for transfusion. Age also plays a role in determining blood transfusion requirements. Children in particular have a different physiology than adults, which needs to be considered prior to transfusing blood and blood products. This article describes the physiologic differences between children and adults in general and after burn injury and describes how these differences impact blood transfusion practices in children.",2017 Aug 15,"Palmieri, Tina L.",Burns Trauma,,,True
fd9c2af38cd8dd7a06b25e2cd2233a74a48a37cd,PMC,Rapid and sensitive detection of canine distemper virus by real-time reverse transcription recombinase polymerase amplification,http://dx.doi.org/10.1186/s12917-017-1180-7,PMC5558738,28810858,CC BY,"BACKGROUND: Canine distemper, caused by Canine distemper virus (CDV), is a highly contagious and fatal systemic disease in free-living and captive carnivores worldwide. Recombinase polymerase amplification (RPA), as an isothermal gene amplification technique, has been explored for the molecular detection of diverse pathogens. METHODS: A real-time reverse transcription RPA (RT-RPA) assay for the detection of canine distemper virus (CDV) using primers and exo probe targeting the CDV nucleocapsid protein gene was developed. A series of other viruses were tested by the RT-RPA.Thirty-two field samples were further tested by RT-RPA, and the resuts were compared with those obtained by the real-time RT-PCR. RESULTS: The RT-RPA assay was performed successfully at 40 °C, and the results were obtained within 3 min–12 min. The assay could detect CDV, but did not show cross-detection of canine parvovirus-2 (CPV-2), canine coronavirus (CCoV), canine parainfluenza virus (CPIV), pseudorabies virus (PRV) or Newcastle disease virus (NDV), demonstrating high specificity. The analytical sensitivity of RT-RPA was 31.8 copies in vitro transcribed CDV RNA, which is 10 times lower than the real-time RT-PCR. The assay performance was validated by testing 32 field samples and compared to real-time RT-PCR. The results indicated an excellent correlation between RT-RPA and a reference real-time RT-PCR method. Both assays provided the same results, and R(2) value of the positive results was 0.947. CONCLUSIONS: The results demonstrated that the RT-RPA assay offers an alternative tool for simple, rapid, and reliable detection of CDV both in the laboratory and point-of-care facility, especially in the resource-limited settings.",2017 Aug 15,"['Wang, Jianchang', 'Wang, Jinfeng', 'Li, Ruiwen', 'Liu, Libing', 'Yuan, Wanzhe']",BMC Vet Res,,,True
959b3431d24276e1b5d1bcfa7885979a4310bd98,PMC,Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo,http://dx.doi.org/10.1128/mBio.00819-17,PMC5559630,28811340,CC BY,"Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β) signaling and type II interferon (IFN-γ) signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ) integrates into this antiviral system. Here, we report that while wild-type (WT) and IFN-λ receptor knockout (λR(−/−)) mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR(−/−)) mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB). α/βR(−/−) λR(−/−) mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity.",2017 Aug 15,"['Douam, Florian', 'Soto Albrecht, Yentli E.', 'Hrebikova, Gabriela', 'Sadimin, Evita', 'Davidson, Christian', 'Kotenko, Sergei V.', 'Ploss, Alexander']",mBio,,,True
8badcfcd8aba68dceea84099e3d0f733e050109f,PMC,"Detection and genetic characterization of canine astroviruses in pet dogs in Guangxi, China",http://dx.doi.org/10.1186/s12985-017-0823-4,PMC5559842,28814340,CC BY,"BACKGROUND: Astroviruses (AstVs) have been reported to infect and cause gastroenteritis in most animal species. Human AstVs were regarded the causative agent of viral diarrhea in children. In dogs, little is known about the epidemiology and clinical significance of AstV infection. FINDINGS: In this study, we collected and tested 253 rectal swabs from pet dogs; of which 64 samples (25.3%) tested positive for AstVs with diarrhea and 15 more samples (5.9%) also was identified as AstVs, however without any clinical signs. Phylogenetic analysis of 39 partial ORF1b sequences from these samples revealed that they are similar to AstVs, which can be subdivided into three lineages. Interestingly, out of the 39 isolates sequenced, 16 isolates are shown to be in the Mamastrovirus 5/canine astrovirus (CAstV) lineage and the remaining 23 isolates displayed higher similarities with known porcine astrovirus (PoAstV) 5 and 2. Further, analysis of 13 capsid sequences from these isolates showed that they are closely clustered with Chinese or Italy CAstV isolates. CONCLUSIONS: The findings indicate that CAstVs commonly circulate in pet dogs, and our sequencing results have shown the genomic diversity of CAstVs leading to increasing number of clusters.",2017 Aug 17,"['Zhou, Huabo', 'Liu, Lin', 'Li, Ruikai', 'Qin, Yifeng', 'Fang, Qingli', 'Balasubramaniam, Vinod RMT', 'Wang, Guojun', 'Wei, Zuzhang', 'Ouyang, Kang', 'Huang, Weijian', 'Chen, Ying']",Virol J,,,True
d83954775a8f0d595494ce00018ae409739f1062,PMC,The Role of Defensins in HIV Pathogenesis,http://dx.doi.org/10.1155/2017/5186904,PMC5559915,28839349,CC BY,"Profound loss of CD4(+) T cells, progressive impairment of the immune system, inflammation, and sustained immune activation are the characteristics of human immunodeficiency virus-1 (HIV-1) infection. Innate immune responses respond immediately from the day of HIV infection, and a thorough understanding of the interaction between several innate immune cells and HIV-1 is essential to determine to what extent those cells play a crucial role in controlling HIV-1 in vivo. Defensins, divided into the three subfamilies α-, β-, and θ-defensins based on structure and disulfide linkages, comprise a critical component of the innate immune response and exhibit anti-HIV-1 activities and immunomodulatory capabilities. In humans, only α- and β-defensins are expressed in various tissues and have broad impacts on HIV-1 transmission, replication, and disease progression. θ-defensins have been identified as functional peptides in Old World monkeys, but not in humans. Instead, θ-defensins exist only as pseudogenes in humans, chimpanzees, and gorillas. The use of the synthetic θ-defensin peptide “retrocyclin” as an antiviral therapy was shown to be promising, and further research into the development of defensin-based HIV-1 therapeutics is needed. This review focuses on the role of defensins in HIV-1 pathogenesis and highlights future research efforts that warrant investigation.",2017 Aug 3,"['Pace, Barcley T.', 'Lackner, Andrew A.', 'Porter, Edith', 'Pahar, Bapi']",Mediators Inflamm,,,True
9308bade43d5c1b62c7807790327d26ccffc684d,PMC,Delta inulin-based adjuvants promote the generation of polyfunctional CD4(+) T cell responses and protection against Mycobacterium tuberculosis infection,http://dx.doi.org/10.1038/s41598-017-09119-y,PMC5561132,28819247,CC BY,"There is an urgent need for the rational design of safe and effective vaccines to protect against chronic bacterial pathogens such as Mycobacterium tuberculosis. Advax™ is a novel adjuvant based on delta inulin microparticles that enhances immunity with a minimal inflammatory profile and has entered human trials to protect against viral pathogens. In this report we determined if Advax displays broad applicability against important human pathogens by assessing protective immunity against infection with M. tuberculosis. The fusion protein CysVac2, comprising the M. tuberculosis antigens Ag85B (Rv1886c) and CysD (Rv1285) formulated with Advax provided significant protection in the lungs of M. tuberculosis-infected mice. Protection was associated with the generation of CysVac2-specific multifunctional CD4(+) T cells (IFN-γ(+)TNF(+)IL-2(+)). Addition to Advax of the TLR9 agonist, CpG oligonucleotide (Advax(CpG)), improved both the immunogenicity and protective efficacy of CysVac2. Immunisation with CysVac2/Advax(CpG) resulted in heightened release of the chemoattractants, CXCL1, CCL3, and TNF, and rapid influx of monocytes and neutrophils to the site of vaccination, with pronounced early priming of CysVac2-specific CD4(+) T cells. As delta inulin adjuvants have shown an excellent safety and tolerability profile in humans, CysVac2/Advax(CpG) is a strong candidate for further preclinical evaluation for progression to human trials.",2017 Aug 17,"['Counoupas, Claudio', 'Pinto, Rachel', 'Nagalingam, Gayathri', 'Britton, Warwick J.', 'Petrovsky, Nikolai', 'Triccas, James A.']",Sci Rep,,,False
34277d7f5f84c871e13853e830eb07b2186f8fec,PMC,Delta inulin-based adjuvants promote the generation of polyfunctional CD4(+) T cell responses and protection against Mycobacterium tuberculosis infection,http://dx.doi.org/10.1038/s41598-017-09119-y,PMC5561132,28819247,CC BY,"There is an urgent need for the rational design of safe and effective vaccines to protect against chronic bacterial pathogens such as Mycobacterium tuberculosis. Advax™ is a novel adjuvant based on delta inulin microparticles that enhances immunity with a minimal inflammatory profile and has entered human trials to protect against viral pathogens. In this report we determined if Advax displays broad applicability against important human pathogens by assessing protective immunity against infection with M. tuberculosis. The fusion protein CysVac2, comprising the M. tuberculosis antigens Ag85B (Rv1886c) and CysD (Rv1285) formulated with Advax provided significant protection in the lungs of M. tuberculosis-infected mice. Protection was associated with the generation of CysVac2-specific multifunctional CD4(+) T cells (IFN-γ(+)TNF(+)IL-2(+)). Addition to Advax of the TLR9 agonist, CpG oligonucleotide (Advax(CpG)), improved both the immunogenicity and protective efficacy of CysVac2. Immunisation with CysVac2/Advax(CpG) resulted in heightened release of the chemoattractants, CXCL1, CCL3, and TNF, and rapid influx of monocytes and neutrophils to the site of vaccination, with pronounced early priming of CysVac2-specific CD4(+) T cells. As delta inulin adjuvants have shown an excellent safety and tolerability profile in humans, CysVac2/Advax(CpG) is a strong candidate for further preclinical evaluation for progression to human trials.",2017 Aug 17,"['Counoupas, Claudio', 'Pinto, Rachel', 'Nagalingam, Gayathri', 'Britton, Warwick J.', 'Petrovsky, Nikolai', 'Triccas, James A.']",Sci Rep,,,True
be3418bd9248e2557dc8e56a51fff4b510e84b77,PMC,"Modified Vaccinia Virus Ankara Preferentially Targets Antigen Presenting Cells In Vitro, Ex Vivo and In Vivo",http://dx.doi.org/10.1038/s41598-017-08719-y,PMC5561217,28819261,CC BY,"Modified Vaccinia virus Ankara (MVA) is a promising vaccine vector with an excellent safety profile. However, despite extensive pre-clinical and clinical testing, surprisingly little is known about the cellular tropism of MVA, especially in relevant animal species. Here, we performed in vitro, ex vivo and in vivo experiments with recombinant MVA expressing green fluorescent protein (rMVA-GFP). In both human peripheral blood mononuclear cells and mouse lung explants, rMVA-GFP predominantly infected antigen presenting cells. Subsequent in vivo experiments performed in mice, ferrets and non-human primates indicated that preferential targeting of dendritic cells and alveolar macrophages was observed after respiratory administration, although subtle differences were observed between the respective animal species. Following intramuscular injection, rMVA-GFP was detected in interdigitating cells between myocytes, but also in myocytes themselves. These data are important in advancing our understanding of the basis for the immunogenicity of MVA-based vaccines and aid rational vaccine design and delivery strategies.",2017 Aug 17,"['Altenburg, Arwen F.', 'van de Sandt, Carolien E.', 'Li, Bobby W. S.', 'MacLoughlin, Ronan J.', 'Fouchier, Ron A. M.', 'van Amerongen, Geert', 'Volz, Asisa', 'Hendriks, Rudi W.', 'de Swart, Rik L.', 'Sutter, Gerd', 'Rimmelzwaan, Guus F.', 'de Vries, Rory D.']",Sci Rep,,,False
9eb3ea6224aabe868a10af37dc829b9636be5856,PMC,"Modified Vaccinia Virus Ankara Preferentially Targets Antigen Presenting Cells In Vitro, Ex Vivo and In Vivo",http://dx.doi.org/10.1038/s41598-017-08719-y,PMC5561217,28819261,CC BY,"Modified Vaccinia virus Ankara (MVA) is a promising vaccine vector with an excellent safety profile. However, despite extensive pre-clinical and clinical testing, surprisingly little is known about the cellular tropism of MVA, especially in relevant animal species. Here, we performed in vitro, ex vivo and in vivo experiments with recombinant MVA expressing green fluorescent protein (rMVA-GFP). In both human peripheral blood mononuclear cells and mouse lung explants, rMVA-GFP predominantly infected antigen presenting cells. Subsequent in vivo experiments performed in mice, ferrets and non-human primates indicated that preferential targeting of dendritic cells and alveolar macrophages was observed after respiratory administration, although subtle differences were observed between the respective animal species. Following intramuscular injection, rMVA-GFP was detected in interdigitating cells between myocytes, but also in myocytes themselves. These data are important in advancing our understanding of the basis for the immunogenicity of MVA-based vaccines and aid rational vaccine design and delivery strategies.",2017 Aug 17,"['Altenburg, Arwen F.', 'van de Sandt, Carolien E.', 'Li, Bobby W. S.', 'MacLoughlin, Ronan J.', 'Fouchier, Ron A. M.', 'van Amerongen, Geert', 'Volz, Asisa', 'Hendriks, Rudi W.', 'de Swart, Rik L.', 'Sutter, Gerd', 'Rimmelzwaan, Guus F.', 'de Vries, Rory D.']",Sci Rep,,,True
0a789bc7f1713d549288d3effb72ff34cd3b0ab0,PMC,Respiratory syncytial virus (RSV) entry is inhibited by serine protease inhibitor AEBSF when present during an early stage of infection,http://dx.doi.org/10.1186/s12985-017-0824-3,PMC5561636,28818113,CC BY,"BACKGROUND: Host proteases have been shown to play important roles in many viral activities such as entry, uncoating, viral protein production and disease induction. Therefore, these cellular proteases are putative targets for the development of antivirals that inhibit their activity. Host proteases have been described to play essential roles in Ebola, HCV, HIV and influenza, such that specific protease inhibitors are able to reduce infection. RSV utilizes a host protease in its replication cycle but its potential as antiviral target is unknown. Therefore, we evaluated the effect of protease inhibitors on RSV infection. METHODS: To measure the sensitivity of RSV infection to protease inhibitors, cells were infected with RSV and incubated for 18 h in the presence or absence of the inhibitors. Cells were fixed, stained and studied using fluorescence microscopy. RESULTS: Several protease inhibitors, representing different classes of proteases (AEBSF, Pepstatin A, E-64, TPCK, PMSF and aprotinin), were tested for inhibitory effects on an RSV A2 infection of HEp-2 cells. Different treatment durations, ranging from 1 h prior to inoculation and continuing for 18 h during the assay, were evaluated. Of all the inhibitors tested, AEBSF and TPCK significantly decreased RSV infection. To ascertain that the observed effect of AEBSF was not a specific feature related to HEp-2 cells, A549 and BEAS-2B cells were also used. Similar to HEp-2, an almost complete block in the number of RSV infected cells after 18 h of incubation was observed and the effect was dose-dependent. To gain insight into the mechanism of this inhibition, AEBSF treatment was applied during different phases of an infection cycle (pre-, peri- and post-inoculation treatment). The results from these experiments indicate that AEBSF is mainly active during the early entry phase of RSV. The inhibitory effect was also observed with other RSV isolates A1998/3–2 and A2000/3–4, suggesting that this is a general feature of RSV. CONCLUSION: RSV infection can be inhibited by broad serine protease inhibitors, AEBSF and TPCK. We confirmed that AEBSF inhibition is independent of the cell line used or RSV strain. The time point at which treatment with the inhibitor was most potent, was found to coincide with the expected moment of entry of the virion with the host cell.",2017 Aug 17,"['Van der Gucht, Winke', 'Leemans, Annelies', 'De Schryver, Marjorie', 'Heykers, Annick', 'Caljon, Guy', 'Maes, Louis', 'Cos, Paul', 'Delputte, Peter L.']",Virol J,,,True
dbd27297be0609a02729bd99ac744b997d9e647f,PMC,Egyptian rousette bats maintain long-term protective immunity against Marburg virus infection despite diminished antibody levels,http://dx.doi.org/10.1038/s41598-017-07824-2,PMC5562751,28821722,CC BY,"Although bats are natural reservoir hosts for numerous zoonotic viruses, little is known about the long-term dynamics of the host immune response following infection and how these viruses are maintained in nature. The Egyptian rousette bat (ERB) is a known reservoir host for Marburg virus (MARV). Following infection of ERBs with MARV, virus-specific IgG antibodies are induced but rapidly wane and by 3 months post-infection the bats are seronegative. To determine whether reinfection of ERBs plays a role in MARV maintenance, we challenge groups of ERBs that were “naturally” or experimentally infected with MARV 17–24 months prior. No bats in either group exhibit evidence of MARV replication or shedding and all bats develop virus-specific secondary immune responses. This study demonstrates that infection of ERBs with MARV induces long-term protective immunity against reinfection and indicates that other factors, such as host population dynamics, drive MARV maintenance in nature.",2017 Aug 18,"['Schuh, Amy J.', 'Amman, Brian R.', 'Sealy, Tara K.', 'Spengler, Jessica R.', 'Nichol, Stuart T.', 'Towner, Jonathan S.']",Sci Rep,,,True
e1be06ec4d2cc4190334ac135f85090e6d3f380f,PMC,"Using the Kulldorff’s scan statistical analysis to detect spatio-temporal clusters of tuberculosis in Qinghai Province, China, 2009–2016",http://dx.doi.org/10.1186/s12879-017-2643-y,PMC5563899,28826399,CC BY,"BACKGROUND: Although the incidence of tuberculosis (TB) in most parts of China are well under control now, in less developed areas such as Qinghai, TB still remains a major public health problem. This study aims to reveal the spatio-temporal patterns of TB in the Qinghai province, which could be helpful in the planning and implementing key preventative measures. METHODS: We extracted data of reported TB cases in the Qinghai province from the China Information System for Disease Control and Prevention (CISDCP) during January 2009 to December 2016. The Kulldorff’s retrospective space-time scan statistics, calculated by using the discrete Poisson probability model, was used to identify the temporal, spatial, and spatio-temporal clusters of TB at the county level in Qinghai. RESULTS: A total of 48,274 TB cases were reported from 2009 to 2016 in Qinghai. Results of the Kulldorff’s scan revealed that the TB cases in Qinghai were significantly clustered in spatial, temporal, and spatio-temporal distribution. The most likely spatio-temporal cluster (LLR = 2547.64, RR = 4.21, P < 0.001) was mainly concentrated in the southwest of Qinghai, covering seven counties and clustered in the time frame from September 2014 to December 2016. CONCLUSION: This study identified eight significant space-time clusters of TB in Qinghai from 2009 to 2016, which could be helpful in prioritizing resource assignment in high-risk areas for TB control and elimination in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-017-2643-y) contains supplementary material, which is available to authorized users.",2017 Aug 21,"['Rao, Huaxiang', 'Shi, Xinyu', 'Zhang, Xi']",BMC Infect Dis,,,True
c60b9bd1c5edac3f1f4916571a10a6daf9b569a6,PMC,Kangfuxinye Enema Combined with Mesalamine for Ulcerative Colitis: A Systematic Review and GRADE Approach,http://dx.doi.org/10.1155/2017/6019530,PMC5564127,28848616,CC BY,"OBJECTIVES: To critically appraise the efficacy and safety of Kangfuxinye enema combined with mesalamine for the ulcerative colitis (UC) patients and in addition to grade the quality of evidence by using the GRADE (grading of recommendations, assessment, development, and evaluation) approach. METHODS: A literature search was performed in the Cochrane Library, MEDLINE, EMBASE, CBM, CNKI, VIP, and WanFang Databases. The search restrictions were patients with UC and RCTs. Studies including other treatments except Kangfuxinye with mesalamine were excluded. RESULTS: Nineteen studies met the inclusion criteria. We found significant benefits of Kangfuxinye combined with mesalamine against mesalamine alone in improving response rate as well as reducing the recurrence rate and inflammation rate; meanwhile, the increase of the adverse events rate was not observed. Furthermore, the symptoms remission rate and the cure time were insignificant statistically. Additionally, GRADE results indicated that the quality of evidence regarding the above 6 outcomes was rated from very low to moderate quality. CONCLUSIONS: Although Kangfuxinye enema seems effective and safe for treating UC patients in this systematic review, Kangfuxinye enema combined with mesalamine was weakly recommended due to very low to moderate quality of available evidence by the GRADE approach.",2017 Aug 7,"['Ren, Peng-wei', 'Yang, Wen-jie', 'Wang, Dan-dan', 'Shan, Jing-yan', 'Kang, De-ying', 'Hong, Qi', 'Wen, Shu', 'Zhang, Ru-wen']",Evid Based Complement Alternat Med,,,True
9b8a2314912eaeb1c509cf88492f463148a0a9ed,PMC,The nucleocapsid proteins of mouse hepatitis virus and severe acute respiratory syndrome coronavirus share the same IFN-β antagonizing mechanism: attenuation of PACT-mediated RIG-I/MDA5 activation,http://dx.doi.org/10.18632/oncotarget.17912,PMC5564796,28591694,CC BY,"Coronaviruses (CoVs) are a huge threat to both humans and animals and have evolved elaborate mechanisms to antagonize interferons (IFNs). Nucleocapsid (N) protein is the most abundant viral protein in CoV-infected cells, and has been identified as an innate immunity antagonist in several CoVs, including mouse hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV. However, the underlying molecular mechanism(s) remain unclear. In this study, we found that MHV N protein inhibited Sendai virus and poly(I:C)-induced IFN-β production by targeting a molecule upstream of retinoic acid-induced gene I (RIG-I) and melanoma differentiation gene 5 (MDA5). Further studies showed that both MHV and SARS-CoV N proteins directly interacted with protein activator of protein kinase R (PACT), a cellular dsRNA-binding protein that can bind to RIG-I and MDA5 to activate IFN production. The N–PACT interaction sequestered the association of PACT and RIG-I/MDA5, which in turn inhibited IFN-β production. However, the N proteins from porcine epidemic diarrhea virus (PEDV) and porcine reproductive and respiratory syndrome virus (PRRSV), which are also classified in the order Nidovirales, did not interact and counteract with PACT. Taken together, our present study confirms that both MHV and SARS-CoV N proteins can perturb the function of cellular PACT to circumvent the innate antiviral response. However, this strategy does not appear to be used by all CoVs N proteins.",2017 May 17,"['Ding, Zhen', 'Fang, Liurong', 'Yuan, Shuangling', 'Zhao, Ling', 'Wang, Xunlei', 'Long, Siwen', 'Wang, Mohan', 'Wang, Dang', 'Foda, Mohamed Frahat', 'Xiao, Shaobo']",Oncotarget,,,True
e55df621c9df11f9127cdb8829686868bd2ec1cc,PMC,Antimicrobial activity of bovine NK-lysin-derived peptides on bovine respiratory pathogen Histophilus somni,http://dx.doi.org/10.1371/journal.pone.0183610,PMC5565109,28827826,CC0,"Bovine NK-lysins, which are functionally and structurally similar to human granulysin and porcine NK-lysin, are predominantly found in the granules of cytotoxic T-lymphocytes and NK-cells. Although antimicrobial activity of bovine NK-lysin has been assessed for several bacterial pathogens, not all the important bacterial pathogens that are involved in the bovine respiratory disease complex have been studied. Therefore the objective of the present study was to evaluate the antimicrobial activity of bovine NK-lysin-derived peptides on bovine respiratory pathogen Histophilus somni. Four, 30-mer peptides corresponding to the functional region of NK-lysin helices 2 and 3 were synthesized and assessed for antibacterial activity on four bovine pneumonic H. somni isolates. Although there were some differences in the efficiency of bactericidal activity among the NK-lysin peptides at lower concentrations (2–5 μM), all four peptides effectively killed most H. somni isolates at higher concentrations (10–30 μM) as determined by a bacterial killing assay. Confocal microscopic and flow cytometric analysis of Live/Dead Baclight stained H. somni (which were preincubated with NK-lysin peptides) were consistent with the killing assay findings and suggest NK-lysin peptides are bactericidal for H. somni. Among the four peptides, NK2A-derived peptide consistently showed the highest antimicrobial activity against all four H. somni isolates. Electron microscopic examination of H. somni following incubation with NK-lysin revealed extensive cell membrane damage, protrusions of outer membranes, and cytoplasmic content leakage. Taken together, the findings from this study clearly demonstrate the antimicrobial activity of all four bovine NK-lysin-derived peptides against bovine H. somni isolates.",2017 Aug 21,"['Dassanayake, Rohana P.', 'Falkenberg, Shollie M.', 'Briggs, Robert E.', 'Tatum, Fred M.', 'Sacco, Randy E.']",PLoS One,,,True
b313d134237c1d12ea832bcad736937d908a6c25,PMC,MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis,http://dx.doi.org/10.1128/mBio.00665-17,PMC5565963,28830941,CC BY,"While dispensable for viral replication, coronavirus (CoV) accessory open reading frame (ORF) proteins often play critical roles during infection and pathogenesis. Utilizing a previously generated mutant, we demonstrate that the absence of all four Middle East respiratory syndrome CoV (MERS-CoV) accessory ORFs (deletion of ORF3, -4a, -4b, and -5 [dORF3-5]) has major implications for viral replication and pathogenesis. Importantly, attenuation of the dORF3-5 mutant is primarily driven by dysregulated host responses, including disrupted cell processes, augmented interferon (IFN) pathway activation, and robust inflammation. In vitro replication attenuation also extends to in vivo models, allowing use of dORF3-5 as a live attenuated vaccine platform. Finally, examination of ORF5 implicates a partial role in modulation of NF-κB-mediated inflammation. Together, the results demonstrate the importance of MERS-CoV accessory ORFs for pathogenesis and highlight them as potential targets for surveillance and therapeutic treatments moving forward.",2017 Aug 22,"['Menachery, Vineet D.', 'Mitchell, Hugh D.', 'Cockrell, Adam S.', 'Gralinski, Lisa E.', 'Yount, Boyd L.', 'Graham, Rachel L.', 'McAnarney, Eileen T.', 'Douglas, Madeline G.', 'Scobey, Trevor', 'Beall, Anne', 'Dinnon, Kenneth', 'Kocher, Jacob F.', 'Hale, Andrew E.', 'Stratton, Kelly G.', 'Waters, Katrina M.', 'Baric, Ralph S.']",mBio,,,True
9e881f35d3222748d7c2cb9a2a8b9b0d99246564,PMC,Immortalization and Characterization of Porcine Macrophages That Had Been Transduced with Lentiviral Vectors Encoding the SV40 Large T Antigen and Porcine Telomerase Reverse Transcriptase,http://dx.doi.org/10.3389/fvets.2017.00132,PMC5566601,28871285,CC BY,"The domestic pig is an important agricultural animal, and thus, infectious diseases that affect pigs can cause severe economic losses in the global swine industry. Various porcine pathogens target macrophages, which are classical innate immune cells. Although macrophages basically protect the host from pathogens, they also seem to contribute to infectious processes. Therefore, cultured macrophages can be used to develop in vitro models for studying not only genes associated with porcine innate immunity but also the infectious processes of porcine pathogens. However, the availability of porcine macrophage cell lines is limited. In this study, we describe a novel immortalized porcine kidney-derived macrophage (IPKM) cell line, which was generated by transferring the SV40 large T antigen (SV40LT) and porcine telomerase reverse transcriptase (pTERT) genes into primary porcine kidney-derived macrophages using lentiviral vectors. The IPKM displayed a typical macrophage morphology and was routinely passaged (doubling time: about 4 days). These cells were immunostained for macrophage markers. In addition, they exhibited substantial phagocytosis of polystyrene microbeads and released inflammatory cytokines upon lipopolysaccharide (LPS) stimulation. Furthermore, the maturation and secretion of interleukin-1β were observed after nigericin-induced inflammasome activation in LPS-primed IPKM. These findings suggest that IPKM exhibit the typical inflammatory characteristics of macrophages. By transferring the SV40LT and pTERT genes using lentiviral vectors, we also successfully immortalized macrophages derived from the peripheral blood of a low-density lipoprotein receptor-deficient pig. These results suggest that the co-expression of SV40LT and pTERT is an effective way of immortalizing porcine macrophages.",2017 Aug 21,"['Takenouchi, Takato', 'Kitani, Hiroshi', 'Suzuki, Shunichi', 'Nakai, Michiko', 'Fuchimoto, Dai-ichiro', 'Tsukimoto, Mitsutoshi', 'Shinkai, Hiroki', 'Sato, Mitsuru', 'Uenishi, Hirohide']",Front Vet Sci,,,True
f60130a29e062ba506c8fd018dad0da86557380a,PMC,Phellodendron chinense Schneid: A novel yellow-emitting luminescent material for white light-emitting diodes,http://dx.doi.org/10.1038/s41598-017-09291-1,PMC5567165,28827629,CC BY,"To facilitate the next generation of environmental material for white light emitting diodes, the discovery of natural luminesce is essential. In this study, we disclose a rare-earth free and yellow-emission phosphor, Phellodendron, which could be both excited by near ultraviolet light and blue light. The new yellow phosphor is obtained by extraction of Phellodendron chinense Schneid. The emission wavelength, full width at half maximum and CIE coordinates of extracted Phellodendron are 540 nm, 120 nm and (0.41, 0.55), respectively. The corresponding luminescent properties of Phellodendron are characterized by PL, PLE, reflection spectra, FITR and decay lifetime. Surprising thing is luminous intensity of Phellodendron phosphors excited at 380 nm was stronger than YAG:Ce phosphor by more than 139%. In addition, we firstly introduce the yellow phosphor in white LED fabrication by combining blue chip and Y(3)Al(5)O(12):Ce(3+) phosphor, to create warm white. For comparison, red-emission CaAlSiN(3):Eu(2+) phosphors are also introduced for LED package tests. The results demonstrate that Phellodendron is a potential candidate for white LED applications.",2017 Aug 21,"['Lin, Pin-Chun', 'Hsu, Kuei-Ting', 'Shiu, Ming-Hsiu', 'Liu, Wei-Ren']",Sci Rep,,,False
9740b9f6f49dc554d7be515871bd31123bda5473,PMC,Phellodendron chinense Schneid: A novel yellow-emitting luminescent material for white light-emitting diodes,http://dx.doi.org/10.1038/s41598-017-09291-1,PMC5567165,28827629,CC BY,"To facilitate the next generation of environmental material for white light emitting diodes, the discovery of natural luminesce is essential. In this study, we disclose a rare-earth free and yellow-emission phosphor, Phellodendron, which could be both excited by near ultraviolet light and blue light. The new yellow phosphor is obtained by extraction of Phellodendron chinense Schneid. The emission wavelength, full width at half maximum and CIE coordinates of extracted Phellodendron are 540 nm, 120 nm and (0.41, 0.55), respectively. The corresponding luminescent properties of Phellodendron are characterized by PL, PLE, reflection spectra, FITR and decay lifetime. Surprising thing is luminous intensity of Phellodendron phosphors excited at 380 nm was stronger than YAG:Ce phosphor by more than 139%. In addition, we firstly introduce the yellow phosphor in white LED fabrication by combining blue chip and Y(3)Al(5)O(12):Ce(3+) phosphor, to create warm white. For comparison, red-emission CaAlSiN(3):Eu(2+) phosphors are also introduced for LED package tests. The results demonstrate that Phellodendron is a potential candidate for white LED applications.",2017 Aug 21,"['Lin, Pin-Chun', 'Hsu, Kuei-Ting', 'Shiu, Ming-Hsiu', 'Liu, Wei-Ren']",Sci Rep,,,True
9439183d2e5253d1641a64c775dbc17767b01690,PMC,Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection,http://dx.doi.org/10.1038/s41598-017-09536-z,PMC5567209,28831119,CC BY,"Severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-like coronavirus are a potential threat to global health. However, reviews of the long-term effects of clinical treatments in SARS patients are lacking. Here a total of 25 recovered SARS patients were recruited 12 years after infection. Clinical questionnaire responses and examination findings indicated that the patients had experienced various diseases, including lung susceptibility to infections, tumors, cardiovascular disorders, and abnormal glucose metabolism. As compared to healthy controls, metabolomic analyses identified significant differences in the serum metabolomes of SARS survivors. The most significant metabolic disruptions were the comprehensive increase of phosphatidylinositol and lysophospha tidylinositol levels in recovered SARS patients, which coincided with the effect of methylprednisolone administration investigated further in the steroid treated non-SARS patients with severe pneumonia. These results suggested that high-dose pulses of methylprednisolone might cause long-term systemic damage associated with serum metabolic alterations. The present study provided information for an improved understanding of coronavirus-associated pathologies, which might permit further optimization of clinical treatments.",2017 Aug 22,"['Wu, Qi', 'Zhou, Lina', 'Sun, Xin', 'Yan, Zhongfang', 'Hu, Chunxiu', 'Wu, Junping', 'Xu, Long', 'Li, Xue', 'Liu, Huiling', 'Yin, Peiyuan', 'Li, Kuan', 'Zhao, Jieyu', 'Li, Yanli', 'Wang, Xiaolin', 'Li, Yu', 'Zhang, Qiuyang', 'Xu, Guowang', 'Chen, Huaiyong']",Sci Rep,,,True
7f30c654e9e5f42fde4d09ee04d91b7f56b6b73e,PMC,One-domain CD4 Fused to Human Anti-CD16 Antibody Domain Mediates Effective Killing of HIV-1-Infected Cells,http://dx.doi.org/10.1038/s41598-017-07966-3,PMC5567353,28831040,CC BY,"Bispecific killer cells engagers (BiKEs) which can bind to natural killer (NK) cells through the activating receptor CD16A and guide them to cells expressing the HIV-1 envelope glycoprotein (Env) are a promising new weapon for elimination of infected cells and eradication of the virus. Here we report the design, generation and characterization of BiKEs which consist of CD16A binding human antibody domains fused through a flexible linker to an engineered one-domain soluble human CD4. In presence of cells expressing HIV-1 envelope glycoproteins (Envs), these BiKEs activated specifically CD16A-expressing Jurkat T cells, degranulated NK cells, induced cytokine production and killed Env-expressing cells. They also effectively mediated killing of chronically and acutely HIV-1 infected T cells by human peripheral blood mononuclear cells. The presumed ability of these CD4-based BiKEs to bind all HIV-1 isolates, their small size and fully human origin, combined with high efficacy suggest their potential for HIV-1 eradication.",2017 Aug 22,"['Li, Wei', 'Wu, Yanling', 'Kong, Desheng', 'Yang, Hongjia', 'Wang, Yanping', 'Shao, Jiping', 'Feng, Yang', 'Chen, Weizao', 'Ma, Liying', 'Ying, Tianlei', 'Dimitrov, Dimiter S.']",Sci Rep,,,False
5fbed89aaeda377c284ad02fc944fc80571e0cab,PMC,One-domain CD4 Fused to Human Anti-CD16 Antibody Domain Mediates Effective Killing of HIV-1-Infected Cells,http://dx.doi.org/10.1038/s41598-017-07966-3,PMC5567353,28831040,CC BY,"Bispecific killer cells engagers (BiKEs) which can bind to natural killer (NK) cells through the activating receptor CD16A and guide them to cells expressing the HIV-1 envelope glycoprotein (Env) are a promising new weapon for elimination of infected cells and eradication of the virus. Here we report the design, generation and characterization of BiKEs which consist of CD16A binding human antibody domains fused through a flexible linker to an engineered one-domain soluble human CD4. In presence of cells expressing HIV-1 envelope glycoproteins (Envs), these BiKEs activated specifically CD16A-expressing Jurkat T cells, degranulated NK cells, induced cytokine production and killed Env-expressing cells. They also effectively mediated killing of chronically and acutely HIV-1 infected T cells by human peripheral blood mononuclear cells. The presumed ability of these CD4-based BiKEs to bind all HIV-1 isolates, their small size and fully human origin, combined with high efficacy suggest their potential for HIV-1 eradication.",2017 Aug 22,"['Li, Wei', 'Wu, Yanling', 'Kong, Desheng', 'Yang, Hongjia', 'Wang, Yanping', 'Shao, Jiping', 'Feng, Yang', 'Chen, Weizao', 'Ma, Liying', 'Ying, Tianlei', 'Dimitrov, Dimiter S.']",Sci Rep,,,True
7657f444f3aba83bd7db9420f565557a282fe4da,PMC,A two-stage temperature control strategy enhances extracellular secretion of recombinant α-cyclodextrin glucosyltransferase in Escherichia coli,http://dx.doi.org/10.1186/s13568-017-0465-3,PMC5567581,28831769,CC BY,"The effects of temperature on extracellular secretion of the α-cyclodextrin glucosyltransferase (α-CGTase) from Paenibacillus macerans JFB05-01 by Escherichia coli were investigated. When protein expression was induced at constant temperature, the greatest amount of extracellular recombinant α-CGTase was produced at 25 °C. Higher or lower induction temperatures were not conducive to extracellular secretion of recombinant α-CGTase. To enhance extracellular secretion of α-CGTase by E. coli, a two-stage temperature control strategy was adopted. When expression was induced at 25 °C for 32 h, and then the temperature was shifted to 30 °C, the extracellular α-CGTase activity at 90 h was 45% higher than that observed when induction was performed at a constant temperature of 25 °C. Further experiments suggested that raising the induction temperature can benefit the transport of recombinant enzyme and compensate for the decreased rate of recombinant enzyme synthesis during the later stage of expression. This report provides a new method of optimizing the secretory expression of recombinant enzymes by E. coli.",2017 Aug 23,"['Li, Yang', 'Liu, Jia', 'Wang, Yinglan', 'Liu, Bingjie', 'Xie, Xiaofang', 'Jia, Rui', 'Li, Caiming', 'Li, Zhaofeng']",AMB Express,,,True
76d446112561ab0100feb5323f071191e0aa02c6,PMC,Etiology of acute respiratory disease in fattening pigs in Finland,http://dx.doi.org/10.1186/s40813-017-0065-2,PMC5568250,28852568,CC BY,"BACKGROUND: The objective of our study was to clinically and etiologically investigate acute outbreaks of respiratory disease in Finland. Our study also aimed to evaluate the clinical use of various methods in diagnosing respiratory infections under field conditions and to describe the antimicrobial resistance profile of the main bacterial pathogen(s) found during the study. METHODS: A total of 20 case herds having finishing pigs showing acute respiratory symptoms and eight control herds showing no clinical signs suggesting of respiratory problems were enrolled in the study. Researchers visited each herd twice, examining and bleeding 20 pigs per herd. In addition, nasal swab samples were taken from 20 pigs and three pigs per case herd were necropsied during the first visit. Serology was used to detect Actinobacillus pleuropneumoniae (APP), swine influenza virus (SIV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine respiratory coronavirus (PRCV) and Mycoplasma hyopneumoniae antibodies. Polymerase chain reaction (PCR) was used to investigate the presence of porcine circovirus type 2 (PCV2) in serum and SIV in the nasal and lung samples. Pathology and bacteriology, including antimicrobial resistance determination, were performed on lung samples obtained from the field necropsies. RESULTS: According to the pathology and bacteriology of the lung samples, APP and Ascaris suum were the main causes of respiratory outbreaks in 14 and three herds respectively, while the clinical signs in three other herds had a miscellaneous etiology. SIV, APP and PCV2 caused concurrent infections in certain herds but they were detected serologically or with PCR also in control herds, suggesting possible subclinical infections. APP was isolated from 16 (80%) case herds. Marked resistance was observed against tetracycline for APP, some resistance was detected against trimethoprim/sulfamethoxazole, ampicillin and penicillin, and no resistance against florfenicol, enrofloxacin, tulathromycin or tiamulin was found. Serology, even from paired serum samples, gave inconclusive results for acute APP infection diagnosis. CONCLUSIONS: APP was the most common cause for acute respiratory outbreaks in our study. SIV, A. suum, PCV2 and certain opportunistic bacteria were also detected during the outbreaks; however, viral pathogens appeared less important than bacteria. Necropsies supplemented with microbiology were the most efficient diagnostic methods in characterizing the studied outbreaks.",2017 Aug 23,"['Haimi-Hakala, Minna', 'Hälli, Outi', 'Laurila, Tapio', 'Raunio-Saarnisto, Mirja', 'Nokireki, Tiina', 'Laine, Taina', 'Nykäsenoja, Suvi', 'Pelkola, Kirsti', 'Segales, Joaquim', 'Sibila, Marina', 'Oliviero, Claudio', 'Peltoniemi, Olli', 'Pelkonen, Sinikka', 'Heinonen, Mari']",Porcine Health Manag,,,True
67a33cdb3341a7385fe74d41f0ba2b9e22f68300,PMC,"The porcine translational research database: a manually curated, genomics and proteomics-based research resource",http://dx.doi.org/10.1186/s12864-017-4009-7,PMC5568366,28830355,CC BY,"BACKGROUND: The use of swine in biomedical research has increased dramatically in the last decade. Diverse genomic- and proteomic databases have been developed to facilitate research using human and rodent models. Current porcine gene databases, however, lack the robust annotation to study pig models that are relevant to human studies and for comparative evaluation with rodent models. Furthermore, they contain a significant number of errors due to their primary reliance on machine-based annotation. To address these deficiencies, a comprehensive literature-based survey was conducted to identify certain selected genes that have demonstrated function in humans, mice or pigs. RESULTS: The process identified 13,054 candidate human, bovine, mouse or rat genes/proteins used to select potential porcine homologs by searching multiple online sources of porcine gene information. The data in the Porcine Translational Research Database ((http://www.ars.usda.gov/Services/docs.htm?docid=6065) is supported by >5800 references, and contains 65 data fields for each entry, including >9700 full length (5′ and 3′) unambiguous pig sequences, >2400 real time PCR assays and reactivity information on >1700 antibodies. It also contains gene and/or protein expression data for >2200 genes and identifies and corrects 8187 errors (gene duplications artifacts, mis-assemblies, mis-annotations, and incorrect species assignments) for 5337 porcine genes. CONCLUSIONS: This database is the largest manually curated database for any single veterinary species and is unique among porcine gene databases in regard to linking gene expression to gene function, identifying related gene pathways, and connecting data with other porcine gene databases. This database provides the first comprehensive description of three major Super-families or functionally related groups of proteins (Cluster of Differentiation (CD) Marker genes, Solute Carrier Superfamily, ATP binding Cassette Superfamily), and a comparative description of porcine microRNAs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-4009-7) contains supplementary material, which is available to authorized users.",2017 Aug 22,"['Dawson, Harry D.', 'Chen, Celine', 'Gaynor, Brady', 'Shao, Jonathan', 'Urban, Joseph F.']",BMC Genomics,,,True
41743a48f1acec724d627f76e02e85137debc076,PMC,IRAK-M alters the polarity of macrophages to facilitate the survival of Mycobacterium tuberculosis,http://dx.doi.org/10.1186/s12866-017-1095-2,PMC5569470,28835201,CC BY,"BACKGROUND: Intracellular bacterium, Mycobacterium tuberculosis (M. tb), infects specifically macrophages as host cells. IRAK-M, a member of IRAK family, is a negative regulator in TLR signaling and specifically expresses in monocytes and macrophages. The role of IRAK-M in intracellular growth of M. tb and macrophage polarization was explored, for deeply understanding the pathogenesis of M. tb, the significance of IRAK-M to innate immunity and pathogen-host interaction. METHODS: IRAK-M expression was detected in M. tb infected macrophages and in human lung tissue of pulmonary tuberculosis with immunofluorescence staining, Western blot and immunohistochemistry. IRAK-M knock-down and over-expressing cell strains were constructed and intracellular survival of M. tb was investigated by acid-fast staining and colony forming units. Molecular markers of M1-type (pSTAT1 and iNOS) and M2-type (pSTAT6 and Arg-1) macrophages were detected using Western blot in IRAK-M knockdown U937 cells infected with M. tb H37Rv. U937 cells were stimulated with immunostimulant CpG7909 into M1 status and then infected with M. tb H37Rv. Expression of IRAK-M, IRAK-4 and iNOS was detected with immunofluorescence staining and Western blot, to evaluate the effect of IRAK-M to CpG directed M1-type polarization of macrophages during M. tb infection. Molecules related with macrophage’s bactericidal ability such as Hif-1 and phosphorylated ERK1/2 were detected with immunohistochemistry and Western blot. RESULTS: IRAK-M increased in M. tb infected macrophage cells and also in human lung tissue of pulmonary tuberculosis. IRAK-M over-expression resulted in higher bacterial load, while IRAK-M interference resulted in lower bacterial load in M. tb infected cells. During M. tb infection, IRAK-M knockdown induced M1-type, while inhibited M2-type polarization of macrophage. M1-type polarization of U937 cells induced by CpG7909 was inhibited by M. tb infection, which was reversed by IRAK-M knockdown in U937 cells. IRAK-M affected Hif-1 and MAPK signaling cascade during M. tb infection. CONCLUSIONS: Conclusively, IRAK-M might alter the polarity of macrophages, to facilitate intracellular survival of M. tb and affect Th1-type immunity of the host, which is helpful to understanding the pathogenesis of M. tb.",2017 Aug 23,"['Shen, Pei', 'Li, Quan', 'Ma, Jilei', 'Tian, Maopeng', 'Hong, Fei', 'Zhai, Xinjie', 'Li, Jianrong', 'Huang, Hanju', 'Shi, Chunwei']",BMC Microbiol,,,True
ba92c1db62eab39acfe0df0cbcb766a31eb9e4f5,PMC,"Acute respiratory infections in hospitalized children in Vientiane, Lao PDR – the importance of Respiratory Syncytial Virus",http://dx.doi.org/10.1038/s41598-017-09006-6,PMC5571090,28839157,CC BY,"The Human respiratory syncytial virus (RSV) is one of the most important viral pathogens, causing epidemics of acute respiratory infection (ARI), especially bronchiolitis and pneumonia, in children worldwide. To investigate the RSV burden in Laos, we conducted a one-year study in children <5 years old admitted to Mahosot Hospital, Vientiane Capital, to describe clinical and epidemiological characteristics and predictive factors for severity of RSV-associated ARI. Pooled nasal and throat swabs were tested using multiplex real-time PCR for 33 respiratory pathogens (FTD(®) kit). A total of 383 patients were included, 277 (72.3%) of whom presented with pneumonia. 377 (98.4%) patients were positive for at least one microorganism, of which RSV was the most common virus (41.0%), with a peak observed between June and September, corresponding to the rainy season. Most RSV inpatients had pneumonia (84.1%), of whom 35% had severe pneumonia. Children <3-months old were a high-risk group for severe pneumonia, independently of RSV infection. Our study suggests that RSV infection is frequent in Laos and commonly associated with pneumonia in hospitalized young children. Further investigations are required to provide a better overall view of the Lao nationwide epidemiology and public health burden of RSV infection over time.",2017 Aug 24,"['Nguyen, Van Hoan', 'Dubot-Pérès, Audrey', 'Russell, Fiona M.', 'Dance, David A. B.', 'Vilivong, Keoudomphone', 'Phommachan, Souphatsone', 'Syladeth, Chanthaphone', 'Lai, Jana', 'Lim, Ruth', 'Morpeth, Melinda', 'Mayxay, Mayfong', 'Newton, Paul N.', 'Richet, Hervé', 'De Lamballerie, Xavier']",Sci Rep,,,False
2f2f4654524b26b1b253d2ca5a6f6bf7e7455f36,PMC,"Acute respiratory infections in hospitalized children in Vientiane, Lao PDR – the importance of Respiratory Syncytial Virus",http://dx.doi.org/10.1038/s41598-017-09006-6,PMC5571090,28839157,CC BY,"The Human respiratory syncytial virus (RSV) is one of the most important viral pathogens, causing epidemics of acute respiratory infection (ARI), especially bronchiolitis and pneumonia, in children worldwide. To investigate the RSV burden in Laos, we conducted a one-year study in children <5 years old admitted to Mahosot Hospital, Vientiane Capital, to describe clinical and epidemiological characteristics and predictive factors for severity of RSV-associated ARI. Pooled nasal and throat swabs were tested using multiplex real-time PCR for 33 respiratory pathogens (FTD(®) kit). A total of 383 patients were included, 277 (72.3%) of whom presented with pneumonia. 377 (98.4%) patients were positive for at least one microorganism, of which RSV was the most common virus (41.0%), with a peak observed between June and September, corresponding to the rainy season. Most RSV inpatients had pneumonia (84.1%), of whom 35% had severe pneumonia. Children <3-months old were a high-risk group for severe pneumonia, independently of RSV infection. Our study suggests that RSV infection is frequent in Laos and commonly associated with pneumonia in hospitalized young children. Further investigations are required to provide a better overall view of the Lao nationwide epidemiology and public health burden of RSV infection over time.",2017 Aug 24,"['Nguyen, Van Hoan', 'Dubot-Pérès, Audrey', 'Russell, Fiona M.', 'Dance, David A. B.', 'Vilivong, Keoudomphone', 'Phommachan, Souphatsone', 'Syladeth, Chanthaphone', 'Lai, Jana', 'Lim, Ruth', 'Morpeth, Melinda', 'Mayxay, Mayfong', 'Newton, Paul N.', 'Richet, Hervé', 'De Lamballerie, Xavier']",Sci Rep,,,True
a56bc2a490d1558f0fceb37fe4375874dea4453c,PMC,"Complete Genome Characterization of the Porcine Deltacoronavirus HKD/JPN/2016, Isolated in Japan, 2016",http://dx.doi.org/10.1128/genomeA.00795-17,PMC5571404,28839018,CC BY,"In 2016, an outbreak of diarrhea with high mortality in piglets occurred on a swine farm in Hokkaido prefecture, Japan. The causative porcine deltacoronavirus HDK/JPN/2016 was isolated from intestinal samples of the dead piglets on LLC-PK1 cells. The complete genome of HKD/JPN/2016 was sequenced and analyzed by next-generation sequencing technology.",2017 Aug 24,"['Suzuki, Tohru', 'Hayakawa, Jun', 'Ohashi, Seiichi']",Genome Announc,,,True
13fbc589f8307a0f1a6c7eccd2651743c780bd6a,PMC,"Complete Genome Sequence of Porcine Deltacoronavirus Strain CH/JXJGS01/2016, Isolated in Jiangxi Province, China, 2016",http://dx.doi.org/10.1128/genomeA.00832-17,PMC5571410,28839024,CC BY,"The complete genome sequence of a variant of porcine deltacoronavirus, isolated from a diarrheal piglet and designated CH/JXJGS01/2016, was sequenced and analyzed. Phylogenetic analysis demonstrated that CH/JXJGS01/2016 shares the highest nucleotide and amino acid identities with the Chinese strain NH (GenBank accession number KU981059).",2017 Aug 24,"['Zhang, Min', 'Ye, Yu', 'Gong, Wang', 'Guo, Nannan', 'Zhang, Fanfan', 'Li, Anqi', 'Zhou, Xingrong', 'Huang, Dongyan', 'Song, Deping', 'Tang, Yuxin']",Genome Announc,,,True
45ba3b5b8fa3bda8382468b68cff5c361b6569e1,PMC,Rapid development of vaccines against emerging pathogens: The replication-deficient simian adenovirus platform technology,http://dx.doi.org/10.1016/j.vaccine.2017.04.085,PMC5571606,28576573,CC BY,"Despite the fact that there had been multiple small outbreaks of Ebola Virus Disease, when a large outbreak occurred in 2014 there were no vaccines or drugs available for use. Clinical development of multiple candidate vaccines was then initiated in parallel with attempts to contain the outbreak but only one vaccine was eventually tested in a phase III trial. In order to be better prepared for future outbreaks of known human pathogens, platform technologies to accelerate vaccine development should be employed, allowing vaccine developers to take advantage of detailed knowledge of the vaccine platform and facilitating rapid progress to clinical trials and eventually to vaccine stockpiles. This review gives an example of one such vaccine platform, replication-deficient simian adenoviruses, and describes progress in human and livestock vaccine development for three outbreak pathogens, Ebola virus, Rift Valley Fever Virus and Middle East Respiratory Syndrome Coronavirus.",2017 Aug 16,"['Gilbert, Sarah C.', 'Warimwe, George M.']",Vaccine,,,False
aba0193185525dbd5c85f38245bcd05861ec4513,PMC,Zika Virus: What Have We Learnt Since the Start of the Recent Epidemic?,http://dx.doi.org/10.3389/fmicb.2017.01554,PMC5572254,28878742,CC BY,"Zika is a viral disease transmitted mainly by mosquitoes of the genus Aedes. In recent years, it has expanded geographically, changing from an endemic mosquito-borne disease across equatorial Asia and Africa, to an epidemic disease causing large outbreaks in several areas of the world. With the recent Zika virus (ZIKV) outbreaks in the Americas, the disease has become a focus of attention of public health agencies and of the international research community, especially due to an association with neurological disorders in adults and to the severe neurological and ophthalmological abnormalities found in fetuses and newborns of mothers exposed to ZIKV during pregnancy. A large number of studies have been published in the last 3 years, revealing the structure of the virus, how it is transmitted and how it affects human cells. Many different animal models have been developed, which recapitulate several features of ZIKV disease and its neurological consequences. Moreover, several vaccine candidates are now in active preclinical development, and three of them have already entered phase I clinical trials. Likewise, many different compounds targeting viral and cellular components are being tested in in vitro and in experimental animal models. This review aims to discuss the current state of this rapidly growing literature from a multidisciplinary perspective, as well as to present an overview of the public health response to Zika and of the perspectives for the prevention and treatment of this disease.",2017 Aug 22,"['Saiz, Juan-Carlos', 'Martín-Acebes, Miguel A.', 'Bueno-Marí, Rubén', 'Salomón, Oscar D.', 'Villamil-Jiménez, Luis C.', 'Heukelbach, Jorg', 'Alencar, Carlos H.', 'Armstrong, Paul K.', 'Ortiga-Carvalho, Tania M.', 'Mendez-Otero, Rosalia', 'Rosado-de-Castro, Paulo H.', 'Pimentel-Coelho, Pedro M.']",Front Microbiol,,,True
17fe16cf66ebbe693a2e75dda11d14513fec7519,PMC,A Stakeholder Survey on Live Bird Market Closures Policy for Controlling Highly Pathogenic Avian Influenza in Vietnam,http://dx.doi.org/10.3389/fvets.2017.00136,PMC5572285,28879203,CC BY,"Extensive research in Vietnam and elsewhere has shown that live bird markets (LBMs) play a significant role in the ecology and zoonotic transmission of avian influenzas (AIs) including H5N1 and H7N9. Vietnam has a large number of LBMs reflecting the consumer preferences for live poultry. Under pressure to mitigate risks for H7N9 and other zoonotic AIs, Vietnam is considering, among other mitigation measures, temporary closures of LBMs as a policy to reduce risk of AI outbreaks. However, the efficacy of market closure is debated, particularly because little is known about how poultry traders may react, and whether trading may emerge outside formal marketplaces. Combining efforts of anthropologists, economists, sociologists, and veterinarians can be useful to elucidate the drivers behind poultry traders’ reactions and better understanding the barriers to implementing risk mitigation measures. In this paper, we present results from a stakeholder survey of LBM stakeholders in Vietnam. Our qualitative data show that trading outside formal markets is very likely to occur in the event of a temporary LBM market closure. Our data show that the poultry value chain in Vietnam remains highly flexible, with traders willing and able to trade poultry in many possible locations. Our results indicate that simplification of the poultry value chain along with strict enforcement, engagement of stakeholders, and adequate communication would be a necessary prerequisite before market closure could be an effective policy.",2017 Aug 22,"['Nguyen, Thi Thanh Thuy', 'Fearnley, Lyle', 'Dinh, Xuan Tung', 'Tran, Thi Tram Anh', 'Tran, Trong Tung', 'Nguyen, Van Trong', 'Tago, Damian', 'Padungtod, Pawin', 'Newman, Scott H.', 'Tripodi, Astrid']",Front Vet Sci,,,True
1cd1d321b575ccec089326f7b5d66d44e5c99bed,PMC,"Imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection from Oman to Thailand, June 2015",http://dx.doi.org/10.2807/1560-7917.ES.2017.22.33.30598,PMC5572941,28840828,CC BY,"Thailand reported the first Middle East respiratory syndrome (MERS) case on 18 June 2015 (day 4) in an Omani patient with heart condition who was diagnosed with pneumonia on hospital admission on 15 June 2015 (day 1). Two false negative RT-PCR on upper respiratory tract samples on days 2 and 3 led to a 48-hour diagnosis delay and a decision to transfer the patient out of the negative pressure unit (NPU). Subsequent examination of sputum later on day 3 confirmed MERS coronavirus (MERS-CoV) infection. The patient was immediately moved back into the NPU and then transferred to Bamrasnaradura Infectious Disease Institute. Over 170 contacts were traced; 48 were quarantined and 122 self-monitored for symptoms. High-risk close contacts exhibiting no symptoms, and whose laboratory testing on the 12th day after exposure was negative, were released on the 14th day. The Omani Ministry of Health (MOH) was immediately notified using the International Health Regulation (IHR) mechanism. Outbreak investigation was conducted in Oman, and was both published on the World Health Organization (WHO) intranet and shared with Thailand’s IHR focal point. The key to successful infection control, with no secondary transmission, were the collaborative efforts among hospitals, laboratories and MOHs of both countries.",2017 Aug 17,"['Plipat, Tanarak', 'Buathong, Rome', 'Wacharapluesadee, Supaporn', 'Siriarayapon, Potjaman', 'Pittayawonganon, Chakrarat', 'Sangsajja, Chariya', 'Kaewpom, Thongchai', 'Petcharat, Sininat', 'Ponpinit, Teerada', 'Jumpasri, Jaruphan', 'Joyjinda, Yutthana', 'Rodpan, Apaporn', 'Ghai, Siriporn', 'Jittmittraphap, Akanitt', 'Khongwichit, Sarawut', 'Smith, Duncan R', 'Corman, Victor M', 'Drosten, Christian', 'Hemachudha, Thiravat']",Euro Surveill,,,True
160c4bd7c9401bed81b339157fa4ab54242ca8ff,PMC,RNA sequencing demonstrates large-scale temporal dysregulation of gene expression in stimulated macrophages derived from MHC-defined chicken haplotypes,http://dx.doi.org/10.1371/journal.pone.0179391,PMC5573159,28846708,CC BY,"Discovering genetic biomarkers associated with disease resistance and enhanced immunity is critical to developing advanced strategies for controlling viral and bacterial infections in different species. Macrophages, important cells of innate immunity, are directly involved in cellular interactions with pathogens, the release of cytokines activating other immune cells and antigen presentation to cells of the adaptive immune response. IFNγ is a potent activator of macrophages and increased production has been associated with disease resistance in several species. This study characterizes the molecular basis for dramatically different nitric oxide production and immune function between the B2 and the B19 haplotype chicken macrophages.A large-scale RNA sequencing approach was employed to sequence the RNA of purified macrophages from each haplotype group (B2 vs. B19) during differentiation and after stimulation. Our results demonstrate that a large number of genes exhibit divergent expression between B2 and B19 haplotype cells both prior and after stimulation. These differences in gene expression appear to be regulated by complex epigenetic mechanisms that need further investigation.",2017 Aug 28,"['Irizarry, Kristopher J. L.', 'Downs, Eileen', 'Bryden, Randall', 'Clark, Jory', 'Griggs, Lisa', 'Kopulos, Renee', 'Boettger, Cynthia M.', 'Carr, Thomas J.', 'Keeler, Calvin L.', 'Collisson, Ellen', 'Drechsler, Yvonne']",PLoS One,,,True
bd5e22fa122a78846797a754e1dcb12887036229,PMC,A Novel Dynamic Model Describing the Spread of the MERS-CoV and the Expression of Dipeptidyl Peptidase 4,http://dx.doi.org/10.1155/2017/5285810,PMC5574235,28894474,CC BY,"The Middle East respiratory syndrome (MERS) coronavirus, a newly identified pathogen, causes severe pneumonia in humans. MERS is caused by a coronavirus known as MERS-CoV, which attacks the respiratory system. The recently defined receptor for MERS-CoV, dipeptidyl peptidase 4 (DPP4), is generally expressed in endothelial and epithelial cells and has been shown to be present on cultured human nonciliated bronchiolar epithelium cells. In this paper, a class of novel four-dimensional dynamic model describing the infection of MERS-CoV is given, and then global stability of the equilibria of the model is discussed. Our results show that the spread of MERS-CoV can also be controlled by decreasing the expression rate of DPP4.",2017 Aug 15,"['Tang, Siming', 'Ma, Wanbiao', 'Bai, Peifan']",Comput Math Methods Med,,,True
555a36d1c3822baa8b6a2612b86ed5df5b1dbf7c,PMC,Enhanced inflammation in New Zealand white rabbits when MERS-CoV reinfection occurs in the absence of neutralizing antibody,http://dx.doi.org/10.1371/journal.ppat.1006565,PMC5574614,28817732,CC0,"The Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that was first detected in humans in 2012 as a cause of severe acute respiratory disease. As of July 28, 2017, there have been 2,040 confirmed cases with 712 reported deaths. While many infections have been fatal, there have also been a large number of mild or asymptomatic cases discovered through monitoring and contact tracing. New Zealand white rabbits are a possible model for asymptomatic infection with MERS-CoV. In order to discover more about non-lethal infections and to learn whether a single infection with MERS-CoV would protect against reinfection, we inoculated rabbits with MERS-CoV and monitored the antibody and inflammatory response. Following intranasal infection, rabbits developed a transient dose-dependent pulmonary infection with moderately high levels of viral RNA, viral antigen, and perivascular inflammation in multiple lung lobes that was not associated with clinical signs. The rabbits developed antibodies against viral proteins that lacked neutralizing activity and the animals were not protected from reinfection. In fact, reinfection resulted in enhanced pulmonary inflammation, without an associated increase in viral RNA titers. Interestingly, passive transfer of serum from previously infected rabbits to naïve rabbits was associated with enhanced inflammation upon infection. We further found this inflammation was accompanied by increased recruitment of complement proteins compared to primary infection. However, reinfection elicited neutralizing antibodies that protected rabbits from subsequent viral challenge. Our data from the rabbit model suggests that people exposed to MERS-CoV who fail to develop a neutralizing antibody response, or persons whose neutralizing antibody titers have waned, may be at risk for severe lung disease on re-exposure to MERS-CoV.",2017 Aug 17,"['Houser, Katherine V.', 'Broadbent, Andrew J.', 'Gretebeck, Lisa', 'Vogel, Leatrice', 'Lamirande, Elaine W.', 'Sutton, Troy', 'Bock, Kevin W.', 'Minai, Mahnaz', 'Orandle, Marlene', 'Moore, Ian N.', 'Subbarao, Kanta']",PLoS Pathog,,,True
86410d14ac553ca694a7f5324a56b34a0fb6b8fe,PMC,First genome report and analysis of chicken H7N9 influenza viruses with poly-basic amino acids insertion in the hemagglutinin cleavage site,http://dx.doi.org/10.1038/s41598-017-10605-6,PMC5577273,28855633,CC BY,"We report the full-length sequence of two chicken source influenza A (H7N9) viruses found in Guangdong live poultry market (LPM) during the most recent wave of human infections (from October 2016 to the present time). These viruses carry insertion of poly-basic amino acids (KGKRTAR/G) at the protease cleavage site of the HA protein, which were previously found in the highly pathogenic (HP) human influenza A (H7N9) [IAV(H7N9)] strains. Phylogenetic analysis of these two novel avian influenza viruses (AIVs) suggested that their genomes reassorted between the Yangtze River Delta (YRD) and Pearl River Delta (PRD) clades. Molecular clock analysis indicated that they emerged several months before the HP human strains. Collectively, our results suggest that IAV(H7N9) viruses evolve in chickens through antigenic drift to include a signature HP sequence in the HA gene, which highlights challenges in risk assessment and public health management of IAV(H7N9) infections at the human-animal interface.",2017 Aug 30,"['Chen, Jidang', 'Zhang, Jipei', 'Zhu, Wanjun', 'Zhang, Yishan', 'Tan, Hualong', 'Liu, Minfang', 'Cai, Mingsheng', 'Shen, Jiaren', 'Ly, Hinh', 'Chen, Jianhong']",Sci Rep,,,True
29f7f8a096554d3f4cd512b9e825b72130520f12,PMC,First genome report and analysis of chicken H7N9 influenza viruses with poly-basic amino acids insertion in the hemagglutinin cleavage site,http://dx.doi.org/10.1038/s41598-017-10605-6,PMC5577273,28855633,CC BY,"We report the full-length sequence of two chicken source influenza A (H7N9) viruses found in Guangdong live poultry market (LPM) during the most recent wave of human infections (from October 2016 to the present time). These viruses carry insertion of poly-basic amino acids (KGKRTAR/G) at the protease cleavage site of the HA protein, which were previously found in the highly pathogenic (HP) human influenza A (H7N9) [IAV(H7N9)] strains. Phylogenetic analysis of these two novel avian influenza viruses (AIVs) suggested that their genomes reassorted between the Yangtze River Delta (YRD) and Pearl River Delta (PRD) clades. Molecular clock analysis indicated that they emerged several months before the HP human strains. Collectively, our results suggest that IAV(H7N9) viruses evolve in chickens through antigenic drift to include a signature HP sequence in the HA gene, which highlights challenges in risk assessment and public health management of IAV(H7N9) infections at the human-animal interface.",2017 Aug 30,"['Chen, Jidang', 'Zhang, Jipei', 'Zhu, Wanjun', 'Zhang, Yishan', 'Tan, Hualong', 'Liu, Minfang', 'Cai, Mingsheng', 'Shen, Jiaren', 'Ly, Hinh', 'Chen, Jianhong']",Sci Rep,,,True
ffb147f62b6570ee48fa765305c24ebcc8e4912f,PMC,A Novel High-Mannose Specific Lectin from the Green Alga Halimeda renschii Exhibits a Potent Anti-Influenza Virus Activity through High-Affinity Binding to the Viral Hemagglutinin,http://dx.doi.org/10.3390/md15080255,PMC5577609,28813016,CC BY,"We have isolated a novel lectin, named HRL40 from the green alga Halimeda renschii. In hemagglutination-inhibition test and oligosaccharide-binding experiment with 29 pyridylaminated oligosaccharides, HRL40 exhibited a strict binding specificity for high-mannose N-glycans having an exposed (α1-3) mannose residue in the D2 arm of branched mannosides, and did not have an affinity for monosaccharides and other oligosaccharides examined, including complex N-glycans, an N-glycan core pentasaccharide, and oligosaccharides from glycolipids. The carbohydrate binding profile of HRL40 resembled those of Type I high-mannose specific antiviral algal lectins, or the Oscillatoria agardhii agglutinin (OAA) family, which were previously isolated from red algae and a blue-green alga (cyanobacterium). HRL40 potently inhibited the infection of influenza virus (A/H3N2/Udorn/72) into NCI-H292 cells with half-maximal effective dose (ED(50)) of 2.45 nM through high-affinity binding to a viral envelope hemagglutinin (K(D), 3.69 × 10(−11) M). HRL40 consisted of two isolectins (HRL40-1 and HRL40-2), which could be separated by reverse-phase HPLC. Both isolectins had the same molecular weight of 46,564 Da and were a disulfide -linked tetrameric protein of a 11,641 Da polypeptide containing at least 13 half-cystines. Thus, HRL40, which is the first Type I high-mannose specific antiviral lectin from the green alga, had the same carbohydrate binding specificity as the OAA family, but a molecular structure distinct from the family.",2017 Aug 16,"['Mu, Jinmin', 'Hirayama, Makoto', 'Sato, Yuichiro', 'Morimoto, Kinjiro', 'Hori, Kanji']",Mar Drugs,,,True
f9b05dd5d6e92dda6775f003c85d17e94952e78c,PMC,A Novel High-Mannose Specific Lectin from the Green Alga Halimeda renschii Exhibits a Potent Anti-Influenza Virus Activity through High-Affinity Binding to the Viral Hemagglutinin,http://dx.doi.org/10.3390/md15080255,PMC5577609,28813016,CC BY,"We have isolated a novel lectin, named HRL40 from the green alga Halimeda renschii. In hemagglutination-inhibition test and oligosaccharide-binding experiment with 29 pyridylaminated oligosaccharides, HRL40 exhibited a strict binding specificity for high-mannose N-glycans having an exposed (α1-3) mannose residue in the D2 arm of branched mannosides, and did not have an affinity for monosaccharides and other oligosaccharides examined, including complex N-glycans, an N-glycan core pentasaccharide, and oligosaccharides from glycolipids. The carbohydrate binding profile of HRL40 resembled those of Type I high-mannose specific antiviral algal lectins, or the Oscillatoria agardhii agglutinin (OAA) family, which were previously isolated from red algae and a blue-green alga (cyanobacterium). HRL40 potently inhibited the infection of influenza virus (A/H3N2/Udorn/72) into NCI-H292 cells with half-maximal effective dose (ED(50)) of 2.45 nM through high-affinity binding to a viral envelope hemagglutinin (K(D), 3.69 × 10(−11) M). HRL40 consisted of two isolectins (HRL40-1 and HRL40-2), which could be separated by reverse-phase HPLC. Both isolectins had the same molecular weight of 46,564 Da and were a disulfide -linked tetrameric protein of a 11,641 Da polypeptide containing at least 13 half-cystines. Thus, HRL40, which is the first Type I high-mannose specific antiviral lectin from the green alga, had the same carbohydrate binding specificity as the OAA family, but a molecular structure distinct from the family.",2017 Aug 16,"['Mu, Jinmin', 'Hirayama, Makoto', 'Sato, Yuichiro', 'Morimoto, Kinjiro', 'Hori, Kanji']",Mar Drugs,,,False
6a0f7cfb9306380e01f35d7f8c0e75c0f91dcbc4,PMC,Identification of two mutation sites in spike and envelope proteins mediating optimal cellular infection of porcine epidemic diarrhea virus from different pathways,http://dx.doi.org/10.1186/s13567-017-0449-y,PMC5577753,28854955,CC BY,"Entry of the α-coronavirus porcine epidemic diarrhea virus (PEDV) requires specific proteases to activate spike (S) protein for the membrane fusion of the virion to the host cell following receptor binding. Herein, PEDV isolate 85-7 could proliferate and induce cell–cell fusion in a trypsin independent manner on Vero cells, and eight homologous mutation strains were screened by continuous proliferation in the absence of trypsin on Vero cells. According to the whole genome sequence comparative analysis, we identified four major variations located in nonstructural protein 2, S, open reading frame 3, and envelope (E) genes, respectively. Comparative analyses of their genomic variations and proliferation characteristics identified a single mutation within the S2′ cleavage site between C30 and C40 mutants: the substitution of conserved arginine (R) by a glycine (G) (R895G). This change resulted in weaker cell–cell fusion, smaller plaque morphology, higher virus titer and serious microfilament condensation. Further analysis confirmed that this mutation was responsible for optimal cell-adaptation, but not the determinant for trypsin-dependent entry of PEDV. Otherwise, a novel variation (16–20 aa deletion and an L25P mutation) in the transmembrane domain of the E protein affected multiple infection processes, including up-regulation of the production of the ER stress indicator GRP78, improving the expression of pro-inflammatory cytokines IL-6 and IL-8, and promoting apoptosis. The results of this study provide a better understanding of the potential mechanisms of viral functional proteins in PEDV replication, infection, and fitness. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-017-0449-y) contains supplementary material, which is available to authorized users.",2017 Aug 30,"['Sun, Min', 'Ma, Jiale', 'Yu, Zeyanqiu', 'Pan, Zihao', 'Lu, Chengping', 'Yao, Huochun']",Vet Res,,,True
1f4c7f7b1707f71e188cc621e323bd5751b3e6a8,PMC,Chemical Modifications of Nucleic Acid Aptamers for Therapeutic Purposes,http://dx.doi.org/10.3390/ijms18081683,PMC5578073,28767098,CC BY,"Nucleic acid aptamers have minimal immunogenicity, high chemical synthesis production, low cost and high chemical stability when compared with antibodies. However, the susceptibility to nuclease degradation, rapid excretion through renal filtration and insufficient binding affinity hindered their development as drug candidates for therapeutic applications. In this review, we will discuss methods to conquer these challenges and highlight recent developments of chemical modifications and technological advances that may enable early aptamers to be translated into clinical therapeutics.",2017 Aug 2,"['Ni, Shuaijian', 'Yao, Houzong', 'Wang, Lili', 'Lu, Jun', 'Jiang, Feng', 'Lu, Aiping', 'Zhang, Ge']",Int J Mol Sci,,,True
90672df8690ad900302e0e94fbe073b7cb762458,PMC,Infectious Bronchitis Virus Infection Induces Apoptosis during Replication in Chicken Macrophage HD11 Cells,http://dx.doi.org/10.3390/v9080198,PMC5580455,28933760,CC BY,"Avian infectious bronchitis has caused huge economic losses in the poultry industry. Previous studies have reported that infectious bronchitis virus (IBV) infection can produce cytopathic effects (CPE) and apoptosis in some mammalian cells and primary cells. However, there is little research on IBV-induced immune cell apoptosis. In this study, chicken macrophage HD11 cells were established as a cellular model that is permissive to IBV infection. Then, IBV-induced apoptosis was observed through a cell viability assay, morphological changes, and flow cytometry. The activity of caspases, the inhibitory efficacy of caspase-inhibitors and the expression of apoptotic genes further suggested the activation of apoptosis through both intrinsic and extrinsic pathways in IBV-infected HD11 cells. Additionally, ammonium chloride (NH(4)Cl) pretreated HD11 cells blocked IBV from entering cells and inhibited IBV-induced apoptosis. UV-inactivated IBV also lost the ability of apoptosis induction. IBV replication was increased by blocking caspase activation. This study presents a chicken macrophage cell line that will enable further analysis of IBV infection and offers novel insights into the mechanisms of IBV-induced apoptosis in immune cells.",2017 Jul 26,"['Han, Xiaoxiao', 'Tian, Yiming', 'Guan, Ru', 'Gao, Wenqian', 'Yang, Xin', 'Zhou, Long', 'Wang, Hongning']",Viruses,,,True
f54b1d2032db8537d80fc36e29bc6fcdfb878435,PMC,Characterization of Monoclonal Antibodies against HA Protein of H1N1 Swine Influenza Virus and Protective Efficacy against H1 Viruses in Mice,http://dx.doi.org/10.3390/v9080209,PMC5580466,28786930,CC BY,"H1N1 swine influenza viruses (SIV) are prevalent in pigs globally, and occasionally emerge in humans, which raises concern about their pandemic threats. To stimulate hemagglutination (HA) of A/Swine/Guangdong/LM/2004 (H1N1) (SW/GD/04) antibody response, eukaryotic expression plasmid pCI-neo-HA was constructed and used as an immunogen to prepare monoclonal antibodies (mAbs). Five mAbs (designed 8C4, 8C6, 9D6, 8A4, and 8B1) against HA protein were obtained and characterized. Western blot showed that the 70 kDa HA protein could be detected by all mAbs in MDCK cells infected with SW/GD/04. Three mAbs—8C4, 8C6, and 9D6—have hemagglutination inhibition (HI) and neutralization test (NT) activities, and 8C6 induces the highest HI and NT titers. The protection efficacy of 8C6 was investigated in BALB/c mice challenged with homologous or heterologous strains of the H1 subtype SIV. The results indicate that mAb 8C6 protected the mice from viral infections, especially the homologous strain, which was clearly demonstrated by the body weight changes and reduction of viral load. Thus, our findings document for the first time that mAb 8C6 might be of potential therapeutic value for H1 subtype SIV infection.",2017 Aug 8,"['Liu, Yun', 'Li, Hongtao', 'Xue, Yujia', 'Zhao, Shuang', 'Li, Chenxi', 'Qu, Liandong', 'Zhang, Yun', 'Liu, Ming']",Viruses,,,True
719011222a3dd0642fb565e5f80fa03a184835eb,PMC,Characterization of a Novel RNA Virus Discovered in the Autumnal Moth Epirrita autumnata in Sweden,http://dx.doi.org/10.3390/v9080214,PMC5580471,,CC BY,"A novel, 10 kb RNA virus—tentatively named ‘Abisko virus’—was discovered in the transcriptome data of a diseased autumnal moth (Epirrita autumnata) larva, as part of a search for the possible causes of the cyclical nature and mortality associated with geometrid moth dynamics and outbreaks in northern Fennoscandia. Abisko virus has a genome organization similar to that of the insect-infecting negeviruses, but phylogenetic and compositional bias analyses also reveal strong affiliations with plant-infecting viruses, such that both the primary host origin and taxonomic identity of the virus remain in doubt. In an extensive set of larval, pupal, and adult autumnal moth and winter moth (Operophtera brumata) outbreak samples, the virus was only detected in a few adult E. autumnata moths as well as the single larval transcriptome. The Abisko virus is therefore unlikely to be a factor in the Fennoscandia geometrid population dynamics.",2017 Aug 8,"['de Miranda, Joachim R.', 'Hedman, Harald', 'Onorati, Piero', 'Stephan, Jörg', 'Karlberg, Olof', 'Bylund, Helena', 'Terenius, Olle']",Viruses,,,True
9c63fefd305d880bb2237d14dea23d5955949ea7,PMC,Characterization of a Novel RNA Virus Discovered in the Autumnal Moth Epirrita autumnata in Sweden,http://dx.doi.org/10.3390/v9080214,PMC5580471,,CC BY,"A novel, 10 kb RNA virus—tentatively named ‘Abisko virus’—was discovered in the transcriptome data of a diseased autumnal moth (Epirrita autumnata) larva, as part of a search for the possible causes of the cyclical nature and mortality associated with geometrid moth dynamics and outbreaks in northern Fennoscandia. Abisko virus has a genome organization similar to that of the insect-infecting negeviruses, but phylogenetic and compositional bias analyses also reveal strong affiliations with plant-infecting viruses, such that both the primary host origin and taxonomic identity of the virus remain in doubt. In an extensive set of larval, pupal, and adult autumnal moth and winter moth (Operophtera brumata) outbreak samples, the virus was only detected in a few adult E. autumnata moths as well as the single larval transcriptome. The Abisko virus is therefore unlikely to be a factor in the Fennoscandia geometrid population dynamics.",2017 Aug 8,"['de Miranda, Joachim R.', 'Hedman, Harald', 'Onorati, Piero', 'Stephan, Jörg', 'Karlberg, Olof', 'Bylund, Helena', 'Terenius, Olle']",Viruses,,,False
826307b42adef6c0aa282ada8ec07afb1b35cb3e,PMC,Inhibitors of Deubiquitinating Enzymes Block HIV-1 Replication and Augment the Presentation of Gag-Derived MHC-I Epitopes,http://dx.doi.org/10.3390/v9080222,PMC5580479,28805676,CC BY,"In recent years it has been well established that two major constituent parts of the ubiquitin proteasome system (UPS)—the proteasome holoenzymes and a number of ubiquitin ligases—play a crucial role, not only in virus replication but also in the regulation of the immunogenicity of human immunodeficiency virus type 1 (HIV-1). However, the role in HIV-1 replication of the third major component, the deubiquitinating enzymes (DUBs), has remained largely unknown. In this study, we show that the DUB-inhibitors (DIs) P22077 and PR-619, specific for the DUBs USP7 and USP47, impair Gag processing and thereby reduce the infectivity of released virions without affecting viral protease activity. Furthermore, the replication capacity of X4- and R5-tropic HIV-1(NL4-3) in human lymphatic tissue is decreased upon treatment with these inhibitors without affecting cell viability. Most strikingly, combinatory treatment with DIs and proteasome inhibitors synergistically blocks virus replication at concentrations where mono-treatment was ineffective, indicating that DIs can boost the therapeutic effect of proteasome inhibitors. In addition, P22077 and PR-619 increase the polyubiquitination of Gag and thus its entry into the UPS and the major histocompatibility complex (MHC)-I pathway. In summary, our data point towards a model in which specific inhibitors of DUBs not only interfere with virus spread but also increase the immune recognition of HIV-1 expressing cells.",2017 Aug 12,"['Setz, Christian', 'Friedrich, Melanie', 'Rauch, Pia', 'Fraedrich, Kirsten', 'Matthaei, Alina', 'Traxdorf, Maximilian', 'Schubert, Ulrich']",Viruses,,,True
069a3aebc920d5da476fef73fd5d47566c780885,PMC,"Disentangling the Frames, the State of Research on the Alphavirus 6K and TF Proteins",http://dx.doi.org/10.3390/v9080228,PMC5580485,28820485,CC BY,"For 30 years it was thought the alphavirus 6K gene encoded a single 6 kDa protein. However, through a bioinformatics search 10 years ago, it was discovered that there is a frameshifting event and two proteins, 6K and transframe (TF), are translated from the 6K gene. Thus, many functions attributed to the 6K protein needed reevaluation to determine if they properly belong to 6K, TF, or both proteins. In this mini-review, we reevaluate the past research on 6K and put those results in context where there are two proteins, 6K and TF, instead of one. Additionally, we discuss the most cogent outstanding questions for 6K and TF research, including their collective importance in alphavirus budding and their potential importance in disease based on the latest virulence data.",2017 Aug 18,"['Ramsey, Jolene', 'Mukhopadhyay, Suchetana']",Viruses,,,True
7fbdfc090a8be95eb166a2d66dd91b7a51d11570,PMC,Specialty Grand Challenge In Pediatric Infectious Diseases,http://dx.doi.org/10.3389/fped.2017.00185,PMC5581326,28894730,CC BY,,2017 Aug 28,"['Lepage, Philippe', 'Blumental, Sophie']",Front Pediatr,,,True
620df0595486589bbc677f72cc78f2d158b9810c,PMC,In Silico Perspectives on the Prediction of the PLP’s Epitopes involved in Multiple Sclerosis,http://dx.doi.org/10.15171/ijb.1356,PMC5582249,28959348,CC BY,"BACKGROUND: Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS). The main cause of the MS is yet to be revealed, but the most probable theory is based on the molecular mimicry that concludes some infections in the activation of T cells against brain auto-antigens that initiate the disease cascade. OBJECTIVES: The Purpose of this research is the prediction of the auto-antigen potency of the myelin proteolipid protein (PLP) in multiple sclerosis. MATERIALS AND METHODS: As there wasn’t any tertiary structure of PLP available in the Protein Data Bank (PDB) and in order to characterize the structural properties of the protein, we modeled this protein using prediction servers. Meta prediction method, as a new perspective in silico, was performed to fi nd PLPs epitopes. For this purpose, several T cell epitope prediction web servers were used to predict PLPs epitopes against Human Leukocyte Antigens (HLA). The overlap regions, as were predicted by most web servers were selected as immunogenic epitopes and were subjected to the BLASTP against microorganisms. RESULTS: Three common regions, AA(58-74), AA(161-177), and AA(238-254) were detected as immunodominant regions through meta-prediction. Investigating peptides with more than 50% similarity to that of candidate epitope AA(58-74) in bacteria showed a similar peptide in bacteria (mainly consistent with that of clostridium and mycobacterium) and spike protein of Alphacoronavirus 1, Canine coronavirus, and Feline coronavirus. These results suggest that cross reaction of the immune system to PLP may have originated from a bacteria or viral infection, and therefore molecular mimicry might have an important role in the progression of MS. CONCLUSIONS: Through reliable and accurate prediction of the consensus epitopes, it is not necessary to synthesize all PLP fragments and examine their immunogenicity experimentally (in vitro). In this study, the best encephalitogenic antigens were predicted based on bioinformatics tools that may provide reliable results for researches in a shorter time and at a lower cost.",2017 Mar,"['Zamanzadeh, Zahra', 'Ataei, Mitra', 'Nabavi, Seyed Massood', 'Ahangari, Ghasem', 'Sadeghi, Mehdi', 'Sanati, Mohammad Hosein']",Iran J Biotechnol,,,True
7a16fe9d867203bf83dfe50ef6dd93b8e1179db7,PMC,Immunization with Live Human Rhinovirus (HRV) 16 Induces Protection in Cotton Rats against HRV14 Infection,http://dx.doi.org/10.3389/fmicb.2017.01646,PMC5583225,28912760,CC BY,"Human rhinoviruses (HRVs) are the main cause of cold-like illnesses, and currently no vaccine or antiviral therapies against HRVs are available to prevent or mitigate HRV infection. There are more than 150 antigenically heterogeneous HRV serotypes, with ∼90 HRVs belonging to major group species A and B. Development of small animal models that are susceptible to infection with major group HRVs would be beneficial for vaccine research. Previously, we showed that the cotton rat (Sigmodon hispidus) is semi-permissive to HRV16 (major group, species HRV-A virus) infection, replicating in the upper and lower respiratory tracts with measurable pathology, mucus production, and expression of inflammatory mediators. Herein, we report that intranasal infection of cotton rats with HRV14 (major group, species HRV-B virus) results in isolation of infectious virus from the nose and lung. Similar to HRV16, intramuscular immunization with live HRV14 induces homologous protection that correlated with high levels of serum neutralizing antibodies. Vaccination and challenge experiments with HRV14 and HRV16 to evaluate the development of cross-protective immunity demonstrate that intramuscular immunization with live HRV16 significantly protects animals against HRV14 challenge. Determination of the immunological mechanisms involved in heterologous protection and further characterization of infection with other major HRV serotypes in the cotton rat could enhance the robustness of the model to define heterotypic relationships between this diverse group of viruses and thereby increase its potential for development of a multi-serotype HRV vaccine.",2017 Aug 31,"['Patel, Mira C.', 'Pletneva, Lioubov M.', 'Boukhvalova, Marina S.', 'Vogel, Stefanie N.', 'Kajon, Adriana E.', 'Blanco, Jorge C. G.']",Front Microbiol,,,True
61fabfc758361c0d84c86c3d735de857d9537b94,PMC,A novel quantitative PCR mediated by high-fidelity DNA polymerase,http://dx.doi.org/10.1038/s41598-017-10782-4,PMC5583327,28871131,CC BY,"The biggest challenge for accurate diagnosis of viral infectious disease is the high genetic variability of involved viruses, which affects amplification efficiency and results in low sensitivity and narrow spectrum. Here, we developed a new simple qPCR mediated by high-fidelity (HF) DNA polymerase. The new method utilizes an HFman probe and one primer. Fluorescent signal was generated from the 3′–5′ hydrolysis of HFman probe by HF DNA polymerase before elongation initiation. Mismatches between probe/primer and template have less influence on the amplification efficiency of the new method. The new qPCR exhibited higher sensitivity and better adaptability to sequence variable templates than the conventional TaqMan probe based-qPCR in quantification of HIV-1 viral load. Further comparison with COBAS TaqMan HIV-1 Test (v2.0) showed a good correlation coefficient (R(2) = 0.79) between both methods in quantification of HIV-1 viral load among 21 clinical samples. The characteristics of tolerance to variable templates and one probe-one primer system imply that the probe/primer design for the new method will be easier and more flexible than the conventional method for highly heterogeneous viruses. Therefore, the HF DNA polymerase-mediated qPCR method is a simple, sensitive and promising approach for the development of diagnostics for viral infectious diseases.",2017 Sep 4,"['Zhang, Mengling', 'Liu, Kyle', 'Hu, Yihong', 'Lin, Yi', 'Li, Yang', 'Zhong, Ping', 'Jin, Xia', 'Zhu, Xiaoli', 'Zhang, Chiyu']",Sci Rep,,,True
d55ee40e7898b693872356e1661f658732984bae,PMC,A novel quantitative PCR mediated by high-fidelity DNA polymerase,http://dx.doi.org/10.1038/s41598-017-10782-4,PMC5583327,28871131,CC BY,"The biggest challenge for accurate diagnosis of viral infectious disease is the high genetic variability of involved viruses, which affects amplification efficiency and results in low sensitivity and narrow spectrum. Here, we developed a new simple qPCR mediated by high-fidelity (HF) DNA polymerase. The new method utilizes an HFman probe and one primer. Fluorescent signal was generated from the 3′–5′ hydrolysis of HFman probe by HF DNA polymerase before elongation initiation. Mismatches between probe/primer and template have less influence on the amplification efficiency of the new method. The new qPCR exhibited higher sensitivity and better adaptability to sequence variable templates than the conventional TaqMan probe based-qPCR in quantification of HIV-1 viral load. Further comparison with COBAS TaqMan HIV-1 Test (v2.0) showed a good correlation coefficient (R(2) = 0.79) between both methods in quantification of HIV-1 viral load among 21 clinical samples. The characteristics of tolerance to variable templates and one probe-one primer system imply that the probe/primer design for the new method will be easier and more flexible than the conventional method for highly heterogeneous viruses. Therefore, the HF DNA polymerase-mediated qPCR method is a simple, sensitive and promising approach for the development of diagnostics for viral infectious diseases.",2017 Sep 4,"['Zhang, Mengling', 'Liu, Kyle', 'Hu, Yihong', 'Lin, Yi', 'Li, Yang', 'Zhong, Ping', 'Jin, Xia', 'Zhu, Xiaoli', 'Zhang, Chiyu']",Sci Rep,,,True
15da0bac7ba69e867df1af947566ee74e80bdb0e,PMC,Identification of a natural recombinant transmissible gastroenteritis virus between Purdue and Miller clusters in China,http://dx.doi.org/10.1038/emi.2017.62,PMC5583670,28831195,CC BY,"Transmissible gastroenteritis virus (TGEV) is an infective coronavirus (CoV) that causes diarrhea-related morbidity and mortality in piglets. For the first time, a natural recombination strain of a TGEV Anhui Hefei (AHHF) virus between the Purdue and the Miller clusters was isolated from the small intestine content of piglets in China. A phylogenetic tree based on a complete genome sequence placed the TGEV AHHF strain between the Purdue and the Miller clusters. The results of a computational analysis of recombination showed that the TGEV AHHF strain is a natural recombinant strain between these clusters. Two breakpoints located in the open reading frame 1a (ORF1a) and spike (S) genes were identified. The pathogenicity of the TGEV AHHF strain was evaluated in piglets, and the results show that TGEV AHHF is an enteric pathogenic strain. These results provide valuable information about the recombination and evolution of CoVs and will facilitate future investigations of the molecular pathogenesis of TGEV.",2017 Aug 23,"['Zhang, Xin', 'Zhu, Yunnuan', 'Zhu, Xiangdong', 'Shi, Hongyan', 'Chen, Jianfei', 'Shi, Da', 'Yuan, Jing', 'Cao, Liyan', 'Liu, Jianbo', 'Dong, Hui', 'Jing, Zhaoyang', 'Zhang, Jialin', 'Wang, Xiaobo', 'Feng, Li']",Emerg Microbes Infect,,,True
5341fd2caa821b2616a8bc85763a608b29cb4947,PMC,Origins and pathogenesis of Middle East respiratory syndrome-associated coronavirus: recent advances,http://dx.doi.org/10.12688/f1000research.11827.1,PMC5583735,29026532,CC BY,"Middle East respiratory syndrome-associated coronavirus (MERS-CoV) has been a significant research focus since its discovery in 2012. Since 2012, 2,040 cases and 712 deaths have been recorded (as of August 11, 2017), representing a strikingly high case fatality rate of 36%. Over the last several years, MERS-CoV research has progressed in several parallel and complementary directions. This review will focus on three particular areas: the origins and evolution of MERS-CoV, the challenges and achievements in the development of MERS-CoV animal models, and our understanding of how novel proteins unique to MERS-CoV counter the host immune response. The origins of MERS-CoV, likely in African bats, are increasingly clear, although important questions remain about the establishment of dromedary camels as a reservoir seeding human outbreaks. Likewise, there have been important advances in the development of animal models, and both non-human primate and mouse models that seem to recapitulate human disease are now available. How MERS-CoV evades and inhibits the host innate immune response remains less clear. Although several studies have identified MERS-CoV proteins as innate immune antagonists, little of this work has been conducted using live virus under conditions of actual infection, but rather with ectopically expressed proteins. Accordingly, considerable space remains for major contributions to understanding unique ways in which MERS-CoV interacts with and modulates the host response. Collectively, these areas have seen significant advances over the last several years but continue to offer exciting opportunities for discovery.",2017 Sep 1,"['Goldstein, Stephen A.', 'Weiss, Susan R.']",F1000Res,,,True
aa5c3ba1a343c13446ce37073c2e03cf91032f28,PMC,HIV-1 tolerates changes in A-count in a small segment of the pol gene,http://dx.doi.org/10.1186/s12977-017-0367-0,PMC5583962,28870251,CC BY,"BACKGROUND: The HIV-1 RNA genome has a biased nucleotide composition with a surplus of As. Several hypotheses have been put forward to explain this striking phenomenon, but the A-count of the HIV-1 genome has thus far not been systematically manipulated. The reason for this reservation is the likelihood that known and unknown sequence motifs will be affected by such a massive mutational approach, thus resulting in replication-impaired virus mutants. We present the first attempt to increase and decrease the A-count in a relatively small polymerase (pol) gene segment of HIV-1 RNA. RESULTS: To minimize the mutational impact, a new mutational approach was developed that is inspired by natural sequence variation as present in HIV-1 isolates. This phylogeny-instructed mutagenesis allowed us to create replication-competent HIV-1 mutants with a significantly increased or decreased local A-count. The local A-count of the wild-type (wt) virus (40.2%) was further increased to 46.9% or reduced to 31.7 and 26.3%. These HIV-1 variants replicate efficiently in vitro, despite the fact that the pol changes cause a quite profound move in HIV–SIV sequence space. CONCLUSIONS: Extrapolating these results to the complete 9 kb RNA genome, we may cautiously suggest that the A-rich signature does not have to be maintained. This survey also provided clues that silent codon changes, in particular from G-to-A, determine the subtype-specific sequence signatures.",2017 Sep 5,"['Klaver, Bep', 'van der Velden, Yme', 'van Hemert, Formijn', 'van der Kuyl, Antoinette C.', 'Berkhout, Ben']",Retrovirology,,,True
ec333538173a5359e0cc9a31a9f5675d36e7d5c5,PMC,Immunosuppression by viral N proteins,http://dx.doi.org/10.18632/oncotarget.18597,PMC5584132,28881563,CC BY,,2017 Jun 22,"['Chen, Jidang', 'Ly, Hinh']",Oncotarget,,,True
b2eef726fe46a8ddef327c78e7d5affbfd2fe69c,PMC,Coronavirus HKU15 in respiratory tract of pigs and first discovery of coronavirus quasispecies in 5′-untranslated region,http://dx.doi.org/10.1038/emi.2017.37,PMC5584481,28634353,CC BY,"Coronavirus HKU15 is a deltacoronavirus that was discovered in fecal samples of pigs in Hong Kong in 2012. Over the past three years, Coronavirus HKU15 has been widely detected in pigs in East/Southeast Asia and North America and has been associated with fatal outbreaks. In all such epidemiological studies, the virus was generally only detected in fecal/intestinal samples. In this molecular epidemiology study, we detected Coronavirus HKU15 in 9.6% of the nasopharyngeal samples obtained from 249 pigs in Hong Kong. Samples that tested positive were mostly collected during winter. Complete genome sequencing of the Coronavirus HKU15 in two nasopharyngeal samples revealed quasispecies in one of the samples. Two of the polymorphic sites involved indels, but the other two involved transition substitutions. Phylogenetic analysis showed that the two nasopharyngeal strains in the present study were most closely related to the strains PDCoV/CHJXNI2/2015 from Jiangxi, China, and CH/Sichuan/S27/2012 from Sichuan, China. The outbreak strains in the United States possessed highly similar genome sequences and were clustered monophyletically, whereas the Asian strains were more diverse and paraphyletic. The detection of Coronavirus HKU15 in respiratory tracts of pigs implies that in addition to enteric infections, Coronavirus HKU15 may be able to cause respiratory infections in pigs and that in addition to fecal-oral transmission, the virus could possibly spread through the respiratory route. The presence of the virus in respiratory samples provides an alternative clinical sample to confirm the diagnosis of Coronavirus HKU15 infection. Quasispecies were unprecedentedly observed in the 5′-untranslated region of coronavirus genomes.",2017 Jun 21,"['Woo, Patrick CY', 'Lau, Susanna KP', 'Tsang, Chi-Ching', 'Lau, Candy CY', 'Wong, Po-Chun', 'Chow, Franklin WN', 'Fong, Jordan YH', 'Yuen, Kwok-Yung']",Emerg Microbes Infect,,,True
1c1e7e08b864927e86a81a2d6df1f32f4f7d859b,PMC,Coronavirus HKU15 in respiratory tract of pigs and first discovery of coronavirus quasispecies in 5′-untranslated region,http://dx.doi.org/10.1038/emi.2017.37,PMC5584481,28634353,CC BY,"Coronavirus HKU15 is a deltacoronavirus that was discovered in fecal samples of pigs in Hong Kong in 2012. Over the past three years, Coronavirus HKU15 has been widely detected in pigs in East/Southeast Asia and North America and has been associated with fatal outbreaks. In all such epidemiological studies, the virus was generally only detected in fecal/intestinal samples. In this molecular epidemiology study, we detected Coronavirus HKU15 in 9.6% of the nasopharyngeal samples obtained from 249 pigs in Hong Kong. Samples that tested positive were mostly collected during winter. Complete genome sequencing of the Coronavirus HKU15 in two nasopharyngeal samples revealed quasispecies in one of the samples. Two of the polymorphic sites involved indels, but the other two involved transition substitutions. Phylogenetic analysis showed that the two nasopharyngeal strains in the present study were most closely related to the strains PDCoV/CHJXNI2/2015 from Jiangxi, China, and CH/Sichuan/S27/2012 from Sichuan, China. The outbreak strains in the United States possessed highly similar genome sequences and were clustered monophyletically, whereas the Asian strains were more diverse and paraphyletic. The detection of Coronavirus HKU15 in respiratory tracts of pigs implies that in addition to enteric infections, Coronavirus HKU15 may be able to cause respiratory infections in pigs and that in addition to fecal-oral transmission, the virus could possibly spread through the respiratory route. The presence of the virus in respiratory samples provides an alternative clinical sample to confirm the diagnosis of Coronavirus HKU15 infection. Quasispecies were unprecedentedly observed in the 5′-untranslated region of coronavirus genomes.",2017 Jun 21,"['Woo, Patrick CY', 'Lau, Susanna KP', 'Tsang, Chi-Ching', 'Lau, Candy CY', 'Wong, Po-Chun', 'Chow, Franklin WN', 'Fong, Jordan YH', 'Yuen, Kwok-Yung']",Emerg Microbes Infect,,,False
bbef93d881cf1a670831502309ae14fb148822c6,PMC,Coronavirus HKU15 in respiratory tract of pigs and first discovery of coronavirus quasispecies in 5′-untranslated region,http://dx.doi.org/10.1038/emi.2017.37,PMC5584481,28634353,CC BY,"Coronavirus HKU15 is a deltacoronavirus that was discovered in fecal samples of pigs in Hong Kong in 2012. Over the past three years, Coronavirus HKU15 has been widely detected in pigs in East/Southeast Asia and North America and has been associated with fatal outbreaks. In all such epidemiological studies, the virus was generally only detected in fecal/intestinal samples. In this molecular epidemiology study, we detected Coronavirus HKU15 in 9.6% of the nasopharyngeal samples obtained from 249 pigs in Hong Kong. Samples that tested positive were mostly collected during winter. Complete genome sequencing of the Coronavirus HKU15 in two nasopharyngeal samples revealed quasispecies in one of the samples. Two of the polymorphic sites involved indels, but the other two involved transition substitutions. Phylogenetic analysis showed that the two nasopharyngeal strains in the present study were most closely related to the strains PDCoV/CHJXNI2/2015 from Jiangxi, China, and CH/Sichuan/S27/2012 from Sichuan, China. The outbreak strains in the United States possessed highly similar genome sequences and were clustered monophyletically, whereas the Asian strains were more diverse and paraphyletic. The detection of Coronavirus HKU15 in respiratory tracts of pigs implies that in addition to enteric infections, Coronavirus HKU15 may be able to cause respiratory infections in pigs and that in addition to fecal-oral transmission, the virus could possibly spread through the respiratory route. The presence of the virus in respiratory samples provides an alternative clinical sample to confirm the diagnosis of Coronavirus HKU15 infection. Quasispecies were unprecedentedly observed in the 5′-untranslated region of coronavirus genomes.",2017 Jun 21,"['Woo, Patrick CY', 'Lau, Susanna KP', 'Tsang, Chi-Ching', 'Lau, Candy CY', 'Wong, Po-Chun', 'Chow, Franklin WN', 'Fong, Jordan YH', 'Yuen, Kwok-Yung']",Emerg Microbes Infect,,,False
c2dca47102d86d3bb2b4c50a50f862bcecac3912,PMC,Coronavirus HKU15 in respiratory tract of pigs and first discovery of coronavirus quasispecies in 5′-untranslated region,http://dx.doi.org/10.1038/emi.2017.37,PMC5584481,28634353,CC BY,"Coronavirus HKU15 is a deltacoronavirus that was discovered in fecal samples of pigs in Hong Kong in 2012. Over the past three years, Coronavirus HKU15 has been widely detected in pigs in East/Southeast Asia and North America and has been associated with fatal outbreaks. In all such epidemiological studies, the virus was generally only detected in fecal/intestinal samples. In this molecular epidemiology study, we detected Coronavirus HKU15 in 9.6% of the nasopharyngeal samples obtained from 249 pigs in Hong Kong. Samples that tested positive were mostly collected during winter. Complete genome sequencing of the Coronavirus HKU15 in two nasopharyngeal samples revealed quasispecies in one of the samples. Two of the polymorphic sites involved indels, but the other two involved transition substitutions. Phylogenetic analysis showed that the two nasopharyngeal strains in the present study were most closely related to the strains PDCoV/CHJXNI2/2015 from Jiangxi, China, and CH/Sichuan/S27/2012 from Sichuan, China. The outbreak strains in the United States possessed highly similar genome sequences and were clustered monophyletically, whereas the Asian strains were more diverse and paraphyletic. The detection of Coronavirus HKU15 in respiratory tracts of pigs implies that in addition to enteric infections, Coronavirus HKU15 may be able to cause respiratory infections in pigs and that in addition to fecal-oral transmission, the virus could possibly spread through the respiratory route. The presence of the virus in respiratory samples provides an alternative clinical sample to confirm the diagnosis of Coronavirus HKU15 infection. Quasispecies were unprecedentedly observed in the 5′-untranslated region of coronavirus genomes.",2017 Jun 21,"['Woo, Patrick CY', 'Lau, Susanna KP', 'Tsang, Chi-Ching', 'Lau, Candy CY', 'Wong, Po-Chun', 'Chow, Franklin WN', 'Fong, Jordan YH', 'Yuen, Kwok-Yung']",Emerg Microbes Infect,,,False
42625869758be2cf4fa4c991326f3f49c0a38bb2,PMC,Coronavirus HKU15 in respiratory tract of pigs and first discovery of coronavirus quasispecies in 5′-untranslated region,http://dx.doi.org/10.1038/emi.2017.37,PMC5584481,28634353,CC BY,"Coronavirus HKU15 is a deltacoronavirus that was discovered in fecal samples of pigs in Hong Kong in 2012. Over the past three years, Coronavirus HKU15 has been widely detected in pigs in East/Southeast Asia and North America and has been associated with fatal outbreaks. In all such epidemiological studies, the virus was generally only detected in fecal/intestinal samples. In this molecular epidemiology study, we detected Coronavirus HKU15 in 9.6% of the nasopharyngeal samples obtained from 249 pigs in Hong Kong. Samples that tested positive were mostly collected during winter. Complete genome sequencing of the Coronavirus HKU15 in two nasopharyngeal samples revealed quasispecies in one of the samples. Two of the polymorphic sites involved indels, but the other two involved transition substitutions. Phylogenetic analysis showed that the two nasopharyngeal strains in the present study were most closely related to the strains PDCoV/CHJXNI2/2015 from Jiangxi, China, and CH/Sichuan/S27/2012 from Sichuan, China. The outbreak strains in the United States possessed highly similar genome sequences and were clustered monophyletically, whereas the Asian strains were more diverse and paraphyletic. The detection of Coronavirus HKU15 in respiratory tracts of pigs implies that in addition to enteric infections, Coronavirus HKU15 may be able to cause respiratory infections in pigs and that in addition to fecal-oral transmission, the virus could possibly spread through the respiratory route. The presence of the virus in respiratory samples provides an alternative clinical sample to confirm the diagnosis of Coronavirus HKU15 infection. Quasispecies were unprecedentedly observed in the 5′-untranslated region of coronavirus genomes.",2017 Jun 21,"['Woo, Patrick CY', 'Lau, Susanna KP', 'Tsang, Chi-Ching', 'Lau, Candy CY', 'Wong, Po-Chun', 'Chow, Franklin WN', 'Fong, Jordan YH', 'Yuen, Kwok-Yung']",Emerg Microbes Infect,,,False
2dcb2c53f12e45bb92c07e5b47d82dbe495bede9,PMC,Mapping infectious disease hospital surge threats to lessons learnt in Singapore: a systems analysis and development of a framework to inform how to DECIDE on planning and response strategies,http://dx.doi.org/10.1186/s12913-017-2552-1,PMC5584534,28870193,CC BY,"BACKGROUND: Hospital usage and service demand during an Infectious Disease (ID) outbreak can tax the health system in different ways. Herein we conceptualize hospital surge elements, and lessons learnt from such events, to help build appropriately matched responses to future ID surge threats. METHODS: We used the Interpretive Descriptive qualitative approach. Interviews (n = 35) were conducted with governance and public health specialists; hospital based staff; and General Practitioners. Key policy literature in tandem with the interview data were used to iteratively generate a Hospital ID Surge framework. We anchored our narrative account within this framework, which is used to structure our analysis. RESULTS: A spectrum of surge threats from combinations of capacity (for crowding) and capability (for treatment complexity) demands were identified. Starting with the Pyramid scenario, or an influx of high screening rates flooding Emergency Departments, alongside fewer and manageable admissions; the Reverse-Pyramid occurs when few cases are screened and admitted but those that are, are complex; during a ‘Black’ scenario, the system is overburdened by both crowding and complexity. The Singapore hospital system is highly adapted to crowding, functioning remarkably well at constant near-full capacity in Peacetime and resilient to Endemic surges. We catalogue 26 strategies from lessons learnt relating to staffing, space, supplies and systems, crystalizing institutional memory. The DECIDE model advocates linking these strategies to types of surge threats and offers a step-by-step guide for coordinating outbreak planning and response. CONCLUSIONS: Lack of a shared definition and decision making of surge threats had rendered the procedures somewhat duplicative. This burden was paradoxically exacerbated by a health system that highly prizes planning and forward thinking, but worked largely in silo until an ID crisis hit. Many such lessons can be put into play to further strengthen our current hospital governance and adapted to more diverse settings.",2017 Sep 4,"['Singh, Shweta R.', 'Coker, Richard', 'Vrijhoef, Hubertus J-M', 'Leo, Yee Sin', 'Chow, Angela', 'Lim, Poh Lian', 'Tan, Qinghui', 'Chen, Mark I-Cheng', 'Hildon, Zoe Jane-Lara']",BMC Health Serv Res,,,True
8a00f7c5a0cfb0b083ba29ea141ddb78e942b6aa,PMC,"Maoto, a Traditional Japanese Herbal Medicine, Inhibits Uncoating of Influenza Virus",http://dx.doi.org/10.1155/2017/1062065,PMC5585631,28904550,CC BY,"We previously reported in randomized controlled trials that maoto, a traditional herbal medicine, showed clinical and virological efficacy for seasonal influenza. In this study, a culturing system for influenza was used to test the effect of maoto. A549 cells in the culture were infected with influenza virus A (PR8) and followed after treatment with maoto; the virus titers in the culture supernatant, intracellular viral proteins, and viral RNA were determined. When infected cells were cultured with maoto for 24 hr, the virus titer and protein were significantly reduced compared with medium only. Other subtypes, A/H3N2, H1N1pdm, and B, were also inhibited by maoto. Proliferation of viral RNA in a 6 hr culture was inhibited by maoto in the early phase, especially in the first 30 min. Focusing on the entry step of the influenza virus, we found that endosomal pH, regulated by vacuolar-type H(+) ATPase (V-ATPase) located in the membrane, was increased when treated with maoto. We also found that uncoating of influenza viruses was also inhibited by maoto, resulting in the increase of the number of virus particles in endosomes. These results strongly suggest that the inhibition of endosomal acidification by maoto results in blocking influenza virus entry to cytoplasm, probably through the inhibition of V-ATPase. The present study provides evidence that supports the clinical use of maoto for the treatment of influenza.",2017 Aug 22,"['Masui, Shinta', 'Nabeshima, Shigeki', 'Ajisaka, Kazuhiko', 'Yamauchi, Kei', 'Itoh, Ryota', 'Ishii, Kazunari', 'Soejima, Toshinori', 'Hiromatsu, Kenji']",Evid Based Complement Alternat Med,,,True
56deda06e91099aef48cd57fde743be79523f164,PMC,The porcine virome and xenotransplantation,http://dx.doi.org/10.1186/s12985-017-0836-z,PMC5585927,28874166,CC BY,"The composition of the porcine virome includes viruses that infect pig cells, ancient virus-derived elements including endogenous retroviruses inserted in the pig chromosomes, and bacteriophages that infect a broad array of bacteria that inhabit pigs. Viruses infecting pigs, among them viruses also infecting human cells, as well as porcine endogenous retroviruses (PERVs) are of importance when evaluating the virus safety of xenotransplantation. Bacteriophages associated with bacteria mainly in the gut are not relevant in this context. Xenotransplantation using pig cells, tissues or organs is under development in order to alleviate the shortage of human transplants. Here for the first time published data describing the viromes in different pigs and their relevance for the virus safety of xenotransplantation is analysed. In conclusion, the analysis of the porcine virome has resulted in numerous new viruses being described, although their impact on xenotransplantation is unclear. Most importantly, viruses with known or suspected zoonotic potential were often not detected by next generation sequencing, but were revealed by more sensitive methods.",2017 Sep 6,"Denner, Joachim",Virol J,,,True
05186884eb6aed574507e7f0f9316375ffbc6494,PMC,Secretome of Intestinal Bacilli: A Natural Guard against Pathologies,http://dx.doi.org/10.3389/fmicb.2017.01666,PMC5586196,28919884,CC BY,"Current studies of human gut microbiome usually do not consider the special functional role of transient microbiota, although some of its members remain in the host for a long time and produce broad spectrum of biologically active substances. Getting into the gastrointestinal tract (GIT) with food, water and probiotic preparations, two representatives of Bacilli class, genera Bacillus and Lactobacillus, colonize epithelium blurring the boundaries between resident and transient microbiota. Despite their minor proportion in the microbiome composition, these bacteria can significantly affect both the intestinal microbiota and the entire body thanks to a wide range of secreted compounds. Recently, insufficiency and limitations of pure genome-based analysis of gut microbiota became known. Thus, the need for intense functional studies is evident. This review aims to characterize the Bacillus and Lactobacillus in GIT, as well as the functional roles of the components released by these members of microbial intestinal community. Complex of their secreted compounds is referred by us as the “bacillary secretome.” The composition of the bacillary secretome, its biological effects in GIT and role in counteraction to infectious diseases and oncological pathologies in human organism is the subject of the review.",2017 Sep 1,"['Ilinskaya, Olga N.', 'Ulyanova, Vera V.', 'Yarullina, Dina R.', 'Gataullin, Ilgiz G.']",Front Microbiol,,,True
416266511be0451304064a125f0bcf108c56f375,PMC,A system dynamics approach to understanding the One Health concept,http://dx.doi.org/10.1371/journal.pone.0184430,PMC5587294,28877267,CC BY,"There have been many terms used to describe the One Health concept, including movement, strategy, framework, agenda, approach, among others. However, the inter-relationships of the disciplines engaged in the One Health concept have not been well described. To identify and better elucidate the internal feedback mechanisms of One Health, we employed a system dynamics approach. First, a systematic literature review was conducted via searches in PubMed, Web of Knowledge, and ProQuest with the search terms: ‘One Health’ and (concept* or approach*). In addition, we used the HistCite(®) tool to add significant articles on One Health to the library. Then, of the 2368 articles identified, 19 were selected for evaluating the inter-relationships of disciplines engaged in One Health. Herein, we report a visually rich, theoretical model regarding interactions of various disciplines and complex problem descriptors engaged in One Health problem solving. This report provides a conceptual framework for future descriptions of the interdisciplinary engagements involved in One Health.",2017 Sep 6,"['Xie, Tai', 'Liu, Wenbao', 'Anderson, Benjamin D.', 'Liu, Xiaorong', 'Gray, Gregory C.']",PLoS One,,,True
d9830dd1a44317a284afc206daa20206fa6552bc,PMC,A system dynamics approach to understanding the One Health concept,http://dx.doi.org/10.1371/journal.pone.0184430,PMC5587294,28877267,CC BY,"There have been many terms used to describe the One Health concept, including movement, strategy, framework, agenda, approach, among others. However, the inter-relationships of the disciplines engaged in the One Health concept have not been well described. To identify and better elucidate the internal feedback mechanisms of One Health, we employed a system dynamics approach. First, a systematic literature review was conducted via searches in PubMed, Web of Knowledge, and ProQuest with the search terms: ‘One Health’ and (concept* or approach*). In addition, we used the HistCite(®) tool to add significant articles on One Health to the library. Then, of the 2368 articles identified, 19 were selected for evaluating the inter-relationships of disciplines engaged in One Health. Herein, we report a visually rich, theoretical model regarding interactions of various disciplines and complex problem descriptors engaged in One Health problem solving. This report provides a conceptual framework for future descriptions of the interdisciplinary engagements involved in One Health.",2017 Sep 6,"['Xie, Tai', 'Liu, Wenbao', 'Anderson, Benjamin D.', 'Liu, Xiaorong', 'Gray, Gregory C.']",PLoS One,,,True
95c03885392135d1ba49d3db5480fd91750e5b73,PMC,Genetic and antigenic characterization of influenza A(H3N2) in Cameroon during the 2014-2016 influenza seasons,http://dx.doi.org/10.1371/journal.pone.0184411,PMC5587321,28877235,CC BY,"The first outbreak of influenza A(H3N2) occurred in 1968 and caused the third flu pandemic of the 20(th) century. It has affected multiple countries over time. The best strategy to reduce the burden of influenza is through vaccination whose efficacy varies with respect to the circulating strains. This study was performed to better understand the molecular evolution of influenza A(H3N2) and assess vaccine efficacy in Cameroon. Complete sequences of three gene segments were obtained from 2014 to 2016 influenza seasons in Cameroon. Hemagglutinin (HA), Neuraminidase (NA) and matrix (M) genes of 35 A(H3N2) virus strains were amplified and sequenced. Predicted vaccine efficacy was measured using the P(epitope) model. Phylogenetic analysis of the HA gene showed that all Cameroonian strains had evolved away from the 3C.1-A/Texas/50/2012-like clade. Globally, 2014 virus strains clustered with the 2015–2016 vaccine strain, 3C.3a-A/Switzerland/9715293/2013, whereas 2015 and 2016 virus strains clustered with the 2016–2017 vaccine strain, 3C.2a-A/HongKong/4801/2014. In order to determine the genotypic drug susceptibility to neuraminidase inhibitors and amantadine, the NA and M2 protein coding sequences were analyzed. There was no strain with characteristic mutation for resistance to neuraminidase inhibitors, per contra; all strains possessed the substitution S31N, peculiar of resistance to adamantanes. There was drift in influenza A(H3N2) dominant epitopes B (2014 and 2015) to epitopes A (2016) with a theoretical efficiency in vaccine ranging from low to moderate. The presence of several antigenic site mutations among H3N2 virus strains between 2014–2016 influenza seasons in Cameroon confirms the progressing evolution of circulating H3N2 strains.",2017 Sep 6,"['Monamele, Gwladys C.', 'Vernet, Marie-Astrid', 'Njankouo, Mohammed R.', 'Victoir, Kathleen', 'Akoachere, Jane Francis', 'Anong, Damian', 'Njouom, Richard']",PLoS One,,,True
39597549aac294e1fd905161548e59b7989af01e,PMC,Genetic and antigenic characterization of influenza A(H3N2) in Cameroon during the 2014-2016 influenza seasons,http://dx.doi.org/10.1371/journal.pone.0184411,PMC5587321,28877235,CC BY,"The first outbreak of influenza A(H3N2) occurred in 1968 and caused the third flu pandemic of the 20(th) century. It has affected multiple countries over time. The best strategy to reduce the burden of influenza is through vaccination whose efficacy varies with respect to the circulating strains. This study was performed to better understand the molecular evolution of influenza A(H3N2) and assess vaccine efficacy in Cameroon. Complete sequences of three gene segments were obtained from 2014 to 2016 influenza seasons in Cameroon. Hemagglutinin (HA), Neuraminidase (NA) and matrix (M) genes of 35 A(H3N2) virus strains were amplified and sequenced. Predicted vaccine efficacy was measured using the P(epitope) model. Phylogenetic analysis of the HA gene showed that all Cameroonian strains had evolved away from the 3C.1-A/Texas/50/2012-like clade. Globally, 2014 virus strains clustered with the 2015–2016 vaccine strain, 3C.3a-A/Switzerland/9715293/2013, whereas 2015 and 2016 virus strains clustered with the 2016–2017 vaccine strain, 3C.2a-A/HongKong/4801/2014. In order to determine the genotypic drug susceptibility to neuraminidase inhibitors and amantadine, the NA and M2 protein coding sequences were analyzed. There was no strain with characteristic mutation for resistance to neuraminidase inhibitors, per contra; all strains possessed the substitution S31N, peculiar of resistance to adamantanes. There was drift in influenza A(H3N2) dominant epitopes B (2014 and 2015) to epitopes A (2016) with a theoretical efficiency in vaccine ranging from low to moderate. The presence of several antigenic site mutations among H3N2 virus strains between 2014–2016 influenza seasons in Cameroon confirms the progressing evolution of circulating H3N2 strains.",2017 Sep 6,"['Monamele, Gwladys C.', 'Vernet, Marie-Astrid', 'Njankouo, Mohammed R.', 'Victoir, Kathleen', 'Akoachere, Jane Francis', 'Anong, Damian', 'Njouom, Richard']",PLoS One,,,False
88982eb12bc4a2a4465ff51976c8d2f22a9838e9,PMC,Genetic and antigenic characterization of influenza A(H3N2) in Cameroon during the 2014-2016 influenza seasons,http://dx.doi.org/10.1371/journal.pone.0184411,PMC5587321,28877235,CC BY,"The first outbreak of influenza A(H3N2) occurred in 1968 and caused the third flu pandemic of the 20(th) century. It has affected multiple countries over time. The best strategy to reduce the burden of influenza is through vaccination whose efficacy varies with respect to the circulating strains. This study was performed to better understand the molecular evolution of influenza A(H3N2) and assess vaccine efficacy in Cameroon. Complete sequences of three gene segments were obtained from 2014 to 2016 influenza seasons in Cameroon. Hemagglutinin (HA), Neuraminidase (NA) and matrix (M) genes of 35 A(H3N2) virus strains were amplified and sequenced. Predicted vaccine efficacy was measured using the P(epitope) model. Phylogenetic analysis of the HA gene showed that all Cameroonian strains had evolved away from the 3C.1-A/Texas/50/2012-like clade. Globally, 2014 virus strains clustered with the 2015–2016 vaccine strain, 3C.3a-A/Switzerland/9715293/2013, whereas 2015 and 2016 virus strains clustered with the 2016–2017 vaccine strain, 3C.2a-A/HongKong/4801/2014. In order to determine the genotypic drug susceptibility to neuraminidase inhibitors and amantadine, the NA and M2 protein coding sequences were analyzed. There was no strain with characteristic mutation for resistance to neuraminidase inhibitors, per contra; all strains possessed the substitution S31N, peculiar of resistance to adamantanes. There was drift in influenza A(H3N2) dominant epitopes B (2014 and 2015) to epitopes A (2016) with a theoretical efficiency in vaccine ranging from low to moderate. The presence of several antigenic site mutations among H3N2 virus strains between 2014–2016 influenza seasons in Cameroon confirms the progressing evolution of circulating H3N2 strains.",2017 Sep 6,"['Monamele, Gwladys C.', 'Vernet, Marie-Astrid', 'Njankouo, Mohammed R.', 'Victoir, Kathleen', 'Akoachere, Jane Francis', 'Anong, Damian', 'Njouom, Richard']",PLoS One,,,False
442c4cc45848e962be501bd21f5484df9d547ce1,PMC,Regional genetic diversity for NNV grouper viruses across the Indo-Asian region – implications for selecting virus resistance in farmed groupers,http://dx.doi.org/10.1038/s41598-017-11263-4,PMC5587679,28878324,CC BY,"Grouper aquaculture around Asia is impacted by the nervous necrosis virus (NNV) and, in response, host resistance to this infection is being considered as a trait for selection. However efficient selection may be confounded if there are different genetic strains of NNV within and between regions and over years. This study uses statistical approaches and assessment of “characteristic attributes” (i.e. nucleotide positions that discriminate among strains) to assess whether published and new NNV RNA2 cds sequences show genetic differentiation over geography, host species and years. Rather clear evidence was found for regional strains of NNV. Interestingly, most of the geographic defining “characteristic attributes” were in codon position three, and not translated into differences for the protein capsid (i.e. they were synonymous variations), suggesting that while NNV strains were geographically isolated and had diverged in different regions for RNA sequences, selection had largely conserved the protein sequences among regions. The apparent selection constraint on the capsid protein may mitigate the risk that despite geographic subdivision, NNV strain variability will confound genetic selection for host resistance. The existence of regional Asian NNV strains may suggest that hatcheries are at risk from NNV not only from imported material but also from endemic reservoirs.",2017 Sep 6,"['Knibb, Wayne', 'Luu, Giang', 'Premachandra, H. K. A.', 'Lu, Ming-Wei', 'Nguyen, Nguyen Hong']",Sci Rep,,,True
ca678602a715c23201b3947824b05053b0f56c4d,PMC,Distribution of O-Acetylated Sialic Acids among Target Host Tissues for Influenza Virus,http://dx.doi.org/10.1128/mSphere.00379-16,PMC5588038,28904995,CC BY,"Sialic acids (Sias) are important glycans displayed on the cells and tissues of many different animals and are frequent targets for binding and modification by pathogens, including influenza viruses. Influenza virus hemagglutinins bind Sias during the infection of their normal hosts, while the encoded neuraminidases and/or esterases remove or modify the Sia to allow virion release or to prevent rebinding. Sias naturally occur in a variety of modified forms, and modified Sias can alter influenza virus host tropisms through their altered interactions with the viral glycoproteins. However, the distribution of modified Sia forms and their effects on pathogen-host interactions are still poorly understood. Here we used probes developed from viral Sia-binding proteins to detect O-acetylated (4-O-acetyl, 9-O-acetyl, and 7,9-O-acetyl) Sias displayed on the tissues of some natural or experimental hosts for influenza viruses. These modified Sias showed highly variable displays between the hosts and tissues examined. The 9-O-acetyl (and 7,9-) modified Sia forms were found on cells and tissues of many hosts, including mice, humans, ferrets, guinea pigs, pigs, horses, dogs, as well as in those of ducks and embryonated chicken egg tissues and membranes, although in variable amounts. The 4-O-acetyl Sias were found in the respiratory tissues of fewer animals, being primarily displayed in the horse and guinea pig, but were not detected in humans or pigs. The results suggest that these Sia variants may influence virus tropisms by altering and selecting their cell interactions. IMPORTANCE Sialic acids (Sias) are key glycans that control or modulate many normal cell and tissue functions while also interacting with a variety of pathogens, including many different viruses. Sias are naturally displayed in a variety of different forms, with modifications at several positions that can alter their functional interactions with pathogens. In addition, Sias are often modified or removed by enzymes such as host or pathogen esterases or sialidases (neuraminidases), and Sia modifications can alter those enzymatic activities to impact pathogen infections. Sia chemical diversity in different hosts and tissues likely alters the pathogen-host interactions and influences the outcome of infection. Here we explored the display of 4-O-acetyl, 9-O-acetyl, and 7,9-O-acetyl modified Sia forms in some target tissues for influenza virus infection in mice, humans, birds, guinea pigs, ferrets, swine, horses, and dogs, which encompass many natural and laboratory hosts of those viruses.",2017 Sep 6,"['Wasik, Brian R.', 'Barnard, Karen N.', 'Ossiboff, Robert J.', 'Khedri, Zahra', 'Feng, Kurtis H.', 'Yu, Hai', 'Chen, Xi', 'Perez, Daniel R.', 'Varki, Ajit', 'Parrish, Colin R.']",mSphere,,,True
df753ddb66629cfd0795d0ffa319caa0440de284,PMC,The use of a P. falciparum specific coiled-coil domain to construct a self-assembling protein nanoparticle vaccine to prevent malaria,http://dx.doi.org/10.1186/s12951-017-0295-0,PMC5588597,28877692,CC BY,"BACKGROUND: The parasitic disease malaria remains a major global public health concern and no truly effective vaccine exists. One approach to the development of a malaria vaccine is to target the asexual blood stage that results in clinical symptoms. Most attempts have failed. New antigens such as P27A and P27 have emerged as potential new vaccine candidates. Multiple studies have demonstrated that antigens are more immunogenic and are better correlated with protection when presented on particulate delivery systems. One such particulate delivery system is the self-assembling protein nanoparticle (SAPN) that relies on coiled-coil domains of proteins to form stable nanoparticles. In the past we have used de novo designed amino acid domains to drive the formation of the coiled-coil scaffolds which present the antigenic epitopes on the particle surface. RESULTS: Here we use naturally occurring domains found in the tex1 protein to form the coiled-coil scaffolding of the nanoparticle. Thus, by engineering P27A and a new extended form of the coiled-coil domain P27 onto the N and C terminus of the SAPN protein monomer we have developed a particulate delivery system that effectively displays both antigens on a single particle that uses malaria tex1 sequences to form the nanoparticle scaffold. These particles are immunogenic in a murine model and induce immune responses similar to the ones observed in seropositive individuals in malaria endemic regions. CONCLUSIONS: We demonstrate that our P27/P27A-SAPNs induce an immune response akin to the one in seropositive individuals in Burkina Faso. Since P27 is highly conserved among different Plasmodium species, these novel SAPNs may even provide cross-protection between Plasmodium falciparum and Plasmodium vivax the two major human malaria pathogens. As the SAPNs are also easy to manufacture and store they can be delivered to the population in need without complication thus providing a low cost malaria vaccine.",2017 Sep 6,"['Karch, Christopher P.', 'Doll, Tais A. P. F.', 'Paulillo, Sara M.', 'Nebie, Issa', 'Lanar, David E.', 'Corradin, Giampietro', 'Burkhard, Peter']",J Nanobiotechnology,,,True
465fdc27c98bca041c61f4c5d85671ec92a3b53d,PMC,Prediction of endoplasmic reticulum resident proteins using fragmented amino acid composition and support vector machine,http://dx.doi.org/10.7717/peerj.3561,PMC5588793,28890846,CC BY,"BACKGROUND: The endoplasmic reticulum plays an important role in many cellular processes, which includes protein synthesis, folding and post-translational processing of newly synthesized proteins. It is also the site for quality control of misfolded proteins and entry point of extracellular proteins to the secretory pathway. Hence at any given point of time, endoplasmic reticulum contains two different cohorts of proteins, (i) proteins involved in endoplasmic reticulum-specific function, which reside in the lumen of the endoplasmic reticulum, called as endoplasmic reticulum resident proteins and (ii) proteins which are in process of moving to the extracellular space. Thus, endoplasmic reticulum resident proteins must somehow be distinguished from newly synthesized secretory proteins, which pass through the endoplasmic reticulum on their way out of the cell. Approximately only 50% of the proteins used in this study as training data had endoplasmic reticulum retention signal, which shows that these signals are not essentially present in all endoplasmic reticulum resident proteins. This also strongly indicates the role of additional factors in retention of endoplasmic reticulum-specific proteins inside the endoplasmic reticulum. METHODS: This is a support vector machine based method, where we had used different forms of protein features as inputs for support vector machine to develop the prediction models. During training leave-one-out approach of cross-validation was used. Maximum performance was obtained with a combination of amino acid compositions of different part of proteins. RESULTS: In this study, we have reported a novel support vector machine based method for predicting endoplasmic reticulum resident proteins, named as ERPred. During training we achieved a maximum accuracy of 81.42% with leave-one-out approach of cross-validation. When evaluated on independent dataset, ERPred did prediction with sensitivity of 72.31% and specificity of 83.69%. We have also annotated six different proteomes to predict the candidate endoplasmic reticulum resident proteins in them. A webserver, ERPred, was developed to make the method available to the scientific community, which can be accessed at http://proteininformatics.org/mkumar/erpred/index.html. DISCUSSION: We found that out of 124 proteins of the training dataset, only 66 proteins had endoplasmic reticulum retention signals, which shows that these signals are not an absolute necessity for endoplasmic reticulum resident proteins to remain inside the endoplasmic reticulum. This observation also strongly indicates the role of additional factors in retention of proteins inside the endoplasmic reticulum. Our proposed predictor, ERPred, is a signal independent tool. It is tuned for the prediction of endoplasmic reticulum resident proteins, even if the query protein does not contain specific ER-retention signal.",2017 Sep 4,"['Kumar, Ravindra', 'Kumari, Bandana', 'Kumar, Manish']",PeerJ,,,True
c39dd28fc793a6826ea646a27b79cdf565a42cde,PMC,"Think globally, act locally: Phylodynamic reconstruction of infectious bronchitis virus (IBV) QX genotype (GI-19 lineage) reveals different population dynamics and spreading patterns when evaluated on different epidemiological scales",http://dx.doi.org/10.1371/journal.pone.0184401,PMC5589226,28880958,CC BY,"Infectious bronchitis virus (IBV) represents one of the poultry industry major threats, particularly in high density producing countries. The emergence and spread of new IBV genotypes have frustrated the various disease control efforts implemented over time. Despite that, few comprehensive and large scale studies have been performed to understand the international and local spreading dynamics of this virus. In the present work, these phenomena were evaluated by implementing a Bayesian phylodynamic approach to reconstruct the epidemiological patterns and population history of the QX genotype (currently renamed GI-19 lineage), the most relevant IBV lineage of the Old-World. Our analysis, based on 807 partial S1 sequences of strains collected from 18 countries between 1993 and 2015, demonstrates that this genotype originated in China well before its first identification. After a prolonged local circulation, it started spreading to other European, Asian and Middle East countries in successive waves, which were mirrored by concomitant fluctuations in viral population size. Interestingly, the within-Europe spread was characterized by a higher estimated migration rate compared with the inter-continental one, potentially reflecting the closer geographic and economic relationships among these countries. Nevertheless, the colonization of new states by the GI-19 lineage appeared to occur mostly by single introduction events in both intra and inter-continental spread, likely because of epidemiological factor and health policy combination which seems to prevent the frequent introduction and mixing of different strains. On the other hand, the within Italy QX circulation reconstruction showed a much more intricate connection network among different locations, evidencing the difficulty in controlling IBV spread especially in highly densely poultry populated areas. The presence of several well supported epidemiological links among distantly related Italian regions testifies that animal transportation and indirect transmission routes rather than local airborne diffusion contribute to the QX success and persistence at local scale. Globally, the spreading dynamics and evolution of the QX genotype were reconstructed from its very origin to nowadays, demonstrating the need of more effective direct control measures, particularly within each country. Unfortunately, the incompleteness of available molecular epidemiology data represents an insurmountable limit which leaves many questions currently unsolved, thus highlighting the compulsoriness of a structured monitoring and data sharing system implementation.",2017 Sep 7,"['Franzo, Giovanni', 'Massi, Paola', 'Tucciarone, Claudia Maria', 'Barbieri, Ilaria', 'Tosi, Giovanni', 'Fiorentini, Laura', 'Ciccozzi, Massimo', 'Lavazza, Antonio', 'Cecchinato, Mattia', 'Moreno, Ana']",PLoS One,,,True
f4f1e654ae521b0736313f3b93fe498ae8d4ea0e,PMC,"Think globally, act locally: Phylodynamic reconstruction of infectious bronchitis virus (IBV) QX genotype (GI-19 lineage) reveals different population dynamics and spreading patterns when evaluated on different epidemiological scales",http://dx.doi.org/10.1371/journal.pone.0184401,PMC5589226,28880958,CC BY,"Infectious bronchitis virus (IBV) represents one of the poultry industry major threats, particularly in high density producing countries. The emergence and spread of new IBV genotypes have frustrated the various disease control efforts implemented over time. Despite that, few comprehensive and large scale studies have been performed to understand the international and local spreading dynamics of this virus. In the present work, these phenomena were evaluated by implementing a Bayesian phylodynamic approach to reconstruct the epidemiological patterns and population history of the QX genotype (currently renamed GI-19 lineage), the most relevant IBV lineage of the Old-World. Our analysis, based on 807 partial S1 sequences of strains collected from 18 countries between 1993 and 2015, demonstrates that this genotype originated in China well before its first identification. After a prolonged local circulation, it started spreading to other European, Asian and Middle East countries in successive waves, which were mirrored by concomitant fluctuations in viral population size. Interestingly, the within-Europe spread was characterized by a higher estimated migration rate compared with the inter-continental one, potentially reflecting the closer geographic and economic relationships among these countries. Nevertheless, the colonization of new states by the GI-19 lineage appeared to occur mostly by single introduction events in both intra and inter-continental spread, likely because of epidemiological factor and health policy combination which seems to prevent the frequent introduction and mixing of different strains. On the other hand, the within Italy QX circulation reconstruction showed a much more intricate connection network among different locations, evidencing the difficulty in controlling IBV spread especially in highly densely poultry populated areas. The presence of several well supported epidemiological links among distantly related Italian regions testifies that animal transportation and indirect transmission routes rather than local airborne diffusion contribute to the QX success and persistence at local scale. Globally, the spreading dynamics and evolution of the QX genotype were reconstructed from its very origin to nowadays, demonstrating the need of more effective direct control measures, particularly within each country. Unfortunately, the incompleteness of available molecular epidemiology data represents an insurmountable limit which leaves many questions currently unsolved, thus highlighting the compulsoriness of a structured monitoring and data sharing system implementation.",2017 Sep 7,"['Franzo, Giovanni', 'Massi, Paola', 'Tucciarone, Claudia Maria', 'Barbieri, Ilaria', 'Tosi, Giovanni', 'Fiorentini, Laura', 'Ciccozzi, Massimo', 'Lavazza, Antonio', 'Cecchinato, Mattia', 'Moreno, Ana']",PLoS One,,,False
a4f090140598d8e46cc98e3e654a93d48bf5cec2,PMC,"Think globally, act locally: Phylodynamic reconstruction of infectious bronchitis virus (IBV) QX genotype (GI-19 lineage) reveals different population dynamics and spreading patterns when evaluated on different epidemiological scales",http://dx.doi.org/10.1371/journal.pone.0184401,PMC5589226,28880958,CC BY,"Infectious bronchitis virus (IBV) represents one of the poultry industry major threats, particularly in high density producing countries. The emergence and spread of new IBV genotypes have frustrated the various disease control efforts implemented over time. Despite that, few comprehensive and large scale studies have been performed to understand the international and local spreading dynamics of this virus. In the present work, these phenomena were evaluated by implementing a Bayesian phylodynamic approach to reconstruct the epidemiological patterns and population history of the QX genotype (currently renamed GI-19 lineage), the most relevant IBV lineage of the Old-World. Our analysis, based on 807 partial S1 sequences of strains collected from 18 countries between 1993 and 2015, demonstrates that this genotype originated in China well before its first identification. After a prolonged local circulation, it started spreading to other European, Asian and Middle East countries in successive waves, which were mirrored by concomitant fluctuations in viral population size. Interestingly, the within-Europe spread was characterized by a higher estimated migration rate compared with the inter-continental one, potentially reflecting the closer geographic and economic relationships among these countries. Nevertheless, the colonization of new states by the GI-19 lineage appeared to occur mostly by single introduction events in both intra and inter-continental spread, likely because of epidemiological factor and health policy combination which seems to prevent the frequent introduction and mixing of different strains. On the other hand, the within Italy QX circulation reconstruction showed a much more intricate connection network among different locations, evidencing the difficulty in controlling IBV spread especially in highly densely poultry populated areas. The presence of several well supported epidemiological links among distantly related Italian regions testifies that animal transportation and indirect transmission routes rather than local airborne diffusion contribute to the QX success and persistence at local scale. Globally, the spreading dynamics and evolution of the QX genotype were reconstructed from its very origin to nowadays, demonstrating the need of more effective direct control measures, particularly within each country. Unfortunately, the incompleteness of available molecular epidemiology data represents an insurmountable limit which leaves many questions currently unsolved, thus highlighting the compulsoriness of a structured monitoring and data sharing system implementation.",2017 Sep 7,"['Franzo, Giovanni', 'Massi, Paola', 'Tucciarone, Claudia Maria', 'Barbieri, Ilaria', 'Tosi, Giovanni', 'Fiorentini, Laura', 'Ciccozzi, Massimo', 'Lavazza, Antonio', 'Cecchinato, Mattia', 'Moreno, Ana']",PLoS One,,,False
4f1332e0f453c2e831a9bc7fd40b75a02029c20d,PMC,"Think globally, act locally: Phylodynamic reconstruction of infectious bronchitis virus (IBV) QX genotype (GI-19 lineage) reveals different population dynamics and spreading patterns when evaluated on different epidemiological scales",http://dx.doi.org/10.1371/journal.pone.0184401,PMC5589226,28880958,CC BY,"Infectious bronchitis virus (IBV) represents one of the poultry industry major threats, particularly in high density producing countries. The emergence and spread of new IBV genotypes have frustrated the various disease control efforts implemented over time. Despite that, few comprehensive and large scale studies have been performed to understand the international and local spreading dynamics of this virus. In the present work, these phenomena were evaluated by implementing a Bayesian phylodynamic approach to reconstruct the epidemiological patterns and population history of the QX genotype (currently renamed GI-19 lineage), the most relevant IBV lineage of the Old-World. Our analysis, based on 807 partial S1 sequences of strains collected from 18 countries between 1993 and 2015, demonstrates that this genotype originated in China well before its first identification. After a prolonged local circulation, it started spreading to other European, Asian and Middle East countries in successive waves, which were mirrored by concomitant fluctuations in viral population size. Interestingly, the within-Europe spread was characterized by a higher estimated migration rate compared with the inter-continental one, potentially reflecting the closer geographic and economic relationships among these countries. Nevertheless, the colonization of new states by the GI-19 lineage appeared to occur mostly by single introduction events in both intra and inter-continental spread, likely because of epidemiological factor and health policy combination which seems to prevent the frequent introduction and mixing of different strains. On the other hand, the within Italy QX circulation reconstruction showed a much more intricate connection network among different locations, evidencing the difficulty in controlling IBV spread especially in highly densely poultry populated areas. The presence of several well supported epidemiological links among distantly related Italian regions testifies that animal transportation and indirect transmission routes rather than local airborne diffusion contribute to the QX success and persistence at local scale. Globally, the spreading dynamics and evolution of the QX genotype were reconstructed from its very origin to nowadays, demonstrating the need of more effective direct control measures, particularly within each country. Unfortunately, the incompleteness of available molecular epidemiology data represents an insurmountable limit which leaves many questions currently unsolved, thus highlighting the compulsoriness of a structured monitoring and data sharing system implementation.",2017 Sep 7,"['Franzo, Giovanni', 'Massi, Paola', 'Tucciarone, Claudia Maria', 'Barbieri, Ilaria', 'Tosi, Giovanni', 'Fiorentini, Laura', 'Ciccozzi, Massimo', 'Lavazza, Antonio', 'Cecchinato, Mattia', 'Moreno, Ana']",PLoS One,,,False
09349b2b8775baedb71ab7232c332242c5c39f68,PMC,"Think globally, act locally: Phylodynamic reconstruction of infectious bronchitis virus (IBV) QX genotype (GI-19 lineage) reveals different population dynamics and spreading patterns when evaluated on different epidemiological scales",http://dx.doi.org/10.1371/journal.pone.0184401,PMC5589226,28880958,CC BY,"Infectious bronchitis virus (IBV) represents one of the poultry industry major threats, particularly in high density producing countries. The emergence and spread of new IBV genotypes have frustrated the various disease control efforts implemented over time. Despite that, few comprehensive and large scale studies have been performed to understand the international and local spreading dynamics of this virus. In the present work, these phenomena were evaluated by implementing a Bayesian phylodynamic approach to reconstruct the epidemiological patterns and population history of the QX genotype (currently renamed GI-19 lineage), the most relevant IBV lineage of the Old-World. Our analysis, based on 807 partial S1 sequences of strains collected from 18 countries between 1993 and 2015, demonstrates that this genotype originated in China well before its first identification. After a prolonged local circulation, it started spreading to other European, Asian and Middle East countries in successive waves, which were mirrored by concomitant fluctuations in viral population size. Interestingly, the within-Europe spread was characterized by a higher estimated migration rate compared with the inter-continental one, potentially reflecting the closer geographic and economic relationships among these countries. Nevertheless, the colonization of new states by the GI-19 lineage appeared to occur mostly by single introduction events in both intra and inter-continental spread, likely because of epidemiological factor and health policy combination which seems to prevent the frequent introduction and mixing of different strains. On the other hand, the within Italy QX circulation reconstruction showed a much more intricate connection network among different locations, evidencing the difficulty in controlling IBV spread especially in highly densely poultry populated areas. The presence of several well supported epidemiological links among distantly related Italian regions testifies that animal transportation and indirect transmission routes rather than local airborne diffusion contribute to the QX success and persistence at local scale. Globally, the spreading dynamics and evolution of the QX genotype were reconstructed from its very origin to nowadays, demonstrating the need of more effective direct control measures, particularly within each country. Unfortunately, the incompleteness of available molecular epidemiology data represents an insurmountable limit which leaves many questions currently unsolved, thus highlighting the compulsoriness of a structured monitoring and data sharing system implementation.",2017 Sep 7,"['Franzo, Giovanni', 'Massi, Paola', 'Tucciarone, Claudia Maria', 'Barbieri, Ilaria', 'Tosi, Giovanni', 'Fiorentini, Laura', 'Ciccozzi, Massimo', 'Lavazza, Antonio', 'Cecchinato, Mattia', 'Moreno, Ana']",PLoS One,,,False
08d822c186460651ee5f3a44d365b0701aff56e3,PMC,Nuclease escape elements protect messenger RNA against cleavage by multiple viral endonucleases,http://dx.doi.org/10.1371/journal.ppat.1006593,PMC5589255,28841715,CC BY,"During lytic Kaposi’s sarcoma-associated herpesvirus (KSHV) infection, the viral endonu- clease SOX promotes widespread degradation of cytoplasmic messenger RNA (mRNA). However, select mRNAs, including the transcript encoding interleukin-6 (IL-6), escape SOX-induced cleavage. IL-6 escape is mediated through a 3’ UTR RNA regulatory element that overrides the SOX targeting mechanism. Here, we reveal that this protective RNA element functions to broadly restrict cleavage by a range of homologous and non-homologous viral endonucleases. However, it does not impede cleavage by cellular endonucleases. The IL-6 protective sequence may be representative of a larger class of nuclease escape elements, as we identified a similar protective element in the GADD45B mRNA. The IL-6 and GADD45B-derived elements display similarities in their sequence, putative structure, and several associated RNA binding proteins. However, the overall composition of their ribonucleoprotein complexes appears distinct, leading to differences in the breadth of nucleases restricted. These findings highlight how RNA elements can selectively control transcript abundance in the background of widespread virus-induced mRNA degradation.",2017 Aug 25,"['Muller, Mandy', 'Glaunsinger, Britt A.']",PLoS Pathog,,,True
54e56ec5b95cb23c2b682b181bcc66b7fae8aa07,PMC,The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice,http://dx.doi.org/10.1371/journal.pone.0184568,PMC5589259,28880886,CC BY,"BRIL (bone-restricted IFITM-like), is a short transmembrane protein expressed almost exclusively in osteoblasts. Although much is known about its bone-restricted gene expression pattern and protein biochemical and topological features, little information is available for BRIL physiological function. Two autosomal dominant forms of osteogenesis imperfecta (OI) are caused by distinct, but recurrent mutations in the BRIL gene. Yet, the underlying mechanisms by which those mutations lead to OI are still poorly understood. A previous report indicated that BRIL knockout (KO) mice had bone deformities, shortened long bones, and reproductive problems. Here we generated and systematically analyzed the skeletal phenotype of a new global Bril KO/LacZ knockin mouse model. KO mice reproduced and thrived normally up to 12 month of age. The skeletal phenotype of KO and WT littermates was assessed at embryonic (E13.5 to E18.5) and postnatal (2 days, 3 weeks, 3 months and 8 months) time-points. Embryos from E13.5 through to E18.5 showed significant X-Gal staining in all skeletal elements without any apparent patterning anomalies. Although bone deformities were never observed at any postnatal ages, minor and transient differences were noted in terms of bone length and static uCT parameters, but not systematically across all ages and genders. These changes, however, were not accompanied by significant alteration in bone material properties as assessed by a 3-point bending test. In addition, no changes were detected in circulating serum markers of bone turnover (P1NP, CTX-I, and osteocalcin). Gene expression monitoring also revealed no major impact of the loss of BRIL. Further, when mice were challenged with a surgically-induced fracture in tibia, bones repaired equally well in the KO mice as compared to WT. Finally, we showed that BRIL C-terminus is not a bona fide binding site for calcium. In conclusion, our in depth analysis suggest that skeletal patterning, bone mass accrual and remodeling in mice proceeded independent of BRIL.",2017 Sep 7,"['Patoine, Alexa', 'Husseini, Abdallah', 'Kasaai, Bahar', 'Gaumond, Marie-Hélène', 'Moffatt, Pierre']",PLoS One,,,True
5a2d0804fc8a4c5d6c661deca4e3150e5cbc77d5,PMC,The lifecycle of the Ebola virus in host cells,http://dx.doi.org/10.18632/oncotarget.18498,PMC5589696,28903457,CC BY,"Ebola haemorrhagic fever causes deadly disease in humans and non-human primates resulting from infection with the Ebola virus (EBOV) genus of the family Filoviridae. However, the mechanisms of EBOV lifecycle in host cells, including viral entry, membrane fusion, RNP formation, GP-tetherin interaction, and VP40-inner leaflet association remain poorly understood. This review describes the biological functions of EBOV proteins and their roles in the lifecycle, summarizes the factors related to EBOV proteins or RNA expression throughout the different phases, and reviews advances with regards to the molecular events and mechanisms of the EBOV lifecycle. Furthermore, the review outlines the aspects remain unclear that urgently need to be solved in future research.",2017 Jun 15,"['Yu, Dong-Shan', 'Weng, Tian-Hao', 'Wu, Xiao-Xin', 'Wang, Frederick X.C.', 'Lu, Xiang-Yun', 'Wu, Hai-Bo', 'Wu, Nan-Ping', 'Li, Lan-Juan', 'Yao, Hang-Ping']",Oncotarget,,,True
ed53facd3e1c8ca47607dc596093f1346ff65ce9,PMC,Virulence of current German PEDV strains in suckling pigs and investigation of protective effects of maternally derived antibodies,http://dx.doi.org/10.1038/s41598-017-11160-w,PMC5589859,28883628,CC BY,"Porcine epidemic diarrhea (PED) has caused tremendous losses to the United States pig industry since 2013. From 2014, outbreaks were also reported from Central Europe. To characterize the Central European PEDV strains regarding their virulence in suckling piglets, and to assess the protective effect of maternally derived antibodies (MDA), four trial groups were randomly assigned, each consisting of two pregnant sows and their litter. To induce MDA in a subset of piglets, two sows received a cell culture-adapted PEDV strain, and another two sows were inoculated with field material from German PED outbreaks. Four sows stayed naïve. Subsequently, all piglets were inoculated with the corresponding PEDV strains at an age of 3 to 6 days, and virus shedding, clinical signs and occurrence of specific antibodies were assessed. Piglets without MDA showed a morbidity of 100% and low lethality, while almost all MDA-positive piglets stayed clinically healthy and showed considerably lower virus shedding. Taken together, the Central European PEDV strains showed rather low virulence under experimental conditions, and pre-inoculation of sows led to a solid protection of their offspring. The latter is the prerequisite for a sow vaccination concept that could help to prevent PED induced losses in the piglet sector.",2017 Sep 7,"['Leidenberger, S.', 'Schröder, Ch.', 'Zani, L.', 'Auste, A.', 'Pinette, M.', 'Ambagala, A.', 'Nikolin, V.', 'de Smit, H.', 'Beer, M.', 'Blome, S.']",Sci Rep,,,False
cf4a58774b63c053feab8838400b5bb5f595d401,PMC,Virulence of current German PEDV strains in suckling pigs and investigation of protective effects of maternally derived antibodies,http://dx.doi.org/10.1038/s41598-017-11160-w,PMC5589859,28883628,CC BY,"Porcine epidemic diarrhea (PED) has caused tremendous losses to the United States pig industry since 2013. From 2014, outbreaks were also reported from Central Europe. To characterize the Central European PEDV strains regarding their virulence in suckling piglets, and to assess the protective effect of maternally derived antibodies (MDA), four trial groups were randomly assigned, each consisting of two pregnant sows and their litter. To induce MDA in a subset of piglets, two sows received a cell culture-adapted PEDV strain, and another two sows were inoculated with field material from German PED outbreaks. Four sows stayed naïve. Subsequently, all piglets were inoculated with the corresponding PEDV strains at an age of 3 to 6 days, and virus shedding, clinical signs and occurrence of specific antibodies were assessed. Piglets without MDA showed a morbidity of 100% and low lethality, while almost all MDA-positive piglets stayed clinically healthy and showed considerably lower virus shedding. Taken together, the Central European PEDV strains showed rather low virulence under experimental conditions, and pre-inoculation of sows led to a solid protection of their offspring. The latter is the prerequisite for a sow vaccination concept that could help to prevent PED induced losses in the piglet sector.",2017 Sep 7,"['Leidenberger, S.', 'Schröder, Ch.', 'Zani, L.', 'Auste, A.', 'Pinette, M.', 'Ambagala, A.', 'Nikolin, V.', 'de Smit, H.', 'Beer, M.', 'Blome, S.']",Sci Rep,,,True
cbcbf427bdac380dfdd327ab0fb83567f20b1987,PMC,Virome analysis for identification of novel mammalian viruses in bats from Southeast China,http://dx.doi.org/10.1038/s41598-017-11384-w,PMC5589946,28883450,CC BY,"Bats have been shown as important mammal resevoirs to carry a variety of zoonotic pathogens. To analyze pathogenic species in bats from southeast coastal regions of China, we performed metagenomic sequencing technology for high throughput sequencing of six sentinels from southeast coastal area of China. We obtained 5,990,261 high quality reads from intestine and lung tissue of 235 bats, including 2,975,371 assembled sequences. 631,490 reads predicted overlapping sequences for the open reading frame (ORF), which accounts for 2.37% of all the sequences (15,012/631,490). Further, the acquired virus sequences were classified into 25 viral families, including 16 vertebrate viruses, four plant viruses and five insect viruses. All bat samples were screened by specific PCR and phylogenetic analysis. Using these techniques, we discovered many novel bat viruses and some bat viruses closely-related to known human/animal pathogens, including coronavirus, norovirus, adenovirus, bocavirus, astrovirus, and circovirus. In summary, this study extended our understanding of bats as the viral reservoirs. Additionally, it also provides a basis for furher studying the transmission of viruses from bats to humans.",2017 Sep 7,"['Hu, Dan', 'Zhu, Changqiang', 'Wang, Yi', 'Ai, Lele', 'Yang, Lu', 'Ye, Fuqiang', 'Ding, Chenxi', 'Chen, Jiafeng', 'He, Biao', 'Zhu, Jin', 'Qian, Hui', 'Xu, Wenrong', 'Feng, Youjun', 'Tan, Weilong', 'Wang, Changjun']",Sci Rep,,,True
c8d60caf44017989b3b9633350fc1d2efda570a5,PMC,"Population genetics, community of parasites, and resistance to rodenticides in an urban brown rat (Rattus norvegicus) population",http://dx.doi.org/10.1371/journal.pone.0184015,PMC5590879,28886097,CC BY,"Brown rats are one of the most widespread urban species worldwide. Despite the nuisances they induce and their potential role as a zoonotic reservoir, knowledge on urban rat populations remains scarce. The main purpose of this study was to characterize an urban brown rat population from Chanteraines park (Hauts-de-Seine, France), with regards to haematology, population genetics, immunogenic diversity, resistance to anticoagulant rodenticides, and community of parasites. Haematological parameters were measured. Population genetics was investigated using 13 unlinked microsatellite loci. Immunogenic diversity was assessed for Mhc-Drb. Frequency of the Y139F mutation (conferring resistance to rodenticides) and two linked microsatellites were studied, concurrently with the presence of anticoagulant residues in the liver. Combination of microscopy and molecular methods were used to investigate the occurrence of 25 parasites. Statistical approaches were used to explore multiple parasite relationships and model parasite occurrence. Eighty-six rats were caught. The first haematological data for a wild urban R. norvegicus population was reported. Genetic results suggested high genetic diversity and connectivity between Chanteraines rats and surrounding population(s). We found a high prevalence (55.8%) of the mutation Y139F and presence of rodenticide residues in 47.7% of the sampled individuals. The parasite species richness was high (16). Seven potential zoonotic pathogens were identified, together with a surprisingly high diversity of Leptospira species (4). Chanteraines rat population is not closed, allowing gene flow and making eradication programs challenging, particularly because rodenticide resistance is highly prevalent. Parasitological results showed that co-infection is more a rule than an exception. Furthermore, the presence of several potential zoonotic pathogens, of which four Leptospira species, in this urban rat population raised its role in the maintenance and spread of these pathogens. Our findings should stimulate future discussions about the development of a long-term rat-control management program in Chanteraines urban park.",2017 Sep 8,"['Desvars-Larrive, Amélie', 'Pascal, Michel', 'Gasqui, Patrick', 'Cosson, Jean-François', 'Benoît, Etienne', 'Lattard, Virginie', 'Crespin, Laurent', 'Lorvelec, Olivier', 'Pisanu, Benoît', 'Teynié, Alexandre', 'Vayssier-Taussat, Muriel', 'Bonnet, Sarah', 'Marianneau, Philippe', 'Lacôte, Sandra', 'Bourhy, Pascale', 'Berny, Philippe', 'Pavio, Nicole', 'Le Poder, Sophie', 'Gilot-Fromont, Emmanuelle', 'Jourdain, Elsa', 'Hammed, Abdessalem', 'Fourel, Isabelle', 'Chikh, Farid', 'Vourc’h, Gwenaël']",PLoS One,,,True
f1a9bb377e28527cda63947734bbd74fe64207a5,PMC,"Population genetics, community of parasites, and resistance to rodenticides in an urban brown rat (Rattus norvegicus) population",http://dx.doi.org/10.1371/journal.pone.0184015,PMC5590879,28886097,CC BY,"Brown rats are one of the most widespread urban species worldwide. Despite the nuisances they induce and their potential role as a zoonotic reservoir, knowledge on urban rat populations remains scarce. The main purpose of this study was to characterize an urban brown rat population from Chanteraines park (Hauts-de-Seine, France), with regards to haematology, population genetics, immunogenic diversity, resistance to anticoagulant rodenticides, and community of parasites. Haematological parameters were measured. Population genetics was investigated using 13 unlinked microsatellite loci. Immunogenic diversity was assessed for Mhc-Drb. Frequency of the Y139F mutation (conferring resistance to rodenticides) and two linked microsatellites were studied, concurrently with the presence of anticoagulant residues in the liver. Combination of microscopy and molecular methods were used to investigate the occurrence of 25 parasites. Statistical approaches were used to explore multiple parasite relationships and model parasite occurrence. Eighty-six rats were caught. The first haematological data for a wild urban R. norvegicus population was reported. Genetic results suggested high genetic diversity and connectivity between Chanteraines rats and surrounding population(s). We found a high prevalence (55.8%) of the mutation Y139F and presence of rodenticide residues in 47.7% of the sampled individuals. The parasite species richness was high (16). Seven potential zoonotic pathogens were identified, together with a surprisingly high diversity of Leptospira species (4). Chanteraines rat population is not closed, allowing gene flow and making eradication programs challenging, particularly because rodenticide resistance is highly prevalent. Parasitological results showed that co-infection is more a rule than an exception. Furthermore, the presence of several potential zoonotic pathogens, of which four Leptospira species, in this urban rat population raised its role in the maintenance and spread of these pathogens. Our findings should stimulate future discussions about the development of a long-term rat-control management program in Chanteraines urban park.",2017 Sep 8,"['Desvars-Larrive, Amélie', 'Pascal, Michel', 'Gasqui, Patrick', 'Cosson, Jean-François', 'Benoît, Etienne', 'Lattard, Virginie', 'Crespin, Laurent', 'Lorvelec, Olivier', 'Pisanu, Benoît', 'Teynié, Alexandre', 'Vayssier-Taussat, Muriel', 'Bonnet, Sarah', 'Marianneau, Philippe', 'Lacôte, Sandra', 'Bourhy, Pascale', 'Berny, Philippe', 'Pavio, Nicole', 'Le Poder, Sophie', 'Gilot-Fromont, Emmanuelle', 'Jourdain, Elsa', 'Hammed, Abdessalem', 'Fourel, Isabelle', 'Chikh, Farid', 'Vourc’h, Gwenaël']",PLoS One,,,True
1a6c94a998e8721893e50bfc84e48465e54e1bcc,PMC,"Population genetics, community of parasites, and resistance to rodenticides in an urban brown rat (Rattus norvegicus) population",http://dx.doi.org/10.1371/journal.pone.0184015,PMC5590879,28886097,CC BY,"Brown rats are one of the most widespread urban species worldwide. Despite the nuisances they induce and their potential role as a zoonotic reservoir, knowledge on urban rat populations remains scarce. The main purpose of this study was to characterize an urban brown rat population from Chanteraines park (Hauts-de-Seine, France), with regards to haematology, population genetics, immunogenic diversity, resistance to anticoagulant rodenticides, and community of parasites. Haematological parameters were measured. Population genetics was investigated using 13 unlinked microsatellite loci. Immunogenic diversity was assessed for Mhc-Drb. Frequency of the Y139F mutation (conferring resistance to rodenticides) and two linked microsatellites were studied, concurrently with the presence of anticoagulant residues in the liver. Combination of microscopy and molecular methods were used to investigate the occurrence of 25 parasites. Statistical approaches were used to explore multiple parasite relationships and model parasite occurrence. Eighty-six rats were caught. The first haematological data for a wild urban R. norvegicus population was reported. Genetic results suggested high genetic diversity and connectivity between Chanteraines rats and surrounding population(s). We found a high prevalence (55.8%) of the mutation Y139F and presence of rodenticide residues in 47.7% of the sampled individuals. The parasite species richness was high (16). Seven potential zoonotic pathogens were identified, together with a surprisingly high diversity of Leptospira species (4). Chanteraines rat population is not closed, allowing gene flow and making eradication programs challenging, particularly because rodenticide resistance is highly prevalent. Parasitological results showed that co-infection is more a rule than an exception. Furthermore, the presence of several potential zoonotic pathogens, of which four Leptospira species, in this urban rat population raised its role in the maintenance and spread of these pathogens. Our findings should stimulate future discussions about the development of a long-term rat-control management program in Chanteraines urban park.",2017 Sep 8,"['Desvars-Larrive, Amélie', 'Pascal, Michel', 'Gasqui, Patrick', 'Cosson, Jean-François', 'Benoît, Etienne', 'Lattard, Virginie', 'Crespin, Laurent', 'Lorvelec, Olivier', 'Pisanu, Benoît', 'Teynié, Alexandre', 'Vayssier-Taussat, Muriel', 'Bonnet, Sarah', 'Marianneau, Philippe', 'Lacôte, Sandra', 'Bourhy, Pascale', 'Berny, Philippe', 'Pavio, Nicole', 'Le Poder, Sophie', 'Gilot-Fromont, Emmanuelle', 'Jourdain, Elsa', 'Hammed, Abdessalem', 'Fourel, Isabelle', 'Chikh, Farid', 'Vourc’h, Gwenaël']",PLoS One,,,False
f299018d5c77887046306ece2ec9a0c3300aa115,PMC,"Population genetics, community of parasites, and resistance to rodenticides in an urban brown rat (Rattus norvegicus) population",http://dx.doi.org/10.1371/journal.pone.0184015,PMC5590879,28886097,CC BY,"Brown rats are one of the most widespread urban species worldwide. Despite the nuisances they induce and their potential role as a zoonotic reservoir, knowledge on urban rat populations remains scarce. The main purpose of this study was to characterize an urban brown rat population from Chanteraines park (Hauts-de-Seine, France), with regards to haematology, population genetics, immunogenic diversity, resistance to anticoagulant rodenticides, and community of parasites. Haematological parameters were measured. Population genetics was investigated using 13 unlinked microsatellite loci. Immunogenic diversity was assessed for Mhc-Drb. Frequency of the Y139F mutation (conferring resistance to rodenticides) and two linked microsatellites were studied, concurrently with the presence of anticoagulant residues in the liver. Combination of microscopy and molecular methods were used to investigate the occurrence of 25 parasites. Statistical approaches were used to explore multiple parasite relationships and model parasite occurrence. Eighty-six rats were caught. The first haematological data for a wild urban R. norvegicus population was reported. Genetic results suggested high genetic diversity and connectivity between Chanteraines rats and surrounding population(s). We found a high prevalence (55.8%) of the mutation Y139F and presence of rodenticide residues in 47.7% of the sampled individuals. The parasite species richness was high (16). Seven potential zoonotic pathogens were identified, together with a surprisingly high diversity of Leptospira species (4). Chanteraines rat population is not closed, allowing gene flow and making eradication programs challenging, particularly because rodenticide resistance is highly prevalent. Parasitological results showed that co-infection is more a rule than an exception. Furthermore, the presence of several potential zoonotic pathogens, of which four Leptospira species, in this urban rat population raised its role in the maintenance and spread of these pathogens. Our findings should stimulate future discussions about the development of a long-term rat-control management program in Chanteraines urban park.",2017 Sep 8,"['Desvars-Larrive, Amélie', 'Pascal, Michel', 'Gasqui, Patrick', 'Cosson, Jean-François', 'Benoît, Etienne', 'Lattard, Virginie', 'Crespin, Laurent', 'Lorvelec, Olivier', 'Pisanu, Benoît', 'Teynié, Alexandre', 'Vayssier-Taussat, Muriel', 'Bonnet, Sarah', 'Marianneau, Philippe', 'Lacôte, Sandra', 'Bourhy, Pascale', 'Berny, Philippe', 'Pavio, Nicole', 'Le Poder, Sophie', 'Gilot-Fromont, Emmanuelle', 'Jourdain, Elsa', 'Hammed, Abdessalem', 'Fourel, Isabelle', 'Chikh, Farid', 'Vourc’h, Gwenaël']",PLoS One,,,False
0b2efe652b70f53458b1fa5c765f9878dbbd3610,PMC,"Population genetics, community of parasites, and resistance to rodenticides in an urban brown rat (Rattus norvegicus) population",http://dx.doi.org/10.1371/journal.pone.0184015,PMC5590879,28886097,CC BY,"Brown rats are one of the most widespread urban species worldwide. Despite the nuisances they induce and their potential role as a zoonotic reservoir, knowledge on urban rat populations remains scarce. The main purpose of this study was to characterize an urban brown rat population from Chanteraines park (Hauts-de-Seine, France), with regards to haematology, population genetics, immunogenic diversity, resistance to anticoagulant rodenticides, and community of parasites. Haematological parameters were measured. Population genetics was investigated using 13 unlinked microsatellite loci. Immunogenic diversity was assessed for Mhc-Drb. Frequency of the Y139F mutation (conferring resistance to rodenticides) and two linked microsatellites were studied, concurrently with the presence of anticoagulant residues in the liver. Combination of microscopy and molecular methods were used to investigate the occurrence of 25 parasites. Statistical approaches were used to explore multiple parasite relationships and model parasite occurrence. Eighty-six rats were caught. The first haematological data for a wild urban R. norvegicus population was reported. Genetic results suggested high genetic diversity and connectivity between Chanteraines rats and surrounding population(s). We found a high prevalence (55.8%) of the mutation Y139F and presence of rodenticide residues in 47.7% of the sampled individuals. The parasite species richness was high (16). Seven potential zoonotic pathogens were identified, together with a surprisingly high diversity of Leptospira species (4). Chanteraines rat population is not closed, allowing gene flow and making eradication programs challenging, particularly because rodenticide resistance is highly prevalent. Parasitological results showed that co-infection is more a rule than an exception. Furthermore, the presence of several potential zoonotic pathogens, of which four Leptospira species, in this urban rat population raised its role in the maintenance and spread of these pathogens. Our findings should stimulate future discussions about the development of a long-term rat-control management program in Chanteraines urban park.",2017 Sep 8,"['Desvars-Larrive, Amélie', 'Pascal, Michel', 'Gasqui, Patrick', 'Cosson, Jean-François', 'Benoît, Etienne', 'Lattard, Virginie', 'Crespin, Laurent', 'Lorvelec, Olivier', 'Pisanu, Benoît', 'Teynié, Alexandre', 'Vayssier-Taussat, Muriel', 'Bonnet, Sarah', 'Marianneau, Philippe', 'Lacôte, Sandra', 'Bourhy, Pascale', 'Berny, Philippe', 'Pavio, Nicole', 'Le Poder, Sophie', 'Gilot-Fromont, Emmanuelle', 'Jourdain, Elsa', 'Hammed, Abdessalem', 'Fourel, Isabelle', 'Chikh, Farid', 'Vourc’h, Gwenaël']",PLoS One,,,False
5665e92208f724ab816c582e61eea5e2cf5a92fa,PMC,"Population genetics, community of parasites, and resistance to rodenticides in an urban brown rat (Rattus norvegicus) population",http://dx.doi.org/10.1371/journal.pone.0184015,PMC5590879,28886097,CC BY,"Brown rats are one of the most widespread urban species worldwide. Despite the nuisances they induce and their potential role as a zoonotic reservoir, knowledge on urban rat populations remains scarce. The main purpose of this study was to characterize an urban brown rat population from Chanteraines park (Hauts-de-Seine, France), with regards to haematology, population genetics, immunogenic diversity, resistance to anticoagulant rodenticides, and community of parasites. Haematological parameters were measured. Population genetics was investigated using 13 unlinked microsatellite loci. Immunogenic diversity was assessed for Mhc-Drb. Frequency of the Y139F mutation (conferring resistance to rodenticides) and two linked microsatellites were studied, concurrently with the presence of anticoagulant residues in the liver. Combination of microscopy and molecular methods were used to investigate the occurrence of 25 parasites. Statistical approaches were used to explore multiple parasite relationships and model parasite occurrence. Eighty-six rats were caught. The first haematological data for a wild urban R. norvegicus population was reported. Genetic results suggested high genetic diversity and connectivity between Chanteraines rats and surrounding population(s). We found a high prevalence (55.8%) of the mutation Y139F and presence of rodenticide residues in 47.7% of the sampled individuals. The parasite species richness was high (16). Seven potential zoonotic pathogens were identified, together with a surprisingly high diversity of Leptospira species (4). Chanteraines rat population is not closed, allowing gene flow and making eradication programs challenging, particularly because rodenticide resistance is highly prevalent. Parasitological results showed that co-infection is more a rule than an exception. Furthermore, the presence of several potential zoonotic pathogens, of which four Leptospira species, in this urban rat population raised its role in the maintenance and spread of these pathogens. Our findings should stimulate future discussions about the development of a long-term rat-control management program in Chanteraines urban park.",2017 Sep 8,"['Desvars-Larrive, Amélie', 'Pascal, Michel', 'Gasqui, Patrick', 'Cosson, Jean-François', 'Benoît, Etienne', 'Lattard, Virginie', 'Crespin, Laurent', 'Lorvelec, Olivier', 'Pisanu, Benoît', 'Teynié, Alexandre', 'Vayssier-Taussat, Muriel', 'Bonnet, Sarah', 'Marianneau, Philippe', 'Lacôte, Sandra', 'Bourhy, Pascale', 'Berny, Philippe', 'Pavio, Nicole', 'Le Poder, Sophie', 'Gilot-Fromont, Emmanuelle', 'Jourdain, Elsa', 'Hammed, Abdessalem', 'Fourel, Isabelle', 'Chikh, Farid', 'Vourc’h, Gwenaël']",PLoS One,,,False
a2813c4975ae511e8e156daa2c5d81cb93bdcc05,PMC,Hong Kong Hospital Authority resource efficiency evaluation: Via a novel DEA-Malmquist model and Tobit regression model,http://dx.doi.org/10.1371/journal.pone.0184211,PMC5590922,28886087,CC BY,"The Hospital Authority (HA) is a statutory body managing all the public hospitals and institutes in Hong Kong (HK). In recent decades, Hong Kong Hospital Authority (HKHA) has been making efforts to improve the healthcare services, but there still exist some problems like unfair resource allocation and poor management, as reported by the Hong Kong medical legislative committee. One critical consequence of these problems is low healthcare efficiency of hospitals, leading to low satisfaction among patients. Moreover, HKHA also suffers from the conflict between limited resource and growing demand. An effective evaluation of HA is important for resource planning and healthcare decision making. In this paper, we propose a two-phase method to evaluate HA efficiency for reducing healthcare expenditure and improving healthcare service. Specifically, in Phase I, we measure the HKHA efficiency changes from 2000 to 2013 by applying a novel DEA-Malmquist index with undesirable factors. In Phase II, we further explore the impact of some exogenous factors (e.g., population density) on HKHA efficiency by Tobit regression model. Empirical results show that there are significant differences between the efficiencies of different hospitals and clusters. In particular, it is found that the public hospital serving in a richer district has a relatively lower efficiency. To a certain extent, this reflects the socioeconomic reality in HK that people with better economic condition prefers receiving higher quality service from the private hospitals.",2017 Sep 8,"['Guo, Hainan', 'Zhao, Yang', 'Niu, Tie', 'Tsui, Kwok-Leung']",PLoS One,,,True
250615c975f713cb3e2b09e7e9718fa2eb095a79,PMC,Toxoplasma gondii seroprevalence varies by cat breed,http://dx.doi.org/10.1371/journal.pone.0184659,PMC5590984,28886182,CC BY,"Toxoplasma gondii is a widespread zoonotic parasite that is relevant for veterinary and public health. The domestic cat, the definitive host species with the largest worldwide population, has become evolutionarily and epidemiologically the most important host of T. gondii. The outcome of T. gondii infection is influenced by congenital and acquired host characteristics. We detected differences in T. gondii seroprevalence by cat breed in our previous studies. The aims of this study were to estimate T. gondii seroprevalence in selected domestic cat breeds, and to evaluate whether being of a certain breed is associated with T. gondii seropositivity, when the age and lifestyle of the cat are taken into account. The studied breeds were the Birman, British Shorthair, Burmese, Korat, Norwegian Forest Cat, Ocicat, Persian, and Siamese. Plasma samples were analyzed for the presence of immunoglobulin G antibodies against T. gondii with a commercial direct agglutination test at dilution 1:40. The samples were accompanied by owner-completed questionnaires that provided background data on the cats. Overall, 41.12% of the 1121 cats tested seropositive, and the seroprevalence increased with age. The Burmese had the lowest seroprevalence (18.82%) and the Persian had the highest (60.00%). According to the final multivariable logistic regression model, the odds to test seropositive were four to seven times higher in Birmans, Ocicats, Norwegian Forest Cats, and Persians when compared with the Burmese, while older age and receiving raw meat were also risk factors for T. gondii seropositivity. This study showed that T. gondii seroprevalence varies by cat breed and identified being of certain breeds, older age, and receiving raw meat as risk factors for seropositivity.",2017 Sep 8,"['Must, Kärt', 'Hytönen, Marjo K.', 'Orro, Toomas', 'Lohi, Hannes', 'Jokelainen, Pikka']",PLoS One,,,True
068a5080b09ba846d95bc76084f1a9ef6de7dcd7,PMC,Toxoplasma gondii seroprevalence varies by cat breed,http://dx.doi.org/10.1371/journal.pone.0184659,PMC5590984,28886182,CC BY,"Toxoplasma gondii is a widespread zoonotic parasite that is relevant for veterinary and public health. The domestic cat, the definitive host species with the largest worldwide population, has become evolutionarily and epidemiologically the most important host of T. gondii. The outcome of T. gondii infection is influenced by congenital and acquired host characteristics. We detected differences in T. gondii seroprevalence by cat breed in our previous studies. The aims of this study were to estimate T. gondii seroprevalence in selected domestic cat breeds, and to evaluate whether being of a certain breed is associated with T. gondii seropositivity, when the age and lifestyle of the cat are taken into account. The studied breeds were the Birman, British Shorthair, Burmese, Korat, Norwegian Forest Cat, Ocicat, Persian, and Siamese. Plasma samples were analyzed for the presence of immunoglobulin G antibodies against T. gondii with a commercial direct agglutination test at dilution 1:40. The samples were accompanied by owner-completed questionnaires that provided background data on the cats. Overall, 41.12% of the 1121 cats tested seropositive, and the seroprevalence increased with age. The Burmese had the lowest seroprevalence (18.82%) and the Persian had the highest (60.00%). According to the final multivariable logistic regression model, the odds to test seropositive were four to seven times higher in Birmans, Ocicats, Norwegian Forest Cats, and Persians when compared with the Burmese, while older age and receiving raw meat were also risk factors for T. gondii seropositivity. This study showed that T. gondii seroprevalence varies by cat breed and identified being of certain breeds, older age, and receiving raw meat as risk factors for seropositivity.",2017 Sep 8,"['Must, Kärt', 'Hytönen, Marjo K.', 'Orro, Toomas', 'Lohi, Hannes', 'Jokelainen, Pikka']",PLoS One,,,False
e505d4ad17c8007a18529518f34fc491594e70e4,PMC,Toxoplasma gondii seroprevalence varies by cat breed,http://dx.doi.org/10.1371/journal.pone.0184659,PMC5590984,28886182,CC BY,"Toxoplasma gondii is a widespread zoonotic parasite that is relevant for veterinary and public health. The domestic cat, the definitive host species with the largest worldwide population, has become evolutionarily and epidemiologically the most important host of T. gondii. The outcome of T. gondii infection is influenced by congenital and acquired host characteristics. We detected differences in T. gondii seroprevalence by cat breed in our previous studies. The aims of this study were to estimate T. gondii seroprevalence in selected domestic cat breeds, and to evaluate whether being of a certain breed is associated with T. gondii seropositivity, when the age and lifestyle of the cat are taken into account. The studied breeds were the Birman, British Shorthair, Burmese, Korat, Norwegian Forest Cat, Ocicat, Persian, and Siamese. Plasma samples were analyzed for the presence of immunoglobulin G antibodies against T. gondii with a commercial direct agglutination test at dilution 1:40. The samples were accompanied by owner-completed questionnaires that provided background data on the cats. Overall, 41.12% of the 1121 cats tested seropositive, and the seroprevalence increased with age. The Burmese had the lowest seroprevalence (18.82%) and the Persian had the highest (60.00%). According to the final multivariable logistic regression model, the odds to test seropositive were four to seven times higher in Birmans, Ocicats, Norwegian Forest Cats, and Persians when compared with the Burmese, while older age and receiving raw meat were also risk factors for T. gondii seropositivity. This study showed that T. gondii seroprevalence varies by cat breed and identified being of certain breeds, older age, and receiving raw meat as risk factors for seropositivity.",2017 Sep 8,"['Must, Kärt', 'Hytönen, Marjo K.', 'Orro, Toomas', 'Lohi, Hannes', 'Jokelainen, Pikka']",PLoS One,,,False
f9b5c2dca99233ea83f15402efa633b7657782b6,PMC,Toxoplasma gondii seroprevalence varies by cat breed,http://dx.doi.org/10.1371/journal.pone.0184659,PMC5590984,28886182,CC BY,"Toxoplasma gondii is a widespread zoonotic parasite that is relevant for veterinary and public health. The domestic cat, the definitive host species with the largest worldwide population, has become evolutionarily and epidemiologically the most important host of T. gondii. The outcome of T. gondii infection is influenced by congenital and acquired host characteristics. We detected differences in T. gondii seroprevalence by cat breed in our previous studies. The aims of this study were to estimate T. gondii seroprevalence in selected domestic cat breeds, and to evaluate whether being of a certain breed is associated with T. gondii seropositivity, when the age and lifestyle of the cat are taken into account. The studied breeds were the Birman, British Shorthair, Burmese, Korat, Norwegian Forest Cat, Ocicat, Persian, and Siamese. Plasma samples were analyzed for the presence of immunoglobulin G antibodies against T. gondii with a commercial direct agglutination test at dilution 1:40. The samples were accompanied by owner-completed questionnaires that provided background data on the cats. Overall, 41.12% of the 1121 cats tested seropositive, and the seroprevalence increased with age. The Burmese had the lowest seroprevalence (18.82%) and the Persian had the highest (60.00%). According to the final multivariable logistic regression model, the odds to test seropositive were four to seven times higher in Birmans, Ocicats, Norwegian Forest Cats, and Persians when compared with the Burmese, while older age and receiving raw meat were also risk factors for T. gondii seropositivity. This study showed that T. gondii seroprevalence varies by cat breed and identified being of certain breeds, older age, and receiving raw meat as risk factors for seropositivity.",2017 Sep 8,"['Must, Kärt', 'Hytönen, Marjo K.', 'Orro, Toomas', 'Lohi, Hannes', 'Jokelainen, Pikka']",PLoS One,,,False
3264f113b3ecd2f724553fa847bc5f3f8800dd69,PMC,Toxoplasma gondii seroprevalence varies by cat breed,http://dx.doi.org/10.1371/journal.pone.0184659,PMC5590984,28886182,CC BY,"Toxoplasma gondii is a widespread zoonotic parasite that is relevant for veterinary and public health. The domestic cat, the definitive host species with the largest worldwide population, has become evolutionarily and epidemiologically the most important host of T. gondii. The outcome of T. gondii infection is influenced by congenital and acquired host characteristics. We detected differences in T. gondii seroprevalence by cat breed in our previous studies. The aims of this study were to estimate T. gondii seroprevalence in selected domestic cat breeds, and to evaluate whether being of a certain breed is associated with T. gondii seropositivity, when the age and lifestyle of the cat are taken into account. The studied breeds were the Birman, British Shorthair, Burmese, Korat, Norwegian Forest Cat, Ocicat, Persian, and Siamese. Plasma samples were analyzed for the presence of immunoglobulin G antibodies against T. gondii with a commercial direct agglutination test at dilution 1:40. The samples were accompanied by owner-completed questionnaires that provided background data on the cats. Overall, 41.12% of the 1121 cats tested seropositive, and the seroprevalence increased with age. The Burmese had the lowest seroprevalence (18.82%) and the Persian had the highest (60.00%). According to the final multivariable logistic regression model, the odds to test seropositive were four to seven times higher in Birmans, Ocicats, Norwegian Forest Cats, and Persians when compared with the Burmese, while older age and receiving raw meat were also risk factors for T. gondii seropositivity. This study showed that T. gondii seroprevalence varies by cat breed and identified being of certain breeds, older age, and receiving raw meat as risk factors for seropositivity.",2017 Sep 8,"['Must, Kärt', 'Hytönen, Marjo K.', 'Orro, Toomas', 'Lohi, Hannes', 'Jokelainen, Pikka']",PLoS One,,,False
9f1c0f42e5cf2ca445e6892632f898cb3197cae3,PMC,Toxoplasma gondii seroprevalence varies by cat breed,http://dx.doi.org/10.1371/journal.pone.0184659,PMC5590984,28886182,CC BY,"Toxoplasma gondii is a widespread zoonotic parasite that is relevant for veterinary and public health. The domestic cat, the definitive host species with the largest worldwide population, has become evolutionarily and epidemiologically the most important host of T. gondii. The outcome of T. gondii infection is influenced by congenital and acquired host characteristics. We detected differences in T. gondii seroprevalence by cat breed in our previous studies. The aims of this study were to estimate T. gondii seroprevalence in selected domestic cat breeds, and to evaluate whether being of a certain breed is associated with T. gondii seropositivity, when the age and lifestyle of the cat are taken into account. The studied breeds were the Birman, British Shorthair, Burmese, Korat, Norwegian Forest Cat, Ocicat, Persian, and Siamese. Plasma samples were analyzed for the presence of immunoglobulin G antibodies against T. gondii with a commercial direct agglutination test at dilution 1:40. The samples were accompanied by owner-completed questionnaires that provided background data on the cats. Overall, 41.12% of the 1121 cats tested seropositive, and the seroprevalence increased with age. The Burmese had the lowest seroprevalence (18.82%) and the Persian had the highest (60.00%). According to the final multivariable logistic regression model, the odds to test seropositive were four to seven times higher in Birmans, Ocicats, Norwegian Forest Cats, and Persians when compared with the Burmese, while older age and receiving raw meat were also risk factors for T. gondii seropositivity. This study showed that T. gondii seroprevalence varies by cat breed and identified being of certain breeds, older age, and receiving raw meat as risk factors for seropositivity.",2017 Sep 8,"['Must, Kärt', 'Hytönen, Marjo K.', 'Orro, Toomas', 'Lohi, Hannes', 'Jokelainen, Pikka']",PLoS One,,,False
e703a33d5803f827c3d57a19385c0c2cbc2830e9,PMC,Prevalence of enteropathogens and their antibiotic sensitivity pattern in puppies with hemorrhagic gastroenteritis,http://dx.doi.org/10.14202/vetworld.2017.859-863,PMC5591469,28919674,CC BY,"AIM: Hemorrhagic gastroenteritis (HGE) ranging from mild to severe forms is commonly encountered in puppies. The aim of the study was to identify the prevalence of common enteropathogens and the antibiotic sensitivity pattern in puppies reported with HGE. MATERIALS AND METHODS: The canine HGE activity index, with little modification, was adopted to identify Grade III/severely affected puppies below 6 months of age. Fecal polymerase chain reaction (PCR) assay was employed to screen and compare the enteropathogens in puppies with hemorrhagic diarrhea and healthy control. RESULTS: Canine parvovirus 2b was identified in 90.3% of the diarrheic and 10% of the non-diarrheic healthy puppies. Clostridium difficile was identified in all the diarrheic puppies and in 80% of the healthy puppies. Among the diarrheic puppies, 17.7% were positive for Clostridium perfringens enterotoxin, 9.7% were positive for C. perfringens alpha toxin, 6.4% were positive for Escherichia coli shiga toxin, 6.4% were positive for E. coli enterotoxin (LT), and 3.2% were positive for canine distemper virus. Whereas, none of the healthy puppies were positive for these bacteria and toxins. Fecal antibiotic sensitivity test pattern revealed gentamicin to be sensitive in 95% of the cases, azithromycin in 50%, enrofloxacin in 25%, cefotaxime in 20%, and tetracycline in 5% of the cases. CONCLUSION: Parvoviral enteritis is predominant among puppies. Yet, bacteria and their toxins also play an important role in HGE. Gentamicin has higher sensitivity against the enteropathogens associated with the condition.",2017 Aug 4,"['Priya, A. Kokila', 'Balagangatharathilagar, M.', 'Chandrasekaran, D.', 'Parthiban, M.', 'Prathaban, S.']",Vet World,,,True
522701df815e3cc124f0a2f55891879cde0ddffa,PMC,On-farm biosecurity practices and causes of preweaning mortality in Canadian commercial mink kits,http://dx.doi.org/10.1186/s13028-017-0326-8,PMC5591539,28886754,CC BY,"BACKGROUND: Mink are an important animal commodity group in Canada and excessive kit mortality represents a significant loss to production. National biosecurity standards have been developed for Canadian mink farms, but it is unclear how well these standards have been implemented as there are no studies correlating management practices of mink producers with causes of death in mink kits. To that end, we surveyed Ontario mink producers on their biosecurity and management practices and conducted almost 5660 post mortem examinations on found-dead, preweaned kits to characterize mink farm biosecurity practices and causes of death in preweaned kits. RESULTS: We found that very few biosecurity and management practices were uniformly used by producers, despite good awareness of appropriate practices. Use of personal protective equipment was implemented by fewer than 50% of respondents, while control of mink shed access, disinfection of feed containers after use, and use of a rodent control program were the only practices implemented by greater than 70% of respondents. Only 18% of producers reported regular use of antimicrobials in feed or water, although 91% stated they used antimicrobials for treatment of bacterial diseases on a regular basis. On post mortem examination, no gross abnormalities were noted in 71% of the kits, 45% were thought to be stillborn or aborted, 27% had some form of abnormal fluid distribution in the body, and 2% had a congenital malformation. A subset of 69 gastrointestinal tract samples was submitted for bacterial culture, of which 45 samples yielded sufficient growth. Most interesting was the identification of Salmonella enterica serovar Heidelberg in 11% of samples. CONCLUSIONS: The results of this study will provide a benchmark for Canadian mink producers and their veterinarians, defining the areas to which greater attention should be given to ensure more rigorous biosecurity practices are in place. Ultimately, these improvements in practices may contribute to increased mink production and animal well-being. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-017-0326-8) contains supplementary material, which is available to authorized users.",2017 Sep 8,"['Compo, Nicole', 'Pearl, David L.', 'Tapscott, Brian', 'Storer, Amanda', 'Hammermueller, Jutta', 'Brash, Marina', 'Turner, Patricia V.']",Acta Vet Scand,,,True
97f0de00cdfd52961c9a8611c306de5778556eb0,PMC,Gene Expression Networks in the Murine Pulmonary Myocardium Provide Insight into the Pathobiology of Atrial Fibrillation,http://dx.doi.org/10.1534/g3.117.044651,PMC5592927,28720711,CC BY,"The pulmonary myocardium is a muscular coat surrounding the pulmonary and caval veins. Although its definitive physiological function is unknown, it may have a pathological role as the source of ectopic beats initiating atrial fibrillation. How the pulmonary myocardium gains pacemaker function is not clearly defined, although recent evidence indicates that changed transcriptional gene expression networks are at fault. The gene expression profile of this distinct cell type in situ was examined to investigate underlying molecular events that might contribute to atrial fibrillation. Via systems genetics, a whole-lung transcriptome data set from the BXD recombinant inbred mouse resource was analyzed, uncovering a pulmonary cardiomyocyte gene network of 24 transcripts, coordinately regulated by chromosome 1 and 2 loci. Promoter enrichment analysis and interrogation of publicly available ChIP-seq data suggested that transcription of this gene network may be regulated by the concerted activity of NKX2-5, serum response factor, myocyte enhancer factor 2, and also, at a post-transcriptional level, by RNA binding protein motif 20. Gene ontology terms indicate that this gene network overlaps with molecular markers of the stressed heart. Therefore, we propose that perturbed regulation of this gene network might lead to altered calcium handling, myocyte growth, and contractile force contributing to the aberrant electrophysiological properties observed in atrial fibrillation. We reveal novel molecular interactions and pathways representing possible therapeutic targets for atrial fibrillation. In addition, we highlight the utility of recombinant inbred mouse resources in detecting and characterizing gene expression networks of relatively small populations of cells that have a pathological significance.",2017 Jul 18,"['Boutilier, Jordan K.', 'Taylor, Rhonda L.', 'Mann, Tracy', 'McNamara, Elyshia', 'Hoffman, Gary J.', 'Kenny, Jacob', 'Dilley, Rodney J.', 'Henry, Peter', 'Morahan, Grant', 'Laing, Nigel G.', 'Nowak, Kristen J.']",G3 (Bethesda),,,True
5d9c87ae912ec13a723b6d75bd0ab59618a39164,PMC,Small molecular floribundiquinone B derived from medicinal plants inhibits acetylcholinesterase activity,http://dx.doi.org/10.18632/oncotarget.19169,PMC5593632,28915661,CC BY,"Being a neurodegenerative disorder, Alzheimer's disease (AD) is the one of the most terrible diseases. And acetylcholinesterase (AChE) is considered as an important target for treating AD. Acetylcholinesterase inhibitors (AChEI) are considered to be one of the effective drugs for the treatment of AD. The aim of this study is to find a novel potential AChEI as a drug for the treatment of AD. In this study, instead of using the synthetic compounds, we used those extracted from plants to investigate the interaction between floribundiquinone B (FB) and AChE by means of both the experimental approach such as fluorescence spectra, ultraviolet-visible (UV-vis) absorption spectrometry, circular dichroism (CD) and the theoretical approaches such as molecular docking. The findings reported here have provided many useful clues and hints for designing more effective and less toxic drugs against Alzheimer's disease.",2017 Jul 11,"['Niu, Bing', 'Zhang, Mengying', 'Du, Pu', 'Jiang, Li', 'Qin, Rui', 'Su, Qiang', 'Chen, Fuxue', 'Du, Dongshu', 'Shu, Yilai', 'Chou, Kuo-Chen']",Oncotarget,,,True
07e7bb252152b7042ebe8d45f5dc207e19ac8845,PMC,Small molecular floribundiquinone B derived from medicinal plants inhibits acetylcholinesterase activity,http://dx.doi.org/10.18632/oncotarget.19169,PMC5593632,28915661,CC BY,"Being a neurodegenerative disorder, Alzheimer's disease (AD) is the one of the most terrible diseases. And acetylcholinesterase (AChE) is considered as an important target for treating AD. Acetylcholinesterase inhibitors (AChEI) are considered to be one of the effective drugs for the treatment of AD. The aim of this study is to find a novel potential AChEI as a drug for the treatment of AD. In this study, instead of using the synthetic compounds, we used those extracted from plants to investigate the interaction between floribundiquinone B (FB) and AChE by means of both the experimental approach such as fluorescence spectra, ultraviolet-visible (UV-vis) absorption spectrometry, circular dichroism (CD) and the theoretical approaches such as molecular docking. The findings reported here have provided many useful clues and hints for designing more effective and less toxic drugs against Alzheimer's disease.",2017 Jul 11,"['Niu, Bing', 'Zhang, Mengying', 'Du, Pu', 'Jiang, Li', 'Qin, Rui', 'Su, Qiang', 'Chen, Fuxue', 'Du, Dongshu', 'Shu, Yilai', 'Chou, Kuo-Chen']",Oncotarget,,,False
92219161c16ed7c1719549677c40a821fbb54853,PMC,The predictors of 3- and 30-day mortality in 660 MERS-CoV patients,http://dx.doi.org/10.1186/s12879-017-2712-2,PMC5594447,28893197,CC BY,"BACKGROUND: The mortality rate of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) patients is a major challenge in all healthcare systems worldwide. Because the MERS-CoV risk-standardized mortality rates are currently unavailable in the literature, the author concentrated on developing a method to estimate the risk-standardized mortality rates using MERS-CoV 3- and 30-day mortality measures. METHODS: MERS-CoV data in Saudi Arabia is publicly reported and made available through the Saudi Ministry of Health (SMOH) website. The author studied 660 MERS-CoV patients who were reported by the SMOH between December 2, 2014 and November 12, 2016. The data gathered contained basic demographic information (age, gender, and nationality), healthcare worker, source of infection, pre-existing illness, symptomatic, severity of illness, and regions in Saudi Arabia. The status and date of mortality were also reported. Cox-proportional hazard (CPH) models were applied to estimate the hazard ratios for the predictors of 3- and 30-day mortality. RESULTS: 3-day, 30-day, and overall mortality were found to be 13.8%, 28.3%, and 29.8%, respectively. According to CPH, multivariate predictors of 3-day mortality were elderly, non-healthcare workers, illness severity, and hospital-acquired infections (adjusted hazard ratio (aHR) =1.7; 8.8; 6.5; and 2.8, respectively). Multivariate predictors of 30-day mortality were elderly, non-healthcare workers, pre-existing illness, severity of illness, and hospital-acquired infections (aHR =1.7; 19.2; 2.1; 3.7; and 2.9, respectively). CONCLUSIONS: Several factors were identified that could influence mortality outcomes at 3 days and 30 days, including age (elderly), non-healthcare workers, severity of illness, and hospital-acquired infections. The findings can serve as a guide for healthcare practitioners by appropriately identifying and managing potential patients at high risk of death.",2017 Sep 11,"Ahmed, Anwar E.",BMC Infect Dis,,,True
71c95bd39c649d3ba3fee28d11be98cd4019de7f,PMC,Recent expansion and adaptive evolution of the carcinoembryonic antigen family in bats of the Yangochiroptera subgroup,http://dx.doi.org/10.1186/s12864-017-4106-7,PMC5594555,28893191,CC BY,"BACKGROUND: Expansions of gene families are predictive for ongoing genetic adaptation to environmental cues. We describe such an expansion of the carcinoembryonic antigen (CEA) gene family in certain bat families. Members of the CEA family in humans and mice are exploited as cellular receptors by a number of pathogens, possibly due to their function in immunity and reproduction. The CEA family is composed of CEA-related cell adhesion molecules (CEACAMs) and secreted pregnancy-specific glycoproteins (PSGs). PSGs are almost exclusively expressed by trophoblast cells at the maternal-fetal interface. The reason why PSGs exist only in a minority of mammals is still unknown. RESULTS: Analysis of the CEA gene family in bats revealed that in certain bat families, belonging to the subgroup Yangochiroptera but not the Yinpterochiroptera subgroup an expansion of the CEA gene family took place, resulting in approximately one hundred CEA family genes in some species of the Vespertilionidae. The majority of these genes encode secreted PSG-like proteins (further referred to as PSG). Remarkably, we found strong evidence that the ligand-binding domain (IgV-like domain) of PSG is under diversifying positive selection indicating that bat PSGs may interact with structurally highly variable ligands. Such ligands might represent bacterial or viral pathogen adhesins. We have identified two distinct clusters of PSGs in three Myotis species. The two PSG cluster differ in the amino acids under positive selection. One cluster was only expanded in members of the Vespertilionidae while the other was found to be expanded in addition in members of the Miniopteridae and Mormoopidae. Thus one round of PSG expansion may have occurred in an ancestry of all three families and a second only in Vespertilionidae. Although maternal ligands of PSGs may exist selective challenges by two distinct pathogens seem to be likely responsible for the expansion of PSGs in Vespertilionidae. CONCLUSIONS: The rapid expansion of PSGs in certain bat species together with selection for diversification suggest that bat PSGs could be part of a pathogen defense system by serving as decoy receptors and/or regulators of feto-maternal interactions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-017-4106-7) contains supplementary material, which is available to authorized users.",2017 Sep 11,"['Kammerer, Robert', 'Mansfeld, Martin', 'Hänske, Jana', 'Mißbach, Sophie', 'He, Xiaocui', 'Köllner, Bernd', 'Mouchantat, Susan', 'Zimmermann, Wolfgang']",BMC Genomics,,,True
4b2607f3da8bf06c231145105ffd5ca24a07bbda,PMC,Adherence to precautions for preventing the transmission of microorganisms in primary health care: a qualitative study,http://dx.doi.org/10.1186/s12912-017-0245-z,PMC5594588,28919838,CC BY,"BACKGROUND: Health care associated infections (HAIs) are a source of concern worldwide. No health service in any country can be considered HAI risk-free. However, there is scarcity of data on the risks to which both patients and health workers are subject in non-hospital settings. The aim of this study was to identify issues that determine the adherence of professionals to precautions for preventing transmission of microorganisms in primary health care. METHOD: This was a qualitative study, using focus groups of primary health care staff, in two Brazilian municipalities. The data were analysed using content analysis. RESULTS: Four focus groups were conducted with 20 professionals (11 community health workers, 5 nursing assistants and 4 nurses), and the analysed content was organized into four thematic categories. These categories are: low risk perception, weaknesses in knowledge, insufficient in-service training and infrastructure limitations. Participants expressed their weaknesses in knowledge of standard and transmission based precautions, mainly for hand hygiene and tuberculosis. A lack of appropriate resources and standardization in sharps disposal management was also highlighted by the participants. CONCLUSION: The study points out the need to provide in-service training for professionals on the transmission of microorganisms in primary health care to ensure adequate level of risk perception and knowledge. Further recommendations include investment to improve infrastructure to facilitate adherence to precautions and to minimize the risk of disease transmission for both patients and health care workers.",2017 Sep 11,"['Maroldi, Michely Aparecida Cardoso', 'Felix, Adriana Maria da Silva', 'Dias, Ana Angélica Lima', 'Kawagoe, Julia Yaeko', 'Padoveze, Maria Clara', 'Ferreira, Sílvia Alice', 'Zem-Mascarenhas, Sílvia Helena', 'Timmons, Stephen', 'Figueiredo, Rosely Moralez']",BMC Nurs,,,True
66bffe926972c130c5b6239868ae422a8c7d7229,PMC,Associations between media use and health information-seeking behavior on vaccinations in South Korea,http://dx.doi.org/10.1186/s12889-017-4721-x,PMC5594607,28893212,CC BY,"BACKGROUND: Although vaccinations are critical for preventing emerging infectious diseases, scant research has been conducted on risk communication. With socio-economic characteristics, health behavior, and underlying diseases under control, we investigated associations between media use, health information-seeking behavior, health information type, and vaccination in the population. METHODS: This study relied on a national survey of Korean adults (n = 1367). Participants were adult males and females age 20 and older. Web and face-to-face surveys were conducted throughout July 2014. The main outcome was vaccination (categorized as yes or no). Independent variables were time spent on media, frequency of health information-seeking behavior, and types of health information sought. RESULTS: Controlling for co-variates, logistic regression analysis was conducted to identify factors that influence Korean adults being vaccinated. Results revealed that accessible information about emerging infectious diseases, listening to the radio, and reading the newspaper were associated with increased odds of being vaccinated. Active seeking health information as well as being female and of higher socio-economic status were positively correlated with Korean adults being vaccinated. CONCLUSION: It is critical to promote health information-seeking behavior and use diverse media channels to increase acceptance and awareness of emerging infectious diseases and vaccinations. Because there are differences in vaccination awareness depending on social class, it is critical to reduce communication inequality, strengthen accessibility to vaccinations, and devise appropriate risk communication strategies that ensure Korean adults receive vaccinations.",2017 Sep 11,"['Kim, Jiyeon', 'Jung, Minsoo']",BMC Public Health,,,True
68b8a4f644c4195bd6a89ea7e70cd45072ea979e,PMC,Impact of Comorbidity on Fatality Rate of Patients with Middle East Respiratory Syndrome,http://dx.doi.org/10.1038/s41598-017-10402-1,PMC5596001,28900101,CC BY,"To date, 1841 cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported worldwide, with 652 deaths. We used a publically available case line list to explore the effect of relevant factors, notably underlying comorbidities, on fatal outcome of Middle East respiratory syndrome (MERS) cases up to the end of October 2016. A Bayesian Weibull proportional hazards regression model was used to assess the effect of comorbidity, age, epidemic period and sex on the fatality rate of MERS cases and its variation across countries. The crude fatality rate of MERS cases was 32.1% (95% credibility interval (CI): 29.9%, 34.3%). Notably, the incremental change of daily death rate was most prominent during the first week since disease onset with an average increase of 13%, but then stabilized in the remaining two weeks when it only increased 3% on average. Neither sex, nor country of infection were found to have a significant impact on fatality rates after taking into account the age and comorbidity status of patients. After adjusting for age, epidemic period, MERS patients with comorbidity had around 4 times the risk for fatal infection than those without (adjusted hazard ratio of 3.74 (95% CI: 2.57, 5.67)).",2017 Sep 12,"['Yang, Ya-Min', 'Hsu, Chen-Yang', 'Lai, Chao-Chih', 'Yen, Ming-Fang', 'Wikramaratna, Paul S.', 'Chen, Hsiu-Hsi', 'Wang, Tsung-Hsi']",Sci Rep,,,True
61c9abb79e759e71cad30efee033a54f558010db,PMC,Structural insights into the Middle East respiratory syndrome coronavirus 4a protein and its dsRNA binding mechanism,http://dx.doi.org/10.1038/s41598-017-11736-6,PMC5596018,28900197,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) has evolved to navigate through the sophisticated network of a host’s immune system. The immune evasion mechanism including type 1 interferon and protein kinase R-mediated antiviral stress responses has been recently attributed to the involvement of MERS-CoV protein 4a (p4a) that masks the viral dsRNA. However, the structural mechanism of how p4a recognizes and establishes contacts with dsRNA is not well explained. In this study, we report a dynamic mechanism deployed by p4a to engage the viral dsRNA and make it unavailable to the host immune system. Multiple variants of p4a-dsRNA were created and investigated through extensive molecular dynamics procedures to highlight crucial interfacial residues that may be used as potential pharmacophores for future drug development. The structural analysis revealed that p4a exhibits a typical αβββα fold structure, as found in other dsRNA-binding proteins. The α1 helix and the β1-β2 loop play a crucial role in recognizing and establishing contacts with the minor grooves of dsRNA. Further, mutational and binding free energy analyses suggested that in addition to K63 and K67, two other residues, K27 and W45, might also be crucial for p4a-dsRNA stability.",2017 Sep 12,"['Batool, Maria', 'Shah, Masaud', 'Patra, Mahesh Chandra', 'Yesudhas, Dhanusha', 'Choi, Sangdun']",Sci Rep,,,False
4c9f3df22b058cb0b95c53f12cdffd1c5fe1ce93,PMC,Structural insights into the Middle East respiratory syndrome coronavirus 4a protein and its dsRNA binding mechanism,http://dx.doi.org/10.1038/s41598-017-11736-6,PMC5596018,28900197,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) has evolved to navigate through the sophisticated network of a host’s immune system. The immune evasion mechanism including type 1 interferon and protein kinase R-mediated antiviral stress responses has been recently attributed to the involvement of MERS-CoV protein 4a (p4a) that masks the viral dsRNA. However, the structural mechanism of how p4a recognizes and establishes contacts with dsRNA is not well explained. In this study, we report a dynamic mechanism deployed by p4a to engage the viral dsRNA and make it unavailable to the host immune system. Multiple variants of p4a-dsRNA were created and investigated through extensive molecular dynamics procedures to highlight crucial interfacial residues that may be used as potential pharmacophores for future drug development. The structural analysis revealed that p4a exhibits a typical αβββα fold structure, as found in other dsRNA-binding proteins. The α1 helix and the β1-β2 loop play a crucial role in recognizing and establishing contacts with the minor grooves of dsRNA. Further, mutational and binding free energy analyses suggested that in addition to K63 and K67, two other residues, K27 and W45, might also be crucial for p4a-dsRNA stability.",2017 Sep 12,"['Batool, Maria', 'Shah, Masaud', 'Patra, Mahesh Chandra', 'Yesudhas, Dhanusha', 'Choi, Sangdun']",Sci Rep,,,True
727ff12fcef223c2e2c4971ef237c80ee4e58162,PMC,Influenza in long‐term care facilities,http://dx.doi.org/10.1111/irv.12464,PMC5596516,28691237,CC BY,"Long‐term care facility environments and the vulnerability of their residents provide a setting conducive to the rapid spread of influenza virus and other respiratory pathogens. Infections may be introduced by staff, visitors or new or transferred residents, and outbreaks of influenza in such settings can have devastating consequences for individuals, as well as placing extra strain on health services. As the population ages over the coming decades, increased provision of such facilities seems likely. The need for robust infection prevention and control practices will therefore remain of paramount importance if the impact of outbreaks is to be minimised. In this review, we discuss the nature of the problem of influenza in long‐term care facilities, and approaches to preventive and control measures, including vaccination of residents and staff, and the use of antiviral drugs for treatment and prophylaxis, based on currently available evidence.",2017 Sep 26,"['Lansbury, Louise E.', 'Brown, Caroline S.', 'Nguyen‐Van‐Tam, Jonathan S.']",Influenza Other Respir Viruses,,,True
0eae6cad68158cefd58f69d7517a869f9621d3c9,PMC,"Clinical and epidemiologic characteristics of dengue and other etiologic agents among patients with acute febrile illness, Puerto Rico, 2012–2015",http://dx.doi.org/10.1371/journal.pntd.0005859,PMC5597097,28902845,CC0,"Identifying etiologies of acute febrile illnesses (AFI) is challenging due to non-specific presentation and limited availability of diagnostics. Prospective AFI studies provide a methodology to describe the syndrome by age and etiology, findings that can be used to develop case definitions and multiplexed diagnostics to optimize management. We conducted a 3-year prospective AFI study in Puerto Rico. Patients with fever ≤7 days were offered enrollment, and clinical data and specimens were collected at enrollment and upon discharge or follow-up. Blood and oro-nasopharyngeal specimens were tested by RT-PCR and immunodiagnostic methods for infection with dengue viruses (DENV) 1–4, chikungunya virus (CHIKV), influenza A and B viruses (FLU A/B), 12 other respiratory viruses (ORV), enterovirus, Leptospira spp., and Burkholderia pseudomallei. Clinical presentation and laboratory findings of participants infected with DENV were compared to those infected with CHIKV, FLU A/B, and ORV. Clinical predictors of laboratory-positive dengue compared to all other AFI etiologies were determined by age and day post-illness onset (DPO) at presentation. Of 8,996 participants enrolled from May 7, 2012 through May 6, 2015, more than half (54.8%, 4,930) had a pathogen detected. Pathogens most frequently detected were CHIKV (1,635, 18.2%), FLU A/B (1,074, 11.9%), DENV 1–4 (970, 10.8%), and ORV (904, 10.3%). Participants with DENV infection presented later and a higher proportion were hospitalized than those with other diagnoses (46.7% versus 27.3% with ORV, 18.8% with FLU A/B, and 11.2% with CHIKV). Predictors of dengue in participants presenting <3 DPO included leukopenia, thrombocytopenia, headache, eye pain, nausea, and dizziness, while negative predictors were irritability and rhinorrhea. Predictors of dengue in participants presenting 3–5 DPO were leukopenia, thrombocytopenia, facial/neck erythema, nausea, eye pain, signs of poor circulation, and diarrhea; presence of rhinorrhea, cough, and red conjunctiva predicted non-dengue AFI. By enrolling febrile patients at clinical presentation, we identified unbiased predictors of laboratory-positive dengue as compared to other common causes of AFI. These findings can be used to assist in early identification of dengue patients, as well as direct anticipatory guidance and timely initiation of correct clinical management.",2017 Sep 13,"['Tomashek, Kay M.', 'Lorenzi, Olga D.', 'Andújar-Pérez, Doris A.', 'Torres-Velásquez, Brenda C.', 'Hunsperger, Elizabeth A.', 'Munoz-Jordan, Jorge Luis', 'Perez-Padilla, Janice', 'Rivera, Aidsa', 'Gonzalez-Zeno, Gladys E.', 'Sharp, Tyler M.', 'Galloway, Renee L.', 'Glass Elrod, Mindy', 'Mathis, Demetrius L.', 'Oberste, M. Steven', 'Nix, W. Allan', 'Henderson, Elizabeth', 'McQuiston, Jennifer', 'Singleton, Joseph', 'Kato, Cecilia', 'García Gubern, Carlos', 'Santiago-Rivera, William', 'Cruz-Correa, Jesús', 'Muns-Sosa, Robert', 'Ortiz-Rivera, Juan D.', 'Jiménez, Gerson', 'Galarza, Ivonne E.', 'Horiuchi, Kalanthe', 'Margolis, Harold S.', 'Alvarado, Luisa I.']",PLoS Negl Trop Dis,,,True
60d5290b70e9b780174187da93ecf4392b97539d,PMC,"Distinct genetic clades of enterovirus D68 detected in 2010, 2013, and 2015 in Osaka City, Japan",http://dx.doi.org/10.1371/journal.pone.0184335,PMC5597212,28902862,CC BY,"The first upsurge of enterovirus D68 (EV-D68), a causative agent of acute respiratory infections (ARIs), in Japan was reported in Osaka City in 2010. In this study, which began in 2010, we surveyed EV-D68 in children with ARIs and analyzed sequences of EV-D68 strains detected. Real-time PCR of 19 respiratory viruses or subtypes of viruses, including enterovirus, was performed on 2,215 specimens from ARI patients (<10 years of age) collected between November 2010 and December 2015 in Osaka City, Japan. EV-D68 was identified in 18 enterovirus-positive specimens (n = 4 in 2013, n = 1 in 2014, and n = 13 in 2015) by analysis of viral protein 1 (VP1) or VP4 sequences, followed by a BLAST search for similar sequences. All EV-D68 strains were detected between June and October (summer to autumn), except for one strain detected in 2014. A phylogenetic analysis of available VP1 sequences revealed that the Osaka strains detected in 2010, 2013, and 2015 belonged to distinct clusters (Clades C, A, and B [Subclade B3], respectively). Comparison of the 5′ untranslated regions of these viruses showed that Osaka strains in Clades A, B (Subclade B3), and C commonly had deletions at nucleotide positions 681–703 corresponding to the prototype Fermon strain. Clades B and C had deletions from nucleotide positions 713–724. Since the EV-D68 epidemic in 2010, EV-D68 re-emerged in Osaka City, Japan, in 2013 and 2015. Results of this study indicate that distinct clades of EV-D68 contributed to re-emergences of this virus in 2010, 2013, and 2015 in this limited region.",2017 Sep 13,"['Kaida, Atsushi', 'Iritani, Nobuhiro', 'Yamamoto, Seiji P.', 'Kanbayashi, Daiki', 'Hirai, Yuki', 'Togawa, Masao', 'Amo, Kiyoko', 'Kohdera, Urara', 'Nishigaki, Toshinori', 'Shiomi, Masashi', 'Asai, Sadasaburo', 'Kageyama, Tsutomu', 'Kubo, Hideyuki']",PLoS One,,,True
04b5f15cca91a7b810216682780f8ea6e1ab3046,PMC,Identification of diverse viruses in upper respiratory samples in dromedary camels from United Arab Emirates,http://dx.doi.org/10.1371/journal.pone.0184718,PMC5597213,28902913,CC0,"Camels are known carriers for many viral pathogens, including Middle East respiratory syndrome coronavirus (MERS-CoV). It is likely that there are additional, as yet unidentified viruses in camels with the potential to cause disease in humans. In this study, we performed metagenomic sequencing analysis on nasopharyngeal swab samples from 108 MERS-CoV-positive dromedary camels from a live animal market in Abu Dhabi, United Arab Emirates. We obtained a total of 846.72 million high-quality reads from these nasopharyngeal swab samples, of which 2.88 million (0.34%) were related to viral sequences while 512.63 million (60.5%) and 50.87 million (6%) matched bacterial and eukaryotic sequences, respectively. Among the viral reads, sequences related to mammalian viruses from 13 genera in 10 viral families were identified, including Coronaviridae, Nairoviridae, Paramyxoviridae, Parvoviridae, Polyomaviridae, Papillomaviridae, Astroviridae, Picornaviridae, Poxviridae, and Genomoviridae. Some viral sequences belong to known camel or human viruses and others are from potentially novel camel viruses with only limited sequence similarity to virus sequences in GenBank. A total of five potentially novel virus species or strains were identified. Co-infection of at least two recently identified camel coronaviruses was detected in 92.6% of the camels in the study. This study provides a comprehensive survey of viruses in the virome of upper respiratory samples in camels that have extensive contact with the human population.",2017 Sep 13,"['Li, Yan', 'Khalafalla, Abdelmalik Ibrahim', 'Paden, Clinton R.', 'Yusof, Mohammed F.', 'Eltahir, Yassir M.', 'Al Hammadi, Zulaikha M.', 'Tao, Ying', 'Queen, Krista', 'Hosani, Farida Al', 'Gerber, Susan I.', 'Hall, Aron J.', 'Al Muhairi, Salama', 'Tong, Suxiang']",PLoS One,,,True
10883ef2e6ffa38835bcd70dc36d22bf94b9ace0,PMC,Identification of diverse viruses in upper respiratory samples in dromedary camels from United Arab Emirates,http://dx.doi.org/10.1371/journal.pone.0184718,PMC5597213,28902913,CC0,"Camels are known carriers for many viral pathogens, including Middle East respiratory syndrome coronavirus (MERS-CoV). It is likely that there are additional, as yet unidentified viruses in camels with the potential to cause disease in humans. In this study, we performed metagenomic sequencing analysis on nasopharyngeal swab samples from 108 MERS-CoV-positive dromedary camels from a live animal market in Abu Dhabi, United Arab Emirates. We obtained a total of 846.72 million high-quality reads from these nasopharyngeal swab samples, of which 2.88 million (0.34%) were related to viral sequences while 512.63 million (60.5%) and 50.87 million (6%) matched bacterial and eukaryotic sequences, respectively. Among the viral reads, sequences related to mammalian viruses from 13 genera in 10 viral families were identified, including Coronaviridae, Nairoviridae, Paramyxoviridae, Parvoviridae, Polyomaviridae, Papillomaviridae, Astroviridae, Picornaviridae, Poxviridae, and Genomoviridae. Some viral sequences belong to known camel or human viruses and others are from potentially novel camel viruses with only limited sequence similarity to virus sequences in GenBank. A total of five potentially novel virus species or strains were identified. Co-infection of at least two recently identified camel coronaviruses was detected in 92.6% of the camels in the study. This study provides a comprehensive survey of viruses in the virome of upper respiratory samples in camels that have extensive contact with the human population.",2017 Sep 13,"['Li, Yan', 'Khalafalla, Abdelmalik Ibrahim', 'Paden, Clinton R.', 'Yusof, Mohammed F.', 'Eltahir, Yassir M.', 'Al Hammadi, Zulaikha M.', 'Tao, Ying', 'Queen, Krista', 'Hosani, Farida Al', 'Gerber, Susan I.', 'Hall, Aron J.', 'Al Muhairi, Salama', 'Tong, Suxiang']",PLoS One,,,False
c9d760158b06ba138bcf89ec7bb5ea0b13a7dc70,PMC,Identification of diverse viruses in upper respiratory samples in dromedary camels from United Arab Emirates,http://dx.doi.org/10.1371/journal.pone.0184718,PMC5597213,28902913,CC0,"Camels are known carriers for many viral pathogens, including Middle East respiratory syndrome coronavirus (MERS-CoV). It is likely that there are additional, as yet unidentified viruses in camels with the potential to cause disease in humans. In this study, we performed metagenomic sequencing analysis on nasopharyngeal swab samples from 108 MERS-CoV-positive dromedary camels from a live animal market in Abu Dhabi, United Arab Emirates. We obtained a total of 846.72 million high-quality reads from these nasopharyngeal swab samples, of which 2.88 million (0.34%) were related to viral sequences while 512.63 million (60.5%) and 50.87 million (6%) matched bacterial and eukaryotic sequences, respectively. Among the viral reads, sequences related to mammalian viruses from 13 genera in 10 viral families were identified, including Coronaviridae, Nairoviridae, Paramyxoviridae, Parvoviridae, Polyomaviridae, Papillomaviridae, Astroviridae, Picornaviridae, Poxviridae, and Genomoviridae. Some viral sequences belong to known camel or human viruses and others are from potentially novel camel viruses with only limited sequence similarity to virus sequences in GenBank. A total of five potentially novel virus species or strains were identified. Co-infection of at least two recently identified camel coronaviruses was detected in 92.6% of the camels in the study. This study provides a comprehensive survey of viruses in the virome of upper respiratory samples in camels that have extensive contact with the human population.",2017 Sep 13,"['Li, Yan', 'Khalafalla, Abdelmalik Ibrahim', 'Paden, Clinton R.', 'Yusof, Mohammed F.', 'Eltahir, Yassir M.', 'Al Hammadi, Zulaikha M.', 'Tao, Ying', 'Queen, Krista', 'Hosani, Farida Al', 'Gerber, Susan I.', 'Hall, Aron J.', 'Al Muhairi, Salama', 'Tong, Suxiang']",PLoS One,,,False
64ada09043be47208d892a974b842d4ccb4df356,PMC,"Pandemics, public health emergencies and antimicrobial resistance - putting the threat in an epidemiologic and risk analysis context",http://dx.doi.org/10.1186/s13690-017-0223-7,PMC5597990,28924475,CC BY,"Public health messaging about antimicrobial resistance (AMR) sometimes conveys the problem as an epidemic. We outline why AMR is a serious endemic problem manifested in hospital and community-acquired infections. AMR is not an epidemic condition, but may complicate epidemics, which are characterised by sudden societal impact due to rapid rise in cases over a short timescale. Influenza, which causes direct viral effects, or secondary bacterial complications is the most likely cause of an epidemic or pandemic where AMR may be a problem. We discuss other possible causes of a pandemic with AMR, and present a risk assessment formula to estimate the impact of AMR during a pandemic. Finally, we flag the potential impact of genetic engineering of pathogens on global risk and how this could radically change the epidemiology of AMR as we know it. Understanding the epidemiology of AMR is key to successfully addressing the problem. AMR is an endemic condition but can play a role in epidemics or pandemics, and we present a risk analysis method for assessing the impact of AMR in a pandemic.",2017 Sep 14,"['MacIntyre, C. Raina', 'Bui, Chau Minh']",Arch Public Health,,,True
e523533cb5df819c3354420da60b7c82f9f92485,PMC,Estimating and modelling the transmissibility of Middle East Respiratory Syndrome CoronaVirus during the 2015 outbreak in the Republic of Korea,http://dx.doi.org/10.1111/irv.12467,PMC5598245,28703921,CC BY,"BACKGROUND: Emerging respiratory infections represent a significant public health threat. Because of their novelty, there are limited measures available to control their early spread. Learning from past outbreaks is important for future preparation. The Middle Eastern Respiratory Syndrome CoronaVirus (MERS‐CoV ) 2015 outbreak in the Republic of Korea (ROK) provides one such opportunity. OBJECTIVES: We demonstrated through quantitative methodologies how to estimate MERS‐CoV's transmissibility and identified the effective countermeasures that stopped its spread. METHODS: Using the outbreak data, statistical methods were employed to estimate the basic reproductive number R (0), the average number of secondary cases produced by a typical primary case during its entire infectious period in a fully susceptible population. A transmission dynamics model was also proposed to estimate R (0) and to identify the most effective countermeasures. The consistency between results will provide cross‐validation of the approaches. RESULTS: R (0) ranged from 2.5 with 95% confidence interval (CI): [1.7, 3.1] (using the sequential Bayesian method) to 7.2 with 95% CI: [5.3, 9.4] (using the Nowcasting method). Estimates from transmission model were higher but overlapped with these. Personal protection and rapid confirmation of cases were identified as the most important countermeasures. CONCLUSIONS: Our estimates were in agreement with others from the ROK outbreak, albeit significantly higher than estimates based on other small outbreaks and sporadic cases of MERS‐CoV. The large‐scale outbreak in the ROK was jointly due to the high transmissibility in the healthcare‐associated setting and the Korean culture‐associated contact behaviour. Limiting such behaviour by rapidly identifying and isolating cases and avoiding high‐risk contacts effectively stopped further transmission.",2017 Sep 17,"['Zhang, Xu‐Sheng', 'Pebody, Richard', 'Charlett, Andre', 'de Angelis, Daniela', 'Birrell, Paul', 'Kang, Hunseok', 'Baguelin, Marc', 'Choi, Yoon Hong']",Influenza Other Respir Viruses,,,True
ca0eb068e5fa4d0bdb05c7d5d6a2a0e0fbd36e40,PMC,Nasopharyngeal bacterial load as a marker for rapid and easy diagnosis of invasive pneumococcal disease in children from Mozambique,http://dx.doi.org/10.1371/journal.pone.0184762,PMC5599037,28910402,CC BY,"BACKGROUND: Current diagnostic methods for detection of Streptococcus pneumoniae in children with suspected invasive pneumococcal disease have limitations of accuracy, timeliness, and patient convenience. This study aimed to determine the performance of pneumococcal load quantified with a real-time polymerase-chain reaction in nasopharyngeal samples to diagnose invasive pneumococcal disease in children. METHODS: Matched case-control study of patients <5 years of age with invasive pneumococcal disease admitted to the Manhiça District Hospital (Mozambique) and asymptomatic controls recruited in different periods between 2006 and 2014. Cases were confirmed by a positive bacterial culture for S. pneumoniae in blood or cerebrospinal fluid. Nasopharyngeal aspirates were collected from cases and controls and pneumococcal density was quantified by lytA real-time polymerase-chain reaction. RESULTS: Thirty cases (median age 12.8 months) and sixty controls (median age 11.7 months) were enrolled and 70% of them were male. Nasopharyngeal pneumococcal carriage was high in both groups: 28/30 (93.3%) for cases vs. 53/60 (88.3%) for controls (p = 0.71). Mean nasopharyngeal pneumococcal load was identified as a marker for invasive pneumococcal disease (7.0 log(10) copies/mL in cases vs. 5.8 log(10) copies/mL in controls, p<0.001) and showed good discriminatory power (AUC-ROC: 82.1%, 95% CI 72.5%-91.8%). A colonization density of 6.5 log(10) copies/mL was determined as the optimal cut-off value to distinguish cases from controls (sensitivity 75.0%, specificity 73.6%). CONCLUSION: Use of non-invasive nasopharyngeal aspirates coupled with rapid and accurate quantification of pneumococcal load by real-time polymerase chain reaction has the potential to become a useful surrogate marker for early diagnosis of invasive pneumococcal disease in children.",2017 Sep 14,"['Brotons, Pedro', 'Bassat, Quique', 'Lanaspa, Miguel', 'Henares, Desiree', 'Perez-Arguello, Amaresh', 'Madrid, Lola', 'Balcells, Reyes', 'Acacio, Sozinho', 'Andres-Franch, Maria', 'Marcos, Maria Angeles', 'Valero-Rello, Ana', 'Muñoz-Almagro, Carmen']",PLoS One,,,True
bdb4a76b9add4907c177c780d8318e3256dce7ca,PMC,Analysis of VSV pseudotype virus infection mediated by rubella virus envelope proteins,http://dx.doi.org/10.1038/s41598-017-10865-2,PMC5599607,28912595,CC BY,"Rubella virus (RV) generally causes a systemic infection in humans. Viral cell tropism is a key determinant of viral pathogenesis, but the tropism of RV is currently poorly understood. We analyzed various human cell lines and determined that RV only establishes an infection efficiently in particular non-immune cell lines. To establish an infection the host cells must be susceptible and permissible. To assess the susceptibility of individual cell lines, we generated a pseudotype vesicular stomatitis virus bearing RV envelope proteins (VSV-RV/CE2E1). VSV-RV/CE2E1 entered cells in an RV envelope protein-dependent manner, and thus the infection was neutralized completely by an RV-specific antibody. The infection was Ca(2+)-dependent and inhibited by endosomal acidification inhibitors, further confirming the dependency on RV envelope proteins for the VSV-RV/CE2E1 infection. Human non-immune cell lines were mostly susceptible to VSV-RV/CE2E1, while immune cell lines were much less susceptible than non-immune cell lines. However, susceptibility of immune cells to VSV-RV/CE2E1 was increased upon stimulation of these cells. Our data therefore suggest that immune cells are generally less susceptible to RV infection than non-immune cells, but the susceptibility of immune cells is enhanced upon stimulation.",2017 Sep 14,"['Sakata, Masafumi', 'Tani, Hideki', 'Anraku, Masaki', 'Kataoka, Michiyo', 'Nagata, Noriyo', 'Seki, Fumio', 'Tahara, Maino', 'Otsuki, Noriyuki', 'Okamoto, Kiyoko', 'Takeda, Makoto', 'Mori, Yoshio']",Sci Rep,,,True
4a99bf8fae88d43868e5b8ec0fa4c1c375b951f7,PMC,Stigmatization among people living with HIV in Hong Kong: A qualitative study,http://dx.doi.org/10.1111/hex.12535,PMC5600241,28195685,CC BY,"BACKGROUND: HIV/AIDS is one of the most stigmatized medical conditions across the world. Self‐stigma is prevalent among people living with HIV (PLHIV) and a major obstacle to HIV prevention and care. OBJECTIVE: This study aimed to describe the experiences of stigmatization and explore the possible factors that might be associated with stigmatization among PLHIV in Hong Kong. DESIGN: Qualitative in‐depth interviews were conducted. SETTING AND PARTICIPANTS: 15 PLHIV were recruited from two local non‐governmental organizations on HIV prevention. MAIN VARIABLES STUDIED: Participants were interviewed about their views and feelings towards oneself as a PLHIV and contributing factors, experiences of discriminations, stigmatizing behaviours, issues about disclosure, social relationships and potential impact of HIV. RESULTS AND CONCLUSIONS: Thematic analyses revealed three levels of factors which might be associated with stigmatization: (i) intrapersonal level (misconceptions about HIV, attribution of self‐responsibility, severe state of illness, side‐effects of medication), (ii) interpersonal level (discrimination, social rejection) and (iii) social level (mass media, public stereotypes). Findings provide important insights into which interventions to reduce stigmatization of PLHIV could be designed.",2017 Oct 14,"['Mo, Phoenix K. H.', 'Ng, Charlson T. Y.']",Health Expect,,,True
af98e2fb49846bf4a681883aa16021a372969cb4,PMC,Model of the pathway of −1 frameshifting: Long pausing,http://dx.doi.org/10.1016/j.bbrep.2016.01.017,PMC5600365,28955849,CC BY,"It has been characterized that the programmed ribosomal −1 frameshifting often occurs at the slippery sequence on the presence of a downstream mRNA pseudoknot. In some prokaryotic cases such as the dnaX gene of Escherichia coli, an additional stimulatory signal—an upstream, internal Shine–Dalgarno (SD) sequence—is also necessary to stimulate the efficient −1 frameshifting. However, the molecular and physical mechanism of the −1 frameshifting is poorly understood. Here, we propose a model of the pathway of the −1 translational frameshifting during ribosome translation of the dnaX −1 frameshift mRNA. With the model, the single-molecule fluorescence data (Chen et al. (2014) [29]) on the dynamics of the shunt either to long pausing or to normal translation, the tRNA transit and sampling dynamics in the long-paused rotated state, the EF-G sampling dynamics, the mean rotated-state lifetimes, etc., are explained quantitatively. Moreover, the model is also consistent with the experimental data (Yan et al. (2015) [30]) on translocation excursions and broad branching of frameshifting pathways. In addition, we present some predicted results, which can be easily tested by future optical trapping experiments.",2016 Jan 29,"Xie, Ping",Biochem Biophys Rep,,,False
5e442899227a0032456c65aca20dfa2f6fa6e7fd,PMC,Model of the pathway of −1 frameshifting: Long pausing,http://dx.doi.org/10.1016/j.bbrep.2016.01.017,PMC5600365,28955849,CC BY,"It has been characterized that the programmed ribosomal −1 frameshifting often occurs at the slippery sequence on the presence of a downstream mRNA pseudoknot. In some prokaryotic cases such as the dnaX gene of Escherichia coli, an additional stimulatory signal—an upstream, internal Shine–Dalgarno (SD) sequence—is also necessary to stimulate the efficient −1 frameshifting. However, the molecular and physical mechanism of the −1 frameshifting is poorly understood. Here, we propose a model of the pathway of the −1 translational frameshifting during ribosome translation of the dnaX −1 frameshift mRNA. With the model, the single-molecule fluorescence data (Chen et al. (2014) [29]) on the dynamics of the shunt either to long pausing or to normal translation, the tRNA transit and sampling dynamics in the long-paused rotated state, the EF-G sampling dynamics, the mean rotated-state lifetimes, etc., are explained quantitatively. Moreover, the model is also consistent with the experimental data (Yan et al. (2015) [30]) on translocation excursions and broad branching of frameshifting pathways. In addition, we present some predicted results, which can be easily tested by future optical trapping experiments.",2016 Jan 29,"Xie, Ping",Biochem Biophys Rep,,,False
14ce5ceaf5d2d69b5be566af6122dacd219ce893,PMC,Model of the pathway of −1 frameshifting: Long pausing,http://dx.doi.org/10.1016/j.bbrep.2016.01.017,PMC5600365,28955849,CC BY,"It has been characterized that the programmed ribosomal −1 frameshifting often occurs at the slippery sequence on the presence of a downstream mRNA pseudoknot. In some prokaryotic cases such as the dnaX gene of Escherichia coli, an additional stimulatory signal—an upstream, internal Shine–Dalgarno (SD) sequence—is also necessary to stimulate the efficient −1 frameshifting. However, the molecular and physical mechanism of the −1 frameshifting is poorly understood. Here, we propose a model of the pathway of the −1 translational frameshifting during ribosome translation of the dnaX −1 frameshift mRNA. With the model, the single-molecule fluorescence data (Chen et al. (2014) [29]) on the dynamics of the shunt either to long pausing or to normal translation, the tRNA transit and sampling dynamics in the long-paused rotated state, the EF-G sampling dynamics, the mean rotated-state lifetimes, etc., are explained quantitatively. Moreover, the model is also consistent with the experimental data (Yan et al. (2015) [30]) on translocation excursions and broad branching of frameshifting pathways. In addition, we present some predicted results, which can be easily tested by future optical trapping experiments.",2016 Jan 29,"Xie, Ping",Biochem Biophys Rep,,,False
4c71e5b4d4b332ee8522373d949ceff2bed03718,PMC,Expression and regulation of the neutral amino acid transporter B(0)AT1 in rat small intestine,http://dx.doi.org/10.1371/journal.pone.0184845,PMC5600382,28915252,CC BY,"Absorption of neutral amino acids across the luminal membrane of intestinal enterocytes is mediated by the broad neutral amino acid transporter B(0)AT1 (SLC6A19). Its intestinal expression depends on co-expression of the membrane-anchored peptidase angiotensin converting enzyme 2 (ACE2) and is additionally enhanced by aminopeptidase N (CD13). We investigated in this study the expression of B(0)AT1 and its auxiliary peptidases as well as its transport function along the rat small intestine. Additionally, we tested its possible short- and long-term regulation by dietary proteins and amino acids. We showed by immunofluorescence that B(0)AT1, ACE2 and CD13 co-localize on the luminal membrane of small intestinal villi and by Western blotting that their protein expression increases in distal direction. Furthermore, we observed an elevated transport activity of the neutral amino acid L-isoleucine during the nocturnal active phase compared to the inactive one. Gastric emptying was delayed by intragastric application of an amino acid cocktail but we observed no acute dietary regulation of B(0)AT1 protein expression and L-isoleucine transport. Investigation of the chronic dietary regulation of B(0)AT1, ACE2 and CD13 by different diets revealed an increased B(0)AT1 protein expression under amino acid-supplemented diet in the proximal section but not in the distal one and for ACE2 protein expression a reverse localization of the effect. Dietary regulation for CD13 protein expression was not as distinct as for the two other proteins. Ring uptake experiments showed a tendency for increased L-isoleucine uptake under amino acid-supplemented diet and in vivo L-isoleucine absorption was more efficient under high protein and amino acid-supplemented diet. Additionally, plasma levels of branched-chain amino acids were elevated under high protein and amino acid diet. Taken together, our experiments did not reveal an acute amino acid-induced regulation of B(0)AT1 but revealed a chronic dietary adaptation mainly restricted to the proximal segment of the small intestine.",2017 Sep 15,"['Jando, Julia', 'Camargo, Simone M. R.', 'Herzog, Brigitte', 'Verrey, François']",PLoS One,,,True
f4f0d1b957340175fd951c8fa9c27815dd589f26,PMC,"The inhibitory effect of 7,7″-dimethoxyagastisflavone on the metastasis of melanoma cells via the suppression of F-actin polymerization",http://dx.doi.org/10.18632/oncotarget.10960,PMC5601121,28947953,CC BY,"7,7″-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from Taxus × media cv. Hicksii, induces apoptotic and autophagic cell death. However, whether DMGF suppresses tumor metastasis is unclear. The aim of this study was to investigate the anti-metastatic activities of DMGF on the metastatic processes of melanoma cells in vivo and in vitro. A transwell assay showed that DMGF could effectively attenuate the motility of B16F10 cells, and the results of real-time PCR revealed that DMGF also suppressed the expressions of matrix metalloproteinase-2 (MMP-2). Moreover, DMGF did not influence tube formation but inhibited the migration of endothelial cells. Furthermore, animal models were used to monitor the effects of DMGF on tumor metastasis, and all models showed that DMGF significantly suppressed the metastatic behaviors of B16F10 cells, including intravasation, colonization, and invasion of the lymphatic duct. In addition, DMGF could also reduce the densities of the blood vessels in the tumor area in vivo. Further investigation of the molecular mechanisms of anti-metastatic activity revealed that DMGF can down-regulate the levels of key modulators of the Cdc42/Rac1 pathway to interfere in F-actin polymerization and suppress the formation of lamellipodia by reducing the phosphorylation of CREB. These data suggested that DMGF presents anti-metastatic activities in B16F10 melanoma cells. Here, we demonstrated that DMGF can inhibit the metastasis of highly invasive melanoma cancer cells through the down-regulation of F-actin polymerization. Considering these findings, DMGF may be further developed to serve as a chemoprevention drug for patients with metastatic melanoma.",2016 Jul 30,"['Lin, Ching-Min', 'Lin, Yu-Ling', 'Ho, Shu-Yi', 'Chen, Pin-Rong', 'Tsai, Yi-Hsuan', 'Chung, Chen-Han', 'Hwang, Chia-Hsiang', 'Tsai, Nu-Man', 'Tzou, Shey-Cherng', 'Ke, Chun-Yen', 'Chang, Jung', 'Chan, Yi-Lin', 'Wang, Yu-Shan', 'Chi, Kwan-Hwa', 'Liao, Kuang-Wen']",Oncotarget,,,True
a8cec4aaa782514ef42b320b845e9d2d1804b42d,PMC,Respiratory viral infections are underdiagnosed in patients with suspected sepsis,http://dx.doi.org/10.1007/s10096-017-2990-z,PMC5602075,28516200,CC BY,"The study aim was to investigate the prevalence and clinical relevance of viral findings by multiplex PCR from the nasopharynx of clinically septic patients during a winter season. During 11 weeks of the influenza epidemic period in January–March 2012, consecutive adult patients suspected to be septic (n = 432) were analyzed with cultures from blood and nasopharynx plus multiplex PCR for respiratory viruses on the nasopharyngeal specimen. The results were compared with those from microbiology analyses ordered as part of standard care. During the winter season, viral respiratory pathogens, mainly influenza A virus, human metapneumovirus, coronavirus, and respiratory syncytial virus were clinically underdiagnosed in 70% of patients positive by the multiplex PCR assay. During the first four weeks of the influenza epidemic, few tests for influenza were ordered by clinicians, indicating low awareness that the epidemic had started. Nasopharyngeal findings of Streptococcus pneumoniae and Haemophilus influenzae by culture correlated to pneumonia diagnosis, and in those patients laboratory signs of viral co-infections were common but rarely suspected by clinicians. The role of respiratory viral infections in patients presenting with a clinical picture of sepsis is underestimated. Specific antiviral treatment might be beneficial in some cases and may reduce spread in a hospital setting. Diagnosing viral infections may promote reduction of unnecessary antibiotic use. It can also be a tool for decisions concerning patient logistics, in order to minimize exposure of susceptible patients and personnel. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10096-017-2990-z) contains supplementary material, which is available to authorized users.",2017 May 17,"['Ljungström, L. R.', 'Jacobsson, G.', 'Claesson, B. E. B.', 'Andersson, R.', 'Enroth, H.']",Eur J Clin Microbiol Infect Dis,,,True
b4625acf19fca7b49e058b46f640125fa4e367f5,PMC,Evaluation of NxTAG Respiratory Pathogen Panel and Comparison with xTAG Respiratory Viral Panel Fast v2 and Film Array Respiratory Panel for Detecting Respiratory Pathogens in Nasopharyngeal Aspirates and Swine/Avian-Origin Influenza A Subtypes in Culture Isolates,http://dx.doi.org/10.1155/2017/1324276,PMC5602486,28947901,CC BY,"This study evaluated a new multiplex kit, Luminex NxTAG Respiratory Pathogen Panel, for respiratory pathogens and compared it with xTAG RVP Fast v2 and FilmArray Respiratory Panel using nasopharyngeal aspirate specimens and culture isolates of different swine/avian-origin influenza A subtypes (H2N2, H5N1, H7N9, H5N6, and H9N2). NxTAG RPP gave sensitivity of 95.2%, specificity of 99.6%, PPV of 93.5%, and NPV of 99.7%. NxTAG RPP, xTAG RVP, and FilmArray RP had highly concordant performance among each other for the detection of respiratory pathogens. The mean analytic sensitivity (TCID50/ml) of NxTAG RPP, xTAG RVP, and FilmArray RP for detection of swine/avian-origin influenza A subtype isolates was 0.7, 41.8, and 0.8, respectively. All three multiplex assays correctly typed and genotyped the influenza viruses, except for NxTAG RRP that could not distinguish H3N2 from H3N2v. Further investigation should be performed if H3N2v is suspected to be the cause of disease. Sensitive and specific laboratory diagnosis of all influenza A viruses subtypes is especially essential in certain epidemic regions, such as Southeast Asia. The results of this study should help clinical laboratory professionals to be aware of the different performances of commercially available molecular multiplex RT-PCR assays that are commonly adopted in many clinical diagnostic laboratories.",2017 Aug 29,"['Chan, K. H.', 'To, K. K. W.', 'Li, P. T. W.', 'Wong, T. L.', 'Zhang, R.', 'Chik, K. K. H.', 'Chan, G.', 'Yip, C. C. Y.', 'Chen, H. L.', 'Hung, I. F. N.', 'Chan, J. F. W.', 'Yuen, K. Y.']",Adv Virol,,,True
ebcbb4241c95ad27eced8844b2efa4e450535931,PMC,First Confirmed Case of Middle East Respiratory Syndrome Coronavirus Infection in the Kingdom of Bahrain: In a Saudi Gentleman after Cardiac Bypass Surgery,http://dx.doi.org/10.1155/2017/1262838,PMC5602653,28948054,CC BY,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is well known to cause severe respiratory infection and was first reported in the Kingdom of Saudi Arabia in 2012. We report here the first confirmed MERS-CoV infection in the Kingdom of Bahrain in a Saudi gentleman who was admitted electively for coronary bypass surgery, postoperatively developed an acute respiratory illness, and tested positive for MERS-CoV. 40 close contacts, all healthcare workers, were traced and followed with no documented secondary cases.",2017 Aug 28,"['Seddiq, Nahed', 'Al-Qahtani, Manaf', 'Al-Tawfiq, Jaffar A.', 'Bukamal, Nazar']",Case Rep Infect Dis,,,True
f33491026ec8a7ac58322108f149d5dc9d8dca89,PMC,Deciphering of the Human Interferon-Regulated Proteome by Mass Spectrometry-Based Quantitative Analysis Reveals Extent and Dynamics of Protein Induction and Repression,http://dx.doi.org/10.3389/fimmu.2017.01139,PMC5603615,28959263,CC BY,"Interferons (IFNs) are pleotropic cytokines secreted upon encounter of pathogens and tumors. Applying their antipathogenic, antiproliferative, and immune stimulatory capacities, recombinant IFNs are frequently prescribed as drugs to treat different diseases. IFNs act by changing the gene expression profile of cells. Due to characteristics such as rapid gene induction and signaling, IFNs also represent prototypical model systems for various aspects of biomedical research (e.g., signal transduction). In regard to the signaling and activated promoters, IFNs can be subdivided into two groups. Here, alterations of the cellular proteome of human cells treated with IFNα and IFNγ were elucidated in a time-resolved manner by quantitative proteome analysis. The majority of protein regulations were strongly IFN type and time dependent. In addition to the expected upregulation of IFN-responsive proteins, an astonishing number of proteins became profoundly repressed especially by IFNγ. Thus, our comprehensive analysis revealed important insights into the human IFN-regulated proteome and its dynamics of protein induction and repression. Interestingly, the new class of IFN-repressed genes comprises known host factors for highly relevant pathogens such as HIV, dengue virus, and hepatitis C virus.",2017 Sep 14,"['Megger, Dominik A.', 'Philipp, Jos', 'Le-Trilling, Vu Thuy Khanh', 'Sitek, Barbara', 'Trilling, Mirko']",Front Immunol,,,True
ffcc037270daaf7a3c1869c957f412948e45de17,PMC,Immunological Control of Viral Infections in Bats and the Emergence of Viruses Highly Pathogenic to Humans,http://dx.doi.org/10.3389/fimmu.2017.01098,PMC5604070,28959255,CC BY,"Bats are reservoir hosts of many important viruses that cause substantial disease in humans, including coronaviruses, filoviruses, lyssaviruses, and henipaviruses. Other than the lyssaviruses, they do not appear to cause disease in the reservoir bats, thus an explanation for the dichotomous outcomes of infections of humans and bat reservoirs remains to be determined. Bats appear to have a few unusual features that may account for these differences, including evidence of constitutive interferon (IFN) activation and greater combinatorial diversity in immunoglobulin genes that do not undergo substantial affinity maturation. We propose these features may, in part, account for why bats can host these viruses without disease and how they may contribute to the highly pathogenic nature of bat-borne viruses after spillover into humans. Because of the constitutive IFN activity, bat-borne viruses may be shed at low levels from bat cells. With large naive antibody repertoires, bats may control the limited virus replication without the need for rapid affinity maturation, and this may explain why bats typically have low antibody titers to viruses. However, because bat viruses have evolved in high IFN environments, they have enhanced countermeasures against the IFN response. Thus, upon infection of human cells, where the IFN response is not constitutive, the viruses overwhelm the IFN response, leading to abundant virus replication and pathology.",2017 Sep 11,"['Schountz, Tony', 'Baker, Michelle L.', 'Butler, John', 'Munster, Vincent']",Front Immunol,,,True
b121a4b1dc6d8e513631edeb11421f20aad79106,PMC,Survival of porcine epidemic diarrhea virus (PEDV) in thermally treated feed ingredients and on surfaces,http://dx.doi.org/10.1186/s40813-017-0064-3,PMC5604292,28932412,CC BY,"BACKGROUND: Infection with Porcine Epidemic Diarrhea Virus (PEDV) causes vomiting, diarrhea, and dehydration in young pigs. The virus made its first appearance in the U.S. in 2013, where it caused substantial neonatal mortality and economic losses in the U.S. pork industry. Based on outbreak investigations, it is hypothesized that the virus could be transmitted through contaminated feed or contaminated feed surfaces. This potential risk created a demand for research on the inactivation kinetics of PEDV in different environments. Therefore, the objective of this study was to evaluate the survival of PEDV in 9 different feed ingredients when exposed to 60, 70, 80, and 90 °C, as well as the survival on four different surfaces (galvanized steel, stainless steel, aluminum, and plastic). RESULTS: Overall, there were no differences (P > 0.05) in virus survival among the different feed matrices studied when thermally processed at 60 to 90 °C for 5, 10, 15, or 30 min. However, the time necessary to achieve a one log reduction in virus concentration was less (P < 0.05) when ingredients were exposed to temperatures from 70 °C (3.7 min), 80 °C (2.4 min), and 90 °C (2.3 min) compared with 60 °C (4.4 min). The maximum inactivation level (3.9 log) was achieved when heating all ingredients at 90 °C for 30 min. There were no differences in the amount of time necessary to cause a one log reduction in PEDV concentration among the different surfaces. CONCLUSIONS: The results of this study showed that PEDV survival among the 9 feed ingredients evaluated was not different when exposed to thermal treatments for up to 30 min. However, different combinations of temperature and time resulted in achieving a 3 to 4 log reduction of PEDV in all feed ingredients evaluated. Finally, PEDV survival was similar on galvanized steel, stainless steel, aluminum and plastic.",2017 Sep 19,"['Trudeau, Michaela P.', 'Verma, Harsha', 'Urriola, Pedro E.', 'Sampedro, Fernando', 'Shurson, Gerald C.', 'Goyal, Sagar M.']",Porcine Health Manag,,,True
4bd3a768f65bf203f8ac6e26fc5c82b373c868bd,PMC,The Process of Wrapping Virus Revealed by a Force Tracing Technique and Simulations,http://dx.doi.org/10.1002/advs.201600489,PMC5604396,28932658,CC BY,"Viral entry into the host cell is the first step of virus infection; however, its dynamic process via endocytosis remains largely elusive. Here, the force tracing technique and single particle simulation are combined to investigate the invagination of single human enterovirus 71 (HEV71, a positive single‐stranded RNA virus that is associated with hand, foot, and mouth disease) via cell membranes during its host cell entry. The experimental results reveal that the HEV71 invaginates in membrane vesicles at a force of 58 ± 16 pN, a duration time of 278 ± 68 ms. The simulation further shows that the virus can reach a partially wrapped state very fast, then the upper surface of the virus is covered by the membrane traveling over a long period of time. Combining the experiment with the simulation, the mechanism of membrane wrapping of virus is uncovered, which provides new insights into how the cell is operated to initiate the endocytosis of virus.",2017 Apr 26,"['Pan, Yangang', 'Zhang, Fuxian', 'Zhang, Liuyang', 'Liu, Shuheng', 'Cai, Mingjun', 'Shan, Yuping', 'Wang, Xianqiao', 'Wang, Hanzhong', 'Wang, Hongda']",Adv Sci (Weinh),,,True
b31e3e25fa04d242866652434296925ac784d358,PMC,The Process of Wrapping Virus Revealed by a Force Tracing Technique and Simulations,http://dx.doi.org/10.1002/advs.201600489,PMC5604396,28932658,CC BY,"Viral entry into the host cell is the first step of virus infection; however, its dynamic process via endocytosis remains largely elusive. Here, the force tracing technique and single particle simulation are combined to investigate the invagination of single human enterovirus 71 (HEV71, a positive single‐stranded RNA virus that is associated with hand, foot, and mouth disease) via cell membranes during its host cell entry. The experimental results reveal that the HEV71 invaginates in membrane vesicles at a force of 58 ± 16 pN, a duration time of 278 ± 68 ms. The simulation further shows that the virus can reach a partially wrapped state very fast, then the upper surface of the virus is covered by the membrane traveling over a long period of time. Combining the experiment with the simulation, the mechanism of membrane wrapping of virus is uncovered, which provides new insights into how the cell is operated to initiate the endocytosis of virus.",2017 Apr 26,"['Pan, Yangang', 'Zhang, Fuxian', 'Zhang, Liuyang', 'Liu, Shuheng', 'Cai, Mingjun', 'Shan, Yuping', 'Wang, Xianqiao', 'Wang, Hanzhong', 'Wang, Hongda']",Adv Sci (Weinh),,,False
ffe3b2ad5b565d38aebab45629d4329fe8bf4e02,PMC,A novel Coltivirus-related virus isolated from free-tailed bats from Côte d’Ivoire is able to infect human cells in vitro,http://dx.doi.org/10.1186/s12985-017-0843-0,PMC5604424,28923111,CC BY,"BACKGROUND: Zoonotic transmission events play a major role in the emergence of novel diseases. While such events are virtually impossible to predict, wildlife screening for potential emerging pathogens can be a first step. Driven by recent disease epidemics like severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Ebola, bats have gained special interest as reservoirs of emerging viruses. METHODS: As part of a bigger study investigating pathogens in African bats we screened animals for the presence of known and unknown viruses. RESULTS: We isolated and characterised a novel reovirus from blood of free-tailed bats (Chaereophon aloysiisabaudiae) captured in 2006 in Côte d’Ivoire. The virus showed closest relationship with two human pathogenic viruses, Colorado tick fever virus and Eyach virus, and was able to infect various human cell lines in vitro. CONCLUSION: The study shows the presence of a coltivirus-related virus in bats from Sub-Sahara Africa. Serological studies could help to assess its impact on humans or wildlife health.",2017 Sep 18,"['Weiss, Sabrina', 'Dabrowski, Piotr Wojtek', 'Kurth, Andreas', 'Leendertz, Siv Aina J.', 'Leendertz, Fabian H.']",Virol J,,,True
c28b246499550a272954111f550f0c8d2ac750cd,PMC,"Cetylpyridinium Chloride (CPC) Exhibits Potent, Rapid Activity Against Influenza Viruses in vitro and in vivo",http://dx.doi.org/10.20411/pai.v2i2.200,PMC5605151,28936484,CC BY,"BACKGROUND: There is a continued need for strategies to prevent influenza. While cetylpyridinium chloride (CPC), a broad-spectrum antimicrobial agent, has an extensive antimicrobial spectrum, its ability to affect respiratory viruses has not been studied in detail. OBJECTIVES: Here, we evaluate the ability of CPC to disrupt influenza viruses in vitro and in vivo. METHODS: The virucidal activity of CPC was evaluated against susceptible and oseltamivir- resistant strains of influenza viruses. The effective virucidal concentration (EC) of CPC was determined using a hemagglutination assay and tissue culture infective dose assay. The effect of CPC on viral envelope morphology and ultrastructure was evaluated using transmission electron microscopy (TEM). The ability of influenza virus to develop resistance was evaluated after multiple passaging in sub-inhibitory concentrations of CPC. Finally, the efficacy of CPC in formulation to prevent and treat influenza infection was evaluated using the PR8 murine influenza model. RESULTS: The virucidal effect of CPC occurred within 10 minutes, with mean EC(50) and EC(2log) ranging between 5 to 20 μg/mL, for most strains of influenza tested regardless of type and resistance to oseltamivir. Examinations using TEM showed that CPC disrupted the integrity of the viral envelope and its morphology. Influenza viruses demonstrated no resistance to CPC despite prolonged exposure. Treated mice exhibited significantly increased survival and maintained body weight compared to untreated mice. CONCLUSIONS: The antimicrobial agent CPC possesses virucidal activity against susceptible and resistant strains of influenza virus by targeting and disrupting the viral envelope. Substantial virucidal activity is seen even at very low concentrations of CPC without development of resistance. Moreover, CPC in formulation reduces influenza-associated mortality and morbidity in vivo.",2017 Jun 26,"['Popkin, Daniel L.', 'Zilka, Sarah', 'Dimaano, Matthew', 'Fujioka, Hisashi', 'Rackley, Cristina', 'Salata, Robert', 'Griffith, Alexis', 'Mukherjee, Pranab K.', 'Ghannoum, Mahmoud A.', 'Esper, Frank']",Pathog Immun,,,True
9170d2682a483c1480ce002486cff53e99789484,PMC,The Clinical Significance of FilmArray Respiratory Panel in Diagnosing Community-Acquired Pneumonia,http://dx.doi.org/10.1155/2017/7320859,PMC5606103,29018819,CC BY,"AIM: FilmArray Respiratory Panel (FilmArray RP) test is an emerging diagnostic method in fast detecting multiple respiratory pathogens; the methodology and clinical significance of FilmArray RP in community-acquired pneumonia (CAP) diagnosis were evaluated in this study. METHODS: Specimens from 74 patients with CAP were analyzed and compared using FilmArray RP, traditional multiple PCR assay, bacterial (or fungal) culture, and serological detection. RESULTS: FilmArray RP and multiplex PCR showed 100% coincidence rate in detecting coronaviruses 229E, OC43, HKU1, and NL63, human metapneumovirus, influenza A and B, and parainfluenza viruses (PIV1, PIV2, and PIV4). There were 15 viral specimens tested as disagreement positive results. FilmArray RP had higher detection rate in detecting dual viral and Mycoplasma pneumoniae infection. The positive bacteria (or fungi) were found in 25 specimens. CONCLUSIONS: This study demonstrated the capability of FilmArray RP for simultaneous detection of broad-spectrum respiratory pathogens and potential use in facilitating better patient care.",2017 Sep 6,"['Chen, Huanzhu', 'Weng, Huilan', 'Lin, Meirui', 'He, Ping', 'Li, Yazhen', 'Xie, Qingdong', 'Ke, Changwen', 'Jiao, Xiaoyang']",Biomed Res Int,,,True
b51c9ebdbe84eed97f99e5aebbc0e5e7c4fba9b7,PMC,Intestinal Organoids—Current and Future Applications,http://dx.doi.org/10.3390/vetsci3040031,PMC5606586,29056739,CC BY,"Recent technical advances in the stem cell field have enabled the in vitro generation of complex structures resembling whole organs termed organoids. Most of these approaches employ culture systems that allow stem cell-derived or tissue progenitor cells to self-organize into three-dimensional (3D)-structures. Since organoids can be grown from different species (human, mouse, cat, dog), organs (intestine, kidney, brain, liver), and from patient-derived induced pluripotent stem cells, they create significant prospects for modelling development and diseases, for toxicology and drug discovery studies, and in the field of regenerative medicine. Here, we report on intestinal stem cells, organoid culture, organoid disease modeling, transplantation, specifically covering the current and future uses of this exciting new insight model to the field of veterinary medicine.",2016 Oct 21,"['Meneses, Andre M. C.', 'Schneeberger, Kerstin', 'Kruitwagen, Hedwig S.', 'Penning, Louis C.', 'van Steenbeek, Frank G.', 'Burgener, Iwan A.', 'Spee, Bart']",Vet Sci,,,True
8041d586dc357d38fb7e13f528d400a14ae64b8d,PMC,The Use of Recombinant Feline Interferon Omega Therapy as an Immune-Modulator in Cats Naturally Infected with Feline Immunodeficiency Virus: New Perspectives,http://dx.doi.org/10.3390/vetsci3040032,PMC5606590,29056740,CC BY,"Type I interferons (IFNs) are well-known cytokines that, among their main functions, are key components of the host immune response against viral infections. Due to its immune modulation properties, they are commonly used in the therapeutic approach of various retroviral infections, namely human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV). In HIV infection, it has been shown that IFN therapy limits early viral replication, particularly useful on post-exposure prophylaxis. In veterinary medicine, recombinant feline interferon omega (rFeIFN-ω) was the first interferon licensed for use in cats. Several studies have recently shown that this compound seems to stimulate the innate immunity, decreasing clinical signs and co-infections in naturally FIV-infected cats. More than summarizing the main conclusions about rFeIFN-ω in cats, this review emphasizes the immune-modulation properties of IFN therapy, opening new perspectives for its use in retroviral infections. Either in FIV-infected cats or in HIV individuals, type I IFNs seem to induce an innate immune-modulation and should not be overlooked as a therapeutic option in retroviral infections.",2016 Oct 27,"['Leal, Rodolfo Oliveira', 'Gil, Solange']",Vet Sci,,,True
ed91b54f1a51e6cca478909c62a47c7210a41a31,PMC,A Retrospective Cohort Study of an Outbreak of Cryptosporidiosis among Veterinary Students,http://dx.doi.org/10.3390/vetsci4020029,PMC5606607,29056688,CC BY,"An outbreak of gastrointestinal illness occurred among a cohort of 56 veterinary technology and 100 veterinary science students at Massey University over an eight-week period in 2013. This coincided with calving in New Zealand’s seasonal dairy farming system and a time when calves with diarrhoea are commonly seen by veterinarians. Laboratory and epidemiological investigations were instigated by MidCentral Public Health Service (MCPHS) in conjunction with the Institute of Veterinary, Animal and Biomedical Sciences (IVABS) at Massey University. Eighty students responded to a questionnaire of which 19 met the case definition, a 24% attack rate. Faecal specimens from seven students contained Cryptosporidium oocysts and Cryptosporidium parvum IIa A18G3R1 was identified from one of the specimens. The inferred median incubation period was five days (range 1–12 days). All of the cases were self-limiting, characterized by diarrhoea, abdominal cramps, and in some cases vomiting, headache, and fever. Having contact with calves with diarrhoea was significantly associated with increased adjusted odds of being a case (OR 10.61, 95% CI 1.87–108.29 for one week of contact; OR 55.05, 95% CI 3.80–1931.18 for two weeks of contact). Outbreaks of cryptosporidiosis had occurred previously among veterinary students at Massey University, but the extremely high infectivity of C. parvum resulted in student illness despite enhanced hygiene precautions.",2017 May 24,"['Benschop, Jackie', 'Booker, Christina M.', 'Shadbolt, Tui', 'Weston, Jenny F.']",Vet Sci,,,True
95a69a957cdea565f23167cabf3a322fa72bc3c5,PMC,A simple and rapid identification method for newly emerged porcine Deltacoronavirus with loop-mediated isothermal amplification,http://dx.doi.org/10.1186/s40659-017-0135-6,PMC5607838,28934984,CC BY,"BACKGROUND: Porcine Deltacoronavirus (PDCoV) is a newly emerged enteropathogenic coronavirus that causes diarrhea and mortality in neonatal piglets. PDCoV has spread to many countries around the world, leading to significant economic losses in the pork industry. Therefore, a rapid and sensitive method for detection of PDCoV in clinical samples is urgently needed. RESULTS: In this study, we developed a single-tube one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay specific for nucleocapsid gene to diagnose and monitor PDCoV infections. The detection limit of RT-LAMP assay was 1 × 10(1) copies of PDCoV, which was approximately 100-fold more sensitive than gel-based one-step reverse transcription polymerase chain reaction (RT-PCR). This assay could specifically amplify PDCoV and had no cross amplification with porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine kobuvirus (PKoV), porcine astrovirus (PAstV), porcine reproductive and respiratory syndrome virus (PRRSV), classic swine fever virus (CSFV), and porcine circovirus type 2 (PCV2). By screening a panel of clinical specimens (N = 192), this method presented a similar sensitivity with nested RT-PCR and was 1–2 log more sensitive than conventional RT-PCR in detection of PDCoV. CONCLUSIONS: The RT-LAMP assay established in this study is a potentially valuable tool, especially in low-resource laboratories and filed settings, for a rapid diagnosis, surveillance, and molecular epidemiology investigation of PDCoV infections. To the best of our knowledge, this is the first work for detection of newly emerged PDCoV with LAMP technology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40659-017-0135-6) contains supplementary material, which is available to authorized users.",2017 Sep 21,"['Zhang, Fanfan', 'Ye, Yu', 'Song, Deping', 'Guo, Nannan', 'Peng, Qi', 'Li, Anqi', 'Zhou, Xingrong', 'Chen, Yanjun', 'Zhang, Min', 'Huang, Dongyan', 'Tang, Yuxin']",Biol Res,,,True
80779b91bf8ddc59dc5391db98f6df3dc4bf930c,PMC,Forensic genetics and genomics: Much more than just a human affair,http://dx.doi.org/10.1371/journal.pgen.1006960,PMC5608170,28934201,CC BY,"While traditional forensic genetics has been oriented towards using human DNA in criminal investigation and civil court cases, it currently presents a much wider application range, including not only legal situations sensu stricto but also and, increasingly often, to preemptively avoid judicial processes. Despite some difficulties, current forensic genetics is progressively incorporating the analysis of nonhuman genetic material to a greater extent. The analysis of this material—including other animal species, plants, or microorganisms—is now broadly used, providing ancillary evidence in criminalistics in cases such as animal attacks, trafficking of species, bioterrorism and biocrimes, and identification of fraudulent food composition, among many others. Here, we explore how nonhuman forensic genetics is being revolutionized by the increasing variety of genetic markers, the establishment of faster, less error-burdened and cheaper sequencing technologies, and the emergence and improvement of models, methods, and bioinformatics facilities.",2017 Sep 21,"['Arenas, Miguel', 'Pereira, Filipe', 'Oliveira, Manuela', 'Pinto, Nadia', 'Lopes, Alexandra M.', 'Gomes, Veronica', 'Carracedo, Angel', 'Amorim, Antonio']",PLoS Genet,,,True
b91687f592e473e256027d68359864d22987fd66,PMC,Forensic genetics and genomics: Much more than just a human affair,http://dx.doi.org/10.1371/journal.pgen.1006960,PMC5608170,28934201,CC BY,"While traditional forensic genetics has been oriented towards using human DNA in criminal investigation and civil court cases, it currently presents a much wider application range, including not only legal situations sensu stricto but also and, increasingly often, to preemptively avoid judicial processes. Despite some difficulties, current forensic genetics is progressively incorporating the analysis of nonhuman genetic material to a greater extent. The analysis of this material—including other animal species, plants, or microorganisms—is now broadly used, providing ancillary evidence in criminalistics in cases such as animal attacks, trafficking of species, bioterrorism and biocrimes, and identification of fraudulent food composition, among many others. Here, we explore how nonhuman forensic genetics is being revolutionized by the increasing variety of genetic markers, the establishment of faster, less error-burdened and cheaper sequencing technologies, and the emergence and improvement of models, methods, and bioinformatics facilities.",2017 Sep 21,"['Arenas, Miguel', 'Pereira, Filipe', 'Oliveira, Manuela', 'Pinto, Nadia', 'Lopes, Alexandra M.', 'Gomes, Veronica', 'Carracedo, Angel', 'Amorim, Antonio']",PLoS Genet,,,False
0336910eaa48898999bc9bb81a11254fefdf1810,PMC,Forensic genetics and genomics: Much more than just a human affair,http://dx.doi.org/10.1371/journal.pgen.1006960,PMC5608170,28934201,CC BY,"While traditional forensic genetics has been oriented towards using human DNA in criminal investigation and civil court cases, it currently presents a much wider application range, including not only legal situations sensu stricto but also and, increasingly often, to preemptively avoid judicial processes. Despite some difficulties, current forensic genetics is progressively incorporating the analysis of nonhuman genetic material to a greater extent. The analysis of this material—including other animal species, plants, or microorganisms—is now broadly used, providing ancillary evidence in criminalistics in cases such as animal attacks, trafficking of species, bioterrorism and biocrimes, and identification of fraudulent food composition, among many others. Here, we explore how nonhuman forensic genetics is being revolutionized by the increasing variety of genetic markers, the establishment of faster, less error-burdened and cheaper sequencing technologies, and the emergence and improvement of models, methods, and bioinformatics facilities.",2017 Sep 21,"['Arenas, Miguel', 'Pereira, Filipe', 'Oliveira, Manuela', 'Pinto, Nadia', 'Lopes, Alexandra M.', 'Gomes, Veronica', 'Carracedo, Angel', 'Amorim, Antonio']",PLoS Genet,,,False
359d79257b07cb81eddbcbcc2882bbb43362cfe4,PMC,Forensic genetics and genomics: Much more than just a human affair,http://dx.doi.org/10.1371/journal.pgen.1006960,PMC5608170,28934201,CC BY,"While traditional forensic genetics has been oriented towards using human DNA in criminal investigation and civil court cases, it currently presents a much wider application range, including not only legal situations sensu stricto but also and, increasingly often, to preemptively avoid judicial processes. Despite some difficulties, current forensic genetics is progressively incorporating the analysis of nonhuman genetic material to a greater extent. The analysis of this material—including other animal species, plants, or microorganisms—is now broadly used, providing ancillary evidence in criminalistics in cases such as animal attacks, trafficking of species, bioterrorism and biocrimes, and identification of fraudulent food composition, among many others. Here, we explore how nonhuman forensic genetics is being revolutionized by the increasing variety of genetic markers, the establishment of faster, less error-burdened and cheaper sequencing technologies, and the emergence and improvement of models, methods, and bioinformatics facilities.",2017 Sep 21,"['Arenas, Miguel', 'Pereira, Filipe', 'Oliveira, Manuela', 'Pinto, Nadia', 'Lopes, Alexandra M.', 'Gomes, Veronica', 'Carracedo, Angel', 'Amorim, Antonio']",PLoS Genet,,,True
eecb946b106a94f26a79a964f0160e8e16f79f42,PMC,Community-acquired pneumonia in children — a changing spectrum of disease,http://dx.doi.org/10.1007/s00247-017-3827-8,PMC5608782,29043417,CC BY,"Pneumonia remains the leading cause of death in children outside the neonatal period, despite advances in prevention and management. Over the last 20 years, there has been a substantial decrease in the incidence of childhood pneumonia and pneumonia-associated mortality. New conjugate vaccines against Haemophilus influenzae type b and Streptococcus pneumoniae have contributed to decreases in radiologic, clinical and complicated pneumonia cases and have reduced hospitalization and mortality. The importance of co-infections with multiple pathogens and the predominance of viral-associated disease are emerging. Better access to effective preventative and management strategies is needed in low- and middle-income countries, while new strategies are needed to address the residual burden of disease once these have been implemented.",2017 Sep 21,"['le Roux, David M.', 'Zar, Heather J.']",Pediatr Radiol,,,True
3949a9e9a8c6c26ed1b9aa4bd9b02291dbeefe4a,PMC,Projecting social contact matrices in 152 countries using contact surveys and demographic data,http://dx.doi.org/10.1371/journal.pcbi.1005697,PMC5609774,28898249,CC BY,"Heterogeneities in contact networks have a major effect in determining whether a pathogen can become epidemic or persist at endemic levels. Epidemic models that determine which interventions can successfully prevent an outbreak need to account for social structure and mixing patterns. Contact patterns vary across age and locations (e.g. home, work, and school), and including them as predictors in transmission dynamic models of pathogens that spread socially will improve the models’ realism. Data from population-based contact diaries in eight European countries from the POLYMOD study were projected to 144 other countries using a Bayesian hierarchical model that estimated the proclivity of age-and-location-specific contact patterns for the countries, using Markov chain Monte Carlo simulation. Household level data from the Demographic and Health Surveys for nine lower-income countries and socio-demographic factors from several on-line databases for 152 countries were used to quantify similarity of countries to estimate contact patterns in the home, work, school and other locations for countries for which no contact data are available, accounting for demographic structure, household structure where known, and a variety of metrics including workforce participation and school enrolment. Contacts are highly assortative with age across all countries considered, but pronounced regional differences in the age-specific contacts at home were noticeable, with more inter-generational contacts in Asian countries than in other settings. Moreover, there were variations in contact patterns by location, with work-place contacts being least assortative. These variations led to differences in the effect of social distancing measures in an age structured epidemic model. Contacts have an important role in transmission dynamic models that use contact rates to characterize the spread of contact-transmissible diseases. This study provides estimates of mixing patterns for societies for which contact data such as POLYMOD are not yet available.",2017 Sep 12,"['Prem, Kiesha', 'Cook, Alex R.', 'Jit, Mark']",PLoS Comput Biol,,,True
49f248207549af324c2a114a55cab11b29b4cfc7,PMC,Projecting social contact matrices in 152 countries using contact surveys and demographic data,http://dx.doi.org/10.1371/journal.pcbi.1005697,PMC5609774,28898249,CC BY,"Heterogeneities in contact networks have a major effect in determining whether a pathogen can become epidemic or persist at endemic levels. Epidemic models that determine which interventions can successfully prevent an outbreak need to account for social structure and mixing patterns. Contact patterns vary across age and locations (e.g. home, work, and school), and including them as predictors in transmission dynamic models of pathogens that spread socially will improve the models’ realism. Data from population-based contact diaries in eight European countries from the POLYMOD study were projected to 144 other countries using a Bayesian hierarchical model that estimated the proclivity of age-and-location-specific contact patterns for the countries, using Markov chain Monte Carlo simulation. Household level data from the Demographic and Health Surveys for nine lower-income countries and socio-demographic factors from several on-line databases for 152 countries were used to quantify similarity of countries to estimate contact patterns in the home, work, school and other locations for countries for which no contact data are available, accounting for demographic structure, household structure where known, and a variety of metrics including workforce participation and school enrolment. Contacts are highly assortative with age across all countries considered, but pronounced regional differences in the age-specific contacts at home were noticeable, with more inter-generational contacts in Asian countries than in other settings. Moreover, there were variations in contact patterns by location, with work-place contacts being least assortative. These variations led to differences in the effect of social distancing measures in an age structured epidemic model. Contacts have an important role in transmission dynamic models that use contact rates to characterize the spread of contact-transmissible diseases. This study provides estimates of mixing patterns for societies for which contact data such as POLYMOD are not yet available.",2017 Sep 12,"['Prem, Kiesha', 'Cook, Alex R.', 'Jit, Mark']",PLoS Comput Biol,,,False
7f67490473a643ff59b8ad115149846bc36825ca,PMC,Host genetic background influences diverse neurological responses to viral infection in mice,http://dx.doi.org/10.1038/s41598-017-12477-2,PMC5610195,28939838,CC BY,"Infection by Theiler’s murine encephalomyelitis virus (TMEV) is a model for neurological outcomes caused by virus infection because it leads to diverse neurological conditions in mice, depending on the strain infected. To extend knowledge on the heterogeneous neurological outcomes caused by TMEV and identify new models of human neurological diseases associated with antecedent infections, we analyzed the phenotypic consequences of TMEV infection in the Collaborative Cross (CC) mouse population. We evaluated 5 different CC strains for outcomes of long-term infection (3 months) and acute vs. early chronic infection (7 vs. 28 days post-infection), using neurological and behavioral phenotyping tests and histology. We correlated phenotypic observations with haplotypes of genomic regions previously linked to TMEV susceptibility to test the hypothesis that genomic diversity within CC mice results in variable disease phenotypes in response to TMEV. None of the 5 strains analyzed had a response identical to that of any other CC strain or inbred strain for which prior data are available, indicating that strains of the CC can produce novel models of neurological disease. Thus, CC strains can be a powerful resource for studying how viral infection can cause different neurological outcomes depending on host genetic background.",2017 Sep 22,"['Brinkmeyer-Langford, Candice L.', 'Rech, Raquel', 'Amstalden, Katia', 'Kochan, Kelli J.', 'Hillhouse, Andrew E.', 'Young, Colin', 'Welsh, C. Jane', 'Threadgill, David W.']",Sci Rep,,,True
e981fac56a2168159157612f40eb0f5fa17a6660,PMC,A novel fast vector method for genetic sequence comparison,http://dx.doi.org/10.1038/s41598-017-12493-2,PMC5610321,28939913,CC BY,"With sharp increasing in biological sequences, the traditional sequence alignment methods become unsuitable and infeasible. It motivates a surge of fast alignment-free techniques for sequence analysis. Among these methods, many sorts of feature vector methods are established and applied to reconstruction of species phylogeny. The vectors basically consist of some typical numerical features for certain biological problems. The features may come from the primary sequences, secondary or three dimensional structures of macromolecules. In this study, we propose a novel numerical vector based on only primary sequences of organism to build their phylogeny. Three chemical and physical properties of primary sequences: purine, pyrimidine and keto are also incorporated to the vector. Using each property, we convert the nucleotide sequence into a new sequence consisting of only two kinds of letters. Therefore, three sequences are constructed according to the three properties. For each letter of each sequence we calculate the number of the letter, the average position of the letter and the variation of the position of the letter appearing in the sequence. Tested on several datasets related to mammals, viruses and bacteria, this new tool is fast in speed and accurate for inferring the phylogeny of organisms.",2017 Sep 22,"['Li, Yongkun', 'He, Lily', 'Lucy He, Rong', 'Yau, Stephen S.-T.']",Sci Rep,,,True
67773f5f18353fa2783c550d6c7fc52a2e10d0bc,PMC,A novel fast vector method for genetic sequence comparison,http://dx.doi.org/10.1038/s41598-017-12493-2,PMC5610321,28939913,CC BY,"With sharp increasing in biological sequences, the traditional sequence alignment methods become unsuitable and infeasible. It motivates a surge of fast alignment-free techniques for sequence analysis. Among these methods, many sorts of feature vector methods are established and applied to reconstruction of species phylogeny. The vectors basically consist of some typical numerical features for certain biological problems. The features may come from the primary sequences, secondary or three dimensional structures of macromolecules. In this study, we propose a novel numerical vector based on only primary sequences of organism to build their phylogeny. Three chemical and physical properties of primary sequences: purine, pyrimidine and keto are also incorporated to the vector. Using each property, we convert the nucleotide sequence into a new sequence consisting of only two kinds of letters. Therefore, three sequences are constructed according to the three properties. For each letter of each sequence we calculate the number of the letter, the average position of the letter and the variation of the position of the letter appearing in the sequence. Tested on several datasets related to mammals, viruses and bacteria, this new tool is fast in speed and accurate for inferring the phylogeny of organisms.",2017 Sep 22,"['Li, Yongkun', 'He, Lily', 'Lucy He, Rong', 'Yau, Stephen S.-T.']",Sci Rep,,,True
913a4c390684cea254cbece18764a7bc005badac,PMC,Original Chemical Series of Pyrimidine Biosynthesis Inhibitors That Boost the Antiviral Interferon Response,http://dx.doi.org/10.1128/AAC.00383-17,PMC5610480,28807907,CC BY,"De novo pyrimidine biosynthesis is a key metabolic pathway involved in multiple biosynthetic processes. Here, we identified an original series of 3-(1H-indol-3-yl)-2,3-dihydro-4H-furo[3,2-c]chromen-4-one derivatives as a new class of pyrimidine biosynthesis inhibitors formed by two edge-fused polycyclic moieties. We show that identified compounds exhibit broad-spectrum antiviral activity and immunostimulatory properties, in line with recent reports linking de novo pyrimidine biosynthesis with innate defense mechanisms against viruses. Most importantly, we establish that pyrimidine deprivation can amplify the production of both type I and type III interferons by cells stimulated with retinoic acid-inducible gene 1 (RIG-I) ligands. Altogether, our results further expand the current panel of pyrimidine biosynthesis inhibitors and illustrate how the production of antiviral interferons is tightly coupled to this metabolic pathway. Functional and structural similarities between this new chemical series and dicoumarol, which was reported before to inhibit pyrimidine biosynthesis at the dihydroorotate dehydrogenase (DHODH) step, are discussed.",2017 Sep 22,"['Lucas-Hourani, Marianne', 'Dauzonne, Daniel', 'Munier-Lehmann, Hélène', 'Khiar, Samira', 'Nisole, Sébastien', 'Dairou, Julien', 'Helynck, Olivier', 'Afonso, Philippe V.', 'Tangy, Frédéric', 'Vidalain, Pierre-Olivier']",Antimicrob Agents Chemother,,,True
ac6b3fe26ffb1e6b3b34200c9053a724e81f2d7a,PMC,Original Chemical Series of Pyrimidine Biosynthesis Inhibitors That Boost the Antiviral Interferon Response,http://dx.doi.org/10.1128/AAC.00383-17,PMC5610480,28807907,CC BY,"De novo pyrimidine biosynthesis is a key metabolic pathway involved in multiple biosynthetic processes. Here, we identified an original series of 3-(1H-indol-3-yl)-2,3-dihydro-4H-furo[3,2-c]chromen-4-one derivatives as a new class of pyrimidine biosynthesis inhibitors formed by two edge-fused polycyclic moieties. We show that identified compounds exhibit broad-spectrum antiviral activity and immunostimulatory properties, in line with recent reports linking de novo pyrimidine biosynthesis with innate defense mechanisms against viruses. Most importantly, we establish that pyrimidine deprivation can amplify the production of both type I and type III interferons by cells stimulated with retinoic acid-inducible gene 1 (RIG-I) ligands. Altogether, our results further expand the current panel of pyrimidine biosynthesis inhibitors and illustrate how the production of antiviral interferons is tightly coupled to this metabolic pathway. Functional and structural similarities between this new chemical series and dicoumarol, which was reported before to inhibit pyrimidine biosynthesis at the dihydroorotate dehydrogenase (DHODH) step, are discussed.",2017 Sep 22,"['Lucas-Hourani, Marianne', 'Dauzonne, Daniel', 'Munier-Lehmann, Hélène', 'Khiar, Samira', 'Nisole, Sébastien', 'Dairou, Julien', 'Helynck, Olivier', 'Afonso, Philippe V.', 'Tangy, Frédéric', 'Vidalain, Pierre-Olivier']",Antimicrob Agents Chemother,,,True
22d9a77f7eb015a61ad58babdd9a9a68c29a3176,PMC,Living with Bats: The Case of Ve Golokuati Township in the Volta Region of Ghana,http://dx.doi.org/10.1155/2017/5938934,PMC5610796,29081813,CC BY,"Transmission of zoonotic pathogens from bats to humans through direct and indirect contact with bats raises public apprehension about living close to bats. In the township of Ve Golokuati in Ghana, several “camps” of Epomophorus gambianus roost in fruit trees that provide ecosystems services for residents. This study explored human-bat interaction in the township and the potential risks of disease transmission from bats to humans. Data were derived through questionnaire administration and participatory appraisal approach involving focus group discussions, participatory landscape mapping, and transect walk. The study found that most human activities within the township, such as petty-trading, domestic chores, and children's outdoor recreation, exposed people to bats. Though there have been no reported cases of disease spillover from bats to humans from the perspective of residents and from medical records, respondents whose activities brought them closer to bats within the township were found to be more likely to experience fevers than those who do not interact with bats frequently. The study recommends education of community members about the potential risks involved in human-bat interactions and makes suggestions for reducing the frequent interactions with and exposure to bats by humans.",2017 Sep 10,"['Ayivor, Jesse S.', 'Ohemeng, Fidelia', 'Tweneboah Lawson, Elaine', 'Waldman, Linda', 'Leach, Melissa', 'Ntiamoa-Baidu, Yaa']",J Environ Public Health,,,True
1c2e5c34faa703640900893c58254c63361bd29b,PMC,Vaccinomics Approach for Designing Potential Peptide Vaccine by Targeting Shigella spp. Serine Protease Autotransporter Subfamily Protein SigA,http://dx.doi.org/10.1155/2017/6412353,PMC5610819,29082265,CC BY,"Shigellosis, a bacillary dysentery, is closely associated with diarrhoea in human and causes infection of 165 million people worldwide per year. Casein-degrading serine protease autotransporter of enterobacteriaceae (SPATE) subfamily protein SigA, an outer membrane protein, exerts both cytopathic and enterotoxic effects especially cytopathic to human epithelial cell type-2 (HEp-2) and is shown to be highly immunogenic. In the present study, we have tried to impose the vaccinomics approach for designing a common peptide vaccine candidate against the immunogenic SigA of Shigella spp. At first, 44 SigA proteins from different variants of S. flexneri, S. dysenteriae, S. boydii, and S. sonnei were assessed to find the most antigenic protein. We retrieved 12 peptides based on the highest score for human leukocyte antigen (HLA) supertypes analysed by NetCTL. Initially, these peptides were assessed for the affinity with MHC class I and class II alleles, and four potential core epitopes VTARAGLGY, FHTVTVNTL, HTTWTLTGY, and IELAGTLTL were selected. From these, FHTVTVNTL and IELAGTLTL peptides were shown to have 100% conservancy. Finally, IELAGTLTL was shown to have the highest population coverage (83.86%) among the whole world population. In vivo study of the proposed epitope might contribute to the development of functional and unique widespread vaccine, which might be an operative alleyway to thwart dysentery from the world.",2017 Sep 7,"['Oany, Arafat Rahman', 'Pervin, Tahmina', 'Mia, Mamun', 'Hossain, Motaher', 'Shahnaij, Mohammad', 'Mahmud, Shahin', 'Kibria, K. M. Kaderi']",J Immunol Res,,,True
f63338a20d7b3df2c60068dddfb9086ece7ba5fb,PMC,"Optimization of the Production Process and Characterization of the Yeast-Expressed SARS-CoV Recombinant Receptor-Binding Domain (RBD219-N1), a SARS Vaccine Candidate",http://dx.doi.org/10.1016/j.xphs.2017.04.037,PMC5612335,28456726,CC BY,"From 2002 to 2003, a global pandemic of severe acute respiratory syndrome (SARS) spread to 5 continents and caused 8000 respiratory infections and 800 deaths. To ameliorate the effects of future outbreaks as well as to prepare for biodefense, a process for the production of a recombinant protein vaccine candidate is under development. Previously, we reported the 5 L scale expression and purification of a promising recombinant SARS vaccine candidate, RBD219-N1, the 218–amino acid residue receptor-binding domain (RBD) of SARS coronavirus expressed in yeast–Pichia pastoris X-33. When adjuvanted with aluminum hydroxide, this protein elicited high neutralizing antibody titers and high RBD-specific antibody titers. However, the yield of RBD219-N1 (60 mg RBD219-N1 per liter of fermentation supernatant; 60 mg/L FS) still required improvement to reach our target of >100 mg/L FS. In this study, we optimized the 10 L scale production process and increased the fermentation yield 6- to 7-fold to 400 mg/ L FS with purification recovery >50%. A panel of characterization tests indicated that the process is reproducible and that the purified, tag-free RBD219-N1 protein has high purity and a well-defined structure and is therefore a suitable candidate for production under current Good Manufacturing Practice and future phase-1 clinical trials.",2017 Aug 26,"['Chen, Wen-Hsiang', 'Chag, Shivali M.', 'Poongavanam, Mohan V.', 'Biter, Amadeo B.', 'Ewere, Ebe A.', 'Rezende, Wanderson', 'Seid, Christopher A.', 'Hudspeth, Elissa M.', 'Pollet, Jeroen', 'McAtee, C. Patrick', 'Strych, Ulrich', 'Bottazzi, Maria Elena', 'Hotez, Peter J.']",J Pharm Sci,,,True
a348cf052e162d6156b8179a82058aff4a0af407,PMC,A potent human neutralizing antibody Fc-dependently reduces established HBV infections,http://dx.doi.org/10.7554/eLife.26738,PMC5614562,28949917,CC BY,"Hepatitis B virus (HBV) infection is a major global health problem. Currently-available therapies are ineffective in curing chronic HBV infection. HBV and its satellite hepatitis D virus (HDV) infect hepatocytes via binding of the preS1 domain of its large envelope protein to sodium taurocholate cotransporting polypeptide (NTCP). Here, we developed novel human monoclonal antibodies that block the engagement of preS1 with NTCP and neutralize HBV and HDV with high potency. One antibody, 2H5-A14, functions at picomolar level and exhibited neutralization-activity-mediated prophylactic effects. It also acts therapeutically by eliciting antibody-Fc-dependent immunological effector functions that impose durable suppression of viral infection in HBV-infected mice, resulting in reductions in the levels of the small envelope antigen and viral DNA, with no emergence of escape mutants. Our results illustrate a novel antibody-Fc-dependent approach for HBV treatment and suggest 2H5-A14 as a novel clinical candidate for HBV prevention and treatment of chronic HBV infection.",,"['Li, Dan', 'He, Wenhui', 'Liu, Ximing', 'Zheng, Sanduo', 'Qi, Yonghe', 'Li, Huiyu', 'Mao, Fengfeng', 'Liu, Juan', 'Sun, Yinyan', 'Pan, Lijing', 'Du, Kaixin', 'Ye, Keqiong', 'Li, Wenhui', 'Sui, Jianhua']",eLife.; 6:e26738,,,True
de1c5a16a75d5c28d9e3a9be2e928406fee458e4,PMC,TRIM25 in the Regulation of the Antiviral Innate Immunity,http://dx.doi.org/10.3389/fimmu.2017.01187,PMC5614919,29018447,CC BY,"TRIM25 is an E3 ubiquitin ligase enzyme that is involved in various cellular processes, including regulation of the innate immune response against viruses. TRIM25-mediated ubiquitination of the cytosolic pattern recognition receptor RIG-I is an essential step for initiation of the intracellular antiviral response and has been thoroughly documented. In recent years, however, additional roles of TRIM25 in early innate immunity are emerging, including negative regulation of RIG-I, activation of the melanoma differentiation-associated protein 5–mitochondrial antiviral signaling protein–TRAF6 antiviral axis and modulation of p53 levels and activity. In addition, the ability of TRIM25 to bind RNA may uncover new mechanisms by which this molecule regulates intracellular signaling and/or RNA virus replication.",2017 Sep 22,"['Martín-Vicente, María', 'Medrano, Luz M.', 'Resino, Salvador', 'García-Sastre, Adolfo', 'Martínez, Isidoro']",Front Immunol,,,True
c383b8dedcefbf78e370b0152058176d9219330e,PMC,Transcriptomic Signatures of Tacaribe Virus-Infected Jamaican Fruit Bats,http://dx.doi.org/10.1128/mSphere.00245-17,PMC5615131,28959737,CC BY,"Tacaribe virus (TCRV) is a mammalian arenavirus that was first isolated from artibeus bats in the 1950s. Subsequent experimental infection of Jamaican fruit bats (Artibeus jamaicensis) caused a disease similar to that of naturally infected bats. Although substantial attention has focused on bats as reservoir hosts of viruses that cause human disease, little is known about the interactions between bats and their pathogens. We performed a transcriptome-wide study to illuminate the response of Jamaican fruit bats experimentally infected with TCRV. Differential gene expression analysis of multiple tissues revealed global and organ-specific responses associated with innate antiviral responses, including interferon alpha/beta and Toll-like receptor signaling, activation of complement cascades, and cytokine signaling, among others. Genes encoding proteins involved in adaptive immune responses, such as gamma interferon signaling and costimulation of T cells by the CD28 family, were also altered in response to TCRV infection. Immunoglobulin gene expression was also elevated in the spleens of infected bats, including IgG, IgA, and IgE isotypes. These results indicate an active innate and adaptive immune response to TCRV infection occurred but did not prevent fatal disease. This de novo assembly provides a high-throughput data set of the Jamaican fruit bat and its host response to TCRV infection, which remains a valuable tool to understand the molecular signatures involved in antiviral responses in bats. IMPORTANCE As reservoir hosts of viruses associated with human disease, little is known about the interactions between bats and viruses. Using Jamaican fruit bats infected with Tacaribe virus (TCRV) as a model, we characterized the gene expression responses to infection in different tissues and identified pathways involved with the response to infection. This report is the most detailed gene discovery work in the species to date and the first to describe immune gene expression responses in bats during a pathogenic viral infection.",2017 Sep 27,"['Gerrard, Diana L.', 'Hawkinson, Ann', 'Sherman, Tyler', 'Modahl, Cassandra M.', 'Hume, Gretchen', 'Campbell, Corey L.', 'Schountz, Tony', 'Frietze, Seth']",mSphere,,,True
afa67c34e52aa31421d540d1ea7484f52b3318e2,PMC,Public Health Network Structure and Collaboration Effectiveness during the 2015 MERS Outbreak in South Korea: An Institutional Collective Action Framework,http://dx.doi.org/10.3390/ijerph14091064,PMC5615601,28914780,CC BY,"Following the 2015 Middle East Respiratory Syndrome (MERS) outbreak in South Korea, this research aims to examine the structural effect of public health network explaining collaboration effectiveness, which is defined as joint efforts to improve quality of service provision, cost savings, and coordination. We tested the bonding and bridging effects on collaboration effectiveness during the MERS outbreak response by utilizing an institutional collective action framework. The analysis results of 114 organizations responding during the crisis show a significant association between the bonding effect and the effectiveness of collaboration, as well as a positive association between risk communication in disseminating public health information and the effectiveness of collaboration.",2017 Sep 15,"['Kim, KyungWoo', 'Andrew, Simon A.', 'Jung, Kyujin']",Int J Environ Res Public Health,,,True
a490933d0fb05e92f52ae3ef9f2d31d3384a9539,PMC,Viral inhibitions of PACT-induced RIG-I activation,http://dx.doi.org/10.18632/oncotarget.18928,PMC5617381,28977821,CC BY,,2017 Jul 3,"['Brisse, Morgan', 'Ly, Hinh']",Oncotarget,,,True
6e568297d56de743ad08b1b3c4ef6dc8dc50fb89,PMC,Advancing Point-of-Care (PoC) Testing Using Human Saliva as Liquid Biopsy,http://dx.doi.org/10.3390/diagnostics7030039,PMC5617939,28677648,CC BY,"Salivary diagnostics is an emerging field for the encroachment of point of care technology (PoCT). The necessity of the development of point-of-care (PoC) technology, the potential of saliva, identification and validation of biomarkers through salivary diagnostic toolboxes, and a broad overview of emerging technologies is discussed in this review. Furthermore, novel advanced techniques incorporated in devices for the early detection and diagnosis of several oral and systemic diseases in a non-invasive, easily-monitored, less time consuming, and in a personalised way is explicated. The latest technology detection systems and clinical utilities of saliva as a liquid biopsy, electric field-induced release and measurement (EFIRM), biosensors, smartphone technology, microfluidics, paper-based technology, and how their futuristic perspectives can improve salivary diagnostics and reduce hospital stays by replacing it with chairside screening is also highlighted.",2017 Jul 4,"['Khan, Rabia Sannam', 'Khurshid, Zohaib', 'Yahya Ibrahim Asiri, Faris']",Diagnostics (Basel),,,True
d14958c8c606c6abc9d79a20721582b07f1fd704,PMC,"A Comprehensive Review of Common Bacterial, Parasitic and Viral Zoonoses at the Human-Animal Interface in Egypt",http://dx.doi.org/10.3390/pathogens6030033,PMC5617990,28754024,CC BY,"Egypt has a unique geographical location connecting the three old-world continents Africa, Asia and Europe. It is the country with the highest population density in the Middle East, Northern Africa and the Mediterranean basin. This review summarizes the prevalence, reservoirs, sources of human infection and control regimes of common bacterial, parasitic and viral zoonoses in animals and humans in Egypt. There is a gap of knowledge conerning the epidemiology of zoonotic diseases at the human-animal interface in different localities in Egypt. Some zoonotic agents are “exotic” for Egypt (e.g., MERS-CoV and Crimean-Congo hemorrhagic fever virus), others are endemic (e.g., Brucellosis, Schistosomiasis and Avian influenza). Transboundary transmission of emerging pathogens from and to Egypt occurred via different routes, mainly importation/exportation of apparently healthy animals or migratory birds. Control of the infectious agents and multidrug resistant bacteria in the veterinary sector is on the frontline for infection control in humans. The implementation of control programs significantly decreased the prevalence of some zoonoses, such as schistosomiasis and fascioliasis, in some localities within the country. Sustainable awareness, education and training targeting groups at high risk (veterinarians, farmers, abattoir workers, nurses, etc.) are important to lessen the burden of zoonotic diseases among Egyptians. There is an urgent need for collaborative surveillance and intervention plans for the control of these diseases in Egypt.",2017 Jul 21,"['Helmy, Yosra A.', 'El-Adawy, Hosny', 'Abdelwhab, Elsayed M.']",Pathogens,,,True
aeb63d391feee1b548adf8d5a208d70c3ee5c802,PMC,Opposite Roles of RNase and Kinase Activities of Inositol-Requiring Enzyme 1 (IRE1) on HSV-1 Replication,http://dx.doi.org/10.3390/v9090235,PMC5618002,28832521,CC BY,"In response to the endoplasmic reticulum (ER) stress induced by herpes simplex virus type 1 (HSV-1) infection, host cells activate the unfolded protein response (UPR) to reduce the protein-folding burden in the ER. The regulation of UPR upon HSV-1 infection is complex, and the downstream effectors can be detrimental to viral replication. Therefore, HSV-1 copes with the UPR to create a beneficial environment for its replication. UPR has three branches, including protein kinase RNA (PKR)-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activated transcription factor 6 (ATF6). IRE1α is the most conserved branch of UPR which has both RNase and kinase activities. Previous studies have shown that IRE1α RNase activity was inactivated during HSV-1 infection. However, the effect of the two activities of IRE1α on HSV-1 replication remains unknown. Results in this study showed that IRE1α expression was up-regulated during HSV-1 infection. We found that in HEC-1-A cells, increasing RNase activity, or inhibiting kinase activity of IRE1α led to viral suppression, indicating that the kinase activity of IRE1α was beneficial, while the RNase activity was detrimental to viral replication. Further evidence showed that the kinase activity of IRE1α leads to the activation of the JNK (c-Jun N-terminal kinases) pathway, which enhances viral replication. Taken together, our evidence suggests that IRE1α is involved in HSV-1 replication, and its RNase and kinase activities play differential roles during viral infection.",2017 Aug 23,"['Su, Airong', 'Wang, Huanru', 'Li, Yanlei', 'Wang, Xiaohui', 'Chen, Deyan', 'Wu, Zhiwei']",Viruses,,,True
b68fe34a76c39bdb20edbdd98829918716d0bcec,PMC,Opposite Roles of RNase and Kinase Activities of Inositol-Requiring Enzyme 1 (IRE1) on HSV-1 Replication,http://dx.doi.org/10.3390/v9090235,PMC5618002,28832521,CC BY,"In response to the endoplasmic reticulum (ER) stress induced by herpes simplex virus type 1 (HSV-1) infection, host cells activate the unfolded protein response (UPR) to reduce the protein-folding burden in the ER. The regulation of UPR upon HSV-1 infection is complex, and the downstream effectors can be detrimental to viral replication. Therefore, HSV-1 copes with the UPR to create a beneficial environment for its replication. UPR has three branches, including protein kinase RNA (PKR)-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activated transcription factor 6 (ATF6). IRE1α is the most conserved branch of UPR which has both RNase and kinase activities. Previous studies have shown that IRE1α RNase activity was inactivated during HSV-1 infection. However, the effect of the two activities of IRE1α on HSV-1 replication remains unknown. Results in this study showed that IRE1α expression was up-regulated during HSV-1 infection. We found that in HEC-1-A cells, increasing RNase activity, or inhibiting kinase activity of IRE1α led to viral suppression, indicating that the kinase activity of IRE1α was beneficial, while the RNase activity was detrimental to viral replication. Further evidence showed that the kinase activity of IRE1α leads to the activation of the JNK (c-Jun N-terminal kinases) pathway, which enhances viral replication. Taken together, our evidence suggests that IRE1α is involved in HSV-1 replication, and its RNase and kinase activities play differential roles during viral infection.",2017 Aug 23,"['Su, Airong', 'Wang, Huanru', 'Li, Yanlei', 'Wang, Xiaohui', 'Chen, Deyan', 'Wu, Zhiwei']",Viruses,,,False
96759aa0dce56dd50709ab124ae0255e0cad79d4,PMC,Ultrastructural Characterization of Membrane Rearrangements Induced by Porcine Epidemic Diarrhea Virus Infection,http://dx.doi.org/10.3390/v9090251,PMC5618017,28872588,CC BY,"The porcine epidemic diarrhea virus (PEDV) is a coronavirus (CoV) belonging to the α-CoV genus and it causes high mortality in infected sucking piglets, resulting in substantial losses in the farming industry. CoV trigger a drastic reorganization of host cell membranes to promote their replication and egression, but a detailed description of the intracellular remodeling induced by PEDV is still missing. In this study, we examined qualitatively and quantitatively, using electron microscopy, the intracellular membrane reorganization induced by PEDV over the course of an infection. With our ultrastructural approach, we reveal that, as most of CoV, PEDV initially forms double-membrane vesicles (DMVs) and convoluted membranes (CMs), which probably serve as replication/transcription platforms. Interestingly, we also found that viral particles start to form almost simultaneously in both the endoplasmic reticulum and the large virion-containing vacuoles (LVCVs), which are compartments originating from the Golgi, confirming that α-CoV assemble indistinguishably in two different organelles of the secretory pathway. Moreover, PEDV virons appear to have an immature and a mature form, similar to another α-CoV the transmissible gastroenteritis coronavirus (TGEV). Altogether, our study underlies the similarities and differences between the lifecycle of α-CoV and that of viruses belonging to other CoV subfamilies.",2017 Sep 5,"['Zhou, Xingdong', 'Cong, Yingying', 'Veenendaal, Tineke', 'Klumperman, Judith', 'Shi, Dongfang', 'Mari, Muriel', 'Reggiori, Fulvio']",Viruses,,,True
dc180c51f54487e4bbbd129c1cc2e30deacd3181,PMC,Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.3390/v9090255,PMC5618021,28906430,CC BY,"The Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012, and circulated worldwide with high mortality. The continual outbreaks of MERS-CoV highlight the importance of developing antiviral therapeutics. Here, we rationally designed a novel fusion inhibitor named MERS-five-helix bundle (MERS-5HB) derived from the six-helix bundle (MERS-6HB) which was formed by the process of membrane fusion. MERS-5HB consists of three copies of heptad repeat 1 (HR1) and two copies of heptad repeat 2 (HR2) while MERS-6HB includes three copies each of HR1 and HR2. As it lacks one HR2, MERS-5HB was expected to interact with viral HR2 to interrupt the fusion step. What we found was that MERS-5HB could bind to HR2P, a peptide derived from HR2, with a strong affinity value (K(D)) of up to 0.24 nM. Subsequent assays indicated that MERS-5HB could inhibit pseudotyped MERS-CoV entry effectively with 50% inhibitory concentration (IC(50)) of about 1 μM. In addition, MERS-5HB significantly inhibited spike (S) glycoprotein-mediated syncytial formation in a dose-dependent manner. Further biophysical characterization showed that MERS-5HB was a thermo-stable α-helical secondary structure. The inhibitory potency of MERS-5HB may provide an attractive basis for identification of a novel inhibitor against MERS-CoV, as a potential antiviral agent.",2017 Sep 14,"['Sun, Yaping', 'Zhang, Huaidong', 'Shi, Jian', 'Zhang, Zhe', 'Gong, Rui']",Viruses,,,True
c6fa41b3711b116f3c39583812a0088793388395,PMC,PERK Signal-Modulated Protein Translation Promotes the Survivability of Dengue 2 Virus-Infected Mosquito Cells and Extends Viral Replication,http://dx.doi.org/10.3390/v9090262,PMC5618028,28930151,CC BY,"Survival of mosquitoes from dengue virus (DENV) infection is a prerequisite of viral transmission to the host. This study aimed to see how mosquito cells can survive the infection during prosperous replication of the virus. In C6/36 cells, global protein translation was shut down after infection by DENV type 2 (DENV2). However, it returned to a normal level when infected cells were treated with an inhibitor of the protein kinase RNA (PKR)-like ER kinase (PERK) signaling pathway. Based on a 7-Methylguanosine 5′-triphosphate (m7GTP) pull-down assay, the eukaryotic translation initiation factor 4F (eIF4F) complex was also identified in DENV2-infected cells. This suggests that most mosquito proteins are synthesized via canonical cap-dependent translation. When the PERK signal pathway was inhibited, both accumulation of reactive oxygen species and changes in the mitochondrial membrane potential increased. This suggested that ER stress response was alleviated through the PERK-mediated shutdown of global proteins in DENV2-infected C6/36 cells. In the meantime, the activities of caspases-9 and -3 and the apoptosis-related cell death rate increased in C6/36 cells with PERK inhibition. This reflected that the PERK-signaling pathway is involved in determining cell survival, presumably by reducing DENV2-induced ER stress. Looking at the PERK downstream target, α-subunit of eukaryotic initiation factor 2 (eIF2α), an increased phosphorylation status was only shown in infected C6/36 cells. This indicated that recruitment of ribosome binding to the mRNA 5′-cap structure could have been impaired in cap-dependent translation. It turned out that shutdown of cellular protein translation resulted in a pro-survival effect on mosquito cells in response to DENV2 infection. As synthesis of viral proteins was not affected by the PERK signal pathway, an alternate mode other than cap-dependent translation may be utilized. This finding provides insights into elucidating how the PERK signal pathway modulates dynamic translation of proteins and helps mosquito cells survive continuous replication of the DENV2. It was ecologically important for virus amplification in mosquitoes and transmission to humans.",2017 Sep 20,"['Hou, Jiun-Nan', 'Chen, Tien-Huang', 'Chiang, Yi-Hsuan', 'Peng, Jing-Yun', 'Yang, Tsong-Han', 'Cheng, Chih-Chieh', 'Sofiyatun, Eny', 'Chiu, Cheng-Hsun', 'Chiang-Ni, Chuan', 'Chen, Wei-June']",Viruses,,,True
2fd204815cb815a2bb96e92174a65e40e04f9afb,PMC,PERK Signal-Modulated Protein Translation Promotes the Survivability of Dengue 2 Virus-Infected Mosquito Cells and Extends Viral Replication,http://dx.doi.org/10.3390/v9090262,PMC5618028,28930151,CC BY,"Survival of mosquitoes from dengue virus (DENV) infection is a prerequisite of viral transmission to the host. This study aimed to see how mosquito cells can survive the infection during prosperous replication of the virus. In C6/36 cells, global protein translation was shut down after infection by DENV type 2 (DENV2). However, it returned to a normal level when infected cells were treated with an inhibitor of the protein kinase RNA (PKR)-like ER kinase (PERK) signaling pathway. Based on a 7-Methylguanosine 5′-triphosphate (m7GTP) pull-down assay, the eukaryotic translation initiation factor 4F (eIF4F) complex was also identified in DENV2-infected cells. This suggests that most mosquito proteins are synthesized via canonical cap-dependent translation. When the PERK signal pathway was inhibited, both accumulation of reactive oxygen species and changes in the mitochondrial membrane potential increased. This suggested that ER stress response was alleviated through the PERK-mediated shutdown of global proteins in DENV2-infected C6/36 cells. In the meantime, the activities of caspases-9 and -3 and the apoptosis-related cell death rate increased in C6/36 cells with PERK inhibition. This reflected that the PERK-signaling pathway is involved in determining cell survival, presumably by reducing DENV2-induced ER stress. Looking at the PERK downstream target, α-subunit of eukaryotic initiation factor 2 (eIF2α), an increased phosphorylation status was only shown in infected C6/36 cells. This indicated that recruitment of ribosome binding to the mRNA 5′-cap structure could have been impaired in cap-dependent translation. It turned out that shutdown of cellular protein translation resulted in a pro-survival effect on mosquito cells in response to DENV2 infection. As synthesis of viral proteins was not affected by the PERK signal pathway, an alternate mode other than cap-dependent translation may be utilized. This finding provides insights into elucidating how the PERK signal pathway modulates dynamic translation of proteins and helps mosquito cells survive continuous replication of the DENV2. It was ecologically important for virus amplification in mosquitoes and transmission to humans.",2017 Sep 20,"['Hou, Jiun-Nan', 'Chen, Tien-Huang', 'Chiang, Yi-Hsuan', 'Peng, Jing-Yun', 'Yang, Tsong-Han', 'Cheng, Chih-Chieh', 'Sofiyatun, Eny', 'Chiu, Cheng-Hsun', 'Chiang-Ni, Chuan', 'Chen, Wei-June']",Viruses,,,False
e98c156b8632c84d14cfb03a1614b36563479bed,PMC,Plant Virus Expression Vectors: A Powerhouse for Global Health,http://dx.doi.org/10.3390/biomedicines5030044,PMC5618302,28758953,CC BY,"Plant-made biopharmaceuticals have long been considered a promising technology for providing inexpensive and efficacious medicines for developing countries, as well as for combating pandemic infectious diseases and for use in personalized medicine. Plant virus expression vectors produce high levels of pharmaceutical proteins within a very short time period. Recently, plant viruses have been employed as nanoparticles for novel forms of cancer treatment. This review provides a glimpse into the development of plant virus expression systems both for pharmaceutical production as well as for immunotherapy.",2017 Jul 30,"Hefferon, Kathleen",Biomedicines,,,True
36b168d717a2816e60feb1b2b833cd0f02163cef,PMC,Rationally designed ligand‐independent peptide inhibitors of TREM‐1 ameliorate collagen‐induced arthritis,http://dx.doi.org/10.1111/jcmm.13173,PMC5618672,28382703,CC BY,"Triggering receptor expressed on myeloid cells 1 (TREM‐1) is critically involved in the pathogenesis of rheumatoid arthritis (RA). In contrast to cytokine blockers, therapeutic blockade of TREM‐1 can blunt excessive inflammation while preserving the capacity for microbial control. However, the nature of the TREM‐1 ligand(s) and mechanisms of TREM‐1 signalling are still not yet well understood, impeding the development of clinically relevant inhibitors of TREM‐1. The aim of this study was to evaluate the anti‐arthritic activity of a novel, ligand‐independent TREM‐1 inhibitory nonapeptide GF9 that was rationally designed using the signalling chain homo oligomerization (SCHOOL) model of cell signalling. Free GF9 and GF9 bound to macrophage‐targeted nanoparticles that mimic human high‐density lipoproteins (GF9‐HDL) were used to treat collagen‐induced arthritis (CIA). We also tested if 31‐mer peptides with sequences from GF9 and helices 4 (GE31) and 6 (GA31) of the major HDL protein, apolipoprotein A‐I, are able to perform three functions: assist in the self‐assembly of GA/E31‐HDL, target these particles to macrophages and block TREM‐1 signalling. We showed that GF9, but not control peptide, ameliorated CIA and protected against bone and cartilage damage. The therapeutic effect of GF9 was accompanied by a reduction in the plasma levels of macrophage colony‐stimulating factor and pro‐inflammatory cytokines such as tumour necrosis factor‐α, interleukin (IL)‐1 and IL‐6. Incorporation of GF9 alone or as a part of GE31 and GA31 peptides into HDL significantly increased its therapeutic efficacy. Collectively, our findings suggest that TREM‐1 inhibitory SCHOOL sequences may be promising alternatives for the treatment of RA.",2017 Oct 6,"['Shen, Zu T.', 'Sigalov, Alexander B.']",J Cell Mol Med,,,True
63a0d9767212d4316c91660dc4eedc8cb3fe527f,PMC,Dihydroberberine exhibits synergistic effects with sunitinib on NSCLC NCI‐H460 cells by repressing MAP kinase pathways and inflammatory mediators,http://dx.doi.org/10.1111/jcmm.13178,PMC5618684,28444871,CC BY,"Highly effective and attenuated dose schedules are good regimens for drug research and development. Combination chemotherapy is a good strategy in cancer therapy. We evaluated the antitumour effects of dihydroberberine combined with sunitinib (DCS) on the human non‐small cell lung cancer cell lines (NSCLC), A549, NCI‐H460, and NCI‐H1299 in vitro and in vivo. DCS showed synergic effects on NCI‐H460 cell proliferation, colony formation and transplantable tumour growth, which suggested dihydroberberine increases the sensitivity of lung carcinoma to sunitinib. Further studies indicated that DCS down‐regulated phosphorylation of JNK, p38, and NF‐κB in NCI‐H460 cells and tumours and suppressed the IκB and COX‐2 expression. In addition, DCS reduced the secretion of the pro‐inflammatory cytokine, interleukin‐1 (IL‐1), in tumours. Inhibition of p38 activation by DCS was a likely contributing factor in IL‐1 and COX‐2 down‐regulation. Consistent with these results, a genomewide microarray analysis found that DCS induced the expression of cell cycle signal molecules that are known to be affected by JNK and p38. The change of cell cycle, in turn, led to down‐regulation of JNK and p38, and further reduced IL‐1 secretion. Collectively, these findings highlight potential molecular mechanisms of DCS chemotherapeutic activity and suggest that DCS is an efficacious strategy in NSCLC therapy.",2017 Oct 26,"['Dai, Bingling', 'Ma, Yujiao', 'Wang, Wenjie', 'Zhan, Yingzhuan', 'Zhang, Dongdong', 'Liu, Rui', 'Zhang, Yanmin']",J Cell Mol Med,,,True
736d5109d55feed08b21d5b95eff52f2e50eea59,PMC,Interference with the production of infectious viral particles and bimodal inhibition of replication are broadly conserved antiviral properties of IFITMs,http://dx.doi.org/10.1371/journal.ppat.1006610,PMC5619827,28957419,CC BY,"IFITMs are broad antiviral factors that block incoming virions in endosomal vesicles, protecting target cells from infection. In the case of HIV-1, we and others reported the existence of an additional antiviral mechanism through which IFITMs lead to the production of virions of reduced infectivity. However, whether this second mechanism of inhibition is unique to HIV or extends to other viruses is currently unknown. To address this question, we have analyzed the susceptibility of a broad spectrum of viruses to the negative imprinting of the virion particles infectivity by IFITMs. The results we have gathered indicate that this second antiviral property of IFITMs extends well beyond HIV and we were able to identify viruses susceptible to the three IFITMs altogether (HIV-1, SIV, MLV, MPMV, VSV, MeV, EBOV, WNV), as well as viruses that displayed a member-specific susceptibility (EBV, DUGV), or were resistant to all IFITMs (HCV, RVFV, MOPV, AAV). The swapping of genetic elements between resistant and susceptible viruses allowed us to point to specificities in the viral mode of assembly, rather than glycoproteins as dominant factors of susceptibility. However, we also show that, contrarily to X4-, R5-tropic HIV-1 envelopes confer resistance against IFITM3, suggesting that viral receptors add an additional layer of complexity in the IFITMs-HIV interplay. Lastly, we show that the overall antiviral effects ascribed to IFITMs during spreading infections, are the result of a bimodal inhibition in which IFITMs act both by protecting target cells from incoming viruses and in driving the production of virions of reduced infectivity. Overall, our study reports for the first time that the negative imprinting of the virion particles infectivity is a conserved antiviral property of IFITMs and establishes IFITMs as a paradigm of restriction factor capable of interfering with two distinct phases of a virus life cycle.",2017 Sep 28,"['Tartour, Kevin', 'Nguyen, Xuan-Nhi', 'Appourchaux, Romain', 'Assil, Sonia', 'Barateau, Véronique', 'Bloyet, Louis-Marie', 'Burlaud Gaillard, Julien', 'Confort, Marie-Pierre', 'Escudero-Perez, Beatriz', 'Gruffat, Henri', 'Hong, Saw See', 'Moroso, Marie', 'Reynard, Olivier', 'Reynard, Stéphanie', 'Decembre, Elodie', 'Ftaich, Najate', 'Rossi, Axel', 'Wu, Nannan', 'Arnaud, Frédérick', 'Baize, Sylvain', 'Dreux, Marlène', 'Gerlier, Denis', 'Paranhos-Baccala, Glaucia', 'Volchkov, Viktor', 'Roingeard, Philippe', 'Cimarelli, Andrea']",PLoS Pathog,,,True
9786f61a3f8175ac0619b3c0d9910e1ec06fa182,PMC,Interference with the production of infectious viral particles and bimodal inhibition of replication are broadly conserved antiviral properties of IFITMs,http://dx.doi.org/10.1371/journal.ppat.1006610,PMC5619827,28957419,CC BY,"IFITMs are broad antiviral factors that block incoming virions in endosomal vesicles, protecting target cells from infection. In the case of HIV-1, we and others reported the existence of an additional antiviral mechanism through which IFITMs lead to the production of virions of reduced infectivity. However, whether this second mechanism of inhibition is unique to HIV or extends to other viruses is currently unknown. To address this question, we have analyzed the susceptibility of a broad spectrum of viruses to the negative imprinting of the virion particles infectivity by IFITMs. The results we have gathered indicate that this second antiviral property of IFITMs extends well beyond HIV and we were able to identify viruses susceptible to the three IFITMs altogether (HIV-1, SIV, MLV, MPMV, VSV, MeV, EBOV, WNV), as well as viruses that displayed a member-specific susceptibility (EBV, DUGV), or were resistant to all IFITMs (HCV, RVFV, MOPV, AAV). The swapping of genetic elements between resistant and susceptible viruses allowed us to point to specificities in the viral mode of assembly, rather than glycoproteins as dominant factors of susceptibility. However, we also show that, contrarily to X4-, R5-tropic HIV-1 envelopes confer resistance against IFITM3, suggesting that viral receptors add an additional layer of complexity in the IFITMs-HIV interplay. Lastly, we show that the overall antiviral effects ascribed to IFITMs during spreading infections, are the result of a bimodal inhibition in which IFITMs act both by protecting target cells from incoming viruses and in driving the production of virions of reduced infectivity. Overall, our study reports for the first time that the negative imprinting of the virion particles infectivity is a conserved antiviral property of IFITMs and establishes IFITMs as a paradigm of restriction factor capable of interfering with two distinct phases of a virus life cycle.",2017 Sep 28,"['Tartour, Kevin', 'Nguyen, Xuan-Nhi', 'Appourchaux, Romain', 'Assil, Sonia', 'Barateau, Véronique', 'Bloyet, Louis-Marie', 'Burlaud Gaillard, Julien', 'Confort, Marie-Pierre', 'Escudero-Perez, Beatriz', 'Gruffat, Henri', 'Hong, Saw See', 'Moroso, Marie', 'Reynard, Olivier', 'Reynard, Stéphanie', 'Decembre, Elodie', 'Ftaich, Najate', 'Rossi, Axel', 'Wu, Nannan', 'Arnaud, Frédérick', 'Baize, Sylvain', 'Dreux, Marlène', 'Gerlier, Denis', 'Paranhos-Baccala, Glaucia', 'Volchkov, Viktor', 'Roingeard, Philippe', 'Cimarelli, Andrea']",PLoS Pathog,,,False
5adc4dd51a8d7dfe7e252c55e8bac9bcc108143a,PMC,The Central Conserved Region (CCR) of Respiratory Syncytial Virus (RSV) G Protein Modulates Host miRNA Expression and Alters the Cellular Response to Infection,http://dx.doi.org/10.3390/vaccines5030016,PMC5620547,28671606,CC BY,"Respiratory Syncytial Virus (RSV) infects respiratory epithelial cells and deregulates host gene expression by many mechanisms including expression of RSV G protein (RSV G). RSV G protein encodes a central conserved region (CCR) containing a CX3C motif that functions as a fractalkine mimic. Disruption of the CX3C motif (a.a. 182–186) located in the CCR of the G protein has been shown to affect G protein function in vitro and the severity of RSV disease pathogenesis in vivo. We show that infection of polarized Calu3 respiratory cells with recombinant RSV having point mutations in Cys173 and 176 (C173/176S) (rA2-GC12), or Cys186 (C186S) (rA2-GC4) is associated with a decline in the integrity of polarized Calu-3 cultures and decreased virus production. This is accompanied with downregulation of miRNAs let-7f and miR-24 and upregulation of interferon lambda (IFNλ), a primary antiviral cytokine for RSV in rA2-GC12/rA2-GC4 infected cells. These results suggest that residues in the cysteine noose region of RSV G protein can modulate IFN λ expression accompanied by downregulation of miRNAs, and are important for RSV G protein function and targeting.",2017 Jul 3,"['Bakre, Abhijeet A.', 'Harcourt, Jennifer L.', 'Haynes, Lia M.', 'Anderson, Larry J.', 'Tripp, Ralph A.']",Vaccines (Basel),,,True
543eecd34daf0351160934011c8da277b883b56c,PMC,The TRIMendous Role of TRIMs in Virus–Host Interactions,http://dx.doi.org/10.3390/vaccines5030023,PMC5620554,28829373,CC BY,"The innate antiviral response is integral in protecting the host against virus infection. Many proteins regulate these signaling pathways including ubiquitin enzymes. The ubiquitin-activating (E1), -conjugating (E2), and -ligating (E3) enzymes work together to link ubiquitin, a small protein, onto other ubiquitin molecules or target proteins to mediate various effector functions. The tripartite motif (TRIM) protein family is a group of E3 ligases implicated in the regulation of a variety of cellular functions including cell cycle progression, autophagy, and innate immunity. Many antiviral signaling pathways, including type-I interferon and NF-κB, are TRIM-regulated, thus influencing the course of infection. Additionally, several TRIMs directly restrict viral replication either through proteasome-mediated degradation of viral proteins or by interfering with different steps of the viral replication cycle. In addition, new studies suggest that TRIMs can exert their effector functions via the synthesis of unconventional polyubiquitin chains, including unanchored (non-covalently attached) polyubiquitin chains. TRIM-conferred viral inhibition has selected for viruses that encode direct and indirect TRIM antagonists. Furthermore, new evidence suggests that the same antagonists encoded by viruses may hijack TRIM proteins to directly promote virus replication. Here, we describe numerous virus–TRIM interactions and novel roles of TRIMs during virus infections.",2017 Aug 22,"['van Tol, Sarah', 'Hage, Adam', 'Giraldo, Maria Isabel', 'Bharaj, Preeti', 'Rajsbaum, Ricardo']",Vaccines (Basel),,,True
2e8855a1b4fa41526eac0e93264c024aef7f6c9d,PMC,Risk factors for multidrug-resistant pathogens in bronchiectasis exacerbations,http://dx.doi.org/10.1186/s12879-017-2754-5,PMC5622549,28964261,CC BY,"BACKGROUND: Non-cystic fibrosis bronchiectasis is a chronic structural lung condition that courses with recurrent infectious exacerbations that lead to frequent antibiotic treatment making this population more susceptible to acquire pathogens with antibiotic resistance. We aimed to investigate risk factors associated with isolation of multidrug-resistant pathogens in bronchiectasis exacerbations. METHODS: A prospective observational study was conducted in two tertiary-care hospitals, enrolling patients when first exacerbation appeared. Multidrug-resistance was determined according to European Centre of Diseases Prevention and Control classification. RESULTS: Two hundred thirty three exacerbations were included and microorganisms were isolated in 159 episodes. Multidrug-resistant pathogens were found in 20.1% episodes: Pseudomonas aeruginosa (48.5%), methicillin-resistant Staphylococcus aureus (18.2%) and Extended spectrum betalactamase + Enterobacteriaceae (6.1%), and they were more frequent in exacerbations requiring hospitalization (24.5% vs. 10.2%, p: 0.016). Three independent multidrug-resistant risk factors were found: chronic renal disease (Odds ratio (OR), 7.60, 95% CI 1.92–30.09), hospitalization in the previous year (OR, 3.88 95% CI 1.37–11.02) and prior multidrug-resistant isolation (OR, 5.58, 95% CI 2.02–15.46). The proportion of multidrug-resistant in the 233 exacerbations was as follows: 3.9% in patients without risk factors, 12.6% in those with 1 factor and 53.6% if ≥2 risk factors. CONCLUSIONS: Hospitalization in the previous year, chronic renal disease, and prior multidrug-resistant isolation are risk factors for identification multidrug-resistant pathogens in exacerbations. This information may assist clinicians in choosing empirical antibiotics in daily clinical practice.",2017 Sep 30,"['Menéndez, Rosario', 'Méndez, Raúl', 'Polverino, Eva', 'Rosales-Mayor, Edmundo', 'Amara-Elori, Isabel', 'Reyes, Soledad', 'Sahuquillo-Arce, José Miguel', 'Fernández-Barat, Laia', 'Alcaraz, Victoria', 'Torres, Antoni']",BMC Infect Dis,,,True
ef35abb710975a602c24e4eff920d99c022e9132,PMC,"Flavonoid-Rich Extract of Paulownia fortunei Flowers Attenuates Diet-Induced Hyperlipidemia, Hepatic Steatosis and Insulin Resistance in Obesity Mice by AMPK Pathway",http://dx.doi.org/10.3390/nu9090959,PMC5622719,28867797,CC BY,"The flavonoid-rich extract from Paulownia fortunei flowers (EPF) has been reported to prevent obesity and other lipid metabolism disease. However, the mechanism of its protective effects is not yet clear. The objective of this study was to investigate molecular factors involved in the hypoglycemic and hypolipidemic effects of EPF in obese mice fed a high-fat diet (HFD). Male h ICR (Institute of Cancer Research) mice were fed a HFD containing or not containing the EPF (50 or 100 mg/kg) for eight weeks. EPF reduced body weight gain, lipid accumulation in livers and levels of lipid, glucose and insulin in plasma as well as reduced insulin resistance as compared with the HFD group. EPF significantly decreased serum aminotransferase activity of the HFD group. We observed that EPF administration significantly increased the level of AMP-activated kinase (AMPK) phosphorylation and prevented fat deposits in livers and HepG2 cells, but these effects were blocked by compound C (an AMPK inhibitor). The protective effects of EPF were probably associated with the decrease in HMGCR, SREBP-1c and FAS expressions and the increase in CPT1 and phosphor-IRS-1 expressions. Our results suggest that EPF might be a potential natural candidate for the treatment and/or prevention of overweight and hepatic and metabolic-related alterations induced by HFD.",2017 Aug 30,"['Liu, Chanmin', 'Ma, Jieqiong', 'Sun, Jianmei', 'Cheng, Chao', 'Feng, Zhaojun', 'Jiang, Hong', 'Yang, Wei']",Nutrients,,,True
6b1684f4f6c7966725627602b6771c2f1224df89,PMC,"Trend analysis of mortality rates and causes of death in children under 5 years old in Beijing, China from 1992 to 2015 and forecast of mortality into the future: an entire population-based epidemiological study",http://dx.doi.org/10.1136/bmjopen-2017-015941,PMC5623503,28928178,CC BY,"OBJECTIVES: To analyse trends in mortality and causes of death among children aged under 5 years in Beijing, China between 1992 and 2015 and to forecast under-5 mortality rates (U5MRs) for the period 2016–2020. METHODS: An entire population-based epidemiological study was conducted. Data collection was based on the Child Death Reporting Card of the Beijing Under-5 Mortality Rate Surveillance Network. Trends in mortality and leading causes of death were analysed using the χ(2) test and SPSS 19.0 software. An autoregressive integrated moving average (ARIMA) model was fitted to forecast U5MRs between 2016 and 2020 using the EViews 8.0 software. RESULTS: Mortality in neonates, infants and children aged under 5 years decreased by 84.06%, 80.04% and 80.17% from 1992 to 2015, respectively. However, the U5MR increased by 7.20% from 2013 to 2015. Birth asphyxia, congenital heart disease, preterm/low birth weight and other congenital abnormalities comprised the top five causes of death. The greatest, most rapid reduction was that of pneumonia by 92.26%, with an annual average rate of reduction of 10.53%. The distribution of causes of death differed among children of different ages. Accidental asphyxia and sepsis were among the top five causes of death in children aged 28 days to 1 year and accident was among the top five causes in children aged 1–4 years. The U5MRs in Beijing are projected to be 2.88‰, 2.87‰, 2.90‰, 2.97‰ and 3.09‰ for the period 2016–2020, based on the predictive model. CONCLUSION: Beijing has made considerable progress in reducing U5MRs from 1992 to 2015. However, U5MRs could show a slight upward trend from 2016 to 2020. Future considerations for child healthcare include the management of birth asphyxia, congenital heart disease, preterm/low birth weight and other congenital abnormalities. Specific preventative measures should be implemented for children of various age groups.",2017 Sep 18,"['Cao, Han', 'Wang, Jing', 'Li, Yichen', 'Li, Dongyang', 'Guo, Jin', 'Hu, Yifei', 'Meng, Kai', 'He, Dian', 'Liu, Bin', 'Liu, Zheng', 'Qi, Han', 'Zhang, Ling']",BMJ Open,,,True
53c794c9dd0ae2b845a8be57742e1b74fa0f86d6,PMC,"Trend analysis of mortality rates and causes of death in children under 5 years old in Beijing, China from 1992 to 2015 and forecast of mortality into the future: an entire population-based epidemiological study",http://dx.doi.org/10.1136/bmjopen-2017-015941,PMC5623503,28928178,CC BY,"OBJECTIVES: To analyse trends in mortality and causes of death among children aged under 5 years in Beijing, China between 1992 and 2015 and to forecast under-5 mortality rates (U5MRs) for the period 2016–2020. METHODS: An entire population-based epidemiological study was conducted. Data collection was based on the Child Death Reporting Card of the Beijing Under-5 Mortality Rate Surveillance Network. Trends in mortality and leading causes of death were analysed using the χ(2) test and SPSS 19.0 software. An autoregressive integrated moving average (ARIMA) model was fitted to forecast U5MRs between 2016 and 2020 using the EViews 8.0 software. RESULTS: Mortality in neonates, infants and children aged under 5 years decreased by 84.06%, 80.04% and 80.17% from 1992 to 2015, respectively. However, the U5MR increased by 7.20% from 2013 to 2015. Birth asphyxia, congenital heart disease, preterm/low birth weight and other congenital abnormalities comprised the top five causes of death. The greatest, most rapid reduction was that of pneumonia by 92.26%, with an annual average rate of reduction of 10.53%. The distribution of causes of death differed among children of different ages. Accidental asphyxia and sepsis were among the top five causes of death in children aged 28 days to 1 year and accident was among the top five causes in children aged 1–4 years. The U5MRs in Beijing are projected to be 2.88‰, 2.87‰, 2.90‰, 2.97‰ and 3.09‰ for the period 2016–2020, based on the predictive model. CONCLUSION: Beijing has made considerable progress in reducing U5MRs from 1992 to 2015. However, U5MRs could show a slight upward trend from 2016 to 2020. Future considerations for child healthcare include the management of birth asphyxia, congenital heart disease, preterm/low birth weight and other congenital abnormalities. Specific preventative measures should be implemented for children of various age groups.",2017 Sep 18,"['Cao, Han', 'Wang, Jing', 'Li, Yichen', 'Li, Dongyang', 'Guo, Jin', 'Hu, Yifei', 'Meng, Kai', 'He, Dian', 'Liu, Bin', 'Liu, Zheng', 'Qi, Han', 'Zhang, Ling']",BMJ Open,,,True
5731445d010b69d663005de6dac188fe26b9c120,PMC,"Trend analysis of mortality rates and causes of death in children under 5 years old in Beijing, China from 1992 to 2015 and forecast of mortality into the future: an entire population-based epidemiological study",http://dx.doi.org/10.1136/bmjopen-2017-015941,PMC5623503,28928178,CC BY,"OBJECTIVES: To analyse trends in mortality and causes of death among children aged under 5 years in Beijing, China between 1992 and 2015 and to forecast under-5 mortality rates (U5MRs) for the period 2016–2020. METHODS: An entire population-based epidemiological study was conducted. Data collection was based on the Child Death Reporting Card of the Beijing Under-5 Mortality Rate Surveillance Network. Trends in mortality and leading causes of death were analysed using the χ(2) test and SPSS 19.0 software. An autoregressive integrated moving average (ARIMA) model was fitted to forecast U5MRs between 2016 and 2020 using the EViews 8.0 software. RESULTS: Mortality in neonates, infants and children aged under 5 years decreased by 84.06%, 80.04% and 80.17% from 1992 to 2015, respectively. However, the U5MR increased by 7.20% from 2013 to 2015. Birth asphyxia, congenital heart disease, preterm/low birth weight and other congenital abnormalities comprised the top five causes of death. The greatest, most rapid reduction was that of pneumonia by 92.26%, with an annual average rate of reduction of 10.53%. The distribution of causes of death differed among children of different ages. Accidental asphyxia and sepsis were among the top five causes of death in children aged 28 days to 1 year and accident was among the top five causes in children aged 1–4 years. The U5MRs in Beijing are projected to be 2.88‰, 2.87‰, 2.90‰, 2.97‰ and 3.09‰ for the period 2016–2020, based on the predictive model. CONCLUSION: Beijing has made considerable progress in reducing U5MRs from 1992 to 2015. However, U5MRs could show a slight upward trend from 2016 to 2020. Future considerations for child healthcare include the management of birth asphyxia, congenital heart disease, preterm/low birth weight and other congenital abnormalities. Specific preventative measures should be implemented for children of various age groups.",2017 Sep 18,"['Cao, Han', 'Wang, Jing', 'Li, Yichen', 'Li, Dongyang', 'Guo, Jin', 'Hu, Yifei', 'Meng, Kai', 'He, Dian', 'Liu, Bin', 'Liu, Zheng', 'Qi, Han', 'Zhang, Ling']",BMJ Open,,,True
3855de3900dee3cecb63982884763c5dac76b8cb,PMC,Intracellular Crosslinking of Filoviral Nucleoproteins with Xintrabodies Restricts Viral Packaging,http://dx.doi.org/10.3389/fimmu.2017.01197,PMC5623874,29021793,CC BY,"Viruses assemble large macromolecular repeat structures that become part of the infectious particles or virions. Ribonucleocapsids (RNCs) of negative strand RNA viruses are a prime example where repetition of nucleoprotein (NP) along the genome creates a core polymeric helical scaffold that accommodates other nucleocapsid proteins including viral polymerase. The RNCs are transported through the cytosol for packaging into virions through association with viral matrix proteins at cell membranes. We hypothesized that RNC would be ideal targets for crosslinkers engineered to promote aberrant protein–protein interactions, thereby blocking their orderly transport and packaging. Previously, we had generated single-domain antibodies (sdAbs) against Filoviruses that have all targeted highly conserved C-terminal regions of NP known to be repetitively exposed along the length of the RNCs of Marburgvirus (MARV) and Ebolavirus (EBOV). Our crosslinker design consisted of dimeric sdAb expressed intracellularly, which we call Xintrabodies (X- for crosslinking). Electron microscopy of purified NP polymers incubated with purified sdAb constructs showed NP aggregation occurred in a genus-specific manner with dimeric and not monomeric sdAb. A virus-like particle (VLP) assay was used for initial evaluation where we found that dimeric sdAb inhibited NP incorporation into VP40-based VLPs whereas monomeric sdAb did not. Inhibition of NP packaging was genus specific. Confocal microscopy revealed dimeric sdAb was diffuse when expressed alone but focused on pools of NP when the two were coexpressed, while monomeric sdAb showed ambivalent partition. Infection of stable Vero cell lines expressing dimeric sdAb specific for either MARV or EBOV NP resulted in smaller plaques and reduced progeny of cognate virus relative to wild-type Vero cells. Though the impact was marginal at later time-points, the collective data suggest that viral replication can be reduced by crosslinking intracellular NP using relatively small amounts of dimeric sdAb to restrict NP packaging. The stoichiometry and ease of application of the approach would likely benefit from transitioning away from intracellular expression of crosslinking sdAb to exogenous delivery of antibody. By retuning sdAb specificity, the approach of crosslinking highly conserved regions of assembly critical proteins may well be applicable to inhibiting replication processes of a broad spectrum of viruses.",2017 Sep 27,"['Darling, Tamarand Lee', 'Sherwood, Laura Jo', 'Hayhurst, Andrew']",Front Immunol,,,True
23ac830cd2c26493bcfc9aa4877a5aab07f26680,PMC,Intracellular Crosslinking of Filoviral Nucleoproteins with Xintrabodies Restricts Viral Packaging,http://dx.doi.org/10.3389/fimmu.2017.01197,PMC5623874,29021793,CC BY,"Viruses assemble large macromolecular repeat structures that become part of the infectious particles or virions. Ribonucleocapsids (RNCs) of negative strand RNA viruses are a prime example where repetition of nucleoprotein (NP) along the genome creates a core polymeric helical scaffold that accommodates other nucleocapsid proteins including viral polymerase. The RNCs are transported through the cytosol for packaging into virions through association with viral matrix proteins at cell membranes. We hypothesized that RNC would be ideal targets for crosslinkers engineered to promote aberrant protein–protein interactions, thereby blocking their orderly transport and packaging. Previously, we had generated single-domain antibodies (sdAbs) against Filoviruses that have all targeted highly conserved C-terminal regions of NP known to be repetitively exposed along the length of the RNCs of Marburgvirus (MARV) and Ebolavirus (EBOV). Our crosslinker design consisted of dimeric sdAb expressed intracellularly, which we call Xintrabodies (X- for crosslinking). Electron microscopy of purified NP polymers incubated with purified sdAb constructs showed NP aggregation occurred in a genus-specific manner with dimeric and not monomeric sdAb. A virus-like particle (VLP) assay was used for initial evaluation where we found that dimeric sdAb inhibited NP incorporation into VP40-based VLPs whereas monomeric sdAb did not. Inhibition of NP packaging was genus specific. Confocal microscopy revealed dimeric sdAb was diffuse when expressed alone but focused on pools of NP when the two were coexpressed, while monomeric sdAb showed ambivalent partition. Infection of stable Vero cell lines expressing dimeric sdAb specific for either MARV or EBOV NP resulted in smaller plaques and reduced progeny of cognate virus relative to wild-type Vero cells. Though the impact was marginal at later time-points, the collective data suggest that viral replication can be reduced by crosslinking intracellular NP using relatively small amounts of dimeric sdAb to restrict NP packaging. The stoichiometry and ease of application of the approach would likely benefit from transitioning away from intracellular expression of crosslinking sdAb to exogenous delivery of antibody. By retuning sdAb specificity, the approach of crosslinking highly conserved regions of assembly critical proteins may well be applicable to inhibiting replication processes of a broad spectrum of viruses.",2017 Sep 27,"['Darling, Tamarand Lee', 'Sherwood, Laura Jo', 'Hayhurst, Andrew']",Front Immunol,,,False
4ebfebb9ccfdcdd2b4bacde19e1098620788808d,PMC,Identification of isoliquiritigenin as an activator that stimulates the enzymatic production of glycyrrhetinic acid monoglucuronide,http://dx.doi.org/10.1038/s41598-017-10154-y,PMC5624897,28970510,CC BY,"Glycyrrhetinic acid monoglucuronide (GAMG) is a great value-added and has considerable commercial interest due to its strong pharmacological activities and functional low-calorie sweetener. However GAMG is quite rare in natural plants, and it must be prepared from glycyrrhizin (GL) by hydrolysing one terminal glucuronic acid. β-Glucuronidase is the key enzyme in the biotransformation of GL to GAMG, but its activities need to be enhanced to facilitate the industrial large-scale production of GAMG. In this study, we identified that isoliquiritigenin (ISL), as one of chemical compositions from the total flavonoids glycyrrhiza (TFG), can significantly enhance β-glucuronidase activity in vitro. Measurements using high-performance liquid chromatography (HPLC) showed that the activity of β-glucuronidase could be increased by 2.66-fold via the addition of ISL to a β-glucuronidase solution that contained GL at a 3:10 molar ratio of ISL to GL. ISL was concluded to be an activator because ISL could reduce the K(m) and E(a) of β-glucuronidase reacting with GL. This study sheds new light on the mechanism of β-glucuronidase and helps to make industrial production of GAMG through fermentation feasible.",2017 Oct 2,"['Wang, Xiaoxue', 'Wang, Dong', 'Huo, Yixin', 'Dai, Dazhang', 'Li, Chihua', 'Li, Chun', 'Liu, Guiyan']",Sci Rep,,,False
732933f36dc0c57fd8094f545c5e82d7192a13c7,PMC,Identification of isoliquiritigenin as an activator that stimulates the enzymatic production of glycyrrhetinic acid monoglucuronide,http://dx.doi.org/10.1038/s41598-017-10154-y,PMC5624897,28970510,CC BY,"Glycyrrhetinic acid monoglucuronide (GAMG) is a great value-added and has considerable commercial interest due to its strong pharmacological activities and functional low-calorie sweetener. However GAMG is quite rare in natural plants, and it must be prepared from glycyrrhizin (GL) by hydrolysing one terminal glucuronic acid. β-Glucuronidase is the key enzyme in the biotransformation of GL to GAMG, but its activities need to be enhanced to facilitate the industrial large-scale production of GAMG. In this study, we identified that isoliquiritigenin (ISL), as one of chemical compositions from the total flavonoids glycyrrhiza (TFG), can significantly enhance β-glucuronidase activity in vitro. Measurements using high-performance liquid chromatography (HPLC) showed that the activity of β-glucuronidase could be increased by 2.66-fold via the addition of ISL to a β-glucuronidase solution that contained GL at a 3:10 molar ratio of ISL to GL. ISL was concluded to be an activator because ISL could reduce the K(m) and E(a) of β-glucuronidase reacting with GL. This study sheds new light on the mechanism of β-glucuronidase and helps to make industrial production of GAMG through fermentation feasible.",2017 Oct 2,"['Wang, Xiaoxue', 'Wang, Dong', 'Huo, Yixin', 'Dai, Dazhang', 'Li, Chihua', 'Li, Chun', 'Liu, Guiyan']",Sci Rep,,,True
ed8fa7a5f18148527c4280df39446a4102bd5949,PMC,Commentary: Outbreak of Chikungunya in Pakistan,http://dx.doi.org/10.3389/fpubh.2017.00261,PMC5625004,29034228,CC BY,,2017 Sep 28,"['Mallhi, Tauqeer Hussain', 'Khan, Yusra Habib', 'Khan, Amer Hayat', 'Tanveer, Nida', 'Khan, Omaid Hayat', 'Aftab, Raja Ahsan']",Front Public Health,,,True
4ada63940f8817b1305316a9c44cfbb5bc39b762,PMC,Disease reservoirs: from conceptual frameworks to applicable criteria,http://dx.doi.org/10.1038/emi.2017.65,PMC5625316,28874791,CC BY,"Central to the One Health approach and any disease eradication program is the question of whether a pathogen has a non-human reservoir. Despite well-established conceptual frameworks that define a reservoir of infection, empirical characterization of reservoirs often remains controversial, challenging and sometimes misleading. What is essentially missing are applicable requirements that standardize the use of the term ‘reservoir of infection’ across multiple disciplines. We propose an empirical framework, considering maintenance and feasible transmission of a pathogen, to standardize the acceptance of a disease reservoir across multiple disciplines. We demonstrate the intended use of these requirements by applying them to different diseases that are known to infect both humans and animals.",2017 Sep 6,"['Hallmaier-Wacker, Luisa K', 'Munster, Vincent J', 'Knauf, Sascha']",Emerg Microbes Infect,,,True
c6cd179dd8309719306a785c5d1333d6a9cafaf0,PMC,To announce or not to announce: What is known about the 2016–2017 influenza season in Hong Kong?,http://dx.doi.org/10.1038/emi.2017.76,PMC5625322,,CC BY,,2017 Sep 6,"['Cheung, Pak-Hin Hinson', 'Chan, Chi-Ping', 'Jin, Dong-Yan']",Emerg Microbes Infect,,,False
f889617cc2152ead5c5070ee3ee24dcf86248bad,PMC,Cholesterol and host cell surface proteins contribute to cell-cell fusion induced by the Burkholderia type VI secretion system 5,http://dx.doi.org/10.1371/journal.pone.0185715,PMC5626464,28973030,CC BY,"Following escape into the cytoplasm of host cells, Burkholderia pseudomallei and the related species Burkholderia thailandensis employ the type VI secretion system 5 (T6SS-5) to induce plasma membrane fusion with an adjacent host cell. This process leads to the formation of multinucleated giant cells and facilitates bacterial access to an uninfected host cell in a direct manner. Despite its importance in virulence, the mechanism of the T6SS-5 and the role of host cell factors in cell-cell fusion remain elusive. To date, the T6SS-5 is the only system of bacterial origin known to induce host-cell fusion. To gain insight into the nature of T6SS-5-stimulated membrane fusion, we investigated the contribution of cholesterol and proteins exposed on the host cell surface, which were shown to be critically involved in virus-mediated giant cell formation. In particular, we analyzed the effect of host cell surface protein and cholesterol depletion on the formation of multinucleated giant cells induced by B. thailandensis. Acute protease treatment of RAW264.7 macrophages during infection with B. thailandensis followed by agarose overlay assays revealed a strong reduction in the number of cell-cell fusions compared with EDTA treated cells. Similarly, proteolytic treatment of specifically infected donor cells or uninfected recipient cells significantly decreased multinucleated giant cell formation. Furthermore, modulating host cell cholesterol content by acute cholesterol depletion from cellular membranes by methyl- β-cyclodextrin treatment or exogenous addition of cholesterol impaired the ability of B. thailandensis to induce cell-cell fusions. The requirement of physiological cholesterol levels suggests that the membrane organization or mechanical properties of the lipid bilayer influence the fusion process. Altogether, our data suggest that membrane fusion induced by B. pseudomallei and B. thailandensis involves a complex interplay between the T6SS-5 and the host cell.",2017 Oct 3,"['Whiteley, Liam', 'Haug, Maria', 'Klein, Kristina', 'Willmann, Matthias', 'Bohn, Erwin', 'Chiantia, Salvatore', 'Schwarz, Sandra']",PLoS One,,,True
a63e670d74fe754980355a4f59c770955914745d,PMC,Interferon-λs: Front-Line Guardians of Immunity and Homeostasis in the Respiratory Tract,http://dx.doi.org/10.3389/fimmu.2017.01232,PMC5626824,29033947,CC BY,"Type III interferons (IFNs), also termed lambda IFNs (IFNλs) or interleukins-28/29, constitute a new addition to the IFN family. They are induced upon infection and are particularly abundant at barrier surfaces, such as the respiratory and gastrointestinal tracts. Although they signal through a unique heterodimeric receptor complex comprising IFNLR1 and IL10RB, they activate a downstream signaling pathway remarkably similar to that of type I IFNs and share many functions with them. Yet, they also have important differences which are only now starting to unfold. Here, we review the current literature implicating type III IFNs in the regulation of immunity and homeostasis in the respiratory tract. We survey the common and unique characteristics of type III IFNs in terms of expression patterns, cellular targets, and biological activities and discuss their emerging role in first line defenses against respiratory viral infections. We further explore their immune modulatory functions and their involvement in the regulation of inflammatory responses during chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Type III IFNs are, therefore, arising as front-line guardians of immune defenses in the respiratory tract, fine tuning inflammation, and as potential novel therapeutics for the treatment of diverse respiratory diseases, including influenza virus infection and asthma.",2017 Sep 29,"['Andreakos, Evangelos', 'Salagianni, Maria', 'Galani, Ioanna E.', 'Koltsida, Ourania']",Front Immunol,,,True
0b48e310b1f5d0205ad5ffa292d950d2808185c0,PMC,Microarray Analysis Identifies the Potential Role of Long Non-Coding RNA in Regulating Neuroinflammation during Japanese Encephalitis Virus Infection,http://dx.doi.org/10.3389/fimmu.2017.01237,PMC5626832,29033949,CC BY,"Japanese encephalitis virus (JEV) is the leading cause of epidemic encephalitis worldwide. JEV-induced neuroinflammation is characterized by profound neuronal cells damage accompanied by activation of glial cells. Albeit long non-coding RNAs (lncRNAs) have been emerged as important regulatory RNAs with profound effects on various biological processes, it is unknown how lncRNAs regulate JEV-induced inflammation. Here, using microarray approach, we identified 618 lncRNAs and 1,007 mRNAs differentially expressed in JEV-infected mice brain. The functional annotation analysis revealed that differentially regulated transcripts were predominantly involved in various signaling pathways related to host immune and inflammatory responses. The lncRNAs with their potential to regulate JEV-induced inflammatory response were identified by constructing the lncRNA-mRNA coexpression network. Furthermore, silencing of the two selected lncRNAs (E52329 and N54010) resulted in reducing the phosphorylation of JNK and MKK4, which are known to be involved during inflammatory response. Collectively, we first demonstrated the transcriptomic landscape of lncRNAs in mice brain infected with JEV and analyzed the coexpression network of differentially regulated lncRNAs and mRNAs during JEV infection. Our results provide a better understanding of the host response to JEV infection and suggest that the identified lncRNAs may be used as potential therapeutic targets for the management of Japanese encephalitis.",2017 Sep 29,"['Li, Yunchuan', 'Zhang, Hao', 'Zhu, Bibo', 'Ashraf, Usama', 'Chen, Zheng', 'Xu, Qiuping', 'Zhou, Dengyuan', 'Zheng, Bohan', 'Song, Yunfeng', 'Chen, Huanchun', 'Ye, Jing', 'Cao, Shengbo']",Front Immunol,,,True
c682f8e05b7363e2407b3055826f6c93b6c1f3ad,PMC,Influenzanet: Citizens Among 10 Countries Collaborating to Monitor Influenza in Europe,http://dx.doi.org/10.2196/publichealth.7429,PMC5627046,28928112,CC BY,"BACKGROUND: The wide availability of the Internet and the growth of digital communication technologies have become an important tool for epidemiological studies and health surveillance. Influenzanet is a participatory surveillance system monitoring the incidence of influenza-like illness (ILI) in Europe since 2003. It is based on data provided by volunteers who self-report their symptoms via the Internet throughout the influenza season and currently involves 10 countries. OBJECTIVE: In this paper, we describe the Influenzanet system and provide an overview of results from several analyses that have been performed with the collected data, which include participant representativeness analyses, data validation (comparing ILI incidence rates between Influenzanet and sentinel medical practice networks), identification of ILI risk factors, and influenza vaccine effectiveness (VE) studies previously published. Additionally, we present new VE analyses for the Netherlands, stratified by age and chronic illness and offer suggestions for further work and considerations on the continuity and sustainability of the participatory system. METHODS: Influenzanet comprises country-specific websites where residents can register to become volunteers to support influenza surveillance and have access to influenza-related information. Participants are recruited through different communication channels. Following registration, volunteers submit an intake questionnaire with their postal code and sociodemographic and medical characteristics, after which they are invited to report their symptoms via a weekly electronic newsletter reminder. Several thousands of participants have been engaged yearly in Influenzanet, with over 36,000 volunteers in the 2015-16 season alone. RESULTS: In summary, for some traits and in some countries (eg, influenza vaccination rates in the Netherlands), Influenzanet participants were representative of the general population. However, for other traits, they were not (eg, participants underrepresent the youngest and oldest age groups in 7 countries). The incidence of ILI in Influenzanet was found to be closely correlated although quantitatively higher than that obtained by the sentinel medical practice networks. Various risk factors for acquiring an ILI infection were identified. The VE studies performed with Influenzanet data suggest that this surveillance system could develop into a complementary tool to measure the effectiveness of the influenza vaccine, eventually in real time. CONCLUSIONS: Results from these analyses illustrate that Influenzanet has developed into a fast and flexible monitoring system that can complement the traditional influenza surveillance performed by sentinel medical practices. The uniformity of Influenzanet allows for direct comparison of ILI rates between countries. It also has the important advantage of yielding individual data, which can be used to identify risk factors. The way in which the Influenzanet system is constructed allows the collection of data that could be extended beyond those of ILI cases to monitor pandemic influenza and other common or emerging diseases.",2017 Sep 19,"['Koppeschaar, Carl E', 'Colizza, Vittoria', 'Guerrisi, Caroline', 'Turbelin, Clément', 'Duggan, Jim', 'Edmunds, W John', 'Kjelsø, Charlotte', 'Mexia, Ricardo', 'Moreno, Yamir', 'Meloni, Sandro', 'Paolotti, Daniela', 'Perrotta, Daniela', 'van Straten, Edward', 'Franco, Ana O']",JMIR Public Health Surveill,,,True
f2ce9e73f368fc128cd28a0246b3ff8aa3079a42,PMC,Influenzanet: Citizens Among 10 Countries Collaborating to Monitor Influenza in Europe,http://dx.doi.org/10.2196/publichealth.7429,PMC5627046,28928112,CC BY,"BACKGROUND: The wide availability of the Internet and the growth of digital communication technologies have become an important tool for epidemiological studies and health surveillance. Influenzanet is a participatory surveillance system monitoring the incidence of influenza-like illness (ILI) in Europe since 2003. It is based on data provided by volunteers who self-report their symptoms via the Internet throughout the influenza season and currently involves 10 countries. OBJECTIVE: In this paper, we describe the Influenzanet system and provide an overview of results from several analyses that have been performed with the collected data, which include participant representativeness analyses, data validation (comparing ILI incidence rates between Influenzanet and sentinel medical practice networks), identification of ILI risk factors, and influenza vaccine effectiveness (VE) studies previously published. Additionally, we present new VE analyses for the Netherlands, stratified by age and chronic illness and offer suggestions for further work and considerations on the continuity and sustainability of the participatory system. METHODS: Influenzanet comprises country-specific websites where residents can register to become volunteers to support influenza surveillance and have access to influenza-related information. Participants are recruited through different communication channels. Following registration, volunteers submit an intake questionnaire with their postal code and sociodemographic and medical characteristics, after which they are invited to report their symptoms via a weekly electronic newsletter reminder. Several thousands of participants have been engaged yearly in Influenzanet, with over 36,000 volunteers in the 2015-16 season alone. RESULTS: In summary, for some traits and in some countries (eg, influenza vaccination rates in the Netherlands), Influenzanet participants were representative of the general population. However, for other traits, they were not (eg, participants underrepresent the youngest and oldest age groups in 7 countries). The incidence of ILI in Influenzanet was found to be closely correlated although quantitatively higher than that obtained by the sentinel medical practice networks. Various risk factors for acquiring an ILI infection were identified. The VE studies performed with Influenzanet data suggest that this surveillance system could develop into a complementary tool to measure the effectiveness of the influenza vaccine, eventually in real time. CONCLUSIONS: Results from these analyses illustrate that Influenzanet has developed into a fast and flexible monitoring system that can complement the traditional influenza surveillance performed by sentinel medical practices. The uniformity of Influenzanet allows for direct comparison of ILI rates between countries. It also has the important advantage of yielding individual data, which can be used to identify risk factors. The way in which the Influenzanet system is constructed allows the collection of data that could be extended beyond those of ILI cases to monitor pandemic influenza and other common or emerging diseases.",2017 Sep 19,"['Koppeschaar, Carl E', 'Colizza, Vittoria', 'Guerrisi, Caroline', 'Turbelin, Clément', 'Duggan, Jim', 'Edmunds, W John', 'Kjelsø, Charlotte', 'Mexia, Ricardo', 'Moreno, Yamir', 'Meloni, Sandro', 'Paolotti, Daniela', 'Perrotta, Daniela', 'van Straten, Edward', 'Franco, Ana O']",JMIR Public Health Surveill,,,True
7d59b9187e7e96661594c50c8a8c9eab6b1ba177,PMC,An avian influenza H7 DNA priming vaccine is safe and immunogenic in a randomized phase I clinical trial,http://dx.doi.org/10.1038/s41541-017-0016-6,PMC5627236,29263871,CC BY,"A novel avian influenza subtype, A/H7N9, emerged in 2013 and represents a public health threat with pandemic potential. We have previously shown that DNA vaccine priming increases the magnitude and quality of antibody responses to H5N1 monovalent inactivated boost. We now report the safety and immunogenicity of a H7 DNA-H7N9 monovalent inactivated vaccine prime-boost regimen. In this Phase 1, open label, randomized clinical trial, we evaluated three H7N9 vaccination regimens in healthy adults, with a prime-boost interval of 16 weeks. Group 1 received H7 DNA vaccine prime and H7N9 monovalent inactivated vaccine boost. Group 2 received H7 DNA and H7N9 monovalent inactivated vaccine as a prime and H7N9 monovalent inactivated vaccine as a boost. Group 3 received H7N9 monovalent inactivated vaccine in a homologous prime-boost regimen. Overall, 30 individuals between 20 to 60 years old enrolled and 28 completed both vaccinations. All injections were well tolerated with no serious adverse events. 2 weeks post-boost, 50% of Group 1 and 33% of Group 2 achieved a HAI titer ≥1:40 compared with 11% of Group 3. Also, at least a fourfold increase in neutralizing antibody responses was seen in 90% of Group 1, 100% of Group 2, and 78% of Group 3 subjects. Peak neutralizing antibody geometric mean titers were significantly greater for Group 1 (GMT = 440.61, p < 0.05) and Group 2 (GMT = 331, p = 0.02) when compared with Group 3 (GMT = 86.11). A novel H7 DNA vaccine was safe, well-tolerated, and immunogenic when boosted with H7N9 monovalent inactivated vaccine, while priming for higher HAI and neutralizing antibody titers than H7N9 monovalent inactivated vaccine alone.",2017 Jun 1,"['DeZure, Adam D.', 'Coates, Emily E.', 'Hu, Zonghui', 'Yamshchikov, Galina V.', 'Zephir, Kathryn L.', 'Enama, Mary E.', 'Plummer, Sarah H.', 'Gordon, Ingelise J.', 'Kaltovich, Florence', 'Andrews, Sarah', 'McDermott, Adrian', 'Crank, Michelle C.', 'Koup, Richard A', 'Schwartz, Richard M.', 'Bailer, Robert T.', 'Sun, Xiangjie', 'Mascola, John R.', 'Tumpey, Terrence M.', 'Graham, Barney S.', 'Ledgerwood, Julie E.']",NPJ Vaccines,,,True
59b6229ca07d737a197ae0708282a1f6ed4fa435,PMC,An avian influenza H7 DNA priming vaccine is safe and immunogenic in a randomized phase I clinical trial,http://dx.doi.org/10.1038/s41541-017-0016-6,PMC5627236,29263871,CC BY,"A novel avian influenza subtype, A/H7N9, emerged in 2013 and represents a public health threat with pandemic potential. We have previously shown that DNA vaccine priming increases the magnitude and quality of antibody responses to H5N1 monovalent inactivated boost. We now report the safety and immunogenicity of a H7 DNA-H7N9 monovalent inactivated vaccine prime-boost regimen. In this Phase 1, open label, randomized clinical trial, we evaluated three H7N9 vaccination regimens in healthy adults, with a prime-boost interval of 16 weeks. Group 1 received H7 DNA vaccine prime and H7N9 monovalent inactivated vaccine boost. Group 2 received H7 DNA and H7N9 monovalent inactivated vaccine as a prime and H7N9 monovalent inactivated vaccine as a boost. Group 3 received H7N9 monovalent inactivated vaccine in a homologous prime-boost regimen. Overall, 30 individuals between 20 to 60 years old enrolled and 28 completed both vaccinations. All injections were well tolerated with no serious adverse events. 2 weeks post-boost, 50% of Group 1 and 33% of Group 2 achieved a HAI titer ≥1:40 compared with 11% of Group 3. Also, at least a fourfold increase in neutralizing antibody responses was seen in 90% of Group 1, 100% of Group 2, and 78% of Group 3 subjects. Peak neutralizing antibody geometric mean titers were significantly greater for Group 1 (GMT = 440.61, p < 0.05) and Group 2 (GMT = 331, p = 0.02) when compared with Group 3 (GMT = 86.11). A novel H7 DNA vaccine was safe, well-tolerated, and immunogenic when boosted with H7N9 monovalent inactivated vaccine, while priming for higher HAI and neutralizing antibody titers than H7N9 monovalent inactivated vaccine alone.",2017 Jun 1,"['DeZure, Adam D.', 'Coates, Emily E.', 'Hu, Zonghui', 'Yamshchikov, Galina V.', 'Zephir, Kathryn L.', 'Enama, Mary E.', 'Plummer, Sarah H.', 'Gordon, Ingelise J.', 'Kaltovich, Florence', 'Andrews, Sarah', 'McDermott, Adrian', 'Crank, Michelle C.', 'Koup, Richard A', 'Schwartz, Richard M.', 'Bailer, Robert T.', 'Sun, Xiangjie', 'Mascola, John R.', 'Tumpey, Terrence M.', 'Graham, Barney S.', 'Ledgerwood, Julie E.']",NPJ Vaccines,,,True
d4798a48149f9f99e2140e596a4246b15d05fd50,PMC,Antibody therapies for the prevention and treatment of viral infections,http://dx.doi.org/10.1038/s41541-017-0019-3,PMC5627241,29263875,CC BY,"Antibodies are an important component in host immune responses to viral pathogens. Because of their unique maturation process, antibodies can evolve to be highly specific to viral antigens. Physicians and researchers have been relying on such high specificity in their quest to understand host–viral interaction and viral pathogenesis mechanisms and to find potential cures for viral infection and disease. With more than 60 recombinant monoclonal antibodies developed for human use in the last 20 years, monoclonal antibodies are now considered a viable therapeutic modality for infectious disease targets, including newly emerging viral pathogens such as Ebola representing heightened public health concerns, as well as pathogens that have long been known, such as human cytomegalovirus. Here, we summarize some recent advances in identification and characterization of monoclonal antibodies suitable as drug candidates for clinical evaluation, and review some promising candidates in the development pipeline.",2017 Jul 10,"['Salazar, Georgina', 'Zhang, Ningyan', 'Fu, Tong-Ming', 'An, Zhiqiang']",NPJ Vaccines,,,True
003a81cfaf6b18d88809ab832db59afc3dc9e82e,PMC,DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections,http://dx.doi.org/10.1038/s41541-017-0020-x,PMC5627301,29263874,CC BY,"Influenza virus remains a significant public health threat despite innovative vaccines and antiviral drugs. A major limitation to current vaccinations and therapies against influenza virus is pathogenic diversity generated by shift and drift. A simple, cost-effective passive immunization strategy via in vivo production of cross-protective antibody molecules may augment existing vaccines and antiviral drugs in seasonal and pandemic outbreaks. We engineered synthetic plasmid DNA to encode two novel and broadly cross-protective monoclonal antibodies targeting influenza A and B. We utilized enhanced in vivo delivery of these plasmid DNA-encoded monoclonal antibody (DMAb) constructs and show that this strategy induces robust levels of functional antibodies directed against influenza A and B viruses in mouse sera. Mice receiving a single inoculation with anti-influenza A DMAb survive lethal Group 1 H1 and Group 2 H3 influenza A challenges, while inoculation with anti-influenza B DMAb yields protection against lethal Victoria and Yamagata lineage influenza B morbidity and mortality. Furthermore, these two DMAbs can be delivered coordinately resulting in exceptionally broad protection against both influenza A and B. We demonstrate this protection is similar to that achieved by conventional protein antibody delivery. DMAbs warrant further investigation as a novel immune therapy platform with distinct advantages for sustained immunoprophylaxis against influenza.",2017 Jul 6,"['Elliott, Sarah T. C.', 'Kallewaard, Nicole L.', 'Benjamin, Ebony', 'Wachter-Rosati, Leslie', 'McAuliffe, Josephine M.', 'Patel, Ami', 'Smith, Trevor R. F.', 'Schultheis, Katherine', 'Park, Daniel H.', 'Flingai, Seleeke', 'Wise, Megan C.', 'Mendoza, Janess', 'Ramos, Stephanie', 'Broderick, Kate E.', 'Yan, Jian', 'Humeau, Laurent M.', 'Sardesai, Niranjan Y.', 'Muthumani, Kar', 'Zhu, Qing', 'Weiner, David B.']",NPJ Vaccines,,,False
b1734efe5e012f983218c7155fc434cada1a35ec,PMC,DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections,http://dx.doi.org/10.1038/s41541-017-0020-x,PMC5627301,29263874,CC BY,"Influenza virus remains a significant public health threat despite innovative vaccines and antiviral drugs. A major limitation to current vaccinations and therapies against influenza virus is pathogenic diversity generated by shift and drift. A simple, cost-effective passive immunization strategy via in vivo production of cross-protective antibody molecules may augment existing vaccines and antiviral drugs in seasonal and pandemic outbreaks. We engineered synthetic plasmid DNA to encode two novel and broadly cross-protective monoclonal antibodies targeting influenza A and B. We utilized enhanced in vivo delivery of these plasmid DNA-encoded monoclonal antibody (DMAb) constructs and show that this strategy induces robust levels of functional antibodies directed against influenza A and B viruses in mouse sera. Mice receiving a single inoculation with anti-influenza A DMAb survive lethal Group 1 H1 and Group 2 H3 influenza A challenges, while inoculation with anti-influenza B DMAb yields protection against lethal Victoria and Yamagata lineage influenza B morbidity and mortality. Furthermore, these two DMAbs can be delivered coordinately resulting in exceptionally broad protection against both influenza A and B. We demonstrate this protection is similar to that achieved by conventional protein antibody delivery. DMAbs warrant further investigation as a novel immune therapy platform with distinct advantages for sustained immunoprophylaxis against influenza.",2017 Jul 6,"['Elliott, Sarah T. C.', 'Kallewaard, Nicole L.', 'Benjamin, Ebony', 'Wachter-Rosati, Leslie', 'McAuliffe, Josephine M.', 'Patel, Ami', 'Smith, Trevor R. F.', 'Schultheis, Katherine', 'Park, Daniel H.', 'Flingai, Seleeke', 'Wise, Megan C.', 'Mendoza, Janess', 'Ramos, Stephanie', 'Broderick, Kate E.', 'Yan, Jian', 'Humeau, Laurent M.', 'Sardesai, Niranjan Y.', 'Muthumani, Kar', 'Zhu, Qing', 'Weiner, David B.']",NPJ Vaccines,,,True
a02952893a51f2255a8d9d84b3eba6fe1b113996,PMC,Protein nanovaccine confers robust immunity against Toxoplasma,http://dx.doi.org/10.1038/s41541-017-0024-6,PMC5627305,29263879,CC BY,"We designed and produced a self-assembling protein nanoparticle. This self-assembling protein nanoparticle contains five CD8(+) HLA-A03-11 supertypes-restricted epitopes from antigens expressed during Toxoplasma gondii’s lifecycle, the universal CD4(+) T cell epitope PADRE, and flagellin as a scaffold and TLR5 agonist. These CD8(+) T cell epitopes were separated by N/KAAA spacers and optimized for proteasomal cleavage. Self-assembling protein nanoparticle adjuvanted with TLR4 ligand-emulsion GLA-SE were evaluated for their efficacy in inducing IFN-γ responses and protection of HLA-A*1101 transgenic mice against T. gondii. Immunization, using self-assembling protein nanoparticle-GLA-SE, activated CD8(+) T cells to produce IFN-γ. Self-assembling protein nanoparticle-GLA-SE also protected HLA-A*1101 transgenic mice against subsequent challenge with Type II parasites. Hence, combining CD8(+) T cell-eliciting peptides and PADRE into a multi-epitope protein that forms a nanoparticle, administered with GLA-SE, leads to efficient presentation by major histocompatibility complex Class I and II molecules. Furthermore, these results suggest that activation of TLR4 and TLR5 could be useful for development of vaccines that elicit T cells to prevent toxoplasmosis in humans.",2017 Sep 5,"['El Bissati, Kamal', 'Zhou, Ying', 'Paulillo, Sara Maria', 'Raman, Senthil Kumar', 'Karch, Christopher P.', 'Roberts, Craig W.', 'Lanar, David E.', 'Reed, Steve', 'Fox, Chris', 'Carter, Darrick', 'Alexander, Jeff', 'Sette, Alessandro', 'Sidney, John', 'Lorenzi, Hernan', 'Begeman, Ian J.', 'Burkhard, Peter', 'McLeod, Rima']",NPJ Vaccines,,,True
881d4ffd2d9422f853b3140e834479d6d6db79b3,PMC,Effectiveness of a fluid chart in outpatient management of suspected dengue fever: A pilot study,http://dx.doi.org/10.1371/journal.pone.0183544,PMC5627892,28977019,CC BY,"INTRODUCTION: Dengue infection is the fastest spreading mosquito-borne viral disease in the world. One of the complications of dengue is dehydration which, if not carefully monitored and treated, may lead to shock, particularly in those with dengue haemorrhagic fever. WHO has recommended oral fluid intake of five glasses or more for adults who are suspected to have dengue fever. However, there have been no published studies looking at self-care intervention measures to improve oral fluid intake among patients suspected of dengue fever. OBJECTIVE: To assess the feasibility and effectiveness of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting. METHODS: This feasibility study used a randomized controlled study design. The data was collected over two months at a primary care clinic in a teaching hospital. The inclusion criteria were: age > 12 years, patients who were suspected to have dengue fever based on the assessment by the primary healthcare clinician, fever for > three days, and thrombocytopenia (platelets < 150 x 10(9)/L). Both groups received a dengue home care card. The intervention group received the fluid chart and a cup (200ml). Baseline clinical and laboratory data, 24-hour fluid recall (control group), and fluid chart were collected. The main outcomes were: hospitalization rates, intravenous fluid requirement and total oral fluid intake. FINDINGS: Among the 138 participants who were included in the final analysis, there were fewer hospital admissions in the intervention group (n = 7, 10.0%) than the control group (n = 12, 17.6%) (p = 0.192). Similarly, fewer patients (n = 9, 12.9%) in the intervention group required intravenous fluid compared to the control group (n = 15, 22.1%), (p = 0.154). There was an increase in the amount of daily oral fluid intake in the intervention group (about 3,000 ml) compared to the control group (about 2,500 ml, p = 0.521). However, these differences did not reach statistical significance. CONCLUSION: This is a feasible and acceptable study to perform in a primary care setting. The fluid chart is a simple, inexpensive tool that may reduce hospitalization and intravenous fluid requirement in suspected dengue patients. A randomized controlled trial with larger sample size is needed to determine this conclusively. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) Registry ISRCTN25394628 http://www.isrctn.com/ISRCTN25394628",2017 Oct 4,"['Nasir, Nazrila Hairin', 'Mohamad, Mohazmi', 'Lum, Lucy Chai See', 'Ng, Chirk Jenn']",PLoS One,,,True
d683ea2a89dfe2a07a34b35c88be26728ffc23c9,PMC,Effectiveness of a fluid chart in outpatient management of suspected dengue fever: A pilot study,http://dx.doi.org/10.1371/journal.pone.0183544,PMC5627892,28977019,CC BY,"INTRODUCTION: Dengue infection is the fastest spreading mosquito-borne viral disease in the world. One of the complications of dengue is dehydration which, if not carefully monitored and treated, may lead to shock, particularly in those with dengue haemorrhagic fever. WHO has recommended oral fluid intake of five glasses or more for adults who are suspected to have dengue fever. However, there have been no published studies looking at self-care intervention measures to improve oral fluid intake among patients suspected of dengue fever. OBJECTIVE: To assess the feasibility and effectiveness of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting. METHODS: This feasibility study used a randomized controlled study design. The data was collected over two months at a primary care clinic in a teaching hospital. The inclusion criteria were: age > 12 years, patients who were suspected to have dengue fever based on the assessment by the primary healthcare clinician, fever for > three days, and thrombocytopenia (platelets < 150 x 10(9)/L). Both groups received a dengue home care card. The intervention group received the fluid chart and a cup (200ml). Baseline clinical and laboratory data, 24-hour fluid recall (control group), and fluid chart were collected. The main outcomes were: hospitalization rates, intravenous fluid requirement and total oral fluid intake. FINDINGS: Among the 138 participants who were included in the final analysis, there were fewer hospital admissions in the intervention group (n = 7, 10.0%) than the control group (n = 12, 17.6%) (p = 0.192). Similarly, fewer patients (n = 9, 12.9%) in the intervention group required intravenous fluid compared to the control group (n = 15, 22.1%), (p = 0.154). There was an increase in the amount of daily oral fluid intake in the intervention group (about 3,000 ml) compared to the control group (about 2,500 ml, p = 0.521). However, these differences did not reach statistical significance. CONCLUSION: This is a feasible and acceptable study to perform in a primary care setting. The fluid chart is a simple, inexpensive tool that may reduce hospitalization and intravenous fluid requirement in suspected dengue patients. A randomized controlled trial with larger sample size is needed to determine this conclusively. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) Registry ISRCTN25394628 http://www.isrctn.com/ISRCTN25394628",2017 Oct 4,"['Nasir, Nazrila Hairin', 'Mohamad, Mohazmi', 'Lum, Lucy Chai See', 'Ng, Chirk Jenn']",PLoS One,,,False
743acd65106bf269a9ce56b7327e6291a65816a7,PMC,Effectiveness of a fluid chart in outpatient management of suspected dengue fever: A pilot study,http://dx.doi.org/10.1371/journal.pone.0183544,PMC5627892,28977019,CC BY,"INTRODUCTION: Dengue infection is the fastest spreading mosquito-borne viral disease in the world. One of the complications of dengue is dehydration which, if not carefully monitored and treated, may lead to shock, particularly in those with dengue haemorrhagic fever. WHO has recommended oral fluid intake of five glasses or more for adults who are suspected to have dengue fever. However, there have been no published studies looking at self-care intervention measures to improve oral fluid intake among patients suspected of dengue fever. OBJECTIVE: To assess the feasibility and effectiveness of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting. METHODS: This feasibility study used a randomized controlled study design. The data was collected over two months at a primary care clinic in a teaching hospital. The inclusion criteria were: age > 12 years, patients who were suspected to have dengue fever based on the assessment by the primary healthcare clinician, fever for > three days, and thrombocytopenia (platelets < 150 x 10(9)/L). Both groups received a dengue home care card. The intervention group received the fluid chart and a cup (200ml). Baseline clinical and laboratory data, 24-hour fluid recall (control group), and fluid chart were collected. The main outcomes were: hospitalization rates, intravenous fluid requirement and total oral fluid intake. FINDINGS: Among the 138 participants who were included in the final analysis, there were fewer hospital admissions in the intervention group (n = 7, 10.0%) than the control group (n = 12, 17.6%) (p = 0.192). Similarly, fewer patients (n = 9, 12.9%) in the intervention group required intravenous fluid compared to the control group (n = 15, 22.1%), (p = 0.154). There was an increase in the amount of daily oral fluid intake in the intervention group (about 3,000 ml) compared to the control group (about 2,500 ml, p = 0.521). However, these differences did not reach statistical significance. CONCLUSION: This is a feasible and acceptable study to perform in a primary care setting. The fluid chart is a simple, inexpensive tool that may reduce hospitalization and intravenous fluid requirement in suspected dengue patients. A randomized controlled trial with larger sample size is needed to determine this conclusively. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) Registry ISRCTN25394628 http://www.isrctn.com/ISRCTN25394628",2017 Oct 4,"['Nasir, Nazrila Hairin', 'Mohamad, Mohazmi', 'Lum, Lucy Chai See', 'Ng, Chirk Jenn']",PLoS One,,,False
3d0778430adbbbc96d00837831f9a1ce1d4ff35b,PMC,"Cloning, Assembly, and Modification of the Primary Human Cytomegalovirus Isolate Toledo by Yeast-Based Transformation-Associated Recombination",http://dx.doi.org/10.1128/mSphereDirect.00331-17,PMC5628293,28989973,CC BY,"Genetic engineering of cytomegalovirus (CMV) currently relies on generating a bacterial artificial chromosome (BAC) by introducing a bacterial origin of replication into the viral genome using in vivo recombination in virally infected tissue culture cells. However, this process is inefficient, results in adaptive mutations, and involves deletion of viral genes to avoid oversized genomes when inserting the BAC cassette. Moreover, BAC technology does not permit the simultaneous manipulation of multiple genome loci and cannot be used to construct synthetic genomes. To overcome these limitations, we adapted synthetic biology tools to clone CMV genomes in Saccharomyces cerevisiae. Using an early passage of the human CMV isolate Toledo, we first applied transformation-associated recombination (TAR) to clone 16 overlapping fragments covering the entire Toledo genome in Saccharomyces cerevisiae. Then, we assembled these fragments by TAR in a stepwise process until the entire genome was reconstituted in yeast. Since next-generation sequence analysis revealed that the low-passage-number isolate represented a mixture of parental and fibroblast-adapted genomes, we selectively modified individual DNA fragments of fibroblast-adapted Toledo (Toledo-F) and again used TAR assembly to recreate parental Toledo (Toledo-P). Linear, full-length HCMV genomes were transfected into human fibroblasts to recover virus. Unlike Toledo-F, Toledo-P displayed characteristics of primary isolates, including broad cellular tropism in vitro and the ability to establish latency and reactivation in humanized mice. Our novel strategy thus enables de novo cloning of CMV genomes, more-efficient genome-wide engineering, and the generation of viral genomes that are partially or completely derived from synthetic DNA. IMPORTANCE The genomes of large DNA viruses, such as human cytomegalovirus (HCMV), are difficult to manipulate using current genetic tools, and at this time, it is not possible to obtain, molecular clones of CMV without extensive tissue culture. To overcome these limitations, we used synthetic biology tools to capture genomic fragments from viral DNA and assemble full-length genomes in yeast. Using an early passage of the HCMV isolate Toledo containing a mixture of wild-type and tissue culture-adapted virus. we directly cloned the majority sequence and recreated the minority sequence by simultaneous modification of multiple genomic regions. Thus, our novel approach provides a paradigm to not only efficiently engineer HCMV and other large DNA viruses on a genome-wide scale but also facilitates the cloning and genetic manipulation of primary isolates and provides a pathway to generating entirely synthetic genomes.",2017 Oct 4,"['Vashee, Sanjay', 'Stockwell, Timothy B.', 'Alperovich, Nina', 'Denisova, Evgeniya A.', 'Gibson, Daniel G.', 'Cady, Kyle C.', 'Miller, Kristofer', 'Kannan, Krishna', 'Malouli, Daniel', 'Crawford, Lindsey B.', 'Voorhies, Alexander A.', 'Bruening, Eric', 'Caposio, Patrizia', 'Früh, Klaus']",mSphere,,,True
4fc52a3c9d5b8aa4b8ccc240848921d9bb560fe8,PMC,"Cloning, Assembly, and Modification of the Primary Human Cytomegalovirus Isolate Toledo by Yeast-Based Transformation-Associated Recombination",http://dx.doi.org/10.1128/mSphereDirect.00331-17,PMC5628293,28989973,CC BY,"Genetic engineering of cytomegalovirus (CMV) currently relies on generating a bacterial artificial chromosome (BAC) by introducing a bacterial origin of replication into the viral genome using in vivo recombination in virally infected tissue culture cells. However, this process is inefficient, results in adaptive mutations, and involves deletion of viral genes to avoid oversized genomes when inserting the BAC cassette. Moreover, BAC technology does not permit the simultaneous manipulation of multiple genome loci and cannot be used to construct synthetic genomes. To overcome these limitations, we adapted synthetic biology tools to clone CMV genomes in Saccharomyces cerevisiae. Using an early passage of the human CMV isolate Toledo, we first applied transformation-associated recombination (TAR) to clone 16 overlapping fragments covering the entire Toledo genome in Saccharomyces cerevisiae. Then, we assembled these fragments by TAR in a stepwise process until the entire genome was reconstituted in yeast. Since next-generation sequence analysis revealed that the low-passage-number isolate represented a mixture of parental and fibroblast-adapted genomes, we selectively modified individual DNA fragments of fibroblast-adapted Toledo (Toledo-F) and again used TAR assembly to recreate parental Toledo (Toledo-P). Linear, full-length HCMV genomes were transfected into human fibroblasts to recover virus. Unlike Toledo-F, Toledo-P displayed characteristics of primary isolates, including broad cellular tropism in vitro and the ability to establish latency and reactivation in humanized mice. Our novel strategy thus enables de novo cloning of CMV genomes, more-efficient genome-wide engineering, and the generation of viral genomes that are partially or completely derived from synthetic DNA. IMPORTANCE The genomes of large DNA viruses, such as human cytomegalovirus (HCMV), are difficult to manipulate using current genetic tools, and at this time, it is not possible to obtain, molecular clones of CMV without extensive tissue culture. To overcome these limitations, we used synthetic biology tools to capture genomic fragments from viral DNA and assemble full-length genomes in yeast. Using an early passage of the HCMV isolate Toledo containing a mixture of wild-type and tissue culture-adapted virus. we directly cloned the majority sequence and recreated the minority sequence by simultaneous modification of multiple genomic regions. Thus, our novel approach provides a paradigm to not only efficiently engineer HCMV and other large DNA viruses on a genome-wide scale but also facilitates the cloning and genetic manipulation of primary isolates and provides a pathway to generating entirely synthetic genomes.",2017 Oct 4,"['Vashee, Sanjay', 'Stockwell, Timothy B.', 'Alperovich, Nina', 'Denisova, Evgeniya A.', 'Gibson, Daniel G.', 'Cady, Kyle C.', 'Miller, Kristofer', 'Kannan, Krishna', 'Malouli, Daniel', 'Crawford, Lindsey B.', 'Voorhies, Alexander A.', 'Bruening, Eric', 'Caposio, Patrizia', 'Früh, Klaus']",mSphere,,,False
3c7ba3148349c123a012a41786a9053c1ecfd7c1,PMC,"Cloning, Assembly, and Modification of the Primary Human Cytomegalovirus Isolate Toledo by Yeast-Based Transformation-Associated Recombination",http://dx.doi.org/10.1128/mSphereDirect.00331-17,PMC5628293,28989973,CC BY,"Genetic engineering of cytomegalovirus (CMV) currently relies on generating a bacterial artificial chromosome (BAC) by introducing a bacterial origin of replication into the viral genome using in vivo recombination in virally infected tissue culture cells. However, this process is inefficient, results in adaptive mutations, and involves deletion of viral genes to avoid oversized genomes when inserting the BAC cassette. Moreover, BAC technology does not permit the simultaneous manipulation of multiple genome loci and cannot be used to construct synthetic genomes. To overcome these limitations, we adapted synthetic biology tools to clone CMV genomes in Saccharomyces cerevisiae. Using an early passage of the human CMV isolate Toledo, we first applied transformation-associated recombination (TAR) to clone 16 overlapping fragments covering the entire Toledo genome in Saccharomyces cerevisiae. Then, we assembled these fragments by TAR in a stepwise process until the entire genome was reconstituted in yeast. Since next-generation sequence analysis revealed that the low-passage-number isolate represented a mixture of parental and fibroblast-adapted genomes, we selectively modified individual DNA fragments of fibroblast-adapted Toledo (Toledo-F) and again used TAR assembly to recreate parental Toledo (Toledo-P). Linear, full-length HCMV genomes were transfected into human fibroblasts to recover virus. Unlike Toledo-F, Toledo-P displayed characteristics of primary isolates, including broad cellular tropism in vitro and the ability to establish latency and reactivation in humanized mice. Our novel strategy thus enables de novo cloning of CMV genomes, more-efficient genome-wide engineering, and the generation of viral genomes that are partially or completely derived from synthetic DNA. IMPORTANCE The genomes of large DNA viruses, such as human cytomegalovirus (HCMV), are difficult to manipulate using current genetic tools, and at this time, it is not possible to obtain, molecular clones of CMV without extensive tissue culture. To overcome these limitations, we used synthetic biology tools to capture genomic fragments from viral DNA and assemble full-length genomes in yeast. Using an early passage of the HCMV isolate Toledo containing a mixture of wild-type and tissue culture-adapted virus. we directly cloned the majority sequence and recreated the minority sequence by simultaneous modification of multiple genomic regions. Thus, our novel approach provides a paradigm to not only efficiently engineer HCMV and other large DNA viruses on a genome-wide scale but also facilitates the cloning and genetic manipulation of primary isolates and provides a pathway to generating entirely synthetic genomes.",2017 Oct 4,"['Vashee, Sanjay', 'Stockwell, Timothy B.', 'Alperovich, Nina', 'Denisova, Evgeniya A.', 'Gibson, Daniel G.', 'Cady, Kyle C.', 'Miller, Kristofer', 'Kannan, Krishna', 'Malouli, Daniel', 'Crawford, Lindsey B.', 'Voorhies, Alexander A.', 'Bruening, Eric', 'Caposio, Patrizia', 'Früh, Klaus']",mSphere,,,False
ee019cb6808f738c245cc9de12b08a19951ef594,PMC,HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways,http://dx.doi.org/10.1371/journal.ppat.1006658,PMC5629035,28945802,CC BY,"Hepatitis B virus (HBV) core protein assembles viral pre-genomic (pg) RNA and DNA polymerase into nucleocapsids for reverse transcriptional DNA replication to take place. Several chemotypes of small molecules, including heteroaryldihydropyrimidines (HAPs) and sulfamoylbenzamides (SBAs), have been discovered to allosterically modulate core protein structure and consequentially alter the kinetics and pathway of core protein assembly, resulting in formation of irregularly-shaped core protein aggregates or “empty” capsids devoid of pre-genomic RNA and viral DNA polymerase. Interestingly, in addition to inhibiting nucleocapsid assembly and subsequent viral genome replication, we have now demonstrated that HAPs and SBAs differentially modulate the biosynthesis of covalently closed circular (ccc) DNA from de novo infection and intracellular amplification pathways by inducing disassembly of nucleocapsids derived from virions as well as double-stranded DNA-containing progeny nucleocapsids in the cytoplasm. Specifically, the mistimed cuing of nucleocapsid uncoating prevents cccDNA formation during de novo infection of hepatocytes, while transiently accelerating cccDNA synthesis from cytoplasmic progeny nucleocapsids. Our studies indicate that elongation of positive-stranded DNA induces structural changes of nucleocapsids, which confers ability of mature nucleocapsids to bind CpAMs and triggers its disassembly. Understanding the molecular mechanism underlying the dual effects of the core protein allosteric modulators on nucleocapsid assembly and disassembly will facilitate the discovery of novel core protein-targeting antiviral agents that can more efficiently suppress cccDNA synthesis and cure chronic hepatitis B.",2017 Sep 25,"['Guo, Fang', 'Zhao, Qiong', 'Sheraz, Muhammad', 'Cheng, Junjun', 'Qi, Yonghe', 'Su, Qing', 'Cuconati, Andrea', 'Wei, Lai', 'Du, Yanming', 'Li, Wenhui', 'Chang, Jinhong', 'Guo, Ju-Tao']",PLoS Pathog,,,True
12329a694934f5824e1ef7d695a7a1fa0310f52c,PMC,DRREP: deep ridge regressed epitope predictor,http://dx.doi.org/10.1186/s12864-017-4024-8,PMC5629616,28984193,CC BY,"INTRODUCTION: The ability to predict epitopes plays an enormous role in vaccine development in terms of our ability to zero in on where to do a more thorough in-vivo analysis of the protein in question. Though for the past decade there have been numerous advancements and improvements in epitope prediction, on average the best benchmark prediction accuracies are still only around 60%. New machine learning algorithms have arisen within the domain of deep learning, text mining, and convolutional networks. This paper presents a novel analytically trained and string kernel using deep neural network, which is tailored for continuous epitope prediction, called: Deep Ridge Regressed Epitope Predictor (DRREP). RESULTS: DRREP was tested on long protein sequences from the following datasets: SARS, Pellequer, HIV, AntiJen, and SEQ194. DRREP was compared to numerous state of the art epitope predictors, including the most recently published predictors called LBtope and DMNLBE. Using area under ROC curve (AUC), DRREP achieved a performance improvement over the best performing predictors on SARS (13.7%), HIV (8.9%), Pellequer (1.5%), and SEQ194 (3.1%), with its performance being matched only on the AntiJen dataset, by the LBtope predictor, where both DRREP and LBtope achieved an AUC of 0.702. CONCLUSION: DRREP is an analytically trained deep neural network, thus capable of learning in a single step through regression. By combining the features of deep learning, string kernels, and convolutional networks, the system is able to perform residue-by-residue prediction of continues epitopes with higher accuracy than the current state of the art predictors.",2017 Oct 3,"['Sher, Gene', 'Zhi, Degui', 'Zhang, Shaojie']",BMC Genomics,,,True
96feece020f44e5c14a7c30ef9de6c5086299eb1,PMC,Limitations of using feline coronavirus spike protein gene mutations to diagnose feline infectious peritonitis,http://dx.doi.org/10.1186/s13567-017-0467-9,PMC5629788,28982390,CC BY,"Feline infectious peritonitis (FIP) is a fatal disease of cats, and a sequela of systemic feline coronavirus (FCoV) infection. Mutations in the viral spike (S) gene have been associated with FCoVs found in tissues from cats with FIP, but not FCoVs found in faeces from healthy cats, and are implicated in monocyte/macrophage tropism and systemic spread. This study was designed to determine whether S gene mutation analysis can reliably diagnose FIP. Cats were categorised as with FIP (n = 57) or without FIP (n = 45) based on gross post-mortem and histopathological examination including immunohistochemistry for FCoV antigen. RNA was purified from available tissue, fluid and faeces. Reverse-transcriptase quantitative-PCR (RT-qPCR) was performed on all samples using FCoV-specific primers, followed by sequencing of a section of the S gene on RT-qPCR positive samples. Samples were available from a total of 102 cats. Tissue, fluid, and faecal samples from cats with FIP were more likely to be FCoV RT-qPCR-positive (90.4, 78.4 and 64.6% respectively) than those from cats without FIP (7.8, 2.1 and 20% respectively). Identification of S gene mutated FCoVs as an additional step to the detection of FCoV alone, only moderately increased specificity for tissue samples (from 92.6 to 94.6%) but specificity was unchanged for fluid samples (97.9%) for FIP diagnosis; however, sensitivity was markedly decreased for tissue (from 89.8 to 80.9%) and fluid samples (from 78.4 to 60%) for FIP diagnosis. These findings demonstrate that S gene mutation analysis in FCoVs does not substantially improve the ability to diagnose FIP as compared to detection of FCoV alone. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-017-0467-9) contains supplementary material, which is available to authorized users.",2017 Oct 5,"['Barker, Emily N.', 'Stranieri, Angelica', 'Helps, Chris R.', 'Porter, Emily L.', 'Davidson, Andrew D.', 'Day, Michael J.', 'Knowles, Toby', 'Kipar, Anja', 'Tasker, Séverine']",Vet Res,,,True
ac6bfed80dfd9922eeb3124fe302d0a7b29997d2,PMC,Nanodiamond enhances immune responses in mice against recombinant HA/H7N9 protein,http://dx.doi.org/10.1186/s12951-017-0305-2,PMC5629800,28982373,CC BY,"BACKGROUND: The continuing spread of the newly emerged H7N9 virus among poultry in China, as well as the possibility of human-to-human transmission, has attracted numerous efforts to develop an effective vaccine against H7N9. The use of nanoparticles in vaccinology is inspired by the fact that most pathogens have a dimension within the nano-size range and therefore can be processed efficiently by the immune system, which leads to a potent immune response. Herein, we report a facile approach to increase antigen size to achieve not only fast but also effective responses against the recombinant HA/H7N9 protein via a simple conjugation of the protein onto the surface of nanodiamond particles. RESULTS: In this study, trimeric Haemagglutinin (H7) that is transiently expressed in N. benthamiana was purified using affinity chromatography, and its trimeric state was revealed successfully by the cross-linking reaction. The trimeric H7 solution was subsequently mixed with a nanodiamond suspension in different ratios. The successful conjugation of the trimeric H7 onto the surface of nanodiamond particles was demonstrated by the changes in size and Zeta-potential of the particles before and after protein coating, Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and Western-blot analysis. Next, biofunction of the protein-nanodiamond conjugates was screened using a haemagglutination assay. A mixture containing 5 µg of trimeric H7 and 60 µg of nanodiamond corresponds to a ratio of 1:12 (w/w) of agglutinated chicken red blood cells at HA titer of 1024, which is 512-fold higher than the HA titer of free trimeric H7. After the 2nd and 3rd immunization in mice, ELISA and Western blot analyses demonstrated that the physical mixture of trimeric H7 protein and nanodiamond (1:12, w/w) elicited statistically significant stronger H7-specific-IgG response demonstrated by higher amounts of H7N9-specific IgG (over 15.4-fold with P < 0.05 after the second immunization). CONCLUSIONS: These results indicated a potential effect inherent to nanodiamond towards modulating immune systems, which should be further evaluated and broadly applied in nanovaccine development.",2017 Oct 5,"['Pham, Ngoc Bich', 'Ho, Thuong Thi', 'Nguyen, Giang Thu', 'Le, Thuy Thi', 'Le, Ngoc Thu', 'Chang, Huan-Cheng', 'Pham, Minh Dinh', 'Conrad, Udo', 'Chu, Ha Hoang']",J Nanobiotechnology,,,True
82e600f01e9caa5ae2c03497d8454e5d10e87369,PMC,Detection and phylogenetic analyses of spike genes in porcine epidemic diarrhea virus strains circulating in China in 2016–2017,http://dx.doi.org/10.1186/s12985-017-0860-z,PMC5634871,29017599,CC BY,"BACKGROUND: Large-scale outbreaks of porcine epidemic diarrhea (PED) have re-emerged in China in recent years. However, little is known about the genetic diversity and molecular epidemiology of field strains of PED virus (PEDV) in China in 2016–2017. To address this issue, in this study, 116 diarrhea samples were collected from pig farms in 6 Chinese provinces in 2016–2017 and were detected using PCR for main porcine enteric pathogens, including PEDV, porcine deltacoronavirus (PDCoV), porcine transmissible gastroenteritis virus (TGEV) and porcine kobuvirus (PKV). In addition, the complete S genes from 11 representative PEDV strains were sequenced and analyzed. RESULTS: PCR detection showed that 52.6% (61/116) of these samples were positive for PEDV. Furthermore, sequencing results for the spike (S) genes from 11 of the epidemic PEDV strains showed 93–94% nucleotide identity and 92–93% amino acid identity with the classical CV777 strain. Compared with the CV777 vaccine strain, these strains had an insertion (A(133)), a deletion (G(155)), and a continuous 4-amino-acid insertion ((56)NNTN(59)) in the S1 region. Phylogenetic analysis based on the S gene indicated that the 11 assessed PEDV strains were genetically diverse and clustered into the G2 group. These results demonstrate that the epidemic strains of PEDV in China in 2016–2017 are mainly virulent strains that belong to the G2 group and genetically differ from the vaccine strain. Importantly, this is the first report that the samples collected in Hainan Province were positive for PEDV (59.2%, 25/42). CONCLUSIONS: To our knowledge, this article presents the first report of a virulent PEDV strain isolated from Hainan Island, China. The results of this study will contribute to the understanding of the epidemiology and genetic characteristics of PEDV in China.",2017 Oct 10,"['Zhang, Qiaoling', 'Liu, Xinsheng', 'Fang, Yuzhen', 'Zhou, Peng', 'Wang, Yonglu', 'Zhang, Yongguang']",Virol J,,,True
e33495040bf8950cd13d754656a31f9b9bdad01d,PMC,"Multiplex PCR point of care testing versus routine, laboratory-based testing in the treatment of adults with respiratory tract infections: a quasi-randomised study assessing impact on length of stay and antimicrobial use",http://dx.doi.org/10.1186/s12879-017-2784-z,PMC5635493,29017451,CC BY,"BACKGROUND: Laboratory-based respiratory pathogen (RP) results are often available too late to influence clinical decisions such as hospitalisation or antibiotic treatment due to time delay in transport of specimens and testing schedules. Ward-based i.e. point of care (POC) testing providing rapid results may alter the clinical management pathway. METHODS: FilmArray® RP polymerase chain reaction (PCR) systems were placed in three in-patient and out-patient medical areas. Patients presenting with influenza-like illness /upper respiratory tract infection +/− lower RTI were recruited between January–July 2015. FilmArray® POC testing occurred on even days of the month (intervention) or routine, laboratory-based RP PCR testing +/− atypical serology on odd days (control). The primary outcome was length of hospital stay. The secondary outcomes were impact on the use of antimicrobials, readmissions, all-cause mortality, length of ward stay and turn-around time (TAT) (time to result from admission). RESULTS: Of 606 eligible patients, 545 (89.9%) were included; 211 in the control arm and 334 in the intervention arm. 20% of control arm patients and 24% of intervention arm patients had an RP detected. POC testing was not associated with the primary outcome measure, length of stay, but reduced the TAT from 39.5 h to 19.0 h, p < 0.001. Only the prescribing decision differed between study arms, p < 0.001. When antivirals were given, the intervention was associated with a reduction in the median time to the first dose of 36 h and allowed appropriate treatment of mycoplasma infection. CONCLUSIONS: We found no association between respiratory PCR POC testing and length of stay or most of the secondary outcomes except the antimicrobial prescribing decision. This was probably due to a delay in initiating FilmArray® testing. Despite this, POC testing allowed time-critical antivirals to be given significantly faster, appropriate mycoplasma treatment and results were available considerably faster than routine, laboratory-based testing. Ward-staff of all grades performed POC testing without difficulty suggesting potential use across many divergent healthcare settings. Further studies evaluating the implementation of rapid respiratory PCR POC testing and the effect on length of stay and antimicrobial use are required. TRIAL REGISTRATION: ISRCTN10470967, Retrospectively Registered, 30/6/2015.",2017 Oct 10,"['Andrews, Denise', 'Chetty, Yumela', 'Cooper, Ben S.', 'Virk, Manjinder', 'Glass, Stephen K', 'Letters, Andrew', 'Kelly, Philip A.', 'Sudhanva, Malur', 'Jeyaratnam, Dakshika']",BMC Infect Dis,,,True
4d10ef49bd91ac16d18f53f428f4ef3acc96469a,PMC,Evolutionary and Phylogenetic Analysis of the Hepaciviruses and Pegiviruses,http://dx.doi.org/10.1093/gbe/evv202,PMC5635594,26494702,CC BY,"The known genetic diversity of the hepaciviruses and pegiviruses has increased greatly in recent years through the discovery of viruses related to hepatitis C virus and human pegivirus in bats, bovines, equines, primates, and rodents. Analysis of these new species is important for research into animal models of hepatitis C virus infection and into the zoonotic origins of human viruses. Here, we provide the first systematic phylogenetic and evolutionary analysis of these two genera at the whole-genome level. Phylogenies confirmed that hepatitis C virus is most closely related to viruses from horses whereas human pegiviruses clustered with viruses from African primates. Within each genus, several well-supported lineages were identified and viral diversity was structured by both host species and location of sampling. Recombination analyses provided evidence of interspecific recombination in hepaciviruses, but none in the pegiviruses. Putative mosaic genome structures were identified in NS5B gene region and were supported by multiple tests. The identification of interspecific recombination in the hepaciviruses represents an important evolutionary event that could be clarified by future sampling of novel viruses. We also identified parallel amino acid changes shared by distantly related lineages that infect similar types of host. Notable parallel changes were clustered in the NS3 and NS4B genes and provide a useful starting point for experimental studies of the evolution of Hepacivirus host–virus interactions.",2015 Oct 21,"['Thézé, Julien', 'Lowes, Sophia', 'Parker, Joe', 'Pybus, Oliver G.']",Genome Biol Evol,,,True
1a52cac849bdb5840d115cf513ec8cc63dc2d56c,PMC,The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3’-end processing,http://dx.doi.org/10.1371/journal.pone.0186034,PMC5636114,29020104,CC BY,"Unlike canonical pre-mRNAs, animal replication-dependent histone pre-mRNAs lack introns and are processed at the 3’-end by a mechanism distinct from cleavage and polyadenylation. They have a 3’ stem loop and histone downstream element (HDE) that are recognized by stem-loop binding protein (SLBP) and U7 snRNP, respectively. The N-terminal domain (NTD) of Lsm11, a component of U7 snRNP, interacts with FLASH NTD and these two proteins recruit the histone cleavage complex containing the CPSF-73 endonuclease for the cleavage reaction. Here, we determined crystal structures of FLASH NTD and found that it forms a coiled-coil dimer. Using solution light scattering, we characterized the stoichiometry of the FLASH NTD-Lsm11 NTD complex and found that it is a 2:1 heterotrimer, which is supported by observations from analytical ultracentrifugation and crosslinking.",2017 Oct 11,"['Aik, Wei Shen', 'Lin, Min-Han', 'Tan, Dazhi', 'Tripathy, Ashutosh', 'Marzluff, William F.', 'Dominski, Zbigniew', 'Chou, Chi-Yuan', 'Tong, Liang']",PLoS One,,,True
7080c264017e67e26a1e222507314d891b13e3f9,PMC,The Critical Role of Nonhuman Primates in Medical Research,http://dx.doi.org/10.20411/pai.v2i3.186,PMC5636196,29034361,CC BY,"The sponsors of this report endorse carefully regulated research with nonhuman primates. This research is essential to learning about the biology, treatment and prevention of diseases and conditions that cause human suffering.",2017 Aug 23,"['Friedman, Henry', 'Ator, Nancy', 'Haigwood, Nancy', 'Newsome, William', 'Allan, James S.', 'Golos, Thaddeus G.', 'Kordower, Jeff H.', 'Shade, Robert E.', 'Goldberg, Michael E.', 'Bailey, Matthew R.', 'Bianchi, Paul']",Pathog Immun,,,True
43c75c8c6a1fcb74ac151516e0cdd2a3a953d690,PMC,Collection of Viable Aerosolized Influenza Virus and Other Respiratory Viruses in a Student Health Care Center through Water-Based Condensation Growth,http://dx.doi.org/10.1128/mSphere.00251-17,PMC5636224,29034325,CC BY,"The dynamics and significance of aerosol transmission of respiratory viruses are still controversial, for the major reasons that virus aerosols are inefficiently collected by commonly used air samplers and that the collected viruses are inactivated by the collection method. Without knowledge of virus viability, infection risk analyses lack accuracy. This pilot study was performed to (i) determine whether infectious (viable) respiratory viruses in aerosols could be collected from air in a real world environment by the viable virus aerosol sampler (VIVAS), (ii) compare and contrast the efficacy of the standard bioaerosol sampler, the BioSampler, with that of the VIVAS for the collection of airborne viruses in a real world environment, and (iii) gain insights for the use of the VIVAS for respiratory virus sampling. The VIVAS operates via a water vapor condensation process to enlarge aerosolized virus particles to facilitate their capture. A variety of viable human respiratory viruses, including influenza A H1N1 and H3N2 viruses and influenza B viruses, were collected by the VIVAS located at least 2 m from seated patients, during a late-onset 2016 influenza virus outbreak. Whereas the BioSampler when operated following our optimized parameters also collected virus aerosols, it was nevertheless overall less successful based on a lower frequency of virus isolation in most cases. This side-by-side comparison highlights some limitations of past studies based on impingement-based sampling, which may have generated false-negative results due to either poor collection efficiency and/or virus inactivation due to the collection process. IMPORTANCE The significance of virus aerosols in the natural transmission of respiratory diseases has been a contentious issue, primarily because it is difficult to collect or sample virus aerosols using currently available air sampling devices. We tested a new air sampler based on water vapor condensation for efficient sampling of viable airborne respiratory viruses in a student health care center as a model of a real world environment. The new sampler outperformed the industry standard device (the SKC BioSampler) in the collection of natural virus aerosols and in maintaining virus viability. These results using the VIVAS indicate that respiratory virus aerosols are more prevalent and potentially pose a greater inhalation biohazard than previously thought. The VIVAS thus appears to be a useful apparatus for microbiology air quality tests related to the detection of viable airborne viruses.",2017 Oct 11,"['Pan, Maohua', 'Bonny, Tania S.', 'Loeb, Julia', 'Jiang, Xiao', 'Lednicky, John A.', 'Eiguren-Fernandez, Arantzazu', 'Hering, Susanne', 'Fan, Z. Hugh', 'Wu, Chang-Yu']",mSphere,,,True
031fd47b33af0e00eeb5e76c0d010df92df6bef6,PMC,Hospital resuscitation teams: a review of the risks to the healthcare worker,http://dx.doi.org/10.1186/s40560-017-0253-9,PMC5637256,29046809,CC BY,"BACKGROUND: “Code blue” events and related resuscitation efforts involve multidisciplinary bedside teams that implement specialized interventions aimed at patient revival. Activities include performing effective chest compressions, assessing and restoring a perfusing cardiac rhythm, stabilizing the airway, and treating the underlying cause of the arrest. While the existing critical care literature has appropriately focused on the patient, there has been a dearth of information discussing the various stresses to the healthcare team. This review summarizes the available literature regarding occupational risks to medical emergency teams, characterizes these risks, offers preventive strategies to healthcare workers, and highlights further research needs. METHODS: We performed a literature search of PubMed for English articles of all types (randomized controlled trials, case-control and cohort studies, case reports and series, editorials and commentaries) through September 22, 2016, discussing potential occupational hazards during resuscitation scenarios. Of the 6266 articles reviewed, 73 relevant articles were included. RESULTS: The literature search identified six potential occupational risk categories to members of the resuscitation team—infectious, electrical, musculoskeletal, chemical, irradiative, and psychological. Retrieved articles were reviewed in detail by the authors. CONCLUSION: Overall, we found there is limited evidence detailing the risks to healthcare workers performing resuscitation. We identify these risks and offer potential solutions. There are clearly numerous opportunities for further study in this field.",2017 Oct 11,"['Vindigni, Stephen M.', 'Lessing, Juan N.', 'Carlbom, David J.']",J Intensive Care,,,True
1cd13fbe0c5f59d9495581f31839cc2d547d4473,PMC,Correction to: Optimization and validation of sample preparation for metagenomic sequencing of viruses in clinical samples,http://dx.doi.org/10.1186/s40168-017-0351-x,PMC5637349,29025421,CC BY,,2017 Oct 12,"['Lewandowska, Dagmara W.', 'Zagordi, Osvaldo', 'Geissberger, Fabienne-Desirée', 'Kufner, Verena', 'Schmutz, Stefan', 'Böni, Jürg', 'Metzner, Karin J.', 'Trkola, Alexandra', 'Huber, Michael']",Microbiome,,,False
01cff21366d475b5bc294c90da89a521b510234a,PMC,"The viral aetiology of influenza-like illnesses in Kampala and Entebbe, Uganda, 2008",http://dx.doi.org/10.4102/ajlm.v2i1.65,PMC5637772,29043164,CC BY,"BACKGROUND: As the threat of zoonoses and the emergence of pandemic-prone respiratory viruses increases, there is a need to establish baseline information on the incidence of endemic pathogens in countries worldwide. OBJECTIVES: To investigate the presence of viruses associated with influenza-like illnesses (ILI) in Uganda. METHODS: A cross-sectional study was conducted in which nasopharyngeal swab specimens were collected from patients diagnosed with ILI in Kampala and Entebbe between 14 August 2008 – 15 December 2008. A multiplex polymerase chain reaction assay for detecting 12 respiratory viruses was used. RESULTS: A total of 369 patients (52.3% females) was enrolled; the median age was 6 years (range 1–70). One or more respiratory viruses were detected in 172 (46.6%) cases and their prevalence were influenza A virus (19.2%), adenovirus (8.7%), human rhinovirus A (7.9%), coronavirus OC43 (4.3%), parainfluenza virus 1 (2.7%), parainfluenza virus 3 (2.7%), influenza B virus (2.2%), respiratory syncytial virus B (2.2%), human metapneumovirus (1.4%), respiratory syncytial virus A (1.1%), parainfluenza virus 2 (0.5%) and coronavirus 229E (0.5%). There were 24 (14.0%) mixed infections. CONCLUSIONS: This study identified some of the respiratory viruses associated with ILI in Uganda. The circulation of some of the viruses was previously unknown in the study population. These results are useful in order to guide future surveillance and case management strategies involving respiratory illnesses in Uganda.",2013 Jun 24,"['Balinandi, Stephen', 'Bakamutumaho, Barnabas', 'Kayiwa, John T.', 'Ongus, Juliette', 'Oundo, Joseph', 'Awor, Anna C.', 'Lutwama, Julius J.']",Afr J Lab Med,,,True
91276b1c72c7bff1b7b796b8efaa9215519289a1,PMC,Structural host-microbiota interaction networks,http://dx.doi.org/10.1371/journal.pcbi.1005579,PMC5638203,29023448,CC BY,"Hundreds of different species colonize multicellular organisms making them “metaorganisms”. A growing body of data supports the role of microbiota in health and in disease. Grasping the principles of host-microbiota interactions (HMIs) at the molecular level is important since it may provide insights into the mechanisms of infections. The crosstalk between the host and the microbiota may help resolve puzzling questions such as how a microorganism can contribute to both health and disease. Integrated superorganism networks that consider host and microbiota as a whole–may uncover their code, clarifying perhaps the most fundamental question: how they modulate immune surveillance. Within this framework, structural HMI networks can uniquely identify potential microbial effectors that target distinct host nodes or interfere with endogenous host interactions, as well as how mutations on either host or microbial proteins affect the interaction. Furthermore, structural HMIs can help identify master host cell regulator nodes and modules whose tweaking by the microbes promote aberrant activity. Collectively, these data can delineate pathogenic mechanisms and thereby help maximize beneficial therapeutics. To date, challenges in experimental techniques limit large-scale characterization of HMIs. Here we highlight an area in its infancy which we believe will increasingly engage the computational community: predicting interactions across kingdoms, and mapping these on the host cellular networks to figure out how commensal and pathogenic microbiota modulate the host signaling and broadly cross-species consequences.",2017 Oct 12,"['Guven-Maiorov, Emine', 'Tsai, Chung-Jung', 'Nussinov, Ruth']",PLoS Comput Biol,,,True
e408e143da8a102c318c2d30be909628b96e1175,PMC,A simpler and more cost-effective peptide biosynthetic method using the truncated GST as carrier for epitope mapping,http://dx.doi.org/10.1371/journal.pone.0186097,PMC5638316,29023483,CC BY,"There is a need to develop better methods for epitope mapping and/or identification of antibody-recognizing motifs. Here, we describe improved biosynthetic peptide (BSP) method using a newly developed plasmid pXXGST-3 as vector, which has a viral E7 gene in the cloning sites of pXXGST-1. It is crucial to employ pXXGST-3 instead of pXXGST-1, since it makes use of the BSP method simpler and easier to perform, and more cost-effective for epitope mapping. These merits are embodied in two aspects: i) convenient recovery of double enzyme-digested product due to the existence of 315 bp inserted between BamH I and Sal I sites, and thus greatly reducing the production of self-ligation clones, and ii) no longer requiring control protein when screening recombinant (r-) clones expressing 8/18mer peptides by running polyacrylamide gel electrophoresis. The protocol involves the following core steps: (i) design of plus and minus strands of DNA fragments encoding overlapping 8/18mer peptides; (ii) chemical synthesis of the designed DNA fragments; (iii) development of r-clones using pXXGST-3 vector expressing each 8/18mer peptide fused with truncated GST188 protein; (iv) screening r-clones by running the cell pellets from each induced clone on SDS-PAGE gel followed by sequencing of inserted DNA fragments for each verified r-clone; and (v) Western blotting with either monoclonal antibodies or polyclonal antibodies. This improved GST188-BSP method provides a powerful alternative tool for epitope mapping.",2017 Oct 12,"['Xu, Wan-Xiang', 'Wang, Jian', 'Tang, Hai-Ping', 'Chen, Ling-Han', 'Lian, Wen-Bo', 'Zhan, Jian-Min', 'Gupta, Satish K.', 'Ji, Chao-Neng', 'Gu, Shao-Hua', 'Xie, Yi']",PLoS One,,,True
6c6e27a1a325b80e4b57ab890da40aca90737d7a,PMC,Filter quality of electret masks in filtering 14.6–594 nm aerosol particles: Effects of five decontamination methods,http://dx.doi.org/10.1371/journal.pone.0186217,PMC5638397,29023492,CC BY,"This study investigates the effects of five decontamination methods on the filter quality (q(f)) of three commercially available electret masks—N95, Gauze and Spunlace nonwoven masks. Newly developed evaluation methods, the overall filter quality (q(f,o)) and the q(f) ratio were applied to evaluate the effectiveness of decontamination methods for respirators. A scanning mobility particle sizer is utilized to measure the concentration of polydispersed particles with diameter 14.6–594 nm. The penetration of particles and pressure drop (Δp) through the mask are used to determine q(f) and q(f,o). Experimental results reveal that the most penetrating particle size (MPS) for the pre-decontaminated N95, Gauze and Spunlace masks were 118 nm, 461 nm and 279 nm, respectively, and the respective penetration rates were 2.6%, 23.2% and 70.0%. The Δp through the pretreated N95 masks was 9.2 mm H(2)O at the breathing flow rate of heavy-duty workers, exceeding the Δp values obtained through Gauze and Spunlace masks. Decontamination increased the sizes of the most penetrating particles, changing the q(f) values of all of the masks: q(f) fell as particle size increased because the penetration increased. Bleach increased the Δp of N95, but destroyed the Gauze mask. However, the use of an autoclave reduces the Δp values of both the N95 and the Gauze mask. Neither the rice cooker nor ethanol altered the Δp of the Gauze mask. Chemical decontamination methods reduced the q(f,o) values for the three electret masks. The value of q(f,o) for PM(0.1) exceeded that for PM(0.1–0.6), because particles smaller than 100 nm had lower penetration, resulting in a better q(f) for a given pressure drop. The values of q(f,o), particularly for PM(0.1), reveal that for the tested treatments and masks, physical decontamination methods are less destructive to the filter than chemical methods. Nevertheless, when purchasing new or reusing FFRs, penetration should be regarded as the priority.",2017 Oct 12,"['Lin, Tzu-Hsien', 'Chen, Chih-Chieh', 'Huang, Sheng-Hsiu', 'Kuo, Chung-Wen', 'Lai, Chane-Yu', 'Lin, Wen-Yinn']",PLoS One,,,True
a0fb59155b2afd7a18697b0444cdc0ec87b107a5,PMC,Nanoparticulate vacuolar ATPase blocker exhibits potent host-targeted antiviral activity against feline coronavirus,http://dx.doi.org/10.1038/s41598-017-13316-0,PMC5638965,29026122,CC BY,"Feline infectious peritonitis (FIP), caused by a mutated feline coronavirus, is one of the most serious and fatal viral diseases in cats. The disease remains incurable, and there is no effective vaccine available. In light of the pathogenic mechanism of feline coronavirus that relies on endosomal acidification for cytoplasmic entry, a novel vacuolar ATPase blocker, diphyllin, and its nanoformulation are herein investigated for their antiviral activity against the type II feline infectious peritonitis virus (FIPV). Experimental results show that diphyllin dose-dependently inhibits endosomal acidification in fcwf-4 cells, alters the cellular susceptibility to FIPV, and inhibits the downstream virus replication. In addition, diphyllin delivered by polymeric nanoparticles consisting of poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA) further demonstrates an improved safety profile and enhanced inhibitory activity against FIPV. In an in vitro model of antibody-dependent enhancement of FIPV infection, diphyllin nanoparticles showed a prominent antiviral effect against the feline coronavirus. In addition, the diphyllin nanoparticles were well tolerated in mice following high-dose intravenous administration. This study highlights the therapeutic potential of diphyllin and its nanoformulation for the treatment of FIP.",2017 Oct 12,"['Hu, Che-Ming Jack', 'Chang, Wei-Shan', 'Fang, Zih-Syun', 'Chen, You-Ting', 'Wang, Wen-Lin', 'Tsai, Hsiao-Han', 'Chueh, Ling-Ling', 'Takano, Tomomi', 'Hohdatsu, Tsutomu', 'Chen, Hui-Wen']",Sci Rep,,,False
467ab436fea0423f0621af047cd6e5c6dae5260e,PMC,Nanoparticulate vacuolar ATPase blocker exhibits potent host-targeted antiviral activity against feline coronavirus,http://dx.doi.org/10.1038/s41598-017-13316-0,PMC5638965,29026122,CC BY,"Feline infectious peritonitis (FIP), caused by a mutated feline coronavirus, is one of the most serious and fatal viral diseases in cats. The disease remains incurable, and there is no effective vaccine available. In light of the pathogenic mechanism of feline coronavirus that relies on endosomal acidification for cytoplasmic entry, a novel vacuolar ATPase blocker, diphyllin, and its nanoformulation are herein investigated for their antiviral activity against the type II feline infectious peritonitis virus (FIPV). Experimental results show that diphyllin dose-dependently inhibits endosomal acidification in fcwf-4 cells, alters the cellular susceptibility to FIPV, and inhibits the downstream virus replication. In addition, diphyllin delivered by polymeric nanoparticles consisting of poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA) further demonstrates an improved safety profile and enhanced inhibitory activity against FIPV. In an in vitro model of antibody-dependent enhancement of FIPV infection, diphyllin nanoparticles showed a prominent antiviral effect against the feline coronavirus. In addition, the diphyllin nanoparticles were well tolerated in mice following high-dose intravenous administration. This study highlights the therapeutic potential of diphyllin and its nanoformulation for the treatment of FIP.",2017 Oct 12,"['Hu, Che-Ming Jack', 'Chang, Wei-Shan', 'Fang, Zih-Syun', 'Chen, You-Ting', 'Wang, Wen-Lin', 'Tsai, Hsiao-Han', 'Chueh, Ling-Ling', 'Takano, Tomomi', 'Hohdatsu, Tsutomu', 'Chen, Hui-Wen']",Sci Rep,,,True
e0833a1c57d22b36db54876afb2282e00148b691,PMC,Contemporary HIV/AIDS research: Insights from knowledge management theory,http://dx.doi.org/10.1080/17290376.2017.1375426,PMC5639607,28922967,CC BY,"Knowledge management as a field is concerned with the management of knowledge, including the management of knowledge in research processes. Knowledge management theory has the potential to support research into problems such as HIV, antibiotic resistance and others, particularly in terms of aspects of scientific research related to the contribution of social science. To date, however, these challenges remain with us, and theoretical contributions that can complement natural science efforts to eradicate these problems are needed. This paper seeks to offer a theoretical contribution grounded in Kuhn’s paradigm theory of innovation, and in the argument by Lakatos that scientific research can be fundamentally non-innovative, which suggests that social science aspects of knowledge creation may hold the key to more effective biomedical innovation. Given the consequences of ongoing and emerging global crises, and the failure of knowledge systems of scientific research to solve such problems outright, this paper provides a review of theory and literature arguing for a new paradigm in scientific research, based on the development of global systems to maximise research collaborations. A global systems approach effectively includes social science theory development as an important complement to the natural sciences research process. Arguably, information technology and social media technology have developed to the point at which solutions to knowledge aggregation challenges can enable solutions to knowledge problems on a scale hitherto unimaginable. Expert and non-expert crowdsourced inputs can enable problem-solving through exponentially increasing problem-solving inputs, using the ‘crowd,’ thereby increasing collaborations dramatically. It is argued that these developments herald a new era of participatory research, or a democratisation of research, which offers new hope for solving global social problems. This paper seeks to contribute to this end, and to the recognition of the important role of social theory in the scientific research process.",2017 Sep 18,"Callaghan, Chris William",SAHARA J,,,True
05774f9508a8c3399ffb20e758f933ffadc40fbd,PMC,iLIR@viral: A web resource for LIR motif-containing proteins in viruses,http://dx.doi.org/10.1080/15548627.2017.1356978,PMC5640201,28806134,CC BY,"Macroautophagy/autophagy has been shown to mediate the selective lysosomal degradation of pathogenic bacteria and viruses (xenophagy), and to contribute to the activation of innate and adaptative immune responses. Autophagy can serve as an antiviral defense mechanism but also as a proviral process during infection. Atg8-family proteins play a central role in the autophagy process due to their ability to interact with components of the autophagy machinery as well as selective autophagy receptors and adaptor proteins. Such interactions are usually mediated through LC3-interacting region (LIR) motifs. So far, only one viral protein has been experimentally shown to have a functional LIR motif, leaving open a vast field for investigation. Here, we have developed the iLIR@viral database (http://ilir.uk/virus/) as a freely accessible web resource listing all the putative canonical LIR motifs identified in viral proteins. Additionally, we used a curated text-mining analysis of the literature to identify novel putative LIR motif-containing proteins (LIRCPs) in viruses. We anticipate that iLIR@viral will assist with elucidating the full complement of LIRCPs in viruses.",2017 Aug 14,"['Jacomin, Anne-Claire', 'Samavedam, Siva', 'Charles, Hannah', 'Nezis, Ioannis P.']",Autophagy,,,True
07ca288609eac312987db5e4e69de3c5a8b21e2a,PMC,Occurrence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) across the Gulf Corporation Council countries: Four years update,http://dx.doi.org/10.1371/journal.pone.0183850,PMC5640221,29028812,CC BY,"The emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections has become a global issue of dire concerns. MERS-CoV infections have been identified in many countries all over the world whereas high level occurrences have been documented in the Middle East and Korea. MERS-CoV is mainly spreading across the geographical region of the Middle East, especially in the Arabian Peninsula, while some imported sporadic cases were reported from the Europe, North America, Africa, and lately Asia. The prevalence of MERS-CoV infections across the Gulf Corporation Council (GCC) countries still remains unclear. Therefore, the objective of the current study was to report the prevalence of MERS-CoV in the GCC countries and to also elucidate on its demographics in the Arabian Peninsula. To date, the World Health Organization (WHO) has reported 1,797 laboratory-confirmed cases of MERS-CoV infection since June 2012, involving 687 deaths in 27 different countries worldwide. Within a time span of 4 years from June 2012 to July 2016, we collect samples form MERS-CoV infected individuals from National Guard Hospital, Riyadh, and Ministry of health Saudi Arabia and other GCC countries. Our data comprise a total of 1550 cases (67.1% male and 32.9% female). The age-specific prevalence and distribution of MERS-CoV was as follow: <20 yrs (36 cases: 3.28%), 20–39 yrs (331 cases: 30.15%), 40–59 yrs (314 cases: 28.60%), and the highest-risk elderly group aged ≥60 yrs (417 cases: 37.98%). The case distribution among GCC countries was as follows: Saudi Arabia (1441 cases: 93%), Kuwait (4 cases: 0.3%), Bahrain (1 case: 0.1%), Oman (8 cases: 0.5%), Qatar (16 cases: 1.0%), and United Arab Emirates (80 cases: 5.2%). Thus, MERS-CoV was found to be more prevalent in Saudi Arabia especially in Riyadh, where 756 cases (52.4%) were the worst hit area of the country identified, followed by the western region Makkah where 298 cases (20.6%) were recorded. This prevalence update indicates that the Arabian Peninsula, particularly Saudi Arabia, is the hardest hit region regarding the emerging MERS-CoV infections worldwide. GCC countries including Saudi Arabia now have the infrastructure in place that allows physicians and scientific community to identify and immediately respond to the potential risks posed by new outbreaks of MERS-CoV infections in the region. Given the continuum of emergence and the large magnitude of the disease in our region, more studies will be required to bolster capabilities for timely detection and effective control and prevention of MERS-CoV in our region.",2017 Oct 13,"['Aly, Mahmoud', 'Elrobh, Mohamed', 'Alzayer, Maha', 'Aljuhani, Sameera', 'Balkhy, Hanan']",PLoS One,,,True
fcdcbbe796ab99749c17b1e319deff8d727ed67e,PMC,Viscosity is an important factor of resistance to alcohol-based disinfectants by pathogens present in mucus,http://dx.doi.org/10.1038/s41598-017-13732-2,PMC5640602,29030631,CC BY,"Alcohol-based disinfectants play an important role in the prevention of healthcare-acquired infection (HAI). We investigated whether pathogens present in mucus acquire resistance to alcohol-based disinfectants, and elucidated the underlying mechanism. Both the resistance of influenza A virus and Escherichia coli to alcohol-based disinfectants or ultraviolet irradiation and the diffusion rate of ethanol were determined in artificial mucus or sputum samples obtained from 27 individuals with acute upper respiratory infection. Pathogens in mucus (artificial mucus or sputum samples) were not completely inactivated by alcohol-based disinfectants (survival rate >10%), suggesting that the alcohol-based disinfectants were ineffective. Pathogen survival and mucus viscosity were strongly correlated (correlation coefficient >0.7, P < 0.001). Additionally, the ethanol diffusion rate decreased with increasing mucus viscosity, which contributed to ethanol resistance. Pronase treatment of sputum samples significantly decreased sputum viscosity and increased the disinfectant effect (P < 0.001 for all). In contrast, complete inactivation was achieved by ultraviolet irradiation independently of mucus viscosity. Thus, mucus viscosity contributes to resistance of pathogens to alcohol-based disinfectants by decreasing the alcohol diffusion rate. These findings can provide a basis for developing new strategies, including improved disinfectants, for overcoming HAI.",2017 Oct 13,"['Hirose, Ryohei', 'Nakaya, Takaaki', 'Naito, Yuji', 'Daidoji, Tomo', 'Watanabe, Yohei', 'Yasuda, Hiroaki', 'Konishi, Hideyuki', 'Itoh, Yoshito']",Sci Rep,,,False
6aa27afc427161cdd39fe7f702b00f85bf04c5b0,PMC,Viscosity is an important factor of resistance to alcohol-based disinfectants by pathogens present in mucus,http://dx.doi.org/10.1038/s41598-017-13732-2,PMC5640602,29030631,CC BY,"Alcohol-based disinfectants play an important role in the prevention of healthcare-acquired infection (HAI). We investigated whether pathogens present in mucus acquire resistance to alcohol-based disinfectants, and elucidated the underlying mechanism. Both the resistance of influenza A virus and Escherichia coli to alcohol-based disinfectants or ultraviolet irradiation and the diffusion rate of ethanol were determined in artificial mucus or sputum samples obtained from 27 individuals with acute upper respiratory infection. Pathogens in mucus (artificial mucus or sputum samples) were not completely inactivated by alcohol-based disinfectants (survival rate >10%), suggesting that the alcohol-based disinfectants were ineffective. Pathogen survival and mucus viscosity were strongly correlated (correlation coefficient >0.7, P < 0.001). Additionally, the ethanol diffusion rate decreased with increasing mucus viscosity, which contributed to ethanol resistance. Pronase treatment of sputum samples significantly decreased sputum viscosity and increased the disinfectant effect (P < 0.001 for all). In contrast, complete inactivation was achieved by ultraviolet irradiation independently of mucus viscosity. Thus, mucus viscosity contributes to resistance of pathogens to alcohol-based disinfectants by decreasing the alcohol diffusion rate. These findings can provide a basis for developing new strategies, including improved disinfectants, for overcoming HAI.",2017 Oct 13,"['Hirose, Ryohei', 'Nakaya, Takaaki', 'Naito, Yuji', 'Daidoji, Tomo', 'Watanabe, Yohei', 'Yasuda, Hiroaki', 'Konishi, Hideyuki', 'Itoh, Yoshito']",Sci Rep,,,True
26dbe2acce338b3bbb79096eba3893d99b5398f0,PMC,"First molecular characterization of canine parvovirus strains in Sardinia, Italy",http://dx.doi.org/10.1007/s00705-017-3457-3,PMC5640725,28707272,CC BY,"Canine parvovirus type 2 (CPV-2) is responsible of acute hemorrhagic gastroenteritis in young dogs. CPV-2 emerged in 1978 in the USA, but new antigenic types, CPV-2a, 2b and 2c, have completely replaced the original type. In this study, we analyzed 81 animals collected in Sardinia, Italy. The VP2 sequence analysis of 27 positive samples showed that all antigenic CPV-2 types are circulating. CPV-2b seems to be the most widespread variant, followed by CPV-2a. Furthermore, 12 CPV-2b strains displayed further amino acid substitutions and formed a separate cluster in a phylogenetic tree, indicating regional genetic variation.",2017 Jul 14,"['Dei Giudici, S.', 'Cubeddu, T.', 'Giagu, A.', 'Sanna, G.', 'Rocca, S.', 'Oggiano, A.']",Arch Virol,,,True
1bd2f6497996fc0fccd8dffd7f84846d3d36f964,PMC,Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection,http://dx.doi.org/10.1128/JVI.01055-17,PMC5640845,28814523,CC BY,"Japanese encephalitis virus (JEV), an arthropod-borne flavivirus, is a major cause of acute viral encephalitis in humans. No approved drug is available for the specific treatment of JEV infections, and the available vaccines are not effective against all clinical JEV isolates. In the study described here, a high-throughput screening of an FDA-approved drug library for inhibitors of JEV was performed. Five hit drugs that inhibited JEV infection with a selective index of >10 were identified. The antiviral activities of these five hit drugs against other flavivirus, including Zika virus, were also validated. As three of the five hit drugs were calcium inhibitors, additional types of calcium inhibitors that confirmed that calcium is essential for JEV infection, most likely during viral replication, were utilized. Adaptive mutant analysis uncovered that replacement of Q130, located in transmembrane domain 3 of the nonstructural NS4B protein, which is relatively conserved in flaviviruses, with R or K conferred JEV resistance to manidipine, a voltage-gated Ca(2+) channel (VGCC) inhibitor, without an apparent loss of the viral growth profile. Furthermore, manidipine was indicated to protect mice against JEV-induced lethality by decreasing the viral load in the brain, while it abrogated the histopathological changes associated with JEV infection. This study provides five antiflavivirus candidates and identifies cytoplasmic calcium to be a novel antiviral target for the treatment of JEV infection. The findings reported here provide therapeutic possibilities for combating infections caused by flaviviruses. IMPORTANCE No approved therapy for the treatment of Japanese encephalitis virus infection is currently available. Repurposing of approved drugs would accelerate the development of a therapeutic stratagem. In this study, we screened a library of FDA-approved drugs and identified five hit drugs, especially calcium inhibitors, exerting antiflavivirus activity that blocked viral replication. The in vivo efficacy and toxicity of manidipine were investigated with a mouse model of JEV infection, and the viral target was identified by generating an adaptive mutant.",2017 Oct 13,"['Wang, Shaobo', 'Liu, Yang', 'Guo, Jiao', 'Wang, Peilin', 'Zhang, Leike', 'Xiao, Gengfu', 'Wang, Wei']",J Virol,,,True
f580401828d99aa0874fc10a731aa34a8cfb69b3,PMC,2L-PCA: a two-level principal component analyzer for quantitative drug design and its applications,http://dx.doi.org/10.18632/oncotarget.19757,PMC5642577,29050302,CC BY,"A two-level principal component predictor (2L-PCA) was proposed based on the principal component analysis (PCA) approach. It can be used to quantitatively analyze various compounds and peptides about their functions or potentials to become useful drugs. One level is for dealing with the physicochemical properties of drug molecules, while the other level is for dealing with their structural fragments. The predictor has the self-learning and feedback features to automatically improve its accuracy. It is anticipated that 2L-PCA will become a very useful tool for timely providing various useful clues during the process of drug development.",2017 Aug 1,"['Du, Qi-Shi', 'Wang, Shu-Qing', 'Xie, Neng-Zhong', 'Wang, Qing-Yan', 'Huang, Ri-Bo', 'Chou, Kuo-Chen']",Oncotarget,,,True
a98b5b8dcca1928cf18861dd7f0c14f48998b4ec,PMC,2L-PCA: a two-level principal component analyzer for quantitative drug design and its applications,http://dx.doi.org/10.18632/oncotarget.19757,PMC5642577,29050302,CC BY,"A two-level principal component predictor (2L-PCA) was proposed based on the principal component analysis (PCA) approach. It can be used to quantitatively analyze various compounds and peptides about their functions or potentials to become useful drugs. One level is for dealing with the physicochemical properties of drug molecules, while the other level is for dealing with their structural fragments. The predictor has the self-learning and feedback features to automatically improve its accuracy. It is anticipated that 2L-PCA will become a very useful tool for timely providing various useful clues during the process of drug development.",2017 Aug 1,"['Du, Qi-Shi', 'Wang, Shu-Qing', 'Xie, Neng-Zhong', 'Wang, Qing-Yan', 'Huang, Ri-Bo', 'Chou, Kuo-Chen']",Oncotarget,,,False
c7d6dd30a24a63898307d3d9e1dd6ca13a6cf9bd,PMC,The Role of Na/K-ATPase Signaling in Oxidative Stress Related to Obesity and Cardiovascular Disease,http://dx.doi.org/10.3390/molecules21091172,PMC5642908,27598118,CC BY,"Na/K-ATPase has been extensively studied for its ion pumping function, but, in the past several decades, has been identified as a scaffolding and signaling protein. Initially it was found that cardiotonic steroids (CTS) mediate signal transduction through the Na/K-ATPase and result in the generation of reactive oxygen species (ROS), which are also capable of initiating the signal cascade. However, in recent years, this Na/K-ATPase/ROS amplification loop has demonstrated significance in oxidative stress related disease states, including obesity, atherosclerosis, heart failure, uremic cardiomyopathy, and hypertension. The discovery of this novel oxidative stress signaling pathway, holds significant therapeutic potential for the aforementioned conditions and others that are rooted in ROS.",2016 Sep 3,"['Srikanthan, Krithika', 'Shapiro, Joseph I.', 'Sodhi, Komal']",Molecules,,,True
c28845dc44f29502a6012256075760eab1d62af0,PMC,Protective efficacy of a novel simian adenovirus vaccine against lethal MERS-CoV challenge in a transgenic human DPP4 mouse model,http://dx.doi.org/10.1038/s41541-017-0029-1,PMC5643297,29263883,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel zoonotic virus that causes severe respiratory disease in humans with a case fatality rate close to 40%, but for which no vaccines are available. Here, we evaluated the utility of ChAdOx1, a promising replication-deficient simian adenovirus vaccine vector platform with an established safety profile in humans and dromedary camels, for MERS-CoV vaccine development. Using a transgenic lethal BALB/c MERS-CoV mouse model we showed that single dose intranasal or intramuscular immunisation with ChAdOx1 MERS, encoding full-length MERS-CoV Spike glycoprotein, is highly immunogenic and confers protection against lethal viral challenge. Immunogenicity and efficacy were comparable between immunisation routes. Together these data provide support for further evaluation of ChAdOx1 MERS vaccine in humans and dromedary camels, the animal reservoir of infection.",2017 Oct 16,"['Munster, Vincent J.', 'Wells, Daniel', 'Lambe, Teresa', 'Wright, Daniel', 'Fischer, Robert J.', 'Bushmaker, Trenton', 'Saturday, Greg', 'van Doremalen, Neeltje', 'Gilbert, Sarah C.', 'de Wit, Emmie', 'Warimwe, George M.']",NPJ Vaccines,,,True
d6941e8307d78b087937f9ee4324969ef7e1b623,PMC,Efficacy of Antiviral Drugs against Feline Immunodeficiency Virus,http://dx.doi.org/10.3390/vetsci2040456,PMC5644647,29061953,CC BY,"Feline immunodeficiency virus (FIV) is one of the most common infectious agents affecting cats worldwide .FIV and human immunodeficiency virus (HIV) share many properties: both are lifelong persistent lentiviruses that are similar genetically and morphologically and both viruses propagate in T-lymphocytes, macrophages, and neural cells. Experimentally infected cats have measurable immune suppression, which sometimes progresses to an acquired immunodeficiency syndrome. A transient initial state of infection is followed by a long latent stage with low virus replication and absence of clinical signs. In the terminal stage, both viruses can cause severe immunosuppression. Thus, FIV infection in cats has become an important natural model for studying HIV infection in humans, especially for evaluation of antiviral compounds. Of particular importance for chemotherapeutic studies is the close similarity between the reverse transcriptase (RT) of FIV and HIV, which results in high in vitro susceptibility of FIV to many RT-targeted antiviral compounds used in the treatment of HIV-infected patients. Thus, the aim of this article is to provide an up-to-date review of studies on antiviral treatment of FIV, focusing on commercially available compounds for human or animal use.",2015 Dec 18,"['Hartmann, Katrin', 'Wooding, Anita', 'Bergmann, Michèle']",Vet Sci,,,True
57d7804297acdd855f4f2e2a6903cf6ca04d323e,PMC,"Synthesis and biological activity of myricetin derivatives containing 1,3,4-thiadiazole scaffold",http://dx.doi.org/10.1186/s13065-017-0336-7,PMC5645266,29086886,CC BY,"BACKGROUND: Myricetin and 1,3,4-thiadiazole derivatives were reported to exhibit favorable antiviral and antibacterial activities. Aiming to discover novel myricetin analogues with potent activities, a series of novel myricetin derivatives containing 1,3,4-thiadiazole moiety were synthesized, and their antibacterial and antiviral activities were evaluated. RESULT: Bioassay results indicated that some target compounds exhibited potential antibacterial and antiviral activities. Among them, compounds 2, 3a, 3b, 3d, 3f, 3i, 3m and 3p exhibited excellent antibacterial activities against Xanthomonas oryzae pv. Oryzae (Xoo), with EC(50) values of 42.7, 38.6, 20.8, 12.9, 22.7, 27.3, 18.3 and 29.4 μg/mL, respectively, which were better than that of thiadiazole-copper (94.9 μg/mL). Compounds 3b, 3d, 3e, 3f, 3i and 3o showed good antibacterial activities against Ralstonia solanacearum (Rs), with EC(50) values of 37.9, 72.6, 43.6, 59.6, 60.6 and 39.6 μg/mL, respectively, which were superior to that of thiadiazole-copper (131.7 μg/mL). In addition, compounds 3d, 3f, 3i and 3m showed better curative activities against tobacco mosaic virus (TMV), with EC(50) values of 152.8, 99.7, 127.1, and 167.3 μg/mL, respectively, which were better than that of ningnanmycin (211.1 μg/mL). CONCLUSIONS: A series of myricetin derivatives containing 1,3,4-thiadiazole scaffold were synthesized, and their antibacterial activities against Xoo and Rs and their antiviral activity against TMV were evaluated. Bioassays indicated that some target compounds exhibited potential antibacterial and antiviral activities. These results indicated this kind of myricetin analogues could be further studied as potential alternative templates in the search for novel antibacterial and antiviral agents. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13065-017-0336-7) contains supplementary material, which is available to authorized users.",2017 Oct 17,"['Zhong, Xinmin', 'Wang, Xiaobin', 'Chen, Lijuan', 'Ruan, Xianghui', 'Li, Qin', 'Zhang, Juping', 'Chen, Zhuo', 'Xue, Wei']",Chem Cent J,,,True
b9b2738ea98d39ed9c2080bc308e1f57dcc512d1,PMC,"Anticipation and response: pandemic influenza in Malawi, 2009",http://dx.doi.org/10.1080/16549716.2017.1341225,PMC5645665,28753109,CC BY,"Background: In 2006, Malawi developed a national influenza plan to mitigate, prevent and manage the burden of infection should an outbreak occur. In 2009, it translated its contingency plan to respond to the unfolding influenza pandemic. However, little is known of how Malawi translated its national influenza plan into response actions, or the success of these responses. Objective: To investigate how Malawi translated its preparedness plan and so broaden our understanding of the outcomes of the responses. Methods: We draw on data from 22 in-depth interviews with government policymakers and people working at a policy level in various non-governmental organisations, conducted to assess the level of preparedness and the challenges of translating this. Results: Through a number of public health initiatives, authorities developed communication strategies, strengthened influenza surveillance activities and updated overall goals in pandemic training and education. However, without influenza drills, exercises and simulations to test the plan, activating the pandemic plan, including coordinating and deploying generic infection control measures, was problematic. Responses during the pandemic were at times ‘weak and clumsy’ and failed to mirror the activities and processes highlighted in the preparedness plan. Conclusions: Participants stressed that in order to achieve a coordinated and successful response to mitigate and prevent the further transmission of pandemic influenza, good preparation was critical. The key elements which they identified as relevant for a rapid response included effective communications, robust evidence-based decision-making, strong and reliable surveillance systems and flexible public health responses. To effectively articulate a viable trajectory of pandemic responses, the potential value of simulation exercises could be given more consideration as a mean of sustaining good levels of preparedness and responses against future pandemics. These all demand a well-structured planning for and response to pandemic influenza strategy developed by a functioning scientific and policy advisory committee.",2017 Jul 28,"['Sambala, Evanson Z.', 'Manderson, Lenore']",Glob Health Action,,,True
6ef3cd7a4e284ef443c3d10514760c0c446866e0,PMC,Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification,http://dx.doi.org/10.1038/s41598-017-13836-9,PMC5647432,29044149,CC BY,"The recent outbreak of Zika virus (ZIKV) disease caused an enormous number of infections in Central and South America, and the unusual increase in the number of infants born with microcephaly associated with ZIKV infection aroused global concern. Here, we developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay using a portable device for the detection of ZIKV. The assay specifically detected ZIKV strains of both Asian and African genotypes without cross-reactivity with other arboviruses, including Dengue and Chikungunya viruses. The assay detected viral RNA at 14.5 TCID(50)/mL in virus-spiked serum or urine samples within 15 min, although it was slightly less sensitive than reference real time RT-PCR assay. We then evaluated the utility of this assay as a molecular diagnostic test using 90 plasma or serum samples and 99 urine samples collected from 120 suspected cases of arbovirus infection in the states of Paraíba and Pernambuco, Brazil in 2016. The results of this assay were consistent with those of the reference RT-PCR test. This portable RT-LAMP assay was highly specific for ZIKV, and enable rapid diagnosis of the virus infection. Our results provide new insights into ZIKV molecular diagnostics and may improve preparedness for future outbreaks.",2017 Oct 18,"['Kurosaki, Yohei', 'Martins, Danyelly Bruneska Gondim', 'Kimura, Mayuko', 'Catena, Andriu dos Santos', 'Borba, Maria Amélia Carlos Souto Maior', 'Mattos, Sandra da Silva', 'Abe, Haruka', 'Yoshikawa, Rokusuke', 'de Lima Filho, José Luiz', 'Yasuda, Jiro']",Sci Rep,,,True
8c2f3b308f203b56e322c637bd1eec3e228fa524,PMC,Molecular epidemiology of influenza B virus among hospitalized pediatric patients in Northern Italy during the 2015-16 season,http://dx.doi.org/10.1371/journal.pone.0185893,PMC5648122,29049310,CC BY,"BACKGROUND: The influenza B viruses belong to two lineages distinguished by their genetic and antigenic characteristics, which are referred to as the Yamagata and Victoria lineages, designated after their original isolates, B/Yamagata/16/88 and B/Victoria/2/87. The primary aim of this study was to evaluate the molecular characteristics of influenza B viruses circulating in a region of Northern Italy, Lombardia, during the influenza season of 2015–2016. METHODS: Influenza B virus was detected using a respiratory virus panel of assays and an influenza B-specific real-time polymerase chain reaction. The complete influenza B hemagglutinin (HA) gene was amplified and sequenced directly from clinical specimens. Phylogenetic analysis was performed using nucleotide sequences. RESULTS: A total of 71 hospitalized pediatric patients were influenza B positive. Phylogenetic analysis showed that the great majority of influenza B strains (66/71, 93.0%) belonged to the Victoria-lineage and were antigenically like vaccine strain (B/Brisbane/60/2008) included only in the quadrivalent vaccine. In the detected influenza B strains, a series of amino acid changes were observed in the antigenic regions: I117V, V124A, N129D, V146I, N197D, T199A, and A202T. However, only 2 amino acid changes were observed in the HA regions involved in receptor binding or in antibody recognition. CONCLUSIONS: All the influenza B strains identified in this study belonged to the influenza B Victoria lineage not included in the trivalent vaccine commonly used by the general population during the 2015–2016 influenza season in Italy. This indicates that protection against influenza B infection in the vaccinated population was in general very poor during the 2015–2016 influenza season.",2017 Oct 19,"['Piralla, Antonio', 'Lunghi, Giovanna', 'Ruggiero, Luca', 'Girello, Alessia', 'Bianchini, Sonia', 'Rovida, Francesca', 'Caimmi, Silvia', 'Marseglia, Gian Luigi', 'Principi, Nicola', 'Baldanti, Fausto', 'Esposito, Susanna']",PLoS One,,,True
36ce44a073e35fa159c1aa4fa86286643a6e9993,PMC,"Q&A: What are pathogens, and what have they done to and for us?",http://dx.doi.org/10.1186/s12915-017-0433-z,PMC5648414,29052511,CC BY,"Microbes are found on us, within us and around us. They inhabit virtually every environment on the planet and the bacteria carried by an average human, mostly in their gut, outnumber human cells. The vast majority of microbes are harmless to us, and many play essential roles in plant, animal and human health. Others, however, are either obligate or facultative pathogens exerting a spectrum of deleterious effects on their hosts. Infectious diseases have historically represented the most common cause of death in humans until recently, exceeding by far the toll taken by wars or famines. From the dawn of humanity and throughout history, infectious diseases have shaped human evolution, demography, migrations and history.",2017 Oct 19,"['Balloux, Francois', 'van Dorp, Lucy']",BMC Biol,,,True
b691523206f8c2fc150e5939b3136d361d193815,PMC,Exploring the psychological health of emergency dispatch centre operatives: a systematic review and narrative synthesis,http://dx.doi.org/10.7717/peerj.3735,PMC5649589,29062596,CC BY,"BACKGROUND: The study objective was to investigate and synthesize available evidence relating to the psychological health of Emergency Dispatch Centre (EDC) operatives, and to identify key stressors experienced by EDC operatives. METHODS: Eight electronic databases (Embase, PubMed, Medline, CINAHL, PsycInfo, PsycArticles, The Psychology and Behavioural Sciences Collection, and Google Scholar) were searched. All study designs were included, and no date limits were set. Studies were included if they were published in English, and explored the psychological health of any EDC operatives, across fire, police, and emergency medical services. Studies were excluded if they related solely to other emergency workers, such as police officers or paramedics. Methodological quality of included studies was assessed using checklists adapted from the Critical Appraisal Skills Programme. A narrative synthesis was conducted, using thematic analysis. RESULTS: A total of 16 articles were included in the review. Two overarching themes were identified during the narrative synthesis: ‘Organisational and Operational Factors’ and ‘Interactions with Others’. Stressors identified included being exposed to traumatic calls, lacking control over high workload, and working in under-resourced and pressured environments. Lack of support from management and providing an emotionally demanding service were additional sources of stress. Peer support and social support from friends and family were helpful in managing work-related stress. DISCUSSION: EDC operatives experience stress as a result of their work, which appears to be related to negative psychological health outcomes. Future research should explore the long-term effects of this stress, and the potential for workplace interventions to alleviate the negative impacts on psychological health. PROSPERO REGISTRATION NUMBER: CRD42014010806.",2017 Oct 17,"['Golding, Sarah E.', 'Horsfield, Claire', 'Davies, Annette', 'Egan, Bernadette', 'Jones, Martyn', 'Raleigh, Mary', 'Schofield, Patricia', 'Squires, Allison', 'Start, Kath', 'Quinn, Tom', 'Cropley, Mark']",PeerJ,,,True
90967c73d3f3e10ba8ab863b3deba3a40ca22fd1,PMC,"Enterovirus 71 protease 2A(pro) and 3C(pro) differentially inhibit the cellular endoplasmic reticulum-associated degradation (ERAD) pathway via distinct mechanisms, and enterovirus 71 hijacks ERAD component p97 to promote its replication",http://dx.doi.org/10.1371/journal.ppat.1006674,PMC5650186,28985237,CC BY,"Endoplasmic reticulum-associated degradation (ERAD) is an important function for cellular homeostasis. The mechanism of how picornavirus infection interferes with ERAD remains unclear. In this study, we demonstrated that enterovirus 71 (EV71) infection significantly inhibits cellular ERAD by targeting multiple key ERAD molecules with its proteases 2A(pro) and 3C(pro) using different mechanisms. Ubc6e was identified as the key E2 ubiquitin-conjugating enzyme in EV71 disturbed ERAD. EV71 3C(pro) cleaves Ubc6e at Q219G, Q260S, and Q273G. EV71 2A(pro) mainly inhibits the de novo synthesis of key ERAD molecules Herp and VIMP at the protein translational level. Herp differentially participates in the degradation of different glycosylated ERAD substrates α-1 antitrypsin Null Hong Kong (NHK) and the C-terminus of sonic hedgehog (SHH-C) via unknown mechanisms. p97 was identified as a host factor in EV71 replication; it redistributed and co-exists with the viral protein and other known replication-related molecules in EV71-induced replication organelles. Electron microscopy and multiple-color confocal assays also showed that EV71-induced membranous vesicles were closely associated with the endoplasmic reticulum (ER), and the ER membrane molecule RTN3 was redistributed to the viral replication complex during EV71 infection. Therefore, we propose that EV71 rearranges ER membranes and hijacks p97 from cellular ERAD to benefit its replication. These findings add to our understanding of how viruses disturb ERAD and provide potential anti-viral targets for EV71 infection.",2017 Oct 6,"['Wang, Tao', 'Wang, Bei', 'Huang, He', 'Zhang, Chongyang', 'Zhu, Yuanmei', 'Pei, Bin', 'Cheng, Chaofei', 'Sun, Lei', 'Wang, Jianwei', 'Jin, Qi', 'Zhao, Zhendong']",PLoS Pathog,,,True
193361dba84bf8c443b6ebd5ead3b3eb54d49379,PMC,Characterization and anti-inflammation role of swine IFITM3 gene,http://dx.doi.org/10.18632/oncotarget.20568,PMC5650283,29088728,CC BY,"IFITM3 is involved in cell adhesion, apoptosis, immune, and antivirus activity. Furthermore, IFITM3 gene has been considered as a preferential marker for inflammatory diseases, and positive correlation to pathological grades. Therefore, we assumed that IFITM3 was regulated by different signal pathways. To better understand IFITM3 function in inflammatory response, we cloned swine IFITM3 gene, and detected IFITM3 distribution in tissues, as well as characterized this gene. Results indicated that the length of swine IFITM3 gene was 438 bp, encoding 145 amino acids. IFITM3 gene expression abundance was higher in spleen and lungs. Moreover, we next constructed the eukaryotic expression vector PBIFM3 and transfected into PK15 cells, finally obtained swine IFITM3 gene stable expression cell line. Meanwhile, we explored the effects of LPS on swine IFITM3 expression. Results showed that LPS increased IFITM3 mRNA abundance and exhibited time-dependent effect for LPS treatment. To further demonstrate the mechanism that IFITM3 regulated type I IFNs production, we also detected the important molecules expression of TLR4 signaling pathway. In transfected and non-transfected IFITM3 PK15 cells, LPS exacerbated the relative expression of TLR4-NFκB signaling molecules. However, the IFITM3 overexpression suppressed the inflammatory development of PK15 cells. In conclusion, these data indicated that the overexpression of swine IFITM3 could decrease the inflammatory response through TLR4 signaling pathway, and participate in type I interferon production. These findings may lead to an improved understanding of the biological function of IFITM3 in inflammation.",2017 Aug 27,"['Li, He-Ping', 'Chen, Pei-Ge', 'Liu, Fu-Tao', 'Zhu, He-Shui', 'Jiao, Xian-Qin', 'Zhong, Kai', 'Guo, Yu-Jie', 'Zha, Guang-Ming', 'Han, Li-Qiang', 'Lu, Wei-Fei', 'Wang, Yue-Ying', 'Yang, Guo-Yu']",Oncotarget,,,True
b2d3a11928e26fbdd71764c358950fca41199fe5,PMC,Bid-deficient fish delay grass carp reovirus (GCRV) replication and attenuate GCRV-triggered apoptosis,http://dx.doi.org/10.18632/oncotarget.19460,PMC5652715,29100321,CC BY,"Bid, BH3-interacting domain death agonist, is a pro-apoptotic BH3-only member of Bcl-2 family, playing an important role in apoptosis. In the study, Bid genes from grass carp (Ctenopharyngodon idellus) and rare minnow (Gobiocypris rarus), named CiBid and GrBid, were cloned and analyzed. Bid was constitutively expressed in all examined tissues of grass carp, but the expression level varied in different tissues. Following grass carp reovirus (GCRV) stimulation in vivo, Bid and apoptosis related genes Caspase-9 and Caspase-3 was up-regulated significantly at the late stage of infection. Moreover, we generated a Bid-deficient rare minnow (Bid(-/-)) to investigate the possible role of Bid in GCRV-triggered apoptosis. We found that the survival time of Bid(-/-) rare minnow after GCRV infection was extended when compared with wild-type fish, the relative copy number of GCRV in Bid(-/-) rare minnow was lower than that in wild-type fish, and the expression level of Caspase-9 and Caspase-3 in Bid(-/-) rare minnow were significantly lower than that in the wild-type fish. Collectively, the current data revealed the important role of Bid during virus-induced apoptosis in teleost fish. Our study would provide new insight into understanding the GCRV induced apoptosis and may provide a target gene for virus-resistant breeding in grass carp.",2017 Jul 22,"['He, Libo', 'Wang, Hao', 'Luo, Lifei', 'Li, Yongming', 'Huang, Rong', 'Liao, Lanjie', 'Zhu, Zuoyan', 'Wang, Yaping']",Oncotarget,,,True
98dfad04e44035cb7f4c674eaa3886757d03088a,PMC,Bid-deficient fish delay grass carp reovirus (GCRV) replication and attenuate GCRV-triggered apoptosis,http://dx.doi.org/10.18632/oncotarget.19460,PMC5652715,29100321,CC BY,"Bid, BH3-interacting domain death agonist, is a pro-apoptotic BH3-only member of Bcl-2 family, playing an important role in apoptosis. In the study, Bid genes from grass carp (Ctenopharyngodon idellus) and rare minnow (Gobiocypris rarus), named CiBid and GrBid, were cloned and analyzed. Bid was constitutively expressed in all examined tissues of grass carp, but the expression level varied in different tissues. Following grass carp reovirus (GCRV) stimulation in vivo, Bid and apoptosis related genes Caspase-9 and Caspase-3 was up-regulated significantly at the late stage of infection. Moreover, we generated a Bid-deficient rare minnow (Bid(-/-)) to investigate the possible role of Bid in GCRV-triggered apoptosis. We found that the survival time of Bid(-/-) rare minnow after GCRV infection was extended when compared with wild-type fish, the relative copy number of GCRV in Bid(-/-) rare minnow was lower than that in wild-type fish, and the expression level of Caspase-9 and Caspase-3 in Bid(-/-) rare minnow were significantly lower than that in the wild-type fish. Collectively, the current data revealed the important role of Bid during virus-induced apoptosis in teleost fish. Our study would provide new insight into understanding the GCRV induced apoptosis and may provide a target gene for virus-resistant breeding in grass carp.",2017 Jul 22,"['He, Libo', 'Wang, Hao', 'Luo, Lifei', 'Li, Yongming', 'Huang, Rong', 'Liao, Lanjie', 'Zhu, Zuoyan', 'Wang, Yaping']",Oncotarget,,,False
5e3f2dabebc87da9fd1323d941ef57df3e7f913b,PMC,Targeting Hsp27/eIF4E interaction with phenazine compound: a promising alternative for castration-resistant prostate cancer treatment,http://dx.doi.org/10.18632/oncotarget.20469,PMC5652782,29100389,CC BY,"The actual strategy to improve current therapies in advanced prostate cancer involves targeting genes activated by androgen withdrawal, either to delay or prevent the emergence of the castration-refractory phenotype. However, these genes are often implicated in several physiological processes, and long-term inhibition of survival proteins might be accompanied with cytotoxic effects. To avoid this problem, an alternative therapeutic strategy relies on the identification and use of compounds that disrupt specific protein-protein interactions involved in androgen withdrawal. Specifically, the interaction of the chaperone protein Hsp27 with the initiation factor eIF4E leads to the protection of protein synthesis initiation process and enhances cell survival during cell stress induced by castration or chemotherapy. Thus, in this work we aimed at i) identifying the interaction site of the Hsp27/eIF4E complex and ii) interfere with the relevant protein/protein association mechanism involved in castration-resistant progression of prostate cancer. By a combination of experimental and modeling techniques, we proved that eIF4E interacts with the C-terminal part of Hsp27, preferentially when Hsp27 is phosphorylated. We also observed that the loss of this interaction increased cell chemo-and hormone-sensitivity. In order to find a potential inhibitor of Hsp27/eIF4E interaction, BRET assays in combination with molecular simulations identified the phenazine derivative 14 as the compound able to efficiently interfere with this protein/protein interaction, thereby inhibiting cell viability and increasing cell death in chemo- and castration-resistant prostate cancer models in vitro and in vivo.",2017 Aug 24,"['Ziouziou, Hajer', 'Andrieu, Claudia', 'Laurini, Erik', 'Karaki, Sara', 'Fermeglia, Maurizio', 'Oueslati, Ridha', 'Taieb, David', 'Camplo, Michel', 'Siri, Olivier', 'Pricl, Sabrina', 'Katsogiannou, Maria', 'Rocchi, Palma']",Oncotarget,,,True
0977f51bf118077aae3d344adbe019c40622beb4,PMC,Targeting Hsp27/eIF4E interaction with phenazine compound: a promising alternative for castration-resistant prostate cancer treatment,http://dx.doi.org/10.18632/oncotarget.20469,PMC5652782,29100389,CC BY,"The actual strategy to improve current therapies in advanced prostate cancer involves targeting genes activated by androgen withdrawal, either to delay or prevent the emergence of the castration-refractory phenotype. However, these genes are often implicated in several physiological processes, and long-term inhibition of survival proteins might be accompanied with cytotoxic effects. To avoid this problem, an alternative therapeutic strategy relies on the identification and use of compounds that disrupt specific protein-protein interactions involved in androgen withdrawal. Specifically, the interaction of the chaperone protein Hsp27 with the initiation factor eIF4E leads to the protection of protein synthesis initiation process and enhances cell survival during cell stress induced by castration or chemotherapy. Thus, in this work we aimed at i) identifying the interaction site of the Hsp27/eIF4E complex and ii) interfere with the relevant protein/protein association mechanism involved in castration-resistant progression of prostate cancer. By a combination of experimental and modeling techniques, we proved that eIF4E interacts with the C-terminal part of Hsp27, preferentially when Hsp27 is phosphorylated. We also observed that the loss of this interaction increased cell chemo-and hormone-sensitivity. In order to find a potential inhibitor of Hsp27/eIF4E interaction, BRET assays in combination with molecular simulations identified the phenazine derivative 14 as the compound able to efficiently interfere with this protein/protein interaction, thereby inhibiting cell viability and increasing cell death in chemo- and castration-resistant prostate cancer models in vitro and in vivo.",2017 Aug 24,"['Ziouziou, Hajer', 'Andrieu, Claudia', 'Laurini, Erik', 'Karaki, Sara', 'Fermeglia, Maurizio', 'Oueslati, Ridha', 'Taieb, David', 'Camplo, Michel', 'Siri, Olivier', 'Pricl, Sabrina', 'Katsogiannou, Maria', 'Rocchi, Palma']",Oncotarget,,,True
08e6541bee1b67eab1918bcbbe6f90463ecb651a,PMC,"Molecular characterization of infectious bronchitis viruses isolated from broiler flocks in Bushehr province, Iran: 2014 - 2015",,PMC5653882,29085606,CC BY,"The aim of this study was to provide information on the molecular characteristic and the phylogenic relationship of infectious bronchitis viruses (IBV) strains in Bushehr province in comparison to other strains reported in the Middle East. Samples were collected from broiler flocks in Bushehr province during 2014 - 2015. These flocks had respiratory problems such as gasping, sneezing and bronchial rales. A number of 135 tracheal swabs were taken from fifteen flocks (nine swabs per flock). Each three swabs collected from each flock were pooled in one tube (finally, we had three tubes for each flock). The samples were subjected to reverse transcription polymerase chain reaction (RT-PCR). The PCR products of positive samples were analyzed by sequencing of a (392 bp) segment of the spike gene and the related results were compared with the other IBV sequences in GenBank database. Samples from twelve farms (80.0%) were found to be positive. The viruses from seven farms (46.6%) were identified as field viruses closely related to variant 2. The viruses from three farms (20.0%) were characterized as Mass type and were related to vaccine strains. Two different IB viruses (variant 2 and Mass) were detected in samples from two farms (13.3%). The variant 2 genotype detected in Bushehr had high similarity to variant 2 reported from the Middle East. These variants displayed homologies ranging from 72.9% to 76.5%, and 78.8% to 80.0% with H120 and 4/91, respectively. It is necessary to design vaccination program of poultry farms using IBV strains circulating in the region.",2017 Sep 15 Summer,"['Saadat, Yousef', 'Bozorgmehri Fard, Mohammad Hassan', 'Charkhkar, Saied', 'Hosseini, Hossein', 'Shaikhi, Nariman', 'Akbarpour, Bijan']",Vet Res Forum,,,True
c736a6c9e4e639e9102e4b95136a53cd99ad2def,PMC,"Emerging and Reemerging Diseases in the World Health Organization (WHO) Eastern Mediterranean Region—Progress, Challenges, and WHO Initiatives",http://dx.doi.org/10.3389/fpubh.2017.00276,PMC5653925,29098145,CC BY,"The Eastern Mediterranean Region (EMR) of the World Health Organization (WHO) continues to be a hotspot for emerging and reemerging infectious diseases and the need to prevent, detect, and respond to any infectious diseases that pose a threat to global health security remains a priority. Many risk factors contribute in the emergence and rapid spread of epidemic diseases in the Region including acute and protracted humanitarian emergencies, resulting in fragile health systems, increased population mobility, rapid urbanization, climate change, weak surveillance and limited laboratory diagnostic capacity, and increased human–animal interaction. In EMR, several infectious disease outbreaks were detected, investigated, and rapidly contained over the past 5 years including: yellow fever in Sudan, Middle East respiratory syndrome in Bahrain, Oman, Qatar, Saudi Arabia, United Arab Emirates, and Yemen, cholera in Iraq, avian influenza A (H5N1) infection in Egypt, and dengue fever in Yemen, Sudan, and Pakistan. Dengue fever remains an important public health concern, with at least eight countries in the region being endemic for the disease. The emergence of MERS-CoV in the region in 2012 and its continued transmission currently poses one of the greatest threats. In response to the growing frequency, duration, and scale of disease outbreaks, WHO has worked closely with member states in the areas of improving public health preparedness, surveillance systems, outbreak response, and addressing critical knowledge gaps. A Regional network for experts and technical institutions has been established to facilitate support for international outbreak response. Major challenges are faced as a result of protracted humanitarian crises in the region. Funding gaps, lack of integrated approaches, weak surveillance systems, and absence of comprehensive response plans are other areas of concern. Accelerated efforts are needed by Regional countries, with the continuous support of WHO, to build and maintain a resilient public health system for detection and response to all acute public health events.",2017 Oct 19,"['Buliva, Evans', 'Elhakim, Mohamed', 'Tran Minh, Nhu Nguyen', 'Elkholy, Amgad', 'Mala, Peter', 'Abubakar, Abdinasir', 'Malik, Sk Md Mamunur Rahman']",Front Public Health,,,True
32501343a772539b8477e17940f7333e8678fe5f,PMC,"Kinetic Modelling of Infection Tracers [(18)F]FDG, [(68)Ga]Ga-Citrate, [(11)C]Methionine, and [(11)C]Donepezil in a Porcine Osteomyelitis Model",http://dx.doi.org/10.1155/2017/9256858,PMC5654273,29114181,CC BY,"INTRODUCTION: Positron emission tomography (PET) is increasingly applied for infection imaging using [(18)F]FDG as tracer, but uptake is unspecific. The present study compares the kinetics of [(18)F]FDG and three other PET tracers with relevance for infection imaging. METHODS: A juvenile porcine osteomyelitis model was used. Eleven pigs underwent PET/CT with 60-minute dynamic PET imaging of [(18)F]FDG, [(68)Ga]Ga-citrate, [(11)C]methionine, and/or [(11)C]donepezil, along with blood sampling. For infectious lesions, kinetic modelling with one- and two-tissue-compartment models was conducted for each tracer. RESULTS: Irreversible uptake was found for [(18)F]FDG and [(68)Ga]Ga-citrate; reversible uptake was found for [(11)C]methionine (two-tissue model) and [(11)C]donepezil (one-tissue model). The uptake rate for [(68)Ga]Ga-citrate was slow and diffusion-limited. For the other tracers, the uptake rate was primarily determined by perfusion (flow-limited uptake). Net uptake rate for [(18)F]FDG and distribution volume for [(11)C]methionine were significantly higher for infectious lesions than for correspondingly noninfected tissue. For [(11)C]donepezil in pigs, labelled metabolite products appeared to be important for the analysis. CONCLUSIONS: The kinetics of the four studied tracers in infection was characterized. For clinical applications, [(18)F]FDG remains the first-choice PET tracer. [(11)C]methionine may have a potential for detecting soft tissue infections. [(68)Ga]Ga-citrate and [(11)C]donepezil were not found useful for imaging of osteomyelitis.",2017 Oct 9,"['Jødal, Lars', 'Jensen, Svend B.', 'Nielsen, Ole L.', 'Afzelius, Pia', 'Borghammer, Per', 'Alstrup, Aage K. O.', 'Hansen, Søren B.']",Contrast Media Mol Imaging,,,True
753c41ab7d5d36c633e749aed6ce83334771bf7b,PMC,Global hotspots and correlates of emerging zoonotic diseases,http://dx.doi.org/10.1038/s41467-017-00923-8,PMC5654761,29066781,CC BY,"Zoonoses originating from wildlife represent a significant threat to global health, security and economic growth, and combatting their emergence is a public health priority. However, our understanding of the mechanisms underlying their emergence remains rudimentary. Here we update a global database of emerging infectious disease (EID) events, create a novel measure of reporting effort, and fit boosted regression tree models to analyze the demographic, environmental and biological correlates of their occurrence. After accounting for reporting effort, we show that zoonotic EID risk is elevated in forested tropical regions experiencing land-use changes and where wildlife biodiversity (mammal species richness) is high. We present a new global hotspot map of spatial variation in our zoonotic EID risk index, and partial dependence plots illustrating relationships between events and predictors. Our results may help to improve surveillance and long-term EID monitoring programs, and design field experiments to test underlying mechanisms of zoonotic disease emergence.",2017 Oct 24,"['Allen, Toph', 'Murray, Kris A.', 'Zambrana-Torrelio, Carlos', 'Morse, Stephen S.', 'Rondinini, Carlo', 'Di Marco, Moreno', 'Breit, Nathan', 'Olival, Kevin J.', 'Daszak, Peter']",Nat Commun,,,True
d7397d726700d9e855c8ac9650d4a32a705d86ae,PMC,Global hotspots and correlates of emerging zoonotic diseases,http://dx.doi.org/10.1038/s41467-017-00923-8,PMC5654761,29066781,CC BY,"Zoonoses originating from wildlife represent a significant threat to global health, security and economic growth, and combatting their emergence is a public health priority. However, our understanding of the mechanisms underlying their emergence remains rudimentary. Here we update a global database of emerging infectious disease (EID) events, create a novel measure of reporting effort, and fit boosted regression tree models to analyze the demographic, environmental and biological correlates of their occurrence. After accounting for reporting effort, we show that zoonotic EID risk is elevated in forested tropical regions experiencing land-use changes and where wildlife biodiversity (mammal species richness) is high. We present a new global hotspot map of spatial variation in our zoonotic EID risk index, and partial dependence plots illustrating relationships between events and predictors. Our results may help to improve surveillance and long-term EID monitoring programs, and design field experiments to test underlying mechanisms of zoonotic disease emergence.",2017 Oct 24,"['Allen, Toph', 'Murray, Kris A.', 'Zambrana-Torrelio, Carlos', 'Morse, Stephen S.', 'Rondinini, Carlo', 'Di Marco, Moreno', 'Breit, Nathan', 'Olival, Kevin J.', 'Daszak, Peter']",Nat Commun,,,False
03f3f262bea6df1ac52a601c1ea5284bc247e55a,PMC,Global hotspots and correlates of emerging zoonotic diseases,http://dx.doi.org/10.1038/s41467-017-00923-8,PMC5654761,29066781,CC BY,"Zoonoses originating from wildlife represent a significant threat to global health, security and economic growth, and combatting their emergence is a public health priority. However, our understanding of the mechanisms underlying their emergence remains rudimentary. Here we update a global database of emerging infectious disease (EID) events, create a novel measure of reporting effort, and fit boosted regression tree models to analyze the demographic, environmental and biological correlates of their occurrence. After accounting for reporting effort, we show that zoonotic EID risk is elevated in forested tropical regions experiencing land-use changes and where wildlife biodiversity (mammal species richness) is high. We present a new global hotspot map of spatial variation in our zoonotic EID risk index, and partial dependence plots illustrating relationships between events and predictors. Our results may help to improve surveillance and long-term EID monitoring programs, and design field experiments to test underlying mechanisms of zoonotic disease emergence.",2017 Oct 24,"['Allen, Toph', 'Murray, Kris A.', 'Zambrana-Torrelio, Carlos', 'Morse, Stephen S.', 'Rondinini, Carlo', 'Di Marco, Moreno', 'Breit, Nathan', 'Olival, Kevin J.', 'Daszak, Peter']",Nat Commun,,,False
ffba0e28de0ad62150f452c30641548e56503bb1,PMC,Global hotspots and correlates of emerging zoonotic diseases,http://dx.doi.org/10.1038/s41467-017-00923-8,PMC5654761,29066781,CC BY,"Zoonoses originating from wildlife represent a significant threat to global health, security and economic growth, and combatting their emergence is a public health priority. However, our understanding of the mechanisms underlying their emergence remains rudimentary. Here we update a global database of emerging infectious disease (EID) events, create a novel measure of reporting effort, and fit boosted regression tree models to analyze the demographic, environmental and biological correlates of their occurrence. After accounting for reporting effort, we show that zoonotic EID risk is elevated in forested tropical regions experiencing land-use changes and where wildlife biodiversity (mammal species richness) is high. We present a new global hotspot map of spatial variation in our zoonotic EID risk index, and partial dependence plots illustrating relationships between events and predictors. Our results may help to improve surveillance and long-term EID monitoring programs, and design field experiments to test underlying mechanisms of zoonotic disease emergence.",2017 Oct 24,"['Allen, Toph', 'Murray, Kris A.', 'Zambrana-Torrelio, Carlos', 'Morse, Stephen S.', 'Rondinini, Carlo', 'Di Marco, Moreno', 'Breit, Nathan', 'Olival, Kevin J.', 'Daszak, Peter']",Nat Commun,,,True
1477e7acddb857281705b48912ade3fd5b3f2a6e,PMC,Hepatitis A Virus: Essential Knowledge and a Novel Identify-Isolate-Inform Tool for Frontline Healthcare Providers,http://dx.doi.org/10.5811/westjem.2017.10.35983,PMC5654866,29085529,CC BY,"Infection with hepatitis A virus (HAV) causes a highly contagious illness that can lead to serious morbidity and occasional mortality. Although the overall incidence of HAV has been declining since the introduction of the HAV vaccine, there have been an increasing number of outbreaks within the United States and elsewhere between 2016 and 2017. These outbreaks have had far-reaching consequences, with a large number of patients requiring hospitalization and several deaths. Accordingly, HAV is proving to present a renewed public health challenge. Through use of the “Identify-Isolate-Inform” tool as adapted for HAV, emergency physicians can become more familiar with the identification and management of patients presenting to the emergency department (ED) with exposure, infection, or risk of contracting disease. While it can be asymptomatic, HAV typically presents with a prodrome of fever, nausea/vomiting, and abdominal pain followed by jaundice. Healthcare providers should maintain strict standard precautions for all patients suspected of having HAV infection as well as contact precautions in special cases. Hand hygiene with soap and warm water should be emphasized, and affected patients should be counseled to avoid food preparation and close contact with vulnerable populations. Additionally, ED providers should offer post-exposure prophylaxis to exposed contacts and encourage vaccination as well as other preventive measures for at-risk individuals. ED personnel should inform local public health departments of any suspected case.",2017 Oct 18,"['Koenig, Kristi L.', 'Shastry, Siri', 'Burns, Michael J.']",West J Emerg Med,,,True
57f469dc08da8f964d6c85c7d90ef62315f14e9d,PMC,High Throughput Sequencing for Detection of Foodborne Pathogens,http://dx.doi.org/10.3389/fmicb.2017.02029,PMC5655695,29104564,CC BY,"High-throughput sequencing (HTS) is becoming the state-of-the-art technology for typing of microbial isolates, especially in clinical samples. Yet, its application is still in its infancy for monitoring and outbreak investigations of foods. Here we review the published literature, covering not only bacterial but also viral and Eukaryote food pathogens, to assess the status and potential of HTS implementation to inform stakeholders, improve food safety and reduce outbreak impacts. The developments in sequencing technology and bioinformatics have outpaced the capacity to analyze and interpret the sequence data. The influence of sample processing, nucleic acid extraction and purification, harmonized protocols for generation and interpretation of data, and properly annotated and curated reference databases including non-pathogenic “natural” strains are other major obstacles to the realization of the full potential of HTS in analytical food surveillance, epidemiological and outbreak investigations, and in complementing preventive approaches for the control and management of foodborne pathogens. Despite significant obstacles, the achieved progress in capacity and broadening of the application range over the last decade is impressive and unprecedented, as illustrated with the chosen examples from the literature. Large consortia, often with broad international participation, are making coordinated efforts to cope with many of the mentioned obstacles. Further rapid progress can therefore be prospected for the next decade.",2017 Oct 20,"['Sekse, Camilla', 'Holst-Jensen, Arne', 'Dobrindt, Ulrich', 'Johannessen, Gro S.', 'Li, Weihua', 'Spilsberg, Bjørn', 'Shi, Jianxin']",Front Microbiol,,,True
9cac297cbe600d362c95485037335e959e4cf36e,PMC,"Serosurvey of Coxiella burnetii (Q fever) in Dromedary Camels (Camelus dromedarius) in Laikipia County, Kenya",http://dx.doi.org/10.1111/zph.12337,PMC5655913,28176495,CC BY,"Dromedary camels (Camelus dromedarius) are an important protein source for people in semi‐arid and arid regions of Africa. In Kenya, camel populations have grown dramatically in the past few decades resulting in the potential for increased disease transmission between humans and camels. An estimated four million Kenyans drink unpasteurized camel milk, which poses a disease risk. We evaluated the seroprevalence of a significant zoonotic pathogen, Coxiella burnetii (Q fever), among 334 camels from nine herds in Laikipia County, Kenya. Serum testing revealed 18.6% positive seroprevalence of Coxiella burnetii (n = 344). Increasing camel age was positively associated with C. burnetii seroprevalence (OR = 5.36). Our study confirmed that camels living in Laikipia County, Kenya, have been exposed to the zoonotic pathogen, C. burnetii. Further research to evaluate the role of camels in disease transmission to other livestock, wildlife and humans in Kenya should be conducted.",2017 Nov 8,"['Browne, A. S.', 'Fèvre, E. M.', 'Kinnaird, M.', 'Muloi, D. M.', 'Wang, C. A.', 'Larsen, P. S.', ""O'Brien, T."", 'Deem, S. L.']",Zoonoses Public Health,,,True
8a7647890f01aa9c0d085a1209235e832369bb44,PMC,A porcine enterovirus G associated with enteric disease contains a novel papain-like cysteine protease,http://dx.doi.org/10.1099/jgv.0.000799,PMC5656790,28590234,CC BY,"Identification of unknown pathogens in pigs displaying enteric illness is difficult due to the large diversity of bacterial and viral species found within faecal samples. Current methods often require bacterial or viral isolation, or testing only a limited number of known species using quantitative PCR analysis. Herein, faeces from two 25-day-old piglets with diarrhoea from Texas, USA, were analysed by metagenomic next-generation sequencing to rapidly identify possible pathogens. Our analysis included a bioinformatics pipeline of rapid short-read classification and de novo genome assembly which resulted in the identification of a porcine enterovirus G (EV-G), a complete genome with substantial nucleotide differences (>30 %) among current sequences, and a novel non-structural protein similar in sequence to the Torovirus papain-like cysteine protease (PL(pro)). This discovery led to the identification and circulation of an EV-G with a novel PL(pro) in the USA that has not been previously reported.",2017 Jun 8,"['Knutson, Todd P.', 'Velayudhan, Binu T.', 'Marthaler, Douglas G.']",J Gen Virol,,,True
16406822b5673734cefa5a986007b6fff662c7b5,PMC,Review article: the human intestinal virome in health and disease,http://dx.doi.org/10.1111/apt.14280,PMC5656937,28869283,CC BY,"BACKGROUND: The human virome consists of animal‐cell viruses causing transient infections, bacteriophage (phage) predators of bacteria and archaea, endogenous retroviruses and viruses causing persistent and latent infections. High‐throughput, inexpensive, sensitive sequencing methods and metagenomics now make it possible to study the contribution dsDNA, ssDNA and RNA virus‐like particles make to the human virome, and in particular the intestinal virome. AIM: To review and evaluate the pioneering studies that have attempted to characterise the human virome and generated an increased interest in understanding how the intestinal virome might contribute to maintaining health, and the pathogenesis of chronic diseases. METHODS: Relevant virome‐related articles were selected for review following extensive language‐ and date‐unrestricted, electronic searches of the literature. RESULTS: The human intestinal virome is personalised and stable, and dominated by phages. It develops soon after birth in parallel with prokaryotic communities of the microbiota, becoming established during the first few years of life. By infecting specific populations of bacteria, phages can alter microbiota structure by killing host cells or altering their phenotype, enabling phages to contribute to maintaining intestinal homeostasis or microbial imbalance (dysbiosis), and the development of chronic infectious and autoimmune diseases including HIV infection and Crohn's disease, respectively. CONCLUSIONS: Our understanding of the intestinal virome is fragmented and requires standardised methods for virus isolation and sequencing to provide a more complete picture of the virome, which is key to explaining the basis of virome‐disease associations, and how enteric viruses can contribute to disease aetiologies and be rationalised as targets for interventions.",2017 Nov 4,"['Carding, S. R.', 'Davis, N.', 'Hoyles, L.']",Aliment Pharmacol Ther,,,True
04034022f265da392051b3e3fcef2e580247d6c4,PMC,Marburg virus-like particles by co-expression of glycoprotein and matrix protein in insect cells induces immune responses in mice,http://dx.doi.org/10.1186/s12985-017-0869-3,PMC5657058,29070075,CC BY,"BACKGROUND: Marburg virus (MARV) causes severe haemorrhagic fever in humans and nonhuman primates and has a high mortality rate. However, effective drugs or licensed vaccines are not currently available to control the outbreak and spread of this disease. METHODS: In this study, we generated MARV virus-like particles (VLPs) by co-expressing the glycoprotein (GP) and matrix protein (VP40) using the baculovirus expression system. MARV VLPs and three adjuvants, Poria cocos polysaccharide (PCP-II), poly(I:C) and aluminium hydroxide, were evaluated after intramuscular vaccination in mice. RESULTS: Murine studies demonstrated that vaccination with the MARV VLPs induce neutralizing antibodies and cellar immune responses. MARV VLPs and the PCP-II adjuvant group resulted in high titres of MARV-specific antibodies, activated relatively higher numbers of B cells and T cells in peripheral blood mononuclear cells (PBMCs), and induced greater cytokine secretion from splenocytes than the other adjuvants. CONCLUSION: MARV VLPs with the PCP-II adjuvant may constitute an effective vaccination and PCP-II should be further investigated as a novel adjuvant.",2017 Oct 25,"['Gai, Weiwei', 'Zheng, Xuexing', 'Wang, Chong', 'Wang, Hualei', 'Zhao, Yongkun', 'Wang, Qi', 'Wong, Gary', 'Zhang, Weijiao', 'Feng, Na', 'Qiu, Boning', 'Chi, Hang', 'Li, Nan', 'Wang, Tiecheng', 'Gao, Yuwei', 'Shan, Junjie', 'Yang, Songtao', 'Xia, Xianzhu']",Virol J,,,True
efb09a669665f5e0e097c2d5e94c499a6e43bd9e,PMC,Yeast for virus research,http://dx.doi.org/10.15698/mic2017.10.592,PMC5657823,29082230,CC BY,"Budding yeast (Saccharomyces cerevisiae) and fission yeast (Schizosaccharomyces pombe) are two popular model organisms for virus research. They are natural hosts for viruses as they carry their own indigenous viruses. Both yeasts have been used for studies of plant, animal and human viruses. Many positive sense (+) RNA viruses and some DNA viruses replicate with various levels in yeasts, thus allowing study of those viral activities during viral life cycle. Yeasts are single cell eukaryotic organisms. Hence, many of the fundamental cellular functions such as cell cycle regulation or programed cell death are highly conserved from yeasts to higher eukaryotes. Therefore, they are particularly suited to study the impact of those viral activities on related cellular activities during virus-host interactions. Yeasts present many unique advantages in virus research over high eukaryotes. Yeast cells are easy to maintain in the laboratory with relative short doubling time. They are non-biohazardous, genetically amendable with small genomes that permit genome-wide analysis of virologic and cellular functions. In this review, similarities and differences of these two yeasts are described. Studies of virologic activities such as viral translation, viral replication and genome-wide study of virus-cell interactions in yeasts are highlighted. Impacts of viral proteins on basic cellular functions such as cell cycle regulation and programed cell death are discussed. Potential applications of using yeasts as hosts to carry out functional analysis of small viral genome and to develop high throughput drug screening platform for the discovery of antiviral drugs are presented.",,"Zhao, Richard Yuqi",Microb Cell.; 4(10):311-330,,,True
61cd0ce1029799eed2e471e0017fcac99e09fb20,PMC,National Preparedness Month — September 2017,http://dx.doi.org/10.15585/mmwr.mm6636a1,PMC5657913,,CC BY,,2017 Sep 15,,MMWR Morb Mortal Wkly Rep,,,True
442464f84846ea95f2e99df37e18a512ea513ce2,PMC,"Assessment of Hospital Emergency Department Response to Potentially Infectious Diseases Using Unannounced Mystery Patient Drills — New York City, 2016",http://dx.doi.org/10.15585/mmwr.mm6636a2,PMC5657916,28910268,CC BY,,2017 Sep 15,"['Foote, Mary M.K.', 'Styles, Timothy S.', 'Quinn, Celia L.']",MMWR Morb Mortal Wkly Rep,,,True
c8978a8074a9df4bf07e49393821886d0b80979f,PMC,"Notes from the Field: Severe Human Metapneumovirus Infections — North Dakota, 2016",http://dx.doi.org/10.15585/mmwr.mm6618a7,PMC5657983,28493852,CC BY,,2017 May 12,"['Midgley, Claire M.', 'Baber, Jill K.', 'Biggs, Holly M.', 'Singh, Twila', 'Feist, Michelle', 'Miller, Tracy K.', 'Kruger, Kirby', 'Gerber, Susan I.', 'Watson, John T.', 'Howell, Molly A.']",MMWR Morb Mortal Wkly Rep,,,True
0a05a7b95ce42f0b53c86a24842ecc9845a7d023,PMC,Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus,http://dx.doi.org/10.1371/journal.pone.0186854,PMC5658087,29073183,CC0,"Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV)—a highly prevalent childhood pathogen without a licensed vaccine—we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F) “DS-Cav1” immunogen, which induced high titer RSV-neutralizing antibodies, in mice and non-human primates, when formulated with adjuvants Poly (I:C) and Poly (IC:LC), respectively. To assess the impact of different adjuvants, here we formulated RSV F DS-Cav1 with multiple adjuvants and assessed immune responses. Very high RSV-neutralizing antibody responses (19,006 EC(50)) were observed in naïve mice immunized with 2 doses of DS-Cav1 adjuvanted with Sigma adjuvant system (SAS), an oil-in-water adjuvant, plus Carbopol; high responses (3658–7108) were observed with DS-Cav1 adjuvanted with Alum, SAS alone, Adjuplex, Poly (I:C) and Poly (IC:LC); and moderate responses (1251–2129) were observed with DS-Cav1 adjuvanted with the TLR4 agonist MPLA, Alum plus MPLA or AddaVax. In contrast, DS-Cav1 without adjuvant induced low-level responses (6). A balanced IgG1 and IgG2a (Th2/Th1) immune response was elicited in most of the high to very high response groups (all but Alum and Adjuplex). We also tested the immune response induced by DS-Cav1 in elderly mice with pre-existing DS-Cav1 immunity; we observed that DS-Cav1 adjuvanted with SAS plus Carbopol boosted the response 2-3-fold, whereas DS-Cav1 adjuvanted with alum boosted the response 5-fold. Finally, we tested whether a mixture of ISA 71 VG and Carbopol would enhanced the antibody response in DS-Cav1 immunized calves. While pre-F-stabilized bovine RSV F induced very high titers in mice when adjuvanted with SAS plus Carbopol, the addition of Carbopol to ISA 71 VG did not enhance immune responses in calves. The vaccine response to pre-F-stabilized RSV F is augmented by adjuvant, but the degree of adjuvant-induced enhancement appears to be both context-dependent and species-specific.",2017 Oct 26,"['Sastry, Mallika', 'Zhang, Baoshan', 'Chen, Man', 'Joyce, M. Gordon', 'Kong, Wing-Pui', 'Chuang, Gwo-Yu', 'Ko, Kiyoon', 'Kumar, Azad', 'Silacci, Chiara', 'Thom, Michelle', 'Salazar, Andres M.', 'Corti, Davide', 'Lanzavecchia, Antonio', 'Taylor, Geraldine', 'Mascola, John R.', 'Graham, Barney S.', 'Kwong, Peter D.']",PLoS One,,,True
6fd5ec9e4ec79f24c0bf011e388410d8ec35fe0f,PMC,Etanercept for steroid-refractory acute graft-versus-host disease: A single center experience,http://dx.doi.org/10.1371/journal.pone.0187184,PMC5658201,29073260,CC BY,"BACKGROUND: Acute graft-versus-host disease (aGVHD) is an important complication of allogeneic stem cell transplantation (alloSCT). High dose glucocorticosteroids, are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40%-50% of patients. No standard second-line regimen has been established. Different options have been reported, including anti-TNFα antibodies. METHODS: We retrospectively reviewed the outcome of 15 patients with steroid-refractory (SR) aGVHD treated with etanercept at our institution. Patients were transplanted for a hematological malignancy and received either a myeloablative or a non-myeloablative conditioning regimen. Prophylaxis of GVHD consisted of cyclosporin A and mycophenolic acid. RESULTS: Acute GVHD was diagnosed at a median of 61 days post-transplantation. All patients had grade III aGVHD of the gut. Second-line treatment with etanercept was started at a median of 13 days after initiation of first-line therapy. Overall response rate was 53%, with CR in 3 patients and PR in 5 patients. Median overall survival after initiation of treatment with etanercept was 66 days (range 5–267) for the entire group. Median overall survival was 99 days (range 47–267 days) for responders and 17 days (range 5–66 days) for non-responders (p<0.01). Nevertheless, all patients died. Causes of death were progressive GVHD in 7 patients (47%), infection in 6 patients (40%), cardiac death in 1 patient (6.7%) and relapse in 1 patient (6,7%). CONCLUSION: Second-line treatment with etanercept does induce responses in SR-aGVHD of the gut but appears to be associated with poor long-term survival even in responding patients.",2017 Oct 26,"['De Jong, Cornelis N.', 'Saes, Lotte', 'Klerk, Clara P. W.', 'Van der Klift, Marjolein', 'Cornelissen, Jan J.', 'Broers, Annoek E. C.']",PLoS One,,,True
811ba28ec90198a294812d7b1deadf16b4fc66ab,PMC,Neutralization of Zika virus by germline-like human monoclonal antibodies targeting cryptic epitopes on envelope domain III,http://dx.doi.org/10.1038/emi.2017.79,PMC5658772,29018252,CC BY,"The Zika virus (ZIKV), a flavivirus transmitted by Aedes mosquitoes, has emerged as a global public health concern. Pre-existing cross-reactive antibodies against other flaviviruses could modulate immune responses to ZIKV infection by antibody-dependent enhancement, highlighting the importance of understanding the immunogenicity of the ZIKV envelope protein. In this study, we identified a panel of human monoclonal antibodies (mAbs) that target domain III (DIII) of the ZIKV envelope protein from a very large phage-display naive antibody library. These germline-like antibodies, sharing 98%–100% hoLogy with their corresponding germline IGHV genes, bound ZIKV DIII specifically with high affinities. One mAb, m301, broadly neutralized the currently circulating ZIKV strains and showed a synergistic effect with another mAb, m302, in neutralizing ZIKV in vitro and in a mouse model of ZIKV infection. Interestingly, epitope mapping and competitive binding studies suggest that m301 and m302 bind adjacent regions of the DIII C–C′ loop, which represents a recently identified cryptic epitope that is intermittently exposed in an uncharacterized virus conformation. This study extended our understanding of antigenic epitopes of ZIKV antibodies and has direct implications for the design of ZIKV vaccines.",2017 Oct 11,"['Wu, Yanling', 'Li, Shun', 'Du, Lanying', 'Wang, Chunyu', 'Zou, Peng', 'Hong, Binbin', 'Yuan, Mengjiao', 'Ren, Xiaonan', 'Tai, Wanbo', 'Kong, Yu', 'Zhou, Chen', 'Lu, Lu', 'Zhou, Xiaohui', 'Jiang, Shibo', 'Ying, Tianlei']",Emerg Microbes Infect,,,True
3fa6e9ba72b68964da451b01a4ccf7a7842c942c,PMC,Neutralization of Zika virus by germline-like human monoclonal antibodies targeting cryptic epitopes on envelope domain III,http://dx.doi.org/10.1038/emi.2017.79,PMC5658772,29018252,CC BY,"The Zika virus (ZIKV), a flavivirus transmitted by Aedes mosquitoes, has emerged as a global public health concern. Pre-existing cross-reactive antibodies against other flaviviruses could modulate immune responses to ZIKV infection by antibody-dependent enhancement, highlighting the importance of understanding the immunogenicity of the ZIKV envelope protein. In this study, we identified a panel of human monoclonal antibodies (mAbs) that target domain III (DIII) of the ZIKV envelope protein from a very large phage-display naive antibody library. These germline-like antibodies, sharing 98%–100% hoLogy with their corresponding germline IGHV genes, bound ZIKV DIII specifically with high affinities. One mAb, m301, broadly neutralized the currently circulating ZIKV strains and showed a synergistic effect with another mAb, m302, in neutralizing ZIKV in vitro and in a mouse model of ZIKV infection. Interestingly, epitope mapping and competitive binding studies suggest that m301 and m302 bind adjacent regions of the DIII C–C′ loop, which represents a recently identified cryptic epitope that is intermittently exposed in an uncharacterized virus conformation. This study extended our understanding of antigenic epitopes of ZIKV antibodies and has direct implications for the design of ZIKV vaccines.",2017 Oct 11,"['Wu, Yanling', 'Li, Shun', 'Du, Lanying', 'Wang, Chunyu', 'Zou, Peng', 'Hong, Binbin', 'Yuan, Mengjiao', 'Ren, Xiaonan', 'Tai, Wanbo', 'Kong, Yu', 'Zhou, Chen', 'Lu, Lu', 'Zhou, Xiaohui', 'Jiang, Shibo', 'Ying, Tianlei']",Emerg Microbes Infect,,,False
39e643e0263bee019519c0c51f4ae17f1fe1a0a5,PMC,"Strategy and technology to prevent hospital-acquired infections: Lessons from SARS, Ebola, and MERS in Asia and West Africa",http://dx.doi.org/10.1186/s40779-017-0142-5,PMC5659033,29502517,CC BY,"Hospital-acquired infections (HAIs) are serious problems for healthcare systems, especially in developing countries where public health infrastructure and technology for infection preventions remain undeveloped. Here, we characterized how strategy and technology could be mobilized to improve the effectiveness of infection prevention and control in hospitals during the outbreaks of Ebola, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS) in Asia and West Africa. Published literature on the hospital-borne outbreaks of SARS, Ebola, and MERS in Asia and West Africa was comprehensively reviewed. The results showed that healthcare systems and hospital management in affected healthcare facilities had poor strategies and inadequate technologies and human resources for the prevention and control of HAIs, which led to increased morbidity, mortality, and unnecessary costs. We recommend that governments worldwide enforce disaster risk management, even when no outbreaks are imminent. Quarantine and ventilation functions should be taken into consideration in architectural design of hospitals and healthcare facilities. We also recommend that health authorities invest in training healthcare workers for disease outbreak response, as their preparedness is essential to reducing disaster risk.",2017 Oct 27,"['Rajakaruna, Sanjeewa Jayachandra', 'Liu, Wen-Bin', 'Ding, Yi-Bo', 'Cao, Guang-Wen']",Mil Med Res,,,True
a2ea85a02fee49f55f485a2b5d808636cb38a0bb,PMC,Evaluation of the efficacy of a commercial inactivated genogroup 2b-based porcine epidemic diarrhea virus (PEDV) vaccine and experimental live genogroup 1b exposure against 2b challenge,http://dx.doi.org/10.1186/s13567-017-0472-z,PMC5659040,29073936,CC BY,"Porcine epidemic diarrhea virus strains from the G1b cluster are considered less pathogenic compared to the G2b cluster. The aim of this study was to compare the ability of G1b-based live virus exposure against use of a commercial G2b–based inactivated vaccine to protect growing pigs against G2b challenge. Thirty-nine PEDV naïve pigs were randomly divided into five groups: EXP-IM-1b (intramuscular G1b exposure; G2b challenge), EXP-ORAL-1b (oral G1b exposure; G2b challenge), VAC-IM-2b (intramuscular commercial inactivated G2b vaccination; G2b challenge), POS-CONTROL (sham-vaccination; G2b challenge) and NEG-CONTROL (sham-vaccination; sham-challenge). Pigs were vaccinated/exposed at 3 weeks of age (day post-vaccination 0, dpv 0), VAC-IM-2b pigs were revaccinated at dpv 14, and the pigs were challenged at dpv 28. Among all groups, VAC-IM-2b pigs had significantly higher anti-PEDV IgG levels on dpv 21 and 28 while EXP-ORAL-1b pigs had significantly higher anti-PEDV IgA levels on dpv 14, 21, 28 and 35. EXP-ORAL-1b also had detectable IgA in feces. Intramuscular PEDV exposure did not result in a detectable antibody response in EXP-IM-1b pigs. The fecal PEDV RNA levels in VAC-IM-2b pigs were significantly lower 5–7 days after challenge compared to the POS-CONTROL group. Under the study conditions a commercial inactivated G2b-based vaccine protected pigs against G2b challenge, as evidenced by reduction of PEDV RNA in feces for 3–4 logs during peak shedding and a shorter viral shedding duration. The oral, but not the intramuscular, experimental G1b-based live virus exposure induced a high anti-PEDV IgA response prior to challenge, which apparently did not impact PEDV shedding compared to POS-CONTROL pigs.",2017 Oct 26,"['Opriessnig, Tanja', 'Gerber, Priscilla F.', 'Shen, Huigang', 'de Castro, Alessandra Marnie M. G.', 'Zhang, Jianqiang', 'Chen, Qi', 'Halbur, Patrick']",Vet Res,,,True
22bc83fbc25560c43305c1995aad1e805821e054,PMC,Reference gene selection for gene expression study in shell gland and spleen of laying hens challenged with infectious bronchitis virus,http://dx.doi.org/10.1038/s41598-017-14693-2,PMC5660252,29079779,CC BY,"Ten reference genes were investigated for normalisation of candidate target gene expression data in the shell gland and spleen of laying hens challenged with two strains of infectious bronchitis virus (IBV). Data were analysed with geNorm, NormFinder and BestKeeper, and a comprehensive ranking (geomean) was calculated. In the combined data set of IBV challenged shell gland samples, the comprehensive ranking showed TATA-box binding protein (TBP) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) as the two most stable, and succinate dehydrogenase complex flavoprotein subunit A (SDHA) and albumin (ALB) as the two least stable reference genes. In the spleen, and in the combined data set of the shell gland and spleen, the two most stable and the two least stable reference genes were TBP and YWHAZ, and ribosomal protein L4 (RPL4) and ALB, respectively. Different ranking has been due to different algorithms. Validation studies showed that the use of the two most stable reference genes produced accurate and more robust gene expression data. The two most and least stable reference genes obtained in the study, were further used for candidate target gene expression data normalisation of the shell gland and spleen under an IBV infection model.",2017 Oct 27,"['Khan, Samiullah', 'Roberts, Juliet', 'Wu, Shu-Biao']",Sci Rep,,,True
5a5dde5900813ecf3b68e226c3976cb2226ccf5b,PMC,miPepBase: A Database of Experimentally Verified Peptides Involved in Molecular Mimicry,http://dx.doi.org/10.3389/fmicb.2017.02053,PMC5660332,29109711,CC BY,"Autoimmune diseases emerge due to several reasons, of which molecular mimicry i.e., similarity between the host's and pathogen's interacting peptides is an important reason. In the present study we have reported a database of only experimentally verified peptide sequences, which exhibit molecular mimicry. The database is named as miPepBase (Mimicry Peptide Database) and contains comprehensive information about mimicry proteins and peptides of both host (and model organism) and pathogen. It also provides information about physicochemical properties of protein and mimicry peptides, which might be helpful in predicting the nature of protein and optimization of protein expression. The miPepBase can be searched using a keyword or, by autoimmune disease(s) or by a combination of host and pathogen taxonomic group or their name. To facilitate the search of proteins and/or epitope in miPepBase, which is similar to the user's interest, BLAST search tool is also incorporated. miPepBase is an open access database and available at http://proteininformatics.org/mkumar/mipepbase.",2017 Oct 23,"['Garg, Anjali', 'Kumari, Bandana', 'Kumar, Ravindra', 'Kumar, Manish']",Front Microbiol,,,True
8088d74438c31d5ca8f976c21ae9167c5c682d14,PMC,Acute Asthma in the Pediatric Emergency Department: Infections Are the Main Triggers of Exacerbations,http://dx.doi.org/10.1155/2017/9687061,PMC5660758,29159184,CC BY,"BACKGROUND: Asthma exacerbations are a common reason for Emergency Department (ED) visits in children. AIM: To analyze differences among age groups in terms of triggering factors and seasonality and to identify those with higher risk of severe exacerbations. METHODS: We retrospectively revised the files of children admitted for acute asthma in 2016 in our Pediatric ED. RESULTS: Visits for acute asthma were 603/23197 (2.6%). 76% of the patients were <6 years old and 24% ≥6. Infections were the main trigger of exacerbations in both groups; 33% of the school-aged children had a triggering allergic condition (versus 3% in <6 years; p < .01). 191 patients had a previous history of asthma; among them, 95 were ≥6 years, 67% of whom were not using any controller medication, showing a higher risk of a moderate-to-severe exacerbation than those under long-term therapy (p < .01). Exacerbations peaked in autumn and winter in preschoolers and in spring and early autumn in the school-aged children. CONCLUSIONS: Infections are the main trigger of acute asthma in children of any age, followed by allergy in the school-aged children. Efforts for an improved management of patients affected by chronic asthma might go through individualized action plans and possibly vaccinations and allergen-avoidance measures.",2017 Oct 12,"['Dondi, Arianna', 'Calamelli, Elisabetta', 'Piccinno, Valentina', 'Ricci, Giampaolo', 'Corsini, Ilaria', 'Biagi, Carlotta', 'Lanari, Marcello']",Biomed Res Int,,,True
f703b510de361a759c9fe3419fa3aeb092c95512,PMC,One Health and Zoonoses: The Evolution of One Health and Incorporation of Zoonoses,http://dx.doi.org/10.5195/cajgh.2015.139,PMC5661195,29138713,CC BY,"INTRODUCTION: Zoonotic disease outbreaks have surged in the last two decades. These include severe acute respiratory syndrome (SARS), Hendra virus, Nipah virus, influenza viruses, Middle East Respiratory Syndrome (MERS) coronavirus, and ebola. One Health is the initiative of an inclusive collaboration linking human, animal, and environmental health. One Health is advocated through an intersectoral coordination to combat zoonoses, and the term has evolved over centuries. The primary aim of this literature review was to examine the change in the definition of the term One Health over time, particuarly following the the introduction of the latest definition in 2007 by the American Medical Association and the American Veterinary Medical Association. METHODS: This review was conducted in four phases. The first phase consisted of a general PubMed search for the phrase “One Health” for every literature published up to December 2014. Then an advanced search was carried out using “One Health” in conjunction with the terms “zoonosis” and “zoonoses” in PubMed for the time period between January 2007 and December 2014. The articles found were then categorized based on the type of journals in which the articles were published. For the second phase, “One Health” was searched as a Medical subject heading (MeSH) term, which is the National Library of Medicine controlled vocabulary thesaurus used for indexing articles. In the third phase, One Health advocate organizations were found using Google search engine. During the final phase, One Health was searched in Google scholar, examined by Google trends, and analyzed by Google ngram. RESULTS: Before 2007, One Health had many connotations to health in the medical literature with an incomplete adherence to the usage of One Health linking zoonoses. The Google trends analysis shows an overal steady increase of the search of One Health from 2007 to 2014, which is consistent with the findings of articles from Pubmed. DISCUSSION: Our results indicate that the linkage between the terms One Health and zoonoses started in 2007, which correlates with the joint declaration made by the American Medical Association and the American Veterinary Medical Association in 2007. We suggest creating a MeSH term for One Health in the PubMed database to support more specific research on zoonoses, and exploring the possibility of a patent of the term One Health to support global health and evidence based public health.",2015 Jul 23,"Asokan, Govindaraj V.",Cent Asian J Glob Health,,,True
7461fe0adbb9a865f8a79e994c6cd8b8ebdd4e78,PMC,Would it be legally justified to impose vaccination in Israel? Examining the issue in light of the 2013 detection of polio in Israeli sewage,http://dx.doi.org/10.1186/s13584-017-0182-z,PMC5661933,29084599,CC BY,"BACKGROUND: The detection of wild poliovirus in Israeli sewage in May 2013 led the health authorities to decide that children who had been vaccinated with IPV would also be vaccinated with OPV. The decision sought to protect vulnerable Israeli individuals who were either not vaccinated with IPV or who suffered from an immune deficiency, to preserve Israel’s status as a polio-free country, to prevent the virus’ “exportation” into vulnerable polio-free countries, and to participate in the global efforts toward the eradication of polio. After a massive public persuasion campaign, 79% of the children born after 2004 were vaccinated as well as 69% of the children residing in central Israel. A 2014 State Comptroller Report stated that the Ministry of Health should draw conclusions from the low compliance rates in certain Israeli regions. GOALS: The article seeks to examine the legal legitimacy of mandatory vaccination in the service of eradicating a contagious disease (as opposed to preventing a pandemic outbreak), which was one of the objectives in the 2013 Polio case. It more specifically relates to current Israeli law as well as to a hypothetical new public health law which would authorize health officials to oblige vaccination and enforce this through the use of criminal sanctions. METHOD: Qualitative content analysis through the interpretation of court judgements, laws, legislative protocols, health ministry guidelines and documented discussions of the Advisory Committee on Infectious Diseases and Immunization. MAIN FINDINGS AND CONCLUSION: A mandatory vaccination backed by criminal sanctions in the service of the eradication of contagious diseases would probably be perceived as infringing on the constitutional right to autonomy to a greater extent than necessary according to Israeli law and case law precedents. There may be some added value inherent in a new public health law which would authorize health officials to oblige vaccination where nonrestrictive measures have been ineffective. However, the law should also specify a variety of sanctions to accompany the enforcement of mandatory vaccinations which would be formulated from least to most restrictive according to the “intervention ladder” concept. The law should also describe the circumstances which would justify the implementation of each and every sanction as well as the procedural safeguards designed for established decisions and fairness toward the individual(s) whose rights are infringed by the application of these sanctions.",2017 Oct 30,"Kamin-Friedman, Shelly",Isr J Health Policy Res,,,True
fa4d272c79931c9d40575defb54ac24b37869bc9,PMC,MultiBac: from protein complex structures to synthetic viral nanosystems,http://dx.doi.org/10.1186/s12915-017-0447-6,PMC5661938,29084535,CC BY,"The MultiBac baculovirus/insect cell expression vector system was conceived as a user-friendly, modular tool-kit for producing multiprotein complexes for structural biology applications. MultiBac has allowed the structure and function of many molecular machines to be elucidated, including previously inaccessible high-value drug targets. More recently, MultiBac developments have shifted to customized baculoviral genomes that are tailored for a range of applications, including synthesizing artificial proteins by genetic code expansion. We review some of these developments, including the ongoing rewiring of the MultiBac system for mammalian applications, notably CRISPR/Cas9-mediated gene editing.",2017 Oct 30,"['Pelosse, Martin', 'Crocker, Hannah', 'Gorda, Barbara', 'Lemaire, Paul', 'Rauch, Jens', 'Berger, Imre']",BMC Biol,,,True
a85684483483909019d84ebf3061582317fc841e,PMC,Virus-Vectored Ebola Vaccines,,PMC5662269,29104771,CC BY,"The Ebola virus disease (EVD) is one of the most dangerous infections affecting humans and animals. The first EVD outbreaks occurred in 1976 in Sudan and Zaire. Since then, more than 20 outbreaks have occurred; the largest of which (2014−2016) evolved into an epidemic in West Africa and claimed the lives of more than 11,000 people. Although vaccination is the most effective way to prevent epidemics, there was no licensed vaccine for EVD at the beginning of the latest outbreak. The development of the first vaccines for EVD started in 1980 and has come a long technological way, from inactivated to genetically engineered vaccines based on recombinant viral vectors. This review focuses on virus-vectored Ebola vaccines that have demonstrated the greatest efficacy in preclinical trials and are currently under different phases of clinical trial. Particular attention is paid to the mechanisms of immune response development, which are important for protection from EVD, and the key vaccine parameters necessary for inducing long-term protective immunity against EVD.",2017 Jul-Sep,"['Dolzhikova, I.V.', 'Tokarskaya, E.A.', 'Dzharullaeva, A. S.', 'Tukhvatulin, A. I.', 'Shcheblyakov, D. V.', 'Voronina, O.L.', 'Syromyatnikova, S. I.', 'Borisevich, S. V.', 'Pantyukhov, V. B.', 'Babira, V. F.', 'Kolobukhina, L. V.', 'Naroditsky, B. S.', 'Logunov, D. Y.', 'Gintsburg, A. L.']",Acta Naturae,,,True
dfa781bcc4c907490ddfceebd374669983a98082,PMC,The molecular epidemiology of respiratory viruses associated with asthma attacks: A single-center observational study in Japan,http://dx.doi.org/10.1097/MD.0000000000008204,PMC5662372,29049206,CC BY,"Few reports have described the significance of viral respiratory infections (VRIs) in exacerbation of asthma in adult patients. The aim of this study was to elucidate the profiles of VRIs in adult patients with asthma along with their molecular epidemiology. A cross-sectional observational study was conducted at Kyorin University Hospital from August 2012 to May 2015. To identify respiratory pathogens in inpatients and outpatients suffering from asthma attacks, RT-PCR/sequencing/phylogenetic analysis methods were applied alongside conventional microbiological methods. Phylogenetic and pairwise distance analyses of 10 viruses were performed. A total of 106 asthma attack patients enrolled in this study in both inpatient (n = 49) and outpatient (n = 57) settings. The total 106 respiratory samples were obtained from nasopharyngeal swab (n = 68) or sputum (n = 38). Among these, patients with virus alone (n = 39), virus and bacterial (n = 5), and bacterial alone (n = 5) were identified. The ratio of virus-positive patients in inpatient or outpatient to the total cases were 31.1% (n = 33) and 10.4% (n = 11), respectively. The frequency of virus-positive patients was significantly higher in inpatients (75.3%, n = 33) than in outpatients (19.3%, n = 11). Major VRIs included human rhinovirus (HRV) (n = 24), human metapneumovirus (hMPV) (n = 9), influenza virus (Inf-V) (n = 8), and respiratory syncytial virus (RSV) (n = 3) infections with seasonal variations. HRV-A and HRV-C were the most commonly detected viruses, with wide genetic divergence on phylogenetic analysis. Asthmatic exacerbations in adults are highly associated with VRIs such as HRV-A or HRV-C, hMPV, RSV, and Inf-V infections with seasonal variations and genetic divergence, but similar frequencies of VRIs occurred in asthma attack patients throughout the seasons.",2017 Oct 20,"['Saraya, Takeshi', 'Kimura, Hirokazu', 'Kurai, Daisuke', 'Ishii, Haruyuki', 'Takizawa, Hajime']",Medicine (Baltimore),,,True
c3d247dfd60d48b2dcbb5996371c80b01f99dd22,PMC,Comparing the protective performances of 3 types of N95 filtering facepiece respirators during chest compressions: A randomized simulation study,http://dx.doi.org/10.1097/MD.0000000000008308,PMC5662401,29049235,CC BY,"OBJECTIVE: Healthcare providers in emergency departments should wear respirators for infection protection. However, the wearer's vigorous movements during cardiopulmonary resuscitation may affect the protective performance of the respirator. Herein, we aimed to assess the effects of chest compressions (CCs) on the protective performance of respirators. METHODS: This crossover study evaluated 30 healthcare providers from 1 emergency department who performed CC with real-time feedback. The first, second, and third groups started with a cup-type, fold-type, and valve-type respirator, respectively, after which the respirators were randomized for each group. The fit factors were measured using a quantitative fit testing device before and during the CC in each experiment. The protection rate was defined as the proportion of respirators achieving a fit factor ≥100. RESULTS: The fold-type respirator had a significantly greater protection rate at baseline (100.0% ± 0.0%) compared to the cup-type (73.6% ± 39.6%, P = .003) and valve-type respirators (87.5% ± 30.3%, P = .012). During the CC, the fit factor values significantly decreased for the cup-type (44.9% ± 42.8%, P < .001) and valve-type respirators (59.5% ± 41.7%, P = .002), but not for the fold-type respirator (93.2% ± 21.7%, P = .095). CONCLUSIONS: The protective performances of respirators may be influenced by CC. Healthcare providers should identify the respirator that provides the best fit for their intended tasks.",2017 Oct 20,"['Shin, Hyungoo', 'Oh, Jaehoon', 'Lim, Tae Ho', 'Kang, Hyunggoo', 'Song, Yeongtak', 'Lee, Sanghyun']",Medicine (Baltimore),,,True
72a5995cb9dc08122a069c6b02e72f2894e0b07c,PMC,Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A Activation,http://dx.doi.org/10.1155/2017/4302320,PMC5662805,29124072,CC BY,"The epigenetic silencing of tumor suppressor genes in myelodysplastic syndromes (MDS) can potentially confer a growth advantage to individual cellular clones. Currently, the recommended treatment for patients with high-risk MDS is the methylation agent decitabine (DAC), a drug that can induce the reexpression of silenced tumor suppressor genes. We investigated the effects of DAC treatment on the myeloid MDS cell line SKM-1 and investigated the role of FOXO3A, a potentially tumor-suppressive transcription factor, by silencing its expression prior to DAC treatment. We found that FOXO3A exists in an inactive, hyperphosphorylated form in SKM-1 cells, but that DAC both induces FOXO3A expression and reactivates the protein by reducing its phosphorylation level. Furthermore, we show that this FOXO3A activation is responsible for the DAC-induced differentiation of SKM-1 cells into monocytes, as well as for SKM-1 cell cycle arrest, apoptosis, and autophagy. Collectively, these results suggest that FOXO3A reactivation may contribute to the therapeutic effects of DAC in MDS.",2017 Oct 16,"['Zeng, Wen', 'Dai, Hanjun', 'Yan, Ming', 'Cai, Xiaojun', 'Luo, Hong', 'Ke, Min', 'Liu, Zeming']",J Immunol Res,,,True
2757ce8aa9cfdd87202c39c244d8f8313f4a2ca3,PMC,DExD/H-Box Helicase 36 Signaling via Myeloid Differentiation Primary Response Gene 88 Contributes to NF-κB Activation to Type 2 Porcine Reproductive and Respiratory Syndrome Virus Infection,http://dx.doi.org/10.3389/fimmu.2017.01365,PMC5662876,29123520,CC BY,"DExD/H-box helicase 36 (DHX36) is known to be an ATP-dependent RNA helicase that unwinds the guanine-quadruplexes DNA or RNA, but emerging data suggest that it also functions as pattern recognition receptor in innate immunity. Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has been devastating the swine industry worldwide. Interstitial pneumonia is considered to be one of the most obvious clinical signs of PRRSV infection, suggesting that the inflammatory response plays an important role in PRRSV pathogenesis. However, whether DHX36 is involved in PRRSV-induced inflammatory cytokine expression remains unclear. In this study, we found that PRRSV infection increased the expression of DHX36. Knockdown of DHX36 and its adaptor myeloid differentiation primary response gene 88 (MyD88) by small-interfering RNA in MARC-145 cells significantly reduced NF-κB activation and pro-inflammatory cytokine expression after PRRSV infection. Further investigation revealed that PRRSV nucleocapsid protein interacted with the N-terminal quadruplex binding domain of DHX36, which in turn augmented nucleocapsid protein-induced NF-κB activation. Taken together, our results suggest that DHX36–MyD88 has a relevant role in the recognition of PRRSV nucleocapsid protein and in the subsequent activation of pro-inflammatory NF-κB pathway.",2017 Oct 23,"['Jing, Huiyuan', 'Zhou, Yanrong', 'Fang, Liurong', 'Ding, Zhen', 'Wang, Dang', 'Ke, Wenting', 'Chen, Huanchun', 'Xiao, Shaobo']",Front Immunol,,,True
5b1c0f67f5fbd0524136149e16313ffe0381fead,PMC,The Rho ADP-ribosylating C3 exoenzyme binds cells via an Arg–Gly–Asp motif,http://dx.doi.org/10.1074/jbc.M117.798231,PMC5663871,28882889,CC BY,"The Rho ADP-ribosylating C3 exoenzyme (C3bot) is a bacterial protein toxin devoid of a cell-binding or -translocation domain. Nevertheless, C3 can efficiently enter intact cells, including neurons, but the mechanism of C3 binding and uptake is not yet understood. Previously, we identified the intermediate filament vimentin as an extracellular membranous interaction partner of C3. However, uptake of C3 into cells still occurs (although reduced) in the absence of vimentin, indicating involvement of an additional host cell receptor. C3 harbors an Arg–Gly–Asp (RGD) motif, which is the major integrin-binding site, present in a variety of integrin ligands. To check whether the RGD motif of C3 is involved in binding to cells, we performed a competition assay with C3 and RGD peptide or with a monoclonal antibody binding to β1-integrin subunit and binding assays in different cell lines, primary neurons, and synaptosomes with C3-RGD mutants. Here, we report that preincubation of cells with the GRGDNP peptide strongly reduced C3 binding to cells. Moreover, mutation of the RGD motif reduced C3 binding to intact cells and also to recombinant vimentin. Anti-integrin antibodies also lowered the C3 binding to cells. Our results indicate that the RGD motif of C3 is at least one essential C3 motif for binding to host cells and that integrin is an additional receptor for C3 besides vimentin.",2017 Oct 27,"['Rohrbeck, Astrid', 'Höltje, Markus', 'Adolf, Andrej', 'Oms, Elisabeth', 'Hagemann, Sandra', 'Ahnert-Hilger, Gudrun', 'Just, Ingo']",J Biol Chem,,,False
e1be35b4c835e9b982fe494d2d0b6e3fb1622d2e,PMC,The Rho ADP-ribosylating C3 exoenzyme binds cells via an Arg–Gly–Asp motif,http://dx.doi.org/10.1074/jbc.M117.798231,PMC5663871,28882889,CC BY,"The Rho ADP-ribosylating C3 exoenzyme (C3bot) is a bacterial protein toxin devoid of a cell-binding or -translocation domain. Nevertheless, C3 can efficiently enter intact cells, including neurons, but the mechanism of C3 binding and uptake is not yet understood. Previously, we identified the intermediate filament vimentin as an extracellular membranous interaction partner of C3. However, uptake of C3 into cells still occurs (although reduced) in the absence of vimentin, indicating involvement of an additional host cell receptor. C3 harbors an Arg–Gly–Asp (RGD) motif, which is the major integrin-binding site, present in a variety of integrin ligands. To check whether the RGD motif of C3 is involved in binding to cells, we performed a competition assay with C3 and RGD peptide or with a monoclonal antibody binding to β1-integrin subunit and binding assays in different cell lines, primary neurons, and synaptosomes with C3-RGD mutants. Here, we report that preincubation of cells with the GRGDNP peptide strongly reduced C3 binding to cells. Moreover, mutation of the RGD motif reduced C3 binding to intact cells and also to recombinant vimentin. Anti-integrin antibodies also lowered the C3 binding to cells. Our results indicate that the RGD motif of C3 is at least one essential C3 motif for binding to host cells and that integrin is an additional receptor for C3 besides vimentin.",2017 Oct 27,"['Rohrbeck, Astrid', 'Höltje, Markus', 'Adolf, Andrej', 'Oms, Elisabeth', 'Hagemann, Sandra', 'Ahnert-Hilger, Gudrun', 'Just, Ingo']",J Biol Chem,,,True
7b7239eb6365a09200f504c503cf13887543ccd5,PMC,HLA-DMB restricts human T-cell leukemia virus type-1 (HTLV-1) protein expression via regulation of ATG7 acetylation,http://dx.doi.org/10.1038/s41598-017-14882-z,PMC5663917,29089548,CC BY,"The roles of autophagy in viral infection are complicated. While autophagy has been shown to function in host antiviral defense by eliminating intracellular viruses and regulating adaptive immunity, several viruses have evolved molecular mechanisms to get benefits from it. The deltaretrovirus human T-cell leukemia virus type-1 (HTLV-1) has been reported to profit its replication from enhancing autophagosome accumulation. Here, we reported that HLA-DMB (generally referred to here as DMB), the beta chain of the non-classical MHC-II protein HLA-DM, had strong expression in HTLV-1-transformed T-cell lines and could be induced in Hela, PMA-differentiated THP1 (PMA-THP1) or primary human monocytes by HTLV-1 infection. Immunoblot and real-time PCR assays demonstrated that overexpression of DMB decreased HTLV-1 protein expression while the knockdown of DMB increased HTLV-1 protein expression. Immunoblot and confocal microscopy assays indicated that overexpression of DMB decreased HTLV-1 induced autophagosome accumulation while the knockdown of DMB yielded the opposite effects. Coimmunoprecipitation and immunoprecipitation experiments suggested DMB interacted with autophagy-related gene (ATG) 7 and increased the acetylation of ATG7. Taken together, these results suggested DMB modulated HTLV-1 protein expression through regulation of autophagosome accumulation and our findings suggested a new mechanism by which the host cells defended against HTLV-1 infection.",2017 Oct 31,"['Wang, Jie', 'Song, Di', 'Liu, Yanzi', 'Lu, Guangjian', 'Yang, Shuai', 'Liu, Lu', 'Gao, Zhitao', 'Ma, Lingling', 'Guo, Zhixiang', 'Zhang, Chenguang', 'Wang, Hui', 'Yang, Bo']",Sci Rep,,,False
4aa092956fea94f9487d129b4a05a8704b73d0fc,PMC,HLA-DMB restricts human T-cell leukemia virus type-1 (HTLV-1) protein expression via regulation of ATG7 acetylation,http://dx.doi.org/10.1038/s41598-017-14882-z,PMC5663917,29089548,CC BY,"The roles of autophagy in viral infection are complicated. While autophagy has been shown to function in host antiviral defense by eliminating intracellular viruses and regulating adaptive immunity, several viruses have evolved molecular mechanisms to get benefits from it. The deltaretrovirus human T-cell leukemia virus type-1 (HTLV-1) has been reported to profit its replication from enhancing autophagosome accumulation. Here, we reported that HLA-DMB (generally referred to here as DMB), the beta chain of the non-classical MHC-II protein HLA-DM, had strong expression in HTLV-1-transformed T-cell lines and could be induced in Hela, PMA-differentiated THP1 (PMA-THP1) or primary human monocytes by HTLV-1 infection. Immunoblot and real-time PCR assays demonstrated that overexpression of DMB decreased HTLV-1 protein expression while the knockdown of DMB increased HTLV-1 protein expression. Immunoblot and confocal microscopy assays indicated that overexpression of DMB decreased HTLV-1 induced autophagosome accumulation while the knockdown of DMB yielded the opposite effects. Coimmunoprecipitation and immunoprecipitation experiments suggested DMB interacted with autophagy-related gene (ATG) 7 and increased the acetylation of ATG7. Taken together, these results suggested DMB modulated HTLV-1 protein expression through regulation of autophagosome accumulation and our findings suggested a new mechanism by which the host cells defended against HTLV-1 infection.",2017 Oct 31,"['Wang, Jie', 'Song, Di', 'Liu, Yanzi', 'Lu, Guangjian', 'Yang, Shuai', 'Liu, Lu', 'Gao, Zhitao', 'Ma, Lingling', 'Guo, Zhixiang', 'Zhang, Chenguang', 'Wang, Hui', 'Yang, Bo']",Sci Rep,,,True
b8e9c45dda9cb8c9c4321a55704ab2a66fb34f7d,PMC,Diagnostic Accuracy of FebriDx: A Rapid Test to Detect Immune Responses to Viral and Bacterial Upper Respiratory Infections,http://dx.doi.org/10.3390/jcm6100094,PMC5664009,28991170,CC BY,"C-reactive protein (CRP) and myxovirus resistance protein A (MxA) are associated with bacterial and viral infections, respectively. We conducted a prospective, multicenter, cross-sectional study of adults and children with febrile upper respiratory tract infections (URIs) to evaluate the diagnostic accuracy of a rapid CRP/MxA immunoassay to identify clinically significant bacterial infection with host response and acute pathogenic viral infection. The reference standard for classifying URI etiology was an algorithm that included throat bacterial culture, upper respiratory PCR for viral and atypical pathogens, procalcitonin, white blood cell count, and bandemia. The algorithm also allowed for physician override. Among 205 patients, 25 (12.2%) were classified as bacterial, 53 (25.9%) as viral, and 127 (62.0%) negative by the reference standard. For bacterial detection, agreement between FebriDx and the reference standard was 91.7%, with FebriDx having a sensitivity of 80% (95% CI: 59–93%), specificity of 93% (89–97%), positive predictive value (PPV) of 63% (45–79%), and a negative predictive value (NPV) of 97% (94–99%). For viral detection, agreement was 84%, with a sensitivity of 87% (75–95%), specificity of 83% (76–89%), PPV of 64% (63–75%), and NPV of 95% (90–98%). FebriDx may help to identify clinically significant immune responses associated with bacterial and viral URIs that are more likely to require clinical management or therapeutic intervention, and has potential to assist with antibiotic stewardship.",2017 Oct 7,"['Self, Wesley H.', 'Rosen, Jeffrey', 'Sharp, Stephan C.', 'Filbin, Michael R.', 'Hou, Peter C.', 'Parekh, Amisha D.', 'Kurz, Michael C.', 'Shapiro, Nathan I.']",J Clin Med,,,True
5a7988cd92e05a8bca504b5f1a467e2c8d3976d2,PMC,"Analysis of Transmission and Control of Tuberculosis in Mainland China, 2005–2016, Based on the Age-Structure Mathematical Model",http://dx.doi.org/10.3390/ijerph14101192,PMC5664693,28991169,CC BY,"Tuberculosis (TB), an air-borne infectious disease, is a major public-health problem in China. The reported number of the active tuberculosis cases is about one million each year. The morbidity data for 2005–2012 reflect that the difference in morbidity based on age group is significant, thus the role of age-structure on the transmission of TB needs to be further developed. In this work, based on the reported data and the observed morbidity characteristics, we propose a susceptible-exposed-infectious-recovered (SEIR) epidemic model with age groupings, involving three categories: children, the middle-aged, and senior to investigate the role of age on the transmission of tuberculosis in Mainland China from 2005 to 2016. Then, we evaluated the parameters by the Least Square method and simulated the model and it had good alignment with the reported infected TB data in Mainland China. Furthermore, we estimated the basic reproduction number [Formula: see text] of [Formula: see text] , with an obtained 95% confidence interval for [Formula: see text] of [Formula: see text] by Latin hypercube sampling, and we completed a sensitivity analysis of [Formula: see text] in terms of some parameters. Our study demonstrates that diverse age groups have different effects on TB. Two effective measures were found that would help reach the goals of the World Health Organization (WHO) End TB Strategy: an increase in the recovery rate and the reduction in the infectious rate of the senior age group.",2017 Oct 7,"['Zhao, Yu', 'Li, Mingtao', 'Yuan, Sanling']",Int J Environ Res Public Health,,,True
b0cf5fb3ba91c15b0f93c584949fbc235f5b2d1a,PMC,"Abundance, survival, recruitment and effectiveness of sterilization of free-roaming dogs: A capture and recapture study in Brazil",http://dx.doi.org/10.1371/journal.pone.0187233,PMC5665538,29091961,CC BY,"The existence of free-roaming dogs raises important issues in animal welfare and in public health. A proper understanding of these animals’ ecology is useful as a necessary input to plan strategies to control these populations. The present study addresses the population dynamics and the effectiveness of the sterilization of unrestricted dogs using capture and recapture procedures suitable for open animal populations. Every two months, over a period of 14 months, we captured, tagged, released and recaptured dogs in two regions in a city in the southeast region of Brazil. In one of these regions the animals were also sterilized. Both regions had similar social, environmental and demographic features. We estimated the presence of 148 females and 227 males during the period of study. The average dog:man ratio was 1 dog for each 42 and 51 human beings, in the areas without and with sterilization, respectively. The animal population size increased in both regions, due mainly to the abandonment of domestic dogs. Mortality rate decreased throughout the study period. Survival probabilities did not differ between genders, but males entered the population in higher numbers. There were no differences in abundance, survival and recruitment between the regions, indicating that sterilization did not affect the population dynamics. Our findings indicate that the observed animal dynamics were influenced by density-independent factors, and that sterilization might not be a viable and effective strategy in regions where availability of resources is low and animal abandonment rates are high. Furthermore, the high demographic turnover rates observed render the canine free-roaming population younger, thus more susceptible to diseases, especially to rabies and leishmaniasis. We conclude by stressing the importance of implementing educational programs to promote responsible animal ownership and effective strategies against abandonment practices.",2017 Nov 1,"['Belo, Vinícius Silva', 'Struchiner, Claudio José', 'Werneck, Guilherme Loureiro', 'Teixeira Neto, Rafael Gonçalves', 'Tonelli, Gabriel Barbosa', 'de Carvalho Júnior, Clóvis Gomes', 'Ribeiro, Renata Aparecida Nascimento', 'da Silva, Eduardo Sérgio']",PLoS One,,,True
02c03ab3643bdcfd6986d10d268114ac83a19d6b,PMC,"Abundance, survival, recruitment and effectiveness of sterilization of free-roaming dogs: A capture and recapture study in Brazil",http://dx.doi.org/10.1371/journal.pone.0187233,PMC5665538,29091961,CC BY,"The existence of free-roaming dogs raises important issues in animal welfare and in public health. A proper understanding of these animals’ ecology is useful as a necessary input to plan strategies to control these populations. The present study addresses the population dynamics and the effectiveness of the sterilization of unrestricted dogs using capture and recapture procedures suitable for open animal populations. Every two months, over a period of 14 months, we captured, tagged, released and recaptured dogs in two regions in a city in the southeast region of Brazil. In one of these regions the animals were also sterilized. Both regions had similar social, environmental and demographic features. We estimated the presence of 148 females and 227 males during the period of study. The average dog:man ratio was 1 dog for each 42 and 51 human beings, in the areas without and with sterilization, respectively. The animal population size increased in both regions, due mainly to the abandonment of domestic dogs. Mortality rate decreased throughout the study period. Survival probabilities did not differ between genders, but males entered the population in higher numbers. There were no differences in abundance, survival and recruitment between the regions, indicating that sterilization did not affect the population dynamics. Our findings indicate that the observed animal dynamics were influenced by density-independent factors, and that sterilization might not be a viable and effective strategy in regions where availability of resources is low and animal abandonment rates are high. Furthermore, the high demographic turnover rates observed render the canine free-roaming population younger, thus more susceptible to diseases, especially to rabies and leishmaniasis. We conclude by stressing the importance of implementing educational programs to promote responsible animal ownership and effective strategies against abandonment practices.",2017 Nov 1,"['Belo, Vinícius Silva', 'Struchiner, Claudio José', 'Werneck, Guilherme Loureiro', 'Teixeira Neto, Rafael Gonçalves', 'Tonelli, Gabriel Barbosa', 'de Carvalho Júnior, Clóvis Gomes', 'Ribeiro, Renata Aparecida Nascimento', 'da Silva, Eduardo Sérgio']",PLoS One,,,False
6ae0d0044c9b5e4f19ba8b1273afbd1a6b06f192,PMC,"Abundance, survival, recruitment and effectiveness of sterilization of free-roaming dogs: A capture and recapture study in Brazil",http://dx.doi.org/10.1371/journal.pone.0187233,PMC5665538,29091961,CC BY,"The existence of free-roaming dogs raises important issues in animal welfare and in public health. A proper understanding of these animals’ ecology is useful as a necessary input to plan strategies to control these populations. The present study addresses the population dynamics and the effectiveness of the sterilization of unrestricted dogs using capture and recapture procedures suitable for open animal populations. Every two months, over a period of 14 months, we captured, tagged, released and recaptured dogs in two regions in a city in the southeast region of Brazil. In one of these regions the animals were also sterilized. Both regions had similar social, environmental and demographic features. We estimated the presence of 148 females and 227 males during the period of study. The average dog:man ratio was 1 dog for each 42 and 51 human beings, in the areas without and with sterilization, respectively. The animal population size increased in both regions, due mainly to the abandonment of domestic dogs. Mortality rate decreased throughout the study period. Survival probabilities did not differ between genders, but males entered the population in higher numbers. There were no differences in abundance, survival and recruitment between the regions, indicating that sterilization did not affect the population dynamics. Our findings indicate that the observed animal dynamics were influenced by density-independent factors, and that sterilization might not be a viable and effective strategy in regions where availability of resources is low and animal abandonment rates are high. Furthermore, the high demographic turnover rates observed render the canine free-roaming population younger, thus more susceptible to diseases, especially to rabies and leishmaniasis. We conclude by stressing the importance of implementing educational programs to promote responsible animal ownership and effective strategies against abandonment practices.",2017 Nov 1,"['Belo, Vinícius Silva', 'Struchiner, Claudio José', 'Werneck, Guilherme Loureiro', 'Teixeira Neto, Rafael Gonçalves', 'Tonelli, Gabriel Barbosa', 'de Carvalho Júnior, Clóvis Gomes', 'Ribeiro, Renata Aparecida Nascimento', 'da Silva, Eduardo Sérgio']",PLoS One,,,False
7670874c4f3be682f68bde5ef70c2e7ca64070e9,PMC,"Abundance, survival, recruitment and effectiveness of sterilization of free-roaming dogs: A capture and recapture study in Brazil",http://dx.doi.org/10.1371/journal.pone.0187233,PMC5665538,29091961,CC BY,"The existence of free-roaming dogs raises important issues in animal welfare and in public health. A proper understanding of these animals’ ecology is useful as a necessary input to plan strategies to control these populations. The present study addresses the population dynamics and the effectiveness of the sterilization of unrestricted dogs using capture and recapture procedures suitable for open animal populations. Every two months, over a period of 14 months, we captured, tagged, released and recaptured dogs in two regions in a city in the southeast region of Brazil. In one of these regions the animals were also sterilized. Both regions had similar social, environmental and demographic features. We estimated the presence of 148 females and 227 males during the period of study. The average dog:man ratio was 1 dog for each 42 and 51 human beings, in the areas without and with sterilization, respectively. The animal population size increased in both regions, due mainly to the abandonment of domestic dogs. Mortality rate decreased throughout the study period. Survival probabilities did not differ between genders, but males entered the population in higher numbers. There were no differences in abundance, survival and recruitment between the regions, indicating that sterilization did not affect the population dynamics. Our findings indicate that the observed animal dynamics were influenced by density-independent factors, and that sterilization might not be a viable and effective strategy in regions where availability of resources is low and animal abandonment rates are high. Furthermore, the high demographic turnover rates observed render the canine free-roaming population younger, thus more susceptible to diseases, especially to rabies and leishmaniasis. We conclude by stressing the importance of implementing educational programs to promote responsible animal ownership and effective strategies against abandonment practices.",2017 Nov 1,"['Belo, Vinícius Silva', 'Struchiner, Claudio José', 'Werneck, Guilherme Loureiro', 'Teixeira Neto, Rafael Gonçalves', 'Tonelli, Gabriel Barbosa', 'de Carvalho Júnior, Clóvis Gomes', 'Ribeiro, Renata Aparecida Nascimento', 'da Silva, Eduardo Sérgio']",PLoS One,,,False
6f431652ac691a39f51b36a1383c88c51bc6c3e9,PMC,"Abundance, survival, recruitment and effectiveness of sterilization of free-roaming dogs: A capture and recapture study in Brazil",http://dx.doi.org/10.1371/journal.pone.0187233,PMC5665538,29091961,CC BY,"The existence of free-roaming dogs raises important issues in animal welfare and in public health. A proper understanding of these animals’ ecology is useful as a necessary input to plan strategies to control these populations. The present study addresses the population dynamics and the effectiveness of the sterilization of unrestricted dogs using capture and recapture procedures suitable for open animal populations. Every two months, over a period of 14 months, we captured, tagged, released and recaptured dogs in two regions in a city in the southeast region of Brazil. In one of these regions the animals were also sterilized. Both regions had similar social, environmental and demographic features. We estimated the presence of 148 females and 227 males during the period of study. The average dog:man ratio was 1 dog for each 42 and 51 human beings, in the areas without and with sterilization, respectively. The animal population size increased in both regions, due mainly to the abandonment of domestic dogs. Mortality rate decreased throughout the study period. Survival probabilities did not differ between genders, but males entered the population in higher numbers. There were no differences in abundance, survival and recruitment between the regions, indicating that sterilization did not affect the population dynamics. Our findings indicate that the observed animal dynamics were influenced by density-independent factors, and that sterilization might not be a viable and effective strategy in regions where availability of resources is low and animal abandonment rates are high. Furthermore, the high demographic turnover rates observed render the canine free-roaming population younger, thus more susceptible to diseases, especially to rabies and leishmaniasis. We conclude by stressing the importance of implementing educational programs to promote responsible animal ownership and effective strategies against abandonment practices.",2017 Nov 1,"['Belo, Vinícius Silva', 'Struchiner, Claudio José', 'Werneck, Guilherme Loureiro', 'Teixeira Neto, Rafael Gonçalves', 'Tonelli, Gabriel Barbosa', 'de Carvalho Júnior, Clóvis Gomes', 'Ribeiro, Renata Aparecida Nascimento', 'da Silva, Eduardo Sérgio']",PLoS One,,,False
fdbf58a578b97feac69f4156e932c1b48f036ef4,PMC,"Abundance, survival, recruitment and effectiveness of sterilization of free-roaming dogs: A capture and recapture study in Brazil",http://dx.doi.org/10.1371/journal.pone.0187233,PMC5665538,29091961,CC BY,"The existence of free-roaming dogs raises important issues in animal welfare and in public health. A proper understanding of these animals’ ecology is useful as a necessary input to plan strategies to control these populations. The present study addresses the population dynamics and the effectiveness of the sterilization of unrestricted dogs using capture and recapture procedures suitable for open animal populations. Every two months, over a period of 14 months, we captured, tagged, released and recaptured dogs in two regions in a city in the southeast region of Brazil. In one of these regions the animals were also sterilized. Both regions had similar social, environmental and demographic features. We estimated the presence of 148 females and 227 males during the period of study. The average dog:man ratio was 1 dog for each 42 and 51 human beings, in the areas without and with sterilization, respectively. The animal population size increased in both regions, due mainly to the abandonment of domestic dogs. Mortality rate decreased throughout the study period. Survival probabilities did not differ between genders, but males entered the population in higher numbers. There were no differences in abundance, survival and recruitment between the regions, indicating that sterilization did not affect the population dynamics. Our findings indicate that the observed animal dynamics were influenced by density-independent factors, and that sterilization might not be a viable and effective strategy in regions where availability of resources is low and animal abandonment rates are high. Furthermore, the high demographic turnover rates observed render the canine free-roaming population younger, thus more susceptible to diseases, especially to rabies and leishmaniasis. We conclude by stressing the importance of implementing educational programs to promote responsible animal ownership and effective strategies against abandonment practices.",2017 Nov 1,"['Belo, Vinícius Silva', 'Struchiner, Claudio José', 'Werneck, Guilherme Loureiro', 'Teixeira Neto, Rafael Gonçalves', 'Tonelli, Gabriel Barbosa', 'de Carvalho Júnior, Clóvis Gomes', 'Ribeiro, Renata Aparecida Nascimento', 'da Silva, Eduardo Sérgio']",PLoS One,,,False
bed1c9834dbd81a9e254940379f80c3447a122e9,PMC,Predicting virus emergence amid evolutionary noise,http://dx.doi.org/10.1098/rsob.170189,PMC5666085,29070612,CC BY,"The study of virus disease emergence, whether it can be predicted and how it might be prevented, has become a major research topic in biomedicine. Here we show that efforts to predict disease emergence commonly conflate fundamentally different evolutionary and epidemiological time scales, and are likely to fail because of the enormous number of unsampled viruses that could conceivably emerge in humans. Although we know much about the patterns and processes of virus evolution on evolutionary time scales as depicted in family-scale phylogenetic trees, these data have little predictive power to reveal the short-term microevolutionary processes that underpin cross-species transmission and emergence. Truly understanding disease emergence therefore requires a new mechanistic and integrated view of the factors that allow or prevent viruses spreading in novel hosts. We present such a view, suggesting that both ecological and genetic aspects of virus emergence can be placed within a simple population genetic framework, which in turn highlights the importance of host population size and density in determining whether emergence will be successful. Despite this framework, we conclude that a more practical solution to preventing and containing the successful emergence of new diseases entails ongoing virological surveillance at the human–animal interface and regions of ecological disturbance.",2017 Oct 25,"['Geoghegan, Jemma L.', 'Holmes, Edward C.']",Open Biol,,,True
bd57ac5cebeff6091e3ca6756a1efcf1c692b0f3,PMC,Infectious Bronchitis Virus Variants: Molecular Analysis and Pathogenicity Investigation,http://dx.doi.org/10.3390/ijms18102030,PMC5666712,28937583,CC BY,"Infectious bronchitis virus (IBV) variants constantly emerge and pose economic threats to poultry farms worldwide. Numerous studies on the molecular and pathogenic characterization of IBV variants have been performed between 2007 and 2017, which we have reviewed herein. We noted that viral genetic mutations and recombination events commonly gave rise to distinct IBV genotypes, serotypes and pathotypes. In addition to characterizing the S1 genes, full viral genomic sequencing, comprehensive antigenicity, and pathogenicity studies on emerging variants have advanced our understanding of IBV infections, which is valuable for developing countermeasures against IBV field outbreaks. This review of IBV variants provides practical value for understanding their phylogenetic relationships and epidemiology from both regional and worldwide viewpoints.",2017 Sep 22,"['Lin, Shu-Yi', 'Chen, Hui-Wen']",Int J Mol Sci,,,True
388dd96edecccdb339ea3626e0c31a6cea8c63cf,PMC,Infectious Bronchitis Virus Variants: Molecular Analysis and Pathogenicity Investigation,http://dx.doi.org/10.3390/ijms18102030,PMC5666712,28937583,CC BY,"Infectious bronchitis virus (IBV) variants constantly emerge and pose economic threats to poultry farms worldwide. Numerous studies on the molecular and pathogenic characterization of IBV variants have been performed between 2007 and 2017, which we have reviewed herein. We noted that viral genetic mutations and recombination events commonly gave rise to distinct IBV genotypes, serotypes and pathotypes. In addition to characterizing the S1 genes, full viral genomic sequencing, comprehensive antigenicity, and pathogenicity studies on emerging variants have advanced our understanding of IBV infections, which is valuable for developing countermeasures against IBV field outbreaks. This review of IBV variants provides practical value for understanding their phylogenetic relationships and epidemiology from both regional and worldwide viewpoints.",2017 Sep 22,"['Lin, Shu-Yi', 'Chen, Hui-Wen']",Int J Mol Sci,,,False
98451e334c51db917c85e62573eabd5bfaeac9e9,PMC,Biomarkers for Chronic Kidney Disease Associated with High Salt Intake,http://dx.doi.org/10.3390/ijms18102080,PMC5666762,28973979,CC BY,"High salt intake has been related to the development to chronic kidney disease (CKD) as well as hypertension. In its early stages, symptoms of CKD are usually not apparent, especially those that are induced in a “silent” manner in normotensive individuals, thereby providing a need for some kind of urinary biomarker to detect injury at an early stage. Because traditional renal biomarkers such as serum creatinine are insensitive, it is difficult to detect kidney injury induced by a high-salt diet, especially in normotensive individuals. Recently, several new biomarkers for damage of renal tubular epithelia such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) have been identified. Previously, we found a novel renal biomarker, urinary vanin-1, in several animal models with renal tubular injury. However, there are few studies about early biomarkers of the progression to CKD associated with a high-salt diet. This review presents some new insights about these novel biomarkers for CKD in normotensives and hypertensives under a high salt intake. Interestingly, our recent reports using spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) fed a high-salt diet revealed that urinary vanin-1 and NGAL are earlier biomarkers of renal tubular damage in SHR and WKY, whereas urinary Kim-1 is only useful as a biomarker of salt-induced renal injury in SHR. Clinical studies will be needed to clarify these findings.",2017 Sep 30,"Hosohata, Keiko",Int J Mol Sci,,,True
b1f385c02a27a04b941f53de42b53c1ecc1a7c94,PMC,Molecular Evolution of MERS Coronavirus: Dromedaries as a Recent Intermediate Host or Long-Time Animal Reservoir?,http://dx.doi.org/10.3390/ijms18102138,PMC5666820,29035289,CC BY,"While dromedary camels are the immediate animal source of MERS coronavirus (MERS-CoV) infection, the evolutionary origin of MERS-CoV remains obscure. We analyzed 219 camel and human MERS-CoV genome sequences available in GenBank. Phylogenetic analysis showed that 5 and 214 strains belong to clade A and B, respectively, with clade A further divided into lineage A1 (3 human strains) and lineage A2 (2 camel strains), and clade B divided into B1 to B6 (each containing both human and camel strains). Recombination analysis showed potential recombination events in five strains from dromedaries in Saudi Arabia, with recombination between lineage B5 and B3 in four strains, and between lineage B3 and B4 in one strain. The spike protein showed the highest number of amino acid substitutions, especially between A2 and other lineages, and contained positively selected codons. Notably, codon 1020 was positively selected among B and B5 strains, and can distinguish between clade A (Q1020) and B (R1020/H1020) strains, suggesting that this residue may play a role in the evolution of S protein during divergence of different lineages. The time of the most recent common ancestor of all MERS-CoV was dated to approximately 2010. The implications on the role of camels in the evolution of MERS-CoV are discussed.",2017 Oct 16,"['Lau, Susanna K. P.', 'Wong, Antonio C. P.', 'Lau, Terrence C. K.', 'Woo, Patrick C. Y.']",Int J Mol Sci,,,True
a0acb3cda6288d12ce50136a88c013a3098ee3fd,PMC,Characterizing the rapid spread of porcine epidemic diarrhea virus (PEDV) through an animal food manufacturing facility,http://dx.doi.org/10.1371/journal.pone.0187309,PMC5667810,29095859,CC BY,"New regulatory and consumer demands highlight the importance of animal feed as a part of our national food safety system. Porcine epidemic diarrhea virus (PEDV) is the first viral pathogen confirmed to be widely transmissible in animal food. Because the potential for viral contamination in animal food is not well characterized, the objectives of this study were to 1) observe the magnitude of virus contamination in an animal food manufacturing facility, and 2) investigate a proposed method, feed sequencing, to decrease virus decontamination on animal food-contact surfaces. A U.S. virulent PEDV isolate was used to inoculate 50 kg swine feed, which was mixed, conveyed, and discharged into bags using pilot-scale feed manufacturing equipment. Surfaces were swabbed and analyzed for the presence of PEDV RNA by quantitative real-time polymerase chain reaction (qPCR). Environmental swabs indicated complete contamination of animal food-contact surfaces (0/40 vs. 48/48, positive baseline samples/total baseline samples, positive subsequent samples/total subsequent samples, respectively; P < 0.05) and near complete contamination of non-animal food-contact surfaces (0/24 vs. 16/18, positive baseline samples/total baseline samples, positive subsequent samples/total subsequent samples, respectively; P < 0.05). Flushing animal food-contact surfaces with low-risk feed is commonly used to reduce cross-contamination in animal feed manufacturing. Thus, four subsequent 50 kg batches of virus-free swine feed were manufactured using the same system to test its impact on decontaminating animal food-contact surfaces. Even after 4 subsequent sequences, animal food-contact surfaces retained viral RNA (28/33 positive samples/total samples), with conveying system being more contaminated than the mixer. A bioassay to test infectivity of dust from animal food-contact surfaces failed to produce infectivity. This study demonstrates the potential widespread viral contamination of surfaces in an animal food manufacturing facility and the difficulty of removing contamination using conventional feed sequencing, which underscores the importance for preventing viruses from entering and contaminating such facilities.",2017 Nov 2,"['Schumacher, Loni L.', 'Huss, Anne R.', 'Cochrane, Roger A.', 'Stark, Charles R.', 'Woodworth, Jason C.', 'Bai, Jianfa', 'Poulsen, Elizabeth G.', 'Chen, Qi', 'Main, Rodger G.', 'Zhang, Jianqiang', 'Gauger, Phillip C.', 'Ramirez, Alejandro', 'Derscheid, Rachel J.', 'Magstadt, Drew M.', 'Dritz, Steve S.', 'Jones, Cassandra K.']",PLoS One,,,True
69003af6f71b1554fa58853d5d29d1dffd9afc24,PMC,Construction and characterization of an improved DNA-launched infectious clone of duck hepatitis a virus type 1,http://dx.doi.org/10.1186/s12985-017-0883-5,PMC5670519,29100535,CC BY,"BACKGROUND: DNA-launched infectious system is a useful tool with high rescue efficiency that allows the introduction of mutations in specific positions to investigate the function of an individual viral element. Rescued virus particles could be harvested by directly transfecting the DNA-launched recombinant plasmid to the host cells, which will reduce labor and experimental cost by skipping the in vitro transcription assay. METHODS: A total of four overlapping fragments covering the entire viral genome were amplified and then were assembled into a transformation vector based on pIRES2-EGFP to establish the DNA-launched infectious system of duck hepatitis A virus type 1 (DHAV-1), named pIR-DHAV-1. Reverse transcription polymerase chain reaction (RT-PCR) detection, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting assay and indirect immunofluorescence (IFA) were conducted for rescued virus identification. A total of 4.0 μg of recombinant plasmid of pIR-DHAV-1 and in vitro transcribed product of 4.0 μg of RNA-launched infectious clone named pR-DHAV-1 were transfected into BHK-21 cells to analyze the rescue efficiency. Following that, tissue tropism of rescued virus (rDHAV-1) and parental virus (pDHAV-1) were assayed for virulence testing in 1-day-old ducklings. RESULTS: Rescued virus particles carry the designed genetic marker which could be harvested by directly transfecting pIR-DHAV-1 to BHK-21 cells. The qRT-PCR and western blotting results indicated that rDHAV-1 shared similar growth characteristics with pDHAV-1. Furthermore, DNA-launched infectious system possessed much higher rescue efficiency assay compared to RNA-launched infectious system. The mutation at position 3042 from T to C has no impact on viral replication and tissue tropism. From 1 h post infection (hpi) to 48 hpi, the viral RNA copies of rDHAV-1 in liver were the highest among the six tested tissues (with an exception of thymus at 6 hpi), while the viral RNA copy numbers in heart and kidney were alternately the lowest. CONCLUSION: We have constructed a genetically stable and highly pathogenic DNA-launched infectious clone, from which the rescued virus could be harvested by direct transfection with recombinant plasmids. rDHAV-1 shared similar growth characteristics and tissue tropism with pDHAV-1. The DNA-launched infectious system of DHAV-1 possessed higher rescue efficiency compared to the traditional RNA-launched infectious system.",2017 Nov 3,"['Chen, Junhao', 'Zhang, Ruihua', 'Lin, Shaoli', 'Li, Pengfei', 'Lan, Jingjing', 'Xie, Zhijing', 'Wang, Yu', 'Jiang, Shijin']",Virol J,,,True
2e8bc0044aba50cc5c208dbab92d35493e05eb74,PMC,Investigation of antiviral state mediated by interferon-inducible transmembrane protein 1 induced by H9N2 virus and inactivated viral particle in human endothelial cells,http://dx.doi.org/10.1186/s12985-017-0875-5,PMC5670731,29100522,CC BY,"BACKGROUND: Endothelial cells are believed to play an important role in response to virus infection. Our previous microarray analysis showed that H9N2 virus infection and inactivated viral particle inoculation increased the expression of interferon-inducible transmembrane protein 1 (IFITM1) in human umbilical vein endothelial cells (HUVECs). In present study, we deeply investigated the expression patterns of IFITM1 and IFITM1-mediated antiviral response induced by H9N2 virus infection and inactivated viral particle inoculation in HUVECs. Epithelial cells that are considered target cells of the influenza virus were selected as a reference control. METHODS: First, we quantified the expression levels of IFITM1 in HUVECs induced by H9N2 virus infection or viral particle inoculation using quantitative real-time PCR and western blot. Second, we observed whether hemagglutinin or neuraminidase affected IFITM1 expression in HUVECs. Finally, we investigated the effect of induced-IFITM1 on the antiviral state in HUVECs by siRNA and activation plasmid transfection. RESULTS: Both H9N2 virus infection and viral particle inoculation increased the expression of IFITM1 without elevating the levels of interferon-ɑ/β in HUVECs. HA or NA protein binding alone is not sufficient to increase the levels of IFITM1 and interferon-ɑ/β in HUVECs. IFITM1 induced by viral particle inoculation significantly decreased the virus titers in culture supernatants of HUVECs. CONCLUSIONS: Our results showed that inactivated viral particle inoculation increased the expression of IFITM1 at mRNA and protein levels. Moreover, the induction of IFITM1 expression mediated the antiviral state in HUVECs.",2017 Nov 3,"['Feng, Bo', 'Zhao, Lihong', 'Wang, Wei', 'Wang, Jianfang', 'Wang, Hongyan', 'Duan, Huiqin', 'Zhang, Jianjun', 'Qiao, Jian']",Virol J,,,True
2c9a3072e8533ac8c5a74abfc595966d516a7878,PMC,Do Viruses Exchange Genes across Superkingdoms of Life?,http://dx.doi.org/10.3389/fmicb.2017.02110,PMC5671483,29163404,CC BY,"Viruses can be classified into archaeoviruses, bacterioviruses, and eukaryoviruses according to the taxonomy of the infected host. The host-constrained perception of viruses implies preference of genetic exchange between viruses and cellular organisms of their host superkingdoms and viral origins from host cells either via escape or reduction. However, viruses frequently establish non-lytic interactions with organisms and endogenize into the genomes of bacterial endosymbionts that reside in eukaryotic cells. Such interactions create opportunities for genetic exchange between viruses and organisms of non-host superkingdoms. Here, we take an atypical approach to revisit virus-cell interactions by first identifying protein fold structures in the proteomes of archaeoviruses, bacterioviruses, and eukaryoviruses and second by tracing their spread in the proteomes of superkingdoms Archaea, Bacteria, and Eukarya. The exercise quantified protein structural homologies between viruses and organisms of their host and non-host superkingdoms and revealed likely candidates for virus-to-cell and cell-to-virus gene transfers. Unexpected lifestyle-driven genetic affiliations between bacterioviruses and Eukarya and eukaryoviruses and Bacteria were also predicted in addition to a large cohort of protein folds that were universally shared by viral and cellular proteomes and virus-specific protein folds not detected in cellular proteomes. These protein folds provide unique insights into viral origins and evolution that are generally difficult to recover with traditional sequence alignment-dependent evolutionary analyses owing to the fast mutation rates of viral gene sequences.",2017 Oct 31,"['Malik, Shahana S.', 'Azem-e-Zahra, Syeda', 'Kim, Kyung Mo', 'Caetano-Anollés, Gustavo', 'Nasir, Arshan']",Front Microbiol,,,True
06485dd45c17460af629f7c74234bef914fbbabe,PMC,"Activation and Role of NACHT, LRR, and PYD Domains-Containing Protein 3 Inflammasome in RNA Viral Infection",http://dx.doi.org/10.3389/fimmu.2017.01420,PMC5671583,29163496,CC BY,"NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome activation and effects during ribonucleic acid (RNA) viral infection are the focus of a wide range of research currently. Both the pathogen-associated molecule pattern derived from virions and intracellular stress molecules involved in the process of viral infection lead to activation of the NLRP3 inflammasome, which in turn triggers inflammatory responses for antiviral defense and tissue healing. However, aberrant activation of the NLRP3 inflammasome can instead support viral pathogenesis and promote disease progression. Here, we summarize and expound upon the recent literature describing the molecular mechanisms underlying the activation and effects of the NLRP3 inflammasome in RNA viral infection to highlight how it provides protection against RNA viral infection.",2017 Oct 31,"['Yu, Junyang', 'Wu, Yuzhang', 'Wang, Jingxue']",Front Immunol,,,True
8590276b817018ff7fea07592055689f3d325d3a,PMC,Transmissible Gastroenteritis Virus Papain-Like Protease 1 Antagonizes Production of Interferon-β through Its Deubiquitinase Activity,http://dx.doi.org/10.1155/2017/7089091,PMC5672592,29201911,CC BY,"Coronaviruses (CoVs), such as human coronavirus NL63 (HCoV-NL63), severe acute respiratory syndrome CoV (SARS-CoV), murine hepatitis virus (MHV), porcine epidemic diarrhea virus (PEDV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), encode papain-like (PL) proteases that inhibit Sendai virus- (SeV-) induced interferon (IFN-β) production. Recently, the crystal structure of transmissible gastroenteritis virus (TGEV) PL1 has been solved, which was similar to that of SARS-CoV PL2(pro), which may antagonize host innate immunity. However, very little is known about whether TGEV PL1 can antagonize host innate immune response. Here, we presented evidence that TGEV PL1 encoded by the replicase gene could suppress the IFN-β expression and inhibit the nuclear translocation of interferon regulatory factor 3 (IRF3). The ability to antagonize IFN-β production was dependent on the intact catalytic activity of PL1. Furthermore, TGEV PL1 exerted deubiquitinase (DUB) activity which strongly inhibited the retinoic acid-induced gene I- (RIG-1-) and stimulator of interferon gene- (STING-) dependent IFN expression. Our data collectively suggest that TGEV PL1 can inhibit the IFN-β expression and interfere with RIG-1- and STING-mediated signaling through a viral DUB activity. Our study has yielded strong evidence for the TGEV PL1 mechanisms that counteract the host innate immunity.",2017 Oct 23,"['Hu, Xiaoliang', 'Tian, Jin', 'Kang, Hongtao', 'Guo, Dongchun', 'Liu, Jiasen', 'Liu, Dafei', 'Jiang, Qian', 'Li, Zhijie', 'Qu, Juanjuan', 'Qu, Liandong']",Biomed Res Int,,,True
306c2b4690eb9e399d2f301c7ca36eca27cad013,PMC,Oral immunization of a non-recombinant Lactococcus lactis surface displaying influenza hemagglutinin 1 (HA1) induces mucosal immunity in mice,http://dx.doi.org/10.1371/journal.pone.0187718,PMC5673223,29108012,CC BY,"Mucosal immunization of influenza vaccine is potentially an effective approach for the prevention and control of influenza. The objective of the present study was to evaluate the ability of oral immunization with a non-recombinant Lactococcus lactis displaying HA1/L/AcmA recombinant protein, LL-HA1/L/AcmA, to induce mucosal immune responses and to accord protection against influenza virus infection in mice. The LL-HA1/L/AcmA was orally administered into mice and the immune response was evaluated. Mice immunized with LL-HA1/L/AcmA developed detectable specific sIgA in faecal extract, small intestine wash, BAL fluid and nasal fluid. The results obtained demonstrated that oral immunization of mice with LL-HA1/L/AcmA elicited mucosal immunity in both the gastrointestinal tract and the respiratory tract. The protective efficacy of LL-HA1/L/AcmA in immunized mice against a lethal dose challenge with influenza virus was also assessed. Upon challenge, the non-immunized group of mice showed high susceptibility to influenza virus infection. In contrast, 7/8 of mice orally immunized with LL-HA1/L/AcmA survived. In conclusion, oral administration of LL-HA1/L/AcmA in mice induced mucosal immunity and most importantly, provided protection against lethal influenza virus challenge. These results highlight the potential application of L. lactis as a platform for delivery of influenza virus vaccine.",2017 Nov 6,"['Jee, Pui-Fong', 'Tiong, Vunjia', 'Shu, Meng-Hooi', 'Khoo, Jing-Jing', 'Wong, Won Fen', 'Abdul Rahim, Raha', 'AbuBakar, Sazaly', 'Chang, Li-Yen']",PLoS One,,,True
b298992d7feb9dd3d23192572f975abdf2cebc0a,PMC,Treatment with proteasome inhibitor bortezomib decreases organic anion transporting polypeptide (OATP) 1B3-mediated transport in a substrate-dependent manner,http://dx.doi.org/10.1371/journal.pone.0186924,PMC5673231,29107984,CC BY,"OATP1B1 and OATP1B3 mediate hepatic uptake of many drugs (e.g., statins) and can mediate transporter-mediated drug-drug-interactions (DDIs). Bortezomib is the first-in-class proteasome inhibitor drug approved by the U. S. Food and Drug Administration for the treatment of multiple myeloma. The potential of bortezomib to cause OATP-mediated DDIs has not been assessed. The current study investigated the involvement of the ubiquitin-proteasome system (UPS) in OATP1B1 and OATP1B3 degradation and determined the effects of proteasome inhibitors on OATP1B1- and OATP1B3-mediated transport. Co-immunoprecipitation of FLAG-OATP1B1/1B3 and HA-ubiquitin was observed in human embryonic kidney (HEK) 293 cells co-transfected with FLAG-tagged OATP1B1/OATP1B3 and hemagglutinin (HA)-tagged ubiquitin, suggesting that OATP1B1 and OATP1B3 can be ubiquitin-modified. Although blocking proteasome activity by bortezomib treatment (50 nM, 7 h) increased the endogenous ubiquitin-conjugated FLAG-OATP1B1 and FLAG-OATP1B3 in HEK293-FLAG-OATP1B1 and–OATP1B3 cells, such treatment did not affect the total protein levels of OATP1B1 and OATP1B3, suggesting that the UPS plays a minor role in degradation of OATP1B1 and OATP1B3 under current constitutive conditions. Pretreatment with bortezomib (50–250 nM, 2–7 h) significantly decreased transport of [(3)H]CCK-8, a specific OATP1B3 substrate, in HEK293-OATP1B3 and human sandwich-cultured hepatocytes (SCH). However, bortezomib pretreatment had negligible effects on the transport of [(3)H]E(2)17βG and [(3)H]pitavastatin, dual substrates of OATP1B1 and OATP1B3, in HEK293-OATP1B1/1B3 cells and/or human SCH. Compared with vehicle control treatment, bortezomib pretreatment significantly decreased the maximal transport velocity (V(max)) of OATP1B3-mediated transport of CCK-8 (92.25 ± 14.2 vs. 133.95 ± 15.5 pmol/mg protein/min) without affecting the affinity constant (K(m)) values. Treatment with other proteasome inhibitors MG132, epoxomicin, and carfilzomib also significantly decreased OATP1B3-mediated [(3)H]CCK-8 transport. In summary, the current studies for the first time report ubiquitination of OATP1B1 and OATP1B3 and the apparent substrate-dependent inhibitory effect of bortezomib on OATP1B3-mediated transport. The data suggest that bortezomib has a low risk of causing OATP-mediated DDIs.",2017 Nov 6,"['Alam, Khondoker', 'Farasyn, Taleah', 'Crowe, Alexandra', 'Ding, Kai', 'Yue, Wei']",PLoS One,,,True
a1cf22a32f52266d2805e1748ae1d6b16d16ed9f,PMC,VSIG4 inhibits proinflammatory macrophage activation by reprogramming mitochondrial pyruvate metabolism,http://dx.doi.org/10.1038/s41467-017-01327-4,PMC5673889,29109438,CC BY,"Exacerbation of macrophage-mediated inflammation contributes to pathogenesis of various inflammatory diseases, but the immunometabolic programs underlying regulation of macrophage activation are unclear. Here we show that V-set immunoglobulin-domain-containing 4 (VSIG4), a B7 family-related protein that is expressed by resting macrophages, inhibits macrophage activation in response to lipopolysaccharide. Vsig4 (−/−) mice are susceptible to high-fat diet-caused obesity and murine hepatitis virus strain-3 (MHV-3)-induced fulminant hepatitis due to excessive macrophage-dependent inflammation. VSIG4 activates the PI3K/Akt–STAT3 pathway, leading to pyruvate dehydrogenase kinase-2 (PDK2) upregulation and subsequent phosphorylation of pyruvate dehydrogenase, which results in reduction in pyruvate/acetyl-CoA conversion, mitochondrial reactive oxygen species secretion, and macrophage inhibition. Conversely, interruption of Vsig4 or Pdk2 promotes inflammation. Forced expression of Vsig4 in mice ameliorates MHV-3-induced viral fulminant hepatitis. These data show that VSIG4 negatively regulates macrophage activation by reprogramming mitochondrial pyruvate metabolism.",2017 Nov 6,"['Li, Jialin', 'Diao, Bo', 'Guo, Sheng', 'Huang, Xiaoyong', 'Yang, Chengying', 'Feng, Zeqing', 'Yan, Weiming', 'Ning, Qin', 'Zheng, Lixin', 'Chen, Yongwen', 'Wu, Yuzhang']",Nat Commun,,,False
e253bc473c9efe39820d61fc25bb1ea076d754b9,PMC,VSIG4 inhibits proinflammatory macrophage activation by reprogramming mitochondrial pyruvate metabolism,http://dx.doi.org/10.1038/s41467-017-01327-4,PMC5673889,29109438,CC BY,"Exacerbation of macrophage-mediated inflammation contributes to pathogenesis of various inflammatory diseases, but the immunometabolic programs underlying regulation of macrophage activation are unclear. Here we show that V-set immunoglobulin-domain-containing 4 (VSIG4), a B7 family-related protein that is expressed by resting macrophages, inhibits macrophage activation in response to lipopolysaccharide. Vsig4 (−/−) mice are susceptible to high-fat diet-caused obesity and murine hepatitis virus strain-3 (MHV-3)-induced fulminant hepatitis due to excessive macrophage-dependent inflammation. VSIG4 activates the PI3K/Akt–STAT3 pathway, leading to pyruvate dehydrogenase kinase-2 (PDK2) upregulation and subsequent phosphorylation of pyruvate dehydrogenase, which results in reduction in pyruvate/acetyl-CoA conversion, mitochondrial reactive oxygen species secretion, and macrophage inhibition. Conversely, interruption of Vsig4 or Pdk2 promotes inflammation. Forced expression of Vsig4 in mice ameliorates MHV-3-induced viral fulminant hepatitis. These data show that VSIG4 negatively regulates macrophage activation by reprogramming mitochondrial pyruvate metabolism.",2017 Nov 6,"['Li, Jialin', 'Diao, Bo', 'Guo, Sheng', 'Huang, Xiaoyong', 'Yang, Chengying', 'Feng, Zeqing', 'Yan, Weiming', 'Ning, Qin', 'Zheng, Lixin', 'Chen, Yongwen', 'Wu, Yuzhang']",Nat Commun,,,False
7a17153175a6479a419d62e63b6625186f6b86a0,PMC,VSIG4 inhibits proinflammatory macrophage activation by reprogramming mitochondrial pyruvate metabolism,http://dx.doi.org/10.1038/s41467-017-01327-4,PMC5673889,29109438,CC BY,"Exacerbation of macrophage-mediated inflammation contributes to pathogenesis of various inflammatory diseases, but the immunometabolic programs underlying regulation of macrophage activation are unclear. Here we show that V-set immunoglobulin-domain-containing 4 (VSIG4), a B7 family-related protein that is expressed by resting macrophages, inhibits macrophage activation in response to lipopolysaccharide. Vsig4 (−/−) mice are susceptible to high-fat diet-caused obesity and murine hepatitis virus strain-3 (MHV-3)-induced fulminant hepatitis due to excessive macrophage-dependent inflammation. VSIG4 activates the PI3K/Akt–STAT3 pathway, leading to pyruvate dehydrogenase kinase-2 (PDK2) upregulation and subsequent phosphorylation of pyruvate dehydrogenase, which results in reduction in pyruvate/acetyl-CoA conversion, mitochondrial reactive oxygen species secretion, and macrophage inhibition. Conversely, interruption of Vsig4 or Pdk2 promotes inflammation. Forced expression of Vsig4 in mice ameliorates MHV-3-induced viral fulminant hepatitis. These data show that VSIG4 negatively regulates macrophage activation by reprogramming mitochondrial pyruvate metabolism.",2017 Nov 6,"['Li, Jialin', 'Diao, Bo', 'Guo, Sheng', 'Huang, Xiaoyong', 'Yang, Chengying', 'Feng, Zeqing', 'Yan, Weiming', 'Ning, Qin', 'Zheng, Lixin', 'Chen, Yongwen', 'Wu, Yuzhang']",Nat Commun,,,True
225d47cea0dca6f6211b16f9bf8911e2360fb75b,PMC,Development of real-time recombinase polymerase amplification assay for rapid and sensitive detection of canine parvovirus 2,http://dx.doi.org/10.1186/s12917-017-1232-z,PMC5674863,29110666,CC BY,"BACKGROUND: Canine parvovirus 2, a linear single-stranded DNA virus belonging to the genus Parvovirus within the family Parvoviridae, is a highly contagious pathogen of domestic dogs and several wild canidae species. Early detection of canine parvovirus (CPV-2) is crucial to initiating appropriate outbreak control strategies. Recombinase polymerase amplification (RPA), a novel isothermal gene amplification technique, has been developed for the molecular detection of diverse pathogens. In this study, a real-time RPA assay was developed for the detection of CPV-2 using primers and an exo probe targeting the CPV-2 nucleocapsid protein gene. RESULTS: The real-time RPA assay was performed successfully at 38 °C, and the results were obtained within 4–12 min for 10(5)–10(1) molecules of template DNA. The assay only detected CPV-2, and did not show cross-detection of other viral pathogens, demonstrating a high level of specificity. The analytical sensitivity of the real-time RPA was 10(1) copies/reaction of a standard DNA template, which was 10 times more sensitive than the common RPA method. The clinical sensitivity of the real-time RPA assay matched 100% (n = 91) to the real-time PCR results. CONCLUSION: The real-time RPA assay is a simple, rapid, reliable and affordable method that can potentially be applied for the detection of CPV-2 in the research laboratory and point-of-care diagnosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-017-1232-z) contains supplementary material, which is available to authorized users.",2017 Nov 6,"['Geng, Yunyun', 'Wang, Jianchang', 'Liu, Libing', 'Lu, Yan', 'Tan, Ke', 'Chang, Yan-Zhong']",BMC Vet Res,,,True
ba394664ad45d9f543519112dcd3dc4b3a213413,PMC,Single primer isothermal amplification (SPIA) combined with next generation sequencing provides complete bovine coronavirus genome coverage and higher sequence depth compared to sequence-independent single primer amplification (SISPA),http://dx.doi.org/10.1371/journal.pone.0187780,PMC5675387,29112950,CC BY,"Coronaviruses are of major importance for both animal and human health. With the emergence of novel coronaviruses such as SARS and MERS, the need for fast genome characterisation is ever so important. Further, in order to understand the influence of quasispecies of these viruses in relation to biology, techniques for deep-sequence and full-length viral genome analysis are needed. In the present study, we compared the efficiency of two sequence-independent approaches [sequence-independent single primer amplification (SISPA) and single primer isothermal amplification (SPIA, represented by the Ovation kit)] coupled with high-throughput sequencing to generate the full-length genome of bovine coronavirus (BCoV) from a nasal swab. Both methods achieved high genome coverage (100% for SPIA and 99% for SISPA), however, there was a clear difference in the percentage of reads that mapped to BCoV. While approximately 45% of the Ovation reads mapped to BCoV (sequence depth of 169–284 944), only 0.07% of the SISPA reads (sequence depth of 0–249) mapped to the reference genome. Although BCoV was the focus of the study we also identified a bovine rhinitis B virus (BRBV) in the data sets. The trend for this virus was similar to that observed for BCoV regarding Ovation vs. SISPA, but with fewer sequences mapping to BRBV due to a lower amount of this virus. In summary, the SPIA approach used in this study produced coverage of the entire BCoV (high copy number) and BRBV (low copy number) and a high sequence/genome depth compared to SISPA. Although this is a limited study, the results indicate that the Ovation method could be a preferred approach for full genome sequencing if a low copy number of viral RNA is expected and if high sequence depth is desired.",2017 Nov 7,"['Myrmel, Mette', 'Oma, Veslemøy', 'Khatri, Mamata', 'Hansen, Hanne H.', 'Stokstad, Maria', 'Berg, Mikael', 'Blomström, Anne-Lie']",PLoS One,,,True
fd8ee38a505cf79732f5ba487e15f11619b84150,PMC,Epidemiologic characteristics of scrub typhus on Jeju Island,http://dx.doi.org/10.4178/epih.e2017039,PMC5675983,28823118,CC BY,"OBJECTIVES: Scrub typhus is the most common febrile disease in Korea during the autumn. Jeju Island is the largest island in South Korea and has a distinctive oceanic climate. This study aimed to identify epidemiologic characteristics of scrub typhus on Jeju Island. METHODS: From January 2011 to December 2016, 446 patients were diagnosed with scrub typhus on Jeju Island. The patients’ personal data and the environmental factors that might be related to scrub typhus were investigated and retrospectively analyzed. RESULTS: The median age of the patients was 58-years-old (range, 8 to 91) and 43% of them worked in the agricultural, forestry or livestock industry. Regardless of their job, 87% of the patients had a history of either working outdoors or of other activities before developing scrub typhus. The south and southeast regions of Jeju Island, especially Namwon-eup, showed the highest incidence of scrub typhus. Workers in mandarin orange orchards seemed to be the highest risk group for scrub typhus infection. CONCLUSIONS: Scrub typhus on Jeju Island showed unique characteristics. To efficiently prevent scrub typhus, each year individual regional approaches should be developed based on the epidemiologic characteristics of the disease.",2017 Aug 18,"Lee, Sung Uk",Epidemiol Health,,,True
146fa23813d36d8da4ea4ab928d5cac594fdbd44,PMC,Epidemiologic characteristics of scrub typhus on Jeju Island,http://dx.doi.org/10.4178/epih.e2017039,PMC5675983,28823118,CC BY,"OBJECTIVES: Scrub typhus is the most common febrile disease in Korea during the autumn. Jeju Island is the largest island in South Korea and has a distinctive oceanic climate. This study aimed to identify epidemiologic characteristics of scrub typhus on Jeju Island. METHODS: From January 2011 to December 2016, 446 patients were diagnosed with scrub typhus on Jeju Island. The patients’ personal data and the environmental factors that might be related to scrub typhus were investigated and retrospectively analyzed. RESULTS: The median age of the patients was 58-years-old (range, 8 to 91) and 43% of them worked in the agricultural, forestry or livestock industry. Regardless of their job, 87% of the patients had a history of either working outdoors or of other activities before developing scrub typhus. The south and southeast regions of Jeju Island, especially Namwon-eup, showed the highest incidence of scrub typhus. Workers in mandarin orange orchards seemed to be the highest risk group for scrub typhus infection. CONCLUSIONS: Scrub typhus on Jeju Island showed unique characteristics. To efficiently prevent scrub typhus, each year individual regional approaches should be developed based on the epidemiologic characteristics of the disease.",2017 Aug 18,"Lee, Sung Uk",Epidemiol Health,,,True
9d689209d9886db326dc65759ef929ac56832d93,PMC,Infectious disease-related laws: prevention and control measures,http://dx.doi.org/10.4178/epih.e2017033,PMC5675986,28774161,CC BY,"OBJECTIVES: This study examines recently revised Korean government legislation addressing global infectious disease control for public health emergency situations, with the aim of proposing more rational, effective and realistic interpretations and applications for improvement of law. METHODS: The Korea reported its first laboratory-confirmed case of Middle East Respiratory Syndrome (MERS) coronavirus on May 20, 2015. Since the first indexed case, Korean public health authorities enforced many public health measures that were not authorized in the law; the scope of the current law was too limited to cover MERS. Korea has three levels of government: the central government, special self-governing provinces, and si/gun/gu. Unfortunately, the Infectious Disease Control and Prevention Act does not designate the specific roles of each level of government, and does not state how these governmental branches should be vertically integrated in a state of emergency. RESULTS: When thinking about these policy questions, we should be especially concerned about introducing a new act that deals with all matters relevant to emerging infectious diseases. The aim would be to develop a structure that specifies the roles of each level of government, and facilitates the close collaboration among them, then enacting this in law for the prevention and response of infectious disease. CONCLUSIONS: To address this problem, after analyzing the national healthcare infrastructure along with the characteristics of emerging infectious diseases, we propose the revision of the relevant law(s) in terms of governance aspects, emergency medical countermeasure aspects, and the human rights aspect.",2017 Jul 25,"Park, Mijeong",Epidemiol Health,,,True
cf47b85324ae854a471893563d2156f4a47632e9,PMC,Infectious disease-related laws: prevention and control measures,http://dx.doi.org/10.4178/epih.e2017033,PMC5675986,28774161,CC BY,"OBJECTIVES: This study examines recently revised Korean government legislation addressing global infectious disease control for public health emergency situations, with the aim of proposing more rational, effective and realistic interpretations and applications for improvement of law. METHODS: The Korea reported its first laboratory-confirmed case of Middle East Respiratory Syndrome (MERS) coronavirus on May 20, 2015. Since the first indexed case, Korean public health authorities enforced many public health measures that were not authorized in the law; the scope of the current law was too limited to cover MERS. Korea has three levels of government: the central government, special self-governing provinces, and si/gun/gu. Unfortunately, the Infectious Disease Control and Prevention Act does not designate the specific roles of each level of government, and does not state how these governmental branches should be vertically integrated in a state of emergency. RESULTS: When thinking about these policy questions, we should be especially concerned about introducing a new act that deals with all matters relevant to emerging infectious diseases. The aim would be to develop a structure that specifies the roles of each level of government, and facilitates the close collaboration among them, then enacting this in law for the prevention and response of infectious disease. CONCLUSIONS: To address this problem, after analyzing the national healthcare infrastructure along with the characteristics of emerging infectious diseases, we propose the revision of the relevant law(s) in terms of governance aspects, emergency medical countermeasure aspects, and the human rights aspect.",2017 Jul 25,"Park, Mijeong",Epidemiol Health,,,True
2efafa52eab6095a1d2e48ae5acd7f295b634db2,PMC,The direction of restructuring of a Korea field epidemiology training program through questionnaire survey among communicable disease response staff in Korea,http://dx.doi.org/10.4178/epih.e2017032,PMC5675987,28774162,CC BY,"We used a survey about the need for an educational training of infectious disease response staff in Korea Centers for Disease Control and Prevention (KCDC) and officer in metropolitan cities and provincial government to conduct field epidemiological investigation. The survey was conducted from January 25 to March 15, 2016. A total of 173 participants were selected from four different groups as follows: 27 clinical specialists, 22 Epidemic Intelligence Service (EIS) officers, 82 KCDC staff, and 42 local health department officials. Results revealed that 83% of KCDC staff and 95% of local health department officials agreed on the need for educational training to strengthen capability of personnel to conduct epidemic research and investigation. The level of their need for training was relatively high, while self-confidence levels of individuals to conduct epidemic research and investigation was low. It was concluded that there was a need to develop training programs to enhance the ability of public health officials, EIS officers, KCDC staff, and local health department personnel to conduct epidemic research and investigation.",2017 Jul 24,"['Lee, Moo-Sik', 'Lee, Kwan', 'Park, Ji-Hyuk', 'Hong, Jee-Young', 'Jang, Min Young', 'Jeon, Byoung-Hak', 'Cho, Sang Yun', 'Choi, Sun Ja', 'Hong, Jeong Ik']",Epidemiol Health,,,True
a4f3e08e12cadc025f14c7a3f0d6cf3241e0375c,PMC,The direction of restructuring of a Korea field epidemiology training program through questionnaire survey among communicable disease response staff in Korea,http://dx.doi.org/10.4178/epih.e2017032,PMC5675987,28774162,CC BY,"We used a survey about the need for an educational training of infectious disease response staff in Korea Centers for Disease Control and Prevention (KCDC) and officer in metropolitan cities and provincial government to conduct field epidemiological investigation. The survey was conducted from January 25 to March 15, 2016. A total of 173 participants were selected from four different groups as follows: 27 clinical specialists, 22 Epidemic Intelligence Service (EIS) officers, 82 KCDC staff, and 42 local health department officials. Results revealed that 83% of KCDC staff and 95% of local health department officials agreed on the need for educational training to strengthen capability of personnel to conduct epidemic research and investigation. The level of their need for training was relatively high, while self-confidence levels of individuals to conduct epidemic research and investigation was low. It was concluded that there was a need to develop training programs to enhance the ability of public health officials, EIS officers, KCDC staff, and local health department personnel to conduct epidemic research and investigation.",2017 Jul 24,"['Lee, Moo-Sik', 'Lee, Kwan', 'Park, Ji-Hyuk', 'Hong, Jee-Young', 'Jang, Min Young', 'Jeon, Byoung-Hak', 'Cho, Sang Yun', 'Choi, Sun Ja', 'Hong, Jeong Ik']",Epidemiol Health,,,True
e27b2ec189028052ab97b7b959087ac012222a98,PMC,Proofreading-Deficient Coronaviruses Adapt for Increased Fitness over Long-Term Passage without Reversion of Exoribonuclease-Inactivating Mutations,http://dx.doi.org/10.1128/mBio.01503-17,PMC5676041,29114026,CC BY,"The coronavirus (CoV) RNA genome is the largest among the single-stranded positive-sense RNA viruses. CoVs encode a proofreading 3′-to-5′ exoribonuclease within nonstructural protein 14 (nsp14-ExoN) that is responsible for CoV high-fidelity replication. Alanine substitution of ExoN catalytic residues [ExoN(-)] in severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and murine hepatitis virus (MHV) disrupts ExoN activity, yielding viable mutant viruses with defective replication, up to 20-fold-decreased fidelity, and increased susceptibility to nucleoside analogues. To test the stability of the ExoN(-) genotype and phenotype, we passaged MHV-ExoN(-) 250 times in cultured cells (P250), in parallel with wild-type MHV (WT-MHV). Compared to MHV-ExoN(-) P3, MHV-ExoN(-) P250 demonstrated enhanced replication and increased competitive fitness without reversion at the ExoN(-) active site. Furthermore, MHV-ExoN(-) P250 was less susceptible than MHV-ExoN(-) P3 to multiple nucleoside analogues, suggesting that MHV-ExoN(-) was under selection for increased replication fidelity. We subsequently identified novel amino acid changes within the RNA-dependent RNA polymerase and nsp14 of MHV-ExoN(-) P250 that partially accounted for the reduced susceptibility to nucleoside analogues. Our results suggest that increased replication fidelity is selected in ExoN(-) CoVs and that there may be a significant barrier to ExoN(-) reversion. These results also support the hypothesis that high-fidelity replication is linked to CoV fitness and indicate that multiple replicase proteins could compensate for ExoN functions during replication.",2017 Nov 7,"['Graepel, Kevin W.', 'Lu, Xiaotao', 'Case, James Brett', 'Sexton, Nicole R.', 'Smith, Everett Clinton', 'Denison, Mark R.']",mBio,,,True
2181545c5d410c36f7a2e011f9fe1d706d9cc693,PMC,Proofreading-Deficient Coronaviruses Adapt for Increased Fitness over Long-Term Passage without Reversion of Exoribonuclease-Inactivating Mutations,http://dx.doi.org/10.1128/mBio.01503-17,PMC5676041,29114026,CC BY,"The coronavirus (CoV) RNA genome is the largest among the single-stranded positive-sense RNA viruses. CoVs encode a proofreading 3′-to-5′ exoribonuclease within nonstructural protein 14 (nsp14-ExoN) that is responsible for CoV high-fidelity replication. Alanine substitution of ExoN catalytic residues [ExoN(-)] in severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and murine hepatitis virus (MHV) disrupts ExoN activity, yielding viable mutant viruses with defective replication, up to 20-fold-decreased fidelity, and increased susceptibility to nucleoside analogues. To test the stability of the ExoN(-) genotype and phenotype, we passaged MHV-ExoN(-) 250 times in cultured cells (P250), in parallel with wild-type MHV (WT-MHV). Compared to MHV-ExoN(-) P3, MHV-ExoN(-) P250 demonstrated enhanced replication and increased competitive fitness without reversion at the ExoN(-) active site. Furthermore, MHV-ExoN(-) P250 was less susceptible than MHV-ExoN(-) P3 to multiple nucleoside analogues, suggesting that MHV-ExoN(-) was under selection for increased replication fidelity. We subsequently identified novel amino acid changes within the RNA-dependent RNA polymerase and nsp14 of MHV-ExoN(-) P250 that partially accounted for the reduced susceptibility to nucleoside analogues. Our results suggest that increased replication fidelity is selected in ExoN(-) CoVs and that there may be a significant barrier to ExoN(-) reversion. These results also support the hypothesis that high-fidelity replication is linked to CoV fitness and indicate that multiple replicase proteins could compensate for ExoN functions during replication.",2017 Nov 7,"['Graepel, Kevin W.', 'Lu, Xiaotao', 'Case, James Brett', 'Sexton, Nicole R.', 'Smith, Everett Clinton', 'Denison, Mark R.']",mBio,,,False
d16469715ed35b2456b21d451d933bedf48da9ff,PMC,Proofreading-Deficient Coronaviruses Adapt for Increased Fitness over Long-Term Passage without Reversion of Exoribonuclease-Inactivating Mutations,http://dx.doi.org/10.1128/mBio.01503-17,PMC5676041,29114026,CC BY,"The coronavirus (CoV) RNA genome is the largest among the single-stranded positive-sense RNA viruses. CoVs encode a proofreading 3′-to-5′ exoribonuclease within nonstructural protein 14 (nsp14-ExoN) that is responsible for CoV high-fidelity replication. Alanine substitution of ExoN catalytic residues [ExoN(-)] in severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and murine hepatitis virus (MHV) disrupts ExoN activity, yielding viable mutant viruses with defective replication, up to 20-fold-decreased fidelity, and increased susceptibility to nucleoside analogues. To test the stability of the ExoN(-) genotype and phenotype, we passaged MHV-ExoN(-) 250 times in cultured cells (P250), in parallel with wild-type MHV (WT-MHV). Compared to MHV-ExoN(-) P3, MHV-ExoN(-) P250 demonstrated enhanced replication and increased competitive fitness without reversion at the ExoN(-) active site. Furthermore, MHV-ExoN(-) P250 was less susceptible than MHV-ExoN(-) P3 to multiple nucleoside analogues, suggesting that MHV-ExoN(-) was under selection for increased replication fidelity. We subsequently identified novel amino acid changes within the RNA-dependent RNA polymerase and nsp14 of MHV-ExoN(-) P250 that partially accounted for the reduced susceptibility to nucleoside analogues. Our results suggest that increased replication fidelity is selected in ExoN(-) CoVs and that there may be a significant barrier to ExoN(-) reversion. These results also support the hypothesis that high-fidelity replication is linked to CoV fitness and indicate that multiple replicase proteins could compensate for ExoN functions during replication.",2017 Nov 7,"['Graepel, Kevin W.', 'Lu, Xiaotao', 'Case, James Brett', 'Sexton, Nicole R.', 'Smith, Everett Clinton', 'Denison, Mark R.']",mBio,,,False
2d1d4b3eee10123a6c8567dbac2705659b8047bc,PMC,"Strengthening National Disease Surveillance and Response—Haiti, 2010–2015",http://dx.doi.org/10.4269/ajtmh.16-0948,PMC5676630,29064361,CC BY,"Haiti’s health system has faced many challenges over the years, with competing health priorities in the context of chronic financial and human resource limitations. As a result, the existing notifiable disease surveillance system was unable to provide the most basic epidemiologic data for public health decision-making and action. In the wake of the January 2010 earthquake, the Haitian Ministry of Public Health and Population collaborated with the U.S. Centers for Disease Control and Prevention, the Pan American Health Organization, and other local and international partners to implement a functional national surveillance system. More than 7 years later, it is important to take the opportunity to reflect on progress made on surveillance and response in Haiti, including disease detection, reporting, outbreak investigation, and response. The national epidemiologic surveillance network that started with 51 sites in 2010 has been expanded to 357 sites as of December 2015. Disease outbreaks identified via the surveillance system, or other surveillance approaches, are investigated by epidemiologists trained by the Ministry of Health’s Field Epidemiology Training Program. Other related surveillance modules have been developed on the same model and electronic platform, allowing the country to document the impact of interventions, track progress, and monitor health problems. Sustainability remains the greatest challenge since most of the funding for surveillance come from external sources.",2017 Oct 18,"['Juin, Stanley', 'Schaad, Nicolas', 'Lafontant, Donald', 'Joseph, Gerard A.', 'Barzilay, Ezra', 'Boncy, Jacques', 'Barrais, Robert', 'Louis, Frantz Jean', 'Jean Charles, Nadia Lapierre', 'Corvil, Salomon', 'Barthelemy, Nickolsno', 'Dismer, Amber', 'Pierre, Jean Samuel', 'Archer, Roodly W.', 'Antoine, Mayer', 'Marston, Barbara', 'Katz, Mark', 'Dely, Patrick', 'Adrien, Paul', 'Fitter, David L.', 'Lowrance, David', 'Patel, Roopal']",Am J Trop Med Hyg,,,True
6ec5ee2681be3633672ac2d32249110514289a5c,PMC,Novel prostate cancer immunotherapy with a DNA-encoded anti-prostate-specific membrane antigen monoclonal antibody,http://dx.doi.org/10.1007/s00262-017-2042-7,PMC5676807,28819703,CC BY,"Prostate-specific membrane antigen (PSMA) is expressed at high levels on malignant prostate cells and is likely an important therapeutic target for the treatment of prostate carcinoma. Current immunotherapy approaches to target PSMA include peptide, cell, vector or DNA-based vaccines as well as passive administration of PSMA-specific monoclonal antibodies (mAb). Conventional mAb immunotherapy has numerous logistical and practical limitations, including high production costs and a requirement for frequent dosing due to short mAb serum half-life. In this report, we describe a novel strategy of antibody-based immunotherapy against prostate carcinoma that utilizes synthetic DNA plasmids that encode a therapeutic human mAb that target PSMA. Electroporation-enhanced intramuscular injection of the DNA-encoded mAb (DMAb) plasmid into mice led to the production of functional and durable levels of the anti-PSMA antibody. The anti-PSMA produced in vivo controlled tumor growth and prolonged survival in a mouse model. This is likely mediated by antibody-dependent cellular cytotoxicity (ADCC) effect with the aid of NK cells. Further study of  this novel approach for treatment of human prostate disease and other malignant conditions is warranted.",2017 Aug 17,"['Muthumani, Kar', 'Marnin, Liron', 'Kudchodkar, Sagar B.', 'Perales-Puchalt, Alfredo', 'Choi, Hyeree', 'Agarwal, Sangya', 'Scott, Veronica L.', 'Reuschel, Emma L.', 'Zaidi, Faraz I.', 'Duperret, Elizabeth K.', 'Wise, Megan C.', 'Kraynyak, Kimberly A.', 'Ugen, Kenneth. E.', 'Sardesai, Niranjan Y.', 'Joseph Kim, J.', 'Weiner, David B.']",Cancer Immunol Immunother,,,True
194e09560f46554663015f54423f7f5d7822025b,PMC,Recent Advances in Nanoparticle Concentration and Their Application in Viral Detection Using Integrated Sensors,http://dx.doi.org/10.3390/s17102316,PMC5677234,29019959,CC BY,"Early disease diagnostics require rapid, sensitive, and selective detection methods for target analytes. Specifically, early viral detection in a point-of-care setting is critical in preventing epidemics and the spread of disease. However, conventional methods such as enzyme-linked immunosorbent assays or cell cultures are cumbersome and difficult for field use due to the requirements of extensive lab equipment and highly trained personnel, as well as limited sensitivity. Recent advances in nanoparticle concentration have given rise to many novel detection methodologies, which address the shortcomings in modern clinical assays. Here, we review the primary, well-characterized methods for nanoparticle concentration in the context of viral detection via diffusion, centrifugation and microfiltration, electric and magnetic fields, and nano-microfluidics. Details of the concentration mechanisms and examples of related applications provide valuable information to design portable, integrated sensors. This study reviews a wide range of concentration techniques and compares their advantages and disadvantages with respect to viral particle detection. We conclude by highlighting selected concentration methods and devices for next-generation biosensing systems.",2017 Oct 11,"['Dincau, Brian M.', 'Lee, Yongkuk', 'Kim, Jong-Hoon', 'Yeo, Woon-Hong']",Sensors (Basel),,,True
21acb307a82957e94b99eb1afdcc459b2ca53582,PMC,Myeloablation-associated deletion of ORF4 in a human coronavirus 229E infection,http://dx.doi.org/10.1038/s41525-017-0033-4,PMC5677986,29263840,CC BY,"We describe metagenomic next-generation sequencing (mNGS) of a human coronavirus 229E from a patient with AML and persistent upper respiratory symptoms, who underwent hematopoietic cell transplantation (HCT). mNGS revealed a 548-nucleotide deletion, which comprised the near entirety of the ORF4 gene, and no minor allele variants were detected to suggest a mixed infection. As part of her pre-HCT conditioning regimen, the patient received myeloablative treatment with cyclophosphamide and 12 Gy total body irradiation. Iterative sequencing and RT-PCR confirmation of four respiratory samples over the 4-week peritransplant period revealed that the pre-conditioning strain contained an intact ORF4 gene, while the deletion strain appeared just after conditioning and persisted over a 2.5-week period. This sequence represents one of the largest genomic deletions detected in a human RNA virus and describes large-scale viral mutation associated with myeloablation for HCT.",2017 Oct 9,"['Greninger, Alexander L.', 'Pepper, Gregory', 'Shean, Ryan C.', 'Cent, Anne', 'Palileo, Isabel', 'Kuypers, Jane M.', 'Schiffer, Joshua T.', 'Jerome, Keith R.']",NPJ Genom Med,,,False
e5ec05c6d25d098703bee2ff49b0e02d0bfa9de5,PMC,Myeloablation-associated deletion of ORF4 in a human coronavirus 229E infection,http://dx.doi.org/10.1038/s41525-017-0033-4,PMC5677986,29263840,CC BY,"We describe metagenomic next-generation sequencing (mNGS) of a human coronavirus 229E from a patient with AML and persistent upper respiratory symptoms, who underwent hematopoietic cell transplantation (HCT). mNGS revealed a 548-nucleotide deletion, which comprised the near entirety of the ORF4 gene, and no minor allele variants were detected to suggest a mixed infection. As part of her pre-HCT conditioning regimen, the patient received myeloablative treatment with cyclophosphamide and 12 Gy total body irradiation. Iterative sequencing and RT-PCR confirmation of four respiratory samples over the 4-week peritransplant period revealed that the pre-conditioning strain contained an intact ORF4 gene, while the deletion strain appeared just after conditioning and persisted over a 2.5-week period. This sequence represents one of the largest genomic deletions detected in a human RNA virus and describes large-scale viral mutation associated with myeloablation for HCT.",2017 Oct 9,"['Greninger, Alexander L.', 'Pepper, Gregory', 'Shean, Ryan C.', 'Cent, Anne', 'Palileo, Isabel', 'Kuypers, Jane M.', 'Schiffer, Joshua T.', 'Jerome, Keith R.']",NPJ Genom Med,,,False
88e08bc082011875a44d644d378e876289ac9410,PMC,Myeloablation-associated deletion of ORF4 in a human coronavirus 229E infection,http://dx.doi.org/10.1038/s41525-017-0033-4,PMC5677986,29263840,CC BY,"We describe metagenomic next-generation sequencing (mNGS) of a human coronavirus 229E from a patient with AML and persistent upper respiratory symptoms, who underwent hematopoietic cell transplantation (HCT). mNGS revealed a 548-nucleotide deletion, which comprised the near entirety of the ORF4 gene, and no minor allele variants were detected to suggest a mixed infection. As part of her pre-HCT conditioning regimen, the patient received myeloablative treatment with cyclophosphamide and 12 Gy total body irradiation. Iterative sequencing and RT-PCR confirmation of four respiratory samples over the 4-week peritransplant period revealed that the pre-conditioning strain contained an intact ORF4 gene, while the deletion strain appeared just after conditioning and persisted over a 2.5-week period. This sequence represents one of the largest genomic deletions detected in a human RNA virus and describes large-scale viral mutation associated with myeloablation for HCT.",2017 Oct 9,"['Greninger, Alexander L.', 'Pepper, Gregory', 'Shean, Ryan C.', 'Cent, Anne', 'Palileo, Isabel', 'Kuypers, Jane M.', 'Schiffer, Joshua T.', 'Jerome, Keith R.']",NPJ Genom Med,,,False
da38234a5ddf7e9d8d468b64e942a50bf164e924,PMC,Myeloablation-associated deletion of ORF4 in a human coronavirus 229E infection,http://dx.doi.org/10.1038/s41525-017-0033-4,PMC5677986,29263840,CC BY,"We describe metagenomic next-generation sequencing (mNGS) of a human coronavirus 229E from a patient with AML and persistent upper respiratory symptoms, who underwent hematopoietic cell transplantation (HCT). mNGS revealed a 548-nucleotide deletion, which comprised the near entirety of the ORF4 gene, and no minor allele variants were detected to suggest a mixed infection. As part of her pre-HCT conditioning regimen, the patient received myeloablative treatment with cyclophosphamide and 12 Gy total body irradiation. Iterative sequencing and RT-PCR confirmation of four respiratory samples over the 4-week peritransplant period revealed that the pre-conditioning strain contained an intact ORF4 gene, while the deletion strain appeared just after conditioning and persisted over a 2.5-week period. This sequence represents one of the largest genomic deletions detected in a human RNA virus and describes large-scale viral mutation associated with myeloablation for HCT.",2017 Oct 9,"['Greninger, Alexander L.', 'Pepper, Gregory', 'Shean, Ryan C.', 'Cent, Anne', 'Palileo, Isabel', 'Kuypers, Jane M.', 'Schiffer, Joshua T.', 'Jerome, Keith R.']",NPJ Genom Med,,,True
bc04647c4db146a7078e6de38873824a95e99314,PMC,No evidence of enteric viral involvement in the new neonatal porcine diarrhoea syndrome in Danish pigs,http://dx.doi.org/10.1186/s12917-017-1239-5,PMC5678564,29115952,CC BY,"BACKGROUND: The aim of this study was to investigate whether the syndrome New Neonatal Porcine Diarrhoea Syndrome (NNPDS) is associated with a viral aetiology. Four well-managed herds experiencing neonatal diarrhoea and suspected to be affected by NNPDS were included in a case-control set up. A total of 989 piglets were clinically examined on a daily basis. Samples from diarrhoeic and non-diarrhoeic piglets at the age of three to seven days were selected for extensive virological examination using specific real time polymerase chain reactions (qPCRs) and general virus detection methods. RESULTS: A total of 91.7% of the animals tested positive by reverse transcription qPCR (RT-qPCR) for porcine kobuvirus 1 (PKV-1) while 9% and 3% were found to be positive for rotavirus A and porcine teschovirus (PTV), respectively. The overall prevalence of porcine astrovirus (PAstV) was 75% with 69.8% of the PAstV positive pigs infected with PAstV type 3. No animals tested positive for rotavirus C, coronavirus (TGEV, PEDV and PRCV), sapovirus, enterovirus, parechovirus, saffoldvirus, cosavirus, klassevirus or porcine circovirus type 2 (PCV2). Microarray analyses performed on a total of 18 animals were all negative, as were eight animals examined by Transmission Electron Microscopy (TEM). Using Next Generation de novo sequencing (de novo NGS) on pools of samples from case animals within all herds, PKV-1 was detected in four herds and rotavirus A, rotavirus C and PTV were detected in one herd each. CONCLUSIONS: Our detailed analyses of piglets from NNPDS-affected herds demonstrated that viruses did not pose a significant contribution to NNPDS. However, further investigations are needed to investigate if a systemic virus infection plays a role in the pathogenesis of NNPDS.",2017 Nov 7,"['Goecke, N. B.', 'Hjulsager, C. K.', 'Kongsted, H.', 'Boye, M.', 'Rasmussen, S.', 'Granberg, F.', 'Fischer, T. K.', 'Midgley, S. E.', 'Rasmussen, L. D.', 'Angen, Ø.', 'Nielsen, J. P.', 'Jorsal, S. E.', 'Larsen, L. E.']",BMC Vet Res,,,True
3b5ed157604556a2ca4dbca1d51bddfca4e1e3b4,PMC,RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination,http://dx.doi.org/10.1186/s12915-017-0444-9,PMC5678581,29117863,CC BY,"BACKGROUND: TRIM25 is a novel RNA-binding protein and a member of the Tripartite Motif (TRIM) family of E3 ubiquitin ligases, which plays a pivotal role in the innate immune response. However, there is scarce knowledge about its RNA-related roles in cell biology. Furthermore, its RNA-binding domain has not been characterized. RESULTS: Here, we reveal that the RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain, which we postulate to be a novel RNA-binding domain. Using CLIP-seq and SILAC-based co-immunoprecipitation assays, we uncover TRIM25’s endogenous RNA targets and protein binding partners. We demonstrate that TRIM25 controls the levels of Zinc Finger Antiviral Protein (ZAP). Finally, we show that the RNA-binding activity of TRIM25 is important for its ubiquitin ligase activity towards itself (autoubiquitination) and its physiologically relevant target ZAP. CONCLUSIONS: Our results suggest that many other proteins with the PRY/SPRY domain could have yet uncharacterized RNA-binding potential. Together, our data reveal new insights into the molecular roles and characteristics of RNA-binding E3 ubiquitin ligases and demonstrate that RNA could be an essential factor in their enzymatic activity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12915-017-0444-9) contains supplementary material, which is available to authorized users.",2017 Nov 8,"['Choudhury, Nila Roy', 'Heikel, Gregory', 'Trubitsyna, Maryia', 'Kubik, Peter', 'Nowak, Jakub Stanislaw', 'Webb, Shaun', 'Granneman, Sander', 'Spanos, Christos', 'Rappsilber, Juri', 'Castello, Alfredo', 'Michlewski, Gracjan']",BMC Biol,,,False
a71b7e4060dbc1160df90e7bff684d05b2cbc089,PMC,RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination,http://dx.doi.org/10.1186/s12915-017-0444-9,PMC5678581,29117863,CC BY,"BACKGROUND: TRIM25 is a novel RNA-binding protein and a member of the Tripartite Motif (TRIM) family of E3 ubiquitin ligases, which plays a pivotal role in the innate immune response. However, there is scarce knowledge about its RNA-related roles in cell biology. Furthermore, its RNA-binding domain has not been characterized. RESULTS: Here, we reveal that the RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain, which we postulate to be a novel RNA-binding domain. Using CLIP-seq and SILAC-based co-immunoprecipitation assays, we uncover TRIM25’s endogenous RNA targets and protein binding partners. We demonstrate that TRIM25 controls the levels of Zinc Finger Antiviral Protein (ZAP). Finally, we show that the RNA-binding activity of TRIM25 is important for its ubiquitin ligase activity towards itself (autoubiquitination) and its physiologically relevant target ZAP. CONCLUSIONS: Our results suggest that many other proteins with the PRY/SPRY domain could have yet uncharacterized RNA-binding potential. Together, our data reveal new insights into the molecular roles and characteristics of RNA-binding E3 ubiquitin ligases and demonstrate that RNA could be an essential factor in their enzymatic activity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12915-017-0444-9) contains supplementary material, which is available to authorized users.",2017 Nov 8,"['Choudhury, Nila Roy', 'Heikel, Gregory', 'Trubitsyna, Maryia', 'Kubik, Peter', 'Nowak, Jakub Stanislaw', 'Webb, Shaun', 'Granneman, Sander', 'Spanos, Christos', 'Rappsilber, Juri', 'Castello, Alfredo', 'Michlewski, Gracjan']",BMC Biol,,,True
bce32aefbab5d53c5751d45bc73f7623f2f58b6a,PMC,Increasing the CpG dinucleotide abundance in the HIV-1 genomic RNA inhibits viral replication,http://dx.doi.org/10.1186/s12977-017-0374-1,PMC5679385,29121951,CC BY,"BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) structural protein Gag is necessary and sufficient to form viral particles. In addition to encoding the amino acid sequence for Gag, the underlying RNA sequence could encode cis-acting elements or nucleotide biases that are necessary for viral replication. Furthermore, RNA sequences that inhibit viral replication could be suppressed in gag. However, the functional relevance of RNA elements and nucleotide biases that promote or repress HIV-1 replication remain poorly understood. RESULTS: To characterize if the RNA sequence in gag controls HIV-1 replication, the matrix (MA) region was codon modified, allowing the RNA sequence to be altered without affecting the protein sequence. Codon modification of nucleotides (nt) 22-261 or 22-378 in gag inhibited viral replication by decreasing genomic RNA (gRNA) abundance, gRNA stability, Gag expression, virion production and infectivity. Comparing the effect of these point mutations to deletions of the same region revealed that the mutations inhibited infectious virus production while the deletions did not. This demonstrated that codon modification introduced inhibitory sequences. There is a much lower than expected frequency of CpG dinucleotides in HIV-1 and codon modification introduced a substantial increase in CpG abundance. To determine if they are necessary for inhibition of HIV-1 replication, codons introducing CpG dinucleotides were mutated back to the wild type codon, which restored efficient Gag expression and infectious virion production. To determine if they are sufficient to inhibit viral replication, CpG dinucleotides were inserted into gag in the absence of other changes. The increased CpG dinucleotide content decreased HIV-1 infectivity and viral replication. CONCLUSIONS: The HIV-1 RNA sequence contains low abundance of CpG dinucleotides. Increasing the abundance of CpG dinucleotides inhibits multiple steps of the viral life cycle, providing a functional explanation for why CpG dinucleotides are suppressed in HIV-1. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12977-017-0374-1) contains supplementary material, which is available to authorized users.",2017 Nov 9,"['Antzin-Anduetza, Irati', 'Mahiet, Charlotte', 'Granger, Luke A.', 'Odendall, Charlotte', 'Swanson, Chad M.']",Retrovirology,,,False
96c9c57127b558f145ddd7d2566a427f7d12592e,PMC,Increasing the CpG dinucleotide abundance in the HIV-1 genomic RNA inhibits viral replication,http://dx.doi.org/10.1186/s12977-017-0374-1,PMC5679385,29121951,CC BY,"BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) structural protein Gag is necessary and sufficient to form viral particles. In addition to encoding the amino acid sequence for Gag, the underlying RNA sequence could encode cis-acting elements or nucleotide biases that are necessary for viral replication. Furthermore, RNA sequences that inhibit viral replication could be suppressed in gag. However, the functional relevance of RNA elements and nucleotide biases that promote or repress HIV-1 replication remain poorly understood. RESULTS: To characterize if the RNA sequence in gag controls HIV-1 replication, the matrix (MA) region was codon modified, allowing the RNA sequence to be altered without affecting the protein sequence. Codon modification of nucleotides (nt) 22-261 or 22-378 in gag inhibited viral replication by decreasing genomic RNA (gRNA) abundance, gRNA stability, Gag expression, virion production and infectivity. Comparing the effect of these point mutations to deletions of the same region revealed that the mutations inhibited infectious virus production while the deletions did not. This demonstrated that codon modification introduced inhibitory sequences. There is a much lower than expected frequency of CpG dinucleotides in HIV-1 and codon modification introduced a substantial increase in CpG abundance. To determine if they are necessary for inhibition of HIV-1 replication, codons introducing CpG dinucleotides were mutated back to the wild type codon, which restored efficient Gag expression and infectious virion production. To determine if they are sufficient to inhibit viral replication, CpG dinucleotides were inserted into gag in the absence of other changes. The increased CpG dinucleotide content decreased HIV-1 infectivity and viral replication. CONCLUSIONS: The HIV-1 RNA sequence contains low abundance of CpG dinucleotides. Increasing the abundance of CpG dinucleotides inhibits multiple steps of the viral life cycle, providing a functional explanation for why CpG dinucleotides are suppressed in HIV-1. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12977-017-0374-1) contains supplementary material, which is available to authorized users.",2017 Nov 9,"['Antzin-Anduetza, Irati', 'Mahiet, Charlotte', 'Granger, Luke A.', 'Odendall, Charlotte', 'Swanson, Chad M.']",Retrovirology,,,True
554f6f5ca9031e8c6dd85eb32f3ad3e6c222c18f,PMC,Epidemic spreading in multiplex networks influenced by opinion exchanges on vaccination,http://dx.doi.org/10.1371/journal.pone.0186492,PMC5679524,29121056,CC BY,"Through years, the use of vaccines has always been a controversial issue. People in a society may have different opinions about how beneficial the vaccines are and as a consequence some of those individuals decide to vaccinate or not themselves and their relatives. This attitude in face of vaccines has clear consequences in the spread of diseases and their transformation in epidemics. Motivated by this scenario, we study, in a simultaneous way, the changes of opinions about vaccination together with the evolution of a disease. In our model we consider a multiplex network consisting of two layers. One of the layers corresponds to a social network where people share their opinions and influence others opinions. The social model that rules the dynamic is the M-model, which takes into account two different processes that occurs in a society: persuasion and compromise. This two processes are related through a parameter r, r < 1 describes a moderate and committed society, for r > 1 the society tends to have extremist opinions, while r = 1 represents a neutral society. This social network may be of real or virtual contacts. On the other hand, the second layer corresponds to a network of physical contacts where the disease spreading is described by the SIR-Model. In this model the individuals may be in one of the following four states: Susceptible (S), Infected(I), Recovered (R) or Vaccinated (V). A Susceptible individual can: i) get vaccinated, if his opinion in the other layer is totally in favor of the vaccine, ii) get infected, with probability β if he is in contact with an infected neighbor. Those I individuals recover after a certain period t(r) = 6. Vaccinated individuals have an extremist positive opinion that does not change. We consider that the vaccine has a certain effectiveness ω and as a consequence vaccinated nodes can be infected with probability β(1 − ω) if they are in contact with an infected neighbor. In this case, if the infection process is successful, the new infected individual changes his opinion from extremist positive to totally against the vaccine. We find that depending on the trend in the opinion of the society, which depends on r, different behaviors in the spread of the epidemic occurs. An epidemic threshold was found, in which below β* and above ω* the diseases never becomes an epidemic, and it varies with the opinion parameter r.",2017 Nov 9,"['Alvarez-Zuzek, Lucila G.', 'La Rocca, Cristian E.', 'Iglesias, José R.', 'Braunstein, Lidia A.']",PLoS One,,,True
9a9f30acc275c64c016770509f9b90eb091e272a,PMC,Seasonal recurrence of cowpox virus outbreaks in captive cheetahs (Acinonyx jubatus),http://dx.doi.org/10.1371/journal.pone.0187089,PMC5679633,29121668,CC BY,"Cowpox virus infections in captive cheetahs (Acinonyx jubatus) with high morbidity and mortality have already been reported in the UK and Russia in the 1970s. However, most of the reported cases have been singular events. Here, we report a total of five cowpox virus outbreaks in cheetahs in the same safari park in Denmark between 2010 and 2014. Nine cheetahs showed varying severity of clinical disease; two of them died (22%). All episodes occurred between August and October of the respective year. No other carnivores kept at the same institution nor the keepers taking care of the animals were clinically affected. The clinical picture of cowpox was confirmed by extensive laboratory investigations including histopathological and molecular analyses as well as cell culture isolation of a cowpox virus. High anti-orthopoxvirus antibody titers were detected in all 9 diseased cheetahs compared to seven contact cheetahs without clinical signs and 13 cheetahs not in direct contact. Additionally, whole genome sequencing from one sample of each cluster with subsequent phylogenetic analysis showed that the viruses from different outbreaks have individual sequences but clearly form a clade distinct from other cowpox viruses. However, the intra-clade distances are still larger than those usually observed within clades of one event. These findings indicate multiple and separate introductions of cowpox virus, probably from wild rodent populations, where the virus keeps circulating naturally and is only sporadically introduced into the cheetahs. Sero-positivity of voles (Arvicola amphibious) caught in zoo grounds strengthens this hypothesis. As a consequence, recommendations are given for medical and physical management of diseased cheetahs, for hygienic measures as well as for pre-shipment isolation before cheetah export from zoo grounds.",2017 Nov 9,"['Stagegaard, Julia', 'Kurth, Andreas', 'Stern, Daniel', 'Dabrowski, Piotr Wojciech', 'Pocknell, Ann', 'Nitsche, Andreas', 'Schrick, Livia']",PLoS One,,,True
8c9382eed553c5cbe1de32cd4dc4c9975250e274,PMC,A mechanistic spatio-temporal framework for modelling individual-to-individual transmission—With an application to the 2014-2015 West Africa Ebola outbreak,http://dx.doi.org/10.1371/journal.pcbi.1005798,PMC5679647,29084216,CC BY,"In recent years there has been growing availability of individual-level spatio-temporal disease data, particularly due to the use of modern communicating devices with GPS tracking functionality. These detailed data have been proven useful for inferring disease transmission to a more refined level than previously. However, there remains a lack of statistically sound frameworks to model the underlying transmission dynamic in a mechanistic manner. Such a development is particularly crucial for enabling a general epidemic predictive framework at the individual level. In this paper we propose a new statistical framework for mechanistically modelling individual-to-individual disease transmission in a landscape with heterogeneous population density. Our methodology is first tested using simulated datasets, validating our inferential machinery. The methodology is subsequently applied to data that describes a regional Ebola outbreak in Western Africa (2014-2015). Our results show that the methods are able to obtain estimates of key epidemiological parameters that are broadly consistent with the literature, while revealing a significantly shorter distance of transmission. More importantly, in contrast to existing approaches, we are able to perform a more general model prediction that takes into account the susceptible population. Finally, our results show that, given reasonable scenarios, the framework can be an effective surrogate for susceptible-explicit individual models which are often computationally challenging.",2017 Oct 30,"['Lau, Max S. Y.', 'Gibson, Gavin J.', 'Adrakey, Hola', 'McClelland, Amanda', 'Riley, Steven', 'Zelner, Jon', 'Streftaris, George', 'Funk, Sebastian', 'Metcalf, Jessica', 'Dalziel, Benjamin D.', 'Grenfell, Bryan T.']",PLoS Comput Biol,,,True
266da81290486b68fea7c553e21fa6a5d46aa6b7,PMC,A mechanistic spatio-temporal framework for modelling individual-to-individual transmission—With an application to the 2014-2015 West Africa Ebola outbreak,http://dx.doi.org/10.1371/journal.pcbi.1005798,PMC5679647,29084216,CC BY,"In recent years there has been growing availability of individual-level spatio-temporal disease data, particularly due to the use of modern communicating devices with GPS tracking functionality. These detailed data have been proven useful for inferring disease transmission to a more refined level than previously. However, there remains a lack of statistically sound frameworks to model the underlying transmission dynamic in a mechanistic manner. Such a development is particularly crucial for enabling a general epidemic predictive framework at the individual level. In this paper we propose a new statistical framework for mechanistically modelling individual-to-individual disease transmission in a landscape with heterogeneous population density. Our methodology is first tested using simulated datasets, validating our inferential machinery. The methodology is subsequently applied to data that describes a regional Ebola outbreak in Western Africa (2014-2015). Our results show that the methods are able to obtain estimates of key epidemiological parameters that are broadly consistent with the literature, while revealing a significantly shorter distance of transmission. More importantly, in contrast to existing approaches, we are able to perform a more general model prediction that takes into account the susceptible population. Finally, our results show that, given reasonable scenarios, the framework can be an effective surrogate for susceptible-explicit individual models which are often computationally challenging.",2017 Oct 30,"['Lau, Max S. Y.', 'Gibson, Gavin J.', 'Adrakey, Hola', 'McClelland, Amanda', 'Riley, Steven', 'Zelner, Jon', 'Streftaris, George', 'Funk, Sebastian', 'Metcalf, Jessica', 'Dalziel, Benjamin D.', 'Grenfell, Bryan T.']",PLoS Comput Biol,,,True
900e41d6d6ed985556b74bdf32ff59f782a53eaa,PMC,A mechanistic spatio-temporal framework for modelling individual-to-individual transmission—With an application to the 2014-2015 West Africa Ebola outbreak,http://dx.doi.org/10.1371/journal.pcbi.1005798,PMC5679647,29084216,CC BY,"In recent years there has been growing availability of individual-level spatio-temporal disease data, particularly due to the use of modern communicating devices with GPS tracking functionality. These detailed data have been proven useful for inferring disease transmission to a more refined level than previously. However, there remains a lack of statistically sound frameworks to model the underlying transmission dynamic in a mechanistic manner. Such a development is particularly crucial for enabling a general epidemic predictive framework at the individual level. In this paper we propose a new statistical framework for mechanistically modelling individual-to-individual disease transmission in a landscape with heterogeneous population density. Our methodology is first tested using simulated datasets, validating our inferential machinery. The methodology is subsequently applied to data that describes a regional Ebola outbreak in Western Africa (2014-2015). Our results show that the methods are able to obtain estimates of key epidemiological parameters that are broadly consistent with the literature, while revealing a significantly shorter distance of transmission. More importantly, in contrast to existing approaches, we are able to perform a more general model prediction that takes into account the susceptible population. Finally, our results show that, given reasonable scenarios, the framework can be an effective surrogate for susceptible-explicit individual models which are often computationally challenging.",2017 Oct 30,"['Lau, Max S. Y.', 'Gibson, Gavin J.', 'Adrakey, Hola', 'McClelland, Amanda', 'Riley, Steven', 'Zelner, Jon', 'Streftaris, George', 'Funk, Sebastian', 'Metcalf, Jessica', 'Dalziel, Benjamin D.', 'Grenfell, Bryan T.']",PLoS Comput Biol,,,False
8eaeb94e7c33ba2239a50baf85aca20a113f69b0,PMC,A mechanistic spatio-temporal framework for modelling individual-to-individual transmission—With an application to the 2014-2015 West Africa Ebola outbreak,http://dx.doi.org/10.1371/journal.pcbi.1005798,PMC5679647,29084216,CC BY,"In recent years there has been growing availability of individual-level spatio-temporal disease data, particularly due to the use of modern communicating devices with GPS tracking functionality. These detailed data have been proven useful for inferring disease transmission to a more refined level than previously. However, there remains a lack of statistically sound frameworks to model the underlying transmission dynamic in a mechanistic manner. Such a development is particularly crucial for enabling a general epidemic predictive framework at the individual level. In this paper we propose a new statistical framework for mechanistically modelling individual-to-individual disease transmission in a landscape with heterogeneous population density. Our methodology is first tested using simulated datasets, validating our inferential machinery. The methodology is subsequently applied to data that describes a regional Ebola outbreak in Western Africa (2014-2015). Our results show that the methods are able to obtain estimates of key epidemiological parameters that are broadly consistent with the literature, while revealing a significantly shorter distance of transmission. More importantly, in contrast to existing approaches, we are able to perform a more general model prediction that takes into account the susceptible population. Finally, our results show that, given reasonable scenarios, the framework can be an effective surrogate for susceptible-explicit individual models which are often computationally challenging.",2017 Oct 30,"['Lau, Max S. Y.', 'Gibson, Gavin J.', 'Adrakey, Hola', 'McClelland, Amanda', 'Riley, Steven', 'Zelner, Jon', 'Streftaris, George', 'Funk, Sebastian', 'Metcalf, Jessica', 'Dalziel, Benjamin D.', 'Grenfell, Bryan T.']",PLoS Comput Biol,,,False
0d4823662057bf29b7db84d4c69053f9f0d2ef8d,PMC,A mechanistic spatio-temporal framework for modelling individual-to-individual transmission—With an application to the 2014-2015 West Africa Ebola outbreak,http://dx.doi.org/10.1371/journal.pcbi.1005798,PMC5679647,29084216,CC BY,"In recent years there has been growing availability of individual-level spatio-temporal disease data, particularly due to the use of modern communicating devices with GPS tracking functionality. These detailed data have been proven useful for inferring disease transmission to a more refined level than previously. However, there remains a lack of statistically sound frameworks to model the underlying transmission dynamic in a mechanistic manner. Such a development is particularly crucial for enabling a general epidemic predictive framework at the individual level. In this paper we propose a new statistical framework for mechanistically modelling individual-to-individual disease transmission in a landscape with heterogeneous population density. Our methodology is first tested using simulated datasets, validating our inferential machinery. The methodology is subsequently applied to data that describes a regional Ebola outbreak in Western Africa (2014-2015). Our results show that the methods are able to obtain estimates of key epidemiological parameters that are broadly consistent with the literature, while revealing a significantly shorter distance of transmission. More importantly, in contrast to existing approaches, we are able to perform a more general model prediction that takes into account the susceptible population. Finally, our results show that, given reasonable scenarios, the framework can be an effective surrogate for susceptible-explicit individual models which are often computationally challenging.",2017 Oct 30,"['Lau, Max S. Y.', 'Gibson, Gavin J.', 'Adrakey, Hola', 'McClelland, Amanda', 'Riley, Steven', 'Zelner, Jon', 'Streftaris, George', 'Funk, Sebastian', 'Metcalf, Jessica', 'Dalziel, Benjamin D.', 'Grenfell, Bryan T.']",PLoS Comput Biol,,,False
977443e0da4b96f5b6f6666d870a8340ebe70678,PMC,A mechanistic spatio-temporal framework for modelling individual-to-individual transmission—With an application to the 2014-2015 West Africa Ebola outbreak,http://dx.doi.org/10.1371/journal.pcbi.1005798,PMC5679647,29084216,CC BY,"In recent years there has been growing availability of individual-level spatio-temporal disease data, particularly due to the use of modern communicating devices with GPS tracking functionality. These detailed data have been proven useful for inferring disease transmission to a more refined level than previously. However, there remains a lack of statistically sound frameworks to model the underlying transmission dynamic in a mechanistic manner. Such a development is particularly crucial for enabling a general epidemic predictive framework at the individual level. In this paper we propose a new statistical framework for mechanistically modelling individual-to-individual disease transmission in a landscape with heterogeneous population density. Our methodology is first tested using simulated datasets, validating our inferential machinery. The methodology is subsequently applied to data that describes a regional Ebola outbreak in Western Africa (2014-2015). Our results show that the methods are able to obtain estimates of key epidemiological parameters that are broadly consistent with the literature, while revealing a significantly shorter distance of transmission. More importantly, in contrast to existing approaches, we are able to perform a more general model prediction that takes into account the susceptible population. Finally, our results show that, given reasonable scenarios, the framework can be an effective surrogate for susceptible-explicit individual models which are often computationally challenging.",2017 Oct 30,"['Lau, Max S. Y.', 'Gibson, Gavin J.', 'Adrakey, Hola', 'McClelland, Amanda', 'Riley, Steven', 'Zelner, Jon', 'Streftaris, George', 'Funk, Sebastian', 'Metcalf, Jessica', 'Dalziel, Benjamin D.', 'Grenfell, Bryan T.']",PLoS Comput Biol,,,False
77ee6f11d8a0a54182e837f5c19ffedcf3d07e01,PMC,"Complete Genome Sequence of a Novel Strain of Infectious Bronchitis Virus, Isolated from Chickens in China in 2016",http://dx.doi.org/10.1128/genomeA.01277-17,PMC5679815,29122882,CC BY,"An avian infectious bronchitis virus (IBV) was detected from trachea swabs of chickens in Hubei province, China, in 2016. The complete genome of the IBV strain, CK/CH/HB/2016, was characterized and analyzed to better understand IBV epidemiology in China.",2017 Nov 9,"['Li, Ting-Ting', 'Li, Jin-Yan', 'Huang, Tao', 'Ge, Xing-Yi']",Genome Announc,,,False
77e7d43cae5e05f9a6937b0c3326871a41ea20cd,PMC,Multipartite viruses: adaptive trick or evolutionary treat?,http://dx.doi.org/10.1038/s41540-017-0035-y,PMC5680193,29263796,CC BY,"Multipartitism counts amongst the weirdest lifestyles found in the virosphere. Multipartite viruses have genomes segmented in pieces enclosed in different capsids that are independently transmitted. Since all segments have to meet in the host for complementation and completion of the viral cycle, multipartite viruses are bound to fight the loss of genomic information. While this is an obvious disadvantage of this strategy, no consensus on its actual advantages has been reached. In this review we present an exhaustive summary of all multipartite viruses described to date. Based on evidence, we discuss possible mechanistic and evolutionary origins of different groups, as well as their mutual relationships. We argue that the ubiquitous interactions of viruses with other unrelated viruses and with subviral elements might be regarded as a plausible first step towards multipartitism. In agreement with the view of the Virosphere as a deeply entangled network of gene sharing, we contend that the power of multipartitism relies on its dynamical and opportunistic nature, because it enables immediate adaptive responses to environmental changes. As such, perhaps the reasons for its success should be shought in multipartitism itself as an adaptive mechanism, to which its evolutionarily short-lived products (that is, the extant ensemble of multipartite viral species) are subordinated. We close by discussing how our understanding of multipartitism would improve by using concepts and tools from systems biology.",2017 Nov 9,"['Lucía-Sanz, Adriana', 'Manrubia, Susanna']",NPJ Syst Biol Appl,,,True
3a2f058d14f4b6db1e7191a2ed2634d5c5699455,PMC,Essential role of HCMV deubiquitinase in promoting oncogenesis by targeting anti-viral innate immune signaling pathways,http://dx.doi.org/10.1038/cddis.2017.461,PMC5680583,28981114,CC BY,"Cancer is a multifactorial disease and virus-mediated carcinogenesis is one of the crucial factors, which is poorly understood. Human cytomegalovirus (HCMV) is a herpesvirus and its components have been evidenced to be associated with cancer of different tissue origin. However, its role in cancer remains unknown. Here, we identified a conserved herpesviral tegument protein known as pUL48 of HCMV, encoding deubiquitinase enzyme, as having a key role in carcinogenesis. We show using deubiquitinase sufficient- and deficient-HCMV that HCMV deubiquitinase is a key in inducing enhanced cellular metabolic activity through upregulation of several anti-apoptotic genes and downregulation of several pro-apoptotic genes expression. Furthermore, HCMV deubiquitinase acquires pro-tumor functions by inhibiting PRR-mediated type I interferon via deubiquitination of TRAF6, TRAF3, IRAK1, IRF7 and STING. Taken together, our results suggest that HCMV infection may promote oncogenesis by inhibiting innate immunity of the host.",2017 Oct 5,"['Kumari, Puja', 'Saha, Irene', 'Narayanan, Athira', 'Narayanan, Sathish', 'Takaoka, Akinori', 'Kumar, Nachimuthu Senthil', 'Tailor, Prafullakumar', 'Kumar, Himanshu']",Cell Death Dis,,,True
84efaac896e551763256fd4d16e56a99b416c175,PMC,"Ancient oncogenesis, infection and human evolution",http://dx.doi.org/10.1111/eva.12497,PMC5680625,29151852,CC BY,"The recent discovery that malignant neoplastic lesions date back nearly 2 million years ago not only highlights the antiquity of cancer in the human lineage, but also provides remarkable insight into ancestral hominin disease pathology. Using these Early Pleistocene examples as a point of departure, we emphasize the prominent role of viral and bacterial pathogens in oncogenesis and evaluate the impact of pathogens on human evolutionary processes in Africa. In the Shakespearean vernacular “what's past is prologue,” we highlight the significance of novel information derived from ancient pathogenic DNA. In particular, and given the temporal depth of human occupation in sub‐Saharan Africa, it is emphasized that the region is ideally positioned to play a strategic role in the discovery of ancient pathogenic drivers of not only human mortality, but also human evolution. Ancient African pathogen genome data can provide novel revelations concerning human‐pathogen coevolutionary processes, and such knowledge is essential for forecasting the ways in which emerging zoonotic and increasingly transmissible diseases might influence human demography and longevity in the future.",2017 Jul 11,"['Rifkin, Riaan F.', 'Potgieter, Marnie', 'Ramond, Jean‐Baptiste', 'Cowan, Don A.']",Evol Appl,,,True
424f52f1d390c220aaaea5efa3e59696a2e903f3,PMC,"Association of IFITM3 rs12252 polymorphisms, BMI, diabetes, and hypercholesterolemia with mild flu in an Iranian population",http://dx.doi.org/10.1186/s12985-017-0884-4,PMC5680824,29121968,CC BY,"BACKGROUND: IFITM3 has been suggested to be associated with infection in some ethnic groups. Diabetes and hypercholesterolemia are also important clinical conditions that can predispose individuals to infection. The aim of this study was to investigate the association of rs12252 C polymorphism, BMI, diabetes, and hypercholesterolemia with mild flu in an Iranian population. METHODS: We conducted a case-control study, including 79 mild flu and 125 flu-negative individuals attending primary care centers of three provinces of Iran (i.e, Markazi, Semnan, and Zanjan). Pharyngeal swab specimens were collected from all participants, and were subjected to RNA and DNA extractions for Real-time PCR and PCR tests. All PCR products were then sequenced to find T/C polymorphisms in the rs12252 region. Data on demographic, anthropometric, and clinical variables were collected from participants’ medical records available in the primary care centers. The data was analyzed using DNASIS (v. 2.5) and Stata (v.11) software. RESULTS: All participants were of Fars ethnic background. The allele frequency for rs12252-C was found to be 9.49% among cases and 2.40% among controls. Carriers of the rs12252 C allele (CT + CC genotypes) showed 5.92 folds increase in the risk of mild flu comparing to the T allele homozygotes (P value: 0.007). We also found a significant positive association between rs12252 C allele heterozygote and mild flu (OR: 7.62, P value: 0.008), but not in C allele homozygote group (OR: 2.71, P value: 0.406). Similarly, we did not find a significant association between mild flu and BMI (OR: 1.06, P value: 0.087), diabetes (OR: 0.61, P value: 0.392), and hypercholesterolemia (OR: 0.50, P value: 0.393) in multivariable logistic regression. CONCLUSIONS: This is the first study evaluating the association between rs12252 polymorphisms, diabetes, hypercholesterolemia, and BMI and susceptibility to mild flu in an Iranian population. Our results suggest a significant positive association between mild flu and rs12252 C allele heterozygous and carriage. Future replication of the strong association observed here between rs12252 C allele carriage and mild flu might candidate this polymorphism as a genetic marker for early screening of susceptibility to mild flu. Lack of significant association between C allele homozygous and mild flu, observed in this study, might be the result of small sample size in this group. TRIAL REGISTRATION: IR.PII.REC.1395.3. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-017-0884-4) contains supplementary material, which is available to authorized users.",2017 Nov 9,"['Mehrbod, Parvaneh', 'Eybpoosh, Sana', 'Fotouhi, Fatemeh', 'Shokouhi Targhi, Hadiseh', 'Mazaheri, Vahideh', 'Farahmand, Behrokh']",Virol J,,,True
7c64dd916107c4834e94b209c7aadc61be6d7c3f,PMC,"No MERS-CoV but positive influenza viruses in returning Hajj pilgrims, China, 2013–2015",http://dx.doi.org/10.1186/s12879-017-2791-0,PMC5681762,29126397,CC BY,"BACKGROUND: There is global health concern that the mass movement of pilgrims to and from Mecca annually could contribute to the international spread of Middle East Respiratory Syndrome Coronavirus (MERS-CoV). In China, about 11,000 Muslim pilgrims participate in the Hajj gathering in Mecca annually. This is the first report of MERS-CoV and respiratory virus molecular screening of returning pilgrims at points of entry in China from 2013 to 2015. METHODS AND RESULTS: A total of 847 returning Hajj pilgrims participated in this study. The test results indicated that of the travelers, 34 tested positive for influenza A virus, 14 for influenza B virus, 4 for metapneumo virus, 2 for respiratory syncytial virus, and 3 for human coronavirus. There was a significant difference in the rates of positive and negative influenza virus tests between Hajj pilgrims with symptoms and those without. The detection rates of influenza virus were not significantly different among the three years studied, at 5.3, 6.0 and 6.3% for 2013, 2014 and 2015, respectively. DISCUSSION AND CONCLUSION: The MERS-CoV and respiratory viruses detection results at points of entry in China from 2013 to 2015 indicated that there were no MERS-CoV infection but a 5.7% positive influenza viruses in returning Chinese pilgrims.",2017 Nov 10,"['Ma, Xuezheng', 'Liu, Fang', 'Liu, Lijuan', 'Zhang, Liping', 'Lu, Mingzhu', 'Abudukadeer, Abuduzhayier', 'Wang, Lingbing', 'Tian, Feng', 'Zhen, Wei', 'Yang, Pengfei', 'Hu, Kongxin']",BMC Infect Dis,,,True
38d6c3ecce86e079e55dcb9a1b33f2a239b3ba81,PMC,Public health concerns of highly pathogenic avian influenza H5N1 endemicity in Africa,http://dx.doi.org/10.14202/vetworld.2017.1194-1204,PMC5682264,29184365,CC BY,"Highly pathogenic avian influenza virus (HPAIV) H5N1 was first officially reported in Africa in 2006; thereafter this virus has spread rapidly from Nigeria to 11 other African countries. This study was aimed at utilizing data from confirmed laboratory reports to carry out a qualitative evaluation of the factors responsible for HPAI H5N1 persistence in Africa and the public health implications; and to suggest appropriate control measures. Relevant publications were sought from data banks and repositories of FAO, OIE, WHO, and Google scholars. Substantiated data on HPAI H5N1 outbreaks in poultry in Africa and in humans across the world were mined. HPAI H5N1 affects poultry and human populations, with Egypt having highest human cases (346) globally. Nigeria had a reinfection from 2014 to 2015, with outbreaks in Côte d’Ivoire, Ghana, Niger, Nigeria, and Burkina Faso throughout 2016 unabated. The persistence of this virus in Africa is attributed to the survivability of HPAIV, ability to evolve other subtypes through genetic reassortment, poor biosecurity compliance at the live bird markets and poultry farms, husbandry methods and multispecies livestock farming, poultry vaccinations, and continuous shedding of HPAIV, transboundary transmission of HPAIV through poultry trades; and transcontinental migratory birds. There is, therefore, the need for African nations to realistically reassess their status, through regular surveillance and be transparent with HPAI H5N1 outbreak data. Also, it is important to have an understanding of HPAIV migration dynamics which will be helpful in epidemiological modeling, disease prevention, control and eradication measures.",2017 Oct 8,"['Fasanmi, Olubunmi Gabriel', 'Odetokun, Ismail Ayoade', 'Balogun, Fatima Adeola', 'Fasina, Folorunso Oludayo']",Vet World,,,True
04bc03c90437934a75fc6fdc228817234ef84c3a,PMC,A New Immunosuppressive Molecule Emodin Induces both CD4(+)FoxP3(+) and CD8(+)CD122(+) Regulatory T Cells and Suppresses Murine Allograft Rejection,http://dx.doi.org/10.3389/fimmu.2017.01519,PMC5682309,29167674,CC BY,"Due to vigorous alloimmunity, an allograft is usually rejected without any conventional immunosuppressive treatment. However, continuous global immunosuppression may cause severe side effects, including tumors and infections. Mounting evidence has shown that cyclosporine (CsA), a common immunosuppressant used in clinic, impedes allograft tolerance by dampening regulatory T cells (Tregs), although it inhibits allograft rejection at the same time. Therefore, it is necessary to seek an alternative immunosuppressive drug that spares Tregs with high efficiency in suppression but low toxicity. In this study, we investigated the capacity of emodin, an anthraquinone molecule originally extracted from certain natural plants, to prolong transplant survival in a mouse model and explored the cellular and molecular mechanisms underlying its action. We found that emodin significantly extended skin allograft survival and hindered CD3(+) T cell infiltration in the allograft, accompanied by an increase in CD4(+)Foxp3(+) and CD8(+)CD122(+) Treg frequencies and numbers but a reduction in effector CD8(+)CD44(high)CD62L(low) T cells in recipient mice. Emodin also inhibited effector CD8(+) T cells proliferation in vivo. However, CD4(+)CD25(+), but not CD8(+)CD122(+), Tregs derived from emodin-treated recipients were more potent in suppression of allograft rejection than those isolated from control recipients, suggesting that emodin also enhances the suppressive function of CD4(+)CD25(+) Tregs. Interestingly, depleting CD25(+) Tregs largely reversed skin allograft survival prolonged by emodin while depleting CD122(+) Tregs only partially abrogated the same allograft survival. Furthermore, we found that emodin hindered dendritic cell (DC) maturation and reduced alloantibody production posttransplantation. Finally, we demonstrated that emodin inhibited in vitro proliferation of T cells and blocked their mTOR signaling as well. Therefore, emodin may be a novel mTOR inhibitor that suppresses alloimmunity by inducing both CD4(+)FoxP3(+) and CD8(+)CD122(+) Tregs, suppressing alloantibody production, and hindering DC maturation. Thus, emodin is a newly emerging immunosuppressant and could be utilized in clinical transplantation in the future.",2017 Nov 8,"['Qiu, Feifei', 'Liu, Huazhen', 'Liang, Chun-Ling', 'Nie, Golay D.', 'Dai, Zhenhua']",Front Immunol,,,True
2532e472bef55445067d0fa7173cc00139eba7cd,PMC,A New Immunosuppressive Molecule Emodin Induces both CD4(+)FoxP3(+) and CD8(+)CD122(+) Regulatory T Cells and Suppresses Murine Allograft Rejection,http://dx.doi.org/10.3389/fimmu.2017.01519,PMC5682309,29167674,CC BY,"Due to vigorous alloimmunity, an allograft is usually rejected without any conventional immunosuppressive treatment. However, continuous global immunosuppression may cause severe side effects, including tumors and infections. Mounting evidence has shown that cyclosporine (CsA), a common immunosuppressant used in clinic, impedes allograft tolerance by dampening regulatory T cells (Tregs), although it inhibits allograft rejection at the same time. Therefore, it is necessary to seek an alternative immunosuppressive drug that spares Tregs with high efficiency in suppression but low toxicity. In this study, we investigated the capacity of emodin, an anthraquinone molecule originally extracted from certain natural plants, to prolong transplant survival in a mouse model and explored the cellular and molecular mechanisms underlying its action. We found that emodin significantly extended skin allograft survival and hindered CD3(+) T cell infiltration in the allograft, accompanied by an increase in CD4(+)Foxp3(+) and CD8(+)CD122(+) Treg frequencies and numbers but a reduction in effector CD8(+)CD44(high)CD62L(low) T cells in recipient mice. Emodin also inhibited effector CD8(+) T cells proliferation in vivo. However, CD4(+)CD25(+), but not CD8(+)CD122(+), Tregs derived from emodin-treated recipients were more potent in suppression of allograft rejection than those isolated from control recipients, suggesting that emodin also enhances the suppressive function of CD4(+)CD25(+) Tregs. Interestingly, depleting CD25(+) Tregs largely reversed skin allograft survival prolonged by emodin while depleting CD122(+) Tregs only partially abrogated the same allograft survival. Furthermore, we found that emodin hindered dendritic cell (DC) maturation and reduced alloantibody production posttransplantation. Finally, we demonstrated that emodin inhibited in vitro proliferation of T cells and blocked their mTOR signaling as well. Therefore, emodin may be a novel mTOR inhibitor that suppresses alloimmunity by inducing both CD4(+)FoxP3(+) and CD8(+)CD122(+) Tregs, suppressing alloantibody production, and hindering DC maturation. Thus, emodin is a newly emerging immunosuppressant and could be utilized in clinical transplantation in the future.",2017 Nov 8,"['Qiu, Feifei', 'Liu, Huazhen', 'Liang, Chun-Ling', 'Nie, Golay D.', 'Dai, Zhenhua']",Front Immunol,,,False
568dd96f69f07844df6ac84d80188eaa94c7b4c5,PMC,"Qatar steps up to Global Health security: a reflection on the joint external evaluation, 2016",http://dx.doi.org/10.1186/s41256-017-0050-y,PMC5683357,29202098,CC BY,"Since the commencement of the International Health Regulations in 2007, global public health security has been faced with numerous emerging and ongoing events. Moreover, the Joint External Evaluation is a voluntary tool developed in compliance with the Global Health Security Agenda that represents the high responsibility of international health community towards the increased incidence of emerging and re-emerging diseases. Against this background, between 29th May and 2nd June 2016, a team of World Health Organization consultants arrived to the State of Qatar to assess, in collaboration with national experts, the country’s capacity to prevent, detect, and rapidly respond to threats of public health aspect. They identified areas of strength, weakness, and recommendations for improving national health security of Qatar in anticipation of the 2022 FIFA World Cup event. Qatar has demonstrated a leading role in the region through its commitment to International Health Regulations (2005) and population health. Similarly, the Qatar was the first Arab state and seventh volunteering country globally to undergo the Joint External evaluation process. In this review, we highlighted Qatar’s achievements and shortcomings of International Health Regulations’ core capacities to inform healthcare professionals and the scientific community about the country’s contribution toward global health security.",2017 Oct 18,"['Bala, Mohamed Osman', 'Chehab, Mohamad Abdelhalim', 'Selim, Nagah Abdel Aziz']",Glob Health Res Policy,,,True
659220e080e623e34f3efe2ce84e63fb2cefdd8e,PMC,Phylodynamic applications in 21(st) century global infectious disease research,http://dx.doi.org/10.1186/s41256-017-0034-y,PMC5683535,29202081,CC BY,"BACKGROUND: Phylodynamics, the study of the interaction between epidemiological and pathogen evolutionary processes within and among populations, was originally defined in the context of rapidly evolving viruses and used to characterize transmission dynamics. The concept of phylodynamics has evolved since the early 21(st) century, extending its reach to slower-evolving pathogens, including bacteria and fungi, and to the identification of influential factors in disease spread and pathogen population dynamics. RESULTS: The phylodynamic approach has now become a fundamental building block for the development of comparative phylogenetic tools capable of incorporating epidemiological surveillance data with molecular sequences into a single statistical framework. These innovative tools have greatly enhanced scientific investigations of the temporal and geographical origins, evolutionary history, and ecological risk factors associated with the growth and spread of viruses such as human immunodeficiency virus (HIV), Zika, and dengue and bacteria such as Methicillin-resistant Staphylococcus aureus. CONCLUSIONS: Capitalizing on an extensive review of the literature, we discuss the evolution of the field of infectious disease epidemiology and recent accomplishments, highlighting the advancements in phylodynamics, as well as the challenges and limitations currently facing researchers studying emerging pathogen epidemics across the globe. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s41256-017-0034-y) contains supplementary material, which is available to authorized users.",2017 May 8,"['Rife, Brittany D', 'Mavian, Carla', 'Chen, Xinguang', 'Ciccozzi, Massimo', 'Salemi, Marco', 'Min, Jae', 'Prosperi, Mattia CF']",Glob Health Res Policy,,,True
1eadeab29c774bb8b5935c5ce5d741855a8080a5,PMC,The role of risk perception in willingness to respond to the 2014–2016 West African Ebola outbreak: a qualitative study of international health care workers.,http://dx.doi.org/10.1186/s41256-017-0042-y,PMC5683558,29202089,CC BY,"BACKGROUND: The 2014–2016 West Africa Ebola Virus Disease (EVD) outbreak was an unprecedented public health event, and in addition to claiming over 11,000 lives, it resulted in the deaths of more healthcare workers than any outbreak in recent history. While a cadre of willing and able health workers is essential for an effective epidemic response, health workforce capacity in times of crisis may be significantly impacted by how risks are perceived by health staff. This study aimed to explore how risk perceptions influenced healthcare workers’ willingness to respond during this outbreak. METHODS: Through in-depth interviews with 11 front-line international health care workers who chose to respond to the West Africa outbreak, this qualitative study explores how perceptions of risk developed and subsequently mediated the decision to respond to the outbreak. Data was thematically organized using NVivo 10. RESULTS: We found that numerous individual and social-level factors played a role in modifying risk perception in health workers. Institutional trust emerged as a key risk attenuator, as did past experience, self-efficacy, duty of care, humanitarian ethos, and cognitive heuristics. Feelings of risk were amplified by infections of co-workers, and risk perceptions of family members and the public, which were mainly informed by media reports, also hampered willingness to respond in some cases. CONCLUSIONS: Understanding the risk perceptions of health workers, institutions, and the public, while complex and interdependent, are each crucial to understand for an effective public health response to epidemics, and as such should be taken into consideration in future program planning and research.",2017 Aug 7,"['Gee, Stephanie', 'Skovdal, Morten']",Glob Health Res Policy,,,True
de34db0d2ca85142ffadf43e8a6abec285608f9e,PMC,Avian infectious bronchitis virus disrupts the melanoma differentiation associated gene 5 (MDA5) signaling pathway by cleavage of the adaptor protein MAVS,http://dx.doi.org/10.1186/s12917-017-1253-7,PMC5683607,29132350,CC BY,"BACKGROUND: Melanoma differentiation associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I) selectively sense cytoplasmic viral RNA to induce an antiviral immune response. Infectious bronchitis virus (IBV) is one of the most important infectious agents in chickens, and in chicken cells, it can be recognized by MDA5 to activate interferon production. RIG-I is considered to be absent in chickens. However, the absence of RIG-I in chickens raises the question of whether this protein influences the antiviral immune response against IBV infection. RESULTS: Here, we showed that chicken cells transfected with domestic goose RIG-I (dgRIG-I) exhibited increased IFN-β activity after IBV infection. We also found that IBV can cleave MAVS, an adaptor protein downstream of RIG-I and MDA5 that acts as a platform for antiviral innate immunity at an early stage of infection. CONCLUSIONS: Although chicken MDA5 (chMDA5) is functionally active during IBV infection, the absence of RIG-I may increase the susceptibility of chickens to IBV infection, and IBV may disrupt the activation of the host antiviral response through the cleavage of MAVS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi: 10.1186/s12917-017-1253-7) contains supplementary material, which is available to authorized users.",2017 Nov 13,"['Yu, Liping', 'Zhang, Xiaorong', 'Wu, Tianqi', 'Su, Jin', 'Wang, Yuyang', 'Wang, Yuexin', 'Ruan, Baoyang', 'Niu, Xiaosai', 'Wu, Yantao']",BMC Vet Res,,,True
87773b968fb19ed46a80e0d44986bb965fa87cf6,PMC,Comparative Diagnostic Performance of the Granulocyte and Neutrophil Counts,http://dx.doi.org/10.1016/j.plabm.2017.10.001,PMC5683674,29159255,CC BY,"OBJECTIVES: Use of point-of-care testing is increasing, however many haematology analysers can only determine granulocyte count without further differentiation into neutrophils, eosinophils and basophils. Since the diagnosis of life-threatening neutropenia in cancer patients requires a distinct neutrophil count, this study aimed to determine the comparative performance between the neutrophil and granulocyte count. DESIGN AND METHODS: A database of 508 646 venous full blood count results measured on a laboratory reference analyser was mined from a large oncology unit. The relationship between granulocyte and neutrophil counts was assessed. Multinomial logistic regression was used to classify results into neutropenia grades using an equivalent granulocyte count. RESULTS: Granulocyte to neutrophil count correlation was 0.997. The accuracy for classification into neutropenia grades using the derived equivalent granulocyte count ranges was 96.4%. Identification of results with a neutrophil count <1.5×10(9) cells/L using an equivalent granulocyte count of <1.69×10(9) cells/L resulted in sensitivity, specificity, positive and negative predictive values of 98.0%, 99.5%, 97.8% and 99.5%, respectively. CONCLUSIONS: These results describe the relationship between granulocyte and neutrophil counts, measured on a laboratory analyser, in a large population of patients with malignancies and receiving anti-cancer therapies. However, this relationship must be established using a point of care testing system with a three-part differential count before considering the possibility that a granulocyte count can guide clinical decisions in the absence of a definitive neutrophil count, to reduce the frequency and severity of neutropenic complications in patients receiving cancer treatments.",2017 Oct 4,"['Pether, Nicola S.', 'Brothwood, Jessica L.', 'van Berkel, Cornelis', 'Dunwoodie, Elaine H.', 'Blake, Robert L.', 'Price, Christopher P.', 'Jones, Richard G.', 'Baker, Karl S.', 'Hall, Geoff']",Pract Lab Med,,,False
99c5eece9bcc42ce3056f49db1fe5c164af99834,PMC,"Status, quality and specific needs of Zika virus (ZIKV) diagnostic capacity and capability in National Reference Laboratories for arboviruses in 30 EU/EEA countries, May 2016",http://dx.doi.org/10.2807/1560-7917.ES.2017.22.36.30609,PMC5685210,28920574,CC BY,"With international travel, Zika virus (ZIKV) is introduced to Europe regularly. A country's ability to robustly detect ZIKV introduction and local transmission is important to minimise the risk for a ZIKV outbreak. Therefore, sufficient expertise and diagnostic capacity and capability are required in European laboratories. To assess the capacity, quality, operational specifics (guidelines and algorithms), technical and interpretation issues and other possible difficulties that were related to ZIKV diagnostics in European countries, a questionnaire was conducted among national reference laboratories in 30 countries in the European Union/European Economic Area (EU/EEA) in May 2016. While the coverage and capacity of ZIKV diagnostics in the EU/EEA national reference laboratories were found to be adequate, the assessment of the quality and needs indicated several crucial points of improvement that will need support at national and EU/EEA level to improve ZIKV preparedness, response and EU/EEA ZIKV surveillance activities.",2017 Sep 7,"['Mögling, Ramona', 'Zeller, Hervé', 'Revez, Joana', 'Koopmans, Marion', None, 'Reusken, Chantal']",Euro Surveill,,,True
904be1b54f8b7ce0eba0f553eedc70dbb78f138d,PMC,Internal quality assurance in diagnostic microbiology: A simple approach for insightful data,http://dx.doi.org/10.1371/journal.pone.0187263,PMC5685576,29135992,CC BY,"Given the importance of microbiology results on patient care, high quality standards are expected. Internal quality assurance (IQA) could mitigate the limitations of internal quality control, competency assessment and external quality assurance, adding a longitudinal insight, including pre- and post-analytical steps. Here, we implemented an IQA program in our clinical microbiology facilities with blind resubmission of routine samples during 22 months. One-hundred-and-twenty-one out of 123 (98.4%) serological analyses and 112 out of 122 (91.8%) molecular analyses were concordant. Among the discordances in molecular biology analyses, 6 results were low positive samples that turned out negative, likely due to stochastic repartition of nucleic acids. Moreover, one identified retranscription error led us to implement automated results transmission from the Applied Biosystems instruments to the laboratory information system (LIS). Regarding Gram stain microscopy, 560 out of 745 (75.2%) of compared parameters were concordant. As many as 67 out of 84 (79.8%) pairs of culture results were similar, including 16 sterile pairs, 27 having identical identification or description and semi-quantification and 24 only showing variations in semi-quantification with identical description or identification of colonies. Seventeen pairs had diverging identification or description of colonies. Culture was twice only done for one member of the pairs. Regarding antibiotic susceptibility testing, a major discrepancy was observed in 5 out of 48 results (10.4%). In conclusion, serological tests were highly reproducible. Molecular diagnosis also revealed to be robust except when the amounts of nucleic acids present in the sample were close to the limits of detection. Conventional microbiology was less robust with major discrepancies reaching 39.5% of the samples for microscopy. Similarly, culture and antibiotic susceptibility testing were prone to discrepancies. This work was ground for reconsidering multiples aspects of our practices and demonstrates the importance of IQA to complete the other quality management procedures.",2017 Nov 14,"['Scherz, Valentin', 'Durussel, Christian', 'Greub, Gilbert']",PLoS One,,,True
c41e25d8e7fa94ffa409d6574d4e65f5646a562f,PMC,"ABMA, a small molecule that inhibits intracellular toxins and pathogens by interfering with late endosomal compartments",http://dx.doi.org/10.1038/s41598-017-15466-7,PMC5686106,29138439,CC BY,"Intracellular pathogenic microorganisms and toxins exploit host cell mechanisms to enter, exert their deleterious effects as well as hijack host nutrition for their development. A potential approach to treat multiple pathogen infections and that should not induce drug resistance is the use of small molecules that target host components. We identified the compound 1-adamantyl (5-bromo-2-methoxybenzyl) amine (ABMA) from a cell-based high throughput screening for its capacity to protect human cells and mice against ricin toxin without toxicity. This compound efficiently protects cells against various toxins and pathogens including viruses, intracellular bacteria and parasite. ABMA provokes Rab7-positive late endosomal compartment accumulation in mammalian cells without affecting other organelles (early endosomes, lysosomes, the Golgi apparatus, the endoplasmic reticulum or the nucleus). As the mechanism of action of ABMA is restricted to host-endosomal compartments, it reduces cell infection by pathogens that depend on this pathway to invade cells. ABMA may represent a novel class of broad-spectrum compounds with therapeutic potential against diverse severe infectious diseases.",2017 Nov 14,"['Wu, Yu', 'Pons, Valérie', 'Goudet, Amélie', 'Panigai, Laetitia', 'Fischer, Annette', 'Herweg, Jo-Ana', 'Kali, Sabrina', 'Davey, Robert A.', 'Laporte, Jérôme', 'Bouclier, Céline', 'Yousfi, Rahima', 'Aubenque, Céline', 'Merer, Goulven', 'Gobbo, Emilie', 'Lopez, Roman', 'Gillet, Cynthia', 'Cojean, Sandrine', 'Popoff, Michel R.', 'Clayette, Pascal', 'Le Grand, Roger', 'Boulogne, Claire', 'Tordo, Noël', 'Lemichez, Emmanuel', 'Loiseau, Philippe M.', 'Rudel, Thomas', 'Sauvaire, Didier', 'Cintrat, Jean-Christophe', 'Gillet, Daniel', 'Barbier, Julien']",Sci Rep,,,False
ff026fb53971d5bfa70c0b9b017d011cc7deee0e,PMC,"ABMA, a small molecule that inhibits intracellular toxins and pathogens by interfering with late endosomal compartments",http://dx.doi.org/10.1038/s41598-017-15466-7,PMC5686106,29138439,CC BY,"Intracellular pathogenic microorganisms and toxins exploit host cell mechanisms to enter, exert their deleterious effects as well as hijack host nutrition for their development. A potential approach to treat multiple pathogen infections and that should not induce drug resistance is the use of small molecules that target host components. We identified the compound 1-adamantyl (5-bromo-2-methoxybenzyl) amine (ABMA) from a cell-based high throughput screening for its capacity to protect human cells and mice against ricin toxin without toxicity. This compound efficiently protects cells against various toxins and pathogens including viruses, intracellular bacteria and parasite. ABMA provokes Rab7-positive late endosomal compartment accumulation in mammalian cells without affecting other organelles (early endosomes, lysosomes, the Golgi apparatus, the endoplasmic reticulum or the nucleus). As the mechanism of action of ABMA is restricted to host-endosomal compartments, it reduces cell infection by pathogens that depend on this pathway to invade cells. ABMA may represent a novel class of broad-spectrum compounds with therapeutic potential against diverse severe infectious diseases.",2017 Nov 14,"['Wu, Yu', 'Pons, Valérie', 'Goudet, Amélie', 'Panigai, Laetitia', 'Fischer, Annette', 'Herweg, Jo-Ana', 'Kali, Sabrina', 'Davey, Robert A.', 'Laporte, Jérôme', 'Bouclier, Céline', 'Yousfi, Rahima', 'Aubenque, Céline', 'Merer, Goulven', 'Gobbo, Emilie', 'Lopez, Roman', 'Gillet, Cynthia', 'Cojean, Sandrine', 'Popoff, Michel R.', 'Clayette, Pascal', 'Le Grand, Roger', 'Boulogne, Claire', 'Tordo, Noël', 'Lemichez, Emmanuel', 'Loiseau, Philippe M.', 'Rudel, Thomas', 'Sauvaire, Didier', 'Cintrat, Jean-Christophe', 'Gillet, Daniel', 'Barbier, Julien']",Sci Rep,,,True
8b67993220966ebef79688b594d852e4da9bbadb,PMC,Induction of Antiviral Immune Response through Recognition of the Repeating Subunit Pattern of Viral Capsids Is Toll-Like Receptor 2 Dependent,http://dx.doi.org/10.1128/mBio.01356-17,PMC5686532,29138299,CC BY,"Although viruses and viral capsids induce rapid immune responses, little is known about viral pathogen-associated molecular patterns (PAMPs) that are exhibited on their surface. Here, we demonstrate that the repeating protein subunit pattern common to most virus capsids is a molecular pattern that induces a Toll-like-receptor-2 (TLR2)-dependent antiviral immune response. This early antiviral immune response regulates the clearance of subsequent bacterial superinfections, which are a primary cause of morbidities associated with influenza virus infections. Utilizing this altered susceptibility to subsequent bacterial challenge as an outcome, we determined that multiple unrelated, empty, and replication-deficient capsids initiated early TLR2-dependent immune responses, similar to intact influenza virus or murine pneumovirus. These TLR2-mediated responses driven by the capsid were not dependent upon the capsid’s shape, size, origin, or amino acid sequence. However, they were dependent upon the multisubunit arrangement of the capsid proteins, because unlike intact capsids, individual capsid subunits did not enhance bacterial clearance. Further, we demonstrated that even a linear microfilament protein built from repeating protein subunits (F-actin), but not its monomer (G-actin), induced similar kinetics of subsequent bacterial clearance as did virus capsid. However, although capsids and F-actin induced similar bacterial clearance, in macrophages they required distinct TLR2 heterodimers for this response (TLR2/6 or TLR2/1, respectively) and different phagocyte populations were involved in the execution of these responses in vivo. Our results demonstrate that TLR2 responds to invading viral particles that are composed of repeating protein subunits, indicating that this common architecture of virus capsids is a previously unrecognized molecular pattern.",2017 Nov 14,"['Shepardson, Kelly M.', 'Schwarz, Benjamin', 'Larson, Kyle', 'Morton, Rachelle V.', 'Avera, John', 'McCoy, Kimberly', 'Caffrey, Alayna', 'Harmsen, Ann', 'Douglas, Trevor', 'Rynda-Apple, Agnieszka']",mBio,,,True
e44cf1ac39124d388901db43c0b4514577b08bc1,PMC,Induction of Antiviral Immune Response through Recognition of the Repeating Subunit Pattern of Viral Capsids Is Toll-Like Receptor 2 Dependent,http://dx.doi.org/10.1128/mBio.01356-17,PMC5686532,29138299,CC BY,"Although viruses and viral capsids induce rapid immune responses, little is known about viral pathogen-associated molecular patterns (PAMPs) that are exhibited on their surface. Here, we demonstrate that the repeating protein subunit pattern common to most virus capsids is a molecular pattern that induces a Toll-like-receptor-2 (TLR2)-dependent antiviral immune response. This early antiviral immune response regulates the clearance of subsequent bacterial superinfections, which are a primary cause of morbidities associated with influenza virus infections. Utilizing this altered susceptibility to subsequent bacterial challenge as an outcome, we determined that multiple unrelated, empty, and replication-deficient capsids initiated early TLR2-dependent immune responses, similar to intact influenza virus or murine pneumovirus. These TLR2-mediated responses driven by the capsid were not dependent upon the capsid’s shape, size, origin, or amino acid sequence. However, they were dependent upon the multisubunit arrangement of the capsid proteins, because unlike intact capsids, individual capsid subunits did not enhance bacterial clearance. Further, we demonstrated that even a linear microfilament protein built from repeating protein subunits (F-actin), but not its monomer (G-actin), induced similar kinetics of subsequent bacterial clearance as did virus capsid. However, although capsids and F-actin induced similar bacterial clearance, in macrophages they required distinct TLR2 heterodimers for this response (TLR2/6 or TLR2/1, respectively) and different phagocyte populations were involved in the execution of these responses in vivo. Our results demonstrate that TLR2 responds to invading viral particles that are composed of repeating protein subunits, indicating that this common architecture of virus capsids is a previously unrecognized molecular pattern.",2017 Nov 14,"['Shepardson, Kelly M.', 'Schwarz, Benjamin', 'Larson, Kyle', 'Morton, Rachelle V.', 'Avera, John', 'McCoy, Kimberly', 'Caffrey, Alayna', 'Harmsen, Ann', 'Douglas, Trevor', 'Rynda-Apple, Agnieszka']",mBio,,,False
d1ab379487b829f2a3d3f78f27a427f2dd87deda,PMC,"Porcine Hemagglutinating Encephalomyelitis Virus Enters Neuro-2a Cells via Clathrin-Mediated Endocytosis in a Rab5-, Cholesterol-, and pH-Dependent Manner",http://dx.doi.org/10.1128/JVI.01083-17,PMC5686734,28956766,CC BY,"Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurovirulent coronavirus that invades the central nervous system (CNS) in piglets. Although important progress has been made toward understanding the biology of PHEV, many aspects of its life cycle remain obscure. Here we dissected the molecular mechanism underlying cellular entry and intracellular trafficking of PHEV in mouse neuroblastoma (Neuro-2a) cells. We first performed a thin-section transmission electron microscopy (TEM) assay to characterize the kinetics of PHEV, and we found that viral entry and transfer occur via membranous coating-mediated endo- and exocytosis. To verify the roles of distinct endocytic pathways, systematic approaches were used, including pharmacological inhibition, RNA interference, confocal microscopy analysis, use of fluorescently labeled virus particles, and overexpression of a dominant negative (DN) mutant. Quantification of infected cells showed that PHEV enters cells by clathrin-mediated endocytosis (CME) and that low pH, dynamin, cholesterol, and Eps15 are indispensably involved in this process. Intriguingly, PHEV invasion leads to rapid actin rearrangement, suggesting that the intactness and dynamics of the actin cytoskeleton are positively correlated with viral endocytosis. We next investigated the trafficking of internalized PHEV and found that Rab5- and Rab7-dependent pathways are required for the initiation of a productive infection. Furthermore, a GTPase activation assay suggested that endogenous Rab5 is activated by PHEV and is crucial for viral progression. Our findings demonstrate that PHEV hijacks the CME and endosomal system of the host to enter and traffic within neural cells, providing new insights into PHEV pathogenesis and guidance for antiviral drug design. IMPORTANCE Porcine hemagglutinating encephalomyelitis virus (PHEV), a nonsegmented, positive-sense, single-stranded RNA coronavirus, invades the central nervous system (CNS) and causes neurological dysfunction. Neural cells are its targets for viral progression. However, the detailed mechanism underlying PHEV entry and trafficking remains unknown. PHEV is the etiological agent of porcine hemagglutinating encephalomyelitis, which is an acute and highly contagious disease that causes numerous deaths in suckling piglets and enormous economic losses in China. Understanding the viral entry pathway will not only advance our knowledge of PHEV infection and pathogenesis but also open new approaches to the development of novel therapeutic strategies. Therefore, we employed systematic approaches to dissect the internalization and intracellular trafficking mechanism of PHEV in Neuro-2a cells. This is the first report to describe the process of PHEV entry into nerve cells via clathrin-mediated endocytosis in a dynamin-, cholesterol-, and pH-dependent manner that requires Rab5 and Rab7.",2017 Nov 14,"['Li, Zi', 'Zhao, Kui', 'Lan, Yungang', 'Lv, Xiaoling', 'Hu, Shiyu', 'Guan, Jiyu', 'Lu, Huijun', 'Zhang, Jing', 'Shi, Junchao', 'Yang, Yawen', 'Song, Deguang', 'Gao, Feng', 'He, Wenqi']",J Virol,,,True
c865d4f4df0bee73efdd9413b23217e1b05b0f5e,PMC,Virus-triggered exacerbation in allergic asthmatic children: neutrophilic airway inflammation and alteration of virus sensors characterize a subgroup of patients,http://dx.doi.org/10.1186/s12931-017-0672-0,PMC5686805,29137638,CC BY,"BACKGROUND: Viruses are important triggers of asthma exacerbations. They are also detected outside of exacerbation. Alteration of anti-viral response in asthmatic patients has been shown although the mechanisms responsible for this defect remain unclear. The objective of this study was to compare in virus-infected and not-infected allergic asthmatic children, aged 6 to 16 years, admitted to hospital for a severe exacerbation, the innate immune response and especially the expression of pattern recognition receptor (PRR) and their function. METHODS: Virus identification was performed both during the exacerbation and at steady state (eight weeks later). Data assessed at both periods included clinical features, anti-viral response and inflammation (in sputum and plasma), and PRR expression/function in blood mononuclear cells. RESULTS: Viruses were identified in 46 out of 72 children (median age 8.9 years) during exacerbation, and among them, in 17 at steady state. IFN-β, IFN-γ and IL-29 levels in sputum and plasma were similar between infected and not infected patients at both times, as well as the expression of TLR3, RIG-I and MDA5 in blood monocytes and dendritic cells. Airway inflammation in infected patients was characterized by significantly higher IL-5 concentration and eosinophil count. Compared to patients only infected at exacerbation, the re-infected children significantly exhibited lower levels of IFN-γ in plasma and sputum at exacerbation associated with modifications in PRR expression and function in blood mononuclear cells. These re-infected patients also presented an airway neutrophilic inflammation at steady state. CONCLUSION: Our results reports in asthmatic children that impaired anti-viral response during virus-induced exacerbation is more pronounced in a subgroup of patients prone to re-infection by virus. This subgroup is characterized by altered PRR function and a different pattern of airway inflammation. TRIAL REGISTRATION: This multicenter prospective study was approved by the regional investigational review board (ref: 08/07). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-017-0672-0) contains supplementary material, which is available to authorized users.",2017 Nov 14,"['Deschildre, Antoine', 'Pichavant, Muriel', 'Engelmann, Ilka', 'Langlois, Carole', 'Drumez, Elodie', 'Pouessel, Guillaume', 'Boileau, Sophie', 'Romero-Cubero, David', 'Decleyre-Badiu, Irina', 'Dewilde, Anny', 'Hober, Didier', 'Néve, Véronique', 'Thumerelle, Caroline', 'Lejeune, Stéphanie', 'Mordacq, Clémence', 'Gosset, Philippe']",Respir Res,,,False
b36ea18c82602ddc5b1839cb5bce246c100d70a4,PMC,Virus-triggered exacerbation in allergic asthmatic children: neutrophilic airway inflammation and alteration of virus sensors characterize a subgroup of patients,http://dx.doi.org/10.1186/s12931-017-0672-0,PMC5686805,29137638,CC BY,"BACKGROUND: Viruses are important triggers of asthma exacerbations. They are also detected outside of exacerbation. Alteration of anti-viral response in asthmatic patients has been shown although the mechanisms responsible for this defect remain unclear. The objective of this study was to compare in virus-infected and not-infected allergic asthmatic children, aged 6 to 16 years, admitted to hospital for a severe exacerbation, the innate immune response and especially the expression of pattern recognition receptor (PRR) and their function. METHODS: Virus identification was performed both during the exacerbation and at steady state (eight weeks later). Data assessed at both periods included clinical features, anti-viral response and inflammation (in sputum and plasma), and PRR expression/function in blood mononuclear cells. RESULTS: Viruses were identified in 46 out of 72 children (median age 8.9 years) during exacerbation, and among them, in 17 at steady state. IFN-β, IFN-γ and IL-29 levels in sputum and plasma were similar between infected and not infected patients at both times, as well as the expression of TLR3, RIG-I and MDA5 in blood monocytes and dendritic cells. Airway inflammation in infected patients was characterized by significantly higher IL-5 concentration and eosinophil count. Compared to patients only infected at exacerbation, the re-infected children significantly exhibited lower levels of IFN-γ in plasma and sputum at exacerbation associated with modifications in PRR expression and function in blood mononuclear cells. These re-infected patients also presented an airway neutrophilic inflammation at steady state. CONCLUSION: Our results reports in asthmatic children that impaired anti-viral response during virus-induced exacerbation is more pronounced in a subgroup of patients prone to re-infection by virus. This subgroup is characterized by altered PRR function and a different pattern of airway inflammation. TRIAL REGISTRATION: This multicenter prospective study was approved by the regional investigational review board (ref: 08/07). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-017-0672-0) contains supplementary material, which is available to authorized users.",2017 Nov 14,"['Deschildre, Antoine', 'Pichavant, Muriel', 'Engelmann, Ilka', 'Langlois, Carole', 'Drumez, Elodie', 'Pouessel, Guillaume', 'Boileau, Sophie', 'Romero-Cubero, David', 'Decleyre-Badiu, Irina', 'Dewilde, Anny', 'Hober, Didier', 'Néve, Véronique', 'Thumerelle, Caroline', 'Lejeune, Stéphanie', 'Mordacq, Clémence', 'Gosset, Philippe']",Respir Res,,,False
691a90cab5096e5f0c1c28cc65c4890d1cbbfdfb,PMC,Virus-triggered exacerbation in allergic asthmatic children: neutrophilic airway inflammation and alteration of virus sensors characterize a subgroup of patients,http://dx.doi.org/10.1186/s12931-017-0672-0,PMC5686805,29137638,CC BY,"BACKGROUND: Viruses are important triggers of asthma exacerbations. They are also detected outside of exacerbation. Alteration of anti-viral response in asthmatic patients has been shown although the mechanisms responsible for this defect remain unclear. The objective of this study was to compare in virus-infected and not-infected allergic asthmatic children, aged 6 to 16 years, admitted to hospital for a severe exacerbation, the innate immune response and especially the expression of pattern recognition receptor (PRR) and their function. METHODS: Virus identification was performed both during the exacerbation and at steady state (eight weeks later). Data assessed at both periods included clinical features, anti-viral response and inflammation (in sputum and plasma), and PRR expression/function in blood mononuclear cells. RESULTS: Viruses were identified in 46 out of 72 children (median age 8.9 years) during exacerbation, and among them, in 17 at steady state. IFN-β, IFN-γ and IL-29 levels in sputum and plasma were similar between infected and not infected patients at both times, as well as the expression of TLR3, RIG-I and MDA5 in blood monocytes and dendritic cells. Airway inflammation in infected patients was characterized by significantly higher IL-5 concentration and eosinophil count. Compared to patients only infected at exacerbation, the re-infected children significantly exhibited lower levels of IFN-γ in plasma and sputum at exacerbation associated with modifications in PRR expression and function in blood mononuclear cells. These re-infected patients also presented an airway neutrophilic inflammation at steady state. CONCLUSION: Our results reports in asthmatic children that impaired anti-viral response during virus-induced exacerbation is more pronounced in a subgroup of patients prone to re-infection by virus. This subgroup is characterized by altered PRR function and a different pattern of airway inflammation. TRIAL REGISTRATION: This multicenter prospective study was approved by the regional investigational review board (ref: 08/07). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-017-0672-0) contains supplementary material, which is available to authorized users.",2017 Nov 14,"['Deschildre, Antoine', 'Pichavant, Muriel', 'Engelmann, Ilka', 'Langlois, Carole', 'Drumez, Elodie', 'Pouessel, Guillaume', 'Boileau, Sophie', 'Romero-Cubero, David', 'Decleyre-Badiu, Irina', 'Dewilde, Anny', 'Hober, Didier', 'Néve, Véronique', 'Thumerelle, Caroline', 'Lejeune, Stéphanie', 'Mordacq, Clémence', 'Gosset, Philippe']",Respir Res,,,False
39837437501e73db507e2d8dfe5a12bf5826fc31,PMC,Virus-triggered exacerbation in allergic asthmatic children: neutrophilic airway inflammation and alteration of virus sensors characterize a subgroup of patients,http://dx.doi.org/10.1186/s12931-017-0672-0,PMC5686805,29137638,CC BY,"BACKGROUND: Viruses are important triggers of asthma exacerbations. They are also detected outside of exacerbation. Alteration of anti-viral response in asthmatic patients has been shown although the mechanisms responsible for this defect remain unclear. The objective of this study was to compare in virus-infected and not-infected allergic asthmatic children, aged 6 to 16 years, admitted to hospital for a severe exacerbation, the innate immune response and especially the expression of pattern recognition receptor (PRR) and their function. METHODS: Virus identification was performed both during the exacerbation and at steady state (eight weeks later). Data assessed at both periods included clinical features, anti-viral response and inflammation (in sputum and plasma), and PRR expression/function in blood mononuclear cells. RESULTS: Viruses were identified in 46 out of 72 children (median age 8.9 years) during exacerbation, and among them, in 17 at steady state. IFN-β, IFN-γ and IL-29 levels in sputum and plasma were similar between infected and not infected patients at both times, as well as the expression of TLR3, RIG-I and MDA5 in blood monocytes and dendritic cells. Airway inflammation in infected patients was characterized by significantly higher IL-5 concentration and eosinophil count. Compared to patients only infected at exacerbation, the re-infected children significantly exhibited lower levels of IFN-γ in plasma and sputum at exacerbation associated with modifications in PRR expression and function in blood mononuclear cells. These re-infected patients also presented an airway neutrophilic inflammation at steady state. CONCLUSION: Our results reports in asthmatic children that impaired anti-viral response during virus-induced exacerbation is more pronounced in a subgroup of patients prone to re-infection by virus. This subgroup is characterized by altered PRR function and a different pattern of airway inflammation. TRIAL REGISTRATION: This multicenter prospective study was approved by the regional investigational review board (ref: 08/07). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-017-0672-0) contains supplementary material, which is available to authorized users.",2017 Nov 14,"['Deschildre, Antoine', 'Pichavant, Muriel', 'Engelmann, Ilka', 'Langlois, Carole', 'Drumez, Elodie', 'Pouessel, Guillaume', 'Boileau, Sophie', 'Romero-Cubero, David', 'Decleyre-Badiu, Irina', 'Dewilde, Anny', 'Hober, Didier', 'Néve, Véronique', 'Thumerelle, Caroline', 'Lejeune, Stéphanie', 'Mordacq, Clémence', 'Gosset, Philippe']",Respir Res,,,False
23341a63974ab27c419473611fd28250356df91f,PMC,Virus-triggered exacerbation in allergic asthmatic children: neutrophilic airway inflammation and alteration of virus sensors characterize a subgroup of patients,http://dx.doi.org/10.1186/s12931-017-0672-0,PMC5686805,29137638,CC BY,"BACKGROUND: Viruses are important triggers of asthma exacerbations. They are also detected outside of exacerbation. Alteration of anti-viral response in asthmatic patients has been shown although the mechanisms responsible for this defect remain unclear. The objective of this study was to compare in virus-infected and not-infected allergic asthmatic children, aged 6 to 16 years, admitted to hospital for a severe exacerbation, the innate immune response and especially the expression of pattern recognition receptor (PRR) and their function. METHODS: Virus identification was performed both during the exacerbation and at steady state (eight weeks later). Data assessed at both periods included clinical features, anti-viral response and inflammation (in sputum and plasma), and PRR expression/function in blood mononuclear cells. RESULTS: Viruses were identified in 46 out of 72 children (median age 8.9 years) during exacerbation, and among them, in 17 at steady state. IFN-β, IFN-γ and IL-29 levels in sputum and plasma were similar between infected and not infected patients at both times, as well as the expression of TLR3, RIG-I and MDA5 in blood monocytes and dendritic cells. Airway inflammation in infected patients was characterized by significantly higher IL-5 concentration and eosinophil count. Compared to patients only infected at exacerbation, the re-infected children significantly exhibited lower levels of IFN-γ in plasma and sputum at exacerbation associated with modifications in PRR expression and function in blood mononuclear cells. These re-infected patients also presented an airway neutrophilic inflammation at steady state. CONCLUSION: Our results reports in asthmatic children that impaired anti-viral response during virus-induced exacerbation is more pronounced in a subgroup of patients prone to re-infection by virus. This subgroup is characterized by altered PRR function and a different pattern of airway inflammation. TRIAL REGISTRATION: This multicenter prospective study was approved by the regional investigational review board (ref: 08/07). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-017-0672-0) contains supplementary material, which is available to authorized users.",2017 Nov 14,"['Deschildre, Antoine', 'Pichavant, Muriel', 'Engelmann, Ilka', 'Langlois, Carole', 'Drumez, Elodie', 'Pouessel, Guillaume', 'Boileau, Sophie', 'Romero-Cubero, David', 'Decleyre-Badiu, Irina', 'Dewilde, Anny', 'Hober, Didier', 'Néve, Véronique', 'Thumerelle, Caroline', 'Lejeune, Stéphanie', 'Mordacq, Clémence', 'Gosset, Philippe']",Respir Res,,,False
ea663ab1d3a4b40c13029f5e0f5dfe1c21a23720,PMC,Virus-triggered exacerbation in allergic asthmatic children: neutrophilic airway inflammation and alteration of virus sensors characterize a subgroup of patients,http://dx.doi.org/10.1186/s12931-017-0672-0,PMC5686805,29137638,CC BY,"BACKGROUND: Viruses are important triggers of asthma exacerbations. They are also detected outside of exacerbation. Alteration of anti-viral response in asthmatic patients has been shown although the mechanisms responsible for this defect remain unclear. The objective of this study was to compare in virus-infected and not-infected allergic asthmatic children, aged 6 to 16 years, admitted to hospital for a severe exacerbation, the innate immune response and especially the expression of pattern recognition receptor (PRR) and their function. METHODS: Virus identification was performed both during the exacerbation and at steady state (eight weeks later). Data assessed at both periods included clinical features, anti-viral response and inflammation (in sputum and plasma), and PRR expression/function in blood mononuclear cells. RESULTS: Viruses were identified in 46 out of 72 children (median age 8.9 years) during exacerbation, and among them, in 17 at steady state. IFN-β, IFN-γ and IL-29 levels in sputum and plasma were similar between infected and not infected patients at both times, as well as the expression of TLR3, RIG-I and MDA5 in blood monocytes and dendritic cells. Airway inflammation in infected patients was characterized by significantly higher IL-5 concentration and eosinophil count. Compared to patients only infected at exacerbation, the re-infected children significantly exhibited lower levels of IFN-γ in plasma and sputum at exacerbation associated with modifications in PRR expression and function in blood mononuclear cells. These re-infected patients also presented an airway neutrophilic inflammation at steady state. CONCLUSION: Our results reports in asthmatic children that impaired anti-viral response during virus-induced exacerbation is more pronounced in a subgroup of patients prone to re-infection by virus. This subgroup is characterized by altered PRR function and a different pattern of airway inflammation. TRIAL REGISTRATION: This multicenter prospective study was approved by the regional investigational review board (ref: 08/07). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-017-0672-0) contains supplementary material, which is available to authorized users.",2017 Nov 14,"['Deschildre, Antoine', 'Pichavant, Muriel', 'Engelmann, Ilka', 'Langlois, Carole', 'Drumez, Elodie', 'Pouessel, Guillaume', 'Boileau, Sophie', 'Romero-Cubero, David', 'Decleyre-Badiu, Irina', 'Dewilde, Anny', 'Hober, Didier', 'Néve, Véronique', 'Thumerelle, Caroline', 'Lejeune, Stéphanie', 'Mordacq, Clémence', 'Gosset, Philippe']",Respir Res,,,False
67a6df71488c27e33103ba6928ea2b1170c0fc52,PMC,Virus-triggered exacerbation in allergic asthmatic children: neutrophilic airway inflammation and alteration of virus sensors characterize a subgroup of patients,http://dx.doi.org/10.1186/s12931-017-0672-0,PMC5686805,29137638,CC BY,"BACKGROUND: Viruses are important triggers of asthma exacerbations. They are also detected outside of exacerbation. Alteration of anti-viral response in asthmatic patients has been shown although the mechanisms responsible for this defect remain unclear. The objective of this study was to compare in virus-infected and not-infected allergic asthmatic children, aged 6 to 16 years, admitted to hospital for a severe exacerbation, the innate immune response and especially the expression of pattern recognition receptor (PRR) and their function. METHODS: Virus identification was performed both during the exacerbation and at steady state (eight weeks later). Data assessed at both periods included clinical features, anti-viral response and inflammation (in sputum and plasma), and PRR expression/function in blood mononuclear cells. RESULTS: Viruses were identified in 46 out of 72 children (median age 8.9 years) during exacerbation, and among them, in 17 at steady state. IFN-β, IFN-γ and IL-29 levels in sputum and plasma were similar between infected and not infected patients at both times, as well as the expression of TLR3, RIG-I and MDA5 in blood monocytes and dendritic cells. Airway inflammation in infected patients was characterized by significantly higher IL-5 concentration and eosinophil count. Compared to patients only infected at exacerbation, the re-infected children significantly exhibited lower levels of IFN-γ in plasma and sputum at exacerbation associated with modifications in PRR expression and function in blood mononuclear cells. These re-infected patients also presented an airway neutrophilic inflammation at steady state. CONCLUSION: Our results reports in asthmatic children that impaired anti-viral response during virus-induced exacerbation is more pronounced in a subgroup of patients prone to re-infection by virus. This subgroup is characterized by altered PRR function and a different pattern of airway inflammation. TRIAL REGISTRATION: This multicenter prospective study was approved by the regional investigational review board (ref: 08/07). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-017-0672-0) contains supplementary material, which is available to authorized users.",2017 Nov 14,"['Deschildre, Antoine', 'Pichavant, Muriel', 'Engelmann, Ilka', 'Langlois, Carole', 'Drumez, Elodie', 'Pouessel, Guillaume', 'Boileau, Sophie', 'Romero-Cubero, David', 'Decleyre-Badiu, Irina', 'Dewilde, Anny', 'Hober, Didier', 'Néve, Véronique', 'Thumerelle, Caroline', 'Lejeune, Stéphanie', 'Mordacq, Clémence', 'Gosset, Philippe']",Respir Res,,,False
5bc8dd515058e0fe94c6fc4a2c3cb85572030fec,PMC,Virus-triggered exacerbation in allergic asthmatic children: neutrophilic airway inflammation and alteration of virus sensors characterize a subgroup of patients,http://dx.doi.org/10.1186/s12931-017-0672-0,PMC5686805,29137638,CC BY,"BACKGROUND: Viruses are important triggers of asthma exacerbations. They are also detected outside of exacerbation. Alteration of anti-viral response in asthmatic patients has been shown although the mechanisms responsible for this defect remain unclear. The objective of this study was to compare in virus-infected and not-infected allergic asthmatic children, aged 6 to 16 years, admitted to hospital for a severe exacerbation, the innate immune response and especially the expression of pattern recognition receptor (PRR) and their function. METHODS: Virus identification was performed both during the exacerbation and at steady state (eight weeks later). Data assessed at both periods included clinical features, anti-viral response and inflammation (in sputum and plasma), and PRR expression/function in blood mononuclear cells. RESULTS: Viruses were identified in 46 out of 72 children (median age 8.9 years) during exacerbation, and among them, in 17 at steady state. IFN-β, IFN-γ and IL-29 levels in sputum and plasma were similar between infected and not infected patients at both times, as well as the expression of TLR3, RIG-I and MDA5 in blood monocytes and dendritic cells. Airway inflammation in infected patients was characterized by significantly higher IL-5 concentration and eosinophil count. Compared to patients only infected at exacerbation, the re-infected children significantly exhibited lower levels of IFN-γ in plasma and sputum at exacerbation associated with modifications in PRR expression and function in blood mononuclear cells. These re-infected patients also presented an airway neutrophilic inflammation at steady state. CONCLUSION: Our results reports in asthmatic children that impaired anti-viral response during virus-induced exacerbation is more pronounced in a subgroup of patients prone to re-infection by virus. This subgroup is characterized by altered PRR function and a different pattern of airway inflammation. TRIAL REGISTRATION: This multicenter prospective study was approved by the regional investigational review board (ref: 08/07). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-017-0672-0) contains supplementary material, which is available to authorized users.",2017 Nov 14,"['Deschildre, Antoine', 'Pichavant, Muriel', 'Engelmann, Ilka', 'Langlois, Carole', 'Drumez, Elodie', 'Pouessel, Guillaume', 'Boileau, Sophie', 'Romero-Cubero, David', 'Decleyre-Badiu, Irina', 'Dewilde, Anny', 'Hober, Didier', 'Néve, Véronique', 'Thumerelle, Caroline', 'Lejeune, Stéphanie', 'Mordacq, Clémence', 'Gosset, Philippe']",Respir Res,,,True
28a98145eda693bae14b52abfc3d37ced6c5fd90,PMC,Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis,http://dx.doi.org/10.1128/mSphere.00346-17,PMC5687918,29152578,CC BY,"Coronaviruses (CoVs) encode a mixture of highly conserved and novel genes, as well as genetic elements necessary for infection and pathogenesis, raising the possibility of common targets for attenuation and therapeutic design. In this study, we focused on highly conserved nonstructural protein 16 (NSP16), a viral 2′O-methyltransferase (2′O-MTase) that encodes critical functions in immune modulation and infection. Using reverse genetics, we disrupted a key motif in the conserved KDKE motif of Middle East respiratory syndrome CoV (MERS-CoV) NSP16 (D130A) and evaluated the effect on viral infection and pathogenesis. While the absence of 2′O-MTase activity had only a marginal impact on propagation and replication in Vero cells, dNSP16 mutant MERS-CoV demonstrated significant attenuation relative to the control both in primary human airway cell cultures and in vivo. Further examination indicated that dNSP16 mutant MERS-CoV had a type I interferon (IFN)-based attenuation and was partially restored in the absence of molecules of IFN-induced proteins with tetratricopeptide repeats. Importantly, the robust attenuation permitted the use of dNSP16 mutant MERS-CoV as a live attenuated vaccine platform protecting from a challenge with a mouse-adapted MERS-CoV strain. These studies demonstrate the importance of the conserved 2′O-MTase activity for CoV pathogenesis and highlight NSP16 as a conserved universal target for rapid live attenuated vaccine design in an expanding CoV outbreak setting. IMPORTANCE Coronavirus (CoV) emergence in both humans and livestock represents a significant threat to global public health, as evidenced by the sudden emergence of severe acute respiratory syndrome CoV (SARS-CoV), MERS-CoV, porcine epidemic diarrhea virus, and swine delta CoV in the 21st century. These studies describe an approach that effectively targets the highly conserved 2′O-MTase activity of CoVs for attenuation. With clear understanding of the IFN/IFIT (IFN-induced proteins with tetratricopeptide repeats)-based mechanism, NSP16 mutants provide a suitable target for a live attenuated vaccine platform, as well as therapeutic development for both current and future emergent CoV strains. Importantly, other approaches targeting other conserved pan-CoV functions have not yet proven effective against MERS-CoV, illustrating the broad applicability of targeting viral 2′O-MTase function across CoVs.",2017 Nov 15,"['Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Mitchell, Hugh D.', 'Dinnon, Kenneth H.', 'Leist, Sarah R.', 'Yount, Boyd L.', 'Graham, Rachel L.', 'McAnarney, Eileen T.', 'Stratton, Kelly G.', 'Cockrell, Adam S.', 'Debbink, Kari', 'Sims, Amy C.', 'Waters, Katrina M.', 'Baric, Ralph S.']",mSphere,,,True
2079a44557da9aa2ce74d6af8ac0e8a344c1ad8d,PMC,What Synthesis Methodology Should I Use? A Review and Analysis of Approaches to Research Synthesis,http://dx.doi.org/10.3934/publichealth.2016.1.172,PMC5690272,29546155,CC BY,"BACKGROUND: When we began this process, we were doctoral students and a faculty member in a research methods course. As students, we were facing a review of the literature for our dissertations. We encountered several different ways of conducting a review but were unable to locate any resources that synthesized all of the various synthesis methodologies. Our purpose is to present a comprehensive overview and assessment of the main approaches to research synthesis. We use ‘research synthesis’ as a broad overarching term to describe various approaches to combining, integrating, and synthesizing research findings. METHODS: We conducted an integrative review of the literature to explore the historical, contextual, and evolving nature of research synthesis. We searched five databases, reviewed websites of key organizations, hand-searched several journals, and examined relevant texts from the reference lists of the documents we had already obtained. RESULTS: We identified four broad categories of research synthesis methodology including conventional, quantitative, qualitative, and emerging syntheses. Each of the broad categories was compared to the others on the following: key characteristics, purpose, method, product, context, underlying assumptions, unit of analysis, strengths and limitations, and when to use each approach. CONCLUSIONS: The current state of research synthesis reflects significant advancements in emerging synthesis studies that integrate diverse data types and sources. New approaches to research synthesis provide a much broader range of review alternatives available to health and social science students and researchers.",2016 Mar 30,"['Schick-Makaroff, Kara', 'MacDonald, Marjorie', 'Plummer, Marilyn', 'Burgess, Judy', 'Neander, Wendy']",AIMS Public Health,,,True
1291b42497aeef11d21f1fcf33ee7e910a3396dd,PMC,Public Health Emergency of International Concern (PHEIC) has Declared Twice in 2014; Polio and Ebola at the Top,http://dx.doi.org/10.3934/publichealth.2015.2.218,PMC5690278,29546106,CC BY,"BACKGROUND: The current Ebola outbreak in West Africa and the large scale wild Polio virus outbreak in several countries are the top most issues among international public health and scientific communities' debates and concerns. These two outbreaks were judged to be declared as Public Health Emergency of International Concern (PHEIC) during 2014. This is the first time ever to have such circumstance of two PHEICs at the same time. DISCUSSION: PHEIC, which has to be declared by WHO Director General after a recommendation of IHR Emergency Committee; is observed to start in countries with fragile health system and conflict areas. Then it rapidly spread to threaten the global public health. The year 2014 has uniquely witnessed declaration of two events as PHEIC according to IHR (2005); Polio and Ebola Virus Disease (EVD). Both outbreaks are caused by viruses such as H1N1 which was previously declared as PHEIC in 2009. SUMMARY: Public Health Emergencies of International Concern in 2014 occurred in countries with weak health systems and conflicts and threatening the whole globe. International collaborative work is required to contain the event and to mobilize resources/capacities between countries. Moreover, public health surveillance systems as core capacity for IHR (2005) should be strengthened in all countries with focus on those with limited capacity and ongoing conflicts. The ultimate aim is timely detection of potential PHEIC events in the future along with early preparedness and response plans.",2015 Jun 5,"['Soghaier, Mohammed A.', 'Saeed, Khwaja M.I.', 'Zaman, Khushhal K.']",AIMS Public Health,,,True
848c234214cbc5eeb1d64a043ff097e32e8ebff0,PMC,"Suppression and resolution of autoimmune arthritis by rhesus θ-defensin-1, an immunomodulatory macrocyclic peptide",http://dx.doi.org/10.1371/journal.pone.0187868,PMC5690597,29145473,CC BY,"θ-defensins constitute a family of macrocyclic peptides expressed exclusively in Old World monkeys. The peptides are pleiotropic effectors of innate immunity, possessing broad spectrum antimicrobial activities and immunoregulatory properties. Here we report that rhesus θ-defensin 1 (RTD-1) is highly effective in arresting and reversing joint disease in a rodent model of rheumatoid arthritis (RA). Parenteral RTD-1 treatment of DA/OlaHsd rats with established pristane-induced arthritis (PIA) rapidly suppressed joint disease progression, restored limb mobility, and preserved normal joint architecture. RTD-1 significantly reduced joint IL-1β levels compared with controls. RTD-1 dose-dependently inhibited fibroblast-like synoviocyte (FLS) invasiveness and FLS IL-6 production. Consistent with the inhibition of FLS invasiveness, RTD-1 was a potent inhibitor of arthritogenic proteases including ADAMs 17 and 10 which activate TNFα, and inhibited matrix metalloproteases, and cathepsin K. RTD-1 was non-toxic, non-immunogenic, and effective when administered as infrequently as once every five days. Thus θ-defensins, which are absent in humans, have potential as retroevolutionary biologics for the treatment of RA.",2017 Nov 16,"['Schaal, Justin B.', 'Tran, Dat Q.', 'Subramanian, Akshay', 'Patel, Reshma', 'Laragione, Teresina', 'Roberts, Kevin D.', 'Trinh, Katie', 'Tongaonkar, Prasad', 'Tran, Patti A.', 'Minond, Dmitriy', 'Fields, Gregg B.', 'Beringer, Paul', 'Ouellette, André J.', 'Gulko, Percio S.', 'Selsted, Michael E.']",PLoS One,,,True
bf8f5eb3d2fcf7df49dbd5b38a1db29c8b60dbd5,PMC,"Suppression and resolution of autoimmune arthritis by rhesus θ-defensin-1, an immunomodulatory macrocyclic peptide",http://dx.doi.org/10.1371/journal.pone.0187868,PMC5690597,29145473,CC BY,"θ-defensins constitute a family of macrocyclic peptides expressed exclusively in Old World monkeys. The peptides are pleiotropic effectors of innate immunity, possessing broad spectrum antimicrobial activities and immunoregulatory properties. Here we report that rhesus θ-defensin 1 (RTD-1) is highly effective in arresting and reversing joint disease in a rodent model of rheumatoid arthritis (RA). Parenteral RTD-1 treatment of DA/OlaHsd rats with established pristane-induced arthritis (PIA) rapidly suppressed joint disease progression, restored limb mobility, and preserved normal joint architecture. RTD-1 significantly reduced joint IL-1β levels compared with controls. RTD-1 dose-dependently inhibited fibroblast-like synoviocyte (FLS) invasiveness and FLS IL-6 production. Consistent with the inhibition of FLS invasiveness, RTD-1 was a potent inhibitor of arthritogenic proteases including ADAMs 17 and 10 which activate TNFα, and inhibited matrix metalloproteases, and cathepsin K. RTD-1 was non-toxic, non-immunogenic, and effective when administered as infrequently as once every five days. Thus θ-defensins, which are absent in humans, have potential as retroevolutionary biologics for the treatment of RA.",2017 Nov 16,"['Schaal, Justin B.', 'Tran, Dat Q.', 'Subramanian, Akshay', 'Patel, Reshma', 'Laragione, Teresina', 'Roberts, Kevin D.', 'Trinh, Katie', 'Tongaonkar, Prasad', 'Tran, Patti A.', 'Minond, Dmitriy', 'Fields, Gregg B.', 'Beringer, Paul', 'Ouellette, André J.', 'Gulko, Percio S.', 'Selsted, Michael E.']",PLoS One,,,False
c1a54ec890c135c78fb0c2b0b9c1b96ac2b945eb,PMC,Oncolytic Reovirus Infection Is Facilitated by the Autophagic Machinery,http://dx.doi.org/10.3390/v9100266,PMC5691618,28934149,CC BY,"Mammalian reovirus is a double-stranded RNA virus that selectively infects and lyses transformed cells, making it an attractive oncolytic agent. Despite clinical evidence for anti-tumor activity, its efficacy as a stand-alone therapy remains to be improved. The success of future trials can be greatly influenced by the identification and the regulation of the cellular pathways that are important for reovirus replication and oncolysis. Here, we demonstrate that reovirus induces autophagy in several cell lines, evident from the formation of Atg5-Atg12 complexes, microtubule-associated protein 1 light chain 3 (LC3) lipidation, p62 degradation, the appearance of acidic vesicular organelles, and LC3 puncta. Furthermore, in electron microscopic images of reovirus-infected cells, autophagosomes were observed without evident association with viral factories. Using UV-inactivated reovirus, we demonstrate that a productive reovirus infection facilitates the induction of autophagy. Importantly, knock-out cell lines for specific autophagy-related genes revealed that the expression of Atg3 and Atg5 but not Atg13 facilitates reovirus replication. These findings highlight a central and Atg13-independent role for the autophagy machinery in facilitating reovirus infection and contribute to a better understanding of reovirus-host interactions.",2017 Sep 21,"['Kemp, Vera', 'Dautzenberg, Iris J. C.', 'Limpens, Ronald W.', 'van den Wollenberg, Diana J. M.', 'Hoeben, Rob C.']",Viruses,,,True
13d39b597ef6853185ff1e43a4420984a8c6416e,PMC,Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins,http://dx.doi.org/10.3390/v9100271,PMC5691623,28946654,CC BY,"Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.",2017 Sep 25,"['Bulanova, Daria', 'Ianevski, Aleksandr', 'Bugai, Andrii', 'Akimov, Yevhen', 'Kuivanen, Suvi', 'Paavilainen, Henrik', 'Kakkola, Laura', 'Nandania, Jatin', 'Turunen, Laura', 'Ohman, Tiina', 'Ala-Hongisto, Hanna', 'Pesonen, Hanna M.', 'Kuisma, Marika S.', 'Honkimaa, Anni', 'Walton, Emma L.', 'Oksenych, Valentyn', 'Lorey, Martina B.', 'Guschin, Dmitry', 'Shim, Jungmin', 'Kim, Jinhee', 'Than, Thoa T.', 'Chang, So Young', 'Hukkanen, Veijo', 'Kulesskiy, Evgeny', 'Marjomaki, Varpu S.', 'Julkunen, Ilkka', 'Nyman, Tuula A.', 'Matikainen, Sampsa', 'Saarela, Jani S.', 'Sane, Famara', 'Hober, Didier', 'Gabriel, Gülsah', 'De Brabander, Jef K.', 'Martikainen, Miika', 'Windisch, Marc P.', 'Min, Ji-Young', 'Bruzzone, Roberto', 'Aittokallio, Tero', 'Vähä-Koskela, Markus', 'Vapalahti, Olli', 'Pulk, Arto', 'Velagapudi, Vidya', 'Kainov, Denis E.']",Viruses,,,True
27053e838296b253c42a6b343940a6aec83a7ebb,PMC,Immunogenicity of eGFP-Marked Recombinant Lactobacillus casei against Transmissible Gastroenteritis Virus and Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.3390/v9100274,PMC5691626,28946696,CC BY,"Porcine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV) are the causative agents of highly fatal acute diarrhea in pigs, resulting in enormous losses in the pig industry worldwide. To develop an effective bivalent oral vaccine against TGEV and PEDV infection, the D antigenic site of the TGEV spike (S) protein and the major antigen site (core neutralizing epitope—COE) of the PEDV S protein were used as immunogens, and the enhanced green fluorescent protein (eGFP) gene was used as a reporter to construct genetically engineered Lactobacillus casei rLpPG(F)-T7g10-eGFP-6D-COE. The expression of proteins of interest by the recombinant L. casei was confirmed by confocal laser scanning microscopy and a Western blot assay, and the immunogenicity of rLpPG(F)-T7g10-eGFP-6D-COE in orally immunized mice was evaluated. The results showed that levels of anti-PEDV and anti-TGEV serum immunoglobulin G (IgG) and mucosal secreted immunoglobulin A (sIgA) antibodies obtained from the mice immunized with rLpPG(F)-T7g10-eGFP-6D-COE, as well as the proliferation levels of lymphocytes, were significantly higher than those in mice orally administered phosphate-buffered saline (PBS) or rLpPG-T7g10. Moreover, the serum IgG antibodies showed neutralizing effects against PEDV and TGEV. Our data suggest that the antibiotic resistance-free genetically engineered L. casei bivalent oral vaccine provides a safe and promising strategy for vaccine development against PEDV and TGEV.",2017 Sep 25,"['Yu, Meiling', 'Wang, Li', 'Ma, Sunting', 'Wang, Xiaona', 'Wang, Yusai', 'Xiao, Ya', 'Jiang, Yanping', 'Qiao, Xinyuan', 'Tang, Lijie', 'Xu, Yigang', 'Li, Yijing']",Viruses,,,True
63b21e59e43206a09eaa36fdc5233f22af7515e3,PMC,Telomere Dynamics in Immune Senescence and Exhaustion Triggered by Chronic Viral Infection,http://dx.doi.org/10.3390/v9100289,PMC5691640,28981470,CC BY,"The progressive loss of immunological memory during aging correlates with a reduced proliferative capacity and shortened telomeres of T cells. Growing evidence suggests that this phenotype is recapitulated during chronic viral infection. The antigenic volume imposed by persistent and latent viruses exposes the immune system to unique challenges that lead to host T-cell exhaustion, characterized by impaired T-cell functions. These dysfunctional memory T cells lack telomerase, the protein capable of extending and stabilizing chromosome ends, imposing constraints on telomere dynamics. A deleterious consequence of this excessive telomere shortening is the premature induction of replicative senescence of viral-specific CD8+ memory T cells. While senescent cells are unable to expand, they can survive for extended periods of time and are more resistant to apoptotic signals. This review takes a closer look at T-cell exhaustion in chronic viruses known to cause human disease: Epstein–Barr virus (EBV), Hepatitis B/C/D virus (HBV/HCV/HDV), human herpesvirus 8 (HHV-8), human immunodeficiency virus (HIV), human T-cell leukemia virus type I (HTLV-I), human papillomavirus (HPV), herpes simplex virus-1/2 (HSV-1/2), and Varicella–Zoster virus (VZV). Current literature linking T-cell exhaustion with critical telomere lengths and immune senescence are discussed. The concept that enduring antigen stimulation leads to T-cell exhaustion that favors telomere attrition and a cell fate marked by enhanced T-cell senescence appears to be a common endpoint to chronic viral infections.",2017 Oct 5,"['Bellon, Marcia', 'Nicot, Christophe']",Viruses,,,True
792fa8ba0747cfa42ffa4247f036bc214e944185,PMC,Polyprotein Processing as a Determinant for In Vitro Activity of Semliki Forest Virus Replicase,http://dx.doi.org/10.3390/v9100292,PMC5691643,28991178,CC BY,"Semliki Forest virus (SFV) is an arthropod-borne alphavirus that induces membrane invaginations (spherules) in host cells. These harbor the viral replication complexes (RC) that synthesize viral RNA. Alphaviruses have four replicase or nonstructural proteins (nsPs), nsP1–4, expressed as polyprotein P1234. An early RC, which synthesizes minus-strand RNA, is formed by the polyprotein P123 and the polymerase nsP4. Further proteolytic cleavage results in a late RC consisting of nsP1–4 and synthesizing plus strands. Here, we show that only the late RCs are highly active in RNA synthesis in vitro. Furthermore, we demonstrate that active RCs can be isolated from both virus-infected cells and cells transfected with the wild-type replicase in combination with a plasmid expressing a template RNA. When an uncleavable polyprotein P123 and polymerase nsP4 were expressed together with a template, high levels of minus-strand RNA were produced in cells, but RCs isolated from these cells were hardly active in vitro. Furthermore, we observed that the uncleavable polyprotein P123 and polymerase nsP4, which have previously been shown to form spherules even in the absence of the template, did not replicate an exogenous template. Consequently, we hypothesize that the replicase proteins were sequestered in spherules and were no longer able to recruit a template.",2017 Oct 7,"['Pietilä, Maija K.', 'Albulescu, Irina C.', 'van Hemert, Martijn J.', 'Ahola, Tero']",Viruses,,,True
bbffb6a287ece187b7ad9ceb9f703854b0ea8e1d,PMC,The Battle of RNA Synthesis: Virus versus Host,http://dx.doi.org/10.3390/v9100309,PMC5691660,29065472,CC BY,"Transcription control is the foundation of gene regulation. Whereas a cell is fully equipped for this task, viruses often depend on the host to supply tools for their transcription program. Over the course of evolution and adaptation, viruses have found diverse ways to optimally exploit cellular host processes such as transcription to their own benefit. Just as cells are increasingly understood to employ nascent RNAs in transcription regulation, recent discoveries are revealing how viruses use nascent RNAs to benefit their own gene expression. In this review, we first outline the two different transcription programs used by viruses, i.e., transcription (DNA-dependent) and RNA-dependent RNA synthesis. Subsequently, we use the distinct stages (initiation, elongation, termination) to describe the latest insights into nascent RNA-mediated regulation in the context of each relevant stage.",2017 Oct 21,"['Harwig, Alex', 'Landick, Robert', 'Berkhout, Ben']",Viruses,,,True
51f9ab9c7010dae7a662a33f0fd32e91a2001523,PMC,Longitudinal survey of two serotine bat (Eptesicus serotinus) maternity colonies exposed to EBLV-1 (European Bat Lyssavirus type 1): Assessment of survival and serological status variations using capture-recapture models,http://dx.doi.org/10.1371/journal.pntd.0006048,PMC5693283,29149215,CC BY,"This study describes two longitudinal serological surveys of European Bat Lyssavirus type 1 (EBLV-1) antibodies in serotine bat (Eptesicus serotinus) maternity colonies located in the North-East of France. This species is currently considered as the main EBLV-1 reservoir. Multievent capture-recapture models were used to determine the factors influencing bat rabies transmission as this method accounts for imperfect detection and uncertainty in disease states. Considering the period of study, analyses revealed that survival and recapture probabilities were not affected by the serological status of individuals, confirming the capacity of bats to be exposed to lyssaviruses without dying. Five bats have been found with EBLV-1 RNA in the saliva at the start of the study, suggesting they were caught during virus excretion period. Among these bats, one was interestingly recaptured one year later and harbored a seropositive status. Along the survey, some others bats have been observed to both seroconvert (i.e. move from a negative to a positive serological status) and serorevert (i.e. move from a positive to a negative serological status). Peak of seroprevalence reached 34% and 70% in site A and B respectively. On one of the 2 sites, global decrease of seroprevalence was observed all along the study period nuanced by oscillation intervals of approximately 2–3 years supporting the oscillation infection dynamics hypothesized during a previous EBLV-1 study in a Myotis myotis colony. Seroprevalence were affected by significantly higher seroprevalence in summer than in spring. The maximum time observed between successive positive serological statuses of a bat demonstrated the potential persistence of neutralizing antibodies for at least 4 years. At last, EBLV-1 serological status transitions have been shown driven by age category with higher seroreversion frequencies in adults than in juvenile. Juveniles and female adults seemed indeed acting as distinct drivers of the rabies virus dynamics, hypothesis have been addressed but their exact role in the EBLV-1 transmission still need to be specified.",2017 Nov 17,"['Robardet, Emmanuelle', 'Borel, Christophe', 'Moinet, Marie', 'Jouan, Dorothée', 'Wasniewski, Marine', 'Barrat, Jacques', 'Boué, Franck', 'Montchâtre-Leroy, Elodie', 'Servat, Alexandre', 'Gimenez, Olivier', 'Cliquet, Florence', 'Picard-Meyer, Evelyne']",PLoS Negl Trop Dis,,,True
7ca1fae02f72d4e0687ac4584d96d7d4bc98b34c,PMC,"The introduction of dengue follows transportation infrastructure changes in the state of Acre, Brazil: A network-based analysis",http://dx.doi.org/10.1371/journal.pntd.0006070,PMC5693297,29149175,CC BY,"Human mobility, presence and passive transportation of Aedes aegypti mosquito, and environmental characteristics are a group of factors which contribute to the success of dengue spread and establishment. To understand this process, we assess data from dengue national and municipal basins regarding population and demographics, transportation network, human mobility, and Ae. aegypti monitoring for the Brazilian state of Acre since the first recorded dengue case in the year 2000 to the year 2015. During this period, several changes in Acre’s transport infrastructure and urbanization have been started. To reconstruct the process of dengue introduction in Acre, we propose an analytic framework based on concepts used in malaria literature, namely vulnerability and receptivity, to inform risk assessments in dengue-free regions as well as network theory concepts for disease invasion and propagation. We calculate the probability of dengue importation to Acre from other Brazilian states, the evolution of dengue spread between Acrean municipalities and dengue establishment in the state. Our findings suggest that the landscape changes associated with human mobility have created favorable conditions for the establishment of dengue virus transmission in Acre. The revitalization of its major roads, as well as the increased accessibility by air to and within the state, have increased dengue vulnerability. Unplanned urbanization and population growth, as observed in Acre during the period of study, contribute to ideal conditions for Ae. aegypti mosquito establishment, increase the difficulty in mosquito control and consequently its local receptivity.",2017 Nov 17,"['Lana, Raquel Martins', 'Gomes, Marcelo Ferreira da Costa', 'de Lima, Tiago França Melo', 'Honório, Nildimar Alves', 'Codeço, Cláudia Torres']",PLoS Negl Trop Dis,,,True
070e8dea105c31573755de6486b0948dd40972cc,PMC,"The introduction of dengue follows transportation infrastructure changes in the state of Acre, Brazil: A network-based analysis",http://dx.doi.org/10.1371/journal.pntd.0006070,PMC5693297,29149175,CC BY,"Human mobility, presence and passive transportation of Aedes aegypti mosquito, and environmental characteristics are a group of factors which contribute to the success of dengue spread and establishment. To understand this process, we assess data from dengue national and municipal basins regarding population and demographics, transportation network, human mobility, and Ae. aegypti monitoring for the Brazilian state of Acre since the first recorded dengue case in the year 2000 to the year 2015. During this period, several changes in Acre’s transport infrastructure and urbanization have been started. To reconstruct the process of dengue introduction in Acre, we propose an analytic framework based on concepts used in malaria literature, namely vulnerability and receptivity, to inform risk assessments in dengue-free regions as well as network theory concepts for disease invasion and propagation. We calculate the probability of dengue importation to Acre from other Brazilian states, the evolution of dengue spread between Acrean municipalities and dengue establishment in the state. Our findings suggest that the landscape changes associated with human mobility have created favorable conditions for the establishment of dengue virus transmission in Acre. The revitalization of its major roads, as well as the increased accessibility by air to and within the state, have increased dengue vulnerability. Unplanned urbanization and population growth, as observed in Acre during the period of study, contribute to ideal conditions for Ae. aegypti mosquito establishment, increase the difficulty in mosquito control and consequently its local receptivity.",2017 Nov 17,"['Lana, Raquel Martins', 'Gomes, Marcelo Ferreira da Costa', 'de Lima, Tiago França Melo', 'Honório, Nildimar Alves', 'Codeço, Cláudia Torres']",PLoS Negl Trop Dis,,,False
30d48d96ec3e25423861587cfc4c04bb3ae300cb,PMC,"The introduction of dengue follows transportation infrastructure changes in the state of Acre, Brazil: A network-based analysis",http://dx.doi.org/10.1371/journal.pntd.0006070,PMC5693297,29149175,CC BY,"Human mobility, presence and passive transportation of Aedes aegypti mosquito, and environmental characteristics are a group of factors which contribute to the success of dengue spread and establishment. To understand this process, we assess data from dengue national and municipal basins regarding population and demographics, transportation network, human mobility, and Ae. aegypti monitoring for the Brazilian state of Acre since the first recorded dengue case in the year 2000 to the year 2015. During this period, several changes in Acre’s transport infrastructure and urbanization have been started. To reconstruct the process of dengue introduction in Acre, we propose an analytic framework based on concepts used in malaria literature, namely vulnerability and receptivity, to inform risk assessments in dengue-free regions as well as network theory concepts for disease invasion and propagation. We calculate the probability of dengue importation to Acre from other Brazilian states, the evolution of dengue spread between Acrean municipalities and dengue establishment in the state. Our findings suggest that the landscape changes associated with human mobility have created favorable conditions for the establishment of dengue virus transmission in Acre. The revitalization of its major roads, as well as the increased accessibility by air to and within the state, have increased dengue vulnerability. Unplanned urbanization and population growth, as observed in Acre during the period of study, contribute to ideal conditions for Ae. aegypti mosquito establishment, increase the difficulty in mosquito control and consequently its local receptivity.",2017 Nov 17,"['Lana, Raquel Martins', 'Gomes, Marcelo Ferreira da Costa', 'de Lima, Tiago França Melo', 'Honório, Nildimar Alves', 'Codeço, Cláudia Torres']",PLoS Negl Trop Dis,,,False
2debdcb31159f7ce078114efcd6df551be4a0544,PMC,"The introduction of dengue follows transportation infrastructure changes in the state of Acre, Brazil: A network-based analysis",http://dx.doi.org/10.1371/journal.pntd.0006070,PMC5693297,29149175,CC BY,"Human mobility, presence and passive transportation of Aedes aegypti mosquito, and environmental characteristics are a group of factors which contribute to the success of dengue spread and establishment. To understand this process, we assess data from dengue national and municipal basins regarding population and demographics, transportation network, human mobility, and Ae. aegypti monitoring for the Brazilian state of Acre since the first recorded dengue case in the year 2000 to the year 2015. During this period, several changes in Acre’s transport infrastructure and urbanization have been started. To reconstruct the process of dengue introduction in Acre, we propose an analytic framework based on concepts used in malaria literature, namely vulnerability and receptivity, to inform risk assessments in dengue-free regions as well as network theory concepts for disease invasion and propagation. We calculate the probability of dengue importation to Acre from other Brazilian states, the evolution of dengue spread between Acrean municipalities and dengue establishment in the state. Our findings suggest that the landscape changes associated with human mobility have created favorable conditions for the establishment of dengue virus transmission in Acre. The revitalization of its major roads, as well as the increased accessibility by air to and within the state, have increased dengue vulnerability. Unplanned urbanization and population growth, as observed in Acre during the period of study, contribute to ideal conditions for Ae. aegypti mosquito establishment, increase the difficulty in mosquito control and consequently its local receptivity.",2017 Nov 17,"['Lana, Raquel Martins', 'Gomes, Marcelo Ferreira da Costa', 'de Lima, Tiago França Melo', 'Honório, Nildimar Alves', 'Codeço, Cláudia Torres']",PLoS Negl Trop Dis,,,False
d4f00f66c732c292fcfc28b19f44daa2fa620901,PMC,"Epidemiology and clinical profile of pathogens responsible for the hospitalization of children in Sousse area, Tunisia",http://dx.doi.org/10.1371/journal.pone.0188325,PMC5693464,29149199,CC BY,"This study aimed to identify a broad spectrum of respiratory pathogens from hospitalized and not-preselected children with acute respiratory tract infections in the Farhat Hached University-hospital of Sousse, Tunisia. Between September 2013 and December 2014, samples from 372 children aged between 1 month and 5 years were collected, and tested using multiplex real-time RT-PCR by a commercial assay for 21 respiratory pathogens. In addition, samples were screened for the presence of Streptococcus pneumoniae 16S rDNA using real-time PCR. The viral distribution and its association with clinical symptoms were statistically analyzed. Viral pathogens were detected in 342 (91.93%) of the samples of which 28.76% were single positive and 63.17% had multiple infections. The most frequent detected viruses were rhinovirus (55.64%), respiratory syncytial virus A/B (33.06%), adenovirus (25.00%), coronavirus NL63, HKU1, OC43, and 229E (21.50%), and metapneumovirus A/B (16.12%). Children in the youngest age group (1–3 months) exhibited the highest frequencies of infection. Related to their frequency of detection, RSV A/B was the most associated pathogen with patient’s demographic situation and clinical manifestations (p<0.05). Parainfluenza virus 1–4 and parechovirus were found to increase the risk of death (p<0.05). Adenovirus was statistically associated to the manifestation of gastroenteritis (p = 0.004). Rhinovirus infection increases the duration of oxygen support (p = 0.042). Coronavirus group was statistically associated with the manifestation of bronchiolitis (p = 0.009) and laryngitis (p = 0.017). Streptococcus pneumoniae DNA was detected in 143 (38.44%) of tested samples. However, only 53 samples had a concentration of C-reactive protein from equal to higher than 20 milligrams per liter, and 6 of them were single positive for Streptocuccus pneumoniae. This study confirms the high incidence of respiratory viruses in children hospitalized for acute respiratory tract infections in the Sousse area, Tunisia.",2017 Nov 17,"['Brini, Ines', 'Guerrero, Aida', 'Hannachi, Naila', 'Bouguila, Jihene', 'Orth-Höller, Dorothea', 'Bouhlel, Amira', 'Boughamoura, Lamia', 'Hetzer, Benjamin', 'Borena, Wegene', 'Schiela, Britta', 'Von Laer, Dorothee', 'Boukadida, Jalel', 'Stoiber, Heribert']",PLoS One,,,True
fef2fa32b0d64c8b71ce189e93679da45c5e4aad,PMC,"Epidemiology and clinical profile of pathogens responsible for the hospitalization of children in Sousse area, Tunisia",http://dx.doi.org/10.1371/journal.pone.0188325,PMC5693464,29149199,CC BY,"This study aimed to identify a broad spectrum of respiratory pathogens from hospitalized and not-preselected children with acute respiratory tract infections in the Farhat Hached University-hospital of Sousse, Tunisia. Between September 2013 and December 2014, samples from 372 children aged between 1 month and 5 years were collected, and tested using multiplex real-time RT-PCR by a commercial assay for 21 respiratory pathogens. In addition, samples were screened for the presence of Streptococcus pneumoniae 16S rDNA using real-time PCR. The viral distribution and its association with clinical symptoms were statistically analyzed. Viral pathogens were detected in 342 (91.93%) of the samples of which 28.76% were single positive and 63.17% had multiple infections. The most frequent detected viruses were rhinovirus (55.64%), respiratory syncytial virus A/B (33.06%), adenovirus (25.00%), coronavirus NL63, HKU1, OC43, and 229E (21.50%), and metapneumovirus A/B (16.12%). Children in the youngest age group (1–3 months) exhibited the highest frequencies of infection. Related to their frequency of detection, RSV A/B was the most associated pathogen with patient’s demographic situation and clinical manifestations (p<0.05). Parainfluenza virus 1–4 and parechovirus were found to increase the risk of death (p<0.05). Adenovirus was statistically associated to the manifestation of gastroenteritis (p = 0.004). Rhinovirus infection increases the duration of oxygen support (p = 0.042). Coronavirus group was statistically associated with the manifestation of bronchiolitis (p = 0.009) and laryngitis (p = 0.017). Streptococcus pneumoniae DNA was detected in 143 (38.44%) of tested samples. However, only 53 samples had a concentration of C-reactive protein from equal to higher than 20 milligrams per liter, and 6 of them were single positive for Streptocuccus pneumoniae. This study confirms the high incidence of respiratory viruses in children hospitalized for acute respiratory tract infections in the Sousse area, Tunisia.",2017 Nov 17,"['Brini, Ines', 'Guerrero, Aida', 'Hannachi, Naila', 'Bouguila, Jihene', 'Orth-Höller, Dorothea', 'Bouhlel, Amira', 'Boughamoura, Lamia', 'Hetzer, Benjamin', 'Borena, Wegene', 'Schiela, Britta', 'Von Laer, Dorothee', 'Boukadida, Jalel', 'Stoiber, Heribert']",PLoS One,,,False
423276fb8fbadb4e79c066d4fe8d121c308bc465,PMC,"Epidemiology and clinical profile of pathogens responsible for the hospitalization of children in Sousse area, Tunisia",http://dx.doi.org/10.1371/journal.pone.0188325,PMC5693464,29149199,CC BY,"This study aimed to identify a broad spectrum of respiratory pathogens from hospitalized and not-preselected children with acute respiratory tract infections in the Farhat Hached University-hospital of Sousse, Tunisia. Between September 2013 and December 2014, samples from 372 children aged between 1 month and 5 years were collected, and tested using multiplex real-time RT-PCR by a commercial assay for 21 respiratory pathogens. In addition, samples were screened for the presence of Streptococcus pneumoniae 16S rDNA using real-time PCR. The viral distribution and its association with clinical symptoms were statistically analyzed. Viral pathogens were detected in 342 (91.93%) of the samples of which 28.76% were single positive and 63.17% had multiple infections. The most frequent detected viruses were rhinovirus (55.64%), respiratory syncytial virus A/B (33.06%), adenovirus (25.00%), coronavirus NL63, HKU1, OC43, and 229E (21.50%), and metapneumovirus A/B (16.12%). Children in the youngest age group (1–3 months) exhibited the highest frequencies of infection. Related to their frequency of detection, RSV A/B was the most associated pathogen with patient’s demographic situation and clinical manifestations (p<0.05). Parainfluenza virus 1–4 and parechovirus were found to increase the risk of death (p<0.05). Adenovirus was statistically associated to the manifestation of gastroenteritis (p = 0.004). Rhinovirus infection increases the duration of oxygen support (p = 0.042). Coronavirus group was statistically associated with the manifestation of bronchiolitis (p = 0.009) and laryngitis (p = 0.017). Streptococcus pneumoniae DNA was detected in 143 (38.44%) of tested samples. However, only 53 samples had a concentration of C-reactive protein from equal to higher than 20 milligrams per liter, and 6 of them were single positive for Streptocuccus pneumoniae. This study confirms the high incidence of respiratory viruses in children hospitalized for acute respiratory tract infections in the Sousse area, Tunisia.",2017 Nov 17,"['Brini, Ines', 'Guerrero, Aida', 'Hannachi, Naila', 'Bouguila, Jihene', 'Orth-Höller, Dorothea', 'Bouhlel, Amira', 'Boughamoura, Lamia', 'Hetzer, Benjamin', 'Borena, Wegene', 'Schiela, Britta', 'Von Laer, Dorothee', 'Boukadida, Jalel', 'Stoiber, Heribert']",PLoS One,,,False
45673bc77a85f522c99ddfa23654813b570167bd,PMC,Peripheral immune tolerance alleviates the intracranial lipopolysaccharide injection-induced neuroinflammation and protects the dopaminergic neurons from neuroinflammation-related neurotoxicity,http://dx.doi.org/10.1186/s12974-017-0994-3,PMC5693474,29145874,CC BY,"BACKGROUND: Neuroinflammation plays a critical role in the onset and development of neurodegeneration disorders such as Parkinson’s disease. The immune activities of the central nervous system are profoundly affected by peripheral immune activities. Immune tolerance refers to the unresponsiveness of the immune system to continuous or repeated stimulation to avoid excessive inflammation and unnecessary by-stander injury in the face of continuous antigen threat. It has been proved that the immune tolerance could suppress the development of various peripheral inflammation-related diseases. However, the role of immune tolerance in neuroinflammation and neurodegenerative diseases was not clear. METHODS: Rats were injected with repeated low-dose lipopolysaccharide (LPS, 0.3 mg/kg) intraperitoneally for 4 days to induce peripheral immune tolerance. Neuroinflammation was produced using intracranial LPS (15 μg) injection. Inflammation cytokines were measured using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). Microglial activation were measured using immunostaining of Iba-1 and ED-1. Dopaminergic neuronal damage was evaluated using immunochemistry staining and stereological counting of TH-positive neurons. Behavioral impairment was evaluated using amphetamine-induced rotational behavioral assessment. RESULTS: Compared with the non-immune tolerated animals, pre-treatment of peripheral immune tolerance significantly decreased the production of inflammatory cytokines, suppressed the microglial activation, and increased the number of dopaminergic neuronal survival in the substantia nigra. CONCLUSIONS: Our results indicated that peripheral immune tolerance attenuated neuroinflammation and inhibited neuroinflammation-induced dopaminergic neuronal death. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-017-0994-3) contains supplementary material, which is available to authorized users.",2017 Nov 16,"['Liu, Yang', 'Xie, Xin', 'Xia, Li-Ping', 'Lv, Hong', 'Lou, Fan', 'Ren, Yan', 'He, Zhi-Yi', 'Luo, Xiao-Guang']",J Neuroinflammation,,,True
3341998ccda48a6464d056736f52a967b45df144,PMC,Putative progressive and abortive feline leukemia virus infection outcomes in captive jaguarundis (Puma yagouaroundi),http://dx.doi.org/10.1186/s12985-017-0889-z,PMC5693524,29149857,CC BY,"BACKGROUND: Feline leukemia virus (FeLV) is an exogenous gammaretrovirus of domestic cats (Felis catus) and some wild felids. The outcomes of FeLV infection in domestic cats vary according to host susceptibility, virus strain, and infectious challenge dose. Jaguarundis (Puma yagouaroundi) are small wild felids from South and Central America. We previously reported on FeLV infections in jaguarundis. We hypothesized here that the outcomes of FeLV infection in P. yagouaroundi mimic those observed in domestic cats. The aim of this study was to investigate the population of jaguarundis at Fundação Parque Zoológico de São Paulo for natural FeLV infection and resulting outcomes. METHODS: We investigated the jaguarundis using serological and molecular methods and monitored them for FeLV-related diseases for 5 years. We retrieved relevant biological and clinical information for the entire population of 23 jaguarundis held at zoo. Post-mortem findings from necropsies were recorded and histopathological and immunohistopathological analyses were performed. Sequencing and phylogenetic analyses were performed for FeLV-positive samples. For sample prevalence, 95% confidence intervals (CI) were calculated. Fisher’s exact test was used to compare frequencies between infected and uninfected animals. P-values <0.05 were considered significant. RESULTS: In total, we detected evidence of FeLV exposure in four out of 23 animals (17%; 95% CI 5–39%). No endogenous FeLV (enFeLV) sequences were detected. An intestinal B-cell lymphoma in one jaguarundi was not associated with FeLV. Two jaguarundis presented FeLV test results consistent with an abortive FeLV infection with seroconversion, and two other jaguarundis had results consistent with a progressive infection and potentially FeLV-associated clinical disorders and post-mortem changes. Phylogenetic analysis of env revealed the presence of FeLV-A, a common origin of the virus in both animals (100% identity) and the closest similarity to FeLV-FAIDS and FeLV-3281 (98.4% identity), originally isolated from cats in the USA. CONCLUSIONS: We found evidence of progressive and abortive FeLV infection outcomes in jaguarundis, and domestic cats were probably the source of infection in these jaguarundis.",2017 Nov 17,"['Filoni, Claudia', 'Helfer-Hungerbuehler, A. Katrin', 'Catão-Dias, José Luiz', 'Marques, Mara Cristina', 'Torres, Luciana Neves', 'Reinacher, Manfred', 'Hofmann-Lehmann, Regina']",Virol J,,,True
4ea66e72fc7ed0902b973ab0fc9993aab3d4e4cb,PMC,The global spread of Middle East respiratory syndrome: an analysis fusing traditional epidemiological tracing and molecular phylodynamics,http://dx.doi.org/10.1186/s41256-016-0014-7,PMC5693564,29202063,CC BY,"BACKGROUND: Since its discovery in 2012, over 1700 confirmed cases of Middle East Respiratory Syndrome (MERS) have been documented worldwide and more than a third of those cases have died. While the greatest number of cases has occurred in Saudi Arabia, the recent export of MERS-coronavirus (MERS-CoV) to Republic of Korea showed that a pandemic is a possibility that cannot be ignored. Due to the deficit of knowledge in transmission methodology, targeted treatment and possible vaccines, understanding this virus should be a priority. Our aim was to combine epidemiological data from literature with genetic information from viruses sequenced around the world to present a phylodynamic picture of MERS spread molecular level to global scale. METHODS: We performed a qualitative meta-analysis of all laboratory confirmed cases worldwide to date based on literature, with emphasis on international transmission and healthcare associated infections. In parallel, we used publicly available MERS-CoV genomes from GenBank to create a phylogeographic tree, detailing geospatial timeline of viral evolution. RESULTS: Several healthcare associated outbreaks starting with the retrospectively identified hospital outbreak in Jordan to the most recent outbreak in Riyadh, Saudi Arabia have occurred. MERS has also crossed many oceans, entering multiple nations in eight waves between 2012 and 2015. In this paper, the spatiotemporal history of MERS cases, as documented epidemiologically, was examined by Bayesian phylogenetic analysis. Distribution of sequences into geographic clusters and interleaving of MERS-CoV sequences from camels among those isolated from humans indicated that multiple zoonotic introductions occurred in endemic nations. We also report a summary of basic reproduction numbers for MERS-CoV in humans and camels. CONCLUSION: Together, these analyses can help us identify factors associated with viral evolution and spread as well as establish efficacy of infection control measures. The results are especially pertinent to countries without current MERS-CoV endemic, since their unfamiliarity makes them particularly susceptible to uncontrollable spread of a virus that may be imported by travelers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s41256-016-0014-7) contains supplementary material, which is available to authorized users.",2016 Sep 28,"['Min, Jae', 'Cella, Eleonora', 'Ciccozzi, Massimo', 'Pelosi, Antonello', 'Salemi, Marco', 'Prosperi, Mattia']",Glob Health Res Policy,,,True
a89a80a592e5af122545d57ff70bc683d28831e8,PMC,Innate Immunity to Respiratory Infection in Early Life,http://dx.doi.org/10.3389/fimmu.2017.01570,PMC5694434,29184555,CC BY,"Early life is a period of particular susceptibility to respiratory infections and symptoms are frequently more severe in infants than in adults. The neonatal immune system is generally held to be deficient in most compartments; responses to innate stimuli are weak, antigen-presenting cells have poor immunostimulatory activity and adaptive lymphocyte responses are limited, leading to poor immune memory and ineffective vaccine responses. For mucosal surfaces such as the lung, which is continuously exposed to airborne antigen and to potential pathogenic invasion, the ability to discriminate between harmless and potentially dangerous antigens is essential, to prevent inflammation that could lead to loss of gaseous exchange and damage to the developing lung tissue. We have only recently begun to define the differences in respiratory immunity in early life and its environmental and developmental influences. The innate immune system may be of relatively greater importance than the adaptive immune system in the neonatal and infant period than later in life, as it does not require specific antigenic experience. A better understanding of what constitutes protective innate immunity in the respiratory tract in this age group and the factors that influence its development should allow us to predict why certain infants are vulnerable to severe respiratory infections, design treatments to accelerate the development of protective immunity, and design age specific adjuvants to better boost immunity to infection in the lung.",2017 Nov 14,"['Lambert, Laura', 'Culley, Fiona J.']",Front Immunol,,,True
899c5959f51505b0935e46c2e77129156026806e,PMC,Establishment and evaluation of a theater influenza monitoring platform,http://dx.doi.org/10.1186/s40779-017-0144-3,PMC5694910,29502518,CC BY,"BACKGROUND: Influenza is an acute respiratory infectious disease with a high incidence rate in the Chinese army, which directly disturbs military training and affects soldiers’ health. Influenza surveillance systems are widely used around the world and play an important role in influenza epidemic prevention and control. METHODS: As a theater centers for disease prevention and control, we established an influenza monitoring platform (IMP) in 2014 to strengthen the monitoring of influenza-like illness and influenza virus infection. In this study, we introduced the constitution, influenza virus detection, and quality control for an IMP. The monitoring effect was also evaluated by comparing the monitoring data with data from national influenza surveillance systems. The experiences and problems associated with the platform also were summarized. RESULTS: A theater IMP was established based on 3 levels of medical units, including monitoring sites, testing laboratories and a checking laboratory. A series of measures were taken to guarantee the quality of monitoring, such as technical training, a unified process, sufficient supervision and timely communication. The platform has run smoothly for 3 monitoring years to date. In the 2014–2015 and 2016–2017 monitoring years, sample amount coincided with that obtained from the National Influenza Surveillance program. In the 2015–2016 monitoring year, due to the strict prevention and control measures, an influenza epidemic peak was avoided in monitoring units, and the monitoring data did not coincide with that of the National Influenza Surveillance program. Several problems, including insufficient attention, unreasonable administrative intervention or subordination relationships, and the necessity of detection in monitoring sites were still observed. CONCLUSIONS: A theater IMP was established rationally and played a deserved role in the prevention and control of influenza. However, several problems remain to be solved.",2017 Nov 20,"['Wang, Jian', 'Yang, Hui-Suo', 'Deng, Bing', 'Shi, Meng-Jing', 'Li, Xiang-Da', 'Nian, Qing-Gong', 'Song, Wen-Jing', 'Bing, Feng', 'Li, Qing-Feng']",Mil Med Res,,,True
714370d75af9d91c8812733f732d98ddfff8074a,PMC,"Field-deployable, quantitative, rapid identification of active Ebola virus infection in unprocessed blood",http://dx.doi.org/10.1039/c7sc03281a,PMC5694917,29163915,CC BY,"The West African Ebola virus outbreak underlined the importance of delivering mass diagnostic capability outside the clinical or primary care setting in effectively containing public health emergencies caused by infectious disease. Yet, to date, there is no solution for reliably deploying at the point of need the gold standard diagnostic method, real time quantitative reverse transcription polymerase chain reaction (RT-qPCR), in a laboratory infrastructure-free manner. In this proof of principle work, we demonstrate direct performance of RT-qPCR on fresh blood using far-red fluorophores to resolve fluorogenic signal inhibition and controlled, rapid freeze/thawing to achieve viral genome extraction in a single reaction chamber assay. The resulting process is entirely free of manual or automated sample pre-processing, requires no microfluidics or magnetic/mechanical sample handling and thus utilizes low cost consumables. This enables a fast, laboratory infrastructure-free, minimal risk and simple standard operating procedure suited to frontline, field use. Developing this novel approach on recombinant bacteriophage and recombinant human immunodeficiency virus (HIV; Lentivirus), we demonstrate clinical utility in symptomatic EBOV patient screening using live, infectious Filoviruses and surrogate patient samples. Moreover, we evidence assay co-linearity independent of viral particle structure that may enable viral load quantification through pre-calibration, with no loss of specificity across an 8 log-linear maximum dynamic range. The resulting quantitative rapid identification (QuRapID) molecular diagnostic platform, openly accessible for assay development, meets the requirements of resource-limited countries and provides a fast response solution for mass public health screening against emerging biosecurity threats.",2017 Nov 1,"['Shah, Kavit', 'Bentley, Emma', 'Tyler, Adam', 'Richards, Kevin S. R.', 'Wright, Edward', 'Easterbrook, Linda', 'Lee, Diane', 'Cleaver, Claire', 'Usher, Louise', 'Burton, Jane E.', 'Pitman, James K.', 'Bruce, Christine B.', 'Edge, David', 'Lee, Martin', 'Nazareth, Nelson', 'Norwood, David A.', 'Moschos, Sterghios A.']",Chem Sci,,,True
b4c9dee0b34c6c9349f3f951e8d028331be205d2,PMC,"Field-deployable, quantitative, rapid identification of active Ebola virus infection in unprocessed blood",http://dx.doi.org/10.1039/c7sc03281a,PMC5694917,29163915,CC BY,"The West African Ebola virus outbreak underlined the importance of delivering mass diagnostic capability outside the clinical or primary care setting in effectively containing public health emergencies caused by infectious disease. Yet, to date, there is no solution for reliably deploying at the point of need the gold standard diagnostic method, real time quantitative reverse transcription polymerase chain reaction (RT-qPCR), in a laboratory infrastructure-free manner. In this proof of principle work, we demonstrate direct performance of RT-qPCR on fresh blood using far-red fluorophores to resolve fluorogenic signal inhibition and controlled, rapid freeze/thawing to achieve viral genome extraction in a single reaction chamber assay. The resulting process is entirely free of manual or automated sample pre-processing, requires no microfluidics or magnetic/mechanical sample handling and thus utilizes low cost consumables. This enables a fast, laboratory infrastructure-free, minimal risk and simple standard operating procedure suited to frontline, field use. Developing this novel approach on recombinant bacteriophage and recombinant human immunodeficiency virus (HIV; Lentivirus), we demonstrate clinical utility in symptomatic EBOV patient screening using live, infectious Filoviruses and surrogate patient samples. Moreover, we evidence assay co-linearity independent of viral particle structure that may enable viral load quantification through pre-calibration, with no loss of specificity across an 8 log-linear maximum dynamic range. The resulting quantitative rapid identification (QuRapID) molecular diagnostic platform, openly accessible for assay development, meets the requirements of resource-limited countries and provides a fast response solution for mass public health screening against emerging biosecurity threats.",2017 Nov 1,"['Shah, Kavit', 'Bentley, Emma', 'Tyler, Adam', 'Richards, Kevin S. R.', 'Wright, Edward', 'Easterbrook, Linda', 'Lee, Diane', 'Cleaver, Claire', 'Usher, Louise', 'Burton, Jane E.', 'Pitman, James K.', 'Bruce, Christine B.', 'Edge, David', 'Lee, Martin', 'Nazareth, Nelson', 'Norwood, David A.', 'Moschos, Sterghios A.']",Chem Sci,,,False
4f4a156d0bc65afd5d8f5b80b4bb8436a590955a,PMC,Spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia,http://dx.doi.org/10.1371/journal.pone.0188251,PMC5695780,29155867,CC BY,"Pneumonia may be caused by a wide range of pathogens and is considered the most common infectious cause of death in humans. Murine acute lung infection models mirror human pathologies in many aspects and contribute to our understanding of the disease and the development of novel treatment strategies. Despite progress in other fields of tissue imaging, histopathology remains the most conclusive and practical read out tool for the descriptive and semiquantitative evaluation of mouse pneumonia and therapeutic interventions. Here, we systematically describe and compare the distinctive histopathological features of established models of acute pneumonia in mice induced by Streptococcus (S.) pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Legionella pneumophila, Escherichia coli, Middle East respiratory syndrome (MERS) coronavirus, influenza A virus (IAV) and superinfection of IAV-incuced pneumonia with S. pneumoniae. Systematic comparisons of the models revealed striking differences in the distribution of lesions, the characteristics of pneumonia induced, principal inflammatory cell types, lesions in adjacent tissues, and the detectability of the pathogens in histological sections. We therefore identified core criteria for each model suitable for practical semiquantitative scoring systems that take into account the pathogen- and model-specific patterns of pneumonia. Other critical factors that affect experimental pathologies are discussed, including infectious dose, time kinetics, and the genetic background of the mouse strain. The substantial differences between the model-specific pathologies underscore the necessity of pathogen- and model-adapted criteria for the comparative quantification of experimental outcomes. These criteria also allow for the standardized validation and comparison of treatment strategies in preclinical models.",2017 Nov 20,"['Dietert, Kristina', 'Gutbier, Birgitt', 'Wienhold, Sandra M.', 'Reppe, Katrin', 'Jiang, Xiaohui', 'Yao, Ling', 'Chaput, Catherine', 'Naujoks, Jan', 'Brack, Markus', 'Kupke, Alexandra', 'Peteranderl, Christin', 'Becker, Stephan', 'von Lachner, Carolin', 'Baal, Nelli', 'Slevogt, Hortense', 'Hocke, Andreas C.', 'Witzenrath, Martin', 'Opitz, Bastian', 'Herold, Susanne', 'Hackstein, Holger', 'Sander, Leif E.', 'Suttorp, Norbert', 'Gruber, Achim D.']",PLoS One,,,True
01a462bf8cf2cd973d1651b991d27c9556d2ae3c,PMC,A mobile loop near the active site acts as a switch between the dual activities of a viral protease/deubiquitinase,http://dx.doi.org/10.1371/journal.ppat.1006714,PMC5695851,29117247,CC BY,"The positive-strand RNA virus Turnip yellow mosaic virus (TYMV) encodes an ovarian tumor (OTU)-like protease/deubiquitinase (PRO/DUB) protein domain involved both in proteolytic processing of the viral polyprotein through its PRO activity, and in removal of ubiquitin chains from ubiquitylated substrates through its DUB activity. Here, the crystal structures of TYMV PRO/DUB mutants and molecular dynamics simulations reveal that an idiosyncratic mobile loop participates in reversibly constricting its unusual catalytic site by adopting ""open"", ""intermediate"" or ""closed"" conformations. The two cis-prolines of the loop form a rigid flap that in the most closed conformation zips up against the other side of the catalytic cleft. The intermediate and closed conformations also correlate with a reordering of the TYMV PRO/DUB catalytic dyad, that then assumes a classical, yet still unusually mobile, OTU DUB alignment. Further structure-based mutants designed to interfere with the loop's mobility were assessed for enzymatic activity in vitro and in vivo, and were shown to display reduced DUB activity while retaining PRO activity. This indicates that control of the switching between the dual PRO/DUB activities resides prominently within this loop next to the active site. Introduction of mutations into the viral genome revealed that the DUB activity contributes to the extent of viral RNA accumulation both in single cells and in whole plants. In addition, the conformation of the mobile flap was also found to influence symptoms severity in planta. Such mutants now provide powerful tools with which to study the specific roles of reversible ubiquitylation in viral infection.",2017 Nov 8,"['Jupin, Isabelle', 'Ayach, Maya', 'Jomat, Lucile', 'Fieulaine, Sonia', 'Bressanelli, Stéphane']",PLoS Pathog,,,True
c8df0fd2c7d06947d2bb15ebed6ce0bad831b297,PMC,Computational design of fully overlapping coding schemes for protein pairs and triplets,http://dx.doi.org/10.1038/s41598-017-16221-8,PMC5696523,29158504,CC BY,"Gene pairs that overlap in their coding regions are rare except in viruses. They may occur transiently in gene creation and are of biotechnological interest. We have examined the possibility to encode an arbitrary pair of protein domains as a dual gene, with the shorter coding sequence completely embedded in the longer one. For 500 × 500 domain pairs (X, Y), we computationally designed homologous pairs (X′, Y′) coded this way, using an algorithm that provably maximizes the sequence similarity between (X′, Y′) and (X, Y). Three schemes were considered, with X′ and Y′ coded on the same or complementary strands. For 16% of the pairs, an overlapping coding exists where the level of homology of X′, Y′ to the natural proteins represents an E-value of 10(−10) or better. Thus, for an arbitrary domain pair, it is surprisingly easy to design homologous sequences that can be encoded as a fully-overlapping gene pair. The algorithm is general and was used to design 200 triple genes, with three proteins encoded by the same DNA segment. The ease of design suggests overlapping genes may have occurred frequently in evolution and could be readily used to compress or constrain artificial genomes.",2017 Nov 20,"['Opuu, Vaitea', 'Silvert, Martin', 'Simonson, Thomas']",Sci Rep,,,True
9c492e76efc05b17e67a3e09c7e3ac44cca89e29,PMC,Coinfection with Haemophilus parasuis serovar 4 increases the virulence of porcine circovirus type 2 in piglets,http://dx.doi.org/10.1186/s12985-017-0890-6,PMC5696968,29157279,CC BY,"BACKGROUND: Postweaning multisystemic wasting syndrome (PMWS) is an emerging disease in swine. Pigs with PMWS are often infected with a variety of other pathogens, including bacteria, viruses and mycoplasm, in addition to porcine circovirus type 2 (PCV2). PCV2 and Haemophilus parasuis serovar 4 (HPS4) coinfection remain epidemic in China. METHODS: Here we report construction of a three-week-old naturally farrowed, colostrum-deprived (NFCD) piglet’s infection model and demonstrate that PCV2-infected piglets with the HPS4 coinfection increased the virulence of PCV2 and these pathogens interact acquired PMWS. RESULTS: All the single infected piglets were transiently bacteremic or viremic. All the PCV2/HPS4 coinfected piglets developed PMWS, characterized by dyspnea, anorexia, prostration and lose weight severely. Co-infection with PCV2 and HPS4 resulted in an increased amount of virus in serum and tissues, presented a slower generation and lower levels of antibodies against PCV2. Co-infection with PCV2 and HPS4 resulted in further reductions in total and differential peripheral blood leukocyte counts. Meantime, PCV2/ HPS4 coinfection potentiated the severity of lung and lymphoid lesions by PCV2-associated, increased the virulence of PCV2-antigen and enhanced the incidence of PMWS in piglets. CONCLUSION: Co-infection with PCV2 and HPS4 induce the exacerbation of system injuries and enhance the pathogenicity of PCV2 in piglets.",2017 Nov 21,"['Liu, Shuqing', 'Li, Wentao', 'Wang, Yang', 'Gu, Changqin', 'Liu, Xiaoli', 'Charreyre, Catherine', 'Fan, Shenxian', 'He, Qigai']",Virol J,,,True
617ec397b4376957e6d055f1989e66b158b93f1a,PMC,More than meets the I: the diverse antiviral and cellular functions of interferon-induced transmembrane proteins,http://dx.doi.org/10.1186/s12977-017-0377-y,PMC5697417,29162141,CC BY,"The first responders of human antiviral immunity are components of the intrinsic immune response that reside within each and every one of our cells. This cell-autonomous arsenal consists of nucleic acid sensors and antiviral effectors strategically placed by evolution to detect and restrict invading viruses. While some factors are present at baseline to allow for constant surveillance of the cell interior, others are upregulated by cytokines (such as interferons) that signal a viral infection underway in neighboring cells. In this review, we highlight the multiple roles played by the interferon-induced transmembrane (IFITM) proteins during viral infection, with focuses on IFITM3 and HIV-1. Moreover, we discuss the cellular pathways in which IFITM proteins are intertwined and the various functions they have been ascribed outside the context of infection. While appreciated as broadly-acting, potent restriction factors that prevent virus infection and pathogenesis in cell culture and in vivo, questions remain regarding their precise mode of action and importance in certain viral contexts. Continued efforts to study IFITM protein function will further cement their status as critical host determinants of virus susceptibility and prioritize them in the development of new antiviral therapies.",2017 Nov 21,"['Shi, Guoli', 'Schwartz, Olivier', 'Compton, Alex A.']",Retrovirology,,,True
5be812ecd3a63e7b5e718f17d9ca3a0d0fdb4a70,PMC,Spatiotemporal dynamics of HSV genome nuclear entry and compaction state transitions using bioorthogonal chemistry and super-resolution microscopy,http://dx.doi.org/10.1371/journal.ppat.1006721,PMC5697887,29121649,CC BY,"We investigated the spatiotemporal dynamics of HSV genome transport during the initiation of infection using viruses containing bioorthogonal traceable precursors incorporated into their genomes (HSV(EdC)). In vitro assays revealed a structural alteration in the capsid induced upon HSV(EdC) binding to solid supports that allowed coupling to external capture agents and demonstrated that the vast majority of individual virions contained bioorthogonally-tagged genomes. Using HSV(EdC) in vivo we reveal novel aspects of the kinetics, localisation, mechanistic entry requirements and morphological transitions of infecting genomes. Uncoating and nuclear import was observed within 30 min, with genomes in a defined compaction state (ca. 3-fold volume increase from capsids). Free cytosolic uncoated genomes were infrequent (7–10% of the total uncoated genomes), likely a consequence of subpopulations of cells receiving high particle numbers. Uncoated nuclear genomes underwent temporal transitions in condensation state and while ICP4 efficiently associated with condensed foci of initial infecting genomes, this relationship switched away from residual longer lived condensed foci to increasingly decondensed genomes as infection progressed. Inhibition of transcription had no effect on nuclear entry but in the absence of transcription, genomes persisted as tightly condensed foci. Ongoing transcription, in the absence of protein synthesis, revealed a distinct spatial clustering of genomes, which we have termed genome congregation, not seen with non-transcribing genomes. Genomes expanded to more decondensed forms in the absence of DNA replication indicating additional transitional steps. During full progression of infection, genomes decondensed further, with a diffuse low intensity signal dissipated within replication compartments, but frequently with tight foci remaining peripherally, representing unreplicated genomes or condensed parental strands of replicated DNA. Uncoating and nuclear entry was independent of proteasome function and resistant to inhibitors of nuclear export. Together with additional data our results reveal new insight into the spatiotemporal dynamics of HSV genome uncoating, transport and organisation.",2017 Nov 9,"['Sekine, Eiki', 'Schmidt, Nora', 'Gaboriau, David', 'O’Hare, Peter']",PLoS Pathog,,,True
cb7bbade2083d71f793469f51b908363e9f25cbd,PMC,Broad-spectrum antiviral agents: secreted phospholipase A(2) targets viral envelope lipid bilayers derived from the endoplasmic reticulum membrane,http://dx.doi.org/10.1038/s41598-017-16130-w,PMC5698466,29162867,CC BY,"Hepatitis C virus (HCV), dengue virus (DENV) and Japanese encephalitis virus (JEV) belong to the family Flaviviridae. Their viral particles have the envelope composed of viral proteins and a lipid bilayer acquired from budding through the endoplasmic reticulum (ER). The phospholipid content of the ER membrane differs from that of the plasma membrane (PM). The phospholipase A(2) (PLA(2)) superfamily consists of a large number of members that specifically catalyse the hydrolysis of phospholipids at a particular position. Here we show that the CM-II isoform of secreted PLA(2) obtained from Naja mossambica mossambica snake venom (CM-II-sPLA(2)) possesses potent virucidal (neutralising) activity against HCV, DENV and JEV, with 50% inhibitory concentrations (IC(50)) of 0.036, 0.31 and 1.34 ng/ml, respectively. In contrast, the IC(50) values of CM-II-sPLA(2) against viruses that bud through the PM (Sindbis virus, influenza virus and Sendai virus) or trans-Golgi network (TGN) (herpes simplex virus) were >10,000 ng/ml. Moreover, the 50% cytotoxic (CC(50)) and haemolytic (HC(50)) concentrations of CM-II-sPLA(2) were >10,000 ng/ml, implying that CM-II-sPLA(2) did not significantly damage the PM. These results suggest that CM-II-sPLA(2) and its derivatives are good candidates for the development of broad-spectrum antiviral drugs that target viral envelope lipid bilayers derived from the ER membrane.",2017 Nov 21,"['Chen, Ming', 'Aoki-Utsubo, Chie', 'Kameoka, Masanori', 'Deng, Lin', 'Terada, Yutaka', 'Kamitani, Wataru', 'Sato, Kei', 'Koyanagi, Yoshio', 'Hijikata, Makoto', 'Shindo, Keiko', 'Noda, Takeshi', 'Kohara, Michinori', 'Hotta, Hak']",Sci Rep,,,False
b894fde1276ea66d0eef9ecf55b025adc58f105d,PMC,Broad-spectrum antiviral agents: secreted phospholipase A(2) targets viral envelope lipid bilayers derived from the endoplasmic reticulum membrane,http://dx.doi.org/10.1038/s41598-017-16130-w,PMC5698466,29162867,CC BY,"Hepatitis C virus (HCV), dengue virus (DENV) and Japanese encephalitis virus (JEV) belong to the family Flaviviridae. Their viral particles have the envelope composed of viral proteins and a lipid bilayer acquired from budding through the endoplasmic reticulum (ER). The phospholipid content of the ER membrane differs from that of the plasma membrane (PM). The phospholipase A(2) (PLA(2)) superfamily consists of a large number of members that specifically catalyse the hydrolysis of phospholipids at a particular position. Here we show that the CM-II isoform of secreted PLA(2) obtained from Naja mossambica mossambica snake venom (CM-II-sPLA(2)) possesses potent virucidal (neutralising) activity against HCV, DENV and JEV, with 50% inhibitory concentrations (IC(50)) of 0.036, 0.31 and 1.34 ng/ml, respectively. In contrast, the IC(50) values of CM-II-sPLA(2) against viruses that bud through the PM (Sindbis virus, influenza virus and Sendai virus) or trans-Golgi network (TGN) (herpes simplex virus) were >10,000 ng/ml. Moreover, the 50% cytotoxic (CC(50)) and haemolytic (HC(50)) concentrations of CM-II-sPLA(2) were >10,000 ng/ml, implying that CM-II-sPLA(2) did not significantly damage the PM. These results suggest that CM-II-sPLA(2) and its derivatives are good candidates for the development of broad-spectrum antiviral drugs that target viral envelope lipid bilayers derived from the ER membrane.",2017 Nov 21,"['Chen, Ming', 'Aoki-Utsubo, Chie', 'Kameoka, Masanori', 'Deng, Lin', 'Terada, Yutaka', 'Kamitani, Wataru', 'Sato, Kei', 'Koyanagi, Yoshio', 'Hijikata, Makoto', 'Shindo, Keiko', 'Noda, Takeshi', 'Kohara, Michinori', 'Hotta, Hak']",Sci Rep,,,True
b6365c84be3efb9b6845cf8f664ae3e5b913c4a0,PMC,Expression and Cleavage of Middle East Respiratory Syndrome Coronavirus nsp3-4 Polyprotein Induce the Formation of Double-Membrane Vesicles That Mimic Those Associated with Coronaviral RNA Replication,http://dx.doi.org/10.1128/mBio.01658-17,PMC5698553,29162711,CC BY,"Betacoronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV), are important pathogens causing potentially lethal infections in humans and animals. Coronavirus RNA synthesis is thought to be associated with replication organelles (ROs) consisting of modified endoplasmic reticulum (ER) membranes. These are transformed into double-membrane vesicles (DMVs) containing viral double-stranded RNA and into other membranous elements such as convoluted membranes, together forming a reticulovesicular network. Previous evidence suggested that the nonstructural proteins (nsp’s) 3, 4, and 6 of the severe acute respiratory syndrome coronavirus (SARS-CoV), which contain transmembrane domains, would all be required for DMV formation. We have now expressed MERS-CoV replicase self-cleaving polyprotein fragments encompassing nsp3-4 or nsp3-6, as well as coexpressed nsp3 and nsp4 of either MERS-CoV or SARS-CoV, to characterize the membrane structures induced. Using electron tomography, we demonstrate that for both MERS-CoV and SARS-CoV coexpression of nsp3 and nsp4 is required and sufficient to induce DMVs. Coexpression of MERS-CoV nsp3 and nsp4 either as individual proteins or as a self-cleaving nsp3-4 precursor resulted in very similar DMVs, and in both setups we observed proliferation of zippered ER that appeared to wrap into nascent DMVs. Moreover, when inactivating nsp3-4 polyprotein cleavage by mutagenesis, we established that cleavage of the nsp3/nsp4 junction is essential for MERS-CoV DMV formation. Addition of the third MERS-CoV transmembrane protein, nsp6, did not noticeably affect DMV formation. These findings provide important insight into the biogenesis of coronavirus DMVs, establish strong similarities with other nidoviruses (specifically, the arteriviruses), and highlight possible general principles in viral DMV formation.",2017 Nov 21,"['Oudshoorn, Diede', 'Rijs, Kevin', 'Limpens, Ronald W. A. L.', 'Groen, Kevin', 'Koster, Abraham J.', 'Snijder, Eric J.', 'Kikkert, Marjolein', 'Bárcena, Montserrat']",mBio,,,True
79233a0dcabd313110b3256113778d814f7bc902,PMC,An unfolded protein-induced conformational switch activates mammalian IRE1,http://dx.doi.org/10.7554/eLife.30700,PMC5699868,28971800,CC BY,"The unfolded protein response (UPR) adjusts the cell’s protein folding capacity in the endoplasmic reticulum (ER) according to need. IRE1 is the most conserved UPR sensor in eukaryotic cells. It has remained controversial, however, whether mammalian and yeast IRE1 use a common mechanism for ER stress sensing. Here, we show that similar to yeast, human IRE1α’s ER-lumenal domain (hIRE1α LD) binds peptides with a characteristic amino acid bias. Peptides and unfolded proteins bind to hIRE1α LD’s MHC-like groove and induce allosteric changes that lead to its oligomerization. Mutation of a hydrophobic patch at the oligomerization interface decoupled peptide binding to hIRE1α LD from its oligomerization, yet retained peptide-induced allosteric coupling within the domain. Importantly, impairing oligomerization of hIRE1α LD abolished IRE1’s activity in living cells. Our results provide evidence for a unifying mechanism of IRE1 activation that relies on unfolded protein binding-induced oligomerization.",,"['Karagöz, G Elif', 'Acosta-Alvear, Diego', 'Nguyen, Hieu T', 'Lee, Crystal P', 'Chu, Feixia', 'Walter, Peter']",eLife.; 6:e30700,,,True
e7d2a577433aca44d525181d8378d7d12a72d0b3,PMC,An unfolded protein-induced conformational switch activates mammalian IRE1,http://dx.doi.org/10.7554/eLife.30700,PMC5699868,28971800,CC BY,"The unfolded protein response (UPR) adjusts the cell’s protein folding capacity in the endoplasmic reticulum (ER) according to need. IRE1 is the most conserved UPR sensor in eukaryotic cells. It has remained controversial, however, whether mammalian and yeast IRE1 use a common mechanism for ER stress sensing. Here, we show that similar to yeast, human IRE1α’s ER-lumenal domain (hIRE1α LD) binds peptides with a characteristic amino acid bias. Peptides and unfolded proteins bind to hIRE1α LD’s MHC-like groove and induce allosteric changes that lead to its oligomerization. Mutation of a hydrophobic patch at the oligomerization interface decoupled peptide binding to hIRE1α LD from its oligomerization, yet retained peptide-induced allosteric coupling within the domain. Importantly, impairing oligomerization of hIRE1α LD abolished IRE1’s activity in living cells. Our results provide evidence for a unifying mechanism of IRE1 activation that relies on unfolded protein binding-induced oligomerization.",,"['Karagöz, G Elif', 'Acosta-Alvear, Diego', 'Nguyen, Hieu T', 'Lee, Crystal P', 'Chu, Feixia', 'Walter, Peter']",eLife.; 6:e30700,,,False
ed97726670ebbd9bda6b9c855234513bccca919f,PMC,Clinical and virological factors associated with gastrointestinal symptoms in patients with acute respiratory infection: a two-year prospective study in general practice medicine,http://dx.doi.org/10.1186/s12879-017-2823-9,PMC5700681,29166867,CC BY,"BACKGROUND: Gastrointestinal (GI) symptoms, such as diarrhea, vomiting, abdominal pain and nausea are not an uncommon manifestation of an acute respiratory infection (ARI). We therefore evaluated clinical and microbiological factors associated with the presence of GI symptoms in patients consulting a general practitioner (GP) for ARI. METHODS: Nasopharyngeal swabs, stool specimens and clinical data from patients presenting to GPs with an ARI were prospectively collected during two winter seasons (2014-2016). Samples were tested by quantitative real-time PCR for 12 respiratory pathogen groups and for 12 enteric pathogens. RESULTS: Two hundred and four of 331 included patients (61.6%) were positive for at least one respiratory pathogen. Sixty-nine stools (20.8%) were positive for at least one pathogen (respiratory and/or enteric). GI symptoms were more likely declared in case of laboratory confirmed-enteric infection (adjusted odds ratio (aOR) = 3.2; 95% confidence interval [CI] [1.2–9.9]; p = 0.02) or human coronavirus (HCoV) infection (aOR = 2.7; [1.2–6.8]; p = 0.02). Consumption of antipyretic medication before the consultation seemed to reduce the risk of developing GI symptoms for patients with laboratory-confirmed influenza (aOR = 0.3; [0.1–0.6]; p = 0.002). CONCLUSIONS: The presence of GI symptoms in ARI patients could not be explained by the detection of respiratory pathogens in stools. However, the detection of enteric pathogens in stool samples could explained by the presence of GI symptoms in some of ARI cases. The biological mechanisms explaining the association between the presence of HCoVs in nasopharynx and GI symptoms need to be explored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-017-2823-9) contains supplementary material, which is available to authorized users.",2017 Nov 22,"['Minodier, Laetitia', 'Masse, Shirley', 'Capai, Lisandru', 'Blanchon, Thierry', 'Ceccaldi, Pierre-Emmanuel', 'van der Werf, Sylvie', 'Hanslik, Thomas', 'Charrel, Remi', 'Falchi, Alessandra']",BMC Infect Dis,,,False
7e94b71efcbef73a7a5c90a73322e31e504e3aa3,PMC,Clinical and virological factors associated with gastrointestinal symptoms in patients with acute respiratory infection: a two-year prospective study in general practice medicine,http://dx.doi.org/10.1186/s12879-017-2823-9,PMC5700681,29166867,CC BY,"BACKGROUND: Gastrointestinal (GI) symptoms, such as diarrhea, vomiting, abdominal pain and nausea are not an uncommon manifestation of an acute respiratory infection (ARI). We therefore evaluated clinical and microbiological factors associated with the presence of GI symptoms in patients consulting a general practitioner (GP) for ARI. METHODS: Nasopharyngeal swabs, stool specimens and clinical data from patients presenting to GPs with an ARI were prospectively collected during two winter seasons (2014-2016). Samples were tested by quantitative real-time PCR for 12 respiratory pathogen groups and for 12 enteric pathogens. RESULTS: Two hundred and four of 331 included patients (61.6%) were positive for at least one respiratory pathogen. Sixty-nine stools (20.8%) were positive for at least one pathogen (respiratory and/or enteric). GI symptoms were more likely declared in case of laboratory confirmed-enteric infection (adjusted odds ratio (aOR) = 3.2; 95% confidence interval [CI] [1.2–9.9]; p = 0.02) or human coronavirus (HCoV) infection (aOR = 2.7; [1.2–6.8]; p = 0.02). Consumption of antipyretic medication before the consultation seemed to reduce the risk of developing GI symptoms for patients with laboratory-confirmed influenza (aOR = 0.3; [0.1–0.6]; p = 0.002). CONCLUSIONS: The presence of GI symptoms in ARI patients could not be explained by the detection of respiratory pathogens in stools. However, the detection of enteric pathogens in stool samples could explained by the presence of GI symptoms in some of ARI cases. The biological mechanisms explaining the association between the presence of HCoVs in nasopharynx and GI symptoms need to be explored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-017-2823-9) contains supplementary material, which is available to authorized users.",2017 Nov 22,"['Minodier, Laetitia', 'Masse, Shirley', 'Capai, Lisandru', 'Blanchon, Thierry', 'Ceccaldi, Pierre-Emmanuel', 'van der Werf, Sylvie', 'Hanslik, Thomas', 'Charrel, Remi', 'Falchi, Alessandra']",BMC Infect Dis,,,False
2e47652d940fa99656ba24f45c45f75731400a0e,PMC,Clinical and virological factors associated with gastrointestinal symptoms in patients with acute respiratory infection: a two-year prospective study in general practice medicine,http://dx.doi.org/10.1186/s12879-017-2823-9,PMC5700681,29166867,CC BY,"BACKGROUND: Gastrointestinal (GI) symptoms, such as diarrhea, vomiting, abdominal pain and nausea are not an uncommon manifestation of an acute respiratory infection (ARI). We therefore evaluated clinical and microbiological factors associated with the presence of GI symptoms in patients consulting a general practitioner (GP) for ARI. METHODS: Nasopharyngeal swabs, stool specimens and clinical data from patients presenting to GPs with an ARI were prospectively collected during two winter seasons (2014-2016). Samples were tested by quantitative real-time PCR for 12 respiratory pathogen groups and for 12 enteric pathogens. RESULTS: Two hundred and four of 331 included patients (61.6%) were positive for at least one respiratory pathogen. Sixty-nine stools (20.8%) were positive for at least one pathogen (respiratory and/or enteric). GI symptoms were more likely declared in case of laboratory confirmed-enteric infection (adjusted odds ratio (aOR) = 3.2; 95% confidence interval [CI] [1.2–9.9]; p = 0.02) or human coronavirus (HCoV) infection (aOR = 2.7; [1.2–6.8]; p = 0.02). Consumption of antipyretic medication before the consultation seemed to reduce the risk of developing GI symptoms for patients with laboratory-confirmed influenza (aOR = 0.3; [0.1–0.6]; p = 0.002). CONCLUSIONS: The presence of GI symptoms in ARI patients could not be explained by the detection of respiratory pathogens in stools. However, the detection of enteric pathogens in stool samples could explained by the presence of GI symptoms in some of ARI cases. The biological mechanisms explaining the association between the presence of HCoVs in nasopharynx and GI symptoms need to be explored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-017-2823-9) contains supplementary material, which is available to authorized users.",2017 Nov 22,"['Minodier, Laetitia', 'Masse, Shirley', 'Capai, Lisandru', 'Blanchon, Thierry', 'Ceccaldi, Pierre-Emmanuel', 'van der Werf, Sylvie', 'Hanslik, Thomas', 'Charrel, Remi', 'Falchi, Alessandra']",BMC Infect Dis,,,False
23904278d806ced4d6fd0ea9b264d495562cf7e1,PMC,Clinical and virological factors associated with gastrointestinal symptoms in patients with acute respiratory infection: a two-year prospective study in general practice medicine,http://dx.doi.org/10.1186/s12879-017-2823-9,PMC5700681,29166867,CC BY,"BACKGROUND: Gastrointestinal (GI) symptoms, such as diarrhea, vomiting, abdominal pain and nausea are not an uncommon manifestation of an acute respiratory infection (ARI). We therefore evaluated clinical and microbiological factors associated with the presence of GI symptoms in patients consulting a general practitioner (GP) for ARI. METHODS: Nasopharyngeal swabs, stool specimens and clinical data from patients presenting to GPs with an ARI were prospectively collected during two winter seasons (2014-2016). Samples were tested by quantitative real-time PCR for 12 respiratory pathogen groups and for 12 enteric pathogens. RESULTS: Two hundred and four of 331 included patients (61.6%) were positive for at least one respiratory pathogen. Sixty-nine stools (20.8%) were positive for at least one pathogen (respiratory and/or enteric). GI symptoms were more likely declared in case of laboratory confirmed-enteric infection (adjusted odds ratio (aOR) = 3.2; 95% confidence interval [CI] [1.2–9.9]; p = 0.02) or human coronavirus (HCoV) infection (aOR = 2.7; [1.2–6.8]; p = 0.02). Consumption of antipyretic medication before the consultation seemed to reduce the risk of developing GI symptoms for patients with laboratory-confirmed influenza (aOR = 0.3; [0.1–0.6]; p = 0.002). CONCLUSIONS: The presence of GI symptoms in ARI patients could not be explained by the detection of respiratory pathogens in stools. However, the detection of enteric pathogens in stool samples could explained by the presence of GI symptoms in some of ARI cases. The biological mechanisms explaining the association between the presence of HCoVs in nasopharynx and GI symptoms need to be explored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-017-2823-9) contains supplementary material, which is available to authorized users.",2017 Nov 22,"['Minodier, Laetitia', 'Masse, Shirley', 'Capai, Lisandru', 'Blanchon, Thierry', 'Ceccaldi, Pierre-Emmanuel', 'van der Werf, Sylvie', 'Hanslik, Thomas', 'Charrel, Remi', 'Falchi, Alessandra']",BMC Infect Dis,,,True
c890cb0b691543c29b35b5a1351ff8c990739fe2,PMC,Prevalence and genetic diversity analysis of human coronaviruses among cross-border children,http://dx.doi.org/10.1186/s12985-017-0896-0,PMC5700739,29166910,CC BY,"BACKGROUND: More than a decade after the outbreak of human coronaviruses (HCoVs) SARS in Guangdong province and Hong Kong SAR of China in 2002, there is still no reoccurrence, but the evolution and recombination of the coronaviruses in this region are still unknown. Therefore, surveillance on the prevalence and the virus variation of HCoVs circulation in this region is conducted. METHODS: A total of 3298 nasopharyngeal swabs samples were collected from cross-border children (<6 years, crossing border between Southern China and Hong Kong SAR) showing symptoms of respiratory tract infection, such as fever (body temperature > 37.5 °C), from 2014 May to 2015 Dec. Viral nucleic acids were analyzed and sequenced to study the prevalence and genetic diversity of the four human coronaviruses. The statistical significance of the data was evaluated with Fisher chi-square test. RESULTS: 78 (2.37%; 95%CI 1.8-2.8%) out of 3298 nasopharyngeal swabs specimens were found to be positive for OC43 (36;1.09%), HKU1 (34; 1.03%), NL63 (6; 0.18%) and 229E (2;0.01%). None of SARS or MERS was detected. The HCoVs predominant circulating season was in transition of winter to spring, especially January and February and NL63 detected only in summer and fall. Complex population with an abundant genetic diversity of coronaviruses was circulating and they shared homology with the published strains (99-100%). Besides, phylogenetic evolutionary analysis indicated that OC43 coronaviruses were clustered into three clades (B,D,E), HKU1 clustered into two clades(A,B) and NL63 clustered into two clades(A,B). Moreover, several novel mutations including nucleotides substitution and the insertion of spike of the glycoprotein on the viral surface were discovered. CONCLUSIONS: The detection rate and epidemic trend of coronaviruses were stable and no obvious fluctuations were found. The detected coronaviruses shared a conserved gene sequences in S and RdRp. However, mutants of the epidemic strains were detected, suggesting continuous monitoring of the human coronaviruses is in need among cross-border children, who are more likely to get infected and transmit the viruses across the border easily, in addition to the general public.",2017 Nov 22,"['Liu, Peilin', 'Shi, Lei', 'Zhang, Wei', 'He, Jianan', 'Liu, Chunxiao', 'Zhao, Chunzhong', 'Kong, Siu Kai', 'Loo, Jacky Fong Chuen', 'Gu, Dayong', 'Hu, Longfei']",Virol J,,,True
e501f519aa1c6206d331d587dee9454f17038876,PMC,Receptor-binding loops in alphacoronavirus adaptation and evolution,http://dx.doi.org/10.1038/s41467-017-01706-x,PMC5701055,29170370,CC BY,"RNA viruses are characterized by a high mutation rate, a buffer against environmental change. Nevertheless, the means by which random mutation improves viral fitness is not well characterized. Here we report the X-ray crystal structure of the receptor-binding domain (RBD) of the human coronavirus, HCoV-229E, in complex with the ectodomain of its receptor, aminopeptidase N (APN). Three extended loops are solely responsible for receptor binding and the evolution of HCoV-229E and its close relatives is accompanied by changing loop–receptor interactions. Phylogenetic analysis shows that the natural HCoV-229E receptor-binding loop variation observed defines six RBD classes whose viruses have successively replaced each other in the human population over the past 50 years. These RBD classes differ in their affinity for APN and their ability to bind an HCoV-229E neutralizing antibody. Together, our results provide a model for alphacoronavirus adaptation and evolution based on the use of extended loops for receptor binding.",2017 Nov 23,"['Wong, Alan H. M.', 'Tomlinson, Aidan C. A.', 'Zhou, Dongxia', 'Satkunarajah, Malathy', 'Chen, Kevin', 'Sharon, Chetna', 'Desforges, Marc', 'Talbot, Pierre J.', 'Rini, James M.']",Nat Commun,,,False
560a8d3105b38de8fcec9a4e9a65e6ac8649aad1,PMC,Receptor-binding loops in alphacoronavirus adaptation and evolution,http://dx.doi.org/10.1038/s41467-017-01706-x,PMC5701055,29170370,CC BY,"RNA viruses are characterized by a high mutation rate, a buffer against environmental change. Nevertheless, the means by which random mutation improves viral fitness is not well characterized. Here we report the X-ray crystal structure of the receptor-binding domain (RBD) of the human coronavirus, HCoV-229E, in complex with the ectodomain of its receptor, aminopeptidase N (APN). Three extended loops are solely responsible for receptor binding and the evolution of HCoV-229E and its close relatives is accompanied by changing loop–receptor interactions. Phylogenetic analysis shows that the natural HCoV-229E receptor-binding loop variation observed defines six RBD classes whose viruses have successively replaced each other in the human population over the past 50 years. These RBD classes differ in their affinity for APN and their ability to bind an HCoV-229E neutralizing antibody. Together, our results provide a model for alphacoronavirus adaptation and evolution based on the use of extended loops for receptor binding.",2017 Nov 23,"['Wong, Alan H. M.', 'Tomlinson, Aidan C. A.', 'Zhou, Dongxia', 'Satkunarajah, Malathy', 'Chen, Kevin', 'Sharon, Chetna', 'Desforges, Marc', 'Talbot, Pierre J.', 'Rini, James M.']",Nat Commun,,,False
13b976db365e4973e7e0fe44646393b672c4a2db,PMC,Receptor-binding loops in alphacoronavirus adaptation and evolution,http://dx.doi.org/10.1038/s41467-017-01706-x,PMC5701055,29170370,CC BY,"RNA viruses are characterized by a high mutation rate, a buffer against environmental change. Nevertheless, the means by which random mutation improves viral fitness is not well characterized. Here we report the X-ray crystal structure of the receptor-binding domain (RBD) of the human coronavirus, HCoV-229E, in complex with the ectodomain of its receptor, aminopeptidase N (APN). Three extended loops are solely responsible for receptor binding and the evolution of HCoV-229E and its close relatives is accompanied by changing loop–receptor interactions. Phylogenetic analysis shows that the natural HCoV-229E receptor-binding loop variation observed defines six RBD classes whose viruses have successively replaced each other in the human population over the past 50 years. These RBD classes differ in their affinity for APN and their ability to bind an HCoV-229E neutralizing antibody. Together, our results provide a model for alphacoronavirus adaptation and evolution based on the use of extended loops for receptor binding.",2017 Nov 23,"['Wong, Alan H. M.', 'Tomlinson, Aidan C. A.', 'Zhou, Dongxia', 'Satkunarajah, Malathy', 'Chen, Kevin', 'Sharon, Chetna', 'Desforges, Marc', 'Talbot, Pierre J.', 'Rini, James M.']",Nat Commun,,,True
ce74ed47b12de8d1c70b2cac843b6953c57bd5de,PMC,Complete Genome Sequence of Human Coronavirus Strain 229E Isolated from Plasma Collected from a Haitian Child in 2016,http://dx.doi.org/10.1128/genomeA.01313-17,PMC5701476,29167251,CC BY,"Human coronavirus strain 229E (HCoV-229E) and human alphaherpesvirus 1 were isolated from the plasma of a Haitian child in 2016 with suspected arbovirus diseases. To our knowledge, this is the first description of HCoV-229E in human plasma, which is the focus of this article.",2017 Nov 22,"['Bonny, Tania S.', 'Subramaniam, Kuttichantran', 'Waltzek, Thomas B.', 'Elbadry, Maha A.', 'Beau De Rochars, Valery Madsen', 'Telisma, Taina', 'Rashid, Mohammed', 'Morris, J. Glenn', 'Lednicky, John A.']",Genome Announc,,,True
a25efe46f5c7aed65e0abf4fb1d487ba5a30d4cd,PMC,Transcriptome analysis of avian reovirus-mediated changes in gene expression of normal chicken fibroblast DF-1 cells,http://dx.doi.org/10.1186/s12864-017-4310-5,PMC5702118,29178824,CC BY,"BACKGROUND: Avian reovirus (ARV) is an important poultry pathogen that can cause immunosuppression. In this study, RNA-Seq technology was applied to investigate the transcriptome-wide changes of DF-1 cells upon ARV infection at the middle stage. RESULTS: Total RNA of ARV-infected or mock-infected samples at 10 and 18 h post infection (hpi) was extracted to build RNA-Seq datasets. Analysis of the sequencing data revealed that the expressions of numerous genes were altered, and a panel of differentially expressed genes were confirmed with RT-qPCR. At 10 hpi, 104 genes were down-regulated and 64 were up-regulated, while the expressions of 47 genes were increased and only one was down-regulated, which may play a role in retinoic acid biosynthesis, at 18 hpi in the ARV-infected cells. The similar profiles of up-regulated genes between the two groups of infected cells suggest that ARV infection activated a prolonged antiviral response of host cells. Alternative splicing analysis found no significantly changed events altered by ARV infection. CONCLUSIONS: Overall, the differential expression profile presented in this study can be used to expand our understanding of the comprehensive interactions between ARV and the host cells, and may be helpful for us to reveal the pathogenic mechanism on the molecular level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-017-4310-5) contains supplementary material, which is available to authorized users.",2017 Nov 25,"['Niu, Xiaosai', 'Wang, Yuyang', 'Li, Min', 'Zhang, Xiaorong', 'Wu, Yantao']",BMC Genomics,,,False
602fbb4e85804b8ca5c0842b46afd343981181e4,PMC,Transcriptome analysis of avian reovirus-mediated changes in gene expression of normal chicken fibroblast DF-1 cells,http://dx.doi.org/10.1186/s12864-017-4310-5,PMC5702118,29178824,CC BY,"BACKGROUND: Avian reovirus (ARV) is an important poultry pathogen that can cause immunosuppression. In this study, RNA-Seq technology was applied to investigate the transcriptome-wide changes of DF-1 cells upon ARV infection at the middle stage. RESULTS: Total RNA of ARV-infected or mock-infected samples at 10 and 18 h post infection (hpi) was extracted to build RNA-Seq datasets. Analysis of the sequencing data revealed that the expressions of numerous genes were altered, and a panel of differentially expressed genes were confirmed with RT-qPCR. At 10 hpi, 104 genes were down-regulated and 64 were up-regulated, while the expressions of 47 genes were increased and only one was down-regulated, which may play a role in retinoic acid biosynthesis, at 18 hpi in the ARV-infected cells. The similar profiles of up-regulated genes between the two groups of infected cells suggest that ARV infection activated a prolonged antiviral response of host cells. Alternative splicing analysis found no significantly changed events altered by ARV infection. CONCLUSIONS: Overall, the differential expression profile presented in this study can be used to expand our understanding of the comprehensive interactions between ARV and the host cells, and may be helpful for us to reveal the pathogenic mechanism on the molecular level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-017-4310-5) contains supplementary material, which is available to authorized users.",2017 Nov 25,"['Niu, Xiaosai', 'Wang, Yuyang', 'Li, Min', 'Zhang, Xiaorong', 'Wu, Yantao']",BMC Genomics,,,True
0e536891c4d89b74cea0ed4788fc8e3bff5a6787,PMC,Trypsin-independent porcine epidemic diarrhea virus US strain with altered virus entry mechanism,http://dx.doi.org/10.1186/s12917-017-1283-1,PMC5702120,29178878,CC BY,"BACKGROUND: Porcine Epidemic Diarrhea Virus (PEDV) is a coronavirus that infects the intestinal tract and causes diarrhea and vomiting in older pigs or extreme dehydration and death that could reach 100% mortality in neonatal piglets. In the US, the first PEDV outbreaks occurred in 2013 and since then US PEDV strains have quickly spread throughout the US and worldwide, causing significant economic and public health concerns. Currently two conditionally approved vaccines exist in the US, but there is no live attenuated vaccine, which is considered the best option in controlling PEDV by inducing transferrable mucosal immunity to susceptible neonatal piglets. In this study, we passaged an US PEDV isolate under various conditions to generate three strains and characterized their growth and antigenicity in cell culture using various assays including Western blot analysis, serum neutralization assay, sequencing analysis and confocal microscopy. Finally, these strains were evaluated for pathogenicity in nursing piglets (1–4 days old). RESULTS: One of the PEDV strains generated in this study (designated as PEDV 8aa) is able to replicate in cells without any protease and grows to a high titer of >8 log(10) TCID(50)/ml in cell culture. Interestingly, replication of PEDV 8aa was severely reduced by trypsin and this correlated with the inhibition of virus attachment and entry into the cells. In neonatal nursing piglets, PEDV 8aa (passage number 70 or 105) was found to be fully attenuated with limited virus shedding. CONCLUSIONS: These results suggest that applying selective pressure during viral passages can facilitate attainment of viral attenuation and that PEDV 8aa warrants further investigation as an attenuated vaccine.",2017 Nov 25,"['Kim, Yunjeong', 'Oh, Changin', 'Shivanna, Vinay', 'Hesse, Richard A.', 'Chang, Kyeong-Ok']",BMC Vet Res,,,True
dda902a72728faf3f12e96b6765ed4beb0b57961,PMC,"Perturbation of Wound Healing, Cytoskeletal Organization and Cellular Protein Networks during Hazara Virus Infection",http://dx.doi.org/10.3389/fcell.2017.00098,PMC5702460,29209610,CC BY,"Normal epithelial and endothelial renewal and healing after bacterial and viral challenges are essential for homeostasis along the intestine and the blood and lymphatic vessels. We thus investigated whether and how virus affects migration of human epithelial cells and specifically how the nucleocapsid protein (N) modulates the cellular proteome and interactome using human Caco-2 cells in a wound-healing assay with Hazara virus as a model. Here, Hazara virus blocked cell migration in a dose- and time-dependent manner, disrupted the actin cytoskeleton and specifically reduced the expression of the IQ-motif-containing GTPase-activating protein 1 (IQGAP1) and water channel aquaporin 6 (AQP6) that regulate cytoskeletal organization, water homeostasis and vesicle communication. Moreover, in the Caco-2 cell proteome, we identified several distinct groups of molecules associating with N upon Hazara virus infection, being involved in the ensemble of important cellular processes, e.g., chaperone activity, metabolism, cellular defense against infections, cell morphology, and migration. These events do not only facilitate the virus life cycle, but they are also crucial for membrane and cytoskeleton dynamics, cellular self-renewal and wound healing, being so essential for body integrity and homeostasis.",2017 Nov 21,"['Molinas, Andrea', 'Turkina, Maria V.', 'Magnusson, Karl-Eric', 'Mirazimi, Ali', 'Vikström, Elena']",Front Cell Dev Biol,,,True
84f5fad8c5f0702b6816a479ae152a2dd58fa7f4,PMC,Intensifying poultry production systems and the emergence of avian influenza in China: a ‘One Health/Ecohealth’ epitome,http://dx.doi.org/10.1186/s13690-017-0218-4,PMC5702979,29209498,CC BY,"Several kinds of pressure can lead to the emergence of infectious diseases. In the case of zoonoses emerging from livestock, one of the most significant changes that has taken place since the mid twentieth century is what has been termed the “livestock revolution”, whereby the stock of food animals, their productivity and their trade has increased rapidly to feed rising and increasingly wealthy and urbanized populations. Further increases are projected in the future in low and middle-income countries. Using avian influenza as an example, we discuss how the emergence of avian influenza H5N1 and H7N9 in China was linked to rapid intensification of the poultry sector taking place in landscapes rich in wetland agriculture and wild waterfowls habitats, providing an extensive interface with the wild reservoir of avian influenza viruses. Trade networks and live-poultry markets further exacerbated the spread and persistence of avian influenza as well as human exposure. However, as the history of emergence of highly pathogenic avian influenza (HPAI) demonstrates in high-income countries such as the USA, Canada, Australia, the United Kingdom or the Netherlands, this is by no way specific to low and middle-income countries. Many HPAI emergence events took place in countries with generally good biosecurity standards, and the majority of these in regions hosting intensive poultry production systems. Emerging zoonoses are only one of a number of externalities of intensive livestock production systems, alongside antimicrobial consumption, disruption of nutrient cycles and greenhouse gases emissions, with direct or indirect impacts on human health. In parallel, livestock production is essential to nutrition and livelihoods in many low-income countries. Deindustrialization of the most intensive production systems in high-income countries and sustainable intensifications in low-income countries may converge to a situation where the nutritional and livelihood benefits of livestock production would be less overshadowed by its negative impacts on human an ecosystem health.",2017 Nov 27,"['Gilbert, Marius', 'Xiao, Xiangming', 'Robinson, Timothy P.']",Arch Public Health,,,True
422cd9eb3c56e4f05ba9ced4ecbda48bdc043c16,PMC,Effectiveness of composting as a biosecure disposal method for porcine epidemic diarrhea virus (PEDV)-infected pig carcasses,http://dx.doi.org/10.1186/s40813-017-0068-z,PMC5704383,29209511,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is an enteric disease of swine that has emerged as a worldwide threat to swine herd health and production. Substantial research has been conducted to assess viability of the virus on surfaces of vehicles and equipment, in feed and water, and on production building surfaces, but little is known about the persistence in PEDV-infected carcasses and effective disposal methods thereof. This study was conducted to quantify the persistence of PEDV RNA via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) at various time-temperature combinations and in infected piglet carcasses subjected to composting. Although this method does not distinguish between infectious and noninfectious virus, it is a rapid and sensitive test to evaluate materials for evidence of virus genome. RESULTS: In the first study, PEDV was suspended in cell culture media at 1 × 10(5) TCID50 per sample (1 mL sample size) and subjected to various time and temperature combinations in triplicate including temperatures of 37, 45, 50, 55, 60, 65, 70 °C and exposure times of 0, 1, 2, 3, 4, 5, 7, and 14 days. At all temperatures, viral RNA copies declined over time, with the decline most marked and rapid at 65 and 70 °C. Detectable RNA did persist throughout the trial in all but the most extreme condition, where two of three samples incubated at 70 °C yielded undetectable viral RNA after 14 days. In the second study, PEDV-infected piglet carcasses were subjected to two cycles of composting lasting 36 and 37 days, respectively, for a total compost time of 73 days. Composting was performed in triplicate windrow sections housed inside biosecure, climate-controlled rooms using insulated bins designed to represent a continuous windrow compost pile. Temperatures reached 35–57 °C for 26 days of cycle 1 and 35–45 °C for 3 days of cycle 2. Samples consisting of carbon material with or without decomposed tissue as available per sample site collected at ten locations throughout the cross-section of each windrow section following the primary and secondary compost cycles yielded no detectable viral RNA. CONCLUSIONS: Composting appears to be an effective disposal method for PEDV-infected piglet carcasses under the conditions examined. The combination of time and high temperature of the compost cycle effectively degraded viral RNA in cell culture media that should provide optimum stability. Complex compost material matrices collected from windrow sections yielded undetectable PEDV RNA by qRT-PCR after one 36-day compost cycle despite incomplete decomposition of soft tissue.",2017 Nov 28,"['Vitosh-Sillman, Sarah', 'Loy, John Dustin', 'Brodersen, Bruce', 'Kelling, Clayton', 'Eskridge, Kent', 'Millmier Schmidt, Amy']",Porcine Health Manag,,,True
89d81992f625da155c5f9e0ea869ea6e53577936,PMC,Intrinsically disordered sequences enable modulation of protein phase separation through distributed tyrosine motifs,http://dx.doi.org/10.1074/jbc.M117.800466,PMC5704491,28924037,CC BY,"Liquid–liquid phase separation (LLPS) is thought to contribute to the establishment of many biomolecular condensates, eukaryotic cell structures that concentrate diverse macromolecules but lack a bounding membrane. RNA granules control RNA metabolism and comprise a large class of condensates that are enriched in RNA-binding proteins and RNA molecules. Many RNA granule proteins are composed of both modular domains and intrinsically disordered regions (IDRs) having low amino acid sequence complexity. Phase separation of these molecules likely plays an important role in the generation and stability of RNA granules. To understand how folded domains and IDRs can cooperate to modulate LLPS, we generated a series of engineered proteins. These were based on fusions of an IDR derived from the RNA granule protein FUS (fused in sarcoma) to a multivalent poly-Src homology 3 (SH3) domain protein that phase-separates when mixed with a poly-proline–rich-motif (polyPRM) ligand. We found that the wild-type IDR promotes LLPS of the polySH3–polyPRM system, decreasing the phase separation threshold concentration by 8-fold. Systematic mutation of tyrosine residues in Gly/Ser-Tyr-Gly/Ser motifs of the IDR reduced this effect, depending on the number but not on the position of these substitutions. Mutating all tyrosines to non-aromatic residues or phosphorylating the IDR raised the phase separation threshold above that of the unmodified polySH3–polyPRM pair. These results show that low-complexity IDRs can modulate LLPS both positively and negatively, depending on the degree of aromaticity and phosphorylation status. Our findings provide plausible mechanisms by which these sequences could alter RNA granule properties on evolutionary and cellular timescales.",2017 Nov 17,"['Lin, Yuan', 'Currie, Simon L.', 'Rosen, Michael K.']",J Biol Chem,,,False
17ef76b6acdc223229e3a6ed236bed4c2fc0f811,PMC,Intrinsically disordered sequences enable modulation of protein phase separation through distributed tyrosine motifs,http://dx.doi.org/10.1074/jbc.M117.800466,PMC5704491,28924037,CC BY,"Liquid–liquid phase separation (LLPS) is thought to contribute to the establishment of many biomolecular condensates, eukaryotic cell structures that concentrate diverse macromolecules but lack a bounding membrane. RNA granules control RNA metabolism and comprise a large class of condensates that are enriched in RNA-binding proteins and RNA molecules. Many RNA granule proteins are composed of both modular domains and intrinsically disordered regions (IDRs) having low amino acid sequence complexity. Phase separation of these molecules likely plays an important role in the generation and stability of RNA granules. To understand how folded domains and IDRs can cooperate to modulate LLPS, we generated a series of engineered proteins. These were based on fusions of an IDR derived from the RNA granule protein FUS (fused in sarcoma) to a multivalent poly-Src homology 3 (SH3) domain protein that phase-separates when mixed with a poly-proline–rich-motif (polyPRM) ligand. We found that the wild-type IDR promotes LLPS of the polySH3–polyPRM system, decreasing the phase separation threshold concentration by 8-fold. Systematic mutation of tyrosine residues in Gly/Ser-Tyr-Gly/Ser motifs of the IDR reduced this effect, depending on the number but not on the position of these substitutions. Mutating all tyrosines to non-aromatic residues or phosphorylating the IDR raised the phase separation threshold above that of the unmodified polySH3–polyPRM pair. These results show that low-complexity IDRs can modulate LLPS both positively and negatively, depending on the degree of aromaticity and phosphorylation status. Our findings provide plausible mechanisms by which these sequences could alter RNA granule properties on evolutionary and cellular timescales.",2017 Nov 17,"['Lin, Yuan', 'Currie, Simon L.', 'Rosen, Michael K.']",J Biol Chem,,,True
98f15c53c23507e24cf28eeaf7e097a099bdce2b,PMC,"Estimating the incubation period of hand, foot and mouth disease for children in different age groups",http://dx.doi.org/10.1038/s41598-017-16705-7,PMC5705633,29184105,CC BY,"Hand, foot and mouth disease (HFMD) is a childhood disease causing large outbreaks frequently in Asia and occasionally in Europe and the US. The incubation period of HFMD was typically described as about 3–7 days but empirical evidence is lacking. In this study, we estimated the incubation period of HFMD from school outbreaks in Hong Kong, utilizing information on symptom onset and sick absence dates of students diagnosed with HFMD. A total of 99 HFMD cases from 12 schools were selected for analysis. We fitted parametric models accounting for interval censoring. Based on the best-fitted distributions, the estimated median incubation periods were 4.4 (95% CI 3.8–5.1) days, 4.7 (95% CI 4.5–5.1) days and 5.7 (95% CI 4.6–7.0) days for children in kindergartens, primary schools and secondary schools respectively. From the fitted distribution, the estimated incubation periods can be longer than 10 days for 8.8% and 23.2% of the HFMD cases in kindergarten and secondary schools respectively. Our results show that the incubation period of HFMD for secondary schools students can be longer than the ranges commonly described. An extended period of enhanced personal hygiene practice and disinfection of the environment may be needed to control outbreaks.",2017 Nov 28,"['Yang, Zhongzhou', 'Zhang, Qiqi', 'Cowling, Benjamin J.', 'Lau, Eric H. Y.']",Sci Rep,,,False
9f63dea0f76ee477d2e8e5209d40179db431ab1d,PMC,"Estimating the incubation period of hand, foot and mouth disease for children in different age groups",http://dx.doi.org/10.1038/s41598-017-16705-7,PMC5705633,29184105,CC BY,"Hand, foot and mouth disease (HFMD) is a childhood disease causing large outbreaks frequently in Asia and occasionally in Europe and the US. The incubation period of HFMD was typically described as about 3–7 days but empirical evidence is lacking. In this study, we estimated the incubation period of HFMD from school outbreaks in Hong Kong, utilizing information on symptom onset and sick absence dates of students diagnosed with HFMD. A total of 99 HFMD cases from 12 schools were selected for analysis. We fitted parametric models accounting for interval censoring. Based on the best-fitted distributions, the estimated median incubation periods were 4.4 (95% CI 3.8–5.1) days, 4.7 (95% CI 4.5–5.1) days and 5.7 (95% CI 4.6–7.0) days for children in kindergartens, primary schools and secondary schools respectively. From the fitted distribution, the estimated incubation periods can be longer than 10 days for 8.8% and 23.2% of the HFMD cases in kindergarten and secondary schools respectively. Our results show that the incubation period of HFMD for secondary schools students can be longer than the ranges commonly described. An extended period of enhanced personal hygiene practice and disinfection of the environment may be needed to control outbreaks.",2017 Nov 28,"['Yang, Zhongzhou', 'Zhang, Qiqi', 'Cowling, Benjamin J.', 'Lau, Eric H. Y.']",Sci Rep,,,True
c3bef1c075c76c313a27542f3aa138c48b1c5d3d,PMC,"Human parainfluenza virus infection in severe acute respiratory infection cases in Beijing, 2014‐2016: A molecular epidemiological study",http://dx.doi.org/10.1111/irv.12514,PMC5705688,29054112,CC BY,"BACKGROUND: Severe acute respiratory infection (SARI) threatens human health and even survival, causing a huge number of hospitalized patients every year. However, as one of the most common respiratory viruses circulated worldwide, the epidemiological and phylogenetic characteristics of human parainfluenza virus (HPIV) in these cases were not well known. OBJECTIVES: To reveal the epidemiological features of HPIV infection in SARIs in Beijing area from September 2014 to August 2016. METHODS: A total of 1229 SARI cases in Beijing area were enrolled, investigated, sampled, and tested by multiplex real‐time PCR to identify HPIVs and other common respiratory viruses. Eighteen HPIV‐3 viruses isolated from all HPIV‐positive samples in these SARI cases were sequenced and analyzed. RESULTS: Among all enrolled cases, 0.81%, 0.73%, 4.48%, and 0.57% were positive for HPIV‐1 to HPIV‐4, respectively. The highest yield rate of HPIV infection occurred in children under 5 years old (9.07%), followed by the patients over 60 years old (6.02%). The phylogenetic information of HPIV‐3 showed that all viruses belonged to Cluster C3a. CONCLUSIONS: Besides the young children, the elders older than 60 years also showed a relatively high infection rate of HPIVs, which should be given comparable attentions. Moreover, the HPIV‐3 circulating in China undergoes continued evolution, suggesting the potential risk of evolved HPIV infection should not be overlooked.",2017 Nov 28,"['Pan, Yang', 'Zhang, Yi', 'Shi, Weixian', 'Peng, Xiaomin', 'Cui, Shujuan', 'Zhang, Daitao', 'Lu, Guilan', 'Liu, Yimeng', 'Wu, Shuangsheng', 'Yang, Peng', 'Wang, Quanyi']",Influenza Other Respir Viruses,,,True
b56db50e2116c867bbc86aefcdfec72c74e971ed,PMC,The efficacy of medical masks and respirators against respiratory infection in healthcare workers,http://dx.doi.org/10.1111/irv.12474,PMC5705692,28799710,CC BY,"OBJECTIVE: We aimed to examine the efficacy of medical masks and respirators in protecting against respiratory infections using pooled data from two homogenous randomised control clinical trials (RCTs). METHODS: The data collected on 3591 subjects in two similar RCTs conducted in Beijing, China, which examined the same infection outcomes, were pooled. Four interventions were compared: (i) continuous N95 respirator use, (ii) targeted N95 respirator use, (iii) medical mask use and (iv) control arm. The outcomes were laboratory‐confirmed viral respiratory infection, influenza A or B, laboratory‐confirmed bacterial colonisation and pathogens grouped by mode of transmission. RESULTS: Rates of all outcomes were consistently lower in the continuous N95 and/or targeted N95 arms. In adjusted analysis, rates of laboratory‐confirmed bacterial colonisation (RR 0.33, 95% CI 0.21‐0.51), laboratory‐confirmed viral infections (RR 0.46, 95% CI 0.23‐0.91) and droplet‐transmitted infections (RR 0.26, 95% CI 0.16‐0.42) were significantly lower in the continuous N95 arm. Laboratory‐confirmed influenza was also lowest in the continuous N95 arm (RR 0.34, 95% CI 0.10‐1.11), but the difference was not statistically significant. Rates of laboratory‐confirmed bacterial colonisation (RR 0.54, 95% CI 0.33‐0.87) and droplet‐transmitted infections (RR 0.43, 95% CI 0.25‐0.72) were also lower in the targeted N95 arm, but not in medical mask arm. CONCLUSION: The results suggest that the classification of infections into droplet versus airborne transmission is an oversimplification. Most guidelines recommend masks for infections spread by droplets. N95 respirators, as “airborne precautions,” provide superior protection for droplet‐transmitted infections. To ensure the occupational health and safety of healthcare worker, the superiority of respirators in preventing respiratory infections should be reflected in infection control guidelines.",2017 Nov 30,"['MacIntyre, Chandini Raina', 'Chughtai, Abrar Ahmad', 'Rahman, Bayzidur', 'Peng, Yang', 'Zhang, Yi', 'Seale, Holly', 'Wang, Xiaoli', 'Wang, Quanyi']",Influenza Other Respir Viruses,,,True
5fa7de71e210e3f7884579d7da079c77fa0d5d6d,PMC,Public health implications of complex emergencies and natural disasters,http://dx.doi.org/10.1186/s13031-017-0135-8,PMC5706345,29209410,CC BY,"BACKGROUND: During the last decade, conflict or natural disasters have displaced unprecedented numbers of persons. This leads to conditions prone to outbreaks that imperil the health of displaced persons and threaten global health security. Past literature has minimally examined the association of communicable disease outbreaks with complex emergencies (CEs) and natural disasters (NDs). METHODS: To examine this association, we identified CEs and NDs using publicly available datasets from the Center for Research on the Epidemiology of Disasters and United Nations Flash and Consolidated Appeals archive for 2005–2014. We identified outbreaks from World Health Organization archives. We compared findings to identify overlap of outbreaks, including their types (whether or not of a vaccine-preventable disease), and emergency event types (CE, ND, or Both) by country and year using descriptive statistics and measure of association. RESULTS: There were 167 CEs, 912 NDs, 118 events linked to ‘Both’ types of emergencies, and 384 outbreaks. Of CEs, 43% were associated with an outbreak; 24% NDs were associated with an outbreak; and 36% of ‘Both’ types of emergencies were associated with an outbreak. Africa was disproportionately affected, where 67% of total CEs, 67% of ‘Both’ events (CE and ND), and 46% of all outbreaks occurred for the study period. The odds ratio of a vaccine-preventable outbreak occurring in a CE versus an ND was 4.14 (95% confidence limits 1.9, 9.4). CONCLUSIONS: CEs had greater odds of being associated with outbreaks compared with NDs. Moreover, CEs had high odds of a vaccine-preventable disease causing that outbreak. Focusing on better vaccine coverage could reduce CE-associated morbidity and mortality by preventing outbreaks from spreading.",2017 Nov 29,"['Culver, Amanda', 'Rochat, Roger', 'Cookson, Susan T.']",Confl Health,,,True
c417b7235950a6e64054e00d24f75e2e5c748349,PMC,Identification of a novel linear B-cell epitope in nonstructural protein 11 of porcine reproductive and respiratory syndrome virus that are conserved in both genotypes,http://dx.doi.org/10.1371/journal.pone.0188946,PMC5706702,29186182,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important pathogens, that hinder the development of global pork industry. Its nonstructural protein 11 (nsp11), with the nidoviral uridylate-specific endoribonuclease (NendoU) domain, is essential for PRRSV genome replication and it also contributes to host innate immunity suppression. However, the immunogenicity and immune structure of PRRSV nsp11 have not been well investigated yet. In this study, a monoclonal antibody (mAb), designated 3F9, that against nsp11 was generated. Subsequently, a series of partially overlapped fragments, covered the nsp11(40-223aa), were expressed to test the reactivity with mAb 3F9, and the (111)DCREY(115) was found to be the core unit of the B-cell epitope recognized by mAb 3F9. Further investigation indicated that both genotype 1 and genotype 2 PRRSV can be recognized by mAb 3F9, due to the (111)DCREY(115) is conserved in both genotype virus. Meanwhile, this epitope, localized at the surface of nsp11 in 3D structure, is confirmed to be able to induce humoral immune response in PRRSV infected pigs. These findings do not only provide an mAb tool to further investigate the function of nsp11, they also indicate the diagnostic potential for this epitope.",2017 Nov 29,"['Jiang, Nan', 'Jin, Huan', 'Li, Yi', 'Ge, Xinna', 'Han, Jun', 'Guo, Xin', 'Zhou, Lei', 'Yang, Hanchun']",PLoS One,,,True
471711362b8adb4bda402d22aebd264f63f8e1b7,PMC,Enrichment of Retroviral Sequences in Brain Tissue from Patients with Severe Demyelinating Diseases,,PMC5707126,29202119,CC BY,"BACKGROUND: Our group has used deep sequencing to identify viral RNA signatures in human brain specimens. We have previously used this method to detect HSV1, GBV-C, and measles virus sequence in brain tissue from deceased donors. Deep sequencing was performed on brain specimens from a cohort of patients who died with progressive forms of MS, revealing evidence of increased expression of some human endogenous retrovirus (HERV) domains. OBJECTIVES: Identify RNA sequences and new antigens involved in the pathogenesis of MS METHODS: Deep sequencing was performed on RNA extracted from 12 progressive MS, 2 neuromyelitis optica (MS/NMO = demyelination group), 14 normal control, and 7 other neurologic disease (OND) control frozen brain specimens. The resulting single-ended 50 bp sequences (reads) were compared to a non redundant viral database representing (NRVDB) all 1.2 M viral records in GenBank. A retroviral gene catalog (RVGC) was prepared by identifying human genetic loci (GRCh37.p13) homologous to domains contained in the Gypsy 2.0 retro element database. Reads were aligned to the RVGC and human transcriptome with Bowtie2. The resulting viral hit rates (VHRs) were normalized by the number of high quality reads. The expression of human genes, including HERVs, was determined using Cufflinks. Comparisons between the groups were performed using the false discovery rate. RESULTS: Fifty to 131 million high quality reads per specimen were obtained. Comparison of the reads to the NRVDB suggested that the demyelination and OND specimens had higher VHRs against some retroviral sequences compared with the controls. This was confirmed by retroviral domain averaging. Gene expression analysis showed differential expression among some HERV sequences. Single read mapping revealed one envelope and one reverse transcriptase sequence record that were significantly enriched among the demyelination samples compared to the normal controls. Less restrictive (comprehensive) read mapping showed that 2 integrase, 2 core, 2 envelope, and 3 KRAB sequences that were overexpressed in the demyelination group. CONCLUSIONS: These data demonstrate that some endogenous retroviral sequences are significantly overexpressed in these demyelination brain tissue specimens, but the magnitude of this overexpression is small. This is consistent with the concept of HERV activation as a part of the innate immune response.",2017 Aug 16,"['Kriesel, JD', 'Bhetariya, PJ', 'Chan, BK', 'Wilson, T', 'Fischer, KF']",J Emerg Dis Virol,,,True
322e9f87ee07bd71dd82ebf7e431c34580feef25,PMC,Oral Delivery of Probiotics Expressing Dendritic Cell-Targeting Peptide Fused with Porcine Epidemic Diarrhea Virus COE Antigen: A Promising Vaccine Strategy against PEDV,http://dx.doi.org/10.3390/v9110312,PMC5707519,29068402,CC BY,"Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, is the causative agent of porcine epidemic diarrhea (PED) that damages intestinal epithelial cells and results in severe diarrhea and dehydration in neonatal suckling pigs with up to 100% mortality. The oral vaccine route is reported as a promising approach for inducing protective immunity against PEDV invasion. Furthermore, dendritic cells (DCs), professional antigen-presenting cells, link humoral and cellular immune responses for homeostasis of the intestinal immune environment. In this study, in order to explore an efficient oral vaccine against PEDV infection, a mucosal DC-targeting oral vaccine was developed using Lactobacillus casei to deliver the DC-targeting peptide (DCpep) fused with the PEDV core neutralizing epitope (COE) antigen. This probiotic vaccine could efficiently elicit secretory immunoglobulin A (SIgA)-based mucosal and immunoglobulin G (IgG)-based humoral immune responses via oral vaccination in vivo. Significant differences (p < 0.05) in the immune response levels were observed between probiotics expressing the COE-DCpep fusion protein and COE antigen alone, suggesting better immune efficiency of the probiotics vaccine expressing the DC-targeting peptide fused with PEDV COE antigen. This mucosal DC-targeting oral vaccine delivery effectively enhances vaccine antigen delivery efficiency, providing a useful strategy to induce efficient immune responses against PEDV infection.",2017 Oct 25,"['Wang, Xiaona', 'Wang, Li', 'Huang, Xuewei', 'Ma, Sunting', 'Yu, Meiling', 'Shi, Wen', 'Qiao, Xinyuan', 'Tang, Lijie', 'Xu, Yigang', 'Li, Yijing']",Viruses,,,True
125b3f6dd69d07e5dac7fa45b6567008bd1244ae,PMC,Hazard Characterization of Modified Vaccinia Virus Ankara Vector: What Are the Knowledge Gaps?,http://dx.doi.org/10.3390/v9110318,PMC5707525,29109380,CC BY,"Modified vaccinia virus Ankara (MVA) is the vector of choice for human and veterinary applications due to its strong safety profile and immunogenicity in vivo. The use of MVA and MVA-vectored vaccines against human and animal diseases must comply with regulatory requirements as they pertain to environmental risk assessment, particularly the characterization of potential adverse effects to humans, animals and the environment. MVA and recombinant MVA are widely believed to pose low or negligible risk to ecosystem health. However, key aspects of MVA biology require further research in order to provide data needed to evaluate the potential risks that may occur due to the use of MVA and MVA-vectored vaccines. The purpose of this paper is to identify knowledge gaps in the biology of MVA and recombinant MVA that are of relevance to its hazard characterization and discuss ongoing and future experiments aimed at providing data necessary to fill in the knowledge gaps. In addition, we presented arguments for the inclusion of uncertainty analysis and experimental investigation of verifiable worst-case scenarios in the environmental risk assessment of MVA and recombinant MVA. These will contribute to improved risk assessment of MVA and recombinant MVA vaccines.",2017 Oct 29,"['Okeke, Malachy I.', 'Okoli, Arinze S.', 'Diaz, Diana', 'Offor, Collins', 'Oludotun, Taiwo G.', 'Tryland, Morten', 'Bøhn, Thomas', 'Moens, Ugo']",Viruses,,,True
f6fdeab5faa3141b4d0ba262210e6662a7aa261a,PMC,Hijacking of the Ubiquitin/Proteasome Pathway by the HIV Auxiliary Proteins,http://dx.doi.org/10.3390/v9110322,PMC5707529,29088112,CC BY,"The ubiquitin-proteasome system (UPS) ensures regulation of the protein pool in the cell by ubiquitination of proteins followed by their degradation by the proteasome. It plays a central role in the cell under normal physiological conditions as well as during viral infections. On the one hand, the UPS can be used by the cell to degrade viral proteins, thereby restricting the viral infection. On the other hand, it can also be subverted by the virus to its own advantage, notably to induce degradation of cellular restriction factors. This makes the UPS a central player in viral restriction and counter-restriction. In this respect, the human immunodeficiency viruses (HIV-1 and 2) represent excellent examples. Indeed, many steps of the HIV life cycle are restricted by cellular proteins, some of which are themselves components of the UPS. However, HIV itself hijacks the UPS to mediate defense against several cellular restriction factors. For example, the HIV auxiliary proteins Vif, Vpx and Vpu counteract specific restriction factors by the recruitment of cellular UPS components. In this review, we describe the interplay between HIV and the UPS to illustrate its role in the restriction of viral infections and its hijacking by viral proteins for counter-restriction.",2017 Oct 31,"['Seissler, Tanja', 'Marquet, Roland', 'Paillart, Jean-Christophe']",Viruses,,,True
9b5a336dab77072af21829b37a7b8318ae1dec6d,PMC,The 17th Rocky Mountain Virology Association Meeting,http://dx.doi.org/10.3390/v9110333,PMC5707540,29117106,CC BY,"Since 2000, scientists and students from the greater Rocky Mountain region, along with invited speakers, both national and international, have gathered at the Mountain Campus of Colorado State University to discuss their area of study, present recent findings, establish or strengthen collaborations, and mentor the next generation of virologists and prionologists through formal presentations and informal discussions concerning science, grantsmanship and network development. This year, approximately 100 people attended the 17th annual Rocky Mountain Virology Association meeting, that began with a keynote presentation, and featured 29 oral and 35 poster presentations covering RNA and DNA viruses, prions, virus-host interactions and guides to successful mentorship. Since the keynote address focused on the structure and function of Zika and related flaviviruses, a special session was held to discuss RNA control. The secluded meeting at the foot of the Colorado Rocky Mountains gave ample time for in-depth discussions amid the peak of fall colors in the aspen groves while the random bear provided excitement. On behalf of the Rocky Mountain Virology Association, this report summarizes the >50 reports.",2017 Nov 8,"['Rovnak, Joel', 'Perera, Rushika', 'Hopken, Matthew W.', 'Read, Jenna', 'Waller, Derrick M.', 'Cohrs, Randall J.']",Viruses,,,True
3cff423d90d10aed4310a7d726a6a873d37b2693,PMC,In vivo protection against ZIKV infection and pathogenesis through passive antibody transfer and active immunisation with a prMEnv DNA vaccine,http://dx.doi.org/10.1038/npjvaccines.2016.21,PMC5707885,29263859,CC BY,"Significant concerns have been raised owing to the rapid global spread of infection and disease caused by the mosquito-borne Zika virus (ZIKV). Recent studies suggest that ZIKV can also be transmitted sexually, further increasing the exposure risk for this virus. Associated with this spread is a dramatic increase in cases of microcephaly and additional congenital abnormalities in infants of ZIKV-infected mothers, as well as a rise in the occurrence of Guillain Barre’ syndrome in infected adults. Importantly, there are no licensed therapies or vaccines against ZIKV infection. In this study, we generate and evaluate the in vivo efficacy of a novel, synthetic, DNA vaccine targeting the pre-membrane+envelope proteins (prME) of ZIKV. Following initial in vitro development and evaluation studies of the plasmid construct, mice and non-human primates were immunised with this prME DNA-based immunogen through electroporation-mediated enhanced DNA delivery. Vaccinated animals were found to generate antigen-specific cellular and humoral immunity and neutralisation activity. In mice lacking receptors for interferon (IFN)-α/β (designated IFNAR(−/−)) immunisation with this DNA vaccine induced, following in vivo viral challenge, 100% protection against infection-associated weight loss or death in addition to preventing viral pathology in brain tissue. In addition, passive transfer of non-human primate anti-ZIKV immune serum protected IFNAR(−/−) mice against subsequent viral challenge. This study in NHP and in a pathogenic mouse model supports the importance of immune responses targeting prME in ZIKV infection and suggests that additional research on this vaccine approach may have relevance for ZIKV control and disease prevention in humans.",2016 Nov 10,"['Muthumani, Karuppiah', 'Griffin, Bryan D', 'Agarwal, Sangya', 'Kudchodkar, Sagar B', 'Reuschel, Emma L', 'Choi, Hyeree', 'Kraynyak, Kimberly A', 'Duperret, Elizabeth K', 'Keaton, Amelia Anne', 'Chung, Christopher', 'Kim, Yinho K', 'Booth, Stephanie A', 'Racine, Trina', 'Yan, Jian', 'Morrow, Matthew P', 'Jiang, Jingjing', 'Lee, Brian', 'Ramos, Stephanie', 'Broderick, Kate E', 'Reed, Charles C', 'Khan, Amir S', 'Humeau, Laurent', 'Ugen, Kenneth E', 'Park, Young K', 'Maslow, Joel N', 'Sardesai, Niranjan Y', 'Joseph Kim, J', 'Kobinger, Gary P', 'Weiner, David B']",NPJ Vaccines,,,True
fe13f9eaf3edd3aaa5e8cb92a882eec76caa3c9e,PMC,Vaccinology in the twenty-first century,http://dx.doi.org/10.1038/npjvaccines.2016.9,PMC5707890,29263852,CC BY,,2016 Jul 28,"Barrett, Alan D T",NPJ Vaccines,,,True
1a2c3991a18171055b98f12c29a2c1f5d5fef1bd,PMC,Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus,http://dx.doi.org/10.1371/journal.ppat.1006698,PMC5708621,29190287,CC BY,"A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.",2017 Nov 30,"['Hu, Ben', 'Zeng, Lei-Ping', 'Yang, Xing-Lou', 'Ge, Xing-Yi', 'Zhang, Wei', 'Li, Bei', 'Xie, Jia-Zheng', 'Shen, Xu-Rui', 'Zhang, Yun-Zhi', 'Wang, Ning', 'Luo, Dong-Sheng', 'Zheng, Xiao-Shuang', 'Wang, Mei-Niang', 'Daszak, Peter', 'Wang, Lin-Fa', 'Cui, Jie', 'Shi, Zheng-Li']",PLoS Pathog,,,True
b92029ab36511c3072b0a3cba99c6dbca29097cf,PMC,Autophagy pathway induced by a plant virus facilitates viral spread and transmission by its insect vector,http://dx.doi.org/10.1371/journal.ppat.1006727,PMC5708841,29125860,CC BY,"Many viral pathogens are persistently transmitted by insect vectors and cause agricultural or health problems. Generally, an insect vector can use autophagy as an intrinsic antiviral defense mechanism against viral infection. Whether viruses can evolve to exploit autophagy to promote their transmission by insect vectors is still unknown. Here, we show that the autophagic process is triggered by the persistent replication of a plant reovirus, rice gall dwarf virus (RGDV) in cultured leafhopper vector cells and in intact insects, as demonstrated by the appearance of obvious virus-containing double-membrane autophagosomes, conversion of ATG8-I to ATG8-II and increased level of autophagic flux. Such virus-containing autophagosomes seem able to mediate nonlytic viral release from cultured cells or facilitate viral spread in the leafhopper intestine. Applying the autophagy inhibitor 3-methyladenine or silencing the expression of Atg5 significantly decrease viral spread in vitro and in vivo, whereas applying the autophagy inducer rapamycin or silencing the expression of Torc1 facilitate such viral spread. Furthermore, we find that activation of autophagy facilitates efficient viral transmission, whereas inhibiting autophagy blocks viral transmission by its insect vector. Together, these results indicate a plant virus can induce the formation of autophagosomes for carrying virions, thus facilitating viral spread and transmission by its insect vector. We believe that such a role for virus-induced autophagy is common for vector-borne persistent viruses during their transmission by insect vectors.",2017 Nov 10,"['Chen, Yong', 'Chen, Qian', 'Li, Manman', 'Mao, Qianzhuo', 'Chen, Hongyan', 'Wu, Wei', 'Jia, Dongsheng', 'Wei, Taiyun']",PLoS Pathog,,,True
ffed4e8d373346115414598ac2c4165f10afebc9,PMC,Ribosomal stress and Tp53-mediated neuronal apoptosis in response to capsid protein of the Zika virus,http://dx.doi.org/10.1038/s41598-017-16952-8,PMC5709411,29192272,CC BY,"We report here that in rat and human neuroprogenitor cells as well as rat embryonic cortical neurons Zika virus (ZIKV) infection leads to ribosomal stress that is characterized by structural disruption of the nucleolus. The anti-nucleolar effects were most pronounced in postmitotic neurons. Moreover, in the latter system, nucleolar presence of ZIKV capsid protein (ZIKV-C) was associated with ribosomal stress and apoptosis. Deletion of 22 C-terminal residues of ZIKV-C prevented nucleolar localization, ribosomal stress and apoptosis. Consistent with a casual relationship between ZIKV-C-induced ribosomal stress and apoptosis, ZIKV-C-overexpressing neurons were protected by loss-of-function manipulations targeting the ribosomal stress effector Tp53 or knockdown of the ribosomal stress mediator RPL11. Finally, capsid protein of Dengue virus, but not West Nile virus, induced ribosomal stress and apoptosis. Thus, anti-nucleolar and pro-apoptotic effects of protein C are flavivirus-species specific. In the case of ZIKV, capsid protein-mediated ribosomal stress may contribute to neuronal death, neurodevelopmental disruption and microcephaly.",2017 Nov 30,"['Slomnicki, Lukasz P.', 'Chung, Dong-Hoon', 'Parker, Austin', 'Hermann, Taylor', 'Boyd, Nolan L.', 'Hetman, Michal']",Sci Rep,,,False
d9c9f9f03cb93fd7ddd3f409d8948f0ecf30445e,PMC,Ribosomal stress and Tp53-mediated neuronal apoptosis in response to capsid protein of the Zika virus,http://dx.doi.org/10.1038/s41598-017-16952-8,PMC5709411,29192272,CC BY,"We report here that in rat and human neuroprogenitor cells as well as rat embryonic cortical neurons Zika virus (ZIKV) infection leads to ribosomal stress that is characterized by structural disruption of the nucleolus. The anti-nucleolar effects were most pronounced in postmitotic neurons. Moreover, in the latter system, nucleolar presence of ZIKV capsid protein (ZIKV-C) was associated with ribosomal stress and apoptosis. Deletion of 22 C-terminal residues of ZIKV-C prevented nucleolar localization, ribosomal stress and apoptosis. Consistent with a casual relationship between ZIKV-C-induced ribosomal stress and apoptosis, ZIKV-C-overexpressing neurons were protected by loss-of-function manipulations targeting the ribosomal stress effector Tp53 or knockdown of the ribosomal stress mediator RPL11. Finally, capsid protein of Dengue virus, but not West Nile virus, induced ribosomal stress and apoptosis. Thus, anti-nucleolar and pro-apoptotic effects of protein C are flavivirus-species specific. In the case of ZIKV, capsid protein-mediated ribosomal stress may contribute to neuronal death, neurodevelopmental disruption and microcephaly.",2017 Nov 30,"['Slomnicki, Lukasz P.', 'Chung, Dong-Hoon', 'Parker, Austin', 'Hermann, Taylor', 'Boyd, Nolan L.', 'Hetman, Michal']",Sci Rep,,,True
cb44482e84ab91364682dfbcdb7ee5c9dd394f74,PMC,Characterization of the African Swine Fever Virus Decapping Enzyme during Infection,http://dx.doi.org/10.1128/JVI.00990-17,PMC5709586,29021398,CC BY,"African swine fever virus (ASFV) infection is characterized by a progressive decrease in cellular protein synthesis with a concomitant increase in viral protein synthesis, though the mechanism by which the virus achieves this is still unknown. Decrease of cellular mRNA is observed during ASFV infection, suggesting that inhibition of cellular proteins is due to an active mRNA degradation process. ASFV carries a gene (Ba71V D250R/Malawi g5R) that encodes a decapping protein (ASFV-DP) that has a Nudix hydrolase motif and decapping activity in vitro. Here, we show that ASFV-DP was expressed from early times and accumulated throughout the infection with a subcellular localization typical of the endoplasmic reticulum, colocalizing with the cap structure and interacting with the ribosomal protein L23a. ASFV-DP was capable of interaction with poly(A) RNA in cultured cells, primarily mediated by the N-terminal region of the protein. ASFV-DP also interacted with viral and cellular RNAs in the context of infection, and its overexpression in infected cells resulted in decreased levels of both types of transcripts. This study points to ASFV-DP as a viral decapping enzyme involved in both the degradation of cellular mRNA and the regulation of viral transcripts. IMPORTANCE Virulent ASFV strains cause a highly infectious and lethal disease in domestic pigs for which there is no vaccine. Since 2007, an outbreak in the Caucasus region has spread to Russia, jeopardizing the European pig population and making it essential to deepen knowledge about the virus. Here, we demonstrate that ASFV-DP is a novel RNA-binding protein implicated in the regulation of mRNA metabolism during infection, making it a good target for vaccine development.",2017 Nov 30,"['Quintas, Ana', 'Pérez-Núñez, Daniel', 'Sánchez, Elena G.', 'Nogal, Maria L.', 'Hentze, Matthias W.', 'Castelló, Alfredo', 'Revilla, Yolanda']",J Virol,,,True
eda0dbe156afeb8239f3dc2f50a74cdcba1b61d9,PMC,Characterization of the African Swine Fever Virus Decapping Enzyme during Infection,http://dx.doi.org/10.1128/JVI.00990-17,PMC5709586,29021398,CC BY,"African swine fever virus (ASFV) infection is characterized by a progressive decrease in cellular protein synthesis with a concomitant increase in viral protein synthesis, though the mechanism by which the virus achieves this is still unknown. Decrease of cellular mRNA is observed during ASFV infection, suggesting that inhibition of cellular proteins is due to an active mRNA degradation process. ASFV carries a gene (Ba71V D250R/Malawi g5R) that encodes a decapping protein (ASFV-DP) that has a Nudix hydrolase motif and decapping activity in vitro. Here, we show that ASFV-DP was expressed from early times and accumulated throughout the infection with a subcellular localization typical of the endoplasmic reticulum, colocalizing with the cap structure and interacting with the ribosomal protein L23a. ASFV-DP was capable of interaction with poly(A) RNA in cultured cells, primarily mediated by the N-terminal region of the protein. ASFV-DP also interacted with viral and cellular RNAs in the context of infection, and its overexpression in infected cells resulted in decreased levels of both types of transcripts. This study points to ASFV-DP as a viral decapping enzyme involved in both the degradation of cellular mRNA and the regulation of viral transcripts. IMPORTANCE Virulent ASFV strains cause a highly infectious and lethal disease in domestic pigs for which there is no vaccine. Since 2007, an outbreak in the Caucasus region has spread to Russia, jeopardizing the European pig population and making it essential to deepen knowledge about the virus. Here, we demonstrate that ASFV-DP is a novel RNA-binding protein implicated in the regulation of mRNA metabolism during infection, making it a good target for vaccine development.",2017 Nov 30,"['Quintas, Ana', 'Pérez-Núñez, Daniel', 'Sánchez, Elena G.', 'Nogal, Maria L.', 'Hentze, Matthias W.', 'Castelló, Alfredo', 'Revilla, Yolanda']",J Virol,,,False
5b1c9c575d37e7026b0c2c0fdfe309b7a06a528a,PMC,Evaluation of an accelerated hydrogen peroxide disinfectant to inactivate porcine epidemic diarrhea virus in swine feces on aluminum surfaces under freezing conditions,http://dx.doi.org/10.1186/s12917-017-1300-4,PMC5709983,29191202,CC BY,"BACKGROUND: Since its emergence in 2013, porcine epidemic diarrhea virus (PEDV) spread rapidly throughout the country due, in part, to contaminated livestock trailers. The objective of this study was to test the efficacy of an accelerated hydrogen peroxide (AHP) disinfectant for inactivating PEDV in swine feces on metal surfaces under freezing conditions. One 15.24 X 15.24 X 2.54 cm aluminum coupon, contaminated with swine feces, and randomly matched to one pig was the experimental unit. Eight treatment groups representing two AHP concentrations (1:16 and 1:32) in a 10% propylene glycol solution, two contact times in a -10 °C freezer (40 min and 60 min), and two levels of fecal contamination (5 mL and 10 mL) in addition to negative and positive control groups were evaluated. Forty 3-week-old pigs, intragastrically inoculated with the contents of the coupons after treatment, were used as a bioassay to determine the infectivity of PEDV after treatment. Infectivity was determined by detection of virus with a nucleocapsid (N) gene-based quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) on rectal swabs collected from the inoculated pigs on days three and seven post-inoculation. RESULTS: All post-treatment swabs from the negative control coupons were negative for PEDV via RT-qPCR. All post-treatment swabs collected from coupons in the AHP disinfectant treatment groups and the positive control group were positive for PEDV via RT-qPCR. For the bioassay, no rectal swabs from pigs in the negative control (0 of 4) or the AHP disinfectant treatment groups (0 of 32) were positive for PEDV. Rectal swabs from all pigs within the positive control group (4 of 4) were positive for PEDV by RT-qPCR. CONCLUSIONS: Under the conditions of this study, 1:16 and 1:32 dilutions of the AHP disinfectant successfully inactivated PEDV in swine feces on metal surfaces when applied at -10 °C with 40 or 60 min of contact time. This study also suggests that a positive RT-qPCR result for PEDV on an environmental sample should be expected when the AHP disinfectant is applied under freezing conditions, but does not necessarily indicate that an infectious dose of PEDV remains after disinfection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi: 10.1186/s12917-017-1300-4) contains supplementary material, which is available to authorized users.",2017 Dec 1,"['Baker, Kimberlee L.', 'Thomas, Paul R.', 'Karriker, Locke A.', 'Ramirez, Alejandro', 'Zhang, Jianqiang', 'Wang, Chong', 'Holtkamp, Derald J.']",BMC Vet Res,,,True
9d506eb7eb4546c382b5a83a2fa3b9e100ce2deb,PMC,Potential for broad-scale transmission of Ebola virus disease during the West Africa crisis: lessons for the Global Health security agenda,http://dx.doi.org/10.1186/s40249-017-0373-4,PMC5710062,29191243,CC BY,"BACKGROUND: The 2014–2016 Ebola crisis in West Africa had approximately eight times as many reported deaths as the sum of all previous Ebola outbreaks. The outbreak magnitude and occurrence of multiple Ebola cases in at least seven countries beyond Liberia, Sierra Leone, and Guinea, hinted at the possibility of broad-scale transmission of Ebola. MAIN TEXT: Using a modeling tool developed by the US Centers for Disease Control and Prevention during the Ebola outbreak, we estimated the number of Ebola cases that might have occurred had the disease spread beyond the three countries in West Africa to cities in other countries at high risk for disease transmission (based on late 2014 air travel patterns). We estimated Ebola cases in three scenarios: a delayed response, a Liberia-like response, and a fast response scenario. Based on our estimates of the number of Ebola cases that could have occurred had Ebola spread to other countries beyond the West African foci, we emphasize the need for improved levels of preparedness and response to public health threats, which is the goal of the Global Health Security Agenda. Our estimates suggest that Ebola could have potentially spread widely beyond the West Africa foci, had local and international health workers and organizations not committed to a major response effort. Our results underscore the importance of rapid detection and initiation of an effective, organized response, and the challenges faced by countries with limited public health systems. Actionable lessons for strengthening local public health systems in countries at high risk of disease transmission include increasing health personnel, bolstering primary and critical healthcare facilities, developing public health infrastructure (e.g. laboratory capacity), and improving disease surveillance. With stronger local public health systems infectious disease outbreaks would still occur, but their rapid escalation would be considerably less likely, minimizing the impact of public health threats such as Ebola. CONCLUSIONS: The Ebola outbreak could have potentially spread to other countries, where limited public health surveillance and response capabilities may have resulted in additional foci. Health security requires robust local health systems that can rapidly detect and effectively respond to an infectious disease outbreak. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-017-0373-4) contains supplementary material, which is available to authorized users.",2017 Dec 1,"['Undurraga, Eduardo A.', 'Carias, Cristina', 'Meltzer, Martin I.', 'Kahn, Emily B.']",Infect Dis Poverty,,,False
873d2ca5817ad916b491680ffc9e3260a8469e60,PMC,Potential for broad-scale transmission of Ebola virus disease during the West Africa crisis: lessons for the Global Health security agenda,http://dx.doi.org/10.1186/s40249-017-0373-4,PMC5710062,29191243,CC BY,"BACKGROUND: The 2014–2016 Ebola crisis in West Africa had approximately eight times as many reported deaths as the sum of all previous Ebola outbreaks. The outbreak magnitude and occurrence of multiple Ebola cases in at least seven countries beyond Liberia, Sierra Leone, and Guinea, hinted at the possibility of broad-scale transmission of Ebola. MAIN TEXT: Using a modeling tool developed by the US Centers for Disease Control and Prevention during the Ebola outbreak, we estimated the number of Ebola cases that might have occurred had the disease spread beyond the three countries in West Africa to cities in other countries at high risk for disease transmission (based on late 2014 air travel patterns). We estimated Ebola cases in three scenarios: a delayed response, a Liberia-like response, and a fast response scenario. Based on our estimates of the number of Ebola cases that could have occurred had Ebola spread to other countries beyond the West African foci, we emphasize the need for improved levels of preparedness and response to public health threats, which is the goal of the Global Health Security Agenda. Our estimates suggest that Ebola could have potentially spread widely beyond the West Africa foci, had local and international health workers and organizations not committed to a major response effort. Our results underscore the importance of rapid detection and initiation of an effective, organized response, and the challenges faced by countries with limited public health systems. Actionable lessons for strengthening local public health systems in countries at high risk of disease transmission include increasing health personnel, bolstering primary and critical healthcare facilities, developing public health infrastructure (e.g. laboratory capacity), and improving disease surveillance. With stronger local public health systems infectious disease outbreaks would still occur, but their rapid escalation would be considerably less likely, minimizing the impact of public health threats such as Ebola. CONCLUSIONS: The Ebola outbreak could have potentially spread to other countries, where limited public health surveillance and response capabilities may have resulted in additional foci. Health security requires robust local health systems that can rapidly detect and effectively respond to an infectious disease outbreak. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-017-0373-4) contains supplementary material, which is available to authorized users.",2017 Dec 1,"['Undurraga, Eduardo A.', 'Carias, Cristina', 'Meltzer, Martin I.', 'Kahn, Emily B.']",Infect Dis Poverty,,,True
76c35b758071bd154c5aa19cbacb5a044b1b6eb2,PMC,Potential for broad-scale transmission of Ebola virus disease during the West Africa crisis: lessons for the Global Health security agenda,http://dx.doi.org/10.1186/s40249-017-0373-4,PMC5710062,29191243,CC BY,"BACKGROUND: The 2014–2016 Ebola crisis in West Africa had approximately eight times as many reported deaths as the sum of all previous Ebola outbreaks. The outbreak magnitude and occurrence of multiple Ebola cases in at least seven countries beyond Liberia, Sierra Leone, and Guinea, hinted at the possibility of broad-scale transmission of Ebola. MAIN TEXT: Using a modeling tool developed by the US Centers for Disease Control and Prevention during the Ebola outbreak, we estimated the number of Ebola cases that might have occurred had the disease spread beyond the three countries in West Africa to cities in other countries at high risk for disease transmission (based on late 2014 air travel patterns). We estimated Ebola cases in three scenarios: a delayed response, a Liberia-like response, and a fast response scenario. Based on our estimates of the number of Ebola cases that could have occurred had Ebola spread to other countries beyond the West African foci, we emphasize the need for improved levels of preparedness and response to public health threats, which is the goal of the Global Health Security Agenda. Our estimates suggest that Ebola could have potentially spread widely beyond the West Africa foci, had local and international health workers and organizations not committed to a major response effort. Our results underscore the importance of rapid detection and initiation of an effective, organized response, and the challenges faced by countries with limited public health systems. Actionable lessons for strengthening local public health systems in countries at high risk of disease transmission include increasing health personnel, bolstering primary and critical healthcare facilities, developing public health infrastructure (e.g. laboratory capacity), and improving disease surveillance. With stronger local public health systems infectious disease outbreaks would still occur, but their rapid escalation would be considerably less likely, minimizing the impact of public health threats such as Ebola. CONCLUSIONS: The Ebola outbreak could have potentially spread to other countries, where limited public health surveillance and response capabilities may have resulted in additional foci. Health security requires robust local health systems that can rapidly detect and effectively respond to an infectious disease outbreak. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-017-0373-4) contains supplementary material, which is available to authorized users.",2017 Dec 1,"['Undurraga, Eduardo A.', 'Carias, Cristina', 'Meltzer, Martin I.', 'Kahn, Emily B.']",Infect Dis Poverty,,,True
f5fb59693963a0b96d112341f8f2a9f2b1d7a34c,PMC,Inhibition of Miro1 disturbs mitophagy and pancreatic β-cell function interfering insulin release via IRS-Akt-Foxo1 in diabetes,http://dx.doi.org/10.18632/oncotarget.20963,PMC5710878,29207597,CC BY,"Mitochondrial function is essential to meet metabolic demand of pancreatic beta cells respond to high nutrient stress. Mitophagy is an essential component to normal pancreatic β-cell function and has been associated with β-cell failure in Type 2 diabetes (T2D). Our previous studies have indicated that mitochondrial Rho (Miro) GTPase-mediated mitochondrial dysfunction under high nutrient stress leads to NOD-like receptor 3 (NLRP3)-dependent proinflammatory responses and subsequent insulin resistance. However, the in vivo mechanism by which Miro1 underlies mitophagy has not been identified. Here we show firstly that the expression of Miro is reduced in human T2D and mouse db/db islets and in INS-1 cell line exposed to high glucose and palmitate. β-cell specific ablation of Miro1 (Miro1f/f: Rip-cre mice, or (IKO) under high nutrient stress promotes the development of hyperglycemia. β-cells from IKO mice display an inhibition of mitophagy under oxidative stress and induces mitochondrial dysfunction. Dysfunctional mitophagy in IKO mice is represented by damaged islet beta cell mitochondrial and secretory capacity, unbalanced downstream MKK-JNK signalling without affecting the levels of MEK, ERK or p38 activation and subsequently, impaired insulin secretion signaling via inhibition IRS-AKT-Foxo1 pathway, leading to worsening glucose tolerance in these mice. Thus, these data suggest that Miro1 may be responsible for mitophagy deficiency and β-cell dysfunction in T2D and that strategies target Miro1 in vivo may provide a therapeutic target to enhance β-cell mitochondrial quality and insulin secretion to ameliorate complications associated with T2D.",2017 Sep 16,"['Chen, Lingling', 'Liu, Chunyan', 'Gao, Jianfeng', 'Xie, Zhiwen', 'Chan, Lawrence W.C.', 'Keating, Damien J.', 'Yang, Yibin', 'Sun, Jiazhong', 'Zhou, Fuling', 'Wei, Yongchang', 'Men, Xiuli', 'Yang, Sijun']",Oncotarget,,,True
a4b400b990198cfde2e1de4d789bf7793e91296c,PMC,Inhibition of Miro1 disturbs mitophagy and pancreatic β-cell function interfering insulin release via IRS-Akt-Foxo1 in diabetes,http://dx.doi.org/10.18632/oncotarget.20963,PMC5710878,29207597,CC BY,"Mitochondrial function is essential to meet metabolic demand of pancreatic beta cells respond to high nutrient stress. Mitophagy is an essential component to normal pancreatic β-cell function and has been associated with β-cell failure in Type 2 diabetes (T2D). Our previous studies have indicated that mitochondrial Rho (Miro) GTPase-mediated mitochondrial dysfunction under high nutrient stress leads to NOD-like receptor 3 (NLRP3)-dependent proinflammatory responses and subsequent insulin resistance. However, the in vivo mechanism by which Miro1 underlies mitophagy has not been identified. Here we show firstly that the expression of Miro is reduced in human T2D and mouse db/db islets and in INS-1 cell line exposed to high glucose and palmitate. β-cell specific ablation of Miro1 (Miro1f/f: Rip-cre mice, or (IKO) under high nutrient stress promotes the development of hyperglycemia. β-cells from IKO mice display an inhibition of mitophagy under oxidative stress and induces mitochondrial dysfunction. Dysfunctional mitophagy in IKO mice is represented by damaged islet beta cell mitochondrial and secretory capacity, unbalanced downstream MKK-JNK signalling without affecting the levels of MEK, ERK or p38 activation and subsequently, impaired insulin secretion signaling via inhibition IRS-AKT-Foxo1 pathway, leading to worsening glucose tolerance in these mice. Thus, these data suggest that Miro1 may be responsible for mitophagy deficiency and β-cell dysfunction in T2D and that strategies target Miro1 in vivo may provide a therapeutic target to enhance β-cell mitochondrial quality and insulin secretion to ameliorate complications associated with T2D.",2017 Sep 16,"['Chen, Lingling', 'Liu, Chunyan', 'Gao, Jianfeng', 'Xie, Zhiwen', 'Chan, Lawrence W.C.', 'Keating, Damien J.', 'Yang, Yibin', 'Sun, Jiazhong', 'Zhou, Fuling', 'Wei, Yongchang', 'Men, Xiuli', 'Yang, Sijun']",Oncotarget,,,False
2efb2e64e0fb3039c9fd9bd5abbebaf9d48ed216,PMC,Egr-1 regulates RTA transcription through a cooperative involvement of transcriptional regulators,http://dx.doi.org/10.18632/oncotarget.20648,PMC5710935,29207655,CC BY,"Kaposi’s sarcoma associated herpesvirus (KSHV) regulates the host cellular environment to establish life-long persistent infection by manipulating cellular signaling pathways, with approximately 1- 5% of cells undergoing lytic reactivation during the course of infection. Egr-1 (Early Growth Response Factor-1) is one such cellular transcription factor, which gets phosphorylated during the lytic phase of viral life cycle to perpetrate its function. This study demonstrates the mechanism of how Egr-1 mediates transcription of the immediate early gene, RTA (Replication and transcription activator), which is the lytic switch gene of KSHV. Egr-1 depleted KSHV infected cells exhibited reduced expression of RTA. Also, an increase in Egr-1 phosphorylation led to a higher virion production, which was suppressed in the presence of p38 and Raf inhibitors. Reporter assays showed that coexpression of Egr-1 and CBP (CREB-binding protein) enhances RTA promoter activity as compared to the expression of either Egr-1 or CBP alone. Binding of Egr-1 and CBP at RTA promoter was analyzed by chromatin immunoprecipitation assay (ChIP), which showed an enhanced accumulation during viral reactivation. Mutation in Egr-1 binding site of the RTA promoter eliminated Egr-1 response on promoter activation. Furthermore, de novo infection of THP-1 (monocytic) and HUVECs (endothelial) cells showed an upregulation of Egr-1 phosphorylation, whereas depletion of Egr-1 reduced the mRNA levels of RTA during primary infection. Together, these results demonstrate a cooperative role of Egr-1 and CBP in mediating RTA transcription, which significantly improves our understanding of the involvement of cellular factors controlling RTA transcription in KSHV pathogenesis.",2017 Sep 5,"['Sarkar, Roni', 'Verma, Subhash C.']",Oncotarget,,,True
989b3ab9e08bcef68a844c9a522771d41ddf7cad,PMC,Single Dose of Consensus Hemagglutinin-Based Virus-Like Particles Vaccine Protects Chickens against Divergent H5 Subtype Influenza Viruses,http://dx.doi.org/10.3389/fimmu.2017.01649,PMC5711813,29230222,CC BY,"The H5 subtype highly pathogenic avian influenza (HPAI) virus is one of the greatest threats to global poultry industry. To develop broadly protective H5 subunit vaccine, a recombinant consensus HA sequence (rHA) was constructed and expressed in virus-like particles (rHA VLPs) in the baculovirus-insect cell system. The efficacy of the rHA VLPs vaccine with or without immunopotentiator (CVCVA5) was assessed in chickens. Compared to the commercial Re6 or Re6-CVCVA5 vaccines, single dose immunization of chickens with rHA VLPs or rHA-CVCVA5 vaccines induced higher levels of serum hemagglutinin inhibition titers and neutralization titers, mucosal antibodies, IFN-γ and IL-4 cytokines in sera, and cytotoxic T lymphocyte responses. The rHA VLPs vaccine was superior to the commercial Re6 vaccine in conferring cross-protection against different clades of H5 subtype viruses. This study reports that H5 subtype consensus HA VLP single dose vaccination provides broad protection against HPAI virus in chickens.",2017 Nov 27,"['Wu, Peipei', 'Lu, Jihu', 'Zhang, Xuehua', 'Mei, Mei', 'Feng, Lei', 'Peng, Daxin', 'Hou, Jibo', 'Kang, Sang-Moo', 'Liu, Xiufan', 'Tang, Yinghua']",Front Immunol,,,True
8495f7c65f4a6cbce0e0d53c0900f10f6740826e,PMC,Viral Impact in Autoimmune Diseases: Expanding the “X Chromosome–Nucleolus Nexus” Hypothesis,http://dx.doi.org/10.3389/fimmu.2017.01657,PMC5712313,29234321,CC BY,"Viruses are suspected of significant roles in autoimmune diseases but the mechanisms are unclear. We get some insight by considering demands a virus places on host cells. Viruses not only require production of their own proteins, RNA and/or DNA, but also production of additional cellular machinery, such as ribosomes, to handle the increased demands. Since the nucleolus is a major site of RNA processing and ribonucleoprotein assembly, nucleoli are targeted by viruses, directly when viral RNA and proteins enter the nucleolus and indirectly when viruses induce increased expression of cellular polyamine genes. Polyamines are at high levels in nucleoli to assist in RNA folding. The size and activity of nucleoli increase directly with increases in polyamines. Nucleolar expansion due to abnormal increases in polyamines could disrupt nearby chromatin, such as the inactive X chromosome, leading to expression of previously sequestered DNA. Sudden expression of a large concentration of Alu elements from the disrupted inactive X can compete with RNA transcripts containing intronic Alu sequences that normally maintain nucleolar structural integrity. Such disruption of nucleolar activity can lead to misfolded RNAs, misassembled ribonucleoprotein complexes, and fragmentation of the nucleolus. Many autoantigens in lupus are, at least transiently, components of the nucleolus. Considering these effects of viruses, the “X chromosome–nucleolus nexus” hypothesis, which proposed disruption of the inactive X by the nucleolus during stress, is now expanded here to propose subsequent disruption of the nucleolus by previously sequestered Alu elements, which can fragment the nucleolus, leading to generation of autoantigens.",2017 Nov 28,"Brooks, Wesley H.",Front Immunol,,,True
6387603fb5f8eda220411438a86234c475aa728e,PMC,M(IL-4) Tissue Macrophages Support Efficient Interferon-Gamma Production in Antigen-Specific CD8(+) T Cells with Reduced Proliferative Capacity,http://dx.doi.org/10.3389/fimmu.2017.01629,PMC5714867,29250063,CC BY,"CD8(+) cytotoxic T cell (CTL) responses are necessary for the lysis of virally infected cells and control of infection. CTLs are activated when their TCRs bind a major histocompatibility complex (MHC)-I/peptide complex on the surface of antigen presenting cells such as macrophages (MΦ). It is now apparent that MΦ display remarkable plasticity in response to environmental signals to polarize into classically activated M(LPS + IFN-γ) or alternatively activated M(IL-4). However, little is known about how MΦ activation status influences their antigen presentation function to CD8(+) T cell in models of virus infection. Consequently, we tested how polarization of spleen-derived (Sp)-MΦ impacts direct presentation of viral antigens to influence effector and proliferative CD8(+) T-cell responses. We show that M(IL-4) Sp-MΦ retain MHC-I surface expression and the ability to stimulate IFN-γ production by CTL following peptide stimulation and lymphocytic choriomeningitis virus infection to levels similar to M0 and M(LPS + IFN-γ) MΦ. However, memory CD8(+) T cells cultured in the presence of M(IL-4) MΦ underwent significantly reduced proliferation and produced similar IFN-γ levels as coculturing with M0 or M(LPS + IFN-γ) cells. Thus, these results show a novel ability of polarized MΦ to regulate CD8(+) T-cell proliferation and effector functions during virus infection.",2017 Nov 30,"['Mulder, Rylend', 'Banete, Andra', 'Seaver, Kyle', 'Basta, Sameh']",Front Immunol,,,True
62cec1c466ff12e992da358837d6bbc59128f5d5,PMC,Antigen-specific oncolytic MV-based tumor vaccines through presentation of selected tumor-associated antigens on infected cells or virus-like particles,http://dx.doi.org/10.1038/s41598-017-16928-8,PMC5715114,29203786,CC BY,"Recombinant vaccine strain-derived measles virus (MV) is clinically tested both as vaccine platform to protect against other pathogens and as oncolytic virus for tumor treatment. To investigate the potential synergism in anti-tumoral efficacy of oncolytic and vaccine properties, we chose Ovalbumin and an ideal tumor antigen, claudin-6, for pre-clinical proof of concept. To enhance immunogenicity, both antigens were presented by retroviral virus-like particle produced in situ during MV-infection. All recombinant MV revealed normal growths, genetic stability, and proper expression and presentation of both antigens. Potent antigen-specific humoral and cellular immunity were found in immunized MV-susceptible IFNAR(−/−)-CD46Ge mice. These immune responses significantly inhibited metastasis formation or increased therapeutic efficacy compared to control MV in respective novel in vivo tumor models using syngeneic B16-hCD46/mCLDN6 murine melanoma cells. These data indicate the potential of MV to trigger selected tumor antigen-specific immune responses on top of direct tumor lysis for enhanced efficacy.",2017 Dec 4,"['Hutzler, Stefan', 'Erbar, Stephanie', 'Jabulowsky, Robert A.', 'Hanauer, Jan R. H.', 'Schnotz, Jürgen H.', 'Beissert, Tim', 'Bodmer, Bianca S.', 'Eberle, Regina', 'Boller, Klaus', 'Klamp, Thorsten', 'Sahin, Ugur', 'Mühlebach, Michael D.']",Sci Rep,,,False
3ba5a8bec872feebb62f6a1f384690ba1cd63a8b,PMC,Antigen-specific oncolytic MV-based tumor vaccines through presentation of selected tumor-associated antigens on infected cells or virus-like particles,http://dx.doi.org/10.1038/s41598-017-16928-8,PMC5715114,29203786,CC BY,"Recombinant vaccine strain-derived measles virus (MV) is clinically tested both as vaccine platform to protect against other pathogens and as oncolytic virus for tumor treatment. To investigate the potential synergism in anti-tumoral efficacy of oncolytic and vaccine properties, we chose Ovalbumin and an ideal tumor antigen, claudin-6, for pre-clinical proof of concept. To enhance immunogenicity, both antigens were presented by retroviral virus-like particle produced in situ during MV-infection. All recombinant MV revealed normal growths, genetic stability, and proper expression and presentation of both antigens. Potent antigen-specific humoral and cellular immunity were found in immunized MV-susceptible IFNAR(−/−)-CD46Ge mice. These immune responses significantly inhibited metastasis formation or increased therapeutic efficacy compared to control MV in respective novel in vivo tumor models using syngeneic B16-hCD46/mCLDN6 murine melanoma cells. These data indicate the potential of MV to trigger selected tumor antigen-specific immune responses on top of direct tumor lysis for enhanced efficacy.",2017 Dec 4,"['Hutzler, Stefan', 'Erbar, Stephanie', 'Jabulowsky, Robert A.', 'Hanauer, Jan R. H.', 'Schnotz, Jürgen H.', 'Beissert, Tim', 'Bodmer, Bianca S.', 'Eberle, Regina', 'Boller, Klaus', 'Klamp, Thorsten', 'Sahin, Ugur', 'Mühlebach, Michael D.']",Sci Rep,,,True
5e85184d2ba432306c3c21f22113aa590b09fe89,PMC,Neuronal CCL2 expression drives inflammatory monocyte infiltration into the brain during acute virus infection,http://dx.doi.org/10.1186/s12974-017-1015-2,PMC5715496,29202854,CC BY,"BACKGROUND: Viral encephalitis is a dangerous compromise between the need to robustly clear pathogen from the brain and the need to protect neurons from bystander injury. Theiler’s murine encephalomyelitis virus (TMEV) infection of C57Bl/6 mice is a model of viral encephalitis in which the compromise results in hippocampal damage and permanent neurological sequelae. We previously identified brain-infiltrating inflammatory monocytes as the primary driver of this hippocampal pathology, but the mechanisms involved in recruiting these cells to the brain were unclear. METHODS: Chemokine expression levels in the hippocampus were assessed by microarray, ELISA, RT-PCR, and immunofluorescence. Monocyte infiltration during acute TMEV infection was measured by flow cytometry. CCL2 levels were manipulated by immunodepletion and by specific removal from neurons in mice generated by crossing a line expressing the Cre recombinase behind the synapsin promoter to animals with floxed CCL2. RESULTS: Inoculation of the brain with TMEV induced hippocampal production of the proinflammatory chemokine CCL2 that peaked at 6 h postinfection, whereas inoculation with UV-inactivated TMEV did not elicit this response. Immunofluorescence revealed that hippocampal neurons expressed high levels of CCL2 at this timepoint. Genetic deletion of CCR2 and systemic immunodepletion of CCL2 abrogated or blunted the infiltration of inflammatory monocytes into the brain during acute infection. Specific genetic deletion of CCL2 from neurons reduced serum and hippocampal CCL2 levels and inhibited inflammatory monocyte infiltration into the brain. CONCLUSIONS: We conclude that intracranial inoculation with infectious TMEV rapidly induces the expression of CCL2 in neurons, and this cellular source is necessary for CCR2-dependent infiltration of inflammatory monocytes into the brain during the most acute stage of encephalitis. These findings highlight a unique role for neuronal production of chemokines in the initiation of leukocytic infiltration into the infected central nervous system.",2017 Dec 4,"['Howe, Charles L.', 'LaFrance-Corey, Reghann G.', 'Goddery, Emma N.', 'Johnson, Renee K.', 'Mirchia, Kanish']",J Neuroinflammation,,,True
80c9179236f8b034ec0763a86209141ea894b2ec,PMC,"Epidemiology of influenza in West Africa after the 2009 influenza A(H1N1) pandemic, 2010–2012",http://dx.doi.org/10.1186/s12879-017-2839-1,PMC5716025,29202715,CC BY,"BACKGROUND: Over the last decade, capacity for influenza surveillance and research in West Africa has strengthened. Data from these surveillance systems showed influenza A(H1N1)pdm09 circulated in West Africa later than in other regions of the continent. METHODS: We contacted 11 West African countries to collect information about their influenza surveillance systems (number of sites, type of surveillance, sampling strategy, populations sampled, case definitions used, number of specimens collected and number of specimens positive for influenza viruses) for the time period January 2010 through December 2012. RESULTS: Of the 11 countries contacted, 8 responded: Burkina Faso, Cote d’Ivoire, Mali, Mauritania, Niger, Nigeria, Sierra Leone and Togo. Countries used standard World Health Organization (WHO) case definitions for influenza-like illness (ILI) and severe acute respiratory illness (SARI) or slight variations thereof. There were 70 surveillance sites: 26 SARI and 44 ILI. Seven countries conducted SARI surveillance and collected 3114 specimens of which 209 (7%) were positive for influenza viruses. Among influenza-positive SARI patients, 132 (63%) were influenza A [68 influenza A(H1N1)pdm09, 64 influenza A(H3N2)] and 77 (37%) were influenza B. All eight countries conducted ILI surveillance and collected 20,375 specimens, of which 2278 (11%) were positive for influenza viruses. Among influenza-positive ILI patients, 1431 (63%) were influenza A [820 influenza A(H1N1)pdm09, 611 influenza A(H3N2)] and 847 (37%) were influenza B. A majority of SARI and ILI case-patients who tested positive for influenza (72% SARI and 59% ILI) were children aged 0–4 years, as were a majority of those enrolled in surveillance. The seasonality of influenza and the predominant influenza type or subtype varied by country and year. CONCLUSIONS: Influenza A(H1N1)pdm09 continued to circulate in West Africa along with influenza A(H3N2) and influenza B during 2010–2012. Although ILI surveillance systems produced a robust number of samples during the study period, more could be done to strengthen surveillance among hospitalized SARI case-patients. Surveillance systems captured young children but lacked data on adults and the elderly. More data on risk groups for severe influenza in West Africa are needed to help shape influenza prevention and clinical management policies and guidelines. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-017-2839-1) contains supplementary material, which is available to authorized users.",2017 Dec 4,"['Talla Nzussouo, Ndahwouh', 'Duque, Jazmin', 'Adedeji, Adebayo Abel', 'Coulibaly, Daouda', 'Sow, Samba', 'Tarnagda, Zekiba', 'Maman, Issaka', 'Lagare, Adamou', 'Makaya, Sonia', 'Elkory, Mohamed Brahim', 'Kadjo Adje, Herve', 'Shilo, Paul Alhassan', 'Tamboura, Boubou', 'Cisse, Assana', 'Badziklou, Kossi', 'Maïnassara, Halima Boubacar', 'Bara, Ahmed Ould', 'Keita, Adama Mamby', 'Williams, Thelma', 'Moen, Ann', 'Widdowson, Marc-Alain', 'McMorrow, Meredith']",BMC Infect Dis,,,True
cf08012c131b34b073bc10b82fcb6574b17d13b8,PMC,"Coinfection modulates inflammatory responses, clinical outcome and pathogen load of H1N1 swine influenza virus and Haemophilus parasuis infections in pigs",http://dx.doi.org/10.1186/s12917-017-1298-7,PMC5716233,29202835,CC BY,"BACKGROUND: Respiratory co-infections are important factor affecting the profitability of pigs production. Swine influenza virus (SIV) may predispose to secondary infection. Haemophilus parasuis (Hps) can be a primary pathogen or be associated with other pathogens such as SIV. To date, little is known about the effect of coinfection with SIV and Hps on the disease severity and inflammatory response and the role of Hps in the induction of pneumonia in the absence of other respiratory pathogens. In the study we investigated the influence of SIV and Hps coinfection on clinical course, inflammatory response, pathogens shedding and load at various time points following intranasal inoculation. The correlation between local concentration of cytokines and severity of disease as well as serum acute phase proteins (APP) concentration has been also studied. RESULTS: All co-infected pigs had fever, while in single inoculated pigs fever was observed only in part of animals. Necropsy revealed lesions in the lungs all SIV-inoculated and co-inoculated pigs, while in Hps-single inoculated animals only 1 out of 11 pigs revealed gross lung lesions. The SIV shedding was the highest in co-inoculated pigs. There were no differences between Hps-single inoculated and co-inoculated groups with regard to Hps shedding. The significant increase in Hps titre in the lung has been found only in co-inoculated group. All APP increased after co-infection. In single-inoculated animals various kinetics of APP response has been observed. The lung concentrations of cytokines were induced mostly in SIV + Hps pigs in the apical and middle lobe. These results correlated well with localization of gross lung lesions. CONCLUSIONS: The results revealed that SIV increased the severity of lung lesions and facilitated Hps (PIWetHps192/2015) replication in the porcine lung. Furthermore, Hps influenced the SIV nasal shedding. Enhanced Hps and SIV replication, together with stronger systemic and local inflammatory response contributed to a more severe clinical signs and stronger, earlier immune response in co-inoculated animals. We confirmed the previous evidence that single-Hps infection does not produce significant pneumonic lesions but it should be in mind that other strains of Hps may produce lesions different from that reported in the present study.",2017 Dec 4,"['Pomorska-Mól, Małgorzata', 'Dors, Arkadiusz', 'Kwit, Krzysztof', 'Czyżewska-Dors, Ewelina', 'Pejsak, Zygmunt']",BMC Vet Res,,,True
ef3260e6249c01ae263e65c11e59fe0279f70277,PMC,Linking disease epidemiology and livestock productivity: The case of bovine respiratory disease in France,http://dx.doi.org/10.1371/journal.pone.0189090,PMC5716546,29206855,CC BY,"Concerns are growing over the impact of livestock farming on environment and public health. The livestock industry is faced with the double constraint of limiting its use of natural resources and antimicrobials while ensuring its economic sustainability. In this context, reliable methods are needed to evaluate the effect of the prevention of endemic animal diseases on the productivity of livestock production systems. In this study, an epidemiological and productivity model was used to link changes in Bovine Respiratory Disease (BRD) incidence with the productivity of the beef and dairy cattle sectors in France. Cattle production parameters significantly affected by BRD were selected through literature review. Previous field study results and national cattle performance estimates were used to infer growth performances, mortality rates and carcass quality in the cattle affected and not affected by BRD. A steady-state deterministic herd production model was used to predict the productivity of the dairy and beef sector and their defined compartments (breeding-fattening, feedlot young bulls, and feedlot veal) in case of BRD incidence reduction by 20%, 50% or 100%. Results suggested that BRD should be controlled at a priority in beef breeding farms as eradication of BRD in beef calves would increase the whole beef sector’s productivity by 4.7–5.5% while eradication in other production stages would result in lower productivity gain in their respective sectors. However, the analysis performed at compartment level showed that, in both the beef and dairy sector, young bull and veal feedlot enterprises derive more economic benefits from BRD eradication for their own compartment (increase in productivity of 8.7–12.8% for beef young bulls) than the breeding farms (increase in productivity of 5.1–6% for beef calves), which may limit the investments in BRD control.",2017 Dec 5,"['Delabouglise, Alexis', 'James, Andrew', 'Valarcher, Jean-François', 'Hagglünd, Sara', 'Raboisson, Didier', 'Rushton, Jonathan']",PLoS One,,,True
8d6bcc2f1d98339588d638a0260826d7159d3049,PMC,Thymus transplantation for complete DiGeorge syndrome: European experience,http://dx.doi.org/10.1016/j.jaci.2017.03.020,PMC5716670,28400115,CC BY,"BACKGROUND: Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS). METHODS: Twelve patients with cDGS underwent transplantation with allogeneic cultured thymus. OBJECTIVE: We sought to confirm and extend the results previously obtained in a single center. RESULTS: Two patients died of pre-existing viral infections without having thymopoiesis, and 1 late death occurred from autoimmune thrombocytopenia. One infant had septic shock shortly after transplantation, resulting in graft loss and the need for a second transplant. Evidence of thymopoiesis developed from 5 to 6 months after transplantation in 10 patients. Median circulating naive CD4 counts were 44 × 10(6)/L (range, 11-440 × 10(6)/L) and 200 × 10(6)/L (range, 5-310 × 10(6)/L) at 12 and 24 months after transplantation and T-cell receptor excision circles were 2,238/10(6) T cells (range, 320-8,807/10(6) T cells) and 4,184/10(6) T cells (range, 1,582-24,596/10(6) T cells). Counts did not usually reach normal levels for age, but patients were able to clear pre-existing infections and those acquired later. At a median of 49 months (range, 22-80 months), 8 have ceased prophylactic antimicrobials, and 5 have ceased immunoglobulin replacement. Histologic confirmation of thymopoiesis was seen in 7 of 11 patients undergoing biopsy of transplanted tissue, including 5 showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator expression was also demonstrated. Autoimmune complications were seen in 7 of 12 patients. In 2 patients early transient autoimmune hemolysis settled after treatment and did not recur. The other 5 experienced ongoing autoimmune problems, including thyroiditis (3), hemolysis (1), thrombocytopenia (4), and neutropenia (1). CONCLUSIONS: This study confirms the previous reports that thymus transplantation can reconstitute T cells in patients with cDGS but with frequent autoimmune complications in survivors.",2017 Dec,"['Davies, E. Graham', 'Cheung, Melissa', 'Gilmour, Kimberly', 'Maimaris, Jesmeen', 'Curry, Joe', 'Furmanski, Anna', 'Sebire, Neil', 'Halliday, Neil', 'Mengrelis, Konstantinos', 'Adams, Stuart', 'Bernatoniene, Jolanta', 'Bremner, Ronald', 'Browning, Michael', 'Devlin, Blythe', 'Erichsen, Hans Christian', 'Gaspar, H. Bobby', 'Hutchison, Lizzie', 'Ip, Winnie', 'Ifversen, Marianne', 'Leahy, T. Ronan', 'McCarthy, Elizabeth', 'Moshous, Despina', 'Neuling, Kim', 'Pac, Malgorzata', 'Papadopol, Alina', 'Parsley, Kathryn L.', 'Poliani, Luigi', 'Ricciardelli, Ida', 'Sansom, David M.', 'Voor, Tiia', 'Worth, Austen', 'Crompton, Tessa', 'Markert, M. Louise', 'Thrasher, Adrian J.']",J Allergy Clin Immunol,,,False
e3b748c735f2ba33e17ce4d92cfac9293b1c4866,PMC,Association between nonspecific interstitial pneumonia and presence of CD20+ B lymphocytes within pulmonary lymphoid follicles,http://dx.doi.org/10.1038/s41598-017-17208-1,PMC5717047,29208971,CC BY,"Nonspecific interstitial pneumonia (NSIP) is characterised by interstitial infiltration of lymphocytes and varying amounts of interstitial fibrosis. B cells have been suggested to contribute to the pathogenesis of NSIP. However, the relationship between B-lymphocyte and the clinical outcomes of NSIP was unclear. In this study, 50 patients with histopathologically confirmed NSIP from Peking Union Medical College Hospital between April 2003 to December 2012 were retrospectively analyzed. Using immunohistochemical analyses, CD20+ B cells were counted in the lymphoid follicles, perivascular, interstitial, and peribronchiolar regions of lung tissure. The CD20+ lymphocytes were mainly present in the lymphoid follicles. The number of follicular CD20+ lymphocytes was higher in the fibrosing than cellular NSIP pattern [255.08 (132.92–449.71) vs. 121.33 (63.54–282.88)/0.1 mm(2), p = 0.017]. After 1 year of therapy, the follicular CD20+ lymphocytes were significantly higher in patients whose forced vital capacity (FVC) worsened as compared to those who improved (p = 0.014). Additionally, follicular CD20+ lymphocytes were negatively correlated with the post-treatment percentage change in FVC (rho = −0.397, p = 0.004). However, follicular CD20+ lymphocytes were not correlated with survival. These results suggested that pulmonary follicular CD20+ lymphocytes were correlated with the fibrosing pattern of NSIP and predicted less clinical improvement after treatment.",2017 Dec 5,"['Peng, Min', 'Wang, Wenze', 'Qin, Ling', 'Liu, Hongrui', 'Qin, Mingwei', 'Zheng, Wenjie', 'Shi, JuHong', 'Xu, Wenbing', 'Zhu, Yuanjue']",Sci Rep,,,True
5b97940d7cbe82e8c8b2482f6d6ab6fd45ecdbb1,PMC,Comparative genomic analysis of two emergent human adenovirus type 14 respiratory pathogen isolates in China reveals similar yet divergent genomes,http://dx.doi.org/10.1038/emi.2017.78,PMC5717082,29089589,CC BY,"Human adenovirus type 14 (HAdV-B14p) was originally identified as an acute respiratory disease (ARD) pathogen in The Netherlands in 1955. For approximately fifty years, few sporadic infections were observed. In 2005, HAdV-B14p1, a genomic variant, re-emerged and was associated with several large ARD outbreaks across the U.S. and, subsequently, in Canada, the U.K., Ireland, and China. This strain was associated with an unusually higher fatality rate than previously reported for both this prototype and other HAdV types in general. In China, HAdV-B14 was first observed in 2010, when two unrelated HAdV-B14-associated ARD cases were reported in Southern China (GZ01) and Northern China (BJ430), followed by three subsequent outbreaks. While comparative genomic analysis, including indel analysis, shows that the three China isolates, with whole genome data available, are similar to the de Wit prototype, all are divergent from the U.S. strain (303600; 2007). Although the genomes of strains GZ01 and BJ430 are nearly identical, as per their genome type characterization and percent identities, they are subtly divergent in their genome mutation patterns. These genomes indicate possibly two lineages of HAdV-B14 and independent introductions into China from abroad, or subsequent divergence from one; CHN2012 likely represents a separate sub-lineage. Observations of these simultaneously reported emergent strains in China add to the understanding of the circulation, epidemiology, and evolution of these HAdV pathogens, as well as provide a foundation for developing effective vaccines and public health strategies, including nationwide surveillance in anticipation of larger outbreaks with potentially higher fatality rates associated with HAdV-B14p1.",2017 Nov 1,"['Zhang, Qiwei', 'Jing, Shuping', 'Cheng, Zetao', 'Yu, Zhiwu', 'Dehghan, Shoaleh', 'Shamsaddini, Amirhossein', 'Yan, Yuqian', 'Li, Min', 'Seto, Donald']",Emerg Microbes Infect,,,True
19a804b052b806f48b58c353d70c4bda178ad87f,PMC,"Diversity of Middle East respiratory syndrome coronaviruses in 109 dromedary camels based on full-genome sequencing, Abu Dhabi, United Arab Emirates",http://dx.doi.org/10.1038/emi.2017.89,PMC5717090,29116217,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) was identified on the Arabian Peninsula in 2012 and is still causing cases and outbreaks in the Middle East. When MERS-CoV was first identified, the closest related virus was in bats; however, it has since been recognized that dromedary camels serve as a virus reservoir and potential source for human infections. A total of 376 camels were screened for MERS-Cov at a live animal market in the Eastern Region of the Emirate of Abu Dhabi, UAE. In all, 109 MERS-CoV-positive camels were detected in week 1, and a subset of positive camels were sampled again weeks 3 through 6. A total of 126 full and 3 nearly full genomes were obtained from 139 samples. Spike gene sequences were obtained from 5 of the 10 remaining samples. The camel MERS-CoV genomes from this study represent 3 known and 2 potentially new lineages within clade B. Within lineages, diversity of camel and human MERS-CoV sequences are intermixed. We identified sequences from market camels nearly identical to the previously reported 2015 German case who visited the market during his incubation period. We described 10 recombination events in the camel samples. The most frequent recombination breakpoint was the junctions between ORF1b and S. Evidence suggests MERS-CoV infection in humans results from continued introductions of distinct MERS-CoV lineages from camels. This hypothesis is supported by the camel MERS-CoV genomes sequenced in this study. Our study expands the known repertoire of camel MERS-CoVs circulating on the Arabian Peninsula.",2017 Nov 8,"['Yusof, Mohammed Farouk', 'Queen, Krista', 'Eltahir, Yassir Mohammed', 'Paden, Clinton R', 'Al Hammadi, Zulaikha Mohamed Abdel Hameed', 'Tao, Ying', 'Li, Yan', 'Khalafalla, Abdelmalik Ibrahim', 'Shi, Mang', 'Zhang, Jing', 'Mohamed, Muzammil Sayed Ahmed Elhaj', 'Abd Elaal Ahmed, Mahmud Hamed', 'Azeez, Ihsaan Abdulwahab', 'Bensalah, Oum Keltoum', 'Eldahab, Ziyada Swar', 'Al Hosani, Farida Ismail', 'Gerber, Susan I', 'Hall, Aron J', 'Tong, Suxiang', 'Al Muhairi, Salama Suhail']",Emerg Microbes Infect,,,True
fd70fe1475a302013f71a976dd9270cf5ecbe12e,PMC,HIV-1 Env DNA prime plus gp120 and gp70-V1V2 boosts induce high level of V1V2-specific IgG and ADCC responses and low level of Env-specific IgA response: implication for improving RV144 vaccine regimen,http://dx.doi.org/10.1038/emi.2017.90,PMC5717091,29184156,CC BY,,2017 Nov 29,"['Wang, Qian', 'Dai, Yanyan', 'Sun, Zhiwu', 'Su, Xiaojie', 'Yu, Yufeng', 'Hua, Chen', 'Xu, Wei', 'Jiang, Shibo', 'Lu, Lu']",Emerg Microbes Infect,,,True
dd673a8892d7431842f691147b9d4b1e6206b912,PMC,Utility of massive open online courses (MOOCs) concerning outbreaks of emerging and reemerging diseases,http://dx.doi.org/10.12688/f1000research.12639.2,PMC5717472,29259764,CC BY,"The emergence and re-emergence of infectious diseases such as Ebola, chikungunya, and Zika increase the necessity of knowledgeable and skilled health professionals. Massive open online courses (MOOCs) arise as opportunities that allow people around the world to participate in higher education courses. A search was conducted on specialized MOOC platforms to find courses related to outbreaks, using terms included in the list of the WHO disease outbreaks from January 1st to December 31 (st), 2016. We found seven courses about Ebola, two about Zika, three about the dynamics of epidemics and pandemics, and only one course about dengue, chikungunya, and malaria. Most of the courses were conducted in English. The courses on Ebola, Zika and chikungunya were released after their last outbreak. MOOCs could be used to learn about health issues of global relevance, and with the necessity of fast divulgation of knowledge and skills. Translating the courses into more languages could give these courses more traction, and allow participation of professionals in regions affected by these outbreaks.",2017 Dec 27,"['Bendezu-Quispe, Guido', 'Torres-Roman, Junior Smith', 'Salinas-Ochoa, Brenda', 'Hernández-Vásquez, Akram']",F1000Res,,,True
4439e815dce011452a7edf3a68f737f1dc40fae1,PMC,Anti-inflammatory activity of electron-deficient organometallics,http://dx.doi.org/10.1098/rsos.170786,PMC5717645,29291071,CC BY,"We report an evaluation of the cytotoxicity of a series of electron-deficient (16-electron) half-sandwich precious metal complexes of ruthenium, osmium and iridium ([Os/Ru(η(6)-p-cymene)(1,2-dicarba-closo-dodecarborane-1,2-dithiolato)] (1/2), [Ir(η(5)-pentamethylcyclopentadiene)(1,2-dicarba-closo-dodecarborane-1,2-dithiolato)] (3), [Os/Ru(η(6)-p-cymene)(benzene-1,2-dithiolato)] (4/5) and [Ir(η(5)-pentamethylcyclopentadiene)(benzene-1,2-dithiolato)] (6)) towards RAW 264.7 murine macrophages and MRC-5 fibroblast cells. Complexes 3 and 6 were found to be non-cytotoxic. The anti-inflammatory activity of 1–6 was evaluated in both cell lines after nitric oxide (NO) production and inflammation response induced by bacterial endotoxin lipopolysaccharide (LPS) as the stimulus. All metal complexes were shown to exhibit dose-dependent inhibitory effects on LPS-induced NO production on both cell lines. Remarkably, the two iridium complexes 3 and 6 trigger a full anti-inflammatory response against LPS-induced NO production, which opens up new avenues for the development of non-cytotoxic anti-inflammatory drug candidates with distinct structures and solution chemistry from that of organic drugs, and as such with potential novel mechanisms of action.",2017 Nov 29,"['Zhang, Jingwen', 'Pitto-Barry, Anaïs', 'Shang, Lijun', 'Barry, Nicolas P. E.']",R Soc Open Sci,,,True
47f676f779f052b93b78201643cc6f4d3213f979,PMC,Anti-inflammatory activity of electron-deficient organometallics,http://dx.doi.org/10.1098/rsos.170786,PMC5717645,29291071,CC BY,"We report an evaluation of the cytotoxicity of a series of electron-deficient (16-electron) half-sandwich precious metal complexes of ruthenium, osmium and iridium ([Os/Ru(η(6)-p-cymene)(1,2-dicarba-closo-dodecarborane-1,2-dithiolato)] (1/2), [Ir(η(5)-pentamethylcyclopentadiene)(1,2-dicarba-closo-dodecarborane-1,2-dithiolato)] (3), [Os/Ru(η(6)-p-cymene)(benzene-1,2-dithiolato)] (4/5) and [Ir(η(5)-pentamethylcyclopentadiene)(benzene-1,2-dithiolato)] (6)) towards RAW 264.7 murine macrophages and MRC-5 fibroblast cells. Complexes 3 and 6 were found to be non-cytotoxic. The anti-inflammatory activity of 1–6 was evaluated in both cell lines after nitric oxide (NO) production and inflammation response induced by bacterial endotoxin lipopolysaccharide (LPS) as the stimulus. All metal complexes were shown to exhibit dose-dependent inhibitory effects on LPS-induced NO production on both cell lines. Remarkably, the two iridium complexes 3 and 6 trigger a full anti-inflammatory response against LPS-induced NO production, which opens up new avenues for the development of non-cytotoxic anti-inflammatory drug candidates with distinct structures and solution chemistry from that of organic drugs, and as such with potential novel mechanisms of action.",2017 Nov 29,"['Zhang, Jingwen', 'Pitto-Barry, Anaïs', 'Shang, Lijun', 'Barry, Nicolas P. E.']",R Soc Open Sci,,,False
0b9d74a47a9b543089aaf5e91a0cfb6627e7de47,PMC,Anti-inflammatory activity of electron-deficient organometallics,http://dx.doi.org/10.1098/rsos.170786,PMC5717645,29291071,CC BY,"We report an evaluation of the cytotoxicity of a series of electron-deficient (16-electron) half-sandwich precious metal complexes of ruthenium, osmium and iridium ([Os/Ru(η(6)-p-cymene)(1,2-dicarba-closo-dodecarborane-1,2-dithiolato)] (1/2), [Ir(η(5)-pentamethylcyclopentadiene)(1,2-dicarba-closo-dodecarborane-1,2-dithiolato)] (3), [Os/Ru(η(6)-p-cymene)(benzene-1,2-dithiolato)] (4/5) and [Ir(η(5)-pentamethylcyclopentadiene)(benzene-1,2-dithiolato)] (6)) towards RAW 264.7 murine macrophages and MRC-5 fibroblast cells. Complexes 3 and 6 were found to be non-cytotoxic. The anti-inflammatory activity of 1–6 was evaluated in both cell lines after nitric oxide (NO) production and inflammation response induced by bacterial endotoxin lipopolysaccharide (LPS) as the stimulus. All metal complexes were shown to exhibit dose-dependent inhibitory effects on LPS-induced NO production on both cell lines. Remarkably, the two iridium complexes 3 and 6 trigger a full anti-inflammatory response against LPS-induced NO production, which opens up new avenues for the development of non-cytotoxic anti-inflammatory drug candidates with distinct structures and solution chemistry from that of organic drugs, and as such with potential novel mechanisms of action.",2017 Nov 29,"['Zhang, Jingwen', 'Pitto-Barry, Anaïs', 'Shang, Lijun', 'Barry, Nicolas P. E.']",R Soc Open Sci,,,False
7d262832606b297d4d1cd2af7a45578d10823418,PMC,Chimpanzee adenoviral vectors as vaccines for outbreak pathogens,http://dx.doi.org/10.1080/21645515.2017.1383575,PMC5718829,29083948,CC BY,"The 2014–15 Ebola outbreak in West Africa highlighted the potential for large disease outbreaks caused by emerging pathogens and has generated considerable focus on preparedness for future epidemics. Here we discuss drivers, strategies and practical considerations for developing vaccines against outbreak pathogens. Chimpanzee adenoviral (ChAd) vectors have been developed as vaccine candidates for multiple infectious diseases and prostate cancer. ChAd vectors are safe and induce antigen-specific cellular and humoral immunity in all age groups, as well as circumventing the problem of pre-existing immunity encountered with human Ad vectors. For these reasons, such viral vectors provide an attractive platform for stockpiling vaccines for emergency deployment in response to a threatened outbreak of an emerging pathogen. Work is already underway to develop vaccines against a number of other outbreak pathogens and we will also review progress on these approaches here, particularly for Lassa fever, Nipah and MERS.",2017 Oct 30,"['Ewer, Katie', 'Sebastian, Sarah', 'Spencer, Alexandra J.', 'Gilbert, Sarah', 'Hill, Adrian V. S.', 'Lambe, Teresa']",Hum Vaccin Immunother,,,True
33c50b9e506abf3c1db6bf58bd77b97155f9e903,PMC,Emerging and re-emerging infectious diseases in Iran,,PMC5719507,29225752,CC BY,"Despite development of preventive and controlling strategies regarding infectious diseases, they are still considered as one of the most significant leading causes of morbidity and mortality, worldwide. Changes in humans’ demographics and behaviors, microbial and ecological alterations, agricultural development, international travels and susceptibility to infectious diseases have resulted in increased reports of emerging infectious diseases (EIDs) and reemerging infectious diseases (RIDs) in various geographical areas. Because of the various types of geographic properties in Iran, substantial climatic variability, as well as unstable political situations and poor public health conditions in some of neighboring countries, EIDs and RIDs are serious public health problems; among them, zoonotic and drug resistant diseases are the most significant. Hence, this review provides an overview of the significant bacterial, viral and fungal EIDs and RIDs in Iran regarding their epidemiological aspects.",2017 Jun,"['Parhizgari, Najmeh', 'Gouya, Mohammad Mehdi', 'Mostafavi, Ehsan']",Iran J Microbiol,,,True
ec0a66b8b227c1a0ced88608d544e3b98120d557,PMC,"Bacteriological study of calf colisepticemia in Alage Dairy Farm, Southern Ethiopia",http://dx.doi.org/10.1186/s13104-017-3038-2,PMC5719531,29212529,CC BY,"OBJECTIVE: This study was designed to estimate the prevalence of E. coli which is the main cause of colisepticemia and the potential risk factors associated with the disease. A total of 74 calves less than 6 months age were selected for this study. For isolation and identification of E. coli, bacterial culture and biochemical tests were used. RESULT: Out of 74 calves selected for this study, 6 (8.11%) were positive for septicemic E. coli. Higher prevalence of 5 (8.93%) was recorded in Holstein Friesian breed than Boran breed 1 (5.56%). However, breed showed no significant difference on E. coli infections (P > 0.05). Higher prevalence of E. coli revealed below age of 30 days (17.39%) than calves aged between 30 and 90 days (8.33%) and above 90 days (0.00%). However, statistical association showed no difference (P > 0.05). Parity showed a significant difference in prevalence of E. coli (P < 0.05) in which infection increased with number of parity. Sex of the animal showed no association with infection of the calves (P > 0.05). Diarrheic calves showed higher prevalence (33.3%) than non-diarrheic calves (4.62%) with strong statistical association (P < 0.05). The present study showed a high prevalence of septicemic E. coli in the farm and intervention is strongly recommended.",2017 Dec 7,"['Tedla, Mebrahtu', 'Degefa, Kebede']",BMC Res Notes,,,True
f2e835d2cde5f42054dbd0c20d4060721135c518,PMC,"Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria",http://dx.doi.org/10.1186/s13104-017-3063-1,PMC5719735,29212531,CC BY,"OBJECTIVE: Recognizing increasing interest in community disease surveillance globally, the goal of this study was to investigate whether respiratory viruses circulating in the community may be represented through clinical (hospital) surveillance in Nigeria. RESULTS: Children were selected via convenience sampling from communities and a tertiary care center (n = 91) during spring 2017 in Ilorin, Nigeria. Nasal swabs were collected and tested using polymerase chain reaction. The majority (79.1%) of subjects were under 6 years old, of whom 46 were infected (63.9%). A total of 33 of the 91 subjects had one or more respiratory tract virus; there were 10 cases of triple infection and 5 of quadruple. Parainfluenza virus 4, respiratory syncytial virus B and enterovirus were the most common viruses in the clinical sample; present in 93.8% (15/16) of clinical subjects, and 6.7% (5/75) of community subjects (significant difference, p < 0.001). Coronavirus OC43 was the most common virus detected in community members (13.3%, 10/75). A different strain, Coronavirus OC 229 E/NL63 was detected among subjects from the clinic (2/16) and not detected in the community. This pilot study provides evidence that data from the community can potentially represent different information than that sourced clinically, suggesting the need for community surveillance to enhance public health efforts and scientific understanding of respiratory infections.",2017 Dec 7,"['Kolawole, Olatunji', 'Oguntoye, Michael', 'Dam, Tina', 'Chunara, Rumi']",BMC Res Notes,,,True
6302e80258b85ac4f27c6db06bcf9e245e981ba9,PMC,The impact of virus infections on pneumonia mortality is complex in adults: a prospective multicentre observational study,http://dx.doi.org/10.1186/s12879-017-2858-y,PMC5719746,29212450,CC BY,"BACKGROUND: Various viruses are known to be associated with pneumonia. However, the impact of viral infections on adult pneumonia mortality remains unclear. This study aimed to clarify the effect of virus infection on pneumonia mortality among adults stratified by virus type and patient comorbidities. METHODS: This multicentre prospective study enrolled pneumonia patients aged ≥15 years from September 2011 to August 2014. Sputum samples were tested by in-house multiplex polymerase chain reaction assays to identify 13 respiratory viruses. Viral infection status and its effect on in-hospital mortality were examined by age group and comorbidity status. RESULTS: A total of 2617 patients were enrolled in the study and 77.8% was aged ≥65 years. 574 (21.9%) did not have comorbidities, 790 (30.2%) had chronic respiratory disease, and 1253 (47.9%) had other comorbidities. Viruses were detected in 605 (23.1%) patients. Human rhinovirus (9.8%) was the most frequently identified virus, followed by influenza A (3.9%) and respiratory syncytial virus (3.9%). Respiratory syncytial virus was more frequently identified in patients with chronic respiratory disease (4.7%) than those with other comorbidities (4.2%) and without comorbidities (2.1%) (p = 0.037). The frequencies of other viruses were almost identical between the three groups. Virus detection overall was not associated with increased mortality (adjusted risk ratio (ARR) 0.76, 95% CI 0.53–1.09). However, influenza virus A and B were associated with three-fold higher mortality in patients with chronic respiratory disease but not with other comorbidities (ARR 3.38, 95% CI 1.54–7.42). Intriguingly, paramyxoviruses were associated with dramatically lower mortality in patients with other comorbidities (ARR 0.10, 95% CI 0.01–0.70) but not with chronic respiratory disease. These effects were not affected by age group. CONCLUSIONS: The impact of virus infections on pneumonia mortality varies by virus type and comorbidity status in adults. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-017-2858-y) contains supplementary material, which is available to authorized users.",2017 Dec 6,"['Katsurada, Naoko', 'Suzuki, Motoi', 'Aoshima, Masahiro', 'Yaegashi, Makito', 'Ishifuji, Tomoko', 'Asoh, Norichika', 'Hamashige, Naohisa', 'Abe, Masahiko', 'Ariyoshi, Koya', 'Morimoto, Konosuke', None]",BMC Infect Dis,,,True
8f9eda12b9470bd15725025244000aeb69b9ebb7,PMC,The glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells,http://dx.doi.org/10.1371/journal.pone.0189073,PMC5720808,29216247,CC BY,"Vesicular stomatitis virus (VSV) release from infected cells is inhibited by the interferon (IFN)-inducible antiviral host cell factor tetherin (BST-2, CD317). However, several viruses encode tetherin antagonists and it is at present unknown whether residual VSV spread in tetherin-positive cells is also promoted by a virus-encoded tetherin antagonist. Here, we show that the viral glycoprotein (VSV-G) antagonizes tetherin in transfected cells, although with reduced efficiency as compared to the HIV-1 Vpu protein. Tetherin antagonism did not involve alteration of tetherin expression and was partially dependent on a GXXXG motif in the transmembrane domain of VSV-G. However, mutation of the GXXXG motif did not modulate tetherin sensitivity of infectious VSV. These results identify VSV-G as a tetherin antagonist in transfected cells but fail to provide evidence for a contribution of tetherin antagonism to viral spread.",2017 Dec 7,"['Brinkmann, Constantin', 'Hoffmann, Markus', 'Lübke, Anastasia', 'Nehlmeier, Inga', 'Krämer-Kühl, Annika', 'Winkler, Michael', 'Pöhlmann, Stefan']",PLoS One,,,True
f2eaffec85de5ed3a8766b3e7185d819f71d8e5f,PMC,The glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells,http://dx.doi.org/10.1371/journal.pone.0189073,PMC5720808,29216247,CC BY,"Vesicular stomatitis virus (VSV) release from infected cells is inhibited by the interferon (IFN)-inducible antiviral host cell factor tetherin (BST-2, CD317). However, several viruses encode tetherin antagonists and it is at present unknown whether residual VSV spread in tetherin-positive cells is also promoted by a virus-encoded tetherin antagonist. Here, we show that the viral glycoprotein (VSV-G) antagonizes tetherin in transfected cells, although with reduced efficiency as compared to the HIV-1 Vpu protein. Tetherin antagonism did not involve alteration of tetherin expression and was partially dependent on a GXXXG motif in the transmembrane domain of VSV-G. However, mutation of the GXXXG motif did not modulate tetherin sensitivity of infectious VSV. These results identify VSV-G as a tetherin antagonist in transfected cells but fail to provide evidence for a contribution of tetherin antagonism to viral spread.",2017 Dec 7,"['Brinkmann, Constantin', 'Hoffmann, Markus', 'Lübke, Anastasia', 'Nehlmeier, Inga', 'Krämer-Kühl, Annika', 'Winkler, Michael', 'Pöhlmann, Stefan']",PLoS One,,,False
9403349de7bef7b3dfd86c83988cb24ade9a9ec9,PMC,Identifying spatio-temporal dynamics of Ebola in Sierra Leone using virus genomes,http://dx.doi.org/10.1098/rsif.2017.0583,PMC5721162,29187639,CC BY,"Containing the recent West African outbreak of Ebola virus (EBOV) required the deployment of substantial global resources. Despite recent progress in analysing and modelling EBOV epidemiological data, a complete characterization of the spatio-temporal spread of Ebola cases remains a challenge. In this work, we offer a novel perspective on the EBOV epidemic in Sierra Leone that uses individual virus genome sequences to inform population-level, spatial models. Calibrated to phylogenetic linkages of virus genomes, these spatial models provide unique insight into the disease mobility of EBOV in Sierra Leone without the need for human mobility data. Consistent with other investigations, our results show that the spread of EBOV during the beginning and middle portions of the epidemic strongly depended on the size of and distance between populations. Our phylodynamic analysis also revealed a change in model preference towards a spatial model with power-law characteristics in the latter portion of the epidemic, correlated with the timing of major intervention campaigns. More generally, we believe this framework, pairing molecular diagnostics with a dynamic model selection procedure, has the potential to be a powerful forecasting tool along with offering operationally relevant guidance for surveillance and sampling strategies during an epidemic.",2017 Nov 29,"['Gustafson, Kyle B.', 'Proctor, Joshua L.']",J R Soc Interface,,,True
81877a985b8974c5ff53940323d97a0f09185b26,PMC,Identifying spatio-temporal dynamics of Ebola in Sierra Leone using virus genomes,http://dx.doi.org/10.1098/rsif.2017.0583,PMC5721162,29187639,CC BY,"Containing the recent West African outbreak of Ebola virus (EBOV) required the deployment of substantial global resources. Despite recent progress in analysing and modelling EBOV epidemiological data, a complete characterization of the spatio-temporal spread of Ebola cases remains a challenge. In this work, we offer a novel perspective on the EBOV epidemic in Sierra Leone that uses individual virus genome sequences to inform population-level, spatial models. Calibrated to phylogenetic linkages of virus genomes, these spatial models provide unique insight into the disease mobility of EBOV in Sierra Leone without the need for human mobility data. Consistent with other investigations, our results show that the spread of EBOV during the beginning and middle portions of the epidemic strongly depended on the size of and distance between populations. Our phylodynamic analysis also revealed a change in model preference towards a spatial model with power-law characteristics in the latter portion of the epidemic, correlated with the timing of major intervention campaigns. More generally, we believe this framework, pairing molecular diagnostics with a dynamic model selection procedure, has the potential to be a powerful forecasting tool along with offering operationally relevant guidance for surveillance and sampling strategies during an epidemic.",2017 Nov 29,"['Gustafson, Kyle B.', 'Proctor, Joshua L.']",J R Soc Interface,,,False
e1e50e72368b173717a1b7f886c65c61ce5ade59,PMC,"Complete Genome Sequence of a Divergent Human Rhinovirus C Isolate from an Infant with Severe Community-Acquired Pneumonia in Colorado, USA",http://dx.doi.org/10.1128/genomeA.01245-17,PMC5722057,29192071,CC BY,"Here, we report the genome sequence of a divergent human rhinovirus C isolate identified from an infant with a severe community-acquired respiratory infection. RNA sequencing performed on an Illumina platform identified reads aligning to human rhinovirus species, which were de novo assembled to produce a coding-complete genome sequence.",2017 Nov 30,"['Langelier, Charles', 'White, Corin V.', 'Sontag, Marci K.', 'Mourani, Peter M.', 'DeRisi, Joseph L.']",Genome Announc,,,True
5a5a25d733b227ba661f3ba8f69af5886999f02c,PMC,Human cytomegalovirus and Herpes Simplex type I virus can engage RNA polymerase I for transcription of immediate early genes,http://dx.doi.org/10.18632/oncotarget.22106,PMC5722503,29228551,CC BY,"Human cytomegalovirus (HCMV) utilizes RNA polymerase II to transcribe viral genes and produce viral mRNAs. It can specifically target the nucleolus to facilitate viral transcription and translation. As RNA polymerase I (Pol I)-mediated transcription is active in the nucleolus, we investigated the role of Pol I, along with relative contributions of the human Pol II and Pol III, to early phases of viral transcription in HCMV infected cells, compared with Herpes Simplex Virus-1 (HSV-1) and Murine cytomegalovirus (MCMV). Inhibition of Pol I with siRNA or the Pol I inhibitors CX-5461 or Actinomycin D (5nM) resulted in significantly decreased IE and pp65 mRNA and protein levels in human fibroblasts at early times post infection. This initially delayed replication was compensated for later during the replication process, at which stage it didn’t significantly affect virus production. Pol I inhibition also reduced HSV-1 ICP0 and gB transcripts, suggesting that some herpesviruses engage Pol I for their early transcription. In contrast, inhibition of Pol I failed to affect MCMV transcription. Collectively, our results contribute to better understanding of the functional interplay between RNA Pol I-mediated nucleolar events and the Herpes viruses, particularly HCMV whose pathogenic impact ranges from congenital malformations and potentially deadly infections among immunosuppressed patients, up to HCMV’s emerging oncomodulatory role in human tumors.",2017 Oct 29,"['Kostopoulou, Ourania N.', 'Wilhelmi, Vanessa', 'Raiss, Sina', 'Ananthaseshan, Sharan', 'Lindström, Mikael S.', 'Bartek, Jiri', 'Söderberg-Naucler, Cecilia']",Oncotarget,,,True
96ff9bdec508a47524a0a60f0d6837de844a17ce,PMC,Human cytomegalovirus and Herpes Simplex type I virus can engage RNA polymerase I for transcription of immediate early genes,http://dx.doi.org/10.18632/oncotarget.22106,PMC5722503,29228551,CC BY,"Human cytomegalovirus (HCMV) utilizes RNA polymerase II to transcribe viral genes and produce viral mRNAs. It can specifically target the nucleolus to facilitate viral transcription and translation. As RNA polymerase I (Pol I)-mediated transcription is active in the nucleolus, we investigated the role of Pol I, along with relative contributions of the human Pol II and Pol III, to early phases of viral transcription in HCMV infected cells, compared with Herpes Simplex Virus-1 (HSV-1) and Murine cytomegalovirus (MCMV). Inhibition of Pol I with siRNA or the Pol I inhibitors CX-5461 or Actinomycin D (5nM) resulted in significantly decreased IE and pp65 mRNA and protein levels in human fibroblasts at early times post infection. This initially delayed replication was compensated for later during the replication process, at which stage it didn’t significantly affect virus production. Pol I inhibition also reduced HSV-1 ICP0 and gB transcripts, suggesting that some herpesviruses engage Pol I for their early transcription. In contrast, inhibition of Pol I failed to affect MCMV transcription. Collectively, our results contribute to better understanding of the functional interplay between RNA Pol I-mediated nucleolar events and the Herpes viruses, particularly HCMV whose pathogenic impact ranges from congenital malformations and potentially deadly infections among immunosuppressed patients, up to HCMV’s emerging oncomodulatory role in human tumors.",2017 Oct 29,"['Kostopoulou, Ourania N.', 'Wilhelmi, Vanessa', 'Raiss, Sina', 'Ananthaseshan, Sharan', 'Lindström, Mikael S.', 'Bartek, Jiri', 'Söderberg-Naucler, Cecilia']",Oncotarget,,,False
dd3c5f3af25e4c6fe5395625ed96d9244cd467b9,PMC,A multiplex liquid-chip assay based on Luminex xMAP technology for simultaneous detection of six common respiratory viruses,http://dx.doi.org/10.18632/oncotarget.18533,PMC5722533,29228581,CC BY,"We utilized one-step multiplex reverse transcription-PCR (RT-PCR) and Luminex xMAP technology to develop a respiratory multiplex liquid-chip assay (rMLA) for simultaneous detection of 6 common respiratory viruses, including influenza virus type A (FluA) and type B (FluB), para-influenza virus type 3 (PIV-3), respiratory syncytial virus (RSV), human metapneumovirus (MPV) and a threatening virus to China, Middle East Respiratory Syndrome coronavirus (MERS-CoV). Performance of rMLA was evaluated by comparing with real-time RT-PCR. Detection data from clinical specimens showed that the rMLA had diagnostic sensitivities of 97.10% for FluA, 94.59% for FluB, 98.68% for PIV-3, 94.87% for RSV and 95.92% for MPV (No Data for MERS-CoV due to the lack of positive specimens). Data of analytical sensitivities showed that the detection limits of the rMLA assay were 5–25 viral RNA copies per μl for FluA, FluB, PIV-3 and MERS-CoV, approximate to the real-time RT-PCR assay; while the values were 8 and 22copies/μl for MPV and RSV, lower than the real-time RT-PCR(78 and 114 copies/μl respectively). The results indicated that the rMLA is a sensitive, specific detection tool and comparable to real-time RT-PCR, especially suitable for high-throughput detection of respiratory specimens.",2017 Jun 17,"['Yan, Yong', 'Luo, Jian-Yong', 'Chen, Yin', 'Wang, Heng-Hui', 'Zhu, Guo-Ying', 'He, Pei-Yan', 'Guo, Jin-Lei', 'Lei, Yong-Liang', 'Chen, Zhong-Wen']",Oncotarget,,,True
722a5ed90b663c564f0ea7e7efd9eefc369f19be,PMC,Long term outcomes in survivors of epidemic Influenza A (H7N9) virus infection,http://dx.doi.org/10.1038/s41598-017-17497-6,PMC5722861,29222500,CC BY,"Patients who survive influenza A (H7N9) virus infection are at risk of physical and psychological complications of lung injury and multi-organ dysfunction. However, there were no prospectively individualized assessments of physiological, functional and quality-of-life measures after hospital discharge. The current study aims to assess the main determinants of functional disability of these patients during the follow-up. Fifty-six influenza A (H7N9) survivors were investigated during the 2-year after discharge from the hospital. Results show interstitial change and fibrosis on pulmonary imaging remained 6 months after hospital discharge. Both ventilation and diffusion dysfunction improved, but restrictive and obstructive patterns on ventilation function test persisted throughout the follow-up period. For patients with acute respiratory distress syndrome lung functions improved faster during the first six months. Role-physical and Role-emotional domains in the 36-Item Short-Form Health Survey were worse than those of a sex- and age-matched general population group. The quality of life of survivors with ARDS was lower than those with no ARDS. Our findings suggest that pulmonary function and imaging findings improved during the first 6 months especially for those with ARDS, however long-term lung disability and psychological impairment in H7N9 survivors persisted at 2 years after discharge from the hospital.",2017 Dec 8,"['Chen, Jiajia', 'Wu, Jie', 'Hao, Shaorui', 'Yang, Meifang', 'Lu, Xiaoqing', 'Chen, Xiaoxiao', 'Li, Lanjuan']",Sci Rep,,,True
03dce266594748330a10d2d11dbe611bf42aa42d,PMC,"Rhinovirus Biology, Antigenic Diversity, and Advancements in the Design of a Human Rhinovirus Vaccine",http://dx.doi.org/10.3389/fmicb.2017.02412,PMC5723287,29259600,CC BY,"Human rhinovirus (HRV) remains a leading cause of several human diseases including the common cold. Despite considerable research over the last 60 years, development of an effective vaccine to HRV has been viewed by many as unfeasible due, in part, to the antigenic diversity of circulating HRVs in nature. Over 150 antigenically distinct types of HRV are currently known which span three species: HRV A, HRV B, and HRV C. Early attempts to develop a rhinovirus vaccine have shown that inactivated HRV is capable of serving as a strong immunogen and inducing neutralizing antibodies. Yet, limitations to virus preparation and recovery, continued identification of antigenic variants of HRV, and logistical challenges pertaining to preparing a polyvalent preparation of the magnitude required for true efficacy against circulating rhinoviruses continue to prove a daunting challenge. In this review, we describe HRV biology, antigenic diversity, and past and present advances in HRV vaccine design.",2017 Dec 5,"['Stobart, Christopher C.', 'Nosek, Jenna M.', 'Moore, Martin L.']",Front Microbiol,,,True
e2fbe8d2a00bf0e7041a1b7c9e08c80ef87cb5cb,PMC,Preclinical Development and Production of Virus-Like Particles As Vaccine Candidates for Hepatitis C,http://dx.doi.org/10.3389/fmicb.2017.02413,PMC5723323,29259601,CC BY,"Hepatitis C Virus (HCV) infects 2% of the world’s population and is the leading cause of liver disease and liver transplantation. It poses a serious and growing worldwide public health problem that will only be partially addressed with the introduction of new antiviral therapies. However, these treatments will not prevent re-infection particularly in high risk populations. The introduction of a HCV vaccine has been predicted, using simulation models in a high risk population, to have a significant effect on reducing the incidence of HCV. A vaccine with 50 to 80% efficacy targeted to high-risk intravenous drug users could dramatically reduce HCV incidence in this population. Virus like particles (VLPs) are composed of viral structural proteins which self-assemble into non-infectious particles that lack genetic material and resemble native viruses. Thus, VLPs represent a safe and highly immunogenic vaccine delivery platform able to induce potent adaptive immune responses. Currently, many VLP-based vaccines have entered clinical trials, while licensed VLP vaccines for hepatitis B virus (HBV) and human papilloma virus (HPV) have been in use for many years. The HCV core, E1 and E2 proteins can self-assemble into immunogenic VLPs while inclusion of HCV antigens into heterogenous (chimeric) VLPs is also a promising approach. These VLPs are produced using different expression systems such as bacterial, yeast, mammalian, plant, or insect cells. Here, this paper will review HCV VLP-based vaccines and their immunogenicity in animal models as well as the different expression systems used in their production.",2017 Dec 5,"['Masavuli, Makutiro Ghislain', 'Wijesundara, Danushka K.', 'Torresi, Joseph', 'Gowans, Eric J.', 'Grubor-Bauk, Branka']",Front Microbiol,,,True
7fd0d03264447b79984a3a48e12470e08df672d0,PMC,Role of Incretin Axis in Inflammatory Bowel Disease,http://dx.doi.org/10.3389/fimmu.2017.01734,PMC5723660,29270177,CC BY,"The inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory conditions of the gastrointestinal tract and involve a complicated reciprocity of environmental, genetic, and immunologic factors. Despite substantial advances in the foundational understanding of the immunological pathogenesis of IBD, the detailed mechanism of the pathological progression in IBD remains unknown. In addition to Th1/Th2 cells, whose role in IBD has been previously well defined, recent evidence indicates that Th17 cells and Tregs also play a crucial role in the development of IBD. Diets which contain excess sugars, salt, and fat may also be important actors in the pathogenesis of IBD, which may be the cause of high IBD incidence in western developed and industrialized countries. Up until now, the reason for the variance in prevalence of IBD between developed and developing countries has been unknown. This is partly due to the increasing popularity of western diets in developing countries, which makes the data harder to interpret. The enterocrinins glucagon-like peptides (GLPs), including GLP-1 and GLP-2, exhibit notable benefits on lipid metabolism, atherosclerosis formation, plasma glucose levels, and maintenance of gastric mucosa integrity. In addition to the regulation of nutrient metabolism, the emerging role of GLPs and their degrading enzyme dipeptidyl peptidase-4 (DPP-4) in gastrointestinal diseases has gained increasing attention. Therefore, here we review the function of the DPP-4/GLP axis in IBD.",2017 Dec 6,"['Duan, Lihua', 'Rao, Xiaoquan', 'Braunstein, Zachary', 'Toomey, Amelia C.', 'Zhong, Jixin']",Front Immunol,,,True
c93e251c48b43dfc3e162039968b8ce59810c410,PMC,Interferon Lambda Genetics and Biology in Regulation of Viral Control,http://dx.doi.org/10.3389/fimmu.2017.01707,PMC5723907,29270173,CC BY,"Type III interferons, also known as interferon lambdas (IFNλs), are the most recent addition to the IFN family following their discovery in 2003. Initially, IFNλ was demonstrated to induce expression of interferon-stimulated genes and exert antiviral properties in a similar manner to type I IFNs. However, while IFNλ has been described to have largely overlapping expression and function with type I IFNs, it has become increasingly clear that type III IFNs also have distinct functions from type I IFNs. In contrast to type I IFNs, whose receptor is ubiquitously expressed, type III IFNs signal and function largely at barrier epithelial surfaces, such as the respiratory and gastrointestinal tracts, as well as the blood–brain barrier. In further support of unique functions for type III IFNs, single nucleotide polymorphisms in IFNL genes in humans are strongly associated with outcomes to viral infection. These biological linkages have also been more directly supported by studies in mice highlighting roles of IFNλ in promoting antiviral immune responses. In this review, we discuss the current understanding of type III IFNs, and how their functions are similar to, and different from, type I IFN in various immune cell subtypes and viral infections.",2017 Dec 6,"['Hemann, Emily A.', 'Gale, Michael', 'Savan, Ram']",Front Immunol,,,True
d26acf8967f074b793a42da11a49cf4bd1f87a66,PMC,Pulmonary exacerbations and clinical outcomes in a longitudinal cohort of infants and preschool children with cystic fibrosis,http://dx.doi.org/10.1186/s12890-017-0546-8,PMC5725640,29228933,CC BY,"BACKGROUND: Pulmonary exacerbations (PEx) in school aged children and adults with cystic fibrosis (CF) lead to increased morbidity and lung function decline. However, the effect of exacerbations in young children with CF is not fully understood. We sought to characterize the frequency and clinical impact of PEx in a pilot study of infants and pre-school aged children with CF. METHODS: Thirty young children with CF [median (range) 1.5 years (0.2–4.9)] were prospectively followed for 2 years. Exacerbation frequency (hospitalizations and outpatient antibiotic use) was determined. Chest radiographs were performed at enrollment and study completion and assigned a Brasfield score. Lung function at age 7 years was assessed in a subset of children. The association between PEx frequency, chest radiograph score, and lung function was determined using Spearman correlation coefficients and corresponding 95% confidence intervals. Correlations with an absolute magnitude of 0.3 or greater were considered clinically significant. RESULTS: Over 2 years, participants experienced a median of two PEx (range 0–13). Chest radiograph scores at enrollment and study completion were inversely associated with PEx frequency (R = −0.48 and R = −0.44, respectively). The association between frequency of PEx and lung function [forced expiratory volume in 1 s (FEV(1))] at age 7 years was small (R = 0.20). Higher forced vital capacity (FVC) at 7 years was associated with more frequent PEx during the study (R = 0.44). CONCLUSIONS: Children with worse chest radiograph scores had more frequent PEx over the subsequent 2 years, suggesting a group of patients at higher risk for PEx. Frequent PEx in infants and young children with CF were not associated with lower FEV(1) and FVC at 7 years, although spirometry in this age group may not be a sensitive marker of mild lung disease and disease progression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12890-017-0546-8) contains supplementary material, which is available to authorized users.",2017 Dec 11,"['Hoppe, Jordana E.', 'Wagner, Brandie D.', 'Sagel, Scott D.', 'Accurso, Frank J.', 'Zemanick, Edith T.']",BMC Pulm Med,,,False
67e7efbd1d4c301ca5e676c366dbaf31f3bf3949,PMC,Pulmonary exacerbations and clinical outcomes in a longitudinal cohort of infants and preschool children with cystic fibrosis,http://dx.doi.org/10.1186/s12890-017-0546-8,PMC5725640,29228933,CC BY,"BACKGROUND: Pulmonary exacerbations (PEx) in school aged children and adults with cystic fibrosis (CF) lead to increased morbidity and lung function decline. However, the effect of exacerbations in young children with CF is not fully understood. We sought to characterize the frequency and clinical impact of PEx in a pilot study of infants and pre-school aged children with CF. METHODS: Thirty young children with CF [median (range) 1.5 years (0.2–4.9)] were prospectively followed for 2 years. Exacerbation frequency (hospitalizations and outpatient antibiotic use) was determined. Chest radiographs were performed at enrollment and study completion and assigned a Brasfield score. Lung function at age 7 years was assessed in a subset of children. The association between PEx frequency, chest radiograph score, and lung function was determined using Spearman correlation coefficients and corresponding 95% confidence intervals. Correlations with an absolute magnitude of 0.3 or greater were considered clinically significant. RESULTS: Over 2 years, participants experienced a median of two PEx (range 0–13). Chest radiograph scores at enrollment and study completion were inversely associated with PEx frequency (R = −0.48 and R = −0.44, respectively). The association between frequency of PEx and lung function [forced expiratory volume in 1 s (FEV(1))] at age 7 years was small (R = 0.20). Higher forced vital capacity (FVC) at 7 years was associated with more frequent PEx during the study (R = 0.44). CONCLUSIONS: Children with worse chest radiograph scores had more frequent PEx over the subsequent 2 years, suggesting a group of patients at higher risk for PEx. Frequent PEx in infants and young children with CF were not associated with lower FEV(1) and FVC at 7 years, although spirometry in this age group may not be a sensitive marker of mild lung disease and disease progression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12890-017-0546-8) contains supplementary material, which is available to authorized users.",2017 Dec 11,"['Hoppe, Jordana E.', 'Wagner, Brandie D.', 'Sagel, Scott D.', 'Accurso, Frank J.', 'Zemanick, Edith T.']",BMC Pulm Med,,,True
9a63f7c66c750e9076dfb9d04319c1811cd49e00,PMC,Novel insights into bat influenza A viruses,http://dx.doi.org/10.1099/jgv.0.000927,PMC5725989,28906230,CC BY,"In 2012 and 2013, influenza virus genome sequences of two new influenza A virus (IAV) subtypes were discovered in bat specimens, but further characterization was largely impeded by the lack of infectious virus. With the identification of highly susceptible cell lines, reconstitution of infectious bat IAV by reverse genetics recently succeeded and allowed a first insight into the life cycle of these viruses. Although there is a certain degree of functional compatibility between bat and conventional influenza A virus proteins, there are striking differences, including receptor usage, polarity of infection and reassortment potential.",2017 Oct 14,"['Ciminski, Kevin', 'Thamamongood, Thiprampai', 'Zimmer, Gert', 'Schwemmle, Martin']",J Gen Virol,,,True
7081473cf95db2a82c1960a38625593cab0dc0f4,PMC,"Ensuring HIV Data Availability, Transparency and Integrity in the MENA Region: Comment on ""Improving the Quality and Quantity of HIV Data in the Middle East and North Africa: Key Challenges and Ways Forward""",http://dx.doi.org/10.15171/ijhpm.2017.53,PMC5726325,29172382,CC BY,"In this commentary, we elaborate on the main points that Karamouzian and colleagues have made about HIV data scarcity in Middle Eastern and North African (MENA) countries. Without accessible and reliable data, no epidemic can be managed effectively or efficiently. Clearly, increased investments are needed to bolster capabilities to capture and interpret HIV surveillance data. We believe that this enhanced capacity can be achieved, in part, by leveraging and repurposing existing data platforms, technologies and patient cohorts. An immediate modest investment that capitalizes on available infrastructure can generate data on the HIV burden and spread that can be persuasive for MENA policy-makers to intensify efforts to track and contain the growing HIV epidemic in this region. A focus on key populations will yield the most valuable data, including among men who have sex with men (MSM), transgender women and men, persons who inject drugs (PWIDs), female partners of high risk men and female sex workers.",2017 May 22,"['Modjarrad, Kayvon', 'Vermund, Sten H.']",Int J Health Policy Manag,,,True
8f68f74a604135502f3fbfe4f802713377bfa51b,PMC,"DUSP1 regulates apoptosis and cell migration, but not the JIP1-protected cytokine response, during Respiratory Syncytial Virus and Sendai Virus infection",http://dx.doi.org/10.1038/s41598-017-17689-0,PMC5727028,29234123,CC BY,"The host antiviral response involves the induction of interferons and proinflammatory cytokines, but also the activation of cell death pathways, including apoptosis, to limit viral replication and spreading. This host defense is strictly regulated to eliminate the infection while limiting tissue damage that is associated with virus pathogenesis. Post-translational modifications, most notably phosphorylation, are key regulators of the antiviral defense implying an important role of protein phosphatases. Here, we investigated the role of the dual-specificity phosphatase 1 (DUSP1) in the host defense against human respiratory syncytial virus (RSV), a pathogenic virus of the Pneumoviridae family, and Sendai virus (SeV), a model virus being developed as a vector for anti-RSV vaccine. We found that DUSP1 is upregulated before being subjected to proteasomal degradation. DUSP1 does not inhibit the antiviral response, but negatively regulates virus-induced JNK/p38 MAPK phosphorylation. Interaction with the JNK-interacting protein 1 scaffold protein prevents dephosphorylation of JNK by DUSP1, likely explaining that AP-1 activation and downstream cytokine production are protected from DUSP1 inhibition. Importantly, DUSP1 promotes SeV-induced apoptosis and suppresses cell migration in RSV-infected cells. Collectively, our data unveils a previously unrecognized selective role of DUSP1 in the regulation of tissue damage and repair during infections by RSV and SeV.",2017 Dec 12,"['Robitaille, Alexa C.', 'Caron, Elise', 'Zucchini, Nicolas', 'Mukawera, Espérance', 'Adam, Damien', 'Mariani, Mélissa K.', 'Gélinas, Anaïs', 'Fortin, Audray', 'Brochiero, Emmanuelle', 'Grandvaux, Nathalie']",Sci Rep,,,False
5deb9073195a49301f2eb72bc7d327ea2e9393e3,PMC,"DUSP1 regulates apoptosis and cell migration, but not the JIP1-protected cytokine response, during Respiratory Syncytial Virus and Sendai Virus infection",http://dx.doi.org/10.1038/s41598-017-17689-0,PMC5727028,29234123,CC BY,"The host antiviral response involves the induction of interferons and proinflammatory cytokines, but also the activation of cell death pathways, including apoptosis, to limit viral replication and spreading. This host defense is strictly regulated to eliminate the infection while limiting tissue damage that is associated with virus pathogenesis. Post-translational modifications, most notably phosphorylation, are key regulators of the antiviral defense implying an important role of protein phosphatases. Here, we investigated the role of the dual-specificity phosphatase 1 (DUSP1) in the host defense against human respiratory syncytial virus (RSV), a pathogenic virus of the Pneumoviridae family, and Sendai virus (SeV), a model virus being developed as a vector for anti-RSV vaccine. We found that DUSP1 is upregulated before being subjected to proteasomal degradation. DUSP1 does not inhibit the antiviral response, but negatively regulates virus-induced JNK/p38 MAPK phosphorylation. Interaction with the JNK-interacting protein 1 scaffold protein prevents dephosphorylation of JNK by DUSP1, likely explaining that AP-1 activation and downstream cytokine production are protected from DUSP1 inhibition. Importantly, DUSP1 promotes SeV-induced apoptosis and suppresses cell migration in RSV-infected cells. Collectively, our data unveils a previously unrecognized selective role of DUSP1 in the regulation of tissue damage and repair during infections by RSV and SeV.",2017 Dec 12,"['Robitaille, Alexa C.', 'Caron, Elise', 'Zucchini, Nicolas', 'Mukawera, Espérance', 'Adam, Damien', 'Mariani, Mélissa K.', 'Gélinas, Anaïs', 'Fortin, Audray', 'Brochiero, Emmanuelle', 'Grandvaux, Nathalie']",Sci Rep,,,True
8c17c17e58e174ba99b3964a2ddd1a0a4b9a35d4,PMC,Altered Gut Microbiota Profiles in Sows and Neonatal Piglets Associated with Porcine Epidemic Diarrhea Virus Infection,http://dx.doi.org/10.1038/s41598-017-17830-z,PMC5727058,29234140,CC BY,"Porcine epidemic diarrhea virus (PEDV) is a devastating cause of diarrhea in pigs worldwide. Most of studies have focused on molecular and pathogenic characterization of PEDV, whereas there were limited studies in understanding the role of gut microbiota (GM) in viral-associated diarrhea. Here, using the Illumina MiSeq platform, we examined and compared the impact of PEDV infection on the GM of sows and their piglets less than 10 days old. Our results showed that PEDV caused alternations in the structure and abundance of GM from levels of phylum to genus, and even species. For sows, a significant decrease of observed species was found in diarrheal sows than that in healthy sows (p < 0.05). The unweighted and weighted UniFrac distances also revealed considerable segregations of GM structure among healthy, asymptomatic, and diarrheal sows. For piglets, Bacteroidetes, the dominant bacteria in healthy piglets, were replaced by Firmicutes in asymptomatic and diarrheal piglets. The abundances of Fusobacteria and Proteobacteria were also remarkably increased in asymptomatic piglets and diarrheal piglets when compared to those of the healthy piglets. Our findings demonstrated that PEDV infection caused severe perturbations of GM, reduced probiotic bacteria, and enriched pathogenic bacteria.",2017 Dec 12,"['Song, Deping', 'Peng, Qi', 'Chen, Yanjun', 'Zhou, Xinrong', 'Zhang, Fanfan', 'Li, Anqi', 'Huang, Dongyan', 'Wu, Qiong', 'Ye, Yu', 'He, Houjun', 'Wang, Leyi', 'Tang, Yuxin']",Sci Rep,,,True
76585719cd2c0b067b878acf53964015a47bb917,PMC,Altered Gut Microbiota Profiles in Sows and Neonatal Piglets Associated with Porcine Epidemic Diarrhea Virus Infection,http://dx.doi.org/10.1038/s41598-017-17830-z,PMC5727058,29234140,CC BY,"Porcine epidemic diarrhea virus (PEDV) is a devastating cause of diarrhea in pigs worldwide. Most of studies have focused on molecular and pathogenic characterization of PEDV, whereas there were limited studies in understanding the role of gut microbiota (GM) in viral-associated diarrhea. Here, using the Illumina MiSeq platform, we examined and compared the impact of PEDV infection on the GM of sows and their piglets less than 10 days old. Our results showed that PEDV caused alternations in the structure and abundance of GM from levels of phylum to genus, and even species. For sows, a significant decrease of observed species was found in diarrheal sows than that in healthy sows (p < 0.05). The unweighted and weighted UniFrac distances also revealed considerable segregations of GM structure among healthy, asymptomatic, and diarrheal sows. For piglets, Bacteroidetes, the dominant bacteria in healthy piglets, were replaced by Firmicutes in asymptomatic and diarrheal piglets. The abundances of Fusobacteria and Proteobacteria were also remarkably increased in asymptomatic piglets and diarrheal piglets when compared to those of the healthy piglets. Our findings demonstrated that PEDV infection caused severe perturbations of GM, reduced probiotic bacteria, and enriched pathogenic bacteria.",2017 Dec 12,"['Song, Deping', 'Peng, Qi', 'Chen, Yanjun', 'Zhou, Xinrong', 'Zhang, Fanfan', 'Li, Anqi', 'Huang, Dongyan', 'Wu, Qiong', 'Ye, Yu', 'He, Houjun', 'Wang, Leyi', 'Tang, Yuxin']",Sci Rep,,,True
7a215215f74fbf094c929a521c28cacc1fef4dcd,PMC,Patterns of infectious complications in acute myeloid leukemia and myelodysplastic syndromes patients treated with 10‐day decitabine regimen,http://dx.doi.org/10.1002/cam4.1231,PMC5727246,29058375,CC BY,"Decitabine has been explored as a reduced‐intensity therapy for older or unfit patients with acute myeloid leukemia (AML). To better understand the risk of infections during decitabine treatment, we retrospectively examined the culture results from each infection‐related serious adverse event that occurred among 85 AML and myelodysplastic syndromes (MDS) patients treated in a prospective clinical study using 10‐day cycles of decitabine at Washington University School of Medicine. Culture results were available for 163 infection‐related complications that occurred in 70 patients: 90 (55.2%) events were culture‐negative, 32 (19.6%) were gram‐positive bacteria, 20 (12.3%) were gram‐negative bacteria, 12 (7.4%) were mixed, 6 (3.7%) were viral, 2 (1.2%) were fungal, and 1 (0.6%) was mycobacterial. Infection‐related mortality occurred in 3/24 (13%) of gram‐negative events, and 0/51 gram‐positive events. On average, nearly one third of patients experienced an infection‐related complication with each cycle, and the incidence did not decrease during later cycles. In summary, in patients receiving 10‐day decitabine, infectious complications are common and may occur during any cycle of therapy. Although febrile events are commonly culture‐negative, gram‐positive infections are the most frequent source of culture‐positive infections, but gram‐negative infections represent a significant risk of mortality in AML and MDS patients treated with decitabine.",2017 Oct 23,"['Ali, Alaa M.', 'Weisel, Daniel', 'Gao, Feng', 'Uy, Geoffrey L.', 'Cashen, Amanda F.', 'Jacoby, Meagan A.', 'Wartman, Lukas D.', 'Ghobadi, Armin', 'Pusic, Iskra', 'Romee, Rizwan', 'Fehniger, Todd A.', 'Stockerl‐Goldstein, Keith E.', 'Vij, Ravi', 'Oh, Stephen T.', 'Abboud, Camille N.', 'Schroeder, Mark A.', 'Westervelt, Peter', 'DiPersio, John F.', 'Welch, John S.']",Cancer Med,,,True
6aa72847e6c019bbc18254ec5cca30db62200120,PMC,Immune-Mediated Damage Completes the Parabola: Cryptococcus neoformans Pathogenesis Can Reflect the Outcome of a Weak or Strong Immune Response,http://dx.doi.org/10.1128/mBio.02063-17,PMC5727418,29233901,CC BY,"Cryptococcosis occurs most frequently in immunocompromised individuals. This has led to the prevailing view that this disease is the result of weak immune responses that cannot control the fungus. However, increasingly, clinical and experimental studies have revealed that the host immune response can contribute to cryptococcal pathogenesis, including the recent study of L. M. Neal et al. (mBio 8:e01415-17, 2017, https://doi.org/10.1128/mBio.01415-17) that reports that CD4(+) T cells mediate tissue damage in experimental murine cryptococcosis. This finding has fundamental implications for our understanding of the pathogenesis of cryptococcal disease; it helps explain why immunotherapy has been largely unsuccessful in treatment and provides insight into the paradoxical observation that HIV-associated cryptococcosis may have a better prognosis than cryptococcosis in those with no known immune impairment. The demonstration that host-mediated damage can drive cryptococcal disease provides proof of concept that the parabola put forth in the damage-response framework has the flexibility to depict complex and changing outcomes of host-microbe interaction.",2017 Dec 12,"['Pirofski, Liise-anne', 'Casadevall, Arturo']",mBio,,,True
637c82c1bb56fb9d7ff5a5a2b1c9645a80180065,PMC,One-plasmid double-expression His-tag system for rapid production and easy purification of MS2 phage-like particles,http://dx.doi.org/10.1038/s41598-017-17951-5,PMC5727534,29235545,CC BY,"MS2 phage-like particles (MS2 PLP) are artificially constructed pseudo-viral particles derived from bacteriophage MS2. They are able to carry a specific single stranded RNA (ssRNA) sequence of choice inside their capsid, thus protecting it against the effects of ubiquitous nucleases. Such particles are able to mimic ssRNA viruses and, thus, may serve as the process control for molecular detection and quantification of such agents in several kinds of matrices, vaccines and vaccine candidates, drug delivery systems, and systems for the display of immunologically active peptides or nanomachines. Currently, there are several different in vivo plasmid-driven packaging systems for production of MS2 PLP. In order to combine all the advantages of the available systems and to upgrade and simplify the production and purification of MS2 PLP, a one-plasmid double-expression His-tag system was designed. The described system utilizes a unique fusion insertional mutation enabling purification of particles using His-tag affinity. Using this new production system, highly pure MS2 PLP can be quickly produced and purified by a fast performance liquid chromatography (FPLC) approach. The system can be easily adapted to produce other MS2 PLP with different properties.",2017 Dec 13,"['Mikel, Pavel', 'Vasickova, Petra', 'Kralik, Petr']",Sci Rep,,,True
ab93177f9535fe5635e94d021785133011c87d93,PMC,"Investigation using whole genome sequencing of a prolonged restaurant outbreak of Salmonella Typhimurium linked to the building drainage system, England, February 2015 to March 2016",http://dx.doi.org/10.2807/1560-7917.ES.2017.22.49.17-00037,PMC5727591,29233257,CC BY,"Following notification of a Salmonella enterica serovar Typhimurium gastroenteritis outbreak, we identified 82 cases linked to a restaurant with symptom onset from 12 February 2015 to 8 March 2016. Seventy-two cases had an isolate matching the nationally unique whole genome sequencing profile (single nucleotide polymorphism (SNP) address: 1.1.1.124.395.395). Interviews established exposure to the restaurant and subsequent case–control analysis identified an association with eating carvery buffet food (adjusted odds ratios (AOR): 20.9; 95% confidence interval (CI): 2.2 – ∞). Environmental inspections, food/water testing, and a food trace-back investigation were inconclusive. Repeated cycles of cleaning were undertaken, including hydrogen peroxide fogging, however, transmission continued. After 7 months of investigation, environmental swabbing identified 106 isolates from kitchen surfaces and restaurant drains matching the outbreak profile. We found structural faults with the drainage system and hypothesised that a reservoir of bacteria in drain biofilm and underfloor flooded areas may have sustained this outbreak. Ineffective drain water-traps (U-bends) may have also contributed by allowing transmission of contaminated aerosols into the kitchen environment. These findings suggest that routine swabbing of sink drain points and inspection of drainage systems should be considered in future outbreak scenarios.",2017 Dec 7,"['Mair-Jenkins, John', 'Borges-Stewart, Roberta', 'Harbour, Caroline', 'Cox-Rogers, Judith', 'Dallman, Tim', 'Ashton, Philip', 'Johnston, Robert', 'Modha, Deborah', 'Monk, Philip', 'Puleston, Richard']",Euro Surveill,,,True
68050f9429a9f9fe023c51014f830e9d2572d2d9,PMC,Clinical analysis of 23 cases of steroid-associated osteonecrosis of the femoral head with normal initial magnetic resonance imaging presentation,http://dx.doi.org/10.1097/MD.0000000000008834,PMC5728861,29245246,CC BY,"To explore the clinical characteristics of steroid-associated osteonecrosis of the femoral head (ONFH) presenting initially normal magnetic resonance imaging (MRI) results. This retrospective study examined data from 23 cases that suffered from ONFH but presented a normal image at the first MRI examination after corticosteroid therapy from June 2005 to December 2013. Data on protopathy, age, sex, time of pain onset, MRI examination, and initial diagnosis were collected and analyzed. Average time from steroid therapy to first MRI examination was 45.7 ± 25.5 days (range, 10–94 days). Average time to final diagnosis was 199.9 ± 165.8 days (range, 32–762 days). Of the 23 cases, 21 cases complained of discomfort and were misdiagnosed because of a normal initial MRI scan. Twelve hips progressed to collapse and 1 hip received lumbar discectomy when got the final diagnosis. Cases with continuous pain (9/21) presented with pain at a later time than those with intermittent pain (12/21), although the continuous pain cases were diagnosed earlier. MRI performed 2 to 3 months after steroid therapy may present normal images. Another MRI examination is necessary to make a definite diagnosis.",2017 Dec 8,"['Zhao, Feng-Chao', 'Hu, Huai-Xia', 'Zheng, Xin', 'Cang, Ding-Wei', 'Liu, Xiaoyun', 'Zhang, Jian-Zhi', 'Guo, Kai-Jin']",Medicine (Baltimore),,,True
dabb3cd242342b19aadc8f9eadd2677a18deac13,PMC,Recombinant human ACE2: acing out angiotensin II in ARDS therapy,http://dx.doi.org/10.1186/s13054-017-1882-z,PMC5729230,29237475,CC BY,,2017 Dec 13,"['Zhang, Haibo', 'Baker, Andrew']",Crit Care,,,True
72761826ce01da1fe5599c79547746b44fe5ec49,PMC,Rapid detection of infectious bovine Rhinotracheitis virus using recombinase polymerase amplification assays,http://dx.doi.org/10.1186/s12917-017-1284-0,PMC5729238,29237466,CC BY,"BACKGROUND: Infectious bovine rhinotracheitis virus (IBRV) is a major pathogen in cattle and has led to significant economic losses to the dairy industry worldwide, and therefore a more optimal method for the rapid diagnosis of IBRV infection is highly needed. In this study, we described the development of a lateral flow dipstrip (LFD) of isothermal recombinase polymerase amplification (RPA) method for rapid detection of IBRV. METHODS: Distinct regions were selected as a candidate target for designing the LFD-RPA primers and probes. The analytical sensitivity of the RPA assay was determined using ten-fold serially diluted IBRV DNA. The specificity of the assay was assessed with other viral pathogens of cattle with similar clinic and other herpesviruses. The clinical performance was evaluated by testing 106 acute-phase high fever clinical specimens. RESULTS: RPA primers and probe were designed to target the specific conserved UL52 region fragment of IBRV. The detection could be completed at a constant temperature of 38 °C for 25 min, and the amplification products were easily visualized on a simple LFD. The detection limit of this assay was 5 copies per reaction of IBRV DNA and there was no cross-reactivity with other viruses causing bovine gastrointestinal and respiratory infections or other herpesviruses. The assay performance on acute-phase high fever clinical samples collected from cattle with no vaccine against IBRV, which were suspected to be infected with IBRV, was validated by detecting 24 fecal, 36 blood, 38 nasal swab and 8 tissue specimens, and compared with SYBR Green I based real-time PCR. The coincidence between IBRV LFD-RPA and real-time PCR was 100%. CONCLUSION: IBRV LFD-RPA was fast and much easier to serve as an alternative to the common measures used for IBRV diagnosis, as there is reduction in the use of instruments for identification of the infected animals. In addition, this assay may be the potential candidate to be used as point-of-care diagnostics in the field.",2017 Dec 13,"['Hou, Peili', 'Wang, Hongmei', 'Zhao, Guimin', 'He, Chengqiang', 'He, Hongbin']",BMC Vet Res,,,True
97f0a7e6ca8d48ac37eb4bf5c1aa47f9ab80ffd6,PMC,Performance of the Alere i RSV assay for point-of-care detection of respiratory syncytial virus in children,http://dx.doi.org/10.1186/s12879-017-2855-1,PMC5729395,29237419,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is the most important cause of severe acute respiratory tract infection in young children. Alere i RSV is a novel molecular rapid test which identifies respiratory syncytial virus in less than 13 min. METHODS: We evaluated the clinical performance of the Alere i RSV assay in a pediatric point-of-care setting during winter season 2016 / 2017. Test results from 518 nasopharyngeal swab samples were compared to a real-time reverse transcription PCR reference standard. RESULTS: The overall sensitivity and specificity of the Alere i RSV test assay was 93% (CI(95) 89% – 96%) and 96% (CI(95) 93% – 98%), respectively. Alere i RSV performed well in children of all age groups. An optimal sensitivity of 98% (CI(95) 94% - 100%) and specificity of 96% (CI(95) 90% - 99%) was obtained in children < 6 months. In children ≥ 2 years, sensitivity and specificity remained at 87% (CI(95) 73% – 96%) and 98% (CI(95) 92% – 100%), respectively. False negative Alere i RSV test results mostly occurred in samples with low viral load (mean CT value 31.1; CI(95) 29.6 – 32.6). The Alere i RSV assay is easy to use and can be operated after minimal initial training. Test results are available within 13 min, with most RSV positive samples being identified after approximately 5 min. CONCLUSION: The Alere i RSV assay has the potential to facilitate the detection of RSV in pediatric point-of-care settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-017-2855-1) contains supplementary material, which is available to authorized users.",2017 Dec 13,"['Schnee, Sarah Valerie', 'Pfeil, Johannes', 'Ihling, Clara Marlene', 'Tabatabai, Julia', 'Schnitzler, Paul']",BMC Infect Dis,,,True
dc502e4494d5ef1e5a2f54b5df88e7c391d9a763,PMC,"Virulence, pathology, and pathogenesis of Pteropine orthoreovirus (PRV) in BALB/c mice: Development of an animal infection model for PRV",http://dx.doi.org/10.1371/journal.pntd.0006076,PMC5730109,29240753,CC BY,"BACKGROUND: Cases of acute respiratory tract infection caused by Pteropine orthoreovirus (PRV) of the genus Orthoreovirus (family: Reoviridae) have been reported in Southeast Asia, where it was isolated from humans and bats. It is possible that PRV-associated respiratory infections might be prevalent in Southeast Asia. The clinical course of PRV is not fully elucidated. METHODS: The virulence, pathology, and pathogenesis of two PRV strains, a human-borne PRV strain (isolated from a patient, who returned to Japan from Bali, Indonesia in 2007) and a bat-borne PRV (isolated from a bat [Eonycteris spelaea] in the Philippines in 2013) were investigated in BALB/c mice using virological, pathological, and immunological study methods. RESULTS: The intranasal inoculation of BALB/c mice with human-borne PRV caused respiratory infection. In addition, all mice with immunity induced by pre-inoculation with a non-lethal dose of PRV were completely protected against lethal PRV infection. Mice treated with antiserum with neutralizing antibody activity after inoculation with a lethal dose of PRV showed a reduced fatality rate. In this mouse model, bat-borne PRV caused respiratory infection similar to human-borne PRV. PRV caused lethal respiratory disease in an animal model of PRV infection, in which BALB/c mice were used. CONCLUSIONS: The BALB/c mouse model might help to accelerate research on the virulence of PRV and be useful for evaluating the efficacy of therapeutic agents and vaccines for the treatment and prevention of PRV infection. PRV was shown for the first time to be a causative virus of respiratory disease on the basis of Koch’s postulations by the additional demonstration that PRV caused respiratory disease in mice through their intranasal inoculation with PRV.",2017 Dec 14,"['Egawa, Kazutaka', 'Shimojima, Masayuki', 'Taniguchi, Satoshi', 'Nagata, Noriyo', 'Tani, Hideki', 'Yoshikawa, Tomoki', 'Kurosu, Takeshi', 'Watanabe, Shumpei', 'Fukushi, Shuetsu', 'Saijo, Masayuki']",PLoS Negl Trop Dis,,,True
f9a383bf49414e8bd45d9068b73de803f980675a,PMC,A Simple Platform for the Rapid Development of Antimicrobials,http://dx.doi.org/10.1038/s41598-017-17941-7,PMC5730575,29242618,CC BY,"Recent infectious outbreaks highlight the need for platform technologies that can be quickly deployed to develop therapeutics needed to contain the outbreak. We present a simple concept for rapid development of new antimicrobials. The goal was to produce in as little as one week thousands of doses of an intervention for a new pathogen. We tested the feasibility of a system based on antimicrobial synbodies. The system involves creating an array of 100 peptides that have been selected for broad capability to bind and/or kill viruses and bacteria. The peptides are pre-screened for low cell toxicity prior to large scale synthesis. Any pathogen is then assayed on the chip to find peptides that bind or kill it. Peptides are combined in pairs as synbodies and further screened for activity and toxicity. The lead synbody can be quickly produced in large scale, with completion of the entire process in one week.",2017 Dec 14,"['Johnston, Stephen Albert', 'Domenyuk, Valeriy', 'Gupta, Nidhi', 'Batista, Milene Tavares', 'Lainson, John C.', 'Zhao, Zhan-Gong', 'Lusk, Joel F.', 'Loskutov, Andrey', 'Cichacz, Zbigniew', 'Stafford, Phillip', 'Legutki, Joseph Barten', 'Diehnelt, Chris W.']",Sci Rep,,,False
aca7ebdfaf454b97c94d94e2d4267f347b1d718d,PMC,A Simple Platform for the Rapid Development of Antimicrobials,http://dx.doi.org/10.1038/s41598-017-17941-7,PMC5730575,29242618,CC BY,"Recent infectious outbreaks highlight the need for platform technologies that can be quickly deployed to develop therapeutics needed to contain the outbreak. We present a simple concept for rapid development of new antimicrobials. The goal was to produce in as little as one week thousands of doses of an intervention for a new pathogen. We tested the feasibility of a system based on antimicrobial synbodies. The system involves creating an array of 100 peptides that have been selected for broad capability to bind and/or kill viruses and bacteria. The peptides are pre-screened for low cell toxicity prior to large scale synthesis. Any pathogen is then assayed on the chip to find peptides that bind or kill it. Peptides are combined in pairs as synbodies and further screened for activity and toxicity. The lead synbody can be quickly produced in large scale, with completion of the entire process in one week.",2017 Dec 14,"['Johnston, Stephen Albert', 'Domenyuk, Valeriy', 'Gupta, Nidhi', 'Batista, Milene Tavares', 'Lainson, John C.', 'Zhao, Zhan-Gong', 'Lusk, Joel F.', 'Loskutov, Andrey', 'Cichacz, Zbigniew', 'Stafford, Phillip', 'Legutki, Joseph Barten', 'Diehnelt, Chris W.']",Sci Rep,,,True
0330ede445d96dd0a27f474f945d6ce2e7085f15,PMC,Viperin Targets Flavivirus Virulence by Inducing Assembly of Noninfectious Capsid Particles,http://dx.doi.org/10.1128/JVI.01751-17,PMC5730767,29046456,CC BY,"Efficient antiviral immunity requires interference with virus replication at multiple layers targeting diverse steps in the viral life cycle. We describe here a novel flavivirus inhibition mechanism that results in interferon-mediated obstruction of tick-borne encephalitis virus particle assembly and involves release of malfunctioning membrane-associated capsid (C) particles. This mechanism is controlled by the activity of the interferon-induced protein viperin, a broad-spectrum antiviral interferon-stimulated gene. Through analysis of the viperin-interactome, we identified the Golgi brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1) as the cellular protein targeted by viperin. Viperin-induced antiviral activity, as well as C-particle release, was stimulated by GBF1 inhibition and knockdown and reduced by elevated levels of GBF1. Our results suggest that viperin targets flavivirus virulence by inducing the secretion of unproductive noninfectious virus particles via a GBF1-dependent mechanism. This as-yet-undescribed antiviral mechanism allows potential therapeutic intervention. IMPORTANCE The interferon response can target viral infection on almost every level; however, very little is known about the interference of flavivirus assembly. We show here that interferon, through the action of viperin, can disturb the assembly of tick-borne encephalitis virus. The viperin protein is highly induced after viral infection and exhibit broad-spectrum antiviral activity. However, the mechanism of action is still elusive and appears to vary between the different viruses, indicating that cellular targets utilized by several viruses might be involved. In this study, we show that viperin induces capsid particle release by interacting and inhibiting the function of the cellular protein Golgi brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1). GBF1 is a key protein in the cellular secretory pathway and is essential in the life cycle of many viruses, also targeted by viperin, implicating GBF1 as a novel putative drug target.",2017 Dec 14,"['Vonderstein, Kirstin', 'Nilsson, Emma', 'Hubel, Philipp', 'Nygård Skalman, Larsård', 'Upadhyay, Arunkumar', 'Pasto, Jenny', 'Pichlmair, Andreas', 'Lundmark, Richard', 'Överby, Anna K.']",J Virol,,,True
56948f3e281e7271f952181ed0c3bd83d1d70f8e,PMC,Interplay between Janus Kinase/Signal Transducer and Activator of Transcription Signaling Activated by Type I Interferons and Viral Antagonism,http://dx.doi.org/10.3389/fimmu.2017.01758,PMC5732261,29312301,CC BY,"Interferons (IFNs), which were discovered a half century ago, are a group of secreted proteins that play key roles in innate immunity against viral infection. The major signaling pathway activated by IFNs is the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, which leads to the expression of IFN-stimulated genes (ISGs), including many antiviral effectors. Viruses have evolved various strategies with which to antagonize the JAK/STAT pathway to influence viral virulence and pathogenesis. In recent years, notable progress has been made to better understand the JAK/STAT pathway activated by IFNs and antagonized by viruses. In this review, recent progress in research of the JAK/STAT pathway activated by type I IFNs, non-canonical STAT activation, viral antagonism of the JAK/STAT pathway, removing of the JAK/STAT antagonist from viral genome for attenuation, and the potential pathogenesis roles of tyrosine phosphorylation-independent non-canonical STATs activation during virus infection are discussed in detail. We expect that this review will provide new insight into the understanding the complexity of the interplay between JAK/STAT signaling and viral antagonism.",2017 Dec 11,"['Nan, Yuchen', 'Wu, Chunyan', 'Zhang, Yan-Jin']",Front Immunol,,,True
69e7ecb2ece358ef53df31c8ba497a183b007cc1,PMC,"Clinical, pathological, and molecular investigation of Mycoplasma pulmonis-induced murine respiratory mycoplasmosis in a rat (Rattus norvegicus) colony",http://dx.doi.org/10.14202/vetworld.2017.1378-1382,PMC5732346,29263602,CC BY,"AIM: Mycoplasma pulmonis (MP) remains potentially important rodent pathogen causing murine respiratory mycoplasmosis (MRM) which may go undiagnosed due to its asymptomatic nature. In the present study, we carried out clinical, pathological, and molecular investigations of MP-induced MRM in a rat colony. MATERIALS AND METHODS: Two female Wistar rats were observed to be diseased in animal facility of NISER, Bhubaneswar, and were kept in isolation for further investigation. Both the animals were found to be positive for MP after serological and molecular tests. Thereafter, whole rat colony comprising of 36 animals was segregated based on clinical symptoms and further sampled for histopathological, serological, and molecular investigations. Tracheal washing and infected lung tissue were collected during necropsy examination for DNA extraction. Molecular diagnosis was done by polymerase chain reaction (PCR) assay using species-specific primers. RESULT:: Classical symptoms of MP-associated respiratory tract infection were observed in only 2 of 36 infected animals, and most of the animals were found asymptomatic to the disease; however, all the animals were found to be carrier after necropsy and PCR assay. Gross and histopathological finding suggested severe congestion of the lungs along with suppurative and necrotizing pneumonia. The disease is confirmed by molecular diagnosis using species-specific primers in PCR assay. CONCLUSION: MRM may go undiagnosed due to asymptomatic nature. Detailed study of clinical symptoms, pathology, serology, and PCR-based molecular approach may aid in health monitoring and detection of MRM in a rodent colony reared for experimental purpose.",2017 Nov 25,"['Chawla, Saurabh', 'Jena, Sarita', 'Venkatsan, Balaji', 'Mahara, Kuna', 'Sahu, Nilanjan']",Vet World,,,True
93d080273b1f33330243dd140a35ba890ddd2973,PMC,The determinants and consequences of adult nursing staff turnover: a systematic review of systematic reviews,http://dx.doi.org/10.1186/s12913-017-2707-0,PMC5732502,29246221,CC BY,"BACKGROUND: Nurses leaving their jobs and the profession are an issue of international concern, with supply-demand gaps for nurses reported to be widening. There is a large body of existing literature, much of which is already in review form. In order to advance the usefulness of the literature for nurse and human resource managers, we undertook an overview (review of systematic reviews). The aim of the overview was to identify high quality evidence of the determinants and consequences of turnover in adult nursing. METHODS: Reviews were identified which were published between 1990 and January 2015 in English using electronic databases (the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE, Applied Social Sciences Index and Abstracts, CINAHL plus and SCOPUS) and forward searching. All stages of the review were conducted in parallel by two reviewers. Reviews were quality appraised using the Assessment of Multiple Systematic Reviews and their findings narratively synthesised. RESULTS: Nine reviews were included. We found that the current evidence is incomplete and has a number of important limitations. However, a body of moderate quality review evidence does exist giving a picture of multiple determinants of turnover in adult nursing, with - at the individual level - nurse stress and dissatisfaction being important factors and -at the organisational level - managerial style and supervisory support factors holding most weight. The consequences of turnover are only described in economic terms, but are considered significant. CONCLUSIONS: In making a quality assessment of the review as well as considering the quality of the included primary studies and specificity in the outcomes they measure, the overview found that the evidence is not as definitive as previously presented from individual reviews. Further research is required, of rigorous research design, whether quantitative or qualitative, particularly against the outcome of actual turnover as opposed to intention to leave. TRIAL REGISTRATION: PROSPERO Registration 17 March 2015: CRD42015017613. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12913-017-2707-0) contains supplementary material, which is available to authorized users.",2017 Dec 15,"['Halter, Mary', 'Boiko, Olga', 'Pelone, Ferruccio', 'Beighton, Carole', 'Harris, Ruth', 'Gale, Julia', 'Gourlay, Stephen', 'Drennan, Vari']",BMC Health Serv Res,,,True
7da4fcd53b89c33706e7e63f8b2f527f27f07ef8,PMC,Characterization of plasma proteins in children of different Mycobacterium tuberculosis infection status using label-free quantitative proteomics,http://dx.doi.org/10.18632/oncotarget.21179,PMC5732728,29262562,CC BY,"Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is an infectious disease found worldwide. Children infected with MTB are more likely to progress to active TB (ATB); however, the molecular mechanism behind this process has long been a mystery. We employed the label-free quantitative proteomic technology to identify and characterize differences in plasma proteins between ATB and latent TB infection (LTBI) in children. To detect differences that are indicative of MTB infection, we first selected proteins whose expressions were markedly different between the ATB and LTBI groups and the control groups (inflammatory disease control (IDC) and healthy control (HC) groups). A total of 521 proteins differed (> 1.5-fold or < 0.6-fold) in the LTBI group, and 318 proteins in the ATB group when compared with the control groups. Of these, 49 overlapping proteins were differentially expressed between LTBI and ATB. Gene Ontology (GO) analysis revealed most proteins had a cellular and organelle distribution. The MTB infection status was mainly related to differences in binding, cellular and metabolic processes. XRCC4, PCF11, SEMA4A and ATP11A were selected and further verified by qPCR and western blot. At the mRNA level, the expression of XRCC4, PCF11and SEMA4A presented an increased trend in ATB group compare with LTBI. At the protein level, the expression of all these proteins by western blot in ATB/LTBI was consistent with the trends from proteomic detection. Our results provide important data for future mechanism studies and biomarker selection for MTB infection in children.",2017 Sep 23,"['Li, Jieqiong', 'Sun, Lin', 'Xu, Fang', 'Xiao, Jing', 'Jiao, Weiwei', 'Qi, Hui', 'Shen, Chen', 'Shen, Adong']",Oncotarget,,,True
9e9966ccdc8b61b6de46f5348e4b09e7fffe60b4,PMC,Characterization of plasma proteins in children of different Mycobacterium tuberculosis infection status using label-free quantitative proteomics,http://dx.doi.org/10.18632/oncotarget.21179,PMC5732728,29262562,CC BY,"Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is an infectious disease found worldwide. Children infected with MTB are more likely to progress to active TB (ATB); however, the molecular mechanism behind this process has long been a mystery. We employed the label-free quantitative proteomic technology to identify and characterize differences in plasma proteins between ATB and latent TB infection (LTBI) in children. To detect differences that are indicative of MTB infection, we first selected proteins whose expressions were markedly different between the ATB and LTBI groups and the control groups (inflammatory disease control (IDC) and healthy control (HC) groups). A total of 521 proteins differed (> 1.5-fold or < 0.6-fold) in the LTBI group, and 318 proteins in the ATB group when compared with the control groups. Of these, 49 overlapping proteins were differentially expressed between LTBI and ATB. Gene Ontology (GO) analysis revealed most proteins had a cellular and organelle distribution. The MTB infection status was mainly related to differences in binding, cellular and metabolic processes. XRCC4, PCF11, SEMA4A and ATP11A were selected and further verified by qPCR and western blot. At the mRNA level, the expression of XRCC4, PCF11and SEMA4A presented an increased trend in ATB group compare with LTBI. At the protein level, the expression of all these proteins by western blot in ATB/LTBI was consistent with the trends from proteomic detection. Our results provide important data for future mechanism studies and biomarker selection for MTB infection in children.",2017 Sep 23,"['Li, Jieqiong', 'Sun, Lin', 'Xu, Fang', 'Xiao, Jing', 'Jiao, Weiwei', 'Qi, Hui', 'Shen, Chen', 'Shen, Adong']",Oncotarget,,,False
18f3b3f9f77227f4941079cdb605af4e5777c061,PMC,Novel Identified HLA-A*0201-Restricted Hantaan Virus Glycoprotein Cytotoxic T-Cell Epitopes Could Effectively Induce Protective Responses in HLA-A2.1/K(b) Transgenic Mice May Associate with the Severity of Hemorrhagic Fever with Renal Syndrome,http://dx.doi.org/10.3389/fimmu.2017.01797,PMC5732971,29312318,CC BY,"Hantaan virus (HTNV) infections can cause severe hemorrhagic fever with renal syndrome (HFRS) in humans, which is associated with high fatality rates. Cytotoxic T cell (CTL) responses contribute to virus elimination; however, to date, HLA class I allele-restricted HTNV glycoprotein (GP) epitopes recognized by CTLs have not been reported, limiting our understanding of CTL responses against HTNV infection in humans. In this study, 34 HTNV GP nine-mer epitopes that may bind to HLA-A*0201 molecules were predicted using the BIMAS and SYFPEITHI database. Seven of the epitopes were demonstrated to bind to HLA-A*0201 molecules with high affinity via the T2 cell binding assay and were successfully used to synthesize peptide/HLA-A*0201 tetramers. The results of tetramer staining showed that the frequencies of each epitope-specific CTL were higher in patients with milder HFRS, which indicated that the epitopes may induce protective CTL responses after HTNV infection. IFN-γ-enzyme-linked immunospot analysis further confirmed the immunoreactivity of epitopes by eliciting epitope-specific IFN-γ-producing CTL responses. In an HTNV challenge trial, significant inhibition of HTNV replication characterized by lower levels of antigens and RNA loads was observed in major target organs (liver, spleen, and kidneys) of HLA-A2.1/K(b) transgenic mice pre-vaccinated with nonapeptides VV9 (aa8–aa16, VMASLVWPV), SL9 (aa996–aa1004, SLTECPTFL) and LL9 (aa358–aa366, LIWTGMIDL). Importantly, LL9 exhibited the best ability to induce protective CTL responses and showed a prominent effect on the kidneys, potentially preventing kidney injury after HTNV infection. Taken together, our results highlight that HTNV GP-derived HLA-A*0201-restricted epitopes could elicit protective CTL responses against the virus, and that epitope LL9 functions as an immunodominant protective epitope that may advance the design of safe and effective CTL-based HTNV peptide vaccines for humans.",2017 Dec 12,"['Tang, Kang', 'Cheng, Linfeng', 'Zhang, Chunmei', 'Zhang, Yusi', 'Zheng, Xuyang', 'Zhang, Yun', 'Zhuang, Ran', 'Jin, Boquan', 'Zhang, Fanglin', 'Ma, Ying']",Front Immunol,,,True
283604cd89c223271768c0a2fb065cba3a015b13,PMC,Development of a Quantitative Loop-Mediated Isothermal Amplification Assay for the Rapid Detection of Novel Goose Parvovirus,http://dx.doi.org/10.3389/fmicb.2017.02472,PMC5732990,29312182,CC BY,"An infectious disease characterized with short bills and protruding tongues has attacked to meat ducks in China since March 2015, which has caused ducks poor growth and enormous economic losses to duck industry of China. It was eventually proved to be caused by parvovirus after pathogen isolation and identification. As the genomic sequence analysis showed, this pathogen shared 90.8–94.6% of nucleotide identity with goose parvovirus (GPV), and it was called duck-origin novel goose parvovirus (N-GPV). In this study, a quantitative loop-mediated isothermal amplification (qLAMP) assay was developed for the rapid diagnosis of N-GPV. A set of four specific primers, two inner and two outer, were designed targeting at VP3 gene, which could be completed within 60 min at 65°C in water bath or on a real-time PCR instrument for quantitative analysis. Specificity test of LAMP assay showed that there was no cross-reactivity between N-GPV and other duck pathogens, and the detection limit of qLAMP assay was 1.0 × 10(2) copies/μL. The repeatability of this method was confirmed by inter-assay and intra-assay tests with variability ranging from 0.74 to 2.25%. The results have indicated that the qLAMP assay was a simple, rapid, accurate, sensitive, and specific method for detecting N-GPV, especially on field detection.",2017 Dec 12,"['Yang, Jing', 'Chen, Hao', 'Wang, Zhenzhong', 'Yu, Xianglong', 'Niu, Xiaoyu', 'Tang, Yi', 'Diao, Youxiang']",Front Microbiol,,,True
b54932936d9dd6f8a399f23e19d0a1d0aeabd954,PMC,Markers and Biomarkers of Endothelium: When Something Is Rotten in the State,http://dx.doi.org/10.1155/2017/9759735,PMC5733214,29333215,CC BY,"Endothelium is a community of endothelial cells (ECs), which line the blood and lymphatic vessels, thus forming an interface between the tissues and the blood or lympha. This strategic position of endothelium infers its indispensable functional role in controlling vasoregulation, haemostasis, and inflammation. The state of endothelium is simultaneously the cause and effect of many diseases, and this is coupled with modifications of endothelial phenotype represented by markers and with biochemical profile of blood represented by biomarkers. In this paper, we briefly review data on the functional role of endothelium, give definitions of endothelial markers and biomarkers, touch on the methodological approaches for revealing biomarkers, present an implicit role of endothelium in some toxicological mechanistic studies, and survey the role of reactive oxygen species (ROS) in modulation of endothelial status.",2017 Nov 23,"['Goncharov, Nikolay V.', 'Nadeev, Alexander D.', 'Jenkins, Richard O.', 'Avdonin, Pavel V.']",Oxid Med Cell Longev,,,True
165cfcb6f439f6d779d1e94b0b8a3db96c79b22e,PMC,"Healthcare worker infected with Middle East Respiratory Syndrome during cardiopulmonary resuscitation in Korea, 2015",http://dx.doi.org/10.4178/epih.e2017052,PMC5733382,29129042,CC BY,"OBJECTIVES: During the outbreak of the Middle East Respiratory Syndrome (MERS) in Korea in 2015, the Korea Centers for Disease Control and Prevention (KCDC) confirmed a case of MERS in a healthcare worker in Daejeon, South Korea. To verify the precise route of infection for the case, we conducted an in-depth epidemiological investigation in cooperation with the KCDC. METHODS: We reviewed the MERS outbreak investigation report of the KCDC, and interviewed the healthcare worker who had recovered from MERS. Using the media interview data, we reaffirmed and supplemented the nature of the exposure. RESULTS: The healthcare worker, a nurse, was infected while performing cardiopulmonary resuscitation (CPR) for a MERS patient in an isolation room. During the CPR which lasted for an hour, a large amount of body fluid was splashed. The nurse was presumed to have touched the mask to adjust its position during the CPR. She suggested that she was contaminated with the MERS patient’s body fluids by wiping away the sweat from her face during the CPR. CONCLUSIONS: The possible routes of infection may include the following: respiratory invasion of aerosols contaminated with MERS-coronavirus (MERS-CoV) through a gap between the face and mask; mucosal exposure to sweat contaminated with MERS-CoV; and contamination during doffing of personal protective equipment. The MERS guidelines should reflect this case to decrease the risk of infection during CPR.",2017 Nov 12,"['Nam, Hae-Sung', 'Yeon, Mi-Yeon', 'Park, Jung Wan', 'Hong, Jee-Young', 'Son, Ji Woong']",Epidemiol Health,,,True
e7e0c619c9f078101beffb8b3822c65e95995856,PMC,"Healthcare worker infected with Middle East Respiratory Syndrome during cardiopulmonary resuscitation in Korea, 2015",http://dx.doi.org/10.4178/epih.e2017052,PMC5733382,29129042,CC BY,"OBJECTIVES: During the outbreak of the Middle East Respiratory Syndrome (MERS) in Korea in 2015, the Korea Centers for Disease Control and Prevention (KCDC) confirmed a case of MERS in a healthcare worker in Daejeon, South Korea. To verify the precise route of infection for the case, we conducted an in-depth epidemiological investigation in cooperation with the KCDC. METHODS: We reviewed the MERS outbreak investigation report of the KCDC, and interviewed the healthcare worker who had recovered from MERS. Using the media interview data, we reaffirmed and supplemented the nature of the exposure. RESULTS: The healthcare worker, a nurse, was infected while performing cardiopulmonary resuscitation (CPR) for a MERS patient in an isolation room. During the CPR which lasted for an hour, a large amount of body fluid was splashed. The nurse was presumed to have touched the mask to adjust its position during the CPR. She suggested that she was contaminated with the MERS patient’s body fluids by wiping away the sweat from her face during the CPR. CONCLUSIONS: The possible routes of infection may include the following: respiratory invasion of aerosols contaminated with MERS-coronavirus (MERS-CoV) through a gap between the face and mask; mucosal exposure to sweat contaminated with MERS-CoV; and contamination during doffing of personal protective equipment. The MERS guidelines should reflect this case to decrease the risk of infection during CPR.",2017 Nov 12,"['Nam, Hae-Sung', 'Yeon, Mi-Yeon', 'Park, Jung Wan', 'Hong, Jee-Young', 'Son, Ji Woong']",Epidemiol Health,,,True
e204da6f7d00469d696968ce521afce85abcb16d,PMC,Identifying volatile metabolite signatures for the diagnosis of bacterial respiratory tract infection using electronic nose technology: A pilot study,http://dx.doi.org/10.1371/journal.pone.0188879,PMC5734722,29252995,CC BY,"OBJECTIVES: New point of care diagnostics are urgently needed to reduce the over-prescription of antimicrobials for bacterial respiratory tract infection (RTI). We performed a pilot cross sectional study to assess the feasibility of gas-capillary column ion mobility spectrometer (GC-IMS), for the analysis of volatile organic compounds (VOC) in exhaled breath to diagnose bacterial RTI in hospital inpatients. METHODS: 71 patients were prospectively recruited from the Acute Medical Unit of the Royal Liverpool University Hospital between March and May 2016 and classified as confirmed or probable bacterial or viral RTI on the basis of microbiologic, biochemical and radiologic testing. Breath samples were collected at the patient’s bedside directly into the electronic nose device, which recorded a VOC spectrum for each sample. Sparse principal component analysis and sparse logistic regression were used to develop a diagnostic model to classify VOC spectra as being caused by bacterial or non-bacterial RTI. RESULTS: Summary area under the receiver operator characteristic curve was 0.73 (95% CI 0.61–0.86), summary sensitivity and specificity were 62% (95% CI 41–80%) and 80% (95% CI 64–91%) respectively (p = 0.00147). CONCLUSIONS: GC-IMS analysis of exhaled VOC for the diagnosis of bacterial RTI shows promise in this pilot study and further trials are warranted to assess this technique.",2017 Dec 18,"['Lewis, Joseph M.', 'Savage, Richard S.', 'Beeching, Nicholas J.', 'Beadsworth, Mike B. J.', 'Feasey, Nicholas', 'Covington, James A.']",PLoS One,,,True
b6f6aee927db36fcefbc96af78e21ac7d0059b4f,PMC,Downregulation of monocytic differentiation via modulation of CD147 by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors,http://dx.doi.org/10.1371/journal.pone.0189701,PMC5734787,29253870,CC0,"CD147 is an activation induced glycoprotein that promotes the secretion and activation of matrix metalloproteinases (MMPs) and is upregulated during the differentiation of macrophages. Interestingly, some of the molecular functions of CD147 rely on its glycosylation status: the highly glycosylated forms of CD147 induce MMPs whereas the lowly glycosylated forms inhibit MMP activation. Statins are hydroxy-methylglutaryl coenzyme A reductase inhibitors that block the synthesis of mevalonate, thereby inhibiting all mevalonate-dependent pathways, including isoprenylation, N-glycosylation and cholesterol synthesis. In this study, we investigated the role of statins in the inhibition of macrophage differentiation and the associated process of MMP secretion through modulation of CD147. We observed that differentiation of the human monocytic cell line THP-1 to a macrophage phenotype led to upregulation of CD147 and CD14 and that this effect was inhibited by statins. At the molecular level, statins altered CD147 expression, structure and function by inhibiting isoprenylation and N-glycosylation. In addition, statins induced a shift of CD147 from its highly glycosylated form to its lowly glycosylated form. This shift in N-glycosylation status was accompanied by a decrease in the production and functional activity of MMP-2 and MMP-9. In conclusion, these findings describe a novel molecular mechanism of immune regulation by statins, making them interesting candidates for autoimmune disease therapy.",2017 Dec 18,"['Sasidhar, Manda V.', 'Chevooru, Sai Krishnaveni', 'Eickelberg, Oliver', 'Hartung, Hans-Peter', 'Neuhaus, Oliver']",PLoS One,,,True
00352a58c8766861effed18a4b079d1683fec2ec,PMC,Function of the Deubiquitinating Enzyme USP46 in the Nervous System and Its Regulation by WD40-Repeat Proteins,http://dx.doi.org/10.3389/fnsyn.2017.00016,PMC5735123,29302259,CC BY,"Posttranslational modification of proteins by ubiquitin regulates synapse development and synaptic transmission. Much progress has been made investigating the role of ubiquitin ligases at the synapse, however very little is known about the deubiquitinating enzymes (DUBs) which remove ubiquitin from target proteins. Although there are far fewer DUBs than ubiquitin ligases encoded by the human genome, it is becoming clear that DUBs have very specific physiological functions, suggesting that DUB activity is tightly regulated in vivo. Many DUBs function as part of larger protein complexes, and multiple regulatory mechanisms exist to control the expression, localization and catalytic activity of DUBs. In this review article, we focus on the role of the DUB USP46 in the nervous system, and illustrate potential mechanisms of regulating DUBs by describing how USP46 is regulated by two WD40-repeat (WDR) proteins, WDR48/UAF1 and WDR20, based on recent structural studies and genetic analyses in vivo.",2017 Dec 14,"['Hodul, Molly', 'Dahlberg, Caroline L.', 'Juo, Peter']",Front Synaptic Neurosci,,,True
29d98c8c19182d261f0f0fd59e09dd466cfcaade,PMC,Evaluation of a field-deployable reverse transcription-insulated isothermal PCR for rapid and sensitive on-site detection of Zika virus,http://dx.doi.org/10.1186/s12879-017-2852-4,PMC5735522,29258444,CC BY,"BACKGROUND: The recent emergence of Zika virus (ZIKV) in Brazil and its precipitous expansion throughout the Americas has highlighted the urgent need for a rapid and reliable on-site diagnostic assay suitable for viral detection. Such point-of-need (PON), low-cost diagnostics are essential for ZIKV control in vulnerable areas with limited resources. METHODS: We developed and evaluated a ZIKV-specific field-deployable RT-iiPCR reagent set targeting the E gene for rapid detection of ZIKV in ZIKV-spiked human and mosquito specimens, and compared its performance to the Center for Disease Control and Prevention (CDC) and Pan American Health Organization (PAHO) RT-qPCR assays targeting the E and NS2B genes, respectively. RESULTS: These assays demonstrated exclusive specificity for ZIKV (African and Asian lineages), had limits of detection ranging from 10 to 100 in vitro transcribed RNA copies/μl and detection endpoints at 10 plaque forming units/ml of infectious tissue culture fluid. Analysis of human whole blood, plasma, serum, semen, urine, and mosquito pool samples spiked with ZIKV showed an agreement of 90% (k = 0.80), 92% (k = 0.82), 95% (k = 0.86), 92% (k = 0.81), 90% (k = 0.79), and 100% (k = 1), respectively, between the RT-iiPCR assay and composite results from the reference RT-qPCR assays. Overall, the concurrence between the ZIKV RT-iiPCR and the reference RT-qPCR assays was 92% (k = 0.83). CONCLUSIONS: The ZIKV RT-iiPCR has a performance comparable to the reference CDC and PAHO RT-qPCR assays but provides much faster results (~1.5 h) with a field-deployable system that can be utilized as a PON diagnostic with the potential to significantly improve the quality of the health care system in vulnerable areas. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-017-2852-4) contains supplementary material, which is available to authorized users.",2017 Dec 19,"['Carossino, Mariano', 'Li, Yanqiu', 'Lee, Pei-Yu A.', 'Tsai, Chuan-Fu', 'Chou, Pin-Hsing', 'Williams, Dennis', 'Skillman, Ashley', 'Frank Cook, R.', 'Brown, Grayson', 'Chang, Hsiao-Fen G.', 'Wang, Hwa-Tang T.', 'Balasuriya, Udeni B. R.']",BMC Infect Dis,,,True
d0f3b9b638c07e1becd5d360d890349f4ff6a8ec,PMC,Respiratory Tract Viral Infections and Coinfections Identified by Anyplex™ II RV16 Detection Kit in Pediatric Patients at a Riyadh Tertiary Care Hospital,http://dx.doi.org/10.1155/2017/1928795,PMC5735607,29359144,CC BY,"Respiratory infections are caused by an array of viruses, and limited information is available about viral coexistence, comparative symptoms, and the burden of illness. This retrospective cohort study aimed to determine the etiological agents responsible for respiratory tract infections by Anyplex II RV16 detection kit (RV16, Seegene), involving 2266 pediatric patients with respiratory infections admitted to the Department of Pediatrics at King Abdul-Aziz Medical City, Ministry of National Guard, Riyadh, from July 2014 to June 2015. The most frequent respiratory infections were recorded in the 1 to 5 year age group (44.7%). Rhinovirus (32.5%), Adenovirus (16.9%), and Respiratory syncytial virus (RSV) B (10.4%) were most common. In single viral infections, Rhinovirus (41.2%), Metapneumovirus (15.3%), and Bocavirus (13.7%) were most frequent. In multiple viral infections, Rhinovirus (36.7%), Adenovirus (35.2%), Bocavirus (11.2), RSV B (7.8%), and RSV A (6.7%) were most frequent. No significant difference was observed in clinical presentations; however, rhinorrhea and hypodynamia were significantly associated with viral respiratory infections. Most respiratory viral pathogens peaked during December, January, March, and April. Rhinovirus, Adenovirus, and Bocavirus circulations were detected throughout the year. Winter peaks were recorded for Rhinovirus, RSV B, Adenovirus, and RSV A, whereas the Metapneumovirus, and the Bocavirus peaked in March and April. These findings enhance understanding of viral etiology and distribution to improve respiratory infection management and treatment.",2017 Nov 21,"['Eifan, Saleh A.', 'Hanif, Atif', 'AlJohani, Sameera Mohammed', 'Atif, Muhammad']",Biomed Res Int,,,True
a1ebd42a27d62df715e134e72bc0556a794c2270,PMC,Development of global health research in China,http://dx.doi.org/10.7189/jogh.07.020102,PMC5735772,29302308,CC BY,,,"Guo, Yan",J Glob Health.; 7(2):020102,,,False
a36b65d00944ef78c5bc2b7bf759122c2ac4eaf1,PMC,Detection and full genome characterization of two beta CoV viruses related to Middle East respiratory syndrome from bats in Italy,http://dx.doi.org/10.1186/s12985-017-0907-1,PMC5735805,29258555,CC BY,"BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV), which belongs to beta group of coronavirus, can infect multiple host species and causes severe diseases in humans. Multiple surveillance and phylogenetic studies suggest a bat origin. In this study, we describe the detection and full genome characterization of two CoVs closely related to MERS-CoV from two Italian bats, Pipistrellus kuhlii and Hypsugo savii. METHODS: Pool of viscera were tested by a pan-coronavirus RT-PCR. Virus isolation was attempted by inoculation in different cell lines. Full genome sequencing was performed using the Ion Torrent platform and phylogenetic trees were performed using IQtree software. Similarity plots of CoV clade c genomes were generated by using SSE v1.2. The three dimensional macromolecular structure (3DMMS) of the receptor binding domain (RBD) in the S protein was predicted by sequence-homology method using the protein data bank (PDB). RESULTS: Both samples resulted positive to the pan-coronavirus RT-PCR (IT-batCoVs) and their genome organization showed identical pattern of MERS CoV. Phylogenetic analysis showed a monophyletic group placed in the Beta2c clade formed by MERS-CoV sequences originating from humans and camels and bat-related sequences from Africa, Italy and China. The comparison of the secondary and 3DMMS of the RBD of IT-batCoVs with MERS, HKU4 and HKU5 bat sequences showed two aa deletions located in a region corresponding to the external subdomain of MERS-RBD in IT-batCoV and HKU5 RBDs. CONCLUSIONS: This study reported two beta CoVs closely related to MERS that were obtained from two bats belonging to two commonly recorded species in Italy (P. kuhlii and H. savii). The analysis of the RBD showed similar structure in IT-batCoVs and HKU5 respect to HKU4 sequences. Since the RBD domain of HKU4 but not HKU5 can bind to the human DPP4 receptor for MERS-CoV, it is possible to suggest also for IT-batCoVs the absence of DPP4-binding potential. More surveillance studies are needed to better investigate the potential intermediate hosts that may play a role in the interspecies transmission of known and currently unknown coronaviruses with particular attention to the S protein and the receptor specificity and binding affinity.",2017 Dec 19,"['Moreno, Ana', 'Lelli, Davide', 'de Sabato, Luca', 'Zaccaria, Guendalina', 'Boni, Arianna', 'Sozzi, Enrica', 'Prosperi, Alice', 'Lavazza, Antonio', 'Cella, Eleonora', 'Castrucci, Maria Rita', 'Cicozzi, Massimo', 'Vaccari, Gabriele']",Virol J,,,True
8075ec44f23c7e5702d77169758cf1e5fea53b4f,PMC,Recombinant influenza H9N2 virus with a substitution of H3 hemagglutinin transmembrane domain showed enhanced immunogenicity in mice and chicken,http://dx.doi.org/10.1038/s41598-017-18054-x,PMC5738434,29263359,CC BY,"In recent years, avian influenza virus H9N2 undergoing antigenic drift represents a threat to poultry farming as well as public health. Current vaccines are restricted to inactivated vaccine strains and their related variants. In this study, a recombinant H9N2 (H9N2-TM) strain with a replaced H3 hemagglutinin (HA) transmembrane (TM) domain was generated. Virus assembly and viral protein composition were not affected by the transmembrane domain replacement. Further, the recombinant TM-replaced H9N2-TM virus could provide better inter-clade protection in both mice and chickens against H9N2, suggesting that the H3-TM-replacement could be considered as a strategy to develop efficient subtype-specific H9N2 influenza vaccines.",2017 Dec 20,"['Zhang, Yun', 'Wei, Ying', 'Liu, Kang', 'Huang, Mengjiao', 'Li, Ran', 'Wang, Yang', 'Liu, Qiliang', 'Zheng, Jing', 'Xue, Chunyi', 'Cao, Yongchang']",Sci Rep,,,False
1c39727d1bf8a4e67e43fccecf8dafcd9b960b70,PMC,Recombinant influenza H9N2 virus with a substitution of H3 hemagglutinin transmembrane domain showed enhanced immunogenicity in mice and chicken,http://dx.doi.org/10.1038/s41598-017-18054-x,PMC5738434,29263359,CC BY,"In recent years, avian influenza virus H9N2 undergoing antigenic drift represents a threat to poultry farming as well as public health. Current vaccines are restricted to inactivated vaccine strains and their related variants. In this study, a recombinant H9N2 (H9N2-TM) strain with a replaced H3 hemagglutinin (HA) transmembrane (TM) domain was generated. Virus assembly and viral protein composition were not affected by the transmembrane domain replacement. Further, the recombinant TM-replaced H9N2-TM virus could provide better inter-clade protection in both mice and chickens against H9N2, suggesting that the H3-TM-replacement could be considered as a strategy to develop efficient subtype-specific H9N2 influenza vaccines.",2017 Dec 20,"['Zhang, Yun', 'Wei, Ying', 'Liu, Kang', 'Huang, Mengjiao', 'Li, Ran', 'Wang, Yang', 'Liu, Qiliang', 'Zheng, Jing', 'Xue, Chunyi', 'Cao, Yongchang']",Sci Rep,,,True
8a016307c6c178384d6819b68cab3b1045486b9a,PMC,Risk of mortality associated with respiratory syncytial virus and influenza infection in adults,http://dx.doi.org/10.1186/s12879-017-2897-4,PMC5738863,29262784,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) infection constitutes a substantial disease burden in the general population. However, the risk of death for RSV infection has been rarely evaluated with confounders or comorbidities adjusted. We aimed to evaluate whether RSV infection is associated with higher mortality than seasonal influenza after adjusting for confounders and comorbidities and the effect of oseltamivir on the mortality in patients with influenza infection. METHODS: A retrospective cohort study was conducted on adult (≥18 years) patients admitted to the emergency department and ward of a university teaching hospital for suspected viral infection during 2013–2015 (N = 3743). RSV infection was diagnosed by multiplex PCR (N = 87). Adults hospitalized for seasonal influenza during the study period were enrolled as a comparison group (n = 312). The main outcome was 20-day all-cause mortality.We used Cox proportional hazard regression analyses to calculate the relative risk of death. RESULTS: Adult patients were less likely to be diagnosed with RSV than with influenza (2.3 vs 8.3%, respectively), were older and more likely to be diagnosed with pneumonia, chronic obstructive pulmonary disease, hypoxemia, and bacterial co-infection. In patients with RSV infection, the 20-day all-cause mortality was higher than that for influenza, (18.4 vs 6.7%, respectively). RSV infection showed significantly higher risk of death compared to the seasonal influenza group, with hazard ratio, 2.32 (95% CI, 1.17–4.58). Oseltamivir had no significant effect on mortality in patients with influenza. CONCLUSIONS: RSV infection was significantly associated with a higher risk of death than seasonal influenza, adjusted for potential confounders and comorbidities.",2017 Dec 20,"['Kwon, Yong Shik', 'Park, Sun Hyo', 'Kim, Mi-Ae', 'Kim, Hyun Jung', 'Park, Jae Seok', 'Lee, Mi Young', 'Lee, Choong Won', 'Dauti, Sonila', 'Choi, Won-Il']",BMC Infect Dis,,,True
1f7224df292f2dcbfb805602296acd9aba317f24,PMC,"Indirubin, a bisindole alkaloid from Isatis indigotica, reduces H1N1 susceptibility in stressed mice by regulating MAVS signaling",http://dx.doi.org/10.18632/oncotarget.22350,PMC5739664,29285277,CC BY,"Isatis indigotica has a long history in treating virus infection and related symptoms in China. Nevertheless, its antivirus evidence in animal studies is not satisfactory, which might be due to the lack of appropriate animal model. Previously, we had utilized restraint stress to establish mouse H1N1 susceptibility model which was helpful in evaluating the anti-virus effect of medicines targeting host factors, such as type I interferon production. In this study, this model was employed to investigate the effect and mechanism of indirubin, a natural bisindole alkaloid from Isatis indigotica, on influenza A virus susceptibility. In the in vitro study, the stress hormone corticosterone was used to simulate restraint stress. Our results demonstrated that indirubin decreased the susceptibility to influenza virus with lowered mortality and alleviated lung damage in restraint-stressed mice model. Moreover, indirubin promoted the expression of interferon-β and interferon inducible transmembrane 3. In addition, indirubin maintained the morphology and function of mitochondria following influenza A virus infection. Further study revealed that indirubin promoted interferon-β production through promoting mitochondrial antiviral signaling pathway. Our study indicated that indirubin could be a candidate for the therapy of influenza.",2017 Nov 9,"['Jie, Chong', 'Luo, Zhuo', 'Chen, Huan', 'Wang, Min', 'Yan, Chang', 'Mao, Zhong-Fu', 'Xiao, Gao-Keng', 'Kurihara, Hiroshi', 'Li, Yi-Fang', 'He, Rong-Rong']",Oncotarget,,,True
070ed9d7ad3ba35df48652f7fe255bf7a53325c5,PMC,"miRNA-36 inhibits KSHV, EBV, HSV-2 infection of cells via stifling expression of interferon induced transmembrane protein 1 (IFITM1)",http://dx.doi.org/10.1038/s41598-017-18225-w,PMC5740118,29269892,CC BY,"Kaposi’s sarcoma-associated herpesvirus (KSHV) is etiologically associated with all forms of Kaposi’s sarcoma worldwide. Little is currently known about the role of microRNAs (miRNAs) in KSHV entry. We recently demonstrated that KSHV induces a plethora of host cell miRNAs during the early stages of infection. In this study, we show the ability of host cell novel miR-36 to specifically inhibit KSHV-induced expression of interferon induced transmembrane protein 1 (IFITM1) to limit virus infection of cells. Transfecting cells with miR-36 mimic specifically lowered IFITM1 expression and thereby significantly dampening KSHV infection. In contrast, inhibition of miR-36 using miR-36 inhibitor had the direct opposite effect on KSHV infection of cells, allowing enhanced viral infection of cells. The effect of miR-36 on KSHV infection of cells was at a post-binding stage of virus entry. The highlight of this work was in deciphering a common theme in the ability of miR-36 to regulate infection of closely related DNA viruses: KSHV, Epstein-Barr virus (EBV), and herpes simplexvirus-2 (HSV-2). Taken together, we report for the first time the ability of host cell miRNA to regulate internalization of KSHV, EBV, and HSV-2 in hematopoietic and endothelial cells.",2017 Dec 21,"['Hussein, Hosni A. M.', 'Akula, Shaw M.']",Sci Rep,,,False
7ee798b6104d800e4c3aee14cec31ada51dd26c7,PMC,"miRNA-36 inhibits KSHV, EBV, HSV-2 infection of cells via stifling expression of interferon induced transmembrane protein 1 (IFITM1)",http://dx.doi.org/10.1038/s41598-017-18225-w,PMC5740118,29269892,CC BY,"Kaposi’s sarcoma-associated herpesvirus (KSHV) is etiologically associated with all forms of Kaposi’s sarcoma worldwide. Little is currently known about the role of microRNAs (miRNAs) in KSHV entry. We recently demonstrated that KSHV induces a plethora of host cell miRNAs during the early stages of infection. In this study, we show the ability of host cell novel miR-36 to specifically inhibit KSHV-induced expression of interferon induced transmembrane protein 1 (IFITM1) to limit virus infection of cells. Transfecting cells with miR-36 mimic specifically lowered IFITM1 expression and thereby significantly dampening KSHV infection. In contrast, inhibition of miR-36 using miR-36 inhibitor had the direct opposite effect on KSHV infection of cells, allowing enhanced viral infection of cells. The effect of miR-36 on KSHV infection of cells was at a post-binding stage of virus entry. The highlight of this work was in deciphering a common theme in the ability of miR-36 to regulate infection of closely related DNA viruses: KSHV, Epstein-Barr virus (EBV), and herpes simplexvirus-2 (HSV-2). Taken together, we report for the first time the ability of host cell miRNA to regulate internalization of KSHV, EBV, and HSV-2 in hematopoietic and endothelial cells.",2017 Dec 21,"['Hussein, Hosni A. M.', 'Akula, Shaw M.']",Sci Rep,,,True
a7f47a771ace5d75afbd36064bb1a843f9821f83,PMC,The persistence of multiple strains of avian influenza in live bird markets,http://dx.doi.org/10.1098/rspb.2017.0715,PMC5740266,29212718,CC BY,"Multiple subtypes of avian influenza (AI) and novel reassortants are frequently isolated from live bird markets (LBMs). However, our understanding of the drivers of persistence of multiple AI subtypes is limited. We propose a stochastic model of AI transmission within an LBM that incorporates market size, turnover rate and the balance of direct versus environmental transmissibility. We investigate the relationship between these factors and the critical community size (CCS) for the persistence of single and multiple AI strains within an LBM. We fit different models of seeding from farms to two-strain surveillance data collected from Shantou, China. For a single strain and plausible estimates for continuous turnover rates and transmissibility, the CCS was approximately 11 800 birds, only a 4.2% increase in this estimate was needed to ensure persistence of the co-infecting strains (two strains in a single host). Precise values of CCS estimates were sensitive to changes in market turnover rate and duration of the latent period. Assuming a gradual daily sell rate of birds the estimated CCS was higher than when an instantaneous selling rate was assumed. We were able to reproduce prevalence dynamics similar to observations from a single market in China with infection seeded every 5–15 days, and a maximum non-seeding duration of 80 days. Our findings suggest that persistence of co-infections is more likely to be owing to sequential infection of single strains rather than ongoing transmission of both strains concurrently. In any given system for a fixed set of ecological and epidemiological conditions, there is an LBM size below which the risk of sustained co-circulation is low and which may suggest a clear policy opportunity to reduce the frequency of influenza co-infection in poultry.",2017 Dec 6,"['Pinsent, Amy', 'Pepin, Kim M.', 'Zhu, Huachen', 'Guan, Yi', 'White, Michael T.', 'Riley, Steven']",Proc Biol Sci,,,True
d0a5f35e229929f76c9c7fb1dcac16d5324c12e8,PMC,The persistence of multiple strains of avian influenza in live bird markets,http://dx.doi.org/10.1098/rspb.2017.0715,PMC5740266,29212718,CC BY,"Multiple subtypes of avian influenza (AI) and novel reassortants are frequently isolated from live bird markets (LBMs). However, our understanding of the drivers of persistence of multiple AI subtypes is limited. We propose a stochastic model of AI transmission within an LBM that incorporates market size, turnover rate and the balance of direct versus environmental transmissibility. We investigate the relationship between these factors and the critical community size (CCS) for the persistence of single and multiple AI strains within an LBM. We fit different models of seeding from farms to two-strain surveillance data collected from Shantou, China. For a single strain and plausible estimates for continuous turnover rates and transmissibility, the CCS was approximately 11 800 birds, only a 4.2% increase in this estimate was needed to ensure persistence of the co-infecting strains (two strains in a single host). Precise values of CCS estimates were sensitive to changes in market turnover rate and duration of the latent period. Assuming a gradual daily sell rate of birds the estimated CCS was higher than when an instantaneous selling rate was assumed. We were able to reproduce prevalence dynamics similar to observations from a single market in China with infection seeded every 5–15 days, and a maximum non-seeding duration of 80 days. Our findings suggest that persistence of co-infections is more likely to be owing to sequential infection of single strains rather than ongoing transmission of both strains concurrently. In any given system for a fixed set of ecological and epidemiological conditions, there is an LBM size below which the risk of sustained co-circulation is low and which may suggest a clear policy opportunity to reduce the frequency of influenza co-infection in poultry.",2017 Dec 6,"['Pinsent, Amy', 'Pepin, Kim M.', 'Zhu, Huachen', 'Guan, Yi', 'White, Michael T.', 'Riley, Steven']",Proc Biol Sci,,,True
a03517f26664be79239bcdf3dbb0966913206a86,PMC,Coronavirus and paramyxovirus in bats from Northwest Italy,http://dx.doi.org/10.1186/s12917-017-1307-x,PMC5741894,29273042,CC BY,"BACKGROUND: Bat-borne virus surveillance is necessary for determining inter-species transmission risks and is important due to the wide-range of bat species which may harbour potential pathogens. This study aimed to monitor coronaviruses (CoVs) and paramyxoviruses (PMVs) in bats roosting in northwest Italian regions. Our investigation was focused on CoVs and PMVs due to their proven ability to switch host and their zoonotic potential. Here we provide the phylogenetic characterization of the highly conserved polymerase gene fragments. RESULTS: Family-wide PCR screenings were used to test 302 bats belonging to 19 different bat species. Thirty-eight animals from 12 locations were confirmed as PCR positive, with an overall detection rate of 12.6% [95% CI: 9.3–16.8]. CoV RNA was found in 36 bats belonging to eight species, while PMV RNA in three Pipistrellus spp. Phylogenetic characterization have been obtained for 15 alpha- CoVs, 5 beta-CoVs and three PMVs; moreover one P. pipistrellus resulted co-infected with both CoV and PMV. A divergent alpha-CoV clade from Myotis nattereri SpA is also described. The compact cluster of beta-CoVs from R. ferrumequinum roosts expands the current viral sequence database, specifically for this species in Europe. To our knowledge this is the first report of CoVs in Plecotus auritus and M. oxygnathus, and of PMVs in P. kuhlii. CONCLUSIONS: This study identified alpha and beta-CoVs in new bat species and in previously unsurveyed Italian regions. To our knowledge this represents the first and unique report of PMVs in Italy. The 23 new bat genetic sequences presented will expand the current molecular bat-borne virus databases. Considering the amount of novel bat-borne PMVs associated with the emergence of zoonotic infections in animals and humans in the last years, the definition of viral diversity within European bat species is needed. Performing surveillance studies within a specific geographic area can provide awareness of viral burden where bats roost in close proximity to spillover hosts, and form the basis for the appropriate control measures against potential threats for public health and optimal management of bats and their habitats.",2017 Dec 22,"['Rizzo, Francesca', 'Edenborough, Kathryn M.', 'Toffoli, Roberto', 'Culasso, Paola', 'Zoppi, Simona', 'Dondo, Alessandro', 'Robetto, Serena', 'Rosati, Sergio', 'Lander, Angelika', 'Kurth, Andreas', 'Orusa, Riccardo', 'Bertolotti, Luigi', 'Mandola, Maria Lucia']",BMC Vet Res,,,True
ee0050c6fb81a4067d134010d0c80d21edb5df0b,PMC,Port d’Entrée for Respiratory Infections – Does the Influenza A Virus Pave the Way for Bacteria?,http://dx.doi.org/10.3389/fmicb.2017.02602,PMC5742597,29312268,CC BY,"Bacterial and viral co-infections of the respiratory tract are life-threatening and present a global burden to the global community. Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes are frequent colonizers of the upper respiratory tract. Imbalances through acquisition of seasonal viruses, e.g., Influenza A virus, can lead to bacterial dissemination to the lower respiratory tract, which in turn can result in severe pneumonia. In this review, we summarize the current knowledge about bacterial and viral co-infections of the respiratory tract and focus on potential experimental models suitable for mimicking this disease. Transmission of IAV and pneumonia is mainly modeled by mouse infection. Few studies utilizing ferrets, rats, guinea pigs, rabbits, and non-human primates are also available. The knowledge gained from these studies led to important discoveries and advances in understanding these infectious diseases. Nevertheless, mouse and other infection models have limitations, especially in translation of the discoveries to humans. Here, we suggest the use of human engineered lung tissue, human ex vivo lung tissue, and porcine models to study respiratory co-infections, which might contribute to a greater translation of the results to humans and improve both, animal and human health.",2017 Dec 21,"['Siemens, Nikolai', 'Oehmcke-Hecht, Sonja', 'Mettenleiter, Thomas C.', 'Kreikemeyer, Bernd', 'Valentin-Weigand, Peter', 'Hammerschmidt, Sven']",Front Microbiol,,,True
71afb4cf84163bef90c7ea2f8d816aef07582d85,PMC,Tracking the Origin and Deciphering the Phylogenetic Relationship of Porcine Epidemic Diarrhea Virus in Ecuador,http://dx.doi.org/10.1155/2017/2978718,PMC5742880,29379796,CC BY,"In 2010, new Chinese strains of porcine epidemic diarrhea virus (PEDV), clinically more severe than the classical strains, emerged. These strains were spread to United States in 2013 through an intercontinental transmission from China with further spreading across the world, evidencing the emergent nature of these strains. In the present study, an analysis of PEDV field sequences from Ecuador was conducted by comparing all the PEDV S gene sequences available in the GenBank database. Phylogenetic comparisons and Bayesian phylogeographic inference based on complete S gene sequences were also conducted to track the origin and putative route of PEDV. The sequence from the PED-outbreak in Ecuador was grouped into the clade II of PEDV genogroup 2a together with other sequences of isolates from Mexico, Canada, and United States. The phylogeographic study revealed the emergence of the Chinese PEDV strains, followed by spreading to US in 2013, from US to Korea, and later the introduction of PEDV to Canada, Mexico, and Ecuador directly from the US. The sources of imports of live swine in Ecuador in 2014 were mainly from Chile and US. Thus, this movement of pigs is suggested as the main way for introducing PEDV to Ecuador.",2017 Dec 12,"['Barrera, Maritza', 'Garrido-Haro, Ana', 'Vaca, María S.', 'Granda, Danilo', 'Acosta-Batallas, Alfredo', 'Pérez, Lester J.']",Biomed Res Int,,,True
c5157f9976942d166a600cb570a5a8fa9ab91e57,PMC,Quantitative Analysis of Cellular Proteome Alterations in CDV-Infected Mink Lung Epithelial Cells,http://dx.doi.org/10.3389/fmicb.2017.02564,PMC5743685,29312244,CC BY,"Canine distemper virus (CDV), a paramyxovirus, causes a severe highly contagious lethal disease in carnivores, such as mink. Mink lung epithelial cells (Mv.1.Lu cells) are sensitive to CDV infection and are homologous to the natural host system of mink. The current study analyzed the response of Mv.1.Lu cells to CDV infection by iTRAQ combined with LC–MS/MS. In total, 151 and 369 differentially expressed proteins (DEPs) were markedly up-regulated or down-regulated, respectively. Thirteen DEPs were validated via real-time RT-PCR or western blot analysis. Network and KEGG pathway analyses revealed several regulated proteins associated with the NF-κB signaling pathway. Further validation was performed by western blot analysis and immunofluorescence assay, which demonstrated that different CDV strains induced NF-κB P65 phosphorylation and nuclear translocation. Moreover, the results provided interesting information that some identified DEPs possibly associated with the pathogenesis and the immune response upon CDV infection. This study is the first overview of the responses to CDV infection in Mv.1.Lu cells, and the findings will help to analyze further aspects of the molecular mechanisms involved in viral pathogenesis and the immune responses upon CDV infection.",2017 Dec 22,"['Tong, Mingwei', 'Yi, Li', 'Sun, Na', 'Cheng, Yuening', 'Cao, Zhigang', 'Wang, Jianke', 'Li, Shuang', 'Lin, Peng', 'Sun, Yaru', 'Cheng, Shipeng']",Front Microbiol,,,True
8c34e09a2de5c62460eaf9258b999db404719dcb,PMC,Dietary Probiotic Compound Improves Reproductive Performance of Porcine Epidemic Diarrhea Virus-Infected Sows Reared in a Japanese Commercial Swine Farm under Vaccine Control Condition,http://dx.doi.org/10.3389/fimmu.2017.01877,PMC5743915,29312349,CC BY,"Lactogenic immunity transferred to piglets after inoculation of a live vaccine to pregnant sows was proved limited to control porcine epidemic diarrhea (PED). Hence, here we evaluated the efficacy of administration of a probiotic compound containing Bacillus mesentericus, Clostridium butyricum, and Enterococcus faecalis together with a commercial live-attenuated PED vaccine (Nisseiken PED Live Vaccine, Nisseiken, Tokyo, Japan) to improve the health and reproductive performance of PED-infected sows. Twenty pregnant sows in a PED-positive farm were equally divided into probiotics-administered (VP) and control (VC) sow groups. A commercial live-attenuated vaccine was injected as per the manufacturer’s instruction. The probiotic compound (15 g/day) was orally administered to VP from 6 weeks pre-parturition to 7 days post-parturition (ppd7). VP had a significantly higher body weight at ppd7 than VC (191 vs 186 kg; P < 0.05). At day 3 post-parturition (ppd3) (4.18 vs 3.63 kg/day) and ppd7 (5.14 vs 4.34 kg/day), milk produced by VP was significantly (P < 0.05) greater than that by VC. Total immunoglobulin (Ig)A and IgG concentrations at day 0 were significantly (P < 0.05) higher in whey of VP (1.9 and 6.6 g/dL, respectively) than in that of VC (1.7 and 6.1 g/dL, respectively). However, total IgG concentration in whey of VP and VC at ppd3 and ppd7 did not differ. Antibody titer was significantly higher at day 0 in serum of VP than it was that of VC (60 vs 37 in geometric mean; P < 0.05). Likewise, the antibody titer in whey of VP and VC was found to be similar at day 0 (416 vs 208 in geometric mean; P = 0.13). Consequently, VP had fewer days between weaning and return to estrus than did VC (7 vs 10 days; P < 0.05). Moreover, piglets of VP had a significantly (P < 0.05) higher litter weight at birth (9,252 g/litter) and a lower mortality (12%) during suckling than those of VC (8,686 g/litter and 28%, respectively). In summary, probiotic-supplemented, PED-vaccinated sows were healthier, transferred PED-specific antibodies via colostrum to piglets, had greater litter weight at birth, and reduced mortality during suckling.",2017 Dec 22,"['Inatomi, Takio', 'Amatatsu, Masaaki', 'Romero-Pérez, Gustavo A.', 'Inoue, Ryo', 'Tsukahara, Takamitsu']",Front Immunol,,,True
a21bbf97490642e6230c9c6eeece5cb99447b566,PMC,"Identification of Alpha and Beta Coronavirus in Wildlife Species in France: Bats, Rodents, Rabbits, and Hedgehogs",http://dx.doi.org/10.3390/v9120364,PMC5744139,29186061,CC BY,"Coronaviruses are closely monitored in the context of emerging diseases and, as illustrated with Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome-coronavirus (MERS-CoV), are known to cross the species barrier and eventually to move from wildlife to humans. Knowledge of the diversity of coronaviruses in wildlife is therefore essential to better understand and prevent emergence events. This study explored the presence of coronaviruses in four wild mammal orders in France: Bats, rodents, lagomorphs, and hedgehogs. Betacoronavirus and Alphacoronavirus genera were identified. The results obtained suggest the circulation of potentially evolving virus strains, with the potential to cross the species barrier.",2017 Nov 29,"['Monchatre-Leroy, Elodie', 'Boué, Franck', 'Boucher, Jean-Marc', 'Renault, Camille', 'Moutou, François', 'Ar Gouilh, Meriadeg', 'Umhang, Gérald']",Viruses,,,True
19eed2e91c17ea20e9cbda665e19fad13a948ecf,PMC,Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response,http://dx.doi.org/10.3390/v9120365,PMC5744140,29194430,CC BY,"Cellular receptor-mediated signaling pathways play critical roles during the initial immune response to Human Cytomegalovirus (HCMV) infection. However, the involvement of type-I transmembrane glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) in the antiviral response to HCMV infection is still unknown. Here, we demonstrated the specific knockdown of CD147 significantly decreased HCMV-induced activation of NF-κB and Interferon-beta (IFN-β), which contribute to the cellular antiviral responses. Next, we confirmed that HCMV-encoded miR-US25-1-5p could target the 3′ UTR (Untranslated Region) of CD147 mRNA, and thus facilitate HCMV lytic propagation at a low multiplicity of infection (MOI). The expression and secretion of Cyclophilin A (sCyPA), as a ligand for CD147 and a proinflammatory cytokine, were up-regulated in response to HCMV stimuli. Finally, we confirmed that CD147 mediated HCMV-triggered antiviral signaling via the sCyPA-CD147-ERK (extracellular regulated protein kinases)/NF-κB axis signaling pathway. These findings reveal an important HCMV mechanism for evading antiviral innate immunity through its encoded microRNA by targeting transmembrane glycoprotein CD147, and a potential cause of HCMV inflammatory disorders due to the secretion of proinflammatory cytokine CyPA.",2017 Dec 1,"['Chen, Jun', 'Xia, Sisi', 'Yang, Xiangmin', 'Chen, Huizi', 'Li, Fanni', 'Liu, Fenyong', 'Chen, Zhinan']",Viruses,,,True
32da24606ad160166f08cf05349eaadd580ccff0,PMC,An Opportunistic Pathogen Afforded Ample Opportunities: Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.3390/v9120369,PMC5744144,29207494,CC BY,"The human coronaviruses (CoV) include HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, some of which have been known for decades. The severe acute respiratory syndrome (SARS) CoV briefly emerged into the human population but was controlled. In 2012, another novel severely human pathogenic CoV—the Middle East Respiratory Syndrome (MERS)-CoV—was identified in the Kingdom of Saudi Arabia; 80% of over 2000 human cases have been recorded over five years. Targeted research remains key to developing control strategies for MERS-CoV, a cause of mild illness in its camel reservoir. A new therapeutic toolbox being developed in response to MERS is also teaching us more about how CoVs cause disease. Travel-related cases continue to challenge the world’s surveillance and response capabilities, and more data are needed to understand unexplained primary transmission. Signs of genetic change have been recorded, but it remains unclear whether there is any impact on clinical disease. How camels came to carry the virus remains academic to the control of MERS. To date, human-to-human transmission has been inefficient, but virus surveillance, characterisation, and reporting are key to responding to any future change. MERS-CoV is not currently a pandemic threat; it is spread mainly with the aid of human habit and error.",2017 Dec 2,"['Mackay, Ian M.', 'Arden, Katherine E.']",Viruses,,,True
26f219a1d536118b973f8948cd564b53beb649fe,PMC,Subcellular Trafficking of the Papillomavirus Genome during Initial Infection: The Remarkable Abilities of Minor Capsid Protein L2,http://dx.doi.org/10.3390/v9120370,PMC5744145,29207511,CC BY,"Since 2012, our understanding of human papillomavirus (HPV) subcellular trafficking has undergone a drastic paradigm shift. Work from multiple laboratories has revealed that HPV has evolved a unique means to deliver its viral genome (vDNA) to the cell nucleus, relying on myriad host cell proteins and processes. The major breakthrough finding from these recent endeavors has been the realization of L2-dependent utilization of cellular sorting factors for the retrograde transport of vDNA away from degradative endo/lysosomal compartments to the Golgi, prior to mitosis-dependent nuclear accumulation of L2/vDNA. An overview of current models of HPV entry, subcellular trafficking, and the role of L2 during initial infection is provided below, highlighting unresolved questions and gaps in knowledge.",2017 Dec 3,"Campos, Samuel K.",Viruses,,,True
ba2d0f6467116c99ad6bc4df52b616cc683aecb5,PMC,The impact of persistent bacterial bronchitis on the pulmonary microbiome of children,http://dx.doi.org/10.1371/journal.pone.0190075,PMC5744971,29281698,CC BY,"INTRODUCTION: Persistent bacterial bronchitis (PBB) is a leading cause of chronic wet cough in young children. This study aimed to characterise the respiratory bacterial microbiota of healthy children and to assess the impact of the changes associated with the development of PBB. Blind, protected brushings were obtained from 20 healthy controls and 24 children with PBB, with an additional directed sample obtained from PBB patients. DNA was extracted, quantified using a 16S rRNA gene quantitative PCR assay prior to microbial community analysis by 16S rRNA gene sequencing. RESULTS: No significant difference in bacterial diversity or community composition (R(2) = 0.01, P = 0.36) was observed between paired blind and non-blind brushes, showing that blind brushings are a valid means of accessing the airway microbiota. This has important implications for collecting lower respiratory samples from healthy children. A significant decrease in bacterial diversity (P < 0.001) and change in community composition (R(2) = 0.08, P = 0.004) was observed among controls, in comparison with patients. Bacterial communities within patients with PBB were dominated by Proteobacteria, and indicator species analysis showed that Haemophilus and Neisseria were significantly associated with the patient group. In 15 (52.9%) cases the dominant organism by sequencing was not identified by standard routine clinical culture. CONCLUSION: The bacteria present in the lungs of patients with PBB were less diverse in terms of richness and evenness. The results validate the clinical diagnosis, and suggest that more attention to bacterial communities in children with chronic cough may lead to more rapid recognition of this condition with earlier treatment and reduction in disease burden.",2017 Dec 27,"['Cuthbertson, Leah', 'Craven, Vanessa', 'Bingle, Lynne', 'Cookson, William O. C. M.', 'Everard, Mark L.', 'Moffatt, Miriam F.']",PLoS One,,,True
d8af816aad9d7cfe8c158cefaa7f1de16bda7146,PMC,"Rabies elimination research: juxtaposing optimism, pragmatism and realism",http://dx.doi.org/10.1098/rspb.2017.1880,PMC5745407,29263285,CC BY,"More than 100 years of research has now been conducted into the prevention, control and elimination of rabies with safe and highly efficacious vaccines developed for use in human and animal populations. Domestic dogs are a major reservoir for rabies, and although considerable advances have been made towards the elimination and control of canine rabies in many parts of the world, the disease continues to kill tens of thousands of people every year in Africa and Asia. Policy efforts are now being directed towards a global target of zero human deaths from dog-mediated rabies by 2030 and the global elimination of canine rabies. Here we demonstrate how research provides a cause for optimism as to the feasibility of these goals through strategies based around mass dog vaccination. We summarize some of the pragmatic insights generated from rabies epidemiology and dog ecology research that can improve the design of dog vaccination strategies in low- and middle-income countries and which should encourage implementation without further delay. We also highlight the need for realism in reaching the feasible, although technically more difficult and longer-term goal of global elimination of canine rabies. Finally, we discuss how research on rabies has broader relevance to the control and elimination of a suite of diseases of current concern to human and animal health, providing an exemplar of the value of a ‘One Health’ approach.",2017 Dec 20,"['Cleaveland, Sarah', 'Hampson, Katie']",Proc Biol Sci,,,True
bd108a54d3d8e9f2a2389a2ee26798259273fd3b,PMC,The evolving role of the renin–angiotensin system in ARDS,http://dx.doi.org/10.1186/s13054-017-1917-5,PMC5746002,29284527,CC BY,,2017 Dec 28,"['Vrigkou, Eleni', 'Tsangaris, Iraklis', 'Bonovas, Stefanos', 'Tsantes, Argyrios', 'Kopterides, Petros']",Crit Care,,,True
627ada5c21fb8d0e43b37999fa66bf41ca36c353,PMC,Analysis of the codon usage pattern in Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.18632/oncotarget.22738,PMC5746386,29299151,CC BY,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which first broken out in Jeddah in 2012, causes a severe acute respiratory illness with a high mortality rate. To better understand the molecular characteristics of isolated MERS-CoV genomes, we first analysed the codon usage pattern of the zoonotic MERS-CoV strains comprehensively to gain an insight into the mechanism of cross-species transmission. We found that MERS human/camel isolates showed a low codon usage bias. Both mutation and nature selection pressure have contributed to this low codon usage bias, with the former being the main determining factor. We also observed that gene function, evolution time and the different host species of the virus all contributed to the bias of MERS-CoV, to some extent. Additionally, the codon usage pattern of MERS-CoV isolates is different from other related Nidovirales viruses isolated from bats and hedgehogs. In the future, more epidemiological surveys are required to examine the factors that resulted in the emergence and outbreak of this virus.",2017 Nov 27,"['Chen, Ye', 'Xu, Quanming', 'Yuan, Xiaomin', 'Li, Xinxin', 'Zhu, Ting', 'Ma, Yanmei', 'Chen, Ji-Long']",Oncotarget,,,True
25481ba834557c4417f674b0db5b627af1ab6ad9,PMC,Analysis of the codon usage pattern in Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.18632/oncotarget.22738,PMC5746386,29299151,CC BY,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which first broken out in Jeddah in 2012, causes a severe acute respiratory illness with a high mortality rate. To better understand the molecular characteristics of isolated MERS-CoV genomes, we first analysed the codon usage pattern of the zoonotic MERS-CoV strains comprehensively to gain an insight into the mechanism of cross-species transmission. We found that MERS human/camel isolates showed a low codon usage bias. Both mutation and nature selection pressure have contributed to this low codon usage bias, with the former being the main determining factor. We also observed that gene function, evolution time and the different host species of the virus all contributed to the bias of MERS-CoV, to some extent. Additionally, the codon usage pattern of MERS-CoV isolates is different from other related Nidovirales viruses isolated from bats and hedgehogs. In the future, more epidemiological surveys are required to examine the factors that resulted in the emergence and outbreak of this virus.",2017 Nov 27,"['Chen, Ye', 'Xu, Quanming', 'Yuan, Xiaomin', 'Li, Xinxin', 'Zhu, Ting', 'Ma, Yanmei', 'Chen, Ji-Long']",Oncotarget,,,False
3c7a2bc73e390cf72261519f241cd12b363c7444,PMC,Strategies Using Bio-Layer Interferometry Biosensor Technology for Vaccine Research and Development,http://dx.doi.org/10.3390/bios7040049,PMC5746772,29088096,CC BY,"Bio-layer interferometry (BLI) real-time, label-free technology has greatly contributed to advances in vaccine research and development. BLI Octet platforms offer high-throughput, ease of use, reliability, and high precision analysis when compared with common labeling techniques. Many different strategies have been used to immobilize the pathogen or host molecules on BLI biosensors for real-time kinetics and affinity analysis, quantification, or high-throughput titer. These strategies can be used in multiple applications and shed light onto the structural and functional aspects molecules play during pathogen-host interactions. They also provide crucial information on how to achieve protection. This review summarizes some key BLI strategies used in human vaccine research and development.",2017 Oct 31,"Petersen, Rejane L.",Biosensors (Basel),,,True
e5146a4b1c9ae4171d885efabc99ff1cc997aeec,PMC,Predicted protein interactions of IFITMs may shed light on mechanisms of Zika virus-induced microcephaly and host invasion,http://dx.doi.org/10.12688/f1000research.9364.2,PMC5747333,29333229,CC BY,"After the first reported case of Zika virus (ZIKV) in Brazil, in 2015, a significant increase in the reported cases of microcephaly was observed. Microcephaly is a neurological condition in which the infant’s head is significantly smaller with complications in brain development. Recently, two small membrane-associated interferon-inducible transmembrane proteins (IFITM1 and IFITM3) have been shown to repress members of the flaviviridae family which includes ZIKV. However, the exact mechanisms leading to the inhibition of the virus are yet unknown. Here, we assembled an interactome of IFITM1 and IFITM3 with known protein-protein interactions (PPIs) collected from publicly available databases and novel PPIs predicted using the High-confidence Protein-Protein Interaction Prediction (HiPPIP) model. We analyzed the functional and pathway associations of the interacting proteins, and found that there are several immunity pathways (toll-like receptor signaling, cd28 signaling in T-helper cells, crosstalk between dendritic cells and natural killer cells), neuronal pathways (axonal guidance signaling, neural tube closure and actin cytoskeleton signaling) and developmental pathways (neural tube closure, embryonic skeletal system development) that are associated with these interactors. Our novel PPIs associate cilia dysfunction in ependymal cells to microcephaly, and may also shed light on potential targets of ZIKV for host invasion by immunosuppression and cytoskeletal rearrangements. These results could help direct future research in elucidating the mechanisms underlying host defense to ZIKV and other flaviviruses.",2017 Nov 21,"['Ganapathiraju, Madhavi K.', 'Karunakaran, Kalyani B.', 'Correa-Menéndez, Josefina']",F1000Res,,,True
607d648e224430e7c79b94f6c2d770272616c5bc,PMC,"A diagnostic and epidemiologic investigation of acute febrile illness (AFI) in Kilombero, Tanzania",http://dx.doi.org/10.1371/journal.pone.0189712,PMC5747442,29287070,CC0,"INTRODUCTION: In low-resource settings, empiric case management of febrile illness is routine as a result of limited access to laboratory diagnostics. The use of comprehensive fever syndromic surveillance, with enhanced clinical microbiology, advanced diagnostics and more robust epidemiologic investigation, could enable healthcare providers to offer a differential diagnosis of fever syndrome and more appropriate care and treatment. METHODS: We conducted a year-long exploratory study of fever syndrome among patients ≥ 1 year if age, presenting to clinical settings with an axillary temperature of ≥37.5°C and symptomatic onset of ≤5 days. Blood and naso-pharyngeal/oral-pharyngeal (NP/OP) specimens were collected and analyzed, respectively, using AFI and respiratory TaqMan Array Cards (TAC) for multi-pathogen detection of 57 potential causative agents. Furthermore, we examined numerous epidemiologic correlates of febrile illness, and conducted demographic, clinical, and behavioral domain-specific multivariate regression to statistically establish associations with agent detection. RESULTS: From 15 September 2014–13 September 2015, 1007 febrile patients were enrolled, and 997 contributed an epidemiologic survey, including: 14% (n = 139) 1<5yrs, 19% (n = 186) 5-14yrs, and 67% (n = 672) ≥15yrs. AFI TAC and respiratory TAC were performed on 842 whole blood specimens and 385 NP/OP specimens, respectively. Of the 57 agents surveyed, Plasmodium was the most common agent detected. AFI TAC detected nucleic acid for one or more of seven microbial agents in 49% of AFI blood samples, including: Plasmodium (47%), Leptospira (3%), Bartonella (1%), Salmonella enterica (1%), Coxiella burnetii (1%), Rickettsia (1%), and West Nile virus (1%). Respiratory TAC detected nucleic acid for 24 different microbial agents, including 12 viruses and 12 bacteria. The most common agents detected among our surveyed population were: Haemophilus influenzae (67%), Streptococcus pneumoniae (55%), Moraxella catarrhalis (39%), Staphylococcus aureus (37%), Pseudomonas aeruginosa (36%), Human Rhinovirus (25%), influenza A (24%), Klebsiella pneumoniae (14%), Enterovirus (15%) and group A Streptococcus (12%). Our epidemiologic investigation demonstrated both age and symptomatic presentation to be associated with a number of detected agents, including, but not limited to, influenza A and Plasmodium. Linear regression of fully-adjusted mean cycle threshold (C(t)) values for Plasmodium also identified statistically significant lower mean C(t) values for older children (20.8), patients presenting with severe fever (21.1) and headache (21.5), as well as patients admitted for in-patient care and treatment (22.4). CONCLUSIONS: This study is the first to employ two syndromic TaqMan Array Cards for the simultaneous survey of 57 different organisms to better characterize the type and prevalence of detected agents among febrile patients. Additionally, we provide an analysis of the association between adjusted mean C(t) values for Plasmodium and key clinical and demographic variables, which may further inform clinical decision-making based upon intensity of infection, as observed across endemic settings of sub-Saharan Africa.",2017 Dec 29,"['Hercik, Christine', 'Cosmas, Leonard', 'Mogeni, Ondari D.', 'Wamola, Newton', 'Kohi, Wanze', 'Omballa, Victor', 'Ochieng, Melvin', 'Lidechi, Shirley', 'Bonventure, Juma', 'Ochieng, Caroline', 'Onyango, Clayton', 'Fields, Barry S.', 'Mfinanga, Sayoki', 'Montgomery, Joel M.']",PLoS One,,,True
4f7c1aeb6e5b1e35d6be98d478259a83a8dd6993,PMC,"Epidemiology of Respiratory Pathogens among Elderly Nursing Home Residents with Acute Respiratory Infections in Corsica, France, 2013–2017",http://dx.doi.org/10.1155/2017/1423718,PMC5748090,29392127,CC BY,"BACKGROUND: The current study aims to describe the demographical and clinical characteristics of elderly nursing home (NH) residents with acute respiratory infections (ARIs) during four winter seasons (2013/2014–2016/2017), as well as the microbiological etiology of these infections. METHODS: Seventeen NHs with at least one ARI resident in Corsica, France, were included. An ARI resident was defined as a resident developing a sudden onset of any constitutional symptoms in addition to any respiratory signs. Nasopharyngeal swabs from ARI residents were screened for the presence of 21 respiratory agents, including seasonal influenza viruses. RESULTS: Of the 107 ARI residents enrolled from NHs, 61 (57%) were positive for at least one of the 21 respiratory pathogens. Forty-one (38.3%) of the 107 ARI residents had influenza: 38 (92%) were positive for influenza A (100% A(H3N2)) and three (8%) for influenza B/Victoria. Axillary fever (≥38°C) was significantly more common among patients infected with influenza A(H3N2). CONCLUSION: The circulation of seasonal respiratory viruses other than influenza A(H3N2) seems to be sporadic among elderly NH residents. Investigating the circulation of respiratory viruses in nonwinter seasons seems to be important in order to understand better the dynamic of their year-round circulation in NHs.",2017 Dec 17,"['Masse, Shirley', 'Capai, Lisandru', 'Falchi, Alessandra']",Biomed Res Int,,,True
27ee6e389b8f87a3545232db8b8fe385f73e5003,PMC,Elucidating the Role of Host Long Non-Coding RNA during Viral Infection: Challenges and Paths Forward,http://dx.doi.org/10.3390/vaccines5040037,PMC5748604,29053596,CC BY,"Research over the past decade has clearly shown that long non-coding RNAs (lncRNAs) are functional. Many lncRNAs can be related to immunity and the host response to viral infection, but their specific functions remain largely elusive. The vast majority of lncRNAs are annotated with extremely limited knowledge and tend to be expressed at low levels, making ad hoc experimentation difficult. Changes to lncRNA expression during infection can be systematically profiled using deep sequencing; however, this often produces an intractable number of candidate lncRNAs, leaving no clear path forward. For these reasons, it is especially important to prioritize lncRNAs into high-confidence “hits” by utilizing multiple methodologies. Large scale perturbation studies may be used to screen lncRNAs involved in phenotypes of interest, such as resistance to viral infection. Single cell transcriptome sequencing quantifies cell-type specific lncRNAs that are less abundant in a mixture. When coupled with iterative experimental validations, new computational strategies for efficiently integrating orthogonal high-throughput data will likely be the driver for elucidating the functional role of lncRNAs during viral infection. This review highlights new high-throughput technologies and discusses the potential for integrative computational analysis to streamline the identification of infection-related lncRNAs and unveil novel targets for antiviral therapeutics.",2017 Oct 20,"['Lemler, David J.', 'Brochu, Hayden N.', 'Yang, Fang', 'Harrell, Erin A.', 'Peng, Xinxia']",Vaccines (Basel),,,True
b5464879315d206d3053d3cfbba9b3d914e8b709,PMC,Detection of Nuclear Protein Profile Changes by Human Metapneumovirus M2-2 Protein Using Quantitative Differential Proteomics,http://dx.doi.org/10.3390/vaccines5040045,PMC5748611,29207503,CC BY,"Human metapneumovirus (hMPV) is a leading cause of lower respiratory infection in pediatric populations globally. This study examined proteomic profile changes in A549 cells infected with hMPV and two attenuated mutants with deleted PDZ domain-binding motif(s) in the M2-2 protein. These motifs are involved in the interruption of antiviral signaling, namely the interaction between the TNF receptor associated factor (TRAF) and mitochondrial antiviral-signaling (MAVS) proteins. The aim of this study was to provide insight into the overall and novel impact of M2-2 motifs on cellular responses via an unbiased comparison. Tandem mass tagging, stable isotope labeling, and high-resolution mass spectrometry were used for quantitative proteomic analysis. Using quantitative proteomics and Venn analysis, 1248 common proteins were detected in all infected samples of both technical sets. Hierarchical clustering of the differentiated proteome displayed distinct proteomic signatures that were controlled by the motif(s). Bioinformatics and experimental analysis confirmed the differentiated proteomes, revealed novel cellular biological events, and implicated key pathways controlled by hMPV M2-2 PDZ domain-binding motif(s). This provides further insight for evaluating M2-2 mutants as potent vaccine candidates.",2017 Dec 3,"['Ren, Yuping', 'Choi, Eunjin', 'Zhang, Ke', 'Chen, Yu', 'Ye, Sha', 'Deng, Xiaoling', 'Zhang, Kangling', 'Bao, Xiaoyong']",Vaccines (Basel),,,True
c2bd145cf6cbd380dc5fa1272dfadd18e0262382,PMC,Detection of Nuclear Protein Profile Changes by Human Metapneumovirus M2-2 Protein Using Quantitative Differential Proteomics,http://dx.doi.org/10.3390/vaccines5040045,PMC5748611,29207503,CC BY,"Human metapneumovirus (hMPV) is a leading cause of lower respiratory infection in pediatric populations globally. This study examined proteomic profile changes in A549 cells infected with hMPV and two attenuated mutants with deleted PDZ domain-binding motif(s) in the M2-2 protein. These motifs are involved in the interruption of antiviral signaling, namely the interaction between the TNF receptor associated factor (TRAF) and mitochondrial antiviral-signaling (MAVS) proteins. The aim of this study was to provide insight into the overall and novel impact of M2-2 motifs on cellular responses via an unbiased comparison. Tandem mass tagging, stable isotope labeling, and high-resolution mass spectrometry were used for quantitative proteomic analysis. Using quantitative proteomics and Venn analysis, 1248 common proteins were detected in all infected samples of both technical sets. Hierarchical clustering of the differentiated proteome displayed distinct proteomic signatures that were controlled by the motif(s). Bioinformatics and experimental analysis confirmed the differentiated proteomes, revealed novel cellular biological events, and implicated key pathways controlled by hMPV M2-2 PDZ domain-binding motif(s). This provides further insight for evaluating M2-2 mutants as potent vaccine candidates.",2017 Dec 3,"['Ren, Yuping', 'Choi, Eunjin', 'Zhang, Ke', 'Chen, Yu', 'Ye, Sha', 'Deng, Xiaoling', 'Zhang, Kangling', 'Bao, Xiaoyong']",Vaccines (Basel),,,False
fb077b4ea64b29cf81d88b9160f6ebb1d4a3d776,PMC,Current Research on Non-Coding Ribonucleic Acid (RNA),http://dx.doi.org/10.3390/genes8120366,PMC5748684,29206165,CC BY,"Non-coding ribonucleic acid (RNA) has without a doubt captured the interest of biomedical researchers. The ability to screen the entire human genome with high-throughput sequencing technology has greatly enhanced the identification, annotation and prediction of the functionality of non-coding RNAs. In this review, we discuss the current landscape of non-coding RNA research and quantitative analysis. Non-coding RNA will be categorized into two major groups by size: long non-coding RNAs and small RNAs. In long non-coding RNA, we discuss regular long non-coding RNA, pseudogenes and circular RNA. In small RNA, we discuss miRNA, transfer RNA, piwi-interacting RNA, small nucleolar RNA, small nuclear RNA, Y RNA, single recognition particle RNA, and 7SK RNA. We elaborate on the origin, detection method, and potential association with disease, putative functional mechanisms, and public resources for these non-coding RNAs. We aim to provide readers with a complete overview of non-coding RNAs and incite additional interest in non-coding RNA research.",2017 Dec 5,"['Wang, Jing', 'Samuels, David C.', 'Zhao, Shilin', 'Xiang, Yu', 'Zhao, Ying-Yong', 'Guo, Yan']",Genes (Basel),,,True
9a5586078edf5a43100db04f987d635d39fee4a5,PMC,A 2-year follow-up study of patients with pharyngotonsillitis,http://dx.doi.org/10.1186/s12879-017-2917-4,PMC5749013,29291704,CC BY,"BACKGROUND: Longtime follow-up studies on patients with pharyngotonsillitis are rare. We aimed to describe the patterns of new visits for a sore throat, complications and tonsillectomy during 2 years in a cohort of patients with pharyngotonsillitis and non-infected controls. METHODS: A retrospective chart review was performed on a cohort of patients with acute sore throat (n = 207), and non-infected controls (n = 108). New visits, complications and tonsillectomy within 2 years was recorded and analyzed in relation to microbiological findings at inclusion. RESULTS: Patients with Group A streptococci (GAS) (12/66) reconsulted more often within 30 days than patients with no GAS (9/141) (p = 0.009) and patients with F. necrophorum (2/29). After 2 years, we observed no significant differences in reconsultations with regard to aetiology at inclusion. A single complication was recorded and 5 patients were planned for tonsillectomy. CONCLUSIONS: Group A streptococci were the sole aetiological agent associated with recurrent sore throat while F. necrophorum did not distinguish itself as a major cause of either recurrent infection or complications in this cohort. More studies, preferably with the focus on adolescents, are needed before F. necrophorum can be considered an important cause of pharyngotonsillitis.",2018 Jan 2,"['Pallon, Jon', 'Sundqvist, Martin', 'Hedin, Katarina']",BMC Infect Dis,,,True
8f3221b42c66b835706134994f7b71f10f9b104d,PMC,"Cage size, movement in and out of housing during daily care, and other environmental and population health risk factors for feline upper respiratory disease in nine North American animal shelters",http://dx.doi.org/10.1371/journal.pone.0190140,PMC5749746,29293542,CC BY,"Upper respiratory infection (URI) is not an inevitable consequence of sheltering homeless cats. This study documents variation in risk of URI between nine North American shelters; determines whether this reflects variation in pathogen frequency on intake or differences in transmission and expression of disease; and identifies modifiable environmental and group health factors linked to risk for URI. This study demonstrated that although periodic introduction of pathogens into shelter populations may be inevitable, disease resulting from those pathogens is not. Housing and care of cats, particularly during their first week of stay in an animal shelter environment, significantly affects the rate of upper respiratory infection.",2018 Jan 2,"['Wagner, Denae C.', 'Kass, Philip H.', 'Hurley, Kate F.']",PLoS One,,,True
e5fe8631b7f7e99f1e71c0cffc582d135c7181a2,PMC,Probing the antigenicity of hepatitis C virus envelope glycoprotein complex by high-throughput mutagenesis,http://dx.doi.org/10.1371/journal.ppat.1006735,PMC5749897,29253863,CC BY,"The hepatitis C virus (HCV) envelope glycoproteins E1 and E2 form a non-covalently linked heterodimer on the viral surface that mediates viral entry. E1, E2 and the heterodimer complex E1E2 are candidate vaccine antigens, but are technically challenging to study because of difficulties in producing natively folded proteins by standard protein expression and purification methods. To better comprehend the antigenicity of these proteins, a library of alanine scanning mutants comprising the entirety of E1E2 (555 residues) was created for evaluating the role of each residue in the glycoproteins. The mutant library was probed, by a high-throughput flow cytometry-based assay, for binding with the co-receptor CD81, and a panel of 13 human and mouse monoclonal antibodies (mAbs) that target continuous and discontinuous epitopes of E1, E2, and the E1E2 complex. Together with the recently determined crystal structure of E2 core domain (E2c), we found that several residues in the E2 back layer region indirectly impact binding of CD81 and mAbs that target the conserved neutralizing face of E2. These findings highlight an unexpected role for the E2 back layer in interacting with the E2 front layer for its biological function. We also identified regions of E1 and E2 that likely located at or near the interface of the E1E2 complex, and determined that the E2 back layer also plays an important role in E1E2 complex formation. The conformation-dependent reactivity of CD81 and the antibody panel to the E1E2 mutant library provides a global view of the influence of each amino acid (aa) on E1E2 expression and folding. This information is valuable for guiding protein engineering efforts to enhance the antigenic properties and stability of E1E2 for vaccine antigen development and structural studies.",2017 Dec 18,"['Gopal, Radhika', 'Jackson, Kelli', 'Tzarum, Netanel', 'Kong, Leopold', 'Ettenger, Andrew', 'Guest, Johnathan', 'Pfaff, Jennifer M.', 'Barnes, Trevor', 'Honda, Andrew', 'Giang, Erick', 'Davidson, Edgar', 'Wilson, Ian A.', 'Doranz, Benjamin J.', 'Law, Mansun']",PLoS Pathog,,,True
1340cfab5e9d9c4e29144766f379fe8f10e4cc29,PMC,Improving Virus Taxonomy by Recontextualizing Sequence-Based Classification with Biologically Relevant Data: the Case of the Alphacoronavirus 1 Species,http://dx.doi.org/10.1128/mSphereDirect.00463-17,PMC5750389,29299531,CC BY,"The difficulties related to virus taxonomy have been amplified by recent advances in next-generation sequencing and metagenomics, prompting the field to revisit the question of what constitutes a useful viral classification. Here, taking a challenging classification found in coronaviruses, we argue that consideration of biological properties in addition to sequence-based demarcations is critical for generating useful taxonomy that recapitulates complex evolutionary histories. Within the Alphacoronavirus genus, the Alphacoronavirus 1 species encompasses several biologically distinct viruses. We carried out functionally based phylogenetic analysis, centered on the spike gene, which encodes the main surface antigen and primary driver of tropism and pathogenesis. Within the Alphacoronavirus 1 species, we identify clade A (encompassing serotype I feline coronavirus [FCoV] and canine coronavirus [CCoV]) and clade B (grouping serotype II FCoV and CCoV and transmissible gastroenteritis virus [TGEV]-like viruses). We propose this clade designation, along with the newly proposed Alphacoronavirus 2 species, as an improved way to classify the Alphacoronavirus genus. IMPORTANCE Our work focuses on improving the classification of the Alphacoronavirus genus. The Alphacoronavirus 1 species groups viruses of veterinary importance that infect distinct mammalian hosts and includes canine and feline coronaviruses and transmissible gastroenteritis virus. It is the prototype species of the Alphacoronavirus genus; however, it encompasses biologically distinct viruses. To better characterize this prototypical species, we performed phylogenetic analyses based on the sequences of the spike protein, one of the main determinants of tropism and pathogenesis, and reveal the existence of two subgroups or clades that fit with previously established serotype demarcations. We propose a new clade designation to better classify Alphacoronavirus 1 members.",2018 Jan 3,"['Whittaker, Gary R.', 'André, Nicole M.', 'Millet, Jean Kaoru']",mSphere,,,True
db7abfe9ffd34b558951907efa3be430d7bbf28b,PMC,"Incidence of anogenital warts in Liuzhou, south China: a comparison of data from a prospective study and from the national surveillance system",http://dx.doi.org/10.1038/emi.2017.100,PMC5750456,29259326,CC BY,"To determine the incidence of anogenital warts (AGWs) in the Chinese general population, we compared the data from a prospective study and from the National Notifiable Disease Report System (NNDRS). A cohort study including 2378 women and 2309 men aged 18–55 years old enrolled from Liuzhou, China, was conducted with three scheduled visits at 6-month intervals from May 2014 to March 2016. And, a questionnaire survey was performed to collect the diagnosis history of AGWs at the enrollment visit. The data on reported AGW cases of Liuzhou in the NNDRS from 2006 to 2015 were also analyzed. Overall, the incidence rates of AGWs in the prospective study, in the self-reported diagnosis during past 12 months and in the NNDRS were 1.26 per 1000 person-years (95% confidence interval (CI): 0.16–2.37), 2.35 (95% CI: 1.17–4.20) and 0.183 (95% CI: 0.178–0.187), respectively. Human papillomavirus 6 or 11 were found in all the AGW biopsy samples (10/10). The onset time of AGWs in women was earlier, and the cumulative risk increased more quickly at a young age along with each subsequent younger birth cohort (P<0.0001), whereas slight differences were observed in the different male birth cohorts (P=0.0785). The sexual behavior of individuals and their sexual partners had a strong relationship with self-reported AGWs. Our study indicates that the incidence of AGWs in China is as high as that in developed countries, and the data based on the national surveillance system seriously underestimate the real disease burden of AGWs.",2017 Dec 20,"['Wei, Feixue', 'Sheng, Wei', 'Wu, Xin', 'Yin, Kai', 'Lan, Jian', 'Huang, Yue', 'Ma, Xinjing', 'Zheng, Ya', 'Zhuang, Sijie', 'Huang, Shoujie', 'Su, Yingying', 'Li, Mingqiang', 'Wu, Ting', 'Zhang, Jun', 'Xia, Ningshao']",Emerg Microbes Infect,,,True
c73f20f4c23082587dce9f31bfd6f76d4a7ed6c0,PMC,"Avian Group D Rotaviruses: Structure, Epidemiology, Diagnosis, and Perspectives on Future Research Challenges",http://dx.doi.org/10.3390/pathogens6040053,PMC5750577,29064408,CC BY,"In 1981, a new virus (virus 132) was described for the first time with morphological and biochemical similarities to rotaviruses (RVs), but without antigenic similarity to any of the previously known rotavirus groups. Subsequently, it was re-designated as D/132, and formed a new serogroup among rotaviruses, the group D rotavirus (RVD). Since their identification, RVs are the leading cause of enteritis and diarrhea in humans and various animal species, and are also associated with abridged growth, particularly in avian species. Recently, RVD has been suggested to play a role in the pathogenesis of runting and stunting syndrome (RSS), alongside other viruses such as reovirus, astrovirus, coronavirus, and others, all of which cause colossal economic losses to the poultry industry. RVD has been reported from several countries worldwide, and to date, only one complete genome sequence for RVD is available. Neither an immunodiagnostic nor a vaccine is available for the detection and prevention of RVD infection. Despite our growing understanding about this particular group, questions remain regarding its exact prevalence and pathogenecity, and the disease-associated annual losses for the poultry industry. Here, we describe the current knowledge about the identification, epidemiology, diagnosis, and prevention of RVD in poultry.",2017 Oct 24,"['Deol, Pallavi', 'Kattoor, Jobin Jose', 'Sircar, Shubhankar', 'Ghosh, Souvik', 'Bányai, Krisztián', 'Dhama, Kuldeep', 'Malik, Yashpal Singh']",Pathogens,,,True
67979137f54d228fc6ce49d290c8caed8565abe7,PMC,"Avian Group D Rotaviruses: Structure, Epidemiology, Diagnosis, and Perspectives on Future Research Challenges",http://dx.doi.org/10.3390/pathogens6040053,PMC5750577,29064408,CC BY,"In 1981, a new virus (virus 132) was described for the first time with morphological and biochemical similarities to rotaviruses (RVs), but without antigenic similarity to any of the previously known rotavirus groups. Subsequently, it was re-designated as D/132, and formed a new serogroup among rotaviruses, the group D rotavirus (RVD). Since their identification, RVs are the leading cause of enteritis and diarrhea in humans and various animal species, and are also associated with abridged growth, particularly in avian species. Recently, RVD has been suggested to play a role in the pathogenesis of runting and stunting syndrome (RSS), alongside other viruses such as reovirus, astrovirus, coronavirus, and others, all of which cause colossal economic losses to the poultry industry. RVD has been reported from several countries worldwide, and to date, only one complete genome sequence for RVD is available. Neither an immunodiagnostic nor a vaccine is available for the detection and prevention of RVD infection. Despite our growing understanding about this particular group, questions remain regarding its exact prevalence and pathogenecity, and the disease-associated annual losses for the poultry industry. Here, we describe the current knowledge about the identification, epidemiology, diagnosis, and prevention of RVD in poultry.",2017 Oct 24,"['Deol, Pallavi', 'Kattoor, Jobin Jose', 'Sircar, Shubhankar', 'Ghosh, Souvik', 'Bányai, Krisztián', 'Dhama, Kuldeep', 'Malik, Yashpal Singh']",Pathogens,,,False
54b5dbd04a27590d6b7d0e0e899cbec62c9f91c0,PMC,Beyond Disaster Preparedness: Building a Resilience-Oriented Workforce for the Future,http://dx.doi.org/10.3390/ijerph14121563,PMC5750981,29236028,CC BY,"Enhancing citizens’ and communities’ resilience is critical to adapt successfully to ongoing challenges faced by communities, as well as acute shocks resulting from disasters. While significant progress has been made in this area, several research and practice gaps remain. A crucial next step to advance resilience is the development of a resilience-oriented workforce. This narrative review examines existing literature to determine key components of a resilience-oriented workforce, with a focus on organizational structures, training and education, and leadership models. Reviewed articles spanned a variety of study types, including needs assessments of existing workforce, program evaluations, and reviews/commentaries. A resilience-oriented workforce spans many disciplines and training programs will need to reflect that. It requires a collaborative organizational model that promotes information sharing structures. Leadership models should foster a balance between workforce autonomy and operation as a collective entity. Optimal strategies to develop a resilience-oriented workforce have yet to be realized and future research will need to collect and synthesize data to promote and evaluate the growth of this field.",2017 Dec 13,"['Madrigano, Jaime', 'Chandra, Anita', 'Costigan, Tracy', 'Acosta, Joie D.']",Int J Environ Res Public Health,,,True
811159783691dd3e398010444f7b1564bc885d08,PMC,Airborne or Fomite Transmission for Norovirus? A Case Study Revisited,http://dx.doi.org/10.3390/ijerph14121571,PMC5750989,29240665,CC BY,"Norovirus infection, a highly prevalent condition associated with a high rate of morbidity, comprises a significant health issue. Although norovirus transmission mainly occurs via the fecal-oral and vomit-oral routes, airborne transmission has been proposed in recent decades. This paper re-examines a previously described norovirus outbreak in a hotel restaurant wherein airborne transmission was originally inferred. Specifically, the original evidence that suggested airborne transmission was re-analyzed by exploring an alternative hypothesis: could this outbreak instead have occurred via fomite transmission? This re-analysis was based on whether fomite transmission could have yielded similar attack rate distribution patterns. Seven representative serving pathways used by waiters were considered, and the infection risk distributions of the alternative fomite transmission routes were predicted using a multi-agent model. These distributions were compared to the reported attack rate distribution in the original study using a least square methods approach. The results show that with some reasonable assumptions of human behavior patterns and parameter values, the attack rate distribution corresponded well with that of the infection risk via the fomite route. This finding offers an alternative interpretation of the transmission routes that underlay this particular norovirus outbreak and an important consideration in the development of infection control guidelines and the investigation of similar norovirus outbreaks in future.",2017 Dec 14,"['Xiao, Shenglan', 'Tang, Julian W.', 'Li, Yuguo']",Int J Environ Res Public Health,,,True
4acb83c4e07408c4c244a047ee85091c9e0a48ed,PMC,Airborne or Fomite Transmission for Norovirus? A Case Study Revisited,http://dx.doi.org/10.3390/ijerph14121571,PMC5750989,29240665,CC BY,"Norovirus infection, a highly prevalent condition associated with a high rate of morbidity, comprises a significant health issue. Although norovirus transmission mainly occurs via the fecal-oral and vomit-oral routes, airborne transmission has been proposed in recent decades. This paper re-examines a previously described norovirus outbreak in a hotel restaurant wherein airborne transmission was originally inferred. Specifically, the original evidence that suggested airborne transmission was re-analyzed by exploring an alternative hypothesis: could this outbreak instead have occurred via fomite transmission? This re-analysis was based on whether fomite transmission could have yielded similar attack rate distribution patterns. Seven representative serving pathways used by waiters were considered, and the infection risk distributions of the alternative fomite transmission routes were predicted using a multi-agent model. These distributions were compared to the reported attack rate distribution in the original study using a least square methods approach. The results show that with some reasonable assumptions of human behavior patterns and parameter values, the attack rate distribution corresponded well with that of the infection risk via the fomite route. This finding offers an alternative interpretation of the transmission routes that underlay this particular norovirus outbreak and an important consideration in the development of infection control guidelines and the investigation of similar norovirus outbreaks in future.",2017 Dec 14,"['Xiao, Shenglan', 'Tang, Julian W.', 'Li, Yuguo']",Int J Environ Res Public Health,,,True
711a278ba27cfbfa11c5585a117f63a464560de4,PMC,How Do the First Days Count? A Case Study of Qatar Experience in Emergency Risk Communication during the MERS-CoV Outbreak,http://dx.doi.org/10.3390/ijerph14121597,PMC5751014,29257053,CC BY,"This case study is the first to be developed in the Middle East region to document what happened during the response to the 2013 MERS outbreak in Qatar. It provides a description of key epidemiologic events and news released from a prime daily newspaper and main Emergency Risk Communication (ERC) actions that were undertaken by public health authorities. Using the Crisis and Emergency Risk Communication (CERC) theoretical framework, the study analyzes how the performed ERC strategies during the first days of the outbreak might have contributed to the outbreak management. Methods: MERS-CoV related events were chronologically tracked, together with the relevant stories that were published in a major newspaper over the course of three distinct phases of the epidemic. The collected media stories were then assessed against the practiced emergency risk communication (ERC) activities during the same time frame. Results: The Crisis & Emergency Risk Communication (CERC) framework was partially followed during the early days of the MERS-CoV epidemic, which were characterized by overwhelming uncertainty. The SCH’s commitment to a proactive and open risk communication strategy since day one, contributed to creating the SCH’s image as a credible source of information and allowed for the quick initiation of the overall response efforts. Yet, conflicting messages and over reassurance were among the observed pitfalls of the implemented ERC strategy. Conclusion: The adoption of CERC principles can help restore and maintain the credibility of responding agencies. Further work is needed to develop more rigorous and comprehensive research strategies that address sharing of information by mainstream as well as social media for a more accurate assessment of the impact of the ERC strategy.",2017 Dec 19,"['Nour, Mohamed', 'Alhajri, Mohd', 'Farag, Elmoubasher A. B. A.', 'Al-Romaihi, Hamad E.', 'Al-Thani, Mohamed', 'Al-Marri, Salih', 'Savoia, Elena']",Int J Environ Res Public Health,,,True
1e4181fec183b68f1c863a6465c4a39c867008dc,PMC,Virus taxonomy: the database of the International Committee on Taxonomy of Viruses (ICTV),http://dx.doi.org/10.1093/nar/gkx932,PMC5753373,29040670,CC BY,"The International Committee on Taxonomy of Viruses (ICTV) is charged with the task of developing, refining, and maintaining a universal virus taxonomy. This task encompasses the classification of virus species and higher-level taxa according to the genetic and biological properties of their members; naming virus taxa; maintaining a database detailing the currently approved taxonomy; and providing the database, supporting proposals, and other virus-related information from an open-access, public web site. The ICTV web site (http://ictv.global) provides access to the current taxonomy database in online and downloadable formats, and maintains a complete history of virus taxa back to the first release in 1971. The ICTV has also published the ICTV Report on Virus Taxonomy starting in 1971. This Report provides a comprehensive description of all virus taxa covering virus structure, genome structure, biology and phylogenetics. The ninth ICTV report, published in 2012, is available as an open-access online publication from the ICTV web site. The current, 10th report (http://ictv.global/report/), is being published online, and is replacing the previous hard-copy edition with a completely open access, continuously updated publication. No other database or resource exists that provides such a comprehensive, fully annotated compendium of information on virus taxa and taxonomy.",2018 Jan 4,"['Lefkowitz, Elliot J', 'Dempsey, Donald M', 'Hendrickson, Robert Curtis', 'Orton, Richard J', 'Siddell, Stuart G', 'Smith, Donald B']",Nucleic Acids Res,,,True
b808fdf8f60809c6d95eb9cee704290dc4af9111,PMC,Virus taxonomy: the database of the International Committee on Taxonomy of Viruses (ICTV),http://dx.doi.org/10.1093/nar/gkx932,PMC5753373,29040670,CC BY,"The International Committee on Taxonomy of Viruses (ICTV) is charged with the task of developing, refining, and maintaining a universal virus taxonomy. This task encompasses the classification of virus species and higher-level taxa according to the genetic and biological properties of their members; naming virus taxa; maintaining a database detailing the currently approved taxonomy; and providing the database, supporting proposals, and other virus-related information from an open-access, public web site. The ICTV web site (http://ictv.global) provides access to the current taxonomy database in online and downloadable formats, and maintains a complete history of virus taxa back to the first release in 1971. The ICTV has also published the ICTV Report on Virus Taxonomy starting in 1971. This Report provides a comprehensive description of all virus taxa covering virus structure, genome structure, biology and phylogenetics. The ninth ICTV report, published in 2012, is available as an open-access online publication from the ICTV web site. The current, 10th report (http://ictv.global/report/), is being published online, and is replacing the previous hard-copy edition with a completely open access, continuously updated publication. No other database or resource exists that provides such a comprehensive, fully annotated compendium of information on virus taxa and taxonomy.",2018 Jan 4,"['Lefkowitz, Elliot J', 'Dempsey, Donald M', 'Hendrickson, Robert Curtis', 'Orton, Richard J', 'Siddell, Stuart G', 'Smith, Donald B']",Nucleic Acids Res,,,False
46980d68b4e24f2abd5c94ce173c6f229cfb2162,PMC,Biopanning of polypeptides binding to bovine ephemeral fever virus G(1) protein from phage display peptide library,http://dx.doi.org/10.1186/s12917-017-1315-x,PMC5753476,29301517,CC BY,"BACKGROUND: The bovine ephemeral fever virus (BEFV) glycoprotein neutralization site 1 (also referred as G(1) protein), is a critical protein responsible for virus infectivity and eliciting immune-protection, however, binding peptides of BEFV G(1) protein are still unclear. Thus, the aim of the present study was to screen specific polypeptides, which bind BEFV G(1) protein with high-affinity and inhibit BEFV replication. METHODS: The purified BEFV G(1) was coated and then reacted with the M13-based Ph.D.-7 phage random display library. The peptides for target binding were automated sequenced after four rounds of enrichment biopanning. The amino acid sequences of polypeptide displayed on positive clones were deduced and the affinity of positive polypeptides with BEFV G(1) was assayed by ELISA. Then the roles of specific G(1)-binding peptides in the context of BEFV infection were analyzed. RESULTS: The results showed that 27 specific peptide ligands displaying 11 different amino acid sequences were obtained, and the T18 and T25 clone had a higher affinity to G(1) protein than the other clones. Then their antiviral roles of two phage clones (T25 and T18) showed that both phage polypeptide T25 and T18 exerted inhibition on BEFV replication compared to control group. Moreover, synthetic peptide based on T18 (HSIRYDF) and T25 (YSLRSDY) alone or combined use on BEFV replication showed that the synthetic peptides could effectively inhibit the formation of cytopathic plaque and significantly inhibit BEFV RNA replication in a dose-dependent manner. CONCLUSION: Two antiviral peptide ligands binding to bovine ephemeral fever virus G(1) protein from phage display peptide library were identified, which may provide a potential research tool for diagnostic reagents and novel antiviral agents. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-017-1315-x) contains supplementary material, which is available to authorized users.",2018 Jan 4,"['Hou, Peili', 'Zhao, Guimin', 'He, Chengqiang', 'Wang, Hongmei', 'He, Hongbin']",BMC Vet Res,,,True
432bff7a22efb0fd2d87b162ce6da91120d28cfe,PMC,Impact of influenza vaccine on childhood otitis media in Taiwan: A population-based study,http://dx.doi.org/10.1371/journal.pone.0190507,PMC5755876,29304178,CC BY,"PURPOSE: Acute otitis media (AOM) is a common infectious disease in children and usually accompanied by a preceding viral respiratory tract infection, especially in the preschool-age population. The study aimed to evaluate impact of influenza vaccine on childhood otitis media. METHODS: This retrospective cohort study included data for 803,592 children (<10 years old) recorded in Taiwan’s National Health Insurance Research Database. AOM incidence and tympanostomy tube insertion incidence in each influenza season before and after the introduction of traditional injectable trivalent influenza vaccine (TIV) were compared using the Poisson regression analysis to estimate the incidence rate ratios (IRRs) and 95% confidence intervals (CIs). RESULTS: In children < 2 years old, the age group eligible for free influenza vaccination, there was a significant reduction in seasonal AOM incidence after TIV introduction in 2004 (from 98.4 episodes/1000 person-seasons [95% CI: 96.4–100.5] to 66.1 episodes/1000 person-seasons [95% CI: 64–68.1]). In addition, with the increased vaccine coverage rate, the outpatient visits for AOM in the influenza season of 2005 and 2006 were significantly lower than that in 2004 (IRR = 0.85 and 0.80, respectively, p < 0.0001). CONCLUSIONS: A significant reduction in primary care consultations for children <2 years old was observed after the introduction of the TIV in Taiwan in 2004. With the increased vaccine coverage, there was an additional decline in 2005 and 2006. In addition of the direct protection provided by the vaccination, we believe that TIV may have induced some herd immunity that further contributed to the reduction in influenza attack rates and the rates of associated AOM in that age group. These reductions were observed only in vaccine-eligible children, while older children, who were not enrolled in the influenza vaccination program during the study period, have experienced increases in the AOM incidence during the 2004–2006 period compared to the 2000–2003 period.",2018 Jan 5,"['Wu, Pei-Wen', 'Huang, Chien-Chia', 'Chao, Wei-Chieh', 'Sun, Chi-Chin', 'Chiu, Cheng-Hsun', 'Lee, Ta-Jen']",PLoS One,,,True
f16640169870cf9f1a8e1eae725e8850b8551817,PMC,Bacterial ribonuclease binase exerts an intra-cellular anti-viral mode of action targeting viral RNAs in influenza a virus-infected MDCK-II cells,http://dx.doi.org/10.1186/s12985-017-0915-1,PMC5756404,29304825,CC BY,"BACKGROUND: Influenza is a severe contagious disease especially in children, elderly and immunocompromised patients. Beside vaccination, the discovery of new anti-viral agents represents an important strategy to encounter seasonal and pandemic influenza A virus (IAV) strains. The bacterial extra-cellular ribonuclease binase is a well-studied RNase from Bacillus pumilus. Treatment with binase was shown to improve survival of laboratory animals infected with different RNA viruses. Although binase reduced IAV titer in vitro and in vivo, the mode of action (MOA) of binase against IAV at the molecular level has yet not been studied in depth and remains elusive. METHODS: To analyze whether binase impairs virus replication by direct interaction with the viral particle we applied a hemagglutination inhibition assay and monitored the integrity of the viral RNA within the virus particle by RT-PCR. Furthermore, we used Western blot and confocal microscopy analysis to study whether binase can internalize into MDCK-II cells. By primer extension we examined the effect of binase on the integrity of viral RNAs within the cells and using a mini-genome system we explored the effect of binase on the viral expression. RESULTS: We show that (i) binase does not to attack IAV particle-protected viral RNA, (ii) internalized binase could be detected within the cytosol of MDCK-II cells and that (iii) binase impairs IAV replication by specifically degrading viral RNA species within the infected MDCK-II cells without obvious effect on cellular mRNAs. CONCLUSION: Our data provide novel evidence suggesting that binase is a potential anti-viral agent with specific intra-cellular MOA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-017-0915-1) contains supplementary material, which is available to authorized users.",2018 Jan 5,"['Shah Mahmud, Raihan', 'Mostafa, Ahmed', 'Müller, Christin', 'Kanrai, Pumaree', 'Ulyanova, Vera', 'Sokurenko, Yulia', 'Dzieciolowski, Julia', 'Kuznetsova, Irina', 'Ilinskaya, Olga', 'Pleschka, Stephan']",Virol J,,,False
144bd370f94a0844a954100eb08bf1df9403ddaf,PMC,Bacterial ribonuclease binase exerts an intra-cellular anti-viral mode of action targeting viral RNAs in influenza a virus-infected MDCK-II cells,http://dx.doi.org/10.1186/s12985-017-0915-1,PMC5756404,29304825,CC BY,"BACKGROUND: Influenza is a severe contagious disease especially in children, elderly and immunocompromised patients. Beside vaccination, the discovery of new anti-viral agents represents an important strategy to encounter seasonal and pandemic influenza A virus (IAV) strains. The bacterial extra-cellular ribonuclease binase is a well-studied RNase from Bacillus pumilus. Treatment with binase was shown to improve survival of laboratory animals infected with different RNA viruses. Although binase reduced IAV titer in vitro and in vivo, the mode of action (MOA) of binase against IAV at the molecular level has yet not been studied in depth and remains elusive. METHODS: To analyze whether binase impairs virus replication by direct interaction with the viral particle we applied a hemagglutination inhibition assay and monitored the integrity of the viral RNA within the virus particle by RT-PCR. Furthermore, we used Western blot and confocal microscopy analysis to study whether binase can internalize into MDCK-II cells. By primer extension we examined the effect of binase on the integrity of viral RNAs within the cells and using a mini-genome system we explored the effect of binase on the viral expression. RESULTS: We show that (i) binase does not to attack IAV particle-protected viral RNA, (ii) internalized binase could be detected within the cytosol of MDCK-II cells and that (iii) binase impairs IAV replication by specifically degrading viral RNA species within the infected MDCK-II cells without obvious effect on cellular mRNAs. CONCLUSION: Our data provide novel evidence suggesting that binase is a potential anti-viral agent with specific intra-cellular MOA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-017-0915-1) contains supplementary material, which is available to authorized users.",2018 Jan 5,"['Shah Mahmud, Raihan', 'Mostafa, Ahmed', 'Müller, Christin', 'Kanrai, Pumaree', 'Ulyanova, Vera', 'Sokurenko, Yulia', 'Dzieciolowski, Julia', 'Kuznetsova, Irina', 'Ilinskaya, Olga', 'Pleschka, Stephan']",Virol J,,,True
778e39cb165c72b4245262781d804c4e1f6da3d7,PMC,Role of microRNAs in doxorubicin-induced cardiotoxicity: an overview of preclinical models and cancer patients,http://dx.doi.org/10.1007/s10741-017-9653-0,PMC5756562,28944400,CC BY,"Cardiotoxicity is a well-known side effect of doxorubicin (DOX), but the mechanisms leading to this phenomenon are still not completely clear. Prediction of drug-induced dysfunction onset is difficult and is still largely based on detection of cardiac troponin (cTn), a circulating marker of heart damage. In the last years, several investigations focused on the possible involvement of microRNAs (miRNAs) in DOX-induced toxicity in vitro, with contrasting results. Recently, several groups employed animal models to mimic patient’s condition, investigate the biological pathways perturbed by DOX, and identify diagnostic markers of cardiotoxicity. We reviewed the results from several studies investigating cardiac miRNAs expression in rodent models of DOX-treatment. We also discussed the data from two publications indicating the possible use of circulating miRNA as biomarkers of DOX-induced cardiotoxicity. Unfortunately, limited information was derived from these studies, as selection methods of candidate-miRNAs and heterogeneity in cardiotoxicity assessment greatly hampered the novelty and robustness of the findings. Nevertheless, at least one circulating miRNA, miR-1, showed a good potential as early biomarker of drug-mediated cardiac dysfunction onset. The use of animal models to investigate DOX-induced cardiotoxicity surely helps narrowing the gap between basic research and clinical practice. Despite this, several issues, including selection of relevant miRNAs and less-than-optimal assessment of cardiotoxicity, greatly limited the results obtained so far. Nonetheless, the association of patients-based studies with the use of preclinical models may be the key to address the many unanswered questions regarding the pathophysiology and early detection of cardiotoxicity.",2018 Sep 25,"['Ruggeri, Clarissa', 'Gioffré, Sonia', 'Achilli, Felice', 'Colombo, Gualtiero I.', 'D’Alessandra, Yuri']",Heart Fail Rev,,,True
28d395784208073fa0bd75540cfed74a2018061d,PMC,Efficacy of a Virus-Like Nanoparticle As Treatment for a Chronic Viral Infection Is Hindered by IRAK1 Regulation and Antibody Interference,http://dx.doi.org/10.3389/fimmu.2017.01885,PMC5758502,29354118,CC BY,"Although vaccination has been an effective way of preventing infections ever since the eighteenth century, the generation of therapeutic vaccines and immunotherapies is still a work in progress. A number of challenges impede the development of these therapeutic approaches such as safety issues related to the administration of whole pathogens whether attenuated or inactivated. One safe alternative to classical vaccination methods gaining recognition is the use of nanoparticles, whether synthetic or naturally derived. We have recently demonstrated that the papaya mosaic virus (PapMV)-like nanoparticle can be used as a prophylactic vaccine against various viral and bacterial infections through the induction of protective humoral and cellular immune responses. Moreover, PapMV is also very efficient when used as an immune adjuvant in an immunotherapeutic setting at slowing down the growth of aggressive mouse melanoma tumors in a type I interferon (IFN-I)-dependent manner. In the present study, we were interested in exploiting the capacity of PapMV of inducing robust IFN-I production as treatment for the chronic viral infection model lymphocytic choriomeningitis virus (LCMV) clone 13 (Cl13). Treatment of LCMV Cl13-infected mice with two systemic administrations of PapMV was ineffective, as shown by the lack of changes in viral titers and immune response to LCMV following treatment. Moreover, IFN-α production following PapMV administration was almost completely abolished in LCMV-infected mice. To better isolate the mechanisms at play, we determined the influence of a pretreatment with PapMV on secondary PapMV administration, therefore eliminating potential variables emanating from the infection. Pretreatment with PapMV led to the same outcome as an LCMV infection in that IFN-α production following secondary PapMV immunization was abrogated for up to 50 days while immune activation was also dramatically impaired. We showed that two distinct and overlapping mechanisms were responsible for this outcome. While short-term inhibition was partially the result of interleukin-1 receptor-associated kinase 1 degradation, a crucial component of the toll-like receptor 7 signaling pathway, long-term inhibition was mainly due to interference by PapMV-specific antibodies. Thus, we identified a possible pitfall in the use of virus-like particles for the systemic treatment of chronic viral infections and discuss mitigating alternatives to circumvent these potential problems.",2018 Jan 4,"['Chartrand, Karine', 'Lebel, Marie-Ève', 'Tarrab, Esther', 'Savard, Pierre', 'Leclerc, Denis', 'Lamarre, Alain']",Front Immunol,,,True
2392e0e02b81ed3565b792e9794d50994acc8535,PMC,Inhibiting the Ins and Outs of HIV Replication: Cell-Intrinsic Antiretroviral Restrictions at the Plasma Membrane,http://dx.doi.org/10.3389/fimmu.2017.01853,PMC5758531,29354117,CC BY,"Like all viruses, human immunodeficiency viruses (HIVs) and their primate lentivirus relatives must enter cells in order to replicate and, once produced, new virions need to exit to spread to new targets. These processes require the virus to cross the plasma membrane of the cell twice: once via fusion mediated by the envelope glycoprotein to deliver the viral core into the cytosol; and secondly by ESCRT-mediated scission of budding virions during release. This physical barrier thus presents a perfect location for host antiviral restrictions that target enveloped viruses in general. In this review we will examine the current understanding of innate host antiviral defences that inhibit these essential replicative steps of primate lentiviruses associated with the plasma membrane, the mechanism by which these viruses have adapted to evade such defences, and the role that this virus/host battleground plays in the transmission and pathogenesis of HIV/AIDS.",2018 Jan 4,"['Foster, Toshana L.', 'Pickering, Suzanne', 'Neil, Stuart J. D.']",Front Immunol,,,True
82b043ec316b0bfb8350d65b09f6028d4ea9e564,PMC,Know Your Enemy: Successful Bioinformatic Approaches to Predict Functional RNA Structures in Viral RNAs,http://dx.doi.org/10.3389/fmicb.2017.02582,PMC5758548,29354101,CC BY,"Structured RNA elements may control virus replication, transcription and translation, and their distinct features are being exploited by novel antiviral strategies. Viral RNA elements continue to be discovered using combinations of experimental and computational analyses. However, the wealth of sequence data, notably from deep viral RNA sequencing, viromes, and metagenomes, necessitates computational approaches being used as an essential discovery tool. In this review, we describe practical approaches being used to discover functional RNA elements in viral genomes. In addition to success stories in new and emerging viruses, these approaches have revealed some surprising new features of well-studied viruses e.g., human immunodeficiency virus, hepatitis C virus, influenza, and dengue viruses. Some notable discoveries were facilitated by new comparative analyses of diverse viral genome alignments. Importantly, comparative approaches for finding RNA elements embedded in coding and non-coding regions differ. With the exponential growth of computer power we have progressed from stem-loop prediction on single sequences to cutting edge 3D prediction, and from command line to user friendly web interfaces. Despite these advances, many powerful, user friendly prediction tools and resources are underutilized by the virology community.",2018 Jan 4,"['Lim, Chun Shen', 'Brown, Chris M.']",Front Microbiol,,,True
e7910acd7e2772df933ee8161c68baf67cc4991d,PMC,Ultrastructural Localization and Molecular Associations of HCV Capsid Protein in Jurkat T Cells,http://dx.doi.org/10.3389/fmicb.2017.02595,PMC5758585,29354102,CC BY,"Hepatitis C virus core protein is a highly basic viral protein that multimerizes with itself to form the viral capsid. When expressed in CD4(+) T lymphocytes, it can induce modifications in several essential cellular and biological networks. To shed light on the mechanisms underlying the alterations caused by the viral protein, we have analyzed HCV-core subcellular localization and its associations with host proteins in Jurkat T cells. In order to investigate the intracellular localization of Hepatitis C virus core protein, we have used a lentiviral system to transduce Jurkat T cells and subsequently localize the protein using immunoelectron microscopy techniques. We found that in Jurkat T cells, Hepatitis C virus core protein mostly localizes in the nucleus and specifically in the nucleolus. In addition, we performed pull-down assays combined with Mass Spectrometry Analysis, to identify proteins that associate with Hepatitis C virus core in Jurkat T cells. We found proteins such as NOLC1, PP1γ, ILF3, and C1QBP implicated in localization and/or traffic to the nucleolus. HCV-core associated proteins are implicated in RNA processing and RNA virus infection as well as in functions previously shown to be altered in Hepatitis C virus core expressing CD4(+) T cells, such as cell cycle delay, decreased proliferation, and induction of a regulatory phenotype. Thus, in the current work, we show the ultrastructural localization of Hepatitis C virus core and the first profile of HCV core associated proteins in T cells, and we discuss the functions and interconnections of these proteins in molecular networks where relevant biological modifications have been described upon the expression of Hepatitis C virus core protein. Thereby, the current work constitutes a necessary step toward understanding the mechanisms underlying HCV core mediated alterations that had been described in relevant biological processes in CD4(+) T cells.",2018 Jan 4,"['Fernández-Ponce, Cecilia', 'Durán-Ruiz, Maria C.', 'Narbona-Sánchez, Isaac', 'Muñoz-Miranda, Juan P.', 'Arbulo-Echevarria, Mikel M.', 'Serna-Sanz, Antonio', 'Baumann, Christian', 'Litrán, Rocío', 'Aguado, Enrique', 'Bloch, Wilhelm', 'García-Cozar, Francisco']",Front Microbiol,,,True
0577bfc182ea9062ae7d4e4c419a84777b734a4c,PMC,Application of extracorporeal membrane oxygenation in patients with severe acute respiratory distress syndrome induced by avian influenza A (H7N9) viral pneumonia: national data from the Chinese multicentre collaboration,http://dx.doi.org/10.1186/s12879-017-2903-x,PMC5759204,29310581,CC BY,"BACKGROUND: Evidence concerning the efficacy and safety of extracorporeal membrane oxygenation (ECMO) in patients with influenza A (H7N9) has been was limited to case reports. Our study is aimed to investigate the current application, efficacy and safety of ECMO in for severe H7N9 pneumonia-associated acute respiratory distress syndrome (ARDS) in the Chinese population. METHODS: A multicentre retrospective cohort study was conducted at 20 hospitals that admitted patients with avian influenza A (H7N9) viral pneumonia patients’ admission from 9 provinces in China between October 1, 2016, and March 1, 2017. Data from the National Health and Family Planning Commission of China, including general conditions, outcomes and ECMO management, were analysed. Then, successfully weaned and unsuccessfully weaned groups were compared. RESULTS: A total of 35 patients, aged 57 ± 1 years, were analysed; 65.7% of patients were male with 63% mortality. All patients underwent invasive positive pressure ventilation (IPPV), and rescue ventilation strategies were implemented for 23 cases (65.7%) with an average IPPV duration of 5 ± 1 d, PaO(2)/FiO(2) of 78 ± 23 mmHg, tidal volume (VT) of 439 ± 61 ml and plateau pressure (P(plat)) of 29 ± 8 cmH(2)O pre-ECMO. After 48 h on ECMO, PaO(2) improved from 56 ± 21 mmHg to 90 ± 24 mmHg and PaCO(2) declined from 52 ± 24 mmHg to 38 ± 24 mmHg. Haemorrhage, ventilator-associated pneumonia (VAP) and barotrauma occurred in 45.7%, 60% and 8.6% of patients, respectively. Compared with successfully weaned patients (n = 14), the 21 unsuccessfully weaned patients had a longer duration of IPPV pre-ECMO (6 ± 4 d vs. 2 ± 1 d, P < 0.01) as well as a higher P(plat) (25 ± 5 cmH(2)O vs. 21 ± 3 cmH(2)O, P < 0.05) and VT (343 ± 96 ml vs. 246 ± 93 ml, P < 0.05) after 48 h on ECMO support. Furthermore, the unsuccessfully weaned group had a higher mortality (100% vs. 7.1%, P < 0.01) with more haemorrhage (77.3% vs. 28.6%, P < 0.01). CONCLUSIONS: ECMO is effective at improving oxygenation and ventilation of patients with avian influenza A (H7N9) induced severe ARDS. Early initiation of ECMO with appropriate IPPV settings and anticoagulation strategies are necessary to reduce complications.",2018 Jan 8,"['Huang, Linna', 'Zhang, Wei', 'Yang, Yi', 'Wu, Wenjuan', 'Lu, Weihua', 'Xue, Han', 'Zhao, Hongsheng', 'Wu, Yunfu', 'Shang, Jia', 'Cai, Lihua', 'Liu, Long', 'Liu, Donglin', 'Wang, Yeming', 'Cao, Bin', 'Zhan, Qingyuan', 'Wang, Chen']",BMC Infect Dis,,,True
f19e6df5a006cb83449f1ec0dd16a9aa6703b0dc,PMC,Evaluation of green tea extract as a safe personal hygiene against viral infections,http://dx.doi.org/10.1186/s13036-017-0092-1,PMC5759362,29339972,CC BY,"BACKGROUND: Viral infections often pose tremendous public health concerns as well as economic burdens. Despite the availability of vaccines or antiviral drugs, personal hygiene is considered as effective means as the first-hand measure against viral infections. The green tea catechins, in particular, epigallocatechin-3-gallate (EGCG), are known to exert potent antiviral activity. In this study, we evaluated the green tea extract as a safe personal hygiene against viral infections. RESULTS: Using the influenza virus A/Puerto Rico/8/34 (H1N1) as a model, we examined the duration of the viral inactivating activity of green tea extract (GTE) under prolonged storage at various temperature conditions. Even after the storage for 56 days at different temperatures, 0.1% GTE completely inactivated 10(6) PFU of the virus (6 log(10) reduction), and 0.01% and 0.05% GTE resulted in 2 log(10) reduction of the viral titers. When supplemented with 2% citric acid, 0.1% sodium benzoate, and 0.2% ascorbic acid as anti-oxidant, the inactivating activity of GTE was temporarily compromised during earlier times of storage. However, the antiviral activity of the GTE was steadily recovered up to similar levels with those of the same concentrations of GTE without the supplements, effectively prolonging the duration of the virucidal function over extended period. Cryo-EM and DLS analyses showed a slight increase in the overall size of virus particles by GTE treatment. The results suggest that the virucidal activity of GTE is mediated by oxidative crosslinking of catechins to the viral proteins and the change of physical properties of viral membranes. CONCLUSIONS: The durability of antiviral effects of GTE was examined as solution type and powder types over extended periods at various temperature conditions using human influenza A/H1N1 virus. GTE with supplements demonstrated potent viral inactivating activity, resulting in greater than 4 log(10) reduction of viral titers even after storage for up to two months at a wide range of temperatures. These data suggest that GTE-based antiviral agents could be formulated as a safe and environmentally friendly personal hygiene against viral infections.",2018 Jan 8,"['Lee, Yun Ha', 'Jang, Yo Han', 'Kim, Young-Seok', 'Kim, Jinku', 'Seong, Baik Lin']",J Biol Eng,,,True
cc6fc7b79884d2ba613637a7a206dfb47233cccb,PMC,Nitric oxide induced by Indian ginseng root extract inhibits Infectious Bursal Disease virus in chicken embryo fibroblasts in vitro,http://dx.doi.org/10.1186/s40781-017-0156-2,PMC5759882,29340165,CC BY,"Infectious Bursal Disease is a severe viral disease of chicken responsible for serious economic losses to poultry farmers. The causative agent, Infectious Bursal Disease virus, is inhibited by nitric oxide. Root extract of the Indian ginseng, Withania somnifera, inhibits Infectious Bursal Disease virus in vitro. Also, Withania somnifera root extract is known to induce nitric oxide production in vitro. Therefore, the present study was undertaken to determine if the inhibitory activity of Withania somnifera against Infectious Bursal Disease virus was based on the production of nitric oxide. We show that besides other mechanisms, the inhibition of Infectious Bursal Disease virus by Withania somnifera involves the production of nitric oxide. Our results also highlight the paradoxical role of nitric oxide in the pathogenesis of Infectious Bursal Disease.",2018 Jan 8,"['Ganguly, Bhaskar', 'Umapathi, Vijaypillai', 'Rastogi, Sunil Kumar']",J Anim Sci Technol,,,True
c988e746b24092faa25d2a025870300642a205e3,PMC,Exhaled air dispersion during bag-mask ventilation and sputum suctioning - Implications for infection control,http://dx.doi.org/10.1038/s41598-017-18614-1,PMC5760517,29317750,CC BY,"Mask ventilation and coughing during oro-tracheal suctioning produce aerosols that enhance nosocomial transmission of respiratory infections. We examined the extent of exhaled air dispersion from a human-patient-simulator during mask ventilation by different groups of healthcare workers and coughing bouts. The simulator was programmed to mimic varying severity of lung injury. Exhaled airflow was marked with tiny smoke particles, and highlighted by laser light-sheet. We determined the normalized exhaled air concentration in the leakage jet plume from the light scattered by smoke particles. Smoke concentration ≥20% was considered as significant exposure. Exhaled air leaked from mask-face interface in the transverse plane was most severe (267 ± 44 mm) with Ambu silicone resuscitator performed by nurses. Dispersion was however similar among anesthesiologists/intensivists, respiratory physicians and medical students using Ambu or Laerdal silicone resuscitator, p = 0.974. The largest dispersion was 860 ± 93 mm during normal coughing effort without tracheal intubation and decreased with worsening coughing efforts. Oro-tracheal suctioning reduced dispersion significantly, p < 0.001, and was more effective when applied continuously. Skills to ensure good fit during mask ventilation are important in preventing air leakage through the mask-face interface. Continuous oro-tracheal suctioning minimized exhaled air dispersion during coughing bouts when performing aerosol-generating procedures.",2018 Jan 9,"['Chan, Matthew T. V.', 'Chow, Benny K.', 'Lo, Thomas', 'Ko, Fanny W.', 'Ng, Susanna S.', 'Gin, Tony', 'Hui, David S.']",Sci Rep,,,False
2bd1d7992ad099b99b495fdd79493a00210bcbe0,PMC,Exhaled air dispersion during bag-mask ventilation and sputum suctioning - Implications for infection control,http://dx.doi.org/10.1038/s41598-017-18614-1,PMC5760517,29317750,CC BY,"Mask ventilation and coughing during oro-tracheal suctioning produce aerosols that enhance nosocomial transmission of respiratory infections. We examined the extent of exhaled air dispersion from a human-patient-simulator during mask ventilation by different groups of healthcare workers and coughing bouts. The simulator was programmed to mimic varying severity of lung injury. Exhaled airflow was marked with tiny smoke particles, and highlighted by laser light-sheet. We determined the normalized exhaled air concentration in the leakage jet plume from the light scattered by smoke particles. Smoke concentration ≥20% was considered as significant exposure. Exhaled air leaked from mask-face interface in the transverse plane was most severe (267 ± 44 mm) with Ambu silicone resuscitator performed by nurses. Dispersion was however similar among anesthesiologists/intensivists, respiratory physicians and medical students using Ambu or Laerdal silicone resuscitator, p = 0.974. The largest dispersion was 860 ± 93 mm during normal coughing effort without tracheal intubation and decreased with worsening coughing efforts. Oro-tracheal suctioning reduced dispersion significantly, p < 0.001, and was more effective when applied continuously. Skills to ensure good fit during mask ventilation are important in preventing air leakage through the mask-face interface. Continuous oro-tracheal suctioning minimized exhaled air dispersion during coughing bouts when performing aerosol-generating procedures.",2018 Jan 9,"['Chan, Matthew T. V.', 'Chow, Benny K.', 'Lo, Thomas', 'Ko, Fanny W.', 'Ng, Susanna S.', 'Gin, Tony', 'Hui, David S.']",Sci Rep,,,True
0bd9e38537d45c72b8507471690027a78f8f4584,PMC,Regulation of RIG-I Activation by K63-Linked Polyubiquitination,http://dx.doi.org/10.3389/fimmu.2017.01942,PMC5760545,29354136,CC BY,"RIG-I is a pattern recognition receptor and recognizes cytoplasmic viral double-stranded RNA (dsRNA). Influenza A virus, hepatitis C virus, and several other pathogenic viruses are mainly recognized by RIG-I, resulting in the activation of the innate immune responses. The protein comprises N-terminal two caspase activation and recruitment domains (2CARDs), an RNA helicase domain, and the C-terminal domain (CTD). The CTD recognizes 5′-triphosphate viral dsRNA. After recognition of viral dsRNA, the protein harbors K63-linked polyubiquitination essential for RIG-I activation. First, it was reported that TRIM25 ubiquitin ligase delivered K63-linked polyubiquitin moiety to the 2CARDs. The polyubiquitin chain stabilizes a structure called the 2CARD tetramer, in which four 2CARDs assemble and make a core that promotes the aggregation of the mitochondrial antiviral-signaling (MAVS) protein on mitochondria. MAVS aggregation then triggers the signal to induce the innate immune responses. However, subsequent studies have reported that Riplet, MEX3C, and TRIM4 ubiquitin ligases are also involved in K63-linked polyubiquitination and the activation of RIG-I. MEX3C and TRIM4 mediate polyubiquitination of the 2CARDs. By contrast, Riplet ubiquitinates the CTD. The physiological significance of each ubiquitin ligases has been shown by knockout and knockdown studies, but there appears to be contradictory to evidence reported in the literature. In this review, we summarize recent findings related to K63-linked polyubiquitination and propose a model that could reconcile current contradictory theories. We also discuss the physiological significance of the ubiquitin ligases in the immune system against viral infection.",2018 Jan 5,"['Okamoto, Masaaki', 'Kouwaki, Takahisa', 'Fukushima, Yoshimi', 'Oshiumi, Hiroyuki']",Front Immunol,,,True
36dce9f7118e056798289b0019752f51e83568d9,PMC,Development and Validation of a Serologic Test Panel for Detection of Powassan Virus Infection in U.S. Patients Residing in Regions Where Lyme Disease Is Endemic,http://dx.doi.org/10.1128/mSphere.00467-17,PMC5760746,29359181,CC BY,"Powassan virus (POWV) is an emerging tick-borne arbovirus presenting a public health threat in North America. POWV lineage II, also known as deer tick virus, is the strain of the virus most frequently found in Ixodes scapularis ticks and is implicated in most cases of POWV encephalitis in the United States. Currently, no commercial tests are available to detect POWV exposure in tick-borne disease (TBD) patients. We describe here the development and analytical validation of a serologic test panel to detect POWV infections. The panel uses an indirect enzyme immunoassay (EIA) to screen. EIA-positive samples reflex to a laboratory-developed, POWV-specific immunofluorescence assay (IFA). The analytical sensitivity of the test panel was 89%, and the limit of detection was a plaque reduction neutralization test (PRNT) titer of 1:20. The analytical specificity was 100% for the IgM assay and 65% for the IgG assay when heterologous-flavivirus-positive samples were tested. On samples collected from regions where Lyme disease is endemic, seroprevalence for POWV in TBD samples was 9.4% (10 of 106) versus 2% when tested with non-TBD samples (2 of 100, P = 0.034). No evidence of POWV infection was seen in samples collected from a region where Lyme disease was not endemic (0 of 22). This test panel provides a sensitive and specific platform for detecting a serologic response to POWV early in the course of infection when neutralizing antibodies may not be detectable. Combined with clinical history, the panel is an effective tool for identifying acute POWV infection. IMPORTANCE Approximately 100 cases of POWV disease were reported in the United States over the past 10 years. Most cases have occurred in the Northeast (52) and Great Lakes (45) regions (https://www.cdc.gov/powassan/statistics.html). The prevalence of POWV in ticks and mammals is increasing, and POWV poses an increasing threat in a greater geographical range. In areas of the Northeast and Midwest where Lyme disease is endemic, POWV testing is recommended for patients with a recent tick bite, patients with Lyme disease who have been treated with antibiotics, or patients with a tick exposure who have tested negative for Lyme disease or other tick-borne illnesses and have persistent symptoms consistent with posttreatment Lyme disease. Testing could also benefit patients with tick exposure and unexplained neurologic symptoms and chronic fatigue syndrome (CFS) patients with known tick exposure. Until now, diagnostic testing for Powassan virus has not been commercially available and has been limited to patients presenting with severe, neurologic complications. The lack of routine testing for Powassan virus in patients with suspected tick-borne disease means that little information is available regarding the overall prevalence of the virus and the full spectrum of clinical symptoms associated with infection. As Ixodes scapularis is the tick vector for Powassan virus and multiple other tick-borne pathogens, including the Lyme disease bacterium, Borrelia burgdorferi, the clinical presentations and long-term outcomes of Powassan virus infection and concurrent infection with other tick-borne disease pathogens remain unknown.",2018 Jan 10,"['Thomm, Angela M.', 'Schotthoefer, Anna M.', 'Dupuis, Alan P.', 'Kramer, Laura D.', 'Frost, Holly M.', 'Fritsche, Thomas R.', 'Harrington, Yvette A.', 'Knox, Konstance K.', 'Kehl, Sue C.']",mSphere,,,True
f4cebabd74b16e710fb41a737d8ef84b7d565d8d,PMC,"A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies",http://dx.doi.org/10.1038/mp.2017.54,PMC5761721,28373692,CC BY,"Microtubule severing enzymes implement a diverse range of tissue-specific molecular functions throughout development and into adulthood. Although microtubule severing is fundamental to many dynamic neural processes, little is known regarding the role of the family member Katanin p60 subunit A-like 1, KATNAL1, in central nervous system (CNS) function. Recent studies reporting that microdeletions incorporating the KATNAL1 locus in humans result in intellectual disability and microcephaly suggest that KATNAL1 may play a prominent role in the CNS; however, such associations lack the functional data required to highlight potential mechanisms which link the gene to disease symptoms. Here we identify and characterise a mouse line carrying a loss of function allele in Katnal1. We show that mutants express behavioural deficits including in circadian rhythms, sleep, anxiety and learning/memory. Furthermore, in the brains of Katnal1 mutant mice we reveal numerous morphological abnormalities and defects in neuronal migration and morphology. Furthermore we demonstrate defects in the motile cilia of the ventricular ependymal cells of mutants, suggesting a role for Katnal1 in the development of ciliary function. We believe the data we present here are the first to associate KATNAL1 with such phenotypes, demonstrating that the protein plays keys roles in a number of processes integral to the development of neuronal function and behaviour.",2018 Apr 4,"['Banks, G', 'Lassi, G', 'Hoerder-Suabedissen, A', 'Tinarelli, F', 'Simon, M M', 'Wilcox, A', 'Lau, P', 'Lawson, T N', 'Johnson, S', 'Rutman, A', 'Sweeting, M', 'Chesham, J E', 'Barnard, A R', 'Horner, N', 'Westerberg, H', 'Smith, L B', 'Molnár, Z', 'Hastings, M H', 'Hirst, R A', 'Tucci, V', 'Nolan, P M']",Mol Psychiatry,,,True
dc3150dec198edfa1fd0127b946c9e65e41d1172,PMC,The impact of regular school closure on seasonal influenza epidemics: a data-driven spatial transmission model for Belgium,http://dx.doi.org/10.1186/s12879-017-2934-3,PMC5764028,29321005,CC BY,"BACKGROUND: School closure is often considered as an option to mitigate influenza epidemics because of its potential to reduce transmission in children and then in the community. The policy is still however highly debated because of controversial evidence. Moreover, the specific mechanisms leading to mitigation are not clearly identified. METHODS: We introduced a stochastic spatial age-specific metapopulation model to assess the role of holiday-associated behavioral changes and how they affect seasonal influenza dynamics. The model is applied to Belgium, parameterized with country-specific data on social mixing and travel, and calibrated to the 2008/2009 influenza season. It includes behavioral changes occurring during weekend vs. weekday, and holiday vs. school-term. Several experimental scenarios are explored to identify the relevant social and behavioral mechanisms. RESULTS: Stochastic numerical simulations show that holidays considerably delay the peak of the season and mitigate its impact. Changes in mixing patterns are responsible for the observed effects, whereas changes in travel behavior do not alter the epidemic. Weekends are important in slowing down the season by periodically dampening transmission. Christmas holidays have the largest impact on the epidemic, however later school breaks may help in reducing the epidemic size, stressing the importance of considering the full calendar. An extension of the Christmas holiday of 1 week may further mitigate the epidemic. CONCLUSION: Changes in the way individuals establish contacts during holidays are the key ingredient explaining the mitigating effect of regular school closure. Our findings highlight the need to quantify these changes in different demographic and epidemic contexts in order to provide accurate and reliable evaluations of closure effectiveness. They also suggest strategic policies in the distribution of holiday periods to minimize the epidemic impact. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-017-2934-3) contains supplementary material, which is available to authorized users.",2018 Jan 10,"['Luca, Giancarlo De', 'Kerckhove, Kim Van', 'Coletti, Pietro', 'Poletto, Chiara', 'Bossuyt, Nathalie', 'Hens, Niel', 'Colizza, Vittoria']",BMC Infect Dis,,,False
faf7a4e9db24c30637224f708ad868ecfc1d9da6,PMC,The impact of regular school closure on seasonal influenza epidemics: a data-driven spatial transmission model for Belgium,http://dx.doi.org/10.1186/s12879-017-2934-3,PMC5764028,29321005,CC BY,"BACKGROUND: School closure is often considered as an option to mitigate influenza epidemics because of its potential to reduce transmission in children and then in the community. The policy is still however highly debated because of controversial evidence. Moreover, the specific mechanisms leading to mitigation are not clearly identified. METHODS: We introduced a stochastic spatial age-specific metapopulation model to assess the role of holiday-associated behavioral changes and how they affect seasonal influenza dynamics. The model is applied to Belgium, parameterized with country-specific data on social mixing and travel, and calibrated to the 2008/2009 influenza season. It includes behavioral changes occurring during weekend vs. weekday, and holiday vs. school-term. Several experimental scenarios are explored to identify the relevant social and behavioral mechanisms. RESULTS: Stochastic numerical simulations show that holidays considerably delay the peak of the season and mitigate its impact. Changes in mixing patterns are responsible for the observed effects, whereas changes in travel behavior do not alter the epidemic. Weekends are important in slowing down the season by periodically dampening transmission. Christmas holidays have the largest impact on the epidemic, however later school breaks may help in reducing the epidemic size, stressing the importance of considering the full calendar. An extension of the Christmas holiday of 1 week may further mitigate the epidemic. CONCLUSION: Changes in the way individuals establish contacts during holidays are the key ingredient explaining the mitigating effect of regular school closure. Our findings highlight the need to quantify these changes in different demographic and epidemic contexts in order to provide accurate and reliable evaluations of closure effectiveness. They also suggest strategic policies in the distribution of holiday periods to minimize the epidemic impact. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-017-2934-3) contains supplementary material, which is available to authorized users.",2018 Jan 10,"['Luca, Giancarlo De', 'Kerckhove, Kim Van', 'Coletti, Pietro', 'Poletto, Chiara', 'Bossuyt, Nathalie', 'Hens, Niel', 'Colizza, Vittoria']",BMC Infect Dis,,,True
eceb1667ac6722e9131eb7d0f560a7f76bfb25f1,PMC,Genetic diversity and recombination of enterovirus G strains in Japanese pigs: High prevalence of strains carrying a papain-like cysteine protease sequence in the enterovirus G population,http://dx.doi.org/10.1371/journal.pone.0190819,PMC5764308,29324778,CC BY,"To study the genetic diversity of enterovirus G (EV-G) among Japanese pigs, metagenomics sequencing was performed on fecal samples from pigs with or without diarrhea, collected between 2014 and 2016. Fifty-nine EV-G sequences, which were >5,000 nucleotides long, were obtained. By complete VP1 sequence analysis, Japanese EV-G isolates were classified into G1 (17 strains), G2 (four strains), G3 (22 strains), G4 (two strains), G6 (two strains), G9 (six strains), G10 (five strains), and a new genotype (one strain). Remarkably, 16 G1 and one G2 strain identified in diarrheic (23.5%; four strains) or normal (76.5%; 13 strains) fecal samples possessed a papain-like cysteine protease (PL-CP) sequence, which was recently found in the USA and Belgium in the EV-G genome, at the 2C–3A junction site. This paper presents the first report of the high prevalence of viruses carrying PL-CP in the EV-G population. Furthermore, possible inter- and intragenotype recombination events were found among EV-G strains, including G1-PL-CP strains. Our findings may advance the understanding of the molecular epidemiology and genetic evolution of EV-Gs.",2018 Jan 11,"['Tsuchiaka, Shinobu', 'Naoi, Yuki', 'Imai, Ryo', 'Masuda, Tsuneyuki', 'Ito, Mika', 'Akagami, Masataka', 'Ouchi, Yoshinao', 'Ishii, Kazuo', 'Sakaguchi, Shoichi', 'Omatsu, Tsutomu', 'Katayama, Yukie', 'Oba, Mami', 'Shirai, Junsuke', 'Satani, Yuki', 'Takashima, Yasuhiro', 'Taniguchi, Yuji', 'Takasu, Masaki', 'Madarame, Hiroo', 'Sunaga, Fujiko', 'Aoki, Hiroshi', 'Makino, Shinji', 'Mizutani, Tetsuya', 'Nagai, Makoto']",PLoS One,,,True
e209784c9a22ca29bf423b8d77359142db053182,PMC,Regulation of influenza virus replication by Wnt/β-catenin signaling,http://dx.doi.org/10.1371/journal.pone.0191010,PMC5764324,29324866,CC BY,"Wnt/β-catenin signaling is an essential pathway in cell cycle control. Dysregulation of the Wnt/β-catenin signaling pathway during viral infection has been reported. In this study, we examined the effect of modulating Wnt/β-catenin signaling during influenza virus infection. The activation of the Wnt/β-catenin pathway by Wnt3a increased influenza virus mRNA and virus production in in vitro in mouse lung epithelial E10 cells and mRNA expresson of influenza virus genes in vivo in the lungs of mice infected with influenza virus A/Puerto Rico/8/34. However, the inhibition of Wnt/β-catenin signaling by iCRT14 reduced virus titer and viral gene expression in human lung epithelial A549 cells and viral replication in primary mouse alveolar epithelial cells infected with different influenza virus strains. Knockdown of β-catenin also reduced viral protein expression and virus production. iCRT14 acts at the early stage of virus replication. Treatment with iCRT14 inhibited the expression of the viral genes (vRNA, cRNA and mRNA) evaluated in this study. The intraperitoneal administration of iCRT14 reduced viral load, improved clinical signs, and partially protected mice from influenza virus infection.",2018 Jan 11,"['More, Sunil', 'Yang, Xiaoyun', 'Zhu, Zhengyu', 'Bamunuarachchi, Gayan', 'Guo, Yujie', 'Huang, Chaoqun', 'Bailey, Keith', 'Metcalf, Jordan P.', 'Liu, Lin']",PLoS One,,,True
d98b22c96490966661c90f9c892c717545c5f8fd,PMC,Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1006778,PMC5764453,29324904,CC BY,"A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus of serious public health concern. EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children. Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options. Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system. Meta-analysis with previously published proteomics studies in neuroblastoma or muscle cell lines revealed minimal overlapping which suggests unique host-pathogen interactions in NSC-34 cells. Among the candidate proteins, we focused our attention on prohibitin (PHB), a protein that is involved in multiple cellular functions and the target of anti-cancer drug Rocaglamide (Roc-A). We demonstrated that cell surface-expressed PHB is involved in EV71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication. Furthermore, Roc-A treatment of EV71-infected neuronal cells reduced significantly virus yields. However, the inhibitory effect of Roc-A on PHB in NSC-34 cells was not through blocking the CRAF/MEK/ERK pathway as previously reported. Instead, Roc-A treated NSC-34 cells had lower mitochondria-associated PHB and lower ATP levels that correlated with impaired mitochondria integrity. In vivo, EV71-infected mice treated with Roc-A survived longer than the vehicle-treated animals and had significantly lower virus loads in their spinal cord and brain, whereas virus titers in their limb muscles were comparable to controls. Together, this study uncovers PHB as the first host factor that is specifically involved in EV71 neuropathogenesis and a potential drug target to limit neurological complications.",2018 Jan 11,"['Too, Issac Horng Khit', 'Bonne, Isabelle', 'Tan, Eng Lee', 'Chu, Justin Jang Hann', 'Alonso, Sylvie']",PLoS Pathog,,,True
57f3f82db5e9b6de4c837801cafb013f70dc98cb,PMC,Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1006778,PMC5764453,29324904,CC BY,"A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus of serious public health concern. EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children. Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options. Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system. Meta-analysis with previously published proteomics studies in neuroblastoma or muscle cell lines revealed minimal overlapping which suggests unique host-pathogen interactions in NSC-34 cells. Among the candidate proteins, we focused our attention on prohibitin (PHB), a protein that is involved in multiple cellular functions and the target of anti-cancer drug Rocaglamide (Roc-A). We demonstrated that cell surface-expressed PHB is involved in EV71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication. Furthermore, Roc-A treatment of EV71-infected neuronal cells reduced significantly virus yields. However, the inhibitory effect of Roc-A on PHB in NSC-34 cells was not through blocking the CRAF/MEK/ERK pathway as previously reported. Instead, Roc-A treated NSC-34 cells had lower mitochondria-associated PHB and lower ATP levels that correlated with impaired mitochondria integrity. In vivo, EV71-infected mice treated with Roc-A survived longer than the vehicle-treated animals and had significantly lower virus loads in their spinal cord and brain, whereas virus titers in their limb muscles were comparable to controls. Together, this study uncovers PHB as the first host factor that is specifically involved in EV71 neuropathogenesis and a potential drug target to limit neurological complications.",2018 Jan 11,"['Too, Issac Horng Khit', 'Bonne, Isabelle', 'Tan, Eng Lee', 'Chu, Justin Jang Hann', 'Alonso, Sylvie']",PLoS Pathog,,,False
4e19aff8362be848b67c7d8b6a72d00d2b8ae372,PMC,Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1006778,PMC5764453,29324904,CC BY,"A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus of serious public health concern. EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children. Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options. Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system. Meta-analysis with previously published proteomics studies in neuroblastoma or muscle cell lines revealed minimal overlapping which suggests unique host-pathogen interactions in NSC-34 cells. Among the candidate proteins, we focused our attention on prohibitin (PHB), a protein that is involved in multiple cellular functions and the target of anti-cancer drug Rocaglamide (Roc-A). We demonstrated that cell surface-expressed PHB is involved in EV71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication. Furthermore, Roc-A treatment of EV71-infected neuronal cells reduced significantly virus yields. However, the inhibitory effect of Roc-A on PHB in NSC-34 cells was not through blocking the CRAF/MEK/ERK pathway as previously reported. Instead, Roc-A treated NSC-34 cells had lower mitochondria-associated PHB and lower ATP levels that correlated with impaired mitochondria integrity. In vivo, EV71-infected mice treated with Roc-A survived longer than the vehicle-treated animals and had significantly lower virus loads in their spinal cord and brain, whereas virus titers in their limb muscles were comparable to controls. Together, this study uncovers PHB as the first host factor that is specifically involved in EV71 neuropathogenesis and a potential drug target to limit neurological complications.",2018 Jan 11,"['Too, Issac Horng Khit', 'Bonne, Isabelle', 'Tan, Eng Lee', 'Chu, Justin Jang Hann', 'Alonso, Sylvie']",PLoS Pathog,,,False
1d2fd9c1079d54ff150662a771d6f2d8d47bd0ac,PMC,Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1006778,PMC5764453,29324904,CC BY,"A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus of serious public health concern. EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children. Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options. Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system. Meta-analysis with previously published proteomics studies in neuroblastoma or muscle cell lines revealed minimal overlapping which suggests unique host-pathogen interactions in NSC-34 cells. Among the candidate proteins, we focused our attention on prohibitin (PHB), a protein that is involved in multiple cellular functions and the target of anti-cancer drug Rocaglamide (Roc-A). We demonstrated that cell surface-expressed PHB is involved in EV71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication. Furthermore, Roc-A treatment of EV71-infected neuronal cells reduced significantly virus yields. However, the inhibitory effect of Roc-A on PHB in NSC-34 cells was not through blocking the CRAF/MEK/ERK pathway as previously reported. Instead, Roc-A treated NSC-34 cells had lower mitochondria-associated PHB and lower ATP levels that correlated with impaired mitochondria integrity. In vivo, EV71-infected mice treated with Roc-A survived longer than the vehicle-treated animals and had significantly lower virus loads in their spinal cord and brain, whereas virus titers in their limb muscles were comparable to controls. Together, this study uncovers PHB as the first host factor that is specifically involved in EV71 neuropathogenesis and a potential drug target to limit neurological complications.",2018 Jan 11,"['Too, Issac Horng Khit', 'Bonne, Isabelle', 'Tan, Eng Lee', 'Chu, Justin Jang Hann', 'Alonso, Sylvie']",PLoS Pathog,,,False
26e609c167e6a4ce7ad71c9301f8ba1ac139fafb,PMC,Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1006778,PMC5764453,29324904,CC BY,"A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus of serious public health concern. EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children. Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options. Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system. Meta-analysis with previously published proteomics studies in neuroblastoma or muscle cell lines revealed minimal overlapping which suggests unique host-pathogen interactions in NSC-34 cells. Among the candidate proteins, we focused our attention on prohibitin (PHB), a protein that is involved in multiple cellular functions and the target of anti-cancer drug Rocaglamide (Roc-A). We demonstrated that cell surface-expressed PHB is involved in EV71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication. Furthermore, Roc-A treatment of EV71-infected neuronal cells reduced significantly virus yields. However, the inhibitory effect of Roc-A on PHB in NSC-34 cells was not through blocking the CRAF/MEK/ERK pathway as previously reported. Instead, Roc-A treated NSC-34 cells had lower mitochondria-associated PHB and lower ATP levels that correlated with impaired mitochondria integrity. In vivo, EV71-infected mice treated with Roc-A survived longer than the vehicle-treated animals and had significantly lower virus loads in their spinal cord and brain, whereas virus titers in their limb muscles were comparable to controls. Together, this study uncovers PHB as the first host factor that is specifically involved in EV71 neuropathogenesis and a potential drug target to limit neurological complications.",2018 Jan 11,"['Too, Issac Horng Khit', 'Bonne, Isabelle', 'Tan, Eng Lee', 'Chu, Justin Jang Hann', 'Alonso, Sylvie']",PLoS Pathog,,,False
4e03846c3048cb3333b02046199a2662122d12af,PMC,Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1006778,PMC5764453,29324904,CC BY,"A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus of serious public health concern. EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children. Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options. Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system. Meta-analysis with previously published proteomics studies in neuroblastoma or muscle cell lines revealed minimal overlapping which suggests unique host-pathogen interactions in NSC-34 cells. Among the candidate proteins, we focused our attention on prohibitin (PHB), a protein that is involved in multiple cellular functions and the target of anti-cancer drug Rocaglamide (Roc-A). We demonstrated that cell surface-expressed PHB is involved in EV71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication. Furthermore, Roc-A treatment of EV71-infected neuronal cells reduced significantly virus yields. However, the inhibitory effect of Roc-A on PHB in NSC-34 cells was not through blocking the CRAF/MEK/ERK pathway as previously reported. Instead, Roc-A treated NSC-34 cells had lower mitochondria-associated PHB and lower ATP levels that correlated with impaired mitochondria integrity. In vivo, EV71-infected mice treated with Roc-A survived longer than the vehicle-treated animals and had significantly lower virus loads in their spinal cord and brain, whereas virus titers in their limb muscles were comparable to controls. Together, this study uncovers PHB as the first host factor that is specifically involved in EV71 neuropathogenesis and a potential drug target to limit neurological complications.",2018 Jan 11,"['Too, Issac Horng Khit', 'Bonne, Isabelle', 'Tan, Eng Lee', 'Chu, Justin Jang Hann', 'Alonso, Sylvie']",PLoS Pathog,,,False
94d14e94a43356fa0444653a907fc81b3d20246f,PMC,Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1006778,PMC5764453,29324904,CC BY,"A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus of serious public health concern. EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children. Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options. Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system. Meta-analysis with previously published proteomics studies in neuroblastoma or muscle cell lines revealed minimal overlapping which suggests unique host-pathogen interactions in NSC-34 cells. Among the candidate proteins, we focused our attention on prohibitin (PHB), a protein that is involved in multiple cellular functions and the target of anti-cancer drug Rocaglamide (Roc-A). We demonstrated that cell surface-expressed PHB is involved in EV71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication. Furthermore, Roc-A treatment of EV71-infected neuronal cells reduced significantly virus yields. However, the inhibitory effect of Roc-A on PHB in NSC-34 cells was not through blocking the CRAF/MEK/ERK pathway as previously reported. Instead, Roc-A treated NSC-34 cells had lower mitochondria-associated PHB and lower ATP levels that correlated with impaired mitochondria integrity. In vivo, EV71-infected mice treated with Roc-A survived longer than the vehicle-treated animals and had significantly lower virus loads in their spinal cord and brain, whereas virus titers in their limb muscles were comparable to controls. Together, this study uncovers PHB as the first host factor that is specifically involved in EV71 neuropathogenesis and a potential drug target to limit neurological complications.",2018 Jan 11,"['Too, Issac Horng Khit', 'Bonne, Isabelle', 'Tan, Eng Lee', 'Chu, Justin Jang Hann', 'Alonso, Sylvie']",PLoS Pathog,,,False
0df473dd89910a6ed2faaf2337b0ca1208d35d16,PMC,Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1006778,PMC5764453,29324904,CC BY,"A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus of serious public health concern. EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children. Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options. Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system. Meta-analysis with previously published proteomics studies in neuroblastoma or muscle cell lines revealed minimal overlapping which suggests unique host-pathogen interactions in NSC-34 cells. Among the candidate proteins, we focused our attention on prohibitin (PHB), a protein that is involved in multiple cellular functions and the target of anti-cancer drug Rocaglamide (Roc-A). We demonstrated that cell surface-expressed PHB is involved in EV71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication. Furthermore, Roc-A treatment of EV71-infected neuronal cells reduced significantly virus yields. However, the inhibitory effect of Roc-A on PHB in NSC-34 cells was not through blocking the CRAF/MEK/ERK pathway as previously reported. Instead, Roc-A treated NSC-34 cells had lower mitochondria-associated PHB and lower ATP levels that correlated with impaired mitochondria integrity. In vivo, EV71-infected mice treated with Roc-A survived longer than the vehicle-treated animals and had significantly lower virus loads in their spinal cord and brain, whereas virus titers in their limb muscles were comparable to controls. Together, this study uncovers PHB as the first host factor that is specifically involved in EV71 neuropathogenesis and a potential drug target to limit neurological complications.",2018 Jan 11,"['Too, Issac Horng Khit', 'Bonne, Isabelle', 'Tan, Eng Lee', 'Chu, Justin Jang Hann', 'Alonso, Sylvie']",PLoS Pathog,,,False
ed30d782f779b25db851365c7a93ae1d998faf1b,PMC,Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1006778,PMC5764453,29324904,CC BY,"A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus of serious public health concern. EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children. Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options. Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system. Meta-analysis with previously published proteomics studies in neuroblastoma or muscle cell lines revealed minimal overlapping which suggests unique host-pathogen interactions in NSC-34 cells. Among the candidate proteins, we focused our attention on prohibitin (PHB), a protein that is involved in multiple cellular functions and the target of anti-cancer drug Rocaglamide (Roc-A). We demonstrated that cell surface-expressed PHB is involved in EV71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication. Furthermore, Roc-A treatment of EV71-infected neuronal cells reduced significantly virus yields. However, the inhibitory effect of Roc-A on PHB in NSC-34 cells was not through blocking the CRAF/MEK/ERK pathway as previously reported. Instead, Roc-A treated NSC-34 cells had lower mitochondria-associated PHB and lower ATP levels that correlated with impaired mitochondria integrity. In vivo, EV71-infected mice treated with Roc-A survived longer than the vehicle-treated animals and had significantly lower virus loads in their spinal cord and brain, whereas virus titers in their limb muscles were comparable to controls. Together, this study uncovers PHB as the first host factor that is specifically involved in EV71 neuropathogenesis and a potential drug target to limit neurological complications.",2018 Jan 11,"['Too, Issac Horng Khit', 'Bonne, Isabelle', 'Tan, Eng Lee', 'Chu, Justin Jang Hann', 'Alonso, Sylvie']",PLoS Pathog,,,False
d15dfd546e238b29cacf7f28b83eb1cdb98f6ca8,PMC,Human complement receptor type 1 (CR1) protein levels and genetic variants in chronic Chagas Disease,http://dx.doi.org/10.1038/s41598-017-18937-z,PMC5765048,29323238,CC BY,"Complement is an essential element in both innate and acquired immunity contributing to the immunopathogenesis of many disorders, including Chagas Disease (CD). Human complement receptor 1 (CR1) plays a role in the clearance of complement opsonized molecules and may facilitate the entry of pathogens into host cells. Distinct CR1 exon 29 variants have been found associated with CR1 expression levels, increased susceptibility and pathophysiology of several diseases. In this study, CR1 plasma levels were assessed by ELISA and CR1 variants in exon 29 by sequencing in a Brazilian cohort of 232 chronic CD patients and 104 healthy controls. CR1 levels were significantly decreased in CD patients compared to controls (p < 0.0001). The CR1 rs1704660G, rs17047661G and rs6691117G variants were significantly associated with CD and in high linkage disequilibrium. The CR1*AGAGTG haplotype was associated with T. cruzi infection (p = 0.035, OR 3.99, CI 1.1-14.15) whereas CR1*AGGGTG was related to the risk of chagasic cardiomyopathy (p = 0.028, OR 12.15, CI 1.13-113). This is the first study that provides insights on the role of CR1 in development and clinical presentation of chronic CD.",2018 Jan 11,"['Sandri, Thaisa Lucas', 'Lidani, Kárita Cláudia Freitas', 'Andrade, Fabiana Antunes', 'Meyer, Christian G.', 'Kremsner, Peter G.', 'de Messias-Reason, Iara J.', 'Velavan, Thirumalaisamy P.']",Sci Rep,,,True
3a39684ab2bd22b39597a985ed3c57794a941a82,PMC,Haemophilus is overrepresented in the nasopharynx of infants hospitalized with RSV infection and associated with increased viral load and enhanced mucosal CXCL8 responses,http://dx.doi.org/10.1186/s40168-017-0395-y,PMC5765694,29325581,CC BY,"BACKGROUND: While almost all infants are infected with respiratory syncytial virus (RSV) before the age of 2 years, only a small percentage develops severe disease. Previous studies suggest that the nasopharyngeal microbiome affects disease development. We therefore studied the effect of the nasopharyngeal microbiome on viral load and mucosal cytokine responses, two important factors influencing the pathophysiology of RSV disease. To determine the relation between (i) the microbiome of the upper respiratory tract, (ii) viral load, and (iii) host mucosal inflammation during an RSV infection, nasopharyngeal microbiota profiles of RSV infected infants (< 6 months) with different levels of disease severity and age-matched healthy controls were determined by 16S rRNA marker gene sequencing. The viral load was measured using qPCR. Nasopharyngeal CCL5, CXCL10, MMP9, IL6, and CXCL8 levels were determined with ELISA. RESULTS: Viral load in nasopharyngeal aspirates of patients associates significantly to total nasopharyngeal microbiota composition. Healthy infants (n = 21) and RSV patients (n = 54) display very distinct microbial patterns, primarily characterized by a loss in commensals like Veillonella and overrepresentation of opportunistic organisms like Haemophilus and Achromobacter in RSV-infected individuals. Furthermore, nasopharyngeal microbiota profiles are significantly different based on CXCL8 levels. CXCL8 is a chemokine that was previously found to be indicative for disease severity and for which we find Haemophilus abundance as the strongest predictor for CXCL8 levels. CONCLUSIONS: The nasopharyngeal microbiota in young infants with RSV infection is marked by an overrepresentation of the genus Haemophilus. We present that this bacterium is associated with viral load and mucosal CXCL8 responses, both which are involved in RSV disease pathogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40168-017-0395-y) contains supplementary material, which is available to authorized users.",2018 Jan 11,"['Ederveen, Thomas H. A.', 'Ferwerda, Gerben', 'Ahout, Inge M.', 'Vissers, Marloes', 'de Groot, Ronald', 'Boekhorst, Jos', 'Timmerman, Harro M.', 'Huynen, Martijn A.', 'van Hijum, Sacha A. F. T.', 'de Jonge, Marien I.']",Microbiome,,,True
87ea5f33f033c465a124321613ad36f96a560eba,PMC,Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection,http://dx.doi.org/10.1371/journal.ppat.1006810,PMC5766251,29293660,CC BY,"Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.",2018 Jan 2,"['Schmidt, Megan E.', 'Knudson, Cory J.', 'Hartwig, Stacey M.', 'Pewe, Lecia L.', 'Meyerholz, David K.', 'Langlois, Ryan A.', 'Harty, John T.', 'Varga, Steven M.']",PLoS Pathog,,,True
a6f883c29df7f1bb38d472c3f1f7d5647935a077,PMC,Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection,http://dx.doi.org/10.1371/journal.ppat.1006810,PMC5766251,29293660,CC BY,"Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.",2018 Jan 2,"['Schmidt, Megan E.', 'Knudson, Cory J.', 'Hartwig, Stacey M.', 'Pewe, Lecia L.', 'Meyerholz, David K.', 'Langlois, Ryan A.', 'Harty, John T.', 'Varga, Steven M.']",PLoS Pathog,,,False
24750914323d00b08ca9ac2d2c58353bd88526fb,PMC,Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection,http://dx.doi.org/10.1371/journal.ppat.1006810,PMC5766251,29293660,CC BY,"Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.",2018 Jan 2,"['Schmidt, Megan E.', 'Knudson, Cory J.', 'Hartwig, Stacey M.', 'Pewe, Lecia L.', 'Meyerholz, David K.', 'Langlois, Ryan A.', 'Harty, John T.', 'Varga, Steven M.']",PLoS Pathog,,,False
01b6789de33bebc284713c22c90cb11d33c2a029,PMC,Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection,http://dx.doi.org/10.1371/journal.ppat.1006810,PMC5766251,29293660,CC BY,"Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.",2018 Jan 2,"['Schmidt, Megan E.', 'Knudson, Cory J.', 'Hartwig, Stacey M.', 'Pewe, Lecia L.', 'Meyerholz, David K.', 'Langlois, Ryan A.', 'Harty, John T.', 'Varga, Steven M.']",PLoS Pathog,,,False
91bdeee10d876369be3c7e80ea69c9aedfac805e,PMC,Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection,http://dx.doi.org/10.1371/journal.ppat.1006810,PMC5766251,29293660,CC BY,"Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.",2018 Jan 2,"['Schmidt, Megan E.', 'Knudson, Cory J.', 'Hartwig, Stacey M.', 'Pewe, Lecia L.', 'Meyerholz, David K.', 'Langlois, Ryan A.', 'Harty, John T.', 'Varga, Steven M.']",PLoS Pathog,,,False
bd788a8d8076040ff66825818479d21cfae5929e,PMC,Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection,http://dx.doi.org/10.1371/journal.ppat.1006810,PMC5766251,29293660,CC BY,"Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.",2018 Jan 2,"['Schmidt, Megan E.', 'Knudson, Cory J.', 'Hartwig, Stacey M.', 'Pewe, Lecia L.', 'Meyerholz, David K.', 'Langlois, Ryan A.', 'Harty, John T.', 'Varga, Steven M.']",PLoS Pathog,,,False
33d897d79842b966e73fce74539cc689e2dcc196,PMC,Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection,http://dx.doi.org/10.1371/journal.ppat.1006810,PMC5766251,29293660,CC BY,"Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.",2018 Jan 2,"['Schmidt, Megan E.', 'Knudson, Cory J.', 'Hartwig, Stacey M.', 'Pewe, Lecia L.', 'Meyerholz, David K.', 'Langlois, Ryan A.', 'Harty, John T.', 'Varga, Steven M.']",PLoS Pathog,,,False
8ac4abed26e7e390780d3056f618c787020b24b7,PMC,Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection,http://dx.doi.org/10.1371/journal.ppat.1006810,PMC5766251,29293660,CC BY,"Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.",2018 Jan 2,"['Schmidt, Megan E.', 'Knudson, Cory J.', 'Hartwig, Stacey M.', 'Pewe, Lecia L.', 'Meyerholz, David K.', 'Langlois, Ryan A.', 'Harty, John T.', 'Varga, Steven M.']",PLoS Pathog,,,False
d887e66d8530baa88f86874d68c0b7196509831b,PMC,Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection,http://dx.doi.org/10.1371/journal.ppat.1006810,PMC5766251,29293660,CC BY,"Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.",2018 Jan 2,"['Schmidt, Megan E.', 'Knudson, Cory J.', 'Hartwig, Stacey M.', 'Pewe, Lecia L.', 'Meyerholz, David K.', 'Langlois, Ryan A.', 'Harty, John T.', 'Varga, Steven M.']",PLoS Pathog,,,False
473da5fb85616f6b7758f953ef3ad172a4a290c4,PMC,Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection,http://dx.doi.org/10.1371/journal.ppat.1006810,PMC5766251,29293660,CC BY,"Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.",2018 Jan 2,"['Schmidt, Megan E.', 'Knudson, Cory J.', 'Hartwig, Stacey M.', 'Pewe, Lecia L.', 'Meyerholz, David K.', 'Langlois, Ryan A.', 'Harty, John T.', 'Varga, Steven M.']",PLoS Pathog,,,False
2d0aef433731b00a793ce7e1778439676dad7a59,PMC,Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection,http://dx.doi.org/10.1371/journal.ppat.1006810,PMC5766251,29293660,CC BY,"Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.",2018 Jan 2,"['Schmidt, Megan E.', 'Knudson, Cory J.', 'Hartwig, Stacey M.', 'Pewe, Lecia L.', 'Meyerholz, David K.', 'Langlois, Ryan A.', 'Harty, John T.', 'Varga, Steven M.']",PLoS Pathog,,,False
85079729777ebf9bf43b0bf1253888a7527f7e33,PMC,Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection,http://dx.doi.org/10.1371/journal.ppat.1006810,PMC5766251,29293660,CC BY,"Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.",2018 Jan 2,"['Schmidt, Megan E.', 'Knudson, Cory J.', 'Hartwig, Stacey M.', 'Pewe, Lecia L.', 'Meyerholz, David K.', 'Langlois, Ryan A.', 'Harty, John T.', 'Varga, Steven M.']",PLoS Pathog,,,False
82a4da59f4d42fdff77fabeddee882d973e48c09,PMC,Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection,http://dx.doi.org/10.1371/journal.ppat.1006810,PMC5766251,29293660,CC BY,"Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.",2018 Jan 2,"['Schmidt, Megan E.', 'Knudson, Cory J.', 'Hartwig, Stacey M.', 'Pewe, Lecia L.', 'Meyerholz, David K.', 'Langlois, Ryan A.', 'Harty, John T.', 'Varga, Steven M.']",PLoS Pathog,,,False
dd35470606b07447c3f3a4e8688168659d4d9023,PMC,Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection,http://dx.doi.org/10.1371/journal.ppat.1006810,PMC5766251,29293660,CC BY,"Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.",2018 Jan 2,"['Schmidt, Megan E.', 'Knudson, Cory J.', 'Hartwig, Stacey M.', 'Pewe, Lecia L.', 'Meyerholz, David K.', 'Langlois, Ryan A.', 'Harty, John T.', 'Varga, Steven M.']",PLoS Pathog,,,False
52d4bf773931d4aaef87f60b1b060e93aa456fba,PMC,Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection,http://dx.doi.org/10.1371/journal.ppat.1006810,PMC5766251,29293660,CC BY,"Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.",2018 Jan 2,"['Schmidt, Megan E.', 'Knudson, Cory J.', 'Hartwig, Stacey M.', 'Pewe, Lecia L.', 'Meyerholz, David K.', 'Langlois, Ryan A.', 'Harty, John T.', 'Varga, Steven M.']",PLoS Pathog,,,False
3be0bd1914203f4536b93862e93434e84e531335,PMC,Excess of Mortality in Adults and Elderly and Circulation of Subtypes of Influenza Virus in Southern Brazil,http://dx.doi.org/10.3389/fimmu.2017.01903,PMC5767013,29375560,CC BY,"PURPOSE: In the elderly population, the influenza infection and its clinical complications are important causes of hospitalization and death, particularly, in longer-lived age. The objective of this study is to analyze the impact of influenza virus circulation on mortality in the elderly and adults, in years with different predominant virus strains. METHODS: We performed a time trend study to evaluated excess of mortality for pneumonia and influenza, respiratory disease, and all-causes in southern region of Brazil, from 2002 to 2015. After considering other models, we opted for Serfling regression. Excess of death rates per 100,000 inhabitants were analyzed in specific age groups (24–59, 60–69, 70–79, ≥80 years) and by year of occurrence. Mortality information were taken from Brazilian Mortality Information System and etiological data were accessed in Sentinel Virological Surveillance database, getting the weekly positivity of the immunofluorescence tests for influenza A (H1N1, H3N2), and B. RESULTS: In southern Brazil, there is an evident seasonal pattern of all death outcomes among different age groups in the dry and cold season (April–September). The highest excess mortality rates occurs among older, particularly in years of circulation of influenza AH3N2, especially among people ≥80 years, in 2003 and 2007—years of great severity of influenza activity. After 2009, with the introduction of the pandemic influenza AH1N1, we observed a lower impact on the mortality of the elderly compared to <60 years. DISCUSSION: A cross reactivity antibody response from past exposure probably provided protection against disease in the elderly. Despite not controlling for comorbidities, climate, and vaccination, for the >70 years, ratio of respiratory diseases excess mortality rates between AH1N1 (2009) and severe year of H3N2 (2007) shows protection in the pandemic year and great vulnerability during AH3N2 virus predominance. CONCLUSION: The reduced immune response to infection, and to vaccination, and presence of comorbidities recommend a special attention to this age group in Brazil. Besides medical assistance, the timeliness of vaccine campaigns, its composition, and etiological surveillance of respiratory diseases are some of the preventive and public health measures.",2018 Jan 8,"['Freitas, André Ricardo Ribas', 'Donalisio, Maria Rita']",Front Immunol,,,True
fef1b7df61f24d4ef20baa830f7b89ad75495e40,PMC,A large-scale study of a poultry trading network in Bangladesh: implications for control and surveillance of avian influenza viruses,http://dx.doi.org/10.1186/s12917-018-1331-5,PMC5767022,29329534,CC BY,"BACKGROUND: Since its first report in 2007, avian influenza (AI) has been endemic in Bangladesh. While live poultry marketing is widespread throughout the country and known to influence AI dissemination and persistence, trading patterns have not been described. The aim of this study is to assess poultry trading practices and features of the poultry trading networks which could promote AI spread, and their potential implications for disease control and surveillance. Data on poultry trading practices was collected from 849 poultry traders during a cross-sectional survey in 138 live bird markets (LBMs) across 17 different districts of Bangladesh. The quantity and origins of traded poultry were assessed for each poultry type in surveyed LBMs. The network of contacts between farms and LBMs resulting from commercial movements of live poultry was constructed to assess its connectivity and to identify the key premises influencing it. RESULTS: Poultry trading practices varied according to the size of the LBMs and to the type of poultry traded. Industrial broiler chickens, the most commonly traded poultry, were generally sold in LBMs close to their production areas, whereas ducks and backyard chickens were moved over longer distances, and their transport involved several intermediates. The poultry trading network composed of 445 nodes (73.2% were LBMs) was highly connected and disassortative. However, the removal of only 5.6% of the nodes (25 LBMs with the highest betweenness scores), reduced the network’s connectedness, and the maximum size of output and input domains by more than 50%. CONCLUSIONS: Poultry types need to be discriminated in order to understand the way in which poultry trading networks are shaped, and the level of risk of disease spread that these networks may promote. Knowledge of the network structure could be used to target control and surveillance interventions to a small number of LBMs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1331-5) contains supplementary material, which is available to authorized users.",2018 Jan 12,"['Moyen, N.', 'Ahmed, G.', 'Gupta, S.', 'Tenzin, T.', 'Khan, R.', 'Khan, T.', 'Debnath, N.', 'Yamage, M.', 'Pfeiffer, D.U.', 'Fournie, G.']",BMC Vet Res,,,True
0bcb08a254f823c2008e13dfa4eea37de9ebae91,PMC,Correction to: Detection and full genome characterization of two beta CoV viruses related to Middle East respiratory syndrome from bats in Italy,http://dx.doi.org/10.1186/s12985-018-0921-y,PMC5767041,29329554,CC BY,,2018 Jan 12,"['Moreno, Ana', 'Lelli, Davide', 'De Sabato, Luca', 'Zaccaria, Guendalina', 'Boni, Arianna', 'Sozzi, Enrica', 'Prosperi, Alice', 'Lavazza, Antonio', 'Cella, Eleonora', 'Castrucci, Maria Rita', 'Ciccozzi, Massimo', 'Vaccari, Gabriele']",Virol J,,,False
a79847f406c9f694222cc18a1ffd04dbc0c06d08,PMC,Interactions of Alphavirus nsP3 Protein with Host Proteins,http://dx.doi.org/10.3389/fmicb.2017.02652,PMC5767282,29375517,CC BY,"Alphaviruses are members of the Togaviridae family and are grouped into two categories: arthritogenic and encephalitic. Arthritogenic alphavirus infections, as the name implies, are associated with arthritic outcomes while encephalitic alphavirus infections can lead to encephalitic outcomes in the infected host. Of the non-structural proteins (nsPs) that the viruses code for, nsP3 is the least understood in terms of function. Alphavirus nsP3s are characterized by regions with significantly conserved domain structure along with regions of high variability. Interactions of nsP3 with several host proteins have been documented including, stress granule-related proteins, dead box proteins, heat shock proteins, and kinases. In some cases, in addition to the interaction, requirement of the interaction to support infection has been demonstrated. An understanding of the proteomic network of nsP3 and the mechanisms by which these interactions support the establishment of a productive infection would make alphavirus nsP3 an interesting target for design of effective medical countermeasures.",2018 Jan 9,"['Lark, Tyler', 'Keck, Forrest', 'Narayanan, Aarthi']",Front Microbiol,,,True
7b6d913cc102a8e122847122f07ee230aa0c3d78,PMC,FastViromeExplorer: a pipeline for virus and phage identification and abundance profiling in metagenomics data,http://dx.doi.org/10.7717/peerj.4227,PMC5768174,29340239,CC BY,"With the increase in the availability of metagenomic data generated by next generation sequencing, there is an urgent need for fast and accurate tools for identifying viruses in host-associated and environmental samples. In this paper, we developed a stand-alone pipeline called FastViromeExplorer for the detection and abundance quantification of viruses and phages in large metagenomic datasets by performing rapid searches of virus and phage sequence databases. Both simulated and real data from human microbiome and ocean environmental samples are used to validate FastViromeExplorer as a reliable tool to quickly and accurately identify viruses and their abundances in large datasets.",2018 Jan 12,"['Tithi, Saima Sultana', 'Aylward, Frank O.', 'Jensen, Roderick V.', 'Zhang, Liqing']",PeerJ,,,True
0276133204889a33c9fcc887c7034fa8b78c9ce9,PMC,FastViromeExplorer: a pipeline for virus and phage identification and abundance profiling in metagenomics data,http://dx.doi.org/10.7717/peerj.4227,PMC5768174,29340239,CC BY,"With the increase in the availability of metagenomic data generated by next generation sequencing, there is an urgent need for fast and accurate tools for identifying viruses in host-associated and environmental samples. In this paper, we developed a stand-alone pipeline called FastViromeExplorer for the detection and abundance quantification of viruses and phages in large metagenomic datasets by performing rapid searches of virus and phage sequence databases. Both simulated and real data from human microbiome and ocean environmental samples are used to validate FastViromeExplorer as a reliable tool to quickly and accurately identify viruses and their abundances in large datasets.",2018 Jan 12,"['Tithi, Saima Sultana', 'Aylward, Frank O.', 'Jensen, Roderick V.', 'Zhang, Liqing']",PeerJ,,,False
7c9124f96076006b57906b10d2add5b7c7928ce0,PMC,Extracorporeal membrane oxygenation for severe Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1186/s13613-017-0350-x,PMC5768582,29330690,CC BY,"BACKGROUND: Middle East respiratory syndrome (MERS) is caused by a coronavirus (MERS‐CoV) and is characterized by hypoxemic respiratory failure. The objective of this study is to compare the outcomes of MERS-CoV patients before and after the availability of extracorporeal membrane oxygenation (ECMO) as a rescue therapy in severely hypoxemic patients who failed conventional strategies. METHODS: We collected data retrospectively on MERS-CoV patients with refractory respiratory failure from April 2014 to December 2015 in 5 intensive care units (ICUs) in Saudi Arabia. Patients were classified into two groups: ECMO versus conventional therapy. Our primary outcome was in-hospital mortality; secondary outcomes included ICU and hospital length of stay. RESULTS: Thirty-five patients were included; 17 received ECMO and 18 received conventional therapy. Both groups had similar baseline characteristics. The ECMO group had lower in-hospital mortality (65 vs. 100%, P = 0.02), longer ICU stay (median 25 vs. 8 days, respectively, P < 0.01), and similar hospital stay (median 41 vs. 31 days, P = 0.421). In addition, patients in the ECMO group had better PaO2/FiO2 at days 7 and 14 of admission to the ICU (124 vs. 63, and 138 vs. 36, P < 0.05), and less use of norepinephrine at days 1 and 14 (29 vs. 80%; and 36 vs. 93%, P < 0.05). CONCLUSIONS: ECMO use, as a rescue therapy, was associated with lower mortality in MERS patients with refractory hypoxemia. The results of this, largest to date, support the use of ECMO as a rescue therapy in patients with severe MERS-CoV.",2018 Jan 10,"['Alshahrani, Mohammed S.', 'Sindi, Anees', 'Alshamsi, Fayez', 'Al-Omari, Awad', 'El Tahan, Mohamed', 'Alahmadi, Bayan', 'Zein, Ahmed', 'Khatani, Naif', 'Al-Hameed, Fahad', 'Alamri, Sultan', 'Abdelzaher, Mohammed', 'Alghamdi, Amenah', 'Alfousan, Faisal', 'Tash, Adel', 'Tashkandi, Wail', 'Alraddadi, Rajaa', 'Lewis, Kim', 'Badawee, Mohammed', 'Arabi, Yaseen M.', 'Fan, Eddy', 'Alhazzani, Waleed']",Ann Intensive Care,,,True
f22712c761c7afae14306fbfda6eabc2140a8eaf,PMC,Characterizing the dynamics underlying global spread of epidemics,http://dx.doi.org/10.1038/s41467-017-02344-z,PMC5768765,29335536,CC BY,"Over the past few decades, global metapopulation epidemic simulations built with worldwide air-transportation data have been the main tool for studying how epidemics spread from the origin to other parts of the world (e.g., for pandemic influenza, SARS, and Ebola). However, it remains unclear how disease epidemiology and the air-transportation network structure determine epidemic arrivals for different populations around the globe. Here, we fill this knowledge gap by developing and validating an analytical framework that requires only basic analytics from stochastic processes. We apply this framework retrospectively to the 2009 influenza pandemic and 2014 Ebola epidemic to show that key epidemic parameters could be robustly estimated in real-time from public data on local and global spread at very low computational cost. Our framework not only elucidates the dynamics underlying global spread of epidemics but also advances our capability in nowcasting and forecasting epidemics.",2018 Jan 15,"['Wang, Lin', 'Wu, Joseph T.']",Nat Commun,,,False
10cde393daca9e70454218e2721e46bce76eebba,PMC,Characterizing the dynamics underlying global spread of epidemics,http://dx.doi.org/10.1038/s41467-017-02344-z,PMC5768765,29335536,CC BY,"Over the past few decades, global metapopulation epidemic simulations built with worldwide air-transportation data have been the main tool for studying how epidemics spread from the origin to other parts of the world (e.g., for pandemic influenza, SARS, and Ebola). However, it remains unclear how disease epidemiology and the air-transportation network structure determine epidemic arrivals for different populations around the globe. Here, we fill this knowledge gap by developing and validating an analytical framework that requires only basic analytics from stochastic processes. We apply this framework retrospectively to the 2009 influenza pandemic and 2014 Ebola epidemic to show that key epidemic parameters could be robustly estimated in real-time from public data on local and global spread at very low computational cost. Our framework not only elucidates the dynamics underlying global spread of epidemics but also advances our capability in nowcasting and forecasting epidemics.",2018 Jan 15,"['Wang, Lin', 'Wu, Joseph T.']",Nat Commun,,,False
fed39ba33ece570bf3f7e8879cf448bf93cd069e,PMC,Characterizing the dynamics underlying global spread of epidemics,http://dx.doi.org/10.1038/s41467-017-02344-z,PMC5768765,29335536,CC BY,"Over the past few decades, global metapopulation epidemic simulations built with worldwide air-transportation data have been the main tool for studying how epidemics spread from the origin to other parts of the world (e.g., for pandemic influenza, SARS, and Ebola). However, it remains unclear how disease epidemiology and the air-transportation network structure determine epidemic arrivals for different populations around the globe. Here, we fill this knowledge gap by developing and validating an analytical framework that requires only basic analytics from stochastic processes. We apply this framework retrospectively to the 2009 influenza pandemic and 2014 Ebola epidemic to show that key epidemic parameters could be robustly estimated in real-time from public data on local and global spread at very low computational cost. Our framework not only elucidates the dynamics underlying global spread of epidemics but also advances our capability in nowcasting and forecasting epidemics.",2018 Jan 15,"['Wang, Lin', 'Wu, Joseph T.']",Nat Commun,,,True
70d09fb4f3c4d083724543f4d885d904ea69a5d0,PMC,Event based surveillance of Middle East Respiratory Syndrome Coronavirus (MERS- CoV) in Bangladesh among pilgrims and travelers from the Middle East: An update for the period 2013–2016,http://dx.doi.org/10.1371/journal.pone.0189914,PMC5770030,29337997,CC BY,"INTRODUCTION: Every year around 150,000 pilgrims from Bangladesh perform Umrah and Hajj. Emergence and continuous reporting of MERS-CoV infection in Saudi Arabia emphasize the need for surveillance of MERS-CoV in returning pilgrims or travelers from the Middle East and capacity building of health care providers for disease containment. The Institute of Epidemiology, Disease Control & Research (IEDCR) under the Bangladesh Ministry of Health and Family welfare (MoHFW), is responsible for MERS-CoV screening of pilgrims/ travelers returning from the Middle East with respiratory illness as part of its outbreak investigation and surveillance activities. METHODS: Bangladeshi travelers/pilgrims who returned from the Middle East and presented with fever and respiratory symptoms were studied over the period from October 2013 to June 2016. Patients with respiratory symptoms that fulfilled the WHO MERS-CoV case algorithm were tested for MERS-CoV and other respiratory tract viruses. Beside surveillance, case recognition training was conducted at multiple levels of health care facilities across the country in support of early detection and containment of the disease. RESULTS: Eighty one suspected cases tested by real time PCR resulted in zero detection of MERS-CoV infection. Viral etiology detected in 29.6% of the cases was predominantly influenza A (H1N1 and H3N2), and influenza B infection (22%). Peak testing occurred mostly following the annual Hajj season. CONCLUSIONS: Respiratory tract infections in travelers/pilgrims returning to Bangladesh from the Middle East are mainly due to influenza A and influenza B. Though MERS-CoV was not detected in the 81 patients tested, continuous screening and surveillance are essential for early detection of MERS-CoV infection and other respiratory pathogens to prevent transmissions in hospital settings and within communities. Awareness building among healthcare providers will help identify suspected cases.",2018 Jan 16,"['Muraduzzaman, A. K. M.', 'Khan, Manjur Hossain', 'Parveen, Rezina', 'Sultana, Sharmin', 'Alam, Ahmed Nawsher', 'Akram, Arifa', 'Rahman, Mahmudur', 'Shirin, Tahmina']",PLoS One,,,True
fe4829233859c2471b9aa99a1027a1fab44b153c,PMC,Glial- and Neuronal-Specific Expression of CCL5 mRNA in the Rat Brain,http://dx.doi.org/10.3389/fnana.2017.00137,PMC5770405,29375328,CC BY,"Chemokine (C-C motif) ligand 5 (CCL5) belongs to a group of chemokines that play a role in the peripheral immune system, mostly as chemoattractant molecules, and mediate tactile allodynia. In the central nervous system (CNS), CCL5 and its receptors have multiple functions, including promoting neuroinflammation, insulin signaling, neuromodulator of synaptic activity and neuroprotection against a variety of neurotoxins. Evidence has also suggested that this chemokine may regulate opioid response. The multifunctional profile of CCL5 might correlate with its ability to bind different chemokine receptors, as well as with its unique cellular expression. In this work, we have used fluorescence in situ hybridization combined with immunohistochemistry to examine the expression profile of CCL5 mRNA in the adult rat brain and provide evidence of its cellular localization. We have observed that the highest expression of CCL5 mRNA occurs in all major fiber tracts, including the corpus callosum, anterior commissure, and cerebral peduncle. In these tracts, CCL5 mRNA was localized in oligodendrocytes, astrocytes and microglia. Astrocytic and microglial expression was also evident in several brain areas including the cerebral cortex, caudate/putamen, hippocampus, and thalamus. Furthermore, using a specific neuronal marker, we observed CCL5 mRNA expression in discrete layers of the cortex and hippocampus. Interestingly, in the midbrain, CCL5 mRNA co-localized with tyrosine hydroxylase (TH) positive cells of the ventral tegmental area, suggesting that CCL5 might be expressed by a subset of dopaminergic neurons of the mesolimbic system. The expression of CCL5 mRNA and protein, together with its receptors, in selected brain cell populations proposes that this chemokine could be involved in neuronal/glial communication.",2018 Jan 12,"['Lanfranco, Maria Fe', 'Mocchetti, Italo', 'Burns, Mark P.', 'Villapol, Sonia']",Front Neuroanat,,,True
bb8030d58fcf70a3f77b3edb702ed8801f56cc0a,PMC,Transcriptome profiling of whitefly guts in response to Tomato yellow leaf curl virus infection,http://dx.doi.org/10.1186/s12985-018-0926-6,PMC5771010,29338737,CC BY,"BACKGROUND: Plant viruses in agricultural crops are of great concern worldwide, and over 75% of them are transmitted from infected to healthy plants by insect vectors. Tomato yellow leaf curl virus (TYLCV) is a begomovirus, which is the largest and most economically important group of plant viruses, transmitted by the whitefly Bemisia tabaci. The circulation of TYLCV in the insect involves complex insect-virus interactions, whereas the molecular mechanisms of these interactions remain ambiguous. The insect gut as a barrier for viral entry and dissemination is thought to regulate the vector specificity. However, due to its tiny size, information for the responses of whitefly gut to virus infection is limited. METHODS: We investigated the transcriptional response of the gut of B. tabaci Middle East-Asia Minor 1 species to TYLCV infection using Illumina sequencing. RESULTS: A total of 5207 differentially expressed genes (DEGs) between viruliferous and non-viruliferous whitefly guts were identified. Enrichment analyses showed that cargo receptor and ATP-binding cassette (ABC) transporters were enriched in DEGs, and might help the virus to cross gut barrier. TYLCV could perturb cell cycle and DNA repair as a possible result of its replication in the whitefly. Our data also demonstrated that TYLCV can activate whitefly defense responses, such as antimicrobial peptides. Meanwhile, a number of genes involved in intracellular signaling were activated by TYLCV infection. CONCLUSIONS: Our results reveal the complex insect-virus relationship in whitefly gut and provide substantial molecular information for the role of insect midguts in virus transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-0926-6) contains supplementary material, which is available to authorized users.",2018 Jan 16,"['Geng, Liang', 'Qian, Li-Xin', 'Shao, Ruo-Xuan', 'Liu, Yin-Quan', 'Liu, Shu-Sheng', 'Wang, Xiao-Wei']",Virol J,,,True
0fb489a4d557dce1e9db500c3f6d6eb6978dc087,PMC,Novel Immunoinformatics Approaches to Design Multi-epitope Subunit Vaccine for Malaria by Investigating Anopheles Salivary Protein,http://dx.doi.org/10.1038/s41598-018-19456-1,PMC5773588,29348555,CC BY,"Malaria fever has been pervasive for quite a while in tropical developing regions causing high morbidity and mortality. The causal organism is a protozoan parasite of genus Plasmodium which spreads to the human host by the bite of hitherto infected female Anopheles mosquito. In the course of biting, a salivary protein of Anopheles helps in blood feeding behavior and having the ability to elicit the host immune response. This study represents a series of immunoinformatics approaches to design multi-epitope subunit vaccine using Anopheles mosquito salivary proteins. Designed subunit vaccine was evaluated for its immunogenicity, allergenicity and physiochemical parameters. To enhance the stability of vaccine protein, disulfide engineering was performed in a region of high mobility. Codon adaptation and in silico cloning was also performed to ensure the higher expression of designed subunit vaccine in E. coli K12 expression system. Finally, molecular docking and simulation study was performed for the vaccine protein and TLR-4 receptor, to determine the binding free energy and complex stability. Moreover, the designed subunit vaccine was found to induce anti-salivary immunity which may have the ability to prevent the entry of Plasmodium sporozoites into the human host.",2018 Jan 18,"['Pandey, Rajan Kumar', 'Bhatt, Tarun Kumar', 'Prajapati, Vijay Kumar']",Sci Rep,,,False
d05db9cdccfa196d13b8eb58b09208937911d70e,PMC,Novel Immunoinformatics Approaches to Design Multi-epitope Subunit Vaccine for Malaria by Investigating Anopheles Salivary Protein,http://dx.doi.org/10.1038/s41598-018-19456-1,PMC5773588,29348555,CC BY,"Malaria fever has been pervasive for quite a while in tropical developing regions causing high morbidity and mortality. The causal organism is a protozoan parasite of genus Plasmodium which spreads to the human host by the bite of hitherto infected female Anopheles mosquito. In the course of biting, a salivary protein of Anopheles helps in blood feeding behavior and having the ability to elicit the host immune response. This study represents a series of immunoinformatics approaches to design multi-epitope subunit vaccine using Anopheles mosquito salivary proteins. Designed subunit vaccine was evaluated for its immunogenicity, allergenicity and physiochemical parameters. To enhance the stability of vaccine protein, disulfide engineering was performed in a region of high mobility. Codon adaptation and in silico cloning was also performed to ensure the higher expression of designed subunit vaccine in E. coli K12 expression system. Finally, molecular docking and simulation study was performed for the vaccine protein and TLR-4 receptor, to determine the binding free energy and complex stability. Moreover, the designed subunit vaccine was found to induce anti-salivary immunity which may have the ability to prevent the entry of Plasmodium sporozoites into the human host.",2018 Jan 18,"['Pandey, Rajan Kumar', 'Bhatt, Tarun Kumar', 'Prajapati, Vijay Kumar']",Sci Rep,,,True
d16f97626aabd7b5350d85d8cb07498bf2386a7e,PMC,Quantifying the Risk and Cost of Active Monitoring for Infectious Diseases,http://dx.doi.org/10.1038/s41598-018-19406-x,PMC5773605,29348656,CC BY,"During outbreaks of deadly emerging pathogens (e.g., Ebola, MERS-CoV) and bioterror threats (e.g., smallpox), actively monitoring potentially infected individuals aims to limit disease transmission and morbidity. Guidance issued by CDC on active monitoring was a cornerstone of its response to the West Africa Ebola outbreak. There are limited data on how to balance the costs and performance of this important public health activity. We present a framework that estimates the risks and costs of specific durations of active monitoring for pathogens of significant public health concern. We analyze data from New York City’s Ebola active monitoring program over a 16-month period in 2014–2016. For monitored individuals, we identified unique durations of active monitoring that minimize expected costs for those at “low (but not zero) risk” and “some or high risk”: 21 and 31 days, respectively. Extending our analysis to smallpox and MERS-CoV, we found that the optimal length of active monitoring relative to the median incubation period was reduced compared to Ebola due to less variable incubation periods. Active monitoring can save lives but is expensive. Resources can be most effectively allocated by using exposure-risk categories to modify the duration or intensity of active monitoring.",2018 Jan 18,"['Reich, Nicholas G.', 'Lessler, Justin', 'Varma, Jay K.', 'Vora, Neil M.']",Sci Rep,,,True
24f1d3b412c3e8fcbbd6807643cc193ef00b5ed8,PMC,Quantifying the Risk and Cost of Active Monitoring for Infectious Diseases,http://dx.doi.org/10.1038/s41598-018-19406-x,PMC5773605,29348656,CC BY,"During outbreaks of deadly emerging pathogens (e.g., Ebola, MERS-CoV) and bioterror threats (e.g., smallpox), actively monitoring potentially infected individuals aims to limit disease transmission and morbidity. Guidance issued by CDC on active monitoring was a cornerstone of its response to the West Africa Ebola outbreak. There are limited data on how to balance the costs and performance of this important public health activity. We present a framework that estimates the risks and costs of specific durations of active monitoring for pathogens of significant public health concern. We analyze data from New York City’s Ebola active monitoring program over a 16-month period in 2014–2016. For monitored individuals, we identified unique durations of active monitoring that minimize expected costs for those at “low (but not zero) risk” and “some or high risk”: 21 and 31 days, respectively. Extending our analysis to smallpox and MERS-CoV, we found that the optimal length of active monitoring relative to the median incubation period was reduced compared to Ebola due to less variable incubation periods. Active monitoring can save lives but is expensive. Resources can be most effectively allocated by using exposure-risk categories to modify the duration or intensity of active monitoring.",2018 Jan 18,"['Reich, Nicholas G.', 'Lessler, Justin', 'Varma, Jay K.', 'Vora, Neil M.']",Sci Rep,,,True
87c3200763e5eb133e57001643a002ae67fc99bd,PMC,GenomeLandscaper: Landscape analysis of genome-fingerprints maps assessing chromosome architecture,http://dx.doi.org/10.1038/s41598-018-19366-2,PMC5773709,29348569,CC BY,"Assessing correctness of an assembled chromosome architecture is a central challenge. We create a geometric analysis method (called GenomeLandscaper) to conduct landscape analysis of genome-fingerprints maps (GFM), trace large-scale repetitive regions, and assess their impacts on the global architectures of assembled chromosomes. We develop an alignment-free method for phylogenetics analysis. The human Y chromosomes (GRCh.chrY, HuRef.chrY and YH.chrY) are analysed as a proof-of-concept study. We construct a galaxy of genome-fingerprints maps (GGFM) for them, and a landscape compatibility among relatives is observed. But a long sharp straight line on the GGFM breaks such a landscape compatibility, distinguishing GRCh38p1.chrY (and throughout GRCh38p7.chrY) from GRCh37p13.chrY, HuRef.chrY and YH.chrY. We delete a 1.30-Mbp target segment to rescue the landscape compatibility, matching the antecedent GRCh37p13.chrY. We re-locate it into the modelled centromeric and pericentromeric region of GRCh38p10.chrY, matching a gap placeholder of GRCh37p13.chrY. We decompose it into sub-constituents (such as BACs, interspersed repeats, and tandem repeats) and trace their homologues by phylogenetics analysis. We elucidate that most examined tandem repeats are of reasonable quality, but the BAC-sized repeats, 173U1020C (176.46 Kbp) and 5U41068C (205.34 Kbp), are likely over-repeated. These results offer unique insights into the centromeric and pericentromeric regions of the human Y chromosomes.",2018 Jan 18,"['Ai, Hannan', 'Ai, Yuncan', 'Meng, Fanmei']",Sci Rep,,,False
b72e220b6500d2251e103f23d64b2f96f6e082f2,PMC,GenomeLandscaper: Landscape analysis of genome-fingerprints maps assessing chromosome architecture,http://dx.doi.org/10.1038/s41598-018-19366-2,PMC5773709,29348569,CC BY,"Assessing correctness of an assembled chromosome architecture is a central challenge. We create a geometric analysis method (called GenomeLandscaper) to conduct landscape analysis of genome-fingerprints maps (GFM), trace large-scale repetitive regions, and assess their impacts on the global architectures of assembled chromosomes. We develop an alignment-free method for phylogenetics analysis. The human Y chromosomes (GRCh.chrY, HuRef.chrY and YH.chrY) are analysed as a proof-of-concept study. We construct a galaxy of genome-fingerprints maps (GGFM) for them, and a landscape compatibility among relatives is observed. But a long sharp straight line on the GGFM breaks such a landscape compatibility, distinguishing GRCh38p1.chrY (and throughout GRCh38p7.chrY) from GRCh37p13.chrY, HuRef.chrY and YH.chrY. We delete a 1.30-Mbp target segment to rescue the landscape compatibility, matching the antecedent GRCh37p13.chrY. We re-locate it into the modelled centromeric and pericentromeric region of GRCh38p10.chrY, matching a gap placeholder of GRCh37p13.chrY. We decompose it into sub-constituents (such as BACs, interspersed repeats, and tandem repeats) and trace their homologues by phylogenetics analysis. We elucidate that most examined tandem repeats are of reasonable quality, but the BAC-sized repeats, 173U1020C (176.46 Kbp) and 5U41068C (205.34 Kbp), are likely over-repeated. These results offer unique insights into the centromeric and pericentromeric regions of the human Y chromosomes.",2018 Jan 18,"['Ai, Hannan', 'Ai, Yuncan', 'Meng, Fanmei']",Sci Rep,,,True
33f48f3ce2b476338c67cddb65732d26806377bd,PMC,Incidence and risk factors of postoperative pneumonia following cancer surgery in adult patients with selected solid cancer: results of “Cancer POP” study,http://dx.doi.org/10.1002/cam4.1259,PMC5773948,29271081,CC BY,"The aim of this study was to investigate the incidence and risk factors of postoperative pneumonia (POP) within 1 year after cancer surgery in patients with the five most common cancers (gastric, colorectal, lung, breast cancer, and hepatocellular carcinoma [HCC]) in South Korea. This was a multicenter and retrospective cohort study performed at five nationwide cancer centers. The number of cancer patients in each center was allocated by the proportion of cancer surgery. Adult patients were randomly selected according to the allocated number, among those who underwent cancer surgery from January to December 2014 within 6 months after diagnosis of cancer. One‐year cumulative incidence of POP was estimated using Kaplan–Meier analysis. An univariable Cox's proportional hazard regression analysis was performed to identify risk factors for POP development. As a multivariable analysis, confounders were adjusted using multiple Cox's PH regression model. Among the total 2000 patients, the numbers of patients with gastric cancer, colorectal cancer, lung cancer, breast cancer, and HCC were 497 (25%), 525 (26%), 277 (14%), 552 (28%), and 149 (7%), respectively. Overall, the 1‐year cumulative incidence of POP was 2.0% (95% CI, 1.4–2.6). The 1‐year cumulative incidences in each cancer were as follows: lung 8.0%, gastric 1.8%, colorectal 1.0%, HCC 0.7%, and breast 0.4%. In multivariable analysis, older age, higher Charlson comorbidity index (CCI) score, ulcer disease, history of pneumonia, and smoking were related with POP development. In conclusions, the 1‐year cumulative incidence of POP in the five most common cancers was 2%. Older age, higher CCI scores, smoker, ulcer disease, and previous pneumonia history increased the risk of POP development in cancer patients.",2017 Dec 22,"['Jung, Jiwon', 'Moon, Song Mi', 'Jang, Hee‐Chang', 'Kang, Cheol‐In', 'Jun, Jae‐Bum', 'Cho, Yong Kyun', 'Kang, Seung‐Ji', 'Seo, Bo‐Jeong', 'Kim, Young‐Joo', 'Park, Seong‐Beom', 'Lee, Juneyoung', 'Yu, Chang Sik', 'Kim, Sung‐Han']",Cancer Med,,,True
6cd8cfb4dd10db30a8bbd630da2e8c15ee4e4956,PMC,MicroRNA transcriptome analysis of porcine vital organ responses to immunosuppressive porcine cytomegalovirus infection,http://dx.doi.org/10.1186/s12985-018-0922-x,PMC5774105,29347945,CC BY,"BACKGROUND: Porcine cytomegalovirus (PCMV) is an immunosuppressive virus that mainly inhibits T-lymphocyte and macrophage immune functions; it has significantly damaged the farming industry. Although recent studies have shown that miRNAs play important roles in immune responses, the regulatory mechanisms of miRNAs during immunosuppressive virus infection remain unclear. METHODS: In this study, porcine small-RNA transcriptomes of PCMV-infected and uninfected vital organs were first characterised by high-throughput sequencing. miRDeep2 software was used to predict novel pig-encoded miRNAs. To verify the accuracy of the high-throughput sequencing results, stem-loop qRT-PCR was performed on 12 significantly DE miRNAs. The physical and functional interactions between the immune-related target genes of the DE miRNAs in PCMV-infected organs were analysed using the STRING database. RESULTS: In total, 306 annotated and 295 novel miRNAs were identified from PCMV-infected and uninfected porcine organs, respectively, through alignment with known Sus scrofa pre-miRNAs. Overall, 92, 107, 95, 77 and 111 miRNAs were significantly differentially expressed in lung, liver, spleen, kidney and thymus after PCMV infection, respectively. According to Gene Ontology enrichment analysis, target genes of the differentially expressed miRNAs associated with immune system processes, regulation of biological processes and metabolic processes were enriched in every sample. Integrated expression analysis of the differentially expressed miRNAs and their target mRNAs in PCMV-infected thymus showed that the significant differential expression of specific miRNAs under the pressure of PCMV infection in central immune organs interfered with the expression of genes involved in important immune-related signalling pathways, thus promoting the viral infection. CONCLUSIONS: This is the first comprehensive analysis of the responses of host small-RNA transcriptomes to PCMV infection in vital porcine organs. It provides new insights into the regulatory mechanisms of miRNAs during infection by immunosuppressive viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-0922-x) contains supplementary material, which is available to authorized users.",2018 Jan 18,"['Liu, Xiao', 'Wei, Haoche', 'Liao, Shan', 'Ye, Jianheng', 'Zhu, Ling', 'Xu, Zhiwen']",Virol J,,,True
47cf6a3f1e96d00834269394edef8c83f61ef1c9,PMC,"Use of influenza antivirals in patients hospitalized in Hong Kong, 2000-2015",http://dx.doi.org/10.1371/journal.pone.0190306,PMC5774686,29351330,CC BY,"OBJECTIVES: We aimed to describe patterns in the usage of antivirals to treat influenza virus infection in hospitals in Hong Kong from 2000 through 2015. METHODS: We analyzed centralized electronic health records that included dispensation information and diagnosis codes. Information collected on admissions included patient age, sex, admission year and month, and medications dispensed, and were matched with the first 15 discharge diagnosis codes. We divided monthly admission episodes by relevant population denominators to obtain admission rates, and stratified analyses by drug type, age group, and diagnosis codes. RESULTS: Amantadine was used for influenza treatment in the early 2000s but changed with recommendations to avoid its use in 2006, and is now mainly used to treat Parkinson’s disease. Oseltamivir usage increased substantially in 2009 and is now commonly used, with almost 40,000 hospitalizations treated with oseltamivir in the years 2012 through 2015, 66% of which was in persons ≥65 years of age. During the entire study period, of the 98,253 admission episodes in which oseltamivir was dispensed, 40,698 (41%) included a diagnosis code for influenza, and 80,283 (82%) included any diagnosis code for respiratory illness. CONCLUSIONS: The amount of oseltamivir used from 2012–15 was comparable to a separate ecological estimate of around 13,000 influenza-associated hospitalizations per year on average. We did not have access to individual patient laboratory testing data.",2018 Jan 19,"['Cowling, Benjamin J.', 'Chui, Celine S. L.', 'Lim, Wey Wen', 'Wu, Peng', 'Hui, Christopher K. M.', 'Peiris, J. S. Malik', 'Chan, Esther W.']",PLoS One,,,True
51dd0bdd5680a978bf834d5b4cbfaa8dd84dea90,PMC,Clinical and microbiologic efficacy of the piperazine-based drug lead MMV665917 in the dairy calf cryptosporidiosis model,http://dx.doi.org/10.1371/journal.pntd.0006183,PMC5774826,29309415,CC BY,"Cryptosporidiosis causes life-threatening diarrhea in infants, but the best available treatment is only modestly efficacious. Rodents infected with relevant Cryptosporidium species do not develop diarrhea, which complicates drug development. Cryptosporidium parvum infection of dairy calves, however, causes an illness like that seen in infants. Here, the clinical and microbiologic anti-Cryptosporidium efficacy of the piperazine-based compound MMV665917 was demonstrated in neonatal calves. Oral administration of MMV665917 (22 mg/kg once daily) was begun two days after the onset of severe diarrhea and continued for seven days. Treatment resulted in prompt resolution of diarrhea, and reduced total fecal oocyst shedding by ~94%. MMV665917 was useful for treatment, rather than just prophylaxis, since it was safe and effective when administered well after the onset of diarrhea. Furthermore, even though all animals received intensive supportive care, there was a strong trend towards improved secondary health outcomes, including general health, appetite, and dehydration measures amongst treated animals. These data establish MMV665917 as an outstanding lead compound for Cryptosporidium drug development.",2018 Jan 8,"['Stebbins, Erin', 'Jumani, Rajiv S.', 'Klopfer, Connor', 'Barlow, John', 'Miller, Peter', 'Campbell, Mary A.', 'Meyers, Marvin J.', 'Griggs, David W.', 'Huston, Christopher D.']",PLoS Negl Trop Dis,,,True
15d37cf2a310ff8cce48b1c1f3eaea846b17bbd2,PMC,Global trends in research related to social media in psychology: mapping and bibliometric analysis,http://dx.doi.org/10.1186/s13033-018-0182-6,PMC5775539,29387147,CC BY,"BACKGROUND: Social media, defined as interactive Web applications, have been on the rise globally, particularly among adults. The objective of this study was to investigate the trend of the literature related to the most used social network worldwide (i.e. Facebook, Twitter, LinkedIn, Snapchat, and Instagram) in the field of psychology. Specifically, this study will assess the growth in publications, citation analysis, international collaboration, author productivity, emerging topics and the mapping of frequent terms in publications pertaining to social media in the field of psychology. METHODS: Publications related to social media in the field of psychology published between 2004 and 2014 were obtained from the Web of Science. The records extracted were analysed for bibliometric characteristics such as the growth in publications, citation analysis, international collaboration, emerging topics and the mapping of frequent terms in publications pertaining to social media in the field of psychology. VOSviewer v.1.6.5 was used to construct scientific maps. RESULTS: Overall, 959 publications were retrieved during the period between 2004 and 2015. The number of research publications in social media in the field of psychology showed a steady upward growth. Publications from the USA accounted for 57.14% of the total publications and the highest h-index (48).The most common document type was research articles (873; 91.03%). Over 99.06% of the publications were published in English. Computers in Human Behavior was the most prolific journal. The University of Wisconsin–Madison ranked first in terms of the total publications (n = 39). A visualisation analysis showed that personality psychology, experimental psychology, psychological risk factors, and developmental psychology were continual concerns of the research. CONCLUSIONS: This is the first study reporting the global trends in the research related to social media in the psychology field. Based on the raw data from the Web of Science, publication characteristics such as quality and quantity were assessed using bibliometric techniques over 12 years. The USA and its institutions play a dominant role in this topic. The most preferred topics related to social media in psychology are personality psychology, experimental psychology, psychological risk factors, and developmental psychology.",2018 Jan 19,"['Zyoud, Sa’ed H.', 'Sweileh, Waleed M.', 'Awang, Rahmat', 'Al-Jabi, Samah W.']",Int J Ment Health Syst,,,True
b1be7d31c3101fa5b0c803ee2d354eb7d3943526,PMC,"Gemcitabine, a broad-spectrum antiviral drug, suppresses enterovirus infections through innate immunity induced by the inhibition of pyrimidine biosynthesis and nucleotide depletion",http://dx.doi.org/10.18632/oncotarget.23258,PMC5777774,29383162,CC BY,"Gemcitabine, an anti-cancer chemotherapy drug, has additionally shown the antiviral activity against a broad range of viruses and we also have previously reported its synergistic antiviral activity with ribavirin against enteroviruses. As a cytidine analog, gemcitabine has been reported to have an inhibitory activity on the pyrimidine biosynthesis. In addition, a few inhibitors of the pyrimidine biosynthesis have shown to induce the innate immunity in a yet-to-be-determined manner and inhibit the virus infection. Thus, we also investigated whether the anti-enteroviral activity of gemcitabine is mediated by innate immunity, induction of which is related with the inhibition of the pyrimidine synthesis. In this study, we found that the addition of exogenous cytidine, uridine and uridine mono-phosphate (UMP) effectively reversed the antiviral activity of gemcitabine in enterovirus-infected as well as enteroviral replicon-harboring cells, demonstrating gemcitabine’s targeting of the salvage pathway. Moreover, the expression of several interferon (IFN)-stimulated genes (ISGs) was significantly induced by the treatment of gemcitabine, which was also suppressed by the co-treatment with cytidine. These results suggest that the antiviral activity of gemcitabine involves ISGs induced by the inhibition of the pyrimidine biosynthesis.",2017 Dec 15,"['Lee, Kyungjin', 'Kim, Dong-Eun', 'Jang, Kyoung-Soon', 'Kim, Seong-Jun', 'Cho, Sungchan', 'Kim, Chonsaeng']",Oncotarget,,,True
0c7868e5dd3759240c125cfa1d28c4fbe0ffb91b,PMC,"Gemcitabine, a broad-spectrum antiviral drug, suppresses enterovirus infections through innate immunity induced by the inhibition of pyrimidine biosynthesis and nucleotide depletion",http://dx.doi.org/10.18632/oncotarget.23258,PMC5777774,29383162,CC BY,"Gemcitabine, an anti-cancer chemotherapy drug, has additionally shown the antiviral activity against a broad range of viruses and we also have previously reported its synergistic antiviral activity with ribavirin against enteroviruses. As a cytidine analog, gemcitabine has been reported to have an inhibitory activity on the pyrimidine biosynthesis. In addition, a few inhibitors of the pyrimidine biosynthesis have shown to induce the innate immunity in a yet-to-be-determined manner and inhibit the virus infection. Thus, we also investigated whether the anti-enteroviral activity of gemcitabine is mediated by innate immunity, induction of which is related with the inhibition of the pyrimidine synthesis. In this study, we found that the addition of exogenous cytidine, uridine and uridine mono-phosphate (UMP) effectively reversed the antiviral activity of gemcitabine in enterovirus-infected as well as enteroviral replicon-harboring cells, demonstrating gemcitabine’s targeting of the salvage pathway. Moreover, the expression of several interferon (IFN)-stimulated genes (ISGs) was significantly induced by the treatment of gemcitabine, which was also suppressed by the co-treatment with cytidine. These results suggest that the antiviral activity of gemcitabine involves ISGs induced by the inhibition of the pyrimidine biosynthesis.",2017 Dec 15,"['Lee, Kyungjin', 'Kim, Dong-Eun', 'Jang, Kyoung-Soon', 'Kim, Seong-Jun', 'Cho, Sungchan', 'Kim, Chonsaeng']",Oncotarget,,,False
0e8f07d17aaa0e83209868716d79a4527952c0ba,PMC,MERS-CoV spillover at the camel-human interface,http://dx.doi.org/10.7554/eLife.31257,PMC5777824,29336306,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus from camels causing significant mortality and morbidity in humans in the Arabian Peninsula. The epidemiology of the virus remains poorly understood, and while case-based and seroepidemiological studies have been employed extensively throughout the epidemic, viral sequence data have not been utilised to their full potential. Here, we use existing MERS-CoV sequence data to explore its phylodynamics in two of its known major hosts, humans and camels. We employ structured coalescent models to show that long-term MERS-CoV evolution occurs exclusively in camels, whereas humans act as a transient, and ultimately terminal host. By analysing the distribution of human outbreak cluster sizes and zoonotic introduction times, we show that human outbreaks in the Arabian peninsula are driven by seasonally varying zoonotic transfer of viruses from camels. Without heretofore unseen evolution of host tropism, MERS-CoV is unlikely to become endemic in humans.",,"['Dudas, Gytis', 'Carvalho, Luiz Max', 'Rambaut, Andrew', 'Bedford, Trevor']",eLife.; 7:e31257,,,True
4343b8a2d6913f659a94a8c4b08747ae9bbe7890,PMC,MERS-CoV spillover at the camel-human interface,http://dx.doi.org/10.7554/eLife.31257,PMC5777824,29336306,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus from camels causing significant mortality and morbidity in humans in the Arabian Peninsula. The epidemiology of the virus remains poorly understood, and while case-based and seroepidemiological studies have been employed extensively throughout the epidemic, viral sequence data have not been utilised to their full potential. Here, we use existing MERS-CoV sequence data to explore its phylodynamics in two of its known major hosts, humans and camels. We employ structured coalescent models to show that long-term MERS-CoV evolution occurs exclusively in camels, whereas humans act as a transient, and ultimately terminal host. By analysing the distribution of human outbreak cluster sizes and zoonotic introduction times, we show that human outbreaks in the Arabian peninsula are driven by seasonally varying zoonotic transfer of viruses from camels. Without heretofore unseen evolution of host tropism, MERS-CoV is unlikely to become endemic in humans.",,"['Dudas, Gytis', 'Carvalho, Luiz Max', 'Rambaut, Andrew', 'Bedford, Trevor']",eLife.; 7:e31257,,,False
219db23666b8e31245a5a93f4c8bda3606449296,PMC,Current progress in innovative engineered antibodies,http://dx.doi.org/10.1007/s13238-017-0457-8,PMC5777977,28822103,CC BY,"As of May 1, 2017, 74 antibody-based molecules have been approved by a regulatory authority in a major market. Additionally, there are 70 and 575 antibody-based molecules in phase III and phase I/II clinical trials, respectively. These total 719 antibody-based clinical stage molecules include 493 naked IgGs, 87 antibody-drug conjugates, 61 bispecific antibodies, 37 total Fc fusion proteins, 17 radioimmunoglobulins, 13 antibody fragments, and 11 immunocytokines. New uses for these antibodies are being discovered each year. For oncology, many of the exciting new approaches involve antibody modulation of T-cells. There are over 80 antibodies in clinical trials targeting T cell checkpoints, 26 T-cell-redirected bispecific antibodies, and 145 chimeric antigen receptor (CAR) cell-based candidates (all currently in phase I or II clinical trials), totaling more than 250 T cell interacting clinical stage antibody-based candidates. Finally, significant progress has been made recently on routes of delivery, including delivery of proteins across the blood-brain barrier, oral delivery to the gut, delivery to the cellular cytosol, and gene- and viral-based delivery of antibodies. Thus, there are currently at least 864 antibody-based clinical stage molecules or cells, with incredible diversity in how they are constructed and what activities they impart. These are followed by a next wave of novel molecules, approaches, and new methods and routes of delivery, demonstrating that the field of antibody-based biologics is very innovative and diverse in its approaches to fulfill their promise to treat unmet medical needs.",2018 Jan 18,"Strohl, William R.",Protein Cell,,,True
f3598c3dfc758286cc4af164c6cfb66f5bd4826d,PMC,Ribosome profiling of the retrovirus murine leukemia virus,http://dx.doi.org/10.1186/s12977-018-0394-5,PMC5778647,29357872,CC BY,"BACKGROUND: The retrovirus murine leukemia virus (MuLV) has an 8.3 kb RNA genome with a simple 5′-gag-pol-env-3′ architecture. Translation of the pol gene is dependent upon readthrough of the gag UAG stop codon; whereas the env gene is translated from spliced mRNA transcripts. Here, we report the first high resolution analysis of retrovirus gene expression through tandem ribosome profiling (RiboSeq) and RNA sequencing (RNASeq) of MuLV-infected cells. RESULTS: Ribosome profiling of MuLV-infected cells was performed, using the translational inhibitors harringtonine and cycloheximide to distinguish initiating and elongating ribosomes, respectively. Meta-analyses of host cell gene expression demonstrated that the RiboSeq datasets specifically captured the footprints of translating ribosomes at high resolution. Direct measurement of ribosomal occupancy of the MuLV genomic RNA indicated that ~ 7% of ribosomes undergo gag stop codon readthrough to access the pol gene. Initiation of translation was found to occur at several additional sites within the 5′ leaders of the gag and env transcripts, upstream of their respective annotated start codons. CONCLUSIONS: These experiments reveal the existence of a number of previously uncharacterised, ribosomally occupied open reading frames within the MuLV genome, with possible regulatory consequences. In addition, we provide the first direct measurements of stop codon readthrough efficiency during cellular infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12977-018-0394-5) contains supplementary material, which is available to authorized users.",2018 Jan 22,"['Irigoyen, Nerea', 'Dinan, Adam M.', 'Brierley, Ian', 'Firth, Andrew E.']",Retrovirology,,,False
7dffa969edbe8096420d429681024410840d4d20,PMC,Ribosome profiling of the retrovirus murine leukemia virus,http://dx.doi.org/10.1186/s12977-018-0394-5,PMC5778647,29357872,CC BY,"BACKGROUND: The retrovirus murine leukemia virus (MuLV) has an 8.3 kb RNA genome with a simple 5′-gag-pol-env-3′ architecture. Translation of the pol gene is dependent upon readthrough of the gag UAG stop codon; whereas the env gene is translated from spliced mRNA transcripts. Here, we report the first high resolution analysis of retrovirus gene expression through tandem ribosome profiling (RiboSeq) and RNA sequencing (RNASeq) of MuLV-infected cells. RESULTS: Ribosome profiling of MuLV-infected cells was performed, using the translational inhibitors harringtonine and cycloheximide to distinguish initiating and elongating ribosomes, respectively. Meta-analyses of host cell gene expression demonstrated that the RiboSeq datasets specifically captured the footprints of translating ribosomes at high resolution. Direct measurement of ribosomal occupancy of the MuLV genomic RNA indicated that ~ 7% of ribosomes undergo gag stop codon readthrough to access the pol gene. Initiation of translation was found to occur at several additional sites within the 5′ leaders of the gag and env transcripts, upstream of their respective annotated start codons. CONCLUSIONS: These experiments reveal the existence of a number of previously uncharacterised, ribosomally occupied open reading frames within the MuLV genome, with possible regulatory consequences. In addition, we provide the first direct measurements of stop codon readthrough efficiency during cellular infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12977-018-0394-5) contains supplementary material, which is available to authorized users.",2018 Jan 22,"['Irigoyen, Nerea', 'Dinan, Adam M.', 'Brierley, Ian', 'Firth, Andrew E.']",Retrovirology,,,True
2baa5a272429873854470fa3f3cec0c91264f5d5,PMC,Temporary carriage of bovine coronavirus and bovine respiratory syncytial virus by fomites and human nasal mucosa after exposure to infected calves,http://dx.doi.org/10.1186/s12917-018-1335-1,PMC5778652,29357935,CC BY,"BACKGROUND: In order to prevent spread of the endemic pathogens bovine coronavirus (BCoV) and bovine respiratory syncytial virus (BRSV) between herds, knowledge of indirect transmission by personnel and fomites is fundamental. The aims of the study were to determine the duration of viral RNA carriage and the infectivity of viral particles on fomites and human nasal mucosa after exposure to BCoV and BRSV. During two animal infection experiments, swabs were collected from personnel (nasal mucosa) and their clothes, boots and equipment after contact with calves shedding either virus. Viral RNA was quantified by RT-qPCR or droplet digital RT-PCR (RT-ddPCR), and selected samples with high levels of viral RNA were tested by cell culture for infectivity. RESULTS: For BCoV, 46% (n = 80) of the swabs from human nasal mucosa collected 30 min after exposure were positive by RT-qPCR. After two, four and six hours, 15%, 5% and 0% of the swabs were positive, respectively. Infective virions were not detected in mucosal swabs (n = 2). A high viral RNA load was detected on 97% (n = 44) of the fomites 24 h after exposure, and infective virions were detected in two of three swabs. For BRSV, 35% (n = 26) of the human nasal mucosa swabs collected 30 min after exposure, were positive by RT-ddPCR, but none were positive for infective virions. Of the fomites, 89% (n = 38) were positive for BRSV RNA 24 h after exposure, but all were negative for infective viruses. CONCLUSIONS: The results indicate that human nasal mucosa can carry both BCoV and BRSV RNA after exposure to virus shedding calves, but the carriage seems short-lived and the transmission potential is likely limited. High viral loads on contaminates fomites 24 h after exposure to infected animals, and detection of infective BCoV, indicate that contaminated fomites represent a significant risk for indirect transmission between herds.",2018 Jan 22,"['Oma, Veslemøy Sunniva', 'Klem, Thea', 'Tråvén, Madeleine', 'Alenius, Stefan', 'Gjerset, Britt', 'Myrmel, Mette', 'Stokstad, Maria']",BMC Vet Res,,,True
85d7376aca04b7df9b23618734948c2814ccfe19,PMC,Immunostimulatory activity of water-extractable polysaccharides from Cistanche deserticola as a plant adjuvant in vitro and in vivo,http://dx.doi.org/10.1371/journal.pone.0191356,PMC5779666,29360858,CC BY,"A safe and effective vaccine adjuvant is important in modern vaccines. Various Chinese herbal polysaccharides can activate the immune system. Cistanche deserticola (CD) is a traditional Chinese herb and an adjuvant candidate. Here, we confirmed that water-extractable polysaccharides of CD (WPCD) could modulate immune responses in vitro and in vivo. In a dose-dependent manner, WPCD significantly promoted the maturation and function of murine marrow-derived dendritic cells (BM-DCs) through up-regulating the expression levels of MHC-II, CD86, CD80, and CD40, allogenic T cell proliferation, and the yields of IL-12 and TNF-α via toll-like receptor4 (TLR4), as indicated by in vitro experiments. In addition, its immunomodulatory activity was also observed in mice. WPCD effectively improved the titers of IgG, IgG(1) and IgG(2a) and markedly enhanced the proliferation of T and B cells, the production of IFN-γ and IL-4 in CD4(+) T cells and the expression level of IFN-γ in CD8(+) T cells better than Alum. Furthermore, WPCD could markedly up-regulate the expression levels of CD40 and CD80 on DCs in spleen and down-regulate the Treg frequency. The study suggests that polysaccharides of Cistanche deserticola are a safe and effective vaccine adjuvant for eliciting both humoral immunity and cellular immunity by activating DCs via TLR4 signaling pathway.",2018 Jan 23,"['Zhang, Ailian', 'Yang, Xiumei', 'Li, Quanxiao', 'Yang, Yu', 'Zhao, Gan', 'Wang, Bin', 'Wu, Daocheng']",PLoS One,,,True
46833c3f5dcabbe5e696a5d76d61dec64422a433,PMC,Protein Palmitoylation and Its Role in Bacterial and Viral Infections,http://dx.doi.org/10.3389/fimmu.2017.02003,PMC5780409,29403483,CC BY,"S-palmitoylation is a reversible, enzymatic posttranslational modification of proteins in which palmitoyl chain is attached to a cysteine residue via a thioester linkage. S-palmitoylation determines the functioning of proteins by affecting their association with membranes, compartmentalization in membrane domains, trafficking, and stability. In this review, we focus on S-palmitoylation of proteins, which are crucial for the interactions of pathogenic bacteria and viruses with the host. We discuss the role of palmitoylated proteins in the invasion of host cells by bacteria and viruses, and those involved in the host responses to the infection. We highlight recent data on protein S-palmitoylation in pathogens and their hosts obtained owing to the development of methods based on click chemistry and acyl-biotin exchange allowing proteomic analysis of protein lipidation. The role of the palmitoyl moiety present in bacterial lipopolysaccharide and lipoproteins, contributing to infectivity and affecting recognition of bacteria by innate immune receptors, is also discussed.",2018 Jan 19,"['Sobocińska, Justyna', 'Roszczenko-Jasińska, Paula', 'Ciesielska, Anna', 'Kwiatkowska, Katarzyna']",Front Immunol,,,True
82c17f8de937704b2522db77b863f8f01ab19414,PMC,"Epidemiology and clinical characteristics of human coronaviruses OC43, 229E, NL63, and HKU1: a study of hospitalized children with acute respiratory tract infection in Guangzhou, China",http://dx.doi.org/10.1007/s10096-017-3144-z,PMC5780525,29214503,CC BY,"Human coronaviruses (HCoV) OC43, 229E, NL63, and HKU1 are common respiratory viruses which cause various respiratory diseases, including pneumonia. There is a paucity of evidence on the epidemiology and clinical manifestations of these four HCoV strains worldwide. We collected 11,399 throat swabs from hospitalized children with acute respiratory tract infection from July 2009 to June 2016 in Guangzhou, China. These were tested for four strains of HCoV infection using real-time polymerase chain reaction (PCR). HCoV-positive patients were then tested for 11 other respiratory pathogens. 4.3% (489/11399) of patients were positive for HCoV, of which 3.0% were positive for OC43 (346/11399), 0.6% for 229E (65/11399), 0.5% for NL63 (60/11399), and 0.3% for HKU1 (38/11399). Patients aged 7–12 months had the highest prevalence of HCoV and OC43 when compared with other age groups (p < 0.001). The peak seasons of infection varied depending on the HCoV strain. Patients infected with a single strain of HCoV infection were less likely to present fever (≥ 38 °C) (p = 0.014) and more likely to present pulmonary rales (p = 0.043) than those co-infected with more than one HCoV strain or other respiratory pathogens. There were also significant differences in the prevalence of certain symptoms, including coughing (p = 0.032), pneumonia (p = 0.026), and abnormal pulmonary rales (p = 0.002) according to the strain of HCoV detected. This retrospective study of the prevalence of four HCoV strains and clinical signs among a large population of pediatric patients in a subtropical region of China provides further insight into the epidemiology and clinical features of HCoV.",2018 Dec 6,"['Zeng, Zhi-Qi', 'Chen, De-Hui', 'Tan, Wei-Ping', 'Qiu, Shu-Yan', 'Xu, Duo', 'Liang, Huan-Xi', 'Chen, Mei-Xin', 'Li, Xiao', 'Lin, Zheng-Shi', 'Liu, Wen-Kuan', 'Zhou, Rong']",Eur J Clin Microbiol Infect Dis,,,True
e50c8a016885a30fcf67cee1b1e70c56b5c27e2a,PMC,"Retrospective analysis assessing the spatial and temporal distribution of paediatric acute respiratory tract infections in Ho Chi Minh City, Vietnam",http://dx.doi.org/10.1136/bmjopen-2017-016349,PMC5780701,29358416,CC BY,"BACKGROUND: Acute respiratory tract infections (ARIs) are the leading cause of morbidity and mortality in young children in low/middle-income countries. Using routine hospital data, we aimed to examine the spatial distribution, temporal trends and climatic risk factors of paediatric ARIs in Vietnam. METHODS: Data from hospitalised paediatric (<16 years) patients with ARIs residing in Ho Chi Minh City (HCMC) between 2005 and 2010 were retrieved from the two main Children’s Hospitals and the Hospital for Tropical Diseases in HCMC. Spatial mapping and time series analysis were performed after disaggregating data into upper respiratory tract infections (URIs) and lower respiratory tract infections (LRIs). RESULTS: Over the study period, there were 155 999 paediatric patients admitted with ARIs (33% of all hospital admissions). There were 68 120 URIs (14%) and 87 879 LRIs (19%). The most common diagnoses were acute pharyngitis (28% of all ARI), pneumonia (21%), bronchitis (18%) and bronchiolitis (16%). A significant increasing trend over time was found for both URIs (mean weekly incidence per 1000 population, I=3.12), incidence rate ratio for 1-week increase in time (RR 1.0, 95% CI 1.02 to 1.17) for URI and (I=4.02, RR 1.08 (95% CI 1.006 to 1.16)) for LRI. The weekly URI incidence peaked in May–June and was significantly associated with lags in weekly URI incidence and the average humidity, rainfall and water level. The weekly LRI incidence exhibited significant seasonality (P<0.0001), with an annual peak in September–October and was significantly associated with lags in weekly LRI incidence and lags in weekly average temperature, rainfall and water level. CONCLUSIONS: ARIs are a leading cause of childhood hospitalisation in HCMC, Vietnam. The incidence of ARIs was higher in the wet season and in specific HCMC districts. These results may guide health authorities in where and when to effectively allocate resources for the prevention and control of ARIs.",2018 Jan 21,"['Ho, Nhan Thi', 'Thompson, Corinne', 'Nhan, Le Nguyen Thanh', 'Van, Hoang Minh Tu', 'Dung, Nguyen Thanh', 'Tran My, Phuc', 'Quang, Vo Minh', 'Minh, Ngo Ngoc Quang', 'Tuan, Tran Anh', 'Hung, Nguyen Thanh', 'Tuan, Ha Manh', 'Vinh Chau, Nguyen Van', 'Wolbers, Marcel', 'Thwaites, Guy E', 'Choisy, Marc', 'Baker, Stephen']",BMJ Open,,,True
2975cca0a160177ac01195442ee8f6a55c59bd24,PMC,"Retrospective analysis assessing the spatial and temporal distribution of paediatric acute respiratory tract infections in Ho Chi Minh City, Vietnam",http://dx.doi.org/10.1136/bmjopen-2017-016349,PMC5780701,29358416,CC BY,"BACKGROUND: Acute respiratory tract infections (ARIs) are the leading cause of morbidity and mortality in young children in low/middle-income countries. Using routine hospital data, we aimed to examine the spatial distribution, temporal trends and climatic risk factors of paediatric ARIs in Vietnam. METHODS: Data from hospitalised paediatric (<16 years) patients with ARIs residing in Ho Chi Minh City (HCMC) between 2005 and 2010 were retrieved from the two main Children’s Hospitals and the Hospital for Tropical Diseases in HCMC. Spatial mapping and time series analysis were performed after disaggregating data into upper respiratory tract infections (URIs) and lower respiratory tract infections (LRIs). RESULTS: Over the study period, there were 155 999 paediatric patients admitted with ARIs (33% of all hospital admissions). There were 68 120 URIs (14%) and 87 879 LRIs (19%). The most common diagnoses were acute pharyngitis (28% of all ARI), pneumonia (21%), bronchitis (18%) and bronchiolitis (16%). A significant increasing trend over time was found for both URIs (mean weekly incidence per 1000 population, I=3.12), incidence rate ratio for 1-week increase in time (RR 1.0, 95% CI 1.02 to 1.17) for URI and (I=4.02, RR 1.08 (95% CI 1.006 to 1.16)) for LRI. The weekly URI incidence peaked in May–June and was significantly associated with lags in weekly URI incidence and the average humidity, rainfall and water level. The weekly LRI incidence exhibited significant seasonality (P<0.0001), with an annual peak in September–October and was significantly associated with lags in weekly LRI incidence and lags in weekly average temperature, rainfall and water level. CONCLUSIONS: ARIs are a leading cause of childhood hospitalisation in HCMC, Vietnam. The incidence of ARIs was higher in the wet season and in specific HCMC districts. These results may guide health authorities in where and when to effectively allocate resources for the prevention and control of ARIs.",2018 Jan 21,"['Ho, Nhan Thi', 'Thompson, Corinne', 'Nhan, Le Nguyen Thanh', 'Van, Hoang Minh Tu', 'Dung, Nguyen Thanh', 'Tran My, Phuc', 'Quang, Vo Minh', 'Minh, Ngo Ngoc Quang', 'Tuan, Tran Anh', 'Hung, Nguyen Thanh', 'Tuan, Ha Manh', 'Vinh Chau, Nguyen Van', 'Wolbers, Marcel', 'Thwaites, Guy E', 'Choisy, Marc', 'Baker, Stephen']",BMJ Open,,,True
5fa442d7a4a81f82d7c5f0ecc72ab708ac2a7266,PMC,"Retrospective analysis assessing the spatial and temporal distribution of paediatric acute respiratory tract infections in Ho Chi Minh City, Vietnam",http://dx.doi.org/10.1136/bmjopen-2017-016349,PMC5780701,29358416,CC BY,"BACKGROUND: Acute respiratory tract infections (ARIs) are the leading cause of morbidity and mortality in young children in low/middle-income countries. Using routine hospital data, we aimed to examine the spatial distribution, temporal trends and climatic risk factors of paediatric ARIs in Vietnam. METHODS: Data from hospitalised paediatric (<16 years) patients with ARIs residing in Ho Chi Minh City (HCMC) between 2005 and 2010 were retrieved from the two main Children’s Hospitals and the Hospital for Tropical Diseases in HCMC. Spatial mapping and time series analysis were performed after disaggregating data into upper respiratory tract infections (URIs) and lower respiratory tract infections (LRIs). RESULTS: Over the study period, there were 155 999 paediatric patients admitted with ARIs (33% of all hospital admissions). There were 68 120 URIs (14%) and 87 879 LRIs (19%). The most common diagnoses were acute pharyngitis (28% of all ARI), pneumonia (21%), bronchitis (18%) and bronchiolitis (16%). A significant increasing trend over time was found for both URIs (mean weekly incidence per 1000 population, I=3.12), incidence rate ratio for 1-week increase in time (RR 1.0, 95% CI 1.02 to 1.17) for URI and (I=4.02, RR 1.08 (95% CI 1.006 to 1.16)) for LRI. The weekly URI incidence peaked in May–June and was significantly associated with lags in weekly URI incidence and the average humidity, rainfall and water level. The weekly LRI incidence exhibited significant seasonality (P<0.0001), with an annual peak in September–October and was significantly associated with lags in weekly LRI incidence and lags in weekly average temperature, rainfall and water level. CONCLUSIONS: ARIs are a leading cause of childhood hospitalisation in HCMC, Vietnam. The incidence of ARIs was higher in the wet season and in specific HCMC districts. These results may guide health authorities in where and when to effectively allocate resources for the prevention and control of ARIs.",2018 Jan 21,"['Ho, Nhan Thi', 'Thompson, Corinne', 'Nhan, Le Nguyen Thanh', 'Van, Hoang Minh Tu', 'Dung, Nguyen Thanh', 'Tran My, Phuc', 'Quang, Vo Minh', 'Minh, Ngo Ngoc Quang', 'Tuan, Tran Anh', 'Hung, Nguyen Thanh', 'Tuan, Ha Manh', 'Vinh Chau, Nguyen Van', 'Wolbers, Marcel', 'Thwaites, Guy E', 'Choisy, Marc', 'Baker, Stephen']",BMJ Open,,,True
3702eb1540a20656d1f723b180c1a8607c6cb4a6,PMC,Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus,http://dx.doi.org/10.1128/mSystems.00135-17,PMC5781259,29404423,CC BY,"Comprehensive knowledge of host-pathogen interactions is central to understand the life cycle of a pathogen and devise specific therapeutic strategies. Protein-protein interactions (PPIs) are key mediators of host-pathogen interactions. Hepatitis E virus (HEV) is a major cause of viral hepatitis in humans. Recent reports also demonstrate its extrahepatic manifestations in the brain. Toward understanding the molecular details of HEV life cycle, we screened human liver and fetal brain cDNA libraries to identify the host interaction partners of proteins encoded by genotype 1 HEV and constructed the virus-host PPI network. Analysis of the network indicated a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed the presence of multiple host translation regulatory factors in the viral translation/replication complex. Depletion of host translation factors such as eIF4A2, eIF3A, and RACK1 significantly reduced the viral replication, whereas eIF2AK4 depletion had no effect. These findings highlight the ingenuity of the pathogen in manipulating the host machinery to its own benefit, a clear understanding of which is essential for the identification of strategic targets and development of specific antivirals against HEV. IMPORTANCE Hepatitis E virus (HEV) is a pathogen that is transmitted by the fecal-oral route. Owing to the lack of an efficient laboratory model, the life cycle of the virus is poorly understood. During the course of infection, interactions between the viral and host proteins play essential roles, a clear understanding of which is essential to decode the life cycle of the virus. In this study, we identified the direct host interaction partners of all HEV proteins and generated a PPI network. Our functional analysis of the HEV-human PPI network reveals a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed an essential role of several host factors in HEV replication. Collectively, the results from our study provide a vast resource of PPI data from HEV and its human host and identify the molecular components of the viral translation/replication machinery.",2018 Jan 23,"['Subramani, Chandru', 'Nair, Vidya P.', 'Anang, Saumya', 'Mandal, Sukhen Das', 'Pareek, Madhu', 'Kaushik, Nidhi', 'Srivastava, Akriti', 'Saha, Sudipto', 'Shalimar,', 'Nayak, Baibaswata', 'Ranjith-Kumar, C. T.', 'Surjit, Milan']",mSystems,,,True
2eed207a21431cbb824751318ec71055a3e3e8a7,PMC,Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus,http://dx.doi.org/10.1128/mSystems.00135-17,PMC5781259,29404423,CC BY,"Comprehensive knowledge of host-pathogen interactions is central to understand the life cycle of a pathogen and devise specific therapeutic strategies. Protein-protein interactions (PPIs) are key mediators of host-pathogen interactions. Hepatitis E virus (HEV) is a major cause of viral hepatitis in humans. Recent reports also demonstrate its extrahepatic manifestations in the brain. Toward understanding the molecular details of HEV life cycle, we screened human liver and fetal brain cDNA libraries to identify the host interaction partners of proteins encoded by genotype 1 HEV and constructed the virus-host PPI network. Analysis of the network indicated a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed the presence of multiple host translation regulatory factors in the viral translation/replication complex. Depletion of host translation factors such as eIF4A2, eIF3A, and RACK1 significantly reduced the viral replication, whereas eIF2AK4 depletion had no effect. These findings highlight the ingenuity of the pathogen in manipulating the host machinery to its own benefit, a clear understanding of which is essential for the identification of strategic targets and development of specific antivirals against HEV. IMPORTANCE Hepatitis E virus (HEV) is a pathogen that is transmitted by the fecal-oral route. Owing to the lack of an efficient laboratory model, the life cycle of the virus is poorly understood. During the course of infection, interactions between the viral and host proteins play essential roles, a clear understanding of which is essential to decode the life cycle of the virus. In this study, we identified the direct host interaction partners of all HEV proteins and generated a PPI network. Our functional analysis of the HEV-human PPI network reveals a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed an essential role of several host factors in HEV replication. Collectively, the results from our study provide a vast resource of PPI data from HEV and its human host and identify the molecular components of the viral translation/replication machinery.",2018 Jan 23,"['Subramani, Chandru', 'Nair, Vidya P.', 'Anang, Saumya', 'Mandal, Sukhen Das', 'Pareek, Madhu', 'Kaushik, Nidhi', 'Srivastava, Akriti', 'Saha, Sudipto', 'Shalimar,', 'Nayak, Baibaswata', 'Ranjith-Kumar, C. T.', 'Surjit, Milan']",mSystems,,,False
a91c40470eb10552ba113938724543f04c5dfb57,PMC,Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus,http://dx.doi.org/10.1128/mSystems.00135-17,PMC5781259,29404423,CC BY,"Comprehensive knowledge of host-pathogen interactions is central to understand the life cycle of a pathogen and devise specific therapeutic strategies. Protein-protein interactions (PPIs) are key mediators of host-pathogen interactions. Hepatitis E virus (HEV) is a major cause of viral hepatitis in humans. Recent reports also demonstrate its extrahepatic manifestations in the brain. Toward understanding the molecular details of HEV life cycle, we screened human liver and fetal brain cDNA libraries to identify the host interaction partners of proteins encoded by genotype 1 HEV and constructed the virus-host PPI network. Analysis of the network indicated a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed the presence of multiple host translation regulatory factors in the viral translation/replication complex. Depletion of host translation factors such as eIF4A2, eIF3A, and RACK1 significantly reduced the viral replication, whereas eIF2AK4 depletion had no effect. These findings highlight the ingenuity of the pathogen in manipulating the host machinery to its own benefit, a clear understanding of which is essential for the identification of strategic targets and development of specific antivirals against HEV. IMPORTANCE Hepatitis E virus (HEV) is a pathogen that is transmitted by the fecal-oral route. Owing to the lack of an efficient laboratory model, the life cycle of the virus is poorly understood. During the course of infection, interactions between the viral and host proteins play essential roles, a clear understanding of which is essential to decode the life cycle of the virus. In this study, we identified the direct host interaction partners of all HEV proteins and generated a PPI network. Our functional analysis of the HEV-human PPI network reveals a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed an essential role of several host factors in HEV replication. Collectively, the results from our study provide a vast resource of PPI data from HEV and its human host and identify the molecular components of the viral translation/replication machinery.",2018 Jan 23,"['Subramani, Chandru', 'Nair, Vidya P.', 'Anang, Saumya', 'Mandal, Sukhen Das', 'Pareek, Madhu', 'Kaushik, Nidhi', 'Srivastava, Akriti', 'Saha, Sudipto', 'Shalimar,', 'Nayak, Baibaswata', 'Ranjith-Kumar, C. T.', 'Surjit, Milan']",mSystems,,,False
313b0c53c4c974bf5cf99c3a53729fb787c15992,PMC,Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus,http://dx.doi.org/10.1128/mSystems.00135-17,PMC5781259,29404423,CC BY,"Comprehensive knowledge of host-pathogen interactions is central to understand the life cycle of a pathogen and devise specific therapeutic strategies. Protein-protein interactions (PPIs) are key mediators of host-pathogen interactions. Hepatitis E virus (HEV) is a major cause of viral hepatitis in humans. Recent reports also demonstrate its extrahepatic manifestations in the brain. Toward understanding the molecular details of HEV life cycle, we screened human liver and fetal brain cDNA libraries to identify the host interaction partners of proteins encoded by genotype 1 HEV and constructed the virus-host PPI network. Analysis of the network indicated a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed the presence of multiple host translation regulatory factors in the viral translation/replication complex. Depletion of host translation factors such as eIF4A2, eIF3A, and RACK1 significantly reduced the viral replication, whereas eIF2AK4 depletion had no effect. These findings highlight the ingenuity of the pathogen in manipulating the host machinery to its own benefit, a clear understanding of which is essential for the identification of strategic targets and development of specific antivirals against HEV. IMPORTANCE Hepatitis E virus (HEV) is a pathogen that is transmitted by the fecal-oral route. Owing to the lack of an efficient laboratory model, the life cycle of the virus is poorly understood. During the course of infection, interactions between the viral and host proteins play essential roles, a clear understanding of which is essential to decode the life cycle of the virus. In this study, we identified the direct host interaction partners of all HEV proteins and generated a PPI network. Our functional analysis of the HEV-human PPI network reveals a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed an essential role of several host factors in HEV replication. Collectively, the results from our study provide a vast resource of PPI data from HEV and its human host and identify the molecular components of the viral translation/replication machinery.",2018 Jan 23,"['Subramani, Chandru', 'Nair, Vidya P.', 'Anang, Saumya', 'Mandal, Sukhen Das', 'Pareek, Madhu', 'Kaushik, Nidhi', 'Srivastava, Akriti', 'Saha, Sudipto', 'Shalimar,', 'Nayak, Baibaswata', 'Ranjith-Kumar, C. T.', 'Surjit, Milan']",mSystems,,,False
8079f3267c8e4f034733080fda9a26f235fedcdd,PMC,Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus,http://dx.doi.org/10.1128/mSystems.00135-17,PMC5781259,29404423,CC BY,"Comprehensive knowledge of host-pathogen interactions is central to understand the life cycle of a pathogen and devise specific therapeutic strategies. Protein-protein interactions (PPIs) are key mediators of host-pathogen interactions. Hepatitis E virus (HEV) is a major cause of viral hepatitis in humans. Recent reports also demonstrate its extrahepatic manifestations in the brain. Toward understanding the molecular details of HEV life cycle, we screened human liver and fetal brain cDNA libraries to identify the host interaction partners of proteins encoded by genotype 1 HEV and constructed the virus-host PPI network. Analysis of the network indicated a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed the presence of multiple host translation regulatory factors in the viral translation/replication complex. Depletion of host translation factors such as eIF4A2, eIF3A, and RACK1 significantly reduced the viral replication, whereas eIF2AK4 depletion had no effect. These findings highlight the ingenuity of the pathogen in manipulating the host machinery to its own benefit, a clear understanding of which is essential for the identification of strategic targets and development of specific antivirals against HEV. IMPORTANCE Hepatitis E virus (HEV) is a pathogen that is transmitted by the fecal-oral route. Owing to the lack of an efficient laboratory model, the life cycle of the virus is poorly understood. During the course of infection, interactions between the viral and host proteins play essential roles, a clear understanding of which is essential to decode the life cycle of the virus. In this study, we identified the direct host interaction partners of all HEV proteins and generated a PPI network. Our functional analysis of the HEV-human PPI network reveals a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed an essential role of several host factors in HEV replication. Collectively, the results from our study provide a vast resource of PPI data from HEV and its human host and identify the molecular components of the viral translation/replication machinery.",2018 Jan 23,"['Subramani, Chandru', 'Nair, Vidya P.', 'Anang, Saumya', 'Mandal, Sukhen Das', 'Pareek, Madhu', 'Kaushik, Nidhi', 'Srivastava, Akriti', 'Saha, Sudipto', 'Shalimar,', 'Nayak, Baibaswata', 'Ranjith-Kumar, C. T.', 'Surjit, Milan']",mSystems,,,False
d1ba39cb16407a72fac15d0bb30d6a9cd02402dd,PMC,Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus,http://dx.doi.org/10.1128/mSystems.00135-17,PMC5781259,29404423,CC BY,"Comprehensive knowledge of host-pathogen interactions is central to understand the life cycle of a pathogen and devise specific therapeutic strategies. Protein-protein interactions (PPIs) are key mediators of host-pathogen interactions. Hepatitis E virus (HEV) is a major cause of viral hepatitis in humans. Recent reports also demonstrate its extrahepatic manifestations in the brain. Toward understanding the molecular details of HEV life cycle, we screened human liver and fetal brain cDNA libraries to identify the host interaction partners of proteins encoded by genotype 1 HEV and constructed the virus-host PPI network. Analysis of the network indicated a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed the presence of multiple host translation regulatory factors in the viral translation/replication complex. Depletion of host translation factors such as eIF4A2, eIF3A, and RACK1 significantly reduced the viral replication, whereas eIF2AK4 depletion had no effect. These findings highlight the ingenuity of the pathogen in manipulating the host machinery to its own benefit, a clear understanding of which is essential for the identification of strategic targets and development of specific antivirals against HEV. IMPORTANCE Hepatitis E virus (HEV) is a pathogen that is transmitted by the fecal-oral route. Owing to the lack of an efficient laboratory model, the life cycle of the virus is poorly understood. During the course of infection, interactions between the viral and host proteins play essential roles, a clear understanding of which is essential to decode the life cycle of the virus. In this study, we identified the direct host interaction partners of all HEV proteins and generated a PPI network. Our functional analysis of the HEV-human PPI network reveals a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed an essential role of several host factors in HEV replication. Collectively, the results from our study provide a vast resource of PPI data from HEV and its human host and identify the molecular components of the viral translation/replication machinery.",2018 Jan 23,"['Subramani, Chandru', 'Nair, Vidya P.', 'Anang, Saumya', 'Mandal, Sukhen Das', 'Pareek, Madhu', 'Kaushik, Nidhi', 'Srivastava, Akriti', 'Saha, Sudipto', 'Shalimar,', 'Nayak, Baibaswata', 'Ranjith-Kumar, C. T.', 'Surjit, Milan']",mSystems,,,False
622f38ef44c2b61d746620b03b5d4480aec931dd,PMC,Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus,http://dx.doi.org/10.1128/mSystems.00135-17,PMC5781259,29404423,CC BY,"Comprehensive knowledge of host-pathogen interactions is central to understand the life cycle of a pathogen and devise specific therapeutic strategies. Protein-protein interactions (PPIs) are key mediators of host-pathogen interactions. Hepatitis E virus (HEV) is a major cause of viral hepatitis in humans. Recent reports also demonstrate its extrahepatic manifestations in the brain. Toward understanding the molecular details of HEV life cycle, we screened human liver and fetal brain cDNA libraries to identify the host interaction partners of proteins encoded by genotype 1 HEV and constructed the virus-host PPI network. Analysis of the network indicated a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed the presence of multiple host translation regulatory factors in the viral translation/replication complex. Depletion of host translation factors such as eIF4A2, eIF3A, and RACK1 significantly reduced the viral replication, whereas eIF2AK4 depletion had no effect. These findings highlight the ingenuity of the pathogen in manipulating the host machinery to its own benefit, a clear understanding of which is essential for the identification of strategic targets and development of specific antivirals against HEV. IMPORTANCE Hepatitis E virus (HEV) is a pathogen that is transmitted by the fecal-oral route. Owing to the lack of an efficient laboratory model, the life cycle of the virus is poorly understood. During the course of infection, interactions between the viral and host proteins play essential roles, a clear understanding of which is essential to decode the life cycle of the virus. In this study, we identified the direct host interaction partners of all HEV proteins and generated a PPI network. Our functional analysis of the HEV-human PPI network reveals a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed an essential role of several host factors in HEV replication. Collectively, the results from our study provide a vast resource of PPI data from HEV and its human host and identify the molecular components of the viral translation/replication machinery.",2018 Jan 23,"['Subramani, Chandru', 'Nair, Vidya P.', 'Anang, Saumya', 'Mandal, Sukhen Das', 'Pareek, Madhu', 'Kaushik, Nidhi', 'Srivastava, Akriti', 'Saha, Sudipto', 'Shalimar,', 'Nayak, Baibaswata', 'Ranjith-Kumar, C. T.', 'Surjit, Milan']",mSystems,,,False
7173c0b2dec6dea33c883abf933ebc5fecccc320,PMC,Evidence of porcine epidemic diarrhea virus (PEDV) shedding in semen from infected specific pathogen-free boars,http://dx.doi.org/10.1186/s13567-018-0505-2,PMC5784731,29368629,CC BY,"In 2013, PED emerged for the first time in the United States (US). The porcine epidemic diarrhea virus (PEDV) spread quickly throughout North America. Infection with PEDV causes watery diarrhea and up to 100% mortality in piglets, particularly for highly pathogenic non-InDel strains circulating in the US. PEDV is mainly transmitted by the fecal–oral route. Transmission via the venereal route has been suspected but not previously investigated. The aim of the study was to determine if PEDV could be detected in semen from infected specific pathogen-free (SPF) boars inoculated with a PEDV US non-InDel strain suggesting venereal transmission may occur. Two boars orally inoculated with PEDV showed clinical signs and virus shedding in feces. Transient presence of the PEDV genome was detected by RT-qPCR in the seminal (5.06 × 10(2) to 2.44 × 10(3) genomic copies/mL) and sperm-rich fraction of semen (5.64 × 10(2) to 3.40 × 10(4) genomic copies/mL) and a longer duration of viral shedding was observed in the sperm-rich fraction. The evidence of PEDV shedding in semen raises new questions in term of disease spread within the pig population with the use of potentially contaminated semen.",2018 Jan 24,"['Gallien, Sarah', 'Moro, Angélique', 'Lediguerher, Gérald', 'Catinot, Virginie', 'Paboeuf, Frédéric', 'Bigault, Lionel', 'Berri, Mustapha', 'Gauger, Phillip C.', 'Pozzi, Nathalie', 'Authié, Edith', 'Rose, Nicolas', 'Grasland, Béatrice']",Vet Res,,,True
93d7989c46a48482600c23e05c2594c4c7465ba6,PMC,Lab-Attenuated Rabies Virus Causes Abortive Infection and Induces Cytokine Expression in Astrocytes by Activating Mitochondrial Antiviral-Signaling Protein Signaling Pathway,http://dx.doi.org/10.3389/fimmu.2017.02011,PMC5785723,29403485,CC BY,"Rabies is an ancient disease but remains endemic in most parts of the world and causes approximately 59,000 deaths annually. The mechanism through which the causative agent, rabies virus (RABV), evades the host immune response and infects the host central nervous system (CNS) has not been completely elucidated thus far. Our previous studies have shown that lab-attenuated, but not wild-type (wt), RABV activates the innate immune response in the mouse and dog models. In this present study, we demonstrate that lab-attenuated RABV causes abortive infection in astrocytes, the most abundant glial cells in the CNS. Furthermore, we found that lab-attenuated RABV produces more double-stranded RNA (dsRNA) than wt RABV, which is recognized by retinoic acid-inducible gene I (RIG-I) or melanoma differentiation-associated protein 5 (MDA5). Activation of mitochondrial antiviral-signaling protein (MAVS), the common adaptor molecule for RIG-I and MDA5, results in the production of type I interferon (IFN) and the expression of hundreds of IFN-stimulated genes, which suppress RABV replication and spread in astrocytes. Notably, lab-attenuated RABV replicates in a manner identical to that of wt RABV in MAVS−/− astrocytes. It was also found that lab-attenuated, but not wt, RABV induces the expression of inflammatory cytokines via the MAVS- p38/NF-κB signaling pathway. These inflammatory cytokines increase the blood–brain barrier permeability and thus enable immune cells and antibodies infiltrate the CNS parenchyma, resulting in RABV control and elimination. In contrast, wt RABV restricts dsRNA production and thus evades innate recognition by RIG-I/MDA5 in astrocytes, which could be one of the mechanisms by which wt RABV evades the host immune response in resident CNS cells. Our findings suggest that astrocytes play a critical role in limiting the replication of lab-attenuated RABV in the CNS.",2018 Jan 19,"['Tian, Bin', 'Zhou, Ming', 'Yang, Yu', 'Yu, Lan', 'Luo, Zhaochen', 'Tian, Dayong', 'Wang, Ke', 'Cui, Min', 'Chen, Huanchun', 'Fu, Zhen F.', 'Zhao, Ling']",Front Immunol,,,True
9be783afc22075545d893250f5c7f1ef7317cf37,PMC,SWOT analysis and revelation in traditional Chinese medicine internationalization,http://dx.doi.org/10.1186/s13020-018-0165-1,PMC5785906,29416556,CC BY,"Traditional Chinese medicine (TCM) is currently the best-preserved and most influential traditional medical system with the largest number of users worldwide. In recent years, the trend of TCM adoption has increased greatly, but the process of TCM internationalization has suffered from a series of setbacks for both internal and external reasons. Thus, the process of TCM internationalization faces formidable challenges, although it also has favourable opportunities. Using SWOT analysis, this paper investigates the strengths, weaknesses, opportunities and threats for TCM. These findings can serve as references for TCM enterprises with global ambitions.",2018 Jan 25,"['Tang, Haitao', 'Huang, Wenlong', 'Ma, Jimei', 'Liu, Li']",Chin Med,,,True
9a2a9e22d45a0bf24645251b61171f93766cfc4d,PMC,Cerebrospinal fluid chemokine patterns in children with enterovirus 71-related encephalitis,http://dx.doi.org/10.1038/s41598-018-19988-6,PMC5786096,29374213,CC BY,"Enterovirus 71 (EV71) is a major pathogen that causes hand, foot and mouth disease (HFMD) as well as neurological complications, such as encephalitis. The chemokines involved in the migration of leukocytes have increasingly been implicated in infectious diseases of the central nervous system. Few studies have evaluated the levels of chemokines in HMFD children with EV71-related encephalitis. In the present study, we evaluated the cerebrospinal fluid (CSF) levels of the chemokines IL-8, RANTES, MIG, MCP-1 and IP-10 in 99 children with EV71-related encephalitis and 22 children with febrile convulsion (FC). We found that the concentrations of IL-8, RANTES, MIG and IP-10 were significantly higher in HFMD children with encephalitis compared to patients with FC. Additionally, these four chemokines were dramatically reduced during convalescence. Inversely, the level of MCP-1 was lower in encephalitis patients than FC patients and was not significantly reduced during convalescence. Additionally, MIG was strongly correlated with IP-10 in encephalitis patients. Furthermore, the area under the ROC curve (AUC) of CSF MIG and IP-10 in distinguishing encephalitis from FC were 0.869 and 0.876, and the corresponding sensitivities/specificities were 67.7%/100.0% and 67.7%/95.5%, respectively. In conclusion, our results indicate that chemokines play important roles in the pathogenesis of EV71 infection.",2018 Jan 26,"['Liu, Jinling', 'Li, Shuxian', 'Cai, Chunyan', 'Xu, Yingchun', 'Jiang, Yuan', 'Chen, Zhimin']",Sci Rep,,,False
db12f0dcf2d4d913668f70ce1848c37ae2f31c69,PMC,Cerebrospinal fluid chemokine patterns in children with enterovirus 71-related encephalitis,http://dx.doi.org/10.1038/s41598-018-19988-6,PMC5786096,29374213,CC BY,"Enterovirus 71 (EV71) is a major pathogen that causes hand, foot and mouth disease (HFMD) as well as neurological complications, such as encephalitis. The chemokines involved in the migration of leukocytes have increasingly been implicated in infectious diseases of the central nervous system. Few studies have evaluated the levels of chemokines in HMFD children with EV71-related encephalitis. In the present study, we evaluated the cerebrospinal fluid (CSF) levels of the chemokines IL-8, RANTES, MIG, MCP-1 and IP-10 in 99 children with EV71-related encephalitis and 22 children with febrile convulsion (FC). We found that the concentrations of IL-8, RANTES, MIG and IP-10 were significantly higher in HFMD children with encephalitis compared to patients with FC. Additionally, these four chemokines were dramatically reduced during convalescence. Inversely, the level of MCP-1 was lower in encephalitis patients than FC patients and was not significantly reduced during convalescence. Additionally, MIG was strongly correlated with IP-10 in encephalitis patients. Furthermore, the area under the ROC curve (AUC) of CSF MIG and IP-10 in distinguishing encephalitis from FC were 0.869 and 0.876, and the corresponding sensitivities/specificities were 67.7%/100.0% and 67.7%/95.5%, respectively. In conclusion, our results indicate that chemokines play important roles in the pathogenesis of EV71 infection.",2018 Jan 26,"['Liu, Jinling', 'Li, Shuxian', 'Cai, Chunyan', 'Xu, Yingchun', 'Jiang, Yuan', 'Chen, Zhimin']",Sci Rep,,,True
cbf9753177215fea032ae9f8193ce6a0380876e8,PMC,Transcriptional changes detected in fecal RNA of neonatal dairy calves undergoing a mild diarrhea are associated with inflammatory biomarkers,http://dx.doi.org/10.1371/journal.pone.0191599,PMC5786293,29373601,CC BY,"After birth, a newborn calf has to adapt to an extrauterine life characterized by several physiological changes. In particular, maturation of the gastrointestinal tract in a new environment loaded with potential pathogens, which can predispose neonatal calves to develop diarrhea, and is a major cause of morbidity and mortality during the first 4 wks of life. We aimed to investigate the inflammatory adaptations at a transcriptomic level in the gastrointestinal (GI) tract to a mild diarrhea in neonatal dairy calves using RNA isolated from fresh fecal samples. Eight newborn Jersey male calves were used from birth to 5 wks of age and housed in individual pens. After birth, calves received 1.9 L of colostrum from their respective dams. Calves had ad-libitum access to water and starter grain (22% CP) and were fed twice daily a total of 5.6 L pasteurized whole milk. Starter intake, body weight (BW), fecal score, withers height (WH), and rectal temperature (RT) were recorded throughout the experiment. Blood samples were collected weekly for metabolic and inflammatory profiling from wk 0 to wk 5. Fresh fecal samples were collected weekly and immediately flash frozen until RNA was extracted using a Trizol-based method, and subsequently, an RT-qPCR analysis was performed. Orthogonal contrasts were used to evaluate linear or quadratic effects over time. Starter intake, BW, and WH increased over time. Fecal score was greatest (2.6 ± 0.3) during wk 2. The concentrations of IL-6, ceruloplasmin, and haptoglobin had a positive quadratic effect with maximal concentrations during wk 2, which corresponded to the maximal fecal score observed during the same time. The concentration of serum amyloid A decreased over time. The mRNA expression of the proinflammatory related genes TLR4, TNFA, IL8, and IL1B had a positive quadratic effect of time. A time effect was observed for the cell membrane sodium-dependent glucose transporter SLC5A1, for the major carbohydrate facilitated transporter SLC2A2, and water transport function AQP3, where SLC5A1 and AQP3 had a negative quadratic effect over time. Our data support the use of the fecal RNA as a noninvasive tool to investigate intestinal transcriptomic profiling of dairy calves experiencing diarrhea, which would be advantageous for future research including nutritional effects and health conditions.",2018 Jan 26,"['Rosa, Fernanda', 'Busato, Sebastiano', 'Avaroma, Fatima C.', 'Linville, Kali', 'Trevisi, Erminio', 'Osorio, Johan S.', 'Bionaz, Massimo']",PLoS One,,,True
63220a877a5e47bb03c0022cd2a5ae5ec0831c2b,PMC,Transcriptional changes detected in fecal RNA of neonatal dairy calves undergoing a mild diarrhea are associated with inflammatory biomarkers,http://dx.doi.org/10.1371/journal.pone.0191599,PMC5786293,29373601,CC BY,"After birth, a newborn calf has to adapt to an extrauterine life characterized by several physiological changes. In particular, maturation of the gastrointestinal tract in a new environment loaded with potential pathogens, which can predispose neonatal calves to develop diarrhea, and is a major cause of morbidity and mortality during the first 4 wks of life. We aimed to investigate the inflammatory adaptations at a transcriptomic level in the gastrointestinal (GI) tract to a mild diarrhea in neonatal dairy calves using RNA isolated from fresh fecal samples. Eight newborn Jersey male calves were used from birth to 5 wks of age and housed in individual pens. After birth, calves received 1.9 L of colostrum from their respective dams. Calves had ad-libitum access to water and starter grain (22% CP) and were fed twice daily a total of 5.6 L pasteurized whole milk. Starter intake, body weight (BW), fecal score, withers height (WH), and rectal temperature (RT) were recorded throughout the experiment. Blood samples were collected weekly for metabolic and inflammatory profiling from wk 0 to wk 5. Fresh fecal samples were collected weekly and immediately flash frozen until RNA was extracted using a Trizol-based method, and subsequently, an RT-qPCR analysis was performed. Orthogonal contrasts were used to evaluate linear or quadratic effects over time. Starter intake, BW, and WH increased over time. Fecal score was greatest (2.6 ± 0.3) during wk 2. The concentrations of IL-6, ceruloplasmin, and haptoglobin had a positive quadratic effect with maximal concentrations during wk 2, which corresponded to the maximal fecal score observed during the same time. The concentration of serum amyloid A decreased over time. The mRNA expression of the proinflammatory related genes TLR4, TNFA, IL8, and IL1B had a positive quadratic effect of time. A time effect was observed for the cell membrane sodium-dependent glucose transporter SLC5A1, for the major carbohydrate facilitated transporter SLC2A2, and water transport function AQP3, where SLC5A1 and AQP3 had a negative quadratic effect over time. Our data support the use of the fecal RNA as a noninvasive tool to investigate intestinal transcriptomic profiling of dairy calves experiencing diarrhea, which would be advantageous for future research including nutritional effects and health conditions.",2018 Jan 26,"['Rosa, Fernanda', 'Busato, Sebastiano', 'Avaroma, Fatima C.', 'Linville, Kali', 'Trevisi, Erminio', 'Osorio, Johan S.', 'Bionaz, Massimo']",PLoS One,,,False
56e43b27f6f97b8ece461abfab34d330b5ddd031,PMC,Transcriptional changes detected in fecal RNA of neonatal dairy calves undergoing a mild diarrhea are associated with inflammatory biomarkers,http://dx.doi.org/10.1371/journal.pone.0191599,PMC5786293,29373601,CC BY,"After birth, a newborn calf has to adapt to an extrauterine life characterized by several physiological changes. In particular, maturation of the gastrointestinal tract in a new environment loaded with potential pathogens, which can predispose neonatal calves to develop diarrhea, and is a major cause of morbidity and mortality during the first 4 wks of life. We aimed to investigate the inflammatory adaptations at a transcriptomic level in the gastrointestinal (GI) tract to a mild diarrhea in neonatal dairy calves using RNA isolated from fresh fecal samples. Eight newborn Jersey male calves were used from birth to 5 wks of age and housed in individual pens. After birth, calves received 1.9 L of colostrum from their respective dams. Calves had ad-libitum access to water and starter grain (22% CP) and were fed twice daily a total of 5.6 L pasteurized whole milk. Starter intake, body weight (BW), fecal score, withers height (WH), and rectal temperature (RT) were recorded throughout the experiment. Blood samples were collected weekly for metabolic and inflammatory profiling from wk 0 to wk 5. Fresh fecal samples were collected weekly and immediately flash frozen until RNA was extracted using a Trizol-based method, and subsequently, an RT-qPCR analysis was performed. Orthogonal contrasts were used to evaluate linear or quadratic effects over time. Starter intake, BW, and WH increased over time. Fecal score was greatest (2.6 ± 0.3) during wk 2. The concentrations of IL-6, ceruloplasmin, and haptoglobin had a positive quadratic effect with maximal concentrations during wk 2, which corresponded to the maximal fecal score observed during the same time. The concentration of serum amyloid A decreased over time. The mRNA expression of the proinflammatory related genes TLR4, TNFA, IL8, and IL1B had a positive quadratic effect of time. A time effect was observed for the cell membrane sodium-dependent glucose transporter SLC5A1, for the major carbohydrate facilitated transporter SLC2A2, and water transport function AQP3, where SLC5A1 and AQP3 had a negative quadratic effect over time. Our data support the use of the fecal RNA as a noninvasive tool to investigate intestinal transcriptomic profiling of dairy calves experiencing diarrhea, which would be advantageous for future research including nutritional effects and health conditions.",2018 Jan 26,"['Rosa, Fernanda', 'Busato, Sebastiano', 'Avaroma, Fatima C.', 'Linville, Kali', 'Trevisi, Erminio', 'Osorio, Johan S.', 'Bionaz, Massimo']",PLoS One,,,False
fca1fd31f59808311418169e4e7006e3aa518b0a,PMC,Transcriptional changes detected in fecal RNA of neonatal dairy calves undergoing a mild diarrhea are associated with inflammatory biomarkers,http://dx.doi.org/10.1371/journal.pone.0191599,PMC5786293,29373601,CC BY,"After birth, a newborn calf has to adapt to an extrauterine life characterized by several physiological changes. In particular, maturation of the gastrointestinal tract in a new environment loaded with potential pathogens, which can predispose neonatal calves to develop diarrhea, and is a major cause of morbidity and mortality during the first 4 wks of life. We aimed to investigate the inflammatory adaptations at a transcriptomic level in the gastrointestinal (GI) tract to a mild diarrhea in neonatal dairy calves using RNA isolated from fresh fecal samples. Eight newborn Jersey male calves were used from birth to 5 wks of age and housed in individual pens. After birth, calves received 1.9 L of colostrum from their respective dams. Calves had ad-libitum access to water and starter grain (22% CP) and were fed twice daily a total of 5.6 L pasteurized whole milk. Starter intake, body weight (BW), fecal score, withers height (WH), and rectal temperature (RT) were recorded throughout the experiment. Blood samples were collected weekly for metabolic and inflammatory profiling from wk 0 to wk 5. Fresh fecal samples were collected weekly and immediately flash frozen until RNA was extracted using a Trizol-based method, and subsequently, an RT-qPCR analysis was performed. Orthogonal contrasts were used to evaluate linear or quadratic effects over time. Starter intake, BW, and WH increased over time. Fecal score was greatest (2.6 ± 0.3) during wk 2. The concentrations of IL-6, ceruloplasmin, and haptoglobin had a positive quadratic effect with maximal concentrations during wk 2, which corresponded to the maximal fecal score observed during the same time. The concentration of serum amyloid A decreased over time. The mRNA expression of the proinflammatory related genes TLR4, TNFA, IL8, and IL1B had a positive quadratic effect of time. A time effect was observed for the cell membrane sodium-dependent glucose transporter SLC5A1, for the major carbohydrate facilitated transporter SLC2A2, and water transport function AQP3, where SLC5A1 and AQP3 had a negative quadratic effect over time. Our data support the use of the fecal RNA as a noninvasive tool to investigate intestinal transcriptomic profiling of dairy calves experiencing diarrhea, which would be advantageous for future research including nutritional effects and health conditions.",2018 Jan 26,"['Rosa, Fernanda', 'Busato, Sebastiano', 'Avaroma, Fatima C.', 'Linville, Kali', 'Trevisi, Erminio', 'Osorio, Johan S.', 'Bionaz, Massimo']",PLoS One,,,False
d10bcd18a42cdd4980ca13114ca8994dc1a31c13,PMC,Transcriptional changes detected in fecal RNA of neonatal dairy calves undergoing a mild diarrhea are associated with inflammatory biomarkers,http://dx.doi.org/10.1371/journal.pone.0191599,PMC5786293,29373601,CC BY,"After birth, a newborn calf has to adapt to an extrauterine life characterized by several physiological changes. In particular, maturation of the gastrointestinal tract in a new environment loaded with potential pathogens, which can predispose neonatal calves to develop diarrhea, and is a major cause of morbidity and mortality during the first 4 wks of life. We aimed to investigate the inflammatory adaptations at a transcriptomic level in the gastrointestinal (GI) tract to a mild diarrhea in neonatal dairy calves using RNA isolated from fresh fecal samples. Eight newborn Jersey male calves were used from birth to 5 wks of age and housed in individual pens. After birth, calves received 1.9 L of colostrum from their respective dams. Calves had ad-libitum access to water and starter grain (22% CP) and were fed twice daily a total of 5.6 L pasteurized whole milk. Starter intake, body weight (BW), fecal score, withers height (WH), and rectal temperature (RT) were recorded throughout the experiment. Blood samples were collected weekly for metabolic and inflammatory profiling from wk 0 to wk 5. Fresh fecal samples were collected weekly and immediately flash frozen until RNA was extracted using a Trizol-based method, and subsequently, an RT-qPCR analysis was performed. Orthogonal contrasts were used to evaluate linear or quadratic effects over time. Starter intake, BW, and WH increased over time. Fecal score was greatest (2.6 ± 0.3) during wk 2. The concentrations of IL-6, ceruloplasmin, and haptoglobin had a positive quadratic effect with maximal concentrations during wk 2, which corresponded to the maximal fecal score observed during the same time. The concentration of serum amyloid A decreased over time. The mRNA expression of the proinflammatory related genes TLR4, TNFA, IL8, and IL1B had a positive quadratic effect of time. A time effect was observed for the cell membrane sodium-dependent glucose transporter SLC5A1, for the major carbohydrate facilitated transporter SLC2A2, and water transport function AQP3, where SLC5A1 and AQP3 had a negative quadratic effect over time. Our data support the use of the fecal RNA as a noninvasive tool to investigate intestinal transcriptomic profiling of dairy calves experiencing diarrhea, which would be advantageous for future research including nutritional effects and health conditions.",2018 Jan 26,"['Rosa, Fernanda', 'Busato, Sebastiano', 'Avaroma, Fatima C.', 'Linville, Kali', 'Trevisi, Erminio', 'Osorio, Johan S.', 'Bionaz, Massimo']",PLoS One,,,False
958c3c58c3b6489df44b2a85fbfcab80c9ed6b81,PMC,Transcriptional changes detected in fecal RNA of neonatal dairy calves undergoing a mild diarrhea are associated with inflammatory biomarkers,http://dx.doi.org/10.1371/journal.pone.0191599,PMC5786293,29373601,CC BY,"After birth, a newborn calf has to adapt to an extrauterine life characterized by several physiological changes. In particular, maturation of the gastrointestinal tract in a new environment loaded with potential pathogens, which can predispose neonatal calves to develop diarrhea, and is a major cause of morbidity and mortality during the first 4 wks of life. We aimed to investigate the inflammatory adaptations at a transcriptomic level in the gastrointestinal (GI) tract to a mild diarrhea in neonatal dairy calves using RNA isolated from fresh fecal samples. Eight newborn Jersey male calves were used from birth to 5 wks of age and housed in individual pens. After birth, calves received 1.9 L of colostrum from their respective dams. Calves had ad-libitum access to water and starter grain (22% CP) and were fed twice daily a total of 5.6 L pasteurized whole milk. Starter intake, body weight (BW), fecal score, withers height (WH), and rectal temperature (RT) were recorded throughout the experiment. Blood samples were collected weekly for metabolic and inflammatory profiling from wk 0 to wk 5. Fresh fecal samples were collected weekly and immediately flash frozen until RNA was extracted using a Trizol-based method, and subsequently, an RT-qPCR analysis was performed. Orthogonal contrasts were used to evaluate linear or quadratic effects over time. Starter intake, BW, and WH increased over time. Fecal score was greatest (2.6 ± 0.3) during wk 2. The concentrations of IL-6, ceruloplasmin, and haptoglobin had a positive quadratic effect with maximal concentrations during wk 2, which corresponded to the maximal fecal score observed during the same time. The concentration of serum amyloid A decreased over time. The mRNA expression of the proinflammatory related genes TLR4, TNFA, IL8, and IL1B had a positive quadratic effect of time. A time effect was observed for the cell membrane sodium-dependent glucose transporter SLC5A1, for the major carbohydrate facilitated transporter SLC2A2, and water transport function AQP3, where SLC5A1 and AQP3 had a negative quadratic effect over time. Our data support the use of the fecal RNA as a noninvasive tool to investigate intestinal transcriptomic profiling of dairy calves experiencing diarrhea, which would be advantageous for future research including nutritional effects and health conditions.",2018 Jan 26,"['Rosa, Fernanda', 'Busato, Sebastiano', 'Avaroma, Fatima C.', 'Linville, Kali', 'Trevisi, Erminio', 'Osorio, Johan S.', 'Bionaz, Massimo']",PLoS One,,,False
137c77a97b865b5d85e90b50782a1bdf78539ec4,PMC,Multicenter Evaluation of the ePlex Respiratory Pathogen Panel for the Detection of Viral and Bacterial Respiratory Tract Pathogens in Nasopharyngeal Swabs,http://dx.doi.org/10.1128/JCM.01658-17,PMC5786739,29212701,CC BY,"The performance of the new ePlex Respiratory Pathogen (RP) panel (GenMark Diagnostics) for the simultaneous detection of 19 viruses (influenza A virus; influenza A H1 virus; influenza A 2009 H1 virus; influenza A H3 virus; influenza B virus; adenovirus; coronaviruses [HKU1, OC43, NL63, and 229E]; human rhinovirus/enterovirus; human metapneumovirus; parainfluenza viruses 1, 2, 3, and 4; and respiratory syncytial virus [RSV] [RSV subtype A and RSV subtype B]) and 2 bacteria (Mycoplasma pneumoniae and Chlamydia pneumoniae) was evaluated. Prospectively and retrospectively collected nasopharyngeal swab (NPS) specimens (n = 2,908) were evaluated by using the ePlex RP panel, with the bioMérieux/BioFire FilmArray Respiratory Panel (BioFire RP) as the comparator method. Discordance analysis was performed by using target-specific PCRs and bidirectional sequencing. The reproducibility of the assay was evaluated by using reproducibility panels comprised of 6 pathogens. The overall agreement between the ePlex RP and BioFire RP results was >95% for all targets. Positive percent agreement with the BioFire RP result for viruses ranged from 85.1% (95% confidence interval [CI], 80.2% to 88.9%) to 95.1% (95% CI, 89.0% to 97.9%), while negative percent agreement values ranged from 99.5% (95% CI, 99.1% to 99.7%) to 99.8% (95% CI, 99.5% to 99.9%). Additional testing of discordant targets (12%; 349/2,908) confirmed the results of ePlex RP for 38% (131/349) of samples tested. Reproducibility was 100% for all targets tested, with the exception of adenovirus, for which reproducibilities were 91.6% at low virus concentrations and 100% at moderate virus concentrations. The ePlex RP panel offers a new, rapid, and sensitive “sample-to-answer” multiplex panel for the detection of the most common viral and bacterial respiratory pathogens.",2018 Jan 24,"['Babady, N. Esther', 'England, Matthew R.', 'Jurcic Smith, Kristen L.', 'He, Taojun', 'Wijetunge, Dona Saumya', 'Tang, Yi-Wei', 'Chamberland, Robin R.', 'Menegus, Marilyn', 'Swierkosz, Ella M.', 'Jerris, Robert C.', 'Greene, Wallace']",J Clin Microbiol,,,True
77767601efaf0f884a057214886e0dc06a22f27b,PMC,Multicenter Evaluation of the ePlex Respiratory Pathogen Panel for the Detection of Viral and Bacterial Respiratory Tract Pathogens in Nasopharyngeal Swabs,http://dx.doi.org/10.1128/JCM.01658-17,PMC5786739,29212701,CC BY,"The performance of the new ePlex Respiratory Pathogen (RP) panel (GenMark Diagnostics) for the simultaneous detection of 19 viruses (influenza A virus; influenza A H1 virus; influenza A 2009 H1 virus; influenza A H3 virus; influenza B virus; adenovirus; coronaviruses [HKU1, OC43, NL63, and 229E]; human rhinovirus/enterovirus; human metapneumovirus; parainfluenza viruses 1, 2, 3, and 4; and respiratory syncytial virus [RSV] [RSV subtype A and RSV subtype B]) and 2 bacteria (Mycoplasma pneumoniae and Chlamydia pneumoniae) was evaluated. Prospectively and retrospectively collected nasopharyngeal swab (NPS) specimens (n = 2,908) were evaluated by using the ePlex RP panel, with the bioMérieux/BioFire FilmArray Respiratory Panel (BioFire RP) as the comparator method. Discordance analysis was performed by using target-specific PCRs and bidirectional sequencing. The reproducibility of the assay was evaluated by using reproducibility panels comprised of 6 pathogens. The overall agreement between the ePlex RP and BioFire RP results was >95% for all targets. Positive percent agreement with the BioFire RP result for viruses ranged from 85.1% (95% confidence interval [CI], 80.2% to 88.9%) to 95.1% (95% CI, 89.0% to 97.9%), while negative percent agreement values ranged from 99.5% (95% CI, 99.1% to 99.7%) to 99.8% (95% CI, 99.5% to 99.9%). Additional testing of discordant targets (12%; 349/2,908) confirmed the results of ePlex RP for 38% (131/349) of samples tested. Reproducibility was 100% for all targets tested, with the exception of adenovirus, for which reproducibilities were 91.6% at low virus concentrations and 100% at moderate virus concentrations. The ePlex RP panel offers a new, rapid, and sensitive “sample-to-answer” multiplex panel for the detection of the most common viral and bacterial respiratory pathogens.",2018 Jan 24,"['Babady, N. Esther', 'England, Matthew R.', 'Jurcic Smith, Kristen L.', 'He, Taojun', 'Wijetunge, Dona Saumya', 'Tang, Yi-Wei', 'Chamberland, Robin R.', 'Menegus, Marilyn', 'Swierkosz, Ella M.', 'Jerris, Robert C.', 'Greene, Wallace']",J Clin Microbiol,,,False
b54f08610e08f2cb15fa8bb649bfe09658843416,PMC,Genomic signal processing for DNA sequence clustering,http://dx.doi.org/10.7717/peerj.4264,PMC5786891,29379686,CC BY,"Genomic signal processing (GSP) methods which convert DNA data to numerical values have recently been proposed, which would offer the opportunity of employing existing digital signal processing methods for genomic data. One of the most used methods for exploring data is cluster analysis which refers to the unsupervised classification of patterns in data. In this paper, we propose a novel approach for performing cluster analysis of DNA sequences that is based on the use of GSP methods and the K-means algorithm. We also propose a visualization method that facilitates the easy inspection and analysis of the results and possible hidden behaviors. Our results support the feasibility of employing the proposed method to find and easily visualize interesting features of sets of DNA data.",2018 Jan 24,"['Mendizabal-Ruiz, Gerardo', 'Román-Godínez, Israel', 'Torres-Ramos, Sulema', 'Salido-Ruiz, Ricardo A.', 'Vélez-Pérez, Hugo', 'Morales, J. Alejandro']",PeerJ,,,True
dedf310e36616461c82de98d9b0ceae75c30e5cd,PMC,Genomic signal processing for DNA sequence clustering,http://dx.doi.org/10.7717/peerj.4264,PMC5786891,29379686,CC BY,"Genomic signal processing (GSP) methods which convert DNA data to numerical values have recently been proposed, which would offer the opportunity of employing existing digital signal processing methods for genomic data. One of the most used methods for exploring data is cluster analysis which refers to the unsupervised classification of patterns in data. In this paper, we propose a novel approach for performing cluster analysis of DNA sequences that is based on the use of GSP methods and the K-means algorithm. We also propose a visualization method that facilitates the easy inspection and analysis of the results and possible hidden behaviors. Our results support the feasibility of employing the proposed method to find and easily visualize interesting features of sets of DNA data.",2018 Jan 24,"['Mendizabal-Ruiz, Gerardo', 'Román-Godínez, Israel', 'Torres-Ramos, Sulema', 'Salido-Ruiz, Ricardo A.', 'Vélez-Pérez, Hugo', 'Morales, J. Alejandro']",PeerJ,,,True
289edbe9e28f26ea1d2de597c085e0f6e3009aed,PMC,Case report: a fatal case of disseminated adenovirus infection in a non-transplant adult haematology patient,http://dx.doi.org/10.1186/s12879-018-2962-7,PMC5787257,29374466,CC BY,"BACKGROUND: We report a fatal case of disseminated adenovirus infection in a non-transplant haematology adult patient with chronic lymphocytic leukaemia who had completed combination chemoimmunotherapy a few months before developing respiratory symptoms. In such non-transplant patients, monitoring for adenovirus in the blood is not routine. However, with adenoviruses, when there is a more peripheral (i.e. non-blood) site of infection such as the chest, serial adenovirus monitoring in blood for the duration of that illness may be warranted. CASE PRESENTATION: This case started with an initial bacterial chest infection that responded to treatment, followed by an adenovirus pneumonitis that disseminated to his blood a week later with levels of up to 92 million adenovirus DNA copies/ml. Despite prompt treatment with cidofovir, his respiratory function continued to deteriorate over the next two weeks and he was moved to intensive care. Intravenous immunoglobulin and ribavirin were subsequently added to his treatment. However, he died soon after this with a final adenovirus load of 20 million copies/ml in his blood. CONCLUSIONS: We recommend that even in non-transplant haematology patients, where such patients present with an acute respiratory adenovirus infection, teams should consider checking the blood for adenovirus to check for signs of disseminated infection. The earlier this can be tested, the earlier treatment can be initiated (if adenovirus positive), which may produce more successful clinical outcomes.",2018 Jan 27,"['Joffe, Michael', 'Wagner, Simon D.', 'Tang, Julian W.']",BMC Infect Dis,,,True
4c9604ca5c3d30db29127225cc52ad90b50c1b13,PMC,Epidemiology characteristics of human coronaviruses in patients with respiratory infection symptoms and phylogenetic analysis of HCoV-OC43 during 2010-2015 in Guangzhou,http://dx.doi.org/10.1371/journal.pone.0191789,PMC5788356,29377913,CC BY,"Human coronavirus (HCoV) is one of the most common causes of respiratory tract infection throughout the world. To investigate the epidemiological and genetic variation of HCoV in Guangzhou, south China, we collected totally 13048 throat and nasal swab specimens from adults and children with fever and acute upper respiratory infection symptoms in Gunazhou, south China between July 2010 and June 2015, and the epidemiological features of HCoV and its species were studied. Specimens were screened for HCoV by real-time RT-PCR, and 7 other common respiratory viruses were tested simultaneously by PCR or real-time PCR. HCoV was detected in 294 cases (2.25%) of the 13048 samples, with most of them inpatients (251 cases, 85.4% of HCoV positive cases) and young children not in nursery (53.06%, 156 out of 294 HCoV positive cases). Four HCoVs, as OC43, 229E, NL63 and HKU1 were detected prevalent during 2010–2015 in Guangzhou, and among the HCoV positive cases, 60.20% were OC43, 16.67% were 229E, 14.97% were NL63 and 7.82% were HKU1. The month distribution showed that totally HCoV was prevalent in winter, but differences existed in different species. The 5 year distribution of HCoV showed a peak-valley distribution trend, with the detection rate higher in 2011 and 2013 whereas lower in 2010, 2012 and 2014. The age distribution revealed that children (especially those <3 years old) and old people (>50 years) were both high risk groups to be infected by HCoV. Of the 294 HCoV positive patients, 34.69% (101 cases) were co-infected by other common respiratory viruses, and influenza virus was the most common co-infecting virus (30/101, 29.70%). Fifteen HCoV-OC43 positive samples of 2013–2014 were selected for S gene sequencing and phylogenetic analysis, and the results showed that the 15 strains could be divided into 2 clusters in the phylogenetic tree, 12 strains of which formed a separate cluster that was closer to genotype G found in Malaysia. It was revealed for the first time that genotype B and genotype G of HCoV-OC43 co-circulated and the newly defined genotype G was epidemic as a dominant genotype during 2013–2014 in Guanzhou, south China.",2018 Jan 29,"['Zhang, Su-fen', 'Tuo, Jiu-ling', 'Huang, Xu-bin', 'Zhu, Xun', 'Zhang, Ding-mei', 'Zhou, Kai', 'Yuan, Lei', 'Luo, Hong-jiao', 'Zheng, Bo-jian', 'Yuen, Kwok-yung', 'Li, Meng-feng', 'Cao, Kai-yuan', 'Xu, Lin']",PLoS One,,,True
e495a03cd94f48b0ad88347e1b5c0680fab819b4,PMC,"New Antimicrobial Potential and Structural Properties of PAFB: A Cationic, Cysteine-Rich Protein from Penicillium chrysogenum Q176",http://dx.doi.org/10.1038/s41598-018-20002-2,PMC5788923,29379111,CC BY,"Small, cysteine-rich and cationic proteins with antimicrobial activity are produced by diverse organisms of all kingdoms and represent promising molecules for drug development. The ancestor of all industrial penicillin producing strains, the ascomycete Penicillium chryosgenum Q176, secretes the extensively studied antifungal protein PAF. However, the genome of this strain harbours at least two more genes that code for other small, cysteine-rich and cationic proteins with potential antifungal activity. In this study, we characterized the pafB gene product that shows high similarity to PgAFP from P. chrysogenum R42C. Although abundant and timely regulated pafB gene transcripts were detected, we could not identify PAFB in the culture broth of P. chrysogenum Q176. Therefore, we applied a P. chrysogenum-based expression system to produce sufficient amounts of recombinant PAFB to address unanswered questions concerning the structure and antimicrobial function. Nuclear magnetic resonance (NMR)-based analyses revealed a compact β-folded structure, comprising five β-strands connected by four solvent exposed and flexible loops and an “abcabc” disulphide bond pattern. We identified PAFB as an inhibitor of growth of human pathogenic moulds and yeasts. Furthermore, we document for the first time an anti-viral activity for two members of the small, cysteine-rich and cationic protein group from ascomycetes.",2018 Jan 29,"['Huber, Anna', 'Hajdu, Dorottya', 'Bratschun-Khan, Doris', 'Gáspári, Zoltán', 'Varbanov, Mihayl', 'Philippot, Stéphanie', 'Fizil, Ádám', 'Czajlik, András', 'Kele, Zoltán', 'Sonderegger, Christoph', 'Galgóczy, László', 'Bodor, Andrea', 'Marx, Florentine', 'Batta, Gyula']",Sci Rep,,,True
68405384d530f6beb4fd8cce0841878a72640d28,PMC,"New Antimicrobial Potential and Structural Properties of PAFB: A Cationic, Cysteine-Rich Protein from Penicillium chrysogenum Q176",http://dx.doi.org/10.1038/s41598-018-20002-2,PMC5788923,29379111,CC BY,"Small, cysteine-rich and cationic proteins with antimicrobial activity are produced by diverse organisms of all kingdoms and represent promising molecules for drug development. The ancestor of all industrial penicillin producing strains, the ascomycete Penicillium chryosgenum Q176, secretes the extensively studied antifungal protein PAF. However, the genome of this strain harbours at least two more genes that code for other small, cysteine-rich and cationic proteins with potential antifungal activity. In this study, we characterized the pafB gene product that shows high similarity to PgAFP from P. chrysogenum R42C. Although abundant and timely regulated pafB gene transcripts were detected, we could not identify PAFB in the culture broth of P. chrysogenum Q176. Therefore, we applied a P. chrysogenum-based expression system to produce sufficient amounts of recombinant PAFB to address unanswered questions concerning the structure and antimicrobial function. Nuclear magnetic resonance (NMR)-based analyses revealed a compact β-folded structure, comprising five β-strands connected by four solvent exposed and flexible loops and an “abcabc” disulphide bond pattern. We identified PAFB as an inhibitor of growth of human pathogenic moulds and yeasts. Furthermore, we document for the first time an anti-viral activity for two members of the small, cysteine-rich and cationic protein group from ascomycetes.",2018 Jan 29,"['Huber, Anna', 'Hajdu, Dorottya', 'Bratschun-Khan, Doris', 'Gáspári, Zoltán', 'Varbanov, Mihayl', 'Philippot, Stéphanie', 'Fizil, Ádám', 'Czajlik, András', 'Kele, Zoltán', 'Sonderegger, Christoph', 'Galgóczy, László', 'Bodor, Andrea', 'Marx, Florentine', 'Batta, Gyula']",Sci Rep,,,True
48c0614e47f4de8d1d1f1edbf9c9663cd014926d,PMC,"Global ubiquitination analysis reveals extensive modification and proteasomal degradation of cowpox virus proteins, but preservation of viral cores",http://dx.doi.org/10.1038/s41598-018-20130-9,PMC5788924,29379051,CC BY,"The emergence of Variola virus-like viruses by natural evolution of zoonotic Orthopoxviruses, like Cowpox virus (CPXV), is a global health threat. The proteasome is essential for poxvirus replication, making the viral components interacting with the ubiquitin-proteasome system attractive antiviral targets. We show that proteasome inhibition impairs CPXV replication by prevention of uncoating, suggesting that uncoating is mediated by proteasomal degradation of viral core proteins. Although Orthopoxvirus particles contain considerable amounts of ubiquitin, distinct modification sites are largely unknown. Therefore, for the first time, we analyzed globally ubiquitination sites in CPXV mature virion proteins using LC-MS/MS. Identification of 137 conserved sites in 54 viral proteins among five CPXV strains revealed extensive ubiquitination of structural core proteins. Moreover, since virions contained primarily K48-linked polyubiquitin, we hypothesized that core proteins are modified accordingly. However, quantitative analysis of ubiquitinated CPXV proteins early in infection showed no proteasomal degradation of core proteins. Instead, our data indicate that the recently suggested proteasomal regulation of the uncoating factor E5 is a prerequisite for uncoating. Expanding our understanding of poxvirus uncoating and elucidating a multitude of novel ubiquitination sites in poxvirus proteins, the present study verifies the major biological significance of ubiquitin in poxvirus infection.",2018 Jan 29,"['Grossegesse, Marica', 'Doellinger, Joerg', 'Fritsch, Annemarie', 'Laue, Michael', 'Piesker, Janett', 'Schaade, Lars', 'Nitsche, Andreas']",Sci Rep,,,True
703744c49c4908516297844dee0ba03affc36a74,PMC,"Global ubiquitination analysis reveals extensive modification and proteasomal degradation of cowpox virus proteins, but preservation of viral cores",http://dx.doi.org/10.1038/s41598-018-20130-9,PMC5788924,29379051,CC BY,"The emergence of Variola virus-like viruses by natural evolution of zoonotic Orthopoxviruses, like Cowpox virus (CPXV), is a global health threat. The proteasome is essential for poxvirus replication, making the viral components interacting with the ubiquitin-proteasome system attractive antiviral targets. We show that proteasome inhibition impairs CPXV replication by prevention of uncoating, suggesting that uncoating is mediated by proteasomal degradation of viral core proteins. Although Orthopoxvirus particles contain considerable amounts of ubiquitin, distinct modification sites are largely unknown. Therefore, for the first time, we analyzed globally ubiquitination sites in CPXV mature virion proteins using LC-MS/MS. Identification of 137 conserved sites in 54 viral proteins among five CPXV strains revealed extensive ubiquitination of structural core proteins. Moreover, since virions contained primarily K48-linked polyubiquitin, we hypothesized that core proteins are modified accordingly. However, quantitative analysis of ubiquitinated CPXV proteins early in infection showed no proteasomal degradation of core proteins. Instead, our data indicate that the recently suggested proteasomal regulation of the uncoating factor E5 is a prerequisite for uncoating. Expanding our understanding of poxvirus uncoating and elucidating a multitude of novel ubiquitination sites in poxvirus proteins, the present study verifies the major biological significance of ubiquitin in poxvirus infection.",2018 Jan 29,"['Grossegesse, Marica', 'Doellinger, Joerg', 'Fritsch, Annemarie', 'Laue, Michael', 'Piesker, Janett', 'Schaade, Lars', 'Nitsche, Andreas']",Sci Rep,,,True
aac8b9ab0f36b70cdaf2e6c239d581d4b3737aed,PMC,A Low-Cost Palmtop High-Speed Capillary Electrophoresis Bioanalyzer with Laser Induced Fluorescence Detection,http://dx.doi.org/10.1038/s41598-018-20058-0,PMC5789010,29379053,CC BY,"In this work, we developed a miniaturized palmtop high-speed capillary electrophoresis (CE) system integrating whole modules, including picoliter-scale sample injection, short capillary-based fast CE, high-voltage power supply, orthogonal laser induced fluorescence (LIF) detection, battery, system control, on-line data acquisition, processing, storage, and display modules. A strategy of minimalist miniaturization combining minimal system design and low-cost system construction was adopted to achieve the instrument miniaturization with extremely low cost, which is differing from the current microfabrication strategy used in most reported miniaturized CE systems. With such a strategy, the total size of the bioanalyzer was minimized to 90 × 75 × 77 mm (length × width × height) and the instrument cost was reduced to ca. $500, which demonstrated the smallest and lowest-cost CE instrument with LIF detection in so far reported systems. The present bioanalyzer also exhibited comparable analytical performances to previously-reported high-speed CE systems. A limit of detection of 1.02 nM sodium fluorescein was obtained. Fast separations were achieved for multiple types of samples as amino acids, amino acid enantiomers, DNA fragments, and proteins with high efficiency. We applied this instrument in colorectal cancer diagnosis for detecting KRAS mutation status by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.",2018 Jan 29,"['Pan, Jian-Zhang', 'Fang, Pan', 'Fang, Xiao-Xia', 'Hu, Ting-Ting', 'Fang, Jin', 'Fang, Qun']",Sci Rep,,,True
8b7d76ba81c3eb5ddf6e9330e16ce1189fe1f08b,PMC,Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model,http://dx.doi.org/10.1186/s13287-018-0774-8,PMC5789598,29378639,CC BY,"BACKGROUND: Mesenchymal stem (stromal) cells (MSCs) mediate their immunoregulatory and tissue repair functions by secreting paracrine factors, including extracellular vesicles (EVs). In several animal models of human diseases, MSC-EVs mimic the beneficial effects of MSCs. Influenza viruses cause annual outbreaks of acute respiratory illness resulting in significant mortality and morbidity. Influenza viruses constantly evolve, thus generating drug-resistant strains and rendering current vaccines less effective against the newly generated strains. Therefore, new therapies that can control virus replication and the inflammatory response of the host are needed. The objective of this study was to examine if MSC-EV treatment can attenuate influenza virus-induced acute lung injury in a preclinical model. METHODS: We isolated EVs from swine bone marrow-derived MSCs. Morphology of MSC-EVs was determined by electron microscopy and expression of mesenchymal markers was examined by flow cytometry. Next, we examined the anti-influenza activity of MSC-EVs in vitro in lung epithelial cells and anti-viral and immunomodulatory properties in vivo in a pig model of influenza virus. RESULTS: MSC-EVs were isolated from MSC-conditioned medium by ultracentrifugation. MSC-EVs were round-shaped and, similarly to MSCs, expressed mesenchymal markers and lacked the expression of swine leukocyte antigens I and II. Incubation of PKH-26-labeled EVs with lung epithelial cells revealed that MSC-EVs incorporated into the epithelial cells. Next, we examined the anti-influenza and anti-inflammatory properties of MSC-EVs. MSC-EVs inhibited the hemagglutination activity of avian, swine, and human influenza viruses at concentrations of 1.25–5 μg/ml. MSC-EVs inhibited influenza virus replication and virus-induced apoptosis in lung epithelial cells. The anti-influenza activity of MSC-EVs was due to transfer of RNAs from EVs to epithelial cells since pre-incubation of MSC-EVs with RNase enzyme abrogated the anti-influenza activity of MSC-EVs. In a pig model of influenza virus, intratracheal administration of MSC-EVs 12 h after influenza virus infection significantly reduced virus shedding in the nasal swabs, influenza virus replication in the lungs, and virus-induced production of proinflammatory cytokines in the lungs of influenza-infected pigs. The histopathological findings revealed that MSC-EVs alleviated influenza virus-induced lung lesions in pigs. CONCLUSIONS: Our data demonstrated in a relevant preclinical large animal model of influenza virus that MSC-EVs possessed anti-influenza and anti-inflammatory properties and that EVs may be used as cell-free therapy for influenza in humans.",2018 Jan 29,"['Khatri, Mahesh', 'Richardson, Levi Arthur', 'Meulia, Tea']",Stem Cell Res Ther,,,True
fa0a24c1abcfc2964ea0a8f4c4c3df322713eca7,PMC,"Traditional uses of medicinal plants used by Indigenous communities for veterinary practices at Bajaur Agency, Pakistan",http://dx.doi.org/10.1186/s13002-018-0212-0,PMC5789696,29378636,CC BY,"BACKGROUND: The pastoral lifestyle of Indigenous communities of Bajaur Agency is bringing them close to natural remedies for treating their domestic animals. Several studies have been conducted across the globe describing the importance of traditional knowledge in veterinary care. Therefore, this study was planned with the aim to record knowledge on ethnoveterinary practices from the remote areas and share sit with other communities through published literature. METHODS: Data was gathered from community members through semi-structured interviews and analyzed through informant consensus factor (Fic) to evaluate the consent of current ethnoveterinary practices among the local people. RESULTS: In total, 73 medicinal plants were recorded under the ethnoveterinary practices. Most widely used medicinal plants with maximum use reports (URs) were Visnaga daucoides Gaertn., Foeniculum vulgare Mill., Solanum virginianum L., Withania somnifera (L.) Dunal, Glycyrrhiza glabra L., and Curcuma longa L. New medicinal values were found with confidential level of citations for species including Heracleum candicans and Glycerhiza glabra. Family Apiaceae was the utmost family with high number (7 species) of medicinal plants. Maximum number of medicinal plants (32) was used for gastric problems. High Fic was recorded for dermatological (0.97) followed by reproductive (0.93) and gastrointestinal disorders (0.92). The main route of remedies administration was oral. CONCLUSIONS: Current study revealed that the study area has sufficient knowledge on ethnoveterinary medicinal plants. This knowledge is in the custody of nomadic grazers, herders, and aged community members. Plants with new medicinal uses need to be validated phytochemically and pharmacologically for the development of new alternative drugs for veterinary purposes.",2018 Jan 29,"['Aziz, Muhammad Abdul', 'Khan, Amir Hasan', 'Adnan, Muhammad', 'Ullah, Habib']",J Ethnobiol Ethnomed,,,True
99c90b4bde62f92bba4c0e244b358521c5209801,PMC,Bismuth antimicrobial drugs serve as broad-spectrum metallo-β-lactamase inhibitors,http://dx.doi.org/10.1038/s41467-018-02828-6,PMC5789847,29382822,CC BY,"Drug-resistant superbugs pose a huge threat to human health. Infections by Enterobacteriaceae producing metallo-β-lactamases (MBLs), e.g., New Delhi metallo-β-lactamase 1 (NDM-1) are very difficult to treat. Development of effective MBL inhibitors to revive the efficacy of existing antibiotics is highly desirable. However, such inhibitors are not clinically available till now. Here we show that an anti-Helicobacter pylori drug, colloidal bismuth subcitrate (CBS), and related Bi(III) compounds irreversibly inhibit different types of MBLs via the mechanism, with one Bi(III) displacing two Zn(II) ions as revealed by X-ray crystallography, leading to the release of Zn(II) cofactors. CBS restores meropenem (MER) efficacy against MBL-positive bacteria in vitro, and in mice infection model, importantly, also slows down the development of higher-level resistance in NDM-1-positive bacteria. This study demonstrates a high potential of Bi(III) compounds as the first broad-spectrum B1 MBL inhibitors to treat MBL-positive bacterial infection in conjunction with existing carbapenems.",2018 Jan 30,"['Wang, Runming', 'Lai, Tsz-Pui', 'Gao, Peng', 'Zhang, Hongmin', 'Ho, Pak-Leung', 'Woo, Patrick Chiu-Yat', 'Ma, Guixing', 'Kao, Richard Yi-Tsun', 'Li, Hongyan', 'Sun, Hongzhe']",Nat Commun,,,False
5768cbcc822fdcab18dacf976c31062c549733c9,PMC,Bismuth antimicrobial drugs serve as broad-spectrum metallo-β-lactamase inhibitors,http://dx.doi.org/10.1038/s41467-018-02828-6,PMC5789847,29382822,CC BY,"Drug-resistant superbugs pose a huge threat to human health. Infections by Enterobacteriaceae producing metallo-β-lactamases (MBLs), e.g., New Delhi metallo-β-lactamase 1 (NDM-1) are very difficult to treat. Development of effective MBL inhibitors to revive the efficacy of existing antibiotics is highly desirable. However, such inhibitors are not clinically available till now. Here we show that an anti-Helicobacter pylori drug, colloidal bismuth subcitrate (CBS), and related Bi(III) compounds irreversibly inhibit different types of MBLs via the mechanism, with one Bi(III) displacing two Zn(II) ions as revealed by X-ray crystallography, leading to the release of Zn(II) cofactors. CBS restores meropenem (MER) efficacy against MBL-positive bacteria in vitro, and in mice infection model, importantly, also slows down the development of higher-level resistance in NDM-1-positive bacteria. This study demonstrates a high potential of Bi(III) compounds as the first broad-spectrum B1 MBL inhibitors to treat MBL-positive bacterial infection in conjunction with existing carbapenems.",2018 Jan 30,"['Wang, Runming', 'Lai, Tsz-Pui', 'Gao, Peng', 'Zhang, Hongmin', 'Ho, Pak-Leung', 'Woo, Patrick Chiu-Yat', 'Ma, Guixing', 'Kao, Richard Yi-Tsun', 'Li, Hongyan', 'Sun, Hongzhe']",Nat Commun,,,False
49e1868b232e6ec98ae7cbc0745613925205e056,PMC,Bismuth antimicrobial drugs serve as broad-spectrum metallo-β-lactamase inhibitors,http://dx.doi.org/10.1038/s41467-018-02828-6,PMC5789847,29382822,CC BY,"Drug-resistant superbugs pose a huge threat to human health. Infections by Enterobacteriaceae producing metallo-β-lactamases (MBLs), e.g., New Delhi metallo-β-lactamase 1 (NDM-1) are very difficult to treat. Development of effective MBL inhibitors to revive the efficacy of existing antibiotics is highly desirable. However, such inhibitors are not clinically available till now. Here we show that an anti-Helicobacter pylori drug, colloidal bismuth subcitrate (CBS), and related Bi(III) compounds irreversibly inhibit different types of MBLs via the mechanism, with one Bi(III) displacing two Zn(II) ions as revealed by X-ray crystallography, leading to the release of Zn(II) cofactors. CBS restores meropenem (MER) efficacy against MBL-positive bacteria in vitro, and in mice infection model, importantly, also slows down the development of higher-level resistance in NDM-1-positive bacteria. This study demonstrates a high potential of Bi(III) compounds as the first broad-spectrum B1 MBL inhibitors to treat MBL-positive bacterial infection in conjunction with existing carbapenems.",2018 Jan 30,"['Wang, Runming', 'Lai, Tsz-Pui', 'Gao, Peng', 'Zhang, Hongmin', 'Ho, Pak-Leung', 'Woo, Patrick Chiu-Yat', 'Ma, Guixing', 'Kao, Richard Yi-Tsun', 'Li, Hongyan', 'Sun, Hongzhe']",Nat Commun,,,True
edebddfa84cd285915ccd9c8b4f428bda6676f89,PMC,Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity,http://dx.doi.org/10.1038/s41598-018-20305-4,PMC5789897,29382880,CC BY,"The arthropod-transmitted chikungunya virus (CHIKV) causes a flu-like disease that is characterized by incapacitating arthralgia. The re-emergence of CHIKV and the continual risk of new epidemics have reignited research in CHIKV pathogenesis. Virus-specific antibodies have been shown to control virus clearance, but antibodies present at sub-neutralizing concentrations can also augment virus infection that exacerbates disease severity. To explore this occurrence, CHIKV infection was investigated in the presence of CHIKV-specific antibodies in both primary human cells and a murine macrophage cell line, RAW264.7. Enhanced attachment of CHIKV to the primary human monocytes and B cells was observed while increased viral replication was detected in RAW264.7 cells. Blocking of specific Fc receptors (FcγRs) led to the abrogation of these observations. Furthermore, experimental infection in adult mice showed that animals had higher viral RNA loads and endured more severe joint inflammation in the presence of sub-neutralizing concentrations of CHIKV-specific antibodies. In addition, CHIKV infection in 11 days old mice under enhancing condition resulted in higher muscles viral RNA load detected and death. These observations provide the first evidence of antibody-mediated enhancement in CHIKV infection and pathogenesis and could also be relevant for other important arboviruses such as Zika virus.",2018 Jan 30,"['Lum, Fok-Moon', 'Couderc, Thérèse', 'Chia, Bing-Shao', 'Ong, Ruo-Yan', 'Her, Zhisheng', 'Chow, Angela', 'Leo, Yee-Sin', 'Kam, Yiu-Wing', 'Rénia, Laurent', 'Lecuit, Marc', 'Ng, Lisa F. P.']",Sci Rep,,,False
bda897976d2a119dd7f4505065d769c3b93cddf7,PMC,Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity,http://dx.doi.org/10.1038/s41598-018-20305-4,PMC5789897,29382880,CC BY,"The arthropod-transmitted chikungunya virus (CHIKV) causes a flu-like disease that is characterized by incapacitating arthralgia. The re-emergence of CHIKV and the continual risk of new epidemics have reignited research in CHIKV pathogenesis. Virus-specific antibodies have been shown to control virus clearance, but antibodies present at sub-neutralizing concentrations can also augment virus infection that exacerbates disease severity. To explore this occurrence, CHIKV infection was investigated in the presence of CHIKV-specific antibodies in both primary human cells and a murine macrophage cell line, RAW264.7. Enhanced attachment of CHIKV to the primary human monocytes and B cells was observed while increased viral replication was detected in RAW264.7 cells. Blocking of specific Fc receptors (FcγRs) led to the abrogation of these observations. Furthermore, experimental infection in adult mice showed that animals had higher viral RNA loads and endured more severe joint inflammation in the presence of sub-neutralizing concentrations of CHIKV-specific antibodies. In addition, CHIKV infection in 11 days old mice under enhancing condition resulted in higher muscles viral RNA load detected and death. These observations provide the first evidence of antibody-mediated enhancement in CHIKV infection and pathogenesis and could also be relevant for other important arboviruses such as Zika virus.",2018 Jan 30,"['Lum, Fok-Moon', 'Couderc, Thérèse', 'Chia, Bing-Shao', 'Ong, Ruo-Yan', 'Her, Zhisheng', 'Chow, Angela', 'Leo, Yee-Sin', 'Kam, Yiu-Wing', 'Rénia, Laurent', 'Lecuit, Marc', 'Ng, Lisa F. P.']",Sci Rep,,,True
d521a22ac03c5c56e1ca2aea0e90f322b348851b,PMC,Characterization of Influenza Virus Pseudotyped with Ebolavirus Glycoprotein,http://dx.doi.org/10.1128/JVI.00941-17,PMC5790926,29212933,CC BY,"We have produced a new Ebola virus pseudotype, E-S-FLU, that can be handled in biosafety level 1/2 containment for laboratory analysis. The E-S-FLU virus is a single-cycle influenza virus coated with Ebolavirus glycoprotein, and it encodes enhanced green fluorescence protein as a reporter that replaces the influenza virus hemagglutinin. MDCK-SIAT1 cells were transduced to express Ebolavirus glycoprotein as a stable transmembrane protein for E-S-FLU virus production. Infection of cells with the E-S-FLU virus was dependent on the Niemann-Pick C1 protein, which is the well-characterized receptor for Ebola virus entry at the late endosome/lysosome membrane. The E-S-FLU virus was neutralized specifically by an anti-Ebolavirus glycoprotein antibody and a variety of small drug molecules that are known to inhibit the entry of wild-type Ebola virus. To demonstrate the application of this new Ebola virus pseudotype, we show that a single laboratory batch was sufficient to screen a library (LOPAC(1280); Sigma) of 1,280 pharmacologically active compounds for inhibition of virus entry. A total of 215 compounds inhibited E-S-FLU virus infection, while only 22 inhibited the control H5-S-FLU virus coated in H5 hemagglutinin. These inhibitory compounds have very dispersed targets and mechanisms of action, e.g., calcium channel blockers, estrogen receptor antagonists, antihistamines, serotonin uptake inhibitors, etc., and this correlates with inhibitor screening results obtained with other pseudotypes or wild-type Ebola virus in the literature. The E-S-FLU virus is a new tool for Ebola virus cell entry studies and is easily applied to high-throughput screening assays for small-molecule inhibitors or antibodies. IMPORTANCE Ebola virus is in the Filoviridae family and is a biosafety level 4 pathogen. There are no FDA-approved therapeutics for Ebola virus. These characteristics warrant the development of surrogates for Ebola virus that can be handled in more convenient laboratory containment to study the biology of the virus and screen for inhibitors. Here we characterized a new surrogate, named E-S-FLU virus, that is based on a disabled influenza virus core coated with the Ebola virus surface protein but does not contain any genetic information from the Ebola virus itself. We show that E-S-FLU virus uses the same cell entry pathway as wild-type Ebola virus. As an example of the ease of use of E-S-FLU virus in biosafety level 1/2 containment, we showed that a single production batch could provide enough surrogate virus to screen a standard small-molecule library of 1,280 candidates for inhibitors of viral entry.",2018 Jan 30,"['Xiao, Julie Huiyuan', 'Rijal, Pramila', 'Schimanski, Lisa', 'Tharkeshwar, Arun Kumar', 'Wright, Edward', 'Annaert, Wim', 'Townsend, Alain']",J Virol,,,True
01c6ed4b3dee404e4d908af40ab93183b573e9ec,PMC,Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial,http://dx.doi.org/10.1186/s13063-017-2427-0,PMC5791210,29382391,CC BY,"BACKGROUND: It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. DISCUSSION: This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02845843. Registered on 27 July 2016. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-017-2427-0) contains supplementary material, which is available to authorized users.",2018 Jan 30,"['Arabi, Yaseen M.', 'Alothman, Adel', 'Balkhy, Hanan H.', 'Al-Dawood, Abdulaziz', 'AlJohani, Sameera', 'Al Harbi, Shmeylan', 'Kojan, Suleiman', 'Al Jeraisy, Majed', 'Deeb, Ahmad M.', 'Assiri, Abdullah M.', 'Al-Hameed, Fahad', 'AlSaedi, Asim', 'Mandourah, Yasser', 'Almekhlafi, Ghaleb A.', 'Sherbeeni, Nisreen Murad', 'Elzein, Fatehi Elnour', 'Memon, Javed', 'Taha, Yusri', 'Almotairi, Abdullah', 'Maghrabi, Khalid A.', 'Qushmaq, Ismael', 'Al Bshabshe, Ali', 'Kharaba, Ayman', 'Shalhoub, Sarah', 'Jose, Jesna', 'Fowler, Robert A.', 'Hayden, Frederick G.', 'Hussein, Mohamed A.', None]",Trials,,,True
5c0beb565af7a9bcad425207e8b5141540ff3778,PMC,Estimates of global research productivity in using nicotine replacement therapy for tobacco cessation: a bibliometric study,http://dx.doi.org/10.1186/s12992-018-0335-z,PMC5791372,29382348,CC BY,"BACKGROUND: Tobacco use is a major healthcare problem worldwide. Tobacco smoking remains the most important risk factor for both cancer and heart diseases. This study was initiated due to the lack of published data concerning the real progress in research output in the use of nicotine replacement therapy (NRT) for tobacco cessation. This study was aimed to use bibliometric analysis to estimate the NRT literature indexed in Scopus database at global level. METHODS: Core of the search strategy was the documents that contained specific words or phrases regarding NRT as keywords in the title. Publication output of most prolific countries was adjusted to the gross domestic product and population size. All citations analysis were accomplished on December 22, 2017. RESULTS: A total of 2138 references were retrieved and published from 56 countries, which were published between 1970 and 2016. The USA has the most number of published articles accounted to 986, followed by the UK (312 publications) and then Australia (102 publications), and Sweden (102 publications). No data related to NRT were published from 156 countries. No significant correlation was found between the country population size or 2016 gross domestic product values and the number of publications of the top-10 most prolific countries in the field of NRT (r = − 0.156, P = 0.664; and r = − 0.173, P = 0.632, respectively). Furthermore, there is no correlation between prevalence of tobacco smoking and number of publications of the top-10 most prolific countries in the field of NRT (r = − 0.235, P = 0.514). CONCLUSIONS: The present data reveal a solid mass of research activity on NRT. The USA was by far the predominant country in the amount of NRT-based research activity. NRT-based research activities were low or not available in most countries. The results of this study delineate a framework for better understanding the situations of current NRT research and prospective directions of the research in this field which could be applied for managing and prioritizing future research efforts in NRT research.",2018 Jan 30,"Zyoud, Sa’ed H.",Global Health,,,True
55123f88b470c8d819d169865c7fada386ee7821,PMC,Lessons learnt from implementation of the International Health Regulations: a systematic review,http://dx.doi.org/10.2471/BLT.16.189100,PMC5791773,29403114,CC BY,"OBJECTIVE: To respond to the World Health Assembly call for dissemination of lessons learnt from countries that have begun implementing the International Health Regulations, 2005 revision; IHR (2005). METHODS: In November 2015, we conducted a systematic search of the following online databases and sources: PubMed®, Embase®, Global Health, Scopus, World Health Organization (WHO) Global Index Medicus, WHO Bulletin on IHR Implementation and the International Society for Disease Surveillance. We included identified studies and reports summarizing national experience in implementing any of the IHR (2005) core capacities or their components. We excluded studies that were theoretical or referred to IHR (1969). Qualitative systematic review methodology, including meta-ethnography, was used for qualitative synthesis. FINDINGS: We analysed 51 articles from 77 countries representing all WHO Regions. The meta-syntheses identified a total of 44 lessons learnt across the eight core capacities of IHR (2005). Major themes included the need to mobilize and sustain political commitment; to adapt global requirements based on local sociocultural, epidemiological, health system and economic contexts; and to conduct baseline and follow-up assessments to monitor the status of IHR (2005) implementation. CONCLUSION: Although experiences of IHR (2005) implementation covered a wide global range, more documentation from Africa and Eastern Europe is needed. We did not find specific areas of weakness in monitoring IHR (2005); sustained monitoring of all core capacities is required to ensure effective systems. These lessons learnt could be adapted by countries in the process of meeting IHR (2005) requirements.",2018 Feb 1,"['Suthar, Amitabh B', 'Allen, Lisa G', 'Cifuentes, Sara', 'Dye, Christopher', 'Nagata, Jason M']",Bull World Health Organ,,,True
07ddf570a1c38269ac3d1826cd8d013faeb6a339,PMC,Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection,http://dx.doi.org/10.2471/BLT.17.194514,PMC5791775,29403115,CC BY,"The formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use. After the 2009–2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance. This prompted improvements in the sensitivity and specificity of the case definition for influenza – i.e. a respiratory disease that lacks uniquely defining symptomology. The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability. To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden.",2018 Feb 1,"['Fitzner, Julia', 'Qasmieh, Saba', 'Mounts, Anthony Wayne', 'Alexander, Burmaa', 'Besselaar, Terry', 'Briand, Sylvie', 'Brown, Caroline', 'Clark, Seth', 'Dueger, Erica', 'Gross, Diane', 'Hauge, Siri', 'Hirve, Siddhivinayak', 'Jorgensen, Pernille', 'Katz, Mark A', 'Mafi, Ali', 'Malik, Mamunur', 'McCarron, Margaret', 'Meerhoff, Tamara', 'Mori, Yuichiro', 'Mott, Joshua', 'Olivera, Maria Teresa da Costa', 'Ortiz, Justin R', 'Palekar, Rakhee', 'Rebelo-de-Andrade, Helena', 'Soetens, Loes', 'Yahaya, Ali Ahmed', 'Zhang, Wenqing', 'Vandemaele, Katelijn']",Bull World Health Organ,,,True
35a1fc9f21b1fd513fd01f015e091a023d50dd7e,PMC,A framework for stimulating economic investments to prevent emerging diseases,http://dx.doi.org/10.2471/BLT.17.199547,PMC5791777,29403118,CC BY,,2018 Feb 1,"['Schar, Daniel L', 'Yamey, Gavin Mark', 'Machalaba, Catherine C', 'Karesh, William B']",Bull World Health Organ,,,True
e596bfbd1ba590f07fd2514040538bb5fb9ed166,PMC,Pandemic risk: how large are the expected losses?,http://dx.doi.org/10.2471/BLT.17.199588,PMC5791779,29403116,CC BY,"There is an unmet need for greater investment in preparedness against major epidemics and pandemics. The arguments in favour of such investment have been largely based on estimates of the losses in national incomes that might occur as the result of a major epidemic or pandemic. Recently, we extended the estimate to include the valuation of the lives lost as a result of pandemic-related increases in mortality. This produced markedly higher estimates of the full value of loss that might occur as the result of a future pandemic. We parametrized an exceedance probability function for a global influenza pandemic and estimated that the expected number of influenza-pandemic-related deaths is about 720 000 per year. We calculated that the expected annual losses from pandemic risk to be about 500 billion United States dollars – or 0.6% of global income – per year. This estimate falls within – but towards the lower end of – the Intergovernmental Panel on Climate Change’s estimates of the value of the losses from global warming, which range from 0.2% to 2% of global income. The estimated percentage of annual national income represented by the expected value of losses varied by country income grouping: from a little over 0.3% in high-income countries to 1.6% in lower-middle-income countries. Most of the losses from influenza pandemics come from rare, severe events.",2018 Feb 1,"['Fan, Victoria Y', 'Jamison, Dean T', 'Summers, Lawrence H']",Bull World Health Organ,,,True
8f6e5334a3d3d325a09fa1b7e824830fb021569d,PMC,Marion Koopmans: greater regional capacity to fight disease outbreaks,http://dx.doi.org/10.2471/BLT.18.030218,PMC5791787,29403110,CC BY,Marion Koopmans tells Fiona Fleck why the world needs a publicly-funded network of hubs in all regions with local experts able to respond to infectious disease threats as they emerge.,2018 Feb 1,,Bull World Health Organ,,,False
e43ae4e86302c1a05c8a22675a192245626fa9ac,PMC,Can long-term historical data from electronic medical records improve surveillance for epidemics of acute respiratory infections? A systematic evaluation,http://dx.doi.org/10.1371/journal.pone.0191324,PMC5791979,29385161,CC0,"BACKGROUND: As the deployment of electronic medical records (EMR) expands, so is the availability of long-term datasets that could serve to enhance public health surveillance. We hypothesized that EMR-based surveillance systems that incorporate seasonality and other long-term trends would discover outbreaks of acute respiratory infections (ARI) sooner than systems that only consider the recent past. METHODS: We simulated surveillance systems aimed at discovering modeled influenza outbreaks injected into backgrounds of patients with ARI. Backgrounds of daily case counts were either synthesized or obtained by applying one of three previously validated ARI case-detection algorithms to authentic EMR entries. From the time of outbreak injection, detection statistics were applied daily on paired background+injection and background-only time series. The relationship between the detection delay (the time from injection to the first alarm uniquely found in the background+injection data) and the false-alarm rate (FAR) was determined by systematically varying the statistical alarm threshold. We compared this relationship for outbreak detection methods that utilized either 7 days (early aberrancy reporting system (EARS)) or 2–4 years of past data (seasonal autoregressive integrated moving average (SARIMA) time series modeling). RESULTS: In otherwise identical surveillance systems, SARIMA detected epidemics sooner than EARS at any FAR below 10%. The algorithms used to detect single ARI cases impacted both the feasibility and marginal benefits of SARIMA modeling. Under plausible real-world conditions, SARIMA could reduce detection delay by 5–16 days. It also was more sensitive at detecting the summer wave of the 2009 influenza pandemic. CONCLUSION: Time series modeling of long-term historical EMR data can reduce the time it takes to discover epidemics of ARI. Realistic surveillance simulations may prove invaluable to optimize system design and tuning.",2018 Jan 31,"['Zheng, Hongzhang', 'Woodall, William H.', 'Carlson, Abigail L.', 'DeLisle, Sylvain']",PLoS One,,,True
5b470094ead1416c283ca042644ac1061103b101,PMC,Understanding the legal trade of cattle and camels and the derived risk of Rift Valley Fever introduction into and transmission within Egypt,http://dx.doi.org/10.1371/journal.pntd.0006143,PMC5792020,29351273,CC BY,"Rift Valley Fever (RVF) is a mosquito-borne zoonosis, which may cause significant losses for the livestock sector and have serious public health implications. Egypt has been repeatedly affected by RVF epidemics, mainly associated to the importation of animals from sub-Saharan countries, where the disease is endemic. The objective of our study was the improvement of the surveillance and control strategies implemented in Egypt. In order to do that, first we evaluated the legal trade of live animals into and within Egypt. Then, we assessed the risk of Rift Valley Fever virus (RVFV) transmission within the country using a multi-criteria evaluation approach. Finally, we combined the animal trade and the risk of RVFV transmission data to identify those areas and periods in which the introduction of RVFV is more likely. Our results indicate that the main risk of RVFV introduction is posed by the continuous flow of large number of camels coming from Sudan. The risk of RVFV transmission by vectors is restricted to the areas surrounding the Nile river, and does not vary significantly throughout the year. Imported camels are taken to quarantines, where the risk of RVFV transmission by vectors is generally low. Then, they are taken to animal markets or slaughterhouses, many located in populated areas, where the risk of RVFV transmission to animals or humans is much higher. The measures currently implemented (quarantines, vaccination or testing) seem to have a limited effect in reducing the risk of RVFV introduction, and therefore other (risk-based) surveillance strategies are proposed.",2018 Jan 19,"['Napp, Sebastian', 'Chevalier, Veronique', 'Busquets, Núria', 'Calistri, Paolo', 'Casal, Jordi', 'Attia, Mohamed', 'Elbassal, Rehab', 'Hosni, Heba', 'Farrag, Hatem', 'Hassan, Noura', 'Tawfik, Rasha', 'Abd Elkader, Sohair', 'Bayomy, Shahin']",PLoS Negl Trop Dis,,,True
37c5a8f3c1c22335e7a3569c243cf4185295fc54,PMC,Ghosts of infections past: using archival samples to understand a century of monkeypox virus prevalence among host communities across space and time,http://dx.doi.org/10.1098/rsos.171089,PMC5792900,29410823,CC BY,"Infectious diseases that originate from multiple wildlife hosts can be complex and problematic to manage. A full understanding is further limited by large temporal and spatial gaps in sampling. However, these limitations can be overcome, in part, by using historical samples, such as those derived from museum collections. Here, we screened over 1000 museum specimens collected over the past 120 years to examine the historical distribution and prevalence of monkeypox virus (MPXV) in five species of African rope squirrel (Funisciurus sp.) collected across Central Africa. We found evidence of MPXV infections in host species as early as 1899, half a century earlier than the first recognized case of MPXV in 1958, supporting the suggestion that historic pox-like outbreaks in humans and non-human primates may have been caused by MPXV rather than smallpox as originally thought. MPX viral DNA was found in 93 of 1038 (9.0%) specimens from five Funisciurus species (F. anerythrus, F. carruthersi, F. congicus, F. lemniscatus and F. pyrropus), of which F. carruthersi and pyrropus had not previously been identified as potential MPXV hosts. We additionally documented relative prevalence rates of infection in museum specimens of Funisciurus and examined the spatial and temporal distribution of MPXV in these potential host species across nearly a hundred years (1899–1993).",2018 Jan 31,"['Tiee, Madeline S.', 'Harrigan, Ryan J.', 'Thomassen, Henri A.', 'Smith, Thomas B.']",R Soc Open Sci,,,True
8a321781f47b4e89b93b2cb41412dbb8578c9cfd,PMC,Ghosts of infections past: using archival samples to understand a century of monkeypox virus prevalence among host communities across space and time,http://dx.doi.org/10.1098/rsos.171089,PMC5792900,29410823,CC BY,"Infectious diseases that originate from multiple wildlife hosts can be complex and problematic to manage. A full understanding is further limited by large temporal and spatial gaps in sampling. However, these limitations can be overcome, in part, by using historical samples, such as those derived from museum collections. Here, we screened over 1000 museum specimens collected over the past 120 years to examine the historical distribution and prevalence of monkeypox virus (MPXV) in five species of African rope squirrel (Funisciurus sp.) collected across Central Africa. We found evidence of MPXV infections in host species as early as 1899, half a century earlier than the first recognized case of MPXV in 1958, supporting the suggestion that historic pox-like outbreaks in humans and non-human primates may have been caused by MPXV rather than smallpox as originally thought. MPX viral DNA was found in 93 of 1038 (9.0%) specimens from five Funisciurus species (F. anerythrus, F. carruthersi, F. congicus, F. lemniscatus and F. pyrropus), of which F. carruthersi and pyrropus had not previously been identified as potential MPXV hosts. We additionally documented relative prevalence rates of infection in museum specimens of Funisciurus and examined the spatial and temporal distribution of MPXV in these potential host species across nearly a hundred years (1899–1993).",2018 Jan 31,"['Tiee, Madeline S.', 'Harrigan, Ryan J.', 'Thomassen, Henri A.', 'Smith, Thomas B.']",R Soc Open Sci,,,False
3630a298cf2f551b0bfa82c26288456e13fa5a2e,PMC,Ghosts of infections past: using archival samples to understand a century of monkeypox virus prevalence among host communities across space and time,http://dx.doi.org/10.1098/rsos.171089,PMC5792900,29410823,CC BY,"Infectious diseases that originate from multiple wildlife hosts can be complex and problematic to manage. A full understanding is further limited by large temporal and spatial gaps in sampling. However, these limitations can be overcome, in part, by using historical samples, such as those derived from museum collections. Here, we screened over 1000 museum specimens collected over the past 120 years to examine the historical distribution and prevalence of monkeypox virus (MPXV) in five species of African rope squirrel (Funisciurus sp.) collected across Central Africa. We found evidence of MPXV infections in host species as early as 1899, half a century earlier than the first recognized case of MPXV in 1958, supporting the suggestion that historic pox-like outbreaks in humans and non-human primates may have been caused by MPXV rather than smallpox as originally thought. MPX viral DNA was found in 93 of 1038 (9.0%) specimens from five Funisciurus species (F. anerythrus, F. carruthersi, F. congicus, F. lemniscatus and F. pyrropus), of which F. carruthersi and pyrropus had not previously been identified as potential MPXV hosts. We additionally documented relative prevalence rates of infection in museum specimens of Funisciurus and examined the spatial and temporal distribution of MPXV in these potential host species across nearly a hundred years (1899–1993).",2018 Jan 31,"['Tiee, Madeline S.', 'Harrigan, Ryan J.', 'Thomassen, Henri A.', 'Smith, Thomas B.']",R Soc Open Sci,,,False
e45649934b47f4f1f832ea0af1a91f78d416cdf0,PMC,Ghosts of infections past: using archival samples to understand a century of monkeypox virus prevalence among host communities across space and time,http://dx.doi.org/10.1098/rsos.171089,PMC5792900,29410823,CC BY,"Infectious diseases that originate from multiple wildlife hosts can be complex and problematic to manage. A full understanding is further limited by large temporal and spatial gaps in sampling. However, these limitations can be overcome, in part, by using historical samples, such as those derived from museum collections. Here, we screened over 1000 museum specimens collected over the past 120 years to examine the historical distribution and prevalence of monkeypox virus (MPXV) in five species of African rope squirrel (Funisciurus sp.) collected across Central Africa. We found evidence of MPXV infections in host species as early as 1899, half a century earlier than the first recognized case of MPXV in 1958, supporting the suggestion that historic pox-like outbreaks in humans and non-human primates may have been caused by MPXV rather than smallpox as originally thought. MPX viral DNA was found in 93 of 1038 (9.0%) specimens from five Funisciurus species (F. anerythrus, F. carruthersi, F. congicus, F. lemniscatus and F. pyrropus), of which F. carruthersi and pyrropus had not previously been identified as potential MPXV hosts. We additionally documented relative prevalence rates of infection in museum specimens of Funisciurus and examined the spatial and temporal distribution of MPXV in these potential host species across nearly a hundred years (1899–1993).",2018 Jan 31,"['Tiee, Madeline S.', 'Harrigan, Ryan J.', 'Thomassen, Henri A.', 'Smith, Thomas B.']",R Soc Open Sci,,,False
0a0039915ff7f6876693d65aa6121d10849aecdb,PMC,Ghosts of infections past: using archival samples to understand a century of monkeypox virus prevalence among host communities across space and time,http://dx.doi.org/10.1098/rsos.171089,PMC5792900,29410823,CC BY,"Infectious diseases that originate from multiple wildlife hosts can be complex and problematic to manage. A full understanding is further limited by large temporal and spatial gaps in sampling. However, these limitations can be overcome, in part, by using historical samples, such as those derived from museum collections. Here, we screened over 1000 museum specimens collected over the past 120 years to examine the historical distribution and prevalence of monkeypox virus (MPXV) in five species of African rope squirrel (Funisciurus sp.) collected across Central Africa. We found evidence of MPXV infections in host species as early as 1899, half a century earlier than the first recognized case of MPXV in 1958, supporting the suggestion that historic pox-like outbreaks in humans and non-human primates may have been caused by MPXV rather than smallpox as originally thought. MPX viral DNA was found in 93 of 1038 (9.0%) specimens from five Funisciurus species (F. anerythrus, F. carruthersi, F. congicus, F. lemniscatus and F. pyrropus), of which F. carruthersi and pyrropus had not previously been identified as potential MPXV hosts. We additionally documented relative prevalence rates of infection in museum specimens of Funisciurus and examined the spatial and temporal distribution of MPXV in these potential host species across nearly a hundred years (1899–1993).",2018 Jan 31,"['Tiee, Madeline S.', 'Harrigan, Ryan J.', 'Thomassen, Henri A.', 'Smith, Thomas B.']",R Soc Open Sci,,,False
ccc9f9d0c39e42e6c56cec45484690417a7e8323,PMC,Ghosts of infections past: using archival samples to understand a century of monkeypox virus prevalence among host communities across space and time,http://dx.doi.org/10.1098/rsos.171089,PMC5792900,29410823,CC BY,"Infectious diseases that originate from multiple wildlife hosts can be complex and problematic to manage. A full understanding is further limited by large temporal and spatial gaps in sampling. However, these limitations can be overcome, in part, by using historical samples, such as those derived from museum collections. Here, we screened over 1000 museum specimens collected over the past 120 years to examine the historical distribution and prevalence of monkeypox virus (MPXV) in five species of African rope squirrel (Funisciurus sp.) collected across Central Africa. We found evidence of MPXV infections in host species as early as 1899, half a century earlier than the first recognized case of MPXV in 1958, supporting the suggestion that historic pox-like outbreaks in humans and non-human primates may have been caused by MPXV rather than smallpox as originally thought. MPX viral DNA was found in 93 of 1038 (9.0%) specimens from five Funisciurus species (F. anerythrus, F. carruthersi, F. congicus, F. lemniscatus and F. pyrropus), of which F. carruthersi and pyrropus had not previously been identified as potential MPXV hosts. We additionally documented relative prevalence rates of infection in museum specimens of Funisciurus and examined the spatial and temporal distribution of MPXV in these potential host species across nearly a hundred years (1899–1993).",2018 Jan 31,"['Tiee, Madeline S.', 'Harrigan, Ryan J.', 'Thomassen, Henri A.', 'Smith, Thomas B.']",R Soc Open Sci,,,False
10dab751e09a2f4ef5a81f68b82c76c8be09343f,PMC,Experimental evidence of a pathogen invasion threshold,http://dx.doi.org/10.1098/rsos.171975,PMC5792953,29410876,CC BY,"Host density thresholds to pathogen invasion separate regions of parameter space corresponding to endemic and disease-free states. The host density threshold is a central concept in theoretical epidemiology and a common target of human and wildlife disease control programmes, but there is mixed evidence supporting the existence of thresholds, especially in wildlife populations or for pathogens with complex transmission modes (e.g. environmental transmission). Here, we demonstrate the existence of a host density threshold for an environmentally transmitted pathogen by combining an epidemiological model with a microcosm experiment. Experimental epidemics consisted of replicate populations of naive crustacean zooplankton (Daphnia dentifera) hosts across a range of host densities (20–640 hosts l(−1)) that were exposed to an environmentally transmitted fungal pathogen (Metschnikowia bicuspidata). Epidemiological model simulations, parametrized independently of the experiment, qualitatively predicted experimental pathogen invasion thresholds. Variability in parameter estimates did not strongly influence outcomes, though systematic changes to key parameters have the potential to shift pathogen invasion thresholds. In summary, we provide one of the first clear experimental demonstrations of pathogen invasion thresholds in a replicated experimental system, and provide evidence that such thresholds may be predictable using independently constructed epidemiological models.",2018 Jan 24,"['Dallas, Tad A.', 'Krkošek, Martin', 'Drake, John M.']",R Soc Open Sci,,,True
afa0cf3bd7286376ed6c62033c05a5b6d9e4211f,PMC,Experimental evidence of a pathogen invasion threshold,http://dx.doi.org/10.1098/rsos.171975,PMC5792953,29410876,CC BY,"Host density thresholds to pathogen invasion separate regions of parameter space corresponding to endemic and disease-free states. The host density threshold is a central concept in theoretical epidemiology and a common target of human and wildlife disease control programmes, but there is mixed evidence supporting the existence of thresholds, especially in wildlife populations or for pathogens with complex transmission modes (e.g. environmental transmission). Here, we demonstrate the existence of a host density threshold for an environmentally transmitted pathogen by combining an epidemiological model with a microcosm experiment. Experimental epidemics consisted of replicate populations of naive crustacean zooplankton (Daphnia dentifera) hosts across a range of host densities (20–640 hosts l(−1)) that were exposed to an environmentally transmitted fungal pathogen (Metschnikowia bicuspidata). Epidemiological model simulations, parametrized independently of the experiment, qualitatively predicted experimental pathogen invasion thresholds. Variability in parameter estimates did not strongly influence outcomes, though systematic changes to key parameters have the potential to shift pathogen invasion thresholds. In summary, we provide one of the first clear experimental demonstrations of pathogen invasion thresholds in a replicated experimental system, and provide evidence that such thresholds may be predictable using independently constructed epidemiological models.",2018 Jan 24,"['Dallas, Tad A.', 'Krkošek, Martin', 'Drake, John M.']",R Soc Open Sci,,,True
356b49eeee107ff0397b374e29cdd8f133b2688f,PMC,Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients,http://dx.doi.org/10.1371/journal.pone.0192024,PMC5794141,29389944,CC BY,"von Willebrand factor (VWF) levels in healthy individuals and in patients with type 1 von Willebrand disease (VWD) are influenced by genetic variation in several genes, e.g. VWF, ABO, STXBP5 and CLEC4M. This study aims to screen comprehensively for CLEC4M variants and investigate their association with type 1 VWD in the Swedish population. In order to screen for CLEC4M variants, the CLEC4M gene region was re-sequenced and the polymorphic neck region was genotyped in 106 type 1 VWD patients from unrelated type 1 VWD families. Single nucleotide variants (SNV) and variable number tandem repeat (VNTR) allele and genotype frequencies were then compared with 294 individuals from the 1000Genomes project and 436 Swedish control individuals. Re-sequencing identified a total of 42 SNVs. Rare variants showed no accumulation in type 1 VWD patients and are not thought to contribute substantially to type 1 VWD. The only missense mutation (rs2277998, NP_001138379.1:p.Asp224Asn) had a higher frequency in type 1 VWD patients than in controls (4.9%). The VNTR genotypes 57 and 67 were observed at higher frequencies than expected in type 1 VWD patients (6.4% and 6.2%) and showed an increase in patients compared with controls (7.4% and 3.1%). Strong linkage disequilibrium in the CLEC4M region makes it difficult to distinguish between the effect of the missense mutation and the VNTR genotypes. In conclusion, heterozygous VNTR genotypes 57 and 67 of CLEC4M were highly enriched and are the most likely mechanism through which CLEC4M contributes to disease in the Swedish type 1 VWD population.",2018 Feb 1,"['Manderstedt, Eric', 'Lind-Halldén, Christina', 'Lethagen, Stefan', 'Halldén, Christer']",PLoS One,,,True
39ac63ed0923e3bc5533c2f7998d5b62a828173a,PMC,SMARCA2-regulated host cell factors are required for MxA restriction of influenza A viruses,http://dx.doi.org/10.1038/s41598-018-20458-2,PMC5794779,29391557,CC BY,"The human interferon (IFN)-induced MxA protein is a key antiviral host restriction factor exhibiting broad antiviral activity against many RNA viruses, including highly pathogenic avian influenza A viruses (IAV) of the H5N1 and H7N7 subtype. To date the mechanism for how MxA exerts its antiviral activity is unclear, however, additional cellular factors are believed to be essential for this activity. To identify MxA cofactors we performed a genome-wide siRNA-based screen in human airway epithelial cells (A549) constitutively expressing MxA using an H5N1 reporter virus. These data were complemented with a proteomic screen to identify MxA-interacting proteins. The combined data identified SMARCA2, the ATPase subunit of the BAF chromatin remodeling complex, as a crucial factor required for the antiviral activity of MxA against IAV. Intriguingly, our data demonstrate that although SMARCA2 is essential for expression of some IFN-stimulated genes (ISGs), and the establishment of an antiviral state, it is not required for expression of MxA, suggesting an indirect effect on MxA activity. Transcriptome analysis of SMARCA2-depleted A549-MxA cells identified a small set of SMARCA2-regulated factors required for activity of MxA, in particular IFITM2 and IGFBP3. These findings reveal that several virus-inducible factors work in concert to enable MxA restriction of IAV.",2018 Feb 1,"['Dornfeld, Dominik', 'Dudek, Alexandra H.', 'Vausselin, Thibaut', 'Günther, Sira C.', 'Hultquist, Judd F.', 'Giese, Sebastian', 'Khokhlova-Cubberley, Daria', 'Chew, Yap C.', 'Pache, Lars', 'Krogan, Nevan J.', 'Garcia-Sastre, Adolfo', 'Schwemmle, Martin', 'Shaw, Megan L.']",Sci Rep,,,True
25621281691205eb015383cbac839182b838514f,PMC,SMARCA2-regulated host cell factors are required for MxA restriction of influenza A viruses,http://dx.doi.org/10.1038/s41598-018-20458-2,PMC5794779,29391557,CC BY,"The human interferon (IFN)-induced MxA protein is a key antiviral host restriction factor exhibiting broad antiviral activity against many RNA viruses, including highly pathogenic avian influenza A viruses (IAV) of the H5N1 and H7N7 subtype. To date the mechanism for how MxA exerts its antiviral activity is unclear, however, additional cellular factors are believed to be essential for this activity. To identify MxA cofactors we performed a genome-wide siRNA-based screen in human airway epithelial cells (A549) constitutively expressing MxA using an H5N1 reporter virus. These data were complemented with a proteomic screen to identify MxA-interacting proteins. The combined data identified SMARCA2, the ATPase subunit of the BAF chromatin remodeling complex, as a crucial factor required for the antiviral activity of MxA against IAV. Intriguingly, our data demonstrate that although SMARCA2 is essential for expression of some IFN-stimulated genes (ISGs), and the establishment of an antiviral state, it is not required for expression of MxA, suggesting an indirect effect on MxA activity. Transcriptome analysis of SMARCA2-depleted A549-MxA cells identified a small set of SMARCA2-regulated factors required for activity of MxA, in particular IFITM2 and IGFBP3. These findings reveal that several virus-inducible factors work in concert to enable MxA restriction of IAV.",2018 Feb 1,"['Dornfeld, Dominik', 'Dudek, Alexandra H.', 'Vausselin, Thibaut', 'Günther, Sira C.', 'Hultquist, Judd F.', 'Giese, Sebastian', 'Khokhlova-Cubberley, Daria', 'Chew, Yap C.', 'Pache, Lars', 'Krogan, Nevan J.', 'Garcia-Sastre, Adolfo', 'Schwemmle, Martin', 'Shaw, Megan L.']",Sci Rep,,,True
ad6a3623db73b778bbfabb99c47116c30459e66d,PMC,Auxiliary activation of the complement system and its importance for the pathophysiology of clinical conditions,http://dx.doi.org/10.1007/s00281-017-0646-9,PMC5794838,28900700,CC BY,"Activation and regulation of the cascade systems of the blood (the complement system, the coagulation/contact activation/kallikrein system, and the fibrinolytic system) occurs via activation of zymogen molecules to specific active proteolytic enzymes. Despite the fact that the generated proteases are all present together in the blood, under physiological conditions, the activity of the generated proteases is controlled by endogenous protease inhibitors. Consequently, there is remarkable little crosstalk between the different systems in the fluid phase. This concept review article aims at identifying and describing conditions where the strict system-related control is circumvented. These include clinical settings where massive amounts of proteolytic enzymes are released from tissues, e.g., during pancreatitis or post-traumatic tissue damage, resulting in consumption of the natural substrates of the specific proteases and the available protease inhibitor. Another example of cascade system dysregulation is disseminated intravascular coagulation, with canonical activation of all cascade systems of the blood, also leading to specific substrate and protease inhibitor elimination. The present review explains basic concepts in protease biochemistry of importance to understand clinical conditions with extensive protease activation.",2018 Sep 12,"['Huber-Lang, Markus', 'Ekdahl, Kristina N.', 'Wiegner, Rebecca', 'Fromell, Karin', 'Nilsson, Bo']",Semin Immunopathol,,,True
ccb21efaed2edb86c05dd860b5f61beaf856e2a8,PMC,Pregnancy and infection: using disease pathogenesis to inform vaccine strategy,http://dx.doi.org/10.1038/s41541-017-0042-4,PMC5794984,29423318,CC BY,"Vaccination is the mainstay of preventative medicine for many infectious diseases. Pregnant women, unborn fetuses, and neonates represent three at-risk populations that can be simultaneously protected by strategic vaccination protocols. Because the pathogenesis of different infectious microbes varies based on tissue tropism, timing of infection, and host susceptibility, the goals of immunization are not uniform across all vaccines. Mechanistic understanding of infectious disease pathogenesis and immune responses is therefore essential to inform vaccine design and the implementation of appropriate immunization protocols that optimize protection of pregnant women, fetuses, and neonates.",2018 Feb 1,"['Vermillion, Meghan S.', 'Klein, Sabra L.']",NPJ Vaccines,,,True
cbb97774bf1adc0c1465970bcdabcd43ce0b365d,PMC,Human metapneumovirus - what we know now,http://dx.doi.org/10.12688/f1000research.12625.1,PMC5795268,29744035,CC BY,"Human metapneumovirus (HMPV) is a leading cause of acute respiratory infection, particularly in children, immunocompromised patients, and the elderly. HMPV, which is closely related to avian metapneumovirus subtype C, has circulated for at least 65 years, and nearly every child will be infected with HMPV by the age of 5. However, immunity is incomplete, and re-infections occur throughout adult life. Symptoms are similar to those of other respiratory viral infections, ranging from mild (cough, rhinorrhea, and fever) to more severe (bronchiolitis and pneumonia). The preferred method for diagnosis is reverse transcription-polymerase chain reaction as HMPV is difficult to culture. Although there have been many advances made in the past 16 years since its discovery, there are still no US Food and Drug Administration-approved antivirals or vaccines available to treat HMPV. Both small animal and non-human primate models have been established for the study of HMPV. This review will focus on the epidemiology, transmission, and clinical manifestations in humans as well as the animal models of HMPV pathogenesis and host immune response.",2018 Feb 1,"['Shafagati, Nazly', 'Williams, John']",F1000Res,,,True
bc91f45d3fb7fbedebffb850dbf2dc3d3c7c2142,PMC,"microRNA-4331 Promotes Transmissible Gastroenteritis Virus (TGEV)-induced Mitochondrial Damage Via Targeting RB1, Upregulating Interleukin-1 Receptor Accessory Protein (IL1RAP), and Activating p38 MAPK Pathway In Vitro",http://dx.doi.org/10.1074/mcp.RA117.000432,PMC5795386,29217619,CC BY,"Transmissible gastroenteritis virus (TGEV), a member of the coronaviridae family, could cause fatal diarrhea of piglets and result in numerous economic losses. Previous studies demonstrated that TGEV infection could lead to mitochondrial damage and upregulate miR-4331 level. So miR-4331 may play an important regulatory role in the control of mitochondrial function. To explore the potential role of miR-4331 in mitochondrial damage, we adopted a strategy consisting of quantitative proteomic analysis of porcine kidney (PK-15) cells in response to miR-4331 and TGEV infection. Eventually, 69 differentially expressed proteins were gained. The target of miR-4331 was identified. The effects of miR-4331 and its target RB1 on mitochondrial Ca(2+) level, mitochondrial membrane potential (MMP), interleukin-1 receptor accessory protein (IL1RAP), p38 MAPK signaling pathway were investigated. The results showed that miR-4331 elevated mitochondrial Ca(2+) level, reduced MMP, targets Retinoblastoma 1 (RB1), upregulated IL1RAP, and induced activation of p38 MAPK pathway during TGEV infection. RB1 was identified as the direct targets of miR-4331 and downregulated IL1RAP, suppressed the activation of p38 MPAK, and attenuated TGEV-induced mitochondrial damage. In addition, IL1RAP played a positive role in activating p38 MAPK signaling and negative role in TGEV-induced mitochondrial damage. The data indicate that miR-4331 aggravates TGEV-induced mitochondrial damage by repressing expression of RB1, promoting IL1RAP, and activating p38 MAPK pathway.",2018 Feb 7,"['Zhao, Xiaomin', 'Bai, Xiaoyuan', 'Guan, Lijuan', 'Li, Juejun', 'Song, Xiangjun', 'Ma, Xuelian', 'Guo, Jianxiong', 'Zhang, Zhichao', 'Du, Qian', 'Huang, Yong', 'Tong, Dewen']",Mol Cell Proteomics,,,True
11416bee008daf3c42621002ba7f3a6939601b0d,PMC,High-Mannose But Not Complex-Type Glycosylation of Tetherin Is Required for Restriction of HIV-1 Release,http://dx.doi.org/10.3390/v10010026,PMC5795439,29303997,CC BY,"Tetherin is an interferon-inducible antiviral protein that inhibits the release of a broad spectrum of enveloped viruses by retaining virions at the surface of infected cells. While the role of specific tetherin domains in antiviral activity is clearly established, the role of glycosylation in tetherin function is not clear. In this study, we carried out a detailed investigation of this question by using tetherin variants in which one or both sites of N-linked glycosylation were mutated (N65A, N92A, and N65,92A), and chemical inhibitors that prevent glycosylation at specific stages of oligosaccharide were added or modified. The single N-linked glycosylation mutants, N65A and N92A, efficiently inhibited the release of Vpu-defective human immunodeficiency virus type 1 (HIV-1). In contrast, the non-glycosylated double mutant, N65,92A, lost its ability to block HIV-1 release. The inability of the N65,92A mutant to inhibit HIV-1 release is associated with a lack of cell-surface expression. A role for glycosylation in cell-surface tetherin expression is supported by tunicamycin treatment, which inhibits the first step of N-linked glycosylation and impairs both cell-surface expression and antiviral activity. Inhibition of complex-type glycosylation with kifunensine, an inhibitor of the oligosaccharide processing enzyme mannosidase 1, had no effect on either the cell-surface expression or antiviral activity of tetherin. These results demonstrate that high-mannose modification of a single asparagine residue is necessary and sufficient, while complex-type glycosylation is dispensable, for cell-surface tetherin expression and antiviral activity.",2018 Jan 5,"['Waheed, Abdul A.', 'Gitzen, Ariana', 'Swiderski, Maya', 'Freed, Eric O.']",Viruses,,,True
502fc7e74c22bd0763542416c09589b5dca35b75,PMC,Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface,http://dx.doi.org/10.3390/v10010028,PMC5795441,29316722,CC BY,"Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.",2018 Jan 8,"['Knodel, Markus M.', 'Nägel, Arne', 'Reiter, Sebastian', 'Vogel, Andreas', 'Targett-Adams, Paul', 'McLauchlan, John', 'Herrmann, Eva', 'Wittum, Gabriel']",Viruses,,,True
31f30e0bd74035d9bbae69437e8af989fa78966c,PMC,Interferons: Reprogramming the Metabolic Network against Viral Infection,http://dx.doi.org/10.3390/v10010036,PMC5795449,29342871,CC BY,"Viruses exploit the host and induce drastic metabolic changes to ensure an optimal environment for replication and the production of viral progenies. In response, the host has developed diverse countermeasures to sense and limit these alterations to combat viral infection. One such host mechanism is through interferon signaling. Interferons are cytokines that enhances the transcription of hundreds of interferon-stimulated genes (ISGs) whose products are key players in the innate immune response to viral infection. In addition to their direct targeting of viral components, interferons and ISGs exert profound effects on cellular metabolism. Recent studies have started to illuminate on the specific role of interferon in rewiring cellular metabolism to activate immune cells and limit viral infection. This review reflects on our current understanding of the complex networking that occurs between the virus and host at the interface of cellular metabolism, with a focus on the ISGs in particular, cholesterol-25-hydroxylase (CH25H), spermidine/spermine acetyltransferase 1 (SAT1), indoleamine-2,3-dioxygenase (IDO1) and sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1), which were recently discovered to modulate specific metabolic events and consequently deter viral infection.",2018 Jan 13,"['Raniga, Kavita', 'Liang, Chen']",Viruses,,,True
e7b9c386495606981ed7a87be8a325c87c35fef9,PMC,CRISPR-Cas Targeting of Host Genes as an Antiviral Strategy,http://dx.doi.org/10.3390/v10010040,PMC5795453,29337866,CC BY,"Currently, a new gene editing tool—the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated (Cas) system—is becoming a promising approach for genetic manipulation at the genomic level. This simple method, originating from the adaptive immune defense system in prokaryotes, has been developed and applied to antiviral research in humans. Based on the characteristics of virus-host interactions and the basic rules of nucleic acid cleavage or gene activation of the CRISPR-Cas system, it can be used to target both the virus genome and host factors to clear viral reservoirs and prohibit virus infection or replication. Here, we summarize recent progress of the CRISPR-Cas technology in editing host genes as an antiviral strategy.",2018 Jan 16,"['Chen, Shuliang', 'Yu, Xiao', 'Guo, Deyin']",Viruses,,,True
09cba4ea15eda3c3bd33243487c9bd32928d9635,PMC,Identification of Secreted Proteins Involved in Nonspecific dsRNA-Mediated Lutzomyia longipalpis LL5 Cell Antiviral Response,http://dx.doi.org/10.3390/v10010043,PMC5795456,29346269,CC BY,"Hematophagous insects transmit infectious diseases. Sand flies are vectors of leishmaniasis, but can also transmit viruses. We have been studying immune responses of Lutzomyia longipalpis, the main vector of visceral leishmaniasis in the Americas. We identified a non-specific antiviral response in L. longipalpis LL5 embryonic cells when treated with non-specific double-stranded RNAs (dsRNAs). This response is reminiscent of interferon response in mammals. We are investigating putative effectors for this antiviral response. Secreted molecules have been implicated in immune responses, including interferon-related responses. We conducted a mass spectrometry analysis of conditioned medium from LL5 cells 24 and 48 h after dsRNA or mock treatment. We identified 304 proteins. At 24 h, 19 proteins had an abundance equal or greater than 2-fold change, while the levels of 17 proteins were reduced when compared to control cells. At the 48 h time point, these numbers were 33 and 71, respectively. The two most abundant secreted peptides at 24 h in the dsRNA-transfected group were phospholipid scramblase, an interferon-inducible protein that mediates antiviral activity, and forskolin-binding protein (FKBP), a member of the immunophilin family, which mediates the effect of immunosuppressive drugs. The transcription profile of most candidates did not follow the pattern of secreted protein abundance.",2018 Jan 18,"['Martins-da-Silva, Andrea', 'Telleria, Erich Loza', 'Batista, Michel', 'Marchini, Fabricio Klerynton', 'Traub-Csekö, Yara Maria', 'Tempone, Antonio Jorge']",Viruses,,,True
441421494c2a4ed45a8d6b711842ed8ee43ec038,PMC,Free-Form Deformation Approach for Registration of Visible and Infrared Facial Images in Fever Screening †,http://dx.doi.org/10.3390/s18010125,PMC5795541,29300320,CC BY,"Fever screening based on infrared (IR) thermographs (IRTs) is an approach that has been implemented during infectious disease pandemics, such as Ebola and Severe Acute Respiratory Syndrome. A recently published international standard indicates that regions medially adjacent to the inner canthi provide accurate estimates of core body temperature and are preferred sites for fever screening. Therefore, rapid, automated identification of the canthi regions within facial IR images may greatly facilitate rapid fever screening of asymptomatic travelers. However, it is more difficult to accurately identify the canthi regions from IR images than from visible images that are rich with exploitable features. In this study, we developed and evaluated techniques for multi-modality image registration (MMIR) of simultaneously captured visible and IR facial images for fever screening. We used free form deformation (FFD) models based on edge maps to improve registration accuracy after an affine transformation. Two widely used FFD models in medical image registration based on the Demons and cubic B-spline algorithms were qualitatively compared. The results showed that the Demons algorithm outperformed the cubic B-spline algorithm, likely due to overfitting of outliers by the latter method. The quantitative measure of registration accuracy, obtained through selected control point correspondence, was within 2.8 ± 1.2 mm, which enables accurate and automatic localization of canthi regions in the IR images for temperature measurement.",2018 Jan 4,"['Dwith Chenna, Yedukondala Narendra', 'Ghassemi, Pejhman', 'Pfefer, T. Joshua', 'Casamento, Jon', 'Wang, Quanzeng']",Sensors (Basel),,,True
6b5fd83b8ea551e2637d8291e2f74ed9113b92ab,PMC,A Fully Integrated Paper-Microfluidic Electrochemical Device for Simultaneous Analysis of Physiologic Blood Ions,http://dx.doi.org/10.3390/s18010104,PMC5796313,29301270,CC BY,"A fully integrated paper microfluidic electrochemical device equipped with three different cation permeable films is developed to determine blood ions (Cl(−), Na(+), K(+), and Ca(2+)) at a time. These blood ions that are normally dissolved in the real human blood stream are essential for cell metabolisms and homeostasis in the human body. Abnormal concentration of blood ions causes many serious disorders. The optimized microfluidic device working without any external power source can directly and effectively separate human blood components, and subsequently detect a specific blood ion with minimized interference. The measured sensitivity to Cl(−), K(+), Na(+), and Ca(2+) are −47.71, 45.97, 51.06, and 19.46 in mV decade(−1), respectively. Potentiometric responses of the microfluidic devices to blood serum samples are in the normal ranges of each cation, and comparable with responses from the commercial blood ion analyzer Abbott i-Stat.",2018 Jan 1,"['Jin, Joon-Hyung', 'Kim, Joon Hyub', 'Lee, Sang Ki', 'Choi, Sam Jin', 'Park, Chan Won', 'Min, Nam Ki']",Sensors (Basel),,,True
7d9088628f9e40bb65ee8e1a6a25cc0007d3f614,PMC,A Fully Integrated Paper-Microfluidic Electrochemical Device for Simultaneous Analysis of Physiologic Blood Ions,http://dx.doi.org/10.3390/s18010104,PMC5796313,29301270,CC BY,"A fully integrated paper microfluidic electrochemical device equipped with three different cation permeable films is developed to determine blood ions (Cl(−), Na(+), K(+), and Ca(2+)) at a time. These blood ions that are normally dissolved in the real human blood stream are essential for cell metabolisms and homeostasis in the human body. Abnormal concentration of blood ions causes many serious disorders. The optimized microfluidic device working without any external power source can directly and effectively separate human blood components, and subsequently detect a specific blood ion with minimized interference. The measured sensitivity to Cl(−), K(+), Na(+), and Ca(2+) are −47.71, 45.97, 51.06, and 19.46 in mV decade(−1), respectively. Potentiometric responses of the microfluidic devices to blood serum samples are in the normal ranges of each cation, and comparable with responses from the commercial blood ion analyzer Abbott i-Stat.",2018 Jan 1,"['Jin, Joon-Hyung', 'Kim, Joon Hyub', 'Lee, Sang Ki', 'Choi, Sam Jin', 'Park, Chan Won', 'Min, Nam Ki']",Sensors (Basel),,,False
ae97b438b672fe77deda33d0f617f47a2102966c,PMC,Efficacy of genogroup 1 based porcine epidemic diarrhea live vaccine against genogroup 2 field strain in Japan,http://dx.doi.org/10.1186/s12985-018-0940-8,PMC5797392,29394943,CC BY,"BACKGROUND: Porcine epidemic diarrhea (PED) is a lethal infectious disease in suckling piglets with symptoms including watery diarrhea caused by PED virus (PEDV). Since the late 1990’s, live vaccines based on genogroup 1 virus have been used in Japan, and a significant amount of the vaccine has been used even after new genogroups invaded in 2013. In this study, we evaluated the effect of a conventional PED live vaccine on a newly prevalent genogroup 2 field strain in experimental and field situations. METHODS: Two pregnant sows were administered twice the live vaccine before farrowing. A pregnant sow was served as a negative control. All newborn piglets were challenged with the genogroup 2 virus, and clinical signs were monitored for 7 days post challenge. PEDV-specific immune responses in serum and milk of the sows were assayed by virus neutralization assay. The efficacy of PED live vaccine in vaccinated or non-vaccinated farms was evaluated by comparing the mortality rate of suckling piglets after the onset of PED. RESULTS: The challenged piglets exhibited watery diarrhea with or without vaccination. However, the clinical score of piglets born from vaccinated sows significantly improved after the 4th day of the challenge. The survival rate of piglets in the vaccinated group at the end of the experimental period was 80%, whereas in the control group was 0%. Neutralizing antibody titers in serum and milk of control sow was negative throughout the experimental period, whereas high titers were observed in the vaccinated sows. The vaccinated farms significantly reduced the mortality rate of suckling piglets after the onset of PED, compared to farms not vaccinated. CONCLUSIONS: The conventional PED live vaccine induced the lactogenic immunity to vaccinated sows and showed partial protection against the genogroup 2 virus both under the experimental and field conditions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-0940-8) contains supplementary material, which is available to authorized users.",2018 Feb 2,"['Sato, Tetsuo', 'Oroku, Kazuki', 'Ohshima, Yoshiyuki', 'Furuya, Yoshiaki', 'Sasakawa, Chihiro']",Virol J,,,False
4a80fc8045f1a85c35e038160bee95c2be0c2fd2,PMC,Efficacy of genogroup 1 based porcine epidemic diarrhea live vaccine against genogroup 2 field strain in Japan,http://dx.doi.org/10.1186/s12985-018-0940-8,PMC5797392,29394943,CC BY,"BACKGROUND: Porcine epidemic diarrhea (PED) is a lethal infectious disease in suckling piglets with symptoms including watery diarrhea caused by PED virus (PEDV). Since the late 1990’s, live vaccines based on genogroup 1 virus have been used in Japan, and a significant amount of the vaccine has been used even after new genogroups invaded in 2013. In this study, we evaluated the effect of a conventional PED live vaccine on a newly prevalent genogroup 2 field strain in experimental and field situations. METHODS: Two pregnant sows were administered twice the live vaccine before farrowing. A pregnant sow was served as a negative control. All newborn piglets were challenged with the genogroup 2 virus, and clinical signs were monitored for 7 days post challenge. PEDV-specific immune responses in serum and milk of the sows were assayed by virus neutralization assay. The efficacy of PED live vaccine in vaccinated or non-vaccinated farms was evaluated by comparing the mortality rate of suckling piglets after the onset of PED. RESULTS: The challenged piglets exhibited watery diarrhea with or without vaccination. However, the clinical score of piglets born from vaccinated sows significantly improved after the 4th day of the challenge. The survival rate of piglets in the vaccinated group at the end of the experimental period was 80%, whereas in the control group was 0%. Neutralizing antibody titers in serum and milk of control sow was negative throughout the experimental period, whereas high titers were observed in the vaccinated sows. The vaccinated farms significantly reduced the mortality rate of suckling piglets after the onset of PED, compared to farms not vaccinated. CONCLUSIONS: The conventional PED live vaccine induced the lactogenic immunity to vaccinated sows and showed partial protection against the genogroup 2 virus both under the experimental and field conditions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-0940-8) contains supplementary material, which is available to authorized users.",2018 Feb 2,"['Sato, Tetsuo', 'Oroku, Kazuki', 'Ohshima, Yoshiyuki', 'Furuya, Yoshiaki', 'Sasakawa, Chihiro']",Virol J,,,True
f41bb5faed6594d62ba991668997e97600bf0af1,PMC,A Recurrent Mutation in Anaplastic Lymphoma Kinase with Distinct Neoepitope Conformations,http://dx.doi.org/10.3389/fimmu.2018.00099,PMC5797543,29441070,CC BY,"The identification of recurrent human leukocyte antigen (HLA) neoepitopes driving T cell responses against tumors poses a significant bottleneck in the development of approaches for precision cancer therapeutics. Here, we employ a bioinformatics method, Prediction of T Cell Epitopes for Cancer Therapy, to analyze sequencing data from neuroblastoma patients and identify a recurrent anaplastic lymphoma kinase mutation (ALK R1275Q) that leads to two high affinity neoepitopes when expressed in complex with common HLA alleles. Analysis of the X-ray structures of the two peptides bound to HLA-B*15:01 reveals drastically different conformations with measurable changes in the stability of the protein complexes, while the self-epitope is excluded from binding due to steric hindrance in the MHC groove. To evaluate the range of HLA alleles that could display the ALK neoepitopes, we used structure-based Rosetta comparative modeling calculations, which accurately predict several additional high affinity interactions and compare our results with commonly used prediction tools. Subsequent determination of the X-ray structure of an HLA-A*01:01 bound neoepitope validates atomic features seen in our Rosetta models with respect to key residues relevant for MHC stability and T cell receptor recognition. Finally, MHC tetramer staining of peripheral blood mononuclear cells from HLA-matched donors shows that the two neoepitopes are recognized by CD8+ T cells. This work provides a rational approach toward high-throughput identification and further optimization of putative neoantigen/HLA targets with desired recognition features for cancer immunotherapy.",2018 Jan 30,"['Toor, Jugmohit S.', 'Rao, Arjun A.', 'McShan, Andrew C.', 'Yarmarkovich, Mark', 'Nerli, Santrupti', 'Yamaguchi, Karissa', 'Madejska, Ada A.', 'Nguyen, Son', 'Tripathi, Sarvind', 'Maris, John M.', 'Salama, Sofie R.', 'Haussler, David', 'Sgourakis, Nikolaos G.']",Front Immunol,,,False
c590a12be43ec57a2dde2a473802c5e47e354434,PMC,A Recurrent Mutation in Anaplastic Lymphoma Kinase with Distinct Neoepitope Conformations,http://dx.doi.org/10.3389/fimmu.2018.00099,PMC5797543,29441070,CC BY,"The identification of recurrent human leukocyte antigen (HLA) neoepitopes driving T cell responses against tumors poses a significant bottleneck in the development of approaches for precision cancer therapeutics. Here, we employ a bioinformatics method, Prediction of T Cell Epitopes for Cancer Therapy, to analyze sequencing data from neuroblastoma patients and identify a recurrent anaplastic lymphoma kinase mutation (ALK R1275Q) that leads to two high affinity neoepitopes when expressed in complex with common HLA alleles. Analysis of the X-ray structures of the two peptides bound to HLA-B*15:01 reveals drastically different conformations with measurable changes in the stability of the protein complexes, while the self-epitope is excluded from binding due to steric hindrance in the MHC groove. To evaluate the range of HLA alleles that could display the ALK neoepitopes, we used structure-based Rosetta comparative modeling calculations, which accurately predict several additional high affinity interactions and compare our results with commonly used prediction tools. Subsequent determination of the X-ray structure of an HLA-A*01:01 bound neoepitope validates atomic features seen in our Rosetta models with respect to key residues relevant for MHC stability and T cell receptor recognition. Finally, MHC tetramer staining of peripheral blood mononuclear cells from HLA-matched donors shows that the two neoepitopes are recognized by CD8+ T cells. This work provides a rational approach toward high-throughput identification and further optimization of putative neoantigen/HLA targets with desired recognition features for cancer immunotherapy.",2018 Jan 30,"['Toor, Jugmohit S.', 'Rao, Arjun A.', 'McShan, Andrew C.', 'Yarmarkovich, Mark', 'Nerli, Santrupti', 'Yamaguchi, Karissa', 'Madejska, Ada A.', 'Nguyen, Son', 'Tripathi, Sarvind', 'Maris, John M.', 'Salama, Sofie R.', 'Haussler, David', 'Sgourakis, Nikolaos G.']",Front Immunol,,,True
bf931c3fa287d161d951ce9545d253daaf8a14e0,PMC,Three-Dimensional Architecture and Biogenesis of Membrane Structures Associated with Plant Virus Replication,http://dx.doi.org/10.3389/fpls.2018.00057,PMC5797596,29441085,CC BY,"Positive-sense (+) RNA viruses represent the most abundant group of viruses and are dependent on the host cell machinery to replicate. One remarkable feature that occurs after (+) RNA virus entry into cells is the remodeling of host endomembranes, leading to the formation of viral replication factories. Recently, rapid progress in three-dimensional (3D) imaging technologies, such as electron tomography (ET) and focused ion beam-scanning electron microscopy (FIB-SEM), has enabled researchers to visualize the novel membrane structures induced by viruses at high resolution. These 3D imaging technologies provide new mechanistic insights into the viral infection cycle. In this review, we summarize the latest reports on the cellular remodeling that occurs during plant virus infection; in particular, we focus on studies that provide 3D architectural information on viral replication factories. We also outline the mechanisms underlying the formation of these membranous structures and discuss possible future research directions.",2018 Jan 30,"['Jin, Xuejiao', 'Cao, Xiuling', 'Wang, Xueting', 'Jiang, Jun', 'Wan, Juan', 'Laliberté, Jean-François', 'Zhang, Yongliang']",Front Plant Sci,,,True
ff7bf5c8a285587c9e39f4acacd57aee0aa77981,PMC,Non-specific Effect of Vaccines: Immediate Protection against Respiratory Syncytial Virus Infection by a Live Attenuated Influenza Vaccine,http://dx.doi.org/10.3389/fmicb.2018.00083,PMC5797773,29445364,CC BY,"The non-specific effects (NSEs) of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV) induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV). The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses. The vaccination induced an immediate release of cytokines and infiltration of leukocytes into the respiratory tract, moderating the immune perturbation caused by RSV infection. The potency of protection against RSV challenge was significantly reduced in TLR3(-/-) TLR7(-/-) mice, confirming that the TLR3/7 signaling pathways are necessary for the observed immediate and short-term protection. The results suggest that CAIVs provide short-term, non-specific protection against genetically unrelated respiratory pathogens. The additional benefits of CAIVs in mitigating acute respiratory infections for which vaccines are not yet available need to be assessed in future studies.",2018 Jan 31,"['Lee, Young J.', 'Lee, Jeong Y.', 'Jang, Yo H.', 'Seo, Sang-Uk', 'Chang, Jun', 'Seong, Baik L.']",Front Microbiol,,,True
a0c63dfdc2dba0ccca7f0026b0bedc145649d27d,PMC,Non-specific Effect of Vaccines: Immediate Protection against Respiratory Syncytial Virus Infection by a Live Attenuated Influenza Vaccine,http://dx.doi.org/10.3389/fmicb.2018.00083,PMC5797773,29445364,CC BY,"The non-specific effects (NSEs) of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV) induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV). The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses. The vaccination induced an immediate release of cytokines and infiltration of leukocytes into the respiratory tract, moderating the immune perturbation caused by RSV infection. The potency of protection against RSV challenge was significantly reduced in TLR3(-/-) TLR7(-/-) mice, confirming that the TLR3/7 signaling pathways are necessary for the observed immediate and short-term protection. The results suggest that CAIVs provide short-term, non-specific protection against genetically unrelated respiratory pathogens. The additional benefits of CAIVs in mitigating acute respiratory infections for which vaccines are not yet available need to be assessed in future studies.",2018 Jan 31,"['Lee, Young J.', 'Lee, Jeong Y.', 'Jang, Yo H.', 'Seo, Sang-Uk', 'Chang, Jun', 'Seong, Baik L.']",Front Microbiol,,,False
8525c0b448a38d6453441a36426ce4c7a28c4e18,PMC,Detection of Zika virus using reverse-transcription LAMP coupled with reverse dot blot analysis in saliva,http://dx.doi.org/10.1371/journal.pone.0192398,PMC5798782,29401479,CC BY,"In recent years, there have been increasing numbers of infectious disease outbreaks that spread rapidly to population centers resulting from global travel, population vulnerabilities, environmental factors, and ecological disasters such as floods and earthquakes. Some examples of the recent outbreaks are the Ebola epidemic in West Africa, Middle East respiratory syndrome coronavirus (MERS-Co) in the Middle East, and the Zika outbreak through the Americas. We have created a generic protocol for detection of pathogen RNA and/or DNA using loop-mediated isothermal amplification (LAMP) and reverse dot-blot for detection (RDB) and processed automatically in a microfluidic device. In particular, we describe how a microfluidic assay to detect HIV viral RNA was converted to detect Zika virus (ZIKV) RNA. We first optimized the RT-LAMP assay to detect ZIKV RNA using a benchtop isothermal amplification device. Then we implemented the assay in a microfluidic device that will allow analyzing 24 samples simultaneously and automatically from sample introduction to detection by RDB technique. Preliminary data using saliva samples spiked with ZIKV showed that our diagnostic system detects ZIKV RNA in saliva. These results will be validated in further experiments with well-characterized ZIKV human specimens of saliva. The described strategy and methodology to convert the HIV diagnostic assay and platform to a ZIKV RNA detection assay provides a model that can be readily utilized for detection of the next emerging or re-emerging infectious disease.",2018 Feb 5,"['Sabalza, Maite', 'Yasmin, Rubina', 'Barber, Cheryl A.', 'Castro, Talita', 'Malamud, Daniel', 'Kim, Beum Jun', 'Zhu, Hui', 'Montagna, Richard A.', 'Abrams, William R.']",PLoS One,,,True
d00648209ca5de4e196a97b0655de7bd181f518e,PMC,Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions,http://dx.doi.org/10.7554/eLife.31662,PMC5798934,29345620,CC BY,"Uropathogenic E. coli (UPEC), which cause urinary tract infections (UTI), utilize type 1 pili, a chaperone usher pathway (CUP) pilus, to cause UTI and colonize the gut. The pilus rod, comprised of repeating FimA subunits, provides a structural scaffold for displaying the tip adhesin, FimH. We solved the 4.2 Å resolution structure of the type 1 pilus rod using cryo-electron microscopy. Residues forming the interactive surfaces that determine the mechanical properties of the rod were maintained by selection based on a global alignment of fimA sequences. We identified mutations that did not alter pilus production in vitro but reduced the force required to unwind the rod. UPEC expressing these mutant pili were significantly attenuated in bladder infection and intestinal colonization in mice. This study elucidates an unappreciated functional role for the molecular spring-like property of type 1 pilus rods in host-pathogen interactions and carries important implications for other pilus-mediated diseases.",,"['Spaulding, Caitlin N', 'Schreiber, Henry Louis', 'Zheng, Weili', 'Dodson, Karen W', 'Hazen, Jennie E', 'Conover, Matt S', 'Wang, Fengbin', 'Svenmarker, Pontus', 'Luna-Rico, Areli', 'Francetic, Olivera', 'Andersson, Magnus', 'Hultgren, Scott', 'Egelman, Edward H']",eLife.; 7:e31662,,,True
c8d13b41dccb19715d1a0acd787330a481b9010e,PMC,Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions,http://dx.doi.org/10.7554/eLife.31662,PMC5798934,29345620,CC BY,"Uropathogenic E. coli (UPEC), which cause urinary tract infections (UTI), utilize type 1 pili, a chaperone usher pathway (CUP) pilus, to cause UTI and colonize the gut. The pilus rod, comprised of repeating FimA subunits, provides a structural scaffold for displaying the tip adhesin, FimH. We solved the 4.2 Å resolution structure of the type 1 pilus rod using cryo-electron microscopy. Residues forming the interactive surfaces that determine the mechanical properties of the rod were maintained by selection based on a global alignment of fimA sequences. We identified mutations that did not alter pilus production in vitro but reduced the force required to unwind the rod. UPEC expressing these mutant pili were significantly attenuated in bladder infection and intestinal colonization in mice. This study elucidates an unappreciated functional role for the molecular spring-like property of type 1 pilus rods in host-pathogen interactions and carries important implications for other pilus-mediated diseases.",,"['Spaulding, Caitlin N', 'Schreiber, Henry Louis', 'Zheng, Weili', 'Dodson, Karen W', 'Hazen, Jennie E', 'Conover, Matt S', 'Wang, Fengbin', 'Svenmarker, Pontus', 'Luna-Rico, Areli', 'Francetic, Olivera', 'Andersson, Magnus', 'Hultgren, Scott', 'Egelman, Edward H']",eLife.; 7:e31662,,,False
a8dc7f137a340a631699a817a26b4b4d26136e7b,PMC,Insights into the Structural Basis of Antibody Affinity Maturation from Next-Generation Sequencing,http://dx.doi.org/10.3389/fimmu.2018.00117,PMC5799246,29449843,CC BY,"Affinity maturation is the process whereby the immune system generates antibodies of higher affinities during a response to antigen. It is unique in being the only evolutionary mechanism known to operate on a molecule in an organism’s own body. Deciphering the structural mechanisms through which somatic mutations in antibody genes increase affinity is critical to understanding the evolution of immune repertoires. Next-generation sequencing (NGS) has allowed the reconstruction of antibody clonal lineages in response to viral pathogens, such as HIV-1, which was not possible in earlier studies of affinity maturation. Crystal structures of antibodies from these lineages bound to their target antigens have revealed, at the atomic level, how antibodies evolve to penetrate the glycan shield of envelope glycoproteins, and how viruses in turn evolve to escape neutralization. Collectively, structural studies of affinity maturation have shown that increased antibody affinity can arise from any one or any combination of multiple diverse mechanisms, including improved shape complementarity at the interface with antigen, increased buried surface area upon complex formation, additional interfacial polar or hydrophobic interactions, and preorganization or rigidification of the antigen-binding site.",2018 Feb 1,"['Mishra, Arjun K.', 'Mariuzza, Roy A.']",Front Immunol,,,True
300684bd7c47e1f3e8373cb250c6ad82a359955d,PMC,Molecular analysis of carnivore Protoparvovirus detected in white blood cells of naturally infected cats,http://dx.doi.org/10.1186/s12917-018-1356-9,PMC5799907,29402272,CC BY,"BACKGROUND: Cats are susceptible to feline panleukopenia virus (FPV) and canine parvovirus (CPV) variants 2a, 2b and 2c. Detection of FPV and CPV variants in apparently healthy cats and their persistence in white blood cells (WBC) and other tissues when neutralising antibodies are simultaneously present, suggest that parvovirus may persist long-term in the tissues of cats post-infection without causing clinical signs. The aim of this study was to screen a population of 54 cats from Sardinia (Italy) for the presence of both FPV and CPV DNA within buffy coat samples using polymerase chain reaction (PCR). The DNA viral load, genetic diversity, phylogeny and antibody titres against parvoviruses were investigated in the positive cats. RESULTS: Carnivore protoparvovirus 1 DNA was detected in nine cats (16.7%). Viral DNA was reassembled to FPV in four cats and to CPV (CPV-2b and 2c) in four cats; one subject showed an unusually high genetic complexity with mixed infection involving FPV and CPV-2c. Antibodies against parvovirus were detected in all subjects which tested positive to DNA parvoviruses. CONCLUSIONS: The identification of FPV and CPV DNA in the WBC of asymptomatic cats, despite the presence of specific antibodies against parvoviruses, and the high genetic heterogeneity detected in one sample, confirmed the relevant epidemiological role of cats in parvovirus infection.",2018 Feb 5,"['Balboni, Andrea', 'Bassi, Francesca', 'De Arcangeli, Stefano', 'Zobba, Rosanna', 'Dedola, Carla', 'Alberti, Alberto', 'Battilani, Mara']",BMC Vet Res,,,True
514e24bfc28e0b5cf4b111d94604e7aa983500c9,PMC,MERS-CoV 4b protein interferes with the NF-κB-dependent innate immune response during infection,http://dx.doi.org/10.1371/journal.ppat.1006838,PMC5800688,29370303,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel human coronavirus that emerged in 2012, causing severe pneumonia and acute respiratory distress syndrome (ARDS), with a case fatality rate of ~36%. When expressed in isolation, CoV accessory proteins have been shown to interfere with innate antiviral signaling pathways. However, there is limited information on the specific contribution of MERS-CoV accessory protein 4b to the repression of the innate antiviral response in the context of infection. We found that MERS-CoV 4b was required to prevent a robust NF-κB dependent response during infection. In wild-type virus infected cells, 4b localized to the nucleus, while NF-κB was retained in the cytoplasm. In contrast, in the absence of 4b or in the presence of cytoplasmic 4b mutants lacking a nuclear localization signal (NLS), NF-κB was translocated to the nucleus leading to the expression of pro-inflammatory cytokines. This indicates that NF-κB repression required the nuclear import of 4b mediated by a specific NLS. Interestingly, we also found that both in isolation and during infection, 4b interacted with α-karyopherin proteins in an NLS-dependent manner. In particular, 4b had a strong preference for binding karyopherin-α4 (KPNA4), which is known to translocate the NF-κB protein complex into the nucleus. Binding of 4b to KPNA4 during infection inhibited its interaction with NF-κB-p65 subunit. Thereby we propose a model where 4b outcompetes NF-κB for KPNA4 binding and translocation into the nucleus as a mechanism of interference with the NF-κB-mediated innate immune response.",2018 Jan 25,"['Canton, Javier', 'Fehr, Anthony R.', 'Fernandez-Delgado, Raúl', 'Gutierrez-Alvarez, Francisco J.', 'Sanchez-Aparicio, Maria T.', 'García-Sastre, Adolfo', 'Perlman, Stanley', 'Enjuanes, Luis', 'Sola, Isabel']",PLoS Pathog,,,True
6e0b5bbe1af91b80c9ac2fa22fea4d845c6230c8,PMC,Control of Infectious Diseases in the Era of European Clinical Microbiology Laboratory Consolidation: New Challenges and Opportunities for the Patient and for Public Health Surveillance,http://dx.doi.org/10.3389/fmed.2018.00015,PMC5801420,29457001,CC BY,"Many new innovative diagnostic approaches have been made available during the last 10 years with major impact on patient care and public health surveillance. In parallel, to enhance the cost-effectiveness of the clinical microbiology laboratories (CMLs), European laboratory professionals have streamlined their organization leading to amalgamation of activities and restructuring of their professional relationships with clinicians and public health specialists. Through this consolidation process, an operational model has emerged that combines large centralized clinical laboratories performing most tests on one high-throughput analytical platform connected to several distal laboratories dealing locally with urgent analyses at near point of care. The centralization of diagnostic services over a large geographical region has given rise to the concept of regional-scale “microbiology laboratories network.” Although the volume-driven cost savings associated with such laboratory networks seem self-evident, the consequence(s) for the quality of patient care and infectious disease surveillance and control remain less obvious. In this article, we describe the range of opportunities that the changing landscape of CMLs in Europe can contribute toward improving the quality of patient care but also the early detection and enhanced surveillance of public health threats caused by infectious diseases. The success of this transformation of health services is reliant on the appropriate preparation in terms of staff, skills, and processes that would be inclusive of stakeholders. In addition, rigorous metrics are needed to set out more concrete laboratory service performance objectives and assess the expected benefits to society in terms of saving lives and preventing diseases.",2018 Feb 2,"['Vandenberg, Olivier', 'Kozlakidis, Zisis', 'Schrenzel, Jacques', 'Struelens, Marc Jean', 'Breuer, Judith']",Front Med (Lausanne),,,True
b880cad36f03039d17617ae8be7e885caa54b7fa,PMC,Chimeric Pneumoviridae fusion proteins as immunogens to induce cross‐neutralizing antibody responses,http://dx.doi.org/10.15252/emmm.201708078,PMC5801496,29217660,CC BY,"Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV), two members of the Pneumoviridae family, account for the majority of severe lower respiratory tract infections worldwide in very young children. They are also a frequent cause of morbidity and mortality in the elderly and immunocompromised adults. High levels of neutralizing antibodies, mostly directed against the viral fusion (F) glycoprotein, correlate with protection against either hRSV or hMPV. However, no cross‐neutralization is observed in polyclonal antibody responses raised after virus infection or immunization with purified F proteins. Based on crystal structures of hRSV F and hMPV F, we designed chimeric F proteins in which certain residues of well‐characterized antigenic sites were swapped between the two antigens. The antigenic changes were monitored by ELISA with virus‐specific monoclonal antibodies. Inoculation of mice with these chimeras induced polyclonal cross‐neutralizing antibody responses, and mice were protected against challenge with the virus used for grafting of the heterologous antigenic site. These results provide a proof of principle for chimeric fusion proteins as single immunogens that can induce cross‐neutralizing antibody and protective responses against more than one human pneumovirus.",2018 Feb 7,"['Olmedillas, Eduardo', 'Cano, Olga', 'Martínez, Isidoro', 'Luque, Daniel', 'Terrón, María C', 'McLellan, Jason S', 'Melero, José A', 'Más, Vicente']",EMBO Mol Med,,,True
1dbd36d657cbabb92b2c57f2db8d294837655e74,PMC,Chimeric Pneumoviridae fusion proteins as immunogens to induce cross‐neutralizing antibody responses,http://dx.doi.org/10.15252/emmm.201708078,PMC5801496,29217660,CC BY,"Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV), two members of the Pneumoviridae family, account for the majority of severe lower respiratory tract infections worldwide in very young children. They are also a frequent cause of morbidity and mortality in the elderly and immunocompromised adults. High levels of neutralizing antibodies, mostly directed against the viral fusion (F) glycoprotein, correlate with protection against either hRSV or hMPV. However, no cross‐neutralization is observed in polyclonal antibody responses raised after virus infection or immunization with purified F proteins. Based on crystal structures of hRSV F and hMPV F, we designed chimeric F proteins in which certain residues of well‐characterized antigenic sites were swapped between the two antigens. The antigenic changes were monitored by ELISA with virus‐specific monoclonal antibodies. Inoculation of mice with these chimeras induced polyclonal cross‐neutralizing antibody responses, and mice were protected against challenge with the virus used for grafting of the heterologous antigenic site. These results provide a proof of principle for chimeric fusion proteins as single immunogens that can induce cross‐neutralizing antibody and protective responses against more than one human pneumovirus.",2018 Feb 7,"['Olmedillas, Eduardo', 'Cano, Olga', 'Martínez, Isidoro', 'Luque, Daniel', 'Terrón, María C', 'McLellan, Jason S', 'Melero, José A', 'Más, Vicente']",EMBO Mol Med,,,False
df0310a74d62210e31be9fbe879085499825b14d,PMC,Chimeric Pneumoviridae fusion proteins as immunogens to induce cross‐neutralizing antibody responses,http://dx.doi.org/10.15252/emmm.201708078,PMC5801496,29217660,CC BY,"Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV), two members of the Pneumoviridae family, account for the majority of severe lower respiratory tract infections worldwide in very young children. They are also a frequent cause of morbidity and mortality in the elderly and immunocompromised adults. High levels of neutralizing antibodies, mostly directed against the viral fusion (F) glycoprotein, correlate with protection against either hRSV or hMPV. However, no cross‐neutralization is observed in polyclonal antibody responses raised after virus infection or immunization with purified F proteins. Based on crystal structures of hRSV F and hMPV F, we designed chimeric F proteins in which certain residues of well‐characterized antigenic sites were swapped between the two antigens. The antigenic changes were monitored by ELISA with virus‐specific monoclonal antibodies. Inoculation of mice with these chimeras induced polyclonal cross‐neutralizing antibody responses, and mice were protected against challenge with the virus used for grafting of the heterologous antigenic site. These results provide a proof of principle for chimeric fusion proteins as single immunogens that can induce cross‐neutralizing antibody and protective responses against more than one human pneumovirus.",2018 Feb 7,"['Olmedillas, Eduardo', 'Cano, Olga', 'Martínez, Isidoro', 'Luque, Daniel', 'Terrón, María C', 'McLellan, Jason S', 'Melero, José A', 'Más, Vicente']",EMBO Mol Med,,,True
32d5b5c7b38c1dd14b316de97bce86e5ab252f91,PMC,Development and characterization of serotype-specific monoclonal antibodies against the dengue virus-4 (DENV-4) non-structural protein (NS1),http://dx.doi.org/10.1186/s12985-018-0925-7,PMC5801815,29409531,CC BY,"BACKGROUND: Dengue, caused by one of the four serologically distinct dengue viruses (DENV-1 to − 4), is a mosquito-borne disease of serious global health significance. Reliable and cost-effective diagnostic tests, along with effective vaccines and vector-control strategies, are highly required to reduce dengue morbidity and mortality. Evaluation studies revealed that many commercially available NS1 antigen (Ag) tests have limited sensitivity to DENV-4 serotype compared to the other three serotypes. These studies indicated the need for development of new NS1 Ag detection test with improved sensitivity to DENV-4. An NS1 capture enzyme linked immunoassay (ELISA) specific to DENV-4 may improve the detection of DENV-4 cases worldwide. In addition, a serotype-specific NS1 Ag test identifies both DENV and the infecting serotype. METHODS: In this study, we used a small-ubiquitin-like modifier (SUMO*) cloning vector to express a SUMO*-DENV-4 rNS1 fusion protein to develop NS1 DENV-4 specific monoclonal antibodies (MAbs). These newly developed MAbs were then optimized for use in an anti-NS1 DENV-4 capture ELISA. The serotype specificity and sensitivity of this ELISA was evaluated using (i) supernatants from DENV (1–4)-infected Vero cell cultures, (ii) rNS1s from all the four DENV (1–4) and, (iii) rNS1s of related flaviviruses (yellow fever virus; YFV and West Nile virus; WNV). RESULTS: From the evaluation studies of the newly developed MAbs, we identified three DENV-4 specific anti-NS1 MAbs: 3H7A9, 8A6F2 and 6D4B10. Two of these MAbs were optimal for use in a DENV-4 serotype-specific NS1 capture ELISA: MAb 8A6F2 as the capture antibody and 6D4B10 as a detection antibody. CONCLUSION: This ELISA was sensitive and specific to DENV-4 with no cross-reactivity to other three DENV (1–3) serotypes and other heterologous flaviviruses. Taken together these data indicated that our MAbs are useful reagents for the development of DENV-4 immunodiagnostic tests. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi: 10.1186/s12985-018-0925-7) contains supplementary material, which is available to authorized users.",2018 Feb 6,"['Gelanew, Tesfaye', 'Hunsperger, Elizabeth']",Virol J,,,True
5f81496a02673e6967f71dfbc8d4112a29d3d1b8,PMC,Broad-spectrum neutralization of avian influenza viruses by sialylated human milk oligosaccharides: in vivo assessment of 3′-sialyllactose against H9N2 in chickens,http://dx.doi.org/10.1038/s41598-018-20955-4,PMC5803236,29416087,CC BY,"Two sialylated human milk oligosaccharides (SHMOs) 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL) were accessed for their possible antiviral activity against six different subtypes of thirteen avian influenza (AI) viruses in vitro. 3′-SL exhibited promising antiviral activity against almost all subtypes of tested AI viruses in hemagglutination inhibition assay, whereas 6′-SL showed activity against few selected H1N1, H1N2, and H3N2 subtype strains. 3′-SL has minimum inhibitory concentration values of 15.62 mM or less in more than half of the viruses examined. 3′-SL also showed effective inactivation of H9N2 Korea isolate (A/Chicken/Korea/MS96/1996) at 12.5 mM concentration in Madin Darby Canine Kidney (MDCK) cell line. Thus, 3′-SL was further studied for in vivo study against H9N2 virus in pathogen free chicken experiment models. In vivo study exhibited improved clinical symptoms on H9N2 infected chickens when treated with 3′-SL. Moreover, treating chickens with 3′-SL resulted in complete elimination of H9N2 viruses within 24 h of virus infection (0.8 HAU of H9N2). Indirect ELISA assay confirmed complete wash-out of H9N2 viruses from the colon after neutralization by 3′-SL without entering the blood stream. These in vivo results open up possible applications of 3′-SL for the prevention of AI virus infections in birds by a simple cleansing mechanism.",2018 Feb 7,"['Pandey, Ramesh Prasad', 'Kim, Dae Hee', 'Woo, Jinsuk', 'Song, Jaeyoung', 'Jang, Sang Ho', 'Kim, Joon Bae', 'Cheong, Kwang Myun', 'Oh, Jin Sik', 'Sohng, Jae Kyung']",Sci Rep,,,True
6275144a4a4a08d1c72f3c52109ac757c72e6424,PMC,What incentives increase data sharing in health and medical research? A systematic review,http://dx.doi.org/10.1186/s41073-017-0028-9,PMC5803640,29451561,CC BY,"BACKGROUND: The foundation of health and medical research is data. Data sharing facilitates the progress of research and strengthens science. Data sharing in research is widely discussed in the literature; however, there are seemingly no evidence-based incentives that promote data sharing. METHODS: A systematic review (registration: 10.17605/OSF.IO/6PZ5E) of the health and medical research literature was used to uncover any evidence-based incentives, with pre- and post-empirical data that examined data sharing rates. We were also interested in quantifying and classifying the number of opinion pieces on the importance of incentives, the number observational studies that analysed data sharing rates and practices, and strategies aimed at increasing data sharing rates. RESULTS: Only one incentive (using open data badges) has been tested in health and medical research that examined data sharing rates. The number of opinion pieces (n = 85) out-weighed the number of article-testing strategies (n = 76), and the number of observational studies exceeded them both (n = 106). CONCLUSIONS: Given that data is the foundation of evidence-based health and medical research, it is paradoxical that there is only one evidence-based incentive to promote data sharing. More well-designed studies are needed in order to increase the currently low rates of data sharing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s41073-017-0028-9) contains supplementary material, which is available to authorized users.",2017 May 5,"['Rowhani-Farid, Anisa', 'Allen, Michelle', 'Barnett, Adrian G.']",Res Integr Peer Rev,,,True
e911d262fbf4b651d8b2f2acb97c71e157a4d4cd,PMC,Human cytomegalovirus UL23 inhibits transcription of interferon-γ stimulated genes and blocks antiviral interferon-γ responses by interacting with human N-myc interactor protein,http://dx.doi.org/10.1371/journal.ppat.1006867,PMC5805366,29377960,CC BY,"Interferon-γ (IFN-γ) represents one of the most important innate immunity responses in a host to combat infections of many human viruses including human herpesviruses. Human N-myc interactor (Nmi) protein, which has been shown to interact with signal transducer and activator of transcription (STAT) proteins including STAT1, is important for the activation of IFN-γ induced STAT1-dependent transcription of many genes responsible for IFN-γ immune responses. However, no proteins encoded by herpesviruses have been reported to interact with Nmi and inhibit Nmi-mediated activation of IFN-γ immune responses to achieve immune evasion from IFN-γ responses. In this study, we show strong evidence that the UL23 protein of human cytomegalovirus (HCMV), a human herpesvirus, specifically interacts with Nmi. This interaction was identified through a yeast two-hybrid screen and co-immunoprecipitation in human cells. We observed that Nmi, when bound to UL23, was not associated with STAT1, suggesting that UL23 binding of Nmi disrupts the interaction of Nmi with STAT1. In cells overexpressing UL23, we observed (a) significantly reduced levels of Nmi and STAT1 in the nuclei, the sites where these proteins act to induce transcription of IFN-γ stimulated genes, and (b) decreased levels of the induction of the transcription of IFN-γ stimulated genes. UL23-deficient HCMV mutants induced higher transcription of IFN-γ stimulated genes and exhibited lower titers than parental and control revertant viruses expressing functional UL23 in IFN-γ treated cells. Thus, UL23 appears to interact directly with Nmi and inhibit nuclear translocation of Nmi and its associated protein STAT1, leading to a decrease of IFN-γ induced responses and an increase of viral resistance to IFN-γ. Our results further highlight the roles of UL23-Nmi interactions in facilitating viral immune escape from IFN-γ responses and enhancing viral resistance to IFN antiviral effects.",2018 Jan 29,"['Feng, Linyuan', 'Sheng, Jingxue', 'Vu, Gia-Phong', 'Liu, Yujun', 'Foo, Chingman', 'Wu, Songbin', 'Trang, Phong', 'Paliza-Carre, Marco', 'Ran, Yanhong', 'Yang, Xiaoping', 'Sun, Xu', 'Deng, Zemin', 'Zhou, Tianhong', 'Lu, Sangwei', 'Li, Hongjian', 'Liu, Fenyong']",PLoS Pathog,,,True
84f37c15472f84a4f103fbd8f4ab33a7fc9e66ed,PMC,Human cytomegalovirus UL23 inhibits transcription of interferon-γ stimulated genes and blocks antiviral interferon-γ responses by interacting with human N-myc interactor protein,http://dx.doi.org/10.1371/journal.ppat.1006867,PMC5805366,29377960,CC BY,"Interferon-γ (IFN-γ) represents one of the most important innate immunity responses in a host to combat infections of many human viruses including human herpesviruses. Human N-myc interactor (Nmi) protein, which has been shown to interact with signal transducer and activator of transcription (STAT) proteins including STAT1, is important for the activation of IFN-γ induced STAT1-dependent transcription of many genes responsible for IFN-γ immune responses. However, no proteins encoded by herpesviruses have been reported to interact with Nmi and inhibit Nmi-mediated activation of IFN-γ immune responses to achieve immune evasion from IFN-γ responses. In this study, we show strong evidence that the UL23 protein of human cytomegalovirus (HCMV), a human herpesvirus, specifically interacts with Nmi. This interaction was identified through a yeast two-hybrid screen and co-immunoprecipitation in human cells. We observed that Nmi, when bound to UL23, was not associated with STAT1, suggesting that UL23 binding of Nmi disrupts the interaction of Nmi with STAT1. In cells overexpressing UL23, we observed (a) significantly reduced levels of Nmi and STAT1 in the nuclei, the sites where these proteins act to induce transcription of IFN-γ stimulated genes, and (b) decreased levels of the induction of the transcription of IFN-γ stimulated genes. UL23-deficient HCMV mutants induced higher transcription of IFN-γ stimulated genes and exhibited lower titers than parental and control revertant viruses expressing functional UL23 in IFN-γ treated cells. Thus, UL23 appears to interact directly with Nmi and inhibit nuclear translocation of Nmi and its associated protein STAT1, leading to a decrease of IFN-γ induced responses and an increase of viral resistance to IFN-γ. Our results further highlight the roles of UL23-Nmi interactions in facilitating viral immune escape from IFN-γ responses and enhancing viral resistance to IFN antiviral effects.",2018 Jan 29,"['Feng, Linyuan', 'Sheng, Jingxue', 'Vu, Gia-Phong', 'Liu, Yujun', 'Foo, Chingman', 'Wu, Songbin', 'Trang, Phong', 'Paliza-Carre, Marco', 'Ran, Yanhong', 'Yang, Xiaoping', 'Sun, Xu', 'Deng, Zemin', 'Zhou, Tianhong', 'Lu, Sangwei', 'Li, Hongjian', 'Liu, Fenyong']",PLoS Pathog,,,False
510df094b943c60422ef861ed91abade4a4ade4d,PMC,Human cytomegalovirus UL23 inhibits transcription of interferon-γ stimulated genes and blocks antiviral interferon-γ responses by interacting with human N-myc interactor protein,http://dx.doi.org/10.1371/journal.ppat.1006867,PMC5805366,29377960,CC BY,"Interferon-γ (IFN-γ) represents one of the most important innate immunity responses in a host to combat infections of many human viruses including human herpesviruses. Human N-myc interactor (Nmi) protein, which has been shown to interact with signal transducer and activator of transcription (STAT) proteins including STAT1, is important for the activation of IFN-γ induced STAT1-dependent transcription of many genes responsible for IFN-γ immune responses. However, no proteins encoded by herpesviruses have been reported to interact with Nmi and inhibit Nmi-mediated activation of IFN-γ immune responses to achieve immune evasion from IFN-γ responses. In this study, we show strong evidence that the UL23 protein of human cytomegalovirus (HCMV), a human herpesvirus, specifically interacts with Nmi. This interaction was identified through a yeast two-hybrid screen and co-immunoprecipitation in human cells. We observed that Nmi, when bound to UL23, was not associated with STAT1, suggesting that UL23 binding of Nmi disrupts the interaction of Nmi with STAT1. In cells overexpressing UL23, we observed (a) significantly reduced levels of Nmi and STAT1 in the nuclei, the sites where these proteins act to induce transcription of IFN-γ stimulated genes, and (b) decreased levels of the induction of the transcription of IFN-γ stimulated genes. UL23-deficient HCMV mutants induced higher transcription of IFN-γ stimulated genes and exhibited lower titers than parental and control revertant viruses expressing functional UL23 in IFN-γ treated cells. Thus, UL23 appears to interact directly with Nmi and inhibit nuclear translocation of Nmi and its associated protein STAT1, leading to a decrease of IFN-γ induced responses and an increase of viral resistance to IFN-γ. Our results further highlight the roles of UL23-Nmi interactions in facilitating viral immune escape from IFN-γ responses and enhancing viral resistance to IFN antiviral effects.",2018 Jan 29,"['Feng, Linyuan', 'Sheng, Jingxue', 'Vu, Gia-Phong', 'Liu, Yujun', 'Foo, Chingman', 'Wu, Songbin', 'Trang, Phong', 'Paliza-Carre, Marco', 'Ran, Yanhong', 'Yang, Xiaoping', 'Sun, Xu', 'Deng, Zemin', 'Zhou, Tianhong', 'Lu, Sangwei', 'Li, Hongjian', 'Liu, Fenyong']",PLoS Pathog,,,False
a4c0d3619ba273adce8a9d0df51eca6adaaf2f23,PMC,"Complete Genome Sequence of a Recombinant Porcine Epidemic Diarrhea Virus Strain, CH/JXJA/2017, Isolated in Jiangxi, China, in 2017",http://dx.doi.org/10.1128/genomeA.01590-17,PMC5805890,29439052,CC BY,"The full-length genome sequence of a variant of porcine epidemic diarrhea virus (PEDV), that of strain CH/JXJA/2017, was highly homologous to CH/ZMDZY/11, a highly virulent Chinese PEDV strain. CH/JXJA/2017 had a distant relationship with the attenuated CV777 vaccine strain, but the insertion sites of the S1 gene were similar to those of the recombinant strain of CH/ZMDZY/11.",2018 Feb 8,"['Li, Kai', 'Song, Deping', 'Zhang, Fanfan', 'Gong, Wang', 'Guo, Nannan', 'Li, Anqi', 'Zhou, Xingrong', 'Huang, Dongyan', 'Ye, Yu', 'Tang, Yuxin']",Genome Announc,,,True
3a1c74872d4e0aa20076dc1f3970d9ff42991847,PMC,Temporal variation of human encounters and the number of locations in which they occur: a longitudinal study of Hong Kong residents,http://dx.doi.org/10.1098/rsif.2017.0838,PMC5805989,29367241,CC BY,"Patterns of social contact between individuals are important for the transmission of many pathogens and shaping patterns of immunity at the population scale. To refine our understanding of how human social behaviour may change over time, we conducted a longitudinal study of Hong Kong residents. We recorded the social contact patterns for 1450 individuals, up to four times each between May 2012 and September 2013. We found individuals made contact with an average of 12.5 people within 2.9 geographical locations, and spent an average estimated total duration of 9.1 h in contact with others during a day. Distributions of the number of contacts and locations in which contacts were made were not significantly different between study waves. Encounters were assortative by age, and the age mixing pattern was broadly consistent across study waves. Fitting regression models, we examined the association of contact rates (number of contacts, total duration of contact, number of locations) with covariates and calculated the inter- and intra-participant variation in contact rates. Participant age was significantly associated with the number of contacts made, the total duration of contact and the number of locations in which contact occurred, with children and parental-age adults having the highest rates of contact. The number of contacts and contact duration increased with the number of contact locations. Intra-individual variation in contact rate was consistently greater than inter-individual variation. Despite substantial individual-level variation, remarkable consistency was observed in contact mixing at the population scale. This suggests that aggregate measures of mixing behaviour derived from cross-sectional information may be appropriate for population-scale modelling purposes, and that if more detailed models of social interactions are required for improved public health modelling, further studies are needed to understand the social processes driving intra-individual variation.",2018 Jan 24,"['Kwok, Kin On', 'Cowling, Ben', 'Wei, Vivian', 'Riley, Steven', 'Read, Jonathan M.']",J R Soc Interface,,,True
059b9cccab6fd5bf12b180379b9d5f8768a0f4a0,PMC,Temporal variation of human encounters and the number of locations in which they occur: a longitudinal study of Hong Kong residents,http://dx.doi.org/10.1098/rsif.2017.0838,PMC5805989,29367241,CC BY,"Patterns of social contact between individuals are important for the transmission of many pathogens and shaping patterns of immunity at the population scale. To refine our understanding of how human social behaviour may change over time, we conducted a longitudinal study of Hong Kong residents. We recorded the social contact patterns for 1450 individuals, up to four times each between May 2012 and September 2013. We found individuals made contact with an average of 12.5 people within 2.9 geographical locations, and spent an average estimated total duration of 9.1 h in contact with others during a day. Distributions of the number of contacts and locations in which contacts were made were not significantly different between study waves. Encounters were assortative by age, and the age mixing pattern was broadly consistent across study waves. Fitting regression models, we examined the association of contact rates (number of contacts, total duration of contact, number of locations) with covariates and calculated the inter- and intra-participant variation in contact rates. Participant age was significantly associated with the number of contacts made, the total duration of contact and the number of locations in which contact occurred, with children and parental-age adults having the highest rates of contact. The number of contacts and contact duration increased with the number of contact locations. Intra-individual variation in contact rate was consistently greater than inter-individual variation. Despite substantial individual-level variation, remarkable consistency was observed in contact mixing at the population scale. This suggests that aggregate measures of mixing behaviour derived from cross-sectional information may be appropriate for population-scale modelling purposes, and that if more detailed models of social interactions are required for improved public health modelling, further studies are needed to understand the social processes driving intra-individual variation.",2018 Jan 24,"['Kwok, Kin On', 'Cowling, Ben', 'Wei, Vivian', 'Riley, Steven', 'Read, Jonathan M.']",J R Soc Interface,,,False
76f88935e279c736683360a22e61dbe41cc18661,PMC,"Comparison of the prevalence of respiratory viruses in patients with acute respiratory infections at different hospital settings in North China, 2012–2015",http://dx.doi.org/10.1186/s12879-018-2982-3,PMC5806372,29422011,CC BY,"BACKGROUND: Acute respiratory infections (ARIs) are a great public health challenge globally. The prevalence of respiratory viruses in patients with ARIs attending at different hospital settings is fully undetermined. METHODS: Laboratory-based surveillance for ARIs was conducted at inpatient and outpatient settings of 11 hospitals in North China. The first 2–5 patients with ARIs were recruited in each hospital weekly from 2012 through 2015. The presence of respiratory viruses was screened by PCR assays. The prevalence of respiratory viruses was determined and compared between patients at different hospital settings. RESULTS: A total of 3487 hospitalized cases and 6437 outpatients/Emergency Department (ED) patients were enrolled. The most commonly detected viruses in the hospitalized cases were respiratory syncytial virus (RSV, 33.3%) in children less than two years old, adenoviruses (13.0%) in patients 15–34 years old, and influenza viruses (IFVs, 9.6%) in patients ≥65 years. IFVs were the most common virus in outpatient/ED patients across all age groups (22.7%). After controlling for the confounders caused by other viruses and covariates, adenoviruses (adjusted odds ratio [aOR]: 3.97, 99% confidence interval [99% CI]: 2.19–7.20) and RSV (aOR: 2.04, 99% CI: 1.34–3.11) were independently associated with increased hospitalization in children, as well as adenoviruses in adults (aOR: 2.14, 99% CI: 1.19–3.85). Additionally, co-infection of RSV with IFVs was associated with increased hospitalization in children (aOR: 12.20, 99% CI: 2.65–56.18). CONCLUSIONS: A substantial proportion of ARIs was associated with respiratory viruses in North China. RSV, adenoviruses, and co-infection of RSV and IFVs were more frequent in hospitalized children (or adenoviruses in adults), which might predict the severity of ARIs. Attending clinicians should be more vigilant of these infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-2982-3) contains supplementary material, which is available to authorized users.",2018 Feb 8,"['Yu, Jianxing', 'Xie, Zhengde', 'Zhang, Tiegang', 'Lu, Yanqin', 'Fan, Hongwei', 'Yang, Donghong', 'Bénet, Thomas', 'Vanhems, Philippe', 'Shen, Kunling', 'Huang, Fang', 'Han, Jinxiang', 'Li, Taisheng', 'Gao, Zhancheng', 'Ren, Lili', 'Wang, Jianwei']",BMC Infect Dis,,,True
1f972484a578ead6c95a1dfff150894e935cad9d,PMC,Far-UVC light: A new tool to control the spread of airborne-mediated microbial diseases,http://dx.doi.org/10.1038/s41598-018-21058-w,PMC5807439,29426899,CC BY,"Airborne-mediated microbial diseases such as influenza and tuberculosis represent major public health challenges. A direct approach to prevent airborne transmission is inactivation of airborne pathogens, and the airborne antimicrobial potential of UVC ultraviolet light has long been established; however, its widespread use in public settings is limited because conventional UVC light sources are both carcinogenic and cataractogenic. By contrast, we have previously shown that far-UVC light (207–222 nm) efficiently inactivates bacteria without harm to exposed mammalian skin. This is because, due to its strong absorbance in biological materials, far-UVC light cannot penetrate even the outer (non living) layers of human skin or eye; however, because bacteria and viruses are of micrometer or smaller dimensions, far-UVC can penetrate and inactivate them. We show for the first time that far-UVC efficiently inactivates airborne aerosolized viruses, with a very low dose of 2 mJ/cm(2) of 222-nm light inactivating >95% of aerosolized H1N1 influenza virus. Continuous very low dose-rate far-UVC light in indoor public locations is a promising, safe and inexpensive tool to reduce the spread of airborne-mediated microbial diseases.",2018 Feb 9,"['Welch, David', 'Buonanno, Manuela', 'Grilj, Veljko', 'Shuryak, Igor', 'Crickmore, Connor', 'Bigelow, Alan W.', 'Randers-Pehrson, Gerhard', 'Johnson, Gary W.', 'Brenner, David J.']",Sci Rep,,,True
2aee8b6b24664409e75a87620820ce17b88c5dc0,PMC,Crystal structures of a bacterial dipeptidyl peptidase IV reveal a novel substrate recognition mechanism distinct from that of mammalian orthologues,http://dx.doi.org/10.1038/s41598-018-21056-y,PMC5807507,29426867,CC BY,"Dipeptidyl peptidase IV (DPP IV, DPP4, or DAP IV) preferentially cleaves substrate peptides with Pro or Ala at the P1 position. The substrate recognition mechanism has been fully elucidated for mammalian DPP IV by crystal structure analyses but not for bacterial orthologues. Here, we report the crystal structures of a bacterial DPP IV (PmDAP IV) in its free form and in complexes with two kinds of dipeptides as well as with a non-peptidyl inhibitor at 1.90 to 2.47 Å resolution. Acyl-enzyme intermediates were observed for the dipeptide complexes of PmDAP IV, whereas tetrahedral intermediates were reported for the oligopeptide complexes of mammalian DPP IVs. This variation reflects the different structural environments of the active site Arg residues, which are involved in the recognition of a substrate carbonyl group, of mammalian and bacterial enzymes. A phylogenetic analysis revealed that PmDAP IV is a closer relative of dipeptidyl peptidases 8 and 9 (DPP8 and DPP9, DPP IV-family enzymes) than DPP IV. These results provide new insights into the substrate recognition mechanism of bacterial DAP IVs and may assist in the development of selective inhibitors for DAP IVs from pathogenic asaccharolytic bacteria, which utilise proteins or peptides as an energy source.",2018 Feb 9,"['Roppongi, Saori', 'Suzuki, Yoshiyuki', 'Tateoka, Chika', 'Fujimoto, Mayu', 'Morisawa, Saori', 'Iizuka, Ippei', 'Nakamura, Akihiro', 'Honma, Nobuyuki', 'Shida, Yosuke', 'Ogasawara, Wataru', 'Tanaka, Nobutada', 'Sakamoto, Yasumitsu', 'Nonaka, Takamasa']",Sci Rep,,,False
2106f8105f3cb30bf479fdcb6d78e4891a204080,PMC,Crystal structures of a bacterial dipeptidyl peptidase IV reveal a novel substrate recognition mechanism distinct from that of mammalian orthologues,http://dx.doi.org/10.1038/s41598-018-21056-y,PMC5807507,29426867,CC BY,"Dipeptidyl peptidase IV (DPP IV, DPP4, or DAP IV) preferentially cleaves substrate peptides with Pro or Ala at the P1 position. The substrate recognition mechanism has been fully elucidated for mammalian DPP IV by crystal structure analyses but not for bacterial orthologues. Here, we report the crystal structures of a bacterial DPP IV (PmDAP IV) in its free form and in complexes with two kinds of dipeptides as well as with a non-peptidyl inhibitor at 1.90 to 2.47 Å resolution. Acyl-enzyme intermediates were observed for the dipeptide complexes of PmDAP IV, whereas tetrahedral intermediates were reported for the oligopeptide complexes of mammalian DPP IVs. This variation reflects the different structural environments of the active site Arg residues, which are involved in the recognition of a substrate carbonyl group, of mammalian and bacterial enzymes. A phylogenetic analysis revealed that PmDAP IV is a closer relative of dipeptidyl peptidases 8 and 9 (DPP8 and DPP9, DPP IV-family enzymes) than DPP IV. These results provide new insights into the substrate recognition mechanism of bacterial DAP IVs and may assist in the development of selective inhibitors for DAP IVs from pathogenic asaccharolytic bacteria, which utilise proteins or peptides as an energy source.",2018 Feb 9,"['Roppongi, Saori', 'Suzuki, Yoshiyuki', 'Tateoka, Chika', 'Fujimoto, Mayu', 'Morisawa, Saori', 'Iizuka, Ippei', 'Nakamura, Akihiro', 'Honma, Nobuyuki', 'Shida, Yosuke', 'Ogasawara, Wataru', 'Tanaka, Nobutada', 'Sakamoto, Yasumitsu', 'Nonaka, Takamasa']",Sci Rep,,,True
85f1673bfed6603562d3ff8e915f3c6f37fca602,PMC,TRIM56-mediated monoubiquitination of cGAS for cytosolic DNA sensing,http://dx.doi.org/10.1038/s41467-018-02936-3,PMC5807518,29426904,CC BY,"Intracellular nucleic acid sensors often undergo sophisticated modifications that are critical for the regulation of antimicrobial responses. Upon recognition of DNA, the cytosolic sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the second messenger cGAMP, which subsequently initiates downstream signaling to induce interferon-αβ (IFNαβ) production. Here we report that TRIM56 E3 ligase-induced monoubiquitination of cGAS is important for cytosolic DNA sensing and IFNαβ production to induce anti-DNA viral immunity. TRIM56 induces the Lys335 monoubiquitination of cGAS, resulting in a marked increase of its dimerization, DNA-binding activity, and cGAMP production. Consequently, TRIM56-deficient cells are defective in cGAS-mediated IFNαβ production upon herpes simplex virus-1 (HSV-1) infection. Furthermore, TRIM56-deficient mice show impaired IFNαβ production and high susceptibility to lethal HSV-1 infection but not to influenza A virus infection. This adds TRIM56 as a crucial component of the cytosolic DNA sensing pathway that induces anti-DNA viral innate immunity.",2018 Feb 9,"['Seo, Gil Ju', 'Kim, Charlotte', 'Shin, Woo-Jin', 'Sklan, Ella H.', 'Eoh, Hyungjin', 'Jung, Jae U.']",Nat Commun,,,False
389324c342c6ff234b347b72e5cb38d4f4810d39,PMC,TRIM56-mediated monoubiquitination of cGAS for cytosolic DNA sensing,http://dx.doi.org/10.1038/s41467-018-02936-3,PMC5807518,29426904,CC BY,"Intracellular nucleic acid sensors often undergo sophisticated modifications that are critical for the regulation of antimicrobial responses. Upon recognition of DNA, the cytosolic sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the second messenger cGAMP, which subsequently initiates downstream signaling to induce interferon-αβ (IFNαβ) production. Here we report that TRIM56 E3 ligase-induced monoubiquitination of cGAS is important for cytosolic DNA sensing and IFNαβ production to induce anti-DNA viral immunity. TRIM56 induces the Lys335 monoubiquitination of cGAS, resulting in a marked increase of its dimerization, DNA-binding activity, and cGAMP production. Consequently, TRIM56-deficient cells are defective in cGAS-mediated IFNαβ production upon herpes simplex virus-1 (HSV-1) infection. Furthermore, TRIM56-deficient mice show impaired IFNαβ production and high susceptibility to lethal HSV-1 infection but not to influenza A virus infection. This adds TRIM56 as a crucial component of the cytosolic DNA sensing pathway that induces anti-DNA viral innate immunity.",2018 Feb 9,"['Seo, Gil Ju', 'Kim, Charlotte', 'Shin, Woo-Jin', 'Sklan, Ella H.', 'Eoh, Hyungjin', 'Jung, Jae U.']",Nat Commun,,,False
9313219675ddfa18b0667b701433123acc3c39da,PMC,TRIM56-mediated monoubiquitination of cGAS for cytosolic DNA sensing,http://dx.doi.org/10.1038/s41467-018-02936-3,PMC5807518,29426904,CC BY,"Intracellular nucleic acid sensors often undergo sophisticated modifications that are critical for the regulation of antimicrobial responses. Upon recognition of DNA, the cytosolic sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the second messenger cGAMP, which subsequently initiates downstream signaling to induce interferon-αβ (IFNαβ) production. Here we report that TRIM56 E3 ligase-induced monoubiquitination of cGAS is important for cytosolic DNA sensing and IFNαβ production to induce anti-DNA viral immunity. TRIM56 induces the Lys335 monoubiquitination of cGAS, resulting in a marked increase of its dimerization, DNA-binding activity, and cGAMP production. Consequently, TRIM56-deficient cells are defective in cGAS-mediated IFNαβ production upon herpes simplex virus-1 (HSV-1) infection. Furthermore, TRIM56-deficient mice show impaired IFNαβ production and high susceptibility to lethal HSV-1 infection but not to influenza A virus infection. This adds TRIM56 as a crucial component of the cytosolic DNA sensing pathway that induces anti-DNA viral innate immunity.",2018 Feb 9,"['Seo, Gil Ju', 'Kim, Charlotte', 'Shin, Woo-Jin', 'Sklan, Ella H.', 'Eoh, Hyungjin', 'Jung, Jae U.']",Nat Commun,,,True
08467794d024d78c7981f7c39743a9faaa1adecb,PMC,Oral recombinant Lactobacillus vaccine targeting the intestinal microfold cells and dendritic cells for delivering the core neutralizing epitope of porcine epidemic diarrhea virus,http://dx.doi.org/10.1186/s12934-018-0861-7,PMC5807822,29426335,CC BY,"BACKGROUND: Porcine epidemic diarrhea caused by porcine epidemic diarrhea virus (PEDV) has led to serious economic losses to the swine industry worldwide. In this study, an oral recombinant Lactobacillus casei vaccine against PEDV infection targeting the intestinal microfold (M) cells and dendritic cells (DCs) for delivering the core neutralizing epitope (COE) of PEDV spike protein was developed with M cell-targeting peptide (Col) and dendritic cell-targeting peptide (DCpep). The immunogenicity of the orally administered recombinant strains was evaluated. RESULTS: After immunization, significantly higher levels of anti-PEDV specific IgG antibodies with PEDV neutralizing activity in the sera and mucosal sIgA antibodies in the tractus genitalis, intestinal mucus, and stools were detected in mice orally administered with the recombinant strain pPG-COE-Col-DCpep/L393, which expressed DCpep and Col targeting ligands fused with the PEDV COE antigen, compared to mice orally immunized with the recombinant strain pPG-COE/L393 without the DCpep and Col targeting ligands. Moreover, in response to restimulation with the PEDV COE antigen in vitro, a significant difference in splenocyte proliferation response and Th2-associated cytokine IL-4 level was observed in the group of mice orally immunized with pPG-COE-Col-DCpep/L393 (p < 0.05) compared to the groups of mice that received pPG-COE-Col/L393 and pPG-COE-DCpep/L393, respectively. CONCLUSIONS: The intestinal M cells- and DCs-targeting oral delivery of genetically engineered Lactobacillus expressing the COE antigen of PEDV can efficiently induce anti-PEDV mucosal, humoral, and cellular immune responses via oral administration, suggesting a promising vaccine strategy against PEDV infection. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12934-018-0861-7) contains supplementary material, which is available to authorized users.",2018 Feb 9,"['Ma, Sunting', 'Wang, Li', 'Huang, Xuewei', 'Wang, Xiaona', 'Chen, Su', 'Shi, Wen', 'Qiao, Xinyuan', 'Jiang, Yanping', 'Tang, Lijie', 'Xu, Yigang', 'Li, Yijing']",Microb Cell Fact,,,True
8485271eeb378baa284392c0d7174a5612463048,PMC,Use of Peptides for the Management of Alzheimer’s Disease: Diagnosis and Inhibition,http://dx.doi.org/10.3389/fnagi.2018.00021,PMC5808296,29467644,CC BY,"Alzheimer’s disease (AD) is a form of dementia and the most common progressive neurodegenerative disease (ND). The targeting of amyloid-beta (Aβ) aggregation is one of the most widely used strategies to manage AD, and efforts are being made globally to develop peptide-based compounds for the early diagnosis and treatment of AD. Here, we briefly discuss the use of peptide-based compounds for the early diagnosis and treatment of AD and the use of peptide-based inhibitors targeting various Aβ aggregation checkpoints. In addition, we briefly discuss recent applications of peptide-based inhibitors against various AD targets including amyloid beta, β-site amyloid precursor protein cleaving enzyme 1 (BACE1), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), tyrosine phosphatase (TP) and potassium channel KV1.3.",2018 Feb 7,"['Baig, Mohammad H.', 'Ahmad, Khurshid', 'Rabbani, Gulam', 'Choi, Inho']",Front Aging Neurosci,,,True
47dffc938eba5dd824d4f715af096791b0d2d04b,PMC,Surfactant Protein D in Respiratory and Non-Respiratory Diseases,http://dx.doi.org/10.3389/fmed.2018.00018,PMC5809447,29473039,CC BY,"Surfactant protein D (SP-D) is a multimeric collectin that is involved in innate immune defense and expressed in pulmonary, as well as non-pulmonary, epithelia. SP-D exerts antimicrobial effects and dampens inflammation through direct microbial interactions and modulation of host cell responses via a series of cellular receptors. However, low protein concentrations, genetic variation, biochemical modification, and proteolytic breakdown can induce decomposition of multimeric SP-D into low-molecular weight forms, which may induce pro-inflammatory SP-D signaling. Multimeric SP-D can decompose into trimeric SP-D, and this process, and total SP-D levels, are partly determined by variation within the SP-D gene, SFTPD. SP-D has been implicated in the development of respiratory diseases including respiratory distress syndrome, bronchopulmonary dysplasia, allergic asthma, and chronic obstructive pulmonary disease. Disease-induced breakdown or modifications of SP-D facilitate its systemic leakage from the lung, and circulatory SP-D is a promising biomarker for lung injury. Moreover, studies in preclinical animal models have demonstrated that local pulmonary treatment with recombinant SP-D is beneficial in these diseases. In recent years, SP-D has been shown to exert antimicrobial and anti-inflammatory effects in various non-pulmonary organs and to have effects on lipid metabolism and pro-inflammatory effects in vessel walls, which enhance the risk of atherosclerosis. A common SFTPD polymorphism is associated with atherosclerosis and diabetes, and SP-D has been associated with metabolic disorders because of its effects in the endothelium and adipocytes and its obesity-dampening properties. This review summarizes and discusses the reported genetic associations of SP-D with disease and the clinical utility of circulating SP-D for respiratory disease prognosis. Moreover, basic research on the mechanistic links between SP-D and respiratory, cardiovascular, and metabolic diseases is summarized. Perspectives on the development of SP-D therapy are addressed.",2018 Feb 8,"Sorensen, Grith L.",Front Med (Lausanne),,,True
47af8168767ac2a465a3744cffea615594a982fa,PMC,Ethical and Philosophical Considerations for Gain-of-Function Policy: The Importance of Alternate Experiments,http://dx.doi.org/10.3389/fbioe.2018.00011,PMC5809449,29473036,CC BY,"The Department of Health and Human Services Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens (PPPs) contains a series of principles for governing the funding and conduct of gain-of-function (GOF) research resulting in the creation of PPPs. In this article, I address one of these principles, governing the replacement of GOF research with alternate experiments. I argue that the principle fails to address the way that different experiments can promote the same values as those promoted by GOF research resulting in PPPs. I then address some objections to this claim, and provide policy recommendations moving forward.",2018 Feb 8,"Evans, Nicholas Greig",Front Bioeng Biotechnol,,,True
558eec44990e2c8c43145a48bcae68219ae2ba52,PMC,"Mortality estimates among adult patients with severe acute respiratory infections from two sentinel hospitals in southern Arizona, United States, 2010–2014",http://dx.doi.org/10.1186/s12879-018-2984-1,PMC5809880,29433471,CC BY,"BACKGROUND: From October 2010 through February 2016, Arizona conducted surveillance for severe acute respiratory infections (SARI) among adults hospitalized in the Arizona-Mexico border region. There are few accurate mortality estimates in SARI patients, particularly in adults ≥ 65 years old. The purpose of this study was to generate mortality estimates among SARI patients that include deaths occurring shortly after hospital discharge and identify risk factors for mortality. METHODS: Patients admitted to two sentinel hospitals between 2010 and 2014 who met the SARI case definition were enrolled. Demographic data were used to link SARI patients to Arizona death certificates. Mortality within 30 days after the date of admission was calculated and risk factors were identified using logistic regression models. RESULTS: Among 258 SARI patients, 47% were females, 51% were white, non-Hispanic and 39% were Hispanic. The median age was 63 years (range, 19 to 97 years) and 80% had one or more pre-existing health condition; 9% died in hospital. Mortality increased to 12% (30/258, 30% increase) when electronic vital records and a 30-day post-hospitalization time frame were used. Being age ≥ 65 years (OR = 4.0; 95% CI: 1.6–9.9) and having an intensive care unit admission (OR = 7.4; 95% CI: 3.0–17.9) were independently associated with mortality. CONCLUSION: The use of electronic vital records increased SARI-associated mortality estimates by 30%. These findings may help guide prevention and treatment measures, particularly in high-risk persons in this highly fluid border population.",2018 Feb 12,"['Barnes, Steve R.', 'Wansaula, Zimy', 'Herrick, Kristen', 'Oren, Eyal', 'Ernst, Kacey', 'Olsen, Sonja J.', 'Casal, Mariana G.']",BMC Infect Dis,,,True
04d638b3c1d8b8fcd771e569e439b364d4ac2c1a,PMC,Evaluation of the Luminex xTAG Respiratory Viral Panel FAST v2 assay for detection of multiple respiratory viral pathogens in nasal and throat swabs in Vietnam,http://dx.doi.org/10.12688/wellcomeopenres.12429.2,PMC5811805,29503874,CC BY,"Background: Acute respiratory infections (ARI) are among the leading causes of hospitalization in children ≤5 years old. Rapid diagnostics of viral pathogens is essential to avoid unnecessary antibiotic treatment, thereby slowing down antibiotic-resistance. We evaluated the diagnostic performance of the Luminex xTAG Respiratory Viral Panel FAST v2 against viral specific PCR as reference assays for ARI in Vietnam. Methods: Four hundred and forty two nose and throat swabs were collected in viral transport medium, and were tested with Luminex xTAG Respiratory Viral Panel FAST v2. Multiplex RT-PCR and single RT-PCR were used as references.    Results: Overall, sensitivity of the Luminex against reference assays was 91.8%, 95% CI 88.1-94.7 (270/294), whilst 112/6336 (1.8%, 95% CI, 1.4-2.1) of pathogens were detected by the Luminex, but not by reference assays. Frequency of pathogens detected by Luminex and reference assays was 379 and 292, respectively. The diagnostic yield was 66.7% (295/442, 95%CI 62.1-71.1%) for the Luminex assay and 54.1% (239/442, 95% CI, 49.3-58.8%) for reference assays. The Luminex kit had higher yields for all viruses except influenza B virus, respiratory syncytial virus, and human bocavirus. High agreements between both methods [mean (range): 0.91 (0.83-1.00)] were found for 10/15 viral agents. Conclusions: The Luminex assay is a high throughput multiplex platform for rapid detection of common viral pathogens causing ARI. Although the current high cost may prevent Luminex assays from being widely used, especially in limited resource settings where ARI are felt most, its introduction in clinical diagnostics may help reduce unnecessary use of antibiotic prescription.",2018 Apr 30,"['Thi Ty Hang, Vu', 'Thi Han Ny, Nguyen', 'My Phuc, Tran', 'Thi Thanh Tam, Pham', 'Thao Huong, Dang', 'Dang Trung Nghia, Ho', 'Tran Anh Vu, Nguyen', 'Thi Hong Phuong, Pham', 'Van Xang, Nguyen', 'Dong, Nguyen', 'Nhu Hiep, Pham', 'Van Hung, Nguyen', 'Tinh Hien, Tran', 'Rabaa, Maia', 'Thwaites, Guy E.', 'Baker, Stephen', 'Van Tan, Le', 'van Doorn, H.Rogier', None]",Wellcome Open Res,,,True
64fbda4f1a32fd2610ce90ef77b775ec4676bec8,PMC,Detection of potentially novel paramyxovirus and coronavirus viral RNA in bats and rats in the Mekong Delta region of southern Viet Nam,http://dx.doi.org/10.1111/zph.12362,PMC5811810,28418192,CC BY,"Bats and rodents are being increasingly recognized as reservoirs of emerging zoonotic viruses. Various studies have investigated bat viruses in tropical regions, but to date there are no data regarding viruses with zoonotic potential that circulate in bat and rat populations in Viet Nam. To address this paucity of data, we sampled three bat farms and three wet markets trading in rat meat in the Mekong Delta region of southern Viet Nam. Faecal and urine samples were screened for the presence of RNA from paramyxoviruses, coronaviruses and filoviruses. Paramyxovirus RNA was detected in 4 of 248 (1%) and 11 of 222 (4.9%) bat faecal and urine samples, respectively. Coronavirus RNA was detected in 55 of 248 (22%) of bat faecal samples; filovirus RNA was not detected in any of the bat samples. Further, coronavirus RNA was detected in 12 of 270 (4.4%) of rat faecal samples; all samples tested negative for paramyxovirus. Phylogenetic analysis revealed that the bat paramyxoviruses and bat and rat coronaviruses were related to viruses circulating in bat and rodent populations globally, but showed no cross‐species mixing of viruses between bat and rat populations within Viet Nam. Our study shows that potentially novel variants of paramyxoviruses and coronaviruses commonly circulate in bat and rat populations in Viet Nam. Further characterization of the viruses and additional human and animal surveillance is required to evaluate the likelihood of viral spillover and to assess whether these viruses pose a risk to human health.",2018 Feb 18,"['Berto, A.', 'Anh, P. H.', 'Carrique‐Mas, J. J.', 'Simmonds, P.', 'Van Cuong, N.', 'Tue, N. T.', 'Van Dung, N.', 'Woolhouse, M. E.', 'Smith, I.', 'Marsh, G. A.', 'Bryant, J. E.', 'Thwaites, G. E.', 'Baker, S.', 'Rabaa, M. A.', None, 'Kiet, Bach Tuan', 'Boni, Maciej F.', 'Phu, Bui Duc', 'Campbell, James I', 'Hung, Dang Manh', 'Huong, Dang Thao', 'Oanh, Dang Tram', 'Day, Jeremy N.', 'Van Tan, Dinh', 'van Doorn, H. Rogier', 'Han, Duong An', 'Farrar, Jeremy J', 'Trang, Hau Thi Thu', 'Nghia, Ho Dang Trung', 'Long, Hoang Bao', 'Van Duong, Hoang', 'Thu, Huynh Thi Kim', 'Cuong, Lam Chi', 'Hung, Manh', 'Phuong, Thanh', 'Phuc, Thi', 'Phuong, Thi', 'Luat, Xuan', 'Ha, Luu Thi Thu', 'Van Chuong, Ly', 'Loan, Mai Thi Phuoc', 'Nadjm, Behzad', 'Bao, Ngo Thanh', 'Tu, Nguyen Canh', 'Thuan, Nguyen Dac', 'Dong, Nguyen', 'Chuyen, Nguyen Khac', 'An, Nguyen Ngoc', 'Vinh, Nguyen Ngoc', 'Hung, Nguyen Quoc', 'Dung, Nguyen Thanh', 'Minh, Nguyen Thanh', 'Binh, Nguyen Thi', 'Tham, Nguyen Thi Hong', 'Tien, Nguyen Thi Hong', 'Chuc, Nguyen Thi Kim', 'Le Ngoc, Nguyen Thi', 'Ha, Nguyen Thi Lien', 'Lien, Nguyen Thi Nam', 'Diep, Nguyen Thi Ngoc', 'Nhung, Nguyen Thi', 'Chau, Nguyen Thi Song', 'Chi, Nguyen Thi Yen', 'Trinh, Nguyen Thieu', 'Van, Nguyen Thu', 'Van Hung, Nguyen', 'Van Kinh, Nguyen', 'Van Minh Hoang, Nguyen', 'Van My, Nguyen', 'Van Thang, Nguyen', 'Van Thanh, Nguyen', 'Van Vinh Chau, Nguyen', 'Van Xang, Nguyen', 'My, Pham Ha', 'Khoa, Pham Thi Minh', 'Tam, Pham Thi Thanh', 'Van Lao, Pham', 'Van Minh, Pham', 'Van Be Bay, Phan', 'Rahman, Motiur', 'Thompson, Corinne', 'Ngan, Ta Thi Dieu', 'Nhu, Tran Do Hoang', 'Chau, Tran Hoang Minh', 'Toan, Tran Khanh', 'Phuc, Tran My', 'Hong, Tran Thi Kim', 'Dung, Tran Thi Ngoc', 'Thanh, Tran Thi Thanh', 'Minh, Tran Thi Thuy', 'Nguyen, Tran Thua', 'Hien, Tran Tinh', 'Tri, Trinh Quang', 'Hien, Vo Be', 'Tai, Vo Nhut', 'Cuong, Vo Quoc', 'Phat, Voong Vinh', 'Huong, Vu Thi Lan', 'Hang, Vu Thi Ty', 'Wertheim, Heiman', 'Bogaardt, Carlijn', 'Brierley, Liam', 'Chase‐Topping, Margo', 'Ivens, Al', 'Lu, Lu', 'Rambaut, Andrew', 'Woolhouse, Mark', 'Cotten, Matthew', 'Oude Munnink, Bas B.', 'Kellam, Paul', 'Phan, My Vu Tra', 'van der Hoek, Lia', 'Deijs, Martin', 'Jebbink, Maarten F.', 'Farsani, Seyed Mohammad Jazaeri', 'Saylors, Karen', 'Wolfe, Nathan']",Zoonoses Public Health,,,True
e27de1e584ddc112681240ed674464f524869e3a,PMC,Real-time fluorescence loop-mediated isothermal amplification assay for direct detection of egg drop syndrome virus,http://dx.doi.org/10.1186/s12917-018-1364-9,PMC5811957,29439721,CC BY,"BACKGROUND: Egg drop syndrome (EDS), caused by the adenovirus “egg drop syndrome virus” (EDSV) causes severe economic losses through reduced egg production in breeder and layer flocks. The diagnosis of EDSV has been done by molecular tools since its complete genome sequence was identified. In order to enhance the capabilities of the real-time fluorescence loop-mediated isothermal amplification (RealAmp) assay, we aimed to apply the method for direct detection of the EDSV without viral DNA extraction. In order to detect the presence of the EDSV DNA, three pairs of primers were designed, from the conserved region of fiber gene of the EDSV. RESULTS: For our assay, test and control samples were directly used in the reaction mixture in 10-fold serial dilution. The target DNA was amplified at 65 °C, which yield positive results in a relatively short period of 40–45 min. The method reported in this study is highly sensitive as compared to polymerase chain reaction (PCR) and showed no sign of cross-reactivity or false positive results. The RealAmp accomplished specific identification of EDSV among a variety of poultry disease viruses. CONCLUSIONS: The direct RealAmp can be used to detect the presence of EDSV. As our result showed, the RealAmp method could be suitable for the direct detection of other DNA viruses.",2018 Feb 13,"['Zheney, Makay', 'Kaziyev, Zhambul', 'Kassenova, Gulmira', 'Zhao, Lingna', 'Liu, Wei', 'Liang, Lin', 'Li, Gang']",BMC Vet Res,,,True
eb5dcf1546dae050e8aa82aecc2d4b2cc472cbc4,PMC,Molecular characteristics and successful management of a respiratory syncytial virus outbreak among pediatric patients with hemato-oncological disease,http://dx.doi.org/10.1186/s13756-018-0316-2,PMC5812225,29449938,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is responsible for upper and lower respiratory tract infection in adults and children. Especially immunocompromised patients are at high risk for a severe course of infection, and mortality is increased. Moreover RSV can spread in healthcare settings and can cause outbreaks. Herein we demonstrate the successful control and characteristics of a RSV outbreak that included 8 patients in our Department of Pediatric Hematology and Oncology. METHODS: We performed an epidemiologic investigation and a molecular analysis of the outbreak strains. Moreover we present the outbreak control bundle and our concept for RSV screening in the winter season. RESULTS: RSV A and B strains caused the outbreak. RSV B strains affected 3 patients, 2 of whom were co-infected with RSV A. Exactly this RSV A strain was detected in another 5 patients. Our multimodal infection control bundle including prophylactic RSV screening was able to rapidly stop the outbreak. CONCLUSION: An infection control bundle in RSV outbreaks should address all potential transmission pathways. In pediatric settings the restriction of social activities might have a temporal negative impact on quality of life but helps to limit transmission opportunities. Molecular analysis allows better understanding of RSV outbreaks and, if done in a timely manner, might be helpful for guidance of infection control measures.",2018 Feb 13,"['Baier, Claas', 'Haid, Sibylle', 'Beilken, Andreas', 'Behnert, Astrid', 'Wetzke, Martin', 'Brown, Richard J. P.', 'Schmitt, Corinna', 'Ebadi, Ella', 'Hansen, Gesine', 'Schulz, Thomas F.', 'Pietschmann, Thomas', 'Bange, Franz-Christoph']",Antimicrob Resist Infect Control,,,True
4f2216e3b39b7303a9e4d7df96874542c853a3a5,PMC,SeMet attenuates OTA-induced PCV2 replication promotion by inhibiting autophagy by activating the AKT/mTOR signaling pathway,http://dx.doi.org/10.1186/s13567-018-0508-z,PMC5812231,29439710,CC BY,"Porcine circovirus type 2 (PCV2) is recognized as the causative agent of porcine circovirus-associated diseases. PCV2 replication could be promoted by low doses of ochratoxin A (OTA) as in our previous study and selenium has been shown to attenuate PCV2 replication. However, the underlying mechanism remains unclear. The aim of the study was to investigate the effects of selenomethionine (SeMet), the major component of organic selenium, on OTA-induced PCV2 replication promotion and its potential mechanism. The present study demonstrates that OTA could promote PCV2 replication as measured by cap protein expression, viral titer, viral DNA copies and the number of infected cells. In addition, OTA could activate autophagy as indicated by up-regulated light chain 3 (LC3)-II and autophagy-related protein 5 expressions and autophagosome formation. Further, OTA could down-regulate p-AKT and p-mTOR expressions and OTA-induced autophagy was inhibited when insulin was applied. SeMet at 2, 4 and 6 μM had significant inhibiting effects against OTA-induced PCV2 replication promotion. Furthermore, SeMet could attenuate OTA-induced autophagy and up-regulate OTA-induced p-AKT and p-mTOR expression inhibition. Rapamycin, an inhibitor of AKT/mTOR, could reverse the effects of SeMet on OTA-induced autophagy and the PCV2 replication promotion. In conclusion, SeMet could block OTA-induced PCV2 replication promotion by inhibiting autophagy by activating the AKT/mTOR pathway. Therefore, SeMet supplementation could be an effective prophylactic strategy against PCV2 infections and autophagy may be a potential marker to develop novel anti-PCV2 drugs.",2018 Feb 13,"['Qian, Gang', 'Liu, Dandan', 'Hu, Junfa', 'Gan, Fang', 'Hou, Lili', 'Zhai, Nianhui', 'Chen, Xingxiang', 'Huang, Kehe']",Vet Res,,,True
9952cfc72ce630cae558e4f98680a44b43494247,PMC,A case series on common cold to severe bronchiolitis and pneumonia in children following human metapneumovirus infection in Sri Lanka,http://dx.doi.org/10.1186/s13104-018-3239-3,PMC5813322,29444701,CC BY,"OBJECTIVES: The prevalence of hMPV infections in Sri Lanka has not been reported and here we report a case series of hMPV infection in children less than 5 years. Patients with ARTI were included from Teaching Hospital, Anuradhapura from March 2013 to August 2014. Indirect fluorescence assay was performed on nasopharyngeal aspirates for the identification of respiratory viruses [respiratory syncytial virus (RSV), parainfluenza virus 1, 2 and 3, influenza A and B and hMPV]. Moreover, reverse transcriptase-polymerase chain reaction was done to further confirm the hMPV infection. RESULTS: In this case series, hMPV infection showed a range of respiratory symptoms from common cold to life threatening lower respiratory tract infections with varying severity. In some cases, the clinical presentation of hMPV infection was similar to the ARTI caused by RSV. hMPV co-infections with of RSV have also been seen in some cases of ARTI. A child delivered through cesarean section and birth order > 3 has an Odds ratio of 3.5 and 4.3 (95% CI) for developing co-infection with RSV compared to hMPV mono-infections. Lack of diagnostic facilities to identify the viral aetiology has contributed to the use of antibiotics indicating the need for establishing viral diagnostic facilities in the country. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-018-3239-3) contains supplementary material, which is available to authorized users.",2018 Feb 14,"['Jayaweera, J. A. A. S.', 'Noordeen, F.', 'Kothalaweala, S.', 'Pitchai, F. N. N.', 'Rayes, M. L. M.']",BMC Res Notes,,,True
77b8d67e208f5ba81ff129e0d4ff7e1b73c45482,PMC,"Potential effects of the combination of nicotinamide, vitamin B2 and vitamin C on oxidative-mediated hepatotoxicity induced by thioacetamide",http://dx.doi.org/10.1186/s12944-018-0674-z,PMC5813429,29444683,CC BY,"BACKGROUND: The liver disease is one of the most important traditional public health problems in Egypt. Oxidative stress is attributed to such pathological condition that further contributes to the initiation and progression of liver injury. In the present study, we have investigated if the strong antioxidant power of Nicotinamide (NA), Vitamin B2 (VB2), and Vitamin C (VC) can ameliorate TAA-induced oxidative stress-mediated liver injury in the rats. METHODS: Thirty-six albino rats were divided into six groups: Control group; TAA group (IP injection with TAA at a dosage of 200 mg/Kg three times a week for two months); TAA + NA group (rats administered with NA at a dosage of 200 mg/kg daily besides TAA as in the control); TAA + VB2 group (rats administered with vitamin B2 at a dosage of 30 mg/kg daily besides injection with TAA); TAA + VC group (rats administered with vitamin C at a dosage of 200 mg/kg daily along with injection of TAA). TAA + NA + VB + VC group (rats administered the with the three vitamins daily in TAA pre-injected at the respective doses described above). RESULTS: Treatment of rats with TAA led to a significant elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total bilirubin, cholesterol, triglycerides, low-density lipoprotein (LDL) and tumor necrosis factor-alpha (TNF-α) in the serum samples. Moreover, malondialdehyde (MDA), hydroxyproline and nitic oxide (NO) were also significantly increased in the TAA-treated rats, while reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were significantly compromised in the hepatic samples. Rats administered with NA, VB2, and VC as individually or in combination ameliorated the deleterious effects of TAA that was confirmed by histopathology. However, the combination of the three vitamins was found more effective as compared to each of the vitamins. CONCLUSION: Our work demonstrates that NA, VB2, and VC cross-talk with each other that act as a more potent biochemical chain of antioxidant defense against TAA-induced toxicities in vivo.",2018 Feb 14,"['Bashandy, Samir A. E.', 'Ebaid, Hossam', 'Abdelmottaleb Moussa, Sherif A.', 'Alhazza, Ibrahim M.', 'Hassan, Iftekhar', 'Alaamer, Abdulaziz', 'al Tamimi, Jameel']",Lipids Health Dis,,,True
ec757128aeed391827b41d94e53b3fdb598d9900,PMC,Modern Sunni-Shia conflicts and their neglected tropical diseases,http://dx.doi.org/10.1371/journal.pntd.0006008,PMC5813896,29447164,CC BY,,2018 Feb 15,"Hotez, Peter J.",PLoS Negl Trop Dis,,,True
ba3179ae7ea6877b7b76e048959e97cc0012f5fc,PMC,Virome and bacteriome characterization of children with pneumonia and asthma in Mexico City during winter seasons 2014 and 2015,http://dx.doi.org/10.1371/journal.pone.0192878,PMC5813968,29447223,CC BY,"BACKGROUND: Acute asthma exacerbations and pneumonia are important causes of morbidity and mortality in children and may coexist in the same children, although symptom overlap may lead to difficulties in diagnosis. Microbial and viral diversity and differential abundance of either may play an important role in infection susceptibility and the development of acute and chronic respiratory diseases. OBJECTIVES: To describe the virome and bacteriome present in the upper respiratory tract of hospitalized children with a clinical diagnosis of asthma and pneumonia during an acute exacerbation and an acute respiratory illness ARI episode respectively. METHODS: During the winter seasons of 2013–2014 and 2014–2015, 134 nasopharyngeal swabs samples of children <15 years of age with ARI hospitalized at a referral hospital for respiratory diseases were selected based on clinical diagnosis of asthma or pneumonia. The virome and bacteriome were characterized using Whole Genome Sequencing (WGS) and in-house bioinformatics analysis pipeline. RESULTS: The Asthma group was represented mainly by RV-C, BoV-1 and RSV-B and the pneumonia group by Bacteriophage EJ-1 and TTMV. TTV was found in both groups with a similar amount of reads. About bacterial composition Moraxella catarrhalis, Propionibacterium acnes and Acinetobacter were present in asthma and Veillonella parvula and Mycoplasma pneumoniae in pneumonia. Streptococcus pneumoniae and Haemophilus influenzae were mostly found with both asthma and pneumonia. CONCLUSIONS: Our results show a complex viral and bacterial composition in asthma and pneumonia groups with a strong association of RV-C presence in asthmatic children. We observed Streptococcus pneumoniae and Haemophilus influenzae concurrently in both groups.",2018 Feb 15,"['Romero-Espinoza, Jose A.', 'Moreno-Valencia, Yazmin', 'Coronel-Tellez, Rodrigo H.', 'Castillejos-Lopez, Manuel', 'Hernandez, Andres', 'Dominguez, Aaron', 'Miliar-Garcia, Angel', 'Barbachano-Guerrero, Arturo', 'Perez-Padilla, Rogelio', 'Alejandre-Garcia, Alejandro', 'Vazquez-Perez, Joel A.']",PLoS One,,,True
1522b3c191730bb3161a610fadb3bf06095ab902,PMC,Comparison of viral infection in healthcare-associated pneumonia (HCAP) and community-acquired pneumonia (CAP),http://dx.doi.org/10.1371/journal.pone.0192893,PMC5813982,29447204,CC BY,"BACKGROUND: Although viruses are known to be the second most common etiological factor in community-acquired pneumonia (CAP), the respiratory viral profile of the patients with healthcare-associated pneumonia (HCAP) has not yet been elucidated. We investigated the prevalence and the clinical impact of respiratory virus infection in adult patients with HCAP. METHODS: Patients admitted with HCAP or CAP, between January and December 2016, to a tertiary referral hospital in Korea, were prospectively enrolled, and virus identification was performed using reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: Among 452 enrolled patients (224 with HCAP, 228 with CAP), samples for respiratory viruses were collected from sputum or endotracheal aspirate in 430 (95.1%) patients and from nasopharyngeal specimens in 22 (4.9%) patients. Eighty-seven (19.2%) patients had a viral infection, and the proportion of those with viral infection was significantly lower in the HCAP than in the CAP group (13.8% vs 24.6%, p = 0.004). In both the HCAP and CAP groups, influenza A was the most common respiratory virus, followed by entero-rhinovirus. The seasonal distributions of respiratory viruses were also similar in both groups. In the HCAP group, the viral infection resulted in a similar length of hospital stay and in-hospital mortality as viral–bacterial coinfection and bacterial infection, and the CAP group showed similar results. CONCLUSIONS: The prevalence of viral infection in patients with HCAP was lower than that in patients with CAP, and resulted in a similar prognosis as viral–bacterial coinfection or bacterial infection.",2018 Feb 15,"['Kim, Eun Sun', 'Park, Kyoung Un', 'Lee, Sang Hoon', 'Lee, Yeon Joo', 'Park, Jong Sun', 'Cho, Young-Jae', 'Yoon, Ho Il', 'Lee, Choon-Taek', 'Lee, Jae Ho']",PLoS One,,,True
3391fcc4d89196ca239c043cfb37e68d8d2e370a,PMC,Differences in the intestinal microbiota between uninfected piglets and piglets infected with porcine epidemic diarrhea virus,http://dx.doi.org/10.1371/journal.pone.0192992,PMC5814011,29447243,CC BY,"Porcine epidemic diarrhea, a disastrous gastrointestinal disease, causes great financial losses due to its high infectivity, morbidity and mortality in suckling piglets despite the development and application of various vaccines. In this study, high-throughput sequencing was used to explore differences in the intestinal microbiota between uninfected piglets and piglets infected with porcine epidemic diarrhea virus (PEDV). The results revealed that the small intestinal microbiota of suckling piglets infected with PEDV showed low diversity and was dominated by Proteobacteria (49.1%). Additionally, the composition of the small intestinal microbiota of sucking piglets infected with PEDV showed marked differences from that of the uninfected piglets. Some of the taxa showing differences in abundance between uninfected piglets and piglets infected with PEDV were associated with cellular transport and catabolism, energy metabolism, the biosynthesis of other secondary metabolites, and amino acid metabolism as determined through the prediction of microbial function based on the bacterial 16S rRNA gene. Therefore, adjusting the intestinal microbiota might be a promising method for the prevention or treatment of PEDV.",2018 Feb 15,"['Huang, Mei-Zhou', 'Wang, Sheng-Yi', 'Wang, Hui', 'Cui, Dong-An', 'Yang, Ya-Jun', 'Liu, Xi-Wang', 'Kong, Xiao-Jun', 'Li, Jian-Yong']",PLoS One,,,True
fdf25867c1135bdc7fe68249c3a7f79fa05b9619,PMC,Nuclear targeting of the betanodavirus B1 protein via two arginine-rich domains induces G1/S cell cycle arrest mediated by upregulation of p53/p21,http://dx.doi.org/10.1038/s41598-018-21340-x,PMC5814437,29449573,CC BY,"The molecular functions of betanodavirus non-structural protein B and its role in host cell survival remain unclear. In the present study, we examined the roles of specific nuclear targeting domains in B1 localization as well as the effect of B1 nuclear localization on the cell cycle and host cell survival. The B1 protein of the Red spotted grouper nervous necrosis virus (RGNNV) was detected in GF-1 grouper cells as early as 24 hours post-infection (hpi). Using an EYFP-B1 fusion construct, we observed nuclear localization of the B1 protein (up to 99%) in GF-1 cells at 48 hpi. The nuclear localization of B1 was mediated by two arginine-rich nuclear targeting domains (B domain: (46)RRSRR(51); C domain: (63)RDKRPRR(70)) and domain C was more important than domain B in this process. B1 nuclear localization correlated with upregulation of p53 and p21((wef1/cip1)); downregulation of Cyclin D1, CDK4 and Mdm2; and G1/S cell cycle arrest in GF-1 cells. In conclusion, nuclear targeting of the RGNNV B1 protein via two targeting domains causes cell cycle arrest by up-regulating p53/p21 and down-regulating Mdm2, thereby regulating host cell survival.",2018 Feb 15,"['Su, Yu-Chin', 'Reshi, Latif', 'Chen, Lei-Jia', 'Li, Wei-Han', 'Chiu, Hsuan-Wen', 'Hong, Jiann-Ruey']",Sci Rep,,,True
ad0a78a68ab4c3beade7409be318f0d13046b922,PMC,6-Thioguanine is a noncompetitive and slow binding inhibitor of human deubiquitinating protease USP2,http://dx.doi.org/10.1038/s41598-018-21476-w,PMC5814560,29449607,CC BY,"Ubiquitin-specific protease 2 (USP2) belongs to the family of deubiquitinases that can rescue protein targets from proteasomal degradation by reversing their ubiquitination. In various cancers, including prostate cancer and ovarian carcinoma, upregulation of USP2 leads to an increase in the levels of deubiquitinated substrates such as fatty acid synthase, MDM2, cyclin D1 and Aurora-A. USP2 thus plays a critical role in tumor cells’ survival and therefore represents a therapeutic target. Here a leukemia drug, 6-thioguanine, was found to be a potent inhibitor of USP2. Enzyme-kinetic and X-ray crystallographic data suggest that 6-thioguanine displays a noncompetitive and slow-binding inhibitory mechanism against USP2. Our study provides a clear rationale for the clinical evaluation of 6-thioguanine for USP2-upregulated cancers.",2018 Feb 15,"['Chuang, Shang-Ju', 'Cheng, Shu-Chun', 'Tang, Hui-Chi', 'Sun, Chiao-Yin', 'Chou, Chi-Yuan']",Sci Rep,,,True
8f7a0834ec2f0e699772cf4c647b0f3cb213b54e,PMC,The One Health Concept: 10 Years Old and a Long Road Ahead,http://dx.doi.org/10.3389/fvets.2018.00014,PMC5816263,29484301,CC BY,"Over the past decade, a significant increase in the circulation of infectious agents was observed. With the spread and emergence of epizootics, zoonoses, and epidemics, the risks of pandemics became more and more critical. Human and animal health has also been threatened by antimicrobial resistance, environmental pollution, and the development of multifactorial and chronic diseases. This highlighted the increasing globalization of health risks and the importance of the human–animal–ecosystem interface in the evolution and emergence of pathogens. A better knowledge of causes and consequences of certain human activities, lifestyles, and behaviors in ecosystems is crucial for a rigorous interpretation of disease dynamics and to drive public policies. As a global good, health security must be understood on a global scale and from a global and crosscutting perspective, integrating human health, animal health, plant health, ecosystems health, and biodiversity. In this study, we discuss how crucial it is to consider ecological, evolutionary, and environmental sciences in understanding the emergence and re-emergence of infectious diseases and in facing the challenges of antimicrobial resistance. We also discuss the application of the “One Health” concept to non-communicable chronic diseases linked to exposure to multiple stresses, including toxic stress, and new lifestyles. Finally, we draw up a list of barriers that need removing and the ambitions that we must nurture for the effective application of the “One Health” concept. We conclude that the success of this One Health concept now requires breaking down the interdisciplinary barriers that still separate human and veterinary medicine from ecological, evolutionary, and environmental sciences. The development of integrative approaches should be promoted by linking the study of factors underlying stress responses to their consequences on ecosystem functioning and evolution. This knowledge is required for the development of novel control strategies inspired by environmental mechanisms leading to desired equilibrium and dynamics in healthy ecosystems and must provide in the near future a framework for more integrated operational initiatives.",2018 Feb 12,"['Destoumieux-Garzón, Delphine', 'Mavingui, Patrick', 'Boetsch, Gilles', 'Boissier, Jérôme', 'Darriet, Frédéric', 'Duboz, Priscilla', 'Fritsch, Clémentine', 'Giraudoux, Patrick', 'Le Roux, Frédérique', 'Morand, Serge', 'Paillard, Christine', 'Pontier, Dominique', 'Sueur, Cédric', 'Voituron, Yann']",Front Vet Sci,,,True
87d23553b1e4abc9f23750121d6259b10da73387,PMC,Pathogenicity and Viral Shedding of MERS-CoV in Immunocompromised Rhesus Macaques,http://dx.doi.org/10.3389/fimmu.2018.00205,PMC5816332,29483914,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) has recently emerged in the Middle East. Since 2012, there have been approximately 2,100 confirmed cases, with a 35% case fatality rate. Disease severity has been linked to patient health status, as people with chronic diseases or an immunocompromised status fare worse, although the mechanisms of disease have yet to be elucidated. We used the rhesus macaque model of mild MERS to investigate whether the immune response plays a role in the pathogenicity in relation to MERS-CoV shedding. Immunosuppressed macaques were inoculated with MERS-CoV and sampled daily for 6 days to assess their immune statues and to measure viral shedding and replication. Immunosuppressed macaques supported significantly higher levels of MERS-CoV replication in respiratory tissues and shed more virus, and virus disseminated to tissues outside of the respiratory tract, whereas viral RNA was confined to respiratory tissues in non-immunosuppressed animals. Despite increased viral replication, pathology in the lungs was significantly lower in immunosuppressed animals. The observation that the virus was less pathogenic in these animals suggests that disease has an immunopathogenic component and shows that inflammatory responses elicited by the virus contribute to disease.",2018 Feb 12,"['Prescott, Joseph', 'Falzarano, Darryl', 'de Wit, Emmie', 'Hardcastle, Kath', 'Feldmann, Friederike', 'Haddock, Elaine', 'Scott, Dana', 'Feldmann, Heinz', 'Munster, Vincent Jacobus']",Front Immunol,,,True
2191141163dc621f5b160f741d880e9ce6342e3a,PMC,Clinical implications of rapid ePlex® Respiratory Pathogen Panel testing compared to laboratory-developed real-time PCR,http://dx.doi.org/10.1007/s10096-017-3151-0,PMC5816761,29222697,CC BY,"Rapid diagnosis of respiratory infections is of great importance for adequate isolation and treatment. Due to the batch-wise testing, laboratory-developed real-time polymerase chain reaction (PCR) assays (LDT) often result in a time to result of one day. Here, LDT was compared with rapid ePlex® Respiratory Pathogen (RP) Panel testing of GenMark Diagnostics (Carlsbad, CA, USA) with regard to time to result, installed isolation precautions, and antibacterial/antiviral treatment. Between January and March 2017, 68 specimens of 64 patients suspected of an acute respiratory infection were tested with LDT and the ePlex® RP panel. The time to result was calculated as the time between sample reception and result reporting. Information regarding isolation and antibacterial/antiviral treatment was obtained from the patient records. Thirty specimens tested LDT positive (47%) and 29 ePlex® RP panel positive (45%). The median time to result was 27.1 h (range 6.5–96.6) for LDT versus 3.4 h (range 1.5–23.6) for the RP panel, p-value < 0.001. In 14 out of 30 patients, isolation was discontinued based on the ePlex® RP panel results, saving 21 isolation days. ePlex® RP panel test results were available approximately one day ahead of the LDT results in the 19 patients receiving antiviral/antibacterial treatment. In addition, two bacterial pathogens, not requested by the physician, were detected using the RP panel. Analysis of respiratory infections with the ePlex® RP panel resulted in a significant decrease in time to result, enabling a reduction in isolation days in half of the patients. Furthermore, syndromic RP panel testing increased the identification of causative pathogens.",2018 Dec 8,"['van Rijn, Anneloes L.', 'Nijhuis, Roel H. T.', 'Bekker, Vincent', 'Groeneveld, Geert H.', 'Wessels, Els', 'Feltkamp, Mariet C. W.', 'Claas, Eric C. J.']",Eur J Clin Microbiol Infect Dis,,,True
af475b1445628312443de29d85bff40825d411e0,PMC,Staphylococcus aureus Complex in the Straw-Colored Fruit Bat (Eidolon helvum) in Nigeria,http://dx.doi.org/10.3389/fmicb.2018.00162,PMC5816944,29487577,CC BY,"Bats are economically important animals and serve as food sources in some African regions. They can be colonized with the Staphylococcus aureus complex, which includes Staphylococcus schweitzeri and Staphylococcus argenteus. Fecal carriage of S. aureus complex in the straw-colored fruit bat (Eidolon helvum) has been described. However, data on their transmission and adaptation in animals and humans are limited. The aim of this study was to investigate the population structure of the S. aureus complex in E. helvum and to assess the geographical spread of S. aureus complex among other animals and humans. Fecal samples were collected from E. helvum in Obafemi Awolowo University, Ile-Ife, Nigeria. The isolates were characterized by antimicrobial susceptibility testing, spa typing and multilocus sequence typing (MLST). Isolates were screened for the presence of lukS/lukF-PV and the immune evasion cluster (scn, sak, chp) which is frequently found in isolates adapted to the human host. A Neighbor-Joining tree was constructed using the concatenated sequences of the seven MLST genes. A total of 250 fecal samples were collected and 53 isolates were included in the final analysis. They were identified as S. aureus (n = 28), S. schweitzeri (n = 11) and S. argenteus (n = 14). Only one S. aureus was resistant to penicillin and another isolate was intermediately susceptible to tetracycline. The scn, sak, and chp gene were not detected. Species-specific MLST clonal complexes (CC) were detected for S. aureus (CC1725), S. argenteus (CC3960, CC3961), and S. schweitzeri (CC2463). STs of S. schweitzeri from this study were similar to STs from bats in Nigeria (ST2464) and Gabon (ST1700) or from monkey in Côte d'Ivoire (ST2058, ST2072). This suggests host adaptation of certain clones to wildlife mammals with a wide geographical spread in Africa. In conclusion, there is evidence of fecal carriage of members of S. aureus complex in E. helvum. S. schweitzeri from bats in Nigeria are closely related to those from bats and monkeys in West and Central Africa suggesting a cross-species transmission and wide geographical distribution. The low antimicrobial resistance rates and the absence of the immune evasion cluster suggests a limited exposure of these isolates to humans.",2018 Feb 13,"['Olatimehin, Ayodele', 'Shittu, Adebayo O.', 'Onwugamba, Francis C.', 'Mellmann, Alexander', 'Becker, Karsten', 'Schaumburg, Frieder']",Front Microbiol,,,True
77df12a2ea42f8702db5b87396eebc49d3d13085,PMC,Estimating the burden of influenza‐associated hospitalization and deaths in Oman (2012‐2015),http://dx.doi.org/10.1111/irv.12500,PMC5818336,29205882,CC BY,"BACKGROUND: Influenza is a serious vaccine‐preventable disease with high incidence, hospitalization, and mortality in high‐risk groups. The epidemiology, seasonality, and risk factors for influenza are well defined in most of the temperate countries, but estimating influenza burden in the World Health Organization (WHO) Region for the Eastern Mediterranean is scarce. In Oman, despite the advancements in influenza surveillance, the clinical burden and seasonality of influenza remain not fully understood. OBJECTIVES: To estimate the incidence of influenza‐associated hospitalizations and in‐hospital death in Oman. PATIENTS AND METHODS: Influenza‐associated hospitalizations and in‐hospital deaths were estimated using hospital discharge records based on ICD‐10 codes (J09‐J18), results of virological analysis and population census for the period between 2012 and 2015. RESULTS: During 2012 and 2015, we identified a total of 19 405 influenza‐associated hospitalization and 847 deaths. Influenza positivity percentage ranged from 6.4% in 2013 to 20.6% in 2015. Influenza‐associated hospitalization incidence rate was 7.3 (95% CI: 6.4‐8.1) per 100 000 in 2013 and 27.5 (95% CI: 25.9‐29.1) per 100 000 in 2015 with an overall rate of 20.6 (95% CI: 19.9‐21.3) per 100 000. The highest incidence of influenza‐associated death was among those aged ≥65 years and ranged between 39.5 (95% CI: 27.3‐51.8) per 100 000 in 2014 and 11.3 (95% CI: 7.5‐15.1) in 2015. CONCLUSIONS: Influenza causes a substantial number of hospitalizations and deaths in Oman. Hospitalization rates were highest among children, and adults ≥65 years showed the highest death rate. The potential value of using seasonal influenza vaccine in these groups should be considered.",2018 Jan 5,"['Abdel‐Hady, Doaa M.', 'Al Balushi, Rima M.', 'Al Abri, Badr A.', 'Al Abri, Seif S.', 'Al Kindi, Hanan S.', 'Al‐Jardani, Amina K.', 'Al Yaqubi, Fatma M.', 'Al Abaidani, Idris S.']",Influenza Other Respir Viruses,,,True
91c30e7428918ea501a35e683a5d89c6b45f020a,PMC,Dr. Yang Zhong: An explorer on the road forever,http://dx.doi.org/10.1007/s13238-017-0496-1,PMC5818370,29256009,CC BY,,2018 Feb 18,"['Chen, Fan', 'Lu, Bao-Rong', 'Crabbe, James C.', 'Zhao, Jia-yuan', 'Zhong, Bo-jian', 'Geng, Yu-peng', 'Zheng, Yu-fang', 'Wang, Hong-yan']",Protein Cell,,,True
4091e78b118eed89910b5089f4303a51d7e4c4fa,PMC,Peste des Petits Ruminants Virus Enters Caprine Endometrial Epithelial Cells via the Caveolae-Mediated Endocytosis Pathway,http://dx.doi.org/10.3389/fmicb.2018.00210,PMC5818419,29497407,CC BY,"Peste des petits ruminants virus (PPRV) causes an acute and highly contagious disease of sheep and goats and has spread with alarming speed around the world. The pathology of Peste des petits ruminants is linked to retrogressive changes and necrotic lesions in lymphoid tissues and epithelial cells. However, the process of PPRV entry into host epithelial cells remains largely unknown. Here, we performed a comprehensive study of the entry mechanism of PPRV into caprine endometrial epithelial cells (EECs). We clearly demonstrated that PPRV internalization was inhibited by chloroquine and ammonium chloride, which elevate the pH of various organelles. However, PPRV entry was not affected by chlorpromazine and knockdown of the clathrin heavy chain in EECs. In addition, we found that the internalization of PPRV was dependent on dynamin and membrane cholesterol and was suppressed by silencing of caveolin-1. Macropinocytosis did not play a role, but phosphatidylinositol 3-kinase (PI3K) was required for PPRV internalization. Cell type and receptor-dependent differences indicated that PPRV entry into caprine fetal fibroblast cells (FFCs) occurred via a different route. Taken together, our findings demonstrate that PPRV enters EECs through a cholesterol-dependent caveolae-mediated uptake mechanism that is pH-dependent and requires dynamin and PI3K but is independent of clathrin. This potentially provides insight into the entry mechanisms of other morbilliviruses.",2018 Feb 15,"['Yang, Bo', 'Qi, Xuefeng', 'Guo, Hui', 'Jia, Peilong', 'Chen, Shuying', 'Chen, Zhijie', 'Wang, Ting', 'Wang, Jingyu', 'Xue, Qinghong']",Front Microbiol,,,True
474a502696d79b407fb2ff9f85d1b974d0064bf6,PMC,Molecular Evidence of Adenosine Deaminase Linking Adenosine A(2A) Receptor and CD26 Proteins,http://dx.doi.org/10.3389/fphar.2018.00106,PMC5818423,29497379,CC BY,"Adenosine is an endogenous purine nucleoside that acts in all living systems as a homeostatic network regulator through many pathways, which are adenosine receptor (AR)-dependent and -independent. From a metabolic point of view, adenosine deaminase (ADA) is an essential protein in the regulation of the total intracellular and extracellular adenosine in a tissue. In addition to its cytosolic localization, ADA is also expressed as an ecto-enzyme on the surface of different cells. Dipeptidyl peptidase IV (CD26) and some ARs act as binding proteins for extracellular ADA in humans. Since CD26 and ARs interact with ADA at opposite sites, we have investigated if ADA can function as a cell-to-cell communication molecule by bridging the anchoring molecules CD26 and A(2A)R present on the surfaces of the interacting cells. By combining site-directed mutagenesis of ADA amino acids involved in binding to A(2A)R and a modification of the bioluminescence resonance energy transfer (BRET) technique that allows detection of interactions between two proteins expressed in different cell populations with low steric hindrance (NanoBRET), we show direct evidence of the specific formation of trimeric complexes CD26-ADA-A(2A)R involving two cells. By dynamic mass redistribution assays and ligand binding experiments, we also demonstrate that A(2A)R-NanoLuc fusion proteins are functional. The existence of this ternary complex is in good agreement with the hypothesis that ADA could bridge T-cells (expressing CD26) and dendritic cells (expressing A(2A)R). This is a new metabolic function for ecto-ADA that, being a single chain protein, it has been considered as an example of moonlighting protein, because it performs more than one functional role (as a catalyst, a costimulator, an allosteric modulator and a cell-to-cell connector) without partitioning these functions in different subunits.",2018 Feb 15,"['Moreno, Estefanía', 'Canet, Júlia', 'Gracia, Eduard', 'Lluís, Carme', 'Mallol, Josefa', 'Canela, Enric I.', 'Cortés, Antoni', 'Casadó, Vicent']",Front Pharmacol,,,True
1ed7ba58402344abc5e614e344d03a30c03164af,PMC,Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model,http://dx.doi.org/10.3389/fimmu.2018.00229,PMC5818468,29497420,CC BY,"Myalgic encephalomyelitis (ME) often also called chronic fatigue syndrome (ME/CFS) is a common, debilitating, disease of unknown origin. Although a subject of controversy and a considerable scientific literature, we think that a solid understanding of ME/CFS pathogenesis is emerging. In this study, we compiled recent findings and placed them in the context of the clinical picture and natural history of the disease. A pattern emerged, giving rise to an explanatory model. ME/CFS often starts after or during an infection. A logical explanation is that the infection initiates an autoreactive process, which affects several functions, including brain and energy metabolism. According to our model for ME/CFS pathogenesis, patients with a genetic predisposition and dysbiosis experience a gradual development of B cell clones prone to autoreactivity. Under normal circumstances these B cell offsprings would have led to tolerance. Subsequent exogenous microbial exposition (triggering) can lead to comorbidities such as fibromyalgia, thyroid disorder, and orthostatic hypotension. A decisive infectious trigger may then lead to immunization against autoantigens involved in aerobic energy production and/or hormone receptors and ion channel proteins, producing postexertional malaise and ME/CFS, affecting both muscle and brain. In principle, cloning and sequencing of immunoglobulin variable domains could reveal the evolution of pathogenic clones. Although evidence consistent with the model accumulated in recent years, there are several missing links in it. Hopefully, the hypothesis generates testable propositions that can augment the understanding of the pathogenesis of ME/CFS.",2018 Feb 15,"['Blomberg, Jonas', 'Gottfries, Carl-Gerhard', 'Elfaitouri, Amal', 'Rizwan, Muhammad', 'Rosén, Anders']",Front Immunol,,,True
ee0c318d282c0089cca94f0b2ea4d90db2ab9f8a,PMC,Obesity and risk of respiratory tract infections: results of an infection-diary based cohort study,http://dx.doi.org/10.1186/s12889-018-5172-8,PMC5819164,29458350,CC BY,"BACKGROUND: Respiratory tract infections (RTIs) are a major morbidity factor contributing largely to health care costs and individual quality of life. The aim of the study was to test whether obesity (BMI ≥ 30 kg/m(2)) is one of the risk factors underlying frequent RTIs in the German adult population. METHODS: We recruited 1455 individuals between 18 to 70 years from a cross-sectional survey on airway infections in Germany and invited them to self-report in diaries incident RTIs experienced during three consecutive winter/spring seasons. RTIs reported in these 18 months and summary measures adding-up individual RTIs were the outcomes of interest. RESULTS: Compared to individuals with normal weight, obese individuals reported a consistently higher frequency of upper and lower RTIs and predominantly fell in the upper 10% group of a diary sumscore adding-up 10 different RTI symptoms over time. Obesity was associated both with lower RTIs ((adjusted)OR = 2.02, 95%CI = 1.36–3.00) and upper RTIs ((adjusted)OR = 1.55, 95%CI = 1.22–1.96). Adjusting for demographic and lifestyle variables did only marginally affect ORs. Stratified analyses suggested a stronger association for women and effect modifications by sports activity and dietary habits. CONCLUSIONS: We confirm the association of obesity with infection burden and present evidence for putative interaction with sports activity and dietary patterns. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-018-5172-8) contains supplementary material, which is available to authorized users.",2018 Feb 20,"['Maccioni, Livia', 'Weber, Susanne', 'Elgizouli, Magdeldin', 'Stoehlker, Anne-Sophie', 'Geist, Ilona', 'Peter, Hans-Hartmut', 'Vach, Werner', 'Nieters, Alexandra']",BMC Public Health,,,True
36dd734bdaca97dee8606b4aa7c92dc1e043ae2f,PMC,A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera,http://dx.doi.org/10.1186/s12866-018-1154-3,PMC5819196,29458340,CC BY,"BACKGROUND: Recurrent acute otitis media (rAOM, recurrent ear infection) is a common childhood disease caused by bacteria termed otopathogens, for which current treatments have limited effectiveness. Generic probiotic therapies have shown promise, but seem to lack specificity. We hypothesised that healthy children with no history of AOM carry protective commensal bacteria that could be translated into a specific probiotic therapy to break the cycle of re-infection. We characterised the nasopharyngeal microbiome of these children (controls) in comparison to children with rAOM (cases) to identify potentially protective bacteria. As some children with rAOM do not appear to carry any of the known otopathogens, we also hypothesised that characterisation of the middle ear microbiome could identify novel otopathogens, which may also guide the development of more effective therapies. RESULTS: Middle ear fluids, middle ear rinses and ear canal swabs from the cases and nasopharyngeal swabs from both groups underwent 16S rRNA gene sequencing. The nasopharyngeal microbiomes of cases and controls were distinct. We observed a significantly higher abundance of Corynebacterium and Dolosigranulum in the nasopharynx of controls. Alloiococcus, Staphylococcus and Turicella were abundant in the middle ear and ear canal of cases, but were uncommon in the nasopharynx of both groups. Gemella and Neisseria were characteristic of the case nasopharynx, but were not prevalent in the middle ear. CONCLUSIONS: Corynebacterium and Dolosigranulum are characteristic of a healthy nasopharyngeal microbiome. Alloiococcus, Staphylococcus and Turicella are possible novel otopathogens, though their rarity in the nasopharynx and prevalence in the ear canal means that their role as normal aural flora cannot be ruled out. Gemella and Neisseria are unlikely to be novel otopathogens as they do not appear to colonise the middle ear in children with rAOM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12866-018-1154-3) contains supplementary material, which is available to authorized users.",2018 Feb 20,"['Lappan, Rachael', 'Imbrogno, Kara', 'Sikazwe, Chisha', 'Anderson, Denise', 'Mok, Danny', 'Coates, Harvey', 'Vijayasekaran, Shyan', 'Bumbak, Paul', 'Blyth, Christopher C.', 'Jamieson, Sarra E.', 'Peacock, Christopher S.']",BMC Microbiol,,,False
59bb7fb884f99d99bf751236a9981de7b4cf77c5,PMC,A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera,http://dx.doi.org/10.1186/s12866-018-1154-3,PMC5819196,29458340,CC BY,"BACKGROUND: Recurrent acute otitis media (rAOM, recurrent ear infection) is a common childhood disease caused by bacteria termed otopathogens, for which current treatments have limited effectiveness. Generic probiotic therapies have shown promise, but seem to lack specificity. We hypothesised that healthy children with no history of AOM carry protective commensal bacteria that could be translated into a specific probiotic therapy to break the cycle of re-infection. We characterised the nasopharyngeal microbiome of these children (controls) in comparison to children with rAOM (cases) to identify potentially protective bacteria. As some children with rAOM do not appear to carry any of the known otopathogens, we also hypothesised that characterisation of the middle ear microbiome could identify novel otopathogens, which may also guide the development of more effective therapies. RESULTS: Middle ear fluids, middle ear rinses and ear canal swabs from the cases and nasopharyngeal swabs from both groups underwent 16S rRNA gene sequencing. The nasopharyngeal microbiomes of cases and controls were distinct. We observed a significantly higher abundance of Corynebacterium and Dolosigranulum in the nasopharynx of controls. Alloiococcus, Staphylococcus and Turicella were abundant in the middle ear and ear canal of cases, but were uncommon in the nasopharynx of both groups. Gemella and Neisseria were characteristic of the case nasopharynx, but were not prevalent in the middle ear. CONCLUSIONS: Corynebacterium and Dolosigranulum are characteristic of a healthy nasopharyngeal microbiome. Alloiococcus, Staphylococcus and Turicella are possible novel otopathogens, though their rarity in the nasopharynx and prevalence in the ear canal means that their role as normal aural flora cannot be ruled out. Gemella and Neisseria are unlikely to be novel otopathogens as they do not appear to colonise the middle ear in children with rAOM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12866-018-1154-3) contains supplementary material, which is available to authorized users.",2018 Feb 20,"['Lappan, Rachael', 'Imbrogno, Kara', 'Sikazwe, Chisha', 'Anderson, Denise', 'Mok, Danny', 'Coates, Harvey', 'Vijayasekaran, Shyan', 'Bumbak, Paul', 'Blyth, Christopher C.', 'Jamieson, Sarra E.', 'Peacock, Christopher S.']",BMC Microbiol,,,False
426f916f89b03b6e4344774e7112741a1b304a35,PMC,A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera,http://dx.doi.org/10.1186/s12866-018-1154-3,PMC5819196,29458340,CC BY,"BACKGROUND: Recurrent acute otitis media (rAOM, recurrent ear infection) is a common childhood disease caused by bacteria termed otopathogens, for which current treatments have limited effectiveness. Generic probiotic therapies have shown promise, but seem to lack specificity. We hypothesised that healthy children with no history of AOM carry protective commensal bacteria that could be translated into a specific probiotic therapy to break the cycle of re-infection. We characterised the nasopharyngeal microbiome of these children (controls) in comparison to children with rAOM (cases) to identify potentially protective bacteria. As some children with rAOM do not appear to carry any of the known otopathogens, we also hypothesised that characterisation of the middle ear microbiome could identify novel otopathogens, which may also guide the development of more effective therapies. RESULTS: Middle ear fluids, middle ear rinses and ear canal swabs from the cases and nasopharyngeal swabs from both groups underwent 16S rRNA gene sequencing. The nasopharyngeal microbiomes of cases and controls were distinct. We observed a significantly higher abundance of Corynebacterium and Dolosigranulum in the nasopharynx of controls. Alloiococcus, Staphylococcus and Turicella were abundant in the middle ear and ear canal of cases, but were uncommon in the nasopharynx of both groups. Gemella and Neisseria were characteristic of the case nasopharynx, but were not prevalent in the middle ear. CONCLUSIONS: Corynebacterium and Dolosigranulum are characteristic of a healthy nasopharyngeal microbiome. Alloiococcus, Staphylococcus and Turicella are possible novel otopathogens, though their rarity in the nasopharynx and prevalence in the ear canal means that their role as normal aural flora cannot be ruled out. Gemella and Neisseria are unlikely to be novel otopathogens as they do not appear to colonise the middle ear in children with rAOM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12866-018-1154-3) contains supplementary material, which is available to authorized users.",2018 Feb 20,"['Lappan, Rachael', 'Imbrogno, Kara', 'Sikazwe, Chisha', 'Anderson, Denise', 'Mok, Danny', 'Coates, Harvey', 'Vijayasekaran, Shyan', 'Bumbak, Paul', 'Blyth, Christopher C.', 'Jamieson, Sarra E.', 'Peacock, Christopher S.']",BMC Microbiol,,,False
1ca739eaf0d43763f29e9b3615c90ca4a27120ba,PMC,A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera,http://dx.doi.org/10.1186/s12866-018-1154-3,PMC5819196,29458340,CC BY,"BACKGROUND: Recurrent acute otitis media (rAOM, recurrent ear infection) is a common childhood disease caused by bacteria termed otopathogens, for which current treatments have limited effectiveness. Generic probiotic therapies have shown promise, but seem to lack specificity. We hypothesised that healthy children with no history of AOM carry protective commensal bacteria that could be translated into a specific probiotic therapy to break the cycle of re-infection. We characterised the nasopharyngeal microbiome of these children (controls) in comparison to children with rAOM (cases) to identify potentially protective bacteria. As some children with rAOM do not appear to carry any of the known otopathogens, we also hypothesised that characterisation of the middle ear microbiome could identify novel otopathogens, which may also guide the development of more effective therapies. RESULTS: Middle ear fluids, middle ear rinses and ear canal swabs from the cases and nasopharyngeal swabs from both groups underwent 16S rRNA gene sequencing. The nasopharyngeal microbiomes of cases and controls were distinct. We observed a significantly higher abundance of Corynebacterium and Dolosigranulum in the nasopharynx of controls. Alloiococcus, Staphylococcus and Turicella were abundant in the middle ear and ear canal of cases, but were uncommon in the nasopharynx of both groups. Gemella and Neisseria were characteristic of the case nasopharynx, but were not prevalent in the middle ear. CONCLUSIONS: Corynebacterium and Dolosigranulum are characteristic of a healthy nasopharyngeal microbiome. Alloiococcus, Staphylococcus and Turicella are possible novel otopathogens, though their rarity in the nasopharynx and prevalence in the ear canal means that their role as normal aural flora cannot be ruled out. Gemella and Neisseria are unlikely to be novel otopathogens as they do not appear to colonise the middle ear in children with rAOM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12866-018-1154-3) contains supplementary material, which is available to authorized users.",2018 Feb 20,"['Lappan, Rachael', 'Imbrogno, Kara', 'Sikazwe, Chisha', 'Anderson, Denise', 'Mok, Danny', 'Coates, Harvey', 'Vijayasekaran, Shyan', 'Bumbak, Paul', 'Blyth, Christopher C.', 'Jamieson, Sarra E.', 'Peacock, Christopher S.']",BMC Microbiol,,,False
0cfbd799dde9aedd35ace107455d6b0bee8fa640,PMC,A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera,http://dx.doi.org/10.1186/s12866-018-1154-3,PMC5819196,29458340,CC BY,"BACKGROUND: Recurrent acute otitis media (rAOM, recurrent ear infection) is a common childhood disease caused by bacteria termed otopathogens, for which current treatments have limited effectiveness. Generic probiotic therapies have shown promise, but seem to lack specificity. We hypothesised that healthy children with no history of AOM carry protective commensal bacteria that could be translated into a specific probiotic therapy to break the cycle of re-infection. We characterised the nasopharyngeal microbiome of these children (controls) in comparison to children with rAOM (cases) to identify potentially protective bacteria. As some children with rAOM do not appear to carry any of the known otopathogens, we also hypothesised that characterisation of the middle ear microbiome could identify novel otopathogens, which may also guide the development of more effective therapies. RESULTS: Middle ear fluids, middle ear rinses and ear canal swabs from the cases and nasopharyngeal swabs from both groups underwent 16S rRNA gene sequencing. The nasopharyngeal microbiomes of cases and controls were distinct. We observed a significantly higher abundance of Corynebacterium and Dolosigranulum in the nasopharynx of controls. Alloiococcus, Staphylococcus and Turicella were abundant in the middle ear and ear canal of cases, but were uncommon in the nasopharynx of both groups. Gemella and Neisseria were characteristic of the case nasopharynx, but were not prevalent in the middle ear. CONCLUSIONS: Corynebacterium and Dolosigranulum are characteristic of a healthy nasopharyngeal microbiome. Alloiococcus, Staphylococcus and Turicella are possible novel otopathogens, though their rarity in the nasopharynx and prevalence in the ear canal means that their role as normal aural flora cannot be ruled out. Gemella and Neisseria are unlikely to be novel otopathogens as they do not appear to colonise the middle ear in children with rAOM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12866-018-1154-3) contains supplementary material, which is available to authorized users.",2018 Feb 20,"['Lappan, Rachael', 'Imbrogno, Kara', 'Sikazwe, Chisha', 'Anderson, Denise', 'Mok, Danny', 'Coates, Harvey', 'Vijayasekaran, Shyan', 'Bumbak, Paul', 'Blyth, Christopher C.', 'Jamieson, Sarra E.', 'Peacock, Christopher S.']",BMC Microbiol,,,True
69b7df3f6f4dd18c96e2d6b064e7ee3190cd54d0,PMC,Epidemiological characteristics of human-infective RNA viruses,http://dx.doi.org/10.1038/sdata.2018.17,PMC5819479,29461515,CC BY,"RNA viruses are a major threat to human health. Here, based on extensive literature searches carried out over a period of 18 years, we provide a catalogue of all 214 known human-infective RNA virus species. We link these viruses to metadata for a number of traits that influence their epidemiology, including the date of the first report of human infection, transmissibility in human populations, transmission route(s) and host range. This database can be used in comparative studies of human-infective RNA viruses to identify the characteristics of viruses most likely to pose the greatest public health threat, both now and in the future.",2018 Feb 20,"['Woolhouse, Mark E. J.', 'Brierley, Liam']",Sci Data,,,True
ccde33bdca9b5c7f879f105a4596e5b1ad3f9408,PMC,Longitudinal study of age-specific pattern of coronavirus infection in Lyle’s flying fox (Pteropus lylei) in Thailand,http://dx.doi.org/10.1186/s12985-018-0950-6,PMC5819653,29463282,CC BY,"BACKGROUND: Bats are natural reservoirs for several highly pathogenic and novel viruses including coronaviruses (CoVs) (mainly Alphacoronavirus and Betacoronavirus). Lyle’s flying fox (Pteropus lylei)‘s roosts and foraging sites are usually in the proximity to humans and animals. Knowledge about age-specific pattern of CoV infection in P. lylei, prevalence, and viral shedding at roosts and foraging sites may have an impact on infection-age-structure model to control CoV outbreak. METHODS: P. lylei bats were captured monthly during January–December 2012 for detection of CoV at three areas in Chonburi province; two human dwellings, S1 and S2, where few fruit trees were located with an open pig farm, 0.6 km and 5.5 km away from the bat roost, S3. Nested RT-PCR of RNA-dependent RNA polymerase (RdRp) gene from rectal swabs was used for CoV detection. The strain of CoV was confirmed by sequencing and phylogenetic analysis. RESULTS: CoV infection was found in both juveniles and adult bats between May and October (January, in adults only and April, in juveniles only). Of total rectal swab positives (68/367, 18.5%), ratio was higher in bats captured at S1 (11/44, 25.0%) and S2 (35/99, 35.4%) foraging sites than at roost (S3) (22/224, 9.8%). Juveniles (forearm length ≤ 136 mm) were found with more CoV infection than adults at all three sites; S1 (9/24, 37.5% vs 2/20, 10%), S2 (22/49, 44.9% vs 13/50, 26.0%), and S3 (10/30, 33.3% vs 12/194, 6.2%). The average BCI of CoV infected bats was significantly lower than uninfected bats. No gender difference related to infection was found at the sites. Phylogenetic analysis of conserved RdRp gene revealed that the detected CoVs belonged to group D betacoronavirus (n = 64) and alphacoronavirus (n = 4). CONCLUSIONS: The fact that CoV infection and shedding was found in more juvenile than adult bats may suggest transmission from mother during peripartum period. Whether viral reactivation during parturition period or stress is responsible in maintaining transmission in the bat colony needs to be explored.",2018 Feb 20,"['Wacharapluesadee, Supaporn', 'Duengkae, Prateep', 'Chaiyes, Aingorn', 'Kaewpom, Thongchai', 'Rodpan, Apaporn', 'Yingsakmongkon, Sangchai', 'Petcharat, Sininat', 'Phengsakul, Patcharakiti', 'Maneeorn, Pattarapol', 'Hemachudha, Thiravat']",Virol J,,,True
5b8be7d97df4b06c42eedda3d997677d60100828,PMC,The Host Restriction Factor Interferon-Inducible Transmembrane Protein 3 Inhibits Vaccinia Virus Infection,http://dx.doi.org/10.3389/fimmu.2018.00228,PMC5820317,29503647,CC BY,"Interferons (IFNs) establish dynamic host defense mechanisms by inducing various IFN-stimulated genes that encodes many antiviral innate immune effectors. IFN-inducible transmembrane (IFITM) proteins have been identified as intrinsic antiviral effectors, which block the entry of a broad spectrum of enveloped RNA viruses by interrupting virus-endosomal fusion. However, antiviral activity of IFITM proteins against mammalian DNA virus has not been demonstrated till date. Here, we sought to investigate the antiviral activities and mechanisms of interferon-inducible transmembrane protein 3 (IFITM3) protein against poxvirus infection. Analysis of expression kinetics of cell endogenous IFITM3 protein indicated that vaccinia virus (VACV) infection suppressed its translation, which was independent of IRF3 phosphorylation triggered by VACV. Although silencing of endogenous IFITM proteins did not affect their baseline antiviral effects in the cell, it has reduced the IFN-α-mediated inhibition of VACV infection, and also modulated VACV-induced cell death. Moreover, we discovered that overexpression of IFITM3 significantly restricted VACV infection, replication and proliferation mainly by interfering with virus entry processes prior to the virus nucleocapsid entry into the cytoplasm. Interestingly, IFITM3 overexpression showed an impact on virus binding. Furthermore, IFITM3 interfered with the cytosolic entry of virus through low pH-dependent fashion. Taken together, our findings provide the first evidence of exogenously expressed IFITM3 protein restricting infection of an enveloped DNA virus, thus expanding their antiviral spectrum. This study further explores the complex mechanism and provides novel insights into the interaction between virus infection and host defense.",2018 Feb 16,"['Li, Chang', 'Du, Shouwen', 'Tian, Mingyao', 'Wang, Yuhang', 'Bai, Jieying', 'Tan, Peng', 'Liu, Wei', 'Yin, Ronglan', 'Wang, Maopeng', 'Jiang, Ying', 'Li, Yi', 'Zhu, Na', 'Zhu, Yilong', 'Li, Tiyuan', 'Wu, Shipin', 'Jin, Ningyi', 'He, Fuchu']",Front Immunol,,,True
c1431d7d5f795acaa4781ae85a6b7c6d51cb54ed,PMC,"Human bocavirus and human metapneumovirus in hospitalized children with lower respiratory tract illness in Changsha, China",http://dx.doi.org/10.1111/irv.12535,PMC5820417,29266860,CC BY,"BACKGROUND: Lower respiratory tract illness is a major cause of morbidity and mortality in children worldwide, however, information about the epidemiological and clinical characteristics of LRTIs caused by HMPV and HBoV in China is limited. OBJECTIVES: Human bocavirus (HBoV) and human metapneumovirus (HMPV) are two important viruses for children with lower respiratory tract infections (LRTI). We aimed to assay the correlation between viral load and clinical characteristics of HBoV and HMPV with LRTI in Changsha, China. METHODS: Nasopharyngeal aspirates (NPAs) from children with LRTI were collected. Real‐time PCR was used to screen HBoV and HMPV. Analyses were performed using SPSS 16.0 software. RESULTS: Pneumonia was the most frequent diagnosis. There was no significant difference between HBoV‐ and HMPV‐positive patients in age (P = .506) or hospitalization duration (P = .280); 24.1% and 18.2% were positive for HBoV and HMPV. HBoV infections peaked in summer (32.2%), and HMPV infections peaked in winter (28.9%). The HBoV‐positive patients had a shorter hospitalization duration than the HBoV‐negative patients (P = .021), and the HMPV‐positive patients had a higher prevalence of fever than the HMPV‐negative patients (P = .002). The HBoV viral load was significantly higher among patients aged <1 year (P = .006). The mean HBoV and HMPV viral loads were not significantly different between patients with single infections and coinfections. Patients infected with HBoV only were older than those coinfected with HBoV and other respiratory viruses (P = .005). No significant difference was found in the clinical characteristics of patients infected with HMPV only and those coinfected with HMPV and other respiratory viruses. CONCLUSION: Pneumonia was the most frequent diagnosis caused by HBoV and HMPV. Neither HBoV nor HMPV viral load was correlated with disease severity.",2018 Mar 11,"['Zhou, Jie‐ying', 'Peng, Ying', 'Peng, Xiao‐you', 'Gao, Han‐chun', 'Sun, Ya‐ping', 'Xie, Le‐yun', 'Zhong, Li‐li', 'Duan, Zhao‐jun', 'Xie, Zhi‐ping', 'Cao, You‐de']",Influenza Other Respir Viruses,,,True
edfe02a438fa9b667313da8f03614303fc2a4a14,PMC,Species‐specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults,http://dx.doi.org/10.1111/irv.12538,PMC5820427,29350887,CC BY,"Human coronavirus (HCoV) is a known cause of influenza‐like illness (ILI). In a multisite, observational, longitudinal study of ILI among otherwise healthy adolescents and adults, 12% of subjects were PCR‐positive for HCoV. The distribution of species was as follows: HCoV‐OC43 (34%), HCoV‐229E (28%), HCoV‐NL63 (22%), and HCoV‐HKU1 (16%). We did not observe species‐specific differences in the clinical characteristics of HCoV infection, with the exception of HCoV‐HKU1, for which the severity of gastrointestinal symptoms trended higher on the fourth day of illness.",2018 Mar 2,"['Bouvier, Monique', 'Chen, Wei‐Ju', 'Arnold, John C.', 'Fairchok, Mary P.', 'Danaher, Patrick J.', 'Lalani, Tahaniyat', 'Malone, Leslie', 'Mor, Deepika', 'Ridoré, Michelande', 'Burgess, Timothy H.', 'Millar, Eugene V.']",Influenza Other Respir Viruses,,,True
731076fd240ebb00a9faf96ca9cedd40fb5fa50c,PMC,Incorporating health workers’ perspectives into a WHO guideline on personal protective equipment developed during an Ebola virus disease outbreak,http://dx.doi.org/10.12688/f1000research.12922.2,PMC5820616,29527297,CC BY,"Background: Ebola virus disease (EVD) health facility transmission can result in infection and death of health workers. The World Health Organization (WHO) supports countries in preparing for and responding to public health emergencies, which often require developing new guidance in short timelines with scarce evidence. The objective of this study was to understand frontline physicians’ and nurses’ perspectives about personal protective equipment (PPE) use during the 2014-2016 EVD outbreak in West Africa and to incorporate these findings into the development process of a WHO rapid advice guideline. Methods : We surveyed frontline physicians and nurses deployed to West Africa between March and September of 2014. Results: We developed the protocol, obtained ethics approval, delivered the survey, analysed the data and presented the findings as part of the evidence-to-decision tables at the expert panel meeting where the recommendations were formulated within eight weeks. Forty-four physicians and nurses responded to the survey. They generally felt at low or extremely low risk of virus transmission with all types of PPE used. Eye protection reduced the ability to provide care, mainly due to impaired visibility because of fogging. Heat and dehydration were a major issue for 76% of the participants using goggles and for 64% using a hood. Both gowns and coveralls were associated with significant heat stress and dehydration. Most participants (59%) were very confident that they were using PPE correctly. Conclusion : Our study demonstrated that it was possible to incorporate primary data on end-users’ preferences into a rapid advice guideline for a public health emergency in difficult field conditions. Health workers perceived a balance between transmission protection and ability to care for patients effectively while wearing PPE. These findings were used by the guideline development expert panel to formulate WHO recommendations on PPE for frontline providers caring for EVD patients in outbreak conditions.",2018 Mar 9,"['Den Boon, Saskia', 'Vallenas, Constanza', 'Ferri, Mauricio', 'Norris, Susan L.']",F1000Res,,,True
9f88c05ff539e0fd17ef61d08a51757f1e93b55a,PMC,Bacterial Pathogen Emergence Requires More than Direct Contact with a Novel Passerine Host,http://dx.doi.org/10.1128/IAI.00863-17,PMC5820954,29311238,CC BY,"While direct contact may sometimes be sufficient to allow a pathogen to jump into a new host species, in other cases, fortuitously adaptive mutations that arise in the original donor host are also necessary. Viruses have been the focus of most host shift studies, so less is known about the importance of ecological versus evolutionary processes to successful bacterial host shifts. Here we tested whether direct contact with the novel host was sufficient to enable the mid-1990s jump of the bacterium Mycoplasma gallisepticum from domestic poultry to house finches (Haemorhous mexicanus). We experimentally inoculated house finches with two genetically distinct M. gallisepticum strains obtained either from poultry (Rlow) or from house finches (HF1995) during an epizootic outbreak. All 15 house finches inoculated with HF1995 became infected, whereas Rlow successfully infected 12 of 15 (80%) inoculated house finches. Comparisons among infected birds showed that, relative to HF1995, Rlow achieved substantially lower bacterial loads in the host respiratory mucosa and was cleared faster. Furthermore, Rlow-infected finches were less likely to develop clinical symptoms than HF1995-infected birds and, when they did, displayed milder conjunctivitis. The lower infection success of Rlow relative to HF1995 was not, however, due to a heightened host antibody response to Rlow. Taken together, our results indicate that contact between infected poultry and house finches was not, by itself, sufficient to explain the jump of M. gallisepticum to house finches. Instead, mutations arising in the original poultry host would have been necessary for successful pathogen emergence in the novel finch host.",2018 Feb 20,"['Staley, Molly', 'Hill, Geoffrey E.', 'Josefson, Chloe C.', 'Armbruster, Jonathan W.', 'Bonneaud, Camille']",Infect Immun,,,True
b7240857da81a0bee7cfb964a7e838f7f1120b46,PMC,Hemagglutinin-specific neutralization of subacute sclerosing panencephalitis viruses,http://dx.doi.org/10.1371/journal.pone.0192245,PMC5821319,29466428,CC BY,"Subacute sclerosing panencephalitis (SSPE) is a progressive, lethal complication of measles caused by particular mutants of measles virus (MeV) that persist in the brain despite high levels of neutralizing antibodies. We addressed the hypothesis that antigenic drift is involved in the pathogenetic mechanism of SSPE by analyzing antigenic alterations in the MeV envelope hemagglutinin protein (MeV-H) found in patients with SSPE in relation to major circulating MeV genotypes. To this aim, we obtained cDNA for the MeV-H gene from tissue taken at brain autopsy from 3 deceased persons with SSPE who had short (3–4 months, SMa79), average (3.5 years, SMa84), and long (18 years, SMa94) disease courses. Recombinant MeVs with a substituted MeV-H gene were generated by a reverse genetic system. Virus neutralization assays with a panel of anti-MeV-H murine monoclonal antibodies (mAbs) or vaccine-immunized mouse anti-MeV-H polyclonal sera were performed to determine the antigenic relatedness. Functional and receptor-binding analysis of the SSPE MeV-H showed activity in a SLAM/nectin-4–dependent manner. Similar to our panel of wild-type viruses, our SSPE viruses showed an altered antigenic profile. Genotypes A, G3, and F (SSPE case SMa79) were the exception, with an intact antigenic structure. Genotypes D7 and F (SSPE SMa79) showed enhanced neutralization by mAbs targeting antigenic site IIa. Genotypes H1 and the recently reported D4.2 were the most antigenically altered genotypes. Epitope mapping of neutralizing mAbs BH015 and BH130 reveal a new antigenic site on MeV-H, which we designated Φ for its intermediate position between previously defined antigenic sites Ia and Ib. We conclude that SSPE-causing viruses show similar antigenic properties to currently circulating MeV genotypes. The absence of a direct correlation between antigenic changes and predisposition of a certain genotype to cause SSPE does not lend support to the proposed antigenic drift as a pathogenetic mechanism in SSPE.",2018 Feb 21,"['Muñoz-Alía, Miguel Ángel', 'Muller, Claude P.', 'Russell, Stephen J.']",PLoS One,,,True
014336e4855d194c1833ba91c8ae3b302cbeafe2,PMC,Protective effects and immunomodulation on piglets infected with rotavirus following resveratrol supplementation,http://dx.doi.org/10.1371/journal.pone.0192692,PMC5821335,29466421,CC BY,"Rotavirus (RV), belonging to Reoviridae family, is the leading cause of acute severe viral diarrhea in children (under 5 years old) and infant animals worldwide. Although vaccines are commonly used to prevent infection, episodes of diarrhea caused by RV frequently occur. Thus, this study was conducted to determine whether resveratrol had protective effects against RV infection in piglets. Following pretreatment with resveratrol dry suspension through adding into the basal diet for 3 weeks, the piglets were orally challenged with RV. We found that resveratrol could alleviate diarrhea induced by RV infection. Resveratrol-treatment inhibited the TNF-α production, indicating that the anti-RV activity of resveratrol may be achieved by reducing the inflammatory response. The IFN-γ level was elevated in 10mg/kg/d resveratrol-treated group and 30mg/kg/d resveratrol-treated group after RV infection. The ratios of CD4+/CD8+ in resveratrol-treated groups were the same as that in mock infected group, suggesting that resveratrol could maintain the immune function in RV-infected piglets. It was found that resveratrol could alleviate diarrhea induced by RV infection. These results revealed that resveratrol dry suspension could be a new control measure for RV infection.",2018 Feb 21,"['Cui, Qiankun', 'Fu, Qiuting', 'Zhao, Xinghong', 'Song, Xu', 'Yu, Jiankang', 'Yang, Yi', 'Sun, Kai', 'Bai, Lu', 'Tian, Ye', 'Chen, Shufan', 'Jia, Renyong', 'Zou, Yuanfeng', 'Li, Lixia', 'Liang, Xiaoxia', 'He, Changliang', 'Yin, Lizi', 'Ye, Gang', 'Lv, Cheng', 'Yue, Guizhou', 'Yin, Zhongqiong']",PLoS One,,,True
d62945f450e20fa12213b58d43cd1d0348de2e5b,PMC,When are pathogen genome sequences informative of transmission events?,http://dx.doi.org/10.1371/journal.ppat.1006885,PMC5821398,29420641,CC BY,"Recent years have seen the development of numerous methodologies for reconstructing transmission trees in infectious disease outbreaks from densely sampled whole genome sequence data. However, a fundamental and as of yet poorly addressed limitation of such approaches is the requirement for genetic diversity to arise on epidemiological timescales. Specifically, the position of infected individuals in a transmission tree can only be resolved by genetic data if mutations have accumulated between the sampled pathogen genomes. To quantify and compare the useful genetic diversity expected from genetic data in different pathogen outbreaks, we introduce here the concept of ‘transmission divergence’, defined as the number of mutations separating whole genome sequences sampled from transmission pairs. Using parameter values obtained by literature review, we simulate outbreak scenarios alongside sequence evolution using two models described in the literature to describe transmission divergence of ten major outbreak-causing pathogens. We find that while mean values vary significantly between the pathogens considered, their transmission divergence is generally very low, with many outbreaks characterised by large numbers of genetically identical transmission pairs. We describe the impact of transmission divergence on our ability to reconstruct outbreaks using two outbreak reconstruction tools, the R packages outbreaker and phybreak, and demonstrate that, in agreement with previous observations, genetic sequence data of rapidly evolving pathogens such as RNA viruses can provide valuable information on individual transmission events. Conversely, sequence data of pathogens with lower mean transmission divergence, including Streptococcus pneumoniae, Shigella sonnei and Clostridium difficile, provide little to no information about individual transmission events. Our results highlight the informational limitations of genetic sequence data in certain outbreak scenarios, and demonstrate the need to expand the toolkit of outbreak reconstruction tools to integrate other types of epidemiological data.",2018 Feb 8,"['Campbell, Finlay', 'Strang, Camilla', 'Ferguson, Neil', 'Cori, Anne', 'Jombart, Thibaut']",PLoS Pathog,,,True
d84ac9fd44932276ccfa7da5add9776e7d56595a,PMC,Pentraxin 3 deficiency enhances features of chronic rejection in a mouse orthotopic lung transplantation model,http://dx.doi.org/10.18632/oncotarget.23902,PMC5823599,29492210,CC BY,"Chronic lung allograft dysfunction (CLAD) is a serious complication after lung transplantation and thought to represent chronic rejection. Increased expression of Pentraxin 3 (PTX3), an acute phase protein, was associated with worse outcome in lung transplant patients. To determine the role of recipient PTX3 in development of chronic rejection, we used a minor alloantigen-mismatched murine orthotopic single lung transplant model. Male C57BL/10 mice were used as donors. Male PTX3 knockout (KO) mice and their wild type (WT) littermates on 129/SvEv/C57BL6/J background were used as recipients. In KO recipients, 7/13 grafted lungs were consolidated without volume recovery on CT scan, while only 2/9 WT mice showed similar graft consolidation. For grafts where lung volume could be reliably analyzed by CT scan, the lung volume recovery was significantly reduced in KO mice compared to WT. Interstitial inflammation, parenchymal fibrosis and bronchiolitis obliterans scores were significantly higher in KO mice. Presence of myofibroblasts and lymphoid aggregation was significantly enhanced in the grafts of PTX3 KO recipients. Recipient PTX3 deficiency enhanced chronic rejection-like lesions by promoting a fibrotic process in the airways and lung parenchyma. The underlying mechanisms and potential protective role of exogenous PTX3 as a therapy should be further explored.",2018 Jan 3,"['Yoshida, Mitsuteru', 'Oishi, Hisashi', 'Martinu, Tereza', 'Hwang, David M.', 'Takizawa, Hiromitsu', 'Sugihara, Junichi', 'McKee, Trevor D.', 'Bai, Xiaohui', 'Guana, Zehong', 'Lua, Christina', 'Cho, Hae-Ra', 'Juvet, Stephen', 'Cypel, Marcelo', 'Keshavjee, Shaf', 'Liu, Mingyao']",Oncotarget,,,True
30dd2d16b15b90f248fc583a4e02d5c1c1aeb1ee,PMC,Pentraxin 3 deficiency enhances features of chronic rejection in a mouse orthotopic lung transplantation model,http://dx.doi.org/10.18632/oncotarget.23902,PMC5823599,29492210,CC BY,"Chronic lung allograft dysfunction (CLAD) is a serious complication after lung transplantation and thought to represent chronic rejection. Increased expression of Pentraxin 3 (PTX3), an acute phase protein, was associated with worse outcome in lung transplant patients. To determine the role of recipient PTX3 in development of chronic rejection, we used a minor alloantigen-mismatched murine orthotopic single lung transplant model. Male C57BL/10 mice were used as donors. Male PTX3 knockout (KO) mice and their wild type (WT) littermates on 129/SvEv/C57BL6/J background were used as recipients. In KO recipients, 7/13 grafted lungs were consolidated without volume recovery on CT scan, while only 2/9 WT mice showed similar graft consolidation. For grafts where lung volume could be reliably analyzed by CT scan, the lung volume recovery was significantly reduced in KO mice compared to WT. Interstitial inflammation, parenchymal fibrosis and bronchiolitis obliterans scores were significantly higher in KO mice. Presence of myofibroblasts and lymphoid aggregation was significantly enhanced in the grafts of PTX3 KO recipients. Recipient PTX3 deficiency enhanced chronic rejection-like lesions by promoting a fibrotic process in the airways and lung parenchyma. The underlying mechanisms and potential protective role of exogenous PTX3 as a therapy should be further explored.",2018 Jan 3,"['Yoshida, Mitsuteru', 'Oishi, Hisashi', 'Martinu, Tereza', 'Hwang, David M.', 'Takizawa, Hiromitsu', 'Sugihara, Junichi', 'McKee, Trevor D.', 'Bai, Xiaohui', 'Guana, Zehong', 'Lua, Christina', 'Cho, Hae-Ra', 'Juvet, Stephen', 'Cypel, Marcelo', 'Keshavjee, Shaf', 'Liu, Mingyao']",Oncotarget,,,False
eb412f70e3deca0ce80e6ff070fb80a31aff71a0,PMC,Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain,http://dx.doi.org/10.1038/s41598-018-21799-8,PMC5823904,29472575,CC BY,"Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) inhibitors induces strong antihyperalgesic effect during inflammatory pain. In this study we observed low level of DPP4 mRNA in the rat spinal dorsal horn in physiological conditions, which did not change significantly either in carrageenan-induced inflammatory or partial nerve ligation-generated neuropathic states. In naïve animals, microglia and astrocytes expressed DPP4 protein with one and two orders of magnitude higher than neurons, respectively. DPP4 significantly increased in astrocytes during inflammation and in microglia in neuropathy. Intrathecal application of two DPP4 inhibitors tripeptide isoleucin-prolin-isoleucin (IPI) and the antidiabetic drug vildagliptin resulted in robust opioid-dependent antihyperalgesic effect during inflammation, and milder but significant opioid-independent antihyperalgesic action in the neuropathic model. The opioid-mediated antihyperalgesic effect of IPI was exclusively related to mu-opioid receptors, while vildagliptin affected mainly delta-receptor activity, although mu- and kappa-receptors were also involved. None of the inhibitors influenced allodynia. Our results suggest pathology and glia-type specific changes of DPP4 activity in the spinal cord, which contribute to the development and maintenance of hyperalgesia and interact with endogenous opioid systems.",2018 Feb 22,"['Király, Kornél', 'Kozsurek, Márk', 'Lukácsi, Erika', 'Barta, Benjamin', 'Alpár, Alán', 'Balázsa, Tamás', 'Fekete, Csaba', 'Szabon, Judit', 'Helyes, Zsuzsanna', 'Bölcskei, Kata', 'Tékus, Valéria', 'Tóth, Zsuzsanna E.', 'Pap, Károly', 'Gerber, Gábor', 'Puskár, Zita']",Sci Rep,,,False
88d9d333b7b85d34405f27fc2e469cad48a1f8c4,PMC,Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain,http://dx.doi.org/10.1038/s41598-018-21799-8,PMC5823904,29472575,CC BY,"Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) inhibitors induces strong antihyperalgesic effect during inflammatory pain. In this study we observed low level of DPP4 mRNA in the rat spinal dorsal horn in physiological conditions, which did not change significantly either in carrageenan-induced inflammatory or partial nerve ligation-generated neuropathic states. In naïve animals, microglia and astrocytes expressed DPP4 protein with one and two orders of magnitude higher than neurons, respectively. DPP4 significantly increased in astrocytes during inflammation and in microglia in neuropathy. Intrathecal application of two DPP4 inhibitors tripeptide isoleucin-prolin-isoleucin (IPI) and the antidiabetic drug vildagliptin resulted in robust opioid-dependent antihyperalgesic effect during inflammation, and milder but significant opioid-independent antihyperalgesic action in the neuropathic model. The opioid-mediated antihyperalgesic effect of IPI was exclusively related to mu-opioid receptors, while vildagliptin affected mainly delta-receptor activity, although mu- and kappa-receptors were also involved. None of the inhibitors influenced allodynia. Our results suggest pathology and glia-type specific changes of DPP4 activity in the spinal cord, which contribute to the development and maintenance of hyperalgesia and interact with endogenous opioid systems.",2018 Feb 22,"['Király, Kornél', 'Kozsurek, Márk', 'Lukácsi, Erika', 'Barta, Benjamin', 'Alpár, Alán', 'Balázsa, Tamás', 'Fekete, Csaba', 'Szabon, Judit', 'Helyes, Zsuzsanna', 'Bölcskei, Kata', 'Tékus, Valéria', 'Tóth, Zsuzsanna E.', 'Pap, Károly', 'Gerber, Gábor', 'Puskár, Zita']",Sci Rep,,,True
693a08804a5da83a38bff8f67201eb50817e557e,PMC,Identification of a novel compound targeting the nuclear export of influenza A virus nucleoprotein,http://dx.doi.org/10.1111/jcmm.13467,PMC5824420,29193684,CC BY,"Although antiviral drugs are available for the treatment of influenza infection, it is an urgent requirement to develop new antiviral drugs regarding the emergence of drug‐resistant viruses. The nucleoprotein (NP) is conserved among all influenza A viruses (IAVs) and has no cellular equivalent. Therefore, NP is an ideal target for the development of new IAV inhibitors. In this study, we identified a novel anti‐influenza compound, ZBMD‐1, from a library of 20,000 compounds using cell‐based influenza A infection assays. We found that ZBMD‐1 inhibited the replication of H1N1 and H3N2 influenza A virus strains in vitro, with an IC (50) ranging from 0.41–1.14 μM. Furthermore, ZBMD‐1 inhibited the polymerase activity and specifically impaired the nuclear export of NP. Further investigation indicated that ZBMD‐1 binds to the nuclear export signal 3 (NES3) domain and the dimer interface of the NP pocket. ZBMD‐1 also protected mice that were challenged with lethal doses of A/PR/8/1934 (H1N1) virus, effectively relieving lung histopathology changes, as well as strongly inhibiting the expression of pro‐inflammatory cytokines/chemokines, without inducing toxicity effects in mice. These results suggest that ZBMD‐1 is a promising anti‐influenza compound which can be further investigated as a useful strategy against IAVs in the future.",2018 Mar 30,"['Huang, Feng', 'Chen, Jingliang', 'Zhang, Junsong', 'Tan, Likai', 'Lu, Gui', 'Luo, Yongjie', 'Pan, Ting', 'Liang, Juanran', 'Li, Qianwen', 'Luo, Baohong', 'Zhang, Hui', 'Lu, Gen']",J Cell Mol Med,,,True
a58e071a01535515949fdc00e6942e2e5ada7ad7,PMC,Canine caliciviruses of four serotypes from military and research dogs recovered in 1963−1978 belong to two phylogenetic clades in the Vesivirus genus,http://dx.doi.org/10.1186/s12985-018-0944-4,PMC5824495,29471848,CC BY,"BACKGROUND: Vesiviruses (family Caliciviridae) had been shown capable of invading a variety of host species, raising concern of their zoonotic potential. Since the 1980’s, several canine caliciviruses (CaCV) isolates have been reported and are phylogenetically related to the vesiviruses with features distinct from both Vesicular exanthema of swine virus (VESV) and Feline calicivirus (FCV) species in phylogeny, serology and cell culture specificities. Etiological studies of canine diseases in dogs used for military services and laboratory studies were conducted in 1963–1978 at the Walter Reed Army Institute of Research. Multiple known and unknown viral pathogens including caliciviruses were recovered. METHODS: Four unidentified isolates were recovered in Walter Reed Canine Cells (WRCC) from respiratory, fecal and penile specimens. Physicochemical tests, electron microscopy, viral cultivation in human and animal cells, antibody neutralization assays, and recently the genome sequencing were used to characterize the isolates. Sera from these dogs and their cohorts were tested with the isolates to determine origin and prevalence of the infections. RESULTS: The viral isolates were small non-enveloped spherical RNA virions, 27 to 42 nm in diameter with cup-like structures, indicating they are caliciviruses. They propagated in WRCC and MDCK cells, not in either other canine cells or human and other animal cells. Each isolate is antigenically distinct and react with dog sera in respective cohorts. The genomes have nucleotide identities ranging from 70.3% to 90.7% and encode the non-structural polyprotein (1810 amino acids), major capsid protein (691 amino acids) and minor structural protein (134 amino acids). They belong to two different phylogenetic clades in Vesivirus genus with close relation with canine calicivirus (CaCV). CONCLUSIONS: These CaCV isolates have restricted cell tropism, antigenic diversity and genetic variation. Further investigation will shed light on antigenic relation to other vesiviruses, and its pathogenicity for dogs and potential infectivity to other animals. Together with the previously reported CaCV strains provides significant evidence to support the formation of a new CaCV species in the Vesivirus genus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-0944-4) contains supplementary material, which is available to authorized users.",2018 Feb 23,"['Binn, Leonard N.', 'Norby, Erica A.', 'Marchwicki, Ruth H.', 'Jarman, Richard G.', 'Keiser, Paul B.', 'Hang, Jun']",Virol J,,,True
1de438fe6e455f606c21b859df1769e2807c3546,PMC,Understanding nurses’ dual practice: a scoping review of what we know and what we still need to ask on nurses holding multiple jobs,http://dx.doi.org/10.1186/s12960-018-0276-x,PMC5824568,29471846,CC BY,"BACKGROUND: Mounting evidence suggests that holding multiple concurrent jobs in public and private (dual practice) is common among health workers in low- as well as high-income countries. Nurses are world’s largest health professional workforce and a critical resource for achieving Universal Health Coverage. Nonetheless, little is known about nurses’ engagement with dual practice. METHODS: We conducted a scoping review of the literature on nurses’ dual practice with the objective of generating hypotheses on its nature and consequences, and define a research agenda on the phenomenon. The Arksey and O’Malley’s methodological steps were followed to develop the research questions, identify relevant studies, include/exclude studies, extract the data, and report the findings. PRISMA guidelines were additionally used to conduct the review and report on results. RESULTS: Of the initial 194 records identified, a total of 35 met the inclusion criteria for nurses’ dual practice; the vast majority (65%) were peer-reviewed publications, followed by nursing magazine publications (19%), reports, and doctoral dissertations. Twenty publications focused on high-income countries, 16 on low- or middle-income ones, and two had a multi country perspective. Although holding multiple jobs not always amounted to dual practice, several ways were found for public-sector nurses to engage concomitantly in public and private employments, in regulated as well as in informal, casual fashions. Some of these forms were reported as particularly prevalent, from over 50% in Australia, Canada, and the UK, to 28% in South Africa. The opportunity to increase a meagre salary, but also a dissatisfaction with the main job and the flexibility offered by multiple job-holding arrangements, were among the reported reasons for engaging in these practices. DISCUSSION AND CONCLUSIONS: Limited and mostly circumstantial evidence exists on nurses’ dual practice, with the few existing studies suggesting that the phenomenon is likely to be very common and carry  implications for health systems and nurses’ welfare worldwide. We offer an agenda for future research to consolidate the existing evidence and to further explore nurses’ motivation; without a better understanding of nurse dual practice, this will continue to be a largely ‘hidden’ element in nursing workforce policy and practice, with an unclear impact on the delivery of care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12960-018-0276-x) contains supplementary material, which is available to authorized users.",2018 Feb 22,"['Russo, Giuliano', 'Fronteira, Inês', 'Jesus, Tiago Silva', 'Buchan, James']",Hum Resour Health,,,True
3053529090a8974edc1ad695d3be4d407eef9674,PMC,"Two predominant MUPs, OBP3 and MUP13, are male pheromones in rats",http://dx.doi.org/10.1186/s12983-018-0254-0,PMC5824612,29483934,CC BY,"BACKGROUND: In rats, urine-borne male pheromones comprise organic volatile compounds and major urinary proteins (MUPs). A number of volatile pheromones have been reported, but no MUP pheromones have been identified in rat urine. RESULTS: We used sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing electrophoresis (IEF), nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS) after in gel digestion of the proteins and quantitative real-time PCR (qRT-PCR) and showed that the levels of two MUPs, odorant-binding protein 3 (OBP3) (i.e. PGCL4) and MUP13 (i.e. PGCL1), in urine and their mRNAs in liver were higher in males than in females and were suppressed by orchidectomy and restored by testosterone treatment (T treatment). We then generated recombinant MUPs (rMUPs) and found that the sexual attractiveness of urine from castrated males to females significantly increased after the addition of either recombinant OBP3 (rOBP3) or recombinant MUP13 (rMUP13). Using c-Fos immunohistochemistry, we further examined neuronal activation in the brains of female rats after they sniffed rOBP3 or rMUP13. Both rOBP3 and rMUP13 activated the accessory olfactory bulb (AOB), medial preoptic area (MPA), bed nucleus of the stria terminalis (BST), medial amygdala (MeA), posteromedial cortical amygdala (PMCo) and ventromedial nucleus of the hypothalamus (VMH), which participate in the neural circuits responsible for pheromone-induced sexual behaviours. In particular, more c-Fos-immunopositive (c-Fos-ir) cells were observed in the posterior AOB than in the anterior AOB. CONCLUSIONS: The expression of OBP3 and MUP13 was male-biased and androgen-dependent. They attracted females and activated brain areas related to sexual behaviours in female rats, suggesting that both OBP3 and MUP13 are male pheromones in rats. Particularly, an OBP excreted into urine was exemplified to be a chemical signal.",2018 Feb 23,"['Guo, Xiao', 'Guo, Huifen', 'Zhao, Lei', 'Zhang, Yao-Hua', 'Zhang, Jian-Xu']",Front Zool,,,True
64fd6468ffce758ed2d0d198368d1a62fec821ca,PMC,Vps3 and Vps8 control integrin trafficking from early to recycling endosomes and regulate integrin-dependent functions,http://dx.doi.org/10.1038/s41467-018-03226-8,PMC5824891,29476049,CC BY,"Recycling endosomes maintain plasma membrane homeostasis and are important for cell polarity, migration, and cytokinesis. Yet, the molecular machineries that drive endocytic recycling remain largely unclear. The CORVET complex is a multi-subunit tether required for fusion between early endosomes. Here we show that the CORVET-specific subunits Vps3 and Vps8 also regulate vesicular transport from early to recycling endosomes. Vps3 and Vps8 localise to Rab4-positive recycling vesicles and co-localise with the CHEVI complex on Rab11-positive recycling endosomes. Depletion of Vps3 or Vps8 does not affect transferrin recycling, but delays the delivery of internalised integrins to recycling endosomes and their subsequent return to the plasma membrane. Consequently, Vps3/8 depletion results in defects in integrin-dependent cell adhesion and spreading, focal adhesion formation, and cell migration. These data reveal a role for Vps3 and Vps8 in a specialised recycling pathway important for integrin trafficking.",2018 Feb 23,"['Jonker, C. T. H.', 'Galmes, R.', 'Veenendaal, T.', 'ten Brink, C.', 'van der Welle, R. E. N.', 'Liv, N.', 'de Rooij, J.', 'Peden, A. A.', 'van der Sluijs, P.', 'Margadant, C.', 'Klumperman, J.']",Nat Commun,,,False
d3fd68b890e2f89c82196919d1623aed3b8d9408,PMC,Vps3 and Vps8 control integrin trafficking from early to recycling endosomes and regulate integrin-dependent functions,http://dx.doi.org/10.1038/s41467-018-03226-8,PMC5824891,29476049,CC BY,"Recycling endosomes maintain plasma membrane homeostasis and are important for cell polarity, migration, and cytokinesis. Yet, the molecular machineries that drive endocytic recycling remain largely unclear. The CORVET complex is a multi-subunit tether required for fusion between early endosomes. Here we show that the CORVET-specific subunits Vps3 and Vps8 also regulate vesicular transport from early to recycling endosomes. Vps3 and Vps8 localise to Rab4-positive recycling vesicles and co-localise with the CHEVI complex on Rab11-positive recycling endosomes. Depletion of Vps3 or Vps8 does not affect transferrin recycling, but delays the delivery of internalised integrins to recycling endosomes and their subsequent return to the plasma membrane. Consequently, Vps3/8 depletion results in defects in integrin-dependent cell adhesion and spreading, focal adhesion formation, and cell migration. These data reveal a role for Vps3 and Vps8 in a specialised recycling pathway important for integrin trafficking.",2018 Feb 23,"['Jonker, C. T. H.', 'Galmes, R.', 'Veenendaal, T.', 'ten Brink, C.', 'van der Welle, R. E. N.', 'Liv, N.', 'de Rooij, J.', 'Peden, A. A.', 'van der Sluijs, P.', 'Margadant, C.', 'Klumperman, J.']",Nat Commun,,,False
3041ba0d88fceebd32a14e0b62b443961a64a82b,PMC,Vps3 and Vps8 control integrin trafficking from early to recycling endosomes and regulate integrin-dependent functions,http://dx.doi.org/10.1038/s41467-018-03226-8,PMC5824891,29476049,CC BY,"Recycling endosomes maintain plasma membrane homeostasis and are important for cell polarity, migration, and cytokinesis. Yet, the molecular machineries that drive endocytic recycling remain largely unclear. The CORVET complex is a multi-subunit tether required for fusion between early endosomes. Here we show that the CORVET-specific subunits Vps3 and Vps8 also regulate vesicular transport from early to recycling endosomes. Vps3 and Vps8 localise to Rab4-positive recycling vesicles and co-localise with the CHEVI complex on Rab11-positive recycling endosomes. Depletion of Vps3 or Vps8 does not affect transferrin recycling, but delays the delivery of internalised integrins to recycling endosomes and their subsequent return to the plasma membrane. Consequently, Vps3/8 depletion results in defects in integrin-dependent cell adhesion and spreading, focal adhesion formation, and cell migration. These data reveal a role for Vps3 and Vps8 in a specialised recycling pathway important for integrin trafficking.",2018 Feb 23,"['Jonker, C. T. H.', 'Galmes, R.', 'Veenendaal, T.', 'ten Brink, C.', 'van der Welle, R. E. N.', 'Liv, N.', 'de Rooij, J.', 'Peden, A. A.', 'van der Sluijs, P.', 'Margadant, C.', 'Klumperman, J.']",Nat Commun,,,True
6ba9d2be64380669690c2e8a8a614100a7a5a50a,PMC,Development of improved therapeutic mesothelin-based vaccines for pancreatic cancer,http://dx.doi.org/10.1371/journal.pone.0193131,PMC5825036,29474384,CC BY,"Pancreatic cancer is the 5(th) leading cause of cancer deaths, and there are no effective treatments. We developed a poxvirus platform vaccine with improved immunogenicity and inserted the mesothelin gene to create an anti-mesothelin cancer vaccine. Mesothelin expression is mostly restricted to tumors in adult mammals and thus may be a good target for cancer treatment. We show here that the modified vaccinia virus Ankara (MVA) virus expressing mesothelin and the enhanced MVA virus missing the immunosuppressive A35 gene and expressing mesothelin were both safe in mice and were able to induce IFN-gamma secreting T cells in response to mesothelin expressing tumor cells. In addition, the MVA virus has oncolytic properties in vitro as it can replicate in and kill Panc02 pancreatic adenocarcinoma cell line tumor cells, even though it is unable to replicate in most mammalian cells. Deletion of the A35 gene in MVA improved T cell responses as expected. However, we were unable to demonstrate inhibition of Panc02 tumor growth in immunocompetent mice with pre-vaccination of mice, boosts, or even intratumoral injections of the recombinant viruses. Vaccine efficacy may be limited by shedding of mesothelin from tumor cells thus creating a protective screen from the immune system.",2018 Feb 23,"['White, Michael', 'Freistaedter, Andrew', 'Jones, Gwendolyn J. B.', 'Zervos, Emmanuel', 'Roper, Rachel L.']",PLoS One,,,True
7f2868688c3e1140f573628312738e2222fe5dfd,PMC,Lipidomic analysis of immune activation in equine leptospirosis and Leptospira-vaccinated horses,http://dx.doi.org/10.1371/journal.pone.0193424,PMC5825116,29474474,CC BY,"Currently available diagnostic assays for leptospirosis cannot differentiate vaccine from infection serum antibody. Several leptospiral proteins that are upregulated during infection have been described, but their utility as a diagnostic marker is still unclear. In this study, we undertook a lipidomics approach to determine if there are any differences in the serum lipid profiles of horses naturally infected with pathogenic Leptospira spp. and horses vaccinated against a commercially available bacterin. Utilizing a high-resolution mass spectrometry serum lipidomics analytical platform, we demonstrate that cyclic phosphatidic acids, diacylglycerols, and hydroperoxide oxidation products of choline plasmalogens are elevated in the serum of naturally infected as well as vaccinated horses. Other lipids of interest were triacylglycerols that were only elevated in the serum of infected horses and sphingomyelins that were increased only in the serum of vaccinated horses. This is the first report looking at the equine serum lipidome during leptospiral infection and vaccination.",2018 Feb 23,"['Wood, Paul L.', 'Steinman, Margaret', 'Erol, Erdal', 'Carter, Craig', 'Christmann, Undine', 'Verma, Ashutosh']",PLoS One,,,True
ecfcf1c18796bfdf5dfd83193448b5c2f9fbdb81,PMC,TBC2target: A Resource of Predicted Target Genes of Tea Bioactive Compounds,http://dx.doi.org/10.3389/fpls.2018.00211,PMC5827417,29520288,CC BY,"Tea is one of the most popular non-alcoholic beverages consumed worldwide. Numerous bioactive constituents of tea were confirmed to possess healthy benefits via the mechanisms of regulating gene expressions or protein activities. However, a complete interacting profile between tea bioactive compounds (TBCs) and their target genes is lacking, which put an obstacle in the study of healthy function of tea. To fill this gap, we developed a database of target genes of TBCs (TBC2target, http://camellia.ahau.edu.cn/TBC2target) based on a pharmacophore mapping approach. In TBC2target, 6,226 interactions between 240 TBCs and 673 target genes were documented. TBC2target contains detailed information about each interacting entry, such as TBC, CAS number, PubChem CID, source of compound (e.g., green, black), compound type, target gene(s) of TBC, gene symbol, gene ID, ENSEMBL ID, PDB ID, TBC bioactivity and the reference. Using the TBC-target associations, we constructed a bipartite network and provided users the global network and local sub-network visualization and topological analyses. The entire database is free for online browsing, searching and downloading. In addition, TBC2target provides a BLAST search function to facilitate use of the database. The particular strengths of TBC2target are the inclusion of the comprehensive TBC-target interactions, and the capacity to visualize and analyze the interacting networks, which may help uncovering the beneficial effects of tea on human health as a central resource in tea health community.",2018 Feb 22,"['Zhang, Shihua', 'Zhang, Liang', 'Wang, Yijun', 'Yang, Jian', 'Liao, Mingzhi', 'Bi, Shoudong', 'Xie, Zhongwen', 'Ho, Chi-Tang', 'Wan, Xiaochun']",Front Plant Sci,,,True
5df3884ac512e1ad4cedd33f5e83b09a9cfa5668,PMC,Intravenous immunoglobulin fails to improve ARDS in patients undergoing ECMO therapy,http://dx.doi.org/10.1186/s40560-018-0278-8,PMC5827994,29497534,CC BY,"BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with high mortality rates. ARDS patients suffer from severe hypoxemia, and extracorporeal membrane oxygenation (ECMO) therapy may be necessary to ensure oxygenation. ARDS has various etiologies, including trauma, ischemia-reperfusion injury or infections of various origins, and the associated immunological responses may vary. To support the immunological response in this patient collective, we used intravenous IgM immunoglobulin therapy to enhance the likelihood of pulmonary recovery. METHODS: ARDS patients admitted to the intensive care unit (ICU) who were placed on ECMO and treated with (IVIG group; n = 29) or without (control group; n = 28) intravenous IgM-enriched immunoglobulins for 3 days in the initial stages of ARDS were analyzed retrospectively. RESULTS: The baseline characteristics did not differ between the groups, although the IVIG group showed a significantly reduced oxygenation index compared to the control group. We found no differences in the length of ICU stay or ventilation parameters. We did not find a significant difference between the groups for the extent of inflammation or for overall survival. CONCLUSION: We conclude that administration of IgM-enriched immunoglobulins as an additional therapy did not have a beneficial effect in patients with severe ARDS requiring ECMO support. TRIAL REGISTRATION: Clinical Trials: NCT02961166; retrospectively registered.",2018 Feb 26,"['Prohaska, Stefanie', 'Schirner, Andrea', 'Bashota, Albina', 'Körner, Andreas', 'Blumenstock, Gunnar', 'Haeberle, Helene A.']",J Intensive Care,,,True
c2fb6867057dd0152657070fde0a4ab564d375c2,PMC,Risk factors associated with exposure to bovine respiratory disease pathogens during the peri-weaning period in dairy bull calves,http://dx.doi.org/10.1186/s12917-018-1372-9,PMC5828089,29482563,CC BY,"BACKGROUND: Bovine respiratory disease (BRD) remains among the leading causes of death of cattle internationally. The objective of this study was to identify risk factors associated with exposure to BRD pathogens during the peri-weaning period (day (d)-14 to d 14 relative to weaning at 0) in dairy bull calves using serological responses to these pathogens as surrogate markers of exposure. Clinically normal Holstein-Friesian and Jersey breed bull calves (n = 72) were group housed in 4 pens using a factorial design with calves of different breeds and planes of nutrition in each pen. Intrinsic, management and clinical data were collected during the pre-weaning (d − 56 to d − 14) period. Calves were gradually weaned over 14 days (d − 14 to d 0). Serological analysis for antibodies against key BRD pathogens (BRSV, BPI3V, BHV-1, BHV-4, BCoV, BVDV and H. somni) was undertaken at d − 14 and d 14. Linear regression models (for BVDV, BPI3V, BHV-1, BHV-4, BCoV and H. somni) and a single mixed effect random variable model (for BRSV) were used to identify risk factors for changes in antibody levels to these pathogens. RESULTS: BRSV was the only pathogen which demonstrated clustering by pen. Jersey calves experienced significantly lower changes in BVDV S/P than Holstein-Friesian calves. Animals with a high maximum respiratory score (≥8) recorded significant increases in H. somni S/P during the peri-weaning period when compared to those with respiratory scores of ≤3. Haptoglobin levels of between 1.32 and 1.60 mg/ml at d − 14 were significantly associated with decreases in BHV-1 S/N during the peri-weaning period. Higher BVDV S/P ratios at d − 14 were significantly correlated with increased changes in serological responses to BHV-4 over the peri-weaning period. CONCLUSIONS: Haptoglobin may have potential as a predictor of exposure to BHV-1. BRSV would appear to play a more significant role at the ‘group’ rather than ‘individual animal’ level. The significant associations between the pre-weaning levels of antibodies to certain BRD pathogens and changes in the levels of antibodies to the various pathogens during the peri-weaning period may reflect a cohort of possibly genetically linked ‘better responders’ among the study population.",2018 Feb 27,"['Murray, Gerard M.', 'More, Simon J.', 'Clegg, Tracy A.', 'Earley, Bernadette', 'O’Neill, Rónan G.', 'Johnston, Dayle', 'Gilmore, John', 'Nosov, Mikhail', 'McElroy, Máire C.', 'Inzana, Thomas J.', 'Cassidy, Joseph P.']",BMC Vet Res,,,True
c2dfec16dd4c29856ec78ecbe519d7ba387f01ab,PMC,Binding determinants in the interplay between porcine aminopeptidase N and enterotoxigenic Escherichia coli F4 fimbriae,http://dx.doi.org/10.1186/s13567-018-0519-9,PMC5828407,29482635,CC BY,"The binding of F4(+) enterotoxigenic Escherichia coli (ETEC) and the specific receptor on porcine intestinal epithelial cells is the initial step in F4(+) ETEC infection. Porcine aminopeptidase N (APN) is a newly discovered receptor for F4 fimbriae that binds directly to FaeG adhesin, which is the major subunit of the F4 fimbriae variants F4ab, F4ac, and F4ad. We used overlapping peptide assays to map the APN-FaeG binding sites, which has facilitated in the identifying the APN-binding amino acids that are located in the same region of FaeG variants, thereby limiting the major binding regions of APN to 13 peptides. To determine the core sequence motif, a panel of FaeG peptides with point mutations and FaeG mutants were constructed. Pull-down and binding reactivity assays using piglet intestines determined that the amino acids G159 of F4ab, N209 and L212 of F4ac, and A200 of F4ad were the critical residues for APN binding of FaeG. We further show using ELISA and confocal microscopy assay that amino acids 553–568, and 652–670 of the APN comprise the linear epitope for FaeG binding in all three F4 fimbriae variants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13567-018-0519-9) contains supplementary material, which is available to authorized users.",2018 Feb 26,"['Xia, Pengpeng', 'Quan, Guomei', 'Yang, Yi', 'Zhao, Jing', 'Wang, Yiting', 'Zhou, Mingxu', 'Hardwidge, Philip R.', 'Zhu, Jianzhong', 'Liu, Siguo', 'Zhu, Guoqiang']",Vet Res,,,True
d6a325260dac29bfe718f1e57160583cb23b5908,PMC,The role of renal dipeptidyl peptidase-4 in kidney disease: renal effects of dipeptidyl peptidase-4 inhibitors with a focus on linagliptin,http://dx.doi.org/10.1042/CS20180031,PMC5828949,29491123,CC BY,"Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors used to treat type 2 diabetes may have nephroprotective effects beyond the reduced renal risk conferred by glycemic control. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. The kidneys contain the highest levels of DPP-4, which is increased in diabetic nephropathy. DPP-4 inhibitors are a chemically heterogeneous class of drugs with important pharmacological differences. Of the globally marketed DPP-4 inhibitors, linagliptin is of particular interest for diabetic nephropathy as it is the only compound that is not predominantly excreted in the urine. Linagliptin is also the most potent DPP-4 inhibitor, has the highest affinity for this protein, and has the largest volume of distribution; these properties allow linagliptin to penetrate kidney tissue and tightly bind resident DPP-4. In animal models of kidney disease, linagliptin elicited multiple renoprotective effects, including reducing albuminuria, glomerulosclerosis, and tubulointerstitial fibrosis, independent of changes in glucagon-like peptide-1 (GLP-1) and glucose levels. At the molecular level, linagliptin prevented the pro-fibrotic endothelial-to-mesenchymal transition by disrupting the interaction between membrane-bound DPP-4 and integrin β1 that enhances signaling by transforming growth factor-β1 and vascular endothelial growth factor receptor-1. Linagliptin also increased stromal cell derived factor-1 levels, ameliorated endothelial dysfunction, and displayed unique antioxidant effects. Although the nephroprotective effects of linagliptin are yet to be translated to the clinical setting, the ongoing Cardiovascular and Renal Microvascular Outcome Study with Linagliptin in Patients with Type 2 Diabetes Mellitus (CARMELINA®) study will definitively assess the renal effects of this DPP-4 inhibitor. CARMELINA® is the only clinical trial of a DPP-4 inhibitor powered to evaluate kidney outcomes.",2018 Feb 28,"Kanasaki, Keizo",Clin Sci (Lond),,,True
1aa091c222e1c37ab245b60ed6432ab597480149,PMC,Private collection: high correlation of sample collection and patient admission date in clinical microbiological testing complicates sharing of phylodynamic metadata,http://dx.doi.org/10.1093/ve/vey005,PMC5829646,29511571,CC BY,"Infectious pathogens are known for their rapid evolutionary rates with new mutations arising over days to weeks. The ability to rapidly recover whole genome sequences and analyze the spread and evolution of pathogens using genetic information and pathogen collection dates has lead to interest in real-time tracking of infectious transmission and outbreaks. However, the level of temporal resolution afforded by these analyses may conflict with definitions of what constitutes protected health information (PHI) and privacy requirements for de-identification for publication and public sharing of research data and metadata. In the United States, dates and locations associated with patient care that provide greater resolution than year or the first three digits of the zip code are generally considered patient identifiers. Admission and discharge dates are specifically named as identifiers in Department of Health and Human Services guidance. To understand the degree to which one can impute admission dates from specimen collection dates, we examined sample collection dates and patient admission dates associated with more than 270,000 unique microbiological results from the University of Washington Laboratory Medicine Department between 2010 and 2017. Across all positive microbiological tests, the sample collection date exactly matched the patient admission date in 68.8% of tests. Collection dates and admission dates were identical from emergency department and outpatient testing 86.7% and 96.5% of the time, respectively, with >99% of tests collected within 1 day from the patient admission date. Samples from female patients were significantly more likely to be collected closer to admission date that those from male patients. We show that PHI-associated dates such as admission date can confidently be imputed from deposited collection date. We suggest that publicly depositing microbiological collection dates at greater resolution than the year may not meet routine Safe Harbor-based requirements for patient de-identification. We recommend the use of Expert Determination to determine PHI for a given study and/or direct patient consent if clinical laboratories or phylodynamic practitioners desire to make these data available.",2018 Feb 27,"['Shean, Ryan C', 'Greninger, Alexander L']",Virus Evol,,,True
74c60786e7e6698fa54ae148689fa87501e1cca6,PMC,Implications of asymptomatic carriers for infectious disease transmission and control,http://dx.doi.org/10.1098/rsos.172341,PMC5830799,29515909,CC BY,"For infectious pathogens such as Staphylococcus aureus and Streptococcus pneumoniae, some hosts may carry the pathogen and transmit it to others, yet display no symptoms themselves. These asymptomatic carriers contribute to the spread of disease but go largely undetected and can therefore undermine efforts to control transmission. Understanding the natural history of carriage and its relationship to disease is important for the design of effective interventions to control transmission. Mathematical models of infectious diseases are frequently used to inform decisions about control and should therefore accurately capture the role played by asymptomatic carriers. In practice, incorporating asymptomatic carriers into models is challenging due to the sparsity of direct evidence. This absence of data leads to uncertainty in estimates of model parameters and, more fundamentally, in the selection of an appropriate model structure. To assess the implications of this uncertainty, we systematically reviewed published models of carriage and propose a new model of disease transmission with asymptomatic carriage. Analysis of our model shows how different assumptions about the role of asymptomatic carriers can lead to different conclusions about the transmission and control of disease. Critically, selecting an inappropriate model structure, even when parameters are correctly estimated, may lead to over- or under-estimates of intervention effectiveness. Our results provide a more complete understanding of the role of asymptomatic carriers in transmission and highlight the importance of accurately incorporating carriers into models used to make decisions about disease control.",2018 Feb 14,"['Chisholm, Rebecca H.', 'Campbell, Patricia T.', 'Wu, Yue', 'Tong, Steven Y. C.', 'McVernon, Jodie', 'Geard, Nicholas']",R Soc Open Sci,,,True
91df62f28da6d25c7b5ba9383b75fff8e546f6db,PMC,Implications of asymptomatic carriers for infectious disease transmission and control,http://dx.doi.org/10.1098/rsos.172341,PMC5830799,29515909,CC BY,"For infectious pathogens such as Staphylococcus aureus and Streptococcus pneumoniae, some hosts may carry the pathogen and transmit it to others, yet display no symptoms themselves. These asymptomatic carriers contribute to the spread of disease but go largely undetected and can therefore undermine efforts to control transmission. Understanding the natural history of carriage and its relationship to disease is important for the design of effective interventions to control transmission. Mathematical models of infectious diseases are frequently used to inform decisions about control and should therefore accurately capture the role played by asymptomatic carriers. In practice, incorporating asymptomatic carriers into models is challenging due to the sparsity of direct evidence. This absence of data leads to uncertainty in estimates of model parameters and, more fundamentally, in the selection of an appropriate model structure. To assess the implications of this uncertainty, we systematically reviewed published models of carriage and propose a new model of disease transmission with asymptomatic carriage. Analysis of our model shows how different assumptions about the role of asymptomatic carriers can lead to different conclusions about the transmission and control of disease. Critically, selecting an inappropriate model structure, even when parameters are correctly estimated, may lead to over- or under-estimates of intervention effectiveness. Our results provide a more complete understanding of the role of asymptomatic carriers in transmission and highlight the importance of accurately incorporating carriers into models used to make decisions about disease control.",2018 Feb 14,"['Chisholm, Rebecca H.', 'Campbell, Patricia T.', 'Wu, Yue', 'Tong, Steven Y. C.', 'McVernon, Jodie', 'Geard, Nicholas']",R Soc Open Sci,,,True
11fe16ac2f99335e81c64bb6b83761ed5b700963,PMC,Long Non-Coding RNAs Regulating Immunity in Insects,http://dx.doi.org/10.3390/ncrna3010014,PMC5832008,29657286,CC BY,"Recent advances in modern technology have led to the understanding that not all genetic information is coded into protein and that the genomes of each and every organism including insects produce non-coding RNAs that can control different biological processes. Among RNAs identified in the last decade, long non-coding RNAs (lncRNAs) represent a repertoire of a hidden layer of internal signals that can regulate gene expression in physiological, pathological, and immunological processes. Evidence shows the importance of lncRNAs in the regulation of host–pathogen interactions. In this review, an attempt has been made to view the role of lncRNAs regulating immune responses in insects.",2017 Mar 16,"['Satyavathi, Valluri', 'Ghosh, Rupam', 'Subramanian, Srividya']",Noncoding RNA,,,True
5b34ff95646a7d1127a291315068bf8907e0d301,PMC,Full-length genome sequences of porcine epidemic diarrhoea virus strain CV777; Use of NGS to analyse genomic and sub-genomic RNAs,http://dx.doi.org/10.1371/journal.pone.0193682,PMC5832266,29494671,CC BY,"Porcine epidemic diarrhoea virus, strain CV777, was initially characterized in 1978 as the causative agent of a disease first identified in the UK in 1971. This coronavirus has been widely distributed among laboratories and has been passaged both within pigs and in cell culture. To determine the variability between different stocks of the PEDV strain CV777, sequencing of the full-length genome (ca. 28kb) has been performed in 6 different laboratories, using different protocols. Not surprisingly, each of the different full genome sequences were distinct from each other and from the reference sequence (Accession number AF353511) but they are >99% identical. Unique and shared differences between sequences were identified. The coding region for the surface-exposed spike protein showed the highest proportion of variability including both point mutations and small deletions. The predicted expression of the ORF3 gene product was more dramatically affected in three different variants of this virus through either loss of the initiation codon or gain of a premature termination codon. The genome of one isolate had a substantially rearranged 5´-terminal sequence. This rearrangement was validated through the analysis of sub-genomic mRNAs from infected cells. It is clearly important to know the features of the specific sample of CV777 being used for experimental studies.",2018 Mar 1,"['Rasmussen, Thomas Bruun', 'Boniotti, Maria Beatrice', 'Papetti, Alice', 'Grasland, Béatrice', 'Frossard, Jean-Pierre', 'Dastjerdi, Akbar', 'Hulst, Marcel', 'Hanke, Dennis', 'Pohlmann, Anne', 'Blome, Sandra', 'van der Poel, Wim H. M.', 'Steinbach, Falko', 'Blanchard, Yannick', 'Lavazza, Antonio', 'Bøtner, Anette', 'Belsham, Graham J.']",PLoS One,,,True
61472699f26e3bedce001d84f6e4791ac50652f0,PMC,Hospital Mortality – a neglected but rich source of information supporting the transition to higher quality health systems in low and middle income countries,http://dx.doi.org/10.1186/s12916-018-1024-8,PMC5833062,29495961,CC BY,"BACKGROUND: There is increasing focus on the strength of primary health care systems in low and middle-income countries (LMIC). There are important roles for higher quality district hospital care within these systems. These hospitals are also sources of information of considerable importance to health systems, but this role, as with the wider roles of district hospitals, has been neglected. KEY MESSAGES: As we make efforts to develop higher quality health systems in LMIC we highlight the critical importance of district hospitals focusing here on how data on hospital mortality offers value: i) in understanding disease burden; ii) as part of surveillance and impact monitoring; iii) as an entry point to exploring system failures; and iv) as a lens to examine variability in health system performance and possibly as a measure of health system quality in its own right. However, attention needs paying to improving data quality by addressing reporting gaps and cause of death reporting. Ideally enabling the collection of basic, standardised patient level data might support at least simple case-mix and case-severity adjustment helping us understand variation. Better mortality data could support impact evaluation, benchmarking, exploration of links between health system inputs and outcomes and critical scrutiny of geographic variation in quality and outcomes of care. Improved hospital information is a neglected but broadly valuable public good. CONCLUSION: Accurate, complete and timely hospital mortality reporting is a key attribute of a functioning health system. It can support countries’ efforts to transition to higher quality health systems in LMIC enabling national and local advocacy, accountability and action.",2018 Mar 1,"['English, Mike', 'Mwaniki, Paul', 'Julius, Thomas', 'Chepkirui, Mercy', 'Gathara, David', 'Ouma, Paul O.', 'Cherutich, Peter', 'Okiro, Emelda A.', 'Snow, Robert W.']",BMC Med,,,True
ecf2675fbb7883ca4a8f98c34eadb55c6b857aaa,PMC,Targeting deubiquitinase USP28 for cancer therapy,http://dx.doi.org/10.1038/s41419-017-0208-z,PMC5833459,29415985,CC BY,"As one of the most important post-translational modifications, ubiquitination plays versatile roles in cancer-related pathways, and is involved in protein metabolism, cell-cycle progression, apoptosis, and transcription. Counteracting the activities of the E3 ligases, the deubiquitylating enzymes have been suggested as another important mechanism to modulate the ubiquitination process, and are implicated in cancer as well. In this article, we review the emerging roles of USP28 in cancer pathways as revealed by recent studies. We discuss the major mechanisms by which USP28 is involved in the cancer-related pathways, whereby USP28 regulates physiological homeostasis of ubiquitination process, DNA-damage response, and cell cycle during genotoxic stress. We further review the studies where USP28 was targeted for treating multiples cancers including non-small cell lung cancer, breast cancer, intestinal cancers, gliomas, and bladder cancer. As a result, the clinical significance of targeting USP28 for cancer therapy merits further exploration and demonstration.",2018 Feb 7,"['Wang, Xiaofang', 'Liu, Zhiyi', 'Zhang, Li', 'Yang, Zhaozhi', 'Chen, Xingxing', 'Luo, Jurui', 'Zhou, Zhirui', 'Mei, Xin', 'Yu, Xiaoli', 'Shao, Zhimin', 'Feng, Yan', 'Fu, Shen', 'Zhang, Zhen', 'Wei, Dongping', 'Jia, Lijun', 'Ma, Jinli', 'Guo, Xiaomao']",Cell Death Dis,,,True
19758fc382a2921a000c9d85a33300d3e3b0e2b4,PMC,Multifunctional viral protein γ34.5 manipulates nucleolar protein NOP53 for optimal viral replication of HSV-1,http://dx.doi.org/10.1038/s41419-017-0116-2,PMC5833762,29367603,CC BY,"To ensure efficient virus replication, herpes simplex virus type 1 (HSV-1) encodes several viral proteins to counter host defense response upon infection. Among these proteins, the multifunctional viral protein γ34.5 crucially interferes with or disrupts several antiviral pathways at multiple levels. The current study shows that γ34.5 utilizes nucleolar protein NOP53 to facilitate the dephosphorylation of eukaryotic initiation factor eIF2α for efficient viral translation. Our study shows that: (1) ectopic expression of NOP53 greatly increases the intracellular and extracellular viral yields of HSV-1 (wild strain F) in type I interferon-deficient Vero cells, and more subtly promotes viral replication of γ34.5 deletion mutant virus HSV-1/Δγ34.5. (2) NOP53 is migrated from nuclei in HSV-1/F infected cells, but is redistributed incompletely after infection by either HSV-1/Δγ34.5 or ICP4 deletion mutant virus HSV-1/d120 (replication inadequate). Ectopic expression of γ34.5, consequently, induces cytoplasmic translocation of NOP53 in response to HSV-1/Δγ34.5 infection. (3) Increase of NOP53, in two forms of transient transfection and in vitro expression, attenuates the phosphorylation level of eIF2α in HSV-1/F infected cells, but fails to affect eIF2α phosphorylation induced by HSV-1/Δγ34.5 infection. (4) Knockdown of NOP53, which impairs the specific interaction between γ34.5 and protein phosphatase PP1α, disrupts the ability of γ34.5 to maintain HSV-1 virulence. (5) NOP53 knockdown also significantly reduces tissue damage and decreases viral yield in livers of HSV-1 infected mice. Our findings expand the understanding of the underlying mechanism by which viral protein γ34.5 induces NOP53 redistribution; cytoplasmic NOP53 facilitates γ34.5 recruitment of PP1α to dephosphorylate eIF2α, for optimal viral replication. This paper also demonstrates that blocking the specific interaction between γ34.5 and PP1α would be a useful approach for the development of antiviral agents.",2018 Jan 24,"['Meng, Wen', 'Han, Shi-Chong', 'Li, Cui-Cui', 'Dong, Hui-Jun', 'Wang, Xiao-Jia']",Cell Death Dis,,,True
efbd0dfc426da5dd25ce29411d6fa37571623773,PMC,Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in infected cells reveals ATPase Na(+)/K(+) transporting subunit Alpha 1 and prohibitin as host-cell factors involved in the life cycle of mammarenaviruses,http://dx.doi.org/10.1371/journal.ppat.1006892,PMC5834214,29462184,CC0,"Several mammalian arenaviruses (mammarenaviruses) cause hemorrhagic fevers in humans and pose serious public health concerns in their endemic regions. Additionally, mounting evidence indicates that the worldwide-distributed, prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), is a neglected human pathogen of clinical significance. Concerns about human-pathogenic mammarenaviruses are exacerbated by of the lack of licensed vaccines, and current anti-mammarenavirus therapy is limited to off-label use of ribavirin that is only partially effective. Detailed understanding of virus/host-cell interactions may facilitate the development of novel anti-mammarenavirus strategies by targeting components of the host-cell machinery that are required for efficient virus multiplication. Here we document the generation of a recombinant LCMV encoding a nucleoprotein (NP) containing an affinity tag (rLCMV/Strep-NP) and its use to capture the NP-interactome in infected cells. Our proteomic approach combined with genetics and pharmacological validation assays identified ATPase Na(+)/K(+) transporting subunit alpha 1 (ATP1A1) and prohibitin (PHB) as pro-viral factors. Cell-based assays revealed that ATP1A1 and PHB are involved in different steps of the virus life cycle. Accordingly, we observed a synergistic inhibitory effect on LCMV multiplication with a combination of ATP1A1 and PHB inhibitors. We show that ATP1A1 inhibitors suppress multiplication of Lassa virus and Candid#1, a live-attenuated vaccine strain of Junín virus, suggesting that the requirement of ATP1A1 in virus multiplication is conserved among genetically distantly related mammarenaviruses. Our findings suggest that clinically approved inhibitors of ATP1A1, like digoxin, could be repurposed to treat infections by mammarenaviruses pathogenic for humans.",2018 Feb 20,"['Iwasaki, Masaharu', 'Minder, Petra', 'Caì, Yíngyún', 'Kuhn, Jens H.', 'Yates, John R.', 'Torbett, Bruce E.', 'de la Torre, Juan C.']",PLoS Pathog,,,True
994021cbe306f8833d4124d53771d0038d248860,PMC,Networking of Public Health Microbiology Laboratories Bolsters Europe’s Defenses against Infectious Diseases,http://dx.doi.org/10.3389/fpubh.2018.00046,PMC5834927,29535998,CC BY,"In an era of global health threats caused by epidemics of infectious diseases and rising multidrug resistance, microbiology laboratories provide essential scientific evidence for risk assessment, prevention, and control. Microbiology has been at the core of European infectious disease surveillance networks for decades. Since 2010, these networks have been coordinated by the European Centre for Disease Prevention and Control (ECDC). Activities delivered in these networks include harmonization of laboratory diagnostic, antimicrobial susceptibility and molecular typing methods, multicentre method validation, technical capacity mapping, training of laboratory staff, and continuing quality assessment of laboratory testing. Cooperation among the European laboratory networks in the past 7 years has proved successful in strengthening epidemic preparedness by enabling adaptive capabilities for rapid detection of emerging pathogens across Europe. In partnership with food safety authorities, international public health agencies and learned societies, ECDC-supported laboratory networks have also progressed harmonization of routinely used antimicrobial susceptibility and molecular typing methods, thereby significantly advancing the quality, comparability and precision of microbiological information gathered by ECDC for surveillance for zoonotic diseases and multidrug-resistant pathogens in Europe. ECDC continues to act as a catalyst for sustaining continuous practice improvements and strengthening wider access to laboratory capacity across the European Union. Key priorities include optimization and broader use of rapid diagnostics, further integration of whole-genome sequencing in surveillance and electronic linkage of laboratory and public health systems. This article highlights some of the network contributions to public health in Europe and the role that ECDC plays managing these networks.",2018 Feb 26,"['Albiger, Barbara', 'Revez, Joana', 'Leitmeyer, Katrin Claire', 'Struelens, Marc J.']",Front Public Health,,,True
dd75883b3cd3c5b39b7cc9db85f682047961e1a9,PMC,Transcriptional Innate Immune Response of the Developing Chicken Embryo to Newcastle Disease Virus Infection,http://dx.doi.org/10.3389/fgene.2018.00061,PMC5835104,29535762,CC BY,"Traditional approaches to assess the immune response of chickens to infection are through animal trials, which are expensive, require enhanced biosecurity, compromise welfare, and are frequently influenced by confounding variables. Since the chicken embryo becomes immunocompetent prior to hatch, we here characterized the transcriptional response of selected innate immune genes to Newcastle disease virus (NDV) infection in chicken embryos at days 10, 14, and 18 of embryonic development. The results suggest that the innate immune response 72 h after challenge of 18-day chicken embryo is both consistent and robust. The expression of CCL5, Mx1, and TLR3 in lung tissues of NDV challenged chicken embryos from the outbred Kuroiler and Tanzanian local ecotype lines showed that their expression was several orders of magnitude higher in the Kuroiler than in the local ecotypes. Next, the expression patterns of three additional innate-immunity related genes, IL-8, IRF-1, and STAT1, were examined in the highly congenic Fayoumi (M5.1 and M15.2) and Leghorn (Ghs6 and Ghs13) sublines that differ only at the microchromosome bearing the major histocompatibility locus. The results show that the Ghs13 Leghorn subline had a consistently higher expression of all genes except IL-8 and expression seemed to be subline-dependent rather than breed-dependent, suggesting that the innate immune response of chicken embryos to NDV infection may be genetically controlled by the MHC-locus. Taken together, the results suggest that the chicken embryo may represent a promising model to studying the patterns and sources of variation of the avian innate immune response to infection with NDV and related pathogens.",2018 Feb 27,"['Schilling, Megan A.', 'Katani, Robab', 'Memari, Sahar', 'Cavanaugh, Meredith', 'Buza, Joram', 'Radzio-Basu, Jessica', 'Mpenda, Fulgence N.', 'Deist, Melissa S.', 'Lamont, Susan J.', 'Kapur, Vivek']",Front Genet,,,True
fcd9e38e06549c39625f00187d5b8f4a769b584f,PMC,Critical neutralizing fragment of Zika virus EDIII elicits cross-neutralization and protection against divergent Zika viruses,http://dx.doi.org/10.1038/s41426-017-0007-8,PMC5837162,29362446,CC BY,"Zika virus (ZIKV) infection remains a serious health threat due to its close association with congenital Zika syndrome (CZS), which includes microcephaly and other severe birth defects. As no vaccines are available for human use, continuous effort is needed to develop effective and safe vaccines to prevent ZIKV infection. In this study, we constructed three recombinant proteins comprising, respectively, residues 296–406 (E296-406), 298–409 (E298-409), and 301–404 (E301-404) of ZIKV envelope (E) protein domain III (EDIII) fused with a C-terminal Fc of human IgG. Our results demonstrated that E298-409 induced the highest titer of neutralizing antibodies against infection with nine ZIKV strains isolated from different hosts, countries, and time periods, and it maintained long-term anti-ZIKV immunogenicity to induce neutralizing antibodies. Pups born to mice immunized with E298-409 were fully protected against lethal challenge with two epidemic human ZIKV strains, 2015/Honduras (R103451) and 2015/Colombia (FLR). Passive transfer of anti-E298-409 mouse sera protected pups born to naive mice, as well as type I interferon receptor-deficient adult A129 mice, from lethal challenge with human ZIKV strains R103451 and FLR, and this protection was positively correlated with neutralizing antibodies. These data suggest that the critical neutralizing fragment (i.e., a fragment that can induce highly potent neutralizing antibodies against divergent ZIKV strains) of ZIKV EDIII is a good candidate for development as an effective and safe ZIKV subunit vaccine to protect pregnant mothers and their fetuses against ZIKV infection. The E298-409-specific antibodies can be used for passive immunization to prevent ZIKV infection in newborns or immunocompromised adults.",2018 Jan 24,"['Tai, Wanbo', 'He, Lei', 'Wang, Yufei', 'Sun, Shihun', 'Zhao, Guangyu', 'Luo, Chuming', 'Li, Pei', 'Zhao, Haiyan', 'Fremont, Daved H.', 'Li, Fang', 'Jiang, Shibo', 'Zhou, Yusen', 'Du, Lanying']",Emerg Microbes Infect,,,True
4e70161128a045145f613dfd2029d383e4dde823,PMC,Emerging Concepts of Data Integration in Pathogen Phylodynamics,http://dx.doi.org/10.1093/sysbio/syw054,PMC5837209,28173504,CC BY,"Phylodynamics has become an increasingly popular statistical framework to extract evolutionary and epidemiological information from pathogen genomes. By harnessing such information, epidemiologists aim to shed light on the spatio-temporal patterns of spread and to test hypotheses about the underlying interaction of evolutionary and ecological dynamics in pathogen populations. Although the field has witnessed a rich development of statistical inference tools with increasing levels of sophistication, these tools initially focused on sequences as their sole primary data source. Integrating various sources of information, however, promises to deliver more precise insights in infectious diseases and to increase opportunities for statistical hypothesis testing. Here, we review how the emerging concept of data integration is stimulating new advances in Bayesian evolutionary inference methodology which formalize a marriage of statistical thinking and evolutionary biology. These approaches include connecting sequence to trait evolution, such as for host, phenotypic and geographic sampling information, but also the incorporation of covariates of evolutionary and epidemic processes in the reconstruction procedures. We highlight how a full Bayesian approach to covariate modeling and testing can generate further insights into sequence evolution, trait evolution, and population dynamics in pathogen populations. Specific examples demonstrate how such approaches can be used to test the impact of host on rabies and HIV evolutionary rates, to identify the drivers of influenza dispersal as well as the determinants of rabies cross-species transmissions, and to quantify the evolutionary dynamics of influenza antigenicity. Finally, we briefly discuss how data integration is now also permeating through the inference of transmission dynamics, leading to novel insights into tree-generative processes and detailed reconstructions of transmission trees. [Bayesian inference; birth–death models; coalescent models; continuous trait evolution; covariates; data integration; discrete trait evolution; pathogen phylodynamics.",2017 Jan 6,"['Baele, Guy', 'Suchard, Marc A.', 'Rambaut, Andrew', 'Lemey, Philippe']",Syst Biol,,,True
64ee665b9ca47283ff31e1789655e70838efc849,PMC,Cohort Profile: The Flu Watch Study,http://dx.doi.org/10.1093/ije/dyv370,PMC5837336,26940466,CC BY,,2017 Apr 3,"['Fragaszy, Ellen B', 'Warren-Gash, Charlotte', 'Wang, Lili', 'Copas, Andrew', 'Dukes, Oliver', 'Edmunds, W John', 'Goonetilleke, Nilu', 'Harvey, Gabrielle', 'Johnson, Anne M', 'Kovar, Jana', 'Lim, Megan SC', 'McMichael, Andrew', 'Millett, Elizabeth RC', 'Nazareth, Irwin', 'Nguyen-Van-Tam, Jonathan S', 'Tabassum, Faiza', 'Watson, John M', 'Wurie, Fatima', 'Zambon, Maria', 'Hayward, Andrew C', None]",Int J Epidemiol,,,True
b5535ddf603f7b3b78897553296917cad0c0a789,PMC,Role of Lactobacilli and Lactoferrin in the Mucosal Cervicovaginal Defense,http://dx.doi.org/10.3389/fimmu.2018.00376,PMC5837981,29545798,CC BY,"The innate defense system of the female mucosal genital tract involves a close and complex interaction among the healthy vaginal microbiota, different cells, and various proteins that protect the host from pathogens. Vaginal lactobacilli and lactoferrin represent two essential actors in the vaginal environment. Lactobacilli represent the dominant bacterial species able to prevent facultative and obligate anaerobes outnumber in vaginal microbiota maintaining healthy microbial homeostasis. Several mechanisms underlie the protection exerted by lactobacilli: competition for nutrients and tissue adherence, reduction of the vaginal pH, modulation of immunity, and production of bioactive compounds. Among bioactive factors of cervicovaginal mucosa, lactoferrin, an iron-binding cationic glycoprotein, is a multifunctional glycoprotein with antibacterial, antifungal, antiviral, and antiparasitic activities, recently emerging as an important modulator of inflammation. Lactobacilli and lactoferrin are largely under the influence of female hormones and of paracrine production of various cytokines. Lactoferrin is strongly increased in lower genital tract mucosal fluid of women affected by Neisseria gonorrheae, Chlamydia trachomatis, and Trichomonas vaginalis infections promoting both innate and adaptive immune responses. In vaginal dysbiosis characterized by low amounts of vaginal lactobacilli and increased levels of endogenous anaerobic bacteria, the increase in lactoferrin could act as an immune modulator assuming the role normally played by the healthy microbiota in vaginal mucosa. Then lactoferrin and lactobacilli may be considered as biomarkers of altered microbial homeostasis at vaginal level. Considering the shortage of effective treatments to counteract recurrent and/or antibiotic-resistant bacterial infections, the intravaginal administration of lactobacilli and lactoferrin could be a novel efficient therapeutic strategy and a valuable tool to restore mucosal immune homeostasis.",2018 Mar 1,"['Valenti, Piera', 'Rosa, Luigi', 'Capobianco, Daniela', 'Lepanto, Maria Stefania', 'Schiavi, Elisa', 'Cutone, Antimo', 'Paesano, Rosalba', 'Mastromarino, Paola']",Front Immunol,,,True
512ad31f56a7be38e686f3864431191b0b9f659e,PMC,Punica granatum L. Leaf Extract Attenuates Lung Inflammation in Mice with Acute Lung Injury,http://dx.doi.org/10.1155/2018/6879183,PMC5838491,29675437,CC BY,"The hydroalcoholic extract of Punica granatum (pomegranate) leaves was previously demonstrated to be anti-inflammatory in a rat model of lipopolysaccharide- (LPS-) induced acute peritonitis. Here, we investigated the anti-inflammatory effects of the ethyl acetate fraction obtained from the pomegranate leaf hydroalcoholic extract (EAFPg) on the LPS-induced acute lung injury (ALI) mouse model. Male Swiss mice received either EAFPg at different doses or dexamethasone (per os) prior to LPS intranasal instillation. Vehicle-treated mice were used as controls. Animals were culled at 4 h after LPS challenge, and the bronchoalveolar lavage fluid (BALF) and lung samples were collected for analysis. EAFPg and kaempferol effects on NO and cytokine production by LPS-stimulated RAW 264.7 macrophages were also investigated. Pretreatment with EAFPg (100–300 mg/kg) markedly reduced cell accumulation (specially neutrophils) and collagen deposition in the lungs of ALI mice. The same animals presented with reduced lung and BALF TNF-α and IL-1β expression in comparison with vehicle controls (p < 0.05). Additionally, incubation with either EAFPg or kaempferol (100 μg/ml) reduced NO production and cytokine gene expression in cultured LPS-treated RAW 264.7 macrophages. Overall, these results demonstrate that the prophylactic treatment with EAFPg attenuates acute lung inflammation. We suggest this fraction may be useful in treating ALI.",2018 Feb 20,"['Pinheiro, Aruanã Joaquim Matheus Costa Rodrigues', 'Gonçalves, Jaciara Sá', 'Dourado, Ádylla Wilenna Alves', 'de Sousa, Eduardo Martins', 'Brito, Natilene Mesquita', 'Silva, Lanna Karinny', 'Batista, Marisa Cristina Aranha', 'de Sá, Joicy Cortez', 'Monteiro, Cinara Regina Aragão Vieira', 'Fernandes, Elizabeth Soares', 'Monteiro-Neto, Valério', 'Campbell, Lee Ann', 'Zago, Patrícia Maria Wiziack', 'Lima-Neto, Lidio Gonçalves']",J Immunol Res,,,True
962349fd2566b8fb0ebe7e69aa8998151de7d9ed,PMC,Corrigendum to “A Rare Cause of Childhood Cerebellitis-Influenza Infection: A Case Report and Systematic Review of Literature”,http://dx.doi.org/10.1155/2018/5781843,PMC5838493,29527376,CC BY,,2018 Feb 20,"['Gökçe, Şule', 'Kurugol, Zafer', 'Aslan, Aslı', 'Çiçek, Candan']",Case Rep Pediatr,,,True
96e0e866617d780ddfa44b216491a00a049afd90,PMC,Analysis and Numerical Simulations of a Stochastic SEIQR Epidemic System with Quarantine-Adjusted Incidence and Imperfect Vaccination,http://dx.doi.org/10.1155/2018/7873902,PMC5838506,29675054,CC BY,"This paper considers a high-dimensional stochastic SEIQR (susceptible-exposed-infected-quarantined-recovered) epidemic model with quarantine-adjusted incidence and the imperfect vaccination. The main aim of this study is to investigate stochastic effects on the SEIQR epidemic model and obtain its thresholds. We first obtain the sufficient condition for extinction of the disease of the stochastic system. Then, by using the theory of Hasminskii and the Lyapunov analysis methods, we show there is a unique stationary distribution of the stochastic system and it has an ergodic property, which means the infectious disease is prevalent. This implies that the stochastic disturbance is conducive to epidemic diseases control. At last, computer numerical simulations are carried out to illustrate our theoretical results.",2018 Feb 20,"['Li, Fei', 'Meng, Xinzhu', 'Wang, Xinzeng']",Comput Math Methods Med,,,True
792956320e7955328ce6f1d6cfacff64d1338c5b,PMC,Selection of suitable reference genes for normalization of quantitative RT-PCR (RT-qPCR) expression data across twelve tissues of riverine buffaloes (Bubalus bubalis),http://dx.doi.org/10.1371/journal.pone.0191558,PMC5839537,29509770,CC BY,"Selection of reference genes has become an integral step in any real time quantitative PCR (RT-qPCR) based expression studies. The importance of this study stems from the fact that riverine buffaloes are major dairy species of Indian sub-continent and the information generated here will be of great interest to the investigators engaged in functional genomic studies of this important livestock species. In this study, an effort was made to evaluate a panel of 10 candidate reference genes (glyceraldehyde 3-phosphate dehydrogenase (GAPDH), beta- actin (ACTB), ubiquitously expressed transcript (UXT), ribosomal protein S15 (RPS15), ribosomal protein L-4 (RPL4), ribosomal protein S9 (RPS9), ribosomal protein S23 (RPS23), hydroxymethylbilane synthase (HMBS), β2 Microglobulin (β2M) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) across 12 tissues (mammary gland, kidney, spleen, liver, heart, intestine, ovary, lung, muscle, brain, subcutaneous fat and testis) of riverine buffaloes. In addition to overall analysis, tissue wise evaluation of expression stability of individual RG was also performed. Three different algorithms provided in geNorm, NormFinder and BestKeeper softwares were used to evaluate the stability of 10 potential reference genes from different functional classes. The M-value given by geNorm ranged from 0.9797 (RPS9 and UXT) to 1.7362 (RPS15). From the most stable to the least stable, genes were ranked as: UXT/RPS9> RPL4> RPS23> EEF1A1> ACTB> HMBS> GAPDH> B2M> RPS15. While NormFinder analysis ranked the genes as: UXT> RPS23> RPL4> RPS9> EEF1A1> HMBS> ACTB> β2M> GAPDH> RPS15. Based on the crossing point SD value and range of fold change expression, BestKeeper analysis ranked the genes as: RPS9> RPS23/UXT> RPL4> GAPDH> EEF1A1> ACTB> HMBS> β2M> RPS15. Overall the study has identified RPS23, RPS9, RPL4 and UXT genes to be the most stable and appropriate RGs that could be utilized for normalization of transcriptional data in various tissues of buffaloes. This manuscript thus provide useful information on panel of reference genes that could be helpful for researchers conducting functional genomic studies in riverine buffaloes.",2018 Mar 6,"['Kaur, Ramneek', 'Sodhi, Monika', 'Sharma, Ankita', 'Sharma, Vijay Lakshmi', 'Verma, Preeti', 'Swami, Shelesh Kumar', 'Kumari, Parvesh', 'Mukesh, Manishi']",PLoS One,,,True
704eebd9653b61d2dfbe1483d1a616e6836eeec8,PMC,Comparative Evaluation of Three Preprocessing Methods for Extraction and Detection of Influenza A Virus Nucleic Acids from Sputum,http://dx.doi.org/10.3389/fmed.2018.00056,PMC5840144,29552562,CC BY,"Viscous sputum specimens usually cannot undergo automated extraction, and thus, a pre-homogenization process is desirable before isolating nucleic acids for real-time reverse transcription PCR. In this study, we compared three preprocessing methods [preprocessing with normal saline (NS), dithiothreitol (DTT), and proteinase K (PK)] of sputum specimens on the extraction and detection of influenza A virus (IAV) nucleic acids. Based on the experimental results of 217 specimens, we found that DTT and PK could be used to improve the homogenization effects of sputum and increase the positive rates by 5.53–6.91% higher than that of the NS group. Comparison of 49 positive specimens in all of the three groups demonstrated that the threshold cycle values of the DTT group and PK group were significantly lower and their nucleic acid concentration and A(260)/A(280) ratio within 1.8–2.0 were higher than those of the NS group. Thus, sputum homogenization before nucleic acid extraction is essential for the accurate diagnosis of IAV infection.",2018 Mar 2,"['Yu, Fei', 'Qiu, Ting', 'Zeng, Ying', 'Wang, Yiyin', 'Zheng, Shufa', 'Chen, Xiao', 'Chen, Yu']",Front Med (Lausanne),,,True
adca0aec2cb598e223c27174528cac36c4ae057f,PMC,"Dissecting human antibody responses: useful, basic and surprising findings",http://dx.doi.org/10.15252/emmm.201808879,PMC5840544,29363490,CC BY,"Human memory B cells and plasma cells represent a rich source of antibodies that have been selected in response to human pathogens. In the last decade, different methods have been developed to interrogate the human memory repertoire and isolate monoclonal antibodies. I will discuss how a target‐agnostic approach based on high‐throughput screening of antibodies produced by cultured B cells and plasma cells has not only provided potent and broadly neutralizing antibodies against a range of pathogens, but has also advanced our understanding of basic aspects of the immune response, from host–pathogen interaction to the role of somatic mutations in affinity maturation and in the diversification of the antibody response. Most surprisingly, this approach has also revealed a new mechanism of diversification based on templated insertion of non‐Ig DNA into antibody genes that we discovered in the context of the immune response to malaria infection.",2018 Mar 23,"Lanzavecchia, Antonio",EMBO Mol Med,,,True
d7531ccb3a8417e35a8a34badd9ae40ea731c7fe,PMC,Marmota himalayana in the Qinghai–Tibetan plateau as a special host for bi-segmented and unsegmented picobirnaviruses,http://dx.doi.org/10.1038/s41426-018-0020-6,PMC5841229,29511159,CC BY,"Wildlife has been considered the main source of novel viruses causing emerging infectious diseases. Marmota himalayana is endemic to the Qinghai–Tibetan Plateau, China. Here, based on a high-throughput method using Illumina RNA sequencing, we studied the RNA virome of M. himalayana and discovered multiple novel viruses, especially picobirnaviruses (PBVs), which have a bi-segmented genome and belong to the family Picobirnaviridae. A total of 63% of the viral contigs corresponded to PBVs, comprising 274 segment 1 and 56 segment 2 sequences. Unexpectedly, four unsegmented PBV genomes were also detected and confirmed by PCR and resequencing. According to the phylogenetic analysis, the following nine PBV assortment types are proposed: C1:GI, C2:GIV, C4:GI, C4:GV, C5:GI, C7:GI, C8:GIV, C8:GV and C8:GII. We hypothesize a model of segmentation for the PBV genome, mediated by a 6-bp direct repeat sequence, GAAAGG. The model is supported by detection of the segmentation-associated sequence GAAAGG not only in the 5′ untranslated regions of segment 1 (221 in 289) and segment 2 (57 in 80) of bi-segmented PBVs but also in the 5′ untranslated regions and junction sequences between the capsid and RdRp genes of unsegmented PBVs. Therefore, with RNA sequencing, we found an unexpected biodiversity of PBVs in M. himalayana, indicating that M. himalayana is a special host for PBVs. We also proposed a putative model of how bi-segmented PBVs could be converted into unsegmented PBVs, which sheds new light on the processes of RNA virus genome evolution.",2018 Mar 7,"['Luo, Xue-lian', 'Lu, Shan', 'Jin, Dong', 'Yang, Jing', 'Wu, Shu-sheng', 'Xu, Jianguo']",Emerg Microbes Infect,,,True
08e6a1b558bcb3962378851963c2e67681dabad6,PMC,Rapid detection of MERS coronavirus-like viruses in bats: potential for tracking MERS coronavirus transmission and animal origin,http://dx.doi.org/10.1038/s41426-017-0016-7,PMC5841240,29511173,CC BY,"Recently, we developed a monoclonal antibody-based rapid nucleocapsid protein detection assay for diagnosis of MERS coronavirus (MERS-CoV) in humans and dromedary camels. In this study, we examined the usefulness of this assay to detect other lineage C betacoronaviruses closely related to MERS-CoV in bats. The rapid MERS-CoV nucleocapsid protein detection assay was tested positive in 24 (88.9%) of 27 Tylonycteris bat CoV HKU4 (Ty-BatCoV-HKU4) RNA-positive alimentary samples of Tylonycteris pachypus and 4 (19.0%) of 21 Pipistrellus bat CoV HKU5 (Pi-BatCoV-HKU5) RNA-positive alimentary samples of Pipistrellus abramus. There was significantly more Ty-BatCoV-HKU4 RNA-positive alimentary samples than Pi-BatCoV-HKU5 RNA-positive alimentary samples that were tested positive by the rapid MERS-CoV nucleocapsid protein detection assay (P < 0.001 by Chi-square test). The rapid assay was tested negative in all 51 alimentary samples RNA-positive for alphacoronaviruses (Rhinolophus bat CoV HKU2, Myotis bat CoV HKU6, Miniopterus bat CoV HKU8 and Hipposideros batCoV HKU10) and 32 alimentary samples positive for lineage B (SARS-related Rhinolophus bat CoV HKU3) and lineage D (Rousettus bat CoV HKU9) betacoronaviruses. No significant difference was observed between the viral loads of Ty-BatCoV-HKU4/Pi-BatCoV-HKU5 RNA-positive alimentary samples that were tested positive and negative by the rapid test (Mann-Witney U test). The rapid MERS-CoV nucleocapsid protein detection assay is able to rapidly detect lineage C betacoronaviruses in bats. It detected significantly more Ty-BatCoV-HKU4 than Pi-BatCoV-HKU5 because MERS-CoV is more closely related to Ty-BatCoV-HKU4 than Pi-BatCoV-HKU5. This assay will facilitate rapid on-site mass screening of animal samples for ancestors of MERS-CoV and tracking transmission in the related bat species.",2018 Mar 7,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Chen, Yixin', 'Wong, Emily Y. M.', 'Chan, Kwok-Hung', 'Chen, Honglin', 'Zhang, Libiao', 'Xia, Ningshao', 'Yuen, Kwok-Yung']",Emerg Microbes Infect,,,True
2286b53045dda4309a7f4da297e7d1974b1cb0d4,PMC,Acral melanoma detection using a convolutional neural network for dermoscopy images,http://dx.doi.org/10.1371/journal.pone.0193321,PMC5841780,29513718,CC BY,"BACKGROUND/PURPOSE: Acral melanoma is the most common type of melanoma in Asians, and usually results in a poor prognosis due to late diagnosis. We applied a convolutional neural network to dermoscopy images of acral melanoma and benign nevi on the hands and feet and evaluated its usefulness for the early diagnosis of these conditions. METHODS: A total of 724 dermoscopy images comprising acral melanoma (350 images from 81 patients) and benign nevi (374 images from 194 patients), and confirmed by histopathological examination, were analyzed in this study. To perform the 2-fold cross validation, we split them into two mutually exclusive subsets: half of the total image dataset was selected for training and the rest for testing, and we calculated the accuracy of diagnosis comparing it with the dermatologist’s and non-expert’s evaluation. RESULTS: The accuracy (percentage of true positive and true negative from all images) of the convolutional neural network was 83.51% and 80.23%, which was higher than the non-expert’s evaluation (67.84%, 62.71%) and close to that of the expert (81.08%, 81.64%). Moreover, the convolutional neural network showed area-under-the-curve values like 0.8, 0.84 and Youden’s index like 0.6795, 0.6073, which were similar score with the expert. CONCLUSION: Although further data analysis is necessary to improve their accuracy, convolutional neural networks would be helpful to detect acral melanoma from dermoscopy images of the hands and feet.",2018 Mar 7,"['Yu, Chanki', 'Yang, Sejung', 'Kim, Wonoh', 'Jung, Jinwoong', 'Chung, Kee-Yang', 'Lee, Sang Wook', 'Oh, Byungho']",PLoS One,,,True
c09a602a62f8976f5772470145fd98f2abfa1236,PMC,Planning and preparing for public health threats at airports,http://dx.doi.org/10.1186/s12992-018-0323-3,PMC5842601,29514664,CC BY,"The ever-increasing speed and scope of human mobility by international air travel has led to a global transport network for infectious diseases with the potential to introduce pathogens into non-endemic areas, and to facilitate rapid spread of novel or mutated zoonotic agents. Robust national emergency preparedness is vital to mitigate the transmission of infectious diseases agents domestically and to prevent onward spread to other countries. Given the complex range of stakeholders who respond to an infectious disease threat being transmitted through air travel, it is important that protocols be tested and practised extensively in advance of a real emergency. Simulation exercises include the identification of possible scenarios based on the probability of hazards and the vulnerability of populations as a basis for planning, and provide a useful measure of preparedness efforts and capabilities. In October 2016, a live simulation exercise was conducted at a major airport in Ireland incorporating a public health threat for the first time, with the notification of a possible case of MERS-CoV aboard an aircraft plus an undercarriage fire. Strengths of the response to the communicable disease threat included appropriate public health risk assessment, case management, passenger information gathering, notification to relevant parties, and communication to passengers and multiple agencies. Lessons learned include: o Exercise planning should not be overly ambitious. In testing too many facets of emergency response, the public health response could be deprioritised. o The practical implementation of communication protocols in a real-time exercise of this scope proved challenging. These protocols should continue to be checked and tested by desk-top exercises to ensure that all staff concerned are familiar with them, especially in the context of staff turn-over. o The roles and responsibilities of the various agencies must be clear to avoid role confusion. o Equipment and infrastructure capacities must be considered and in place in advance of an actual incident or test, for example whether or not cell phone signals require boosting during a major event. Importantly, exercises bring together individuals representing organisations with different roles and perspectives allowing identification of capabilities and limitations, and problem solving about how to address the gaps and overlaps in a low-threat collaborative setting.",2018 Mar 7,"['Martin, Greg', 'Boland, Mairin']",Global Health,,,True
fae8f01ff5ef7b1737b60dfba0e183bdf482aaba,PMC,Species-specific vulnerability of RanBP2 shaped the evolution of SIV as it transmitted in African apes,http://dx.doi.org/10.1371/journal.ppat.1006906,PMC5843284,29518153,CC BY,"HIV-1 arose as the result of spillover of simian immunodeficiency viruses (SIVs) from great apes in Africa, namely from chimpanzees and gorillas. Chimpanzees and gorillas were, themselves, infected with SIV after virus spillover from African monkeys. During spillover events, SIV is thought to require adaptation to the new host species. The host barriers that drive viral adaptation have predominantly been attributed to restriction factors, rather than cofactors (host proteins exploited to promote viral replication). Here, we consider the role of one cofactor, RanBP2, in providing a barrier that drove viral genome evolution during SIV spillover events. RanBP2 (also known as Nup358) is a component of the nuclear pore complex known to facilitate nuclear entry of HIV-1. Our data suggest that transmission of SIV from monkeys to chimpanzees, and then from chimpanzees to gorillas, both coincided with changes in the viral capsid that allowed interaction with RanBP2 of the new host species. However, human RanBP2 subsequently provided no barrier to the zoonotic transmission of SIV from chimpanzees or gorillas, indicating that chimpanzee- and gorilla-adapted SIVs are pre-adapted to humans in this regard. Our observations are in agreement with RanBP2 driving virus evolution during cross-species transmissions of SIV, particularly in the transmissions to and between great ape species.",2018 Mar 8,"['Meyerson, Nicholas R.', 'Warren, Cody J.', 'Vieira, Daniel A. S. A.', 'Diaz-Griferro, Felipe', 'Sawyer, Sara L.']",PLoS Pathog,,,True
8c96f0ad3a90f415dc80707a5bda39da0cdce5ec,PMC,Species-specific vulnerability of RanBP2 shaped the evolution of SIV as it transmitted in African apes,http://dx.doi.org/10.1371/journal.ppat.1006906,PMC5843284,29518153,CC BY,"HIV-1 arose as the result of spillover of simian immunodeficiency viruses (SIVs) from great apes in Africa, namely from chimpanzees and gorillas. Chimpanzees and gorillas were, themselves, infected with SIV after virus spillover from African monkeys. During spillover events, SIV is thought to require adaptation to the new host species. The host barriers that drive viral adaptation have predominantly been attributed to restriction factors, rather than cofactors (host proteins exploited to promote viral replication). Here, we consider the role of one cofactor, RanBP2, in providing a barrier that drove viral genome evolution during SIV spillover events. RanBP2 (also known as Nup358) is a component of the nuclear pore complex known to facilitate nuclear entry of HIV-1. Our data suggest that transmission of SIV from monkeys to chimpanzees, and then from chimpanzees to gorillas, both coincided with changes in the viral capsid that allowed interaction with RanBP2 of the new host species. However, human RanBP2 subsequently provided no barrier to the zoonotic transmission of SIV from chimpanzees or gorillas, indicating that chimpanzee- and gorilla-adapted SIVs are pre-adapted to humans in this regard. Our observations are in agreement with RanBP2 driving virus evolution during cross-species transmissions of SIV, particularly in the transmissions to and between great ape species.",2018 Mar 8,"['Meyerson, Nicholas R.', 'Warren, Cody J.', 'Vieira, Daniel A. S. A.', 'Diaz-Griferro, Felipe', 'Sawyer, Sara L.']",PLoS Pathog,,,False
4fbae82e9d1072015a50e2417e1b0f27bd5ae43f,PMC,Species-specific vulnerability of RanBP2 shaped the evolution of SIV as it transmitted in African apes,http://dx.doi.org/10.1371/journal.ppat.1006906,PMC5843284,29518153,CC BY,"HIV-1 arose as the result of spillover of simian immunodeficiency viruses (SIVs) from great apes in Africa, namely from chimpanzees and gorillas. Chimpanzees and gorillas were, themselves, infected with SIV after virus spillover from African monkeys. During spillover events, SIV is thought to require adaptation to the new host species. The host barriers that drive viral adaptation have predominantly been attributed to restriction factors, rather than cofactors (host proteins exploited to promote viral replication). Here, we consider the role of one cofactor, RanBP2, in providing a barrier that drove viral genome evolution during SIV spillover events. RanBP2 (also known as Nup358) is a component of the nuclear pore complex known to facilitate nuclear entry of HIV-1. Our data suggest that transmission of SIV from monkeys to chimpanzees, and then from chimpanzees to gorillas, both coincided with changes in the viral capsid that allowed interaction with RanBP2 of the new host species. However, human RanBP2 subsequently provided no barrier to the zoonotic transmission of SIV from chimpanzees or gorillas, indicating that chimpanzee- and gorilla-adapted SIVs are pre-adapted to humans in this regard. Our observations are in agreement with RanBP2 driving virus evolution during cross-species transmissions of SIV, particularly in the transmissions to and between great ape species.",2018 Mar 8,"['Meyerson, Nicholas R.', 'Warren, Cody J.', 'Vieira, Daniel A. S. A.', 'Diaz-Griferro, Felipe', 'Sawyer, Sara L.']",PLoS Pathog,,,False
95984e509080ef051aaa3ceac262d3fb0f421bfd,PMC,Species-specific vulnerability of RanBP2 shaped the evolution of SIV as it transmitted in African apes,http://dx.doi.org/10.1371/journal.ppat.1006906,PMC5843284,29518153,CC BY,"HIV-1 arose as the result of spillover of simian immunodeficiency viruses (SIVs) from great apes in Africa, namely from chimpanzees and gorillas. Chimpanzees and gorillas were, themselves, infected with SIV after virus spillover from African monkeys. During spillover events, SIV is thought to require adaptation to the new host species. The host barriers that drive viral adaptation have predominantly been attributed to restriction factors, rather than cofactors (host proteins exploited to promote viral replication). Here, we consider the role of one cofactor, RanBP2, in providing a barrier that drove viral genome evolution during SIV spillover events. RanBP2 (also known as Nup358) is a component of the nuclear pore complex known to facilitate nuclear entry of HIV-1. Our data suggest that transmission of SIV from monkeys to chimpanzees, and then from chimpanzees to gorillas, both coincided with changes in the viral capsid that allowed interaction with RanBP2 of the new host species. However, human RanBP2 subsequently provided no barrier to the zoonotic transmission of SIV from chimpanzees or gorillas, indicating that chimpanzee- and gorilla-adapted SIVs are pre-adapted to humans in this regard. Our observations are in agreement with RanBP2 driving virus evolution during cross-species transmissions of SIV, particularly in the transmissions to and between great ape species.",2018 Mar 8,"['Meyerson, Nicholas R.', 'Warren, Cody J.', 'Vieira, Daniel A. S. A.', 'Diaz-Griferro, Felipe', 'Sawyer, Sara L.']",PLoS Pathog,,,False
fe89f097d4410854ec82211481a60b10138737aa,PMC,Species-specific vulnerability of RanBP2 shaped the evolution of SIV as it transmitted in African apes,http://dx.doi.org/10.1371/journal.ppat.1006906,PMC5843284,29518153,CC BY,"HIV-1 arose as the result of spillover of simian immunodeficiency viruses (SIVs) from great apes in Africa, namely from chimpanzees and gorillas. Chimpanzees and gorillas were, themselves, infected with SIV after virus spillover from African monkeys. During spillover events, SIV is thought to require adaptation to the new host species. The host barriers that drive viral adaptation have predominantly been attributed to restriction factors, rather than cofactors (host proteins exploited to promote viral replication). Here, we consider the role of one cofactor, RanBP2, in providing a barrier that drove viral genome evolution during SIV spillover events. RanBP2 (also known as Nup358) is a component of the nuclear pore complex known to facilitate nuclear entry of HIV-1. Our data suggest that transmission of SIV from monkeys to chimpanzees, and then from chimpanzees to gorillas, both coincided with changes in the viral capsid that allowed interaction with RanBP2 of the new host species. However, human RanBP2 subsequently provided no barrier to the zoonotic transmission of SIV from chimpanzees or gorillas, indicating that chimpanzee- and gorilla-adapted SIVs are pre-adapted to humans in this regard. Our observations are in agreement with RanBP2 driving virus evolution during cross-species transmissions of SIV, particularly in the transmissions to and between great ape species.",2018 Mar 8,"['Meyerson, Nicholas R.', 'Warren, Cody J.', 'Vieira, Daniel A. S. A.', 'Diaz-Griferro, Felipe', 'Sawyer, Sara L.']",PLoS Pathog,,,False
62775e390d2efb1a5310ba5f0fc1322bee11b601,PMC,Species-specific vulnerability of RanBP2 shaped the evolution of SIV as it transmitted in African apes,http://dx.doi.org/10.1371/journal.ppat.1006906,PMC5843284,29518153,CC BY,"HIV-1 arose as the result of spillover of simian immunodeficiency viruses (SIVs) from great apes in Africa, namely from chimpanzees and gorillas. Chimpanzees and gorillas were, themselves, infected with SIV after virus spillover from African monkeys. During spillover events, SIV is thought to require adaptation to the new host species. The host barriers that drive viral adaptation have predominantly been attributed to restriction factors, rather than cofactors (host proteins exploited to promote viral replication). Here, we consider the role of one cofactor, RanBP2, in providing a barrier that drove viral genome evolution during SIV spillover events. RanBP2 (also known as Nup358) is a component of the nuclear pore complex known to facilitate nuclear entry of HIV-1. Our data suggest that transmission of SIV from monkeys to chimpanzees, and then from chimpanzees to gorillas, both coincided with changes in the viral capsid that allowed interaction with RanBP2 of the new host species. However, human RanBP2 subsequently provided no barrier to the zoonotic transmission of SIV from chimpanzees or gorillas, indicating that chimpanzee- and gorilla-adapted SIVs are pre-adapted to humans in this regard. Our observations are in agreement with RanBP2 driving virus evolution during cross-species transmissions of SIV, particularly in the transmissions to and between great ape species.",2018 Mar 8,"['Meyerson, Nicholas R.', 'Warren, Cody J.', 'Vieira, Daniel A. S. A.', 'Diaz-Griferro, Felipe', 'Sawyer, Sara L.']",PLoS Pathog,,,False
1cbc073d7288259db8f24cd19ee27052c1eece02,PMC,Regulation of Cytokine Production by the Unfolded Protein Response; Implications for Infection and Autoimmunity,http://dx.doi.org/10.3389/fimmu.2018.00422,PMC5844972,29556237,CC BY,"Protein folding in the endoplasmic reticulum (ER) is an essential cell function. To safeguard this process in the face of environmental threats and internal stressors, cells mount an evolutionarily conserved response known as the unfolded protein response (UPR). Invading pathogens induce cellular stress that impacts protein folding, thus the UPR is well situated to sense danger and contribute to immune responses. Cytokines (inflammatory cytokines and interferons) critically mediate host defense against pathogens, but when aberrantly produced, may also drive pathologic inflammation. The UPR influences cytokine production on multiple levels, from stimulation of pattern recognition receptors, to modulation of inflammatory signaling pathways, and the regulation of cytokine transcription factors. This review will focus on the mechanisms underlying cytokine regulation by the UPR, and the repercussions of this relationship for infection and autoimmune/autoinflammatory diseases. Interrogation of viral and bacterial infections has revealed increasing numbers of examples where pathogens induce or modulate the UPR and implicated UPR-modulated cytokines in host response. The flip side of this coin, the UPR/ER stress responses have been increasingly recognized in a variety of autoimmune and inflammatory diseases. Examples include monogenic disorders of ER function, diseases linked to misfolding protein (HLA-B27 and spondyloarthritis), diseases directly implicating UPR and autophagy genes (inflammatory bowel disease), and autoimmune diseases targeting highly secretory cells (e.g., diabetes). Given the burgeoning interest in pharmacologically targeting the UPR, greater discernment is needed regarding how the UPR regulates cytokine production during specific infections and autoimmune processes, and the relative place of this interaction in pathogenesis.",2018 Mar 5,"Smith, Judith A.",Front Immunol,,,True
39f33cf580fe6ce842e2c9005570d08115c3ed4b,PMC,Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease,http://dx.doi.org/10.1128/mBio.00221-18,PMC5844999,29511076,CC BY,"Emerging coronaviruses (CoVs) cause severe disease in humans, but no approved therapeutics are available. The CoV nsp14 exoribonuclease (ExoN) has complicated development of antiviral nucleosides due to its proofreading activity. We recently reported that the nucleoside analogue GS-5734 (remdesivir) potently inhibits human and zoonotic CoVs in vitro and in a severe acute respiratory syndrome coronavirus (SARS-CoV) mouse model. However, studies with GS-5734 have not reported resistance associated with GS-5734, nor do we understand the action of GS-5734 in wild-type (WT) proofreading CoVs. Here, we show that GS-5734 inhibits murine hepatitis virus (MHV) with similar 50% effective concentration values (EC(50)) as SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Passage of WT MHV in the presence of the GS-5734 parent nucleoside selected two mutations in the nsp12 polymerase at residues conserved across all CoVs that conferred up to 5.6-fold resistance to GS-5734, as determined by EC(50). The resistant viruses were unable to compete with WT in direct coinfection passage in the absence of GS-5734. Introduction of the MHV resistance mutations into SARS-CoV resulted in the same in vitro resistance phenotype and attenuated SARS-CoV pathogenesis in a mouse model. Finally, we demonstrate that an MHV mutant lacking ExoN proofreading was significantly more sensitive to GS-5734. Combined, the results indicate that GS-5734 interferes with the nsp12 polymerase even in the setting of intact ExoN proofreading activity and that resistance can be overcome with increased, nontoxic concentrations of GS-5734, further supporting the development of GS-5734 as a broad-spectrum therapeutic to protect against contemporary and emerging CoVs.",2018 Mar 6,"['Agostini, Maria L.', 'Andres, Erica L.', 'Sims, Amy C.', 'Graham, Rachel L.', 'Sheahan, Timothy P.', 'Lu, Xiaotao', 'Smith, Everett Clinton', 'Case, James Brett', 'Feng, Joy Y.', 'Jordan, Robert', 'Ray, Adrian S.', 'Cihlar, Tomas', 'Siegel, Dustin', 'Mackman, Richard L.', 'Clarke, Michael O.', 'Baric, Ralph S.', 'Denison, Mark R.']",mBio,,,True
e990cc7120ae9e3ef809a225842f9d110f38b042,PMC,Preliminary studies on isolates of Clostridium difficile from dogs and exotic pets,http://dx.doi.org/10.1186/s12917-018-1402-7,PMC5845233,29523201,CC BY,"BACKGROUND: Clostridium difficile infection (CDI) is recognised as an emerging disease in both humans and some animal species. During the past few years, insights into human CDI epidemiology changed and C. difficile is also considered as an emerging community-acquired pathogen. Certain ribotypes (RT) are possibly associated with zoonotic transmission. The objective of this study was to assess the presence of C. difficile in a population of pets and to characterise the isolates. RESULTS: Faecal samples from a total of 90 diarrhoeic dogs and 24 from exotic animal species (both diarrhoeic and non-diarrhoeic) were analysed. Clostridium difficile was isolated from 6 (6.7%) dogs and one reptile sample (4.2%). Four (66.7%) of the six dog strains were capable of producing toxins. Four known different RTs were detected in dogs (010, 014, 123 and 358) and a new one was found in a faecal sample of an exotic animal. This new RT isolate was negative for all toxin genes tested and belonged to sequence type 347 which has been proposed as a Clade-III member. Importantly, two dog strains showed a stable resistance to metronidazole (initial MIC values: 128 and 48 μg/ml). CONCLUSIONS: The results obtained in this study suggest the implementation of antimicrobial susceptibility surveillance programs to assess the prevalence of metronidazole resistance in dogs; molecular studies to elucidate C. difficile metronidazole resistance mechanisms are warranted. Based on the similarity between the ribotypes observed in dogs and those described in humans, the zoonotic transmission should be further explored. Furthermore, exotic animals have shown to harbor uncommon C. difficile strains which require further genomic studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1402-7) contains supplementary material, which is available to authorized users.",2018 Mar 9,"['Andrés-Lasheras, Sara', 'Martín-Burriel, Inma', 'Mainar-Jaime, Raúl Carlos', 'Morales, Mariano', 'Kuijper, Ed', 'Blanco, José L.', 'Chirino-Trejo, Manuel', 'Bolea, Rosa']",BMC Vet Res,,,True
61be2db10d752ec61e879d76e6328b6d676a0f55,PMC,TANK-Binding Kinase 1-Dependent Responses in Health and Autoimmunity,http://dx.doi.org/10.3389/fimmu.2018.00434,PMC5845716,29559975,CC BY,"The pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is driven by genetic predisposition and environmental triggers that lead to dysregulated immune responses. These include the generation of pathogenic autoantibodies and aberrant production of inflammatory cytokines. Current therapies for RA and other autoimmune diseases reduce inflammation by targeting inflammatory mediators, most of which are innate response cytokines, resulting in generalized immunosuppression. Overall, this strategy has been very successful, but not all patients respond, responses can diminish over time and numerous side effects can occur. Therapies that target the germinal center (GC) reaction and/or antibody-secreting plasma cells (PC) potentially provide a novel approach. TANK-binding kinase 1 (TBK1) is an IKK-related serine/threonine kinase best characterized for its involvement in innate antiviral responses through the induction of type I interferons. TBK1 is also gaining attention for its roles in humoral immune responses. In this review, we discuss the role of TBK1 in immunological pathways involved in the development and maintenance of antibody responses, with particular emphasis on its potential relevance in the pathogenesis of humoral autoimmunity. First, we review the role of TBK1 in the induction of type I IFNs. Second, we highlight how TBK1 mediates inducible T cell co-stimulator signaling to the GC T follicular B helper population. Third, we discuss emerging evidence on the contribution of TBK1 to autophagic pathways and the potential implications for immune cell function. Finally, we discuss the therapeutic potential of TBK1 inhibition in autoimmunity.",2018 Mar 6,"['Louis, Cynthia', 'Burns, Chris', 'Wicks, Ian']",Front Immunol,,,True
64b4ec9158c8f378000f3d15492f317f19baeafb,PMC,Lipid-Based Particles: Versatile Delivery Systems for Mucosal Vaccination against Infection,http://dx.doi.org/10.3389/fimmu.2018.00431,PMC5845866,29563912,CC BY,"Vaccination is the process of administering immunogenic formulations in order to induce or harness antigen (Ag)-specific antibody and T cell responses in order to protect against infections. Important successes have been obtained in protecting individuals against many deleterious pathological situations after parenteral vaccination. However, one of the major limitations of the current vaccination strategies is the administration route that may not be optimal for the induction of immunity at the site of pathogen entry, i.e., mucosal surfaces. It is now well documented that immune responses along the genital, respiratory, or gastrointestinal tracts have to be elicited locally to ensure efficient trafficking of effector and memory B and T cells to mucosal tissues. Moreover, needle-free mucosal delivery of vaccines is advantageous in terms of safety, compliance, and ease of administration. However, the quest for mucosal vaccines is challenging due to (1) the fact that Ag sampling has to be performed across the epithelium through a relatively limited number of portals of entry; (2) the deleterious acidic and proteolytic environment of the mucosae that affect the stability, integrity, and retention time of the applied Ags; and (3) the tolerogenic environment of mucosae, which requires the addition of adjuvants to elicit efficient effector immune responses. Until now, only few mucosally applicable vaccine formulations have been developed and successfully tested. In animal models and clinical trials, the use of lipidic structures such as liposomes, virosomes, immune stimulating complexes, gas-filled microbubbles and emulsions has proven efficient for the mucosal delivery of associated Ags and the induction of local and systemic immune reponses. Such particles are suitable for mucosal delivery because they protect the associated payload from degradation and deliver concentrated amounts of Ags via specialized sampling cells (microfold cells) within the mucosal epithelium to underlying antigen-presenting cells. The review aims at summarizing recent development in the field of mucosal vaccination using lipid-based particles. The modularity ensured by tailoring the lipidic design and content of particles, and their known safety as already established in humans, make the continuing appraisal of these vaccine candidates a promising development in the field of targeted mucosal vaccination.",2018 Mar 7,"['Corthésy, Blaise', 'Bioley, Gilles']",Front Immunol,,,True
c27741de244a87a624f556884b3d2ffffdf9b4ec,PMC,Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy,http://dx.doi.org/10.1371/journal.pone.0194225,PMC5846794,29529088,CC BY,"Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways. In addition to muscle-related functions, we identified other biological processes such as apoptosis, signaling in the immune system and neurotrophin signaling as significantly modulated in patients compared with controls. Moreover, our network-based analysis identified the involvement of FoxO transcription factors as putative regulators of different pathways. On the whole, this study provided a global view of the molecular processes involved in Duchenne muscular dystrophy that are decipherable from serum proteome.",2018 Mar 12,"['Parolo, Silvia', 'Marchetti, Luca', 'Lauria, Mario', 'Misselbeck, Karla', 'Scott-Boyer, Marie-Pier', 'Caberlotto, Laura', 'Priami, Corrado']",PLoS One,,,True
0ea910c4b966ee169f4cc80cfca5a451425e351f,PMC,Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy,http://dx.doi.org/10.1371/journal.pone.0194225,PMC5846794,29529088,CC BY,"Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways. In addition to muscle-related functions, we identified other biological processes such as apoptosis, signaling in the immune system and neurotrophin signaling as significantly modulated in patients compared with controls. Moreover, our network-based analysis identified the involvement of FoxO transcription factors as putative regulators of different pathways. On the whole, this study provided a global view of the molecular processes involved in Duchenne muscular dystrophy that are decipherable from serum proteome.",2018 Mar 12,"['Parolo, Silvia', 'Marchetti, Luca', 'Lauria, Mario', 'Misselbeck, Karla', 'Scott-Boyer, Marie-Pier', 'Caberlotto, Laura', 'Priami, Corrado']",PLoS One,,,False
8ce9667769c5170088143a572ee8b7fff299b978,PMC,Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy,http://dx.doi.org/10.1371/journal.pone.0194225,PMC5846794,29529088,CC BY,"Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways. In addition to muscle-related functions, we identified other biological processes such as apoptosis, signaling in the immune system and neurotrophin signaling as significantly modulated in patients compared with controls. Moreover, our network-based analysis identified the involvement of FoxO transcription factors as putative regulators of different pathways. On the whole, this study provided a global view of the molecular processes involved in Duchenne muscular dystrophy that are decipherable from serum proteome.",2018 Mar 12,"['Parolo, Silvia', 'Marchetti, Luca', 'Lauria, Mario', 'Misselbeck, Karla', 'Scott-Boyer, Marie-Pier', 'Caberlotto, Laura', 'Priami, Corrado']",PLoS One,,,False
84665831feb210bed4a59cae7b046cfc08aa37c5,PMC,Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy,http://dx.doi.org/10.1371/journal.pone.0194225,PMC5846794,29529088,CC BY,"Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways. In addition to muscle-related functions, we identified other biological processes such as apoptosis, signaling in the immune system and neurotrophin signaling as significantly modulated in patients compared with controls. Moreover, our network-based analysis identified the involvement of FoxO transcription factors as putative regulators of different pathways. On the whole, this study provided a global view of the molecular processes involved in Duchenne muscular dystrophy that are decipherable from serum proteome.",2018 Mar 12,"['Parolo, Silvia', 'Marchetti, Luca', 'Lauria, Mario', 'Misselbeck, Karla', 'Scott-Boyer, Marie-Pier', 'Caberlotto, Laura', 'Priami, Corrado']",PLoS One,,,False
2c2d480372952088e001aea8ccffb9d5ee1757a7,PMC,Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy,http://dx.doi.org/10.1371/journal.pone.0194225,PMC5846794,29529088,CC BY,"Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways. In addition to muscle-related functions, we identified other biological processes such as apoptosis, signaling in the immune system and neurotrophin signaling as significantly modulated in patients compared with controls. Moreover, our network-based analysis identified the involvement of FoxO transcription factors as putative regulators of different pathways. On the whole, this study provided a global view of the molecular processes involved in Duchenne muscular dystrophy that are decipherable from serum proteome.",2018 Mar 12,"['Parolo, Silvia', 'Marchetti, Luca', 'Lauria, Mario', 'Misselbeck, Karla', 'Scott-Boyer, Marie-Pier', 'Caberlotto, Laura', 'Priami, Corrado']",PLoS One,,,False
113a5f669f3b4dcd38b3761a7594be9c67113acd,PMC,Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy,http://dx.doi.org/10.1371/journal.pone.0194225,PMC5846794,29529088,CC BY,"Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways. In addition to muscle-related functions, we identified other biological processes such as apoptosis, signaling in the immune system and neurotrophin signaling as significantly modulated in patients compared with controls. Moreover, our network-based analysis identified the involvement of FoxO transcription factors as putative regulators of different pathways. On the whole, this study provided a global view of the molecular processes involved in Duchenne muscular dystrophy that are decipherable from serum proteome.",2018 Mar 12,"['Parolo, Silvia', 'Marchetti, Luca', 'Lauria, Mario', 'Misselbeck, Karla', 'Scott-Boyer, Marie-Pier', 'Caberlotto, Laura', 'Priami, Corrado']",PLoS One,,,False
7a8d37b060b1c22e1dde19c72e702707f78e5e5b,PMC,Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy,http://dx.doi.org/10.1371/journal.pone.0194225,PMC5846794,29529088,CC BY,"Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways. In addition to muscle-related functions, we identified other biological processes such as apoptosis, signaling in the immune system and neurotrophin signaling as significantly modulated in patients compared with controls. Moreover, our network-based analysis identified the involvement of FoxO transcription factors as putative regulators of different pathways. On the whole, this study provided a global view of the molecular processes involved in Duchenne muscular dystrophy that are decipherable from serum proteome.",2018 Mar 12,"['Parolo, Silvia', 'Marchetti, Luca', 'Lauria, Mario', 'Misselbeck, Karla', 'Scott-Boyer, Marie-Pier', 'Caberlotto, Laura', 'Priami, Corrado']",PLoS One,,,False
e51b1b1f217d2a534169ec3fd8b1fb16e8d9a3da,PMC,Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy,http://dx.doi.org/10.1371/journal.pone.0194225,PMC5846794,29529088,CC BY,"Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways. In addition to muscle-related functions, we identified other biological processes such as apoptosis, signaling in the immune system and neurotrophin signaling as significantly modulated in patients compared with controls. Moreover, our network-based analysis identified the involvement of FoxO transcription factors as putative regulators of different pathways. On the whole, this study provided a global view of the molecular processes involved in Duchenne muscular dystrophy that are decipherable from serum proteome.",2018 Mar 12,"['Parolo, Silvia', 'Marchetti, Luca', 'Lauria, Mario', 'Misselbeck, Karla', 'Scott-Boyer, Marie-Pier', 'Caberlotto, Laura', 'Priami, Corrado']",PLoS One,,,False
e7550f29f58fbad80ffeb364d7c9f25accf3578d,PMC,Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy,http://dx.doi.org/10.1371/journal.pone.0194225,PMC5846794,29529088,CC BY,"Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways. In addition to muscle-related functions, we identified other biological processes such as apoptosis, signaling in the immune system and neurotrophin signaling as significantly modulated in patients compared with controls. Moreover, our network-based analysis identified the involvement of FoxO transcription factors as putative regulators of different pathways. On the whole, this study provided a global view of the molecular processes involved in Duchenne muscular dystrophy that are decipherable from serum proteome.",2018 Mar 12,"['Parolo, Silvia', 'Marchetti, Luca', 'Lauria, Mario', 'Misselbeck, Karla', 'Scott-Boyer, Marie-Pier', 'Caberlotto, Laura', 'Priami, Corrado']",PLoS One,,,False
e027e6cb7160c850d05d5d51afd59b5a25b9a2a4,PMC,Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy,http://dx.doi.org/10.1371/journal.pone.0194225,PMC5846794,29529088,CC BY,"Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways. In addition to muscle-related functions, we identified other biological processes such as apoptosis, signaling in the immune system and neurotrophin signaling as significantly modulated in patients compared with controls. Moreover, our network-based analysis identified the involvement of FoxO transcription factors as putative regulators of different pathways. On the whole, this study provided a global view of the molecular processes involved in Duchenne muscular dystrophy that are decipherable from serum proteome.",2018 Mar 12,"['Parolo, Silvia', 'Marchetti, Luca', 'Lauria, Mario', 'Misselbeck, Karla', 'Scott-Boyer, Marie-Pier', 'Caberlotto, Laura', 'Priami, Corrado']",PLoS One,,,False
7d104a81649ca80d3e6d0444fa069c60d36d5e84,PMC,Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy,http://dx.doi.org/10.1371/journal.pone.0194225,PMC5846794,29529088,CC BY,"Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways. In addition to muscle-related functions, we identified other biological processes such as apoptosis, signaling in the immune system and neurotrophin signaling as significantly modulated in patients compared with controls. Moreover, our network-based analysis identified the involvement of FoxO transcription factors as putative regulators of different pathways. On the whole, this study provided a global view of the molecular processes involved in Duchenne muscular dystrophy that are decipherable from serum proteome.",2018 Mar 12,"['Parolo, Silvia', 'Marchetti, Luca', 'Lauria, Mario', 'Misselbeck, Karla', 'Scott-Boyer, Marie-Pier', 'Caberlotto, Laura', 'Priami, Corrado']",PLoS One,,,False
8c02fccc9fb52bd1be9498cdf8dda1f4a39962a4,PMC,Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy,http://dx.doi.org/10.1371/journal.pone.0194225,PMC5846794,29529088,CC BY,"Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways. In addition to muscle-related functions, we identified other biological processes such as apoptosis, signaling in the immune system and neurotrophin signaling as significantly modulated in patients compared with controls. Moreover, our network-based analysis identified the involvement of FoxO transcription factors as putative regulators of different pathways. On the whole, this study provided a global view of the molecular processes involved in Duchenne muscular dystrophy that are decipherable from serum proteome.",2018 Mar 12,"['Parolo, Silvia', 'Marchetti, Luca', 'Lauria, Mario', 'Misselbeck, Karla', 'Scott-Boyer, Marie-Pier', 'Caberlotto, Laura', 'Priami, Corrado']",PLoS One,,,True
d708f87604883a93725ea75e83cd0abf907928fd,PMC,Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy,http://dx.doi.org/10.1371/journal.pone.0194225,PMC5846794,29529088,CC BY,"Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways. In addition to muscle-related functions, we identified other biological processes such as apoptosis, signaling in the immune system and neurotrophin signaling as significantly modulated in patients compared with controls. Moreover, our network-based analysis identified the involvement of FoxO transcription factors as putative regulators of different pathways. On the whole, this study provided a global view of the molecular processes involved in Duchenne muscular dystrophy that are decipherable from serum proteome.",2018 Mar 12,"['Parolo, Silvia', 'Marchetti, Luca', 'Lauria, Mario', 'Misselbeck, Karla', 'Scott-Boyer, Marie-Pier', 'Caberlotto, Laura', 'Priami, Corrado']",PLoS One,,,False
552ee0cc0a8266b6c22dbc287bd080513a3374fb,PMC,Prolonging herd immunity to cholera via vaccination: Accounting for human mobility and waning vaccine effects,http://dx.doi.org/10.1371/journal.pntd.0006257,PMC5847240,29489815,CC BY,"BACKGROUND: Oral cholera vaccination is an approach to preventing outbreaks in at-risk settings and controlling cholera in endemic settings. However, vaccine-derived herd immunity may be short-lived due to interactions between human mobility and imperfect or waning vaccine efficacy. As the supply and utilization of oral cholera vaccines grows, critical questions related to herd immunity are emerging, including: who should be targeted; when should revaccination be performed; and why have cholera outbreaks occurred in recently vaccinated populations? METHODS AND FINDINGS: We use mathematical models to simulate routine and mass oral cholera vaccination in populations with varying degrees of migration, transmission intensity, and vaccine coverage. We show that migration and waning vaccine efficacy strongly influence the duration of herd immunity while birth and death rates have relatively minimal impacts. As compared to either periodic mass vaccination or routine vaccination alone, a community could be protected longer by a blended “Mass and Maintain” strategy. We show that vaccination may be best targeted at populations with intermediate degrees of mobility as compared to communities with very high or very low population turnover. Using a case study of an internally displaced person camp in South Sudan which underwent high-coverage mass vaccination in 2014 and 2015, we show that waning vaccine direct effects and high population turnover rendered the camp over 80% susceptible at the time of the cholera outbreak beginning in October 2016. CONCLUSIONS: Oral cholera vaccines can be powerful tools for quickly protecting a population for a period of time that depends critically on vaccine coverage, vaccine efficacy over time, and the rate of population turnover through human mobility. Due to waning herd immunity, epidemics in vaccinated communities are possible but become less likely through complementary interventions or data-driven revaccination strategies.",2018 Feb 28,"['Peak, Corey M.', 'Reilly, Amanda L.', 'Azman, Andrew S.', 'Buckee, Caroline O.']",PLoS Negl Trop Dis,,,True
285bd58ff58e0259f2d4b2b8b886067be1dea021,PMC,General Prediction of Peptide-MHC Binding Modes Using Incremental Docking: A Proof of Concept,http://dx.doi.org/10.1038/s41598-018-22173-4,PMC5847594,29531253,CC BY,"The class I major histocompatibility complex (MHC) is capable of binding peptides derived from intracellular proteins and displaying them at the cell surface. The recognition of these peptide-MHC (pMHC) complexes by T-cells is the cornerstone of cellular immunity, enabling the elimination of infected or tumoral cells. T-cell-based immunotherapies against cancer, which leverage this mechanism, can greatly benefit from structural analyses of pMHC complexes. Several attempts have been made to use molecular docking for such analyses, but pMHC structure remains too challenging for even state-of-the-art docking tools. To overcome these limitations, we describe the use of an incremental meta-docking approach for structural prediction of pMHC complexes. Previous methods applied in this context used specific constraints to reduce the complexity of this prediction problem, at the expense of generality. Our strategy makes no assumption and can potentially be used to predict binding modes for any pMHC complex. Our method has been tested in a re-docking experiment, reproducing the binding modes of 25 pMHC complexes whose crystal structures are available. This study is a proof of concept that incremental docking strategies can lead to general geometry prediction of pMHC complexes, with potential applications for immunotherapy against cancer or infectious diseases.",2018 Mar 12,"['Antunes, Dinler A.', 'Devaurs, Didier', 'Moll, Mark', 'Lizée, Gregory', 'Kavraki, Lydia E.']",Sci Rep,,,False
ec7d9f4fbe48d9c257de95f8a18cc111de8c613c,PMC,General Prediction of Peptide-MHC Binding Modes Using Incremental Docking: A Proof of Concept,http://dx.doi.org/10.1038/s41598-018-22173-4,PMC5847594,29531253,CC BY,"The class I major histocompatibility complex (MHC) is capable of binding peptides derived from intracellular proteins and displaying them at the cell surface. The recognition of these peptide-MHC (pMHC) complexes by T-cells is the cornerstone of cellular immunity, enabling the elimination of infected or tumoral cells. T-cell-based immunotherapies against cancer, which leverage this mechanism, can greatly benefit from structural analyses of pMHC complexes. Several attempts have been made to use molecular docking for such analyses, but pMHC structure remains too challenging for even state-of-the-art docking tools. To overcome these limitations, we describe the use of an incremental meta-docking approach for structural prediction of pMHC complexes. Previous methods applied in this context used specific constraints to reduce the complexity of this prediction problem, at the expense of generality. Our strategy makes no assumption and can potentially be used to predict binding modes for any pMHC complex. Our method has been tested in a re-docking experiment, reproducing the binding modes of 25 pMHC complexes whose crystal structures are available. This study is a proof of concept that incremental docking strategies can lead to general geometry prediction of pMHC complexes, with potential applications for immunotherapy against cancer or infectious diseases.",2018 Mar 12,"['Antunes, Dinler A.', 'Devaurs, Didier', 'Moll, Mark', 'Lizée, Gregory', 'Kavraki, Lydia E.']",Sci Rep,,,True
df2491bf73b3224ca6018e8f7cb2242e633e636c,PMC,Experience of 16 years and its associated challenges in the Field Epidemiology Training Program in Korea,http://dx.doi.org/10.4178/epih.e2017058,PMC5847970,29370686,CC BY,"OBJECTIVES: The field epidemiologist system of South Korea, which employs public health doctors who are relatively more readily available, was created in 1999 to ensure a ready supply of experts for epidemiological investigations and enable an effective response for new and reemerging infectious diseases. However, the 2015 outbreak of Middle East Respiratory Syndrome revealed limitations in the existing systems of management of field epidemiologists and communicable diseases. METHODS: The present study aims to evaluate data on current states, administrative reports, and other literature on the field epidemiologist system that has been in place in South Korea for 16 years since 1999 and to suggest appropriate future improvements in this system. RESULTS: By suggesting methods to evaluate the field epidemiologist system and training programs and by suggesting ways for the Korea Centers for Disease Control and Prevention to conduct evaluations on its own, the present study provides supporting evidence for improvement of systems for training of experts in epidemiological investigations. Moreover, based on the findings, this study also suggests methods to systematically train experts in communicable diseases management and a sustainable system to establish the basis of and develop strategies for a systematic and phased management of field epidemiologist training programs. CONCLUSIONS: The present study suggests the possibility of establishing dedicated training facilities, revising the guidelines on training and improvement of the competency of public health experts, while not limiting the scope of application to communicable diseases.",2017 Dec 25,"['Lee, Moo-Sik', 'Kim, Eun-Young', 'Lee, Sang-Won']",Epidemiol Health,,,True
c0bba2814eb6c6e6af25662fc57b78b04d471191,PMC,Experience of 16 years and its associated challenges in the Field Epidemiology Training Program in Korea,http://dx.doi.org/10.4178/epih.e2017058,PMC5847970,29370686,CC BY,"OBJECTIVES: The field epidemiologist system of South Korea, which employs public health doctors who are relatively more readily available, was created in 1999 to ensure a ready supply of experts for epidemiological investigations and enable an effective response for new and reemerging infectious diseases. However, the 2015 outbreak of Middle East Respiratory Syndrome revealed limitations in the existing systems of management of field epidemiologists and communicable diseases. METHODS: The present study aims to evaluate data on current states, administrative reports, and other literature on the field epidemiologist system that has been in place in South Korea for 16 years since 1999 and to suggest appropriate future improvements in this system. RESULTS: By suggesting methods to evaluate the field epidemiologist system and training programs and by suggesting ways for the Korea Centers for Disease Control and Prevention to conduct evaluations on its own, the present study provides supporting evidence for improvement of systems for training of experts in epidemiological investigations. Moreover, based on the findings, this study also suggests methods to systematically train experts in communicable diseases management and a sustainable system to establish the basis of and develop strategies for a systematic and phased management of field epidemiologist training programs. CONCLUSIONS: The present study suggests the possibility of establishing dedicated training facilities, revising the guidelines on training and improvement of the competency of public health experts, while not limiting the scope of application to communicable diseases.",2017 Dec 25,"['Lee, Moo-Sik', 'Kim, Eun-Young', 'Lee, Sang-Won']",Epidemiol Health,,,True
f9d40df8555bd7f3d0269178141f9e5ce11c6e2e,PMC,Infection Prevention and Control in Asia: Current Evidence and Future Milestones,http://dx.doi.org/10.1093/cid/cix071,PMC5848367,28475784,CC BY,,2017 May 15,"['Apisarnthanarak, Anucha', 'Mundy, Linda M', 'Tantawichien, Terapong', 'Leelarasamee, Amorn']",Clin Infect Dis,,,True
bf5c0b8c4f555f2af2ff41bc32faeb9c991dcafa,PMC,Microarray analysis of long non-coding RNA expression profiles uncovers a Toxoplasma-induced negative regulation of host immune signaling,http://dx.doi.org/10.1186/s13071-018-2697-8,PMC5848448,29530077,CC BY,"BACKGROUND: Toxoplasma gondii is an obligate intracellular protozoan parasite that can infect mammalian cells and thereby regulate host gene expression. The long non-coding RNAs (lncRNAs) have been demonstrated to be an important class of RNA molecules that regulate many biological processes, including host-pathogen interactions. However, the role of host lncRNAs in the response to T. gondii infection remains largely unknown. METHODS: We applied a microarray approach to determine the differential expression profiles of both lncRNAs and mRNAs in the human foreskin fibroblast (HFF) cells after T. gondii infection. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to reveal the potential functions of T. gondii-induced genes. Based on the co-expression networks of lncRNAs and immune-related genes, the role of NONSHAT022487 on the regulation of UNC93B1 related immune signaling was investigated by the knockdown and over-expression of lncRNA in human macrophage derived from the PMA-induced promonocytic cell line THP-1. RESULTS: Our data showed that 996 lncRNAs and 109 mRNAs in HFF cells were significantly and differentially expressed following T. gondii infection (fold change ≥ 5, P < 0.05). The results from the GO and KEGG pathway analyses indicated that the mRNAs with differential expression were mainly involved in the host immune response. Remarkably, we identified a novel lncRNA, NONSHAT022487, which suppresses the expression of the immune-related molecule UNC93B1. After T. gondii infection, NONSHAT022487 impaired the secretion of the cytokines IL-12, TNF-α, IL-1β and IFN-γ by downregulating UNC93B1 expression in human macrophage cells. CONCLUSIONS: Our study identified infection-induced lncRNA expression as a novel mechanism by which the Toxoplasma parasite regulates host immune signaling, which advances our understanding of the interaction of T. gondii parasites and host cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-018-2697-8) contains supplementary material, which is available to authorized users.",2018 Mar 12,"['Liu, Wenquan', 'Huang, Liyang', 'Wei, Qimei', 'Zhang, Yu', 'Zhang, Shengnan', 'Zhang, Wenting', 'Cai, Liya', 'Liang, Shaohui']",Parasit Vectors,,,True
b8fecbc5515e46b4dd16b9e11b4b1ce9a576e6d7,PMC,The use of complementary and alternative medicine by patients with cancer: a cross-sectional survey in Saudi Arabia,http://dx.doi.org/10.1186/s12906-018-2150-8,PMC5848536,29530034,CC BY,"BACKGROUND: A significant proportion of cancer patients use complementary and alternative medicine (CAM) along with conventional therapies (CT), whereas a smaller proportion delay or defer CT in favor of CAM. Previous studies exploring CAM use among cancer patients in the Middle East region have shown discrepant results. This study investigates the prevalence and pattern of CAM use by Saudi cancer patients. It also discusses the possible benefits and harm related to CAM use by cancer patients, and it explores the beliefs patients hold and their transparency with health care providers regarding their CAM use. METHODS: A cross-sectional study was conducted in oncology wards and outpatient clinics by using face-to-face interviews with the participants. RESULTS: A total of 156 patients with a median age of 50 years (18–84) participated in the study. The prevalence of CAM use was 69.9%; the most prominent types of CAM were those of a religious nature, such as supplication (95.4%), Quran recitation (88.1%), consuming Zamzam water (84.4%), and water upon which the Quran has been read (63.3%). Drinking camel milk was reported by 24.1% of CAM users, whereas camel urine was consumed by 15.7%. A variety of reasons were given for CAM use: 75% reported that they were using CAM to treat cancer, enhance mood (18.3%),control pain (11.9%), enhance the immune system (11%),increase physical fitness (6.4%), and improve appetite (4.6%). Thirty percent of CAM users had discussed the issue with their doctors; only 7.7% had done so with their nurses. CONCLUSIONS: The use of CAM, including camel products, is highly prevalent among cancer patients in the Middle East, but these patients do not necessarily divulge their CAM use to their treating physicians and nurses. Although CAM use can be beneficial, some can be very harmful, especially for cancer patients. Association is known between camel products and brucellosis and Middle East respiratory syndrome coronavirus (MERS-CoV). Both can lead to tremendous morbidity in immune-compromised patients. Doctor–patient communication regarding CAM use is of paramount importance in cancer care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12906-018-2150-8) contains supplementary material, which is available to authorized users.",2018 Mar 12,"['Abuelgasim, Khadega A.', 'Alsharhan, Yousef', 'Alenzi, Tariq', 'Alhazzani, Abdulaziz', 'Ali, Yosra Z.', 'Jazieh, Abdul Rahman']",BMC Complement Altern Med,,,True
b91ed425c419f49767c9f34f131392969261d5ce,PMC,Epidemiologic analysis of respiratory viral infections among Singapore military servicemen in 2016,http://dx.doi.org/10.1186/s12879-018-3040-x,PMC5848554,29529993,CC BY,"BACKGROUND: Respiratory illnesses have been identified as a significant factor leading to lost training time and morbidity among Singapore military recruits. A surveillance programme has been put in place to determine etiological agents responsible for febrile, as well as afebrile respiratory illnesses in a military camp. The goal of the study is to better understand the epidemiology of these diseases and identify potential countermeasures to protect military recruits against them. METHODS: From Jan 2016 - Jan 2017, a total of 2647 respiratory cases were enrolled into the surveillance programme. The cases were further stratified into Febrile Respiratory Illness (FRI, with body temperature > 37.5 °C) or Acute Respiratory Illness (ARI, with body temperature < 37.5 °C). Nasal washes were collected and tested by multiplex PCR to detect 26 different pathogens. RESULTS: One thousand ninety five cases (41% of total cases) met the criteria of FRI in which 932 cases (85% of FRI cases) were screened positive for at least one virus. The most common etiological agents for FRI mono-infection cases were Adenovirus E and Rhinovirus. Recruits infected with H3N2 influenza, Influenza B and Adenovirus E viruses were most likely presented as FRI cases. Notably, H3N2 influenza resulted in the greatest rise in body temperature. The remaining 1552 cases (59% of total cases) met the criteria of ARI in which 1198 cases (77% of ARI cases) were screened positive for at least one virus. The most common etiological agent for ARI mono-infection was Rhinovirus. The distribution pattern for dual infections was different for ARI and FRI cases. Maximum number of pathogens detected in a sample was five for both groups. CONCLUSION: Previous studies on respiratory diseases in military focused largely on FRI cases. With the expanded surveillance to ARI cases, this study allows unbiased evaluation of the impact of respiratory disease pathogens among recruits in a military environment. The results show that several pathogens have a much bigger role in causing respiratory diseases in this cohort. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3040-x) contains supplementary material, which is available to authorized users.",2018 Mar 12,"['Lau, Yuk-Fai', 'Koh, Wee-Hong Victor', 'Kan, Clement', 'Dua, Poh-Choo Alethea', 'Lim, Ai-Sim Elizabeth', 'Liaw, Chin-Wen Jasper', 'Gao, Qiu-Han', 'Chng, Jeremiah', 'Lee, Vernon J.', 'Tan, Boon-Huan', 'Loh, Jin-Phang']",BMC Infect Dis,,,False
3031e9b7e020609a6d9d2982a41779692a6761b0,PMC,Epidemiologic analysis of respiratory viral infections among Singapore military servicemen in 2016,http://dx.doi.org/10.1186/s12879-018-3040-x,PMC5848554,29529993,CC BY,"BACKGROUND: Respiratory illnesses have been identified as a significant factor leading to lost training time and morbidity among Singapore military recruits. A surveillance programme has been put in place to determine etiological agents responsible for febrile, as well as afebrile respiratory illnesses in a military camp. The goal of the study is to better understand the epidemiology of these diseases and identify potential countermeasures to protect military recruits against them. METHODS: From Jan 2016 - Jan 2017, a total of 2647 respiratory cases were enrolled into the surveillance programme. The cases were further stratified into Febrile Respiratory Illness (FRI, with body temperature > 37.5 °C) or Acute Respiratory Illness (ARI, with body temperature < 37.5 °C). Nasal washes were collected and tested by multiplex PCR to detect 26 different pathogens. RESULTS: One thousand ninety five cases (41% of total cases) met the criteria of FRI in which 932 cases (85% of FRI cases) were screened positive for at least one virus. The most common etiological agents for FRI mono-infection cases were Adenovirus E and Rhinovirus. Recruits infected with H3N2 influenza, Influenza B and Adenovirus E viruses were most likely presented as FRI cases. Notably, H3N2 influenza resulted in the greatest rise in body temperature. The remaining 1552 cases (59% of total cases) met the criteria of ARI in which 1198 cases (77% of ARI cases) were screened positive for at least one virus. The most common etiological agent for ARI mono-infection was Rhinovirus. The distribution pattern for dual infections was different for ARI and FRI cases. Maximum number of pathogens detected in a sample was five for both groups. CONCLUSION: Previous studies on respiratory diseases in military focused largely on FRI cases. With the expanded surveillance to ARI cases, this study allows unbiased evaluation of the impact of respiratory disease pathogens among recruits in a military environment. The results show that several pathogens have a much bigger role in causing respiratory diseases in this cohort. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3040-x) contains supplementary material, which is available to authorized users.",2018 Mar 12,"['Lau, Yuk-Fai', 'Koh, Wee-Hong Victor', 'Kan, Clement', 'Dua, Poh-Choo Alethea', 'Lim, Ai-Sim Elizabeth', 'Liaw, Chin-Wen Jasper', 'Gao, Qiu-Han', 'Chng, Jeremiah', 'Lee, Vernon J.', 'Tan, Boon-Huan', 'Loh, Jin-Phang']",BMC Infect Dis,,,False
1ff255719ae770ac447902320cf19bd3c7e895b7,PMC,Epidemiologic analysis of respiratory viral infections among Singapore military servicemen in 2016,http://dx.doi.org/10.1186/s12879-018-3040-x,PMC5848554,29529993,CC BY,"BACKGROUND: Respiratory illnesses have been identified as a significant factor leading to lost training time and morbidity among Singapore military recruits. A surveillance programme has been put in place to determine etiological agents responsible for febrile, as well as afebrile respiratory illnesses in a military camp. The goal of the study is to better understand the epidemiology of these diseases and identify potential countermeasures to protect military recruits against them. METHODS: From Jan 2016 - Jan 2017, a total of 2647 respiratory cases were enrolled into the surveillance programme. The cases were further stratified into Febrile Respiratory Illness (FRI, with body temperature > 37.5 °C) or Acute Respiratory Illness (ARI, with body temperature < 37.5 °C). Nasal washes were collected and tested by multiplex PCR to detect 26 different pathogens. RESULTS: One thousand ninety five cases (41% of total cases) met the criteria of FRI in which 932 cases (85% of FRI cases) were screened positive for at least one virus. The most common etiological agents for FRI mono-infection cases were Adenovirus E and Rhinovirus. Recruits infected with H3N2 influenza, Influenza B and Adenovirus E viruses were most likely presented as FRI cases. Notably, H3N2 influenza resulted in the greatest rise in body temperature. The remaining 1552 cases (59% of total cases) met the criteria of ARI in which 1198 cases (77% of ARI cases) were screened positive for at least one virus. The most common etiological agent for ARI mono-infection was Rhinovirus. The distribution pattern for dual infections was different for ARI and FRI cases. Maximum number of pathogens detected in a sample was five for both groups. CONCLUSION: Previous studies on respiratory diseases in military focused largely on FRI cases. With the expanded surveillance to ARI cases, this study allows unbiased evaluation of the impact of respiratory disease pathogens among recruits in a military environment. The results show that several pathogens have a much bigger role in causing respiratory diseases in this cohort. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3040-x) contains supplementary material, which is available to authorized users.",2018 Mar 12,"['Lau, Yuk-Fai', 'Koh, Wee-Hong Victor', 'Kan, Clement', 'Dua, Poh-Choo Alethea', 'Lim, Ai-Sim Elizabeth', 'Liaw, Chin-Wen Jasper', 'Gao, Qiu-Han', 'Chng, Jeremiah', 'Lee, Vernon J.', 'Tan, Boon-Huan', 'Loh, Jin-Phang']",BMC Infect Dis,,,True
89d27a03696c2c515c9477eb696580d6041835e0,PMC,Asymmetric expression level of clock genes in left vs. right nasal mucosa in humans with and without allergies and in rats: Circadian characteristics and possible contribution to nasal cycle,http://dx.doi.org/10.1371/journal.pone.0194018,PMC5849312,29534090,CC BY,"Numerous peripheral tissues possess self-sustaining daily biologic rhythms that are regulated at the molecular level by clock genes such as PER1, PER2, CLOCK, and BMAL1. Physiological function of nasal mucosa exhibits rhythmic variability to a day-night environmental cycle. Nevertheless, little is known of the expression and distribution pattern of clock genes in nasal mucosa. The present study investigates the expression level and distribution pattern of PER1, PER2, CLOCK, and BMAL1 genes in nasal mucosa of healthy controls, allergic rhinitis patients, and normal rats. In human and rat nasal mucosa, the levels of these genes are asymmetrically expressed in nasal mucosa derived from right and left cavities in normal controls, allergic patients, and rat. In human nasal mucosa, the expression levels of these genes were higher in the decongested side than the congested mucosa. In rat nasal mucosa, these clock genes are expressed in a rhythmic circadian manner under the regular light/dark cycles. The expression levels of MUC5AC, a key mucin genes produced in superficial epithelium, are higher in decongested side than that congested side in human nasal mucosa. In rat nasal mucosa, MUC5AC levels showed a circadian rhythm which was associated with different expression levels in nasal mucosa derived from the right and left nasal cavities. Taken together with these results, the present study shows that the clock genes such as PER1, PER2, CLOCK, and BMAL1 are present in human and rat nasal mucosa, and suggest that these clock genes may control the pathophysiological function of nasal mucosa as circadian oscillators and affect the maintenance of the nasal cycle.",2018 Mar 13,"['Kim, Ha Kyun', 'Kim, Hyun Jung', 'Kim, Jae Hyung', 'Kim, Tae Hoon', 'Lee, Sang Hag']",PLoS One,,,True
e31f9523d25a534a48452c6d78bd02b9c0222bca,PMC,Translating Lung Microbiome Profiles into the Next-Generation Diagnostic Gold Standard for Pneumonia: a Clinical Investigator’s Perspective,http://dx.doi.org/10.1128/mSystems.00153-17,PMC5850077,29556537,CC BY,"Severe bacterial pneumonia is a major global cause of morbidity and mortality, yet current diagnostic approaches rely on identification of causative pathogens by cultures, which require extended incubation periods and often fail to detect relevant pathogens. Consequently, patients are prescribed broad-spectrum antibiotics in a “one-size-fits-all” manner, which may be inappropriate for their individual needs and promote antibiotic resistance. My research focuses on leveraging next-generation sequencing of microbial DNA directly from patient samples for the development of new, culture-independent definitions of pneumonia. In this perspective article, I discuss the current state of the field and focus on the conceptual and research design challenges for clinical translation. With ongoing technological advancements and application of computational biology methods for assessing clinical validity and utility, I anticipate that sequencing-based diagnostics will soon be able to positively disrupt the way we think about, diagnose, and treat pulmonary infections.",2018 Mar 13,"Kitsios, Georgios D.",mSystems,,,True
8171299fc5073dfe98c4c56d5760ccb5f802f8f0,PMC,Adenine Enrichment at the Fourth CDS Residue in Bacterial Genes Is Consistent with Error Proofing for +1 Frameshifts,http://dx.doi.org/10.1093/molbev/msx223,PMC5850271,28961919,CC BY,"Beyond selection for optimal protein functioning, coding sequences (CDSs) are under selection at the RNA and DNA levels. Here, we identify a possible signature of “dual-coding,” namely extensive adenine (A) enrichment at bacterial CDS fourth sites. In 99.07% of studied bacterial genomes, fourth site A use is greater than expected given genomic A-starting codon use. Arguing for nucleotide level selection, A-starting serine and arginine second codons are heavily utilized when compared with their non-A starting synonyms. Several models have the ability to explain some of this trend. In part, A-enrichment likely reduces 5′ mRNA stability, promoting translation initiation. However T/U, which may also reduce stability, is avoided. Further, +1 frameshifts on the initiating ATG encode a stop codon (TGA) provided A is the fourth residue, acting either as a frameshift “catch and destroy” or a frameshift stop and adjust mechanism and hence implicated in translation initiation. Consistent with both, genomes lacking TGA stop codons exhibit weaker fourth site A-enrichment. Sequences lacking a Shine–Dalgarno sequence and those without upstream leader genes, that may be more error prone during initiation, have greater utilization of A, again suggesting a role in initiation. The frameshift correction model is consistent with the notion that many genomic features are error-mitigation factors and provides the first evidence for site-specific out of frame stop codon selection. We conjecture that the NTG universal start codon may have evolved as a consequence of TGA being a stop codon and the ability of NTGA to rapidly terminate or adjust a ribosome.",2017 Dec 24,"['Abrahams, Liam', 'Hurst, Laurence D']",Mol Biol Evol,,,True
bbcb78719cba8e781ca99c3069823e9270053ac3,PMC,Structural and Functional Basis of the Fidelity of Nucleotide Selection by Flavivirus RNA-Dependent RNA Polymerases,http://dx.doi.org/10.3390/v10020059,PMC5850366,29385764,CC BY,"Viral RNA-dependent RNA polymerases (RdRps) play a central role not only in viral replication, but also in the genetic evolution of viral RNAs. After binding to an RNA template and selecting 5′-triphosphate ribonucleosides, viral RdRps synthesize an RNA copy according to Watson-Crick base-pairing rules. The copy process sometimes deviates from both the base-pairing rules specified by the template and the natural ribose selectivity and, thus, the process is error-prone due to the intrinsic (in)fidelity of viral RdRps. These enzymes share a number of conserved amino-acid sequence strings, called motifs A–G, which can be defined from a structural and functional point-of-view. A co-relation is gradually emerging between mutations in these motifs and viral genome evolution or observed mutation rates. Here, we review our current knowledge on these motifs and their role on the structural and mechanistic basis of the fidelity of nucleotide selection and RNA synthesis by Flavivirus RdRps.",2018 Jan 30,"['Selisko, Barbara', 'Papageorgiou, Nicolas', 'Ferron, François', 'Canard, Bruno']",Viruses,,,True
7c693ae9e08e10d9c230c3d00ad7c6612fa13631,PMC,Mammarenaviral Infection Is Dependent on Directional Exposure to and Release from Polarized Intestinal Epithelia,http://dx.doi.org/10.3390/v10020075,PMC5850382,29439402,CC BY,"Mammarenavirusesare single-stranded RNA viruses with a bisegmented ambisense genome. Ingestion has been shown as a natural route of transmission for both Lassa virus (LASV) and Lymphocytic choriomeningitis virus (LCMV). Due to the mechanism of transmission, epithelial tissues are among the first host cells to come in contact with the viruses, and as such they potentially play a role in spread of virus to naïve hosts. The role of the intestinal epithelia during arenavirus infection remains to be uncharacterized. We have utilized a well-established cell culture model, Caco-2, to investigate the role of intestinal epithelia during intragastric infection. We found that LCMV-Armstrong, LCMV-WE, and Mopeia (MOPV) release infectious progeny via similar patterns. However, the reassortant virus, ML-29, containing the L segment of MOPV and S segment of LASV, exhibits a unique pattern of viral release relative to LCMV and MOPV. Furthermore, we have determined attachment efficacy to Caco-2 cells is potentially responsible for observed replication kinetics of these viruses in a polarized Caco-2 cell model. Collectively, our data shows that viral dissemination and interaction with intestinal epithelia may be host, tissue, and viral specific.",2018 Feb 10,"['Warner, Nikole L.', 'Jokinen, Jenny D.', 'Beier, Juliane I.', 'Sokoloski, Kevin J.', 'Lukashevich, Igor S.']",Viruses,,,True
1628fb770b782044ef43a9c63252b5d3b25a38ba,PMC,MERS-CoV: Understanding the Latest Human Coronavirus Threat,http://dx.doi.org/10.3390/v10020093,PMC5850400,29495250,CC BY,"Human coronaviruses cause both upper and lower respiratory tract infections in humans. In 2012, a sixth human coronavirus (hCoV) was isolated from a patient presenting with severe respiratory illness. The 60-year-old man died as a result of renal and respiratory failure after admission to a hospital in Jeddah, Saudi Arabia. The aetiological agent was eventually identified as a coronavirus and designated Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV has now been reported in more than 27 countries across the Middle East, Europe, North Africa and Asia. As of July 2017, 2040 MERS-CoV laboratory confirmed cases, resulting in 712 deaths, were reported globally, with a majority of these cases from the Arabian Peninsula. This review summarises the current understanding of MERS-CoV, with special reference to the (i) genome structure; (ii) clinical features; (iii) diagnosis of infection; and (iv) treatment and vaccine development.",2018 Feb 24,"['Chafekar, Aasiyah', 'Fielding, Burtram C.']",Viruses,,,True
4208f9c98e378d4959debc3ba361e9cc6972e814,PMC,Dynamic network measures reveal the impact of cattle markets and alpine summering on the risk of epidemic outbreaks in the Swiss cattle population,http://dx.doi.org/10.1186/s12917-018-1406-3,PMC5851077,29534711,CC BY,"BACKGROUND: Livestock herds are interconnected with each other via an intricate network of transports of animals which represents a potential substrate for the spread of epidemic diseases. We analysed four years (2012–2015) of daily bovine transports to assess the risk of disease transmission and identify times and locations where monitoring would be most effective. Specifically, we investigated how the seasonal dynamics of transport networks, driven by the alpine summering and traditional cattle markets, affect the risk of epidemic outbreaks. RESULTS: We found strong and consistent seasonal variation in several structural network measures as well as in measures for outbreak risk. Analysis of the consequences of excluding markets, dealers and alpine pastures from the network shows that markets contribute much more to the overall outbreak risk than alpine summering. Static descriptors of monthly transport networks were poor predictors of outbreak risk emanating from individual holdings; a dynamic measure, which takes the temporal structure of the network into account, gave better risk estimates. A stochastic simulation suggests that targeted surveillance based on this dynamic network allows a higher detection rate and smaller outbreak size at detection than compared to other sampling schemes. CONCLUSIONS: Dynamic measures based on time-stamped data—the outgoing contact chain—can give better risk estimates and could help to improve surveillance schemes. Using this measure we find evidence that even in a country with intense summering practice, markets continue being the prime risk factor for the spread of contagious diseases.",2018 Mar 13,"['Vidondo, Beatriz', 'Voelkl, Bernhard']",BMC Vet Res,,,True
70501576998f6532d594f5f7198b7473bc55a32a,PMC,Molecular characterization of US-like and Asian non-S INDEL strains of porcine epidemic diarrhea virus (PEDV) that circulated in Japan during 2013–2016 and PEDVs collected from recurrent outbreaks,http://dx.doi.org/10.1186/s12917-018-1409-0,PMC5852955,29540176,CC BY,"BACKGROUND: Since late 2013, porcine epidemic diarrhea virus (PEDV) has reemerged in Japan and caused severe economic losses to the swine industry. Although PEDV vaccines have been used widely, the disease has swept rapidly across the county, and is commonly observed in PED-vaccinated farms, and has recurred in domestic herds. To better understand PEDVs responsible for the reemerging outbreaks in Japan, full-length spike (S), membrane (M), and nucleocapsid (N) genes of 45 PEDVs collected in Japan during 2013–2016, were sequenced and analyzed. RESULTS: Phylogenetic analysis based on S gene sequences revealed that all the recent field PEDVs were genetically distinct from the classical Japanese strains, and were classified into three genotypes: North American (NA), S INDEL, and Asian non-S INDEL. Our data suggested a possibility that multiple parental PEDV strains were introduced into Japan from abroad at the same time or similar times. The newly identified Japanese strains showed the closest relationship to the US strains. Two sublineages of Japanese strains circulating in Japan were similar to two sublineages identified in the US, suggesting common ancestors for these strains. In comparison with two vaccine strains used in Japan, the field strains had various changes in epitope regions, glycosylation sites, and phosphorylation sites. These substitutions, particularly observed in epitope regions of the S (521, 553, 568, and 570), M (5), and N (123, 252, and 255) proteins, may have affected antigenicity and vaccine efficacy, resulting in an unsuccessful PEDV control. Sequence comparisons between PEDVs collected from primary and secondary outbreaks in three herds revealed that the disease has developed to an endemic stage in which PEDV could persist for nearly two years in the herds or local regions, causing subsequent epidemics. CONCLUSIONS: These results elucidate the genetic characteristics, origin, and molecular epidemiology of PEDVs circulating in Japan, as well as the PEDV strains causing recurrent outbreaks. This study provides a better insight into the PEDVs responsible for recent outbreaks in Japan, and could potentially help to develop measures for controlling and preventing the disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1409-0) contains supplementary material, which is available to authorized users.",2018 Mar 14,"['Van Diep, Nguyen', 'Sueyoshi, Masuo', 'Norimine, Junzo', 'Hirai, Takuya', 'Myint, Ohnmar', 'Teh, Angeline Ping Ping', 'Izzati, Uda Zahli', 'Fuke, Naoyuki', 'Yamaguchi, Ryoji']",BMC Vet Res,,,False
4c2d326a10d98f8f503f8df460291e059cc77a75,PMC,Molecular characterization of US-like and Asian non-S INDEL strains of porcine epidemic diarrhea virus (PEDV) that circulated in Japan during 2013–2016 and PEDVs collected from recurrent outbreaks,http://dx.doi.org/10.1186/s12917-018-1409-0,PMC5852955,29540176,CC BY,"BACKGROUND: Since late 2013, porcine epidemic diarrhea virus (PEDV) has reemerged in Japan and caused severe economic losses to the swine industry. Although PEDV vaccines have been used widely, the disease has swept rapidly across the county, and is commonly observed in PED-vaccinated farms, and has recurred in domestic herds. To better understand PEDVs responsible for the reemerging outbreaks in Japan, full-length spike (S), membrane (M), and nucleocapsid (N) genes of 45 PEDVs collected in Japan during 2013–2016, were sequenced and analyzed. RESULTS: Phylogenetic analysis based on S gene sequences revealed that all the recent field PEDVs were genetically distinct from the classical Japanese strains, and were classified into three genotypes: North American (NA), S INDEL, and Asian non-S INDEL. Our data suggested a possibility that multiple parental PEDV strains were introduced into Japan from abroad at the same time or similar times. The newly identified Japanese strains showed the closest relationship to the US strains. Two sublineages of Japanese strains circulating in Japan were similar to two sublineages identified in the US, suggesting common ancestors for these strains. In comparison with two vaccine strains used in Japan, the field strains had various changes in epitope regions, glycosylation sites, and phosphorylation sites. These substitutions, particularly observed in epitope regions of the S (521, 553, 568, and 570), M (5), and N (123, 252, and 255) proteins, may have affected antigenicity and vaccine efficacy, resulting in an unsuccessful PEDV control. Sequence comparisons between PEDVs collected from primary and secondary outbreaks in three herds revealed that the disease has developed to an endemic stage in which PEDV could persist for nearly two years in the herds or local regions, causing subsequent epidemics. CONCLUSIONS: These results elucidate the genetic characteristics, origin, and molecular epidemiology of PEDVs circulating in Japan, as well as the PEDV strains causing recurrent outbreaks. This study provides a better insight into the PEDVs responsible for recent outbreaks in Japan, and could potentially help to develop measures for controlling and preventing the disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1409-0) contains supplementary material, which is available to authorized users.",2018 Mar 14,"['Van Diep, Nguyen', 'Sueyoshi, Masuo', 'Norimine, Junzo', 'Hirai, Takuya', 'Myint, Ohnmar', 'Teh, Angeline Ping Ping', 'Izzati, Uda Zahli', 'Fuke, Naoyuki', 'Yamaguchi, Ryoji']",BMC Vet Res,,,True
e42c06c072d59a6eb0f4ae89f74cc4f4689644b7,PMC,Hypothalamus-pituitary-adrenal axis involves in anti-viral ability through regulation of immune response in piglets infected by highly pathogenic porcine reproductive and respiratory syndrome virus,http://dx.doi.org/10.1186/s12917-018-1414-3,PMC5853143,29540178,CC BY,"BACKGROUND: The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has been responsible for several viral attacks in the Asian porcine industry, since the first outbreak in China in 2006. During the early stages of the HP-PRRSV infection, high levels of proinflammatory cytokines are noted in the host peripheral blood, which are accompanied by severe lesions in the lungs and immune system organs; these are considered as the greatest contributors to the overall disease burden. We hypothesized that the anti-PRRSV response in piglets might be mediated by the hypothalamus-pituitary-adrenal (HPA) axis, which led to a decrease in the psycho-neuroendocrinological manifestation of HP-PRRSV etiology via immune response regulation. RESULTS: We investigated the regulation of the HPA axis in HP-PRRSV-infected piglets that were treated with 1 mg/kg body weight (b. w.)/day mifepristone (RU486) or 2 mg/kg b.w./day dexamethasone (DEX). Both RU486 and DEX enhanced the disease status of the piglets infected by the HP-PRRSV HuN4 strain, resulting in high mortality and more severe pathological changes in the lungs. CONCLUSIONS: HP-PRRSV infection activates the HPA axis, and artificial regulation of the immune-endocrine system enhances disease severity in HP-PRRSV-infected piglets. Thus, DEX and RU486 should be avoided in the clinical treatment of HP-PRRS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1414-3) contains supplementary material, which is available to authorized users.",2018 Mar 14,"['Tong, Jie', 'Yu, Ying', 'Zheng, Linlin', 'Zhang, Chong', 'Tu, Yabin', 'Liu, Yonggang', 'Wu, Jianan', 'Li, Hai', 'Wang, Shujie', 'Jiang, Chenggang', 'Zhou, En-Min', 'Wang, Gang', 'Cai, Xuehui']",BMC Vet Res,,,True
01285aff189f375f52b762256d8f419ccad3077c,PMC,Lessons From the Polio Endgame: Overcoming the Failure to Vaccinate and the Role of Subpopulations in Maintaining Transmission,http://dx.doi.org/10.1093/infdis/jix108,PMC5853387,28838194,CC BY,"BACKGROUND. Recent detections of circulating serotype 2 vaccine-derived poliovirus in northern Nigeria (Borno and Sokoto states) and Pakistan (Balochistan Province) and serotype 1 wild poliovirus in Pakistan, Afghanistan, and Nigeria (Borno) represent public health emergencies that require aggressive response. METHODS. We demonstrate the importance of undervaccinated subpopulations, using an existing dynamic poliovirus transmission and oral poliovirus vaccine evolution model. We review the lessons learned during the polio endgame about the role of subpopulations in sustaining transmission, and we explore the implications of subpopulations for other vaccine-preventable disease eradication efforts. RESULTS. Relatively isolated subpopulations benefit little from high surrounding population immunity to transmission and will sustain transmission as long as they do not attain high vaccination coverage. Failing to reach such subpopulations with high coverage represents the root cause of polio eradication delays. Achieving and maintaining eradication requires addressing the weakest links, which includes immunizing populations in insecure areas and/or with disrupted or poor-performing health systems and managing the risks of individuals with primary immunodeficiencies who can excrete vaccine-derived poliovirus long-term. CONCLUSIONS. Eradication efforts for vaccine-preventable diseases need to create performance expectations for countries to immunize all people living within their borders and maintain high coverage with appropriate interventions.Keywords. Polio; eradication; transmission; heterogeneity.",2017 Jul 1,"['Thompson, Kimberly M.', 'Duintjer Tebbens, Radboud J.']",J Infect Dis,,,True
2e3c6d9e2a2a8d2d9b43d5ae7b882c9a82557274,PMC,"Ebola Virus Neutralizing Antibodies Detectable in Survivors of theYambuku, Zaire Outbreak 40 Years after Infection",http://dx.doi.org/10.1093/infdis/jix584,PMC5853670,29253164,CC BY,"The first reported outbreak of Ebola virus disease occurred in 1976 in Yambuku, Democratic Republic of Congo. Antibody responses in survivors 11 years after infection have been documented. However, this report is the first characterization of anti-Ebola virus antibody persistence and neutralization capacity 40 years after infection. Using ELISAs we measured survivor’s immunological response to Ebola virus Zaire (EBOV) glycoprotein and nucleoprotein, and assessed VP40 reactivity. Neutralization of EBOV was measured using a pseudovirus approach and plaque reduction neutralization test with live EBOV. Some survivors from the original EBOV outbreak still harbor antibodies against all 3 measures. Interestingly, a subset of these survivors’ serum antibodies could still neutralize live virus 40 years postinitial infection. These data provide the longest documentation of both anti-Ebola serological response and neutralization capacity within any survivor cohort, extending the known duration of response from 11 years postinfection to at least 40 years after symptomatic infection.",2018 Jan 15,"['Rimoin, Anne W', 'Lu, Kai', 'Bramble, Matthew S', 'Steffen, Imke', 'Doshi, Reena H', 'Hoff, Nicole A', 'Mukadi, Patrick', 'Nicholson, Bradly P', 'Alfonso, Vivian H', 'Olinger, Gerrard', 'Sinai, Cyrus', 'Yamamoto, Lauren K', 'Ramirez, Christina M', 'Okitolonda Wemakoy, Emile', 'Kebela Illunga, Benoit', 'Pettitt, James', 'Logue, James', 'Bennett, Richard S', 'Jahrling, Peter', 'Heymann, David L', 'Piot, Peter', 'Muyembe-Tamfum, Jean Jacques', 'Hensley, Lisa E', 'Simmons, Graham']",J Infect Dis,,,True
8c6dd0cad7b723b44a8b557ca0f67d1ee38d88fb,PMC,A New Approach to Evaluating the Risk–Benefit Equation for Dual-Use and Gain-of-Function Research of Concern,http://dx.doi.org/10.3389/fbioe.2018.00021,PMC5853790,29568736,CC BY,"In the twenty-first century, biology faces a problem that has previously vexed other disciplines such as physics, namely the prospect that its knowledge domain could be used to generate biological agents with altered properties that enhanced their weapon potential. Biological weapons bring the additional dimension that these could be self-replicating, easy to manufacture and synthesized with commonly available expertise. This resulted in increasing concern about the type of research done and communicated, despite the fact that such research often has direct societal benefits, bringing the dual-use dilemma to biology. The conundrum of dual use research of concern was crystallized by the so-called “gain-of-function” type of experiments in which avian influenza viruses were endowed with new properties in the laboratory such as increased virulence and the capacity for mammalian transmission. After more than a decade of intensive discussion and controversy involving biological experiments with dual-use potential, there is no consensus on the issue except for the need to carry out such experiments in the safest conditions possible. In this essay, we review the topic with the hindsight of several years and suggest that instead of prescribing prohibitions and experimental limitations the focus should be on the importance of scientific questions at hand. We posit that the importance of a scientific question for medical and scientific progress provides a benchmark to determine the acceptable level of risk in biological experimentation.",2018 Mar 8,"['Imperiale, Michael J.', 'Casadevall, Arturo']",Front Bioeng Biotechnol,,,True
06d210540bbdfe3b898f2ffbc4d1f9fb74a5a4d8,PMC,Addressing the Challenges and Opportunities of the Polio Endgame: Lessons for the Future,http://dx.doi.org/10.1093/infdis/jix117,PMC5853839,28838196,CC BY,"The Global Commission for the Certification of the Eradication of Poliomyelitis certified the eradication of type 2 poliovirus in September 2015, making type 2 poliovirus the first human pathogen to be eradicated since smallpox. The eradication of type 2 poliovirus, the absence of detection of type 3 poliovirus worldwide since November 2012, and cornering type 1 poliovirus to only a few geographic areas of 3 countries has enabled implementation of the endgame of polio eradication which calls for a phased withdrawal of oral polio vaccine beginning with the type 2 component, introduction of inactivated poliovirus vaccine, strengthening of routine immunization in countries with extensive polio resources, and initiating activities to transition polio resources, program experience, and lessons learned to other global health initiatives. This supplement focuses on efforts by global partners to successfully launch polio endgame activities to permanently secure and sustain the enormous gains of polio eradication forever.",2017 Jul 1,"['Patel, Manish', 'Cochi, Stephen']",J Infect Dis,,,True
e9c971f80258e83c52a7e490ae2bf8af0e59e232,PMC,Chromogenic detection of yam mosaic virus by closed-tube reverse transcription loop-mediated isothermal amplification (CT-RT-LAMP),http://dx.doi.org/10.1007/s00705-018-3706-0,PMC5854734,29308543,CC BY,"A closed-tube reverse transcription loop-mediated isothermal amplification (CT-RT-LAMP) assay was developed for the detection of yam mosaic virus (YMV, genus Potyvirus) infecting yam (Dioscorea spp.). The assay uses a set of six oligonucleotide primers targeting the YMV coat protein region, and the amplification products in YMV-positive samples are visualized by chromogenic detection with SYBR Green I dye. The CT-RT-LAMP assay detected YMV in leaf and tuber tissues of infected plants. The assay is 100 times more sensitive in detecting YMV than standard RT-PCR, while maintaining the same specificity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-018-3706-0) contains supplementary material, which is available to authorized users.",2018 Jan 8,"['Nkere, Chukwuemeka K.', 'Oyekanmi, Joshua O.', 'Silva, Gonçalo', 'Bömer, Moritz', 'Atiri, Gabriel I.', 'Onyeka, Joseph', 'Maroya, Norbert G.', 'Seal, Susan E.', 'Kumar, P. Lava']",Arch Virol,,,True
18c1ceb51b621792118f18381b9b3606b46717a9,PMC,"Molecular Research on Emerging Viruses: Evolution, Diagnostics, Pathogenesis, and Therapeutics",http://dx.doi.org/10.3390/ijms19020398,PMC5855620,29385690,CC BY,,2018 Jan 30,"Lau, Susanna K. P.",Int J Mol Sci,,,True
e5ee01ea0acff01da191ffff2d9fbef2f9aebff7,PMC,Peptide-Based Membrane Fusion Inhibitors Targeting HCoV-229E Spike Protein HR1 and HR2 Domains,http://dx.doi.org/10.3390/ijms19020487,PMC5855709,29415501,CC BY,"Human coronavirus 229E (HCoV-229E) infection in infants, elderly people, and immunocompromised patients can cause severe disease, thus calling for the development of effective and safe therapeutics to treat it. Here we reported the design, synthesis and characterization of two peptide-based membrane fusion inhibitors targeting HCoV-229E spike protein heptad repeat 1 (HR1) and heptad repeat 2 (HR2) domains, 229E-HR1P and 229E-HR2P, respectively. We found that 229E-HR1P and 229E-HR2P could interact to form a stable six-helix bundle and inhibit HCoV-229E spike protein-mediated cell-cell fusion with IC(50) of 5.7 and 0.3 µM, respectively. 229E-HR2P effectively inhibited pseudotyped and live HCoV-229E infection with IC(50) of 0.5 and 1.7 µM, respectively. In a mouse model, 229E-HR2P administered intranasally could widely distribute in the upper and lower respiratory tracts and maintain its fusion-inhibitory activity. Therefore, 229E-HR2P is a promising candidate for further development as an antiviral agent for the treatment and prevention of HCoV-229E infection.",2018 Feb 6,"['Xia, Shuai', 'Xu, Wei', 'Wang, Qian', 'Wang, Cong', 'Hua, Chen', 'Li, Weihua', 'Lu, Lu', 'Jiang, Shibo']",Int J Mol Sci,,,True
61ab8b92a20e33291536d1b0ef49ca4657cd4b43,PMC,Mitochondrial Dynamics in Basal and Stressful Conditions,http://dx.doi.org/10.3390/ijms19020564,PMC5855786,29438347,CC BY,"The historical role of mitochondria resides in converting the energy released during the oxidation of macromolecules (carbohydrates, lipids and proteins) into adenosine tri-phosphate, a major form of chemically stored energy which sustains cell growth and homeostasis. Beyond this role in bioenergetics regulation, mitochondria play a role in several other cellular processes including lipid metabolism, cellular calcium homeostasis, autophagy and immune responses. Furthermore, mitochondria are highly dynamic organelles: as all other cellular endomembranes, they are continuously moving along cytoskeleton, and, most importantly, they constantly interact one with each other by membrane tethering, fusion and fission. This review aims to highlight the tight correlation between the morphodynamics of mitochondria and their biological function(s), in physiological as well as stress conditions, in particular nutrient deprivation, pathogen attack and some human diseases. Finally, we emphasize some crosstalk between the fusion/fission machinery and the autophagy pathway to ending on some speculative hypothesis to inspire future research in the field.",2018 Feb 13,"['Zemirli, Naima', 'Morel, Etienne', 'Molino, Diana']",Int J Mol Sci,,,True
540308d13f057351fc824202d89629e4748e2814,PMC,Mapping road network communities for guiding disease surveillance and control strategies,http://dx.doi.org/10.1038/s41598-018-22969-4,PMC5856805,29549364,CC BY,"Human mobility is increasing in its volume, speed and reach, leading to the movement and introduction of pathogens through infected travelers. An understanding of how areas are connected, the strength of these connections and how this translates into disease spread is valuable for planning surveillance and designing control and elimination strategies. While analyses have been undertaken to identify and map connectivity in global air, shipping and migration networks, such analyses have yet to be undertaken on the road networks that carry the vast majority of travellers in low and middle income settings. Here we present methods for identifying road connectivity communities, as well as mapping bridge areas between communities and key linkage routes. We apply these to Africa, and show how many highly-connected communities straddle national borders and when integrating malaria prevalence and population data as an example, the communities change, highlighting regions most strongly connected to areas of high burden. The approaches and results presented provide a flexible tool for supporting the design of disease surveillance and control strategies through mapping areas of high connectivity that form coherent units of intervention and key link routes between communities for targeting surveillance.",2018 Mar 16,"['Strano, Emanuele', 'Viana, Matheus P.', 'Sorichetta, Alessandro', 'Tatem, Andrew J.']",Sci Rep,,,True
dc3df0a30a76ca925a5cc4466528ea0c4dab9638,PMC,Bat-mouse bone marrow chimera: a novel animal model for dissecting the uniqueness of the bat immune system,http://dx.doi.org/10.1038/s41598-018-22899-1,PMC5856848,29549333,CC BY,"Bats are an important animal model with long lifespans, low incidences of tumorigenesis and an ability to asymptomatically harbour pathogens. Currently, in vivo studies of bats are hampered due to their low reproduction rates. To overcome this, we transplanted bat cells from bone marrow (BM) and spleen into an immunodeficient mouse strain NOD-scid IL-2R(−/−) (NSG), and have successfully established stable, long-term reconstitution of bat immune cells in mice (bat-mice). Immune functionality of our bat-mouse model was demonstrated through generation of antigen-specific antibody response by bat cells following immunization. Post-engraftment of total bat BM cells and splenocytes, bat immune cells survived, expanded and repopulated the mouse without any observable clinical abnormalities. Utilizing bat’s remarkable immunological functions, this novel model has a potential to be transformed into a powerful platform for basic and translational research.",2018 Mar 16,"['Yong, Kylie Su Mei', 'Ng, Justin Han Jia', 'Her, Zhisheng', 'Hey, Ying Ying', 'Tan, Sue Yee', 'Tan, Wilson Wei Sheng', 'Irac, Sergio Erdal', 'Liu, Min', 'Chan, Xue Ying', 'Gunawan, Merry', 'Foo, Randy Jee Hiang', 'Low, Dolyce Hong Wen', 'Mendenhall, Ian Hewitt', 'Chionh, Yok Teng', 'Dutertre, Charles-Antoine', 'Chen, Qingfeng', 'Wang, Lin-Fa']",Sci Rep,,,True
7c348bc2c3b8600f6decd933c9896ab10ace25c7,PMC,Self-Swabbing for Virological Confirmation of Influenza-Like Illness Among an Internet-Based Cohort in the UK During the 2014-2015 Flu Season: Pilot Study,http://dx.doi.org/10.2196/jmir.9084,PMC5856931,29496658,CC BY,"BACKGROUND: Routine influenza surveillance, based on laboratory confirmation of viral infection, often fails to estimate the true burden of influenza-like illness (ILI) in the community because those with ILI often manage their own symptoms without visiting a health professional. Internet-based surveillance can complement this traditional surveillance by measuring symptoms and health behavior of a population with minimal time delay. Flusurvey, the UK’s largest crowd-sourced platform for surveillance of influenza, collects routine data on more than 6000 voluntary participants and offers real-time estimates of ILI circulation. However, one criticism of this method of surveillance is that it is only able to assess ILI, rather than virologically confirmed influenza. OBJECTIVE: We designed a pilot study to see if it was feasible to ask individuals from the Flusurvey platform to perform a self-swabbing task and to assess whether they were able to collect samples with a suitable viral content to detect an influenza virus in the laboratory. METHODS: Virological swabbing kits were sent to pilot study participants, who then monitored their ILI symptoms over the influenza season (2014-2015) through the Flusurvey platform. If they reported ILI, they were asked to undertake self-swabbing and return the swabs to a Public Health England laboratory for multiplex respiratory virus polymerase chain reaction testing. RESULTS: A total of 700 swab kits were distributed at the start of the study; from these, 66 participants met the definition for ILI and were asked to return samples. In all, 51 samples were received in the laboratory, 18 of which tested positive for a viral cause of ILI (35%). CONCLUSIONS: This demonstrated proof of concept that it is possible to apply self-swabbing for virological laboratory testing to an online cohort study. This pilot does not have significant numbers to validate whether Flusurvey surveillance accurately reflects influenza infection in the community, but highlights that the methodology is feasible. Self-swabbing could be expanded to larger online surveillance activities, such as during the initial stages of a pandemic, to understand community transmission or to better assess interseasonal activity.",2018 Mar 1,"['Wenham, Clare', 'Gray, Eleanor R', 'Keane, Candice E', 'Donati, Matthew', 'Paolotti, Daniela', 'Pebody, Richard', 'Fragaszy, Ellen', 'McKendry, Rachel A', 'Edmunds, W John']",J Med Internet Res,,,False
43d9f57350fa37d6e0197483e3458ec01930db4e,PMC,Self-Swabbing for Virological Confirmation of Influenza-Like Illness Among an Internet-Based Cohort in the UK During the 2014-2015 Flu Season: Pilot Study,http://dx.doi.org/10.2196/jmir.9084,PMC5856931,29496658,CC BY,"BACKGROUND: Routine influenza surveillance, based on laboratory confirmation of viral infection, often fails to estimate the true burden of influenza-like illness (ILI) in the community because those with ILI often manage their own symptoms without visiting a health professional. Internet-based surveillance can complement this traditional surveillance by measuring symptoms and health behavior of a population with minimal time delay. Flusurvey, the UK’s largest crowd-sourced platform for surveillance of influenza, collects routine data on more than 6000 voluntary participants and offers real-time estimates of ILI circulation. However, one criticism of this method of surveillance is that it is only able to assess ILI, rather than virologically confirmed influenza. OBJECTIVE: We designed a pilot study to see if it was feasible to ask individuals from the Flusurvey platform to perform a self-swabbing task and to assess whether they were able to collect samples with a suitable viral content to detect an influenza virus in the laboratory. METHODS: Virological swabbing kits were sent to pilot study participants, who then monitored their ILI symptoms over the influenza season (2014-2015) through the Flusurvey platform. If they reported ILI, they were asked to undertake self-swabbing and return the swabs to a Public Health England laboratory for multiplex respiratory virus polymerase chain reaction testing. RESULTS: A total of 700 swab kits were distributed at the start of the study; from these, 66 participants met the definition for ILI and were asked to return samples. In all, 51 samples were received in the laboratory, 18 of which tested positive for a viral cause of ILI (35%). CONCLUSIONS: This demonstrated proof of concept that it is possible to apply self-swabbing for virological laboratory testing to an online cohort study. This pilot does not have significant numbers to validate whether Flusurvey surveillance accurately reflects influenza infection in the community, but highlights that the methodology is feasible. Self-swabbing could be expanded to larger online surveillance activities, such as during the initial stages of a pandemic, to understand community transmission or to better assess interseasonal activity.",2018 Mar 1,"['Wenham, Clare', 'Gray, Eleanor R', 'Keane, Candice E', 'Donati, Matthew', 'Paolotti, Daniela', 'Pebody, Richard', 'Fragaszy, Ellen', 'McKendry, Rachel A', 'Edmunds, W John']",J Med Internet Res,,,False
a042c56b2ccb9bbf4a77960590ccd33033abfe20,PMC,Self-Swabbing for Virological Confirmation of Influenza-Like Illness Among an Internet-Based Cohort in the UK During the 2014-2015 Flu Season: Pilot Study,http://dx.doi.org/10.2196/jmir.9084,PMC5856931,29496658,CC BY,"BACKGROUND: Routine influenza surveillance, based on laboratory confirmation of viral infection, often fails to estimate the true burden of influenza-like illness (ILI) in the community because those with ILI often manage their own symptoms without visiting a health professional. Internet-based surveillance can complement this traditional surveillance by measuring symptoms and health behavior of a population with minimal time delay. Flusurvey, the UK’s largest crowd-sourced platform for surveillance of influenza, collects routine data on more than 6000 voluntary participants and offers real-time estimates of ILI circulation. However, one criticism of this method of surveillance is that it is only able to assess ILI, rather than virologically confirmed influenza. OBJECTIVE: We designed a pilot study to see if it was feasible to ask individuals from the Flusurvey platform to perform a self-swabbing task and to assess whether they were able to collect samples with a suitable viral content to detect an influenza virus in the laboratory. METHODS: Virological swabbing kits were sent to pilot study participants, who then monitored their ILI symptoms over the influenza season (2014-2015) through the Flusurvey platform. If they reported ILI, they were asked to undertake self-swabbing and return the swabs to a Public Health England laboratory for multiplex respiratory virus polymerase chain reaction testing. RESULTS: A total of 700 swab kits were distributed at the start of the study; from these, 66 participants met the definition for ILI and were asked to return samples. In all, 51 samples were received in the laboratory, 18 of which tested positive for a viral cause of ILI (35%). CONCLUSIONS: This demonstrated proof of concept that it is possible to apply self-swabbing for virological laboratory testing to an online cohort study. This pilot does not have significant numbers to validate whether Flusurvey surveillance accurately reflects influenza infection in the community, but highlights that the methodology is feasible. Self-swabbing could be expanded to larger online surveillance activities, such as during the initial stages of a pandemic, to understand community transmission or to better assess interseasonal activity.",2018 Mar 1,"['Wenham, Clare', 'Gray, Eleanor R', 'Keane, Candice E', 'Donati, Matthew', 'Paolotti, Daniela', 'Pebody, Richard', 'Fragaszy, Ellen', 'McKendry, Rachel A', 'Edmunds, W John']",J Med Internet Res,,,False
629ac592d318e35f264604db7efe223965b3e509,PMC,Self-Swabbing for Virological Confirmation of Influenza-Like Illness Among an Internet-Based Cohort in the UK During the 2014-2015 Flu Season: Pilot Study,http://dx.doi.org/10.2196/jmir.9084,PMC5856931,29496658,CC BY,"BACKGROUND: Routine influenza surveillance, based on laboratory confirmation of viral infection, often fails to estimate the true burden of influenza-like illness (ILI) in the community because those with ILI often manage their own symptoms without visiting a health professional. Internet-based surveillance can complement this traditional surveillance by measuring symptoms and health behavior of a population with minimal time delay. Flusurvey, the UK’s largest crowd-sourced platform for surveillance of influenza, collects routine data on more than 6000 voluntary participants and offers real-time estimates of ILI circulation. However, one criticism of this method of surveillance is that it is only able to assess ILI, rather than virologically confirmed influenza. OBJECTIVE: We designed a pilot study to see if it was feasible to ask individuals from the Flusurvey platform to perform a self-swabbing task and to assess whether they were able to collect samples with a suitable viral content to detect an influenza virus in the laboratory. METHODS: Virological swabbing kits were sent to pilot study participants, who then monitored their ILI symptoms over the influenza season (2014-2015) through the Flusurvey platform. If they reported ILI, they were asked to undertake self-swabbing and return the swabs to a Public Health England laboratory for multiplex respiratory virus polymerase chain reaction testing. RESULTS: A total of 700 swab kits were distributed at the start of the study; from these, 66 participants met the definition for ILI and were asked to return samples. In all, 51 samples were received in the laboratory, 18 of which tested positive for a viral cause of ILI (35%). CONCLUSIONS: This demonstrated proof of concept that it is possible to apply self-swabbing for virological laboratory testing to an online cohort study. This pilot does not have significant numbers to validate whether Flusurvey surveillance accurately reflects influenza infection in the community, but highlights that the methodology is feasible. Self-swabbing could be expanded to larger online surveillance activities, such as during the initial stages of a pandemic, to understand community transmission or to better assess interseasonal activity.",2018 Mar 1,"['Wenham, Clare', 'Gray, Eleanor R', 'Keane, Candice E', 'Donati, Matthew', 'Paolotti, Daniela', 'Pebody, Richard', 'Fragaszy, Ellen', 'McKendry, Rachel A', 'Edmunds, W John']",J Med Internet Res,,,False
131e5a7c8626d4fec5bfe8d77666d1d8556e5a4c,PMC,Taraxacum officinale and Urtica dioica extracts inhibit dengue virus serotype 2 replication in vitro,http://dx.doi.org/10.1186/s12906-018-2163-3,PMC5857124,29548293,CC BY,"BACKGROUND: Urtica dioica, Taraxacum officinale, Calea integrifolia and Caesalpinia pulcherrima are widely used all over the world for treatment of different illnesses. In Mexico, these plants are traditionally used to alleviate or counteract rheumatism and inflammatory muscle diseases. In the present study we evaluated the activity of aqueous and methanolic extracts of these four plants, on the replication of dengue virus serotype 2 (DENV2). METHODS: Extraction process was carried out in a Soxtherm® system at 60, 85 and 120 °C; a chemical fractionation in silica gel chromatography was performed and compounds present in the active fractions were identified by HPLC-DAD-ESI/MSn. The cytotoxic concentration and the inhibitory effect of extracts or fractions on the DENV2 replication were analyzed in the BHK-21 cell line (plaque forming assay). The half maximal inhibitory concentration (IC(50)) and the selectivity index (SI) were calculated for the extracts and fractions. RESULTS: The methanolic extracts at 60 °C of T. officinale and U. dioica showed the higher inhibitory effects on DENV2 replication. After the chemical fractionation, the higher activity fraction was found for U. dioica and T. officinale, presenting IC(50) values of 165.7 ± 3.85 and 126.1 ± 2.80 μg/ml, respectively; SI values were 5.59 and 6.01 for each fraction. The compounds present in T. officinale, were luteolin and caffeoylquinic acids derivatives and quercertin diclycosides. The compounds in the active fraction of U. dioica, were, chlorogenic acid, quercertin derivatives and flavonol glycosides (quercetin and kaempferol). CONCLUSIONS: Two fractions from U. dioica and T. officinale methanolic extracts with anti-dengue activity were found. The compounds present in both fractions were identified, several recognized molecules have demonstrated activity against other viral species. Subsequent biological analysis of the molecules, alone or in combination, contained in the extracts will be carried out to develop therapeutics against DENV2.",2018 Mar 16,"['Flores-Ocelotl, María R.', 'Rosas-Murrieta, Nora H.', 'Moreno, Diego A.', 'Vallejo-Ruiz, Verónica', 'Reyes-Leyva, Julio', 'Domínguez, Fabiola', 'Santos-López, Gerardo']",BMC Complement Altern Med,,,True
ef6638accc1ef599ad1aafd47b3a86f2b904cc76,PMC,"Acute Hemorrhagic Encephalitis Responding to Combined Decompressive Craniectomy, Intravenous Immunoglobulin, and Corticosteroid Therapies: Association with Novel RANBP2 Variant",http://dx.doi.org/10.3389/fneur.2018.00130,PMC5857578,29593631,CC BY,"BACKGROUND: Acute hemorrhagic encephalomyelitis (AHEM) is considered as a rare form of acute disseminated encephalomyelitis characterized by fulminant encephalopathy with hemorrhagic necrosis and most often fatal outcome. OBJECTIVE: To report the association with Ran Binding Protein (RANBP2) gene variant and the response to decompressive craniectomy and high-dose intravenous methylprednisolone (IVMP) in life-threatening AHEM. DESIGN: Single case study. CASE REPORT: A 6-year-old girl known to have sickle cell disease (SCD) presented an acquired demyelinating syndrome (ADS) with diplopia due to sudden unilateral fourth nerve palsy. She received five pulses of IVMP (30 mg/kg/day). Two weeks after steroid weaning, she developed right hemiplegia and coma. Brain magnetic resonance imaging showed a left frontal necrotico-hemorrhagic lesion and new multifocal areas of demyelination. She underwent decompressive craniotomy and evacuation of an ongoing left frontoparietal hemorrhage. Comprehensive investigations ruled out vascular and infectious process. The neurological deterioration stopped concomitantly with combined neurosurgical drainage of the hematoma, decompressive craniotomy, IVMP, and intravenous immunoglobulins (IVIG). She developed during the following months Crohn disease and sclerosing cholangitis. After 2-year follow-up, there was no new neurological manifestation. The patient still suffered right hemiplegia and aphasia, but was able to walk. Cognitive/behavioral abilities significantly recovered. A heterozygous novel rare missense variant (c.4993A>G, p.Lys1665Glu) was identified in RANBP2, a gene associated with acute necrotizing encephalopathy. RANBP2 is a protein playing an important role in the energy homeostasis of neuronal cells. CONCLUSION: In any ADS occurring in the context of SCD and/or autoimmune condition, we recommend to slowly wean steroids and to closely monitor the patient after weaning to quickly treat any recurrence of neurological symptom with IVMP. This case report, in addition to others, stresses the likely efficacy of combined craniotomy, IVIG, and IVMP treatments in AHEM. RANBP2 mutations may sensitize the brain to inflammation and predispose to AHEM.",2018 Mar 12,"['Alawadhi, Abdulla', 'Saint-Martin, Christine', 'Bhanji, Farhan', 'Srour, Myriam', 'Atkinson, Jeffrey', 'Sébire, Guillaume']",Front Neurol,,,True
2c798963aaa2245c095624af78d5638bebf60c2f,PMC,Near-Patient Sampling to Assist Infection Control—A Case Report and Discussion,http://dx.doi.org/10.3390/ijerph15020238,PMC5858307,29385031,CC BY,"Air sampling as an aid to infection control is still in an experimental stage, as there is no consensus about which air samplers and pathogen detection methods should be used, and what thresholds of specific pathogens in specific exposed populations (staff, patients, or visitors) constitutes a true clinical risk. This case report used a button sampler, worn or held by staff or left free-standing in a fixed location, for environmental sampling around a child who was chronically infected by a respiratory adenovirus, to determine whether there was any risk of secondary adenovirus infection to the staff managing the patient. Despite multiple air samples taken on difference days, coinciding with high levels of adenovirus detectable in the child’s nasopharyngeal aspirates (NPAs), none of the air samples contained any detectable adenovirus DNA using a clinically validated diagnostic polymerase chain reaction (PCR) assay. Although highly sensitive, in-house PCR assays have been developed to detect airborne pathogen RNA/DNA, it is still unclear what level of specific pathogen RNA/DNA constitutes a true clinical risk. In this case, the absence of detectable airborne adenovirus DNA using a conventional diagnostic assay removed the requirement for staff to wear surgical masks and face visors when they entered the child’s room. No subsequent staff infections or outbreaks of adenovirus have so far been identified.",2018 Feb 31,"['Tang, Julian W.', 'Hoyle, Elizabeth', 'Moran, Sammy', 'Pareek, Manish']",Int J Environ Res Public Health,,,True
6ae480b7554d3210fa26f2410a6ed06ade025eec,PMC,Experimental infection of Cynomolgus Macaques with highly pathogenic H5N1 influenza virus through the aerosol route,http://dx.doi.org/10.1038/s41598-018-23022-0,PMC5859186,29556081,CC BY,"Several animal models are used to study influenza viruses. Intranasal inoculation of animals with a liquid inoculum is one of the main methods used to experimentally infect animals with influenza virus; however, this method does not reflect the natural infection with influenza virus by contact or aerosol route. Aerosol inhalation methods have been established with several influenza viruses for mouse and ferret models, but few studies have evaluated inoculation routes in a nonhuman primates (NHP) model. Here, we performed the experimental infection of NHPs with a highly pathogenic H5N1 influenza virus via the aerosol route and demonstrated that aerosol infection had no effect on clinical outcome, but caused broader infection throughout all of the lobes of the lung compared with a non-aerosolized approach. Aerosol infection therefore represents an option for inoculation of NHPs in future studies.",2018 Mar 19,"['Watanabe, Tokiko', 'Iwatsuki-Horimoto, Kiyoko', 'Kiso, Maki', 'Nakajima, Noriko', 'Takahashi, Kenta', 'Jose da Silva Lopes, Tiago', 'Ito, Mutsumi', 'Fukuyama, Satoshi', 'Hasegawa, Hideki', 'Kawaoka, Yoshihiro']",Sci Rep,,,True
e3f7e8c04762fc684f7ebfda560df8492e29929a,PMC,Epidemiological study of hemotropic mycoplasmas (hemoplasmas) in cats from central Spain,http://dx.doi.org/10.1186/s13071-018-2740-9,PMC5859754,29554981,CC BY,"BACKGROUND: Hemotropic mycoplasmas (hemoplasmas) have been found infecting cats worldwide. However, studies about feline hemoplasma infections in Spain are scarce. Therefore, the purpose of the research was to evaluate the prevalence of feline hemotropic mycoplasmas and to characterize risk factors and clinical findings associated with these infections in a cat population from the Madrid area, Spain. METHODS: Polymerase chain reaction (PCR) was employed to detect Mycoplasma haemofelis (Mhf), “Candidatus Mycoplasma haemominutum” (CMhm) and “Candidatus Mycoplasma turicensis” (CMt) in blood samples from 456 client-owned and 138 stray cats from Madrid. In order to assess associations between these hemoplasma infections and epidemiological parameters, data regarding signalment, environment, prophylaxis measures, retrovirus status, clinical signs and laboratory findings were compiled, whenever possible. RESULTS: DNA of feline hemoplasmas was detected from the blood of 63 out of 594 cats (10.6%), with a prevalence of 3.7% (22/594) for Mhf, 8.1% (48/594) for CMhm and 0.5% (3/594) for CMt. Stray cats had statistically higher prevalences of feline hemoplasmas (15.9%) and, specifically, of Mhf (8.7%) than client-owned cats (9 and 2.2%, respectively). A total of seven cats (1.17%) were co-infected with “Candidatus M. haemominutum” and M. haemofelis, two (0.33%) with “Candidatus M. haemominutum” and “Candidatus M. turicensis” and another one (0.17%) with M. haemofelis and Candidatus “M. turicensis”. Male gender, collection of blood during warm months and FeLV/FIV positivity status were associated with hemotropic mycoplasma infection in cats from Madrid. Additionally, within the group of client-owned cats, hemoplasma infection was associated with adult age, outdoor access, and the existence of low haematocrit, erythrocyte count and haemoglobin concentration values. CONCLUSIONS: To our knowledge, this is the first epidemiological survey of feline hemoplasmas performed in central Spain (Madrid). Our study confirms that “Ca. Mycoplasma haemominutum”, Mycoplasma haemofelis and “Ca. Mycoplasma turicensis” are infecting client-owned and stray cats in this region of Spain, “Ca. Mycoplasma haemominutum” being the most prevalent species. More studies are necessary to help understand the role of the natural infection by these species of hemoplasma in cats.",2018 Mar 20,"['Díaz-Regañón, David', 'Villaescusa, Alejandra', 'Ayllón, Tania', 'Rodríguez-Franco, Fernando', 'García-Sancho, Mercedes', 'Agulla, Beatriz', 'Sainz, Ángel']",Parasit Vectors,,,True
43f0fd3b0c765c0dc92a49d8ac4a50a75a0135b7,PMC,"Dengue viruses cleave STING in humans but not in nonhuman primates, their presumed natural reservoir",http://dx.doi.org/10.7554/eLife.31919,PMC5860865,29557779,CC BY,"Human dengue viruses emerged from primate reservoirs, yet paradoxically dengue does not reach high titers in primate models. This presents a unique opportunity to examine the genetics of spillover versus reservoir hosts. The dengue virus 2 (DENV2) - encoded protease cleaves human STING, reducing type I interferon production and boosting viral titers in humans. We find that both human and sylvatic (reservoir) dengue viruses universally cleave human STING, but not the STING of primates implicated as reservoir species. The special ability of dengue to cleave STING is thus specific to humans and a few closely related ape species. Conversion of residues 78/79 to the human-encoded ‘RG’ renders all primate (and mouse) STINGs sensitive to viral cleavage. Dengue viruses may have evolved to increase viral titers in the dense and vast human population, while maintaining decreased titers and pathogenicity in the more rare animals that serve as their sustaining reservoir in nature.",,"['Stabell, Alex C', 'Meyerson, Nicholas R', 'Gullberg, Rebekah C', 'Gilchrist, Alison R', 'Webb, Kristofor J', 'Old, William M', 'Perera, Rushika', 'Sawyer, Sara L']",eLife.; 7:e31919,,,True
a47e8b0ef5e149093968348821c1dec778685e23,PMC,"Dengue viruses cleave STING in humans but not in nonhuman primates, their presumed natural reservoir",http://dx.doi.org/10.7554/eLife.31919,PMC5860865,29557779,CC BY,"Human dengue viruses emerged from primate reservoirs, yet paradoxically dengue does not reach high titers in primate models. This presents a unique opportunity to examine the genetics of spillover versus reservoir hosts. The dengue virus 2 (DENV2) - encoded protease cleaves human STING, reducing type I interferon production and boosting viral titers in humans. We find that both human and sylvatic (reservoir) dengue viruses universally cleave human STING, but not the STING of primates implicated as reservoir species. The special ability of dengue to cleave STING is thus specific to humans and a few closely related ape species. Conversion of residues 78/79 to the human-encoded ‘RG’ renders all primate (and mouse) STINGs sensitive to viral cleavage. Dengue viruses may have evolved to increase viral titers in the dense and vast human population, while maintaining decreased titers and pathogenicity in the more rare animals that serve as their sustaining reservoir in nature.",,"['Stabell, Alex C', 'Meyerson, Nicholas R', 'Gullberg, Rebekah C', 'Gilchrist, Alison R', 'Webb, Kristofor J', 'Old, William M', 'Perera, Rushika', 'Sawyer, Sara L']",eLife.; 7:e31919,,,False
c26196c940aab1a9c43e70d5428672644d1e0972,PMC,"Abstracts from the 25th European Society for Animal Cell Technology Meeting: Cell Technologies for Innovative Therapies: Lausanne, Switzerland. 14-17 May 2017",http://dx.doi.org/10.1186/s12919-018-0097-x,PMC5861492,,CC BY,,2018 Mar 15,,BMC Proc,,,True
525511c3e146527c02bc25aed2833f0ef103d62a,PMC,IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes,http://dx.doi.org/10.1186/s12890-018-0616-6,PMC5861655,29562888,CC BY,"BACKGROUND: Interferon lambdas (IFNLs) have important anti-viral/bacterial and immunomodulatory functions in the respiratory tract. How do IFNLs impact COPD and its exacerbations? METHODS: Five hundred twenty eight patients were recruited in a prospective observational multicentre cohort (PROMISE) study. The genetic polymorphisms (rs8099917 and rs12979860) within the IFNL3/4 gene region and circulating levels of IFNL3 in COPD patients were determined and associated with disease activity and outcome during a median follow-up of 24 months. RESULTS: The GG genotype significantly influenced severe exacerbation rate (42 vs. 23%; p = 0.032) and time to severe exacerbation (HR = 2.260; p = 0.012). Compared to the TT or TG genotypes, the GG genotype was associated with severe dyspnoea (modified medical research council score ≥ median 3; 22 vs 42%, p = 0.030). The CC genotype of the rs12979860 SNP was associated with a poorer prognosis (body mass index, airflow obstruction, dyspnea and exercise capacity index ≥ median 4; 46 vs. 36% TC vs. 20.5% TT; p = 0.031). Patients with stable COPD and at exacerbation had significantly lower circulating IFNL3 compared to healthy controls (p < 0.001 and p < 0.001, respectively). Circulating IFNL3 correlated to post-bronchodilator FEV(1)%predicted and the tissue maturation biomarker Pro-collagen 3. CONCLUSION: IFNL3/4 polymorphisms and circulating IFNL3 may be associated with disease activity and outcomes in COPD. TRIAL REGISTRATION: Clinical Trial registration http://www.isrctn.com/ identifier ISRCTN99586989 on 16 April 2008.",2018 Mar 21,"['Egli, Adrian', 'Mandal, Jyotshna', 'Schumann, Desiree M.', 'Roth, Michael', 'Thomas, Brad', 'Lorne Tyrrell, D.', 'Blasi, Francesco', 'Kostikas, Kostantinos', 'Boersma, Wim', 'Milenkovic, Branislava', 'Lacoma, Alicia', 'Rentsch, Katharina', 'Rohde, Gernot G. U.', 'Louis, Renaud', 'Aerts, Joachim G.', 'Welte, Tobias', 'Torres, Antoni', 'Tamm, Michael', 'Stolz, Daiana']",BMC Pulm Med,,,True
c825a4d277f3300983a01b6961865b8377e87cf0,PMC,Immunobiotics for the Bovine Host: Their Interaction with Intestinal Epithelial Cells and Their Effect on Antiviral Immunity,http://dx.doi.org/10.3389/fimmu.2018.00326,PMC5863502,29599767,CC BY,"The scientific community has reported several cases of microbes that exhibit elevated rates of antibiotic resistance in different regions of the planet. Due to this emergence of antimicrobial resistant microorganisms, the use of antibiotics as promoters of livestock animals’ growth is being banned in most countries around the world. One of the challenges of agricultural immunology therefore is to find alternatives by modulating the immune system of animals in drug-independent safe food production systems. In this regard, in an effort to supplant antibiotics from bovine feeds, several alternatives were proposed including the use of immunomodulatory probiotics (immunobiotics). The purpose of this review is to provide an update of the status of the modulation of intestinal antiviral innate immunity of the bovine host by immunobiotics, and the beneficial impact of immunobiotics on viral infections, focused on intestinal epithelial cells (IECs). The results of our group, which demonstrate the capacity of immunobiotic strains to beneficially modulate Toll-like receptor 3-triggered immune responses in bovine IECs and improve the resistance to viral infections, are highlighted. This review provides comprehensive information on the innate immune response of bovine IECs against virus, which can be further investigated for the development of strategies aimed to improve defenses in the bovine host.",2018 Mar 2,"['Villena, Julio', 'Aso, Hisashi', 'Rutten, Victor P. M. G.', 'Takahashi, Hideki', 'van Eden, Willem', 'Kitazawa, Haruki']",Front Immunol,,,True
b7e0f3776f44e29508da3d6150d63790e7f38d9e,PMC,MERS-CoV pathogenesis and antiviral efficacy of licensed drugs in human monocyte-derived antigen-presenting cells,http://dx.doi.org/10.1371/journal.pone.0194868,PMC5864050,29566060,CC0,"Middle East respiratory syndrome coronavirus (MERS-CoV) presents an emerging threat to public health worldwide by causing severe respiratory disease in humans with high virulence and case fatality rate (about 35%) since 2012. Little is known about the pathogenesis and innate antiviral response in primary human monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs) upon MERS-CoV infection. In this study, we assessed MERS-CoV replication as well as induction of inflammatory cytokines and chemokines in MDMs and immature and mature MDDCs. Immature MDDCs and MDMs were permissive for MERS-CoV infection, while mature MDDCs were not, with stimulation of proinflammatory cytokine and chemokine upregulation in MDMs, but not in MDDCs. To further evaluate the antiviral activity of well-defined drugs in primary antigen presenting cells (APCs), three compounds (chloroquine, chlorpromazine and toremifine), each with broad-spectrum antiviral activity in immortalized cell lines, were evaluated in MDMs and MDDCs to determine their antiviral effect on MERS-CoV infection. While chloroquine was not active in these primary cells, chlorpromazine showed strong anti-MERS-CoV activity, but it was associated with high cytotoxicity narrowing the potential window for drug utilization. Unlike in established cells, toremifene had marginal activity when tested in antigen presenting cells, with high apparent cytotoxicity, also limiting its potential as a therapeutic option. These results demonstrate the value of testing drugs in primary cells, in addition to established cell lines, before initiating preclinical or clinical studies for MERS treatment and the importance of carefully assessing cytotoxicity in drug screen assays. Furthermore, these studies also highlight the role of APCs in stimulating a robust protective immune response to MERS-CoV infection.",2018 Mar 22,"['Cong, Yu', 'Hart, Brit J.', 'Gross, Robin', 'Zhou, Huanying', 'Frieman, Matthew', 'Bollinger, Laura', 'Wada, Jiro', 'Hensley, Lisa E.', 'Jahrling, Peter B.', 'Dyall, Julie', 'Holbrook, Michael R.']",PLoS One,,,True
30f8d46cca4f068ecc358d99115a885d458ad9b7,PMC,Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs,http://dx.doi.org/10.1371/journal.pone.0194880,PMC5864066,29566079,CC0,"Identifying effective antivirals for treating Ebola virus disease (EVD) and minimizing transmission of such disease is critical. A variety of cell-based assays have been developed for evaluating compounds for activity against Ebola virus. However, very few reports discuss the variable assay conditions that can affect the results obtained from these drug screens. Here, we describe variable conditions tested during the development of our cell-based drug screen assays designed to identify compounds with anti-Ebola virus activity using established cell lines and human primary cells. The effect of multiple assay readouts and variable assay conditions, including virus input, time of infection, and the cell passage number, were compared, and the impact on the effective concentration for 50% and/ or 90% inhibition (EC(50), EC(90)) was evaluated using the FDA-approved compound, toremifene citrate. In these studies, we show that altering cell-based assay conditions can have an impact on apparent drug potency as measured by the EC(50). These results further support the importance of developing standard operating procedures for generating reliable and reproducible in vitro data sets for potential antivirals.",2018 Mar 22,"['Postnikova, Elena', 'Cong, Yu', 'DeWald, Lisa Evans', 'Dyall, Julie', 'Yu, Shuiqing', 'Hart, Brit J.', 'Zhou, Huanying', 'Gross, Robin', 'Logue, James', 'Cai, Yingyun', 'Deiuliis, Nicole', 'Michelotti, Julia', 'Honko, Anna N.', 'Bennett, Richard S.', 'Holbrook, Michael R.', 'Olinger, Gene G.', 'Hensley, Lisa E.', 'Jahrling, Peter B.']",PLoS One,,,True
09e56ff472829444bd7a1670f61fb696fac7ba2c,PMC,Macrodomain ADP-ribosylhydrolase and the pathogenesis of infectious diseases,http://dx.doi.org/10.1371/journal.ppat.1006864,PMC5864081,29566066,CC BY,,2018 Mar 22,"['Leung, Anthony K. L.', 'McPherson, Robert Lyle', 'Griffin, Diane E.']",PLoS Pathog,,,True
ea12b82b2723bb4b1257bc8d4d2e61c39b27ba41,PMC,Molecular basis of binding between the global post-transcriptional regulator CsrA and the T3SS chaperone CesT,http://dx.doi.org/10.1038/s41467-018-03625-x,PMC5864733,29567971,CC BY,"The T3SS chaperone CesT is recently shown to interact with the post-transcriptional regulator CsrA to modulate post-attachment signaling in enteropathogenic and enterohemorrhagic Escherichia coli. The molecular basis of the CesT/CsrA binding, however, remains elusive. Here, we show that CesT and CsrA both created two ligand binding sites in their homodimers, forming irregular multimeric complexes in solution. Through construction of a recombinant CsrA-dimer (Re-CsrA) that contains a single CesT binding site, the atomic binding features between CesT and CsrA are delineated via the structure of the CesT/Re-CsrA complex. In contrast to a previously reported N-terminally swapped dimer-form, CesT adopts a dimeric architecture with a swapped C-terminal helix for CsrA engagement. In CsrA, CesT binds to a surface patch that extensively overlaps with its mRNA binding site. The binding mode therefore justifies a mechanism of CsrA-modulation by CesT via competitive inhibition of the CsrA/mRNA interactions.",2018 Mar 22,"['Ye, Fei', 'Yang, Fanli', 'Yu, Ruijie', 'Lin, Xi', 'Qi, Jianxun', 'Chen, Zhujun', 'Cao, Yu', 'Wei, Yuquan', 'Gao, George F.', 'Lu, Guangwen']",Nat Commun,,,False
7f011d5856d476496de3e715d8f77908f2610e30,PMC,Molecular basis of binding between the global post-transcriptional regulator CsrA and the T3SS chaperone CesT,http://dx.doi.org/10.1038/s41467-018-03625-x,PMC5864733,29567971,CC BY,"The T3SS chaperone CesT is recently shown to interact with the post-transcriptional regulator CsrA to modulate post-attachment signaling in enteropathogenic and enterohemorrhagic Escherichia coli. The molecular basis of the CesT/CsrA binding, however, remains elusive. Here, we show that CesT and CsrA both created two ligand binding sites in their homodimers, forming irregular multimeric complexes in solution. Through construction of a recombinant CsrA-dimer (Re-CsrA) that contains a single CesT binding site, the atomic binding features between CesT and CsrA are delineated via the structure of the CesT/Re-CsrA complex. In contrast to a previously reported N-terminally swapped dimer-form, CesT adopts a dimeric architecture with a swapped C-terminal helix for CsrA engagement. In CsrA, CesT binds to a surface patch that extensively overlaps with its mRNA binding site. The binding mode therefore justifies a mechanism of CsrA-modulation by CesT via competitive inhibition of the CsrA/mRNA interactions.",2018 Mar 22,"['Ye, Fei', 'Yang, Fanli', 'Yu, Ruijie', 'Lin, Xi', 'Qi, Jianxun', 'Chen, Zhujun', 'Cao, Yu', 'Wei, Yuquan', 'Gao, George F.', 'Lu, Guangwen']",Nat Commun,,,True
37a7937db6ae6abd28ead7c4956ae68850faa8ce,PMC,"Complete Genome Sequence of Human Coronavirus NL63 CN0601/14, First Isolated in South Korea",http://dx.doi.org/10.1128/genomeA.00152-18,PMC5864941,29567734,CC BY,"We report here the complete genome sequence of the human coronavirus NL63 CN0601/14 strain, first isolated from South Korea. It contains 18-nucleotide discontinuous deletions of the open reading frame 1a (ORF1a) and spike regions. This study will aid in our understanding of the complete genome sequences of isolated coronaviruses in South Korea.",2018 Mar 22,"['Kim, Jeong-Min', 'Kim, Seung-Tae', 'Yang, Jeong-Sun', 'Kim, Sung Soon', 'Cheong, Hyang-Min']",Genome Announc,,,True
7a488aaf9773826634d7018c0da282421523ba6c,PMC,A pilot study on primary cultures of human respiratory tract epithelial cells to predict patients’ responses to H7N9 infection,http://dx.doi.org/10.18632/oncotarget.24537,PMC5865685,29581859,CC BY,"Avian influenza A(H7N9) virus infections frequently lead to acute respiratory distress syndrome and death in humans. We aimed to investigate whether primary cultures of human respiratory tract epithelial cells are helpful to understand H7N9 virus pathogenesis and tissue tropism, and to evaluate how patient-related characteristics can affect the host's response to infection. Normal human bronchial epithelial cells (isolated from two different donors) and primary epithelial cells (harvested from 27 patients undergoing airway surgery) were experimentally infected with H7N9 and/or H1N1pdm for 72 h. After virus infection, the culture media were collected for viral RNA quantitation and cytokine detection. Both H7N9 and H1N1pdm viruses replicated and induced a cytokine response differently for each donor in the normal human bronchial epithelial model. H7N9 replicated equivalently in epithelial cells harvested from the inferior turbinate and paranasal sinus, and those from the larynx and bronchus, at 72 h post-infection. Viral RNA quantity at 72 h was significantly higher in patients aged 21–64 years than in patients aged ≥ 65 years; however, no effects of sex, medical comorbidities, and obesity were noted. H7N9-infected cultured cells released multiple cytokines within 72 h. Levels of interleukin-1β, interleukin-6, interleukin-8, interferon-γ, and tumor necrosis factor-α were associated differently with patient-related characteristics (such as age, sex, obesity, and medical comorbidities). In the era of precision medicine, these findings illustrate the potential utility of this primary culture approach to predict a host's response to H7N9 infection or to future infection by newly emerging viral infections, and to dissect viral pathogenesis.",2018 Feb 20,"['Huang, Chung-Guei', 'Lee, Li-Ang', 'Wu, Yi-Cheng', 'Hsiao, Mei-Jen', 'Horng, Jim-Tong', 'Kuo, Rei-Lin', 'Huang, Chih-Heng', 'Lin, Ya-Chu', 'Tsao, Kuo-Chien', 'Chen, Min-Chi', 'Chen, Tse-Ching', 'Shih, Shin-Ru']",Oncotarget,,,True
8780e9524d9271a7b8e789f0f8c4eb6860ca8c50,PMC,"Avian viral surveillance in Victoria, Australia, and detection of two novel avian herpesviruses",http://dx.doi.org/10.1371/journal.pone.0194457,PMC5865735,29570719,CC BY,"Viruses in avian hosts can pose threats to avian health and some have zoonotic potential. Hospitals that provide veterinary care for avian patients may serve as a site of exposure of other birds and human staff in the facility to these viruses. They can also provide a useful location to collect samples from avian patients in order to examine the viruses present in wild birds. This study aimed to investigate viruses of biosecurity and/or zoonotic significance in Australian birds by screening samples collected from 409 birds presented to the Australian Wildlife Health Centre at Zoos Victoria’s Healesville Sanctuary for veterinary care between December 2014 and December 2015. Samples were tested for avian influenza viruses, herpesviruses, paramyxoviruses and coronaviruses, using genus- or family-wide polymerase chain reaction methods coupled with sequencing and phylogenetic analyses for detection and identification of both known and novel viruses. A very low prevalence of viruses was detected. Columbid alphaherpesvirus 1 was detected from a powerful owl (Ninox strenua) with inclusion body hepatitis, and an avian paramyxovirus most similar to Avian avulavirus 5 was detected from a musk lorikeet (Glossopsitta concinna). Two distinct novel avian alphaherpesviruses were detected in samples from a sulphur-crested cockatoo (Cacatua galerita) and a tawny frogmouth (Podargus strigoides). Avian influenza viruses and avian coronaviruses were not detected. The clinical significance of the newly detected viruses remains undetermined. Further studies are needed to assess the host specificity, epidemiology, pathogenicity and host-pathogen relationships of these novel viruses. Further genome characterization is also indicated, and would be required before these viruses can be formally classified taxonomically. The detection of these viruses contributes to our knowledge on avian virodiversity. The low level of avian virus detection, and the absence of any viruses with zoonotic potential, suggests low risk to biosecurity and human health.",2018 Mar 23,"['Amery-Gale, Jemima', 'Hartley, Carol A.', 'Vaz, Paola K.', 'Marenda, Marc S.', 'Owens, Jane', 'Eden, Paul A.', 'Devlin, Joanne M.']",PLoS One,,,True
b6b083c197d1f01a9fe29b40ad10f893db7a263f,PMC,"Detection and Characterization of a Novel Norovirus in Bats, China",http://dx.doi.org/10.1007/s12250-018-0010-9,PMC5866260,29508188,CC BY,,2018 Mar 5,"['Yang, Ling’en', 'Wang, Quanxi', 'Xu, Lin', 'Tu, Changchun', 'Huang, Xiaohong', 'He, Biao']",Virol Sin,,,True
b5d836ef3f064ed0bf47d2fa690786815ad26659,PMC,Dynamics of Zika virus outbreaks: an overview of mathematical modeling approaches,http://dx.doi.org/10.7717/peerj.4526,PMC5866925,29593941,CC BY,"BACKGROUND: The Zika virus was first discovered in 1947. It was neglected until a major outbreak occurred on Yap Island, Micronesia, in 2007. Teratogenic effects resulting in microcephaly in newborn infants is the greatest public health threat. In 2016, the Zika virus epidemic was declared as a Public Health Emergency of International Concern (PHEIC). Consequently, mathematical models were constructed to explicitly elucidate related transmission dynamics. SURVEY METHODOLOGY: In this review article, two steps of journal article searching were performed. First, we attempted to identify mathematical models previously applied to the study of vector-borne diseases using the search terms “dynamics,” “mathematical model,” “modeling,” and “vector-borne” together with the names of vector-borne diseases including chikungunya, dengue, malaria, West Nile, and Zika. Then the identified types of model were further investigated. Second, we narrowed down our survey to focus on only Zika virus research. The terms we searched for were “compartmental,” “spatial,” “metapopulation,” “network,” “individual-based,” “agent-based” AND “Zika.” All relevant studies were included regardless of the year of publication. We have collected research articles that were published before August 2017 based on our search criteria. In this publication survey, we explored the Google Scholar and PubMed databases. RESULTS: We found five basic model architectures previously applied to vector-borne virus studies, particularly in Zika virus simulations. These include compartmental, spatial, metapopulation, network, and individual-based models. We found that Zika models carried out for early epidemics were mostly fit into compartmental structures and were less complicated compared to the more recent ones. Simple models are still commonly used for the timely assessment of epidemics. Nevertheless, due to the availability of large-scale real-world data and computational power, recently there has been growing interest in more complex modeling frameworks. DISCUSSION: Mathematical models are employed to explore and predict how an infectious disease spreads in the real world, evaluate the disease importation risk, and assess the effectiveness of intervention strategies. As the trends in modeling of infectious diseases have been shifting towards data-driven approaches, simple and complex models should be exploited differently. Simple models can be produced in a timely fashion to provide an estimation of the possible impacts. In contrast, complex models integrating real-world data require more time to develop but are far more realistic. The preparation of complicated modeling frameworks prior to the outbreaks is recommended, including the case of future Zika epidemic preparation.",2018 Mar 22,"['Wiratsudakul, Anuwat', 'Suparit, Parinya', 'Modchang, Charin']",PeerJ,,,True
9d08ea3b664cb3fce5ee8ff79426b5dc211352bb,PMC,Factors Informing Outcomes for Older Cats and Dogs in Animal Shelters,http://dx.doi.org/10.3390/ani8030036,PMC5867524,29518897,CC BY,"SIMPLE SUMMARY: Historically, older cats and dogs have been particularly at-risk for euthanasia in animal shelters due to their lower perceived appeal for adoption. This study found that the condition at intake had the greatest impact on the outcomes of older cats and dogs. Additionally, the application of specialized veterinary care, such as orthopedic surgery or chronic disease maintenance, is discussed as factors that inform higher rates of live outcomes for these senior companion animals. These findings demonstrate that if shelters integrate practices that address the specific needs of ageing companion animals, the live outcomes for this population can increase. ABSTRACT: With advances in veterinary medicine that can increase the lifespan of cats and dogs and the effectiveness of spay/neuter programs in reducing the juvenile population of pets, animal shelters are experiencing an increasing population of older companion animals in their care. The purpose of this study was to assess the factors that inform the outcomes of these older cats and dogs. The sample consisted of 124 cats and 122 dogs that were over the age of 84 months (seven years) who were taken into a shelter over a one-year period. To assess the impact of condition at intake on the outcome for the senior animals, a multinomial logistic regression was performed. These findings indicate that preventative programming that can address the reasons these older animals are surrendered, as well as advancements in specialized medical or behavioral programs for ageing companion animals, may support an increase in live outcomes for older cats and dogs in shelters. Further study is needed to evaluate how the quality of life of older animals is impacted by remaining in the care of shelters rather than being euthanized.",2018 Mar 7,"['Hawes, Sloane', 'Kerrigan, Josephine', 'Morris, Kevin']",Animals (Basel),,,True
feb72aaab347ff388a21fc4d96575c5cbf29c020,PMC,"Severe influenza A(H1N1)pdm09 in pregnant women and neonatal outcomes, State of Sao Paulo, Brazil, 2009",http://dx.doi.org/10.1371/journal.pone.0194392,PMC5868799,29579099,CC BY,"To investigate the factors associated with death and describe the gestational outcomes in pregnant women with influenza A(H1N1)pdm09, we conducted a case-control study (deaths and recovered) in hospitalized pregnant women with laboratory-confirmed influenza A(H1N1)pdm09 with severe acute respiratory illness (SARI) in the state of São Paulo from June 9 to December 1, 2009. All cases were evaluated, and four controls that were matched by the epidemiological week of hospitalization of the case were randomly selected for each case. Cases and controls were selected from the National Disease Notification System-SINAN Influenza-web. The hospital records from 126 hospitals were evaluated, and home interviews were conducted using standardized forms. A total of 48 cases and 185 controls were investigated. Having had a previous health visit to a healthcare provider for an influenza episode before hospital admission was a risk factor for death (adjusted OR (OR(adj)) of 7.93, 95% CI 2.19–28.69). Although not significant in the multiple analysis (OR(adj) of 2.13, 95% CI 0.91–5.00), the 3(rd) trimester deserves attention, with an OR = 2.22, 95% CI 1.13–4.37 in the univariate analysis. Antiviral treatment was a protective factor when administered within 48 hours of symptom onset (OR(adj) = 0.16, 95% CI 0.05–0.50) and from 48 to 72 hours (OR(adj) = 0.09, 95% CI 0.01–0.87). There was a higher proportion of fetal deaths and preterm births among cases (p = 0.001) and live births with low weight (p = 0.019), compared to control subjects who gave birth during hospitalization. After discharge, control subjects had a favorable neonatal outcome. Early antiviral treatment during the presence of a flu-like illness is an important factor in reducing mortality from influenza in pregnant women and unfavorable neonatal outcomes. It is important to monitor pregnant women, particularly in the 3(rd) trimester of gestation, with influenza illness for diagnosis and early treatment.",2018 Mar 26,"['Ribeiro, Ana Freitas', 'Pellini, Alessandra Cristina Guedes', 'Kitagawa, Beatriz Yuko', 'Marques, Daniel', 'Madalosso, Geraldine', 'Fred, Joao', 'Albernaz, Ricardo Kerti Mangabeira', 'Carvalhanas, Telma Regina Marques Pinto', 'Zanetta, Dirce Maria Trevisan']",PLoS One,,,True
2870d8384735793d033aac6c0621f35540b59736,PMC,A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa,http://dx.doi.org/10.1371/journal.pone.0194527,PMC5868816,29579103,CC0,"Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.",2018 Mar 26,"['Geldenhuys, Marike', 'Mortlock, Marinda', 'Weyer, Jacqueline', 'Bezuidt, Oliver', 'Seamark, Ernest C. J.', 'Kearney, Teresa', 'Gleasner, Cheryl', 'Erkkila, Tracy H.', 'Cui, Helen', 'Markotter, Wanda']",PLoS One,,,True
14532cef46d13a950cff87e32056d14e8fdb55b7,PMC,A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa,http://dx.doi.org/10.1371/journal.pone.0194527,PMC5868816,29579103,CC0,"Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.",2018 Mar 26,"['Geldenhuys, Marike', 'Mortlock, Marinda', 'Weyer, Jacqueline', 'Bezuidt, Oliver', 'Seamark, Ernest C. J.', 'Kearney, Teresa', 'Gleasner, Cheryl', 'Erkkila, Tracy H.', 'Cui, Helen', 'Markotter, Wanda']",PLoS One,,,False
7069d9757fb795a7f8d8a6ea1d8b2c366a5c2003,PMC,A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa,http://dx.doi.org/10.1371/journal.pone.0194527,PMC5868816,29579103,CC0,"Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.",2018 Mar 26,"['Geldenhuys, Marike', 'Mortlock, Marinda', 'Weyer, Jacqueline', 'Bezuidt, Oliver', 'Seamark, Ernest C. J.', 'Kearney, Teresa', 'Gleasner, Cheryl', 'Erkkila, Tracy H.', 'Cui, Helen', 'Markotter, Wanda']",PLoS One,,,False
dbeaf2e9c4464a6657a8e3b105f18ebbcf267f2f,PMC,A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa,http://dx.doi.org/10.1371/journal.pone.0194527,PMC5868816,29579103,CC0,"Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.",2018 Mar 26,"['Geldenhuys, Marike', 'Mortlock, Marinda', 'Weyer, Jacqueline', 'Bezuidt, Oliver', 'Seamark, Ernest C. J.', 'Kearney, Teresa', 'Gleasner, Cheryl', 'Erkkila, Tracy H.', 'Cui, Helen', 'Markotter, Wanda']",PLoS One,,,False
7d0bbf600379659022265698caf0000891dc1584,PMC,A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa,http://dx.doi.org/10.1371/journal.pone.0194527,PMC5868816,29579103,CC0,"Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.",2018 Mar 26,"['Geldenhuys, Marike', 'Mortlock, Marinda', 'Weyer, Jacqueline', 'Bezuidt, Oliver', 'Seamark, Ernest C. J.', 'Kearney, Teresa', 'Gleasner, Cheryl', 'Erkkila, Tracy H.', 'Cui, Helen', 'Markotter, Wanda']",PLoS One,,,False
ca5c8c2a2b0a3ff05d8a0275f0235f4df21ec60c,PMC,A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa,http://dx.doi.org/10.1371/journal.pone.0194527,PMC5868816,29579103,CC0,"Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.",2018 Mar 26,"['Geldenhuys, Marike', 'Mortlock, Marinda', 'Weyer, Jacqueline', 'Bezuidt, Oliver', 'Seamark, Ernest C. J.', 'Kearney, Teresa', 'Gleasner, Cheryl', 'Erkkila, Tracy H.', 'Cui, Helen', 'Markotter, Wanda']",PLoS One,,,False
449ca6fb44785a5622501e8534307c72c719b1c3,PMC,A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa,http://dx.doi.org/10.1371/journal.pone.0194527,PMC5868816,29579103,CC0,"Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.",2018 Mar 26,"['Geldenhuys, Marike', 'Mortlock, Marinda', 'Weyer, Jacqueline', 'Bezuidt, Oliver', 'Seamark, Ernest C. J.', 'Kearney, Teresa', 'Gleasner, Cheryl', 'Erkkila, Tracy H.', 'Cui, Helen', 'Markotter, Wanda']",PLoS One,,,False
38df79d66805216ebb15bed68583634611897d00,PMC,A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa,http://dx.doi.org/10.1371/journal.pone.0194527,PMC5868816,29579103,CC0,"Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.",2018 Mar 26,"['Geldenhuys, Marike', 'Mortlock, Marinda', 'Weyer, Jacqueline', 'Bezuidt, Oliver', 'Seamark, Ernest C. J.', 'Kearney, Teresa', 'Gleasner, Cheryl', 'Erkkila, Tracy H.', 'Cui, Helen', 'Markotter, Wanda']",PLoS One,,,False
cae20303747b2f1cd0bf5d956fcff10a3ff036b9,PMC,A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa,http://dx.doi.org/10.1371/journal.pone.0194527,PMC5868816,29579103,CC0,"Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.",2018 Mar 26,"['Geldenhuys, Marike', 'Mortlock, Marinda', 'Weyer, Jacqueline', 'Bezuidt, Oliver', 'Seamark, Ernest C. J.', 'Kearney, Teresa', 'Gleasner, Cheryl', 'Erkkila, Tracy H.', 'Cui, Helen', 'Markotter, Wanda']",PLoS One,,,False
c99a7c2db63af37c927264171544ba589994e763,PMC,A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa,http://dx.doi.org/10.1371/journal.pone.0194527,PMC5868816,29579103,CC0,"Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.",2018 Mar 26,"['Geldenhuys, Marike', 'Mortlock, Marinda', 'Weyer, Jacqueline', 'Bezuidt, Oliver', 'Seamark, Ernest C. J.', 'Kearney, Teresa', 'Gleasner, Cheryl', 'Erkkila, Tracy H.', 'Cui, Helen', 'Markotter, Wanda']",PLoS One,,,False
4e6e3ca97349df9c2856a63b74fa6dadadc4ff8f,PMC,A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa,http://dx.doi.org/10.1371/journal.pone.0194527,PMC5868816,29579103,CC0,"Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.",2018 Mar 26,"['Geldenhuys, Marike', 'Mortlock, Marinda', 'Weyer, Jacqueline', 'Bezuidt, Oliver', 'Seamark, Ernest C. J.', 'Kearney, Teresa', 'Gleasner, Cheryl', 'Erkkila, Tracy H.', 'Cui, Helen', 'Markotter, Wanda']",PLoS One,,,False
8ace20b674c2bc5f71e195f68c703f66efd97b8b,PMC,Host gene expression profiles in ferrets infected with genetically distinct henipavirus strains,http://dx.doi.org/10.1371/journal.pntd.0006343,PMC5868854,29538374,CC BY,"Henipavirus infection causes severe respiratory and neurological disease in humans that can be fatal. To characterize the pathogenic mechanisms of henipavirus infection in vivo, we performed experimental infections in ferrets followed by genome-wide gene expression analysis of lung and brain tissues. The Hendra, Nipah-Bangladesh, and Nipah-Malaysia strains caused severe respiratory and neurological disease with animals succumbing around 7 days post infection. Despite the presence of abundant viral shedding, animal-to-animal transmission did not occur. The host gene expression profiles of the lung tissue showed early activation of interferon responses and subsequent expression of inflammation-related genes that coincided with the clinical deterioration. Additionally, the lung tissue showed unchanged levels of lymphocyte markers and progressive downregulation of cell cycle genes and extracellular matrix components. Infection in the brain resulted in a limited breadth of the host responses, which is in accordance with the immunoprivileged status of this organ. Finally, we propose a model of the pathogenic mechanisms of henipavirus infection that integrates multiple components of the host responses.",2018 Mar 14,"['Leon, Alberto J.', 'Borisevich, Viktoriya', 'Boroumand, Nahal', 'Seymour, Robert', 'Nusbaum, Rebecca', 'Escaffre, Olivier', 'Xu, Luoling', 'Kelvin, David J.', 'Rockx, Barry']",PLoS Negl Trop Dis,,,True
b2ffe7f0bedb7b3ab6d0181ec70ece3e4e2dabea,PMC,Type I interferon receptor knockout mice as models for infection of highly pathogenic viruses with outbreak potential,http://dx.doi.org/10.24272/j.issn.2095-8137.2017.052,PMC5869239,29511140,CC BY,"Due to their inability to generate a complete immune response, mice knockout for type I interferon (IFN) receptors (Ifnar(–/–)) are more susceptible to viral infections, and are thus commonly used for pathogenesis studies. This mouse model has been used to study many diseases caused by highly pathogenic viruses from many families, including the Flaviviridae, Filoviridae, Arenaviridae, Bunyaviridae, Henipaviridae, and Togaviridae. In this review, we summarize the findings from these animal studies, and discuss the pros and cons of using this model versus other known methods for studying pathogenesis in animals.",2018 Jan 18,"['Wong, Gary', 'Qiu, Xiang-Guo']",Zool Res,,,True
5669349639eae4f58b4fecca26fcc271094c70ba,PMC,Detection and Characterization of Homologues of Human Hepatitis Viruses and Pegiviruses in Rodents and Bats in Vietnam,http://dx.doi.org/10.3390/v10030102,PMC5869495,29495551,CC BY,"Rodents and bats are now widely recognised as important sources of zoonotic virus infections in other mammals, including humans. Numerous surveys have expanded our knowledge of diverse viruses in a range of rodent and bat species, including their origins, evolution, and range of hosts. In this study of pegivirus and human hepatitis-related viruses, liver and serum samples from Vietnamese rodents and bats were examined by PCR and sequencing. Nucleic acids homologous to human hepatitis B, C, E viruses were detected in liver samples of 2 (1.3%) of 157 bats, 38 (8.1%), and 14 (3%) of 470 rodents, respectively. Hepacivirus-like viruses were frequently detected (42.7%) in the bamboo rat, Rhizomys pruinosus, while pegivirus RNA was only evident in 2 (0.3%) of 638 rodent serum samples. Complete or near-complete genome sequences of HBV, HEV and pegivirus homologues closely resembled those previously reported from rodents and bats. However, complete coding region sequences of the rodent hepacivirus-like viruses substantially diverged from all of the currently classified variants and potentially represent a new species in the Hepacivirus genus. Of the viruses identified, their routes of transmission and potential to establish zoonoses remain to be determined.",2018 Feb 28,"['Van Nguyen, Dung', 'Van Nguyen, Cuong', 'Bonsall, David', 'Ngo, Tue Tri', 'Carrique-Mas, Juan', 'Pham, Anh Hong', 'Bryant, Juliet E.', 'Thwaites, Guy', 'Baker, Stephen', 'Woolhouse, Mark', 'Simmonds, Peter']",Viruses,,,True
c0b11b19a87de55ec7803cad2e855942ce498d6b,PMC,Oral Immunization against PEDV with Recombinant Lactobacillus casei Expressing Dendritic Cell-Targeting Peptide Fusing COE Protein of PEDV in Piglets,http://dx.doi.org/10.3390/v10030106,PMC5869499,29494530,CC BY,"Porcine epidemic diarrhea (PED) is a highly contagious disease in newborn piglets. In our previous study, a genetically engineered Lactobacillus casei oral vaccine (pPG-COE-DCpep/L393) expressing a dendritic cell (DC)-targeting peptide fused with porcine epidemic diarrhea virus (PEDV) COE antigen was developed. This vaccine induced significant levels of anti-PEDV specific IgG and IgA antibody responses in mice, indicating a potential strategy against PEDV infection. In this study, pPG-COE-DCpep/L393 was used for oral vaccination of newborn piglets against PEDV. We then assessed the immune responses and protection efficacy of pPG-COE-DCpep/L393. An indirect enzyme-linked immunosorbent assay (ELISA) showed that the recombinant Lactobacillus vaccine elicits a specific systemic and mucosal immune response. The T-helper cells mediated by pPG-COE-DCpep/L393 and PEDV infection display a Th1 phenotype. The histopathological results showed that pPG-COE-DCpep/L393 promotes lymphocyte proliferation and effectively protects piglets against PEDV infection. The transforming growth factor-β level indicated that the recombinant Lactobacillus vaccine plays a role in anti-inflammatory responses in mesenteric lymph nodes during PEDV infection. These results show that pPG-COE-DCpep/L393 is a potential vaccine against PEDV infection.",2018 Mar 1,"['Hou, Xingyu', 'Jiang, Xinpeng', 'Jiang, Yanping', 'Tang, Lijie', 'Xu, Yigang', 'Qiao, Xinyuan', 'Liu, Min', 'Cui, Wen', 'Ma, Guangpeng', 'Li, Yijing']",Viruses,,,True
c9df636e3e64891968ab4052a6fb6d20e95b1a2b,PMC,Cellular hnRNP A1 Interacts with Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus and Impairs Viral Replication,http://dx.doi.org/10.3390/v10030127,PMC5869520,29534017,CC BY,"The nucleocapsid (N) protein is a major structural component of porcine epidemic diarrhea virus (PEDV), which is predicted to be a multifunctional protein in viral replication. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a cellular protein participating in the splicing of pre-mRNA in the nucleus and translation regulation in the cytoplasm. According to our previous proteomic study about PEDV infection in vivo, hnRNP A1 was thought to be a cellular factor influencing PEDV replication. In this report, PEDV N protein was discovered to colocalize with cellular hnRNP A1 in perinuclear region of PEDV infected cells. Co-immunoprecipitation (CO-IP) results clearly demonstrated that PEDV N protein could bind to human hnRNP A1. Replication of PEDV was inhibited by silencing the expression of hnRNP A1 in CCL-81 cells, suggesting the positive effect of hnRNP A1 on PEDV infection.",2018 Mar 13,"['Li, Zhonghua', 'Zeng, Wei', 'Ye, Shiyi', 'Lv, Jian', 'Nie, Axiu', 'Zhang, Bingzhou', 'Sun, Yumei', 'Han, Heyou', 'He, Qigai']",Viruses,,,True
e741dab28c2359000a1069189b3879c97f2f83ad,PMC,Alphavirus Nucleocapsid Packaging and Assembly,http://dx.doi.org/10.3390/v10030138,PMC5869531,29558394,CC BY,"Alphavirus nucleocapsids are assembled in the cytoplasm of infected cells from 240 copies of the capsid protein and the approximately 11 kb positive strand genomic RNA. However, the challenge of how the capsid specifically selects its RNA package and assembles around it has remained an elusive one to solve. In this review, we will summarize what is known about the alphavirus capsid protein, the packaging signal, and their roles in the mechanism of packaging and assembly. We will review the discovery of the packaging signal and how there is as much evidence for, as well as against, its requirement to specify packaging of the genomic RNA. Finally, we will compare this model with those of other viral systems including particular reference to a relatively new idea of RNA packaging based on the presence of multiple minimal packaging signals throughout the genome known as the two stage mechanism. This review will provide a basis for further investigating the fundamental ways of how RNA viruses are able to select their own cargo from the relative chaos that is the cytoplasm.",2018 Mar 20,"['Mendes, Adriano', 'Kuhn, Richard J.']",Viruses,,,True
3c67252392670f7eb8bd7ec3c01daf8e2b3a6da9,PMC,Activation of the c-Jun NH(2)-terminal kinase pathway by coronavirus infectious bronchitis virus promotes apoptosis independently of c-Jun,http://dx.doi.org/10.1038/s41419-017-0053-0,PMC5870581,29238080,CC BY,"Mitogen-activated protein kinases (MAPKs) are conserved protein kinases that regulate a variety of important cellular signaling pathways. Among them, c-Jun N-terminal kinases (JNK) are known to be activated by various environmental stresses including virus infections. Previously, activation of the JNK pathway has been detected in cells infected with several coronaviruses. However, detailed characterization of the pathway as well as its implication in host–virus interactions has not been fully investigated. Here we report that the JNK pathway was activated in cells infected with the avian coronavirus infectious bronchitis virus (IBV). Of the two known upstream MAPK kinases (MKK), MKK7, but not MKK4, was shown to be responsible for IBV-induced JNK activation. Moreover, knockdown and overexpression experiments demonstrated that JNK served as a pro-apoptotic protein during IBV infection. Interestingly, pro-apoptotic activity of JNK was not mediated via c-Jun, but involved modulation of the anti-apoptotic protein B-cell lymphoma 2 (Bcl2). Taken together, JNK constitutes an important aspect of coronavirus–host interaction, along with other MAPKs.",2017 Dec 13,"['Fung, To Sing', 'Liu, Ding Xiang']",Cell Death Dis,,,True
30420a081a88b98988e277a508b07af7e7acde41,PMC,Genome-wide analysis of codon usage bias in four sequenced cotton species,http://dx.doi.org/10.1371/journal.pone.0194372,PMC5870960,29584741,CC BY,"Codon usage bias (CUB) is an important evolutionary feature in a genome which provides important information for studying organism evolution, gene function and exogenous gene expression. The CUB and its shaping factors in the nuclear genomes of four sequenced cotton species, G. arboreum (A(2)), G. raimondii (D(5)), G. hirsutum (AD(1)) and G. barbadense (AD(2)) were analyzed in the present study. The effective number of codons (ENC) analysis showed the CUB was weak in these four species and the four subgenomes of the two tetraploids. Codon composition analysis revealed these four species preferred to use pyrimidine-rich codons more frequently than purine-rich codons. Correlation analysis indicated that the base content at the third position of codons affect the degree of codon preference. PR2-bias plot and ENC-plot analyses revealed that the CUB patterns in these genomes and subgenomes were influenced by combined effects of translational selection, directional mutation and other factors. The translational selection (P2) analysis results, together with the non-significant correlation between GC12 and GC3, further revealed that translational selection played the dominant role over mutation pressure in the codon usage bias. Through relative synonymous codon usage (RSCU) analysis, we detected 25 high frequency codons preferred to end with T or A, and 31 low frequency codons inclined to end with C or G in these four species and four subgenomes. Finally, 19 to 26 optimal codons with 19 common ones were determined for each species and subgenomes, which preferred to end with A or T. We concluded that the codon usage bias was weak and the translation selection was the main shaping factor in nuclear genes of these four cotton genomes and four subgenomes.",2018 Mar 27,"['Wang, Liyuan', 'Xing, Huixian', 'Yuan, Yanchao', 'Wang, Xianlin', 'Saeed, Muhammad', 'Tao, Jincai', 'Feng, Wei', 'Zhang, Guihua', 'Song, Xianliang', 'Sun, Xuezhen']",PLoS One,,,True
61022af06d0f830787f610e94f66ca49343c3de2,PMC,Development and evaluation of a novel high-throughput image-based fluorescent neutralization test for detection of Zika virus infection,http://dx.doi.org/10.1371/journal.pntd.0006342,PMC5871014,29543803,CC BY,"Zika virus (ZIKV) is an emerging arbovirus belonging to the genus flavivirus that comprises other important public health viruses, such as dengue (DENV) and yellow fever (YFV). In general, ZIKV infection is a self-limiting disease, however cases of Guillain-Barré syndrome and congenital brain abnormalities in newborn infants have been reported. Diagnosing ZIKV infection remains a challenge, as viral RNA detection is only applicable until a few days after the onset of symptoms. After that, serological tests must be applied, and, as expected, high cross-reactivity between ZIKV and other flavivirus serology is observed. Plaque reduction neutralization test (PRNT) is indicated to confirm positive samples for being more specific, however it is laborious intensive and time consuming, representing a major bottleneck for patient diagnosis. To overcome this limitation, we developed a high-throughput image-based fluorescent neutralization test for ZIKV infection by serological detection. Using 226 human specimens, we showed that the new test presented higher throughput than traditional PRNT, maintaining the correlation between results. Furthermore, when tested with dengue virus samples, it showed 50.53% less cross reactivity than MAC-ELISA. This fluorescent neutralization test could be used for clinical diagnosis confirmation of ZIKV infection, as well as for vaccine clinical trials and seroprevalence studies.",2018 Mar 15,"['Koishi, Andrea Cristine', 'Suzukawa, Andréia Akemi', 'Zanluca, Camila', 'Camacho, Daria Elena', 'Comach, Guillermo', 'Duarte dos Santos, Claudia Nunes']",PLoS Negl Trop Dis,,,True
88836be43482650dfdb4fc0cc47ca6e2d6afd759,PMC,Eyeing up the Future of the Pupillary Light Reflex in Neurodiagnostics,http://dx.doi.org/10.3390/diagnostics8010019,PMC5872002,29534018,CC BY,"The pupillary light reflex (PLR) describes the constriction and subsequent dilation of the pupil in response to light as a result of the antagonistic actions of the iris sphincter and dilator muscles. Since these muscles are innervated by the parasympathetic and sympathetic nervous systems, respectively, different parameters of the PLR can be used as indicators for either sympathetic or parasympathetic modulation. Thus, the PLR provides an important metric of autonomic nervous system function that has been exploited for a wide range of clinical applications. Measurement of the PLR using dynamic pupillometry is now an established quantitative, non-invasive tool in assessment of traumatic head injuries. This review examines the more recent application of dynamic pupillometry as a diagnostic tool for a wide range of clinical conditions, varying from neurodegenerative disease to exposure to toxic chemicals, as well as its potential in the non-invasive diagnosis of infectious disease.",2018 Mar 13,"['Hall, Charlotte A.', 'Chilcott, Robert P.']",Diagnostics (Basel),,,True
7816cee86e3c9d98dd7e426eb7b842918d36f0f1,PMC,Building a global atlas of zoonotic viruses,http://dx.doi.org/10.2471/BLT.17.205005,PMC5872013,29695886,CC BY,,2018 Apr 1,"['Carroll, Dennis', 'Watson, Brooke', 'Togami, Eri', 'Daszak, Peter', 'Mazet, Jonna AK', 'Chrisman, Cara J', 'Rubin, Edward M', 'Wolfe, Nathan', 'Morel, Carlos M', 'Gao, George F', 'Burci, Gian Luca', 'Fukuda, Keiji', 'Auewarakul, Prasert', 'Tomori, Oyewale']",Bull World Health Organ,,,True
bcd61a98bcf6ab96b5e65dd3f7bfe288e6f9153a,PMC,"Stimulation of Dectin-1 and Dectin-2 during Parenteral Immunization, but Not Mincle, Induces Secretory IgA in Intestinal Mucosa",http://dx.doi.org/10.1155/2018/3835720,PMC5872666,29725603,CC BY,"Induction of a robust and long-lived mucosal immune response during vaccination is critical to achieve protection against numerous pathogens. However, traditional injected vaccines are generally poor inducers of mucosal immunity. One of the effective strategies to improve vaccine efficacy is incorporation of adjuvant molecules that enhance and polarize adaptive immune reactions. Effects of Syk-coupled lectin receptor agonists as adjuvants to induce mucosal immune reactions during parenteral immunization are not fully studied. We now report that the agonists trehalose-6,6-dibehenate (TDB), curdlan, and furfurman, which stimulate Dectin-1, Dectin-2, and Mincle, respectively, activate transcription factors (NF-κB, NFAT, and AP-1) to various extents in murine RAW 264.7 macrophages, even though similar pathways are activated. The agonists also elicit differential expression of maturation markers in bone marrow-derived dendritic cells, as well as differential cytokine secretion from these cells and from splenic mononuclear cells. In vivo assays also show that agonists of Dectin-1 and Dectin-2, but not Mincle, induce heavy IgA secretion in intestinal mucosa even when delivered parenterally. Strikingly, this effect appears to be formulation-independent. Collectively, the data suggest that adjuvants based on Dectin-1 and Dectin-2 agonists may significantly improve the efficacy of parenteral vaccines by inducing robust local immune reactions in intestinal mucosa.",2018 Mar 14,"['Dzharullaeva, Alina S.', 'Tukhvatulin, Amir I.', 'Erokhova, Alina S.', 'Bandelyuk, Alina S.', 'Polyakov, Nikita B.', 'Solovyev, Andrey I.', 'Nikitenko, Natalia A.', 'Shcheblyakov, Dmitry V.', 'Naroditsky, Boris S.', 'Logunov, Denis Y.', 'Gintsburg, Alexander L.']",J Immunol Res,,,True
af9351df01b33367dfa54a78aebf48943c902618,PMC,Rapid detection of potyviruses from crude plant extracts,http://dx.doi.org/10.1016/j.ab.2018.01.019,PMC5873530,29378167,CC BY,"Potyviruses (genus Potyvirus; family Potyviridae) are widely distributed and represent one of the most economically important genera of plant viruses. Therefore, their accurate detection is a key factor in developing efficient control strategies. However, this can sometimes be problematic particularly in plant species containing high amounts of polysaccharides and polyphenols such as yam (Dioscorea spp.). Here, we report the development of a reliable, rapid and cost-effective detection method for the two most important potyviruses infecting yam based on reverse transcription-recombinase polymerase amplification (RT-RPA). The developed method, named ‘Direct RT-RPA’, detects each target virus directly from plant leaf extracts prepared with a simple and inexpensive extraction method avoiding laborious extraction of high-quality RNA. Direct RT-RPA enables the detection of virus-positive samples in under 30 min at a single low operation temperature (37 °C) without the need for any expensive instrumentation. The Direct RT-RPA tests constitute robust, accurate, sensitive and quick methods for detection of potyviruses from recalcitrant plant species. The minimal sample preparation requirements and the possibility of storing RPA reagents without cold chain storage, allow Direct RT-RPA to be adopted in minimally equipped laboratories and with potential use in plant clinic laboratories and seed certification facilities worldwide.",2018 Apr 1,"['Silva, Gonçalo', 'Oyekanmi, Joshua', 'Nkere, Chukwuemeka K.', 'Bömer, Moritz', 'Kumar, P. Lava', 'Seal, Susan E.']",Anal Biochem,,,False
dc1a1a0fec049e850789175fe06b1453c9114c62,PMC,Skipping Multiple Exons to Treat DMD—Promises and Challenges,http://dx.doi.org/10.3390/biomedicines6010001,PMC5874658,29301272,CC BY,"Duchenne muscular dystrophy (DMD) is a lethal disorder caused by mutations in the DMD gene. Antisense-mediated exon-skipping is a promising therapeutic strategy that makes use of synthetic nucleic acids to skip frame-disrupting exon(s) and allows for short but functional protein expression by restoring the reading frame. In 2016, the U.S. Food and Drug Administration (FDA) approved eteplirsen, which skips DMD exon 51 and is applicable to approximately 13% of DMD patients. Multiple exon skipping, which is theoretically applicable to 80–90% of DMD patients in total, have been demonstrated in animal models, including dystrophic mice and dogs, using cocktail antisense oligonucleotides (AOs). Although promising, current drug approval systems pose challenges for the use of a cocktail AO. For example, both exons 6 and 8 need to be skipped to restore the reading frame in dystrophic dogs. Therefore, the cocktail of AOs targeting these exons has a combined therapeutic effect and each AO does not have a therapeutic effect by itself. The current drug approval system is not designed to evaluate such circumstances, which are completely different from cocktail drug approaches in other fields. Significant changes are needed in the drug approval process to promote the cocktail AO approach.",2018 Jan 2,"['Aslesh, Tejal', 'Maruyama, Rika', 'Yokota, Toshifumi']",Biomedicines,,,True
0db6ae77cd580f4e8c3cb6728de4a2a6197a727c,PMC,In Vivo Characterisation of Five Strains of Bovine Viral Diarrhoea Virus 1 (Subgenotype 1c),http://dx.doi.org/10.3390/pathogens7010012,PMC5874738,29351201,CC BY,"Bovine viral diarrhoea virus 1 (BVDV-1) is strongly associated with several important diseases of cattle, such as bovine respiratory disease, diarrhoea and haemoragic lesions. To date many subgenotypes have been reported for BVDV-1, currently ranging from subgenotype 1a to subgenotype 1u. While BVDV-1 has a world-wide distribution, the subgenotypes have a more restricted geographical distribution. As an example, BVDV-1 subgenotypes 1a and 1b are frequently detected in North America and Europe, while the subgenotype 1c is rarely detected. In contrast, BVDV-1 subgenotype 1c is by far the most commonly reported in Australia. Despite this, uneven distribution of the biological importance of the subgenotypes remains unclear. The aim of this study was to characterise the in vivo properties of five strains of BVDV-1 subgenotype 1c in cattle infection studies. No overt respiratory signs were reported in any of the infected cattle regardless of strain. Consistent with other subgenotypes, transient pyrexia and leukopenia were commonly identified, while thrombocytopenia was not. The quantity of virus detected in the nasal secretions of transiently infected animals suggested the likelihood of horizontal transmission was very low. Further studies are required to fully understand the variability and importance of the BVDV-1 subgenotype 1c.",2018 Jan 19,"['Ambrose, Rebecca K.', 'Gravel, Jennifer L.', 'Commins, Margaret A.', 'Fowler, Elizabeth V.', 'Mahony, Timothy J.']",Pathogens,,,True
f7658f780f7b559a2ddb1649957efda8a94f534b,PMC,"Species C Rotaviruses in Children with Diarrhea in India, 2010–2013: A Potentially Neglected Cause of Acute Gastroenteritis",http://dx.doi.org/10.3390/pathogens7010023,PMC5874749,29462971,CC BY,"All over the world, children and adults are severely affected by acute gastroenteritis, caused by one of the emerging enteric pathogens, rotavirus C (RVC). At present, no extensive surveillance program is running for RVC in India, and its prevalence is largely unknown except cases of local outbreaks. Here, we intended to detect the presence of RVC in diarrheic children visiting or admitted to hospitals in Haldwani (state of Uttarakhand, India), a city located in the foothills of the Himalayas. During 2010–2013, we screened 119 samples for RVC by an RVC VP6 gene-specific RT-PCR. Of these, 38 (31.93%) were found positive, which is higher than the incidence rates reported so far from India. The phylogenetic analysis of the derived nucleotide sequences from one of the human RVC (HuRVC) isolates, designated as HuRVC/H28/2013/India, showed that the study isolate belongs to genotype I2, P2 and E2 for RVC structural genes 6 and 4 (VP6, and VP4) and non-structural gene 4 (NSP4), respectively. Furthermore, the VP6 gene of HuRVC/H28/2013/India shows the highest similarity to a recently-reported human-like porcine RVC (PoRVC/ASM140/2013/India, KT932963) from India suggesting zoonotic transmission. We also report a full-length NSP4 gene sequence of human RVC from India. Under the One-health platforms there is a need to launch combined human and animal RVC surveillance programs for a better understanding of the epidemiology of RVC infections and for implementing control strategies.",2018 Feb 17,"['Bhat, Sudipta', 'Kattoor, Jobin Jose', 'Malik, Yashpal Singh', 'Sircar, Shubhankar', 'Deol, Pallavi', 'Rawat, Vinita', 'Rakholia, Ritu', 'Ghosh, Souvik', 'Vlasova, Anastasia N.', 'Nadia, Touil', 'Dhama, Kuldeep', 'Kobayashi, Nobumichi']",Pathogens,,,True
6e0d5cb338ea8a2916c74b3b06789d3b21ac36a4,PMC,"Insights into DNA substrate selection by APOBEC3G from structural, biochemical, and functional studies",http://dx.doi.org/10.1371/journal.pone.0195048,PMC5875850,29596531,CC0,"Human apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3 (A3) proteins are a family of cytidine deaminases that catalyze the conversion of deoxycytidine (dC) to deoxyuridine (dU) in single-stranded DNA (ssDNA). A3 proteins act in the innate immune response to viral infection by mutating the viral ssDNA. One of the most well-studied human A3 family members is A3G, which is a potent inhibitor of HIV-1. Each A3 protein prefers a specific substrate sequence for catalysis—for example, A3G deaminates the third dC in the CCCA sequence motif. However, the interaction between A3G and ssDNA is difficult to characterize due to poor solution behavior of the full-length protein and loss of DNA affinity of the truncated protein. Here, we present a novel DNA-anchoring fusion strategy using the protection of telomeres protein 1 (Pot1) which has nanomolar affinity for ssDNA, with which we captured an A3G-ssDNA interaction. We crystallized a non-preferred adenine in the -1 nucleotide-binding pocket of A3G. The structure reveals a unique conformation of the catalytic site loops that sheds light onto how the enzyme scans substrate in the -1 pocket. Furthermore, our biochemistry and virology studies provide evidence that the nucleotide-binding pockets on A3G influence each other in selecting the preferred DNA substrate. Together, the results provide insights into the mechanism by which A3G selects and deaminates its preferred substrates and help define how A3 proteins are tailored to recognize specific DNA sequences. This knowledge contributes to a better understanding of the mechanism of DNA substrate selection by A3G, as well as A3G antiviral activity against HIV-1.",2018 Mar 29,"['Ziegler, Samantha J.', 'Liu, Chang', 'Landau, Mark', 'Buzovetsky, Olga', 'Desimmie, Belete A.', 'Zhao, Qi', 'Sasaki, Tomoaki', 'Burdick, Ryan C.', 'Pathak, Vinay K.', 'Anderson, Karen S.', 'Xiong, Yong']",PLoS One,,,True
d1232afc1f36390f6834e4627d99db439020be56,PMC,Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells,http://dx.doi.org/10.3389/fimmu.2018.00493,PMC5876289,29628923,CC BY,"Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα) as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1) specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs) were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires.",2018 Mar 23,"['Correa, Isabel', 'Ilieva, Kristina M.', 'Crescioli, Silvia', 'Lombardi, Sara', 'Figini, Mariangela', 'Cheung, Anthony', 'Spicer, James F.', 'Tutt, Andrew N. J.', 'Nestle, Frank O.', 'Karagiannis, Panagiotis', 'Lacy, Katie E.', 'Karagiannis, Sophia N.']",Front Immunol,,,True
68c9e356d0a2c9f60cd7a48356df0670d99b59d5,PMC,"A Review of Eight High-Priority, Economically Important Viral Pathogens of Poultry within the Caribbean Region",http://dx.doi.org/10.3390/vetsci5010014,PMC5876562,29373488,CC BY,"Viral pathogens cause devastating economic losses in poultry industries worldwide. The Caribbean region, which boasts some of the highest rates of poultry consumption in the world, is no exception. This review summarizes evidence for the circulation and spread of eight high-priority, economically important poultry viruses across the Caribbean region. Avian influenza virus (AIV), infectious bronchitis virus (IBV), Newcastle disease virus (NDV), infectious laryngotracheitis virus (ILTV), avian metapneumovirus (aMPV), infectious bursal disease virus (IBDV), fowl adenovirus group 1 (FADV Gp1), and egg drop syndrome virus (EDSV) were selected for review. This review of serological, molecular, and phylogenetic studies across Caribbean countries reveals evidence for sporadic outbreaks of respiratory disease caused by notifiable viral pathogens (AIV, IBV, NDV, and ILTV), as well as outbreaks of diseases caused by immunosuppressive viral pathogens (IBDV and FADV Gp1). This review highlights the need to strengthen current levels of surveillance and reporting for poultry diseases in domestic and wild bird populations across the Caribbean, as well as the need to strengthen the diagnostic capacity and capability of Caribbean national veterinary diagnostic laboratories.",2018 Jan 26,"['Brown Jordan, Arianne', 'Gongora, Victor', 'Hartley, Dane', 'Oura, Christopher']",Vet Sci,,,True
b1d5a591bff2740b3b81dce8659fec2470ac9dfb,PMC,Stability of Porcine Epidemic Diarrhea Virus on Fomite Materials at Different Temperatures,http://dx.doi.org/10.3390/vetsci5010021,PMC5876564,29438310,CC BY,"Indirect transmission of porcine epidemic diarrhea virus (PEDV) ensues when susceptible animals contact PEDV-contaminated fomite materials. Although the survival of PEDV under various pHs and temperatures has been studied, virus stability on different fomite surfaces under varying temperature conditions has not been explored. Hence, we evaluated the survival of PEDV on inanimate objects routinely used on swine farms such as styrofoam, rubber, plastic, coveralls, and other equipment. The titer of infectious PEDV at 4 °C decreased by only 1 to 2 log during the first 5 days, and the virus was recoverable for up to 15 days on Styrofoam, aluminum, Tyvek(®) coverall, cloth, and plastic. However, viral titers decreased precipitously when stored at room temperature; no virus was detectable after one day on all materials tested. A more sensitive immunoplaque assay was able to detect virus from Styrofoam, metal, and plastic at 20 days post application, representing a 3-log loss of input virus on fomite materials. Recovery of infectious PEDV from Tyvek(®) coverall and rubber was above detection limit at 20 days. Our findings indicate that the type of fomite material and temperatures impact PEDV stability, which is important in understanding the nuances of indirect transmission and epidemiology of PEDV.",2018 Feb 13,"['Kim, Yonghyan', 'Krishna, Venkatramana D.', 'Torremorell, Montserrat', 'Goyal, Sagar M.', 'Cheeran, Maxim C.-J.']",Vet Sci,,,True
0a6d27149c1fc958d4f6a598cc165a7cb0ee0185,PMC,Avian Respiratory Coinfection and Impact on Avian Influenza Pathogenicity in Domestic Poultry: Field and Experimental Findings,http://dx.doi.org/10.3390/vetsci5010023,PMC5876583,29495276,CC BY,"The avian respiratory system hosts a wide range of commensal and potential pathogenic bacteria and/or viruses that interact with each other. Such interactions could be either synergistic or antagonistic, which subsequently determines the severity of the disease complex. The intensive rearing methods of poultry are responsible for the marked increase in avian respiratory diseases worldwide. The interaction between avian influenza with other pathogens can guarantee the continuous existence of other avian pathogens, which represents a global concern. A better understanding of the impact of the interaction between avian influenza virus and other avian respiratory pathogens provides a better insight into the respiratory disease complex in poultry and can lead to improved intervention strategies aimed at controlling virus spread.",2018 Feb 24,"['Samy, Ahmed', 'Naguib, Mahmoud M.']",Vet Sci,,,True
a08f5fd1ac9fc3e33a771787d584a845a8558cae,PMC,Case Study of Airborne Pathogen Dispersion Patterns in Emergency Departments with Different Ventilation and Partition Conditions,http://dx.doi.org/10.3390/ijerph15030510,PMC5877055,29534043,CC BY,"The prevention of airborne infections in emergency departments is a very important issue. This study investigated the effects of architectural features on airborne pathogen dispersion in emergency departments by using a CFD (computational fluid dynamics) simulation tool. The study included three architectural features as the major variables: increased ventilation rate, inlet and outlet diffuser positions, and partitions between beds. The most effective method for preventing pathogen dispersion and reducing the pathogen concentration was found to be increasing the ventilation rate. Installing partitions between the beds and changing the ventilation system’s inlet and outlet diffuser positions contributed only minimally to reducing the concentration of airborne pathogens.",2018 Mar 13,"['Cheong, Chang Heon', 'Lee, Seonhye']",Int J Environ Res Public Health,,,True
99035541b28958c03a36978cdff0aa13b7fcd8e8,PMC,Editorial: Zika Virus Research,http://dx.doi.org/10.3389/fneur.2018.00168,PMC5877197,29628908,CC BY,,2018 Mar 23,"['Bueno-Marí, Rubén', 'Saiz, Juan-Carlos', 'Salomón, Oscar D.', 'Villamil-Jiménez, Luis C.', 'Heukelbach, Jorg', 'Alencar, Carlos H.', 'Armstrong, Paul K.', 'Rosado-de-Castro, Paulo H.', 'Pimentel-Coelho, Pedro M.']",Front Neurol,,,True
820acf55c4e52411482f6eb44360ffa35288b89a,PMC,"Risk factors for hematemesis in Hoima and Buliisa Districts, Western Uganda, September-October 2015",http://dx.doi.org/10.11604/pamj.2017.28.215.12395,PMC5878846,29610653,CC BY,"INTRODUCTION: On 17 September 2015, Buliisa District Health Office reported multiple deaths due to haemorrhage to the Uganda Ministry of Health. We conducted an investigation to verify the existence of an outbreak and to identify the disease nature, mode of transmission and risk factors. METHODS: We defined a suspected case as onset of hematemesis between 1 June 2015 and 15 October 2015 in a resident of Hoima, Buliisa or neighbouring districts. We identified cases by reviewing medical records and actively searching in the community. We interviewed case-patients and health-care workers and performed descriptive epidemiology to generate hypotheses on possible exposures. In a case-control study we compared exposures between 21 cases and 81 controls, matched by age (± 10 years), sex and village of residence. We collected 22 biological specimens from 19 case-patients to test for Viral Haemorrhagic Fevers (VHF). We analysed the data using the Mantel-Haenszel method to account for the matched study design. RESULTS: We identified 56 cases with onset from June to October (attack rate 15/100,000 in Buliisa District and 5.2/100,000 in Hoima District). The age-specific attack rate was highest in persons aged 31-60 years (15/100,000 in Hoima and 47/100,000 in Buliisa); no persons below 15 years of age had the illness. In the case-control study, 42% (5/12) of cases vs. 0.0% (0/77) of controls had liver disease (OR(M-H) = ∞; 95%CI = 3.7-∞); 71% (10/14) of cases vs. 35% (28/81) of controls had ulcer disease (OR(M-H) = 13; 95% CI = 1.6-98); 27% (3/11) of cases vs. 14% (11/81) of controls used indomethacin prior to disease onset (OR(M-H) = 6.0; 95% CI = 1.0-36). None of the blood samples were positive for any of the VHFs. CONCLUSION: This reported cluster of hematemesis illness was due to predisposing conditions and use of Non-Steroidal Anti-inflammatory Drugs (NSAID). Health education should be conducted on the danger of NSAIDs misuse, especially in persons with pre-disposing conditions.",2017 Nov 8,"['Kabwama, Steven Ndugwa', 'Mafigiri, Richardson', 'Balinandi, Stephen', 'Kagirita, Atek', 'Riolexus, Alex Ario', 'Zhu, Bao-Ping']",Pan Afr Med J,,,True
3ab8bf523ee26f6e2f7d3cf11d757f8b449d9dcd,PMC,C-Type Lectin Receptors in Antiviral Immunity and Viral Escape,http://dx.doi.org/10.3389/fimmu.2018.00590,PMC5879224,29632536,CC BY,"C-type lectin receptors (CLRs) are important pattern recognition receptors involved in recognition and induction of adaptive immunity to pathogens. Certain CLRs play an important role in viral infections as they efficiently interact with viruses. However, it has become clear that deadly viruses subvert the function of CLRs to escape antiviral immunity and promote infection. In particular, viruses target CLRs to suppress or modulate type I interferons that play a central role in the innate and adaptive defense against viruses. In this review, we discuss the function of CLRs in binding to enveloped viruses like HIV-1 and Dengue virus, and how uptake and signaling cascades have decisive effects on the outcome of infection.",2018 Mar 26,"['Bermejo-Jambrina, Marta', 'Eder, Julia', 'Helgers, Leanne C.', 'Hertoghs, Nina', 'Nijmeijer, Bernadien M.', 'Stunnenberg, Melissa', 'Geijtenbeek, Teunis B. H.']",Front Immunol,,,True
f837cfe73ee695265382ec9873726fcd7b24d9b1,PMC,Airway disease phenotypes in animal models of cystic fibrosis,http://dx.doi.org/10.1186/s12931-018-0750-y,PMC5879563,29609604,CC BY,"In humans, cystic fibrosis (CF) lung disease is characterised by chronic infection, inflammation, airway remodelling, and mucus obstruction. A lack of pulmonary manifestations in CF mouse models has hindered investigations of airway disease pathogenesis, as well as the development and testing of potential therapeutics. However, recently generated CF animal models including rat, ferret and pig models demonstrate a range of well characterised lung disease phenotypes with varying degrees of severity. This review discusses the airway phenotypes of currently available CF animal models and presents potential applications of each model in airway-related CF research.",2018 Apr 2,"['McCarron, Alexandra', 'Donnelley, Martin', 'Parsons, David']",Respir Res,,,True
ff983b21fe80f1f3bf064a3cbc564b63111cadf5,PMC,Adequacy of public health communications on H7N9 and MERS in Singapore: insights from a community based cross-sectional study,http://dx.doi.org/10.1186/s12889-018-5340-x,PMC5879609,29609573,CC BY,"BACKGROUND: Singapore remains vulnerable to worldwide epidemics due to high air traffic with other countries This study aims to measure the public’s awareness of the Middle East Respiratory Syndrome (MERS) and Avian Influenza A (H7N9), identify population groups who are uninformed or misinformed about the diseases, understand their choice of outbreak information source, and assess the effectiveness of communication channels in Singapore. METHODS: A cross-sectional study, comprising of face-to-face interviews, was conducted between June and December 2013 to assess the public’s awareness and knowledge of MERS and H7N9, including their choice of information source. Respondents were randomly selected and recruited from 3 existing cohort studies. An opportunistic sampling approach was also used to recruit new participants or members in the same household through referrals from existing participants. RESULTS: Out of 2969 participants, 53.2% and 79.4% were not aware of H7N9 and MERS respectively. Participants who were older and better educated were most likely to hear about the diseases. The mean total knowledge score was 9.2 (S.D ± 2.3) out of 20, and 5.9 (S.D ± 1.2) out of 10 for H7N9 and MERS respectively. Participants who were Chinese, more educated and older had better knowledge of the diseases. Television and radio were the primary sources of outbreak information regardless of socio-demographic factors. CONCLUSION: Heightening education of infectious outbreaks through appropriate media to the young and less educated could increase awareness.",2018 Apr 2,"['Hou, Yan’an', 'Tan, Yi-roe', 'Lim, Wei Yen', 'Lee, Vernon', 'Tan, Linda Wei Lin', 'Chen, Mark I-Cheng', 'Yap, Peiling']",BMC Public Health,,,True
2f071bf96a0a2a1c4fc270a41ca7f4535f474ec5,PMC,Predicting the effects of parasite co-infection across species boundaries,http://dx.doi.org/10.1098/rspb.2017.2610,PMC5879626,29540516,CC BY,"It is normal for hosts to be co-infected by parasites. Interactions among co-infecting species can have profound consequences, including changing parasite transmission dynamics, altering disease severity and confounding attempts at parasite control. Despite the importance of co-infection, there is currently no way to predict how different parasite species may interact with one another, nor the consequences of those interactions. Here, we demonstrate a method that enables such prediction by identifying two nematode parasite groups based on taxonomy and characteristics of the parasitological niche. From an understanding of the interactions between the two defined groups in one host system (wild rabbits), we predict how two different nematode species, from the same defined groups, will interact in co-infections in a different host system (sheep), and then we test this experimentally. We show that, as predicted, in co-infections, the blood-feeding nematode Haemonchus contortus suppresses aspects of the sheep immune response, thereby facilitating the establishment and/or survival of the nematode Trichostrongylus colubriformis; and that the T. colubriformis-induced immune response negatively affects H. contortus. This work is, to our knowledge, the first to use empirical data from one host system to successfully predict the specific outcome of a different co-infection in a second host species. The study therefore takes the first step in defining a practical framework for predicting interspecific parasite interactions in other animal systems.",2018 Mar 14,"['Lello, Joanne', 'McClure, Susan J.', 'Tyrrell, Kerri', 'Viney, Mark E.']",Proc Biol Sci,,,True
0a01f5cf1c5cdc2711bcef74315dc54a6e143df0,PMC,Proteomic fingerprinting in HIV/HCV co-infection reveals serum biomarkers for the diagnosis of fibrosis staging,http://dx.doi.org/10.1371/journal.pone.0195148,PMC5880398,29608613,CC BY,"BACKGROUND: Hepatic complications of hepatitis C virus (HCV), including fibrosis and cirrhosis are accelerated in human immunodeficiency virus (HIV)-infected individuals. Although, liver biopsy remains the gold standard for staging HCV-associated liver disease, this test can result in serious complications and is subject to sampling errors. These challenges have prompted a search for non-invasive methods for liver fibrosis staging. To this end, we compared serum proteome profiles at different stages of fibrosis in HIV/HCV co- and HCV mono-infected patients using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS). METHODS: Sera from 83 HIV/HCV co- and 68 HCV mono-infected subjects in 4 stages of fibrosis were tested. Sera were fractionated, randomly applied to protein chip arrays (IMAC, CM10 and H50) and spectra were generated at low and high laser intensities. RESULTS: Sixteen biomarkers achieved a p value < 0.01 (ROC values > 0.75 or < 0.25) predictive of fibrosis status in co-infected individuals and 14 in mono infected subjects. Five of these candidate biomarkers contributed to both mono- and co-infected subjects. Candidate diagnostic algorithms were created to distinguish between non-fibrotic and fibrotic individuals using a panel of 4 biomarker peaks. CONCLUSION: These data suggest that SELDI MS profiling can identify diagnostic serum biomarkers for fibrosis that are both common and distinct in HIV/HCV co-infected and HCV mono-infected individuals.",2018 Apr 2,"['Golizeh, Makan', 'Melendez-Pena, Carlos E.', 'Ward, Brian J.', 'Saeed, Sahar', 'Santamaria, Cynthia', 'Conway, Brian', 'Cooper, Curtis', 'Klein, Marina B.', 'Ndao, Momar', None]",PLoS One,,,True
d4ab193f58a20b66aba4237f8d5f33d023bca4fb,PMC,Xenosurveillance reflects traditional sampling techniques for the identification of human pathogens: A comparative study in West Africa,http://dx.doi.org/10.1371/journal.pntd.0006348,PMC5880402,29561834,CC0,"BACKGROUND: Novel surveillance strategies are needed to detect the rapid and continuous emergence of infectious disease agents. Ideally, new sampling strategies should be simple to implement, technologically uncomplicated, and applicable to areas where emergence events are known to occur. To this end, xenosurveillance is a technique that makes use of blood collected by hematophagous arthropods to monitor and identify vertebrate pathogens. Mosquitoes are largely ubiquitous animals that often exist in sizable populations. As well, many domestic or peridomestic species of mosquitoes will preferentially take blood-meals from humans, making them a unique and largely untapped reservoir to collect human blood. METHODOLOGY/PRINCIPAL FINDINGS: We sought to take advantage of this phenomenon by systematically collecting blood-fed mosquitoes during a field trail in Northern Liberia to determine whether pathogen sequences from blood engorged mosquitoes accurately mirror those obtained directly from humans. Specifically, blood was collected from humans via finger-stick and by aspirating bloodfed mosquitoes from the inside of houses. Shotgun metagenomic sequencing of RNA and DNA derived from these specimens was performed to detect pathogen sequences. Samples obtained from xenosurveillance and from finger-stick blood collection produced a similar number and quality of reads aligning to two human viruses, GB virus C and hepatitis B virus. CONCLUSIONS/SIGNIFICANCE: This study represents the first systematic comparison between xenosurveillance and more traditional sampling methodologies, while also demonstrating the viability of xenosurveillance as a tool to sample human blood for circulating pathogens.",2018 Mar 21,"['Fauver, Joseph R.', 'Weger-Lucarelli, James', 'Fakoli, Lawrence S.', 'Bolay, Kpehe', 'Bolay, Fatorma K.', 'Diclaro, Joseph W.', 'Brackney, Doug E.', 'Foy, Brian D.', 'Stenglein, Mark D.', 'Ebel, Gregory D.']",PLoS Negl Trop Dis,,,True
6a80b22e84d2692545c6f11d7cb4c96602a25c39,PMC,Immune regulation of the unfolded protein response at the mucosal barrier in viral infection,http://dx.doi.org/10.1002/cti2.1014,PMC5881172,29632667,CC BY,"Protein folding in the endoplasmic reticulum (ER) is subject to stringent quality control. When protein secretion demand exceeds the protein folding capacity of the ER, the unfolded protein response (UPR) is triggered as a consequence of ER stress. Due to the secretory function of epithelial cells, UPR plays an important role in maintaining epithelial barrier function at mucosal sites. ER stress and activation of the UPR are natural mechanisms by which mucosal epithelial cells combat viral infections. In this review, we discuss the important role of UPR in regulating mucosal epithelium homeostasis. In addition, we review current insights into how the UPR is involved in viral infection at mucosal barriers and potential therapeutic strategies that restore epithelial cell integrity following acute viral infections via cytokine and cellular stress manipulation.",2018 Apr 3,"['Wang, Ran', 'Moniruzzaman, Md.', 'Shuffle, Eric', 'Lourie, Rohan', 'Hasnain, Sumaira Z']",Clin Transl Immunology,,,True
50f74fde0ed19bb067b5a48ae60a6d00354b1ba7,PMC,Mitigating the risk of Zika virus contamination of raw materials and cell lines in the manufacture of biologicals,http://dx.doi.org/10.1099/jgv.0.000995,PMC5882083,29239715,CC BY,"Ensuring the virological safety of biologicals is challenging due to the risk of viral contamination of raw materials and cell banks, and exposure during in-process handling to known and/or emerging viral pathogens. Viruses may contaminate raw materials and biologicals intended for human or veterinary use and remain undetected until appropriate testing measures are employed. The outbreak and expansive spread of the mosquito-borne flavivirus Zika virus (ZIKV) poses challenges to screening human- and animal -derived products used in the manufacture of biologicals. Here, we report the results of an in vitro study where detector cell lines were challenged with African and Asian lineages of ZIKV. We demonstrate that this pathogen is robustly detectable by in vitro assay, thereby providing assurance of detection of ZIKV, and in turn underpinning the robustness of in vitro virology assays in safety testing of biologicals.",2018 Feb 14,"['Zmurko, Joanna', 'Vasey, Douglas B.', 'Donald, Claire L.', 'Armstrong, Alison A.', 'McKee, Marian L.', 'Kohl, Alain', 'Clayton, Reginald F.']",J Gen Virol,,,True
6eb282b0887ed1a7ab59123919bbadbf9ce6ed55,PMC,Preprints: An underutilized mechanism to accelerate outbreak science,http://dx.doi.org/10.1371/journal.pmed.1002549,PMC5882117,29614073,CC BY,"In an Essay, Michael Johansson and colleagues advocate the posting of research studies addressing infectious disease outbreaks as preprints.",2018 Apr 3,"['Johansson, Michael A.', 'Reich, Nicholas G.', 'Meyers, Lauren Ancel', 'Lipsitch, Marc']",PLoS Med,,,True
c50f579edefdb6e484469d95488c5a2cd3f03135,PMC,Serologic and behavioral risk survey of workers with wildlife contact in China,http://dx.doi.org/10.1371/journal.pone.0194647,PMC5882129,29614074,CC BY,"We report on a study conducted in Guangdong Province, China, to characterize behaviors and perceptions associated with transmission of pathogens with pandemic potential in highly exposed human populations at the animal-human interface. A risk factor/exposure survey was administered to individuals with high levels of exposure to wildlife. Serological testing was performed to evaluate prior infection with several wildlife viral pathogens. Follow up serology was performed on a subset of the cohort as well as close contacts of individuals. 1,312 individuals were enrolled in the study. Contact with a wide range of wildlife species was reported in both occupational and occasional contexts. The overall proportion of individuals seropositive to any of the tested wildlife pathogens was approximately 4.0%. However, persons employed as butchers demonstrated a seropositivity of 9.0% to at least one pathogen of interest. By contrast, individuals working as hunters had lower rates of seropositivity. Among the study population, a number of other behaviors showed correlation with seropositivity, including contact with particular wildlife species such as field rats. These results demonstrate the need to further explore zoonotic risks of particular activities regarding wildlife contact, and to better understand risks of persons working as butchers with wildlife species.",2018 Apr 3,"['Monagin, Corina', 'Paccha, Blanca', 'Liang, Ning', 'Trufan, Sally', 'Zhou, Huiqiong', 'Wu, De', 'Schneider, Bradley S.', 'Chmura, Aleksei', 'Epstein, Jonathan', 'Daszak, Peter', 'Ke, Changwen', 'Rabinowitz, Peter M.']",PLoS One,,,True
df8f60499b2a0ec1e86fa61cbb01f1738afa719c,PMC,Serologic and behavioral risk survey of workers with wildlife contact in China,http://dx.doi.org/10.1371/journal.pone.0194647,PMC5882129,29614074,CC BY,"We report on a study conducted in Guangdong Province, China, to characterize behaviors and perceptions associated with transmission of pathogens with pandemic potential in highly exposed human populations at the animal-human interface. A risk factor/exposure survey was administered to individuals with high levels of exposure to wildlife. Serological testing was performed to evaluate prior infection with several wildlife viral pathogens. Follow up serology was performed on a subset of the cohort as well as close contacts of individuals. 1,312 individuals were enrolled in the study. Contact with a wide range of wildlife species was reported in both occupational and occasional contexts. The overall proportion of individuals seropositive to any of the tested wildlife pathogens was approximately 4.0%. However, persons employed as butchers demonstrated a seropositivity of 9.0% to at least one pathogen of interest. By contrast, individuals working as hunters had lower rates of seropositivity. Among the study population, a number of other behaviors showed correlation with seropositivity, including contact with particular wildlife species such as field rats. These results demonstrate the need to further explore zoonotic risks of particular activities regarding wildlife contact, and to better understand risks of persons working as butchers with wildlife species.",2018 Apr 3,"['Monagin, Corina', 'Paccha, Blanca', 'Liang, Ning', 'Trufan, Sally', 'Zhou, Huiqiong', 'Wu, De', 'Schneider, Bradley S.', 'Chmura, Aleksei', 'Epstein, Jonathan', 'Daszak, Peter', 'Ke, Changwen', 'Rabinowitz, Peter M.']",PLoS One,,,False
5efaa2887e1984141793f83d95ff34641d191b9c,PMC,Serologic and behavioral risk survey of workers with wildlife contact in China,http://dx.doi.org/10.1371/journal.pone.0194647,PMC5882129,29614074,CC BY,"We report on a study conducted in Guangdong Province, China, to characterize behaviors and perceptions associated with transmission of pathogens with pandemic potential in highly exposed human populations at the animal-human interface. A risk factor/exposure survey was administered to individuals with high levels of exposure to wildlife. Serological testing was performed to evaluate prior infection with several wildlife viral pathogens. Follow up serology was performed on a subset of the cohort as well as close contacts of individuals. 1,312 individuals were enrolled in the study. Contact with a wide range of wildlife species was reported in both occupational and occasional contexts. The overall proportion of individuals seropositive to any of the tested wildlife pathogens was approximately 4.0%. However, persons employed as butchers demonstrated a seropositivity of 9.0% to at least one pathogen of interest. By contrast, individuals working as hunters had lower rates of seropositivity. Among the study population, a number of other behaviors showed correlation with seropositivity, including contact with particular wildlife species such as field rats. These results demonstrate the need to further explore zoonotic risks of particular activities regarding wildlife contact, and to better understand risks of persons working as butchers with wildlife species.",2018 Apr 3,"['Monagin, Corina', 'Paccha, Blanca', 'Liang, Ning', 'Trufan, Sally', 'Zhou, Huiqiong', 'Wu, De', 'Schneider, Bradley S.', 'Chmura, Aleksei', 'Epstein, Jonathan', 'Daszak, Peter', 'Ke, Changwen', 'Rabinowitz, Peter M.']",PLoS One,,,False
c0e284c9dd2ca500ae5f10d04d0639d0f8779a16,PMC,Time-series analysis for porcine reproductive and respiratory syndrome in the United States,http://dx.doi.org/10.1371/journal.pone.0195282,PMC5882168,29614099,CC BY,"Industry-driven voluntary disease control programs for swine diseases emerged in North America in the early 2000’s, and, since then, those programs have been used for monitoring diseases of economic importance to swine producers. One example of such initiatives is Dr. Morrison’s Swine Health Monitoring Project, a nation-wide monitoring program for swine diseases including the porcine reproductive and respiratory syndrome (PRRS). PRRS has been extensively reported as a seasonal disease in the U.S., with predictable peaks that start in fall and are extended through the winter season. However, formal time series analysis stratified by geographic region has never been conducted for this important disease across the U.S. The main objective of this study was to use approximately seven years of PRRS incidence data in breeding swine herds to conduct time-series analysis in order to describe the temporal patterns of PRRS outbreaks at the farm level for five major swine-producing states across the U.S. including the states of Minnesota, Iowa, North Carolina, Nebraska and Illinois. Data was aggregated retrospectively at the week level for the number of herds containing animals actively shedding PRRS virus. Basic descriptive statistics were conducted followed by autoregressive integrated moving average (ARIMA) modelling, conducted separately for each of the above-mentioned states. Results showed that there was a difference in the nature of PRRS seasonality among states. Of note, when comparing states, the typical seasonal pattern previously described for PRRS could only be detected for farms located in the states of Minnesota, North Carolina and Nebraska. For the other two states, seasonal peaks every six months were detected within a year. In conclusion, we showed that epidemic patterns are not homogeneous across the U.S, with major peaks of disease occurring through the year. These findings highlight the importance of coordinating alternative control strategies in different regions considering the prevailing epidemiological patterns.",2018 Apr 3,"['Arruda, Andréia Gonçalves', 'Vilalta, Carles', 'Puig, Pere', 'Perez, Andres', 'Alba, Anna']",PLoS One,,,True
9b5d8190f7116da4309ef85c3a3c18d9a4ee75c9,PMC,A Critical Domain of Ebolavirus Envelope Glycoprotein Determines Glycoform and Infectivity,http://dx.doi.org/10.1038/s41598-018-23357-8,PMC5882653,29615747,CC BY,"Ebolaviruses comprises 5 species that exert varying degrees of mortality/infectivity in humans with Reston ebolaviruses (REBOV) showing the lowest and Zaire ebolaviruses (ZEBOV) showing the highest. However, the molecular basis of this differential mortality/infectivity remains unclear. Here, we report that the structural features of ebolavirus envelope glycoproteins (GPs) and one of their counter receptors, macrophage galactose-type calcium-type lectin (MGL/CD301), play crucial roles in determining viral infectivity. The low infectivity of REBOV mediated by the interaction between GPs and MGL/CD301 dramatically increased when the N-terminal 18 amino acids (33rd through 50th) of GPs were replaced with that of ZEBOV. Furthermore, structural analysis of glycans of GPs revealed that N-glycans were more extended in REBOV than in ZEBOV. N-glycan extension was reversed by the replacement of aforementioned N-terminal 18 amino acid residues. Therefore, these data strongly suggest that extended N-glycans on GPs reduce MGL/CD301-mediated viral infectivity by hindering the interaction between GPs and MGL/CD301 preferentially binds O-glycans.",2018 Apr 3,"['Fujihira, Haruhiko', 'Usami, Katsuaki', 'Matsuno, Keita', 'Takeuchi, Hideyuki', 'Denda-Nagai, Kaori', 'Furukawa, Jun-ichi', 'Shinohara, Yasuro', 'Takada, Ayato', 'Kawaoka, Yoshihiro', 'Irimura, Tatsuro']",Sci Rep,,,False
11115aa43542f817d78ca0c8ec2b50e04eb7cc17,PMC,A Critical Domain of Ebolavirus Envelope Glycoprotein Determines Glycoform and Infectivity,http://dx.doi.org/10.1038/s41598-018-23357-8,PMC5882653,29615747,CC BY,"Ebolaviruses comprises 5 species that exert varying degrees of mortality/infectivity in humans with Reston ebolaviruses (REBOV) showing the lowest and Zaire ebolaviruses (ZEBOV) showing the highest. However, the molecular basis of this differential mortality/infectivity remains unclear. Here, we report that the structural features of ebolavirus envelope glycoproteins (GPs) and one of their counter receptors, macrophage galactose-type calcium-type lectin (MGL/CD301), play crucial roles in determining viral infectivity. The low infectivity of REBOV mediated by the interaction between GPs and MGL/CD301 dramatically increased when the N-terminal 18 amino acids (33rd through 50th) of GPs were replaced with that of ZEBOV. Furthermore, structural analysis of glycans of GPs revealed that N-glycans were more extended in REBOV than in ZEBOV. N-glycan extension was reversed by the replacement of aforementioned N-terminal 18 amino acid residues. Therefore, these data strongly suggest that extended N-glycans on GPs reduce MGL/CD301-mediated viral infectivity by hindering the interaction between GPs and MGL/CD301 preferentially binds O-glycans.",2018 Apr 3,"['Fujihira, Haruhiko', 'Usami, Katsuaki', 'Matsuno, Keita', 'Takeuchi, Hideyuki', 'Denda-Nagai, Kaori', 'Furukawa, Jun-ichi', 'Shinohara, Yasuro', 'Takada, Ayato', 'Kawaoka, Yoshihiro', 'Irimura, Tatsuro']",Sci Rep,,,True
4e6b644a4ef4abd5283c18ec18237ca58e0d52e3,PMC,Human Genomic Loci Important in Common Infectious Diseases: Role of High-Throughput Sequencing and Genome-Wide Association Studies,http://dx.doi.org/10.1155/2018/1875217,PMC5884297,29755620,CC BY,"HIV/AIDS, tuberculosis (TB), and malaria are 3 major global public health threats that undermine development in many resource-poor settings. Recently, the notion that positive selection during epidemics or longer periods of exposure to common infectious diseases may have had a major effect in modifying the constitution of the human genome is being interrogated at a large scale in many populations around the world. This positive selection from infectious diseases increases power to detect associations in genome-wide association studies (GWASs). High-throughput sequencing (HTS) has transformed both the management of infectious diseases and continues to enable large-scale functional characterization of host resistance/susceptibility alleles and loci; a paradigm shift from single candidate gene studies. Application of genome sequencing technologies and genomics has enabled us to interrogate the host-pathogen interface for improving human health. Human populations are constantly locked in evolutionary arms races with pathogens; therefore, identification of common infectious disease-associated genomic variants/markers is important in therapeutic, vaccine development, and screening susceptible individuals in a population. This review describes a range of host-pathogen genomic loci that have been associated with disease susceptibility and resistant patterns in the era of HTS. We further highlight potential opportunities for these genetic markers.",2018 Mar 20,"['Mboowa, Gerald', 'Sserwadda, Ivan', 'Amujal, Marion', 'Namatovu, Norah']",Can J Infect Dis Med Microbiol,,,True
ab8c1e32b66b02cd703799df3d2ee37a1cb369b7,PMC,Enhanced protection in mice induced by immunization with inactivated whole viruses compare to spike protein of middle east respiratory syndrome coronavirus,http://dx.doi.org/10.1038/s41426-018-0056-7,PMC5884803,29618723,CC BY,"The persistent public health threat of infection with Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the need for an effective and safe MERS-CoV vaccine. In this study, we prepared and vaccinated mice with either a Spike (S) protein or inactivated whole MERS-CoV (IV) with a combined adjuvant (alum+CpG) as a vaccine formulation. Similar levels of the anti-S protein IgG response and neutralizing activity were induced by both the S protein and IV vaccines. In addition, immune responses against three other structural proteins, the envelope (E), membrane (M), and nucleocapsid (N) proteins, were also detected in sera of mice that received IV. No antigen-specific T-cell immunity was detected after vaccination based on the interferon-γ ELISpot assay. Mice were transduced with Ad5-hDPP4 after the final immunization and were then challenged with MERS-CoV (1 × 10(5) plaque-forming units). Compared with the control group (adjuvant alone), mice immunized with the S protein or IV showed slightly lower pathological damage in the lung, as well as reduced antigen expression and lung virus titers. Mice that received IV formulations also showed increased protective immunity (almost no live virus was isolated from the lung). In conclusion, our data indicate that immunization with our IV formulation induced enhanced protection in mice compared to immunization with the S protein against MERS-CoV, which should be further tested in camels and clinical trials.",2018 Apr 4,"['Deng, Yao', 'Lan, Jiaming', 'Bao, Linlin', 'Huang, Baoying', 'Ye, Fei', 'Chen, Yingzhu', 'Yao, Yanfeng', 'Wang, Wenling', 'Qin, Chuan', 'Tan, Wenjie']",Emerg Microbes Infect,,,True
db4c8228189750c2de16f125ea1a96feefd63bda,PMC,"Risk Factors for Avian Influenza H9 Infection of Chickens in Live Bird Retail Stalls of Lahore District, Pakistan 2009–2010",http://dx.doi.org/10.1038/s41598-018-23895-1,PMC5884806,29618780,CC BY,"This study was conducted to identify risk factors associated with AIV infections in live bird retail stalls (LBRS) in Lahore District, Pakistan. A cross-sectional survey of LBRS was conducted from December 2009-February 2010 using two-stage cluster sampling based on probability proportional to size. A total of 280 oropharyngeal swab sample pools were collected from 1400 birds in 8 clusters and tested by qRT-PCR for the matrix (M) gene of type A influenza virus and HA gene subtypes H9, H5 and H7. Thirty-four (34) samples were positive for the M gene, of which 28 were also positive for H9. No sample was found positive for H5 or H7. Data for 36 potential risk factors, collected by questionnaire, were analyzed by survey-weighted logistic regression and prevalence odds ratios (OR) for associated risk factors were calculated. A final multivariable model identified three risk factors for H9 infection in LRBS, namely obtaining birds from mixed sources (OR 2.28, CI(95%): 1.4–3.7), keeping birds outside cages (OR 3.10, CI(95%): 1.4–7.0) and keeping chicken breeds other than broilers (OR 6.27, CI(95%): 1.7–23.2). Sourcing birds from dealers/wholesalers, keeping birds inside cages and avoiding mixing different breeds in cages could reduce the risk of H9 infections in LRBS.",2018 Apr 4,"['Chaudhry, Mamoona', 'Rashid, Hamad B.', 'Angot, Angélique', 'Thrusfield, Michael', 'Bronsvoort, Barend M. deC', 'Capua, Ilaria', 'Cattoli, Giovanni', 'Welburn, Susan C.', 'Eisler, Mark C.']",Sci Rep,,,True
405e67def78a29e92a4de5e016d0334550153142,PMC,Niclosamide Blocks Rice Leaf Blight by Inhibiting Biofilm Formation of Xanthomonas oryzae,http://dx.doi.org/10.3389/fpls.2018.00408,PMC5884940,29651297,CC BY,"Rice (Oryza sativa) is the leading source of nutrition for more than half of the world’s population, and by far it is the most important commercial food crop. But, its growth and production are significantly hampered by the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo) which causes leaf blight disease. Earlier studies have reported the antibacterial ability of FDA-approved niclosamide drug against Xoo. However, the underlying mechanism by which niclosamide blocks the growth of Xoo remained elusive. In the present study, by employing the microbiological, microscopical, molecular, bioinformatics and analytical tools we found that niclosamide can directly inhibit the growth of the Xoo by hampering the biofilm formation and the production of xanthomonadin and exopolysaccharide substances (EPS) required for relentless growth and virulence of Xoo. Interestingly, niclosamide was found to specifically suppress the growth of Xoo without affecting other bacteria like Escherichia coli. Our electron microscopic observations disclosed that niclosamide disrupts the membrane permeability of Xoo and causes the release of intracellular components. Similarly, the molecular docking analysis disclosed the molecular interaction of niclosamide with the biofilm, virulence and quorum sensing related proteins, which was further substantiated by relative gene expression analysis where niclosamide was found to significantly downregulate the expression of these key regulatory genes. In addition, considerable changes in chemical structures were detected by Fourier Transform Infrared Spectroscopy (FTIR) in response to niclosamide treatment. Overall, our findings advocate the utilization of niclosamide as a safe and potent alternative antibacterial compound to control bacterial blight disease in rice.",2018 Mar 29,"['Sahu, Sunil Kumar', 'Zheng, Ping', 'Yao, Nan']",Front Plant Sci,,,True
eb1cc7c78d58eee6f6f81092426a9a5c9aab696c,PMC,Influenza A non-H1N1 associated with acute respiratory failure and acute renal failure in a previously vaccinated cystic fibrosis patient,http://dx.doi.org/10.5935/0103-507X.20180019,PMC5885241,29742226,CC BY,"In the 2014 - 2015 season, most influenza infections were due to A (H3N2) viruses. More than two-thirds of circulating A (H3N2) viruses are antigenically and genetically different (drifted) from the A (H3N2) vaccine component of 2014 - 2015 northern and southern Hemisphere seasonal influenza vaccines. The purpose of this paper is to report a case of seasonal influenza A non-H1N1 infection that occurred in June 2015 in an adult cystic fibrosis patient with severe lung disease previously vaccinated with the anti-flu trivalent vaccine. The patient evolved to respiratory and renal failure (without rhabdomyolysis) and was placed under mechanical ventilation and hemodialysis. The clinical outcome was positive after 39 days of hospital stay. In addition, the patient was clinically stable after 18 months of follow-up. With the recent advances in critical care medicine and in cystic fibrosis treatment, survival with advanced pulmonary disease in cystic fibrosis presents new questions and potential problems, which are still being formulated.",2018 Jan-Mar,"['Penteado, Louise Piva', 'Osório, Cecília Susin', 'Balbinotto, Antônio', 'Dalcin, Paulo de Tarso Roth']",Rev Bras Ter Intensiva,,,True
26945898e55a1c496ddbbf74d0fdec3eeafef9e7,PMC,Viral and bacterial investigations on the aetiology of recurrent pig neonatal diarrhoea cases in Spain,http://dx.doi.org/10.1186/s40813-018-0083-8,PMC5885353,29632701,CC BY,"BACKGROUND: Neonatal diarrhoea represents a major disease problem in the early stages of animal production, increasing significantly pre-weaning mortality and piglets weaned below the target weight. Enteric diseases in newborn piglets are often of endemic presentation, but may also occur as outbreaks with high morbidity and mortality. The objective of this study was to assess the frequency of different pathogens involved in cases of recurrent neonatal diarrhoea in Spain. RESULTS: A total of 327 litters from 109 sow farms located in Spain with neonatal recurrent diarrhoea were sampled to establish a differential diagnosis against the main enteric pathogens in piglets. In total, 105 out of 109 (96.3%) case submissions were positive to one of the examined enteric organisms considered potentially pathogenic (Escherichia coli, Clostridium perfringens types A and C, Transmissible gastroenteritis virus [TGEV], Porcine epidemic diarrhoea virus [PEDV] or Rotavirus A [RVA]). Fifty-eight out of 109 (53.2%) submissions were positive for only one of these pathogens, 47 out of 109 (43.1%) were positive for more than one pathogen and, finally, 4 out of 109 (3.7%) were negative for all these agents. Escherichia coli strains were isolated from all submissions tested, but only 11 of them were classified into defined pathotypes. Clostridium perfringens type A was detected in 98 submissions (89.9%) and no C. perfringens type C was found. Regarding viruses, 47 (43.1%) submissions were positive for RVA, 4 (3.7%) for PEDV and none of them for TGEV. CONCLUSION: In conclusion, C. perfringens type A, E. coli and RVA were the main pathogens found in faeces of neonatal diarrheic piglets in Spain.",2018 Apr 5,"['Mesonero-Escuredo, Susana', 'Strutzberg-Minder, Katrin', 'Casanovas, Carlos', 'Segalés, Joaquim']",Porcine Health Manag,,,True
13f8fe9cd4b06843fce134699ecc8b89cf6a2353,PMC,"Uncertainty and sensitivity analysis of the basic reproduction number of diphtheria: a case study of a Rohingya refugee camp in Bangladesh, November–December 2017",http://dx.doi.org/10.7717/peerj.4583,PMC5885970,29629244,CC BY,"BACKGROUND: A Rohingya refugee camp in Cox’s Bazar, Bangladesh experienced a large-scale diphtheria epidemic in 2017. The background information of previously immune fraction among refugees cannot be explicitly estimated, and thus we conducted an uncertainty analysis of the basic reproduction number, R(0). METHODS: A renewal process model was devised to estimate the R(0) and ascertainment rate of cases, and loss of susceptible individuals was modeled as one minus the sum of initially immune fraction and the fraction naturally infected during the epidemic. To account for the uncertainty of initially immune fraction, we employed a Latin Hypercube sampling (LHS) method. RESULTS: R(0) ranged from 4.7 to 14.8 with the median estimate at 7.2. R(0) was positively correlated with ascertainment rates. Sensitivity analysis indicated that R(0) would become smaller with greater variance of the generation time. DISCUSSION: Estimated R(0) was broadly consistent with published estimate from endemic data, indicating that the vaccination coverage of 86% has to be satisfied to prevent the epidemic by means of mass vaccination. LHS was particularly useful in the setting of a refugee camp in which the background health status is poorly quantified.",2018 Apr 2,"['Matsuyama, Ryota', 'Akhmetzhanov, Andrei R.', 'Endo, Akira', 'Lee, Hyojung', 'Yamaguchi, Takayuki', 'Tsuzuki, Shinya', 'Nishiura, Hiroshi']",PeerJ,,,True
ce2184a9344e5a044a8e307ec161cfd454b258e0,PMC,Safeguarding against Ebola: Vaccines and therapeutics to be stockpiled for future outbreaks,http://dx.doi.org/10.1371/journal.pntd.0006275,PMC5886391,29621257,CC0,,2018 Apr 5,"['Espeland, Eric M.', 'Tsai, Chia-Wei', 'Larsen, Joseph', 'Disbrow, Gary L.']",PLoS Negl Trop Dis,,,True
27fb200a637c8fff339f06399be1d563e365a7a9,PMC,DIVA metabolomics: Differentiating vaccination status following viral challenge using metabolomic profiles,http://dx.doi.org/10.1371/journal.pone.0194488,PMC5886402,29621258,CC BY,"Bovine Respiratory Disease (BRD) is a major source of economic loss within the agricultural industry. Vaccination against BRD-associated viruses does not offer complete immune protection and vaccine failure animals present potential routes for disease spread. Serological differentiation of infected from vaccinated animals (DIVA) is possible using antigen-deleted vaccines, but during virus outbreaks DIVA responses are masked by wild-type virus preventing accurate serodiagnosis. Previous work by the authors has established the potential for metabolomic profiling to reveal metabolites associated with systemic immune responses to vaccination. The current study builds on this work by demonstrating for the first time the potential to use plasma metabolite profiling to differentiate between vaccinated and non-vaccinated animals following infection-challenge. Male Holstein Friesian calves were intranasally vaccinated (Pfizer RISPOVAL(®)PI3+RSV) and subsequently challenged with Bovine Parainfluenza Virus type-3 (BPI3V) via nasal inoculation. Metabolomic plasma profiling revealed that viral challenge led to a shift in acquired plasma metabolite profiles from day 2 to 20 p.i., with 26 metabolites identified whose peak intensities were significantly different following viral challenge depending on vaccination status. Elevated levels of biliverdin and bilirubin and decreased 3-indolepropionic acid in non-vaccinated animals at day 6 p.i. may be associated with increased oxidative stress and reactive oxygen scavenging at periods of peak virus titre. During latter stages of infection, increased levels of N-[(3α,5β,12α)-3,12-dihydroxy-7,24-dioxocholan-24-yl]glycine and lysophosphatidycholine and decreased enterolactone in non-vaccinated animals may reflect suppression of innate immune response mechanisms and progression to adaptive immune responses. Levels of hexahydrohippurate were also shown to be significantly elevated in non-vaccinated animals from days 6 to 20 p.i. These findings demonstrate the potential of metabolomic profiling to identify plasma markers that can be employed in disease diagnostic applications to both differentially identify infected non-vaccinated animals during disease outbreaks and provide greater information on the health status of infected animals.",2018 Apr 5,"['Gray, Darren W.', 'Welsh, Michael D.', 'Mansoor, Fawad', 'Doherty, Simon', 'Chevallier, Olivier P.', 'Elliott, Christopher T.', 'Mooney, Mark H.']",PLoS One,,,True
1850dd919f746907173816117a024c445eaf2e91,PMC,DIVA metabolomics: Differentiating vaccination status following viral challenge using metabolomic profiles,http://dx.doi.org/10.1371/journal.pone.0194488,PMC5886402,29621258,CC BY,"Bovine Respiratory Disease (BRD) is a major source of economic loss within the agricultural industry. Vaccination against BRD-associated viruses does not offer complete immune protection and vaccine failure animals present potential routes for disease spread. Serological differentiation of infected from vaccinated animals (DIVA) is possible using antigen-deleted vaccines, but during virus outbreaks DIVA responses are masked by wild-type virus preventing accurate serodiagnosis. Previous work by the authors has established the potential for metabolomic profiling to reveal metabolites associated with systemic immune responses to vaccination. The current study builds on this work by demonstrating for the first time the potential to use plasma metabolite profiling to differentiate between vaccinated and non-vaccinated animals following infection-challenge. Male Holstein Friesian calves were intranasally vaccinated (Pfizer RISPOVAL(®)PI3+RSV) and subsequently challenged with Bovine Parainfluenza Virus type-3 (BPI3V) via nasal inoculation. Metabolomic plasma profiling revealed that viral challenge led to a shift in acquired plasma metabolite profiles from day 2 to 20 p.i., with 26 metabolites identified whose peak intensities were significantly different following viral challenge depending on vaccination status. Elevated levels of biliverdin and bilirubin and decreased 3-indolepropionic acid in non-vaccinated animals at day 6 p.i. may be associated with increased oxidative stress and reactive oxygen scavenging at periods of peak virus titre. During latter stages of infection, increased levels of N-[(3α,5β,12α)-3,12-dihydroxy-7,24-dioxocholan-24-yl]glycine and lysophosphatidycholine and decreased enterolactone in non-vaccinated animals may reflect suppression of innate immune response mechanisms and progression to adaptive immune responses. Levels of hexahydrohippurate were also shown to be significantly elevated in non-vaccinated animals from days 6 to 20 p.i. These findings demonstrate the potential of metabolomic profiling to identify plasma markers that can be employed in disease diagnostic applications to both differentially identify infected non-vaccinated animals during disease outbreaks and provide greater information on the health status of infected animals.",2018 Apr 5,"['Gray, Darren W.', 'Welsh, Michael D.', 'Mansoor, Fawad', 'Doherty, Simon', 'Chevallier, Olivier P.', 'Elliott, Christopher T.', 'Mooney, Mark H.']",PLoS One,,,False
755a251f81cd7f783201439add560141833a19e1,PMC,DIVA metabolomics: Differentiating vaccination status following viral challenge using metabolomic profiles,http://dx.doi.org/10.1371/journal.pone.0194488,PMC5886402,29621258,CC BY,"Bovine Respiratory Disease (BRD) is a major source of economic loss within the agricultural industry. Vaccination against BRD-associated viruses does not offer complete immune protection and vaccine failure animals present potential routes for disease spread. Serological differentiation of infected from vaccinated animals (DIVA) is possible using antigen-deleted vaccines, but during virus outbreaks DIVA responses are masked by wild-type virus preventing accurate serodiagnosis. Previous work by the authors has established the potential for metabolomic profiling to reveal metabolites associated with systemic immune responses to vaccination. The current study builds on this work by demonstrating for the first time the potential to use plasma metabolite profiling to differentiate between vaccinated and non-vaccinated animals following infection-challenge. Male Holstein Friesian calves were intranasally vaccinated (Pfizer RISPOVAL(®)PI3+RSV) and subsequently challenged with Bovine Parainfluenza Virus type-3 (BPI3V) via nasal inoculation. Metabolomic plasma profiling revealed that viral challenge led to a shift in acquired plasma metabolite profiles from day 2 to 20 p.i., with 26 metabolites identified whose peak intensities were significantly different following viral challenge depending on vaccination status. Elevated levels of biliverdin and bilirubin and decreased 3-indolepropionic acid in non-vaccinated animals at day 6 p.i. may be associated with increased oxidative stress and reactive oxygen scavenging at periods of peak virus titre. During latter stages of infection, increased levels of N-[(3α,5β,12α)-3,12-dihydroxy-7,24-dioxocholan-24-yl]glycine and lysophosphatidycholine and decreased enterolactone in non-vaccinated animals may reflect suppression of innate immune response mechanisms and progression to adaptive immune responses. Levels of hexahydrohippurate were also shown to be significantly elevated in non-vaccinated animals from days 6 to 20 p.i. These findings demonstrate the potential of metabolomic profiling to identify plasma markers that can be employed in disease diagnostic applications to both differentially identify infected non-vaccinated animals during disease outbreaks and provide greater information on the health status of infected animals.",2018 Apr 5,"['Gray, Darren W.', 'Welsh, Michael D.', 'Mansoor, Fawad', 'Doherty, Simon', 'Chevallier, Olivier P.', 'Elliott, Christopher T.', 'Mooney, Mark H.']",PLoS One,,,False
5bcebf16d446947cecfb9000014f486963f4fff9,PMC,DIVA metabolomics: Differentiating vaccination status following viral challenge using metabolomic profiles,http://dx.doi.org/10.1371/journal.pone.0194488,PMC5886402,29621258,CC BY,"Bovine Respiratory Disease (BRD) is a major source of economic loss within the agricultural industry. Vaccination against BRD-associated viruses does not offer complete immune protection and vaccine failure animals present potential routes for disease spread. Serological differentiation of infected from vaccinated animals (DIVA) is possible using antigen-deleted vaccines, but during virus outbreaks DIVA responses are masked by wild-type virus preventing accurate serodiagnosis. Previous work by the authors has established the potential for metabolomic profiling to reveal metabolites associated with systemic immune responses to vaccination. The current study builds on this work by demonstrating for the first time the potential to use plasma metabolite profiling to differentiate between vaccinated and non-vaccinated animals following infection-challenge. Male Holstein Friesian calves were intranasally vaccinated (Pfizer RISPOVAL(®)PI3+RSV) and subsequently challenged with Bovine Parainfluenza Virus type-3 (BPI3V) via nasal inoculation. Metabolomic plasma profiling revealed that viral challenge led to a shift in acquired plasma metabolite profiles from day 2 to 20 p.i., with 26 metabolites identified whose peak intensities were significantly different following viral challenge depending on vaccination status. Elevated levels of biliverdin and bilirubin and decreased 3-indolepropionic acid in non-vaccinated animals at day 6 p.i. may be associated with increased oxidative stress and reactive oxygen scavenging at periods of peak virus titre. During latter stages of infection, increased levels of N-[(3α,5β,12α)-3,12-dihydroxy-7,24-dioxocholan-24-yl]glycine and lysophosphatidycholine and decreased enterolactone in non-vaccinated animals may reflect suppression of innate immune response mechanisms and progression to adaptive immune responses. Levels of hexahydrohippurate were also shown to be significantly elevated in non-vaccinated animals from days 6 to 20 p.i. These findings demonstrate the potential of metabolomic profiling to identify plasma markers that can be employed in disease diagnostic applications to both differentially identify infected non-vaccinated animals during disease outbreaks and provide greater information on the health status of infected animals.",2018 Apr 5,"['Gray, Darren W.', 'Welsh, Michael D.', 'Mansoor, Fawad', 'Doherty, Simon', 'Chevallier, Olivier P.', 'Elliott, Christopher T.', 'Mooney, Mark H.']",PLoS One,,,False
70e38e1509bc32a8fc8bd45abfc24e8137d67e84,PMC,DIVA metabolomics: Differentiating vaccination status following viral challenge using metabolomic profiles,http://dx.doi.org/10.1371/journal.pone.0194488,PMC5886402,29621258,CC BY,"Bovine Respiratory Disease (BRD) is a major source of economic loss within the agricultural industry. Vaccination against BRD-associated viruses does not offer complete immune protection and vaccine failure animals present potential routes for disease spread. Serological differentiation of infected from vaccinated animals (DIVA) is possible using antigen-deleted vaccines, but during virus outbreaks DIVA responses are masked by wild-type virus preventing accurate serodiagnosis. Previous work by the authors has established the potential for metabolomic profiling to reveal metabolites associated with systemic immune responses to vaccination. The current study builds on this work by demonstrating for the first time the potential to use plasma metabolite profiling to differentiate between vaccinated and non-vaccinated animals following infection-challenge. Male Holstein Friesian calves were intranasally vaccinated (Pfizer RISPOVAL(®)PI3+RSV) and subsequently challenged with Bovine Parainfluenza Virus type-3 (BPI3V) via nasal inoculation. Metabolomic plasma profiling revealed that viral challenge led to a shift in acquired plasma metabolite profiles from day 2 to 20 p.i., with 26 metabolites identified whose peak intensities were significantly different following viral challenge depending on vaccination status. Elevated levels of biliverdin and bilirubin and decreased 3-indolepropionic acid in non-vaccinated animals at day 6 p.i. may be associated with increased oxidative stress and reactive oxygen scavenging at periods of peak virus titre. During latter stages of infection, increased levels of N-[(3α,5β,12α)-3,12-dihydroxy-7,24-dioxocholan-24-yl]glycine and lysophosphatidycholine and decreased enterolactone in non-vaccinated animals may reflect suppression of innate immune response mechanisms and progression to adaptive immune responses. Levels of hexahydrohippurate were also shown to be significantly elevated in non-vaccinated animals from days 6 to 20 p.i. These findings demonstrate the potential of metabolomic profiling to identify plasma markers that can be employed in disease diagnostic applications to both differentially identify infected non-vaccinated animals during disease outbreaks and provide greater information on the health status of infected animals.",2018 Apr 5,"['Gray, Darren W.', 'Welsh, Michael D.', 'Mansoor, Fawad', 'Doherty, Simon', 'Chevallier, Olivier P.', 'Elliott, Christopher T.', 'Mooney, Mark H.']",PLoS One,,,False
ec29bbff5e2e2eeb4bdc6651a3fbb49441ab2fa0,PMC,Efficacy and synergy of live-attenuated and inactivated influenza vaccines in young chickens,http://dx.doi.org/10.1371/journal.pone.0195285,PMC5889186,29624615,CC BY,"Outbreaks of novel highly pathogenic avian influenza viruses have been reported in poultry species in the United States since 2014. These outbreaks have proven the limitations of biosecurity control programs, and new tools are needed to reinforce the current avian influenza control arsenal. Some enzootic countries have implemented inactivated influenza vaccine (IIV) in their control programs, but there are serious concerns that a long-term use of IIV without eradication may result in the selection of novel antigenically divergent strains. A broadly protective vaccine is needed, such as live-attenuated influenza vaccine (LAIV). We showed in our previous studies that pc4-LAIV (a variant that encodes a C-terminally truncated NS1 protein) can provide significant protection against heterologous challenge virus in chickens vaccinated at 2–4 weeks of age through upregulation of innate and adaptive immune responses. The current study was conducted to compare the performances of pc4-LAIV and IIV in young chickens vaccinated at 1 day of age. A single dose of pc4-LAIV was able to induce stronger innate and mucosal IgA responses and protect young immunologically immature chickens better than a single dose of IIV. Most importantly, when 1-day-old chickens were intranasally primed with pc4-LAIV and subcutaneously boosted with IIV three weeks later, they showed a rapid, robust, and highly cross-reactive serum antibody response and a high level of mucosal IgA antibody response. This vaccination regimen warrants further optimization to increase its range of protection.",2018 Apr 6,"['Jang, Hyesun', 'Elaish, Mohamed', 'KC, Mahesh', 'Abundo, Michael C.', 'Ghorbani, Amir', 'Ngunjiri, John M.', 'Lee, Chang-Won']",PLoS One,,,True
3caab8234843e6047eacf1f7d1efc1db1d40d11b,PMC,Rapid detection of three rabbit pathogens by use of the Luminex x-TAG assay,http://dx.doi.org/10.1186/s12917-018-1438-8,PMC5889542,29625588,CC BY,"BACKGROUND: Domestic rabbits especially New Zealand white rabbits play an important role in biological research. The disease surveillance and quality control are essential to guarantee the results of animal experiments performed on rabbits. Rabbit hemorrhagic disease virus, rabbit rotavirus and Sendai virus are the important pathogens that needed to be eliminated. Rapid and sensitive method focus on these three viruses should be established for routine monitoring. The Luminex x-TAG assay based on multiplex PCR and fluorescent microsphere is a fast developing technology applied in high throughput detection. Specific primers modified with oligonucleotide sequence/biotin were used to amplify target fragments. The conjugation between oligonucleotide sequence of the PCR products and the MagPlex-TAG microspheres was specific without any cross-reaction, and the hybridization products could be analyzed using the Luminex 200 analyzer instrument. Recombinant plasmids were constructed to estimate the detection limit of the viruses. Furthermore, 40 clinical samples were used to evaluate the efficiency of this multiplex PCR based Luminex x-TAG assay. RESULTS: According to the results, this new method showed high specificity and good stability. Assessed by the recombinant plasmids, the detection limit of three viruses was 100copies/μl. Among 40 clinical specimens, 18 specimens were found positive, which was completely concordant with the conventional PCR method. CONCLUSIONS: The new developed Luminex x-TAG assay is an accurate, high throughput method for rapid detection of three important viruses of rabbits.",2018 Apr 7,"['Wu, Miaoli', 'Zhu, Yujun', 'Cong, Feng', 'Rao, Dan', 'Yuan, Wen', 'Wang, Jing', 'Huang, Bihong', 'Lian, Yuexiao', 'Zhang, Yu', 'Huang, Ren', 'Guo, Pengju']",BMC Vet Res,,,True
7d58d5cf2ba4d6f7b69784789985b0253f72685b,PMC,Performance of the TB-LAMP diagnostic assay in reference laboratories: Results from a multicentre study,http://dx.doi.org/10.1016/j.ijid.2018.01.005,PMC5890091,29410366,CC BY,"OBJECTIVE: To evaluate the diagnostic performance of TB-LAMP, a manual molecular tuberculosis (TB) detection method, and provide comparison to the Xpert MTB/RIF assay. METHODS: In a large multicentre study, two sputum samples were collected from participants with TB symptoms in reference laboratories in Peru, South Africa, Brazil, and Vietnam. Each sample was tested with TB-LAMP. The reference standard consisted of four direct smears, four cultures, and clinical and radiological findings. Individuals negative on conventional tests were followed up after 8 weeks. The Xpert MTB/RIF assay was performed on fresh or frozen samples as a molecular test comparison. RESULTS: A total of 1036 adults with suspected TB were enrolled. Among 375 culture-confirmed TB cases with 750 sputum samples, TB-LAMP detected 75.6% (95% confidence interval (CI) 71.8–79.4%), including 97.9% (95% CI 96.4–99.4%) of smear-positive TB samples and 46.6% (95% CI 40.6–52.7%) of smear-negative TB samples. Specificity in 477 culture-negative participants not treated for TB (954 sputum samples) was 98.7% (95% CI 97.9–99.6%). TB-LAMP test results were indeterminate in 0.3% of cases. CONCLUSIONS: TB-LAMP detects nearly all smear-positive and half of smear-negative TB cases and has a high specificity when performed in reference laboratories. Performance was similar to the Xpert MTB/RIF assay.",2018 Mar,"['Pham, Thu Hang', 'Peter, Jonathan', 'Mello, Fernanda C.Q.', 'Parraga, Tommy', 'Lan, Nguyen Thi Ngoc', 'Nabeta, Pamela', 'Valli, Eloise', 'Caceres, Tatiana', 'Dheda, Keertan', 'Dorman, Susan E.', 'Hillemann, Doris', 'Gray, Christen M.', 'Perkins, Mark D.']",Int J Infect Dis,,,False
c21f187377f454dff39c726a947077a5c74ae016,PMC,Identification of G-quadruplex forming sequences in three manatee papillomaviruses,http://dx.doi.org/10.1371/journal.pone.0195625,PMC5891072,29630682,CC BY,"The Florida manatee (Trichechus manatus latirotris) is a threatened aquatic mammal in United States coastal waters. Over the past decade, the appearance of papillomavirus-induced lesions and viral papillomatosis in manatees has been a concern for those involved in the management and rehabilitation of this species. To date, three manatee papillomaviruses (TmPVs) have been identified in Florida manatees, one forming cutaneous lesions (TmPV1) and two forming genital lesions (TmPV3 and TmPV4). We identified DNA sequences with the potential to form G-quadruplex structures (G4) across the three genomes. G4 were located on both DNA strands and across coding and non-coding regions on all TmPVs, offering multiple targets for viral control. Although G4 have been identified in several viral genomes, including human PVs, most research has focused on canonical structures comprised of three G-tetrads. In contrast, the vast majority of sequences we identified would allow the formation of non-canonical structures with only two G-tetrads. Our biophysical analysis confirmed the formation of G4 with parallel topology in three such sequences from the E2 region. Two of the structures appear comprised of multiple stacked two G-tetrad structures, perhaps serving to increase structural stability. Computational analysis demonstrated enrichment of G4 sequences on all TmPVs on the reverse strand in the E2/E4 region and on both strands in the L2 region. Several G4 sequences occurred at similar regional locations on all PVs, most notably on the reverse strand in the E2 region. In other cases, G4 were identified at similar regional locations only on PVs forming genital lesions. On all TmPVs, G4 sequences were located in the non-coding region near putative E2 binding sites. Together, these findings suggest that G4 are possible regulatory elements in TmPVs.",2018 Apr 9,"['Zahin, Maryam', 'Dean, William L.', 'Ghim, Shin-je', 'Joh, Joongho', 'Gray, Robert D.', 'Khanal, Sujita', 'Bossart, Gregory D.', 'Mignucci-Giannoni, Antonio A.', 'Rouchka, Eric C.', 'Jenson, Alfred B.', 'Trent, John O.', 'Chaires, Jonathan B.', 'Chariker, Julia H.']",PLoS One,,,True
690c155ad9b7ccd0b5565608b7c8c17f16aad586,PMC,Identification of G-quadruplex forming sequences in three manatee papillomaviruses,http://dx.doi.org/10.1371/journal.pone.0195625,PMC5891072,29630682,CC BY,"The Florida manatee (Trichechus manatus latirotris) is a threatened aquatic mammal in United States coastal waters. Over the past decade, the appearance of papillomavirus-induced lesions and viral papillomatosis in manatees has been a concern for those involved in the management and rehabilitation of this species. To date, three manatee papillomaviruses (TmPVs) have been identified in Florida manatees, one forming cutaneous lesions (TmPV1) and two forming genital lesions (TmPV3 and TmPV4). We identified DNA sequences with the potential to form G-quadruplex structures (G4) across the three genomes. G4 were located on both DNA strands and across coding and non-coding regions on all TmPVs, offering multiple targets for viral control. Although G4 have been identified in several viral genomes, including human PVs, most research has focused on canonical structures comprised of three G-tetrads. In contrast, the vast majority of sequences we identified would allow the formation of non-canonical structures with only two G-tetrads. Our biophysical analysis confirmed the formation of G4 with parallel topology in three such sequences from the E2 region. Two of the structures appear comprised of multiple stacked two G-tetrad structures, perhaps serving to increase structural stability. Computational analysis demonstrated enrichment of G4 sequences on all TmPVs on the reverse strand in the E2/E4 region and on both strands in the L2 region. Several G4 sequences occurred at similar regional locations on all PVs, most notably on the reverse strand in the E2 region. In other cases, G4 were identified at similar regional locations only on PVs forming genital lesions. On all TmPVs, G4 sequences were located in the non-coding region near putative E2 binding sites. Together, these findings suggest that G4 are possible regulatory elements in TmPVs.",2018 Apr 9,"['Zahin, Maryam', 'Dean, William L.', 'Ghim, Shin-je', 'Joh, Joongho', 'Gray, Robert D.', 'Khanal, Sujita', 'Bossart, Gregory D.', 'Mignucci-Giannoni, Antonio A.', 'Rouchka, Eric C.', 'Jenson, Alfred B.', 'Trent, John O.', 'Chaires, Jonathan B.', 'Chariker, Julia H.']",PLoS One,,,False
65b0605a858fcaeeb750049429e0586f2280fc14,PMC,Identification of G-quadruplex forming sequences in three manatee papillomaviruses,http://dx.doi.org/10.1371/journal.pone.0195625,PMC5891072,29630682,CC BY,"The Florida manatee (Trichechus manatus latirotris) is a threatened aquatic mammal in United States coastal waters. Over the past decade, the appearance of papillomavirus-induced lesions and viral papillomatosis in manatees has been a concern for those involved in the management and rehabilitation of this species. To date, three manatee papillomaviruses (TmPVs) have been identified in Florida manatees, one forming cutaneous lesions (TmPV1) and two forming genital lesions (TmPV3 and TmPV4). We identified DNA sequences with the potential to form G-quadruplex structures (G4) across the three genomes. G4 were located on both DNA strands and across coding and non-coding regions on all TmPVs, offering multiple targets for viral control. Although G4 have been identified in several viral genomes, including human PVs, most research has focused on canonical structures comprised of three G-tetrads. In contrast, the vast majority of sequences we identified would allow the formation of non-canonical structures with only two G-tetrads. Our biophysical analysis confirmed the formation of G4 with parallel topology in three such sequences from the E2 region. Two of the structures appear comprised of multiple stacked two G-tetrad structures, perhaps serving to increase structural stability. Computational analysis demonstrated enrichment of G4 sequences on all TmPVs on the reverse strand in the E2/E4 region and on both strands in the L2 region. Several G4 sequences occurred at similar regional locations on all PVs, most notably on the reverse strand in the E2 region. In other cases, G4 were identified at similar regional locations only on PVs forming genital lesions. On all TmPVs, G4 sequences were located in the non-coding region near putative E2 binding sites. Together, these findings suggest that G4 are possible regulatory elements in TmPVs.",2018 Apr 9,"['Zahin, Maryam', 'Dean, William L.', 'Ghim, Shin-je', 'Joh, Joongho', 'Gray, Robert D.', 'Khanal, Sujita', 'Bossart, Gregory D.', 'Mignucci-Giannoni, Antonio A.', 'Rouchka, Eric C.', 'Jenson, Alfred B.', 'Trent, John O.', 'Chaires, Jonathan B.', 'Chariker, Julia H.']",PLoS One,,,False
ed200d938907bd2820e59eabe69c8ddde54d9e52,PMC,Identification of G-quadruplex forming sequences in three manatee papillomaviruses,http://dx.doi.org/10.1371/journal.pone.0195625,PMC5891072,29630682,CC BY,"The Florida manatee (Trichechus manatus latirotris) is a threatened aquatic mammal in United States coastal waters. Over the past decade, the appearance of papillomavirus-induced lesions and viral papillomatosis in manatees has been a concern for those involved in the management and rehabilitation of this species. To date, three manatee papillomaviruses (TmPVs) have been identified in Florida manatees, one forming cutaneous lesions (TmPV1) and two forming genital lesions (TmPV3 and TmPV4). We identified DNA sequences with the potential to form G-quadruplex structures (G4) across the three genomes. G4 were located on both DNA strands and across coding and non-coding regions on all TmPVs, offering multiple targets for viral control. Although G4 have been identified in several viral genomes, including human PVs, most research has focused on canonical structures comprised of three G-tetrads. In contrast, the vast majority of sequences we identified would allow the formation of non-canonical structures with only two G-tetrads. Our biophysical analysis confirmed the formation of G4 with parallel topology in three such sequences from the E2 region. Two of the structures appear comprised of multiple stacked two G-tetrad structures, perhaps serving to increase structural stability. Computational analysis demonstrated enrichment of G4 sequences on all TmPVs on the reverse strand in the E2/E4 region and on both strands in the L2 region. Several G4 sequences occurred at similar regional locations on all PVs, most notably on the reverse strand in the E2 region. In other cases, G4 were identified at similar regional locations only on PVs forming genital lesions. On all TmPVs, G4 sequences were located in the non-coding region near putative E2 binding sites. Together, these findings suggest that G4 are possible regulatory elements in TmPVs.",2018 Apr 9,"['Zahin, Maryam', 'Dean, William L.', 'Ghim, Shin-je', 'Joh, Joongho', 'Gray, Robert D.', 'Khanal, Sujita', 'Bossart, Gregory D.', 'Mignucci-Giannoni, Antonio A.', 'Rouchka, Eric C.', 'Jenson, Alfred B.', 'Trent, John O.', 'Chaires, Jonathan B.', 'Chariker, Julia H.']",PLoS One,,,False
8b0de00e0c85c3c345cef19df1a60bff64a7e32b,PMC,Identification of G-quadruplex forming sequences in three manatee papillomaviruses,http://dx.doi.org/10.1371/journal.pone.0195625,PMC5891072,29630682,CC BY,"The Florida manatee (Trichechus manatus latirotris) is a threatened aquatic mammal in United States coastal waters. Over the past decade, the appearance of papillomavirus-induced lesions and viral papillomatosis in manatees has been a concern for those involved in the management and rehabilitation of this species. To date, three manatee papillomaviruses (TmPVs) have been identified in Florida manatees, one forming cutaneous lesions (TmPV1) and two forming genital lesions (TmPV3 and TmPV4). We identified DNA sequences with the potential to form G-quadruplex structures (G4) across the three genomes. G4 were located on both DNA strands and across coding and non-coding regions on all TmPVs, offering multiple targets for viral control. Although G4 have been identified in several viral genomes, including human PVs, most research has focused on canonical structures comprised of three G-tetrads. In contrast, the vast majority of sequences we identified would allow the formation of non-canonical structures with only two G-tetrads. Our biophysical analysis confirmed the formation of G4 with parallel topology in three such sequences from the E2 region. Two of the structures appear comprised of multiple stacked two G-tetrad structures, perhaps serving to increase structural stability. Computational analysis demonstrated enrichment of G4 sequences on all TmPVs on the reverse strand in the E2/E4 region and on both strands in the L2 region. Several G4 sequences occurred at similar regional locations on all PVs, most notably on the reverse strand in the E2 region. In other cases, G4 were identified at similar regional locations only on PVs forming genital lesions. On all TmPVs, G4 sequences were located in the non-coding region near putative E2 binding sites. Together, these findings suggest that G4 are possible regulatory elements in TmPVs.",2018 Apr 9,"['Zahin, Maryam', 'Dean, William L.', 'Ghim, Shin-je', 'Joh, Joongho', 'Gray, Robert D.', 'Khanal, Sujita', 'Bossart, Gregory D.', 'Mignucci-Giannoni, Antonio A.', 'Rouchka, Eric C.', 'Jenson, Alfred B.', 'Trent, John O.', 'Chaires, Jonathan B.', 'Chariker, Julia H.']",PLoS One,,,False
6e9f15759d6a8a4096856e9beda11125aeffcee2,PMC,Identification of G-quadruplex forming sequences in three manatee papillomaviruses,http://dx.doi.org/10.1371/journal.pone.0195625,PMC5891072,29630682,CC BY,"The Florida manatee (Trichechus manatus latirotris) is a threatened aquatic mammal in United States coastal waters. Over the past decade, the appearance of papillomavirus-induced lesions and viral papillomatosis in manatees has been a concern for those involved in the management and rehabilitation of this species. To date, three manatee papillomaviruses (TmPVs) have been identified in Florida manatees, one forming cutaneous lesions (TmPV1) and two forming genital lesions (TmPV3 and TmPV4). We identified DNA sequences with the potential to form G-quadruplex structures (G4) across the three genomes. G4 were located on both DNA strands and across coding and non-coding regions on all TmPVs, offering multiple targets for viral control. Although G4 have been identified in several viral genomes, including human PVs, most research has focused on canonical structures comprised of three G-tetrads. In contrast, the vast majority of sequences we identified would allow the formation of non-canonical structures with only two G-tetrads. Our biophysical analysis confirmed the formation of G4 with parallel topology in three such sequences from the E2 region. Two of the structures appear comprised of multiple stacked two G-tetrad structures, perhaps serving to increase structural stability. Computational analysis demonstrated enrichment of G4 sequences on all TmPVs on the reverse strand in the E2/E4 region and on both strands in the L2 region. Several G4 sequences occurred at similar regional locations on all PVs, most notably on the reverse strand in the E2 region. In other cases, G4 were identified at similar regional locations only on PVs forming genital lesions. On all TmPVs, G4 sequences were located in the non-coding region near putative E2 binding sites. Together, these findings suggest that G4 are possible regulatory elements in TmPVs.",2018 Apr 9,"['Zahin, Maryam', 'Dean, William L.', 'Ghim, Shin-je', 'Joh, Joongho', 'Gray, Robert D.', 'Khanal, Sujita', 'Bossart, Gregory D.', 'Mignucci-Giannoni, Antonio A.', 'Rouchka, Eric C.', 'Jenson, Alfred B.', 'Trent, John O.', 'Chaires, Jonathan B.', 'Chariker, Julia H.']",PLoS One,,,False
c5b5a07f30573f0149e389e071e9aef500f8f869,PMC,Identification of G-quadruplex forming sequences in three manatee papillomaviruses,http://dx.doi.org/10.1371/journal.pone.0195625,PMC5891072,29630682,CC BY,"The Florida manatee (Trichechus manatus latirotris) is a threatened aquatic mammal in United States coastal waters. Over the past decade, the appearance of papillomavirus-induced lesions and viral papillomatosis in manatees has been a concern for those involved in the management and rehabilitation of this species. To date, three manatee papillomaviruses (TmPVs) have been identified in Florida manatees, one forming cutaneous lesions (TmPV1) and two forming genital lesions (TmPV3 and TmPV4). We identified DNA sequences with the potential to form G-quadruplex structures (G4) across the three genomes. G4 were located on both DNA strands and across coding and non-coding regions on all TmPVs, offering multiple targets for viral control. Although G4 have been identified in several viral genomes, including human PVs, most research has focused on canonical structures comprised of three G-tetrads. In contrast, the vast majority of sequences we identified would allow the formation of non-canonical structures with only two G-tetrads. Our biophysical analysis confirmed the formation of G4 with parallel topology in three such sequences from the E2 region. Two of the structures appear comprised of multiple stacked two G-tetrad structures, perhaps serving to increase structural stability. Computational analysis demonstrated enrichment of G4 sequences on all TmPVs on the reverse strand in the E2/E4 region and on both strands in the L2 region. Several G4 sequences occurred at similar regional locations on all PVs, most notably on the reverse strand in the E2 region. In other cases, G4 were identified at similar regional locations only on PVs forming genital lesions. On all TmPVs, G4 sequences were located in the non-coding region near putative E2 binding sites. Together, these findings suggest that G4 are possible regulatory elements in TmPVs.",2018 Apr 9,"['Zahin, Maryam', 'Dean, William L.', 'Ghim, Shin-je', 'Joh, Joongho', 'Gray, Robert D.', 'Khanal, Sujita', 'Bossart, Gregory D.', 'Mignucci-Giannoni, Antonio A.', 'Rouchka, Eric C.', 'Jenson, Alfred B.', 'Trent, John O.', 'Chaires, Jonathan B.', 'Chariker, Julia H.']",PLoS One,,,False
302463287b1476dc97e6ec6b09dd6f4cd1b9b399,PMC,Identification of G-quadruplex forming sequences in three manatee papillomaviruses,http://dx.doi.org/10.1371/journal.pone.0195625,PMC5891072,29630682,CC BY,"The Florida manatee (Trichechus manatus latirotris) is a threatened aquatic mammal in United States coastal waters. Over the past decade, the appearance of papillomavirus-induced lesions and viral papillomatosis in manatees has been a concern for those involved in the management and rehabilitation of this species. To date, three manatee papillomaviruses (TmPVs) have been identified in Florida manatees, one forming cutaneous lesions (TmPV1) and two forming genital lesions (TmPV3 and TmPV4). We identified DNA sequences with the potential to form G-quadruplex structures (G4) across the three genomes. G4 were located on both DNA strands and across coding and non-coding regions on all TmPVs, offering multiple targets for viral control. Although G4 have been identified in several viral genomes, including human PVs, most research has focused on canonical structures comprised of three G-tetrads. In contrast, the vast majority of sequences we identified would allow the formation of non-canonical structures with only two G-tetrads. Our biophysical analysis confirmed the formation of G4 with parallel topology in three such sequences from the E2 region. Two of the structures appear comprised of multiple stacked two G-tetrad structures, perhaps serving to increase structural stability. Computational analysis demonstrated enrichment of G4 sequences on all TmPVs on the reverse strand in the E2/E4 region and on both strands in the L2 region. Several G4 sequences occurred at similar regional locations on all PVs, most notably on the reverse strand in the E2 region. In other cases, G4 were identified at similar regional locations only on PVs forming genital lesions. On all TmPVs, G4 sequences were located in the non-coding region near putative E2 binding sites. Together, these findings suggest that G4 are possible regulatory elements in TmPVs.",2018 Apr 9,"['Zahin, Maryam', 'Dean, William L.', 'Ghim, Shin-je', 'Joh, Joongho', 'Gray, Robert D.', 'Khanal, Sujita', 'Bossart, Gregory D.', 'Mignucci-Giannoni, Antonio A.', 'Rouchka, Eric C.', 'Jenson, Alfred B.', 'Trent, John O.', 'Chaires, Jonathan B.', 'Chariker, Julia H.']",PLoS One,,,False
582dfda0c1fb19ace95a5f5825a6c612f5508fd7,PMC,Identification of G-quadruplex forming sequences in three manatee papillomaviruses,http://dx.doi.org/10.1371/journal.pone.0195625,PMC5891072,29630682,CC BY,"The Florida manatee (Trichechus manatus latirotris) is a threatened aquatic mammal in United States coastal waters. Over the past decade, the appearance of papillomavirus-induced lesions and viral papillomatosis in manatees has been a concern for those involved in the management and rehabilitation of this species. To date, three manatee papillomaviruses (TmPVs) have been identified in Florida manatees, one forming cutaneous lesions (TmPV1) and two forming genital lesions (TmPV3 and TmPV4). We identified DNA sequences with the potential to form G-quadruplex structures (G4) across the three genomes. G4 were located on both DNA strands and across coding and non-coding regions on all TmPVs, offering multiple targets for viral control. Although G4 have been identified in several viral genomes, including human PVs, most research has focused on canonical structures comprised of three G-tetrads. In contrast, the vast majority of sequences we identified would allow the formation of non-canonical structures with only two G-tetrads. Our biophysical analysis confirmed the formation of G4 with parallel topology in three such sequences from the E2 region. Two of the structures appear comprised of multiple stacked two G-tetrad structures, perhaps serving to increase structural stability. Computational analysis demonstrated enrichment of G4 sequences on all TmPVs on the reverse strand in the E2/E4 region and on both strands in the L2 region. Several G4 sequences occurred at similar regional locations on all PVs, most notably on the reverse strand in the E2 region. In other cases, G4 were identified at similar regional locations only on PVs forming genital lesions. On all TmPVs, G4 sequences were located in the non-coding region near putative E2 binding sites. Together, these findings suggest that G4 are possible regulatory elements in TmPVs.",2018 Apr 9,"['Zahin, Maryam', 'Dean, William L.', 'Ghim, Shin-je', 'Joh, Joongho', 'Gray, Robert D.', 'Khanal, Sujita', 'Bossart, Gregory D.', 'Mignucci-Giannoni, Antonio A.', 'Rouchka, Eric C.', 'Jenson, Alfred B.', 'Trent, John O.', 'Chaires, Jonathan B.', 'Chariker, Julia H.']",PLoS One,,,False
1e315f235c13e3e6e7e4682c9aa2d60b48ef7d67,PMC,Identification of G-quadruplex forming sequences in three manatee papillomaviruses,http://dx.doi.org/10.1371/journal.pone.0195625,PMC5891072,29630682,CC BY,"The Florida manatee (Trichechus manatus latirotris) is a threatened aquatic mammal in United States coastal waters. Over the past decade, the appearance of papillomavirus-induced lesions and viral papillomatosis in manatees has been a concern for those involved in the management and rehabilitation of this species. To date, three manatee papillomaviruses (TmPVs) have been identified in Florida manatees, one forming cutaneous lesions (TmPV1) and two forming genital lesions (TmPV3 and TmPV4). We identified DNA sequences with the potential to form G-quadruplex structures (G4) across the three genomes. G4 were located on both DNA strands and across coding and non-coding regions on all TmPVs, offering multiple targets for viral control. Although G4 have been identified in several viral genomes, including human PVs, most research has focused on canonical structures comprised of three G-tetrads. In contrast, the vast majority of sequences we identified would allow the formation of non-canonical structures with only two G-tetrads. Our biophysical analysis confirmed the formation of G4 with parallel topology in three such sequences from the E2 region. Two of the structures appear comprised of multiple stacked two G-tetrad structures, perhaps serving to increase structural stability. Computational analysis demonstrated enrichment of G4 sequences on all TmPVs on the reverse strand in the E2/E4 region and on both strands in the L2 region. Several G4 sequences occurred at similar regional locations on all PVs, most notably on the reverse strand in the E2 region. In other cases, G4 were identified at similar regional locations only on PVs forming genital lesions. On all TmPVs, G4 sequences were located in the non-coding region near putative E2 binding sites. Together, these findings suggest that G4 are possible regulatory elements in TmPVs.",2018 Apr 9,"['Zahin, Maryam', 'Dean, William L.', 'Ghim, Shin-je', 'Joh, Joongho', 'Gray, Robert D.', 'Khanal, Sujita', 'Bossart, Gregory D.', 'Mignucci-Giannoni, Antonio A.', 'Rouchka, Eric C.', 'Jenson, Alfred B.', 'Trent, John O.', 'Chaires, Jonathan B.', 'Chariker, Julia H.']",PLoS One,,,False
0e9e17228534ee1d326415edf74216199ba43406,PMC,Identification of G-quadruplex forming sequences in three manatee papillomaviruses,http://dx.doi.org/10.1371/journal.pone.0195625,PMC5891072,29630682,CC BY,"The Florida manatee (Trichechus manatus latirotris) is a threatened aquatic mammal in United States coastal waters. Over the past decade, the appearance of papillomavirus-induced lesions and viral papillomatosis in manatees has been a concern for those involved in the management and rehabilitation of this species. To date, three manatee papillomaviruses (TmPVs) have been identified in Florida manatees, one forming cutaneous lesions (TmPV1) and two forming genital lesions (TmPV3 and TmPV4). We identified DNA sequences with the potential to form G-quadruplex structures (G4) across the three genomes. G4 were located on both DNA strands and across coding and non-coding regions on all TmPVs, offering multiple targets for viral control. Although G4 have been identified in several viral genomes, including human PVs, most research has focused on canonical structures comprised of three G-tetrads. In contrast, the vast majority of sequences we identified would allow the formation of non-canonical structures with only two G-tetrads. Our biophysical analysis confirmed the formation of G4 with parallel topology in three such sequences from the E2 region. Two of the structures appear comprised of multiple stacked two G-tetrad structures, perhaps serving to increase structural stability. Computational analysis demonstrated enrichment of G4 sequences on all TmPVs on the reverse strand in the E2/E4 region and on both strands in the L2 region. Several G4 sequences occurred at similar regional locations on all PVs, most notably on the reverse strand in the E2 region. In other cases, G4 were identified at similar regional locations only on PVs forming genital lesions. On all TmPVs, G4 sequences were located in the non-coding region near putative E2 binding sites. Together, these findings suggest that G4 are possible regulatory elements in TmPVs.",2018 Apr 9,"['Zahin, Maryam', 'Dean, William L.', 'Ghim, Shin-je', 'Joh, Joongho', 'Gray, Robert D.', 'Khanal, Sujita', 'Bossart, Gregory D.', 'Mignucci-Giannoni, Antonio A.', 'Rouchka, Eric C.', 'Jenson, Alfred B.', 'Trent, John O.', 'Chaires, Jonathan B.', 'Chariker, Julia H.']",PLoS One,,,False
1e8fd672db3be95e223c83ea48b923fadb9d5d4f,PMC,"Evaluation of the reinforced integrated disease surveillance and response strategy using short message service data transmission in two southern regions of Madagascar, 2014–15",http://dx.doi.org/10.1186/s12913-018-3081-2,PMC5891931,29631631,CC BY,"BACKGROUND: The Integrated Disease Surveillance and Response (IDSR) strategy was introduced in Madagascar in 2007. Information was collected by Healthcare structures (HS) on paper forms and transferred to the central level by post or email. Completeness of data reporting was around 20% in 2009–10. From 2011, in two southern regions data were transmitted through short messages service using one telephone provider. We evaluated the system in 2014–15 to determine its performance before changing or expanding it. METHODS: We randomly selected 80 HS and interviewed their representatives face-to-face (42) or by telephone (38). We evaluated knowledge of surveillance activities and selected case definitions, number of SMS with erroneous or missing information among the last ten transferred SMS, proportion of weekly reports received in the last 4 weeks and of the last four health alerts notified within 48 h, as well as mobile phone network coverage. RESULTS: Sixty-four percent of 80 interviewed HS representatives didn’t know their terms of reference, 83% were familiar with the malaria case definition and 32% with that of dengue. Ninety percent (37/41) of visited HS had five or more errors and 47% had missing data in the last ten SMS they transferred. The average time needed for weekly IDSR data compilation was 24 min in the Southern and 47 in the South-eastern region. Of 320 expected SMS 232 (73%) were received, 136 (43%) of them in time. Out of 38 alerts detected, four were notified on time. Nine percent (7/80) of HS had no telephone network with the current provider. CONCLUSIONS: SMS transfer has improved IDSR data completeness, but timeliness and data quality remain a problem. Healthcare staff needs training on guidelines and case definitions. From 2016, data are collected and managed electronically to reduce errors and improve the system’s performance.",2018 Apr 10,"['Randriamiarana, Rado', 'Raminosoa, Grégoire', 'Vonjitsara, Nikaria', 'Randrianasolo, Rivo', 'Rasamoelina, Harena', 'Razafimandimby, Harimahefa', 'Rakotonjanabelo, Arthur Lamina', 'Lepec, Richard', 'Flachet, Loïc', 'Halm, Ariane']",BMC Health Serv Res,,,True
e0d0ceb2658c588ef2f3549f2b9a928b441d94a6,PMC,Contribution of porcine aminopeptidase N to porcine deltacoronavirus infection,http://dx.doi.org/10.1038/s41426-018-0068-3,PMC5893578,29636467,CC BY,"Porcine deltacoronavirus (PDCoV), a member of genus Deltacoronavirus, is an emerging swine enteropathogenic coronavirus (CoV). Although outstanding efforts have led to the identification of Alphacoronavirus and Betacoronavirus receptors, the receptor for Deltacoronavirus is unclear. Here, we compared the amino acid sequences of several representative CoVs. Phylogenetic analysis showed that PDCoV spike (S) protein was close to the cluster containing transmissible gastroenteritis virus (TGEV), which utilizes porcine aminopeptidase N (pAPN) as a functional receptor. Ectopic expression of pAPN in non-susceptible BHK-21 cells rendered them susceptible to PDCoV. These results indicate that pAPN may be a functional receptor for PDCoV infection. However, treatment with APN-specific antibody and inhibitors did not completely block PDCoV infection in IPI-2I porcine intestinal epithelial cells. pAPN knockout in IPI-2I cells completely blocked TGEV infection but only slightly decreased PDCoV infection. Homologous modeling of pAPN with the S1 C-terminal domain (S1-CTD) of PDCoV or TGEV showed that TGEV S1-CTD adopted β-turns (β1–β2 and β3–β4), forming the tip of a β-barrel, to recognize pAPN. However, only the top residues in the β1–β2 turn of PDCoV S1-CTD had the possibility to support an interaction with pAPN, and the β3–β4 turn failed to contact pAPN. We also discuss the evolution and variation of PDCoV S1-CTD based on structure information, providing clues to explain the usage of pAPN by PDCoV. Taken together, the results presented herein reveal that pAPN is likely not a critical functional receptor for PDCoV, although it is involved in PDCoV infection.",2018 Apr 11,"['Zhu, Xinyu', 'Liu, Shudan', 'Wang, Xunlei', 'Luo, Zhaochen', 'Shi, Yuejun', 'Wang, Dang', 'Peng, Guiqing', 'Chen, Huanchun', 'Fang, Liurong', 'Xiao, Shaobo']",Emerg Microbes Infect,,,True
d088899449bf633659a0c6018571d0f6f7d58ec0,PMC,Enhanced Replication of Virulent Newcastle Disease Virus in Chicken Macrophages Is due to Polarized Activation of Cells by Inhibition of TLR7,http://dx.doi.org/10.3389/fimmu.2018.00366,PMC5893744,29670609,CC BY,"Newcastle disease (ND), caused by infections with virulent strains of Newcastle disease virus (NDV), is one of the most important infectious disease affecting wild, peridomestic, and domestic birds worldwide. Vaccines constructed from live, low-virulence (lentogenic) viruses are the most accepted prevention and control strategies for combating ND in poultry across the globe. Avian macrophages are one of the first cell lines of defense against microbial infection, responding to signals in the microenvironment. Although macrophages are considered to be one of the main target cells for NDV infection in vivo, very little is known about the ability of NDV to infect chicken macrophages, and virulence mechanisms of NDV as well as the polarized activation patterns of macrophages and correlation with viral infection and replication. In the present study, a cell culture model (chicken bone marrow macrophage cell line HD11) and three different virulence and genotypes of NDV (including class II virulent NA-1, class II lentogenic LaSota, and class I lentogenic F55) were used to solve the above underlying questions. Our data indicated that all three NDV strains had similar replication rates during the early stages of infection. Virulent NDV titers were shown to increase compared to the other lentogenic strains, and this growth was associated with a strong upregulation of both pro-inflammatory M1-like markers/cytokines and anti-inflammatory M2-like markers/cytokines in chicken macrophages. Virulent NDV was found to block toll-like receptor (TLR) 7 expression, inducing higher expression of type I interferons in chicken macrophages at the late stage of viral infection. Only virulent NDV replication can be inhibited by pretreatment with TLR7 ligand. Overall, this study demonstrated that virulent NDV activates a M1-/M2-like mixed polarized activation of chicken macrophages by inhibition of TLR7, resulting in enhanced replication compared to lentogenic viruses.",2018 Apr 4,"['Zhang, Pingze', 'Ding, Zhuang', 'Liu, Xinxin', 'Chen, Yanyu', 'Li, Junjiao', 'Tao, Zhi', 'Fei, Yidong', 'Xue, Cong', 'Qian, Jing', 'Wang, Xueli', 'Li, Qingmei', 'Stoeger, Tobias', 'Chen, Jianjun', 'Bi, Yuhai', 'Yin, Renfu']",Front Immunol,,,True
fa8f28950eb66ca369acb51e3cbb5b3ee178f82f,PMC,Targeting Accessories to the Crime: Nanoparticle Nucleic Acid Delivery to the Tumor Microenvironment,http://dx.doi.org/10.3389/fphar.2018.00307,PMC5893903,29670528,CC BY,"Nucleic acid delivery for cancer holds extraordinary promise. Increasing expression of tumor suppressor genes or inhibition of oncogenes in cancer cells has important therapeutic potential. However, several barriers impair progress in cancer gene delivery. These include effective delivery to cancer cells and relevant intracellular compartments. Although viral gene delivery can be effective, it has the disadvantages of being immuno-stimulatory, potentially mutagenic and lacking temporal control. Various nanoparticle (NP) platforms have been developed to overcome nucleic acid delivery hurdles, but several challenges still exist. One such challenge has been the accumulation of NPs in non-cancer cells within the tumor microenvironment (TME) as well as the circulation. While uptake by these cancer-associated cells is considered to be an off-target effect in some contexts, several strategies have now emerged to utilize NP-mediated gene delivery to intentionally alter the TME. For example, the similarity of NPs in shape and size to pathogens promotes uptake by antigen presenting cells, which can be used to increase immune stimulation and promote tumor killing by T-lymphocytes. In the era of immunotherapy, boosting the ability of the immune system to eliminate cancer cells has proven to be an exciting new area in cancer nanotechnology. Given the importance of cancer-associated cells in tumor growth and metastasis, targeting these cells in the TME opens up new therapeutic applications for NPs. This review will cover evidence for non-cancer cell accumulation of NPs in animal models and patients, summarize characteristics that promote NP delivery to different cell types, and describe several therapeutic strategies for gene modification within the TME.",2018 Apr 4,"['Harrison, Emily B.', 'Azam, Salma H.', 'Pecot, Chad V.']",Front Pharmacol,,,True
78233b5cc660bff6f716fa6cbb967775bf5c7417,PMC,Bat lung epithelial cells show greater host species-specific innate resistance than MDCK cells to human and avian influenza viruses,http://dx.doi.org/10.1186/s12985-018-0979-6,PMC5894234,29636078,CC BY,"BACKGROUND: With the recent discovery of novel H17N10 and H18N11 influenza viral RNA in bats and report on high frequency of avian H9 seroconversion in a species of free ranging bats, an important issue to address is the extent bats are susceptible to conventional avian and human influenza A viruses. METHOD: To this end, three bat species (Eidolon helvum, Carollia perspicillata and Tadarida brasiliensis) of lung epithelial cells were separately infected with two avian and two human influenza viruses to determine their relative host innate immune resistance to infection. RESULTS: All three species of bat cells were more resistant than positive control Madin-Darby canine kidney (MDCK) cells to all four influenza viruses. TB1-Lu cells lacked sialic acid α2,6-Gal receptors and were most resistant among the three bat species. Interestingly, avian viruses were relatively more replication permissive in all three bat species of cells than with the use of human viruses which suggest that bats could potentially play a role in the ecology of avian influenza viruses. Chemical inhibition of the JAK-STAT pathway in bat cells had no effect on virus production suggesting that type I interferon signalling is not a major factor in resisting influenza virus infection. CONCLUSION: Although all three species of bat cells are relatively more resistant to influenza virus infection than control MDCK cells, they are more permissive to avian than human viruses which suggest that bats could have a contributory role in the ecology of avian influenza viruses.",2018 Apr 10,"['Slater, Tessa', 'Eckerle, Isabella', 'Chang, Kin-Chow']",Virol J,,,True
a562830d55b0d773e1e687e569bf2f5af6e55f0e,PMC,Simultaneous Detection of Key Bacterial Pathogens Related to Pneumonia and Meningitis Using Multiplex PCR Coupled With Mass Spectrometry,http://dx.doi.org/10.3389/fcimb.2018.00107,PMC5895723,29675400,CC BY,"Pneumonia and meningitis continue to present an enormous public health burden and pose a major threat to young children. Among the causative organisms of pneumonia and meningitis, bacteria are the most common causes of serious disease and deaths. It is challenging to accurately and rapidly identify these agents. To solve this problem, we developed and validated a 12-plex PCR coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) method (bacterial pathogen-mass spectrometry, BP-MS) that can be used to simultaneously screen for 11 key bacterial pathogens related to pneumonia and meningitis. Forty-six nasopharyngeal swabs and 12 isolates were used to determine the specificity of the method. The results showed that, using the BP-MS method, we could accurately identify the expected bacteria without cross-reactivity with other pathogens. For the 11 target bacterial pathogens, the analytical sensitivity of the BP-MS method was as low as 10 copies/reaction. To further evaluate the clinical effectiveness of this method, 204 nasopharyngeal swabs from hospitalized children with suspected pneumonia were tested using this method. In total, 81.9% (167/204) of the samples were positive for at least one of the 11 target pathogens. Among the 167 bacteria-positive samples, the rate of multiple infections was 55.7% (93/167), and the most frequent combination was Streptococcus pneumoniae with Haemophilus influenzae, representing 46.2% (43/93) two-pathogen mixed infections. We used real-time PCR and nested PCR to confirm positive results, with identical results obtained for 81.4% (136/167) of the samples. The BP-MS method is a sensitive and specific molecular detection technique in a multiplex format and with high sample throughput. Therefore, it will be a powerful tool for pathogen screening and antibiotic selection at an early stage of disease.",2018 Apr 5,"['Zhang, Chi', 'Xiu, Leshan', 'Xiao, Yan', 'Xie, Zhengde', 'Ren, Lili', 'Peng, Junping']",Front Cell Infect Microbiol,,,True
bbbac6572458c12b598b642d848b3852f2999573,PMC,The public health emergency management system in China: trends from 2002 to 2012,http://dx.doi.org/10.1186/s12889-018-5284-1,PMC5896068,29642902,CC BY,"BACKGROUND: Public health emergencies have challenged the public health emergency management systems (PHEMSs) of many countries critically and frequently since this century. As the world’s most populated country and the second biggest economy in the world, China used to have a fragile PHEMS; however, the government took forceful actions to build PHEMS after the 2003 SARS outbreak. After more than one decade’s efforts, we tried to assess the improvements and problems of China’s PHEMS between 2002 and 2012. METHODS: We conducted two rounds of national surveys and collected the data of the year 2002 and 2012, including all 32 provincial, 139 municipal, and 489 county CDCs. The municipal and county CDCs were selected by systematic random sampling. Twenty-one indicators of four stages (preparation, readiness, response and recovery) from the National Assessment Criteria for CDC Performance were chosen to assess the ten-year trends. RESULTS: At the preparation stage, organization, mechanisms, workforce, and stockpile across all levels and regions were significantly improved after one decade’s efforts. At the readiness stage, the capability for formulating an emergency plan was also significantly improved during the same period. At the response stage, internet-based direct reporting was 98.8%, and coping scores were nearly full points of ten in 2012. At the recovery stage, the capabilities were generally lower than expected. CONCLUSIONS: Due to forceful leadership, sounder regulations, and intensive resources, China’s PHEMS has been improved at the preparation, readiness, and response stages; however, the recovery stage was still weak and could not meet the requirements of crisis management and preventive governance. In addition, CDCs in the Western region and counties lagged behind in performance on most indicators. Future priorities should include developing the recovery stage, establishing a closed feedback loop, and strengthening the capabilities of CDCs in Western region and counties.",2018 Apr 11,"['Sun, Mei', 'Xu, Ningze', 'Li, Chengyue', 'Wu, Dan', 'Zou, Jiatong', 'Wang, Ying', 'Luo, Li', 'Yu, Mingzhu', 'Zhang, Yu', 'Wang, Hua', 'Shi, Peiwu', 'Chen, Zheng', 'Wang, Jian', 'Lu, Yueliang', 'Li, Qi', 'Wang, Xinhua', 'Bi, Zhenqiang', 'Fan, Ming', 'Fu, Liping', 'Yu, Jingjin', 'Hao, Mo']",BMC Public Health,,,True
24c4787033b7069da07ce6b0b8f85f6fd5ad84b2,PMC,Comparative Epidemiology of Highly Pathogenic Avian Influenza Virus H5N1 and H5N6 in Vietnamese Live Bird Markets: Spatiotemporal Patterns of Distribution and Risk Factors,http://dx.doi.org/10.3389/fvets.2018.00051,PMC5896172,29675418,CC BY,"Highly pathogenic avian influenza (HPAI) H5N1 virus has been circulating in Vietnam since 2003, whilst outbreaks of HPAI H5N6 virus are more recent, having only been reported since 2014. Although the spatial distribution of H5N1 outbreaks and risk factors for virus occurrence has been extensively studied, there have been no comparative studies for H5N6. Data collected through active surveillance of Vietnamese live bird markets (LBMs) between 2011 and 2015 were used to explore and compare the spatiotemporal distributions of H5N1- and H5N6-positive LBMs. Conditional autoregressive models were developed to quantify spatiotemporal associations between agroecological factors and the two HPAI strains using the same set of predictor variables. Unlike H5N1, which exhibited a strong north–south divide, with repeated occurrence in the extreme south of a cluster of high-risk provinces, H5N6 was homogeneously distributed throughout Vietnam. Similarly, different agroecological factors were associated with each strain. Sample collection in the months of January and February and higher average maximum temperature were associated with higher likelihood of H5N1-positive market-day status. The likelihood of market days being positive for H5N6 increased with decreased river density, and with successive Rounds of data collection. This study highlights marked differences in spatial patterns and risk factors for H5N1 and H5N6 in Vietnam, suggesting the need for tailored surveillance and control approaches.",2018 Apr 5,"['Mellor, Kate C.', 'Meyer, Anne', 'Elkholly, Doaa A.', 'Fournié, Guillaume', 'Long, Pham T.', 'Inui, Ken', 'Padungtod, Pawin', 'Gilbert, Marius', 'Newman, Scott H.', 'Vergne, Timothée', 'Pfeiffer, Dirk U.', 'Stevens, Kim B.']",Front Vet Sci,,,True
ca68595bf945b22156e2f9b1b074973017c4cf4f,PMC,"Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability",http://dx.doi.org/10.1016/j.molcel.2018.02.023,PMC5896202,29576527,CC BY,"Deubiquitinating enzymes (DUBs) are important regulators of ubiquitin signaling. Here, we report the discovery of deubiquitinating activity in ZUFSP/C6orf113. High-resolution crystal structures of ZUFSP in complex with ubiquitin reveal several distinctive features of ubiquitin recognition and catalysis. Our analyses reveal that ZUFSP is a novel DUB with no homology to any known DUBs, leading us to classify ZUFSP as the seventh DUB family. Intriguingly, the minimal catalytic domain does not cleave polyubiquitin. We identify two ubiquitin binding domains in ZUFSP: a ZHA (ZUFSP helical arm) that binds to the distal ubiquitin and an atypical UBZ domain in ZUFSP that binds to polyubiquitin. Importantly, both domains are essential for ZUFSP to selectively cleave K63-linked polyubiquitin. We show that ZUFSP localizes to DNA lesions, where it plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage.",2018 Apr 5,"['Kwasna, Dominika', 'Abdul Rehman, Syed Arif', 'Natarajan, Jayaprakash', 'Matthews, Stephen', 'Madden, Ross', 'De Cesare, Virginia', 'Weidlich, Simone', 'Virdee, Satpal', 'Ahel, Ivan', 'Gibbs-Seymour, Ian', 'Kulathu, Yogesh']",Mol Cell,,,False
1e4ac3a8108d17c0034aa38040a99be38819c12e,PMC,"Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability",http://dx.doi.org/10.1016/j.molcel.2018.02.023,PMC5896202,29576527,CC BY,"Deubiquitinating enzymes (DUBs) are important regulators of ubiquitin signaling. Here, we report the discovery of deubiquitinating activity in ZUFSP/C6orf113. High-resolution crystal structures of ZUFSP in complex with ubiquitin reveal several distinctive features of ubiquitin recognition and catalysis. Our analyses reveal that ZUFSP is a novel DUB with no homology to any known DUBs, leading us to classify ZUFSP as the seventh DUB family. Intriguingly, the minimal catalytic domain does not cleave polyubiquitin. We identify two ubiquitin binding domains in ZUFSP: a ZHA (ZUFSP helical arm) that binds to the distal ubiquitin and an atypical UBZ domain in ZUFSP that binds to polyubiquitin. Importantly, both domains are essential for ZUFSP to selectively cleave K63-linked polyubiquitin. We show that ZUFSP localizes to DNA lesions, where it plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage.",2018 Apr 5,"['Kwasna, Dominika', 'Abdul Rehman, Syed Arif', 'Natarajan, Jayaprakash', 'Matthews, Stephen', 'Madden, Ross', 'De Cesare, Virginia', 'Weidlich, Simone', 'Virdee, Satpal', 'Ahel, Ivan', 'Gibbs-Seymour, Ian', 'Kulathu, Yogesh']",Mol Cell,,,False
95375dac99b10d7628f9c154db3799825c2f101f,PMC,Distinct Epitopes on CD13 Mediate Opposite Consequences for Cell Adhesion,http://dx.doi.org/10.1155/2018/4093435,PMC5896358,29789790,CC BY,"CD13 is a membrane glycoprotein with aminopeptidase activity, expressed on several cell types, including myeloid cells (dendritic cells, monocytes, macrophages, neutrophils, etc.). CD13 participates in several functions such as proteolytic regulation of bioactive peptides, viral receptor, angiogenesis, and tumor metastasis. CD13 has also been proposed to participate in cell adhesion, as crosslinking of CD13 by certain CD13-specific antibodies induces homotypic aggregation of monocytes and heterotypic adhesion of monocytes to endothelial cells. We generated two monoclonal antibodies (mAbs C and E) that block homotypic aggregation of U-937 monocytic cells induced by CD13-specific mAb 452. Moreover, the mAbs cause detachment of cells whose aggregation was induced by CD13 crosslinking. Both mAbs also inhibit heterotypic adhesion of U-937 monocytes to endothelial cells. mAbs C and E recognize membrane CD13 but bind to epitopes different from that recognized by mAb 452. Crosslinking of CD13 by mAb C or E is required to inhibit adhesion, as monovalent Fab fragments are not sufficient. Thus, C and E antibodies recognize a distinct epitope on CD13, and binding to this epitope interferes with both CD13-mediated cell adhesion and enzymatic activity. These antibodies may represent important tools to study cell-cell interactions mediated by CD13 in physiological and pathological conditions.",2018 Mar 29,"['Garay-Canales, Claudia A.', 'Licona-Limón, Ileana', 'Ortega, Enrique']",Biomed Res Int,,,True
7c6c25dd6ccfcf04a3c49ab5718f07991fa0b96d,PMC,Modulating Metabolism to Improve Cancer-Induced Muscle Wasting,http://dx.doi.org/10.1155/2018/7153610,PMC5896402,29785246,CC BY,"Muscle wasting is one of the main features of cancer cachexia, a multifactorial syndrome frequently occurring in oncologic patients. The onset of cachexia is associated with reduced tolerance and response to antineoplastic treatments, eventually leading to clinical conditions that are not compatible with survival. Among the mechanisms underlying cachexia, protein and energy dysmetabolism play a major role. In this regard, several potential treatments have been proposed, mainly on the basis of promising results obtained in preclinical models. However, at present, no treatment yet reached validation to be used in the clinical practice, although several drugs are currently tested in clinical trials for their ability to improve muscle metabolism in cancer patients. Along this line, the results obtained in both experimental and clinical studies clearly show that cachexia can be effectively approached by a multidirectional strategy targeting nutrition, inflammation, catabolism, and inactivity at the same time. In the present study, approaches aimed to modulate muscle metabolism in cachexia will be reviewed.",2018 Jan 29,"['Penna, Fabio', 'Ballarò, Riccardo', 'Beltrá, Marc', 'De Lucia, Serena', 'Costelli, Paola']",Oxid Med Cell Longev,,,True
033b167546d99b583a32a437dc71c73bdad6e83d,PMC,Host shifts result in parallel genetic changes when viruses evolve in closely related species,http://dx.doi.org/10.1371/journal.ppat.1006951,PMC5897010,29649296,CC BY,"Host shifts, where a pathogen invades and establishes in a new host species, are a major source of emerging infectious diseases. They frequently occur between related host species and often rely on the pathogen evolving adaptations that increase their fitness in the novel host species. To investigate genetic changes in novel hosts, we experimentally evolved replicate lineages of an RNA virus (Drosophila C Virus) in 19 different species of Drosophilidae and deep sequenced the viral genomes. We found a strong pattern of parallel evolution, where viral lineages from the same host were genetically more similar to each other than to lineages from other host species. When we compared viruses that had evolved in different host species, we found that parallel genetic changes were more likely to occur if the two host species were closely related. This suggests that when a virus adapts to one host it might also become better adapted to closely related host species. This may explain in part why host shifts tend to occur between related species, and may mean that when a new pathogen appears in a given species, closely related species may become vulnerable to the new disease.",2018 Apr 12,"['Longdon, Ben', 'Day, Jonathan P.', 'Alves, Joel M.', 'Smith, Sophia C. L.', 'Houslay, Thomas M.', 'McGonigle, John E.', 'Tagliaferri, Lucia', 'Jiggins, Francis M.']",PLoS Pathog,,,True
15be11732e317af7fa6c86abea963f89af68cc36,PMC,Host shifts result in parallel genetic changes when viruses evolve in closely related species,http://dx.doi.org/10.1371/journal.ppat.1006951,PMC5897010,29649296,CC BY,"Host shifts, where a pathogen invades and establishes in a new host species, are a major source of emerging infectious diseases. They frequently occur between related host species and often rely on the pathogen evolving adaptations that increase their fitness in the novel host species. To investigate genetic changes in novel hosts, we experimentally evolved replicate lineages of an RNA virus (Drosophila C Virus) in 19 different species of Drosophilidae and deep sequenced the viral genomes. We found a strong pattern of parallel evolution, where viral lineages from the same host were genetically more similar to each other than to lineages from other host species. When we compared viruses that had evolved in different host species, we found that parallel genetic changes were more likely to occur if the two host species were closely related. This suggests that when a virus adapts to one host it might also become better adapted to closely related host species. This may explain in part why host shifts tend to occur between related species, and may mean that when a new pathogen appears in a given species, closely related species may become vulnerable to the new disease.",2018 Apr 12,"['Longdon, Ben', 'Day, Jonathan P.', 'Alves, Joel M.', 'Smith, Sophia C. L.', 'Houslay, Thomas M.', 'McGonigle, John E.', 'Tagliaferri, Lucia', 'Jiggins, Francis M.']",PLoS Pathog,,,True
083d4f33c62061390ac7dafcc4e9a4e44518df3f,PMC,Isolation and characterization of a multifunctional flavonoid glycosyltransferase from Ornithogalum caudatum with glycosidase activity,http://dx.doi.org/10.1038/s41598-018-24277-3,PMC5897352,29651040,CC BY,"Glycosyltransferases (GTs) are bidirectional biocatalysts catalyzing the glycosylation of diverse molecules. However, the extensive applications of GTs in glycosides formation are limited due to their requirements of expensive nucleotide diphosphate (NDP)-sugars or NDP as the substrates. Here, in an effort to characterize flexible GTs for glycodiversification of natural products, we isolated a cDNA, designated as OcUGT1 from Ornithogalum caudatum, which encoded a flavonoid GT that was able to catalyze the trans-glycosylation reactions, allowing the formation of glycosides without the additions of NDP-sugars or NDP. In addition, OcUGT1 was observed to exhibit additional five types of functions, including classical sugar transfer reaction and three reversible reactions namely NDP-sugar synthesis, sugars exchange and aglycons exchange reactions, as well as enzymatic hydrolysis reaction, suggesting OcUGT1 displays both glycosyltransferase and glycosidase activities. Expression profiles revealed that the expression of OcUGT1 was development-dependent and affected by environmental factors. The unusual multifunctionality of OcUGT1 broadens the applicability of OcUGT1, thereby generating diverse carbohydrate-containing structures.",2018 Apr 12,"['Yuan, Shuai', 'Yin, Sen', 'Liu, Ming', 'Kong, Jian-Qiang']",Sci Rep,,,True
883d9e249c839788d9c21c7da412175a1314c7c7,PMC,Isolation and characterization of a multifunctional flavonoid glycosyltransferase from Ornithogalum caudatum with glycosidase activity,http://dx.doi.org/10.1038/s41598-018-24277-3,PMC5897352,29651040,CC BY,"Glycosyltransferases (GTs) are bidirectional biocatalysts catalyzing the glycosylation of diverse molecules. However, the extensive applications of GTs in glycosides formation are limited due to their requirements of expensive nucleotide diphosphate (NDP)-sugars or NDP as the substrates. Here, in an effort to characterize flexible GTs for glycodiversification of natural products, we isolated a cDNA, designated as OcUGT1 from Ornithogalum caudatum, which encoded a flavonoid GT that was able to catalyze the trans-glycosylation reactions, allowing the formation of glycosides without the additions of NDP-sugars or NDP. In addition, OcUGT1 was observed to exhibit additional five types of functions, including classical sugar transfer reaction and three reversible reactions namely NDP-sugar synthesis, sugars exchange and aglycons exchange reactions, as well as enzymatic hydrolysis reaction, suggesting OcUGT1 displays both glycosyltransferase and glycosidase activities. Expression profiles revealed that the expression of OcUGT1 was development-dependent and affected by environmental factors. The unusual multifunctionality of OcUGT1 broadens the applicability of OcUGT1, thereby generating diverse carbohydrate-containing structures.",2018 Apr 12,"['Yuan, Shuai', 'Yin, Sen', 'Liu, Ming', 'Kong, Jian-Qiang']",Sci Rep,,,True
93b0077bb11f6325fe62ea73f92250f3585872c1,PMC,Enterovirus serotypes in patients with central nervous system and respiratory infections in Viet Nam 1997–2010,http://dx.doi.org/10.1186/s12985-018-0980-0,PMC5897964,29650033,CC BY,"BACKGROUND: Enteroviruses are the most common causative agents of human illness. Enteroviruses have been associated with regional and global epidemics, recently, including with severe disease (Enterovirus A71 and D68), and are of interest as emerging viruses. Here, we typed Enterovirus A-D (EV) from central nervous system (CNS) and respiratory infections in Viet Nam. METHODS: Data and specimens from prospective observational clinical studies conducted between 1997 and 2010 were used. Species and serotypes were determined using type-specific RT-PCR and viral protein 1 or 4 (VP1, VP4) sequencing. RESULTS: Samples from patients with CNS infection (51 children – 10 CSF and 41 respiratory/rectal swabs) and 28 adults (28 CSF) and respiratory infection (124 children – 124 respiratory swabs) were analysed. Twenty-six different serotypes of the four Enterovirus species (A-D) were identified, including EV-A71 and EV-D68. Enterovirus B was associated with viral meningitis in children and adults. Hand, foot and mouth disease associated Enteroviruses A (EV-A71 and Coxsackievirus [CV] A10) were detected in children with encephalitis. Diverse serotypes of all four Enterovirus species were found in respiratory samples, including 2 polio-vaccine viruses, but also 8 CV-A24 and 8 EV-D68. With the exception of EV-D68, the relevance of these viruses in respiratory infection remains unknown. CONCLUSION: We describe the diverse spectrum of enteroviruses from patients with CNS and respiratory infections in Viet Nam between 1997 and 2010. These data confirm the global circulation of Enterovirus genera and their associations and are important for clinical diagnostics, patient management, and outbreak response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-0980-0) contains supplementary material, which is available to authorized users.",2018 Apr 12,"['B’Krong, Nguyen Thi Thuy Chinh', 'Minh, Ngo Ngoc Quang', 'Qui, Phan Tu', 'Chau, Tran Thi Hong', 'Nghia, Ho Dang Trung', 'Do, Lien Anh Ha', 'Nhung, Nguyen Ngoc', 'Van Vinh Chau, Nguyen', 'Thwaites, Guy', 'Van Tan, Le', 'van Doorn, H. Rogier', 'Thanh, Tran Tan']",Virol J,,,True
e9cabdd892daccdddc682fef1749e2475a7e5fa2,PMC,"The challenge of maintaining microscopist capacity at basic levels for malaria elimination in Jiangsu Province, China",http://dx.doi.org/10.1186/s12889-018-5307-y,PMC5898017,29650008,CC BY,"BACKGROUND: Local malaria transmission has decreased rapidly since the National Malaria Elimination Action Plan was launched in China in 2010. However, imported malaria cases from Africa and Southeast Asia still occur in China due to overseas laborers. Diagnosis by microscopy is the gold standard for malaria and is used in most hospitals in China. However, the current capacity of microscopists to manage malaria cases in hospitals and public health facilities to meet the surveillance needs to eliminate and prevent the reintroduction of malaria is unknown. METHODS: Malaria diagnoses were assessed by comparing the percentage of first visit and confirmed malaria diagnoses at Centers for Disease Control and Prevention (CDCs) and hospitals. The basic personnel information for public health departments and hospitals at different levels was investigated. The skills of microscopists for blood smear preparation and slide interpretation were also examined at the county and township levels. RESULTS: Inaccurate rate with 13.49% and 7.32%, respectively, in 2013 and 2014, from 341 and 355 reported cases from sub-provincial levels in Jiangsu province. Most of the 523 malaria cases reported in Nantong Prefecture from 2000 to 2014 involved patients who first visited county CDCs seeking treatment, however, none of these cases received confirmed diagnosis of malaria in townships or villages.The staff at county CDCs and hospitals with a higher education background performed better at making and interpreting blood smears than staff from townships. CONCLUSIONS: The network for malaria elimination in an entire province has been well established. However, an insufficient capacity for malaria diagnosis was observed, especially the preparing and reading the blood smears at the township and village levels, which is a challenge to achieving and maintaining malaria elimination.",2018 Apr 12,"['Ding, Guisheng', 'Zhu, Guoding', 'Cao, Caiqun', 'Miao, Ping', 'Cao, Yuanyuan', 'Wang, Weiming', 'Gu, Yaping', 'Xu, Sui', 'Wang, Shengqiang', 'Zhou, Huayun', 'Cao, Jun']",BMC Public Health,,,True
e77ecaf61a93272555fbeed7020c8debc7e16ba1,PMC,APOBEC3-mediated restriction of RNA virus replication,http://dx.doi.org/10.1038/s41598-018-24448-2,PMC5899082,29654310,CC BY,"APOBEC3 family members are cytidine deaminases with roles in intrinsic responses to infection by retroviruses and retrotransposons, and in the control of other DNA viruses, such as herpesviruses, parvoviruses and hepatitis B virus. Although effects of APOBEC3 members on viral DNA have been demonstrated, it is not known whether they edit RNA genomes through cytidine deamination. Here, we investigated APOBEC3-mediated restriction of Coronaviridae. In experiments in vitro, three human APOBEC3 proteins (A3C, A3F and A3H) inhibited HCoV-NL63 infection and limited production of progeny virus, but did not cause hypermutation of the coronaviral genome. APOBEC3-mediated restriction was partially dependent on enzyme activity, and was reduced by the use of enzymatically inactive APOBEC3. Moreover, APOBEC3 proteins bound to the coronaviral nucleoprotein, and this interaction also affected viral replication. Although the precise molecular mechanism of deaminase-dependent inhibition of coronavirus replication remains elusive, our results further our understanding of APOBEC-mediated restriction of RNA virus infections.",2018 Apr 13,"['Milewska, Aleksandra', 'Kindler, Eveline', 'Vkovski, Philip', 'Zeglen, Slawomir', 'Ochman, Marek', 'Thiel, Volker', 'Rajfur, Zenon', 'Pyrc, Krzysztof']",Sci Rep,,,False
472008db67b7b6037de590f4f25a12425ef181ad,PMC,APOBEC3-mediated restriction of RNA virus replication,http://dx.doi.org/10.1038/s41598-018-24448-2,PMC5899082,29654310,CC BY,"APOBEC3 family members are cytidine deaminases with roles in intrinsic responses to infection by retroviruses and retrotransposons, and in the control of other DNA viruses, such as herpesviruses, parvoviruses and hepatitis B virus. Although effects of APOBEC3 members on viral DNA have been demonstrated, it is not known whether they edit RNA genomes through cytidine deamination. Here, we investigated APOBEC3-mediated restriction of Coronaviridae. In experiments in vitro, three human APOBEC3 proteins (A3C, A3F and A3H) inhibited HCoV-NL63 infection and limited production of progeny virus, but did not cause hypermutation of the coronaviral genome. APOBEC3-mediated restriction was partially dependent on enzyme activity, and was reduced by the use of enzymatically inactive APOBEC3. Moreover, APOBEC3 proteins bound to the coronaviral nucleoprotein, and this interaction also affected viral replication. Although the precise molecular mechanism of deaminase-dependent inhibition of coronavirus replication remains elusive, our results further our understanding of APOBEC-mediated restriction of RNA virus infections.",2018 Apr 13,"['Milewska, Aleksandra', 'Kindler, Eveline', 'Vkovski, Philip', 'Zeglen, Slawomir', 'Ochman, Marek', 'Thiel, Volker', 'Rajfur, Zenon', 'Pyrc, Krzysztof']",Sci Rep,,,True
07350a14be6b53bc4a971637fb478617c2110d6c,PMC,Detection and characterisation of coronaviruses in migratory and non-migratory Australian wild birds,http://dx.doi.org/10.1038/s41598-018-24407-x,PMC5899083,29654248,CC BY,"We evaluated the presence of coronaviruses by PCR in 918 Australian wild bird samples collected during 2016–17. Coronaviruses were detected in 141 samples (15.3%) from species of ducks, shorebirds and herons and from multiple sampling locations. Sequencing of selected positive samples found mainly gammacoronaviruses, but also some deltacoronaviruses. The detection rate of coronaviruses was improved by using multiple PCR assays, as no single assay could detect all coronavirus positive samples. Sequencing of the relatively conserved Orf1 PCR amplicons found that Australian duck gammacoronaviruses were similar to duck gammacoronaviruses around the world. Some sequenced shorebird gammacoronaviruses belonged to Charadriiformes lineages, but others were more closely related to duck gammacoronaviruses. Australian duck and heron deltacoronaviruses belonged to lineages with other duck and heron deltacoronaviruses, but were almost 20% different in nucleotide sequence to other deltacoronavirus sequences available. Deltacoronavirus sequences from shorebirds formed a lineage with a deltacoronavirus from a ruddy turnstone detected in the United States. Given that Australian duck gammacoronaviruses are highly similar to those found in other regions, and Australian ducks rarely come into contact with migratory Palearctic duck species, we hypothesise that migratory shorebirds are the important vector for moving wild bird coronaviruses into and out of Australia.",2018 Apr 13,"['Chamings, Anthony', 'Nelson, Tiffanie M.', 'Vibin, Jessy', 'Wille, Michelle', 'Klaassen, Marcel', 'Alexandersen, Soren']",Sci Rep,,,False
6aae752380943069e39342f1d86741124211c312,PMC,Detection and characterisation of coronaviruses in migratory and non-migratory Australian wild birds,http://dx.doi.org/10.1038/s41598-018-24407-x,PMC5899083,29654248,CC BY,"We evaluated the presence of coronaviruses by PCR in 918 Australian wild bird samples collected during 2016–17. Coronaviruses were detected in 141 samples (15.3%) from species of ducks, shorebirds and herons and from multiple sampling locations. Sequencing of selected positive samples found mainly gammacoronaviruses, but also some deltacoronaviruses. The detection rate of coronaviruses was improved by using multiple PCR assays, as no single assay could detect all coronavirus positive samples. Sequencing of the relatively conserved Orf1 PCR amplicons found that Australian duck gammacoronaviruses were similar to duck gammacoronaviruses around the world. Some sequenced shorebird gammacoronaviruses belonged to Charadriiformes lineages, but others were more closely related to duck gammacoronaviruses. Australian duck and heron deltacoronaviruses belonged to lineages with other duck and heron deltacoronaviruses, but were almost 20% different in nucleotide sequence to other deltacoronavirus sequences available. Deltacoronavirus sequences from shorebirds formed a lineage with a deltacoronavirus from a ruddy turnstone detected in the United States. Given that Australian duck gammacoronaviruses are highly similar to those found in other regions, and Australian ducks rarely come into contact with migratory Palearctic duck species, we hypothesise that migratory shorebirds are the important vector for moving wild bird coronaviruses into and out of Australia.",2018 Apr 13,"['Chamings, Anthony', 'Nelson, Tiffanie M.', 'Vibin, Jessy', 'Wille, Michelle', 'Klaassen, Marcel', 'Alexandersen, Soren']",Sci Rep,,,True
d140ef602b48eb4187ce679fc47ec4a2d8ca248d,PMC,Bovine Nebovirus Interacts with a Wide Spectrum of Histo-Blood Group Antigens,http://dx.doi.org/10.1128/JVI.02160-17,PMC5899197,29467317,CC BY,"Some viruses within the Caliciviridae family initiate their replication cycle by attachment to cell surface carbohydrate moieties, histo-blood group antigens (HBGAs), and/or terminal sialic acids (SAs). Although bovine nebovirus (BNeV), one of the enteric caliciviruses, is an important causative agent of acute gastroenteritis in cattle, its attachment factors and possibly other cellular receptors remain unknown. Using a comprehensive series of protein-ligand biochemical assays, we sought to determine whether BNeV recognizes cell surface HBGAs and/or SAs as attachment factors. It was found that BNeV virus-like particles (VLPs) bound to A type/H type 2/Le(y) HBGAs expressed in the bovine digestive tract and are related to HBGAs expressed in humans and other host species, suggesting a wide spectrum of HBGA recognition by BNeV. BNeV VLPs also bound to a large variety of different bovine and human saliva samples of all ABH and Lewis types, supporting previously obtained results and suggesting a zoonotic potential of BNeV transmission. Removal of α1,2-linked fucose and α1,3/4-linked fucose epitopes of target HBGAs by confirmation-specific enzymes reduced the binding of BNeV VLPs to synthetic HBGAs, bovine and human saliva, cultured cell lines, and bovine small intestine mucosa, further supporting a wide HBGA binding spectrum of BNeV through recognition of α1,2-linked fucose and α1,3/4-linked fucose epitopes of targeted HBGAs. However, removal of terminal α2,3- and α2,6-linked SAs by their specific enzyme had no inhibitory effects on binding of BNeV VLPs, indicating that BNeV does not use terminal SAs as attachment factors. Further details of the binding specificity of BNeV remain to be explored. IMPORTANCE Enteric caliciviruses such as noroviruses, sapoviruses, and recoviruses are the most important etiological agents of severe acute gastroenteritis in humans and many other mammalian host species. They initiate infection by attachment to cell surface carbohydrate moieties, HBGAs, and/or terminal SAs. However, the attachment factor(s) for BNeV, a recently classified enteric calicivirus genus/type species, remains unexplored. Here, we demonstrate that BNeV VLPs have a wide spectrum of binding to synthetic HBGAs, bovine and human saliva samples, and bovine duodenal sections. We further discovered that α1,2-linked fucose and α1,3/4-linked fucose epitopes are essential for binding of BNeV VLPs. However, BNeV VLPs do not bind to terminal SAs on cell carbohydrates. Continued investigation regarding the proteinaceous receptor(s) will be necessary for better understanding of the tropism, pathogenesis, and host range of this important viral genus.",2018 Apr 13,"['Cho, Eun-Hyo', 'Soliman, Mahmoud', 'Alfajaro, Mia Madel', 'Kim, Ji-Yun', 'Seo, Ja-Young', 'Park, Jun-Gyu', 'Kim, Deok-Song', 'Baek, Yeong-Bin', 'Kang, Mun-Il', 'Park, Sang-Ik', 'Le Pendu, Jacques', 'Cho, Kyoung-Oh']",J Virol,,,True
68d01d19a8c579cd8c528e8e24cd0720216ba700,PMC,The CD8 T Cell Response to Respiratory Virus Infections,http://dx.doi.org/10.3389/fimmu.2018.00678,PMC5900024,29686673,CC BY,"Humans are highly susceptible to infection with respiratory viruses including respiratory syncytial virus (RSV), influenza virus, human metapneumovirus, rhinovirus, coronavirus, and parainfluenza virus. While some viruses simply cause symptoms of the common cold, many respiratory viruses induce severe bronchiolitis, pneumonia, and even death following infection. Despite the immense clinical burden, the majority of the most common pulmonary viruses lack long-lasting efficacious vaccines. Nearly all current vaccination strategies are designed to elicit broadly neutralizing antibodies, which prevent severe disease following a subsequent infection. However, the mucosal antibody response to many respiratory viruses is not long-lasting and declines with age. CD8 T cells are critical for mediating clearance following many acute viral infections in the lung. In addition, memory CD8 T cells are capable of providing protection against secondary infections. Therefore, the combined induction of virus-specific CD8 T cells and antibodies may provide optimal protective immunity. Herein, we review the current literature on CD8 T cell responses induced by respiratory virus infections. Additionally, we explore how this knowledge could be utilized in the development of future vaccines against respiratory viruses, with a special emphasis on RSV vaccination.",2018 Apr 9,"['Schmidt, Megan E.', 'Varga, Steven M.']",Front Immunol,,,True
70068338c7b42c6afe98139eadbf9b150a0d1af1,PMC,"A Mini Review of the Zoonotic Threat Potential of Influenza Viruses, Coronaviruses, Adenoviruses, and Enteroviruses",http://dx.doi.org/10.3389/fpubh.2018.00104,PMC5900445,29686984,CC BY,"During the last two decades, scientists have grown increasingly aware that viruses are emerging from the human–animal interface. In particular, respiratory infections are problematic; in early 2003, World Health Organization issued a worldwide alert for a previously unrecognized illness that was subsequently found to be caused by a novel coronavirus [severe acute respiratory syndrome (SARS) virus]. In addition to SARS, other respiratory pathogens have also emerged recently, contributing to the high burden of respiratory tract infection-related morbidity and mortality. Among the recently emerged respiratory pathogens are influenza viruses, coronaviruses, enteroviruses, and adenoviruses. As the genesis of these emerging viruses is not well understood and their detection normally occurs after they have crossed over and adapted to man, ideally, strategies for such novel virus detection should include intensive surveillance at the human–animal interface, particularly if one believes the paradigm that many novel emerging zoonotic viruses first circulate in animal populations and occasionally infect man before they fully adapt to man; early detection at the human–animal interface will provide earlier warning. Here, we review recent emerging virus treats for these four groups of viruses.",2018 Apr 9,"['Bailey, Emily S.', 'Fieldhouse, Jane K.', 'Choi, Jessica Y.', 'Gray, Gregory C.']",Front Public Health,,,True
6bd5e8bc7dfa11b9f9d98c97a7e7b1e8ba0e5909,PMC,Preprints in medical research: Progress and principles,http://dx.doi.org/10.1371/journal.pmed.1002563,PMC5901682,29659580,CC BY,"In this month’s editorial, the PLOS Medicine Editors discuss the role of preprints in human health research and propose a 3-part framework for ensuring benefit.",2018 Apr 16,"['Peiperl, Larry', None]",PLoS Med,,,True
3c78f14566e94220797611e80ca9136e070bbe45,PMC,"Accurate prediction of functional, structural, and stability changes in PITX2 mutations using in silico bioinformatics algorithms",http://dx.doi.org/10.1371/journal.pone.0195971,PMC5903617,29664915,CC BY,"Mutations in PITX2 have been implicated in several genetic disorders, particularly Axenfeld-Rieger syndrome. In order to determine the most reliable bioinformatics tools to assess the likely pathogenicity of PITX2 variants, the results of bioinformatics predictions were compared to the impact of variants on PITX2 structure and function. The MutPred, Provean, and PMUT bioinformatic tools were found to have the highest performance in predicting the pathogenicity effects of all 18 characterized missense variants in PITX2, all with sensitivity and specificity >93%. Applying these three programs to assess the likely pathogenicity of 13 previously uncharacterized PITX2 missense variants predicted 12/13 variants as deleterious, except A30V which was predicted as benign variant for all programs. Molecular modeling of the PITX2 homoedomain predicts that of the 31 known PITX2 variants, L54Q, F58L, V83F, V83L, W86C, W86S, and R91P alter PITX2’s structure. In contrast, the remaining 24 variants are not predicted to change PITX2’s structure. The results of molecular modeling, performed on all the PITX2 missense mutations located in the homeodomain, were compared with the findings of eight protein stability programs. CUPSAT was found to be the most reliable in predicting the effect of missense mutations on PITX2 stability. Our results showed that for PITX2, and likely other members of this homeodomain transcription factor family, MutPred, Provean, PMUT, molecular modeling, and CUPSAT can reliably be used to predict PITX2 missense variants pathogenicity.",2018 Apr 17,"['Seifi, Morteza', 'Walter, Michael A.']",PLoS One,,,True
c3bcae4e00c1244d63784b678740cfe2545a0870,PMC,"Bats, Coronaviruses, and Deforestation: Toward the Emergence of Novel Infectious Diseases?",http://dx.doi.org/10.3389/fmicb.2018.00702,PMC5904276,29696007,CC BY,,2018 Apr 11,"['Afelt, Aneta', 'Frutos, Roger', 'Devaux, Christian']",Front Microbiol,,,True
c343dec852bdfd28c3b8d0f06482408ac5ce52bd,PMC,Pathogenic Effects of IFIT2 and Interferon-β during Fatal Systemic Candida albicans Infection,http://dx.doi.org/10.1128/mBio.00365-18,PMC5904408,29666281,CC BY,"A balanced immune response to infection is essential to prevent the pathology and tissue damage that can occur from an unregulated or hyperactive host defense. Interferons (IFNs) are critical mediators of the innate defense to infection, and in this study we evaluated the contribution of a specific gene coding for IFIT2 induced by type I IFNs in a murine model of disseminated Candida albicans. Invasive candidiasis is a frequent challenge during immunosuppression or surgical medical interventions, and C. albicans is a common culprit that leads to high rates of mortality. When IFIT2 knockout mice were infected systemically with C. albicans, they were found to have improved survival and reduced fungal burden compared to wild-type mice. One of the mechanisms by which IFIT2 increases the pathological effects of invasive C. albicans appears to be suppression of NADPH oxidase activation. Loss of IFIT2 increases production of reactive oxygen species by leukocytes, and we demonstrate that IFIT2 is a binding partner of a critical regulatory subunit of NADPH oxidase, p67(phox). Since the administration of IFN has been used therapeutically to combat viral infections, cancer, and multiple sclerosis, we evaluated administration of IFN-β to mice prior to C. albicans infection. IFN-β treatment promoted pathology and death from C. albicans infection. We provide evidence that IFIT2 increases the pathological effects of invasive C. albicans and that administration of IFN-β has deleterious effects during infection.",2018 Apr 17,"['Stawowczyk, Marcin', 'Naseem, Shamoon', 'Montoya, Valeria', 'Baker, Darren P.', 'Konopka, James', 'Reich, Nancy C.']",mBio,,,True
4598b3072b36864a793b70f9f1b26b8712acc953,PMC,Pathogenic Effects of IFIT2 and Interferon-β during Fatal Systemic Candida albicans Infection,http://dx.doi.org/10.1128/mBio.00365-18,PMC5904408,29666281,CC BY,"A balanced immune response to infection is essential to prevent the pathology and tissue damage that can occur from an unregulated or hyperactive host defense. Interferons (IFNs) are critical mediators of the innate defense to infection, and in this study we evaluated the contribution of a specific gene coding for IFIT2 induced by type I IFNs in a murine model of disseminated Candida albicans. Invasive candidiasis is a frequent challenge during immunosuppression or surgical medical interventions, and C. albicans is a common culprit that leads to high rates of mortality. When IFIT2 knockout mice were infected systemically with C. albicans, they were found to have improved survival and reduced fungal burden compared to wild-type mice. One of the mechanisms by which IFIT2 increases the pathological effects of invasive C. albicans appears to be suppression of NADPH oxidase activation. Loss of IFIT2 increases production of reactive oxygen species by leukocytes, and we demonstrate that IFIT2 is a binding partner of a critical regulatory subunit of NADPH oxidase, p67(phox). Since the administration of IFN has been used therapeutically to combat viral infections, cancer, and multiple sclerosis, we evaluated administration of IFN-β to mice prior to C. albicans infection. IFN-β treatment promoted pathology and death from C. albicans infection. We provide evidence that IFIT2 increases the pathological effects of invasive C. albicans and that administration of IFN-β has deleterious effects during infection.",2018 Apr 17,"['Stawowczyk, Marcin', 'Naseem, Shamoon', 'Montoya, Valeria', 'Baker, Darren P.', 'Konopka, James', 'Reich, Nancy C.']",mBio,,,False
1b96c19d448a8ac9a4100bad68d12ce166b40869,PMC,Pathogenic Effects of IFIT2 and Interferon-β during Fatal Systemic Candida albicans Infection,http://dx.doi.org/10.1128/mBio.00365-18,PMC5904408,29666281,CC BY,"A balanced immune response to infection is essential to prevent the pathology and tissue damage that can occur from an unregulated or hyperactive host defense. Interferons (IFNs) are critical mediators of the innate defense to infection, and in this study we evaluated the contribution of a specific gene coding for IFIT2 induced by type I IFNs in a murine model of disseminated Candida albicans. Invasive candidiasis is a frequent challenge during immunosuppression or surgical medical interventions, and C. albicans is a common culprit that leads to high rates of mortality. When IFIT2 knockout mice were infected systemically with C. albicans, they were found to have improved survival and reduced fungal burden compared to wild-type mice. One of the mechanisms by which IFIT2 increases the pathological effects of invasive C. albicans appears to be suppression of NADPH oxidase activation. Loss of IFIT2 increases production of reactive oxygen species by leukocytes, and we demonstrate that IFIT2 is a binding partner of a critical regulatory subunit of NADPH oxidase, p67(phox). Since the administration of IFN has been used therapeutically to combat viral infections, cancer, and multiple sclerosis, we evaluated administration of IFN-β to mice prior to C. albicans infection. IFN-β treatment promoted pathology and death from C. albicans infection. We provide evidence that IFIT2 increases the pathological effects of invasive C. albicans and that administration of IFN-β has deleterious effects during infection.",2018 Apr 17,"['Stawowczyk, Marcin', 'Naseem, Shamoon', 'Montoya, Valeria', 'Baker, Darren P.', 'Konopka, James', 'Reich, Nancy C.']",mBio,,,False
9e73d38d2ed471855347f6e1dd6b4f3cc65c3b3d,PMC,Pathogenic Effects of IFIT2 and Interferon-β during Fatal Systemic Candida albicans Infection,http://dx.doi.org/10.1128/mBio.00365-18,PMC5904408,29666281,CC BY,"A balanced immune response to infection is essential to prevent the pathology and tissue damage that can occur from an unregulated or hyperactive host defense. Interferons (IFNs) are critical mediators of the innate defense to infection, and in this study we evaluated the contribution of a specific gene coding for IFIT2 induced by type I IFNs in a murine model of disseminated Candida albicans. Invasive candidiasis is a frequent challenge during immunosuppression or surgical medical interventions, and C. albicans is a common culprit that leads to high rates of mortality. When IFIT2 knockout mice were infected systemically with C. albicans, they were found to have improved survival and reduced fungal burden compared to wild-type mice. One of the mechanisms by which IFIT2 increases the pathological effects of invasive C. albicans appears to be suppression of NADPH oxidase activation. Loss of IFIT2 increases production of reactive oxygen species by leukocytes, and we demonstrate that IFIT2 is a binding partner of a critical regulatory subunit of NADPH oxidase, p67(phox). Since the administration of IFN has been used therapeutically to combat viral infections, cancer, and multiple sclerosis, we evaluated administration of IFN-β to mice prior to C. albicans infection. IFN-β treatment promoted pathology and death from C. albicans infection. We provide evidence that IFIT2 increases the pathological effects of invasive C. albicans and that administration of IFN-β has deleterious effects during infection.",2018 Apr 17,"['Stawowczyk, Marcin', 'Naseem, Shamoon', 'Montoya, Valeria', 'Baker, Darren P.', 'Konopka, James', 'Reich, Nancy C.']",mBio,,,False
d969316f77b5702b139d847d68e112ace0108aa4,PMC,Pathogenic Effects of IFIT2 and Interferon-β during Fatal Systemic Candida albicans Infection,http://dx.doi.org/10.1128/mBio.00365-18,PMC5904408,29666281,CC BY,"A balanced immune response to infection is essential to prevent the pathology and tissue damage that can occur from an unregulated or hyperactive host defense. Interferons (IFNs) are critical mediators of the innate defense to infection, and in this study we evaluated the contribution of a specific gene coding for IFIT2 induced by type I IFNs in a murine model of disseminated Candida albicans. Invasive candidiasis is a frequent challenge during immunosuppression or surgical medical interventions, and C. albicans is a common culprit that leads to high rates of mortality. When IFIT2 knockout mice were infected systemically with C. albicans, they were found to have improved survival and reduced fungal burden compared to wild-type mice. One of the mechanisms by which IFIT2 increases the pathological effects of invasive C. albicans appears to be suppression of NADPH oxidase activation. Loss of IFIT2 increases production of reactive oxygen species by leukocytes, and we demonstrate that IFIT2 is a binding partner of a critical regulatory subunit of NADPH oxidase, p67(phox). Since the administration of IFN has been used therapeutically to combat viral infections, cancer, and multiple sclerosis, we evaluated administration of IFN-β to mice prior to C. albicans infection. IFN-β treatment promoted pathology and death from C. albicans infection. We provide evidence that IFIT2 increases the pathological effects of invasive C. albicans and that administration of IFN-β has deleterious effects during infection.",2018 Apr 17,"['Stawowczyk, Marcin', 'Naseem, Shamoon', 'Montoya, Valeria', 'Baker, Darren P.', 'Konopka, James', 'Reich, Nancy C.']",mBio,,,False
be313fd9b4089e19250a0fbbc2012c034f706a87,PMC,Pathogenic Effects of IFIT2 and Interferon-β during Fatal Systemic Candida albicans Infection,http://dx.doi.org/10.1128/mBio.00365-18,PMC5904408,29666281,CC BY,"A balanced immune response to infection is essential to prevent the pathology and tissue damage that can occur from an unregulated or hyperactive host defense. Interferons (IFNs) are critical mediators of the innate defense to infection, and in this study we evaluated the contribution of a specific gene coding for IFIT2 induced by type I IFNs in a murine model of disseminated Candida albicans. Invasive candidiasis is a frequent challenge during immunosuppression or surgical medical interventions, and C. albicans is a common culprit that leads to high rates of mortality. When IFIT2 knockout mice were infected systemically with C. albicans, they were found to have improved survival and reduced fungal burden compared to wild-type mice. One of the mechanisms by which IFIT2 increases the pathological effects of invasive C. albicans appears to be suppression of NADPH oxidase activation. Loss of IFIT2 increases production of reactive oxygen species by leukocytes, and we demonstrate that IFIT2 is a binding partner of a critical regulatory subunit of NADPH oxidase, p67(phox). Since the administration of IFN has been used therapeutically to combat viral infections, cancer, and multiple sclerosis, we evaluated administration of IFN-β to mice prior to C. albicans infection. IFN-β treatment promoted pathology and death from C. albicans infection. We provide evidence that IFIT2 increases the pathological effects of invasive C. albicans and that administration of IFN-β has deleterious effects during infection.",2018 Apr 17,"['Stawowczyk, Marcin', 'Naseem, Shamoon', 'Montoya, Valeria', 'Baker, Darren P.', 'Konopka, James', 'Reich, Nancy C.']",mBio,,,False
723d1419c7355dbe049715238f16ee6a92cf9875,PMC,Pathogenic Effects of IFIT2 and Interferon-β during Fatal Systemic Candida albicans Infection,http://dx.doi.org/10.1128/mBio.00365-18,PMC5904408,29666281,CC BY,"A balanced immune response to infection is essential to prevent the pathology and tissue damage that can occur from an unregulated or hyperactive host defense. Interferons (IFNs) are critical mediators of the innate defense to infection, and in this study we evaluated the contribution of a specific gene coding for IFIT2 induced by type I IFNs in a murine model of disseminated Candida albicans. Invasive candidiasis is a frequent challenge during immunosuppression or surgical medical interventions, and C. albicans is a common culprit that leads to high rates of mortality. When IFIT2 knockout mice were infected systemically with C. albicans, they were found to have improved survival and reduced fungal burden compared to wild-type mice. One of the mechanisms by which IFIT2 increases the pathological effects of invasive C. albicans appears to be suppression of NADPH oxidase activation. Loss of IFIT2 increases production of reactive oxygen species by leukocytes, and we demonstrate that IFIT2 is a binding partner of a critical regulatory subunit of NADPH oxidase, p67(phox). Since the administration of IFN has been used therapeutically to combat viral infections, cancer, and multiple sclerosis, we evaluated administration of IFN-β to mice prior to C. albicans infection. IFN-β treatment promoted pathology and death from C. albicans infection. We provide evidence that IFIT2 increases the pathological effects of invasive C. albicans and that administration of IFN-β has deleterious effects during infection.",2018 Apr 17,"['Stawowczyk, Marcin', 'Naseem, Shamoon', 'Montoya, Valeria', 'Baker, Darren P.', 'Konopka, James', 'Reich, Nancy C.']",mBio,,,False
47ffae3d18605cb87ccddaed11384d3e9f83d0af,PMC,Pathogenic Effects of IFIT2 and Interferon-β during Fatal Systemic Candida albicans Infection,http://dx.doi.org/10.1128/mBio.00365-18,PMC5904408,29666281,CC BY,"A balanced immune response to infection is essential to prevent the pathology and tissue damage that can occur from an unregulated or hyperactive host defense. Interferons (IFNs) are critical mediators of the innate defense to infection, and in this study we evaluated the contribution of a specific gene coding for IFIT2 induced by type I IFNs in a murine model of disseminated Candida albicans. Invasive candidiasis is a frequent challenge during immunosuppression or surgical medical interventions, and C. albicans is a common culprit that leads to high rates of mortality. When IFIT2 knockout mice were infected systemically with C. albicans, they were found to have improved survival and reduced fungal burden compared to wild-type mice. One of the mechanisms by which IFIT2 increases the pathological effects of invasive C. albicans appears to be suppression of NADPH oxidase activation. Loss of IFIT2 increases production of reactive oxygen species by leukocytes, and we demonstrate that IFIT2 is a binding partner of a critical regulatory subunit of NADPH oxidase, p67(phox). Since the administration of IFN has been used therapeutically to combat viral infections, cancer, and multiple sclerosis, we evaluated administration of IFN-β to mice prior to C. albicans infection. IFN-β treatment promoted pathology and death from C. albicans infection. We provide evidence that IFIT2 increases the pathological effects of invasive C. albicans and that administration of IFN-β has deleterious effects during infection.",2018 Apr 17,"['Stawowczyk, Marcin', 'Naseem, Shamoon', 'Montoya, Valeria', 'Baker, Darren P.', 'Konopka, James', 'Reich, Nancy C.']",mBio,,,False
6f166253a755c2ad38aac8e51c840da528a87d18,PMC,Pathogenic Effects of IFIT2 and Interferon-β during Fatal Systemic Candida albicans Infection,http://dx.doi.org/10.1128/mBio.00365-18,PMC5904408,29666281,CC BY,"A balanced immune response to infection is essential to prevent the pathology and tissue damage that can occur from an unregulated or hyperactive host defense. Interferons (IFNs) are critical mediators of the innate defense to infection, and in this study we evaluated the contribution of a specific gene coding for IFIT2 induced by type I IFNs in a murine model of disseminated Candida albicans. Invasive candidiasis is a frequent challenge during immunosuppression or surgical medical interventions, and C. albicans is a common culprit that leads to high rates of mortality. When IFIT2 knockout mice were infected systemically with C. albicans, they were found to have improved survival and reduced fungal burden compared to wild-type mice. One of the mechanisms by which IFIT2 increases the pathological effects of invasive C. albicans appears to be suppression of NADPH oxidase activation. Loss of IFIT2 increases production of reactive oxygen species by leukocytes, and we demonstrate that IFIT2 is a binding partner of a critical regulatory subunit of NADPH oxidase, p67(phox). Since the administration of IFN has been used therapeutically to combat viral infections, cancer, and multiple sclerosis, we evaluated administration of IFN-β to mice prior to C. albicans infection. IFN-β treatment promoted pathology and death from C. albicans infection. We provide evidence that IFIT2 increases the pathological effects of invasive C. albicans and that administration of IFN-β has deleterious effects during infection.",2018 Apr 17,"['Stawowczyk, Marcin', 'Naseem, Shamoon', 'Montoya, Valeria', 'Baker, Darren P.', 'Konopka, James', 'Reich, Nancy C.']",mBio,,,False
f45cfe6b85ed56ba26e5dfafd1bdabbbe0dc75a3,PMC,Pathogenic Effects of IFIT2 and Interferon-β during Fatal Systemic Candida albicans Infection,http://dx.doi.org/10.1128/mBio.00365-18,PMC5904408,29666281,CC BY,"A balanced immune response to infection is essential to prevent the pathology and tissue damage that can occur from an unregulated or hyperactive host defense. Interferons (IFNs) are critical mediators of the innate defense to infection, and in this study we evaluated the contribution of a specific gene coding for IFIT2 induced by type I IFNs in a murine model of disseminated Candida albicans. Invasive candidiasis is a frequent challenge during immunosuppression or surgical medical interventions, and C. albicans is a common culprit that leads to high rates of mortality. When IFIT2 knockout mice were infected systemically with C. albicans, they were found to have improved survival and reduced fungal burden compared to wild-type mice. One of the mechanisms by which IFIT2 increases the pathological effects of invasive C. albicans appears to be suppression of NADPH oxidase activation. Loss of IFIT2 increases production of reactive oxygen species by leukocytes, and we demonstrate that IFIT2 is a binding partner of a critical regulatory subunit of NADPH oxidase, p67(phox). Since the administration of IFN has been used therapeutically to combat viral infections, cancer, and multiple sclerosis, we evaluated administration of IFN-β to mice prior to C. albicans infection. IFN-β treatment promoted pathology and death from C. albicans infection. We provide evidence that IFIT2 increases the pathological effects of invasive C. albicans and that administration of IFN-β has deleterious effects during infection.",2018 Apr 17,"['Stawowczyk, Marcin', 'Naseem, Shamoon', 'Montoya, Valeria', 'Baker, Darren P.', 'Konopka, James', 'Reich, Nancy C.']",mBio,,,False
f4117ab009596bf0f4ab6391615d5124125b1006,PMC,"The Origin, Dynamic Morphology, and PI4P-Independent Formation of Encephalomyocarditis Virus Replication Organelles",http://dx.doi.org/10.1128/mBio.00420-18,PMC5904412,29666283,CC BY,"Picornaviruses induce dramatic rearrangements of endomembranes in the cells that they infect to produce dedicated platforms for viral replication. These structures, termed replication organelles (ROs), have been well characterized for the Enterovirus genus of the Picornaviridae. However, it is unknown whether the diverse RO morphologies associated with enterovirus infection are conserved among other picornaviruses. Here, we use serial electron tomography at different stages of infection to assess the three-dimensional architecture of ROs induced by encephalomyocarditis virus (EMCV), a member of the Cardiovirus genus of the family of picornaviruses that is distantly related. Ultrastructural analyses revealed connections between early single-membrane EMCV ROs and the endoplasmic reticulum (ER), establishing the ER as a likely donor organelle for their formation. These early single-membrane ROs appear to transform into double-membrane vesicles (DMVs) as infection progresses. Both single- and double-membrane structures were found to support viral RNA synthesis, and progeny viruses accumulated in close proximity, suggesting a spatial association between RNA synthesis and virus assembly. Further, we explored the role of phosphatidylinositol 4-phosphate (PI4P), a critical host factor for both enterovirus and cardiovirus replication that has been recently found to expedite enterovirus RO formation rather than being strictly required. By exploiting an EMCV escape mutant, we found that low-PI4P conditions could also be overcome for the formation of cardiovirus ROs. Collectively, our data show that despite differences in the membrane source, there are striking similarities in the biogenesis, morphology, and transformation of cardiovirus and enterovirus ROs, which may well extend to other picornaviruses.",2018 Apr 17,"['Melia, C. E.', 'van der Schaar, H. M.', 'de Jong, A. W. M.', 'Lyoo, H. R.', 'Snijder, E. J.', 'Koster, A. J.', 'van Kuppeveld, F. J. M.', 'Bárcena, M.']",mBio,,,True
129341a52b43ccd59368d094950322d983ebe223,PMC,Effect of selected gastrointestinal parasites and viral agents on fecal S100A12 concentrations in puppies as a potential comparative model,http://dx.doi.org/10.1186/s13071-018-2841-5,PMC5905106,29665827,CC BY,"BACKGROUND: Previous data suggest that fecal S100A12 has clinical utility as a biomarker of chronic gastrointestinal inflammation (idiopathic inflammatory bowel disease) in both people and dogs, but the effect of gastrointestinal pathogens on fecal S100A12 concentrations is largely unknown. The role of S100A12 in parasite and viral infections is also difficult to study in traditional animal models due to the lack of S100A12 expression in rodents. Thus, the aim of this study was to evaluate fecal S100A12 concentrations in a cohort of puppies with intestinal parasites (Cystoisospora spp., Toxocara canis, Giardia sp.) and viral agents that are frequently encountered and known to cause gastrointestinal signs in dogs (coronavirus, parvovirus) as a comparative model. METHODS: Spot fecal samples were collected from 307 puppies [median age (range): 7 (4−13) weeks; 29 different breeds] in French breeding kennels, and fecal scores (semiquantitative system; scores 1−13) were assigned. Fecal samples were tested for Cystoisospora spp. (C. canis and C. ohioensis), Toxocara canis, Giardia sp., as well as canine coronavirus (CCV) and parvovirus (CPV). S100A12 concentrations were measured in all fecal samples using an in-house radioimmunoassay. Statistical analyses were performed using non-parametric 2-group or multiple-group comparisons, non-parametric correlation analysis, association testing between nominal variables, and construction of a multivariate mixed model. RESULTS: Fecal S100A12 concentrations ranged from < 24−14,363 ng/g. Univariate analysis only showed increased fecal S100A12 concentrations in dogs shedding Cystoisospora spp. (P = 0.0384) and in dogs infected with parvovirus (P = 0.0277), whereas dogs infected with coronavirus had decreased fecal S100A12 concentrations (P = 0.0345). However, shedding of any single enteropathogen did not affect fecal S100A12 concentrations in multivariate analysis (all P > 0.05) in this study. Only fecal score and breed size had an effect on fecal S100A12 concentrations in multivariate analysis (P < 0.0001). CONCLUSIONS: An infection with any single enteropathogen tested in this study is unlikely to alter fecal S100A12 concentrations, and these preliminary data are important for further studies evaluating fecal S100A12 concentrations in dogs or when using fecal S100A12 concentrations as a biomarker in patients with chronic idiopathic gastrointestinal inflammation.",2018 Apr 17,"['Heilmann, Romy M.', 'Grellet, Aurélien', 'Grützner, Niels', 'Cranford, Shannon M.', 'Suchodolski, Jan S.', 'Chastant-Maillard, Sylvie', 'Steiner, Jörg M.']",Parasit Vectors,,,True
70f2b5c592dd6da732100912bcd2ca928a882842,PMC,Contact among healthcare workers in the hospital setting: developing the evidence base for innovative approaches to infection control,http://dx.doi.org/10.1186/s12879-018-3093-x,PMC5905140,29665775,CC BY,"BACKGROUND: Nosocomial, or healthcare-associated infections (HAI), exact a high medical and financial toll on patients, healthcare workers, caretakers, and the health system. Interpersonal contact patterns play a large role in infectious disease spread, but little is known about the relationship between health care workers’ (HCW) movements and contact patterns within a heath care facility and HAI. Quantitatively capturing these patterns will aid in understanding the dynamics of HAI and may lead to more targeted and effective control strategies in the hospital setting. METHODS: Staff at 3 urban university-based tertiary care hospitals in Canada completed a detailed questionnaire on demographics, interpersonal contacts, in-hospital movement, and infection prevention and control practices. Staff were divided into categories of administrative/support, nurses, physicians, and “Other HCWs” - a fourth distinct category, which excludes physicians and nurses. Using quantitative network modeling tools, we constructed the resulting HCW “co-location network” to illustrate contacts among different occupations and with locations in hospital settings. RESULTS: Among 3048 respondents (response rate 38%) an average of 3.79, 3.69 and 3.88 floors were visited by each HCW each week in the 3 hospitals, with a standard deviation of 2.63, 1.74 and 2.08, respectively. Physicians reported the highest rate of direct patient contacts (> 20 patients/day) but the lowest rate of contacts with other HCWs; nurses had the most extended (> 20 min) periods of direct patient contact. “Other HCWs” had the most direct daily contact with all other HCWs. Physicians also reported significantly more locations visited per week than nurses, other HCW, or administrators; nurses visited the fewest. Public spaces such as the cafeteria had the most staff visits per week, but the least mean hours spent per visit. Inpatient settings had significantly more HCW interactions per week than outpatient settings. CONCLUSIONS: HCW contact patterns and spatial movement demonstrate significant heterogeneity by occupation. Control strategies that address this diversity among health care workers may be more effective than “one-strategy-fits-all” HAI prevention and control programs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3093-x) contains supplementary material, which is available to authorized users.",2018 Apr 17,"['English, Krista M.', 'Langley, Joanne M.', 'McGeer, Allison', 'Hupert, Nathaniel', 'Tellier, Raymond', 'Henry, Bonnie', 'Halperin, Scott A.', 'Johnston, Lynn', 'Pourbohloul, Babak']",BMC Infect Dis,,,False
168667e863cc79cb44157edf0e39ca66a37b2b7b,PMC,Contact among healthcare workers in the hospital setting: developing the evidence base for innovative approaches to infection control,http://dx.doi.org/10.1186/s12879-018-3093-x,PMC5905140,29665775,CC BY,"BACKGROUND: Nosocomial, or healthcare-associated infections (HAI), exact a high medical and financial toll on patients, healthcare workers, caretakers, and the health system. Interpersonal contact patterns play a large role in infectious disease spread, but little is known about the relationship between health care workers’ (HCW) movements and contact patterns within a heath care facility and HAI. Quantitatively capturing these patterns will aid in understanding the dynamics of HAI and may lead to more targeted and effective control strategies in the hospital setting. METHODS: Staff at 3 urban university-based tertiary care hospitals in Canada completed a detailed questionnaire on demographics, interpersonal contacts, in-hospital movement, and infection prevention and control practices. Staff were divided into categories of administrative/support, nurses, physicians, and “Other HCWs” - a fourth distinct category, which excludes physicians and nurses. Using quantitative network modeling tools, we constructed the resulting HCW “co-location network” to illustrate contacts among different occupations and with locations in hospital settings. RESULTS: Among 3048 respondents (response rate 38%) an average of 3.79, 3.69 and 3.88 floors were visited by each HCW each week in the 3 hospitals, with a standard deviation of 2.63, 1.74 and 2.08, respectively. Physicians reported the highest rate of direct patient contacts (> 20 patients/day) but the lowest rate of contacts with other HCWs; nurses had the most extended (> 20 min) periods of direct patient contact. “Other HCWs” had the most direct daily contact with all other HCWs. Physicians also reported significantly more locations visited per week than nurses, other HCW, or administrators; nurses visited the fewest. Public spaces such as the cafeteria had the most staff visits per week, but the least mean hours spent per visit. Inpatient settings had significantly more HCW interactions per week than outpatient settings. CONCLUSIONS: HCW contact patterns and spatial movement demonstrate significant heterogeneity by occupation. Control strategies that address this diversity among health care workers may be more effective than “one-strategy-fits-all” HAI prevention and control programs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3093-x) contains supplementary material, which is available to authorized users.",2018 Apr 17,"['English, Krista M.', 'Langley, Joanne M.', 'McGeer, Allison', 'Hupert, Nathaniel', 'Tellier, Raymond', 'Henry, Bonnie', 'Halperin, Scott A.', 'Johnston, Lynn', 'Pourbohloul, Babak']",BMC Infect Dis,,,True
1697f41650571796c51a52e8f5412d293f620c79,PMC,Comparison of Respiratory Pathogen Detection in Upper versus Lower Respiratory Tract Samples Using the BioFire FilmArray Respiratory Panel in the Immunocompromised Host,http://dx.doi.org/10.1155/2018/2685723,PMC5907482,29849830,CC BY,"BACKGROUND: The FilmArray Respiratory Panel (FARP) (BioFire Diagnostics, Inc.) is a multiplex, polymerase chain reaction (PCR) technique that can detect 17 respiratory viruses and 3 bacterial targets in a single reaction. Immunocompromised hosts (ICH) with respiratory illnesses often undergo bronchoscopy with bronchoalveolar lavage (BAL). This prospective study aimed to evaluate the yield and concordance of NP and BAL FARP testing when performed on the same patient concurrently. METHODS: From February to December 2016, 125 patients (100 ICH and 25 non-ICH) were enrolled. NP swabs and BAL samples were sent for FARP testing. RESULTS: The yield of the BAL FARP among ICH and non-ICH was 24% (24/100) and 8% (2/25), respectively. The yield of positive NP swabs in ICH was 27% (27/100) versus 4% (1/25) in non-ICH. The majority of patients (89%; 111/125) had concordant results between NP and BAL specimens. Of the 24 ICH patients who had a positive BAL FARP, the majority (79%) had the same pathogen detected from the NP swab. CONCLUSION: The FARP may be useful in the ICH. Given the high concordance, in patients whom a pathogen is identified on the NP FARP, a FARP performed on BAL will likely yield the same result. However, if the NP FARP is negative, performing the test on a BAL sample may have an incremental yield.",2018 Apr 5,"['Azadeh, Natalya', 'Sakata, Kenneth K.', 'Saeed, Ali', 'Mullon, John J.', 'Grys, Thomas E.', 'Limper, Andrew H.', 'Binnicker, Matthew J.']",Can Respir J,,,True
cff09cd72961bfaa2c50919e65b093c20937b137,PMC,Transmembrane Domains of Highly Pathogenic Viral Fusion Proteins Exhibit Trimeric Association In Vitro,http://dx.doi.org/10.1128/mSphere.00047-18,PMC5907656,29669880,CC BY,"Enveloped viruses require viral fusion proteins to promote fusion of the viral envelope with a target cell membrane. To drive fusion, these proteins undergo large conformational changes that must occur at the right place and at the right time. Understanding the elements which control the stability of the prefusion state and the initiation of conformational changes is key to understanding the function of these important proteins. The construction of mutations in the fusion protein transmembrane domains (TMDs) or the replacement of these domains with lipid anchors has implicated the TMD in the fusion process. However, the structural and molecular details of the role of the TMD in these fusion events remain unclear. Previously, we demonstrated that isolated paramyxovirus fusion protein TMDs associate in a monomer-trimer equilibrium, using sedimentation equilibrium analytical ultracentrifugation. Using a similar approach, the work presented here indicates that trimeric interactions also occur between the fusion protein TMDs of Ebola virus, influenza virus, severe acute respiratory syndrome coronavirus (SARS CoV), and rabies virus. Our results suggest that TM-TM interactions are important in the fusion protein function of diverse viral families. IMPORTANCE Many important human pathogens are enveloped viruses that utilize membrane-bound glycoproteins to mediate viral entry. Factors that contribute to the stability of these glycoproteins have been identified in the ectodomain of several viral fusion proteins, including residues within the soluble ectodomain. Although it is often thought to simply act as an anchor, the transmembrane domain of viral fusion proteins has been implicated in protein stability and function as well. Here, using a biophysical approach, we demonstrated that the fusion protein transmembrane domains of several deadly pathogens—Ebola virus, influenza virus, SARS CoV, and rabies virus—self-associate. This observation across various viral families suggests that transmembrane domain interactions may be broadly relevant and serve as a new target for therapeutic development.",2018 Apr 18,"['Webb, Stacy R.', 'Smith, Stacy E.', 'Fried, Michael G.', 'Dutch, Rebecca Ellis']",mSphere,,,True
a204aafa38365dbcc0a26af3ca2c6d3313d7fab2,PMC,"Respiratory syncytial virus evaluation among asymptomatic and symptomatic subjects in a university hospital in Sao Paulo, Brazil, in the period of 2009‐2013",http://dx.doi.org/10.1111/irv.12518,PMC5907818,29078028,CC BY,"BACKGROUND: The respiratory syncytial virus (RSV) is recognized as an important cause of respiratory tract infections. Immunocompromised patients, healthcare workers (HCWs) and children contacts are at increased risk of acquiring the infection. However, the impact of asymptomatic infection in transmission has not been well studied. Objectives: this study evaluated the frequency and viral load (VL) of RSV in nasal swab samples of individuals with different risk factors for acquiring infection in a university hospital in Sao Paulo, Brazil. METHODS: We included 196 symptomatic children and their 192 asymptomatic caregivers, 70 symptomatic and 95 asymptomatic HCWs, 43 samples from symptomatic HIV‐positive outpatients, and 100 samples of asymptomatic HIV patients in the period of 2009‐2013. RESULTS: RSV infection was detected in 10.1% (70/696) of samples, 4.4% (17/387) of asymptomatic patients, and 17.1% (53/309) from symptomatic patients. (P < .0001). The VL of symptomatic patients (4.7 log copies/mL) was significantly higher compared to asymptomatic patients (2.3 log copies/mL). RSV detection among asymptomatic caregivers (6.8%; 13/192) was significantly higher compared to other asymptomatic adults, HIV and HCWs (2.0%; 4/195; P = .0252). A close contact with an infected child at home was an important risk to RSV acquisition [OR 22.6 (95% CI 4.8‐106.7)]. Children who possibly transmitted the virus to their asymptomatic contacts had significantly higher viral load than children who probably did not transmit (P < .0001). CONCLUSIONS: According to our results, it is important to know if people circulating inside the hospital have close contact with acute respiratory infected children.",2018 May 4,"['Moreira, Luciana Peniche', 'Watanabe, Aripuana Sakurada Aranha', 'Camargo, Clarice Neves', 'Melchior, Thais Boim', 'Granato, Celso', 'Bellei, Nancy']",Influenza Other Respir Viruses,,,True
7918e26f09ad06f1336fd3f15c8c5f875ecfcabd,PMC,"Comparison of outpatient medically attended and community‐level influenza‐like illness—New York City, 2013‐2015",http://dx.doi.org/10.1111/irv.12540,PMC5907822,29350791,CC BY,"BACKGROUND: Surveillance of influenza‐like illness (ILI) in the United States is primarily conducted through medical settings despite a significant burden of non‐medically attended ILI. OBJECTIVES: To assess consistency between surveillance for respiratory viruses in outpatient and community settings using ILI surveillance from the Centers for Disease Control and Prevention Influenza Incidence Surveillance Project (IISP) and the Mobile Surveillance for Acute Respiratory Infections (ARI) and Influenza‐Like Illness in the Community (MoSAIC) Study. METHODS: The Influenza Incidence Surveillance Project conducts ILI surveillance in 3 primary care clinics in New York City, and MoSAIC conducts community‐based ILI/ARI surveillance through text messaging among a cohort of New York City residents. Both systems obtain respiratory specimens from participants with ILI/ARI and test for multiple pathogens. We conducted a retrospective review of ILI cases in IISP and MoSAIC from January 2013 to May 2015 with descriptive analyses of clinical and laboratory data. RESULTS: Five‐hundred twelve MoSAIC and 669 IISP participants met an ILI criteria (fever with cough or sore throat) and were included. Forty percent of MoSAIC participants sought care; the majority primary care. Pathogens were detected in 63% of MoSAIC and 70% of IISP cases. The relative distribution of influenza and other respiratory viruses detected was similar; however, there were statistically significant differences in the frequency that were not explained by care seeking. CONCLUSIONS: Outpatient and community‐based surveillance in the one found similar timing and relative distribution of respiratory viruses, but community surveillance in a single neighborhood may not fully capture the variations in ILI etiology that occur more broadly.",2018 May 14,"['Russell, Kate E.', 'Fowlkes, Ashley', 'Stockwell, Melissa S.', 'Vargas, Celibell Y.', 'Saiman, Lisa', 'Larson, Elaine L.', 'LaRussa, Philip', 'Di Lonardo, Steve', 'Popowich, Michael', 'St. George, Kirsten', 'Steffens, Andrea', 'Reed, Carrie']",Influenza Other Respir Viruses,,,True
ef821e34873d4752ecae41cd9dfc08a5e6db45e2,PMC,Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal,http://dx.doi.org/10.1093/jpids/piw079,PMC5907881,28073985,CC BY,"BACKGROUND: Pertussis is estimated to cause 2 percent of childhood deaths globally and is a growing public health problem in developed countries despite high vaccination coverage. Infants are at greatest risk of morbidity and mortality. Maternal vaccination during pregnancy may be effective to prevent pertussis in young infants, but population-based estimates of disease burden in infants are lacking, particularly in low-income countries. The objective of this study was to estimate the incidence of pertussis in infants less than 6 months of age in Sarlahi District, Nepal. METHODS: Nested within a population-based randomized controlled trial of influenza vaccination during pregnancy, infants were visited weekly from birth through 6 months to assess respiratory illness in the prior week. If any respiratory symptoms had occurred, a nasal swab was collected and tested with a multitarget pertussis polymerase chain reaction (PCR) assay. The prospective cohort study includes infants observed between May 2011 and August 2014. RESULTS: The incidence of PCR-confirmed Bordetella pertussis was 13.3 cases per 1000 infant-years (95% confidence interval, 7.7–21.3) in a cohort of 3483 infants with at least 1 day of follow-up. CONCLUSIONS: In a population-based active home surveillance for respiratory illness, a low risk for pertussis was estimated among infants in rural Nepal. Nepal’s immunization program, which includes a childhood whole cell pertussis vaccine, may be effective in controlling pertussis in infants.",2017 Mar 1,"['Hughes, Michelle M', 'Englund, Janet A', 'Kuypers, Jane', 'Tielsch, James M', 'Khatry, Subarna K', 'Shrestha, Laxman', 'LeClerq, Steven C', 'Steinhoff, Mark', 'Katz, Joanne']",J Pediatric Infect Dis Soc,,,True
659877b4d9d7fa18163c092cf454ec112316f2df,PMC,Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal,http://dx.doi.org/10.1093/jpids/piw079,PMC5907881,28073985,CC BY,"BACKGROUND: Pertussis is estimated to cause 2 percent of childhood deaths globally and is a growing public health problem in developed countries despite high vaccination coverage. Infants are at greatest risk of morbidity and mortality. Maternal vaccination during pregnancy may be effective to prevent pertussis in young infants, but population-based estimates of disease burden in infants are lacking, particularly in low-income countries. The objective of this study was to estimate the incidence of pertussis in infants less than 6 months of age in Sarlahi District, Nepal. METHODS: Nested within a population-based randomized controlled trial of influenza vaccination during pregnancy, infants were visited weekly from birth through 6 months to assess respiratory illness in the prior week. If any respiratory symptoms had occurred, a nasal swab was collected and tested with a multitarget pertussis polymerase chain reaction (PCR) assay. The prospective cohort study includes infants observed between May 2011 and August 2014. RESULTS: The incidence of PCR-confirmed Bordetella pertussis was 13.3 cases per 1000 infant-years (95% confidence interval, 7.7–21.3) in a cohort of 3483 infants with at least 1 day of follow-up. CONCLUSIONS: In a population-based active home surveillance for respiratory illness, a low risk for pertussis was estimated among infants in rural Nepal. Nepal’s immunization program, which includes a childhood whole cell pertussis vaccine, may be effective in controlling pertussis in infants.",2017 Mar 1,"['Hughes, Michelle M', 'Englund, Janet A', 'Kuypers, Jane', 'Tielsch, James M', 'Khatry, Subarna K', 'Shrestha, Laxman', 'LeClerq, Steven C', 'Steinhoff, Mark', 'Katz, Joanne']",J Pediatric Infect Dis Soc,,,False
f715f94955504e6dbe3963ec0ccebb0a431e7c4e,PMC,Isolation and characterization of an astrovirus causing fatal visceral gout in domestic goslings,http://dx.doi.org/10.1038/s41426-018-0074-5,PMC5908792,29674726,CC BY,"Astroviruses are recognized as a leading cause of gastroenteritis in humans and animals. They are also associated with extra-intestinal diseases, such as hepatitis in ducklings, nephritis in chickens, and encephalitis in cattle. In February 2017, a fatal infection of goslings characterized by visceral urate deposition was reported in the Shandong province, China. Our systematic investigation led to the isolation of an astrovirus, designated AAstV/Goose/CHN/2017/SD01, and similar disease was reproduced by experimental infection of healthy goslings, fulfilling Koch’s postulates. The isolated astrovirus replicated well and resulted in 100% mortality of goose embryos. Complete genome sequence analysis revealed that the isolate was genetically distinct from known astroviruses and closely related to members of the avastrovirus genogroup II. Experimental infection showed that the isolate was highly pathogenic in goslings, causing clinical signs, growth repression and in many cases mortality. Histopathological examination indicated that lesions occurred mainly in the kidneys of infected birds. However, virus-specific genomic RNA was detected in all representative tissues, and virus shedding was detected up to 12 days after inoculation, suggesting that the isolate was able to spread systemically and replicate efficiently in vivo. Collectively, our study demonstrates, for the first time, the etiological role of a genetically distinct astrovirus in the fatal infection of goslings.",2018 Apr 19,"['Zhang, Qingshui', 'Cao, Yanxin', 'Wang, Jun', 'Fu, Guanghua', 'Sun, Mengxu', 'Zhang, Lijiao', 'Meng, Li', 'Cui, Guolin', 'Huang, Yu', 'Hu, Xueying', 'Su, Jingliang']",Emerg Microbes Infect,,,True
81b992164d368b01c45fa3cc4ffd54d525e1d4b2,PMC,G-quadruplexes and G-quadruplex ligands: targets and tools in antiviral therapy,http://dx.doi.org/10.1093/nar/gky187,PMC5909458,29554280,CC BY,"G-quadruplexes (G4s) are non-canonical nucleic acids secondary structures that form within guanine-rich strands of regulatory genomic regions. G4s have been extensively described in the human genome, especially in telomeres and oncogene promoters; in recent years the presence of G4s in viruses has attracted increasing interest. Indeed, G4s have been reported in several viruses, including those involved in recent epidemics, such as the Zika and Ebola viruses. Viral G4s are usually located in regulatory regions of the genome and implicated in the control of key viral processes; in some cases, they have been involved also in viral latency. In this context, G4 ligands have been developed and tested both as tools to study the complexity of G4-mediated mechanisms in the viral life cycle, and as therapeutic agents. In general, G4 ligands showed promising antiviral activity, with G4-mediated mechanisms of action both at the genome and transcript level. This review aims to provide an updated close-up of the literature on G4s in viruses. The current state of the art of G4 ligands in antiviral research is also reported, with particular focus on the structural and physicochemical requirements for optimal biological activity. The achievements and the to-dos in the field are discussed.",2018 Apr 20,"['Ruggiero, Emanuela', 'Richter, Sara N']",Nucleic Acids Res,,,True
310f2c636d121f3a0e48ccaf6b97e4c3c8ce5abe,PMC,"Protection afforded by respirators when performing endotracheal intubation using a direct laryngoscope, GlideScope®, and i-gel® device: A randomized trial",http://dx.doi.org/10.1371/journal.pone.0195745,PMC5909605,29672533,CC BY,"Emergency physicians are at risk of infection during invasive procedures, and wearing a respirator can reduce this risk. The aim of this study was to determine whether the protection afforded by a respirator during intubation is affected by the type of airway device used. In this randomized crossover study, 26 emergency physicians underwent quantitative fit tests for a N95 respirator (cup-type or fold-type) before and during intubation with a direct laryngoscope, GlideScope®, or i-gel® airway device. The primary outcome was the fit factor value of the respirator and the secondary outcome was the level of acceptable protection provided (percentage of fit factor scores above 100). Compared with the GlideScope and i-gel device, the fit factor values and level of acceptable protection provided were lower when physicians wore the cup-type respirator while intubating using the direct laryngoscope (200 fit factor [152–200] and 200 fit factor [121.25–200] versus 166 fit factor [70–200], 100% and 100% versus 75%, respectively; all P < 0.001). There were no significant differences in the fit factor value or level of acceptable protection provided when the physicians wore the fold-type respirator while intubating using any of the three airway devices (all P > 0.05). The type of airway device used for endotracheal intubation may influence the protective performance of some types of respirators. Emergency physicians should consider the effects of airway device types on fit factor of N95 respirators, when they perform intubation at risk of infection.",2018 Apr 19,"['Kang, Hyunggoo', 'Lee, Yoonje', 'Lee, Sanghyun', 'Song, Yeongtak', 'Lim, Tae Ho', 'Oh, Jaehoon', 'Lee, Juncheol', 'Shin, Hyungoo']",PLoS One,,,True
9e768d2b61d719638c1d7ffc0da1f78927f89ee2,PMC,"Protection afforded by respirators when performing endotracheal intubation using a direct laryngoscope, GlideScope®, and i-gel® device: A randomized trial",http://dx.doi.org/10.1371/journal.pone.0195745,PMC5909605,29672533,CC BY,"Emergency physicians are at risk of infection during invasive procedures, and wearing a respirator can reduce this risk. The aim of this study was to determine whether the protection afforded by a respirator during intubation is affected by the type of airway device used. In this randomized crossover study, 26 emergency physicians underwent quantitative fit tests for a N95 respirator (cup-type or fold-type) before and during intubation with a direct laryngoscope, GlideScope®, or i-gel® airway device. The primary outcome was the fit factor value of the respirator and the secondary outcome was the level of acceptable protection provided (percentage of fit factor scores above 100). Compared with the GlideScope and i-gel device, the fit factor values and level of acceptable protection provided were lower when physicians wore the cup-type respirator while intubating using the direct laryngoscope (200 fit factor [152–200] and 200 fit factor [121.25–200] versus 166 fit factor [70–200], 100% and 100% versus 75%, respectively; all P < 0.001). There were no significant differences in the fit factor value or level of acceptable protection provided when the physicians wore the fold-type respirator while intubating using any of the three airway devices (all P > 0.05). The type of airway device used for endotracheal intubation may influence the protective performance of some types of respirators. Emergency physicians should consider the effects of airway device types on fit factor of N95 respirators, when they perform intubation at risk of infection.",2018 Apr 19,"['Kang, Hyunggoo', 'Lee, Yoonje', 'Lee, Sanghyun', 'Song, Yeongtak', 'Lim, Tae Ho', 'Oh, Jaehoon', 'Lee, Juncheol', 'Shin, Hyungoo']",PLoS One,,,False
fd1e95e046ac945ddbd0a1a515dcabf031f31244,PMC,Biliverdin reductase-A attenuated GMH-induced inflammatory response in the spleen by inhibiting toll-like receptor-4 through eNOS/NO pathway,http://dx.doi.org/10.1186/s12974-018-1155-z,PMC5910618,29678206,CC BY,"BACKGROUND: Germinal matrix hemorrhage (GMH) is a common neurologic event with high morbidity and mortality in preterm infants. Spleen has been reported to play a critical role in inflammatory responses by regulating peripheral immune cells which contributes to secondary brain injury. METHODS: The current study investigated the mechanistic role of biliverdin reductase-A (BLVRA) in the splenic response and brain damage in neonates following a collagenase GMH model. Neurological outcomes and splenic weights were assessed. Neutrophil production and infiltration were quantitated in the spleen and brain, respectively. Western blot was performed in both splenic and brain tissues to measure protein levels of toll-like receptor 4 and proinflammatory cytokines. RESULTS: BLVRA treatment alleviated GMH-induced developmental delay and attenuated splenic atrophy at 1 and 3 days after GMH. Quantification analysis showed that spleen-stored peripheral immune cells mobilized into circulation and infiltrated in the brain following GMH, which was abrogated by BLVRA administration, resulting in reduced splenic inflammatory response. Furthermore, we showed that regulation of eNOS/NO signaling by BLVRA stimulation blunted toll-like receptor-4 (TLR4) signal. The eNOS-generated NO, in part, translocated BLVRA into the nucleus, where BLVRA inhibited TLR4 expression. CONCLUSION: We revealed a BLVRA-dependent signaling pathway in modulating the splenic inflammation in response to GMH via the eNOS/NO/TLR4 pathway.",2018 Apr 20,"['Zhang, Yiting', 'Ding, Yan', 'Lu, Tai', 'Zhang, Yixin', 'Xu, Ningbo', 'McBride, Devin W.', 'Tang, Jiping', 'Zhang, John H.']",J Neuroinflammation,,,True
ac99323189694e10b699a6c845bd15b86cc06d82,PMC,Development of a quantitative loop-mediated isothermal amplification assay for the field detection of Erysiphe necator,http://dx.doi.org/10.7717/peerj.4639,PMC5912203,29692952,CC0,"Plant pathogen detection systems have been useful tools to monitor inoculum presence and initiate management schedules. More recently, a loop-mediated isothermal amplification (LAMP) assay was successfully designed for field use in the grape powdery mildew pathosystem; however, false negatives or false positives were prevalent in grower-conducted assays due to the difficulty in perceiving the magnesium pyrophosphate precipitate at low DNA concentrations. A quantitative LAMP (qLAMP) assay using a fluorescence resonance energy transfer-based probe was assessed by grape growers in the Willamette Valley of Oregon. Custom impaction spore samplers were placed at a research vineyard and six commercial vineyard locations, and were tested bi-weekly by the lab and by growers. Grower-conducted qLAMP assays used a beta-version of the Smart-DART handheld LAMP reaction devices (Diagenetix, Inc., Honolulu, HI, USA), connected to Android 4.4 enabled, Bluetooth-capable Nexus 7 tablets for output. Quantification by a quantitative PCR assay was assumed correct to compare the lab and grower qLAMP assay quantification. Growers were able to conduct and interpret qLAMP results; however, the Erysiphe necator inoculum quantification was unreliable using the beta-Smart-DART devices. The qLAMP assay developed was sensitive to one spore in early testing of the assay, but decreased to >20 spores by the end of the trial. The qLAMP assay is not likely a suitable management tool for grape powdery mildew due to losses in sensitivity and decreasing costs and portability for other, more reliable molecular tools.",2018 Apr 20,"['Thiessen, Lindsey D.', 'Neill, Tara M.', 'Mahaffee, Walter F.']",PeerJ,,,True
53ac5d89055610d2b199e67d8438eba84dbfcf84,PMC,Dynamics of the seasonal airborne propagation of Staphylococcus aureus in academic dental clinics,http://dx.doi.org/10.1590/1678-7757-2017-0141,PMC5912401,29641749,CC BY,"OBJECTIVE: Staphylococcus aureus strains can be disseminated during dental treatments and occasionally lead to the contamination and infection of patients and dentists, which is an important public health problem. The dynamics of the airborne propagation and the genetic diversity of S. aureus isolated in an academic dental clinic environment were investigated using isoenzyme typing. MATERIAL AND METHODS: The isoenzymes of 44 previously reported isolates were obtained from fresh cultures and extracted using glass beads. Nine isoenzymes were investigated using multilocus enzyme electrophoresis (MLEE). The genetic diversity and relationship among the strains (electrophoretic type – ET) were determined using statistics previously described by Nei (25) (1972) and the SAHN grouping method (UPGMA algorithm). RESULTS: Clonal pattern analyses indicated a high level of genetic polymorphism occurring among the 33 ETs, which were grouped into five taxa. Each taxon presented one or more clusters that were moderately related and that contained two or more identical/highly related isolates, revealing seasonal airborne propagation in these dental clinic environments. CONCLUSIONS: These data suggest the occurrence of active microevolutionary processes in S. aureus as well as the possibility of environmental propagation during a 14-month time span. Such findings are important to show that multiuser academic dental clinics can retain certain strains that are spreadable to different niches.",2018 Mar 26,"['Bernardo, Wagner Luiz de Carvalho', 'da Silva, Jeferson Júnior', 'Höfling, José Francisco', 'Rosa, Edvaldo Antônio Ribeiro', 'Boriollo, Marcelo Fabiano Gomes']",J Appl Oral Sci,,,True
d71ba68f8d3e03e0a16d0ab59675786bae69b6ab,PMC,"Ebolavirus diagnosis made simple, comparable and faster than molecular detection methods: preparing for the future",http://dx.doi.org/10.1186/s12985-018-0985-8,PMC5914028,29685158,CC BY,"BACKGROUND: The 2014/2015 Ebolavirus outbreak resulted in more than 28,000 cases and 11,323 reported deaths, as of March 2016. Domestic transmission of the Guinea strain associated with the outbreak occurred mainly in six African countries, and international transmission was reported in four countries. Outbreak management was limited by the inability to rapidly diagnose infected cases. A further fifteen countries in Africa are predicted to be at risk of Ebolavirus outbreaks in the future as a consequence of climate change and urbanization. Early detection of cases and reduction of transmission rates is critical to prevent and manage future severe outbreaks. We designed a rapid assay for detection of Ebolavirus using recombinase polymerase amplification, a rapid isothermal amplification technology that can be combined with portable lateral flow detection technology. The developed rapid assay operates in 30 min and was comparable with real-time TaqMan™ PCR. METHODS: Designed, screened, selected and optimized oligonucleotides using the NP coding region from Ebola Zaire virus (Guinea strain). We determined the analytical sensitivity of our Ebola rapid molecular test by testing selected primers and probe with tenfold serial dilutions (1.34 × 10(10−) 1.34 × 10(1) copies/μL) of cloned NP gene from Mayinga strain of Zaire ebolavirus in pCAGGS vector, and serially diluted cultured Ebolavirus as established by real-time TaqMan™ PCR that was performed using ABI7500 in Fast Mode. We tested extracted and reverse transcribed RNA from cultured Zaire ebolavirus strains – Mayinga, Gueckedou C05, Gueckedou C07, Makona, Kissidougou and Kiwit. We determined the analytical specificity of our assay with related viruses: Marburg, Ebola Reston and Ebola Sudan. We further tested for Dengue virus 1–4, Plasmodium falciparum and West Nile Virus (Kunjin strain). RESULTS: The assay had a detection limit of 134 copies per μL of plasmid containing the NP gene of Ebolavirus Mayinga, and cultured Ebolavirus and was highly specific for the Zaire ebolavirus species, including the Guinea strain responsible for the 2014/2015 outbreak. The assay did not detect related viruses like Marburg, Reston, or Sudan viruses, and other pathogens likely to be isolated from clinical samples. CONCLUSIONS: Our assay could be suitable for implementation in district and primary health laboratories, as only a heating block and centrifuge is required for operation. The technique could provide a pathway for rapid screening of patients and animals for improved management of outbreaks.",2018 Apr 23,"['James, Ameh S.', 'Todd, Shawn', 'Pollak, Nina M.', 'Marsh, Glenn A.', 'Macdonald, Joanne']",Virol J,,,True
6b0f17a81d8f9849d4937aafbdbf74ec71820811,PMC,Blockade of the C5a–C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV,http://dx.doi.org/10.1038/s41426-018-0063-8,PMC5915580,29691378,CC BY,"The pathogenesis of highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) remains poorly understood. In a previous study, we established an hDPP4-transgenic (hDPP4-Tg) mouse model in which MERS-CoV infection causes severe acute respiratory failure and high mortality accompanied by an elevated secretion of cytokines and chemokines. Since excessive complement activation is an important factor that contributes to acute lung injury after viral infection, in this study, we investigated the role of complement in MERS-CoV-induced lung damage. Our study showed that complement was excessively activated in MERS-CoV-infected hDPP4-Tg mice through observations of increased concentrations of the C5a and C5b-9 complement activation products in sera and lung tissues, respectively. Interestingly, blocking C5a production by targeting its receptor, C5aR, alleviated lung and spleen tissue damage and reduced inflammatory responses. More importantly, anti-C5aR antibody treatment led to decreased viral replication in lung tissues. Furthermore, compared with the sham treatment control, apoptosis of splenic cells was less pronounced in the splenic white pulp of treated mice, and greater number of proliferating splenic cells, particularly in the red pulp, was observed. These data indicate that (1) dysregulated host immune responses contribute to the severe outcome of MERS; (2) excessive complement activation, triggered by MERS-CoV infection, promote such dysregulation; and (3) blockade of the C5a–C5aR axis lead to the decreased tissue damage induced by MERS-CoV infection, as manifested by reduced apoptosis and T cell regeneration in the spleen. Therefore, the results of this study suggest a new strategy for clinical intervention and adjunctive treatment in MERS-CoV cases.",2018 Apr 24,"['Jiang, Yuting', 'Zhao, Guangyu', 'Song, Nianping', 'Li, Pei', 'Chen, Yuehong', 'Guo, Yan', 'Li, Junfeng', 'Du, Lanying', 'Jiang, Shibo', 'Guo, Renfeng', 'Sun, Shihui', 'Zhou, Yusen']",Emerg Microbes Infect,,,True
bd96aabb0e4aa01c5310bf23827eb32168779a7c,PMC,The Efficacy of the Interferon Alpha/Beta Response versus Arboviruses Is Temperature Dependent,http://dx.doi.org/10.1128/mBio.00535-18,PMC5915735,29691338,CC BY,"Interferon alpha/beta (IFN-α/β) is a critical mediator of protection against most viruses, with host survival frequently impossible in its absence. Many studies have investigated the pathways involved in the induction of IFN-α/β after virus infection and the resultant upregulation of antiviral IFN-stimulated genes (ISGs) through IFN-α/β receptor complex signaling. However, other than examining the effects of genetic deletion of induction or effector pathway components, little is known regarding the functionality of these responses in intact hosts and whether host genetic or environmental factors might influence their potency. Here, we demonstrate that the IFN-α/β response against multiple arthropod-vectored viruses, which replicate over a wide temperature range, is extremely sensitive to fluctuations in temperature, exhibiting reduced antiviral efficacy at subnormal cellular temperatures and increased efficacy at supranormal temperatures. The effect involves both IFN-α/β and ISG upregulation pathways with a major aspect of altered potency reflecting highly temperature-dependent transcription of IFN response genes that leads to altered IFN-α/β and ISG protein levels. Discordantly, signaling steps prior to transcription that were examined showed the opposite effect from gene transcription, with potentiation at low temperature and inhibition at high temperature. Finally, we demonstrate that by lowering the temperature of mice, chikungunya arbovirus replication and disease are exacerbated in an IFN-α/β-dependent manner. This finding raises the potential for use of hyperthermia as a therapeutic modality for viral infections and in other contexts such as antitumor therapy. The increased IFN-α/β efficacy at high temperatures may also reflect an innate immune-relevant aspect of the febrile response.",2018 Apr 24,"['Lane, Whitney C.', 'Dunn, Matthew D.', 'Gardner, Christina L.', 'Lam, L. K. Metthew', 'Watson, Alan M.', 'Hartman, Amy L.', 'Ryman, Kate D.', 'Klimstra, William B.']",mBio,,,True
4219285f04df38ffeb2ca1aa43453ffa8da44777,PMC,The Efficacy of the Interferon Alpha/Beta Response versus Arboviruses Is Temperature Dependent,http://dx.doi.org/10.1128/mBio.00535-18,PMC5915735,29691338,CC BY,"Interferon alpha/beta (IFN-α/β) is a critical mediator of protection against most viruses, with host survival frequently impossible in its absence. Many studies have investigated the pathways involved in the induction of IFN-α/β after virus infection and the resultant upregulation of antiviral IFN-stimulated genes (ISGs) through IFN-α/β receptor complex signaling. However, other than examining the effects of genetic deletion of induction or effector pathway components, little is known regarding the functionality of these responses in intact hosts and whether host genetic or environmental factors might influence their potency. Here, we demonstrate that the IFN-α/β response against multiple arthropod-vectored viruses, which replicate over a wide temperature range, is extremely sensitive to fluctuations in temperature, exhibiting reduced antiviral efficacy at subnormal cellular temperatures and increased efficacy at supranormal temperatures. The effect involves both IFN-α/β and ISG upregulation pathways with a major aspect of altered potency reflecting highly temperature-dependent transcription of IFN response genes that leads to altered IFN-α/β and ISG protein levels. Discordantly, signaling steps prior to transcription that were examined showed the opposite effect from gene transcription, with potentiation at low temperature and inhibition at high temperature. Finally, we demonstrate that by lowering the temperature of mice, chikungunya arbovirus replication and disease are exacerbated in an IFN-α/β-dependent manner. This finding raises the potential for use of hyperthermia as a therapeutic modality for viral infections and in other contexts such as antitumor therapy. The increased IFN-α/β efficacy at high temperatures may also reflect an innate immune-relevant aspect of the febrile response.",2018 Apr 24,"['Lane, Whitney C.', 'Dunn, Matthew D.', 'Gardner, Christina L.', 'Lam, L. K. Metthew', 'Watson, Alan M.', 'Hartman, Amy L.', 'Ryman, Kate D.', 'Klimstra, William B.']",mBio,,,False
a482276226b60bab80fce993caaf4ef9a764afa4,PMC,The Efficacy of the Interferon Alpha/Beta Response versus Arboviruses Is Temperature Dependent,http://dx.doi.org/10.1128/mBio.00535-18,PMC5915735,29691338,CC BY,"Interferon alpha/beta (IFN-α/β) is a critical mediator of protection against most viruses, with host survival frequently impossible in its absence. Many studies have investigated the pathways involved in the induction of IFN-α/β after virus infection and the resultant upregulation of antiviral IFN-stimulated genes (ISGs) through IFN-α/β receptor complex signaling. However, other than examining the effects of genetic deletion of induction or effector pathway components, little is known regarding the functionality of these responses in intact hosts and whether host genetic or environmental factors might influence their potency. Here, we demonstrate that the IFN-α/β response against multiple arthropod-vectored viruses, which replicate over a wide temperature range, is extremely sensitive to fluctuations in temperature, exhibiting reduced antiviral efficacy at subnormal cellular temperatures and increased efficacy at supranormal temperatures. The effect involves both IFN-α/β and ISG upregulation pathways with a major aspect of altered potency reflecting highly temperature-dependent transcription of IFN response genes that leads to altered IFN-α/β and ISG protein levels. Discordantly, signaling steps prior to transcription that were examined showed the opposite effect from gene transcription, with potentiation at low temperature and inhibition at high temperature. Finally, we demonstrate that by lowering the temperature of mice, chikungunya arbovirus replication and disease are exacerbated in an IFN-α/β-dependent manner. This finding raises the potential for use of hyperthermia as a therapeutic modality for viral infections and in other contexts such as antitumor therapy. The increased IFN-α/β efficacy at high temperatures may also reflect an innate immune-relevant aspect of the febrile response.",2018 Apr 24,"['Lane, Whitney C.', 'Dunn, Matthew D.', 'Gardner, Christina L.', 'Lam, L. K. Metthew', 'Watson, Alan M.', 'Hartman, Amy L.', 'Ryman, Kate D.', 'Klimstra, William B.']",mBio,,,False
bac1303e901e09cd40af291b231fe321bc83fcc6,PMC,The Efficacy of the Interferon Alpha/Beta Response versus Arboviruses Is Temperature Dependent,http://dx.doi.org/10.1128/mBio.00535-18,PMC5915735,29691338,CC BY,"Interferon alpha/beta (IFN-α/β) is a critical mediator of protection against most viruses, with host survival frequently impossible in its absence. Many studies have investigated the pathways involved in the induction of IFN-α/β after virus infection and the resultant upregulation of antiviral IFN-stimulated genes (ISGs) through IFN-α/β receptor complex signaling. However, other than examining the effects of genetic deletion of induction or effector pathway components, little is known regarding the functionality of these responses in intact hosts and whether host genetic or environmental factors might influence their potency. Here, we demonstrate that the IFN-α/β response against multiple arthropod-vectored viruses, which replicate over a wide temperature range, is extremely sensitive to fluctuations in temperature, exhibiting reduced antiviral efficacy at subnormal cellular temperatures and increased efficacy at supranormal temperatures. The effect involves both IFN-α/β and ISG upregulation pathways with a major aspect of altered potency reflecting highly temperature-dependent transcription of IFN response genes that leads to altered IFN-α/β and ISG protein levels. Discordantly, signaling steps prior to transcription that were examined showed the opposite effect from gene transcription, with potentiation at low temperature and inhibition at high temperature. Finally, we demonstrate that by lowering the temperature of mice, chikungunya arbovirus replication and disease are exacerbated in an IFN-α/β-dependent manner. This finding raises the potential for use of hyperthermia as a therapeutic modality for viral infections and in other contexts such as antitumor therapy. The increased IFN-α/β efficacy at high temperatures may also reflect an innate immune-relevant aspect of the febrile response.",2018 Apr 24,"['Lane, Whitney C.', 'Dunn, Matthew D.', 'Gardner, Christina L.', 'Lam, L. K. Metthew', 'Watson, Alan M.', 'Hartman, Amy L.', 'Ryman, Kate D.', 'Klimstra, William B.']",mBio,,,False
fceacfc522a5a119a74b1d0ffeed72b1a2847c91,PMC,The Efficacy of the Interferon Alpha/Beta Response versus Arboviruses Is Temperature Dependent,http://dx.doi.org/10.1128/mBio.00535-18,PMC5915735,29691338,CC BY,"Interferon alpha/beta (IFN-α/β) is a critical mediator of protection against most viruses, with host survival frequently impossible in its absence. Many studies have investigated the pathways involved in the induction of IFN-α/β after virus infection and the resultant upregulation of antiviral IFN-stimulated genes (ISGs) through IFN-α/β receptor complex signaling. However, other than examining the effects of genetic deletion of induction or effector pathway components, little is known regarding the functionality of these responses in intact hosts and whether host genetic or environmental factors might influence their potency. Here, we demonstrate that the IFN-α/β response against multiple arthropod-vectored viruses, which replicate over a wide temperature range, is extremely sensitive to fluctuations in temperature, exhibiting reduced antiviral efficacy at subnormal cellular temperatures and increased efficacy at supranormal temperatures. The effect involves both IFN-α/β and ISG upregulation pathways with a major aspect of altered potency reflecting highly temperature-dependent transcription of IFN response genes that leads to altered IFN-α/β and ISG protein levels. Discordantly, signaling steps prior to transcription that were examined showed the opposite effect from gene transcription, with potentiation at low temperature and inhibition at high temperature. Finally, we demonstrate that by lowering the temperature of mice, chikungunya arbovirus replication and disease are exacerbated in an IFN-α/β-dependent manner. This finding raises the potential for use of hyperthermia as a therapeutic modality for viral infections and in other contexts such as antitumor therapy. The increased IFN-α/β efficacy at high temperatures may also reflect an innate immune-relevant aspect of the febrile response.",2018 Apr 24,"['Lane, Whitney C.', 'Dunn, Matthew D.', 'Gardner, Christina L.', 'Lam, L. K. Metthew', 'Watson, Alan M.', 'Hartman, Amy L.', 'Ryman, Kate D.', 'Klimstra, William B.']",mBio,,,False
9c88d74af46e4bd919cdd65a2c7977824e796811,PMC,The Efficacy of the Interferon Alpha/Beta Response versus Arboviruses Is Temperature Dependent,http://dx.doi.org/10.1128/mBio.00535-18,PMC5915735,29691338,CC BY,"Interferon alpha/beta (IFN-α/β) is a critical mediator of protection against most viruses, with host survival frequently impossible in its absence. Many studies have investigated the pathways involved in the induction of IFN-α/β after virus infection and the resultant upregulation of antiviral IFN-stimulated genes (ISGs) through IFN-α/β receptor complex signaling. However, other than examining the effects of genetic deletion of induction or effector pathway components, little is known regarding the functionality of these responses in intact hosts and whether host genetic or environmental factors might influence their potency. Here, we demonstrate that the IFN-α/β response against multiple arthropod-vectored viruses, which replicate over a wide temperature range, is extremely sensitive to fluctuations in temperature, exhibiting reduced antiviral efficacy at subnormal cellular temperatures and increased efficacy at supranormal temperatures. The effect involves both IFN-α/β and ISG upregulation pathways with a major aspect of altered potency reflecting highly temperature-dependent transcription of IFN response genes that leads to altered IFN-α/β and ISG protein levels. Discordantly, signaling steps prior to transcription that were examined showed the opposite effect from gene transcription, with potentiation at low temperature and inhibition at high temperature. Finally, we demonstrate that by lowering the temperature of mice, chikungunya arbovirus replication and disease are exacerbated in an IFN-α/β-dependent manner. This finding raises the potential for use of hyperthermia as a therapeutic modality for viral infections and in other contexts such as antitumor therapy. The increased IFN-α/β efficacy at high temperatures may also reflect an innate immune-relevant aspect of the febrile response.",2018 Apr 24,"['Lane, Whitney C.', 'Dunn, Matthew D.', 'Gardner, Christina L.', 'Lam, L. K. Metthew', 'Watson, Alan M.', 'Hartman, Amy L.', 'Ryman, Kate D.', 'Klimstra, William B.']",mBio,,,False
6e6ccb3584bdbdd4c98706850a6a4c94a3ff9c0c,PMC,The Efficacy of the Interferon Alpha/Beta Response versus Arboviruses Is Temperature Dependent,http://dx.doi.org/10.1128/mBio.00535-18,PMC5915735,29691338,CC BY,"Interferon alpha/beta (IFN-α/β) is a critical mediator of protection against most viruses, with host survival frequently impossible in its absence. Many studies have investigated the pathways involved in the induction of IFN-α/β after virus infection and the resultant upregulation of antiviral IFN-stimulated genes (ISGs) through IFN-α/β receptor complex signaling. However, other than examining the effects of genetic deletion of induction or effector pathway components, little is known regarding the functionality of these responses in intact hosts and whether host genetic or environmental factors might influence their potency. Here, we demonstrate that the IFN-α/β response against multiple arthropod-vectored viruses, which replicate over a wide temperature range, is extremely sensitive to fluctuations in temperature, exhibiting reduced antiviral efficacy at subnormal cellular temperatures and increased efficacy at supranormal temperatures. The effect involves both IFN-α/β and ISG upregulation pathways with a major aspect of altered potency reflecting highly temperature-dependent transcription of IFN response genes that leads to altered IFN-α/β and ISG protein levels. Discordantly, signaling steps prior to transcription that were examined showed the opposite effect from gene transcription, with potentiation at low temperature and inhibition at high temperature. Finally, we demonstrate that by lowering the temperature of mice, chikungunya arbovirus replication and disease are exacerbated in an IFN-α/β-dependent manner. This finding raises the potential for use of hyperthermia as a therapeutic modality for viral infections and in other contexts such as antitumor therapy. The increased IFN-α/β efficacy at high temperatures may also reflect an innate immune-relevant aspect of the febrile response.",2018 Apr 24,"['Lane, Whitney C.', 'Dunn, Matthew D.', 'Gardner, Christina L.', 'Lam, L. K. Metthew', 'Watson, Alan M.', 'Hartman, Amy L.', 'Ryman, Kate D.', 'Klimstra, William B.']",mBio,,,False
37c33b4e94acac48c5826db43d99964d3ad2ba03,PMC,The Efficacy of the Interferon Alpha/Beta Response versus Arboviruses Is Temperature Dependent,http://dx.doi.org/10.1128/mBio.00535-18,PMC5915735,29691338,CC BY,"Interferon alpha/beta (IFN-α/β) is a critical mediator of protection against most viruses, with host survival frequently impossible in its absence. Many studies have investigated the pathways involved in the induction of IFN-α/β after virus infection and the resultant upregulation of antiviral IFN-stimulated genes (ISGs) through IFN-α/β receptor complex signaling. However, other than examining the effects of genetic deletion of induction or effector pathway components, little is known regarding the functionality of these responses in intact hosts and whether host genetic or environmental factors might influence their potency. Here, we demonstrate that the IFN-α/β response against multiple arthropod-vectored viruses, which replicate over a wide temperature range, is extremely sensitive to fluctuations in temperature, exhibiting reduced antiviral efficacy at subnormal cellular temperatures and increased efficacy at supranormal temperatures. The effect involves both IFN-α/β and ISG upregulation pathways with a major aspect of altered potency reflecting highly temperature-dependent transcription of IFN response genes that leads to altered IFN-α/β and ISG protein levels. Discordantly, signaling steps prior to transcription that were examined showed the opposite effect from gene transcription, with potentiation at low temperature and inhibition at high temperature. Finally, we demonstrate that by lowering the temperature of mice, chikungunya arbovirus replication and disease are exacerbated in an IFN-α/β-dependent manner. This finding raises the potential for use of hyperthermia as a therapeutic modality for viral infections and in other contexts such as antitumor therapy. The increased IFN-α/β efficacy at high temperatures may also reflect an innate immune-relevant aspect of the febrile response.",2018 Apr 24,"['Lane, Whitney C.', 'Dunn, Matthew D.', 'Gardner, Christina L.', 'Lam, L. K. Metthew', 'Watson, Alan M.', 'Hartman, Amy L.', 'Ryman, Kate D.', 'Klimstra, William B.']",mBio,,,False
c2fb69c45cf188766e55206f052919e26e236abc,PMC,The Efficacy of the Interferon Alpha/Beta Response versus Arboviruses Is Temperature Dependent,http://dx.doi.org/10.1128/mBio.00535-18,PMC5915735,29691338,CC BY,"Interferon alpha/beta (IFN-α/β) is a critical mediator of protection against most viruses, with host survival frequently impossible in its absence. Many studies have investigated the pathways involved in the induction of IFN-α/β after virus infection and the resultant upregulation of antiviral IFN-stimulated genes (ISGs) through IFN-α/β receptor complex signaling. However, other than examining the effects of genetic deletion of induction or effector pathway components, little is known regarding the functionality of these responses in intact hosts and whether host genetic or environmental factors might influence their potency. Here, we demonstrate that the IFN-α/β response against multiple arthropod-vectored viruses, which replicate over a wide temperature range, is extremely sensitive to fluctuations in temperature, exhibiting reduced antiviral efficacy at subnormal cellular temperatures and increased efficacy at supranormal temperatures. The effect involves both IFN-α/β and ISG upregulation pathways with a major aspect of altered potency reflecting highly temperature-dependent transcription of IFN response genes that leads to altered IFN-α/β and ISG protein levels. Discordantly, signaling steps prior to transcription that were examined showed the opposite effect from gene transcription, with potentiation at low temperature and inhibition at high temperature. Finally, we demonstrate that by lowering the temperature of mice, chikungunya arbovirus replication and disease are exacerbated in an IFN-α/β-dependent manner. This finding raises the potential for use of hyperthermia as a therapeutic modality for viral infections and in other contexts such as antitumor therapy. The increased IFN-α/β efficacy at high temperatures may also reflect an innate immune-relevant aspect of the febrile response.",2018 Apr 24,"['Lane, Whitney C.', 'Dunn, Matthew D.', 'Gardner, Christina L.', 'Lam, L. K. Metthew', 'Watson, Alan M.', 'Hartman, Amy L.', 'Ryman, Kate D.', 'Klimstra, William B.']",mBio,,,False
454c099b504f30d078e4fff12a3212dcc5567e97,PMC,"Impact of infectious diseases on population health using incidence-based disability-adjusted life years (DALYs): results from the Burden of Communicable Diseases in Europe study, European Union and European Economic Area countries, 2009 to 2013",http://dx.doi.org/10.2807/1560-7917.ES.2018.23.16.17-00454,PMC5915974,29692315,CC BY,"The Burden of Communicable Diseases in Europe (BCoDE) study aimed to calculate disability-adjusted life years (DALYs) for 31 selected diseases in the European Union (EU) and European Economic Area (EEA). Methods: DALYs were estimated using an incidence-based and pathogen-based approach. Incidence was estimated through assessment of data availability and quality, and a correction was applied for under-estimation. Calculation of DALYs was performed with the BCoDE software toolkit without applying time discounting and age-weighting. Results: We estimated that one in 14 inhabitants experienced an infectious disease episode for a total burden of 1.38 million DALYs (95% uncertainty interval (UI): 1.25–1.5) between 2009 and 2013; 76% of which was related to the acute phase of the infection and its short-term complications. Influenza had the highest burden (30% of the total burden), followed by tuberculosis, human immunodeficiency virus (HIV) infection/AIDS and invasive pneumococcal disease (IPD). Men had the highest burden measured in DALYs (60% of the total), adults 65 years of age and over had 24% and children less than 5 years of age had 11%. Age group-specific burden showed that infants (less than 1 year of age) and elderly people (80 years of age and over) experienced the highest burden. Conclusions: These results provide baseline estimates for evaluating infectious disease prevention and control strategies. The study promotes an evidence-based approach to describing population health and assessing surveillance data availability and quality, and provides information for the planning and prioritisation of limited resources in infectious disease prevention and control.",2018 Apr 19,"['Cassini, Alessandro', 'Colzani, Edoardo', 'Pini, Alessandro', 'Mangen, Marie-Josee J', 'Plass, Dietrich', 'McDonald, Scott A', 'Maringhini, Guido', 'van Lier, Alies', 'Haagsma, Juanita A', 'Havelaar, Arie H', 'Kramarz, Piotr', 'Kretzschmar, Mirjam E', None]",Euro Surveill,,,True
6ac37ecc83bd4e2f6a28476954dd962e10b1b69c,PMC,Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone,http://dx.doi.org/10.1038/s41413-018-0014-y,PMC5916877,29707402,CC BY,"Discriminating sterile inflammation from infection, especially in cases of aseptic loosening versus an actual prosthetic joint infection, is challenging and has significant treatment implications. Our goal was to evaluate a novel human monoclonal antibody (mAb) probe directed against the Gram-positive bacterial surface molecule lipoteichoic acid (LTA). Specificity and affinity were assessed in vitro. We then radiolabeled the anti-LTA mAb and evaluated its effectiveness as a diagnostic imaging tool for detecting infection via immunoPET imaging in an in vivo mouse model of prosthetic joint infection (PJI). In vitro and ex vivo binding of the anti-LTA mAb to pathogenic bacteria was measured with Octet, ELISA, and flow cytometry. The in vivo PJI mouse model was assessed using traditional imaging modalities, including positron emission tomography (PET) with [(18)F]FDG and [(18)F]NaF as well as X-ray computed tomography (CT), before being evaluated with the zirconium-89-labeled antibody specific for LTA ([(89)Zr]SAC55). The anti-LTA mAb exhibited specific binding in vitro to LTA-expressing bacteria. Results from imaging showed that our model could reliably simulate infection at the surgical site by bioluminescent imaging, conventional PET tracer imaging, and bone morphological changes by CT. One day following injection of both the radiolabeled anti-LTA and isotype control antibodies, the anti-LTA antibody demonstrated significantly greater (P < 0.05) uptake at S. aureus-infected prosthesis sites over either the same antibody at sterile prosthesis sites or of control non-specific antibody at infected prosthesis sites. Taken together, the radiolabeled anti-LTA mAb, [(89)Zr]SAC55, may serve as a valuable diagnostic molecular imaging probe to help distinguish between sterile inflammation and infection in the setting of PJI. Future studies are needed to determine whether these findings will translate to human PJI.",2018 Apr 25,"['Pickett, Julie E.', 'Thompson, John M.', 'Sadowska, Agnieszka', 'Tkaczyk, Christine', 'Sellman, Bret R.', 'Minola, Andrea', 'Corti, Davide', 'Lanzavecchia, Antonio', 'Miller, Lloyd S.', 'Thorek, Daniel LJ']",Bone Res,,,True
01cadfe2bb23b6989e57fce2ba744691557faa93,PMC,Positive experiences of volunteers working in deployable laboratories in West Africa during the Ebola outbreak,http://dx.doi.org/10.1371/journal.pone.0196320,PMC5919609,29698521,CC BY,"The largest outbreak of Ebola virus disease ever started in West Africa in December 2013; it created a pressing need to expand the workforce dealing with it. The aim of this study was to gain insight into the experiences of volunteers from the European Union who worked in deployable laboratories in West Africa during the outbreak. This study is part of the EMERGE project. We assessed the experiences of 251 volunteers with a 19-item online questionnaire. The questions asked about positive aspects of volunteering such as learning new skills, establishing a new path in life, and changing life values. Other questionnaire subjects were the compliance to follow-up measures, the extent to which volunteers felt these measures restricted their daily activities, the fear of stigmatization, and worries about becoming infected or infecting their families. The volunteers reported positive effects that reached far beyond their daily work, such as changes in life priorities and a greater appreciation of the value of their own lives. Although the volunteers did not feel that temperature monitoring restricted their daily activities, full compliance to temperature monitoring and reporting it to the authorities was low. The volunteers did not fear Ebola infection for themselves or their families and were not afraid of stigmatization. With respect to the burden on the families, 50% reported that their family members were worried that the volunteer would be infected with Ebola virus. Altogether, the positive experiences of the volunteers in this study far outweigh the negative implications and constitute an important argument for inspiring people who intend to join such missions and for motivating the hesitant ones.",2018 Apr 26,"['Belfroid, Evelien', 'Mollers, Madelief', 'Smit, Pieter W.', 'Hulscher, Marlies', 'Koopmans, Marion', 'Reusken, Chantal', 'Timen, Aura']",PLoS One,,,True
e18f75d74176ea6eff4a4e8ef6ad0a0836a92a5e,PMC,Clinical manifestations in infants and children with Mycoplasma pneumoniae infection,http://dx.doi.org/10.1371/journal.pone.0195288,PMC5919654,29698412,CC BY,"BACKGROUND: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in older children. Pulmonary and extra-pulmonary symptoms associated with M. pneumoniae infection are reported. M. pneumoniae is mainly epidemic in Denmark with the recurrence every 4-7(th) year. AIMS: Retrospectively, to describe the epidemiology and clinical features, in infants and children, during the M. pneumoniae epidemic in 2010 and 2011. METHODS: All children under the age of 16 that were tested for M. pneumoniae during the period 01.02.2010–31.01.2012 were included. Medical charts, as well as radiological findings, were reviewed for all children with M. pneumoniae. A post-hoc analysis of viral co-infections was done on part of the cohort. RESULTS: 134 of 746 children were tested positive for M. pneumoniae by PCR or serology. Positive tests were found in 65% of children seven years and older, in 30% of 2-6-year-olds and 4% of infants (less than two years of age). Viral co-infection was found in 27% of the tested samples. The clinical presentation was a cough, asthma-like symptoms and low-grade fever. Extra-pulmonary symptoms were common and presented as nausea/vomiting by 33% of the children and skin manifestations by 25%. 84% of the children had a chest x-ray taken, and there were positive radiological findings in 94% of these. CONCLUSION: M. pneumoniae also affected infants and young children and symptoms were similar to infections with respiratory viruses, but severe LRTI were also seen. During an up-coming epidemic, assessment of extra-pulmonary manifestations can be helpful when diagnosing M. pneumoniae infections.",2018 Apr 26,"['Søndergaard, Mia Johanna', 'Friis, Martin Barfred', 'Hansen, Dennis Schrøder', 'Jørgensen, Inger Merete']",PLoS One,,,True
da7fb6a91b2595d009f5e9f60a45cc0a45fceac7,PMC,Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds,http://dx.doi.org/10.3389/fmicb.2018.00750,PMC5920040,29731743,CC BY,"Phosphorodiamidate morpholino oligomers (PMO) are short single-stranded DNA analogs that are built upon a backbone of morpholine rings connected by phosphorodiamidate linkages. As uncharged nucleic acid analogs, PMO bind to complementary sequences of target mRNA by Watson–Crick base pairing to block protein translation through steric blockade. PMO interference of viral protein translation operates independently of RNase H. Meanwhile, PMO are resistant to a variety of enzymes present in biologic fluids, a characteristic that makes them highly suitable for in vivo applications. Notably, PMO-based therapy for Duchenne muscular dystrophy (DMD) has been approved by the United States Food and Drug Administration which is now a hallmark for PMO-based antisense therapy. In this review, the development history of PMO, delivery methods for improving cellular uptake of neutrally charged PMO molecules, past studies of PMO antagonism against RNA and DNA viruses, PMO target selection, and remaining questions of PMO antiviral strategies are discussed in detail and new insights are provided.",2018 Apr 20,"['Nan, Yuchen', 'Zhang, Yan-Jin']",Front Microbiol,,,True
272b73f1f4852e9c37a862eab96131a5d27e1892,PMC,Cytokine storms are primarily responsible for the rapid death of ducklings infected with duck hepatitis A virus type 1,http://dx.doi.org/10.1038/s41598-018-24729-w,PMC5920089,29700351,CC BY,"Duck hepatitis A virus type 1 (DHAV-1) is one of the most harmful pathogens in the duck industry. The infection of adult ducks with DHAV-1 was previously shown to result in transient cytokine storms in their kidneys. To understand how DHAV-1 infection impacts the host liver, we conducted animal experiments with the virulent CH DHAV-1 strain and the attenuated CH60 commercial vaccine strain. Visual observation and standard hematoxylin and eosin staining were performed to detect pathological damage in the liver, and viral copy numbers and cytokine expression in the liver were evaluated by quantitative PCR. The CH strain (10(8.4) copies/mg) had higher viral titers than the CH60 strain (10(4.9) copies/mg) in the liver and caused ecchymotic hemorrhaging on the liver surface. Additionally, livers from ducklings inoculated with the CH strain were significantly infiltrated by numerous red blood cells, accompanied by severe cytokine storms, but similar signs were not observed in the livers of ducklings inoculated with the CH60 strain. In conclusion, the severe cytokine storm caused by the CH strain apparently induces hemorrhagic lesions in the liver, which might be a key factor in the rapid death of ducklings.",2018 Apr 26,"['Xie, Jinyan', 'Wang, Mingshu', 'Cheng, Anchun', 'Zhao, Xin-Xin', 'Liu, Mafeng', 'Zhu, Dekang', 'Chen, Shun', 'Jia, Renyong', 'Yang, Qiao', 'Wu, Ying', 'Zhang, Shaqiu', 'Liu, Yunya', 'Yu, Yanling', 'Zhang, Ling', 'Sun, Kunfeng', 'Chen, Xiaoyue']",Sci Rep,,,True
b31dc72ffc01a849e4f2fce7ddd09067cfc82770,PMC,Temporal relationship between antibiotic use and respiratory virus activities in the Republic of Korea: a time-series analysis,http://dx.doi.org/10.1186/s13756-018-0347-8,PMC5922305,29736236,CC BY,"BACKGROUND: Inappropriate use of antibiotics increases resistance and reduces their effectiveness. Despite evidence-based guidelines, antibiotics are still commonly used to treat infections likely caused by respiratory viruses. In this study, we examined the temporal relationships between antibiotic usage and respiratory infections in the Republic of Korea. METHODS: The number of monthly antibiotic prescriptions and the incidence of acute respiratory tract infections between 2010 and 2015 at all primary care clinics were obtained from the Korean Health Insurance Review and Assessment Service. The monthly detection rates of respiratory viruses, including adenovirus, respiratory syncytial virus, influenza virus, human coronavirus, and human rhinovirus, were collected from Korea Centers for Disease Control and Prevention. Cross-correlation analysis was conducted to quantify the temporal relationship between antibiotic use and respiratory virus activities as well as respiratory infections in primary clinics. RESULTS: The monthly use of different classes of antibiotic, including penicillins, other beta-lactam antibacterials, macrolides and quinolones, was significantly correlated with influenza virus activity. These correlations peaked at the 0-month lag with cross-correlation coefficients of 0.45 (p < 0.01), 0.46 (p < 0.01), 0.40 (p < 0.01), and 0.35 (< 0.01), respectively. Furthermore, a significant correlation was found between acute bronchitis and antibiotics, including penicillin (0.73, p < 0.01), macrolides (0.74, p < 0.01), and quinolones (0.45, p < 0.01), at the 0-month lag. CONCLUSIONS: Our findings suggest that there is a significant temporal relationship between influenza virus activity and antibiotic use in primary clinics. This relationship indicates that interventions aimed at reducing influenza cases in addition to effort to discourage the prescription of antibiotics by physicians may help to decrease unnecessary antibiotic consumption.",2018 Apr 25,"['Ryu, Sukhyun', 'Kim, Sojung', 'Kim, Bryan I.', 'Klein, Eili Y.', 'Yoon, Young Kyung', 'Chun, Byung Chul']",Antimicrob Resist Infect Control,,,True
c45cc3b97767ed8a1da4014f453533d6e840a3b6,PMC,Alpha/Beta Interferon (IFN-α/β) Signaling in Astrocytes Mediates Protection against Viral Encephalomyelitis and Regulates IFN-γ-Dependent Responses,http://dx.doi.org/10.1128/JVI.01901-17,PMC5923078,29491163,CC BY,"The contribution of distinct central nervous system (CNS) resident cells to protective alpha/beta interferon (IFN-α/β) function following viral infections is poorly understood. Based on numerous immune regulatory functions of astrocytes, we evaluated the contribution of astrocyte IFN-α/β signaling toward protection against the nonlethal glia- and neuronotropic mouse hepatitis virus (MHV) strain A59. Analysis of gene expression associated with IFN-α/β function, e.g., pattern recognition receptors (PRRs) and interferon-stimulated genes (ISGs), revealed lower basal mRNA levels in brain-derived astrocytes than in microglia. Although astrocytes poorly induced Ifnβ mRNA following infection, they upregulated various mRNAs in the IFN-α/β pathway to a higher extent than microglia, supporting effective IFN-α/β responsiveness. Ablation of the IFN-α/β receptor (IFNAR) in astrocytes using mGFAPcre IFNAR(fl/fl) mice resulted in severe encephalomyelitis and mortality, coincident with uncontrolled virus replication. Further, virus spread was not restricted to astrocytes but also affected microglia and neurons, despite increased and sustained Ifnα/β and ISG mRNA levels within the CNS. IFN-γ, a crucial mediator for MHV control, was not impaired in infected mGFAPcre IFNAR(fl/fl) mice despite reduced T cell CNS infiltration. Unexpectedly however, poor induction of IFN-γ-dependent major histocompatibility complex (MHC) class II expression on microglia supported that defective IFN-γ signaling contributes to uncontrolled virus replication. A link between sustained elevated IFN-α/β and impaired responsiveness to IFN-γ supports the novel concept that temporally limited early IFN-α/β responses are critical for effective antiviral IFN-γ function. Overall, our results imply that IFN-α/β signaling in astrocytes is not only critical in limiting early CNS viral spread but also promotes protective antiviral IFN-γ function. IMPORTANCE An antiviral state established by IFN-α/β contains initial viral spread as adaptive immunity develops. While it is apparent that the CNS lacks professional IFN-α/β producers and that resident cells have distinct abilities to elicit innate IFN-α/β responses, protective interactions between inducer and responder cells require further investigation. Infection with a glia- and neuronotropic coronavirus demonstrates that astrocytes mount a delayed but more robust response to infection than microglia, despite their lower basal mRNA levels of IFN-α/β-inducing components. Lethal, uncontrolled viral dissemination following ablation of astrocyte IFN-α/β signaling revealed the importance of IFN-α/β responses in a single cell type for protection. Sustained global IFN-α/β expression associated with uncontrolled virus did not suffice to protect neurons and further impaired responsiveness to protective IFN-γ. The results support astrocytes as critical contributors to innate immunity and the concept that limited IFN-α/β responses are critical for effective subsequent antiviral IFN-γ function.",2018 Apr 27,"['Hwang, Mihyun', 'Bergmann, Cornelia C.']",J Virol,,,True
23d0912618dac2c7b303fb41d0a83ba56023dc0c,PMC,A Plasma Biomarker Panel of Four MicroRNAs for the Diagnosis of Prostate Cancer,http://dx.doi.org/10.1038/s41598-018-24424-w,PMC5923293,29703916,CC BY,"Prostate cancer is diagnosed in over 1 million men every year globally, yet current diagnostic modalities are inadequate for identification of significant cancer and more reliable early diagnostic biomarkers are necessary for improved clinical management of prostate cancer patients. MicroRNAs (miRNAs) modulate important cellular processes/pathways contributing to cancer and are stably present in body fluids. In this study we profiled 372 cancer-associated miRNAs in plasma collected before (~60% patients) and after/during commencement of treatment (~40% patients), from age-matched prostate cancer patients and healthy controls, and observed elevated levels of 4 miRNAs - miR-4289, miR-326, miR-152-3p and miR-98-5p, which were validated in an independent cohort. The miRNA panel was able to differentiate between prostate cancer patients and controls (AUC = 0.88). Analysis of published miRNA transcriptomic data from clinical samples demonstrated low expression of miR-152-3p in tumour compared to adjacent non-malignant tissues. Overexpression of miR-152-3p increased proliferation and migration of prostate cancer cells, suggesting a role for this miRNA in prostate cancer pathogenesis, a concept that was supported by pathway analysis of predicted miR-152-3p target genes. In summary, a four miRNA panel, including miR-152-3p which likely targets genes with key roles in prostate cancer pathogenesis, has the potential to improve early prostate cancer diagnosis.",2018 Apr 27,"['Matin, Farhana', 'Jeet, Varinder', 'Moya, Leire', 'Selth, Luke A.', 'Chambers, Suzanne', None, 'Clements, Judith A.', 'Batra, Jyotsna']",Sci Rep,,,False
247d7378386c4c48cf327c151a9ea73040df0403,PMC,A Plasma Biomarker Panel of Four MicroRNAs for the Diagnosis of Prostate Cancer,http://dx.doi.org/10.1038/s41598-018-24424-w,PMC5923293,29703916,CC BY,"Prostate cancer is diagnosed in over 1 million men every year globally, yet current diagnostic modalities are inadequate for identification of significant cancer and more reliable early diagnostic biomarkers are necessary for improved clinical management of prostate cancer patients. MicroRNAs (miRNAs) modulate important cellular processes/pathways contributing to cancer and are stably present in body fluids. In this study we profiled 372 cancer-associated miRNAs in plasma collected before (~60% patients) and after/during commencement of treatment (~40% patients), from age-matched prostate cancer patients and healthy controls, and observed elevated levels of 4 miRNAs - miR-4289, miR-326, miR-152-3p and miR-98-5p, which were validated in an independent cohort. The miRNA panel was able to differentiate between prostate cancer patients and controls (AUC = 0.88). Analysis of published miRNA transcriptomic data from clinical samples demonstrated low expression of miR-152-3p in tumour compared to adjacent non-malignant tissues. Overexpression of miR-152-3p increased proliferation and migration of prostate cancer cells, suggesting a role for this miRNA in prostate cancer pathogenesis, a concept that was supported by pathway analysis of predicted miR-152-3p target genes. In summary, a four miRNA panel, including miR-152-3p which likely targets genes with key roles in prostate cancer pathogenesis, has the potential to improve early prostate cancer diagnosis.",2018 Apr 27,"['Matin, Farhana', 'Jeet, Varinder', 'Moya, Leire', 'Selth, Luke A.', 'Chambers, Suzanne', None, 'Clements, Judith A.', 'Batra, Jyotsna']",Sci Rep,,,True
d9d1928e12dca038ff13cd0188d9fdc10a0f560d,PMC,New Insights from Elucidating the Role of LMP1 in Nasopharyngeal Carcinoma,http://dx.doi.org/10.3390/cancers10040086,PMC5923341,29561768,CC BY,"Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV) oncogenic protein that has no intrinsic enzymatic activity or sequence homology to cellular or viral proteins. The oncogenic potential of LMP1 has been ascribed to pleiotropic signaling properties initiated through protein-protein interactions in cytosolic membrane compartments, but the effects of LMP1 extend to nuclear and extracellular processes. Although LMP1 is one of the latent genes required for EBV-immortalization of B cells, the biology of LMP1 in the pathogenesis of the epithelial cancer nasopharyngeal carcinoma (NPC) is more complex. NPC is prevalent in specific regions of the world with high incidence in southeast China. The epidemiology and time interval from seroconversion to NPC onset in adults would suggest the involvement of multiple risk factors that complement the establishment of a latent and persistent EBV infection. The contribution of LMP1 to EBV pathogenesis in polarized epithelia has only recently begun to be elucidated. Furthermore, the LMP1 gene has emerged as one of the most divergent sequences in the EBV genome. This review will discuss the significance of recent advances in NPC research from elucidating LMP1 function in epithelial cells and lessons that could be learned from mining LMP1 sequence diversity.",2018 Mar 21,"['Shair, Kathy H. Y.', 'Reddy, Akhil', 'Cooper, Vaughn S.']",Cancers (Basel),,,True
187607fca4b1dc4e30fe91d36520432aec36f795,PMC,Rapid Viral Diagnosis of Orthopoxviruses by Electron Microscopy: Optional or a Must?,http://dx.doi.org/10.3390/v10040142,PMC5923436,29565285,CC BY,"Diagnostic electron microscopy (DEM) was an essential component of viral diagnosis until the development of highly sensitive nucleic acid amplification techniques (NAT). The simple negative staining technique of DEM was applied widely to smallpox diagnosis until the world-wide eradication of the human-specific pathogen in 1980. Since then, the threat of smallpox re-emerging through laboratory escape, molecular manipulation, synthetic biology or bioterrorism has not totally disappeared and would be a major problem in an unvaccinated population. Other animal poxviruses may also emerge as human pathogens. With its rapid results (only a few minutes after arrival of the specimen), no requirement for specific reagents and its “open view”, DEM remains an important component of virus diagnosis, particularly because it can easily and reliably distinguish smallpox virus or any other member of the orthopoxvirus (OPV) genus from parapoxviruses (PPV) and the far more common and less serious herpesviruses (herpes simplex and varicella zoster). Preparation, enrichment, examination, internal standards and suitable organisations are discussed to make clear its continuing value as a diagnostic technique.",2018 Mar 22,"['Gelderblom, Hans R.', 'Madeley, Dick']",Viruses,,,True
aea827ad6b4888677fad2702e41ef2b6d65e8141,PMC,Inhibition of Zika Virus Replication by Silvestrol,http://dx.doi.org/10.3390/v10040149,PMC5923443,29584632,CC BY,"The Zika virus (ZIKV) outbreak in 2016 in South America with specific pathogenic outcomes highlighted the need for new antiviral substances with broad-spectrum activities to react quickly to unexpected outbreaks of emerging viral pathogens. Very recently, the natural compound silvestrol isolated from the plant Aglaia foveolata was found to have very potent antiviral effects against the (−)-strand RNA-virus Ebola virus as well as against Corona- and Picornaviruses with a (+)-strand RNA-genome. This antiviral activity is based on the impaired translation of viral RNA by the inhibition of the DEAD-box RNA helicase eukaryotic initiation factor-4A (eIF4A) which is required to unwind structured 5´-untranslated regions (5′-UTRs) of several proto-oncogenes and thereby facilitate their translation. Zika virus is a flavivirus with a positive-stranded RNA-genome harboring a 5′-capped UTR with distinct secondary structure elements. Therefore, we investigated the effects of silvestrol on ZIKV replication in A549 cells and primary human hepatocytes. Two different ZIKV strains were used. In both infected A549 cells and primary human hepatocytes, silvestrol has the potential to exert a significant inhibition of ZIKV replication for both analyzed strains, even though the ancestor strain from Uganda is less sensitive to silvestrol. Our data might contribute to identify host factors involved in the control of ZIKV infection and help to develop antiviral concepts that can be used to treat a variety of viral infections without the risk of resistances because a host protein is targeted.",2018 Mar 27,"['Elgner, Fabian', 'Sabino, Catarina', 'Basic, Michael', 'Ploen, Daniela', 'Grünweller, Arnold', 'Hildt, Eberhard']",Viruses,,,True
8696a05757f7baa10ec489f06252aa93884ba2eb,PMC,Inhibition of Zika Virus Replication by Silvestrol,http://dx.doi.org/10.3390/v10040149,PMC5923443,29584632,CC BY,"The Zika virus (ZIKV) outbreak in 2016 in South America with specific pathogenic outcomes highlighted the need for new antiviral substances with broad-spectrum activities to react quickly to unexpected outbreaks of emerging viral pathogens. Very recently, the natural compound silvestrol isolated from the plant Aglaia foveolata was found to have very potent antiviral effects against the (−)-strand RNA-virus Ebola virus as well as against Corona- and Picornaviruses with a (+)-strand RNA-genome. This antiviral activity is based on the impaired translation of viral RNA by the inhibition of the DEAD-box RNA helicase eukaryotic initiation factor-4A (eIF4A) which is required to unwind structured 5´-untranslated regions (5′-UTRs) of several proto-oncogenes and thereby facilitate their translation. Zika virus is a flavivirus with a positive-stranded RNA-genome harboring a 5′-capped UTR with distinct secondary structure elements. Therefore, we investigated the effects of silvestrol on ZIKV replication in A549 cells and primary human hepatocytes. Two different ZIKV strains were used. In both infected A549 cells and primary human hepatocytes, silvestrol has the potential to exert a significant inhibition of ZIKV replication for both analyzed strains, even though the ancestor strain from Uganda is less sensitive to silvestrol. Our data might contribute to identify host factors involved in the control of ZIKV infection and help to develop antiviral concepts that can be used to treat a variety of viral infections without the risk of resistances because a host protein is targeted.",2018 Mar 27,"['Elgner, Fabian', 'Sabino, Catarina', 'Basic, Michael', 'Ploen, Daniela', 'Grünweller, Arnold', 'Hildt, Eberhard']",Viruses,,,False
b47b54d0d0a92245735b5b88ed1c3634574772d5,PMC,Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor,http://dx.doi.org/10.3390/v10040152,PMC5923446,29584652,CC BY,"The recent 2014–2016 West African Ebola virus epidemic underscores the need for the development of novel anti-Ebola therapeutics, due to the high mortality rates of Ebola virus infections and the lack of FDA-approved vaccine or therapy that is available for the prevention and treatment. Traditional Chinese medicines (TCMs) represent a huge reservoir of bioactive chemicals and many TCMs have been shown to have antiviral activities. 373 extracts from 128 TCMs were evaluated using a high throughput assay to screen for inhibitors of Ebola virus cell entry. Extract of Rhodiola rosea displayed specific and potent inhibition against cell entry of both Ebola virus and Marburg virus. In addition, twenty commercial compounds that were isolated from Rhodiola rosea were evaluated using the pseudotyped Ebola virus entry assay, and it was found that ellagic acid and gallic acid, which are two structurally related compounds, are the most effective ones. The activity of the extract and the two pure compounds were validated using infectious Ebola virus. The time-of-addition experiments suggest that, mechanistically, the Rhodiola rosea extract and the effective compounds act at an early step in the infection cycle following initial cell attachment, but prior to viral/cell membrane fusion. Our findings provide evidence that Rhodiola rosea has potent anti-filovirus properties that may be developed as a novel anti-Ebola treatment.",2018 Mar 27,"['Cui, Qinghua', 'Du, Ruikun', 'Anantpadma, Manu', 'Schafer, Adam', 'Hou, Lin', 'Tian, Jingzhen', 'Davey, Robert A.', 'Cheng, Han', 'Rong, Lijun']",Viruses,,,True
9baa795737131065dbfb81e29a82e1aad8f37690,PMC,Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor,http://dx.doi.org/10.3390/v10040152,PMC5923446,29584652,CC BY,"The recent 2014–2016 West African Ebola virus epidemic underscores the need for the development of novel anti-Ebola therapeutics, due to the high mortality rates of Ebola virus infections and the lack of FDA-approved vaccine or therapy that is available for the prevention and treatment. Traditional Chinese medicines (TCMs) represent a huge reservoir of bioactive chemicals and many TCMs have been shown to have antiviral activities. 373 extracts from 128 TCMs were evaluated using a high throughput assay to screen for inhibitors of Ebola virus cell entry. Extract of Rhodiola rosea displayed specific and potent inhibition against cell entry of both Ebola virus and Marburg virus. In addition, twenty commercial compounds that were isolated from Rhodiola rosea were evaluated using the pseudotyped Ebola virus entry assay, and it was found that ellagic acid and gallic acid, which are two structurally related compounds, are the most effective ones. The activity of the extract and the two pure compounds were validated using infectious Ebola virus. The time-of-addition experiments suggest that, mechanistically, the Rhodiola rosea extract and the effective compounds act at an early step in the infection cycle following initial cell attachment, but prior to viral/cell membrane fusion. Our findings provide evidence that Rhodiola rosea has potent anti-filovirus properties that may be developed as a novel anti-Ebola treatment.",2018 Mar 27,"['Cui, Qinghua', 'Du, Ruikun', 'Anantpadma, Manu', 'Schafer, Adam', 'Hou, Lin', 'Tian, Jingzhen', 'Davey, Robert A.', 'Cheng, Han', 'Rong, Lijun']",Viruses,,,False
af7e42cdc9fa098ffcfdbf92ebfb9dbd4dbde545,PMC,"Imaging, Tracking and Computational Analyses of Virus Entry and Egress with the Cytoskeleton",http://dx.doi.org/10.3390/v10040166,PMC5923460,29614729,CC BY,"Viruses have a dual nature: particles are “passive substances” lacking chemical energy transformation, whereas infected cells are “active substances” turning-over energy. How passive viral substances convert to active substances, comprising viral replication and assembly compartments has been of intense interest to virologists, cell and molecular biologists and immunologists. Infection starts with virus entry into a susceptible cell and delivers the viral genome to the replication site. This is a multi-step process, and involves the cytoskeleton and associated motor proteins. Likewise, the egress of progeny virus particles from the replication site to the extracellular space is enhanced by the cytoskeleton and associated motor proteins. This overcomes the limitation of thermal diffusion, and transports virions and virion components, often in association with cellular organelles. This review explores how the analysis of viral trajectories informs about mechanisms of infection. We discuss the methodology enabling researchers to visualize single virions in cells by fluorescence imaging and tracking. Virus visualization and tracking are increasingly enhanced by computational analyses of virus trajectories as well as in silico modeling. Combined approaches reveal previously unrecognized features of virus-infected cells. Using select examples of complementary methodology, we highlight the role of actin filaments and microtubules, and their associated motors in virus infections. In-depth studies of single virion dynamics at high temporal and spatial resolutions thereby provide deep insight into virus infection processes, and are a basis for uncovering underlying mechanisms of how cells function.",2018 Mar 31,"['Wang, I-Hsuan', 'Burckhardt, Christoph J.', 'Yakimovich, Artur', 'Greber, Urs F.']",Viruses,,,True
8e0621d9c791cda1b772290d37ab245bf7023514,PMC,Arbidol (Umifenovir): A Broad-Spectrum Antiviral Drug That Inhibits Medically Important Arthropod-Borne Flaviviruses,http://dx.doi.org/10.3390/v10040184,PMC5923478,29642580,CC BY,"Arthropod-borne flaviviruses are human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy has currently been reported. Arbidol (umifenovir) is a broad-spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound shows activities against numerous DNA and RNA viruses. The mode of action is based predominantly on impairment of critical steps in virus-cell interactions. Here we demonstrate that arbidol possesses micromolar-level anti-viral effects (EC(50) values ranging from 10.57 ± 0.74 to 19.16 ± 0.29 µM) in Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis virus, three medically important representatives of the arthropod-borne flaviviruses. Interestingly, no antiviral effects of arbidol are observed in virus infected porcine stable kidney cells (PS), human neuroblastoma cells (UKF-NB-4), and human hepatoma cells (Huh-7 cells) indicating that the antiviral effect of arbidol is strongly cell-type dependent. Arbidol shows increasing cytotoxicity when tested in various cell lines, in the order: Huh-7 < HBCA < PS < UKF-NB-4 < Vero with CC(50) values ranging from 18.69 ± 0.1 to 89.72 ± 0.19 µM. Antiviral activities and acceptable cytotoxicity profiles suggest that arbidol could be a promising candidate for further investigation as a potential therapeutic agent in selective treatment of flaviviral infections.",2018 Apr 10,"['Haviernik, Jan', 'Štefánik, Michal', 'Fojtíková, Martina', 'Kali, Sabrina', 'Tordo, Noël', 'Rudolf, Ivo', 'Hubálek, Zdeněk', 'Eyer, Luděk', 'Ruzek, Daniel']",Viruses,,,True
f489bc214786cc253c014ae8e42d1c7e0c590138,PMC,Arbidol (Umifenovir): A Broad-Spectrum Antiviral Drug That Inhibits Medically Important Arthropod-Borne Flaviviruses,http://dx.doi.org/10.3390/v10040184,PMC5923478,29642580,CC BY,"Arthropod-borne flaviviruses are human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy has currently been reported. Arbidol (umifenovir) is a broad-spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound shows activities against numerous DNA and RNA viruses. The mode of action is based predominantly on impairment of critical steps in virus-cell interactions. Here we demonstrate that arbidol possesses micromolar-level anti-viral effects (EC(50) values ranging from 10.57 ± 0.74 to 19.16 ± 0.29 µM) in Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis virus, three medically important representatives of the arthropod-borne flaviviruses. Interestingly, no antiviral effects of arbidol are observed in virus infected porcine stable kidney cells (PS), human neuroblastoma cells (UKF-NB-4), and human hepatoma cells (Huh-7 cells) indicating that the antiviral effect of arbidol is strongly cell-type dependent. Arbidol shows increasing cytotoxicity when tested in various cell lines, in the order: Huh-7 < HBCA < PS < UKF-NB-4 < Vero with CC(50) values ranging from 18.69 ± 0.1 to 89.72 ± 0.19 µM. Antiviral activities and acceptable cytotoxicity profiles suggest that arbidol could be a promising candidate for further investigation as a potential therapeutic agent in selective treatment of flaviviral infections.",2018 Apr 10,"['Haviernik, Jan', 'Štefánik, Michal', 'Fojtíková, Martina', 'Kali, Sabrina', 'Tordo, Noël', 'Rudolf, Ivo', 'Hubálek, Zdeněk', 'Eyer, Luděk', 'Ruzek, Daniel']",Viruses,,,False
369914e87f682579eb3a5efeb43dc0184a88b5d6,PMC,Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication,http://dx.doi.org/10.3390/v10040191,PMC5923485,29652799,CC BY,"Viruses must parasitize host cell translational machinery in order to make proteins for viral progeny. In this study, we sought to use this signal transduction conduit against them by inhibiting multiple kinases that influence translation. Previous work indicated that several kinases involved in translation, including p70 S6K, p90RSK, ERK, and p38 MAPK, are phosphorylated following Rift Valley fever virus (RVFV) infection. Furthermore, inhibiting p70 S6K through treatment with the FDA approved drug rapamycin prevents RVFV pathogenesis in a mouse model of infection. We hypothesized that inhibiting either p70 S6K, p90RSK, or p90RSK’s upstream kinases, ERK and p38 MAPK, would decrease translation and subsequent viral replication. Treatment with the p70 S6K inhibitor PF-4708671 resulted in decreased phosphorylation of translational proteins and reduced RVFV titers. In contrast, treatment with the p90RSK inhibitor BI-D1870, p38MAPK inhibitor SB203580, or the ERK inhibitor PD0325901 alone had minimal influence on RVFV titers. The combination of PF-4708671 and BI-D1870 treatment resulted in robust inhibition of RVFV replication. Likewise, a synergistic inhibition of RVFV replication was observed with p38MAPK inhibitor SB203580 or the ERK inhibitor PD0325901 combined with rapamycin treatment. These findings serve as a proof of concept regarding combination kinase inhibitor treatment for RVFV infection.",2018 Apr 13,"['Bell, Todd M.', 'Espina, Virginia', 'Lundberg, Lindsay', 'Pinkham, Chelsea', 'Brahms, Ashwini', 'Carey, Brian D.', 'Lin, Shih-Chao', 'Dahal, Bibha', 'Woodson, Caitlin', 'de la Fuente, Cynthia', 'Liotta, Lance A.', 'Bailey, Charles L.', 'Kehn-Hall, Kylene']",Viruses,,,True
2769723b9b497b45c8178f8f68dc48a5fed06db6,PMC,Full-Genome Characterization and Genetic Evolution of West African Isolates of Bagaza Virus,http://dx.doi.org/10.3390/v10040193,PMC5923487,29652824,CC BY,"Bagaza virus is a mosquito-borne flavivirus, first isolated in 1966 in Central African Republic. It has currently been identified in mosquito pools collected in the field in West and Central Africa. Emergence in wild birds in Europe and serological evidence in encephalitis patients in India raise questions on its genetic evolution and the diversity of isolates circulating in Africa. To better understand genetic diversity and evolution of Bagaza virus, we describe the full-genome characterization of 11 West African isolates, sampled from 1988 to 2014. Parameters such as genetic distances, N-glycosylation patterns, recombination events, selective pressures, and its codon adaptation to human genes are assessed. Our study is noteworthy for the observation of N-glycosylation and recombination in Bagaza virus and provides insight into its Indian origin from the 13th century. Interestingly, evidence of Bagaza virus codon adaptation to human house-keeping genes is also observed to be higher than those of other flaviviruses well known in human infections. Genetic variations on genome of West African Bagaza virus could play an important role in generating diversity and may promote Bagaza virus adaptation to other vertebrates and become an important threat in human health.",2018 Apr 13,"['Faye, Martin', 'Faye, Oumar', 'Diagne, Moussa Moise', 'Fall, Gamou', 'Weidmann, Manfred', 'Sembene, Mbacke', 'Sall, Amadou Alpha', 'Faye, Ousmane']",Viruses,,,True
497a6c713428123479a545654549ab88457ed9d7,PMC,Full-Genome Characterization and Genetic Evolution of West African Isolates of Bagaza Virus,http://dx.doi.org/10.3390/v10040193,PMC5923487,29652824,CC BY,"Bagaza virus is a mosquito-borne flavivirus, first isolated in 1966 in Central African Republic. It has currently been identified in mosquito pools collected in the field in West and Central Africa. Emergence in wild birds in Europe and serological evidence in encephalitis patients in India raise questions on its genetic evolution and the diversity of isolates circulating in Africa. To better understand genetic diversity and evolution of Bagaza virus, we describe the full-genome characterization of 11 West African isolates, sampled from 1988 to 2014. Parameters such as genetic distances, N-glycosylation patterns, recombination events, selective pressures, and its codon adaptation to human genes are assessed. Our study is noteworthy for the observation of N-glycosylation and recombination in Bagaza virus and provides insight into its Indian origin from the 13th century. Interestingly, evidence of Bagaza virus codon adaptation to human house-keeping genes is also observed to be higher than those of other flaviviruses well known in human infections. Genetic variations on genome of West African Bagaza virus could play an important role in generating diversity and may promote Bagaza virus adaptation to other vertebrates and become an important threat in human health.",2018 Apr 13,"['Faye, Martin', 'Faye, Oumar', 'Diagne, Moussa Moise', 'Fall, Gamou', 'Weidmann, Manfred', 'Sembene, Mbacke', 'Sall, Amadou Alpha', 'Faye, Ousmane']",Viruses,,,False
3fc9f794eaab19c5355f54fee069feaedf8d752a,PMC,Interferon Independent Non-Canonical STAT Activation and Virus Induced Inflammation,http://dx.doi.org/10.3390/v10040196,PMC5923490,29662014,CC BY,"Interferons (IFNs) are a group of secreted proteins that play critical roles in antiviral immunity, antitumor activity, activation of cytotoxic T cells, and modulation of host immune responses. IFNs are cytokines, and bind receptors on cell surfaces to trigger signal transduction. The major signaling pathway activated by IFNs is the JAK/STAT (Janus kinase/signal transducer and activator of transcription) pathway, a complex pathway involved in both viral and host survival strategies. On the one hand, viruses have evolved strategies to escape from antiviral host defenses evoked by IFN-activated JAK/STAT signaling. On the other hand, viruses have also evolved to exploit the JAK/STAT pathway to evoke activation of certain STATs that somehow promote viral pathogenesis. In this review, recent progress in our understanding of the virus-induced IFN-independent STAT signaling and its potential roles in viral induced inflammation and pathogenesis are summarized in detail, and perspectives are provided.",2018 Apr 14,"['Nan, Yuchen', 'Wu, Chunyan', 'Zhang, Yan-Jin']",Viruses,,,True
b0e519e2224e5ee8dd2303ed3f347e049cb599a2,PMC,The Hard Way towards an Antibody-Based HIV-1 Env Vaccine: Lessons from Other Viruses,http://dx.doi.org/10.3390/v10040197,PMC5923491,29662026,CC BY,"Although effective antibody-based vaccines have been developed against multiple viruses, such approaches have so far failed for the human immunodeficiency virus type 1 (HIV-1). Despite the success of anti-retroviral therapy (ART) that has turned HIV-1 infection into a chronic disease and has reduced the number of new infections worldwide, a vaccine against HIV-1 is still urgently needed. We discuss here the major reasons for the failure of “classical” vaccine approaches, which are mostly due to the biological properties of the virus itself. HIV-1 has developed multiple mechanisms of immune escape, which also account for vaccine failure. So far, no vaccine candidate has been able to induce broadly neutralizing antibodies (bnAbs) against primary patient viruses from different clades. However, such antibodies were identified in a subset of patients during chronic infection and were shown to protect from infection in animal models and to reduce viremia in first clinical trials. Their detailed characterization has guided structure-based reverse vaccinology approaches to design better HIV-1 envelope (Env) immunogens. Furthermore, conserved Env epitopes have been identified, which are promising candidates in view of clinical applications. Together with new vector-based technologies, considerable progress has been achieved in recent years towards the development of an effective antibody-based HIV-1 vaccine.",2018 Apr 15,"['Ringel, Oliver', 'Vieillard, Vincent', 'Debré, Patrice', 'Eichler, Jutta', 'Büning, Hildegard', 'Dietrich, Ursula']",Viruses,,,True
c5c2bc7a07670d6fb970d84a59aab3832752a3f1,PMC,Role of the ERK1/2 Signaling Pathway in the Replication of Junín and Tacaribe Viruses,http://dx.doi.org/10.3390/v10040199,PMC5923493,29673133,CC BY,"We have previously shown that the infection of cell cultures with the arenaviruses Junín (JUNV), Tacaribe (TCRV), and Pichindé promotes the phosphorylation of mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinases 1 and 2 (ERK1/2) and that this activation is required for the achievement of a productive infection. Here we examined the contribution of ERK1/2 in early steps of JUNV and TCRV multiplication. JUNV adsorption, internalization, and uncoating were not affected by treatment of cultured cells with U0126, an inhibitor of the ERK1/2 signaling pathway. In contrast, U0126 caused a marked reduction in viral protein expression and RNA synthesis, while JUNV RNA synthesis was significantly augmented in the presence of an activator of the ERK1/2 pathway. Moreover, U0126 impaired the expression of a reporter gene in a TCRV-based replicon system, confirming the ability of the compound to hinder arenavirus macromolecular synthesis. By using a cell-based assay, we determined that the inhibitor did not affect the translation of a synthetic TCRV-like mRNA. No changes in the phosphorylation pattern of the translation factor eIF2α were found in U0126-treated cells. Our results indicate that U0126 impairs viral RNA synthesis, thereby leading to a subsequent reduction in viral protein expression. Thus, we conclude that ERK1/2 signaling activation is required for an efficient arenavirus RNA synthesis.",2018 Apr 17,"['Brunetti, Jesús E.', 'Foscaldi, Sabrina', 'Quintana, Verónica M.', 'Scolaro, Luis A.', 'López, Nora', 'Castilla, Viviana']",Viruses,,,True
e10083014ab2d0c09bd8bed432e8ca883d8d3431,PMC,CD81 Receptor Regions outside the Large Extracellular Loop Determine Hepatitis C Virus Entry into Hepatoma Cells,http://dx.doi.org/10.3390/v10040207,PMC5923501,29677132,CC BY,"Hepatitis C virus (HCV) enters human hepatocytes using four essential entry factors, one of which is human CD81 (hCD81). The tetraspanin hCD81 contains a large extracellular loop (LEL), which interacts with the E2 glycoprotein of HCV. The role of the non-LEL regions of hCD81 (intracellular tails, four transmembrane domains, small extracellular loop and intracellular loop) is poorly understood. Here, we studied the contribution of these domains to HCV susceptibility of hepatoma cells by generating chimeras of related tetraspanins with the hCD81 LEL. Our results show that non-LEL regions in addition to the LEL determine susceptibility of cells to HCV. While closely related tetraspanins (X. tropicalis CD81 and D. rerio CD81) functionally complement hCD81 non-LEL regions, distantly related tetraspanins (C. elegans TSP9 amd D. melanogaster TSP96F) do not and tetraspanins with intermediate homology (hCD9) show an intermediate phenotype. Tetraspanin homology and susceptibility to HCV correlate positively. For some chimeras, infectivity correlates with surface expression. In contrast, the hCD9 chimera is fully surface expressed, binds HCV E2 glycoprotein but is impaired in HCV receptor function. We demonstrate that a cholesterol-coordinating glutamate residue in CD81, which hCD9 lacks, promotes HCV infection. This work highlights the hCD81 non-LEL regions as additional HCV susceptibility-determining factors.",2018 Apr 20,"['Banse, Pia', 'Moeller, Rebecca', 'Bruening, Janina', 'Lasswitz, Lisa', 'Kahl, Sina', 'Khan, Abdul G.', 'Marcotrigiano, Joseph', 'Pietschmann, Thomas', 'Gerold, Gisa']",Viruses,,,True
f1e1e2511e051195c8327a56d5c311a2dd4ab6b3,PMC,Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity,http://dx.doi.org/10.3390/v10040211,PMC5923505,29677162,CC BY,"Nucleoside analogs have been frequently identified as antiviral agents. In recent years, gemcitabine, a cytidine analog in clinical use for the treatment of many solid tumors, was also shown to have antiviral activity against a broad range of viruses. Nucleoside analogs generally interfere with cellular nucleos(t)ide synthesis pathways, resulting in the depletion or imbalance of (d)NTP pools. Intriguingly, a few recent reports have shown that some nucleoside analogs, including gemcitabine, activated innate immunity, inducing the expression of interferon-stimulated genes, through nucleos(t)ide synthesis inhibition. The precise crosstalk between these two independent processes remains to be determined. Nonetheless, we summarize the current knowledge of nucleos(t)ide synthesis inhibition-related innate immunity and propose it as a newly emerging antiviral mechanism of nucleoside analogs.",2018 Apr 20,"['Shin, Hye Jin', 'Kim, Chonsaeng', 'Cho, Sungchan']",Viruses,,,True
03b35e72b8abfe6c88da27e72b5ecc8e77211dd2,PMC,"Comparison of the fecal microbiota of domestic commercial meat, laboratory, companion, and shelter rabbits (Oryctolagus cuniculi)",http://dx.doi.org/10.1186/s12917-018-1464-6,PMC5924505,29703196,CC BY,"BACKGROUND: Rabbits are cecotrophic, hindgut-fermenters that rely heavily on their gastrointestinal microbiota for optimal digestion of plant-based diets. Dysbiosis, caused by disruption of the gastrointestinal microbiota, is known to predispose rabbits to rabbit enteritis complex (REC), a major cause of morbidity and mortality. The objectives of this study were to describe the fecal microbiota of domestic rabbits from a variety of settings (commercial meat, companion, laboratory, and shelter) and to identify how factors such as age, season, and routine antimicrobial use affect the fecal microbiota composition. RESULTS: A total of 86 pooled commercial meat, 54 companion, 14 pooled laboratory, and 14 shelter rabbit fecal samples were evaluated using 16S rRNA gene sequencing of the V4 region. In all sample types, the predominant bacterial phylum was Firmicutes. Other commonly identified phyla (composing ≥ 1% of the total microbiota composition) were Verrucomicrobia, Proteobacteria, and Bacteroidetes. Significant differences in composition were noted between commercial, companion, laboratory, and shelter rabbit samples for proportions of Verrucomicrobia (P < 0.01), Proteobacteria (P < 0.01), and Lentisphaerae (P = 0.01) within the total microbiota. Within the commercial meat rabbit samples, significant differences between the microbiota composition of growers (n = 42) and does (n = 44) were limited to one unclassified Firmicutes (P = 0.03) and no differences were identified at the phylum level. Significant differences were present between fecal samples taken from rabbits during the summer (n = 44) compared to the winter (n = 42), with Firmicutes (P = 0.04), Verrucomicrobia (P = 0.03), Proteobacteria (P = 0.02), Deinococcus-Thermus (P = 0.04), Armatimonadates (P = 0.003), and Actinobacteria (P = 0.03) forming significantly different proportions of the microbiota. The only significant difference in composition between those farms that routinely reported antimicrobial use and those that did not was in one unclassified Bacteroidetes (P < 0.05) and no differences were identified at the phylum level. CONCLUSIONS: Rabbit husbandry and diet, in addition to season, significantly influence the fecal microbiota composition of domestic rabbits, while age of the rabbit post-weaning has minimal impact. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1464-6) contains supplementary material, which is available to authorized users.",2018 Apr 27,"['Kylie, Jennifer', 'Weese, J. Scott', 'Turner, Patricia V.']",BMC Vet Res,,,True
b46170b59d879a53ec59e8a24a0c01b16df08e3d,PMC,Gene Therapy for Chronic HBV—Can We Eliminate cccDNA?,http://dx.doi.org/10.3390/genes9040207,PMC5924549,29649127,CC BY,"Chronic infection with the hepatitis B virus (HBV) is a global health concern and accounts for approximately 1 million deaths annually. Amongst other limitations of current anti-HBV treatment, failure to eliminate the viral covalently closed circular DNA (cccDNA) and emergence of resistance remain the most worrisome. Viral rebound from latent episomal cccDNA reservoirs occurs following cessation of therapy, patient non-compliance, or the development of escape mutants. Simultaneous viral co-infections, such as by HIV-1, further complicate therapeutic interventions. These challenges have prompted development of novel targeted hepatitis B therapies. Given the ease with which highly specific and potent nucleic acid therapeutics can be rationally designed, gene therapy has generated interest for antiviral application. Gene therapy strategies developed for HBV include gene silencing by harnessing RNA interference, transcriptional inhibition through epigenetic modification of target DNA, genome editing by designer nucleases, and immune modulation with cytokines. DNA-binding domains and effectors based on the zinc finger (ZF), transcription activator-like effector (TALE), and clustered regularly interspaced short palindromic repeat (CRISPR) systems are remarkably well suited to targeting episomal cccDNA. This review discusses recent developments and challenges facing the field of anti-HBV gene therapy, its potential curative significance and the progress towards clinical application.",2018 Apr 12,"['Bloom, Kristie', 'Maepa, Mohube Betty', 'Ely, Abdullah', 'Arbuthnot, Patrick']",Genes (Basel),,,True
2585403015b1b1b31ab187eace93d67f4441e3cf,PMC,Overview of Virus Metagenomic Classification Methods and Their Biological Applications,http://dx.doi.org/10.3389/fmicb.2018.00749,PMC5924777,29740407,CC BY,"Metagenomics poses opportunities for clinical and public health virology applications by offering a way to assess complete taxonomic composition of a clinical sample in an unbiased way. However, the techniques required are complicated and analysis standards have yet to develop. This, together with the wealth of different tools and workflows that have been proposed, poses a barrier for new users. We evaluated 49 published computational classification workflows for virus metagenomics in a literature review. To this end, we described the methods of existing workflows by breaking them up into five general steps and assessed their ease-of-use and validation experiments. Performance scores of previous benchmarks were summarized and correlations between methods and performance were investigated. We indicate the potential suitability of the different workflows for (1) time-constrained diagnostics, (2) surveillance and outbreak source tracing, (3) detection of remote homologies (discovery), and (4) biodiversity studies. We provide two decision trees for virologists to help select a workflow for medical or biodiversity studies, as well as directions for future developments in clinical viral metagenomics.",2018 Apr 23,"['Nooij, Sam', 'Schmitz, Dennis', 'Vennema, Harry', 'Kroneman, Annelies', 'Koopmans, Marion P. G.']",Front Microbiol,,,True
a541d630fd5736ce515214386cf9642b1e3d02e7,PMC,The Highest Cited Papers in Brucellosis: Identification Using Two Databases and Review of the Papers' Major Findings,http://dx.doi.org/10.1155/2018/9291326,PMC5924997,29850587,CC BY,"Citation classics represent the highest impact work in a given field. We aim to identify and analyze the most frequently cited papers on brucellosis. We used the databases Scopus and Web of Science to determine the most frequently cited papers. The most cited fifty papers in each database were identified. We then ranked the papers according to the highest citation count recorded from any of the two databases. The most frequently cited paper received 964 citations and was by DelVecchio VG et al. reporting the complete genomic sequencing of Brucella melitensis. The papers were published in 30 journals led by the “Infection and Immunity” journal and the “Veterinary Microbiology” journal (each had 7 papers). Citation classics in brucellosis were all in English except one in French and were mostly of basic science type. In addition, we noticed that 12 articles that were identified among the highest fifty articles in one database were missed by the other database and vice versa. Therefore, we suggest that searching in more than one database would detect additional citation classics.",2018 Apr 11,"['Bakri, Faris Ghalib', 'AlQadiri, Hamzah M.', 'Adwan, Marwan Hmoud']",Biomed Res Int,,,True
b6ccfd5dcb8970df391aeaed0992cb00251fc7f1,PMC,A Rare Case of Human Coronavirus 229E Associated with Acute Respiratory Distress Syndrome in a Healthy Adult,http://dx.doi.org/10.1155/2018/6796839,PMC5925015,29850307,CC BY,"Human coronavirus 229E (HCoV-229E) is one of the first coronavirus strains being described. It is linked to common cold symptoms in healthy adults. Younger children and the elderly are considered vulnerable to developing lower respiratory tract infections (LRTIs). In particular, immunocompromised patients have been reported with severe and life-threatening LRTIs attributed to HCoV-229E. We report for the first time a case of LRTI and acute respiratory distress syndrome developed in a healthy adult with no comorbidities and HCoV-229E strain identified as the only causative agent. A 45-year-old female with a clear medical history presented with fever, cough, and headache. Respiratory tract infection was diagnosed, and empirical antibiotics were started. Within two days, she developed bilateral pleural effusions, diffuse consolidations, and ground glass opacities involving all lung fields. She needed immediate oxygen supply, while ABGs deteriorated and chest imaging and PaO(2)/FiO(2) indicated ARDS. Early administration of systemic corticosteroids led to gradual clinical improvement. Multiplex PCR from nasal secretions was positive only for HCoV-229E and negative for multiple other pathogens. It remains to be elucidated how an immunocompetent adult developed a life-threatening LRTI caused by a “benign considered” coronavirus strain, the HCoV-229E.",2018 Apr 15,"['Vassilara, Foula', 'Spyridaki, Aikaterini', 'Pothitos, George', 'Deliveliotou, Athanassia', 'Papadopoulos, Antonios']",Case Rep Infect Dis,,,True
207885268ef61365fc89820ecb7c854a3dc23d9a,PMC,A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A from binding to RNase L,http://dx.doi.org/10.1371/journal.ppat.1006989,PMC5927464,29652922,CC BY,"The OAS/RNase L pathway is one of the best-characterized effector pathways of the IFN antiviral response. It inhibits the replication of many viruses and ultimately promotes apoptosis of infected cells, contributing to the control of virus spread. However, viruses have evolved a range of escape strategies that act against different steps in the pathway. Here we unraveled a novel escape strategy involving Theiler’s murine encephalomyelitis virus (TMEV) L* protein. Previously we found that L* was the first viral protein binding directly RNase L. Our current data show that L* binds the ankyrin repeats R1 and R2 of RNase L and inhibits 2’-5’ oligoadenylates (2-5A) binding to RNase L. Thereby, L* prevents dimerization and oligomerization of RNase L in response to 2-5A. Using chimeric mouse hepatitis virus (MHV) expressing TMEV L*, we showed that L* efficiently inhibits RNase L in vivo. Interestingly, those data show that L* can functionally substitute for the MHV-encoded phosphodiesterase ns2, which acts upstream of L* in the OAS/RNase L pathway, by degrading 2-5A.",2018 Apr 13,"['Drappier, Melissa', 'Jha, Babal Kant', 'Stone, Sasha', 'Elliott, Ruth', 'Zhang, Rong', 'Vertommen, Didier', 'Weiss, Susan R.', 'Silverman, Robert H.', 'Michiels, Thomas']",PLoS Pathog,,,True
efa238c40ad849c8cc4e21024a54535556e94e22,PMC,A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A from binding to RNase L,http://dx.doi.org/10.1371/journal.ppat.1006989,PMC5927464,29652922,CC BY,"The OAS/RNase L pathway is one of the best-characterized effector pathways of the IFN antiviral response. It inhibits the replication of many viruses and ultimately promotes apoptosis of infected cells, contributing to the control of virus spread. However, viruses have evolved a range of escape strategies that act against different steps in the pathway. Here we unraveled a novel escape strategy involving Theiler’s murine encephalomyelitis virus (TMEV) L* protein. Previously we found that L* was the first viral protein binding directly RNase L. Our current data show that L* binds the ankyrin repeats R1 and R2 of RNase L and inhibits 2’-5’ oligoadenylates (2-5A) binding to RNase L. Thereby, L* prevents dimerization and oligomerization of RNase L in response to 2-5A. Using chimeric mouse hepatitis virus (MHV) expressing TMEV L*, we showed that L* efficiently inhibits RNase L in vivo. Interestingly, those data show that L* can functionally substitute for the MHV-encoded phosphodiesterase ns2, which acts upstream of L* in the OAS/RNase L pathway, by degrading 2-5A.",2018 Apr 13,"['Drappier, Melissa', 'Jha, Babal Kant', 'Stone, Sasha', 'Elliott, Ruth', 'Zhang, Rong', 'Vertommen, Didier', 'Weiss, Susan R.', 'Silverman, Robert H.', 'Michiels, Thomas']",PLoS Pathog,,,False
909fa78642adc9c7cab7de12827596e7263b67e4,PMC,A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A from binding to RNase L,http://dx.doi.org/10.1371/journal.ppat.1006989,PMC5927464,29652922,CC BY,"The OAS/RNase L pathway is one of the best-characterized effector pathways of the IFN antiviral response. It inhibits the replication of many viruses and ultimately promotes apoptosis of infected cells, contributing to the control of virus spread. However, viruses have evolved a range of escape strategies that act against different steps in the pathway. Here we unraveled a novel escape strategy involving Theiler’s murine encephalomyelitis virus (TMEV) L* protein. Previously we found that L* was the first viral protein binding directly RNase L. Our current data show that L* binds the ankyrin repeats R1 and R2 of RNase L and inhibits 2’-5’ oligoadenylates (2-5A) binding to RNase L. Thereby, L* prevents dimerization and oligomerization of RNase L in response to 2-5A. Using chimeric mouse hepatitis virus (MHV) expressing TMEV L*, we showed that L* efficiently inhibits RNase L in vivo. Interestingly, those data show that L* can functionally substitute for the MHV-encoded phosphodiesterase ns2, which acts upstream of L* in the OAS/RNase L pathway, by degrading 2-5A.",2018 Apr 13,"['Drappier, Melissa', 'Jha, Babal Kant', 'Stone, Sasha', 'Elliott, Ruth', 'Zhang, Rong', 'Vertommen, Didier', 'Weiss, Susan R.', 'Silverman, Robert H.', 'Michiels, Thomas']",PLoS Pathog,,,False
2fc90278a41ab4147345bbb85d64bc51e9a64087,PMC,A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A from binding to RNase L,http://dx.doi.org/10.1371/journal.ppat.1006989,PMC5927464,29652922,CC BY,"The OAS/RNase L pathway is one of the best-characterized effector pathways of the IFN antiviral response. It inhibits the replication of many viruses and ultimately promotes apoptosis of infected cells, contributing to the control of virus spread. However, viruses have evolved a range of escape strategies that act against different steps in the pathway. Here we unraveled a novel escape strategy involving Theiler’s murine encephalomyelitis virus (TMEV) L* protein. Previously we found that L* was the first viral protein binding directly RNase L. Our current data show that L* binds the ankyrin repeats R1 and R2 of RNase L and inhibits 2’-5’ oligoadenylates (2-5A) binding to RNase L. Thereby, L* prevents dimerization and oligomerization of RNase L in response to 2-5A. Using chimeric mouse hepatitis virus (MHV) expressing TMEV L*, we showed that L* efficiently inhibits RNase L in vivo. Interestingly, those data show that L* can functionally substitute for the MHV-encoded phosphodiesterase ns2, which acts upstream of L* in the OAS/RNase L pathway, by degrading 2-5A.",2018 Apr 13,"['Drappier, Melissa', 'Jha, Babal Kant', 'Stone, Sasha', 'Elliott, Ruth', 'Zhang, Rong', 'Vertommen, Didier', 'Weiss, Susan R.', 'Silverman, Robert H.', 'Michiels, Thomas']",PLoS Pathog,,,False
07928c96123e42473f3b02e7cfa13ba8b53d591e,PMC,A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A from binding to RNase L,http://dx.doi.org/10.1371/journal.ppat.1006989,PMC5927464,29652922,CC BY,"The OAS/RNase L pathway is one of the best-characterized effector pathways of the IFN antiviral response. It inhibits the replication of many viruses and ultimately promotes apoptosis of infected cells, contributing to the control of virus spread. However, viruses have evolved a range of escape strategies that act against different steps in the pathway. Here we unraveled a novel escape strategy involving Theiler’s murine encephalomyelitis virus (TMEV) L* protein. Previously we found that L* was the first viral protein binding directly RNase L. Our current data show that L* binds the ankyrin repeats R1 and R2 of RNase L and inhibits 2’-5’ oligoadenylates (2-5A) binding to RNase L. Thereby, L* prevents dimerization and oligomerization of RNase L in response to 2-5A. Using chimeric mouse hepatitis virus (MHV) expressing TMEV L*, we showed that L* efficiently inhibits RNase L in vivo. Interestingly, those data show that L* can functionally substitute for the MHV-encoded phosphodiesterase ns2, which acts upstream of L* in the OAS/RNase L pathway, by degrading 2-5A.",2018 Apr 13,"['Drappier, Melissa', 'Jha, Babal Kant', 'Stone, Sasha', 'Elliott, Ruth', 'Zhang, Rong', 'Vertommen, Didier', 'Weiss, Susan R.', 'Silverman, Robert H.', 'Michiels, Thomas']",PLoS Pathog,,,False
29d51bb07c2434b1a2f2adf2a0ea52d82c8dfd24,PMC,Nucleolar-nucleoplasmic shuttling of TARG1 and its control by DNA damage-induced poly-ADP-ribosylation and by nucleolar transcription,http://dx.doi.org/10.1038/s41598-018-25137-w,PMC5928194,29712969,CC BY,"Macrodomains are conserved protein folds associated with ADP-ribose binding and turnover. ADP-ribosylation is a posttranslational modification catalyzed primarily by ARTD (aka PARP) enzymes in cells. ARTDs transfer either single or multiple ADP-ribose units to substrates, resulting in mono- or poly-ADP-ribosylation. TARG1/C6orf130 is a macrodomain protein that hydrolyzes mono-ADP-ribosylation and interacts with poly-ADP-ribose chains. Interactome analyses revealed that TARG1 binds strongly to ribosomes and proteins associated with rRNA processing and ribosomal assembly factors. TARG1 localized to transcriptionally active nucleoli, which occurred independently of ADP-ribose binding. TARG1 shuttled continuously between nucleoli and nucleoplasm. In response to DNA damage, which activates ARTD1/2 (PARP1/2) and promotes synthesis of poly-ADP-ribose chains, TARG1 re-localized to the nucleoplasm. This was dependent on the ability of TARG1 to bind to poly-ADP-ribose. These findings are consistent with the observed ability of TARG1 to competitively interact with RNA and PAR chains. We propose a nucleolar role of TARG1 in ribosome assembly or quality control that is stalled when TARG1 is re-located to sites of DNA damage.",2018 Apr 30,"['Bütepage, Mareike', 'Preisinger, Christian', 'von Kriegsheim, Alexander', 'Scheufen, Anja', 'Lausberg, Eva', 'Li, Jinyu', 'Kappes, Ferdinand', 'Feederle, Regina', 'Ernst, Sabrina', 'Eckei, Laura', 'Krieg, Sarah', 'Müller-Newen, Gerhard', 'Rossetti, Giulia', 'Feijs, Karla L. H.', 'Verheugd, Patricia', 'Lüscher, Bernhard']",Sci Rep,,,True
5993ed074d10970cc93e82fc038ae239f61a16e8,PMC,Nucleolar-nucleoplasmic shuttling of TARG1 and its control by DNA damage-induced poly-ADP-ribosylation and by nucleolar transcription,http://dx.doi.org/10.1038/s41598-018-25137-w,PMC5928194,29712969,CC BY,"Macrodomains are conserved protein folds associated with ADP-ribose binding and turnover. ADP-ribosylation is a posttranslational modification catalyzed primarily by ARTD (aka PARP) enzymes in cells. ARTDs transfer either single or multiple ADP-ribose units to substrates, resulting in mono- or poly-ADP-ribosylation. TARG1/C6orf130 is a macrodomain protein that hydrolyzes mono-ADP-ribosylation and interacts with poly-ADP-ribose chains. Interactome analyses revealed that TARG1 binds strongly to ribosomes and proteins associated with rRNA processing and ribosomal assembly factors. TARG1 localized to transcriptionally active nucleoli, which occurred independently of ADP-ribose binding. TARG1 shuttled continuously between nucleoli and nucleoplasm. In response to DNA damage, which activates ARTD1/2 (PARP1/2) and promotes synthesis of poly-ADP-ribose chains, TARG1 re-localized to the nucleoplasm. This was dependent on the ability of TARG1 to bind to poly-ADP-ribose. These findings are consistent with the observed ability of TARG1 to competitively interact with RNA and PAR chains. We propose a nucleolar role of TARG1 in ribosome assembly or quality control that is stalled when TARG1 is re-located to sites of DNA damage.",2018 Apr 30,"['Bütepage, Mareike', 'Preisinger, Christian', 'von Kriegsheim, Alexander', 'Scheufen, Anja', 'Lausberg, Eva', 'Li, Jinyu', 'Kappes, Ferdinand', 'Feederle, Regina', 'Ernst, Sabrina', 'Eckei, Laura', 'Krieg, Sarah', 'Müller-Newen, Gerhard', 'Rossetti, Giulia', 'Feijs, Karla L. H.', 'Verheugd, Patricia', 'Lüscher, Bernhard']",Sci Rep,,,True
0266337807a2aab25e7dc43967cba01860fe5d86,PMC,"A Combined Syndromic Approach to Examine Viral, Bacterial, and Parasitic Agents among Febrile Patients: A Pilot Study in Kilombero, Tanzania",http://dx.doi.org/10.4269/ajtmh.17-0421,PMC5929188,29280432,CC BY,"The use of fever syndromic surveillance in sub-Saharan Africa is an effective approach to determine the prevalence of both malarial and nonmalarial infectious agents. We collected both blood and naso/oro-pharyngeal (NP/OP) swabs from consecutive consenting patients ≥ 1 year of age, with an axillary temperature ≥ 37.5°C, and symptom onset of ≤ 5 days. Specimens were analyzed using both acute febrile illness (AFI) and respiratory TaqMan array cards (Resp TAC) for multiagent detection of 56 different bloodstream and respiratory agents. In addition, we collected epidemiologic data to further characterize our patient population. We enrolled 205 febrile patients, including 70 children (1 < 15 years of age; 34%) and 135 adults (≥ 15 years of age; 66%). AFI TAC and Resp TAC were performed on 191 whole blood specimens and 115 NP/OP specimens, respectively. We detected nucleic acid for Plasmodium (57%), Leptospira (2%), and dengue virus (1%) among blood specimens. In addition, we detected 17 different respiratory agents, most notably, Haemophilus influenzae (64%), Streptococcus pneumonia (56%), Moraxella catarrhalis (39%), and respiratory syncytial virus (11%) among NP/OP specimens. Overall median cycle threshold was measured at 26.5. This study provides a proof-of-concept for the use of a multiagent diagnostic approach for exploratory research on febrile illness and underscores the utility of quantitative molecular diagnostics in complex epidemiologic settings of sub-Saharan Africa.",2018 Feb 26,"['Hercik, Christine', 'Cosmas, Leonard', 'Mogeni, Ondari D.', 'Wamola, Newton', 'Kohi, Wanze', 'Houpt, Eric', 'Liu, Jie', 'Ochieng, Caroline', 'Onyango, Clayton', 'Fields, Barry', 'Mfinanga, Sayoki', 'Montgomery, Joel M.']",Am J Trop Med Hyg,,,True
3f9135d566bb577a6023553e6245603b229e934e,PMC,"A Combined Syndromic Approach to Examine Viral, Bacterial, and Parasitic Agents among Febrile Patients: A Pilot Study in Kilombero, Tanzania",http://dx.doi.org/10.4269/ajtmh.17-0421,PMC5929188,29280432,CC BY,"The use of fever syndromic surveillance in sub-Saharan Africa is an effective approach to determine the prevalence of both malarial and nonmalarial infectious agents. We collected both blood and naso/oro-pharyngeal (NP/OP) swabs from consecutive consenting patients ≥ 1 year of age, with an axillary temperature ≥ 37.5°C, and symptom onset of ≤ 5 days. Specimens were analyzed using both acute febrile illness (AFI) and respiratory TaqMan array cards (Resp TAC) for multiagent detection of 56 different bloodstream and respiratory agents. In addition, we collected epidemiologic data to further characterize our patient population. We enrolled 205 febrile patients, including 70 children (1 < 15 years of age; 34%) and 135 adults (≥ 15 years of age; 66%). AFI TAC and Resp TAC were performed on 191 whole blood specimens and 115 NP/OP specimens, respectively. We detected nucleic acid for Plasmodium (57%), Leptospira (2%), and dengue virus (1%) among blood specimens. In addition, we detected 17 different respiratory agents, most notably, Haemophilus influenzae (64%), Streptococcus pneumonia (56%), Moraxella catarrhalis (39%), and respiratory syncytial virus (11%) among NP/OP specimens. Overall median cycle threshold was measured at 26.5. This study provides a proof-of-concept for the use of a multiagent diagnostic approach for exploratory research on febrile illness and underscores the utility of quantitative molecular diagnostics in complex epidemiologic settings of sub-Saharan Africa.",2018 Feb 26,"['Hercik, Christine', 'Cosmas, Leonard', 'Mogeni, Ondari D.', 'Wamola, Newton', 'Kohi, Wanze', 'Houpt, Eric', 'Liu, Jie', 'Ochieng, Caroline', 'Onyango, Clayton', 'Fields, Barry', 'Mfinanga, Sayoki', 'Montgomery, Joel M.']",Am J Trop Med Hyg,,,False
afa40d52e8f5ebf6996e417c9cfeff109b7bb619,PMC,Generalists and Specialists: A New View of How MHC Class I Molecules Fight Infectious Pathogens,http://dx.doi.org/10.1016/j.it.2018.01.001,PMC5929564,29396014,CC BY,"In comparison with the major histocompatibility complexes (MHCs) of typical mammals, the chicken MHC is simple and compact with a single dominantly expressed class I molecule that can determine the immune response. In addition to providing useful information for the poultry industry and allowing insights into the evolution of the adaptive immune system, the simplicity of the chicken MHC has allowed the discovery of phenomena that are more difficult to discern in the more complicated mammalian systems. This review discusses the new concept that poorly expressed promiscuous class I alleles act as generalists to protect against a wide variety of infectious pathogens, while highly expressed fastidious class I alleles can act as specialists to protect against new and dangerous pathogens.",2018 May,"Kaufman, Jim",Trends Immunol,,,False
c7e5e64683c8dbf4d6585fd231d20a4d8ee3885e,PMC,Selective Packaging in Murine Coronavirus Promotes Virulence by Limiting Type I Interferon Responses,http://dx.doi.org/10.1128/mBio.00272-18,PMC5930304,29717007,CC BY,"Selective packaging is a mechanism used by multiple virus families to specifically incorporate genomic RNA (gRNA) into virions and exclude other types of RNA. Lineage A betacoronaviruses incorporate a 95-bp stem-loop structure, the packaging signal (PS), into the nsp15 locus of ORF1b that is both necessary and sufficient for the packaging of RNAs. However, unlike other viral PSs, where mutations generally resulted in viral replication defects, mutation of the coronavirus (CoV) PS results in large increases in subgenomic RNA packaging with minimal effects on gRNA packaging in vitro and on viral titers. Here, we show that selective packaging is also required for viral evasion of the innate immune response and optimal pathogenicity. We engineered two distinct PS mutants in two different strains of murine hepatitis virus (MHV) that packaged increased levels of subgenomic RNAs, negative-sense genomic RNA, and even cellular RNAs. All PS mutant viruses replicated normally in vitro but caused dramatically reduced lethality and weight loss in vivo. PS mutant virus infection of bone marrow-derived macrophages resulted in increased interferon (IFN) production, indicating that the innate immune system limited the replication and/or pathogenesis of PS mutant viruses in vivo. PS mutant viruses remained attenuated in MAVS(−/−) and Toll-like receptor 7-knockout (TLR7(−/−)) mice, two well-known RNA sensors for CoVs, but virulence was restored in interferon alpha/beta receptor-knockout (IFNAR(−/−)) mice or in MAVS(−/−) mice treated with IFNAR-blocking antibodies. Together, these data indicate that coronaviruses promote virulence by utilizing selective packaging to avoid innate immune detection.",2018 May 1,"['Athmer, Jeremiah', 'Fehr, Anthony R.', 'Grunewald, Matthew E.', 'Qu, Wen', 'Wheeler, D. Lori', 'Graepel, Kevin W.', 'Channappanavar, Rudragouda', 'Sekine, Aimee', 'Aldabeeb, Dana Saud', 'Gale, Michael', 'Denison, Mark R.', 'Perlman, Stanley']",mBio,,,True
d78ca1eea9e94aa3dce73f05553d3ceb91f4c886,PMC,"A triplex quantitative real-time PCR assay for differential detection of human adenovirus serotypes 2, 3 and 7",http://dx.doi.org/10.1186/s12985-018-0983-x,PMC5930744,29716642,CC BY,"BACKGROUND: Human adenovirus (HAdV) serotypes 2, 3 and 7 are more prevalent than other serotypes and have been associated with severe pneumonia in pediatric children. Molecular typing of HAdV is not routinely performed in clinical diagnostic laboratories as it is time-consuming and labor-intensive. METHODS: In the present study, we developed a triplex quantitative real-time PCR assay (tq-PCR) in a single closed tube for differential detection and quantitative analysis of HAdV serotypes 2, 3 and 7. The sensitivity, specificity, reproducibility and clinical performance of tq-PCR were evaluated. RESULTS: The analytical sensitivity of the tq-PCR was 100 copies/reaction for each of HAdV serotypes 2, 3 and 7, and no cross-reaction with other common respiratory viruses or HAdV serotypes 1,4,5,6,31,55 and 57 was observed. The coefficients of variation (CV) of intra-assay and inter-assay were between 0.6% to 3.6%. Of 138 previously-defined HAdV-positive nasopharyngeal aspirates samples tested, the detection agreement between tq-PCR and nested PCR was 96.38% (133/138). CONCLUSION: The proposed tq-PCR assay is a sensitive, specific and reproducible method and has the potential for clinical use in the rapid and differential detection and quantitation of HAdV serotypes 2, 3 and 7.",2018 May 2,"['Qiu, Fang-zhou', 'Shen, Xin-xin', 'Zhao, Meng-chuan', 'Zhao, Li', 'Duan, Su-xia', 'Chen, Chen', 'Qi, Ju-Ju', 'Li, Gui-xia', 'Wang, Le', 'Feng, Zhi-shan', 'Ma, Xue-jun']",Virol J,,,True
e29425dbc37811e314513aed5880fbd088f52971,PMC,MERS transmission and risk factors: a systematic review,http://dx.doi.org/10.1186/s12889-018-5484-8,PMC5930778,29716568,CC BY,"BACKGROUND: Since Middle East respiratory syndrome (MERS) infection was first reported in 2012, many studies have analysed its transmissibility and severity. However, the methodology and results of these studies have varied, and there has been no systematic review of MERS. This study reviews the characteristics and associated risk factors of MERS. METHOD: We searched international (PubMed, ScienceDirect, Cochrane) and Korean databases (DBpia, KISS) for English- or Korean-language articles using the terms “MERS” and “Middle East respiratory syndrome”. Only human studies with > 20 participants were analysed to exclude studies with low representation. Epidemiologic studies with information on transmissibility and severity of MERS as well as studies containing MERS risk factors were included. RESULT: A total of 59 studies were included. Most studies from Saudi Arabia reported higher mortality (22–69.2%) than those from South Korea (20.4%). While the R(0) value in Saudi Arabia was < 1 in all but one study, in South Korea, the R(0) value was 2.5–8.09 in the early stage and decreased to < 1 in the later stage. The incubation period was 4.5–5.2 days in Saudi Arabia and 6–7.8 days in South Korea. Duration from onset was 4–10 days to confirmation, 2.9–5.3 days to hospitalization, 11–17 days to death, and 14–20 days to discharge. Older age and concomitant disease were the most common factors related to MERS infection, severity, and mortality. CONCLUSION: The transmissibility and severity of MERS differed by outbreak region and patient characteristics. Further studies assessing the risk of MERS should consider these factors.",2018 May 2,"['Park, Ji-Eun', 'Jung, Soyoung', 'Kim, Aeran', 'Park, Ji-Eun']",BMC Public Health,,,True
bf776a96c393673a249783721adaaecbd2c82a8b,PMC,Clinical and Molecular Epidemiology of Human Parainfluenza Viruses 1–4 in Children from Viet Nam,http://dx.doi.org/10.1038/s41598-018-24767-4,PMC5931535,29717150,CC BY,"HPIVs are serologically and genetically grouped into four species that account for up to 10% of all hospitalizations due to acute respiratory infection in children under the age of five. Genetic and epidemiological data for the four HPIVs derived from two pediatric cohorts in Viet Nam are presented. Respiratory samples were screened for HPIV1–4 by real-time PCR. Demographic and clinical data of patients infected with different HPIV were compared. We used a hemi-nested PCR approach to generate viral genome sequences from HPIV-positive samples and conducted a comprehensive phylogenetic analysis. In total, 170 samples tested positive for HPIV. HPIV3 was most commonly detected in our cohort and 80 co-detections of HPIV with other respiratory viruses were found. Phylogenetic analyses suggest local endemic circulation as well as punctuated introductions of new HPIV lineages. Viral gene flow analysis revealed that Viet Nam is a net importer of viral genetic diversity. Epidemiological analyses imply similar disease severity for all HPIV species. HPIV sequences from Viet Nam formed local clusters and were interspersed with sequences from diverse geographic regions. Combined, this new knowledge will help to investigate global HPIV circulation patterns in more detail and ultimately define more suitable vaccine strains.",2018 May 1,"['Linster, Martin', 'Do, Lien Anh Ha', 'Minh, Ngo Ngoc Quang', 'Chen, Yihui', 'Zhe, Zhu', 'Tuan, Tran Anh', 'Tuan, Ha Manh', 'Su, Yvonne C. F.', 'van Doorn, H. Rogier', 'Moorthy, Mahesh', 'Smith, Gavin J. D.']",Sci Rep,,,False
8161866d70fb76ec6e2c5d78f06c2884b92fb39e,PMC,Clinical and Molecular Epidemiology of Human Parainfluenza Viruses 1–4 in Children from Viet Nam,http://dx.doi.org/10.1038/s41598-018-24767-4,PMC5931535,29717150,CC BY,"HPIVs are serologically and genetically grouped into four species that account for up to 10% of all hospitalizations due to acute respiratory infection in children under the age of five. Genetic and epidemiological data for the four HPIVs derived from two pediatric cohorts in Viet Nam are presented. Respiratory samples were screened for HPIV1–4 by real-time PCR. Demographic and clinical data of patients infected with different HPIV were compared. We used a hemi-nested PCR approach to generate viral genome sequences from HPIV-positive samples and conducted a comprehensive phylogenetic analysis. In total, 170 samples tested positive for HPIV. HPIV3 was most commonly detected in our cohort and 80 co-detections of HPIV with other respiratory viruses were found. Phylogenetic analyses suggest local endemic circulation as well as punctuated introductions of new HPIV lineages. Viral gene flow analysis revealed that Viet Nam is a net importer of viral genetic diversity. Epidemiological analyses imply similar disease severity for all HPIV species. HPIV sequences from Viet Nam formed local clusters and were interspersed with sequences from diverse geographic regions. Combined, this new knowledge will help to investigate global HPIV circulation patterns in more detail and ultimately define more suitable vaccine strains.",2018 May 1,"['Linster, Martin', 'Do, Lien Anh Ha', 'Minh, Ngo Ngoc Quang', 'Chen, Yihui', 'Zhe, Zhu', 'Tuan, Tran Anh', 'Tuan, Ha Manh', 'Su, Yvonne C. F.', 'van Doorn, H. Rogier', 'Moorthy, Mahesh', 'Smith, Gavin J. D.']",Sci Rep,,,True
edf80ff17939beaa54813b0452ae10e7733007df,PMC,Exploring Leptospiral proteomes to identify potential candidates for vaccine design against Leptospirosis using an immunoinformatics approach,http://dx.doi.org/10.1038/s41598-018-25281-3,PMC5932004,29720698,CC BY,"Leptospirosis is the most widespread zoonotic disease, estimated to cause severe infection in more than one million people each year, particularly in developing countries of tropical areas. Several factors such as variable and nonspecific clinical manifestation, existence of large number of serovars and asymptomatic hosts spreading infection, poor sanitation and lack of an effective vaccine make prophylaxis difficult. Consequently, there is an urgent need to develop an effective vaccine to halt its spread all over the world. In this study, an immunoinformatics approach was employed to identify the most vital and effective immunogenic protein from the proteome of Leptospira interrogans serovar Copenhageni strain L1-130 that may be suitable to stimulate a significant immune response aiding in the development of peptide vaccine against leptospirosis. Both B-cell and T-cell (Helper T-lymphocyte (HTL) and cytotoxic T lymphocyte (CTL)) epitopes were predicted for the conserved and most immunogenic outer membrane lipoprotein. Further, the binding interaction of CTL epitopes with Major Histocompatibility Complex class I (MHC-I) was evaluated using docking techniques. A Molecular Dynamics Simulation study was also performed to evaluate the stability of the resulting epitope-MHC-I complexes. Overall, this study provides novel vaccine candidates and may prompt further development of vaccines against leptospirosis.",2018 May 2,"['Lata, Kumari Snehkant', 'Kumar, Swapnil', 'Vaghasia, Vibhisha', 'Sharma, Priyanka', 'Bhairappanvar, Shivarudrappa B.', 'Soni, Subhash', 'Das, Jayashankar']",Sci Rep,,,False
89a3e7a6691f7cc1f79dc465fca8968f1a1739f8,PMC,Exploring Leptospiral proteomes to identify potential candidates for vaccine design against Leptospirosis using an immunoinformatics approach,http://dx.doi.org/10.1038/s41598-018-25281-3,PMC5932004,29720698,CC BY,"Leptospirosis is the most widespread zoonotic disease, estimated to cause severe infection in more than one million people each year, particularly in developing countries of tropical areas. Several factors such as variable and nonspecific clinical manifestation, existence of large number of serovars and asymptomatic hosts spreading infection, poor sanitation and lack of an effective vaccine make prophylaxis difficult. Consequently, there is an urgent need to develop an effective vaccine to halt its spread all over the world. In this study, an immunoinformatics approach was employed to identify the most vital and effective immunogenic protein from the proteome of Leptospira interrogans serovar Copenhageni strain L1-130 that may be suitable to stimulate a significant immune response aiding in the development of peptide vaccine against leptospirosis. Both B-cell and T-cell (Helper T-lymphocyte (HTL) and cytotoxic T lymphocyte (CTL)) epitopes were predicted for the conserved and most immunogenic outer membrane lipoprotein. Further, the binding interaction of CTL epitopes with Major Histocompatibility Complex class I (MHC-I) was evaluated using docking techniques. A Molecular Dynamics Simulation study was also performed to evaluate the stability of the resulting epitope-MHC-I complexes. Overall, this study provides novel vaccine candidates and may prompt further development of vaccines against leptospirosis.",2018 May 2,"['Lata, Kumari Snehkant', 'Kumar, Swapnil', 'Vaghasia, Vibhisha', 'Sharma, Priyanka', 'Bhairappanvar, Shivarudrappa B.', 'Soni, Subhash', 'Das, Jayashankar']",Sci Rep,,,True
da3dea36182741e1b3699e372f16e1f0bb2fd315,PMC,CE-BLAST makes it possible to compute antigenic similarity for newly emerging pathogens,http://dx.doi.org/10.1038/s41467-018-04171-2,PMC5932059,29720583,CC BY,"Major challenges in vaccine development include rapidly selecting or designing immunogens for raising cross-protective immunity against different intra- or inter-subtypic pathogens, especially for the newly emerging varieties. Here we propose a computational method, Conformational Epitope (CE)-BLAST, for calculating the antigenic similarity among different pathogens with stable and high performance, which is independent of the prior binding-assay information, unlike the currently available models that heavily rely on the historical experimental data. Tool validation incorporates influenza-related experimental data sufficient for stability and reliability determination. Application to dengue-related data demonstrates high harmonization between the computed clusters and the experimental serological data, undetectable by classical grouping. CE-BLAST identifies the potential cross-reactive epitope between the recent zika pathogen and the dengue virus, precisely corroborated by experimental data. The high performance of the pathogens without the experimental binding data suggests the potential utility of CE-BLAST to rapidly design cross-protective vaccines or promptly determine the efficacy of the currently marketed vaccine against emerging pathogens, which are the critical factors for containing emerging disease outbreaks.",2018 May 2,"['Qiu, Tianyi', 'Yang, Yiyan', 'Qiu, Jingxuan', 'Huang, Yang', 'Xu, Tianlei', 'Xiao, Han', 'Wu, Dingfeng', 'Zhang, Qingchen', 'Zhou, Chen', 'Zhang, Xiaoyan', 'Tang, Kailin', 'Xu, Jianqing', 'Cao, Zhiwei']",Nat Commun,,,True
99b91c8b0a5455bca54167c5abb7c0dfdbf032c6,PMC,CE-BLAST makes it possible to compute antigenic similarity for newly emerging pathogens,http://dx.doi.org/10.1038/s41467-018-04171-2,PMC5932059,29720583,CC BY,"Major challenges in vaccine development include rapidly selecting or designing immunogens for raising cross-protective immunity against different intra- or inter-subtypic pathogens, especially for the newly emerging varieties. Here we propose a computational method, Conformational Epitope (CE)-BLAST, for calculating the antigenic similarity among different pathogens with stable and high performance, which is independent of the prior binding-assay information, unlike the currently available models that heavily rely on the historical experimental data. Tool validation incorporates influenza-related experimental data sufficient for stability and reliability determination. Application to dengue-related data demonstrates high harmonization between the computed clusters and the experimental serological data, undetectable by classical grouping. CE-BLAST identifies the potential cross-reactive epitope between the recent zika pathogen and the dengue virus, precisely corroborated by experimental data. The high performance of the pathogens without the experimental binding data suggests the potential utility of CE-BLAST to rapidly design cross-protective vaccines or promptly determine the efficacy of the currently marketed vaccine against emerging pathogens, which are the critical factors for containing emerging disease outbreaks.",2018 May 2,"['Qiu, Tianyi', 'Yang, Yiyan', 'Qiu, Jingxuan', 'Huang, Yang', 'Xu, Tianlei', 'Xiao, Han', 'Wu, Dingfeng', 'Zhang, Qingchen', 'Zhou, Chen', 'Zhang, Xiaoyan', 'Tang, Kailin', 'Xu, Jianqing', 'Cao, Zhiwei']",Nat Commun,,,True
94d37f29233a978eb72f3803abe072e9b19419a7,PMC,CE-BLAST makes it possible to compute antigenic similarity for newly emerging pathogens,http://dx.doi.org/10.1038/s41467-018-04171-2,PMC5932059,29720583,CC BY,"Major challenges in vaccine development include rapidly selecting or designing immunogens for raising cross-protective immunity against different intra- or inter-subtypic pathogens, especially for the newly emerging varieties. Here we propose a computational method, Conformational Epitope (CE)-BLAST, for calculating the antigenic similarity among different pathogens with stable and high performance, which is independent of the prior binding-assay information, unlike the currently available models that heavily rely on the historical experimental data. Tool validation incorporates influenza-related experimental data sufficient for stability and reliability determination. Application to dengue-related data demonstrates high harmonization between the computed clusters and the experimental serological data, undetectable by classical grouping. CE-BLAST identifies the potential cross-reactive epitope between the recent zika pathogen and the dengue virus, precisely corroborated by experimental data. The high performance of the pathogens without the experimental binding data suggests the potential utility of CE-BLAST to rapidly design cross-protective vaccines or promptly determine the efficacy of the currently marketed vaccine against emerging pathogens, which are the critical factors for containing emerging disease outbreaks.",2018 May 2,"['Qiu, Tianyi', 'Yang, Yiyan', 'Qiu, Jingxuan', 'Huang, Yang', 'Xu, Tianlei', 'Xiao, Han', 'Wu, Dingfeng', 'Zhang, Qingchen', 'Zhou, Chen', 'Zhang, Xiaoyan', 'Tang, Kailin', 'Xu, Jianqing', 'Cao, Zhiwei']",Nat Commun,,,False
0eda9491295d6a851db35c358ac0c4fe956dce1c,PMC,CE-BLAST makes it possible to compute antigenic similarity for newly emerging pathogens,http://dx.doi.org/10.1038/s41467-018-04171-2,PMC5932059,29720583,CC BY,"Major challenges in vaccine development include rapidly selecting or designing immunogens for raising cross-protective immunity against different intra- or inter-subtypic pathogens, especially for the newly emerging varieties. Here we propose a computational method, Conformational Epitope (CE)-BLAST, for calculating the antigenic similarity among different pathogens with stable and high performance, which is independent of the prior binding-assay information, unlike the currently available models that heavily rely on the historical experimental data. Tool validation incorporates influenza-related experimental data sufficient for stability and reliability determination. Application to dengue-related data demonstrates high harmonization between the computed clusters and the experimental serological data, undetectable by classical grouping. CE-BLAST identifies the potential cross-reactive epitope between the recent zika pathogen and the dengue virus, precisely corroborated by experimental data. The high performance of the pathogens without the experimental binding data suggests the potential utility of CE-BLAST to rapidly design cross-protective vaccines or promptly determine the efficacy of the currently marketed vaccine against emerging pathogens, which are the critical factors for containing emerging disease outbreaks.",2018 May 2,"['Qiu, Tianyi', 'Yang, Yiyan', 'Qiu, Jingxuan', 'Huang, Yang', 'Xu, Tianlei', 'Xiao, Han', 'Wu, Dingfeng', 'Zhang, Qingchen', 'Zhou, Chen', 'Zhang, Xiaoyan', 'Tang, Kailin', 'Xu, Jianqing', 'Cao, Zhiwei']",Nat Commun,,,True
20320bc56f02e0fc4bc6430ddb0efa564db40cd1,PMC,Ebolaviruses: New roles for old proteins,http://dx.doi.org/10.1371/journal.pntd.0006349,PMC5933699,29723187,CC BY,"In 2014, the world witnessed the largest Ebolavirus outbreak in recorded history. The subsequent humanitarian effort spurred extensive research, significantly enhancing our understanding of ebolavirus replication and pathogenicity. The main functions of each ebolavirus protein have been studied extensively since the discovery of the virus in 1976; however, the recent expansion of ebolavirus research has led to the discovery of new protein functions. These newly discovered roles are revealing new mechanisms of virus replication and pathogenicity, whilst enhancing our understanding of the broad functions of each ebolavirus viral protein (VP). Many of these new functions appear to be unrelated to the protein’s primary function during virus replication. Such new functions range from bystander T-lymphocyte death caused by VP40-secreted exosomes to new roles for VP24 in viral particle formation. This review highlights the newly discovered roles of ebolavirus proteins in order to provide a more encompassing view of ebolavirus replication and pathogenicity.",2018 May 3,"['Cantoni, Diego', 'Rossman, Jeremy S.']",PLoS Negl Trop Dis,,,True
8e3f91d0836afefc7a5e71a8e7db1155af4c2c8c,PMC,Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins,http://dx.doi.org/10.1371/journal.ppat.1007009,PMC5933801,29684066,CC BY,"As cell-invading molecular machinery, coronavirus spike proteins pose an evolutionary conundrum due to their high divergence. In this study, we determined the cryo-EM structure of avian infectious bronchitis coronavirus (IBV) spike protein from the γ-genus. The trimeric IBV spike ectodomain contains three receptor-binding S1 heads and a trimeric membrane-fusion S2 stalk. While IBV S2 is structurally similar to those from the other genera, IBV S1 possesses structural features that are unique to different other genera, thereby bridging these diverse spikes into an evolutionary spectrum. Specifically, among different genera, the two domains of S1, the N-terminal domain (S1-NTD) and C-terminal domain (S1-CTD), diverge from simpler tertiary structures and quaternary packing to more complex ones, leading to different functions of the spikes in receptor usage and membrane fusion. Based on the above structural and functional comparisons, we propose that the evolutionary spectrum of coronavirus spikes follows the order of α-, δ-, γ-, and β-genus. This study has provided insight into the evolutionary relationships among coronavirus spikes and deepened our understanding of their structural and functional diversity.",2018 Apr 23,"['Shang, Jian', 'Zheng, Yuan', 'Yang, Yang', 'Liu, Chang', 'Geng, Qibin', 'Luo, Chuming', 'Zhang, Wei', 'Li, Fang']",PLoS Pathog,,,True
da31b90321637cd3a3464969817540a35d6a597c,PMC,Controlled fluorescence quenching by antibody-conjugated graphene oxide to measure tau protein,http://dx.doi.org/10.1098/rsos.171808,PMC5936912,29765647,CC BY,"We report an ultrasensitive immunoassay for tau protein—a key marker of Alzheimer's disease. This sensing platform relies on graphene oxide (GO) surfaces conjugated with anti-human tau antibody to provide quantitative binding sites for the tau protein. The GO quenches standard fluorescein isothiocyanate labelled tau (tau-FITC) when tau protein and tau-FITC are both present and compete for the binding sites. This change in fluorescence signal can be used to quantitate tau protein. In contrast with traditional enzyme-linked immunosorbent assay (ELISA), our method does not require enzyme-linked secondary antibodies for protein recognition nor does it require an enzyme substrate for optical signal generation. This requires fewer reagents and has less systematic error than the antigen–antibody recognition steps in ELISA. Our method has a tau protein detection limit of 0.14 pmol ml(−1) in buffer. This approach could be developed into a promising biosensor for the detection of tau protein and may be useful in the clinical diagnosis of tau-induced neurodegeneration syndromes.",2018 Apr 11,"['Huang, Ao', 'Zhang, Luning', 'Li, Weiwei', 'Ma, Zeyu', 'Shuo, Shi', 'Yao, Tianming']",R Soc Open Sci,,,True
b4a0898920270c599908b3efbf4f7342a8b56c8e,PMC,Nod2 is required for antigen-specific humoral responses against antigens orally delivered using a recombinant Lactobacillus vaccine platform,http://dx.doi.org/10.1371/journal.pone.0196950,PMC5937747,29734365,CC BY,"Safe and efficacious orally-delivered mucosal vaccine platforms are desperately needed to combat the plethora of mucosally transmitted pathogens. Lactobacillus spp. have emerged as attractive candidates to meet this need and are known to activate the host innate immune response in a species- and strain-specific manner. For selected bacterial isolates and mutants, we investigated the role of key innate immune pathways required for induction of innate and subsequent adaptive immune responses. Co-culture of murine macrophages with L. gasseri (strain NCK1785), L. acidophilus (strain NCFM), or NCFM-derived mutants—NCK2025 and NCK2031—elicited an M2b-like phenotype associated with TH2 skewing and immune regulatory function. For NCFM, this M2b phenotype was dependent on expression of lipoteichoic acid and S layer proteins. Through the use of macrophage genetic knockouts, we identified Toll-like receptor 2 (TLR2), the cytosolic nucleotide-binding oligomerization domain containing 2 (NOD2) receptor, and the inflammasome-associated caspase-1 as contributors to macrophage activation, with NOD2 cooperating with caspase-1 to induce inflammasome derived interleukin (IL)-1β in a pyroptosis-independent fashion. Finally, utilizing an NCFM-based mucosal vaccine platform with surface expression of human immunodeficiency virus type 1 (HIV-1) Gag or membrane proximal external region (MPER), we demonstrated that NOD2 signaling is required for antigen-specific mucosal and systemic humoral responses. We show that lactobacilli differentially utilize innate immune pathways and highlight NOD2 as a key mediator of macrophage function and antigen-specific humoral responses to a Lactobacillus acidophilus mucosal vaccine platform.",2018 May 7,"['Bumgardner, Sara A.', 'Zhang, Lin', 'LaVoy, Alora S.', 'Andre, Barbara', 'Frank, Chad B.', 'Kajikawa, Akinobu', 'Klaenhammer, Todd R.', 'Dean, Gregg A.']",PLoS One,,,True
f9162c1be900c7bab2cc52de3e8cdef666c4824c,PMC,Microbiota epitope similarity either dampens or enhances the immunogenicity of disease-associated antigenic epitopes,http://dx.doi.org/10.1371/journal.pone.0196551,PMC5937769,29734356,CC BY,"The microbiome influences adaptive immunity and molecular mimicry influences T cell reactivity. Here, we evaluated whether the sequence similarity of various antigens to the microbiota dampens or increases immunogenicity of T cell epitopes. Sets of epitopes and control sequences derived from 38 antigenic categories (infectious pathogens, allergens, autoantigens) were retrieved from the Immune Epitope Database (IEDB). Their similarity to microbiome sequences was calculated using the BLOSUM62 matrix. We found that sequence similarity was associated with either dampened (tolerogenic; e.g. most allergens) or increased (inflammatory; e.g. Dengue and West Nile viruses) likelihood of a peptide being immunogenic as a function of epitope source category. Ten-fold cross-validation and validation using sets of manually curated epitopes and non-epitopes derived from allergens were used to confirm these initial observations. Furthermore, the genus from which the microbiome homologous sequences were derived influenced whether a tolerogenic versus inflammatory modulatory effect was observed, with Fusobacterium most associated with inflammatory influences and Bacteroides most associated with tolerogenic influences. We validated these effects using PBMCs stimulated with various sets of microbiome peptides. “Tolerogenic” microbiome peptides elicited IL-10 production, “inflammatory” peptides elicited mixed IL-10/IFNγ production, while microbiome epitopes homologous to self were completely unreactive for both cytokines. We also tested the sequence similarity of cockroach epitopes to specific microbiome sequences derived from households of cockroach allergic individuals and non-allergic controls. Microbiomes from cockroach allergic households were less likely to contain sequences homologous to previously defined cockroach allergens. These results are compatible with the hypothesis that microbiome sequences may contribute to the tolerization of T cells for allergen epitopes, and lack of these sequences might conversely be associated with increased likelihood of T cell reactivity against the cockroach epitopes. Taken together this study suggests that microbiome sequence similarity influences immune reactivity to homologous epitopes encoded by pathogens, allergens and auto-antigens.",2018 May 7,"['Carrasco Pro, Sebastian', 'Lindestam Arlehamn, Cecilia S.', 'Dhanda, Sandeep K.', 'Carpenter, Chelsea', 'Lindvall, Mikaela', 'Faruqi, Ali A.', 'Santee, Clark A.', 'Renz, Harald', 'Sidney, John', 'Peters, Bjoern', 'Sette, Alessandro']",PLoS One,,,True
aac4ce5fe242548dc36346e402490ab79dbf1df2,PMC,Impact of confinement housing on study end-points in the calf model of cryptosporidiosis,http://dx.doi.org/10.1371/journal.pntd.0006295,PMC5937795,29694356,CC BY,"BACKGROUND: Diarrhea is the second leading cause of death in children < 5 years globally and the parasite genus Cryptosporidium is a leading cause of that diarrhea. The global disease burden attributable to cryptosporidiosis is substantial and the only approved chemotherapeutic, nitazoxanide, has poor efficacy in HIV positive children. Chemotherapeutic development is dependent on the calf model of cryptosporidiosis, which is the best approximation of human disease. However, the model is not consistently applied across research studies. Data collection commonly occurs using two different methods: Complete Fecal Collection (CFC), which requires use of confinement housing, and Interval Collection (IC), which permits use of box stalls. CFC mimics human challenge model methodology but it is unknown if confinement housing impacts study end-points and if data gathered via this method is suitable for generalization to human populations. METHODS: Using a modified crossover study design we compared CFC and IC and evaluated the impact of housing on study end-points. At birth, calves were randomly assigned to confinement (n = 14) or box stall housing (n = 9), or were challenged with 5 x 10(7) C. parvum oocysts, and followed for 10 days. Study end-points included fecal oocyst shedding, severity of diarrhea, degree of dehydration, and plasma cortisol. FINDINGS: Calves in confinement had no significant differences in mean log oocysts enumerated per gram of fecal dry matter between CFC and IC samples (P = 0.6), nor were there diurnal variations in oocyst shedding (P = 0.1). Confinement housed calves shed significantly more oocysts (P = 0.05), had higher plasma cortisol (P = 0.001), and required more supportive care (P = 0.0009) than calves in box stalls. CONCLUSION: Housing method confounds study end-points in the calf model of cryptosporidiosis. Due to increased stress data collected from calves in confinement housing may not accurately estimate the efficacy of chemotherapeutics targeting C. parvum.",2018 Apr 25,"['Graef, Geneva', 'Hurst, Natalie J.', 'Kidder, Lance', 'Sy, Tracy L.', 'Goodman, Laura B.', 'Preston, Whitney D.', 'Arnold, Samuel L. M.', 'Zambriski, Jennifer A.']",PLoS Negl Trop Dis,,,True
376004b900cd163891128558e6c275dab9ecf34d,PMC,Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV,http://dx.doi.org/10.3389/fmicb.2018.00854,PMC5938362,29765366,CC BY,"Hepatitis C virus (HCV) belongs to the Hepacivirus genus and is genetically heterogeneous, with seven major genotypes further divided into several recognized subtypes. HCV origin was previously dated in a range between ∼200 and 1000 years ago. Hepaciviruses have been identified in several domestic and wild mammals, the largest viral diversity being observed in bats and rodents. The closest relatives of HCV were found in horses/donkeys (equine hepaciviruses, EHV). However, the origin of HCV as a human pathogen is still an unsolved puzzle. Using a selection-informed evolutionary model, we show that the common ancestor of extant HCV genotypes existed at least 3000 years ago (CI: 3192–5221 years ago), with the oldest genotypes being endemic to Asia. EHV originated around 1100 CE (CI: 291–1640 CE). These time estimates exclude that EHV transmission was mainly sustained by widespread veterinary practices and suggest that HCV originated from a single zoonotic event with subsequent diversification in human populations. We also describe a number of biologically important sites in the major HCV genotypes that have been positively selected and indicate that drug resistance-associated variants are significantly enriched at positively selected sites. HCV exploits several cell-surface molecules for cell entry, but only two of these (CD81 and OCLN) determine the species-specificity of infection. Herein evolutionary analyses do not support a long-standing association between primates and hepaciviruses, and signals of positive selection at CD81 were only observed in Chiroptera. No evidence of selection was detected for OCLN in any mammalian order. These results shed light on the origin of HCV and provide a catalog of candidate genetic modulators of HCV phenotypic diversity.",2018 May 1,"['Forni, Diego', 'Cagliani, Rachele', 'Pontremoli, Chiara', 'Pozzoli, Uberto', 'Vertemara, Jacopo', 'De Gioia, Luca', 'Clerici, Mario', 'Sironi, Manuela']",Front Microbiol,,,True
2cbd3c525729a9f2b98e4dbbf7697bb711acd447,PMC,Early events during human coronavirus OC43 entry to the cell,http://dx.doi.org/10.1038/s41598-018-25640-0,PMC5940804,29740099,CC BY,"The Coronaviridae family clusters a number of large RNA viruses, which share several structural and functional features. However, members of this family recognize different cellular receptors and exploit different entry routes, what affects their species specificity and virulence. The aim of this study was to determine how human coronavirus OC43 enters the susceptible cell. Using confocal microscopy and molecular biology tools we visualized early events during infection. We found that the virus employs caveolin-1 dependent endocytosis for the entry and the scission of virus-containing vesicles from the cell surface is dynamin-dependent. Furthermore, the vesicle internalization process requires actin cytoskeleton rearrangements. With our research we strove to broaden the understanding of the infection process, which in future may be beneficial for the development of a potential therapeutics.",2018 May 8,"['Owczarek, Katarzyna', 'Szczepanski, Artur', 'Milewska, Aleksandra', 'Baster, Zbigniew', 'Rajfur, Zenon', 'Sarna, Michal', 'Pyrc, Krzysztof']",Sci Rep,,,False
2410516def70473a479454501fab2cdaf95d88d3,PMC,Early events during human coronavirus OC43 entry to the cell,http://dx.doi.org/10.1038/s41598-018-25640-0,PMC5940804,29740099,CC BY,"The Coronaviridae family clusters a number of large RNA viruses, which share several structural and functional features. However, members of this family recognize different cellular receptors and exploit different entry routes, what affects their species specificity and virulence. The aim of this study was to determine how human coronavirus OC43 enters the susceptible cell. Using confocal microscopy and molecular biology tools we visualized early events during infection. We found that the virus employs caveolin-1 dependent endocytosis for the entry and the scission of virus-containing vesicles from the cell surface is dynamin-dependent. Furthermore, the vesicle internalization process requires actin cytoskeleton rearrangements. With our research we strove to broaden the understanding of the infection process, which in future may be beneficial for the development of a potential therapeutics.",2018 May 8,"['Owczarek, Katarzyna', 'Szczepanski, Artur', 'Milewska, Aleksandra', 'Baster, Zbigniew', 'Rajfur, Zenon', 'Sarna, Michal', 'Pyrc, Krzysztof']",Sci Rep,,,True
6f647c734a4bdf8adc7a70f380483ad7f02ba772,PMC,Differential Regulation of Toll-Like Receptor-Mediated Cytokine Production by Unfolded Protein Response,http://dx.doi.org/10.1155/2018/9827312,PMC5941770,29849928,CC BY,"The ability of the host immune response is largely mediated by the proinflammatory cytokine production. Physiological and pathological conditions of endoplasmic reticulum (ER) trigger unfolded protein response and contribute to the development or pathology of inflammatory diseases. Under ER stress, unfolded protein response (UPR) signaling pathways participate in upregulating inflammatory cytokine production via NF-kappaB, MAPK, and GSK-3β. Moreover, it has been suggested that ER stress crosstalks with toll-like receptor (TLR) signaling pathway to promote the production of proinflammatory cytokines. In addition, TLR stimulation can lead to UPR activation to promote inflammation. In this review, we will cover how proinflammatory cytokine production by UPR signaling can be induced or amplified in the presence or absence of TLR activation.",2018 Apr 24,"['Kim, Sena', 'Joe, Yeonsoo', 'Surh, Young-Joon', 'Chung, Hun Taeg']",Oxid Med Cell Longev,,,True
70c7a787bebc60a3c5e63f7f8409b8be92960964,PMC,Recyclable Keggin Heteropolyacids as an Environmentally Benign Catalyst for the Synthesis of New 2-Benzoylamino-N-phenyl-benzamide Derivatives under Microwave Irradiations at Solvent-Free Conditions and the Evaluation of Biological Activity,http://dx.doi.org/10.3390/molecules23010008,PMC5943967,29267237,CC BY,"2-Benzoylamino-N-phenyl-benzamide derivatives (5a–h) were prepared from 2-phenyl-3,1-(4H)-benzoxazin-4-one 3 and substituted anilines 4a–h in the presence of a Keggin-type heteropolyacids series (H(3)PW(12)O(40)·13H(2)O; H(4)SiW(12)O(40)·13H(2)O; H(4)SiMo(12)O(40)·13H(2)O; and H(3)PMo(12)O(40)·13H(2)O) as catalysts without solvent and under microwave irradiation. We found that the use of H(3)PW(12)O(40)·13H(2)O acid coupled to microwave irradiation allowed obtaining a high-yielding reaction with a short time. The compound structures were established by (1)H-NMR and (13)C-NMR. The antibacterial and antifungal activities of the synthesized compounds exhibited an inhibition of the growth of bacteria and fungi.",2017 Dec 21,"['Ighilahriz-Boubchir, Karima', 'Boutemeur-Kheddis, Baya', 'Rabia, Cherifa', 'Makhloufi-Chebli, Malika', 'Hamdi, Maamar', 'Silva, Artur M. S.']",Molecules,,,True
4b178b4e517e56b75fbe603cfb177e4bf0fd61c4,PMC,Recyclable Keggin Heteropolyacids as an Environmentally Benign Catalyst for the Synthesis of New 2-Benzoylamino-N-phenyl-benzamide Derivatives under Microwave Irradiations at Solvent-Free Conditions and the Evaluation of Biological Activity,http://dx.doi.org/10.3390/molecules23010008,PMC5943967,29267237,CC BY,"2-Benzoylamino-N-phenyl-benzamide derivatives (5a–h) were prepared from 2-phenyl-3,1-(4H)-benzoxazin-4-one 3 and substituted anilines 4a–h in the presence of a Keggin-type heteropolyacids series (H(3)PW(12)O(40)·13H(2)O; H(4)SiW(12)O(40)·13H(2)O; H(4)SiMo(12)O(40)·13H(2)O; and H(3)PMo(12)O(40)·13H(2)O) as catalysts without solvent and under microwave irradiation. We found that the use of H(3)PW(12)O(40)·13H(2)O acid coupled to microwave irradiation allowed obtaining a high-yielding reaction with a short time. The compound structures were established by (1)H-NMR and (13)C-NMR. The antibacterial and antifungal activities of the synthesized compounds exhibited an inhibition of the growth of bacteria and fungi.",2017 Dec 21,"['Ighilahriz-Boubchir, Karima', 'Boutemeur-Kheddis, Baya', 'Rabia, Cherifa', 'Makhloufi-Chebli, Malika', 'Hamdi, Maamar', 'Silva, Artur M. S.']",Molecules,,,False
88c6e8b041b0eceb7b8282f3dbb066848fd554b7,PMC,NLRP3 Inflammasome and Caspase-1/11 Pathway Orchestrate Different Outcomes in the Host Protection Against Trypanosoma cruzi Acute Infection,http://dx.doi.org/10.3389/fimmu.2018.00913,PMC5944318,29774028,CC BY,"Infection with protozoan parasite Trypanosoma cruzi results in activation of nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs). NLR activation leads to inflammasome formation, the activation of caspase-1, and the subsequent cleavage of IL-1β and IL-18. Considering that inflammasome activation and IL-1β induction by macrophages are key players for an appropriate T cell response, we investigated the relevance of NLR pyrin domain-containing 3 (NLRP3) and caspase-1/11 to elucidate their roles in the induction of different T cell phenotypes and the relationship with parasite load and hepatic inflammation during T. cruzi-Tulahuen strain acute infection. We demonstrated that infected nlrp3−/− and C57BL/6 wild type (WT) mice exhibited similar parasitemia and survival, although the parasite load was higher in the livers of nlrp3−/− mice than in those of WT mice. Increased levels of transaminases and pro-inflammatory cytokines were found in the plasma of WT and nlrp3−/− mice indicating that NLRP3 is dispensable to control the parasitemia but it is required for a better clearance of parasites in the liver. Importantly, we have found that NLRP3 and caspase-1/11-deficient mice differentially modulate T helper (Th1, Th2, and Th17) and cytotoxic T lymphocyte phenotypes. Strikingly, caspase-1/11−/− mice showed the most dramatic reduction in the number of IFN-γ- and IL-17-producing CD4+ and CD8+ T cells associated with higher parasitemia and lower survival. Additionally, caspase-1/11−/− mice demonstrated significantly reduced liver inflammation with the lowest alanine aminotransferase (ALT) levels but the highest hepatic parasitic load. These results unequivocally demonstrate that caspase-1/11 pathway plays an important role in the induction of liver adaptive immunity against this parasite infection as well as in hepatic inflammation.",2018 May 3,"['Paroli, Augusto F.', 'Gonzalez, Patricia V.', 'Díaz-Luján, Cintia', 'Onofrio, Luisina I.', 'Arocena, Alfredo', 'Cano, Roxana C.', 'Carrera-Silva, Eugenio A.', 'Gea, Susana']",Front Immunol,,,True
a21809b3622fbd0f1a0ef01eab221fb05ada15e3,PMC,A fatal case associated with respiratory syncytial virus infection in a young child,http://dx.doi.org/10.1186/s12879-018-3123-8,PMC5948794,29751747,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is the most common viral cause of pediatric bronchiolitis and pneumonia worldwide. Risk factors for high mortality and prolonged morbidity after RSV infection include premature birth, bronchopulmonary dysplasia, congenital heart disease, and Down syndrome. However, some previously healthy, full-term children who are infected with RSV also require hospitalization and even experience severe sequelae or death. CASE PRESENTATION: In this report, we present the case of an RSV-associated death of a child who was born at full-term and developed normally up to the age of 2 years old. Cardiopulmonary arrest occurred within 3 days after the onset of symptoms, which included cough and high fever. Complete brain edema was prominent, and encephalopathy was developing. Viral antigen detection and microbiome analyses of oral swab and nasopharyngeal aspirate specimens verified an RSV infection, while bacterial culture of blood specimens yielded negative results. The RSV strain detected in this patient was subtyped as RSVB9, and no mutation was found in the six antigenic sites for targeted drugs or vaccines. CONCLUSIONS: The patient had a severe infection associated with RSV, which was very likely the cause of her central nervous system infection and acute neurological complications.",2018 May 11,"['Xu, Lili', 'Gao, Hengmiao', 'Zeng, Jiansheng', 'Liu, Jun', 'Lu, Cong', 'Guan, Xiaolei', 'Qian, Suyun', 'Xie, Zhengde']",BMC Infect Dis,,,True
5f938778c47463eaa1e15fd63c0656cf830220e3,PMC,Transcriptome Analysis Reveals Dynamic Gene Expression Profiles in Porcine Alveolar Macrophages in Response to the Chinese Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1155/2018/1538127,PMC5949201,29854728,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important swine pathogens and causes reproductive failure in sows and respiratory disease in growing pigs. PRRSV mainly infects porcine alveolar macrophages (PAMs), leading to the subversion of innate and adaptive immunity of pigs. The transcriptome analysis of gene expression profiles in PRRSV-infected PAMs is essential for understanding the pathogenesis of PRRSV. Here we performed next-generation RNA sequencing and a comprehensive bioinformatics analysis to characterize the dynamic transcriptome landscapes in PAMs following PRRSV infection. Totally 38222 annotated mRNAs, 12987 annotated long noncoding RNAs (lncRNAs), and 17624 novel lncRNAs in PRRSV-infected PAMs were identified through a transcripts computational identification pipeline. The differentially expressed mRNAs and lncRNAs during PRRSV infection were characterized. Several differentially expressed transcripts were validated using qRT-PCR. Analyses on dynamic overrepresented GO terms and KEGG pathways in PRRSV-infected PAMs at different time points were performed. Meanwhile the genes involved in IFN-related signaling pathways, proinflammatory cytokines and chemokines, phagocytosis, and antigen presentation and processing were significantly downregulated, indicating the aberrant function of PAMs during PRRSV infection. Moreover, the differentially and highly expressed lncRNA XR_297549.1 was predicted to both cis-regulate and trans-regulate its neighboring gene, prostaglandin-endoperoxide synthase 2 (PTGS2), indicating its role in inflammatory response. Our findings reveal the transcriptome profiles and differentially expressed mRNAs and lncRNAs in PRRSV-infected PAMs in vitro, providing valuable information for further exploration of PRRSV pathogenesis.",2018 Apr 29,"['Zeng, Nanfang', 'Wang, Cong', 'Liu, Siyu', 'Miao, Qi', 'Zhou, Lei', 'Ge, Xinna', 'Han, Jun', 'Guo, Xin', 'Yang, Hanchun']",Biomed Res Int,,,True
bee209540848ded10add285c6a2d90906961baea,PMC,Immortalized common marmoset (Callithrix jacchus) hepatic progenitor cells possess bipotentiality in vitro and in vivo,http://dx.doi.org/10.1038/s41421-018-0020-7,PMC5951880,29796307,CC BY,"Common marmoset (Callithrix jacchus) is emerging as a clinically relevant nonhuman primate model for various diseases, but is hindered by the availability of marmoset cell lines, which are critical for understanding the disease pathogenesis and drug/toxicological screening prior to animal testing. Here we describe the generation of immortalized marmoset hepatic progenitor cells (MHPCs) by lentivirus-mediated transfer of the simian virus 40 large T antigen gene in fetal liver polygonal cells. MHPCs proliferate indefinitely in vitro without chromosomal alteration and telomere shortening. These cells possess hepatic progenitor cell-specific gene expression profiles with potential to differentiate into both hepatocytic and cholangiocytic lineages in vitro and in vivo and also can be genetically modified. Importantly, injected MHPCs repopulated the injured liver of fumarylacetoacetate hydrolase (Fah)-deficient mice with hepatocyte-like cells. MHPCs also engraft as cholangiocytes into bile ducts of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced bile ductular injured mice. MHPCs provide a tool to enable efficient derivation and genetic modification of both hepatocytes and cholangiocytes for use in disease modeling, tissue engineering, and drug screening.",2018 May 15,"['Guo, Zhenglong', 'Jing, Renwei', 'Rao, Quan', 'Zhang, Ludi', 'Gao, Yimeng', 'Liu, Fengyong', 'Wang, Xin', 'Hui, Lijian', 'Yin, HaiFang']",Cell Discov,,,True
715063d01372186739566d9c343b16ebb45f32eb,PMC,Novel canine circovirus strains from Thailand: Evidence for genetic recombination,http://dx.doi.org/10.1038/s41598-018-25936-1,PMC5951951,29760429,CC BY,"Canine circoviruses (CanineCV’s), belonging to the genus Circovirus of the Circoviridae family, were detected by next generation sequencing in samples from Thai dogs with respiratory symptoms. Genetic characterization and phylogenetic analysis of nearly complete CanineCV genomes suggested that natural recombination had occurred among different lineages of CanineCV’s. Similarity plot and bootscaning analyses indicated that American and Chinese viruses had served as major and minor parental viruses, respectively. Positions of recombination breakpoints were estimated using maximum-likelihood frameworks with statistical significant testing. The putative recombination event was located in the Replicase gene, intersecting with open reading frame-3. Analysis of nucleotide changes confirmed the origin of the recombination event. This is the first description of naturally occurring recombinant CanineCV’s that have resulted in the circulation of newly emerging CanineCV lineages.",2018 May 14,"['Piewbang, Chutchai', 'Jo, Wendy K.', 'Puff, Christina', 'van der Vries, Erhard', 'Kesdangsakonwut, Sawang', 'Rungsipipat, Anudep', 'Kruppa, Jochen', 'Jung, Klaus', 'Baumgärtner, Wolfgang', 'Techangamsuwan, Somporn', 'Ludlow, Martin', 'Osterhaus, Albert D. M. E.']",Sci Rep,,,True
e142106dccc14c30910e705e1159d340c6a97832,PMC,Development of a Broadly Accessible Venezuelan Equine Encephalitis Virus Replicon Particle Vaccine Platform,http://dx.doi.org/10.1128/JVI.00027-18,PMC5952155,29540599,CC BY,"Zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. Portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. In this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated Venezuelan equine encephalitis (VEE) virus vaccine, strain 3526 (VRP 3526). Using both noroviruses and coronaviruses as model systems, we demonstrate the utility of the VRP 3526 platform in the generation of recombinant proteins, production of virus-like particles, and in vivo efficacy as a vaccine against emergent viruses. Importantly, packaging under biosafety level 2 (BSL2) conditions distinguishes VRP 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of laboratories around the world. In addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to that of previously attenuated VRP approaches. Taking these results together, the VRP 3526 platform represents a safe and highly portable system that can be rapidly deployed under BSL2 conditions for generation of candidate vaccines against emerging microbial pathogens. IMPORTANCE While VEE virus replicon particles provide a robust, established platform for antigen expression and vaccination, its utility has been limited by the requirement for high-containment-level facilities for production and packaging. In this work, we utilize an attenuated vaccine strain capable of use at lower biocontainment level but retaining the capacity of the wild-type replicon particle. Importantly, the new replicon platform provides equal protection for aged mice and following heterologous challenge, which distinguishes it from other attenuated replicon platforms. Together, the new system represents a highly portable, safe system for use in the context of disease emergence.",2018 May 14,"['Agnihothram, Sudhakar', 'Menachery, Vineet D.', 'Yount, Boyd L.', 'Lindesmith, Lisa C.', 'Scobey, Trevor', 'Whitmore, Alan', 'Schäfer, Alexandra', 'Heise, Mark T.', 'Baric, Ralph S.']",J Virol,,,True
c482f885d7100665959d0e8a2e97d940cc4c6961,PMC,Recent advances in the understanding and management of cystic fibrosis pulmonary exacerbations,http://dx.doi.org/10.12688/f1000research.13926.1,PMC5954331,29862015,CC BY,"Pulmonary exacerbations are common events in cystic fibrosis and have a profound impact on quality of life, morbidity, and mortality. Pulmonary exacerbation outcomes remain poor and a significant proportion of patients fail to recover their baseline lung function despite receiving aggressive treatment with intravenous antibiotics. This focused review provides an update on some of the recent advances that have taken place in our understanding of the epidemiology, pathophysiology, diagnosis, and management of pulmonary exacerbations in cystic fibrosis as well as direction for future study.",2018 May 14,"['Skolnik, Kate', 'Quon, Bradley S.']",F1000Res,,,True
5938b0be5d7696d37c227bc647bcbc3f7f3ae18b,PMC,Development of a cell-based assay to identify hepatitis B virus entry inhibitors targeting the sodium taurocholate cotransporting polypeptide,http://dx.doi.org/10.18632/oncotarget.25348,PMC5955094,29805766,CC BY,"Sodium taurocholate cotransporting polypeptide (NTCP) is a major entry receptor of hepatitis B virus (HBV) and one of the most attractive targets for anti-HBV drugs. We developed a cell-mediated drug screening method to monitor NTCP expression on the cell surface by generating a HepG2 cell line with tetracycline-inducible expression of NTCP and a monoclonal antibody that specifically detects cell-surface NTCP. Using this system, we screened a small molecule library for compounds that protected against HBV infection by targeting NTCP. We found that glabridin, a licorice-derived isoflavane, could suppress viral infection by inducing caveolar endocytosis of cell-surface NTCP with an IC(50) of ~40 μM. We also found that glabridin could attenuate the inhibitory effect of taurocholate on type I interferon signaling by depleting the level of cell-surface NTCP. These results demonstrate that our screening system could be a powerful tool for discovering drugs targeting HBV entry.",2018 May 4,"['Miyakawa, Kei', 'Matsunaga, Satoko', 'Yamaoka, Yutaro', 'Dairaku, Mina', 'Fukano, Kento', 'Kimura, Hirokazu', 'Chimuro, Tomoyuki', 'Nishitsuji, Hironori', 'Watashi, Koichi', 'Shimotohno, Kunitada', 'Wakita, Takaji', 'Ryo, Akihide']",Oncotarget,,,True
9f88a88a26c8432f7c3dea1a2f8d1b330a559d48,PMC,Development of a cell-based assay to identify hepatitis B virus entry inhibitors targeting the sodium taurocholate cotransporting polypeptide,http://dx.doi.org/10.18632/oncotarget.25348,PMC5955094,29805766,CC BY,"Sodium taurocholate cotransporting polypeptide (NTCP) is a major entry receptor of hepatitis B virus (HBV) and one of the most attractive targets for anti-HBV drugs. We developed a cell-mediated drug screening method to monitor NTCP expression on the cell surface by generating a HepG2 cell line with tetracycline-inducible expression of NTCP and a monoclonal antibody that specifically detects cell-surface NTCP. Using this system, we screened a small molecule library for compounds that protected against HBV infection by targeting NTCP. We found that glabridin, a licorice-derived isoflavane, could suppress viral infection by inducing caveolar endocytosis of cell-surface NTCP with an IC(50) of ~40 μM. We also found that glabridin could attenuate the inhibitory effect of taurocholate on type I interferon signaling by depleting the level of cell-surface NTCP. These results demonstrate that our screening system could be a powerful tool for discovering drugs targeting HBV entry.",2018 May 4,"['Miyakawa, Kei', 'Matsunaga, Satoko', 'Yamaoka, Yutaro', 'Dairaku, Mina', 'Fukano, Kento', 'Kimura, Hirokazu', 'Chimuro, Tomoyuki', 'Nishitsuji, Hironori', 'Watashi, Koichi', 'Shimotohno, Kunitada', 'Wakita, Takaji', 'Ryo, Akihide']",Oncotarget,,,False
2094652c2eeb8a55eee12afad81cb3ecb86a2bcf,PMC,Selective inhibition of host cell signaling for rotavirus antivirals: PI3K/Akt/mTOR-mediated rotavirus pathogenesis,http://dx.doi.org/10.1080/21505594.2017.1356539,PMC5955445,28723236,CC BY,,2017 Aug 18,"Kindrachuk, Jason",Virulence,,,True
485b745f048cbac696175c1ca05eee8fb46ba026,PMC,PI3K-Akt-mTOR axis sustains rotavirus infection via the 4E-BP1 mediated autophagy pathway and represents an antiviral target,http://dx.doi.org/10.1080/21505594.2017.1326443,PMC5955461,28475412,CC BY,"Rotavirus infection is a major cause of severe dehydrating diarrhea in infants younger than 5 y old and in particular cases of immunocompromised patients irrespective to the age of the patients. Although vaccines have been developed, antiviral therapy is an important complement that cannot be substituted. Because of the lack of specific approved treatment, it is urgent to facilitate the cascade of further understanding of the infection biology, identification of druggable targets and the final development of effective antiviral therapies. PI3K-Akt-mTOR signaling pathway plays a vital role in regulating the infection course of many viruses. In this study, we have dissected the effects of PI3K-Akt-mTOR signaling pathway on rotavirus infection using both conventional cell culture models and a 3D model of human primary intestinal organoids. We found that PI3K-Akt-mTOR signaling is essential in sustaining rotavirus infection. Thus, blocking the key elements of this pathway, including PI3K, mTOR and 4E-BP1, has resulted in potent anti-rotavirus activity. Importantly, a clinically used mTOR inhibitor, rapamycin, potently inhibited both experimental and patient-derived rotavirus strains. This effect involves 4E-BP1 mediated induction of autophagy, which in turn exerts anti-rotavirus effects. These results revealed new insights on rotavirus-host interactions and provided new avenues for antiviral drug development.",2017 Jun 1,"['Yin, Yuebang', 'Dang, Wen', 'Zhou, Xinying', 'Xu, Lei', 'Wang, Wenshi', 'Cao, Wanlu', 'Chen, Sunrui', 'Su, Junhong', 'Cai, Xuepeng', 'Xiao, Shaobo', 'Peppelenbosch, Maikel P.', 'Pan, Qiuwei']",Virulence,,,True
f72f4443be3e73ec7e6e37ae426caaf5a4924abe,PMC,Lactobacillus Mucosal Vaccine Vectors: Immune Responses against Bacterial and Viral Antigens,http://dx.doi.org/10.1128/mSphere.00061-18,PMC5956152,29769376,CC BY,"Lactic acid bacteria (LAB) have been utilized since the 1990s for therapeutic heterologous gene expression. The ability of LAB to elicit an immune response against expressed foreign antigens has led to their exploration as potential mucosal vaccine candidates. LAB vaccine vectors offer many attractive advantages: simple, noninvasive administration (usually oral or intranasal), the acceptance and stability of genetic modifications, relatively low cost, and the highest level of safety possible. Experimentation using LAB of the genus Lactobacillus has become popular in recent years due to their ability to elicit strong systemic and mucosal immune responses. This article reviews Lactobacillus vaccine constructs, including Lactobacillus species, antigen expression, model organisms, and in vivo immune responses, with a primary focus on viral and bacterial antigens.",2018 May 16,"['LeCureux, Jonathan S.', 'Dean, Gregg A.']",mSphere,,,True
ea538974071c2e340580098fe6ea6998654c1fcb,PMC,"Screening of melatonin, α-tocopherol, folic acid, acetyl-l-carnitine and resveratrol for anti-dengue 2 virus activity",http://dx.doi.org/10.1186/s13104-018-3417-3,PMC5956857,29769094,CC BY,"OBJECTIVE: Infections with the mosquito transmitted dengue virus (DENV) are a significant public health burden in many parts of the world. Despite the introduction of a commercial vaccine in some parts of the world, the majority of the populations at risk of infection remain unprotected against this disease, and there is currently no treatment for DENV infection. Natural compounds offer the prospect of cheap and sustainable therapeutics to reduce the disease burden during infection, and thus potentially alleviate the risk of more severe disease. This study evaluated the potential anti-DENV 2 activity of five natural compounds namely melatonin, α-tocopherol, folic acid, acetyl-l-carnitine and resveratrol in two different cell lines. RESULTS: Screening of the compounds showed that one compound (acetyl-l-carnitine) showed no effect on DENV infection, three compounds (melatonin, α-tocopherol and folic acid) slightly increased levels of infection, while the 5th compound, resveratrol, showed some limited anti-DENV activity, with resveratrol reducing virus output with an EC(50) of less than 25 μM. These results suggest that some commonly taken natural compounds may have beneficial effects on DENV infection, but that others may potentially add to the disease burden. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-018-3417-3) contains supplementary material, which is available to authorized users.",2018 May 16,"['Paemanee, Atchara', 'Hitakarun, Atitaya', 'Roytrakul, Sittiruk', 'Smith, Duncan R.']",BMC Res Notes,,,False
ccd7c227d302eb3c2dc1a24bb9aa6c1acee2812b,PMC,"Screening of melatonin, α-tocopherol, folic acid, acetyl-l-carnitine and resveratrol for anti-dengue 2 virus activity",http://dx.doi.org/10.1186/s13104-018-3417-3,PMC5956857,29769094,CC BY,"OBJECTIVE: Infections with the mosquito transmitted dengue virus (DENV) are a significant public health burden in many parts of the world. Despite the introduction of a commercial vaccine in some parts of the world, the majority of the populations at risk of infection remain unprotected against this disease, and there is currently no treatment for DENV infection. Natural compounds offer the prospect of cheap and sustainable therapeutics to reduce the disease burden during infection, and thus potentially alleviate the risk of more severe disease. This study evaluated the potential anti-DENV 2 activity of five natural compounds namely melatonin, α-tocopherol, folic acid, acetyl-l-carnitine and resveratrol in two different cell lines. RESULTS: Screening of the compounds showed that one compound (acetyl-l-carnitine) showed no effect on DENV infection, three compounds (melatonin, α-tocopherol and folic acid) slightly increased levels of infection, while the 5th compound, resveratrol, showed some limited anti-DENV activity, with resveratrol reducing virus output with an EC(50) of less than 25 μM. These results suggest that some commonly taken natural compounds may have beneficial effects on DENV infection, but that others may potentially add to the disease burden. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-018-3417-3) contains supplementary material, which is available to authorized users.",2018 May 16,"['Paemanee, Atchara', 'Hitakarun, Atitaya', 'Roytrakul, Sittiruk', 'Smith, Duncan R.']",BMC Res Notes,,,False
bc7b16d381d2acf67eb97db19f1686c90d72ecf1,PMC,"Screening of melatonin, α-tocopherol, folic acid, acetyl-l-carnitine and resveratrol for anti-dengue 2 virus activity",http://dx.doi.org/10.1186/s13104-018-3417-3,PMC5956857,29769094,CC BY,"OBJECTIVE: Infections with the mosquito transmitted dengue virus (DENV) are a significant public health burden in many parts of the world. Despite the introduction of a commercial vaccine in some parts of the world, the majority of the populations at risk of infection remain unprotected against this disease, and there is currently no treatment for DENV infection. Natural compounds offer the prospect of cheap and sustainable therapeutics to reduce the disease burden during infection, and thus potentially alleviate the risk of more severe disease. This study evaluated the potential anti-DENV 2 activity of five natural compounds namely melatonin, α-tocopherol, folic acid, acetyl-l-carnitine and resveratrol in two different cell lines. RESULTS: Screening of the compounds showed that one compound (acetyl-l-carnitine) showed no effect on DENV infection, three compounds (melatonin, α-tocopherol and folic acid) slightly increased levels of infection, while the 5th compound, resveratrol, showed some limited anti-DENV activity, with resveratrol reducing virus output with an EC(50) of less than 25 μM. These results suggest that some commonly taken natural compounds may have beneficial effects on DENV infection, but that others may potentially add to the disease burden. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-018-3417-3) contains supplementary material, which is available to authorized users.",2018 May 16,"['Paemanee, Atchara', 'Hitakarun, Atitaya', 'Roytrakul, Sittiruk', 'Smith, Duncan R.']",BMC Res Notes,,,True
57a8f6955709acb05304154c9863ca79f6a5c1b0,PMC,Securitizing HIV/AIDS: a game changer in state-societal relations in China?,http://dx.doi.org/10.1186/s12992-018-0364-7,PMC5956947,29769102,CC BY,"BACKGROUND: China has experienced unprecedented economic growth since the 1980s. Despite this impressive economic development, this growth exists side by side with the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and severe acute respiratory syndrome (SARS) crises and the persisting deficiencies in public health provision in China. Acknowledging the prevailing health problems, the Chinese government has encouraged the development of health non-governmental organizations (NGOs) to respond to the health challenges and address the gaps in public health provision of the government. HIV/AIDS-focused NGOs have been perceived as the most outstanding civil society group developed in China. Considering the low priority of health policies since the economic reform, the limitation of the “third sector” activity permitted in authoritarian China, together with the political sensitivity of the HIV/AIDS problem in the country, this article aims to explain the proliferation of HIV/AIDS-focused NGOs in China with the usage of the securitization framework in the field of international relations (IR). METHODS: The research that underpins this article is based on a desk-based literature review as well as in-depth field interviews with individuals working in HIV/AIDS-focused NGOs in China. Face-to-face interviews for this research were conducted between January and May in 2011, and between December 2016 and January 2017, in China. Discourse analysis was in particular employed in the study of the security-threat framing process (securitization) of HIV/AIDS in China. RESULTS: This article argues that the proliferation of HIV/AIDS-related NGOs in China is largely attributed to the normative and technical effects of HIV/AIDS securitization ushered in by the United Nations Security Council (UNSC) and supported by the Global Fund to Fight AIDS, Tuberculosis, and Malaria (hereinafter Global Fund) observed in China. Despite depicting a positive scenario, the development of HIV/AIDS-focused NGOs in China generated by the international securitization efforts is largely limited. An internal and external factor was identified to verify the argument, namely (1) the reduction of international financial commitments, as well as (2) the fragmentation of HIV/AIDS-focused NGO community in China. CONCLUSIONS: This article shows that international securitization weakened with the rise of Chinese commitment on HIV/AIDS interventions. In other words, HIV/AIDS-related responses delivered by the national government are no longer checked by the global mechanism of HIV/AIDS; thus it is unclear whether these NGOs would remain of interest as partners for the government. The fragmentation of the HIV/AIDS community would further hinder the development, preventing from NGOs with the same interest forming alliances to call for changes in current political environment. Such restriction on the concerted efforts of HIV/AIDS-related NGOs in China would make achievement of the Sustainable Development Goals (SDGs) to foster stronger partnerships between the government and civil society difficult, which in turn hindering the realization of ending HIV/AIDS in the world by 2030.",2018 May 16,"Lo, Catherine Yuk-ping",Global Health,,,True
96fc4a051f2ecc366f49ca34902324d059577798,PMC,Progression of the Radiologic Severity Index predicts mortality in patients with parainfluenza virus-associated lower respiratory infections,http://dx.doi.org/10.1371/journal.pone.0197418,PMC5957350,29771962,CC BY,"BACKGROUND: Radiologic severity may predict adverse outcomes after lower respiratory tract infection (LRI). However, few studies have quantified radiologic severity of LRIs. We sought to evaluate whether a semi-quantitative scoring tool, the Radiologic Severity Index (RSI), predicted mortality after parainfluenza virus (PIV)-associated LRI. METHODS: We conducted a retrospective review of consecutively-enrolled adult patients with hematologic malignancy or hematopoietic stem cell transplantation and with PIV detected in nasal wash who subsequently developed radiologically-confirmed LRI. We measured RSI (range 0–72) in each chest radiograph during the first 30 days after LRI diagnosis. We used extended Cox proportional hazards models to identify factors associated with mortality after onset of LRI with all-cause mortality as our failure event. RESULTS: After adjustment for patient characteristics, each 1-point increase in RSI was associated with an increased hazard of death (HR 1.13, 95% confidence interval [CI] 1.05–1.21, p = 0.0008). Baseline RSI was not predictive of death, but both peak RSI and the change from baseline to peak RSI (delta-RSI) predicted mortality (odds ratio for mortality, peak: 1.11 [95%CI 1.04–1.18], delta-RSI: 1.14 [95%CI 1.06–1.22]). A delta-RSI of ≥19.5 was 89% sensitive and 91% specific in predicting 30-day mortality. CONCLUSIONS: We conclude that the RSI offers precise, informative and reliable assessments of LRI severity. Progression of RSI predicts 30-day mortality after LRI, but baseline RSI does not. Our results were derived from a cohort of patients with PIV-associated LRI, but can be applied in validated in other populations of patients with LRI.",2018 May 17,"['Sheshadri, Ajay', 'Shah, Dimpy P.', 'Godoy, Myrna', 'Erasmus, Jeremy J.', 'Song, Juhee', 'Li, Liang', 'Evans, Scott E.', 'Chemaly, Roy F.', 'Dickey, Burton F.', 'Ost, David E.']",PLoS One,,,True
1e39b7b66d19b0beaf607a0ea98ea1d13c402ad9,PMC,The Network of Interactions Among Porcine Reproductive and Respiratory Syndrome Virus Non-structural Proteins,http://dx.doi.org/10.3389/fmicb.2018.00970,PMC5960727,29867873,CC BY,"The RNA synthesis of porcine reproductive and respiratory syndrome virus (PRRSV), a positive-strand RNA virus, is compartmentalized in virus-induced double-membrane vesicles where viral proteins and some cellular proteins assemble into replication and transcription complexes (RTCs). The viral replicase proteins are the major components of the RTCs but the physical associations among these non-structural proteins (nsps) remain elusive. In this study, we investigated the potential interactions between PRRSV nsps by yeast two-hybrid (Y2H), bimolecular fluorescence complementation (BiFC) and pull-down assays. Our analyses revealed a complex network of interactions involving most of PRRSV nsps. Among them, nsp9 and nsp12 were identified as the hubs of the nsp interactome; transmembrane proteins nsp2 and nsp5 both interacted with nsp3, indicating that the three membrane-bound proteins might bind together to form the scaffold to support the association of RTCs with the intracellular membrane. The PRRSV nsp interactions identified in this study may provide valuable clues for future researches on the RTC formation and function.",2018 May 14,"['Nan, Hao', 'Lan, Jixun', 'Tian, Mengmeng', 'Dong, Shan', 'Tian, Jiao', 'Liu, Long', 'Xu, Xiaodong', 'Chen, Hongying']",Front Microbiol,,,True
5adf1ce218579cf9f0f919c778c05bf0f864c1a5,PMC,High Level Antibody Response to Pandemic Influenza H1N1/09 Virus Is Associated With Interferon-Induced Transmembrane Protein-3 rs12252-CC in Young Adults,http://dx.doi.org/10.3389/fcimb.2018.00134,PMC5962690,29868492,CC BY,"Background: The C allele of the interferon-induced transmembrane protein-3 (IFITM3) SNP rs12252, a common allele in South East Asia and China, is strongly associated with severe influenza infection. However, despite the high occurrence of rs12252-CC genotype in Chinese population (~25%), severe influenza infection is rare. The aim of study is to determine whether rs12252-CC individuals have pre-existing antibody responses to previous seasonal influenza infections. Cohort and Method: A total 99 young healthy volunteers (18–20 years) were recruited and received an influenza seasonal Vaccination [A/Switzerland/9715293/2013(H3N2), A/California/7/2009 (pdm09H1N1) and B/Jeep/3073/2013-like virus (Flu-B)]. Plasma and gDNA was isolated from each volunteer before, and 14, 28, 180, 360, and 540 days after vaccination. Additionally, 68 elderlies (>65 years) were also recruited as a control group to compare the levels of antibodies at baseline between the young adults and the elderly. For each sample IFITM3 rs12252 genotype was determined and antibody levels in response to pdmH1N1, H3N2 and Influenza B infection were measured for each time point. Results: We found a significantly higher level of pre-existing antibodies to pandemic influenza H1N1/09 virus (pdm09H1N1) but not to H3N2 or FluB in CC donors in comparison with CT/TT donors prior to vaccination. No impact of IFITM3 genotype in boosting influenza specific antibodies in young adults within 1 year after receiving seasonal influenza vaccination was observed. In addition, there was no difference in pdm09H1N1 specific antibody levels observed in the elderly cohort between volunteers carrying different IFITM3 genotypes. Higher levels of antibodies to pdmH1N1 were observed in elderly CC carriers when compared to the young CC carriers, but this trend was not replicated in TT carriers. Conclusion: IFITM3-rs12252 CC carriers exhibit a high level of pre-existing immunity to pdm09H1N1 compared to TT carriers in the young cohort. This suggests that compensatory mechanisms exist which might contribute to viral control in patients carrying the rs12252-CC genotype who do not become sick after flu infection. However, such a potential compensatory effect appears to be lost overtime, as evidenced in the elderly cohort. If this compensatory mechanism is lost, it may make the CC carrying elderly more susceptible to severe influenza infection.",2018 May 15,"['Qin, Ling', 'Wang, Dayan', 'Li, Dongfu', 'Zhao, Yan', 'Peng, Yanchun', 'Wellington, Dannielle', 'Dai, Yanchao', 'Sun, Huanqin', 'Sun, Jinping', 'Liu, Guihai', 'McMichael, Andrew', 'Dong, Tao', 'Zhang, Yonghong']",Front Cell Infect Microbiol,,,True
fc83785220bddefb3ae13e33fc3a49f9290cdc84,PMC,Tonsillar cytokine expression between patients with tonsillar hypertrophy and recurrent tonsillitis,http://dx.doi.org/10.1186/s13601-018-0205-z,PMC5963068,29942488,CC BY,"BACKGROUND: Tonsils provide an innovative in vivo model for investigating immune response to infections and allergens. However, data are scarce on the differences in tonsillar virus infections and immune responses between patients with tonsillar hypertrophy or recurrent tonsillitis. We investigated the differences in virus detection and T cell and interferon gene expression in patients undergoing tonsillectomy due to tonsillar hypertrophy or recurrent tonsillitis. METHODS: Tonsils of 89 surgical patients with tonsillar hypertrophy (n = 47) or recurrent tonsillitis (n = 42) were analysed. Patients were carefully characterized clinically. Standard questionnaire was used to asses preceding and allergy symptoms. Respiratory viruses were analysed in tonsils and nasopharynx by PCR. Quantitative real-time PCR was used to analyse intratonsillar gene expressions of IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2 and Tbet. RESULTS: Median age of the subjects was 15 years (range 2–60). Patients with tonsillar hypertrophy were younger, smoked less often, had less pollen allergy and had more adenovirus, bocavirus-1, coronavirus and rhinovirus in nasopharynx (all P < 0.05). Only bocavirus-1 was more often detected in hypertrophic tonsils (P < 0.05). In age-adjusted analysis, tonsillar hypertrophy was associated with higher mRNA expressions of IL-37 (P < 0.05). CONCLUSIONS: Intratonsillar T cell and interferon gene expressions appeared to be relatively stable for both tonsillar hypertrophy and recurrent tonsillitis. Of the studied cytokines, only newly discovered anti-inflammatory cytokine IL-37, was independently associated with tonsillar hypertrophy showing slightly stronger anti-inflammatory response in these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13601-018-0205-z) contains supplementary material, which is available to authorized users.",2018 May 22,"['Mikola, Emilia', 'Elenius, Varpu', 'Saarinen, Maria', 'Palomares, Oscar', 'Waris, Matti', 'Turunen, Riitta', 'Puhakka, Tuomo', 'Ivaska, Lotta', 'Rückert, Beate', 'Aab, Alar', 'Vahlberg, Tero', 'Vuorinen, Tytti', 'Allander, Tobias', 'Camargo, Carlos A.', 'Akdis, Mübeccel', 'Akdis, Cezmi A.', 'Jartti, Tuomas']",Clin Transl Allergy,,,True
46e6c155f1b7e6d93735e45da3f93b0f1ae63113,PMC,"Occupational infection and needle stick injury among clinical laboratory workers in Al-Madinah city, Saudi Arabia",http://dx.doi.org/10.1186/s12995-018-0198-5,PMC5963129,29942343,CC BY,"BACKGROUND: Clinical laboratory workers face biohazard such as needlestick injury and occupational infection on a daily basis. In this study, we examined self-reported frequency of occupational infection and needlestick injury among the clinical laboratory workers in Al- Madinah, Saudi Arabia. METHODS: A total of 234 clinical laboratory workers were recruited from private and government health sectors to answer a self-administered questionnaire that was prepared to achieve the aims of the study. RESULTS: The results showed that approximately 33% of the sample had an experienced occupational infection while 24% had experienced a needlestick injury. Approximately, 49% reported that they always recap needle after use, whereas 15% reported doing that most of the times. Occupational infection, needlestick injury and recapping needles after use were associated with lack of training on biosafety (P < 0.05). CONCLUSION: The frequency of occupational infection and needlestick injury among clinical laboratory workers in Al-Madinah is high. Interventions related to biosafety and infection control and the use of needlestick prevention devices might be useful in lowering such frequency.",2018 May 21,"['Khabour, Omar F.', 'Al Ali, Khalil H.', 'Mahallawi, Waleed H.']",J Occup Med Toxicol,,,True
9e115f050e9a4bfa777fcbf79204014270383274,PMC,Anti-oxidant and Anti-Inflammatory Cyclic Diarylheptanoids from Alnus japonica Stem Bark,,PMC5963649,29844779,CC BY,"A new cyclic diarylheptanoid namely alnuheptanoid B (3), along with four known cyclic diarylheptanoids: myricanone (1), (+)-S-myricanol (2), myricanone 5-O- -D-glucopyranoside (4), and (+)-S-myricanol 5-O- -D-glucopyranoside (5) were isolated from the EtOAc fraction of Alnus japonica Steud (family: Betulaceae) stem bark. Their structures were established by different spectroscopic analyses, as well as optical rotation measurement. Compounds 1, 2, 4, and 5 are isolated for the first time from A. japonica. The antioxidant and anti-inflammatory activities of compounds (1-5) were assessed using DPPH assay and carrageenin induced rat paw edema model, respectively. They displayed significant antioxidant activity in relation to propyl gallate (standard antioxidant) at concentration 50 µM. Compound 2 demonstrated anti-inflammatory effect at a dose 10 mg/kg compared with indomethacin (positive control).",2017 Winter,"['R.M. Ibrahim, Sabrin', 'A. Mohamed, Gamal', 'I. M. Khedr, Amgad', 'M. Aljaeid, Bader']",Iran J Pharm Res,,,True
bfbb1dddd2a6d304edf8c9cf1086613210f4a8f6,PMC,"Role of Severe Acute Respiratory Syndrome Coronavirus Viroporins E, 3a, and 8a in Replication and Pathogenesis",http://dx.doi.org/10.1128/mBio.02325-17,PMC5964350,29789363,CC BY,"Viroporins are viral proteins with ion channel (IC) activity that play an important role in several processes, including virus replication and pathogenesis. While many coronaviruses (CoVs) encode two viroporins, severe acute respiratory syndrome CoV (SARS-CoV) encodes three: proteins 3a, E, and 8a. Additionally, proteins 3a and E have a PDZ-binding motif (PBM), which can potentially bind over 400 cellular proteins which contain a PDZ domain, making them potentially important for the control of cell function. In the present work, a comparative study of the functional motifs included within the SARS-CoV viroporins was performed, mostly focusing on the roles of the IC and PBM of E and 3a proteins. Our results showed that the full-length E and 3a proteins were required for maximal SARS-CoV replication and virulence, whereas viroporin 8a had only a minor impact on these activities. A virus missing both the E and 3a proteins was not viable, whereas the presence of either protein with a functional PBM restored virus viability. E protein IC activity and the presence of its PBM were necessary for virulence in mice. In contrast, the presence or absence of the homologous motifs in protein 3a did not influence virus pathogenicity. Therefore, dominance of the IC and PBM of protein E over those of protein 3a was demonstrated in the induction of pathogenesis in mice.",2018 May 22,"['Castaño-Rodriguez, Carlos', 'Honrubia, Jose M.', 'Gutiérrez-Álvarez, Javier', 'DeDiego, Marta L.', 'Nieto-Torres, Jose L.', 'Jimenez-Guardeño, Jose M.', 'Regla-Nava, Jose A.', 'Fernandez-Delgado, Raul', 'Verdia-Báguena, Carmina', 'Queralt-Martín, Maria', 'Kochan, Grazyna', 'Perlman, Stanley', 'Aguilella, Vicente M.', 'Sola, Isabel', 'Enjuanes, Luis']",mBio,,,True
bd05c37d7f0fe6c8ba93e2a5cbc52ac371a8fbce,PMC,Bat Caliciviruses and Human Noroviruses Are Antigenically Similar and Have Overlapping Histo-Blood Group Antigen Binding Profiles,http://dx.doi.org/10.1128/mBio.00869-18,PMC5964351,29789360,CC BY,"Emerging zoonotic viral diseases remain a challenge to global public health. Recent surveillance studies have implicated bats as potential reservoirs for a number of viral pathogens, including coronaviruses and Ebola viruses. Caliciviridae represent a major viral family contributing to emerging diseases in both human and animal populations and have been recently identified in bats. In this study, we blended metagenomics, phylogenetics, homology modeling, and in vitro assays to characterize two novel bat calicivirus (BtCalV) capsid sequences, corresponding to strain BtCalV/A10/USA/2009, identified in Perimyotis subflavus near Little Orleans, MD, and bat norovirus. We observed that bat norovirus formed virus-like particles and had epitopes and receptor-binding patterns similar to those of human noroviruses. To determine whether these observations stretch across multiple bat caliciviruses, we characterized a novel bat calicivirus, BtCalV/A10/USA/2009. Phylogenetic analysis revealed that BtCalV/A10/USA/2009 likely represents a novel Caliciviridae genus and is most closely related to ""recoviruses."" Homology modeling revealed that the capsid sequences of BtCalV/A10/USA/2009 and bat norovirus resembled human norovirus capsid sequences and retained host ligand binding within the receptor-binding domains similar to that seen with human noroviruses. Both caliciviruses bound histo-blood group antigens in patterns that overlapped those seen with human and animal noroviruses. Taken together, our results indicate the potential for bat caliciviruses to bind histo-blood group antigens and overcome a significant barrier to cross-species transmission. Additionally, we have shown that bat norovirus maintains antigenic epitopes similar to those seen with human noroviruses, providing further evidence of evolutionary descent. Our results reiterate the importance of surveillance of wild-animal populations, especially of bats, for novel viral pathogens.",2018 May 22,"['Kocher, Jacob F.', 'Lindesmith, Lisa C.', 'Debbink, Kari', 'Beall, Anne', 'Mallory, Michael L.', 'Yount, Boyd L.', 'Graham, Rachel L.', 'Huynh, Jeremy', 'Gates, J. Edward', 'Donaldson, Eric F.', 'Baric, Ralph S.']",mBio,,,True
078abb148599f16b6a3f8cfcf2599994dd9155f7,PMC,"Network Analysis of MERS Coronavirus within Households, Communities, and Hospitals to Identify Most Centralized and Super-Spreading in the Arabian Peninsula, 2012 to 2016",http://dx.doi.org/10.1155/2018/6725284,PMC5964435,29854034,CC BY,"Contact history is crucial during an infectious disease outbreak and vital when seeking to understand and predict the spread of infectious diseases in human populations. The transmission connectivity networks of people infected with highly contagious Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia were assessed to identify super-spreading events among the infected patients between 2012 and 2016. Of the 1379 MERS cases recorded during the study period, 321 (23.3%) cases were linked to hospital infection, out of which 203 (14.7%) cases occurred among healthcare workers. There were 1113 isolated cases while the number of recorded contacts per MERS patient is between 1 (n=210) and 17 (n=1), with a mean of 0.27 (SD = 0.76). Five super-important nodes were identified based on their high number of connected contacts worthy of prioritization (at least degree of 5). The number of secondary cases in each SSE varies (range, 5–17). The eigenvector centrality was significantly (p < 0.05) associated with place of exposure, with hospitals having on average significantly higher eigenvector centrality than other places of exposure. Results suggested that being a healthcare worker has a higher eigenvector centrality score on average than being nonhealthcare workers. Pathogenic droplets are easily transmitted within a confined area of hospitals; therefore, control measures should be put in place to curtail the number of hospital visitors and movements of nonessential staff within the healthcare facility with MERS cases.",2018 May 7,"['Adegboye, Oyelola A.', 'Elfaki, Faiz']",Can J Infect Dis Med Microbiol,,,True
60c8949b06f825932f883b28f0be1251cefd2525,PMC,Lectins as Promising Therapeutics for the Prevention and Treatment of HIV and Other Potential Coinfections,http://dx.doi.org/10.1155/2018/3750646,PMC5964492,29854749,CC BY,"Human immunodeficiency virus-acquired immunodeficiency syndrome (HIV/AIDS) remains a global health problem. Current therapeutics specifically target the viral pathogen at various stages of its life cycle, although complex interactions between HIV and other pathogenic organisms are evident. Targeting HIV and concomitant infectious pathogens simultaneously, both by therapeutic regimens and in prevention strategies, would help contain the AIDS pandemic. Lectins, a ubiquitous group of proteins that specifically bind glycosylated molecules, are interesting compounds that could be used for this purpose, with demonstrated anti-HIV properties. In addition, potential coinfecting pathogens, including other enveloped viruses, bacteria, yeasts and fungi, and protozoa, display sugar-coated macromolecules on their surfaces, making them potential targets of lectins. This review summarizes the currently available findings suggesting that lectins should be further developed to simultaneously fight the AIDS pandemic and concomitant infections in HIV infected individuals.",2018 May 8,"['Mazalovska, Milena', 'Kouokam, J. Calvin']",Biomed Res Int,,,True
798026310eaadd09df393473a730d6935f91b4d4,PMC,Comprehensive Analysis and Comparison on the Codon Usage Pattern of Whole Mycobacterium tuberculosis Coding Genome from Different Area,http://dx.doi.org/10.1155/2018/3574976,PMC5964552,29854746,CC BY,"Phenomenon of unequal use of synonymous codons in Mycobacterium tuberculosis is common. Codon usage bias not only plays an important regulatory role at the level of gene expression, but also helps in improving the accuracy and efficiency of translation. Meanwhile, codon usage pattern of Mycobacterium tuberculosis genome is important for interpreting evolutionary characteristics in species. In order to investigate the codon usage pattern of the Mycobacterium tuberculosis genome, 12 Mycobacterium tuberculosis genomes from different area are downloaded from the GeneBank. The correlations between G(3), GC(12), whole GC content, codon adaptation index, codon bias index, and so on of Mycobacterium tuberculosis genomes are calculated. The ENC-plot, relationship between A(3)/(A(3) + T(3)) and G(3)/(G(3) + C(3)), GC(12) versus GC(3) plot, and the RSCU of overall/separated genomes all show that the codon usage bias exists in all 12 Mycobacterium tuberculosis genomes. Lastly, relationship between CBI and the equalization of ENC shows a strong negative correlation between them. The relationship between protein length and GC content (GC(3) and GC(12)) shows that more obvious differences in the GC content may be in shorter protein. These results show that codon usage bias existing in the Mycobacterium tuberculosis genomes could be used for further study on their evolutionary phenomenon.",2018 May 8,"['Gun, Li', 'Yumiao, Ren', 'Haixian, Pan', 'Liang, Zhang']",Biomed Res Int,,,True
6e1e3f91f3642424e7328ee1fafc4151b7ba826c,PMC,"Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis",http://dx.doi.org/10.1186/s12890-018-0638-0,PMC5964678,29788932,CC BY,"Bronchiectasis is a disease associated with chronic progressive and irreversible dilatation of the bronchi and is characterised by chronic infection and associated inflammation. The prevalence of bronchiectasis is age-related and there is some geographical variation in incidence, prevalence and clinical features. Most bronchiectasis is reported to be idiopathic however post-infectious aetiologies dominate across Asia especially secondary to tuberculosis. Most focus to date has been on the study of airway bacteria, both as colonisers and causes of exacerbations. Modern molecular technologies including next generation sequencing (NGS) have become invaluable tools to identify microorganisms directly from sputum and which are difficult to culture using traditional agar based methods. These have provided important insight into our understanding of emerging pathogens in the airways of people with bronchiectasis and the geographical differences that occur. The contribution of the lung microbiome, its ethnic variation, and subsequent roles in disease progression and response to therapy across geographic regions warrant further investigation. This review summarises the known geographical differences in the aetiology, epidemiology and microbiology of bronchiectasis. Further, we highlight the opportunities offered by emerging molecular technologies such as -omics to further dissect out important ethnic differences in the prognosis and management of bronchiectasis.",2018 May 22,"['Chandrasekaran, Ravishankar', 'Mac Aogáin, Micheál', 'Chalmers, James D.', 'Elborn, Stuart J.', 'Chotirmall, Sanjay H.']",BMC Pulm Med,,,True
16844dca24405d3c94a4366cd94598a6a7357fc8,PMC,"Pathogenesis, imaging and clinical characteristics of CF and non-CF bronchiectasis",http://dx.doi.org/10.1186/s12890-018-0630-8,PMC5964733,29788954,CC BY,"Bronchiectasis is a common feature of severe inherited and acquired pulmonary disease conditions. Among inherited diseases, cystic fibrosis (CF) is the major disorder associated with bronchiectasis, while acquired conditions frequently featuring bronchiectasis include post-infective bronchiectasis and chronic obstructive pulmonary disease (COPD). Mechanistically, bronchiectasis is driven by a complex interplay of inflammation and infection with neutrophilic inflammation playing a predominant role. The clinical characterization and management of bronchiectasis should involve a precise diagnostic workup, tailored therapeutic strategies and pulmonary imaging that has become an essential tool for the diagnosis and follow-up of bronchiectasis. Prospective future studies are required to optimize the diagnostic and therapeutic management of bronchiectasis, particularly in heterogeneous non-CF bronchiectasis populations.",2018 May 22,"['Schäfer, Jürgen', 'Griese, Matthias', 'Chandrasekaran, Ravishankar', 'Chotirmall, Sanjay H.', 'Hartl, Dominik']",BMC Pulm Med,,,True
e0a44f822e93cacdd3a42102e77f6adfc0519c1a,PMC,Viral pathogen discovery,http://dx.doi.org/10.1016/j.mib.2013.05.001,PMC5964995,23725672,CC BY,"Viral pathogen discovery is of critical importance to clinical microbiology, infectious diseases, and public health. Genomic approaches for pathogen discovery, including consensus polymerase chain reaction (PCR), microarrays, and unbiased next-generation sequencing (NGS), have the capacity to comprehensively identify novel microbes present in clinical samples. Although numerous challenges remain to be addressed, including the bioinformatics analysis and interpretation of large datasets, these technologies have been successful in rapidly identifying emerging outbreak threats, screening vaccines and other biological products for microbial contamination, and discovering novel viruses associated with both acute and chronic illnesses. Downstream studies such as genome assembly, epidemiologic screening, and a culture system or animal model of infection are necessary to establish an association of a candidate pathogen with disease.",2013 Aug 29,"Chiu, Charles Y",Curr Opin Microbiol,,,True
1f60f032bad1fcfb8d48b20527c347ec774d255e,PMC,No Room for Error: Empiric Treatment for Fulminant Pneumonia,http://dx.doi.org/10.5811/cpcem.2017.1.33213,PMC5965415,29849375,CC BY,"Early antibiotic administration is critical in cases of sepsis and severe community-acquired pneumonia, which is frequently due to Streptococcus pneumoniae, Staphylococcus aureus, Legionella species, or influenza. We describe the case of a 29-year-old previously healthy man who presented to an urban emergency department (ED) in the North Central U.S. with fever, hip pain, severe hypoxemia, and diffuse pulmonary infiltrates. He was intubated and received piperacillin/tazobactam, levofloxacin, vancomycin, and oseltamivir; given his fulminant presentation and predicted high mortality, doxycycline, methylprednisolone, and amphotericin B were also administered empirically in the ED. A respiratory culture eventually grew Blastomyces dermatitidis, and the patient survived. Severe acute respiratory distress syndrome due to fulminant pneumonitis carries a high mortality. Faced with this scenario and no room for error, it is important that the emergency physician cover for all possible pathogens, including zoonotic bacteria and endemic fungi.",2017 Mar 13,"['Prekker, Matthew E.', 'Smith, Stephen W.']",Clin Pract Cases Emerg Med,,,True
dc522664a7fd404e4e58448210812247a002e06f,PMC,Involvement of the renin-angiotensin system in the progression of severe hand-foot-and-mouth disease,http://dx.doi.org/10.1371/journal.pone.0197861,PMC5965884,29791486,CC BY,"BACKGROUND: Hand-foot-and-mouth disease (HFMD) is generally considered as a mild exanthematous disease to infants and young children worldwide. HFMD cases are usually mild and self-limiting but for few cases leads to complicated severe clinical outcomes, and even death. Previous studies have indicated that serum Ang II levels in patients with H7N9 infection were related to the severity of infection. However, the mechanisms underlying the pathogenesis of severe HFMD remain unclear. This study was undertaken to clarify the role of the renin-angiotensin system (RAS) in the progression of severe HFMD. METHODS: In the present study, 162 children including HFMD patients and healthy controls were recruited. The data was analyzed by time-series fashion. Concentrations of angiotensin II (Ang II) and noradrenaline (NA) in serum of patients were measured with ELISA. We established a mouse model for enterovirus 71 (EV71) infection and determined concentrations of Ang II, NA in tissue lysates at 3, 5 and 7 days post infection (dpi). RESULTS: The concentrations of Ang II and NA in serum of the HFMD patients with mild or severe symptoms were significantly higher than that in healthy controls. Additionally, the concentrations of Ang II and NA in serum of severe cases were significantly higher than those mild cases and the increased concentrations of Ang II and NA showed the same time trend during the progression of HFMD in the severe cases. Furthermore, the concentrations of Ang II and NA in target organs of EV71-infected mice including brains, skeletal muscle, and lungs were increased with the progression of EV71 infection in mice. Histopathological alterations were observed in the brains, skeletal muscle and lungs of EV71-infected mice. CONCLUSION: Our study suggested that activation of the RAS is implicated in the pathogenesis of severe HFMD.",2018 May 23,"['Zhang, Chao', 'Chen, Shuaiyin', 'Zhou, Guangyuan', 'Jin, Yuefei', 'Zhang, Rongguang', 'Yang, Haiyan', 'Xi, Yuanlin', 'Ren, Jingchao', 'Duan, Guangcai']",PLoS One,,,True
56964b8cbc98f8dd9a1a45190f0daceb59c62df9,PMC,Chaperna-Mediated Assembly of Ferritin-Based Middle East Respiratory Syndrome-Coronavirus Nanoparticles,http://dx.doi.org/10.3389/fimmu.2018.01093,PMC5966535,29868035,CC BY,"The folding of monomeric antigens and their subsequent assembly into higher ordered structures are crucial for robust and effective production of nanoparticle (NP) vaccines in a timely and reproducible manner. Despite significant advances in in silico design and structure-based assembly, most engineered NPs are refractory to soluble expression and fail to assemble as designed, presenting major challenges in the manufacturing process. The failure is due to a lack of understanding of the kinetic pathways and enabling technical platforms to ensure successful folding of the monomer antigens into regular assemblages. Capitalizing on a novel function of RNA as a molecular chaperone (chaperna: chaperone + RNA), we provide a robust protein-folding vehicle that may be implemented to NP assembly in bacterial hosts. The receptor-binding domain (RBD) of Middle East respiratory syndrome-coronavirus (MERS-CoV) was fused with the RNA-interaction domain (RID) and bacterioferritin, and expressed in Escherichia coli in a soluble form. Site-specific proteolytic removal of the RID prompted the assemblage of monomers into NPs, which was confirmed by electron microscopy and dynamic light scattering. The mutations that affected the RNA binding to RBD significantly increased the soluble aggregation into amorphous structures, reducing the overall yield of NPs of a defined size. This underscored the RNA-antigen interactions during NP assembly. The sera after mouse immunization effectively interfered with the binding of MERS-CoV RBD to the cellular receptor hDPP4. The results suggest that RNA-binding controls the overall kinetic network of the antigen folding pathway in favor of enhanced assemblage of NPs into highly regular and immunologically relevant conformations. The concentration of the ion Fe(2+), salt, and fusion linker also contributed to the assembly in vitro, and the stability of the NPs. The kinetic “pace-keeping” role of chaperna in the super molecular assembly of antigen monomers holds promise for the development and delivery of NPs and virus-like particles as recombinant vaccines and for serological detection of viral infections.",2018 May 17,"['Kim, Young-Seok', 'Son, Ahyun', 'Kim, Jihoon', 'Kwon, Soon Bin', 'Kim, Myung Hee', 'Kim, Paul', 'Kim, Jieun', 'Byun, Young Ho', 'Sung, Jemin', 'Lee, Jinhee', 'Yu, Ji Eun', 'Park, Chan', 'Kim, Yeon-Sook', 'Cho, Nam-Hyuk', 'Chang, Jun', 'Seong, Baik L.']",Front Immunol,,,True
3e86a490327b0f473d776363d3f2e67ddd04d681,PMC,Human Kinase/Phosphatase-Wide RNAi Screening Identified Checkpoint Kinase 2 as a Cellular Factor Facilitating Japanese Encephalitis Virus Infection,http://dx.doi.org/10.3389/fcimb.2018.00142,PMC5966567,29868498,CC BY,"Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, causes acute encephalitis in humans with high mortality. Not much is known about the interactions between viral and cellular factors that regulate JEV infection. By using a kinase/phosphatase-wide RNAi screening approach, we identified a cell cycle-regulating molecule, checkpoint kinase 2 (CHK2), that plays a role in regulating JEV replication. JEV infection induced G1 arrest and activated CHK2. Inactivation of CHK2 and its upstream ataxia-telangiectasia mutated kinase in JEV-infected cells by using inhibitors reduced virus replication. Likewise, JEV replication was significantly decreased by knockdown of CHK2 expression with shRNA-producing lentiviral transduction. We identified CHK2 as a cellular factor participating in JEV replication, for a new strategy in addressing JEV infection.",2018 May 17,"['Chan, Yi-Lin', 'Liao, Ching-Len', 'Lin, Yi-Ling']",Front Cell Infect Microbiol,,,True
4099867282145ec32ec26620f381a9251f160f3b,PMC,Predicting Interactions between Virus and Host Proteins Using Repeat Patterns and Composition of Amino Acids,http://dx.doi.org/10.1155/2018/1391265,PMC5966669,29854357,CC BY,"Previous methods for predicting protein-protein interactions (PPIs) were mainly focused on PPIs within a single species, but PPIs across different species have recently emerged as an important issue in some areas such as viral infection. The primary focus of this study is to predict PPIs between virus and its targeted host, which are involved in viral infection. We developed a general method that predicts interactions between virus and host proteins using the repeat patterns and composition of amino acids. In independent testing of the method with PPIs of new viruses and hosts, it showed a high performance comparable to the best performance of other methods for single virus-host PPIs. In comparison of our method with others using same datasets, our method outperformed the others. The repeat patterns and composition of amino acids are simple, yet powerful features for predicting virus-host PPIs. The method developed in this study will help in finding new virus-host PPIs for which little information is available.",2018 May 9,"['Alguwaizani, Saud', 'Park, Byungkyu', 'Zhou, Xiang', 'Huang, De-Shuang', 'Han, Kyungsook']",J Healthc Eng,,,True
27ae0e9aa55fc12f0795960f493cc0ac3801a20f,PMC,The role of human Metapneumovirus genetic diversity and nasopharyngeal viral load on symptom severity in adults,http://dx.doi.org/10.1186/s12985-018-1005-8,PMC5966857,29792212,CC BY,"BACKGROUND: Human metapneumovirus (HMPV) is established as one of the causative agents of respiratory tract infections. To date, there are limited reports that describe the effect of HMPV genotypes and/or viral load on disease pathogenesis in adults. This study aims to determine the role of HMPV genetic diversity and nasopharyngeal viral load on symptom severity in outpatient adults with acute respiratory tract infections. METHODS: Severity of common cold symptoms of patients from a teaching hospital was assessed by a four-category scale and summed to obtain the total symptom severity score (TSSS). Association between the fusion and glycoprotein genes diversity, viral load (quantified using an improved RT-qPCR assay), and symptom severity were analyzed using bivariate and linear regression analyses. RESULTS: Among 81/3706 HMPV-positive patients, there were no significant differences in terms of demographics, number of days elapsed between symptom onset and clinic visit, respiratory symptoms manifestation and severity between different HMPV genotypes/sub-lineages. Surprisingly, elderly patients (≥65 years old) had lower severity of symptoms (indicated by TSSS) than young and middle age adults (p = 0.008). Nasopharyngeal viral load did not correlate with nor predict symptom severity of HMPV infection. Interestingly, at 3–5 days after symptom onset, genotype A-infected patients had higher viral load compared to genotype B (4.4 vs. 3.3 log(10) RNA copies/μl) (p = 0.003). CONCLUSIONS: Overall, HMPV genetic diversity and viral load did not impact symptom severity in adults with acute respiratory tract infections. Differences in viral load dynamics over time between genotypes may have important implications on viral transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1005-8) contains supplementary material, which is available to authorized users.",2018 May 23,"['Oong, Xiang Yong', 'Chook, Jack Bee', 'Ng, Kim Tien', 'Chow, Wei Zhen', 'Chan, Kok Gan', 'Hanafi, Nik Sherina', 'Pang, Yong Kek', 'Chan, Yoke Fun', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
6283f1857cb5e2a448314edd73d5ff5d2203c566,PMC,The role of human Metapneumovirus genetic diversity and nasopharyngeal viral load on symptom severity in adults,http://dx.doi.org/10.1186/s12985-018-1005-8,PMC5966857,29792212,CC BY,"BACKGROUND: Human metapneumovirus (HMPV) is established as one of the causative agents of respiratory tract infections. To date, there are limited reports that describe the effect of HMPV genotypes and/or viral load on disease pathogenesis in adults. This study aims to determine the role of HMPV genetic diversity and nasopharyngeal viral load on symptom severity in outpatient adults with acute respiratory tract infections. METHODS: Severity of common cold symptoms of patients from a teaching hospital was assessed by a four-category scale and summed to obtain the total symptom severity score (TSSS). Association between the fusion and glycoprotein genes diversity, viral load (quantified using an improved RT-qPCR assay), and symptom severity were analyzed using bivariate and linear regression analyses. RESULTS: Among 81/3706 HMPV-positive patients, there were no significant differences in terms of demographics, number of days elapsed between symptom onset and clinic visit, respiratory symptoms manifestation and severity between different HMPV genotypes/sub-lineages. Surprisingly, elderly patients (≥65 years old) had lower severity of symptoms (indicated by TSSS) than young and middle age adults (p = 0.008). Nasopharyngeal viral load did not correlate with nor predict symptom severity of HMPV infection. Interestingly, at 3–5 days after symptom onset, genotype A-infected patients had higher viral load compared to genotype B (4.4 vs. 3.3 log(10) RNA copies/μl) (p = 0.003). CONCLUSIONS: Overall, HMPV genetic diversity and viral load did not impact symptom severity in adults with acute respiratory tract infections. Differences in viral load dynamics over time between genotypes may have important implications on viral transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1005-8) contains supplementary material, which is available to authorized users.",2018 May 23,"['Oong, Xiang Yong', 'Chook, Jack Bee', 'Ng, Kim Tien', 'Chow, Wei Zhen', 'Chan, Kok Gan', 'Hanafi, Nik Sherina', 'Pang, Yong Kek', 'Chan, Yoke Fun', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,True
50590ed5c45f88f394b47393781877fa967440f2,PMC,The role of human Metapneumovirus genetic diversity and nasopharyngeal viral load on symptom severity in adults,http://dx.doi.org/10.1186/s12985-018-1005-8,PMC5966857,29792212,CC BY,"BACKGROUND: Human metapneumovirus (HMPV) is established as one of the causative agents of respiratory tract infections. To date, there are limited reports that describe the effect of HMPV genotypes and/or viral load on disease pathogenesis in adults. This study aims to determine the role of HMPV genetic diversity and nasopharyngeal viral load on symptom severity in outpatient adults with acute respiratory tract infections. METHODS: Severity of common cold symptoms of patients from a teaching hospital was assessed by a four-category scale and summed to obtain the total symptom severity score (TSSS). Association between the fusion and glycoprotein genes diversity, viral load (quantified using an improved RT-qPCR assay), and symptom severity were analyzed using bivariate and linear regression analyses. RESULTS: Among 81/3706 HMPV-positive patients, there were no significant differences in terms of demographics, number of days elapsed between symptom onset and clinic visit, respiratory symptoms manifestation and severity between different HMPV genotypes/sub-lineages. Surprisingly, elderly patients (≥65 years old) had lower severity of symptoms (indicated by TSSS) than young and middle age adults (p = 0.008). Nasopharyngeal viral load did not correlate with nor predict symptom severity of HMPV infection. Interestingly, at 3–5 days after symptom onset, genotype A-infected patients had higher viral load compared to genotype B (4.4 vs. 3.3 log(10) RNA copies/μl) (p = 0.003). CONCLUSIONS: Overall, HMPV genetic diversity and viral load did not impact symptom severity in adults with acute respiratory tract infections. Differences in viral load dynamics over time between genotypes may have important implications on viral transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1005-8) contains supplementary material, which is available to authorized users.",2018 May 23,"['Oong, Xiang Yong', 'Chook, Jack Bee', 'Ng, Kim Tien', 'Chow, Wei Zhen', 'Chan, Kok Gan', 'Hanafi, Nik Sherina', 'Pang, Yong Kek', 'Chan, Yoke Fun', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
cd96e05dab18e829e65e3b72578c353843bc5421,PMC,The role of human Metapneumovirus genetic diversity and nasopharyngeal viral load on symptom severity in adults,http://dx.doi.org/10.1186/s12985-018-1005-8,PMC5966857,29792212,CC BY,"BACKGROUND: Human metapneumovirus (HMPV) is established as one of the causative agents of respiratory tract infections. To date, there are limited reports that describe the effect of HMPV genotypes and/or viral load on disease pathogenesis in adults. This study aims to determine the role of HMPV genetic diversity and nasopharyngeal viral load on symptom severity in outpatient adults with acute respiratory tract infections. METHODS: Severity of common cold symptoms of patients from a teaching hospital was assessed by a four-category scale and summed to obtain the total symptom severity score (TSSS). Association between the fusion and glycoprotein genes diversity, viral load (quantified using an improved RT-qPCR assay), and symptom severity were analyzed using bivariate and linear regression analyses. RESULTS: Among 81/3706 HMPV-positive patients, there were no significant differences in terms of demographics, number of days elapsed between symptom onset and clinic visit, respiratory symptoms manifestation and severity between different HMPV genotypes/sub-lineages. Surprisingly, elderly patients (≥65 years old) had lower severity of symptoms (indicated by TSSS) than young and middle age adults (p = 0.008). Nasopharyngeal viral load did not correlate with nor predict symptom severity of HMPV infection. Interestingly, at 3–5 days after symptom onset, genotype A-infected patients had higher viral load compared to genotype B (4.4 vs. 3.3 log(10) RNA copies/μl) (p = 0.003). CONCLUSIONS: Overall, HMPV genetic diversity and viral load did not impact symptom severity in adults with acute respiratory tract infections. Differences in viral load dynamics over time between genotypes may have important implications on viral transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1005-8) contains supplementary material, which is available to authorized users.",2018 May 23,"['Oong, Xiang Yong', 'Chook, Jack Bee', 'Ng, Kim Tien', 'Chow, Wei Zhen', 'Chan, Kok Gan', 'Hanafi, Nik Sherina', 'Pang, Yong Kek', 'Chan, Yoke Fun', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
ce5c4fe6e5dd377573789ca16da5c3fe6f47b74d,PMC,The role of human Metapneumovirus genetic diversity and nasopharyngeal viral load on symptom severity in adults,http://dx.doi.org/10.1186/s12985-018-1005-8,PMC5966857,29792212,CC BY,"BACKGROUND: Human metapneumovirus (HMPV) is established as one of the causative agents of respiratory tract infections. To date, there are limited reports that describe the effect of HMPV genotypes and/or viral load on disease pathogenesis in adults. This study aims to determine the role of HMPV genetic diversity and nasopharyngeal viral load on symptom severity in outpatient adults with acute respiratory tract infections. METHODS: Severity of common cold symptoms of patients from a teaching hospital was assessed by a four-category scale and summed to obtain the total symptom severity score (TSSS). Association between the fusion and glycoprotein genes diversity, viral load (quantified using an improved RT-qPCR assay), and symptom severity were analyzed using bivariate and linear regression analyses. RESULTS: Among 81/3706 HMPV-positive patients, there were no significant differences in terms of demographics, number of days elapsed between symptom onset and clinic visit, respiratory symptoms manifestation and severity between different HMPV genotypes/sub-lineages. Surprisingly, elderly patients (≥65 years old) had lower severity of symptoms (indicated by TSSS) than young and middle age adults (p = 0.008). Nasopharyngeal viral load did not correlate with nor predict symptom severity of HMPV infection. Interestingly, at 3–5 days after symptom onset, genotype A-infected patients had higher viral load compared to genotype B (4.4 vs. 3.3 log(10) RNA copies/μl) (p = 0.003). CONCLUSIONS: Overall, HMPV genetic diversity and viral load did not impact symptom severity in adults with acute respiratory tract infections. Differences in viral load dynamics over time between genotypes may have important implications on viral transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1005-8) contains supplementary material, which is available to authorized users.",2018 May 23,"['Oong, Xiang Yong', 'Chook, Jack Bee', 'Ng, Kim Tien', 'Chow, Wei Zhen', 'Chan, Kok Gan', 'Hanafi, Nik Sherina', 'Pang, Yong Kek', 'Chan, Yoke Fun', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
59cbbd255acc779e36311d1c4f5be34bdc904888,PMC,The role of human Metapneumovirus genetic diversity and nasopharyngeal viral load on symptom severity in adults,http://dx.doi.org/10.1186/s12985-018-1005-8,PMC5966857,29792212,CC BY,"BACKGROUND: Human metapneumovirus (HMPV) is established as one of the causative agents of respiratory tract infections. To date, there are limited reports that describe the effect of HMPV genotypes and/or viral load on disease pathogenesis in adults. This study aims to determine the role of HMPV genetic diversity and nasopharyngeal viral load on symptom severity in outpatient adults with acute respiratory tract infections. METHODS: Severity of common cold symptoms of patients from a teaching hospital was assessed by a four-category scale and summed to obtain the total symptom severity score (TSSS). Association between the fusion and glycoprotein genes diversity, viral load (quantified using an improved RT-qPCR assay), and symptom severity were analyzed using bivariate and linear regression analyses. RESULTS: Among 81/3706 HMPV-positive patients, there were no significant differences in terms of demographics, number of days elapsed between symptom onset and clinic visit, respiratory symptoms manifestation and severity between different HMPV genotypes/sub-lineages. Surprisingly, elderly patients (≥65 years old) had lower severity of symptoms (indicated by TSSS) than young and middle age adults (p = 0.008). Nasopharyngeal viral load did not correlate with nor predict symptom severity of HMPV infection. Interestingly, at 3–5 days after symptom onset, genotype A-infected patients had higher viral load compared to genotype B (4.4 vs. 3.3 log(10) RNA copies/μl) (p = 0.003). CONCLUSIONS: Overall, HMPV genetic diversity and viral load did not impact symptom severity in adults with acute respiratory tract infections. Differences in viral load dynamics over time between genotypes may have important implications on viral transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1005-8) contains supplementary material, which is available to authorized users.",2018 May 23,"['Oong, Xiang Yong', 'Chook, Jack Bee', 'Ng, Kim Tien', 'Chow, Wei Zhen', 'Chan, Kok Gan', 'Hanafi, Nik Sherina', 'Pang, Yong Kek', 'Chan, Yoke Fun', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,True
024d0bef5417a110fb52607e85ec80eb4d7d92a3,PMC,Nucleocapsid protein-dependent assembly of the RNA packaging signal of Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1186/s12929-018-0449-x,PMC5966903,29793506,CC BY,"BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) consists of a positive-sense, single-stranded RNA genome and four structural proteins: the spike, envelope, membrane, and nucleocapsid protein. The assembly of the viral genome into virus particles involves viral structural proteins and is believed to be mediated through recognition of specific sequences and RNA structures of the viral genome. METHODS AND RESULTS: A culture system for the production of MERS coronavirus-like particles (MERS VLPs) was determined and established by electron microscopy and the detection of coexpressed viral structural proteins. Using the VLP system, a 258-nucleotide RNA fragment, which spans nucleotides 19,712 to 19,969 of the MERS-CoV genome (designated PS258(19712–19969)(ME)), was identified to function as a packaging signal. Assembly of the RNA packaging signal into MERS VLPs is dependent on the viral nucleocapsid protein. In addition, a 45-nucleotide stable stem-loop substructure of the PS258(19712–19969)(ME) interacted with both the N-terminal domain and the C-terminal domain of the viral nucleocapsid protein. Furthermore, a functional SARS-CoV RNA packaging signal failed to assemble into the MERS VLPs, which indicated virus-specific assembly of the RNA genome. CONCLUSIONS: A MERS-oV RNA packaging signal was identified by the detection of GFP expression following an incubation of MERS VLPs carrying the heterologous mRNA GFP-PS258(19712–19969)(ME) with virus permissive Huh7 cells. The MERS VLP system could help us in understanding virus infection and morphogenesis.",2018 May 24,"['Hsin, Wei-Chen', 'Chang, Chan-Hua', 'Chang, Chi-You', 'Peng, Wei-Hao', 'Chien, Chung-Liang', 'Chang, Ming-Fu', 'Chang, Shin C.']",J Biomed Sci,,,True
420944cb316179f6529d1d7a99d92910df8e49a5,PMC,Plant Viral Proteases: Beyond the Role of Peptide Cutters,http://dx.doi.org/10.3389/fpls.2018.00666,PMC5967125,29868107,CC BY,"Almost half of known plant viral species rely on proteolytic cleavages as key co- and post-translational modifications throughout their infection cycle. Most of these viruses encode their own endopeptidases, proteases with high substrate specificity that internally cleave large polyprotein precursors for the release of functional sub-units. Processing of the polyprotein, however, is not an all-or-nothing process in which endopeptidases act as simple peptide cutters. On the contrary, spatial-temporal modulation of these polyprotein cleavage events is crucial for a successful viral infection. In this way, the processing of the polyprotein coordinates viral replication, assembly and movement, and has significant impact on pathogen fitness and virulence. In this mini-review, we give an overview of plant viral proteases emphasizing their importance during viral infections and the varied functionalities that result from their proteolytic activities.",2018 May 17,"['Rodamilans, Bernardo', 'Shan, Hongying', 'Pasin, Fabio', 'García, Juan Antonio']",Front Plant Sci,,,True
cd22fe835feb95cc3cc02e08dd38f962d4f69185,PMC,"Revalidation and genetic characterization of new members of Group C (Orthobunyavirus genus, Peribunyaviridae family) isolated in the Americas",http://dx.doi.org/10.1371/journal.pone.0197294,PMC5967719,29795585,CC BY,"Group C serogroup includes members of the Orthobunyavirus genus (family Peribunyaviridae) and comprises 15 arboviruses that can be associated with febrile illness in humans. Although previous studies described the genome characterization of Group C orthobunyavirus, there is a gap in genomic information about the other viruses in this group. Therefore, in this study, complete genomes of members of Group C serogroup were sequenced or re-sequenced and used for genetic characterization, as well as to understand their phylogenetic and evolutionary aspects. Thus, our study reported the genomes of three new members in Group C virus (Apeu strain BeAn848, Itaqui strain BeAn12797 and Nepuyo strain BeAn10709), as well as re-sequencing of original strains of five members: Caraparu (strain BeAn3994), Madrid (strain BT4075), Murucutu (strain BeAn974), Oriboca (strain BeAn17), and Marituba (strain BeAn15). These viruses presented a typical genomic organization related to members of the Orthobunyavirus genus. Interestingly, all viruses of this serogroup showed an open reading frame (ORF) that encodes the putative nonstructural NSs protein that precedes the nucleoprotein ORF, an unprecedented fact in Group C virus. Also, we confirmed the presence of natural reassortment events. This study expands the genomic information of Group C viruses, as well as revalidates the genomic organization of viruses that were previously reported.",2018 May 24,"['Nunes, Márcio Roberto Teixeira', 'de Souza, William Marciel', 'Acrani, Gustavo Olszanski', 'Cardoso, Jedson Ferreira', 'da Silva, Sandro Patroca', 'Badra, Soraya Jabur', 'Figueiredo, Luiz Tadeu Moraes', 'Vasconcelos, Pedro Fernando da Costa']",PLoS One,,,True
c8a09ce3cbd5d88ceb3bb530003b2f4a46d92d3f,PMC,Virus survey in populations of two subspecies of bent-winged bats (Miniopterus orianae bassanii and oceanensis) in south-eastern Australia reveals a high prevalence of diverse herpesviruses,http://dx.doi.org/10.1371/journal.pone.0197625,PMC5967723,29795610,CC BY,"While bats are often viewed as carriers of infectious disease agents, little research has been conducted on the effects these potential pathogens may have on the bat populations themselves. The southern bent-winged bat (Miniopterus orianae bassanii) is a critically endangered subspecies endemic to south-eastern Australia. Population numbers of this bat have been declining for the past 50 years, but the reasons for this are unclear. As part of a larger study to determine if disease could be a contributing factor to this decline, 351 southern bent-winged bats from four locations were captured, and oral swabs were collected and tested for the presence of potentially pathogenic viruses. Results were compared with those obtained from 116 eastern bent-winged bats (Miniopterus orianae oceanensis) from three different locations. The eastern bent-winged bat is a related but more common and widespread subspecies whose geographical range overlaps partly with southern bent-winged bats. Herpesviruses were detected in bent-winged bats from all seven locations. At least six novel herpesviruses (five betaherpesviruses and one gammaherpesvirus) were identified. The prevalence of herpesvirus infection was higher in eastern bent-winged bats (44%, 51/116), compared to southern bent-winged bats (27%, 95/351), although this varied across the locations and sampling periods. Adenoviruses and a range of different RNA viruses (lyssaviruses, filoviruses, coronaviruses and henipaviruses) were also tested for but not detected. The detected herpesviruses did not appear to be associated with obvious ill health, and may thus not be playing a role in the population decline of the southern bent-winged bat. The detection of multiple novel herpesviruses at a high prevalence of infection is consistent with our understanding of bats as hosts to a rich diversity of viruses.",2018 May 24,"['Holz, Peter H.', 'Lumsden, Linda F.', 'Druce, Julian', 'Legione, Alistair R.', 'Vaz, Paola', 'Devlin, Joanne M.', 'Hufschmid, Jasmin']",PLoS One,,,True
aa2ed61346b7c005b96d661476a671b555b2a93a,PMC,Asymptomatic Middle East Respiratory Syndrome coronavirus infection using a serologic survey in Korea,http://dx.doi.org/10.4178/epih.e2018014,PMC5968208,29656631,CC BY,"OBJECTIVES: The rates of asymptomatic infection with Middle East Respiratory Syndrome (MERS) coronavirus vary. A serologic study was conducted to determine the asymptomatic MERS infection rate in healthcare workers and non-healthcare workers by exposure status. METHODS: Study participants were selected from contacts of MERS patients based on a priority system in 4 regions strongly affected by the 2015 MERS outbreak. A sero-epidemiological survey was performed in 1,610 contacts (average duration from exposure to test, 4.8 months), and the collected sera were tested using an enzyme-linked immunespecific assay (ELISA), immunofluorescence assay (IFA), and plaque reduction neutralization antibody test (PRNT). Among the 1,610 contacts, there were 7 ELISA-positive cases, of which 1 exhibited positive IFA and PRNT results. RESULTS: The asymptomatic infection rate was 0.060% (95% confidence interval, 0.002 to 0.346). The asymptomatic MERS case was a patient who had been hospitalized with patient zero on the same floor of the hospital at the same time. The case was quarantined at home for 2 weeks after discharge, and had underlying diseases, including hypertension, angina, and degenerative arthritis. CONCLUSIONS: The asymptomatic infection was acquired via healthcare-associated transmission. Thus, it is necessary to extend serologic studies to include inpatient contacts who have no symptoms.",2018 Apr 15,"['Song, Yeong-jun', 'Yang, Jeong-Sun', 'Yoon, Hee Jung', 'Nam, Hae-Sung', 'Lee, Soon Young', 'Cheong, Hae-Kwan', 'Park, Woo-Jung', 'Park, Sung Han', 'Choi, Bo Youl', 'Kim, Sung Soon', 'Ki, Moran']",Epidemiol Health,,,True
f0ccdcc81b93aa3feaa5291c471f2fa25e1128b6,PMC,An effective strategy for recapitulating N-terminal heptad repeat trimers in enveloped virus surface glycoproteins for therapeutic applications,http://dx.doi.org/10.1039/c5sc04046a,PMC5968561,29899942,CC BY,"Sequestering peptides derived from the N-terminal heptad repeat (NHR) of class I viral fusion proteins into a non-aggregating trimeric coiled-coil conformation remains a major challenge. Here, we implemented a synthetic strategy to stabilize NHR-helical trimers, with the human immunodeficiency virus type 1 (HIV-1) gp41 fusion protein as the initial focus. A set of trimeric scaffolds was realized in a synthetic gp41 NHR-derived peptide sequence by relying on the tractability of coiled-coil structures and an additional isopeptide bridge-tethering strategy. Among them, (N36M)(3) folded as a highly stable helical trimer and exhibited promising inhibitory activity against HIV-1 infection, exceptional resistance to proteolysis, and effective native ligand-binding capability. We anticipate that the trimeric coiled-coil recapitulation methodology described herein may have broader applicability to yield NHR trimers of other class I enveloped viruses and to prepare helical tertiary structure mimetics of certain natural protein–protein interactions for biomedical applications.",2016 Mar 1,"['Lai, Wenqing', 'Wang, Chao', 'Yu, Fei', 'Lu, Lu', 'Wang, Qian', 'Jiang, Xifeng', 'Xu, Xiaoyu', 'Zhang, Tianhong', 'Wu, Shengming', 'Zheng, Xi', 'Zhang, Zhenqing', 'Dong, Fangting', 'Jiang, Shibo', 'Liu, Keliang']",Chem Sci,,,False
6057b3c4213bf3823366f1cd497b0a7e311b5461,PMC,An effective strategy for recapitulating N-terminal heptad repeat trimers in enveloped virus surface glycoproteins for therapeutic applications,http://dx.doi.org/10.1039/c5sc04046a,PMC5968561,29899942,CC BY,"Sequestering peptides derived from the N-terminal heptad repeat (NHR) of class I viral fusion proteins into a non-aggregating trimeric coiled-coil conformation remains a major challenge. Here, we implemented a synthetic strategy to stabilize NHR-helical trimers, with the human immunodeficiency virus type 1 (HIV-1) gp41 fusion protein as the initial focus. A set of trimeric scaffolds was realized in a synthetic gp41 NHR-derived peptide sequence by relying on the tractability of coiled-coil structures and an additional isopeptide bridge-tethering strategy. Among them, (N36M)(3) folded as a highly stable helical trimer and exhibited promising inhibitory activity against HIV-1 infection, exceptional resistance to proteolysis, and effective native ligand-binding capability. We anticipate that the trimeric coiled-coil recapitulation methodology described herein may have broader applicability to yield NHR trimers of other class I enveloped viruses and to prepare helical tertiary structure mimetics of certain natural protein–protein interactions for biomedical applications.",2016 Mar 1,"['Lai, Wenqing', 'Wang, Chao', 'Yu, Fei', 'Lu, Lu', 'Wang, Qian', 'Jiang, Xifeng', 'Xu, Xiaoyu', 'Zhang, Tianhong', 'Wu, Shengming', 'Zheng, Xi', 'Zhang, Zhenqing', 'Dong, Fangting', 'Jiang, Shibo', 'Liu, Keliang']",Chem Sci,,,False
d05ba19fb87837ac31ae8501669bb7f74fd5739f,PMC,Complete Genome Sequences of Four Novel Human Coronavirus OC43 Isolates Associated with Severe Acute Respiratory Infection,http://dx.doi.org/10.1128/genomeA.00452-18,PMC5968726,29798929,CC BY,"We report here the complete genome sequences of four human coronavirus (HCoV) OC43 isolates generated using targeted viral nucleic acid capture and next-generation sequencing; the isolates were collected in New Mexico and Arkansas, USA, in February (HCoV-OC43/USA/TCNP_0070/2016) and March (HCoV-OC43/USA/ACRI_0052/2016) 2016 and January 2017 (HCoV-OC43/USA/TCNP_00204/2017 and HCoV-OC43/USA/TCNP_00212/2017).",2018 May 24,"['Dinwiddie, Darrell L.', 'Hardin, Olga', 'Denson, Jesse L.', 'Kincaid, John C.', 'Schwalm, Kurt C.', 'Stoner, Ashley N.', 'Abramo, Thomas J.', 'Thompson, Tonya M.', 'Putt, Claire M.', 'Young, Stephen A.', 'Dehority, Walter N.', 'Kennedy, Joshua L.']",Genome Announc,,,True
9fdf9d656c7c79e8d8746fb3a5beeff11894dc8e,PMC,A road for a promising future for China’s primates: The potential for restoration,http://dx.doi.org/10.24272/j.issn.2095-8137.2018.032,PMC5968852,29551761,CC BY,"China is one of the most dynamic countries of the world and it shelters some amazing levels of biodiversity, including some very special primate species. However, primarily as a result of forest loss, most of which occurred in historical times, approximately 70% of China’s primate species have less than 3 000 individuals. Here I evaluate one road for future conservation/development that could produce very positive gains for China’s primates; namely forest restoration. I argue that for a large scale restoration project to be possible two conditions must be met; the right societal conditions must exist and the right knowledge must be in hand. This evaluation suggests that the restoration of native forest to support many of China’s primates holds great potential to advance conservation goals and to promote primate population recovery.",2018 Jul 18,"Chapman, Colin A.",Zool Res,,,True
58432d2ad49266df441de364700684534498b777,PMC,Metagenomic analysis of the RNA fraction of the fecal virome indicates high diversity in pigs infected by porcine endemic diarrhea virus in the United States,http://dx.doi.org/10.1186/s12985-018-1001-z,PMC5970503,29801460,CC BY,"BACKGROUND: Emergence and re-emergence of porcine epidemic diarrhea virus (PEDV) in North America, Asia and Europe has caused severe economic loss to the global swine industry. However, the virome of PEDV infected pigs and its effect on disease severity remains unknown. The advancements of sequencing technology have made it possible to characterize the entire microbiome of different body sites for any host. METHODS: The objective of this study was to characterize the RNA virome in PEDV-positive pigs using the hypothesis-free metagenomics approach based on next-generation sequencing. Specifically, 217 PEDV-positive swine fecal swab samples collected from diarrheic piglets over 17 US states during 2015–2016 were analyzed. RESULTS: A Kraken algorithm-based bioinformatics analysis revealed the presence of up to 9 different RNA genera besides PEDV (Alphacoronavirus genus), including Mamastrovirus (52%, 113/217), Enterovirus (39%, 85/217), Sapelovirus (31%, 67/217), Posavirus (30%, 66/217), Kobuvirus (23%, 49/217), Sapovirus (13%, 28/217), Teschovirus (10%, 22/217), Pasivirus (9%, 20/217), and Deltacoronavirus (3%, 6/217). There were 58 out of 217 piglets (27%) have PEDV infection alone whereas the remaining 159 (73%) shed 2 up to 9 different viruses. CONCLUSION: These findings demonstrated that PEDV infected diarrheic pigs had an extensive RNA viral flora consisting of four different families: Astroviridae, Picornaviridae, Caliciviridae, and Coronaviridae.",2018 May 25,"['Chen, Qi', 'Wang, Leyi', 'Zheng, Ying', 'Zhang, Jianqiang', 'Guo, Baoqing', 'Yoon, Kyoung-Jin', 'Gauger, Phillip C.', 'Harmon, Karen M.', 'Main, Rodger G.', 'Li, Ganwu']",Virol J,,,True
056b14876b632e0c4f3e75d79ac2d2f77b56fe61,PMC,An infectious way to teach students about outbreaks,http://dx.doi.org/10.1016/j.epidem.2017.12.002,PMC5971212,29289499,CC BY,"The study of infectious disease outbreaks is required to train today’s epidemiologists. A typical way to introduce and explain key epidemiological concepts is through the analysis of a historical outbreak. There are, however, few training options that explicitly utilise real-time simulated stochastic outbreaks where the participants themselves comprise the dataset they subsequently analyse. In this paper, we present a teaching exercise in which an infectious disease outbreak is simulated over a five-day period and subsequently analysed. We iteratively developed the teaching exercise to offer additional insight into analysing an outbreak. An R package for visualisation, analysis and simulation of the outbreak data was developed to accompany the practical to reinforce learning outcomes. Computer simulations of the outbreak revealed deviations from observed dynamics, highlighting how simplifying assumptions conventionally made in mathematical models often differ from reality. Here we provide a pedagogical tool for others to use and adapt in their own settings.",2018 Jun,"['Cremin, Íde', 'Watson, Oliver', 'Heffernan, Alastair', 'Imai, Natsuko', 'Ahmed, Norin', 'Bivegete, Sandra', 'Kimani, Teresia', 'Kyriacou, Demetris', 'Mahadevan, Preveina', 'Mustafa, Rima', 'Pagoni, Panagiota', 'Sophiea, Marisa', 'Whittaker, Charlie', 'Beacroft, Leo', 'Riley, Steven', 'Fisher, Matthew C.']",Epidemics,,,False
44001ef9803c7765b699fd7a95eb1edac878c840,PMC,Multicenter Evaluation of BioFire FilmArray Respiratory Panel 2 for Detection of Viruses and Bacteria in Nasopharyngeal Swab Samples,http://dx.doi.org/10.1128/JCM.01945-17,PMC5971546,29593057,CC BY,"The FilmArray Respiratory Panel 2 (RP2) is a multiplex in vitro diagnostic test for the simultaneous and rapid (∼45-min) detection of 22 pathogens directly from nasopharyngeal swab (NPS) samples. It contains updated (and in some instances redesigned) assays that improve upon the FilmArray Respiratory Panel (RP; version 1.7), with a faster run time. The organisms identified are adenovirus, coronavirus 229E, coronavirus HKU1, coronavirus NL63, coronavirus OC43, human metapneumovirus, human rhinovirus/enterovirus, influenza virus A, influenza virus A H1, influenza virus A H1-2009, influenza virus A H3, influenza virus B, parainfluenza virus 1, parainfluenza virus 2, parainfluenza virus 3, parainfluenza virus 4, respiratory syncytial virus, Bordetella pertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae. Two new targets are included in the FilmArray RP2: Middle East respiratory syndrome coronavirus and Bordetella parapertussis. This study provides data from a multicenter evaluation of 1,612 prospectively collected NPS samples, with performance compared to that of the FilmArray RP or PCR and sequencing. The overall percent agreement between the FilmArray RP2 and the comparator testing was 99.2%. The RP2 demonstrated a positive percent agreement of 91.7% or greater for detection of all but three analytes: coronavirus OC43, B. parapertussis, and B. pertussis. The FilmArray RP2 also demonstrated a negative percent agreement of ≥93.8% for all analytes. Of note, the adenovirus assay detects all genotypes, with a demonstrated increase in sensitivity. The FilmArray RP2 represents a significant improvement over the FilmArray RP, with a substantially shorter run time that could aid in the diagnosis of respiratory infections in a variety of clinical scenarios.",2018 May 25,"['Leber, Amy L.', 'Everhart, Kathy', 'Daly, Judy A.', 'Hopper, Aubrey', 'Harrington, Amanda', 'Schreckenberger, Paul', 'McKinley, Kathleen', 'Jones, Matthew', 'Holmberg, Kristen', 'Kensinger, Bart']",J Clin Microbiol,,,True
aad97e5900aad0319876f7467719cecf6a0e2f46,PMC,Multicenter Evaluation of BioFire FilmArray Respiratory Panel 2 for Detection of Viruses and Bacteria in Nasopharyngeal Swab Samples,http://dx.doi.org/10.1128/JCM.01945-17,PMC5971546,29593057,CC BY,"The FilmArray Respiratory Panel 2 (RP2) is a multiplex in vitro diagnostic test for the simultaneous and rapid (∼45-min) detection of 22 pathogens directly from nasopharyngeal swab (NPS) samples. It contains updated (and in some instances redesigned) assays that improve upon the FilmArray Respiratory Panel (RP; version 1.7), with a faster run time. The organisms identified are adenovirus, coronavirus 229E, coronavirus HKU1, coronavirus NL63, coronavirus OC43, human metapneumovirus, human rhinovirus/enterovirus, influenza virus A, influenza virus A H1, influenza virus A H1-2009, influenza virus A H3, influenza virus B, parainfluenza virus 1, parainfluenza virus 2, parainfluenza virus 3, parainfluenza virus 4, respiratory syncytial virus, Bordetella pertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae. Two new targets are included in the FilmArray RP2: Middle East respiratory syndrome coronavirus and Bordetella parapertussis. This study provides data from a multicenter evaluation of 1,612 prospectively collected NPS samples, with performance compared to that of the FilmArray RP or PCR and sequencing. The overall percent agreement between the FilmArray RP2 and the comparator testing was 99.2%. The RP2 demonstrated a positive percent agreement of 91.7% or greater for detection of all but three analytes: coronavirus OC43, B. parapertussis, and B. pertussis. The FilmArray RP2 also demonstrated a negative percent agreement of ≥93.8% for all analytes. Of note, the adenovirus assay detects all genotypes, with a demonstrated increase in sensitivity. The FilmArray RP2 represents a significant improvement over the FilmArray RP, with a substantially shorter run time that could aid in the diagnosis of respiratory infections in a variety of clinical scenarios.",2018 May 25,"['Leber, Amy L.', 'Everhart, Kathy', 'Daly, Judy A.', 'Hopper, Aubrey', 'Harrington, Amanda', 'Schreckenberger, Paul', 'McKinley, Kathleen', 'Jones, Matthew', 'Holmberg, Kristen', 'Kensinger, Bart']",J Clin Microbiol,,,False
d130fc09f47711585fbeec45605bb516380eb5c5,PMC,New Diagnosis of G6PD Deficiency Presenting as Severe Rhabdomyolysis,http://dx.doi.org/10.7759/cureus.2387,PMC5973499,29850382,CC BY,"A 24-year-old African-American man presented with malaise and low back pain and was found to have acute severe rhabdomyolysis followed by acute hemolysis. Glucose-6-phosphate dehydrogenase (G6PD) deficiency was suspected by the presence of blister cells on peripheral smear and was confirmed by a low enzyme activity assay. Our patient reported playing football, along with upper respiratory infection symptoms, prior to presentation. Extensive infectious and toxicology workup was negative; however, several inflammatory proteins were markedly elevated. We hypothesized the large inflammatory burden led to an increased reactive oxygen radical burden that overwhelmed muscle and erythrocyte reducing power. Severe rhabdomyolysis in G6PD deficiency is not a common presentation because skeletal muscles are more resistant to oxidative damage compared to red blood cells. Our case adds to the few existing reports of myolysis in the setting of G6PD deficiency.",,"['Eziokwu, Akaolisa S', 'Angelini, Dana']",Cureus.; 10(3):e2387,,,True
3e7cfb0f2665388e6a1f1d8a92b16d16f65563ea,PMC,Factors associated with changing indications for adenotonsillectomy: A population-based longitudinal study,http://dx.doi.org/10.1371/journal.pone.0193317,PMC5973846,29843158,CC BY,"OBJECTIVE: Adenotonsillectomy (AT) is one of the most common surgical procedures performed in children and adults. We aim to assess the factors associated with changes in the incidence of and indications for AT using population-level data. STUDY DESIGN: This retrospective cohort study investigated patients who underwent AT between 1997 and 2010 by using data from the Taiwan National Health Insurance Research Database. We examined surgical rates and indications by the calendar year as well as age, sex, hospital level, and insured residence areas for the correlating factors. RESULTS: The average annual incidence rate of AT was 14.7 per 100,000 individuals during 1997–2010. Pediatric (<18 years) patients represented 48.2% of the total AT population. More than 99% of the patients underwent the AT procedures as an inpatient intervention. Longitudinal data demonstrated an increasing trend in the pediatric AT rates from 1997 (4.3/100,000) to 2010 (5.7/100,000) (p = 0.029). In the adult subgroup, a decreasing prevalence of infectious indications (p = 0.014) coincided with an increasing neoplastic indications (p = 0.001). In the pediatric subgroup, the prevalence of obstructive indications increased (p = 0.002). The logistic regression analyses indicated that the significant factors associated with the changing surgical indications for AT were the age in the adult subgroup and hospital level in the pediatric subgroup. CONCLUSIONS: This study revealed a low AT rate in Taiwan than that in other countries. Pediatric AT incidence increased during 1997–2010. Although a rising prevalence of obstructive and neoplastic indications was noted, infection remained the most common indications for AT. Age in the adult subgroup and hospital level in the pediatric subgroup were factors associated with the changing indications for AT.",2018 May 29,"['Chen, Jeng-Wen', 'Liao, Po-Wu', 'Hsieh, Chi-Jeng', 'Chen, Chu-Chieh', 'Chiou, Shang-Jyh']",PLoS One,,,True
ed638b6b8897dfcc7b28ba26c2bb6048da0501e6,PMC,Burden of lower respiratory infections in the Eastern Mediterranean Region between 1990 and 2015: findings from the Global Burden of Disease 2015 study,http://dx.doi.org/10.1007/s00038-017-1007-0,PMC5973986,28776246,CC BY,"OBJECTIVES: We used data from the Global Burden of Disease 2015 study (GBD) to calculate the burden of lower respiratory infections (LRIs) in the 22 countries of the Eastern Mediterranean Region (EMR) from 1990 to 2015. METHODS: We conducted a systematic analysis of mortality and morbidity data for LRI and its specific etiologic factors, including pneumococcus, Haemophilus influenzae type b, Respiratory syncytial virus, and influenza virus. We used modeling methods to estimate incidence, deaths, and disability-adjusted life-years (DALYs). We calculated burden attributable to known risk factors for LRI. RESULTS: In 2015, LRIs were the fourth-leading cause of DALYs, causing 11,098,243 (95% UI 9,857,095–12,396,566) DALYs and 191,114 (95% UI 170,934–210,705) deaths. The LRI DALY rates were higher than global estimates in 2015. The highest and lowest age-standardized rates of DALYs were observed in Somalia and Lebanon, respectively. Undernutrition in childhood and ambient particulate matter air pollution in the elderly were the main risk factors. CONCLUSIONS: Our findings call for public health strategies to reduce the level of risk factors in each age group, especially vulnerable child and elderly populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00038-017-1007-0) contains supplementary material, which is available to authorized users.",2018 Aug 3,,Int J Public Health,,,True
810a3bc9ac8cca3ff39f3ad211f1d64549dce7e2,PMC,Homodimerisation-independent cleavage of dsRNA by a pestiviral nicking endoribonuclease,http://dx.doi.org/10.1038/s41598-018-26557-4,PMC5974291,29844335,CC BY,"The glycoprotein E(rns) plays a central role in the biology of the pestivirus bovine viral diarrhea virus (BVDV). This soluble endonuclease mediates the escape from an interferon (IFN) response in the infected fetus, thereby permitting the establishment of persistent infection. Viral single-stranded (ss) and double-stranded (ds) RNA act as potent IFN inducing signals and we previously showed that E(rns) efficiently cleaves these substrates, thereby inhibiting an IFN response that is crucial for successful fetal infection. Considering that a large variety of RNases and DNases require dimerisation to cleave double-stranded substrates, the activity of E(rns) against dsRNA was postulated to depend on homodimer formation mediated by disulfide bonds involving residue Cys171. Here, we show that monomeric E(rns) is equally able to cleave dsRNA and to inhibit dsRNA-induced IFN synthesis as the wild-type form. Furthermore, both forms were able to degrade RNA within a DNA/RNA- as well as within a methylated RNA/RNA-hybrid, with the DNA and the methylated RNA strand being resistant to degradation. These results support our model that E(rns) acts as ‘nicking endoribonuclease’ degrading ssRNA within double-stranded substrates. This efficiently prevents the activation of IFN and helps to maintain a state of innate immunotolerance in persistently infected animals.",2018 May 29,"['Lussi, Carmela', 'Sauter, Kay-Sara', 'Schweizer, Matthias']",Sci Rep,,,False
e18358325d65bee698980b7433a62923fcca051a,PMC,Homodimerisation-independent cleavage of dsRNA by a pestiviral nicking endoribonuclease,http://dx.doi.org/10.1038/s41598-018-26557-4,PMC5974291,29844335,CC BY,"The glycoprotein E(rns) plays a central role in the biology of the pestivirus bovine viral diarrhea virus (BVDV). This soluble endonuclease mediates the escape from an interferon (IFN) response in the infected fetus, thereby permitting the establishment of persistent infection. Viral single-stranded (ss) and double-stranded (ds) RNA act as potent IFN inducing signals and we previously showed that E(rns) efficiently cleaves these substrates, thereby inhibiting an IFN response that is crucial for successful fetal infection. Considering that a large variety of RNases and DNases require dimerisation to cleave double-stranded substrates, the activity of E(rns) against dsRNA was postulated to depend on homodimer formation mediated by disulfide bonds involving residue Cys171. Here, we show that monomeric E(rns) is equally able to cleave dsRNA and to inhibit dsRNA-induced IFN synthesis as the wild-type form. Furthermore, both forms were able to degrade RNA within a DNA/RNA- as well as within a methylated RNA/RNA-hybrid, with the DNA and the methylated RNA strand being resistant to degradation. These results support our model that E(rns) acts as ‘nicking endoribonuclease’ degrading ssRNA within double-stranded substrates. This efficiently prevents the activation of IFN and helps to maintain a state of innate immunotolerance in persistently infected animals.",2018 May 29,"['Lussi, Carmela', 'Sauter, Kay-Sara', 'Schweizer, Matthias']",Sci Rep,,,True
34e11e290d25709bbe4a448c970b54162f457902,PMC,Babesia vesperuginis in insectivorous bats from China,http://dx.doi.org/10.1186/s13071-018-2902-9,PMC5975495,29843764,CC BY,"BACKGROUND: To increase understanding of human bacterial and parasitic pathogens in bats, we investigated the prevalence of Babesia spp., Rickettsia spp., Anaplasma spp. and Coxiella burnetii in bats from China. METHODS: Bats were captured from Mengyin County, Shandong Province of China using nets. DNA was extracted from the blood and spleen of bats for molecular detection of Babesia spp., Rickettsia spp., Anaplasma spp. and Coxiella burnetii with specific primers for each species. RESULTS: A total of 146 spleen samples and 107 blood samples of insectivorous bats, which belonged to 6 species within two families, were collected from Mengyin County, Shandong Province of China. We found that two Eptesicus serotinus (2/15, 13.3%) were positive for Babesia vesperuginis. We were unable to detect genomic sequences for Rickettsia spp., Anaplasma spp. and Coxiella burnetii. CONCLUSIONS: To our knowledge, our study showed for the first time the presence of Babesia vesperuginis in Eptesicus serotinus collected from China, suggesting that Babesia vesperuginis has a broad host species and geographical distribution.",2018 May 29,"['Han, Hui-Ju', 'Liu, Jian-Wei', 'Wen, Hong-Ling', 'Qin, Xiang-Rong', 'Zhao, Min', 'Wang, Li-Jun', 'Zhou, Chuan-Min', 'Qi, Rui', 'Yu, Hao', 'Yu, Xue-Jie']",Parasit Vectors,,,True
57e168131391d871fa93444a1741f3f2b4403d45,PMC,Development of pooled testing system for porcine epidemic diarrhoea using real-time fluorescent reverse-transcription loop-mediated isothermal amplification assay,http://dx.doi.org/10.1186/s12917-018-1498-9,PMC5975689,29843733,CC BY,"BACKGROUND: Porcine epidemic diarrhoea (PED) is an emerging disease in pigs that causes massive economic losses in the swine industry, with high mortality in suckling piglets. Early identification of PED virus (PEDV)-infected herd through surveillance or monitoring strategies is necessary for mass control of PED. However, a common working diagnosis system involves identifying PEDV-infected animals individually, which is a costly and time-consuming approach. Given the above information, the thrusts of this study were to develop a real-time fluorescent reverse transcription loop-mediated isothermal amplification (RtF-RT-LAMP) assay and establish a pooled testing system using faecal sample to identify PEDV-infected herd. RESULTS: In this study, we developed an accurate, rapid, cost-effective, and simple RtF- RT-LAMP assay for detecting the PEDV genome targeting M gene. The pooled testing system using the RtF-RT-LAMP assay was optimized such that a pool of at least 15 individual faecal samples could be analysed. CONCLUSIONS: The developed RtF-RT-LAMP assay in our study could support the design and implementation of large-scaled epidemiological surveys as well as active surveillance and monitoring programs for effective control of PED. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1498-9) contains supplementary material, which is available to authorized users.",2018 May 29,"['Mai, Thi Ngan', 'Nguyen, Van Diep', 'Yamazaki, Wataru', 'Okabayashi, Tamaki', 'Mitoma, Shuya', 'Notsu, Kosuke', 'Sakai, Yuta', 'Yamaguchi, Ryoji', 'Norimine, Junzo', 'Sekiguchi, Satoshi']",BMC Vet Res,,,True
e60dc2f814db6256844444e573ea98bc9a9b4a93,PMC,Avian cholera outbreaks threaten seabird species on Amsterdam Island,http://dx.doi.org/10.1371/journal.pone.0197291,PMC5976148,29847561,CC BY,"Infectious diseases may be particularly critical for the conservation of endangered species. A striking example is the recurrent outbreaks that have been occurring in seabirds on Amsterdam Island for the past 30 years, threatening populations of three Endangered seabird species and of the endemic, Critically Endangered Amsterdam albatross Diomedea amsterdamensis. The bacteria Pasteurella multocida (avian cholera causative agent), and to a lesser extent Erysipelothrix rhusiopathiae (erysipelas causative agent), were both suspected to be responsible for these epidemics. Despite this critical situation, demographic trends were not available for these threatened populations, and the occurrence and characterization of potential causative agents of epizootics remain poorly known. The aims of the current study were to (i) provide an update of population trends for four threatened seabird species monitored on Amsterdam Island, (ii) assess the occurrence of P. multocida, and E. rhusiopathiae in live birds from five species, (iii) search for other infectious agents in these samples and, (iv) isolate and genotype the causative agent(s) of epizooties from dead birds. Our study shows that the demographic situation has worsened substantially in three seabird species during the past decade, with extremely low reproductive success and declining populations for Indian yellow-nosed albatrosses Thalassarche carteri, sooty albatrosses Phoebetria fusca, and northern rockhopper penguins Eudyptes moseleyi. Pasteurella multocida or E. rhusiopathiae were detected by PCR in live birds of all five investigated species, while results were negative for eight additional infectious agents. A single strain of P. multocida was repeatedly cultured from dead birds, while no E. rhusiopathiae could be isolated. These results highlight the significance of P. multocida in this particular eco-epidemiological system as the main agent responsible for epizootics. The study stresses the urgent need to implement mitigation measures to alter the course of avian cholera outbreaks threatening the persistence of seabird populations on Amsterdam Island.",2018 May 30,"['Jaeger, Audrey', 'Lebarbenchon, Camille', 'Bourret, Vincent', 'Bastien, Matthieu', 'Lagadec, Erwan', 'Thiebot, Jean-Baptiste', 'Boulinier, Thierry', 'Delord, Karine', 'Barbraud, Christophe', 'Marteau, Cédric', 'Dellagi, Koussay', 'Tortosa, Pablo', 'Weimerskirch, Henri']",PLoS One,,,True
944f574a3d37e76e4d5a5d23c870733622b02dc9,PMC,An evaluation of emergency guidelines issued by the World Health Organization in response to four infectious disease outbreaks,http://dx.doi.org/10.1371/journal.pone.0198125,PMC5976182,29847593,CC BY,"BACKGROUND: The production of high-quality guidelines in response to public health emergencies poses challenges for the World Health Organization (WHO). The urgent need for guidance and the paucity of structured scientific data on emerging diseases hinder the formulation of evidence-informed recommendations using standard methods and procedures. OBJECTIVES: In the context of the response to recent public health emergencies, this project aimed to describe the information products produced by WHO and assess the quality and trustworthiness of a subset of these products classified as guidelines. METHODS: We selected four recent infectious disease emergencies: outbreaks of avian influenza A—H1N1 virus (2009) and H7N9 virus (2013), Middle East respiratory syndrome coronavirus (MERS-CoV) (2013), and Ebola virus disease (EVD) (2014 to 2016). We analyzed the development and publication processes and evaluated the quality of emergency guidelines using AGREE-II. RESULTS: We included 175 information products of which 87 were guidelines. These products demonstrated variable adherence to WHO publication requirements including the listing of external contributors, management of declarations of interest, and entry into WHO’s public database of publications. For guidelines, the methods for development were incompletely reported; WHO’s quality assurance process was rarely used; systematic or other evidence reviews were infrequently referenced; external peer review was not performed; and they scored poorly with AGREE II, particularly for rigour of development and editorial independence. CONCLUSIONS: Our study suggests that WHO guidelines produced in the context of a public health emergency can be improved upon, helping to assure the trustworthiness and utility of WHO information products in future emergencies.",2018 May 30,"['Norris, Susan L.', 'Sawin, Veronica Ivey', 'Ferri, Mauricio', 'Raques Sastre, Laura', 'Porgo, Teegwendé V.']",PLoS One,,,True
a2e2beb6ce9597d9a4162f1399ed1a92cc010b66,PMC,Zika Virus Induces Autophagy in Human Umbilical Vein Endothelial Cells,http://dx.doi.org/10.3390/v10050259,PMC5977252,29762492,CC BY,"Autophagy is a common strategy for cell protection; however, some viruses can in turn adopt cellular autophagy to promote viral replication. Zika virus (ZIKV) is the pathogen that causes Zika viral disease, and it is a mosquito-borne virus. However, its pathogenesis, especially the interaction between ZIKV and target cells during the early stages of infection, is still unclear. In this study, we demonstrate that infecting human umbilical vein endothelial cells (HUVEC) with ZIKV triggers cellular autophagy. We observed both an increase in the conversion of LC3-I to LC3-II and increased accumulation of fluorescent cells with LC3 dots, which are considered to be the two key indicators of autophagy. The ratio of LC3-II/GAPDH in each group was significantly increased at different times after ZIKV infection at different MOIs, indicating that the production of lipidated LC3-II increased. Moreover, both the ratio of LC3-II/GAPDH and the expression of viral NS3 protein increased with increasing time of viral infection. The expression level of p62 decreased gradually from 12 h post-infection. Expression profile of double fluorescent protein labelling LC3 indicated that the autophagy induced by ZIKV infection was a complete process. We further investigated the role of autophagy in ZIKV replication. We demonstrated that either the treatment with inhibitors of autophagosomes formation or short hairpin RNA targeting the Beclin-1 gene, which is critical for the formation of autophagosomes, significantly reduced viral production. Taken together, our results indicate that ZIKV infection induces autophagy of HUVEC, and inhibition of ZIKV-induced autophagy restrains viral replication.",2018 May 15,"['Peng, Haoran', 'Liu, Bin', 'Yves, Toure Doueu', 'He, Yanhua', 'Wang, Shijie', 'Tang, Hailin', 'Ren, Hao', 'Zhao, Ping', 'Qi, Zhongtian', 'Qin, Zhaoling']",Viruses,,,True
daf5c921872ab27dc1a714408f626f49c71480e1,PMC,Strain-Specific Antagonism of the Human H1N1 Influenza A Virus against Equine Tetherin,http://dx.doi.org/10.3390/v10050264,PMC5977257,29772683,CC BY,"Tetherin/BST-2/CD317 is an interferon-induced host restriction factor that can block the budding of enveloped viruses by tethering them to the cell surface. Many viruses use certain proteins to counteract restriction by tetherin from their natural hosts, but not from other species. The influenza A virus (FLUAV) has a wide range of subtypes with different host tropisms. Human tetherin (huTHN) has been reported to restrict only specific FLUAV strains and the viral hemagglutinin (HA) and neuraminidase (NA) genes determine the sensitivity to huTHN. Whether tetherins from other hosts can block human FLUAV is still unknown. Here, we evaluate the impact of equine tetherin (eqTHN) and huTHN on the replication of A/Sichuan/1/2009 (H1N1) and A/equine/Xinjiang/1/2007 (H3N8) strains. Our results show that eqTHN had higher restriction activity towards both viruses, and its shorter cytoplasmic tail contributed to that activity. We further demonstrated that HA and NA of A/Hamburg/4/2009 (H1N1) could counteract eqTHN. Notably, our results indicate that four amino acids, 13T and 49L of HA and 32T and 80V of NA, were involved in blocking the restriction activity of eqTHN. These findings reveal interspecies restriction by eqTHN towards FLUAV, and the role of the HA and NA proteins in overcoming this restriction.",2018 May 16,"['Wang, Meiyue', 'Zhang, Zhenyu', 'Wang, Xiaojun']",Viruses,,,True
bd067c850dd16252d8c195caeb129a3e304e5700,PMC,Inhibition of Human Immunodeficiency Virus Type 1 Entry by a Keggin Polyoxometalate,http://dx.doi.org/10.3390/v10050265,PMC5977258,29772712,CC BY,"Here, we report the anti-human immunodeficiency virus (HIV) potency and underlying mechanisms of a Keggin polyoxometalate (PT-1, K(6)HPTi(2)W(10)O(40)). Our findings showed that PT-1 exhibited highly potent effects against a diverse group of HIV type 1 (HIV-1) strains and displayed low cytotoxicity and genotoxicity. The time-addition assay revealed that PT-1 acted at an early stage of infection, and these findings were supported by the observation that PT-1 had more potency against Env-pseudotyped virus than vesicular stomatitis virus glycoprotein (VSVG) pseudotyped virus. Surface plasmon resonance binding assays and flow cytometry analysis showed that PT-1 blocked the gp120 binding site in the CD4 receptor. Moreover, PT-1 bound directly to gp41 NHR (N36 peptide), thereby interrupting the core bundle formation of gp41. In conclusion, our data suggested that PT-1 may be developed as a new anti-HIV-1 agent through its effects on entry inhibition.",2018 May 16,"['Wang, Xiaoli', 'Wang, Jiao', 'Zhang, Wenmei', 'Li, Boye', 'Zhu, Ying', 'Hu, Qin', 'Yang, Yishu', 'Zhang, Xiaoguang', 'Yan, Hong', 'Zeng, Yi']",Viruses,,,True
7cb88bf8c6103b71c0a6a538fc5ee7adee629d7e,PMC,Inhibition of Human Immunodeficiency Virus Type 1 Entry by a Keggin Polyoxometalate,http://dx.doi.org/10.3390/v10050265,PMC5977258,29772712,CC BY,"Here, we report the anti-human immunodeficiency virus (HIV) potency and underlying mechanisms of a Keggin polyoxometalate (PT-1, K(6)HPTi(2)W(10)O(40)). Our findings showed that PT-1 exhibited highly potent effects against a diverse group of HIV type 1 (HIV-1) strains and displayed low cytotoxicity and genotoxicity. The time-addition assay revealed that PT-1 acted at an early stage of infection, and these findings were supported by the observation that PT-1 had more potency against Env-pseudotyped virus than vesicular stomatitis virus glycoprotein (VSVG) pseudotyped virus. Surface plasmon resonance binding assays and flow cytometry analysis showed that PT-1 blocked the gp120 binding site in the CD4 receptor. Moreover, PT-1 bound directly to gp41 NHR (N36 peptide), thereby interrupting the core bundle formation of gp41. In conclusion, our data suggested that PT-1 may be developed as a new anti-HIV-1 agent through its effects on entry inhibition.",2018 May 16,"['Wang, Xiaoli', 'Wang, Jiao', 'Zhang, Wenmei', 'Li, Boye', 'Zhu, Ying', 'Hu, Qin', 'Yang, Yishu', 'Zhang, Xiaoguang', 'Yan, Hong', 'Zeng, Yi']",Viruses,,,False
a2707740419f3f999535e908845471d220054dfb,PMC,Therapeutic Potential of Annexin A1 in Ischemia Reperfusion Injury,http://dx.doi.org/10.3390/ijms19041211,PMC5979321,29659553,CC BY,"Cardiovascular disease (CVD) continues to be the leading cause of death in the world. Increased inflammation and an enhanced thrombotic milieu represent two major complications of CVD, which can culminate into an ischemic event. Treatment for these life-threatening complications remains reperfusion and restoration of blood flow. However, reperfusion strategies may result in ischemia–reperfusion injury (I/RI) secondary to various cardiovascular pathologies, including myocardial infarction and stroke, by furthering the inflammatory and thrombotic responses and delivering inflammatory mediators to the affected tissue. Annexin A1 (AnxA1) and its mimetic peptides are endogenous anti-inflammatory and pro-resolving mediators, known to have significant effects in resolving inflammation in a variety of disease models. Mounting evidence suggests that AnxA1, which interacts with the formyl peptide receptor (FPR) family, may have a significant role in mitigating I/RI associated complications. In this review article, we focus on how AnxA1 plays a protective role in the I/R based vascular pathologies.",2018 Apr 16,"['Ansari, Junaid', 'Kaur, Gaganpreet', 'Gavins, Felicity N. E.']",Int J Mol Sci,,,True
96cb8642bc772cbc519af39243eec2809cbba57e,PMC,DDX5 RNA Helicases: Emerging Roles in Viral Infection,http://dx.doi.org/10.3390/ijms19041122,PMC5979547,29642538,CC BY,"Asp-Glu-Ala-Asp (DEAD)-box polypeptide 5 (DDX5), also called p68, is a prototypical member of the large ATP-dependent RNA helicases family and is known to participate in all aspects of RNA metabolism ranging from transcription to translation, RNA decay, and miRNA processing. The roles of DDX5 in cell cycle regulation, tumorigenesis, apoptosis, cancer development, adipogenesis, Wnt-β-catenin signaling, and viral infection have been established. Several RNA viruses have been reported to hijack DDX5 to facilitate various steps of their replication cycles. Furthermore, DDX5 can be bounded by the viral proteins of some viruses with unknown functions. Interestingly, an antiviral function of DDX5 has been reported during hepatitis B virus and myxoma virus infection. Thus, the precise roles of this apparently multifaceted protein remain largely obscure. Here, we provide a rapid and critical overview of the structure and functions of DDX5 with a particular emphasis on its role during virus infection.",2018 Apr 9,"['Cheng, Wenyu', 'Chen, Guohua', 'Jia, Huaijie', 'He, Xiaobing', 'Jing, Zhizhong']",Int J Mol Sci,,,True
23f1565e1f4f6a5e0c92d96dc454299a9e37400b,PMC,"Oxymatrine Inhibits Influenza A Virus Replication and Inflammation via TLR4, p38 MAPK and NF-κB Pathways",http://dx.doi.org/10.3390/ijms19040965,PMC5979549,29570670,CC BY,"Oxymatrine (OMT) is a strong immunosuppressive agent that has been used in the clinic for many years. In the present study, by using plaque inhibition, luciferase reporter plasmids, qRT-PCR, western blotting, and ELISA assays, we have investigated the effect and mechanism of OMT on influenza A virus (IAV) replication and IAV-induced inflammation in vitro and in vivo. The results showed that OMT had excellent anti-IAV activity on eight IAV strains in vitro. OMT could significantly decrease the promoter activity of TLR3, TLR4, TLR7, MyD88, and TRAF6 genes, inhibit IAV-induced activations of Akt, ERK1/2, p38 MAPK, and NF-κB pathways, and suppress the expressions of inflammatory cytokines and MMP-2/-9. Activators of TLR4, p38 MAPK and NF-κB pathways could significantly antagonize the anti-IAV activity of OMT in vitro, including IAV replication and IAV-induced cytopathogenic effect (CPE). Furthermore, OMT could reduce the loss of body weight, significantly increase the survival rate of IAV-infected mice, decrease the lung index, pulmonary inflammation and lung viral titter, and improve pulmonary histopathological changes. In conclusion, OMT possesses anti-IAV and anti-inflammatory activities, the mechanism of action may be linked to its ability to inhibit IAV-induced activations of TLR4, p38 MAPK, and NF-κB pathways.",2018 Mar 23,"['Dai, Jian-Ping', 'Wang, Qian-Wen', 'Su, Yun', 'Gu, Li-Ming', 'Deng, Hui-Xiong', 'Chen, Xiao-Xuan', 'Li, Wei-Zhong', 'Li, Kang-Sheng']",Int J Mol Sci,,,True
de652a9f987a68568c425859c662ea8d2325631c,PMC,"Outbreak of porcine epidemic diarrhoea virus (PEDV) in Abruzzi region, central‐Italy",http://dx.doi.org/10.1002/vms3.88,PMC5979762,29851308,CC BY,"Here we report and characterize a porcine epidemic diarrhea (PED) outbreak which occurred in a swine fattening farm in the province of Teramo, Abruzzi region (central Italy), in January 2016. PED virus (PEDV) identification was determined by real‐time RT‐PCR performed on RNAs purified from fecal samples collected from two symptomatic pigs. Whole genome sequence (PEDV 1842/2016) was also obtained by next generation sequencing straight from RNA purified from one fecal sample. Genome comparison with extant global PEDV strains revealed a high nucleotide identity with recently reported European and American S‐INDEL PEDVs. Efficient sequencing, share of genomic data combined with the implementation of epidemiological tools would be the ideal approach for study and analysis of transboundary infectious diseases as PED.",2017 Dec 18,"['Pizzurro, Federica', 'Cito, Francesca', 'Zaccaria, Guendalina', 'Spedicato, Massimo', 'Cerella, Angelo', 'Orsini, Massimiliano', 'Forzan, Mario', ""D'Alterio, Nicola"", 'Lorusso, Alessio', 'Marcacci, Maurilia']",Vet Med Sci,,,True
44b6af6bcf205a0a6c91aee80d9b67e0f4e226ae,PMC,Complete Genome Sequences of Four Bovine Coronavirus Isolates from Pennsylvania,http://dx.doi.org/10.1128/genomeA.00467-18,PMC5981048,29853507,CC BY,"We report four full-genome sequences of bovine coronavirus (BCoV) isolates from dairy calves in Pennsylvania obtained in 2016 and 2017. BCoV is a pathogen of great importance to cattle health, and this is the first report of full-genome sequences of BCoV from PA cattle.",2018 May 31,"['Byukusenge, Maurice', 'Nissly, Ruth Helmus', 'Kasibhatla, Sunitha Manjari', 'Li, Lingling', 'Russell, Rebekah', 'Springer, Hayley', 'Barry, Rhiannon', 'Van Saun, Robert', 'Wolfgang, David', 'Hovingh, Ernest', 'Kulkarni-Kale, Urmila', 'Kuchipudi, Suresh V.']",Genome Announc,,,True
011b8a7002da6c0fae7ca76c127567a6462daf5d,PMC,"Survival of the Enveloped Virus Phi6 in Droplets as a Function of Relative Humidity, Absolute Humidity, and Temperature",http://dx.doi.org/10.1128/AEM.00551-18,PMC5981065,29625986,CC BY,"Infectious diseases caused by enveloped viruses, such as influenza, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS), cause thousands of deaths and billions of dollars of economic losses per year. Studies have found a relationship among temperature, humidity, and influenza virus incidence, transmission, or survival; however, there are contradictory claims about whether absolute humidity (AH) or relative humidity (RH) is most important in mediating virus infectivity. Using the enveloped bacteriophage Phi6, which has been suggested as a surrogate for influenza viruses and coronaviruses, we designed a study to discern whether AH, RH, or temperature is a better predictor of virus survival in droplets. Our results show that Phi6 survived best at high (>85%) and low (<60%) RHs, with a significant decrease in infectivity at mid-range RHs (∼60 to 85%). At an AH of less than 22 g · m(−3), the loss in infectivity was less than 2 orders of magnitude; however, when the AH was greater than 22 g · m(−3), the loss in infectivity was typically greater than 6 orders of magnitude. At a fixed RH of 75%, infectivity was very sensitive to temperature, decreasing two orders of magnitude between 19°C and 25°C. We used random forest modeling to identify the best environmental predictors for modulating virus infectivity. The model explained 83% of variation in Phi6 infectivity and suggested that RH is the most important factor in controlling virus infectivity in droplets. This research provides novel information about the complex interplay between temperature, humidity, and the survival of viruses in droplets. IMPORTANCE Enveloped viruses are responsible for a number of infectious diseases resulting in thousands of deaths and billions of dollars of economic losses per year in the United States. There has been a lively debate in the literature over whether absolute humidity (AH) or relative humidity (RH) modulates virus infectivity. We designed a controlled study and used advanced statistical modeling techniques specifically to address this question. By providing an improved understanding of the relationship between environmental conditions and virus infectivity, our work will ultimately lead to improved strategies for predicting and controlling disease transmission.",2018 May 31,"['Prussin, Aaron J.', 'Schwake, David Otto', 'Lin, Kaisen', 'Gallagher, Daniel L.', 'Buttling, Lauren', 'Marr, Linsey C.']",Appl Environ Microbiol,,,True
e6338aaa400a0080f7189298a977daf80d91896c,PMC,Tetraspanin Assemblies in Virus Infection,http://dx.doi.org/10.3389/fimmu.2018.01140,PMC5981178,29887866,CC BY,"Tetraspanins (Tspans) are a family of four-span transmembrane proteins, known as plasma membrane “master organizers.” They form Tspan-enriched microdomains (TEMs or TERMs) through lateral association with one another and other membrane proteins. If multiple microdomains associate with each other, larger platforms can form. For infection, viruses interact with multiple cell surface components, including receptors, activating proteases, and signaling molecules. It appears that Tspans, such as CD151, CD82, CD81, CD63, CD9, Tspan9, and Tspan7, coordinate these associations by concentrating the interacting partners into Tspan platforms. In addition to mediating viral attachment and entry, these platforms may also be involved in intracellular trafficking of internalized viruses and assist in defining virus assembly and exit sites. In conclusion, Tspans play a role in viral infection at different stages of the virus replication cycle. The present review highlights recently published data on this topic, with a focus on events at the plasma membrane. In light of these findings, we propose a model for how Tspan interactions may organize cofactors for viral infection into distinct molecular platforms.",2018 May 25,"['Florin, Luise', 'Lang, Thorsten']",Front Immunol,,,True
7608309e163c6a51f211cc02d6e34659feb64418,PMC,Chlamydia trachomatis-infected cells and uninfected-bystander cells exhibit diametrically opposed responses to interferon gamma,http://dx.doi.org/10.1038/s41598-018-26765-y,PMC5981614,29855501,CC BY,"The intracellular bacterial pathogen, Chlamydia trachomatis, is a tryptophan auxotroph. Therefore, induction of the host tryptophan catabolizing enzyme, indoleamine-2,3-dioxgenase-1 (IDO1), by interferon gamma (IFNγ) is one of the primary protective responses against chlamydial infection. However, despite the presence of a robust IFNγ response, active and replicating C. trachomatis can be detected in cervical secretions of women. We hypothesized that a primary C. trachomatis infection may evade the IFNγ response, and that the protective effect of this cytokine results from its activation of tryptophan catabolism in bystander cells. To test this hypothesis, we developed a novel method to separate a pool of cells exposed to C. trachomatis into pure populations of live infected and bystander cells and applied this technique to distinguish between the effects of IFNγ on infected and bystander cells. Our findings revealed that the protective induction of IDO1 is suppressed specifically within primary infected cells because Chlamydia attenuates the nuclear import of activated STAT1 following IFNγ exposure, without affecting STAT1 levels or phosphorylation. Critically, the IFNγ-mediated induction of IDO1 activity is unhindered in bystander cells. Therefore, the IDO1-mediated tryptophan catabolism is functional in these cells, transforming these bystander cells into inhospitable hosts for a secondary C. trachomatis infection.",2018 May 31,"['Ibana, Joyce A.', 'Sherchand, Shardulendra P.', 'Fontanilla, Francis L.', 'Nagamatsu, Takeshi', 'Schust, Danny J.', 'Quayle, Alison J.', 'Aiyar, Ashok']",Sci Rep,,,False
e1684d4ad73d5982451ae73e97542c2559c04038,PMC,Chlamydia trachomatis-infected cells and uninfected-bystander cells exhibit diametrically opposed responses to interferon gamma,http://dx.doi.org/10.1038/s41598-018-26765-y,PMC5981614,29855501,CC BY,"The intracellular bacterial pathogen, Chlamydia trachomatis, is a tryptophan auxotroph. Therefore, induction of the host tryptophan catabolizing enzyme, indoleamine-2,3-dioxgenase-1 (IDO1), by interferon gamma (IFNγ) is one of the primary protective responses against chlamydial infection. However, despite the presence of a robust IFNγ response, active and replicating C. trachomatis can be detected in cervical secretions of women. We hypothesized that a primary C. trachomatis infection may evade the IFNγ response, and that the protective effect of this cytokine results from its activation of tryptophan catabolism in bystander cells. To test this hypothesis, we developed a novel method to separate a pool of cells exposed to C. trachomatis into pure populations of live infected and bystander cells and applied this technique to distinguish between the effects of IFNγ on infected and bystander cells. Our findings revealed that the protective induction of IDO1 is suppressed specifically within primary infected cells because Chlamydia attenuates the nuclear import of activated STAT1 following IFNγ exposure, without affecting STAT1 levels or phosphorylation. Critically, the IFNγ-mediated induction of IDO1 activity is unhindered in bystander cells. Therefore, the IDO1-mediated tryptophan catabolism is functional in these cells, transforming these bystander cells into inhospitable hosts for a secondary C. trachomatis infection.",2018 May 31,"['Ibana, Joyce A.', 'Sherchand, Shardulendra P.', 'Fontanilla, Francis L.', 'Nagamatsu, Takeshi', 'Schust, Danny J.', 'Quayle, Alison J.', 'Aiyar, Ashok']",Sci Rep,,,True
2cb1a471e9f1ba5fe1623c8143f8847c0b12dbe6,PMC,"Campylobacteriosis, Salmonellosis, Yersiniosis, and Listeriosis as Zoonotic Foodborne Diseases: A Review",http://dx.doi.org/10.3390/ijerph15050863,PMC5981902,29701663,CC BY,"Zoonoses are diseases transmitted from animals to humans, posing a great threat to the health and life of people all over the world. According to WHO estimations, 600 million cases of diseases caused by contaminated food were noted in 2010, including almost 350 million caused by pathogenic bacteria. Campylobacter, Salmonella, as well as Yersinia enterocolitica and Listeria monocytogenes may dwell in livestock (poultry, cattle, and swine) but are also found in wild animals, pets, fish, and rodents. Animals, often being asymptomatic carriers of pathogens, excrete them with faeces, thus delivering them to the environment. Therefore, pathogens may invade new individuals, as well as reside on vegetables and fruits. Pathogenic bacteria also penetrate food production areas and may remain there in the form of a biofilm covering the surfaces of machines and equipment. A common occurrence of microbes in food products, as well as their improper or careless processing, leads to common poisonings. Symptoms of foodborne infections may be mild, sometimes flu-like, but they also may be accompanied by severe complications, some even fatal. The aim of the paper is to summarize and provide information on campylobacteriosis, salmonellosis, yersiniosis, and listeriosis and the aetiological factors of those diseases, along with the general characteristics of pathogens, virulence factors, and reservoirs.",2018 May 26,"['Chlebicz, Agnieszka', 'Śliżewska, Katarzyna']",Int J Environ Res Public Health,,,True
3f9b24ea368416ce33708bb28327fb0b686b0ef0,PMC,Counting Down the 2020 Goals for 9 Neglected Tropical Diseases: What Have We Learned From Quantitative Analysis and Transmission Modeling?,http://dx.doi.org/10.1093/cid/ciy284,PMC5982793,29860293,CC BY,"The control of neglected tropical diseases (NTDs) has received huge investment in recent years, leading to large reductions in morbidity. In 2012, the World Health Organization set ambitious targets for eliminating many of these diseases as a public health problem by 2020, an aspiration that was supported by donations of treatments, intervention materials, and funding committed by a broad partnership of stakeholders in the London Declaration on NTDs. Alongside these efforts, there has been an increasing role for quantitative analysis and modeling to support the achievement of these goals through evaluation of the likely impact of interventions, the factors that could undermine these achievements, and the role of new diagnostics and treatments in reducing transmission. In this special issue, we aim to summarize those insights in an accessible way. This article acts as an introduction to the special issue, outlining key concepts in NTDs and insights from modeling as we approach 2020.",2018 Jun 15,"Hollingsworth, T Déirdre",Clin Infect Dis,,,True
d30e8b7dea667b484ce677f10755c971beff8e17,PMC,"Galactose-1-phosphate uridyltransferase (GalT), an in vivo-induced antigen of Actinobacillus pleuropneumoniae serovar 5b strain L20, provided immunoprotection against serovar 1 strain MS71",http://dx.doi.org/10.1371/journal.pone.0198207,PMC5983418,29856812,CC BY,"GALT is an important antigen of Actinobacillus pleuropneumoniae (APP), which was shown to provide partial protection against APP infection in a previous study in our lab. The main purpose of the present study is to investigate GALT induced cross-protection between different APP serotypes and elucidate key mechanisms of the immune response to GALT antigenic stimulation. Bioinformatic analysis demonstrated that galT is a highly conserved gene in APP, widely distributed across multiple pathogenic strains. Homologies between any two strains ranges from 78.9% to 100% regarding the galT locus. Indirect enzyme-linked immunosorbent assay (ELISA) confirmed that GALT specific antibodies could not be induced by inactivated APP L20 or MS71 whole cell bacterin preparations. A recombinant fusion GALT protein derived from APP L20, however has proven to be an effective cross-protective antigen against APP sevorar 1 MS71 (50%, 4/8) and APP sevorar 5b L20 (75%, 6/8). Histopathological examinations have confirmed that recombinant GALT vaccinated animals showed less severe pathological signs in lung tissues than negative controls after APP challenge. Immunohistochemical (IHC) analysis indicated that the infiltration of neutrophils in the negative group is significantly increased compared with that in the normal control (P<0.001) and that in surviving animals is decreased compared to the negative group. Anti-GALT antibodies were shown to mediate phagocytosis of neutrophils. After interaction with anti-GALT antibodies, survival rate of APP challenged vaccinated animals was significantly reduced (P<0.001). This study demonstrated that GALT is an effective cross-protective antigen, which could be used as a potential vaccine candidate against multiple APP serotypes.",2018 Jun 1,"['Zhang, Fei', 'Zhao, Qin', 'Quan, Keji', 'Zhu, Zhuang', 'Yang, Yusheng', 'Wen, Xintian', 'Chang, Yung-Fu', 'Huang, Xiaobo', 'Wu, Rui', 'Wen, Yiping', 'Yan, Qigui', 'Huang, Yong', 'Ma, Xiaoping', 'Han, Xinfeng', 'Cao, Sanjie']",PLoS One,,,True
de9149c42039c1d4787601b26e5d9d93174da17e,PMC,"Galactose-1-phosphate uridyltransferase (GalT), an in vivo-induced antigen of Actinobacillus pleuropneumoniae serovar 5b strain L20, provided immunoprotection against serovar 1 strain MS71",http://dx.doi.org/10.1371/journal.pone.0198207,PMC5983418,29856812,CC BY,"GALT is an important antigen of Actinobacillus pleuropneumoniae (APP), which was shown to provide partial protection against APP infection in a previous study in our lab. The main purpose of the present study is to investigate GALT induced cross-protection between different APP serotypes and elucidate key mechanisms of the immune response to GALT antigenic stimulation. Bioinformatic analysis demonstrated that galT is a highly conserved gene in APP, widely distributed across multiple pathogenic strains. Homologies between any two strains ranges from 78.9% to 100% regarding the galT locus. Indirect enzyme-linked immunosorbent assay (ELISA) confirmed that GALT specific antibodies could not be induced by inactivated APP L20 or MS71 whole cell bacterin preparations. A recombinant fusion GALT protein derived from APP L20, however has proven to be an effective cross-protective antigen against APP sevorar 1 MS71 (50%, 4/8) and APP sevorar 5b L20 (75%, 6/8). Histopathological examinations have confirmed that recombinant GALT vaccinated animals showed less severe pathological signs in lung tissues than negative controls after APP challenge. Immunohistochemical (IHC) analysis indicated that the infiltration of neutrophils in the negative group is significantly increased compared with that in the normal control (P<0.001) and that in surviving animals is decreased compared to the negative group. Anti-GALT antibodies were shown to mediate phagocytosis of neutrophils. After interaction with anti-GALT antibodies, survival rate of APP challenged vaccinated animals was significantly reduced (P<0.001). This study demonstrated that GALT is an effective cross-protective antigen, which could be used as a potential vaccine candidate against multiple APP serotypes.",2018 Jun 1,"['Zhang, Fei', 'Zhao, Qin', 'Quan, Keji', 'Zhu, Zhuang', 'Yang, Yusheng', 'Wen, Xintian', 'Chang, Yung-Fu', 'Huang, Xiaobo', 'Wu, Rui', 'Wen, Yiping', 'Yan, Qigui', 'Huang, Yong', 'Ma, Xiaoping', 'Han, Xinfeng', 'Cao, Sanjie']",PLoS One,,,False
b5e34eba97146683125dfee8f488fbc6bd9e06c8,PMC,"Galactose-1-phosphate uridyltransferase (GalT), an in vivo-induced antigen of Actinobacillus pleuropneumoniae serovar 5b strain L20, provided immunoprotection against serovar 1 strain MS71",http://dx.doi.org/10.1371/journal.pone.0198207,PMC5983418,29856812,CC BY,"GALT is an important antigen of Actinobacillus pleuropneumoniae (APP), which was shown to provide partial protection against APP infection in a previous study in our lab. The main purpose of the present study is to investigate GALT induced cross-protection between different APP serotypes and elucidate key mechanisms of the immune response to GALT antigenic stimulation. Bioinformatic analysis demonstrated that galT is a highly conserved gene in APP, widely distributed across multiple pathogenic strains. Homologies between any two strains ranges from 78.9% to 100% regarding the galT locus. Indirect enzyme-linked immunosorbent assay (ELISA) confirmed that GALT specific antibodies could not be induced by inactivated APP L20 or MS71 whole cell bacterin preparations. A recombinant fusion GALT protein derived from APP L20, however has proven to be an effective cross-protective antigen against APP sevorar 1 MS71 (50%, 4/8) and APP sevorar 5b L20 (75%, 6/8). Histopathological examinations have confirmed that recombinant GALT vaccinated animals showed less severe pathological signs in lung tissues than negative controls after APP challenge. Immunohistochemical (IHC) analysis indicated that the infiltration of neutrophils in the negative group is significantly increased compared with that in the normal control (P<0.001) and that in surviving animals is decreased compared to the negative group. Anti-GALT antibodies were shown to mediate phagocytosis of neutrophils. After interaction with anti-GALT antibodies, survival rate of APP challenged vaccinated animals was significantly reduced (P<0.001). This study demonstrated that GALT is an effective cross-protective antigen, which could be used as a potential vaccine candidate against multiple APP serotypes.",2018 Jun 1,"['Zhang, Fei', 'Zhao, Qin', 'Quan, Keji', 'Zhu, Zhuang', 'Yang, Yusheng', 'Wen, Xintian', 'Chang, Yung-Fu', 'Huang, Xiaobo', 'Wu, Rui', 'Wen, Yiping', 'Yan, Qigui', 'Huang, Yong', 'Ma, Xiaoping', 'Han, Xinfeng', 'Cao, Sanjie']",PLoS One,,,False
215e667edcc02054361258755a4db8bca18a4e9b,PMC,Public health education at China’s higher education institutions: a time-series analysis from 1998 to 2012,http://dx.doi.org/10.1186/s12889-018-5605-4,PMC5984438,29855370,CC BY,"BACKGROUND: Although China’s modern education for public health was developing over the past 60 years, there is a lack of authoritative statistics and analyses on the nation’s development of education for public health at higher education institutions (HEIs). Few quantitative studies on this topic have been published in domestic and international peer-reviewed journals. To address this knowledge gap, we aimed to use national data to quantitatively analyse the scale, structure, and changes of public health education in China’s HEIs, and to compare the changes of public health education with those of other health science disciplines. METHODS: This study uses previously unreleased national data provided by the Ministry of Education of China that includes the number of health professional students by school and major. The data, which spans from 1998 to 2012, are descriptively analyzed. RESULTS: The number of HEIs for public health education per 100 million population increased from 7.2 in 1998 to 11.3 in 2012. The total enrolment, number of students, and number of graduates increased at rates of 7.3, 7.4, and 5.8% per year, respectively. The percentage of junior college students dropped drastically from 24.0 to 8.4% from 1998 to 2012. During that same period, the number of undergraduates, master and doctorate students increased. Undergraduates accounted for the majority of public health graduates (63.1%) in 2012, and master and doctorate students increased by 10.0 and 5.1 times, respectively, from 1998 to 2012. The relative percentage of public health enrollment, students, and graduates to all health education disciplines dropped from about 6.0% percent in 1998 to around 2% in 2012. CONCLUSIONS: The overall scale of public health education has clearly expanded, though at a slower pace than many other health science disciplines in China. The increase of public health graduates helped to address the previous shortage of public health professionals. Gradually adopting a modern model of education, public health education in China has undergone notable changes that may be informative to other developing countries though it still faces a complex situation in terms of graduates’ adherence to public health, student recruitment, teaching and training, program planning and reform.",2018 May 31,"['Hou, Jianlin', 'Wang, Zhifeng', 'Liu, Xiaoyun', 'Luo, Youhui', 'Sabharwal, Sabhyta', 'Wang, Nan', 'Meng, Qingyue']",BMC Public Health,,,True
648043eabf0ac87a2bd28909cd4a739f8b2c4a35,PMC,High Shedding Potential and Significant Individual Heterogeneity in Naturally-Infected Alpine ibex (Capra ibex) With Brucella melitensis,http://dx.doi.org/10.3389/fmicb.2018.01065,PMC5985404,29892274,CC BY,"Wildlife reservoirs of infectious diseases raise major management issues. In Europe, brucellosis has been eradicated in domestic ruminants from most countries and wild ruminants have not been considered important reservoirs so far. However, a high prevalence of Brucella melitensis infection has been recently identified in a French population of Alpine ibex (Capra ibex), after the emergence of brucellosis was confirmed in a dairy cattle farm and two human cases. This situation raised the need to identify the factors driving the persistence of Brucella infection at high prevalence levels in this ibex population. In the present paper, we studied the shedding pattern of B. melitensis in ibex from Bargy Massif, French Alps. Bacteriological examinations (1–15 tissues/samples per individual) were performed on 88 seropositive, supposedly infected and euthanized individuals. Among them, 51 (58%) showed at least one positive culture, including 45 ibex with at least one Brucella isolation from a urogenital sample or a lymph node in the pelvic area (active infection in organs in the pelvic area). Among these 45 ibex, 26 (30% of the total number of necropsied animals) showed at least one positive culture for a urogenital organ and were considered as being at risk of shedding the bacteria at the time of capture. We observed significant heterogeneity between sex-and-age classes: seropositive females were most at risk to excrete Brucella before the age of 5 years, possibly corresponding to abortion during the first pregnancy following infection such as reported in the domestic ruminants. The high shedding potential observed in young females may have contributed to the self-sustained maintenance of infection in this population, whereas males are supposed to play a role of transmission between spatial units through venereal transmission during mating. This heterogeneity in the shedding potential of seropositive individuals should be considered in the future to better evaluate management scenarios in this system as well as in others.",2018 May 28,"['Lambert, Sébastien', 'Gilot-Fromont, Emmanuelle', 'Freycon, Pauline', 'Thébault, Anne', 'Game, Yvette', 'Toïgo, Carole', 'Petit, Elodie', 'Barthe, Marie-Noëlle', 'Reynaud, Gaël', 'Jaÿ, Maryne', 'Garin-Bastuji, Bruno', 'Ponsart, Claire', 'Hars, Jean', 'Rossi, Sophie']",Front Microbiol,,,True
7b9588d67ae1477f9d8534ee88d910be6349a78f,PMC,Evaluation of the EpiCore outbreak verification system,http://dx.doi.org/10.2471/BLT.17.207225,PMC5985427,29875517,CC BY,"OBJECTIVE: To describe a crowdsourced disease surveillance project (EpiCore) and evaluate its usefulness in obtaining information regarding potential disease outbreaks. METHODS: Volunteer human, animal and environmental health professionals from around the world were recruited to EpiCore and trained to provide early verification of health threat alerts in their geographical region via a secure, easy-to-use, online platform. Experts in the area of emerging infectious diseases sent requests for information on unverified health threats to these volunteers, who used local knowledge and expertise to respond to requests. Experts reviewed and summarized the responses and rapidly disseminated important information to the global health community through the existing event-based disease surveillance network, ProMED. FINDINGS: From March 2016 to September 2017, 2068 EpiCore volunteers from 142 countries were trained in methods of informal disease surveillance and use of the EpiCore online platform. These volunteers provided 790 individual responses to 759 requests for information addressing unverified health threats in 112 countries; 361 (45%) responses were considered to be useful. Most responses were received within hours of the requests. The responses led to 194 ProMED posts, of which 99 (51%) supported verification of an outbreak, were published on ProMED and sent to over 87 000 subscribers. CONCLUSION: There is widespread willingness among health professionals around the world to voluntarily assist efforts to verify and provide supporting information on unconfirmed health threats in their region. By linking this member network of health experts through a secure online reporting platform, EpiCore enables faster global outbreak detection and reporting.",2018 May 1,"['Lorthe, Taryn Silver', 'Pollack, Marjorie P', 'Lassmann, Britta', 'Brownstein, John S', 'Cohn, Emily', 'Divi, Nomita', 'Herrera-Guibert, Dionisio Jose', 'Olsen, Jennifer', 'Smolinski, Mark S', 'Madoff, Lawrence C']",Bull World Health Organ,,,True
d5ae540b13b8578550ddbcecdf9bc96ba1e1cf4c,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.18.010518,PMC5985429,29875512,CC BY,,2018 May 1,,Bull World Health Organ,,,False
d3c12db300a385a8668a0ee077a3b39c4e536c4e,PMC,Potential yellow fever epidemics in unexposed populations,http://dx.doi.org/10.2471/BLT.18.213298,PMC5985433,29875511,CC BY,,2018 May 1,"Gubler, Duane J",Bull World Health Organ,,,True
4e81674fc4eb37639e4710dcfdbaf442ac50052d,PMC,Epidemiological shift and geographical heterogeneity in the burden of leptospirosis in China,http://dx.doi.org/10.1186/s40249-018-0435-2,PMC5985562,29866175,CC BY,"BACKGROUND: Leptospirosis morbidity and mortality rates in China have decreased since the 2000s. Further analyses of the spatiotemporal and demographic changes occurring in the last decade and its implication on estimates of disease burden are required to inform intervention strategies. In this study, we quantified the epidemiological shift and geographical heterogeneity in the burden of leptospirosis during 2005–2015 in China. METHODS: We used reported leptospirosis case data from 1st January 2005 to 31st of December 2015 that routinely collected by the China Information System for Disease Control and Prevention (CISDCP) to analyze the epidemiological trend and estimate the burden in terms of disability-adjusted life-years (DALYs) over space, time, and demographical groups. RESULTS: A total of 7763 cases were reported during 2005–2015. Of which, 2403 (31%) cases were the laboratory-confirmed case. Since 2005, the notified incidence rate was gradually decreased (P < 0.05) and it was relatively stable during 2011–2015 (P > 0.05). During 2005–2015, we estimated a total of 10 313 DALYs were lost due to leptospirosis comprising a total of 1804 years-lived with disability (YLDs) and 8509 years-life lost (YLLs). Males had the highest burden of disease (7149 DALYs) compared to females (3164 DALYs). The highest burden estimate was attributed to younger individuals aged 10–19 years who lived in southern provinces of China. During 2005–2015, this age group contributed to approximately 3078 DALYs corresponding to 30% of the total DALYs lost in China. Yet, our analysis indicated a declining trend in burden estimates (P < 0.001) since 2005 and remained relatively low during 2011–2015. Low burden estimates have been identified in the endemic regions where infections principally distributed. Most of the changes in DALY estimates were driven by changes in YLLs. CONCLUSIONS: In the last 11-years, the burden estimates of leptospirosis have shown a declining trend across the country; however, leptospirosis should not be neglected as it remains an important zoonotic disease and potentially affecting the young and productive population in economically less-developed provinces in southern of China. In addition, while in the last five years the incidence has been reported at very low-level, this might not reflect the true incidence of leptospirosis. Strengthened surveillance in the endemic regions is, hence, substantially required to capture the actual prevalence to better control leptospirosis in China. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-018-0435-2) contains supplementary material, which is available to authorized users.",2018 May 18,"['Dhewantara, Pandji Wibawa', 'Mamun, Abdullah A.', 'Zhang, Wen-Yi', 'Yin, Wen-Wu', 'Ding, Fan', 'Guo, Danhuai', 'Hu, Wenbiao', 'Costa, Federico', 'Ko, Albert Icksang', 'Soares Magalhães, Ricardo J.']",Infect Dis Poverty,,,False
57f7587c21f25f1d1542599749ad28af764cf8e6,PMC,Epidemiological shift and geographical heterogeneity in the burden of leptospirosis in China,http://dx.doi.org/10.1186/s40249-018-0435-2,PMC5985562,29866175,CC BY,"BACKGROUND: Leptospirosis morbidity and mortality rates in China have decreased since the 2000s. Further analyses of the spatiotemporal and demographic changes occurring in the last decade and its implication on estimates of disease burden are required to inform intervention strategies. In this study, we quantified the epidemiological shift and geographical heterogeneity in the burden of leptospirosis during 2005–2015 in China. METHODS: We used reported leptospirosis case data from 1st January 2005 to 31st of December 2015 that routinely collected by the China Information System for Disease Control and Prevention (CISDCP) to analyze the epidemiological trend and estimate the burden in terms of disability-adjusted life-years (DALYs) over space, time, and demographical groups. RESULTS: A total of 7763 cases were reported during 2005–2015. Of which, 2403 (31%) cases were the laboratory-confirmed case. Since 2005, the notified incidence rate was gradually decreased (P < 0.05) and it was relatively stable during 2011–2015 (P > 0.05). During 2005–2015, we estimated a total of 10 313 DALYs were lost due to leptospirosis comprising a total of 1804 years-lived with disability (YLDs) and 8509 years-life lost (YLLs). Males had the highest burden of disease (7149 DALYs) compared to females (3164 DALYs). The highest burden estimate was attributed to younger individuals aged 10–19 years who lived in southern provinces of China. During 2005–2015, this age group contributed to approximately 3078 DALYs corresponding to 30% of the total DALYs lost in China. Yet, our analysis indicated a declining trend in burden estimates (P < 0.001) since 2005 and remained relatively low during 2011–2015. Low burden estimates have been identified in the endemic regions where infections principally distributed. Most of the changes in DALY estimates were driven by changes in YLLs. CONCLUSIONS: In the last 11-years, the burden estimates of leptospirosis have shown a declining trend across the country; however, leptospirosis should not be neglected as it remains an important zoonotic disease and potentially affecting the young and productive population in economically less-developed provinces in southern of China. In addition, while in the last five years the incidence has been reported at very low-level, this might not reflect the true incidence of leptospirosis. Strengthened surveillance in the endemic regions is, hence, substantially required to capture the actual prevalence to better control leptospirosis in China. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-018-0435-2) contains supplementary material, which is available to authorized users.",2018 May 18,"['Dhewantara, Pandji Wibawa', 'Mamun, Abdullah A.', 'Zhang, Wen-Yi', 'Yin, Wen-Wu', 'Ding, Fan', 'Guo, Danhuai', 'Hu, Wenbiao', 'Costa, Federico', 'Ko, Albert Icksang', 'Soares Magalhães, Ricardo J.']",Infect Dis Poverty,,,True
55db5d726c8d498815410266e74db0b59c40f0dc,PMC,Rapid detection and monitoring of human coronavirus infections,http://dx.doi.org/10.1016/j.nmni.2018.04.007,PMC5986163,29872531,CC BY,"Human coronaviruses (CoVs) are increasingly recognized as important respiratory pathogens associated with a broad range of clinical diseases. We sought to increase the insight into clinically relevant CoV infections by monitoring antigen concentrations in six confirmed CoV-positive patients using a newly developed assay for rapid detection of CoV OC43 infections. Antigen positivity lasted 3 to 6 days in secondary infections and 13 days in primary infection. CoV infections are clinically diverse, are common, and cannot be diagnosed from clinical symptoms alone.",2018 May 9,"['Bruning, A.H.L.', 'Aatola, H.', 'Toivola, H.', 'Ikonen, N.', 'Savolainen-Kopra, C.', 'Blomqvist, S.', 'Pajkrt, D.', 'Wolthers, K.C.', 'Koskinen, J.O.']",New Microbes New Infect,,,False
131bd567befa85f74a01b837c52d475cdd62aa38,PMC,Biological exacerbation clusters demonstrate asthma and chronic obstructive pulmonary disease overlap with distinct mediator and microbiome profiles,http://dx.doi.org/10.1016/j.jaci.2018.04.013,PMC5986707,29709671,CC BY,"BACKGROUND: Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous. OBJECTIVE: We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations. METHODS: Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center. Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation. Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators. Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters. RESULTS: The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology. Three exacerbation biologic clusters were identified. Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria. Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes. Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes. CONCLUSIONS: A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD. The sputum mediator and microbiome profiles were distinct between clusters.",2018 Jun,"['Ghebre, Michael A.', 'Pang, Pee Hwee', 'Diver, Sarah', 'Desai, Dhananjay', 'Bafadhel, Mona', 'Haldar, Koirobi', 'Kebadze, Tatiana', 'Cohen, Suzanne', 'Newbold, Paul', 'Rapley, Laura', 'Woods, Joanne', 'Rugman, Paul', 'Pavord, Ian D.', 'Johnston, Sebastian L.', 'Barer, Michael', 'May, Richard D.', 'Brightling, Christopher E.']",J Allergy Clin Immunol,,,False
961eb2f08c480672f033054cfce36910d0d37b7d,PMC,A Rapid and Specific Assay for the Detection of MERS-CoV,http://dx.doi.org/10.3389/fmicb.2018.01101,PMC5987675,29896174,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel human coronavirus that can cause human respiratory disease. The development of a detection method for this virus that can lead to rapid and accurate diagnosis would be significant. In this study, we established a nucleic acid visualization technique that combines the reverse transcription loop-mediated isothermal amplification technique and a vertical flow visualization strip (RT-LAMP-VF) to detect the N gene of MERS-CoV. The RT-LAMP-VF assay was performed in a constant temperature water bath for 30 min, and the result was visible by the naked eye within 5 min. The RT-LAMP-VF assay was capable of detecting 2 × 10(1) copies/μl of synthesized RNA transcript and 1 × 10(1) copies/μl of MERS-CoV RNA. The method exhibits no cross-reactivities with multiple CoVs including SARS-related (SARSr)-CoV, HKU4, HKU1, OC43 and 229E, and thus exhibits high specificity. Compared to the real-time RT-PCR (rRT-PCR) method recommended by the World Health Organization (WHO), the RT-LAMP-VF assay is easy to handle, does not require expensive equipment and can rapidly complete detection within 35 min.",2018 May 29,"['Huang, Pei', 'Wang, Hualei', 'Cao, Zengguo', 'Jin, Hongli', 'Chi, Hang', 'Zhao, Jincun', 'Yu, Beibei', 'Yan, Feihu', 'Hu, Xingxing', 'Wu, Fangfang', 'Jiao, Cuicui', 'Hou, Pengfei', 'Xu, Shengnan', 'Zhao, Yongkun', 'Feng, Na', 'Wang, Jianzhong', 'Sun, Weiyang', 'Wang, Tiecheng', 'Gao, Yuwei', 'Yang, Songtao', 'Xia, Xianzhu']",Front Microbiol,,,True
403e103aa496e1a37de56fde51173fdee75854fe,PMC,Aged Mice are More Resistant to Influenza Virus Infection due to Reduced Inflammation and Lung Pathology,http://dx.doi.org/10.14336/AD.2017.0701,PMC5988592,29896425,CC BY,"Immune responses are a double-edged sword. Effective and appropriate immune responses capable of controlling viral infection while also largely preserving tissue integrity, are critical for host survival. Too strong immune responses might result in immune pathology, while too weak immune responses might cause viral persistence. Physiologic ageing is accompanied with a decline in the normal functioning of the immune system, which is termed as ""immunosenescence"". We show that aged mice (16-19 months old) are more resistant to influenza A virus (IAV) infection than the young mice. Strong immune responses in the young mice after IAV infection result in faster clearance of virus, but also cause severe lung injury and higher mortality rate. While in the aged mice, the delayed and milder immune responses contribute to reduced pulmonary damage, and are still capable to clear the infection even with a slower kinetics, displaying a more resistant phenotype during IAV infection. Hence, our work demonstrates that moderate immune responses as a decline with ageing in the aged mice balance the immune pathology and viral clearance, might be beneficial for the host during certain circumstances. Our results provide important insight to our basic knowledge of immunosenescence and immune defenses to invading pathogens. Further, our results indicate that age factors should be considered when investigating the vaccination and therapeutic strategies for severe IAV infection.",2018 Jun 1,"['Lu, Jiao', 'Duan, Xuefeng', 'Zhao, Wenming', 'Wang, Jing', 'Wang, Haoyu', 'Zhou, Kai', 'Fang, Min']",Aging Dis,,,True
f6d97909fada387260787c6961eb1c4c36dac9d1,PMC,The emergence of novel sparrow deltacoronaviruses in the United States more closely related to porcine deltacoronaviruses than sparrow deltacoronavirus HKU17,http://dx.doi.org/10.1038/s41426-018-0108-z,PMC5988828,29872066,CC BY,,2018 Jun 6,"['Chen, Qi', 'Wang, Leyi', 'Yang, Chenghuai', 'Zheng, Ying', 'Gauger, Phillip C.', 'Anderson, Tavis', 'Harmon, Karen M.', 'Zhang, Jianqiang', 'Yoon, Kyoung-Jin', 'Main, Rodger G.', 'Li, Ganwu']",Emerg Microbes Infect,,,True
5e545b25250d9239c3096fa6925fad84c88199cf,PMC,Emergence and Evolution of Novel Reassortant Influenza A Viruses in Canines in Southern China,http://dx.doi.org/10.1128/mBio.00909-18,PMC5989073,29871917,CC BY,"The capacity of influenza A viruses (IAVs) to host jump from animal reservoir species to humans presents an ongoing pandemic threat. Birds and swine are considered major reservoirs of viral genetic diversity, whereas equines and canines have historically been restricted to one or two stable IAV lineages with no transmission to humans. Here, by sequencing the complete genomes of 16 IAVs obtained from canines in southern China (Guangxi Zhuang Autonomous Region [Guangxi]) in 2013 to 2015, we demonstrate that the evolution of canine influenza viruses (CIVs) in Asian dogs is increasingly complex, presenting a potential threat to humans. First, two reassortant H1N1 virus genotypes were introduced independently from swine into canines in Guangxi, including one genotype associated with a zoonotic infection. The genomes contain segments from three lineages that circulate in swine in China: North American triple reassortant H3N2, Eurasian avian-like H1N1, and pandemic H1N1. Furthermore, the swine-origin H1N1 viruses have transmitted onward in canines and reassorted with the CIV-H3N2 viruses that circulate endemically in Asian dogs, producing three novel reassortant CIV genotypes (H1N1r, H1N2r, and H3N2r [r stands for reassortant]). CIVs from this study were collected primarily from pet dogs presenting with respiratory symptoms at veterinary clinics, but dogs in Guangxi are also raised for meat, and street dogs roam freely, creating a more complex ecosystem for CIV transmission. Further surveillance is greatly needed to understand the full genetic diversity of CIV in southern China, the nature of viral emergence and persistence in the region’s diverse canine populations, and the zoonotic risk as the viruses continue to evolve.",2018 Jun 5,"['Chen, Ying', 'Trovão, Nídia S.', 'Wang, Guojun', 'Zhao, Weifeng', 'He, Ping', 'Zhou, Huabo', 'Mo, Yanning', 'Wei, Zuzhang', 'Ouyang, Kang', 'Huang, Weijian', 'García-Sastre, Adolfo', 'Nelson, Martha I.']",mBio,,,True
01311c00531433205112bb49c80432dd9299576c,PMC,Emergence and Evolution of Novel Reassortant Influenza A Viruses in Canines in Southern China,http://dx.doi.org/10.1128/mBio.00909-18,PMC5989073,29871917,CC BY,"The capacity of influenza A viruses (IAVs) to host jump from animal reservoir species to humans presents an ongoing pandemic threat. Birds and swine are considered major reservoirs of viral genetic diversity, whereas equines and canines have historically been restricted to one or two stable IAV lineages with no transmission to humans. Here, by sequencing the complete genomes of 16 IAVs obtained from canines in southern China (Guangxi Zhuang Autonomous Region [Guangxi]) in 2013 to 2015, we demonstrate that the evolution of canine influenza viruses (CIVs) in Asian dogs is increasingly complex, presenting a potential threat to humans. First, two reassortant H1N1 virus genotypes were introduced independently from swine into canines in Guangxi, including one genotype associated with a zoonotic infection. The genomes contain segments from three lineages that circulate in swine in China: North American triple reassortant H3N2, Eurasian avian-like H1N1, and pandemic H1N1. Furthermore, the swine-origin H1N1 viruses have transmitted onward in canines and reassorted with the CIV-H3N2 viruses that circulate endemically in Asian dogs, producing three novel reassortant CIV genotypes (H1N1r, H1N2r, and H3N2r [r stands for reassortant]). CIVs from this study were collected primarily from pet dogs presenting with respiratory symptoms at veterinary clinics, but dogs in Guangxi are also raised for meat, and street dogs roam freely, creating a more complex ecosystem for CIV transmission. Further surveillance is greatly needed to understand the full genetic diversity of CIV in southern China, the nature of viral emergence and persistence in the region’s diverse canine populations, and the zoonotic risk as the viruses continue to evolve.",2018 Jun 5,"['Chen, Ying', 'Trovão, Nídia S.', 'Wang, Guojun', 'Zhao, Weifeng', 'He, Ping', 'Zhou, Huabo', 'Mo, Yanning', 'Wei, Zuzhang', 'Ouyang, Kang', 'Huang, Weijian', 'García-Sastre, Adolfo', 'Nelson, Martha I.']",mBio,,,False
6a52bb71cd3c642c0a38b71cdc868cc345a10632,PMC,Emergence and Evolution of Novel Reassortant Influenza A Viruses in Canines in Southern China,http://dx.doi.org/10.1128/mBio.00909-18,PMC5989073,29871917,CC BY,"The capacity of influenza A viruses (IAVs) to host jump from animal reservoir species to humans presents an ongoing pandemic threat. Birds and swine are considered major reservoirs of viral genetic diversity, whereas equines and canines have historically been restricted to one or two stable IAV lineages with no transmission to humans. Here, by sequencing the complete genomes of 16 IAVs obtained from canines in southern China (Guangxi Zhuang Autonomous Region [Guangxi]) in 2013 to 2015, we demonstrate that the evolution of canine influenza viruses (CIVs) in Asian dogs is increasingly complex, presenting a potential threat to humans. First, two reassortant H1N1 virus genotypes were introduced independently from swine into canines in Guangxi, including one genotype associated with a zoonotic infection. The genomes contain segments from three lineages that circulate in swine in China: North American triple reassortant H3N2, Eurasian avian-like H1N1, and pandemic H1N1. Furthermore, the swine-origin H1N1 viruses have transmitted onward in canines and reassorted with the CIV-H3N2 viruses that circulate endemically in Asian dogs, producing three novel reassortant CIV genotypes (H1N1r, H1N2r, and H3N2r [r stands for reassortant]). CIVs from this study were collected primarily from pet dogs presenting with respiratory symptoms at veterinary clinics, but dogs in Guangxi are also raised for meat, and street dogs roam freely, creating a more complex ecosystem for CIV transmission. Further surveillance is greatly needed to understand the full genetic diversity of CIV in southern China, the nature of viral emergence and persistence in the region’s diverse canine populations, and the zoonotic risk as the viruses continue to evolve.",2018 Jun 5,"['Chen, Ying', 'Trovão, Nídia S.', 'Wang, Guojun', 'Zhao, Weifeng', 'He, Ping', 'Zhou, Huabo', 'Mo, Yanning', 'Wei, Zuzhang', 'Ouyang, Kang', 'Huang, Weijian', 'García-Sastre, Adolfo', 'Nelson, Martha I.']",mBio,,,False
c0bca5c3841fd7abdbb4d3d299dc6de427a7ef71,PMC,Emergence and Evolution of Novel Reassortant Influenza A Viruses in Canines in Southern China,http://dx.doi.org/10.1128/mBio.00909-18,PMC5989073,29871917,CC BY,"The capacity of influenza A viruses (IAVs) to host jump from animal reservoir species to humans presents an ongoing pandemic threat. Birds and swine are considered major reservoirs of viral genetic diversity, whereas equines and canines have historically been restricted to one or two stable IAV lineages with no transmission to humans. Here, by sequencing the complete genomes of 16 IAVs obtained from canines in southern China (Guangxi Zhuang Autonomous Region [Guangxi]) in 2013 to 2015, we demonstrate that the evolution of canine influenza viruses (CIVs) in Asian dogs is increasingly complex, presenting a potential threat to humans. First, two reassortant H1N1 virus genotypes were introduced independently from swine into canines in Guangxi, including one genotype associated with a zoonotic infection. The genomes contain segments from three lineages that circulate in swine in China: North American triple reassortant H3N2, Eurasian avian-like H1N1, and pandemic H1N1. Furthermore, the swine-origin H1N1 viruses have transmitted onward in canines and reassorted with the CIV-H3N2 viruses that circulate endemically in Asian dogs, producing three novel reassortant CIV genotypes (H1N1r, H1N2r, and H3N2r [r stands for reassortant]). CIVs from this study were collected primarily from pet dogs presenting with respiratory symptoms at veterinary clinics, but dogs in Guangxi are also raised for meat, and street dogs roam freely, creating a more complex ecosystem for CIV transmission. Further surveillance is greatly needed to understand the full genetic diversity of CIV in southern China, the nature of viral emergence and persistence in the region’s diverse canine populations, and the zoonotic risk as the viruses continue to evolve.",2018 Jun 5,"['Chen, Ying', 'Trovão, Nídia S.', 'Wang, Guojun', 'Zhao, Weifeng', 'He, Ping', 'Zhou, Huabo', 'Mo, Yanning', 'Wei, Zuzhang', 'Ouyang, Kang', 'Huang, Weijian', 'García-Sastre, Adolfo', 'Nelson, Martha I.']",mBio,,,False
9d4b12aca4e76ed4036444fbfbc96170578ff17e,PMC,Emergence and Evolution of Novel Reassortant Influenza A Viruses in Canines in Southern China,http://dx.doi.org/10.1128/mBio.00909-18,PMC5989073,29871917,CC BY,"The capacity of influenza A viruses (IAVs) to host jump from animal reservoir species to humans presents an ongoing pandemic threat. Birds and swine are considered major reservoirs of viral genetic diversity, whereas equines and canines have historically been restricted to one or two stable IAV lineages with no transmission to humans. Here, by sequencing the complete genomes of 16 IAVs obtained from canines in southern China (Guangxi Zhuang Autonomous Region [Guangxi]) in 2013 to 2015, we demonstrate that the evolution of canine influenza viruses (CIVs) in Asian dogs is increasingly complex, presenting a potential threat to humans. First, two reassortant H1N1 virus genotypes were introduced independently from swine into canines in Guangxi, including one genotype associated with a zoonotic infection. The genomes contain segments from three lineages that circulate in swine in China: North American triple reassortant H3N2, Eurasian avian-like H1N1, and pandemic H1N1. Furthermore, the swine-origin H1N1 viruses have transmitted onward in canines and reassorted with the CIV-H3N2 viruses that circulate endemically in Asian dogs, producing three novel reassortant CIV genotypes (H1N1r, H1N2r, and H3N2r [r stands for reassortant]). CIVs from this study were collected primarily from pet dogs presenting with respiratory symptoms at veterinary clinics, but dogs in Guangxi are also raised for meat, and street dogs roam freely, creating a more complex ecosystem for CIV transmission. Further surveillance is greatly needed to understand the full genetic diversity of CIV in southern China, the nature of viral emergence and persistence in the region’s diverse canine populations, and the zoonotic risk as the viruses continue to evolve.",2018 Jun 5,"['Chen, Ying', 'Trovão, Nídia S.', 'Wang, Guojun', 'Zhao, Weifeng', 'He, Ping', 'Zhou, Huabo', 'Mo, Yanning', 'Wei, Zuzhang', 'Ouyang, Kang', 'Huang, Weijian', 'García-Sastre, Adolfo', 'Nelson, Martha I.']",mBio,,,False
dddf8068143a0d8883230531fa95d7c7d339929c,PMC,Emergence and Evolution of Novel Reassortant Influenza A Viruses in Canines in Southern China,http://dx.doi.org/10.1128/mBio.00909-18,PMC5989073,29871917,CC BY,"The capacity of influenza A viruses (IAVs) to host jump from animal reservoir species to humans presents an ongoing pandemic threat. Birds and swine are considered major reservoirs of viral genetic diversity, whereas equines and canines have historically been restricted to one or two stable IAV lineages with no transmission to humans. Here, by sequencing the complete genomes of 16 IAVs obtained from canines in southern China (Guangxi Zhuang Autonomous Region [Guangxi]) in 2013 to 2015, we demonstrate that the evolution of canine influenza viruses (CIVs) in Asian dogs is increasingly complex, presenting a potential threat to humans. First, two reassortant H1N1 virus genotypes were introduced independently from swine into canines in Guangxi, including one genotype associated with a zoonotic infection. The genomes contain segments from three lineages that circulate in swine in China: North American triple reassortant H3N2, Eurasian avian-like H1N1, and pandemic H1N1. Furthermore, the swine-origin H1N1 viruses have transmitted onward in canines and reassorted with the CIV-H3N2 viruses that circulate endemically in Asian dogs, producing three novel reassortant CIV genotypes (H1N1r, H1N2r, and H3N2r [r stands for reassortant]). CIVs from this study were collected primarily from pet dogs presenting with respiratory symptoms at veterinary clinics, but dogs in Guangxi are also raised for meat, and street dogs roam freely, creating a more complex ecosystem for CIV transmission. Further surveillance is greatly needed to understand the full genetic diversity of CIV in southern China, the nature of viral emergence and persistence in the region’s diverse canine populations, and the zoonotic risk as the viruses continue to evolve.",2018 Jun 5,"['Chen, Ying', 'Trovão, Nídia S.', 'Wang, Guojun', 'Zhao, Weifeng', 'He, Ping', 'Zhou, Huabo', 'Mo, Yanning', 'Wei, Zuzhang', 'Ouyang, Kang', 'Huang, Weijian', 'García-Sastre, Adolfo', 'Nelson, Martha I.']",mBio,,,False
427b6f00b5d8c62a878fc84e4870cce9a7f4cde9,PMC,Emergence and Evolution of Novel Reassortant Influenza A Viruses in Canines in Southern China,http://dx.doi.org/10.1128/mBio.00909-18,PMC5989073,29871917,CC BY,"The capacity of influenza A viruses (IAVs) to host jump from animal reservoir species to humans presents an ongoing pandemic threat. Birds and swine are considered major reservoirs of viral genetic diversity, whereas equines and canines have historically been restricted to one or two stable IAV lineages with no transmission to humans. Here, by sequencing the complete genomes of 16 IAVs obtained from canines in southern China (Guangxi Zhuang Autonomous Region [Guangxi]) in 2013 to 2015, we demonstrate that the evolution of canine influenza viruses (CIVs) in Asian dogs is increasingly complex, presenting a potential threat to humans. First, two reassortant H1N1 virus genotypes were introduced independently from swine into canines in Guangxi, including one genotype associated with a zoonotic infection. The genomes contain segments from three lineages that circulate in swine in China: North American triple reassortant H3N2, Eurasian avian-like H1N1, and pandemic H1N1. Furthermore, the swine-origin H1N1 viruses have transmitted onward in canines and reassorted with the CIV-H3N2 viruses that circulate endemically in Asian dogs, producing three novel reassortant CIV genotypes (H1N1r, H1N2r, and H3N2r [r stands for reassortant]). CIVs from this study were collected primarily from pet dogs presenting with respiratory symptoms at veterinary clinics, but dogs in Guangxi are also raised for meat, and street dogs roam freely, creating a more complex ecosystem for CIV transmission. Further surveillance is greatly needed to understand the full genetic diversity of CIV in southern China, the nature of viral emergence and persistence in the region’s diverse canine populations, and the zoonotic risk as the viruses continue to evolve.",2018 Jun 5,"['Chen, Ying', 'Trovão, Nídia S.', 'Wang, Guojun', 'Zhao, Weifeng', 'He, Ping', 'Zhou, Huabo', 'Mo, Yanning', 'Wei, Zuzhang', 'Ouyang, Kang', 'Huang, Weijian', 'García-Sastre, Adolfo', 'Nelson, Martha I.']",mBio,,,False
cbca4377d54d06b3758597c0e562f3cc39427810,PMC,Metagenomics detection and characterisation of viruses in faecal samples from Australian wild birds,http://dx.doi.org/10.1038/s41598-018-26851-1,PMC5989203,29875375,CC BY,"We present an optimised metagenomics method for detection and characterisation of all virus types including single and double stranded DNA/RNA and enveloped and non-enveloped viruses. Initial evaluation included both spiked and non-spiked bird faecal samples as well as non-spiked human faecal samples. From the non-spiked bird samples (Australian Muscovy duck and Pacific black ducks) we detected 21 viruses, and we also present a summary of a few viruses detected in human faecal samples. We then present a detailed analysis of selected virus sequences in the avian samples that were somewhat similar to known viruses, and had good quality (Q20 or higher) and quantity of next-generation sequencing reads, and was of interest from a virological point of view, for example, avian coronavirus and avian paramyxovirus 6. Some of these viruses were closely related to known viruses while others were more distantly related with 70% or less identity to currently known/sequenced viruses. Besides detecting viruses, the technique also allowed the characterisation of host mitochondrial DNA present and thus identifying host species, while ribosomal RNA sequences provided insight into the “ribosomal activity microbiome”; of gut parasites; and of food eaten such as plants or insects, which we correlated to non-avian host associated viruses.",2018 Jun 6,"['Vibin, Jessy', 'Chamings, Anthony', 'Collier, Fiona', 'Klaassen, Marcel', 'Nelson, Tiffanie M.', 'Alexandersen, Soren']",Sci Rep,,,True
e5a309be751ae9e2575c3e35edd7f37fa0e99b3d,PMC,Metagenomics detection and characterisation of viruses in faecal samples from Australian wild birds,http://dx.doi.org/10.1038/s41598-018-26851-1,PMC5989203,29875375,CC BY,"We present an optimised metagenomics method for detection and characterisation of all virus types including single and double stranded DNA/RNA and enveloped and non-enveloped viruses. Initial evaluation included both spiked and non-spiked bird faecal samples as well as non-spiked human faecal samples. From the non-spiked bird samples (Australian Muscovy duck and Pacific black ducks) we detected 21 viruses, and we also present a summary of a few viruses detected in human faecal samples. We then present a detailed analysis of selected virus sequences in the avian samples that were somewhat similar to known viruses, and had good quality (Q20 or higher) and quantity of next-generation sequencing reads, and was of interest from a virological point of view, for example, avian coronavirus and avian paramyxovirus 6. Some of these viruses were closely related to known viruses while others were more distantly related with 70% or less identity to currently known/sequenced viruses. Besides detecting viruses, the technique also allowed the characterisation of host mitochondrial DNA present and thus identifying host species, while ribosomal RNA sequences provided insight into the “ribosomal activity microbiome”; of gut parasites; and of food eaten such as plants or insects, which we correlated to non-avian host associated viruses.",2018 Jun 6,"['Vibin, Jessy', 'Chamings, Anthony', 'Collier, Fiona', 'Klaassen, Marcel', 'Nelson, Tiffanie M.', 'Alexandersen, Soren']",Sci Rep,,,True
25ad50eb42a7f0addf4bc0ce7a0f8f1a0f991616,PMC,"Prophylactic efficacy of orally administered Bacillus poly-γ-glutamic acid, a non-LPS TLR4 ligand, against norovirus infection in mice",http://dx.doi.org/10.1038/s41598-018-26935-y,PMC5989232,29875467,CC BY,"Poly-gamma-glutamic acid (γ-PGA), an extracellular biopolymer produced by Bacillus sp., is a non-canonical toll-like receptor 4 (TLR4) agonist. Here we show its antiviral efficacy against noroviruses. γ-PGA with a molecular mass of 2,000-kDa limited murine norovirus (MNV) replication in the macrophage cell line RAW264.7 by inducing interferon (IFN)-β and conferred resistance to viral infection-induced cell death. Additionally, γ-PGA interfered with viral entry into cells. The potent antiviral state mounted by γ-PGA was not attributed to the upregulation of TLR4 or TLR3, a sensor known to recognize norovirus RNA. γ-PGA sensing by TLR4 required the two TLR4-associated accessory factors MD2 and CD14. In ex vivo cultures of mouse ileum, γ-PGA selectively increased the expression of IFN-β in villi. In contrast, IFN-β induction was negligible in the ileal Peyer’s patches (PPs) where its expression was primarily induced by the replication of MNV. Oral administration of γ-PGA, which increased serum IFN-β levels without inducing proinflammatory cytokines, reduced MNV loads in the ileum with PPs and mesenteric lymph nodes in mice. Our results disclose a γ-PGA-mediated non-conventional TLR4 signaling in the ileum, highlighting the potential use of γ-PGA as a prophylactic antiviral agent against noroviruses.",2018 Jun 6,"['Lee, Wooseong', 'Kim, Minwoo', 'Lee, Seung-Hoon', 'Jung, Hae-Gwang', 'Oh, Jong-Won']",Sci Rep,,,False
0715fd9f3fec7a2b86f3344c3c3a56611bcea4aa,PMC,"Prophylactic efficacy of orally administered Bacillus poly-γ-glutamic acid, a non-LPS TLR4 ligand, against norovirus infection in mice",http://dx.doi.org/10.1038/s41598-018-26935-y,PMC5989232,29875467,CC BY,"Poly-gamma-glutamic acid (γ-PGA), an extracellular biopolymer produced by Bacillus sp., is a non-canonical toll-like receptor 4 (TLR4) agonist. Here we show its antiviral efficacy against noroviruses. γ-PGA with a molecular mass of 2,000-kDa limited murine norovirus (MNV) replication in the macrophage cell line RAW264.7 by inducing interferon (IFN)-β and conferred resistance to viral infection-induced cell death. Additionally, γ-PGA interfered with viral entry into cells. The potent antiviral state mounted by γ-PGA was not attributed to the upregulation of TLR4 or TLR3, a sensor known to recognize norovirus RNA. γ-PGA sensing by TLR4 required the two TLR4-associated accessory factors MD2 and CD14. In ex vivo cultures of mouse ileum, γ-PGA selectively increased the expression of IFN-β in villi. In contrast, IFN-β induction was negligible in the ileal Peyer’s patches (PPs) where its expression was primarily induced by the replication of MNV. Oral administration of γ-PGA, which increased serum IFN-β levels without inducing proinflammatory cytokines, reduced MNV loads in the ileum with PPs and mesenteric lymph nodes in mice. Our results disclose a γ-PGA-mediated non-conventional TLR4 signaling in the ileum, highlighting the potential use of γ-PGA as a prophylactic antiviral agent against noroviruses.",2018 Jun 6,"['Lee, Wooseong', 'Kim, Minwoo', 'Lee, Seung-Hoon', 'Jung, Hae-Gwang', 'Oh, Jong-Won']",Sci Rep,,,True
02aabb0b8eb8a3f3692e162442bbed19c5f915b6,PMC,"Synchronized shift of oral, faecal and urinary microbiotas in bats and natural infection dynamics during seasonal reproduction",http://dx.doi.org/10.1098/rsos.180041,PMC5990816,29892443,CC BY,"Seasonal reproduction is a period of extreme physiological and behavioural changes, yet we know little about how it may affect host microbial communities (i.e. microbiota) and pathogen transmission. Here, we investigated shifts of the bacterial microbiota in saliva, urine and faeces during the seasonal reproduction of bats in South Africa, and test for an interaction in shedding patterns of both bacterial (Leptospira) and viral (adeno- and herpesviruses) agents. Based on a comparative approach in two cave-dwelling bat species and high-throughput sequencing of the 16S rRNA gene, we demonstrated a clear signature in microbiota changes over the reproduction season, consistent across the multiple body habitats investigated, and associated with the sex, age and reproductive condition of bats. We observed in parallel highly dynamic shedding patterns for both bacteria and viruses, but did not find a significant association between viral shedding and bacterial microbiota composition. Indeed, only Leptospira shedding was associated with alterations in both the diversity and composition of the urinary microbiota. These results illustrate how seasonal reproduction in bats substantially affects microbiota composition and infection dynamics, and have broad implications for the understanding of disease ecology in important reservoir hosts, such as bats.",2018 May 2,"['Dietrich, Muriel', 'Kearney, Teresa', 'Seamark, Ernest C. J.', 'Paweska, Janusz T.', 'Markotter, Wanda']",R Soc Open Sci,,,True
3633ffe6e8c7f4af342b1a5d23821169f7f9e1b2,PMC,"Synchronized shift of oral, faecal and urinary microbiotas in bats and natural infection dynamics during seasonal reproduction",http://dx.doi.org/10.1098/rsos.180041,PMC5990816,29892443,CC BY,"Seasonal reproduction is a period of extreme physiological and behavioural changes, yet we know little about how it may affect host microbial communities (i.e. microbiota) and pathogen transmission. Here, we investigated shifts of the bacterial microbiota in saliva, urine and faeces during the seasonal reproduction of bats in South Africa, and test for an interaction in shedding patterns of both bacterial (Leptospira) and viral (adeno- and herpesviruses) agents. Based on a comparative approach in two cave-dwelling bat species and high-throughput sequencing of the 16S rRNA gene, we demonstrated a clear signature in microbiota changes over the reproduction season, consistent across the multiple body habitats investigated, and associated with the sex, age and reproductive condition of bats. We observed in parallel highly dynamic shedding patterns for both bacteria and viruses, but did not find a significant association between viral shedding and bacterial microbiota composition. Indeed, only Leptospira shedding was associated with alterations in both the diversity and composition of the urinary microbiota. These results illustrate how seasonal reproduction in bats substantially affects microbiota composition and infection dynamics, and have broad implications for the understanding of disease ecology in important reservoir hosts, such as bats.",2018 May 2,"['Dietrich, Muriel', 'Kearney, Teresa', 'Seamark, Ernest C. J.', 'Paweska, Janusz T.', 'Markotter, Wanda']",R Soc Open Sci,,,True
a8c1235bde8c7b6c2be395f062d100de29e658b1,PMC,Zika virus-induced acute myelitis and motor deficits in adult interferon αβ/γ receptor knockout mice,http://dx.doi.org/10.1007/s13365-017-0595-z,PMC5992253,29476408,CC BY,"Zika virus (ZIKV) has received widespread attention because of its effect on the developing fetus. It is becoming apparent, however, that severe neurological sequelae, such as Guillian-Barrë syndrome (GBS), myelitis, encephalitis, and seizures can occur after infection of adults. This study demonstrates that a contemporary strain of ZIKV can widely infect astrocytes and neurons in the brain and spinal cord of adult, interferon α/β receptor knockout mice (AG129 strain) and cause progressive hindlimb paralysis, as well as severe seizure-like activity during the acute phase of disease. The severity of hindlimb motor deficits correlated with increased numbers of ZIKV-infected lumbosacral spinal motor neurons and decreased numbers of spinal motor neurons. Electrophysiological compound muscle action potential (CMAP) amplitudes in response to stimulation of the lumbosacral spinal cord were reduced when obvious motor deficits were present. ZIKV immunoreactivity was high, intense, and obvious in tissue sections of the brain and spinal cord. Infection in the brain and spinal cord was also associated with astrogliosis as well as T cell and neutrophil infiltration. CMAP and histological analysis indicated that peripheral nerve and muscle functions were intact. Consequently, motor deficits in these circumstances appear to be primarily due to myelitis and possibly encephalitis as opposed to a peripheral neuropathy or a GBS-like syndrome. Thus, acute ZIKV infection of adult AG129 mice may be a useful model for ZIKV-induced myelitis, encephalitis, and seizure activity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13365-017-0595-z) contains supplementary material, which is available to authorized users.",2018 Feb 23,"['Zukor, Katherine', 'Wang, Hong', 'Siddharthan, Venkatraman', 'Julander, Justin G.', 'Morrey, John D.']",J Neurovirol,,,True
13bc396fab607d24e0dfd5b38704463d13a85c08,PMC,Changing Priorities in Vaccinology: Antibiotic Resistance Moving to the Top,http://dx.doi.org/10.3389/fimmu.2018.01068,PMC5992407,29910799,CC BY,"Antimicrobial resistance (AMR) is currently the most alarming issue for human health. AMR already causes 700,000 deaths/year. It is estimated that 10 million deaths due to AMR will occur every year after 2050. This equals the number of people dying of cancer every year in present times. International institutions such as G20, World Bank, World Health Organization (WHO), UN General Assembly, European Union, and the UK and USA governments are calling for new antibiotics. To underline this emergency, a list of antibiotic-resistant “priority pathogens” has been published by WHO. It contains 12 families of bacteria that represent the greatest danger for human health. Resistance to multiple antibiotics is particularly relevant for the Gram-negative bacteria present in the list. The ability of these bacteria to develop mechanisms to resist treatment could be transmitted with genetic material, allowing other bacteria to become drug resistant. Although the search for new antimicrobial drugs remains a top priority, the pipeline for new antibiotics is not promising, and alternative solutions are needed. A possible answer to AMR is vaccination. In fact, while antibiotic resistance emerges rapidly, vaccines can lead to a much longer lasting control of infections. New technologies, such as the high-throughput cloning of human B cells from convalescent or vaccinated people, allow for finding new protective antigens (Ags) that could not be identified with conventional technologies. Antibodies produced by convalescent B cell clones can be screened for their ability to bind, block, and kill bacteria, using novel high-throughput microscopy platforms that rapidly capture digital images, or by conventional technologies such as bactericidal, opsono-phagocytosis and FACS assays. Selected antibodies expressed by recombinant DNA techniques can be used for passive immunization in animal models and tested for protection. Antibodies providing the best protection can be employed to identify new Ags and then used for generating highly specific recombinant Fab fragments. Co-crystallization of Ags bound to Fab fragments will allow us to determine the structure and characteristics of new Ags. This structure-based Ag design will bring to a new generation of vaccines able to target previously elusive infections, thereby offering an effective solution to the problem of AMR.",2018 May 30,"['Tagliabue, Aldo', 'Rappuoli, Rino']",Front Immunol,,,True
d5c3ab7d56a6d04ce4feb57a5dd9d0059abca0a7,PMC,"Global prevalence and distribution of coinfection of malaria, dengue and chikungunya: a systematic review",http://dx.doi.org/10.1186/s12889-018-5626-z,PMC5992662,29879935,CC BY,"BACKGROUND: Malaria, Dengue and Chikungunya are vector borne diseases with shared endemic profiles and symptoms. Coinfections with any of these diseases could have fatal outcomes if left undiagnosed. Understanding the prevalence and distribution of coinfections is necessary to improve diagnosis and designing therapeutic interventions. METHODS: We have carried out a systematic search of the published literature based on PRISMA guidelines to identify cases of Malaria, Dengue and Chikungunya coinfections. We systematically reviewed the literature to identify eligible studies and extracted data regarding cases of coinfection from cross sectional studies, case reports, retrospective studies, prospective observational studies and surveillance reports. RESULTS: Care full screening resulted in 104 publications that met the eligibility criteria and reported Malaria/Dengue, Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections. These coinfections were spread over six geographical locations and 42 different countries and are reported more frequently in the last 15 years possibly due to expanding epidemiology of Dengue and Chikungunya. Few of these reports have also analysed distinguishing features of coinfections. Malaria/Dengue coinfections were the most common coinfection followed by Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections. P. falciparum and P. vivax were the commonest species found in cases of malaria coinfections and Dengue serotype-4 commonest serotype in cases of dengue coinfections. Most studies were reported from India. Nigeria and India were the only two countries from where all possible combinations of coinfections were reported. CONCLUSION: We have comprehensively reviewed the literature associated with cases of coinfections of three important vector borne diseases to present a clear picture of their prevalence and distribution across the globe. The frequency of coinfections presented in the study suggests proper diagnosis, surveillance and management of cases of coinfection to avoid poor prognosis of the underlying etiology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-018-5626-z) contains supplementary material, which is available to authorized users.",2018 Jun 8,"['Salam, Nasir', 'Mustafa, Shoeb', 'Hafiz, Abdul', 'Chaudhary, Anis Ahmad', 'Deeba, Farah', 'Parveen, Shama']",BMC Public Health,,,True
13660e28e811f68a1ddcca218db0b67b44632df3,PMC,Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations,http://dx.doi.org/10.1038/s41467-018-04574-1,PMC5993715,29884817,CC BY,"Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms. Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections. Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations. Exogenous interferon-β reverses these effects. FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways. Mice deficient in the type I interferon-α/β receptor (IFNAR1(−/−)) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection. This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production. Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.",2018 Jun 8,"['Singanayagam, Aran', 'Glanville, Nicholas', 'Girkin, Jason L.', 'Ching, Yee Man', 'Marcellini, Andrea', 'Porter, James D.', 'Toussaint, Marie', 'Walton, Ross P.', 'Finney, Lydia J.', 'Aniscenko, Julia', 'Zhu, Jie', 'Trujillo-Torralbo, Maria-Belen', 'Calderazzo, Maria Adelaide', 'Grainge, Chris', 'Loo, Su-Ling', 'Veerati, Punnam Chander', 'Pathinayake, Prabuddha S.', 'Nichol, Kristy S.', 'Reid, Andrew T.', 'James, Phillip L.', 'Solari, Roberto', 'Wark, Peter A. B.', 'Knight, Darryl A.', 'Moffatt, Miriam F.', 'Cookson, William O.', 'Edwards, Michael R.', 'Mallia, Patrick', 'Bartlett, Nathan W.', 'Johnston, Sebastian L.']",Nat Commun,,,False
f601b810174ec3f6056d0806959c06a2b211f3ca,PMC,Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations,http://dx.doi.org/10.1038/s41467-018-04574-1,PMC5993715,29884817,CC BY,"Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms. Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections. Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations. Exogenous interferon-β reverses these effects. FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways. Mice deficient in the type I interferon-α/β receptor (IFNAR1(−/−)) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection. This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production. Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.",2018 Jun 8,"['Singanayagam, Aran', 'Glanville, Nicholas', 'Girkin, Jason L.', 'Ching, Yee Man', 'Marcellini, Andrea', 'Porter, James D.', 'Toussaint, Marie', 'Walton, Ross P.', 'Finney, Lydia J.', 'Aniscenko, Julia', 'Zhu, Jie', 'Trujillo-Torralbo, Maria-Belen', 'Calderazzo, Maria Adelaide', 'Grainge, Chris', 'Loo, Su-Ling', 'Veerati, Punnam Chander', 'Pathinayake, Prabuddha S.', 'Nichol, Kristy S.', 'Reid, Andrew T.', 'James, Phillip L.', 'Solari, Roberto', 'Wark, Peter A. B.', 'Knight, Darryl A.', 'Moffatt, Miriam F.', 'Cookson, William O.', 'Edwards, Michael R.', 'Mallia, Patrick', 'Bartlett, Nathan W.', 'Johnston, Sebastian L.']",Nat Commun,,,True
bce65fb977ab27efae9992d88884173851877570,PMC,A Review on Emerging and Reemerging of Infectious Diseases in Jordan: The Aftermath of the Syrian Crises,http://dx.doi.org/10.1155/2018/8679174,PMC5994294,29977415,CC BY,"The review aims to examine the emergence and reemergence of infectious diseases in Jordan, in parallel with the Syrian refugee crisis. Qualitative approach has been adopted for systematically examining the outcomes of the Syrian crisis, which resulted in emerging and reemerging infectious diseases. It has adhered that infectious diseases, including measles, tuberculosis, and cutaneous leishmaniasis, have hazardous effects on Syrian refugees along with the local population in Jordan. The threat of major infectious diseases is higher and alarming in Jordan. National health policies should be implemented to adhere the influence of infectious diseases as well as to reduce the extent of infectious diseases in Jordan. In the 21st century, Syrian conflict can be deliberated as one of the biggest humanitarian disasters. In this multifaceted emergency with devastating requirements and limitations, it has been found essential for dominant medical healthcare providers to develop medical strategies that are based on comprehensive understanding of the concerned context and the main medical requirements and susceptible groups.",2018 May 24,"Nimer, Nabil A.",Can J Infect Dis Med Microbiol,,,True
c2a4b60c4285348cbc44c501adc3dbdc4088870b,PMC,Perturbation of Intracellular Cholesterol and Fatty Acid Homeostasis During Flavivirus Infections,http://dx.doi.org/10.3389/fimmu.2018.01276,PMC5994796,29915602,CC BY,"Cellular lipid homeostasis is maintained through an intricately linked array of anabolic and catabolic pathways. Upon flavivirus infections, these are significantly altered: on the one hand, these viruses can co-opt lipid metabolic pathways to generate ATP to facilitate replication, or to synthesize membrane components to generate replication sites; on the other hand, more recent evidence suggests counter strategies employed by host cells, which actively modulate several of these networks in response to infection, enhancing interferon signaling by doing so, and thus creating an antiviral environment. In this review, we discuss recent data on mechanisms of alteration of lipid metabolic pathways during infection by flaviviruses, with a focus on cholesterol and fatty acid biosynthesis, which can be manipulated by the invading viruses to support replication, but can also be modulated by the host immune system itself, as a means to fight infection.",2018 Jun 4,"['Pombo, Joao Palma', 'Sanyal, Sumana']",Front Immunol,,,True
ade5723fc8cfb81cb7bc212d21539f1fe53fe218,PMC,Differential Evolution of Antiretroviral Restriction Factors in Pteropid Bats as Revealed by APOBEC3 Gene Complexity,http://dx.doi.org/10.1093/molbev/msy048,PMC5995163,29617834,CC BY,"Bats have attracted attention in recent years as important reservoirs of viruses deadly to humans and other mammals. These infections are typically nonpathogenic in bats raising questions about innate immune differences that might exist between bats and other mammals. The APOBEC3 gene family encodes antiviral DNA cytosine deaminases with important roles in the suppression of diverse viruses and genomic parasites. Here, we characterize pteropid APOBEC3 genes and show that species within the genus Pteropus possess the largest and most diverse array of APOBEC3 genes identified in any mammal reported to date. Several bat APOBEC3 proteins are antiviral as demonstrated by restriction of retroviral infectivity using HIV-1 as a model, and recombinant A3Z1 subtypes possess strong DNA deaminase activity. These genes represent the first group of antiviral restriction factors identified in bats with extensive diversification relative to homologues in other mammals.",2018 Jul 29,"['Hayward, Joshua A', 'Tachedjian, Mary', 'Cui, Jie', 'Cheng, Adam Z', 'Johnson, Adam', 'Baker, Michelle L', 'Harris, Reuben S', 'Wang, Lin-Fa', 'Tachedjian, Gilda']",Mol Biol Evol,,,True
7fedb6619c6cdd969d50307211e7a77aeb9a8893,PMC,viGEN: An Open Source Pipeline for the Detection and Quantification of Viral RNA in Human Tumors,http://dx.doi.org/10.3389/fmicb.2018.01172,PMC5996193,29922260,CC BY,"An estimated 17% of cancers worldwide are associated with infectious causes. The extent and biological significance of viral presence/infection in actual tumor samples is generally unknown but could be measured using human transcriptome (RNA-seq) data from tumor samples. We present an open source bioinformatics pipeline viGEN, which allows for not only the detection and quantification of viral RNA, but also variants in the viral transcripts. The pipeline includes 4 major modules: The first module aligns and filter out human RNA sequences; the second module maps and count (remaining un-aligned) reads against reference genomes of all known and sequenced human viruses; the third module quantifies read counts at the individual viral-gene level thus allowing for downstream differential expression analysis of viral genes between case and controls groups. The fourth module calls variants in these viruses. To the best of our knowledge, there are no publicly available pipelines or packages that would provide this type of complete analysis in one open source package. In this paper, we applied the viGEN pipeline to two case studies. We first demonstrate the working of our pipeline on a large public dataset, the TCGA cervical cancer cohort. In the second case study, we performed an in-depth analysis on a small focused study of TCGA liver cancer patients. In the latter cohort, we performed viral-gene quantification, viral-variant extraction and survival analysis. This allowed us to find differentially expressed viral-transcripts and viral-variants between the groups of patients, and connect them to clinical outcome. From our analyses, we show that we were able to successfully detect the human papilloma virus among the TCGA cervical cancer patients. We compared the viGEN pipeline with two metagenomics tools and demonstrate similar sensitivity/specificity. We were also able to quantify viral-transcripts and extract viral-variants using the liver cancer dataset. The results presented corresponded with published literature in terms of rate of detection, and impact of several known variants of HBV genome. This pipeline is generalizable, and can be used to provide novel biological insights into microbial infections in complex diseases and tumorigeneses. Our viral pipeline could be used in conjunction with additional type of immuno-oncology analysis based on RNA-seq data of host RNA for cancer immunology applications. The source code, with example data and tutorial is available at: https://github.com/ICBI/viGEN/.",2018 Jun 5,"['Bhuvaneshwar, Krithika', 'Song, Lei', 'Madhavan, Subha', 'Gusev, Yuriy']",Front Microbiol,,,True
1a8a5dd7220551bd5c7632a338d57c8fd5252c37,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.18.010618,PMC5996205,29904217,CC BY,,2018 Jun 1,,Bull World Health Organ,,,False
e12fc1a31129f8aa683a597e3899199409cc67f6,PMC,"Detection and phylogenetic characterization of arbovirus dual-infections among persons during a chikungunya fever outbreak, Haiti 2014",http://dx.doi.org/10.1371/journal.pntd.0006505,PMC5997359,29851952,CC BY,"In the context of recent arbovirus epidemics, questions about the frequency of simultaneous infection of patients with different arbovirus species have been raised. In 2014, a major Chikungunya virus (CHIKV) epidemic impacted the Caribbean and South America. As part of ongoing screening of schoolchildren presenting with acute undifferentiated febrile illness in rural Haiti, we used RT-PCR to identify CHIKV infections in 82 of 100 children with this diagnosis during May—August 2014. Among these, eight were infected with a second arbovirus: six with Zika virus (ZIKV), one with Dengue virus serotype 2, and one with Mayaro virus (MAYV). These dual infections were only detected following culture of the specimen, suggesting low viral loads of the co-infecting species. Phylogenetic analyses indicated that the ZIKV and MAYV strains differ from those detected later in 2014 and 2015, respectively. Moreover, CHIKV and ZIKV strains from co-infected patients clustered monophyletically in their respective phylogeny, and clock calibration traced back the common ancestor of each clade to an overlapping timeframe of introduction of these arboviruses onto the island.",2018 May 31,"['White, Sarah K.', 'Mavian, Carla', 'Elbadry, Maha A.', 'Beau De Rochars, Valery Madsen', 'Paisie, Taylor', 'Telisma, Taina', 'Salemi, Marco', 'Lednicky, John A.', 'Morris, J. Glenn']",PLoS Negl Trop Dis,,,True
914277be16ff14707b638bb5a86ef4c5f2aebc89,PMC,"Detection and phylogenetic characterization of arbovirus dual-infections among persons during a chikungunya fever outbreak, Haiti 2014",http://dx.doi.org/10.1371/journal.pntd.0006505,PMC5997359,29851952,CC BY,"In the context of recent arbovirus epidemics, questions about the frequency of simultaneous infection of patients with different arbovirus species have been raised. In 2014, a major Chikungunya virus (CHIKV) epidemic impacted the Caribbean and South America. As part of ongoing screening of schoolchildren presenting with acute undifferentiated febrile illness in rural Haiti, we used RT-PCR to identify CHIKV infections in 82 of 100 children with this diagnosis during May—August 2014. Among these, eight were infected with a second arbovirus: six with Zika virus (ZIKV), one with Dengue virus serotype 2, and one with Mayaro virus (MAYV). These dual infections were only detected following culture of the specimen, suggesting low viral loads of the co-infecting species. Phylogenetic analyses indicated that the ZIKV and MAYV strains differ from those detected later in 2014 and 2015, respectively. Moreover, CHIKV and ZIKV strains from co-infected patients clustered monophyletically in their respective phylogeny, and clock calibration traced back the common ancestor of each clade to an overlapping timeframe of introduction of these arboviruses onto the island.",2018 May 31,"['White, Sarah K.', 'Mavian, Carla', 'Elbadry, Maha A.', 'Beau De Rochars, Valery Madsen', 'Paisie, Taylor', 'Telisma, Taina', 'Salemi, Marco', 'Lednicky, John A.', 'Morris, J. Glenn']",PLoS Negl Trop Dis,,,False
ed8de82d7efedd7c82dd593ce175402b94edbf8e,PMC,"Detection and phylogenetic characterization of arbovirus dual-infections among persons during a chikungunya fever outbreak, Haiti 2014",http://dx.doi.org/10.1371/journal.pntd.0006505,PMC5997359,29851952,CC BY,"In the context of recent arbovirus epidemics, questions about the frequency of simultaneous infection of patients with different arbovirus species have been raised. In 2014, a major Chikungunya virus (CHIKV) epidemic impacted the Caribbean and South America. As part of ongoing screening of schoolchildren presenting with acute undifferentiated febrile illness in rural Haiti, we used RT-PCR to identify CHIKV infections in 82 of 100 children with this diagnosis during May—August 2014. Among these, eight were infected with a second arbovirus: six with Zika virus (ZIKV), one with Dengue virus serotype 2, and one with Mayaro virus (MAYV). These dual infections were only detected following culture of the specimen, suggesting low viral loads of the co-infecting species. Phylogenetic analyses indicated that the ZIKV and MAYV strains differ from those detected later in 2014 and 2015, respectively. Moreover, CHIKV and ZIKV strains from co-infected patients clustered monophyletically in their respective phylogeny, and clock calibration traced back the common ancestor of each clade to an overlapping timeframe of introduction of these arboviruses onto the island.",2018 May 31,"['White, Sarah K.', 'Mavian, Carla', 'Elbadry, Maha A.', 'Beau De Rochars, Valery Madsen', 'Paisie, Taylor', 'Telisma, Taina', 'Salemi, Marco', 'Lednicky, John A.', 'Morris, J. Glenn']",PLoS Negl Trop Dis,,,False
f1c879ab922020f7fea0546619513e46a352a608,PMC,"Detection and phylogenetic characterization of arbovirus dual-infections among persons during a chikungunya fever outbreak, Haiti 2014",http://dx.doi.org/10.1371/journal.pntd.0006505,PMC5997359,29851952,CC BY,"In the context of recent arbovirus epidemics, questions about the frequency of simultaneous infection of patients with different arbovirus species have been raised. In 2014, a major Chikungunya virus (CHIKV) epidemic impacted the Caribbean and South America. As part of ongoing screening of schoolchildren presenting with acute undifferentiated febrile illness in rural Haiti, we used RT-PCR to identify CHIKV infections in 82 of 100 children with this diagnosis during May—August 2014. Among these, eight were infected with a second arbovirus: six with Zika virus (ZIKV), one with Dengue virus serotype 2, and one with Mayaro virus (MAYV). These dual infections were only detected following culture of the specimen, suggesting low viral loads of the co-infecting species. Phylogenetic analyses indicated that the ZIKV and MAYV strains differ from those detected later in 2014 and 2015, respectively. Moreover, CHIKV and ZIKV strains from co-infected patients clustered monophyletically in their respective phylogeny, and clock calibration traced back the common ancestor of each clade to an overlapping timeframe of introduction of these arboviruses onto the island.",2018 May 31,"['White, Sarah K.', 'Mavian, Carla', 'Elbadry, Maha A.', 'Beau De Rochars, Valery Madsen', 'Paisie, Taylor', 'Telisma, Taina', 'Salemi, Marco', 'Lednicky, John A.', 'Morris, J. Glenn']",PLoS Negl Trop Dis,,,False
2ad8032804b3deb79b634cfbad52efbf2f90da76,PMC,Antiviral Activity of Novel Quinoline Derivatives against Dengue Virus Serotype 2,http://dx.doi.org/10.3390/molecules23030672,PMC5997395,29547522,CC BY,"Dengue virus causes dengue fever, a debilitating disease with an increasing incidence in many tropical and subtropical territories. So far, there are no effective antivirals licensed to treat this virus. Here we describe the synthesis and antiviral activity evaluation of two compounds based on the quinoline scaffold, which has shown potential for the development of molecules with various biological activities. Two of the tested compounds showed dose-dependent inhibition of dengue virus serotype 2 in the low and sub micromolar range. The compounds 1 and 2 were also able to impair the accumulation of the viral envelope glycoprotein in infected cells, while showing no sign of direct virucidal activity and acting possibly through a mechanism involving the early stages of the infection. The results are congruent with previously reported data showing the potential of quinoline derivatives as a promising scaffold for the development of new antivirals against this important virus.",2018 Mar 16,"['de la Guardia, Carolina', 'Stephens, David E.', 'Dang, Hang T.', 'Quijada, Mario', 'Larionov, Oleg V.', 'Lleonart, Ricardo']",Molecules,,,True
50374c4c895cc05eb43c80e50290213d54a75e81,PMC,Antiviral Activity of Novel Quinoline Derivatives against Dengue Virus Serotype 2,http://dx.doi.org/10.3390/molecules23030672,PMC5997395,29547522,CC BY,"Dengue virus causes dengue fever, a debilitating disease with an increasing incidence in many tropical and subtropical territories. So far, there are no effective antivirals licensed to treat this virus. Here we describe the synthesis and antiviral activity evaluation of two compounds based on the quinoline scaffold, which has shown potential for the development of molecules with various biological activities. Two of the tested compounds showed dose-dependent inhibition of dengue virus serotype 2 in the low and sub micromolar range. The compounds 1 and 2 were also able to impair the accumulation of the viral envelope glycoprotein in infected cells, while showing no sign of direct virucidal activity and acting possibly through a mechanism involving the early stages of the infection. The results are congruent with previously reported data showing the potential of quinoline derivatives as a promising scaffold for the development of new antivirals against this important virus.",2018 Mar 16,"['de la Guardia, Carolina', 'Stephens, David E.', 'Dang, Hang T.', 'Quijada, Mario', 'Larionov, Oleg V.', 'Lleonart, Ricardo']",Molecules,,,False
7678c5127902d1cf20860600647cddec300c9e7e,PMC,Prion-like Domains in Eukaryotic Viruses,http://dx.doi.org/10.1038/s41598-018-27256-w,PMC5997743,29895872,CC BY,"Prions are proteins that can self-propagate, leading to the misfolding of proteins. In addition to the previously demonstrated pathogenic roles of prions during the development of different mammalian diseases, including neurodegenerative diseases, they have recently been shown to represent an important functional component in many prokaryotic and eukaryotic organisms and bacteriophages, confirming the previously unexplored important regulatory and functional roles. However, an in-depth analysis of these domains in eukaryotic viruses has not been performed. Here, we examined the presence of prion-like proteins in eukaryotic viruses that play a primary role in different ecosystems and that are associated with emerging diseases in humans. We identified relevant functional associations in different viral processes and regularities in their presence at different taxonomic levels. Using the prion-like amino-acid composition computational algorithm, we detected 2679 unique putative prion-like domains within 2,742,160 publicly available viral protein sequences. Our findings indicate that viral prion-like proteins can be found in different viruses of insects, plants, mammals, and humans. The analysis performed here demonstrated common patterns in the distribution of prion-like domains across viral orders and families, and revealed probable functional associations with different steps of viral replication and interaction with host cells. These data allow the identification of the viral prion-like proteins as potential novel regulators of viral infections.",2018 Jun 12,"['Tetz, George', 'Tetz, Victor']",Sci Rep,,,False
c8b6c6e27819d9aab5d8f6f9421b0e5eb1aab32a,PMC,Prion-like Domains in Eukaryotic Viruses,http://dx.doi.org/10.1038/s41598-018-27256-w,PMC5997743,29895872,CC BY,"Prions are proteins that can self-propagate, leading to the misfolding of proteins. In addition to the previously demonstrated pathogenic roles of prions during the development of different mammalian diseases, including neurodegenerative diseases, they have recently been shown to represent an important functional component in many prokaryotic and eukaryotic organisms and bacteriophages, confirming the previously unexplored important regulatory and functional roles. However, an in-depth analysis of these domains in eukaryotic viruses has not been performed. Here, we examined the presence of prion-like proteins in eukaryotic viruses that play a primary role in different ecosystems and that are associated with emerging diseases in humans. We identified relevant functional associations in different viral processes and regularities in their presence at different taxonomic levels. Using the prion-like amino-acid composition computational algorithm, we detected 2679 unique putative prion-like domains within 2,742,160 publicly available viral protein sequences. Our findings indicate that viral prion-like proteins can be found in different viruses of insects, plants, mammals, and humans. The analysis performed here demonstrated common patterns in the distribution of prion-like domains across viral orders and families, and revealed probable functional associations with different steps of viral replication and interaction with host cells. These data allow the identification of the viral prion-like proteins as potential novel regulators of viral infections.",2018 Jun 12,"['Tetz, George', 'Tetz, Victor']",Sci Rep,,,False
cc099607ce01569fed0def2e9651d5e594868bfd,PMC,Prion-like Domains in Eukaryotic Viruses,http://dx.doi.org/10.1038/s41598-018-27256-w,PMC5997743,29895872,CC BY,"Prions are proteins that can self-propagate, leading to the misfolding of proteins. In addition to the previously demonstrated pathogenic roles of prions during the development of different mammalian diseases, including neurodegenerative diseases, they have recently been shown to represent an important functional component in many prokaryotic and eukaryotic organisms and bacteriophages, confirming the previously unexplored important regulatory and functional roles. However, an in-depth analysis of these domains in eukaryotic viruses has not been performed. Here, we examined the presence of prion-like proteins in eukaryotic viruses that play a primary role in different ecosystems and that are associated with emerging diseases in humans. We identified relevant functional associations in different viral processes and regularities in their presence at different taxonomic levels. Using the prion-like amino-acid composition computational algorithm, we detected 2679 unique putative prion-like domains within 2,742,160 publicly available viral protein sequences. Our findings indicate that viral prion-like proteins can be found in different viruses of insects, plants, mammals, and humans. The analysis performed here demonstrated common patterns in the distribution of prion-like domains across viral orders and families, and revealed probable functional associations with different steps of viral replication and interaction with host cells. These data allow the identification of the viral prion-like proteins as potential novel regulators of viral infections.",2018 Jun 12,"['Tetz, George', 'Tetz, Victor']",Sci Rep,,,False
e54f17d565220a7de798d52bfc99233c536f7ab9,PMC,Prion-like Domains in Eukaryotic Viruses,http://dx.doi.org/10.1038/s41598-018-27256-w,PMC5997743,29895872,CC BY,"Prions are proteins that can self-propagate, leading to the misfolding of proteins. In addition to the previously demonstrated pathogenic roles of prions during the development of different mammalian diseases, including neurodegenerative diseases, they have recently been shown to represent an important functional component in many prokaryotic and eukaryotic organisms and bacteriophages, confirming the previously unexplored important regulatory and functional roles. However, an in-depth analysis of these domains in eukaryotic viruses has not been performed. Here, we examined the presence of prion-like proteins in eukaryotic viruses that play a primary role in different ecosystems and that are associated with emerging diseases in humans. We identified relevant functional associations in different viral processes and regularities in their presence at different taxonomic levels. Using the prion-like amino-acid composition computational algorithm, we detected 2679 unique putative prion-like domains within 2,742,160 publicly available viral protein sequences. Our findings indicate that viral prion-like proteins can be found in different viruses of insects, plants, mammals, and humans. The analysis performed here demonstrated common patterns in the distribution of prion-like domains across viral orders and families, and revealed probable functional associations with different steps of viral replication and interaction with host cells. These data allow the identification of the viral prion-like proteins as potential novel regulators of viral infections.",2018 Jun 12,"['Tetz, George', 'Tetz, Victor']",Sci Rep,,,False
c8076f2ae9a3076f5f1ce54ecbc4a39274c9c21f,PMC,Prion-like Domains in Eukaryotic Viruses,http://dx.doi.org/10.1038/s41598-018-27256-w,PMC5997743,29895872,CC BY,"Prions are proteins that can self-propagate, leading to the misfolding of proteins. In addition to the previously demonstrated pathogenic roles of prions during the development of different mammalian diseases, including neurodegenerative diseases, they have recently been shown to represent an important functional component in many prokaryotic and eukaryotic organisms and bacteriophages, confirming the previously unexplored important regulatory and functional roles. However, an in-depth analysis of these domains in eukaryotic viruses has not been performed. Here, we examined the presence of prion-like proteins in eukaryotic viruses that play a primary role in different ecosystems and that are associated with emerging diseases in humans. We identified relevant functional associations in different viral processes and regularities in their presence at different taxonomic levels. Using the prion-like amino-acid composition computational algorithm, we detected 2679 unique putative prion-like domains within 2,742,160 publicly available viral protein sequences. Our findings indicate that viral prion-like proteins can be found in different viruses of insects, plants, mammals, and humans. The analysis performed here demonstrated common patterns in the distribution of prion-like domains across viral orders and families, and revealed probable functional associations with different steps of viral replication and interaction with host cells. These data allow the identification of the viral prion-like proteins as potential novel regulators of viral infections.",2018 Jun 12,"['Tetz, George', 'Tetz, Victor']",Sci Rep,,,False
be7d22507f45b2b2927f91d16d7b89c1bf2c35cf,PMC,Prion-like Domains in Eukaryotic Viruses,http://dx.doi.org/10.1038/s41598-018-27256-w,PMC5997743,29895872,CC BY,"Prions are proteins that can self-propagate, leading to the misfolding of proteins. In addition to the previously demonstrated pathogenic roles of prions during the development of different mammalian diseases, including neurodegenerative diseases, they have recently been shown to represent an important functional component in many prokaryotic and eukaryotic organisms and bacteriophages, confirming the previously unexplored important regulatory and functional roles. However, an in-depth analysis of these domains in eukaryotic viruses has not been performed. Here, we examined the presence of prion-like proteins in eukaryotic viruses that play a primary role in different ecosystems and that are associated with emerging diseases in humans. We identified relevant functional associations in different viral processes and regularities in their presence at different taxonomic levels. Using the prion-like amino-acid composition computational algorithm, we detected 2679 unique putative prion-like domains within 2,742,160 publicly available viral protein sequences. Our findings indicate that viral prion-like proteins can be found in different viruses of insects, plants, mammals, and humans. The analysis performed here demonstrated common patterns in the distribution of prion-like domains across viral orders and families, and revealed probable functional associations with different steps of viral replication and interaction with host cells. These data allow the identification of the viral prion-like proteins as potential novel regulators of viral infections.",2018 Jun 12,"['Tetz, George', 'Tetz, Victor']",Sci Rep,,,True
2eb06838c62a16822b1a0aa7be0a43d380025f50,PMC,"Ingestion of Exopolymers from Aureobasidium pullulans Reduces the Duration of Cold and Flu Symptoms: A Randomized, Placebo-Controlled Intervention Study",http://dx.doi.org/10.1155/2018/9024295,PMC5998159,30002717,CC BY,"AIM: The objective of the study was to assess the efficacy of exopolymers from Aureobasidium pullulans (EAP) on the incidence of colds and flu in healthy adults. METHODS: We conducted a randomized, double-blind, placebo-controlled study at the onset of the influenza season. A total of 76 subjects (30–70 years of age) were recruited from the general population. The subjects were instructed to take one capsule per day of either EAP or a placebo for a period of 8 weeks. The duration of cold and flu symptoms, a primary variable in assessing effectiveness, and serum cytokine levels as well as WBC counts as secondary variables were also evaluated. RESULTS: EAP was associated with a statistically significant decrease in the duration of cold and flu symptoms, a primary variable in assessing effectiveness. Although cold and flu symptom levels were not significantly different at a significance level of 5%, the cold and flu symptom levels of the EAP group were less severe compared to the placebo group. No statistically significant changes of serum cytokine levels as well as WBC counts were observed. CONCLUSION: The results showed that EAP is a useful pharmaceutical and functional food material for preventing and treating colds and flu.",2018 May 30,"['Lim, Jong-Min', 'Do, Eunju', 'Park, Dong-Chan', 'Jung, Go-Woon', 'Cho, Hyung-Rae', 'Lee, Seo-Young', 'Shin, Jae Wook', 'Baek, Kyung Min', 'Choi, Jae-Suk']",Evid Based Complement Alternat Med,,,True
27ae3f39b9760d891f7c8f2fd3d1b6d5e038f232,PMC,Comparison data of a two-target real-time PCR assay with and without an internal control in detecting Salmonella enterica from cattle lymph nodes,http://dx.doi.org/10.1016/j.dib.2018.04.051,PMC5998743,29904683,CC BY,"A real-time PCR (qPCR) assay targeting on invA and pagC genes was developed and validated for the detection and quantification of Salmonella enterica strains (Bai et al., 2018) [1]. A host gene, normally an endogenous housekeeping gene (Beer-Davidson et al., 2018; Poon et al., 2004) [2,3], or an irrelevant exogenous gene (Cheng et al., 2015; Sedlak et al., 2014) [4,5] has been widely used as an internal control to monitor nucleic acid extraction efficiencies and potential PCR inhibitions in PCR-based detection assays. An endogenous internal control designed based on the 18S rRNA gene was used in the above-mentioned qPCR assay. This 18S rRNA internal control amplifies the target gene in multiple species including bovine, swine, ovine, caprine and cervine. Data was generated by the duplex qPCR assay on 138 enriched cattle lymph node samples without the internal control, and compared with data on the same samples tested by the triplex qPCR assay that has the 18S rRNA gene as internal control. Threshold cycle (Ct) data for the duplex and the triplex qPCR on the 138 samples were similar, and are presented in this brief report.",2018 Apr 22,"['Bai, Jianfa', 'Trinetta, Valentina', 'Shi, Xiaorong', 'Noll, Lance W.', 'Magossi, Gabriela', 'Zheng, Wanglong', 'Porter, Elizabeth P.', 'Cernicchiaro, Natalia', 'Renter, David G.', 'Nagaraja, Tiruvoor G.']",Data Brief,,,False
ffa8530e592ea6d3d49453e91ecb90a3bfd099df,PMC,Generation and comparative genomics of synthetic dengue viruses,http://dx.doi.org/10.1186/s12859-018-2132-3,PMC5998877,29745863,CC BY,"BACKGROUND: Synthetic virology is an important multidisciplinary scientific field, with emerging applications in biotechnology and medicine, aiming at developing methods to generate and engineer synthetic viruses. In particular, many of the RNA viruses, including among others the Dengue and Zika, are widespread pathogens of significant importance to human health. The ability to design and synthesize such viruses may contribute to exploring novel approaches for developing vaccines and virus based therapies. RESULTS: Here we develop a full multidisciplinary pipeline for generation and analysis of synthetic RNA viruses and specifically apply it to Dengue virus serotype 2 (DENV-2). The major steps of the pipeline include comparative genomics of endogenous and synthetic viral strains. Specifically, we show that although the synthetic DENV-2 viruses were found to have lower nucleotide variability, their phenotype, as reflected in the study of the AG129 mouse model morbidity, RNA levels, and neutralization antibodies, is similar or even more pathogenic in comparison to the wildtype master strain. Additionally, the highly variable positions, identified in the analyzed DENV-2 population, were found to overlap with less conserved homologous positions in Zika virus and other Dengue serotypes. These results may suggest that synthetic DENV-2 could enhance virulence if the correct sequence is selected. CONCLUSIONS: The approach reported in this study can be used to generate and analyze synthetic RNA viruses both on genotypic and on phenotypic level. It could be applied for understanding the functionality and the fitness effects of any set of mutations in viral RNA and for editing RNA viruses for various target applications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-018-2132-3) contains supplementary material, which is available to authorized users.",2018 May 8,"['Goz, Eli', 'Tsalenchuck, Yael', 'Benaroya, Rony Oren', 'Zafrir, Zohar', 'Atar, Shimshi', 'Altman, Tahel', 'Julander, Justin', 'Tuller, Tamir']",BMC Bioinformatics,,,False
edcf92549f64338ff9e1d47d45b150ef4d6177b0,PMC,Generation and comparative genomics of synthetic dengue viruses,http://dx.doi.org/10.1186/s12859-018-2132-3,PMC5998877,29745863,CC BY,"BACKGROUND: Synthetic virology is an important multidisciplinary scientific field, with emerging applications in biotechnology and medicine, aiming at developing methods to generate and engineer synthetic viruses. In particular, many of the RNA viruses, including among others the Dengue and Zika, are widespread pathogens of significant importance to human health. The ability to design and synthesize such viruses may contribute to exploring novel approaches for developing vaccines and virus based therapies. RESULTS: Here we develop a full multidisciplinary pipeline for generation and analysis of synthetic RNA viruses and specifically apply it to Dengue virus serotype 2 (DENV-2). The major steps of the pipeline include comparative genomics of endogenous and synthetic viral strains. Specifically, we show that although the synthetic DENV-2 viruses were found to have lower nucleotide variability, their phenotype, as reflected in the study of the AG129 mouse model morbidity, RNA levels, and neutralization antibodies, is similar or even more pathogenic in comparison to the wildtype master strain. Additionally, the highly variable positions, identified in the analyzed DENV-2 population, were found to overlap with less conserved homologous positions in Zika virus and other Dengue serotypes. These results may suggest that synthetic DENV-2 could enhance virulence if the correct sequence is selected. CONCLUSIONS: The approach reported in this study can be used to generate and analyze synthetic RNA viruses both on genotypic and on phenotypic level. It could be applied for understanding the functionality and the fitness effects of any set of mutations in viral RNA and for editing RNA viruses for various target applications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-018-2132-3) contains supplementary material, which is available to authorized users.",2018 May 8,"['Goz, Eli', 'Tsalenchuck, Yael', 'Benaroya, Rony Oren', 'Zafrir, Zohar', 'Atar, Shimshi', 'Altman, Tahel', 'Julander, Justin', 'Tuller, Tamir']",BMC Bioinformatics,,,True
258dc6960914cb934076d169f8c02d51883cf571,PMC,Elevated plasma angiotensin converting enzyme 2 activity is an independent predictor of major adverse cardiac events in patients with obstructive coronary artery disease,http://dx.doi.org/10.1371/journal.pone.0198144,PMC5999069,29897923,CC BY,"BACKGROUND: Angiotensin converting enzyme 2 (ACE2) is an endogenous regulator of the renin angiotensin system. Increased circulating ACE2 predicts adverse outcomes in patients with heart failure (HF), but it is unknown if elevated plasma ACE2 activity predicts major adverse cardiovascular events (MACE) in patients with obstructive coronary artery disease (CAD). METHODS: We prospectively recruited patients with obstructive CAD (defined as ≥50% stenosis of the left main coronary artery and/or ≥70% stenosis in ≥ 1 other major epicardial vessel on invasive coronary angiography) and measured plasma ACE2 activity. Patients were followed up to determine if circulating ACE2 activity levels predicted the primary endpoint of MACE (cardiovascular mortality, HF or myocardial infarction). RESULTS: We recruited 79 patients with obstructive coronary artery disease. The median (IQR) plasma ACE2 activity was 29.3 pmol/ml/min [21.2–41.2]. Over a median follow up of 10.5 years [9.6–10.8years], MACE occurred in 46% of patients (36 events). On Kaplan-Meier analysis, above-median plasma ACE2 activity was associated with MACE (log-rank test, p = 0.035) and HF hospitalisation (p = 0.01). After Cox multivariable adjustment, log ACE2 activity remained an independent predictor of MACE (hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.24–4.72, p = 0.009) and HF hospitalisation (HR: 4.03, 95% CI: 1.42–11.5, p = 0.009). CONCLUSIONS: Plasma ACE2 activity independently increased the hazard of adverse long-term cardiovascular outcomes in patients with obstructive CAD.",2018 Jun 13,"['Ramchand, Jay', 'Patel, Sheila K.', 'Srivastava, Piyush M.', 'Farouque, Omar', 'Burrell, Louise M.']",PLoS One,,,True
8972bc579c78bdb435fc733cea252be83534465d,PMC,A barnavirus sequence mined from a transcriptome of the Antarctic pearlwort Colobanthus quitensis,http://dx.doi.org/10.1007/s00705-018-3794-x,PMC5999160,29516246,CC BY,"Because so few viruses in the family Barnaviridae have been reported, we searched for more of them in public sequence databases. Here, we report the complete coding sequence of Colobanthus quitensis associated barnavirus 1, mined from a transcriptome of the Antarctic pearlwort Colobanthus quitensis. The 4.2-kb plus-strand sequence of this virus encompasses four main open reading frames (ORFs), as expected for barnaviruses, including ORFs for a protease-containing polyprotein, an RNA-dependent RNA polymerase whose translation appears to rely on − 1 ribosomal frameshifting, and a capsid protein that is likely to be translated from a subgenomic RNA. The possible derivation of this virus from a fungus associated with C. quitensis is discussed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-018-3794-x) contains supplementary material, which is available to authorized users.",2018 Mar 7,"['Nibert, Max L.', 'Manny, Austin R.', 'Debat, Humberto J.', 'Firth, Andrew E.', 'Bertini, Laura', 'Caruso, Carla']",Arch Virol,,,False
9d9347a3f4d7fe21a8d2bdc9aa593830a6856630,PMC,A barnavirus sequence mined from a transcriptome of the Antarctic pearlwort Colobanthus quitensis,http://dx.doi.org/10.1007/s00705-018-3794-x,PMC5999160,29516246,CC BY,"Because so few viruses in the family Barnaviridae have been reported, we searched for more of them in public sequence databases. Here, we report the complete coding sequence of Colobanthus quitensis associated barnavirus 1, mined from a transcriptome of the Antarctic pearlwort Colobanthus quitensis. The 4.2-kb plus-strand sequence of this virus encompasses four main open reading frames (ORFs), as expected for barnaviruses, including ORFs for a protease-containing polyprotein, an RNA-dependent RNA polymerase whose translation appears to rely on − 1 ribosomal frameshifting, and a capsid protein that is likely to be translated from a subgenomic RNA. The possible derivation of this virus from a fungus associated with C. quitensis is discussed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-018-3794-x) contains supplementary material, which is available to authorized users.",2018 Mar 7,"['Nibert, Max L.', 'Manny, Austin R.', 'Debat, Humberto J.', 'Firth, Andrew E.', 'Bertini, Laura', 'Caruso, Carla']",Arch Virol,,,True
91296a9926298b0f89b83bc2dcf198af41827ce4,PMC,"Middle East respiratory syndrome coronavirus specific antibodies in naturally exposed Israeli llamas, alpacas and camels",http://dx.doi.org/10.1016/j.onehlt.2018.05.002,PMC6000904,29911167,CC BY,"Thus far, no human MERS-CoV infections have been reported from Israel. Evidence for the circulation of MERS-CoV in dromedaries has been reported from almost all the countries of the Middle East, except Israel. Therefore, we aimed to analyze MERS-CoV infection in Israeli camelids, sampled between 2012 and 2017. A total of 411 camels, 102 alpacas and 19 llamas' sera were tested for the presence of antibodies to MERS-CoV. Our findings indicate a lower MERS-CoV seropositivity among Israeli dromedaries than in the surrounding countries, and for the first time naturally infected llamas were identified. In addition, nasal swabs of 661 camels, alpacas and lamas, obtained from January 2015 to December 2017, were tested for the presence of MERS-CoV RNA. All nasal swabs were negative, indicating no evidence for MERS-CoV active circulation in these camelids during that time period.",2018 May 4,"['David, Dan', 'Rotenberg, Ditza', 'Khinich, Evgeny', 'Erster, Oran', 'Bardenstein, Svetlana', 'van Straten, Michael', 'Okba, Nisreen M.A.', 'Raj, Stalin V.', 'Haagmans, Bart L.', 'Miculitzki, Marcelo', 'Davidson, Irit']",One Health,,,False
20e1ac88c8ad15a2b3bd9be62dd1c936fc92afaa,PMC,"Quarantine, isolation and the duty of easy rescue in public health",http://dx.doi.org/10.1111/dewb.12165,PMC6001516,28922559,CC BY,"We address the issue of whether, why and under what conditions, quarantine and isolation are morally justified, with a particular focus on measures implemented in the developing world. We argue that the benefits of quarantine and isolation justify some level of coercion or compulsion by the state, but that the state should be able to provide the strongest justification possible for implementing such measures. While a constrained form of consequentialism might provide a justification for such public health interventions, we argue that a stronger justification is provided by a principle of State Enforced Easy Rescue: a state may permissibly compel individuals to engage in activities that entail a small cost to them but a large benefit to others, because individuals have a moral duty of easy rescue to engage in those activities. The principle of State Enforced Easy Rescue gives rise to an Obligation Enforcement Requirement: the state should create the conditions such that submitting to coercive or compulsive measures becomes a fundamental moral duty of individuals, i.e. a duty of easy rescue. When the state can create such conditions, it has the strongest justification possible for implementing coercive or compulsive measures, because individuals have a moral duty to temporarily relinquish the rights that such measures would infringe. Our argument has significant implications for how public health emergencies in the developing world should be tackled. Where isolation and quarantine measures are necessary, states or the international community have a moral obligation to provide certain benefits to those quarantined or isolated.",2018 Jun 18,"['Giubilini, Alberto', 'Douglas, Thomas', 'Maslen, Hannah', 'Savulescu, Julian']",Dev World Bioeth,,,False
7cbfd22d36a109e840f1572eb2fcf6794b73070b,PMC,Improving early epidemiological assessment of emerging Aedes-transmitted epidemics using historical data,http://dx.doi.org/10.1371/journal.pntd.0006526,PMC6002135,29864129,CC BY,"Model-based epidemiological assessment is useful to support decision-making at the beginning of an emerging Aedes-transmitted outbreak. However, early forecasts are generally unreliable as little information is available in the first few incidence data points. Here, we show how past Aedes-transmitted epidemics help improve these predictions. The approach was applied to the 2015–2017 Zika virus epidemics in three islands of the French West Indies, with historical data including other Aedes-transmitted diseases (chikungunya and Zika) in the same and other locations. Hierarchical models were used to build informative a priori distributions on the reproduction ratio and the reporting rates. The accuracy and sharpness of forecasts improved substantially when these a priori distributions were used in models for prediction. For example, early forecasts of final epidemic size obtained without historical information were 3.3 times too high on average (range: 0.2 to 5.8) with respect to the eventual size, but were far closer (1.1 times the real value on average, range: 0.4 to 1.5) using information on past CHIKV epidemics in the same places. Likewise, the 97.5% upper bound for maximal incidence was 15.3 times (range: 2.0 to 63.1) the actual peak incidence, and became much sharper at 2.4 times (range: 1.3 to 3.9) the actual peak incidence with informative a priori distributions. Improvements were more limited for the date of peak incidence and the total duration of the epidemic. The framework can adapt to all forecasting models at the early stages of emerging Aedes-transmitted outbreaks.",2018 Jun 4,"['Riou, Julien', 'Poletto, Chiara', 'Boëlle, Pierre-Yves']",PLoS Negl Trop Dis,,,True
b1fa74682266ab3d64275b8f738e8e9a37732efe,PMC,Improving early epidemiological assessment of emerging Aedes-transmitted epidemics using historical data,http://dx.doi.org/10.1371/journal.pntd.0006526,PMC6002135,29864129,CC BY,"Model-based epidemiological assessment is useful to support decision-making at the beginning of an emerging Aedes-transmitted outbreak. However, early forecasts are generally unreliable as little information is available in the first few incidence data points. Here, we show how past Aedes-transmitted epidemics help improve these predictions. The approach was applied to the 2015–2017 Zika virus epidemics in three islands of the French West Indies, with historical data including other Aedes-transmitted diseases (chikungunya and Zika) in the same and other locations. Hierarchical models were used to build informative a priori distributions on the reproduction ratio and the reporting rates. The accuracy and sharpness of forecasts improved substantially when these a priori distributions were used in models for prediction. For example, early forecasts of final epidemic size obtained without historical information were 3.3 times too high on average (range: 0.2 to 5.8) with respect to the eventual size, but were far closer (1.1 times the real value on average, range: 0.4 to 1.5) using information on past CHIKV epidemics in the same places. Likewise, the 97.5% upper bound for maximal incidence was 15.3 times (range: 2.0 to 63.1) the actual peak incidence, and became much sharper at 2.4 times (range: 1.3 to 3.9) the actual peak incidence with informative a priori distributions. Improvements were more limited for the date of peak incidence and the total duration of the epidemic. The framework can adapt to all forecasting models at the early stages of emerging Aedes-transmitted outbreaks.",2018 Jun 4,"['Riou, Julien', 'Poletto, Chiara', 'Boëlle, Pierre-Yves']",PLoS Negl Trop Dis,,,True
f2a4078a4441df3a53a2d719375da1c57bd93346,PMC,Sub-national variation in measles vaccine coverage and outbreak risk: a case study from a 2010 outbreak in Malawi,http://dx.doi.org/10.1186/s12889-018-5628-x,PMC6003196,29902976,CC BY,"BACKGROUND: Despite progress towards increasing global vaccination coverage, measles continues to be one of the leading, preventable causes of death among children worldwide. Whether and how to target sub-national areas for vaccination campaigns continues to remain a question. We analyzed three metrics for prioritizing target areas: vaccination coverage, susceptible birth cohort, and the effective reproductive ratio (R(E)) in the context of the 2010 measles epidemic in Malawi. METHODS: Using case-based surveillance data from the 2010 measles outbreak in Malawi, we estimated vaccination coverage from the proportion of cases reporting with a history of prior vaccination at the district and health facility catchment scale. Health facility catchments were defined as the set of locations closer to a given health facility than to any other. We combined these estimates with regional birth rates to estimate the size of the annual susceptible birth cohort. We also estimated the effective reproductive ratio, R(E), at the health facility polygon scale based on the observed rate of exponential increase of the epidemic. We combined these estimates to identify spatial regions that would be of high priority for supplemental vaccination activities. RESULTS: The estimated vaccination coverage across all districts was 84%, but ranged from 61 to 99%. We found that 8 districts and 354 health facility catchments had estimated vaccination coverage below 80%. Areas that had highest birth cohort size were frequently large urban centers that had high vaccination coverage. The estimated R(E) ranged between 1 and 2.56. The ranking of districts and health facility catchments as priority areas varied depending on the measure used. CONCLUSIONS: Each metric for prioritization may result in discrete target areas for vaccination campaigns; thus, there are tradeoffs to choosing one metric over another. However, in some cases, certain areas may be prioritized by all three metrics. These areas should be treated with particular concern. Furthermore, the spatial scale at which each metric is calculated impacts the resulting prioritization and should also be considered when prioritizing areas for vaccination campaigns. These methods may be used to allocate effort for prophylactic campaigns or to prioritize response for outbreak response vaccination.",2018 Jun 15,"['Kundrick, Avery', 'Huang, Zhuojie', 'Carran, Spencer', 'Kagoli, Matthew', 'Grais, Rebecca Freeman', 'Hurtado, Northan', 'Ferrari, Matthew']",BMC Public Health,,,True
dbf57f4f3e966f629f433d013c57a68c52a909b8,PMC,Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model,http://dx.doi.org/10.1038/s41598-018-27626-4,PMC6003913,29907804,CC BY,"The aim of the present study was to investigate long-term outcomes of the offspring in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) model and the effect of maternal molecular hydrogen (H(2)) administration. We have previously demonstrated in the MIA mouse model that maternal administration of H(2) attenuates oxidative damage and neuroinflammation, including induced pro-inflammatory cytokines and microglial activation, in the fetal brain. Short-term memory, sociability and social novelty, and sensorimotor gating were evaluated using the Y-maze, three-chamber, and prepulse inhibition (PPI) tests, respectively, at postnatal 3 or 4 weeks. The number of neurons and oligodendrocytes was also analyzed at postnatal 5 weeks by immunohistochemical analysis. Offspring of the LPS-exposed dams showed deficits in short-term memory and social interaction, following neuronal and oligodendrocytic loss in the amygdala and cortex. Maternal H(2) administration markedly attenuated these LPS-induced abnormalities. Moreover, we evaluated the effect of H(2) on LPS-induced astrocytic activation, both in vivo and in vitro. The number of activated astrocytes with hypertrophic morphology was increased in LPS-exposed offspring, but decreased in the offspring of H(2)-administered dams. In primary cultured astrocytes, LPS-induced pro-inflammatory cytokines were attenuated by H(2) administration. Overall, these findings indicate that maternal H(2) administration exerts neuroprotective effects and ameliorates MIA-induced neurodevelopmental deficits of offspring later in life.",2018 Jun 15,"['Imai, Kenji', 'Kotani, Tomomi', 'Tsuda, Hiroyuki', 'Nakano, Tomoko', 'Ushida, Takafumi', 'Iwase, Akira', 'Nagai, Taku', 'Toyokuni, Shinya', 'Suzumura, Akio', 'Kikkawa, Fumitaka']",Sci Rep,,,False
d603d8aa5b328d708683d754f224c1f9d170fc64,PMC,Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model,http://dx.doi.org/10.1038/s41598-018-27626-4,PMC6003913,29907804,CC BY,"The aim of the present study was to investigate long-term outcomes of the offspring in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) model and the effect of maternal molecular hydrogen (H(2)) administration. We have previously demonstrated in the MIA mouse model that maternal administration of H(2) attenuates oxidative damage and neuroinflammation, including induced pro-inflammatory cytokines and microglial activation, in the fetal brain. Short-term memory, sociability and social novelty, and sensorimotor gating were evaluated using the Y-maze, three-chamber, and prepulse inhibition (PPI) tests, respectively, at postnatal 3 or 4 weeks. The number of neurons and oligodendrocytes was also analyzed at postnatal 5 weeks by immunohistochemical analysis. Offspring of the LPS-exposed dams showed deficits in short-term memory and social interaction, following neuronal and oligodendrocytic loss in the amygdala and cortex. Maternal H(2) administration markedly attenuated these LPS-induced abnormalities. Moreover, we evaluated the effect of H(2) on LPS-induced astrocytic activation, both in vivo and in vitro. The number of activated astrocytes with hypertrophic morphology was increased in LPS-exposed offspring, but decreased in the offspring of H(2)-administered dams. In primary cultured astrocytes, LPS-induced pro-inflammatory cytokines were attenuated by H(2) administration. Overall, these findings indicate that maternal H(2) administration exerts neuroprotective effects and ameliorates MIA-induced neurodevelopmental deficits of offspring later in life.",2018 Jun 15,"['Imai, Kenji', 'Kotani, Tomomi', 'Tsuda, Hiroyuki', 'Nakano, Tomoko', 'Ushida, Takafumi', 'Iwase, Akira', 'Nagai, Taku', 'Toyokuni, Shinya', 'Suzumura, Akio', 'Kikkawa, Fumitaka']",Sci Rep,,,True
53408b1daf9132c89bebd23cdd7e417ad668b1ce,PMC,Seroprevalence and genotyping of avian infectious bronchitis virus detected from Iranian unvaccinated backyard chickens,,PMC6004632,29922421,CC BY,"BACKGROUND AND OBJECTIVES: Different epidemiological studies have found that backyard chickens are a reservoir for poultry diseases. Most backyard chicken flocks have a poor level of biosecurity, which increases the risk of spread of diseases. In recent years, the number of backyard chickens has been on the rise in Iran. However, the health status of backyard flocks is still poorly documented. Thus, this study aimed at examining the seroprevalence of antibodies against infectious bronchitis virus (IBV) and molecular surveillance and genotyping of IBV among backyard chickens (without vaccination history) in Mazandaran province, North of Iran, 2014. MATERIALS AND METHODS: A total of 460 blood samples of unvaccinated backyard chickens in the mentioned area were tested for antibodies against IBV using commercial ELISA. Also, cecal tonsils were collected from 75 chickens in the same area. Real time RT-PCR (for detection) and RT-PCR and sequencing spike gene were performed. RESULTS: The seropositivity rate was 54.5%. In addition, we detected 793/B, Variant 2, and QX in the backyard flocks and performed phylogenetic studies on them. The phylogenetic study revealed that the detected genotypes had high homology with IBV strains that were infected broilers, pullets, and layers in Iran. CONCLUSION: There is a need for continuous monitoring of IBV among avian species to complete the epidemiological map and work on the pathogenesis of Iranian IBV strains in Iranian backyard chickens.",2018 Feb,"['Shokri, Shima', 'Karimi, Vahid', 'Langeroudi, Arash Ghalyanchi', 'Marandi, Mehdi Vasfi', 'Hashamzadeh, Masoud', 'Zabihipetroudi, Taha', 'Najafi, Hamideh', 'Tehrani, Farshad']",Iran J Microbiol,,,True
6acfca277c3e484c1dead20fc58db53b179c33ab,PMC,Distinct Gene Profiles of Bone Marrow-Derived Macrophages and Microglia During Neurotropic Coronavirus-Induced Demyelination,http://dx.doi.org/10.3389/fimmu.2018.01325,PMC6004766,29942315,CC BY,"Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination and axonal loss. Demyelinating lesions are associated with infiltrating T lymphocytes, bone marrow-derived macrophages (BMDM), and activated resident microglia. Tissue damage is thought to be mediated by T cell produced cytokines and chemokines, which activate microglia and/or BMDM to both strip myelin and produce toxic factors, ultimately damaging axons and promoting disability. However, the relative contributions of BMDM and microglia to demyelinating pathology are unclear, as their identification in MS tissue is difficult due to similar morphology and indistinguishable surface markers when activated. The CD4 T cell-induced autoimmune murine model of MS, experimental autoimmune encephalitis (EAE), in which BMDM are essential for demyelination, has revealed pathogenic and repair-promoting phenotypes associated with BMDM and microglia, respectively. Using a murine model of demyelination induced by a gliatropic coronavirus, in which BMDM are redundant for demyelination, we herein characterize gene expression profiles of BMDM versus microglia associated with demyelination. While gene expression in CNS infiltrating BMDM was upregulated early following infection and subsequently sustained, microglia expressed a more dynamic gene profile with extensive mRNA upregulation coinciding with peak demyelination after viral control. This delayed microglia response comprised a highly pro-inflammatory and phagocytic profile. Furthermore, while BMDM exhibited a mixed phenotype of M1 and M2 markers, microglia repressed the vast majority of M2-markers. Overall, these data support a pro-inflammatory and pathogenic role of microglia temporally remote from viral control, whereas BMDM retained their gene expression profile independent of the changing environment. As demyelination is caused by multifactorial insults, our results highlight the plasticity of microglia in responding to distinct inflammatory settings, which may be relevant for MS pathogenesis.",2018 Jun 11,"['Savarin, Carine', 'Dutta, Ranjan', 'Bergmann, Cornelia C.']",Front Immunol,,,True
7fd909b06fcb46cf45b5d099741e4a86138ac6f4,PMC,Respiratory virus of severe pneumonia in South Korea: Prevalence and clinical implications,http://dx.doi.org/10.1371/journal.pone.0198902,PMC6005478,29912989,CC BY,"BACKGROUND: Severe viral pneumonia is associated with a high mortality rate. However, due to the vulnerability of critically ill patients, invasive diagnostic methods should be performed with caution in the intensive care unit (ICU). It would be helpful if the prevalence, risk factors, and clinical impact of virus detection are elucidated. METHODS: We evaluated patients with severe pneumonia between January 1(st) 2008 and December 31(st) 2015. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed for 8 respiratory viruses when viral pathogen could not be excluded as the origin of severe pneumonia. The baseline characteristics, laboratory results, microbiological findings, and clinical outcomes of the patients were analyzed. RESULTS: Of the 2,347 patients admitted to the medical ICU, 515 underwent RT-PCR for respiratory viruses, 69 of whom had positive results. The detection rate was higher during the winter, with a community onset, in patients with history of recent chemotherapy, and low platelet count. Additional bronchoscopic sampling along with upper respiratory specimen increased the yield of viral detection. Respiratory syncytial virus was the most common pathogen detected, while influenza A was the most common virus with bacterial coinfection. Respiratory virus detection led to changes in clinical management in one-third of the patients. CONCLUSIONS: The detection of viral pathogens in patients with severe pneumonia is not rare, and can be more common in certain group of patients. Invasive sampling for RT-PCR can be helpful, and such detection can lead to positive changes in clinical management.",2018 Jun 18,"['Kim, Hyung-Jun', 'Choi, Sun Mi', 'Lee, Jinwoo', 'Park, Young Sik', 'Lee, Chang-Hoon', 'Yim, Jae-Joon', 'Yoo, Chul-Gyu', 'Kim, Young Whan', 'Han, Sung Koo', 'Lee, Sang-Min']",PLoS One,,,True
936be67318582ec9f336d9ee616b194571cb09d4,PMC,PreDicta chip-based high resolution diagnosis of rhinovirus-induced wheeze,http://dx.doi.org/10.1038/s41467-018-04591-0,PMC6006174,29915220,CC BY,"Rhinovirus (RV) infections are major triggers of acute exacerbations of severe respiratory diseases such as pre-school wheeze, asthma and chronic obstructive pulmonary disease (COPD). The occurrence of numerous RV types is a major challenge for the identification of the culprit virus types and for the improvement of virus type-specific treatment strategies. Here, we develop a chip containing 130 different micro-arrayed RV proteins and peptides and demonstrate in a cohort of 120 pre-school children, most of whom had been hospitalized due to acute wheeze, that it is possible to determine the culprit RV species with a minute blood sample by serology. Importantly, we identify RV-A and RV-C species as giving rise to most severe respiratory symptoms. Thus, we have generated a chip for the serological identification of RV-induced respiratory illness which should be useful for the rational development of preventive and therapeutic strategies targeting the most important RV types.",2018 Jun 18,"['Niespodziana, Katarzyna', 'Stenberg-Hammar, Katarina', 'Megremis, Spyridon', 'Cabauatan, Clarissa R.', 'Napora-Wijata, Kamila', 'Vacal, Phyllis C.', 'Gallerano, Daniela', 'Lupinek, Christian', 'Ebner, Daniel', 'Schlederer, Thomas', 'Harwanegg, Christian', 'Söderhäll, Cilla', 'van Hage, Marianne', 'Hedlin, Gunilla', 'Papadopoulos, Nikolaos G.', 'Valenta, Rudolf']",Nat Commun,,,False
555af83e372e832fe50790f0ee8192298e6ffecd,PMC,PreDicta chip-based high resolution diagnosis of rhinovirus-induced wheeze,http://dx.doi.org/10.1038/s41467-018-04591-0,PMC6006174,29915220,CC BY,"Rhinovirus (RV) infections are major triggers of acute exacerbations of severe respiratory diseases such as pre-school wheeze, asthma and chronic obstructive pulmonary disease (COPD). The occurrence of numerous RV types is a major challenge for the identification of the culprit virus types and for the improvement of virus type-specific treatment strategies. Here, we develop a chip containing 130 different micro-arrayed RV proteins and peptides and demonstrate in a cohort of 120 pre-school children, most of whom had been hospitalized due to acute wheeze, that it is possible to determine the culprit RV species with a minute blood sample by serology. Importantly, we identify RV-A and RV-C species as giving rise to most severe respiratory symptoms. Thus, we have generated a chip for the serological identification of RV-induced respiratory illness which should be useful for the rational development of preventive and therapeutic strategies targeting the most important RV types.",2018 Jun 18,"['Niespodziana, Katarzyna', 'Stenberg-Hammar, Katarina', 'Megremis, Spyridon', 'Cabauatan, Clarissa R.', 'Napora-Wijata, Kamila', 'Vacal, Phyllis C.', 'Gallerano, Daniela', 'Lupinek, Christian', 'Ebner, Daniel', 'Schlederer, Thomas', 'Harwanegg, Christian', 'Söderhäll, Cilla', 'van Hage, Marianne', 'Hedlin, Gunilla', 'Papadopoulos, Nikolaos G.', 'Valenta, Rudolf']",Nat Commun,,,False
a6d78920011473fe481d4fc46e9ba4535332b87c,PMC,PreDicta chip-based high resolution diagnosis of rhinovirus-induced wheeze,http://dx.doi.org/10.1038/s41467-018-04591-0,PMC6006174,29915220,CC BY,"Rhinovirus (RV) infections are major triggers of acute exacerbations of severe respiratory diseases such as pre-school wheeze, asthma and chronic obstructive pulmonary disease (COPD). The occurrence of numerous RV types is a major challenge for the identification of the culprit virus types and for the improvement of virus type-specific treatment strategies. Here, we develop a chip containing 130 different micro-arrayed RV proteins and peptides and demonstrate in a cohort of 120 pre-school children, most of whom had been hospitalized due to acute wheeze, that it is possible to determine the culprit RV species with a minute blood sample by serology. Importantly, we identify RV-A and RV-C species as giving rise to most severe respiratory symptoms. Thus, we have generated a chip for the serological identification of RV-induced respiratory illness which should be useful for the rational development of preventive and therapeutic strategies targeting the most important RV types.",2018 Jun 18,"['Niespodziana, Katarzyna', 'Stenberg-Hammar, Katarina', 'Megremis, Spyridon', 'Cabauatan, Clarissa R.', 'Napora-Wijata, Kamila', 'Vacal, Phyllis C.', 'Gallerano, Daniela', 'Lupinek, Christian', 'Ebner, Daniel', 'Schlederer, Thomas', 'Harwanegg, Christian', 'Söderhäll, Cilla', 'van Hage, Marianne', 'Hedlin, Gunilla', 'Papadopoulos, Nikolaos G.', 'Valenta, Rudolf']",Nat Commun,,,True
b7430273f21b3a172f7f6e796636e376c2053fd8,PMC,Impact of TGEV infection on the pig small intestine,http://dx.doi.org/10.1186/s12985-018-1012-9,PMC6006930,29914507,CC BY,"BACKGROUND: Pig diarrhea causes high mortality and large economic losses in the swine industry. Transmissible gastroenteritis virus (TGEV) causes pig diarrhea, with 100% mortality in piglets less than 2 weeks old. No investigation has yet been made of the small intestine of piglets that survived infection by TGEV. METHODS: In this study, we evaluated the impact of TGEV infection on the small intestine of recovered pigs. RESULTS: Histological analyses showed that TGEV infection led to villi atrophy, and reduced villous height and crypt depth. The number of SIgA positive cells, CD3(+)T cells, and dendritic cells (DCs) in jejunum decreased after TGEV infection in vivo. In contrast, microfold cell (M cell) numbers and cell proliferation increased in infected pigs. TGEV infection also significantly enhanced the mRNA expression levels of cytokine IL-1β, IL-6, TNF-α, IL-10, and TGF-β. Additionally, lower gene copy numbers of Lactobacillus, and higher numbers of Enterobacteriaceae, were detected in mucosal scraping samples from TGEV-infected pigs. CONCLUSIONS: TGEV infection damages the small intestine, impairs immune functions, and increases pathogenic bacterial loading, all of which may facilitate secondary infections by other pathogens. These findings help quantify the impact of TGEV infection and clarify the pathogenic mechanisms underlying its effects in pigs.",2018 Jun 19,"['Xia, Lu', 'Yang, Yunhan', 'Wang, Jialu', 'Jing, Yuchao', 'Yang, Qian']",Virol J,,,True
6d073fc71e9b58f7d85ab4ae64aaeadf10d56ae4,PMC,IFIT3 and IFIT2/3 promote IFIT1-mediated translation inhibition by enhancing binding to non-self RNA,http://dx.doi.org/10.1093/nar/gky191,PMC6007307,29554348,CC BY,"Interferon-induced proteins with tetratricopeptide repeats (IFITs) are highly expressed during the cell-intrinsic immune response to viral infection. IFIT1 inhibits translation by binding directly to the 5′ end of foreign RNAs, particularly those with non-self cap structures, precluding the recruitment of the cap-binding eukaryotic translation initiation factor 4F and ribosome recruitment. The presence of IFIT1 imposes a requirement on viruses that replicate in the cytoplasm to maintain mechanisms to avoid its restrictive effects. Interaction of different IFIT family members is well described, but little is known of the molecular basis of IFIT association or its impact on function. Here, we reconstituted different complexes of IFIT1, IFIT2 and IFIT3 in vitro, which enabled us to reveal critical aspects of IFIT complex assembly. IFIT1 and IFIT3 interact via a YxxxL motif present in the C-terminus of each protein. IFIT2 and IFIT3 homodimers dissociate to form a more stable heterodimer that also associates with IFIT1. We show for the first time that IFIT3 stabilizes IFIT1 protein expression, promotes IFIT1 binding to a cap0 Zika virus reporter mRNA and enhances IFIT1 translation inhibition. This work reveals molecular aspects of IFIT interaction and provides an important missing link between IFIT assembly and function.",2018 Jun 1,"['Fleith, Renata C', 'Mears, Harriet V', 'Leong, Xin Yun', 'Sanford, Thomas J', 'Emmott, Edward', 'Graham, Stephen C', 'Mansur, Daniel S', 'Sweeney, Trevor R']",Nucleic Acids Res,,,True
01a6e57546ad10e21a2c8e5e0e7c201e40d51f06,PMC,IFIT3 and IFIT2/3 promote IFIT1-mediated translation inhibition by enhancing binding to non-self RNA,http://dx.doi.org/10.1093/nar/gky191,PMC6007307,29554348,CC BY,"Interferon-induced proteins with tetratricopeptide repeats (IFITs) are highly expressed during the cell-intrinsic immune response to viral infection. IFIT1 inhibits translation by binding directly to the 5′ end of foreign RNAs, particularly those with non-self cap structures, precluding the recruitment of the cap-binding eukaryotic translation initiation factor 4F and ribosome recruitment. The presence of IFIT1 imposes a requirement on viruses that replicate in the cytoplasm to maintain mechanisms to avoid its restrictive effects. Interaction of different IFIT family members is well described, but little is known of the molecular basis of IFIT association or its impact on function. Here, we reconstituted different complexes of IFIT1, IFIT2 and IFIT3 in vitro, which enabled us to reveal critical aspects of IFIT complex assembly. IFIT1 and IFIT3 interact via a YxxxL motif present in the C-terminus of each protein. IFIT2 and IFIT3 homodimers dissociate to form a more stable heterodimer that also associates with IFIT1. We show for the first time that IFIT3 stabilizes IFIT1 protein expression, promotes IFIT1 binding to a cap0 Zika virus reporter mRNA and enhances IFIT1 translation inhibition. This work reveals molecular aspects of IFIT interaction and provides an important missing link between IFIT assembly and function.",2018 Jun 1,"['Fleith, Renata C', 'Mears, Harriet V', 'Leong, Xin Yun', 'Sanford, Thomas J', 'Emmott, Edward', 'Graham, Stephen C', 'Mansur, Daniel S', 'Sweeney, Trevor R']",Nucleic Acids Res,,,False
d986c44da50830e309f5d89cd81595edf1f05200,PMC,Building a Multi-Institutional and Interdisciplinary Team to Develop a Zoonotic Tuberculosis Roadmap,http://dx.doi.org/10.3389/fpubh.2018.00167,PMC6008525,29951476,CC BY,"Tuberculosis (TB), as the major infectious disease in the world, has devastating consequences for not only humans, but also cattle and several wildlife species. This disease presents additional challenges to human and veterinary health authorities given the zoonotic nature of the pathogens responsible for the disease across species. One of the main public health challenges regarding zoonotic TB (ZTB) caused by Mycobacterium bovis is that the true incidence of this type of TB in humans is not known and is likely to be underestimated. To effectively address challenges posed by ZTB, an integrated One Health approach is needed. In this manuscript, we describe the rationale, major steps, timeline, stakeholders, and important events that led to the assembling of a true integrated multi-institutional and interdisciplinary team that accomplished the ambitious goal of developing a ZTB roadmap, published in October, 2017. It outlines key activities to address the global challenges regarding the prevention, surveillance, diagnosis, and treatment of ZTB. We discuss and emphasize the importance of integrated approaches to be able to accomplish the short (year 2020) and medium term (year 2025) goals outlined in the ZTB roadmap.",2018 Jun 12,"['Olea-Popelka, Francisco', 'Fujiwara, Paula I.']",Front Public Health,,,True
18d519cf1ea884ddf381067f0733c18d8ad94c7a,PMC,"ZIKV Infection Induces an Inflammatory Response but Fails to Activate Types I, II, and III IFN Response in Human PBMC",http://dx.doi.org/10.1155/2018/2450540,PMC6008743,29967565,CC BY,"The recent epidemic in the Americas caused by Zika virus (ZIKV), Asian lineage, spurred the research towards a better understanding of how ZIKV infection affects the host immune response. The aim of this study was to evaluate the effects of Asian and East African ZIKV strain infection on the induction of IFN and proinflammatory and Th2 cytokines in human PBMC. We reported a slight modulation of type II IFN in PBMC exposed to Asian strain, but not to African strain, and a complete lack of type I and III IFN induction by both strains, suggesting the ability of ZIKV to evade the IFN system not only inhibiting the antiviral IFN response but also IFN production. Moreover, we highlighted a polyfunctional immune activation only in PBMC exposed to Asian strain, due to the induction of an inflammatory profile (IL-6, IL-8) and of a Th9 (IL-9) response. Overall, our data show a different ability of the ZIKV Asian strain, with respect to the African strain, to activate host immune response that may have pathogenetic implications for virus spread in vivo, including mother-to-child transmission and induction of severe fetal complications, as birth defects and neurological disorders.",2018 Jun 3,"['Colavita, Francesca', 'Bordoni, Veronica', 'Caglioti, Claudia', 'Biava, Mirella', 'Castilletti, Concetta', 'Bordi, Licia', 'Quartu, Serena', 'Iannetta, Marco', 'Ippolito, Giuseppe', 'Agrati, Chiara', 'Capobianchi, Maria Rosaria', 'Lalle, Eleonora']",Mediators Inflamm,,,True
02d808df510466b74102dd922486bf922a5ed947,PMC,Evaluation of polyphenols from Broussonetia papyrifera as coronavirus protease inhibitors,http://dx.doi.org/10.1080/14756366.2016.1265519,PMC6010046,28112000,CC BY,"The current study was designed to assess the inhibitory activity of Broussonetia papyrifera-derived polyphenols against 3-chymotrypsin-like and papain-like coronavirus cysteine proteases. The isolated compounds were broussochalcone B (1), broussochalcone A (2), 4-hydroxyisolonchocarpin (3), papyriflavonol A (4), 3′-(3-methylbut-2-enyl)-3′,4,7-trihydroxyflavane (5), kazinol A (6), kazinol B (7), broussoflavan A (8), kazinol F (9), and kazinol J (10). All polyphenols were more potent against papain-like protease (PL(pro)) than against 3-chymotripsin-like protease (3CL(pro)); therefore, we investigated their structural features that were responsible for this selectivity. Compound 4 was the most potent inhibitor of PL(pro) with an IC(50) value of 3.7 μM. The active compounds displayed kinetic behaviors, and the binding constants of their interaction with PL(pro) were determined from surface plasmon resonance analysis. Our results suggest B. papyrifera constituents as promising candidates for development into potential anti-coronaviral agents.",2017 Jan 22,"['Park, Ji-Young', 'Yuk, Heung Joo', 'Ryu, Hyung Won', 'Lim, Su Hwan', 'Kim, Kyung Su', 'Park, Ki Hun', 'Ryu, Young Bae', 'Lee, Woo Song']",J Enzyme Inhib Med Chem,,,True
f0bb38fb7ea86c32fd7179e913988b19e577b0b8,PMC,Evaluation of polyphenols from Broussonetia papyrifera as coronavirus protease inhibitors,http://dx.doi.org/10.1080/14756366.2016.1265519,PMC6010046,28112000,CC BY,"The current study was designed to assess the inhibitory activity of Broussonetia papyrifera-derived polyphenols against 3-chymotrypsin-like and papain-like coronavirus cysteine proteases. The isolated compounds were broussochalcone B (1), broussochalcone A (2), 4-hydroxyisolonchocarpin (3), papyriflavonol A (4), 3′-(3-methylbut-2-enyl)-3′,4,7-trihydroxyflavane (5), kazinol A (6), kazinol B (7), broussoflavan A (8), kazinol F (9), and kazinol J (10). All polyphenols were more potent against papain-like protease (PL(pro)) than against 3-chymotripsin-like protease (3CL(pro)); therefore, we investigated their structural features that were responsible for this selectivity. Compound 4 was the most potent inhibitor of PL(pro) with an IC(50) value of 3.7 μM. The active compounds displayed kinetic behaviors, and the binding constants of their interaction with PL(pro) were determined from surface plasmon resonance analysis. Our results suggest B. papyrifera constituents as promising candidates for development into potential anti-coronaviral agents.",2017 Jan 22,"['Park, Ji-Young', 'Yuk, Heung Joo', 'Ryu, Hyung Won', 'Lim, Su Hwan', 'Kim, Kyung Su', 'Park, Ki Hun', 'Ryu, Young Bae', 'Lee, Woo Song']",J Enzyme Inhib Med Chem,,,False
c6981b83471474649ada35c45fe43e091aab4553,PMC,Anticipating epidemic transitions with imperfect data,http://dx.doi.org/10.1371/journal.pcbi.1006204,PMC6010299,29883444,CC BY,"Epidemic transitions are an important feature of infectious disease systems. As the transmissibility of a pathogen increases, the dynamics of disease spread shifts from limited stuttering chains of transmission to potentially large scale outbreaks. One proposed method to anticipate this transition are early-warning signals (EWS), summary statistics which undergo characteristic changes as the transition is approached. Although theoretically predicted, their mathematical basis does not take into account the nature of epidemiological data, which are typically aggregated into periodic case reports and subject to reporting error. The viability of EWS for epidemic transitions therefore remains uncertain. Here we demonstrate that most EWS can predict emergence even when calculated from imperfect data. We quantify performance using the area under the curve (AUC) statistic, a measure of how well an EWS distinguishes between numerical simulations of an emerging disease and one which is stationary. Values of the AUC statistic are compared across a range of different reporting scenarios. We find that different EWS respond to imperfect data differently. The mean, variance and first differenced variance all perform well unless reporting error is highly overdispersed. The autocorrelation, autocovariance and decay time perform well provided that the aggregation period of the data is larger than the serial interval and reporting error is not highly overdispersed. The coefficient of variation, skewness and kurtosis are found to be unreliable indicators of emergence. Overall, we find that seven of ten EWS considered perform well for most realistic reporting scenarios. We conclude that imperfect epidemiological data is not a barrier to using EWS for many potentially emerging diseases.",2018 Jun 8,"['Brett, Tobias S.', 'O’Dea, Eamon B.', 'Marty, Éric', 'Miller, Paige B.', 'Park, Andrew W.', 'Drake, John M.', 'Rohani, Pejman']",PLoS Comput Biol,,,True
41b659ac51b4f4596b414e93c5dd220b26386f34,PMC,"Avian influenza surveillance in domestic waterfowl and environment of live bird markets in Bangladesh, 2007–2012",http://dx.doi.org/10.1038/s41598-018-27515-w,PMC6010472,29925854,CC BY,"Avian influenza viruses, including highly pathogenic strains, pose severe economic, animal and public health concerns. We implemented live bird market surveillance in Bangladesh to identify the subtypes of avian influenza A viruses in domestic waterfowl and market environments. We collected waterfowl samples monthly from 4 rural sites from 2007 to 2012 and environmental samples from 4 rural and 16 urban sites from 2009 to 2012. Samples were tested through real-time RT-PCR, virus culture, and sequencing to detect and characterize avian influenza A viruses. Among 4,308 waterfowl tested, 191 (4.4%) were positive for avian influenza A virus, including 74 (1.9%) avian influenza A/H5 subtype. The majority (99%, n = 73) of the influenza A/H5-positive samples were from healthy appearing waterfowl. Multiple subtypes, including H1N1, H1N3, H3N2, H3N6, H3N8, H4N1, H4N2, H4N6, H5N1 (clades 2.2.2, 2.3.2.1a, 2.3.4.2), H5N2, H6N1, H7N9, H9N2, H11N2 and H11N3, H11N6 were detected in waterfowl and environmental samples. Environmental samples tested positive for influenza A viruses throughout the year. Avian influenza viruses, including H5N1 and H9N2 subtypes were also identified in backyard and small-scale raised poultry. Live bird markets could be high-risk sites for harboring the viruses and have the potential to infect naive birds and humans exposed to them.",2018 Jun 20,"['Khan, Salah Uddin', 'Gurley, Emily S.', 'Gerloff, Nancy', 'Rahman, Md Z.', 'Simpson, Natosha', 'Rahman, Mustafizur', 'Haider, Najmul', 'Chowdhury, Sukanta', 'Balish, Amanda', 'Zaman, Rashid Uz', 'Nasreen, Sharifa', 'Chandra Das, Bidhan', 'Azziz-Baumgartner, Eduardo', 'Sturm-Ramirez, Katharine', 'Davis, C. Todd', 'Donis, Ruben O.', 'Luby, Stephen P.']",Sci Rep,,,True
7b2ce72842bc40763d6f9696a8f4280d741cc5a3,PMC,"Avian influenza surveillance in domestic waterfowl and environment of live bird markets in Bangladesh, 2007–2012",http://dx.doi.org/10.1038/s41598-018-27515-w,PMC6010472,29925854,CC BY,"Avian influenza viruses, including highly pathogenic strains, pose severe economic, animal and public health concerns. We implemented live bird market surveillance in Bangladesh to identify the subtypes of avian influenza A viruses in domestic waterfowl and market environments. We collected waterfowl samples monthly from 4 rural sites from 2007 to 2012 and environmental samples from 4 rural and 16 urban sites from 2009 to 2012. Samples were tested through real-time RT-PCR, virus culture, and sequencing to detect and characterize avian influenza A viruses. Among 4,308 waterfowl tested, 191 (4.4%) were positive for avian influenza A virus, including 74 (1.9%) avian influenza A/H5 subtype. The majority (99%, n = 73) of the influenza A/H5-positive samples were from healthy appearing waterfowl. Multiple subtypes, including H1N1, H1N3, H3N2, H3N6, H3N8, H4N1, H4N2, H4N6, H5N1 (clades 2.2.2, 2.3.2.1a, 2.3.4.2), H5N2, H6N1, H7N9, H9N2, H11N2 and H11N3, H11N6 were detected in waterfowl and environmental samples. Environmental samples tested positive for influenza A viruses throughout the year. Avian influenza viruses, including H5N1 and H9N2 subtypes were also identified in backyard and small-scale raised poultry. Live bird markets could be high-risk sites for harboring the viruses and have the potential to infect naive birds and humans exposed to them.",2018 Jun 20,"['Khan, Salah Uddin', 'Gurley, Emily S.', 'Gerloff, Nancy', 'Rahman, Md Z.', 'Simpson, Natosha', 'Rahman, Mustafizur', 'Haider, Najmul', 'Chowdhury, Sukanta', 'Balish, Amanda', 'Zaman, Rashid Uz', 'Nasreen, Sharifa', 'Chandra Das, Bidhan', 'Azziz-Baumgartner, Eduardo', 'Sturm-Ramirez, Katharine', 'Davis, C. Todd', 'Donis, Ruben O.', 'Luby, Stephen P.']",Sci Rep,,,True
d9cd10250bab75a881cb23146ea83b8dee7bb302,PMC,Bacterial RecA Protein Promotes Adenoviral Recombination during In Vitro Infection,http://dx.doi.org/10.1128/mSphere.00105-18,PMC6010623,29925671,CC BY,"Adenovirus infections in humans are common and sometimes lethal. Adenovirus-derived vectors are also commonly chosen for gene therapy in human clinical trials. We have shown in previous work that homologous recombination between adenoviral genomes of human adenovirus species D (HAdV-D), the largest and fastest growing HAdV species, is responsible for the rapid evolution of this species. Because adenovirus infection initiates in mucosal epithelia, particularly at the gastrointestinal, respiratory, genitourinary, and ocular surfaces, we sought to determine a possible role for mucosal microbiota in adenovirus genome diversity. By analysis of known recombination hot spots across 38 human adenovirus genomes in species D (HAdV-D), we identified nucleotide sequence motifs similar to bacterial Chi sequences, which facilitate homologous recombination in the presence of bacterial Rec enzymes. These motifs, referred to here as Chi(AD), were identified immediately 5′ to the sequence encoding penton base hypervariable loop 2, which expresses the arginine-glycine-aspartate moiety critical to adenoviral cellular entry. Coinfection with two HAdV-Ds in the presence of an Escherichia coli lysate increased recombination; this was blocked in a RecA mutant strain, E. coli DH5α, or upon RecA depletion. Recombination increased in the presence of E. coli lysate despite a general reduction in viral replication. RecA colocalized with viral DNA in HAdV-D-infected cell nuclei and was shown to bind specifically to Chi(AD) sequences. These results indicate that adenoviruses may repurpose bacterial recombination machinery, a sharing of evolutionary mechanisms across a diverse microbiota, and unique example of viral commensalism. IMPORTANCE Adenoviruses are common human mucosal pathogens of the gastrointestinal, respiratory, and genitourinary tracts and ocular surface. Here, we report finding Chi-like sequences in adenovirus recombination hot spots. Adenovirus coinfection in the presence of bacterial RecA protein facilitated homologous recombination between viruses. Genetic recombination led to evolution of an important external feature on the adenoviral capsid, namely, the penton base protein hypervariable loop 2, which contains the arginine-glycine-aspartic acid motif critical to viral internalization. We speculate that free Rec proteins present in gastrointestinal secretions upon bacterial cell death facilitate the evolution of human adenoviruses through homologous recombination, an example of viral commensalism and the complexity of virus-host interactions, including regional microbiota.",2018 Jun 20,"['Lee, Jeong Yoon', 'Lee, Ji Sun', 'Materne, Emma C.', 'Rajala, Rahul', 'Ismail, Ashrafali M.', 'Seto, Donald', 'Dyer, David W.', 'Rajaiya, Jaya', 'Chodosh, James']",mSphere,,,True
8b8b853eb697f46aa29194195c83a003a2d8fe36,PMC,Bacterial RecA Protein Promotes Adenoviral Recombination during In Vitro Infection,http://dx.doi.org/10.1128/mSphere.00105-18,PMC6010623,29925671,CC BY,"Adenovirus infections in humans are common and sometimes lethal. Adenovirus-derived vectors are also commonly chosen for gene therapy in human clinical trials. We have shown in previous work that homologous recombination between adenoviral genomes of human adenovirus species D (HAdV-D), the largest and fastest growing HAdV species, is responsible for the rapid evolution of this species. Because adenovirus infection initiates in mucosal epithelia, particularly at the gastrointestinal, respiratory, genitourinary, and ocular surfaces, we sought to determine a possible role for mucosal microbiota in adenovirus genome diversity. By analysis of known recombination hot spots across 38 human adenovirus genomes in species D (HAdV-D), we identified nucleotide sequence motifs similar to bacterial Chi sequences, which facilitate homologous recombination in the presence of bacterial Rec enzymes. These motifs, referred to here as Chi(AD), were identified immediately 5′ to the sequence encoding penton base hypervariable loop 2, which expresses the arginine-glycine-aspartate moiety critical to adenoviral cellular entry. Coinfection with two HAdV-Ds in the presence of an Escherichia coli lysate increased recombination; this was blocked in a RecA mutant strain, E. coli DH5α, or upon RecA depletion. Recombination increased in the presence of E. coli lysate despite a general reduction in viral replication. RecA colocalized with viral DNA in HAdV-D-infected cell nuclei and was shown to bind specifically to Chi(AD) sequences. These results indicate that adenoviruses may repurpose bacterial recombination machinery, a sharing of evolutionary mechanisms across a diverse microbiota, and unique example of viral commensalism. IMPORTANCE Adenoviruses are common human mucosal pathogens of the gastrointestinal, respiratory, and genitourinary tracts and ocular surface. Here, we report finding Chi-like sequences in adenovirus recombination hot spots. Adenovirus coinfection in the presence of bacterial RecA protein facilitated homologous recombination between viruses. Genetic recombination led to evolution of an important external feature on the adenoviral capsid, namely, the penton base protein hypervariable loop 2, which contains the arginine-glycine-aspartic acid motif critical to viral internalization. We speculate that free Rec proteins present in gastrointestinal secretions upon bacterial cell death facilitate the evolution of human adenoviruses through homologous recombination, an example of viral commensalism and the complexity of virus-host interactions, including regional microbiota.",2018 Jun 20,"['Lee, Jeong Yoon', 'Lee, Ji Sun', 'Materne, Emma C.', 'Rajala, Rahul', 'Ismail, Ashrafali M.', 'Seto, Donald', 'Dyer, David W.', 'Rajaiya, Jaya', 'Chodosh, James']",mSphere,,,False
3ef64680e9ff547fef5377039092261470f5fe92,PMC,Bacterial RecA Protein Promotes Adenoviral Recombination during In Vitro Infection,http://dx.doi.org/10.1128/mSphere.00105-18,PMC6010623,29925671,CC BY,"Adenovirus infections in humans are common and sometimes lethal. Adenovirus-derived vectors are also commonly chosen for gene therapy in human clinical trials. We have shown in previous work that homologous recombination between adenoviral genomes of human adenovirus species D (HAdV-D), the largest and fastest growing HAdV species, is responsible for the rapid evolution of this species. Because adenovirus infection initiates in mucosal epithelia, particularly at the gastrointestinal, respiratory, genitourinary, and ocular surfaces, we sought to determine a possible role for mucosal microbiota in adenovirus genome diversity. By analysis of known recombination hot spots across 38 human adenovirus genomes in species D (HAdV-D), we identified nucleotide sequence motifs similar to bacterial Chi sequences, which facilitate homologous recombination in the presence of bacterial Rec enzymes. These motifs, referred to here as Chi(AD), were identified immediately 5′ to the sequence encoding penton base hypervariable loop 2, which expresses the arginine-glycine-aspartate moiety critical to adenoviral cellular entry. Coinfection with two HAdV-Ds in the presence of an Escherichia coli lysate increased recombination; this was blocked in a RecA mutant strain, E. coli DH5α, or upon RecA depletion. Recombination increased in the presence of E. coli lysate despite a general reduction in viral replication. RecA colocalized with viral DNA in HAdV-D-infected cell nuclei and was shown to bind specifically to Chi(AD) sequences. These results indicate that adenoviruses may repurpose bacterial recombination machinery, a sharing of evolutionary mechanisms across a diverse microbiota, and unique example of viral commensalism. IMPORTANCE Adenoviruses are common human mucosal pathogens of the gastrointestinal, respiratory, and genitourinary tracts and ocular surface. Here, we report finding Chi-like sequences in adenovirus recombination hot spots. Adenovirus coinfection in the presence of bacterial RecA protein facilitated homologous recombination between viruses. Genetic recombination led to evolution of an important external feature on the adenoviral capsid, namely, the penton base protein hypervariable loop 2, which contains the arginine-glycine-aspartic acid motif critical to viral internalization. We speculate that free Rec proteins present in gastrointestinal secretions upon bacterial cell death facilitate the evolution of human adenoviruses through homologous recombination, an example of viral commensalism and the complexity of virus-host interactions, including regional microbiota.",2018 Jun 20,"['Lee, Jeong Yoon', 'Lee, Ji Sun', 'Materne, Emma C.', 'Rajala, Rahul', 'Ismail, Ashrafali M.', 'Seto, Donald', 'Dyer, David W.', 'Rajaiya, Jaya', 'Chodosh, James']",mSphere,,,False
9f2daf7a7a5b4a936c74c3e26a669d93af6ef443,PMC,Bacterial RecA Protein Promotes Adenoviral Recombination during In Vitro Infection,http://dx.doi.org/10.1128/mSphere.00105-18,PMC6010623,29925671,CC BY,"Adenovirus infections in humans are common and sometimes lethal. Adenovirus-derived vectors are also commonly chosen for gene therapy in human clinical trials. We have shown in previous work that homologous recombination between adenoviral genomes of human adenovirus species D (HAdV-D), the largest and fastest growing HAdV species, is responsible for the rapid evolution of this species. Because adenovirus infection initiates in mucosal epithelia, particularly at the gastrointestinal, respiratory, genitourinary, and ocular surfaces, we sought to determine a possible role for mucosal microbiota in adenovirus genome diversity. By analysis of known recombination hot spots across 38 human adenovirus genomes in species D (HAdV-D), we identified nucleotide sequence motifs similar to bacterial Chi sequences, which facilitate homologous recombination in the presence of bacterial Rec enzymes. These motifs, referred to here as Chi(AD), were identified immediately 5′ to the sequence encoding penton base hypervariable loop 2, which expresses the arginine-glycine-aspartate moiety critical to adenoviral cellular entry. Coinfection with two HAdV-Ds in the presence of an Escherichia coli lysate increased recombination; this was blocked in a RecA mutant strain, E. coli DH5α, or upon RecA depletion. Recombination increased in the presence of E. coli lysate despite a general reduction in viral replication. RecA colocalized with viral DNA in HAdV-D-infected cell nuclei and was shown to bind specifically to Chi(AD) sequences. These results indicate that adenoviruses may repurpose bacterial recombination machinery, a sharing of evolutionary mechanisms across a diverse microbiota, and unique example of viral commensalism. IMPORTANCE Adenoviruses are common human mucosal pathogens of the gastrointestinal, respiratory, and genitourinary tracts and ocular surface. Here, we report finding Chi-like sequences in adenovirus recombination hot spots. Adenovirus coinfection in the presence of bacterial RecA protein facilitated homologous recombination between viruses. Genetic recombination led to evolution of an important external feature on the adenoviral capsid, namely, the penton base protein hypervariable loop 2, which contains the arginine-glycine-aspartic acid motif critical to viral internalization. We speculate that free Rec proteins present in gastrointestinal secretions upon bacterial cell death facilitate the evolution of human adenoviruses through homologous recombination, an example of viral commensalism and the complexity of virus-host interactions, including regional microbiota.",2018 Jun 20,"['Lee, Jeong Yoon', 'Lee, Ji Sun', 'Materne, Emma C.', 'Rajala, Rahul', 'Ismail, Ashrafali M.', 'Seto, Donald', 'Dyer, David W.', 'Rajaiya, Jaya', 'Chodosh, James']",mSphere,,,False
5833bf10952ff4fa3eab3df99b0efdf9e033f961,PMC,Bacterial RecA Protein Promotes Adenoviral Recombination during In Vitro Infection,http://dx.doi.org/10.1128/mSphere.00105-18,PMC6010623,29925671,CC BY,"Adenovirus infections in humans are common and sometimes lethal. Adenovirus-derived vectors are also commonly chosen for gene therapy in human clinical trials. We have shown in previous work that homologous recombination between adenoviral genomes of human adenovirus species D (HAdV-D), the largest and fastest growing HAdV species, is responsible for the rapid evolution of this species. Because adenovirus infection initiates in mucosal epithelia, particularly at the gastrointestinal, respiratory, genitourinary, and ocular surfaces, we sought to determine a possible role for mucosal microbiota in adenovirus genome diversity. By analysis of known recombination hot spots across 38 human adenovirus genomes in species D (HAdV-D), we identified nucleotide sequence motifs similar to bacterial Chi sequences, which facilitate homologous recombination in the presence of bacterial Rec enzymes. These motifs, referred to here as Chi(AD), were identified immediately 5′ to the sequence encoding penton base hypervariable loop 2, which expresses the arginine-glycine-aspartate moiety critical to adenoviral cellular entry. Coinfection with two HAdV-Ds in the presence of an Escherichia coli lysate increased recombination; this was blocked in a RecA mutant strain, E. coli DH5α, or upon RecA depletion. Recombination increased in the presence of E. coli lysate despite a general reduction in viral replication. RecA colocalized with viral DNA in HAdV-D-infected cell nuclei and was shown to bind specifically to Chi(AD) sequences. These results indicate that adenoviruses may repurpose bacterial recombination machinery, a sharing of evolutionary mechanisms across a diverse microbiota, and unique example of viral commensalism. IMPORTANCE Adenoviruses are common human mucosal pathogens of the gastrointestinal, respiratory, and genitourinary tracts and ocular surface. Here, we report finding Chi-like sequences in adenovirus recombination hot spots. Adenovirus coinfection in the presence of bacterial RecA protein facilitated homologous recombination between viruses. Genetic recombination led to evolution of an important external feature on the adenoviral capsid, namely, the penton base protein hypervariable loop 2, which contains the arginine-glycine-aspartic acid motif critical to viral internalization. We speculate that free Rec proteins present in gastrointestinal secretions upon bacterial cell death facilitate the evolution of human adenoviruses through homologous recombination, an example of viral commensalism and the complexity of virus-host interactions, including regional microbiota.",2018 Jun 20,"['Lee, Jeong Yoon', 'Lee, Ji Sun', 'Materne, Emma C.', 'Rajala, Rahul', 'Ismail, Ashrafali M.', 'Seto, Donald', 'Dyer, David W.', 'Rajaiya, Jaya', 'Chodosh, James']",mSphere,,,False
2f2921851e825705103320bf3d61f9d76e4c6b45,PMC,Aerosol Sampling in a Hospital Emergency Room Setting: A Complementary Surveillance Method for the Detection of Respiratory Viruses,http://dx.doi.org/10.3389/fpubh.2018.00174,PMC6011129,29963543,CC BY,"This study aimed to evaluate environmental air sampling as an alternative form of active surveillance for respiratory pathogens in clinical settings. Samples were collected from three locations in the Emergency Department at Duke University Hospital Systems from October 2017 to March 2018. Of the 44 samples collected, 12 were positive for known respiratory pathogens including influenza A, influenza D, and adenovirus. Results suggest bioaerosol sampling may serve as a complement to active surveillance in clinical settings. Additionally, since respiratory viruses were detected in aerosol samples, our results suggest that hospital infection control measures, including the use of N95 respirators, could be used to limit the spread of infectious viruses in the air.",2018 Jun 14,"['Choi, Jessica Y.', 'Zemke, Juliana', 'Philo, Sarah E.', 'Bailey, Emily S.', 'Yondon, Myagmarsukh', 'Gray, Gregory C.']",Front Public Health,,,True
d676bec86eb1a354cfa5370b98dcf1417c75a729,PMC,Bat Astrovirus in Mozambique,http://dx.doi.org/10.1186/s12985-018-1011-x,PMC6011250,29925396,CC BY,"Astroviruses (AstVs) are responsible for infection of a large diversity of mammalian and avian species, including bats, aquatic birds, livestock and humans. We investigated AstVs circulation in bats in Mozambique and Mayotte, a small island in the Comoros Archipelago located between east Africa and Madagascar. Biological material was collected from 338 bats and tested for the presence of the AstV RNA-dependent RNA-polymerase gene with a pan-AstV semi-nested polymerase chain reaction assay. None of the 79 samples obtained from Mayotte bats (Pteropus seychellensis comorensis and Chaerephon pusillus) tested positive; however, 20.1% of bats sampled in Mozambique shed AstVs at the time of sampling and significant interspecific variation in the proportion of positive bats was detected. Many AstVs sequences obtained from a given bat species clustered in different phylogenetic lineages, while others seem to reflect some level of host-virus association, but also with AstVs previously reported from Malagasy bats. Our findings support active circulation of a large diversity of AstVs in bats in the western Indian Ocean islands, including the southeastern African coast, and highlight the need for more detailed assessment of its risk of zoonotic transmission to human populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1011-x) contains supplementary material, which is available to authorized users.",2018 Jun 20,"['Hoarau, Flora', 'Le Minter, Gildas', 'Joffrin, Léa', 'Schoeman, M. Corrie', 'Lagadec, Erwan', 'Ramasindrazana, Beza', 'Dos Santos, Andréa', 'Goodman, Steven M.', 'Gudo, Eduardo S.', 'Mavingui, Patrick', 'Lebarbenchon, Camille']",Virol J,,,False
872b314b2512ccf6e934ab4e07358b85dcef3040,PMC,Bat Astrovirus in Mozambique,http://dx.doi.org/10.1186/s12985-018-1011-x,PMC6011250,29925396,CC BY,"Astroviruses (AstVs) are responsible for infection of a large diversity of mammalian and avian species, including bats, aquatic birds, livestock and humans. We investigated AstVs circulation in bats in Mozambique and Mayotte, a small island in the Comoros Archipelago located between east Africa and Madagascar. Biological material was collected from 338 bats and tested for the presence of the AstV RNA-dependent RNA-polymerase gene with a pan-AstV semi-nested polymerase chain reaction assay. None of the 79 samples obtained from Mayotte bats (Pteropus seychellensis comorensis and Chaerephon pusillus) tested positive; however, 20.1% of bats sampled in Mozambique shed AstVs at the time of sampling and significant interspecific variation in the proportion of positive bats was detected. Many AstVs sequences obtained from a given bat species clustered in different phylogenetic lineages, while others seem to reflect some level of host-virus association, but also with AstVs previously reported from Malagasy bats. Our findings support active circulation of a large diversity of AstVs in bats in the western Indian Ocean islands, including the southeastern African coast, and highlight the need for more detailed assessment of its risk of zoonotic transmission to human populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1011-x) contains supplementary material, which is available to authorized users.",2018 Jun 20,"['Hoarau, Flora', 'Le Minter, Gildas', 'Joffrin, Léa', 'Schoeman, M. Corrie', 'Lagadec, Erwan', 'Ramasindrazana, Beza', 'Dos Santos, Andréa', 'Goodman, Steven M.', 'Gudo, Eduardo S.', 'Mavingui, Patrick', 'Lebarbenchon, Camille']",Virol J,,,True
ba2d3601f5ae3bb5964c8515431abe352bad9437,PMC,"The association between temperature, rainfall and humidity with common climate-sensitive infectious diseases in Bangladesh",http://dx.doi.org/10.1371/journal.pone.0199579,PMC6013221,29928056,CC BY,"Bangladesh is one of the world’s most vulnerable countries for climate change. This observational study examined the association of temperature, humidity and rainfall with six common climate-sensitive infectious diseases in adults (malaria, diarrheal disease, enteric fever, encephalitis, pneumonia and bacterial meningitis) in northeastern Bangladesh. Subjects admitted to the adult medicine ward of a tertiary referral hospital in Sylhet, Bangladesh from 2008 to 2012 with a diagnosis of one of the six chosen climate-sensitive infectious diseases were enrolled in the study. Climate-related data were collected from the Bangladesh Meteorological Institute. Disease incidence was then analyzed against mean temperature, humidity and average rainfall for the Sylhet region. Statistical significance was determined using Mann-Whitney test, Chi-square test and ANOVA testing. 5033 patients were enrolled (58% male, 42% female, ratio 1.3:1). All six diseases showed highly significant (p = 0.01) rises in incidence between the study years 2008 (540 cases) and 2012 (1330 cases), compared with no significant rise in overall all-cause hospital admissions in the same period (p = 0.19). The highest number of malaria (135), diarrhea (266) and pneumonia (371) cases occurred during the rainy season. On the other hand, the maximum number of enteric fever (408), encephalitis (183) and meningitis (151) cases occurred during autumn, which follows the rainy season. A positive (P = 0.01) correlation was observed between increased temperature and the incidence of malaria, enteric fever and diarrhea, and a negative correlation with encephalitis, meningitis and pneumonia. Higher humidity correlated (P = 0.01) with a higher number of cases of malaria and diarrhea, but inversely correlated with meningitis and encephalitis. Higher incidences of encephalitis and meningitis occurred while there was low rainfall. Incidences of diarrhea, malaria and enteric fever, increased with rainfall, and then gradually decreased. The findings support a relationship between weather patterns and disease incidence, and provide essential baseline data for future large prospective studies.",2018 Jun 21,"['Chowdhury, Fazle Rabbi', 'Ibrahim, Quazi Shihab Uddin', 'Bari, Md. Shafiqul', 'Alam, M. M. Jahangir', 'Dunachie, Susanna J.', 'Rodriguez-Morales, Alfonso J.', 'Patwary, Md. Ismail']",PLoS One,,,True
1cc120441add6c07cd8bdef91b2b66129fbba27c,PMC,"The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics",http://dx.doi.org/10.1186/s12931-018-0784-1,PMC6013893,29929556,CC BY,"The Human Viral Challenge (HVC) model has, for many decades, helped in the understanding of respiratory viruses and their role in disease pathogenesis. In a controlled setting using small numbers of volunteers removed from community exposure to other infections, this experimental model enables proof of concept work to be undertaken on novel therapeutics, including vaccines, immunomodulators and antivirals, as well as new diagnostics. Crucially, unlike conventional phase 1 studies, challenge studies include evaluable efficacy endpoints that then guide decisions on how to optimise subsequent field studies, as recommended by the FDA and thus licensing studies that follow. Such a strategy optimises the benefit of the studies and identifies possible threats early on, minimising the risk to subsequent volunteers but also maximising the benefit of scarce resources available to the research group investing in the research. Inspired by the principles of the 3Rs (Replacement, Reduction and Refinement) now commonly applied in the preclinical phase, HVC studies allow refinement and reduction of the subsequent development phase, accelerating progress towards further statistically powered phase 2b studies. The breadth of data generated from challenge studies allows for exploration of a wide range of variables and endpoints that can then be taken through to pivotal phase 3 studies. We describe the disease burden for acute respiratory viral infections for which current conventional development strategies have failed to produce therapeutics that meet clinical need. The Authors describe the HVC model’s utility in increasing scientific understanding and in progressing promising therapeutics through development. The contribution of the model to the elucidation of the virus-host interaction, both regarding viral pathogenicity and the body’s immunological response is discussed, along with its utility to assist in the development of novel diagnostics. Future applications of the model are also explored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-018-0784-1) contains supplementary material, which is available to authorized users.",2018 Jun 22,"['Lambkin-Williams, Rob', 'Noulin, Nicolas', 'Mann, Alex', 'Catchpole, Andrew', 'Gilbert, Anthony S.']",Respir Res,,,False
f13c88733ea45be9e923a282dfd42f8c277c187c,PMC,"The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics",http://dx.doi.org/10.1186/s12931-018-0784-1,PMC6013893,29929556,CC BY,"The Human Viral Challenge (HVC) model has, for many decades, helped in the understanding of respiratory viruses and their role in disease pathogenesis. In a controlled setting using small numbers of volunteers removed from community exposure to other infections, this experimental model enables proof of concept work to be undertaken on novel therapeutics, including vaccines, immunomodulators and antivirals, as well as new diagnostics. Crucially, unlike conventional phase 1 studies, challenge studies include evaluable efficacy endpoints that then guide decisions on how to optimise subsequent field studies, as recommended by the FDA and thus licensing studies that follow. Such a strategy optimises the benefit of the studies and identifies possible threats early on, minimising the risk to subsequent volunteers but also maximising the benefit of scarce resources available to the research group investing in the research. Inspired by the principles of the 3Rs (Replacement, Reduction and Refinement) now commonly applied in the preclinical phase, HVC studies allow refinement and reduction of the subsequent development phase, accelerating progress towards further statistically powered phase 2b studies. The breadth of data generated from challenge studies allows for exploration of a wide range of variables and endpoints that can then be taken through to pivotal phase 3 studies. We describe the disease burden for acute respiratory viral infections for which current conventional development strategies have failed to produce therapeutics that meet clinical need. The Authors describe the HVC model’s utility in increasing scientific understanding and in progressing promising therapeutics through development. The contribution of the model to the elucidation of the virus-host interaction, both regarding viral pathogenicity and the body’s immunological response is discussed, along with its utility to assist in the development of novel diagnostics. Future applications of the model are also explored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-018-0784-1) contains supplementary material, which is available to authorized users.",2018 Jun 22,"['Lambkin-Williams, Rob', 'Noulin, Nicolas', 'Mann, Alex', 'Catchpole, Andrew', 'Gilbert, Anthony S.']",Respir Res,,,True
28af8fb783b6180c247285955b5e48df75947819,PMC,Meditation or exercise for preventing acute respiratory infection (MEPARI-2): A randomized controlled trial,http://dx.doi.org/10.1371/journal.pone.0197778,PMC6014660,29933369,CC BY,"BACKGROUND: Practice of meditation or exercise may enhance health to protect against acute infectious illness. OBJECTIVE: To assess preventive effects of meditation and exercise on acute respiratory infection (ARI) illness. DESIGN: Randomized controlled prevention trial with three parallel groups. SETTING: Madison, Wisconsin, USA. PARTICIPANTS: Community-recruited adults who did not regularly exercise or meditate. METHODS: 1) 8-week behavioral training in mindfulness-based stress reduction (MBSR); 2) matched 8-week training in moderate intensity sustained exercise (EX); or 3) observational waitlist control. Training classes occurred in September and October, with weekly ARI surveillance through May. Incidence, duration, and area-under-curve ARI global severity were measured using daily reports on the WURSS-24 during ARI illness. Viruses were identified multiplex PCR. Absenteeism, health care utilization, and psychosocial health self-report assessments were also employed. RESULTS: Of 413 participants randomized, 390 completed the trial. In the MBSR group, 74 experienced 112 ARI episodes with 1045 days of ARI illness. Among exercisers, 84 had 120 episodes totaling 1010 illness days. Eighty-two of the controls had 134 episodes with 1210 days of ARI illness. Mean global severity was 315 for MBSR (95% confidence interval 244, 386), 256 (193, 318) for EX, and 336 (268, 403) for controls. A prespecified multivariate zero-inflated regression model suggested reduced incidence for MBSR (p = 0.036) and lower global severity for EX (p = 0.042), compared to control, not quite attaining the p<0.025 prespecified cut-off for null hypothesis rejection. There were 73 ARI-related missed-work days and 22 ARI-related health care visits in the MBSR group, 82 days and 21 visits for exercisers, and 105 days and 24 visits among controls. Viruses were identified in 63 ARI episodes in the MBSR group, compared to 64 for EX and 72 for control. Statistically significant (p<0.05) improvements in general mental health, self-efficacy, mindful attention, sleep quality, perceived stress, and depressive symptoms were observed in the MBSR and/or EX groups, compared to control. CONCLUSIONS: Training in mindfulness meditation or exercise may help protect against ARI illness. LIMITATIONS: This trial was likely underpowered. TRIAL REGISTRATION: Clinicaltrials.gov NCT01654289",2018 Jun 22,"['Barrett, Bruce', 'Hayney, Mary S.', 'Muller, Daniel', 'Rakel, David', 'Brown, Roger', 'Zgierska, Aleksandra E.', 'Barlow, Shari', 'Hayer, Supriya', 'Barnet, Jodi H.', 'Torres, Elisa R.', 'Coe, Christopher L.']",PLoS One,,,True
98fccc3bc0b7e0a87e16695a754b2105aa2ffbb6,PMC,Meditation or exercise for preventing acute respiratory infection (MEPARI-2): A randomized controlled trial,http://dx.doi.org/10.1371/journal.pone.0197778,PMC6014660,29933369,CC BY,"BACKGROUND: Practice of meditation or exercise may enhance health to protect against acute infectious illness. OBJECTIVE: To assess preventive effects of meditation and exercise on acute respiratory infection (ARI) illness. DESIGN: Randomized controlled prevention trial with three parallel groups. SETTING: Madison, Wisconsin, USA. PARTICIPANTS: Community-recruited adults who did not regularly exercise or meditate. METHODS: 1) 8-week behavioral training in mindfulness-based stress reduction (MBSR); 2) matched 8-week training in moderate intensity sustained exercise (EX); or 3) observational waitlist control. Training classes occurred in September and October, with weekly ARI surveillance through May. Incidence, duration, and area-under-curve ARI global severity were measured using daily reports on the WURSS-24 during ARI illness. Viruses were identified multiplex PCR. Absenteeism, health care utilization, and psychosocial health self-report assessments were also employed. RESULTS: Of 413 participants randomized, 390 completed the trial. In the MBSR group, 74 experienced 112 ARI episodes with 1045 days of ARI illness. Among exercisers, 84 had 120 episodes totaling 1010 illness days. Eighty-two of the controls had 134 episodes with 1210 days of ARI illness. Mean global severity was 315 for MBSR (95% confidence interval 244, 386), 256 (193, 318) for EX, and 336 (268, 403) for controls. A prespecified multivariate zero-inflated regression model suggested reduced incidence for MBSR (p = 0.036) and lower global severity for EX (p = 0.042), compared to control, not quite attaining the p<0.025 prespecified cut-off for null hypothesis rejection. There were 73 ARI-related missed-work days and 22 ARI-related health care visits in the MBSR group, 82 days and 21 visits for exercisers, and 105 days and 24 visits among controls. Viruses were identified in 63 ARI episodes in the MBSR group, compared to 64 for EX and 72 for control. Statistically significant (p<0.05) improvements in general mental health, self-efficacy, mindful attention, sleep quality, perceived stress, and depressive symptoms were observed in the MBSR and/or EX groups, compared to control. CONCLUSIONS: Training in mindfulness meditation or exercise may help protect against ARI illness. LIMITATIONS: This trial was likely underpowered. TRIAL REGISTRATION: Clinicaltrials.gov NCT01654289",2018 Jun 22,"['Barrett, Bruce', 'Hayney, Mary S.', 'Muller, Daniel', 'Rakel, David', 'Brown, Roger', 'Zgierska, Aleksandra E.', 'Barlow, Shari', 'Hayer, Supriya', 'Barnet, Jodi H.', 'Torres, Elisa R.', 'Coe, Christopher L.']",PLoS One,,,False
1804d84a48b0228ffdc40a1af0eb63d469630852,PMC,Meditation or exercise for preventing acute respiratory infection (MEPARI-2): A randomized controlled trial,http://dx.doi.org/10.1371/journal.pone.0197778,PMC6014660,29933369,CC BY,"BACKGROUND: Practice of meditation or exercise may enhance health to protect against acute infectious illness. OBJECTIVE: To assess preventive effects of meditation and exercise on acute respiratory infection (ARI) illness. DESIGN: Randomized controlled prevention trial with three parallel groups. SETTING: Madison, Wisconsin, USA. PARTICIPANTS: Community-recruited adults who did not regularly exercise or meditate. METHODS: 1) 8-week behavioral training in mindfulness-based stress reduction (MBSR); 2) matched 8-week training in moderate intensity sustained exercise (EX); or 3) observational waitlist control. Training classes occurred in September and October, with weekly ARI surveillance through May. Incidence, duration, and area-under-curve ARI global severity were measured using daily reports on the WURSS-24 during ARI illness. Viruses were identified multiplex PCR. Absenteeism, health care utilization, and psychosocial health self-report assessments were also employed. RESULTS: Of 413 participants randomized, 390 completed the trial. In the MBSR group, 74 experienced 112 ARI episodes with 1045 days of ARI illness. Among exercisers, 84 had 120 episodes totaling 1010 illness days. Eighty-two of the controls had 134 episodes with 1210 days of ARI illness. Mean global severity was 315 for MBSR (95% confidence interval 244, 386), 256 (193, 318) for EX, and 336 (268, 403) for controls. A prespecified multivariate zero-inflated regression model suggested reduced incidence for MBSR (p = 0.036) and lower global severity for EX (p = 0.042), compared to control, not quite attaining the p<0.025 prespecified cut-off for null hypothesis rejection. There were 73 ARI-related missed-work days and 22 ARI-related health care visits in the MBSR group, 82 days and 21 visits for exercisers, and 105 days and 24 visits among controls. Viruses were identified in 63 ARI episodes in the MBSR group, compared to 64 for EX and 72 for control. Statistically significant (p<0.05) improvements in general mental health, self-efficacy, mindful attention, sleep quality, perceived stress, and depressive symptoms were observed in the MBSR and/or EX groups, compared to control. CONCLUSIONS: Training in mindfulness meditation or exercise may help protect against ARI illness. LIMITATIONS: This trial was likely underpowered. TRIAL REGISTRATION: Clinicaltrials.gov NCT01654289",2018 Jun 22,"['Barrett, Bruce', 'Hayney, Mary S.', 'Muller, Daniel', 'Rakel, David', 'Brown, Roger', 'Zgierska, Aleksandra E.', 'Barlow, Shari', 'Hayer, Supriya', 'Barnet, Jodi H.', 'Torres, Elisa R.', 'Coe, Christopher L.']",PLoS One,,,True
3e276874c125f0c8c8490eb41e9ae26cf767447c,PMC,Meditation or exercise for preventing acute respiratory infection (MEPARI-2): A randomized controlled trial,http://dx.doi.org/10.1371/journal.pone.0197778,PMC6014660,29933369,CC BY,"BACKGROUND: Practice of meditation or exercise may enhance health to protect against acute infectious illness. OBJECTIVE: To assess preventive effects of meditation and exercise on acute respiratory infection (ARI) illness. DESIGN: Randomized controlled prevention trial with three parallel groups. SETTING: Madison, Wisconsin, USA. PARTICIPANTS: Community-recruited adults who did not regularly exercise or meditate. METHODS: 1) 8-week behavioral training in mindfulness-based stress reduction (MBSR); 2) matched 8-week training in moderate intensity sustained exercise (EX); or 3) observational waitlist control. Training classes occurred in September and October, with weekly ARI surveillance through May. Incidence, duration, and area-under-curve ARI global severity were measured using daily reports on the WURSS-24 during ARI illness. Viruses were identified multiplex PCR. Absenteeism, health care utilization, and psychosocial health self-report assessments were also employed. RESULTS: Of 413 participants randomized, 390 completed the trial. In the MBSR group, 74 experienced 112 ARI episodes with 1045 days of ARI illness. Among exercisers, 84 had 120 episodes totaling 1010 illness days. Eighty-two of the controls had 134 episodes with 1210 days of ARI illness. Mean global severity was 315 for MBSR (95% confidence interval 244, 386), 256 (193, 318) for EX, and 336 (268, 403) for controls. A prespecified multivariate zero-inflated regression model suggested reduced incidence for MBSR (p = 0.036) and lower global severity for EX (p = 0.042), compared to control, not quite attaining the p<0.025 prespecified cut-off for null hypothesis rejection. There were 73 ARI-related missed-work days and 22 ARI-related health care visits in the MBSR group, 82 days and 21 visits for exercisers, and 105 days and 24 visits among controls. Viruses were identified in 63 ARI episodes in the MBSR group, compared to 64 for EX and 72 for control. Statistically significant (p<0.05) improvements in general mental health, self-efficacy, mindful attention, sleep quality, perceived stress, and depressive symptoms were observed in the MBSR and/or EX groups, compared to control. CONCLUSIONS: Training in mindfulness meditation or exercise may help protect against ARI illness. LIMITATIONS: This trial was likely underpowered. TRIAL REGISTRATION: Clinicaltrials.gov NCT01654289",2018 Jun 22,"['Barrett, Bruce', 'Hayney, Mary S.', 'Muller, Daniel', 'Rakel, David', 'Brown, Roger', 'Zgierska, Aleksandra E.', 'Barlow, Shari', 'Hayer, Supriya', 'Barnet, Jodi H.', 'Torres, Elisa R.', 'Coe, Christopher L.']",PLoS One,,,True
b1bc4e62b880ab407cb7af2514847a38f76df2c7,PMC,A host-protein signature is superior to other biomarkers for differentiating between bacterial and viral disease in patients with respiratory infection and fever without source: a prospective observational study,http://dx.doi.org/10.1007/s10096-018-3261-3,PMC6015097,29700762,CC BY,"Bacterial and viral infections often present with similar symptoms. Etiologic misdiagnosis can alter the trajectory of patient care, including antibiotic overuse. A host-protein signature comprising tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) was validated recently for differentiating bacterial from viral disease. However, a focused head-to-head comparison of its diagnostic performance against other biomarker candidates for this indication was lacking in patients with respiratory infection and fever without source. We compared the signature to other biomarkers and prediction rules using specimens collected prospectively at two secondary medical centers from children and adults. Inclusion criteria included fever > 37.5 °C, symptom duration ≤ 12 days, and presentation with respiratory infection or fever without source. Comparator method was based on expert panel adjudication. Signature and biomarker cutoffs and prediction rules were predefined. Of 493 potentially eligible patients, 314 were assigned unanimous expert panel diagnosis and also had sufficient specimen volume. The resulting cohort comprised 175 (56%) viral and 139 (44%) bacterial infections. Signature sensitivity 93.5% (95% CI 89.1–97.9%), specificity 94.3% (95% CI 90.7–98.0%), or both were significantly higher (all p values < 0.01) than for CRP, procalcitonin, interleukin-6, human neutrophil lipocalin, white blood cell count, absolute neutrophil count, and prediction rules. Signature identified as viral 50/57 viral patients prescribed antibiotics, suggesting potential to reduce antibiotic overuse by 88%. The host-protein signature demonstrated superior diagnostic performance in differentiating viral from bacterial respiratory infections and fever without source. Future utility studies are warranted to validate potential to reduce antibiotic overuse. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-018-3261-3) contains supplementary material, which is available to authorized users.",2018 Apr 26,"['Ashkenazi-Hoffnung, Liat', 'Oved, Kfir', 'Navon, Roy', 'Friedman, Tom', 'Boico, Olga', 'Paz, Meital', 'Kronenfeld, Gali', 'Etshtein, Liat', 'Cohen, Asi', 'Gottlieb, Tanya M.', 'Eden, Eran', 'Chistyakov, Irina', 'Srugo, Isaac', 'Klein, Adi', 'Ashkenazi, Shai', 'Scheuerman, Oded']",Eur J Clin Microbiol Infect Dis,,,True
3a60c19b5cc401e24f815f8924010e77bed7579d,PMC,Cytokine production pattern of T lymphocytes in neonatal arterial ischemic stroke during the first month of life—a case study,http://dx.doi.org/10.1186/s12974-018-1229-y,PMC6015463,29933753,CC BY,"BACKGROUND: The perinatal period carries the highest risk for stroke in childhood; however, the pathophysiology is poorly understood and preventive, prognostic, and therapeutic strategies are not available. A new pathophysiological model describes the development of neonatal arterial ischemic stroke (NAIS) as the combined result of prenatal inflammation and hypoxic–ischemic insult. Neuroinflammation and a systemic inflammatory response are also important features of NAIS. Identifying key players of the inflammatory system is in the limelight of current research. CASE PRESENTATION: We present four NAIS cases, in whom detailed analysis of intracellular and plasma cytokine levels are available from the first month of life. All neonates were admitted with the initial diagnosis of hypoxic ischemic encephalopathy (HIE); however, early MRI examination revealed NAIS. Blood samples were collected between 3 and 6 h of life, at 24 h, 72 h, 1 week, and 1 month of life. Peripheral blood mononuclear cells were assessed with flow cytometry and plasma cytokine levels were measured. Pooled data from the cohort of four NAIS patients were compared to infants with HIE. At 6 and 72 h of age, the prevalence of IL10+ CD8+ lymphocytes remained lower in NAIS. At 6 h, CD8+ lymphocytes in NAIS produced more IL-17. At 72 h, CD8+ cells produced more IL-6 in severe HIE than in NAIS, but IL-6 production remained elevated in CD8 cells at 1 month in NAIS, while it decreased in HIE. At 1 week, the prevalence of TGF-β + lymphocytes prone to enter the CNS was elevated in NAIS. On the other hand, by 1 month of age, the prevalence of TGF-β + CD4+ lymphocytes decreased in NAIS compared to HIE. At 72 h, we found elevated plasma levels of IL-5, MCP-1, and IL-17 in NAIS. By 1 month, plasma levels of IL-4, IL-12, and IL-17 decreased in NAIS but remained elevated in HIE. CONCLUSIONS: Differences in the cytokine network are present between NAIS and HIE. CD8 lymphocytes appear to shift towards the pro-inflammatory direction in NAIS. The inflammatory response appears to be more pronounced at 72 h in NAIS but decreases faster, reaching lower plasma levels of inflammatory markers at 1 month.",2018 Jun 22,"['Bajnok, Anna', 'Berta, László', 'Orbán, Csaba', 'Tulassay, Tivadar', 'Toldi, Gergely']",J Neuroinflammation,,,True
d921cd2d71ffa5577a0d2c534da20f6780b3a564,PMC,The PGRS Domain of Mycobacterium tuberculosis PE_PGRS Protein Rv0297 Is Involved in Endoplasmic Reticulum Stress-Mediated Apoptosis through Toll-Like Receptor 4,http://dx.doi.org/10.1128/mBio.01017-18,PMC6016250,29921671,CC BY,"The genome of Mycobacterium tuberculosis, the causal organism of tuberculosis (TB), encodes a unique protein family known as the PE/PPE/PGRS family, present exclusively in the genus Mycobacterium and nowhere else in the living kingdom, with largely unexplored functions. We describe the functional significance of the PGRS domain of Rv0297, a member of this family. In silico analyses revealed the presence of intrinsically disordered stretches and putative endoplasmic reticulum (ER) localization signals in the PGRS domain of Rv0297 (Rv0297PGRS). The PGRS domain aids in ER localization, which was shown by infecting macrophage cells with M. tuberculosis and by overexpressing the protein by transfection in macrophage cells followed by activation of the unfolded protein response, as evident from increased expression of GRP78/GRP94 and CHOP/ATF4, leading to disruption of intracellular Ca(2+) homeostasis and increased nitric oxide (NO) and reactive oxygen species (ROS) production. The consequent activation of the effector caspase-8 resulted in apoptosis of macrophages, which was Toll-like receptor 4 (TLR4) dependent. Administration of recombinant Rv0297PGRS (rRv0297PGRS) also exhibited similar effects. These results implicate a hitherto-unknown role of the PGRS domain of the PE_PGRS protein family in ER stress-mediated cell death through TLR4. Since this protein is already known to be present at later stages of infection in human granulomas it points to the possibility of it being employed by M. tuberculosis for its dissemination via an apoptotic mechanism.",2018 Jun 19,"['Grover, Sonam', 'Sharma, Tarina', 'Singh, Yadvir', 'Kohli, Sakshi', 'P., Manjunath', 'Singh, Aditi', 'Semmler, Torsten', 'Wieler, Lothar H.', 'Tedin, Karsten', 'Ehtesham, Nasreen Z.', 'Hasnain, Seyed E.']",mBio,,,True
826cfd170048c1d41191762143991575452b0746,PMC,"Health-related quality of life in intensive care survivors: Associations with social support, comorbidity, and pain interference",http://dx.doi.org/10.1371/journal.pone.0199656,PMC6016908,29940026,CC BY,"BACKGROUND: Experiences during a stay in the intensive care unit (ICU), including pain, delirium, physical deterioration, and the critical illness itself, may all influence survivors’ health-related quality of life (HRQOL). However, few studies have examined the influence of social support, comorbidity, and pain interference on ICU survivors’ HRQOL. OBJECTIVES: To investigate possible associations between social support, number of comorbidities, and pain interference on HRQOL in ICU survivors. METHODS: ICU survivors responded to a survey 3 months (n = 118) and 1 year (n = 89) after ICU discharge. HRQOL was measured using the Short Form Health Survey-12 (v1), social support using the revised Social Provision Scale, pain interference using the Brief Pain Inventory–Short Form, and comorbidities using the Self-Administered Comorbidity Questionnaire. RESULTS: Physical and mental HRQOL were reduced at both 3 months and 1 year in ICU survivors compared with the general population. This reduction was more pronounced at 3 months for physical HRQOL, while a small reduction in mental HRQOL was not clinically relevant. Social support was statistical significantly positively associated with mental HRQOL at 3 months, while number of comorbidities was statistical significantly associated with a reduction in physical HRQOL at 3 months and 1 year and mental HRQOL at 1 year. Lastly pain interference was significantly associated with a reduction in physical HRQOL at 3 months and 1 year. CONCLUSIONS: ICU survivors primarily report reduced physical HRQOL. Social support was positively associated with mental HRQOL, while number of comorbidities, and pain interference were all significantly associated with a reduction in HRQOL. Pain interference was associated with the largest reduction in HRQOL.",2018 Jun 25,"['Langerud, Anne Kathrine', 'Rustøen, Tone', 'Småstuen, Milada Cvancarova', 'Kongsgaard, Ulf', 'Stubhaug, Audun']",PLoS One,,,True
53a126d28e3dee03d1bcda8154f4070e26212770,PMC,Chemical Modification of Chitosan for Efficient Vaccine Delivery,http://dx.doi.org/10.3390/molecules23020229,PMC6017229,29370100,CC BY,"Chitosan, which exhibits good biocompatibility, safety, microbial degradation and other excellent performances, has found application in all walks of life. In the field of medicine, usage of chitosan for the delivery of vaccine is favored by a wide range of researchers. However, due to its own natural limitations, its application has been constrained to the beginning of study. In order to improve the applicability for vaccine delivery, researchers have carried out various chemical modifications of chitosan. This review summarizes a variety of modification methods and applications of chitosan and its derivatives in the field of vaccine delivery.",2018 Jan 25,"['Xing, Lei', 'Fan, Ya-Tong', 'Zhou, Tian-Jiao', 'Gong, Jia-Hui', 'Cui, Lian-Hua', 'Cho, Ki-Hyun', 'Choi, Yun-Jaie', 'Jiang, Hu-Lin', 'Cho, Chong-Su']",Molecules,,,True
d9a66cbdd96e0bce18bc370c96ef5e71c5a7a27d,PMC,Efficient Separation of Four Antibacterial Diterpenes from the Roots of Salvia Prattii Using Non-Aqueous Hydrophilic Solid-Phase Extraction Followed by Preparative High-Performance Liquid Chromatography,http://dx.doi.org/10.3390/molecules23030623,PMC6017395,29522496,CC BY,"An efficient preparative procedure for the separation of four antibacterial diterpenes from a Salvia prattii crude diterpenes-rich sample was developed. Firstly, the XION hydrophilic stationary phase was chosen to separate the antibacterial crude diterpenes-rich sample (18.0 g) into three fractions with a recovery of 46.1%. Then, the antibacterial fractions I (200 mg), II (200 mg), and III (150 g) were separated by the Megress C18 preparative column, and compounds tanshinone IIA (80.0 mg), salvinolone (62.0 mg), cryptotanshinone (70.0 mg), and ferruginol (68.0 mg) were produced with purities greater than 98%. The procedure achieved large-scale preparation of the four diterpenes with high purity, and it could act as a reference for the efficient preparation of active diterpenes from other plant extracts.",2018 Mar 9,"['Dang, Jun', 'Cui, Yulei', 'Pei, Jinjin', 'Yue, Huilan', 'Liu, Zenggen', 'Wang, Weidong', 'Jiao, Lijin', 'Mei, Lijuan', 'Wang, Qilan', 'Tao, Yanduo', 'Shao, Yun']",Molecules,,,True
f595066c0454a407001920c8baf1edb260e9bb9d,PMC,RPiRLS: Quantitative Predictions of RNA Interacting with Any Protein of Known Sequence,http://dx.doi.org/10.3390/molecules23030540,PMC6017498,29495575,CC BY,"RNA-protein interactions (RPIs) have critical roles in numerous fundamental biological processes, such as post-transcriptional gene regulation, viral assembly, cellular defence and protein synthesis. As the number of available RNA-protein binding experimental data has increased rapidly due to high-throughput sequencing methods, it is now possible to measure and understand RNA-protein interactions by computational methods. In this study, we integrate a sequence-based derived kernel with regularized least squares to perform prediction. The derived kernel exploits the contextual information around an amino acid or a nucleic acid as well as the repetitive conserved motif information. We propose a novel machine learning method, called RPiRLS to predict the interaction between any RNA and protein of known sequences. For the RPiRLS classifier, each protein sequence comprises up to 20 diverse amino acids but for the RPiRLS-7G classifier, each protein sequence is represented by using 7-letter reduced alphabets based on their physiochemical properties. We evaluated both methods on a number of benchmark data sets and compared their performances with two newly developed and state-of-the-art methods, RPI-Pred and IPMiner. On the non-redundant benchmark test sets extracted from the PRIDB, the RPiRLS method outperformed RPI-Pred and IPMiner in terms of accuracy, specificity and sensitivity. Further, RPiRLS achieved an accuracy of 92% on the prediction of lncRNA-protein interactions. The proposed method can also be extended to construct RNA-protein interaction networks. The RPiRLS web server is freely available at http://bmc.med.stu.edu.cn/RPiRLS.",2018 Feb 28,"['Shen, Wen-Jun', 'Cui, Wenjuan', 'Chen, Danze', 'Zhang, Jieming', 'Xu, Jianzhen']",Molecules,,,True
eb7682d19e11ed030c9541c61514075c2080535a,PMC,Evaluation of Targeted Next-Generation Sequencing for Detection of Bovine Pathogens in Clinical Samples,http://dx.doi.org/10.1128/JCM.00399-18,PMC6018347,29695524,CC BY,"The laboratory diagnosis of infectious diseases, especially those caused by mixed infections, is challenging. Routinely, it requires submission of multiple samples to separate laboratories. Advances in next-generation sequencing (NGS) have provided the opportunity for development of a comprehensive method to identify infectious agents. This study describes the use of target-specific primers for PCR-mediated amplification with the NGS technology in which pathogen genomic regions of interest are enriched and selectively sequenced from clinical samples. In the study, 198 primers were designed to target 43 common bovine and small-ruminant bacterial, fungal, viral, and parasitic pathogens, and a bioinformatics tool was specifically constructed for the detection of targeted pathogens. The primers were confirmed to detect the intended pathogens by testing reference strains and isolates. The method was then validated using 60 clinical samples (including tissues, feces, and milk) that were also tested with other routine diagnostic techniques. The detection limits of the targeted NGS method were evaluated using 10 representative pathogens that were also tested by quantitative PCR (qPCR), and the NGS method was able to detect the organisms from samples with qPCR threshold cycle (C(T)) values in the 30s. The method was successful for the detection of multiple pathogens in the clinical samples, including some additional pathogens missed by the routine techniques because the specific tests needed for the particular organisms were not performed. The results demonstrate the feasibility of the approach and indicate that it is possible to incorporate NGS as a diagnostic tool in a cost-effective manner into a veterinary diagnostic laboratory.",2018 Jun 25,"['Anis, Eman', 'Hawkins, Ian K.', 'Ilha, Marcia R. S.', 'Woldemeskel, Moges W.', 'Saliki, Jeremiah T.', 'Wilkes, Rebecca P.']",J Clin Microbiol,,,True
35f029b40611c03be25c0c2e0e8a9731e7ed4643,PMC,Standardized Preparation for Fecal Microbiota Transplantation in Pigs,http://dx.doi.org/10.3389/fmicb.2018.01328,PMC6018536,29971061,CC BY,"The intestine of pigs harbors a mass of microorganisms which are essential for intestinal homeostasis and host health. Intestinal microbial disorders induce enteric inflammation and metabolic dysfunction, thereby causing adverse effects on the growth and health of pigs. In the human medicine, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, has shown efficacy in intestinal microbiota restoration. In addition, it has been used widely in therapy for human gastrointestinal diseases, including Clostridium difficile infection, inflammatory bowel diseases, and irritable bowel syndrome. Given that pigs share many similarities with humans, in terms of anatomy, nutritional physiology, and intestinal microbial compositions, FMT may also be used to restore the normal intestinal microbiota of pigs. However, feasible procedures for performing FMT in pigs remains unclear. Here, we summarize a standardized preparation for FMT in pigs by combining the standard methodology for human FMT with pig production. The key issues include the donor selection, fecal material preparation, fecal material transfer, stool bank establishment, and the safety for porcine FMT. Optimal donors should be selected to ensure the efficacy of porcine FMT and reduce the risks of transmitting infectious diseases to recipients during FMT. Preparing for fresh fecal material is highly recommended. Alternatively, frozen fecal suspension can also be prepared as an optimal choice because it is convenient and has similar efficacy. Oral administration of fecal suspension could be an optimal method for porcine fecal material transfer. Furthermore, the dilution ratio of fecal materials and the frequency of fecal material transfer could be adjusted according to practical situations in the pig industry. To meet the potential large-scale requirement in the pig industry, it is important to establish a stool bank to make porcine FMT readily available. Future studies should also focus on providing more robust safety data on FMT to improve the safety and tolerability of the recipient pigs. This standardized preparation for porcine FMT can facilitate the development of microbial targeted therapies and improve the intestinal health of pigs.",2018 Jun 19,"['Hu, Jun', 'Chen, Lingli', 'Tang, Yimei', 'Xie, Chunlin', 'Xu, Baoyang', 'Shi, Min', 'Zheng, Wenyong', 'Zhou, Shuyi', 'Wang, Xinkai', 'Liu, Liu', 'Yan, Yiqin', 'Yang, Tao', 'Niu, Yaorong', 'Hou, Qiliang', 'Xu, Xiaofan', 'Yan, Xianghua']",Front Microbiol,,,True
b7737ffbdfa3d743dc16b4f99b0a85646529af3d,PMC,Estimating spatiotemporally varying malaria reproduction numbers in a near elimination setting,http://dx.doi.org/10.1038/s41467-018-04577-y,PMC6018772,29946060,CC BY,"In 2016 the World Health Organization identified 21 countries that could eliminate malaria by 2020. Monitoring progress towards this goal requires tracking ongoing transmission. Here we develop methods that estimate individual reproduction numbers and their variation through time and space. Individual reproduction numbers, R(c), describe the state of transmission at a point in time and differ from mean reproduction numbers, which are averages of the number of people infected by a typical case. We assess elimination progress in El Salvador using data for confirmed cases of malaria from 2010 to 2016. Our results demonstrate that whilst the average number of secondary malaria cases was below one (0.61, 95% CI 0.55–0.65), individual reproduction numbers often exceeded one. We estimate a decline in R(c) between 2010 and 2016. However we also show that if importation is maintained at the same rate, the country may not achieve malaria elimination by 2020.",2018 Jun 26,"['Routledge, Isobel', 'Chevéz, José Eduardo Romero', 'Cucunubá, Zulma M.', 'Rodriguez, Manuel Gomez', 'Guinovart, Caterina', 'Gustafson, Kyle B.', 'Schneider, Kammerle', 'Walker, Patrick G.T.', 'Ghani, Azra C.', 'Bhatt, Samir']",Nat Commun,,,True
6a7cec5919100b5ee95c8c84b99455a7611bc79c,PMC,Estimating spatiotemporally varying malaria reproduction numbers in a near elimination setting,http://dx.doi.org/10.1038/s41467-018-04577-y,PMC6018772,29946060,CC BY,"In 2016 the World Health Organization identified 21 countries that could eliminate malaria by 2020. Monitoring progress towards this goal requires tracking ongoing transmission. Here we develop methods that estimate individual reproduction numbers and their variation through time and space. Individual reproduction numbers, R(c), describe the state of transmission at a point in time and differ from mean reproduction numbers, which are averages of the number of people infected by a typical case. We assess elimination progress in El Salvador using data for confirmed cases of malaria from 2010 to 2016. Our results demonstrate that whilst the average number of secondary malaria cases was below one (0.61, 95% CI 0.55–0.65), individual reproduction numbers often exceeded one. We estimate a decline in R(c) between 2010 and 2016. However we also show that if importation is maintained at the same rate, the country may not achieve malaria elimination by 2020.",2018 Jun 26,"['Routledge, Isobel', 'Chevéz, José Eduardo Romero', 'Cucunubá, Zulma M.', 'Rodriguez, Manuel Gomez', 'Guinovart, Caterina', 'Gustafson, Kyle B.', 'Schneider, Kammerle', 'Walker, Patrick G.T.', 'Ghani, Azra C.', 'Bhatt, Samir']",Nat Commun,,,True
a5b3f4df4b5b773e35f56703b5a653559e82b139,PMC,Estimating spatiotemporally varying malaria reproduction numbers in a near elimination setting,http://dx.doi.org/10.1038/s41467-018-04577-y,PMC6018772,29946060,CC BY,"In 2016 the World Health Organization identified 21 countries that could eliminate malaria by 2020. Monitoring progress towards this goal requires tracking ongoing transmission. Here we develop methods that estimate individual reproduction numbers and their variation through time and space. Individual reproduction numbers, R(c), describe the state of transmission at a point in time and differ from mean reproduction numbers, which are averages of the number of people infected by a typical case. We assess elimination progress in El Salvador using data for confirmed cases of malaria from 2010 to 2016. Our results demonstrate that whilst the average number of secondary malaria cases was below one (0.61, 95% CI 0.55–0.65), individual reproduction numbers often exceeded one. We estimate a decline in R(c) between 2010 and 2016. However we also show that if importation is maintained at the same rate, the country may not achieve malaria elimination by 2020.",2018 Jun 26,"['Routledge, Isobel', 'Chevéz, José Eduardo Romero', 'Cucunubá, Zulma M.', 'Rodriguez, Manuel Gomez', 'Guinovart, Caterina', 'Gustafson, Kyle B.', 'Schneider, Kammerle', 'Walker, Patrick G.T.', 'Ghani, Azra C.', 'Bhatt, Samir']",Nat Commun,,,True
f6f9df0c4bf4a1d1b2a045660350523c0300f3e3,PMC,Ciliated conical epithelial cell protrusions point towards a diagnosis of primary ciliary dyskinesia,http://dx.doi.org/10.1186/s12931-018-0782-3,PMC6019300,29940967,CC BY,"BACKGROUND: Primary ciliary dyskinesia can result from a number of different ciliary defects that adversely affect ciliary function resulting markedly reduced or absent mucociliary clearance. Improvement in diagnostic testing is an area of current research. During diagnostic evaluation of PCD we observed ciliated conical protrusions from part of the apical surface of ciliated cells in those diagnosed with PCD. The aim of this study was to investigate if this abnormality was specific to PCD. METHODS: Epithelial edges from 67 consecutively diagnosed PCD patients, 67 patients consecutively referred for PCD diagnostic testing in whom PCD was excluded, 22 with asthma and 18 with Cystic Fibrosis (CF) were studied retrospectively in a blinded manner using light microscopy. RESULTS: Forty six out of 67 patients with PCD had ciliated conical epithelial protrusions, whereas none were seen in patients where PCD was excluded, or in patients with asthma or CF. The sensitivity, specificity, positive predictive value and negative predictive value for the presence of the ciliated conical protrusions to predict a diagnosis of PCD were 76.5, 100, 100 and 77% respectively. CONCLUSIONS: Characteristic ciliated conical protrusions from ciliated epithelial cells maybe a useful pointer to the diagnosis of PCD. However, their absence does not exclude the diagnosis of PCD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-018-0782-3) contains supplementary material, which is available to authorized users.",2018 Jun 25,"['O’Callaghan, Chris', 'Rutman, Andrew', 'Williams, Gwyneth', 'Kulkarni, Neeta', 'Hayes, Joseph', 'Hirst, Robert A.']",Respir Res,,,True
923eca0b4175d09814a117b685e434c2f93bc25c,PMC,Bovine respiratory syncytial virus seroprevalence and risk factors in non-vaccinated dairy cattle herds in Brazil,http://dx.doi.org/10.1186/s12917-018-1535-8,PMC6020315,29945679,CC BY,"BACKGROUND: The cattle industry is one of the most important Brazilian agribusiness sectors and is a strong contributor to the national economy. Annually about 44.6 million calves are bred, which makes the optimal management of these animals extremely important. Several diseases can affect the initial stages of the bovine production chain, being the bovine respiratory syncytial virus (BRSV) one of the most relevant pathogens. This study aimed to characterize the epidemiology of BRSV infection in dairy cattle herds of São Paulo State, Brazil, using serological and risk factors analyses. For that, 1243 blood samples were collected of animals from 26 farms and a questionnaire about possible risk factors for BRSV prevalence was performed. The obtained blood sera were analyzed using virus neutralization test (VNT). RESULTS: VNT results showed high BRSV prevalence in dairy cattle herds, reaching 79.5% of seropositivity. The BRSV seroprevalence among studied farms ranged from 40 to 100%. The analysis of risk factors indicated that the age group and the occurrence of coinfection with bovine herpesvirus 1 (BoHV-1) and bovine viral diarrhea virus 1 (BVDV-1) should be associated with a higher prevalence of BRSV, while natural suckling was considered a protective factor. CONCLUSIONS: The study showed that adult animals over 1 year old are an important risk factor for the high seroprevalence of BRSV in herds. The high BRSV prevalence associated with BoHV-1 and BVDV-1 suggests that biosecurity measures should be applied in order to reduce viral dissemination. Additionally, the natural suckling may be an important management to protect calves from high BRSV seroprevalence.",2018 Jun 27,"['Hoppe, Ingrid Bortolin Affonso Lux', 'Medeiros, Andréa Souza Ramos de', 'Arns, Clarice Weis', 'Samara, Samir Issa']",BMC Vet Res,,,True
1dafe663fcb23f0b8568d997f2e571aaa881bdf2,PMC,Dissecting ribosomal particles throughout the kingdoms of life using advanced hybrid mass spectrometry methods,http://dx.doi.org/10.1038/s41467-018-04853-x,PMC6021402,29950687,CC BY,"Biomolecular mass spectrometry has matured strongly over the past decades and has now reached a stage where it can provide deep insights into the structure and composition of large cellular assemblies. Here, we describe a three-tiered hybrid mass spectrometry approach that enables the dissection of macromolecular complexes in order to complement structural studies. To demonstrate the capabilities of the approach, we investigate ribosomes, large ribonucleoprotein particles consisting of a multitude of protein and RNA subunits. We identify sites of sequence processing, protein post-translational modifications, and the assembly and stoichiometry of individual ribosomal proteins in four distinct ribosomal particles of bacterial, plant and human origin. Amongst others, we report extensive cysteine methylation in the zinc finger domain of the human S27 protein, the heptameric stoichiometry of the chloroplastic stalk complex, the heterogeneous composition of human 40S ribosomal subunits and their association to the CrPV, and HCV internal ribosome entry site RNAs.",2018 Jun 27,"['van de Waterbeemd, Michiel', 'Tamara, Sem', 'Fort, Kyle L.', 'Damoc, Eugen', 'Franc, Vojtech', 'Bieri, Philipp', 'Itten, Martin', 'Makarov, Alexander', 'Ban, Nenad', 'Heck, Albert J. R.']",Nat Commun,,,False
ed949018063b4372e455612a570fb0a5c97c97a8,PMC,Dissecting ribosomal particles throughout the kingdoms of life using advanced hybrid mass spectrometry methods,http://dx.doi.org/10.1038/s41467-018-04853-x,PMC6021402,29950687,CC BY,"Biomolecular mass spectrometry has matured strongly over the past decades and has now reached a stage where it can provide deep insights into the structure and composition of large cellular assemblies. Here, we describe a three-tiered hybrid mass spectrometry approach that enables the dissection of macromolecular complexes in order to complement structural studies. To demonstrate the capabilities of the approach, we investigate ribosomes, large ribonucleoprotein particles consisting of a multitude of protein and RNA subunits. We identify sites of sequence processing, protein post-translational modifications, and the assembly and stoichiometry of individual ribosomal proteins in four distinct ribosomal particles of bacterial, plant and human origin. Amongst others, we report extensive cysteine methylation in the zinc finger domain of the human S27 protein, the heptameric stoichiometry of the chloroplastic stalk complex, the heterogeneous composition of human 40S ribosomal subunits and their association to the CrPV, and HCV internal ribosome entry site RNAs.",2018 Jun 27,"['van de Waterbeemd, Michiel', 'Tamara, Sem', 'Fort, Kyle L.', 'Damoc, Eugen', 'Franc, Vojtech', 'Bieri, Philipp', 'Itten, Martin', 'Makarov, Alexander', 'Ban, Nenad', 'Heck, Albert J. R.']",Nat Commun,,,False
0d8967499181dce60d2f6b813955539e9b3007e3,PMC,Dissecting ribosomal particles throughout the kingdoms of life using advanced hybrid mass spectrometry methods,http://dx.doi.org/10.1038/s41467-018-04853-x,PMC6021402,29950687,CC BY,"Biomolecular mass spectrometry has matured strongly over the past decades and has now reached a stage where it can provide deep insights into the structure and composition of large cellular assemblies. Here, we describe a three-tiered hybrid mass spectrometry approach that enables the dissection of macromolecular complexes in order to complement structural studies. To demonstrate the capabilities of the approach, we investigate ribosomes, large ribonucleoprotein particles consisting of a multitude of protein and RNA subunits. We identify sites of sequence processing, protein post-translational modifications, and the assembly and stoichiometry of individual ribosomal proteins in four distinct ribosomal particles of bacterial, plant and human origin. Amongst others, we report extensive cysteine methylation in the zinc finger domain of the human S27 protein, the heptameric stoichiometry of the chloroplastic stalk complex, the heterogeneous composition of human 40S ribosomal subunits and their association to the CrPV, and HCV internal ribosome entry site RNAs.",2018 Jun 27,"['van de Waterbeemd, Michiel', 'Tamara, Sem', 'Fort, Kyle L.', 'Damoc, Eugen', 'Franc, Vojtech', 'Bieri, Philipp', 'Itten, Martin', 'Makarov, Alexander', 'Ban, Nenad', 'Heck, Albert J. R.']",Nat Commun,,,False
5278efe68b31540a1a68ecf36528c7dd4a5fa14d,PMC,Dissecting ribosomal particles throughout the kingdoms of life using advanced hybrid mass spectrometry methods,http://dx.doi.org/10.1038/s41467-018-04853-x,PMC6021402,29950687,CC BY,"Biomolecular mass spectrometry has matured strongly over the past decades and has now reached a stage where it can provide deep insights into the structure and composition of large cellular assemblies. Here, we describe a three-tiered hybrid mass spectrometry approach that enables the dissection of macromolecular complexes in order to complement structural studies. To demonstrate the capabilities of the approach, we investigate ribosomes, large ribonucleoprotein particles consisting of a multitude of protein and RNA subunits. We identify sites of sequence processing, protein post-translational modifications, and the assembly and stoichiometry of individual ribosomal proteins in four distinct ribosomal particles of bacterial, plant and human origin. Amongst others, we report extensive cysteine methylation in the zinc finger domain of the human S27 protein, the heptameric stoichiometry of the chloroplastic stalk complex, the heterogeneous composition of human 40S ribosomal subunits and their association to the CrPV, and HCV internal ribosome entry site RNAs.",2018 Jun 27,"['van de Waterbeemd, Michiel', 'Tamara, Sem', 'Fort, Kyle L.', 'Damoc, Eugen', 'Franc, Vojtech', 'Bieri, Philipp', 'Itten, Martin', 'Makarov, Alexander', 'Ban, Nenad', 'Heck, Albert J. R.']",Nat Commun,,,True
d209dfa336d8a793ddb03e18fa7b27a1bf2dfaea,PMC,"Human coronavirus OC43 outbreak in wild chimpanzees, Côte d´Ivoire, 2016",http://dx.doi.org/10.1038/s41426-018-0121-2,PMC6021434,29950583,CC BY,,2018 Jun 27,"['Patrono, Livia V.', 'Samuni, Liran', 'Corman, Victor M.', 'Nourifar, Leila', 'Röthemeier, Caroline', 'Wittig, Roman M.', 'Drosten, Christian', 'Calvignac-Spencer, Sébastien', 'Leendertz, Fabian H.']",Emerg Microbes Infect,,,False
1697b728990d9c326f6c7df56cb0f34f968876ac,PMC,"Human coronavirus OC43 outbreak in wild chimpanzees, Côte d´Ivoire, 2016",http://dx.doi.org/10.1038/s41426-018-0121-2,PMC6021434,29950583,CC BY,,2018 Jun 27,"['Patrono, Livia V.', 'Samuni, Liran', 'Corman, Victor M.', 'Nourifar, Leila', 'Röthemeier, Caroline', 'Wittig, Roman M.', 'Drosten, Christian', 'Calvignac-Spencer, Sébastien', 'Leendertz, Fabian H.']",Emerg Microbes Infect,,,False
2bc264fbfdad15fb4ef382db12714a5ed5ceabe0,PMC,"Human coronavirus OC43 outbreak in wild chimpanzees, Côte d´Ivoire, 2016",http://dx.doi.org/10.1038/s41426-018-0121-2,PMC6021434,29950583,CC BY,,2018 Jun 27,"['Patrono, Livia V.', 'Samuni, Liran', 'Corman, Victor M.', 'Nourifar, Leila', 'Röthemeier, Caroline', 'Wittig, Roman M.', 'Drosten, Christian', 'Calvignac-Spencer, Sébastien', 'Leendertz, Fabian H.']",Emerg Microbes Infect,,,True
7aba26bb74cef3ffdae571ebe3d9d3fae1d1df4f,PMC,Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4,http://dx.doi.org/10.1038/s41598-018-28109-2,PMC6021449,29950581,CC BY,"Middle East respiratory syndrome (MERS) represents an important respiratory disease accompanied by lethal outcome in one-third of human patients. Recent data indicate that dromedaries represent an important source of infection, although information regarding viral cell tropism and pathogenesis is sparse. In the current study, tissues of eight dromedaries receiving inoculation of MERS-Coronavirus (MERS-CoV) after recombinant Modified-Vaccinia-Virus-Ankara (MVA-S)-vaccination (n = 4), MVA-vaccination (mock vaccination, n = 2) and PBS application (mock vaccination, n = 2), respectively, were investigated. Tissues were analyzed by histology, immunohistochemistry, immunofluorescence, and scanning electron microscopy. MERS-CoV infection in mock-vaccinated dromedaries revealed high numbers of MERS-CoV-nucleocapsid positive cells, T cells, and macrophages within nasal turbinates and trachea at day four post infection. Double immunolabeling demonstrated cytokeratin (CK) 18 expressing epithelial cells to be the prevailing target cell of MERS-CoV, while CK5/6 and CK14 expressing cells did not co-localize with virus. In addition, virus was occasionally detected in macrophages. The acute disease was further accompanied by ciliary loss along with a lack of dipeptidyl peptidase 4 (DPP4), known to mediate virus entry. DPP4 was mainly expressed by human lymphocytes and dromedary monocytes, but overall the expression level was lower in dromedaries. The present study underlines significant species-specific manifestations of MERS and highlights ciliary loss as an important finding in dromedaries. The obtained results promote a better understanding of coronavirus infections, which pose major health challenges.",2018 Jun 27,"['Haverkamp, Ann-Kathrin', 'Lehmbecker, Annika', 'Spitzbarth, Ingo', 'Widagdo, Widagdo', 'Haagmans, Bart L.', 'Segalés, Joaquim', 'Vergara-Alert, Julia', 'Bensaid, Albert', 'van den Brand, Judith M. A.', 'Osterhaus, Albert D. M. E.', 'Baumgärtner, Wolfgang']",Sci Rep,,,False
01234cee305e37a78cedea8148bf6177d47fe66b,PMC,Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4,http://dx.doi.org/10.1038/s41598-018-28109-2,PMC6021449,29950581,CC BY,"Middle East respiratory syndrome (MERS) represents an important respiratory disease accompanied by lethal outcome in one-third of human patients. Recent data indicate that dromedaries represent an important source of infection, although information regarding viral cell tropism and pathogenesis is sparse. In the current study, tissues of eight dromedaries receiving inoculation of MERS-Coronavirus (MERS-CoV) after recombinant Modified-Vaccinia-Virus-Ankara (MVA-S)-vaccination (n = 4), MVA-vaccination (mock vaccination, n = 2) and PBS application (mock vaccination, n = 2), respectively, were investigated. Tissues were analyzed by histology, immunohistochemistry, immunofluorescence, and scanning electron microscopy. MERS-CoV infection in mock-vaccinated dromedaries revealed high numbers of MERS-CoV-nucleocapsid positive cells, T cells, and macrophages within nasal turbinates and trachea at day four post infection. Double immunolabeling demonstrated cytokeratin (CK) 18 expressing epithelial cells to be the prevailing target cell of MERS-CoV, while CK5/6 and CK14 expressing cells did not co-localize with virus. In addition, virus was occasionally detected in macrophages. The acute disease was further accompanied by ciliary loss along with a lack of dipeptidyl peptidase 4 (DPP4), known to mediate virus entry. DPP4 was mainly expressed by human lymphocytes and dromedary monocytes, but overall the expression level was lower in dromedaries. The present study underlines significant species-specific manifestations of MERS and highlights ciliary loss as an important finding in dromedaries. The obtained results promote a better understanding of coronavirus infections, which pose major health challenges.",2018 Jun 27,"['Haverkamp, Ann-Kathrin', 'Lehmbecker, Annika', 'Spitzbarth, Ingo', 'Widagdo, Widagdo', 'Haagmans, Bart L.', 'Segalés, Joaquim', 'Vergara-Alert, Julia', 'Bensaid, Albert', 'van den Brand, Judith M. A.', 'Osterhaus, Albert D. M. E.', 'Baumgärtner, Wolfgang']",Sci Rep,,,True
915266f52a5f9c7360670df5de7b51d20e0a8cfa,PMC,The US Military Commitment to Vaccine Development: A Century of Successes and Challenges,http://dx.doi.org/10.3389/fimmu.2018.01397,PMC6021486,29977239,CC BY,"The US military has been a leading proponent of vaccine development since its founding. General George Washington ordered the entire American army to be variolated against smallpox after recognizing the serious threat that it posed to military operations. He did this on the recommendation from Dr. John Morgan, the physician-in-chief of the American army, who wrote a treatise on variolation in 1776. Although cases of smallpox still occurred, they were far fewer than expected, and it is believed that the vaccination program contributed to victory in the War of Independence. Effective military force requires personnel who are healthy and combat ready for worldwide deployment. Given the geography of US military operations, military personnel should also be protected against diseases that are endemic in potential areas of conflict. For this reason, and unknown to many, the US military has strongly supported vaccine research and development. Four categories of communicable infectious diseases threaten military personnel: (1) diseases that spread easily in densely populated areas (respiratory and dysenteric diseases); (2) vector-borne diseases (disease carried by mosquitoes and other insects); (3) sexually transmitted diseases (hepatitis, HIV, and gonorrhea); and (4) diseases associated with biological warfare. For each category, the US military has supported research that has provided the basis for many of the vaccines available today. Although preventive measures and the development of drugs have provided some relief from the burden of malaria, dengue, and HIV, the US military continues to fund research and development of prophylactic vaccines that will contribute to force health protection and global health. In the past few years, newly recognized infections with Zika, severe acute respiratory syndrome, Middle East respiratory syndrome viruses have pushed the US military to fund research and fast track clinical trials to quickly and effectively develop vaccines for emerging diseases. With US military personnel present in every region of the globe, one of the most cost-effective ways to maintain military effectiveness is to develop vaccines against prioritized threats to military members’ health.",2018 Jun 21,"['Ratto-Kim, Silvia', 'Yoon, In-Kyu', 'Paris, Robert M.', 'Excler, Jean-Louis', 'Kim, Jerome H.', 'O’Connell, Robert J.']",Front Immunol,,,True
8ee7ec977aa10ef8bbe5633d5dc6bb9793572508,PMC,Characterization of the Anti-Hepatitis C Virus Activity of New Nonpeptidic Small-Molecule Cyclophilin Inhibitors with the Potential for Broad Anti-Flaviviridae Activity,http://dx.doi.org/10.1128/AAC.00126-18,PMC6021681,29760125,CC BY,"Although members of the Flaviviridae display high incidence, morbidity, and mortality rates, the development of specific antiviral drugs for each virus is unlikely. Cyclophilins, a family of host peptidyl-prolyl cis-trans isomerases (PPIases), play a pivotal role in the life cycles of many viruses and therefore represent an attractive target for broad-spectrum antiviral development. We report here the pangenotypic anti-hepatitis C virus (HCV) activity of a small-molecule cyclophilin inhibitor (SMCypI). Mechanistic and modeling studies revealed that the SMCypI bound to cyclophilin A in competition with cyclosporine (CsA), inhibited its PPIase activity, and disrupted the CypA-nonstructural protein 5A (NS5A) interaction. Resistance selection showed that the lead SMCypI hardly selected amino acid substitutions conferring low-level or no resistance in vitro. Interestingly, the SMCypI selected D320E and Y321H substitutions, located in domain II of the NS5A protein. These substitutions were previously associated with low-level resistance to cyclophilin inhibitors such as alisporivir. Finally, the SMCypI inhibited the replication of other members of the Flaviviridae family with higher 50% effective concentrations (EC(50)s) than for HCV. Thus, because of its chemical plasticity and simplicity of synthesis, our new family of SMCypIs represents a promising new class of drugs with the potential for broad-spectrum anti-Flaviviridae activity as well as an invaluable tool to explore the role of cyclophilins in viral life cycles.",2018 Jun 26,"['Nevers, Quentin', 'Ruiz, Isaac', 'Ahnou, Nazim', 'Donati, Flora', 'Brillet, Rozenn', 'Softic, Laurent', 'Chazal, Maxime', 'Jouvenet, Nolwenn', 'Fourati, Slim', 'Baudesson, Camille', 'Bruscella, Patrice', 'Gelin, Muriel', 'Guichou, Jean-François', 'Pawlotsky, Jean-Michel', 'Ahmed-Belkacem, Abdelhakim']",Antimicrob Agents Chemother,,,True
1c60d93cd686bb14fac65510ad3de47cf8b9332c,PMC,Characterization of the Anti-Hepatitis C Virus Activity of New Nonpeptidic Small-Molecule Cyclophilin Inhibitors with the Potential for Broad Anti-Flaviviridae Activity,http://dx.doi.org/10.1128/AAC.00126-18,PMC6021681,29760125,CC BY,"Although members of the Flaviviridae display high incidence, morbidity, and mortality rates, the development of specific antiviral drugs for each virus is unlikely. Cyclophilins, a family of host peptidyl-prolyl cis-trans isomerases (PPIases), play a pivotal role in the life cycles of many viruses and therefore represent an attractive target for broad-spectrum antiviral development. We report here the pangenotypic anti-hepatitis C virus (HCV) activity of a small-molecule cyclophilin inhibitor (SMCypI). Mechanistic and modeling studies revealed that the SMCypI bound to cyclophilin A in competition with cyclosporine (CsA), inhibited its PPIase activity, and disrupted the CypA-nonstructural protein 5A (NS5A) interaction. Resistance selection showed that the lead SMCypI hardly selected amino acid substitutions conferring low-level or no resistance in vitro. Interestingly, the SMCypI selected D320E and Y321H substitutions, located in domain II of the NS5A protein. These substitutions were previously associated with low-level resistance to cyclophilin inhibitors such as alisporivir. Finally, the SMCypI inhibited the replication of other members of the Flaviviridae family with higher 50% effective concentrations (EC(50)s) than for HCV. Thus, because of its chemical plasticity and simplicity of synthesis, our new family of SMCypIs represents a promising new class of drugs with the potential for broad-spectrum anti-Flaviviridae activity as well as an invaluable tool to explore the role of cyclophilins in viral life cycles.",2018 Jun 26,"['Nevers, Quentin', 'Ruiz, Isaac', 'Ahnou, Nazim', 'Donati, Flora', 'Brillet, Rozenn', 'Softic, Laurent', 'Chazal, Maxime', 'Jouvenet, Nolwenn', 'Fourati, Slim', 'Baudesson, Camille', 'Bruscella, Patrice', 'Gelin, Muriel', 'Guichou, Jean-François', 'Pawlotsky, Jean-Michel', 'Ahmed-Belkacem, Abdelhakim']",Antimicrob Agents Chemother,,,True
539ebc16737a7d43b43c582f3b625050c2bff9a8,PMC,"Forecasting influenza epidemics by integrating internet search queries and traditional surveillance data with the support vector machine regression model in Liaoning, from 2011 to 2015",http://dx.doi.org/10.7717/peerj.5134,PMC6022725,29967755,CC BY,"BACKGROUND: Influenza epidemics pose significant social and economic challenges in China. Internet search query data have been identified as a valuable source for the detection of emerging influenza epidemics. However, the selection of the search queries and the adoption of prediction methods are crucial challenges when it comes to improving predictions. The purpose of this study was to explore the application of the Support Vector Machine (SVM) regression model in merging search engine query data and traditional influenza data. METHODS: The official monthly reported number of influenza cases in Liaoning province in China was acquired from the China National Scientific Data Center for Public Health from January 2011 to December 2015. Based on Baidu Index, a publicly available search engine database, search queries potentially related to influenza over the corresponding period were identified. An SVM regression model was built to be used for predictions, and the choice of three parameters (C, γ, ε) in the SVM regression model was determined by leave-one-out cross-validation (LOOCV) during the model construction process. The model’s performance was evaluated by the evaluation metrics including Root Mean Square Error, Root Mean Square Percentage Error and Mean Absolute Percentage Error. RESULTS: In total, 17 search queries related to influenza were generated through the initial query selection approach and were adopted to construct the SVM regression model, including nine queries in the same month, three queries at a lag of one month, one query at a lag of two months and four queries at a lag of three months. The SVM model performed well when with the parameters (C = 2, γ = 0.005, ɛ = 0.0001), based on the ensemble data integrating the influenza surveillance data and Baidu search query data. CONCLUSIONS: The results demonstrated the feasibility of using internet search engine query data as the complementary data source for influenza surveillance and the efficiency of SVM regression model in tracking the influenza epidemics in Liaoning.",2018 Jun 25,"['Liang, Feng', 'Guan, Peng', 'Wu, Wei', 'Huang, Desheng']",PeerJ,,,True
b5b3d491ce72ba843d589539a807b0cf32946849,PMC,"Triclosan and triclocarban exposure, infectious disease symptoms and antibiotic prescription in infants—A community-based randomized intervention",http://dx.doi.org/10.1371/journal.pone.0199298,PMC6023107,29953463,CC BY,"BACKGROUND: Triclosan and triclocarban (TCs) are broad-spectrum antimicrobials that, until recently, were found in a wide variety of household and personal wash products. Popular with consumers, TCs have not been shown to protect against infectious diseases. OBJECTIVES: To determine whether use of TC-containing wash products reduces incidence of infection in children less than one year of age. METHODS: Starting in 2011, we nested a randomized intervention of wash products with and without TCs within a multiethnic birth cohort. Maternal reports of infectious disease symptoms and antibiotic use were collected weekly by automated survey; household visits occurred every four months. Antibiotic prescriptions were identified by medical chart review. Urinary triclosan levels were measured in a participant subset. Differences by intervention group in reported infectious disease (primary outcome) and antibiotic use (secondary outcome) were assessed using mixed effects logistic regression and Fisher’s Exact tests, respectively. RESULTS: Infectious illness occurred in 6% of weeks, with upper respiratory illness the predominant syndrome. Among 60 (45%) TC-exposed and 73 (55%) non-TC-exposed babies, infectious disease reports did not differ in frequency between groups (likelihood ratio test: p = 0.88). Medical visits with antibiotic prescriptions were less common in the TC group than in the non-TC group (7.8% vs. 16.6%, respectively; p = 0.02). CONCLUSIONS: Although randomization to TC-containing wash products was not associated with decreased infectious disease reports by mothers, TCs were associated with decreased antibiotic prescriptions, suggesting a benefit against bacterial infection. The recent removal of TCs from consumer wash products makes further elucidation of benefits and risks impracticable.",2018 Jun 28,"['Ley, Catherine', 'Sundaram, Vandana', 'Sanchez, Maria de la Luz', 'Desai, Manisha', 'Parsonnet, Julie']",PLoS One,,,True
08207f16550a3ec7c8e304aa6f1d2f0a61a96982,PMC,"Triclosan and triclocarban exposure, infectious disease symptoms and antibiotic prescription in infants—A community-based randomized intervention",http://dx.doi.org/10.1371/journal.pone.0199298,PMC6023107,29953463,CC BY,"BACKGROUND: Triclosan and triclocarban (TCs) are broad-spectrum antimicrobials that, until recently, were found in a wide variety of household and personal wash products. Popular with consumers, TCs have not been shown to protect against infectious diseases. OBJECTIVES: To determine whether use of TC-containing wash products reduces incidence of infection in children less than one year of age. METHODS: Starting in 2011, we nested a randomized intervention of wash products with and without TCs within a multiethnic birth cohort. Maternal reports of infectious disease symptoms and antibiotic use were collected weekly by automated survey; household visits occurred every four months. Antibiotic prescriptions were identified by medical chart review. Urinary triclosan levels were measured in a participant subset. Differences by intervention group in reported infectious disease (primary outcome) and antibiotic use (secondary outcome) were assessed using mixed effects logistic regression and Fisher’s Exact tests, respectively. RESULTS: Infectious illness occurred in 6% of weeks, with upper respiratory illness the predominant syndrome. Among 60 (45%) TC-exposed and 73 (55%) non-TC-exposed babies, infectious disease reports did not differ in frequency between groups (likelihood ratio test: p = 0.88). Medical visits with antibiotic prescriptions were less common in the TC group than in the non-TC group (7.8% vs. 16.6%, respectively; p = 0.02). CONCLUSIONS: Although randomization to TC-containing wash products was not associated with decreased infectious disease reports by mothers, TCs were associated with decreased antibiotic prescriptions, suggesting a benefit against bacterial infection. The recent removal of TCs from consumer wash products makes further elucidation of benefits and risks impracticable.",2018 Jun 28,"['Ley, Catherine', 'Sundaram, Vandana', 'Sanchez, Maria de la Luz', 'Desai, Manisha', 'Parsonnet, Julie']",PLoS One,,,False
6abee5118fbbe76628fddb016d0502e67f86dfd7,PMC,"Triclosan and triclocarban exposure, infectious disease symptoms and antibiotic prescription in infants—A community-based randomized intervention",http://dx.doi.org/10.1371/journal.pone.0199298,PMC6023107,29953463,CC BY,"BACKGROUND: Triclosan and triclocarban (TCs) are broad-spectrum antimicrobials that, until recently, were found in a wide variety of household and personal wash products. Popular with consumers, TCs have not been shown to protect against infectious diseases. OBJECTIVES: To determine whether use of TC-containing wash products reduces incidence of infection in children less than one year of age. METHODS: Starting in 2011, we nested a randomized intervention of wash products with and without TCs within a multiethnic birth cohort. Maternal reports of infectious disease symptoms and antibiotic use were collected weekly by automated survey; household visits occurred every four months. Antibiotic prescriptions were identified by medical chart review. Urinary triclosan levels were measured in a participant subset. Differences by intervention group in reported infectious disease (primary outcome) and antibiotic use (secondary outcome) were assessed using mixed effects logistic regression and Fisher’s Exact tests, respectively. RESULTS: Infectious illness occurred in 6% of weeks, with upper respiratory illness the predominant syndrome. Among 60 (45%) TC-exposed and 73 (55%) non-TC-exposed babies, infectious disease reports did not differ in frequency between groups (likelihood ratio test: p = 0.88). Medical visits with antibiotic prescriptions were less common in the TC group than in the non-TC group (7.8% vs. 16.6%, respectively; p = 0.02). CONCLUSIONS: Although randomization to TC-containing wash products was not associated with decreased infectious disease reports by mothers, TCs were associated with decreased antibiotic prescriptions, suggesting a benefit against bacterial infection. The recent removal of TCs from consumer wash products makes further elucidation of benefits and risks impracticable.",2018 Jun 28,"['Ley, Catherine', 'Sundaram, Vandana', 'Sanchez, Maria de la Luz', 'Desai, Manisha', 'Parsonnet, Julie']",PLoS One,,,False
4b17c873588e55b7008c67f000919ca3cc7d5aa1,PMC,"Triclosan and triclocarban exposure, infectious disease symptoms and antibiotic prescription in infants—A community-based randomized intervention",http://dx.doi.org/10.1371/journal.pone.0199298,PMC6023107,29953463,CC BY,"BACKGROUND: Triclosan and triclocarban (TCs) are broad-spectrum antimicrobials that, until recently, were found in a wide variety of household and personal wash products. Popular with consumers, TCs have not been shown to protect against infectious diseases. OBJECTIVES: To determine whether use of TC-containing wash products reduces incidence of infection in children less than one year of age. METHODS: Starting in 2011, we nested a randomized intervention of wash products with and without TCs within a multiethnic birth cohort. Maternal reports of infectious disease symptoms and antibiotic use were collected weekly by automated survey; household visits occurred every four months. Antibiotic prescriptions were identified by medical chart review. Urinary triclosan levels were measured in a participant subset. Differences by intervention group in reported infectious disease (primary outcome) and antibiotic use (secondary outcome) were assessed using mixed effects logistic regression and Fisher’s Exact tests, respectively. RESULTS: Infectious illness occurred in 6% of weeks, with upper respiratory illness the predominant syndrome. Among 60 (45%) TC-exposed and 73 (55%) non-TC-exposed babies, infectious disease reports did not differ in frequency between groups (likelihood ratio test: p = 0.88). Medical visits with antibiotic prescriptions were less common in the TC group than in the non-TC group (7.8% vs. 16.6%, respectively; p = 0.02). CONCLUSIONS: Although randomization to TC-containing wash products was not associated with decreased infectious disease reports by mothers, TCs were associated with decreased antibiotic prescriptions, suggesting a benefit against bacterial infection. The recent removal of TCs from consumer wash products makes further elucidation of benefits and risks impracticable.",2018 Jun 28,"['Ley, Catherine', 'Sundaram, Vandana', 'Sanchez, Maria de la Luz', 'Desai, Manisha', 'Parsonnet, Julie']",PLoS One,,,False
95bd6a3d04bd47a4a7683ea948e6de05125a34c6,PMC,"Triclosan and triclocarban exposure, infectious disease symptoms and antibiotic prescription in infants—A community-based randomized intervention",http://dx.doi.org/10.1371/journal.pone.0199298,PMC6023107,29953463,CC BY,"BACKGROUND: Triclosan and triclocarban (TCs) are broad-spectrum antimicrobials that, until recently, were found in a wide variety of household and personal wash products. Popular with consumers, TCs have not been shown to protect against infectious diseases. OBJECTIVES: To determine whether use of TC-containing wash products reduces incidence of infection in children less than one year of age. METHODS: Starting in 2011, we nested a randomized intervention of wash products with and without TCs within a multiethnic birth cohort. Maternal reports of infectious disease symptoms and antibiotic use were collected weekly by automated survey; household visits occurred every four months. Antibiotic prescriptions were identified by medical chart review. Urinary triclosan levels were measured in a participant subset. Differences by intervention group in reported infectious disease (primary outcome) and antibiotic use (secondary outcome) were assessed using mixed effects logistic regression and Fisher’s Exact tests, respectively. RESULTS: Infectious illness occurred in 6% of weeks, with upper respiratory illness the predominant syndrome. Among 60 (45%) TC-exposed and 73 (55%) non-TC-exposed babies, infectious disease reports did not differ in frequency between groups (likelihood ratio test: p = 0.88). Medical visits with antibiotic prescriptions were less common in the TC group than in the non-TC group (7.8% vs. 16.6%, respectively; p = 0.02). CONCLUSIONS: Although randomization to TC-containing wash products was not associated with decreased infectious disease reports by mothers, TCs were associated with decreased antibiotic prescriptions, suggesting a benefit against bacterial infection. The recent removal of TCs from consumer wash products makes further elucidation of benefits and risks impracticable.",2018 Jun 28,"['Ley, Catherine', 'Sundaram, Vandana', 'Sanchez, Maria de la Luz', 'Desai, Manisha', 'Parsonnet, Julie']",PLoS One,,,True
e8fdad25eff3afb451c3d0d95f11cc4225b84895,PMC,"Triclosan and triclocarban exposure, infectious disease symptoms and antibiotic prescription in infants—A community-based randomized intervention",http://dx.doi.org/10.1371/journal.pone.0199298,PMC6023107,29953463,CC BY,"BACKGROUND: Triclosan and triclocarban (TCs) are broad-spectrum antimicrobials that, until recently, were found in a wide variety of household and personal wash products. Popular with consumers, TCs have not been shown to protect against infectious diseases. OBJECTIVES: To determine whether use of TC-containing wash products reduces incidence of infection in children less than one year of age. METHODS: Starting in 2011, we nested a randomized intervention of wash products with and without TCs within a multiethnic birth cohort. Maternal reports of infectious disease symptoms and antibiotic use were collected weekly by automated survey; household visits occurred every four months. Antibiotic prescriptions were identified by medical chart review. Urinary triclosan levels were measured in a participant subset. Differences by intervention group in reported infectious disease (primary outcome) and antibiotic use (secondary outcome) were assessed using mixed effects logistic regression and Fisher’s Exact tests, respectively. RESULTS: Infectious illness occurred in 6% of weeks, with upper respiratory illness the predominant syndrome. Among 60 (45%) TC-exposed and 73 (55%) non-TC-exposed babies, infectious disease reports did not differ in frequency between groups (likelihood ratio test: p = 0.88). Medical visits with antibiotic prescriptions were less common in the TC group than in the non-TC group (7.8% vs. 16.6%, respectively; p = 0.02). CONCLUSIONS: Although randomization to TC-containing wash products was not associated with decreased infectious disease reports by mothers, TCs were associated with decreased antibiotic prescriptions, suggesting a benefit against bacterial infection. The recent removal of TCs from consumer wash products makes further elucidation of benefits and risks impracticable.",2018 Jun 28,"['Ley, Catherine', 'Sundaram, Vandana', 'Sanchez, Maria de la Luz', 'Desai, Manisha', 'Parsonnet, Julie']",PLoS One,,,False
f7f777762bb321537ae1eafaeb630ebcd379a500,PMC,"Triclosan and triclocarban exposure, infectious disease symptoms and antibiotic prescription in infants—A community-based randomized intervention",http://dx.doi.org/10.1371/journal.pone.0199298,PMC6023107,29953463,CC BY,"BACKGROUND: Triclosan and triclocarban (TCs) are broad-spectrum antimicrobials that, until recently, were found in a wide variety of household and personal wash products. Popular with consumers, TCs have not been shown to protect against infectious diseases. OBJECTIVES: To determine whether use of TC-containing wash products reduces incidence of infection in children less than one year of age. METHODS: Starting in 2011, we nested a randomized intervention of wash products with and without TCs within a multiethnic birth cohort. Maternal reports of infectious disease symptoms and antibiotic use were collected weekly by automated survey; household visits occurred every four months. Antibiotic prescriptions were identified by medical chart review. Urinary triclosan levels were measured in a participant subset. Differences by intervention group in reported infectious disease (primary outcome) and antibiotic use (secondary outcome) were assessed using mixed effects logistic regression and Fisher’s Exact tests, respectively. RESULTS: Infectious illness occurred in 6% of weeks, with upper respiratory illness the predominant syndrome. Among 60 (45%) TC-exposed and 73 (55%) non-TC-exposed babies, infectious disease reports did not differ in frequency between groups (likelihood ratio test: p = 0.88). Medical visits with antibiotic prescriptions were less common in the TC group than in the non-TC group (7.8% vs. 16.6%, respectively; p = 0.02). CONCLUSIONS: Although randomization to TC-containing wash products was not associated with decreased infectious disease reports by mothers, TCs were associated with decreased antibiotic prescriptions, suggesting a benefit against bacterial infection. The recent removal of TCs from consumer wash products makes further elucidation of benefits and risks impracticable.",2018 Jun 28,"['Ley, Catherine', 'Sundaram, Vandana', 'Sanchez, Maria de la Luz', 'Desai, Manisha', 'Parsonnet, Julie']",PLoS One,,,False
2ab40cd143985f0fe1f581a31c3aa4009e94e759,PMC,Accuracy of dengue clinical diagnosis with and without NS1 antigen rapid test: Comparison between human and Bayesian network model decision,http://dx.doi.org/10.1371/journal.pntd.0006573,PMC6023245,29912875,CC BY,"Differentiating dengue patients from other acute febrile illness patients is a great challenge among physicians. Several dengue diagnosis methods are recommended by WHO. The application of specific laboratory tests is still limited due to high cost, lack of equipment, and uncertain validity. Therefore, clinical diagnosis remains a common practice especially in resource limited settings. Bayesian networks have been shown to be a useful tool for diagnostic decision support. This study aimed to construct Bayesian network models using basic demographic, clinical, and laboratory profiles of acute febrile illness patients to diagnose dengue. Data of 397 acute undifferentiated febrile illness patients who visited the fever clinic of the Bangkok Hospital for Tropical Diseases, Thailand, were used for model construction and validation. The two best final models were selected: one with and one without NS1 rapid test result. The diagnostic accuracy of the models was compared with that of physicians on the same set of patients. The Bayesian network models provided good diagnostic accuracy of dengue infection, with ROC AUC of 0.80 and 0.75 for models with and without NS1 rapid test result, respectively. The models had approximately 80% specificity and 70% sensitivity, similar to the diagnostic accuracy of the hospital’s fellows in infectious disease. Including information on NS1 rapid test improved the specificity, but reduced the sensitivity, both in model and physician diagnoses. The Bayesian network model developed in this study could be useful to assist physicians in diagnosing dengue, particularly in regions where experienced physicians and laboratory confirmation tests are limited.",2018 Jun 18,"['Sa-ngamuang, Chaitawat', 'Haddawy, Peter', 'Luvira, Viravarn', 'Piyaphanee, Watcharapong', 'Iamsirithaworn, Sopon', 'Lawpoolsri, Saranath']",PLoS Negl Trop Dis,,,True
6191082ec9ddfe582a3ba67622a638c0ed353bde,PMC,Surviving Deadly Lung Infections: Innate Host Tolerance Mechanisms in the Pulmonary System,http://dx.doi.org/10.3389/fimmu.2018.01421,PMC6024012,29988424,CC BY,"Much research on infectious diseases focuses on clearing the pathogen through the use of antimicrobial drugs, the immune response, or a combination of both. Rapid clearance of pathogens allows for a quick return to a healthy state and increased survival. Pathogen-targeted approaches to combating infection have inherent limitations, including their pathogen-specific nature, the potential for antimicrobial resistance, and poor vaccine efficacy, among others. Another way to survive an infection is to tolerate the alterations to homeostasis that occur during a disease state through a process called host tolerance or resilience, which is independent from pathogen burden. Alterations in homeostasis during infection are numerous and include tissue damage, increased inflammation, metabolic changes, temperature changes, and changes in respiration. Given its importance and sensitivity, the lung is a good system for understanding host tolerance to infectious disease. Pneumonia is the leading cause of death for children under five worldwide. One reason for this is because when the pulmonary system is altered dramatically it greatly impacts the overall health and survival of a patient. Targeting host pathways involved in maintenance of pulmonary host tolerance during infection could provide an alternative therapeutic avenue that may be broadly applicable across a variety of pathologies. In this review, we will summarize recent findings on tolerance to host lung infection. We will focus on the involvement of innate immune responses in tolerance and how an initial viral lung infection may alter tolerance mechanisms in leukocytic, epithelial, and endothelial compartments to a subsequent bacterial infection. By understanding tolerance mechanisms in the lung we can better address treatment options for deadly pulmonary infections.",2018 Jun 22,"['Crane, Meredith J.', 'Lee, Kayla M.', 'FitzGerald, Ethan S.', 'Jamieson, Amanda M.']",Front Immunol,,,True
3f3e46abb51fffc3d562bd26117eed795c3febe6,PMC,Baculovirus Surface Display of Immunogenic Proteins for Vaccine Development,http://dx.doi.org/10.3390/v10060298,PMC6024371,29857561,CC BY,"Vaccination is an efficient way to prevent the occurrence of many infectious diseases in humans. To date, several viral vectors have been utilized for the generation of vaccines. Among them, baculovirus—categorized as a nonhuman viral vector—has been used in wider applications. Its versatile features, like large cloning capacity, nonreplicative nature in mammalian cells, and broad tissue tropism, hold it at an excellent position among vaccine vectors. In addition to ease and safety during swift production, recent key improvements to existing baculovirus vectors (such as inclusion of hybrid promoters, immunostimulatory elements, etc.) have led to significant improvements in immunogenicity and efficacy of surface-displayed antigens. Furthermore, some promising preclinical results have been reported that mirror the scope and practicality of baculovirus as a vaccine vector for human applications in the near future. Herein, this review provides an overview of the induced immune responses by baculovirus surface-displayed vaccines against influenza and other infectious diseases in animal models, and highlights the strategies applied to enhance the protective immune responses against the displayed antigens.",2018 May 31,"['Premanand, Balraj', 'Zhong Wee, Poh', 'Prabakaran, Mookkan']",Viruses,,,True
36c6a493ce71b4e2df91b9b486cc847833a4ed25,PMC,Enteric Virus Diversity Examined by Molecular Methods in Brazilian Poultry Flocks,http://dx.doi.org/10.3390/vetsci5020038,PMC6024555,29596389,CC BY,"Enteric viruses play an important role in the Brazilian poultry industry due to the economic impact of resulting low yields of broilers, layers, and breeders. The most common enteric viruses affecting commercial flocks in Brazil include Fowl Adenovirus of group I (FAdV-I), Chicken Parvovirus (ChPV), Chicken Astrovirus (CAstV), Avian Nephritis Virus (ANV), Infectious Bronchitis Virus (IBV), Avian Reovirus (AReo), and Avian Rotavirus (ARtV). The aim of this study was to identify single and multiple infections using data obtained from 270 samples from eleven Brazilian states, corresponding to the period between 2010 and 2017. This was accompanied by an analysis of the relationship between the age of birds, clinical signs, and geographical distribution, using Polymerase Chain Reaction (PCR) and Reverse Transcription-PCR (RT-PCR) techniques. Twenty-five profiles of virus combinations were detected. Single infections were encountered in 86.3% of samples, and multiple infections were present in the remaining 13.7%. Both single and multiple infections affected all kinds of commercial chickens with digestive problems, stunting syndrome, decreases in egg and meat production, increased mortality, and respiratory signs. FAdV-I, ChPV, CAstV, ANV, and ARtV were mostly detected in young broilers, in contrast with IBV, which was detected in hens from one to greater than 51 weeks of age. These results exhibit the complexity of enteric diseases and the still poorly understood role of each pathogen as a unique etiological agent.",2018 Mar 29,"['De la Torre, David I.', 'Nuñez, Luis F.', 'Astolfi-Ferreira, Claudete S.', 'Piantino Ferreira, Antonio J.']",Vet Sci,,,True
cdf75a14256bbd7d9cd72634c174cb4e63c06a25,PMC,Visualizing Viral Infection In Vivo by Multi-Photon Intravital Microscopy,http://dx.doi.org/10.3390/v10060337,PMC6024644,29925766,CC BY,"Viral pathogens have adapted to the host organism to exploit the cellular machinery for virus replication and to modulate the host cells for efficient systemic dissemination and immune evasion. Much of our knowledge of the effects that virus infections have on cells originates from in vitro imaging studies using experimental culture systems consisting of cell lines and primary cells. Recently, intravital microscopy using multi-photon excitation of fluorophores has been applied to observe virus dissemination and pathogenesis in real-time under physiological conditions in living organisms. Critical steps during viral infection and pathogenesis could be studied by direct visualization of fluorescent virus particles, virus-infected cells, and the immune response to viral infection. In this review, I summarize the latest research on in vivo studies of viral infections using multi-photon intravital microscopy (MP-IVM). Initially, the underlying principle of multi-photon microscopy is introduced and experimental challenges during microsurgical animal preparation and fluorescent labeling strategies for intravital imaging are discussed. I will further highlight recent studies that combine MP-IVM with optogenetic tools and transcriptional analysis as a powerful approach to extend the significance of in vivo imaging studies of viral pathogens.",2018 Jun 20,"Sewald, Xaver",Viruses,,,True
756448c2d7dda1e89c0ea4acf6ccd5e2ee02517e,PMC,The Interplay of Viral and Host Factors in Chikungunya Virus Infection: Targets for Antiviral Strategies,http://dx.doi.org/10.3390/v10060294,PMC6024654,29849008,CC BY,"Chikungunya virus (CHIKV) has re-emerged as one of the many medically important arboviruses that have spread rampantly across the world in the past decade. Infected patients come down with acute fever and rashes, and a portion of them suffer from both acute and chronic arthralgia. Currently, there are no targeted therapeutics against this debilitating virus. One approach to develop potential therapeutics is by understanding the viral-host interactions. However, to date, there has been limited research undertaken in this area. In this review, we attempt to briefly describe and update the functions of the different CHIKV proteins and their respective interacting host partners. In addition, we also survey the literature for other reported host factors and pathways involved during CHIKV infection. There is a pressing need for an in-depth understanding of the interaction between the host environment and CHIKV in order to generate potential therapeutics.",2018 May 30,"['Wong, Kai Zhi', 'Chu, Justin Jang Hann']",Viruses,,,True
85d80ad717017002446bd0be2d5f369096c31517,PMC,Live Bacterial Vectors—A Promising DNA Vaccine Delivery System,http://dx.doi.org/10.3390/medsci6020027,PMC6024733,29570602,CC BY,"Vaccination is one of the most successful immunology applications that has considerably improved human health. The DNA vaccine is a new vaccine being developed since the early 1990s. Although the DNA vaccine is promising, no human DNA vaccine has been approved to date. The main problem facing DNA vaccine efficacy is the lack of a DNA vaccine delivery system. Several studies explored this limitation. One of the best DNA vaccine delivery systems uses a live bacterial vector as the carrier. The live bacterial vector induces a robust immune response due to its natural characteristics that are recognized by the immune system. Moreover, the route of administration used by the live bacterial vector is through the mucosal route that beneficially induces both mucosal and systemic immune responses. The mucosal route is not invasive, making the vaccine easy to administer, increasing the patient’s acceptance. Lactic acid bacterium is one of the most promising bacteria used as a live bacterial vector. However, some other attenuated pathogenic bacteria, such as Salmonella spp. and Shigella spp., have been used as DNA vaccine carriers. Numerous studies showed that live bacterial vectors are a promising candidate to deliver DNA vaccines.",2018 Mar 23,"Yurina, Valentina",Med Sci (Basel),,,True
fcc20c80be8954f1682993217bbd2a78659a16f1,PMC,Saracatinib Inhibits Middle East Respiratory Syndrome-Coronavirus Replication In Vitro,http://dx.doi.org/10.3390/v10060283,PMC6024778,29795047,CC BY,"The Middle East respiratory syndrome-coronavirus (MERS-CoV), first identified in Saudi Arabia, is an emerging zoonotic pathogen that causes severe acute respiratory illness in humans with a high fatality rate. Since its emergence, MERS-CoV continues to spread to countries outside of the Arabian Peninsula and gives rise to sporadic human infections following the entry of infected individuals to other countries, which can precipitate outbreaks similar to the one that occurred in South Korea in 2015. Current therapeutics against MERS-CoV infection have primarily been adapted from previous drugs used for the treatment of severe acute respiratory syndrome. In search of new potential drug candidates, we screened a library composed of 2334 clinically approved drugs and pharmacologically active compounds. The drug saracatinib, a potent inhibitor of Src-family of tyrosine kinases (SFK), was identified as an inhibitor of MERS-CoV replication in vitro. Our results suggest that saracatinib potently inhibits MERS-CoV at the early stages of the viral life cycle in Huh-7 cells, possibly through the suppression of SFK signaling pathways. Furthermore, saracatinib exhibited a synergistic effect with gemcitabine, an anticancer drug with antiviral activity against several RNA viruses. These data indicate that saracatinib alone or in combination with gemcitabine can provide a new therapeutic option for the treatment of MERS-CoV infection.",2018 May 24,"['Shin, Jin Soo', 'Jung, Eunhye', 'Kim, Meehyein', 'Baric, Ralph S.', 'Go, Yun Young']",Viruses,,,True
36b0427a13ea042a9fa66a3c605dcfc540eecf91,PMC,Saracatinib Inhibits Middle East Respiratory Syndrome-Coronavirus Replication In Vitro,http://dx.doi.org/10.3390/v10060283,PMC6024778,29795047,CC BY,"The Middle East respiratory syndrome-coronavirus (MERS-CoV), first identified in Saudi Arabia, is an emerging zoonotic pathogen that causes severe acute respiratory illness in humans with a high fatality rate. Since its emergence, MERS-CoV continues to spread to countries outside of the Arabian Peninsula and gives rise to sporadic human infections following the entry of infected individuals to other countries, which can precipitate outbreaks similar to the one that occurred in South Korea in 2015. Current therapeutics against MERS-CoV infection have primarily been adapted from previous drugs used for the treatment of severe acute respiratory syndrome. In search of new potential drug candidates, we screened a library composed of 2334 clinically approved drugs and pharmacologically active compounds. The drug saracatinib, a potent inhibitor of Src-family of tyrosine kinases (SFK), was identified as an inhibitor of MERS-CoV replication in vitro. Our results suggest that saracatinib potently inhibits MERS-CoV at the early stages of the viral life cycle in Huh-7 cells, possibly through the suppression of SFK signaling pathways. Furthermore, saracatinib exhibited a synergistic effect with gemcitabine, an anticancer drug with antiviral activity against several RNA viruses. These data indicate that saracatinib alone or in combination with gemcitabine can provide a new therapeutic option for the treatment of MERS-CoV infection.",2018 May 24,"['Shin, Jin Soo', 'Jung, Eunhye', 'Kim, Meehyein', 'Baric, Ralph S.', 'Go, Yun Young']",Viruses,,,False
85f48fe473305b86d997f44a5801859364b8952b,PMC,Inhibition of Hepatitis E Virus Spread by the Natural Compound Silvestrol,http://dx.doi.org/10.3390/v10060301,PMC6024817,29865243,CC BY,"Every year, there are about 20 Mio hepatitis E virus (HEV) infections and 60,000 deaths that are associated with HEV worldwide. At the present, there exists no specific therapy for HEV. The natural compound silvestrol has a potent antiviral effect against the (−)-strand RNA-virus Ebola virus, and also against the (+)-strand RNA viruses Corona-, Picorna-, and Zika virus. The inhibitory effect on virus spread is due to an inhibition of the DEAD-box RNA helicase eIF4A, which is required to unwind structured 5′-untranslated regions (UTRs). This leads to an impaired translation of viral RNA. The HEV (+)-strand RNA genome contains a 5′-capped, short 5′-UTR. This study aims to analyze the impact of silvestrol on the HEV life cycle. Persistently infected A549 cells were instrumental. This study identifies silvestrol as a potent inhibitor of the release of HEV infectious viral particles. This goes along with a strongly reduced HEV capsid protein translation, retention of viral RNA inside the cytoplasm, and without major cytotoxic effects. Interestingly, in parallel silvestrol affects the activity of the antiviral major vault protein (MVP) by translocation from the cytoplasm to the perinuclear membrane. These data further characterize the complex antiviral activity of silvestrol and show silvestrol’s broad spectrum of function, since HEV is a virus without complex secondary structures in its genome, but it is still affected.",2018 Jun 2,"['Glitscher, Mirco', 'Himmelsbach, Kiyoshi', 'Woytinek, Kathrin', 'Johne, Reimar', 'Reuter, Andreas', 'Spiric, Jelena', 'Schwaben, Luisa', 'Grünweller, Arnold', 'Hildt, Eberhard']",Viruses,,,True
7633ee09c0059b99608c1cfbeefd19775c0317ff,PMC,Field Efficacy of an Attenuated Infectious Bronchitis Variant 2 Virus Vaccine in Commercial Broiler Chickens,http://dx.doi.org/10.3390/vetsci5020049,PMC6024885,29747397,CC BY,"Egyptian poultry suffer from frequent respiratory disease outbreaks associated with Infectious Bronchitis Virus (IBV) variant 2 strains (Egy/VarII). Different vaccination programs using imported vaccines have failed to protect the flocks from field challenge. Recent studies confirmed a successful protection using homologous strains as live attenuated vaccines. In this study, a newly developed live attenuated IB-VAR2 vaccine representing the GI-23 Middle East IBV lineage was evaluated in day-old commercial broilers in an IBV-endemic area. A commercial broiler flock was vaccinated with the IB-VAR2 vaccine at day-old age followed by IB-H120 at day 16. The vaccinated flock was monitored on a weekly basis till the slaughter age. The health status and growth performance were monitored, and selected viral pathogen real-time RT-PCR (rRT-PCR) detection was conducted on a weekly basis. Finally, the flock was compared to a nearby farm with only the classical IB-H120 vaccination program. Results showed that the IB-VAR2 vaccine was tolerable in day-old broiler chicks. The IBV virus rRT-PCR detection was limited to the trachea as compared to its nephropathogenic parent virus. Respiratory disease problems and high mortalities were reported in the IB-H120-only vaccinated flock. An exposure to a wild-type Egy/VarII strain was confirmed in both flocks as indicated by partial IBV S1 gene sequence. Even though the IB-VAR2-vaccinated flock performance was better than the flock that received only IB-H120, the IBV ELISA (enzyme-linked immunosorbent assay) and log2 Haemagglutination inhibition (HI) antibody mean titers remained high (3128 ± 2713 and ≥9 log2, respectively) until the 28th day of age. The current study demonstrates the safety and effectiveness of IB-VAR2 as a live attenuated vaccine in day-old commercial broilers. Also, the combination of IB-VAR2 and classical IBV vaccines confers a broader protective immune response against IBV in endemic areas.",2018 May 9,"['Elhady, Mohamed A.', 'Ali, Ahmed', 'Kilany, Walid H.', 'Elfeil, Wael K.', 'Ibrahim, Hytham', 'Nabil, Ahmed', 'Samir, Ahmed', 'El Sayed, Magdy']",Vet Sci,,,True
7d150d1f95973b8be18b73ac8e567dabdc049c2a,PMC,Modeling the Heterogeneity of Dengue Transmission in a City,http://dx.doi.org/10.3390/ijerph15061128,PMC6025315,29857503,CC BY,"Dengue fever is one of the most important vector-borne diseases in the world, and modeling its transmission dynamics allows for determining the key influence factors and helps to perform interventions. The heterogeneity of mosquito bites of humans during the spread of dengue virus is an important factor that should be considered when modeling the dynamics. However, traditional models generally assumed homogeneous mixing between humans and vectors, which is inconsistent with reality. In this study, we proposed a compartmental model with negative binomial distribution transmission terms to model this heterogeneity at the population level. By including the aquatic stage of mosquitoes and incorporating the impacts of the environment and climate factors, an extended model was used to simulate the 2014 dengue outbreak in Guangzhou, China, and to simulate the spread of dengue in different scenarios. The results showed that a high level of heterogeneity can result in a small peak size in an outbreak. As the level of heterogeneity decreases, the transmission dynamics approximate the dynamics predicted by the corresponding homogeneous mixing model. The simulation results from different scenarios showed that performing interventions early and decreasing the carrying capacity for mosquitoes are necessary for preventing and controlling dengue epidemics. This study contributes to a better understanding of the impact of heterogeneity during the spread of dengue virus.",2018 Jun 31,"['Kong, Lingcai', 'Wang, Jinfeng', 'Li, Zhongjie', 'Lai, Shengjie', 'Liu, Qiyong', 'Wu, Haixia', 'Yang, Weizhong']",Int J Environ Res Public Health,,,True
adab31f0d8b09bc7d087969e7664b22ab584dc81,PMC,Infectious Disease Prevalence and Factors Associated with Upper Respiratory Infection in Cats Following Relocation,http://dx.doi.org/10.3390/ani8060091,PMC6025414,29890718,CC BY,"SIMPLE SUMMARY: Relocation of cats and kittens is a relatively new practice in animal welfare. It is one of the many tools used by animal welfare agencies to decrease shelter euthanasia rates across the country. However, there are few and sometimes conflicting guidelines for either minimum standards or best practices regarding relocation programs. Most operational practices are evolving and are often based on lessons learned. Concerns about the frequency of infectious diseases and the corresponding likelihood of spread are commonly raised in the context of animal relocation. In this study, which followed one relocation program over a 7-month period, highly contagious infectious diseases, feline panleukopenia virus (FPV) and ringworm, were uncommon in cats following relocation into one shelter. Upper respiratory infection (URI) was, however, relatively more frequent with younger age, increased time in transport during relocation and increased time spent at the shelter following relocation all associated with increased disease frequency. Accordingly, even in an established relocation program, steps should be taken to mitigate the risk of upper respiratory infection in relocated cats. ABSTRACT: Feline relocation is used increasingly in animal welfare to decrease shelter euthanasia rates and increase positive outcomes. Concerns about infectious disease introduction and transmission are often expressed; however, little research has been conducted on even the baseline prevalence of infectious disease following relocation. This study, which collected data on 430 cats relocated through an established program over 7 months, evaluated the prevalence of upper respiratory infection (URI), feline panleukopenia virus (FPV) and dermatophytosis at one destination agency. The period prevalence was 25.8% for URI, 1.6% for FPV and 0.9% for dermatophytosis. Mixed-effects logistic regression was performed to investigate factors associated with URI. Younger age, increased time in transport, and increased length of stay at the destination agency were associated with increased URI prevalence following relocation. The findings of this study reveal that certain highly contagious and environmentally persistent infectious diseases, such as FPV and dermatophytosis, are uncommon following relocation in an established program; however, URI in relocated cats should be proactively managed. Animal welfare agencies can use this information to guide shelter and relocation operations and mitigate the impact of URI in relocated cats.",2018 Jun 9,"['Aziz, Mehnaz', 'Janeczko, Stephanie', 'Gupta, Maya']",Animals (Basel),,,True
3b6d78d18468508dd0b85bc9fc2e1b2e3079ec05,PMC,Exploring the Determinants of Perceived Risk of Middle East Respiratory Syndrome (MERS) in Korea,http://dx.doi.org/10.3390/ijerph15061168,PMC6025578,29867054,CC BY,"The world is turning into a risky society. Although modernization based on the developments in science and technology has increased individuals’ well-being and wealth, the perceived risk toward the complex technological system has increased. In a risky society, social accidents amplify the existing fear among individuals. It is generally assumed that each value, perception, and resource influences the fear of risk. However, very few studies have tested these three factors together within an integrated causal model. Therefore, the present study aimed to examine the determinants that influence the perceived risk in cases of Middle East Respiratory Syndrome (MERS), a deadly epidemic disease, in Korea. Based on the theoretical model, we analyzed the survey data collected from respondents (N = 814) in Korea. After controlling for variables such as sociodemographic characteristics, we examined how three competing factors, i.e., value, perception, and resource, influence the perceived risk of MERS. The analysis showed that trust and vulnerability variables in the perception factor, health state, and perceived knowledge in the resource factor had a significant impact on the perceived risk of MERS.",2018 Jun 4,"['Kim, Sunhee', 'Kim, Seoyong']",Int J Environ Res Public Health,,,True
eff8bed68ef6109e8f0c51a8b1ec4b6ca5b6329e,PMC,Nanopore sequencing as a revolutionary diagnostic tool for porcine viral enteric disease complexes identifies porcine kobuvirus as an important enteric virus,http://dx.doi.org/10.1038/s41598-018-28180-9,PMC6026206,29959349,CC BY,"Enteric diseases in swine are often caused by different pathogens and thus metagenomics are a useful tool for diagnostics. The capacities of nanopore sequencing for viral diagnostics were investigated here. First, cell culture-grown porcine epidemic diarrhea virus and rotavirus A were pooled and sequenced on a MinION. Reads were already detected at 7 seconds after start of sequencing, resulting in high sequencing depths (19.2 to 103.5X) after 3 h. Next, diarrheic feces of a one-week-old piglet was analyzed. Almost all reads (99%) belonged to bacteriophages, which may have reshaped the piglet’s microbiome. Contigs matched Bacteroides, Escherichia and Enterococcus phages. Moreover, porcine kobuvirus was discovered in the feces for the first time in Belgium. Suckling piglets shed kobuvirus from one week of age, but an association between peak of viral shedding (10(6.42)–10(7.01) copies/swab) and diarrheic signs was not observed during a follow-up study. Retrospective analysis showed the widespread (n = 25, 56.8% positive) of genetically moderately related kobuviruses among Belgian diarrheic piglets. MinION enables rapid detection of enteric viruses. Such new methodologies will change diagnostics, but more extensive validations should be conducted. The true enteric pathogenicity of porcine kobuvirus should be questioned, while its subclinical importance cannot be excluded.",2018 Jun 29,"['Theuns, Sebastiaan', 'Vanmechelen, Bert', 'Bernaert, Quinten', 'Deboutte, Ward', 'Vandenhole, Marilou', 'Beller, Leen', 'Matthijnssens, Jelle', 'Maes, Piet', 'Nauwynck, Hans J.']",Sci Rep,,,True
ead34dbe8d24c80ca48b9f828aa34be52a65a8a6,PMC,"Comparison of Infant Gut and Skin Microbiota, Resistome and Virulome Between Neonatal Intensive Care Unit (NICU) Environments",http://dx.doi.org/10.3389/fmicb.2018.01361,PMC6026636,29988506,CC BY,"Background: There is a growing move to provide care for premature infants in a single family, private room neonatal intensive care unit (NICU) in place of the traditional shared space, open bay NICU. The resultant effect on the developing neonatal microbiota is unknown. Study Design: Stool and groin skin swabs were collected from infants in a shared-space NICU (old NICU) and a single-family room NICU (new NICU) on the same hospital campus. Metagenomic sequencing was performed and data analyzed by CosmosID bioinformatics software package. Results: There were no significant differences between the cohorts in gestational age, length of stay, and delivery mode; infants in the old NICU received significantly more antibiotics (p = 0.03). Differentially abundant antimicrobial resistance genes and virulence associated genes were found between the cohorts in stool and skin, with more differentially abundant antimicrobial resistance genes in the new NICU. The entire bacterial microbiota analyzed to the genus level significantly differed between cohorts in skin (p = 0.0001) but not in stool samples. There was no difference in alpha diversity between the two cohorts. DNA viruses and fungi were detected but did not differ between cohorts. Conclusion: Differences were seen in the resistome and virulome between the two cohorts with more differentially abundant antimicrobial resistance genes in the new NICU. This highlights the influence that different NICU environments can have on the neonatal microbiota. Whether the differences were due to the new NICU being a single-family NICU or located in a newly constructed building warrants exploration. Long term health outcomes from the differences observed must be followed longitudinally.",2018 Jun 25,"['Hourigan, Suchitra K.', 'Subramanian, Poorani', 'Hasan, Nur A.', 'Ta, Allison', 'Klein, Elisabeth', 'Chettout, Nassim', 'Huddleston, Kathi', 'Deopujari, Varsha', 'Levy, Shira', 'Baveja, Rajiv', 'Clemency, Nicole C.', 'Baker, Robin L.', 'Niederhuber, John E.', 'Colwell, Rita R.']",Front Microbiol,,,True
745f78dadf6e5a2feb79900688cd5fb9ead4d72e,PMC,Evaluation of Anti-Toxoplasma gondii Effect of Ursolic Acid as a Novel Toxoplasmosis Inhibitor,http://dx.doi.org/10.3390/ph11020043,PMC6026977,29747388,CC BY,"This study was carried out to evaluate the anti-parasitic effect of ursolic acid against Toxoplasma gondii (T. gondii) that induces toxoplasmosis, particularly in humans. The anti-parasitic effects of ursolic acid against T. gondii-infected cells and T. gondii were evaluated through different specific assays, including immunofluorescence staining and animal testing. Ursolic acid effectively inhibited the proliferation of T. gondii when compared with sulfadiazine, and consistently induced anti-T. gondii activity/effect. In particular, the formation of parasitophorous vacuole membrane (PVM) in host cells was markedly decreased after treating ursolic acid, which was effectively suppressed. Moreover, the survival rate of T. gondii was strongly inhibited in T. gondii group treated with ursolic acid, and then 50% inhibitory concentration (IC(50)) against T. gondii was measured as 94.62 μg/mL. The T. gondii-infected mice treated with ursolic acid indicated the same survival rates and activity as the normal group. These results demonstrate that ursolic acid causes anti-T. gondii action and effect by strongly blocking the proliferation of T. gondii through the direct and the selective T. gondii-inhibitory ability as well as increases the survival of T. gondii-infected mice. This study shows that ursolic acid has the potential to be used as a promising anti-T. gondii candidate substance for developing effective anti-parasitic drugs.",2018 May 9,"['Choi, Won Hyung', 'Lee, In Ah']",Pharmaceuticals (Basel),,,True
925782695d6de40cdf2d0e94622ce06d277ccf74,PMC,"Genome Characterization of a Pathogenic Porcine Rotavirus B Strain Identified in Buryat Republic, Russia in 2015",http://dx.doi.org/10.3390/pathogens7020046,PMC6027140,29677111,CC BY,"An outbreak of enteric disease of unknown etiology with 60% morbidity and 8% mortality in weaning piglets occurred in November 2015 on a farm in Buryat Republic, Russia. Metagenomic sequencing revealed the presence of rotavirus B in feces from diseased piglets while no other pathogens were identified. Clinical disease was reproduced in experimentally infected piglets, yielding the 11 RVB gene segments for strain Buryat15, with an RVB genotype constellation of G12-P[4]-I13-R4-C4-M4-A8-N10-T4-E4-H7. This genotype constellation has also been identified in the United States. While the Buryat15 VP7 protein lacked unique amino acid differences in the predicted neutralizing epitopes compared to the previously published swine RVB G12 strains, this report of RVB in Russian swine increases our epidemiological knowledge on the global prevalence and genetic diversity of RVB.",2018 Apr 20,"['Alekseev, Konstantin P.', 'Penin, Aleksey A.', 'Mukhin, Alexey N.', 'Khametova, Kizkhalum M.', 'Grebennikova, Tatyana V.', 'Yuzhakov, Anton G.', 'Moskvina, Anna S.', 'Musienko, Maria I.', 'Raev, Sergey A.', 'Mishin, Alexandr M.', 'Kotelnikov, Alexandr P.', 'Verkhovsky, Oleg A.', 'Aliper, Taras I.', 'Nepoklonov, Eugeny A.', 'Herrera-Ibata, Diana M.', 'Shepherd, Frances K.', 'Marthaler, Douglas G.']",Pathogens,,,True
f8e22f8898bd3316fd2f3dd85fe8395ec1182fab,PMC,"Genome Characterization of a Pathogenic Porcine Rotavirus B Strain Identified in Buryat Republic, Russia in 2015",http://dx.doi.org/10.3390/pathogens7020046,PMC6027140,29677111,CC BY,"An outbreak of enteric disease of unknown etiology with 60% morbidity and 8% mortality in weaning piglets occurred in November 2015 on a farm in Buryat Republic, Russia. Metagenomic sequencing revealed the presence of rotavirus B in feces from diseased piglets while no other pathogens were identified. Clinical disease was reproduced in experimentally infected piglets, yielding the 11 RVB gene segments for strain Buryat15, with an RVB genotype constellation of G12-P[4]-I13-R4-C4-M4-A8-N10-T4-E4-H7. This genotype constellation has also been identified in the United States. While the Buryat15 VP7 protein lacked unique amino acid differences in the predicted neutralizing epitopes compared to the previously published swine RVB G12 strains, this report of RVB in Russian swine increases our epidemiological knowledge on the global prevalence and genetic diversity of RVB.",2018 Apr 20,"['Alekseev, Konstantin P.', 'Penin, Aleksey A.', 'Mukhin, Alexey N.', 'Khametova, Kizkhalum M.', 'Grebennikova, Tatyana V.', 'Yuzhakov, Anton G.', 'Moskvina, Anna S.', 'Musienko, Maria I.', 'Raev, Sergey A.', 'Mishin, Alexandr M.', 'Kotelnikov, Alexandr P.', 'Verkhovsky, Oleg A.', 'Aliper, Taras I.', 'Nepoklonov, Eugeny A.', 'Herrera-Ibata, Diana M.', 'Shepherd, Frances K.', 'Marthaler, Douglas G.']",Pathogens,,,False
aef8022f38dee0b0eadc00eb8a955384b87f3626,PMC,Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine,http://dx.doi.org/10.3390/vaccines6020018,PMC6027237,29587436,CC BY,"Next-generation vaccines that utilize T cells could potentially overcome the limitations of current influenza vaccines that rely on antibodies to provide narrow subtype-specific protection and are prone to antigenic mismatch with circulating strains. Evidence from animal models shows that T cells can provide heterosubtypic protection and are crucial for immune control of influenza virus infections. This has provided hope for the design of a universal vaccine able to prime against diverse influenza virus strains and subtypes. However, multiple hurdles exist for the realisation of a universal T cell vaccine. Overall primary concerns are: extrapolating human clinical studies, seeding durable effective T cell resident memory (Trm), population human leucocyte antigen (HLA) coverage, and the potential for T cell-mediated immune escape. Further comprehensive human clinical data is needed during natural infection to validate the protective role T cells play during infection in the absence of antibodies. Furthermore, fundamental questions still exist regarding the site, longevity and duration, quantity, and phenotype of T cells needed for optimal protection. Standardised experimental methods, and eventually simplified commercial assays, to assess peripheral influenza-specific T cell responses are needed for larger-scale clinical studies of T cells as a correlate of protection against influenza infection. The design and implementation of a T cell-inducing vaccine will require a consensus on the level of protection acceptable in the community, which may not provide sterilizing immunity but could protect the individual from severe disease, reduce the length of infection, and potentially reduce transmission in the community. Therefore, increasing the standard of care potentially offered by T cell vaccines should be considered in the context of pandemic preparedness and zoonotic infections, and in combination with improved antibody vaccine targeting methods. Current pandemic vaccine preparedness measures and ongoing clinical trials under-utilise T cell-inducing vaccines, reflecting the myriad questions that remain about how, when, where, and which T cells are needed to fight influenza virus infection. This review aims to bring together basic fundamentals of T cell biology with human clinical data, which need to be considered for the implementation of a universal vaccine against influenza that harnesses the power of T cells.",2018 Mar 26,"['Clemens, E. Bridie', 'van de Sandt, Carolien', 'Wong, Sook San', 'Wakim, Linda M.', 'Valkenburg, Sophie A.']",Vaccines (Basel),,,True
83c2c8a726eb4a9959ecfbba7b491f733b45f425,PMC,Cell-Penetrating Peptides to Enhance Delivery of Oligonucleotide-Based Therapeutics,http://dx.doi.org/10.3390/biomedicines6020051,PMC6027240,29734750,CC BY,"The promise of nucleic acid based oligonucleotides as effective genetic therapies has been held back by their low bioavailability and poor cellular uptake to target tissues upon systemic administration. One such strategy to improve upon delivery is the use of short cell-penetrating peptides (CPPs) that can be either directly attached to their cargo through covalent linkages or through the formation of noncovalent nanoparticle complexes that can facilitate cellular uptake. In this review, we will highlight recent proof-of-principle studies that have utilized both of these strategies to improve nucleic acid delivery and discuss the prospects for translation of this approach for clinical application.",2018 May 5,"['McClorey, Graham', 'Banerjee, Subhashis']",Biomedicines,,,True
479b8abcecf4072618ebe266fb3d47b4b72ea91f,PMC,"The Crosstalk of Endoplasmic Reticulum (ER) Stress Pathways with NF-κB: Complex Mechanisms Relevant for Cancer, Inflammation and Infection",http://dx.doi.org/10.3390/biomedicines6020058,PMC6027367,29772680,CC BY,"Stressful conditions occuring during cancer, inflammation or infection activate adaptive responses that are controlled by the unfolded protein response (UPR) and the nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) signaling pathway. These systems can be triggered by chemical compounds but also by cytokines, toll-like receptor ligands, nucleic acids, lipids, bacteria and viruses. Despite representing unique signaling cascades, new data indicate that the UPR and NF-κB pathways converge within the nucleus through ten major transcription factors (TFs), namely activating transcription factor (ATF)4, ATF3, CCAAT/enhancer-binding protein (CEBP) homologous protein (CHOP), X-box-binding protein (XBP)1, ATF6α and the five NF-κB subunits. The combinatorial occupancy of numerous genomic regions (enhancers and promoters) coordinates the transcriptional activation or repression of hundreds of genes that collectively determine the balance between metabolic and inflammatory phenotypes and the extent of apoptosis and autophagy or repair of cell damage and survival. Here, we also discuss results from genetic experiments and chemical activators of endoplasmic reticulum (ER) stress that suggest a link to the cytosolic inhibitor of NF-κB (IκB)α degradation pathway. These data show that the UPR affects this major control point of NF-κB activation through several mechanisms. Taken together, available evidence indicates that the UPR and NF-κB interact at multiple levels. This crosstalk provides ample opportunities to fine-tune cellular stress responses and could also be exploited therapeutically in the future.",2018 May 16,"['Schmitz, M. Lienhard', 'Shaban, M. Samer', 'Albert, B. Vincent', 'Gökçen, Anke', 'Kracht, Michael']",Biomedicines,,,True
cafa25b00fd0b65e7d337fd03a204be2acb3243f,PMC,Pre-Clinical and Clinical Efficiency of Complexes of Oligoribonucleotides with D-Mannitol against Respiratory Viruses,http://dx.doi.org/10.3390/pharmaceutics10020059,PMC6027485,29783756,CC BY,"Oligoribonucleotides-D-mannitol (ORNs-D-M) complexes possess antiviral, anti-inflammatory, and immunomodulatory actions. The aim of the present study was to evaluated an antiviral effect of ORNs-D-M against parainfluenza virus type 3 (PIV3); influenza CA709, PR834; avian influenza virus H5N2 (AIV) in vitro by a TCID(50); hemadsorption and neuraminidase activity assays; and clinical efficiency of ORNs-D-M in patients with acute respiratory infections (ARIs) of various etiologies by PCR assay and AmpliSens test systems. It was observed that ORNs-D-M have an antiviral activity against the influenza CA709, PR834, PIV3, and AIV in vitro. The injectable dosage form of ORNs-D-M was shown to have a stronger antiviral effect compared to capsule form. It was also detected that the injectable form of ORNs-D-M significantly reduced the neuraminidase activity of influenza PR834. A complex treatment of patients with ORNs-D-M had a positive effect on the course of the disease, it accelerated patients’ recovery. Treatment with ORNs-D-M caused eradication of adeno- and influenza viruses in patients with ARI. This drug contributed to significant decrease in duration of febrile period and cough. Comprehensive treatment with ORNs-D-M improved the disease clinical findings significantly. Collectively, these results suggested that ORNs-D-M may be used at co-infection with influenza and other respiratory viruses as a medical antiviral drug.",2018 May 19,"['Melnichuk, Nataliia', 'Zarubaev, Vladimir', 'Iosyk, Iaryna', 'Andreychyn, Mychaylo', 'Semernikova, Larisa', 'Tkachuk, Zenoviy']",Pharmaceutics,,,True
a1ddcd1a96b072bef649cc450c4bf5bc850a6957,PMC,"Thiopyrano[2,3-d]Thiazoles as New Efficient Scaffolds in Medicinal Chemistry",http://dx.doi.org/10.3390/scipharm86020026,PMC6027677,29903979,CC BY,"This review presents the up to date development of fused thiopyranothiazoles that comprise one of the thiazolidine derivatives classes. Thiazolidine and thiazolidinone-related compounds belong to the widely studied heterocycles from a medicinal chemistry perspective. From the chemical point of view, they are perfect heterodienes to undergo hetero-Diels–Alder reaction with a variety of dienophiles, yielding regio- and diastereoselectively thiopyranothiazole scaffolds. The annealing of thiazole and thiopyran cycles in condensed heterosystem is a precondition for the “centers conservative” creation of the ligand-target binding complex and can promote a potential selectivity to biotargets. The review covers possible therapeutic applications of thiopyrano[2,3-d]thiazoles, such as anti-inflammatory, antibacterial, anticancer as well as aniparasitic activities. Thus, thiopyrano[2,3-d]thiazoles may be used as powerful tools in the development of biologically active agents and drug-like molecules.",2018 Jun 14,"['Kryshchyshyn, Anna', 'Roman, Olexandra', 'Lozynskyi, Andrii', 'Lesyk, Roman']",Sci Pharm,,,True
bdffa5902b25099211f840d9e3b8cc7e16f54632,PMC,CEACAM1 promotes CD8(+) T cell responses and improves control of a chronic viral infection,http://dx.doi.org/10.1038/s41467-018-04832-2,PMC6028648,29967450,CC BY,"Dysfunction of CD8(+) T cells can lead to the development of chronic viral infection. Identifying mechanisms responsible for such T cell dysfunction is therefore of great importance to understand how to prevent persistent viral infection. Here we show using lymphocytic choriomeningitis virus (LCMV) infection that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is fundamental for recruiting lymphocyte-specific protein kinase (Lck) into the T cell receptor complex to form an efficient immunological synapse. CEACAM1 is essential for activation of CD8(+) T cells, and the absence of CEACAM1 on virus-specific CD8(+) T cells limits the antiviral CD8(+) T cell response. Treatment with anti-CEACAM1 antibody stabilizes Lck in the immunological synapse, prevents CD8(+) T cell exhaustion, and improves control of virus infection in vivo. Treatment of human virus-specific CD8(+) T cells with anti-CEACAM1 antibody similarly enhances their proliferation. We conclude that CEACAM1 is an important regulator of virus-specific CD8(+) T cell functions in mice and humans and represents a promising therapeutic target for modulating CD8(+) T cells.",2018 Jul 2,"['Khairnar, Vishal', 'Duhan, Vikas', 'Patil, Ashwini M.', 'Zhou, Fan', 'Bhat, Hilal', 'Thoens, Christine', 'Sharma, Piyush', 'Adomati, Tom', 'Friendrich, Sarah-Kim', 'Bezgovsek, Judith', 'Dreesen, Janine D.', 'Wennemuth, Gunther', 'Westendorf, Astrid M.', 'Zelinskyy, Gennadiy', 'Dittmer, Ulf', 'Hardt, Cornelia', 'Timm, Jörg', 'Göthert, Joachim R.', 'Lang, Philipp A.', 'Singer, Bernhard B.', 'Lang, Karl S.']",Nat Commun,,,False
d9b9b75ee4d554ad43e8a8531af0b6763a1d6652,PMC,CEACAM1 promotes CD8(+) T cell responses and improves control of a chronic viral infection,http://dx.doi.org/10.1038/s41467-018-04832-2,PMC6028648,29967450,CC BY,"Dysfunction of CD8(+) T cells can lead to the development of chronic viral infection. Identifying mechanisms responsible for such T cell dysfunction is therefore of great importance to understand how to prevent persistent viral infection. Here we show using lymphocytic choriomeningitis virus (LCMV) infection that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is fundamental for recruiting lymphocyte-specific protein kinase (Lck) into the T cell receptor complex to form an efficient immunological synapse. CEACAM1 is essential for activation of CD8(+) T cells, and the absence of CEACAM1 on virus-specific CD8(+) T cells limits the antiviral CD8(+) T cell response. Treatment with anti-CEACAM1 antibody stabilizes Lck in the immunological synapse, prevents CD8(+) T cell exhaustion, and improves control of virus infection in vivo. Treatment of human virus-specific CD8(+) T cells with anti-CEACAM1 antibody similarly enhances their proliferation. We conclude that CEACAM1 is an important regulator of virus-specific CD8(+) T cell functions in mice and humans and represents a promising therapeutic target for modulating CD8(+) T cells.",2018 Jul 2,"['Khairnar, Vishal', 'Duhan, Vikas', 'Patil, Ashwini M.', 'Zhou, Fan', 'Bhat, Hilal', 'Thoens, Christine', 'Sharma, Piyush', 'Adomati, Tom', 'Friendrich, Sarah-Kim', 'Bezgovsek, Judith', 'Dreesen, Janine D.', 'Wennemuth, Gunther', 'Westendorf, Astrid M.', 'Zelinskyy, Gennadiy', 'Dittmer, Ulf', 'Hardt, Cornelia', 'Timm, Jörg', 'Göthert, Joachim R.', 'Lang, Philipp A.', 'Singer, Bernhard B.', 'Lang, Karl S.']",Nat Commun,,,True
af086d3b4ac81621820f31c17c8b0796080583ff,PMC,mHealth Technology Use and Implications in Historically Underserved and Minority Populations in the United States: Systematic Literature Review,http://dx.doi.org/10.2196/mhealth.8383,PMC6028762,29914860,CC BY,"BACKGROUND: The proportion of people in the United States who are members of at least two ethnic groups is projected to increase to 10% by the year 2050. This makes addressing health disparities and health inequities in minority populations increasingly more difficult. Minority populations, including those who classify themselves as African American and Hispanic, are using mobile phones to access health information via the internet more frequently than those who classify themselves as white, providing unique opportunities for those in public health and health education to reach these traditionally underserved populations using mobile health (mHealth) interventions. OBJECTIVE: The objective of this review was to assess studies conducted in the United States that have used mHealth tools and strategies to develop and implement interventions in underserved populations. This review also examines the ways in which mHealth strategies are being employed in public health interventions to these priority population groups, as mobile phone capabilities include text messaging, mobile apps, internet access, emails, video streaming, social media, instant messaging, and more. METHODS: A systematic literature review was conducted using key search phrases, the matrix method, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart diagram to identify key studies conducted between the years of 2009-2016 in the United States. These studies were reviewed for their use of mHealth interventions in historically underserved and minority populations. RESULTS: A total of 16,270 articles were initially identified using key search phrases in three databases. Titles were reviewed and articles not meeting criteria were excluded, leaving 156 articles for further review. After additional review for relevance and inclusion criteria, 16 articles were qualified and analyzed. CONCLUSIONS: mHealth is a promising area of development for public health and health education. While successful research has been done using text messaging (short message service, SMS) and other mHealth strategies, there is a need for more research using mobile phones and tablet applications. This literature review demonstrates mHealth technology has the ability to increase prevention and health education in health disparate communities and concludes that more specified research is needed.",2018 Jun 18,"['Anderson-Lewis, Charkarra', 'Darville, Gabrielle', 'Mercado, Rebeccah Eve', 'Howell, Savannah', 'Di Maggio, Samantha']",JMIR Mhealth Uhealth,,,False
cc5db16c1ea08dfd76f08c6fadba8863a3a59c18,PMC,Canine respiratory coronavirus employs caveolin-1-mediated pathway for internalization to HRT-18G cells,http://dx.doi.org/10.1186/s13567-018-0551-9,PMC6029178,29970183,CC BY,"Canine respiratory coronavirus (CRCoV), identified in 2003, is a member of the Coronaviridae family. The virus is a betacoronavirus and a close relative of human coronavirus OC43 and bovine coronavirus. Here, we examined entry of CRCoV into human rectal tumor cells (HRT-18G cell line) by analyzing co-localization of single virus particles with cellular markers in the presence or absence of chemical inhibitors of pathways potentially involved in virus entry. We also targeted these pathways using siRNA. The results show that the virus hijacks caveolin-dependent endocytosis to enter cells via endocytic internalization. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13567-018-0551-9) contains supplementary material, which is available to authorized users.",2018 Jul 3,"['Szczepanski, Artur', 'Owczarek, Katarzyna', 'Milewska, Aleksandra', 'Baster, Zbigniew', 'Rajfur, Zenon', 'Mitchell, Judy A.', 'Pyrc, Krzysztof']",Vet Res,,,False
567cbbb719b238bcd46a7c4de309537911ea42a4,PMC,Canine respiratory coronavirus employs caveolin-1-mediated pathway for internalization to HRT-18G cells,http://dx.doi.org/10.1186/s13567-018-0551-9,PMC6029178,29970183,CC BY,"Canine respiratory coronavirus (CRCoV), identified in 2003, is a member of the Coronaviridae family. The virus is a betacoronavirus and a close relative of human coronavirus OC43 and bovine coronavirus. Here, we examined entry of CRCoV into human rectal tumor cells (HRT-18G cell line) by analyzing co-localization of single virus particles with cellular markers in the presence or absence of chemical inhibitors of pathways potentially involved in virus entry. We also targeted these pathways using siRNA. The results show that the virus hijacks caveolin-dependent endocytosis to enter cells via endocytic internalization. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13567-018-0551-9) contains supplementary material, which is available to authorized users.",2018 Jul 3,"['Szczepanski, Artur', 'Owczarek, Katarzyna', 'Milewska, Aleksandra', 'Baster, Zbigniew', 'Rajfur, Zenon', 'Mitchell, Judy A.', 'Pyrc, Krzysztof']",Vet Res,,,True
0d1448dbed0b123a78907316826d116ad97cfbcf,PMC,Review and Meta-Analyses of TAAR1 Expression in the Immune System and Cancers,http://dx.doi.org/10.3389/fphar.2018.00683,PMC6029583,29997511,CC BY,"Since its discovery in 2001, the major focus of TAAR1 research has been on its role in monoaminergic regulation, drug-induced reward and psychiatric conditions. More recently, TAAR1 expression and functionality in immune system regulation and immune cell activation has become a topic of emerging interest. Here, we review the immunologically-relevant TAAR1 literature and incorporate open-source expression and cancer survival data meta-analyses. We provide strong evidence for TAAR1 expression in the immune system and cancers revealed through NCBI GEO datamining and discuss its regulation in a spectrum of immune cell types as well as in numerous cancers. We discuss connections and logical directions for further study of TAAR1 in immunological function, and its potential role as a mediator or modulator of immune dysregulation, immunological effects of psychostimulant drugs of abuse, and cancer progression.",2018 Jun 26,"['Fleischer, Lisa M.', 'Somaiya, Rachana D.', 'Miller, Gregory M.']",Front Pharmacol,,,True
10fdb704d4a303ec84ac21438e38c93a798f2c34,PMC,"Comparative studies of alignment, alignment-free and SVM based approaches for predicting the hosts of viruses based on viral sequences",http://dx.doi.org/10.1038/s41598-018-28308-x,PMC6030160,29968780,CC BY,"Predicting the hosts of newly discovered viruses is important for pandemic surveillance of infectious diseases. We investigated the use of alignment-based and alignment-free methods and support vector machine using mononucleotide frequency and dinucleotide bias to predict the hosts of viruses, and applied these approaches to three datasets: rabies virus, coronavirus, and influenza A virus. For coronavirus, we used the spike gene sequences, while for rabies and influenza A viruses, we used the more conserved nucleoprotein gene sequences. We compared the three methods under different scenarios and showed that their performances are highly correlated with the variability of sequences and sample size. For conserved genes like the nucleoprotein gene, longer k-mers than mono- and dinucleotides are needed to better distinguish the sequences. We also showed that both alignment-based and alignment-free methods can accurately predict the hosts of viruses. When alignment is difficult to achieve or highly time-consuming, alignment-free methods can be a promising substitute to predict the hosts of new viruses.",2018 Jul 3,"['Li, Han', 'Sun, Fengzhu']",Sci Rep,,,False
9df4e2297f45f9a30993d6c526bb9bc87afa9ca4,PMC,"Comparative studies of alignment, alignment-free and SVM based approaches for predicting the hosts of viruses based on viral sequences",http://dx.doi.org/10.1038/s41598-018-28308-x,PMC6030160,29968780,CC BY,"Predicting the hosts of newly discovered viruses is important for pandemic surveillance of infectious diseases. We investigated the use of alignment-based and alignment-free methods and support vector machine using mononucleotide frequency and dinucleotide bias to predict the hosts of viruses, and applied these approaches to three datasets: rabies virus, coronavirus, and influenza A virus. For coronavirus, we used the spike gene sequences, while for rabies and influenza A viruses, we used the more conserved nucleoprotein gene sequences. We compared the three methods under different scenarios and showed that their performances are highly correlated with the variability of sequences and sample size. For conserved genes like the nucleoprotein gene, longer k-mers than mono- and dinucleotides are needed to better distinguish the sequences. We also showed that both alignment-based and alignment-free methods can accurately predict the hosts of viruses. When alignment is difficult to achieve or highly time-consuming, alignment-free methods can be a promising substitute to predict the hosts of new viruses.",2018 Jul 3,"['Li, Han', 'Sun, Fengzhu']",Sci Rep,,,True
10905e5423cc57fa9bd97aba8a348a3866953874,PMC,Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines,http://dx.doi.org/10.3389/fimmu.2018.01484,PMC6030256,29997628,CC BY,"Vaccines represent the discovery of utmost importance for global health, due to both prophylactic action to prevent infections and therapeutic intervention in neoplastic diseases. Despite this, current vaccination strategies need to be refined to successfully generate robust protective antigen-specific memory immune responses. To address this issue, one possibility is to exploit the high efficiency of dendritic cells (DCs) as antigen-presenting cells for T cell priming. DCs functional plasticity allows shaping the outcome of immune responses to achieve the required type of immunity. Therefore, the choice of adjuvants to guide and sustain DCs maturation, the design of multifaceted vehicles, and the choice of surface molecules to specifically target DCs represent the key issues currently explored in both preclinical and clinical settings. Here, we review advances in DCs-based vaccination approaches, which exploit direct in vivo DCs targeting and activation options. We also discuss the recent findings for efficient antitumor DCs-based vaccinations and combination strategies to reduce the immune tolerance promoted by the tumor microenvironment.",2018 Jun 27,"['Gornati, Laura', 'Zanoni, Ivan', 'Granucci, Francesca']",Front Immunol,,,True
7f8715a818bfd325bf4413d3c07003d7ce7b6f7e,PMC,Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation,http://dx.doi.org/10.1128/mBio.00898-18,PMC6030562,29970463,CC BY,"Human parainfluenza viruses cause a large burden of human respiratory illness. While much research relies upon viruses grown in cultured immortalized cells, human parainfluenza virus 3 (HPIV-3) evolves in culture. Cultured viruses differ in their properties compared to clinical strains. We present a genome-wide survey of HPIV-3 adaptations to culture using metagenomic next-generation sequencing of matched pairs of clinical samples and primary culture isolates (zero passage virus). Nonsynonymous changes arose during primary viral isolation, almost entirely in the genes encoding the two surface glycoproteins—the receptor binding protein hemagglutinin-neuraminidase (HN) or the fusion protein (F). We recovered genomes from 95 HPIV-3 primary culture isolates and 23 HPIV-3 strains directly from clinical samples. HN mutations arising during primary viral isolation resulted in substitutions at HN’s dimerization/F-interaction site, a site critical for activation of viral fusion. Alterations in HN dimer interface residues known to favor infection in culture occurred within 4 days (H552 and N556). A novel cluster of residues at a different face of the HN dimer interface emerged (P241 and R242) and imply a role in HPIV-3-mediated fusion. Functional characterization of these culture-associated HN mutations in a clinical isolate background revealed acquisition of the fusogenic phenotype associated with cultured HPIV-3; the HN-F complex showed enhanced fusion and decreased receptor-cleaving activity. These results utilize a method for identifying genome-wide changes associated with brief adaptation to culture to highlight the notion that even brief exposure to immortalized cells may affect key viral properties and underscore the balance of features of the HN-F complex required for fitness by circulating viruses.",2018 Jul 3,"['Iketani, Sho', 'Shean, Ryan C.', 'Ferren, Marion', 'Makhsous, Negar', 'Aquino, Dolly B.', 'des Georges, Amedee', 'Rima, Bert', 'Mathieu, Cyrille', 'Porotto, Matteo', 'Moscona, Anne', 'Greninger, Alexander L.']",mBio,,,True
04804494427631e79fc2a241c74adf6f607585f2,PMC,Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation,http://dx.doi.org/10.1128/mBio.00898-18,PMC6030562,29970463,CC BY,"Human parainfluenza viruses cause a large burden of human respiratory illness. While much research relies upon viruses grown in cultured immortalized cells, human parainfluenza virus 3 (HPIV-3) evolves in culture. Cultured viruses differ in their properties compared to clinical strains. We present a genome-wide survey of HPIV-3 adaptations to culture using metagenomic next-generation sequencing of matched pairs of clinical samples and primary culture isolates (zero passage virus). Nonsynonymous changes arose during primary viral isolation, almost entirely in the genes encoding the two surface glycoproteins—the receptor binding protein hemagglutinin-neuraminidase (HN) or the fusion protein (F). We recovered genomes from 95 HPIV-3 primary culture isolates and 23 HPIV-3 strains directly from clinical samples. HN mutations arising during primary viral isolation resulted in substitutions at HN’s dimerization/F-interaction site, a site critical for activation of viral fusion. Alterations in HN dimer interface residues known to favor infection in culture occurred within 4 days (H552 and N556). A novel cluster of residues at a different face of the HN dimer interface emerged (P241 and R242) and imply a role in HPIV-3-mediated fusion. Functional characterization of these culture-associated HN mutations in a clinical isolate background revealed acquisition of the fusogenic phenotype associated with cultured HPIV-3; the HN-F complex showed enhanced fusion and decreased receptor-cleaving activity. These results utilize a method for identifying genome-wide changes associated with brief adaptation to culture to highlight the notion that even brief exposure to immortalized cells may affect key viral properties and underscore the balance of features of the HN-F complex required for fitness by circulating viruses.",2018 Jul 3,"['Iketani, Sho', 'Shean, Ryan C.', 'Ferren, Marion', 'Makhsous, Negar', 'Aquino, Dolly B.', 'des Georges, Amedee', 'Rima, Bert', 'Mathieu, Cyrille', 'Porotto, Matteo', 'Moscona, Anne', 'Greninger, Alexander L.']",mBio,,,False
ad147a4279222c5e480a5636fb879540eded760e,PMC,Estimating the distance to an epidemic threshold,http://dx.doi.org/10.1098/rsif.2018.0034,PMC6030631,29950512,CC BY,"The epidemic threshold of the susceptible–infected–recovered model is a boundary separating parameters that permit epidemics from those that do not. This threshold corresponds to parameters where the system's equilibrium becomes unstable. Consequently, we use the average rate at which deviations from the equilibrium shrink to define a distance to this threshold. However, the vital dynamics of the host population may occur slowly even when transmission is far from threshold levels. Here, we show analytically how such slow dynamics can prevent estimation of the distance to the threshold from fluctuations in the susceptible population. Although these results are exact only in the limit of long-term observation of a large system, simulations show that they still provide useful insight into systems with a range of population sizes, environmental noise and observation schemes. Having established some guidelines about when estimates are accurate, we then illustrate how multiple distance estimates can be used to estimate the rate of approach to the threshold. The estimation approach is general and may be applicable to zoonotic pathogens such as Middle East respiratory syndrome-related coronavirus (MERS-CoV) as well as vaccine-preventable diseases like measles.",2018 Jun 27,"[""O'Dea, Eamon B."", 'Park, Andrew W.', 'Drake, John M.']",J R Soc Interface,,,True
8b30547cc365344758ee0e97c23d673d40302cb2,PMC,Estimating the distance to an epidemic threshold,http://dx.doi.org/10.1098/rsif.2018.0034,PMC6030631,29950512,CC BY,"The epidemic threshold of the susceptible–infected–recovered model is a boundary separating parameters that permit epidemics from those that do not. This threshold corresponds to parameters where the system's equilibrium becomes unstable. Consequently, we use the average rate at which deviations from the equilibrium shrink to define a distance to this threshold. However, the vital dynamics of the host population may occur slowly even when transmission is far from threshold levels. Here, we show analytically how such slow dynamics can prevent estimation of the distance to the threshold from fluctuations in the susceptible population. Although these results are exact only in the limit of long-term observation of a large system, simulations show that they still provide useful insight into systems with a range of population sizes, environmental noise and observation schemes. Having established some guidelines about when estimates are accurate, we then illustrate how multiple distance estimates can be used to estimate the rate of approach to the threshold. The estimation approach is general and may be applicable to zoonotic pathogens such as Middle East respiratory syndrome-related coronavirus (MERS-CoV) as well as vaccine-preventable diseases like measles.",2018 Jun 27,"[""O'Dea, Eamon B."", 'Park, Andrew W.', 'Drake, John M.']",J R Soc Interface,,,True
6ccce7b6fb9a213959f56ae465bb75ad130d6c9a,PMC,Accuracy of MRI diagnosis of early osteonecrosis of the femoral head: a meta-analysis and systematic review,http://dx.doi.org/10.1186/s13018-018-0836-8,PMC6031173,29973239,CC BY,"OBJECTIVE: To evaluate the overall diagnostic value related to magnetic resonance imaging (MRI) in patients with early osteonecrosis of the femoral head. METHODS: By searching multiple databases and sources, including PubMed, Cochrane, and Embase database, by the index words updated in December 2017, qualified studies were identified and relevant literature sources were also searched. The qualified studies included prospective cohort studies and cross-sectional studies. Heterogeneity of the included studies were reviewed to select proper effect model for pooled weighted sensitivity, specificity, and diagnostic odds ratio (DOR). Summary receiver operating characteristic (SROC) analyses were performed for meniscal tears. RESULTS: Forty-three studies related to diagnostic accuracy of MRI to detect early osteonecrosis of the femoral head were involved in the meta-analysis. The global sensitivity and specificity of MRI in early osteonecrosis of the femoral head were 93.0% (95% CI 92.0–94.0%) and 91.0% (95% CI 89.0%–93.0%), respectively. The global positive likelihood ratio and global negative likelihood ratio of MRI in early osteonecrosis of the femoral head were 2.74 (95% CI 1.98–3.79) and 0.18 (95% CI 0.14–0.23), respectively. The global DOR was 27.27 (95% CI 17.02–43.67), and the area under the SROC was 93.38% (95% CI 90.87%–95.89%). CONCLUSIONS: This review provides a systematic review and meta-analysis to evaluate the diagnostic accuracy of MRI in early osteonecrosis of the femoral head. Moderate to strong evidence indicated that MRI appears to be significantly associated with higher diagnostic accuracy for early osteonecrosis of the femoral head.",2018 Jul 4,"['Zhang, Ya-Zhou', 'Cao, Xu-Yang', 'Li, Xi-Cheng', 'Chen, Jia', 'Zhao, Yue-Yuan', 'Tian, Zhi', 'Zheng, Wang']",J Orthop Surg Res,,,True
334b38e4803085738b38d29775edea658bfb309b,PMC,Nanoparticles for Signaling in Biodiagnosis and Treatment of Infectious Diseases,http://dx.doi.org/10.3390/ijms19061627,PMC6032068,29857492,CC BY,"Advances in nanoparticle-based systems constitute a promising research area with important implications for the treatment of bacterial infections, especially against multidrug resistant strains and bacterial biofilms. Nanosystems may be useful for the diagnosis and treatment of viral and fungal infections. Commercial diagnostic tests based on nanosystems are currently available. Different methodologies based on nanoparticles (NPs) have been developed to detect specific agents or to distinguish between Gram-positive and Gram-negative microorganisms. Also, biosensors based on nanoparticles have been applied in viral detection to improve available analytical techniques. Several point-of-care (POC) assays have been proposed that can offer results faster, easier and at lower cost than conventional techniques and can even be used in remote regions for viral diagnosis. Nanoparticles functionalized with specific molecules may modulate pharmacokinetic targeting recognition and increase anti-infective efficacy. Quorum sensing is a stimuli-response chemical communication process correlated with population density that bacteria use to regulate biofilm formation. Disabling it is an emerging approach for combating its pathogenicity. Natural or synthetic inhibitors may act as antibiofilm agents and be useful for treating multi-drug resistant bacteria. Nanostructured materials that interfere with signal molecules involved in biofilm growth have been developed for the control of infections associated with biofilm-associated infections.",2018 May 31,"['Colino, Clara I.', 'Millán, Carmen Gutiérrez', 'Lanao, José M.']",Int J Mol Sci,,,True
80f244134084f44bfc86bbe102f338d18e219dbc,PMC,Bioactivities of Phenolics by Focusing on Suppression of Chronic Diseases: A Review,http://dx.doi.org/10.3390/ijms19061573,PMC6032343,29799460,CC BY,"Phenolics, which are secondary metabolites of plants, exhibit remarkable bioactivities. In this contribution, we have focused on their protective effect against chronic diseases rather than their antioxidant activities, which have been widely discussed in the literature. A large body of epidemiological studies has proven the bioactivities of phenolics in both standard compounds and natural extracts: namely, anticancer, anti-inflammatory, and antibacterial activities as well as reducing diabetes, cardiovascular disease, and neurodegenerative disease. Phenolics also display anti-analgesic, anti-allergic, and anti-Alzheimer’s properties. Thus, this review provides crucial information for better understanding the bioactivities of phenolics in foods and fills a gap in the existing collective and overall knowledge in the field.",2018 May 25,"['Shahidi, Fereidoon', 'Yeo, JuDong']",Int J Mol Sci,,,True
804533d11a3f44908f514922d18f2a79826471c2,PMC,Combined Rosiglitazone and Forskolin Have Neuroprotective Effects in SD Rats after Spinal Cord Injury,http://dx.doi.org/10.1155/2018/3897478,PMC6032969,30034460,CC BY,"The peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist rosiglitazone inhibits NF-κB expression and endogenous neural stem cell differentiation into neurons and reduces the inflammatory cascade after spinal cord injury (SCI). The aim of this study was to explore the mechanisms underlying rosiglitazone-mediated neuroprotective effects and regulation of the balance between the inflammatory cascade and generation of endogenous spinal cord neurons by using a spinal cord-derived neural stem cell culture system as well as SD rat SCI model. Activation of PPAR-γ could promote neural stem cell proliferation and inhibit PKA expression and neuronal formation in vitro. In the SD rat SCI model, the rosiglitazone + forskolin group showed better locomotor recovery compared to the rosiglitazone and forskolin groups. MAP2 expression was higher in the rosiglitazone + forskolin group than in the rosiglitazone group, NF-κB expression was lower in the rosiglitazone + forskolin group than in the forskolin group, and NeuN expression was higher in the rosiglitazone + forskolin group than in the forskolin group. PPAR-γ activation likely inhibits NF-κB, thereby reducing the inflammatory cascade, and PKA activation likely promotes neuronal cell regeneration.",2018 Jun 21,"['Meng, Qing-qi', 'Lei, Wei', 'Chen, Hao', 'Feng, Zhen-cheng', 'Hu, Li-qiong', 'Zhang, Xing-liang', 'Li, Siming']",PPAR Res,,,True
6be52161b7c2d20ad15f376399586a3ab395206d,PMC,Suffering a Loss Is Good Fortune: Myth or Reality?,http://dx.doi.org/10.1002/bdm.2056,PMC6033005,30008514,CC BY,"We sometimes decide to take an offered option that results in apparent loss (e.g., unpaid overtime). Mainstream decision theory does not predict or explain this as a choice we want to make, whereas such a choice has long been described and highly regarded by the traditional Chinese dogma “吃亏是福” (suffering a loss is good fortune). To explore what makes the dogma work, we developed a celebrity anecdote‐based scale to measure “Chikui” (suffering a loss) likelihood and found that:(i) people with higher scores on the Chikui Likelihood Scale (CLS) were more likely to report higher scores on subjective well‐being and the Socioeconomic Index for the present and (ii) the current Socioeconomic Index could be positively predicted not only by current CLS scores but also by retrospective CLS scores recalled for the past, and the predictive effect was enhanced with increasing time intervals. Our findings suggest that “suffering a loss is good fortune” is not a myth but a certain reality. © 2017 The Authors Journal of Behavioral Decision Making Published by John Wiley & Sons Ltd.",2018 Jul 29,"['Zhao, Cui‐Xia', 'Shen, Si‐Chu', 'Rao, Li‐Lin', 'Zheng, Rui', 'Liu, Huan', 'Li, Shu']",J Behav Decis Mak,,,True
0c95f3083af8f4daf852527cc3d25b6b8af3a54c,PMC,Automated TruTip nucleic acid extraction and purification from raw sputum,http://dx.doi.org/10.1371/journal.pone.0199869,PMC6033430,29975759,CC BY,"Automated nucleic acid extraction from primary (raw) sputum continues to be a significant technical challenge for molecular diagnostics. In this work, we developed a prototype open-architecture, automated nucleic acid workstation that includes a mechanical homogenization and lysis function integrated with heating and TruTip purification; optimized an extraction protocol for raw sputum; and evaluated system performance on primary clinical specimens. Eight samples could be processed within 70 min. The system efficiently homogenized primary sputa and doubled nucleic acid recovery relative to an automated protocol that did not incorporate sample homogenization. Nucleic acid recovery was at least five times higher from raw sputum as compared to that of matched sediments regardless of smear or culture grade, and the automated workstation reproducibly recovered PCR-detectable DNA to at least 80 CFU mL(-1) raw sputum. M. tuberculosis DNA was recovered and detected from 122/123 (99.2%) and 124/124 (100%) primary sputum and sediment extracts, respectively. There was no detectable cross-contamination across 53 automated system runs and amplification or fluorescent inhibitors (if present) were not detectable. The open fluidic architecture of the prototype automated workstation yields purified sputum DNA that can be used for any molecular diagnostic test. The ability to transfer TruTip protocols between personalized, on-demand pipetting tools and the fully automated workstation also affords public health agencies an opportunity to standardize sputum nucleic acid sample preparation procedures, reagents, and quality control across multiple levels of the health care system.",2018 Jul 5,"['Thakore, Nitu', 'Norville, Ryan', 'Franke, Molly', 'Calderon, Roger', 'Lecca, Leonid', 'Villanueva, Michael', 'Murray, Megan B.', 'Cooney, Christopher G.', 'Chandler, Darrell P.', 'Holmberg, Rebecca C.']",PLoS One,,,True
d06c36f9ef81b72f1bdad04a8fd4579d0016c2e9,PMC,Induced CNS expression of CXCL1 augments neurologic disease in a murine model of multiple sclerosis via enhanced neutrophil recruitment,http://dx.doi.org/10.1002/eji.201747442,PMC6033633,29697856,CC BY,"Increasing evidence points to an important role for neutrophils in participating in the pathogenesis of the human demyelinating disease MS and the animal model EAE. Therefore, a better understanding of the signals controlling migration of neutrophils as well as evaluating the role of these cells in demyelination is important to define cellular components that contribute to disease in MS patients. In this study, we examined the functional role of the chemokine CXCL1 in contributing to neuroinflammation and demyelination in EAE. Using transgenic mice in which expression of CXCL1 is under the control of a tetracycline‐inducible promoter active within glial fibrillary acidic protein‐positive cells, we have shown that sustained CXCL1 expression within the CNS increased the severity of clinical and histologic disease that was independent of an increase in the frequency of encephalitogenic Th1 and Th17 cells. Rather, disease was associated with enhanced recruitment of CD11b(+)Ly6G(+) neutrophils into the spinal cord. Targeting neutrophils resulted in a reduction in demyelination arguing for a role for these cells in myelin damage. Collectively, these findings emphasize that CXCL1‐mediated attraction of neutrophils into the CNS augments demyelination suggesting that this signaling pathway may offer new targets for therapeutic intervention.",2018 Jul 16,"['Grist, Jonathan J.', 'Marro, Brett S.', 'Skinner, Dominic D.', 'Syage, Amber R.', 'Worne, Colleen', 'Doty, Daniel J.', 'Fujinami, Robert S.', 'Lane, Thomas E.']",Eur J Immunol,,,True
5ce94f573760ca6a978bbfea639527a22529c24e,PMC,Induced CNS expression of CXCL1 augments neurologic disease in a murine model of multiple sclerosis via enhanced neutrophil recruitment,http://dx.doi.org/10.1002/eji.201747442,PMC6033633,29697856,CC BY,"Increasing evidence points to an important role for neutrophils in participating in the pathogenesis of the human demyelinating disease MS and the animal model EAE. Therefore, a better understanding of the signals controlling migration of neutrophils as well as evaluating the role of these cells in demyelination is important to define cellular components that contribute to disease in MS patients. In this study, we examined the functional role of the chemokine CXCL1 in contributing to neuroinflammation and demyelination in EAE. Using transgenic mice in which expression of CXCL1 is under the control of a tetracycline‐inducible promoter active within glial fibrillary acidic protein‐positive cells, we have shown that sustained CXCL1 expression within the CNS increased the severity of clinical and histologic disease that was independent of an increase in the frequency of encephalitogenic Th1 and Th17 cells. Rather, disease was associated with enhanced recruitment of CD11b(+)Ly6G(+) neutrophils into the spinal cord. Targeting neutrophils resulted in a reduction in demyelination arguing for a role for these cells in myelin damage. Collectively, these findings emphasize that CXCL1‐mediated attraction of neutrophils into the CNS augments demyelination suggesting that this signaling pathway may offer new targets for therapeutic intervention.",2018 Jul 16,"['Grist, Jonathan J.', 'Marro, Brett S.', 'Skinner, Dominic D.', 'Syage, Amber R.', 'Worne, Colleen', 'Doty, Daniel J.', 'Fujinami, Robert S.', 'Lane, Thomas E.']",Eur J Immunol,,,False
3344848f97c5d7b1a4f07d6be4e6068819f5166b,PMC,Induced CNS expression of CXCL1 augments neurologic disease in a murine model of multiple sclerosis via enhanced neutrophil recruitment,http://dx.doi.org/10.1002/eji.201747442,PMC6033633,29697856,CC BY,"Increasing evidence points to an important role for neutrophils in participating in the pathogenesis of the human demyelinating disease MS and the animal model EAE. Therefore, a better understanding of the signals controlling migration of neutrophils as well as evaluating the role of these cells in demyelination is important to define cellular components that contribute to disease in MS patients. In this study, we examined the functional role of the chemokine CXCL1 in contributing to neuroinflammation and demyelination in EAE. Using transgenic mice in which expression of CXCL1 is under the control of a tetracycline‐inducible promoter active within glial fibrillary acidic protein‐positive cells, we have shown that sustained CXCL1 expression within the CNS increased the severity of clinical and histologic disease that was independent of an increase in the frequency of encephalitogenic Th1 and Th17 cells. Rather, disease was associated with enhanced recruitment of CD11b(+)Ly6G(+) neutrophils into the spinal cord. Targeting neutrophils resulted in a reduction in demyelination arguing for a role for these cells in myelin damage. Collectively, these findings emphasize that CXCL1‐mediated attraction of neutrophils into the CNS augments demyelination suggesting that this signaling pathway may offer new targets for therapeutic intervention.",2018 Jul 16,"['Grist, Jonathan J.', 'Marro, Brett S.', 'Skinner, Dominic D.', 'Syage, Amber R.', 'Worne, Colleen', 'Doty, Daniel J.', 'Fujinami, Robert S.', 'Lane, Thomas E.']",Eur J Immunol,,,False
15ba6bd83b77850bcc2a925dbe99fa6bcc5fa51d,PMC,Preparedness and response against diseases with epidemic potential in the European Union: a qualitative case study of Middle East Respiratory Syndrome (MERS) and poliomyelitis in five member states,http://dx.doi.org/10.1186/s12913-018-3326-0,PMC6034236,29976185,CC BY,"BACKGROUND: EU Decision 1082/2013/EU on serious cross-border health threats provides a legal basis for collaboration between EU Member States, and between international and European level institutions on preparedness, prevention, and mitigation in the event of a public health emergency. The Decision provides a context for the present study, which aims to identify good practices and lessons learned in preparedness and response to Middle East Respiratory Syndrome (MERS) (in UK, Greece, and Spain) and poliomyelitis (in Poland and Cyprus). METHODS: Based on a documentary review, followed by five week-long country visits involving a total of 61 interviews and group discussions with experts from both the health and non-health sectors, this qualitative case study has investigated six issues related to preparedness and response to MERS and poliomyelitis: national plans and overall preparedness capacity; training and exercises; risk communication; linking policy and implementation; interoperability between the health and non-health sectors; and cross-border collaboration. RESULTS: Preparedness and response plans for MERS and poliomyelitis were in place in the participating countries, with a high level of technical expertise available to implement them. Nevertheless, formal evaluation of the responses to previous public health emergencies have sometimes been limited, so lessons learned may not be reflected in updated plans, thereby risking mistakes being repeated in future. The nature and extent of inter-sectoral collaboration varied according to the sectors involved, with those sectors that have traditionally had good collaboration (e.g. animal health and food safety), as well as those that have a financial incentive for controlling infectious diseases (e.g. agriculture, tourism, and air travel) seen as most likely to have integrated public health preparedness and response plans. Although the formal protocols for inter-sectoral collaboration were not always up to date, good personal relations were reported within the relevant professional networks, which could be brought into play in the event of a public health emergency. Cross-border collaboration was greatly facilitated if the neighbouring country was a fellow EU Member State. CONCLUSIONS: Infectious disease outbreaks remain as an ongoing threat. Efforts are required to ensure that core public health capacities for the full range of preparedness and response activities are sustained. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12913-018-3326-0) contains supplementary material, which is available to authorized users.",2018 Jul 6,"['Kinsman, John', 'Angrén, John', 'Elgh, Fredrik', 'Furberg, Maria', 'Mosquera, Paola A.', 'Otero-García, Laura', 'Snacken, René', 'Derrough, Tarik', 'Carrillo Santisteve, Paloma', 'Ciotti, Massimo', 'Tsolova, Svetla']",BMC Health Serv Res,,,False
012debf5a240a496518af146ddfc16c958339c2b,PMC,Preparedness and response against diseases with epidemic potential in the European Union: a qualitative case study of Middle East Respiratory Syndrome (MERS) and poliomyelitis in five member states,http://dx.doi.org/10.1186/s12913-018-3326-0,PMC6034236,29976185,CC BY,"BACKGROUND: EU Decision 1082/2013/EU on serious cross-border health threats provides a legal basis for collaboration between EU Member States, and between international and European level institutions on preparedness, prevention, and mitigation in the event of a public health emergency. The Decision provides a context for the present study, which aims to identify good practices and lessons learned in preparedness and response to Middle East Respiratory Syndrome (MERS) (in UK, Greece, and Spain) and poliomyelitis (in Poland and Cyprus). METHODS: Based on a documentary review, followed by five week-long country visits involving a total of 61 interviews and group discussions with experts from both the health and non-health sectors, this qualitative case study has investigated six issues related to preparedness and response to MERS and poliomyelitis: national plans and overall preparedness capacity; training and exercises; risk communication; linking policy and implementation; interoperability between the health and non-health sectors; and cross-border collaboration. RESULTS: Preparedness and response plans for MERS and poliomyelitis were in place in the participating countries, with a high level of technical expertise available to implement them. Nevertheless, formal evaluation of the responses to previous public health emergencies have sometimes been limited, so lessons learned may not be reflected in updated plans, thereby risking mistakes being repeated in future. The nature and extent of inter-sectoral collaboration varied according to the sectors involved, with those sectors that have traditionally had good collaboration (e.g. animal health and food safety), as well as those that have a financial incentive for controlling infectious diseases (e.g. agriculture, tourism, and air travel) seen as most likely to have integrated public health preparedness and response plans. Although the formal protocols for inter-sectoral collaboration were not always up to date, good personal relations were reported within the relevant professional networks, which could be brought into play in the event of a public health emergency. Cross-border collaboration was greatly facilitated if the neighbouring country was a fellow EU Member State. CONCLUSIONS: Infectious disease outbreaks remain as an ongoing threat. Efforts are required to ensure that core public health capacities for the full range of preparedness and response activities are sustained. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12913-018-3326-0) contains supplementary material, which is available to authorized users.",2018 Jul 6,"['Kinsman, John', 'Angrén, John', 'Elgh, Fredrik', 'Furberg, Maria', 'Mosquera, Paola A.', 'Otero-García, Laura', 'Snacken, René', 'Derrough, Tarik', 'Carrillo Santisteve, Paloma', 'Ciotti, Massimo', 'Tsolova, Svetla']",BMC Health Serv Res,,,True
87e2c4caa0401de97f31022abe3d31b9313978e9,PMC,"Epidemiology and clinical characteristics of acute respiratory tract infections among hospitalized infants and young children in Chengdu, West China, 2009–2014",http://dx.doi.org/10.1186/s12887-018-1203-y,PMC6034247,29976175,CC BY,"BACKGROUND: Acute respiratory infection (ARI) is the leading cause of morbidity and mortality in pediatric patients worldwide and imposes an intense pressure on health care facilities. Data on the epidemiology profiles of ARIs are scarce in the western and rural areas of China. The purpose of the current study is to provide data on the presence of potential pathogens of ARIs in hospitalized children in Chengdu, west China. METHODS: Respiratory specimens were obtained from hospitalized patients (under 6 years old) with ARIs in a local hospital in Chengdu. Eight respiratory viruses were identified by PCR and 6 respiratory bacteria by biochemical reactions and Analytical Profile Index (API). Pathogens profiles, clinical characteristics and seasonality were analyzed. RESULTS: Fifty-one percent of patients were identified with at least one respiratory pathogen. Human rhinovirus (HRV) (23%), Respiratory syncytial virus (RSV) (22.7%) was the most commonly identified viruses, with Klebsiella pneumoniae (11.5%) the most commonly identified bacterium in the study. The presences of more than one pathogen were found, and multiple viral, bacterial, viral/bacterial combinations were identified in 14.9, 3.3 and 13.9% of patients respectively. Respiratory viruses were identified throughout the year with a seasonal peak in December–February. Pathogens profiles and clinical associations were different between infants (< 1 year of age) and older children (> 1 year of age). Infants with ARIs were more likely to have one or more viruses than older children. Infants identified with multiple pathogens had significantly higher proportions of tachypnea than infants that were not. CONCLUSIONS: This study demonstrated that viral agents were frequently found in hospitalized children with ARI in Chengdu during the study period. This study gives us better information on the pathogen profiles, clinical associations, co-infection combinations and seasonal features of ARIs in hospitalized children, which is important for diagnoses and treatment of ARIs, as well as implementation of vaccines in this area. Moreover, future efforts in reducing the impact of ARIs will depend on programs in which available vaccines, especially vaccines on RSV, HRV and S. pneumoniae could be employed in this region and new vaccines could be developed against common pathogens.",2018 Jul 5,"['Chen, Jiayi', 'Hu, Pengwei', 'Zhou, Tao', 'Zheng, Tianli', 'Zhou, Lingxu', 'Jiang, Chunping', 'Pei, Xiaofang']",BMC Pediatr,,,True
7df2110a81cac12da76c7d4c72a53f58f4505c8b,PMC,Controlled efficacy trial confirming toltrazuril resistance in a field isolate of ovine Eimeria spp.,http://dx.doi.org/10.1186/s13071-018-2976-4,PMC6034276,29976240,CC BY,"BACKGROUND: Coccidiosis due to Eimeria spp. infections in lambs causes increased mortality and substantial production losses, and anticoccidials are important for control of the infection. Anticoccidial resistance has been reported in poultry and swine, and we recently described reduced toltrazuril efficacy in ovine Eimeria spp. in some Norwegian sheep farms using a newly developed faecal oocyst count reduction test (FOCRT). The aim of the present study was to use a controlled efficacy trial to assess the efficacy of toltrazuril against a field isolate suspected of being resistant. METHODS: Twenty lambs, 17–22 days old and raised protected against exposure to coccidia, were infected with a field isolate of 100,000 Eimeria spp. oocysts. This isolate was obtained from a farm with a previously calculated drug efficacy of 56% (95% confidence interval: -433.9 to 96.6%). At day 7 post-infection, 10 of the lambs were orally treated with 20 mg/kg toltrazuril (Baycox Sheep vet., Bayer Animal Health), while the other 10 lambs (controls) were given physiological saline. Clinical examinations were conducted, and weight gains recorded. Daily faecal samples were scored for diarrhoea on a scale from 1 to 5, and oocyst excretion was determined using a modified McMaster technique. Oocysts were morphologically identified to species level. At 17–24 days post-infection, the lambs were euthanized and necropsied. RESULTS: The tested Eimeria isolate was resistant against toltrazuril, and resistance was seen in both pathogenic and non-pathogenic species. In addition, no significant differences in faecal score, growth, gross pathology or histological changes were identified between the two groups. The pathogenic E. ovinoidalis was the dominant species, and no significant difference in the individual prevalence of E. ovinoidalis post-treatment was found between treated (66.9%) and control lambs (61.9%). Other species identified included E. crandallis/weybridgensis, E. parva, E. marsica, E. faurei, E. pallida, E. ahsata and E. bakuensis. CONCLUSIONS: This study confirms toltrazuril resistance in ovine Eimeria spp.; in addition, the data support the use of FOCRT as an appropriate tool for field evaluation of anticoccidial efficacy. Due to limited anticoccidial treatment alternatives, these findings may have important implications for the sheep industry, particularly in northern Europe. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-018-2976-4) contains supplementary material, which is available to authorized users.",2018 Jul 5,"['Odden, Ane', 'Enemark, Heidi L.', 'Ruiz, Antonio', 'Robertson, Lucy J.', 'Ersdal, Cecilie', 'Nes, Silje K.', 'Tømmerberg, Vibeke', 'Stuen, Snorre']",Parasit Vectors,,,False
0e418b5180b799b8e0bfdbf79e977e2727c353b3,PMC,Controlled efficacy trial confirming toltrazuril resistance in a field isolate of ovine Eimeria spp.,http://dx.doi.org/10.1186/s13071-018-2976-4,PMC6034276,29976240,CC BY,"BACKGROUND: Coccidiosis due to Eimeria spp. infections in lambs causes increased mortality and substantial production losses, and anticoccidials are important for control of the infection. Anticoccidial resistance has been reported in poultry and swine, and we recently described reduced toltrazuril efficacy in ovine Eimeria spp. in some Norwegian sheep farms using a newly developed faecal oocyst count reduction test (FOCRT). The aim of the present study was to use a controlled efficacy trial to assess the efficacy of toltrazuril against a field isolate suspected of being resistant. METHODS: Twenty lambs, 17–22 days old and raised protected against exposure to coccidia, were infected with a field isolate of 100,000 Eimeria spp. oocysts. This isolate was obtained from a farm with a previously calculated drug efficacy of 56% (95% confidence interval: -433.9 to 96.6%). At day 7 post-infection, 10 of the lambs were orally treated with 20 mg/kg toltrazuril (Baycox Sheep vet., Bayer Animal Health), while the other 10 lambs (controls) were given physiological saline. Clinical examinations were conducted, and weight gains recorded. Daily faecal samples were scored for diarrhoea on a scale from 1 to 5, and oocyst excretion was determined using a modified McMaster technique. Oocysts were morphologically identified to species level. At 17–24 days post-infection, the lambs were euthanized and necropsied. RESULTS: The tested Eimeria isolate was resistant against toltrazuril, and resistance was seen in both pathogenic and non-pathogenic species. In addition, no significant differences in faecal score, growth, gross pathology or histological changes were identified between the two groups. The pathogenic E. ovinoidalis was the dominant species, and no significant difference in the individual prevalence of E. ovinoidalis post-treatment was found between treated (66.9%) and control lambs (61.9%). Other species identified included E. crandallis/weybridgensis, E. parva, E. marsica, E. faurei, E. pallida, E. ahsata and E. bakuensis. CONCLUSIONS: This study confirms toltrazuril resistance in ovine Eimeria spp.; in addition, the data support the use of FOCRT as an appropriate tool for field evaluation of anticoccidial efficacy. Due to limited anticoccidial treatment alternatives, these findings may have important implications for the sheep industry, particularly in northern Europe. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-018-2976-4) contains supplementary material, which is available to authorized users.",2018 Jul 5,"['Odden, Ane', 'Enemark, Heidi L.', 'Ruiz, Antonio', 'Robertson, Lucy J.', 'Ersdal, Cecilie', 'Nes, Silje K.', 'Tømmerberg, Vibeke', 'Stuen, Snorre']",Parasit Vectors,,,False
ef000d8cdab3895e2321286f16cce2b8aea458d1,PMC,Controlled efficacy trial confirming toltrazuril resistance in a field isolate of ovine Eimeria spp.,http://dx.doi.org/10.1186/s13071-018-2976-4,PMC6034276,29976240,CC BY,"BACKGROUND: Coccidiosis due to Eimeria spp. infections in lambs causes increased mortality and substantial production losses, and anticoccidials are important for control of the infection. Anticoccidial resistance has been reported in poultry and swine, and we recently described reduced toltrazuril efficacy in ovine Eimeria spp. in some Norwegian sheep farms using a newly developed faecal oocyst count reduction test (FOCRT). The aim of the present study was to use a controlled efficacy trial to assess the efficacy of toltrazuril against a field isolate suspected of being resistant. METHODS: Twenty lambs, 17–22 days old and raised protected against exposure to coccidia, were infected with a field isolate of 100,000 Eimeria spp. oocysts. This isolate was obtained from a farm with a previously calculated drug efficacy of 56% (95% confidence interval: -433.9 to 96.6%). At day 7 post-infection, 10 of the lambs were orally treated with 20 mg/kg toltrazuril (Baycox Sheep vet., Bayer Animal Health), while the other 10 lambs (controls) were given physiological saline. Clinical examinations were conducted, and weight gains recorded. Daily faecal samples were scored for diarrhoea on a scale from 1 to 5, and oocyst excretion was determined using a modified McMaster technique. Oocysts were morphologically identified to species level. At 17–24 days post-infection, the lambs were euthanized and necropsied. RESULTS: The tested Eimeria isolate was resistant against toltrazuril, and resistance was seen in both pathogenic and non-pathogenic species. In addition, no significant differences in faecal score, growth, gross pathology or histological changes were identified between the two groups. The pathogenic E. ovinoidalis was the dominant species, and no significant difference in the individual prevalence of E. ovinoidalis post-treatment was found between treated (66.9%) and control lambs (61.9%). Other species identified included E. crandallis/weybridgensis, E. parva, E. marsica, E. faurei, E. pallida, E. ahsata and E. bakuensis. CONCLUSIONS: This study confirms toltrazuril resistance in ovine Eimeria spp.; in addition, the data support the use of FOCRT as an appropriate tool for field evaluation of anticoccidial efficacy. Due to limited anticoccidial treatment alternatives, these findings may have important implications for the sheep industry, particularly in northern Europe. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-018-2976-4) contains supplementary material, which is available to authorized users.",2018 Jul 5,"['Odden, Ane', 'Enemark, Heidi L.', 'Ruiz, Antonio', 'Robertson, Lucy J.', 'Ersdal, Cecilie', 'Nes, Silje K.', 'Tømmerberg, Vibeke', 'Stuen, Snorre']",Parasit Vectors,,,True
64a2b883a0ce91110c5cd56722520d862476ba3e,PMC,Major medical causes by breed and life stage for dogs presented at veterinary clinics in the Republic of Korea: a survey of electronic medical records,http://dx.doi.org/10.7717/peerj.5161,PMC6035722,30013835,CC BY,"BACKGROUND: Age and breed are considered the greatest risk factors for disease prevalence and mortality in companion dogs. Understanding the prevalence of diseases, in relation to age and breed, would support appropriate guidance for future health care strategies and provide useful information for the early diagnosis of diseases. The purpose of this study was to investigate the major medical causes for dogs visiting primary-care veterinary clinics in the Republic of Korea, stratified by age and breed. METHODS: A total of 15,531 medical records of canine patients were analyzed from 11 veterinary clinics who shared data from January 1, 2016 to December 31, 2016. An electronic medical record (EMR) system was used for data collection, which included the animal identification number, age, breed, gender, neuter status, clinical information, and diagnosis. EMR data were classified using the International Classification of Disease system from the World Health Organization; presenting signs or diagnoses were identified according to breed and life stage. RESULTS: Within the age groups, preventive medicine (16.7% confidence intervals (CI) [15.9–17.5]) was the most common cause for clinic visits for the <1 year and 1–3 year groups. Additionally, neutering surgery (6.6% CI [6.0–7.1]) and patella luxation (1.4% CI [1.8–2.7]) were frequently performed in these age groups. In the 4–6 year group, otitis externa (8.8% CI [7.8–10.0]) and dermatitis or eczema (8.5% CI [7.5–9.6]) were common medical problems. In older dogs (>10 year), the prevalences of heart disease, kidney disease, Cushing’s disease, and mammary tumors were higher than in the other age groups. Small and toy breed dogs comprised 67.7% of all dogs in this analysis. For all breeds, otitis externa, dermatitis or eczema, vomiting, and diarrhea were common medical problems. DISCUSSION: This study identified the most common medical disorders and differences in prevalences of diseases, according to age and breeds. The information from EMRs for dogs visiting primary-care veterinary clinics can provide background knowledge that is required to enable a better understanding of disease patterns and occurrence by age and breeds. The information from this study could enable the creation of strategies for preventing diseases and enable the identification of health problems for more effective disease management in companion dogs.",2018 Jul 3,"['Kim, Eunju', 'Choe, Changyong', 'Yoo, Jae Gyu', 'Oh, Sang-Ik', 'Jung, Younghun', 'Cho, Ara', 'Kim, Suhee', 'Do, Yoon Jung']",PeerJ,,,True
de452bf070bb2c100cab63901495507c492e6ada,PMC,Differential Shape of Geminivirus Mutant Spectra Across Cultivated and Wild Hosts With Invariant Viral Consensus Sequences,http://dx.doi.org/10.3389/fpls.2018.00932,PMC6036239,30013589,CC BY,"Geminiviruses (family Geminiviridae) possess single-stranded circular DNA genomes that are replicated by cellular polymerases in plant host cell nuclei. In their hosts, geminivirus populations behave as ensembles of mutant and recombinant genomes, known as viral quasispecies. This favors the emergence of new geminiviruses with altered host range, facilitating new or more severe diseases or overcoming resistance traits. In warm and temperate areas several whitefly-transmitted geminiviruses of the genus Begomovirus cause the tomato yellow leaf curl disease (TYLCD) with significant economic consequences. TYLCD is frequently controlled in commercial tomatoes by using the dominant Ty-1 resistance gene. Over a 45 day period we have studied the diversification of three begomoviruses causing TYLCD: tomato yellow leaf curl virus (TYLCV), tomato yellow leaf curl Sardinia virus (TYLCSV) and tomato yellow leaf curl Malaga virus (TYLCMaV, a natural recombinant between TYLCV and TYLCSV). Viral quasispecies resulting from inoculation of geminivirus infectious clones were examined in plants of susceptible tomato (ty-1/ty-1), heterozygous resistant tomato (Ty-1/ty-1), common bean, and the wild reservoir Solanum nigrum. Differences in virus fitness across hosts were observed while viral consensus sequences remained invariant. However, the complexity and heterogeneity of the quasispecies were high, especially in common bean and the wild host. Interestingly, the presence or absence of the Ty-1 allele in tomato did not lead to differences in begomovirus mutant spectra. However, the fitness decrease of TYLCSV and TYLCV in tomato at 45 dpi might be related to an increase in CP (Coat protein) mutation frequency. In Solanum nigrum the recombinant TYLCMaV, which showed lower fitness than TYLCSV, at 45 dpi actively explored Rep (Replication associated protein) ORF but not the overlapping C4. Our results underline the importance of begomovirus mutant spectra during infections. This is especially relevant in the wild reservoir of the viruses, which has the potential to maintain highly diverse mutant spectra without modifying their consensus sequences.",2018 Jul 2,"['Sánchez-Campos, Sonia', 'Domínguez-Huerta, Guillermo', 'Díaz-Martínez, Luis', 'Tomás, Diego M.', 'Navas-Castillo, Jesús', 'Moriones, Enrique', 'Grande-Pérez, Ana']",Front Plant Sci,,,True
2f5ad2dee412dbb5a043d1a1c7aa2e0389bb2c7a,PMC,A Multiplex Asymmetric Reverse Transcription-PCR Assay Combined With an Electrochemical DNA Sensor for Simultaneously Detecting and Subtyping Influenza A Viruses,http://dx.doi.org/10.3389/fmicb.2018.01405,PMC6036258,30013525,CC BY,"The reliable and rapid detection of viral pathogens that cause respiratory infections provide physicians several advantages in treating patients and managing outbreaks. The Luminex respiratory virus panel (RVP) assay has been shown to be comparable to or superior to culture/direct fluorescent-antibody assays (DFAs) and nucleic acid tests that are used to diagnose respiratory viral infections. We developed a multiplex asymmetric reverse transcription (RT)-PCR assay that can simultaneously differentiate all influenza A virus epidemic subtypes. The amplified products were hybridized with an electrochemical DNA sensor, and the results were automatically acquired. The limits of detection (LoDs) of both the Luminex RVP assay and the multiplex RT-PCR-electrochemical DNA sensor were 10(1) TCID(50) for H1N1 virus and 10(2) TCID(50) for H3N2 virus. The specificity assessment of the multiplex RT-PCR-electrochemical DNA sensor showed no cross-reactivity among different influenza A subtypes or with other non-influenza respiratory viruses. In total, 3098 respiratory tract specimens collected from padiatric patients diagnosed with pneumonia were tested. More than half (43, 53.75%) of the specimens positive for influenza A viruses could not be further subtyped using the Luminex RVP assay. Among the remaining 15 specimens that were not subtyped, not degraded, and in sufficient amounts for the multiplex RT-PCR-electrochemical DNA sensor test, all (100%) were H3N2 positive. Therefore, the sensitivity of the Luminex RVP assay for influenza A virus was 46.25%, whereas the sensitivity of the multiplex RT-PCR-electrochemical DNA sensor for the clinical H1N1 and H3N2 specimens was 100%. The sensitivities of the multiplex RT-PCR-electrochemical DNA sensor for the avian H5N1, H5N6, H9N2, and H10N8 viruses were 100%, whereas that for H7N9 virus was 85.19%. We conclude that the multiplex RT-PCR-electrochemical DNA sensor is a reliable method for the rapid and accurate detection of highly variable influenza A viruses in respiratory infections with greater detection sensitivity than that of the Luminex xTAG assay. The high mutation rate of influenza A viruses, particularly H3N2 during the 2014 to 2016 epidemic seasons, has a strong impact on diagnosis. A study involving more positive specimens from all influenza A virus epidemic subtypes is required to fully assess the performance of the assay.",2018 Jun 27,"['Xu, Lili', 'Jiang, Xiwen', 'Zhu, Yun', 'Duan, Yali', 'Huang, Taosheng', 'Huang, Zhiwen', 'Liu, Chunyan', 'Xu, Baoping', 'Xie, Zhengde']",Front Microbiol,,,True
621832d547930a8c23859fa443c2c9c38ff07e42,PMC,Expression Profiles of mRNA and lncRNA in HCT-8 Cells Infected With Cryptosporidium parvum IId Subtype,http://dx.doi.org/10.3389/fmicb.2018.01409,PMC6036261,30013528,CC BY,"Cryptosporidium parvum is one of the most important enteric protozoan pathogens, responsible for severe diarrhea in immunocompromised human and livestock. However, few effective agents were available for controlling this parasite. Accumulating evidences suggest that long non-coding RNA (lncRNA) played key roles in many diseases through regulating the gene expression. Here, the expression profiles of lncRNAs and mRNAs were analyzed in HCT-8 cells infected with C. parvum IId subtype using microarray assay. A total of 821 lncRNAs and 1,349 mRNAs were differentially expressed in infected cells at 24 h post infection (pi). Of them, all five types of lncRNAs were identified, including 22 sense, 280 antisense, 312 intergenic, 44 divergent, 33 intronic lncRNAs, and 130 lncRNAs that were not found the relationship with mRNAs’ location. Additionally, real-time polymerase chain reactions of 10 lncRNAs and 10 mRNAs randomly selected were successfully confirmed the microarray results. The co-expression and target prediction analysis indicated that 27 mRNAs were cis-regulated by 29 lncRNAs and 109 were trans-regulated by 114 lncRNAs. These predicted targets were enriched in several pathways involved in the interaction between host and C. parvum, e.g., hedgehog signaling pathway, Wnt signaling pathway, and tight junction, suggesting that these differentially expressed lncRNAs would play important regulating roles during the infection of C. parvum IId subtype.",2018 Jun 27,"['Liu, Ting-Li', 'Fan, Xian-Chen', 'Li, Yun-Hui', 'Yuan, Ya-Jie', 'Yin, Yan-Ling', 'Wang, Xue-Ting', 'Zhang, Long-Xian', 'Zhao, Guang-Hui']",Front Microbiol,,,True
2b420869104820f327acb9db991fb1fe7ec281b4,PMC,Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya,http://dx.doi.org/10.1093/infdis/jiy098,PMC6037089,29741740,CC BY,"BACKGROUND: Human coronavirus NL63 (HCoV-NL63) is a globally endemic pathogen causing mild and severe respiratory tract infections with reinfections occurring repeatedly throughout a lifetime. METHODS: Nasal samples were collected in coastal Kenya through community-based and hospital-based surveillance. HCoV-NL63 was detected with multiplex real-time reverse transcription PCR, and positive samples were targeted for nucleotide sequencing of the spike (S) protein. Additionally, paired samples from 25 individuals with evidence of repeat HCoV-NL63 infection were selected for whole-genome virus sequencing. RESULTS: HCoV-NL63 was detected in 1.3% (75/5573) of child pneumonia admissions. Two HCoV-NL63 genotypes circulated in Kilifi between 2008 and 2014. Full genome sequences formed a monophyletic clade closely related to contemporary HCoV-NL63 from other global locations. An unexpected pattern of repeat infections was observed with some individuals showing higher viral titers during their second infection. Similar patterns for 2 other endemic coronaviruses, HCoV-229E and HCoV-OC43, were observed. Repeat infections by HCoV-NL63 were not accompanied by detectable genotype switching. CONCLUSIONS: In this coastal Kenya setting, HCoV-NL63 exhibited low prevalence in hospital pediatric pneumonia admissions. Clade persistence with low genetic diversity suggest limited immune selection, and absence of detectable clade switching in reinfections indicates initial exposure was insufficient to elicit a protective immune response.",2018 Jun 1,"['Kiyuka, Patience K', 'Agoti, Charles N', 'Munywoki, Patrick K', 'Njeru, Regina', 'Bett, Anne', 'Otieno, James R', 'Otieno, Grieven P', 'Kamau, Everlyn', 'Clark, Taane G', 'van der Hoek, Lia', 'Kellam, Paul', 'Nokes, D James', 'Cotten, Matthew']",J Infect Dis,,,True
7d81a14cd9a930300f375d8ab3c25efc418af46b,PMC,Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya,http://dx.doi.org/10.1093/infdis/jiy098,PMC6037089,29741740,CC BY,"BACKGROUND: Human coronavirus NL63 (HCoV-NL63) is a globally endemic pathogen causing mild and severe respiratory tract infections with reinfections occurring repeatedly throughout a lifetime. METHODS: Nasal samples were collected in coastal Kenya through community-based and hospital-based surveillance. HCoV-NL63 was detected with multiplex real-time reverse transcription PCR, and positive samples were targeted for nucleotide sequencing of the spike (S) protein. Additionally, paired samples from 25 individuals with evidence of repeat HCoV-NL63 infection were selected for whole-genome virus sequencing. RESULTS: HCoV-NL63 was detected in 1.3% (75/5573) of child pneumonia admissions. Two HCoV-NL63 genotypes circulated in Kilifi between 2008 and 2014. Full genome sequences formed a monophyletic clade closely related to contemporary HCoV-NL63 from other global locations. An unexpected pattern of repeat infections was observed with some individuals showing higher viral titers during their second infection. Similar patterns for 2 other endemic coronaviruses, HCoV-229E and HCoV-OC43, were observed. Repeat infections by HCoV-NL63 were not accompanied by detectable genotype switching. CONCLUSIONS: In this coastal Kenya setting, HCoV-NL63 exhibited low prevalence in hospital pediatric pneumonia admissions. Clade persistence with low genetic diversity suggest limited immune selection, and absence of detectable clade switching in reinfections indicates initial exposure was insufficient to elicit a protective immune response.",2018 Jun 1,"['Kiyuka, Patience K', 'Agoti, Charles N', 'Munywoki, Patrick K', 'Njeru, Regina', 'Bett, Anne', 'Otieno, James R', 'Otieno, Grieven P', 'Kamau, Everlyn', 'Clark, Taane G', 'van der Hoek, Lia', 'Kellam, Paul', 'Nokes, D James', 'Cotten, Matthew']",J Infect Dis,,,False
51384d997f8349402f814dd623dd221b6769117c,PMC,Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya,http://dx.doi.org/10.1093/infdis/jiy098,PMC6037089,29741740,CC BY,"BACKGROUND: Human coronavirus NL63 (HCoV-NL63) is a globally endemic pathogen causing mild and severe respiratory tract infections with reinfections occurring repeatedly throughout a lifetime. METHODS: Nasal samples were collected in coastal Kenya through community-based and hospital-based surveillance. HCoV-NL63 was detected with multiplex real-time reverse transcription PCR, and positive samples were targeted for nucleotide sequencing of the spike (S) protein. Additionally, paired samples from 25 individuals with evidence of repeat HCoV-NL63 infection were selected for whole-genome virus sequencing. RESULTS: HCoV-NL63 was detected in 1.3% (75/5573) of child pneumonia admissions. Two HCoV-NL63 genotypes circulated in Kilifi between 2008 and 2014. Full genome sequences formed a monophyletic clade closely related to contemporary HCoV-NL63 from other global locations. An unexpected pattern of repeat infections was observed with some individuals showing higher viral titers during their second infection. Similar patterns for 2 other endemic coronaviruses, HCoV-229E and HCoV-OC43, were observed. Repeat infections by HCoV-NL63 were not accompanied by detectable genotype switching. CONCLUSIONS: In this coastal Kenya setting, HCoV-NL63 exhibited low prevalence in hospital pediatric pneumonia admissions. Clade persistence with low genetic diversity suggest limited immune selection, and absence of detectable clade switching in reinfections indicates initial exposure was insufficient to elicit a protective immune response.",2018 Jun 1,"['Kiyuka, Patience K', 'Agoti, Charles N', 'Munywoki, Patrick K', 'Njeru, Regina', 'Bett, Anne', 'Otieno, James R', 'Otieno, Grieven P', 'Kamau, Everlyn', 'Clark, Taane G', 'van der Hoek, Lia', 'Kellam, Paul', 'Nokes, D James', 'Cotten, Matthew']",J Infect Dis,,,False
76a1894ee3ade28e1fd11edd750b988c81ad459b,PMC,Prevalence of chronic comorbidities in dengue fever and West Nile virus: A systematic review and meta-analysis,http://dx.doi.org/10.1371/journal.pone.0200200,PMC6039036,29990356,CC BY,"BACKGROUND: Flavivirus diseases such as dengue fever (DENV), West Nile virus (WNV), Zika and yellow fever represent a substantial global public health concern. Preexisting chronic conditions such as cardiovascular diseases, diabetes, obesity, and asthma were thought to predict risk of progression to severe infections. OBJECTIVE: We aimed to quantify the frequency of chronic comorbidities in flavivirus diseases to provide an estimate for their prevalence in severe and non-severe infections and examine whether chronic diseases contribute to the increased risk of severe viral expression. METHODS: We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic and grey literature databases to identify studies reporting prevalence estimates of comorbidities in flavivirus diseases. Study quality was assessed with the risk of bias tool. Age-adjusted odds ratios (ORs) were estimated for severe infection in the presence of chronic comorbidities. RESULTS: We identified 65 studies as eligible for inclusion for DENV (47 studies) and WNV (18 studies). Obesity and overweight (i.e., BMI> 25 kg/m(2), prevalence: 24.5%, 95% CI: 18.6–31.6%), hypertension (17.1%, 13.3–21.8%) and diabetes (13.3%, 9.3–18.8%) were the most prevalent comorbidities in DENV. However, hypertension (45.0%, 39.1–51.0%), diabetes (24.7%, 20.2–29.8%) and heart diseases (25.6%, 19.5–32.7%) were the most prevalent in WNV. ORs of severe flavivirus diseases were about 2 to 4 in infected patients with comorbidities such as diabetes, hypertension and heart diseases. The small number of studies in JEV, YFV and Zika did not permit estimating the prevalence of comorbidities in these infections. CONCLUSION: Higher prevalence of chronic comorbidities was found in severe cases of flavivirus diseases compared to non-severe cases. Findings of the present study may guide public health practitioners and clinicians to evaluate infection severity based on the presence of comorbidity, a critical public health measure that may avert severe disease outcome given the current dearth of clear prevention practices for some flavivirus diseases.",2018 Jul 10,"['Badawi, Alaa', 'Velummailum, Russanthy', 'Ryoo, Seung Gwan', 'Senthinathan, Arrani', 'Yaghoubi, Sahar', 'Vasileva, Denitsa', 'Ostermeier, Emma', 'Plishka, Mikayla', 'Soosaipillai, Marcel', 'Arora, Paul']",PLoS One,,,True
b20c6ac4f221e5b34acf7899f2a032b3e836843d,PMC,Prevalence of chronic comorbidities in dengue fever and West Nile virus: A systematic review and meta-analysis,http://dx.doi.org/10.1371/journal.pone.0200200,PMC6039036,29990356,CC BY,"BACKGROUND: Flavivirus diseases such as dengue fever (DENV), West Nile virus (WNV), Zika and yellow fever represent a substantial global public health concern. Preexisting chronic conditions such as cardiovascular diseases, diabetes, obesity, and asthma were thought to predict risk of progression to severe infections. OBJECTIVE: We aimed to quantify the frequency of chronic comorbidities in flavivirus diseases to provide an estimate for their prevalence in severe and non-severe infections and examine whether chronic diseases contribute to the increased risk of severe viral expression. METHODS: We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic and grey literature databases to identify studies reporting prevalence estimates of comorbidities in flavivirus diseases. Study quality was assessed with the risk of bias tool. Age-adjusted odds ratios (ORs) were estimated for severe infection in the presence of chronic comorbidities. RESULTS: We identified 65 studies as eligible for inclusion for DENV (47 studies) and WNV (18 studies). Obesity and overweight (i.e., BMI> 25 kg/m(2), prevalence: 24.5%, 95% CI: 18.6–31.6%), hypertension (17.1%, 13.3–21.8%) and diabetes (13.3%, 9.3–18.8%) were the most prevalent comorbidities in DENV. However, hypertension (45.0%, 39.1–51.0%), diabetes (24.7%, 20.2–29.8%) and heart diseases (25.6%, 19.5–32.7%) were the most prevalent in WNV. ORs of severe flavivirus diseases were about 2 to 4 in infected patients with comorbidities such as diabetes, hypertension and heart diseases. The small number of studies in JEV, YFV and Zika did not permit estimating the prevalence of comorbidities in these infections. CONCLUSION: Higher prevalence of chronic comorbidities was found in severe cases of flavivirus diseases compared to non-severe cases. Findings of the present study may guide public health practitioners and clinicians to evaluate infection severity based on the presence of comorbidity, a critical public health measure that may avert severe disease outcome given the current dearth of clear prevention practices for some flavivirus diseases.",2018 Jul 10,"['Badawi, Alaa', 'Velummailum, Russanthy', 'Ryoo, Seung Gwan', 'Senthinathan, Arrani', 'Yaghoubi, Sahar', 'Vasileva, Denitsa', 'Ostermeier, Emma', 'Plishka, Mikayla', 'Soosaipillai, Marcel', 'Arora, Paul']",PLoS One,,,False
510e8eb06ab57f34527439e6bcc1c486b82da1ac,PMC,Prevalence of chronic comorbidities in dengue fever and West Nile virus: A systematic review and meta-analysis,http://dx.doi.org/10.1371/journal.pone.0200200,PMC6039036,29990356,CC BY,"BACKGROUND: Flavivirus diseases such as dengue fever (DENV), West Nile virus (WNV), Zika and yellow fever represent a substantial global public health concern. Preexisting chronic conditions such as cardiovascular diseases, diabetes, obesity, and asthma were thought to predict risk of progression to severe infections. OBJECTIVE: We aimed to quantify the frequency of chronic comorbidities in flavivirus diseases to provide an estimate for their prevalence in severe and non-severe infections and examine whether chronic diseases contribute to the increased risk of severe viral expression. METHODS: We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic and grey literature databases to identify studies reporting prevalence estimates of comorbidities in flavivirus diseases. Study quality was assessed with the risk of bias tool. Age-adjusted odds ratios (ORs) were estimated for severe infection in the presence of chronic comorbidities. RESULTS: We identified 65 studies as eligible for inclusion for DENV (47 studies) and WNV (18 studies). Obesity and overweight (i.e., BMI> 25 kg/m(2), prevalence: 24.5%, 95% CI: 18.6–31.6%), hypertension (17.1%, 13.3–21.8%) and diabetes (13.3%, 9.3–18.8%) were the most prevalent comorbidities in DENV. However, hypertension (45.0%, 39.1–51.0%), diabetes (24.7%, 20.2–29.8%) and heart diseases (25.6%, 19.5–32.7%) were the most prevalent in WNV. ORs of severe flavivirus diseases were about 2 to 4 in infected patients with comorbidities such as diabetes, hypertension and heart diseases. The small number of studies in JEV, YFV and Zika did not permit estimating the prevalence of comorbidities in these infections. CONCLUSION: Higher prevalence of chronic comorbidities was found in severe cases of flavivirus diseases compared to non-severe cases. Findings of the present study may guide public health practitioners and clinicians to evaluate infection severity based on the presence of comorbidity, a critical public health measure that may avert severe disease outcome given the current dearth of clear prevention practices for some flavivirus diseases.",2018 Jul 10,"['Badawi, Alaa', 'Velummailum, Russanthy', 'Ryoo, Seung Gwan', 'Senthinathan, Arrani', 'Yaghoubi, Sahar', 'Vasileva, Denitsa', 'Ostermeier, Emma', 'Plishka, Mikayla', 'Soosaipillai, Marcel', 'Arora, Paul']",PLoS One,,,False
32d011e8c6c577684d160d7b0ffd6ec29dc0032c,PMC,Prevalence of chronic comorbidities in dengue fever and West Nile virus: A systematic review and meta-analysis,http://dx.doi.org/10.1371/journal.pone.0200200,PMC6039036,29990356,CC BY,"BACKGROUND: Flavivirus diseases such as dengue fever (DENV), West Nile virus (WNV), Zika and yellow fever represent a substantial global public health concern. Preexisting chronic conditions such as cardiovascular diseases, diabetes, obesity, and asthma were thought to predict risk of progression to severe infections. OBJECTIVE: We aimed to quantify the frequency of chronic comorbidities in flavivirus diseases to provide an estimate for their prevalence in severe and non-severe infections and examine whether chronic diseases contribute to the increased risk of severe viral expression. METHODS: We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic and grey literature databases to identify studies reporting prevalence estimates of comorbidities in flavivirus diseases. Study quality was assessed with the risk of bias tool. Age-adjusted odds ratios (ORs) were estimated for severe infection in the presence of chronic comorbidities. RESULTS: We identified 65 studies as eligible for inclusion for DENV (47 studies) and WNV (18 studies). Obesity and overweight (i.e., BMI> 25 kg/m(2), prevalence: 24.5%, 95% CI: 18.6–31.6%), hypertension (17.1%, 13.3–21.8%) and diabetes (13.3%, 9.3–18.8%) were the most prevalent comorbidities in DENV. However, hypertension (45.0%, 39.1–51.0%), diabetes (24.7%, 20.2–29.8%) and heart diseases (25.6%, 19.5–32.7%) were the most prevalent in WNV. ORs of severe flavivirus diseases were about 2 to 4 in infected patients with comorbidities such as diabetes, hypertension and heart diseases. The small number of studies in JEV, YFV and Zika did not permit estimating the prevalence of comorbidities in these infections. CONCLUSION: Higher prevalence of chronic comorbidities was found in severe cases of flavivirus diseases compared to non-severe cases. Findings of the present study may guide public health practitioners and clinicians to evaluate infection severity based on the presence of comorbidity, a critical public health measure that may avert severe disease outcome given the current dearth of clear prevention practices for some flavivirus diseases.",2018 Jul 10,"['Badawi, Alaa', 'Velummailum, Russanthy', 'Ryoo, Seung Gwan', 'Senthinathan, Arrani', 'Yaghoubi, Sahar', 'Vasileva, Denitsa', 'Ostermeier, Emma', 'Plishka, Mikayla', 'Soosaipillai, Marcel', 'Arora, Paul']",PLoS One,,,False
9ad5d78b00aad1f5a796c970a8b825f273e6f735,PMC,Prevalence of chronic comorbidities in dengue fever and West Nile virus: A systematic review and meta-analysis,http://dx.doi.org/10.1371/journal.pone.0200200,PMC6039036,29990356,CC BY,"BACKGROUND: Flavivirus diseases such as dengue fever (DENV), West Nile virus (WNV), Zika and yellow fever represent a substantial global public health concern. Preexisting chronic conditions such as cardiovascular diseases, diabetes, obesity, and asthma were thought to predict risk of progression to severe infections. OBJECTIVE: We aimed to quantify the frequency of chronic comorbidities in flavivirus diseases to provide an estimate for their prevalence in severe and non-severe infections and examine whether chronic diseases contribute to the increased risk of severe viral expression. METHODS: We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic and grey literature databases to identify studies reporting prevalence estimates of comorbidities in flavivirus diseases. Study quality was assessed with the risk of bias tool. Age-adjusted odds ratios (ORs) were estimated for severe infection in the presence of chronic comorbidities. RESULTS: We identified 65 studies as eligible for inclusion for DENV (47 studies) and WNV (18 studies). Obesity and overweight (i.e., BMI> 25 kg/m(2), prevalence: 24.5%, 95% CI: 18.6–31.6%), hypertension (17.1%, 13.3–21.8%) and diabetes (13.3%, 9.3–18.8%) were the most prevalent comorbidities in DENV. However, hypertension (45.0%, 39.1–51.0%), diabetes (24.7%, 20.2–29.8%) and heart diseases (25.6%, 19.5–32.7%) were the most prevalent in WNV. ORs of severe flavivirus diseases were about 2 to 4 in infected patients with comorbidities such as diabetes, hypertension and heart diseases. The small number of studies in JEV, YFV and Zika did not permit estimating the prevalence of comorbidities in these infections. CONCLUSION: Higher prevalence of chronic comorbidities was found in severe cases of flavivirus diseases compared to non-severe cases. Findings of the present study may guide public health practitioners and clinicians to evaluate infection severity based on the presence of comorbidity, a critical public health measure that may avert severe disease outcome given the current dearth of clear prevention practices for some flavivirus diseases.",2018 Jul 10,"['Badawi, Alaa', 'Velummailum, Russanthy', 'Ryoo, Seung Gwan', 'Senthinathan, Arrani', 'Yaghoubi, Sahar', 'Vasileva, Denitsa', 'Ostermeier, Emma', 'Plishka, Mikayla', 'Soosaipillai, Marcel', 'Arora, Paul']",PLoS One,,,False
59cdfbf3b9e99d780b3ad6cf2985e34ec61e8f5a,PMC,A speed–fidelity trade-off determines the mutation rate and virulence of an RNA virus,http://dx.doi.org/10.1371/journal.pbio.2006459,PMC6040757,29953453,CC BY,"Mutation rates can evolve through genetic drift, indirect selection due to genetic hitchhiking, or direct selection on the physicochemical cost of high fidelity. However, for many systems, it has been difficult to disentangle the relative impact of these forces empirically. In RNA viruses, an observed correlation between mutation rate and virulence has led many to argue that their extremely high mutation rates are advantageous because they may allow for increased adaptability. This argument has profound implications because it suggests that pathogenesis in many viral infections depends on rare or de novo mutations. Here, we present data for an alternative model whereby RNA viruses evolve high mutation rates as a byproduct of selection for increased replicative speed. We find that a poliovirus antimutator, 3D(G64S), has a significant replication defect and that wild-type (WT) and 3D(G64S) populations have similar adaptability in 2 distinct cellular environments. Experimental evolution of 3D(G64S) under selection for replicative speed led to reversion and compensation of the fidelity phenotype. Mice infected with 3D(G64S) exhibited delayed morbidity at doses well above the lethal level, consistent with attenuation by slower growth as opposed to reduced mutational supply. Furthermore, compensation of the 3D(G64S) growth defect restored virulence, while compensation of the fidelity phenotype did not. Our data are consistent with the kinetic proofreading model for biosynthetic reactions and suggest that speed is more important than accuracy. In contrast with what has been suggested for many RNA viruses, we find that within-host spread is associated with viral replicative speed and not standing genetic diversity.",2018 Jun 28,"['Fitzsimmons, William J.', 'Woods, Robert J.', 'McCrone, John T.', 'Woodman, Andrew', 'Arnold, Jamie J.', 'Yennawar, Madhumita', 'Evans, Richard', 'Cameron, Craig E.', 'Lauring, Adam S.']",PLoS Biol,,,True
f1708259b43bdfaecb73392ecd9d1a9749970269,PMC,A speed–fidelity trade-off determines the mutation rate and virulence of an RNA virus,http://dx.doi.org/10.1371/journal.pbio.2006459,PMC6040757,29953453,CC BY,"Mutation rates can evolve through genetic drift, indirect selection due to genetic hitchhiking, or direct selection on the physicochemical cost of high fidelity. However, for many systems, it has been difficult to disentangle the relative impact of these forces empirically. In RNA viruses, an observed correlation between mutation rate and virulence has led many to argue that their extremely high mutation rates are advantageous because they may allow for increased adaptability. This argument has profound implications because it suggests that pathogenesis in many viral infections depends on rare or de novo mutations. Here, we present data for an alternative model whereby RNA viruses evolve high mutation rates as a byproduct of selection for increased replicative speed. We find that a poliovirus antimutator, 3D(G64S), has a significant replication defect and that wild-type (WT) and 3D(G64S) populations have similar adaptability in 2 distinct cellular environments. Experimental evolution of 3D(G64S) under selection for replicative speed led to reversion and compensation of the fidelity phenotype. Mice infected with 3D(G64S) exhibited delayed morbidity at doses well above the lethal level, consistent with attenuation by slower growth as opposed to reduced mutational supply. Furthermore, compensation of the 3D(G64S) growth defect restored virulence, while compensation of the fidelity phenotype did not. Our data are consistent with the kinetic proofreading model for biosynthetic reactions and suggest that speed is more important than accuracy. In contrast with what has been suggested for many RNA viruses, we find that within-host spread is associated with viral replicative speed and not standing genetic diversity.",2018 Jun 28,"['Fitzsimmons, William J.', 'Woods, Robert J.', 'McCrone, John T.', 'Woodman, Andrew', 'Arnold, Jamie J.', 'Yennawar, Madhumita', 'Evans, Richard', 'Cameron, Craig E.', 'Lauring, Adam S.']",PLoS Biol,,,False
7d6c760305ccab69a78896e4e7000dd88c53eb96,PMC,A speed–fidelity trade-off determines the mutation rate and virulence of an RNA virus,http://dx.doi.org/10.1371/journal.pbio.2006459,PMC6040757,29953453,CC BY,"Mutation rates can evolve through genetic drift, indirect selection due to genetic hitchhiking, or direct selection on the physicochemical cost of high fidelity. However, for many systems, it has been difficult to disentangle the relative impact of these forces empirically. In RNA viruses, an observed correlation between mutation rate and virulence has led many to argue that their extremely high mutation rates are advantageous because they may allow for increased adaptability. This argument has profound implications because it suggests that pathogenesis in many viral infections depends on rare or de novo mutations. Here, we present data for an alternative model whereby RNA viruses evolve high mutation rates as a byproduct of selection for increased replicative speed. We find that a poliovirus antimutator, 3D(G64S), has a significant replication defect and that wild-type (WT) and 3D(G64S) populations have similar adaptability in 2 distinct cellular environments. Experimental evolution of 3D(G64S) under selection for replicative speed led to reversion and compensation of the fidelity phenotype. Mice infected with 3D(G64S) exhibited delayed morbidity at doses well above the lethal level, consistent with attenuation by slower growth as opposed to reduced mutational supply. Furthermore, compensation of the 3D(G64S) growth defect restored virulence, while compensation of the fidelity phenotype did not. Our data are consistent with the kinetic proofreading model for biosynthetic reactions and suggest that speed is more important than accuracy. In contrast with what has been suggested for many RNA viruses, we find that within-host spread is associated with viral replicative speed and not standing genetic diversity.",2018 Jun 28,"['Fitzsimmons, William J.', 'Woods, Robert J.', 'McCrone, John T.', 'Woodman, Andrew', 'Arnold, Jamie J.', 'Yennawar, Madhumita', 'Evans, Richard', 'Cameron, Craig E.', 'Lauring, Adam S.']",PLoS Biol,,,False
e92ca74ee6c3ac082781a3adaa3088c15e6915e3,PMC,A speed–fidelity trade-off determines the mutation rate and virulence of an RNA virus,http://dx.doi.org/10.1371/journal.pbio.2006459,PMC6040757,29953453,CC BY,"Mutation rates can evolve through genetic drift, indirect selection due to genetic hitchhiking, or direct selection on the physicochemical cost of high fidelity. However, for many systems, it has been difficult to disentangle the relative impact of these forces empirically. In RNA viruses, an observed correlation between mutation rate and virulence has led many to argue that their extremely high mutation rates are advantageous because they may allow for increased adaptability. This argument has profound implications because it suggests that pathogenesis in many viral infections depends on rare or de novo mutations. Here, we present data for an alternative model whereby RNA viruses evolve high mutation rates as a byproduct of selection for increased replicative speed. We find that a poliovirus antimutator, 3D(G64S), has a significant replication defect and that wild-type (WT) and 3D(G64S) populations have similar adaptability in 2 distinct cellular environments. Experimental evolution of 3D(G64S) under selection for replicative speed led to reversion and compensation of the fidelity phenotype. Mice infected with 3D(G64S) exhibited delayed morbidity at doses well above the lethal level, consistent with attenuation by slower growth as opposed to reduced mutational supply. Furthermore, compensation of the 3D(G64S) growth defect restored virulence, while compensation of the fidelity phenotype did not. Our data are consistent with the kinetic proofreading model for biosynthetic reactions and suggest that speed is more important than accuracy. In contrast with what has been suggested for many RNA viruses, we find that within-host spread is associated with viral replicative speed and not standing genetic diversity.",2018 Jun 28,"['Fitzsimmons, William J.', 'Woods, Robert J.', 'McCrone, John T.', 'Woodman, Andrew', 'Arnold, Jamie J.', 'Yennawar, Madhumita', 'Evans, Richard', 'Cameron, Craig E.', 'Lauring, Adam S.']",PLoS Biol,,,False
58d1eab77cf8a541864220d8b3130336881891b7,PMC,"Presumed Caudal Cerebellar Artery Infarction in Three Cats: Neurological Signs, MRI Findings, and Outcome",http://dx.doi.org/10.3389/fvets.2018.00155,PMC6041406,30027093,CC BY,"Ischemic cerebrovascular disease (CVD) is a relatively common condition in dogs but infrequent in cats, with acute or peracute onset of non-progressive neurological signs. Cerebellar artery infarction appears to be very uncommon in cats, with only two cases reported affecting the rostral cerebellar artery (RCA). This study aims to report for the first time the neurological signs, magnetic resonance imaging (MRI) findings and outcome in three cats diagnosed with presumed caudal cerebellar artery (CCA) infarction. Unique presentation of vestibular signs associated with CCA in three cats and similarities between dogs and humans are discussed.",2018 Jul 5,"['Negrin, Arianna', 'Taeymans, Olivier N. J.', 'Spencer, Sarah E.', 'Cherubini, Giunio B.']",Front Vet Sci,,,True
7ffbca7e7e60e13461801769ad70f770879d0f81,PMC,Asymptomatic Shedding of Respiratory Virus among an Ambulatory Population across Seasons,http://dx.doi.org/10.1128/mSphere.00249-18,PMC6041500,29997120,CC BY,"Most observation of human respiratory virus carriage is derived from medical surveillance; however, the infections documented by this surveillance represent only a symptomatic fraction of the total infected population. As the role of asymptomatic infection in respiratory virus transmission is still largely unknown and rates of asymptomatic shedding are not well constrained, it is important to obtain more-precise estimates through alternative sampling methods. We actively recruited participants from among visitors to a New York City tourist attraction. Nasopharyngeal swabs, demographics, and survey information on symptoms, medical history, and recent travel were obtained from 2,685 adults over two seasonal arms. We used multiplex PCR to test swab specimens for a selection of common respiratory viruses. A total of 6.2% of samples (168 individuals) tested positive for at least one virus, with 5.6% testing positive in the summer arm and 7.0% testing positive in the winter arm. Of these, 85 (50.6%) were positive for human rhinovirus (HRV), 65 (38.7%) for coronavirus (CoV), and 18 (10.2%) for other viruses (including adenovirus, human metapneumovirus, influenza virus, and parainfluenza virus). Depending on the definition of symptomatic infection, 65% to 97% of infections were classified as asymptomatic. The best-fit model for prediction of positivity across all viruses included a symptom severity score, Hispanic ethnicity data, and age category, though there were slight differences across the seasonal arms. Though having symptoms is predictive of virus positivity, there are high levels of asymptomatic respiratory virus shedding among the members of an ambulatory population in New York City. IMPORTANCE Respiratory viruses are common in human populations, causing significant levels of morbidity. Understanding the distribution of these viruses is critical for designing control methods. However, most data available are from medical records and thus predominantly represent symptomatic infections. Estimates for asymptomatic prevalence are sparse and span a broad range. In this study, we aimed to measure more precisely the proportion of infections that are asymptomatic in a general, ambulatory adult population. We recruited participants from a New York City tourist attraction and administered nasal swabs, testing them for adenovirus, coronavirus, human metapneumovirus, rhinovirus, influenza virus, respiratory syncytial virus, and parainfluenza virus. At recruitment, participants completed surveys on demographics and symptomology. Analysis of these data indicated that over 6% of participants tested positive for shedding of respiratory virus. While participants who tested positive were more likely to report symptoms than those who did not, over half of participants who tested positive were asymptomatic.",2018 Jul 11,"['Birger, Ruthie', 'Morita, Haruka', 'Comito, Devon', 'Filip, Ioan', 'Galanti, Marta', 'Lane, Benjamin', 'Ligon, Chanel', 'Rosenbloom, Daniel', 'Shittu, Atinuke', 'Ud-Dean, Minhaz', 'Desalle, Rob', 'Planet, Paul', 'Shaman, Jeffrey']",mSphere,,,True
7f67a850db06d9b9e3f63d9943e2b1fc5a72ca8f,PMC,Illuminating pathogen–host intimacy through optogenetics,http://dx.doi.org/10.1371/journal.ppat.1007046,PMC6042787,30001435,CC BY,"The birth and subsequent evolution of optogenetics has resulted in an unprecedented advancement in our understanding of the brain. Its outstanding success does usher wider applications; however, the tool remains still largely relegated to neuroscience. Here, we introduce selected aspects of optogenetics with potential applications in infection biology that will not only answer long-standing questions about intracellular pathogens (parasites, bacteria, viruses) but also broaden the dimension of current research in entwined models. In this essay, we illustrate how a judicious integration of optogenetics with routine methods can illuminate the host–pathogen interactions in a way that has not been feasible otherwise.",2018 Jul 12,"['Arroyo-Olarte, Ruben Dario', 'Thurow, Laura', 'Kozjak-Pavlovic, Vera', 'Gupta, Nishith']",PLoS Pathog,,,True
5e2d43ab82c3b7067647694fce9addeaea87c0a9,PMC,Illuminating pathogen–host intimacy through optogenetics,http://dx.doi.org/10.1371/journal.ppat.1007046,PMC6042787,30001435,CC BY,"The birth and subsequent evolution of optogenetics has resulted in an unprecedented advancement in our understanding of the brain. Its outstanding success does usher wider applications; however, the tool remains still largely relegated to neuroscience. Here, we introduce selected aspects of optogenetics with potential applications in infection biology that will not only answer long-standing questions about intracellular pathogens (parasites, bacteria, viruses) but also broaden the dimension of current research in entwined models. In this essay, we illustrate how a judicious integration of optogenetics with routine methods can illuminate the host–pathogen interactions in a way that has not been feasible otherwise.",2018 Jul 12,"['Arroyo-Olarte, Ruben Dario', 'Thurow, Laura', 'Kozjak-Pavlovic, Vera', 'Gupta, Nishith']",PLoS Pathog,,,False
dd916c3ebb297ef2b6a36f7d6f33bac8ed1198b8,PMC,Development of rapid guidelines: 1. Systematic survey of current practices and methods,http://dx.doi.org/10.1186/s12961-018-0327-8,PMC6044042,30005712,CC BY,"BACKGROUND: Guidelines in the healthcare field generally should contain evidence-based recommendations to inform healthcare decisions. Guidelines often require 2 years or more to develop, but certain circumstances necessitate the development of rapid guidelines (RGs) in a short period of time. Upholding methodological rigor while meeting the reduced development timeframe presents a challenge for developing RGs. Our objective was to review current practices and standards for the development of RGs. This is the first of a series of three articles addressing methodological issues around RGs. METHODS: We conducted a systematic survey of methods manuals and published RGs to identify reasons for the development of RGs. Data sources included existing guideline manuals, published RGs, Trip Medical Database, MEDLINE, EMBASE and communication with guideline developers until February 2018. RESULTS: We identified 46 guidelines that used a shortened timeframe for their development. Nomenclature describing RGs varied across organisations, wherein the United States Centers for Disease Control and Prevention produced ‘Interim Guidelines’, the National Institute for Health and Care Excellence in the United Kingdom developed ‘Short Clinical Guidelines’, and WHO provided ‘Rapid Advice’. The rationale for RGs included response to emergencies, rapid increases in cases of a condition or disease severity, or new evidence regarding treatment. In general, the methods to assess the quality of evidence, the consensus process and the management of the conflict of interest were not always clear. While we identified another 11 RGs from other institutions, there was no reference to timeframe and reasons for conducting a RG. The three organisations mentioned above provide guidance for the development of RGs. CONCLUSIONS: There is a lack of standardised nomenclature and definitions regarding RGs and there is inconsistency in the methods described in manuals and in RG. It is therefore important that all RGs provide a detailed and transparent description of their methods in order for readers and end-users to be able to assess their quality and validate their findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12961-018-0327-8) contains supplementary material, which is available to authorized users.",2018 Jul 13,"['Kowalski, Sergio C.', 'Morgan, Rebecca L.', 'Falavigna, Maicon', 'Florez, Iván D.', 'Etxeandia-Ikobaltzeta, Itziar', 'Wiercioch, Wojtek', 'Zhang, Yuan', 'Sakhia, Faria', 'Ivanova, Liudmila', 'Santesso, Nancy', 'Schünemann, Holger J.']",Health Res Policy Syst,,,True
8808dc1135689cb864eb28ea3e5d8da320d8b225,PMC,"The Impacts on Health, Society, and Economy of SARS and H7N9 Outbreaks in China: A Case Comparison Study",http://dx.doi.org/10.1155/2018/2710185,PMC6046118,30050581,CC BY,"BACKGROUND: Epidemics such as SARS and H7N9 have caused huge negative impacts on population health and the economy in China. AIMS: This article discusses the impacts of SARS in 2003 and H7N9 in 2013 in China, in order to provide a better understanding to government and practitioners of why improving management of response to infectious disease outbreaks is so critical for a country's economy, its society, and its place in the global community. METHODS: To provide the results of an analysis of impacts of SARS and H7N9 based on feedback from documents, informants, and focus groups on events during the SARS and H7N9 outbreaks. RESULTS: Both outbreaks of SARS and H7N9 have had an impact on China, causing significant negative impacts on health, the economy, and even national and even international security. CONCLUSIONS: Both SARS coronavirus and H7N9 viruses presented a global epidemic threat, but the social and economic impacts of H7N9 were not as serious as in the case of SARS because the response to H7N9 was more effective.",2018 Jun 28,"['Qiu, Wuqi', 'Chu, Cordia', 'Mao, Ayan', 'Wu, Jing']",J Environ Public Health,,,True
7b43bc93643486d9f95f4523dbda00d6252ae13d,PMC,A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques,http://dx.doi.org/10.1038/s41598-018-28900-1,PMC6048037,30013082,CC BY,"The recurrence of new human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) underscores the need for effective therapeutic countermeasures. Nonhuman primate models are considered the gold standard for preclinical evaluation of therapeutic countermeasures. However, MERS-CoV-induced severe respiratory disease in humans is associated with high viral loads in the lower respiratory tract, which may be difficult to achieve in nonhuman primate models. Considering this limitation, we wanted to ascertain the effectiveness of using a MERS-CoV infectious clone (icMERS-0) previously shown to replicate to higher titers than the wild-type EMC 2012 strain. We observed respiratory disease resulting from exposure to the icMERS-0 strain as measured by CT in rhesus monkeys with concomitant detection of virus antigen by immunohistochemistry. Overall, respiratory disease was mild and transient, resolving by day 30 post-infection. Although pulmonary disease was mild, these results demonstrate for the first time the utility of CT imaging to measure disease elicited by a MERS-CoV infectious clone system in nonhuman primate models.",2018 Jul 16,"['Cockrell, Adam S.', 'Johnson, Joshua C.', 'Moore, Ian N.', 'Liu, David X.', 'Bock, Kevin W.', 'Douglas, Madeline G.', 'Graham, Rachel L.', 'Solomon, Jeffrey', 'Torzewski, Lisa', 'Bartos, Christopher', 'Hart, Randy', 'Baric, Ralph S.', 'Johnson, Reed F.']",Sci Rep,,,False
e835b6338e31398a5abaca8548b69da8e19b61d5,PMC,A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques,http://dx.doi.org/10.1038/s41598-018-28900-1,PMC6048037,30013082,CC BY,"The recurrence of new human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) underscores the need for effective therapeutic countermeasures. Nonhuman primate models are considered the gold standard for preclinical evaluation of therapeutic countermeasures. However, MERS-CoV-induced severe respiratory disease in humans is associated with high viral loads in the lower respiratory tract, which may be difficult to achieve in nonhuman primate models. Considering this limitation, we wanted to ascertain the effectiveness of using a MERS-CoV infectious clone (icMERS-0) previously shown to replicate to higher titers than the wild-type EMC 2012 strain. We observed respiratory disease resulting from exposure to the icMERS-0 strain as measured by CT in rhesus monkeys with concomitant detection of virus antigen by immunohistochemistry. Overall, respiratory disease was mild and transient, resolving by day 30 post-infection. Although pulmonary disease was mild, these results demonstrate for the first time the utility of CT imaging to measure disease elicited by a MERS-CoV infectious clone system in nonhuman primate models.",2018 Jul 16,"['Cockrell, Adam S.', 'Johnson, Joshua C.', 'Moore, Ian N.', 'Liu, David X.', 'Bock, Kevin W.', 'Douglas, Madeline G.', 'Graham, Rachel L.', 'Solomon, Jeffrey', 'Torzewski, Lisa', 'Bartos, Christopher', 'Hart, Randy', 'Baric, Ralph S.', 'Johnson, Reed F.']",Sci Rep,,,True
a04811d55a6f779546cf0c2bf5d46982fb989908,PMC,"Preliminary study on the tick population of Benin wildlife at the moment of its invasion by the Rhipicephalus microplus tick (Canestrini, 1888)",http://dx.doi.org/10.14202/vetworld.2018.845-851,PMC6048076,30034180,CC BY,"BACKGROUND AND AIM: Rhipicephalus microplus (Rm) is one of the most problematic livestock tick species in the world. Its rapid propagation and resistance to acaricides make it control difficult in the sub-region and Benin particularly. The aim of this work was to check its presence in wildlife and to confirm the possible role of reservoir wildlife may play in the propagation of the parasite. This will help to design more efficient control strategy. MATERIALS AND METHODS: This study was conducted from February to March 2017 in the National Parks of Benin (Pendjari and W Park) and wildfowl’s assembly and selling point in Benin. Ticks were manually picked with forceps from each animal after slaughtering by hunters then stored in 70° ethanol. Collected ticks were counted and identified in the laboratory using the identification key as described by Walker. RESULTS: Overall, seven species of ticks (Amblyomma variegatum, Boophilus decoloratus, Rm, Boophilus spp., Hyalomma spp., Rhipicephalus sanguineus, Rhipicephalus spp.) were identified on nine wild animal species sampled (Cane rat, wildcat, Hare, Doe, Cricetoma, Buffalo, Buffon Cobe, and Bushbuck and Warthog). The average number of ticks varies from 3 to 6 between animal species, 3 to 7 between localities visited, and 2 to 5 between tick species. However, these differences are statistically significant only for localities. Considering tick species and animal species, the parasite load of Rm and Rhipicephalus spp. is higher; the buffalo being more infested. The analysis of deviance reveals that the abundance of ticks observed depends only on the observed localities (p>0.05). However, the interactions between animal species and localities on the one hand and between animal and tick species on the other hand, although not significant, have influenced the abundance of ticks as they reduce the residual deviance after their inclusion in the model. CONCLUSIONS: This study reported the presence of Rm in wildlife of Benin and confirmed its role in the maintenance and spread of the parasites. It is, therefore, an important risk factor that we must not neglect in the epidemiological surveillance and ticks control strategies in the West African sub-region and particularly in Benin.",2018 Jun 25,"['Adinci, Kossi Justin', 'Akpo, Yao', 'Adoligbe, Camus', 'Adehan, Safiou Bienvenu', 'Yessinou, Roland Eric', 'Sodé, Akoeugnigan Idelphonse', 'Mensah, Guy Appolinaire', 'Youssao, Abdou Karim Issaka', 'Sinsin, Brice', 'Farougou, Souaïbou']",Vet World,,,True
cabe6a81b684ef3c7b8febdc093f1aacbe06ced6,PMC,Advancements in Host-Based Interventions for Influenza Treatment,http://dx.doi.org/10.3389/fimmu.2018.01547,PMC6048202,30042762,CC BY,"Influenza is a major acute respiratory infection that causes mortality and morbidity worldwide. Two classes of conventional antivirals, M2 ion channel blockers and neuraminidase inhibitors, are mainstays in managing influenza disease to lessen symptoms while minimizing hospitalization and death in patients with severe influenza. However, the development of viral resistance to both drug classes has become a major public health concern. Vaccines are prophylaxis mainstays but are limited in efficacy due to the difficulty in matching predicted dominant viral strains to circulating strains. As such, other potential interventions are being explored. Since viruses rely on host cellular functions to replicate, recent therapeutic developments focus on targeting host factors involved in virus replication. Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. In this review, we will discuss the advancements in novel host-based interventions for treating influenza disease.",2018 Jul 10,"['Yip, Tsz-Fung', 'Selim, Aisha Sami Mohammed', 'Lian, Ida', 'Lee, Suki Man-Yan']",Front Immunol,,,True
f2f78c95ab378a31bd35dc1de84e0ec75eb7ce1b,PMC,Epidemiology of HBoV1 infection and relationship with meteorological conditions in hospitalized pediatric patients with acute respiratory illness: a 7-year study in a subtropical region,http://dx.doi.org/10.1186/s12879-018-3225-3,PMC6048719,30012099,CC BY,"BACKGROUND: Human bocavirus 1 (HBoV1) is an important cause of acute respiratory illness (ARI), yet the epidemiology and effect of meteorological conditions on infection is not fully understood. To investigate the distribution of HBoV1 and determine the effect of meteorological conditions, hospitalized pediatric patients were studied in a subtropical region of China. METHODS: Samples from 11,399 hospitalized pediatric patients (≤14 years old), with ARI were tested for HBoV1 and other common respiratory pathogens using real-time PCR, between July 2009 and June 2016. In addition, local meteorological data were collected. RESULTS: Of the 11,399 patients tested, 5606 (49.2%) were positive for at least one respiratory pathogen. Two hundred forty-eight of 11,399 (2.2%) were positive for HBoV1 infection. Co-infection was common in HBoV1-positive patients (45.2%, 112/248). A significant difference in the prevalence of HBoV1 was found in patients in different age groups (p < 0.001), and the peak prevalence was found in patients aged 7–12 months (4.7%, 56/1203). Two HBoV1 prevalence peaks were found in summer (between June and September) and winter (between November and December). The prevalence of HBoV1 was significantly positively correlated with mean temperature and negatively correlated with mean relative humidity, and the mean temperature in the preceding month had better explanatory power than the current monthly temperature. CONCLUSIONS: This study provides a better understanding of the characteristics of HBoV1 infection in children in subtropical regions. Data from this study provide useful information for the future control and prevention of HBoV1 infections.",2018 Jul 16,"['Liu, Wen-Kuan', 'Liu, Qian', 'Chen, De-Hui', 'Tan, Wei-Ping', 'Cai, Yong', 'Qiu, Shu-Yan', 'Xu, Duo', 'Li, Chi', 'Li, Xiao', 'Lin, Zheng-Shi', 'Zhou, Rong']",BMC Infect Dis,,,True
46da38c413e1fc657c3a7ea36435132d38a5e1b4,PMC,Clinical management of respiratory syndrome in patients hospitalized for suspected Middle East respiratory syndrome coronavirus infection in the Paris area from 2013 to 2016,http://dx.doi.org/10.1186/s12879-018-3223-5,PMC6048819,30012113,CC BY,"BACKGROUND: Patients with suspected Middle East respiratory syndrome coronavirus (MERS-CoV) infection should be hospitalized in isolation wards to avoid transmission. This suspicion can also lead to medical confusion and inappropriate management of acute respiratory syndrome due to causes other than MERS-CoV. METHODS: We studied the characteristics and outcome of patients hospitalized for suspected MERS-CoV infection in the isolation wards of two referral infectious disease departments in the Paris area between January 2013 and December 2016. RESULTS: Of 93 adult patients (49 male (52.6%), median age 63.4 years) hospitalized, 82 out of 93 adult patients had returned from Saudi Arabia, and 74 of them were pilgrims (Hajj). Chest X-ray findings were abnormal in 72 (77%) patients. The 93 patients were negative for MERS-CoV RT-PCR, and 70 (75.2%) patients had documented infection, 47 (50.5%) viral, 22 (23.6%) bacterial and one Plasmodium falciparum malaria. Microbiological analysis identified Rhinovirus (27.9%), Influenza virus (26.8%), Legionella pneumophila (7.5%), Streptococcus pneumoniae (7.5%), and non-MERS-coronavirus (6.4%). Antibiotics were initiated in 81 (87%) cases, with two antibiotics in 63 patients (67.7%). The median duration of hospitalization and isolation was 3 days (1–33) and 24 h (8–92), respectively. Time of isolation decreased over time (P < 0.01). Two patients (2%) died. CONCLUSION: The management of patients with possible MERS-CoV infection requires medical facilities with trained personnel, and rapid access to virological results. Empirical treatment with neuraminidase inhibitors and an association of antibiotics effective against S. pneumoniae and L. pneumophila are the cornerstones of the management of patients hospitalized for suspected MERS-CoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3223-5) contains supplementary material, which is available to authorized users.",2018 Jul 16,"['Bleibtreu, A.', 'Jaureguiberry, S.', 'Houhou, N.', 'Boutolleau, D.', 'Guillot, H.', 'Vallois, D.', 'Lucet, J. C.', 'Robert, J.', 'Mourvillier, B.', 'Delemazure, J.', 'Jaspard, M.', 'Lescure, F. X.', 'Rioux, C.', 'Caumes, E.', 'Yazdanapanah, Y.']",BMC Infect Dis,,,True
3b58ee0596ad8476e262079ab15fcfc377e0fec3,PMC,Highlighting Clinical Metagenomics for Enhanced Diagnostic Decision-making: A Step Towards Wider Implementation,http://dx.doi.org/10.1016/j.csbj.2018.02.006,PMC6050174,30026887,CC BY,"Clinical metagenomics (CMg) is the discipline that refers to the sequencing of all nucleic acid material present within a clinical specimen with the intent to recover clinically relevant microbial information. From a diagnostic perspective, next-generation sequencing (NGS) offers the ability to rapidly identify putative pathogens and predict their antimicrobial resistance profiles to optimize targeted treatment regimens. Since the introduction of metagenomics nearly a decade ago, numerous reports have described successful applications in an increasing variety of biological specimens, such as respiratory secretions, cerebrospinal fluid, stool, blood and tissue. Considerable advancements in sequencing and computational technologies in recent years have made CMg a promising tool in clinical microbiology laboratories. Moreover, costs per sample and turnaround time from specimen receipt to clinical management continue to decrease, making the prospect of CMg more feasible. Many difficulties, however, are associated with CMg and warrant further improvements such as the informatics infrastructure and analytical pipelines. Thus, the current review focuses on comprehensively assessing applications of CMg for diagnostic and subtyping purposes.",2018 Feb 27,"['Forbes, Jessica D.', 'Knox, Natalie C.', 'Peterson, Christy-Lynn', 'Reimer, Aleisha R.']",Comput Struct Biotechnol J,,,False
49e38057aa849ee6e304090b6ee1d2633b76f274,PMC,Development of nsP2 protease based cell free high throughput screening assay for evaluation of inhibitors against emerging Chikungunya virus,http://dx.doi.org/10.1038/s41598-018-29024-2,PMC6050329,30018455,CC BY,"Chikungunya virus has emerged as one of the most important global arboviral threats over the last decade. Inspite of large scale morbidity, with long lasting polyarthralgia, so far no licensed vaccine or antiviral is available. CHIKV nsP2 protease is crucial for processing of viral nonstructural polypeptide precursor to release enzymes required for viral replication, thus making it a promising drug target. In this study, high cell density cultivation (HCDC) of Escherichia coli in batch process was carried out to produce rCHIKV nsP2pro in a cost-effective manner. The purified nsP2pro and fluorogenic peptide substrate have been adapted for fluorescence resonance energy transfer (FRET) based high throughput screening (HTS) assay with Z’ value and CV of 0.67 ± 0.054 and <10% respectively. We used this cell free HTS system to screen panel of metal ions and its conjugate which revealed zinc acetate as a potential candidate, which was further found to inhibit CHIKV in Vero cells. Scale-up process has not been previously reported for any of the arboviral nonstructural enzymes. The successful scale-up method for viral protease together with a HTS assay could lead to the development of industrial level large-scale screening platform for identification of protease inhibitors against emerging and re-emerging viruses.",2018 Jul 17,"['Saha, Amrita', 'Acharya, Badri Narayan', 'Priya, Raj', 'Tripathi, Nagesh K.', 'Shrivastava, Ambuj', 'Rao, M. Kameswara', 'Kesari, Pooja', 'Narwal, Manju', 'Tomar, Shailly', 'Bhagyawant, Sameer S.', 'Parida, Manmohan', 'Dash, Paban Kumar']",Sci Rep,,,True
d1f0b5426cd092d2418eebffd0f2146313ac4e11,PMC,Mathematical Analysis of Viral Replication Dynamics and Antiviral Treatment Strategies: From Basic Models to Age-Based Multi-Scale Modeling,http://dx.doi.org/10.3389/fmicb.2018.01546,PMC6050366,30050523,CC BY,"Viral infectious diseases are a global health concern, as is evident by recent outbreaks of the middle east respiratory syndrome, Ebola virus disease, and re-emerging zika, dengue, and chikungunya fevers. Viral epidemics are a socio-economic burden that causes short- and long-term costs for disease diagnosis and treatment as well as a loss in productivity by absenteeism. These outbreaks and their socio-economic costs underline the necessity for a precise analysis of virus-host interactions, which would help to understand disease mechanisms and to develop therapeutic interventions. The combination of quantitative measurements and dynamic mathematical modeling has increased our understanding of the within-host infection dynamics and has led to important insights into viral pathogenesis, transmission, and disease progression. Furthermore, virus-host models helped to identify drug targets, to predict the treatment duration to achieve cure, and to reduce treatment costs. In this article, we review important achievements made by mathematical modeling of viral kinetics on the extracellular, intracellular, and multi-scale level for Human Immunodeficiency Virus, Hepatitis C Virus, Influenza A Virus, Ebola Virus, Dengue Virus, and Zika Virus. Herein, we focus on basic mathematical models on the population scale (so-called target cell-limited models), detailed models regarding the most important steps in the viral life cycle, and the combination of both. For this purpose, we review how mathematical modeling of viral dynamics helped to understand the virus-host interactions and disease progression or clearance. Additionally, we review different types and effects of therapeutic strategies and how mathematical modeling has been used to predict new treatment regimens.",2018 Jul 11,"['Zitzmann, Carolin', 'Kaderali, Lars']",Front Microbiol,,,True
29fdfade9c2f2ec46e06085777de897e0a613984,PMC,Analysis of codon usage patterns in Hirudinaria manillensis reveals a preference for GC-ending codons caused by dominant selection constraints,http://dx.doi.org/10.1186/s12864-018-4937-x,PMC6050667,30016953,CC BY,"BACKGROUND: Hirudinaria manillensis is an ephemeral, blood-sucking ectoparasite, possessing anticoagulant capacities with potential medical applications. Analysis of codon usage patterns would contribute to our understanding of the evolutionary mechanisms and genetic architecture of H. manillensis, which in turn would provide insight into the characteristics of other leeches. We analysed codon usage and related indices using 18,000 coding sequences (CDSs) retrieved from H. manillensis RNA-Seq data. RESULTS: We identified four highly preferred codons in H. manillensis that have G/C-endings. Points generated in an effective number of codons (ENC) plot distributed below the standard curve and the slope of a neutrality plot was less than 1. Highly expressed CDSs had lower ENC content and higher GC content than weakly expressed CDSs. Principal component analysis conducted on relative synonymous codon usage (RSCU) values divided CDSs according to GC content and divided codons according to ending bases. Moreover, by determining codon usage, we found that the majority of blood-diet related genes have undergone less adaptive evolution in H. manillensis, except for those with homologous sequences in the host species. CONCLUSIONS: Codon usage in H. manillensis had an overall preference toward C-endings and indicated that codon usage patterns are mediated by differential expression, GC content, and biological function. Although mutation pressure effects were also notable, the majority of genetic evolution in H. manillensis was driven by natural selection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-4937-x) contains supplementary material, which is available to authorized users.",2018 Jul 17,"['Guan, De-Long', 'Ma, Li-Bin', 'Khan, Muhammad Salabat', 'Zhang, Xiu-Xiu', 'Xu, Sheng-Quan', 'Xie, Juan-Ying']",BMC Genomics,,,True
fd95b5ef9a8a47db9d250259365c425206d4dd4c,PMC,High-resolution epidemic simulation using within-host infection and contact data,http://dx.doi.org/10.1186/s12889-018-5709-x,PMC6050668,30016958,CC BY,"BACKGROUND: Recent epidemics have entailed global discussions on revamping epidemic control and prevention approaches. A general consensus is that all sources of data should be embraced to improve epidemic preparedness. As a disease transmission is inherently governed by individual-level responses, pathogen dynamics within infected hosts posit high potentials to inform population-level phenomena. We propose a multiscale approach showing that individual dynamics were able to reproduce population-level observations. METHODS: Using experimental data, we formulated mathematical models of pathogen infection dynamics from which we simulated mechanistically its transmission parameters. The models were then embedded in our implementation of an age-specific contact network that allows to express individual differences relevant to the transmission processes. This approach is illustrated with an example of Ebola virus (EBOV). RESULTS: The results showed that a within-host infection model can reproduce EBOV’s transmission parameters obtained from population data. At the same time, population age-structure, contact distribution and patterns can be expressed using network generating algorithm. This framework opens a vast opportunity to investigate individual roles of factors involved in the epidemic processes. Estimating EBOV’s reproduction number revealed a heterogeneous pattern among age-groups, prompting cautions on estimates unadjusted for contact pattern. Assessments of mass vaccination strategies showed that vaccination conducted in a time window from five months before to one week after the start of an epidemic appeared to strongly reduce epidemic size. Noticeably, compared to a non-intervention scenario, a low critical vaccination coverage of 33% cannot ensure epidemic extinction but could reduce the number of cases by ten to hundred times as well as lessen the case-fatality rate. CONCLUSIONS: Experimental data on the within-host infection have been able to capture upfront key transmission parameters of a pathogen; the applications of this approach will give us more time to prepare for potential epidemics. The population of interest in epidemic assessments could be modelled with an age-specific contact network without exhaustive amount of data. Further assessments and adaptations for different pathogens and scenarios to explore multilevel aspects in infectious diseases epidemics are underway. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-018-5709-x) contains supplementary material, which is available to authorized users.",2018 Jul 17,"['Nguyen, Van Kinh', 'Mikolajczyk, Rafael', 'Hernandez-Vargas, Esteban Abelardo']",BMC Public Health,,,False
ba5afd4400ce9d4af20bc2ae6a1742add59b7161,PMC,High-resolution epidemic simulation using within-host infection and contact data,http://dx.doi.org/10.1186/s12889-018-5709-x,PMC6050668,30016958,CC BY,"BACKGROUND: Recent epidemics have entailed global discussions on revamping epidemic control and prevention approaches. A general consensus is that all sources of data should be embraced to improve epidemic preparedness. As a disease transmission is inherently governed by individual-level responses, pathogen dynamics within infected hosts posit high potentials to inform population-level phenomena. We propose a multiscale approach showing that individual dynamics were able to reproduce population-level observations. METHODS: Using experimental data, we formulated mathematical models of pathogen infection dynamics from which we simulated mechanistically its transmission parameters. The models were then embedded in our implementation of an age-specific contact network that allows to express individual differences relevant to the transmission processes. This approach is illustrated with an example of Ebola virus (EBOV). RESULTS: The results showed that a within-host infection model can reproduce EBOV’s transmission parameters obtained from population data. At the same time, population age-structure, contact distribution and patterns can be expressed using network generating algorithm. This framework opens a vast opportunity to investigate individual roles of factors involved in the epidemic processes. Estimating EBOV’s reproduction number revealed a heterogeneous pattern among age-groups, prompting cautions on estimates unadjusted for contact pattern. Assessments of mass vaccination strategies showed that vaccination conducted in a time window from five months before to one week after the start of an epidemic appeared to strongly reduce epidemic size. Noticeably, compared to a non-intervention scenario, a low critical vaccination coverage of 33% cannot ensure epidemic extinction but could reduce the number of cases by ten to hundred times as well as lessen the case-fatality rate. CONCLUSIONS: Experimental data on the within-host infection have been able to capture upfront key transmission parameters of a pathogen; the applications of this approach will give us more time to prepare for potential epidemics. The population of interest in epidemic assessments could be modelled with an age-specific contact network without exhaustive amount of data. Further assessments and adaptations for different pathogens and scenarios to explore multilevel aspects in infectious diseases epidemics are underway. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-018-5709-x) contains supplementary material, which is available to authorized users.",2018 Jul 17,"['Nguyen, Van Kinh', 'Mikolajczyk, Rafael', 'Hernandez-Vargas, Esteban Abelardo']",BMC Public Health,,,False
a4860aeadf8a51f4702262a58b808ea851eb4c27,PMC,High-resolution epidemic simulation using within-host infection and contact data,http://dx.doi.org/10.1186/s12889-018-5709-x,PMC6050668,30016958,CC BY,"BACKGROUND: Recent epidemics have entailed global discussions on revamping epidemic control and prevention approaches. A general consensus is that all sources of data should be embraced to improve epidemic preparedness. As a disease transmission is inherently governed by individual-level responses, pathogen dynamics within infected hosts posit high potentials to inform population-level phenomena. We propose a multiscale approach showing that individual dynamics were able to reproduce population-level observations. METHODS: Using experimental data, we formulated mathematical models of pathogen infection dynamics from which we simulated mechanistically its transmission parameters. The models were then embedded in our implementation of an age-specific contact network that allows to express individual differences relevant to the transmission processes. This approach is illustrated with an example of Ebola virus (EBOV). RESULTS: The results showed that a within-host infection model can reproduce EBOV’s transmission parameters obtained from population data. At the same time, population age-structure, contact distribution and patterns can be expressed using network generating algorithm. This framework opens a vast opportunity to investigate individual roles of factors involved in the epidemic processes. Estimating EBOV’s reproduction number revealed a heterogeneous pattern among age-groups, prompting cautions on estimates unadjusted for contact pattern. Assessments of mass vaccination strategies showed that vaccination conducted in a time window from five months before to one week after the start of an epidemic appeared to strongly reduce epidemic size. Noticeably, compared to a non-intervention scenario, a low critical vaccination coverage of 33% cannot ensure epidemic extinction but could reduce the number of cases by ten to hundred times as well as lessen the case-fatality rate. CONCLUSIONS: Experimental data on the within-host infection have been able to capture upfront key transmission parameters of a pathogen; the applications of this approach will give us more time to prepare for potential epidemics. The population of interest in epidemic assessments could be modelled with an age-specific contact network without exhaustive amount of data. Further assessments and adaptations for different pathogens and scenarios to explore multilevel aspects in infectious diseases epidemics are underway. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-018-5709-x) contains supplementary material, which is available to authorized users.",2018 Jul 17,"['Nguyen, Van Kinh', 'Mikolajczyk, Rafael', 'Hernandez-Vargas, Esteban Abelardo']",BMC Public Health,,,True
84e3663e6544caf4cac64a937e7e3f6159717c3c,PMC,Moving Forward: Recent Developments for the Ferret Biomedical Research Model,http://dx.doi.org/10.1128/mBio.01113-18,PMC6050969,30018107,CC BY,"Since the initial report in 1911, the domestic ferret has become an invaluable biomedical research model. While widely recognized for its utility in influenza virus research, ferrets are used for a variety of infectious and noninfectious disease models due to the anatomical, metabolic, and physiological features they share with humans and their susceptibility to many human pathogens. However, there are limitations to the model that must be overcome for maximal utility for the scientific community. Here, we describe important recent advances that will accelerate biomedical research with this animal model.",2018 Jul 17,"['Albrecht, Randy A.', 'Liu, Wen-Chun', 'Sant, Andrea J.', 'Tompkins, S. Mark', 'Pekosz, Andrew', 'Meliopoulos, Victoria', 'Cherry, Sean', 'Thomas, Paul G.', 'Schultz-Cherry, Stacey']",mBio,,,True
4c6fefd5a9ce1f7df6a863b7d91410d03bfc9139,PMC,Feline calicivirus- and murine norovirus-induced COX-2/PGE(2) signaling pathway has proviral effects,http://dx.doi.org/10.1371/journal.pone.0200726,PMC6051663,30021004,CC BY,"Cyclooxygenases (COXs)/prostaglandin E(2) (PGE(2)) signaling pathways are known to modulate a variety of homeostatic processes and are involved in various pathophysiological conditions. COXs/PGE(2) signaling pathways have also been demonstrated to have proviral or antiviral effects, which appeared different even in the same virus family. A porcine sapovirus Cowden strain, a member of genus Sapovirus within the Caliciviridae family, induces strong COX-2/PGE(2) but transient COX-1/PGE(2) signaling to enhance virus replication. However, whether infections of other viruses in the different genera activate COXs/PGE(2) signaling, and thus affect the replication of viruses, remains unknown. In the present study, infections of cells with the feline calicivirus (FCV) F9 strain in the genus Vesivirus and murine norovirus (MNV) CW-1 strain in the genus Norovirus only activated the COX-2/PGE(2) signaling in a time-dependent manner. Treatment with pharmacological inhibitors or transfection of small interfering RNAs (siRNAs) against COX-2 enzyme significantly reduced the production of PGE(2) as well as FCV and MNV replications. The inhibitory effects of these pharmacological inhibitors against COX-2 enzyme on the replication of both viruses were restored by the addition of PGE(2). Silencing of COX-1 via siRNAs and inhibition of COX-1 via an inhibitor also decrease the production of PGE(2) and replication of both viruses, which can be attributed to the inhibition COX-1/PGE(2) signaling pathway. These data indicate that the COX-2/PGE(2) signaling pathway has proviral effects for the replication of FCV and MNV, and pharmacological inhibitors against these enzymes serve as potential therapeutic candidates for treating FCV and MNV infections.",2018 Jul 18,"['Alfajaro, Mia Madel', 'Cho, Eun-Hyo', 'Park, Jun-Gyu', 'Kim, Ji-Yun', 'Soliman, Mahmoud', 'Baek, Yeong-Bin', 'Kang, Mun-Il', 'Park, Sang-Ik', 'Cho, Kyoung-Oh']",PLoS One,,,True
88f92fbe9b0ef301ed99a0f84c88beca964fad97,PMC,Cross-Species Meta-Analysis of Transcriptomic Data in Combination With Supervised Machine Learning Models Identifies the Common Gene Signature of Lactation Process,http://dx.doi.org/10.3389/fgene.2018.00235,PMC6052129,30050559,CC BY,"Lactation, a physiologically complex process, takes place in mammary gland after parturition. The expression profile of the effective genes in lactation has not comprehensively been elucidated. Herein, meta-analysis, using publicly available microarray data, was conducted identify the differentially expressed genes (DEGs) between pre- and post-peak milk production. Three microarray datasets of Rat, Bos Taurus, and Tammar wallaby were used. Samples related to pre-peak (n = 85) and post-peak (n = 24) milk production were selected. Meta-analysis revealed 31 DEGs across the studied species. Interestingly, 10 genes, including MRPS18B, SF1, UQCRC1, NUCB1, RNF126, ADSL, TNNC1, FIS1, HES5 and THTPA, were not detected in original studies that highlights meta-analysis power in biosignature discovery. Common target and regulator analysis highlighted the high connectivity of CTNNB1, CDD4 and LPL as gene network hubs. As data originally came from three different species, to check the effects of heterogeneous data sources on DEGs, 10 attribute weighting (machine learning) algorithms were applied. Attribute weighting results showed that the type of organism had no or little effect on the selected gene list. Systems biology analysis suggested that these DEGs affect the milk production by improving the immune system performance and mammary cell growth. This is the first study employing both meta-analysis and machine learning approaches for comparative analysis of gene expression pattern of mammary glands in two important time points of lactation process. The finding may pave the way to use of publically available to elucidate the underlying molecular mechanisms of physiologically complex traits such as lactation in mammals.",2018 Jul 12,"['Farhadian, Mohammad', 'Rafat, Seyed A.', 'Hasanpur, Karim', 'Ebrahimi, Mansour', 'Ebrahimie, Esmaeil']",Front Genet,,,True
911e313c1ff9ff3edb62e71b7aea6224f771fadd,PMC,Air-Liquid Interface Method To Study Epstein-Barr Virus Pathogenesis in Nasopharyngeal Epithelial Cells,http://dx.doi.org/10.1128/mSphere.00152-18,PMC6052337,30021875,CC BY,"Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that establishes a latent reservoir in peripheral B-lymphocytes with sporadic reactivation. EBV also infects epithelial cells, predominantly resulting in a lytic infection, which may contribute to EBV transmission from saliva. In the nasopharynx, EBV infection can lead to the clonal expansion of a latently infected cell and the development of nasopharyngeal carcinoma (NPC). The mechanisms governing EBV pathogenesis in nasopharyngeal epithelium are largely unknown. An advanced understanding would depend on a physiologically relevant culture model of polarized airway epithelium. The recent application of the organotypic raft culture in keratinocytes has demonstrated great promise for the use of polarized cultures in the study of EBV permissive replication. In this study, the adaptation of an air-liquid interface (ALI) culture method using transwell membranes was explored in an EBV-infected NPC cell line. In the EBV-infected NPC HK1 cell line, ALI culture resulted in the completion of EBV reactivation, with global induction of the lytic cascade, replication of EBV genomes, and production of infectious progeny virus. We propose that the ALI culture method can be widely adopted as a physiologically relevant model to study EBV pathogenesis in polarized nasal epithelial cells. IMPORTANCE Lifting adherent cells to the air-liquid interface (ALI) is a method conventionally used to culture airway epithelial cells into polarized apical and basolateral surfaces. Reactivation of Epstein-Barr virus (EBV) from monolayer epithelial cultures is sometimes abortive, which may be attributed to the lack of authentic reactivation triggers that occur in stratified epithelium in vivo. In the present work, the ALI culture method was applied to study EBV reactivation in nasopharyngeal epithelial cells. The ALI culture of an EBV-infected cell line yielded high titers and can be dissected by a variety of molecular virology assays that measure induction of the EBV lytic cascade and EBV genome replication and assembly. EBV infection of polarized cultures of primary epithelial cells can be challenging and can have variable efficiencies. However, the use of the ALI method with established EBV-infected cell lines offers a readily available and reproducible approach for the study of EBV permissive replication in polarized epithelia.",2018 Jul 18,"['Caves, Elizabeth A.', 'Cook, Sarah A.', 'Lee, Nara', 'Stoltz, Donna', 'Watkins, Simon', 'Shair, Kathy H. Y.']",mSphere,,,True
c819bee642ae0f97b4d9e85a8558ccc1537dab2f,PMC,"Bacterial diversity of bat guano from Cabalyorisa Cave, Mabini, Pangasinan, Philippines: A first report on the metagenome of Philippine bat guano",http://dx.doi.org/10.1371/journal.pone.0200095,PMC6053158,30024917,CC BY,"Bats are highly diverse and ecologically valuable mammals. They serve as host to bacteria, viruses and fungi that are either beneficial or harmful to its colony as well as to other groups of cave organisms. The bacterial diversity of two bat guano samples, C1 and C2, from Cabalyorisa Cave, Mabini, Pangasinan, Philippines were investigated using 16S rRNA gene amplicon sequencing. V3-V4 hypervariable regions were amplified and then sequenced using Illumina MiSeq 250 PE system. Reads were processed using Mothur and QIIME pipelines and assigned 12,345 OTUs for C1 and 5,408 OTUs for C2. The most dominant OTUs in C1 belong to the Proteobacteria (61.7%), Actinobacteria (19.4%), Bacteroidetes (4.2%), Firmicutes (2.7%), Chloroflexi (2.5%), candidate phylum TM7 (2.3%) and Planctomycetes (1.9%) while Proteobacteria (61.7%) and Actinobacteria (34.9%) dominated C2. Large proportion of sequence reads mainly associated with unclassified bacteria indicated possible occurrence of novel bacteria in both samples. XRF spectrophotometric analyses of C1 and C2 guano revealed significant differences in the composition of both major and trace elements. C1 guano recorded high levels of Si, Fe, Mg, Al, Mn, Ti and Cu while C2 samples registered high concentrations of Ca, P, S, Zn and Cr. Community structure of the samples were compared with other published community profiling studies from Finland (SRR868695), Meghalaya, Northeast India (SRR1793374) and Maharashtra State, India (CGS). Core microbiome among samples were determined for comparison. Variations were observed among previously studied guano samples and the Cabalyorisa Cave samples were attributed to either bat sources or age of the guano. This is the first study on bacterial diversity of guano in the Philippines through high-throughput sequencing.",2018 Jul 19,"['P. De Leon, Marian', 'Montecillo, Andrew D.', 'Pinili, Dale S.', 'Siringan, Maria Auxilia T.', 'Park, Doo-Sang']",PLoS One,,,True
ddba9808c2e5a41e0a27996ff5b59e4c09ae159a,PMC,Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB,http://dx.doi.org/10.1371/journal.ppat.1007111,PMC6053247,30024968,CC BY,"Hepatitis C virus (HCV) and the malaria parasite Plasmodium use the membrane protein CD81 to invade human liver cells. Here we mapped 33 host protein interactions of CD81 in primary human liver and hepatoma cells using high-resolution quantitative proteomics. In the CD81 protein network, we identified five proteins which are HCV entry factors or facilitators including epidermal growth factor receptor (EGFR). Notably, we discovered calpain-5 (CAPN5) and the ubiquitin ligase Casitas B-lineage lymphoma proto-oncogene B (CBLB) to form a complex with CD81 and support HCV entry. CAPN5 and CBLB were required for a post-binding and pre-replication step in the HCV life cycle. Knockout of CAPN5 and CBLB reduced susceptibility to all tested HCV genotypes, but not to other enveloped viruses such as vesicular stomatitis virus and human coronavirus. Furthermore, Plasmodium sporozoites relied on a distinct set of CD81 interaction partners for liver cell entry. Our findings reveal a comprehensive CD81 network in human liver cells and show that HCV and Plasmodium highjack selective CD81 interactions, including CAPN5 and CBLB for HCV, to invade cells.",2018 Jul 19,"['Bruening, Janina', 'Lasswitz, Lisa', 'Banse, Pia', 'Kahl, Sina', 'Marinach, Carine', 'Vondran, Florian W.', 'Kaderali, Lars', 'Silvie, Olivier', 'Pietschmann, Thomas', 'Meissner, Felix', 'Gerold, Gisa']",PLoS Pathog,,,True
c3d210df12dab3dfa4d9a51c0d0a722a667aa262,PMC,A novel European H5N8 influenza A virus has increased virulence in ducks but low zoonotic potential,http://dx.doi.org/10.1038/s41426-018-0130-1,PMC6053424,30026505,CC BY,"We investigated in a unique setup of animal models and a human lung explant culture biological properties, including zoonotic potential, of a representative 2016 highly pathogenic avian influenza virus (HPAIV) H5N8, clade 2.3.4.4 group B (H5N8B), that spread rapidly in a huge and ongoing outbreak series in Europe and caused high mortality in waterfowl and domestic birds. HPAIV H5N8B showed increased virulence with rapid onset of severe disease and mortality in Pekin ducks due to pronounced neuro- and hepatotropism. Cross-species infection was evaluated in mice, ferrets, and in a human lung explant culture model. While the H5N8B isolate was highly virulent for Balb/c mice, virulence and transmissibility were grossly reduced in ferrets, which was mirrored by marginal replication in human lung cultures infected ex vivo. Our data indicate that the 2016 HPAIV H5N8B is avian-adapted with augmented virulence for waterfowl, but has low zoonotic potential. The here tested combination of animal studies with the inoculation of human explants provides a promising future workflow to evaluate zoonotic potential, mammalian replication competence and avian virulence of HPAIV.",2018 Jul 19,"['Grund, Christian', 'Hoffmann, Donata', 'Ulrich, Reiner', 'Naguib, Mahmoud', 'Schinköthe, Jan', 'Hoffmann, Bernd', 'Harder, Timm', 'Saenger, Sandra', 'Zscheppang, Katja', 'Tönnies, Mario', 'Hippenstiel, Stefan', 'Hocke, Andreas', 'Wolff, Thorsten', 'Beer, Martin']",Emerg Microbes Infect,,,True
deaac80fa1b6ee6b493932b297496c8751c9ef1b,PMC,A novel European H5N8 influenza A virus has increased virulence in ducks but low zoonotic potential,http://dx.doi.org/10.1038/s41426-018-0130-1,PMC6053424,30026505,CC BY,"We investigated in a unique setup of animal models and a human lung explant culture biological properties, including zoonotic potential, of a representative 2016 highly pathogenic avian influenza virus (HPAIV) H5N8, clade 2.3.4.4 group B (H5N8B), that spread rapidly in a huge and ongoing outbreak series in Europe and caused high mortality in waterfowl and domestic birds. HPAIV H5N8B showed increased virulence with rapid onset of severe disease and mortality in Pekin ducks due to pronounced neuro- and hepatotropism. Cross-species infection was evaluated in mice, ferrets, and in a human lung explant culture model. While the H5N8B isolate was highly virulent for Balb/c mice, virulence and transmissibility were grossly reduced in ferrets, which was mirrored by marginal replication in human lung cultures infected ex vivo. Our data indicate that the 2016 HPAIV H5N8B is avian-adapted with augmented virulence for waterfowl, but has low zoonotic potential. The here tested combination of animal studies with the inoculation of human explants provides a promising future workflow to evaluate zoonotic potential, mammalian replication competence and avian virulence of HPAIV.",2018 Jul 19,"['Grund, Christian', 'Hoffmann, Donata', 'Ulrich, Reiner', 'Naguib, Mahmoud', 'Schinköthe, Jan', 'Hoffmann, Bernd', 'Harder, Timm', 'Saenger, Sandra', 'Zscheppang, Katja', 'Tönnies, Mario', 'Hippenstiel, Stefan', 'Hocke, Andreas', 'Wolff, Thorsten', 'Beer, Martin']",Emerg Microbes Infect,,,True
f437e7708a092a65e1bf20065dfdfb2e17546825,PMC,Detection of human bocavirus-1 in both nasal and stool specimens from children under 5 years old with influenza-like illnesses or diarrhea in Gabon,http://dx.doi.org/10.1186/s13104-018-3605-1,PMC6053798,30029615,CC BY,"OBJECTIVE: Human bocavirus (HBoV) is a viral pathogen which causes respiratory tract diseases and acute gastroenteritis worldwide. This virus mainly affected children under 5 years old. There is little information on HBoV in Gabon. Two first studies was conducted to determine the prevalence of respiratory and enteric viruses in children under 5 years old who visited health centers for influenza-like illness (ILI) or diarrhea in Gabon from March 2010 to June 2011. However, HBoV was not included in the screening. The aim of this retrospective study was to evaluate the prevalence and the HBoV genotype in children under 5 years old with ILI or diarrhea in Gabon. RESULTS: A total of 810 nasal swabs and 317 feces samples collected during the two first study were analyzed among which 32 (4.4%) and 7 (2.2%) were positive for HBoV respectively. While there were no significant differences in prevalence between age groups in children with ILI, all children with diarrhea were under 12 months of age. Moreover, 84.4 and 42.8% were diagnosed in co-infections with at least one other respiratory virus, or enteric viruses respectively. Finally, HBoV subtype 1 has been detected in both respiratory and gastrointestinal tracts with very low variability.",2018 Jul 20,"['Lekana-Douki, Sonia Etenna', 'Behillil, Sylvie', 'Enouf, Vincent', 'Leroy, Eric M.', 'Berthet, Nicolas']",BMC Res Notes,,,True
540f31cf68c580d6d3bf7f4bfd89e10767b89030,PMC,De novo design of isopeptide bond-tethered triple-stranded coiled coils with exceptional resistance to unfolding and proteolysis: implication for developing antiviral therapeutics,http://dx.doi.org/10.1039/c5sc02220g,PMC6054081,30090269,CC BY,"Isopeptide bond-tethered triple-stranded coiled coils of HIV-1 gp41 N-terminal heptad repeat (NHR) peptides have been designed with de novo auxiliaries to guide site-directed trimerized cross-linking. The presence of isopeptide bridges in the rationally designed trimerization motifs provides extraordinary stability to withstand thermal and chemical denaturation. As a result, these ultra-stable and well-folded trimeric coiled coils direct and yield proteolysis-resistant and remarkably potent N-peptide chimeric trimers with HIV-1 fusion inhibitory activities in the low nanomolar range, much more effective than the corresponding unstructured N-peptide monomers and reaching the potency of clinically used T20 peptide (enfuvirtide). Thus, these isopeptide bond-crosslinked de novo coiled coils may also be used as attractive scaffolds for isolating NHR-trimers in other class I enveloped viruses for therapeutic intervention. Furthermore, this isopeptide bridge-tethering strategy could be extendable to the construction of ultra-stable proteins interfering with certain biological processes.",2015 Nov 1,"['Wang, Chao', 'Lai, Wenqing', 'Yu, Fei', 'Zhang, Tianhong', 'Lu, Lu', 'Jiang, Xifeng', 'Zhang, Zhenqing', 'Xu, Xiaoyu', 'Bai, Yu', 'Jiang, Shibo', 'Liu, Keliang']",Chem Sci,,,True
552afd4d303ff6838e7ae4ac55569b25056374ab,PMC,De novo design of isopeptide bond-tethered triple-stranded coiled coils with exceptional resistance to unfolding and proteolysis: implication for developing antiviral therapeutics,http://dx.doi.org/10.1039/c5sc02220g,PMC6054081,30090269,CC BY,"Isopeptide bond-tethered triple-stranded coiled coils of HIV-1 gp41 N-terminal heptad repeat (NHR) peptides have been designed with de novo auxiliaries to guide site-directed trimerized cross-linking. The presence of isopeptide bridges in the rationally designed trimerization motifs provides extraordinary stability to withstand thermal and chemical denaturation. As a result, these ultra-stable and well-folded trimeric coiled coils direct and yield proteolysis-resistant and remarkably potent N-peptide chimeric trimers with HIV-1 fusion inhibitory activities in the low nanomolar range, much more effective than the corresponding unstructured N-peptide monomers and reaching the potency of clinically used T20 peptide (enfuvirtide). Thus, these isopeptide bond-crosslinked de novo coiled coils may also be used as attractive scaffolds for isolating NHR-trimers in other class I enveloped viruses for therapeutic intervention. Furthermore, this isopeptide bridge-tethering strategy could be extendable to the construction of ultra-stable proteins interfering with certain biological processes.",2015 Nov 1,"['Wang, Chao', 'Lai, Wenqing', 'Yu, Fei', 'Zhang, Tianhong', 'Lu, Lu', 'Jiang, Xifeng', 'Zhang, Zhenqing', 'Xu, Xiaoyu', 'Bai, Yu', 'Jiang, Shibo', 'Liu, Keliang']",Chem Sci,,,False
08beca0f49f6c33cf0ea4544f6dfe34b5932214d,PMC,Automated Real-Time Collection of Pathogen-Specific Diagnostic Data: Syndromic Infectious Disease Epidemiology,http://dx.doi.org/10.2196/publichealth.9876,PMC6054708,29980501,CC BY,"BACKGROUND: Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. OBJECTIVE: The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems. METHODS: We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States. RESULTS: The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present. CONCLUSIONS: Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks.",2018 Jul 6,"['Meyers, Lindsay', 'Ginocchio, Christine C', 'Faucett, Aimie N', 'Nolte, Frederick S', 'Gesteland, Per H', 'Leber, Amy', 'Janowiak, Diane', 'Donovan, Virginia', 'Dien Bard, Jennifer', 'Spitzer, Silvia', 'Stellrecht, Kathleen A', 'Salimnia, Hossein', 'Selvarangan, Rangaraj', 'Juretschko, Stefan', 'Daly, Judy A', 'Wallentine, Jeremy C', 'Lindsey, Kristy', 'Moore, Franklin', 'Reed, Sharon L', 'Aguero-Rosenfeld, Maria', 'Fey, Paul D', 'Storch, Gregory A', 'Melnick, Steve J', 'Robinson, Christine C', 'Meredith, Jennifer F', 'Cook, Camille V', 'Nelson, Robert K', 'Jones, Jay D', 'Scarpino, Samuel V', 'Althouse, Benjamin M', 'Ririe, Kirk M', 'Malin, Bradley A', 'Poritz, Mark A']",JMIR Public Health Surveill,,,True
5ca68ac4cbda643bc9b11a04d5fdb30cd57b3c4d,PMC,Automated Real-Time Collection of Pathogen-Specific Diagnostic Data: Syndromic Infectious Disease Epidemiology,http://dx.doi.org/10.2196/publichealth.9876,PMC6054708,29980501,CC BY,"BACKGROUND: Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. OBJECTIVE: The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems. METHODS: We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States. RESULTS: The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present. CONCLUSIONS: Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks.",2018 Jul 6,"['Meyers, Lindsay', 'Ginocchio, Christine C', 'Faucett, Aimie N', 'Nolte, Frederick S', 'Gesteland, Per H', 'Leber, Amy', 'Janowiak, Diane', 'Donovan, Virginia', 'Dien Bard, Jennifer', 'Spitzer, Silvia', 'Stellrecht, Kathleen A', 'Salimnia, Hossein', 'Selvarangan, Rangaraj', 'Juretschko, Stefan', 'Daly, Judy A', 'Wallentine, Jeremy C', 'Lindsey, Kristy', 'Moore, Franklin', 'Reed, Sharon L', 'Aguero-Rosenfeld, Maria', 'Fey, Paul D', 'Storch, Gregory A', 'Melnick, Steve J', 'Robinson, Christine C', 'Meredith, Jennifer F', 'Cook, Camille V', 'Nelson, Robert K', 'Jones, Jay D', 'Scarpino, Samuel V', 'Althouse, Benjamin M', 'Ririe, Kirk M', 'Malin, Bradley A', 'Poritz, Mark A']",JMIR Public Health Surveill,,,True
630c109d58e4c5dcf3bb135d25c57cf2f20ec032,PMC,Automated Real-Time Collection of Pathogen-Specific Diagnostic Data: Syndromic Infectious Disease Epidemiology,http://dx.doi.org/10.2196/publichealth.9876,PMC6054708,29980501,CC BY,"BACKGROUND: Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. OBJECTIVE: The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems. METHODS: We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States. RESULTS: The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present. CONCLUSIONS: Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks.",2018 Jul 6,"['Meyers, Lindsay', 'Ginocchio, Christine C', 'Faucett, Aimie N', 'Nolte, Frederick S', 'Gesteland, Per H', 'Leber, Amy', 'Janowiak, Diane', 'Donovan, Virginia', 'Dien Bard, Jennifer', 'Spitzer, Silvia', 'Stellrecht, Kathleen A', 'Salimnia, Hossein', 'Selvarangan, Rangaraj', 'Juretschko, Stefan', 'Daly, Judy A', 'Wallentine, Jeremy C', 'Lindsey, Kristy', 'Moore, Franklin', 'Reed, Sharon L', 'Aguero-Rosenfeld, Maria', 'Fey, Paul D', 'Storch, Gregory A', 'Melnick, Steve J', 'Robinson, Christine C', 'Meredith, Jennifer F', 'Cook, Camille V', 'Nelson, Robert K', 'Jones, Jay D', 'Scarpino, Samuel V', 'Althouse, Benjamin M', 'Ririe, Kirk M', 'Malin, Bradley A', 'Poritz, Mark A']",JMIR Public Health Surveill,,,False
1641c3f3935d9db32f0ae54c3e1ab494016d2416,PMC,Automated Real-Time Collection of Pathogen-Specific Diagnostic Data: Syndromic Infectious Disease Epidemiology,http://dx.doi.org/10.2196/publichealth.9876,PMC6054708,29980501,CC BY,"BACKGROUND: Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. OBJECTIVE: The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems. METHODS: We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States. RESULTS: The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present. CONCLUSIONS: Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks.",2018 Jul 6,"['Meyers, Lindsay', 'Ginocchio, Christine C', 'Faucett, Aimie N', 'Nolte, Frederick S', 'Gesteland, Per H', 'Leber, Amy', 'Janowiak, Diane', 'Donovan, Virginia', 'Dien Bard, Jennifer', 'Spitzer, Silvia', 'Stellrecht, Kathleen A', 'Salimnia, Hossein', 'Selvarangan, Rangaraj', 'Juretschko, Stefan', 'Daly, Judy A', 'Wallentine, Jeremy C', 'Lindsey, Kristy', 'Moore, Franklin', 'Reed, Sharon L', 'Aguero-Rosenfeld, Maria', 'Fey, Paul D', 'Storch, Gregory A', 'Melnick, Steve J', 'Robinson, Christine C', 'Meredith, Jennifer F', 'Cook, Camille V', 'Nelson, Robert K', 'Jones, Jay D', 'Scarpino, Samuel V', 'Althouse, Benjamin M', 'Ririe, Kirk M', 'Malin, Bradley A', 'Poritz, Mark A']",JMIR Public Health Surveill,,,False
414942226e630a7c4e040ee9a09230d15d58565a,PMC,Automated Real-Time Collection of Pathogen-Specific Diagnostic Data: Syndromic Infectious Disease Epidemiology,http://dx.doi.org/10.2196/publichealth.9876,PMC6054708,29980501,CC BY,"BACKGROUND: Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. OBJECTIVE: The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems. METHODS: We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States. RESULTS: The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present. CONCLUSIONS: Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks.",2018 Jul 6,"['Meyers, Lindsay', 'Ginocchio, Christine C', 'Faucett, Aimie N', 'Nolte, Frederick S', 'Gesteland, Per H', 'Leber, Amy', 'Janowiak, Diane', 'Donovan, Virginia', 'Dien Bard, Jennifer', 'Spitzer, Silvia', 'Stellrecht, Kathleen A', 'Salimnia, Hossein', 'Selvarangan, Rangaraj', 'Juretschko, Stefan', 'Daly, Judy A', 'Wallentine, Jeremy C', 'Lindsey, Kristy', 'Moore, Franklin', 'Reed, Sharon L', 'Aguero-Rosenfeld, Maria', 'Fey, Paul D', 'Storch, Gregory A', 'Melnick, Steve J', 'Robinson, Christine C', 'Meredith, Jennifer F', 'Cook, Camille V', 'Nelson, Robert K', 'Jones, Jay D', 'Scarpino, Samuel V', 'Althouse, Benjamin M', 'Ririe, Kirk M', 'Malin, Bradley A', 'Poritz, Mark A']",JMIR Public Health Surveill,,,False
b52a42113ba68d51829ee0290195bba734466d24,PMC,Automated Real-Time Collection of Pathogen-Specific Diagnostic Data: Syndromic Infectious Disease Epidemiology,http://dx.doi.org/10.2196/publichealth.9876,PMC6054708,29980501,CC BY,"BACKGROUND: Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. OBJECTIVE: The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems. METHODS: We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States. RESULTS: The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present. CONCLUSIONS: Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks.",2018 Jul 6,"['Meyers, Lindsay', 'Ginocchio, Christine C', 'Faucett, Aimie N', 'Nolte, Frederick S', 'Gesteland, Per H', 'Leber, Amy', 'Janowiak, Diane', 'Donovan, Virginia', 'Dien Bard, Jennifer', 'Spitzer, Silvia', 'Stellrecht, Kathleen A', 'Salimnia, Hossein', 'Selvarangan, Rangaraj', 'Juretschko, Stefan', 'Daly, Judy A', 'Wallentine, Jeremy C', 'Lindsey, Kristy', 'Moore, Franklin', 'Reed, Sharon L', 'Aguero-Rosenfeld, Maria', 'Fey, Paul D', 'Storch, Gregory A', 'Melnick, Steve J', 'Robinson, Christine C', 'Meredith, Jennifer F', 'Cook, Camille V', 'Nelson, Robert K', 'Jones, Jay D', 'Scarpino, Samuel V', 'Althouse, Benjamin M', 'Ririe, Kirk M', 'Malin, Bradley A', 'Poritz, Mark A']",JMIR Public Health Surveill,,,False
a7864f469a8f8255009183571481a1424b78e759,PMC,Automated Real-Time Collection of Pathogen-Specific Diagnostic Data: Syndromic Infectious Disease Epidemiology,http://dx.doi.org/10.2196/publichealth.9876,PMC6054708,29980501,CC BY,"BACKGROUND: Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. OBJECTIVE: The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems. METHODS: We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States. RESULTS: The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present. CONCLUSIONS: Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks.",2018 Jul 6,"['Meyers, Lindsay', 'Ginocchio, Christine C', 'Faucett, Aimie N', 'Nolte, Frederick S', 'Gesteland, Per H', 'Leber, Amy', 'Janowiak, Diane', 'Donovan, Virginia', 'Dien Bard, Jennifer', 'Spitzer, Silvia', 'Stellrecht, Kathleen A', 'Salimnia, Hossein', 'Selvarangan, Rangaraj', 'Juretschko, Stefan', 'Daly, Judy A', 'Wallentine, Jeremy C', 'Lindsey, Kristy', 'Moore, Franklin', 'Reed, Sharon L', 'Aguero-Rosenfeld, Maria', 'Fey, Paul D', 'Storch, Gregory A', 'Melnick, Steve J', 'Robinson, Christine C', 'Meredith, Jennifer F', 'Cook, Camille V', 'Nelson, Robert K', 'Jones, Jay D', 'Scarpino, Samuel V', 'Althouse, Benjamin M', 'Ririe, Kirk M', 'Malin, Bradley A', 'Poritz, Mark A']",JMIR Public Health Surveill,,,False
ee1d9f63c87d1f5f3505c55762490b884ebecb86,PMC,Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates,http://dx.doi.org/10.1186/s12985-018-1026-3,PMC6056916,30041659,CC BY,"BACKGROUND: A new promising therapeutic approach has emerged for patients chronically infected by the hepatitis B virus (HBV) with the development of a non-replicative adenovirus vector vaccine candidate (Ad-HBV). The vaccine encodes a fusion protein composed of a truncated HBV core protein, mutated polymerase protein, and two envelope domains. In this study, we assessed the immunogenicity of Ad-HBV administered to cynomolgus monkeys during a non-clinical safety assessment. METHODS: The virus was subcutaneously administered at 1.0 × 10(9) viral particles (VP)/animal (low-dose group), 1.0 × 10(10) VP/animal (mid-dose group), and 1.0 × 10(11) VP/animal (high-dose group); the control groups were administered an Ad5-null virus (1.0 × 10(11) VP/animal) and saline only. RESULTS: Except for inflammatory cell infiltration under the skin at the injection sites and transient elevation of body temperature and serum albumin, no Ad-HBV-related toxic effects were noted in any treatment group. Moreover, interferon (IFN)-γ enzyme-linked immunospot assays showed that Ad-HBV induced the targeting of T cells to a broad spectrum of HBV-specific epitopes spanning all three of the selected HBV immunogens (core, polymerase, and envelope domains) in a dose-dependent manner. Although anti-Ad antibody was produced in all groups (except for the saline control), the antibody titers were significantly lower in the high-dose Ad-HBV group than in the group that received the same dose of the Ad-null empty vector. In addition, the IFN-γ and IL-2 expression levels in the liver were significantly improved for the mid-dose, high-dose, and Ad-null control group (p < 0.05), but not for the low-dose group. CONCLUSIONS: Taken together, this safety assessment indicates that the Ad-HBV candidate vaccine is a potent specific immunotherapeutic agent, supporting its further clinical development as an anti-HBV infection vaccine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1026-3) contains supplementary material, which is available to authorized users.",2018 Jul 24,"['Zhang, Xuefeng', 'Wang, Jing', 'Lu, Jing', 'Li, Rongrong', 'Zhao, Shuli']",Virol J,,,False
48b729d80c27269a5adae142a765824b20790c02,PMC,Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates,http://dx.doi.org/10.1186/s12985-018-1026-3,PMC6056916,30041659,CC BY,"BACKGROUND: A new promising therapeutic approach has emerged for patients chronically infected by the hepatitis B virus (HBV) with the development of a non-replicative adenovirus vector vaccine candidate (Ad-HBV). The vaccine encodes a fusion protein composed of a truncated HBV core protein, mutated polymerase protein, and two envelope domains. In this study, we assessed the immunogenicity of Ad-HBV administered to cynomolgus monkeys during a non-clinical safety assessment. METHODS: The virus was subcutaneously administered at 1.0 × 10(9) viral particles (VP)/animal (low-dose group), 1.0 × 10(10) VP/animal (mid-dose group), and 1.0 × 10(11) VP/animal (high-dose group); the control groups were administered an Ad5-null virus (1.0 × 10(11) VP/animal) and saline only. RESULTS: Except for inflammatory cell infiltration under the skin at the injection sites and transient elevation of body temperature and serum albumin, no Ad-HBV-related toxic effects were noted in any treatment group. Moreover, interferon (IFN)-γ enzyme-linked immunospot assays showed that Ad-HBV induced the targeting of T cells to a broad spectrum of HBV-specific epitopes spanning all three of the selected HBV immunogens (core, polymerase, and envelope domains) in a dose-dependent manner. Although anti-Ad antibody was produced in all groups (except for the saline control), the antibody titers were significantly lower in the high-dose Ad-HBV group than in the group that received the same dose of the Ad-null empty vector. In addition, the IFN-γ and IL-2 expression levels in the liver were significantly improved for the mid-dose, high-dose, and Ad-null control group (p < 0.05), but not for the low-dose group. CONCLUSIONS: Taken together, this safety assessment indicates that the Ad-HBV candidate vaccine is a potent specific immunotherapeutic agent, supporting its further clinical development as an anti-HBV infection vaccine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1026-3) contains supplementary material, which is available to authorized users.",2018 Jul 24,"['Zhang, Xuefeng', 'Wang, Jing', 'Lu, Jing', 'Li, Rongrong', 'Zhao, Shuli']",Virol J,,,False
a1300c6b3c6b9969c3425a9a525f671335e65bc6,PMC,Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates,http://dx.doi.org/10.1186/s12985-018-1026-3,PMC6056916,30041659,CC BY,"BACKGROUND: A new promising therapeutic approach has emerged for patients chronically infected by the hepatitis B virus (HBV) with the development of a non-replicative adenovirus vector vaccine candidate (Ad-HBV). The vaccine encodes a fusion protein composed of a truncated HBV core protein, mutated polymerase protein, and two envelope domains. In this study, we assessed the immunogenicity of Ad-HBV administered to cynomolgus monkeys during a non-clinical safety assessment. METHODS: The virus was subcutaneously administered at 1.0 × 10(9) viral particles (VP)/animal (low-dose group), 1.0 × 10(10) VP/animal (mid-dose group), and 1.0 × 10(11) VP/animal (high-dose group); the control groups were administered an Ad5-null virus (1.0 × 10(11) VP/animal) and saline only. RESULTS: Except for inflammatory cell infiltration under the skin at the injection sites and transient elevation of body temperature and serum albumin, no Ad-HBV-related toxic effects were noted in any treatment group. Moreover, interferon (IFN)-γ enzyme-linked immunospot assays showed that Ad-HBV induced the targeting of T cells to a broad spectrum of HBV-specific epitopes spanning all three of the selected HBV immunogens (core, polymerase, and envelope domains) in a dose-dependent manner. Although anti-Ad antibody was produced in all groups (except for the saline control), the antibody titers were significantly lower in the high-dose Ad-HBV group than in the group that received the same dose of the Ad-null empty vector. In addition, the IFN-γ and IL-2 expression levels in the liver were significantly improved for the mid-dose, high-dose, and Ad-null control group (p < 0.05), but not for the low-dose group. CONCLUSIONS: Taken together, this safety assessment indicates that the Ad-HBV candidate vaccine is a potent specific immunotherapeutic agent, supporting its further clinical development as an anti-HBV infection vaccine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1026-3) contains supplementary material, which is available to authorized users.",2018 Jul 24,"['Zhang, Xuefeng', 'Wang, Jing', 'Lu, Jing', 'Li, Rongrong', 'Zhao, Shuli']",Virol J,,,False
03bb746ba6fb4c250b5f8f9ff0e5013b2c49b8f7,PMC,Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates,http://dx.doi.org/10.1186/s12985-018-1026-3,PMC6056916,30041659,CC BY,"BACKGROUND: A new promising therapeutic approach has emerged for patients chronically infected by the hepatitis B virus (HBV) with the development of a non-replicative adenovirus vector vaccine candidate (Ad-HBV). The vaccine encodes a fusion protein composed of a truncated HBV core protein, mutated polymerase protein, and two envelope domains. In this study, we assessed the immunogenicity of Ad-HBV administered to cynomolgus monkeys during a non-clinical safety assessment. METHODS: The virus was subcutaneously administered at 1.0 × 10(9) viral particles (VP)/animal (low-dose group), 1.0 × 10(10) VP/animal (mid-dose group), and 1.0 × 10(11) VP/animal (high-dose group); the control groups were administered an Ad5-null virus (1.0 × 10(11) VP/animal) and saline only. RESULTS: Except for inflammatory cell infiltration under the skin at the injection sites and transient elevation of body temperature and serum albumin, no Ad-HBV-related toxic effects were noted in any treatment group. Moreover, interferon (IFN)-γ enzyme-linked immunospot assays showed that Ad-HBV induced the targeting of T cells to a broad spectrum of HBV-specific epitopes spanning all three of the selected HBV immunogens (core, polymerase, and envelope domains) in a dose-dependent manner. Although anti-Ad antibody was produced in all groups (except for the saline control), the antibody titers were significantly lower in the high-dose Ad-HBV group than in the group that received the same dose of the Ad-null empty vector. In addition, the IFN-γ and IL-2 expression levels in the liver were significantly improved for the mid-dose, high-dose, and Ad-null control group (p < 0.05), but not for the low-dose group. CONCLUSIONS: Taken together, this safety assessment indicates that the Ad-HBV candidate vaccine is a potent specific immunotherapeutic agent, supporting its further clinical development as an anti-HBV infection vaccine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1026-3) contains supplementary material, which is available to authorized users.",2018 Jul 24,"['Zhang, Xuefeng', 'Wang, Jing', 'Lu, Jing', 'Li, Rongrong', 'Zhao, Shuli']",Virol J,,,True
fcc2ab177ea2abdc579c01dbd48ff43cf65d65d7,PMC,Extra Dose of Vitamin C Based on a Daily Supplementation Shortens the Common Cold: A Meta-Analysis of 9 Randomized Controlled Trials,http://dx.doi.org/10.1155/2018/1837634,PMC6057395,30069463,CC BY,"AIM: To investigate whether vitamin C is effective in the treatment of the common cold. METHOD: After systematically searching the National Library of Medicine (PubMed), Cochrane Library, Elsevier, China National Knowledge Infrastructure (CNKI), VIP databases, and WANFANG databases, 9 randomized placebo-controlled trials were included in our meta-analysis in RevMan 5.3 software, all of which were in English. RESULTS: In the evaluation of vitamin C, administration of extra therapeutic doses at the onset of cold despite routine supplementation was found to help reduce its duration (mean difference (MD) = -0.56, 95% confidence interval (CI) [-1.03, -0.10], and P = 0.02), shorten the time of confinement indoors (MD = -0.41, 95% CI [-0.62, -0.19], and P = 0.0002), and relieve the symptoms associated with it, including chest pain (MD = -0.40, 95% CI [-0.77, -0.03], and P = 0.03), fever (MD = -0.45, 95% CI [-0.78, -0.11], and P = 0.009), and chills (MD = -0.36, 95% CI [-0.65, -0.07], and P = 0.01). CONCLUSIONS: Extra doses of vitamin C could benefit some patients who contract the common cold despite taking daily vitamin C supplements.",2018 Jul 5,"['Ran, Li', 'Zhao, Wenli', 'Wang, Jingxia', 'Wang, Hongwu', 'Zhao, Ye', 'Tseng, Yiider', 'Bu, Huaien']",Biomed Res Int,,,False
90570e69d4ac4b2e72385123ba09f6b754707b61,PMC,Extra Dose of Vitamin C Based on a Daily Supplementation Shortens the Common Cold: A Meta-Analysis of 9 Randomized Controlled Trials,http://dx.doi.org/10.1155/2018/1837634,PMC6057395,30069463,CC BY,"AIM: To investigate whether vitamin C is effective in the treatment of the common cold. METHOD: After systematically searching the National Library of Medicine (PubMed), Cochrane Library, Elsevier, China National Knowledge Infrastructure (CNKI), VIP databases, and WANFANG databases, 9 randomized placebo-controlled trials were included in our meta-analysis in RevMan 5.3 software, all of which were in English. RESULTS: In the evaluation of vitamin C, administration of extra therapeutic doses at the onset of cold despite routine supplementation was found to help reduce its duration (mean difference (MD) = -0.56, 95% confidence interval (CI) [-1.03, -0.10], and P = 0.02), shorten the time of confinement indoors (MD = -0.41, 95% CI [-0.62, -0.19], and P = 0.0002), and relieve the symptoms associated with it, including chest pain (MD = -0.40, 95% CI [-0.77, -0.03], and P = 0.03), fever (MD = -0.45, 95% CI [-0.78, -0.11], and P = 0.009), and chills (MD = -0.36, 95% CI [-0.65, -0.07], and P = 0.01). CONCLUSIONS: Extra doses of vitamin C could benefit some patients who contract the common cold despite taking daily vitamin C supplements.",2018 Jul 5,"['Ran, Li', 'Zhao, Wenli', 'Wang, Jingxia', 'Wang, Hongwu', 'Zhao, Ye', 'Tseng, Yiider', 'Bu, Huaien']",Biomed Res Int,,,True
b16e9ad986a7b19e35e008a79293bba8fb2c6787,PMC,A Note on the Risk of Infections Invading Unaffected Regions,http://dx.doi.org/10.1155/2018/6289681,PMC6057402,30073032,CC BY,"We present two probabilistic models to estimate the risk of introducing infectious diseases into previously unaffected countries/regions by infective travellers. We analyse two distinct situations, one dealing with a directly transmitted infection (measles in Italy in 2017) and one dealing with a vector-borne infection (Zika virus in Rio de Janeiro, which may happen in the future). To calculate the risk in the first scenario, we used a simple, nonhomogeneous birth process. The second model proposed in this paper provides a way to calculate the probability that local mosquitoes become infected by the arrival of a single infective traveller during his/her infectiousness period. The result of the risk of measles invasion of Italy was of 93% and the result of the risk of Zika virus invasion of Rio de Janeiro was of 22%.",2018 Jul 4,"['Amaku, Marcos', 'Coutinho, Francisco Antonio Bezerra', 'Armstrong, Margaret', 'Massad, Eduardo']",Comput Math Methods Med,,,True
17bbe32558609da8c1aceab2b751383aa9c3c18b,PMC,Functional Characterization of Plasmodium falciparum Surface-Related Antigen as a Potential Blood-Stage Vaccine Target,http://dx.doi.org/10.1093/infdis/jiy222,PMC6057521,29912472,CC BY,"Plasmodium falciparum erythrocyte invasion is a multistep process that involves a spectrum of interactions that are not well characterized. We have characterized a 113-kDa immunogenic protein, PF3D7_1431400 (PF14_0293), that possesses coiled-coil structures. The protein is localized on the surfaces of both merozoites and gametocytes, hence the name Plasmodium falciparum surface-related antigen (PfSRA). The processed 32-kDa fragment of PfSRA binds normal human erythrocytes with different sensitivities to enzyme treatments. Temporal imaging from initial attachment to internalization of viable merozoites revealed that a fragment of PfSRA, along with PfMSP1(19,) is internalized after invasion. Moreover, parasite growth inhibition assays showed that PfSRA P1 antibodies potently inhibited erythrocyte invasion of both sialic acid–dependent and –independent parasite strains. Also, immunoepidemiological studies show that malaria-infected populations have naturally acquired antibodies against PfSRA. Overall, the results demonstrate that PfSRA has the structural and functional characteristics of a very promising target for vaccine development.",2018 Sep 1,"['Amlabu, Emmanuel', 'Mensah-Brown, Henrietta', 'Nyarko, Prince B', 'Akuh, Ojo-ajogu', 'Opoku, Grace', 'Ilani, Philip', 'Oyagbenro, Richard', 'Asiedu, Kwame', 'Aniweh, Yaw', 'Awandare, Gordon A']",J Infect Dis,,,True
5a3f46d6fe292e51aa8ad833905cd913ade65caa,PMC,Acute disseminated encephalomyelitis: a call to the clinicians for keeping this rare condition on clinical radar,http://dx.doi.org/10.11604/pamj.2018.29.138.13942,PMC6057575,30050602,CC BY,"Acute disseminated encephalomyelitis is a rare disease of central nervous system, which can present with a variety of clinical manifestations. That is why first attack of ADEM, in particular remains a diagnostic puzzle. Early anticipation and diagnosis is important for better outcomes. We present a case of acute disseminated encephalomyelitis which initially had atypical clinical features with cough, expectoration, fever and later manifested strange neurological features, diagnosed to be a case of acute disseminated encephalomyelitis based on radio-imaging.",2018 Mar 2,"['Chaudhry, Liaqat Ali', 'Babur, Waseem', 'Chaudhry, Ghazala Aslam', 'Al-Atawi, Feddah Eid', 'Robert, Asirvatham Alwin']",Pan Afr Med J,,,True
14ae1c8c866fcbdad5e965f296a90a8cbf41f689,PMC,An integrated analysis of membrane remodeling during porcine reproductive and respiratory syndrome virus replication and assembly,http://dx.doi.org/10.1371/journal.pone.0200919,PMC6057628,30040832,CC BY,"BACKGROUND: Recently, three-dimensional (3D) imaging techniques have been used to detect viral invasion and the appearance of specialized structures established in virus-infected cells. These methods have had a positive impact in the field of virology and helped to further our knowledge of how viruses invade cells. Nearly all positive-strand RNA viruses propagate their viral genomes in part through intracellular membranes. Porcine reproductive and respiratory syndrome virus (PRRSV), an Arterivirus, accumulates viral RNA that forms replication complexes (RCs) in infected cells. In this study, using immunofluorescence and electron microscopy (EM), we dissected PRRSV-induced membrane structures in infected cells and determined the correlations between PRRSV particles and vesicles stimulated by PRRSV to understand the structural and dynamic aspects of PRRSV infection. METHODS: We identified the appropriate time point by determining the 50% tissue culture infectious dose (TCID50) and using qRT-PCR and Western blotting. The co-localization of viruses and organelles was determined by immunofluorescence and immune-electron microscopy (IEM). The ultrastructure of cells infected by PRRSV was observed using EM and electron tomography (ET). RESULTS: In our study, we found that PRRSV dsRNA was located at the endoplasmic reticulum (ER) and autophagosomes; in addition, the N protein was located at the mitochondria, ER and autophagosomes. Vesicles induced by PRRSV appeared at 16 hours post-infection (h.p.i.) and increased in size with time during the infection period. In addition, our findings demonstrated that the virus vesicles originated from the ER, and these two organelle structures connected with each other to form a reticulovesicular network (RVN) that provided a site for virus replication and assembly. CONCLUSION: Our results revealed that membrane vesicles induced by PRRSV were derived from the ER. The vesicles may provide a location for PRRSV replication and assembly.",2018 Jul 24,"['Zhang, Wei', 'Chen, Keren', 'Zhang, Xueqing', 'Guo, Chunhe', 'Chen, Yaosheng', 'Liu, Xiaohong']",PLoS One,,,True
6799e37b5fda2d18292b86b6a6c7ba1eb185d018,PMC,Late Endosomal/Lysosomal Cholesterol Accumulation Is a Host Cell-Protective Mechanism Inhibiting Endosomal Escape of Influenza A Virus,http://dx.doi.org/10.1128/mBio.01345-18,PMC6058292,30042202,CC BY,"To transfer the viral genome into the host cell cytoplasm, internalized influenza A virus (IAV) particles depend on the fusion of the IAV envelope with host endosomal membranes. The antiviral host interferon (IFN) response includes the upregulation of interferon-induced transmembrane protein 3 (IFITM3), which inhibits the release of the viral content into the cytosol. Although IFITM3 induction occurs concomitantly with late endosomal/lysosomal (LE/L) cholesterol accumulation, the functional significance of this process is not well understood. Here we report that LE/L cholesterol accumulation itself plays a pivotal role in the early antiviral defense. We demonstrate that inducing LE/L cholesterol accumulation is antiviral in non-IFN-primed cells, restricting incoming IAV particles and impairing mixing of IAV/endosomal membrane lipids. Our results establish a protective function of LE/L cholesterol accumulation and suggest endosomal cholesterol balance as a possible antiviral target.",2018 Jul 24,"['Kühnl, Alexander', 'Musiol, Agnes', 'Heitzig, Nicole', 'Johnson, Danielle E.', 'Ehrhardt, Christina', 'Grewal, Thomas', 'Gerke, Volker', 'Ludwig, Stephan', 'Rescher, Ursula']",mBio,,,True
baacfd6d9d2bfd543bc3d8e9b2be4f566a5bf458,PMC,Late Endosomal/Lysosomal Cholesterol Accumulation Is a Host Cell-Protective Mechanism Inhibiting Endosomal Escape of Influenza A Virus,http://dx.doi.org/10.1128/mBio.01345-18,PMC6058292,30042202,CC BY,"To transfer the viral genome into the host cell cytoplasm, internalized influenza A virus (IAV) particles depend on the fusion of the IAV envelope with host endosomal membranes. The antiviral host interferon (IFN) response includes the upregulation of interferon-induced transmembrane protein 3 (IFITM3), which inhibits the release of the viral content into the cytosol. Although IFITM3 induction occurs concomitantly with late endosomal/lysosomal (LE/L) cholesterol accumulation, the functional significance of this process is not well understood. Here we report that LE/L cholesterol accumulation itself plays a pivotal role in the early antiviral defense. We demonstrate that inducing LE/L cholesterol accumulation is antiviral in non-IFN-primed cells, restricting incoming IAV particles and impairing mixing of IAV/endosomal membrane lipids. Our results establish a protective function of LE/L cholesterol accumulation and suggest endosomal cholesterol balance as a possible antiviral target.",2018 Jul 24,"['Kühnl, Alexander', 'Musiol, Agnes', 'Heitzig, Nicole', 'Johnson, Danielle E.', 'Ehrhardt, Christina', 'Grewal, Thomas', 'Gerke, Volker', 'Ludwig, Stephan', 'Rescher, Ursula']",mBio,,,False
cde887d487cd9685a4bdbf8bced930e600bc34e6,PMC,Late Endosomal/Lysosomal Cholesterol Accumulation Is a Host Cell-Protective Mechanism Inhibiting Endosomal Escape of Influenza A Virus,http://dx.doi.org/10.1128/mBio.01345-18,PMC6058292,30042202,CC BY,"To transfer the viral genome into the host cell cytoplasm, internalized influenza A virus (IAV) particles depend on the fusion of the IAV envelope with host endosomal membranes. The antiviral host interferon (IFN) response includes the upregulation of interferon-induced transmembrane protein 3 (IFITM3), which inhibits the release of the viral content into the cytosol. Although IFITM3 induction occurs concomitantly with late endosomal/lysosomal (LE/L) cholesterol accumulation, the functional significance of this process is not well understood. Here we report that LE/L cholesterol accumulation itself plays a pivotal role in the early antiviral defense. We demonstrate that inducing LE/L cholesterol accumulation is antiviral in non-IFN-primed cells, restricting incoming IAV particles and impairing mixing of IAV/endosomal membrane lipids. Our results establish a protective function of LE/L cholesterol accumulation and suggest endosomal cholesterol balance as a possible antiviral target.",2018 Jul 24,"['Kühnl, Alexander', 'Musiol, Agnes', 'Heitzig, Nicole', 'Johnson, Danielle E.', 'Ehrhardt, Christina', 'Grewal, Thomas', 'Gerke, Volker', 'Ludwig, Stephan', 'Rescher, Ursula']",mBio,,,False
fbab96d98840777415ef5eb1d1f48dc7b799ebd5,PMC,Late Endosomal/Lysosomal Cholesterol Accumulation Is a Host Cell-Protective Mechanism Inhibiting Endosomal Escape of Influenza A Virus,http://dx.doi.org/10.1128/mBio.01345-18,PMC6058292,30042202,CC BY,"To transfer the viral genome into the host cell cytoplasm, internalized influenza A virus (IAV) particles depend on the fusion of the IAV envelope with host endosomal membranes. The antiviral host interferon (IFN) response includes the upregulation of interferon-induced transmembrane protein 3 (IFITM3), which inhibits the release of the viral content into the cytosol. Although IFITM3 induction occurs concomitantly with late endosomal/lysosomal (LE/L) cholesterol accumulation, the functional significance of this process is not well understood. Here we report that LE/L cholesterol accumulation itself plays a pivotal role in the early antiviral defense. We demonstrate that inducing LE/L cholesterol accumulation is antiviral in non-IFN-primed cells, restricting incoming IAV particles and impairing mixing of IAV/endosomal membrane lipids. Our results establish a protective function of LE/L cholesterol accumulation and suggest endosomal cholesterol balance as a possible antiviral target.",2018 Jul 24,"['Kühnl, Alexander', 'Musiol, Agnes', 'Heitzig, Nicole', 'Johnson, Danielle E.', 'Ehrhardt, Christina', 'Grewal, Thomas', 'Gerke, Volker', 'Ludwig, Stephan', 'Rescher, Ursula']",mBio,,,False
c6f838e750028292d64887910f3bb63cd98b16e1,PMC,Late Endosomal/Lysosomal Cholesterol Accumulation Is a Host Cell-Protective Mechanism Inhibiting Endosomal Escape of Influenza A Virus,http://dx.doi.org/10.1128/mBio.01345-18,PMC6058292,30042202,CC BY,"To transfer the viral genome into the host cell cytoplasm, internalized influenza A virus (IAV) particles depend on the fusion of the IAV envelope with host endosomal membranes. The antiviral host interferon (IFN) response includes the upregulation of interferon-induced transmembrane protein 3 (IFITM3), which inhibits the release of the viral content into the cytosol. Although IFITM3 induction occurs concomitantly with late endosomal/lysosomal (LE/L) cholesterol accumulation, the functional significance of this process is not well understood. Here we report that LE/L cholesterol accumulation itself plays a pivotal role in the early antiviral defense. We demonstrate that inducing LE/L cholesterol accumulation is antiviral in non-IFN-primed cells, restricting incoming IAV particles and impairing mixing of IAV/endosomal membrane lipids. Our results establish a protective function of LE/L cholesterol accumulation and suggest endosomal cholesterol balance as a possible antiviral target.",2018 Jul 24,"['Kühnl, Alexander', 'Musiol, Agnes', 'Heitzig, Nicole', 'Johnson, Danielle E.', 'Ehrhardt, Christina', 'Grewal, Thomas', 'Gerke, Volker', 'Ludwig, Stephan', 'Rescher, Ursula']",mBio,,,False
78a8d488d2fa21bd3fedcd4534718376e9333406,PMC,Transmission of rhinovirus in the Utah BIG-LoVE families: Consequences of age and household structure,http://dx.doi.org/10.1371/journal.pone.0199388,PMC6059387,30044794,CC BY,"BACKGROUND: Common cold viruses create significant health and financial burdens, and understanding key loci of transmission would help focus control strategies. This study (1) examines factors that influence when individuals transition from a negative to positive test (acquisition) or a positive to negative test (loss) of rhinovirus (HRV) and other respiratory tract viruses in 26 households followed weekly for one year, (2) investigates evidence for intrahousehold and interhousehold transmission and the characteristics of individuals implicated in transmission, and (3) builds data-based simulation models to identify factors that most strongly affect patterns of prevalence. METHODS: We detected HRV, coronavirus, paramyxovirus, influenza and bocavirus with the FilmArray polymerase chain reaction (PCR) platform (BioFire Diagnostics, LLC). We used logistic regression to find covariates affecting acquisition or loss of HRV including demographic characteristics of individuals, their household, their current infection status, and prevalence within their household and across the population. We apply generalized linear mixed models to test robustness of results. RESULTS: Acquisition of HRV was less probable in older individuals and those infected with a coronavirus, and higher with a higher proportion of other household members infected. Loss of HRV is reduced with a higher proportion of other household members infected. Within households, only children and symptomatic individuals show evidence for transmission, while between households only a higher number of infected older children (ages 5-19) increases the probability of acquisition. Coronaviruses, paramyxoviruses and bocavirus also show evidence of intrahousehold transmission. Simulations show that age-dependent susceptibility and transmission have the largest effects on mean HRV prevalence. CONCLUSIONS: Children are most likely to acquire and most likely to transmit HRV both within and between households, with infectiousness concentrated in symptomatic children. Simulations predict that the spread of HRV and other respiratory tract viruses can be reduced but not eliminated by practices within the home.",2018 Jul 25,"['Adler, Frederick R.', 'Stockmann, Chris', 'Ampofo, Krow', 'Pavia, Andrew T.', 'Byington, Carrie L.']",PLoS One,,,True
ab7278ce795b0738f2dcfee4b958083251836555,PMC,High-level expression of the HIV entry inhibitor griffithsin from the plastid genome and retention of biological activity in dried tobacco leaves,http://dx.doi.org/10.1007/s11103-018-0744-7,PMC6061503,29948657,CC BY,"KEY MESSAGE: The potent anti-HIV microbicide griffithsin was expressed to high levels in tobacco chloroplasts, enabling efficient purification from both fresh and dried biomass, thus providing storable material for inexpensive production and scale-up on demand. ABSTRACT: The global HIV epidemic continues to grow, with 1.8 million new infections occurring per year. In the absence of a cure and an AIDS vaccine, there is a pressing need to prevent new infections in order to curb the disease. Topical microbicides that block viral entry into human cells can potentially prevent HIV infection. The antiviral lectin griffithsin has been identified as a highly potent inhibitor of HIV entry into human cells. Here we have explored the possibility to use transplastomic plants as an inexpensive production platform for griffithsin. We show that griffithsin accumulates in stably transformed tobacco chloroplasts to up to 5% of the total soluble protein of the plant. Griffithsin can be easily purified from leaf material and shows similarly high virus neutralization activity as griffithsin protein recombinantly expressed in bacteria. We also show that dried tobacco provides a storable source material for griffithsin purification, thus enabling quick scale-up of production on demand. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11103-018-0744-7) contains supplementary material, which is available to authorized users.",2018 Jun 9,"['Hoelscher, Matthijs', 'Tiller, Nadine', 'Teh, Audrey Y.-H.', 'Wu, Guo-Zhang', 'Ma, Julian K-C.', 'Bock, Ralph']",Plant Mol Biol,,,False
8f4aac04423c7ebb955c7f006665728fe95f1498,PMC,High-level expression of the HIV entry inhibitor griffithsin from the plastid genome and retention of biological activity in dried tobacco leaves,http://dx.doi.org/10.1007/s11103-018-0744-7,PMC6061503,29948657,CC BY,"KEY MESSAGE: The potent anti-HIV microbicide griffithsin was expressed to high levels in tobacco chloroplasts, enabling efficient purification from both fresh and dried biomass, thus providing storable material for inexpensive production and scale-up on demand. ABSTRACT: The global HIV epidemic continues to grow, with 1.8 million new infections occurring per year. In the absence of a cure and an AIDS vaccine, there is a pressing need to prevent new infections in order to curb the disease. Topical microbicides that block viral entry into human cells can potentially prevent HIV infection. The antiviral lectin griffithsin has been identified as a highly potent inhibitor of HIV entry into human cells. Here we have explored the possibility to use transplastomic plants as an inexpensive production platform for griffithsin. We show that griffithsin accumulates in stably transformed tobacco chloroplasts to up to 5% of the total soluble protein of the plant. Griffithsin can be easily purified from leaf material and shows similarly high virus neutralization activity as griffithsin protein recombinantly expressed in bacteria. We also show that dried tobacco provides a storable source material for griffithsin purification, thus enabling quick scale-up of production on demand. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11103-018-0744-7) contains supplementary material, which is available to authorized users.",2018 Jun 9,"['Hoelscher, Matthijs', 'Tiller, Nadine', 'Teh, Audrey Y.-H.', 'Wu, Guo-Zhang', 'Ma, Julian K-C.', 'Bock, Ralph']",Plant Mol Biol,,,True
fd80a87a02d130989492acfc82db606ee470ab53,PMC,The conserved stem-loop II structure at the 3' untranslated region of Japanese encephalitis virus genome is required for the formation of subgenomic flaviviral RNA,http://dx.doi.org/10.1371/journal.pone.0201250,PMC6062100,30048535,CC BY,"Flaviviruses accumulate abundant subgenomic RNA (sfRNA) in infected cells. It has been reported that sfRNA results from stalling of host 5’-to-3’ exoribonuclease XRN1 at the highly structured RNA of the 3’ untranslated region (UTR). Although XRN1 digestion of a 3’-terminal 800-nt RNA could stall at a position to generate the sfRNA in vitro, we found that knocking out XRN1 had no effect on the accumulation of sfRNA in Japanese encephalitis virus (JEV) infected cells. Mutagenesis studies revealed that the stemloop II (SLII) at the 3’ UTR is required for the accumulation of sfRNA. According to the results of an in vitro RNA-dependent RNA polymerase (RdRp) assay, the (-)10431-10566 RNA fragment, containing the putative promoter on the antigenome for the sfRNA transcription, binds to RdRp protein and exhibits a strong promoter activity. Taken together, our results indicate that the JEV sfRNA could be transcribed initially and then be trimmed by XRN1 or other unidentified exoribonucleases.",2018 Jul 26,"['Chen, Yi-Shiuan', 'Fan, Yi-Hsin', 'Tien, Chih-Feng', 'Yueh, Andrew', 'Chang, Ruey-Yi']",PLoS One,,,True
936e6e20342454e2646bd840d70148c893262146,PMC,Nucleocapsid protein-based vaccine provides protection in mice against lethal Crimean-Congo hemorrhagic fever virus challenge,http://dx.doi.org/10.1371/journal.pntd.0006628,PMC6062107,30011277,CC0,"Crimean-Congo hemorrhagic fever (CCHF) is an acute, often fatal viral disease characterized by rapid onset of febrile symptoms followed by hemorrhagic manifestations. The etiologic agent, CCHF orthonairovirus (CCHFV), can infect several mammals in nature but only seems to cause clinical disease in humans. Over the past two decades there has been an increase in total number of CCHF case reports, including imported CCHF patients, and an expansion of CCHF endemic areas. Despite its increased public health burden there are currently no licensed vaccines or treatments to prevent CCHF. We here report the development and assessment of the protective efficacy of an adenovirus (Ad)-based vaccine expressing the nucleocapsid protein (N) of CCHFV (Ad-N) in a lethal immunocompromised mouse model of CCHF. The results show that Ad-N can protect mice from CCHF mortality and that this platform should be considered for future CCHFV vaccine strategies.",2018 Jul 16,"['Zivcec, Marko', 'Safronetz, David', 'Scott, Dana P.', 'Robertson, Shelly', 'Feldmann, Heinz']",PLoS Negl Trop Dis,,,True
b9c267b7dcc9a8348248c04a8bf604aa52926101,PMC,Intrathecal B Cells in MS Have Significantly Greater Lymphangiogenic Potential Compared to B Cells Derived From Non-MS Subjects,http://dx.doi.org/10.3389/fneur.2018.00554,PMC6062589,30079049,CC BY,"Although B cell depletion is an effective therapy of multiple sclerosis (MS), the pathogenic functions of B cells in MS remain incompletely understood. We asked whether cerebrospinal fluid (CSF) B cells in MS secrete different cytokines than control-subject B cells and whether cytokine secretion affects MS phenotype. We blindly studied CSF B cells after their immortalization by Epstein-Barr Virus (EBV) in prospectively-collected MS patients and control subjects with other inflammatory-(OIND) or non-inflammatory neurological diseases (NIND) and healthy volunteers (HV). The pilot cohort (n = 80) was analyzed using intracellular cytokine staining (n = 101 B cell lines [BCL] derived from 35 out of 80 subjects). We validated differences in cytokine production in newly-generated CSF BCL (n = 207 BCL derived from subsequent 112 prospectively-recruited subjects representing validation cohort), using ELISA enhanced by objective, flow-cytometry-based B cell counting. After unblinding the pilot cohort, the immortalization efficiency was almost 5 times higher in MS patients compared to controls (p < 0.001). MS subjects' BCLs produced significantly more vascular endothelial growth factor (VEGF) compared to control BCLs. Progressive MS patients BCLs produced significantly more tumor necrosis factor (TNF)-α and lymphotoxin (LT)-α than BCL from relapsing-remitting MS (RRMS) patients. In the validation cohort, we observed lower secretion of IL-1β in RRMS patients, compared to all other diagnostic categories. The validation cohort validated enhanced VEGF-C production by BCL from RRMS patients and higher TNF-α and LT-α secretion by BCL from progressive MS. No significant differences among diagnostic categories were observed in secretion of IL-6 or GM-CSF. However, B cell secretion of IL-1β, TNF-α, and GM-CSF correlated significantly with the rate of accumulation of disability measured by MS disease severity scale (MS-DSS). Finally, all three cytokines with increased secretion in different stages of MS (i.e., VEGF-C, TNF-α, and LT-α) enhance lymphangiogenesis, suggesting that intrathecal B cells directly facilitate the formation of tertiary lymphoid follicles, thus compartmentalizing inflammation to the central nervous system.",2018 Jul 20,"['Stein, Jason', 'Xu, Quangang', 'Jackson, Kayla C.', 'Romm, Elena', 'Wuest, Simone C.', 'Kosa, Peter', 'Wu, Tianxia', 'Bielekova, Bibiana']",Front Neurol,,,True
bd18832006ef03fab74bf51388034b7e9605e14a,PMC,"Influenza A Virus Cell Entry, Replication, Virion Assembly and Movement",http://dx.doi.org/10.3389/fimmu.2018.01581,PMC6062596,30079062,CC BY,"Influenza viruses replicate within the nucleus of the host cell. This uncommon RNA virus trait provides influenza with the advantage of access to the nuclear machinery during replication. However, it also increases the complexity of the intracellular trafficking that is required for the viral components to establish a productive infection. The segmentation of the influenza genome makes these additional trafficking requirements especially challenging, as each viral RNA (vRNA) gene segment must navigate the network of cellular membrane barriers during the processes of entry and assembly. To accomplish this goal, influenza A viruses (IAVs) utilize a combination of viral and cellular mechanisms to coordinate the transport of their proteins and the eight vRNA gene segments in and out of the cell. The aim of this review is to present the current mechanistic understanding for how IAVs facilitate cell entry, replication, virion assembly, and intercellular movement, in an effort to highlight some of the unanswered questions regarding the coordination of the IAV infection process.",2018 Jul 20,"['Dou, Dan', 'Revol, Rebecca', 'Östbye, Henrik', 'Wang, Hao', 'Daniels, Robert']",Front Immunol,,,True
958d5304e142a24fffd0ea22672840e340efa309,PMC,Sex Hormones Regulate Innate Immune Cells and Promote Sex Differences in Respiratory Virus Infection,http://dx.doi.org/10.3389/fimmu.2018.01653,PMC6062604,30079065,CC BY,"Sex differences in the incidence and severity of respiratory virus infection are widely documented in humans and murine models and correlate with sex biases in numbers and/or functional responses of innate immune cells in homeostasis and lung infection. Similarly, changes in sex hormone levels upon puberty, pregnancy, and menopause/aging are associated with qualitative and quantitative differences in innate immunity. Immune cells express receptors for estrogens (ERα and ERβ), androgens (AR), and progesterone (PR), and experimental manipulation of sex hormone levels or receptors has revealed that sex hormone receptor activity often underlies sex differences in immune cell numbers and/or functional responses in the respiratory tract. While elegant studies have defined mechanistic roles for sex hormones and receptors in innate immune cells, much remains to be learned about the cellular and molecular mechanisms of action of ER, PR, and AR in myeloid cells and innate lymphocytes to promote the initiation and resolution of antiviral immunity in the lung. Here, we review the literature on sex differences and sex hormone regulation in innate immune cells in the lung in homeostasis and upon respiratory virus infection.",2018 Jul 20,"['Kadel, Sapana', 'Kovats, Susan']",Front Immunol,,,True
edf2997357501734a93c1b7e16d44e86a7d20853,PMC,Identification and characterisation of the CD40-ligand of Sigmodon hispidus,http://dx.doi.org/10.1371/journal.pone.0199067,PMC6063397,30052641,CC BY,"Cotton rats are an important animal model to study infectious diseases. They have demonstrated higher susceptibility to a wider variety of human pathogens than other rodents and are also the animal model of choice for pre-clinical evaluations of some vaccine candidates. However, the genome of cotton rats remains to be fully sequenced, with much fewer genes cloned and characterised compared to other rodent species. Here we report the cloning and characterization of CD40 ligand, whose human and murine counterparts are known to be expressed on a range of cell types including activated T cells and B cells, dendritic cells, granulocytes, macrophages and platelets and exerts a broad array of immune responses. The cDNA for cotton rat CD40L we isolated is comprised of 1104 nucleotides with an open reading frame (ORF) of 783bp coding for a 260 amino acid protein. The recombinant cotton rat CD40L protein was recognized by an antibody against mouse CD40L. Moreover, it demonstrated functional activities on immature bone marrow dendritic cells by upregulating surface maturation markers (CD40, CD54, CD80, and CD86), and increasing IL-6 gene and protein expression. The availability of CD40L gene identity could greatly facilitate mechanistic research on pathogen-induced-immunopathogenesis and vaccine-elicited immune responses.",2018 Jul 27,"['Russell, Marsha S.', 'Muralidharan, Abenaya', 'Larocque, Louise', 'Cao, Jingxin', 'Deschambault, Yvon', 'Varga, Jessie', 'Thulasi Raman, Sathya N.', 'Li, Xuguang']",PLoS One,,,True
76e113fe0eb4a4edd2ca5d93b4595aa77f251e05,PMC,Identification and characterisation of the CD40-ligand of Sigmodon hispidus,http://dx.doi.org/10.1371/journal.pone.0199067,PMC6063397,30052641,CC BY,"Cotton rats are an important animal model to study infectious diseases. They have demonstrated higher susceptibility to a wider variety of human pathogens than other rodents and are also the animal model of choice for pre-clinical evaluations of some vaccine candidates. However, the genome of cotton rats remains to be fully sequenced, with much fewer genes cloned and characterised compared to other rodent species. Here we report the cloning and characterization of CD40 ligand, whose human and murine counterparts are known to be expressed on a range of cell types including activated T cells and B cells, dendritic cells, granulocytes, macrophages and platelets and exerts a broad array of immune responses. The cDNA for cotton rat CD40L we isolated is comprised of 1104 nucleotides with an open reading frame (ORF) of 783bp coding for a 260 amino acid protein. The recombinant cotton rat CD40L protein was recognized by an antibody against mouse CD40L. Moreover, it demonstrated functional activities on immature bone marrow dendritic cells by upregulating surface maturation markers (CD40, CD54, CD80, and CD86), and increasing IL-6 gene and protein expression. The availability of CD40L gene identity could greatly facilitate mechanistic research on pathogen-induced-immunopathogenesis and vaccine-elicited immune responses.",2018 Jul 27,"['Russell, Marsha S.', 'Muralidharan, Abenaya', 'Larocque, Louise', 'Cao, Jingxin', 'Deschambault, Yvon', 'Varga, Jessie', 'Thulasi Raman, Sathya N.', 'Li, Xuguang']",PLoS One,,,False
4223b4aa5481cba972e4cc98fcbd7b67c9f12505,PMC,Identification and characterisation of the CD40-ligand of Sigmodon hispidus,http://dx.doi.org/10.1371/journal.pone.0199067,PMC6063397,30052641,CC BY,"Cotton rats are an important animal model to study infectious diseases. They have demonstrated higher susceptibility to a wider variety of human pathogens than other rodents and are also the animal model of choice for pre-clinical evaluations of some vaccine candidates. However, the genome of cotton rats remains to be fully sequenced, with much fewer genes cloned and characterised compared to other rodent species. Here we report the cloning and characterization of CD40 ligand, whose human and murine counterparts are known to be expressed on a range of cell types including activated T cells and B cells, dendritic cells, granulocytes, macrophages and platelets and exerts a broad array of immune responses. The cDNA for cotton rat CD40L we isolated is comprised of 1104 nucleotides with an open reading frame (ORF) of 783bp coding for a 260 amino acid protein. The recombinant cotton rat CD40L protein was recognized by an antibody against mouse CD40L. Moreover, it demonstrated functional activities on immature bone marrow dendritic cells by upregulating surface maturation markers (CD40, CD54, CD80, and CD86), and increasing IL-6 gene and protein expression. The availability of CD40L gene identity could greatly facilitate mechanistic research on pathogen-induced-immunopathogenesis and vaccine-elicited immune responses.",2018 Jul 27,"['Russell, Marsha S.', 'Muralidharan, Abenaya', 'Larocque, Louise', 'Cao, Jingxin', 'Deschambault, Yvon', 'Varga, Jessie', 'Thulasi Raman, Sathya N.', 'Li, Xuguang']",PLoS One,,,False
cca534a08e2c7de2caee739eaca157706db95289,PMC,Identification and characterisation of the CD40-ligand of Sigmodon hispidus,http://dx.doi.org/10.1371/journal.pone.0199067,PMC6063397,30052641,CC BY,"Cotton rats are an important animal model to study infectious diseases. They have demonstrated higher susceptibility to a wider variety of human pathogens than other rodents and are also the animal model of choice for pre-clinical evaluations of some vaccine candidates. However, the genome of cotton rats remains to be fully sequenced, with much fewer genes cloned and characterised compared to other rodent species. Here we report the cloning and characterization of CD40 ligand, whose human and murine counterparts are known to be expressed on a range of cell types including activated T cells and B cells, dendritic cells, granulocytes, macrophages and platelets and exerts a broad array of immune responses. The cDNA for cotton rat CD40L we isolated is comprised of 1104 nucleotides with an open reading frame (ORF) of 783bp coding for a 260 amino acid protein. The recombinant cotton rat CD40L protein was recognized by an antibody against mouse CD40L. Moreover, it demonstrated functional activities on immature bone marrow dendritic cells by upregulating surface maturation markers (CD40, CD54, CD80, and CD86), and increasing IL-6 gene and protein expression. The availability of CD40L gene identity could greatly facilitate mechanistic research on pathogen-induced-immunopathogenesis and vaccine-elicited immune responses.",2018 Jul 27,"['Russell, Marsha S.', 'Muralidharan, Abenaya', 'Larocque, Louise', 'Cao, Jingxin', 'Deschambault, Yvon', 'Varga, Jessie', 'Thulasi Raman, Sathya N.', 'Li, Xuguang']",PLoS One,,,False
01669153236899edec9fff5fc4fb19a742c3dfef,PMC,"Overview of three influenza seasons in Georgia, 2014–2017",http://dx.doi.org/10.1371/journal.pone.0201207,PMC6063423,30052663,CC BY,"BACKGROUND: Influenza epidemiological and virologic data from Georgia are limited. We aimed to present Influenza Like Illness (ILI) and Severe Acute Respiratory Infection (SARI) surveillance data and characterize influenza viruses circulating in the country over three influenza seasons. METHODS: We analyzed sentinel site ILI and SARI data for the 2014–2017 seasons in Georgia. Patients’ samples were screened by real-time RT-PCR and influenza viruses isolated were characterized antigenically by haemagglutination inhibition assay and genetically by sequencing of HA and NA genes. RESULTS: 32% (397/1248) of ILI and 29% (581/1997) of SARI patients tested were positive for influenza viruses. In 2014–2015 the median week of influenza detection was week 7/2015 with B/Yamagata lineage viruses dominating (79%); in 2015–2016—week 5/2016 was the median with A/H1N1pdm09 viruses prevailing (83%); and in 2016–2017 a bimodal distribution of influenza activity was observed—the first wave was caused by A/H3N2 (55%) with median week 51/2016 and the second by B/Victoria lineage viruses (45%) with median week 9/2017. For ILI, influenza virus detection was highest in children aged 5–14 years while for SARI patients most were aged >15 years and 27 (4.6%) of 581 SARI cases died during the three seasons. Persons aged 30–64 years had the highest risk of fatal outcome, notably those infected with A/H1N1pdm09 (OR 11.41, CI 3.94–33.04, p<0.001). A/H1N1pdm09 viruses analyzed by gene sequencing fell into genetic groups 6B and 6B.1; A/H3N2 viruses belonged to genetic subclades 3C.3b, 3C.3a, 3C.2a and 3C.2a1; B/Yamagata lineage viruses were of clade 3 and B/Victoria lineage viruses fell in clade1A. CONCLUSION: In Georgia influenza virus activity occurred mainly from December through March in all seasons, with varying peak weeks and predominating viruses. Around one third of ILI/ SARI cases were associated with influenza caused by antigenically and genetically distinct influenza viruses over the course of the three seasons.",2018 Jul 27,"['Machablishvili, Ann', 'Chakhunashvili, Giorgi', 'Zakhashvili, Khatuna', 'Karseladze, Irakli', 'Tarkhan-Mouravi, Olgha', 'Gavashelidze, Mari', 'Jashiashvili, Tamar', 'Sabadze, Lela', 'Imnadze, Paata', 'Daniels, Rodney S.', 'Ermetal, Burcu', 'McCauley, John W.']",PLoS One,,,True
9271f0b0a1dc37e0a0fa6edf79da42f98bb87026,PMC,"Surveillance for respiratory and diarrheal pathogens at the human-pig interface in Sarawak, Malaysia",http://dx.doi.org/10.1371/journal.pone.0201295,PMC6063427,30052648,CC0,"BACKGROUND: The large livestock operations and dense human population of Southeast Asia are considered a hot-spot for emerging viruses. OBJECTIVES: To determine if the pathogens adenovirus (ADV), coronavirus (CoV), encephalomyocarditis virus (EMCV), enterovirus (EV), influenza A-D (IAV, IBV, ICV, and IDV), porcine circovirus 2 (PCV2), and porcine rotaviruses A and C (RVA and RVC), are aerosolized at the animal-interface, and if humans working in these environments are carrying these viruses in their nasal airways. STUDY: This cross-sectional study took place in Sarawak, Malaysia among 11 pig farms, 2 abattoirs, and 3 animal markets in June and July of 2017. Pig feces, pig oral secretions, bioaerosols, and worker nasal wash samples were collected and analyzed via rPCR and rRT-PCR for respiratory and diarrheal viruses. RESULTS: In all, 55 pig fecal, 49 pig oral or water, 45 bioaerosol, and 78 worker nasal wash samples were collected across 16 sites. PCV2 was detected in 21 pig fecal, 43 pig oral or water, 3 bioaerosol, and 4 worker nasal wash samples. In addition, one or more bioaerosol or pig samples were positive for EV, IAV, and RVC, and one or more worker samples were positive for ADV, CoV, IBV, and IDV. CONCLUSIONS: This study demonstrates that nucleic acids from a number of targeted viruses were present in pig oral secretions and pig fecal samples, and that several viruses were detected in bioaerosol samples or in the nasal passages of humans with occupational exposure to pigs. These results demonstrate the need for future research in strengthening viral surveillance at the human-animal interface, specifically through expanded bioaerosol sampling efforts and a seroepidemiological study of individuals with exposure to pigs in this region for PCV2 infection.",2018 Jul 27,"['Borkenhagen, Laura K.', 'Mallinson, Kerry A.', 'Tsao, Rick W.', 'Ha, Siaw-Jing', 'Lim, Wei-Honn', 'Toh, Teck-Hock', 'Anderson, Benjamin D.', 'Fieldhouse, Jane K.', 'Philo, Sarah E.', 'Chong, Kuek-Sen', 'Lindsley, William G.', 'Ramirez, Alejandro', 'Lowe, James F.', 'Coleman, Kristen K.', 'Gray, Gregory C.']",PLoS One,,,True
1919c783b2fb4127114d196eb2b30fcd7a67d15d,PMC,Engineered Protein Model of the ATP synthase H(+)- Channel Shows No Salt Bridge at the Rotor-Stator Interface,http://dx.doi.org/10.1038/s41598-018-29693-z,PMC6063947,30054535,CC BY,"ATP synthase is powered by the flow of protons through the molecular turbine composed of two α-helical integral membrane proteins, subunit a, which makes a stator, and a cylindrical rotor assembly made of multiple copies of subunit c. Transient protonation of a universally conserved carboxylate on subunit c (D61 in E. coli) gated by the electrostatic interaction with arginine on subunit a (R210 in E. coli) is believed to be a crucial step in proton transfer across the membrane. We used a fusion protein consisting of subunit a and the adjacent helices of subunit c to test by NMR spectroscopy if cD61 and aR210 are involved in an electrostatic interaction with each other, and found no evidence of such interaction. We have also determined that R140 does not form a salt bridge with either D44 or D124 as was suggested previously by mutation analysis. Our results demonstrate the potential of using arginines as NMR reporter groups for structural and functional studies of challenging membrane proteins.",2018 Jul 27,"['Pierson, Hannah E.', 'Kaler, Mandeep', 'O’Grady, Christopher', 'Uhlemann, Eva-Maria E.', 'Dmitriev, Oleg Y.']",Sci Rep,,,False
69360aaa87b55456c581620207955ad5fe24223b,PMC,Engineered Protein Model of the ATP synthase H(+)- Channel Shows No Salt Bridge at the Rotor-Stator Interface,http://dx.doi.org/10.1038/s41598-018-29693-z,PMC6063947,30054535,CC BY,"ATP synthase is powered by the flow of protons through the molecular turbine composed of two α-helical integral membrane proteins, subunit a, which makes a stator, and a cylindrical rotor assembly made of multiple copies of subunit c. Transient protonation of a universally conserved carboxylate on subunit c (D61 in E. coli) gated by the electrostatic interaction with arginine on subunit a (R210 in E. coli) is believed to be a crucial step in proton transfer across the membrane. We used a fusion protein consisting of subunit a and the adjacent helices of subunit c to test by NMR spectroscopy if cD61 and aR210 are involved in an electrostatic interaction with each other, and found no evidence of such interaction. We have also determined that R140 does not form a salt bridge with either D44 or D124 as was suggested previously by mutation analysis. Our results demonstrate the potential of using arginines as NMR reporter groups for structural and functional studies of challenging membrane proteins.",2018 Jul 27,"['Pierson, Hannah E.', 'Kaler, Mandeep', 'O’Grady, Christopher', 'Uhlemann, Eva-Maria E.', 'Dmitriev, Oleg Y.']",Sci Rep,,,True
8c9d5b4ab33828757d3e05c4aef238ebbc38a319,PMC,Greater Microbial Translocation and Vulnerability to Metabolic Disease in Healthy Aged Female Monkeys,http://dx.doi.org/10.1038/s41598-018-29473-9,PMC6063974,30054517,CC BY,"Monkeys demonstrate gastrointestinal barrier dysfunction (leaky gut) as evidenced by higher biomarkers of microbial translocation (MT) and inflammation with ageing despite equivalent health status, and lifelong diet and environmental conditions. We evaluated colonic structural, microbiomic and functional changes in old female vervet monkeys (Chlorocebus aethiops sabeus) and how age-related leaky gut alters responses to Western diet. We additionally assessed serum bovine immunoglobulin therapy to lower MT burden. MT was increased in old monkeys despite comparable histological appearance of the ascending colon. Microbiome profiles from 16S sequencing did not show large differences by age grouping, but there was evidence for higher mucosal bacterial loads using qPCR. Innate immune responses were increased in old monkeys consistent with higher MT burdens. Western diet challenge led to elevations in glycemic and hepatic biochemistry values only in old monkeys, and immunoglobulin therapy was not effective in reducing MT markers or improving metabolic health. We interpret these findings to suggest that ageing may lead to lower control over colonization at the mucosal surface, and reduced clearance of pathogens resulting in MT and inflammation. Leaky gut in ageing, which is not readily rescued by innate immune support with immunoglobulin, primes the liver for negative consequences of high fat, high sugar diets.",2018 Jul 27,"['Wilson, Quentin N.', 'Wells, Magan', 'Davis, Ashley T.', 'Sherrill, Christina', 'Tsilimigras, Matthew C. B.', 'Jones, Roshonda B.', 'Fodor, Anthony A.', 'Kavanagh, Kylie']",Sci Rep,,,False
b4c05b7cdc0a9a75d52f42db2151988cc1724194,PMC,Greater Microbial Translocation and Vulnerability to Metabolic Disease in Healthy Aged Female Monkeys,http://dx.doi.org/10.1038/s41598-018-29473-9,PMC6063974,30054517,CC BY,"Monkeys demonstrate gastrointestinal barrier dysfunction (leaky gut) as evidenced by higher biomarkers of microbial translocation (MT) and inflammation with ageing despite equivalent health status, and lifelong diet and environmental conditions. We evaluated colonic structural, microbiomic and functional changes in old female vervet monkeys (Chlorocebus aethiops sabeus) and how age-related leaky gut alters responses to Western diet. We additionally assessed serum bovine immunoglobulin therapy to lower MT burden. MT was increased in old monkeys despite comparable histological appearance of the ascending colon. Microbiome profiles from 16S sequencing did not show large differences by age grouping, but there was evidence for higher mucosal bacterial loads using qPCR. Innate immune responses were increased in old monkeys consistent with higher MT burdens. Western diet challenge led to elevations in glycemic and hepatic biochemistry values only in old monkeys, and immunoglobulin therapy was not effective in reducing MT markers or improving metabolic health. We interpret these findings to suggest that ageing may lead to lower control over colonization at the mucosal surface, and reduced clearance of pathogens resulting in MT and inflammation. Leaky gut in ageing, which is not readily rescued by innate immune support with immunoglobulin, primes the liver for negative consequences of high fat, high sugar diets.",2018 Jul 27,"['Wilson, Quentin N.', 'Wells, Magan', 'Davis, Ashley T.', 'Sherrill, Christina', 'Tsilimigras, Matthew C. B.', 'Jones, Roshonda B.', 'Fodor, Anthony A.', 'Kavanagh, Kylie']",Sci Rep,,,True
4897212ecb3c7d659bda8a992f12f63d3abad13e,PMC,Oral administration of chestnut tannins to reduce the duration of neonatal calf diarrhea,http://dx.doi.org/10.1186/s12917-018-1549-2,PMC6064112,30055618,CC BY,"BACKGROUND: Neonatal calf diarrhea is generally caused by infectious agents and is a very common disease in bovine practice, leading to substantial economic losses. Tannins are known for their astringent and anti-inflammatory properties in the gastro-enteric tract. The aim of this study was to evaluate the effect of the oral administration of chestnut tannins (Castanea sativa Mill.) in order to reduce the duration of calf neonatal diarrhea. Twenty-four Italian Friesian calves affected by neonatal diarrhea were included. The duration of the diarrheic episode (DDE) was recorded and the animals were divided into a control group (C), which received Effydral® in 2 l of warm water, and a tannin-treated group (T), which received Effydral® in 2 l of warm water plus 10 g of extract of chestnut tannins powder. A Mann-Whitney test was performed to verify differences for the DDE values between the two groups. RESULTS: The DDE was significantly higher in group C than in group T (p = 0.02), resulting in 10.1 ± 3.2 and 6.6 ± 3.8 days, respectively. CONCLUSIONS: Phytotherapic treatments for various diseases have become more common both in human and in veterinary medicine, in order to reduce the presence of antibiotic molecules in the food chain and in the environment. Administration of tannins in calves with diarrhea seemed to shorten the DDE in T by almost 4 days compared to C, suggesting an effective astringent action of chestnut tannins in the calf, as already reported in humans. The use of chestnut tannins in calves could represent an effective, low-impact treatment for neonatal diarrhea.",2018 Jul 28,"['Bonelli, F.', 'Turini, L.', 'Sarri, G.', 'Serra, A.', 'Buccioni, A.', 'Mele, M.']",BMC Vet Res,,,True
d6d9d71d7a16885f268b86b5b8291bffa869ce43,PMC,Antibacterial activity evaluation of selected essential oils in liquid and vapor phase on respiratory tract pathogens,http://dx.doi.org/10.1186/s12906-018-2291-9,PMC6064118,30053847,CC BY,"BACKGROUND: The increasing number of multidrug-resistant bacteria and the fact of antibiotic resistance is leading to a continuous need for discovering alternative treatments against infections, e.g. in the case of respiratory tract diseases. Essential oils (EOs), because of their volatility, can easily reach both the upper and lower parts of the respiratory tract via inhalation. Therefore, the aim of the present study was the antibacterial evaluation of clove, cinnamon bark, eucalyptus, thyme, scots pine, peppermint, and citronella EOs against respiratory tract pathogens such as Streptococcus pneumoniae, S. mutans, S. pyogenes, Haemophilus influenzae, H. parainfluenzae, and Moraxella catarrhalis. Furthermore, we wanted to compare the antibacterial effect of these EOs in two different test systems to provide data for the development of an appropriate product formulation. METHODS: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined with in vitro vapor phase test (VPT) and broth macrodilution test (BDT). The chemical and percentage compositions of the EOs were determined by GC-MS and GC-FID analysis. RESULTS: Among the EOs, thyme was the most effective against S. mutans (MIC: 0.04 mg/mL in BDT, but cinnamon bark and clove oils also presented high inhibition in liquid medium with MIC values of 0.06 mg/mL and 0.1 mg/mL against S. pneumoniae and S. pyogenes, respectively. M. catarrhalis was the most sensitive to thyme EO (MIC: 0.09 mg/mL). Cinnamon bark EO was the most effective against Haemophilus spp. (MIC: 0.06 mg/mL). In the VPT, cinnamon bark was the most effective oil against all investigated pathogens with MIC values in the range of 15.62–90 μl/L. Surprisingly, the eucalyptus and scots pine showed weak activity against the test bacteria in both test systems. CONCLUSIONS: The EO of thyme, clove and cinnamon bark may provide promising antibacterial activity against respiratory tract pathogens either in liquid medium or in vapor phase. However, their effect is lower than that of the reference antibiotics. The combination of EOs and antibiotics may be beneficial in the alternative treatment of respiratory tract diseases. In vivo studies are necessary to calculate the effective dose of EOs in patients and determine their possible side effects and toxicity.",2018 Jul 27,"['Ács, Kamilla', 'Balázs, Viktória L.', 'Kocsis, Béla', 'Bencsik, Tímea', 'Böszörményi, Andrea', 'Horváth, Györgyi']",BMC Complement Altern Med,,,True
1c5b9b791b402f44f6229f9d420d6a10dc173d39,PMC,A network pharmacology-based approach to analyse potential targets of traditional herbal formulas: An example of Yu Ping Feng decoction,http://dx.doi.org/10.1038/s41598-018-29764-1,PMC6065326,30061691,CC BY,"Herbal formulas from traditional Chinese medicines (TCMs) have been extensively used in clinics as effective therapies, but it is still a great challenge to demonstrate the scientific basis for their therapeutic effects at the level of molecular biology. By taking a classic herbal formula (Yu Ping Feng decoction, YPF) as an example, this study developed a novel network pharmacology based method to identify its potential therapeutic targets. First, this study constructed a “targets–(pathways)–targets” (TPT) network in which targets of YPF were connected by relevant pathways; then, this network was decomposed into separate modules with strong internal connections; lastly, the propensity of each module toward different diseases was assessed by a contribution score. On the basis of a significant association between network modules and therapeutic diseases validated by chi-square test (p-value < 0.001), this study identified the network module with the strongest propensity toward therapeutic diseases of YPF. Further, the targets with the highest centrality in this module are recommended as YPF’s potential therapeutic targets. By integrating the complicated “multi-targets–multi-pathways–multi-diseases” relationship of herbal formulas, the method shows promise for identifying its potential therapeutic targets, which could contribute to the modern scientific illustration of TCMs’ traditional clinical applications.",2018 Jul 30,"['Zuo, Huali', 'Zhang, Qianru', 'Su, Shibing', 'Chen, Qilong', 'Yang, Fengqing', 'Hu, Yuanjia']",Sci Rep,,,True
2906d781d6cac5a07bf2826f620a788e3f8432ef,PMC,Oral edible plant vaccine containing hypoallergen of American cockroach major allergen Per a 2 prevents roach-allergic asthma in a murine model,http://dx.doi.org/10.1371/journal.pone.0201281,PMC6066233,30059516,CC BY,"BACKGROUND: American cockroaches (Periplaneta americana) are an important indoor allergen source and a major risk factor for exacerbations and poor control of asthma. We previously reported that allergen components from American cockroaches exhibit varying levels of pathogenicity. Sensitization to major American cockroach allergen, Per a 2, correlated with more severe clinical phenotypes among patients with allergic airway diseases. MATERIALS AND METHODS: In this study, we examined whether oral plant vaccine-encoding full-length Per a 2 clone-996 or its hypoallergenic clone-372 could exert a prophylactic role in Per a 2-sensitized mice. The cDNAs coding Per a 2–996 and Per a 2–372 were inserted into TuMV vector and expressed in Chinese cabbage. Adult female BALB/c mice were fed with the cabbage extracts for 21 days and subsequently underwent two-step sensitization with recombinant Per a 2. RESULTS: Per a 2-specific IgE measured by in-house ELISA in the sera of Per a 2-372-treated groups were significantly lower than in the control groups after allergen challenge but not the Per a 2-996-treated group. Moreover, Per a 2–372 vaccine markedly decreased airway hyper-responsiveness and infiltration of inflammatory cells into the lungs, as well as reduced mRNA expression of IL-4 and IL-13 in comparison with the control mice. CONCLUSION: Our data suggest that oral administration of edible plant vaccine encoding Per a 2 hypo-allergen may be used as a prophylactic strategy against the development of cockroach allergy.",2018 Jul 30,"['Lee, Mey-Fann', 'Chiang, Chu-Hui', 'Li, Ying-Lan', 'Wang, Nancy M.', 'Song, Pei-Pong', 'Lin, Shyh-Jye', 'Chen, Yi-Hsing']",PLoS One,,,True
39809942de9e0dd4d8449754015aa6f9aec3e2c1,PMC,"Severe Acute Respiratory Infection (SARI) sentinel surveillance in the country of Georgia, 2015-2017",http://dx.doi.org/10.1371/journal.pone.0201497,PMC6066249,30059540,CC BY,"BACKGROUND: Severe Acute Respiratory Infection (SARI) causes substantial mortality and morbidity worldwide. The country of Georgia conducts sentinel surveillance to monitor SARI activity and changes in its infectious etiology. This study characterizes the epidemiology of SARI in Georgia over the 2015/16 and 2016/17 influenza seasons, compares clinical presentations by etiology, and estimates influenza vaccine effectiveness using a test-negative design. METHODS: SARI cases were selected through alternate day systematic sampling between September 2015 and March 2017 at five sentinel surveillance inpatient sites. Nasopharyngeal swabs were tested for respiratory viruses and Mycoplasma pneumoniae using a multiplex diagnostic system. We present SARI case frequencies by demographic characteristics, co-morbidities, and clinical presentation, and used logistic regression to estimate influenza A vaccine effectiveness. RESULTS: 1,624 patients with SARI were identified. More cases occurred in February (28.7%; 466/1624) than other months. Influenza was the dominant pathogen in December-February, respiratory syncytial virus in March-May, and rhinovirus in June-November. Serious clinical symptoms including breathing difficulties, ICU hospitalization, and artificial ventilation were common among influenza A and human metapneumovirus cases. For influenza A/H3, a protective association between vaccination and disease status was observed when cases with unknown vaccination status were combined with those who were unvaccinated (OR: 0.53, 95% CI: 0.30, 0.97). CONCLUSIONS: Multi-pathogen diagnostic testing through Georgia’s sentinel surveillance provides useful information on etiology, seasonality, and demographic associations. Influenza A and B were associated with more severe outcomes, although the majority of the population studied was unvaccinated. Findings from sentinel surveillance can assist in prevention planning.",2018 Jul 30,"['Chakhunashvili, Giorgi', 'Wagner, Abram L.', 'Power, Laura E.', 'Janusz, Cara B.', 'Machablishvili, Ann', 'Karseladze, Irakli', 'Tarkhan-Mouravi, Olgha', 'Zakhashvili, Khatuna', 'Imnadze, Paata', 'Gray, Gregory C.', 'Anderson, Benjamin', 'Boulton, Matthew L.']",PLoS One,,,True
3285bc7a5f35e4f198ce1517d61bb00f5fe0abce,PMC,Technoeconomic Modeling of Plant-Based Griffithsin Manufacturing,http://dx.doi.org/10.3389/fbioe.2018.00102,PMC6066545,30087892,CC BY,"Griffithsin is a marine algal lectin that exhibits broad-spectrum antiviral activity by binding oligomannose glycans on viral envelope glycoproteins, including those found in HIV-1, HSV-2, SARS, HCV and other enveloped viruses. An efficient, scalable and cost-effective manufacturing process for Griffithsin is essential for the adoption of this drug in human antiviral prophylaxis and therapy, particularly in cost-sensitive indications such as topical microbicides for HIV-1 prevention. The production of certain classes of recombinant biologics in plants can offer scalability, cost and environmental impact advantages over traditional biomanufacturing platforms. Previously, we showed the technical viability of producing recombinant Griffithsin in plants. In this study, we conducted a technoeconomic analysis (TEA) of plant-produced Griffithsin manufactured at commercial launch volumes for use in HIV microbicides. Data derived from multiple non-sequential manufacturing batches conducted at pilot scale and existing facility designs were used to build a technoeconomic model using SuperPro Designer(®) modeling software. With an assumed commercial launch volume of 20 kg Griffithsin/year for 6.7 million doses of Griffithsin microbicide at 3 mg/dose, a transient vector expression yield of 0.52 g Griffithsin/kg leaf biomass, recovery efficiency of 70%, and purity of >99%, we calculated a manufacturing cost for the drug substance of $0.32/dose and estimated a bulk product cost of $0.38/dose assuming a 20% net fee for a contract manufacturing organization (CMO). This is the first report modeling the manufacturing economics of Griffithsin. The process analyzed is readily scalable and subject to efficiency improvements and could provide the needed market volumes of the lectin within an acceptable range of costs, even for cost-constrained products such as microbicides. The manufacturing process was also assessed for environmental, health and safety impact and found to have a highly favorable environmental output index with negligible risks to health and safety. The results of this study help validate the plant-based manufacturing platform and should assist in selecting preferred indications for Griffithsin as a novel drug.",2018 Jul 24,"['Alam, Aatif', 'Jiang, Linda', 'Kittleson, Gregory A.', 'Steadman, Kenneth D.', 'Nandi, Somen', 'Fuqua, Joshua L.', 'Palmer, Kenneth E.', 'Tusé, Daniel', 'McDonald, Karen A.']",Front Bioeng Biotechnol,,,False
f909ff3d201ad4ddc44488137db54eb2a4be076e,PMC,Technoeconomic Modeling of Plant-Based Griffithsin Manufacturing,http://dx.doi.org/10.3389/fbioe.2018.00102,PMC6066545,30087892,CC BY,"Griffithsin is a marine algal lectin that exhibits broad-spectrum antiviral activity by binding oligomannose glycans on viral envelope glycoproteins, including those found in HIV-1, HSV-2, SARS, HCV and other enveloped viruses. An efficient, scalable and cost-effective manufacturing process for Griffithsin is essential for the adoption of this drug in human antiviral prophylaxis and therapy, particularly in cost-sensitive indications such as topical microbicides for HIV-1 prevention. The production of certain classes of recombinant biologics in plants can offer scalability, cost and environmental impact advantages over traditional biomanufacturing platforms. Previously, we showed the technical viability of producing recombinant Griffithsin in plants. In this study, we conducted a technoeconomic analysis (TEA) of plant-produced Griffithsin manufactured at commercial launch volumes for use in HIV microbicides. Data derived from multiple non-sequential manufacturing batches conducted at pilot scale and existing facility designs were used to build a technoeconomic model using SuperPro Designer(®) modeling software. With an assumed commercial launch volume of 20 kg Griffithsin/year for 6.7 million doses of Griffithsin microbicide at 3 mg/dose, a transient vector expression yield of 0.52 g Griffithsin/kg leaf biomass, recovery efficiency of 70%, and purity of >99%, we calculated a manufacturing cost for the drug substance of $0.32/dose and estimated a bulk product cost of $0.38/dose assuming a 20% net fee for a contract manufacturing organization (CMO). This is the first report modeling the manufacturing economics of Griffithsin. The process analyzed is readily scalable and subject to efficiency improvements and could provide the needed market volumes of the lectin within an acceptable range of costs, even for cost-constrained products such as microbicides. The manufacturing process was also assessed for environmental, health and safety impact and found to have a highly favorable environmental output index with negligible risks to health and safety. The results of this study help validate the plant-based manufacturing platform and should assist in selecting preferred indications for Griffithsin as a novel drug.",2018 Jul 24,"['Alam, Aatif', 'Jiang, Linda', 'Kittleson, Gregory A.', 'Steadman, Kenneth D.', 'Nandi, Somen', 'Fuqua, Joshua L.', 'Palmer, Kenneth E.', 'Tusé, Daniel', 'McDonald, Karen A.']",Front Bioeng Biotechnol,,,True
99e6b617ea3f4d122410160e631c4021e6a8969c,PMC,Influenza Vaccination in Type 2 Diabetes Patients: Coverage Status and Its Determinants in Southwestern Saudi Arabia,http://dx.doi.org/10.3390/ijerph15071381,PMC6068768,29966382,CC BY,"Despite the significant role of seasonal influenza vaccination in preventing and minimizing the serious complications of influenza infection in type 2 diabetes mellitus (T2DM) patients, unsatisfactory compliance still exists for vaccination. Study objectives were to explore the vaccination status and determinants in T2DM patients in southwestern Saudi Arabia. A cross-sectional study on a representative sample of T2DM patients in Abha city, southwestern Saudi Arabia, was conducted. Data for sociodemographic characteristics, clinical criteria, vaccination status, vaccination motivators and barriers and seasonal influenza knowledge were collected. Out of 353 T2DM patients included in the study, seasonal influenza vaccination coverage was 61% in year 2017. A significant factors associated with non-vaccination were; poor influenza and its vaccine knowledge (OR = 4.31, 95% CI: 2.73–6.80), illiteracy (OR = 1.93, 95% CI: 1.11–3.37), and more than 10 years disease duration (OR = 2.07, 95% CI: 1.11–3.87). Presence of family history of DM and ischemic heart comorbidity minimized the possibility of non-vaccination (OR = 0.54 and 0.28 respectively). Healthcare givers’ advice was the most reported vaccination motivator (84.7%) while; fear of vaccine side effects was the most stated barrier (73%). In conclusion, influenza vaccination rate among T2DM in the present study is less than the recommended level. Continuous primary health care center-based educational programs should be implemented to aware and encourage influenza vaccination among T2DM patients.",2018 Jul 1,"['Alnaheelah, Ibraheem M.', 'Awadalla, Nabil J.', 'Al-Musa, Khalid M.', 'Alsabaani, Abdullah A.', 'Mahfouz, Ahmed A.']",Int J Environ Res Public Health,,,True
75c2dba50049d4ee01ac711d152c62b018f31cf9,PMC,Reverse Genetics for Type I Feline Coronavirus Field Isolate To Study the Molecular Pathogenesis of Feline Infectious Peritonitis,http://dx.doi.org/10.1128/mBio.01422-18,PMC6069117,30065095,CC BY,"Feline infectious peritonitis (FIP), one of the most important lethal infections of cats, is caused by feline infectious peritonitis virus (FIPV), the high-virulence biotype of feline coronaviruses (FCoVs). FIPVs are suggested to emerge from feline enteric coronaviruses (FECVs) by acquiring mutations in specific genes in the course of persistent infections. Although numerous studies identified mutations predicted to be responsible for the FECV-FIPV biotype switch, the presumed roles of specific genetic changes in FIP pathogenesis have not been confirmed experimentally. Reverse genetics systems established previously for serotype I and the less common serotype II FCoVs were based on cell culture-adapted FIPV strains which, however, were shown to be unsuitable for FIP pathogenesis studies in vivo. To date, systems to produce and manipulate recombinant serotype I field viruses have not been developed, mainly because these viruses cannot be grown in vitro. Here, we report the first reverse genetics system based on a serotype I FECV field isolate that is suitable to produce high-titer stocks of recombinant FECVs. We demonstrate that these recombinant viruses cause productive persistent infections in cats that are similar to what is observed in natural infections. The system provides an excellent tool for studying FCoVs that do not grow in standard cell culture systems and will greatly facilitate studies into the molecular pathogenesis of FIP. Importantly, the system could also be adapted for studies of other RNA viruses with large genomes whose production and characterization in vivo are currently hampered by the lack of in vitro propagation systems.",2018 Jul 31,"['Ehmann, Rosina', 'Kristen-Burmann, Claudia', 'Bank-Wolf, Barbara', 'König, Matthias', 'Herden, Christiane', 'Hain, Torsten', 'Thiel, Heinz-Jürgen', 'Ziebuhr, John', 'Tekes, Gergely']",mBio,,,True
fbaaee7a5ac9ab3324e82bc7b8706edc5bd1524e,PMC,Immunization by Replication-Competent Controlled Herpesvirus Vectors,http://dx.doi.org/10.1128/JVI.00616-18,PMC6069180,29899091,CC BY,"Replication-competent controlled virus vectors were derived from the virulent herpes simplex virus 1 (HSV-1) wild-type strain 17syn+ by placing one or two replication-essential genes under the stringent control of a gene switch that is coactivated by heat and an antiprogestin. Upon activation of the gene switch, the vectors replicate in infected cells with an efficacy that approaches that of the wild-type virus from which they were derived. Essentially no replication occurs in the absence of activation. When administered to mice, localized application of a transient heat treatment in the presence of systemic antiprogestin results in efficient but limited virus replication at the site of administration. The immunogenicity of these viral vectors was tested in a mouse footpad lethal challenge model. Unactivated viral vectors—which may be regarded as equivalents of inactivated vaccines—induced detectable protection against lethality caused by wild-type virus challenge. Single activation of the viral vectors at the site of administration (rear footpads) greatly enhanced protective immune responses, and a second immunization resulted in complete protection. Once activated, vectors also induced far better neutralizing antibody and HSV-1-specific cellular immune responses than unactivated vectors. To find out whether the immunogenicity of a heterologous antigen was also enhanced in the context of efficient transient vector replication, a virus vector constitutively expressing an equine influenza virus hemagglutinin was constructed. Immunization of mice with this recombinant induced detectable antibody-mediated neutralization of equine influenza virus, as well as a hemagglutinin-specific cellular immune response. Single activation of viral replication resulted in a severalfold enhancement of these immune responses. IMPORTANCE We hypothesized that vigorous replication of a pathogen may be critical for eliciting the most potent and balanced immune response against it. Hence, attenuation/inactivation (as in conventional vaccines) should be avoided. Instead, the necessary safety should be provided by placing replication of the pathogen under stringent control and by activating time-limited replication of the pathogen strictly in an administration region in which pathology cannot develop. Immunization will then occur in the context of highly efficient pathogen replication and uncompromised safety. We found that localized activation in mice of efficient but limited replication of a replication-competent controlled herpesvirus vector resulted in a greatly enhanced immune response to the virus or an expressed heterologous antigen. This finding supports the above-mentioned hypothesis and suggests that the vectors may be promising novel agents worth exploring for the prevention/mitigation of infectious diseases for which efficient vaccination is lacking, in particular in immunocompromised patients.",2018 Jul 31,"['Bloom, David C.', 'Tran, Robert K.', 'Feller, Joyce', 'Voellmy, Richard']",J Virol,,,True
9ae5509495e79b5d077ce582f092950b38982dfa,PMC,Mapping Oil Spills from Dual-Polarized SAR Images Using an Artificial Neural Network: Application to Oil Spill in the Kerch Strait in November 2007,http://dx.doi.org/10.3390/s18072237,PMC6069476,29997367,CC BY,"Synthetic aperture radar (SAR) has been widely used to detect oil-spill areas through the backscattering intensity difference between oil and background pixels. However, since the signal is similar to that produced by other phenomena, positive identification can be challenging. In this study we developed an algorithm to effectively analyze large-scale oil spill areas in SAR images by focusing on optimizing the input layer to artificial neural network (ANN) through removal the factor of lowering the accuracy. An ANN algorithm was used to generate probability maps of oil spills. Highly accurate pixel-based data processing was conducted through false or un-detection element reduction by normalizing the image or applying a non-local (NL) means filter and median filter to the input neurons for ANN. In addition, the standard deviation of co-polarized phase difference (CPD) was used to reduce false detection from the look-alike with weak damping effect. The algorithm was validated using TerraSAR-X images of an oil spill caused by stranded oil tanker Volganefti-139 in the Kerch Strait in 2007. According to the validation results of the receiver operating characteristic (ROC) curve, the oil spill was detected with an accuracy of about 95.19% and un-detection or false detection by look-alike and speckle noise was greatly reduced.",2018 Jul 11,"['Kim, Daeseong', 'Jung, Hyung-Sup']",Sensors (Basel),,,True
e31625f324f8a44bca6c701f2c6e6d7c09a0830c,PMC,"Molecular detection of Enteropathogens from diarrheic stool of HIV positive patients in Gondar, Ethiopia",http://dx.doi.org/10.1186/s12879-018-3265-8,PMC6069753,30064366,CC BY,"BACKGROUND: Infectious diarrhea is a common problem in the developing world, especially among people living with HIV/AIDS. Traditional diagnostic methods such as stool culture and microscopic examination are limited by resources and poor sensitivity. The use of molecular diagnostics for enteropathogen detection in this region of sub-Saharan Africa has not been fully explored. We sought to identify risk factors and characterize enteropathogens from diarrheic stools of HIV-positive patients in Gondar, Ethiopia using multiplex molecular panels targeting key infectious agents. METHODS: A cross-sectional study of 100 stool samples was performed. Samples were collected consecutively from HIV- positive patients presenting with diarrhea at University of Gondar Hospital clinic, a major center in NW Ethiopia. Genomic DNA was extracted from stool and processed using a multiplex molecular panel Allplex™ [Seegene, Canada]. Correlations between patient characteristics, symptoms, public health risk factors, and enteropathogen type (s) were studied. Eighty-six samples were successfully analyzed by molecular methods. RESULTS: The mean age was 35 with 43% male. Eighty percent lived in an urban area, 18% had access to well water only, and 81% practiced proper hand hygiene. The majority of patients (72%) were receiving HAART with a median CD4 cell count of 362/μL. Multiple pathogens were detected in 94% of specimens, with an average of 5 enteropathogens per sample. Common bacteria, viruses, and parasites detected were Shigella spp./enteroinvasive E. coli (80%), enterotoxigenic E. coli (73%), Norovirus (16%) and B. hominis (62%). CD4 cell count < 500/ μL was associated with the presence of viruses (p = 0.004) and the absence of STEC (p = 0.010). The use of HAART or CD4 levels was not associated with the number of enteropathogens detected. CONCLUSIONS: Diarrheic stool from HIV-positive outpatients in Gondar, Ethiopia had on average 5 enteropathogens present in their stool. Shigellaspp./enteroinvasive E. coli and enterotoxigenic E. coli are the major pathogens, not dissimilar to immunocompetent individuals in low income countries.",2018 Jul 31,"['Seid, Lubaba', 'Stokes, William', 'Bayih, Abebe Genetu', 'Getie, Sisay', 'Abere, Aberham', 'Tesfa, Habtie', 'Pillai, Dylan R.']",BMC Infect Dis,,,True
412aab9232d9b674c8ba7519a3c85ae72c2f0b9e,PMC,Inhibition of enterovirus 71 replication and viral 3C protease by quercetin,http://dx.doi.org/10.1186/s12985-018-1023-6,PMC6069798,30064445,CC BY,"BACKGROUND: Enterovirus 71 (EV71) is one of the major causative agents of hand, foot, and mouth disease (HFMD), which is sometimes associated with severe central nervous system disease in children. There is currently no specific medication for EV71 infection. Quercetin, one of the most widely distributed flavonoids in plants, has been demonstrated to inhibit various viral infections. However, investigation of the anti-EV71 mechanism has not been reported to date. METHODS: The anti-EV71 activity of quercetin was evaluated by phenotype screening, determining the cytopathic effect (CPE) and EV71-induced cells apoptosis. The effects on EV71 replication were evaluated further by determining virus yield, viral RNA synthesis and protein expression, respectively. The mechanism of action against EV71 was determined from the effective stage and time-of-addition assays. The possible inhibitory functions of quercetin via viral 2Apro, 3C(pro) or 3D(pol) were tested. The interaction between EV71 3C(pro) and quercetin was predicted and calculated by molecular docking. RESULTS: Quercetin inhibited EV71-mediated cytopathogenic effects, reduced EV71 progeny yields, and prevented EV71-induced apoptosis with low cytotoxicity. Investigation of the underlying mechanism of action revealed that quercetin exhibited a preventive effect against EV71 infection and inhibited viral adsorption. Moreover, quercetin mediated its powerful therapeutic effects primarily by blocking the early post-attachment stage of viral infection. Further experiments demonstrated that quercetin potently inhibited the activity of the EV71 protease, 3C(pro), blocking viral replication, but not the activity of the protease, 2A(pro), or the RNA polymerase, 3D(pol). Modeling of the molecular binding of the 3C(pro)-quercetin complex revealed that quercetin was predicted to insert into the substrate-binding pocket of EV71 3C(pro), blocking substrate recognition and thereby inhibiting EV71 3C(pro) activity. CONCLUSIONS: Quercetin can effectively prevent EV71-induced cell injury with low toxicity to host cells. Quercetin may act in more than one way to deter viral infection, exhibiting some preventive and a powerful therapeutic effect against EV71. Further, quercetin potently inhibits EV71 3C(pro) activity, thereby blocking EV71 replication.",2018 Jul 31,"['Yao, Chenguang', 'Xi, Caili', 'Hu, Kanghong', 'Gao, Wa', 'Cai, Xiaofeng', 'Qin, Jinlan', 'Lv, Shiyun', 'Du, Canghao', 'Wei, Yanhong']",Virol J,,,True
5fe161cec1e62818c325d515ec8a2a93af178cfd,PMC,Establishment and optimization of a liquid bead array for the simultaneous detection of ten insect-borne pathogens,http://dx.doi.org/10.1186/s13071-018-2996-0,PMC6069843,30064470,CC BY,"BACKGROUND: Insect-borne diseases could induce severe symptoms in human and clinical signs in animals, such as febrility, erythra, arthralgia and hemorrhagic fever, and cause significant economic losses and pose public health threat all over the world. The significant advantages of Luminex xMAP technology are high-throughput, high parallel and automation. This study aimed to establish a liquid bead array based on Luminex xMAP technology that was able to simultaneously detect multiple insect-borne pathogens. METHODS: Specific probes and primers to detect the nucleic acid of 10 insect-borne pathogens were designed. Probes were coupled with fluorescent carboxylated microspheres. The parameters of the system were optimized, including ratio of forward/reverse primers (1:2), hybridization temperature (50 °C) and duration (30 min) and quantity of PCR product (2 μl). The sensitivity and specificity of the system were also evaluated. Moreover mixed nucleic acid of 10 insect-borne pathogens, including Bluetongue virus, Epizootic hemorrhagic disease virus of deer, Coxiella burnetii, African swine fever virus, West Nile fever virus, Borrelia burgdorferi, vesicular stomatitis virus, Rift Valley fever virus, Ebola virus and Schmalenberg’s disease virus, and 3000 clinical samples were tested for practicability. RESULTS: The optimized detection system showed high sensitivity, specificity and reproducibility. Each probe showed specific fluorescence signal intensity without any cross-hybridization for the other insect-borne pathogens tested, which included dengue virus, tick-borne encephalitis virus, Japanese encephalitis virus, Xinjiang hemorrhagic fever virus, spotted fever group rickettsiae, ehrlichiae and chikungunya virus. The limit of detection was 10 copies of target gene. Insect-borne pathogens were successfully detected among the 3000 clinical samples, and the results were consistent with those obtained using gold-standard assays or commercial nucleic acid detection kits. CONCLUSIONS: This optimized liquid array detection system was high-throughput and highly specific and sensitive in screening of the insect-borne pathogens. It was promising in detection of these pathogens for molecular epidemiological studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-018-2996-0) contains supplementary material, which is available to authorized users.",2018 Jul 31,"['Wang, Hui-yu', 'Wu, Shao-qiang', 'Jiang, Li', 'Xiao, Rong-hai', 'Li, Ting', 'Mei, Lin', 'Lv, Ji-zhou', 'Liu, Jia-jia', 'Lin, Xiang-mei', 'Han, Xue-qing']",Parasit Vectors,,,True
cda16c8657cf582952bfe3a8e6756acaa8449452,PMC,Characterisation of the Virome of Tonsils from Conventional Pigs and from Specific Pathogen-Free Pigs,http://dx.doi.org/10.3390/v10070382,PMC6071052,30036964,CC BY,"Porcine respiratory disease is a multifactorial disease that can be influenced by a number of different microorganisms, as well as by non-infectious factors such as the management and environment of the animals. It is generally believed that the interaction between different infectious agents plays an important role in regard to respiratory diseases. Therefore, we used high-throughput sequencing combined with viral metagenomics to characterise the viral community of tonsil samples from pigs coming from a conventional herd with lesions in the respiratory tract at slaughter. In parallel, samples from specific pathogen-free pigs were also analysed. This study showed a variable co-infection rate in the different pigs. The differences were not seen at the group level but in individual pigs. Some viruses such as adenoviruses and certain picornaviruses could be found in most pigs, while others such as different parvoviruses and anelloviruses were only identified in a few pigs. In addition, the complete coding region of porcine parvovirus 7 was obtained, as were the complete genomes of two teschoviruses. The results from this study will aid in elucidating which viruses are circulating in both healthy pigs and in pigs associated with respiratory illness. This knowledge is needed for future investigations into the role of viral-viral interactions in relation to disease development.",2018 Jul 20,"['Blomström, Anne-Lie', 'Ye, Xingyu', 'Fossum, Caroline', 'Wallgren, Per', 'Berg, Mikael']",Viruses,,,True
1673be3a6c0cd5762dcdabc21816f4acdc102e31,PMC,Display of Porcine Epidemic Diarrhea Virus Spike Protein on Baculovirus to Improve Immunogenicity and Protective Efficacy,http://dx.doi.org/10.3390/v10070346,PMC6071207,29954081,CC BY,"A new variant of the porcine epidemic diarrhea virus (PEDV) is an emerging swine disease, killing considerable numbers of neonatal piglets in North America and Asia in recent years. To generate immunogens mimicking the complex spike (S) protein folding with proper posttranslational modification to mount a robust immune response against the highly virulent PEDV, two baculoviruses displaying the full-length S protein (S-Bac) and the S1 protein (S1-Bac) of the virulent Taiwan genotype 2b (G2b) PEDV Pintung 52 (PEDV-PT) strain were constructed. Intramuscular immunizations of mice and piglets with the S-Bac and S1-Bac demonstrated significantly higher levels of systemic anti-PEDV S-specific IgG, as compared with control group. Our results also showed that piglets in the S-Bac group elicited superior PEDV-specific neutralizing antibodies than those of the S1-Bac and control groups. The highly virulent PEDV-PT strain challenge experiment showed that piglets immunized with S-Bac and S1-Bac showed milder clinical symptoms with significantly less fecal viral shedding as compared with non-immunized control piglets. More importantly, piglets immunized with the S-Bac exhibited no to mild clinical signs, with a delayed, minimal viral shedding. Our results demonstrated that the S-Bac could serve as a safe, easy to manipulate, and effective vaccine candidate against the PEDV infection.",2018 Jun 27,"['Chang, Chia-Yu', 'Hsu, Wei-Ting', 'Chao, Yu-Chan', 'Chang, Hui-Wen']",Viruses,,,True
86ba599c91bdbd03345c42fab209766f19f3c5dc,PMC,Tick-Borne Flaviviruses and the Type I Interferon Response,http://dx.doi.org/10.3390/v10070340,PMC6071234,29933625,CC BY,"Flaviviruses are globally distributed pathogens causing millions of human infections every year. Flaviviruses are arthropod-borne viruses and are mainly transmitted by either ticks or mosquitoes. Mosquito-borne flaviviruses and their interactions with the innate immune response have been well-studied and reviewed extensively, thus this review will discuss tick-borne flaviviruses and their interactions with the host innate immune response.",2018 Jun 21,"['Lindqvist, Richard', 'Upadhyay, Arunkumar', 'Överby, Anna K.']",Viruses,,,True
7f923809d6875b38e21636801b4a50f8fbac6aef,PMC,Protection against Virulent Infectious Bronchitis Virus Challenge Conferred by a Recombinant Baculovirus Co-Expressing S1 and N Proteins,http://dx.doi.org/10.3390/v10070347,PMC6071288,29954092,CC BY,"Avian infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis, which results in considerable economic losses. It is imperative to develop safe and efficient candidate vaccines to control IBV infection. In the current study, recombinant baculoviruses co-expressing the S1 and N proteins and mono-expressing S1 or N proteins of the GX-YL5 strain of IBV were constructed and prepared into subunit vaccines rHBM-S1-N, rHBM-S1 and rHBM-N. The levels of immune protection of these subunit vaccines were evaluated by inoculating specific pathogen-free (SPF) chickens at 14 days of age, giving them a booster with the same dose 14 days later and challenging them with a virulent GX-YL5 strain of IBV 14 days post-booster (dpb). The commercial vaccine strain H120 was used as a control. The IBV-specific antibody levels, as well as the percentages of CD4+ and CD8+ T lymphocytes, were detected within 28 days post-vaccination (dpv). The morbidity, mortality and re-isolation of the virus from the tracheas and kidneys of challenged birds were evaluated at five days post-challenge (dpc). The results showed that the IBV-specific antibody levels and the percentages of CD4+ and CD8+ T lymphocytes were higher in the rHBM-S1-N vaccinated birds compared to birds vaccinated with the rHBM-S1 and rHBM-N vaccines. At 5 dpc, the mortality, morbidity and virus re-isolation rate of the birds vaccinated with the rHBM-S1-N vaccine were slightly higher than those vaccinated with the H120 control vaccine but were lower than those vaccinated with the rHBM-S1 and rHBM-N vaccines. The present study demonstrated that the protection of the recombinant baculovirus co-expressing S1 and N proteins was better than that of recombinant baculoviruses mono-expressing the S1 or N protein. Thus, the recombinant baculovirus co-expressing S1 and N proteins could serve as a potential IBV vaccine and this demonstrates that the bivalent subunit vaccine including the S1 and N proteins might be a strategy for the development of an IBV subunit vaccine.",2018 Jun 27,"['Yuan, Yuan', 'Zhang, Zhi-Peng', 'He, Yi-Ning', 'Fan, Wen-Sheng', 'Dong, Zhi-Hua', 'Zhang, Li-Hua', 'Sun, Xin-Kuan', 'Song, Li-Li', 'Wei, Tian-Chao', 'Mo, Mei-Lan', 'Wei, Ping']",Viruses,,,True
7c04dddb0ce909c5cdec7db6b6333988a9c4196e,PMC,Protection against Virulent Infectious Bronchitis Virus Challenge Conferred by a Recombinant Baculovirus Co-Expressing S1 and N Proteins,http://dx.doi.org/10.3390/v10070347,PMC6071288,29954092,CC BY,"Avian infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis, which results in considerable economic losses. It is imperative to develop safe and efficient candidate vaccines to control IBV infection. In the current study, recombinant baculoviruses co-expressing the S1 and N proteins and mono-expressing S1 or N proteins of the GX-YL5 strain of IBV were constructed and prepared into subunit vaccines rHBM-S1-N, rHBM-S1 and rHBM-N. The levels of immune protection of these subunit vaccines were evaluated by inoculating specific pathogen-free (SPF) chickens at 14 days of age, giving them a booster with the same dose 14 days later and challenging them with a virulent GX-YL5 strain of IBV 14 days post-booster (dpb). The commercial vaccine strain H120 was used as a control. The IBV-specific antibody levels, as well as the percentages of CD4+ and CD8+ T lymphocytes, were detected within 28 days post-vaccination (dpv). The morbidity, mortality and re-isolation of the virus from the tracheas and kidneys of challenged birds were evaluated at five days post-challenge (dpc). The results showed that the IBV-specific antibody levels and the percentages of CD4+ and CD8+ T lymphocytes were higher in the rHBM-S1-N vaccinated birds compared to birds vaccinated with the rHBM-S1 and rHBM-N vaccines. At 5 dpc, the mortality, morbidity and virus re-isolation rate of the birds vaccinated with the rHBM-S1-N vaccine were slightly higher than those vaccinated with the H120 control vaccine but were lower than those vaccinated with the rHBM-S1 and rHBM-N vaccines. The present study demonstrated that the protection of the recombinant baculovirus co-expressing S1 and N proteins was better than that of recombinant baculoviruses mono-expressing the S1 or N protein. Thus, the recombinant baculovirus co-expressing S1 and N proteins could serve as a potential IBV vaccine and this demonstrates that the bivalent subunit vaccine including the S1 and N proteins might be a strategy for the development of an IBV subunit vaccine.",2018 Jun 27,"['Yuan, Yuan', 'Zhang, Zhi-Peng', 'He, Yi-Ning', 'Fan, Wen-Sheng', 'Dong, Zhi-Hua', 'Zhang, Li-Hua', 'Sun, Xin-Kuan', 'Song, Li-Li', 'Wei, Tian-Chao', 'Mo, Mei-Lan', 'Wei, Ping']",Viruses,,,False
4d9b9c94e5b2cd4016b42cdc8fbcb85fa908bc64,PMC,The Convergence of High-Consequence Livestock and Human Pathogen Research and Development: A Paradox of Zoonotic Disease,http://dx.doi.org/10.3390/tropicalmed3020055,PMC6073383,30274451,CC BY,"The World Health Organization (WHO) estimates that zoonotic diseases transmitted from animals to humans account for 75 percent of new and emerging infectious diseases. Globally, high-consequence pathogens that impact livestock and have the potential for human transmission create research paradoxes and operational challenges for the high-containment laboratories that conduct work with them. These specialized facilities are required for conducting all phases of research on high-consequence pathogens (basic, applied, and translational) with an emphasis on both the generation of fundamental knowledge and product development. To achieve this research mission, a highly-trained workforce is required and flexible operational methods are needed. In addition, working with certain pathogens requires compliance with regulations such as the Centers for Disease Control (CDC) and the U.S. Department of Agriculture (USDA) Select Agent regulations, which adds to the operational burden. The vast experience from the existing studies at Plum Island Animal Disease Center, other U.S. laboratories, and those in Europe and Australia with biosafety level 4 (BSL-4) facilities designed for large animals, clearly demonstrates the valuable contribution this capability brings to the efforts to detect, prepare, prevent and respond to livestock and potential zoonotic threats. To raise awareness of these challenges, which include biosafety and biosecurity issues, we held a workshop at the 2018 American Society for Microbiology (ASM) Biothreats conference to further discuss the topic with invited experts and audience participants. The workshop covered the subjects of research funding and metrics, economic sustainment of drug and vaccine development pipelines, workforce turnover, and the challenges of maintaining operational readiness of high containment laboratories.",2018 May 30,"['Michelotti, Julia M.', 'Yeh, Kenneth B.', 'Beckham, Tammy R.', 'Colby, Michelle M.', 'Dasgupta, Debanjana', 'Zuelke, Kurt A.', 'Olinger, Gene G.']",Trop Med Infect Dis,,,True
8b585680add23a7959772b785c2cb2afd82db152,PMC,Application of Gold Nanoparticle to Plasmonic Biosensors,http://dx.doi.org/10.3390/ijms19072021,PMC6073481,29997363,CC BY,"Gold nanoparticles (GNPs) have been widely utilized to develop various biosensors for molecular diagnosis, as they can be easily functionalized and exhibit unique optical properties explained by plasmonic effects. These unique optical properties of GNPs allow the expression of an intense color under light that can be tuned by altering their size, shape, composition, and coupling with other plasmonic nanoparticles. Additionally, they can also enhance other optical signals, such as fluorescence and Raman scattering, making them suitable for biosensor development. In this review, we provide a detailed discussion of the currently developed biosensors based on the aforementioned unique optical features of GNPs. Mainly, we focus on four different plasmonic biosensing methods, including localized surface plasmon resonance (LSPR), surface-enhanced Raman spectroscopy (SERS), fluorescence enhancement, and quenching caused by plasmon and colorimetry changes based on the coupling of GNPs. We believe that the topics discussed here are useful and able to provide a guideline in the development of novel GNP-based biosensors in the future.",2018 Jul 11,"['Lee, Jin-Ho', 'Cho, Hyeon-Yeol', 'Choi, Hye Kyu', 'Lee, Ji-Young', 'Choi, Jeong-Woo']",Int J Mol Sci,,,True
65e06f3980bdecbbbfc2f5018f79ec9ae44f3d04,PMC,A Review of Laboratory-Acquired Infections in the Asia-Pacific: Understanding Risk and the Need for Improved Biosafety for Veterinary and Zoonotic Diseases,http://dx.doi.org/10.3390/tropicalmed3020036,PMC6073996,30274433,CC BY,"A rapid review was performed to determine (1) the number and causes of reported laboratory-acquired infections (LAI) in the Asia-Pacific region; (2) their significance and threat to the community; (3) the primary risk factors associated with LAIs; (4) the consequences in the event of a LAI or pathogen escape; and (5) to make general recommendations regarding biosafety practices for diagnosis and research in the Asia-Pacific region. A search for LAI and zoonoses in the Asia-Pacific region using online search engines revealed a relatively low number of reports. Only 27 LAI reports were published between 1982 and 2016. The most common pathogens associated with LAIs were dengue virus, Arthroderma spp., Brucella spp., Mycobacterium spp., Rickettsia spp., and Shigella spp. Seventy-eight percent (21 out of 27 LAI reports) occurred in high-income countries (i.e., Australia, Japan, South Korea, Singapore, and Taiwan) where laboratories were likely to comply with international biosafety standards. Two upper-middle income countries (China (2), and Malaysia (2)) and one lower-middle income country (India (2)) reported LAI incidents. The majority of the reports (fifty-two percent (14/27)) of LAIs occurred in research laboratories. Five LAI reports were from clinical or diagnostic laboratories that are considered at the frontier for zoonotic disease detection. Governments and laboratories in the Asia-Pacific region should be encouraged to report LAI cases as it provides a useful tool to monitor unintended release of zoonotic pathogens and to further improve laboratory biosafety. Non-reporting of LAI events could pose a risk of disease transmission from infected laboratory staff to communities and the environment. The international community has an important and continuing role to play in supporting laboratories in the Asia-Pacific region to ensure that they maintain the safe working environment for the staff and their families, and the wider community.",2018 Mar 26,"['Siengsanan-Lamont, Jarunee', 'Blacksell, Stuart D.']",Trop Med Infect Dis,,,True
02f791c3ff683241cf1275092ccd53f1596f70d3,PMC,A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein,http://dx.doi.org/10.1038/s41467-018-05276-4,PMC6076265,30076287,CC BY,"Current efforts to develop Zika virus (ZIKV) subunit vaccines have been focused on pre-membrane (prM) and envelope (E) proteins, but the role of NS1 in ZIKV-specific immune response and protection is poorly understood. Here, we develop an attenuated recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing ZIKV prM-E-NS1 as a polyprotein. This vectored vaccine candidate is attenuated in mice, where a single immunization induces ZIKV-specific antibody and T cell immune responses that provide protection against ZIKV challenge. Co-expression of prM, E, and NS1 induces significantly higher levels of Th2 and Th17 cytokine responses than prM-E. In addition, NS1 alone is capable of conferring partial protection against ZIKV infection in mice even though it does not induce neutralizing antibodies. These results demonstrate that attenuated rVSV co-expressing prM, E, and NS1 is a promising vaccine candidate for protection against ZIKV infection and highlights an important role for NS1 in ZIKV-specific cellular immune responses.",2018 Aug 3,"['Li, Anzhong', 'Yu, Jingyou', 'Lu, Mijia', 'Ma, Yuanmei', 'Attia, Zayed', 'Shan, Chao', 'Xue, Miaoge', 'Liang, Xueya', 'Craig, Kelsey', 'Makadiya, Nirajkumar', 'He, Jennifer J.', 'Jennings, Ryan', 'Shi, Pei-Yong', 'Peeples, Mark E.', 'Liu, Shan-Lu', 'Boyaka, Prosper N.', 'Li, Jianrong']",Nat Commun,,,False
81bf72bed294b556985ff244cc7d00d7b0b2235e,PMC,A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein,http://dx.doi.org/10.1038/s41467-018-05276-4,PMC6076265,30076287,CC BY,"Current efforts to develop Zika virus (ZIKV) subunit vaccines have been focused on pre-membrane (prM) and envelope (E) proteins, but the role of NS1 in ZIKV-specific immune response and protection is poorly understood. Here, we develop an attenuated recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing ZIKV prM-E-NS1 as a polyprotein. This vectored vaccine candidate is attenuated in mice, where a single immunization induces ZIKV-specific antibody and T cell immune responses that provide protection against ZIKV challenge. Co-expression of prM, E, and NS1 induces significantly higher levels of Th2 and Th17 cytokine responses than prM-E. In addition, NS1 alone is capable of conferring partial protection against ZIKV infection in mice even though it does not induce neutralizing antibodies. These results demonstrate that attenuated rVSV co-expressing prM, E, and NS1 is a promising vaccine candidate for protection against ZIKV infection and highlights an important role for NS1 in ZIKV-specific cellular immune responses.",2018 Aug 3,"['Li, Anzhong', 'Yu, Jingyou', 'Lu, Mijia', 'Ma, Yuanmei', 'Attia, Zayed', 'Shan, Chao', 'Xue, Miaoge', 'Liang, Xueya', 'Craig, Kelsey', 'Makadiya, Nirajkumar', 'He, Jennifer J.', 'Jennings, Ryan', 'Shi, Pei-Yong', 'Peeples, Mark E.', 'Liu, Shan-Lu', 'Boyaka, Prosper N.', 'Li, Jianrong']",Nat Commun,,,True
f2d95ab758e878195eefa64325961667efeb4c14,PMC,A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein,http://dx.doi.org/10.1038/s41467-018-05276-4,PMC6076265,30076287,CC BY,"Current efforts to develop Zika virus (ZIKV) subunit vaccines have been focused on pre-membrane (prM) and envelope (E) proteins, but the role of NS1 in ZIKV-specific immune response and protection is poorly understood. Here, we develop an attenuated recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing ZIKV prM-E-NS1 as a polyprotein. This vectored vaccine candidate is attenuated in mice, where a single immunization induces ZIKV-specific antibody and T cell immune responses that provide protection against ZIKV challenge. Co-expression of prM, E, and NS1 induces significantly higher levels of Th2 and Th17 cytokine responses than prM-E. In addition, NS1 alone is capable of conferring partial protection against ZIKV infection in mice even though it does not induce neutralizing antibodies. These results demonstrate that attenuated rVSV co-expressing prM, E, and NS1 is a promising vaccine candidate for protection against ZIKV infection and highlights an important role for NS1 in ZIKV-specific cellular immune responses.",2018 Aug 3,"['Li, Anzhong', 'Yu, Jingyou', 'Lu, Mijia', 'Ma, Yuanmei', 'Attia, Zayed', 'Shan, Chao', 'Xue, Miaoge', 'Liang, Xueya', 'Craig, Kelsey', 'Makadiya, Nirajkumar', 'He, Jennifer J.', 'Jennings, Ryan', 'Shi, Pei-Yong', 'Peeples, Mark E.', 'Liu, Shan-Lu', 'Boyaka, Prosper N.', 'Li, Jianrong']",Nat Commun,,,True
44c4f131824378c773a3b2e006bed411214feec7,PMC,A Long-Term Study of a Lipid-Buprenorphine Implant in Rats,http://dx.doi.org/10.1155/2018/2616152,PMC6077592,30112418,CC BY,"Animal models to study opiates are of growing interest. We have examined the short-term safety of buprenorphine implants in Fischer F344/NTac rats treated with excess doses of a cholesterol-triglyceride suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of analgesia for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Here we report the results of a long-term follow-up study of female rats injected with 0.65 and 1.3 mg/kg. The 14-month evaluation showed no abnormal findings that could be attributed to the drug or lipid suspension. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery in laboratory animals and suggest that this model may be used to study long-term effects of opiate therapy.",2018 Jul 9,"['Guarnieri, Michael', 'Brayton, Cory', 'Tyler, Betty M.']",J Vet Med,,,True
af989f3b3f8bf8e0b3d8da323e3443a3f50ca2ce,PMC,Exogenous lipoid pneumonia: an important cause of interstitial lung disease in infants,http://dx.doi.org/10.1002/rcr2.356,PMC6079933,30094029,CC BY,"Exogenous lipoid pneumonia (ELP), an important cause of interstitial lung disease, often goes unrecognized. We conducted a retrospective study of children with histologically confirmed ELP at Red Cross Children’s Hospital, South Africa. Twelve children of Zimbabwean heritage aged 2.1–10.8 months were identified between 2012 and 2017. Repeated oral administration of plant‐based oil for cultural reasons was reported by 10 of 11 caregivers. Cough (12/12), tachypnoea (11/12), hypoxia (9/12), and diffuse alveolar infiltrates on chest radiography (12/12) were common at presentation. Chest computed tomography revealed ground‐glass opacification with lower zone predominance (9/9) and interlobular septal thickening (8/9). Bronchoalveolar lavage specimens appeared cloudy/milky, with abundant lipid‐laden macrophages and extracellular lipid on Oil‐Red‐O staining (12/12), with polymicrobial (6/12) and Mycobacterium abscessus (2/12) co‐infection. Antibiotics, systemic corticosteroids, and therapeutic lavage were interventions in all eight and five patients, respectively. Clinicians should consider ELP in children with non‐resolving pneumonia in settings with similar practices.",2018 Aug 7,"['Marangu, Diana', 'Pillay, Komala', 'Banderker, Ebrahim', 'Gray, Diane', 'Vanker, Aneesa', 'Zampoli, Marco']",Respirol Case Rep,,,True
cd501145689fd4bbd377e57583363920e99b1b6f,PMC,The increase in total knee replacement surgery in Taiwan: A 15-year retrospective study,http://dx.doi.org/10.1097/MD.0000000000011749,PMC6081077,30075592,CC BY,"Total knee replacement (TKR) is considered as one of the most success among clinical interventions for patients with who suffering from knee osteoarthritis (OA). We sought to estimate the incidence of TKR using demographics, incidence rates, lengths of hospital stay, and costs from 1996 to 2010 by analyzing Taiwan's National Health Insurance Research Database. A total of 154,553 patients obtained primary TKR surgery between 1996 and 2010. The diagnosis code for knee OA and the procedure code for TKR were selected from the records. To compare the rate of TKR between covariables, we calculated the TKR risk ratios and 95% confidence interval (CI) of these variables (gender, age, age group, and primary diagnoses). A 2-tailed P-value of .05 was considered statistically significant. The statistical package SPSS version 20.0 (SPSS, Chicago, IL) was used to conduct all the statistical analyzes. We analyzed 154,553 TKRs performed by surgeons in Taiwan from 1996 to 2010. The overall crude incidence increased from 26.4 to 74.55 TKR per 100,000 inhabitants from 1996 to 2010. TKR incidence for the 70 to 79 years age group increased from 227 to 505 per 100,000 people from 1996 to 2010. The age-standardized rate ratios for TKR of women to men ranged from 2.5 to 3.0. The mean average length of stay in hospital was 15 days in 1996 and decreased to 8 days in 2010. During the study period, the adjusted mean cost per patient decreased from US$7485 to US$4827. Health expenditures for TKR were 5% of total National Health Insurance expenditure every year. Over the 15-year period, Taiwan's TKR incidence tripled, which is consistent with population ageing. Arthritis will be a major public health issue in the ageing population in the future.",2018 Aug 3,"['Lin, Fu-Huang', 'Chen, Hsiang-Cheng', 'Lin, Chin', 'Chiu, Yu-Lung', 'Lee, Herng-Sheng', 'Chang, Hung', 'Huang, Guo-Shu', 'Chang, Hsueh-Lu', 'Yeh, Shih-Jen', 'Su, Wen', 'Wang, Chih-Chien', 'Su, Sui-Lung']",Medicine (Baltimore),,,True
66a6a5cb7b41fb6edd030629be7c455c079f47bf,PMC,Characterization of peritoneal cells from cats with experimentally-induced feline infectious peritonitis (FIP) using RNA-seq,http://dx.doi.org/10.1186/s13567-018-0578-y,PMC6081860,30086792,CC BY,"Laboratory cats were infected with a serotype I cat-passaged field strain of FIP virus (FIPV) and peritoneal cells harvested 2–3 weeks later at onset of lymphopenia, fever and serositis. Comparison peritoneal cells were collected from four healthy laboratory cats by peritoneal lavage and macrophages predominated in both populations. Differential mRNA expression analysis identified 5621 genes as deregulated in peritoneal cells from FIPV infected versus normal cats; 956 genes showed > 2.0 Log(2) Fold Change (Log(2)FC) and 1589 genes showed < −2.0 Log(2)FC. Eighteen significantly upregulated pathways were identified by InnateDB enrichment analysis. These pathways involved apoptosis, cytokine–cytokine receptor interaction, pathogen recognition, Jak-STAT signaling, NK cell mediated cytotoxicity, several chronic infectious diseases, graft versus host disease, allograft rejection and certain autoimmune disorders. Infected peritoneal macrophages were activated M1 type based on pattern of RNA expression. Apoptosis was found to involve large virus-laden peritoneal macrophages more than less mature macrophages, suggesting that macrophage death played a role in virus dissemination. Gene transcripts for MHC I but not II receptors were upregulated, while mRNA for receptors commonly associated with virus attachment and identified in other coronaviruses were either not detected (APN, L-SIGN), not deregulated (DDP-4) or down-regulated (DC-SIGN). However, the mRNA for FcγRIIIA (CD16A/ADCC receptor) was significantly upregulated, supporting entry of virus as an immune complex. Analysis of KEGG associated gene transcripts indicated that Th1 polarization overshadowed Th2 polarization, but the addition of relevant B cell associated genes previously linked to FIP macrophages tended to alter this perception.",2018 Aug 7,"['Watanabe, Rie', 'Eckstrand, Christina', 'Liu, Hongwei', 'Pedersen, Niels C.']",Vet Res,,,True
5f1066c0868ef0e9c5325de77d1ebbf40d6208ba,PMC,Human adenovirus load in respiratory tract secretions are predictors for disease severity in children with human adenovirus pneumonia,http://dx.doi.org/10.1186/s12985-018-1037-0,PMC6081882,30086789,CC BY,"BACKGROUND: Pneumonia is a serious public health issue and is concerned around the world. This study is to investigate the association between viral load in children with human adenovirus (HAdV) pneumonia and disease severity. METHODS: A total of 1313 cases of children hospitalized in Hunan Provincial People’s Hospital due to community acquired pneumonia (CAP) from April 2011 to May 2014 were enrolled in this study. Samples of nasopharyngeal aspirate were collected for the cohort. WHO criteria for CAP grading was emerged for pneumonia severity classification. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect 12 kinds of respiratory viruses. HAdV types were identified by nested PCR. The relationship between HAdV load and severity of disease was there by analyzed. RESULTS: Finally, 174 cases (174/1313, 13.3%) were positive for HAdV, and HAdV type 7 (HAdV-7) was the main serotype (76/174, 43.7%). Among the 174 cases, 70 cases were with HAdV infection alone and 104 cases were accompanied by other viruses. The patients were divided into mild pneumonia group (n = 108 cases) and severe pneumonia group (n = 66 cases). HAdV load of children in severe pneumonia group was higher than that in mild pneumonia group. Similar result was obtained in the 70 cases with HAdV infection alone after subgrouping. Relevant factors analysis results showed that severe pneumonia children presented lower onset age, more prone to fever, longer fever time, and longer hospital stay compared with that of mild pneumonia children. Children with HAdV-7 infection developed more frequently severe pneumonia. Multivariate regression analysis showed that HAdV load, age, and fever time were risk factors for pneumonia severity. CONCLUSION: The severity of HAdV infection is significantly correlated with viral load and serotype.",2018 Aug 7,"['Xie, Leyun', 'Zhang, Bing', 'Zhou, Jieying', 'Huang, Han', 'Zeng, Saizhen', 'Liu, Qin', 'Xie, Zhiping', 'Gao, Hanchun', 'Duan, Zhaojun', 'Zhong, Lili']",Virol J,,,True
f291cfbcb64f14deb49a2dcc95079a17e838cf85,PMC,Surveillance of respiratory viruses in the outpatient setting in rural coastal Kenya: baseline epidemiological observations,http://dx.doi.org/10.12688/wellcomeopenres.14662.1,PMC6081997,30175247,CC BY,"Background: Endemic and seasonally recurring respiratory viruses are a major cause of disease and death globally. The burden is particularly severe in developing countries. Improved understanding of the source of infection, pathways of spread and persistence in communities would be of benefit in devising intervention strategies. Methods: We report epidemiological data obtained through surveillance of respiratory viruses at nine outpatient health facilities within the Kilifi Health and Demographic Surveillance System, Kilifi County, coastal Kenya, between January and December 2016. Nasopharyngeal swabs were collected from individuals of all ages presenting with acute respiratory infection (ARI) symptoms (up to 15 swabs per week per facility) and screened for 15 respiratory viruses using real-time PCR. Paediatric inpatient surveillance at Kilifi County Hospital for respiratory viruses provided comparative data. Results: Over the year, 5,647 participants were sampled, of which 3,029 (53.7%) were aged <5 years. At least one target respiratory virus was detected in 2,380 (42.2%) of the samples; the most common being rhinovirus 18.6% (1,050), influenza virus 6.9% (390), coronavirus 6.8% (387), parainfluenza virus 6.6% (371), respiratory syncytial virus (RSV) 3.9% (219) and adenovirus 2.7% (155). Virus detections were higher among <5-year-olds compared to older children and adults (50.3% vs 32.7%, respectively; χ (2)(1) =177.3, P=0.0001). Frequency of viruses did not differ significantly by facility (χ (2)(8) =13.38, P=0.072). However, prevalence was significantly higher among inpatients than outpatients in <5-year-olds for RSV (22.1% vs 6.0%; χ (2)(1) = 159.4, P=0.0001), and adenovirus (12.4% vs 4.4%, χ (2)(1) =56.6, P=0.0001). Conclusions: Respiratory virus infections are common amongst ARI outpatients in this coastal Kenya setting, particularly in young children. Rhinovirus predominance warrants further studies on the health and socio-economic implications. RSV and adenovirus were more commonly associated with severe disease. Further analysis will explore epidemiological transmission patterns with the addition of virus sequence data.",2018 Jul 25,"['Nyiro, Joyce Uchi', 'Munywoki, Patrick', 'Kamau, Everlyn', 'Agoti, Charles', 'Gichuki, Alex', 'Etyang, Timothy', 'Otieno, Grieven', 'Nokes, D. James']",Wellcome Open Res,,,True
5cc7d19d8c064e59978daa0699ca18d5b139b0db,PMC,Human β-defensin 2 plays a regulatory role in innate antiviral immunity and is capable of potentiating the induction of antigen-specific immunity,http://dx.doi.org/10.1186/s12985-018-1035-2,PMC6083524,30089512,CC BY,"BACKGROUND: Antimicrobial peptides (AMPs) are primarily known for their innate immune defense against invading microorganisms, including viruses. In addition, recent research has suggested their modulatory activity in immune induction. Given that most subunit vaccines require an adjuvant to achieve effective immune induction through the activation of innate immunity, AMPs are plausible candidate molecules for stimulating not only innate immune but also adaptive immune responses. RESULTS: In this study, we investigated the ability of human β-defensin (HBD) 2 to promote antiviral immunity in vitro and in vivo using a receptor-binding domain (RBD) of Middle East respiratory syndrome-coronavirus (MERS-CoV) spike protein (S RBD) as a model antigen (Ag). When HBD 2-conjugated S RBD was used to treat THP-1 human monocytic cells, the expression levels of antiviral (IFN-β, IFN-γ, MxA, PKR, and RNaseL) and primary immune-inducing (NOD2, TNF-α, IL-1β, and IL-6) molecules were enhanced compared to those expressed after treatment with S RBD only. The expression of chemokines capable of recruiting leukocytes, including monocytes/macrophages, natural killer cells, granulocytes, T cells, and dendritic cells, was also increased following HBD 2-conjugated S RBD treatment. More important, immunization of mice with HBD 2-conjugated S RBD enhanced the immunogenicity of the S RBD and elicited a higher S RBD-specific neutralizing antibody response than S RBD alone. CONCLUSIONS: We conclude that HBD 2 activates the primary antiviral innate immune response and may also mediate the induction of an effective adaptive immune response against a conjugated Ag.",2018 Aug 8,"['Kim, Ju', 'Yang, Ye Lin', 'Jang, Sun-Hee', 'Jang, Yong-Suk']",Virol J,,,True
b20a6cf878e90b22d10ce2ddbd4c566a9b86fba2,PMC,Reovirus σNS and μNS Proteins Remodel the Endoplasmic Reticulum to Build Replication Neo-Organelles,http://dx.doi.org/10.1128/mBio.01253-18,PMC6083906,30087167,CC BY,"Like most viruses that replicate in the cytoplasm, mammalian reoviruses assemble membranous neo-organelles called inclusions that serve as sites of viral genome replication and particle morphogenesis. Viral inclusion formation is essential for viral infection, but how these organelles form is not well understood. We investigated the biogenesis of reovirus inclusions. Correlative light and electron microscopy showed that endoplasmic reticulum (ER) membranes are in contact with nascent inclusions, which form by collections of membranous tubules and vesicles as revealed by electron tomography. ER markers and newly synthesized viral RNA are detected in inclusion internal membranes. Live-cell imaging showed that early in infection, the ER is transformed into thin cisternae that fragment into small tubules and vesicles. We discovered that ER tubulation and vesiculation are mediated by the reovirus σNS and μNS proteins, respectively. Our results enhance an understanding of how viruses remodel cellular compartments to build functional replication organelles.",2018 Aug 7,"['Tenorio, Raquel', 'Fernández de Castro, Isabel', 'Knowlton, Jonathan J.', 'Zamora, Paula F.', 'Lee, Christopher H.', 'Mainou, Bernardo A.', 'Dermody, Terence S.', 'Risco, Cristina']",mBio,,,True
82f9ca4515f8b3eba2bb41f838f13e4a43f0e071,PMC,Reovirus σNS and μNS Proteins Remodel the Endoplasmic Reticulum to Build Replication Neo-Organelles,http://dx.doi.org/10.1128/mBio.01253-18,PMC6083906,30087167,CC BY,"Like most viruses that replicate in the cytoplasm, mammalian reoviruses assemble membranous neo-organelles called inclusions that serve as sites of viral genome replication and particle morphogenesis. Viral inclusion formation is essential for viral infection, but how these organelles form is not well understood. We investigated the biogenesis of reovirus inclusions. Correlative light and electron microscopy showed that endoplasmic reticulum (ER) membranes are in contact with nascent inclusions, which form by collections of membranous tubules and vesicles as revealed by electron tomography. ER markers and newly synthesized viral RNA are detected in inclusion internal membranes. Live-cell imaging showed that early in infection, the ER is transformed into thin cisternae that fragment into small tubules and vesicles. We discovered that ER tubulation and vesiculation are mediated by the reovirus σNS and μNS proteins, respectively. Our results enhance an understanding of how viruses remodel cellular compartments to build functional replication organelles.",2018 Aug 7,"['Tenorio, Raquel', 'Fernández de Castro, Isabel', 'Knowlton, Jonathan J.', 'Zamora, Paula F.', 'Lee, Christopher H.', 'Mainou, Bernardo A.', 'Dermody, Terence S.', 'Risco, Cristina']",mBio,,,False
3adb306678a2a91d42d0ae445fbcdb0e88e4df99,PMC,Reovirus σNS and μNS Proteins Remodel the Endoplasmic Reticulum to Build Replication Neo-Organelles,http://dx.doi.org/10.1128/mBio.01253-18,PMC6083906,30087167,CC BY,"Like most viruses that replicate in the cytoplasm, mammalian reoviruses assemble membranous neo-organelles called inclusions that serve as sites of viral genome replication and particle morphogenesis. Viral inclusion formation is essential for viral infection, but how these organelles form is not well understood. We investigated the biogenesis of reovirus inclusions. Correlative light and electron microscopy showed that endoplasmic reticulum (ER) membranes are in contact with nascent inclusions, which form by collections of membranous tubules and vesicles as revealed by electron tomography. ER markers and newly synthesized viral RNA are detected in inclusion internal membranes. Live-cell imaging showed that early in infection, the ER is transformed into thin cisternae that fragment into small tubules and vesicles. We discovered that ER tubulation and vesiculation are mediated by the reovirus σNS and μNS proteins, respectively. Our results enhance an understanding of how viruses remodel cellular compartments to build functional replication organelles.",2018 Aug 7,"['Tenorio, Raquel', 'Fernández de Castro, Isabel', 'Knowlton, Jonathan J.', 'Zamora, Paula F.', 'Lee, Christopher H.', 'Mainou, Bernardo A.', 'Dermody, Terence S.', 'Risco, Cristina']",mBio,,,False
65ce97d5c30730b91e9408fd7e954cb39add0b2d,PMC,Reovirus σNS and μNS Proteins Remodel the Endoplasmic Reticulum to Build Replication Neo-Organelles,http://dx.doi.org/10.1128/mBio.01253-18,PMC6083906,30087167,CC BY,"Like most viruses that replicate in the cytoplasm, mammalian reoviruses assemble membranous neo-organelles called inclusions that serve as sites of viral genome replication and particle morphogenesis. Viral inclusion formation is essential for viral infection, but how these organelles form is not well understood. We investigated the biogenesis of reovirus inclusions. Correlative light and electron microscopy showed that endoplasmic reticulum (ER) membranes are in contact with nascent inclusions, which form by collections of membranous tubules and vesicles as revealed by electron tomography. ER markers and newly synthesized viral RNA are detected in inclusion internal membranes. Live-cell imaging showed that early in infection, the ER is transformed into thin cisternae that fragment into small tubules and vesicles. We discovered that ER tubulation and vesiculation are mediated by the reovirus σNS and μNS proteins, respectively. Our results enhance an understanding of how viruses remodel cellular compartments to build functional replication organelles.",2018 Aug 7,"['Tenorio, Raquel', 'Fernández de Castro, Isabel', 'Knowlton, Jonathan J.', 'Zamora, Paula F.', 'Lee, Christopher H.', 'Mainou, Bernardo A.', 'Dermody, Terence S.', 'Risco, Cristina']",mBio,,,False
ef6e986449af3133f8f37e8631bb51c9d02b1e1a,PMC,Reovirus σNS and μNS Proteins Remodel the Endoplasmic Reticulum to Build Replication Neo-Organelles,http://dx.doi.org/10.1128/mBio.01253-18,PMC6083906,30087167,CC BY,"Like most viruses that replicate in the cytoplasm, mammalian reoviruses assemble membranous neo-organelles called inclusions that serve as sites of viral genome replication and particle morphogenesis. Viral inclusion formation is essential for viral infection, but how these organelles form is not well understood. We investigated the biogenesis of reovirus inclusions. Correlative light and electron microscopy showed that endoplasmic reticulum (ER) membranes are in contact with nascent inclusions, which form by collections of membranous tubules and vesicles as revealed by electron tomography. ER markers and newly synthesized viral RNA are detected in inclusion internal membranes. Live-cell imaging showed that early in infection, the ER is transformed into thin cisternae that fragment into small tubules and vesicles. We discovered that ER tubulation and vesiculation are mediated by the reovirus σNS and μNS proteins, respectively. Our results enhance an understanding of how viruses remodel cellular compartments to build functional replication organelles.",2018 Aug 7,"['Tenorio, Raquel', 'Fernández de Castro, Isabel', 'Knowlton, Jonathan J.', 'Zamora, Paula F.', 'Lee, Christopher H.', 'Mainou, Bernardo A.', 'Dermody, Terence S.', 'Risco, Cristina']",mBio,,,False
deb4eead8e0eb2a9530fd8c711a7e4e2577169be,PMC,Reovirus σNS and μNS Proteins Remodel the Endoplasmic Reticulum to Build Replication Neo-Organelles,http://dx.doi.org/10.1128/mBio.01253-18,PMC6083906,30087167,CC BY,"Like most viruses that replicate in the cytoplasm, mammalian reoviruses assemble membranous neo-organelles called inclusions that serve as sites of viral genome replication and particle morphogenesis. Viral inclusion formation is essential for viral infection, but how these organelles form is not well understood. We investigated the biogenesis of reovirus inclusions. Correlative light and electron microscopy showed that endoplasmic reticulum (ER) membranes are in contact with nascent inclusions, which form by collections of membranous tubules and vesicles as revealed by electron tomography. ER markers and newly synthesized viral RNA are detected in inclusion internal membranes. Live-cell imaging showed that early in infection, the ER is transformed into thin cisternae that fragment into small tubules and vesicles. We discovered that ER tubulation and vesiculation are mediated by the reovirus σNS and μNS proteins, respectively. Our results enhance an understanding of how viruses remodel cellular compartments to build functional replication organelles.",2018 Aug 7,"['Tenorio, Raquel', 'Fernández de Castro, Isabel', 'Knowlton, Jonathan J.', 'Zamora, Paula F.', 'Lee, Christopher H.', 'Mainou, Bernardo A.', 'Dermody, Terence S.', 'Risco, Cristina']",mBio,,,False
d5066cf95471ee885eb17e94e431fc5658cf1b1a,PMC,Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses,http://dx.doi.org/10.1128/mBio.01408-18,PMC6083907,30087171,CC BY,"Against a backdrop of seasonal influenza virus epidemics, emerging avian influenza viruses (AIVs) occasionally jump from birds to humans, posing a public health risk, especially with the recent sharp increase in H7N9 infections. Evaluations of cross-reactive T-cell immunity to seasonal influenza viruses and human-infecting AIVs have been reported previously. However, the roles of influenza A virus-derived epitopes in the cross-reactive T-cell responses and heterosubtypic protections are not well understood; understanding those roles is important for preventing and controlling new emerging AIVs. Here, among the members of a healthy population presumed to have previously been infected by pandemic H1N1 (pH1N1), we found that pH1N1-specific T cells showed cross- but biased reactivity to human-infecting AIVs, i.e., H5N1, H6N1, H7N9, and H9N2, which correlates with distinct protections. Through a T-cell epitope-based phylogenetic analysis, the cellular immunogenic clustering expanded the relevant conclusions to a broader range of virus strains. We defined the potential key conserved epitopes required for cross-protection and revealed the molecular basis for the immunogenic variations. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development.",2018 Aug 7,"['Zhao, Min', 'Liu, Kefang', 'Luo, Jiejian', 'Tan, Shuguang', 'Quan, Chuansong', 'Zhang, Shuijun', 'Chai, Yan', 'Qi, Jianxun', 'Li, Yan', 'Bi, Yuhai', 'Xiao, Haixia', 'Wong, Gary', 'Zhou, Jianfang', 'Jiang, Taijiao', 'Liu, Wenjun', 'Yu, Hongjie', 'Yan, Jinghua', 'Liu, Yingxia', 'Shu, Yuelong', 'Wu, Guizhen', 'Wu, Aiping', 'Gao, George F.', 'Liu, William J.']",mBio,,,True
984c854e60de843d117387c36431579501b6f0d3,PMC,Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses,http://dx.doi.org/10.1128/mBio.01408-18,PMC6083907,30087171,CC BY,"Against a backdrop of seasonal influenza virus epidemics, emerging avian influenza viruses (AIVs) occasionally jump from birds to humans, posing a public health risk, especially with the recent sharp increase in H7N9 infections. Evaluations of cross-reactive T-cell immunity to seasonal influenza viruses and human-infecting AIVs have been reported previously. However, the roles of influenza A virus-derived epitopes in the cross-reactive T-cell responses and heterosubtypic protections are not well understood; understanding those roles is important for preventing and controlling new emerging AIVs. Here, among the members of a healthy population presumed to have previously been infected by pandemic H1N1 (pH1N1), we found that pH1N1-specific T cells showed cross- but biased reactivity to human-infecting AIVs, i.e., H5N1, H6N1, H7N9, and H9N2, which correlates with distinct protections. Through a T-cell epitope-based phylogenetic analysis, the cellular immunogenic clustering expanded the relevant conclusions to a broader range of virus strains. We defined the potential key conserved epitopes required for cross-protection and revealed the molecular basis for the immunogenic variations. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development.",2018 Aug 7,"['Zhao, Min', 'Liu, Kefang', 'Luo, Jiejian', 'Tan, Shuguang', 'Quan, Chuansong', 'Zhang, Shuijun', 'Chai, Yan', 'Qi, Jianxun', 'Li, Yan', 'Bi, Yuhai', 'Xiao, Haixia', 'Wong, Gary', 'Zhou, Jianfang', 'Jiang, Taijiao', 'Liu, Wenjun', 'Yu, Hongjie', 'Yan, Jinghua', 'Liu, Yingxia', 'Shu, Yuelong', 'Wu, Guizhen', 'Wu, Aiping', 'Gao, George F.', 'Liu, William J.']",mBio,,,False
da94b19f0c776024cff8f484a52c26793ed65a74,PMC,Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses,http://dx.doi.org/10.1128/mBio.01408-18,PMC6083907,30087171,CC BY,"Against a backdrop of seasonal influenza virus epidemics, emerging avian influenza viruses (AIVs) occasionally jump from birds to humans, posing a public health risk, especially with the recent sharp increase in H7N9 infections. Evaluations of cross-reactive T-cell immunity to seasonal influenza viruses and human-infecting AIVs have been reported previously. However, the roles of influenza A virus-derived epitopes in the cross-reactive T-cell responses and heterosubtypic protections are not well understood; understanding those roles is important for preventing and controlling new emerging AIVs. Here, among the members of a healthy population presumed to have previously been infected by pandemic H1N1 (pH1N1), we found that pH1N1-specific T cells showed cross- but biased reactivity to human-infecting AIVs, i.e., H5N1, H6N1, H7N9, and H9N2, which correlates with distinct protections. Through a T-cell epitope-based phylogenetic analysis, the cellular immunogenic clustering expanded the relevant conclusions to a broader range of virus strains. We defined the potential key conserved epitopes required for cross-protection and revealed the molecular basis for the immunogenic variations. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development.",2018 Aug 7,"['Zhao, Min', 'Liu, Kefang', 'Luo, Jiejian', 'Tan, Shuguang', 'Quan, Chuansong', 'Zhang, Shuijun', 'Chai, Yan', 'Qi, Jianxun', 'Li, Yan', 'Bi, Yuhai', 'Xiao, Haixia', 'Wong, Gary', 'Zhou, Jianfang', 'Jiang, Taijiao', 'Liu, Wenjun', 'Yu, Hongjie', 'Yan, Jinghua', 'Liu, Yingxia', 'Shu, Yuelong', 'Wu, Guizhen', 'Wu, Aiping', 'Gao, George F.', 'Liu, William J.']",mBio,,,False
73e5c3bd09c484f93ebc67569055ef39cbd6080d,PMC,Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses,http://dx.doi.org/10.1128/mBio.01408-18,PMC6083907,30087171,CC BY,"Against a backdrop of seasonal influenza virus epidemics, emerging avian influenza viruses (AIVs) occasionally jump from birds to humans, posing a public health risk, especially with the recent sharp increase in H7N9 infections. Evaluations of cross-reactive T-cell immunity to seasonal influenza viruses and human-infecting AIVs have been reported previously. However, the roles of influenza A virus-derived epitopes in the cross-reactive T-cell responses and heterosubtypic protections are not well understood; understanding those roles is important for preventing and controlling new emerging AIVs. Here, among the members of a healthy population presumed to have previously been infected by pandemic H1N1 (pH1N1), we found that pH1N1-specific T cells showed cross- but biased reactivity to human-infecting AIVs, i.e., H5N1, H6N1, H7N9, and H9N2, which correlates with distinct protections. Through a T-cell epitope-based phylogenetic analysis, the cellular immunogenic clustering expanded the relevant conclusions to a broader range of virus strains. We defined the potential key conserved epitopes required for cross-protection and revealed the molecular basis for the immunogenic variations. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development.",2018 Aug 7,"['Zhao, Min', 'Liu, Kefang', 'Luo, Jiejian', 'Tan, Shuguang', 'Quan, Chuansong', 'Zhang, Shuijun', 'Chai, Yan', 'Qi, Jianxun', 'Li, Yan', 'Bi, Yuhai', 'Xiao, Haixia', 'Wong, Gary', 'Zhou, Jianfang', 'Jiang, Taijiao', 'Liu, Wenjun', 'Yu, Hongjie', 'Yan, Jinghua', 'Liu, Yingxia', 'Shu, Yuelong', 'Wu, Guizhen', 'Wu, Aiping', 'Gao, George F.', 'Liu, William J.']",mBio,,,False
67b6aa7293bbb9a8fed752ae0e96553f4f5c44aa,PMC,Label‐Free Quantitative Proteomic Analysis of Differentially Expressed Membrane Proteins of Pulmonary Alveolar Macrophages Infected with Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Its Attenuated Strain,http://dx.doi.org/10.1002/pmic.201700101,PMC6084361,29052333,CC BY,"Significant differences exist between the highly pathogenic (HP) porcine reproductive and respiratory syndrome virus (PRRSV) and its attenuated pathogenic (AP) strain in the ability to infect host cells. The mechanisms by which different virulent strains invade host cells remain relatively unknown. In this study, pulmonary alveolar macrophages (PAMs) are infected with HP‐PRRSV (HuN4) and AP‐PRRSV (HuN4‐F112) for 24 h, then harvested and subjected to label‐free quantitative MS. A total of 2849 proteins are identified, including 95 that are differentially expressed. Among them, 26 proteins are located on the membrane. The most differentially expressed proteins are involved in response to stimulus, metabolic process, and immune system process, which mainly have the function of binding and catalytic activity. Cluster of differentiation CD163, vimentin (VIM), and nmII as well as detected proteins are assessed together by string analysis, which elucidated a potentially different infection mechanism. According to the function annotations, PRRSV with different virulence may mainly differ in immunology, inflammation, immune evasion as well as cell apoptosis. This is the first attempt to explore the differential characteristics between HP‐PRRSV and its attenuated PRRSV infected PAMs focusing on membrane proteins which will be of great help to further understand the different infective mechanisms of HP‐PRRSV and AP‐PRRSV.",2017 Dec 24,"['Qu, Zehui', 'Gao, Fei', 'Li, Liwei', 'Zhang, Yujiao', 'Jiang, Yifeng', 'Yu, Lingxue', 'Zhou, Yanjun', 'Zheng, Hao', 'Tong, Wu', 'Li, Guoxin', 'Tong, Guangzhi']",Proteomics,,,True
7478489aca4d8ade51ecf485914211cd3313d3b5,PMC,Correlation of microbiological yield with radiographic activity on chest computed tomography in cases of suspected pulmonary tuberculosis,http://dx.doi.org/10.1371/journal.pone.0201748,PMC6084932,30091997,CC BY,"BACKGROUND: Little is known about the correlation between microbiological yield and radiographic activity, on chest computed tomography (CT), in suspected pulmonary tuberculosis (PTB) cases, despite CT being widely used, clinically. METHODS: We used multicenter retrospective data, obtained from medical records, focusing on the diagnostic performance for definite PTB. We categorized patients into four groups, by radiographic activity: definitely active, probably active, indeterminate activity, and probably inactive. RESULTS: Of the 650 patients included, 316 had culture-confirmed PTB; 190 (29.2%), 323 (49.7%), 70 (10.8%), and 67 (10.3%) were classified into the definitely active, probably active, indeterminate activity, and probably inactive groups, respectively. The corresponding observed culture rates for CT radiographic activity were 61.6%, 60.7%, 4.3% and 0%, respectively. When not only culture rates but TB-PCR and histological results were taken into consideration as definite PTB, it showed 66.6%, 67.2%, 14.3%, and 0% of each CT radiographic activity, respectively. Regarding the diagnostic performance for definite PTB, radiographic activity displayed high sensitivity (97.1%, 95% confidence interval (CI), 94.6–98.5) and negative predictive values (92.7%, 95% CI, 86.6–96.2), considered definitely and probably active PTB. Apart from PTB, other etiologies, according to radiographic activity, were predominantly respiratory infections such as bacterial pneumonia and non-tuberculous mycobacterial infection. CONCLUSIONS: Radiographic activity showed good diagnostic performance, and can be used easily in clinical practice. However, clinicians should consider other possibilities, because radiologic images do not confirm microbiological PTB.",2018 Aug 9,"['Ko, Yousang', 'Lee, Ho Young', 'Park, Yong Bum', 'Hong, Su Jin', 'Shin, Jeong Hwan', 'Choi, Seok Jin', 'Kim, Changhwan', 'Park, So Young', 'Jeong, Jin Young']",PLoS One,,,True
e5982e467e81a52787bc1c653fc65fa444501032,PMC,Bat pathogens hit the road: But which one?,http://dx.doi.org/10.1371/journal.ppat.1007134,PMC6085074,30092093,CC BY,,2018 Aug 9,"['Joffrin, Léa', 'Dietrich, Muriel', 'Mavingui, Patrick', 'Lebarbenchon, Camille']",PLoS Pathog,,,True
1579fbff7af9b156c6f49fee0526e48f852ea460,PMC,A Recombinant Newcastle Disease Virus (NDV) Expressing S Protein of Infectious Bronchitis Virus (IBV) Protects Chickens against IBV and NDV,http://dx.doi.org/10.1038/s41598-018-30356-2,PMC6086832,30097608,CC BY,"Infectious bronchitis virus (IBV) causes a highly contagious respiratory, reproductive and urogenital tract disease in chickens worldwide, resulting in substantial economic losses for the poultry industry. Currently, live-attenuated IBV vaccines are used to control the disease. However, safety, attenuation and immunization outcomes of current vaccines are not guaranteed. Several studies indicate that attenuated IBV vaccine strains contribute to the emergence of variant viruses in the field due to mutations and recombination. Therefore, there is a need to develop a stable and safe IBV vaccine that will not create variant viruses. In this study, we generated recombinant Newcastle disease viruses (rNDVs) expressing the S1, S2 and S proteins of IBV using reverse genetics technology. Our results showed that the rNDV expressing the S protein of IBV provided better protection than the rNDV expressing S1 or S2 protein of IBV, indicating that the S protein is the best protective antigen of IBV. Immunization of 4-week-old SPF chickens with the rNDV expressing S protein elicited IBV-specific neutralizing antibodies and provided complete protection against virulent IBV and virulent NDV challenges. These results suggest that the rNDV expressing the S protein of IBV is a safe and effective bivalent vaccine candidate for both IBV and NDV.",2018 Aug 10,"['Shirvani, Edris', 'Paldurai, Anandan', 'Manoharan, Vinoth K.', 'Varghese, Berin P.', 'Samal, Siba K.']",Sci Rep,,,True
38c1c195de7abd1d3319ab5dfedb585f6cbbda85,PMC,The WHO global influenza surveillance and response system (GISRS)—A future perspective,http://dx.doi.org/10.1111/irv.12565,PMC6086842,29722140,CC BY,"In the centenary year of the devastating 1918‐19 pandemic, it seems opportune to reflect on the success of the WHO Global Influenza Surveillance and Response System (GISRS) initiated 70 years ago to provide early warning of changes in influenza viruses circulating in the global population to help mitigate the consequences of such a pandemic and maintain the efficacy of seasonal influenza vaccines. Three pandemics later and in the face of pandemic threats from highly pathogenic zoonotic infections by different influenza A subtypes, it continues to represent a model platform for global collaboration and timely sharing of viruses, reagents and information to forestall and respond to public health emergencies.",2018 Sep 25,"['Hay, Alan J', 'McCauley, John W']",Influenza Other Respir Viruses,,,True
98c8f0c6a7721035d1b32934f84b8b7b18834c81,PMC,Expanding severe acute respiratory infection (SARI) surveillance beyond influenza: The process and data from 1 year of implementation in Vietnam,http://dx.doi.org/10.1111/irv.12571,PMC6086843,29754431,CC BY,"BACKGROUND: In 2016, as a component of the Global Health Security Agenda, the Vietnam Ministry of Health expanded its existing influenza sentinel surveillance for severe acute respiratory infections (SARI) to include testing for 7 additional viral respiratory pathogens. This article describes the steps taken to implement expanded SARI surveillance in Vietnam and reports data from 1 year of expanded surveillance. METHODS: The process of expanding the suite of pathogens for routine testing by real‐time reverse transcriptase–polymerase chain reaction (rRT‐PCR) included laboratory trainings, procurement/distribution of reagents, and strengthening and aligning SARI surveillance epidemiology practices at sentinel sites and regional institutes (RI). RESULTS: Surveillance data showed that of 4003 specimens tested by the RI laboratories, 20.2% (n = 810) were positive for influenza virus. Of the 3193 influenza‐negative specimens, 41.8% (n = 1337) were positive for at least 1 non‐influenza respiratory virus, of which 16.2% (n = 518), 13.4% (n = 428), and 9.6% (n = 308) tested positive for respiratory syncytial virus, rhinovirus, and adenovirus, respectively. CONCLUSIONS: The Government of Vietnam has demonstrated that expanding respiratory viral surveillance by strengthening and building upon an influenza platform is feasible, efficient, and practical.",2018 Sep 10,"['Alroy, Karen A.', 'Do, Trang Thuy', 'Tran, Phu Dac', 'Dang, Tan Quang', 'Vu, Long Ngoc', 'Le, Nga Thi Hang', 'Dang, Anh Duc', 'Ngu, Nghia Duy', 'Ngo, Tu Huy', 'Hoang, Phuong Vu Mai', 'Phan, Lan Trong', 'Nguyen, Thuong Vu', 'Nguyen, Long Thanh', 'Nguyen, Thinh Viet', 'Vien, Mai Quang', 'Le, Huy Xuan', 'Dao, Anh The', 'Nguyen, Trieu Bao', 'Pham, Duoc Tho', 'Nguyen, Van Thi Tuyet', 'Pham, Thanh Ngoc', 'Phan, Binh Hai', 'Whitaker, Brett', 'Do, Thuy Thi Thu', 'Dao, Phuong Anh', 'Balajee, S. Arunmozhi', 'Mounts, Anthony W.']",Influenza Other Respir Viruses,,,True
32ffbe671caf791831bb7516b550b4b27240a5f0,PMC,Factors associated with recovery delay in a sample of patients diagnosed by MERS‐CoV rRT‐PCR: A Saudi Arabian multicenter retrospective study,http://dx.doi.org/10.1111/irv.12560,PMC6086845,29624866,CC BY,"BACKGROUND: Research evidence exists that poor prognosis is common in Middle East respiratory syndrome coronavirus (MERS‐CoV) patients. OBJECTIVES: This study estimates recovery delay intervals and identifies associated factors in a sample of Saudi Arabian patients admitted for suspected MERS‐CoV and diagnosed by rRT‐PCR assay. METHODS: A multicenter retrospective study was conducted on 829 patients admitted between September 2012 and June 2016 and diagnosed by rRT‐PCR procedures to have MERS‐CoV and non‐MERS‐CoV infection in which 396 achieved recovery. Detailed medical charts were reviewed for each patient who achieved recovery. Time intervals in days were calculated from presentation to the initial rRT‐PCR diagnosis (diagnosis delay) and from the initial rRT‐PCR diagnosis to recovery (recovery delay). RESULTS: The median recovery delay in our sample was 5 days. According to the multivariate negative binomial model, elderly (age ≥ 65), MERS‐CoV infection, ICU admission, and abnormal radiology findings were associated with longer recovery delay (adjusted relative risk (aRR): 1.741, 2.138, 2.048, and 1.473, respectively). Camel contact and the presence of respiratory symptoms at presentation were associated with a shorter recovery delay (expedited recovery) (aRR: 0.267 and 0.537, respectively). Diagnosis delay is a positive predictor for recovery delay (r = .421; P = .001). CONCLUSIONS: The study evidence supports that longer recovery delay was seen in patients of older age, MERS‐CoV infection, ICU admission, and abnormal radiology findings. Shorter recovery delay was found in patients who had camel contact and respiratory symptoms at presentation. These findings may help us understand clinical decision making on directing hospital resources toward prompt screening, monitoring, and implementing clinical recovery and treatment strategies.",2018 Sep 25,"['Ahmed, Anwar E.', 'Al‐Jahdali, Hamdan', 'Alaqeel, Mody', 'Siddiq, Salma S.', 'Alsaab, Hanan A.', 'Sakr, Ezzeldin A.', 'Alyahya, Hamed A.', 'Alandonisi, Munzir M.', 'Subedar, Alaa T.', 'Ali, Yosra Z.', 'Al Otaibi, Hazza', 'Aloudah, Nouf M.', 'Baharoon, Salim', 'Al Johani, Sameera', 'Alghamdi, Mohammed G.']",Influenza Other Respir Viruses,,,True
cfeab2d69cb124669b131e9e97c35dcb29e6ab28,PMC,65 years of influenza surveillance by a World Health Organization‐coordinated global network,http://dx.doi.org/10.1111/irv.12570,PMC6086847,29727518,CC BY,"The 1918 devastating influenza pandemic left a lasting impact on influenza experts and the public, and the importance of global influenza surveillance was soon recognized. The World Health Organization (WHO) Global Influenza Surveillance Network (GISN) was founded in 1952 and renamed to Global Influenza Surveillance and Response System in 2011 upon the adoption by the World Health Assembly, of the Pandemic Influenza Preparedness Framework for the Sharing of Influenza Viruses and Access to Vaccines and Other Benefits (“PIP Framework”). The importance of influenza surveillance had been recognized and promoted by experts prior to the years leading up to the establishment of WHO. In the 65 years of its existence, the Network has grown to comprise 143 National Influenza Centers recognized by WHO, 6 WHO Collaborating Centers, 4 Essential Regulatory Laboratories, and 13 H5 Reference Laboratories. The Network has proven its excellence throughout these 65 years, providing detailed information on circulating seasonal influenza viruses, as well as immediate response to the influenza pandemics in 1957, 1968, and 2009, and to threats caused by animal influenza viruses and by zoonotic transmission of coronaviruses. For its central role in global public health, the Network has been highly recognized by its many partners and by international bodies. Several generations of world‐renowned influenza scientists have brought the Network to where it is now and they will take it forward to the future, as influenza will remain a preeminent threat to humans and to animals.",2018 Sep 25,"['Ziegler, Thedi', 'Mamahit, Awandha', 'Cox, Nancy J.']",Influenza Other Respir Viruses,,,True
99f70ba1e268514c14cbbebc998becbc92e2c386,PMC,Development of a short course on management of critically ill patients with acute respiratory infection and impact on clinician knowledge in resource‐limited intensive care units,http://dx.doi.org/10.1111/irv.12569,PMC6086848,29727522,CC BY,"BACKGROUND: The 2009 influenza A (H1N1) pandemic caused surges of patients in intensive care units (ICUs) in resource‐limited settings. Several Ministries of Health requested clinical management guidance from the World Health Organization (WHO), which had not previously developed guidance regarding critically ill patients. OBJECTIVE: To assess the acceptability and impact on knowledge of a short course about the management of critically ill patients with acute respiratory infections complicated by sepsis or acute respiratory distress syndrome delivered to clinicians in resource‐limited ICUs. METHODS: Over 4 years (2009‐2013), WHO led the development, piloting, implementation and preliminary evaluation of a 3‐day course that emphasized patient management based on evidence‐based guidelines and used interactive adult‐learner teaching methodology. International content experts (n = 35) and instructional designers contributed to development. We assessed participants’ satisfaction and content knowledge before and after the course. RESULTS: The course was piloted among clinicians in Trinidad and Tobago (n = 29), Indonesia (n = 38) and Vietnam (n = 86); feedback from these courses contributed to the final version. In 2013, inaugural national courses were delivered in Tajikistan (n = 28), Uzbekistan (n = 39) and Azerbaijan (n = 30). Participants rated the course highly and demonstrated increased immediate content knowledge after (vs before) course completion (P < .001). CONCLUSIONS: We found that it was feasible to create and deliver a focused critical care short course to clinicians in low‐ and middle‐income countries. Collaboration between WHO, clinical experts, instructional designers, Ministries of Health and local clinician‐leaders facilitated course delivery. Future work should assess its impact on longer‐term knowledge retention and on processes and outcomes of care.",2018 Sep 26,"['Diaz, Janet V.', 'Ortiz, Justin R.', 'Lister, Paula', 'Shindo, Nahoko', 'Adhikari, Neill K.J.', None]",Influenza Other Respir Viruses,,,True
ca04ce1ec6ebeed591eeaefdf378fa6aaaf91afc,PMC,Development of a short course on management of critically ill patients with acute respiratory infection and impact on clinician knowledge in resource‐limited intensive care units,http://dx.doi.org/10.1111/irv.12569,PMC6086848,29727522,CC BY,"BACKGROUND: The 2009 influenza A (H1N1) pandemic caused surges of patients in intensive care units (ICUs) in resource‐limited settings. Several Ministries of Health requested clinical management guidance from the World Health Organization (WHO), which had not previously developed guidance regarding critically ill patients. OBJECTIVE: To assess the acceptability and impact on knowledge of a short course about the management of critically ill patients with acute respiratory infections complicated by sepsis or acute respiratory distress syndrome delivered to clinicians in resource‐limited ICUs. METHODS: Over 4 years (2009‐2013), WHO led the development, piloting, implementation and preliminary evaluation of a 3‐day course that emphasized patient management based on evidence‐based guidelines and used interactive adult‐learner teaching methodology. International content experts (n = 35) and instructional designers contributed to development. We assessed participants’ satisfaction and content knowledge before and after the course. RESULTS: The course was piloted among clinicians in Trinidad and Tobago (n = 29), Indonesia (n = 38) and Vietnam (n = 86); feedback from these courses contributed to the final version. In 2013, inaugural national courses were delivered in Tajikistan (n = 28), Uzbekistan (n = 39) and Azerbaijan (n = 30). Participants rated the course highly and demonstrated increased immediate content knowledge after (vs before) course completion (P < .001). CONCLUSIONS: We found that it was feasible to create and deliver a focused critical care short course to clinicians in low‐ and middle‐income countries. Collaboration between WHO, clinical experts, instructional designers, Ministries of Health and local clinician‐leaders facilitated course delivery. Future work should assess its impact on longer‐term knowledge retention and on processes and outcomes of care.",2018 Sep 26,"['Diaz, Janet V.', 'Ortiz, Justin R.', 'Lister, Paula', 'Shindo, Nahoko', 'Adhikari, Neill K.J.', None]",Influenza Other Respir Viruses,,,True
e7ec7ae8528004b91b84a51d4752a0bd5b70d2f7,PMC,"Human coronaviruses and other respiratory infections in young adults on a university campus: Prevalence, symptoms, and shedding",http://dx.doi.org/10.1111/irv.12563,PMC6086849,29660826,CC BY,"BACKGROUND: The prevalence, symptom course, and shedding in persons infected with the 4 most common human coronaviruses (HCoV)‐229E, HKU1, NL63, and OC43 are poorly described. OBJECTIVES: We estimate their prevalence and associated symptoms among college students identified via a social network study design. PATIENTS/METHODS: We collected 1‐3 samples (n = 250 specimens) from 176 participants between October 2012 and January 17, 2013: participants with acute respiratory infection (ARI; cough and body aches or chills or fever/feverishness) and their social contacts. Virus was detected using RT‐PCR. RESULTS: 30.4% (76/250) of specimens tested positive for any virus tested, and 4.8% (12/250) were positive for 2 or more viruses. Human coronaviruses (HCoVs [22.0%; 55/250]), rhinovirus (7.6%; 19/250), and influenza A (6.4%; 16/250) were most prevalent. Symptoms changed significantly over time among ARI participants with HCoV: the prevalence of cough and chills decreased over 6 days (P = .04, and P = .01, respectively), while runny nose increased over the same period (P = .02). HCoV‐NL63 was the most frequent virus detected 6 days following symptom onset (8.9%), followed by rhinovirus (6.7%). CONCLUSIONS: During a 3‐month period covering a single season, HCoVs were common, even among social contacts without respiratory symptoms; specific symptoms may change over the course of HCoV‐associated illness and were similar to symptoms from influenza and rhinovirus.",2018 Sep 24,"['Davis, Brian M.', 'Foxman, Betsy', 'Monto, Arnold S.', 'Baric, Ralph S.', 'Martin, Emily T.', 'Uzicanin, Amra', 'Rainey, Jeanette J.', 'Aiello, Allison E.']",Influenza Other Respir Viruses,,,True
5e0efb6f40dc7f8e441d0569c8b7a86f2bfbc13a,PMC,"Primary care influenza‐like illness surveillance in Ho Chi Minh City, Vietnam 2013‐2015",http://dx.doi.org/10.1111/irv.12574,PMC6086852,29858879,CC BY,"BACKGROUND: Year‐round transmission of influenza has been detected in Vietnam through both national surveillance and other epidemiological studies. Understanding the demographic and clinical features of influenza‐like illness (ILI) presenting to primary care in urban Vietnam is vital to understand these transmission dynamics. METHODS: An observational study of patients with ILI in Ho Chi Minh City, Vietnam, was conducted between August 2013 and November 2015 in a mix of public and private primary care settings. Molecular testing for influenza A and influenza B and 12 other respiratory viruses was performed. RESULTS: A total of 1152 ILI patients were recruited. 322 and 136 subjects tested positive for influenza A and influenza B, respectively. 193 subjects tested positive for another respiratory virus; most commonly rhinovirus and parainfluenza virus 3. Influenza was detected in 81% of the 116 study weeks. Three peaks of influenza activity were detected; an H3N2 peak April‐June 2014, an influenza B peak July‐December 2014, and a mixed H3N2 and H1N1 peak March‐September 2015. Subjects recruited from private clinics were more likely to have higher income and to have reported previous influenza vaccination. Antibiotic use was common (50.3%) despite limited evidence of bacterial infection. CONCLUSION: Influenza in southern Vietnam has complex transmission dynamics including periods of intense influenza activity of alternating types and subtypes. Broadening surveillance from hospital to the community in tropical settings is feasible and a valuable for improving our understanding of the global spread and evolution of the virus.",2018 Sep 7,"['Todd, Stacy', 'Huong, Nguyen Thi Cam', 'Thanh, Nguyen Thi Le', 'Vy, Nguyen Ha Thao', 'Hung, Nguyen Thanh', 'Thao, Tran Thi Nhu', 'Phuong, Huynh Thi', 'van Doorn, Rogier', 'Hang, Vu Thi Ty', 'Chau, Nguyen Van Vinh', 'Read, Jonathan M.', 'Lalloo, David G.', 'Boni, Maciej F.']",Influenza Other Respir Viruses,,,True
6ce3549c42e7ee6246de3eac9ac764f65393ecf8,PMC,"Recovery of pulmonary functions, exercise capacity, and quality of life after pulmonary rehabilitation in survivors of ARDS due to severe influenza A (H1N1) pneumonitis",http://dx.doi.org/10.1111/irv.12566,PMC6086854,29676537,CC BY,"BACKGROUND: Acute respiratory distress syndrome (ARDS) due to severe influenza A H1N1 pneumonitis would result in impaired pulmonary functions and health‐related quality of life (HRQoL) after hospital discharge. OBJECTIVES: The recovery of pulmonary functions, exercise capacity, and HRQoL in the survivors of ARDS due to 2009 pandemic influenza A H1N1 pneumonitis (H1N1‐ARDS) was evaluated in a tertiary teaching hospital in northern Taiwan between May 2010 and June 2011. PATIENTS AND METHODS: Data of spirometry, total lung capacity (TLC), diffusing capacity of carbon monoxide (DL(CO)), and 6‐minute walk distance (6MWD) in the patients survived from H1N1‐ARDS were collected 1, 3, and 6 months post‐hospital discharge. HRQoL was evaluated with St. George respiratory questionnaire (SGRQ). RESULTS: Nine survivors of H1N1‐ARDS in the study period were included. All these patients received 2 months’ pulmonary rehabilitation program. Pulmonary functions and exercise capacity included TLC, forced vital capacity (FVC), forced expiratory volume in the first second (FEV (1)), DL(CO), and 6MWD improved from 1 to 3 months post‐hospital discharge. Only TLC had further significant improvement from 3 to 6 months. HRQoL represented as the total score of SGRQ had no significant improvement in the first 3 months but improved significantly from 3 to 6 months post‐discharge. CONCLUSION: The impaired pulmonary functions and exercise capacity in the survivors of H1N1‐ARDS improved soon at 3 months after hospital discharge. Their quality of life had keeping improved at 6 months even though there was no further improvement of their pulmonary functions and exercise capacity.",2018 Sep 12,"['Hsieh, Meng‐Jer', 'Lee, Wei‐Chun', 'Cho, Hsiu‐Ying', 'Wu, Meng‐Fang', 'Hu, Han‐Chung', 'Kao, Kuo‐Chin', 'Chen, Ning‐Hung', 'Tsai, Ying‐Huang', 'Huang, Chung‐Chi']",Influenza Other Respir Viruses,,,True
de6c34a97fa39dae81dd7f300648f1e6c21c67f6,PMC,T84 air‐liquid interface cultures enable isolation of human bocavirus,http://dx.doi.org/10.1111/irv.12567,PMC6086856,29676538,CC BY,,2018 Sep 8,"['Schildgen, Verena', 'Longo, Ylenia', 'Pieper, Monika', 'Schildgen, Oliver']",Influenza Other Respir Viruses,,,True
0df659d4611fe09f4fa6ef2c22ec087985182ccb,PMC,Programmed cell removal by calreticulin in tissue homeostasis and cancer,http://dx.doi.org/10.1038/s41467-018-05211-7,PMC6086865,30097573,CC BY,"Macrophage-mediated programmed cell removal (PrCR) is a process essential for the clearance of unwanted (damaged, dysfunctional, aged, or harmful) cells. The detection and recognition of appropriate target cells by macrophages is a critical step for successful PrCR, but its molecular mechanisms have not been delineated. Here using the models of tissue turnover, cancer immunosurveillance, and hematopoietic stem cells, we show that unwanted cells such as aging neutrophils and living cancer cells are susceptible to “labeling” by secreted calreticulin (CRT) from macrophages, enabling their clearance through PrCR. Importantly, we identified asialoglycans on the target cells to which CRT binds to regulate PrCR, and the availability of such CRT-binding sites on cancer cells correlated with the prognosis of patients in various malignancies. Our study reveals a general mechanism of target cell recognition by macrophages, which is the key for the removal of unwanted cells by PrCR in physiological and pathophysiological processes.",2018 Aug 10,"['Feng, Mingye', 'Marjon, Kristopher D.', 'Zhu, Fangfang', 'Weissman-Tsukamoto, Rachel', 'Levett, Aaron', 'Sullivan, Katie', 'Kao, Kevin S.', 'Markovic, Maxim', 'Bump, Paul A.', 'Jackson, Hannah M.', 'Choi, Timothy S.', 'Chen, Jing', 'Banuelos, Allison M.', 'Liu, Jie', 'Gip, Phung', 'Cheng, Lei', 'Wang, Denong', 'Weissman, Irving L.']",Nat Commun,,,True
c4c66c993caf42483f4d0a300410ef790f5b07d7,PMC,Programmed cell removal by calreticulin in tissue homeostasis and cancer,http://dx.doi.org/10.1038/s41467-018-05211-7,PMC6086865,30097573,CC BY,"Macrophage-mediated programmed cell removal (PrCR) is a process essential for the clearance of unwanted (damaged, dysfunctional, aged, or harmful) cells. The detection and recognition of appropriate target cells by macrophages is a critical step for successful PrCR, but its molecular mechanisms have not been delineated. Here using the models of tissue turnover, cancer immunosurveillance, and hematopoietic stem cells, we show that unwanted cells such as aging neutrophils and living cancer cells are susceptible to “labeling” by secreted calreticulin (CRT) from macrophages, enabling their clearance through PrCR. Importantly, we identified asialoglycans on the target cells to which CRT binds to regulate PrCR, and the availability of such CRT-binding sites on cancer cells correlated with the prognosis of patients in various malignancies. Our study reveals a general mechanism of target cell recognition by macrophages, which is the key for the removal of unwanted cells by PrCR in physiological and pathophysiological processes.",2018 Aug 10,"['Feng, Mingye', 'Marjon, Kristopher D.', 'Zhu, Fangfang', 'Weissman-Tsukamoto, Rachel', 'Levett, Aaron', 'Sullivan, Katie', 'Kao, Kevin S.', 'Markovic, Maxim', 'Bump, Paul A.', 'Jackson, Hannah M.', 'Choi, Timothy S.', 'Chen, Jing', 'Banuelos, Allison M.', 'Liu, Jie', 'Gip, Phung', 'Cheng, Lei', 'Wang, Denong', 'Weissman, Irving L.']",Nat Commun,,,False
4c16e6d3922d2b800f5f3e2dec0e51b9f7700898,PMC,Programmed cell removal by calreticulin in tissue homeostasis and cancer,http://dx.doi.org/10.1038/s41467-018-05211-7,PMC6086865,30097573,CC BY,"Macrophage-mediated programmed cell removal (PrCR) is a process essential for the clearance of unwanted (damaged, dysfunctional, aged, or harmful) cells. The detection and recognition of appropriate target cells by macrophages is a critical step for successful PrCR, but its molecular mechanisms have not been delineated. Here using the models of tissue turnover, cancer immunosurveillance, and hematopoietic stem cells, we show that unwanted cells such as aging neutrophils and living cancer cells are susceptible to “labeling” by secreted calreticulin (CRT) from macrophages, enabling their clearance through PrCR. Importantly, we identified asialoglycans on the target cells to which CRT binds to regulate PrCR, and the availability of such CRT-binding sites on cancer cells correlated with the prognosis of patients in various malignancies. Our study reveals a general mechanism of target cell recognition by macrophages, which is the key for the removal of unwanted cells by PrCR in physiological and pathophysiological processes.",2018 Aug 10,"['Feng, Mingye', 'Marjon, Kristopher D.', 'Zhu, Fangfang', 'Weissman-Tsukamoto, Rachel', 'Levett, Aaron', 'Sullivan, Katie', 'Kao, Kevin S.', 'Markovic, Maxim', 'Bump, Paul A.', 'Jackson, Hannah M.', 'Choi, Timothy S.', 'Chen, Jing', 'Banuelos, Allison M.', 'Liu, Jie', 'Gip, Phung', 'Cheng, Lei', 'Wang, Denong', 'Weissman, Irving L.']",Nat Commun,,,True
30b4defc3cb6deb9e7b1a2719d0537ca01081159,PMC,The Risk of Cross Infection in the Emergency Department: A Simulation Study,http://dx.doi.org/10.1017/ice.2018.61,PMC6088782,29656720,CC BY,"OBJECTIVES: The risk of cross infection in a busy emergency department (ED) is a serious public health concern, especially in times of pandemic threats. We simulated cross infections due to respiratory diseases spread by large droplets using empirical data on contacts (ie, close-proximity interactions of ≤1m) in an ED to quantify risks due to contact and to examine factors with differential risks associated with them. DESIGN: Prospective study. PARTICIPANTS: Health workers (HCWs) and patients. SETTING: A busy ED. METHODS: Data on contacts between participants were collected over 6 months by observing two 12-hour shifts per week using a radiofrequency identification proximity detection system. We simulated cross infection due to a novel agent across these contacts to determine risks associated with HCW role, chief complaint category, arrival mode, and ED disposition status. RESULTS: Cross-infection risk between HCWs was substantially greater than between patients or between patients and HCWs. Providers had the least risk, followed by nurses, and nonpatient care staff had the most risk. There were no differences by patient chief complaint category. We detected differential risk patterns by arrival mode and by HCW role. Although no differential risk was associated with ED disposition status, 0.1 infections were expected per shift among patients admitted to hospital. CONCLUSION: These simulations demonstrate that, on average, 11 patients who were infected in the ED will be admitted to the hospital over the course of an 8-week local influenza outbreak. These patients are a source of further cross-infection risk once in the hospital. Infect Control Hosp Epidemiol 2018;39:688–693",2018 Jun 16,"['Hertzberg, Vicki Stover', 'Wang, Yuke A.', 'Elon, Lisa K.', 'Lowery-North, Douglas W.']",Infect Control Hosp Epidemiol,,,True
a3436bd86402190ee99045fd5a87c277288d585a,PMC,The importance of dog population contact network structures in rabies transmission,http://dx.doi.org/10.1371/journal.pntd.0006680,PMC6089439,30067733,CC BY,"Canine rabies transmission was interrupted in N’Djaména, Chad, following two mass vaccination campaigns. However, after nine months cases resurged with re-establishment of endemic rabies transmission to pre-intervention levels. Previous analyses investigated district level spatial heterogeneity of vaccination coverage, and dog density; and importation, identifying the latter as the primary factor for rabies resurgence. Here we assess the impact of individual level heterogeneity on outbreak probability, effectiveness of vaccination campaigns and likely time to resurgence after a campaign. Geo-located contact sensors recorded the location and contacts of 237 domestic dogs in N’Djaména over a period of 3.5 days. The contact network data showed that urban dogs are socially related to larger communities and constrained by the urban architecture. We developed a network generation algorithm that extrapolates this empirical contact network to networks of large dog populations and applied it to simulate rabies transmission in N’Djaména. The model predictions aligned well with the rabies incidence data. Using the model we demonstrated, that major outbreaks are prevented when at least 70% of dogs are vaccinated. The probability of a minor outbreak also decreased with increasing vaccination coverage, but reached zero only when coverage was near total. Our results suggest that endemic rabies in N’Djaména may be explained by a series of importations with subsequent minor outbreaks. We show that highly connected dogs hold a critical role in transmission and that targeted vaccination of such dogs would lead to more efficient vaccination campaigns.",2018 Aug 1,"['Laager, Mirjam', 'Mbilo, Céline', 'Madaye, Enos Abdelaziz', 'Naminou, Abakar', 'Léchenne, Monique', 'Tschopp, Aurélie', 'Naïssengar, Service Kemdongarti', 'Smieszek, Timo', 'Zinsstag, Jakob', 'Chitnis, Nakul']",PLoS Negl Trop Dis,,,True
6169ee07d0b0784814f46a6c88f54718f84aafc6,PMC,The importance of dog population contact network structures in rabies transmission,http://dx.doi.org/10.1371/journal.pntd.0006680,PMC6089439,30067733,CC BY,"Canine rabies transmission was interrupted in N’Djaména, Chad, following two mass vaccination campaigns. However, after nine months cases resurged with re-establishment of endemic rabies transmission to pre-intervention levels. Previous analyses investigated district level spatial heterogeneity of vaccination coverage, and dog density; and importation, identifying the latter as the primary factor for rabies resurgence. Here we assess the impact of individual level heterogeneity on outbreak probability, effectiveness of vaccination campaigns and likely time to resurgence after a campaign. Geo-located contact sensors recorded the location and contacts of 237 domestic dogs in N’Djaména over a period of 3.5 days. The contact network data showed that urban dogs are socially related to larger communities and constrained by the urban architecture. We developed a network generation algorithm that extrapolates this empirical contact network to networks of large dog populations and applied it to simulate rabies transmission in N’Djaména. The model predictions aligned well with the rabies incidence data. Using the model we demonstrated, that major outbreaks are prevented when at least 70% of dogs are vaccinated. The probability of a minor outbreak also decreased with increasing vaccination coverage, but reached zero only when coverage was near total. Our results suggest that endemic rabies in N’Djaména may be explained by a series of importations with subsequent minor outbreaks. We show that highly connected dogs hold a critical role in transmission and that targeted vaccination of such dogs would lead to more efficient vaccination campaigns.",2018 Aug 1,"['Laager, Mirjam', 'Mbilo, Céline', 'Madaye, Enos Abdelaziz', 'Naminou, Abakar', 'Léchenne, Monique', 'Tschopp, Aurélie', 'Naïssengar, Service Kemdongarti', 'Smieszek, Timo', 'Zinsstag, Jakob', 'Chitnis, Nakul']",PLoS Negl Trop Dis,,,False
76f9e58fe7a4be360490151b1d2fdeba380c1603,PMC,Severe atypical pneumonia in critically ill patients: a retrospective multicenter study,http://dx.doi.org/10.1186/s13613-018-0429-z,PMC6089852,30105627,CC BY,"BACKGROUND: Chlamydophila pneumoniae (CP) and Mycoplasma pneumoniae (MP) patients could require intensive care unit (ICU) admission for acute respiratory failure. METHODS: Adults admitted between 2000 and 2015 to 20 French ICUs with proven atypical pneumonia were retrospectively described. Patients with MP were compared to Streptococcus pneumoniae (SP) pneumonia patients admitted to ICUs. RESULTS: A total of 104 patients were included, 71 men and 33 women, with a median age of 56 [44–67] years. MP was the causative agent for 76 (73%) patients and CP for 28 (27%) patients. Co-infection was documented for 18 patients (viruses for 8 [47%] patients). Median number of involved quadrants on chest X-ray was 2 [1–4], with alveolar opacities (n = 61, 75%), interstitial opacities (n = 32, 40%). Extra-pulmonary manifestations were present in 34 (33%) patients. Mechanical ventilation was required for 75 (72%) patients and vasopressors for 41 (39%) patients. ICU length of stay was 16.5 [9.5–30.5] days, and 11 (11%) patients died in the ICU. Compared with SP patients, MP patients had more extensive interstitial pneumonia, fewer pleural effusion, and a lower mortality rate [6 (8%) vs. 17 (22%), p = 0.013]. According MCA analysis, some characteristics at admission could discriminate MP and SP. MP was more often associated with hemolytic anemia, abdominal manifestations, and extensive chest radiograph abnormalities. SP-P was associated with shock, confusion, focal crackles, and focal consolidation. CONCLUSION: In this descriptive study of atypical bacterial pneumonia requiring ICU admission, mortality was 11%. The comparison with SP pneumonia identified clinical, laboratory, and radiographic features that may suggest MP or CP pneumonia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13613-018-0429-z) contains supplementary material, which is available to authorized users.",2018 Aug 13,"['Valade, S.', 'Biard, L.', 'Lemiale, V.', 'Argaud, L.', 'Pène, F.', 'Papazian, L.', 'Bruneel, F.', 'Seguin, A.', 'Kouatchet, A.', 'Oziel, J.', 'Rouleau, S.', 'Bele, N.', 'Razazi, K.', 'Lesieur, O.', 'Boissier, F.', 'Megarbane, B.', 'Bigé, N.', 'Brulé, N.', 'Moreau, A. S.', 'Lautrette, A.', 'Peyrony, O.', 'Perez, P.', 'Mayaux, J.', 'Azoulay, E.']",Ann Intensive Care,,,True
57d6bf2cc1fc387a33ba3ff4343e0bbd7a12dfaf,PMC,"Genotypic Diversity and Epidemiology of Human Rhinovirus Among Children With Severe Acute Respiratory Tract Infection in Shanghai, 2013–2015",http://dx.doi.org/10.3389/fmicb.2018.01836,PMC6090050,30131797,CC BY,"Human rhinovirus (HRV), and particularly HRV-C, is increasingly recognized as a cause of severe acute respiratory infections (SARIs). However, little is known about the genotypic diversity and epidemiology of HRV among children with SARI. Thus, we investigated the genotypic diversity and epidemiology of HRV in children with SARI in China over a 2-year period. In total 1,003, nasopharyngeal aspirates were collected from children hospitalized with SARI in Shanghai from 2013 to 2015. HRV was screened for by a PCR method targeting the viral 5′ UTR and was genotyped by sequencing of the VP4–VP2 region of the HRV genome. We also screened for 15 other common respiratory viruses to assess the prevalence of co-infection with HRV. The patient demographic and clinical data were reviewed. HRV was detected in 280 (27.9%) of the 1,003 specimens: HRV-A in 140 (14.0%), HRV-B in 21 (2.1%), HRV-C in 56 (5.6%), and HRV-untyped in 63 (6.3%). A phylogenetic analysis identified 77 genotypes (43 HRV-A, 10 HRV-B, and 24 HRV-C), among which A78, A12, A89, B70, C2, C6, and C24 predominated. HRV-A was detected mainly in winter 2013 and autumn 2014, while HRV-C detection peaked in autumn 2013 and 2014. The detection frequency of HRV-A was highest in patients <5 years old. Most HRV co-infections involved adenovirus, human bocavirus, and/or human respiratory syncytial virus. In conclusion, HRV-A and -C predominate in children with SARI in Shanghai. Among the 77 genotypes detected, A78, A12, A89, B70, C2, C6, and C24 were the most frequent. The HRV species responsible for SARIs differs according to season and age.",2018 Aug 7,"['Zhao, Yanjie', 'Shen, Jun', 'Wu, Bingjie', 'Liu, Gaoshan', 'Lu, Roujian', 'Tan, Wenjie']",Front Microbiol,,,True
0dc51a358655e78b2b47b4bc7c8b240556696a35,PMC,Position Paper on Road Map for RNA Virus Research in India,http://dx.doi.org/10.3389/fmicb.2018.01753,PMC6090158,30131779,CC BY,"The Indian subcontinent with its population density, climatic conditions, means of subsistence, socioeconomic factors as well as travel and tourism presents a fertile ground for thriving of RNA viruses. Despite being pathogens of huge significance, there is very little focus on research into the biology and pathogenesis of RNA viruses in India. Studies on epidemiology and disease burden, risk factors, the immune response to RNA viruses, circulating virus strains and virus evolution, animal models of disease, antivirals and vaccines are strikingly absent. Emerging RNA viruses such as Zika virus, Nipah virus and Crimean-Congo haemorrhagic fever virus are a matter of grave concern to India. Here we summarize the outcome of the India|EMBO symposium on “RNA viruses: immunology, pathogenesis and translational opportunities” organized at Faridabad, National Capital Region, India, on March 28–30, 2018. The meeting focused on RNA viruses (non-HIV), and both national and international experts on RNA viruses covered topics ranging from epidemiology, immune response, virus evolution and vaccine trials concerning RNA viruses. The aim of the symposium was to create a road map for RNA virus research in India. Both concrete and tentative ideas pointing towards short-term and long-term goals were presented with recommendations for follow-up at government level.",2018 Jul 31,"['Medigeshi, Guruprasad R.', 'Fink, Katja', 'Hegde, Nagendra R.']",Front Microbiol,,,True
6d8c165aff79de76522a52da6616f6595fbc1976,PMC,Genetic diversity of BCoV in Brazilian cattle herds,http://dx.doi.org/10.1002/vms3.102,PMC6090412,29687958,CC BY,"Bovine coronavirus (BCoV) is one of the main aetiological agents of gastroenteritis in calves, causing significant economic damage to livestock. This study aims to characterise BCoV genetically on the basis of the N gene. A total of 114 faecal samples from beef and dairy calves with or without clinical symptoms of diarrhoea from five Brazilian states (São Paulo, Minas Gerais, Santa Catarina, Mato Grosso and Bahia) were evaluated between 2008 and 2015 by technique of Semi‐nested RT‐PCR for gene N and genealogical analysis. Of the 114 samples analysed, 14.91% (17/114) were positive. BCoV was detected in 22.72% (10/44) of the animals with diarrhoea and in 10% (7/70) of asymptomatic animals. BCoV was identified in calves from rural properties located in all of the regions sampled. Genealogical analysis showed that the Brazilian sequences of BCoV for the gene which codes for the N protein can be broken down into two distinct clusters, and the samples from this study were closely linked to Asian strains. These results contribute to the molecular characterization of BCoV in Brazil and are the first report of the circulation of BCoV in the states of Santa Catarina and Bahia.",2018 Apr 24,"['de Mira Fernandes, Adeline', 'Brandão, Paulo E.', 'dos Santos Lima, Michele', 'de Souza Nunes Martins, Maira', 'da Silva, Thais G.', 'da Silva Cardoso Pinto, Vivian', 'de Paula, Larissa T.', 'Vicente, Marta Elisabete S.', 'Okuda, Liria H.', 'Pituco, Edviges M.']",Vet Med Sci,,,True
49c210ede22653e57df63a78de1c116b79b518a5,PMC,Dietary supplementation with olive mill wastewaters induces modifications on chicken jejunum epithelial cell transcriptome and modulates jejunum morphology,http://dx.doi.org/10.1186/s12864-018-4962-9,PMC6090849,30068314,CC BY,"BACKGROUND: The Mediterranean diet is considered one of the healthier food habits and olive oil is one of its key components. Olive oil polyphenols are known to induce beneficial effects in several pathological conditions, such as inflammatory bowel disease, and to contrast the proliferation of cancer cells or hypercholesterolemia. Polyphenols are also present in waste products derived from the olive industry: olive mill wastewaters (OMWW) are rich in polyphenols and there is an increasing interest in using OMWW in animal nutrition. OMWW are attributed with positive effects in promoting chicken performance and the quality of food-derived products. However, a tissue-specific transcriptome target analysis of chickens fed with OMWW has never been attempted. RESULTS: We explored the effect of dietary OMWW on the intestinal function in broilers. A morphological analysis of the jejunum revealed that OMWW reduced crypt depth, whereas no significant modifications were observed for villus height and the villus height/crypt depth ratio. An RNA Sequencing analysis was performed on isolated, intestinal, epithelial cells and 280 differentially expressed genes were found using a count-based approach. An enrichment analysis revealed that the majority of up regulated genes in the OMWW group were over-represented by the regulation of viral genome replication-related GO-Terms, whereas down regulated genes were mainly involved in cholesterol and lipid metabolism. CONCLUSIONS: Our study showed how an industrial waste product can be recycled as a feed additive with a positive relapse. OMWW dietary supplementation can be a nutritional strategy to improve chicken performance and health, prevent intestinal damage, enhance innate immunity and regulate cholesterol metabolism and fat deposition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-4962-9) contains supplementary material, which is available to authorized users.",2018 Aug 2,"['Sabino, Marcella', 'Cappelli, Katia', 'Capomaccio, Stefano', 'Pascucci, Luisa', 'Biasato, Ilaria', 'Verini-Supplizi, Andrea', 'Valiani, Andrea', 'Trabalza-Marinucci, Massimo']",BMC Genomics,,,True
15724c0c0f8675d894aa76e25c9a29f4266d0440,PMC,Synergistic Activity of Colistin in Combination With Resveratrol Against Colistin-Resistant Gram-Negative Pathogens,http://dx.doi.org/10.3389/fmicb.2018.01808,PMC6091244,30131787,CC BY,"Objectives: In this study, we investigated the antimicrobial activity of resveratrol in combination with colistin, a last-resort agent for the treatment of severe infections caused by multidrug resistant Gram-negative pathogens. Methods: The synergistic activity and the bactericidal activity of colistin in combination with resveratrol was investigated by checkerboard assays and time-kill assays, respectively. A total of 21 strains were investigated, including 16 strains of different species (Klebsiella pneumoniae, n = 6, Escherichia coli, n = 6; Citrobacter braakii, n = 1; Stenotrophomonas malthophilia, n = 1; Enterobacter cloaceae, n = 1; Acinetobacter baumannii, n = 1) with acquired colistin resistance, three colistin-susceptible K. pneumoniae precursors, and two strains of intrinsically colistin-resistant species (Serratia marcescens, n = 1; Proteus mirabilis, n = 1). Mechanisms of acquired colistin resistance included chromosomal mutations (i.e., mgrB, pmrAB) and plasmid genes (mcr-1, mcr-1.2). Results: Resveratrol did not show any significant intrinsic antimicrobial activity. Overall, a relevant synergistic antimicrobial activity of resveratrol in combination with colistin was observed with all tested strains, except for the three colistin-susceptible K. pneumoniae strains, and for two mcr-1-positive E. coli strains. In time-kill assays, performed with 15 selected strains, the combination of colistin 2 mg/L plus resveratrol 128 mg/L was bactericidal with 11 strains, and bacteriostatic for the remaining ones. Conclusions: Resveratrol was found to potentiate colistin activity against a wide panel of colistin-resistant strains, regardless of species and resistance mechanisms, which would deserve further investigation for potential clinical applications.",2018 Aug 7,"['Cannatelli, Antonio', 'Principato, Silvia', 'Colavecchio, Olga L.', 'Pallecchi, Lucia', 'Rossolini, Gian Maria']",Front Microbiol,,,True
bdb2855fba379ffefbd1e4b49d0d5db65ee93852,PMC,Identification and Validation of Reference Genes for RT-qPCR Normalization in Mythimna separata (Lepidoptera: Noctuidae),http://dx.doi.org/10.1155/2018/1828253,PMC6091413,30151374,CC BY,"Mythimna separata is a major agricultural pest with seasonal migrating trait in China. Formation and regulation mechanism of migration behavior has resulted in a large number of fundamental researches involving quantitative studies of gene expression in this species. Using appropriate reference gene is critical in RT-qPCR data normalization. A comprehensive study on the reference genes in M. separata is lacking. In this paper, expression stabilities of ten candidate reference genes were evaluated in M. separata under various biotic and abiotic conditions by employing four different software geNorm, NormFinder, BestKeeper, and the comparative ΔCT method. The comprehensive stabilities ranking of these genes were suggested by RefFinder. PKG as a target gene was employed to justify the number of reference genes in four larval tissues and two photoperiod treatments. Results demonstrate that the first three most stable genes were as follows: EF, CypA, and β-TUB for developmental stages; EF, CypA, and RPL12 for larval tissues; EF, TBP, and β-TUB for adult tissues. RPL12, β-TUB, and EF for densities; EF, RPL12, and GAPDH for photoperiod treatments; β-TUB, EF, and ATPase for temperature treatments. Stable reference gene combinations may reduce bias in normalization. This work provides for the first time a comprehensive list of appropriate reference genes and facilitates future studies on gene function of M. separata.",2018 Jul 31,"['Li, Ke', 'Xu, Na', 'Yang, Yu Jing', 'Zhang, Jin Hui', 'Yin, Huan']",Biomed Res Int,,,True
5a2e46bae8ee2f620f032cf40f4057963ac7ab03,PMC,Survey on the implementation of the Occupational Health and Safety Act at an academic hospital in Johannesburg,http://dx.doi.org/10.4102/curationis.v39i1.1524,PMC6091593,27796104,CC BY,"BACKGROUND: Despite the available research findings, recommendations and the South African Occupational Health and Safety Act (OHSA) (Act 85 of 1993), there are still challenges with regard to the implementation of selected sections and regulations of the OHSA. This is evidenced by the occupational injuries and illness claims registered with the compensation fund (South Africa, Department of Labour 1993). OBJECTIVES: To determine the extent to which the OHSA was implemented at an academic hospital in Johannesburg, from the senior professional nurses and nursing managers’ perspective, and to describe recommendations in order to facilitate the implementation of the Act. METHODS: A contextual, quantitative, exploratory and descriptive survey was conducted. A purposive sampling method was used to select the participants that met the inclusion criteria. A structured Likert-scale questionnaire was used to collect data (Brink 2011). Stata version 12 was used to analyse the data. Cronbach’s alpha, with a cut-off point of 0.7 was used to test for internal consistency. Ethical considerations were strictly adhered to. Results are presented in the form of graphs, frequency distributions and tables. RESULTS: The study revealed that overall there is 93.3% non-implementation of the selected sections and regulations of the OHSA. These results have serious implications on the health and safety of employees in the workplace. CONCLUSION: The study recommends that the replication of the study should be conducted in order to determine the extent of implementation of the selected sections and regulations of the OHSA in other government institutions.",2016 Sep 28,"['Foromo, Muraga R.', 'Chabeli, Mary', 'Satekge, Mpho M.']",Curationis,,,True
409c387fb844383d955d8a6d7aace1a4d9e40e63,PMC,"Lack of serological evidence of Middle East respiratory syndrome coronavirus infection in virus exposed camel abattoir workers in Nigeria, 2016",http://dx.doi.org/10.2807/1560-7917.ES.2018.23.32.1800175,PMC6092911,30107872,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic threat of global public health concern and dromedary camels are the source of zoonotic infection. Although MERS-CoV is enzootic in dromedaries in Africa as well as the Middle East, zoonotic disease has not been reported in Africa. Methods: In an abattoir in Kano, Nigeria, we tested nasal swabs from camels and investigated 261 humans with repeated occupational exposure to camels, many of whom also reported drinking fresh camel milk (n = 138) or urine (n = 94) or using camel urine for medicinal purposes (n = 96). Results: Weekly MERS-CoV RNA detection in January–February 2016 ranged from 0–8.4% of camels sampled. None of the abattoir workers with exposure to camels had evidence of neutralising antibody to MERS-CoV. Conclusion: There is a need for more studies to investigate whether or not zoonotic transmission of MERS-CoV does take place in Africa.",2018 Aug 9,"['So, Ray TY', 'Perera, Ranawaka APM', 'Oladipo, Jamiu O', 'Chu, Daniel KW', 'Kuranga, Sulyman A', 'Chan, Kin-ho', 'Lau, Eric HY', 'Cheng, Samuel MS', 'Poon, Leo LM', 'Webby, Richard J', 'Peiris, Malik']",Euro Surveill,,,True
52ee7bd3f076b9f68b8fcea6687db4327d99cf71,PMC,Mink (Neovison vison) kits with pre-weaning diarrhea have elevated serum amyloid A levels and intestinal pathomorphological similarities with New Neonatal Porcine Diarrhea Syndrome,http://dx.doi.org/10.1186/s13028-018-0403-7,PMC6094914,30111375,CC BY,"BACKGROUND: Pre-weaning diarrhea (PWD) is a syndrome affecting farm-raised neonatal mink kits. Apart from diarrhea it causes greasy skin exudation, dehydration, and distressed behavior and can ultimately lead to death. No specific causative agents have been identified and the syndrome is regarded as multifactorial. The aim of the present study was to investigate a possible inflammatory state in mink kits with PWD, as indicated by raised serum concentrations of the acute phase protein serum amyloid A (SAA) and by changes in intestinal pathomorphology and intestinal contents of bacteria. Samples collected from 20 diarrheic mink kits with PWD and 20 age-matched non-diarrheic control mink kits from two commercial Danish farms during the pre-weaning period (April–May) in 2016 were analyzed. RESULTS: Concentrations of SAA in serum samples from mink kits with PWD were significantly higher (up to 1000-fold) compared to non-diarrheic control mink kits. Significant features of enterocytic vacuolization, atrophy and fusion of villi in jejunum and mucosal atrophy of the colon of kits with PWD were found. Moreover, attachment of coccoid bacteria to enterocytes was more often found in kits suffering from PWD, while intra-cytoplasmic eosinophil bodies were more frequently observed in control kits. Cellular infiltrations with mononuclear and neutrophil leukocytes were not associated with disease status. Bacteria from the Staphylococcus intermedius group, such as Staphylococcus delphini, were more frequently cultivated from control mink kits, whereas Enterococcus spp. dominated in mink kits with PWD. Escherichia coli was cultivated from both control and mink kits with PWD, but with a higher frequency from mink kits with PWD. CONCLUSION: A significant increase in circulating concentrations of SAA was found in PWD affected mink kits from 6 to 23 days old compared to controls. The histopathological changes in PWD mink kits suggest that the type of diarrhea is secretory. Attachment of coccoid bacteria, therefore, might be responsible for an enterotoxic effect causing a loss of balance in movements of ions and water leading to the vacuolization and swelling of the enterocytes. The slight to moderate infiltrations of neutrophils irrespectively of diarrheic status and the attachment of coccoid bacteria to enterocytes are comparable to observations found in piglets suffering from New Neonatal Porcine Diarrhea Syndrome. Mechanisms behind the correlation between increased SAA levels and the observed pathological intestinal features remain obscure.",2018 Aug 15,"['Mathiesen, Ronja', 'Birch, Julie Melsted', 'Chriél, Mariann', 'Jensen, Henrik Elvang', 'Agger, Jens Frederik', 'Heegaard, Peter Mikael Helweg', 'Struve, Tina']",Acta Vet Scand,,,True
7e988b275962a05ab35cab7441de87933b306a2e,PMC,Zoonotic Diseases and Phytochemical Medicines for Microbial Infections in Veterinary Science: Current State and Future Perspective,http://dx.doi.org/10.3389/fvets.2018.00166,PMC6095004,30140679,CC BY,"Diseases caused by bacterial infections in small-scale and industrial livestock are becoming serious global health concern in veterinary science. Zoonotic bacteria, including Staphylococcus, Campylobacter, and Bartonella species, that infect animals and humans cause various illnesses, such as fever, diarrhea, and related complications. Bacterial diseases in animals can be treated with various classes of antibiotics, including fluoroquinolones, beta-lactams, aminoglycosides, and macrolides. However, the overuse and misuse of antibiotics have led to drug resistance in infectious agents, e.g., methicillin-resistant Staphylococcus; this hampers the treatment of infections in livestock, and such problems are increasing worldwide. Dietary phytochemicals and herbal medicines are useful and viable alternatives to pharmaceuticals because they are economical, effective, non-resistance-forming, renewable, and environmentally friendly. They are small molecules with high structural diversity that cause selective stress to or stimulation of resident microbiota, consequently causing an abundance of such microorganisms; thus, they can be used in preventing various diseases, ranging from metabolic and inflammatory diseases to cancer. In addition, the antioxidant effects of phytochemicals prevent substantial losses in the livestock industry by increasing animal fertility and preventing diseases. Potentially effective plant extracts could be used in combination with antibiotics to decrease the required dose of antibiotics and increase their effectiveness. This strategy can help avoid the side effects of chemical antimicrobials and allow the effective use of phytochemicals for treating diseases. Furthermore, phytochemicals are considered as potential alternatives to antibiotics because of their economical, non-resistance-forming and environmentally friendly properties. Flavonoids such as resveratrol, epigallocatechin gallate, and phenols such as galangin, puerarin, and ursolic acid are proven to be effective as antimicrobial agents. This review provides invaluable information about the types of microbial infections in animals and the current knowledge on phytotherapeutic agents classified by their mode of actions. It also provides insights into potential strategies for effectively treating animal infections using phytochemicals.",2018 Jul 24,"['Shin, Bora', 'Park, Woojun']",Front Vet Sci,,,True
82e479c9e81790fa8a0dc356b36d389616bf7bad,PMC,"Hajj, Umrah, and the neglected tropical diseases",http://dx.doi.org/10.1371/journal.pntd.0006539,PMC6095481,30114210,CC BY,,2018 Aug 16,"['Almutairi, Mashal M.', 'Alsalem, Waleed Saleh', 'Hassanain, Mazen', 'Hotez, Peter J.']",PLoS Negl Trop Dis,,,True
a85c514ecb1b99f55aafe306a5f3351d231a4de2,PMC,cGAS and STING: At the intersection of DNA and RNA virus-sensing networks,http://dx.doi.org/10.1371/journal.ppat.1007148,PMC6095619,30114241,CC BY,,2018 Aug 16,"['Ni, Guoxin', 'Ma, Zhe', 'Damania, Blossom']",PLoS Pathog,,,True
30215fe783662edff46565307706587b3bdd60a5,PMC,CD4 T(RM) Cells Following Infection and Immunization: Implications for More Effective Vaccine Design,http://dx.doi.org/10.3389/fimmu.2018.01860,PMC6095996,30147701,CC BY,"The induction of immunological memory, which is mediated by memory T and B cells, is central to adaptive protective immunity to pathogens induced by previous infection and is the cornerstone of effective vaccine design. Recent studies in mice have suggested that memory T cells that accumulate in tissues, termed tissue-resident memory T (T(RM)) cells, play a crucial role in maintaining long-term protective immunity to mucosal pathogens. CD4 and CD8 T(RM) cells can be induced following infection at mucosal sites or the skin, where they are maintained and poised to respond rapidly to reinfection with the same pathogen. T(RM) cells can also be generated by vaccination, but their induction is influenced by a number of factors, including the type of vaccine, the adjuvant, and the route of immunization. Live attenuated vaccines appear to be more effective than killed or subunit vaccines at inducing T(RM) cells and mucosal immunization, especially by intranasal route, is more effective than parenteral delivery. However, evidence is emerging that formulation of killed or subunit vaccines with novel adjuvants, especially those that generate Th1 and Th17 responses, can promote the induction of T(RM) cells. While T(RM) cells are also present at high number in mucosal tissues in humans, one of the challenge will be to develop methodologies for routine quantification of these cells in humans. Nevertheless, the identification of approaches for optimum induction of T(RM) cells in mice should assist in the design of more effective vaccines that sustain protective immunity against a range of human pathogens.",2018 Aug 10,"['Wilk, Mieszko M.', 'Mills, Kingston H. G.']",Front Immunol,,,True
6cabb9dc94d381013cd38885a5f0af29490c74f6,PMC,Microglia control the spread of neurotropic virus infection via P2Y12 signalling and recruit monocytes through P2Y12-independent mechanisms,http://dx.doi.org/10.1007/s00401-018-1885-0,PMC6096730,30027450,CC BY,"Neurotropic herpesviruses can establish lifelong infection in humans and contribute to severe diseases including encephalitis and neurodegeneration. However, the mechanisms through which the brain’s immune system recognizes and controls viral infections propagating across synaptically linked neuronal circuits have remained unclear. Using a well-established model of alphaherpesvirus infection that reaches the brain exclusively via retrograde transsynaptic spread from the periphery, and in vivo two-photon imaging combined with high resolution microscopy, we show that microglia are recruited to and isolate infected neurons within hours. Selective elimination of microglia results in a marked increase in the spread of infection and egress of viral particles into the brain parenchyma, which are associated with diverse neurological symptoms. Microglia recruitment and clearance of infected cells require cell-autonomous P2Y12 signalling in microglia, triggered by nucleotides released from affected neurons. In turn, we identify microglia as key contributors to monocyte recruitment into the inflamed brain, which process is largely independent of P2Y12. P2Y12-positive microglia are also recruited to infected neurons in the human brain during viral encephalitis and both microglial responses and leukocyte numbers correlate with the severity of infection. Thus, our data identify a key role for microglial P2Y12 in defence against neurotropic viruses, whilst P2Y12-independent actions of microglia may contribute to neuroinflammation by facilitating monocyte recruitment to the sites of infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1885-0) contains supplementary material, which is available to authorized users.",2018 Jul 19,"['Fekete, Rebeka', 'Cserép, Csaba', 'Lénárt, Nikolett', 'Tóth, Krisztina', 'Orsolits, Barbara', 'Martinecz, Bernadett', 'Méhes, Előd', 'Szabó, Bálint', 'Németh, Valéria', 'Gönci, Balázs', 'Sperlágh, Beáta', 'Boldogkői, Zsolt', 'Kittel, Ágnes', 'Baranyi, Mária', 'Ferenczi, Szilamér', 'Kovács, Krisztina', 'Szalay, Gergely', 'Rózsa, Balázs', 'Webb, Connor', 'Kovacs, Gabor G.', 'Hortobágyi, Tibor', 'West, Brian L.', 'Környei, Zsuzsanna', 'Dénes, Ádám']",Acta Neuropathol,,,True
7421d0a5937f6e1ec30547de88bc4b4148725995,PMC,Microglia control the spread of neurotropic virus infection via P2Y12 signalling and recruit monocytes through P2Y12-independent mechanisms,http://dx.doi.org/10.1007/s00401-018-1885-0,PMC6096730,30027450,CC BY,"Neurotropic herpesviruses can establish lifelong infection in humans and contribute to severe diseases including encephalitis and neurodegeneration. However, the mechanisms through which the brain’s immune system recognizes and controls viral infections propagating across synaptically linked neuronal circuits have remained unclear. Using a well-established model of alphaherpesvirus infection that reaches the brain exclusively via retrograde transsynaptic spread from the periphery, and in vivo two-photon imaging combined with high resolution microscopy, we show that microglia are recruited to and isolate infected neurons within hours. Selective elimination of microglia results in a marked increase in the spread of infection and egress of viral particles into the brain parenchyma, which are associated with diverse neurological symptoms. Microglia recruitment and clearance of infected cells require cell-autonomous P2Y12 signalling in microglia, triggered by nucleotides released from affected neurons. In turn, we identify microglia as key contributors to monocyte recruitment into the inflamed brain, which process is largely independent of P2Y12. P2Y12-positive microglia are also recruited to infected neurons in the human brain during viral encephalitis and both microglial responses and leukocyte numbers correlate with the severity of infection. Thus, our data identify a key role for microglial P2Y12 in defence against neurotropic viruses, whilst P2Y12-independent actions of microglia may contribute to neuroinflammation by facilitating monocyte recruitment to the sites of infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1885-0) contains supplementary material, which is available to authorized users.",2018 Jul 19,"['Fekete, Rebeka', 'Cserép, Csaba', 'Lénárt, Nikolett', 'Tóth, Krisztina', 'Orsolits, Barbara', 'Martinecz, Bernadett', 'Méhes, Előd', 'Szabó, Bálint', 'Németh, Valéria', 'Gönci, Balázs', 'Sperlágh, Beáta', 'Boldogkői, Zsolt', 'Kittel, Ágnes', 'Baranyi, Mária', 'Ferenczi, Szilamér', 'Kovács, Krisztina', 'Szalay, Gergely', 'Rózsa, Balázs', 'Webb, Connor', 'Kovacs, Gabor G.', 'Hortobágyi, Tibor', 'West, Brian L.', 'Környei, Zsuzsanna', 'Dénes, Ádám']",Acta Neuropathol,,,True
daaa53a49dc0d23015e22a150495ac657aa993d8,PMC,Transcriptional and Translational Landscape of Equine Torovirus,http://dx.doi.org/10.1128/JVI.00589-18,PMC6096809,29950409,CC BY,"The genus Torovirus (subfamily Torovirinae, family Coronaviridae, order Nidovirales) encompasses a range of species that infect domestic ungulates, including cattle, sheep, goats, pigs, and horses, causing an acute self-limiting gastroenteritis. Using the prototype species equine torovirus (EToV), we performed parallel RNA sequencing (RNA-seq) and ribosome profiling (Ribo-seq) to analyze the relative expression levels of the known torovirus proteins and transcripts, chimeric sequences produced via discontinuous RNA synthesis (a characteristic of the nidovirus replication cycle), and changes in host transcription and translation as a result of EToV infection. RNA sequencing confirmed that EToV utilizes a unique combination of discontinuous and nondiscontinuous RNA synthesis to produce its subgenomic RNAs (sgRNAs); indeed, we identified transcripts arising from both mechanisms that would result in sgRNAs encoding the nucleocapsid. Our ribosome profiling analysis revealed that ribosomes efficiently translate two novel CUG-initiated open reading frames (ORFs), located within the so-called 5′ untranslated region. We have termed the resulting proteins U1 and U2. Comparative genomic analysis confirmed that these ORFs are conserved across all available torovirus sequences, and the inferred amino acid sequences are subject to purifying selection, indicating that U1 and U2 are functionally relevant. This study provides the first high-resolution analysis of transcription and translation in this neglected group of livestock pathogens. IMPORTANCE Toroviruses infect cattle, goats, pigs, and horses worldwide and can cause gastrointestinal disease. There is no treatment or vaccine, and their ability to spill over into humans has not been assessed. These viruses are related to important human pathogens, including severe acute respiratory syndrome (SARS) coronavirus, and they share some common features; however, the mechanism that they use to produce sgRNA molecules differs. Here, we performed deep sequencing to determine how equine torovirus produces sgRNAs. In doing so, we also identified two previously unknown open reading frames “hidden” within the genome. Together these results highlight the similarities and differences between this domestic animal virus and related pathogens of humans and livestock.",2018 Aug 16,"['Stewart, Hazel', 'Brown, Katherine', 'Dinan, Adam M.', 'Irigoyen, Nerea', 'Snijder, Eric J.', 'Firth, Andrew E.']",J Virol,,,True
5b80e43b1261e5998412a0976e64cabb01c8b121,PMC,Rapid Identification of Seven Waterborne Exophiala Species by RCA DNA Padlock Probes,http://dx.doi.org/10.1007/s11046-018-0256-7,PMC6096892,29504057,CC BY,"The black yeast genus Exophiala includes numerous potential opportunistic species that potentially cause systematic and disseminated infections in immunocompetent individuals. Species causing systemic disease have ability to grow at 37–40 °C, while others consistently lack thermotolerance and are involved in diseases of cold-blooded, waterborne vertebrates and occasionally invertebrates. We explain a fast and sensitive assay for recognition and identification of waterborne Exophiala species without sequencing. The ITS rDNA region of seven Exophiala species (E. equina, E. salmonis, E. opportunistica, E. pisciphila, E. aquamarina, E. angulospora and E. castellanii) along with the close relative Veronaea botryosa was sequenced and aligned for the design of specific padlock probes for the detection of characteristic single-nucleotide polymorphisms. The assay demonstrated to successfully amplify DNA of target fungi, allowing detection at the species level. Amplification products were visualized on 1% agarose gels to confirm specificity of probe–template binding. Amounts of reagents were reduced to prevent the generation of false positive results. The simplicity, tenderness, robustness and low expenses provide padlock probe assay (RCA) a definite place as a very practical method among isothermal approaches for DNA diagnostics.",2018 Mar 5,"['Najafzadeh, M. J.', 'Vicente, V. A.', 'Feng, Peiying', 'Naseri, A.', 'Sun, Jiufeng', 'Rezaei-Matehkolaei, A.', 'de Hoog, G. S.']",Mycopathologia,,,True
00c88aab2bfcca0db253c972382e5eee245d071e,PMC,Production of complex viral glycoproteins in plants as vaccine immunogens,http://dx.doi.org/10.1111/pbi.12963,PMC6097131,29890031,CC BY,"Plant molecular farming offers a cost‐effective and scalable approach to the expression of recombinant proteins which has been proposed as an alternative to conventional production platforms for developing countries. In recent years, numerous proofs of concept have established that plants can produce biologically active recombinant proteins and immunologically relevant vaccine antigens that are comparable to those made in conventional expression systems. Driving many of these advances is the remarkable plasticity of the plant proteome which enables extensive engineering of the host cell, as well as the development of improved expression vectors facilitating higher levels of protein production. To date, the only plant‐derived viral glycoprotein to be tested in humans is the influenza haemagglutinin which expresses at ~50 mg/kg. However, many other viral glycoproteins that have potential as vaccine immunogens only accumulate at low levels in planta. A critical consideration for the production of many of these proteins in heterologous expression systems is the complexity of post‐translational modifications, such as control of folding, glycosylation and disulphide bridging, which is required to reproduce the native glycoprotein structure. In this review, we will address potential shortcomings of plant expression systems and discuss strategies to optimally exploit the technology for the production of immunologically relevant and structurally authentic glycoproteins for use as vaccine immunogens.",2018 Sep 6,"['Margolin, Emmanuel', 'Chapman, Ros', 'Williamson, Anna‐Lise', 'Rybicki, Edward P.', 'Meyers, Ann E.']",Plant Biotechnol J,,,True
97b03849d178cb08d39be44ebab0a2aa41b6a4d3,PMC,Oral administration of inactivated porcine epidemic diarrhea virus activate DCs in porcine Peyer’s patches,http://dx.doi.org/10.1186/s12917-018-1568-z,PMC6097195,30115049,CC BY,"BACKGROUND: Peyer’s patches (PPs) can be considered as the immune site of the intestine. Within PPs, Dendritic cells (DCs) can uptake antigens from the gut lumen by extending dendrites into epithelium, and process it and then present to lymphocytes, which effectively antigen produces an immune response. Porcine epidemic diarrhea virus (PEDV) is the causative agent of porcine epidemic diarrhea (PED), an acute and highly contagious enteric viral disease. The interaction between inactivated porcine epidemic diarrhea virus and porcine monocyte-derived dendritic cells (Mo-DCs) has been reported. However, little is known about the interaction between inactivated PEDV and DCs in porcine PPs. RESULTS: In this study, for the first time we investigated the role of DCs in porcine PPs after oral administration inactivated PEDV. Firstly, a method to isolate DCs from porcine PPs was established, in which the purity of SWC3a(+)/MHC-II(+) DCs was more than 90%. Our findings clearly indicate that DCs in porcine PPs after oral administration of inactivated PEDV not only stimulated the proliferation of allogeneic lymphocytes, but also secreted cytokines (IL-1, IL-4). Furthermore, the number of DCs and IgA(+) cells in porcine intestinal mucosal significantly increased and the levels of anti-PEDV specific IgG antibody in the serum and SIgA antibody in the feces increased after oral administration inactivated PEDV. CONCLUSIONS: Our findings indicate that oral administration of inactivated PEDV activate DCs in porcine Peyer’s patches and inactivated PEDV may be a useful and safe vaccine to trigger adaptive immunity.",2018 Aug 16,"['Yuan, Chen', 'Zhang, En', 'Huang, Lulu', 'Wang, Jialu', 'Yang, Qian']",BMC Vet Res,,,True
36c9f0d81abca39d9decec0de264ad9b5e8be161,PMC,Diagnostics of rare disorders: whole-exome sequencing deciphering locus heterogeneity in telomere biology disorders,http://dx.doi.org/10.1186/s13023-018-0864-9,PMC6097299,30115091,CC BY,"BACKGROUND: The telomere biology disorders (TBDs) include a range of multisystem diseases characterized by mucocutaneous symptoms and bone marrow failure. In dyskeratosis congenita (DKC), the clinical features of TBDs stem from the depletion of crucial stem cell populations in highly proliferative tissues, resulting from abnormal telomerase function. Due to the wide spectrum of clinical presentations and lack of a conclusive laboratory test it may be challenging to reach a clinical diagnosis, especially if patients lack the pathognomonic clinical features of TBDs. METHODS: Clinical sequencing was performed on a cohort of patients presenting with variable immune phenotypes lacking molecular diagnoses. Hypothesis-free whole-exome sequencing (WES) was selected in the absence of compelling diagnostic hints in patients with variable immunological and haematological conditions. RESULTS: In four patients belonging to three families, we have detected five novel variants in known TBD-causing genes (DKC1, TERT and RTEL1). In addition to the molecular findings, they all presented shortened blood cell telomeres. These findings are consistent with the displayed TBD phenotypes, addressing towards the molecular diagnosis and subsequent clinical follow-up of the patients. CONCLUSIONS: Our results strongly support the utility of WES-based approaches for routine genetic diagnostics of TBD patients with heterogeneous or atypical clinical presentation who otherwise might remain undiagnosed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13023-018-0864-9) contains supplementary material, which is available to authorized users.",2018 Aug 17,"['Trotta, Luca', 'Norberg, Anna', 'Taskinen, Mervi', 'Béziat, Vivien', 'Degerman, Sofie', 'Wartiovaara-Kautto, Ulla', 'Välimaa, Hannamari', 'Jahnukainen, Kirsi', 'Casanova, Jean-Laurent', 'Seppänen, Mikko', 'Saarela, Janna', 'Koskenvuo, Minna', 'Martelius, Timi']",Orphanet J Rare Dis,,,True
1d39fce3c09c95c13c9b8e18c1ab9a85c24ff7c6,PMC,Enhanced pathogenicity of low-pathogenic H9N2 avian influenza virus after vaccination with infectious bronchitis live attenuated vaccine,http://dx.doi.org/10.14202/vetworld.2018.977-985,PMC6097558,30147269,CC BY,"AIM: In the present study, two experiments were carried out for studying the pathogenicity of H9N2 avian influenza virus (AIV) in broiler chickens after vaccination with different live respiratory viral vaccines. MATERIALS AND METHODS: One-day-old specific pathogen-free (SPF) chicks were divided into four groups in each experiment. In experiment 1, Groups 1 and 2 were inoculated with H9N2 AIV through nasal route in 1 day old, Groups 1 and 3 were vaccinated with live infectious bronchitis coronavirus (IBV) vaccine in 5 days old, and Group 4 was left as a negative control. In experiment 2, Groups 5 and 6 were inoculated with AIV subtype H9N2 through nasal route in 1 day old, Group 5 was vaccinated with live IBV vaccine and live Newcastle disease virus (NDV) vaccine in 5 and 18 days old, respectively, Groups 6 and 7 were vaccinated with live NDV vaccine in 18 days old, and Group 8 was left as a negative control. Chicks were kept in isolators for 18 days in the first experiment and 35 days in the second experiment. Tracheal and cloacal swabs were collected from 3, 5, 7, 10, 12, and 15 day’s old chicks from all groups in experiment 1 and 21, 23, 25, and 28 days old from all groups in experiment 2. Quantitative real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) was applied on the collected tracheal swabs for detecting RNA copies of H9N2 AIV. Cloacal swabs and the positive rRT-PCR tracheal swabs were inoculated in 10-day-old SPF embryonated chicken eggs (ECE) to confirm rRT-PCR results. Internal organs (kidney, trachea, and spleen) from all chicken groups were collected weekly for histopathological examination to determine severity of the lesions. Serum samples were collected on a weekly basis for the detection of humoral immune response against H9N2, NDV, and IBV from all chicken groups. RESULTS: rRT-PCR results with virus titration in ECEs revealed a significant increase in H9N2 AIV titer with extension in the period of viral shedding in Groups 1 and 5. Severe lesion score was observed for Groups 1 and 5. The humoral immune response against H9N2 AIV, NDV, and IBV revealed a significant increase in H9N2 AIV titer in Groups 1 and 5, NDV titer showed a significant increase in Group 7, and IBV titer increased in Groups 1, 3, and 5. CONCLUSION: Results demonstrated the increase in pathogenicity of H9N2 AIV, especially when H9N2-infected chicks vaccinated with live IBV vaccine.",2018 Jul 24,"['Ismail, Zainab Mohamed', 'EL-Deeb, Ayman Hanea', 'EL-Safty, Mounir Mohamed', 'Hussein, Hussein Aly']",Vet World,,,True
b4236b54e869414c7cb19814dc2e6216a9573c0e,PMC,Bird feathers as potential sources of pathogenic microorganisms: a new look at old diseases,http://dx.doi.org/10.1007/s10482-018-1048-2,PMC6097735,29460207,CC BY,"This article describes methods of treatment for avian zoonoses, modern antibiotic therapy and drug resistance of selected pathogens, which pose a threat to the population’s health. A tabular form has been used to present the current data from the European Union from 2011 to 2017 regarding human morbidity and mortality and the costs incurred by national health systems for the treatment of zoonoses occurring in humans and animals. Moreover, the paper includes descriptions of selected diseases, which indirectly affect birds. Scientists can obtain information regarding the occurrence of particular diseases, their aetiology, epidemiology, incubation period and symptoms caused by dangerous microorganisms and parasites. This information should be of particular interest for people who have frequent contact with birds, such as ornithologists, as well as veterinarians, farm staff, owners of accompanying animals and zoological workers. This paper presents a review used for identification and genetic characterization of bacterial strains isolated from a variety of environmental sources, e.g., bird feathers along with their practical application. We describe the bacterial, viral and fungal serotypes present on avian feathers after the slaughter process. This review also enables us to effectively identify several of the early stages of infectious diseases from heterogeneous avian research material.",2018 Feb 19,"['Miskiewicz, Andrzej', 'Kowalczyk, Paweł', 'Oraibi, Sanaa Mahdi', 'Cybulska, Krystyna', 'Misiewicz, Anna']",Antonie Van Leeuwenhoek,,,True
2c5f5500b79b97672aca47a26df7996390c30459,PMC,The utility of delta neutrophil index in differentiation of pulmonary tuberculosis from community acquired pneumonia,http://dx.doi.org/10.1038/s41598-018-30967-9,PMC6098156,30120386,CC BY,"No data exist on the usefulness of the delta neutrophil index (DNI) to discriminate pulmonary tuberculosis (PTB) from community-acquired pneumonia (CAP). We performed a retrospective cohort study involving patients with PTB (n = 62) and CAP (n = 215), and compared their initial DNI levels. The median DNI values were 0% (interquartile ranges [IQR] 0–0.2%) and 1.6% (IQR 0.7–2.9%) in PTB and CAP, respectively, which was significantly lower in PTB patients (P < 0.001). Sixty-nine percent of patients with PTB had DNI value of 0%; however, only 15% of patients with CAP had 0% DNI. The discriminatory power of the DNI for diagnosing PTB was high with 89% sensitivity and 67% specificity at a DNI cut-off ≤ 1.0% (area under the curve, 0.852). The diagnostic sensitivity and negative predictive value (NPV) for PTB were 89% (55/62) and 95% (145/152) at the DNI cut-off ≤ 1.0%, respectively, and in multivariate analyses after adjusting for other factors (smoking, no fever, upper lobe involvement), DNI ≤ 1.0% remained significant (odds ratio, 15.265; P < 0.001). We demonstrated that the DNI was lower in PTB compared with CAP, and an initially elevated DNI (>1.0%) may be useful to rule out the possibility of PTB due to its high NPV.",2018 Aug 17,"['Jhun, Byung Woo', 'Sim, Yun Su', 'Shin, Tae Rim', 'Kim, Dong-Gyu']",Sci Rep,,,True
6a68e3a345d7da33f2fcb9456aca1998647cb69e,PMC,Seventy-two-hour emergency department revisits among adults with chronic diseases: a Saudi Arabian study,http://dx.doi.org/10.2147/TCRM.S168763,PMC6098417,30147326,CC BY,"BACKGROUND: Despite the increase in adult emergency department (ED) utilization in Saudi Arabia, no studies have evaluated the 72-hour revisits. This study estimates the rate of 72-hour ED revisits and identifies its reasons and predictive factors among adults with chronic diseases. PATIENTS AND METHODS: A hospital-based retrospective study that included 24,206 ED discharges for adults with chronic diseases at the adult ED of King Abdulaziz Medical City, Riyadh between September 13, 2015 and July 29, 2017 was performed. We extracted data on demographic information, reasons for ED visits/revisits, health insurance coverage, weekend ED arrival, and mortality. RESULTS: A sample of 24,206 ED discharges for 19,697 adults with at least one chronic disease was included in the analysis. The rate of 72-hour revisits in this study population was high: 3,144/24,206 (13%) had the first revisit and 319/3,144 (10.1%) had the second ED revisit within 72 hours. Diseases of the circulatory (19%) and genitourinary (15.8%) systems were the major reasons for the first ED revisit. The adjusted relative rate (aRR) of 72-hour ED revisits was higher in adults with chronic diseases and aged ≥60 years (aRR=1.360, 95% CI: 1.41–1.83; P=0.001), patients of female gender (aRR=1.24, 95% CI: 1.09–1.41; P=0.001), patients with health insurance coverage (aRR=4.23, 95% CI: 2.60–6.90; P=0.001), patients arriving to ED on a weekend (aRR=2.13, 95% CI: 1.03–4.41; P=0.041), and new patients (aRR=1.47, 95% CI: 1.25–1.73; P=0.001). CONCLUSION: The rate of 72-hour revisits is high among adults with chronic diseases. Advancing age, female gender, health insurance coverage, weekend ED arrival, and new patients are the important predictive factors of the high rate of 72-hour revisits. Continuous quality assessment and monitoring of factors related to patients are needed to reduce the frequency of early ED revisits after discharge.",2018 Aug 14,"['Ahmed, Anwar E', 'AlBuraikan, Doaa A', 'Almazroa, Hend R', 'Alrajhi, Manair N', 'ALMuqbil, Bashayr I', 'Albaijan, Monirah A', 'Alsalamah, Majid A', 'AL-Jahdali, Hamdan']",Ther Clin Risk Manag,,,True
e37ede300a3a671cb392f6a06e5b5e0af6e34fd9,PMC,Combining New Non-Nucleoside Reverse Transcriptase Inhibitors (RTIs) with AZT Results in Strong Synergism against Multi-RTI-Resistant HIV-1 Strains,http://dx.doi.org/10.3390/molecules23071599,PMC6099689,30004408,CC BY,"Reverse transcriptase inhibitors (RTIs), including nucleoside RTIs (NRTIs) and non-nucleoside RTIs (NNRTIs), are critical antiretroviral drugs for the treatment of human immunodeficiency virus (HIV) infection. Emergence of multi-RTI resistance calls for the development of more potent therapeutics or regimens against RTI-resistant strains. Here, we demonstrated that combining azidothymidine (AZT) with a new NNRTIs under development, diarylpyridine (DAPA)-2e, diarylanilin (DAAN)-14h, or DAAN-15h, resulted in strong synergism against infection by divergent HIV-1 strains, including those resistant to NRTIs and NNRTIs, suggesting the potential for developing these novel NNRTIs as salvage therapy for HIV/acquired immune deficiency syndrome (AIDS) patients.",2018 Jul 2,"['Yu, Fei', 'Li, Wen', 'Wang, Lili', 'Dai, Yu', 'Lu, Xin', 'Wang, Qian', 'Xie, Lan', 'Jiang, Shibo']",Molecules,,,True
53889c98bb5e342ae879f4e67c3b4c6368389716,PMC,Recent Reports of Solid-Phase Cyclohexapeptide Synthesis and Applications,http://dx.doi.org/10.3390/molecules23061475,PMC6100019,29912160,CC BY,"Macrocyclic peptides are privileged scaffolds for drug development and constitute a significant portion of macrocyclic drugs on the market today in fields spanning from infectious disease to oncology. Developing orally bioavailable peptide-based drugs remains a challenging task; however, macrocyclization of linear peptides can be an effective strategy to improve membrane permeability, proteolytic stability, oral bioavailability, and overall drug-like characteristics for this class. Significant advances in solid-phase peptide synthesis (SPPS) have enabled the efficient construction of macrocyclic peptide and peptidomimetic libraries with macrolactamization being performed on-resin or in solution phase. The primary goal of this review is to summarize solid-phase cyclohexapeptide synthesis using the on-resin and solution-phase macrocyclization methodologies published since 2013. We also highlight their broad applications ranging from natural product total synthesis, synthetic methodology development, and medicinal chemistry, to drug development and analyses of conformational and physiochemical properties.",2018 Jun 18,"['Prior, Allan M.', 'Hori, Taylor', 'Fishman, Ashriel', 'Sun, Dianqing']",Molecules,,,True
5676dd53889b4c43a772e163763ee7f1525f98da,PMC,Separation and Quantification of Four Main Chiral Glucosinolates in Radix Isatidis and Its Granules Using High-Performance Liquid Chromatography/Diode Array Detector Coupled with Circular Dichroism Detection,http://dx.doi.org/10.3390/molecules23061305,PMC6100438,29844266,CC BY,"As chemical drugs, separation and quantification of the specific enantiomer from the chiral compounds in herbal medicines are becoming more important. To clarify the chemical characterization of chiral glucosinolates—the antiviral active ingredients of Radix Isatidis, an optimized efficient method of HPLC-UV-CD was developed to simultaneously separate and quantify the four main chiral glucosinolates: progoitrin, epiprogoitrin, and R,S-goitrin. The first step was to determine progoitrin, epiprogoitrin, and R,S-goitrin using HPLC-UV, and then determine the R-goitrin and S-goitrin by coupling with CD detection. Subsequently, through the linear relations between anisotropy factor (g factor) and the percent optical purity of R-goitrin, the contents of R-goitrin and S-goitrin from the R,S-goitrin mixture were calculated separately. Furthermore, the chemical composition features of the four chiral glucosinolates in 37 samples from crude drugs, decoction pieces, and granules of R. Isatidis were conducted. The total content of the four glucosinolates was obviously higher in crude drugs, and the variance character of each glucosinolate contents was different. In summary, the accurate measurement method reported here allows for better control of the internal quality of R. Isatidis and its granules and provides a powerful approach for the analysis of other chiral components in traditional Chinese medicines.",2018 May 29,"['Shi, Yanhong', 'Zheng, Cheng', 'Li, Jinhang', 'Yang, Li', 'Wang, Zhengtao', 'Wang, Rui']",Molecules,,,True
ff81f65bce47ed0a1a6e586dc196c6543e97d861,PMC,Asymmetric Primaquine and Halogenaniline Fumardiamides as Novel Biologically Active Michael Acceptors,http://dx.doi.org/10.3390/molecules23071724,PMC6100582,30011922,CC BY,"Novel primaquine (PQ) and halogenaniline asymmetric fumardiamides 4a–f, potential Michael acceptors, and their reduced analogues succindiamides 5a–f were prepared by simple three-step reactions: coupling reaction between PQ and mono-ethyl fumarate (1a) or mono-methyl succinate (1b), hydrolysis of PQ-dicarboxylic acid mono-ester conjugates 2a,b to corresponding acids 3a,b, and a coupling reaction with halogenanilines. 1-[bis(Dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) was used as a coupling reagent along with Hünig′s base. Compounds 4 and 5 were evaluated against a panel of bacteria, several Mycobacterium strains, fungi, a set of viruses, and nine different human tumor cell lines. p-Chlorofumardiamide 4d showed significant activity against Staphylococcus aureus, Streptococcus pneumoniae and Acinetobacter baumannii, but also against Candida albicans (minimum inhibitory concentration (MIC) 6.1–12.5 µg/mL). Together with p-fluoro and p-CF(3) fumardiamides 4b,f, compound 4d showed activity against Mycobacterium marinum and 4b,f against M. tuberculosis. In biofilm eradication assay, most of the bacteria, particularly S. aureus, showed susceptibility to fumardiamides. m-CF(3) and m-chloroaniline fumardiamides 4e and 4c showed significant antiviral activity against reovirus-1, sindbis virus and Punta Toro virus (EC(50) = 3.1–5.5 µM), while 4e was active against coxsackie virus B4 (EC(50) = 3.1 µM). m-Fluoro derivative 4a exerted significant cytostatic activity (IC(50) = 5.7–31.2 μM). Acute lymphoblastic leukemia cells were highly susceptible towards m-substituted derivatives 4a,c,e (IC(50) = 6.7–8.9 μM). Biological evaluations revealed that fumardiamides 4 were more active than succindiamides 5 indicating importance of Michael conjugated system.",2018 Jul 14,"['Rajić, Zrinka', 'Beus, Maja', 'Michnová, Hana', 'Vlainić, Josipa', 'Persoons, Leentje', 'Kosalec, Ivan', 'Jampílek, Josef', 'Schols, Dominique', 'Keser, Toma', 'Zorc, Branka']",Molecules,,,True
eb19506b44912be8a9c4b88407adc3e5ebb850fb,PMC,Asymmetric Primaquine and Halogenaniline Fumardiamides as Novel Biologically Active Michael Acceptors,http://dx.doi.org/10.3390/molecules23071724,PMC6100582,30011922,CC BY,"Novel primaquine (PQ) and halogenaniline asymmetric fumardiamides 4a–f, potential Michael acceptors, and their reduced analogues succindiamides 5a–f were prepared by simple three-step reactions: coupling reaction between PQ and mono-ethyl fumarate (1a) or mono-methyl succinate (1b), hydrolysis of PQ-dicarboxylic acid mono-ester conjugates 2a,b to corresponding acids 3a,b, and a coupling reaction with halogenanilines. 1-[bis(Dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) was used as a coupling reagent along with Hünig′s base. Compounds 4 and 5 were evaluated against a panel of bacteria, several Mycobacterium strains, fungi, a set of viruses, and nine different human tumor cell lines. p-Chlorofumardiamide 4d showed significant activity against Staphylococcus aureus, Streptococcus pneumoniae and Acinetobacter baumannii, but also against Candida albicans (minimum inhibitory concentration (MIC) 6.1–12.5 µg/mL). Together with p-fluoro and p-CF(3) fumardiamides 4b,f, compound 4d showed activity against Mycobacterium marinum and 4b,f against M. tuberculosis. In biofilm eradication assay, most of the bacteria, particularly S. aureus, showed susceptibility to fumardiamides. m-CF(3) and m-chloroaniline fumardiamides 4e and 4c showed significant antiviral activity against reovirus-1, sindbis virus and Punta Toro virus (EC(50) = 3.1–5.5 µM), while 4e was active against coxsackie virus B4 (EC(50) = 3.1 µM). m-Fluoro derivative 4a exerted significant cytostatic activity (IC(50) = 5.7–31.2 μM). Acute lymphoblastic leukemia cells were highly susceptible towards m-substituted derivatives 4a,c,e (IC(50) = 6.7–8.9 μM). Biological evaluations revealed that fumardiamides 4 were more active than succindiamides 5 indicating importance of Michael conjugated system.",2018 Jul 14,"['Rajić, Zrinka', 'Beus, Maja', 'Michnová, Hana', 'Vlainić, Josipa', 'Persoons, Leentje', 'Kosalec, Ivan', 'Jampílek, Josef', 'Schols, Dominique', 'Keser, Toma', 'Zorc, Branka']",Molecules,,,False
36c123eb9cf765e87991924a21da9bdf32e7dc85,PMC,The challenges of treating tracheobronchitis in a laryngectomee due to nontypeable Haemophilus influenzae: a case report,http://dx.doi.org/10.1186/s13256-018-1764-2,PMC6100715,30124173,CC BY,"BACKGROUND: Laryngectomees run the risk of developing severe respiratory tract infections especially during the winter and when they do not wear a stoma cover. A case of severe tracheobronchitis in a laryngectomee is presented that illustrates the risks and difficulties encountered in managing this infection in a neck breather. CASE PRESENTATION: A 76-year-old Caucasian man, a laryngectomee, presented with bacterial tracheobronchitis and conjunctivitis due to beta-lactamase-producing nontypeable Haemophilus influenzae. He was febrile (38.9 °C; 102.0 F), and had repeated episodes of hypertension. He was treated with levofloxacin 500 mg/day, ciprofloxacin eye drops, acetaminophen, and guaifenesin. Humidification of his trachea and the airway was sustained by insertions of saline into the stoma as well as breathing humidified air. The main challenge was to maintain the patency of his airway as the mucus was very dry and viscous and tended to stick to the walls of his trachea and the stoma. His condition improved within 7 days and he had a complete recovery. CONCLUSIONS: Maintaining the patency of the airway in laryngectomees who suffer from lower respiratory tract infection is of utmost importance as the mucus can be very dry and viscous and can stick to the walls of the trachea and the stoma.",2018 Aug 20,"Brook, Itzhak",J Med Case Rep,,,True
111db95189df3fa90756c174fbb5abff1ca1bb01,PMC,A generalized approach to predicting protein-protein interactions between virus and host,http://dx.doi.org/10.1186/s12864-018-4924-2,PMC6101077,30367586,CC BY,"BACKGROUND: Viral infection involves a large number of protein-protein interactions (PPIs) between virus and its host. These interactions range from the initial binding of viral coat proteins to host membrane receptor to the hijacking the host transcription machinery by viral proteins. Therefore, identifying PPIs between virus and its host helps understand the mechanism of viral infections and design antiviral drugs. Many computational methods have been developed to predict PPIs, but most of them are intended for PPIs within a species rather than PPIs across different species such as PPIs between virus and host. RESULTS: In this study, we developed a prediction model of virus-host PPIs, which is applicable to new viruses and hosts. We tested the prediction model on independent datasets of virus-host PPIs, which were not used in training the model. Despite a low sequence similarity between proteins in training datasets and target proteins in test datasets, the prediction model showed a high performance comparable to the best performance of other methods for single virus-host PPIs. CONCLUSIONS: Our method will be particularly useful to find PPIs between host and new viruses for which little information is available. The program and support data are available at http://bclab.inha.ac.kr/VirusHostPPI.",2018 Aug 13,"['Zhou, Xiang', 'Park, Byungkyu', 'Choi, Daesik', 'Han, Kyungsook']",BMC Genomics,,,True
8fc0e17fe32585f3e3216b48c7beba4b15221e57,PMC,Generating genomic platforms to study Candida albicans pathogenesis,http://dx.doi.org/10.1093/nar/gky594,PMC6101633,29982705,CC BY,"The advent of the genomic era has made elucidating gene function on a large scale a pressing challenge. ORFeome collections, whereby almost all ORFs of a given species are cloned and can be subsequently leveraged in multiple functional genomic approaches, represent valuable resources toward this endeavor. Here we provide novel, genome-scale tools for the study of Candida albicans, a commensal yeast that is also responsible for frequent superficial and disseminated infections in humans. We have generated an ORFeome collection composed of 5099 ORFs cloned in a Gateway™ donor vector, representing 83% of the currently annotated coding sequences of C. albicans. Sequencing data of the cloned ORFs are available in the CandidaOrfDB database at http://candidaorfeome.eu. We also engineered 49 expression vectors with a choice of promoters, tags and selection markers and demonstrated their applicability to the study of target ORFs transferred from the C. albicans ORFeome. In addition, the use of the ORFeome in the detection of protein–protein interaction was demonstrated. Mating-compatible strains as well as Gateway™-compatible two-hybrid vectors were engineered, validated and used in a proof of concept experiment. These unique and valuable resources should greatly facilitate future functional studies in C. albicans and the elucidation of mechanisms that underlie its pathogenicity.",2018 Aug 21,"['Legrand, Mélanie', 'Bachellier-Bassi, Sophie', 'Lee, Keunsook K', 'Chaudhari, Yogesh', 'Tournu, Hélène', 'Arbogast, Laurence', 'Boyer, Hélène', 'Chauvel, Murielle', 'Cabral, Vitor', 'Maufrais, Corinne', 'Nesseir, Audrey', 'Maslanka, Irena', 'Permal, Emmanuelle', 'Rossignol, Tristan', 'Walker, Louise A', 'Zeidler, Ute', 'Znaidi, Sadri', 'Schoeters, Floris', 'Majgier, Charlotte', 'Julien, Renaud A', 'Ma, Laurence', 'Tichit, Magali', 'Bouchier, Christiane', 'Van\xa0Dijck, Patrick', 'Munro, Carol A', 'd’Enfert, Christophe']",Nucleic Acids Res,,,True
5a30830e70d1c318a8e5760f24eec2e3ba6ceb5a,PMC,Deficient humoral responses and disrupted B-cell immunity are associated with fatal SFTSV infection,http://dx.doi.org/10.1038/s41467-018-05746-9,PMC6102208,30127439,CC BY,"Severe Fever with Thrombocytopenia Syndrome (SFTS), an emerging infectious disease caused by a novel phlebovirus, is associated with high fatality. Therapeutic interventions are lacking and disease pathogenesis is yet to be fully elucidated. The anti-viral immune response has been reported, but humoral involvement in viral pathogenesis is poorly understood. Here we show defective serological responses to SFTSV is associated with disease fatality and a combination of B-cell and T-cell impairment contribute to disruption of anti-viral immunity. The serological profile in deceased patients is characterized by absence of specific IgG to viral nucleocapsid and glycoprotein due to failure of B-cell class switching. Expansion and impairment of antibody secretion is a signature of fatal SFTSV infection. Apoptosis of monocytes in the early stage of infection diminishes antigen-presentation by dendritic cells, impedes differentiation and function of T follicular helper cells, and contributes to failure of the virus-specific humoral response.",2018 Aug 20,"['Song, Peixin', 'Zheng, Nan', 'Liu, Yong', 'Tian, Chen', 'Wu, Xilin', 'Ma, Xiaohua', 'Chen, Deyan', 'Zou, Xue', 'Wang, Guiyang', 'Wang, Huanru', 'Zhang, Yongyang', 'Lu, Sufang', 'Wu, Chao', 'Wu, Zhiwei']",Nat Commun,,,False
4491bb88635bf0a02fd1e0475f98dcb23d9b5a2b,PMC,Deficient humoral responses and disrupted B-cell immunity are associated with fatal SFTSV infection,http://dx.doi.org/10.1038/s41467-018-05746-9,PMC6102208,30127439,CC BY,"Severe Fever with Thrombocytopenia Syndrome (SFTS), an emerging infectious disease caused by a novel phlebovirus, is associated with high fatality. Therapeutic interventions are lacking and disease pathogenesis is yet to be fully elucidated. The anti-viral immune response has been reported, but humoral involvement in viral pathogenesis is poorly understood. Here we show defective serological responses to SFTSV is associated with disease fatality and a combination of B-cell and T-cell impairment contribute to disruption of anti-viral immunity. The serological profile in deceased patients is characterized by absence of specific IgG to viral nucleocapsid and glycoprotein due to failure of B-cell class switching. Expansion and impairment of antibody secretion is a signature of fatal SFTSV infection. Apoptosis of monocytes in the early stage of infection diminishes antigen-presentation by dendritic cells, impedes differentiation and function of T follicular helper cells, and contributes to failure of the virus-specific humoral response.",2018 Aug 20,"['Song, Peixin', 'Zheng, Nan', 'Liu, Yong', 'Tian, Chen', 'Wu, Xilin', 'Ma, Xiaohua', 'Chen, Deyan', 'Zou, Xue', 'Wang, Guiyang', 'Wang, Huanru', 'Zhang, Yongyang', 'Lu, Sufang', 'Wu, Chao', 'Wu, Zhiwei']",Nat Commun,,,True
440cc2be974b6cafe5ba948e02adbd679e1614a9,PMC,Deficient humoral responses and disrupted B-cell immunity are associated with fatal SFTSV infection,http://dx.doi.org/10.1038/s41467-018-05746-9,PMC6102208,30127439,CC BY,"Severe Fever with Thrombocytopenia Syndrome (SFTS), an emerging infectious disease caused by a novel phlebovirus, is associated with high fatality. Therapeutic interventions are lacking and disease pathogenesis is yet to be fully elucidated. The anti-viral immune response has been reported, but humoral involvement in viral pathogenesis is poorly understood. Here we show defective serological responses to SFTSV is associated with disease fatality and a combination of B-cell and T-cell impairment contribute to disruption of anti-viral immunity. The serological profile in deceased patients is characterized by absence of specific IgG to viral nucleocapsid and glycoprotein due to failure of B-cell class switching. Expansion and impairment of antibody secretion is a signature of fatal SFTSV infection. Apoptosis of monocytes in the early stage of infection diminishes antigen-presentation by dendritic cells, impedes differentiation and function of T follicular helper cells, and contributes to failure of the virus-specific humoral response.",2018 Aug 20,"['Song, Peixin', 'Zheng, Nan', 'Liu, Yong', 'Tian, Chen', 'Wu, Xilin', 'Ma, Xiaohua', 'Chen, Deyan', 'Zou, Xue', 'Wang, Guiyang', 'Wang, Huanru', 'Zhang, Yongyang', 'Lu, Sufang', 'Wu, Chao', 'Wu, Zhiwei']",Nat Commun,,,True
30e8d03a5cf6907154b5a3d7c7b23cdc96cf1952,PMC,Aspergillus PCR in Bronchoalveolar Lavage Fluid for the Diagnosis and Prognosis of Aspergillosis in Patients With Hematological and Non-hematological Conditions,http://dx.doi.org/10.3389/fmicb.2018.01877,PMC6102318,30154779,CC BY,"Objectives: We evaluated the usefulness of an Aspergillus fumigatus quantitative PCR assay performed in bronchoalveolar lavage fluid (BAL) for the diagnosis and prognosis of both invasive and non-invasive aspergillosis. Methods: This 4-year retrospective study involved 613 at-risk patients who had either hematological disorders or other immunosuppressive conditions, notably solid organ transplants. Thirty-five patients had proven/probable aspergillosis and thirteen had chronic non-invasive aspergillosis. We compared PCR, galactomannan index and mycological analysis of BAL. Results: For invasive aspergillosis (IA), PCR performed in BAL yielded 88.6% sensitivity and 95.5% specificity. Comparatively, galactomannan index and mycological examination yielded only 56.3 and 63.6% sensitivity and 97.6 and 94.5% specificity, respectively. Considering the 13 chronic aspergillosis cases, PCR, galactomannan index and mycological examination yielded 76.9, 15.4, and 84.6% sensitivity and 92.2, 94.9, and 93% specificity, respectively. Fungal load in BAL evaluated by PCR was able to discriminate between aspergillosis and contamination, but not between invasive and non-invasive forms. Finally, fungal load was predictive of 90-day mortality, with 23.1% mortality for patients with less than 500 copies/mL versus 68.4% for patients above that cut-off (p < 0.05). Conclusion: Our results indicate that Aspergillus PCR in BAL is of particular interest for both the diagnosis and the prognosis of IA. It is likewise an interesting tool for the diagnosis of non-invasive forms.",2018 Aug 14,"['Imbert, Sébastien', 'Meyer, Isabelle', 'Palous, Martine', 'Brossas, Jean-Yves', 'Uzunov, Madalina', 'Touafek, Feriel', 'Gay, Frédérick', 'Trosini-Desert, Valéry', 'Fekkar, Arnaud']",Front Microbiol,,,True
f012e9f73359ad9dbd89f041c7b5380301e1610b,PMC,How many species of Apodemus and Rattus occur in China? A survey based on mitochondrial cyt b and morphological analyses,http://dx.doi.org/10.24272/j.issn.2095-8137.2018.053,PMC6102683,29955026,CC BY,"Apodemus (mice) and Rattus (rats) are the top rodent reservoirs for zoonoses in China, yet little is known about their diversity. We reexamined the alpha diversity of these two genera based on a new collection of specimens from China and their cyt b sequences in GenBank. We also tested whether species could be identified using external and craniodental measurements exclusively. Measurements from 147 specimens of Apodemus and 233 specimens of Rattus were used for morphological comparisons. We analysed 74 cyt b sequences of Apodemus and 100 cyt b sequences of Rattus to facilitate phylogenetic estimations. Results demonstrated that nine species of Apodemus and seven species of Rattus, plus a new subspecies of Rattus nitidus, are distributed in China. Principal component analysis using external and craniodental measurements revealed that measurements alone could not separate the recognized species. The occurrence of Rattus pyctoris in China remains uncertain.",2018 Sep 18,"['Liu, Shao-Ying', 'He, Kai', 'Chen, Shun-De', 'Jin, Wei', 'Murphy, Robert W.', 'Tang, Ming-Kun', 'Liao, Rui', 'Li, Feng-Jun']",Zool Res,,,True
fb833d8df33cd6cc025d22afa9b7831725ea0afb,PMC,Development and application of an indirect ELISA for the detection of antibodies to porcine epidemic diarrhea virus based on a recombinant spike protein,http://dx.doi.org/10.1186/s12917-018-1570-5,PMC6102851,30126390,CC BY,"BACKGROUND: As the major causative agent of swine viral diarrhea, porcine epidemic diarrhea virus (PEDV) has caused massive losses to the economies of swine raising countries. Accordingly, the serological detection of corresponding antibodies would be beneficial to diagnose PEDV indirectly to control the disease. In this study, an indirect enzyme-linked immunosorbent assay (ELISA) based on the recombinant truncated spike (S) protein of PEDV was developed and validated. RESULTS: The reaction conditions of the developed indirect ELISA were optimized. This indirect ELISA was compared to indirect immunoinfluscent assay (IFA), and the overall coincidence rate was 96.74% based on testing 368 clinical serum samples with different PEDV antibody levels. No cross-reactivity with other common swine pathogens was detected for the developed S1 indirect ELISA. Finally, the S1 indirect ELISA was applied to detect serum antibodies of 3304 field samples collected from different pig farms in eastern China, and it presented an overall substantial agreement on the PEDV infection status. CONCLUSIONS: This established S1 indirect ELISA is capable of detecting serum antibodies against PEDV, and due to its high sensitivity and specificity, it could be applied for serological evaluation and indirect diagnosis of PEDV infection.",2018 Aug 20,"['Lin, Huixing', 'Zhou, Hong', 'Gao, Lu', 'Li, Bin', 'He, Kongwang', 'Fan, Hongjie']",BMC Vet Res,,,True
15c791fd40a5b37bcec8cefb0a3300ad6a50bd77,PMC,"Experiences and challenges in the health protection of medical teams in the Chinese Ebola treatment center, Liberia: a qualitative study",http://dx.doi.org/10.1186/s40249-018-0468-6,PMC6103862,30134982,CC BY,"BACKGROUND: Health care workers are at the frontline in the fight against infectious disease, and as a result are at a high risk of infection. During the 2014–2015 Ebola outbreak in West Africa, many health care workers contracted Ebola, some fatally. However, no members of the Chinese Anti-Ebola medical team, deployed to provide vital medical care in Liberia were infected. This study aims to understand how this zero infection rate was achieved. METHODS: Data was collected through 15 in-depth interviews with participants from the People’s Liberation Army of China medical team which operated the Chinese Ebola Treatment Center from October 2014 to January 2015 in Liberia. Data were analysed using systematic framework analysis. RESULTS: This study found numerous bio-psycho-socio-behavioural risk factors that directly or indirectly threatened the health of the medical team working in the Chinese Ebola Treatment Center. These factors included social and emotional stress caused by: (1) the disruption of family and social networks; (2) adapting to a different culture; (3) and anxiety over social and political unrest in Liberia. Exposure to Ebola from patients and local co-workers, and the incorrect use of personal protective equipment due to fatigue was another major risk factor. Other risk factors identified were: (1) shortage of supplies; (2) lack of trained health personnel; (3) exposure to contaminated food and water; (4) and long working hours. Comprehensive efforts were taken throughout the mission to mitigate these factors. Every measure was taken to prevent the medical team’s exposure to the Ebola virus, and to provide the medical team with safe, comfortable working and living environments. There were many challenges in maintaining the health safety of the team, such as the limited capability of the emergency command system (the standardized approach to the command, control, and coordination of an emergency response), and the lack of comprehensive international protocols for dealing with emerging infectious disease pandemics. CONCLUSIONS: The comprehensive and multidisciplinary measures employed to protect the health of the medical team proved successful even in Liberia’s resource-limited setting. The global health community can learn valuable lessons from this experience which could improve the safety of health care workers in future emergencies. These lessons include: establishing capable command systems; implementing effective coordination mechanisms; providing adequate equipment; providing training for medical teams; investing in the development of global health professionals; and improving research on ways to protect health care workers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-018-0468-6) contains supplementary material, which is available to authorized users.",2018 Aug 16,"['Li, Ying', 'Wang, Huan', 'Jin, Xu-Rui', 'Li, Xiang', 'Pender, Michelle', 'Song, Cai-Ping', 'Tang, Sheng-Lan', 'Cao, Jia', 'Wu, Hao', 'Wang, Yun-Gui']",Infect Dis Poverty,,,False
5f6cbbe720247466895b4469f21b0967b35feb5a,PMC,"Experiences and challenges in the health protection of medical teams in the Chinese Ebola treatment center, Liberia: a qualitative study",http://dx.doi.org/10.1186/s40249-018-0468-6,PMC6103862,30134982,CC BY,"BACKGROUND: Health care workers are at the frontline in the fight against infectious disease, and as a result are at a high risk of infection. During the 2014–2015 Ebola outbreak in West Africa, many health care workers contracted Ebola, some fatally. However, no members of the Chinese Anti-Ebola medical team, deployed to provide vital medical care in Liberia were infected. This study aims to understand how this zero infection rate was achieved. METHODS: Data was collected through 15 in-depth interviews with participants from the People’s Liberation Army of China medical team which operated the Chinese Ebola Treatment Center from October 2014 to January 2015 in Liberia. Data were analysed using systematic framework analysis. RESULTS: This study found numerous bio-psycho-socio-behavioural risk factors that directly or indirectly threatened the health of the medical team working in the Chinese Ebola Treatment Center. These factors included social and emotional stress caused by: (1) the disruption of family and social networks; (2) adapting to a different culture; (3) and anxiety over social and political unrest in Liberia. Exposure to Ebola from patients and local co-workers, and the incorrect use of personal protective equipment due to fatigue was another major risk factor. Other risk factors identified were: (1) shortage of supplies; (2) lack of trained health personnel; (3) exposure to contaminated food and water; (4) and long working hours. Comprehensive efforts were taken throughout the mission to mitigate these factors. Every measure was taken to prevent the medical team’s exposure to the Ebola virus, and to provide the medical team with safe, comfortable working and living environments. There were many challenges in maintaining the health safety of the team, such as the limited capability of the emergency command system (the standardized approach to the command, control, and coordination of an emergency response), and the lack of comprehensive international protocols for dealing with emerging infectious disease pandemics. CONCLUSIONS: The comprehensive and multidisciplinary measures employed to protect the health of the medical team proved successful even in Liberia’s resource-limited setting. The global health community can learn valuable lessons from this experience which could improve the safety of health care workers in future emergencies. These lessons include: establishing capable command systems; implementing effective coordination mechanisms; providing adequate equipment; providing training for medical teams; investing in the development of global health professionals; and improving research on ways to protect health care workers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-018-0468-6) contains supplementary material, which is available to authorized users.",2018 Aug 16,"['Li, Ying', 'Wang, Huan', 'Jin, Xu-Rui', 'Li, Xiang', 'Pender, Michelle', 'Song, Cai-Ping', 'Tang, Sheng-Lan', 'Cao, Jia', 'Wu, Hao', 'Wang, Yun-Gui']",Infect Dis Poverty,,,True
41109a7485f8648bc39545c38aa0dea1e8460f17,PMC,Coxsackievirus A6 Induces Cell Cycle Arrest in G0/G1 Phase for Viral Production,http://dx.doi.org/10.3389/fcimb.2018.00279,PMC6104138,30159255,CC BY,"Recent epidemiological data indicate that outbreaks of hand, foot, and mouth disease (HFMD), which can be categorized according to its clinical symptoms as typical or atypical, have markedly increased worldwide. A primary causative agent for typical HFMD outbreaks, enterovirus 71 (EV71), has been shown to manipulate the cell cycle in S phase for own replication; however, it is not clear whether coxsackievirus (CVA6), the main agent for atypical HFMD, also regulates the host cell cycle. In this study, we demonstrate for the first time that CVA6 infection arrests the host cell cycle in G0/G1-phase. Furthermore, synchronization in G0/G1 phase, but not S phase or G2/M phase, promotes viral production. To investigate the mechanism of cell cycle arrest induced by CVA6 infection, we analyzed cell cycle progression after cell cycle synchronization at G0/G1 or G2/M. Our results demonstrate that CVA6 infection promotes G0/G1 phase entry from G2/M phase, and inhibits G0/G1 exit into S phase. In line with its role to arrest cells in G0/G1 phase, the expression of cyclinD1, CDK4, cyclinE1, CDK2, cyclinB1, CDK1, P53, P21, and P16 is regulated by CVA6. Finally, the non-structural proteins of CVA6, RNA-dependent RNA polymerase 3D and protease 3C , are demonstrated to be responsible for the G0/G1-phase arrest. These findings suggest that CVA6 infection arrested cell cycle in G0/G1-phase via non-structural proteins 3D and 3C, which may provide favorable environments for virus production.",2018 Aug 15,"['Wang, Zengyan', 'Wang, Yue', 'Wang, Shaohua', 'Meng, Xiangling', 'Song, Fengmei', 'Huo, Wenbo', 'Zhang, Shuxia', 'Chang, Junliang', 'Li, Jingliang', 'Zheng, Baisong', 'Liu, Yanqiu', 'Zhang, Yahong', 'Zhang, Wenyan', 'Yu, Jinghua']",Front Cell Infect Microbiol,,,True
05e506d7af33ce5dee01e954250d2a83796ba596,PMC,Isolation and characterization of novel bat paramyxovirus B16-40 potentially belonging to the proposed genus Shaanvirus,http://dx.doi.org/10.1038/s41598-018-30319-7,PMC6105681,30135435,CC BY,"The bat paramyxovirus B16-40 was first isolated in Korea in this study. Using the isolated virus, we could obtain not only genomic information, but also several biological characteristics of the virus. In the phylogenetic analysis, the virus was found to belong to the recently proposed genus Shaanvirus. Through sequence analyses and in vitro testing, the isolated virus was also found to have haemagglutinin-neuraminidase (HN) protein as one of the structural proteins. When mouse antiserum was generated against the isolated virus and tested, it was cross-reactive to human parainfluenza virus 1 in an indirect immunofluorescence assay but could not cross-neutralize human parainfluenza virus 1. In addition, the bat paramyxovirus B16-40 was not infectious in the mouse model. Collectively, this study provided basic information on further classification of the bat paramyxovirus B16-40 and related viruses in the proposed genus Shaanvirus.",2018 Aug 22,"['Noh, Ji Yeong', 'Jeong, Dae Gwin', 'Yoon, Sun-Woo', 'Kim, Ji Hyung', 'Choi, Yong Gun', 'Kang, Shien-Young', 'Kim, Hye Kwon']",Sci Rep,,,False
36c57bd8ded4b2dc1a5859c15dea5c3800e23413,PMC,Isolation and characterization of novel bat paramyxovirus B16-40 potentially belonging to the proposed genus Shaanvirus,http://dx.doi.org/10.1038/s41598-018-30319-7,PMC6105681,30135435,CC BY,"The bat paramyxovirus B16-40 was first isolated in Korea in this study. Using the isolated virus, we could obtain not only genomic information, but also several biological characteristics of the virus. In the phylogenetic analysis, the virus was found to belong to the recently proposed genus Shaanvirus. Through sequence analyses and in vitro testing, the isolated virus was also found to have haemagglutinin-neuraminidase (HN) protein as one of the structural proteins. When mouse antiserum was generated against the isolated virus and tested, it was cross-reactive to human parainfluenza virus 1 in an indirect immunofluorescence assay but could not cross-neutralize human parainfluenza virus 1. In addition, the bat paramyxovirus B16-40 was not infectious in the mouse model. Collectively, this study provided basic information on further classification of the bat paramyxovirus B16-40 and related viruses in the proposed genus Shaanvirus.",2018 Aug 22,"['Noh, Ji Yeong', 'Jeong, Dae Gwin', 'Yoon, Sun-Woo', 'Kim, Ji Hyung', 'Choi, Yong Gun', 'Kang, Shien-Young', 'Kim, Hye Kwon']",Sci Rep,,,True
d5d68ccc9849f408aadaeb9c522469d610f323b6,PMC,Cordyceps industry in China,http://dx.doi.org/10.1080/21501203.2015.1043967,PMC6106062,30151320,CC BY,"Cordyceps, as a general term, describes a group of ascomycetous fungi growing on arthropods and other related fungi. Some cordyceps have been used in traditional Chinese medicine for centuries and cordyceps-derived products are currently a big industry in China. A number of medicinal and health products have been developed and extensively commercialized from natural Chinese cordyceps, its anamorphic fungus (Hirsutella sinensis), and other fungi known as Chinese cordyceps. The lack of a defined classification system for medicinal cordyceps fungi is a source of confusion in the industry and the public, and even among pharmaceutical scientists. This review summarizes the cordyceps fungi currently used in the industry in China with a special reference to clarify Chinese cordyceps and associated fungi. Cordyceps militaris, Cordyceps guangdongensis and Isaria cicadae are well recognized and commercialized cordyceps fungi in China. Except the natural Chinese cordyceps and its anamorphic fungus, Paecilomyces hepiali, Mortierella hepiali, Cephalosporium sinensis and Clonostachys rosea isolated from natural Chinese cordyceps are classified as Chinese cordyceps–associated fungi. P. hepiali is a cordyceps fungus based on current phylogenetic analysis of Hypocreales, while M. hepiali is a fungus in the Zygomycetes and should only be treated as associated fungus of Chinese cordyceps. C. sinensis and C. rosea belong to the Hypocreales and their relationship to cordyceps fungi should be further studied. The exploitation of the resources of cordyceps fungi and their quality control in the industry should be major topics for future studies. Cooperation between the industry and the research community will enhance the whole cordyceps industry.",2015 May 21,"['Dong, Caihong', 'Guo, Suping', 'Wang, Wenfeng', 'Liu, Xingzhong']",Mycology,,,True
f328ee900e91ba6c3bcc9a8f27e8fac7cd8c5eeb,PMC,Serological and Molecular Surveillance of Infectious Bronchitis Virus Infection in Free-Range Chickens and Guinea Fowls in the Ga-East District of Ghana,http://dx.doi.org/10.1155/2018/4949580,PMC6106965,30159336,CC BY,"Infectious bronchitis is an economically important disease with worldwide distribution. Information is available on the presence of infectious bronchitis virus in commercial chicken in parts of Ghana but there is no information on free-range poultry and guinea fowls in the country. Possible IBV infections among free-range chickens and guinea fowls in Abokobi and Frafraha communities in the Ga-East district of the Greater Accra Region of Ghana were investigated using serology and PCR. Blood, tracheal, and cloacal swabs were obtained from 219 free-range chickens and guinea fowls with no respiratory symptoms and no history of IBV vaccination. Sera were evaluated for IBV antibodies by ELISA using commercial IBV test kit from IDEXX, Inc., USA. Swab samples were evaluated for S1 glycoprotein gene by one-step RT PCR. All the swab samples tested negative for IBV. 16% of all tested sera were positive for IBV. IBV seroprevalence in guinea fowls was 0%. 21.2% of sera from local chickens were positive for IBV. The seroprevalence of IBV among local chickens from Frafraha was 30% and that of Abokobi was 7.7%. This study shows exposure of local chickens in the study communities to IBV.",2018 Aug 6,"['Ayim-Akonor, Matilda', 'Owusu-Ntumy, Doreen Dela', 'Ohene-Asa, Hilda Emefa', 'Oduro-Abrokwa, Agyekum', 'Hammond, Patricia', 'Appenteng, Michael', 'Annan, Daniel']",J Vet Med,,,True
1c7c9d9c03f404119c5cc1dd98e0ebe17ea3bb3e,PMC,Interferon-beta expression and type I interferon receptor signaling of hepatocytes prevent hepatic necrosis and virus dissemination in Coxsackievirus B3-infected mice,http://dx.doi.org/10.1371/journal.ppat.1007235,PMC6107283,30075026,CC BY,"During Coxsackievirus B3 (CVB3) infection hepatitis is a potentially life threatening complication, particularly in newborns. Studies with type I interferon (IFN-I) receptor (IFNAR)-deficient mice revealed a key role of the IFN-I axis in the protection against CVB3 infection, whereas the source of IFN-I and cell types that have to be IFNAR triggered in order to promote survival are still unknown. We found that CVB3 infected IFN-β reporter mice showed effective reporter induction, especially in hepatocytes and only to a minor extent in liver-resident macrophages. Accordingly, upon in vitro CVB3 infection of primary hepatocytes from murine or human origin abundant IFN-β responses were induced. To identify sites of IFNAR-triggering we performed experiments with Mx reporter mice, which upon CVB3 infection showed massive luciferase induction in the liver. Immunohistological studies revealed that during CVB3 infection MX1 expression of hepatocytes was induced primarily by IFNAR-, and not by IFN-III receptor (IFNLR)-triggering. CVB3 infection studies with primary human hepatocytes, in which either the IFN-I or the IFN-III axis was inhibited, also indicated that primarily IFNAR-, and to a lesser extent IFNLR-triggering was needed for ISG induction. Interestingly, CVB3 infected mice with a hepatocyte-specific IFNAR ablation showed severe liver cell necrosis and ubiquitous viral dissemination that resulted in lethal disease, as similarly detected in classical IFNAR(-/-) mice. In conclusion, we found that during CVB3 infection hepatocytes are major IFN-I producers and that the liver is also the organ that shows strong IFNAR-triggering. Importantly, hepatocytes need to be IFNAR-triggered in order to prevent virus dissemination and to assure survival. These data are compatible with the hypothesis that during CVB3 infection hepatocytes serve as important IFN-I producers and sensors not only in the murine, but also in the human system.",2018 Aug 3,"['Koestner, Wolfgang', 'Spanier, Julia', 'Klause, Tanja', 'Tegtmeyer, Pia-K.', 'Becker, Jennifer', 'Herder, Vanessa', 'Borst, Katharina', 'Todt, Daniel', 'Lienenklaus, Stefan', 'Gerhauser, Ingo', 'Detje, Claudia N.', 'Geffers, Robert', 'Langereis, Martijn A.', 'Vondran, Florian W. R.', 'Yuan, Qinggong', 'van Kuppeveld, Frank J. M.', 'Ott, Michael', 'Staeheli, Peter', 'Steinmann, Eike', 'Baumgärtner, Wolfgang', 'Wacker, Frank', 'Kalinke, Ulrich']",PLoS Pathog,,,True
e0f1b5a380193e6ff0a4de4d44d74ad309a5dda3,PMC,Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2,http://dx.doi.org/10.1371/journal.ppat.1007236,PMC6107290,30102747,CC BY,"The trimeric SARS coronavirus (SARS-CoV) surface spike (S) glycoprotein consisting of three S1-S2 heterodimers binds the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediates fusion of the viral and cellular membranes through a pre- to postfusion conformation transition. Here, we report the structure of the SARS-CoV S glycoprotein in complex with its host cell receptor ACE2 revealed by cryo-electron microscopy (cryo-EM). The complex structure shows that only one receptor-binding domain of the trimeric S glycoprotein binds ACE2 and adopts a protruding “up” conformation. In addition, we studied the structures of the SARS-CoV S glycoprotein and its complexes with ACE2 in different in vitro conditions, which may mimic different conformational states of the S glycoprotein during virus entry. Disassociation of the S1-ACE2 complex from some of the prefusion spikes was observed and characterized. We also characterized the rosette-like structures of the clustered SARS-CoV S2 trimers in the postfusion state observed on electron micrographs. Structural comparisons suggested that the SARS-CoV S glycoprotein retains a prefusion architecture after trypsin cleavage into the S1 and S2 subunits and acidic pH treatment. However, binding to the receptor opens up the receptor-binding domain of S1, which could promote the release of the S1-ACE2 complex and S1 monomers from the prefusion spike and trigger the pre- to postfusion conformational transition.",2018 Aug 13,"['Song, Wenfei', 'Gui, Miao', 'Wang, Xinquan', 'Xiang, Ye']",PLoS Pathog,,,True
8a696028212fb6b878bf7143927566fdb6215f06,PMC,Kinetic analysis of the influenza A virus HA/NA balance reveals contribution of NA to virus-receptor binding and NA-dependent rolling on receptor-containing surfaces,http://dx.doi.org/10.1371/journal.ppat.1007233,PMC6107293,30102740,CC BY,"Interactions of influenza A virus (IAV) with sialic acid (SIA) receptors determine viral fitness and host tropism. Binding to mucus decoy receptors and receptors on epithelial host cells is determined by a receptor-binding hemagglutinin (HA), a receptor-destroying neuraminidase (NA) and a complex in vivo receptor-repertoire. The crucial but poorly understood dynamics of these multivalent virus-receptor interactions cannot be properly analyzed using equilibrium binding models and endpoint binding assays. In this study, the use of biolayer interferometric analysis revealed the virtually irreversible nature of IAV binding to surfaces coated with synthetic sialosides or engineered sialoglycoproteins in the absence of NA activity. In addition to HA, NA was shown to be able to contribute to the initial binding rate while catalytically active. Virus-receptor binding in turn contributed to receptor cleavage by NA. Multiple low-affinity HA-SIA interactions resulted in overall extremely high avidity but also permitted a dynamic binding mode, in which NA activity was driving rolling of virus particles over the receptor-surface. Virus dissociation only took place after receptor density of the complete receptor-surface was sufficiently decreased due to NA activity of rolling IAV particles. The results indicate that in vivo IAV particles, after landing on the mucus layer, reside continuously in a receptor-bound state while rolling through the mucus layer and over epithelial cell surfaces driven by the HA-NA-receptor balance. Quantitative BLI analysis enabled functional examination of this balance which governs this dynamic and motile interaction that is expected to be crucial for penetration of the mucus layer and subsequent infection of cells by IAV but likely also by other enveloped viruses carrying a receptor-destroying enzyme in addition to a receptor-binding protein.",2018 Aug 13,"['Guo, Hongbo', 'Rabouw, Huib', 'Slomp, Anne', 'Dai, Meiling', 'van der Vegt, Floor', 'van Lent, Jan W. M.', 'McBride, Ryan', 'Paulson, James C.', 'de Groot, Raoul J.', 'van Kuppeveld, Frank J. M.', 'de Vries, Erik', 'de Haan, Cornelis A. M.']",PLoS Pathog,,,True
29e5350bd66573e9e7d304b12b1f551fe59e05f2,PMC,Old Master Zhu: in memory of virologist Guan-Fu Zhu,http://dx.doi.org/10.1007/s13238-017-0396-4,PMC6107489,28316032,CC BY,,2018 Sep 18,"['Ye, Qing', 'Jiang, Tao', 'Qin, Cheng-Feng']",Protein Cell,,,True
0f4b565dd039cbdf2573b6f674e9a502d9230703,PMC,Multiplex Detection of Five Canine Viral Pathogens for Dogs as Laboratory Animals by the Luminex xTAG Assay,http://dx.doi.org/10.3389/fmicb.2018.01783,PMC6107692,30174654,CC BY,"More and more dogs have been used as a disease model for medical research and drug safety evaluation. Therefore, it is important to make sure that the dogs and their living houses are special pathogen free. In this study, the development and evaluation of a Luminex xTAG assay for simultaneous detection of five canine viruses was carried out, including canine distemper virus, canine parvovirus, canine parainfluenza virus, canine adenovirus, and rabies virus. Assay specificity was accomplished by targeting conserved genomic regions for each virus. Hybridization between multiplexed PCR products and the labeled fluorescence microspheres was detected in a high throughput format using a Luminex fluorescence reader. The Luminex xTAG assay showed high sensitivity with limits of detection for the five viruses was 100 copies/μL. Specificity of the xTAG assay showed no amplification of canine coronavirus, pseudorabies virus and canine influenza virus indicating that the xTAG assay was specific. Seventy-five clinical samples were tested to evaluate the xTAG assay. The results showed 100% coincidence with the conventional PCR method. This is the first report of a specific and sensitive multiplex Luminex xTAG assay for simultaneous detection of five major canine viral pathogens. This assay will be a useful tool for quality control and environmental monitoring for dogs used as laboratory animals, may even be applied in laboratory epidemiological investigations.",2018 Aug 17,"['Wu, Miaoli', 'Cong, Feng', 'Zhu, Yujun', 'Lian, Yuexiao', 'Chen, Meili', 'Huang, Ren', 'Guo, Pengju']",Front Microbiol,,,True
7d80b4b324ef2dd14af229db302d015995befee8,PMC,Prevalence of Respiratory Polyomaviruses Among Pediatric Patients With Respiratory Symptoms in Singapore,http://dx.doi.org/10.3389/fped.2018.00228,PMC6107759,30175090,CC BY,"Background: Although WU polyomavirus (WU) and KI polyomavirus (KI) have been demonstrated to infect the human respiratory tract, it remains unclear if WU or KI cause human disease. We sought to further investigate the relationship between WU and KI infection and respiratory disease in a pediatric population with respiratory symptoms in Singapore. Methods: We conducted a cross-sectional study of pediatric patients with respiratory symptoms in a Singaporean pediatrics hospital. Upon consent, residual respiratory samples from pediatric inpatients, previously screened for common respiratory viruses, were collected and further screened for WU and KI using qPCR. The amplicons of positive samples were sequenced for confirmation. The severity of a patient's illness was assessed by chart review post-discharge looking for clinical markers of respiratory status such as presenting symptoms, diagnoses, and interventions. Results: From December 2016 to April 2017, 201 patients with residual respiratory samples were enrolled in the study. The average age of all participants recruited was 45 months. WU and KI were detected in 13% (26/201) and 3% (6/201) of patients, respectively. Conducting bivariate and multivariate modeling, patients with WU or KI positivity were not at increased risk of SARI, need for additional oxygen, intravenous fluids, and did not receive additional oral antibiotics or bronchodilators during admission. In contrast, patients with RSV detections were at increased risk of requiring supplemental oxygen during hospital admission. Conclusion: While limited in sample size, our pilot study data do not support the hypothesis that molecular evidence of WU or KI was associated with increased morbidity among a sample of general, pediatric patients with respiratory illness in Singapore.",2018 Aug 17,"['Hansen-Estruch, Christophe', 'Coleman, Kristen K.', 'Thoon, Koh C.', 'Low, Jenny G.', 'Anderson, Benjamin D.', 'Gray, Gregory C.']",Front Pediatr,,,True
23a6cc5f5c3babf3e187374eca3be2a5e052669b,PMC,"Animal infection studies of two recently discovered African bat paramyxoviruses, Achimota 1 and Achimota 2",http://dx.doi.org/10.1038/s41598-018-31193-z,PMC6109078,30143747,CC BY,"Bats are implicated as the natural reservoirs for several highly pathogenic viruses that can infect other animal species, including man. Here, we investigate the potential for two recently discovered bat rubulaviruses, Achimota virus 1 (AchPV1) and Achimota virus 2 (AchPV2), isolated from urine collected under urban bat (Eidolon helvum) roosts in Ghana, West Africa, to infect small laboratory animals. AchPV1 and AchPV2 are classified in the family Paramyxoviridae and cluster with other bat derived zoonotic rubulaviruses (i.e. Sosuga, Menangle and Tioman viruses). To assess the susceptibility of AchPV1 and AchPV2 in animals, infection studies were conducted in ferrets, guinea pigs and mice. Seroconversion, immunohistological evidence of infection, and viral shedding were identified in ferrets and guinea pigs, but not in mice. Infection was associated with respiratory disease in ferrets. Viral genome was detected in a range of tissues from ferrets and guinea pigs, however virus isolation was only achieved from ferret tissues. The results from this study indicate Achimota viruses (AchPVs) are able to cross the species barrier. Consequently, vigilance for infection with and disease caused by these viruses in people and domesticated animals is warranted in sub-Saharan Africa and the Arabian Peninsula where the reservoir hosts are present.",2018 Aug 24,"['Barr, Jennifer', 'Todd, Shawn', 'Crameri, Gary', 'Foord, Adam', 'Marsh, Glenn', 'Frazer, Leah', 'Payne, Jean', 'Harper, Jenni', 'Baker, Kate S.', 'Cunningham, Andrew A.', 'Wood, James L. N.', 'Middleton, Deborah', 'Wang, Lin-Fa']",Sci Rep,,,True
ddddc52ff6183d8092a992286fd64acb18cdf2bd,PMC,The Study of Viral RNA Diversity in Bird Samples Using De Novo Designed Multiplex Genus-Specific Primer Panels,http://dx.doi.org/10.1155/2018/3248285,PMC6109506,30158979,CC BY,"Advances in the next generation sequencing (NGS) technologies have significantly increased our ability to detect new viral pathogens and systematically determine the spectrum of viruses prevalent in various biological samples. In addition, this approach has also helped in establishing the associations of viromes with many diseases. However, unlike the metagenomic studies using 16S rRNA for the detection of bacteria, it is impossible to create universal oligonucleotides to target all known and novel viruses, owing to their genomic diversity and variability. On the other hand, sequencing the entire genome is still expensive and has relatively low sensitivity for such applications. The existing approaches for the design of oligonucleotides for targeted enrichment are usually involved in the development of primers for the PCR-based detection of particular viral species or genera, but not for families or higher taxonomic orders. In this study, we have developed a computational pipeline for designing the oligonucleotides capable of covering a significant number of known viruses within various taxonomic orders, as well as their novel variants. We have subsequently designed a genus-specific oligonucleotide panel for targeted enrichment of viral nucleic acids in biological material and demonstrated the possibility of its application for virus detection in bird samples. We have tested our panel using a number of collected samples and have observed superior efficiency in the detection and identification of viral pathogens. Since a reliable, bioinformatics-based analytical method for the rapid identification of the sequences was crucial, an NGS-based data analysis module was developed in this study, and its functionality in the detection of novel viruses and analysis of virome diversity was demonstrated.",2018 Aug 12,"['Ayginin, Andrey A.', 'Pimkina, Ekaterina V.', 'Matsvay, Alina D.', 'Speranskaya, Anna S.', 'Safonova, Marina V.', 'Blinova, Ekaterina A.', 'Artyushin, Ilya V.', 'Dedkov, Vladimir G.', 'Shipulin, German A.', 'Khafizov, Kamil']",Adv Virol,,,True
4836e3bd00d59bf1af3b4f5000cf917c71655658,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,True
903010cb5e44956d4dcbbf482d27df2967d43eb6,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
b7a181730b683b50daf95208d9d7e2ad855b1663,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
9a57136025597ad9fce227963806c6f7eb060a5a,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
15b48e38dfc63999180e61ca5e8e8e7a6a144e20,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
d50130eae0725f5f09a502af38a11f73064dd75e,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
045a46ba847ef55dc47efe6862aae106f5091bac,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
bd0d4ea2ad0ad9aba00219c247f3b7171c88096a,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
c059539fba1d3c4ac5dea7953c84eea0a95f4324,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
84699282a8fc32f199236807e49ac9492be92771,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
4e36926bc2e73e1aaf3163bab0d0610c4d14f721,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
4288345f492d3104b69e26e6aa3a99cdae698115,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
d6776752526e81705160ff63b1563005011a2381,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
ff15158f190f330aaae175b1dda34fea9377abf5,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
b65829c488a000e9633241e2c40bcb7998f264d1,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
fa94260dc296b86c3eb084e02ce422c926157f25,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
540cf4431ad769af041f219708bcf4f6a41aa1d0,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
b4f71a187f2852c63a42a718e22f2639b0020233,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
0302cd899c3522df1f0892ea1a1fdd9d878d6279,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
fe3f7f7c0394ef99561026faccf0f295a288a57e,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
cda93f801384df590343a55a0c01a418a67684f4,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
17bc516bdc0c646dd811646ff10b4d945ddd0b4f,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
e42b00e80bf026df842bd77cdc9e673c986aa413,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
5697a4288df95d8e50364a2d1d7ce03b04ca3108,PMC,Accounting for non-stationarity in epidemiology by embedding time-varying parameters in stochastic models,http://dx.doi.org/10.1371/journal.pcbi.1006211,PMC6110518,30110322,CC BY,"The spread of disease through human populations is complex. The characteristics of disease propagation evolve with time, as a result of a multitude of environmental and anthropic factors, this non-stationarity is a key factor in this huge complexity. In the absence of appropriate external data sources, to correctly describe the disease propagation, we explore a flexible approach, based on stochastic models for the disease dynamics, and on diffusion processes for the parameter dynamics. Using such a diffusion process has the advantage of not requiring a specific mathematical function for the parameter dynamics. Coupled with particle MCMC, this approach allows us to reconstruct the time evolution of some key parameters (average transmission rate for instance). Thus, by capturing the time-varying nature of the different mechanisms involved in disease propagation, the epidemic can be described. Firstly we demonstrate the efficiency of this methodology on a toy model, where the parameters and the observation process are known. Applied then to real datasets, our methodology is able, based solely on simple stochastic models, to reconstruct complex epidemics, such as flu or dengue, over long time periods. Hence we demonstrate that time-varying parameters can improve the accuracy of model performances, and we suggest that our methodology can be used as a first step towards a better understanding of a complex epidemic, in situation where data is limited and/or uncertain.",2018 Aug 15,"['Cazelles, Bernard', 'Champagne, Clara', 'Dureau, Joseph']",PLoS Comput Biol,,,False
a20dad1dae885e38b8aeadb93c22d14a54c6388a,PMC,Estimating the Asymptomatic Ratio of Norovirus Infection During Foodborne Outbreaks With Laboratory Testing in Japan,http://dx.doi.org/10.2188/jea.JE20170040,PMC6111106,29607886,CC BY,"BACKGROUND: Foodborne norovirus outbreak data in Japan from 2005–2006, involving virological surveillance of all symptomatic and asymptomatic individuals, were reanalyzed to estimate the asymptomatic ratio of norovirus infection along with the risk of infection and the probability of virus shedding. METHODS: Employing a statistical model that is considered to capture the data-generating process of the outbreak and virus surveillance, maximum likelihood estimation of the asymptomatic ratio was implemented. RESULTS: Assuming that all norovirus outbreaks (n = 55) were the result of random sampling from an identical distribution and ignoring genogroup and genotype specificities, the asymptomatic ratio was estimated at 32.1% (95% confidence interval [CI], 27.7–36.7). Although not significant, separate estimation of the asymptomatic ratio of the GII.4 genotype appeared to be greater than other genotypes and was estimated at 40.7% (95% CI, 32.8–49.0). CONCLUSION: The present study offered the first explicit empirical estimates of the asymptomatic ratio of norovirus infection in natural infection settings. The estimate of about 30% was consistent with those derived from volunteer challenge studies. Practical difficulty in controlling GII.4 outbreaks was supported by the data, considering that a large estimate of the asymptomatic ratio was obtained for the GII.4 genotype.",2018 Sep 5,"['Miura, Fuminari', 'Matsuyama, Ryota', 'Nishiura, Hiroshi']",J Epidemiol,,,True
b7d5bd207eb75e868cd7b04bfe3cbbcb88362362,PMC,Estimating the Asymptomatic Ratio of Norovirus Infection During Foodborne Outbreaks With Laboratory Testing in Japan,http://dx.doi.org/10.2188/jea.JE20170040,PMC6111106,29607886,CC BY,"BACKGROUND: Foodborne norovirus outbreak data in Japan from 2005–2006, involving virological surveillance of all symptomatic and asymptomatic individuals, were reanalyzed to estimate the asymptomatic ratio of norovirus infection along with the risk of infection and the probability of virus shedding. METHODS: Employing a statistical model that is considered to capture the data-generating process of the outbreak and virus surveillance, maximum likelihood estimation of the asymptomatic ratio was implemented. RESULTS: Assuming that all norovirus outbreaks (n = 55) were the result of random sampling from an identical distribution and ignoring genogroup and genotype specificities, the asymptomatic ratio was estimated at 32.1% (95% confidence interval [CI], 27.7–36.7). Although not significant, separate estimation of the asymptomatic ratio of the GII.4 genotype appeared to be greater than other genotypes and was estimated at 40.7% (95% CI, 32.8–49.0). CONCLUSION: The present study offered the first explicit empirical estimates of the asymptomatic ratio of norovirus infection in natural infection settings. The estimate of about 30% was consistent with those derived from volunteer challenge studies. Practical difficulty in controlling GII.4 outbreaks was supported by the data, considering that a large estimate of the asymptomatic ratio was obtained for the GII.4 genotype.",2018 Sep 5,"['Miura, Fuminari', 'Matsuyama, Ryota', 'Nishiura, Hiroshi']",J Epidemiol,,,False
f01ad3545245b4f884b48aa2b69c9deb942c3e77,PMC,Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients,http://dx.doi.org/10.1155/2018/2514901,PMC6112080,30186532,CC BY,"Hepatitis C Virus (HCV) infection treatment has dramatically changed with the advent of direct-acting antiviral agents (DAAs). However, the efficacy of DAAs can be attenuated by the presence of resistance-associated substitutions (RASs) before and after treatment. Indeed, RASs detected in DAA treatment-naïve HCV-infected patients could be useful for clinical management and outcome prediction. Although the frequency of naturally occurring HCV NS5A and NS5B RASs has been addressed in many countries, there are only a few reports on their prevalence in the South American region. The aim of this study was to investigate the presence of RASs to NS5A and NS5B inhibitors in a DAA treatment naïve cohort of Uruguayan patients infected with chronic hepatitis C and compare them with reports from other South American countries. Here, we found that naturally occurring substitutions conferring resistance to NS5A and NS5B inhibitors were present in 8% and 19.2%, respectively, of treatment-naïve HCV genotype 1 infected patients. Importantly, the baseline substitutions in NS5A and NS5B herein identified differ from the studies previously reported in Brazil. Furthermore, Uruguayan strains subtype 1a clustered within all major world clades, showing that HCV variants currently circulating in this country are characterized by a remarkable genetic diversity.",2018 Aug 14,"['Aldunate, Fabián', 'Echeverría, Natalia', 'Chiodi, Daniela', 'López, Pablo', 'Sánchez-Cicerón, Adriana', 'Fajardo, Alvaro', 'Soñora, Martín', 'Cristina, Juan', 'Hernández, Nelia', 'Moreno, Pilar']",Dis Markers,,,True
e52c04caa85880ec10ef5275a67cc3ea3a91a9c1,PMC,Virus and tumor microenvironment induced ER stress and unfolded protein response: from complexity to therapeutics,http://dx.doi.org/10.18632/oncotarget.25886,PMC6112759,30159133,CC BY,"Endoplasmic reticulum (ER) stress can be activated by various pathological and physiological conditions including the unfolded protein response (UPR) to restore homeostasis. The UPR signaling pathways initiated by double-stranded RNA-activated protein kinase (PKR) like ER kinase (PERK), inositol requiring enzyme 1 α (IRE1α), and activating transcription factor 6 (ATF6) are vital for tumor growth, aggressiveness, microenvironment remodeling, and resistance to cancer therapeutics. This review focuses on the role of ER stress and activity of UPR signaling pathways involved in tumor formation and uncontrolled cell proliferation during various cancers and viral malignancies.",2018 Aug 7,"['Asha, Kumari', 'Sharma-Walia, Neelam']",Oncotarget,,,True
e6072267b50da2dfa7595ddd3e29fe99a96d4624,PMC,NADPH Oxidase and Guanylate Binding Protein 5 Restrict Survival of Avirulent Type III Strains of Toxoplasma gondii in Naive Macrophages,http://dx.doi.org/10.1128/mBio.01393-18,PMC6113620,30154263,CC BY,"Phagocytic cells are the first line of innate defense against intracellular pathogens, and yet Toxoplasma gondii is renowned for its ability to survive in macrophages, although this paradigm is based on virulent type I parasites. Surprisingly, we find that avirulent type III parasites are preferentially cleared in naive macrophages, independent of gamma interferon (IFN-γ) activation. The ability of naive macrophages to clear type III parasites was dependent on enhanced activity of NADPH oxidase (Nox)-generated reactive oxygen species (ROS) and induction of guanylate binding protein 5 (Gbp5). Macrophages infected with type III parasites (CTG strain) showed a time-dependent increase in intracellular ROS generation that was higher than that induced by type I parasites (GT1 strain). The absence of Nox1 or Nox2, gp91 subunit isoforms of the Nox complex, reversed ROS-mediated clearance of CTG parasites. Consistent with this finding, both Nox1(−/−) and Nox2(−/−) mice showed higher susceptibility to CTG infection than wild-type mice. Additionally, Gbp5 expression was induced upon infection and the enhanced clearance of CTG strain parasites was reversed in Gbp5(−/−) macrophages. Expression of a type I ROP18 allele in CTG prevented clearance in naive macrophages, suggesting that it plays a role counteracting Gbp5. Although ROS and Gbp5 have been linked to activation of the NLRP3 inflammasome, clearance of CTG parasites did not rely on induction of pyroptosis. Collectively, these findings reveal that not all strains of T. gondii are adept at avoiding clearance in macrophages and define new roles for ROS and Gbps in controlling this important intracellular pathogen.",2018 Aug 28,"['Matta, Sumit K.', 'Patten, Kelley', 'Wang, Quiling', 'Kim, Bae-Hoon', 'MacMicking, John D.', 'Sibley, L. David']",mBio,,,True
9ffdd59ae97f369bdf0202cd78308225f399b3fd,PMC,Catalysts for implementation of One Health in Kenya,http://dx.doi.org/10.11604/pamj.supp.2017.28.1.13275,PMC6113684,30167029,CC BY,"The recent Zika outbreak in the Americas, Ebola epidemic in West Africa and the increased frequency and impact of emerging and re-emerging infections of animal origin have increased the calls for greater preparedness in early detection and responses to public health events. One-Health approaches that emphasize collaborations between human health, animal health and environmental health sectors for the prevention, early detection and response to disease outbreaks have been hailed as a key strategy. Here we highlight three main efforts that have progressed the implementation of One Health in Kenya.",2017 Nov 2,"['Mwatondo, Athman', 'Munyua, Peninah', 'Gura, Zeinab', 'Muturi, Mathew', 'Osoro, Eric', 'Obonyo, Mark', 'Bitek, Austine', 'Oyas, Harry', 'Mbabu, Murithi', 'Kioko, Jackson', 'Njenga, Kariuki', 'Lowther, Sara', 'Thumbi, Samuel Mwangi']",Pan Afr Med J,,,True
159542778cfb78258a07f195a5b4aaf400cdcbcb,PMC,Pathogen seasonality and links with weather in England and Wales: a big data time series analysis,http://dx.doi.org/10.1186/s12889-018-5931-6,PMC6114700,30153803,CC BY,"BACKGROUND: Many infectious diseases of public health importance display annual seasonal patterns in their incidence. We aimed to systematically document the seasonality of several human infectious disease pathogens in England and Wales, highlighting those organisms that appear weather-sensitive and therefore may be influenced by climate change in the future. METHODS: Data on infections in England and Wales from 1989 to 2014 were extracted from the Public Health England (PHE) SGSS surveillance database. We conducted a weekly, monthly and quarterly time series analysis of 277 pathogen serotypes. Each organism’s time series was forecasted using the TBATS package in R, with seasonality detected using model fit statistics. Meteorological data hosted on the MEDMI Platform were extracted at a monthly resolution for 2001–2011. The organisms were then clustered by K-means into two groups based on cross correlation coefficients with the weather variables. RESULTS: Examination of 12.9 million infection episodes found seasonal components in 91/277 (33%) organism serotypes. Salmonella showed seasonal and non-seasonal serotypes. These results were visualised in an online Rshiny application. Seasonal organisms were then clustered into two groups based on their correlations with weather. Group 1 had positive correlations with temperature (max, mean and min), sunshine and vapour pressure and inverse correlations with mean wind speed, relative humidity, ground frost and air frost. Group 2 had the opposite but also slight positive correlations with rainfall (mm, > 1 mm, > 10 mm). CONCLUSIONS: The detection of seasonality in pathogen time series data and the identification of relevant weather predictors can improve forecasting and public health planning. Big data analytics and online visualisation allow the relationship between pathogen incidence and weather patterns to be clarified. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-018-5931-6) contains supplementary material, which is available to authorized users.",2018 Aug 28,"['Cherrie, Mark P. C.', 'Nichols, Gordon', 'Iacono, Gianni Lo', 'Sarran, Christophe', 'Hajat, Shakoor', 'Fleming, Lora E.']",BMC Public Health,,,True
2b36f86d48e438fe97a56febb858af0891328b5d,PMC,Excretion of Eimeria spp. oocysts in young lambs following iron supplementation,http://dx.doi.org/10.1186/s13028-018-0404-6,PMC6114706,30157884,CC BY,"BACKGROUND: Iron is an essential nutrient, and iron supplementation has been shown to reduce the incidence of abomasal bloat in lambs. Additionally, iron deficiency is linked to pica, which may increase uptake of Eimeria oocysts. Coccidiosis in sheep, caused by Eimeria spp., is an important infection, leading to reduced welfare and economic losses. The aims of our study were to investigate: (1) the use of iron supplementation in Norwegian sheep flocks using a questionnaire survey, and (2) whether iron supplementation reduced excretion of Eimeria oocysts and increased the growth rates of young lambs. RESULTS: A questionnaire regarding the use of iron supplementation, sent to all members of the Norwegian Sheep Recording System (n = 4993), showed that 152/1823 farmers iron-supplemented lambs, either orally (56.7%) or by injection (43.3%). The main purpose of supplementation was to prevent abomasal bloat (38.4%), coccidiosis (9.3%), or both (27.8%). In the field study, 102 twin lambs from five flocks were included: one twin (treated) received 600 mg of gleptoferron subcutaneously within 3 days of birth, whereas the control was given saline. McMaster analysis of individual faecal samples obtained at weekly intervals (n = 4 per lamb, starting at turnout) showed no significant difference in oocyst excretion between treatment groups at any sampling, except for one flock 14 days after turnout. Mean growth rates, measured at iron injection, 21 days after turnout, and in the autumn, differed significantly between treated and untreated lambs from iron injection to 21 days after turnout, however, no difference in growth rates was observed in the overall period from iron injection to autumn. Blood analysis suggested that the controls were at risk of developing iron deficiency anaemia during the housed period, but signs of anaemia were not observed. CONCLUSION: Iron supplementation of lambs was used by 8.3% of the farmers responding to the questionnaire, mainly with the intention to prevent abomasal bloat, coccidiosis, or both. The field trial results indicate that iron supplementation of young lambs do not reduce oocyst excretion and only induced a transitory increase in weight gain. However further studies, including more flocks and possibly repeated iron injections, would provide more definitive information. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13028-018-0404-6) contains supplementary material, which is available to authorized users.",2018 Aug 29,"['Odden, Ane', 'Vatn, Synnøve', 'Ruiz, Antonio', 'Robertson, Lucy Jane', 'Enemark, Heidi Larsen', 'Nes, Silje Katrine', 'Tømmerberg, Vibeke', 'Stuen, Snorre']",Acta Vet Scand,,,False
aafce0ff10bc7077faedbbc334c60a1d7021409c,PMC,Excretion of Eimeria spp. oocysts in young lambs following iron supplementation,http://dx.doi.org/10.1186/s13028-018-0404-6,PMC6114706,30157884,CC BY,"BACKGROUND: Iron is an essential nutrient, and iron supplementation has been shown to reduce the incidence of abomasal bloat in lambs. Additionally, iron deficiency is linked to pica, which may increase uptake of Eimeria oocysts. Coccidiosis in sheep, caused by Eimeria spp., is an important infection, leading to reduced welfare and economic losses. The aims of our study were to investigate: (1) the use of iron supplementation in Norwegian sheep flocks using a questionnaire survey, and (2) whether iron supplementation reduced excretion of Eimeria oocysts and increased the growth rates of young lambs. RESULTS: A questionnaire regarding the use of iron supplementation, sent to all members of the Norwegian Sheep Recording System (n = 4993), showed that 152/1823 farmers iron-supplemented lambs, either orally (56.7%) or by injection (43.3%). The main purpose of supplementation was to prevent abomasal bloat (38.4%), coccidiosis (9.3%), or both (27.8%). In the field study, 102 twin lambs from five flocks were included: one twin (treated) received 600 mg of gleptoferron subcutaneously within 3 days of birth, whereas the control was given saline. McMaster analysis of individual faecal samples obtained at weekly intervals (n = 4 per lamb, starting at turnout) showed no significant difference in oocyst excretion between treatment groups at any sampling, except for one flock 14 days after turnout. Mean growth rates, measured at iron injection, 21 days after turnout, and in the autumn, differed significantly between treated and untreated lambs from iron injection to 21 days after turnout, however, no difference in growth rates was observed in the overall period from iron injection to autumn. Blood analysis suggested that the controls were at risk of developing iron deficiency anaemia during the housed period, but signs of anaemia were not observed. CONCLUSION: Iron supplementation of lambs was used by 8.3% of the farmers responding to the questionnaire, mainly with the intention to prevent abomasal bloat, coccidiosis, or both. The field trial results indicate that iron supplementation of young lambs do not reduce oocyst excretion and only induced a transitory increase in weight gain. However further studies, including more flocks and possibly repeated iron injections, would provide more definitive information. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13028-018-0404-6) contains supplementary material, which is available to authorized users.",2018 Aug 29,"['Odden, Ane', 'Vatn, Synnøve', 'Ruiz, Antonio', 'Robertson, Lucy Jane', 'Enemark, Heidi Larsen', 'Nes, Silje Katrine', 'Tømmerberg, Vibeke', 'Stuen, Snorre']",Acta Vet Scand,,,True
fe768cfead153c07c019ac6d722021f035738dc4,PMC,The Accessory Protein ORF3 Contributes to Porcine Epidemic Diarrhea Virus Replication by Direct Binding to the Spike Protein,http://dx.doi.org/10.3390/v10080399,PMC6115756,30060558,CC BY,"The porcine epidemic diarrhea virus (PEDV) is an important swine pathogen responsible for severe watery diarrhea, particularly in neonatal piglets. Despite extensive studies performed to elucidate the function of several viral proteins, the contribution of an accessory protein ORF3 in PEDV replication is still largely unknown. Here, we constructed expression plasmids as well as recombinant PEDV carrying myc-tagged ORF3 to assess their expression and subcellular localization in both transfected and infected cells. In PEDV-infected cells, ORF3 was predominantly localized in the cytoplasm, partially in the endoplasmic reticulum (ER) and the Golgi apparatus (Golgi). Interestingly, ORF3 with the N-terminal Flag tag was also detected on the cell surface concomitant with the spike (S) protein as determined by flow cytometry and confocal microscopy. ORF3 and S proteins were also co-localized at perinuclear compartments and in the vesicle-like structures in transfected and infected cells. We also demonstrated that both full-length and naturally truncated ORF3 proteins could interact with the S protein but with different binding affinity, which correlate with the ability of the protein to regulate virus replication in cell culture. Collectively, our results underscore the unprecedented role of the ORF3, which involves the interaction of ORF3 with S and, possibly, other structural protein during PEDV replication.",2018 Jul 28,"['Kaewborisuth, Challika', 'He, Qigai', 'Jongkaewwattana, Anan']",Viruses,,,True
84158907883b9f76d2a23ab2bc55b0b49173a146,PMC,The Accessory Protein ORF3 Contributes to Porcine Epidemic Diarrhea Virus Replication by Direct Binding to the Spike Protein,http://dx.doi.org/10.3390/v10080399,PMC6115756,30060558,CC BY,"The porcine epidemic diarrhea virus (PEDV) is an important swine pathogen responsible for severe watery diarrhea, particularly in neonatal piglets. Despite extensive studies performed to elucidate the function of several viral proteins, the contribution of an accessory protein ORF3 in PEDV replication is still largely unknown. Here, we constructed expression plasmids as well as recombinant PEDV carrying myc-tagged ORF3 to assess their expression and subcellular localization in both transfected and infected cells. In PEDV-infected cells, ORF3 was predominantly localized in the cytoplasm, partially in the endoplasmic reticulum (ER) and the Golgi apparatus (Golgi). Interestingly, ORF3 with the N-terminal Flag tag was also detected on the cell surface concomitant with the spike (S) protein as determined by flow cytometry and confocal microscopy. ORF3 and S proteins were also co-localized at perinuclear compartments and in the vesicle-like structures in transfected and infected cells. We also demonstrated that both full-length and naturally truncated ORF3 proteins could interact with the S protein but with different binding affinity, which correlate with the ability of the protein to regulate virus replication in cell culture. Collectively, our results underscore the unprecedented role of the ORF3, which involves the interaction of ORF3 with S and, possibly, other structural protein during PEDV replication.",2018 Jul 28,"['Kaewborisuth, Challika', 'He, Qigai', 'Jongkaewwattana, Anan']",Viruses,,,False
2d5a036da3eec69cf318ee695e8bd53347a61a1e,PMC,Redox Biology of Respiratory Viral Infections,http://dx.doi.org/10.3390/v10080392,PMC6115776,30049972,CC BY,"Respiratory viruses cause infections of the upper or lower respiratory tract and they are responsible for the common cold—the most prevalent disease in the world. In many cases the common cold results in severe illness due to complications, such as fever or pneumonia. Children, old people, and immunosuppressed patients are at the highest risk and require fast diagnosis and therapeutic intervention. However, the availability and efficiencies of existing therapeutic approaches vary depending on the virus. Investigation of the pathologies that are associated with infection by respiratory viruses will be paramount for diagnosis, treatment modalities, and the development of new therapies. Changes in redox homeostasis in infected cells are one of the key events that is linked to infection with respiratory viruses and linked to inflammation and subsequent tissue damage. Our review summarizes current knowledge on changes to redox homeostasis, as induced by the different respiratory viruses.",2018 Jul 26,"['Khomich, Olga A.', 'Kochetkov, Sergey N.', 'Bartosch, Birke', 'Ivanov, Alexander V.']",Viruses,,,True
73aec7f72de1b225ab650b78a7633aab4ebd97bc,PMC,The Inhibition of HIV-1 Entry Imposed by Interferon Inducible Transmembrane Proteins Is Independent of Co-Receptor Usage,http://dx.doi.org/10.3390/v10080413,PMC6115839,30087232,CC BY,"Interferon inducible transmembrane proteins (IFITMs) are one of several IFN-stimulated genes (ISGs) that restrict entry of enveloped viruses, including flaviviruses, filoviruses and retroviruses. It has been recently reported that in U87 glioblastoma cells IFITM proteins inhibit HIV-1 entry in a co-receptor-dependent manner, that is, IFITM1 is more inhibitory on CCR5 tropic HIV-1 whereas IFITM2/3 confers a greater suppression of CXCR4 counterparts. However, how entry of HIV-1 with distinct co-receptor usage is modulated by different IFITM orthologs in physiologically relevant CD4(+) T cells and monocytes/macrophages has not been investigated in detail. Here, we report that overexpression of IFITM1, 2 and 3 in human CD4(+) HuT78 cells, SupT1 cells, monocytic THP-1 cells and U87 cells expressing CD4 and co-receptor CCR5 or CXCR4, suppressed entry of CXCR4 tropic viruses NL4.3 and HXB2, CCR5 tropic viruses AD8 and JRFL, dual tropic 89.6 virus, as well as a panel of 32 transmitted founder (T/F) viruses, with a consistent order of potency, that is, IFITM3 > IFITM2 > IFITM1. Consistent with previous reports, we found that some CCR5-using HIV-1 isolates, such as AD8 and JRFL, were relatively resistant to inhibition by IFITM2 and IFITM3, although the effect can be cell-type dependent. However, in no case have we observed that IFITM1 had a stronger inhibition on entry of any HIV-1 strains tested, including those of CCR5-using T/Fs. We knocked down the endogenous IFITMs in peripheral blood mononuclear cells (PBMCs) and purified CD4(+) T cells and observed that, while this treatment did greatly enhance the multiple-round of HIV-1 replication but had modest effect to rescue the single-round HIV-1 infection, reinforcing our previous conclusion that the predominant effect of IFITMs on HIV-1 infection is in viral producer cells, rather than in target cells to block viral entry. Overall, our results argue against the idea that IFITM proteins distinguish co-receptors CCR5 and CXCR4 to inhibit entry but emphasize that the predominant role of IFITMs on HIV-1 is in producer cells that intrinsically impair the viral infectivity.",2018 Aug 7,"['Yu, Jingyou', 'Liu, Shan-Lu']",Viruses,,,True
bbcba5769c3aef1594790aa0d845ba112a0e1ab1,PMC,Low Doses of Ochratoxin-A Decrease IgY and IgA Production in Broiler Chicks,http://dx.doi.org/10.3390/toxins10080316,PMC6115841,30082604,CC BY,"The mycotoxin, ochratoxin-A (OTA), produced by some fungi, and is a natural contaminant of many foods and animal feeds worldwide. Due to its toxic effects, the recommended maximum daily intake of OTA for poultry feeds is 0.1 mg OTA/kg (ECR2006/575/EC); this dose does not induce changes in hepatic/renal parameters, but decreases thymus size and serum globulin concentrations. Accordingly, in this study, we assessed quantitatively the total circulating IgY and IgA serum levels, in chicks consuming a 0.1 mg OTA/kg diet (limit) and higher doses (0.3–1.1 mg OTA/kg diet) for 14 or 21 days. We also evaluated other immunological parameters (thymus, bursa of Fabricius, and spleen weights and leukocyte profiles) at day 21. Decreased IgY serum levels were observed in all OTA-treated groups (p < 0.05). In the low-dose group, IgA levels were decreased on day 21, but not on day 14. The size of the thymus and the bursa of Fabricius was decreased in all OTA-treated groups (p < 0.05), whereas reduced spleen size and altered leukocyte profiles were detected only in the high-dose group (p < 0.05). We concluded that chronic exposure to OTA, even at the recommended highest dose, affected IgY and IgA production in chicks.",2018 Aug 6,"['Khan, Shahzad A.', 'Venancio, Emerson J.', 'Fernandes, Eduardo V.', 'Hirooka, Elisa Y.', 'Oba, Alexandre', 'Flaiban, Karina K. M. C.', 'Itano, Eiko N.']",Toxins (Basel),,,True
360991ff283a6ec08b264813dba65427cecfa615,PMC,Reported Direct and Indirect Contact with Dromedary Camels among Laboratory-Confirmed MERS-CoV Cases,http://dx.doi.org/10.3390/v10080425,PMC6115845,30104551,CC BY,"Dromedary camels (Camelus dromedarius) are now known to be the vertebrate animal reservoir that intermittently transmits the Middle East respiratory syndrome coronavirus (MERS-CoV) to humans. Yet, details as to the specific mechanism(s) of zoonotic transmission from dromedaries to humans remain unclear. The aim of this study was to describe direct and indirect contact with dromedaries among all cases, and then separately for primary, non-primary, and unclassified cases of laboratory-confirmed MERS-CoV reported to the World Health Organization (WHO) between 1 January 2015 and 13 April 2018. We present any reported dromedary contact: direct, indirect, and type of indirect contact. Of all 1125 laboratory-confirmed MERS-CoV cases reported to WHO during the time period, there were 348 (30.9%) primary cases, 455 (40.4%) non-primary cases, and 322 (28.6%) unclassified cases. Among primary cases, 191 (54.9%) reported contact with dromedaries: 164 (47.1%) reported direct contact, 155 (44.5%) reported indirect contact. Five (1.1%) non-primary cases also reported contact with dromedaries. Overall, unpasteurized milk was the most frequent type of dromedary product consumed. Among cases for whom exposure was systematically collected and reported to WHO, contact with dromedaries or dromedary products has played an important role in zoonotic transmission.",2018 Aug 13,"['Conzade, Romy', 'Grant, Rebecca', 'Malik, Mamunur Rahman', 'Elkholy, Amgad', 'Elhakim, Mohamed', 'Samhouri, Dalia', 'Ben Embarek, Peter K.', 'Van Kerkhove, Maria D.']",Viruses,,,True
92c932118ed311b25d35527281e7b8568aeb2dcf,PMC,Suppression of NF-κB Activity: A Viral Immune Evasion Mechanism,http://dx.doi.org/10.3390/v10080409,PMC6115930,30081579,CC BY,"Nuclear factor-κB (NF-κB) is an important transcription factor that induces the expression of antiviral genes and viral genes. NF-κB activation needs the activation of NF-κB upstream molecules, which include receptors, adaptor proteins, NF-κB (IκB) kinases (IKKs), IκBα, and NF-κB dimer p50/p65. To survive, viruses have evolved the capacity to utilize various strategies that inhibit NF-κB activity, including targeting receptors, adaptor proteins, IKKs, IκBα, and p50/p65. To inhibit NF-κB activation, viruses encode several specific NF-κB inhibitors, including NS3/4, 3C and 3C-like proteases, viral deubiquitinating enzymes (DUBs), phosphodegron-like (PDL) motifs, viral protein phosphatase (PPase)-binding proteins, and small hydrophobic (SH) proteins. Finally, we briefly describe the immune evasion mechanism of human immunodeficiency virus 1 (HIV-1) by inhibiting NF-κB activity in productive and latent infections. This paper reviews a viral mechanism of immune evasion that involves the suppression of NF-κB activation to provide new insights into and references for the control and prevention of viral diseases.",2018 Aug 4,"['Deng, Liyao', 'Zeng, Qiurui', 'Wang, Mingshu', 'Cheng, Anchun', 'Jia, Renyong', 'Chen, Shun', 'Zhu, Dekang', 'Liu, Mafeng', 'Yang, Qiao', 'Wu, Ying', 'Zhao, Xinxin', 'Zhang, Shaqiu', 'Liu, Yunya', 'Yu, Yanling', 'Zhang, Ling', 'Chen, Xiaoyue']",Viruses,,,True
786e2292469a024a05dda14af4e9c6ffaa223d75,PMC,Overview of Trends in the Application of Metagenomic Techniques in the Analysis of Human Enteric Viral Diversity in Africa’s Environmental Regimes,http://dx.doi.org/10.3390/v10080429,PMC6115975,30110939,CC BY,"There has been an increase in the quest for metagenomics as an approach for the identification and study of the diversity of human viruses found in aquatic systems, both for their role as waterborne pathogens and as water quality indicators. In the last few years, environmental viral metagenomics has grown significantly and has enabled the identification, diversity and entire genome sequencing of viruses in environmental and clinical samples extensively. Prior to the arrival of metagenomics, traditional molecular procedures such as the polymerase chain reaction (PCR) and sequencing, were mostly used to identify and classify enteric viral species in different environmental milieu. After the advent of metagenomics, more detailed reports have emerged about the important waterborne viruses identified in wastewater treatment plant effluents and surface water. This paper provides a review of methods that have been used for the concentration, detection and identification of viral species from different environmental matrices. The review also takes into consideration where metagenomics has been explored in different African countries, as well as the limitations and challenges facing the approach. Procedures including sample processing, experimental design, sequencing technology, and bioinformatics analysis are discussed. The review concludes by summarising the current thinking and practices in the field and lays bare key issues that those venturing into this field need to consider and address.",2018 Aug 14,"['Osunmakinde, Cecilia Oluseyi', 'Selvarajan, Ramganesh', 'Sibanda, Timothy', 'Mamba, Bhekie B', 'Msagati, Titus A.M']",Viruses,,,True
c9cf89e7642b3da75a33d482d26a330212677479,PMC,Deubiquitinating Enzymes Related to Autophagy: New Therapeutic Opportunities?,http://dx.doi.org/10.3390/cells7080112,PMC6116007,30126257,CC BY,"Autophagy is an evolutionary conserved catabolic process that allows for the degradation of intracellular components by lysosomes. This process can be triggered by nutrient deprivation, microbial infections or other challenges to promote cell survival under these stressed conditions. However, basal levels of autophagy are also crucial for the maintenance of proper cellular homeostasis by ensuring the selective removal of protein aggregates and dysfunctional organelles. A tight regulation of this process is essential for cellular survival and organismal health. Indeed, deregulation of autophagy is associated with a broad range of pathologies such as neuronal degeneration, inflammatory diseases, and cancer progression. Ubiquitination and deubiquitination of autophagy substrates, as well as components of the autophagic machinery, are critical regulatory mechanisms of autophagy. Here, we review the main evidence implicating deubiquitinating enzymes (DUBs) in the regulation of autophagy. We also discuss how they may constitute new therapeutic opportunities in the treatment of pathologies such as cancers, neurodegenerative diseases or infections.",2018 Aug 19,"['Jacomin, Anne-Claire', 'Taillebourg, Emmanuel', 'Fauvarque, Marie-Odile']",Cells,,,True
bb5d7caba7ff8afec3c1fde62cadf65db745ce35,PMC,Shell-Less Egg Syndrome (SES) Widespread in Western Canadian Layer Operations Is Linked to a Massachusetts (Mass) Type Infectious Bronchitis Virus (IBV) Isolate,http://dx.doi.org/10.3390/v10080437,PMC6116215,30126175,CC BY,"A disease with a sudden drop in egg production and shell-less eggs called, shell-less egg syndrome (SES) has been observed in Western Canada egg layer flocks since 2010. The etiology of this disease is not known. We hypothesize that SES is caused by an infectious bronchitis virus (IBV) strain since it is known that IBV replicates in the shell gland causing various eggshell abnormalities. In this study, we screened egg layer flocks, in the provinces of Alberta (AB) and Saskatchewan (SK), with and without a history of SES for the presence of IBV infection. During 2015–2016, a total of 27 egg layer flocks were screened in AB (n = 7) and SK (n = 20). Eighty-one percent of the screened flocks (n = 22) were positive for IBV infection. Thirty of these isolates were successfully characterized using molecular tools targeting the most variable spike (S) 1 gene. IBV isolates from this study clustered into three genotypes based on partial S1 gene variability. The majority of the IBV isolates (70%) were Massachusetts (Mass) type, and the rest were either Connecticut (Conn) type or an uncharacterized genotype with genetic characteristics of Mass and Conn types. Since the majority of the IBV isolates included within the Mass type, we used a Mass type IBV isolate to reproduce SES in specific pathogen free (SPF) white leghorn chickens in lay. Further studies are warranted to investigate whether other IBV isolates can cause SES, to clarify the pathogenesis of SES and to develop a vaccine in order to prevent SES as observed in Western Canadian layer flocks.",2018 Aug 18,"['Amarasinghe, Aruna', 'Popowich, Shelly', 'De Silva Senapathi, Upasama', 'Abdul-Cader, Mohamed Sarjoon', 'Marshall, Frank', 'van der Meer, Frank', 'Cork, Susan C.', 'Gomis, Susantha', 'Abdul-Careem, Mohamed Faizal']",Viruses,,,True
93131e60b42270f064573de0cf5762db42032d7f,PMC,Shell-Less Egg Syndrome (SES) Widespread in Western Canadian Layer Operations Is Linked to a Massachusetts (Mass) Type Infectious Bronchitis Virus (IBV) Isolate,http://dx.doi.org/10.3390/v10080437,PMC6116215,30126175,CC BY,"A disease with a sudden drop in egg production and shell-less eggs called, shell-less egg syndrome (SES) has been observed in Western Canada egg layer flocks since 2010. The etiology of this disease is not known. We hypothesize that SES is caused by an infectious bronchitis virus (IBV) strain since it is known that IBV replicates in the shell gland causing various eggshell abnormalities. In this study, we screened egg layer flocks, in the provinces of Alberta (AB) and Saskatchewan (SK), with and without a history of SES for the presence of IBV infection. During 2015–2016, a total of 27 egg layer flocks were screened in AB (n = 7) and SK (n = 20). Eighty-one percent of the screened flocks (n = 22) were positive for IBV infection. Thirty of these isolates were successfully characterized using molecular tools targeting the most variable spike (S) 1 gene. IBV isolates from this study clustered into three genotypes based on partial S1 gene variability. The majority of the IBV isolates (70%) were Massachusetts (Mass) type, and the rest were either Connecticut (Conn) type or an uncharacterized genotype with genetic characteristics of Mass and Conn types. Since the majority of the IBV isolates included within the Mass type, we used a Mass type IBV isolate to reproduce SES in specific pathogen free (SPF) white leghorn chickens in lay. Further studies are warranted to investigate whether other IBV isolates can cause SES, to clarify the pathogenesis of SES and to develop a vaccine in order to prevent SES as observed in Western Canadian layer flocks.",2018 Aug 18,"['Amarasinghe, Aruna', 'Popowich, Shelly', 'De Silva Senapathi, Upasama', 'Abdul-Cader, Mohamed Sarjoon', 'Marshall, Frank', 'van der Meer, Frank', 'Cork, Susan C.', 'Gomis, Susantha', 'Abdul-Careem, Mohamed Faizal']",Viruses,,,False
54858134e5322fe2b97e39303e832f4b86d07a58,PMC,New Adenovirus Groups in Western Palaearctic Bats,http://dx.doi.org/10.3390/v10080443,PMC6116233,30127258,CC BY,"In the context of long-term screening for viruses on Western Palaearctic bats, we tested for the presence of adenovirus 1392 oropharyngeal swabs and 325 stool samples taken from 27 bat species. Adenoviruses were detected in 12 species of the Vespertilionidae and the Rhinolophidae families. Fifty positive respiratory and 26 positive stool samples were studied. Phylogenetic analyses of partial hexon protein and partial DNA-dependent DNA polymerase genes indicate that all these bat adenoviruses belong to the genus Mastadenovirus but without constituting a monophyletic cluster. According to genetic identities, the new groups are distinct to the previously described Bat mastadenovirus A and B species and contribute with potentially new members. Our data support that diversity of bat mastadenovirus is host-dependent and increase the knowledge of potentially pathogenic virus from bats. Due to the active role of bats as viral reservoirs, the characterization of these viruses is relevant for Public Health.",2018 Aug 20,"['Iglesias-Caballero, Maria', 'Juste, Javier', 'Vázquez-Morón, Sonia', 'Falcon, Ana', 'Aznar-Lopez, Carolina', 'Ibáñez, Carlos', 'Pozo, Francisco', 'Ruiz, Guillermo', 'Berciano, Jose M.', 'Garin, Inazio', 'Aihartza, Joxerra', 'Echevarría, Juan E.', 'Casas, Inmaculada']",Viruses,,,True
78b714501be0196bf41e08915784eef9a6dbfbf3,PMC,New Adenovirus Groups in Western Palaearctic Bats,http://dx.doi.org/10.3390/v10080443,PMC6116233,30127258,CC BY,"In the context of long-term screening for viruses on Western Palaearctic bats, we tested for the presence of adenovirus 1392 oropharyngeal swabs and 325 stool samples taken from 27 bat species. Adenoviruses were detected in 12 species of the Vespertilionidae and the Rhinolophidae families. Fifty positive respiratory and 26 positive stool samples were studied. Phylogenetic analyses of partial hexon protein and partial DNA-dependent DNA polymerase genes indicate that all these bat adenoviruses belong to the genus Mastadenovirus but without constituting a monophyletic cluster. According to genetic identities, the new groups are distinct to the previously described Bat mastadenovirus A and B species and contribute with potentially new members. Our data support that diversity of bat mastadenovirus is host-dependent and increase the knowledge of potentially pathogenic virus from bats. Due to the active role of bats as viral reservoirs, the characterization of these viruses is relevant for Public Health.",2018 Aug 20,"['Iglesias-Caballero, Maria', 'Juste, Javier', 'Vázquez-Morón, Sonia', 'Falcon, Ana', 'Aznar-Lopez, Carolina', 'Ibáñez, Carlos', 'Pozo, Francisco', 'Ruiz, Guillermo', 'Berciano, Jose M.', 'Garin, Inazio', 'Aihartza, Joxerra', 'Echevarría, Juan E.', 'Casas, Inmaculada']",Viruses,,,False
c6ba4dc13c3222eec0dcb0ae56ca8f1261485e96,PMC,Potential Therapeutic Agents for Feline Calicivirus Infection,http://dx.doi.org/10.3390/v10080433,PMC6116245,30115859,CC BY,"Feline calicivirus (FCV) is a major cause of upper respiratory tract disease in cats, with widespread distribution in the feline population. Recently, virulent systemic diseases caused by FCV infection has been associated with mortality rates up to 50%. Currently, there are no direct-acting antivirals approved for the treatment of FCV infection. Here, we tested 15 compounds from different antiviral classes against FCV using in vitro protein and cell culture assays. After the expression of FCV protease-polymerase protein, we established two in vitro assays to assess the inhibitory activity of compounds directly against the FCV protease or polymerase. Using this recombinant enzyme, we identified quercetagetin and PPNDS as inhibitors of FCV polymerase activity (IC(50) values of 2.8 μM and 2.7 μM, respectively). We also demonstrate the inhibition of FCV protease activity by GC376 (IC(50) of 18 µM). Using cell culture assays, PPNDS, quercetagetin and GC376 did not display antivirals effects, however, we identified nitazoxanide and 2′-C-methylcytidine (2CMC) as potent inhibitors of FCV replication, with EC(50) values in the low micromolar range (0.6 μM and 2.5 μM, respectively). In conclusion, we established two in vitro assays that will accelerate the research for FCV antivirals and can be used for the high-throughput screening of direct-acting antivirals.",2018 Aug 16,"['Fumian, Tulio M.', 'Tuipulotu, Daniel Enosi', 'Netzler, Natalie E.', 'Lun, Jennifer H.', 'Russo, Alice G.', 'Yan, Grace J. H.', 'White, Peter A.']",Viruses,,,True
c91fac9f0e239fab524c4595ebf8d0d8a5385f1a,PMC,Deposition of respiratory virus pathogens on frequently touched surfaces at airports,http://dx.doi.org/10.1186/s12879-018-3150-5,PMC6116441,30157776,CC BY,"BACKGROUND: International and national travelling has made the rapid spread of infectious diseases possible. Little information is available on the role of major traffic hubs, such as airports, in the transmission of respiratory infections, including seasonal influenza and a pandemic threat. We investigated the presence of respiratory viruses in the passenger environment of a major airport in order to identify risk points and guide measures to minimize transmission. METHODS: Surface and air samples were collected weekly at three different time points during the peak period of seasonal influenza in 2015–16 in Finland. Swabs from surface samples, and air samples were tested by real-time PCR for influenza A and B viruses, respiratory syncytial virus, adenovirus, rhinovirus and coronaviruses (229E, HKU1, NL63 and OC43). RESULTS: Nucleic acid of at least one respiratory virus was detected in 9 out of 90 (10%) surface samples, including: a plastic toy dog in the children’s playground (2/3 swabs, 67%); hand-carried luggage trays at the security check area (4/8, 50%); the buttons of the payment terminal at the pharmacy (1/2, 50%); the handrails of stairs (1/7, 14%); and the passenger side desk and divider glass at a passport control point (1/3, 33%). Among the 10 respiratory virus findings at various sites, the viruses identified were: rhinovirus (4/10, 40%, from surfaces); coronavirus (3/10, 30%, from surfaces); adenovirus (2/10, 20%, 1 air sample, 1 surface sample); influenza A (1/10, 10%, surface sample). CONCLUSIONS: Detection of pathogen viral nucleic acids indicates respiratory viral surface contamination at multiple sites associated with high touch rates, and suggests a potential risk in the identified airport sites. Of the surfaces tested, plastic security screening trays appeared to pose the highest potential risk, and handling these is almost inevitable for all embarking passengers.",2018 Aug 29,"['Ikonen, Niina', 'Savolainen-Kopra, Carita', 'Enstone, Joanne E.', 'Kulmala, Ilpo', 'Pasanen, Pertti', 'Salmela, Anniina', 'Salo, Satu', 'Nguyen-Van-Tam, Jonathan S.', 'Ruutu, Petri', None]",BMC Infect Dis,,,True
aae5455daa4cc48f51eb989fac34252c045556b8,PMC,Ready for malaria elimination: zero indigenous case reported in the People’s Republic of China,http://dx.doi.org/10.1186/s12936-018-2444-9,PMC6116478,30157876,CC BY,"BACKGROUND: Malaria was once one of the most serious public health problems in China. However, the disease burden has sharply declined and epidemic areas have shrunk after the implementation of an integrated malaria control and elimination strategy, especially since 2000. In this review, the lessons were distilled from the Chinese national malaria elimination programme and further efforts to mitigate the challenges of malaria resurgence are being discussed. METHODS: A retrospective evaluation was performed to assess the changes in malaria epidemic patterns from 1950 to 2017 at national level. The malaria data before 2004 were collected from paper-based annual reports. After 2004, each of the different cases from the Infectious Diseases Information Reporting Management System (IDIRMS) was closely examined and scrutinized. An additional documenting system, the National Information Management System for Malaria, established in 2012 to document the interventions of three parasitic diseases, was also examined to complete the missing data from IDIRMS. RESULTS: From 1950 to 2017, the occurrence of indigenous malaria has been steeply reduced, and malaria-epidemic regions have substantially shrunk, especially after the launch of the national malaria elimination programme. There were approximately 30 million malaria cases annually before 1949 with a mortality rate of 1%. A total of 5999 indigenous cases were documented from 2010 to 2016, with a drastic reduction of 99% over the 6 years (2010, n = 4262; 2016, n = 3). There were indigenous cases reported in 303 counties from 18 provinces in 2010, but only 3 indigenous cases were reported in 2 provinces nationwide in 2016. While in 2017, for the first time, zero indigenous case was reported in China, and only 7 of imported cases were in individuals who died of Plasmodium falciparum infection. CONCLUSION: Malaria elimination in China is a country-led and country-owned endeavour. The country-own efforts were a clear national elimination strategy, supported by two systems, namely a case-based surveillance and response system and reference laboratory system. The country-led efforts were regional and inter-sectoral collaboration as well as sustained monitoring and evaluation. However, there are still some challenges, such as the maintenance of non-transmission status, the implementation of a qualified verification and assessment system, and the management of imported cases in border areas, through regional cooperation. The findings from this review can probably help improving malaria surveillance systems in China, but also in other elimination countries. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12936-018-2444-9) contains supplementary material, which is available to authorized users.",2018 Aug 29,"['Feng, Jun', 'Zhang, Li', 'Huang, Fang', 'Yin, Jian-Hai', 'Tu, Hong', 'Xia, Zhi-Gui', 'Zhou, Shui-Sen', 'Xiao, Ning', 'Zhou, Xiao-Nong']",Malar J,,,True
9984d00caafab39f1c5673c4f7cc53fbddf0b8e9,PMC,A G1-lineage H9N2 virus with oviduct tropism causes chronic pathological changes in the infundibulum and a long-lasting drop in egg production,http://dx.doi.org/10.1186/s13567-018-0575-1,PMC6116506,30157967,CC BY,"Since 1997, G1-lineage H9N2 avian influenza viruses have been circulating in Asia and later on in the Middle East, and they have been associated to mild respiratory disease, drops in egg production and moderate mortality in chickens, in particular in the presence of concurrent infections. In this study, we investigated the importance of the G1-lineage H9N2 A/chicken/Israel/1163/2011 virus as a primary pathogen in layers, analyzing its tropism and binding affinity for the oviduct tissues, and investigating the long-term impact on egg production. Besides causing a mild respiratory infection, the virus replicated in the oviduct of 60% of the hens causing different degrees of salpingitis throughout the organ, in particular at the level of the infundibulum, where the detection of the virus was associated with severe heterophilic infiltrate, and necrosis of the epithelium. Binding affinity assays confirmed that the infundibulum was the most receptive region of the oviduct. The drop in egg production was at its peek at 2 weeks post-infection (pi) (60% decrease) and continued up to 80 days pi (35% decrease). On day 80 pi, non-laying birds showed egg yolk peritonitis, and histopathological analyses described profound alteration of the infundibulum architecture, duct ectasia and thinning of the epithelium, while the rest of the oviduct and ovary appeared normal. Our results show that this H9N2 virus is a primary pathogen in layer hens, and that its replication in the infundibulum is responsible for acute and chronic lesions that limits the effective functionality of the oviduct, compromising the commercial life of birds. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13567-018-0575-1) contains supplementary material, which is available to authorized users.",2018 Aug 29,"['Bonfante, Francesco', 'Mazzetto, Eva', 'Zanardello, Claudia', 'Fortin, Andrea', 'Gobbo, Federica', 'Maniero, Silvia', 'Bigolaro, Michela', 'Davidson, Irit', 'Haddas, Ruth', 'Cattoli, Giovanni', 'Terregino, Calogero']",Vet Res,,,True
fcc66c2bb245f7ddfeccc64ffc5a10013af74a60,PMC,Direct nucleic acid analysis of mosquitoes for high fidelity species identification and detection of Wolbachia using a cellphone,http://dx.doi.org/10.1371/journal.pntd.0006671,PMC6116922,30161131,CC BY,"Manipulation of natural mosquito populations using the endosymbiotic bacteria Wolbachia is being investigated as a novel strategy to reduce the burden of mosquito-borne viruses. To evaluate the efficacy of these interventions, it will be critical to determine Wolbachia infection frequencies in Aedes aegypti mosquito populations. However, current diagnostic tools are not well-suited to fit this need. Morphological methods cannot identify Wolbachia, immunoassays often suffer from low sensitivity and poor throughput, while PCR and spectroscopy require complex instruments and technical expertise, which restrict their use to centralized laboratories. To address this unmet need, we have used loop-mediated isothermal amplification (LAMP) and oligonucleotide strand displacement (OSD) probes to create a one-pot sample-to-answer nucleic acid diagnostic platform for vector and symbiont surveillance. LAMP-OSD assays can directly amplify target nucleic acids from macerated mosquitoes without requiring nucleic acid purification and yield specific single endpoint yes/no fluorescence signals that are observable to eye or by cellphone camera. We demonstrate cellphone-imaged LAMP-OSD tests for two targets, the Aedes aegypti cytochrome oxidase I (coi) gene and the Wolbachia surface protein (wsp) gene, and show a limit of detection of 4 and 40 target DNA copies, respectively. In a blinded test of 90 field-caught mosquitoes, the coi LAMP-OSD assay demonstrated 98% specificity and 97% sensitivity in identifying Ae. aegypti mosquitoes even after 3 weeks of storage without desiccant at 37°C. Similarly, the wsp LAMP-OSD assay readily identified the wAlbB Wolbachia strain in field-collected Aedes albopictus mosquitoes without generating any false positive signals. Modest technology requirements, minimal execution steps, simple binary readout, and robust accuracy make the LAMP-OSD-to-cellphone assay platform well suited for field vector surveillance in austere or resource-limited conditions.",2018 Aug 30,"['Bhadra, Sanchita', 'Riedel, Timothy E.', 'Saldaña, Miguel A.', 'Hegde, Shivanand', 'Pederson, Nicole', 'Hughes, Grant L.', 'Ellington, Andrew D.']",PLoS Negl Trop Dis,,,True
30efef8b0ca9d8d1439685db9abd67608435fab5,PMC,Direct nucleic acid analysis of mosquitoes for high fidelity species identification and detection of Wolbachia using a cellphone,http://dx.doi.org/10.1371/journal.pntd.0006671,PMC6116922,30161131,CC BY,"Manipulation of natural mosquito populations using the endosymbiotic bacteria Wolbachia is being investigated as a novel strategy to reduce the burden of mosquito-borne viruses. To evaluate the efficacy of these interventions, it will be critical to determine Wolbachia infection frequencies in Aedes aegypti mosquito populations. However, current diagnostic tools are not well-suited to fit this need. Morphological methods cannot identify Wolbachia, immunoassays often suffer from low sensitivity and poor throughput, while PCR and spectroscopy require complex instruments and technical expertise, which restrict their use to centralized laboratories. To address this unmet need, we have used loop-mediated isothermal amplification (LAMP) and oligonucleotide strand displacement (OSD) probes to create a one-pot sample-to-answer nucleic acid diagnostic platform for vector and symbiont surveillance. LAMP-OSD assays can directly amplify target nucleic acids from macerated mosquitoes without requiring nucleic acid purification and yield specific single endpoint yes/no fluorescence signals that are observable to eye or by cellphone camera. We demonstrate cellphone-imaged LAMP-OSD tests for two targets, the Aedes aegypti cytochrome oxidase I (coi) gene and the Wolbachia surface protein (wsp) gene, and show a limit of detection of 4 and 40 target DNA copies, respectively. In a blinded test of 90 field-caught mosquitoes, the coi LAMP-OSD assay demonstrated 98% specificity and 97% sensitivity in identifying Ae. aegypti mosquitoes even after 3 weeks of storage without desiccant at 37°C. Similarly, the wsp LAMP-OSD assay readily identified the wAlbB Wolbachia strain in field-collected Aedes albopictus mosquitoes without generating any false positive signals. Modest technology requirements, minimal execution steps, simple binary readout, and robust accuracy make the LAMP-OSD-to-cellphone assay platform well suited for field vector surveillance in austere or resource-limited conditions.",2018 Aug 30,"['Bhadra, Sanchita', 'Riedel, Timothy E.', 'Saldaña, Miguel A.', 'Hegde, Shivanand', 'Pederson, Nicole', 'Hughes, Grant L.', 'Ellington, Andrew D.']",PLoS Negl Trop Dis,,,False
d9f32c5d8e52070d45fbe1974c19afd95390046e,PMC,Direct nucleic acid analysis of mosquitoes for high fidelity species identification and detection of Wolbachia using a cellphone,http://dx.doi.org/10.1371/journal.pntd.0006671,PMC6116922,30161131,CC BY,"Manipulation of natural mosquito populations using the endosymbiotic bacteria Wolbachia is being investigated as a novel strategy to reduce the burden of mosquito-borne viruses. To evaluate the efficacy of these interventions, it will be critical to determine Wolbachia infection frequencies in Aedes aegypti mosquito populations. However, current diagnostic tools are not well-suited to fit this need. Morphological methods cannot identify Wolbachia, immunoassays often suffer from low sensitivity and poor throughput, while PCR and spectroscopy require complex instruments and technical expertise, which restrict their use to centralized laboratories. To address this unmet need, we have used loop-mediated isothermal amplification (LAMP) and oligonucleotide strand displacement (OSD) probes to create a one-pot sample-to-answer nucleic acid diagnostic platform for vector and symbiont surveillance. LAMP-OSD assays can directly amplify target nucleic acids from macerated mosquitoes without requiring nucleic acid purification and yield specific single endpoint yes/no fluorescence signals that are observable to eye or by cellphone camera. We demonstrate cellphone-imaged LAMP-OSD tests for two targets, the Aedes aegypti cytochrome oxidase I (coi) gene and the Wolbachia surface protein (wsp) gene, and show a limit of detection of 4 and 40 target DNA copies, respectively. In a blinded test of 90 field-caught mosquitoes, the coi LAMP-OSD assay demonstrated 98% specificity and 97% sensitivity in identifying Ae. aegypti mosquitoes even after 3 weeks of storage without desiccant at 37°C. Similarly, the wsp LAMP-OSD assay readily identified the wAlbB Wolbachia strain in field-collected Aedes albopictus mosquitoes without generating any false positive signals. Modest technology requirements, minimal execution steps, simple binary readout, and robust accuracy make the LAMP-OSD-to-cellphone assay platform well suited for field vector surveillance in austere or resource-limited conditions.",2018 Aug 30,"['Bhadra, Sanchita', 'Riedel, Timothy E.', 'Saldaña, Miguel A.', 'Hegde, Shivanand', 'Pederson, Nicole', 'Hughes, Grant L.', 'Ellington, Andrew D.']",PLoS Negl Trop Dis,,,False
f2826f841109cdf262e7381d4b7a19376936b18a,PMC,Direct nucleic acid analysis of mosquitoes for high fidelity species identification and detection of Wolbachia using a cellphone,http://dx.doi.org/10.1371/journal.pntd.0006671,PMC6116922,30161131,CC BY,"Manipulation of natural mosquito populations using the endosymbiotic bacteria Wolbachia is being investigated as a novel strategy to reduce the burden of mosquito-borne viruses. To evaluate the efficacy of these interventions, it will be critical to determine Wolbachia infection frequencies in Aedes aegypti mosquito populations. However, current diagnostic tools are not well-suited to fit this need. Morphological methods cannot identify Wolbachia, immunoassays often suffer from low sensitivity and poor throughput, while PCR and spectroscopy require complex instruments and technical expertise, which restrict their use to centralized laboratories. To address this unmet need, we have used loop-mediated isothermal amplification (LAMP) and oligonucleotide strand displacement (OSD) probes to create a one-pot sample-to-answer nucleic acid diagnostic platform for vector and symbiont surveillance. LAMP-OSD assays can directly amplify target nucleic acids from macerated mosquitoes without requiring nucleic acid purification and yield specific single endpoint yes/no fluorescence signals that are observable to eye or by cellphone camera. We demonstrate cellphone-imaged LAMP-OSD tests for two targets, the Aedes aegypti cytochrome oxidase I (coi) gene and the Wolbachia surface protein (wsp) gene, and show a limit of detection of 4 and 40 target DNA copies, respectively. In a blinded test of 90 field-caught mosquitoes, the coi LAMP-OSD assay demonstrated 98% specificity and 97% sensitivity in identifying Ae. aegypti mosquitoes even after 3 weeks of storage without desiccant at 37°C. Similarly, the wsp LAMP-OSD assay readily identified the wAlbB Wolbachia strain in field-collected Aedes albopictus mosquitoes without generating any false positive signals. Modest technology requirements, minimal execution steps, simple binary readout, and robust accuracy make the LAMP-OSD-to-cellphone assay platform well suited for field vector surveillance in austere or resource-limited conditions.",2018 Aug 30,"['Bhadra, Sanchita', 'Riedel, Timothy E.', 'Saldaña, Miguel A.', 'Hegde, Shivanand', 'Pederson, Nicole', 'Hughes, Grant L.', 'Ellington, Andrew D.']",PLoS Negl Trop Dis,,,False
2d4ff6dc45717234b555ea8d5376c2cf29edeb1a,PMC,Direct nucleic acid analysis of mosquitoes for high fidelity species identification and detection of Wolbachia using a cellphone,http://dx.doi.org/10.1371/journal.pntd.0006671,PMC6116922,30161131,CC BY,"Manipulation of natural mosquito populations using the endosymbiotic bacteria Wolbachia is being investigated as a novel strategy to reduce the burden of mosquito-borne viruses. To evaluate the efficacy of these interventions, it will be critical to determine Wolbachia infection frequencies in Aedes aegypti mosquito populations. However, current diagnostic tools are not well-suited to fit this need. Morphological methods cannot identify Wolbachia, immunoassays often suffer from low sensitivity and poor throughput, while PCR and spectroscopy require complex instruments and technical expertise, which restrict their use to centralized laboratories. To address this unmet need, we have used loop-mediated isothermal amplification (LAMP) and oligonucleotide strand displacement (OSD) probes to create a one-pot sample-to-answer nucleic acid diagnostic platform for vector and symbiont surveillance. LAMP-OSD assays can directly amplify target nucleic acids from macerated mosquitoes without requiring nucleic acid purification and yield specific single endpoint yes/no fluorescence signals that are observable to eye or by cellphone camera. We demonstrate cellphone-imaged LAMP-OSD tests for two targets, the Aedes aegypti cytochrome oxidase I (coi) gene and the Wolbachia surface protein (wsp) gene, and show a limit of detection of 4 and 40 target DNA copies, respectively. In a blinded test of 90 field-caught mosquitoes, the coi LAMP-OSD assay demonstrated 98% specificity and 97% sensitivity in identifying Ae. aegypti mosquitoes even after 3 weeks of storage without desiccant at 37°C. Similarly, the wsp LAMP-OSD assay readily identified the wAlbB Wolbachia strain in field-collected Aedes albopictus mosquitoes without generating any false positive signals. Modest technology requirements, minimal execution steps, simple binary readout, and robust accuracy make the LAMP-OSD-to-cellphone assay platform well suited for field vector surveillance in austere or resource-limited conditions.",2018 Aug 30,"['Bhadra, Sanchita', 'Riedel, Timothy E.', 'Saldaña, Miguel A.', 'Hegde, Shivanand', 'Pederson, Nicole', 'Hughes, Grant L.', 'Ellington, Andrew D.']",PLoS Negl Trop Dis,,,False
e1ad3f81e2da8917381acd7a3190264cc856aae2,PMC,Direct nucleic acid analysis of mosquitoes for high fidelity species identification and detection of Wolbachia using a cellphone,http://dx.doi.org/10.1371/journal.pntd.0006671,PMC6116922,30161131,CC BY,"Manipulation of natural mosquito populations using the endosymbiotic bacteria Wolbachia is being investigated as a novel strategy to reduce the burden of mosquito-borne viruses. To evaluate the efficacy of these interventions, it will be critical to determine Wolbachia infection frequencies in Aedes aegypti mosquito populations. However, current diagnostic tools are not well-suited to fit this need. Morphological methods cannot identify Wolbachia, immunoassays often suffer from low sensitivity and poor throughput, while PCR and spectroscopy require complex instruments and technical expertise, which restrict their use to centralized laboratories. To address this unmet need, we have used loop-mediated isothermal amplification (LAMP) and oligonucleotide strand displacement (OSD) probes to create a one-pot sample-to-answer nucleic acid diagnostic platform for vector and symbiont surveillance. LAMP-OSD assays can directly amplify target nucleic acids from macerated mosquitoes without requiring nucleic acid purification and yield specific single endpoint yes/no fluorescence signals that are observable to eye or by cellphone camera. We demonstrate cellphone-imaged LAMP-OSD tests for two targets, the Aedes aegypti cytochrome oxidase I (coi) gene and the Wolbachia surface protein (wsp) gene, and show a limit of detection of 4 and 40 target DNA copies, respectively. In a blinded test of 90 field-caught mosquitoes, the coi LAMP-OSD assay demonstrated 98% specificity and 97% sensitivity in identifying Ae. aegypti mosquitoes even after 3 weeks of storage without desiccant at 37°C. Similarly, the wsp LAMP-OSD assay readily identified the wAlbB Wolbachia strain in field-collected Aedes albopictus mosquitoes without generating any false positive signals. Modest technology requirements, minimal execution steps, simple binary readout, and robust accuracy make the LAMP-OSD-to-cellphone assay platform well suited for field vector surveillance in austere or resource-limited conditions.",2018 Aug 30,"['Bhadra, Sanchita', 'Riedel, Timothy E.', 'Saldaña, Miguel A.', 'Hegde, Shivanand', 'Pederson, Nicole', 'Hughes, Grant L.', 'Ellington, Andrew D.']",PLoS Negl Trop Dis,,,False
f08a40c25b57899964bb15786c03694fbdafa5d7,PMC,Direct nucleic acid analysis of mosquitoes for high fidelity species identification and detection of Wolbachia using a cellphone,http://dx.doi.org/10.1371/journal.pntd.0006671,PMC6116922,30161131,CC BY,"Manipulation of natural mosquito populations using the endosymbiotic bacteria Wolbachia is being investigated as a novel strategy to reduce the burden of mosquito-borne viruses. To evaluate the efficacy of these interventions, it will be critical to determine Wolbachia infection frequencies in Aedes aegypti mosquito populations. However, current diagnostic tools are not well-suited to fit this need. Morphological methods cannot identify Wolbachia, immunoassays often suffer from low sensitivity and poor throughput, while PCR and spectroscopy require complex instruments and technical expertise, which restrict their use to centralized laboratories. To address this unmet need, we have used loop-mediated isothermal amplification (LAMP) and oligonucleotide strand displacement (OSD) probes to create a one-pot sample-to-answer nucleic acid diagnostic platform for vector and symbiont surveillance. LAMP-OSD assays can directly amplify target nucleic acids from macerated mosquitoes without requiring nucleic acid purification and yield specific single endpoint yes/no fluorescence signals that are observable to eye or by cellphone camera. We demonstrate cellphone-imaged LAMP-OSD tests for two targets, the Aedes aegypti cytochrome oxidase I (coi) gene and the Wolbachia surface protein (wsp) gene, and show a limit of detection of 4 and 40 target DNA copies, respectively. In a blinded test of 90 field-caught mosquitoes, the coi LAMP-OSD assay demonstrated 98% specificity and 97% sensitivity in identifying Ae. aegypti mosquitoes even after 3 weeks of storage without desiccant at 37°C. Similarly, the wsp LAMP-OSD assay readily identified the wAlbB Wolbachia strain in field-collected Aedes albopictus mosquitoes without generating any false positive signals. Modest technology requirements, minimal execution steps, simple binary readout, and robust accuracy make the LAMP-OSD-to-cellphone assay platform well suited for field vector surveillance in austere or resource-limited conditions.",2018 Aug 30,"['Bhadra, Sanchita', 'Riedel, Timothy E.', 'Saldaña, Miguel A.', 'Hegde, Shivanand', 'Pederson, Nicole', 'Hughes, Grant L.', 'Ellington, Andrew D.']",PLoS Negl Trop Dis,,,False
df3b4d6bbca2f3984a538ee4418f52fb96ed2aa9,PMC,Direct nucleic acid analysis of mosquitoes for high fidelity species identification and detection of Wolbachia using a cellphone,http://dx.doi.org/10.1371/journal.pntd.0006671,PMC6116922,30161131,CC BY,"Manipulation of natural mosquito populations using the endosymbiotic bacteria Wolbachia is being investigated as a novel strategy to reduce the burden of mosquito-borne viruses. To evaluate the efficacy of these interventions, it will be critical to determine Wolbachia infection frequencies in Aedes aegypti mosquito populations. However, current diagnostic tools are not well-suited to fit this need. Morphological methods cannot identify Wolbachia, immunoassays often suffer from low sensitivity and poor throughput, while PCR and spectroscopy require complex instruments and technical expertise, which restrict their use to centralized laboratories. To address this unmet need, we have used loop-mediated isothermal amplification (LAMP) and oligonucleotide strand displacement (OSD) probes to create a one-pot sample-to-answer nucleic acid diagnostic platform for vector and symbiont surveillance. LAMP-OSD assays can directly amplify target nucleic acids from macerated mosquitoes without requiring nucleic acid purification and yield specific single endpoint yes/no fluorescence signals that are observable to eye or by cellphone camera. We demonstrate cellphone-imaged LAMP-OSD tests for two targets, the Aedes aegypti cytochrome oxidase I (coi) gene and the Wolbachia surface protein (wsp) gene, and show a limit of detection of 4 and 40 target DNA copies, respectively. In a blinded test of 90 field-caught mosquitoes, the coi LAMP-OSD assay demonstrated 98% specificity and 97% sensitivity in identifying Ae. aegypti mosquitoes even after 3 weeks of storage without desiccant at 37°C. Similarly, the wsp LAMP-OSD assay readily identified the wAlbB Wolbachia strain in field-collected Aedes albopictus mosquitoes without generating any false positive signals. Modest technology requirements, minimal execution steps, simple binary readout, and robust accuracy make the LAMP-OSD-to-cellphone assay platform well suited for field vector surveillance in austere or resource-limited conditions.",2018 Aug 30,"['Bhadra, Sanchita', 'Riedel, Timothy E.', 'Saldaña, Miguel A.', 'Hegde, Shivanand', 'Pederson, Nicole', 'Hughes, Grant L.', 'Ellington, Andrew D.']",PLoS Negl Trop Dis,,,False
ab39d4f77fdd2018abd5d3a223042656993781cc,PMC,Direct nucleic acid analysis of mosquitoes for high fidelity species identification and detection of Wolbachia using a cellphone,http://dx.doi.org/10.1371/journal.pntd.0006671,PMC6116922,30161131,CC BY,"Manipulation of natural mosquito populations using the endosymbiotic bacteria Wolbachia is being investigated as a novel strategy to reduce the burden of mosquito-borne viruses. To evaluate the efficacy of these interventions, it will be critical to determine Wolbachia infection frequencies in Aedes aegypti mosquito populations. However, current diagnostic tools are not well-suited to fit this need. Morphological methods cannot identify Wolbachia, immunoassays often suffer from low sensitivity and poor throughput, while PCR and spectroscopy require complex instruments and technical expertise, which restrict their use to centralized laboratories. To address this unmet need, we have used loop-mediated isothermal amplification (LAMP) and oligonucleotide strand displacement (OSD) probes to create a one-pot sample-to-answer nucleic acid diagnostic platform for vector and symbiont surveillance. LAMP-OSD assays can directly amplify target nucleic acids from macerated mosquitoes without requiring nucleic acid purification and yield specific single endpoint yes/no fluorescence signals that are observable to eye or by cellphone camera. We demonstrate cellphone-imaged LAMP-OSD tests for two targets, the Aedes aegypti cytochrome oxidase I (coi) gene and the Wolbachia surface protein (wsp) gene, and show a limit of detection of 4 and 40 target DNA copies, respectively. In a blinded test of 90 field-caught mosquitoes, the coi LAMP-OSD assay demonstrated 98% specificity and 97% sensitivity in identifying Ae. aegypti mosquitoes even after 3 weeks of storage without desiccant at 37°C. Similarly, the wsp LAMP-OSD assay readily identified the wAlbB Wolbachia strain in field-collected Aedes albopictus mosquitoes without generating any false positive signals. Modest technology requirements, minimal execution steps, simple binary readout, and robust accuracy make the LAMP-OSD-to-cellphone assay platform well suited for field vector surveillance in austere or resource-limited conditions.",2018 Aug 30,"['Bhadra, Sanchita', 'Riedel, Timothy E.', 'Saldaña, Miguel A.', 'Hegde, Shivanand', 'Pederson, Nicole', 'Hughes, Grant L.', 'Ellington, Andrew D.']",PLoS Negl Trop Dis,,,False
bf63f2e34138691d31b1282fe9cf47423c5f5a8a,PMC,The antiparasitic drug niclosamide inhibits dengue virus infection by interfering with endosomal acidification independent of mTOR,http://dx.doi.org/10.1371/journal.pntd.0006715,PMC6117097,30125275,CC BY,"BACKGROUND: The antiparasitic agent niclosamide has been demonstrated to inhibit the arthropod-borne Zika virus. Here, we investigated the antiviral capacity of niclosamide against dengue virus (DENV) serotype 2 infection in vitro and in vivo. PRINCIPLE FINDING: Niclosamide effectively retarded DENV-induced infection in vitro in human adenocarcinoma cells (A549), mouse neuroblastoma cells (Neuro-2a), and baby hamster kidney fibroblasts (BHK-21). Treatment with niclosamide did not retard the endocytosis of DENV while niclosamide was unable to enhance the antiviral type I interferon response. Furthermore, niclosamide did not cause a direct effect on viral replicon-based expression. Niclosamide has been reported to competitively inhibit the mTOR (mammalian target of rapamycin), STAT3 (signal transducer and activator of transcription 3), and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathways; however, selective inhibitors of those pathways did not reduce DENV infection. Similar to the vacuolar-type H(+)-ATPase inhibitor bafilomycin A1, both niclosamide and other protonophores, such as CCCP (carbonyl cyanide m-chlorophenyl hydrazone), and FCCP (carbonyl cyanide-p-trifluoromethoxyphenylhydrazone), effectively reduced endosomal acidification and viral dsRNA replication. Co-administration of a single dose of niclosamide partially decreased viral replication, viral encephalitis, and mortality in DENV-infected ICR suckling mice. SIGNIFICANCE: These results demonstrate that niclosamide diminishes viral infection by hindering endosomal acidification.",2018 Aug 20,"['Kao, Jo-Chi', 'HuangFu, Wei-Chun', 'Tsai, Tsung-Ting', 'Ho, Min-Ru', 'Jhan, Ming-Kai', 'Shen, Ting-Jing', 'Tseng, Po-Chun', 'Wang, Yung-Ting', 'Lin, Chiou-Feng']",PLoS Negl Trop Dis,,,True
f488237187c7b67ffdf93185574e610b8c7cc999,PMC,A Versatile Sample Processing Workflow for Metagenomic Pathogen Detection,http://dx.doi.org/10.1038/s41598-018-31496-1,PMC6117295,30166611,CC BY,"Metagenomics is currently the only generic method for pathogen detection. Starting from RNA allows the assessment of the whole sample community including RNA viruses. Here we present our modular concerted protocol for sample processing for diagnostic metagenomics analysis of human, animal, and food samples. The workflow does not rely on dedicated amplification steps at any stage in the process and, in contrast to published methods, libraries prepared accordingly will yield only minute amounts of unclassifiable reads. We confirmed the performance of the approach using a spectrum of pathogen/matrix-combinations showing it has the potential to become a commonly usable analytical framework.",2018 Aug 30,"['Wylezich, Claudia', 'Papa, Anna', 'Beer, Martin', 'Höper, Dirk']",Sci Rep,,,True
3929d5fe37521db29b4d747ab3c9376f6865be16,PMC,A Versatile Sample Processing Workflow for Metagenomic Pathogen Detection,http://dx.doi.org/10.1038/s41598-018-31496-1,PMC6117295,30166611,CC BY,"Metagenomics is currently the only generic method for pathogen detection. Starting from RNA allows the assessment of the whole sample community including RNA viruses. Here we present our modular concerted protocol for sample processing for diagnostic metagenomics analysis of human, animal, and food samples. The workflow does not rely on dedicated amplification steps at any stage in the process and, in contrast to published methods, libraries prepared accordingly will yield only minute amounts of unclassifiable reads. We confirmed the performance of the approach using a spectrum of pathogen/matrix-combinations showing it has the potential to become a commonly usable analytical framework.",2018 Aug 30,"['Wylezich, Claudia', 'Papa, Anna', 'Beer, Martin', 'Höper, Dirk']",Sci Rep,,,True
812cc3ff2d36c2d370f943c6fd0d2d45b918296e,PMC,Segmented Filamentous Bacteria – Metabolism Meets Immunity,http://dx.doi.org/10.3389/fmicb.2018.01991,PMC6117376,30197636,CC BY,"Segmented filamentous bacteria (SFB) are a group of host-adapted, commensal organisms that attach to the ileal epithelium of vertebrate and invertebrate hosts. A genetic relative of the genus Clostridium, these morphologically unique bacteria display a replication and differentiation lifecycle initiated by epithelial tissue binding and filamentation. SFB intimately bind to the surface of absorptive intestinal epithelium without inducing an inflammatory response. Rather, their presence impacts the generation of innate and differentiation of acquired immunity, which impact the clearance of extracellular bacterial or fungal pathogens in the gastrointestinal and respiratory tracts. SFB have recently garnered attention due to their role in promoting adaptive and innate immunity in mice and rats through the differentiation and maturation of Th17 cells in the intestinal tract and production of immunoglobulin A (IgA). SFB are the first commensal bacteria identified that impact the maturation and development of Th17 cells in mice. Recently, microbiome studies have revealed the presence of Candidatus Arthromitus (occasionally designated as Candidatus Savagella), a proposed candidate species of SFB, in higher proportions in higher-performing flocks as compared to matched lower-performing flocks, suggesting that SFB may serve to establish a healthy gut and protect commercial turkeys from pathogens resulting in morbidity and decreased performance. In this review we seek to describe the life cycle, host specificity, and genetic capabilities of SFB, such as bacterial metabolism, and how these factors influence the host immunity and microbiome. Although the role of SFB to induce antigen-specific Th17 cells in poultry is unknown, they may play an important role in modulating the immune response in the intestinal tract to promote resistance against some infectious diseases and promote food-safety. This review demonstrates the importance of studying and further characterizing commensal, host-specific bacteria in food-producing animals and their importance to animal health.",2018 Aug 24,"['Hedblom, Grant A.', 'Reiland, Holly A.', 'Sylte, Matthew J.', 'Johnson, Timothy J.', 'Baumler, David J.']",Front Microbiol,,,True
5e0c586f047ff909c8ed3fe171c8975a90608d08,PMC,Neutralizing antibodies against porcine epidemic diarrhea virus block virus attachment and internalization,http://dx.doi.org/10.1186/s12985-018-1042-3,PMC6117962,30165871,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is emerging as a pathogenic coronavirus that causes a huge economic burden to the swine industry. Interaction of the viral spike (S) surface glycoprotein with the host cell receptor is recognized as the first step of infection and is the main determinant of virus tropism. The mechanisms by which neutralizing antibodies inhibit PEDV have not been defined. Isolating PEDV neutralizing antibodies are crucial to identifying the receptor-binding domains of the viral spike and elucidating the mechanism of protection against PEDV infection. METHODS: B cell hybridoma technique was used to generate hybridoma cells that secrete specific antibodies. E.coli prokaryotic expression system and Bac-to-Bac expression system were used to identify the target protein of each monoclonal antibody. qPCR was performed to analyze PEDV binding to Vero E6 cells with neutralizing antibody. RESULTS: We identified 10 monoclonal antibodies using hybridoma technology. Remarkably, 4 mAbs (designed 2G8, 2B11, 3D9, 1E3) neutralized virus infection potently, of which 2B11 and 1E3 targeted the conformational epitope of the PEDV S protein. qPCR results showed that both 2B11 and 2G8 blocked virus entry into Vero cells. CONCLUSION: The data suggested that PEDV neutralizing antibody inhibited virus infection by binding to infectious virions, which could work as a tool to find the receptor-binding domains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1042-3) contains supplementary material, which is available to authorized users.",2018 Aug 30,"['Gong, Lang', 'Lin, Ying', 'Qin, Jianru', 'Li, Qianniu', 'Xue, Chunyi', 'Cao, Yongchang']",Virol J,,,True
2b2ec303d28afd9e460b710dd23efe264a5359f0,PMC,Polarized Entry of Human Parechoviruses in the Airway Epithelium,http://dx.doi.org/10.3389/fcimb.2018.00294,PMC6119779,30211126,CC BY,"Human parechoviruses (HPeVs), a poorly studied genus within the Picornaviridae family, are classified into 19 genotypes of which HPeV1 and HPeV3 are the most often detected. HPeV1 VP1 C terminus contains an arginine-glycine-aspartic acid (RGD) motif and has been shown to depend on the host cell surface αV integrins (αV ITGs) and heparan sulfate (HS) for entry. HPeV3 lacks this motif and the receptors remain unknown. HPeVs can be detected in patient nasopharyngeal and stool samples, and infection is presumed to occur after respiratory or gastro-intestinal transmission. HPeV pathogenesis is poorly understood as there are no animal models and previous studies have been conducted in immortalized monolayer cell cultures which do not adequately represent the characteristics of human tissues. To bridge this gap, we determined the polarity of infection, replication kinetics, and cell tropism of HPeV1 and HPeV3 in the well-differentiated human airway epithelial (HAE) model. We found the HAE cultures to be permissive for HPeVs. Both HPeV genotypes infected the HAE preferentially from the basolateral surface while the progeny virus was shed toward the apical side. Confocal microscopy revealed the target cell type to be the p63(+) basal cells for both viruses, αV ITG and HS blocking had no effect on the replication of either virus, and transcriptional profiling suggested that HPeV3 infection induced stronger immune activation than HPeV1. Genotype-specific host responses may contribute to the differences in pathogenesis and clinical outcomes associated with HPeV1 and HPeV3.",2018 Aug 22,"['Karelehto, Eveliina', 'Cristella, Cosimo', 'Yu, Xiao', 'Sridhar, Adithya', 'Hulsdouw, Rens', 'de Haan, Karen', 'van Eijk, Hetty', 'Koekkoek, Sylvie', 'Pajkrt, Dasja', 'de Jong, Menno D.', 'Wolthers, Katja C.']",Front Cell Infect Microbiol,,,True
1b6424319439d316bcc6a1f8f6eb814fbff3129d,PMC,Containment measures for emerging and re-emerging vector-borne and other infectious diseases of poverty in urban settings: a scoping review,http://dx.doi.org/10.1186/s40249-018-0478-4,PMC6120079,30173673,CC BY,"BACKGROUND: The emergence and re-emergence of vector-borne and other infectious diseases of poverty pose a threat to the health of populations living in urban and low-income settings. A detailed understanding of intervention strategies, including effectiveness of past outbreak containment, is necessary to improve future practices. The objective was to determine what is known about the effectiveness of containment measures for emerging and re-emerging vector-borne and other infectious diseases of poverty in urban settings and identify research gaps and implications for public health practice. MAIN BODY: We conducted a scoping review and systematically searched peer-reviewed and grey literature published between 2000 and 2016. Different data extraction tools were used for data coding and extraction, and data on implementation process and transferability were extracted from all studies. A quality assessment was conducted for each included study. We screened 205 full-text articles and reports for a total of 31 articles included in the review. The quality of the studies was generally low to moderate. The largest body of evidence concerned control activities for Ebola virus and dengue fever. The majority of interventions (87%) relied on multiple types of measures, which were grouped into four categories: 1) healthcare provision; 2) epidemiological investigation and/or surveillance; 3) environmental or sanitary interventions; and 4) community-based interventions. The quality of the majority of studies (90%) was poor or moderate, and one-third of the studies did not provide a clear description of the outcomes and of the procedures and/or tools used for the intervention. CONCLUSIONS: Our results highlight the difficulty of establishing causation when assessing the effect of containment measures. Studies that extend beyond solely reporting on effectiveness and take into account the complexity of real-world settings are urgently needed. We recommend the allocation of research efforts to the evaluation of the implementation processes of interventions as well as their comprehensive and systematic description using validated checklists. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-018-0478-4) contains supplementary material, which is available to authorized users.",2018 Sep 3,"['Campeau, Laurence', 'Degroote, Stéphanie', 'Ridde, Valery', 'Carabali, Mabel', 'Zinszer, Kate']",Infect Dis Poverty,,,False
a336fd69f73d0debd55b454b97ff45cf9f39d82a,PMC,Containment measures for emerging and re-emerging vector-borne and other infectious diseases of poverty in urban settings: a scoping review,http://dx.doi.org/10.1186/s40249-018-0478-4,PMC6120079,30173673,CC BY,"BACKGROUND: The emergence and re-emergence of vector-borne and other infectious diseases of poverty pose a threat to the health of populations living in urban and low-income settings. A detailed understanding of intervention strategies, including effectiveness of past outbreak containment, is necessary to improve future practices. The objective was to determine what is known about the effectiveness of containment measures for emerging and re-emerging vector-borne and other infectious diseases of poverty in urban settings and identify research gaps and implications for public health practice. MAIN BODY: We conducted a scoping review and systematically searched peer-reviewed and grey literature published between 2000 and 2016. Different data extraction tools were used for data coding and extraction, and data on implementation process and transferability were extracted from all studies. A quality assessment was conducted for each included study. We screened 205 full-text articles and reports for a total of 31 articles included in the review. The quality of the studies was generally low to moderate. The largest body of evidence concerned control activities for Ebola virus and dengue fever. The majority of interventions (87%) relied on multiple types of measures, which were grouped into four categories: 1) healthcare provision; 2) epidemiological investigation and/or surveillance; 3) environmental or sanitary interventions; and 4) community-based interventions. The quality of the majority of studies (90%) was poor or moderate, and one-third of the studies did not provide a clear description of the outcomes and of the procedures and/or tools used for the intervention. CONCLUSIONS: Our results highlight the difficulty of establishing causation when assessing the effect of containment measures. Studies that extend beyond solely reporting on effectiveness and take into account the complexity of real-world settings are urgently needed. We recommend the allocation of research efforts to the evaluation of the implementation processes of interventions as well as their comprehensive and systematic description using validated checklists. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-018-0478-4) contains supplementary material, which is available to authorized users.",2018 Sep 3,"['Campeau, Laurence', 'Degroote, Stéphanie', 'Ridde, Valery', 'Carabali, Mabel', 'Zinszer, Kate']",Infect Dis Poverty,,,True
620c2d071dd49eb5bcc31f378eb219310e4b1ebc,PMC,MicroR‐9‐5p suppresses EV71 replication through targeting NFκB of the RIG‐I‐mediated innate immune response,http://dx.doi.org/10.1002/2211-5463.12490,PMC6120239,30186747,CC BY,"Accumulating evidence demonstrates that there is a causative link between hsa‐microRNA‐9‐5p (miR‐9) and pathophysiological processes. Enterovirus 71 (EV71) has been found to contribute to numerous severe clinical symptoms which result in death. The exact mechanism by which EV71 influences miR‐9 expression is unknown, and the relationship between miR‐9 and EV71 is still unclear. Here, miR‐9 expression was found to be impaired upon EV71 infection in several cell lines and in an EV71 infection mouse model. Additionally, we confirmed that EV71 infection induces robust expression of pro‐inflammatory cytokines (TNF‐α, IL‐6, and IL‐1) and interferons (IFN‐α and IFN‐β). Overexpression of miR‐9 attenuated EV71 proliferation and reduced protein and gene expressions of virion protein 1 (VP1) of EV71. Furthermore, we observed that the inflammation caused by EV71 infection was restored to a moderate level via miR‐9 overexpression. Nuclear factor kappa B (NFκB) in the retinoic acid‐induced gene 1 (RIG‐I) signaling pathway, but not interferon regulating factor 3 (IRF3), was significantly decreased and inactivated by ectopic miR‐9 expression. Moreover, in mouse infection experiments, administration of miR‐9 agomirs caused a significant decrease in VP1 levels and pro‐inflammatory cytokine production after viral inoculation. Taken together, the present data demonstrate that miR‐9 exerts an anti‐EV71 effect in cells and a mouse model via mediating NFκB activity of the RIG‐I signal pathway, thereby suggesting a new candidate for antiviral drug development.",2018 Aug 29,"['Li, Bing', 'Zheng, Junqing']",FEBS Open Bio,,,True
c5b72b9084df4d6f9e471b0e320a6136a7db7f0c,PMC,Using DNA metabarcoding for simultaneous inference of common vampire bat diet and population structure,http://dx.doi.org/10.1111/1755-0998.12891,PMC6120510,29673092,CC BY,"Metabarcoding diet analysis has become a valuable tool in animal ecology; however, co‐amplified predator sequences are not generally used for anything other than to validate predator identity. Exemplified by the common vampire bat, we demonstrate the use of metabarcoding to infer predator population structure alongside diet assessments. Growing populations of common vampire bats impact human, livestock and wildlife health in Latin America through transmission of pathogens, such as lethal rabies viruses. Techniques to determine large‐scale variation in vampire bat diet and bat population structure would empower locality‐ and species‐specific projections of disease transmission risks. However, previously used methods are not cost‐effective and efficient for large‐scale applications. Using bloodmeal and faecal samples from common vampire bats from coastal, Andean and Amazonian regions of Peru, we showcase metabarcoding as a scalable tool to assess vampire bat population structure and feeding preferences. Dietary metabarcoding was highly effective, detecting vertebrate prey in 93.2% of the samples. Bats predominantly preyed on domestic animals, but fed on tapirs at one Amazonian site. In addition, we identified arthropods in 9.3% of samples, likely reflecting consumption of ectoparasites. Using the same data, we document mitochondrial geographic population structure in the common vampire bat in Peru. Such simultaneous inference of vampire bat diet and population structure can enable new insights into the interplay between vampire bat ecology and disease transmission risks. Importantly, the methodology can be incorporated into metabarcoding diet studies of other animals to couple information on diet and population structure.",2018 Sep 16,"['Bohmann, Kristine', 'Gopalakrishnan, Shyam', 'Nielsen, Martin', 'Nielsen, Luisa dos Santos Bay', 'Jones, Gareth', 'Streicker, Daniel G.', 'Gilbert, M. Thomas P.']",Mol Ecol Resour,,,True
f293ae4ed7e4a778e7f9cc024d4e4cb33d69cc6e,PMC,Using DNA metabarcoding for simultaneous inference of common vampire bat diet and population structure,http://dx.doi.org/10.1111/1755-0998.12891,PMC6120510,29673092,CC BY,"Metabarcoding diet analysis has become a valuable tool in animal ecology; however, co‐amplified predator sequences are not generally used for anything other than to validate predator identity. Exemplified by the common vampire bat, we demonstrate the use of metabarcoding to infer predator population structure alongside diet assessments. Growing populations of common vampire bats impact human, livestock and wildlife health in Latin America through transmission of pathogens, such as lethal rabies viruses. Techniques to determine large‐scale variation in vampire bat diet and bat population structure would empower locality‐ and species‐specific projections of disease transmission risks. However, previously used methods are not cost‐effective and efficient for large‐scale applications. Using bloodmeal and faecal samples from common vampire bats from coastal, Andean and Amazonian regions of Peru, we showcase metabarcoding as a scalable tool to assess vampire bat population structure and feeding preferences. Dietary metabarcoding was highly effective, detecting vertebrate prey in 93.2% of the samples. Bats predominantly preyed on domestic animals, but fed on tapirs at one Amazonian site. In addition, we identified arthropods in 9.3% of samples, likely reflecting consumption of ectoparasites. Using the same data, we document mitochondrial geographic population structure in the common vampire bat in Peru. Such simultaneous inference of vampire bat diet and population structure can enable new insights into the interplay between vampire bat ecology and disease transmission risks. Importantly, the methodology can be incorporated into metabarcoding diet studies of other animals to couple information on diet and population structure.",2018 Sep 16,"['Bohmann, Kristine', 'Gopalakrishnan, Shyam', 'Nielsen, Martin', 'Nielsen, Luisa dos Santos Bay', 'Jones, Gareth', 'Streicker, Daniel G.', 'Gilbert, M. Thomas P.']",Mol Ecol Resour,,,True
717582da95cea3e8b268b404e9f1ecc486fff6c1,PMC,"The Antiviral Effects of Na,K-ATPase Inhibition: A Minireview",http://dx.doi.org/10.3390/ijms19082154,PMC6121263,30042322,CC BY,"Since being first described more than 60 years ago, Na,K-ATPase has been extensively studied, while novel concepts about its structure, physiology, and biological roles continue to be elucidated. Cardiac glycosides not only inhibit the pump function of Na,K-ATPase but also activate intracellular signal transduction pathways, which are important in many biological processes. Recently, antiviral effects have been described as a novel feature of Na,K-ATPase inhibition with the use of cardiac glycosides. Cardiac glycosides have been reported to be effective against both DNA viruses such as cytomegalovirus and herpes simplex and RNA viruses such as influenza, chikungunya, coronavirus, and respiratory syncytial virus, among others. Consequently, cardiac glycosides have emerged as potential broad-spectrum antiviral drugs, with the great advantage of targeting cell host proteins, which help to minimize resistance to antiviral treatments, making them a very promising strategy against human viral infections. Here, we review the effect of cardiac glycosides on viral biology and the mechanisms by which these drugs impair the replication of this array of different viruses.",2018 Jul 24,"['Amarelle, Luciano', 'Lecuona, Emilia']",Int J Mol Sci,,,True
daf4eb5387fb452ec6b363fe7ed346df579535c1,PMC,Comparative Transcriptomic Analysis of Immune-Related Gene Expression in Duck Embryo Fibroblasts Following Duck Tembusu Virus Infection,http://dx.doi.org/10.3390/ijms19082328,PMC6121397,30096804,CC BY,"Duck is a major waterfowl species in China, providing high-economic benefit with a population of up to 20–30 billion per year. Ducks are commonly affected by severe diseases, including egg-drop syndrome caused by duck Tembusu virus (DTMUV). The immune mechanisms against DTMUV invasion and infection remain poorly understood. In this study, duck embryo fibroblasts (DEFs) were infected with DTMUV and harvested at 12 and 24 h post-infection (hpi), and their genomes were sequenced. In total, 911 (764 upregulated and 147 downregulated genes) and 3008 (1791 upregulated and 1217 downregulated) differentially expressed genes (DEGs) were identified at 12 and 24 hpi, respectively. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that DEGs were considerably enriched in immune-relevant pathways, including Toll-like receptor signaling pathway, Cytosolic DNA-sensing pathway, RIG-I-like receptor signaling pathway, Chemokine signaling pathway, NOD-like receptor signaling pathway, and Hematopoietic cell lineage at both time points. The key DEGs in immune system included those of the cytokines (IFN α2, IL-6, IL-8L, IL-12B, CCR7, CCL19, and CCL20), transcription factors or signaling molecules (IRF7, NF-κB, STAT1, TMEM173, and TNFAIP3), pattern recognition receptors (RIG-I and MDA5), and antigen-presenting proteins (CD44 and CD70). This suggests DTMUV infection induces strong proinflammatory/antiviral effects with enormous production of cytokines. However, these cytokines could not protect DEFs against viral attack. Our data revealed valuable transcriptional information regarding DTMUV-infected DEFs, thereby broadening our understanding of the immune response against DTMUV infection; this information might contribute in developing strategies for controlling the prevalence of DTMUV infection.",2018 Aug 8,"['Yu, Guanliu', 'Lin, Yun', 'Tang, Yi', 'Diao, Youxiang']",Int J Mol Sci,,,True
2c20b67e10309a26ad07fdb1ff5c86c9f966230a,PMC,Transmission of Influenza A in a Student Office Based on Realistic Person-to-Person Contact and Surface Touch Behaviour,http://dx.doi.org/10.3390/ijerph15081699,PMC6121424,30096894,CC BY,"Influenza A viruses result in the deaths of hundreds of thousands of individuals worldwide each year. In this study, influenza A transmission in a graduate student office is simulated via long-range airborne, fomite, and close contact routes based on real data from more than 3500 person-to-person contacts and 127,000 surface touches obtained by video-camera. The long-range airborne, fomite and close contact routes contribute to 54.3%, 4.2% and 44.5% of influenza A infections, respectively. For the fomite route, 59.8%, 38.1% and 2.1% of viruses are transmitted to the hands of students from private surfaces around the infected students, the students themselves and other susceptible students, respectively. The intranasal dose via fomites of the students’ bodies, belongings, computers, desks, chairs and public facilities are 8.0%, 6.8%, 13.2%, 57.8%, 9.3% and 4.9%, respectively. The intranasal dose does not monotonously increase or decrease with the virus transfer rate between hands and surfaces. Mask wearing is much more useful than hand washing for control of influenza A in the tested office setting. Regular cleaning of high-touch surfaces, which can reduce the infection risk by 2.14%, is recommended and is much more efficient than hand-washing.",2018 Aug 9,"['Zhang, Nan', 'Li, Yuguo']",Int J Environ Res Public Health,,,True
11eeefbcfc25ef1fb174852dba7dd71a12cb00fa,PMC,Transmission of Influenza A in a Student Office Based on Realistic Person-to-Person Contact and Surface Touch Behaviour,http://dx.doi.org/10.3390/ijerph15081699,PMC6121424,30096894,CC BY,"Influenza A viruses result in the deaths of hundreds of thousands of individuals worldwide each year. In this study, influenza A transmission in a graduate student office is simulated via long-range airborne, fomite, and close contact routes based on real data from more than 3500 person-to-person contacts and 127,000 surface touches obtained by video-camera. The long-range airborne, fomite and close contact routes contribute to 54.3%, 4.2% and 44.5% of influenza A infections, respectively. For the fomite route, 59.8%, 38.1% and 2.1% of viruses are transmitted to the hands of students from private surfaces around the infected students, the students themselves and other susceptible students, respectively. The intranasal dose via fomites of the students’ bodies, belongings, computers, desks, chairs and public facilities are 8.0%, 6.8%, 13.2%, 57.8%, 9.3% and 4.9%, respectively. The intranasal dose does not monotonously increase or decrease with the virus transfer rate between hands and surfaces. Mask wearing is much more useful than hand washing for control of influenza A in the tested office setting. Regular cleaning of high-touch surfaces, which can reduce the infection risk by 2.14%, is recommended and is much more efficient than hand-washing.",2018 Aug 9,"['Zhang, Nan', 'Li, Yuguo']",Int J Environ Res Public Health,,,False
767be20d25c46180b734e76c469b8f63cf9af3b3,PMC,Predicting Infectious Disease Using Deep Learning and Big Data,http://dx.doi.org/10.3390/ijerph15081596,PMC6121625,30060525,CC BY,"Infectious disease occurs when a person is infected by a pathogen from another person or an animal. It is a problem that causes harm at both individual and macro scales. The Korea Center for Disease Control (KCDC) operates a surveillance system to minimize infectious disease contagions. However, in this system, it is difficult to immediately act against infectious disease because of missing and delayed reports. Moreover, infectious disease trends are not known, which means prediction is not easy. This study predicts infectious diseases by optimizing the parameters of deep learning algorithms while considering big data including social media data. The performance of the deep neural network (DNN) and long-short term memory (LSTM) learning models were compared with the autoregressive integrated moving average (ARIMA) when predicting three infectious diseases one week into the future. The results show that the DNN and LSTM models perform better than ARIMA. When predicting chickenpox, the top-10 DNN and LSTM models improved average performance by 24% and 19%, respectively. The DNN model performed stably and the LSTM model was more accurate when infectious disease was spreading. We believe that this study’s models can help eliminate reporting delays in existing surveillance systems and, therefore, minimize costs to society.",2018 Aug 27,"['Chae, Sangwon', 'Kwon, Sungjun', 'Lee, Donghyun']",Int J Environ Res Public Health,,,True
a3086b69f66649e82594258fc55b8ca74032174e,PMC,Predicting Infectious Disease Using Deep Learning and Big Data,http://dx.doi.org/10.3390/ijerph15081596,PMC6121625,30060525,CC BY,"Infectious disease occurs when a person is infected by a pathogen from another person or an animal. It is a problem that causes harm at both individual and macro scales. The Korea Center for Disease Control (KCDC) operates a surveillance system to minimize infectious disease contagions. However, in this system, it is difficult to immediately act against infectious disease because of missing and delayed reports. Moreover, infectious disease trends are not known, which means prediction is not easy. This study predicts infectious diseases by optimizing the parameters of deep learning algorithms while considering big data including social media data. The performance of the deep neural network (DNN) and long-short term memory (LSTM) learning models were compared with the autoregressive integrated moving average (ARIMA) when predicting three infectious diseases one week into the future. The results show that the DNN and LSTM models perform better than ARIMA. When predicting chickenpox, the top-10 DNN and LSTM models improved average performance by 24% and 19%, respectively. The DNN model performed stably and the LSTM model was more accurate when infectious disease was spreading. We believe that this study’s models can help eliminate reporting delays in existing surveillance systems and, therefore, minimize costs to society.",2018 Aug 27,"['Chae, Sangwon', 'Kwon, Sungjun', 'Lee, Donghyun']",Int J Environ Res Public Health,,,False
1f8a1700ee536e43e65c9ba4df7f87b0461ee999,PMC,STAT3 in Skeletal Muscle Function and Disorders,http://dx.doi.org/10.3390/ijms19082265,PMC6121875,30072615,CC BY,"Signal transducer and activator of transcription 3 (STAT3) signaling plays critical roles in regulating skeletal muscle mass, repair, and diseases. In this review, we discuss the upstream activators of STAT3 in skeletal muscles, with a focus on interleukin 6 (IL6) and transforming growth factor beta 1 (TGF-β1). We will also discuss the double-edged effect of STAT3 activation in the muscles, including the role of STAT3 signaling in muscle hypertrophy induced by exercise training or muscle wasting in cachectic diseases and muscular dystrophies. STAT3 is a critical regulator of satellite cell self-renewal after muscle injury. STAT3 knock out affects satellite cell myogenic progression by impairing proliferation and inducing premature differentiation. Recent studies in STAT3 signaling demonstrated its direct role in controlling myogenic capacity of myoblasts and satellite cells, as well as the potential benefit in using STAT3 inhibitors to treat muscle diseases. However, prolonged STAT3 activation in muscles has been shown to be responsible for muscle wasting by activating protein degradation pathways. It is important to balance the extent of STAT3 activation and the duration and location (cell types) of the STAT3 signaling when developing therapeutic interventions. STAT3 signaling in other tissues and organs that can directly or indirectly affects skeletal muscle health are also discussed.",2018 Aug 2,"['Guadagnin, Eleonora', 'Mázala, Davi', 'Chen, Yi-Wen']",Int J Mol Sci,,,True
1b64cf541af6560335b092dc63f67dd4cd81691a,PMC,Impact of microbial Aetiology on mortality in severe community-acquired pneumonia,http://dx.doi.org/10.1186/s12879-018-3366-4,PMC6122562,30180811,CC BY,"BACKGROUND: The impact of different classes of microbial pathogens on mortality in severe community-acquired pneumonia is not well elucidated. Previous studies have shown significant variation in the incidence of viral, bacterial and mixed infections, with conflicting risk associations for mortality. We aimed to determine the risk association of microbial aetiologies with hospital mortality in severe CAP, utilising a diagnostic strategy incorporating molecular testing. Our primary hypothesis was that respiratory viruses were important causative pathogens in severe CAP and was associated with increased mortality when present with bacterial pathogens in mixed viral-bacterial co-infections. METHODS: A retrospective cohort study from January 2014 to July 2015 was conducted in a tertiary hospital medical intensive care unit in eastern Singapore, which has a tropical climate. All patients diagnosed with severe community-acquired pneumonia were included. RESULTS: A total of 117 patients were in the study. Microbial pathogens were identified in 84 (71.8%) patients. Mixed viral-bacterial co-infections occurred in 18 (15.4%) of patients. Isolated viral infections were present in 32 patients (27.4%); isolated bacterial infections were detected in 34 patients (29.1%). Hospital mortality occurred in 16 (13.7%) patients. The most common bacteria isolated was Streptococcus pneumoniae and the most common virus isolated was Influenza A. Univariate and multivariate logistic regression showed that serum procalcitonin, APACHE II severity score and mixed viral-bacterial infection were associated with increased risk of hospital mortality. Mixed viral-bacterial co-infections were associated with an adjusted odds ratio of 13.99 (95% CI 1.30–151.05, p = 0.03) for hospital mortality. CONCLUSIONS: Respiratory viruses are common organisms isolated in severe community-acquired pneumonia. Mixed viral-bacterial infections may be associated with an increased risk of mortality.",2018 Sep 4,"['Quah, Jessica', 'Jiang, Boran', 'Tan, Poh Choo', 'Siau, Chuin', 'Tan, Thean Yen']",BMC Infect Dis,,,True
0f76bdee678e512d5bfb2d3597ad57a1b5d74bc4,PMC,Spatiotemporal diffusion of influenza A (H1N1): Starting point and risk factors,http://dx.doi.org/10.1371/journal.pone.0202832,PMC6122785,30180215,CC BY,"Influenza constitutes a major challenge to world health authorities due to high transmissibility and the capacity to generate large epidemics. This study aimed to characterize the diffusion process of influenza A (H1N1) by identifying the starting point of the epidemic as well as climatic and sociodemographic factors associated with the occurrence and intensity of transmission of the disease. The study was carried out in the Brazilian state of Paraná, where H1N1 caused the largest impact. The units of spatial and temporal analysis were the municipality of residence of the cases and the epidemiological weeks of the year 2009, respectively. Under the Bayesian paradigm, parametric inference was performed through a two-part spatiotemporal model and the integrated nested Laplace approximation (INLA) algorithm. We identified the most likely starting points through the effective distance measure based on mobility networks. The proposed estimation methodology allowed for rapid and efficient implementation of the spatiotemporal model, and provided evidence of different patterns for chance of occurrence and risk of influenza throughout the epidemiological weeks. The results indicate the capital city of Curitiba as the probable starting point, and showed that the interventions that focus on municipalities with greater migration and density of people, especially those with higher Human Development Indexes (HDIs) and the presence of municipal air and road transport, could play an important role in mitigation of effects of future influenza pandemics on public health. These results provide important information on the process of introduction and spread of influenza, and could contribute to the identification of priority areas for surveillance as well as establishment of strategic measures for disease prevention and control. The proposed model also allows identification of epidemiological weeks with high chance of influenza occurrence, which can be used as a reference criterion for creating an immunization campaign schedule.",2018 Sep 4,"['da Costa, Ana Carolina Carioca', 'Codeço, Cláudia Torres', 'Krainski, Elias Teixeira', 'Gomes, Marcelo Ferreira da Costa', 'Nobre, Aline Araújo']",PLoS One,,,True
c49543f507a07bcef2a9568fa458fac552d51fcd,PMC,Novel coronavirus-like particles targeting cells lining the respiratory tract,http://dx.doi.org/10.1371/journal.pone.0203489,PMC6124810,30183777,CC BY,"Virus like particles (VLPs) produced by the expression of viral structural proteins can serve as versatile nanovectors or potential vaccine candidates. In this study we describe for the first time the generation of HCoV-NL63 VLPs using baculovirus system. Major structural proteins of HCoV-NL63 have been expressed in tagged or native form, and their assembly to form VLPs was evaluated. Additionally, a novel procedure for chromatography purification of HCoV-NL63 VLPs was developed. Interestingly, we show that these nanoparticles may deliver cargo and selectively transduce cells expressing the ACE2 protein such as ciliated cells of the respiratory tract. Production of a specific delivery vector is a major challenge for research concerning targeting molecules. The obtained results show that HCoV-NL63 VLPs may be efficiently produced, purified, modified and serve as a delivery platform. This study constitutes an important basis for further development of a promising viral vector displaying narrow tissue tropism.",2018 Sep 5,"['Naskalska, Antonina', 'Dabrowska, Agnieszka', 'Nowak, Paulina', 'Szczepanski, Artur', 'Jasik, Krzysztof', 'Milewska, Aleksandra', 'Ochman, Marek', 'Zeglen, Slawomir', 'Rajfur, Zenon', 'Pyrc, Krzysztof']",PLoS One,,,True
46411996e57929617bbb462c3cbc429d3e70619d,PMC,"An emerging novel goose astrovirus associated with gosling gout disease, China",http://dx.doi.org/10.1038/s41426-018-0153-7,PMC6125322,30185786,CC BY,"Since the first isolation from human, astroviruses have been detected in many species. Wide host range and occasional cross-transmission of astrovirus pose a risk for zoonotic infection. Here, novel astroviruses were identified from goslings with recent epidemic gout disease in China. A virus, designated as GD, was efficiently isolated from a diseased gosling using LMH cells. Genome of GD amplified using 5′ and 3′ RACE was 7183nt in full length. Sequence analysis revealed the genome of GD was <60.8% homology with others deposited in Genbank. Moreover, GD could be neutralized by goose convalescent sera, and the gout associated symptom in goslings could be reproduced by GD infection. Our data demonstrated the goose astrovirus could be one of the causative agents of the ongoing gosling gout disease in China. The identification of the goose astrovirus not only diversified the astrovirus species, but also broadened the disease patterns caused by astroviruses.",2018 Sep 5,"['Zhang, Xinyu', 'Ren, Dan', 'Li, Tuofan', 'Zhou, Huayan', 'Liu, Xiaoyu', 'Wang, Xiaobo', 'Lu, Hao', 'Gao, Wei', 'Wang, Yajuan', 'Zou, Xiaoyan', 'Sun, Huaichang', 'Ye, Jianqiang']",Emerg Microbes Infect,,,True
263a93d919f1c783a014ddb3f1b15d7ad3a3553b,PMC,SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death,http://dx.doi.org/10.1038/s41419-018-0917-y,PMC6125346,30185776,CC BY,"The molecular mechanisms underlying the severe lung pathology that occurs during SARS-CoV infections remain incompletely understood. The largest of the SARS-CoV accessory protein open reading frames (SARS 3a) oligomerizes, dynamically inserting into late endosomal, lysosomal, and trans-Golgi-network membranes. While previously implicated in a non-inflammatory apoptotic cell death pathway, here we extend the range of SARS 3a pathophysiologic targets by examining its effects on necrotic cell death pathways. We show that SARS 3a interacts with Receptor Interacting Protein 3 (Rip3), which augments the oligomerization of SARS 3a helping drive necrotic cell death. In addition, by inserting into lysosomal membranes SARS 3a triggers lysosomal damage and dysfunction. Consequently, Transcription Factor EB (TFEB) translocates to the nucleus increasing the transcription of autophagy- and lysosome-related genes. Finally, SARS 3a activates caspase-1 either directly or via an enhanced potassium efflux, which triggers NLRP3 inflammasome assembly. In summary, Rip3-mediated oligomerization of SARS 3a causes necrotic cell death, lysosomal damage, and caspase-1 activation—all likely contributing to the clinical manifestations of SARS-CoV infection.",2018 Sep 5,"['Yue, Yuan', 'Nabar, Neel R.', 'Shi, Chong-Shan', 'Kamenyeva, Olena', 'Xiao, Xun', 'Hwang, Il-Young', 'Wang, Min', 'Kehrl, John H.']",Cell Death Dis,,,True
7510fd5807ba58c1c3aee2def887c041331a4536,PMC,Crystal Dehydration in Membrane Protein Crystallography,http://dx.doi.org/10.1007/978-3-319-35072-1_6,PMC6126552,27553236,CC BY,"Crystal dehydration has been successfully implemented to facilitate the structural solution of a number of soluble and membrane protein structures over the years. This chapter will present the currently available tools to undertake controlled crystal dehydration, focusing on some successful membrane protein cases. Also discussed here will be some practical considerations regarding membrane protein crystals and the relationship between different techniques in order to help researchers to select the most suitable technique for their projects.",2016 Apr 28,"['Sanchez-Weatherby, Juan', 'Moraes, Isabel']",Adv Exp Med Biol,,,True
bc00727fee1ac89ccac1843a04427ff7a504be41,PMC,LY6E mediates an evolutionarily conserved enhancement of virus infection by targeting a late entry step,http://dx.doi.org/10.1038/s41467-018-06000-y,PMC6127192,30190477,CC BY,"Interferons (IFNs) contribute to cell-intrinsic antiviral immunity by inducing hundreds of interferon-stimulated genes (ISGs). In a screen to identify antiviral ISGs, we unexpectedly found that LY6E, a member of the LY6/uPAR family, enhanced viral infection. Here, we show that viral enhancement by ectopically expressed LY6E extends to several cellular backgrounds and affects multiple RNA viruses. LY6E does not impair IFN antiviral activity or signaling, but rather promotes viral entry. Using influenza A virus as a model, we narrow the enhancing effect of LY6E to uncoating after endosomal escape. Diverse mammalian orthologs of LY6E also enhance viral infectivity, indicating evolutionary conservation of function. By structure-function analyses, we identify a single amino acid in a predicted loop region that is essential for viral enhancement. Our study suggests that LY6E belongs to a class of IFN-inducible host factors that enhance viral infectivity without suppressing IFN antiviral activity.",2018 Sep 6,"['Mar, Katrina B.', 'Rinkenberger, Nicholas R.', 'Boys, Ian N.', 'Eitson, Jennifer L.', 'McDougal, Matthew B.', 'Richardson, R. Blake', 'Schoggins, John W.']",Nat Commun,,,True
8744fa6959106f1045dbffde97b64a6801c312b1,PMC,LY6E mediates an evolutionarily conserved enhancement of virus infection by targeting a late entry step,http://dx.doi.org/10.1038/s41467-018-06000-y,PMC6127192,30190477,CC BY,"Interferons (IFNs) contribute to cell-intrinsic antiviral immunity by inducing hundreds of interferon-stimulated genes (ISGs). In a screen to identify antiviral ISGs, we unexpectedly found that LY6E, a member of the LY6/uPAR family, enhanced viral infection. Here, we show that viral enhancement by ectopically expressed LY6E extends to several cellular backgrounds and affects multiple RNA viruses. LY6E does not impair IFN antiviral activity or signaling, but rather promotes viral entry. Using influenza A virus as a model, we narrow the enhancing effect of LY6E to uncoating after endosomal escape. Diverse mammalian orthologs of LY6E also enhance viral infectivity, indicating evolutionary conservation of function. By structure-function analyses, we identify a single amino acid in a predicted loop region that is essential for viral enhancement. Our study suggests that LY6E belongs to a class of IFN-inducible host factors that enhance viral infectivity without suppressing IFN antiviral activity.",2018 Sep 6,"['Mar, Katrina B.', 'Rinkenberger, Nicholas R.', 'Boys, Ian N.', 'Eitson, Jennifer L.', 'McDougal, Matthew B.', 'Richardson, R. Blake', 'Schoggins, John W.']",Nat Commun,,,False
9030e63a77c9fa25f099a8c8ea43d678f3693309,PMC,LY6E mediates an evolutionarily conserved enhancement of virus infection by targeting a late entry step,http://dx.doi.org/10.1038/s41467-018-06000-y,PMC6127192,30190477,CC BY,"Interferons (IFNs) contribute to cell-intrinsic antiviral immunity by inducing hundreds of interferon-stimulated genes (ISGs). In a screen to identify antiviral ISGs, we unexpectedly found that LY6E, a member of the LY6/uPAR family, enhanced viral infection. Here, we show that viral enhancement by ectopically expressed LY6E extends to several cellular backgrounds and affects multiple RNA viruses. LY6E does not impair IFN antiviral activity or signaling, but rather promotes viral entry. Using influenza A virus as a model, we narrow the enhancing effect of LY6E to uncoating after endosomal escape. Diverse mammalian orthologs of LY6E also enhance viral infectivity, indicating evolutionary conservation of function. By structure-function analyses, we identify a single amino acid in a predicted loop region that is essential for viral enhancement. Our study suggests that LY6E belongs to a class of IFN-inducible host factors that enhance viral infectivity without suppressing IFN antiviral activity.",2018 Sep 6,"['Mar, Katrina B.', 'Rinkenberger, Nicholas R.', 'Boys, Ian N.', 'Eitson, Jennifer L.', 'McDougal, Matthew B.', 'Richardson, R. Blake', 'Schoggins, John W.']",Nat Commun,,,True
885377ca4694790e9a7e390bcb546e62d1f2451f,PMC,"Viral communities associated with porcine respiratory disease complex in intensive commercial farms in Sichuan province, China",http://dx.doi.org/10.1038/s41598-018-31554-8,PMC6127300,30190594,CC BY,"Porcine respiratory disease complex (PRDC), a common piglet disease, causes substantive economic losses in pig farming. To investigate the viral diversity associated with PRDC, the viral communities in serum and nasal swabs from 26 PRDC-affected piglets were investigated using metagenomics. By deep sequencing and de novo assembly, 17 viruses were identified in two pooled libraries (16 viruses from serum, nine from nasal swabs). Porcine circovirus (PCV)-2, porcine reproductive and respiratory syndrome virus (PRRSV) and pseudorabies virus, all commonly associated with PRDC, were identified in the two pooled samples by metagenomics, but most viruses comprised small linear and circular DNAs (e.g. parvoviruses, bocaviruses and circoviruses). PCR was used to compare the detection rates of each virus in the serum samples from 36 PRDC-affected piglets versus 38 location-matched clinically healthy controls. The average virus category per sample was 6.81 for the PRDC-affected piglets and 4.09 for the controls. Single or co-infections with PCV-2 or PRRSV had very high detection rates in the PRDC-affected piglets. Interestingly, porcine parvovirus (PPV)-2, PPV-3, PPV-6 and torque teno sus virus 1a were significantly associated with PRDC. These results illustrate the complexity of viral communities in the PRDC-affected piglets and highlight the candidate viruses associated with it.",2018 Sep 6,"['Qin, Sinan', 'Ruan, Wenqiang', 'Yue, Hua', 'Tang, Cheng', 'Zhou, Kelei', 'Zhang, Bin']",Sci Rep,,,False
075fc26a9bf29767e3e3e29e22121ce3980fcbf2,PMC,"Viral communities associated with porcine respiratory disease complex in intensive commercial farms in Sichuan province, China",http://dx.doi.org/10.1038/s41598-018-31554-8,PMC6127300,30190594,CC BY,"Porcine respiratory disease complex (PRDC), a common piglet disease, causes substantive economic losses in pig farming. To investigate the viral diversity associated with PRDC, the viral communities in serum and nasal swabs from 26 PRDC-affected piglets were investigated using metagenomics. By deep sequencing and de novo assembly, 17 viruses were identified in two pooled libraries (16 viruses from serum, nine from nasal swabs). Porcine circovirus (PCV)-2, porcine reproductive and respiratory syndrome virus (PRRSV) and pseudorabies virus, all commonly associated with PRDC, were identified in the two pooled samples by metagenomics, but most viruses comprised small linear and circular DNAs (e.g. parvoviruses, bocaviruses and circoviruses). PCR was used to compare the detection rates of each virus in the serum samples from 36 PRDC-affected piglets versus 38 location-matched clinically healthy controls. The average virus category per sample was 6.81 for the PRDC-affected piglets and 4.09 for the controls. Single or co-infections with PCV-2 or PRRSV had very high detection rates in the PRDC-affected piglets. Interestingly, porcine parvovirus (PPV)-2, PPV-3, PPV-6 and torque teno sus virus 1a were significantly associated with PRDC. These results illustrate the complexity of viral communities in the PRDC-affected piglets and highlight the candidate viruses associated with it.",2018 Sep 6,"['Qin, Sinan', 'Ruan, Wenqiang', 'Yue, Hua', 'Tang, Cheng', 'Zhou, Kelei', 'Zhang, Bin']",Sci Rep,,,True
3268f252e2559df8ea83c97725a4412a003670ad,PMC,Polyanhydride Nanovaccine Induces Robust Pulmonary B and T Cell Immunity and Confers Protection Against Homologous and Heterologous Influenza A Virus Infections,http://dx.doi.org/10.3389/fimmu.2018.01953,PMC6127617,30233573,CC BY,"Influenza A virus (IAV) is a major cause of respiratory illness. Given the disease severity, associated economic costs, and recent appearance of novel IAV strains, there is a renewed interest in developing novel and efficacious “universal” IAV vaccination strategies. Recent studies have highlighted that immunizations capable of generating local (i.e., nasal mucosa and lung) tissue-resident memory T and B cells in addition to systemic immunity offer the greatest protection against future IAV encounters. Current IAV vaccines are designed to largely stimulate IAV-specific antibodies, but do not generate the lung-resident memory T and B cells induced during IAV infections. Herein, we report on an intranasally administered biocompatible polyanhydride nanoparticle-based IAV vaccine (IAV-nanovax) capable of providing protection against subsequent homologous and heterologous IAV infections in both inbred and outbred populations. Our findings also demonstrate that vaccination with IAV-nanovax promotes the induction of germinal center B cells within the lungs, both systemic and lung local IAV-specific antibodies, and IAV-specific lung-resident memory CD4 and CD8 T cells. Altogether our findings show that an intranasally administered nanovaccine can induce immunity within the lungs, similar to what occurs during IAV infections, and thus could prove useful as a strategy for providing “universal” protection against IAV.",2018 Aug 28,"['Zacharias, Zeb R.', 'Ross, Kathleen A.', 'Hornick, Emma E.', 'Goodman, Jonathan T.', 'Narasimhan, Balaji', 'Waldschmidt, Thomas J.', 'Legge, Kevin L.']",Front Immunol,,,True
3fe826257f69f938e7b828852a602a453c09c89b,PMC,"Canine morbillivirus (canine distemper virus) with concomitant canine adenovirus, canine parvovirus-2, and Neospora caninum in puppies: a retrospective immunohistochemical study",http://dx.doi.org/10.1038/s41598-018-31540-0,PMC6128882,30194440,CC BY,"A retrospective immunohistochemical study was designed to investigate the frequency of concomitant traditional infectious disease pathogens in puppies that died suddenly and review the aspects of associated pathogenesis. Fifteen puppies were evaluated; the pathology reports and histopathologic slides of these animals were reviewed to determine the pattern of histopathologic lesions. The intralesional identification of antigens of canine (distemper) morbillivirus (CDV), canine adenovirus-1 and -2 (CAdV-1 and -2), canine parvovirus-2 (CPV-2), Toxoplasma gondii, and Neospora caninum was evaluated by IHC within the histopathologic patterns observed. All puppies contained CDV nucleic acid by molecular testing. The most frequent histopathologic patterns were intestinal crypt necrosis (n = 8), white matter cerebellar demyelination (n = 7), necrohaemorrhagic hepatitis (n = 7), interstitial pneumonia (n = 7), and gallbladder oedema (n = 5). All puppies contained intralesional antigens of CDV in multiple tissues resulting in singular (n = 3), and concomitant dual (n = 3), triple (n = 5) and quadruple (n = 4) infections by CAdV-1, and -2, CPV-2, and N. caninum; T. gondii was not identified. Concomitant infections by CDV was observed with N. caninum (100%; 1/1), CPV-2 (100%; 8/8), CAdV-1 (100%; 8/8), and CAdV-2 (100%; 8/8). Intralesional antigens of CDV and not CAdV-1 were identified in cases of gallbladder oedema. The “blue eye” phenomenon was histologically characterized by corneal oedema and degenerative lesions to the corneal epithelium, without inflammatory reactions.",2018 Sep 7,"['Headley, Selwyn A.', 'Oliveira, Thalita E. S.', 'Pereira, Alfredo H. T.', 'Moreira, Jéssica R.', 'Michelazzo, Mariana M. Z.', 'Pires, Bárbara G.', 'Marutani, Victor Hugo B.', 'Xavier, Ana A. C.', 'Di Santis, Giovana W.', 'Garcia, João L.', 'Alfieri, Amauri A.']",Sci Rep,,,False
e0bf08186f4d0b6112d6f4b8535584739da35596,PMC,"Canine morbillivirus (canine distemper virus) with concomitant canine adenovirus, canine parvovirus-2, and Neospora caninum in puppies: a retrospective immunohistochemical study",http://dx.doi.org/10.1038/s41598-018-31540-0,PMC6128882,30194440,CC BY,"A retrospective immunohistochemical study was designed to investigate the frequency of concomitant traditional infectious disease pathogens in puppies that died suddenly and review the aspects of associated pathogenesis. Fifteen puppies were evaluated; the pathology reports and histopathologic slides of these animals were reviewed to determine the pattern of histopathologic lesions. The intralesional identification of antigens of canine (distemper) morbillivirus (CDV), canine adenovirus-1 and -2 (CAdV-1 and -2), canine parvovirus-2 (CPV-2), Toxoplasma gondii, and Neospora caninum was evaluated by IHC within the histopathologic patterns observed. All puppies contained CDV nucleic acid by molecular testing. The most frequent histopathologic patterns were intestinal crypt necrosis (n = 8), white matter cerebellar demyelination (n = 7), necrohaemorrhagic hepatitis (n = 7), interstitial pneumonia (n = 7), and gallbladder oedema (n = 5). All puppies contained intralesional antigens of CDV in multiple tissues resulting in singular (n = 3), and concomitant dual (n = 3), triple (n = 5) and quadruple (n = 4) infections by CAdV-1, and -2, CPV-2, and N. caninum; T. gondii was not identified. Concomitant infections by CDV was observed with N. caninum (100%; 1/1), CPV-2 (100%; 8/8), CAdV-1 (100%; 8/8), and CAdV-2 (100%; 8/8). Intralesional antigens of CDV and not CAdV-1 were identified in cases of gallbladder oedema. The “blue eye” phenomenon was histologically characterized by corneal oedema and degenerative lesions to the corneal epithelium, without inflammatory reactions.",2018 Sep 7,"['Headley, Selwyn A.', 'Oliveira, Thalita E. S.', 'Pereira, Alfredo H. T.', 'Moreira, Jéssica R.', 'Michelazzo, Mariana M. Z.', 'Pires, Bárbara G.', 'Marutani, Victor Hugo B.', 'Xavier, Ana A. C.', 'Di Santis, Giovana W.', 'Garcia, João L.', 'Alfieri, Amauri A.']",Sci Rep,,,True
638ee8a365b38f69e411c8d92bb90c2b6c4fb405,PMC,An original design of remote robot-assisted intubation system,http://dx.doi.org/10.1038/s41598-018-31607-y,PMC6128927,30194353,CC BY,"The success rate of pre-hospital endotracheal intubation (ETI) by paramedics is lower than physicians. We aimed to establish a remote robot-assisted intubation system (RRAIS) and expected it to improve success rate of pre-hospital ETI. To test the robot’s feasibility, 20 pigs were intubated by direct laryngoscope or the robot system. Intubation time, success rate, airway complications were recorded during the experiment. The animal experiment showed that participants achieved a higher success rate in absolute numbers by the robot system. In summary, we have successfully developed a remote robot-assisted intubation system. It is promising for RRAIS to improve the success rate of pre-hospital ETI and change the current rescue model.",2018 Sep 7,"['Wang, Xinyu', 'Tao, Yuanfa', 'Tao, Xiandong', 'Chen, Jianglong', 'Jin, Yifeng', 'Shan, Zhengxiang', 'Tan, Jiyang', 'Cao, Qixin', 'Pan, Tiewen']",Sci Rep,,,True
cb57d1d9d929477c14cabe401b967245c70b4715,PMC,Crystal structure of the post-fusion core of the Human coronavirus 229E spike protein at 1.86 Å resolution,http://dx.doi.org/10.1107/S2059798318008318,PMC6130466,30198895,CC BY,"Human coronavirus 229E (HCoV-229E) usually causes mild upper respiratory infections in heathy adults, but may lead to severe complications or mortality in individuals with weakened immune systems. Virus entry of HCoV-229E is mediated by its spike (S) protein, where the S1 domain facilitates attachment to host cells and the S2 domain is involved in subsequent fusion of the virus and host membranes. During the fusion process, two heptad repeats, HR1 and HR2, in the S2 domain assemble into a six-helix membrane-fusion structure termed the fusion core. Here, the complete fusion-core structure of HCoV-229E has been determined at 1.86 Å resolution, representing the most complete post-fusion conformation thus far among published human alphacoronavirus (α-HCoV) fusion-core structures. The overall structure of the HCoV-229E fusion core is similar to those of SARS, MERS and HCoV-NL63, but the packing of its 3HR1 core differs from those of SARS and MERS in that it contains more noncanonical ‘x’ and ‘da’ layers. Side-by-side electrostatic surface comparisons reveal that the electrostatic surface potentials are opposite in α-HCoVs and β-HCoVs at certain positions and that the HCoV-229E surface also appears to be the most hydrophobic among the various HCoVs. In addition to the highly conserved hydrophobic interactions between HR1 and HR2, some polar and electrostatic interactions are also well preserved across different HCoVs. This study adds to the structural profiling of HCoVs to aid in the structure-based design of pan-coronavirus small molecules or peptides to inhibit viral fusion.",2018 Sep 3,"['Yan, Lei', 'Meng, Bing', 'Xiang, Jiangchao', 'Wilson, Ian A.', 'Yang, Bei']",Acta Crystallogr D Struct Biol,,,True
6dc7f0acaa45433001b3b0586094e88c0d400911,PMC,"Quantitative analysis of rutin, quercetin, naringenin, and gallic acid by validated RP- and NP-HPTLC methods for quality control of anti-HBV active extract of Guiera senegalensis",http://dx.doi.org/10.1080/13880209.2017.1300175,PMC6130481,28283004,CC BY,"Context:Guiera senegalensis J.F. Gmel (Combretaceae) is a folk medicinal plant used in various metabolic and infectious diseases. In addition to its antiviral activities against herpes and fowlpox, the anti-HBV efficacy is very recently reported. Objective: To develop and validate simple, sensitive RP-/NP-HPTLC methods for quantitative determination of biomarkers rutin, quercetin, naringenin, and gallic acid in the anti-HBV active G. senegalensis leaves ethanol-extract. Materials and methods: RP-HPTLC (rutin & quercetin; phase- acetonitrile:water, 4:6) and NP-HPTLC (naringenin & gallic acid; phase- toluene:ethyl acetate:formic acid, 6:4:0.8) were performed on glass-backed silica gel plates 60F(254)-RP18 and 60F(254), respectively. The methods were validated according to the ICH guidelines. Results: Well-separated and compact spots (R(f)) of rutin (0.52 ± 0.006), quercetin (0.23 ± 0.005), naringenin (0.56 ± 0.009) and gallic acid (0.28 ± 0.006) were detected. The regression equations (Y) were 12.434x + 443.49, 10.08x + 216.85, 11.253x + 973.52 and 11.082x + 446.41 whereas the coefficient correlations (r(2)) were 0.997 ± 0.0004, 0.9982 ± 0.0001, 0.9974 ± 0.0004 and 0.9981 ± 0.0001, respectively. The linearity ranges (ng/spot) were 200–1400 (RP-HPTLC) and 100–1200 (NP-HPTLC). The LOD/LOQ (ng/band) were 33.03/100.1 (rutin), 9.67/29.31 (quercetin), 35.574/107.8 (naringenin), and 12.32/37.35 (gallic acid). Gallic acid (7.01 μg/mg) was the most abundant biomarker compared to rutin (2.42 μg/mg), quercetin (1.53 μg/mg) and naringenin (0.14 μg/mg) in the extract. Conclusion: The validated NP-/RP-HPTLC methods were simple, accurate, and sensitive for separating and quantifying antiviral biomarkers in G. senegalensis, and endorsed its anti-HBV activity. The developed methods could be further employed in the standardization and quality-control of herbal formulations.",2017 Mar 10,"['Alam, Perwez', 'Parvez, Mohammad K.', 'Arbab, Ahmed H.', 'Al-Dosari, Mohammed S.']",Pharm Biol,,,True
7b0510f8258fc50bcff6f0e1a66c54c04093f9d1,PMC,A systematic review of the active saikosaponins and extracts isolated from Radix Bupleuri and their applications,http://dx.doi.org/10.1080/13880209.2016.1262433,PMC6130612,27951737,CC BY,"Context: Radix Bupleuri has been used in traditional Chinese medicine for over 2000 years with functions of relieving exterior syndrome, clearing heat, regulating liver-qi, and lifting yang-qi. More natural active compounds, especially saikosaponins, have been isolated from Radix Bupleuri, which possess various valuable pharmacological activities. Objective: To summarize the current knowledge on pharmacological activities, mechanisms and applications of extracts and saikosaponins isolated from Radix Bupleuri, and obtain new insights for further research and development of Radix Bupleuri. Methods: PubMed, Web of Science, Science Direct, Research Gate, Academic Journals and Google Scholar were used as information sources through the inclusion of the search terms ‘Radix Bupleuri’, ‘Bupleurum’, ‘saikosaponins’, ‘Radix Bupleuri preparation’, and their combinations, mainly from the year 2008 to 2016 without language restriction. Clinical preparations containing Radix Bupleuri were collected from official website of China Food and Drug Administration (CFDA). Results and conclusion: 296 papers were searched and 128 papers were reviewed. A broad spectrum of in vitro and in vivo research has proved that Radix Bupleuri extracts, saikosaponin a, saikosaponin d, saikosaponin c, and saikosaponin b(2), exhibit evident anti-inflammatory, antitumor, antiviral, anti-allergic, immunoregulation, and neuroregulation activities mainly through NF-κB, MAPK or other pathways. 15 clinical preparations approved by CFDA remarkably broaden the application of Radix Bupleuri. The main side effect of Radix Bupleuri is liver damage when the dosage is excess, which indicates that the maximum tolerated dose is critical for clinical use of Radix Bupleuri extract and purified compounds.",2016 Dec 12,"['Yuan, Bochuan', 'Yang, Rui', 'Ma, Yongsheng', 'Zhou, Shan', 'Zhang, Xiaodong', 'Liu, Ying']",Pharm Biol,,,True
6a2d0c94c7467bc93eab84eb348c458e85738aa3,PMC,Anti-inflammatory effect of torilidis fructus ethanol extract through inhibition of Src,http://dx.doi.org/10.1080/13880209.2017.1362011,PMC6130681,28832235,CC BY,"Context: Torilidis fructus, fruits of Torilis japonica Decadolle (Umbelliferae), is a medicinal herb traditionally used as a pesticide, an astrictive, or a medicine for various inflammatory diseases. Objectives: Due to the lack of pharmacological studies on this herbal medicine, we explored the inhibitory activity of torilidis fructus on the macrophage-mediated inflammatory response using its ethanol extract (Tf-EE). Material and methods: The Griess assay and prostaglandin (PGE(2)) ELISA assay were conducted with Tf-EE (0-75 µg/mL) and LPS (1 µg/mL) treated RAW264.7 cells in cultured media. Tf-EE pretreated RAW264.7 cells were incubated with LPS for 6 h and semi-quantitative PCR was performed. Reporter gene assays, overexpression of target enzymes and immunoblotting were performed on macrophages to determine the molecular targets of Tf-EE. Results: Tf-EE markedly suppressed the inflammatory response of macrophages, such as lipopolysaccharide (LPS)-induced nitric oxide (NO) and PGE(2) production with IC(50) values of 35.66 and 62.47 µg/mL, respectively. It was also found that Tf-EE reduced the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 by 80%. Nuclear translocation and activation of nuclear factor (NF)-κB (p65 and p50) were declined by 60% and 30% respectively, and their regulatory events including the phosphorylation of AKT, IκBα, Src, and the formation of complexes between Src and p-p85 were also recognized to be diminished. Conclusions: The signalling events managed by Src and p85 complex seemed to be critically involved in Tf-EE-mediated anti-inflammatory response. This might suggest that Tf-EE exhibited anti-inflammatory effects through Src-targeted inhibition of NF-κB.",2017 Aug 23,"['Park, Gyubyung', 'Kim, Eunji', 'Son, Young-Jin', 'Yoon, Deok Hyo', 'Sung, Gi-Ho', 'Aravinthan, Adithan', 'Park, Yung Chul', 'Kim, Jong-Hoon', 'Cho, Jae Youl']",Pharm Biol,,,True
d8f8b6d50f16dfbdf817c36004a0424d44f35e93,PMC,Characterization of the hypersensitive response‐like cell death phenomenon induced by targeting antiviral lectin griffithsin to the secretory pathway,http://dx.doi.org/10.1111/pbi.12917,PMC6131415,29509998,CC BY,"Griffithsin (GRFT) is an antiviral lectin, originally derived from a red alga, which is currently being investigated as a topical microbicide to prevent transmission of human immunodeficiency virus (HIV). Targeting GRFT to the apoplast for production in Nicotiana benthamiana resulted in necrotic symptoms associated with a hypersensitive response (HR)‐like cell death, accompanied by H(2)O(2) generation and increased PR1 expression. Mannose‐binding lectins surfactant protein D (SP‐D), cyanovirin‐N (CV‐N) and human mannose‐binding lectin (hMBL) also induce salicylic acid (SA)‐dependent HR‐like cell death in N. benthamiana, and this effect is mediated by the lectin's glycan binding activity. We found that secreted GRFT interacts with an endogenous glycoprotein, α‐xylosidase (XYL1), which is involved in cell wall organization. The necrotic effect could be mitigated by overexpression of Arabidopsis XYL1, and by co‐expression of SA‐degrading enzyme NahG, providing strategies for enhancing expression of oligomannose‐binding lectins in plants.",2018 Oct 2,"['Kim, Bo Min', 'Lotter‐Stark, Hester Catharina Therese', 'Rybicki, Edward P.', 'Chikwamba, Rachel K.', 'Palmer, Kenneth E.']",Plant Biotechnol J,,,True
2d874577cfbe77f483ae4988cda1975f8d470c91,PMC,The human microglial HMC3 cell line: where do we stand? A systematic literature review,http://dx.doi.org/10.1186/s12974-018-1288-0,PMC6131758,30200996,CC BY,"Microglia, unique myeloid cells residing in the brain parenchyma, represent the first line of immune defense within the central nervous system. In addition to their immune functions, microglial cells play an important role in other cerebral processes, including the regulation of synaptic architecture and neurogenesis. Chronic microglial activation is regarded as detrimental, and it is considered a pathogenic mechanism common to several neurological disorders. Microglial activation and function have been extensively studied in rodent experimental models, whereas the characterization of human cells has been limited due to the restricted availability of primary sources of human microglia. To overcome this problem, human immortalized microglial cell lines have been developed. The human microglial clone 3 cell line, HMC3, was established in 1995, through SV40-dependent immortalization of human embryonic microglial cells. It has been recently authenticated by the American Type Culture Collection (ATCC®) and distributed under the name of HMC3 (ATCC®CRL-3304). The HMC3 cells have been used in six research studies, two of which also indicated by ATCC® as reference articles. However, a more accurate literature revision suggests that clone 3 was initially distributed under the name of CHME3. In this regard, several studies have been published, thus contributing to a more extensive characterization of this cell line. Remarkably, the same cell line has been used in different laboratories with other denominations, i.e., CHME-5 cells and C13-NJ cells. In view of the fact that “being now authenticated by ATCC®” may imply a wider distribution of the cells, we aimed at reviewing data obtained with the human microglia cell line clone 3, making the readers aware of this complicated nomenclature. In addition, we also included original data, generated in our laboratory with the HMC3 (ATCC®CRL-3304) cells, providing information on the current state of the culture together with supplementary details on the culturing procedures to obtain and maintain viable cells.",2018 Sep 10,"['Dello Russo, Cinzia', 'Cappoli, Natalia', 'Coletta, Isabella', 'Mezzogori, Daniele', 'Paciello, Fabiola', 'Pozzoli, Giacomo', 'Navarra, Pierluigi', 'Battaglia, Alessandra']",J Neuroinflammation,,,True
13a2da5074d1480d1e302628606afd1f17ac782e,PMC,Upper respiratory infections in a rural area with reduced malaria transmission in Senegal: a pathogens community study,http://dx.doi.org/10.1186/s12879-018-3362-8,PMC6131886,30200897,CC BY,"BACKGROUND: Acute Respiratory Infections (ARI) are common causes of febrile illnesses in many settings in Senegal. These infections are usually managed presumptively due to lack of appropriate diagnostic tools. This situation, can lead to poor management of febrile illness or antibiotic misuse. In addition, there are limited data on the spectrum of pathogens commonly responsible for these ARI. This study was conducted to explore the pathogens community among patients with acute respiratory infection in a rural area in Senegal. METHODS: A cross sectional study was conducted from August to December 2015. Children and adult patients attending Keur Socé health post for signs suggestive of acute respiratory infection were enrolled after providing inform consent. Eligible participants were recruited using a consecutive sampling method. Paired nose and throat swabs were collected for pathogen detection. Samples were processed using a multiplex PCR designed to identify 21 pathogens including both virus and bacteria. RESULTS: Two hundred and fifty patients participated in the study. Samples positivity rate was evaluated at 95.2% (238/250). Streptococcus pneumoniae was the predominant pathogen (74%) and was present in all months and all age-groups, followed by Staphylococcus aureus (28,8%) and rhinovirus (28,4%). Respiratory syncytial virus (RSV) was detected only among children under 5 years old in August and September while coronavirus was present in all age groups, during the months of October and December. CONCLUSION: This pilot study revealed a diversity of pathogens over the time and across all age groups, highlighting the need for further exploration. A pathogen community approach including both virus and bacteria at a larger scale becomes crucial for a better understanding of transmission dynamics at population level in order to help shape ARI control strategies.",2018 Sep 10,"['Tine, Roger C.', 'Ndiaye, Léon A.', 'Niang, Mbayame N.', 'Kiori, Davy E.', 'Dia, Ndongo', 'Gaye, Oumar', 'Broutin, Hélène']",BMC Infect Dis,,,True
eb65ef8d3ff24ddb51c4f091a46394f513a9d4d9,PMC,Intracranial Inoculation Is More Potent Than Intranasal Inoculation for Inducing Optic Neuritis in the Mouse Hepatitis Virus-Induced Model of Multiple Sclerosis,http://dx.doi.org/10.3389/fcimb.2018.00311,PMC6132074,30234031,CC BY,"Neurotropic strains of mouse hepatitis virus (MHV) induce acute inflammation and chronic demyelination in the spinal cord and optic nerves mediated by axonal spread following intracranial inoculation in mice, with pathologic features similar to the human demyelinating disease multiple sclerosis. Spinal cord demyelination is also induced following intranasal inoculation with neurotropic MHV strains, however much higher viral doses are required as compared to intracranial inoculation. Recently, it was shown that intranasal administration of low concentrations of proteins leads to significant, rapid accumulation of protein in the optic nerve and in the eye, with only low levels reaching spinal cord and other brain regions. Thus, we examined whether intranasal inoculation with MHV at doses equivalent to those given intracranially could induce optic neuritis—inflammation, demyelination and loss of retinal ganglion cells (RGCs) in the optic nerve with or without inducing spinal cord demyelination. Four week old male C57BL/6J mice were inoculated intracranially with the recombinant demyelinating strain RSA59, or intranasally with RSA59 or the non-demyelinating strain RSMHV2 as control. One month post-inoculation, mice inoculated intracranially with RSA59 had significant myelin loss in both spinal cord and optic nerves, with significant loss of RGCs as well, consistent with prior studies. As expected, intranasal inoculation with RSA59 failed to induce demyelination in spinal cord; however, it also did not induce optic nerve demyelination. No acute inflammation was found, and no viral antigen was detected, in the optic nerve or retina 1 day after inoculation. Results confirm the neurotropic effects of RSA59 following intracranial inoculation, and suggest that direct infection with axonal transport of virus from brain to spinal cord and optic nerve is required to induce demyelinating disease. These studies suggest that MHV does not selectively concentrate in optic nerve and retina to sufficient levels to induce demyelination following intranasal inoculation. Intracranial inoculation should continue to be considered a preferred method for studies of MHV-induced optic neuritis and central nervous system (CNS) demyelinating disease.",2018 Sep 4,"['Singh, Manmeet', 'Khan, Reas S.', 'Dine, Kimberly', 'Das Sarma, Jayasri', 'Shindler, Kenneth S.']",Front Cell Infect Microbiol,,,True
eaecf63c626997baa80666fd6a9a7714f3ac8dc2,PMC,Of mice and men: the host response to influenza virus infection,http://dx.doi.org/10.1007/s00335-018-9750-y,PMC6132725,29947965,CC BY,"Influenza virus (IV) infections represent a very serious public health problem. At present, no established biomarkers exist to support diagnosis for respiratory viral infections and more importantly for severe IV disease. Studies in animal models are extremely important to understand the biological, genetic, and environmental factors that contribute to severe IV disease and to validate biomarker candidates from human studies. However, mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs, whereas in humans almost all studies use peripheral blood from patients. In addition, human studies do not consider genetic background as variable although human populations are genetically very diverse. Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection. Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans. The top-regulated genes in humans were also differentially regulated in mice. We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans. Furthermore, mouse studies allow confirmation of findings in humans in a well-controlled experimental system adding enormous value to the understanding of expression and function of human candidate genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00335-018-9750-y) contains supplementary material, which is available to authorized users.",2018 Jun 15,"['Kollmus, Heike', 'Pilzner, Carolin', 'Leist, Sarah R.', 'Heise, Mark', 'Geffers, Robert', 'Schughart, Klaus']",Mamm Genome,,,False
544a01733887bc2d1363ab26b4b40c47ed903ff6,PMC,Of mice and men: the host response to influenza virus infection,http://dx.doi.org/10.1007/s00335-018-9750-y,PMC6132725,29947965,CC BY,"Influenza virus (IV) infections represent a very serious public health problem. At present, no established biomarkers exist to support diagnosis for respiratory viral infections and more importantly for severe IV disease. Studies in animal models are extremely important to understand the biological, genetic, and environmental factors that contribute to severe IV disease and to validate biomarker candidates from human studies. However, mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs, whereas in humans almost all studies use peripheral blood from patients. In addition, human studies do not consider genetic background as variable although human populations are genetically very diverse. Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection. Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans. The top-regulated genes in humans were also differentially regulated in mice. We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans. Furthermore, mouse studies allow confirmation of findings in humans in a well-controlled experimental system adding enormous value to the understanding of expression and function of human candidate genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00335-018-9750-y) contains supplementary material, which is available to authorized users.",2018 Jun 15,"['Kollmus, Heike', 'Pilzner, Carolin', 'Leist, Sarah R.', 'Heise, Mark', 'Geffers, Robert', 'Schughart, Klaus']",Mamm Genome,,,False
d6398e61198491bab8f107952efe2bc30b9260b2,PMC,Of mice and men: the host response to influenza virus infection,http://dx.doi.org/10.1007/s00335-018-9750-y,PMC6132725,29947965,CC BY,"Influenza virus (IV) infections represent a very serious public health problem. At present, no established biomarkers exist to support diagnosis for respiratory viral infections and more importantly for severe IV disease. Studies in animal models are extremely important to understand the biological, genetic, and environmental factors that contribute to severe IV disease and to validate biomarker candidates from human studies. However, mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs, whereas in humans almost all studies use peripheral blood from patients. In addition, human studies do not consider genetic background as variable although human populations are genetically very diverse. Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection. Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans. The top-regulated genes in humans were also differentially regulated in mice. We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans. Furthermore, mouse studies allow confirmation of findings in humans in a well-controlled experimental system adding enormous value to the understanding of expression and function of human candidate genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00335-018-9750-y) contains supplementary material, which is available to authorized users.",2018 Jun 15,"['Kollmus, Heike', 'Pilzner, Carolin', 'Leist, Sarah R.', 'Heise, Mark', 'Geffers, Robert', 'Schughart, Klaus']",Mamm Genome,,,True
6e6c7a4e78fe8ffc7ca59f523fd6fcdef4333758,PMC,Of mice and men: the host response to influenza virus infection,http://dx.doi.org/10.1007/s00335-018-9750-y,PMC6132725,29947965,CC BY,"Influenza virus (IV) infections represent a very serious public health problem. At present, no established biomarkers exist to support diagnosis for respiratory viral infections and more importantly for severe IV disease. Studies in animal models are extremely important to understand the biological, genetic, and environmental factors that contribute to severe IV disease and to validate biomarker candidates from human studies. However, mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs, whereas in humans almost all studies use peripheral blood from patients. In addition, human studies do not consider genetic background as variable although human populations are genetically very diverse. Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection. Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans. The top-regulated genes in humans were also differentially regulated in mice. We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans. Furthermore, mouse studies allow confirmation of findings in humans in a well-controlled experimental system adding enormous value to the understanding of expression and function of human candidate genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00335-018-9750-y) contains supplementary material, which is available to authorized users.",2018 Jun 15,"['Kollmus, Heike', 'Pilzner, Carolin', 'Leist, Sarah R.', 'Heise, Mark', 'Geffers, Robert', 'Schughart, Klaus']",Mamm Genome,,,True
646b9174e7fbba65d545caf0347e94f6d63e7ad3,PMC,Of mice and men: the host response to influenza virus infection,http://dx.doi.org/10.1007/s00335-018-9750-y,PMC6132725,29947965,CC BY,"Influenza virus (IV) infections represent a very serious public health problem. At present, no established biomarkers exist to support diagnosis for respiratory viral infections and more importantly for severe IV disease. Studies in animal models are extremely important to understand the biological, genetic, and environmental factors that contribute to severe IV disease and to validate biomarker candidates from human studies. However, mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs, whereas in humans almost all studies use peripheral blood from patients. In addition, human studies do not consider genetic background as variable although human populations are genetically very diverse. Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection. Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans. The top-regulated genes in humans were also differentially regulated in mice. We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans. Furthermore, mouse studies allow confirmation of findings in humans in a well-controlled experimental system adding enormous value to the understanding of expression and function of human candidate genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00335-018-9750-y) contains supplementary material, which is available to authorized users.",2018 Jun 15,"['Kollmus, Heike', 'Pilzner, Carolin', 'Leist, Sarah R.', 'Heise, Mark', 'Geffers, Robert', 'Schughart, Klaus']",Mamm Genome,,,True
3d4bcf09bf7e247b4f3f93954b3bf07a14375c4d,PMC,Of mice and men: the host response to influenza virus infection,http://dx.doi.org/10.1007/s00335-018-9750-y,PMC6132725,29947965,CC BY,"Influenza virus (IV) infections represent a very serious public health problem. At present, no established biomarkers exist to support diagnosis for respiratory viral infections and more importantly for severe IV disease. Studies in animal models are extremely important to understand the biological, genetic, and environmental factors that contribute to severe IV disease and to validate biomarker candidates from human studies. However, mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs, whereas in humans almost all studies use peripheral blood from patients. In addition, human studies do not consider genetic background as variable although human populations are genetically very diverse. Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection. Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans. The top-regulated genes in humans were also differentially regulated in mice. We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans. Furthermore, mouse studies allow confirmation of findings in humans in a well-controlled experimental system adding enormous value to the understanding of expression and function of human candidate genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00335-018-9750-y) contains supplementary material, which is available to authorized users.",2018 Jun 15,"['Kollmus, Heike', 'Pilzner, Carolin', 'Leist, Sarah R.', 'Heise, Mark', 'Geffers, Robert', 'Schughart, Klaus']",Mamm Genome,,,False
38e3755a70fbb6d1438f284fe4263a54b060e4f9,PMC,Of mice and men: the host response to influenza virus infection,http://dx.doi.org/10.1007/s00335-018-9750-y,PMC6132725,29947965,CC BY,"Influenza virus (IV) infections represent a very serious public health problem. At present, no established biomarkers exist to support diagnosis for respiratory viral infections and more importantly for severe IV disease. Studies in animal models are extremely important to understand the biological, genetic, and environmental factors that contribute to severe IV disease and to validate biomarker candidates from human studies. However, mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs, whereas in humans almost all studies use peripheral blood from patients. In addition, human studies do not consider genetic background as variable although human populations are genetically very diverse. Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection. Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans. The top-regulated genes in humans were also differentially regulated in mice. We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans. Furthermore, mouse studies allow confirmation of findings in humans in a well-controlled experimental system adding enormous value to the understanding of expression and function of human candidate genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00335-018-9750-y) contains supplementary material, which is available to authorized users.",2018 Jun 15,"['Kollmus, Heike', 'Pilzner, Carolin', 'Leist, Sarah R.', 'Heise, Mark', 'Geffers, Robert', 'Schughart, Klaus']",Mamm Genome,,,False
36cdca7614e11f1a8fefafa2aa18756f1e2c8478,PMC,Of mice and men: the host response to influenza virus infection,http://dx.doi.org/10.1007/s00335-018-9750-y,PMC6132725,29947965,CC BY,"Influenza virus (IV) infections represent a very serious public health problem. At present, no established biomarkers exist to support diagnosis for respiratory viral infections and more importantly for severe IV disease. Studies in animal models are extremely important to understand the biological, genetic, and environmental factors that contribute to severe IV disease and to validate biomarker candidates from human studies. However, mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs, whereas in humans almost all studies use peripheral blood from patients. In addition, human studies do not consider genetic background as variable although human populations are genetically very diverse. Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection. Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans. The top-regulated genes in humans were also differentially regulated in mice. We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans. Furthermore, mouse studies allow confirmation of findings in humans in a well-controlled experimental system adding enormous value to the understanding of expression and function of human candidate genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00335-018-9750-y) contains supplementary material, which is available to authorized users.",2018 Jun 15,"['Kollmus, Heike', 'Pilzner, Carolin', 'Leist, Sarah R.', 'Heise, Mark', 'Geffers, Robert', 'Schughart, Klaus']",Mamm Genome,,,False
a29e3cf7ae6f7c079d5e354e3b820470c002475c,PMC,Of mice and men: the host response to influenza virus infection,http://dx.doi.org/10.1007/s00335-018-9750-y,PMC6132725,29947965,CC BY,"Influenza virus (IV) infections represent a very serious public health problem. At present, no established biomarkers exist to support diagnosis for respiratory viral infections and more importantly for severe IV disease. Studies in animal models are extremely important to understand the biological, genetic, and environmental factors that contribute to severe IV disease and to validate biomarker candidates from human studies. However, mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs, whereas in humans almost all studies use peripheral blood from patients. In addition, human studies do not consider genetic background as variable although human populations are genetically very diverse. Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection. Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans. The top-regulated genes in humans were also differentially regulated in mice. We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans. Furthermore, mouse studies allow confirmation of findings in humans in a well-controlled experimental system adding enormous value to the understanding of expression and function of human candidate genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00335-018-9750-y) contains supplementary material, which is available to authorized users.",2018 Jun 15,"['Kollmus, Heike', 'Pilzner, Carolin', 'Leist, Sarah R.', 'Heise, Mark', 'Geffers, Robert', 'Schughart, Klaus']",Mamm Genome,,,False
f1ffc59cc5cc6dceeec2f971e8c14dd37a722ea8,PMC,Of mice and men: the host response to influenza virus infection,http://dx.doi.org/10.1007/s00335-018-9750-y,PMC6132725,29947965,CC BY,"Influenza virus (IV) infections represent a very serious public health problem. At present, no established biomarkers exist to support diagnosis for respiratory viral infections and more importantly for severe IV disease. Studies in animal models are extremely important to understand the biological, genetic, and environmental factors that contribute to severe IV disease and to validate biomarker candidates from human studies. However, mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs, whereas in humans almost all studies use peripheral blood from patients. In addition, human studies do not consider genetic background as variable although human populations are genetically very diverse. Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection. Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans. The top-regulated genes in humans were also differentially regulated in mice. We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans. Furthermore, mouse studies allow confirmation of findings in humans in a well-controlled experimental system adding enormous value to the understanding of expression and function of human candidate genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00335-018-9750-y) contains supplementary material, which is available to authorized users.",2018 Jun 15,"['Kollmus, Heike', 'Pilzner, Carolin', 'Leist, Sarah R.', 'Heise, Mark', 'Geffers, Robert', 'Schughart, Klaus']",Mamm Genome,,,False
9175e1d35d5fce4b6845600c9dfaf243954ca345,PMC,Of mice and men: the host response to influenza virus infection,http://dx.doi.org/10.1007/s00335-018-9750-y,PMC6132725,29947965,CC BY,"Influenza virus (IV) infections represent a very serious public health problem. At present, no established biomarkers exist to support diagnosis for respiratory viral infections and more importantly for severe IV disease. Studies in animal models are extremely important to understand the biological, genetic, and environmental factors that contribute to severe IV disease and to validate biomarker candidates from human studies. However, mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs, whereas in humans almost all studies use peripheral blood from patients. In addition, human studies do not consider genetic background as variable although human populations are genetically very diverse. Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection. Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans. The top-regulated genes in humans were also differentially regulated in mice. We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans. Furthermore, mouse studies allow confirmation of findings in humans in a well-controlled experimental system adding enormous value to the understanding of expression and function of human candidate genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00335-018-9750-y) contains supplementary material, which is available to authorized users.",2018 Jun 15,"['Kollmus, Heike', 'Pilzner, Carolin', 'Leist, Sarah R.', 'Heise, Mark', 'Geffers, Robert', 'Schughart, Klaus']",Mamm Genome,,,False
0c6f5af64219028a67bb7786cfaad3f80d394bb7,PMC,Of mice and men: the host response to influenza virus infection,http://dx.doi.org/10.1007/s00335-018-9750-y,PMC6132725,29947965,CC BY,"Influenza virus (IV) infections represent a very serious public health problem. At present, no established biomarkers exist to support diagnosis for respiratory viral infections and more importantly for severe IV disease. Studies in animal models are extremely important to understand the biological, genetic, and environmental factors that contribute to severe IV disease and to validate biomarker candidates from human studies. However, mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs, whereas in humans almost all studies use peripheral blood from patients. In addition, human studies do not consider genetic background as variable although human populations are genetically very diverse. Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection. Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans. The top-regulated genes in humans were also differentially regulated in mice. We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans. Furthermore, mouse studies allow confirmation of findings in humans in a well-controlled experimental system adding enormous value to the understanding of expression and function of human candidate genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00335-018-9750-y) contains supplementary material, which is available to authorized users.",2018 Jun 15,"['Kollmus, Heike', 'Pilzner, Carolin', 'Leist, Sarah R.', 'Heise, Mark', 'Geffers, Robert', 'Schughart, Klaus']",Mamm Genome,,,False
eba711fd327b76c19d64478c5df295313e041f8a,PMC,Of mice and men: the host response to influenza virus infection,http://dx.doi.org/10.1007/s00335-018-9750-y,PMC6132725,29947965,CC BY,"Influenza virus (IV) infections represent a very serious public health problem. At present, no established biomarkers exist to support diagnosis for respiratory viral infections and more importantly for severe IV disease. Studies in animal models are extremely important to understand the biological, genetic, and environmental factors that contribute to severe IV disease and to validate biomarker candidates from human studies. However, mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs, whereas in humans almost all studies use peripheral blood from patients. In addition, human studies do not consider genetic background as variable although human populations are genetically very diverse. Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection. Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans. The top-regulated genes in humans were also differentially regulated in mice. We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans. Furthermore, mouse studies allow confirmation of findings in humans in a well-controlled experimental system adding enormous value to the understanding of expression and function of human candidate genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00335-018-9750-y) contains supplementary material, which is available to authorized users.",2018 Jun 15,"['Kollmus, Heike', 'Pilzner, Carolin', 'Leist, Sarah R.', 'Heise, Mark', 'Geffers, Robert', 'Schughart, Klaus']",Mamm Genome,,,False
68139e318bd8880a6b11f4dee8779ff0bd3a83a4,PMC,Of mice and men: the host response to influenza virus infection,http://dx.doi.org/10.1007/s00335-018-9750-y,PMC6132725,29947965,CC BY,"Influenza virus (IV) infections represent a very serious public health problem. At present, no established biomarkers exist to support diagnosis for respiratory viral infections and more importantly for severe IV disease. Studies in animal models are extremely important to understand the biological, genetic, and environmental factors that contribute to severe IV disease and to validate biomarker candidates from human studies. However, mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs, whereas in humans almost all studies use peripheral blood from patients. In addition, human studies do not consider genetic background as variable although human populations are genetically very diverse. Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection. Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans. The top-regulated genes in humans were also differentially regulated in mice. We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans. Furthermore, mouse studies allow confirmation of findings in humans in a well-controlled experimental system adding enormous value to the understanding of expression and function of human candidate genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00335-018-9750-y) contains supplementary material, which is available to authorized users.",2018 Jun 15,"['Kollmus, Heike', 'Pilzner, Carolin', 'Leist, Sarah R.', 'Heise, Mark', 'Geffers, Robert', 'Schughart, Klaus']",Mamm Genome,,,True
83b302c75378ce58e35ef93b6214a6ec330998c1,PMC,Modeling pathogenesis of emergent and pre-emergent human coronaviruses in mice,http://dx.doi.org/10.1007/s00335-018-9760-9,PMC6132729,30043100,CC BY,"The emergence of highly pathogenic human coronaviruses (hCoVs) in the last two decades has illuminated their potential to cause high morbidity and mortality in human populations and disrupt global economies. Global pandemic concerns stem from their high mortality rates, capacity for human-to-human spread by respiratory transmission, and complete lack of approved therapeutic countermeasures. Limiting disease may require the development of virus-directed and host-directed therapeutic strategies due to the acute etiology of hCoV infections. Therefore, understanding how hCoV–host interactions cause pathogenic outcomes relies upon mammalian models that closely recapitulate the pathogenesis of hCoVs in humans. Pragmatism has largely been the driving force underpinning mice as highly effective mammalian models for elucidating hCoV–host interactions that govern pathogenesis. Notably, tractable mouse genetics combined with hCoV reverse genetic systems has afforded the concomitant manipulation of virus and host genetics to evaluate virus–host interaction networks in disease. In addition to assessing etiologies of known hCoVs, mouse models have clinically predictive value as tools to appraise potential disease phenotypes associated with pre-emergent CoVs. Knowledge of CoV pathogenic potential before it crosses the species barrier into the human population provides a highly desirable preclinical platform for addressing global pathogen preparedness, an overarching directive of the World Health Organization. Although we recognize that results obtained in robust mouse models require evaluation in non-human primates, we focus this review on the current state of hCoV mouse models, their use as tractable complex genetic organisms for untangling complex hCoV–host interactions, and as pathogenesis models for preclinical evaluation of novel therapeutic interventions.",2018 Jul 24,"['Cockrell, Adam S.', 'Leist, Sarah R.', 'Douglas, Madeline G.', 'Baric, Ralph S.']",Mamm Genome,,,True
a4fe3ad28d82650b92cbbfe942f2714038e83ba3,PMC,Increasing the number of available ranks in virus taxonomy from five to ten and adopting the Baltimore classes as taxa at the basal rank,http://dx.doi.org/10.1007/s00705-018-3915-6,PMC6132925,29942981,CC BY,This opinion article makes a case for increasing the number of ranks used in virus taxonomy from the current five to ten (as are used to classify cellular life forms) and placing the Baltimore classes in the proposed basal rank of domain. These suggestions aim at initiating the process of accommodation of Baltimore classes in virus taxonomy and extension of the virus taxonomy scale to encompass also the most distant relationships.,2018 Jun 26,"Gorbalenya, Alexander E.",Arch Virol,,,True
f1b81916fac1ca3d50dde774df2e1bb26bf0fb39,PMC,The vacuolar-type ATPase inhibitor archazolid increases tumor cell adhesion to endothelial cells by accumulating extracellular collagen,http://dx.doi.org/10.1371/journal.pone.0203053,PMC6133348,30204757,CC BY,"The vacuolar-type H(+)-ATPase (v-ATPase) is the major proton pump that acidifies intracellular compartments of eukaryotic cells. Since the inhibition of v-ATPase resulted in anti-tumor and anti-metastatic effects in different tumor models, this enzyme has emerged as promising strategy against cancer. Here, we used the well-established v-ATPase inhibitor archazolid, a natural product first isolated from the myxobacterium Archangium gephyra, to study the consequences of v-ATPase inhibition in endothelial cells (ECs), in particular on the interaction between ECs and cancer cells, which has been neglected so far. Human endothelial cells treated with archazolid showed an increased adhesion of tumor cells, whereas the transendothelial migration of tumor cells was reduced. The adhesion process was independent from the EC adhesion molecules ICAM-1, VCAM-1, E-selectin and N-cadherin. Instead, the adhesion was mediated by β1-integrins expressed on tumor cells, as blocking of the integrin β1 subunit reversed this process. Tumor cells preferentially adhered to the β1-integrin ligand collagen and archazolid led to an increase in the amount of collagen on the surface of ECs. The accumulation of collagen was accompanied by a strong decrease of the expression and activity of the protease cathepsin B. Overexpression of cathepsin B in ECs prevented the capability of archazolid to increase the adhesion of tumor cells onto ECs. Our study demonstrates that the inhibition of v-ATPase by archazolid induces a pro-adhesive phenotype in endothelial cells that promotes their interaction with cancer cells, whereas the transmigration of tumor cells was reduced. These findings further support archazolid as a promising anti-metastatic compound.",2018 Sep 11,"['Luong, Betty', 'Schwenk, Rebecca', 'Bräutigam, Jacqueline', 'Müller, Rolf', 'Menche, Dirk', 'Bischoff, Iris', 'Fürst, Robert']",PLoS One,,,True
ab402ceaf0dd0684e8e84b9204c81fdc48dc0e54,PMC,Phosphoproteomic-based kinase profiling early in influenza virus infection identifies GRK2 as antiviral drug target,http://dx.doi.org/10.1038/s41467-018-06119-y,PMC6133941,30206219,CC BY,"Although annual influenza epidemics affect around 10% of the global population, current treatment options are limited and development of new antivirals is needed. Here, using quantitative phosphoproteomics, we reveal the unique phosphoproteome dynamics that occur in the host cell within minutes of influenza A virus (IAV) infection. We uncover cellular kinases required for the observed signaling pattern and find that inhibition of selected candidates, such as the G protein-coupled receptor kinase 2 (GRK2), leads to decreased IAV replication. As GRK2 has emerged as drug target in heart disease, we focus on its role in IAV infection and show that it is required for viral uncoating. Replication of seasonal and pandemic IAVs is severely decreased by specific GRK2 inhibitors in primary human airway cultures and in mice. Our study reveals the IAV-induced changes to the cellular phosphoproteome and identifies GRK2 as crucial node of the kinase network that enables IAV replication.",2018 Sep 11,"['Yángüez, Emilio', 'Hunziker, Annika', 'Dobay, Maria Pamela', 'Yildiz, Soner', 'Schading, Simon', 'Elshina, Elizaveta', 'Karakus, Umut', 'Gehrig, Peter', 'Grossmann, Jonas', 'Dijkman, Ronald', 'Schmolke, Mirco', 'Stertz, Silke']",Nat Commun,,,False
550568fe1bf0b6fc5b2fab39e4a3122f4bc5d0ca,PMC,Phosphoproteomic-based kinase profiling early in influenza virus infection identifies GRK2 as antiviral drug target,http://dx.doi.org/10.1038/s41467-018-06119-y,PMC6133941,30206219,CC BY,"Although annual influenza epidemics affect around 10% of the global population, current treatment options are limited and development of new antivirals is needed. Here, using quantitative phosphoproteomics, we reveal the unique phosphoproteome dynamics that occur in the host cell within minutes of influenza A virus (IAV) infection. We uncover cellular kinases required for the observed signaling pattern and find that inhibition of selected candidates, such as the G protein-coupled receptor kinase 2 (GRK2), leads to decreased IAV replication. As GRK2 has emerged as drug target in heart disease, we focus on its role in IAV infection and show that it is required for viral uncoating. Replication of seasonal and pandemic IAVs is severely decreased by specific GRK2 inhibitors in primary human airway cultures and in mice. Our study reveals the IAV-induced changes to the cellular phosphoproteome and identifies GRK2 as crucial node of the kinase network that enables IAV replication.",2018 Sep 11,"['Yángüez, Emilio', 'Hunziker, Annika', 'Dobay, Maria Pamela', 'Yildiz, Soner', 'Schading, Simon', 'Elshina, Elizaveta', 'Karakus, Umut', 'Gehrig, Peter', 'Grossmann, Jonas', 'Dijkman, Ronald', 'Schmolke, Mirco', 'Stertz, Silke']",Nat Commun,,,True
bf0eb828cf6cfdca6328f464b58631006257dfd2,PMC,Phosphoproteomic-based kinase profiling early in influenza virus infection identifies GRK2 as antiviral drug target,http://dx.doi.org/10.1038/s41467-018-06119-y,PMC6133941,30206219,CC BY,"Although annual influenza epidemics affect around 10% of the global population, current treatment options are limited and development of new antivirals is needed. Here, using quantitative phosphoproteomics, we reveal the unique phosphoproteome dynamics that occur in the host cell within minutes of influenza A virus (IAV) infection. We uncover cellular kinases required for the observed signaling pattern and find that inhibition of selected candidates, such as the G protein-coupled receptor kinase 2 (GRK2), leads to decreased IAV replication. As GRK2 has emerged as drug target in heart disease, we focus on its role in IAV infection and show that it is required for viral uncoating. Replication of seasonal and pandemic IAVs is severely decreased by specific GRK2 inhibitors in primary human airway cultures and in mice. Our study reveals the IAV-induced changes to the cellular phosphoproteome and identifies GRK2 as crucial node of the kinase network that enables IAV replication.",2018 Sep 11,"['Yángüez, Emilio', 'Hunziker, Annika', 'Dobay, Maria Pamela', 'Yildiz, Soner', 'Schading, Simon', 'Elshina, Elizaveta', 'Karakus, Umut', 'Gehrig, Peter', 'Grossmann, Jonas', 'Dijkman, Ronald', 'Schmolke, Mirco', 'Stertz, Silke']",Nat Commun,,,False
554d4209692f1b384ec738f3c74b110ccf5e8dbb,PMC,Phosphoproteomic-based kinase profiling early in influenza virus infection identifies GRK2 as antiviral drug target,http://dx.doi.org/10.1038/s41467-018-06119-y,PMC6133941,30206219,CC BY,"Although annual influenza epidemics affect around 10% of the global population, current treatment options are limited and development of new antivirals is needed. Here, using quantitative phosphoproteomics, we reveal the unique phosphoproteome dynamics that occur in the host cell within minutes of influenza A virus (IAV) infection. We uncover cellular kinases required for the observed signaling pattern and find that inhibition of selected candidates, such as the G protein-coupled receptor kinase 2 (GRK2), leads to decreased IAV replication. As GRK2 has emerged as drug target in heart disease, we focus on its role in IAV infection and show that it is required for viral uncoating. Replication of seasonal and pandemic IAVs is severely decreased by specific GRK2 inhibitors in primary human airway cultures and in mice. Our study reveals the IAV-induced changes to the cellular phosphoproteome and identifies GRK2 as crucial node of the kinase network that enables IAV replication.",2018 Sep 11,"['Yángüez, Emilio', 'Hunziker, Annika', 'Dobay, Maria Pamela', 'Yildiz, Soner', 'Schading, Simon', 'Elshina, Elizaveta', 'Karakus, Umut', 'Gehrig, Peter', 'Grossmann, Jonas', 'Dijkman, Ronald', 'Schmolke, Mirco', 'Stertz, Silke']",Nat Commun,,,True
ce50fd91c0c1bbd6f3f9de6a231a9cd41700108b,PMC,Antiviral innate immune response in non-myeloid cells is augmented by chloride ions via an increase in intracellular hypochlorous acid levels,http://dx.doi.org/10.1038/s41598-018-31936-y,PMC6134045,30206371,CC BY,"Phagocytes destroy ingested microbes by producing hypochlorous acid (HOCl) from chloride ions (Cl(−)) and hydrogen peroxide within phagolysosomes, using the enzyme myeloperoxidase. HOCl, the active ingredient in bleach, has antibacterial/antiviral properties. As myeloperoxidase is needed for HOCl production, non-myeloid cells are considered incapable of producing HOCl. Here, we show that epithelial, fibroblast and hepatic cells have enhanced antiviral activity in the presence of increasing concentrations of sodium chloride (NaCl). Replication of enveloped/non-enveloped, DNA (herpes simplex virus-1, murine gammaherpesvirus 68) and RNA (respiratory syncytial virus, influenza A virus, human coronavirus 229E, coxsackievirus B3) viruses are inhibited in a dose-dependent manner. Whilst treatment with sodium channel inhibitors did not prevent NaCl-mediated virus inhibition, a chloride channel inhibitor reversed inhibition by NaCl, suggesting intracellular chloride is required for antiviral activity. Inhibition is also reversed in the presence of 4-aminobenzoic hydrazide, a myeloperoxidase inhibitor, suggesting epithelial cells have a peroxidase to convert Cl(−) to HOCl. A significant increase in intracellular HOCl production is seen early in infection. These data suggest that non-myeloid cells possess an innate antiviral mechanism dependent on the availability of Cl(−) to produce HOCl. Antiviral activity against a broad range of viral infections can be augmented by increasing availability of NaCl.",2018 Sep 11,"['Ramalingam, Sandeep', 'Cai, Baiyi', 'Wong, Junsheng', 'Twomey, Matthew', 'Chen, Rui', 'Fu, Rebecca M.', 'Boote, Toby', 'McCaughan, Hugh', 'Griffiths, Samantha J.', 'Haas, Jürgen G.']",Sci Rep,,,True
0dbb8e8757f40e57ded9443666880d99a63c8d7e,PMC,Oral immunization with a novel attenuated Salmonella Gallinarum encoding infectious bronchitis virus spike protein induces protective immune responses against fowl typhoid and infectious bronchitis in chickens,http://dx.doi.org/10.1186/s13567-018-0588-9,PMC6134591,30208963,CC BY,"Fowl typhoid (FT), a septicemic disease caused by Salmonella Gallinarum (SG), and infectious bronchitis (IB) are two economically important avian diseases that affect poultry industry worldwide. Herein, we exploited a live attenuated SG mutant, JOL967, to deliver spike (S) protein 1 of IB virus (V) to elicit protective immunity against both FT and IB in chickens. The codon optimized S1 nucleotide sequence was cloned in-frame into a prokaryotic constitutive expression vector, pJHL65. Subsequently, empty pJHL65 or recombinant pJHL65-S1 plasmid was electroporated into JOL967 and the resultant clones were designated as JOL2068 and JOL2077, respectively. Our results demonstrated that the chickens vaccinated once orally with JOL2077 elicited significantly (p < 0.05) higher IBV-specific humoral and cell-mediated immunity compared to JOL2068 and PBS control groups. Consequently, on challenge with the virulent IBV strain at 28(th) day post-vaccination, JOL2077 vaccinated birds displayed significantly (p < 0.05) lower inflammatory lesions in virus-targeted tissues compared to control groups. Furthermore, 33.3% (2 of 6) of birds vaccinated with JOL2077 vaccine had shown virus recovery from tracheal tissues compared to 100% (6 of 6) recovery obtained in both the control groups. Against wild-type SG lethal challenge, both JOL2077 and JOL2068 vaccinated groups exhibited only 10% mortality compared to 80% mortality observed in PBS control group. In conclusion, we show that JOL2077 can induce efficient IBV- and carrier-specific protective immunity and can act as a bivalent vaccine against FT and IB. Further studies are warranted to investigate the potential of JOL2077 vaccine in broiler and young layer birds. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13567-018-0588-9) contains supplementary material, which is available to authorized users.",2018 Sep 12,"['Hajam, Irshad Ahmed', 'Kim, Jehyoung', 'Lee, John Hwa']",Vet Res,,,True
0b65341c3090421acaac37ec4c93212277be55bb,PMC,Comparative proteomic analysis reveals different responses in porcine lymph nodes to virulent and attenuated homologous African swine fever virus strains,http://dx.doi.org/10.1186/s13567-018-0585-z,PMC6134756,30208957,CC BY,"African swine fever (ASF) is a pathology of pigs against which there is no treatment or vaccine. Understanding the equilibrium between innate and adaptive protective responses and immune pathology might contribute to the development of strategies against ASFV. Here we compare, using a proteomic approach, the course of the in vivo infection caused by two homologous strains: the virulent E75 and the attenuated E75CV1. Our results show a progressive loss of proteins by day 7 post-infection (pi) with E75, reflecting tissue destruction. Many signal pathways were affected by both infections but in different ways and extensions. Cytoskeletal remodelling and clathrin-endocytosis were affected by both isolates, while a greater number of proteins involved on inflammatory and immunological pathways were altered by E75CV1. 14-3-3 mediated signalling, related to immunity and apoptosis, was inhibited by both isolates. The implication of the Rho GTPases by E75CV1 throughout infection is also evident. Early events reflected the lack of E75 recognition by the immune system, an evasion strategy acquired by the virulent strains, and significant changes at 7 days post-infection (dpi), coinciding with the peak of infection and the time of death. The protein signature at day 31 pi with E75CV1 seems to reflect events observed at 1 dpi, including the upregulation of proteosomal subunits and molecules described as autoantigens (vimentin, HSPB1, enolase and lymphocyte cytosolic protein 1), which allow the speculation that auto-antibodies could contribute to chronic ASFV infections. Therefore, the use of proteomics could help understand ASFV pathogenesis and immune protection, opening new avenues for future research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13567-018-0585-z) contains supplementary material, which is available to authorized users.",2018 Sep 12,"['Herrera-Uribe, Júber', 'Jiménez-Marín, Ángeles', 'Lacasta, Anna', 'Monteagudo, Paula L.', 'Pina-Pedrero, Sonia', 'Rodríguez, Fernando', 'Moreno, Ángela', 'Garrido, Juan J.']",Vet Res,,,True
778e81157f2312199105d67938e88bf0ec559130,PMC,Stabilizing HIV-1 envelope glycoprotein trimers to induce neutralizing antibodies,http://dx.doi.org/10.1186/s12977-018-0445-y,PMC6134781,30208933,CC BY,"An effective HIV-1 vaccine probably will need to be able to induce broadly neutralizing HIV-1 antibodies (bNAbs) in order to be efficacious. The many bNAbs that have been isolated from HIV-1 infected patients illustrate that the human immune system is able to elicit this type of antibodies. The elucidation of the structure of the HIV-1 envelope glycoprotein (Env) trimer has further fueled the search for Env immunogens that induce bNAbs, but while native Env trimer mimetics are often capable of inducing strain-specific neutralizing antibodies (NAbs) against the parental virus, they have not yet induced potent bNAb responses. To improve the performance of Env trimer immunogens, researchers have studied the immune responses that Env trimers have induced in animals; they have evaluated how to best use Env trimers in various immunization regimens; and they have engineered increasingly stabilized Env trimer variants. Here, we review the different approaches that have been used to increase the stability of HIV-1 Env trimer immunogens with the aim of improving the induction of NAbs. In particular, we draw parallels between the various approaches to stabilize Env trimers and ones that have been used by nature in extremophile microorganisms in order to survive in extreme environmental conditions.",2018 Sep 12,"['Torrents de la Peña, Alba', 'Sanders, Rogier W.']",Retrovirology,,,True
aeaf5bd4725051f6926d06450566673d1cc4a639,PMC,Genomic characterization and infectivity of a novel SARS-like coronavirus in Chinese bats,http://dx.doi.org/10.1038/s41426-018-0155-5,PMC6135831,30209269,CC BY,"SARS coronavirus (SARS-CoV), the causative agent of the large SARS outbreak in 2003, originated in bats. Many SARS-like coronaviruses (SL-CoVs) have been detected in bats, particularly those that reside in China, Europe, and Africa. To further understand the evolutionary relationship between SARS-CoV and its reservoirs, 334 bats were collected from Zhoushan city, Zhejiang province, China, between 2015 and 2017. PCR amplification of the conserved coronaviral protein RdRp detected coronaviruses in 26.65% of bats belonging to this region, and this number was influenced by seasonal changes. Full genomic analyses of the two new SL-CoVs from Zhoushan (ZXC21 and ZC45) showed that their genomes were 29,732 nucleotides (nt) and 29,802 nt in length, respectively, with 13 open reading frames (ORFs). These results revealed 81% shared nucleotide identity with human/civet SARS CoVs, which was more distant than that observed previously for bat SL-CoVs in China. Importantly, using pathogenic tests, we found that the virus can reproduce and cause disease in suckling rats, and further studies showed that the virus-like particles can be observed in the brains of suckling rats by electron microscopy. Thus, this study increased our understanding of the genetic diversity of the SL-CoVs carried by bats and also provided a new perspective to study the possibility of cross-species transmission of SL-CoVs using suckling rats as an animal model.",2018 Sep 12,"['Hu, Dan', 'Zhu, Changqiang', 'Ai, Lele', 'He, Ting', 'Wang, Yi', 'Ye, Fuqiang', 'Yang, Lu', 'Ding, Chenxi', 'Zhu, Xuhui', 'Lv, Ruicheng', 'Zhu, Jin', 'Hassan, Bachar', 'Feng, Youjun', 'Tan, Weilong', 'Wang, Changjun']",Emerg Microbes Infect,,,True
123db7e17bb17a0d4ff1e7ef87cb629d6ac78125,PMC,Could human coronavirus OC43 have co-evolved with early humans?,http://dx.doi.org/10.1590/1678-4685-GMB-2017-0192,PMC6136381,30004106,CC BY,"This paper reports on an investigation of the role of codon usage evolution on the suggested bovine-to-human spillover of Bovine coronavirus (BCoV), an enteric/respiratory virus of cattle, resulting in the emergence of the exclusively respiratory Human coronavirus OC43 (HCoV-OC43). Analyses based on full genomes of BCoV and HCoV-OC43 and on both human and bovine mRNAs sequences of cholecystokinin (CCK) and surfactant protein 1 A (SFTP1-A), representing the enteric and respiratory tract codon usage, respectively, have shown natural selection leading to optimization or deoptimization of viral codon usage to the human enteric and respiratory tracts depending on the virus genes under consideration. A higher correlation was found for the nucleotide distance at the 3(rd) nucleotide position of codons and codon usage optimization to the human respiratory tract when BCoV and HCoV-OC43 were compared. An MCC tree based on relative synonymous codon usage (RSCU) data integrating data from both viruses and hosts into a same analysis indicated three putative host/virus contact dates ranging from 1.54E8 to 2.44E5 years ago, suggesting that an ancestor coronavirus might have followed human evolution.",2018 Jun 28 Jul-Sep,"Brandão, Paulo Eduardo",Genet Mol Biol,,,True
e5230a23f4c70587a3cd4c19f54ae685125673a2,PMC,"Melioidosis in the Western Indian Ocean and the Importance of Improving Diagnosis, Surveillance, and Molecular Typing",http://dx.doi.org/10.3390/tropicalmed3010030,PMC6136609,30274427,CC BY,"Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an infectious disease of humans or animals, and the specific environmental conditions that are present in western Indian Ocean islands are particularly suitable for the establishment/survival of B. pseudomallei. Indeed, an increasing number of new cases have been reported in this region (Madagascar, Mauritius, Réunion (France), and Seychelles, except Comoros and Mayotte (France)), and are described in this review. Our review clearly points out that further studies are needed in order to investigate the real incidence and burden of melioidosis in the western Indian Ocean and especially Madagascar, since it is likely to be higher than currently reported. Thus, research and surveillance priorities were recommended (i) to improve awareness of melioidosis in the population and among clinicians; (ii) to improve diagnostics, in order to provide rapid and effective treatment; (iii) to implement a surveillance and reporting system in the western Indian Ocean; and (iv) to investigate the presence of B. pseudomallei in environmental samples, since we have demonstrated its presence in soil samples originating from the yard of a Madagascan case.",2018 Mar 7,"['Rakotondrasoa, Andriniaina', 'Issack, Mohammad Iqbal', 'Garin, Benoît', 'Biot, Fabrice', 'Valade, Eric', 'Wattiau, Pierre', 'Allou, Nicolas', 'Belmonte, Olivier', 'Bibi, Jastin', 'Price, Erin P.', 'Collard, Jean-Marc']",Trop Med Infect Dis,,,True
64b95b0bd76c83bc56ae6e150c4aad0dd36437a2,PMC,"Spotted Fever Rickettsiosis in a Wildlife Researcher in Sabah, Malaysia: A Case Study",http://dx.doi.org/10.3390/tropicalmed3010029,PMC6136627,30274426,CC BY,"We present evidence for a case of spotted fever rickettsiosis with severe complications in a young adult male. Although spotted fever group rickettsiae (SFGR) have been reported as the most prevalent cause of rickettsiosis in rural areas of Sabah, Malaysia since the 1980s, this is the first detailed case report of suspected SFGR in the state. Current data on the prevalence, type, and thorough clinical reports on complications of SFGR and other rickettsioses in Sabah is lacking and required to raise the awareness of such diseases. There is a need to emphasize the screening of rickettsioses to medical personnel and to encourage the use of appropriate antibiotics as early treatment for nonspecific febrile illnesses in this region. Suspected rickettsioses need to be considered as one of the differential diagnoses for patients presenting with acute febrile illness for laboratory investigations, and early treatment instituted.",2018 Mar 6,"['Salgado Lynn, Milena', 'William, Timothy', 'Tanganuchitcharnchai, Ampai', 'Jintaworn, Suthatip', 'Thaipadungpanit, Janjira', 'Lee, Mei Ho', 'Jalius, Cyrlen', 'Daszak, Peter', 'Goossens, Benoît', 'Hughes, Tom', 'Blacksell, Stuart D.']",Trop Med Infect Dis,,,True
c4f2c649c3390b0a84ae38733bcbb9dfd054ccfa,PMC,Sino-Australian University Partnership in Health Management Education,http://dx.doi.org/10.3389/fpubh.2018.00251,PMC6137234,30246005,CC BY,"This paper outlines a successful partnership program between La Trobe University in Melbourne Australia, and Harbin Medical University in Harbin, China. These two universities have been collaborating for more than 15 years to provide a comprehensive Master of Health Administration program that adapts the Australian curriculum to meet the rapidly increasing need for qualified health services managers throughout China. This paper describes the mechanisms by which the joint programs were developed and how the two universities work together in partnership to continually improve the program components and outcomes, taking into account the significant differences in context and cultures. Since 2001, La Trobe University has enrolled about 1000 Chinese health services managers, with 721 completing a Master's degree, who are now having increasing influence on the reforms of the Chinese health care system. The partnership has enriched Australian knowledge of Chinese culture and values, as well as the Chinese health system and health policies, as evidenced by the large volume of joint publications. The profession of health management has been substantially strengthened in China, and working together, Chinese and Australian academics have had demonstrated impact on enhancing the reforms of the Chinese public health system. Further studies, with sufficient funds for data collection, are needed to evaluate the long-term impacts of transnational programs on academic and health system development in China.",2018 Sep 7,"['Leggat, Sandra G.', 'Liu, Chaojie', 'Wu, Qunhong']",Front Public Health,,,True
cc65837c07beb5eedce242ab30fa377907f22546,PMC,Association between semi-quantitative microbial load and respiratory symptoms among Thai military recruits: a prospective cohort study,http://dx.doi.org/10.1186/s12879-018-3358-4,PMC6137728,30217168,CC BY,"BACKGROUND: Multiplex real-time polymerase chain reaction assays have improved diagnostic sensitivity for a wide range of pathogens. However, co-detection of multiple agents and bacterial colonization make it difficult to distinguish between asymptomatic infection or illness aetiology. We assessed whether semi-quantitative microbial load data can differentiate between symptomatic and asymptomatic states for common respiratory pathogens. METHODS: We obtained throat and nasal swab samples from military trainees at two Thai Army barracks. Specimens were collected at the start and end of 10-week training periods (non-acute samples), and from individuals who developed upper respiratory tract infection during training (acute samples). We analysed the samples using a commercial multiplex respiratory panel comprising 33 bacterial, viral and fungal targets. We used random effects tobit models to compare cycle threshold (Ct) value distributions from non-acute and acute samples. RESULTS: We analysed 341 non-acute and 145 acute swab samples from 274 participants. Haemophilus influenzae type B was the most commonly detected microbe (77.4% of non-acute and 64.8% of acute samples). In acute samples, nine specific microbe pairs were detected more frequently than expected by chance. Regression models indicated significantly lower microbial load in non-acute relative to acute samples for H. influenzae non-type B, Streptococcus pneumoniae and rhinovirus, although it was not possible to identify a Ct-value threshold indicating causal etiology for any of these organisms. CONCLUSIONS: Semi-quantitative measures of microbial concentration did not reliably differentiate between illness and asymptomatic colonization, suggesting that clinical symptoms may not always be directly related to microbial load for common respiratory infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3358-4) contains supplementary material, which is available to authorized users.",2018 Sep 14,"['Tam, Clarence C.', 'Offeddu, Vittoria', 'Anderson, Kathryn B.', 'Weg, Alden L.', 'Macareo, Louis R.', 'Ellison, Damon W.', 'Rangsin, Ram', 'Fernandez, Stefan', 'Gibbons, Robert V.', 'Yoon, In-Kyu', 'Simasathien, Sriluck']",BMC Infect Dis,,,True
511ac6ac4422cee5357b1b6ff0b59acbfe2402c5,PMC,Overview of the perceived risk of transboundary pig diseases in South Africa,http://dx.doi.org/10.4102/jsava.v86i1.1197,PMC6138123,26018934,CC BY,"Pig production is one of the most important animal agricultural activities in South Africa, and plays a definite role in providing food security for certain population groups in the country. As with all animal production systems, it is subject to the risk of outbreak of transboundary diseases. In the present overview, evaluations of the perceived risk of selected transboundary animal diseases of pigs, as collated from the willing participants from the provincial veterinary services of South Africa, are presented. A scenario tree revealed that infected but undetected pigs were the greatest perceived threat. The provincial veterinary services, according to participants in the study, face certain difficulties, including the reporting of disease and the flow of disease information amongst farmers. Perceived strengths in surveillance and disease monitoring include the swiftness of sample despatch to the national testing laboratory, as well as the ease of flow of information between the provincial and national agricultural authorities. The four factors were identified that were perceived to most influence animal health-service delivery: transport, access, livestock policy and resources. African swine fever was perceived to be the most important pig disease in South Africa. Because the decentralisation of veterinary services in South Africa was identified as a potential weakness, it is recommended that national and provincial veterinary services need to work together and interdependently to achieve centrally controlled surveillance systems. Regionally-coordinated surveillance activities for certain transboundary diseases were identified as needing priority for the southern African region. It is proposed that an emergency preparedness document be made available and regularly revised according to the potential risks identified on a continuous basis for South Africa.",2015 May 22,"['Mokoele, Japhta M.', 'van Rensburg, Leana Janse', 'van Lochem, Shanie', 'Bodenstein, Heinz', 'du Plessis, Jacolette', 'Carrington, Chris A.P.', 'Spencer, B. Tom', 'Fasina, Folorunso O.']",J S Afr Vet Assoc,,,True
4fc79293e3efdfd44b408d923b2448ac6a5ddd0d,PMC,A self-adjuvanted nanoparticle based vaccine against infectious bronchitis virus,http://dx.doi.org/10.1371/journal.pone.0203771,PMC6138407,30216376,CC BY,"Infectious bronchitis virus (IBV) affects poultry respiratory, renal and reproductive systems. Currently the efficacy of available live attenuated or killed vaccines against IBV has been challenged. We designed a novel IBV vaccine alternative using a highly innovative platform called Self-Assembling Protein Nanoparticle (SAPN). In this vaccine, B cell epitopes derived from the second heptad repeat (HR2) region of IBV spike proteins were repetitively presented in its native trimeric conformation. In addition, flagellin was co-displayed in the SAPN to achieve a self-adjuvanted effect. Three groups of chickens were immunized at four weeks of age with the vaccine prototype, IBV-Flagellin-SAPN, a negative-control construct Flagellin-SAPN or a buffer control. The immunized chickens were challenged with 5x10(4.7) EID50 IBV M41 strain. High antibody responses were detected in chickens immunized with IBV-Flagellin-SAPN. In ex vivo proliferation tests, peripheral mononuclear cells (PBMCs) derived from IBV-Flagellin-SAPN immunized chickens had a significantly higher stimulation index than that of PBMCs from chickens receiving Flagellin-SAPN. Chickens immunized with IBV-Flagellin-SAPN had a significant reduction of tracheal virus shedding and lesser tracheal lesion scores than did negative control chickens. The data demonstrated that the IBV-Flagellin-SAPN holds promise as a vaccine for IBV.",2018 Sep 14,"['Li, Jianping', 'Helal, Zeinab H.', 'Karch, Christopher P.', 'Mishra, Neha', 'Girshick, Theodore', 'Garmendia, Antonio', 'Burkhard, Peter', 'Khan, Mazhar I.']",PLoS One,,,True
8034d32d25d4075f4f59f5987728e4656d32ecd0,PMC,Untargeted analysis of the airway proteomes of children with respiratory infections using mass spectrometry based proteomics,http://dx.doi.org/10.1038/s41598-018-32072-3,PMC6138648,30217988,CC BY,"The upper airway – which consists mainly of the naso- and oro-pharynx - is the first point of contact between the respiratory system and microbial organisms that are ubiquitous in the environment. It has evolved highly specialised functions to address these constant threats whilst facilitating seamless respiratory exchange with the lower respiratory tract. Dysregulation of its critical homeostatic and defence functions can lead to ingress of pathogens into the lower respiratory tract, potentially leading to serious illness. Systems-wide proteomic tools may facilitate a better understanding of mechanisms in the upper airways in health and disease. In this study, we aimed to develop a mass spectrometry based proteomics method for characterizing the upper airways proteome. Naso- and oropharyngeal swab samples used in all our experiments had been eluted in the Universal Transport Media (UTM) containing significantly high levels of bovine serum albumin. Our proteomic experiments tested the optimal approach to characterize airway proteome on swab samples eluted in UTM based on the number of proteins identified without BSA depletion (Total proteome: Protocol A) and with its depletion using a commercial kit; Allprep, Qiagen (cellular proteome: Protocol B, Ci, and Cii). Observations and lessons drawn from protocol A, fed into the design and implementation of protocol B, and from B to protocol Ci and finally Cii. Label free proteome quantification was used in Protocol A (n = 6) and B (n = 4) while commercial TMT 10plex reagents were used for protocols Ci and ii (n = 83). Protocols Ci and ii were carried out under similar conditions except for the elution gradient: 3 h and 6 h respectively. Swab samples tested in this study were from infants and children with and without upper respiratory tract infections from Kilifi County Hospital on the Kenyan Coast. Protocol A had the least number of proteins identified (215) while B produced the highest number of protein identifications (2396). When Protocol B was modified through sample multiplexing with TMT to enable higher throughput (Protocol Ci), the number of protein identified reduced to 1432. Modification of protocol Ci by increasing the peptide elution time generated Protocol Cii that substantially increased the number of proteins identified to 1875. The coefficient of variation among the TMT runs in Protocol Cii was <20%. There was substantial overlap in the identity of proteins using the four protocols. Our method was were able to identify marker proteins characteristically expressed in the upper airway. We found high expression levels of signature nasopharyngeal and oral proteins, including BPIFA1/2 and AMY1A, as well as a high abundance of proteins related to innate and adaptive immune function in the upper airway. We have developed a sensitive systems-level proteomic assay for the systematic quantification of naso-oro-pharyngeal proteins. The assay will advance mechanistic studies of respiratory pathology, by providing an untargeted and hypothesis-free approach of examining the airway proteome.",2018 Sep 14,"['Sande, Charles J.', 'Mutunga, Martin', 'Muteti, Jacqueline', 'Berkley, James A.', 'Nokes, D. James', 'Njunge, James']",Sci Rep,,,False
a3980dbebf9ade61200fc033a91383e5974912ec,PMC,Untargeted analysis of the airway proteomes of children with respiratory infections using mass spectrometry based proteomics,http://dx.doi.org/10.1038/s41598-018-32072-3,PMC6138648,30217988,CC BY,"The upper airway – which consists mainly of the naso- and oro-pharynx - is the first point of contact between the respiratory system and microbial organisms that are ubiquitous in the environment. It has evolved highly specialised functions to address these constant threats whilst facilitating seamless respiratory exchange with the lower respiratory tract. Dysregulation of its critical homeostatic and defence functions can lead to ingress of pathogens into the lower respiratory tract, potentially leading to serious illness. Systems-wide proteomic tools may facilitate a better understanding of mechanisms in the upper airways in health and disease. In this study, we aimed to develop a mass spectrometry based proteomics method for characterizing the upper airways proteome. Naso- and oropharyngeal swab samples used in all our experiments had been eluted in the Universal Transport Media (UTM) containing significantly high levels of bovine serum albumin. Our proteomic experiments tested the optimal approach to characterize airway proteome on swab samples eluted in UTM based on the number of proteins identified without BSA depletion (Total proteome: Protocol A) and with its depletion using a commercial kit; Allprep, Qiagen (cellular proteome: Protocol B, Ci, and Cii). Observations and lessons drawn from protocol A, fed into the design and implementation of protocol B, and from B to protocol Ci and finally Cii. Label free proteome quantification was used in Protocol A (n = 6) and B (n = 4) while commercial TMT 10plex reagents were used for protocols Ci and ii (n = 83). Protocols Ci and ii were carried out under similar conditions except for the elution gradient: 3 h and 6 h respectively. Swab samples tested in this study were from infants and children with and without upper respiratory tract infections from Kilifi County Hospital on the Kenyan Coast. Protocol A had the least number of proteins identified (215) while B produced the highest number of protein identifications (2396). When Protocol B was modified through sample multiplexing with TMT to enable higher throughput (Protocol Ci), the number of protein identified reduced to 1432. Modification of protocol Ci by increasing the peptide elution time generated Protocol Cii that substantially increased the number of proteins identified to 1875. The coefficient of variation among the TMT runs in Protocol Cii was <20%. There was substantial overlap in the identity of proteins using the four protocols. Our method was were able to identify marker proteins characteristically expressed in the upper airway. We found high expression levels of signature nasopharyngeal and oral proteins, including BPIFA1/2 and AMY1A, as well as a high abundance of proteins related to innate and adaptive immune function in the upper airway. We have developed a sensitive systems-level proteomic assay for the systematic quantification of naso-oro-pharyngeal proteins. The assay will advance mechanistic studies of respiratory pathology, by providing an untargeted and hypothesis-free approach of examining the airway proteome.",2018 Sep 14,"['Sande, Charles J.', 'Mutunga, Martin', 'Muteti, Jacqueline', 'Berkley, James A.', 'Nokes, D. James', 'Njunge, James']",Sci Rep,,,True
a81fbdb3bc7956412cd686e72115f4cddf1090be,PMC,The Journey of in vivo Virus Engineered Dendritic Cells From Bench to Bedside: A Bumpy Road,http://dx.doi.org/10.3389/fimmu.2018.02052,PMC6141723,30254636,CC BY,"Dendritic cells (DCs) are recognized as highly potent antigen-presenting cells that are able to stimulate cytotoxic T lymphocyte (CTL) responses with antitumor activity. Consequently, DCs have been explored as cellular vaccines in cancer immunotherapy. To that end, DCs are modified with tumor antigens to enable presentation of antigen-derived peptides to CTLs. In this review we discuss the use of viral vectors for in situ modification of DCs, focusing on their clinical applications as anticancer vaccines. Among the viral vectors discussed are those derived from viruses belonging to the families of the Poxviridae, Adenoviridae, Retroviridae, Togaviridae, Paramyxoviridae, and Rhabdoviridae. We will further shed light on how the combination of viral vector-based vaccination with T-cell supporting strategies will bring this strategy to the next level.",2018 Sep 11,"['Goyvaerts, Cleo', 'Breckpot, Karine']",Front Immunol,,,True
fd80f38e8161b81dc184779877ca0bd283ac2d2d,PMC,Adenoviromics: Mining the Human Adenovirus Species D Genome,http://dx.doi.org/10.3389/fmicb.2018.02178,PMC6141750,30254627,CC BY,"Human adenovirus (HAdV) infections cause disease world-wide. Whole genome sequencing has now distinguished 90 distinct genotypes in 7 species (A-G). Over half of these 90 HAdVs fall within species D, with essentially all of the HAdV-D whole genome sequences generated in the last decade. Herein, we describe recent new findings made possible by mining of this expanded genome database, and propose future directions to elucidate new functional elements and new functions for previously known viral components.",2018 Sep 11,"['Ismail, Ashrafali M.', 'Lee, Ji Sun', 'Lee, Jeong Yoon', 'Singh, Gurdeep', 'Dyer, David W.', 'Seto, Donald', 'Chodosh, James', 'Rajaiya, Jaya']",Front Microbiol,,,True
27f21a68a6f074f434e506aee9492fa2c772847c,PMC,Novel protein chip for the detection of antibodies against infectious bronchitis virus,http://dx.doi.org/10.1186/s12917-018-1586-x,PMC6142349,30223836,CC BY,"BACKGROUND: Infectious bronchitis (IB) caused by the IB virus (IBV) can cause acute damage to chickens around the world. Therefore, rapid diagnosis and immune status determination are critical for controlling IBV outbreaks. Enzyme-linked immunosorbent assays (ELISAs) have been widely used in the detection of IBV antibodies in the early infection and continuous infection of IB because they are more sensitive and quicker than other diagnostic methods. RESULTS: We have developed two indirect microarray methods to detect antibodies against IBV: a chemiluminescent immunoassay test (CIT) and a rapid diagnostic test (RDT). IBV nonstructural protein 5 (nsp5) was expressed, purified from Escherichia coli, and used to spot the initiator integrated poly(dimethylsiloxane), which can provide a near “zero” background for serological assays. Compared with the IDEXX IBV Ab Test kit, CIT and RDT have a sensitivity and specificity of at least 98.88% and 91.67%, respectively. No cross-reaction was detected with antibodies against avian influenza virus subtypes (H5, H7, and H9), Newcastle disease virus, Marek’s disease virus, infectious bursal disease virus, and chicken anemia virus. The coefficients of variation of the reproducibility of the intra- and inter-assays for CIT ranged from 0.8 to 18.63%. The reproducibility of RDT was consistent with the original results. The application of the IBV nsp5 protein microarray showed that the positive rate of the CIT was 96.77%, that of the nsp5 ELISA was 91.40%, and that of the RDT was 90.32%. Furthermore, the RDT, which was visible to the naked eye, could be completed within 15 min. Our results indicated that compared with nsp5 ELISA, the CIT was more sensitive, and the RDT had similar positive rates but was faster. Furthermore, the two proposed methods were specific and stable. CONCLUSIONS: Two microarray assays, which were rapid, specific, sensitive, and relatively simple, were developed for the detection of an antibody against IBV. These methods can be of great value for the surveillance of pathogens and monitoring the efficiency of vaccination.",2018 Sep 17,"['Yan, Liping', 'Hu, Jianhua', 'Lei, Jing', 'Shi, Zhiyu', 'Xiao, Qian', 'Bi, Zhenwei', 'Yao, Lu', 'Li, Yuan', 'Chen, Yuqing', 'Fang, An', 'Li, Hui', 'Song, Suquan', 'Liao, Min', 'Zhou, Jiyong']",BMC Vet Res,,,True
843ef80437031ed9f9adcf3e7b6183b6b898d433,PMC,"Impact of Emerging, Re-Emerging and Zoonotic Viral Infectious Diseases, in a Virologist’s Perspective",http://dx.doi.org/10.2174/1874357901812010131,PMC6142664,30288201,CC BY,,2018 Aug 31,"Kobayashi, Nobumichi",Open Virol J,,,True
aa6fd0de59bb82e7c94b044d8145fbd50d7c9b9a,PMC,Zoonotic Viral Diseases of Equines and Their Impact on Human and Animal Health,http://dx.doi.org/10.2174/1874357901812010080,PMC6142672,30288197,CC BY,"INTRODUCTION: Zoonotic diseases are the infectious diseases that can be transmitted to human beings and vice versa from animals either directly or indirectly. These diseases can be caused by a range of organisms including bacteria, parasites, viruses and fungi. Viral diseases are highly infectious and capable of causing pandemics as evidenced by outbreaks of diseases like Ebola, Middle East Respiratory Syndrome, West Nile, SARS-Corona, Nipah, Hendra, Avian influenza and Swine influenza. EXPALANTION: Many viruses affecting equines are also important human pathogens. Diseases like Eastern equine encephalitis (EEE), Western equine encephalitis (WEE), and Venezuelan-equine encephalitis (VEE) are highly infectious and can be disseminated as aerosols. A large number of horses and human cases of VEE with fatal encephalitis have continuously occurred in Venezuela and Colombia. Vesicular stomatitis (VS) is prevalent in horses in North America and has zoonotic potential causing encephalitis in children. Hendra virus (HeV) causes respiratory and neurological disease and death in man and horses. Since its first outbreak in 1994, 53 disease incidents have been reported in Australia. West Nile fever has spread to many newer territories across continents during recent years. It has been described in Africa, Europe, South Asia, Oceania and North America. Japanese encephalitis has expanded horizons from Asia to western Pacific region including the eastern Indonesian archipelago, Papua New Guinea and Australia. Rabies is rare in horses but still a public health concern being a fatal disease. Equine influenza is historically not known to affect humans but many scientists have mixed opinions. Equine viral diseases of zoonotic importance and their impact on animal and human health have been elaborated in this article. CONCLUSION: Equine viral diseases though restricted to certain geographical areas have huge impact on equine and human health. Diseases like West Nile fever, Hendra, VS, VEE, EEE, JE, Rabies have the potential for spread and ability to cause disease in human. Equine influenza is historically not known to affect humans but some experimental and observational evidence show that H3N8 influenza virus has infected man. Despite our pursuit of understanding the complexity of the vector-host-pathogen mediating disease transmission, it is not possible to make generalized predictions concerning the degree of impact of disease emergence. A targeted, multidisciplinary effort is required to understand the risk factors for zoonosis and apply the interventions necessary to control it.",2018 Aug 31,"['Kumar, Balvinder', 'Manuja, Anju', 'Gulati, BR', 'Virmani, Nitin', 'Tripathi, B.N.']",Open Virol J,,,True
7d5f3ba38d99da2f79c4bd4ef3edbd8dfabc7cda,PMC,Molecular surveillance of respiratory viruses with bioaerosol sampling in an airport,http://dx.doi.org/10.1186/s40794-018-0071-7,PMC6142699,30237898,CC BY,"Recognizing that crowded, high-traffic airports and airplanes have been implicated in respiratory disease transmission, we partnered with administrators of Raleigh Durham International Airport (RDU) in conducting a pilot study of aerosol surveillance for respiratory viruses at RDU. From January to March 2018 we used NIOSH 2-stage samplers to collect 150 min aerosol samples in crowded areas at RDU. Four (17%) of the 24 samples were positive for known respiratory pathogens including influenza D virus and adenovirus. These results suggest the feasibility of employing bioaerosol surveillance techniques in public transportation areas, such as airports, as a noninvasive way to detect and characterize novel respiratory viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40794-018-0071-7) contains supplementary material, which is available to authorized users.",2018 Sep 17,"['Bailey, Emily S.', 'Choi, Jessica Y.', 'Zemke, Juliana', 'Yondon, Myagmarsukh', 'Gray, Gregory C.']",Trop Dis Travel Med Vaccines,,,True
0b137fde2327ae4665db6aef52d1c98fc4053864,PMC,Tips and Tricks for Validation of Quality Control Analytical Methods in Good Manufacturing Practice Mesenchymal Stromal Cell Production,http://dx.doi.org/10.1155/2018/3038565,PMC6142742,30254681,CC BY,"Mesenchymal stromal cells (MSC) for cellular therapy in European Union are classified as advanced therapy medicinal products (ATMPs), and their production must fulfill the requirements of Good Manufacturing Practice (GMP) rules. Despite their classification as medicinal products is already well recognized, there is still a lack of information and indications to validate methods and to adapt the noncompendial and compendial methods to these peculiar biological products with intrinsic characteristics that differentiate them from classic synthetic or biologic drugs. In the present paper, we present the results of the validation studies performed in the context of MSC development as ATMPs for clinical experimental use. Specifically, we describe the validation policies followed for sterility testing, endotoxins, adventitious viruses, cell count, and immunophenotyping. Our work demonstrates that it is possible to fully validate analytical methods also for ATMPs and that a risk-based approach can fill the gap between the prescription of the available guidelines shaped on traditional medicinal products and the peculiar characteristics of these novel and extremely promising new drugs.",2018 Sep 4,"['Viganò, Mariele', 'Budelli, Silvia', 'Lavazza, Cristiana', 'Montemurro, Tiziana', 'Montelatici, Elisa', 'de Cesare, Stefania', 'Lazzari, Lorenza', 'Orlandi, Anna Rosa', 'Lunghi, Giovanna', 'Giordano, Rosaria']",Stem Cells Int,,,True
b70b39df530a11f72c9e4a79b9aaaf4289a65c47,PMC,"Lessons from history: viral surveillance in 1940s East Africa: Epidemiological notes on some viruses isolated in Uganda, G. W. A. Dick, Transactions of the Royal Society of Tropical Medicine and Hygiene, 1953;47(1):13–48",http://dx.doi.org/10.1093/trstmh/try086,PMC6143150,30239943,CC BY,,2018 Sep 18,"['Carrington, Lauren B', 'Wills, Bridget']",Trans R Soc Trop Med Hyg,,,False
462c15b07dd915107b852ace8f6c49eb53fc9a9a,PMC,"Viral etiology of acute respiratory infections in hospitalized children in Novosibirsk City, Russia (2013 – 2017)",http://dx.doi.org/10.1371/journal.pone.0200117,PMC6143185,30226876,CC BY,"BACKGROUND: Acute respiratory infections (ARIs) cause a considerable morbidity and mortality worldwide especially in children. However, there are few studies of the etiological structure of ARIs in Russia. In this work, we analyzed the etiology of ARIs in children (0–15 years old) admitted to Novosibirsk Children’s Municipal Clinical Hospital in 2013–2017. METHODS: We tested nasal and throat swabs of 1560 children with upper or lower respiratory infection for main respiratory viruses (influenza viruses A and B, parainfluenza virus types 1–4, respiratory syncytial virus, metapneumovirus, four human coronaviruses, rhinovirus, adenovirus and bocavirus) using a RT-PCR Kit. RESULTS: We detected 1128 (72.3%) samples were positive for at least one virus. The most frequently detected pathogens were respiratory syncytial virus (358/1560, 23.0%), influenza virus (344/1560, 22.1%), and rhinovirus (235/1560, 15.1%). Viral co-infections were found in 163 out of the 1128 (14.5%) positive samples. We detected significant decrease of the respiratory syncytial virus-infection incidence in children with increasing age, while the reverse relationship was observed for influenza viruses. CONCLUSIONS: We evaluated the distribution of respiratory viruses in children with ARIs and showed the prevalence of respiratory syncytial virus and influenza virus in the etiological structure of infections. This study is important for the improvement and optimization of diagnostic tactics, control and prevention of the respiratory viral infections.",2018 Sep 18,"['Kurskaya, Olga', 'Ryabichenko, Tatyana', 'Leonova, Natalya', 'Shi, Weifeng', 'Bi, Hongtao', 'Sharshov, Kirill', 'Kazachkova, Eugenia', 'Sobolev, Ivan', 'Prokopyeva, Elena', 'Kartseva, Tatiana', 'Alekseev, Alexander', 'Shestopalov, Alexander']",PLoS One,,,True
33f569ebbee2a937504860dcfb7bb7801965f1f6,PMC,"Origin, Genetic Diversity, and Evolutionary Dynamics of Novel Porcine Circovirus 3",http://dx.doi.org/10.1002/advs.201800275,PMC6145280,30250786,CC BY,"Porcine circovirus 3 (PCV3) is a novel virus associated with acute PDNS (porcine dermatitis and nephropathy syndrome)‐like clinical signs identified by metagenomic sequencing from swine. Its high occurrence may pose a potential threat to the swine industry worldwide. The processes resulting in the emergence and spread of PCV3 remain poorly understood. Herein, the possible origin, genotypes, and evolutionary dynamics of PCV3 based on available genomic sequences are determined. The closest ancestor of PCV3 is found to be within the clade 1 bat CVs. Using different phylogenetic methods, two major genotypes are identified, PCV3a and PCV3b. It is found that the effective population size of PCV3 increased rapidly during late 2013 to early 2014 and this is associated with the diversification of PCV3a and PCV3b. A relatively high effective reproductive number (Re) value and higher evolutionary rate were found compared to other single‐stranded DNA viruses, and positive selection on codons 122 and 320 (24 of ORF2) is identified. It is hypothesized that this, together with the prediction of a potential change of an antigenic epitope at position 320, might have allowed PCV3 to escape from the host immune response. Overall, this study has important implications for understanding the ongoing PCV3 cases worldwide and will guide future efforts to develop effective preventive and control measures.",2018 Jul 4,"['Li, Gairu', 'He, Wanting', 'Zhu, Henan', 'Bi, Yuhai', 'Wang, Ruyi', 'Xing, Gang', 'Zhang, Cheng', 'Zhou, Jiyong', 'Yuen, Kwok‐Yung', 'Gao, George F.', 'Su, Shuo']",Adv Sci (Weinh),,,True
4cb6f55ffe1a352419056feaae3bd4e164ce2119,PMC,"Origin, Genetic Diversity, and Evolutionary Dynamics of Novel Porcine Circovirus 3",http://dx.doi.org/10.1002/advs.201800275,PMC6145280,30250786,CC BY,"Porcine circovirus 3 (PCV3) is a novel virus associated with acute PDNS (porcine dermatitis and nephropathy syndrome)‐like clinical signs identified by metagenomic sequencing from swine. Its high occurrence may pose a potential threat to the swine industry worldwide. The processes resulting in the emergence and spread of PCV3 remain poorly understood. Herein, the possible origin, genotypes, and evolutionary dynamics of PCV3 based on available genomic sequences are determined. The closest ancestor of PCV3 is found to be within the clade 1 bat CVs. Using different phylogenetic methods, two major genotypes are identified, PCV3a and PCV3b. It is found that the effective population size of PCV3 increased rapidly during late 2013 to early 2014 and this is associated with the diversification of PCV3a and PCV3b. A relatively high effective reproductive number (Re) value and higher evolutionary rate were found compared to other single‐stranded DNA viruses, and positive selection on codons 122 and 320 (24 of ORF2) is identified. It is hypothesized that this, together with the prediction of a potential change of an antigenic epitope at position 320, might have allowed PCV3 to escape from the host immune response. Overall, this study has important implications for understanding the ongoing PCV3 cases worldwide and will guide future efforts to develop effective preventive and control measures.",2018 Jul 4,"['Li, Gairu', 'He, Wanting', 'Zhu, Henan', 'Bi, Yuhai', 'Wang, Ruyi', 'Xing, Gang', 'Zhang, Cheng', 'Zhou, Jiyong', 'Yuen, Kwok‐Yung', 'Gao, George F.', 'Su, Shuo']",Adv Sci (Weinh),,,True
850be0ae2ae61513057e7b44b0b2e7b2f326746c,PMC,Best practices for standardized performance testing of infrared thermographs intended for fever screening,http://dx.doi.org/10.1371/journal.pone.0203302,PMC6145558,30231046,CC0,"Infrared (IR) modalities represent the only currently viable mass fever screening approaches for outbreaks of infectious disease pandemics such as Ebola virus disease and severe acute respiratory syndrome. Non-contact IR thermometers (NCITs) and IR thermographs (IRTs) have been used for fever screening in public areas such as airports. While NCITs remain a more popular choice than IRTs, there has been increasing evidences in the literature that IRTs can provide great accuracy in estimating body temperature if qualified systems are used and appropriate procedures are consistently applied. In this study, we addressed the issue of IRT qualification by implementing and evaluating a battery of test methods for objective, quantitative assessment of IRT performance based on a recent international standard (IEC 80601-2-59). We tested two commercial IRTs to evaluate their stability and drift, image uniformity, minimum resolvable temperature difference, and radiometric temperature laboratory accuracy. Based on these tests, we illustrated how experimental and data processing procedures could affect results, and suggested methods for clarifying and optimizing test methods. Overall, the insights into thermograph standardization and acquisition methods provided by this study may improve the utility of IR thermography and aid in comparing IRT performance, thus improving the potential for producing high quality disease pandemic countermeasures.",2018 Sep 19,"['Ghassemi, Pejman', 'Pfefer, T. Joshua', 'Casamento, Jon P.', 'Simpson, Rob', 'Wang, Quanzeng']",PLoS One,,,True
37dcd4f6316a14205dd4887216b931a3877a0f50,PMC,An alternative pathway of enteric PEDV dissemination from nasal cavity to intestinal mucosa in swine,http://dx.doi.org/10.1038/s41467-018-06056-w,PMC6145876,30232333,CC BY,"Porcine epidemic diarrhea virus (PEDV) has catastrophic impacts on the global pig industry. Although the fecal–oral route is generally accepted, an increased number of reports indicate that airborne transmission may contribute to PEDV outbreak. Here, we show that PEDV could cause typical diarrhea in piglets through a nasal spray. Firstly, PEDV can develop a transient nasal epithelium infection. Subsequently, PEDV-carrying dendritic cells (DCs) allow the virus to be transferred to CD3(+) T cells via the virological synapse. Finally, virus-loaded CD3(+) T cells reach the intestine through the blood circulation, leading to intestinal infection via cell-to-cell contact. Our study provides evidence for airborne transmission of a gastrointestinal infected coronavirus and illustrates the mechanism of its transport from the entry site to the pathogenic site.",2018 Sep 19,"['Li, Yuchen', 'Wu, Qingxin', 'Huang, Lulu', 'Yuan, Chen', 'Wang, Jialu', 'Yang, Qian']",Nat Commun,,,True
77f0ea2c96326d37a9a2a71d529fe7c29336f6ee,PMC,An alternative pathway of enteric PEDV dissemination from nasal cavity to intestinal mucosa in swine,http://dx.doi.org/10.1038/s41467-018-06056-w,PMC6145876,30232333,CC BY,"Porcine epidemic diarrhea virus (PEDV) has catastrophic impacts on the global pig industry. Although the fecal–oral route is generally accepted, an increased number of reports indicate that airborne transmission may contribute to PEDV outbreak. Here, we show that PEDV could cause typical diarrhea in piglets through a nasal spray. Firstly, PEDV can develop a transient nasal epithelium infection. Subsequently, PEDV-carrying dendritic cells (DCs) allow the virus to be transferred to CD3(+) T cells via the virological synapse. Finally, virus-loaded CD3(+) T cells reach the intestine through the blood circulation, leading to intestinal infection via cell-to-cell contact. Our study provides evidence for airborne transmission of a gastrointestinal infected coronavirus and illustrates the mechanism of its transport from the entry site to the pathogenic site.",2018 Sep 19,"['Li, Yuchen', 'Wu, Qingxin', 'Huang, Lulu', 'Yuan, Chen', 'Wang, Jialu', 'Yang, Qian']",Nat Commun,,,True
0d9a4673c7ff4a10e5e84667278b2fa3f8ac729f,PMC,Detection of Novel duck reovirus (NDRV) using visual reverse transcription loop-mediated isothermal amplification (RT-LAMP),http://dx.doi.org/10.1038/s41598-018-32473-4,PMC6145877,30232402,CC BY,"Here we present a visual reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for detecting the gene encoding the σB major outer-capsid protein of novel duck reovirus (NDRV). A set of primers, composed of two outer primers, two inner primers and two loop primers, was designed based on the gene of interest. The LAMP reaction was conducted in a traditional laboratory water bath at 65 °C for 50 min. We compared the performance of calcein/Mn(2+) and SYBR Green I dyes, as well as electrophoresis on agarose gel stained with GoldView nucleic acid dye to detect the RT-LAMP-amplified products and all assays could be employed to discriminate between positive and negative specimens in visible or UV light. Our data showed that there is no cross-reaction with other viruses and the RT-LAMP technique displayed high sensitivity for detecting NDRV with a minimal detection limit of 200 fg RNA input. This assay was more sensitive than conventional PCR in detecting NDRV both in natural and experimental infection. In conclusion, the RT-LAMP technique was remarkably sensitive, specific, rapid, simple and profitable for the identification of NDRV.",2018 Sep 19,"['Li, Zhili', 'Cai, Yuejia', 'Liang, Guozhi', 'El-Ashram, Saeed', 'Mei, Minmin', 'Huang, Wenjing', 'Li, Xiaowen', 'Li, Wenfeng', 'He, Cheng', 'Huang, Shujian']",Sci Rep,,,False
9728dc7174668523338b32a9608f43a91e8b797d,PMC,Detection of Novel duck reovirus (NDRV) using visual reverse transcription loop-mediated isothermal amplification (RT-LAMP),http://dx.doi.org/10.1038/s41598-018-32473-4,PMC6145877,30232402,CC BY,"Here we present a visual reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for detecting the gene encoding the σB major outer-capsid protein of novel duck reovirus (NDRV). A set of primers, composed of two outer primers, two inner primers and two loop primers, was designed based on the gene of interest. The LAMP reaction was conducted in a traditional laboratory water bath at 65 °C for 50 min. We compared the performance of calcein/Mn(2+) and SYBR Green I dyes, as well as electrophoresis on agarose gel stained with GoldView nucleic acid dye to detect the RT-LAMP-amplified products and all assays could be employed to discriminate between positive and negative specimens in visible or UV light. Our data showed that there is no cross-reaction with other viruses and the RT-LAMP technique displayed high sensitivity for detecting NDRV with a minimal detection limit of 200 fg RNA input. This assay was more sensitive than conventional PCR in detecting NDRV both in natural and experimental infection. In conclusion, the RT-LAMP technique was remarkably sensitive, specific, rapid, simple and profitable for the identification of NDRV.",2018 Sep 19,"['Li, Zhili', 'Cai, Yuejia', 'Liang, Guozhi', 'El-Ashram, Saeed', 'Mei, Minmin', 'Huang, Wenjing', 'Li, Xiaowen', 'Li, Wenfeng', 'He, Cheng', 'Huang, Shujian']",Sci Rep,,,True
69dfbde6c5ed2f0c93261cf763e206f0f3d63132,PMC,A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV,http://dx.doi.org/10.1128/JVI.00837-18,PMC6146697,29950421,CC BY,"The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) continues to infect humans and camels, calling for efficient, cost-effective, and broad-spectrum strategies to control its spread. Nanobodies (Nbs) are single-domain antibodies derived from camelids and sharks and are potentially cost-effective antivirals with small size and great expression yield. In this study, we developed a novel neutralizing Nb (NbMS10) and its human-Fc-fused version (NbMS10-Fc), both of which target the MERS-CoV spike protein receptor-binding domain (RBD). We further tested their receptor-binding affinity, recognizing epitopes, cross-neutralizing activity, half-life, and efficacy against MERS-CoV infection. Both Nbs can be expressed in yeasts with high yield, bind to MERS-CoV RBD with high affinity, and block the binding of MERS-CoV RBD to the MERS-CoV receptor. The binding site of the Nbs on the RBD was mapped to be around residue Asp539, which is part of a conserved conformational epitope at the receptor-binding interface. NbMS10 and NbMS10-Fc maintained strong cross-neutralizing activity against divergent MERS-CoV strains isolated from humans and camels. Particularly, NbMS10-Fc had significantly extended half-life in vivo; a single-dose treatment of NbMS10-Fc exhibited high prophylactic and therapeutic efficacy by completely protecting humanized mice from lethal MERS-CoV challenge. Overall, this study proves the feasibility of producing cost-effective, potent, and broad-spectrum Nbs against MERS-CoV and has produced Nbs with great potentials as anti-MERS-CoV therapeutics. IMPORTANCE Therapeutic development is critical for preventing and treating continual MERS-CoV infections in humans and camels. Because of their small size, nanobodies (Nbs) have advantages as antiviral therapeutics (e.g., high expression yield and robustness for storage and transportation) and also potential limitations (e.g., low antigen-binding affinity and fast renal clearance). Here, we have developed novel Nbs that specifically target the receptor-binding domain (RBD) of MERS-CoV spike protein. They bind to a conserved site on MERS-CoV RBD with high affinity, blocking RBD's binding to MERS-CoV receptor. Through engineering a C-terminal human Fc tag, the in vivo half-life of the Nbs is significantly extended. Moreover, the Nbs can potently cross-neutralize the infections of diverse MERS-CoV strains isolated from humans and camels. The Fc-tagged Nb also completely protects humanized mice from lethal MERS-CoV challenge. Taken together, our study has discovered novel Nbs that hold promise as potent, cost-effective, and broad-spectrum anti-MERS-CoV therapeutic agents.",2018 Aug 29,"['Zhao, Guangyu', 'He, Lei', 'Sun, Shihui', 'Qiu, Hongjie', 'Tai, Wanbo', 'Chen, Jiawei', 'Li, Jiangfan', 'Chen, Yuehong', 'Guo, Yan', 'Wang, Yufei', 'Shang, Jian', 'Ji, Kaiyuan', 'Fan, Ruiwen', 'Du, Enqi', 'Jiang, Shibo', 'Li, Fang', 'Du, Lanying', 'Zhou, Yusen']",J Virol,,,True
b77ed891047029cda65117192670f81edf87f1dd,PMC,The S2 Subunit of Infectious Bronchitis Virus Beaudette Is a Determinant of Cellular Tropism,http://dx.doi.org/10.1128/JVI.01044-18,PMC6146808,30021894,CC BY,"The spike (S) glycoprotein of the avian gammacoronavirus infectious bronchitis virus (IBV) is comprised of two subunits (S1 and S2), has a role in virulence in vivo, and is responsible for cellular tropism in vitro. We have previously demonstrated that replacement of the S glycoprotein ectodomain from the avirulent Beaudette strain of IBV with the corresponding region from the virulent M41-CK strain resulted in a recombinant virus, BeauR-M41(S), with the in vitro cell tropism of M41-CK. The IBV Beaudette strain is able to replicate in both primary chick kidney cells and Vero cells, whereas the IBV M41-CK strain replicates in primary cells only. In order to investigate the region of the IBV S responsible for growth in Vero cells, we generated a series of recombinant IBVs expressing chimeric S glycoproteins, consisting of regions from the Beaudette and M41-CK S gene sequences, within the genomic background of Beaudette. The S2, but not the S1, subunit of the Beaudette S was found to confer the ability to grow in Vero cells. Various combinations of Beaudette-specific amino acids were introduced into the S2 subunit of M41 to determine the minimum requirement to confer tropism for growth in Vero cells. The ability of IBV to grow and produce infectious progeny virus in Vero cells was subsequently narrowed down to just 3 amino acids surrounding the S2′ cleavage site. Conversely, swapping of the 3 Beaudette-associated amino acids with the corresponding ones from M41 was sufficient to abolish Beaudette growth in Vero cells. IMPORTANCE Infectious bronchitis remains a major problem in the global poultry industry, despite the existence of many different vaccines. IBV vaccines, both live attenuated and inactivated, are currently grown on embryonated hen's eggs, a cumbersome and expensive process due to the fact that most IBV strains do not grow in cultured cells. The reverse genetics system for IBV creates the opportunity for generating rationally designed and more effective vaccines. The observation that IBV Beaudette has the additional tropism for growth on Vero cells also invokes the possibility of generating IBV vaccines produced from cultured cells rather than by the use of embryonated eggs. The regions of the IBV Beaudette S glycoprotein involved in the determination of extended cellular tropism were identified in this study. This information will enable the rational design of a future generation of IBV vaccines that may be grown on Vero cells.",2018 Sep 12,"['Bickerton, Erica', 'Maier, Helena J.', 'Stevenson-Leggett, Phoebe', 'Armesto, Maria', 'Britton, Paul']",J Virol,,,True
9016b018eebc8b664e98f9ff2cd6f05ea1742dc7,PMC,Bats Are an Untapped System for Understanding Microbiome Evolution in Mammals,http://dx.doi.org/10.1128/mSphere.00397-18,PMC6147128,30232167,CC BY,"Mammals evolved in a microbial world, and consequently, microbial symbionts have played a role in their evolution. An exciting new subdiscipline of metagenomics considers the ways in which microbes, particularly those found in the gut, have facilitated the ecological and phylogenetic radiation of mammals. However, the vast majority of such studies focus on domestic animals, laboratory models, or charismatic megafauna (e.g., pandas and chimpanzees). The result is a plethora of studies covering few taxa across the mammal tree of life, leaving broad patterns of microbiome function and evolution unclear. Wildlife microbiome research urgently needs a model system in which to test hypotheses about metagenomic involvement in host ecology and evolution. We propose that bats (Order: Chiroptera) represent a model system ideal for comparative microbiome research, affording opportunities to examine host phylogeny, diet, and other natural history characteristics in relation to the evolution of the gut microbiome.",2018 Sep 19,"['Ingala, Melissa R.', 'Simmons, Nancy B.', 'Perkins, Susan L.']",mSphere,,,True
ca96c55394d856036b970cb39c695ef3bb616454,PMC,Report from the Medical Library Association’s InSight Initiative Summit 1: Engaging Users in a Disruptive Era,http://dx.doi.org/10.5195/jmla.2018.561,PMC6148620,30271306,CC BY,"At the Medical Library Association’s Insight Initiative Summit 1, held March 6–7, 2018, academic and hospital librarians and publishing industry partners came together to discuss their shared role in engaging users of health sciences information in an era in which “disruptors” such as pirate websites, scientific collaboration networks, and preprint servers pose threats to traditional means of access to scholarly content. Through a mixture of keynote talks, themed panel discussions, and small-group problem-solving exercises, the summit program raised important questions, sparked conversation, and provided insight into the need for both libraries and publishing organizations to improve their user experience, lower their barriers to access, and offer value to users that cannot be provided by competitors, including helping authors and students become informed, responsible advocates for and consumers of scholarly publications. The key takeaways from the summit are expected to impact libraries’ and publishers’ strategies and stimulate the cocreation of enduring materials to enhance user engagement in disseminating and discovering scientific and medical information.",2018 Oct 1,"Akers, Katherine G.",J Med Libr Assoc,,,True
00623bf2715e25d3acacb3f210d6888ed840e3cb,PMC,Transmissible gastroenteritis virus infection decreases arginine uptake by downregulating CAT-1 expression,http://dx.doi.org/10.1186/s13567-018-0591-1,PMC6148772,30236161,CC BY,"Transmissible gastroenteritis virus (TGEV) is a coronavirus that causes severe diarrhea in suckling piglets. TGEV primarily targets and infects porcine intestinal epithelial cells, which play an important role in nutrient absorption. However, the effects of TGEV infection on nutrient absorption in swine have not yet been investigated. In this study, we evaluated the impact of TGEV infection on arginine uptake using the porcine small intestinal epithelial cell line IPEC-J2 as a model system. High performance liquid chromatography (HPLC) analyses showed that TGEV infection leads to reduced arginine uptake at 48 hours post-infection (hpi). Expression of cationic amino acid transporter 1 (CAT-1) was attenuated as well. TGEV infection induced activation of phospho-protein kinase C α (p-PKC α), phospho-epidermal growth factor receptor (p-EGFR), and enhanced the expression of caveolin-1, all of which appear to be involved in down-regulating arginine uptake and CAT-1 expression. These results illuminate the relationship between TGEV infection and nutrient absorption, and further our understanding of the mechanisms of TGEV infection.",2018 Sep 20,"['Xia, Lu', 'Dai, Lei', 'Yang, Qian']",Vet Res,,,True
d8ec38752ec638efa9b55dffa8d0277ce889c976,PMC,Pathobiology of Avian avulavirus 1: special focus on waterfowl,http://dx.doi.org/10.1186/s13567-018-0587-x,PMC6148804,30231933,CC BY,"Avian avulaviruses serotype 1 (abbreviated as APMV-1 for the historical name avian paramyxovirus 1) are capable of infecting a wide spectrum of avian species with variable clinical symptoms and outcomes. Ease of transmission has allowed the virus to spread worldwide with varying degrees of virulence depending upon the virus strain and host species. The emergence of new virulent genotypes from global epizootics, and the year-to-year genomic changes in low and high virulence APMV-1 imply that distinct genotypes of APMV-1 are simultaneously evolving at different geographic locations across the globe. This vast genomic diversity may be favoured by large variety of avian species susceptibility to APMV-1 infection, and by the availability of highly mobile wild birds. It has long been considered that waterfowls are not sensitive to APMV-1 and are unable to show any clinical signs, however, outbreaks from the 90′s contradict these concepts. The APMV-1 isolates are increasingly reported from the waterfowl. Waterfowl have strong innate immune responses, which minimize the impact of virus infection, however, are unable to prevent the viral shedding. Numerous APMV-1 are carried by domestic waterfowl intermingling with terrestrial poultry. Therefore, commercial ducks and geese should be vaccinated against APMV-1 to minimize the virus shedding and for the prevention the transmission. Genetic diversity within APMV-1 demonstrates the need for continual monitoring of viral evolution and periodic updates of vaccine seed-strains to achieve efficient control and eradication of APMV-1 in waterfowls. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13567-018-0587-x) contains supplementary material, which is available to authorized users.",2018 Sep 19,"['Rehman, Zaib Ur.', 'Meng, Chunchun', 'Sun, Yingjie', 'Mahrose, Khalid M.', 'Umar, Sajid', 'Ding, Chan', 'Munir, Muhammad']",Vet Res,,,True
d7b6798207f4093ed2187fc0d159bdb21a979f0b,PMC,"IFITM1 expression is crucial to gammaherpesvirus infection, in vivo",http://dx.doi.org/10.1038/s41598-018-32350-0,PMC6149222,30237526,CC BY,"The oncogenic gammaherpesviruses, Epstein–Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV), are etiologically associated with a variety of human cancers, including Burkitt’s lymphoma (BL), Hodgkin lymphoma (HL), Kaposi’s sarcoma (KS), and primary effusion lymphoma (PEL). Recently, we demonstrated KSHV infection of B- and endothelial cells to significantly upregulate the expression of interferon induced transmembrane protein 1 (IFITM1) which in turn enhances virus entry. This is an extension of the above study. In here, we determined EBV infection of cells to trigger IFITM1 expression, in vitro. Silencing IFITM1 expression using siRNA specifically lowered gammaherpesvirus infection of cells at a post binding stage of entry. A natural model system to explore the effect of IFITM1 on gammaherpesvirus infection in vivo is infection of BALB/c mice with murine gammaherpesvirus 68 (MHV-68). Priming mice with siRNA specific to IFITM1 significantly lowered MHV-68 titers in the lung specimens compared to priming with (NS)siRNA or PBS. MHV-68 titers were monitored by plaque assay and qPCR. Taken together, for the first time, this study provides insight into the critical role of IFITM1 to promoting in vivo gammaherpesvirus infections.",2018 Sep 20,"['Hussein, Hosni A. M.', 'Briestenska, Katarina', 'Mistrikova, Jela', 'Akula, Shaw M.']",Sci Rep,,,True
506764ffd8140a103b330aa1dbb12d4b921ffda2,PMC,Development of a sensitive and specific xMAP assay for detection of antibodies against infectious laryngotracheitis and bronchitis viruses,http://dx.doi.org/10.1186/s12985-018-1048-x,PMC6151043,30241540,CC BY,"BACKGROUND: A serological method to simultaneously detect antibodies against infectious laryngotracheitis virus (ILTV) and infectious bronchitis virus (IBV) is imperative for the differential diagnosis and evaluation of antibodies titers after vaccination. METHOD: The microspheres coated with purified recombinant glycoprotein D (gD) of ILTV or nucleocapsid (N) protein of IBV were incubated with serum samples. The simultaneous quantification of ILTV and IBV antibodies were achieved through the interrogation of microspheres by Luminex 200 detection system. . RESULTS: This xMAP detection demonstrated no nonspecific reactions with avian influenza virus (AIV), avian leukosis virus (ALV), newcastle disease virus (NDV), and Marek’s disease virus (MDV). The results also demonstrated that the xMAP assay was four times more sensitive than the enzyme-linked immunosorbent assay (ELISA) for ILTV detection and two times more sensitive for IBV detection. A total of 90 chicken serum samples from a chicken farm were tested by xMAP and ELISA assays. The results showed that the coincidence rates were 84.44 and 100% for ILTV and IBV detection, respectively. CONCLUSION: This study exhibited an opportunity for the differential diagnosis through simultaneous detection of multiplex antibodies in serum and can be used for the multiplex antibodies evaluation after vaccination.",2018 Sep 21,"['Wang, Huanan', 'Cong, Feng', 'Guan, Jianchi', 'Xiao, Li', 'Zhu, Yujun', 'Lian, Yuexiao', 'Huang, Ren', 'Chen, Meili', 'Guo, Pengju']",Virol J,,,True
6ee9f517e7b70ca8149459475ea4de6095c46f26,PMC,"The Genus Alnus, A Comprehensive Outline of Its Chemical Constituents and Biological Activities",http://dx.doi.org/10.3390/molecules22081383,PMC6152317,28825681,CC BY,"The genus Alnus (Betulaceae) is comprised of more than 40 species. Many species of this genus have a long history of use in folk medicines. Phytochemical investigations have revealed the presence of diarylheptanoids, polyphenols, flavonoids, terpenoids, steroids and other compounds. Diarylheptanoids, natural products with a 1,7-diphenylheptane structural skeleton, are the dominant constituents in the genus, whose anticancer effect has been brought into focus. Pure compounds and crude extracts from the genus exhibit a wide spectrum of pharmacological activities both in vitro and in vivo. This paper compiles 273 naturally occurring compounds from the genus Alnus along with their structures and pharmacological activities, as reported in 138 references.",2017 Aug 21,"['Ren, Xueyang', 'He, Ting', 'Chang, Yanli', 'Zhao, Yicheng', 'Chen, Xiaoyi', 'Bai, Shaojuan', 'Wang, Le', 'Shen, Meng', 'She, Gaimei']",Molecules,,,True
0dbfaa6ddc08bef9b502de5cd6c0a2a3b7af0106,PMC,One Group's Historical Reflections on DNA Vaccine Development,http://dx.doi.org/10.1089/hum.2018.066,PMC6152846,30129778,CC BY,"DNA vaccines were pioneered by several groups in the early 1990s. This article presents the reflections of one of these groups on their work with retroviral vectors in chickens that contributed to the discovery and early development of DNA vaccines. Although the findings were initially met with skepticism, the work presented here combined with that of others founded a new method of vaccination: the direct inoculation of purified DNA encoding the target antigen.",2018 Sep 1,"['Fynan, Ellen F.', 'Lu, Shan', 'Robinson, Harriet L.']",Hum Gene Ther,,,True
05da888d78a628666b186a2f0773d8d4839a994e,PMC,"Burden of exposure to infectious bursal disease virus, infectious bronchitis virus, Newcastle disease virus, Mycoplasma gallisepticum, and intestinal parasites in introduced broiler chickens on the Galapagos",http://dx.doi.org/10.1371/journal.pone.0203658,PMC6152864,30248128,CC BY,"Diseases in introduced broilers can possibly spill over to wild birds on the Galapagos. Knowledge about the current burden of exposure to pathogens in broilers on the Galapagos is very limited. The objective of the study reported here was to measure the burden of exposure to infectious bursal disease virus (IBDV), infectious bronchitis virus (IBV), Newcastle disease virus (NDV), Mycoplasma gallisepticum (MG), and intestinal parasites in a sample of broiler chickens on 13 farms on Santa Cruz Island and San Cristobal Island in July 2017. Blood serum samples were tested for detection of antibodies to IBDV, IBV, NDV, and MG by using an IDEXX Enzyme-linked Immunosorbent Assay. In addition, fecal samples and pen bedding environmental samples were processed and analyzed for diagnosis of intestinal parasite eggs under a compound light microscope. The frequency of seropositive broilers to IBDV was 74/130 or 56% (95% CI = 48, 65%), to IBV was 27/130 or 20% (14, 28%), and to NDV was 1/130 or 0.7% (0.1, 4%). All broilers tested negative to MG antibodies. Eimeria spp. infection was common in study broilers. Finally, we observed interaction between broiler chickens and wild birds (finches) inside broiler pens, as well as the presence of backyard chickens inside property limits of study farms. This study produced evidence that exposure to IBDV, IBV, and intestinal parasites in broilers on Santa Cruz Island and San Cristobal Island is important. Study results are relevant because (i) they provide new baseline data on the burden of exposure to avian pathogens in broiler farms, (ii) justify the need to verify standard operating procedures in hatcheries that supply (non-vaccinated) day-old chicks to the Galapagos and (iii) to implement enhanced biosecurity standards on broiler chicken farms to mitigate risk of disease transmission between broilers, backyard poultry, and wild birds on the Galapagos.",2018 Sep 24,"['Whitehead, Ashley B. R.', 'Butcher, Gary D.', 'Walden, Heather S.', 'Duque, Viviana', 'Cruz, Marilyn', 'Hernandez, Jorge A.']",PLoS One,,,True
4bc6d312effedb4dafb7bca22236c006ad1f7136,PMC,"Estimating human-to-human transmissibility of hepatitis A virus in an outbreak at an elementary school in China, 2011",http://dx.doi.org/10.1371/journal.pone.0204201,PMC6152969,30248120,CC BY,"Hepatitis A is caused by hepatitis A virus and occurs worldwide. Estimating the transmissibility, which is usually characterized by the basic reproductive number R(0), the mean number of secondary infectious cases generated by a single primary infectious case introduced into a totally susceptible population, provides crucial information for the effort required to stop infection spreading. Hepatitis A virus is usually transmitted indirectly through contaminated food and environment. An outbreak from March to June 2011 was reported to have occurred at an elementary school of 698 pupils in China and it was found that the outbreak was due to direct transmission between school children. Based on the symptom onset date and the social contact network of the children, in this study we estimate the serial interval (i.e. the gap in symptom onset between an infectee and its infector) and use different statistical methods to estimate R(0). Combining with the positivity of IgG antibodies tests, we develop a compartmental transmission dynamics model which includes both asymptomatic and symptomatic infections to estimate the overall R(0). Our analysis suggests a serial interval of mean = 23.9 days and standard deviation = 20.9 days. The different statistical methods suggest estimates for R(0) in the outbreak varying from 2.1 to 2.8, and the estimates from the transmission dynamics model are consistent with this range. Our estimates are in agreement with that from one study in England but are higher than that from one study in the United States. Our transmission dynamics model suggests that the proportion of symptomatic infections is about 9%, implying that there were about 344 asymptomatic infections along with the 32 observed symptomatic cases. Furthermore, it is shown that the inclusion of asymptomatic infection in the epidemic process increases the estimate of R(0) but does not do so greatly provided that the proportion of symptomatic infections is constant over the outbreak and there is no difference in transmissibility between symptomatic and asymptomatic infections.",2018 Sep 24,"['Zhang, Xu-Sheng', 'Iacono, Giovanni Lo']",PLoS One,,,True
4013a7e351c40d2bb7fdfe7f185d2ef9b1a872e6,PMC,Viral Sepsis in Children,http://dx.doi.org/10.3389/fped.2018.00252,PMC6153324,30280095,CC BY,"Sepsis in children is typically presumed to be bacterial in origin until proven otherwise, but frequently bacterial cultures ultimately return negative. Although viruses may be important causative agents of culture-negative sepsis worldwide, the incidence, disease burden and mortality of viral-induced sepsis is poorly elucidated. Consideration of viral sepsis is critical as its recognition carries implications on appropriate use of antibacterial agents, infection control measures, and, in some cases, specific, time-sensitive antiviral therapies. This review outlines our current understanding of viral sepsis in children and addresses its epidemiology and pathophysiology, including pathogen-host interaction during active infection. Clinical manifestation, diagnostic testing, and management options unique to viral infections will be outlined.",2018 Sep 18,"['Gupta, Neha', 'Richter, Robert', 'Robert, Stephen', 'Kong, Michele']",Front Pediatr,,,True
a6d3a75a05c35723193e5240b3ebd2a01a77f4d2,PMC,First retrospective studies with etiological confirmation of porcine transmissible gastroenteritis virus infection in Argentina,http://dx.doi.org/10.1186/s12917-018-1615-9,PMC6154422,30249258,CC BY,"BACKGROUND: In 2014, a notification of porcine transmissible gastroenteritis virus (TGEV) was made by the National Services of Animal Health of Argentina (SENASA) to the World Organization of Animal Health (OIE). The notification was based on a serological diagnosis in a small farm with a morbidity rate of 2.3% without enteric clinical signs. In order to determine if TGEV was circulating before the official report, a retrospective study on cases of neonatal diarrhea was performed. The selection criteria was a sudden increase in mortality in 1- to 21-day-old piglets with watery diarrhea that did not respond to antibiotics. Based on these criteria, three clinical cases were identified during 2010–2015. RESULTS: All animals that were evaluated presented histological lesions consistent with enteric viral infection. The feces and ultrathin sections of intestine that were evaluated by electron microscopy confirmed the presence of round particles of approximately 80 nm in size and characterized by finely granular electrodense nucleoids consistent with complete particles of coronavirus. The presence of the TGEV antigen was confirmed by monoclonal specific immunohistochemistry, and final confirmation of a metabolically-active virus was performed by in situ hybridization to detect a TGE mRNA encoding spike protein. All sections evaluated in this case were negative for PEDV and rotavirus A. CONCLUSIONS: This is the first case series describing neonatal mortality with etiological confirmation of TGEV in Argentina. The clinical diagnosis of TGEV infections in endemic regions is challenging due to the epidemiological distribution and coinfection with other enteric pathogens that mask the clinical presentation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1615-9) contains supplementary material, which is available to authorized users.",2018 Sep 24,"['Piñeyro, Pablo Enrique', 'Lozada, Maria Inez', 'Alarcón, Laura Valeria', 'Sanguinetti, Ramon', 'Cappuccio, Javier Alejandro', 'Pérez, Estefanía Marisol', 'Vannucci, Fabio', 'Armocida, Alberto', 'Madson, Darin Michael', 'Perfumo, Carlos Juan', 'Quiroga, Maria Alejandra']",BMC Vet Res,,,True
2e27f1de90668d3c54ffb49720a9a978383cc78b,PMC,Applications of Gold Nanoparticles in Nanomedicine: Recent Advances in Vaccines †,http://dx.doi.org/10.3390/molecules22050857,PMC6154615,28531163,CC BY,"Nowadays, gold is used in (nano-)medicine, usually in the form of nanoparticles, due to the solid proofs given of its therapeutic effects on several diseases. Gold also plays an important role in the vaccine field as an adjuvant and a carrier, reducing toxicity, enhancing immunogenic activity, and providing stability in storage. An even brighter golden future is expected for gold applications in this area.",2017 May 22,"Carabineiro, Sónia Alexandra Correia",Molecules,,,True
e1c5d3a82f4296f2867ccca63989530f17a773d7,PMC,Using UPLC-MS/MS for Characterization of Active Components in Extracts of Yupingfeng and Application to a Comparative Pharmacokinetic Study in Rat Plasma after Oral Administration,http://dx.doi.org/10.3390/molecules22050810,PMC6154636,28513568,CC BY,"Yupingfeng (YPF), a famous traditional Chinese medicine, which contains a large array of compounds, has been effectually used in health protection. A two-dimensional liquid chromatography ((2)D-LC) combined with quadrupole time-of-flight mass spectrometry (QTOF-MS) method was firstly established to separate and identify chemical components in YPF. A total of 33 compounds were identified, including 15 constituents (flavonoids and saponins) in Astragali radix; seven constituents (sesquiterpenoids and polysaccharide) in Atractylodis rhizoma; and 11 constituents (chromone and coumarins) in Saposhnikoviae radix. The corresponding fragmentation pathway of typical substances was investigated. Then, seven active constituents (astragaloside, calycosin, formononetin, cimicifugoside, 4-O-beta-d-glucosyl-5-O-methylvisamminol, sec-O-glucosylhamaudol, and atractylenolide II) derived from three medicinal plants were chosen to further investigate the pharmacokinetic behavior of YPF formula using ultrahigh-performance liquid chromatography with triple quadrupole mass spectrometry system. The method was sensitive, accurate and reliable. We also used the area under the plasma concentration–time curve from zero to infinity (AUC(0−∞)) as weighting factor to make an integrated pharmacokinetic curve. Results show that the constituents of Saposhnikoviae radix have the best absorption and pharmacokinetic behavior and may play important role in leading to the changes of overall therapeutic effects of YPF. Further study is needed to confirm the association between them.",2017 May 17,"['Jia, Meng-Qi', 'Xiong, Ye-Juan', 'Xue, Yun', 'Wang, Yan', 'Yan, Chao']",Molecules,,,True
7acb08acf019dcfc8817e3cb58306e6b37b969ab,PMC,Using UPLC-MS/MS for Characterization of Active Components in Extracts of Yupingfeng and Application to a Comparative Pharmacokinetic Study in Rat Plasma after Oral Administration,http://dx.doi.org/10.3390/molecules22050810,PMC6154636,28513568,CC BY,"Yupingfeng (YPF), a famous traditional Chinese medicine, which contains a large array of compounds, has been effectually used in health protection. A two-dimensional liquid chromatography ((2)D-LC) combined with quadrupole time-of-flight mass spectrometry (QTOF-MS) method was firstly established to separate and identify chemical components in YPF. A total of 33 compounds were identified, including 15 constituents (flavonoids and saponins) in Astragali radix; seven constituents (sesquiterpenoids and polysaccharide) in Atractylodis rhizoma; and 11 constituents (chromone and coumarins) in Saposhnikoviae radix. The corresponding fragmentation pathway of typical substances was investigated. Then, seven active constituents (astragaloside, calycosin, formononetin, cimicifugoside, 4-O-beta-d-glucosyl-5-O-methylvisamminol, sec-O-glucosylhamaudol, and atractylenolide II) derived from three medicinal plants were chosen to further investigate the pharmacokinetic behavior of YPF formula using ultrahigh-performance liquid chromatography with triple quadrupole mass spectrometry system. The method was sensitive, accurate and reliable. We also used the area under the plasma concentration–time curve from zero to infinity (AUC(0−∞)) as weighting factor to make an integrated pharmacokinetic curve. Results show that the constituents of Saposhnikoviae radix have the best absorption and pharmacokinetic behavior and may play important role in leading to the changes of overall therapeutic effects of YPF. Further study is needed to confirm the association between them.",2017 May 17,"['Jia, Meng-Qi', 'Xiong, Ye-Juan', 'Xue, Yun', 'Wang, Yan', 'Yan, Chao']",Molecules,,,False
61a0959ae057e4e5522e34c794fc731ca5a762ee,PMC,"Loperamide, pimozide, and STF-62247 trigger autophagy-dependent cell death in glioblastoma cells",http://dx.doi.org/10.1038/s41419-018-1003-1,PMC6155211,30250198,CC BY,"Autophagy is a well-described degradation mechanism that promotes cell survival upon nutrient starvation and other forms of cellular stresses. In addition, there is growing evidence showing that autophagy can exert a lethal function via autophagic cell death (ACD). As ACD has been implicated in apoptosis-resistant glioblastoma (GBM), there is a high medical need for identifying novel ACD-inducing drugs. Therefore, we screened a library containing 70 autophagy-inducing compounds to induce ATG5-dependent cell death in human MZ-54 GBM cells. Here, we identified three compounds, i.e. loperamide, pimozide, and STF-62247 that significantly induce cell death in several GBM cell lines compared to CRISPR/Cas9-generated ATG5- or ATG7-deficient cells, pointing to a death-promoting role of autophagy. Further cell death analyses conducted using pharmacological inhibitors revealed that apoptosis, ferroptosis, and necroptosis only play minor roles in loperamide-, pimozide- or STF-62247-induced cell death. Intriguingly, these three compounds induce massive lipidation of the autophagy marker protein LC3B as well as the formation of LC3B puncta, which are characteristic of autophagy. Furthermore, loperamide, pimozide, and STF-62247 enhance the autophagic flux in parental MZ-54 cells, but not in ATG5 or ATG7 knockout (KO) MZ-54 cells. In addition, loperamide- and pimozide-treated cells display a massive formation of autophagosomes and autolysosomes at the ultrastructural level. Finally, stimulation of autophagy by all three compounds is accompanied by dephosphorylation of mammalian target of rapamycin complex 1 (mTORC1), a well-known negative regulator of autophagy. In summary, our results indicate that loperamide, pimozide, and STF-62247 induce ATG5- and ATG7-dependent cell death in GBM cells, which is preceded by a massive induction of autophagy. These findings emphasize the lethal function and potential clinical relevance of hyperactivated autophagy in GBM.",2018 Sep 24,"['Zielke, Svenja', 'Meyer, Nina', 'Mari, Muriel', 'Abou-El-Ardat, Khalil', 'Reggiori, Fulvio', 'van Wijk, Sjoerd J. L.', 'Kögel, Donat', 'Fulda, Simone']",Cell Death Dis,,,False
e5d1fd5c8ca1cb299a376d2b3109b4088b0c9ae5,PMC,"Loperamide, pimozide, and STF-62247 trigger autophagy-dependent cell death in glioblastoma cells",http://dx.doi.org/10.1038/s41419-018-1003-1,PMC6155211,30250198,CC BY,"Autophagy is a well-described degradation mechanism that promotes cell survival upon nutrient starvation and other forms of cellular stresses. In addition, there is growing evidence showing that autophagy can exert a lethal function via autophagic cell death (ACD). As ACD has been implicated in apoptosis-resistant glioblastoma (GBM), there is a high medical need for identifying novel ACD-inducing drugs. Therefore, we screened a library containing 70 autophagy-inducing compounds to induce ATG5-dependent cell death in human MZ-54 GBM cells. Here, we identified three compounds, i.e. loperamide, pimozide, and STF-62247 that significantly induce cell death in several GBM cell lines compared to CRISPR/Cas9-generated ATG5- or ATG7-deficient cells, pointing to a death-promoting role of autophagy. Further cell death analyses conducted using pharmacological inhibitors revealed that apoptosis, ferroptosis, and necroptosis only play minor roles in loperamide-, pimozide- or STF-62247-induced cell death. Intriguingly, these three compounds induce massive lipidation of the autophagy marker protein LC3B as well as the formation of LC3B puncta, which are characteristic of autophagy. Furthermore, loperamide, pimozide, and STF-62247 enhance the autophagic flux in parental MZ-54 cells, but not in ATG5 or ATG7 knockout (KO) MZ-54 cells. In addition, loperamide- and pimozide-treated cells display a massive formation of autophagosomes and autolysosomes at the ultrastructural level. Finally, stimulation of autophagy by all three compounds is accompanied by dephosphorylation of mammalian target of rapamycin complex 1 (mTORC1), a well-known negative regulator of autophagy. In summary, our results indicate that loperamide, pimozide, and STF-62247 induce ATG5- and ATG7-dependent cell death in GBM cells, which is preceded by a massive induction of autophagy. These findings emphasize the lethal function and potential clinical relevance of hyperactivated autophagy in GBM.",2018 Sep 24,"['Zielke, Svenja', 'Meyer, Nina', 'Mari, Muriel', 'Abou-El-Ardat, Khalil', 'Reggiori, Fulvio', 'van Wijk, Sjoerd J. L.', 'Kögel, Donat', 'Fulda, Simone']",Cell Death Dis,,,True
6c7ee2062b49226bfee08114f12cb1cd07509d9d,PMC,The Formyl Peptide Receptors: Diversity of Ligands and Mechanism for Recognition,http://dx.doi.org/10.3390/molecules22030455,PMC6155412,28335409,CC BY,"The formyl peptide receptors (FPRs) are G protein-coupled receptors that transduce chemotactic signals in phagocytes and mediate host-defense as well as inflammatory responses including cell adhesion, directed migration, granule release and superoxide production. In recent years, the cellular distribution and biological functions of FPRs have expanded to include additional roles in homeostasis of organ functions and modulation of inflammation. In a prototype, FPRs recognize peptides containing N-formylated methionine such as those produced in bacteria and mitochondria, thereby serving as pattern recognition receptors. The repertoire of FPR ligands, however, has expanded rapidly to include not only N-formyl peptides from microbes but also non-formyl peptides of microbial and host origins, synthetic small molecules and an eicosanoid. How these chemically diverse ligands are recognized by the three human FPRs (FPR1, FPR2 and FPR3) and their murine equivalents is largely unclear. In the absence of crystal structures for the FPRs, site-directed mutagenesis, computer-aided ligand docking and structural simulation have led to the identification of amino acids within FPR1 and FPR2 that interact with several formyl peptides. This review article summarizes the progress made in the understanding of FPR ligand diversity as well as ligand recognition mechanisms used by these receptors.",2017 Mar 13,"['He, Hui-Qiong', 'Ye, Richard D.']",Molecules,,,True
6285a0930a05dfe14ae9f09101a789e070435b3f,PMC,"A Review on the Phytochemistry, Pharmacology, and Pharmacokinetics of Amentoflavone, a Naturally-Occurring Biflavonoid",http://dx.doi.org/10.3390/molecules22020299,PMC6155574,28212342,CC BY,"Amentoflavone (C(30)H(18)O(10)) is a well-known biflavonoid occurring in many natural plants. This polyphenolic compound has been discovered to have some important bioactivities, including anti-inflammation, anti-oxidation, anti-diabetes, and anti-senescence effects on many important reactions in the cardiovascular and central nervous system, etc. Over 120 plants have been found to contain this bioactive component, such as Selaginellaceae, Cupressaceae, Euphorbiaceae, Podocarpaceae, and Calophyllaceae plant families. This review paper aims to profile amentoflavone on its plant sources, natural derivatives, pharmacology, and pharmacokinetics, and to highlight some existing issues and perspectives in the future.",2017 Feb 16,"['Yu, Sheng', 'Yan, Hui', 'Zhang, Li', 'Shan, Mingqiu', 'Chen, Peidong', 'Ding, Anwei', 'Li, Sam Fong Yau']",Molecules,,,True
89ec194732e513702a5ec1539e1941140c476068,PMC,Purification of Houttuynia cordata Thunb. Essential Oil Using Macroporous Resin Followed by Microemulsion Encapsulation to Improve Its Safety and Antiviral Activity,http://dx.doi.org/10.3390/molecules22020293,PMC6155675,28212296,CC BY,"Essential oil extracted from Houttuynia cordata Thunb. (H. cordata) is widely used in traditional Chinese medicine due to its excellent biological activities. However, impurities and deficient preparations of the essential oil limit its safety and effectiveness. Herein, we proposed a strategy to prepare H. cordata essential oil (HEO) safely and effectively by combining the solvent extraction and the macroporous resin purification flexibly, and then encapsulating it using microemulsion. The extraction and purification process were optimized by orthogonal experimental design and adsorption-desorption tests, respectively. The average houttuynin content in pure HEO was then validated at 44.3% ± 2.01%, which presented a great potential for industrial application. Subsequently, pure HEO-loaded microemulsion was prepared by high-pressure homogenization and was then fully characterized. Results showed that the pure HEO-loaded microemulsion was successfully prepared with an average particle size of 179.1 nm and a high encapsulation rate of 94.7%. Furthermore, safety evaluation tests and in vitro antiviral testing indicated that the safety and activity of HEO were significantly improved after purification using D101 resin and were further improved by microemulsion encapsulation. These results demonstrated that the purification of HEO by macroporous resin followed by microemulsion encapsulation would be a promising approach for industrial application of HEO for the antiviral therapies.",2017 Feb 15,"['Pang, Jianmei', 'Dong, Wujun', 'Li, Yuhuan', 'Xia, Xuejun', 'Liu, Zhihua', 'Hao, Huazhen', 'Jiang, Lingmin', 'Liu, Yuling']",Molecules,,,True
25eca606303e4a141d7f3f4a1c2e4e8138e9667c,PMC,Isolation and Characterization of a Phaseolus vulgaris Trypsin Inhibitor with Antiproliferative Activity on Leukemia and Lymphoma Cells,http://dx.doi.org/10.3390/molecules22010187,PMC6155916,28125005,CC BY,"A 17.5-kDa trypsin inhibitor was purified from Phaseolus vulgaris cv. “gold bean” with an isolation protocol including ion exchange chromatography on DEAE-cellulose (Diethylaminoethyl-cellulose), affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-sepharose (Sulfopropyl-sepharose), and gel filtration by FPLC (Fast protein liquid chromatography) on Superdex 75. It dose-dependently inhibited trypsin with an IC(50) value of 0.4 μM, and this activity was reduced in the presence of dithiothreitol in a dose- and time-dependent manner, signifying the importance of the disulfide linkage to the activity. It inhibited [methyl-(3)H] thymidine incorporation by leukemia L1210 cells and lymphoma MBL2 cells with an IC(50) value of 2.3 μM and 2.5 μM, respectively. The inhibitor had no effect on fungal growth and the activities of various viral enzymes when tested up to 100 μM.",2017 Jan 23,"['Li, Miao', 'Liu, Qin', 'Cui, Yajuan', 'Li, Dong', 'Wang, Hexiang', 'Ng, Tzi Bun']",Molecules,,,True
5e93750f999d2d9a74e43f51d61de527957e8502,PMC,The association between transforming growth factor beta1 polymorphism and susceptibility to pulmonary fibrosis: A meta-analysis (MOOSE compliant),http://dx.doi.org/10.1097/MD.0000000000011876,PMC6155963,30212926,CC BY,"Although many studies have investigated the association of single nucleotide polymorphisms (SNPs) in transforming growth factor beta1 (TGF-β1) gene with pulmonary fibrosis (PF), but their association is still controversial. To clarify this, we performed a meta-analysis. Studies related to TGF-β1 and PF were retrieved from PubMed, Medline, Embase, Scopus, and Wanfang (up to November 30, 2017). We targeted TGF-β1 SNPs that have been reported by ≥3 studies to be included in the current meta-analysis, resulting in only 1 final SNP (rs1800470). The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in the models of allele comparison (T vs C), homozygote comparison (TT vs CC), dominant (TT vs TC + CC), recessive (TT + TC vs CC) to evaluate the strength of the associations. A total of 7 case-control studies were included in this meta-analysis. Overall, no significant association between TGF-β1 rs1800470 and PF was found (T vs C: OR [95% CI] = 0.96 [0.80, 1.15]; TT vs CC: 0.87 [0.61, 1.22]; TT vs TC + CC: 0.80 [0.62, 1.04]; TT + TC vs CC: 1.13 [0.83, 1.54]). In subgroup analyses by ethnicity or original disease, no statistically significant association between TGF-β1 rs1800470 polymorphisms and PF was demonstrated. This meta-analysis revealed that TGF-β1 rs1800470 polymorphism was not associated with susceptibility to PF development.",2018 Sep 14,"['Xin, Lili', 'Jiang, Miao', 'Su, Guangbao', 'Xie, Miao', 'Chen, Hui', 'Liu, Xiao', 'Xu, Muge', 'Zhang, Geng', 'Gong, Jiening']",Medicine (Baltimore),,,True
61143198570c983e9975d2c20a361749d92396df,PMC,Testing the neutral theory of biodiversity with the microbiome dataset from cystic fibrosis patients,http://dx.doi.org/10.1097/MD.0000000000012248,PMC6156045,30212959,CC BY,"Cystic fibrosis (CF) is a hereditary disease that is characterized by defective mucociliary clearance, airway obstruction, chronic infection, and persistent inflammation. Cystic fibrosis pulmonary exacerbation (CFPE) majorly causes the morbidity of CF patients. Although CF has been demonstrated to change the composition of lung microbial community, previous studies have not made efforts to study the differences in the mechanism of assembly and diversity maintenance of lung microbial community in CF patients. In this study, we applied the neutral theory of biodiversity to comparatively investigate the assembly and diversity maintenance of the lung microbial community before and after the antibiotic treatment by reanalyzing the dataset from Fodor et al's study. We found that no one sample in the lung microbial communities of the sputum samples of Exacerbation group, nor those of End-of-treatment group satisfied the predictions of neutral model, suggesting that the neutral-process does not dominate in CF patients before and after antibiotic treatments. By comparing the biodiversity parameter between Exacerbation and End-of-treatment group, we found that the former had the significantly higher biodiversity, but the change in diversity parameter is slight and the P value is close to.05 (P value = .41). Therefore, our second finding is that although CFPE may increase the biodiversity of lung microbial community, the change is not essential.",2018 Sep 14,"['Huang, Qi', 'Wang, Yaqiang', 'Xia, Yao', 'Li, Lianwei', 'Luo, Juan', 'Xia, Shuxian', 'Sun, Yang', 'Miao, Yinglei', 'Wang, Kunhua', 'Chen, Ye']",Medicine (Baltimore),,,True
feeef400771697981198a218da58c34ebb7963a0,PMC,Genome Sequence of Peacock Reveals the Peculiar Case of a Glittering Bird,http://dx.doi.org/10.3389/fgene.2018.00392,PMC6156156,30283495,CC BY,"The unique ornamental features and extreme sexual traits of Peacock have always intrigued scientists and naturalists for centuries. However, the genomic basis of these phenotypes are yet unknown. Here, we report the first genome sequence and comparative analysis of peacock with the high quality genomes of chicken, turkey, duck, flycatcher and zebra finch. Genes involved in early developmental pathways including TGF-β, BMP, and Wnt signaling, which have been shown to be involved in feather patterning, bone morphogenesis, and skeletal muscle development, revealed signs of adaptive evolution and provided useful clues on the phenotypes of peacock. Innate and adaptive immune genes involved in complement system and T-cell response also showed signs of adaptive evolution in peacock suggesting their possible role in building a robust immune system which is consistent with the predictions of the Hamilton–Zuk hypothesis. This study provides novel genomic and evolutionary insights into the molecular understanding toward the phenotypic evolution of Indian peacock.",2018 Sep 19,"['Jaiswal, Shubham K.', 'Gupta, Ankit', 'Saxena, Rituja', 'Prasoodanan, Vishnu P. K.', 'Sharma, Ashok K.', 'Mittal, Parul', 'Roy, Ankita', 'Shafer, Aaron B. A.', 'Vijay, Nagarjun', 'Sharma, Vineet K.']",Front Genet,,,True
377c6ff0f04a67152f6029e2836500abddac3d57,PMC,Comparative Viral Sampling in the Sinonasal Passages; Different Viruses at Different Sites,http://dx.doi.org/10.3389/fcimb.2018.00334,PMC6156342,30283747,CC BY,"Background: With the emergence of the microbiome as an important factor in health and disease in the respiratory tract standardised, validated techniques are required for its accurate characterisation. No standardised technique has been reported specifically for viral sampling in the sinonasal passages. Aim: To optimise viral sampling techniques from the sinonasal cavity. Methods: Sterile cytology brushes were used under endoscopic guidance to sample the sinonasal mucosa at time of endoscopic sinus surgery at both the middle and inferior meatuses (MM and IM). DNA and RNA were extracted from the samples and underwent PCR or RT-PCR testing, respectively, for a panel of 15 common upper respiratory tract viruses. Results: Twenty-four adult patients were recruited for this study. 18/24 (75%) patients were positive for virus in at least one site, while 8/24 (33%) were positive for virus at both sites. The mean number of viruses identified at the two sites were similar (0.875 ± 0.899 at the MM vs. 0.750 ± 1.032 at the IM). 6/24 (25%) of patients showed no virus at either site, while 3/24 (12.5%) demonstrated the same viral species at both sites. Conclusion: Although the number of viruses present at different sites with the nasal cavity are similar, discord exists in the viral species between sites. It is therefore recommended that both sites are sampled in the clinical and research setting better to characterise the viral species within the nasal cavity.",2018 Sep 19,"['Goggin, Rachel K.', 'Bennett, Catherine A.', 'Bassiouni, Ahmed', 'Bialasiewicz, Seweryn', 'Vreugde, Sarah', 'Wormald, Peter-John', 'Psaltis, Alkis J.']",Front Cell Infect Microbiol,,,True
2ad6ccc77d12ec8c8f91076fd337a01d734e578e,PMC,New Vaccine Technologies to Combat Outbreak Situations,http://dx.doi.org/10.3389/fimmu.2018.01963,PMC6156540,30283434,CC BY,"Ever since the development of the first vaccine more than 200 years ago, vaccinations have greatly decreased the burden of infectious diseases worldwide, famously leading to the eradication of small pox and allowing the restriction of diseases such as polio, tetanus, diphtheria, and measles. A multitude of research efforts focuses on the improvement of established and the discovery of new vaccines such as the HPV (human papilloma virus) vaccine in 2006. However, radical changes in the density, age distribution and traveling habits of the population worldwide as well as the changing climate favor the emergence of old and new pathogens that bear the risk of becoming pandemic threats. In recent years, the rapid spread of severe infections such as HIV, SARS, Ebola, and Zika have highlighted the dire need for global preparedness for pandemics, which necessitates the extremely rapid development and comprehensive distribution of vaccines against potentially previously unknown pathogens. What is more, the emergence of antibiotic resistant bacteria calls for new approaches to prevent infections. Given these changes, established methods for the identification of new vaccine candidates are no longer sufficient to ensure global protection. Hence, new vaccine technologies able to achieve rapid development as well as large scale production are of pivotal importance. This review will discuss viral vector and nucleic acid-based vaccines (DNA and mRNA vaccines) as new approaches that might be able to tackle these challenges to global health.",2018 Sep 19,"['Rauch, Susanne', 'Jasny, Edith', 'Schmidt, Kim E.', 'Petsch, Benjamin']",Front Immunol,,,True
70adc25ffcec7b3d1871ea866658c3cd01080f49,PMC,Transcriptional profiles of PBMCs from pigs infected with three genetically diverse porcine reproductive and respiratory syndrome virus strains,http://dx.doi.org/10.1007/s11033-018-4204-x,PMC6156768,29882085,CC BY,"Porcine reproductive and respiratory syndrome virus is the cause of reproductive failure in sows and respiratory disease in young pigs, which has been considered as one of the most costly diseases to the worldwide pig industry for almost 30 years. This study used microarray-based transcriptomic analysis of PBMCs from experimentally infected pigs to explore the patterns of immune dysregulation after infection with two East European PRRSV strains from subtype 2 (BOR and ILI) in comparison to a Danish subtype 1 strain (DAN). Transcriptional profiles were determined at day 7 post infection in three tested groups of pigs and analysed in comparison with the expression profile of control group. Microarray analysis revealed differential regulation (> 1.5-fold change) of 4253 and 7335 genes in groups infected with BOR and ILI strains, respectively, and of 12518 genes in pigs infected with Danish strain. Subtype 2 PRRSV strains showed greater induction of many genes, especially those involved in innate immunity, such as interferon stimulated antiviral genes and inflammatory markers. Functional analysis of the microarray data revealed a significant up-regulation of genes involved in processes such as acute phase response, granulocyte and agranulocyte adhesion and diapedesis, as well as down-regulation of genes enrolled in pathways engaged in protein synthesis, cell division, as well as B and T cell signaling. This study provided an insight into the host response to three different PRRSV strains at a molecular level and demonstrated variability between strains of different pathogenicity level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11033-018-4204-x) contains supplementary material, which is available to authorized users.",2018 Jun 7,"['Rola-Łuszczak, Marzena', 'Materniak-Kornas, Magdalena', 'Pluta, Aneta', 'Podgórska, Katarzyna', 'Nielsen, Jens', 'Stadejek, Tomasz', 'Kuźmak, Jacek']",Mol Biol Rep,,,True
85bc7c0784157ee7c3d3091e40aa1e45b560d26b,PMC,Applying graph theory to protein structures: an Atlas of coiled coils,http://dx.doi.org/10.1093/bioinformatics/bty347,PMC6157074,29722888,CC BY,"MOTIVATION: To understand protein structure, folding and function fully and to design proteins de novo reliably, we must learn from natural protein structures that have been characterized experimentally. The number of protein structures available is large and growing exponentially, which makes this task challenging. Indeed, computational resources are becoming increasingly important for classifying and analyzing this resource. Here, we use tools from graph theory to define an Atlas classification scheme for automatically categorizing certain protein substructures. RESULTS: Focusing on the α-helical coiled coils, which are ubiquitous protein-structure and protein–protein interaction motifs, we present a suite of computational resources designed for analyzing these assemblies. iSOCKET enables interactive analysis of side-chain packing within proteins to identify coiled coils automatically and with considerable user control. Applying a graph theory-based Atlas classification scheme to structures identified by iSOCKET gives the Atlas of Coiled Coils, a fully automated, updated overview of extant coiled coils. The utility of this approach is illustrated with the first formal classification of an emerging subclass of coiled coils called α-helical barrels. Furthermore, in the Atlas, the known coiled-coil universe is presented alongside a partial enumeration of the ‘dark matter’ of coiled-coil structures; i.e. those coiled-coil architectures that are theoretically possible but have not been observed to date, and thus present defined targets for protein design. AVAILABILITY AND IMPLEMENTATION: iSOCKET is available as part of the open-source GitHub repository associated with this work (https://github.com/woolfson-group/isocket). This repository also contains all the data generated when classifying the protein graphs. The Atlas of Coiled Coils is available at: http://coiledcoils.chm.bris.ac.uk/atlas/app.",2018 Oct 1,"['Heal, Jack W', 'Bartlett, Gail J', 'Wood, Christopher W', 'Thomson, Andrew R', 'Woolfson, Derek N']",Bioinformatics,,,True
6ed9a8fa706f8553d2111e38145c95990b26ba9b,PMC,Prevalence of Human Bocavirus in Africa and Other Developing Countries between 2005 and 2016: A Potential Emerging Viral Pathogen for Diarrhea,http://dx.doi.org/10.1155/2018/7875482,PMC6157109,30275840,CC BY,"BACKGROUND: Human Bocavirus (HBoV) is an emerging virus discovered in 2005 from individuals suffering gastroenteritis and respiratory tract infections. Numerous studies related to the epidemiology and pathogenesis of HBoV have been conducted worldwide. This review reports on HBoV studies in individuals with acute gastroenteritis, with and without respiratory tract infections in Africa between 2005 and 2016. MATERIAL AND METHOD: The search engines of PubMed, Google Scholar, and Embase database for published articles of HBoV were used to obtain data between 2005 and 2016. The search words included were as follows: studies performed in Africa or/other developing countries or/worldwide; studies for the detection of HBoV in patients with/without diarrhea and respiratory tract infection; studies using standardized laboratory techniques for detection. RESULTS: The search yielded a total of 756 publications with 70 studies meeting the inclusion criteria. Studies included children and individuals of all age groups. HBoV prevalence in Africa was 13% in individuals suffering gastroenteritis with/without respiratory tract infection. CONCLUSION: Reports suggest that HBoV infections are increasingly being recognized worldwide. Therefore, surveillance of individuals suffering from infections in Africa is required to monitor the prevalence of HBoV and help understand the role of HBoV in individuals suffering from gastroenteritis with/without respiratory tract infection.",2018 Sep 12,"['Rikhotso, Mpumelelo Casper', 'Kabue, Jean Pierre', 'Ledwaba, Solanka Ellen', 'Traoré, Afsatou Ndama', 'Potgieter, Natasha']",J Trop Med,,,True
5af166022c0575cefcd0f2107b4fd1a657b6391b,PMC,Going to Bat(s) for Studies of Disease Tolerance,http://dx.doi.org/10.3389/fimmu.2018.02112,PMC6158362,30294323,CC BY,"A majority of viruses that have caused recent epidemics with high lethality rates in people, are zoonoses originating from wildlife. Among them are filoviruses (e.g., Marburg, Ebola), coronaviruses (e.g., SARS, MERS), henipaviruses (e.g., Hendra, Nipah) which share the common features that they are all RNA viruses, and that a dysregulated immune response is an important contributor to the tissue damage and hence pathogenicity that results from infection in humans. Intriguingly, these viruses also all originate from bat reservoirs. Bats have been shown to have a greater mean viral richness than predicted by their phylogenetic distance from humans, their geographic range, or their presence in urban areas, suggesting other traits must explain why bats harbor a greater number of zoonotic viruses than other mammals. Bats are highly unusual among mammals in other ways as well. Not only are they the only mammals capable of powered flight, they have extraordinarily long life spans, with little detectable increases in mortality or senescence until high ages. Their physiology likely impacted their history of pathogen exposure and necessitated adaptations that may have also affected immune signaling pathways. Do our life history traits make us susceptible to generating damaging immune responses to RNA viruses or does the physiology of bats make them particularly tolerant or resistant? Understanding what immune mechanisms enable bats to coexist with RNA viruses may provide critical fundamental insights into how to achieve greater resilience in humans.",2018 Sep 20,"['Mandl, Judith N.', 'Schneider, Caitlin', 'Schneider, David S.', 'Baker, Michelle L.']",Front Immunol,,,True
fcce653525bba82ca40e8934a2e37ee4de6e2c23,PMC,Epidemiology and Transmission of Respiratory Infections in Thai Army Recruits: A Prospective Cohort Study,http://dx.doi.org/10.4269/ajtmh.18-0219,PMC6159564,30182916,CC BY,"Military recruits are at high risk of respiratory infections. However, limited data exist on military populations in tropical settings, where the epidemiology of respiratory infections differs substantially from temperate settings. We enrolled recruits undertaking a 10-week military training at two Royal Thai Army barracks between May 2014 and July 2015. We used a multiplex respiratory panel to analyze nose and throat swabs collected at the start and end of the training period, and from participants experiencing respiratory symptoms during follow-up. Paired sera were tested for influenza seroconversion using a hemagglutinin inhibition assay. Overall rates of upper respiratory illness and influenza-like illness were 3.1 and 2.0 episodes per 100 person-weeks, respectively. A pathogen was detected in 96% of samples. The most commonly detected microbes were Haemophilus influenzae type B (62.7%) or non–type B (58.2%) and rhinovirus (22.4%). At baseline, bacterial colonization was high and included H. influenzae type B (82.3%), H. influenzae non–type B (31.5%), Klebsiella pneumoniae (14.6%), Staphylococcus aureus (8.5%), and Streptococcus pneumoniae (8.5%). At the end of follow-up, colonization with H. influenzae non–type B had increased to 74.1%, and S. pneumoniae to 33.6%. In the serology subset, the rate of influenza infection was 3.4 per 100 person-months; 58% of influenza infections resulted in clinical disease. Our study provides key data on the epidemiology and transmission of respiratory pathogens in tropical settings. Our results emphasize the need for improved infection prevention and control in military environments, given the high burden of illness and potential for intense transmission of respiratory pathogens.",2018 Oct 4,"['Tam, Clarence C.', 'Anderson, Kathryn B.', 'Offeddu, Vittoria', 'Weg, Alden', 'Macareo, Louis R.', 'Ellison, Damon W.', 'Rangsin, Ram', 'Fernandez, Stefan', 'Gibbons, Robert V.', 'Yoon, In-Kyu', 'Simasathien, Sriluck']",Am J Trop Med Hyg,,,True
d664db83c3b42b97a63c0172ab70c96f834181e0,PMC,Epidemiology and Transmission of Respiratory Infections in Thai Army Recruits: A Prospective Cohort Study,http://dx.doi.org/10.4269/ajtmh.18-0219,PMC6159564,30182916,CC BY,"Military recruits are at high risk of respiratory infections. However, limited data exist on military populations in tropical settings, where the epidemiology of respiratory infections differs substantially from temperate settings. We enrolled recruits undertaking a 10-week military training at two Royal Thai Army barracks between May 2014 and July 2015. We used a multiplex respiratory panel to analyze nose and throat swabs collected at the start and end of the training period, and from participants experiencing respiratory symptoms during follow-up. Paired sera were tested for influenza seroconversion using a hemagglutinin inhibition assay. Overall rates of upper respiratory illness and influenza-like illness were 3.1 and 2.0 episodes per 100 person-weeks, respectively. A pathogen was detected in 96% of samples. The most commonly detected microbes were Haemophilus influenzae type B (62.7%) or non–type B (58.2%) and rhinovirus (22.4%). At baseline, bacterial colonization was high and included H. influenzae type B (82.3%), H. influenzae non–type B (31.5%), Klebsiella pneumoniae (14.6%), Staphylococcus aureus (8.5%), and Streptococcus pneumoniae (8.5%). At the end of follow-up, colonization with H. influenzae non–type B had increased to 74.1%, and S. pneumoniae to 33.6%. In the serology subset, the rate of influenza infection was 3.4 per 100 person-months; 58% of influenza infections resulted in clinical disease. Our study provides key data on the epidemiology and transmission of respiratory pathogens in tropical settings. Our results emphasize the need for improved infection prevention and control in military environments, given the high burden of illness and potential for intense transmission of respiratory pathogens.",2018 Oct 4,"['Tam, Clarence C.', 'Anderson, Kathryn B.', 'Offeddu, Vittoria', 'Weg, Alden', 'Macareo, Louis R.', 'Ellison, Damon W.', 'Rangsin, Ram', 'Fernandez, Stefan', 'Gibbons, Robert V.', 'Yoon, In-Kyu', 'Simasathien, Sriluck']",Am J Trop Med Hyg,,,False
c4243eccc82c5b1f6a7cfe910e2167556feab414,PMC,Defeating re-emerging Alkhurma hemorrhagic fever virus outbreak in Saudi Arabia and worldwide,http://dx.doi.org/10.1371/journal.pntd.0006707,PMC6159858,30260960,CC BY,,2018 Sep 27,"['Tambo, Ernest', 'El-Dessouky, Ashraf G.']",PLoS Negl Trop Dis,,,True
6b83ccbaff4b9d9f4ac38fcfbbb2bdde5b3c53aa,PMC,"Genetic diversity, infection prevalence, and possible transmission routes of Bartonella spp. in vampire bats",http://dx.doi.org/10.1371/journal.pntd.0006786,PMC6159870,30260954,CC BY,"Bartonella spp. are globally distributed bacteria that cause endocarditis in humans and domestic animals. Recent work has suggested bats as zoonotic reservoirs of some human Bartonella infections; however, the ecological and spatiotemporal patterns of infection in bats remain largely unknown. Here we studied the genetic diversity, prevalence of infection across seasons and years, individual risk factors, and possible transmission routes of Bartonella in populations of common vampire bats (Desmodus rotundus) in Peru and Belize, for which high infection prevalence has previously been reported. Phylogenetic analysis of the gltA gene for a subset of PCR-positive blood samples revealed sequences that were related to Bartonella described from vampire bats from Mexico, other Neotropical bat species, and streblid bat flies. Sequences associated with vampire bats clustered significantly by country but commonly spanned Central and South America, implying limited spatial structure. Stable and nonzero Bartonella prevalence between years supported endemic transmission in all sites. The odds of Bartonella infection for individual bats was unrelated to the intensity of bat flies ectoparasitism, but nearly all infected bats were infested, which precluded conclusive assessment of support for vector-borne transmission. While metagenomic sequencing found no strong evidence of Bartonella DNA in pooled bat saliva and fecal samples, we detected PCR positivity in individual saliva and feces, suggesting the potential for bacterial transmission through both direct contact (i.e., biting) and environmental (i.e., fecal) exposures. Further investigating the relative contributions of direct contact, environmental, and vector-borne transmission for bat Bartonella is an important next step to predict infection dynamics within bats and the risks of human and livestock exposures.",2018 Sep 27,"['Becker, Daniel J.', 'Bergner, Laura M.', 'Bentz, Alexandra B.', 'Orton, Richard J.', 'Altizer, Sonia', 'Streicker, Daniel G.']",PLoS Negl Trop Dis,,,True
724ad7162949626684d0b7627a7a4ef477259f8a,PMC,Comparative evaluation of a laboratory-developed real-time PCR assay and RealStar® Adenovirus PCR Kit for quantitative detection of human adenovirus,http://dx.doi.org/10.1186/s12985-018-1059-7,PMC6161464,30261891,CC BY,"BACKGROUND: Human adenoviruses are common causes of community-acquired respiratory tract and enteric infections. Severe disseminated infections with high mortality rates may be seen in immunocompromised individuals. An accurate and cost-effective quantitative assay is essential not only for laboratory diagnosis of adenoviral infections, but also for monitoring of response to antiviral treatment. The diagnostic performance of an in-house quantitative polymerase chain reaction assay was compared to a commercial system. METHODS: The analytical sensitivity, specificity, linearity, precision and accuracy of an in-house adenovirus quantitative polymerase chain reaction assay were evaluated against the RealStar® Adenovirus PCR Kit (Altona Diagnostics GmbH, Hamburg, Germany), using 122 clinical specimens and 18 proficiency testing samples. RESULTS: Linear regression analysis of the quantitative results by the in-house assay showed the dynamic range from 2.60 to 9 log(10) (plasma) and 2.94 to 9 log(10) (viral transport medium) copies/mL, with the coefficient of determination (R(2)) of 0.996 and 0.998, respectively. A dilution series demonstrated the limits of detection and lower limits of quantification for plasma were 2.06 log(10) and 2.60 log(10) copies/mL and those for viral transport medium were 2.31 log(10) and 2.94 log(10) copies/mL respectively. The precision of the in-house assay was highly reproducible among runs with coefficients of variance ranging from 0.07 to 3.21% for plasma and 0.17% to 2.11% for viral transport medium. A comparison of 52 matched samples showed an excellent correlation between the quantitative viral loads measured by the in-house assay and the RealStar® Adenovirus PCR Kit (R(2) = 0.984), with an average bias of − 0.16 log(10) copies/mL. CONCLUSIONS: The in-house adenovirus assay is a sensitive and reliable assay with lower cost for the detection and quantification of adenoviral DNA when compared to the RealStar® Adenovirus PCR Kit. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1059-7) contains supplementary material, which is available to authorized users.",2018 Sep 27,"['Wong, Samson S. Y.', 'Yip, Cyril C. Y.', 'Sridhar, Siddharth', 'Leung, Kit-Hang', 'Cheng, Andrew K. W.', 'Fung, Ami M. Y.', 'Lam, Ho-Yin', 'Chan, Kwok-Hung', 'Chan, Jasper F. W.', 'Cheng, Vincent C. C.', 'Tang, Bone S. F.', 'Yuen, Kwok-Yung']",Virol J,,,False
bb6d4ff2bd0aa48e1d8b2b18f937a244cd806212,PMC,Comparative evaluation of a laboratory-developed real-time PCR assay and RealStar® Adenovirus PCR Kit for quantitative detection of human adenovirus,http://dx.doi.org/10.1186/s12985-018-1059-7,PMC6161464,30261891,CC BY,"BACKGROUND: Human adenoviruses are common causes of community-acquired respiratory tract and enteric infections. Severe disseminated infections with high mortality rates may be seen in immunocompromised individuals. An accurate and cost-effective quantitative assay is essential not only for laboratory diagnosis of adenoviral infections, but also for monitoring of response to antiviral treatment. The diagnostic performance of an in-house quantitative polymerase chain reaction assay was compared to a commercial system. METHODS: The analytical sensitivity, specificity, linearity, precision and accuracy of an in-house adenovirus quantitative polymerase chain reaction assay were evaluated against the RealStar® Adenovirus PCR Kit (Altona Diagnostics GmbH, Hamburg, Germany), using 122 clinical specimens and 18 proficiency testing samples. RESULTS: Linear regression analysis of the quantitative results by the in-house assay showed the dynamic range from 2.60 to 9 log(10) (plasma) and 2.94 to 9 log(10) (viral transport medium) copies/mL, with the coefficient of determination (R(2)) of 0.996 and 0.998, respectively. A dilution series demonstrated the limits of detection and lower limits of quantification for plasma were 2.06 log(10) and 2.60 log(10) copies/mL and those for viral transport medium were 2.31 log(10) and 2.94 log(10) copies/mL respectively. The precision of the in-house assay was highly reproducible among runs with coefficients of variance ranging from 0.07 to 3.21% for plasma and 0.17% to 2.11% for viral transport medium. A comparison of 52 matched samples showed an excellent correlation between the quantitative viral loads measured by the in-house assay and the RealStar® Adenovirus PCR Kit (R(2) = 0.984), with an average bias of − 0.16 log(10) copies/mL. CONCLUSIONS: The in-house adenovirus assay is a sensitive and reliable assay with lower cost for the detection and quantification of adenoviral DNA when compared to the RealStar® Adenovirus PCR Kit. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1059-7) contains supplementary material, which is available to authorized users.",2018 Sep 27,"['Wong, Samson S. Y.', 'Yip, Cyril C. Y.', 'Sridhar, Siddharth', 'Leung, Kit-Hang', 'Cheng, Andrew K. W.', 'Fung, Ami M. Y.', 'Lam, Ho-Yin', 'Chan, Kwok-Hung', 'Chan, Jasper F. W.', 'Cheng, Vincent C. C.', 'Tang, Bone S. F.', 'Yuen, Kwok-Yung']",Virol J,,,True
a62150169f3f45fa30e13124ba0ff6c1945f5c0e,PMC,Host phosphatidic acid phosphatase lipin1 is rate limiting for functional hepatitis C virus replicase complex formation,http://dx.doi.org/10.1371/journal.ppat.1007284,PMC6161900,30226904,CC BY,"Hepatitis C virus (HCV) infection constitutes a significant health burden worldwide, because it is a major etiologic agent of chronic liver disease, cirrhosis and hepatocellular carcinoma. HCV replication cycle is closely tied to lipid metabolism and infection by this virus causes profound changes in host lipid homeostasis. We focused our attention on a phosphatidate phosphate (PAP) enzyme family (the lipin family), which mediate the conversion of phosphatidate to diacylglycerol in the cytoplasm, playing a key role in triglyceride biosynthesis and in phospholipid homeostasis. Lipins may also translocate to the nucleus to act as transcriptional regulators of genes involved in lipid metabolism. The best-characterized member of this family is lipin1, which cooperates with lipin2 to maintain glycerophospholipid homeostasis in the liver. Lipin1-deficient cell lines were generated by RNAi to study the role of this protein in different steps of HCV replication cycle. Using surrogate models that recapitulate different aspects of HCV infection, we concluded that lipin1 is rate limiting for the generation of functional replicase complexes, in a step downstream primary translation that leads to early HCV RNA replication. Infection studies in lipin1-deficient cells overexpressing wild type or phosphatase-defective lipin1 proteins suggest that lipin1 phosphatase activity is required to support HCV infection. Finally, ultrastructural and biochemical analyses in replication-independent models suggest that lipin1 may facilitate the generation of the membranous compartment that contains functional HCV replicase complexes.",2018 Sep 18,"['Mingorance, Lidia', 'Castro, Victoria', 'Ávila-Pérez, Ginés', 'Calvo, Gema', 'Rodriguez, María Josefa', 'Carrascosa, José L.', 'Pérez-del-Pulgar, Sofía', 'Forns, Xavier', 'Gastaminza, Pablo']",PLoS Pathog,,,True
4859cb514e6cc4c0c1e9490205484a1511b17baa,PMC,IFITM proteins inhibit HIV-1 protein synthesis,http://dx.doi.org/10.1038/s41598-018-32785-5,PMC6162285,30266929,CC BY,"Interferon induced transmembrane proteins (IFITMs) inhibit the cellular entry of a broad range of viruses, but it has been suspected that for HIV-1 IFITMs may also inhibit a post-integration replicative step. We show that IFITM expression reduces HIV-1 viral protein synthesis by preferentially excluding viral mRNA transcripts from translation and thereby restricts viral production. Codon-optimization of proviral DNA rescues viral translation, implying that IFITM-mediated restriction requires recognition of viral RNA elements. In addition, we find that expression of the viral accessory protein Nef can help overcome the IFITM-mediated inhibition of virus production. Our studies identify a novel role for IFITMs in inhibiting HIV replication at the level of translation, but show that the effects can be overcome by the lentiviral protein Nef.",2018 Sep 28,"['Lee, Wing-Yiu Jason', 'Fu, Rebecca Menhua', 'Liang, Chen', 'Sloan, Richard D.']",Sci Rep,,,False
a2cf9e5c6c99b221516c4ce927b3c389d78c7620,PMC,IFITM proteins inhibit HIV-1 protein synthesis,http://dx.doi.org/10.1038/s41598-018-32785-5,PMC6162285,30266929,CC BY,"Interferon induced transmembrane proteins (IFITMs) inhibit the cellular entry of a broad range of viruses, but it has been suspected that for HIV-1 IFITMs may also inhibit a post-integration replicative step. We show that IFITM expression reduces HIV-1 viral protein synthesis by preferentially excluding viral mRNA transcripts from translation and thereby restricts viral production. Codon-optimization of proviral DNA rescues viral translation, implying that IFITM-mediated restriction requires recognition of viral RNA elements. In addition, we find that expression of the viral accessory protein Nef can help overcome the IFITM-mediated inhibition of virus production. Our studies identify a novel role for IFITMs in inhibiting HIV replication at the level of translation, but show that the effects can be overcome by the lentiviral protein Nef.",2018 Sep 28,"['Lee, Wing-Yiu Jason', 'Fu, Rebecca Menhua', 'Liang, Chen', 'Sloan, Richard D.']",Sci Rep,,,True
f9426bdcd204747d493857d5a88efaf70c2cbee5,PMC,Complemented Palindromic Small RNAs First Discovered from SARS Coronavirus,http://dx.doi.org/10.3390/genes9090442,PMC6162610,30189613,CC BY,"In this study, we report for the first time the existence of complemented palindromic small RNAs (cpsRNAs) and propose that cpsRNAs and palindromic small RNAs (psRNAs) constitute a novel class of small RNAs. The first discovered 19-nt cpsRNA UUAACAAGCUUGUUAAAGA, named SARS-CoV-cpsR-19, was detected from a 22-bp DNA complemented palindrome TCTTTAACAAGCTTGTTAAAGA in the severe acute respiratory syndrome coronavirus (SARS-CoV) genome. The phylogenetic analysis supported that this DNA complemented palindrome originated from bat betacoronavirus. The results of RNA interference (RNAi) experiments showed that one 19-nt segment corresponding to SARS-CoV-cpsR-19 significantly induced cell apoptosis. Using this joint analysis of the molecular function and phylogeny, our results suggested that SARS-CoV-cpsR-19 could play a role in SARS-CoV infection or pathogenesis. The discovery of cpsRNAs has paved a way to find novel markers for pathogen detection and to reveal the mechanisms underlying infection or pathogenesis from a different point of view. Researchers can use cpsRNAs to study the infection or pathogenesis of pathogenic viruses when these viruses are not available. The discovery of psRNAs and cpsRNAs, as a novel class of small RNAs, also inspire researchers to investigate DNA palindromes and DNA complemented palindromes with lengths of psRNAs and cpsRNAs in viral genomes.",2018 Sep 5,"['Liu, Chang', 'Chen, Ze', 'Hu, Yue', 'Ji, Haishuo', 'Yu, Deshui', 'Shen, Wenyuan', 'Li, Siyu', 'Ruan, Jishou', 'Bu, Wenjun', 'Gao, Shan']",Genes (Basel),,,True
ecdc5c17ed143ffed9542802ce029dd323bb6a28,PMC,Proteases and Their Inhibitors in Chronic Obstructive Pulmonary Disease,http://dx.doi.org/10.3390/jcm7090244,PMC6162857,30154365,CC BY,"In the context of respiratory disease, chronic obstructive pulmonary disease (COPD) is the leading cause of mortality worldwide. Despite much development in the area of drug development, currently there are no effective medicines available for the treatment of this disease. An imbalance in the protease: Antiprotease ratio in the COPD lung remains an important aspect of COPD pathophysiology and several studies have shown the efficacy of antiprotease therapy in both in vitro and in vivo COPD models. However more in-depth studies will be required to validate the efficacy of lead drug molecules targeting these proteases. This review discusses the current status of protease-directed drugs used for treating COPD and explores the future prospects of utilizing the potential of antiprotease-based therapeutics as a treatment for this disease.",2018 Aug 28,"['Dey, Tapan', 'Kalita, Jatin', 'Weldon, Sinéad', 'Taggart, Clifford C.']",J Clin Med,,,True
513f57a7efa430c143b840c17beb62c010429aac,PMC,Sharing public health data and information across borders: lessons from Southeast Asia,http://dx.doi.org/10.1186/s12992-018-0415-0,PMC6162912,30268139,CC BY,"BACKGROUND: The importance of data and information sharing for the prevention and control of infectious diseases has long been recognised. In recent years, public health emergencies such as avian influenza, drug-resistant malaria, and Ebola have brought renewed attention to the need for effective communication channels between health authorities, particularly in regional contexts where neighbouring countries share common health threats. However, little empirical research has been conducted to date to explore the range of factors that may affect the transfer, exchange, and use of public health data and expertise across borders, especially in developing contexts. METHODS: To explore these issues, 60 interviews were conducted with domestic and international stakeholders in Cambodia and Vietnam, selected amongst those who were involved in regional public health programmes and networks. Data analysis was structured around three categories mapped across the dataset: (1) the nature of shared data and information; (2) the nature of communication channels; and (3) how information flow may be affected by the local, regional, and global system of rules and arrangements. RESULTS: There has been a great intensification in the circulation of data, information, and expertise across borders in Southeast Asia. However, findings from this study document ways in which the movement of data and information from production sites to other places can be challenging due to different standards and practices, language barriers, different national structures and rules that govern the circulation of health information inside and outside countries, imbalances in capacities and power, and sustainability of financing arrangements. CONCLUSIONS: Our study highlights the complex socio-technical nature of data and information sharing, suggesting that best practices require significant involvement of an independent third-party brokering organisation or office, which can redress imbalances between country partners at different levels in the data sharing process, create meaningful communication channels and make the most of shared information and data sets.",2018 Sep 29,"['Liverani, Marco', 'Teng, Srey', 'Le, Minh Sat', 'Coker, Richard']",Global Health,,,True
5e6b537332182bd3c8f642accc5eae577055a4c4,PMC,Host-Directed Antivirals: A Realistic Alternative to Fight Zika Virus,http://dx.doi.org/10.3390/v10090453,PMC6163279,30149598,CC BY,"Zika virus (ZIKV), a mosquito-borne flavivirus, was an almost neglected pathogen until its introduction in the Americas in 2015, where it has been responsible for a threat to global health, causing a great social and sanitary alarm due to its increased virulence, rapid spread, and an association with severe neurological and ophthalmological complications. Currently, no specific antiviral therapy against ZIKV is available, and treatments are palliative and mainly directed toward the relief of symptoms, such as fever and rash, by administering antipyretics, anti-histamines, and fluids for dehydration. Nevertheless, lately, search for antivirals has been a major aim in ZIKV investigations. To do so, screening of libraries from different sources, testing of natural compounds, and repurposing of drugs with known antiviral activity have allowed the identification of several antiviral candidates directed to both viral (structural proteins and enzymes) and cellular elements. Here, we present an updated review of current knowledge about anti-ZIKV strategies, focusing on host-directed antivirals as a realistic alternative to combat ZIKV infection.",2018 Aug 24,"['Saiz, Juan-Carlos', 'de Oya, Nereida Jiménez', 'Blázquez, Ana-Belén', 'Escribano-Romero, Estela', 'Martín-Acebes, Miguel A.']",Viruses,,,True
007618ad76a3548195ab5d11c1e2459931c91cd1,PMC,Monocytes and Macrophages as Viral Targets and Reservoirs,http://dx.doi.org/10.3390/ijms19092821,PMC6163364,30231586,CC BY,"Viruses manipulate cell biology to utilize monocytes/macrophages as vessels for dissemination, long-term persistence within tissues and virus replication. Viruses enter cells through endocytosis, phagocytosis, macropinocytosis or membrane fusion. These processes play important roles in the mechanisms contributing to the pathogenesis of these agents and in establishing viral genome persistence and latency. Upon viral infection, monocytes respond with an elevated expression of proinflammatory signalling molecules and antiviral responses, as is shown in the case of the influenza, Chikungunya, human herpes and Zika viruses. Human immunodeficiency virus initiates acute inflammation on site during the early stages of infection but there is a shift of M1 to M2 at the later stages of infection. Cytomegalovirus creates a balance between pro- and anti-inflammatory processes by inducing a specific phenotype within the M1/M2 continuum. Despite facilitating inflammation, infected macrophages generally display abolished apoptosis and restricted cytopathic effect, which sustains the virus production. The majority of viruses discussed in this review employ monocytes/macrophages as a repository but certain viruses use these cells for productive replication. This review focuses on viral adaptations to enter monocytes/macrophages, immune escape, reprogramming of infected cells and the response of the host cells.",2018 Sep 18,"['Nikitina, Ekaterina', 'Larionova, Irina', 'Choinzonov, Evgeniy', 'Kzhyshkowska, Julia']",Int J Mol Sci,,,True
2bc2fe97aaf88704800806bac58b85cfdc39a6e2,PMC,Detection and Characterization of Distinct Alphacoronaviruses in Five Different Bat Species in Denmark,http://dx.doi.org/10.3390/v10090486,PMC6163574,30208582,CC BY,"Bat populations harbour a multitude of viruses; some of these are pathogenic or potentially pathogenic in other animals or humans. Therefore, it is important to monitor the populations and characterize these viruses. In this study, the presence of coronaviruses (CoVs) in different species of Danish bats was investigated using active surveillance at different geographical locations in Denmark. Faecal samples were screened for the presence of CoVs using pan-CoV real-time RT-PCR assays. The amplicons, obtained from five different species of bats, were sequenced. Phylogenetic analysis revealed a species-specific clustering with the samples from Myotis daubentonii, showing a close resemblance to coronavirus sequences obtained from the same species of bat in Germany and the United Kingdom. Our results show, for the first time, that multiple, distinct alphacoronaviruses are present in the Danish bat populations.",2018 Sep 11,"['Lazov, Christina M.', 'Chriél, Mariann', 'Baagøe, Hans J.', 'Fjederholt, Esben', 'Deng, Yu', 'Kooi, Engbert A.', 'Belsham, Graham J.', 'Bøtner, Anette', 'Rasmussen, Thomas Bruun']",Viruses,,,True
42145eff1cc724f8e5ad1a8e04cc421512d8ec7a,PMC,S1 Subunit of Spike Protein from a Current Highly Virulent Porcine Epidemic Diarrhea Virus Is an Important Determinant of Virulence in Piglets,http://dx.doi.org/10.3390/v10090467,PMC6163780,30200258,CC BY,"Base on the sequence of S genes, which encode spike proteins, we previously identified three different types (North American, S INDEL, and S large-DEL types) of porcine epidemic diarrhea virus (PEDV) that have re-emerged in Japan since 2013. Based on experimental infections with the North American and S large-DEL types, we also hypothesized that PEDV virulence may be linked to the S1 subunit of the S protein. To test this hypothesis, we have now assayed in gnotobiotic piglets various recombinant PEDVs generated by reverse genetics. Piglets inoculated with CV777 maintained in National Institute of Animal Health, along with piglets infected with a recombinant form of the same virus, developed subclinical to mild diarrhea. In contrast, severe watery diarrhea, dehydration, weight loss, astasia, and high mortality were observed in piglets inoculated with recombinant strains in which the S gene was partially or fully replaced with corresponding sequences from the highly virulent Japanese PEDV isolate OKN-1/JPN/2013. Indeed, symptoms resembled those in piglets inoculated with the OKN-1/JPN/2013, and were especially pronounced in younger piglets. Collectively, the data demonstrate that the S1 subunit of the S protein is an important determinant of PEDV virulence, and advance development of new vaccine candidate.",2018 Aug 30,"['Suzuki, Tohru', 'Terada, Yutaka', 'Enjuanes, Luis', 'Ohashi, Seiichi', 'Kamitani, Wataru']",Viruses,,,True
8cf02f23f08f2b7c8b0e83dcc85d080f9c1cf615,PMC,The Oakville Oil Refinery Closure and Its Influence on Local Hospitalizations: A Natural Experiment on Sulfur Dioxide,http://dx.doi.org/10.3390/ijerph15092029,PMC6163796,30227660,CC BY,"Background: An oil refinery in Oakville, Canada, closed over 2004–2005, providing an opportunity for a natural experiment to examine the effects on oil refinery-related air pollution and residents’ health. Methods: Environmental and health data were collected for the 16 years around the refinery closure. Toronto (2.5 million persons) and the Greater Toronto Area (GTA, 6.3 million persons) were used as control and reference populations, respectively, for Oakville (160,000 persons). We compared sulfur dioxide and age- and season-standardized hospitalizations, considering potential factors such as changes in demographics, socio-economics, drug prescriptions, and environmental variables. Results: The closure of the refinery eliminated 6000 tons/year of SO(2) emissions, with an observed reduction of 20% in wind direction-adjusted ambient concentrations in Oakville. After accounting for trends, a decrease in cold-season peak-centered respiratory hospitalizations was observed for Oakville (reduction of 2.2 cases/1000 persons per year, [Formula: see text]) but not in Toronto (p = 0.856) and the GTA (p = 0.334). The reduction of respiratory hospitalizations in Oakville post closure appeared to have no observed link to known confounders or effect modifiers. Conclusion: The refinery closure allowed an assessment of the change in community health. This natural experiment provides evidence that a reduction in emissions was associated with improvements in population health. This study design addresses the impact of a removed source of air pollution.",2018 Sep 17,"['Burr, Wesley S.', 'Dales, Robert', 'Liu, Ling', 'Stieb, Dave', 'Smith-Doiron, Marc', 'Jovic, Branka', 'Kauri, Lisa Marie', 'Shin, Hwashin Hyun']",Int J Environ Res Public Health,,,True
1b1b133fc211d0bf8af604d58bedafd5fac7cde9,PMC,Infectious Bronchitis Virus Nonstructural Protein 4 Alone Induces Membrane Pairing,http://dx.doi.org/10.3390/v10090477,PMC6163833,30200673,CC BY,"Positive-strand RNA viruses, such as coronaviruses, induce cellular membrane rearrangements during replication to form replication organelles allowing for efficient viral RNA synthesis. Infectious bronchitis virus (IBV), a pathogenic avian Gammacoronavirus of significant importance to the global poultry industry, has been shown to induce the formation of double membrane vesicles (DMVs), zippered endoplasmic reticulum (zER) and tethered vesicles, known as spherules. These membrane rearrangements are virally induced; however, it remains unclear which viral proteins are responsible. In this study, membrane rearrangements induced when expressing viral non-structural proteins (nsps) from two different strains of IBV were compared. Three non-structural transmembrane proteins, nsp3, nsp4, and nsp6, were expressed in cells singularly or in combination and the effects on cellular membranes investigated using electron microscopy and electron tomography. In contrast to previously studied coronaviruses, IBV nsp4 alone is necessary and sufficient to induce membrane pairing; however, expression of the transmembrane proteins together was not sufficient to fully recapitulate DMVs. This indicates that although nsp4 is able to singularly induce membrane pairing, further viral or host factors are required in order to fully assemble IBV replicative structures. This study highlights further differences in the mechanism of membrane rearrangements between members of the coronavirus family.",2018 Sep 6,"['Doyle, Nicole', 'Neuman, Benjamin W.', 'Simpson, Jennifer', 'Hawes, Philippa C.', 'Mantell, Judith', 'Verkade, Paul', 'Alrashedi, Hasan', 'Maier, Helena J.']",Viruses,,,True
1aea04847a4f34625beaf937ca06ff039a5d3a2e,PMC,Virucidal and Synergistic Activity of Polyphenol-Rich Extracts of Seaweeds against Measles Virus,http://dx.doi.org/10.3390/v10090465,PMC6164608,30200234,CC BY,"Although preventable by vaccination, Measles still causes thousands of deaths among young children worldwide. The discovery of new antivirals is a good approach to control new outbreaks that cause such death. In this study, we tested the antiviral activity against Measles virus (MeV) of Polyphenol-rich extracts (PPs) coming from five seaweeds collected and cultivated in Mexico. An MTT assay was performed to determine cytotoxicity effect, and antiviral activity was measured by syncytia reduction assay and confirmed by qPCR. PPs from Ecklonia arborea (formerly Eisenia arborea, Phaeophyceae) and Solieria filiformis (Rhodophyta) showed the highest Selectivity Index (SI), >3750 and >576.9 respectively. Both PPs extracts were selected to the subsequent experiments owing to their high efficacy and low cytotoxicity compared with ribavirin (SI of 11.57). The combinational effect of PPs with sulphated polysaccharides (SPs) and ribavirin were calculated by using Compusyn software. Synergistic activity was observed by combining both PPs with low concentrations of Solieria filiformis SPs (0.01 µg/mL). The antiviral activity of the best combinations was confirmed by qPCR. Virucidal assay, time of addition, and viral penetration evaluations suggested that PPs act mainly by inactivating the viral particle. To our knowledge, this is the first report of the virucidal effect of Polyphenol-rich extracts of seaweeds.",2018 Aug 30,"['Morán-Santibañez, Karla', 'Peña-Hernández, Mario A.', 'Cruz-Suárez, Lucia Elizabeth', 'Ricque-Marie, Denis', 'Skouta, Rachid', 'Vasquez, Abimael H.', 'Rodríguez-Padilla, Cristina', 'Trejo-Avila, Laura M.']",Viruses,,,True
874e540a730ee1060365af8d2caa03f537508e33,PMC,A Human DPP4-Knockin Mouse’s Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV,http://dx.doi.org/10.3390/v10090448,PMC6164841,30142928,CC BY,"Infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory illness and has a high mortality rate (~35%). The requirement for the virus to be manipulated in a biosafety level three (BSL-3) facility has impeded development of urgently-needed antiviral agents. Here, we established anovel mouse model by inserting human dipeptidyl peptidase 4 (hDPP4) into the Rosa26 locus using CRISPR/Cas9, resulting in global expression of the transgene in a genetically stable mouse line. The mice were highly susceptible to infection by MERS-CoV clinical strain hCoV-EMC, which induced severe diffuse pulmonary disease in the animals, and could also be infected by an optimized pseudotyped MERS-CoV. Administration of the neutralizing monoclonal antibodies, H111-1 and m336, as well as a fusion inhibitor peptide, HR2P-M2, protected mice from challenge with authentic and pseudotyped MERS-CoV. These results confirmed that the hDPP4-knockin mouse is a novel model for studies of MERS-CoV pathogenesis and anti-MERS-CoV antiviral agents in BSL-3 and BSL-2facilities, respectively.",2018 Aug 23,"['Fan, Changfa', 'Wu, Xi', 'Liu, Qiang', 'Li, Qianqian', 'Liu, Susu', 'Lu, Jianjun', 'Yang, Yanwei', 'Cao, Yuan', 'Huang, Weijin', 'Liang, Chunnan', 'Ying, Tianlei', 'Jiang, Shibo', 'Wang, Youchun']",Viruses,,,True
87b95e2ed40ecd0986593b1c5b89861cfdf767eb,PMC,A Human DPP4-Knockin Mouse’s Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV,http://dx.doi.org/10.3390/v10090448,PMC6164841,30142928,CC BY,"Infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory illness and has a high mortality rate (~35%). The requirement for the virus to be manipulated in a biosafety level three (BSL-3) facility has impeded development of urgently-needed antiviral agents. Here, we established anovel mouse model by inserting human dipeptidyl peptidase 4 (hDPP4) into the Rosa26 locus using CRISPR/Cas9, resulting in global expression of the transgene in a genetically stable mouse line. The mice were highly susceptible to infection by MERS-CoV clinical strain hCoV-EMC, which induced severe diffuse pulmonary disease in the animals, and could also be infected by an optimized pseudotyped MERS-CoV. Administration of the neutralizing monoclonal antibodies, H111-1 and m336, as well as a fusion inhibitor peptide, HR2P-M2, protected mice from challenge with authentic and pseudotyped MERS-CoV. These results confirmed that the hDPP4-knockin mouse is a novel model for studies of MERS-CoV pathogenesis and anti-MERS-CoV antiviral agents in BSL-3 and BSL-2facilities, respectively.",2018 Aug 23,"['Fan, Changfa', 'Wu, Xi', 'Liu, Qiang', 'Li, Qianqian', 'Liu, Susu', 'Lu, Jianjun', 'Yang, Yanwei', 'Cao, Yuan', 'Huang, Weijin', 'Liang, Chunnan', 'Ying, Tianlei', 'Jiang, Shibo', 'Wang, Youchun']",Viruses,,,False
1399e34d62b515e482ccde6c4cae500b19546909,PMC,Novel Flu Viruses in Bats and Cattle: “Pushing the Envelope” of Influenza Infection,http://dx.doi.org/10.3390/vetsci5030071,PMC6165133,30082582,CC BY,"Influenza viruses are among the major infectious disease threats of animal and human health. This review examines the recent discovery of novel influenza viruses in bats and cattle, the evolving complexity of influenza virus host range including the ability to cross species barriers and geographic boundaries, and implications to animal and human health.",2018 Aug 6,"['Kuchipudi, Suresh V.', 'Nissly, Ruth H.']",Vet Sci,,,True
daf2e3a8a879ec122b6d89903a43d18890638015,PMC,The Current Status of the Pharmaceutical Potential of Juniperus L. Metabolites,http://dx.doi.org/10.3390/medicines5030081,PMC6165314,30065158,CC BY,"Background: Plants and their derived natural compounds possess various biological and therapeutic properties, which turns them into an increasing topic of interest and research. Juniperus genus is diverse in species, with several traditional medicines reported, and rich in natural compounds with potential for development of new drugs. Methods: The research for this review were based in the Scopus and Web of Science databases using terms combining Juniperus, secondary metabolites names, and biological activities. This is not an exhaustive review of Juniperus compounds with biological activities, but rather a critical selection taking into account the following criteria: (i) studies involving the most recent methodologies for quantitative evaluation of biological activities; and (ii) the compounds with the highest number of studies published in the last four years. Results: From Juniperus species, several diterpenes, flavonoids, and one lignan were emphasized taking into account their level of activity against several targets. Antitumor activity is by far the most studied, being followed by antibacterial and antiviral activities. Deoxypodophyllotoxin and one dehydroabietic acid derivative appears to be the most promising lead compounds. Conclusions: This review demonstrates the Juniperus species value as a source of secondary metabolites with relevant pharmaceutical potential.",2018 Jul 31,"['Tavares, Wilson R.', 'Seca, Ana M. L.']",Medicines (Basel),,,True
dce34f36e8a1d8b4692c1e54852d6942da5d065a,PMC,Caerin1.1 Suppresses the Growth of Porcine Epidemic Diarrhea Virus In Vitro via Direct Binding to the Virus,http://dx.doi.org/10.3390/v10090507,PMC6165370,30231560,CC BY,"Porcine epidemic diarrhea (PED) has re-emerged in recent years and has already caused huge economic losses to the porcine industry all over the world. Therefore, it is urgent for us to find out efficient ways to prevent and control this disease. In this study, the antiviral activity of a cationic amphibian antimicrobial peptide Caerin1.1 against porcine epidemic diarrhea virus (PEDV) was evaluated by an in vitro system using Vero cells. We found that even at a very low concentration, Caerin1.1 has the ability to destroy the integrity of the virus particles to block the release of the viruses, resulting in a considerable decrease in PEDV infections. In addition, Caerin1.1 showed powerful antiviral activity without interfering with the binding progress between PEDV and the receptor of the cells, therefore, it could be used as a potential antiviral drug or as a microbicide compound for prevention and control of PEDV.",2018 Sep 18,"['Guo, Nan', 'Zhang, Bingzhou', 'Hu, Han', 'Ye, Shiyi', 'Chen, Fangzhou', 'Li, Zhonghua', 'Chen, Pin', 'Wang, Chunmei', 'He, Qigai']",Viruses,,,True
91565229659527cb4c0a635614b5add5980a4b59,PMC,Host Shutoff in Influenza A Virus: Many Means to an End,http://dx.doi.org/10.3390/v10090475,PMC6165434,30189604,CC BY,"Influenza A virus carries few of its own proteins, but uses them effectively to take control of the infected cells and avoid immune responses. Over the years, host shutoff, the widespread down-regulation of host gene expression, has emerged as a key process that contributes to cellular takeover in infected cells. Interestingly, multiple mechanisms of host shutoff have been described in influenza A virus, involving changes in translation, RNA synthesis and stability. Several viral proteins, notably the non-structural protein NS1, the RNA-dependent RNA polymerase and the endoribonuclease PA-X have been implicated in host shutoff. This multitude of host shutoff mechanisms indicates that host shutoff is an important component of the influenza A virus replication cycle. Here we review the various mechanisms of host shutoff in influenza A virus and the evidence that they contribute to immune evasion and/or viral replication. We also discuss what the purpose of having multiple mechanisms may be.",2018 Sep 5,"['Levene, Rachel Emily', 'Gaglia, Marta Maria']",Viruses,,,True
16874a8b95e04383b0ee7049220a36354ffab2ea,PMC,Inhibition of Homophilic Interactions and Ligand Binding of the Receptor for Advanced Glycation End Products by Heparin and Heparin-Related Carbohydrate Structures,http://dx.doi.org/10.3390/medicines5030079,PMC6165534,30061484,CC BY,"Background: Heparin and heparin-related sulphated carbohydrates inhibit ligand binding of the receptor for advanced glycation end products (RAGE). Here, we have studied the ability of heparin to inhibit homophilic interactions of RAGE in living cells and studied how heparin related structures interfere with RAGE–ligand interactions. Methods: Homophilic interactions of RAGE were studied with bead aggregation and living cell protein-fragment complementation assays. Ligand binding was analyzed with microwell binding and chromatographic assays. Cell surface advanced glycation end product binding to RAGE was studied using PC3 cell adhesion assay. Results: Homophilic binding of RAGE was mediated by V(1)- and modulated by C(2)-domain in bead aggregation assay. Dimerisation of RAGE on the living cell surface was inhibited by heparin. Sulphated K5 carbohydrate fragments inhibited RAGE binding to amyloid β-peptide and HMGB1. The inhibition was dependent on the level of sulfation and the length of the carbohydrate backbone. α-d-Glucopyranosiduronic acid (glycyrrhizin) inhibited RAGE binding to advanced glycation end products in PC3 cell adhesion and protein binding assays. Further, glycyrrhizin inhibited HMGB1 and HMGB1 A-box binding to heparin. Conclusions: Our results show that K5 polysaccharides and glycyrrhizin are promising candidates for RAGE targeting drug development.",2018 Jul 30,"['Rouhiainen, Ari', 'Nykänen, Niko-Petteri', 'Kuja-Panula, Juha', 'Vanttola, Päivi', 'Huttunen, Henri J.', 'Rauvala, Heikki']",Medicines (Basel),,,True
b0ae17e124d5aff160a564dd700ff9d5ee31578a,PMC,Inflammasome: A Double-Edged Sword in Liver Diseases,http://dx.doi.org/10.3389/fimmu.2018.02201,PMC6167446,30319645,CC BY,"Inflammasomes have emerged as critical innate sensors of host immune that defense against pathogen infection, metabolism syndrome, cellular stress and cancer metastasis in the liver. The assembly of inflammasome activates caspase-1, which promotes the maturation of interleukin-1β (IL-1β) and interleukin-18 (IL-18), and initiates pyroptotic cell death (pyroptosis). IL-18 exerts pleiotropic effects on hepatic NK cells, priming FasL-mediated cytotoxicity, and interferon-γ (IFN-γ)-dependent responses to prevent the development of liver diseases. However, considerable attention has been attracted to the pathogenic role of inflammasomes in various acute and chronic liver diseases, including viral hepatitis, nanoparticle-induced liver injury, alcoholic and non-alcoholic steatohepatitis. In this review, we summarize the latest advances on the physiological and pathological roles of inflammasomes for further development of inflammasome-based therapeutic strategies for human liver diseases.",2018 Sep 25,"['Luan, Jingyun', 'Ju, Dianwen']",Front Immunol,,,True
362ff59c268fdb40d5a9689c370beca4f2a16d66,PMC,"Epidemiology of Severe Acute Respiratory Illness and Risk Factors for Influenza Infection and Clinical Severity among Adults in Malawi, 2011–2013",http://dx.doi.org/10.4269/ajtmh.17-0905,PMC6169174,30039785,CC BY,"Data on the epidemiology of severe acute respiratory illness (SARI) in adults from low-income, high human immunodeficiency virus (HIV) prevalence African settings are scarce. We conducted adult SARI surveillance in Blantyre, Malawi. From January 2011 to December 2013, individuals aged ≥ 15 years with SARI (both inpatients and outpatients) were enrolled at a large teaching hospital in Blantyre, Malawi. Nasopharyngeal aspirates were tested for influenza and other respiratory viruses by polymerase chain reaction. We estimated hospital-attended influenza-positive SARI incidence rates and assessed factors associated with influenza positivity and clinical severity (Modified Early Warning Score > 4). We enrolled 1,126 SARI cases; 163 (14.5%) were positive for influenza. Human immunodeficiency virus prevalence was 50.3%. Annual incidence of hospital-attended influenza-associated SARI was 9.7–16.8 cases per 100,000 population. Human immunodeficiency virus was associated with a 5-fold greater incidence (incidence rate ratio 4.91, 95% confidence interval [CI]: 3.83–6.32). On multivariable analysis, female gender, as well as recruitment in hot, rainy season (December to March; adjusted odds ratios (aOR): 2.82, 95% CI: 1.57–5.06) and cool, dry season (April to August; aOR: 2.47, 95% CI: 1.35–4.15), was associated with influenza positivity, whereas influenza-positive patients were less likely to be HIV-infected (aOR: 0.59, 95% CI: 0.43–0.80) or have viral coinfection (aOR: 0.51, 95% CI: 0.36–0.73). Human immunodeficiency virus infection (aOR: 1.86; 95% CI: 1.35–2.56) and recruitment in hot, rainy season (aOR: 4.98, 95% CI: 3.17–7.81) were independently associated with clinical severity. In this high HIV prevalence population, influenza was associated with nearly 15% of hospital-attended SARI. Human immunodeficiency virus infection is an important risk factor for clinical severity in all-cause and influenza-associated SARI. Expanded access to HIV testing and antiretroviral treatment, as well as targeted influenza vaccination, may reduce the burden of SARI in Malawi and other high HIV prevalence settings.",2018 Sep 23,"['Ho, Antonia', 'Mallewa, Jane', 'Peterson, Ingrid', 'SanJoaquin, Miguel', 'Garg, Shikha', 'Bar-Zeev, Naor', 'Menyere, Mavis', 'Alaerts, Maaike', 'Mapurisa, Gugulethu', 'Chilombe, Moses', 'Nyirenda, Mulinda', 'Lalloo, David G.', 'Rothe, Camilla', 'Widdowson, Marc-Alain', 'McMorrow, Meredith', 'French, Neil', 'Everett, Dean', 'Heyderman, Robert S.']",Am J Trop Med Hyg,,,True
9503694069cf157e33e29033469edc8d1794a35e,PMC,Accounting for Programmed Ribosomal Frameshifting in the Computation of Codon Usage Bias Indices,http://dx.doi.org/10.1534/g3.118.200185,PMC6169388,30111621,CC BY,"Experimental evidence shows that synonymous mutations can have important consequences on genetic fitness. Many organisms display codon usage bias (CUB), where synonymous codons that are translated into the same amino acid appear with distinct frequency. Within genomes, CUB is thought to arise from selection for translational efficiency and accuracy, termed the translational efficiency hypothesis (TEH). Indeed, CUB indices correlate with protein expression levels, which is widely interpreted as evidence for translational selection. However, these tests neglect -1 programmed ribosomal frameshifting (-1 PRF), an important translational disruption effect found across all organisms of the tree of life. Genes that contain -1 PRF signals should cost more to express than genes without. Thus, CUB indices that do not consider -1 PRF may overestimate genes’ true adaptation to translational efficiency and accuracy constraints. Here, we first investigate whether -1 PRF signals do indeed carry such translational cost. We then propose two corrections for CUB indices for genes containing -1 PRF signals. We retest the TEH in Saccharomyces cerevisiae under these corrections. We find that the correlation between corrected CUB index and protein expression remains intact for most levels of uniform -1 PRF efficiencies, and tends to increase when these efficiencies decline with protein expression. We conclude that the TEH is strengthened and that -1 PRF events constitute a promising and useful tool to examine the relationships between CUB and selection for translation efficiency and accuracy.",2018 Aug 23,"['Garcia, Victor', 'Zoller, Stefan', 'Anisimova, Maria']",G3 (Bethesda),,,True
517aa0b6c174589d7183d73b1ce2f3787d86e369,PMC,Epidemiology and Immune Pathogenesis of Viral Sepsis,http://dx.doi.org/10.3389/fimmu.2018.02147,PMC6170629,30319615,CC BY,"Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis can be caused by a broad range of pathogens; however, bacterial infections represent the majority of sepsis cases. Up to 42% of sepsis presentations are culture negative, suggesting a non-bacterial cause. Despite this, diagnosis of viral sepsis remains very rare. Almost any virus can cause sepsis in vulnerable patients (e.g., neonates, infants, and other immunosuppressed groups). The prevalence of viral sepsis is not known, nor is there enough information to make an accurate estimate. The initial standard of care for all cases of sepsis, even those that are subsequently proven to be culture negative, is the immediate use of broad-spectrum antibiotics. In the absence of definite diagnostic criteria for viral sepsis, or at least to exclude bacterial sepsis, this inevitably leads to unnecessary antimicrobial use, with associated consequences for antimicrobial resistance, effects on the host microbiome and excess healthcare costs. It is important to understand non-bacterial causes of sepsis so that inappropriate treatment can be minimised, and appropriate treatments can be developed to improve outcomes. In this review, we summarise what is known about viral sepsis, its most common causes, and how the immune responses to severe viral infections can contribute to sepsis. We also discuss strategies to improve our understanding of viral sepsis, and ways we can integrate this new information into effective treatment.",2018 Sep 27,"['Lin, Gu-Lung', 'McGinley, Joseph P.', 'Drysdale, Simon B.', 'Pollard, Andrew J.']",Front Immunol,,,True
f3a378151096d647f4982841888e944c7aa031b1,PMC,Early Growth Response Gene-1 Suppresses Foot-and-Mouth Disease Virus Replication by Enhancing Type I Interferon Pathway Signal Transduction,http://dx.doi.org/10.3389/fmicb.2018.02326,PMC6170816,30319594,CC BY,"Early growth response gene-1 (EGR1) is a multifunctional transcription factor that is implicated in viral infection. In this study, we observed that foot-and-mouth disease virus (FMDV) infection significantly triggered EGR1 expression. Overexpression of EGR1 suppressed FMDV replication in porcine cells, and knockdown of EGR1 considerably promoted FMDV replication. A previously reported FMDV mutant virus (with two amino acids mutations in SAP domain) that displays a strong type I interferon (IFN) induction activity was used in this study. We found that SAP mutant FMDV infection induced a higher expression of EGR1 than wildtype FMDV infection, and also triggered higher IFN-β and IFN-stimulated genes (ISGs) expression than wildtype FMDV infection. This implied a link between EGR1 and type I IFN signaling. Further study showed that overexpression of EGR1 resulted in Sendai virus (SeV)-induced IFN-stimulated response element (ISRE) and NF-κB promoter activation. In addition, the SeV-induced ISGs expression was impaired in EGR1 knockdown cells. EGR1 upregulation promoted type I IFN signaling activation and suppressed FMDV and Seneca Valley virus replication. Suppression of the transcriptional activity of EGR1 did not affect its antiviral effect against FMDV. This study reveals a new mechanism evolved by EGR1 to enhance type I IFN signaling and suppress FMDV replication.",2018 Sep 27,"['Zhu, Zixiang', 'Du, Xiaoli', 'Li, Pengfei', 'Zhang, Xiangle', 'Yang, Fan', 'Cao, Weijun', 'Tian, Hong', 'Zhang, Keshan', 'Liu, Xiangtao', 'Zheng, Haixue']",Front Microbiol,,,True
aec276f9c340e5be5f9db9264727cbc8606203e3,PMC,Comparative analysis of rodent and small mammal viromes to better understand the wildlife origin of emerging infectious diseases,http://dx.doi.org/10.1186/s40168-018-0554-9,PMC6171170,30285857,CC BY,"BACKGROUND: Rodents represent around 43% of all mammalian species, are widely distributed, and are the natural reservoirs of a diverse group of zoonotic viruses, including hantaviruses, Lassa viruses, and tick-borne encephalitis viruses. Thus, analyzing the viral diversity harbored by rodents could assist efforts to predict and reduce the risk of future emergence of zoonotic viral diseases. RESULTS: We used next-generation sequencing metagenomic analysis to survey for a range of mammalian viral families in rodents and other small animals of the orders Rodentia, Lagomorpha, and Soricomorpha in China. We sampled 3,055 small animals from 20 provinces and then outlined the spectra of mammalian viruses within these individuals and the basic ecological and genetic characteristics of novel rodent and shrew viruses among the viral spectra. Further analysis revealed that host taxonomy plays a primary role and geographical location plays a secondary role in determining viral diversity. Many viruses were reported for the first time with distinct evolutionary lineages, and viruses related to known human or animal pathogens were identified. Phylogram comparison between viruses and hosts indicated that host shifts commonly happened in many different species during viral evolutionary history. CONCLUSIONS: These results expand our understanding of the viromes of rodents and insectivores in China and suggest that there is high diversity of viruses awaiting discovery in these species in Asia. These findings, combined with our previous bat virome data, greatly increase our knowledge of the viral community in wildlife in a densely populated country in an emerging disease hotspot. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40168-018-0554-9) contains supplementary material, which is available to authorized users.",2018 Oct 3,"['Wu, Zhiqiang', 'Lu, Liang', 'Du, Jiang', 'Yang, Li', 'Ren, Xianwen', 'Liu, Bo', 'Jiang, Jinyong', 'Yang, Jian', 'Dong, Jie', 'Sun, Lilian', 'Zhu, Yafang', 'Li, Yuhui', 'Zheng, Dandan', 'Zhang, Chi', 'Su, Haoxiang', 'Zheng, Yuting', 'Zhou, Hongning', 'Zhu, Guangjian', 'Li, Hongying', 'Chmura, Aleksei', 'Yang, Fan', 'Daszak, Peter', 'Wang, Jianwei', 'Liu, Qiyong', 'Jin, Qi']",Microbiome,,,True
863ffba681e73f1174a2949a281340f82ed241e7,PMC,The ADRP domain from a virulent strain of infectious bronchitis virus is not sufficient to confer a pathogenic phenotype to the attenuated Beaudette strain,http://dx.doi.org/10.1099/jgv.0.001098,PMC6171709,29893665,CC BY,"The replicase gene of the coronavirus infectious bronchitis virus (IBV) encodes 15 non-structural proteins (nsps). Nsp 3 is a multi-functional protein containing a conserved ADP-ribose-1″-phosphatase (ADRP) domain. The crystal structures of the domain from two strains of IBV, M41 (virulent) and Beaudette (avirulent), identified a key difference; M41 contains a conserved triple-glycine motif, whilst Beaudette contains a glycine-to-serine mutation that is predicted to abolish ADRP activity. Although ADRP activity has not been formally demonstrated for IBV nsp 3, Beaudette fails to bind ADP-ribose. The role of ADRP in virulence was investigated by generating rIBVs, based on Beaudette, containing either a restored triple-glycine motif or the complete M41 ADRP domain. Replication in vitro was unaffected by the ADRP modifications and the in vivo phenotype of the rIBVs was found to be apathogenic, indicating that restoration of the triple-glycine motif is not sufficient to restore virulence to the apathogenic Beaudette strain.",2018 Aug 12,"['Keep, Sarah', 'Bickerton, Erica', 'Armesto, Maria', 'Britton, Paul']",J Gen Virol,,,True
0a617f5467e92a9a638ee23204247128635e32aa,PMC,Role of extracellular matrix and microenvironment in regulation of tumor growth and LAR-mediated invasion in glioblastoma,http://dx.doi.org/10.1371/journal.pone.0204865,PMC6171904,30286133,CC BY,"The cellular dispersion and therapeutic control of glioblastoma, the most aggressive type of primary brain cancer, depends critically on the migration patterns after surgery and intracellular responses of the individual cancer cells in response to external biochemical cues in the microenvironment. Recent studies have shown that miR-451 regulates downstream molecules including AMPK/CAB39/MARK and mTOR to determine the balance between rapid proliferation and invasion in response to metabolic stress in the harsh tumor microenvironment. Surgical removal of the main tumor is inevitably followed by recurrence of the tumor due to inaccessibility of dispersed tumor cells in normal brain tissue. In order to address this complex process of cell proliferation and invasion and its response to conventional treatment, we propose a mathematical model that analyzes the intracellular dynamics of the miR-451-AMPK- mTOR-cell cycle signaling pathway within a cell. The model identifies a key mechanism underlying the molecular switches between proliferative phase and migratory phase in response to metabolic stress in response to fluctuating glucose levels. We show how up- or down-regulation of components in these pathways affects the key cellular decision to infiltrate or proliferate in a complex microenvironment in the absence and presence of time delays and stochastic noise. Glycosylated chondroitin sulfate proteoglycans (CSPGs), a major component of the extracellular matrix (ECM) in the brain, contribute to the physical structure of the local brain microenvironment but also induce or inhibit glioma invasion by regulating the dynamics of the CSPG receptor LAR as well as the spatiotemporal activation status of resident astrocytes and tumor-associated microglia. Using a multi-scale mathematical model, we investigate a CSPG-induced switch between invasive and non-invasive tumors through the coordination of ECM-cell adhesion and dynamic changes in stromal cells. We show that the CSPG-rich microenvironment is associated with non-invasive tumor lesions through LAR-CSGAG binding while the absence of glycosylated CSPGs induce the critical glioma invasion. We illustrate how high molecular weight CSPGs can regulate the exodus of local reactive astrocytes from the main tumor lesion, leading to encapsulation of non-invasive tumor and inhibition of tumor invasion. These different CSPG conditions also change the spatial profiles of ramified and activated microglia. The complex distribution of CSPGs in the tumor microenvironment can determine the nonlinear invasion behaviors of glioma cells, which suggests the need for careful therapeutic strategies.",2018 Oct 4,"['Kim, Yangjin', 'Kang, Hyunji', 'Powathil, Gibin', 'Kim, Hyeongi', 'Trucu, Dumitru', 'Lee, Wanho', 'Lawler, Sean', 'Chaplain, Mark']",PLoS One,,,True
59c41eef8e1d079fc6d1de1cf07cd989c8456d1c,PMC,Role of extracellular matrix and microenvironment in regulation of tumor growth and LAR-mediated invasion in glioblastoma,http://dx.doi.org/10.1371/journal.pone.0204865,PMC6171904,30286133,CC BY,"The cellular dispersion and therapeutic control of glioblastoma, the most aggressive type of primary brain cancer, depends critically on the migration patterns after surgery and intracellular responses of the individual cancer cells in response to external biochemical cues in the microenvironment. Recent studies have shown that miR-451 regulates downstream molecules including AMPK/CAB39/MARK and mTOR to determine the balance between rapid proliferation and invasion in response to metabolic stress in the harsh tumor microenvironment. Surgical removal of the main tumor is inevitably followed by recurrence of the tumor due to inaccessibility of dispersed tumor cells in normal brain tissue. In order to address this complex process of cell proliferation and invasion and its response to conventional treatment, we propose a mathematical model that analyzes the intracellular dynamics of the miR-451-AMPK- mTOR-cell cycle signaling pathway within a cell. The model identifies a key mechanism underlying the molecular switches between proliferative phase and migratory phase in response to metabolic stress in response to fluctuating glucose levels. We show how up- or down-regulation of components in these pathways affects the key cellular decision to infiltrate or proliferate in a complex microenvironment in the absence and presence of time delays and stochastic noise. Glycosylated chondroitin sulfate proteoglycans (CSPGs), a major component of the extracellular matrix (ECM) in the brain, contribute to the physical structure of the local brain microenvironment but also induce or inhibit glioma invasion by regulating the dynamics of the CSPG receptor LAR as well as the spatiotemporal activation status of resident astrocytes and tumor-associated microglia. Using a multi-scale mathematical model, we investigate a CSPG-induced switch between invasive and non-invasive tumors through the coordination of ECM-cell adhesion and dynamic changes in stromal cells. We show that the CSPG-rich microenvironment is associated with non-invasive tumor lesions through LAR-CSGAG binding while the absence of glycosylated CSPGs induce the critical glioma invasion. We illustrate how high molecular weight CSPGs can regulate the exodus of local reactive astrocytes from the main tumor lesion, leading to encapsulation of non-invasive tumor and inhibition of tumor invasion. These different CSPG conditions also change the spatial profiles of ramified and activated microglia. The complex distribution of CSPGs in the tumor microenvironment can determine the nonlinear invasion behaviors of glioma cells, which suggests the need for careful therapeutic strategies.",2018 Oct 4,"['Kim, Yangjin', 'Kang, Hyunji', 'Powathil, Gibin', 'Kim, Hyeongi', 'Trucu, Dumitru', 'Lee, Wanho', 'Lawler, Sean', 'Chaplain, Mark']",PLoS One,,,True
d54f3fe4cf51fd80a04696c49d4fdc0455b8fe21,PMC,Synthetic viruses—Anything new?,http://dx.doi.org/10.1371/journal.ppat.1007019,PMC6171941,30286176,CC BY,,2018 Oct 4,"Thiel, Volker",PLoS Pathog,,,True
543bb5a781a4069b7239c71dc88ccdadebd085bf,PMC,The papain-like protease determines a virulence trait that varies among members of the SARS-coronavirus species,http://dx.doi.org/10.1371/journal.ppat.1007296,PMC6171950,30248143,CC BY,"SARS-coronavirus (CoV) is a zoonotic agent derived from rhinolophid bats, in which a plethora of SARS-related, conspecific viral lineages exist. Whereas the variability of virulence among reservoir-borne viruses is unknown, it is generally assumed that the emergence of epidemic viruses from animal reservoirs requires human adaptation. To understand the influence of a viral factor in relation to interspecies spillover, we studied the papain-like protease (PLP) of SARS-CoV. This key enzyme drives the early stages of infection as it cleaves the viral polyprotein, deubiquitinates viral and cellular proteins, and antagonizes the interferon (IFN) response. We identified a bat SARS-CoV PLP, which shared 86% amino acid identity with SARS-CoV PLP, and used reverse genetics to insert it into the SARS-CoV genome. The resulting virus replicated like SARS-CoV in Vero cells but was suppressed in IFN competent MA-104 (3.7-fold), Calu-3 (2.6-fold) and human airway epithelial cells (10.3-fold). Using ectopically-expressed PLP variants as well as full SARS-CoV infectious clones chimerized for PLP, we found that a protease-independent, anti-IFN function exists in SARS-CoV, but not in a SARS-related, bat-borne virus. This PLP-mediated anti-IFN difference was seen in primate, human as well as bat cells, thus independent of the host context. The results of this study revealed that coronavirus PLP confers a variable virulence trait among members of the species SARS-CoV, and that a SARS-CoV lineage with virulent PLPs may have pre-existed in the reservoir before onset of the epidemic.",2018 Sep 24,"['Niemeyer, Daniela', 'Mösbauer, Kirstin', 'Klein, Eva M.', 'Sieberg, Andrea', 'Mettelman, Robert C.', 'Mielech, Anna M.', 'Dijkman, Ronald', 'Baker, Susan C.', 'Drosten, Christian', 'Müller, Marcel A.']",PLoS Pathog,,,True
bafffaf17be4302a4a6e79b3f65b9238ab00c258,PMC,Generation of therapeutic antisera for emerging viral infections,http://dx.doi.org/10.1038/s41541-018-0082-4,PMC6173733,30323953,CC BY,"The recent Ebola virus outbreak has highlighted the therapeutic potential of antisera and renewed interest in this treatment approach. While human convalescent sera may not be readily available in the early stages of an outbreak, antisera of animal origin can be produced in a short time frame. Here, we compared adjuvanted virus-like particles (VLP) with recombinant modified vaccinia virus Ankara and vesicular stomatitis virus (VSV), both expressing the Ebola virus antigens. The neutralizing antibody titers of rabbits immunized with adjuvanted VLPs were similar to those immunized with the replication-competent VSV, indicating that presentation of the antigen in its native conformation rather than de novo antigen expression is essential for production of functional antibodies. This approach also yielded high-titer antisera against Nipah virus glycoproteins, illustrating that it is transferable to other virus families. Multiple-step immunoglobulin G purification using a two-step 20–40% ammonium sulfate precipitation followed by protein A affinity chromatography resulted in 90% recovery of functionality and sustained in vivo stability. Adjuvanted VLP-based immunization strategies are thus a promising approach for the rapid generation of therapeutic antisera against emerging infections.",2018 Oct 5,"['Schmidt, Rebecca', 'Beltzig, Lea C.', 'Sawatsky, Bevan', 'Dolnik, Olga', 'Dietzel, Erik', 'Krähling, Verena', 'Volz, Asisa', 'Sutter, Gerd', 'Becker, Stephan', 'von Messling, Veronika']",NPJ Vaccines,,,True
9abc1a92424ffc51803613392c22320da59ebfb1,PMC,Quantifying the value of surveillance data for improving model predictions of lymphatic filariasis elimination,http://dx.doi.org/10.1371/journal.pntd.0006674,PMC6175292,30296266,CC BY,"BACKGROUND: Mathematical models are increasingly being used to evaluate strategies aiming to achieve the control or elimination of parasitic diseases. Recently, owing to growing realization that process-oriented models are useful for ecological forecasts only if the biological processes are well defined, attention has focused on data assimilation as a means to improve the predictive performance of these models. METHODOLOGY AND PRINCIPAL FINDINGS: We report on the development of an analytical framework to quantify the relative values of various longitudinal infection surveillance data collected in field sites undergoing mass drug administrations (MDAs) for calibrating three lymphatic filariasis (LF) models (EPIFIL, LYMFASIM, and TRANSFIL), and for improving their predictions of the required durations of drug interventions to achieve parasite elimination in endemic populations. The relative information contribution of site-specific data collected at the time points proposed by the WHO monitoring framework was evaluated using model-data updating procedures, and via calculations of the Shannon information index and weighted variances from the probability distributions of the estimated timelines to parasite extinction made by each model. Results show that data-informed models provided more precise forecasts of elimination timelines in each site compared to model-only simulations. Data streams that included year 5 post-MDA microfilariae (mf) survey data, however, reduced each model’s uncertainty most compared to data streams containing only baseline and/or post-MDA 3 or longer-term mf survey data irrespective of MDA coverage, suggesting that data up to this monitoring point may be optimal for informing the present LF models. We show that the improvements observed in the predictive performance of the best data-informed models may be a function of temporal changes in inter-parameter interactions. Such best data-informed models may also produce more accurate predictions of the durations of drug interventions required to achieve parasite elimination. SIGNIFICANCE: Knowledge of relative information contributions of model only versus data-informed models is valuable for improving the usefulness of LF model predictions in management decision making, learning system dynamics, and for supporting the design of parasite monitoring programmes. The present results further pinpoint the crucial need for longitudinal infection surveillance data for enhancing the precision and accuracy of model predictions of the intervention durations required to achieve parasite elimination in an endemic location.",2018 Oct 8,"['Michael, Edwin', 'Sharma, Swarnali', 'Smith, Morgan E.', 'Touloupou, Panayiota', 'Giardina, Federica', 'Prada, Joaquin M.', 'Stolk, Wilma A.', 'Hollingsworth, Deirdre', 'de Vlas, Sake J.']",PLoS Negl Trop Dis,,,True
36c09af15d4a614f954aae5a5f8a4199f1ff8b2f,PMC,Monitoring the age-specificity of measles transmissions during 2009-2016 in Southern China,http://dx.doi.org/10.1371/journal.pone.0205339,PMC6175510,30296273,CC BY,"BACKGROUND: Despite several immunization efforts, China saw a resurgence of measles in 2012. Monitoring of transmissions of individuals from different age groups could offer information that would be valuable for planning adequate disease control strategies. We compared the age-specific effective reproductive numbers (R) of measles during 2009–2016 in Guangdong, China. METHODS: We estimated the age-specific R values for 7 age groups: 0–8 months, 9–18 months, 19 months to 6 years, 7–15 years, 16–25 years, 26–45 years, and ≥46 years adapting the contact matrix of China. The daily numbers of laboratory and clinically confirmed cases reported to the Center for Disease Control and Prevention of Guangdong were used. RESULTS: The peak R values of the entire population were above unity from 2012 to 2016, indicating the persistence of measles in the population. In general, children aged 0–6 years and adults aged 26–45 years had larger values of R when comparing with other age groups after 2012. While the peaks of R values for children aged 0–6 years dropped steadily after 2013, the peaks of R values for adults aged 26–45 years kept at a high range every year. CONCLUSIONS: Although the provincial supplementary immunization activities (SIAs) conducted in 2009 and 2010 were able to reduce the transmissions from 2009 to 2011, larger values of R for children aged 0–6 years were observed after 2012, indicating that the benefits of the SIAs were short-lived. In addition, the transmissions from adults aged between 26 and 45 years increased over time. Disease control strategies should target children and adult groups that carry high potential for measles transmission.",2018 Oct 8,"['Chong, Ka Chun', 'Hu, Pei', 'Lau, Steven', 'Jia, Katherine Min', 'Liang, Wenjia', 'Wang, Maggie Haitian', 'Zee, Benny Chung Ying', 'Sun, Riyang', 'Zheng, Huizhen']",PLoS One,,,True
3b6745fa6be6fd2681d3765e918f16a3151fe90d,PMC,Monitoring the age-specificity of measles transmissions during 2009-2016 in Southern China,http://dx.doi.org/10.1371/journal.pone.0205339,PMC6175510,30296273,CC BY,"BACKGROUND: Despite several immunization efforts, China saw a resurgence of measles in 2012. Monitoring of transmissions of individuals from different age groups could offer information that would be valuable for planning adequate disease control strategies. We compared the age-specific effective reproductive numbers (R) of measles during 2009–2016 in Guangdong, China. METHODS: We estimated the age-specific R values for 7 age groups: 0–8 months, 9–18 months, 19 months to 6 years, 7–15 years, 16–25 years, 26–45 years, and ≥46 years adapting the contact matrix of China. The daily numbers of laboratory and clinically confirmed cases reported to the Center for Disease Control and Prevention of Guangdong were used. RESULTS: The peak R values of the entire population were above unity from 2012 to 2016, indicating the persistence of measles in the population. In general, children aged 0–6 years and adults aged 26–45 years had larger values of R when comparing with other age groups after 2012. While the peaks of R values for children aged 0–6 years dropped steadily after 2013, the peaks of R values for adults aged 26–45 years kept at a high range every year. CONCLUSIONS: Although the provincial supplementary immunization activities (SIAs) conducted in 2009 and 2010 were able to reduce the transmissions from 2009 to 2011, larger values of R for children aged 0–6 years were observed after 2012, indicating that the benefits of the SIAs were short-lived. In addition, the transmissions from adults aged between 26 and 45 years increased over time. Disease control strategies should target children and adult groups that carry high potential for measles transmission.",2018 Oct 8,"['Chong, Ka Chun', 'Hu, Pei', 'Lau, Steven', 'Jia, Katherine Min', 'Liang, Wenjia', 'Wang, Maggie Haitian', 'Zee, Benny Chung Ying', 'Sun, Riyang', 'Zheng, Huizhen']",PLoS One,,,False
53c2175f0a8f81a5f88263287a3e9b4fb2cde353,PMC,Monitoring the age-specificity of measles transmissions during 2009-2016 in Southern China,http://dx.doi.org/10.1371/journal.pone.0205339,PMC6175510,30296273,CC BY,"BACKGROUND: Despite several immunization efforts, China saw a resurgence of measles in 2012. Monitoring of transmissions of individuals from different age groups could offer information that would be valuable for planning adequate disease control strategies. We compared the age-specific effective reproductive numbers (R) of measles during 2009–2016 in Guangdong, China. METHODS: We estimated the age-specific R values for 7 age groups: 0–8 months, 9–18 months, 19 months to 6 years, 7–15 years, 16–25 years, 26–45 years, and ≥46 years adapting the contact matrix of China. The daily numbers of laboratory and clinically confirmed cases reported to the Center for Disease Control and Prevention of Guangdong were used. RESULTS: The peak R values of the entire population were above unity from 2012 to 2016, indicating the persistence of measles in the population. In general, children aged 0–6 years and adults aged 26–45 years had larger values of R when comparing with other age groups after 2012. While the peaks of R values for children aged 0–6 years dropped steadily after 2013, the peaks of R values for adults aged 26–45 years kept at a high range every year. CONCLUSIONS: Although the provincial supplementary immunization activities (SIAs) conducted in 2009 and 2010 were able to reduce the transmissions from 2009 to 2011, larger values of R for children aged 0–6 years were observed after 2012, indicating that the benefits of the SIAs were short-lived. In addition, the transmissions from adults aged between 26 and 45 years increased over time. Disease control strategies should target children and adult groups that carry high potential for measles transmission.",2018 Oct 8,"['Chong, Ka Chun', 'Hu, Pei', 'Lau, Steven', 'Jia, Katherine Min', 'Liang, Wenjia', 'Wang, Maggie Haitian', 'Zee, Benny Chung Ying', 'Sun, Riyang', 'Zheng, Huizhen']",PLoS One,,,False
348e9d5eb25a7d8b2b9597d7a24642eb67abc034,PMC,Antibiotic use for community-acquired pneumonia in neonates and children: WHO evidence review,http://dx.doi.org/10.1080/20469047.2017.1409455,PMC6176769,29790844,CC BY,"Background Pneumonia is the most common cause of death in children worldwide, accounting for 15% of all deaths of children under 5 years of age. This review summarises the evidence for the empirical antibiotic treatment of community-acquired pneumonia in neonates and children and puts emphasis on publications since the release of the previous WHO Evidence Summary report published in 2014. Methods A systematic search for systematic reviews and meta-analyses of antibiotic therapy for community-acquired pneumonia was conducted between 1 January 2013 and 10 November 2016. Results The optimal dosing recommendation for amoxicillin remains unclear with limited pharmacological and clinical evidence. There is limited evidence from surveillance to indicate whether amoxicillin or broader spectrum antibiotics (e.g. third-generation cephalosporins) are being used most commonly for paediatric CAP in different WHO regions. Data are lacking on clinical efficacy in the context of pneumococcal, staphylococcal and mycoplasma disease and the relative contributions of varying first-line and step-down options to the selection of such resistance. Conclusion Further pragmatic trials are required to optimise management of hospitalised children with severe and very severe pneumonia.",2018 May 23,"['Mathur, Shrey', 'Fuchs, Aline', 'Bielicki, Julia', 'Van Den Anker, Johannes', 'Sharland, Mike']",Paediatr Int Child Health,,,True
3cffdde62288c2bedae29c7291a5304f9cb9279b,PMC,Insights into the genetic and host adaptability of emerging porcine circovirus 3,http://dx.doi.org/10.1080/21505594.2018.1492863,PMC6177243,29973122,CC BY,"Porcine circovirus 3 (PCV3) was found to be associated with reproductive disease in pigs, and since its first identification in the United States, it subsequently spread worldwide, especially in China, where it might pose a potential threat to the porcine industry. However, no exhaustive analysis was performed to understand its evolution in the prospect of codon usage pattern. Here, we performed a deep codon usage analysis of PCV3. PCV3 sequences were classified into two clades: PCV3a and PCV3b, confirmed by principal component analysis. Additionally, the degree of codon usage bias of PCV3 was slightly low as inferred from the analysis of the effective number of codons. The codon usage pattern was mainly affected by natural selection, but there was a co-effect of mutation pressure and dinucleotide frequency. Moreover, based on similarity index analysis, codon adaptation index analysis and relative codon deoptimization index analysis, we found that PCV3 might pose a potential risk to public health though with unknow pathogenicity. In conclusion, this work reinforces the systematic understanding of the evolution of PCV3, which was reflected by the codon usage patterns and fitness of this novel emergent virus.",2018 Aug 24,"['Li, Gairu', 'Wang, Huijuan', 'Wang, Shilei', 'Xing, Gang', 'Zhang, Cheng', 'Zhang, Wenyan', 'Liu, Jie', 'Zhang, Junyan', 'Su, Shuo', 'Zhou, Jiyong']",Virulence,,,True
14c01878f60c1006ff553c43ef46331034bc1751,PMC,Insights into the genetic and host adaptability of emerging porcine circovirus 3,http://dx.doi.org/10.1080/21505594.2018.1492863,PMC6177243,29973122,CC BY,"Porcine circovirus 3 (PCV3) was found to be associated with reproductive disease in pigs, and since its first identification in the United States, it subsequently spread worldwide, especially in China, where it might pose a potential threat to the porcine industry. However, no exhaustive analysis was performed to understand its evolution in the prospect of codon usage pattern. Here, we performed a deep codon usage analysis of PCV3. PCV3 sequences were classified into two clades: PCV3a and PCV3b, confirmed by principal component analysis. Additionally, the degree of codon usage bias of PCV3 was slightly low as inferred from the analysis of the effective number of codons. The codon usage pattern was mainly affected by natural selection, but there was a co-effect of mutation pressure and dinucleotide frequency. Moreover, based on similarity index analysis, codon adaptation index analysis and relative codon deoptimization index analysis, we found that PCV3 might pose a potential risk to public health though with unknow pathogenicity. In conclusion, this work reinforces the systematic understanding of the evolution of PCV3, which was reflected by the codon usage patterns and fitness of this novel emergent virus.",2018 Aug 24,"['Li, Gairu', 'Wang, Huijuan', 'Wang, Shilei', 'Xing, Gang', 'Zhang, Cheng', 'Zhang, Wenyan', 'Liu, Jie', 'Zhang, Junyan', 'Su, Shuo', 'Zhou, Jiyong']",Virulence,,,False
a647ca891190fdc6954ebb1d68b2758a2c7d6f64,PMC,Staphylococcus aureus colonization and non-influenza respiratory viruses: Interactions and synergism mechanisms,http://dx.doi.org/10.1080/21505594.2018.1504561,PMC6177244,30058450,CC BY,"Viral infections of the respiratory tract can be complicated by bacterial superinfection, resulting in a significantly longer duration of illness and even a fatal outcome. In this review, we focused on interactions between S. aureus and non-influenza viruses. Clinical data evidenced that rhinovirus infection may increase the S. aureus carriage load in humans and its spread. In children, respiratory syncytial virus infection is associated with S. aureus carriage. The mechanisms by which some non-influenza respiratory viruses predispose host cells to S. aureus superinfection can be summarized in three categories: i) modifying expression levels of cellular patterns involved in S. aureus adhesion and/or internalization, ii) inducing S. aureus invasion of epithelial cells due to the disruption of tight junctions, and iii) decreasing S. aureus clearance by altering the immune response. The comprehension of pathways involved in S. aureus-respiratory virus interactions may help developing new strategies of preventive and curative therapy.",2018 Aug 26,"['Morgene, M. Fedy', 'Botelho-Nevers, Elisabeth', 'Grattard, Florence', 'Pillet, Sylvie', 'Berthelot, Philippe', 'Pozzetto, Bruno', 'Verhoeven, Paul O.']",Virulence,,,True
216faa14d038936ecefa54d86fa75335a5f0cb35,PMC,Porcine Reproductive and Respiratory Syndrome Virus strains with Higher Virulence Cause Marked Protein Profile Changes in MARC-145 Cells,http://dx.doi.org/10.1038/s41598-018-32984-0,PMC6177479,30302013,CC BY,"Porcine reproductive and respiratory syndrome is an infectious disease that causes serious economic losses to the swine industry worldwide. To better understand the pathogenesis of the porcine reproductive and respiratory syndrome virus (PRRSV), three PRRSV strains with different molecular markers and virulence were used to infect MARC-145 cells. A total of 1804 proteins were identified, and 233 altered proteins and 72 signaling pathways involved in the proteomic profiling of virus-infected MARC-145 cells increased with the virulence of the PRRSV strain. The three types of viral strains shared a common pathway—the electron transport reaction in mitochondria—in the infected-MARC-145 cells. Moreover, the antisense pathway was the most variable of all significant signaling pathways for the highly virulent SX-1 strain, indicating that this unique pathway may be connected to the high virulence of the SX-1 strain. Our study is the first attempt to provide a proteome profile of MARC-145 cells infected with PRRSV strains with different virulence, and these findings will facilitate a deep understanding of the interactions between this virus and its host.",2018 Oct 9,"['Chen, Zhi', 'Liu, Shaoning', 'Zhang, Shujin', 'Zhang, Yuyu', 'Yu, Jiang', 'Sun, Wenbo', 'Chen, Lei', 'Du, Yijun', 'Wang, Jinbao', 'Li, Yubao', 'Wu, Jiaqiang']",Sci Rep,,,False
21c5b88a655bb1b5b8c3c3cd1dc1aefcf2c75cbd,PMC,Porcine Reproductive and Respiratory Syndrome Virus strains with Higher Virulence Cause Marked Protein Profile Changes in MARC-145 Cells,http://dx.doi.org/10.1038/s41598-018-32984-0,PMC6177479,30302013,CC BY,"Porcine reproductive and respiratory syndrome is an infectious disease that causes serious economic losses to the swine industry worldwide. To better understand the pathogenesis of the porcine reproductive and respiratory syndrome virus (PRRSV), three PRRSV strains with different molecular markers and virulence were used to infect MARC-145 cells. A total of 1804 proteins were identified, and 233 altered proteins and 72 signaling pathways involved in the proteomic profiling of virus-infected MARC-145 cells increased with the virulence of the PRRSV strain. The three types of viral strains shared a common pathway—the electron transport reaction in mitochondria—in the infected-MARC-145 cells. Moreover, the antisense pathway was the most variable of all significant signaling pathways for the highly virulent SX-1 strain, indicating that this unique pathway may be connected to the high virulence of the SX-1 strain. Our study is the first attempt to provide a proteome profile of MARC-145 cells infected with PRRSV strains with different virulence, and these findings will facilitate a deep understanding of the interactions between this virus and its host.",2018 Oct 9,"['Chen, Zhi', 'Liu, Shaoning', 'Zhang, Shujin', 'Zhang, Yuyu', 'Yu, Jiang', 'Sun, Wenbo', 'Chen, Lei', 'Du, Yijun', 'Wang, Jinbao', 'Li, Yubao', 'Wu, Jiaqiang']",Sci Rep,,,True
948028bf6ac0f66ea490a476c599db04fb42a50f,PMC,Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis,http://dx.doi.org/10.1128/mBio.01753-18,PMC6178621,30301856,CC BY,"Acute respiratory distress syndrome (ARDS) is immune-driven pathologies that are observed in severe cases of severe acute respiratory syndrome coronavirus (SARS-CoV) infection. SARS-CoV emerged in 2002 to 2003 and led to a global outbreak of SARS. As with the outcome of human infection, intranasal infection of C57BL/6J mice with mouse-adapted SARS-CoV results in high-titer virus replication within the lung, induction of inflammatory cytokines and chemokines, and immune cell infiltration within the lung. Using this model, we investigated the role of the complement system during SARS-CoV infection. We observed activation of the complement cascade in the lung as early as day 1 following SARS-CoV infection. To test whether this activation contributed to protective or pathologic outcomes, we utilized mice deficient in C3 (C3(–/–)), the central component of the complement system. Relative to C57BL/6J control mice, SARS-CoV-infected C3(–/–) mice exhibited significantly less weight loss and less respiratory dysfunction despite equivalent viral loads in the lung. Significantly fewer neutrophils and inflammatory monocytes were present in the lungs of C3(–/–) mice than in C56BL/6J controls, and subsequent studies revealed reduced lung pathology and lower cytokine and chemokine levels in both the lungs and the sera of C3(–/–) mice than in controls. These studies identify the complement system as an important host mediator of SARS-CoV-induced disease and suggest that complement activation regulates a systemic proinflammatory response to SARS-CoV infection. Furthermore, these data suggest that SARS-CoV-mediated disease is largely immune driven and that inhibiting complement signaling after SARS-CoV infection might function as an effective immune therapeutic.",2018 Oct 9,"['Gralinski, Lisa E.', 'Sheahan, Timothy P.', 'Morrison, Thomas E.', 'Menachery, Vineet D.', 'Jensen, Kara', 'Leist, Sarah R.', 'Whitmore, Alan', 'Heise, Mark T.', 'Baric, Ralph S.']",mBio,,,True
bc01fae970a5c27f2213ac75db374170444545f6,PMC,Monomeric Camelus dromedarius GSTM1 at low pH is structurally more thermostable than its native dimeric form,http://dx.doi.org/10.1371/journal.pone.0205274,PMC6179282,30303997,CC BY,"Glutathione S‒transferases (GSTs) are multifunctional enzymes that play an important role in detoxification, cellular signalling, and the stress response. Camelus dromedarius is well-adapted to survive in extreme desert climate and it has GSTs, for which limited information is available. This study investigated the structure-function and thermodynamic properties of a mu-class camel GST (CdGSTM1) at different pH. Recombinant CdGSTM1 (25.7 kDa) was expressed in E. coli and purified to homogeneity. Dimeric CdGSTM1 dissociated into stable but inactive monomeric subunits at low pH. Conformational and thermodynamic changes during the thermal unfolding pathway of dimeric and monomeric CdGSTM1 were characterised via a thermal shift assay and dynamic multimode spectroscopy (DMS). The thermal shift assay based on intrinsic tryptophan fluorescence revealed that CdGSTM1 underwent a two-state unfolding pathway at pH 1.0–10.0. Its Tm value varied with varying pH. Another orthogonal technique based on far-UV CD also exhibited two-state unfolding in the dimeric and monomeric states. Generally, proteins tend to lose structural integrity and stability at low pH; however, monomeric CdGSTM1 at pH 2.0 was thermally more stable and unfolded with lower van't Hoff enthalpy. The present findings provide essential information regarding the structural, functional, and thermodynamic properties of CdGSTM1 at pH 1.0–10.0.",2018 Oct 10,"['Malik, Ajamaluddin', 'Khan, Javed M.', 'Alamery, Salman F.', 'Fouad, Dalia', 'Labrou, Nikolaos E.', 'Daoud, Mohamed S.', 'Abdelkader, Mohamed O.', 'Ataya, Farid S.']",PLoS One,,,True
4ebae5a999522c721177ba353fbd95a72439e060,PMC,Nanoparticle Vaccines Against Infectious Diseases,http://dx.doi.org/10.3389/fimmu.2018.02224,PMC6180194,30337923,CC BY,"Due to emergence of new variants of pathogenic micro-organisms the treatment and immunization of infectious diseases have become a great challenge in the past few years. In the context of vaccine development remarkable efforts have been made to develop new vaccines and also to improve the efficacy of existing vaccines against specific diseases. To date, some vaccines are developed from protein subunits or killed pathogens, whilst several vaccines are based on live-attenuated organisms, which carry the risk of regaining their pathogenicity under certain immunocompromised conditions. To avoid this, the development of risk-free effective vaccines in conjunction with adequate delivery systems are considered as an imperative need to obtain desired humoral and cell-mediated immunity against infectious diseases. In the last several years, the use of nanoparticle-based vaccines has received a great attention to improve vaccine efficacy, immunization strategies, and targeted delivery to achieve desired immune responses at the cellular level. To improve vaccine efficacy, these nanocarriers should protect the antigens from premature proteolytic degradation, facilitate antigen uptake and processing by antigen presenting cells, control release, and should be safe for human use. Nanocarriers composed of lipids, proteins, metals or polymers have already been used to attain some of these attributes. In this context, several physico-chemical properties of nanoparticles play an important role in the determination of vaccine efficacy. This review article focuses on the applications of nanocarrier-based vaccine formulations and the strategies used for the functionalization of nanoparticles to accomplish efficient delivery of vaccines in order to induce desired host immunity against infectious diseases.",2018 Oct 4,"['Pati, Rashmirekha', 'Shevtsov, Maxim', 'Sonawane, Avinash']",Front Immunol,,,True
9bcf1d2a543d586018a6b55fd349a8c8b6b614a9,PMC,"Bordetella bronchiseptica Colonization Limits Efficacy, but Not Immunogenicity, of Live-Attenuated Influenza Virus Vaccine and Enhances Pathogenesis After Influenza Challenge",http://dx.doi.org/10.3389/fimmu.2018.02255,PMC6180198,30337924,CC BY,"Intranasally administered live-attenuated influenza virus (LAIV) vaccines provide significant protection against heterologous influenza A virus (IAV) challenge. However, LAIV administration can modify the bacterial microbiota in the upper respiratory tract, including alterations in species that cause pneumonia. We sought to evaluate the effect of Bordetella bronchiseptica colonization on LAIV immunogenicity and efficacy in swine, and the impact of LAIV and IAV challenge on B. bronchiseptica colonization and disease. LAIV immunogenicity was not significantly impacted by B. bronchiseptica colonization, but protective efficacy against heterologous IAV challenge in the upper respiratory tract was impaired. Titers of IAV in the nose and trachea of pigs that received LAIV were significantly reduced when compared to non-vaccinated, challenged controls, regardless of B. bronchiseptica infection. Pneumonia scores were higher in pigs colonized with B. bronchiseptica and challenged with IAV, but this was regardless of LAIV vaccination status. While LAIV vaccination provided significant protection against heterologous IAV challenge, the protection was not sterilizing and IAV replicated in the respiratory tract of all LAIV vaccinated pig. The interaction between IAV, B. bronchiseptica, and host led to development of acute-type B. bronchiseptica lesions in the lung. Thus, the data presented do not negate the efficacy of LAIV vaccination, but instead indicate that controlling B. bronchiseptica colonization in swine could limit the negative interaction between IAV and Bordetella on swine health.",2018 Oct 4,"['Hughes, Holly R.', 'Brockmeier, Susan L.', 'Loving, Crystal L.']",Front Immunol,,,True
b1d65769b15ff7bd395ae21186fd09642f69571f,PMC,"Zika Virus Infection at Different Pregnancy Stages: Anatomopathological Findings, Target Cells and Viral Persistence in Placental Tissues",http://dx.doi.org/10.3389/fmicb.2018.02266,PMC6180237,30337910,CC BY,"Zika virus (ZIKV) infection in humans has been associated with congenital malformations and other neurological disorders, such as Guillain-Barré syndrome. The mechanism(s) of ZIKV intrauterine transmission, the cell types involved, the most vulnerable period of pregnancy for severe outcomes from infection and other physiopathological aspects are not completely elucidated. In this study, we analyzed placental samples obtained at the time of delivery from a group of 24 women diagnosed with ZIKV infection during the first, second or third trimesters of pregnancy. Villous immaturity was the main histological finding in the placental tissues, although placentas without alterations were also frequently observed. Significant enhancement of the number of syncytial sprouts was observed in the placentas of women infected during the third trimester, indicating the development of placental abnormalities after ZIKV infection. Hyperplasia of Hofbauer cells (HCs) was also observed in these third-trimester placental tissues, and remarkably, HCs were the only ZIKV-positive fetal cells found in the placentas studied that persisted until birth, as revealed by immunohistochemical (IHC) analysis. Thirty-three percent of women infected during pregnancy delivered infants with congenital abnormalities, although no pattern correlating the gestational stage at infection, the IHC positivity of HCs in placental tissues and the presence of congenital malformations at birth was observed. Placental tissue analysis enabled us to confirm maternal ZIKV infection in cases where serum from the acute infection phase was not available, which reinforces the importance of this technique in identifying possible causal factors of birth defects. The results we observed in the samples from naturally infected pregnant women may contribute to the understanding of some aspects of the pathophysiology of ZIKV.",2018 Sep 25,"['de Noronha, Lucia', 'Zanluca, Camila', 'Burger, Marion', 'Suzukawa, Andreia Akemi', 'Azevedo, Marina', 'Rebutini, Patricia Z.', 'Novadzki, Iolanda Maria', 'Tanabe, Laurina Setsuko', 'Presibella, Mayra Marinho', 'Duarte dos Santos, Claudia Nunes']",Front Microbiol,,,True
360d7a85fefdad638d52a705f668d2047fc63ce7,PMC,"Characterization of patients transported with extracorporeal respiratory and/or cardiovascular support in the State of São Paulo, Brazil",http://dx.doi.org/10.5935/0103-507X.20180052,PMC6180471,30328986,CC BY,"OBJECTIVE: To characterize the transport of severely ill patients with extracorporeal respiratory or cardiovascular support. METHODS: A series of 18 patients in the state of São Paulo, Brazil is described. All patients were consecutively evaluated by a multidisciplinary team at the hospital of origin. The patients were rescued, and extracorporeal membrane oxygenation support was provided on site. The patients were then transported to referral hospitals for extracorporeal membrane oxygenation support. Data were retrieved from a prospectively collected database. RESULTS: From 2011 to 2017, 18 patients aged 29 (25 - 31) years with a SAPS 3 of 84 (68 - 92) and main primary diagnosis of leptospirosis and influenza A (H1N1) virus were transported to three referral hospitals in São Paulo. A median distance of 39 (15 - 82) km was traveled on each rescue mission during a period of 360 (308 - 431) min. A median of one (0 - 2) nurse, three (2 - 3) physicians, and one (0 - 1) physical therapist was present per rescue. Seventeen rescues were made by ambulance, and one rescue was made by helicopter. The observed complications were interruption in the energy supply to the pump in two cases (11%) and oxygen saturation < 70% in two cases. Thirteen patients (72%) survived and were discharged from the hospital. Among the nonsurvivors, there were two cases of brain death, two cases of multiple organ dysfunction syndrome, and one case of irreversible pulmonary fibrosis. CONCLUSIONS: Transportation with extracorporeal support occurred without serious complications, and the hospital survival rate was high.",2018,"['Li, Ho Yeh', 'Mendes, Pedro Vitale', 'Melro, Livia Maria Garcia', 'Joelsons, Daniel', 'Besen, Bruno Adler Maccagnan Pinheiro', 'Costa, Eduardo Leite Viera', 'Hirota, Adriana Sayuri', 'Barbosa, Edzangela Vasconcelos Santos', 'Foronda, Flavia Krepel', 'Azevedo, Luciano Cesar Pontes', 'Romano, Thiago Gomes', 'Park, Marcelo']",Rev Bras Ter Intensiva,,,True
97d0e0033e74b01cefd3c71a23aa1fec45a72296,PMC,"Characterization of patients transported with extracorporeal respiratory and/or cardiovascular support in the State of São Paulo, Brazil",http://dx.doi.org/10.5935/0103-507X.20180052,PMC6180471,30328986,CC BY,"OBJECTIVE: To characterize the transport of severely ill patients with extracorporeal respiratory or cardiovascular support. METHODS: A series of 18 patients in the state of São Paulo, Brazil is described. All patients were consecutively evaluated by a multidisciplinary team at the hospital of origin. The patients were rescued, and extracorporeal membrane oxygenation support was provided on site. The patients were then transported to referral hospitals for extracorporeal membrane oxygenation support. Data were retrieved from a prospectively collected database. RESULTS: From 2011 to 2017, 18 patients aged 29 (25 - 31) years with a SAPS 3 of 84 (68 - 92) and main primary diagnosis of leptospirosis and influenza A (H1N1) virus were transported to three referral hospitals in São Paulo. A median distance of 39 (15 - 82) km was traveled on each rescue mission during a period of 360 (308 - 431) min. A median of one (0 - 2) nurse, three (2 - 3) physicians, and one (0 - 1) physical therapist was present per rescue. Seventeen rescues were made by ambulance, and one rescue was made by helicopter. The observed complications were interruption in the energy supply to the pump in two cases (11%) and oxygen saturation < 70% in two cases. Thirteen patients (72%) survived and were discharged from the hospital. Among the nonsurvivors, there were two cases of brain death, two cases of multiple organ dysfunction syndrome, and one case of irreversible pulmonary fibrosis. CONCLUSIONS: Transportation with extracorporeal support occurred without serious complications, and the hospital survival rate was high.",2018,"['Li, Ho Yeh', 'Mendes, Pedro Vitale', 'Melro, Livia Maria Garcia', 'Joelsons, Daniel', 'Besen, Bruno Adler Maccagnan Pinheiro', 'Costa, Eduardo Leite Viera', 'Hirota, Adriana Sayuri', 'Barbosa, Edzangela Vasconcelos Santos', 'Foronda, Flavia Krepel', 'Azevedo, Luciano Cesar Pontes', 'Romano, Thiago Gomes', 'Park, Marcelo']",Rev Bras Ter Intensiva,,,True
a8d63649b68d0dc86f49b474ef863ece99f915a2,PMC,Rapid detection of respiratory organisms with the FilmArray respiratory panel in a large children’s hospital in China,http://dx.doi.org/10.1186/s12879-018-3429-6,PMC6180626,30305033,CC BY,"BACKGROUND: Respiratory tract infections (RTIs) are the most common illness in children, and rapid diagnosis is required for the optimal management of RTIs, especially severe infections. METHODS: Nasopharyngeal swab or sputum specimens were collected from children aged 19 days to 15 years who were admitted to a hospital in Shanghai and diagnosed with RTIs. The specimens were tested with the FilmArray Respiratory Panel, a multiplex PCR assay that detects 16 viruses, Mycoplasma pneumoniae (M. pneumoniae), Bordetella pertussis (B. pertussis) and Chlamydophila pneumoniae (C. pneumoniae). RESULTS: Among the 775 children studied, 626 (80.8%, 626/775) tested positive for at least one organism, and multiple organisms were detected in 198 (25.5%). Rhinoviruses/enteroviruses (25.5%, 198/775) were detected most often, followed by respiratory syncytial virus (19.5%, 151/775), parainfluenza virus 3 (14.8%, 115/775), influenza A or B (10.9%), adenovirus (10.8%), M. pneumoniae (10.6%) and B. pertussis (6.3%). The prevalence of organisms differed by age, and most of the viruses were more common in winter. Of the 140 children suspected of having pertussis, 35.0% (49/140) tested positive for B. pertussis. CONCLUSIONS: FilmArray RP allows the rapid simultaneous detection of a wide number of respiratory organisms, with limited hands-on time, in Chinese pediatric patients with RTIs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3429-6) contains supplementary material, which is available to authorized users.",2018 Oct 11,"['Li, Jin', 'Tao, Yue', 'Tang, Mingyu', 'Du, Bailu', 'Xia, Yijun', 'Mo, Xi', 'Cao, Qing']",BMC Infect Dis,,,True
6440df901a6f813d155848ba6f130c75e34d7f7b,PMC,Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission,http://dx.doi.org/10.1038/s41598-018-33487-8,PMC6181990,30310104,CC BY,"A 29 nucleotide deletion in open reading frame 8 (ORF8) is the most obvious genetic change in severe acute respiratory syndrome coronavirus (SARS-CoV) during its emergence in humans. In spite of intense study, it remains unclear whether the deletion actually reflects adaptation to humans. Here we engineered full, partially deleted (−29 nt), and fully deleted ORF8 into a SARS-CoV infectious cDNA clone, strain Frankfurt-1. Replication of the resulting viruses was compared in primate cell cultures as well as Rhinolophus bat cells made permissive for SARS-CoV replication by lentiviral transduction of the human angiotensin-converting enzyme 2 receptor. Cells from cotton rat, goat, and sheep provided control scenarios that represent host systems in which SARS-CoV is neither endemic nor epidemic. Independent of the cell system, the truncation of ORF8 (29 nt deletion) decreased replication up to 23-fold. The effect was independent of the type I interferon response. The 29 nt deletion in SARS-CoV is a deleterious mutation acquired along the initial human-to-human transmission chain. The resulting loss of fitness may be due to a founder effect, which has rarely been documented in processes of viral emergence. These results have important implications for the retrospective assessment of the threat posed by SARS.",2018 Oct 11,"['Muth, Doreen', 'Corman, Victor Max', 'Roth, Hanna', 'Binger, Tabea', 'Dijkman, Ronald', 'Gottula, Lina Theresa', 'Gloza-Rausch, Florian', 'Balboni, Andrea', 'Battilani, Mara', 'Rihtarič, Danijela', 'Toplak, Ivan', 'Ameneiros, Ramón Seage', 'Pfeifer, Alexander', 'Thiel, Volker', 'Drexler, Jan Felix', 'Müller, Marcel Alexander', 'Drosten, Christian']",Sci Rep,,,False
49e262acc674f6765222a7b46b8eb1c78aeda947,PMC,Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission,http://dx.doi.org/10.1038/s41598-018-33487-8,PMC6181990,30310104,CC BY,"A 29 nucleotide deletion in open reading frame 8 (ORF8) is the most obvious genetic change in severe acute respiratory syndrome coronavirus (SARS-CoV) during its emergence in humans. In spite of intense study, it remains unclear whether the deletion actually reflects adaptation to humans. Here we engineered full, partially deleted (−29 nt), and fully deleted ORF8 into a SARS-CoV infectious cDNA clone, strain Frankfurt-1. Replication of the resulting viruses was compared in primate cell cultures as well as Rhinolophus bat cells made permissive for SARS-CoV replication by lentiviral transduction of the human angiotensin-converting enzyme 2 receptor. Cells from cotton rat, goat, and sheep provided control scenarios that represent host systems in which SARS-CoV is neither endemic nor epidemic. Independent of the cell system, the truncation of ORF8 (29 nt deletion) decreased replication up to 23-fold. The effect was independent of the type I interferon response. The 29 nt deletion in SARS-CoV is a deleterious mutation acquired along the initial human-to-human transmission chain. The resulting loss of fitness may be due to a founder effect, which has rarely been documented in processes of viral emergence. These results have important implications for the retrospective assessment of the threat posed by SARS.",2018 Oct 11,"['Muth, Doreen', 'Corman, Victor Max', 'Roth, Hanna', 'Binger, Tabea', 'Dijkman, Ronald', 'Gottula, Lina Theresa', 'Gloza-Rausch, Florian', 'Balboni, Andrea', 'Battilani, Mara', 'Rihtarič, Danijela', 'Toplak, Ivan', 'Ameneiros, Ramón Seage', 'Pfeifer, Alexander', 'Thiel, Volker', 'Drexler, Jan Felix', 'Müller, Marcel Alexander', 'Drosten, Christian']",Sci Rep,,,True
f5fd6b1f388f2244e5631dacb82c774638d30797,PMC,Intermediate compartment (IC): from pre-Golgi vacuoles to a semi-autonomous membrane system,http://dx.doi.org/10.1007/s00418-018-1717-2,PMC6182704,30173361,CC BY,"Despite its discovery more than three decades ago and well-established role in protein sorting and trafficking in the early secretory pathway, the intermediate compartment (IC) has remained enigmatic. The prevailing view is that the IC evolved as a specialized organelle to mediate long-distance endoplasmic reticulum (ER)–Golgi communication in metazoan cells, but is lacking in other eukaryotes, such as plants and fungi. However, this distinction is difficult to reconcile with the high conservation of the core machineries that regulate early secretory trafficking from yeast to man. Also, it has remained unclear whether the pleiomorphic IC components—vacuoles, tubules and vesicles—represent transient transport carriers or building blocks of a permanent pre-Golgi organelle. Interestingly, recent studies have revealed that the IC maintains its compositional, structural and spatial properties throughout the cell cycle, supporting a model that combines the dynamic and stable aspects of the organelle. Moreover, the IC has been assigned novel functions, such as cell signaling, Golgi-independent trafficking and autophagy. The emerging permanent nature of the IC and its connections with the centrosome and the endocytic recycling system encourage reconsideration of its relationship with the Golgi ribbon, role in Golgi biogenesis and ubiquitous presence in eukaryotic cells.",2018 Sep 1,"['Saraste, Jaakko', 'Marie, Michaël']",Histochem Cell Biol,,,True
e0668c4b793d0cad26639b070819334a94648123,PMC,‘Hajj: what it means for general practice’,http://dx.doi.org/10.3399/bjgpopen18X101493,PMC6184103,30564715,CC BY,,2018 Apr 18,"['Mughal, Faraz', 'Chew-Graham, Carolyn A', 'Saad, Ahmad']",BJGP Open,,,True
7ef029ee55ef6b0a0e6443f8ca750e0569024789,PMC,Construction of a recombinant rhinovirus accommodating fluorescent marker expression,http://dx.doi.org/10.1111/irv.12602,PMC6185886,30120824,CC BY,"BACKGROUND: Rhinovirus (RV) causes the common cold and asthma exacerbations. The RV genome is a 7.3 kb single‐strand positive‐sense RNA. OBJECTIVE: Using minor group RV1A as a backbone, we sought to design and generate a recombinant RV1A accommodating fluorescent marker expression, thereby allowing tracking of viral infection. METHOD: Recombinant RV1A infectious cDNA clones harboring the coding sequence of green fluorescent protein (GFP), Renilla luciferase, or iLOV (for light, oxygen, or voltage sensing) were engineered and constructed. RV‐infected cells were determined by flow cytometry, immunohistochemistry, and immunofluorescence microscopy. RESULTS: RV1A‐GFP showed a cytopathic effect in HeLa cells but failed to express GFP or Renilla luciferase due to deletion. The smaller fluorescent protein construct, RV1A‐iLOV, was stably expressed in infected cells. RV1A‐iLOV expression was used to examine the antiviral effect of bafilomycin in HeLa cells. Compared to parental virus, RV1A‐iLOV infection of BALB/c mice yielded a similar viral load and level of cytokine mRNA expression. However, imaging of fixed lung tissue failed to reveal a fluorescent signal, likely due to the oxidation and bleaching of iLOV‐bound flavin mononucleotide. We therefore employed an anti‐iLOV antibody for immunohistochemical and immunofluorescence imaging. The iLOV signal was identified in airway epithelial cells and CD45+ CD11b+ lung macrophages. CONCLUSIONS: These results suggest that RV1A‐iLOV is a useful molecular tool for studying RV pathogenesis. The construction strategy for RV1A‐iLOV could be applied to other RV serotypes. However, the detection of iLOV‐expressing RV in fixed tissue required the use of an anti‐iLOV antibody, limiting the value of this construct.",2018 Nov 6,"['Han, Mingyuan', 'Rajput, Charu', 'Hinde, Joanna L.', 'Wu, Qian', 'Lei, Jing', 'Ishikawa, Tomoko', 'Bentley, J. Kelley', 'Hershenson, Marc B.']",Influenza Other Respir Viruses,,,True
57da78ec8de4f8fd1761c46221d0e05872f14f1f,PMC,Risk factors for bronchiolitis severity: A retrospective review of patients admitted to the university hospital from central region of Slovenia,http://dx.doi.org/10.1111/irv.12587,PMC6185887,29944781,CC BY,"AIM: Study's objective was to identify risk factors associated with bronchiolitis severity. METHODS: A retrospective chart review of all children <2 years old diagnosed with bronchiolitis at the University Medical Centre Ljubljana between May 2014 and April 2015, who were treated as outpatients (paediatric emergency department, PED group) or as inpatients in the standard hospital setting (WARD group) or in the paediatric intensive care unit (PICU group). Detection of respiratory viruses in nasopharyngeal swab was accomplished by RT‐PCR. Severity was assessed by Wang Respiratory Score and hospitalization longer than 24 hours. RESULTS: The study included 761 children. The three most frequently detected viruses were respiratory syncytial virus (RSV), human rhinovirus (hRV) and human bocavirus (hBoV) (57.5%, 272/473; 25.6%, 121/473; 18.4%, 87/473). Patient groups differed in Wang Respiratory Score for the severity of bronchiolitis (P < 0.001). No differences regarding the causative viruses were found. There was a lower proportion of children with the presence of more than one virus in PICU group compared to other two groups (P = 0.017). The three groups significantly differed in age, birthweight, comorbidities, bronchodilator treatment and antibiotic usage. However, multiple regression analysis revealed that younger age and the use of antibiotics were associated with bronchiolitis severity defined as hospitalization for >24 hours. CONCLUSIONS: Respiratory syncytial virus, hRV and hBoV were the most frequently detected viruses. The majority of patients admitted to the PICU had only one virus detected. Younger age and the use of antibiotics were associated with bronchiolitis severity.",2018 Nov 9,"['Praznik, Ajda', 'Vinšek, Neža', 'Prodan, Ana', 'Erčulj, Vanja', 'Pokorn, Marko', 'Mrvič, Tatjana', 'Paro, Darja', 'Krivec, Uroš', 'Strle, Franc', 'Petrovec, Miroslav', 'Žnidaršič Eržen, Marta', 'Grosek, Štefan']",Influenza Other Respir Viruses,,,True
b1d8740e2366dfb7237e416b257905c5bb06f349,PMC,Seasonality and clinical impact of human parainfluenza viruses,http://dx.doi.org/10.1111/irv.12597,PMC6185891,30051619,CC BY,"BACKGROUND: Widespread availability of rapid diagnostic testing for respiratory viruses allows more in‐depth studies of human parainfluenza viruses (HPIV). OBJECTIVES: This study aimed to assess seasonality of HPIV types 1‐4, clinical outcomes by HPIV type, and risk factors for illness severity. PATIENTS/METHODS: This retrospective study was performed from January 2013 to December 2015 in children and adults with HPIV, detected by multiplex reverse transcription polymerase chain reaction, participating in a community surveillance study of acute respiratory infections (ARIs) in New York City and patients admitted to a tertiary care center in the same neighborhood. Seasonality trends by HPIV type were compared between the community and hospital groups. The associations between HPIV type, demographics, clinical characteristics, and illness severity were assessed. RESULTS: HPIV was detected in 69 (4%) of 1753 community surveillance participants (median age 9.2 years) and 680 hospitalized patients (median age 6.8 years). Seasonality for HPIV types 1‐3 agreed with previously described patterns; HPIV‐4 occurred annually in late summer and fall. In the community cohort, 22 (32%) participants sought medical care, 9 (13%) reported antibiotic use, and 20 (29%) reported ≥1 day of missed work or school. Among hospitalized patients, 24% had ≥4 chronic conditions. Multivariable ordinal logistic regression demonstrated that increased severity of illness was significantly associated with HPIV‐4 and chronic cardiovascular and respiratory conditions in children and with age ≥65 years and chronic respiratory conditions in adults. CONCLUSIONS: HPIV‐4 presented late summer and early fall annually and was associated with increased severity of illness in hospitalized children.",2018 Nov 29,"['Maykowski, Philip', 'Smithgall, Marie', 'Zachariah, Philip', 'Oberhardt, Matthew', 'Vargas, Celibell', 'Reed, Carrie', 'Demmer, Ryan T.', 'Stockwell, Melissa S.', 'Saiman, Lisa']",Influenza Other Respir Viruses,,,True
71df4de7c682eada32158ed24cba1b028a661c87,PMC,Establishment of porcine enterocyte/myofibroblast co-cultures for the growth of porcine rota- and coronaviruses,http://dx.doi.org/10.1038/s41598-018-33305-1,PMC6185943,30315177,CC BY,"A stable culture of primary porcine enterocytes is necessary to study porcine enteric virus replication characteristics. Because the direct cultivation of primary porcine enterocytes is difficult, alternatives have to be considered. As subepithelial myofibroblasts secrete extracellular matrix and growth factors contributing to the attachment, proliferation and differentiation of epithelial cells, co-cultures of primary porcine enterocytes (ileocytes and colonocytes) with myofibroblasts were developed and evaluated for their susceptibility to enteric viruses. First, it was demonstrated that the co-cultured ileocytes and colonocytes were susceptible to an archival rotavirus strain RVA/pig-tc/BEL/RV277/1977/G1P[7] and different other rotavirus genotypes (fecal samples containing G5P[7], G5P[13], G9P[23], G4P[6]). Next, the TGEV Purdue strain infected both ileocytes and colonocytes whereas the Miller strain only infected ileocytes. Last, the PEDV CV777 Vero adapted and non-adapted (fecal suspension) strains could infect co-cultured ileocytes but not colonocytes. The infectivity of the CV777 Vero adapted strain was higher when the cells were cultured without fetal bovine serum and the CV777 fecal suspension only infected the ileocytes cultured without fetal bovine serum. In conclusion, a novel co-culture of porcine enterocytes with myofibroblasts was established, which can be used for the investigation of the replication of enteric viruses.",2018 Oct 12,"['Cui, Tingting', 'Theuns, Sebastiaan', 'Desmarets, Lowiese M. B.', 'Xie, Jiexiong', 'De Gryse, Gaëtan M. A.', 'Yang, Bo', 'Van den Broeck, Wim', 'Nauwynck, Hans J.']",Sci Rep,,,False
436e61a48e3f8612480cb7261040897dfa875524,PMC,Establishment of porcine enterocyte/myofibroblast co-cultures for the growth of porcine rota- and coronaviruses,http://dx.doi.org/10.1038/s41598-018-33305-1,PMC6185943,30315177,CC BY,"A stable culture of primary porcine enterocytes is necessary to study porcine enteric virus replication characteristics. Because the direct cultivation of primary porcine enterocytes is difficult, alternatives have to be considered. As subepithelial myofibroblasts secrete extracellular matrix and growth factors contributing to the attachment, proliferation and differentiation of epithelial cells, co-cultures of primary porcine enterocytes (ileocytes and colonocytes) with myofibroblasts were developed and evaluated for their susceptibility to enteric viruses. First, it was demonstrated that the co-cultured ileocytes and colonocytes were susceptible to an archival rotavirus strain RVA/pig-tc/BEL/RV277/1977/G1P[7] and different other rotavirus genotypes (fecal samples containing G5P[7], G5P[13], G9P[23], G4P[6]). Next, the TGEV Purdue strain infected both ileocytes and colonocytes whereas the Miller strain only infected ileocytes. Last, the PEDV CV777 Vero adapted and non-adapted (fecal suspension) strains could infect co-cultured ileocytes but not colonocytes. The infectivity of the CV777 Vero adapted strain was higher when the cells were cultured without fetal bovine serum and the CV777 fecal suspension only infected the ileocytes cultured without fetal bovine serum. In conclusion, a novel co-culture of porcine enterocytes with myofibroblasts was established, which can be used for the investigation of the replication of enteric viruses.",2018 Oct 12,"['Cui, Tingting', 'Theuns, Sebastiaan', 'Desmarets, Lowiese M. B.', 'Xie, Jiexiong', 'De Gryse, Gaëtan M. A.', 'Yang, Bo', 'Van den Broeck, Wim', 'Nauwynck, Hans J.']",Sci Rep,,,True
3bc70642b00cb1e53c8a6c83a584e429d626d199,PMC,Differentially expressed non-coding RNAs induced by transmissible gastroenteritis virus potentially regulate inflammation and NF-κB pathway in porcine intestinal epithelial cell line,http://dx.doi.org/10.1186/s12864-018-5128-5,PMC6186045,30314467,CC BY,"BACKGROUND: Transmissible gastroenteritis virus (TGEV) infection can activate NF-κB pathway in porcine intestinal epithelial cells and result in severe inflammation. Non-coding RNAs (ncRNAs) are not translated into proteins and play an important role in many biological and pathological processes such as inflammation, viral infection, and mitochondrial damage. However, whether ncRNAs participate in TGEV-induced inflammation in porcine intestinal epithelial cells is largely unknown. RESULTS: In this study, the next-generation sequencing (NGS) technology was used to analyze the profiles of mRNAs, miRNAs, and circRNAs in Mock- and TGEV-infected intestinal porcine epithelial cell-jejunum 2 (IPEC-J2) cell line. A total of 523 mRNAs, 65 microRNAs (miRNAs), and 123 circular RNAs (circRNAs) were differentially expressed. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed differentially expressed mRNAs were linked to inflammation-related pathways, including NF-κB, Toll-like receptor, NOD-like receptor, Jak-STAT, TNF, and RIG-I-like receptor pathways. The interactions among mRNA, miRNA, and circRNA were analyzed. The data showed that ssc_circ_009380 and miR-22 might have interaction relationship. Dual-luciferase reporter assay confirmed that miR-22 directly bound to ssc_circ_009380. We also observed that overexpression of miR-22 led to a reduction of p-IκB-α and accumulation of p65 in nucleus in TGEV-infected IPEC-J2 cells. In contrast, inhibition of miR-22 had the opposite effects. Moreover, silencing of ssc_circ_009380 inhibited accumulation of p65 in nucleus and phosphorylation of IκB-α. CONCLUSIONS: The data revealed that differentially expressed mRNAs and ncRNAs were primarily enriched in inflammation-related pathways and ssc_circ_009380 promoted activation of NF-κB pathway by binding miR-22 during TGEV-induced inflammation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-5128-5) contains supplementary material, which is available to authorized users.",2018 Oct 12,"['Ma, Xuelian', 'Zhao, Xiaomin', 'Zhang, Zhichao', 'Guo, Jianxiong', 'Guan, Lijuan', 'Li, Juejun', 'Mi, Mi', 'Huang, Yong', 'Tong, Dewen']",BMC Genomics,,,True
3aae9e36468d7e3e26825d23997b612d7ce755b7,PMC,CD9 Tetraspanin: A New Pathway for the Regulation of Inflammation?,http://dx.doi.org/10.3389/fimmu.2018.02316,PMC6189363,30356731,CC BY,"CD9 belongs to the tetraspanin superfamily. Depending on the cell type and associated molecules, CD9 has a wide variety of biological activities such as cell adhesion, motility, metastasis, growth, signal transduction, differentiation, and sperm–egg fusion. This review focuses on CD9 expression by hematopoietic cells and its role in modulating cellular processes involved in the regulation of inflammation. CD9 is functionally very important in many diseases and is involved either in the regulation or in the mediation of the disease. The role of CD9 in various diseases, such as viral and bacterial infections, cancer and chronic lung allograft dysfunction, is discussed. This review focuses also on its interest as a biomarker in diseases. Indeed CD9 is primarily known as a specific exosome marker however, its expression is now recognized as an anti-inflammatory marker of monocytes and macrophages. It was also described as a marker of murine IL-10-competent Breg cells and IL-10-secreting CD9(+) B cells were associated with better allograft outcome in lung transplant patients, and identified as a new predictive biomarker of long-term survival. In the field of cancer, CD9 was both identified as a favorable prognostic marker or as a predictor of metastatic potential depending on cancer types. Finally, this review discusses strategies to target CD9 as a therapeutic tool. Because CD9 can have opposite effects depending on the situation, the environment and the pathology, modulating CD9 expression or blocking its effects seem to be a new promising therapeutic strategy.",2018 Oct 9,"['Brosseau, Carole', 'Colas, Luc', 'Magnan, Antoine', 'Brouard, Sophie']",Front Immunol,,,True
6003e4441a559c056ce473a86dca5db1e2a9bf8d,PMC,Mass spectrometry-based identification and whole-genome characterisation of the first pteropine orthoreovirus isolated from monkey faeces in Thailand,http://dx.doi.org/10.1186/s12866-018-1302-9,PMC6192116,30332986,CC BY,"BACKGROUND: The pteropine orthoreovirus (PRV) was isolated from monkey (Macaca fascicularis) faecal samples collected from human-inhabited areas in Lopburi Province, Thailand. These samples were initially obtained to survey for the presence of hepatitis E virus (HEV). RESULTS: Two virus isolates were retrieved by virus culture of 55 monkey faecal samples. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was successfully used to identify the viruses as the segmented dsRNA orthoreovirus. Phylogenetic analysis of the Lopburi orthoreovirus whole-genomes revealed relationships with the well-characterised PRVs Pulau (segment L1), Cangyuan (segments L2, M3 and S3), Melaka (segments L3 and M2), Kampar (segments M1 and S2) and Sikamat (segments S1 and S4) of Southeast Asia and China with nucleotide sequence identities of 93.5–98.9%. RT-PCR showed that PRV was detected in 10.9% (6/55) and HEV was detected in 25.5% (14/55) of the monkey faecal samples. CONCLUSIONS: PRV was isolated from monkey faeces for the first time in Thailand via viral culture and LC-MS/MS. The genetic diversity of the virus genome segments suggested a re-assortment within the PRV species group. The overall findings emphasise that monkey faeces can be sources of zoonotic viruses, including PRV and HEV, and suggest the need for active virus surveillance in areas of human and monkey co-habitation to prevent and control emerging zoonotic diseases in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12866-018-1302-9) contains supplementary material, which is available to authorized users.",2018 Oct 17,"['Kosoltanapiwat, Nathamon', 'Reamtong, Onrapak', 'Okabayashi, Tamaki', 'Ampawong, Sumate', 'Rungruengkitkun, Amporn', 'Thiangtrongjit, Tipparat', 'Thippornchai, Narin', 'Leaungwutiwong, Pornsawan', 'Mahittikorn, Aongart', 'Mori, Hirotake', 'Yoohanngoa, Thanada', 'Yamwong, Prechaya']",BMC Microbiol,,,True
e0af0e80af8fd724d1a23f90590617d72b452e1b,PMC,Profile of resistance to IVIG treatment in patients with Kawasaki disease and concomitant infection,http://dx.doi.org/10.1371/journal.pone.0206001,PMC6192641,30332473,CC BY,"INTRODUCTION: Kawasaki disease (KD) can be associated with concomitant viral or bacterial infections. Children with persistent or recurrent fever 36 hours after the end of intravenous immunoglobulin (IVIG) are considered to be resistant to treatment and are at increased risk for coronary complications. Although concomitant infection does not affect coronary outcome, it is unknown how it influences the response to IVIG treatment. METHODOLOGY: Retrospective cohort study between 2008 and 2016 in a tertiary pediatric university hospital, including 154 children, of which 59 (38%) had concomitant infection. RESULTS: Children with concomitant infection were more likely to have fever 48 hours after initial IVIG treatment (36% vs 20%, p = 0.05) and to be treated with a second dose (33% vs 18%, p = 0.04). Children with infection had higher C-reactive protein at the time of diagnosis (148 vs 112 mg/L, p = 0.04), and 48 hours after IVIG administration (111 vs 59 mg/L, p = 0.003). Nevertheless, there was no statistically significant difference in the prevalence of coronary complications (Z-score > 2.5) between children with and without concomitant infection (36% vs 39%, p = 0.68). CONCLUSION: Children with KD and concomitant infection are more likely to have persistent fever and elevated inflammatory markers after treatment. This association increases the likelihood of receiving a second dose of IVIG but not the risk of coronary complication. Accordingly, prospective studies to distinguish true IVIG resistance from infection induced persistent fever is warranted.",2018 Oct 17,"['Dionne, Audrey', 'Le, Cathie-Kim', 'Poupart, Steffany', 'Autmizguine, Julie', 'Meloche-Dumas, Léamarie', 'Turgeon, Jean', 'Fournier, Anne', 'Dahdah, Nagib']",PLoS One,,,True
83338ce69242b1a646ff6cd0234ae9d4197c374a,PMC,Review of global sanitation development,http://dx.doi.org/10.1016/j.envint.2018.07.047,PMC6192828,30103124,CC BY,"The implementation of the United Nations (UN) Millennium Development Goals (MDGs) and Sustainable Development Goals (SDGs) has resulted in an increased focus on developing innovative, sustainable sanitation techniques to address the demand for adequate and equitable sanitation in low-income areas. We examined the background, current situation, challenges, and perspectives of global sanitation. We used bibliometric analysis and word cluster analysis to evaluate sanitation research from 1992 to 2016 based on the Science Citation Index EXPANDED (SCI-EXPANDED) and Social Sciences Citation Index (SSCI) databases. Our results show that sanitation is a comprehensive field connected with multiple categories, and the increasing number of publications reflects a strong interest in this research area. Most of the research took place in developed countries, especially the USA, although sanitation problems are more serious in developing countries. Innovations in sanitation techniques may keep susceptible populations from contracting diseases caused by various kinds of contaminants and microorganisms. Hence, the hygienization of human excreta, resource recovery, and removal of micro-pollutants from excreta can serve as effective sustainable solutions. Commercialized technologies, like composting, anaerobic digestion, and storage, are reliable but still face challenges in addressing the links between the political, social, institutional, cultural, and educational aspects of sanitation. Innovative technologies, such as Microbial Fuel Cells (MFCs), Microbial Electrolysis Cells (MECs), and struvite precipitation, are at the TRL (Technology readiness levels) 8 level, meaning that they qualify as “actual systems completed and qualified through test and demonstration.” Solutions that take into consideration economic feasibility and all the different aspects of sanitation are required. There is an urgent demand for holistic solutions considering government support, social acceptability, as well as technological reliability that can be effectively adapted to local conditions.",2018 Nov,"['Zhou, Xiaoqin', 'Li, Zifu', 'Zheng, Tianlong', 'Yan, Yichang', 'Li, Pengyu', 'Odey, Emmanuel Alepu', 'Mang, Heinz Peter', 'Uddin, Sayed Mohammad Nazim']",Environ Int,,,False
aa80dd33eb3cc7ebcabeaee4b46635b8ddb64f4c,PMC,Investigation of the viral and bacterial microbiota in intestinal samples from mink (Neovison vison) with pre-weaning diarrhea syndrome using next generation sequencing,http://dx.doi.org/10.1371/journal.pone.0205890,PMC6193705,30335814,CC BY,"Pre-weaning diarrhea (PWD) in mink kits is a common multifactorial syndrome on commercial mink farms. Several potential pathogens such as astroviruses, caliciviruses, Escherichia coli and Staphylococcus delphini have been studied, but the etiology of the syndrome seems complex. In pooled samples from 38 diarrheic and 42 non-diarrheic litters, each comprising of intestinal contents from 2–3 mink kits from the same litter, the bacterial populations were studied using Illumina Next Generation Sequencing technology and targeted 16S amplicon sequencing. In addition, we used deep sequencing to determine and compare the viral intestinal content in 31 healthy non-diarrheic and 30 diarrheic pooled samples (2–3 mink kits from the same litter per pool). The results showed high variations in composition of the bacterial species between the pools. Enterococci, staphylococci and streptococci dominated in both diarrheic and non-diarrheic pools. However, enterococci accounted for 70% of the reads in the diarrheic group compared to 50% in the non-diarrheic group and this increase was at the expense of staphylococci and streptococci which together accounted for 45% and 17% of the reads in the non-diarrheic and diarrheic group, respectively. Moreover, in the diarrheic pools there were more reads assigned to Clostridia, Escherichia-Shigella and Enterobacter compared to the non-diarrheic pools. The taxonomically categorized sequences from the virome showed that the most prevalent viruses in all pools were caliciviruses and mamastroviruses (almost exclusively type 10). However, the numbers of reads assigned to caliciviruses were almost 3 times higher in the diarrheic pools compared the non-diarrheic pools and Sapporo-like caliciviruses were more abundant than the Norwalk-like caliciviruses. The results from this study have contributed to the insight into the changes in the intestinal microbiota associated with the PWD syndrome of mink.",2018 Oct 18,"['Birch, Julie Melsted', 'Ullman, Karin', 'Struve, Tina', 'Agger, Jens Frederik', 'Hammer, Anne Sofie', 'Leijon, Mikael', 'Jensen, Henrik Elvang']",PLoS One,,,True
0949cbed82da649dfcca3871e28d5a196720044b,PMC,Investigation of the viral and bacterial microbiota in intestinal samples from mink (Neovison vison) with pre-weaning diarrhea syndrome using next generation sequencing,http://dx.doi.org/10.1371/journal.pone.0205890,PMC6193705,30335814,CC BY,"Pre-weaning diarrhea (PWD) in mink kits is a common multifactorial syndrome on commercial mink farms. Several potential pathogens such as astroviruses, caliciviruses, Escherichia coli and Staphylococcus delphini have been studied, but the etiology of the syndrome seems complex. In pooled samples from 38 diarrheic and 42 non-diarrheic litters, each comprising of intestinal contents from 2–3 mink kits from the same litter, the bacterial populations were studied using Illumina Next Generation Sequencing technology and targeted 16S amplicon sequencing. In addition, we used deep sequencing to determine and compare the viral intestinal content in 31 healthy non-diarrheic and 30 diarrheic pooled samples (2–3 mink kits from the same litter per pool). The results showed high variations in composition of the bacterial species between the pools. Enterococci, staphylococci and streptococci dominated in both diarrheic and non-diarrheic pools. However, enterococci accounted for 70% of the reads in the diarrheic group compared to 50% in the non-diarrheic group and this increase was at the expense of staphylococci and streptococci which together accounted for 45% and 17% of the reads in the non-diarrheic and diarrheic group, respectively. Moreover, in the diarrheic pools there were more reads assigned to Clostridia, Escherichia-Shigella and Enterobacter compared to the non-diarrheic pools. The taxonomically categorized sequences from the virome showed that the most prevalent viruses in all pools were caliciviruses and mamastroviruses (almost exclusively type 10). However, the numbers of reads assigned to caliciviruses were almost 3 times higher in the diarrheic pools compared the non-diarrheic pools and Sapporo-like caliciviruses were more abundant than the Norwalk-like caliciviruses. The results from this study have contributed to the insight into the changes in the intestinal microbiota associated with the PWD syndrome of mink.",2018 Oct 18,"['Birch, Julie Melsted', 'Ullman, Karin', 'Struve, Tina', 'Agger, Jens Frederik', 'Hammer, Anne Sofie', 'Leijon, Mikael', 'Jensen, Henrik Elvang']",PLoS One,,,False
2d43b4f1144dfc389a0b0e3f93e7c44090f4dee9,PMC,Blood immune transcriptome analysis of artificially fed dairy calves and naturally suckled beef calves from birth to 7 days of age,http://dx.doi.org/10.1038/s41598-018-33627-0,PMC6194081,30337646,CC BY,"Neonatal calves possess a very immature and naïve immune system and are reliant on the intake of maternal colostrum for passive transfer of immunoglobulins. Variation in colostrum management of beef and dairy calves is thought to affect early immune development. Therefore, the objective of this study was to examine changes in gene expression and investigate molecular pathways involved in the immune-competence development of neonatal Holstein dairy calves and naturally suckled beef calves using next generation RNA-sequencing during the first week of life. Jugular whole blood samples were collected from Holstein (H) dairy calves (n = 8) artificially fed 5% B.W. colostrum, and from beef calves which were the progenies of Charolais-Limousin (CL; n = 7) and Limousin-Friesian beef suckler cows (LF; n = 7), for subsequent RNA isolation. In dairy calves, there was a surge in pro-inflammatory cytokine gene expression possibly due to the stress of separation from the dam. LF calves exhibited early signs of humoral immune development with observed increases in the expression genes coding for Ig receptors, which was not evident in the other breeds by 7 days of age. Immune and health related DEGs identified as upregulated in beef calves are prospective contender genes for the classification of biomarkers for immune-competence development, and will contribute towards a greater understanding of the development of an immune response in neonatal calves.",2018 Oct 18,"['Surlis, C.', 'Earley, B.', 'McGee, M.', 'Keogh, K.', 'Cormican, P.', 'Blackshields, G.', 'Tiernan, K.', 'Dunn, A.', 'Morrison, S.', 'Arguello, A.', 'Waters, S. M.']",Sci Rep,,,False
62a87de16c26fdb905173879c56ec19a2879921f,PMC,Blood immune transcriptome analysis of artificially fed dairy calves and naturally suckled beef calves from birth to 7 days of age,http://dx.doi.org/10.1038/s41598-018-33627-0,PMC6194081,30337646,CC BY,"Neonatal calves possess a very immature and naïve immune system and are reliant on the intake of maternal colostrum for passive transfer of immunoglobulins. Variation in colostrum management of beef and dairy calves is thought to affect early immune development. Therefore, the objective of this study was to examine changes in gene expression and investigate molecular pathways involved in the immune-competence development of neonatal Holstein dairy calves and naturally suckled beef calves using next generation RNA-sequencing during the first week of life. Jugular whole blood samples were collected from Holstein (H) dairy calves (n = 8) artificially fed 5% B.W. colostrum, and from beef calves which were the progenies of Charolais-Limousin (CL; n = 7) and Limousin-Friesian beef suckler cows (LF; n = 7), for subsequent RNA isolation. In dairy calves, there was a surge in pro-inflammatory cytokine gene expression possibly due to the stress of separation from the dam. LF calves exhibited early signs of humoral immune development with observed increases in the expression genes coding for Ig receptors, which was not evident in the other breeds by 7 days of age. Immune and health related DEGs identified as upregulated in beef calves are prospective contender genes for the classification of biomarkers for immune-competence development, and will contribute towards a greater understanding of the development of an immune response in neonatal calves.",2018 Oct 18,"['Surlis, C.', 'Earley, B.', 'McGee, M.', 'Keogh, K.', 'Cormican, P.', 'Blackshields, G.', 'Tiernan, K.', 'Dunn, A.', 'Morrison, S.', 'Arguello, A.', 'Waters, S. M.']",Sci Rep,,,True
5c8dd07d1f935b762960eff3a7cf7c6f1233ccd3,PMC,Innate Immune Detection of Cardioviruses and Viral Disruption of Interferon Signaling,http://dx.doi.org/10.3389/fmicb.2018.02448,PMC6194174,30369921,CC BY,"Cardioviruses are members of the Picornaviridae family and infect a variety of mammals, from mice to humans. Replication of cardioviruses produces double stranded RNA that is detected by helicases in the RIG-I-like receptor family and leads to a signaling cascade to produce type I interferon. Like other viruses within Picornaviridae, however, cardioviruses have evolved several mechanisms to inhibit interferon production. In this review, we summarize recent findings that have uncovered several proteins enabling efficient detection of cardiovirus dsRNA and discuss which cell types may be most important for interferon production in vivo. Additionally, we describe how cardiovirus proteins L, 3C and L(∗) disrupt interferon production and antagonize the antiviral activity of interferon effector molecules.",2018 Oct 12,"['Freundt, Eric C.', 'Drappier, Melissa', 'Michiels, Thomas']",Front Microbiol,,,True
407efcba93e1b021b6556011cf2f9997ee108a8f,PMC,Patient and health system delays before registration among migrant patients with tuberculosis who were transferred out in China,http://dx.doi.org/10.1186/s12913-018-3583-y,PMC6194607,30340489,CC BY,"BACKGROUND: Early diagnosis and treatment is vital for effective tuberculosis (TB) management especially among migrant populations who are a vulnerable group. We aimed to study factors associated with delay before registration at country level among registered migrant TB patients in China (2014–15) who were transferred out (during treatment) through web-based TB information management system (TBIMS). METHODS: This was a cross sectional study involving review of TBIMS data. Delays (in days) were classified as follows: patient delay (from symptom onset to first doctor visit), health system delay (from first doctor visit to treatment initiation, divided into health system diagnosis and treatment delay before and after date of diagnosis respectively), diagnosis delay (from symptom onset to diagnosis) and total delay (from symptom onset to treatment initiation). Linear regression was used to build a predictive model (forward stepwise) for the socio-demographic, clinical and health system related factors associated with delay: one model for each type of delay. Delays were log transformed and included in the model. RESULTS: The median (IQR) patient delay, health system delay and total delay was 16 (6, 34), two (0, 6) and 22 (11, 41) days respectively. Factors associated with long patient, diagnosis and total delay were: female gender, age ≥ 65 years, sputum smear positive pulmonary TB and registration at referral hospital. Treatment initiation delay was significantly higher among those registered in referral hospitals, unemployed and previously treated. Among migrant patients having permanent residence out of province, health system diagnosis delay was significantly higher while treatment initiation delay after diagnosis was significantly lower when compared to patients having permanent residence within the prefecture. CONCLUSION: Among migrant population with TB, patient delay contributed to the total delay. The factors identified including the need for improved coordination between referral hospitals and national programme have to be addressed if China has to end TB. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12913-018-3583-y) contains supplementary material, which is available to authorized users.",2018 Oct 19,"['Li, Tao', 'Zhang, Hui', 'Shewade, Hemant Deepak', 'Soe, Kyaw Thu', 'Wang, Lixia', 'Du, Xin']",BMC Health Serv Res,,,True
df9b7b29b4b5a14245aea9cc707d52b732052a47,PMC,Molecular detection of enteric viruses and the genetic characterization of porcine astroviruses and sapoviruses in domestic pigs from Slovakian farms,http://dx.doi.org/10.1186/s12917-018-1640-8,PMC6194665,30340595,CC BY,"BACKGROUND: Surveillance and characterization of pig enteric viruses such as transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), rotavirus, astrovirus (PAstV), sapovirus (PSaV), kobuvirus and other agents is essential to evaluate the risks to animal health and determination of economic impacts on pig farming. This study reports the detection and genetic characterization of PAstV, PSaV in healthy and diarrheic domestic pigs and PEDV and TGEV in diarrheic pigs of different age groups. RESULTS: The presence of PAstV and PSaV was studied in 411 rectal swabs collected from healthy (n = 251) and diarrheic (n = 160) pigs of different age categories: suckling (n = 143), weaned (n = 147) and fattening (n = 121) animals on farms in Slovakia. The presence of TGEV and PEDV was investigated in the diarrheic pigs (n = 160). A high presence of PAstV infections was detected in both healthy (94.4%) and diarrheic (91.3%) pigs. PSaV was detected less often, but also equally in clinically healthy (8.4%) and diarrheic (10%) pigs. Neither TGEV nor PEDV was detected in any diarrheic sample. The phylogenetic analysis of a part of the RdRp region revealed the presence of all five lineages of PAstV in Slovakia (PAstV-1 – PAstV-5), with the most frequent lineages being PAstV-2 and PAstV-4. Analysis of partial capsid genome sequences of the PSaVs indicated that virus strains belonged to genogroup GIII. Most of the PSaV sequences from Slovakia clustered with sequences originating from neighbouring countries. CONCLUSIONS: Due to no significant difference between healthy and diarrheic pigs testing of the presence of PAstV and PSaV provides no diagnostic value. Genetic diversity of PAstV was very high as all five lineages were identified in pig farms in Slovakia. PSaV strains were genetically related to the strains circulating in Central European region.",2018 Oct 19,"['Salamunova, Slavomira', 'Jackova, Anna', 'Mandelik, Rene', 'Novotny, Jaroslav', 'Vlasakova, Michaela', 'Vilcek, Stefan']",BMC Vet Res,,,True
17192bd07c09aa9e70552f7f15f90f0a6b8180c6,PMC,Overlapping genes and the proteins they encode differ significantly in their sequence composition from non-overlapping genes,http://dx.doi.org/10.1371/journal.pone.0202513,PMC6195259,30339683,CC0,"Overlapping genes represent a fascinating evolutionary puzzle, since they encode two functionally unrelated proteins from the same DNA sequence. They originate by a mechanism of overprinting, in which point mutations in an existing frame allow the expression (the ""birth"") of a completely new protein from a second frame. In viruses, in which overlapping genes are abundant, these new proteins often play a critical role in infection, yet they are frequently overlooked during genome annotation. This results in erroneous interpretation of mutational studies and in a significant waste of resources. Therefore, overlapping genes need to be correctly detected, especially since they are now thought to be abundant also in eukaryotes. Developing better detection methods and conducting systematic evolutionary studies require a large, reliable benchmark dataset of known cases. We thus assembled a high-quality dataset of 80 viral overlapping genes whose expression is experimentally proven. Many of them were not present in databases. We found that overall, overlapping genes differ significantly from non-overlapping genes in their nucleotide and amino acid composition. In particular, the proteins they encode are enriched in high-degeneracy amino acids and depleted in low-degeneracy ones, which may alleviate the evolutionary constraints acting on overlapping genes. Principal component analysis revealed that the vast majority of overlapping genes follow a similar composition bias, despite their heterogeneity in length and function. Six proven mammalian overlapping genes also followed this bias. We propose that this apparently near-universal composition bias may either favour the birth of overlapping genes, or/and result from selection pressure acting on them.",2018 Oct 19,"['Pavesi, Angelo', 'Vianelli, Alberto', 'Chirico, Nicola', 'Bao, Yiming', 'Blinkova, Olga', 'Belshaw, Robert', 'Firth, Andrew', 'Karlin, David']",PLoS One,,,True
1e88d68fd702c8accc72cece9a8df345c64b0b8c,PMC,Characterization of murine CEACAM1 in vivo reveals low expression on CD8(+) T cells and no tumor growth modulating activity by anti-CEACAM1 mAb CC1,http://dx.doi.org/10.18632/oncotarget.26108,PMC6195382,30349641,CC BY,"Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been reported to mediate both tumorigenic and anti-tumor effects in vivo. Blockade of the CEACAM1 signaling pathway has recently been implicated as a novel mechanism for cancer immunotherapy. CC1, a mouse anti-CEACAM1 monoclonal antibody (mAb), has been widely used as a pharmacological tool in preclinical studies to inform on CEACAM1 pathway biology although limited data are available on its CEACAM1 blocking characteristics or pharmacodynamic-pharmacokinetic profiles. We sought to investigate CEACAM1 expression on mouse tumor and immune cells, characterize CC1 mAb binding, and evaluate CC1 in syngeneic mouse oncology models as a monotherapy and in combination with an anti-PD-1 mAb. CEACAM1 expression was observed at high levels on neutrophils, NK cells and myeloid-derived suppressor cells (MDSCs), while the expression on tumor-infiltrating CD8+ T cells was low. Unexpectedly, rather than blocking, CC1 facilitated binding of soluble CEACAM1 to CEACAM1 expressing cells. No anti-tumor effects were observed in CT26, MBT2 or A20 models when tested up to 30 mg/kg dose, a dose that was estimated to achieve >90% target engagement in vivo. Taken together, tumor infiltrating CD8+ T cells express low levels of CEACAM1 and CC1 Ab mediates no or minimal anti-tumor effects in vivo, as a monotherapy or in combination with anti-PD-1 treatment.",2018 Oct 2,"['McLeod, Robbie L.', 'Angagaw, Minilik H.', 'Baral, Toya Nath', 'Liu, Liming', 'Moniz, Raymond Joseph', 'Laskey, Jason', 'Hsieh, SuChun', 'Lee, Mike', 'Han, Jin-Hwan', 'Issafras, Hassan', 'Javaid, Sarah', 'Loboda, Andrey', 'Sadekova, Svetlana', ""O'Connor, Joann A."", 'Tse, Archie', 'Punnonen, Juha']",Oncotarget,,,True
02610c838845176ed2d97c20f415843e1b5edcc1,PMC,Deep sequencing of primary human lung epithelial cells challenged with H5N1 influenza virus reveals a proviral role for CEACAM1,http://dx.doi.org/10.1038/s41598-018-33605-6,PMC6195505,30341336,CC BY,"Current prophylactic and therapeutic strategies targeting human influenza viruses include vaccines and antivirals. Given variable rates of vaccine efficacy and antiviral resistance, alternative strategies are urgently required to improve disease outcomes. Here we describe the use of HiSeq deep sequencing to analyze host gene expression in primary human alveolar epithelial type II cells infected with highly pathogenic avian influenza H5N1 virus. At 24 hours post-infection, 623 host genes were significantly upregulated, including the cell adhesion molecule CEACAM1. H5N1 virus infection stimulated significantly higher CEACAM1 protein expression when compared to influenza A PR8 (H1N1) virus, suggesting a key role for CEACAM1 in influenza virus pathogenicity. Furthermore, silencing of endogenous CEACAM1 resulted in reduced levels of proinflammatory cytokine/chemokine production, as well as reduced levels of virus replication following H5N1 infection. Our study provides evidence for the involvement of CEACAM1 in a clinically relevant model of H5N1 infection and may assist in the development of host-oriented antiviral strategies.",2018 Oct 19,"['Ye, Siying', 'Cowled, Christopher J.', 'Yap, Cheng-Hon', 'Stambas, John']",Sci Rep,,,False
ef58c6e981a08c85d2c0efb80e5b32b075f660b4,PMC,Deep sequencing of primary human lung epithelial cells challenged with H5N1 influenza virus reveals a proviral role for CEACAM1,http://dx.doi.org/10.1038/s41598-018-33605-6,PMC6195505,30341336,CC BY,"Current prophylactic and therapeutic strategies targeting human influenza viruses include vaccines and antivirals. Given variable rates of vaccine efficacy and antiviral resistance, alternative strategies are urgently required to improve disease outcomes. Here we describe the use of HiSeq deep sequencing to analyze host gene expression in primary human alveolar epithelial type II cells infected with highly pathogenic avian influenza H5N1 virus. At 24 hours post-infection, 623 host genes were significantly upregulated, including the cell adhesion molecule CEACAM1. H5N1 virus infection stimulated significantly higher CEACAM1 protein expression when compared to influenza A PR8 (H1N1) virus, suggesting a key role for CEACAM1 in influenza virus pathogenicity. Furthermore, silencing of endogenous CEACAM1 resulted in reduced levels of proinflammatory cytokine/chemokine production, as well as reduced levels of virus replication following H5N1 infection. Our study provides evidence for the involvement of CEACAM1 in a clinically relevant model of H5N1 infection and may assist in the development of host-oriented antiviral strategies.",2018 Oct 19,"['Ye, Siying', 'Cowled, Christopher J.', 'Yap, Cheng-Hon', 'Stambas, John']",Sci Rep,,,True
37967ef8f5f2879e3c364ebd5a6e11bf3bc8b7d3,PMC,White-nose syndrome is associated with increased replication of a naturally persisting coronaviruses in bats,http://dx.doi.org/10.1038/s41598-018-33975-x,PMC6195612,30341341,CC BY,"Spillover of viruses from bats to other animals may be associated with increased contact between them, as well as increased shedding of viruses by bats. Here, we tested the prediction that little brown bats (Myotis lucifugus) co-infected with the M. lucifugus coronavirus (Myl-CoV) and with Pseudogymnoascus destructans (Pd), the fungus that causes bat white-nose syndrome (WNS), exhibit different disease severity, viral shedding and molecular responses than bats infected with only Myl-CoV or only P. destructans. We took advantage of the natural persistence of Myl-CoV in bats that were experimentally inoculated with P. destructans in a previous study. Here, we show that the intestines of virus-infected bats that were also infected with fungus contained on average 60-fold more viral RNA than bats with virus alone. Increased viral RNA in the intestines correlated with the severity of fungus-related pathology. Additionally, the intestines of bats infected with fungus exhibited different expression of mitogen-activated protein kinase pathway and cytokine related transcripts, irrespective of viral presence. Levels of coronavirus antibodies were also higher in fungal-infected bats. Our results suggest that the systemic effects of WNS may down-regulate anti-viral responses in bats persistently infected with M. lucifugus coronavirus and increase the potential of virus shedding.",2018 Oct 19,"['Davy, Christina M.', 'Donaldson, Michael E.', 'Subudhi, Sonu', 'Rapin, Noreen', 'Warnecke, Lisa', 'Turner, James M.', 'Bollinger, Trent K.', 'Kyle, Christopher J.', 'Dorville, Nicole A. S.-Y.', 'Kunkel, Emma L.', 'Norquay, Kaleigh J. O.', 'Dzal, Yvonne A.', 'Willis, Craig K. R.', 'Misra, Vikram']",Sci Rep,,,False
d495854289e2ffd80ba9ac86688abe6c7577b545,PMC,White-nose syndrome is associated with increased replication of a naturally persisting coronaviruses in bats,http://dx.doi.org/10.1038/s41598-018-33975-x,PMC6195612,30341341,CC BY,"Spillover of viruses from bats to other animals may be associated with increased contact between them, as well as increased shedding of viruses by bats. Here, we tested the prediction that little brown bats (Myotis lucifugus) co-infected with the M. lucifugus coronavirus (Myl-CoV) and with Pseudogymnoascus destructans (Pd), the fungus that causes bat white-nose syndrome (WNS), exhibit different disease severity, viral shedding and molecular responses than bats infected with only Myl-CoV or only P. destructans. We took advantage of the natural persistence of Myl-CoV in bats that were experimentally inoculated with P. destructans in a previous study. Here, we show that the intestines of virus-infected bats that were also infected with fungus contained on average 60-fold more viral RNA than bats with virus alone. Increased viral RNA in the intestines correlated with the severity of fungus-related pathology. Additionally, the intestines of bats infected with fungus exhibited different expression of mitogen-activated protein kinase pathway and cytokine related transcripts, irrespective of viral presence. Levels of coronavirus antibodies were also higher in fungal-infected bats. Our results suggest that the systemic effects of WNS may down-regulate anti-viral responses in bats persistently infected with M. lucifugus coronavirus and increase the potential of virus shedding.",2018 Oct 19,"['Davy, Christina M.', 'Donaldson, Michael E.', 'Subudhi, Sonu', 'Rapin, Noreen', 'Warnecke, Lisa', 'Turner, James M.', 'Bollinger, Trent K.', 'Kyle, Christopher J.', 'Dorville, Nicole A. S.-Y.', 'Kunkel, Emma L.', 'Norquay, Kaleigh J. O.', 'Dzal, Yvonne A.', 'Willis, Craig K. R.', 'Misra, Vikram']",Sci Rep,,,True
7927b8f05155e6933aaf8d9509dbd379d017dfe7,PMC,Transferrin receptor 1 is a supplementary receptor that assists transmissible gastroenteritis virus entry into porcine intestinal epithelium,http://dx.doi.org/10.1186/s12964-018-0283-5,PMC6196004,30342530,CC BY,"BACKGROUND: Transmissible gastroenteritis virus (TGEV), the etiologic agent of transmissible gastroenteritis, infects swine of all ages causing vomiting and diarrhea, in newborn piglets the mortality rate is near 100%. Intestinal epithelial cells are the primary target cells of TGEV. Transferrin receptor 1 (TfR1), which is highly expressed in piglets with anemia, may play a role in TGEV infection. However, the underlying mechanism of TGEV invasion remains largely unknown. RESULTS: Our study investigated the possibility that TfR1 can serve as a receptor for TGEV infection and enables the invasion and replication of TGEV. We observed that TGEV infection promoted TfR1 internalization, clustering, and co-localization with TfR1 early in infection, while TfR1 expression was significantly down-regulated as TGEV infection proceeded. TGEV infection and replication were inhibited by occluding TfR1 with antibodies or by decreasing TfR1 expression. TGEV infection increased in TGEV-susceptible ST or IPEC-J2 cell lines and TGEV-resistant Caco-2 cells when porcine TfR1 was over-expressed. Finally, we found that the TGEV S1 protein interacts with the extracellular region of TfR1, and that pre-incubating TGEV with a protein fragment containing the extracellular region of TfR1 blocked viral infection. CONCLUSIONS: Our results support the hypothesis that TfR1 is an additional receptor for TGEV and assists TGEV invasion and replication. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12964-018-0283-5) contains supplementary material, which is available to authorized users.",2018 Oct 20,"['Zhang, Shuai', 'Hu, Weiwei', 'Yuan, Lvfeng', 'Yang, Qian']",Cell Commun Signal,,,True
3a3c6a9ff71461bd81862fc711d5605cfbbb975d,PMC,outbreaker2: a modular platform for outbreak reconstruction,http://dx.doi.org/10.1186/s12859-018-2330-z,PMC6196407,30343663,CC BY,"BACKGROUND: Reconstructing individual transmission events in an infectious disease outbreak can provide valuable information and help inform infection control policy. Recent years have seen considerable progress in the development of methodologies for reconstructing transmission chains using both epidemiological and genetic data. However, only a few of these methods have been implemented in software packages, and with little consideration for customisability and interoperability. Users are therefore limited to a small number of alternatives, incompatible tools with fixed functionality, or forced to develop their own algorithms at considerable personal effort. RESULTS: Here we present outbreaker2, a flexible framework for outbreak reconstruction. This R package re-implements and extends the original model introduced with outbreaker, but most importantly also provides a modular platform allowing users to specify custom models within an optimised inferential framework. As a proof of concept, we implement the within-host evolutionary model introduced with TransPhylo, which is very distinct from the original genetic model in outbreaker, and demonstrate how even complex model results can be successfully included with minimal effort. CONCLUSIONS: outbreaker2 provides a valuable starting point for future outbreak reconstruction tools, and represents a unifying platform that promotes customisability and interoperability. Implemented in the R software, outbreaker2 joins a growing body of tools for outbreak analysis.",2018 Oct 22,"['Campbell, Finlay', 'Didelot, Xavier', 'Fitzjohn, Rich', 'Ferguson, Neil', 'Cori, Anne', 'Jombart, Thibaut']",BMC Bioinformatics,,,True
7ec733f3684d6294483b03df183878ad777a78d9,PMC,Future Path Toward TB Vaccine Development: Boosting BCG or Re-educating by a New Subunit Vaccine,http://dx.doi.org/10.3389/fimmu.2018.02371,PMC6198790,30386336,CC BY,"Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb), kills 5,000 people per day globally. Rapid development and spread of various multi drug-resistant strains of Mtb emphasize that an effective vaccine is still the most cost-effectives and efficient way of controlling and eradicating TB. Bacillus Calmette-Guerin (BCG), the only licensed TB vaccine, still remains the most widely administered human vaccine, but is inefficient in protecting from pulmonary TB in adults. The protective immunity afforded by BCG is thought to wane with time and considered to last only through adolescent years. Heterologous boosting of BCG-primed immune responses using a subunit vaccine represents a promising vaccination approach to promote strong cellular responses against Mtb. In our earlier studies, we discovered lipopeptides of ESAT-6 antigen with strong potential as a subunit vaccine candidate. Here, we have investigated that potential as a booster to BCG vaccine in both a pre-exposure preventive vaccine and a post-exposure therapeutic vaccine setting. Surprisingly, our results demonstrated that boosting BCG with subunit vaccine shortly before Mtb challenge did not improve the BCG-primed immunity, whereas the subunit vaccine boost after Mtb challenge markedly improved the quantity and quality of effector T cell responses and significantly reduced Mtb load in lungs, liver and spleen in mice. These studies suggest that ESAT-6 lipopeptide-based subunit vaccine was ineffective in overcoming the apparent immunomodulation induced by BCG vaccine in Mtb uninfected mice, but upon infection, the subunit vaccine is effective in re-educating the protective immunity against Mtb infection. These important results have significant implications in the design and investigation of effective vaccine strategies and immunotherapeutic approaches for individuals who have been pre-immunized with BCG vaccine but still get infected with Mtb.",2018 Oct 16,"['Gupta, Nancy', 'Garg, Saurabh', 'Vedi, Satish', 'Kunimoto, Dennis Y.', 'Kumar, Rakesh', 'Agrawal, Babita']",Front Immunol,,,True
86a11741a321a657e22fd7d94af6193d27cc6f5f,PMC,Clinical characteristics of patients with laboratory-confirmed influenza A(H1N1)pdm09 during the 2013/2014 and 2015/2016 clade 6B/6B.1/6B.2-predominant outbreaks,http://dx.doi.org/10.1038/s41598-018-34077-4,PMC6199313,30353096,CC BY,"A novel pandemic influenza A(H1N1)pdm09 virus emerged in 2009 globally, and it continues to circulate in humans. The National Influenza Surveillance Network in Taiwan identified five A(H1N1)pdm09-predominant seasons, representing the 2009/2010, 2010/2011, 2012/2013, 2013/2014, and 2015/2016 outbreaks from 2009 to 2016. Independently, a retrospective cohort study (which enrolled 639 infected patients during the five seasons) was conducted at Chang Gung Memorial Hospital to explore the risk factors associated with influenza A(H1N1)pdm09-related complications. A phylogenetic analysis of hemagglutinin (HA) sequences showed that the circulating A(H1N1)pdm09 virus belonged to clades 1, 2, and 8 in 2009/2010; clades 3, 4, 5, and 7 in 2010/2011; clades 7 and 6C in 2012/2013; clades 6B in 2013/2014; and 6B/6B.1/6B.2 in 2015/2016. Compared to individuals infected in non-6B/6B.1/6B.2 seasons (2009/2010, 2010/2011, and 2012/2013), those infected in 6B/6B.1/6B.2 seasons (2013/2014 and 2015/2016) were at higher risk for influenza-related complications (adjusted odds ratio [aOR]: 1.6, 95% confidence interval [CI]: 1.0–2.8), pneumonia (aOR: 1.78, 95% CI: 1.04–3.04), mechanical ventilation (aOR: 2.6, 95% CI: 1.2–5.6), and acute respiratory distress syndrome (aOR: 5.5, 95% CI: 1.9–15.9). For the increased severity of infection during the influenza A(H1N1)pdm09 clade 6B/6B.1/6B.2 seasons, aspects related to the antigenic change of A(H1N1)pdm09 virus, immune response of the host, and environmental factors required further investigation.",2018 Oct 23,"['Hsieh, Yu-Chia', 'Tsao, Kuo-Chien', 'Huang, Ching-Tai', 'Chang, Kuang-Yi', 'Huang, Yhu-Chering', 'Gong, Yu-Nong']",Sci Rep,,,True
751163b36576e3b25e90b10c33528efc89204313,PMC,SMS-based smartphone application for disease surveillance has doubled completeness and timeliness in a limited-resource setting – evaluation of a 15-week pilot program in Central African Republic (CAR),http://dx.doi.org/10.1186/s13031-018-0177-6,PMC6199707,30386418,CC BY,"BACKGROUND: It is a challenge in low-resource settings to ensure the availability of complete, timely disease surveillance information. Smartphone applications (apps) have the potential to enhance surveillance data transmission. METHODS: The Central African Republic (CAR) Ministry of Health and Médecins Sans Frontières (MSF) conducted a 15-week pilot project to test a disease surveillance app, Argus, for 20 conditions in 21 health centers in Mambéré Kadéi district (MK 2016). Results were compared to the usual paper-based surveillance in MK the year prior (MK 2015) and simultaneously in an adjacent health district, Nana-Mambére (NM 2016). Wilcoxon rank sum and Kaplan-Meier analyses compared report completeness and timeliness; the cost of the app, and users’ perceptions of its usability were assessed. RESULTS: Two hundred seventy-one weekly reports sent by app identified 3403 cases and 63 deaths; 15 alerts identified 28 cases and 4 deaths. Median completeness (IQR) for MK 2016, 81% (81–86%), was significantly higher than in MK 2015 (31% (24–36%)), and NM 2016 (52% (48–57)) (p < 0.01). Median timeliness (IQR) for MK 2016, 50% (39–57%) was also higher than in MK 2015, 19% (19–24%), and NM 2016 29% (24–36%) (p < 0.01). Kaplan-Meier Survival Analysis showed a significant progressive reduction in the time taken to transmit reports over the 15-week period (p < 0.01). Users ranked the app’s usability as greater than 4/5 on all dimensions. The total cost of the 15-week pilot project was US$40,575. It is estimated that to maintain the app in the 21 health facilities of MK will cost approximately US$18,800 in communication fees per year. CONCLUSIONS: The app-based data transmission system more than doubled the completeness and timeliness of disease surveillance reports. This simple, low-cost intervention may permit the early detection of disease outbreaks in similar low-resource settings elsewhere.",2018 Oct 24,"['El-Khatib, Ziad', 'Shah, Maya', 'Zallappa, Samuel N', 'Nabeth, Pierre', 'Guerra, José', 'Manengu, Casimir T', 'Yao, Michel', 'Philibert, Aline', 'Massina, Lazare', 'Staiger, Claes-Philip', 'Mbailao, Raphael', 'Kouli, Jean-Pierre', 'Mboma, Hippolyte', 'Duc, Geraldine', 'Inagbe, Dago', 'Barry, Alpha Boubaca', 'Dumont, Thierry', 'Cavailler, Philippe', 'Quere, Michel', 'Willett, Brian', 'Reaiche, Souheil', 'de Ribaucourt, Hervé', 'Reeder, Bruce']",Confl Health,,,True
05c54da3a4bd3e92c4d0e5286e331e333408c9a9,PMC,Identification of a novel nidovirus as a potential cause of large scale mortalities in the endangered Bellinger River snapping turtle (Myuchelys georgesi),http://dx.doi.org/10.1371/journal.pone.0205209,PMC6200216,30356240,CC BY,"In mid-February 2015, a large number of deaths were observed in the sole extant population of an endangered species of freshwater snapping turtle, Myuchelys georgesi, in a coastal river in New South Wales, Australia. Mortalities continued for approximately 7 weeks and affected mostly adult animals. More than 400 dead or dying animals were observed and population surveys conducted after the outbreak had ceased indicated that only a very small proportion of the population had survived, severely threatening the viability of the wild population. At necropsy, animals were in poor body condition, had bilateral swollen eyelids and some animals had tan foci on the skin of the ventral thighs. Histological examination revealed peri-orbital, splenic and nephric inflammation and necrosis. A virus was isolated in cell culture from a range of tissues. Nucleic acid sequencing of the virus isolate has identified the entire genome and indicates that this is a novel nidovirus that has a low level of nucleotide similarity to recognised nidoviruses. Its closest relatives are nidoviruses that have recently been described in pythons and lizards, usually in association with respiratory disease. In contrast, in the affected turtles, the most significant pathological changes were in the kidneys. Real time PCR assays developed to detect this virus demonstrated very high virus loads in affected tissues. In situ hybridisation studies confirmed the presence of viral nucleic acid in tissues in association with pathological changes. Collectively these data suggest that this virus is the likely cause of the mortalities that now threaten the survival of this species. Bellinger River Virus is the name proposed for this new virus.",2018 Oct 24,"['Zhang, Jing', 'Finlaison, Deborah S.', 'Frost, Melinda J.', 'Gestier, Sarah', 'Gu, Xingnian', 'Hall, Jane', 'Jenkins, Cheryl', 'Parrish, Kate', 'Read, Andrew J.', 'Srivastava, Mukesh', 'Rose, Karrie', 'Kirkland, Peter D.']",PLoS One,,,True
80e99b5d07493e544deeeab6db940ca7ab8a3c48,PMC,Identification of a novel nidovirus as a potential cause of large scale mortalities in the endangered Bellinger River snapping turtle (Myuchelys georgesi),http://dx.doi.org/10.1371/journal.pone.0205209,PMC6200216,30356240,CC BY,"In mid-February 2015, a large number of deaths were observed in the sole extant population of an endangered species of freshwater snapping turtle, Myuchelys georgesi, in a coastal river in New South Wales, Australia. Mortalities continued for approximately 7 weeks and affected mostly adult animals. More than 400 dead or dying animals were observed and population surveys conducted after the outbreak had ceased indicated that only a very small proportion of the population had survived, severely threatening the viability of the wild population. At necropsy, animals were in poor body condition, had bilateral swollen eyelids and some animals had tan foci on the skin of the ventral thighs. Histological examination revealed peri-orbital, splenic and nephric inflammation and necrosis. A virus was isolated in cell culture from a range of tissues. Nucleic acid sequencing of the virus isolate has identified the entire genome and indicates that this is a novel nidovirus that has a low level of nucleotide similarity to recognised nidoviruses. Its closest relatives are nidoviruses that have recently been described in pythons and lizards, usually in association with respiratory disease. In contrast, in the affected turtles, the most significant pathological changes were in the kidneys. Real time PCR assays developed to detect this virus demonstrated very high virus loads in affected tissues. In situ hybridisation studies confirmed the presence of viral nucleic acid in tissues in association with pathological changes. Collectively these data suggest that this virus is the likely cause of the mortalities that now threaten the survival of this species. Bellinger River Virus is the name proposed for this new virus.",2018 Oct 24,"['Zhang, Jing', 'Finlaison, Deborah S.', 'Frost, Melinda J.', 'Gestier, Sarah', 'Gu, Xingnian', 'Hall, Jane', 'Jenkins, Cheryl', 'Parrish, Kate', 'Read, Andrew J.', 'Srivastava, Mukesh', 'Rose, Karrie', 'Kirkland, Peter D.']",PLoS One,,,False
bb99b6dde050807939930f078e0eed8a4693a710,PMC,"A comprehensive in silico analysis for identification of therapeutic epitopes in HPV16, 18, 31 and 45 oncoproteins",http://dx.doi.org/10.1371/journal.pone.0205933,PMC6200245,30356257,CC BY,"Human papillomaviruses (HPVs) are a group of circular double-stranded DNA viruses, showing severe tropism to mucosal tissues. A subset of HPVs, especially HPV16 and 18, are the primary etiological cause for several epithelial cell malignancies, causing about 5.2% of all cancers worldwide. Due to the high prevalence and mortality, HPV-associated cancers have remained as a significant health problem in human society, making an urgent need to develop an effective therapeutic vaccine against them. Achieving this goal is primarily dependent on the identification of efficient tumor-associated epitopes, inducing a robust cell-mediated immune response. Previous information has shown that E5, E6, and E7 early proteins are responsible for the induction and maintenance of HPV-associated cancers. Therefore, the prediction of major histocompatibility complex (MHC) class I T cell epitopes of HPV16, 18, 31 and 45 oncoproteins was targeted in this study. For this purpose, a two-step plan was designed to identify the most probable CD8+ T cell epitopes. In the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and in the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens’ analyses were carried out successively by different tools. Finally, we introduced five probable CD8+ T cell epitopes for each oncoprotein of the HPV genotypes (60 epitopes in total), which obtained better scores by an integrated approach. These predicted epitopes are valuable candidates for in vitro or in vivo therapeutic vaccine studies against the HPV-associated cancers. Additionally, this two-step plan that each step includes several analyses to find appropriate epitopes provides a rational basis for DNA- or peptide-based vaccine development.",2018 Oct 24,"['Panahi, Heidar Ali', 'Bolhassani, Azam', 'Javadi, Gholamreza', 'Noormohammadi, Zahra']",PLoS One,,,True
7b830ff35cb63eec2889a5d21a0d49d1f8c687c3,PMC,Overexpression of the nucleocapsid protein of Middle East respiratory syndrome coronavirus up-regulates CXCL10,http://dx.doi.org/10.1042/BSR20181059,PMC6200698,30242057,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory diseases in humans and has a high mortality rate. During infection, MERS-CoV regulates several host cellular processes including antiviral response genes. In order to determine if the nucleocapsid protein of MERS-CoV (MERS-N) plays a role in viral–host interactions, a murine monoclonal antibody was generated so as to allow detection of the protein in infected cells as well as in overexpression system. Then, MERS-N was stably overexpressed in A549 cells, and a PCR array containing 84 genes was used to screen for genes transcriptionally regulated by it. Several up-regulated antiviral genes, namely TNF, IL6, IL8, and CXCL10, were selected for independent validation in transiently transfected 293FT cells. Out of these, the overexpression of MERS-N was found to up-regulate CXCL10 at both transcriptional and translational levels. Interestingly, CXCL10 has been reported to be up-regulated in MERS-CoV infected airway epithelial cells and lung fibroblast cells, as well as monocyte-derived macrophages and dendritic cells. High secretions and persistent increase of CXCL10 in MERS-CoV patients have been also associated with severity of disease. To our knowledge, this is the first report showing that the MERS-N protein is one of the contributing factors for CXCL10 up-regulation during infection. In addition, our results showed that a fragment consisting of residues 196–413 in MERS-N is sufficient to up-regulate CXCL10, while the N-terminal domain and serine-arginine (SR)-rich motif of MERS-N do not play a role in this up-regulation.",2018 Oct 17,"['Aboagye, James\xa0Odame', 'Yew, Chow\xa0Wenn', 'Ng, Oi-Wing', 'Monteil, Vanessa\xa0M.', 'Mirazimi, Ali', 'Tan, Yee-Joo']",Biosci Rep,,,False
9d941db9f06f446ae113c5f76f7597553a2f365b,PMC,Overexpression of the nucleocapsid protein of Middle East respiratory syndrome coronavirus up-regulates CXCL10,http://dx.doi.org/10.1042/BSR20181059,PMC6200698,30242057,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory diseases in humans and has a high mortality rate. During infection, MERS-CoV regulates several host cellular processes including antiviral response genes. In order to determine if the nucleocapsid protein of MERS-CoV (MERS-N) plays a role in viral–host interactions, a murine monoclonal antibody was generated so as to allow detection of the protein in infected cells as well as in overexpression system. Then, MERS-N was stably overexpressed in A549 cells, and a PCR array containing 84 genes was used to screen for genes transcriptionally regulated by it. Several up-regulated antiviral genes, namely TNF, IL6, IL8, and CXCL10, were selected for independent validation in transiently transfected 293FT cells. Out of these, the overexpression of MERS-N was found to up-regulate CXCL10 at both transcriptional and translational levels. Interestingly, CXCL10 has been reported to be up-regulated in MERS-CoV infected airway epithelial cells and lung fibroblast cells, as well as monocyte-derived macrophages and dendritic cells. High secretions and persistent increase of CXCL10 in MERS-CoV patients have been also associated with severity of disease. To our knowledge, this is the first report showing that the MERS-N protein is one of the contributing factors for CXCL10 up-regulation during infection. In addition, our results showed that a fragment consisting of residues 196–413 in MERS-N is sufficient to up-regulate CXCL10, while the N-terminal domain and serine-arginine (SR)-rich motif of MERS-N do not play a role in this up-regulation.",2018 Oct 17,"['Aboagye, James\xa0Odame', 'Yew, Chow\xa0Wenn', 'Ng, Oi-Wing', 'Monteil, Vanessa\xa0M.', 'Mirazimi, Ali', 'Tan, Yee-Joo']",Biosci Rep,,,True
ec09394ffef7660b3a7013dda8e10786bb51e3d6,PMC,Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis,http://dx.doi.org/10.1038/s41598-018-34171-7,PMC6200764,30356097,CC BY,"Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 as a highly transmissible pathogenic human betacoronavirus. The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism. As SARS-CoV enters host cells, the viral S is believed to undergo a number of conformational transitions as it is cleaved by host proteases and binds to host receptors. We recently developed stabilizing mutations for coronavirus spikes that prevent the transition from the pre-fusion to post-fusion states. Here, we present cryo-EM analyses of a stabilized trimeric SARS-CoV S, as well as the trypsin-cleaved, stabilized S, and its interactions with ACE2. Neither binding to ACE2 nor cleavage by trypsin at the S1/S2 cleavage site impart large conformational changes within stabilized SARS-CoV S or expose the secondary cleavage site, S2′.",2018 Oct 24,"['Kirchdoerfer, Robert N.', 'Wang, Nianshuang', 'Pallesen, Jesper', 'Wrapp, Daniel', 'Turner, Hannah L.', 'Cottrell, Christopher A.', 'Corbett, Kizzmekia S.', 'Graham, Barney S.', 'McLellan, Jason S.', 'Ward, Andrew B.']",Sci Rep,,,True
773219a6abb0977144db395a5d94f63ce2eb03c6,PMC,Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis,http://dx.doi.org/10.1038/s41598-018-34171-7,PMC6200764,30356097,CC BY,"Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 as a highly transmissible pathogenic human betacoronavirus. The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism. As SARS-CoV enters host cells, the viral S is believed to undergo a number of conformational transitions as it is cleaved by host proteases and binds to host receptors. We recently developed stabilizing mutations for coronavirus spikes that prevent the transition from the pre-fusion to post-fusion states. Here, we present cryo-EM analyses of a stabilized trimeric SARS-CoV S, as well as the trypsin-cleaved, stabilized S, and its interactions with ACE2. Neither binding to ACE2 nor cleavage by trypsin at the S1/S2 cleavage site impart large conformational changes within stabilized SARS-CoV S or expose the secondary cleavage site, S2′.",2018 Oct 24,"['Kirchdoerfer, Robert N.', 'Wang, Nianshuang', 'Pallesen, Jesper', 'Wrapp, Daniel', 'Turner, Hannah L.', 'Cottrell, Christopher A.', 'Corbett, Kizzmekia S.', 'Graham, Barney S.', 'McLellan, Jason S.', 'Ward, Andrew B.']",Sci Rep,,,True
107df8f8ca73520a287e12ed04bd7ee29cee72af,PMC,Laboratory Diagnosis of Respiratory Tract Infections in Children – the State of the Art,http://dx.doi.org/10.3389/fmicb.2018.02478,PMC6200861,30405553,CC BY,"In the pediatric population, respiratory infections are the most common cause of physician visits. Although many respiratory illnesses are self-limiting viral infections that resolve with time and supportive care, it can be critical to identify the causative pathogen at an early stage of the disease in order to implement effective antimicrobial therapy and infection control. Over the last few years, diagnostics for respiratory infections have evolved substantially, with the development of novel assays and the availability of updated tests for newer strains of pathogens. Newer laboratory methods are rapid, highly sensitive and specific, and are gradually replacing the conventional gold standards, although the clinical utility of these assays is still under evaluation. This article reviews the current laboratory methods available for testing for respiratory pathogens and discusses the advantages and disadvantages of each approach.",2018 Oct 18,"['Das, Shubhagata', 'Dunbar, Sherry', 'Tang, Yi-Wei']",Front Microbiol,,,True
21a9444b2cd05fcac9c082ca87fac36e91086b6c,PMC,The Small-Compound Inhibitor K22 Displays Broad Antiviral Activity against Different Members of the Family Flaviviridae and Offers Potential as a Panviral Inhibitor,http://dx.doi.org/10.1128/AAC.01206-18,PMC6201103,30181371,CC BY,"The virus family Flaviviridae encompasses several viruses, including (re)emerging viruses which cause widespread morbidity and mortality throughout the world. Members of this virus family are positive-strand RNA viruses and replicate their genome in close association with reorganized intracellular host cell membrane compartments. This evolutionarily conserved strategy facilitates efficient viral genome replication and contributes to evasion from host cell cytosolic defense mechanisms. We have previously described the identification of a small-compound inhibitor, K22, which exerts a potent antiviral activity against a broad range of coronaviruses by targeting membrane-bound viral RNA replication. To analyze the antiviral spectrum of this inhibitor, we assessed the inhibitory potential of K22 against several members of the Flaviviridae family, including the reemerging Zika virus (ZIKV). We show that ZIKV is strongly affected by K22. Time-of-addition experiments revealed that K22 acts during a postentry phase of the ZIKV life cycle, and combination regimens of K22 together with ribavirin (RBV) or interferon alpha (IFN-α) further increased the extent of viral inhibition. Ultrastructural electron microscopy studies revealed severe alterations of ZIKV-induced intracellular replication compartments upon infection of K22-treated cells. Importantly, the antiviral activity of K22 was demonstrated against several other members of the Flaviviridae family. It is tempting to speculate that K22 exerts its broad antiviral activity against several positive-strand RNA viruses via a similar mechanism and thereby represents an attractive candidate for development as a panviral inhibitor.",2018 Oct 24,"['García-Nicolás, Obdulio', ""V'kovski, Philip"", 'Vielle, Nathalie J.', 'Ebert, Nadine', 'Züst, Roland', 'Portmann, Jasmine', 'Stalder, Hanspeter', 'Gaschen, Véronique', 'Vieyres, Gabrielle', 'Stoffel, Michael', 'Schweizer, Matthias', 'Summerfield, Artur', 'Engler, Olivier', 'Pietschmann, Thomas', 'Todt, Daniel', 'Alves, Marco P.', 'Thiel, Volker', 'Pfaender, Stephanie']",Antimicrob Agents Chemother,,,True
a2d6bda7ebe47fde9c537263947f66af2168d4b9,PMC,The Small-Compound Inhibitor K22 Displays Broad Antiviral Activity against Different Members of the Family Flaviviridae and Offers Potential as a Panviral Inhibitor,http://dx.doi.org/10.1128/AAC.01206-18,PMC6201103,30181371,CC BY,"The virus family Flaviviridae encompasses several viruses, including (re)emerging viruses which cause widespread morbidity and mortality throughout the world. Members of this virus family are positive-strand RNA viruses and replicate their genome in close association with reorganized intracellular host cell membrane compartments. This evolutionarily conserved strategy facilitates efficient viral genome replication and contributes to evasion from host cell cytosolic defense mechanisms. We have previously described the identification of a small-compound inhibitor, K22, which exerts a potent antiviral activity against a broad range of coronaviruses by targeting membrane-bound viral RNA replication. To analyze the antiviral spectrum of this inhibitor, we assessed the inhibitory potential of K22 against several members of the Flaviviridae family, including the reemerging Zika virus (ZIKV). We show that ZIKV is strongly affected by K22. Time-of-addition experiments revealed that K22 acts during a postentry phase of the ZIKV life cycle, and combination regimens of K22 together with ribavirin (RBV) or interferon alpha (IFN-α) further increased the extent of viral inhibition. Ultrastructural electron microscopy studies revealed severe alterations of ZIKV-induced intracellular replication compartments upon infection of K22-treated cells. Importantly, the antiviral activity of K22 was demonstrated against several other members of the Flaviviridae family. It is tempting to speculate that K22 exerts its broad antiviral activity against several positive-strand RNA viruses via a similar mechanism and thereby represents an attractive candidate for development as a panviral inhibitor.",2018 Oct 24,"['García-Nicolás, Obdulio', ""V'kovski, Philip"", 'Vielle, Nathalie J.', 'Ebert, Nadine', 'Züst, Roland', 'Portmann, Jasmine', 'Stalder, Hanspeter', 'Gaschen, Véronique', 'Vieyres, Gabrielle', 'Stoffel, Michael', 'Schweizer, Matthias', 'Summerfield, Artur', 'Engler, Olivier', 'Pietschmann, Thomas', 'Todt, Daniel', 'Alves, Marco P.', 'Thiel, Volker', 'Pfaender, Stephanie']",Antimicrob Agents Chemother,,,False
710d63d02151ad5a6ed5eb93dd30d7a531445402,PMC,N-substituted phenylbenzamides of the niclosamide chemotype attenuate obesity related changes in high fat diet fed mice,http://dx.doi.org/10.1371/journal.pone.0204605,PMC6201879,30359371,CC BY,"Obesity and insulin resistance are primary risk factors for Non-Alcoholic Fatty Liver Disease (NAFLD). NAFLD is generally exhibited by non-progressive simple steatosis. However, a significant subset of patient’s progress to nonalcoholic steatohepatitis (NASH) that is defined by the presence of steatosis, inflammation and hepatocyte injury with fibrosis. Unfortunately, there are no approved therapies for NAFLD or NASH and therefore therapeutic approaches are urgently needed. Niclosamide is an U.S. Food and Drug Administration (FDA)-approved anthelmintic drug that mediates its effect by uncoupling oxidative phosphorylation. Niclosamide and its salt forms, Niclosamide Ethanolamine (NEN), and Niclosamide Piperazine (NPP) have shown efficacy in murine models of diet induced obesity characterized by attenuation of the prominent fatty liver disease phenotype and improved glucose metabolism. While the exact mechanism(s) underlying these changes remains unclear, the ability to uncouple oxidative phosphorylation leading to increased energy expenditure and lipid metabolism or attenuation of PKA mediated glucagon signaling in the liver have been proposed. Unfortunately, niclosamide has very poor water solubility, leading to low oral bioavailability. This, in addition to mitochondrial uncoupling activity and potential genotoxicity have reduced enthusiasm for its clinical use. More recently, salt forms of niclosamide, NEN and NPP, have demonstrated improved oral bioavailability while retaining activity. This suggests that development of safer more effective niclosamide derivatives for the treatment of NAFLD and Type 2 Diabetes may be possible. Herein we explored the ability of a series of N-substituted phenylbenzamide derivatives of the niclosamide salicylanilide chemotype to attenuate hepatic steatosis using a novel phenotypic in vitro model of fatty liver and the high fat diet-fed mouse model of diet induced obesity. These studies identified novel compounds with improved pre-clinical properties that attenuate hepatic steatosis in vitro and in vivo. These compounds with improved drug properties may be useful in alleviating symptoms and protection against disease progression in patients with metabolic syndrome and NAFLD.",2018 Oct 25,"['Bhagat, Hiral A.', 'Compton, Sarah A.', 'Musso, David L.', 'Laudeman, Christopher P.', 'Jackson, Kimberly M. P.', 'Yi, Na Young', 'Nierobisz, Lidia S.', 'Forsberg, Lawrence', 'Brenman, Jay E.', 'Sexton, Jonathan Z.']",PLoS One,,,True
8e08fc4e2bad1f9e32a4034e66d96014978e070f,PMC,Viral Respiratory Infections in the Neonatal Intensive Care Unit—A Review,http://dx.doi.org/10.3389/fmicb.2018.02484,PMC6202802,30405557,CC BY,"Although infrequent, respiratory viral infections (RVIs) during birth hospitalization have a significant impact on short- and long-term morbidity in term and preterm neonates. RVI have been associated with increased length of hospital stay, severe disease course, unnecessary antimicrobial exposure and nosocomial outbreaks in the neonatal intensive care unit (NICU). Virus transmission has been described to occur via health care professionals, parents and other visitors. Most at risk are infants born prematurely, due to their immature immune system and the fact that they stay in the NICU for a considerable length of time. A prevalence of RVIs in the NICU in symptomatic infants of 6–30% has been described, although RVIs are most probably underdiagnosed, since testing for viral pathogens is not performed routinely in symptomatic patients in many NICUs. Additional challenges are the wide range of clinical presentation of RVIs, their similarity to bacterial infections and the unreliable detection methods prior to the era of molecular biology based technologies. In this review, current knowledge of early-life RVI in the NICU is discussed. Reviewed viral pathogens include human rhinovirus, respiratory syncytial virus and influenza virus, and discussed literature is restricted to reports based on modern molecular biology techniques. The review highlights therapeutic approaches and possible preventive strategies. Furthermore, short- and long-term consequences of RVIs in infants hospitalized in the NICU are discussed.",2018 Oct 19,"['Pichler, Karin', 'Assadian, Ojan', 'Berger, Angelika']",Front Microbiol,,,True
9fd83230962e678e8ec4d5dffee0bb431e19c2d9,PMC,Metagenomic analysis of viral nucleic acid extraction methods in respiratory clinical samples,http://dx.doi.org/10.1186/s12864-018-5152-5,PMC6202819,30359242,CC BY,"BACKGROUND: Numerous protocols for viral enrichment and genome amplification have been created. However, the direct identification of viral genomes from clinical specimens using next-generation sequencing (NGS) still has its challenges. As a selected viral nucleic acid extraction method may determine the sensitivity and reliability of NGS, it is still valuable to evaluate the extraction efficiency of different extraction kits using clinical specimens directly. RESULTS: In this study, we performed qRT-PCR and viral metagenomic analysis of the extraction efficiency of four commonly used Qiagen extraction kits: QIAamp Viral RNA Mini Kit (VRMK), QIAamp MinElute Virus Spin Kit (MVSK), RNeasy Mini Kit (RMK), and RNeasy Plus Micro Kit (RPMK), using a mixed respiratory clinical sample without any pre-treatment. This sample contained an adenovirus (ADV), influenza virus A (Flu A), human parainfluenza virus 3 (PIV3), human coronavirus OC43 (OC43), and human metapneumovirus (HMPV). The quantity and quality of the viral extracts were significantly different among these kits. The highest threshold cycle(Ct)values for ADV and OC43 were obtained by using the RPMK. The MVSK had the lowest Ct values for ADV and PIV3. The RMK revealed the lowest detectability for HMPV and PIV3. The most effective rate of NGS data at 67.47% was observed with the RPMK. The other three kits ranged between 12.1–26.79% effectiveness rates for the NGS data. Most importantly, compared to the other three kits the highest proportion of non-host reads was obtained by the RPMK. The MVSK performed best with the lowest Ct value of 20.5 in the extraction of ADV, while the RMK revealed the best extraction efficiency by NGS analysis. CONCLUSIONS: The evaluation of viral nucleic acid extraction efficiency is different between NGS and qRT-PCR analysis. The RPMK was most applicable for the metagenomic analysis of viral RNA and enabled more sensitive identification of the RNA virus genome in respiratory clinical samples. In addition, viral RNA extraction kits were also applicable for metagenomic analysis of the DNA virus. Our results highlighted the importance of nucleic acid extraction kit selection, which has a major impact on the yield and number of viral reads by NGS analysis. Therefore, the choice of extraction method for a given viral pathogen needs to be carefully considered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-5152-5) contains supplementary material, which is available to authorized users.",2018 Oct 25,"['Zhang, Dan', 'Lou, Xiuyu', 'Yan, Hao', 'Pan, Junhang', 'Mao, Haiyan', 'Tang, Hongfeng', 'Shu, Yan', 'Zhao, Yun', 'Liu, Lei', 'Li, Junping', 'Chen, Jiang', 'Zhang, Yanjun', 'Ma, Xuejun']",BMC Genomics,,,True
042a57ce54d353b67f9faff39f7829c45dc7b101,PMC,HIGH-FLOW NASAL CANNULA POST-TRACHEAL EXTUBATION IN A CHILD WITH UPPER AIRWAY OBSTRUCTION: CASE REPORT,http://dx.doi.org/10.1590/1984-0462/;2018;36;3;00010,PMC6202903,29995143,CC BY,"OBJECTIVE: To report a case of a patient who required tracheal intubation in a pediatric emergency department due to acute laryngitis and that, after the planned extubation, has successfully used the high-flow nasal cannula, which possibly prevented extubation failure. CASE DESCRIPTION: A male 8-month-old child was admitted to the pediatric emergency room with acute respiratory distress due to a high airway obstruction secondary to severe acute laryngitis. He was immediately intubated and referred to the pediatric intensive care unit. He presented extubation failure due to a significant laryngeal edema evidenced by bronchoscopy. In the second attempt to extubate, he presented respiratory distress, but, after the use of the high-flow nasal cannula, he became stable, reducing the heart and respiratory frequencies, and the extubation was successful. COMMENTS: The use of the high-flow nasal cannula was effective and presented good response in this patient with acute laryngitis, suggesting that it is a possible adjuvant for the treatment, avoiding worsening respiratory conditions and the need for reintubation.",2018 Jul-Sep,"['Colleti, José', 'Longui, Tâmara Eleamen', 'de Carvalho, Werther Brunow']",Rev Paul Pediatr,,,True
8a973597ea07d63537723d0324a68fe3759b90ff,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,True
a7fa0fb652d9df8708a8fb3871c570a4b7c49fc2,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
5d67deff445ec26a1e0f225d8cccaeac29e8e0cd,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
f6dfe154603d36715fca0b0800a327c20602bb7d,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
a16177a121c8cd6dc0401fa9f55bef176014f889,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
0b25b6ac37a8372b302beaf07e4a762ac1280c92,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
17c9d67783ce4310a85579c92c740e84d37089f6,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
9a1e60406dc90e68ea00c7b63fcab4efb3377833,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
bbb61993136523b181f4d5c2b8b8649d3cd9c15f,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
79db746ee5d488c161f0b9f8bb067ecf083041b6,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
ab37817f815bf7955c665365194290c31562b30e,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
c8f255c7dc52b6b1fe70e16f28080de37702a94c,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
d692ce535ad2b2e604b55410dc3c99f4c4e5c25d,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
a7fa0fb652d9df8708a8fb3871c570a4b7c49fc2,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
8de4be67be5e538b4379f8fb29ded9d070bd51c8,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
e1cd4fbf10d3e3bcdafa5e925a3c9fc5ae65fe3a,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
559f1c4821058e29a2bc686dbd3be57ed5cf051e,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
800562497270a57d8318caef6ca1b2635f8bcf7c,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
a75d14bcd71fb73447c250ea3217cb1a52e7973c,PMC,A novel framework for inferring parameters of transmission from viral sequence data,http://dx.doi.org/10.1371/journal.pgen.1007718,PMC6203404,30325921,CC BY,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events, designed for influenza virus, but adaptable to other viral species. Our approach solves multiple shortcomings of previous methods for this purpose; for example, we consider transmission as an event involving whole viruses, rather than sets of independent alleles. We demonstrate how selection during transmission and noisy sequence data may each affect naive inferences of the population bottleneck, accounting for these in our framework so as to achieve a correct inference. We identify circumstances in which selection for increased viral transmission may or may not be identified from data. Applying our method to experimental data in which transmission occurs in the presence of strong selection, we show that our framework grants a more quantitative insight into transmission events than previous approaches, inferring the bottleneck in a manner that accounts for selection, both for within-host virulence, and for inherent viral transmissibility. Our work provides new opportunities for studying transmission processes in influenza, and by extension, in other infectious diseases.",2018 Oct 16,"['Lumby, Casper K.', 'Nene, Nuno R.', 'Illingworth, Christopher J. R.']",PLoS Genet,,,False
a9af3598d5bb039283b8334f770488e6e8e6821c,PMC,"Changes in mRNA abundance drive shuttling of RNA binding proteins, linking cytoplasmic RNA degradation to transcription",http://dx.doi.org/10.7554/eLife.37663,PMC6203436,30281021,CC BY,"Alterations in global mRNA decay broadly impact multiple stages of gene expression, although signals that connect these processes are incompletely defined. Here, we used tandem mass tag labeling coupled with mass spectrometry to reveal that changing the mRNA decay landscape, as frequently occurs during viral infection, results in subcellular redistribution of RNA binding proteins (RBPs) in human cells. Accelerating Xrn1-dependent mRNA decay through expression of a gammaherpesviral endonuclease drove nuclear translocation of many RBPs, including poly(A) tail-associated proteins. Conversely, cells lacking Xrn1 exhibited changes in the localization or abundance of numerous factors linked to mRNA turnover. Using these data, we uncovered a new role for relocalized cytoplasmic poly(A) binding protein in repressing recruitment of TATA binding protein and RNA polymerase II to promoters. Collectively, our results show that changes in cytoplasmic mRNA decay can directly impact protein localization, providing a mechanism to connect seemingly distal stages of gene expression.",,"['Gilbertson, Sarah', 'Federspiel, Joel D', 'Hartenian, Ella', 'Cristea, Ileana M', 'Glaunsinger, Britt']",eLife.; 7:e37663,,,True
c9ac0a1d2dd861bfa590dc654ddadb324a993fa0,PMC,"What happened to health service utilization, health care expenditures, and quality of care in patients with acute pancreatitis after implementation of global budgeting in Taiwan?",http://dx.doi.org/10.1097/MD.0000000000012620,PMC6203586,30313049,CC BY,"AIM: Acute pancreatitis is associated with significant morbidity and mortality. In the United States, more than 3,00,000 patients are admitted and about 20,000 die from acute pancreatitis per year. In Taiwan, the incidence rate of acute pancreatitis is 0.03% and the mortality rate among severe acute pancreatitis is 16.3%. The aim of the study was to evaluate the impact of the global budgeting system on health service utilization, health care expenditures, and quality of care among patients with acute pancreatitis in Taiwan. MATERIALS AND METHODS: The National Health Insurance Research Database (NHIRD) was used for analysis. Data on patients with acute pancreatitis diagnosed during the period 2000 and 2001 were used as baseline data, and data from 2004 and 2005 were used as post-intervention data. The length of stay (LOS), diagnostic costs, drug cost, therapy costs, total costs, risk of readmission within 14 days, and risk of revisiting the emergency department (ED) within 3 days of discharge before and after implementation of the global budgeting system were compared and analyzed. RESULTS: Data on 2810 patients with acute pancreatitis were analyzed in this study. There was a significant difference in mean LOS before and after introduction of the global budget system (7.34 ± 0.22 days and 7.82 ± 0.22 days, respectively; P < .001)). The mean total costs before and after implementation of the global budget system were Taiwan dollars (NT$) 28,290.66 ± 1576.32 and NT$ 42,341.83 ± 2285.23, respectively. The mean rate of revisiting the ED within 3 days decreased from 9.9 ± 0.9% before adoption of global budgeting to 7.2 ± 0.6% after implementation of the system. The mean 14-day re-admission rates before and after introduction of global budgeting were 11.6 ± 1.0% and 7.9 ± 0.7%, respectively. CONCLUSION: The global budget system was associated with significantly longer length of stay, higher health care expenditures, and better quality of care in patients treated for acute pancreatitis.",2018 Oct 12,"['Ko, Ya-Lin', 'Wang, Jyun-Wei', 'Hsu, Hui-Mei', 'Kao, Chia-Hung', 'Lin, Chun-Yi']",Medicine (Baltimore),,,True
6c99164301444faa6eacb7f37d4e00944fbd167b,PMC,"African perspectives: modern complexities of emerging, re-emerging, and endemic zoonoses",http://dx.doi.org/10.7189/johg.08.020310,PMC6204004,30410736,CC BY,,,"['Muzemil, Abdulazeez', 'Fasanmi, Olubunmi Gabriel', 'Fasina, Folorunso Oludayo']",J Glob Health.; 8(2):020310,,,True
e16483af81cf19dd5ffdf9dc74c26dc3c2f5478f,PMC,"Selection and validation of suitable reference genes for qPCR gene expression analysis in goats and sheep under Peste des petits ruminants virus (PPRV), lineage IV infection",http://dx.doi.org/10.1038/s41598-018-34236-7,PMC6206032,30374051,CC BY,"Identification of suitable candidate reference genes is an important prerequisite for validating the gene expression data obtained from downstream analysis of RNA sequencing using quantitative real time PCR (qRT-PCR). Though existence of a universal reference gene is myth, commonly used reference genes can be assessed for expression stability to confer their suitability to be used as candidate reference genes in gene expression studies. In this study, we evaluated the expression stability of ten most commonly used reference genes (GAPDH, ACTB, HSP90, HMBS, 18S rRNA, B2M, POLR2A, HPRT1, ACAC, YWHAZ) in fourteen different Peste des petits ruminants virus (PPRV) infected tissues of goats and sheep. RefFinder and RankAggreg software were used to deduce comprehensive ranking of reference genes. Our results suggested HMBS and B2M in goats and HMBS and HPRT1 in sheep can be used as suitable endogenous controls in gene expression studies of PPRV infection irrespective of tissues and condition as a whole, thus eliminating the use of tissue specific/ condition specific endogenous controls. We report for the first time suitable reference genes for gene expression studies in PPRV infected tissues. The reference genes determined here can be useful for future studies on gene expression in sheep and goat infected with PPRV, thus saving extra efforts and time of repeating the reference gene determination and validation.",2018 Oct 29,"['Sahu, Amit Ranjan', 'Wani, Sajad Ahmad', 'Saxena, Shikha', 'Rajak, Kaushal Kishor', 'Chaudhary, Dheeraj', 'Sahoo, Aditya Prasad', 'Khanduri, Alok', 'Pandey, Aruna', 'Mondal, Piyali', 'Malla, Waseem Akram', 'Khan, Raja Ishaq Nabi', 'Tiwari, Ashok Kumar', 'Mishra, Bina', 'Muthuchelvan, D.', 'Mishra, Bishnu Prasad', 'Singh, Raj Kumar', 'Gandham, Ravi Kumar']",Sci Rep,,,False
d4090dff0fba51422afb6bf34f29c10f9a35caac,PMC,"Selection and validation of suitable reference genes for qPCR gene expression analysis in goats and sheep under Peste des petits ruminants virus (PPRV), lineage IV infection",http://dx.doi.org/10.1038/s41598-018-34236-7,PMC6206032,30374051,CC BY,"Identification of suitable candidate reference genes is an important prerequisite for validating the gene expression data obtained from downstream analysis of RNA sequencing using quantitative real time PCR (qRT-PCR). Though existence of a universal reference gene is myth, commonly used reference genes can be assessed for expression stability to confer their suitability to be used as candidate reference genes in gene expression studies. In this study, we evaluated the expression stability of ten most commonly used reference genes (GAPDH, ACTB, HSP90, HMBS, 18S rRNA, B2M, POLR2A, HPRT1, ACAC, YWHAZ) in fourteen different Peste des petits ruminants virus (PPRV) infected tissues of goats and sheep. RefFinder and RankAggreg software were used to deduce comprehensive ranking of reference genes. Our results suggested HMBS and B2M in goats and HMBS and HPRT1 in sheep can be used as suitable endogenous controls in gene expression studies of PPRV infection irrespective of tissues and condition as a whole, thus eliminating the use of tissue specific/ condition specific endogenous controls. We report for the first time suitable reference genes for gene expression studies in PPRV infected tissues. The reference genes determined here can be useful for future studies on gene expression in sheep and goat infected with PPRV, thus saving extra efforts and time of repeating the reference gene determination and validation.",2018 Oct 29,"['Sahu, Amit Ranjan', 'Wani, Sajad Ahmad', 'Saxena, Shikha', 'Rajak, Kaushal Kishor', 'Chaudhary, Dheeraj', 'Sahoo, Aditya Prasad', 'Khanduri, Alok', 'Pandey, Aruna', 'Mondal, Piyali', 'Malla, Waseem Akram', 'Khan, Raja Ishaq Nabi', 'Tiwari, Ashok Kumar', 'Mishra, Bina', 'Muthuchelvan, D.', 'Mishra, Bishnu Prasad', 'Singh, Raj Kumar', 'Gandham, Ravi Kumar']",Sci Rep,,,True
95648e7d8513a790e6e07df43a7ffac9bf882db5,PMC,Burden and Risk Factors for Coronavirus Infections in Infants in Rural Nepal,http://dx.doi.org/10.1093/cid/ciy317,PMC6206108,29668900,CC BY,"BACKGROUND: Knowledge of risk factors for symptomatic human coronavirus (HCoV) infections in children in community settings is limited. We estimated the disease burden and impact of birth-related, maternal, household, and seasonal factors on HCoV infections among children from birth to 6 months old in rural Nepal. METHODS: Prospective, active, weekly surveillance for acute respiratory infections (ARIs) was conducted in infants over a period of 3 years during 2 consecutive, population-based randomized trials of maternal influenza immunization. Midnasal swabs were collected for acute respiratory symptoms and tested for HCoV and other viruses by reverse-transcription polymerase chain reaction. Association between HCoV incidence and potential risk factors was modeled using Poisson regression. RESULTS: Overall, 282 of 3505 (8%) infants experienced an HCoV ARI within the first 6 months of life. HCoV incidence overall was 255.6 (95% confidence interval [CI], 227.3–286.5) per 1000 person-years, and was more than twice as high among nonneonates than among neonates (incidence rate ratio [IRR], 2.53; 95% CI, 1.52–4.21). HCoV ARI incidence was also positively associated with the number of children <5 years of age per room in a household (IRR, 1.13; 95% CI, 1.01–1.28). Of the 296 HCoV infections detected, 46% were coinfections with other respiratory viruses. While HCoVs were detected throughout the study period, seasonal variation was also observed, with incidence peaking in 2 winters (December–February) and 1 autumn (September–November). CONCLUSIONS: HCoV is associated with a substantial proportion of illnesses among young infants in rural Nepal. There is an increased risk of HCoV infection beyond the first month of life.",2018 Nov 15,"['Uddin, S M Iftekhar', 'Englund, Janet A', 'Kuypers, Jane Y', 'Chu, Helen Y', 'Steinhoff, Mark C', 'Khatry, Subarna K', 'LeClerq, Steve C', 'Tielsch, James M', 'Mullany, Luke C', 'Shrestha, Laxman', 'Katz, Joanne']",Clin Infect Dis,,,True
356381d431c775e013710e6bff7ab89a507eb013,PMC,Continuous Invasion by Respiratory Viruses Observed in Rural Households During a Respiratory Syncytial Virus Seasonal Outbreak in Coastal Kenya,http://dx.doi.org/10.1093/cid/ciy313,PMC6206121,29668861,CC BY,"BACKGROUND: Households are high-intensity close-contact environments favorable for transmission of respiratory viruses, yet little is known for low-income settings. METHODS: Active surveillance was completed on 47 households in rural coastal Kenya over 6 months during a respiratory syncytial virus (RSV) season. Nasopharyngeal swabs (NPSs) were taken from 483 household members twice weekly irrespective of symptoms. Using molecular diagnostics, NPSs from 6 households were screened for 15 respiratory viruses and the remainder of households only for the most frequent viruses observed: rhinovirus (RV), human coronavirus (HCoV; comprising strains 229E, OC43, and NL63), adenovirus (AdV), and RSV (A and B). RESULTS: Of 16928 NPSs tested for the common viruses, 4259 (25.2%) were positive for ≥1 target; 596 (13.8%) had coinfections. Detection frequencies were 10.5% RV (1780), 7.5% HCoV (1274), 7.3% AdV (1232), and 3.2% RSV (537). On average, each household and individual had 6 and 3 different viruses detected over the study period, respectively. Rhinovirus and HCoV were detected in all the 47 households while AdV and RSV were detected in 45 (95.7%) and 40 (85.1%) households, respectively. The individual risk of infection over the 6-month period was 93.4%, 80.1%, 71.6%, 61.5%, and 37.1% for any virus, RV, HCoV, AdV, and RSV, respectively. NPSs collected during symptomatic days and from younger age groups had higher prevalence of virus detection relative to respective counterparts. RSV was underrepresented in households relative to hospital admission data. CONCLUSIONS: In this household setting, respiratory virus infections and associated illness are ubiquitous. Future studies should address the health and economic implications of these observations.",2018 Nov 15,"['Munywoki, Patrick K', 'Koech, Dorothy C', 'Agoti, Charles N', 'Cane, Patricia A', 'Medley, Graham F', 'Nokes, D James']",Clin Infect Dis,,,True
001b3d68eb9da2d0fbae9e526d07ab96afe3f312,PMC,"Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform",http://dx.doi.org/10.1038/s42003-018-0175-7,PMC6206136,30393776,CC BY,"Emerging and re-emerging zoonotic viral diseases are major threats to global health, economic stability, and national security. Vaccines are key for reducing coronaviral disease burden; however, the utility of live-attenuated vaccines is limited by risks of reversion or repair. Because of their history of emergence events due to their prevalence in zoonotic pools, designing live-attenuated coronavirus vaccines that can be rapidly and broadly implemented is essential for outbreak preparedness. Here, we show that coronaviruses with completely rewired transcription regulatory networks (TRNs) are effective vaccines against SARS-CoV. The TRN-rewired viruses are attenuated and protect against lethal SARS-CoV challenge. While a 3-nt rewired TRN reverts via second-site mutation upon serial passage, a 7-nt rewired TRN is more stable, suggesting that a more extensively rewired TRN might be essential for avoiding growth selection. In summary, rewiring the TRN is a feasible strategy for limiting reversion in an effective live-attenuated coronavirus vaccine candidate that is potentially portable across the Nidovirales order.",2018 Oct 29,"['Graham, Rachel L.', 'Deming, Damon J.', 'Deming, Meagan E.', 'Yount, Boyd L.', 'Baric, Ralph S.']",Commun Biol,,,False
dadb8cce14cbf09b6fbaf927b0b2524899ac028d,PMC,"Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform",http://dx.doi.org/10.1038/s42003-018-0175-7,PMC6206136,30393776,CC BY,"Emerging and re-emerging zoonotic viral diseases are major threats to global health, economic stability, and national security. Vaccines are key for reducing coronaviral disease burden; however, the utility of live-attenuated vaccines is limited by risks of reversion or repair. Because of their history of emergence events due to their prevalence in zoonotic pools, designing live-attenuated coronavirus vaccines that can be rapidly and broadly implemented is essential for outbreak preparedness. Here, we show that coronaviruses with completely rewired transcription regulatory networks (TRNs) are effective vaccines against SARS-CoV. The TRN-rewired viruses are attenuated and protect against lethal SARS-CoV challenge. While a 3-nt rewired TRN reverts via second-site mutation upon serial passage, a 7-nt rewired TRN is more stable, suggesting that a more extensively rewired TRN might be essential for avoiding growth selection. In summary, rewiring the TRN is a feasible strategy for limiting reversion in an effective live-attenuated coronavirus vaccine candidate that is potentially portable across the Nidovirales order.",2018 Oct 29,"['Graham, Rachel L.', 'Deming, Damon J.', 'Deming, Meagan E.', 'Yount, Boyd L.', 'Baric, Ralph S.']",Commun Biol,,,True
2e7a5d9a03e6fdbce778e489686a2533d47f7463,PMC,Recent advances in understanding Crimean–Congo hemorrhagic fever virus,http://dx.doi.org/10.12688/f1000research.16189.1,PMC6206615,30416710,CC BY,"Crimean-Congo hemorrhagic fever virus (CCHFV) is a widely distributed hemorrhagic fever virus and the cause of hemorrhagic disease in Africa, Southern and Eastern Europe, the Middle East, India and Asia. Recent emergence of CCHFV into Spain indicates that the geographic range of this virus is expanding and the presence of its tick vector in several countries without reported disease suggest that CCHFV will continue to spread. Research into CCHFV was historically limited by a lack of suitable animal models and tools to study viral pathogenesis. However, in the past few years the toolset for studying CCHFV has expanded with small animal and non-human primate models for CCHFV being developed along with a reverse genetics system that allows for investigation of viral determinants of disease. These tools have been utilized to understand how CCHFV antagonizes host restriction factors and to develop novel vaccine candidates that may help limit the substantial morbidity and mortality in humans caused by CCHFV.",2018 Oct 29,"['Hawman, David W.', 'Feldmann, Heinz']",F1000Res,,,True
60758e874c80de9dcab280027279347b055b945a,PMC,Quality control implementation for universal characterization of DNA and RNA viruses in clinical respiratory samples using single metagenomic next-generation sequencing workflow,http://dx.doi.org/10.1186/s12879-018-3446-5,PMC6206636,30373528,CC BY,"BACKGROUND: In recent years, metagenomic Next-Generation Sequencing (mNGS) has increasingly been used for an accurate assumption-free virological diagnosis. However, the systematic workflow evaluation on clinical respiratory samples and implementation of quality controls (QCs) is still lacking. METHODS: A total of 3 QCs were implemented and processed through the whole mNGS workflow: a no-template-control to evaluate contamination issues during the process; an internal and an external QC to check the integrity of the reagents, equipment, the presence of inhibitors, and to allow the validation of results for each sample. The workflow was then evaluated on 37 clinical respiratory samples from patients with acute respiratory infections previously tested for a broad panel of viruses using semi-quantitative real-time PCR assays (28 positive samples including 6 multiple viral infections; 9 negative samples). Selected specimens included nasopharyngeal swabs (n = 20), aspirates (n = 10), or sputums (n = 7). RESULTS: The optimal spiking level of the internal QC was first determined in order to be sufficiently detected without overconsumption of sequencing reads. According to QC validation criteria, mNGS results were validated for 34/37 selected samples. For valid samples, viral genotypes were accurately determined for 36/36 viruses detected with PCR (viral genome coverage ranged from 0.6 to 100%, median = 67.7%). This mNGS workflow allowed the detection of DNA and RNA viruses up to a semi-quantitative PCR Ct value of 36. The six multiple viral infections involving 2 to 4 viruses were also fully characterized. A strong correlation between results of mNGS and real-time PCR was obtained for each type of viral genome (R(2) ranged from 0.72 for linear single-stranded (ss) RNA viruses to 0.98 for linear ssDNA viruses). CONCLUSIONS: Although the potential of mNGS technology is very promising, further evaluation studies are urgently needed for its routine clinical use within a reasonable timeframe. The approach described herein is crucial to bring standardization and to ensure the quality of the generated sequences in clinical setting. We provide an easy-to-use single protocol successfully evaluated for the characterization of a broad and representative panel of DNA and RNA respiratory viruses in various types of clinical samples. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3446-5) contains supplementary material, which is available to authorized users.",2018 Oct 29,"['Bal, A.', 'Pichon, M.', 'Picard, C.', 'Casalegno, J. S.', 'Valette, M.', 'Schuffenecker, I.', 'Billard, L.', 'Vallet, S.', 'Vilchez, G.', 'Cheynet, V.', 'Oriol, G.', 'Trouillet-Assant, S.', 'Gillet, Y.', 'Lina, B.', 'Brengel-Pesce, K.', 'Morfin, F.', 'Josset, L.']",BMC Infect Dis,,,True
14cacbe5b5cbaa60f79ce5249505a60180838885,PMC,Fomite-mediated transmission as a sufficient pathway: a comparative analysis across three viral pathogens,http://dx.doi.org/10.1186/s12879-018-3425-x,PMC6206643,30373527,CC BY,"BACKGROUND: Fomite mediated transmission can be an important pathway causing significant disease transmission in number of settings such as schools, daycare centers, and long-term care facilities. The importance of these pathways relative to other transmission pathways such as direct person-person or airborne will depend on the characteristics of the particular pathogen and the venue in which transmission occurs. Here we analyze fomite mediated transmission through a comparative analysis across multiple pathogens and venues. METHODS: We developed and analyzed a compartmental model that explicitly accounts for fomite transmission by including pathogen transfer between hands and surfaces. We consider two sub-types of fomite-mediated transmission: direct fomite (e.g., shedding onto fomites) and hand-fomite (e.g., shedding onto hands and then contacting fomites). We use this model to examine three pathogens with distinct environmental characteristics (influenza, rhinovirus, and norovirus) in four venue types. To parameterize the model for each pathogen we conducted a thorough literature search. RESULTS: Based on parameter estimates from the literature the reproductive number ([Formula: see text] ) for the fomite route for rhinovirus and norovirus is greater than 1 in nearly all venues considered, suggesting that this route can sustain transmission. For influenza, on the other hand, [Formula: see text] for the fomite route is smaller suggesting many conditions in which the pathway may not sustain transmission. Additionally, the direct fomite route is more relevant than the hand-fomite route for influenza and rhinovirus, compared to norovirus. The relative importance of the hand-fomite vs. direct fomite route for norovirus is strongly dependent on the fraction of pathogens initially shed to hands. Sensitivity analysis stresses the need for accurate measurements of environmental inactivation rates, transfer efficiencies, and pathogen shedding. CONCLUSIONS: Fomite-mediated transmission is an important pathway for the three pathogens examined. The effectiveness of environmental interventions differs significantly both by pathogen and venue. While fomite-based interventions may be able to lower [Formula: see text] for fomites below 1 and interrupt transmission, rhinovirus and norovirus are so infectious ([Formula: see text] ) that single environmental interventions are unlikely to interrupt fomite transmission for these pathogens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3425-x) contains supplementary material, which is available to authorized users.",2018 Oct 29,"['Kraay, Alicia N.M.', 'Hayashi, Michael A.L.', 'Hernandez-Ceron, Nancy', 'Spicknall, Ian H.', 'Eisenberg, Marisa C.', 'Meza, Rafael', 'Eisenberg, Joseph N.S.']",BMC Infect Dis,,,False
239f4596308a1247bf27a034c3cab95e0771215f,PMC,Fomite-mediated transmission as a sufficient pathway: a comparative analysis across three viral pathogens,http://dx.doi.org/10.1186/s12879-018-3425-x,PMC6206643,30373527,CC BY,"BACKGROUND: Fomite mediated transmission can be an important pathway causing significant disease transmission in number of settings such as schools, daycare centers, and long-term care facilities. The importance of these pathways relative to other transmission pathways such as direct person-person or airborne will depend on the characteristics of the particular pathogen and the venue in which transmission occurs. Here we analyze fomite mediated transmission through a comparative analysis across multiple pathogens and venues. METHODS: We developed and analyzed a compartmental model that explicitly accounts for fomite transmission by including pathogen transfer between hands and surfaces. We consider two sub-types of fomite-mediated transmission: direct fomite (e.g., shedding onto fomites) and hand-fomite (e.g., shedding onto hands and then contacting fomites). We use this model to examine three pathogens with distinct environmental characteristics (influenza, rhinovirus, and norovirus) in four venue types. To parameterize the model for each pathogen we conducted a thorough literature search. RESULTS: Based on parameter estimates from the literature the reproductive number ([Formula: see text] ) for the fomite route for rhinovirus and norovirus is greater than 1 in nearly all venues considered, suggesting that this route can sustain transmission. For influenza, on the other hand, [Formula: see text] for the fomite route is smaller suggesting many conditions in which the pathway may not sustain transmission. Additionally, the direct fomite route is more relevant than the hand-fomite route for influenza and rhinovirus, compared to norovirus. The relative importance of the hand-fomite vs. direct fomite route for norovirus is strongly dependent on the fraction of pathogens initially shed to hands. Sensitivity analysis stresses the need for accurate measurements of environmental inactivation rates, transfer efficiencies, and pathogen shedding. CONCLUSIONS: Fomite-mediated transmission is an important pathway for the three pathogens examined. The effectiveness of environmental interventions differs significantly both by pathogen and venue. While fomite-based interventions may be able to lower [Formula: see text] for fomites below 1 and interrupt transmission, rhinovirus and norovirus are so infectious ([Formula: see text] ) that single environmental interventions are unlikely to interrupt fomite transmission for these pathogens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3425-x) contains supplementary material, which is available to authorized users.",2018 Oct 29,"['Kraay, Alicia N.M.', 'Hayashi, Michael A.L.', 'Hernandez-Ceron, Nancy', 'Spicknall, Ian H.', 'Eisenberg, Marisa C.', 'Meza, Rafael', 'Eisenberg, Joseph N.S.']",BMC Infect Dis,,,True
806a1df203eb5126eec25561bd4cb1b10df18c53,PMC,An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides,http://dx.doi.org/10.1371/journal.ppat.1007368,PMC6207329,30335851,CC BY,"Infection with human BK polyomavirus, a small double-stranded DNA virus, potentially results in severe complications in immunocompromised patients. Here, we describe the in vivo variability and evolution of the BK polyomavirus by deep sequencing. Our data reveal the highest genomic evolutionary rate described in double-stranded DNA viruses, i.e., 10(−3)–10(−5) substitutions per nucleotide site per year. High mutation rates in viruses allow their escape from immune surveillance and adaptation to new hosts. By combining mutational landscapes across viral genomes with in silico prediction of viral peptides, we demonstrate the presence of significantly more coding substitutions within predicted cognate HLA-C-bound viral peptides than outside. This finding suggests a role for HLA-C in antiviral immunity, perhaps through the action of killer cell immunoglobulin-like receptors. The present study provides a comprehensive view of viral evolution and immune escape in a DNA virus.",2018 Oct 18,"['Domingo-Calap, Pilar', 'Schubert, Benjamin', 'Joly, Mélanie', 'Solis, Morgane', 'Untrau, Meiggie', 'Carapito, Raphael', 'Georgel, Philippe', 'Caillard, Sophie', 'Fafi-Kremer, Samira', 'Paul, Nicodème', 'Kohlbacher, Oliver', 'González-Candelas, Fernando', 'Bahram, Seiamak']",PLoS Pathog,,,True
71d83e9e51a491ff3494c4eac116d728abf99e34,PMC,An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides,http://dx.doi.org/10.1371/journal.ppat.1007368,PMC6207329,30335851,CC BY,"Infection with human BK polyomavirus, a small double-stranded DNA virus, potentially results in severe complications in immunocompromised patients. Here, we describe the in vivo variability and evolution of the BK polyomavirus by deep sequencing. Our data reveal the highest genomic evolutionary rate described in double-stranded DNA viruses, i.e., 10(−3)–10(−5) substitutions per nucleotide site per year. High mutation rates in viruses allow their escape from immune surveillance and adaptation to new hosts. By combining mutational landscapes across viral genomes with in silico prediction of viral peptides, we demonstrate the presence of significantly more coding substitutions within predicted cognate HLA-C-bound viral peptides than outside. This finding suggests a role for HLA-C in antiviral immunity, perhaps through the action of killer cell immunoglobulin-like receptors. The present study provides a comprehensive view of viral evolution and immune escape in a DNA virus.",2018 Oct 18,"['Domingo-Calap, Pilar', 'Schubert, Benjamin', 'Joly, Mélanie', 'Solis, Morgane', 'Untrau, Meiggie', 'Carapito, Raphael', 'Georgel, Philippe', 'Caillard, Sophie', 'Fafi-Kremer, Samira', 'Paul, Nicodème', 'Kohlbacher, Oliver', 'González-Candelas, Fernando', 'Bahram, Seiamak']",PLoS Pathog,,,False
7983367121b98cbe7927180b831af8ca15371dd6,PMC,An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides,http://dx.doi.org/10.1371/journal.ppat.1007368,PMC6207329,30335851,CC BY,"Infection with human BK polyomavirus, a small double-stranded DNA virus, potentially results in severe complications in immunocompromised patients. Here, we describe the in vivo variability and evolution of the BK polyomavirus by deep sequencing. Our data reveal the highest genomic evolutionary rate described in double-stranded DNA viruses, i.e., 10(−3)–10(−5) substitutions per nucleotide site per year. High mutation rates in viruses allow their escape from immune surveillance and adaptation to new hosts. By combining mutational landscapes across viral genomes with in silico prediction of viral peptides, we demonstrate the presence of significantly more coding substitutions within predicted cognate HLA-C-bound viral peptides than outside. This finding suggests a role for HLA-C in antiviral immunity, perhaps through the action of killer cell immunoglobulin-like receptors. The present study provides a comprehensive view of viral evolution and immune escape in a DNA virus.",2018 Oct 18,"['Domingo-Calap, Pilar', 'Schubert, Benjamin', 'Joly, Mélanie', 'Solis, Morgane', 'Untrau, Meiggie', 'Carapito, Raphael', 'Georgel, Philippe', 'Caillard, Sophie', 'Fafi-Kremer, Samira', 'Paul, Nicodème', 'Kohlbacher, Oliver', 'González-Candelas, Fernando', 'Bahram, Seiamak']",PLoS Pathog,,,False
92893fa52e72d2604a61e3676bd80420af8c4752,PMC,An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides,http://dx.doi.org/10.1371/journal.ppat.1007368,PMC6207329,30335851,CC BY,"Infection with human BK polyomavirus, a small double-stranded DNA virus, potentially results in severe complications in immunocompromised patients. Here, we describe the in vivo variability and evolution of the BK polyomavirus by deep sequencing. Our data reveal the highest genomic evolutionary rate described in double-stranded DNA viruses, i.e., 10(−3)–10(−5) substitutions per nucleotide site per year. High mutation rates in viruses allow their escape from immune surveillance and adaptation to new hosts. By combining mutational landscapes across viral genomes with in silico prediction of viral peptides, we demonstrate the presence of significantly more coding substitutions within predicted cognate HLA-C-bound viral peptides than outside. This finding suggests a role for HLA-C in antiviral immunity, perhaps through the action of killer cell immunoglobulin-like receptors. The present study provides a comprehensive view of viral evolution and immune escape in a DNA virus.",2018 Oct 18,"['Domingo-Calap, Pilar', 'Schubert, Benjamin', 'Joly, Mélanie', 'Solis, Morgane', 'Untrau, Meiggie', 'Carapito, Raphael', 'Georgel, Philippe', 'Caillard, Sophie', 'Fafi-Kremer, Samira', 'Paul, Nicodème', 'Kohlbacher, Oliver', 'González-Candelas, Fernando', 'Bahram, Seiamak']",PLoS Pathog,,,False
7ca9715531ac38b4f6daff82f746c09b1eabd67f,PMC,An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides,http://dx.doi.org/10.1371/journal.ppat.1007368,PMC6207329,30335851,CC BY,"Infection with human BK polyomavirus, a small double-stranded DNA virus, potentially results in severe complications in immunocompromised patients. Here, we describe the in vivo variability and evolution of the BK polyomavirus by deep sequencing. Our data reveal the highest genomic evolutionary rate described in double-stranded DNA viruses, i.e., 10(−3)–10(−5) substitutions per nucleotide site per year. High mutation rates in viruses allow their escape from immune surveillance and adaptation to new hosts. By combining mutational landscapes across viral genomes with in silico prediction of viral peptides, we demonstrate the presence of significantly more coding substitutions within predicted cognate HLA-C-bound viral peptides than outside. This finding suggests a role for HLA-C in antiviral immunity, perhaps through the action of killer cell immunoglobulin-like receptors. The present study provides a comprehensive view of viral evolution and immune escape in a DNA virus.",2018 Oct 18,"['Domingo-Calap, Pilar', 'Schubert, Benjamin', 'Joly, Mélanie', 'Solis, Morgane', 'Untrau, Meiggie', 'Carapito, Raphael', 'Georgel, Philippe', 'Caillard, Sophie', 'Fafi-Kremer, Samira', 'Paul, Nicodème', 'Kohlbacher, Oliver', 'González-Candelas, Fernando', 'Bahram, Seiamak']",PLoS Pathog,,,False
d8f3c91f1e82e0d720a91139af4ea94dfd3f5df5,PMC,An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides,http://dx.doi.org/10.1371/journal.ppat.1007368,PMC6207329,30335851,CC BY,"Infection with human BK polyomavirus, a small double-stranded DNA virus, potentially results in severe complications in immunocompromised patients. Here, we describe the in vivo variability and evolution of the BK polyomavirus by deep sequencing. Our data reveal the highest genomic evolutionary rate described in double-stranded DNA viruses, i.e., 10(−3)–10(−5) substitutions per nucleotide site per year. High mutation rates in viruses allow their escape from immune surveillance and adaptation to new hosts. By combining mutational landscapes across viral genomes with in silico prediction of viral peptides, we demonstrate the presence of significantly more coding substitutions within predicted cognate HLA-C-bound viral peptides than outside. This finding suggests a role for HLA-C in antiviral immunity, perhaps through the action of killer cell immunoglobulin-like receptors. The present study provides a comprehensive view of viral evolution and immune escape in a DNA virus.",2018 Oct 18,"['Domingo-Calap, Pilar', 'Schubert, Benjamin', 'Joly, Mélanie', 'Solis, Morgane', 'Untrau, Meiggie', 'Carapito, Raphael', 'Georgel, Philippe', 'Caillard, Sophie', 'Fafi-Kremer, Samira', 'Paul, Nicodème', 'Kohlbacher, Oliver', 'González-Candelas, Fernando', 'Bahram, Seiamak']",PLoS Pathog,,,False
17fd57932f302768e68f2a562ba63bc02b5697cd,PMC,An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides,http://dx.doi.org/10.1371/journal.ppat.1007368,PMC6207329,30335851,CC BY,"Infection with human BK polyomavirus, a small double-stranded DNA virus, potentially results in severe complications in immunocompromised patients. Here, we describe the in vivo variability and evolution of the BK polyomavirus by deep sequencing. Our data reveal the highest genomic evolutionary rate described in double-stranded DNA viruses, i.e., 10(−3)–10(−5) substitutions per nucleotide site per year. High mutation rates in viruses allow their escape from immune surveillance and adaptation to new hosts. By combining mutational landscapes across viral genomes with in silico prediction of viral peptides, we demonstrate the presence of significantly more coding substitutions within predicted cognate HLA-C-bound viral peptides than outside. This finding suggests a role for HLA-C in antiviral immunity, perhaps through the action of killer cell immunoglobulin-like receptors. The present study provides a comprehensive view of viral evolution and immune escape in a DNA virus.",2018 Oct 18,"['Domingo-Calap, Pilar', 'Schubert, Benjamin', 'Joly, Mélanie', 'Solis, Morgane', 'Untrau, Meiggie', 'Carapito, Raphael', 'Georgel, Philippe', 'Caillard, Sophie', 'Fafi-Kremer, Samira', 'Paul, Nicodème', 'Kohlbacher, Oliver', 'González-Candelas, Fernando', 'Bahram, Seiamak']",PLoS Pathog,,,False
c1dc7422f1716cf0750c974a86d1c5ac0b48d810,PMC,Discovery of Diverse Rodent and Bat Pestiviruses With Distinct Genomic and Phylogenetic Characteristics in Several Chinese Provinces,http://dx.doi.org/10.3389/fmicb.2018.02562,PMC6207626,30405596,CC BY,"Bats and rodents are widely distributed worldwide and can be native or intermediate reservoirs of many important zoonotic viruses. Pestiviruses are a group of virus species of the genus Pestivirus under the family Flaviviridae that can infect a wide variety of artiodactylous hosts, including swine and ruminants. Two classic types of pestiviruses, bovine viral diarrhea virus and classical swine fever virus, are important causative agents of mild-to-severe disease in bovine and swine hosts, respectively, and cause tremendous economic losses in these industries. Recent reports revealed that bats and rodents could also act as natural hosts of pestiviruses and an atypical porcine pestivirus, which cause disease in piglets, showed a close genetic relationship with a specific bat pestivirus, RaPestV-1. This study aimed to describe the detection and characterization of novel pestiviruses from bats and rodents in different locations by analyzing the available bat and rodent virome data from throughout China. Two bat pestivirus species and four rodent pestivirus species that are distinct from other known viruses were identified and sequenced. These viruses were identified from two bat species and four rodent species in different Chinese provinces. There were two distinct lineages present in these viruses, that differ from artiodactylous pestivirus. These findings expand our understanding of the genetic diversity of pestiviruses in bats and rodents and suggest the presence of a diverse set of pestiviruses in non-artiodactylous hosts. This study may provide new insight for the prevention of future viral disease outbreaks originating from bats and rodents.",2018 Oct 24,"['Wu, Zhiqiang', 'Liu, Bo', 'Du, Jiang', 'Zhang, Junpeng', 'Lu, Liang', 'Zhu, Guangjian', 'Han, Yelin', 'Su, Haoxiang', 'Yang, Li', 'Zhang, Shuyi', 'Liu, Qiyong', 'Jin, Qi']",Front Microbiol,,,True
6aaa4563100d784e74766eac29f4b2718ad7d256,PMC,A novel human coronavirus OC43 genotype detected in mainland China,http://dx.doi.org/10.1038/s41426-018-0171-5,PMC6207742,30377292,CC BY,,2018 Oct 30,"['Zhu, Yun', 'Li, Changchong', 'Chen, Li', 'Xu, Baoping', 'Zhou, Yunlian', 'Cao, Ling', 'Shang, Yunxiao', 'Fu, Zhou', 'Chen, Aihuan', 'Deng, Li', 'Bao, Yixiao', 'Sun, Yun', 'Ning, Limin', 'Liu, Chunyan', 'Yin, Ju', 'Xie, Zhengde', 'Shen, Kunling']",Emerg Microbes Infect,,,True
49af320db4eb8944ad055eff7bbd30d0dd3094b7,PMC,"A multiplex one-tube nested real time RT-PCR assay for simultaneous detection of respiratory syncytial virus, human rhinovirus and human metapneumovirus",http://dx.doi.org/10.1186/s12985-018-1061-0,PMC6208169,30376870,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV), human Rhinovirus (HRV) and human Metapneumo Virus (HMPV) are important viral pathogens causing acute respiratory tract infections in the hospitalized patients. Sensitive and accurate detection of RSV, HRV and HMPV is necessary for clinical diagnosis and treatment. RESULTS: A locked nucleic acid (LNA)-based multiplex closed one-tube nested real-time RT-PCR (mOTNRT-PCR) assay was developed for simultaneous detection of RSV, HRV and HMPV. The sensitivity, specificity, reproducibility and clinical performance of mOTNRT-PCR were evaluated and compared with individual real time PCR (RT-qPCR) assay using clinical samples. The analytical sensitivity of mOTNRT-PCR assay was 5 copies/reaction for RSV, HRV and HMPV, respectively, and no cross-reaction with other common respiratory viruses was observed. The coefficients of variation (CV) of intra-assay and inter-assay were between 0.51 to 3.67%. Of 398 nasopharyngeal aspirates samples tested, 109 (27.39%), 150 (37.69%) and 44 (11.06%) were positive for RSV, HRV and HMPV, respectively, whereas 95 (23.87%), 137 (34.42%) and 38 (9.55%) were positive for RSV, HRV and HMPV, respectively, by individual RT-qPCR assay. Thirty three samples that were positive by mOTNRT-PCR but negative by RT-qPCR were confirmed as true positives by sequencing using reported traditional two-step nested PCR assay. CONCLUSION: mOTNRT-PCR assay reveals extremely higher sensitivity than that of RT-qPCR assay for detecting RSV, HRV and HMPV in clinical settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1061-0) contains supplementary material, which is available to authorized users.",2018 Oct 30,"['Feng, Zhi-shan', 'Zhao, Li', 'Wang, Ji', 'Qiu, Fang-zhou', 'Zhao, Meng-chuan', 'Wang, Le', 'Duan, Su-xia', 'Zhang, Rui-qing', 'Chen, Chen', 'Qi, Ju-Ju', 'Fan, Tao', 'Li, Gui-xia', 'Ma, Xue-jun']",Virol J,,,True
0f91a79b8aec80b0320b6de47b30c38b3fc4a170,PMC,Changes in temperature alter the potential outcomes of virus host shifts,http://dx.doi.org/10.1371/journal.ppat.1007185,PMC6209381,30339695,CC BY,"Host shifts–where a pathogen jumps between different host species–are an important source of emerging infectious disease. With on-going climate change there is an increasing need to understand the effect changes in temperature may have on emerging infectious disease. We investigated whether species’ susceptibilities change with temperature and ask if susceptibility is greatest at different temperatures in different species. We infected 45 species of Drosophilidae with an RNA virus and measured how viral load changes with temperature. We found the host phylogeny explained a large proportion of the variation in viral load at each temperature, with strong phylogenetic correlations between viral loads across temperature. The variance in viral load increased with temperature, while the mean viral load did not. This suggests that as temperature increases the most susceptible species become more susceptible, and the least susceptible less so. We found no significant relationship between a species’ susceptibility across temperatures, and proxies for thermal optima (critical thermal maximum and minimum or basal metabolic rate). These results suggest that whilst the rank order of species susceptibilities may remain the same with changes in temperature, some species may become more susceptible to a novel pathogen, and others less so.",2018 Oct 19,"['Roberts, Katherine E.', 'Hadfield, Jarrod D.', 'Sharma, Manmohan D.', 'Longdon, Ben']",PLoS Pathog,,,True
5ec99e67f23c0c2795fad1ad551ab1abe4406841,PMC,Test Paper for Colorimetric Inspection of Fatty Acids and Edible Oils,http://dx.doi.org/10.3390/s18103252,PMC6210129,30262762,CC BY,"Fatty acids (FAs) are of interest to the areas of food science and medicine because they are important dietary sources of fuel for animals and play important roles in many biological processes. The health effects of FAs are different due to the diversity of olefinic bonds in the alkyl chains including number, position and configuration. However, the discrimination of FAs is difficult from a chemical sensing perspective due to the lack of diversity in terms of functional groups. Until now, only a few chemosensors have been developed for selective sensing of FAs based on their overall shape, however they are still limited in discrimination of FAs with subtle structural differences, moreover, they cannot be used for rapid and in situ inspections. Herein, for the first time, we designed a test paper for in situ colorimetric inspection for FAs based on the combination of the highly selective binding of Ag(+) to olefinic bonds and Ag(+) mediated color variation of 3,3′,5,5′,-tetramethylbenzidine. As a result, the sensor exhibited high sensitivity and good selectivity for five FAs with subtle structural differences. Furthermore, our method described herein was successfully applied to monitor the structural variations of FAs and quality changes in mixture edible hot pot oils with heat treatment in time course. Hence, the test paper presented herein holds great potential in the inspection of fats and edible oils in food industries.",2018 Sep 27,"['Zhang, Feng', 'Wang, Xiaojie', 'Jie, Xu', 'Wei, Weili']",Sensors (Basel),,,True
c615556cb238bad03d0538519159600fe727c903,PMC,A High-Throughput Screening Approach To Repurpose FDA-Approved Drugs for Bactericidal Applications against Staphylococcus aureus Small-Colony Variants,http://dx.doi.org/10.1128/mSphere.00422-18,PMC6211227,30381352,CC BY,"Drug repurposing offers an expedited and economical route to develop new clinical therapeutics in comparison to traditional drug development. Growth-based high-throughput screening is concomitant with drug repurposing and enables rapid identification of new therapeutic uses for investigated drugs; however, this traditional method is not compatible with microorganisms with abnormal growth patterns such as Staphylococcus aureus small-colony variants (SCV). SCV subpopulations are auxotrophic for key compounds in biosynthetic pathways, which result in low growth rate. SCV formation is also associated with reduced antibiotic susceptibility, and the SCV’s ability to revert to the normal cell growth state is thought to contribute to recurrence of S. aureus infections. Thus, there is a critical need to identify antimicrobial agents that are potent against SCV in order to effectively treat chronic infections. Accordingly, here we describe adapting an adenylate kinase (AK)-based cell death reporter assay to identify members of a Food and Drug Administration (FDA)-approved drug library that display bactericidal activity against S. aureus SCV. Four library members, daunorubicin, ketoconazole, rifapentine, and sitafloxacin, exhibited potent SCV bactericidal activity against a stable S. aureus SCV. Further investigation showed that sitafloxacin was potent against methicillin-susceptible and -resistant S. aureus, as well as S. aureus within an established biofilm. Taken together, these results demonstrate the ability to use the AK assay to screen small-molecule libraries for SCV bactericidal agents and highlight the therapeutic potential of sitafloxacin to be repurposed to treat chronic S. aureus infections associated with SCV and/or biofilm growth states. IMPORTANCE Conventional antibiotics fail to successfully treat chronic osteomyelitis, endocarditis, and device-related and airway infections. These recurring infections are associated with the emergence of SCV, which are recalcitrant to conventional antibiotics. Studies have investigated antibiotic therapies to treat SCV-related infections but have had little success, emphasizing the need to identify novel antimicrobial drugs. However, drug discovery is a costly and time-consuming process. An alternative strategy is drug repurposing, which could identify FDA-approved and well-characterized drugs that could have off-label utility in treating SCV. In this study, we adapted a high-throughput AK-based assay to identify 4 FDA-approved drugs, daunorubicin, ketoconazole, rifapentine, and sitafloxacin, which display antimicrobial activity against S. aureus SCV, suggesting an avenue for drug repurposing in order to effectively treat SCV-related infections. Additionally, this screening paradigm can easily be adapted for other drug/chemical libraries to identify compounds bactericidal against SCV.",2018 Oct 31,"['Trombetta, Ryan P.', 'Dunman, Paul M.', 'Schwarz, Edward M.', 'Kates, Stephen L.', 'Awad, Hani A.']",mSphere,,,True
0450fb1cad62d6aa960e871c1dcb37ebd9620df6,PMC,"Erratum for Byukusenge et al., “Complete Genome Sequences of Four Bovine Coronavirus Isolates from Pennsylvania”",http://dx.doi.org/10.1128/MRA.00845-18,PMC6211364,30533807,CC BY,,2018 Jul 19,"['Byukusenge, Maurice', 'Nissly, Ruth Helmus', 'Kasibhatla, Sunitha Manjari', 'Li, Lingling', 'Russell, Rebekah', 'Springer, Hayley', 'Barry, Rhiannon', 'Van Saun, Robert', 'Wolfgang, David', 'Hovingh, Ernest', 'Kulkarni-Kale, Urmila', 'Kuchipudi, Suresh V.']",Microbiol Resour Announc,,,False
845b2c4662c9d7db919b0f257acecf15d97dfc81,PMC,A planarian nidovirus expands the limits of RNA genome size,http://dx.doi.org/10.1371/journal.ppat.1007314,PMC6211748,30383829,CC BY,"RNA viruses are the only known RNA-protein (RNP) entities capable of autonomous replication (albeit within a permissive host environment). A 33.5 kilobase (kb) nidovirus has been considered close to the upper size limit for such entities; conversely, the minimal cellular DNA genome is in the 100–300 kb range. This large difference presents a daunting gap for the transition from primordial RNP to contemporary DNA-RNP-based life. Whether or not RNA viruses represent transitional steps towards DNA-based life, studies of larger RNA viruses advance our understanding of the size constraints on RNP entities and the role of genome size in virus adaptation. For example, emergence of the largest previously known RNA genomes (20–34 kb in positive-stranded nidoviruses, including coronaviruses) is associated with the acquisition of a proofreading exoribonuclease (ExoN) encoded in the open reading frame 1b (ORF1b) in a monophyletic subset of nidoviruses. However, apparent constraints on the size of ORF1b, which encodes this and other key replicative enzymes, have been hypothesized to limit further expansion of these viral RNA genomes. Here, we characterize a novel nidovirus (planarian secretory cell nidovirus; PSCNV) whose disproportionately large ORF1b-like region including unannotated domains, and overall 41.1-kb genome, substantially extend the presumed limits on RNA genome size. This genome encodes a predicted 13,556-aa polyprotein in an unconventional single ORF, yet retains canonical nidoviral genome organization and expression, as well as key replicative domains. These domains may include functionally relevant substitutions rarely or never before observed in highly conserved sites of RdRp, NiRAN, ExoN and 3CLpro. Our evolutionary analysis suggests that PSCNV diverged early from multi-ORF nidoviruses, and acquired additional genes, including those typical of large DNA viruses or hosts, e.g. Ankyrin and Fibronectin type II, which might modulate virus-host interactions. PSCNV's greatly expanded genome, proteomic complexity, and unique features–impressive in themselves–attest to the likelihood of still-larger RNA genomes awaiting discovery.",2018 Nov 1,"['Saberi, Amir', 'Gulyaeva, Anastasia A.', 'Brubacher, John L.', 'Newmark, Phillip A.', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,True
bfcd50d713b8f61b51563ec3abc1afcedf01f931,PMC,A planarian nidovirus expands the limits of RNA genome size,http://dx.doi.org/10.1371/journal.ppat.1007314,PMC6211748,30383829,CC BY,"RNA viruses are the only known RNA-protein (RNP) entities capable of autonomous replication (albeit within a permissive host environment). A 33.5 kilobase (kb) nidovirus has been considered close to the upper size limit for such entities; conversely, the minimal cellular DNA genome is in the 100–300 kb range. This large difference presents a daunting gap for the transition from primordial RNP to contemporary DNA-RNP-based life. Whether or not RNA viruses represent transitional steps towards DNA-based life, studies of larger RNA viruses advance our understanding of the size constraints on RNP entities and the role of genome size in virus adaptation. For example, emergence of the largest previously known RNA genomes (20–34 kb in positive-stranded nidoviruses, including coronaviruses) is associated with the acquisition of a proofreading exoribonuclease (ExoN) encoded in the open reading frame 1b (ORF1b) in a monophyletic subset of nidoviruses. However, apparent constraints on the size of ORF1b, which encodes this and other key replicative enzymes, have been hypothesized to limit further expansion of these viral RNA genomes. Here, we characterize a novel nidovirus (planarian secretory cell nidovirus; PSCNV) whose disproportionately large ORF1b-like region including unannotated domains, and overall 41.1-kb genome, substantially extend the presumed limits on RNA genome size. This genome encodes a predicted 13,556-aa polyprotein in an unconventional single ORF, yet retains canonical nidoviral genome organization and expression, as well as key replicative domains. These domains may include functionally relevant substitutions rarely or never before observed in highly conserved sites of RdRp, NiRAN, ExoN and 3CLpro. Our evolutionary analysis suggests that PSCNV diverged early from multi-ORF nidoviruses, and acquired additional genes, including those typical of large DNA viruses or hosts, e.g. Ankyrin and Fibronectin type II, which might modulate virus-host interactions. PSCNV's greatly expanded genome, proteomic complexity, and unique features–impressive in themselves–attest to the likelihood of still-larger RNA genomes awaiting discovery.",2018 Nov 1,"['Saberi, Amir', 'Gulyaeva, Anastasia A.', 'Brubacher, John L.', 'Newmark, Phillip A.', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,True
24b00ed684ec62b0de6b45e54486cfc2422846b9,PMC,A planarian nidovirus expands the limits of RNA genome size,http://dx.doi.org/10.1371/journal.ppat.1007314,PMC6211748,30383829,CC BY,"RNA viruses are the only known RNA-protein (RNP) entities capable of autonomous replication (albeit within a permissive host environment). A 33.5 kilobase (kb) nidovirus has been considered close to the upper size limit for such entities; conversely, the minimal cellular DNA genome is in the 100–300 kb range. This large difference presents a daunting gap for the transition from primordial RNP to contemporary DNA-RNP-based life. Whether or not RNA viruses represent transitional steps towards DNA-based life, studies of larger RNA viruses advance our understanding of the size constraints on RNP entities and the role of genome size in virus adaptation. For example, emergence of the largest previously known RNA genomes (20–34 kb in positive-stranded nidoviruses, including coronaviruses) is associated with the acquisition of a proofreading exoribonuclease (ExoN) encoded in the open reading frame 1b (ORF1b) in a monophyletic subset of nidoviruses. However, apparent constraints on the size of ORF1b, which encodes this and other key replicative enzymes, have been hypothesized to limit further expansion of these viral RNA genomes. Here, we characterize a novel nidovirus (planarian secretory cell nidovirus; PSCNV) whose disproportionately large ORF1b-like region including unannotated domains, and overall 41.1-kb genome, substantially extend the presumed limits on RNA genome size. This genome encodes a predicted 13,556-aa polyprotein in an unconventional single ORF, yet retains canonical nidoviral genome organization and expression, as well as key replicative domains. These domains may include functionally relevant substitutions rarely or never before observed in highly conserved sites of RdRp, NiRAN, ExoN and 3CLpro. Our evolutionary analysis suggests that PSCNV diverged early from multi-ORF nidoviruses, and acquired additional genes, including those typical of large DNA viruses or hosts, e.g. Ankyrin and Fibronectin type II, which might modulate virus-host interactions. PSCNV's greatly expanded genome, proteomic complexity, and unique features–impressive in themselves–attest to the likelihood of still-larger RNA genomes awaiting discovery.",2018 Nov 1,"['Saberi, Amir', 'Gulyaeva, Anastasia A.', 'Brubacher, John L.', 'Newmark, Phillip A.', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,False
70d1572722a1c5180240dc458d07ec0f6794e11d,PMC,A planarian nidovirus expands the limits of RNA genome size,http://dx.doi.org/10.1371/journal.ppat.1007314,PMC6211748,30383829,CC BY,"RNA viruses are the only known RNA-protein (RNP) entities capable of autonomous replication (albeit within a permissive host environment). A 33.5 kilobase (kb) nidovirus has been considered close to the upper size limit for such entities; conversely, the minimal cellular DNA genome is in the 100–300 kb range. This large difference presents a daunting gap for the transition from primordial RNP to contemporary DNA-RNP-based life. Whether or not RNA viruses represent transitional steps towards DNA-based life, studies of larger RNA viruses advance our understanding of the size constraints on RNP entities and the role of genome size in virus adaptation. For example, emergence of the largest previously known RNA genomes (20–34 kb in positive-stranded nidoviruses, including coronaviruses) is associated with the acquisition of a proofreading exoribonuclease (ExoN) encoded in the open reading frame 1b (ORF1b) in a monophyletic subset of nidoviruses. However, apparent constraints on the size of ORF1b, which encodes this and other key replicative enzymes, have been hypothesized to limit further expansion of these viral RNA genomes. Here, we characterize a novel nidovirus (planarian secretory cell nidovirus; PSCNV) whose disproportionately large ORF1b-like region including unannotated domains, and overall 41.1-kb genome, substantially extend the presumed limits on RNA genome size. This genome encodes a predicted 13,556-aa polyprotein in an unconventional single ORF, yet retains canonical nidoviral genome organization and expression, as well as key replicative domains. These domains may include functionally relevant substitutions rarely or never before observed in highly conserved sites of RdRp, NiRAN, ExoN and 3CLpro. Our evolutionary analysis suggests that PSCNV diverged early from multi-ORF nidoviruses, and acquired additional genes, including those typical of large DNA viruses or hosts, e.g. Ankyrin and Fibronectin type II, which might modulate virus-host interactions. PSCNV's greatly expanded genome, proteomic complexity, and unique features–impressive in themselves–attest to the likelihood of still-larger RNA genomes awaiting discovery.",2018 Nov 1,"['Saberi, Amir', 'Gulyaeva, Anastasia A.', 'Brubacher, John L.', 'Newmark, Phillip A.', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,False
15963921e0161524751ac71703a1019aab29e9e0,PMC,A planarian nidovirus expands the limits of RNA genome size,http://dx.doi.org/10.1371/journal.ppat.1007314,PMC6211748,30383829,CC BY,"RNA viruses are the only known RNA-protein (RNP) entities capable of autonomous replication (albeit within a permissive host environment). A 33.5 kilobase (kb) nidovirus has been considered close to the upper size limit for such entities; conversely, the minimal cellular DNA genome is in the 100–300 kb range. This large difference presents a daunting gap for the transition from primordial RNP to contemporary DNA-RNP-based life. Whether or not RNA viruses represent transitional steps towards DNA-based life, studies of larger RNA viruses advance our understanding of the size constraints on RNP entities and the role of genome size in virus adaptation. For example, emergence of the largest previously known RNA genomes (20–34 kb in positive-stranded nidoviruses, including coronaviruses) is associated with the acquisition of a proofreading exoribonuclease (ExoN) encoded in the open reading frame 1b (ORF1b) in a monophyletic subset of nidoviruses. However, apparent constraints on the size of ORF1b, which encodes this and other key replicative enzymes, have been hypothesized to limit further expansion of these viral RNA genomes. Here, we characterize a novel nidovirus (planarian secretory cell nidovirus; PSCNV) whose disproportionately large ORF1b-like region including unannotated domains, and overall 41.1-kb genome, substantially extend the presumed limits on RNA genome size. This genome encodes a predicted 13,556-aa polyprotein in an unconventional single ORF, yet retains canonical nidoviral genome organization and expression, as well as key replicative domains. These domains may include functionally relevant substitutions rarely or never before observed in highly conserved sites of RdRp, NiRAN, ExoN and 3CLpro. Our evolutionary analysis suggests that PSCNV diverged early from multi-ORF nidoviruses, and acquired additional genes, including those typical of large DNA viruses or hosts, e.g. Ankyrin and Fibronectin type II, which might modulate virus-host interactions. PSCNV's greatly expanded genome, proteomic complexity, and unique features–impressive in themselves–attest to the likelihood of still-larger RNA genomes awaiting discovery.",2018 Nov 1,"['Saberi, Amir', 'Gulyaeva, Anastasia A.', 'Brubacher, John L.', 'Newmark, Phillip A.', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,False
a2dae2e61db2bd4eb201b98ed6051f0c489dcb6e,PMC,A planarian nidovirus expands the limits of RNA genome size,http://dx.doi.org/10.1371/journal.ppat.1007314,PMC6211748,30383829,CC BY,"RNA viruses are the only known RNA-protein (RNP) entities capable of autonomous replication (albeit within a permissive host environment). A 33.5 kilobase (kb) nidovirus has been considered close to the upper size limit for such entities; conversely, the minimal cellular DNA genome is in the 100–300 kb range. This large difference presents a daunting gap for the transition from primordial RNP to contemporary DNA-RNP-based life. Whether or not RNA viruses represent transitional steps towards DNA-based life, studies of larger RNA viruses advance our understanding of the size constraints on RNP entities and the role of genome size in virus adaptation. For example, emergence of the largest previously known RNA genomes (20–34 kb in positive-stranded nidoviruses, including coronaviruses) is associated with the acquisition of a proofreading exoribonuclease (ExoN) encoded in the open reading frame 1b (ORF1b) in a monophyletic subset of nidoviruses. However, apparent constraints on the size of ORF1b, which encodes this and other key replicative enzymes, have been hypothesized to limit further expansion of these viral RNA genomes. Here, we characterize a novel nidovirus (planarian secretory cell nidovirus; PSCNV) whose disproportionately large ORF1b-like region including unannotated domains, and overall 41.1-kb genome, substantially extend the presumed limits on RNA genome size. This genome encodes a predicted 13,556-aa polyprotein in an unconventional single ORF, yet retains canonical nidoviral genome organization and expression, as well as key replicative domains. These domains may include functionally relevant substitutions rarely or never before observed in highly conserved sites of RdRp, NiRAN, ExoN and 3CLpro. Our evolutionary analysis suggests that PSCNV diverged early from multi-ORF nidoviruses, and acquired additional genes, including those typical of large DNA viruses or hosts, e.g. Ankyrin and Fibronectin type II, which might modulate virus-host interactions. PSCNV's greatly expanded genome, proteomic complexity, and unique features–impressive in themselves–attest to the likelihood of still-larger RNA genomes awaiting discovery.",2018 Nov 1,"['Saberi, Amir', 'Gulyaeva, Anastasia A.', 'Brubacher, John L.', 'Newmark, Phillip A.', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,False
6e713159256348904f07196542ec3d7ec2e9a1a2,PMC,A planarian nidovirus expands the limits of RNA genome size,http://dx.doi.org/10.1371/journal.ppat.1007314,PMC6211748,30383829,CC BY,"RNA viruses are the only known RNA-protein (RNP) entities capable of autonomous replication (albeit within a permissive host environment). A 33.5 kilobase (kb) nidovirus has been considered close to the upper size limit for such entities; conversely, the minimal cellular DNA genome is in the 100–300 kb range. This large difference presents a daunting gap for the transition from primordial RNP to contemporary DNA-RNP-based life. Whether or not RNA viruses represent transitional steps towards DNA-based life, studies of larger RNA viruses advance our understanding of the size constraints on RNP entities and the role of genome size in virus adaptation. For example, emergence of the largest previously known RNA genomes (20–34 kb in positive-stranded nidoviruses, including coronaviruses) is associated with the acquisition of a proofreading exoribonuclease (ExoN) encoded in the open reading frame 1b (ORF1b) in a monophyletic subset of nidoviruses. However, apparent constraints on the size of ORF1b, which encodes this and other key replicative enzymes, have been hypothesized to limit further expansion of these viral RNA genomes. Here, we characterize a novel nidovirus (planarian secretory cell nidovirus; PSCNV) whose disproportionately large ORF1b-like region including unannotated domains, and overall 41.1-kb genome, substantially extend the presumed limits on RNA genome size. This genome encodes a predicted 13,556-aa polyprotein in an unconventional single ORF, yet retains canonical nidoviral genome organization and expression, as well as key replicative domains. These domains may include functionally relevant substitutions rarely or never before observed in highly conserved sites of RdRp, NiRAN, ExoN and 3CLpro. Our evolutionary analysis suggests that PSCNV diverged early from multi-ORF nidoviruses, and acquired additional genes, including those typical of large DNA viruses or hosts, e.g. Ankyrin and Fibronectin type II, which might modulate virus-host interactions. PSCNV's greatly expanded genome, proteomic complexity, and unique features–impressive in themselves–attest to the likelihood of still-larger RNA genomes awaiting discovery.",2018 Nov 1,"['Saberi, Amir', 'Gulyaeva, Anastasia A.', 'Brubacher, John L.', 'Newmark, Phillip A.', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,False
64efde7b0a9c163ba0759603a4daf7dfe446f3a8,PMC,A planarian nidovirus expands the limits of RNA genome size,http://dx.doi.org/10.1371/journal.ppat.1007314,PMC6211748,30383829,CC BY,"RNA viruses are the only known RNA-protein (RNP) entities capable of autonomous replication (albeit within a permissive host environment). A 33.5 kilobase (kb) nidovirus has been considered close to the upper size limit for such entities; conversely, the minimal cellular DNA genome is in the 100–300 kb range. This large difference presents a daunting gap for the transition from primordial RNP to contemporary DNA-RNP-based life. Whether or not RNA viruses represent transitional steps towards DNA-based life, studies of larger RNA viruses advance our understanding of the size constraints on RNP entities and the role of genome size in virus adaptation. For example, emergence of the largest previously known RNA genomes (20–34 kb in positive-stranded nidoviruses, including coronaviruses) is associated with the acquisition of a proofreading exoribonuclease (ExoN) encoded in the open reading frame 1b (ORF1b) in a monophyletic subset of nidoviruses. However, apparent constraints on the size of ORF1b, which encodes this and other key replicative enzymes, have been hypothesized to limit further expansion of these viral RNA genomes. Here, we characterize a novel nidovirus (planarian secretory cell nidovirus; PSCNV) whose disproportionately large ORF1b-like region including unannotated domains, and overall 41.1-kb genome, substantially extend the presumed limits on RNA genome size. This genome encodes a predicted 13,556-aa polyprotein in an unconventional single ORF, yet retains canonical nidoviral genome organization and expression, as well as key replicative domains. These domains may include functionally relevant substitutions rarely or never before observed in highly conserved sites of RdRp, NiRAN, ExoN and 3CLpro. Our evolutionary analysis suggests that PSCNV diverged early from multi-ORF nidoviruses, and acquired additional genes, including those typical of large DNA viruses or hosts, e.g. Ankyrin and Fibronectin type II, which might modulate virus-host interactions. PSCNV's greatly expanded genome, proteomic complexity, and unique features–impressive in themselves–attest to the likelihood of still-larger RNA genomes awaiting discovery.",2018 Nov 1,"['Saberi, Amir', 'Gulyaeva, Anastasia A.', 'Brubacher, John L.', 'Newmark, Phillip A.', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,False
59c761eaa72007b50d08705d896c18b2802e2cbb,PMC,Resolution of obstructive sleep apnea after mandibular distraction osteogenesis in setting of delayed tongue–lip adhesion takedown: A case report,http://dx.doi.org/10.1097/MD.0000000000012853,PMC6211851,30334989,CC BY,"RATIONALE: There is a high prevalence of obstructive sleep apnea (OSA) in patients with Pierre Robin sequence (PRS), and treatment approaches are highly variable. One approach is a temporary tongue-lip adhesion (TLA) that acts as a temporizing measure while the mandible continues to grow and is usually taken down at 1 year of age. PATIENT CONCERNS: Side effects of prolonged tongue-lip adhesion and optimal workup and treatment of persistent OSA in the setting of a tongue-lip adhesion. DIAGNOSES: Pierre Robin sequence (PRS), persistent obstructive sleep apnea (OSA), and tongue-lip adhesion (TLA). INTERVENTIONS: Mandibular distraction osteogenesis (MDO), adenotonsillectomy, and tongue-lip adhesion takedown. OUTCOMES: Resolution of OSA. LESSONS: This case puts into question the efficacy of isolated TLA in infants with Pierre Robin sequence and OSA, and places emphasis on the importance of considering an earlier workup of other potential causes of obstruction and the potential need for MDO as a primary or adjunctive approach to treatment.",2018 Oct 19,"['Randall, Robyn S.', 'Kian, Aaron', 'Chin, Katherine', 'French, Brooke']",Medicine (Baltimore),,,True
ca1f90fcd49058d95c081f507c5496b6b962c982,PMC,Prediction of Antimicrobial Potential of a Chemically Modified Peptide From Its Tertiary Structure,http://dx.doi.org/10.3389/fmicb.2018.02551,PMC6212470,30416494,CC BY,"Designing novel antimicrobial peptides is a hot area of research in the field of therapeutics especially after the emergence of resistant strains against the conventional antibiotics. In the past number of in silico methods have been developed for predicting the antimicrobial property of the peptide containing natural residues. This study describes models developed for predicting the antimicrobial property of a chemically modified peptide. Our models have been trained, tested and evaluated on a dataset that contains 948 antimicrobial and 931 non-antimicrobial peptides, containing chemically modified and natural residues. Firstly, the tertiary structure of all peptides has been predicted using software PEPstrMOD. Structure analysis indicates that certain type of modifications enhance the antimicrobial property of peptides. Secondly, a wide range of features was computed from the structure of these peptides using software PaDEL. Finally, models were developed for predicting the antimicrobial potential of chemically modified peptides using a wide range of structural features of these peptides. Our best model based on support vector machine achieve maximum MCC of 0.84 with an accuracy of 91.62% on training dataset and MCC of 0.80 with an accuracy of 89.89% on validation dataset. To assist the scientific community, we have developed a web server called “AntiMPmod” which predicts the antimicrobial property of the chemically modified peptide. The web server is present at the following link (http://webs.iiitd.edu.in/raghava/antimpmod/).",2018 Oct 26,"['Agrawal, Piyush', 'Raghava, Gajendra P. S.']",Front Microbiol,,,True
5a9b4ede657bcb4bd1e154dfc2b6ef0f274af4a8,PMC,Neurologic Alterations Due to Respiratory Virus Infections,http://dx.doi.org/10.3389/fncel.2018.00386,PMC6212673,30416428,CC BY,"Central Nervous System (CNS) infections are one of the most critical problems in public health, as frequently patients exhibit neurologic sequelae. Usually, CNS pathologies are caused by known neurotropic viruses such as measles virus (MV), herpes virus and human immunodeficiency virus (HIV), among others. However, nowadays respiratory viruses have placed themselves as relevant agents responsible for CNS pathologies. Among these neuropathological viruses are the human respiratory syncytial virus (hRSV), the influenza virus (IV), the coronavirus (CoV) and the human metapneumovirus (hMPV). These viral agents are leading causes of acute respiratory infections every year affecting mainly children under 5 years old and also the elderly. Up to date, several reports have described the association between respiratory viral infections with neurological symptoms. The most frequent clinical manifestations described in these patients are febrile or afebrile seizures, status epilepticus, encephalopathies and encephalitis. All these viruses have been found in cerebrospinal fluid (CSF), which suggests that all these pathogens, once in the lungs, can spread throughout the body and eventually reach the CNS. The current knowledge about the mechanisms and routes used by these neuro-invasive viruses remains scarce. In this review article, we describe the most recent findings associated to neurologic complications, along with data about the possible invasion routes of these viruses in humans and their various effects on the CNS, as studied in animal models.",2018 Oct 26,"['Bohmwald, Karen', 'Gálvez, Nicolás M. S.', 'Ríos, Mariana', 'Kalergis, Alexis M.']",Front Cell Neurosci,,,True
1703fbc6de47798061e7ec8d87182906fedab8e3,PMC,High Prevalence of MERS-CoV Infection in Camel Workers in Saudi Arabia,http://dx.doi.org/10.1128/mBio.01985-18,PMC6212820,30377284,CC BY,"Middle East respiratory syndrome (MERS), a highly lethal respiratory disease caused by a novel coronavirus (MERS-CoV), is an emerging disease with high potential for epidemic spread. It has been listed by the WHO and the Coalition for Epidemic Preparedness Innovations (CEPI) as an important target for vaccine development. While initially the majority of MERS cases were hospital acquired, continued emergence of MERS is attributed to community acquisition, with camels likely being the direct or indirect source. However, the majority of patients do not describe camel exposure, making the route of transmission unclear. Here, using sensitive immunological assays and a cohort of camel workers (CWs) with well-documented camel exposure, we show that approximately 50% of camel workers (CWs) in the Kingdom of Saudi Arabia (KSA) and 0% of controls were previously infected. We obtained blood samples from 30 camel herders, truck drivers, and handlers with well-documented camel exposure and from healthy donors, and measured MERS-CoV-specific enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), and neutralizing antibody titers, as well as T cell responses. Totals of 16/30 CWs and 0/30 healthy control donors were seropositive by MERS-CoV-specific ELISA and/or neutralizing antibody titer, and an additional four CWs were seronegative but contained virus-specific T cells in their blood. Although virus transmission from CWs has not been formally demonstrated, a possible explanation for repeated MERS outbreaks is that CWs develop mild disease and then transmit the virus to uninfected individuals. Infection of some of these individuals, such as those with comorbidities, results in severe disease and in the episodic appearance of patients with MERS.",2018 Oct 30,"['Alshukairi, Abeer N.', 'Zheng, Jian', 'Zhao, Jingxian', 'Nehdi, Atef', 'Baharoon, Salim A.', 'Layqah, Laila', 'Bokhari, Ahmad', 'Al Johani, Sameera M.', 'Samman, Nosaibah', 'Boudjelal, Mohamad', 'Ten Eyck, Patrick', 'Al-Mozaini, Maha A.', 'Zhao, Jincun', 'Perlman, Stanley', 'Alagaili, Abdulaziz N.']",mBio,,,True
dbc8339507aa0c7ce38e4343ccd543dd23f0d966,PMC,High Prevalence of MERS-CoV Infection in Camel Workers in Saudi Arabia,http://dx.doi.org/10.1128/mBio.01985-18,PMC6212820,30377284,CC BY,"Middle East respiratory syndrome (MERS), a highly lethal respiratory disease caused by a novel coronavirus (MERS-CoV), is an emerging disease with high potential for epidemic spread. It has been listed by the WHO and the Coalition for Epidemic Preparedness Innovations (CEPI) as an important target for vaccine development. While initially the majority of MERS cases were hospital acquired, continued emergence of MERS is attributed to community acquisition, with camels likely being the direct or indirect source. However, the majority of patients do not describe camel exposure, making the route of transmission unclear. Here, using sensitive immunological assays and a cohort of camel workers (CWs) with well-documented camel exposure, we show that approximately 50% of camel workers (CWs) in the Kingdom of Saudi Arabia (KSA) and 0% of controls were previously infected. We obtained blood samples from 30 camel herders, truck drivers, and handlers with well-documented camel exposure and from healthy donors, and measured MERS-CoV-specific enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), and neutralizing antibody titers, as well as T cell responses. Totals of 16/30 CWs and 0/30 healthy control donors were seropositive by MERS-CoV-specific ELISA and/or neutralizing antibody titer, and an additional four CWs were seronegative but contained virus-specific T cells in their blood. Although virus transmission from CWs has not been formally demonstrated, a possible explanation for repeated MERS outbreaks is that CWs develop mild disease and then transmit the virus to uninfected individuals. Infection of some of these individuals, such as those with comorbidities, results in severe disease and in the episodic appearance of patients with MERS.",2018 Oct 30,"['Alshukairi, Abeer N.', 'Zheng, Jian', 'Zhao, Jingxian', 'Nehdi, Atef', 'Baharoon, Salim A.', 'Layqah, Laila', 'Bokhari, Ahmad', 'Al Johani, Sameera M.', 'Samman, Nosaibah', 'Boudjelal, Mohamad', 'Ten Eyck, Patrick', 'Al-Mozaini, Maha A.', 'Zhao, Jincun', 'Perlman, Stanley', 'Alagaili, Abdulaziz N.']",mBio,,,False
ca7efbd9fc84820e4fcd442011eaba72809a7e96,PMC,High Prevalence of MERS-CoV Infection in Camel Workers in Saudi Arabia,http://dx.doi.org/10.1128/mBio.01985-18,PMC6212820,30377284,CC BY,"Middle East respiratory syndrome (MERS), a highly lethal respiratory disease caused by a novel coronavirus (MERS-CoV), is an emerging disease with high potential for epidemic spread. It has been listed by the WHO and the Coalition for Epidemic Preparedness Innovations (CEPI) as an important target for vaccine development. While initially the majority of MERS cases were hospital acquired, continued emergence of MERS is attributed to community acquisition, with camels likely being the direct or indirect source. However, the majority of patients do not describe camel exposure, making the route of transmission unclear. Here, using sensitive immunological assays and a cohort of camel workers (CWs) with well-documented camel exposure, we show that approximately 50% of camel workers (CWs) in the Kingdom of Saudi Arabia (KSA) and 0% of controls were previously infected. We obtained blood samples from 30 camel herders, truck drivers, and handlers with well-documented camel exposure and from healthy donors, and measured MERS-CoV-specific enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), and neutralizing antibody titers, as well as T cell responses. Totals of 16/30 CWs and 0/30 healthy control donors were seropositive by MERS-CoV-specific ELISA and/or neutralizing antibody titer, and an additional four CWs were seronegative but contained virus-specific T cells in their blood. Although virus transmission from CWs has not been formally demonstrated, a possible explanation for repeated MERS outbreaks is that CWs develop mild disease and then transmit the virus to uninfected individuals. Infection of some of these individuals, such as those with comorbidities, results in severe disease and in the episodic appearance of patients with MERS.",2018 Oct 30,"['Alshukairi, Abeer N.', 'Zheng, Jian', 'Zhao, Jingxian', 'Nehdi, Atef', 'Baharoon, Salim A.', 'Layqah, Laila', 'Bokhari, Ahmad', 'Al Johani, Sameera M.', 'Samman, Nosaibah', 'Boudjelal, Mohamad', 'Ten Eyck, Patrick', 'Al-Mozaini, Maha A.', 'Zhao, Jincun', 'Perlman, Stanley', 'Alagaili, Abdulaziz N.']",mBio,,,False
3512b76097c4e5282b79b7ec37e3302309fd623d,PMC,High Prevalence of MERS-CoV Infection in Camel Workers in Saudi Arabia,http://dx.doi.org/10.1128/mBio.01985-18,PMC6212820,30377284,CC BY,"Middle East respiratory syndrome (MERS), a highly lethal respiratory disease caused by a novel coronavirus (MERS-CoV), is an emerging disease with high potential for epidemic spread. It has been listed by the WHO and the Coalition for Epidemic Preparedness Innovations (CEPI) as an important target for vaccine development. While initially the majority of MERS cases were hospital acquired, continued emergence of MERS is attributed to community acquisition, with camels likely being the direct or indirect source. However, the majority of patients do not describe camel exposure, making the route of transmission unclear. Here, using sensitive immunological assays and a cohort of camel workers (CWs) with well-documented camel exposure, we show that approximately 50% of camel workers (CWs) in the Kingdom of Saudi Arabia (KSA) and 0% of controls were previously infected. We obtained blood samples from 30 camel herders, truck drivers, and handlers with well-documented camel exposure and from healthy donors, and measured MERS-CoV-specific enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), and neutralizing antibody titers, as well as T cell responses. Totals of 16/30 CWs and 0/30 healthy control donors were seropositive by MERS-CoV-specific ELISA and/or neutralizing antibody titer, and an additional four CWs were seronegative but contained virus-specific T cells in their blood. Although virus transmission from CWs has not been formally demonstrated, a possible explanation for repeated MERS outbreaks is that CWs develop mild disease and then transmit the virus to uninfected individuals. Infection of some of these individuals, such as those with comorbidities, results in severe disease and in the episodic appearance of patients with MERS.",2018 Oct 30,"['Alshukairi, Abeer N.', 'Zheng, Jian', 'Zhao, Jingxian', 'Nehdi, Atef', 'Baharoon, Salim A.', 'Layqah, Laila', 'Bokhari, Ahmad', 'Al Johani, Sameera M.', 'Samman, Nosaibah', 'Boudjelal, Mohamad', 'Ten Eyck, Patrick', 'Al-Mozaini, Maha A.', 'Zhao, Jincun', 'Perlman, Stanley', 'Alagaili, Abdulaziz N.']",mBio,,,False
5dd85144f8fc68a5a84dff8d84bd625936b97101,PMC,High Prevalence of MERS-CoV Infection in Camel Workers in Saudi Arabia,http://dx.doi.org/10.1128/mBio.01985-18,PMC6212820,30377284,CC BY,"Middle East respiratory syndrome (MERS), a highly lethal respiratory disease caused by a novel coronavirus (MERS-CoV), is an emerging disease with high potential for epidemic spread. It has been listed by the WHO and the Coalition for Epidemic Preparedness Innovations (CEPI) as an important target for vaccine development. While initially the majority of MERS cases were hospital acquired, continued emergence of MERS is attributed to community acquisition, with camels likely being the direct or indirect source. However, the majority of patients do not describe camel exposure, making the route of transmission unclear. Here, using sensitive immunological assays and a cohort of camel workers (CWs) with well-documented camel exposure, we show that approximately 50% of camel workers (CWs) in the Kingdom of Saudi Arabia (KSA) and 0% of controls were previously infected. We obtained blood samples from 30 camel herders, truck drivers, and handlers with well-documented camel exposure and from healthy donors, and measured MERS-CoV-specific enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), and neutralizing antibody titers, as well as T cell responses. Totals of 16/30 CWs and 0/30 healthy control donors were seropositive by MERS-CoV-specific ELISA and/or neutralizing antibody titer, and an additional four CWs were seronegative but contained virus-specific T cells in their blood. Although virus transmission from CWs has not been formally demonstrated, a possible explanation for repeated MERS outbreaks is that CWs develop mild disease and then transmit the virus to uninfected individuals. Infection of some of these individuals, such as those with comorbidities, results in severe disease and in the episodic appearance of patients with MERS.",2018 Oct 30,"['Alshukairi, Abeer N.', 'Zheng, Jian', 'Zhao, Jingxian', 'Nehdi, Atef', 'Baharoon, Salim A.', 'Layqah, Laila', 'Bokhari, Ahmad', 'Al Johani, Sameera M.', 'Samman, Nosaibah', 'Boudjelal, Mohamad', 'Ten Eyck, Patrick', 'Al-Mozaini, Maha A.', 'Zhao, Jincun', 'Perlman, Stanley', 'Alagaili, Abdulaziz N.']",mBio,,,False
a43db4dbbe6272ff71bcd5dc9cbf29bad9cd958e,PMC,Inhibition of Tetraspanin Functions Impairs Human Papillomavirus and Cytomegalovirus Infections,http://dx.doi.org/10.3390/ijms19103007,PMC6212908,30279342,CC BY,"Tetraspanins are suggested to regulate the composition of cell membrane components and control intracellular transport, which leaves them vulnerable to utilization by pathogens such as human papillomaviruses (HPV) and cytomegaloviruses (HCMV) to facilitate host cell entry and subsequent infection. In this study, by means of cellular depletion, the cluster of differentiation (CD) tetraspanins CD9, CD63, and CD151 were found to reduce HPV16 infection in HeLa cells by 50 to 80%. Moreover, we tested recombinant proteins or peptides of specific tetraspanin domains on their effect on the most oncogenic HPV type, HPV16, and HCMV. We found that the C-terminal tails of CD63 and CD151 significantly inhibited infections of both HPV16 and HCMV. Although CD9 was newly identified as a key cellular factor for HPV16 infection, the recombinant CD9 C-terminal peptide had no effect on infection. Based on the determined half-maximal inhibitory concentration (IC(50)), we classified CD63 and CD151 C-terminal peptides as moderate to potent inhibitors of HPV16 infection in HeLa and HaCaT cells, and in EA.hy926, HFF (human foreskin fibroblast) cells, and HEC-LTT (human endothelial cell-large T antigen and telomerase) cells for HCMV, respectively. These results indicate that HPV16 and HCMV share similar cellular requirements for their entry into host cells and reveal the necessity of the cytoplasmic CD151 and CD63 C-termini in virus infections. Furthermore, this highlights the suitability of these peptides for functional investigation of tetraspanin domains and as inhibitors of pathogen infections.",2018 Oct 2,"['Fast, Laura A.', 'Mikuličić, Snježana', 'Fritzen, Anna', 'Schwickert, Jonas', 'Boukhallouk, Fatima', 'Hochdorfer, Daniel', 'Sinzger, Christian', 'Suarez, Henar', 'Monk, Peter N.', 'Yáñez-Mó, María', 'Lieber, Diana', 'Florin, Luise']",Int J Mol Sci,,,True
77b07d4814698f7531468fc1bef3251088beca64,PMC,An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein Affects Viral RNA Synthesis and Attenuates the Virus In Vivo,http://dx.doi.org/10.3390/v10100547,PMC6212934,30301244,CC BY,"The recent outbreaks of Zika virus (ZIKV), its association with Guillain–Barré syndrome and fetal abnormalities, and the lack of approved vaccines and antivirals, highlight the importance of developing countermeasures to combat ZIKV disease. In this respect, infectious clones constitute excellent tools to accomplish these goals. However, flavivirus infectious clones are often difficult to work with due to the toxicity of some flavivirus sequences in bacteria. To bypass this problem, several alternative approaches have been applied for the generation of ZIKV clones including, among others, in vitro ligation, insertions of introns and using infectious subgenomic amplicons. Here, we report a simple and novel DNA-launched approach based on the use of a bacterial artificial chromosome (BAC) to generate a cDNA clone of Rio Grande do Norte Natal ZIKV strain. The sequence was identified from the brain tissue of an aborted fetus with microcephaly. The BAC clone was fully stable in bacteria and the infectious virus was efficiently recovered in Vero cells through direct delivery of the cDNA clone. The rescued virus yielded high titers in Vero cells and was pathogenic in a validated mouse model (A129 mice) of ZIKV infection. Furthermore, using this infectious clone we have generated a mutant ZIKV containing a single amino acid substitution (A175V) in the NS2A protein that presented reduced viral RNA synthesis in cell cultures, was highly attenuated in vivo and induced fully protection against a lethal challenge with ZIKV wild-type. This BAC approach provides a stable and reliable reverse genetic system for ZIKV that will help to identify viral determinants of virulence and facilitate the development of vaccine and therapeutic strategies.",2018 Oct 7,"['Márquez-Jurado, Silvia', 'Nogales, Aitor', 'Ávila-Pérez, Ginés', 'Iborra, Francisco J.', 'Martínez-Sobrido, Luis', 'Almazán, Fernando']",Viruses,,,True
0599be2719a0557e53ffb238765c811578a0cc9f,PMC,Development of a Rapid Fluorescent Immunochromatographic Test to Detect Respiratory Syncytial Virus,http://dx.doi.org/10.3390/ijms19103013,PMC6212954,30279406,CC BY,"Human respiratory syncytial virus (RSV) is one of the most common viruses infecting the respiratory tracts of infants. The rapid and sensitive detection of RSV is important to minimize the incidence of infection. In this study, novel monoclonal antibodies (mAbs; B11A5 and E8A11) against RSV nucleoprotein (NP) were developed and applied to develop a rapid fluorescent immunochromatographic strip test (FICT), employing europium nanoparticles as the fluorescent material. For the FICT, the limits of detection of the antigen and virus were 1.25 µg/mL and 4.23 × 10(6) TCID(50)/mL, respectively, corresponding to 4.75 × 10(6) ± 5.8 ×10(5) (mean ± SD) RNA copy numbers per reaction mixture for RSV NP. A clinical study revealed a sensitivity of 90% (18/20) and specificity of 98.18% (108/110) for RSV detection when comparing the performance to that of reverse transcription polymerase chain reaction (RT-PCR), representing a 15% improvement in sensitivity over the SD Bioline rapid kit. This newly developed FICT could be a useful tool for the rapid diagnosis of RSV infection.",2018 Oct 2,"['Thuy Tien, Trinh Thi', 'Park, Hyun', 'Tuong, Hien Thi', 'Yu, Seung-Taek', 'Choi, Du-Young', 'Yeo, Seon-Ju']",Int J Mol Sci,,,True
285852264b2c14f53cff87f8ae9ef7738892aa3f,PMC,Development of a Rapid Fluorescent Immunochromatographic Test to Detect Respiratory Syncytial Virus,http://dx.doi.org/10.3390/ijms19103013,PMC6212954,30279406,CC BY,"Human respiratory syncytial virus (RSV) is one of the most common viruses infecting the respiratory tracts of infants. The rapid and sensitive detection of RSV is important to minimize the incidence of infection. In this study, novel monoclonal antibodies (mAbs; B11A5 and E8A11) against RSV nucleoprotein (NP) were developed and applied to develop a rapid fluorescent immunochromatographic strip test (FICT), employing europium nanoparticles as the fluorescent material. For the FICT, the limits of detection of the antigen and virus were 1.25 µg/mL and 4.23 × 10(6) TCID(50)/mL, respectively, corresponding to 4.75 × 10(6) ± 5.8 ×10(5) (mean ± SD) RNA copy numbers per reaction mixture for RSV NP. A clinical study revealed a sensitivity of 90% (18/20) and specificity of 98.18% (108/110) for RSV detection when comparing the performance to that of reverse transcription polymerase chain reaction (RT-PCR), representing a 15% improvement in sensitivity over the SD Bioline rapid kit. This newly developed FICT could be a useful tool for the rapid diagnosis of RSV infection.",2018 Oct 2,"['Thuy Tien, Trinh Thi', 'Park, Hyun', 'Tuong, Hien Thi', 'Yu, Seung-Taek', 'Choi, Du-Young', 'Yeo, Seon-Ju']",Int J Mol Sci,,,False
e7188ee8f88af646369d7db34c99658cc80206c0,PMC,Role of Host Cell Secretory Machinery in Zika Virus Life Cycle,http://dx.doi.org/10.3390/v10100559,PMC6213159,30326556,CC BY,"The high human cost of Zika virus infections and the rapid establishment of virus circulation in novel areas, including the United States, present an urgent need for countermeasures against this emerging threat. The development of an effective vaccine against Zika virus may be problematic because of the cross reactivity of the antibodies with other flaviviruses leading to antibody-dependent enhancement of infection. Moreover, rapidly replicating positive strand RNA viruses, including Zika virus, generate large spectrum of mutant genomes (quasi species) every replication round, allowing rapid selection of variants resistant to drugs targeting virus-specific proteins. On the other hand, viruses are ultimate cellular parasites and rely on the host metabolism for every step of their life cycle, thus presenting an opportunity to manipulate host processes as an alternative approach to suppress virus replication and spread. Zika and other flaviviruses critically depend on the cellular secretory pathway, which transfers proteins and membranes from the ER through the Golgi to the plasma membrane, for virion assembly, maturation and release. In this review, we summarize the current knowledge of interactions of Zika and similar arthropod-borne flaviviruses with the cellular secretory machinery with a special emphasis on virus-specific changes of the secretory pathway. Identification of the regulatory networks and effector proteins required to accommodate the trafficking of virions, which represent a highly unusual cargo for the secretory pathway, may open an attractive and virtually untapped reservoir of alternative targets for the development of superior anti-viral drugs.",2018 Oct 15,"['Sager, Garrett', 'Gabaglio, Samuel', 'Sztul, Elizabeth', 'Belov, George A.']",Viruses,,,True
2813c9a864720f35199261a3ab219750d3a5daeb,PMC,The Characterization of Immunoprotection Induced by a cDNA Clone Derived from the Attenuated Taiwan Porcine Epidemic Diarrhea Virus Pintung 52 Strain,http://dx.doi.org/10.3390/v10100543,PMC6213177,30287770,CC BY,"The porcine epidemic diarrhea virus (PEDV) poses a great threat to the global swine industries and the unreliable protection induced by the currently available vaccines remains a major challenge. We previously generated a genogroup 2b (G2b) PEDV Taiwan Pintung 52 (PEDVPT) strain, PEDVPT-P96, and determined its promising host immune response against the virulent PEDVPT-P5 strain. To study the attenuation determinants of PEDVPT-P96 and establish a PEDVPT-P96-based recombinant vector as a vaccine platform for further antigenicity modification, iPEDVPT-P96, a full-length cDNA clone of PEDVPT-P96, was established. Comparing to the parental PEDVPT-P96 virus, the iPEDVPT-P96 virus showed efficient replication kinetics with a delayed decline of viral load and similar but much more uniform plaque sizes in Vero cells. In the 5-week-old piglet model, fecal viral shedding was observed in the PEDVPT-P96-inoculated piglets, whereas those inoculated with iPEDVPT-P96 showed neither detectable fecal viral shedding nor PEDV-associated clinical signs. Moreover, inoculation with iPEDVPT-P96 elicited comparable levels of anti-PEDV specific plasma IgG and fecal/salivary IgA, neutralizing antibody titers, and similar but less effective immunoprotection against the virulent PEDVPT-P5 challenge compared to the parental PEDVPT-P96. In the present study, an infectious cDNA clone of an attenuated G2b PEDV strain was successfully generated for the first time, and the in vitro and in vivo data indicate that iPEDVPT-P96 is further attenuated but remains immunogenic compared to its parental PEDVPT-P96 viral stock. The successful development of the iPEDVPT-P96 cDNA clone could allow for the manipulation of the viral genome to study viral pathogenesis and facilitate the rapid development of effective vaccines.",2018 Oct 4,"['Kao, Chi-Fei', 'Chiou, Hue-Ying', 'Chang, Yen-Chen', 'Hsueh, Cheng-Shun', 'Jeng, Chian-Ren', 'Tsai, Pei-Shiue', 'Cheng, Ivan-Chen', 'Pang, Victor Fei', 'Chang, Hui-Wen']",Viruses,,,True
2e54633cb21514db8594a202a69a87dc2ad05520,PMC,The Characterization of Immunoprotection Induced by a cDNA Clone Derived from the Attenuated Taiwan Porcine Epidemic Diarrhea Virus Pintung 52 Strain,http://dx.doi.org/10.3390/v10100543,PMC6213177,30287770,CC BY,"The porcine epidemic diarrhea virus (PEDV) poses a great threat to the global swine industries and the unreliable protection induced by the currently available vaccines remains a major challenge. We previously generated a genogroup 2b (G2b) PEDV Taiwan Pintung 52 (PEDVPT) strain, PEDVPT-P96, and determined its promising host immune response against the virulent PEDVPT-P5 strain. To study the attenuation determinants of PEDVPT-P96 and establish a PEDVPT-P96-based recombinant vector as a vaccine platform for further antigenicity modification, iPEDVPT-P96, a full-length cDNA clone of PEDVPT-P96, was established. Comparing to the parental PEDVPT-P96 virus, the iPEDVPT-P96 virus showed efficient replication kinetics with a delayed decline of viral load and similar but much more uniform plaque sizes in Vero cells. In the 5-week-old piglet model, fecal viral shedding was observed in the PEDVPT-P96-inoculated piglets, whereas those inoculated with iPEDVPT-P96 showed neither detectable fecal viral shedding nor PEDV-associated clinical signs. Moreover, inoculation with iPEDVPT-P96 elicited comparable levels of anti-PEDV specific plasma IgG and fecal/salivary IgA, neutralizing antibody titers, and similar but less effective immunoprotection against the virulent PEDVPT-P5 challenge compared to the parental PEDVPT-P96. In the present study, an infectious cDNA clone of an attenuated G2b PEDV strain was successfully generated for the first time, and the in vitro and in vivo data indicate that iPEDVPT-P96 is further attenuated but remains immunogenic compared to its parental PEDVPT-P96 viral stock. The successful development of the iPEDVPT-P96 cDNA clone could allow for the manipulation of the viral genome to study viral pathogenesis and facilitate the rapid development of effective vaccines.",2018 Oct 4,"['Kao, Chi-Fei', 'Chiou, Hue-Ying', 'Chang, Yen-Chen', 'Hsueh, Cheng-Shun', 'Jeng, Chian-Ren', 'Tsai, Pei-Shiue', 'Cheng, Ivan-Chen', 'Pang, Victor Fei', 'Chang, Hui-Wen']",Viruses,,,False
6844a1c61fe924441532dad545f96e1d6a6d677c,PMC,Ocular Manifestations of Emerging Flaviviruses and the Blood-Retinal Barrier,http://dx.doi.org/10.3390/v10100530,PMC6213219,30274199,CC BY,"Despite flaviviruses remaining the leading cause of systemic human infections worldwide, ocular manifestations of these mosquito-transmitted viruses are considered relatively uncommon in part due to under-reporting. However, recent outbreaks of Zika virus (ZIKV) implicated in causing multiple ocular abnormalities, such as conjunctivitis, retinal hemorrhages, chorioretinal atrophy, posterior uveitis, optic neuritis, and maculopathies, has rejuvenated a significant interest in understanding the pathogenesis of flaviviruses, including ZIKV, in the eye. In this review, first, we summarize the current knowledge of the major flaviviruses (Dengue, West Nile, Yellow Fever, and Japanese Encephalitis) reported to cause ocular manifestations in humans with emphasis on recent ZIKV outbreaks. Second, being an immune privilege organ, the eye is protected from systemic infections by the presence of blood-retinal barriers (BRB). Hence, we discuss how flaviviruses modulate retinal innate response and breach the protective BRB to cause ocular or retinal pathology. Finally, we describe recently identified infection signatures of ZIKV and discuss whether these system biology-predicted genes or signaling pathways (e.g., cellular metabolism) could contribute to the pathogenesis of ocular manifestations and assist in the development of ocular antiviral therapies against ZIKV and other flaviviruses.",2018 Sep 28,"['Singh, Sneha', 'Kumar, Ashok']",Viruses,,,True
0396bc111213d601eeb67ae191530309bdbb6220,PMC,Exchange Protein Directly Activated by cAMP Modulates Ebola Virus Uptake into Vascular Endothelial Cells,http://dx.doi.org/10.3390/v10100563,PMC6213290,30332733,CC BY,"Members of the family Filoviridae, including Ebola virus (EBOV) and Marburg virus (MARV), cause severe hemorrhagic fever in humans and nonhuman primates. Given their high lethality, a comprehensive understanding of filoviral pathogenesis is urgently needed. In the present studies, we revealed that the exchange protein directly activated by cAMP 1 (EPAC1) gene deletion protects vasculature in ex vivo explants from EBOV infection. Importantly, pharmacological inhibition of EPAC1 using EPAC-specific inhibitors (ESIs) mimicked the EPAC1 knockout phenotype in the ex vivo model. ESI treatment dramatically decreased EBOV infectivity in both ex vivo vasculature and in vitro vascular endothelial cells (ECs). Furthermore, postexposure protection of ECs against EBOV infection was conferred using ESIs. Protective efficacy of ESIs in ECs was observed also in MARV infection. Additional studies using a vesicular stomatitis virus pseudotype that expresses EBOV glycoprotein (EGP-VSV) confirmed that ESIs reduced infection in ECs. Ultrastructural studies suggested that ESIs blocked EGP-VSV internalization via inhibition of macropinocytosis. The inactivation of EPAC1 affects the early stage of viral entry after viral binding to the cell surface, but before early endosome formation, in a phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-dependent manner. Our study delineated a new critical role of EPAC1 during EBOV uptake into ECs.",2018 Oct 16,"['Drelich, Aleksandra', 'Judy, Barbara', 'He, Xi', 'Chang, Qing', 'Yu, Shangyi', 'Li, Xiang', 'Lu, Fanglin', 'Wakamiya, Maki', 'Popov, Vsevolod', 'Zhou, Jia', 'Ksiazek, Thomas', 'Gong, Bin']",Viruses,,,True
77f331c73a874a86f6109346c3b798593b75fa5e,PMC,Exchange Protein Directly Activated by cAMP Modulates Ebola Virus Uptake into Vascular Endothelial Cells,http://dx.doi.org/10.3390/v10100563,PMC6213290,30332733,CC BY,"Members of the family Filoviridae, including Ebola virus (EBOV) and Marburg virus (MARV), cause severe hemorrhagic fever in humans and nonhuman primates. Given their high lethality, a comprehensive understanding of filoviral pathogenesis is urgently needed. In the present studies, we revealed that the exchange protein directly activated by cAMP 1 (EPAC1) gene deletion protects vasculature in ex vivo explants from EBOV infection. Importantly, pharmacological inhibition of EPAC1 using EPAC-specific inhibitors (ESIs) mimicked the EPAC1 knockout phenotype in the ex vivo model. ESI treatment dramatically decreased EBOV infectivity in both ex vivo vasculature and in vitro vascular endothelial cells (ECs). Furthermore, postexposure protection of ECs against EBOV infection was conferred using ESIs. Protective efficacy of ESIs in ECs was observed also in MARV infection. Additional studies using a vesicular stomatitis virus pseudotype that expresses EBOV glycoprotein (EGP-VSV) confirmed that ESIs reduced infection in ECs. Ultrastructural studies suggested that ESIs blocked EGP-VSV internalization via inhibition of macropinocytosis. The inactivation of EPAC1 affects the early stage of viral entry after viral binding to the cell surface, but before early endosome formation, in a phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-dependent manner. Our study delineated a new critical role of EPAC1 during EBOV uptake into ECs.",2018 Oct 16,"['Drelich, Aleksandra', 'Judy, Barbara', 'He, Xi', 'Chang, Qing', 'Yu, Shangyi', 'Li, Xiang', 'Lu, Fanglin', 'Wakamiya, Maki', 'Popov, Vsevolod', 'Zhou, Jia', 'Ksiazek, Thomas', 'Gong, Bin']",Viruses,,,True
84bafc34e5e1118ed2da16a02c87e472e0dd0d4c,PMC,"CEACAM1 in Liver Injury, Metabolic and Immune Regulation",http://dx.doi.org/10.3390/ijms19103110,PMC6213298,30314283,CC BY,"Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a transmembrane glycoprotein that is expressed on epithelial, endothelial and immune cells. CEACAM1 is a differentiation antigen involved in the maintenance of epithelial polarity that is induced during hepatocyte differentiation and liver regeneration. CEACAM1 regulates insulin sensitivity by promoting hepatic insulin clearance, and controls liver tolerance and mucosal immunity. Obese insulin-resistant humans with non-alcoholic fatty liver disease manifest loss of hepatic CEACAM1. In mice, deletion or functional inactivation of CEACAM1 impairs insulin clearance and compromises metabolic homeostasis which initiates the development of obesity and hepatic steatosis and fibrosis with other features of non-alcoholic steatohepatitis, and adipogenesis in white adipose depot. This is followed by inflammation and endothelial and cardiovascular dysfunctions. In obstructive and inflammatory liver diseases, soluble CEACAM1 is shed into human bile where it can serve as an indicator of liver disease. On immune cells, CEACAM1 acts as an immune checkpoint regulator, and deletion of Ceacam1 gene in mice causes exacerbation of inflammation and hyperactivation of myeloid cells and lymphocytes. Hence, hepatic CEACAM1 resides at the central hub of immune and metabolic homeostasis in both humans and mice. This review focuses on the regulatory role of CEACAM1 in liver and biliary tract architecture in health and disease, and on its metabolic role and function as an immune checkpoint regulator of hepatic inflammation.",2018 Oct 11,"['Horst, Andrea Kristina', 'Najjar, Sonia M.', 'Wagener, Christoph', 'Tiegs, Gisa']",Int J Mol Sci,,,True
f869e0515c1a31c8d4c1770a053ce1d933c30241,PMC,Photodynamic Inactivation of Herpes Simplex Viruses,http://dx.doi.org/10.3390/v10100532,PMC6213367,30274257,CC BY,"Herpes simplex virus (HSV) infections can be treated with direct acting antivirals like acyclovir and foscarnet, but long-term use can lead to drug resistance, which motivates research into broadly-acting antivirals that can provide a greater genetic barrier to resistance. Photodynamic inactivation (PDI) employs a photosensitizer, light, and oxygen to create a local burst of reactive oxygen species that inactivate microorganisms. The botanical plant extract Orthoquin(TM) is a powerful photosensitizer with antimicrobial properties. Here we report that Orthoquin also has antiviral properties. Photoactivated Orthoquin inhibited herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infection of target cells in a dose-dependent manner across a broad range of sub-cytotoxic concentrations. HSV inactivation required direct contact between Orthoquin and the inoculum, whereas pre-treatment of target cells had no effect. Orthoquin did not cause appreciable damage to viral capsids or premature release of viral genomes, as measured by qPCR for the HSV-1 genome. By contrast, immunoblotting for HSV-1 antigens in purified virion preparations suggested that higher doses of Orthoquin had a physical impact on certain HSV-1 proteins that altered protein mobility or antigen detection. Orthoquin PDI also inhibited the non-enveloped adenovirus (AdV) in a dose-dependent manner, whereas Orthoquin-mediated inhibition of the enveloped vesicular stomatitis virus (VSV) was light-independent. Together, these findings suggest that the broad antiviral effects of Orthoquin-mediated PDI may stem from damage to viral attachment proteins.",2018 Sep 29,"['Monjo, Andrea L.-A.', 'Pringle, Eric S.', 'Thornbury, Mackenzie', 'Duguay, Brett A.', 'Monro, Susan M. A.', 'Hetu, Marc', 'Knight, Danika', 'Cameron, Colin G.', 'McFarland, Sherri A.', 'McCormick, Craig']",Viruses,,,True
a576b341e354b09d299d85220586219f18a9bef2,PMC,Nucleic Acid-Dependent Structural Transition of the Intrinsically Disordered N-Terminal Appended Domain of Human Lysyl-tRNA Synthetase,http://dx.doi.org/10.3390/ijms19103016,PMC6213541,30282926,CC BY,"Eukaryotic lysyl-tRNA synthetases (LysRS) have an N-terminal appended tRNA-interaction domain (RID) that is absent in their prokaryotic counterparts. This domain is intrinsically disordered and lacks stable structures. The disorder-to-order transition is induced by tRNA binding and has implications on folding and subsequent assembly into multi-tRNA synthetase complexes. Here, we expressed and purified RID from human LysRS (hRID) in Escherichia coli and performed a detailed mutagenesis of the appended domain. hRID was co-purified with nucleic acids during Ni-affinity purification, and cumulative mutations on critical amino acid residues abolished RNA binding. Furthermore, we identified a structural ensemble between disordered and helical structures in non-RNA-binding mutants and an equilibrium shift for wild-type into the helical conformation upon RNA binding. Since mutations that disrupted RNA binding led to an increase in non-functional soluble aggregates, a stabilized RNA-mediated structural transition of the N-terminal appended domain may have implications on the functional organization of human LysRS and multi-tRNA synthetase complexes in vivo.",2018 Oct 3,"['Kwon, Soon Bin', 'Yu, Ji Eun', 'Park, Chan', 'Lee, Jiseop', 'Seong, Baik L.']",Int J Mol Sci,,,True
884bb2d874509df6e469fca856c3ebdf03a61e1c,PMC,Nucleic Acid-Dependent Structural Transition of the Intrinsically Disordered N-Terminal Appended Domain of Human Lysyl-tRNA Synthetase,http://dx.doi.org/10.3390/ijms19103016,PMC6213541,30282926,CC BY,"Eukaryotic lysyl-tRNA synthetases (LysRS) have an N-terminal appended tRNA-interaction domain (RID) that is absent in their prokaryotic counterparts. This domain is intrinsically disordered and lacks stable structures. The disorder-to-order transition is induced by tRNA binding and has implications on folding and subsequent assembly into multi-tRNA synthetase complexes. Here, we expressed and purified RID from human LysRS (hRID) in Escherichia coli and performed a detailed mutagenesis of the appended domain. hRID was co-purified with nucleic acids during Ni-affinity purification, and cumulative mutations on critical amino acid residues abolished RNA binding. Furthermore, we identified a structural ensemble between disordered and helical structures in non-RNA-binding mutants and an equilibrium shift for wild-type into the helical conformation upon RNA binding. Since mutations that disrupted RNA binding led to an increase in non-functional soluble aggregates, a stabilized RNA-mediated structural transition of the N-terminal appended domain may have implications on the functional organization of human LysRS and multi-tRNA synthetase complexes in vivo.",2018 Oct 3,"['Kwon, Soon Bin', 'Yu, Ji Eun', 'Park, Chan', 'Lee, Jiseop', 'Seong, Baik L.']",Int J Mol Sci,,,False
f16da7cf7a952fb981dfc0d77280aac9c3ab933a,PMC,"Ebola Virus Maintenance: If Not (Only) Bats, What Else?",http://dx.doi.org/10.3390/v10100549,PMC6213544,30304789,CC BY,"The maintenance mechanisms of ebolaviruses in African forest ecosystems are still unknown, but indirect evidences point at the involvement of some bat species. Despite intense research, the main bat-maintenance hypothesis has not been confirmed yet. The alternative hypotheses of a non-bat maintenance host or a maintenance community including, or not, several bat and other species, deserves more investigation. However, African forest ecosystems host a large biodiversity and abound in potential maintenance hosts. How does one puzzle out? Since recent studies have revealed that several bat species have been exposed to ebolaviruses, the common denominator to these hypotheses is that within the epidemiological cycle, some bats species must be exposed to the viruses and infected by these potential alternative hosts. Under this constraint, and given the peculiar ecology of bats (roosting behaviour, habitat utilisation, and flight mode), we review the hosts and transmission pathways that can lead to bat exposure and infection to ebolaviruses. In contrast to the capacity of bats to transmit ebolaviruses and other pathogens to many hosts, our results indicate that only a limited number of hosts and pathways can lead to the transmission of ebolaviruses to bats, and that the alternative maintenance host, if it exists, must be amongst them. A list of these pathways is provided, along with protocols to prioritise and investigate these alternative hypotheses. In conclusion, taking into account the ecology of bats and their known involvement in ebolaviruses ecology drastically reduces the list of potential alternative maintenance hosts for ebolaviruses. Understanding the natural history of ebolaviruses is a health priority, and investigating these alternative hypotheses could complete the current effort focused on the role of bats.",2018 Oct 9,"['Caron, Alexandre', 'Bourgarel, Mathieu', 'Cappelle, Julien', 'Liégeois, Florian', 'De Nys, Hélène M.', 'Roger, François']",Viruses,,,True
2f48db348bec8a09f6a83d949d1a3294fbe44008,PMC,"Human Coronavirus Infections in Israel: Epidemiology, Clinical Symptoms and Summer Seasonality of HCoV-HKU1",http://dx.doi.org/10.3390/v10100515,PMC6213580,30241410,CC BY,"Human coronaviruses (HCoVs) cause mild to severe respiratory diseases. Six types of HCoVs have been discovered, the most recent one termed the Middle East respiratory syndrome coronavirus (MERS-CoV). The aim of this study is to monitor the circulation of HCoV types in the population during 2015–2016 in Israel. HCoVs were detected by real-time PCR analysis in 1910 respiratory samples, collected from influenza-like illness (ILI) patients during the winter sentinel influenza survey across Israel. Moreover, 195 HCoV-positive samples from hospitalized patients were detected during one year at Soroka University Medical Center. While no MERS-CoV infections were detected, 10.36% of patients in the survey were infected with HCoV-OC43 (43.43%), HCoV-NL63 (44.95%), and HCoV-229E (11.62%) viruses. The HCoVs were shown to co-circulate with respiratory syncytial virus (RSV) and to appear prior to influenza virus infections. HCoV clinical symptoms were more severe than those of RSV infections but milder than influenza symptoms. Hospitalized patients had similar HCoV types percentages. However, while it was absent from the public winter survey, 22.6% of the patients were HCoV-HKU1 positives, mainly during the spring-summer period.",2018 Sep 21,"['Friedman, Nehemya', 'Alter, Hadar', 'Hindiyeh, Musa', 'Mendelson, Ella', 'Shemer Avni, Yonat', 'Mandelboim, Michal']",Viruses,,,True
ba7a8a3ea4005fb471ec2ff975634765f729c32f,PMC,Temperature Sensitive Mutations in Influenza A Viral Ribonucleoprotein Complex Responsible for the Attenuation of the Live Attenuated Influenza Vaccine,http://dx.doi.org/10.3390/v10100560,PMC6213772,30326610,CC BY,"Live attenuated influenza vaccines (LAIV) have prevented morbidity and mortality associated with influenza viral infections for many years and represent the best therapeutic option to protect against influenza viral infections in humans. However, the development of LAIV has traditionally relied on empirical methods, such as the adaptation of viruses to replicate at low temperatures. These approaches require an extensive investment of time and resources before identifying potential vaccine candidates that can be safely implemented as LAIV to protect humans. In addition, the mechanism of attenuation of these vaccines is poorly understood in some cases. Importantly, LAIV are more efficacious than inactivated vaccines because their ability to mount efficient innate and adaptive humoral and cellular immune responses. Therefore, the design of potential LAIV based on known properties of viral proteins appears to be a highly appropriate option for the treatment of influenza viral infections. For that, the viral RNA synthesis machinery has been a research focus to identify key amino acid substitutions that can lead to viral attenuation and their use in safe, immunogenic, and protective LAIV. In this review, we discuss the potential to manipulate the influenza viral RNA-dependent RNA polymerase (RdRp) complex to generate attenuated forms of the virus that can be used as LAIV for the treatment of influenza viral infections, one of the current and most effective prophylactic options for the control of influenza in humans.",2018 Oct 15,"['Martínez-Sobrido, Luis', 'Peersen, Olve', 'Nogales, Aitor']",Viruses,,,True
77dc3c4e78b6fe5c233613de24779897f673bb9c,PMC,Traditional Chinese Medicine as a Potential Source for HSV-1 Therapy by Acting on Virus or the Susceptibility of Host,http://dx.doi.org/10.3390/ijms19103266,PMC6213986,30347851,CC BY,"Herpes simplex virus type 1 (HSV-1) is the most common virus, with an estimated infection rate of 60–95% among the adult population. Once infected, HSV-1 can remain latent in the host for a lifetime and be reactivated in patients with a compromised immune system. Reactivation of latent HSV-1 can also be achieved by other stimuli. Though acyclovir (ACV) is a classic drug for HSV-1 infection, ACV-resistant strains have been found in immune-compromised patients and drug toxicity has also been commonly reported. Therefore, there is an urge to search for new anti-HSV-1 agents. Natural products with potential anti-HSV-1 activity have the advantages of minimal side effects, reduced toxicity, and they exert their effect by various mechanisms. This paper will not only provide a reference for the safe dose of these agents if they are to be used in humans, referring to the interrelated data obtained from in vitro experiments, but also introduce the main pharmacodynamic mechanisms of traditional Chinese medicine (TCM) against HSV-1. Taken together, TCM functions as a potential source for HSV-1 therapy by direct (blocking viral attachment/absorption/penetration/replication) or indirect (reducing the susceptibility to HSV-1 or regulating autophagy) antiviral activities. The potential of these active components in the development of anti-HSV-1 drugs will also be described.",2018 Oct 20,"['Li, Wen', 'Wang, Xiao-Hua', 'Luo, Zhuo', 'Liu, Li-Fang', 'Yan, Chang', 'Yan, Chang-Yu', 'Chen, Guo-Dong', 'Gao, Hao', 'Duan, Wen-Jun', 'Kurihara, Hiroshi', 'Li, Yi-Fang', 'He, Rong-Rong']",Int J Mol Sci,,,True
5fb9518f07541bb5ee6f8f9ef9d374416ffeecc7,PMC,"Non-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide",http://dx.doi.org/10.3390/ijms19103248,PMC6214015,30347750,CC BY,"Lack of endothelial nitric oxide causes endothelial dysfunction and circulating monocyte infiltration, contributing to systemic atheroma plaque formation in arterial territories. Among the different inflammatory products, macrophage-derived foam cells and smooth muscle cells synthesize matrix metalloproteinases (MMPs), playing a pivotal role in early plaque formation and enlargement. We found increased levels of MMP-9 and MMP-13 in human endarterectomies with advanced atherosclerosis, together with significant amounts of extracellular matrix (ECM) metalloproteinase inducer EMMPRIN. To test whether the absence of NO may aggravate atherosclerosis through EMMPRIN activation, double NOS3/apoE knockout (KO) mice expressed high levels of EMMPRIN in carotid plaques, suggesting that targeting extracellular matrix degradation may represent a new mechanism by which endothelial NO prevents atherosclerosis. Based on our previous experience, by using gadolinium-enriched paramagnetic fluorescence micellar nanoparticles conjugated with AP9 (NAP9), an EMMPRIN-specific binding peptide, magnetic resonance sequences allowed non-invasive visualization of carotid EMMPRIN in NOS3/apoE over apoE control mice, in which atheroma plaques were significantly reduced. Taken together, these results point to EMMPRIN as a new therapeutic target of NO-mediated protection against atherosclerosis, and NAP9 as a non-invasive molecular tool to target atherosclerosis.",2018 Oct 19,"['Ramirez-Carracedo, Rafael', 'Tesoro, Laura', 'Hernandez, Ignacio', 'Diez-Mata, Javier', 'Filice, Marco', 'Toro, Rocío', 'Rodriguez-Piñero, Manuel', 'Zamorano, Jose Luis', 'Saura, Marta', 'Zaragoza, Carlos']",Int J Mol Sci,,,True
181bef55321b315c053d17800f248442f38d15fa,PMC,"Dynamic graphs, community detection, and Riemannian geometry",http://dx.doi.org/10.1007/s41109-018-0059-2,PMC6214282,30839776,CC BY,"A community is a subset of a wider network where the members of that subset are more strongly connected to each other than they are to the rest of the network. In this paper, we consider the problem of identifying and tracking communities in graphs that change over time – dynamic community detection – and present a framework based on Riemannian geometry to aid in this task. Our framework currently supports several important operations such as interpolating between and averaging over graph snapshots. We compare these Riemannian methods with entry-wise linear interpolation and find that the Riemannian methods are generally better suited to dynamic community detection. Next steps with the Riemannian framework include producing a Riemannian least-squares regression method for working with noisy data and developing support methods, such as spectral sparsification, to improve the scalability of our current methods. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s41109-018-0059-2) contains supplementary material, which is available to authorized users.",2018 Mar 29,"['Bakker, Craig', 'Halappanavar, Mahantesh', 'Visweswara Sathanur, Arun']",Appl Netw Sci,,,True
410252e2a079c3b04f48b19672baa63bc8e7ebe4,PMC,Zoonotic disease research in East Africa,http://dx.doi.org/10.1186/s12879-018-3443-8,PMC6215645,30390630,CC BY,"BACKGROUND: The East African region is endemic with multiple zoonotic diseases and is one of the hotspots for emerging infectious zoonotic diseases with reported multiple outbreaks of epidemic diseases such as Ebola, Marburg and Rift Valley Fever. Here we present a systematic assessment of published research on zoonotic diseases in the region and thesis research in Kenya to understand the regional research focus and trends in publications, and estimate proportion of theses research transitioning to peer-reviewed journal publications. METHODS: We searched PubMed, Google Scholar and African Journals Online databases for publications on 36 zoonotic diseases identified to have occurred in the East Africa countries of Burundi, Ethiopia, Kenya, Tanzania, Rwanda and Uganda, for the period between 1920 and 2017. We searched libraries and queried online repositories for masters and PhD theses on these diseases produced between 1970 and 2016 in five universities and two research institutions in Kenya. RESULTS: We identified 771 journal articles on 22, and 168 theses on 21 of the 36 zoonotic diseases investigated. Research on zoonotic diseases increased exponentially with the last 10 years of our study period contributing more than half of all publications 460 (60%) and theses 102 (61%) retrieved. Endemic diseases were the most studied accounting for 656 (85%) and 150 (89%) of the publication and theses studies respectively, with publications on epidemic diseases associated with outbreaks reported in the region or elsewhere. Epidemiological studies were the most common study types but limited to cross-sectional studies while socio-economics were the least studied. Only 11% of the theses research transitioned to peer-review publications, taking an average of 2.5 years from theses production to manuscript publication. CONCLUSION: Our findings demonstrate increased attention to zoonotic diseases in East Africa but reveal the need to expand the scope, focus and quality of studies to adequately address the public health, social and economic threats posed by zoonoses.",2018 Nov 3,"['Kemunto, Naomi', 'Mogoa, Eddy', 'Osoro, Eric', 'Bitek, Austin', 'Kariuki Njenga, M.', 'Thumbi, S. M.']",BMC Infect Dis,,,True
87797599a00816e5bc19e3804da8af1778d61b0c,PMC,Complete blood count data and leukocyte expression of cytokine genes and cytokine receptor genes associated with bovine respiratory disease in calves,http://dx.doi.org/10.1186/s13104-018-3900-x,PMC6215650,30390697,CC BY,"OBJECTIVE: The purpose of this study was to evaluate potential relationships between cytokine gene expression, complete blood counts (CBC) and animals that were sick or would become sick. The CBC and the transcript abundance of cytokines and their receptors expressed in leukocytes were measured from calves at two early timepoints, and again after diagnosis with bovine respiratory disease (BRD). RESULTS: Blood was collected from calves at pre-conditioning (n = 796) and weaning (n = 791) for CBC. Blood counts were also measured for the calves with BRD (n = 13), and asymptomatic calves (n = 75) after weaning. The CBC were compared for these animals at 3 time points. At diagnosis, neutrophils were higher and basophils lower in sick animals (P < 0.05). To further characterize BRD responses, transcript abundance of 84 cytokine genes were evaluated in 5 calves with BRD and 9 asymptomatic animals at all time points. There was more data for CBC than transcript abundance; hence, animal and temporary environmental correlations between CBC and transcript abundance were exploited to improve the power of the transcript abundance data. Expression of CCL16, CXCR1, CCR1 was increased in BRD positive animals compared to controls (P-corrected < 0.1). Cytokine expression data may help to provide insight into an animal’s health. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-018-3900-x) contains supplementary material, which is available to authorized users.",2018 Nov 3,"['Lindholm-Perry, Amanda K.', 'Kuehn, Larry A.', 'McDaneld, Tara G.', 'Miles, Jeremy R.', 'Workman, Aspen M.', 'Chitko-McKown, Carol G.', 'Keele, John W.']",BMC Res Notes,,,True
6c6622a7955d513c961a57d13a287300a8ec5c87,PMC,"Hormonal Regulation of Physiology, Innate Immunity and Antibody Response to H1N1 Influenza Virus Infection During Pregnancy",http://dx.doi.org/10.3389/fimmu.2018.02455,PMC6215819,30420854,CC BY,"In 2009, the H1N1 swine flu pandemic highlighted the vulnerability of pregnant women to influenza viral infection. Pregnant women infected with influenza A virus were at increased risk of hospitalization and severe acute respiratory distress syndrome (ARDS), which is associated with high mortality, while their newborns had an increased risk of pre-term birth or low birth weight. Pregnant women have a unique immunological profile modulated by the sex hormones required to maintain pregnancy, namely progesterone and estrogens. The role of these hormones in coordinating maternal immunotolerance in uterine tissue and cellular subsets has been well researched; however, these hormones have wide-ranging effects outside the uterus in modulating the immune response to disease. In this review, we compile research findings in the clinic and in animal models that elaborate on the unique features of H1N1 influenza A viral pathogenesis during pregnancy, the crosstalk between innate immune signaling and hormonal regulation during pregnancy, and the role of pregnancy hormones in modulating cellular responses to influenza A viral infection at mid-gestation. We highlight the ways in which lung architecture and function is stressed by pregnancy, increasing baseline inflammation prior to infection. We demonstrate that infection disrupts progesterone production and upregulates inflammatory mediators, such as cyclooxygenase-2 (COX-2) and prostaglandins, resulting in pre-term labor and spontaneous abortions. Lastly, we profile the ways in which pregnancy alters innate and adaptive cellular immune responses to H1N1 influenza viral infection, and the ways in which these protect fetal development at the expense of effective long-term immune memory. Thus, we highlight advancements in the field of reproductive immunology in response to viral infection and illustrate how that knowledge might be used to develop more effective post-infection therapies and vaccination strategies.",2018 Oct 29,"['Littauer, Elizabeth Q.', 'Skountzou, Ioanna']",Front Immunol,,,True
f6e29e95c1b0aa88f0ebebc39c62fb3bd461be2f,PMC,Molecular Distance to Health Transcriptional Score and Disease Severity in Children Hospitalized With Community-Acquired Pneumonia,http://dx.doi.org/10.3389/fcimb.2018.00382,PMC6218690,30425971,CC BY,"Background: Community-acquired pneumonia (CAP) is a leading cause of hospitalization and mortality in children. Diagnosis remains challenging and there are no reliable tools to objectively risk stratify patients or predict clinical outcomes. Molecular distance to health (MDTH) is a genomic score that measures the global perturbation of the transcriptional profile and may help classify patients by disease severity. We evaluated the value of MDTH to assess disease severity in children hospitalized with CAP. Methods: Children hospitalized with CAP and matched healthy controls were enrolled in a prospective observational study. Blood samples were obtained for transcriptome analyses within 24 h of hospitalization. MDTH scores were calculated to assess disease severity and correlated with laboratory markers, such as white blood cell count, c-reactive protein (CRP), and procalcitonin (PCT), and clinical outcomes, including duration of fever and duration of hospitalization (LOS). Univariate and multivariable logistic regression were applied to assess factors associated with LOS and duration of fever after hospitalization. Results: Among children hospitalized with CAP (n = 152), pyogenic bacteria (PB) were detected in 16 (11%), Mycoplasma pneumoniae was detected in 41 (28%), respiratory viruses (RV) alone were detected in 78 (51%), and no pathogen was detected in 17 (11%) children. Statistical group comparisons identified 6,726 genes differentially expressed in patients with CAP vs. healthy controls (n = 39). Children with confirmed PB had higher MDTH scores than those with RV (p < 0.05) or M. pneumoniae (p < 0.01) detected alone. CRP (r = 0.39, p < 0.0001), PCT (r = 0.39, p < 0.0001), and MDTHs (r = 0.24, p < 0.01) correlated with duration of fever, while only MDTHs correlated with LOS (r = 0.33, p < 0.0001). Unadjusted analyses showed that both higher CRP and MDTHs were associated with longer LOS (OR 1.04 [1–1.07] and 1.12 [1.04–1.20], respectively), however, only MDTH remained significant when adjusting for other covariates (aOR 1.11 [1.01–1.22]). Conclusions: In children hospitalized with CAP MDTH score measured within 24 h of admission was independently associated with longer duration of hospitalization, regardless of the pathogen detected. This suggests that transcriptional biomarkers may represent a promising approach to assess disease severity in children with CAP.",2018 Oct 30,"['Wallihan, Rebecca G.', 'Suárez, Nicolás M.', 'Cohen, Daniel M.', 'Marcon, Mario', 'Moore-Clingenpeel, Melissa', 'Mejias, Asuncion', 'Ramilo, Octavio']",Front Cell Infect Microbiol,,,True
af944cae16c2a0a1c705a28205da9b67a979f190,PMC,Genome-wide identification and characterization of long non-coding RNAs involved in the early somatic embryogenesis in Dimocarpus longan Lour,http://dx.doi.org/10.1186/s12864-018-5158-z,PMC6219066,30400813,CC BY,"BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in variable cleavage, transcriptional interference, regulation of DNA methylation and protein modification. However, the regulation of lncRNAs in plant somatic embryos remains unclear. The longan (Dimocarpus longan) somatic embryogenesis (SE) system is a good system for research on longan embryo development. RESULTS: In this study, 7643 lncRNAs obtained during early SE in D. longan were identified by high-throughput sequencing, among which 6005 lncRNAs were expressed. Of the expressed lncRNAs, 4790 were found in all samples and 160 were specifically expressed in embryogenic callus (EC), 154 in incomplete embryogenic compact structures (ICpECs), and 376 in globular embryos (GEs). We annotated the 6005 expressed lncRNAs, and 1404 lncRNAs belonged to 506 noncoding RNA (ncRNA) families and 4682 lncRNAs were predicted to target protein-coding genes. The target genes included 5051 cis-regulated target genes (5712 pairs) and 1605 trans-regulated target genes (3618 pairs). KEGG analysis revealed that most of the differentially expressed target genes (mRNAs) of the lncRNAs were enriched in the “plant-pathogen interaction” and “plant hormone signaling” pathways during early longan SE. Real-time quantitative PCR confirmed that 20 selected lncRNAs showed significant differences in expression and that five lncRNAs were related to auxin response factors. Compared with the FPKM expression trends, 16 lncRNA expression trends were the same in qPCR. In lncRNA-miRNA-mRNA relationship prediction, 40 lncRNAs were predicted to function as eTMs for 15 miRNAs and 7 lncRNAs were identified as potential miRNA precursors. In addition, we verified the lncRNA-miRNA-mRNA regulatory relationships by transient expression of miRNAs (miR172a, miR159a.1 and miR398a). CONCLUSION: Analyses of lncRNAs during early longan SE showed that differentially expressed lncRNAs were involved in expression regulation at each SE stage, and may form a regulatory network with miRNAs and mRNAs. These findings provide new insights into lncRNAs and lay a foundation for future functional analysis of lncRNAs during early longan SE. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-5158-z) contains supplementary material, which is available to authorized users.",2018 Nov 6,"['Chen, Yan', 'Li, Xue', 'Su, Liyao', 'Chen, Xu', 'Zhang, Shuting', 'Xu, Xiaoping', 'Zhang, Zihao', 'Chen, Yukun', 'XuHan, Xu', 'Lin, Yuling', 'Lai, Zhongxiong']",BMC Genomics,,,False
33447c36d2b2bdcc950ee40470b632e34534be7b,PMC,Genome-wide identification and characterization of long non-coding RNAs involved in the early somatic embryogenesis in Dimocarpus longan Lour,http://dx.doi.org/10.1186/s12864-018-5158-z,PMC6219066,30400813,CC BY,"BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in variable cleavage, transcriptional interference, regulation of DNA methylation and protein modification. However, the regulation of lncRNAs in plant somatic embryos remains unclear. The longan (Dimocarpus longan) somatic embryogenesis (SE) system is a good system for research on longan embryo development. RESULTS: In this study, 7643 lncRNAs obtained during early SE in D. longan were identified by high-throughput sequencing, among which 6005 lncRNAs were expressed. Of the expressed lncRNAs, 4790 were found in all samples and 160 were specifically expressed in embryogenic callus (EC), 154 in incomplete embryogenic compact structures (ICpECs), and 376 in globular embryos (GEs). We annotated the 6005 expressed lncRNAs, and 1404 lncRNAs belonged to 506 noncoding RNA (ncRNA) families and 4682 lncRNAs were predicted to target protein-coding genes. The target genes included 5051 cis-regulated target genes (5712 pairs) and 1605 trans-regulated target genes (3618 pairs). KEGG analysis revealed that most of the differentially expressed target genes (mRNAs) of the lncRNAs were enriched in the “plant-pathogen interaction” and “plant hormone signaling” pathways during early longan SE. Real-time quantitative PCR confirmed that 20 selected lncRNAs showed significant differences in expression and that five lncRNAs were related to auxin response factors. Compared with the FPKM expression trends, 16 lncRNA expression trends were the same in qPCR. In lncRNA-miRNA-mRNA relationship prediction, 40 lncRNAs were predicted to function as eTMs for 15 miRNAs and 7 lncRNAs were identified as potential miRNA precursors. In addition, we verified the lncRNA-miRNA-mRNA regulatory relationships by transient expression of miRNAs (miR172a, miR159a.1 and miR398a). CONCLUSION: Analyses of lncRNAs during early longan SE showed that differentially expressed lncRNAs were involved in expression regulation at each SE stage, and may form a regulatory network with miRNAs and mRNAs. These findings provide new insights into lncRNAs and lay a foundation for future functional analysis of lncRNAs during early longan SE. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-5158-z) contains supplementary material, which is available to authorized users.",2018 Nov 6,"['Chen, Yan', 'Li, Xue', 'Su, Liyao', 'Chen, Xu', 'Zhang, Shuting', 'Xu, Xiaoping', 'Zhang, Zihao', 'Chen, Yukun', 'XuHan, Xu', 'Lin, Yuling', 'Lai, Zhongxiong']",BMC Genomics,,,False
227045625b4e1b8b709c89f7fecf2ce1043d2ab9,PMC,Genome-wide identification and characterization of long non-coding RNAs involved in the early somatic embryogenesis in Dimocarpus longan Lour,http://dx.doi.org/10.1186/s12864-018-5158-z,PMC6219066,30400813,CC BY,"BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in variable cleavage, transcriptional interference, regulation of DNA methylation and protein modification. However, the regulation of lncRNAs in plant somatic embryos remains unclear. The longan (Dimocarpus longan) somatic embryogenesis (SE) system is a good system for research on longan embryo development. RESULTS: In this study, 7643 lncRNAs obtained during early SE in D. longan were identified by high-throughput sequencing, among which 6005 lncRNAs were expressed. Of the expressed lncRNAs, 4790 were found in all samples and 160 were specifically expressed in embryogenic callus (EC), 154 in incomplete embryogenic compact structures (ICpECs), and 376 in globular embryos (GEs). We annotated the 6005 expressed lncRNAs, and 1404 lncRNAs belonged to 506 noncoding RNA (ncRNA) families and 4682 lncRNAs were predicted to target protein-coding genes. The target genes included 5051 cis-regulated target genes (5712 pairs) and 1605 trans-regulated target genes (3618 pairs). KEGG analysis revealed that most of the differentially expressed target genes (mRNAs) of the lncRNAs were enriched in the “plant-pathogen interaction” and “plant hormone signaling” pathways during early longan SE. Real-time quantitative PCR confirmed that 20 selected lncRNAs showed significant differences in expression and that five lncRNAs were related to auxin response factors. Compared with the FPKM expression trends, 16 lncRNA expression trends were the same in qPCR. In lncRNA-miRNA-mRNA relationship prediction, 40 lncRNAs were predicted to function as eTMs for 15 miRNAs and 7 lncRNAs were identified as potential miRNA precursors. In addition, we verified the lncRNA-miRNA-mRNA regulatory relationships by transient expression of miRNAs (miR172a, miR159a.1 and miR398a). CONCLUSION: Analyses of lncRNAs during early longan SE showed that differentially expressed lncRNAs were involved in expression regulation at each SE stage, and may form a regulatory network with miRNAs and mRNAs. These findings provide new insights into lncRNAs and lay a foundation for future functional analysis of lncRNAs during early longan SE. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-5158-z) contains supplementary material, which is available to authorized users.",2018 Nov 6,"['Chen, Yan', 'Li, Xue', 'Su, Liyao', 'Chen, Xu', 'Zhang, Shuting', 'Xu, Xiaoping', 'Zhang, Zihao', 'Chen, Yukun', 'XuHan, Xu', 'Lin, Yuling', 'Lai, Zhongxiong']",BMC Genomics,,,False
ecf90eb55cfef5b0212b52caf031abb31a1f11cc,PMC,Genome-wide identification and characterization of long non-coding RNAs involved in the early somatic embryogenesis in Dimocarpus longan Lour,http://dx.doi.org/10.1186/s12864-018-5158-z,PMC6219066,30400813,CC BY,"BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in variable cleavage, transcriptional interference, regulation of DNA methylation and protein modification. However, the regulation of lncRNAs in plant somatic embryos remains unclear. The longan (Dimocarpus longan) somatic embryogenesis (SE) system is a good system for research on longan embryo development. RESULTS: In this study, 7643 lncRNAs obtained during early SE in D. longan were identified by high-throughput sequencing, among which 6005 lncRNAs were expressed. Of the expressed lncRNAs, 4790 were found in all samples and 160 were specifically expressed in embryogenic callus (EC), 154 in incomplete embryogenic compact structures (ICpECs), and 376 in globular embryos (GEs). We annotated the 6005 expressed lncRNAs, and 1404 lncRNAs belonged to 506 noncoding RNA (ncRNA) families and 4682 lncRNAs were predicted to target protein-coding genes. The target genes included 5051 cis-regulated target genes (5712 pairs) and 1605 trans-regulated target genes (3618 pairs). KEGG analysis revealed that most of the differentially expressed target genes (mRNAs) of the lncRNAs were enriched in the “plant-pathogen interaction” and “plant hormone signaling” pathways during early longan SE. Real-time quantitative PCR confirmed that 20 selected lncRNAs showed significant differences in expression and that five lncRNAs were related to auxin response factors. Compared with the FPKM expression trends, 16 lncRNA expression trends were the same in qPCR. In lncRNA-miRNA-mRNA relationship prediction, 40 lncRNAs were predicted to function as eTMs for 15 miRNAs and 7 lncRNAs were identified as potential miRNA precursors. In addition, we verified the lncRNA-miRNA-mRNA regulatory relationships by transient expression of miRNAs (miR172a, miR159a.1 and miR398a). CONCLUSION: Analyses of lncRNAs during early longan SE showed that differentially expressed lncRNAs were involved in expression regulation at each SE stage, and may form a regulatory network with miRNAs and mRNAs. These findings provide new insights into lncRNAs and lay a foundation for future functional analysis of lncRNAs during early longan SE. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-5158-z) contains supplementary material, which is available to authorized users.",2018 Nov 6,"['Chen, Yan', 'Li, Xue', 'Su, Liyao', 'Chen, Xu', 'Zhang, Shuting', 'Xu, Xiaoping', 'Zhang, Zihao', 'Chen, Yukun', 'XuHan, Xu', 'Lin, Yuling', 'Lai, Zhongxiong']",BMC Genomics,,,True
177c9a5fa045b94ea25f72ab17240cdb82585946,PMC,Promoting influenza prevention for elderly people in Hong Kong using health action process approach: study protocol,http://dx.doi.org/10.1186/s12889-018-6146-6,PMC6219178,30400790,CC BY,"BACKGROUND: People 65 years or older are at greater risk of serious complications from the seasonal influenza compared with young. To promote elderly people’s behavioral compliance toward influenza prevention, the aim of the current project is to develop, implement, and evaluate a theory-based low-administration-cost intervention building on a leading psychological theory, the Health Action Process Approach (HAPA). METHODS: The target group is Hong Kong Chinese elderly people aged 65 or older who rarely or never adopt any preventive actions. This project will be conducted in three phases over 24 months. In phase 1, intervention program will be developed building on the HAPA theoretical framework which comprises both the initiation and maintenance of influenza prevention behaviors. In phase 2, intervention will be implemented and evaluated using a randomized controlled trial, including: (a) behavior initiation only, (b) behavior initiation + behavior maintenance, and (c) control group. Both the initiation and maintenance components will comprise weekly-delivered telephone-based individual intervention sessions in 3 months. In phase 3, outcome evaluation of behavioral and psychological variables and process evaluation will be conducted. The effectiveness of the intervention will be analyzed using a series of linear mixed models on each behavioral and psychological outcome variable. Structural equation modelling will be used to test the hypothesized theoretical sequence in the HAPA model. DISCUSSION: The proposed project is expected to design theory-based intervention materials to promote the influenza prevention behaviors in Hong Kong elderly people and provide information on its effectiveness and the potential changing mechanism of behavior initiation and maintenance. TRIAL REGISTRATION: This randomized controlled trial was funded by the Health and Medical Research Fund (HMRF), Food and Health Bureau of the Government of the Hong Kong Special Administrative Region (Ref: 16151222) and was registered on 13/10/2017 at CCRB Clinical Trials Registry of the Chinese University of Hong Kong, a Partner Registry of a WHO Primary Registry (Ref: CUHK_CCRB00567).",2018 Nov 6,"['Zhang, Chun-Qing', 'Zhang, Ru', 'Chung, Pak-Kwong', 'Duan, Yanping', 'Lau, Joseph Tak fai', 'Chan, Derwin King Chung', 'Hagger, Martin S.']",BMC Public Health,,,True
9ae96559416973a6d3bb6ddd5d446bfb4aaf40a0,PMC,The effects of in ovo administration of encapsulated Toll-like receptor 21 ligand as an adjuvant with Marek’s disease vaccine,http://dx.doi.org/10.1038/s41598-018-34760-6,PMC6219601,30401976,CC BY,"Marek’s Disease Virus (MDV) is the causative agent of a lymphoproliferative disease, Marek’s disease (MD) in chickens. MD is only controlled by mass vaccination; however, immunity induced by MD vaccines is unable to prevent MDV replication and transmission. The herpesvirus of turkey (HVT) vaccine is one of the most widely used MD vaccines in poultry industry. Vaccines can be adjuvanted with Toll-like receptor ligands (TLR-Ls) to enhance their efficacy. In this study, we examined whether combining TLR-Ls with HVT can boost host immunity against MD and improve its efficacy. Results demonstrated that HVT alone or HVT combined with encapsulated CpG-ODN partially protected chickens from tumor incidence and reduced virus replication compared to the control group. However, encapsulated CpG-ODN only moderately, but not significantly, improved HVT efficacy and reduced tumor incidence from 53% to 33%. Further investigation of cytokine gene profiles in spleen and bursa of Fabricius revealed an inverse association between interleukin (IL)-10 and IL-18 expression and protection conferred by different treatments. In addition, the results of this study raise the possibility that interferon (IFN)-β and IFN-γ induced by the treatments may exert anti-viral responses against MDV replication in the bursa of Fabricius at early stage of MDV infection in chickens.",2018 Nov 6,"['Bavananthasivam, Jegarubee', 'Read, Leah', 'Astill, Jake', 'Yitbarek, Alexander', 'Alkie, Tamiru N.', 'Abdul-Careem, Mohamed Faizal', 'Wootton, Sarah K.', 'Behboudi, Shahriar', 'Sharif, Shayan']",Sci Rep,,,True
3422bab59932dcb046a0dfe931eb71173130979f,PMC,Closed-type pre-treatment device for point-of-care testing of sputum,http://dx.doi.org/10.1038/s41598-018-34781-1,PMC6220321,30405199,CC BY,"The procedures and protocols for the pre-treatment of sputum specimens, mainly used for the diagnosis of pneumonia, are complex, labor intensive, and require skilled specialists working in a biosafety containment laboratory because of sample infectivity. In this study, we developed the first portable, low-power pre-treatment device that carries out all sputum pre-treatment procedures (liquefaction, homogenization, dissolution, and inactivation) in an enclosed space. Designed to simultaneously employ chemical and mechanical dissolution in the enclosed chamber, this device eliminates the risk of transmission and improves the effectiveness of sputum dissolution and pathogen detection. This device is expected to allow for the pre-treatment of infectious sputum specimens outside of a biosafety containment laboratory. Used in conjunction with automated genome extraction and detection systems, this device should make the on-site diagnosis using infectious sputum specimens possible.",2018 Nov 7,"['Park, Hyun-Ju', 'Woo, Ayoung', 'Cha, Jae Min', 'Lee, Kyu-Sung', 'Lee, Min-Young']",Sci Rep,,,True
d6f1c9865c7d63536a77b8ba4e9bad1b507f9eb6,PMC,Hyponatremia in children with respiratory infections: a cross-sectional analysis of a cohort of 3938 patients,http://dx.doi.org/10.1038/s41598-018-34703-1,PMC6220324,30405154,CC BY,"Hyponatremia can be a life-threatening illness among hospitalized children. The aims of this study were to evaluate the incidence and risk factors of hyponatremia in 3938 children who were admitted to the Cheil General Hospital and Women’s Health Care Center with respiratory infections. Clinical data were collected, and multiplex RT-PCR analyses were done for various microorganisms. Hyponatremia was observed in 531 (13.5%) patients. The incidence of hyponatremia differed according to the respiratory tract infection (P < 0.0001) and microorganism (P = 0.001). In children with hyponatremia, the age at admission was significantly older (P < 0.0001), male gender was more frequent (P = 0.019), CRP was higher (P < 0.0001), and coinfection with multiple organisms was more common (P = 0.001) than in children without hyponatremia. In multivariate analyses, an older age at admission (P = 0.006), male gender (P = 0.004), and increased CRP (P < 0.0001) were independent risk factors. Sodium levels correlated negatively with WBC (P = 0.037), CRP (P < 0.0001), and number of hospital days (P = 0.020). The AUC values of age (0.586, P < 0.0001), CRP (0.599, P < 0.0001), and blood urea nitrogen (0.559, P < 0.0001) were all significant predictors of hyponatremia. This study is the first to show that the incidence of hyponatremia differs according to infecting microorganism and radiological findings.",2018 Nov 7,"['Park, Sung Won', 'Shin, Son Moon', 'Jeong, Moonsun', 'Cho, Dong-Hee', 'Lee, Keum Hwa', 'Eisenhut, Michael', 'Kronbichler, Andreas', 'Moritz, Michael', 'Il Shin, Jae']",Sci Rep,,,True
d9622ec04bc88f584cd280c9dccd177066960cf0,PMC,Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence,http://dx.doi.org/10.1093/ve/vey033,PMC6220371,30425841,CC BY,"Molecular phylogenetics is often used to estimate the time since the divergence of modern gene sequences. For highly diverged sequences, such phylogenetic techniques sometimes estimate surprisingly recent divergence times. In the case of viruses, independent evidence indicates that the estimates of deep divergence times from molecular phylogenetics are sometimes too recent. This discrepancy is caused in part by inadequate models of purifying selection leading to branch-length underestimation. Here we examine the effect on branch-length estimation of using models that incorporate experimental measurements of purifying selection. We find that models informed by experimentally measured site-specific amino-acid preferences estimate longer deep branches on phylogenies of influenza virus hemagglutinin. This lengthening of branches is due to more realistic stationary states of the models, and is mostly independent of the branch-length extension from modeling site-to-site variation in amino-acid substitution rate. The branch-length extension from experimentally informed site-specific models is similar to that achieved by other approaches that allow the stationary state to vary across sites. However, the improvements from all of these site-specific but time homogeneous and site independent models are limited by the fact that a protein’s amino-acid preferences gradually shift as it evolves. Overall, our work underscores the importance of modeling site-specific amino-acid preferences when estimating deep divergence times—but also shows the inherent limitations of approaches that fail to account for how these preferences shift over time.",2018 Nov 6,"['Hilton, Sarah K', 'Bloom, Jesse D']",Virus Evol,,,True
c54a28ed68b1d30d44a3bce4033fa3e74103a33b,PMC,The Fourth International Neonatal and Maternal Immunization Symposium (INMIS 2017): Toward Integrating Maternal and Infant Immunization Programs,http://dx.doi.org/10.1128/mSphere.00221-18,PMC6222055,30404933,CC BY,"Prevention of serious infections in pregnant mothers, newborns, and young infants through immunization during pregnancy and in early life has the potential to further reduce maternal and neonatal morbidity and mortality worldwide. In the past decade, research in this field has advanced substantially, from the understanding of the biology and immunology of pregnancy and early life, to the active development of several candidate vaccines, for which challenges and opportunities for global implementation are under consideration. Experts from academia, industry, regulatory and funding agencies, public health, and international organizations met in Brussels (Belgium) from 10 to 12 September 2017, at the 4th International Neonatal and Maternal Immunization Symposium (INMIS), to review the most relevant advances in maternal and neonatal immunization. The overarching focus of the conference was to identify the path forward to achieve integration of maternal and early life immunization strategies for the successful implementation of vaccines in antenatal care and pediatric programs for reduction of maternal and infant mortality worldwide. IMPORTANCE This report provides an overview of the proceedings of the 4th International Maternal and Neonatal Immunization Symposium, where presentations focused on the state-of-the-art research on the development and implementation of vaccines given during pregnancy for the protection of mothers and infants.",2018 Nov 7,"['Munoz, Flor M.', 'Van Damme, Pierre', 'Dinleyici, Ener', 'Clarke, Ed', 'Kampmann, Beate', 'Heath, Paul T.', 'Levy, Ofer', 'Leuridan, Elke', 'Cutland, Clare', 'Sobanjo-ter Meulen, Ajoke', 'Marchant, Arnaud']",mSphere,,,True
c85ca5217f9051f83911569eed1eb52cf992f7dd,PMC,Computational Molecular Docking and X-ray Crystallographic Studies of Catechins in New Drug Design Strategies,http://dx.doi.org/10.3390/molecules23082020,PMC6222539,30104534,CC BY,"Epidemiological and laboratory studies have shown that green tea and green tea catechins exert beneficial effects on a variety of diseases, including cancer, metabolic syndrome, infectious diseases, and neurodegenerative diseases. In most cases, (−)-epigallocatechin gallate (EGCG) has been shown to play a central role in these effects by green tea. Catechins from other plant sources have also shown health benefits. Many studies have revealed that the binding of EGCG and other catechins to proteins is involved in its action mechanism. Computational docking analysis (CMDA) and X-ray crystallographic analysis (XCA) have provided detailed information on catechin-protein interactions. Several of these studies have revealed that the galloyl moiety anchors it to the cleft of proteins through interactions with its hydroxyl groups, explaining the higher activity of galloylated catechins such as EGCG and epicatechin gallate than non-galloylated catechins. In this paper, we review the results of CMDA and XCA of EGCG and other plant catechins to understand catechin-protein interactions with the expectation of developing new drugs with health-promoting properties.",2018 Aug 13,"['Nakano, Shogo', 'Megro, Shin-ichi', 'Hase, Tadashi', 'Suzuki, Takuji', 'Isemura, Mamoru', 'Nakamura, Yoriyuki', 'Ito, Sohei']",Molecules,,,True
ac0a277a70cf2e3e6e51ddb07ad06eae08cc7fef,PMC,"Isoxazolidine Conjugates of N3-Substituted 6-Bromoquinazolinones—Synthesis, Anti-Varizella-Zoster Virus, and Anti-Cytomegalovirus Activity",http://dx.doi.org/10.3390/molecules23081889,PMC6222691,30060562,CC BY,"1,3-Dipolar cycloaddition of N-methyl C-(diethoxyphosphoryl) nitrone to N3-substituted 6-bromo-2-vinyl-3H-quinazolin-4-ones gave (3-diethoxyphosphoryl) isoxazolidines substituted at C5 with quinazolinones modified at N3. All isoxazolidine cycloadducts were screened for antiviral activity against a broad spectrum of DNA and RNA viruses. Several isoxazolidines inhibited the replication of both thymidine kinase wild-type and deficient (TK(+) and TK(−)) varicella-zoster virus strains at EC(50) in the 5.4–13.6 μΜ range, as well as human cytomegalovirus (EC(50) = 8.9–12.5 μΜ). Isoxazolidines trans-11b, trans-11c, trans-11e, trans-11f/cis-11f, trans-11g, trans-11h, and trans-11i/cis-11i exhibited moderate cytostatic activity towards the human lymphocyte cell line CEM (IC(50) = 9.6–17 μM).",2018 Jul 28,"['Grabkowska-Drużyc, Magdalena', 'Andrei, Graciela', 'Schols, Dominique', 'Snoeck, Robert', 'Piotrowska, Dorota G.']",Molecules,,,True
c2fa41c3b09393428d9f973feb22bee011015eee,PMC,Aminobenzosuberone Scaffold as a Modular Chemical Tool for the Inhibition of Therapeutically Relevant M1 Aminopeptidases,http://dx.doi.org/10.3390/molecules23102607,PMC6222927,30314342,CC BY,"The synthesis of racemic substituted 7-amino-5,7,8,9-tetrahydrobenzocyclohepten-6-one hydrochlorides was optimized to enhance reproducibility and increase the overall yield. In order to investigate their specificity, series of enzyme inhibition assays were carried out against a diversity of proteases, covering representative members of aspartic, cysteine, metallo and serine endopeptidases and including eight members of the monometallic M1 family of aminopeptidases as well as two members of the bimetallic M17 and M28 aminopeptidase families. This aminobenzosuberone scaffold indeed demonstrated selective inhibition of M1 aminopeptidases to the exclusion of other tested protease families; it was particularly potent against mammalian APN and its bacterial/parasitic orthologues EcPepN and PfAM1.",2018 Oct 11,"['Salomon, Emmanuel', 'Schmitt, Marjorie', 'Marapaka, Anil Kumar', 'Stamogiannos, Athanasios', 'Revelant, Germain', 'Schmitt, Céline', 'Alavi, Sarah', 'Florent, Isabelle', 'Addlagatta, Anthony', 'Stratikos, Efstratios', 'Tarnus, Céline', 'Albrecht, Sébastien']",Molecules,,,True
d33f858e29256297e9721a300f968f346aa81b0b,PMC,Aminobenzosuberone Scaffold as a Modular Chemical Tool for the Inhibition of Therapeutically Relevant M1 Aminopeptidases,http://dx.doi.org/10.3390/molecules23102607,PMC6222927,30314342,CC BY,"The synthesis of racemic substituted 7-amino-5,7,8,9-tetrahydrobenzocyclohepten-6-one hydrochlorides was optimized to enhance reproducibility and increase the overall yield. In order to investigate their specificity, series of enzyme inhibition assays were carried out against a diversity of proteases, covering representative members of aspartic, cysteine, metallo and serine endopeptidases and including eight members of the monometallic M1 family of aminopeptidases as well as two members of the bimetallic M17 and M28 aminopeptidase families. This aminobenzosuberone scaffold indeed demonstrated selective inhibition of M1 aminopeptidases to the exclusion of other tested protease families; it was particularly potent against mammalian APN and its bacterial/parasitic orthologues EcPepN and PfAM1.",2018 Oct 11,"['Salomon, Emmanuel', 'Schmitt, Marjorie', 'Marapaka, Anil Kumar', 'Stamogiannos, Athanasios', 'Revelant, Germain', 'Schmitt, Céline', 'Alavi, Sarah', 'Florent, Isabelle', 'Addlagatta, Anthony', 'Stratikos, Efstratios', 'Tarnus, Céline', 'Albrecht, Sébastien']",Molecules,,,True
c856a5583dad88feeb274cf1ba74ce99632d3d6c,PMC,Porcine epidemic diarrhea virus S1 protein is the critical inducer of apoptosis,http://dx.doi.org/10.1186/s12985-018-1078-4,PMC6222994,30404647,CC BY,"BACKGROUND: Porcine Epidemic Diarrhea (PED) is an acute and highly contagious enteric disease caused by PED virus (PEDV), characterized by vomitting, watery diarrhea and fatal dehydration with high mortality in sucking piglets of one week of age. Although PEDV induced cell apoptosis has been established in vitro and in vivo, the functional protein that contributes to this event remains unclear. METHODS: The activation or cleavage of main apoptosis-associated molecular such as AIFM1, caspase-3, caspase-8, caspase-9 and PARP in PEDV infected host cells were analyzed by western blotting. The nuclear change of infected cell was monitored by confocal immunofluorescence assay. The overexpressing plasmids of 16 non-structural proteins (Nsp1–16) and 6 structural proteins (M, N, E, ORF3, S1 and S2) were constructed by cloning. Cell apoptosis induced by PEDV or overexpression non-structural or structural proteins was measured by the flow cytometry assay. RESULTS: PEDV could infect various host cells including Vero, Vero-E6 and Marc-145 and cause obvious cytopathic effects, including roundup, cell fusion, cell membrane vacuolation, syncytium formation and cause apparent apoptosis. In infected cells, PEDV-induced apoptosis is accompanied by nuclear concentration and fragmentation as a result of caspase-3 and caspase-8 activation and AIFM1 and PARP cleavage. Overexpression of S1 Spike protein of PEDV SM98 strain effectively induced host cell apoptosis, while the expression of the other non-structure proteins (Nsp1–16) and structural proteins (M, N, E, S2 and ORF3) has no or less effect on cell apoptosis. Similarly, expression of S1 protein from wild-type strain BJ2011 or cell-adapted strain CV777, also induce apoptosis in transfected cells. Finally, we demonstrated that the S1 proteins from various coronavirus family members such as TGEV, IBV, CCoV, SARS and MERS could also induce Vero-E6 cells apoptosis. CONCLUSION: S1 Spike protein is one of the most critical functional proteins that contribute to cell apoptosis. Expression of S1 proteins of the coronavirus tested in this study could all induce cell apoptosis suggesting S1 maybe is an effective inducer in Coronavirus-induced cell apoptosis and targeting S1 protein expression probably is a promising strategy to inhibit coronavirus infection and thus mediated apoptosis on host cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1078-4) contains supplementary material, which is available to authorized users.",2018 Nov 7,"['Chen, Yifeng', 'Zhang, Zhibang', 'Li, Jie', 'Gao, Yueyi', 'Zhou, Lei', 'Ge, Xinna', 'Han, Jun', 'Guo, Xin', 'Yang, Hanchun']",Virol J,,,True
729748c83fe9f501d28aae521d7528ec33d0c7ee,PMC,Helium-oxygen mixture: clinical applicability in an intensive care unit,http://dx.doi.org/10.31744/einstein_journal/2018AO4199,PMC6223943,30427479,CC BY,"OBJECTIVE: To evaluate if distress respiratory decreases after using helium-oxygen mixture in pediatric patients diagnosed with bronchospasm. METHODS: This is a retrospective, non-randomized study that included patients diagnosed with bronchospasm, who received a helium-oxygen mixture at three time points (30, 60, and 120 minutes) according to the organization protocol singular, and were admitted to the intensive care unit, from January 2012 to December 2013. This protocol includes patients with bronchospasm who sustained a modified Wood score of moderate to severe, even after one hour of conventional treatment. RESULTS: Twenty children were included in the study. The mean score of severity of the disease at the initial moment was 5.6 (SD:2.0), and at moment 120 minutes, it was 3.4 (SD: 2.0). The severity score showed a significant improvement as of 30 minutes (p<0.001). CONCLUSION: The use of helium-oxygen mixture proved to be effective in diminishing the respiratory distress score for children with airway obstructions; it should be considered a supplementary therapeutic option, together with drug therapy, in specific clinical situations.",2018 Oct 30,"['Nascimento, Milena Siciliano', 'Santos, Érica', 'do Prado, Cristiane']",Einstein (Sao Paulo),,,True
dc173bac1ccb553dddf68b82320dfae5ff306f28,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,True
c7cd6b41d8526f865821abc06fc4bb17923f16f0,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,True
39f1634046dffbbb7da9f5ef69fa08bdb7b7096f,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,True
aebe62afbcca5c6f4671cfe8763dd24c3eec3b3f,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
aa018462fb01cd06ebe5bbc4400c3e7555273f16,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
68c801d5d86cadbbcb8b111df6b2a74fee2ddddc,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
f3e5cde42f4770639ad39a2a3dff2cef0559ddca,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
08009b4d80bd7c741cd7c6ca736b1d2347045b6e,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
2e0b69d338fec7a243a0b2c02a7f2a9722e07054,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,True
ebc8949731f5cd59084c4733eb4211d83547e4e8,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
ef4f719d51fae2af844e08b3f55c2566ccc8f970,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
855674634890e8e2e9d575830b27ac23c6d82ac6,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
26a8fbc315b68df78e22f4d41f5104903de96722,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
535f12b7503fbb5430161db1ad6ab6f90f0c1973,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
ebf447e0e1957815cb8cf130a84ed2bde14bacda,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,True
aa22e7ec1d34b8be4da7d3d6a3e7e9db9d8fe4fa,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
9afcc1b80d73bef34eb59f84f1245b6792fb0d89,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
f32dfc274f24d8baf16b2a8e0084396b7a303494,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
3b1c5eb21d8e235d526814f8f6b5d3a1a3831a4a,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
b475438a09acce47100210534c623e75f3b5bcc2,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
d7bbd4fae42f87216f5125b11b99059307bdeb7a,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
1a0cfa0ea0f0dd1d80e9bbc0d0a7624a8e6b00f8,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
5061cc34928ee9d6964e231a10b5b3feb28921c6,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
984fcfde5876461ab125c70b9ac84fd3c14ed253,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
a24fde550c2ffb50af8b246ec95b5e2974f709ea,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
10252a7b7733f29a51c9fd89898426177d732827,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
190ffaedada9b387fb9c9f7923121d0bc894e317,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
a7089c46e8de5bff872fa4b35d5101d33a4df325,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
5f9264180994f95d99b032870ab72fa5705c6fc9,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
a63fa590ced98eeb69632fc730b73e5f501a3828,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
a137870341c8a34855b4f937db6cc6d8795f0b43,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
452932e0304576e8e041581e78e1ab1dee731e93,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
318a86d53139d19c8c4b7e875a31df7ba38ba5c3,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
09fc6bb47a999db23105595d1718dc3ac9a37653,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
cc14821eb2837ba5833f0ddc5ab32b8f39025f62,PMC,A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs),http://dx.doi.org/10.1371/journal.pcbi.1006483,PMC6224041,30408032,CC BY,"The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.",2018 Nov 8,"['Ehrt, Christiane', 'Brinkjost, Tobias', 'Koch, Oliver']",PLoS Comput Biol,,,False
fb6da430431e830785d08a54b099e711fabe252e,PMC,The calendar of epidemics: Seasonal cycles of infectious diseases,http://dx.doi.org/10.1371/journal.ppat.1007327,PMC6224126,30408114,CC BY,,2018 Nov 8,"Martinez, Micaela Elvira",PLoS Pathog,,,True
ceba28d8304f3df8001164f8edeef545154289f6,PMC,CD4 T cells control development and maintenance of brain-resident CD8 T cells during polyomavirus infection,http://dx.doi.org/10.1371/journal.ppat.1007365,PMC6224182,30372487,CC BY,"Tissue-resident memory CD8 T (T(RM)) cells defend against microbial reinfections at mucosal barriers; determinants driving durable T(RM) cell responses in non-mucosal tissues, which often harbor opportunistic persistent pathogens, are unknown. JC polyomavirus (JCPyV) is a ubiquitous constituent of the human virome. With altered immunological status, JCPyV can cause the oft-fatal brain demyelinating disease progressive multifocal leukoencephalopathy (PML). JCPyV is a human-only pathogen. Using the mouse polyomavirus (MuPyV) encephalitis model, we demonstrate that CD4 T cells regulate development of functional antiviral brain-resident CD8 T cells (bT(RM)) and renders their maintenance refractory to systemic CD8 T cell depletion. Acquired CD4 T cell deficiency, modeled by delaying systemic CD4 T cell depletion until MuPyV-specific CD8 T cells have infiltrated the brain, impacted the stability of CD8 bT(RM), impaired their effector response to reinfection, and rendered their maintenance dependent on circulating CD8 T cells. This dependence of CD8 bT(RM) differentiation on CD4 T cells was found to extend to encephalitis caused by vesicular stomatitis virus. Together, these findings reveal an intimate association between CD4 T cells and homeostasis of functional bT(RM) to CNS viral infection.",2018 Oct 29,"['Mockus, Taryn E.', 'Shwetank,', 'Lauver, Matthew D.', 'Ren, Heather M.', 'Netherby, Colleen S.', 'Salameh, Tarik', 'Kawasawa, Yuka Imamura', 'Yue, Feng', 'Broach, James R.', 'Lukacher, Aron E.']",PLoS Pathog,,,True
3727230a23a43b18086004127d3d288db1ba3bf5,PMC,A Comprehensive In Silico Method to Study the QSTR of the Aconitine Alkaloids for Designing Novel Drugs,http://dx.doi.org/10.3390/molecules23092385,PMC6225272,30231506,CC BY,"A combined in silico method was developed to predict potential protein targets that are involved in cardiotoxicity induced by aconitine alkaloids and to study the quantitative structure–toxicity relationship (QSTR) of these compounds. For the prediction research, a Protein-Protein Interaction (PPI) network was built from the extraction of useful information about protein interactions connected with aconitine cardiotoxicity, based on nearly a decade of literature and the STRING database. The software Cytoscape and the PharmMapper server were utilized to screen for essential proteins in the constructed network. The Calcium-Calmodulin-Dependent Protein Kinase II alpha (CAMK2A) and gamma (CAMK2G) were identified as potential targets. To obtain a deeper insight on the relationship between the toxicity and the structure of aconitine alkaloids, the present study utilized QSAR models built in Sybyl software that possess internal robustness and external high predictions. The molecular dynamics simulation carried out here have demonstrated that aconitine alkaloids possess binding stability for the receptor CAMK2G. In conclusion, this comprehensive method will serve as a tool for following a structural modification of the aconitine alkaloids and lead to a better insight into the cardiotoxicity induced by the compounds that have similar structures to its derivatives.",2018 Sep 18,"['Wang, Ming-Yang', 'Liang, Jing-Wei', 'Mohamed Olounfeh, Kamara', 'Sun, Qi', 'Zhao, Nan', 'Meng, Fan-Hao']",Molecules,,,True
3d19858c100bda219ded8c1dd388c0e7f730ac02,PMC,Experimental screening studies on rabies virus transmission and oral rabies vaccination of the Greater Kudu (Tragelaphus strepsiceros),http://dx.doi.org/10.1038/s41598-018-34985-5,PMC6226427,30413745,CC BY,"Rabies in the Greater Kudu (Tragelaphus strepsiceros) in Namibia is unique and found in such magnitude as has not been reported elsewhere in southern Africa. Reasons as to why Kudus appear to be exceptionally susceptible to rabies still remain speculative at best. Because the current severe rabies endemic in Kudus continues to have an enormous negative impact on the Namibian agricultural sector, we set out to question existing dogmas regarding the epidemiology of the disease in a unique experimental setting. In addition, we explored effective measures to protect these antelopes. Although we were able to confirm high susceptibly of kudus for rabies and sporadic horizontal rabies virus transmission to contact animals, we contend that these observations cannot plausibly explain the rapid spread of the disease in Kudus over large territories. Since parenteral vaccination of free-roaming Kudus is virtually impossible, oral rabies vaccination using modified life virus vaccines with a high safety profile would be the ultimate solution to the problem. In a proof-of-concept study using a 3rd generation oral rabies virus vaccine construct (SPBN GASGAS) we found evidence that Kudus can be vaccinated by the oral route and protected against a subsequent rabies infection. In a second phase, more targeted studies need to be initiated by focusing on optimizing oral vaccine uptake and delivery.",2018 Nov 9,"['Hassel, Rainer', 'Vos, Ad', 'Clausen, Peter', 'Moore, Susan', 'van der Westhuizen, Jolandie', 'Khaiseb, Siegfried', 'Kabajani, Juliet', 'Pfaff, Florian', 'Höper, Dirk', 'Hundt, Boris', 'Jago, Mark', 'Bruwer, Floris', 'Lindeque, Pauline', 'Finke, Stefan', 'Freuling, Conrad M.', 'Müller, Thomas']",Sci Rep,,,False
31d093e41e871ccc4472ec4bcfccb4a94a46653e,PMC,Experimental screening studies on rabies virus transmission and oral rabies vaccination of the Greater Kudu (Tragelaphus strepsiceros),http://dx.doi.org/10.1038/s41598-018-34985-5,PMC6226427,30413745,CC BY,"Rabies in the Greater Kudu (Tragelaphus strepsiceros) in Namibia is unique and found in such magnitude as has not been reported elsewhere in southern Africa. Reasons as to why Kudus appear to be exceptionally susceptible to rabies still remain speculative at best. Because the current severe rabies endemic in Kudus continues to have an enormous negative impact on the Namibian agricultural sector, we set out to question existing dogmas regarding the epidemiology of the disease in a unique experimental setting. In addition, we explored effective measures to protect these antelopes. Although we were able to confirm high susceptibly of kudus for rabies and sporadic horizontal rabies virus transmission to contact animals, we contend that these observations cannot plausibly explain the rapid spread of the disease in Kudus over large territories. Since parenteral vaccination of free-roaming Kudus is virtually impossible, oral rabies vaccination using modified life virus vaccines with a high safety profile would be the ultimate solution to the problem. In a proof-of-concept study using a 3rd generation oral rabies virus vaccine construct (SPBN GASGAS) we found evidence that Kudus can be vaccinated by the oral route and protected against a subsequent rabies infection. In a second phase, more targeted studies need to be initiated by focusing on optimizing oral vaccine uptake and delivery.",2018 Nov 9,"['Hassel, Rainer', 'Vos, Ad', 'Clausen, Peter', 'Moore, Susan', 'van der Westhuizen, Jolandie', 'Khaiseb, Siegfried', 'Kabajani, Juliet', 'Pfaff, Florian', 'Höper, Dirk', 'Hundt, Boris', 'Jago, Mark', 'Bruwer, Floris', 'Lindeque, Pauline', 'Finke, Stefan', 'Freuling, Conrad M.', 'Müller, Thomas']",Sci Rep,,,True
1185137c3c9ddbc0c91aa718179dadd11039f771,PMC,Functional analysis of potential cleavage sites in the MERS-coronavirus spike protein,http://dx.doi.org/10.1038/s41598-018-34859-w,PMC6226446,30413791,CC BY,"The Middle East respiratory syndrome-related coronavirus (MERS-CoV) can cause severe disease and has pandemic potential. Therefore, development of antiviral strategies is an important task. The activation of the viral spike protein (S) by host cell proteases is essential for viral infectivity and the responsible enzymes are potential therapeutic targets. The cellular proteases furin, cathepsin L and TMPRSS2 can activate MERS-S and may cleave the S protein at two distinct sites, termed S1/S2 and S2′. Moreover, a potential cathepsin L cleavage site in MERS-S has been reported. However, the relative importance of these sites for MERS-S activation is incompletely understood. Here, we used mutagenic analysis and MERS-S-bearing vectors to study the contribution of specific cleavage sites to S protein-driven entry. We found that an intact S1/S2 site was only required for efficient entry into cells expressing endogenous TMPRSS2. In keeping with a previous study, pre-cleavage at the S1/S2 motif (RSVR) was important although not essential for subsequent MERS-S activation by TMPRSS2, and indirect evidence was obtained that this motif is processed by a protease depending on an intact RXXR motif, most likely furin. In contrast, the S2′ site (RSAR) was required for robust viral entry into all cell lines tested and the integrity of one of the two arginines was sufficient for efficient entry. These findings suggest that cleavage at S2′ is carried out by proteases recognizing a single arginine, most likely TMPRSS2 and cathepsin L. Finally, mutation of the proposed cathepsin L site did not impact viral entry and double mutation of S1/S2 and S2′ site was compatible with cathepsin L- but not TMPRSS2-dependent host cell entry, indicating that cathepsin L can process the S protein at auxiliary sites. Collectively, our results indicate a rigid sequence requirement for S protein activation by TMPRSS2 but not cathepsin L.",2018 Nov 9,"['Kleine-Weber, Hannah', 'Elzayat, Mahmoud Tarek', 'Hoffmann, Markus', 'Pöhlmann, Stefan']",Sci Rep,,,True
5791f66122a1e6d2af0b23f5722eea330552c32b,PMC,Transcriptomics in lung tissue upon respiratory syncytial virus infection reveals aging as important modulator of immune activation and matrix maintenance,http://dx.doi.org/10.1038/s41598-018-35180-2,PMC6226529,30413794,CC BY,"Aging poses an increased risk of severe infection by respiratory syncytial virus (RSV). The many different biological pathways comprising the response to infection in lungs that are influenced by aging are complex and remain to be defined more thoroughly. Towards finding new directions in research on aging, we aimed to define biological pathways in the acute response to RSV that are affected in the lungs by aging. We therefore profiled the full transcriptome of lung tissue of mice prior to and during RSV infection both at young and old age. In the absence of RSV, we found aging to downregulate genes that are involved in constitution of the extracellular matrix. Moreover, uninfected old mice showed elevated expression of pathways that resemble injury, metabolic aberrations, and disorders mediated by functions of the immune system that were induced at young age only by an exogenous trigger like RSV. Furthermore, infection by RSV mounted stronger activation of anti-viral type-I interferon pathways at old age. Despite such exaggerated anti-viral responses, old mice showed reduced control of virus. Altogether, our findings emphasize important roles in aging-related susceptibility to respiratory disease for extracellular matrix dysfunctions and dysregulated immune activation in lungs.",2018 Nov 9,"['Pennings, Jeroen L. A.', 'Mariman, Rob', 'Hodemaekers, Hennie M.', 'Reemers, Sylvia S. N.', 'Janssen, Riny', 'Guichelaar, Teun']",Sci Rep,,,False
f18b80a866dfde9b2c219a73f3721237a8da5063,PMC,Transcriptomics in lung tissue upon respiratory syncytial virus infection reveals aging as important modulator of immune activation and matrix maintenance,http://dx.doi.org/10.1038/s41598-018-35180-2,PMC6226529,30413794,CC BY,"Aging poses an increased risk of severe infection by respiratory syncytial virus (RSV). The many different biological pathways comprising the response to infection in lungs that are influenced by aging are complex and remain to be defined more thoroughly. Towards finding new directions in research on aging, we aimed to define biological pathways in the acute response to RSV that are affected in the lungs by aging. We therefore profiled the full transcriptome of lung tissue of mice prior to and during RSV infection both at young and old age. In the absence of RSV, we found aging to downregulate genes that are involved in constitution of the extracellular matrix. Moreover, uninfected old mice showed elevated expression of pathways that resemble injury, metabolic aberrations, and disorders mediated by functions of the immune system that were induced at young age only by an exogenous trigger like RSV. Furthermore, infection by RSV mounted stronger activation of anti-viral type-I interferon pathways at old age. Despite such exaggerated anti-viral responses, old mice showed reduced control of virus. Altogether, our findings emphasize important roles in aging-related susceptibility to respiratory disease for extracellular matrix dysfunctions and dysregulated immune activation in lungs.",2018 Nov 9,"['Pennings, Jeroen L. A.', 'Mariman, Rob', 'Hodemaekers, Hennie M.', 'Reemers, Sylvia S. N.', 'Janssen, Riny', 'Guichelaar, Teun']",Sci Rep,,,True
34c5a299626d47493cf1bd35b16debc3f12ca798,PMC,Etiology of Coinfections in Children with Influenza during 2015/16 Winter Season in Nepal,http://dx.doi.org/10.1155/2018/8945142,PMC6230385,30510579,CC BY,"Acute respiratory infections (ARIs) are one of the major public health problems in developing countries like Nepal. Besides the influenza, several other pathogens are responsible for acute respiratory infection in children. Etiology of infections is poorly characterized at the course of clinical management, and hence empirical antimicrobial agents are used. The objective of this study was to characterize the influenza and other respiratory pathogens by real-time PCR assay. A total of 175 throat swab specimens of influenza-positive cases collected at National Influenza Center, Nepal, during the 2015/16 winter season were selected for detecting other respiratory copathogens. Total nucleic acid was extracted using Pure Link viral RNA/DNA mini kit (Invitrogen), and multiplex RT-PCR assays were performed. Influenza A and B viruses were found in 120 (68.6%) and 55 (31.4%) specimens, respectively, among which coinfections were found in 106 (60.6%) specimens. Among the influenza A-positive cases, 25 (20.8%) were A/H1N1 pdm09 and 95 (79.2%) were A/H3 subtypes. Viruses coinfected frequently with influenza virus in children were rhinovirus (26; 14.8%), respiratory syncytial virus A/B (19; 10.8%), adenovirus (14; 8.0%), coronavirus (CoV)-HKU1 (14; 8.0%), CoV-OC43 (5; 2.9%), CoV-229E (2; 1.1%), metapneumovirus A/B (5; 2.9%), bocavirus (6; 3.4%), enterovirus (5; 2.9%), parainfluenza virus-1 (3; 1.7%), and parainfluenza virus-3 (2; 1.1%). Coinfection of Mycoplasma pneumoniae with influenza virus was found in children (5; 2.8%). Most of the viral infection occurred in young children below 5 years of age. In addition to influenza virus, nine different respiratory pathogens were detected, of which coinfections of rhinovirus and respiratory syncytial virus A/B were predominantly found in children. This study gives us better information on the respiratory pathogen profile and coinfection combinations which are important for diagnosis and treatment of ARIs.",2018 Oct 28,"['Upadhyay, Bishnu Prasad', 'Banjara, Megha Raj', 'Shrestha, Ram Krishna', 'Tashiro, Masato', 'Ghimire, Prakash']",Int J Microbiol,,,True
1d2a06d34c1ae369008931acca5000233e246011,PMC,The Interplay Between Immune Response and Bacterial Infection in COPD: Focus Upon Non-typeable Haemophilus influenzae,http://dx.doi.org/10.3389/fimmu.2018.02530,PMC6230626,30455693,CC BY,"Chronic obstructive pulmonary disease (COPD) is a debilitating respiratory disease and one of the leading causes of morbidity and mortality worldwide. It is characterized by persistent respiratory symptoms and airflow limitation due to abnormalities in the lower airway following consistent exposure to noxious particles or gases. Acute exacerbations of COPD (AECOPD) are characterized by increased cough, purulent sputum production, and dyspnea. The AECOPD is mostly associated with infection caused by common cold viruses or bacteria, or co-infections. Chronic and persistent infection by non-typeable Haemophilus influenzae (NTHi), a Gram-negative coccobacillus, contributes to almost half of the infective exacerbations caused by bacteria. This is supported by reports that NTHi is commonly isolated in the sputum from COPD patients during exacerbations. Persistent colonization of NTHi in the lower airway requires a plethora of phenotypic adaptation and virulent mechanisms that are developed over time to cope with changing environmental pressures in the airway such as host immuno-inflammatory response. Chronic inhalation of noxious irritants in COPD causes a changed balance in the lung microbiome, abnormal inflammatory response, and an impaired airway immune system. These conditions significantly provide an opportunistic platform for NTHi colonization and infection resulting in a “vicious circle.” Episodes of large inflammation as the consequences of multiple interactions between airway immune cells and NTHi, accumulatively contribute to COPD exacerbations and may result in worsening of the clinical status. In this review, we discuss in detail the interplay and crosstalk between airway immune residents and NTHi, and their effect in AECOPD for better understanding of NTHi pathogenesis in COPD patients.",2018 Nov 5,"['Su, Yu-Ching', 'Jalalvand, Farshid', 'Thegerström, John', 'Riesbeck, Kristian']",Front Immunol,,,True
bef31fcf85c2a93a2eeae36e5574372c3aa1c8f1,PMC,"Characterization of rhinovirus C from a 4-year-old boy with acute onset dilated cardiomyopathy in Jakarta, Indonesia",http://dx.doi.org/10.1099/jmmcr.0.005139,PMC6230756,30425833,CC BY,"INTRODUCTION: Myocarditis, inflammation of the heart muscle, can be caused by infections, autoimmune disease or exposure to toxins. The major cause of myocarditis in the paediatric population is viral infection, including coxsackievirus B3, adenovirus, herpesvirus, parvovirus, influenza A and B, and hepatitis. Here, we report the detection of rhinovirus C in a boy with a clinical presentation of myocarditis, suggesting a possible causative role of this virus in this case. CASE PRESENTATION: A previously well 4.5-year-old boy presented with increasing breathlessness for a week prior to admission. He also had upper respiratory tract infection a few days before the event. An echocardiogram revealed severe left ventricle (LV) systolic dysfunction with dilation of the LV. RNA was extracted from serum and two nasal swabs, and tested with conventional PCR at the family level for viruses including enterovirus, dengue, chikungunya, influenza, herpesvirus, paramyxovirus and coronavirus. Further characterization of the enterovirus group was carried out using PCR with primers targeting the VP4/VP2 gene, followed by sequencing. Molecular tests showed the presence of rhinovirus C genetic material in both serum and swab samples. Phylogenetic analysis of the VP4/VP2 region showed 96–97 % similarity with the closest strain isolated in Ulaanbaatar (Mongolia) and Japan in 2012. CONCLUSION: We report the possible association of rhinovirus C and myocarditis in a child presenting with acute onset of dilated cardiomyopathy.",2018 Feb 1,"['Wiyatno, Ageng', 'Febrianti, E. S. Zul', 'Dewantari, Aghnianditya Kresno', 'Myint, Khin Saw', 'Safari, Dodi', 'Idris, Nikmah Salamia']",JMM Case Rep,,,True
f62e14e75bd446217bb09ec6824559f88116c366,PMC,Exchange of amino acids in the H1-haemagglutinin to H3 residues is required for efficient influenza A virus replication and pathology in Tmprss2 knock-out mice,http://dx.doi.org/10.1099/jgv.0.001128,PMC6230768,30084768,CC BY,"The haemagglutinin (HA) of H1N1 and H3N2 influenza A virus (IAV) subtypes has to be activated by host proteases. Previous studies showed that H1N1 virus cannot replicate efficiently in Tmprss2(−/−) knock-out mice whereas H3N2 viruses are able to replicate to the same levels in Tmprss2(−/−) as in wild type (WT) mice. Here, we investigated the sequence requirements for the HA molecule that allow IAV to replicate efficiently in the absence of TMPRSS2. We showed that replacement of the H3 for the H1-loop sequence (amino acids 320 to 329, at the C-terminus of HA(1)) was not sufficient for equal levels of virus replication or severe pathology in Tmprss2(−/−) knock-out mice compared to WT mice. However, exchange of a distant amino acid from H1 to H3 sequence (E31D) in addition to the HA-loop substitution resulted in virus replication in Tmprss2(−/−) knock-out mice that was comparable to WT mice. The higher virus replication and lung damage was associated with increased epithelial damage and higher mortality. Our results provide further evidence and insights into host proteases as a promising target for therapeutic intervention of IAV infections.",2018 Sep 6,"['Lambertz, Ruth L. O.', 'Pippel, Jan', 'Gerhauser, Ingo', 'Kollmus, Heike', 'Anhlan, Darisuren', 'Hrincius, Eike R.', 'Krausze, Joern', 'Kühn, Nora', 'Schughart, Klaus']",J Gen Virol,,,True
7bc3fb2c76ed3a6c75bbdb9c25659902b78f8bd0,PMC,Exchange of amino acids in the H1-haemagglutinin to H3 residues is required for efficient influenza A virus replication and pathology in Tmprss2 knock-out mice,http://dx.doi.org/10.1099/jgv.0.001128,PMC6230768,30084768,CC BY,"The haemagglutinin (HA) of H1N1 and H3N2 influenza A virus (IAV) subtypes has to be activated by host proteases. Previous studies showed that H1N1 virus cannot replicate efficiently in Tmprss2(−/−) knock-out mice whereas H3N2 viruses are able to replicate to the same levels in Tmprss2(−/−) as in wild type (WT) mice. Here, we investigated the sequence requirements for the HA molecule that allow IAV to replicate efficiently in the absence of TMPRSS2. We showed that replacement of the H3 for the H1-loop sequence (amino acids 320 to 329, at the C-terminus of HA(1)) was not sufficient for equal levels of virus replication or severe pathology in Tmprss2(−/−) knock-out mice compared to WT mice. However, exchange of a distant amino acid from H1 to H3 sequence (E31D) in addition to the HA-loop substitution resulted in virus replication in Tmprss2(−/−) knock-out mice that was comparable to WT mice. The higher virus replication and lung damage was associated with increased epithelial damage and higher mortality. Our results provide further evidence and insights into host proteases as a promising target for therapeutic intervention of IAV infections.",2018 Sep 6,"['Lambertz, Ruth L. O.', 'Pippel, Jan', 'Gerhauser, Ingo', 'Kollmus, Heike', 'Anhlan, Darisuren', 'Hrincius, Eike R.', 'Krausze, Joern', 'Kühn, Nora', 'Schughart, Klaus']",J Gen Virol,,,False
af5dfacb6eac020ef858b5223fa8cdc3893f709d,PMC,Pathogens in space: Advancing understanding of pathogen dynamics and disease ecology through landscape genetics,http://dx.doi.org/10.1111/eva.12678,PMC6231466,30459828,CC BY,"Landscape genetics has provided many insights into how heterogeneous landscape features drive processes influencing spatial genetic variation in free‐living organisms. This rapidly developing field has focused heavily on vertebrates, and expansion of this scope to the study of infectious diseases holds great potential for landscape geneticists and disease ecologists alike. The potential application of landscape genetics to infectious agents has garnered attention at formative stages in the development of landscape genetics, but systematic examination is lacking. We comprehensively review how landscape genetics is being used to better understand pathogen dynamics. We characterize the field and evaluate the types of questions addressed, approaches used and systems studied. We also review the now established landscape genetic methods and their realized and potential applications to disease ecology. Lastly, we identify emerging frontiers in the landscape genetic study of infectious agents, including recent phylogeographic approaches and frameworks for studying complex multihost and host‐vector systems. Our review emphasizes the expanding utility of landscape genetic methods available for elucidating key pathogen dynamics (particularly transmission and spread) and also how landscape genetic studies of pathogens can provide insight into host population dynamics. Through this review, we convey how increasing awareness of the complementarity of landscape genetics and disease ecology among practitioners of each field promises to drive important cross‐disciplinary advances.",2018 Jul 28,"['Kozakiewicz, Christopher P.', 'Burridge, Christopher P.', 'Funk, W. Chris', 'VandeWoude, Sue', 'Craft, Meggan E.', 'Crooks, Kevin R.', 'Ernest, Holly B.', 'Fountain‐Jones, Nicholas M.', 'Carver, Scott']",Evol Appl,,,True
f435af9f4c369a6738a5c079f5f9b486cf9e63e2,PMC,Recombinant Infectious Bronchitis Viruses Expressing Chimeric Spike Glycoproteins Induce Partial Protective Immunity against Homologous Challenge despite Limited Replication In Vivo,http://dx.doi.org/10.1128/JVI.01473-18,PMC6232476,30209177,CC BY,"Vaccination regimes against Infectious bronchitis virus (IBV), which are based on a single virus serotype, often induce insufficient levels of cross-protection against serotypes and two or more antigenically diverse vaccines are used in attempt to provide broader protection. Amino acid differences in the surface protein, spike (S), in particular the S1 subunit, are associated with poor cross-protection. Here, homologous vaccination trials with recombinant IBVs (rIBVs), based on the apathogenic strain, BeauR, were conducted to elucidate the role of S1 in protection. A single vaccination of specific-pathogen-free chickens with rIBV expressing S1 of virulent strains M41 or QX, BeauR-M41(S1) and BeauR-QX(S1), gave incomplete protection against homologous challenge, based on ciliary activity and clinical signs. There could be conformational issues with the spike if heterologous S1 and S2 are linked, suggesting a homologous S2 might be essential. To address this, a homologous vaccination-challenge trial incorporating rIBVs expressing full spike from M41, BeauR-M41(S), and S2 subunit from M41, BeauR-M41(S2) was conducted. All chimeric viruses grew to similar titers in vitro, induced virus-specific partial protective immunity, evident by cellular infiltrations, reductions in viral RNA load in the trachea and conjunctiva and higher serum anti-IBV titers. Collectively, these findings show that vaccination with rIBVs primed the birds for challenge but the viruses were cleared rapidly from the mucosal tissues in the head. Chimeric S1 and S2 viruses did not protect as effectively as BeauR-M41(S) based on ciliary activity and clinical signs. Booster vaccinations and an rIBV with improved in vivo replication may improve the levels of protection. IMPORTANCE Infectious bronchitis virus causes an acute, highly contagious respiratory disease, responsible for significant economic losses to the poultry industry. Amino acid differences in the surface protein, spike (S), in particular the S1 subunit, have been associated with poor cross-protection. Available vaccines give poor cross-protection and rationally designed live attenuated vaccines, based on apathogenic BeauR, could address these. Here, to determine the role of S1 in protection, a series of homologous vaccination trials with rIBVs were conducted. Single vaccinations with chimeric rIBVs induced virus-specific partial protective immunity, characterized by reduction in viral load and serum antibody titers. However, BeauR-M41(S) was the only vaccination to improve the level of protection against clinical signs and the loss of tracheal ciliary activity. Growth characteristics show that all of the rIBVs replicated in vitro to similar levels. Booster vaccinations and an rIBV with improved in vivo replication may improve the levels of protection.",2018 Nov 12,"['Ellis, Samantha', 'Keep, Sarah', 'Britton, Paul', 'de Wit, Sjaak', 'Bickerton, Erica', 'Vervelde, Lonneke']",J Virol,,,True
d39a4fdb4c67a86c47496bef56c34f732817b4bf,PMC,NSs Protein of Sandfly Fever Sicilian Phlebovirus Counteracts Interferon (IFN) Induction by Masking the DNA-Binding Domain of IFN Regulatory Factor 3,http://dx.doi.org/10.1128/JVI.01202-18,PMC6232482,30232186,CC BY,"Sandfly fever Sicilian virus (SFSV) is one of the most widespread and frequently identified members of the genus Phlebovirus (order Bunyavirales, family Phenuiviridae) infecting humans. Being transmitted by Phlebotomus sandflies, SFSV causes a self-limiting, acute, often incapacitating febrile disease (“sandfly fever,” “Pappataci fever,” or “dog disease”) that has been known since at least the beginning of the 20th century. We show that, similarly to other pathogenic phleboviruses, SFSV suppresses the induction of the antiviral type I interferon (IFN) system in an NSs-dependent manner. SFSV NSs interfered with the TBK1-interferon regulatory factor 3 (IRF3) branch of the RIG-I signaling pathway but not with NF-κB activation. Consistently, we identified IRF3 as a host interactor of SFSV NSs. In contrast to IRF3, neither the IFN master regulator IRF7 nor any of the related transcription factors IRF2, IRF5, and IRF9 were bound by SFSV NSs. In spite of this specificity for IRF3, NSs did not inhibit its phosphorylation, dimerization, or nuclear accumulation, and the interaction was independent of the IRF3 activation or multimerization state. In further studies, we identified the DNA-binding domain of IRF3 (amino acids 1 to 113) as sufficient for NSs binding and found that SFSV NSs prevented the association of activated IRF3 with the IFN-β promoter. Thus, unlike highly virulent phleboviruses, which either destroy antiviral host factors or sequester whole signaling chains into inactive aggregates, SFSV modulates type I IFN induction by directly masking the DNA-binding domain of IRF3. IMPORTANCE Phleboviruses are receiving increased attention due to the constant discovery of new species and the ongoing spread of long-known members of the genus. Outbreaks of sandfly fever were reported in the 19th century, during World War I, and during World War II. Currently, SFSV is recognized as one of the most widespread phleboviruses, exhibiting high seroprevalence rates in humans and domestic animals and causing a self-limiting but incapacitating disease predominantly in immunologically naive troops and travelers. We show how the nonstructural NSs protein of SFSV counteracts the upregulation of the antiviral interferon (IFN) system. SFSV NSs specifically inhibits promoter binding by IFN transcription factor 3 (IRF3), a molecular strategy which is unique among phleboviruses and, to our knowledge, among human pathogenic RNA viruses in general. This IRF3-specific and stoichiometric mechanism, greatly distinct from the ones exhibited by the highly virulent phleboviruses, correlates with the intermediate level of pathogenicity of SFSV.",2018 Nov 12,"['Wuerth, Jennifer Deborah', 'Habjan, Matthias', 'Wulle, Julia', 'Superti-Furga, Giulio', 'Pichlmair, Andreas', 'Weber, Friedemann']",J Virol,,,True
7d650d31956785474d9b36835d13006b28c508ea,PMC,Association of the Human Bocavirus With Tonsil Squamous Cell Carcinomas,http://dx.doi.org/10.3389/fmicb.2018.02450,PMC6232770,30459721,CC BY,"Background: The human bocavirus (HBoV) is known to persist latently in the infected host cells and seems to replicate its DNA via the DNA damage response system, which is frequently defect in tumors and correlates with microsatellite instability (MSI). Because HBoV is able to persist in the infected tissues, induces pro-fibrotic and pro- cancerogenic cytokines in vivo and in vitro, and is detected in colorectal and lung tumors, the virus may be involved in cancerogenesis at least as a cofactor. Recently it was shown that the adenotonsillar tissue is an important site of HBoV1 persistence and replication. Considering the background that approximately 60% of oropharyngeal cancers were thought to be attributable to a HPV infection, a co-participation of HBoV in terms of a chronic virus infection might play a role in the cancerogenesis of tonsil tumors. Methods: Formalin-fixed, paraffin-embedded tonsil tumor samples were screened for HBoV and HPV DNA. Positive tissue sections were afterward subjected to fluorescence in situ hybridization (FISH) analysis to identify HBoV and HPV infected cells. By use of an in vitro cell culture model with primary tonsil fibroblasts, keratinocytes, and lymphocytes infected by HBoV we tried to find the target cells of virus replication. MSI testing was based on a previously published protocol using a de-multiplexed PCR followed by fluorescent detection of PCR products in a capillary sequencing device. Results: In total 62 of 103 (60, 19%) of the tonsil squamous cell carcinomas tested positive for HBoV DNA and 66 of 103 (66%) samples were identified as HPV positive. The FISH analysis revealed both double infection of HPV and HBoV in the same cells as well as single infections of both viruses within the tumor tissue. Twenty-two of 62 HBoV positive tumors tested HPV negative, 40 of 62 tissue sections were HBoV and HPV positive. We analyzed 21 out of the 62 HBoV positive tumors for MSI. Of those four tonsils displayed MSI in at least 1 of 10 microsatellite markers. Conclusion: Our findings support the hypothesis that human bocavirus infections as a cofactor may have an impact on tumor development in tonsils, although it still remains possible that HBoV solely displays a tumor tropism.",2018 Oct 16,"['Höpken, Merle', 'Förster, Isabel', 'Maune, Steffen', 'Brockmann, Michael', 'Schildgen, Oliver', 'Schildgen, Verena']",Front Microbiol,,,True
0a124d3aa26def70b2db71f68c89dfe1996daf3e,PMC,Euclidean Distance Analysis Enables Nucleotide Skew Analysis in Viral Genomes,http://dx.doi.org/10.1155/2018/6490647,PMC6232797,30510593,CC BY,"Nucleotide skew analysis is a versatile method to study the nucleotide composition of RNA/DNA molecules, in particular to reveal characteristic sequence signatures. For instance, skew analysis of the nucleotide bias of several viral RNA genomes indicated that it is enriched in the unpaired, single-stranded genome regions, thus creating an even more striking virus-specific signature. The comparison of skew graphs for many virus isolates or families is difficult, time-consuming, and nonquantitative. Here, we present a procedure for a more simple identification of similarities and dissimilarities between nucleotide skew data of coronavirus, flavivirus, picornavirus, and HIV-1 RNA genomes. Window and step sizes were normalized to correct for differences in length of the viral genome. Cumulative skew data are converted into pairwise Euclidean distance matrices, which can be presented as neighbor-joining trees. We present skew value trees for the four virus families and show that closely related viruses are placed in small clusters. Importantly, the skew value trees are similar to the trees constructed by a “classical” model of evolutionary nucleotide substitution. Thus, we conclude that the simple calculation of Euclidean distances between nucleotide skew data allows an easy and quantitative comparison of characteristic sequence signatures of virus genomes. These results indicate that the Euclidean distance analysis of nucleotide skew data forms a nice addition to the virology toolbox.",2018 Oct 30,"['van Hemert, Formijn', 'Jebbink, Maarten', 'van der Ark, Andries', 'Scholer, Frits', 'Berkhout, Ben']",Comput Math Methods Med,,,True
88fb5713a61697d45f7d08a3b36012f955d354c9,PMC,Dam characteristics associated with pre-weaning diarrhea in mink (Neovison vison),http://dx.doi.org/10.1186/s13028-018-0427-z,PMC6233364,30419935,CC BY,"BACKGROUND: Pre-weaning diarrhea (PWD) in mink, also known as “sticky kits”, is a frequently occurring syndrome in suckling mink kits on commercial mink farms. Outbreaks of PWD result in weakened kits, increased mortality and reduced growth and welfare as well as considerable economic losses for the farmers. The syndrome is regarded as multifactorial with a complex etiology, and studies have focused on associations with environment, management and dam characteristics. The present study was conducted from May to June 2015 and included 70 dams with mink litters with and without PWD. The aims were to examine associations between PWD and mastitis (bacterial infection and histological signs of inflammation or other lesions in the mammary gland), and to examine associations between PWD and other dam-related characteristics (age, litter size, body mass index, and weight and number of active mammary glands of the dam). RESULTS: Using multivariable mixed logistic regression analyses with farm id as a random intercept, we found that the odds for PWD in the litter were significantly higher in 1 year old dams versus > 1 year old (OR = 13.3, CI 2.0–90.2, P = 0.01), higher if litter size observed after birth was > 5 kits versus ≤ 5 kits (OR = 16.5, CI 2.2–123.7, P = 0.01), higher if the number of active mammary glands per kit was ≤ 1.5 versus > 1.5 glands per kit (OR = 6.5, CI 1.2–36.0), P = 0.03), and higher in farms with high prevalence of PWD versus low prevalence (OR = 16.8, CI 2.9–97.6, P = 0.002). There were no significant associations between PWD and bacterial infection, histological signs of inflammation or other lesions of the mammary gland, body mass index or weight of mammary gland per kit. CONCLUSION: Pre-weaning diarrhea had a statistically significant association with age of the dam, litter size and the number of active mammary glands per kit. However, PWD was not associated with mastitis, body mass index and weight of mammary gland tissue per kit.",2018 Nov 12,"['Birch, Julie Melsted', 'Agger, Jens Frederik', 'Aalbæk, Bent', 'Struve, Tina', 'Hammer, Anne Sofie', 'Jensen, Henrik Elvang']",Acta Vet Scand,,,True
9697849eeaed7f72a196d9ca4d4d8cfad6a8031e,PMC,Broad neutralizing activity of a human monoclonal antibody against H7N9 strains from 2013 to 2017,http://dx.doi.org/10.1038/s41426-018-0182-2,PMC6234208,30425238,CC BY,"H7N9 influenza virus has been circulating among humans for five epidemic waves since it was first isolated in 2013 in China. The recent increase in H7N9 infections during the fifth outbreak in China has caused concerns of a possible pandemic. In this study, we describe a previously characterized human monoclonal antibody, HNIgGA6, obtained by isolating rearranged heavy-chain and light-chain genes from patients who had recovered from H7N9 infections. HNIgGA6 recognized multiple HAs and neutralized the infectivity of 11 out of the 12 H7N9 strains tested, as well as three emerging HPAI H7N9 isolates. The only resistant strain was A/Shanghai/1/2013 (H7N9-SH1), which carries the avian receptor alleles 186V and 226Q in the sialic acid-binding pocket. The mAb broadly neutralized divergent H7N9 strains from 2013 to 2017 and represents a potential alternative treatment for H7N9 interventions.",2018 Nov 14,"['Chen, Cong', 'Liu, Zuliang', 'Liu, Liguo', 'Xiao, Yan', 'Wang, Jianmin', 'Jin, Qi']",Emerg Microbes Infect,,,True
b72fc0df422070e077cfd05d8db51dfb059b9fd7,PMC,Elucidating the Interaction of CF Airway Epithelial Cells and Rhinovirus: Using the Host-Pathogen Relationship to Identify Future Therapeutic Strategies,http://dx.doi.org/10.3389/fphar.2018.01270,PMC6234657,30464745,CC BY,"Chronic lung disease remains the primary cause of mortality in cystic fibrosis (CF). Growing evidence suggests respiratory viral infections are often more severe in CF compared to healthy peers and contributes to pulmonary exacerbations (PEx) and deterioration of lung function. Rhinovirus is the most prevalent respiratory virus detected, particularly during exacerbations in children with CF <5 years old. However, even though rhinoviral infections are likely to be one of the factors initiating the onset of CF lung disease, there is no effective targeted treatment. A better understanding of the innate immune responses by CF airway epithelial cells, the primary site of infection for viruses, is needed to identify why viral infections are more severe in CF. The aim of this review is to present the clinical impact of virus infection in both young children and adults with CF, focusing on rhinovirus infection. Previous in vitro and in vivo investigations looking at the mechanisms behind virus infection will also be summarized. The review will finish on the potential of transcriptomics to elucidate the host-pathogen responses by CF airway cells to viral infection and identify novel therapeutic targets.",2018 Nov 7,"['Ling, Kak-Ming', 'Garratt, Luke W.', 'Lassmann, Timo', 'Stick, Stephen M.', 'Kicic, Anthony', None, None, None]",Front Pharmacol,,,True
e9904ae72aa384d02a168cbee9347f4af5afda06,PMC,Influenza and respiratory syncytial virus screening for the detection of asymptomatically infected patients in hematology and oncology,http://dx.doi.org/10.3205/dgkh000314,PMC6234716,30460173,CC BY,"Introduction: Respiratory syncytial virus (RSV) and influenza virus infections are a significant healthcare risk for immunocompromised patients. In addition to community onset, nosocomial acquisition and transmission may also occur. Detection of asymptomatic shedders (e.g., patients in the incubation period or immunosuppressed long term shedders) facilitates control of nosocomial transmission. Methods: To strengthen the existing infection control concept, a PCR-based screening for RSV and influenza virus was implemented for all patients lacking respiratory symptoms (asymptomatic patients) who were hospitalized on an adult and a pediatric hemato-oncological ward. Laboratory results of this screening were analyzed retrospectively. Results: 665 respiratory specimens were obtained for screening from 251 patients (26% were 18 years and younger) from December 2016 to April 2017. In 23 patients without respiratory symptoms, either influenza virus or RSV infection was found, resulting in a detection rate of about 9%. In 6 patients, the infection was presumably detected during the incubation period, because an increase of viral load was observed in subsequent specimens. Positive screening results facilitated timely implementation of adequate infection control precautions. Nosocomial clusters of RSV or influenza were not detected during the screening period on the two wards. Conclusion: The seasonal screening program expanded our existing infection control concept in terms of patients lacking respiratory symptoms who shed influenza virus or RSV. It enabled us to identify 23 RSV or influenza infections in patients lacking respiratory symptoms in a 4-month period and thus to rapidly take isolation precautions.",2018 Sep 24,"['Baier, Claas', 'Linderkamp, Christin', 'Beilken, Andreas', 'Thol, Felicitas', 'Heuser, Michael', 'Ebadi, Ella', 'Ganzenmueller, Tina', 'Heim, Albert', 'Bange, Franz-Christoph']",GMS Hyg Infect Control,,,True
73aea1df4694235764281acbc9a19b37525b773e,PMC,Exploring challenges of health system preparedness for communicable diseases in Arbaeen mass gathering: a qualitative study,http://dx.doi.org/10.12688/f1000research.15290.1,PMC6234742,30473777,CC BY,"Background: Infectious diseases are common problems in mass gatherings, especially when there is a lack of health system preparedness. Since Iran is one of the most important countries on the walking path of Arbaeen and has a vital role in providing health services to pilgrims, the experiences of health challenges by participants is of key importance. The aim of this study is to explore stakeholders’ experiences on the health system's preparedness and challenges, and to provide suggestions for preventing infectious diseases during the Arbaeen mass gathering. Methods: A qualitative research method was used with a conventional content analysis approach. The number of participants was 17, including 13 executive managers and 4 health policymakers who entered the study among participants. Semi-structured interviews were used to generate the data. Interviews were analyzed by means of content analysis after face-to-face interviews. Results: Data analysis resulted in the extraction of four main themes and 11 sub-themes. Health infrastructure defects in Iraq has three sub-themes (health abandonment in Iraq, the weaknesses in health culture and problems related to the health system); poor control of the causative factors of infectious diseases has three sub-themes (the underlying factors of the prevalence of contagious diseases, health system response to communicable diseases and ignoring the risks of the Arbaeen ceremony); the low perception of risk in pilgrims has three sub-themes (lack of awareness in pilgrims, fatalism in pilgrims and unhygienic belief in pilgrims); and the ineffectiveness of health education has two sub-themes (training shortage in the targeted group and educational content problems) that shows participant’s experiences of the health system's challenges for coping with infectious diseases during the Arbaeen ceremony. Conclusion: Pilgrim-based training, planning and controlling other challenges may change these threats to opportunities and improve the health of participants of the mass gathering of Arbaeen in the region.",2018 Sep 11,"['Karampourian, Arezou', 'Ghomian, Zohreh', 'Khorasani-Zavareh, Davoud']",F1000Res,,,True
1d05dbf38f98918269d71020f0c9ff616548c2df,PMC,"Human rhinovirus spatial-temporal epidemiology in rural coastal Kenya, 2015-2016, observed through outpatient surveillance",http://dx.doi.org/10.12688/wellcomeopenres.14836.2,PMC6234744,30483602,CC BY,"Background: Human rhinovirus (HRV) is the predominant cause of upper respiratory tract infections, resulting in a significant public health burden. The virus circulates as many different types (168), each generating strong homologous, but weak heterotypic, immunity. The influence of these features on transmission patterns of HRV in the community is understudied. Methods: Nasopharyngeal swabs were collected from patients with symptoms of acute respiratory infection (ARI) at nine out-patient facilities across a Health and Demographic Surveillance System between December 2015 and November 2016. HRV was diagnosed by real-time RT-PCR, and the VP4/VP2 genomic region of the positive samples sequenced. Phylogenetic analysis was used to determine the HRV types. Classification models and G-test statistic were used to investigate HRV type spatial distribution. Demographic characteristics and clinical features of ARI were also compared. Results: Of 5,744 NPS samples collected, HRV was detected in 1057 (18.4%), of which 817 (77.3%) were successfully sequenced. HRV species A, B and C were identified in 360 (44.1%), 67 (8.2%) and 390 (47.7%) samples, respectively. In total, 87 types were determined: 39, 10 and 38 occurred within species A, B and C, respectively. HRV types presented heterogeneous temporal patterns of persistence. Spatially, identical types occurred over a wide distance at similar times, but there was statistically significant evidence for clustering of types between health facilities in close proximity or linked by major road networks. Conclusion: This study records a high prevalence of HRV in out-patient presentations exhibiting high type diversity. Patterns of occurrence suggest frequent and independent community invasion of different types. Temporal differences of persistence between types may reflect variation in type-specific population immunity. Spatial patterns suggest either rapid spread or multiple invasions of the same type, but evidence of similar types amongst close health facilities, or along road systems, indicate type partitioning structured by local spread.",2019 Mar 27,"['Morobe, John Mwita', 'Nyiro, Joyce U.', 'Brand, Samuel', 'Kamau, Everlyn', 'Gicheru, Elijah', 'Eyase, Fredrick', 'Otieno, Grieven P.', 'Munywoki, Patrick K.', 'Agoti, C.N.', 'Nokes, D.J.']",Wellcome Open Res,,,True
e63edd41c1aca8fe732d5285a64fcbd45357cdfb,PMC,"Phylogeography, Transmission, and Viral Proteins of Nipah Virus",http://dx.doi.org/10.1007/s12250-018-0050-1,PMC6235768,30311101,CC BY,"Nipah virus (NiV), a zoonotic paramyxovirus belonging to the genus Henipavirus, is classified as a Biosafety Level-4 pathogen based on its high pathogenicity in humans and the lack of available vaccines or therapeutics. Since its initial emergence in 1998 in Malaysia, this virus has become a great threat to domestic animals and humans. Sporadic outbreaks and person-to-person transmission over the past two decades have resulted in hundreds of human fatalities. Epidemiological surveys have shown that NiV is distributed in Asia, Africa, and the South Pacific Ocean, and is transmitted by its natural reservoir, Pteropid bats. Numerous efforts have been made to analyze viral protein function and structure to develop feasible strategies for drug design. Increasing surveillance and preventative measures for the viral infectious disease are urgently needed.",2018 Oct 11,"['Sun, Bangyao', 'Jia, Lijia', 'Liang, Bilin', 'Chen, Quanjiao', 'Liu, Di']",Virol Sin,,,True
79f00b710ef36e1f905f7d4ac5328a3ea56c0fc0,PMC,IFNL4-ΔG is associated with prostate cancer among men at increased risk of sexually transmitted infections,http://dx.doi.org/10.1038/s42003-018-0193-5,PMC6235841,30456312,CC BY,"Sexually transmitted infections can reach the prostate gland where their harmful effects are mediated by innate immunity, including interferons. Humans are polymorphic for the germline dinucleotide variant, rs368234815-TT/ΔG, in the IFNL4 gene encoding interferon λ4. Since the IFNL4-ΔG allele has been linked to impaired viral clearance, we hypothesized that potential exposure to sexually transmitted pathogens, as assessed by the number of lifetime sexual partners, may increase prostate cancer risk in an IFNL4-ΔG-dependent manner. Accordingly, we find that men with 10 or more sexual partners and at least one copy of IFNL4-ΔG have a significantly increased risk of prostate cancer while those with the same number of partners but lacking IFNL4-ΔG do not. Moreover, a test for effect modification shows a positive interaction between the number of lifetime partners and IFNL4-ΔG in the development of aggressive prostate cancer. Based on these findings, we conclude that a gene–environment interaction between IFNL4-ΔG and sexual activity may increase the risk of prostate cancer.",2018 Nov 14,"['Minas, Tsion Zewdu', 'Tang, Wei', 'Smith, Cheryl J.', 'Onabajo, Olusegun O.', 'Obajemu, Adeola', 'Dorsey, Tiffany H.', 'Jordan, Symone V.', 'Obadi, Obadi M.', 'Ryan, Bríd M.', 'Prokunina-Olsson, Ludmila', 'Loffredo, Christopher A.', 'Ambs, Stefan']",Commun Biol,,,True
99acb5c35e12a8faa8d0f4bc507642a63713414f,PMC,IFNL4-ΔG is associated with prostate cancer among men at increased risk of sexually transmitted infections,http://dx.doi.org/10.1038/s42003-018-0193-5,PMC6235841,30456312,CC BY,"Sexually transmitted infections can reach the prostate gland where their harmful effects are mediated by innate immunity, including interferons. Humans are polymorphic for the germline dinucleotide variant, rs368234815-TT/ΔG, in the IFNL4 gene encoding interferon λ4. Since the IFNL4-ΔG allele has been linked to impaired viral clearance, we hypothesized that potential exposure to sexually transmitted pathogens, as assessed by the number of lifetime sexual partners, may increase prostate cancer risk in an IFNL4-ΔG-dependent manner. Accordingly, we find that men with 10 or more sexual partners and at least one copy of IFNL4-ΔG have a significantly increased risk of prostate cancer while those with the same number of partners but lacking IFNL4-ΔG do not. Moreover, a test for effect modification shows a positive interaction between the number of lifetime partners and IFNL4-ΔG in the development of aggressive prostate cancer. Based on these findings, we conclude that a gene–environment interaction between IFNL4-ΔG and sexual activity may increase the risk of prostate cancer.",2018 Nov 14,"['Minas, Tsion Zewdu', 'Tang, Wei', 'Smith, Cheryl J.', 'Onabajo, Olusegun O.', 'Obajemu, Adeola', 'Dorsey, Tiffany H.', 'Jordan, Symone V.', 'Obadi, Obadi M.', 'Ryan, Bríd M.', 'Prokunina-Olsson, Ludmila', 'Loffredo, Christopher A.', 'Ambs, Stefan']",Commun Biol,,,True
dc5164d2e228cba949bf1e085edef598e23ce967,PMC,Transcriptomic insights into the early host-pathogen interaction of cat intestine with Toxoplasma gondii,http://dx.doi.org/10.1186/s13071-018-3179-8,PMC6236892,30428922,CC BY,"BACKGROUND: Although sexual reproduction of the parasite Toxoplasma gondii exclusively occurs in the cat intestine, knowledge about the alteration of gene expression in the intestine of cats infected with T. gondii is still limited. Here, we investigated the temporal transcriptional changes that occur in the cat intestine during T. gondii infection. METHODS: Cats were infected with 100 T. gondii cysts and their intestines were collected at 6, 12, 18, 24, 72 and 96 hours post-infection (hpi). RNA sequencing (RNA-Seq) Illumina technology was used to gain insight into the spectrum of genes that are differentially expressed due to infection. Quantitative RT-PCR (qRT-PCR) was also used to validate the level of expression of a set of differentially expressed genes (DEGs) obtained by sequencing. RESULTS: Our transcriptome analysis revealed 2363 DEGs that were clustered into six unique patterns of gene expression across all the time points after infection. Our analysis revealed 56, 184, 404, 508, 400 and 811 DEGs in infected intestines compared to uninfected controls at 6, 12, 18, 24, 72 and 96 hpi, respectively. RNA-Seq results were confirmed by qRT-PCR. DEGs were mainly enriched in catalytic activity and metabolic process based on gene ontology enrichment analysis. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that transcriptional changes in the intestine of infected cats evolve over the course of infection, and the largest difference in the enriched pathways was observed at 96 hpi. The anti-T. gondii defense response of the feline host was mediated by Major Histocompatibility Complex class I, proteasomes, heat-shock proteins and fatty acid binding proteins. CONCLUSIONS: This study revealed novel host factors, which may be critical for the successful establishment of an intracellular niche during T. gondii infection in the definitive feline host. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-018-3179-8) contains supplementary material, which is available to authorized users.",2018 Nov 14,"['Wang, Meng', 'Zhang, Fu-Kai', 'Elsheikha, Hany M.', 'Zhang, Nian-Zhang', 'He, Jun-Jun', 'Luo, Jian-Xun', 'Zhu, Xing-Quan']",Parasit Vectors,,,True
9dcd697b97cd39fbeaf2c5f8be7d0bc139b84629,PMC,Critically ill healthcare workers with the middle east respiratory syndrome (MERS): A multicenter study,http://dx.doi.org/10.1371/journal.pone.0206831,PMC6237307,30439974,CC BY,"BACKGROUND: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) leads to healthcare-associated transmission to patients and healthcare workers with potentially fatal outcomes. AIM: We aimed to describe the clinical course and functional outcomes of critically ill healthcare workers (HCWs) with MERS. METHODS: Data on HCWs was extracted from a multi-center retrospective cohort study on 330 critically ill patients with MERS admitted between (9/2012–9/2015). Baseline demographics, interventions and outcomes were recorded and compared between survivors and non-survivors. Survivors were approached with questionnaires to elucidate their functional outcomes using Karnofsky Performance Status Scale. FINDINGS: Thirty-Two HCWs met the inclusion criteria. Comorbidities were recorded in 34% (11/32) HCW. Death resulted in 8/32 (25%) HCWs including all 5 HCWs with chronic renal impairment at baseline. Non-surviving HCW had lower PaO2/FiO2 ratios 63.5 (57, 116.2) vs 148 (84, 194.3), p = 0.043, and received more ECMO therapy compared to survivors, 9/32 (28%) vs 4/24 (16.7%) respectively (p = 0.02).Thirteen of the surviving (13/24) HCWs responded to the questionnaire. Two HCWs confirmed functional limitations. Median number of days from hospital discharge until the questionnaires were filled was 580 (95% CI 568, 723.5) days. CONCLUSION: Approximately 10% of critically ill patients with MERS were HCWs. Hospital mortality rate was substantial (25%). Patients with chronic renal impairment represented a particularly high-risk group that should receive extra caution during suspected or confirmed MERS cases clinical care assignment and during outbreaks. Long-term repercussions of critical illness due to MERS on HCWs in particular, and patients in general, remain unknown and should be investigated in larger studies.",2018 Nov 15,"['Shalhoub, Sarah', 'Al-Hameed, Fahad', 'Mandourah, Yasser', 'Balkhy, Hanan H.', 'Al-Omari, Awad', 'Al Mekhlafi, Ghaleb. A.', 'Kharaba, Ayman', 'Alraddadi, Basem', 'Almotairi, Abdullah', 'Al Khatib, Kasim', 'Abdulmomen, Ahmed', 'Qushmaq, Ismael', 'Mady, Ahmed', 'Solaiman, Othman', 'Al-Aithan, Abdulsalam M.', 'Al-Raddadi, Rajaa', 'Ragab, Ahmed', 'Al Harthy, Abdulrahman', 'Al Qasim, Eman', 'Jose, Jesna', 'Al-Ghamdi, Ghassan', 'Merson, Laura', 'Fowler, Robert', 'Hayden, Frederick G.', 'Arabi, Yaseen M.']",PLoS One,,,True
96602c07c439a97e001abcd2e9c85fda998d64c6,PMC,A unique intra-molecular fidelity-modulating mechanism identified in a viral RNA-dependent RNA polymerase,http://dx.doi.org/10.1093/nar/gky848,PMC6237809,30239956,CC BY,"Typically not assisted by proofreading, the RNA-dependent RNA polymerases (RdRPs) encoded by the RNA viruses may need to independently control its fidelity to fulfill virus viability and fitness. However, the precise mechanism by which the RdRP maintains its optimal fidelity level remains largely elusive. By solving 2.1–2.5 Å resolution crystal structures of the classical swine fever virus (CSFV) NS5B, an RdRP with a unique naturally fused N-terminal domain (NTD), we identified high-resolution intra-molecular interactions between the NTD and the RdRP palm domain. In order to dissect possible regulatory functions of NTD, we designed mutations at residues Y471 and E472 to perturb key interactions at the NTD–RdRP interface. When crystallized, some of these NS5B interface mutants maintained the interface, while the others adopted an ‘open’ conformation that no longer retained the intra-molecular interactions. Data from multiple in vitro RdRP assays indicated that the perturbation of the NTD–RdRP interactions clearly reduced the fidelity level of the RNA synthesis, while the processivity of the NS5B elongation complex was not affected. Collectively, our work demonstrates an explicit and unique mode of polymerase fidelity modulation and provides a vivid example of co-evolution in multi-domain enzymes.",2018 Nov 16,"['Liu, Weichi', 'Shi, Xiaoling', 'Gong, Peng']",Nucleic Acids Res,,,True
1d11f9f1f58c71f5c521649a1bfd43ddedb5c94e,PMC,A unique intra-molecular fidelity-modulating mechanism identified in a viral RNA-dependent RNA polymerase,http://dx.doi.org/10.1093/nar/gky848,PMC6237809,30239956,CC BY,"Typically not assisted by proofreading, the RNA-dependent RNA polymerases (RdRPs) encoded by the RNA viruses may need to independently control its fidelity to fulfill virus viability and fitness. However, the precise mechanism by which the RdRP maintains its optimal fidelity level remains largely elusive. By solving 2.1–2.5 Å resolution crystal structures of the classical swine fever virus (CSFV) NS5B, an RdRP with a unique naturally fused N-terminal domain (NTD), we identified high-resolution intra-molecular interactions between the NTD and the RdRP palm domain. In order to dissect possible regulatory functions of NTD, we designed mutations at residues Y471 and E472 to perturb key interactions at the NTD–RdRP interface. When crystallized, some of these NS5B interface mutants maintained the interface, while the others adopted an ‘open’ conformation that no longer retained the intra-molecular interactions. Data from multiple in vitro RdRP assays indicated that the perturbation of the NTD–RdRP interactions clearly reduced the fidelity level of the RNA synthesis, while the processivity of the NS5B elongation complex was not affected. Collectively, our work demonstrates an explicit and unique mode of polymerase fidelity modulation and provides a vivid example of co-evolution in multi-domain enzymes.",2018 Nov 16,"['Liu, Weichi', 'Shi, Xiaoling', 'Gong, Peng']",Nucleic Acids Res,,,False
bf473015ec0534efc1d29bbdc3a9c37034eeb749,PMC,"Vaccines, inspiring innovation in health()",http://dx.doi.org/10.1016/j.vaccine.2018.05.035,PMC6238075,29789241,CC BY,"This report covers the topics of pandemics, epidemics and partnerships, including regulatory convergence initiatives, new technologies and novel vaccines, discussed by leading public and private sector stakeholders at the 18th Annual General Meeting (AGM) of the Developing Countries Vaccine Manufacturers’ Network (DCVMN). Contributions of Gavi and the vaccine industry from emerging countries to the growing global vaccine market, by improving the supply base from manufacturers in developing countries and contributing to 58% of doses, were highlighted. The Coalition for Epidemic Preparedness Innovations (CEPI), the International Vaccine Institute (IVI) and others reported on new strategies to ensure speedy progress in preclinical and clinical development of innovative vaccines for future MERS, Zika or other outbreak response. Priorities for vaccine stockpiling, to assure readiness during emergencies and to prevent outbreaks due to re-emerging diseases such as yellow fever, cholera and poliomyelitis, were outlined. The role of partnerships in improving global vaccine access, procurement and immunization coverage, and shared concerns were reviewed. The World Health Organization (WHO) and other international collaborating partners provided updates on the Product, Price and Procurement database, the prequalification of vaccines, the control of neglected tropical diseases, particularly the new rabies elimination initiative, and regulatory convergence proposals to accelerate vaccine registration in developing countries. Updates on supply chain innovations and novel vaccine platforms were presented. The discussions enabled members and partners to reflect on efficiency of research & development, supply chain tools and trends in packaging technologies improving delivery of existing vaccines, and allowing a deeper understanding of the current public-health objectives, industry financing, and global policies, required to ensure optimal investments, alignment and stability of vaccine supply in developing countries.",2018 Nov 19,"['Pagliusi, Sonia', 'Dennehy, Maureen', 'Kim, Hun', None]",Vaccine,,,False
2890249daa0601affd680a8aadee19b50ed2044d,PMC,Kinome-Wide siRNA Screening Identifies Src-Enhanced Resistance of Chemotherapeutic Drugs in Triple-Negative Breast Cancer Cells,http://dx.doi.org/10.3389/fphar.2018.01285,PMC6238227,30473665,CC BY,"Background: Chemotherapy is the main treatment for triple-negative breast cancer (TNBC), which lack molecular markers for diagnosis and therapy. Cancer cells activate chemoresistant pathways and lead to therapeutic failure for patients with TNBC. Several kinases have been identified as chemoresistant genes. However, the involvement of kinases in the chemoresistance in TNBC cells is not fully understood. Methods: We employed a kinome siRNA library to screen whether targeting any kinases could increase the chemosensitivity of TNBC cell lines. The effects of kinase on cell viability in various breast cancer cells were validated with ATP level and colony formation. Protein expression and phosphorylation were determined by immunoblotting. The Cancer Genome Atlas (TCGA) dataset was collected to analyze the correlation of Src expression with prognosis of TNBC patients. Results: Primary screening and validation for the initial hits showed that Src kinase was a potential doxorubicin-resistant kinase in the TNBC cell lines MDA-MB-231 and Hs578T. Both siRNA against Src and the Src inhibitor dasatinib enhanced the cytotoxic effects of doxorubicin in TNBC cells. Moreover, phosphorylation of AKT and signal transducer and activator of transcription 3 (STAT3), downstream effectors of Src, were accordingly decreased in Src-silenced or -inhibited TNBC cells. Additionally, TCGA data analysis indicated that Src expression levels in tumor tissues were higher than those in tumor-adjacent normal tissues in patients with TNBC. High co-expression level of Src and STAT3 was also significantly correlated with poor prognosis in patients. Conclusion: Our results showed that Src-STAT3 axis might be involved in chemoresistance of TNBC cells.",2018 Nov 9,"['Tzeng, Yen-Dun Tony', 'Liu, Pei-Feng', 'Li, Ju-Yueh', 'Liu, Li-Feng', 'Kuo, Soong-Yu', 'Hsieh, Chiao-Wei', 'Lee, Cheng-Hsin', 'Wu, Chih-Hsuan', 'Hsiao, Michael', 'Chang, Hong-Tai', 'Shu, Chih-Wen']",Front Pharmacol,,,True
ea023fc02c5314abb3e56a827e5eac71de12db9b,PMC,In situ Immune Signatures and Microbial Load at the Nasopharyngeal Interface in Children With Acute Respiratory Infection,http://dx.doi.org/10.3389/fmicb.2018.02475,PMC6238668,30473680,CC BY,"Acute respiratory infection (ARI) is the most frequent cause for hospitalization in infants and young children. Using multiplexed nCounter technology to digitally quantify 600 human mRNAs in parallel with 14 virus- and 5 bacterium-specific RNAs, we characterized viral and bacterial presence in nasopharyngeal aspirates (NPA) of 58 children with ARI and determined the corresponding in situ immune profiles. NPA contained different groups of organisms and these were classified into bacterial (n = 27), viral (n = 5), codetection [containing both viral and bacterial transcripts (n = 21), or indeterminate intermediate where microbial load is below threshold (n = 5)]. We then identified differentially expressed immune transcripts (DEITs) comparing NPAs from symptomatic children vs. healthy controls, and comparing children presenting NPAs with detectable microbial load vs. indeterminate. We observed a strong innate immune response in NPAs, due to the presence of evolutionarily conserved type I Interferon (IFN)-stimulated genes (ISG), which was correlated with total bacterial and/or viral load. In comparison with indeterminate NPAs, adaptive immunity transcripts discriminated among viral, bacterial, and codetected microbial profiles. In viral NPAs, B cell transcripts were significantly enriched among DEITs, while only type III IFN was correlated with viral load. In bacterial NPAs, myeloid cells and coinhibitory transcripts were enriched and significantly correlated with bacterial load. In conclusion, digital nCounter transcriptomics provide a microbial and immunological in situ “snapshot” of the nasopharyngeal interface in children with ARI. This enabled discrimination among viral, bacterial, codetection, and indeterminate transcripts in the samples using non-invasive sampling.",2018 Nov 9,"['Fukutani, Kiyoshi F.', 'Nascimento-Carvalho, Cristiana M.', 'Bouzas, Maiara L.', 'Oliveira, Juliana R.', 'Barral, Aldina', 'Dierckx, Tim', 'Khouri, Ricardo', 'Nakaya, Helder I.', 'Andrade, Bruno B.', 'Van Weyenbergh, Johan', 'de Oliveira, Camila I.']",Front Microbiol,,,True
c5e5ce1e093a5acef8221d3f5cd3926cd8f9a87f,PMC,"Emerging vector-borne diseases in dromedaries in Tunisia: West Nile, bluetongue, epizootic haemorrhagic disease and Rift Valley fever",http://dx.doi.org/10.4102/ojvr.v84i1.1316,PMC6238681,28397519,CC BY,"A total of 118 sera were collected during 2016 from two groups of dromedaries from Kebili and Medenine governorates in the south of Tunisia. The aim of this study was to provide the first serological investigation of four emerging vector-borne diseases in two groups of dromedaries in Tunisia. Sera were tested by ELISA and serum neutralisation test to identify West Nile virus (WNV), bluetongue virus (BTV), epizootic haemorrhagic disease virus (EHDV) and Rift Valley fever virus (RVFV). In the first group, the seroprevalence for BTV was 4.6%, while in the second group, it was 25.8% for WNV and 9.7% for BTV. Only serotype 1 was detected for BTV in the two groups. No evidence for circulation of RVF and EHD viruses was revealed. Results indicated that dromedaries can be infected with BTV and WNV, suggesting that this species might play a significant role in the epizootiology of these viral diseases in Tunisia and neighbouring countries.",2017 Mar 31,"['Hassine, Thameur B.', 'Amdouni, Jihane', 'Monaco, Federica', 'Savini, Giovanni', 'Sghaier, Soufien', 'Selimen, Imed B.', 'Chandoul, Walid', 'Hamida, Khaled B.', 'Hammami, Salah']",Onderstepoort J Vet Res,,,True
114b18b271ebb99486d88b94f526864870ec4f11,PMC,Health evaluation of African penguins (Spheniscus demersus) in southern Africa,http://dx.doi.org/10.4102/ojvr.v83i1.1147,PMC6238701,27796116,CC BY,"The African penguin (Spheniscus demersus) is an endangered seabird that breeds along the coast of Namibia and South Africa, and disease surveillance was identified as a priority for its conservation. Aiming for the establishment of baseline data on the presence of potential pathogens in this species, a comprehensive health assessment (blood smear examination, haematology, biochemistry and serology) was conducted on samples obtained from 578 African penguins at 11 breeding colonies and a rehabilitation centre. There were 68 penguins that were seropositive for at least one of seven pathogens tested: avian encephalomyelitis virus, avian infectious bronchitis virus, avian reovirus, infectious bursal disease virus, Newcastle disease virus, Mycoplasma gallisepticum and Mycoplasma synoviae. All samples were seronegative for avian influenza virus subtypes H5 and H7 and infectious laryngotracheitis virus. The apparent prevalence of Babesia sp. and Borrelia sp. in blood smears was consistent with previous studies. Babesia-infected individuals had a regenerative response of the erythrocytic lineage, an active inflammatory response and hepatic function impairment. These findings indicate that African penguins may be exposed to conservation-significant pathogens in the wild and encourage further studies aiming for the direct detection and/or isolation of these microorganisms.",2016 Sep 20,"['Parsons, Nola J.', 'Gous, Tertius A.', 'Schaefer, Adam M.', 'Vanstreels, Ralph E.T.']",Onderstepoort J Vet Res,,,True
cc146665ee73fa1830b7c42a24cd5844346c0f39,PMC,"Detection of central nervous system viral infections in adults in Manado, North Sulawesi, Indonesia",http://dx.doi.org/10.1371/journal.pone.0207440,PMC6239303,30444898,CC0,"Central nervous system (CNS) viral infections are important causes of morbidity and mortality worldwide but the systematic survey of patients admitted to hospitals with CNS infections in many countries, including Indonesia, is limited. To obtain more information regarding the causes of CNS infections in Indonesia, this study was performed to detect and identify viral agents associated with CNS infections amongst in-patients at a referral hospital in Manado, North Sulawesi, Indonesia. Adult patients admitted to R.D. Kandou General Hospital with presumed CNS infection were enrolled. Cerebrospinal fluid, serum, and throat swab samples were collected and tested using molecular, serological, and virus isolation assays. A confirmed viral etiology was established in three and a probable/possible in 11 out of 74 patients. The most common was herpes simplex virus 1 (7/74, 9.5%), followed by Epstein-Barr virus (2/74, 2.7%), cytomegalovirus (1/74, 1.4%), enterovirus D68 (1/74, 1.4%), rhinovirus A (1/74, 1.4%), dengue virus (1/64, 1.6%), and Japanese encephalitis virus (1/64, 1.6%). There were 20 fatal cases (27.0%) during hospitalization in which eight were associated with viral causes. We identified herpes simplex virus 1 as the most common cause of CNS infection among adults in North Sulawesi with most of the cases remaining undiagnosed. Our study highlights the challenges in establishing the etiology of viral CNS infections and the importance of using a wide range of molecular and serological detection methods to identify CNS viruses.",2018 Nov 16,"['Mawuntu, Arthur H. P.', 'Bernadus, Janno B. B.', 'Dhenni, Rama', 'Wiyatno, Ageng', 'Anggreani, Riane', 'Feliana,', 'Yudhaputri, Frilasita A.', 'Jaya, Ungke Anton', 'Ma’roef, Chairin Nisa', 'Dewantari, Aghnianditya K.', 'Fadhilah, Araniy', 'Ledermann, Jeremy P.', 'Powers, Ann M.', 'Safari, Dodi', 'Myint, Khin Saw Aye']",PLoS One,,,True
a1c5f9bbda77a176030cb8975c30ab34faed8dcc,PMC,"Detection of central nervous system viral infections in adults in Manado, North Sulawesi, Indonesia",http://dx.doi.org/10.1371/journal.pone.0207440,PMC6239303,30444898,CC0,"Central nervous system (CNS) viral infections are important causes of morbidity and mortality worldwide but the systematic survey of patients admitted to hospitals with CNS infections in many countries, including Indonesia, is limited. To obtain more information regarding the causes of CNS infections in Indonesia, this study was performed to detect and identify viral agents associated with CNS infections amongst in-patients at a referral hospital in Manado, North Sulawesi, Indonesia. Adult patients admitted to R.D. Kandou General Hospital with presumed CNS infection were enrolled. Cerebrospinal fluid, serum, and throat swab samples were collected and tested using molecular, serological, and virus isolation assays. A confirmed viral etiology was established in three and a probable/possible in 11 out of 74 patients. The most common was herpes simplex virus 1 (7/74, 9.5%), followed by Epstein-Barr virus (2/74, 2.7%), cytomegalovirus (1/74, 1.4%), enterovirus D68 (1/74, 1.4%), rhinovirus A (1/74, 1.4%), dengue virus (1/64, 1.6%), and Japanese encephalitis virus (1/64, 1.6%). There were 20 fatal cases (27.0%) during hospitalization in which eight were associated with viral causes. We identified herpes simplex virus 1 as the most common cause of CNS infection among adults in North Sulawesi with most of the cases remaining undiagnosed. Our study highlights the challenges in establishing the etiology of viral CNS infections and the importance of using a wide range of molecular and serological detection methods to identify CNS viruses.",2018 Nov 16,"['Mawuntu, Arthur H. P.', 'Bernadus, Janno B. B.', 'Dhenni, Rama', 'Wiyatno, Ageng', 'Anggreani, Riane', 'Feliana,', 'Yudhaputri, Frilasita A.', 'Jaya, Ungke Anton', 'Ma’roef, Chairin Nisa', 'Dewantari, Aghnianditya K.', 'Fadhilah, Araniy', 'Ledermann, Jeremy P.', 'Powers, Ann M.', 'Safari, Dodi', 'Myint, Khin Saw Aye']",PLoS One,,,False
c7bf679ec25305b15089e89885f393de974be10d,PMC,Development of luciferase-linked antibody capture assay based on luciferase immunoprecipitation systems for antibody detection of porcine reproductive and respiratory syndrome virus,http://dx.doi.org/10.1186/s12896-018-0483-5,PMC6240198,30445953,CC BY,"BACKGROUND: Early detection of porcine reproductive and respiratory syndrome virus (PRRSV) infection of swine is necessary to control this devastating disease. By monitoring host serum antibodies to viral antigens, early virus detection within herds is feasible. In this study, recombinant antigens were generated using recombinant DNA techniques to fuse PRRSV structural protein (N) or nonstructural protein 1α (nsp1α) with the Rellina luciferase gene. Next, fused genes were cloned into plasmids and transfected into HEK-293 T cells for transient expression. Upon co-incubation of lysates with pig sera, antigen-antibody complexes formed that bound to Protein-G coated onto microplates. By further measurement of luminance value, a modified form of Luciferase Immunoprecipitation Systems, namely luciferase-linked antibody capture assay (LACA) was developed for detection of PRRSV-specific antibodies. RESULTS: Known anti-PRRSV antibody-positive or -negative serum samples (125 and 122 samples, respectively) were used to validate the LACA and compared it with IDEXX PRRS ×3 ELISA. Based on the result, N-Rluc and nsp1α-Rluc LACA results were 95.3 and 94.4% in agreement with IDEXX ELISA, suggested a similar specificity of LACA to IDEXX ELISA. Moreover, when both LACA and IDEXX ELISA were used to evaluate sequential serum samples obtained from PRRSV experimentally infected pigs, the PRRSV-specific antibody response was detectable as early as 3 days post-inoculation (dpi) using N-Rluc LACA, but undetectable until 7 dpi using IDEXX ELISA, suggesting an improved sensitivity of LACA. Meanwhile, antibodies specific for nsp1α were detected at higher levels overall, but were undetectable until 10 dpi. Furthermore,. Notably, one IDEXX ELISA positive result was not confirmed by LACA or IFA and was thus considered a false-positive result. CONCLUSION: The LACA exhibited similar specificity but improved sensitivity to that of the commercial IDEXX PRRS ×3 ELISA kit for detection of PRRSV-specific antibodies in pig serum. Importantly, LACA could be adapted for detecting antibodies against other PRRSV targets, such as nsp1α, to achieve earlier detection of PRRSV infection.",2018 Nov 16,"['Li, Jie', 'Wang, Gang', 'Yang, Di', 'Zhao, Bao', 'Zhao, Yongpan', 'Liu, Yonggang', 'Cai, Xuehui', 'Nan, Yuchen', 'Zhou, En-Min', 'Wu, Chunyan']",BMC Biotechnol,,,True
db7b306a406cd633344a193033ac15a798b1d1d8,PMC,Chile’s role in global health diplomacy: a narrative literature review,http://dx.doi.org/10.1186/s12992-018-0428-8,PMC6240220,30445983,CC BY,"BACKGROUND: Global health diplomacy (GHD) has become an important field of investigation due to health concerns increasingly entering the foreign policy domain. Much of the existing academic writing focuses on North-South cooperation in global health, and emphasizes the role of security and economic interests by Northern countries as drivers of GHD. Chile presents a favourable environment for an expanded involvement in future GHD activities. However, there is little knowledge about what has been driving Chile’s integration of health into foreign policy, and little effort to appropriate knowledge from international relations theories to better theoretically grasp the emergence of GHD. METHODS: To fill this knowledge gap, we conducted a narrative literature review of the driving forces behind Chile’s integration of health into foreign policy. Drawing on a popular analytical framework used in international relations scholarship, we identified driving forces of the integration of health into Chile foreign policy at three levels of analysis. RESULTS: At the international/global level of analysis, the main driving forces were related to national security concerns and compliance with regulations of international organizations. At the regional level, GHD was driven by a commitment to regional solidarity through mutually beneficial cooperation in response to neoliberal reforms; health coordination in emergencies; and protection of indigenous peoples. Finally, at the domestic level, drivers identified include economic interests of various productive sectors and how health regulations might impact those; the high degree of social inequity which impacts on access to healthcare; and management of natural disasters. CONCLUSION: Health actions in the context of international relations in Chile are still mainly motivated by more traditional foreign policy interests rather than by a desire to satisfy health needs per se. This seems to conform with findings of existing GHD scholarship that emphasize the importance of security and economic interests as driving forces of GHD, and how health is often appropriated instrumentally within foreign policy settings to achieve other goals. But the review also reveals that in the context of South-South cooperation (and regional health diplomacy), solidarity and normative considerations can be important driving forces as well. Finally, the review demonstrates that there has been an evolution from chiefly domestically focused health policies (e.g. maternal and child nutrition treatment) towards internationally inspired integrated policies (e.g. maternal and child nutrition promotion aligned with international guidelines). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12992-018-0428-8) contains supplementary material, which is available to authorized users.",2018 Nov 16,"['Ramírez, Jorge', 'Valdivia, Leonel', 'Rivera, Elena', 'da Silva Santos, Marilia', 'Sepúlveda, Dino', 'Labonté, Ronald', 'Ruckert, Arne']",Global Health,,,True
8b4bf48f0df4492821623ee6951fc65503514846,PMC,USP18 – a multifunctional component in the interferon response,http://dx.doi.org/10.1042/BSR20180250,PMC6240716,30126853,CC BY,"Ubiquitin-specific proteases (USPs) represent the largest family of deubiquitinating enzymes (DUB). These proteases cleave the isopeptide bond between ubiquitin and a lysine residue of a ubiquitin-modified protein. USP18 is a special member of the USP family as it only deconjugates the ubiquitin-like protein ISG15 (interferon-stimulated gene (ISG) 15) from target proteins but is not active towards ubiquitin. Independent of its protease activity, USP18 functions as a major negative regulator of the type I interferon response showing that USP18 is – at least – a bifunctional protein. In this review, we summarise our current knowledge of protease-dependent and -independent functions of USP18 and discuss the structural basis of its dual activity.",2018 Nov 16,"['Basters, Anja', 'Knobeloch, Klaus-Peter', 'Fritz, Günter']",Biosci Rep,,,True
8863943c0c9153a3677761f16e704854c65c3783,PMC,EGFR as a Negative Regulatory Protein Adjusts the Activity and Mobility of NHE3 in the Cell Membrane of IPEC-J2 Cells With TGEV Infection,http://dx.doi.org/10.3389/fmicb.2018.02734,PMC6243134,30483239,CC BY,"Transmissible gastroenteritis (TGE) has caused devastating economic losses to the swine industry worldwide, despite extensive research focusing on the pathogenesis of virus infection. The molecular pathogenic mechanism of TGEV-induced diarrhea in piglets is unknown. Intestinal diarrhea is closely related to the function of the Na(+)/H(+) exchanger protein NHE3 in the brush border membrane of small intestine epithelial cells. The epidermal growth factor receptor (EGFR) may act to regulate NHE3 expression. In addition, EGFR may promote viral invasion of host cells. The present study aimed to determine whether NHE3 activity is regulated by altering EGFR expression to affect Na(+) absorption in TGEV-infected intestinal epithelial cells. Porcine intestinal epithelial cells were used as models for TGEV infection. The results showed that Na(+) absorption and NHE3 expression levels decreased in TGEV-infected cells. Proliferation of TGEV within IPEC-J2 cells could be inhibited by treatment with the EGFR inhibitor AG1478 and knockdown; resulting in recovery of Na(+) absorption in TGEV infected cells and increasing the activity and expression of NHE3. Moreover, we demonstrated that NHE3 activity was regulated through the EGFR/ERK pathway. Importantly, NHE3 mobility on the plasma membrane of TGEV infected cells was significantly weaker than that in normal cells, and EGFR inhibition and knockdown recovered this mobility. Our research indicated that NHE3 activity was negatively regulated by EGFR in TGEV-infected intestinal epithelial cells.",2018 Nov 13,"['Yang, Zhou', 'Ran, Ling', 'Yuan, Peng', 'Yang, Yang', 'Wang, Kai', 'Xie, Luyi', 'Huang, Shilei', 'Liu, Jia', 'Song, Zhenhui']",Front Microbiol,,,True
bcb677ce41cddf93a9177fc07934c414c7b8dbe2,PMC,Climate Change Could Increase the Geographic Extent of Hendra Virus Spillover Risk,http://dx.doi.org/10.1007/s10393-018-1322-9,PMC6245089,29556762,CC BY,"Disease risk mapping is important for predicting and mitigating impacts of bat-borne viruses, including Hendra virus (Paramyxoviridae:Henipavirus), that can spillover to domestic animals and thence to humans. We produced two models to estimate areas at potential risk of HeV spillover explained by the climatic suitability for its flying fox reservoir hosts, Pteropus alecto and P. conspicillatus. We included additional climatic variables that might affect spillover risk through other biological processes (such as bat or horse behaviour, plant phenology and bat foraging habitat). Models were fit with a Poisson point process model and a log-Gaussian Cox process. In response to climate change, risk expanded southwards due to an expansion of P. alecto suitable habitat, which increased the number of horses at risk by 175–260% (110,000–165,000). In the northern limits of the current distribution, spillover risk was highly uncertain because of model extrapolation to novel climatic conditions. The extent of areas at risk of spillover from P. conspicillatus was predicted shrink. Due to a likely expansion of P. alecto into these areas, it could replace P. conspicillatus as the main HeV reservoir. We recommend: (1) HeV monitoring in bats, (2) enhancing HeV prevention in horses in areas predicted to be at risk, (3) investigate and develop mitigation strategies for areas that could experience reservoir host replacements. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10393-018-1322-9) contains supplementary material, which is available to authorized users.",2018 Mar 19,"['Martin, Gerardo', 'Yanez-Arenas, Carlos', 'Chen, Carla', 'Plowright, Raina K.', 'Webb, Rebecca J.', 'Skerratt, Lee F.']",Ecohealth,,,False
62df738127972a011de37d5c27776c48442889a9,PMC,Climate Change Could Increase the Geographic Extent of Hendra Virus Spillover Risk,http://dx.doi.org/10.1007/s10393-018-1322-9,PMC6245089,29556762,CC BY,"Disease risk mapping is important for predicting and mitigating impacts of bat-borne viruses, including Hendra virus (Paramyxoviridae:Henipavirus), that can spillover to domestic animals and thence to humans. We produced two models to estimate areas at potential risk of HeV spillover explained by the climatic suitability for its flying fox reservoir hosts, Pteropus alecto and P. conspicillatus. We included additional climatic variables that might affect spillover risk through other biological processes (such as bat or horse behaviour, plant phenology and bat foraging habitat). Models were fit with a Poisson point process model and a log-Gaussian Cox process. In response to climate change, risk expanded southwards due to an expansion of P. alecto suitable habitat, which increased the number of horses at risk by 175–260% (110,000–165,000). In the northern limits of the current distribution, spillover risk was highly uncertain because of model extrapolation to novel climatic conditions. The extent of areas at risk of spillover from P. conspicillatus was predicted shrink. Due to a likely expansion of P. alecto into these areas, it could replace P. conspicillatus as the main HeV reservoir. We recommend: (1) HeV monitoring in bats, (2) enhancing HeV prevention in horses in areas predicted to be at risk, (3) investigate and develop mitigation strategies for areas that could experience reservoir host replacements. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10393-018-1322-9) contains supplementary material, which is available to authorized users.",2018 Mar 19,"['Martin, Gerardo', 'Yanez-Arenas, Carlos', 'Chen, Carla', 'Plowright, Raina K.', 'Webb, Rebecca J.', 'Skerratt, Lee F.']",Ecohealth,,,True
eac85c85c3a2ac1d3fe53e1e3b3fee98f52527ad,PMC,"Evaluation of preparedness of healthcare student volunteers against Middle East respiratory syndrome coronavirus (MERS-CoV) in Makkah, Saudi Arabia: a cross-sectional study",http://dx.doi.org/10.1007/s10389-018-0917-5,PMC6245094,30533343,CC BY,"AIM: To assess the knowledge and attitude of senior medical, dental, nursing and pharmacy students toward Middle East respiratory syndrome-corona virus (MERS-CoV) in Saudi Arabia. SUBJECTS AND METHODS: A cross-sectional survey using a 21-item questionnaire was conducted for a 3-month period from November 2015–January 2016 in Makkah, Saudi Arabia. The questionnaire was designed to evaluate students’ understanding and perception of MERS-CoV. An ANOVA test was used to determine the association of study discipline and academic year with the student knowledge score on MERS. RESULTS: A total of 364 students were assessed during the study. The majority (62%) of the participants were in the 20–22-year age group. More than half (53%) were pharmacy students followed by (22%) medical students. More than two thirds (71%) of the participants were aware that MERS is caused by the coronavirus. More than half (59%) of the participants believed that MERS can be transmitted through direct or indirect contact with infected camels. A statistically significant association was reported between the study discipline and mean knowledge score (p < 0.0001) with medical students achieving an overall better knowledge score compared with students from other study disciplines. CONCLUSION: Overall, students had good knowledge about MERS epidemiology, transmission and the recommended protective measures. However, students expressed their reluctance to work in healthcare facilities with inadequate MERS infection control isolation policies.",2018 Apr 14,"['Elrggal, Mahmoud E.', 'Karami, Nedaa A.', 'Rafea, Bushra', 'Alahmadi, Lama', 'Al Shehri, Anwar', 'Alamoudi, Ruba', 'Koshak, Hassan', 'Alkahtani, Saad', 'Cheema, Ejaz']",Z Gesundh Wiss,,,True
b2d2e361791ad3dc669a11f7a0fb57cacbc01285,PMC,"Assessing the Methods, Tools, and Statistical Approaches in Google Trends Research: Systematic Review",http://dx.doi.org/10.2196/jmir.9366,PMC6246971,30401664,CC BY,"BACKGROUND: In the era of information overload, are big data analytics the answer to access and better manage available knowledge? Over the last decade, the use of Web-based data in public health issues, that is, infodemiology, has been proven useful in assessing various aspects of human behavior. Google Trends is the most popular tool to gather such information, and it has been used in several topics up to this point, with health and medicine being the most focused subject. Web-based behavior is monitored and analyzed in order to examine actual human behavior so as to predict, better assess, and even prevent health-related issues that constantly arise in everyday life. OBJECTIVE: This systematic review aimed at reporting and further presenting and analyzing the methods, tools, and statistical approaches for Google Trends (infodemiology) studies in health-related topics from 2006 to 2016 to provide an overview of the usefulness of said tool and be a point of reference for future research on the subject. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for selecting studies, we searched for the term “Google Trends” in the Scopus and PubMed databases from 2006 to 2016, applying specific criteria for types of publications and topics. A total of 109 published papers were extracted, excluding duplicates and those that did not fall inside the topics of health and medicine or the selected article types. We then further categorized the published papers according to their methodological approach, namely, visualization, seasonality, correlations, forecasting, and modeling. RESULTS: All the examined papers comprised, by definition, time series analysis, and all but two included data visualization. A total of 23.1% (24/104) studies used Google Trends data for examining seasonality, while 39.4% (41/104) and 32.7% (34/104) of the studies used correlations and modeling, respectively. Only 8.7% (9/104) of the studies used Google Trends data for predictions and forecasting in health-related topics; therefore, it is evident that a gap exists in forecasting using Google Trends data. CONCLUSIONS: The monitoring of online queries can provide insight into human behavior, as this field is significantly and continuously growing and will be proven more than valuable in the future for assessing behavioral changes and providing ground for research using data that could not have been accessed otherwise.",2018 Nov 6,"['Mavragani, Amaryllis', 'Ochoa, Gabriela', 'Tsagarakis, Konstantinos P']",J Med Internet Res,,,False
8125e22d2dc5ad5fe51394fc08dc89212c833d2c,PMC,Molecular Basis for the Evolution of Species-Specific Hemoglobin Capture by Staphylococcus aureus,http://dx.doi.org/10.1128/mBio.01524-18,PMC6247092,30459189,CC BY,"Metals are a limiting resource for pathogenic bacteria and must be scavenged from host proteins. Hemoglobin provides the most abundant source of iron in the human body and is required by several pathogens to cause invasive disease. However, the consequences of hemoglobin evolution for bacterial nutrient acquisition remain unclear. Here we show that the α- and β-globin genes exhibit strikingly parallel signatures of adaptive evolution across simian primates. Rapidly evolving sites in hemoglobin correspond to binding interfaces of IsdB, a bacterial hemoglobin receptor harbored by pathogenic Staphylococcus aureus. Using an evolution-guided experimental approach, we demonstrate that the divergence between primates and staphylococcal isolates governs hemoglobin recognition and bacterial growth. The reintroduction of putative adaptive mutations in α- or β-globin proteins was sufficient to impair S. aureus binding, providing a mechanism for the evolution of disease resistance. These findings suggest that bacterial hemoprotein capture has driven repeated evolutionary conflicts with hemoglobin during primate descent.",2018 Nov 20,"['Choby, Jacob E.', 'Buechi, Hanna B.', 'Farrand, Allison J.', 'Skaar, Eric P.', 'Barber, Matthew F.']",mBio,,,True
0537823ee7ac420f3f6e1a1261afa425dd4cd1a6,PMC,Development of a Conventional RT-PCR Assay for Rapid Detection of Porcine Deltacoronavirus with the Same Detection Limit as a SYBR Green-Based Real-Time RT-PCR Assay,http://dx.doi.org/10.1155/2018/5035139,PMC6247729,30533434,CC BY,"Porcine deltacoronavirus (PDCoV) is a newly discovered coronavirus, which belongs to the family Coronaviridae. It causes watery diarrhea, vomiting, and dehydration in newborn piglets. A sensitive RT-PCR method is urgently required to detect PDCoV infection. In this study, we developed and evaluated a conventional RT-PCR assay and a SYBR green-based real-time RT-PCR assay that targeted the PDCoV n gene. Both assays are specific and have the same limit of detection at 2 × 10(1) copies of RNA molecules per reaction. Eighty-four clinical samples were subjected to both conventional RT-PCR and real-time RT-PCR, and the same positive rate (41.7%) was achieved, which was much higher than the positive rate (26.2%) using a previously described one-step RT-PCR technique. In summary, a conventional RT-PCR technique was successfully established for the detection of PDCoV with the same detection limit as a SYBR green-based real-time RT-PCR assay.",2018 Nov 6,"['Ma, Lei', 'Zeng, Fanwen', 'Huang, Bihong', 'Cong, Feng', 'Huang, Ren', 'Ma, Jingyun', 'Guo, Pengju']",Biomed Res Int,,,True
e411c54208dfc5d918d46642a7f1694fcc681cf4,PMC,"Epidemiology of severe acute respiratory infections from hospital-based surveillance in Madagascar, November 2010 to July 2013",http://dx.doi.org/10.1371/journal.pone.0205124,PMC6248916,30462659,CC BY,"BACKGROUND: Few comprehensive data exist regarding the epidemiology of severe acute respiratory infections (SARI) in low income countries. This study aimed at identifying etiologies and describing clinical features of SARI-associated hospitalization in Madagascar. METHODS: It is a prospective surveillance of SARI in 2 hospitals for 3 years. Nasopharyngeal swabs, sputum, and blood were collected from SARI patients enrolled and tested for viruses and bacteria. Epidemiological and clinical information were obtained from case report forms. RESULTS: Overall, 876 patients were enrolled in the study, of which 83.1% (728/876) were tested positive for at least one pathogen. Viral and bacterial infections occurred in 76.1% (667/876) and 35.8% (314/876) of tested samples, respectively. Among all detected viruses, respiratory syncytial virus (RSV) was the most common (37.7%; 348/924) followed by influenza virus A (FLUA, 18.4%; 170/924), rhinovirus (RV, 13.5%; 125/924), and adenovirus (ADV, 8.3%; 77/924). Among bacteria, Streptococcus pneumoniae (S. pneumoniae, 50.3%, 189/370) was the most detected followed by Haemophilus influenzae type b (Hib, 21.4%; 79/370), and Klebsiella (4.6%; 17/370). Other Streptococcus species were found in 8.1% (30/370) of samples. Compared to patients aged less than 5 years, older age groups were significantly less infected with RSV. On the other hand, patients aged more than 64 years (OR = 3.66) were at higher risk to be infected with FLUA, while those aged 15–29 years (OR = 3.22) and 30–64 years (OR = 2.39) were more likely to be infected with FLUB (influenza virus B). CONCLUSION: The frequency of influenza viruses detected among SARI patients aged 65 years and more highlights the need for health authorities to develop strategies to reduce morbidity amongst at-risk population through vaccine recommendation. Amongst young children, the demonstrated burden of RSV should guide clinicians for a better case management of children. These findings reveal the need to develop point-of-care tests to avoid overuse of antibiotics and to promote vaccine that could reduce drastically the RSV hospitalizations.",2018 Nov 21,"['Razanajatovo, Norosoa Harline', 'Guillebaud, Julia', 'Harimanana, Aina', 'Rajatonirina, Soatiana', 'Ratsima, Elisoa Hariniaina', 'Andrianirina, Zo Zafitsara', 'Rakotoariniaina, Hervé', 'Andriatahina, Todisoa', 'Orelle, Arnaud', 'Ratovoson, Rila', 'Irinantenaina, Judickaelle', 'Rakotonanahary, Dina Arinalina', 'Ramparany, Lovasoa', 'Randrianirina, Frédérique', 'Richard, Vincent', 'Heraud, Jean-Michel']",PLoS One,,,True
e2500283a378472050282da03b7d5e9612e4e5ec,PMC,"Seasonal and interannual risks of dengue introduction from South-East Asia into China, 2005-2015",http://dx.doi.org/10.1371/journal.pntd.0006743,PMC6248995,30412575,CC BY,"Due to worldwide increased human mobility, air-transportation data and mathematical models have been widely used to measure risks of global dispersal of pathogens. However, the seasonal and interannual risks of pathogens importation and onward transmission from endemic countries have rarely been quantified and validated. We constructed a modelling framework, integrating air travel, epidemiological, demographical, entomological and meteorological data, to measure the seasonal probability of dengue introduction from endemic countries. This framework has been applied retrospectively to elucidate spatiotemporal patterns and increasing seasonal risk of dengue importation from South-East Asia into China via air travel in multiple populations, Chinese travelers and local residents, over a decade of 2005–15. We found that the volume of airline travelers from South-East Asia into China has quadrupled from 2005 to 2015 with Chinese travelers increased rapidly. Following the growth of air traffic, the probability of dengue importation from South-East Asia into China has increased dramatically from 2005 to 2015. This study also revealed seasonal asymmetries of transmission routes: Sri Lanka and Maldives have emerged as origins; neglected cities at central and coastal China have been increasingly vulnerable to dengue importation and onward transmission. Compared to the monthly occurrence of dengue reported in China, our model performed robustly for importation and onward transmission risk estimates. The approach and evidence could facilitate to understand and mitigate the changing seasonal threat of arbovirus from endemic regions.",2018 Nov 9,"['Lai, Shengjie', 'Johansson, Michael A.', 'Yin, Wenwu', 'Wardrop, Nicola A.', 'van Panhuis, Willem G.', 'Wesolowski, Amy', 'Kraemer, Moritz U. G.', 'Bogoch, Isaac I.', 'Kain, Dylain', 'Findlater, Aidan', 'Choisy, Marc', 'Huang, Zhuojie', 'Mu, Di', 'Li, Yu', 'He, Yangni', 'Chen, Qiulan', 'Yang, Juan', 'Khan, Kamran', 'Tatem, Andrew J.', 'Yu, Hongjie']",PLoS Negl Trop Dis,,,True
1d034e288cb8c4eb1f407a4f61d9c553ea30a670,PMC,"Seasonal and interannual risks of dengue introduction from South-East Asia into China, 2005-2015",http://dx.doi.org/10.1371/journal.pntd.0006743,PMC6248995,30412575,CC BY,"Due to worldwide increased human mobility, air-transportation data and mathematical models have been widely used to measure risks of global dispersal of pathogens. However, the seasonal and interannual risks of pathogens importation and onward transmission from endemic countries have rarely been quantified and validated. We constructed a modelling framework, integrating air travel, epidemiological, demographical, entomological and meteorological data, to measure the seasonal probability of dengue introduction from endemic countries. This framework has been applied retrospectively to elucidate spatiotemporal patterns and increasing seasonal risk of dengue importation from South-East Asia into China via air travel in multiple populations, Chinese travelers and local residents, over a decade of 2005–15. We found that the volume of airline travelers from South-East Asia into China has quadrupled from 2005 to 2015 with Chinese travelers increased rapidly. Following the growth of air traffic, the probability of dengue importation from South-East Asia into China has increased dramatically from 2005 to 2015. This study also revealed seasonal asymmetries of transmission routes: Sri Lanka and Maldives have emerged as origins; neglected cities at central and coastal China have been increasingly vulnerable to dengue importation and onward transmission. Compared to the monthly occurrence of dengue reported in China, our model performed robustly for importation and onward transmission risk estimates. The approach and evidence could facilitate to understand and mitigate the changing seasonal threat of arbovirus from endemic regions.",2018 Nov 9,"['Lai, Shengjie', 'Johansson, Michael A.', 'Yin, Wenwu', 'Wardrop, Nicola A.', 'van Panhuis, Willem G.', 'Wesolowski, Amy', 'Kraemer, Moritz U. G.', 'Bogoch, Isaac I.', 'Kain, Dylain', 'Findlater, Aidan', 'Choisy, Marc', 'Huang, Zhuojie', 'Mu, Di', 'Li, Yu', 'He, Yangni', 'Chen, Qiulan', 'Yang, Juan', 'Khan, Kamran', 'Tatem, Andrew J.', 'Yu, Hongjie']",PLoS Negl Trop Dis,,,True
5b381a6fa91b64fc105ba7fda01dd12f53358cbc,PMC,Pre-B acute lymphoblastic leukemia expresses cell surface nucleolin as a 9-O-acetylated sialoglycoprotein,http://dx.doi.org/10.1038/s41598-018-33873-2,PMC6249323,30464179,CC BY,"Precursor B acute lymphoblastic leukemias (pre-B ALLs) abnormally express a specific glycan structure, 9-O-acetylated sialic acid (9-O-Ac-Sia), on their cell surface, but glycoproteins that carry this modification have not been identified. Using three different lectins that specifically recognize this structure, we establish that nucleolin (NCL), a protein implicated in cancer, contains 9-O-Ac-Sia. Surprisingly, antibodies against the glycolipid 9-O-Ac-Sia GD3 also detected 9-O-Ac-Sia NCL. NCL is present on the surface of pre-B ALL cells as a sialoglycoprotein that is partly 9-O-acetylated and conversely, 9-O-Ac-Sia-containing structures other than NCL are present on these cells as well. Interestingly, NCL and the 9-O-Ac-Sia signal had less co-localization on normal pre-B cells. We also investigated regulation of NCL on the cell surface and found that sialidase treatment increased the percentage of cells positive for cell surface NCL, suggesting that sialylation of NCL promotes internalization. Treatment of pre-B ALL cells with the chemotherapy drug vincristine also increased the percentage of cells with surface NCL and correlated with increased 9-O-Ac-Sia expression. All tested leukemia cells including primary samples expressed NCL, suggesting it as a possible therapeutic target. We confirmed this by showing inhibition of cell proliferation in some pre-B ALLs by exposure to a NCL-specific aptamer AS1411.",2018 Nov 21,"['Joo, Eun Ji', 'Wasik, Brian R', 'Parrish, Colin', 'Paz, Helicia', 'Mϋhlenhoff, Martina', 'Abdel-Azim, Hisham', 'Groffen, John', 'Heisterkamp, Nora']",Sci Rep,,,False
9cab4a22cd4bba56a4f3a8fb9040bb96a8ea48a9,PMC,Pre-B acute lymphoblastic leukemia expresses cell surface nucleolin as a 9-O-acetylated sialoglycoprotein,http://dx.doi.org/10.1038/s41598-018-33873-2,PMC6249323,30464179,CC BY,"Precursor B acute lymphoblastic leukemias (pre-B ALLs) abnormally express a specific glycan structure, 9-O-acetylated sialic acid (9-O-Ac-Sia), on their cell surface, but glycoproteins that carry this modification have not been identified. Using three different lectins that specifically recognize this structure, we establish that nucleolin (NCL), a protein implicated in cancer, contains 9-O-Ac-Sia. Surprisingly, antibodies against the glycolipid 9-O-Ac-Sia GD3 also detected 9-O-Ac-Sia NCL. NCL is present on the surface of pre-B ALL cells as a sialoglycoprotein that is partly 9-O-acetylated and conversely, 9-O-Ac-Sia-containing structures other than NCL are present on these cells as well. Interestingly, NCL and the 9-O-Ac-Sia signal had less co-localization on normal pre-B cells. We also investigated regulation of NCL on the cell surface and found that sialidase treatment increased the percentage of cells positive for cell surface NCL, suggesting that sialylation of NCL promotes internalization. Treatment of pre-B ALL cells with the chemotherapy drug vincristine also increased the percentage of cells with surface NCL and correlated with increased 9-O-Ac-Sia expression. All tested leukemia cells including primary samples expressed NCL, suggesting it as a possible therapeutic target. We confirmed this by showing inhibition of cell proliferation in some pre-B ALLs by exposure to a NCL-specific aptamer AS1411.",2018 Nov 21,"['Joo, Eun Ji', 'Wasik, Brian R', 'Parrish, Colin', 'Paz, Helicia', 'Mϋhlenhoff, Martina', 'Abdel-Azim, Hisham', 'Groffen, John', 'Heisterkamp, Nora']",Sci Rep,,,True
dc66ab3c756846482cc8d1d6abd41b623027fbf1,PMC,Development of Clinical-Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease in Nonhuman Primates,http://dx.doi.org/10.1093/infdis/jiy285,PMC6249601,29860496,CC BY,"BACKGROUND: For most classes of drugs, rapid development of therapeutics to treat emerging infections is challenged by the timelines needed to identify compounds with the desired efficacy, safety, and pharmacokinetic profiles. Fully human monoclonal antibodies (mAbs) provide an attractive method to overcome many of these hurdles to rapidly produce therapeutics for emerging diseases. METHODS: In this study, we deployed a platform to generate, test, and develop fully human antibodies to Zaire ebolavirus. We obtained specific anti-Ebola virus (EBOV) antibodies by immunizing VelocImmune mice that use human immunoglobulin variable regions in their humoral responses. RESULTS: Of the antibody clones isolated, 3 were selected as best at neutralizing EBOV and triggering FcγRIIIa. Binding studies and negative-stain electron microscopy revealed that the 3 selected antibodies bind to non-overlapping epitopes, including a potentially new protective epitope not targeted by other antibody-based treatments. When combined, a single dose of a cocktail of the 3 antibodies protected nonhuman primates (NHPs) from EBOV disease even after disease symptoms were apparent. CONCLUSIONS: This antibody cocktail provides complementary mechanisms of actions, incorporates novel specificities, and demonstrates high-level postexposure protection from lethal EBOV disease in NHPs. It is now undergoing testing in normal healthy volunteers in preparation for potential use in future Ebola epidemics.",2018 Dec 15,"['Pascal, Kristen E', 'Dudgeon, Drew', 'Trefry, John C', 'Anantpadma, Manu', 'Sakurai, Yasuteru', 'Murin, Charles D', 'Turner, Hannah L', 'Fairhurst, Jeanette', 'Torres, Marcela', 'Rafique, Ashique', 'Yan, Ying', 'Badithe, Ashok', 'Yu, Kevin', 'Potocky, Terra', 'Bixler, Sandra L', 'Chance, Taylor B', 'Pratt, William D', 'Rossi, Franco D', 'Shamblin, Joshua D', 'Wollen, Suzanne E', 'Zelko, Justine M', 'Carrion, Ricardo', 'Worwa, Gabriella', 'Staples, Hilary M', 'Burakov, Darya', 'Babb, Robert', 'Chen, Gang', 'Martin, Joel', 'Huang, Tammy T', 'Erlandson, Karl', 'Willis, Melissa S', 'Armstrong, Kimberly', 'Dreier, Thomas M', 'Ward, Andrew B', 'Davey, Robert A', 'Pitt, Margaret L M', 'Lipsich, Leah', 'Mason, Peter', 'Olson, William', 'Stahl, Neil', 'Kyratsous, Christos A']",J Infect Dis,,,True
0401a5bebe76fc07dde0f103a248118ce30facda,PMC,Comparison of enzyme-linked immunosorbent assay systems using rift valley fever virus nucleocapsid protein and inactivated virus as antigens,http://dx.doi.org/10.1186/s12985-018-1071-y,PMC6249750,30466469,CC BY,"BACKGROUND: Rift Valley Fever (RVF) is a mosquito-borne viral zoonosis. To detect RVF virus (RVFV) infection, indirect immunoglobulin G (IgG) and immunoglobulin M (IgM) enzyme linked immunosorbent assays (ELISAs) which utilize recombinant RVFV nucleocapsid (RVFV-N) protein as assay antigen, have reportedly been used, however, there is still a need to develop more sensitive and specific methods of detection. METHODS: RVFV-N protein was expressed in Escherichia coli (E. coli) and purified by histidine-tag based affinity chromatography. This recombinant RVFV-N (rRVFV-N) protein was then used as antigen to develop an IgG sandwich ELISA and IgM capture ELISAs for human sera. Ninety six serum samples collected from healthy volunteers during the RVF surveillance programme in Kenya in 2013, and 93 serum samples collected from RVF-suspected patients during the 2006–2007 RVF outbreak in Kenya were used respectively, to evaluate the newly established rRVFV-N protein-based IgG sandwich ELISA and IgM capture ELISA systems in comparison with the inactivated virus-based ELISA systems. RESULTS: rRVFV-N protein-based-IgG sandwich ELISA and IgM capture ELISA for human sera were established. Both the new ELISA systems were in 100% concordance with the inactivated virus-based ELISA systems, with a sensitivity and specificity of 100%. CONCLUSIONS: Recombinant RVFV-N is a safe and affordable antigen for RVF diagnosis. Our rRVFV-N-based ELISA systems are safe and reliable tools for diagnosis of RVFV infection in humans and especially useful in large-scale epidemiological investigation and for application in developing countries.",2018 Nov 22,"['Yu, Fuxun', 'Adungo, Ferdinard', 'Konongoi, Samson Limbaso', 'Inoue, Shingo', 'Sang, Rosemary', 'Ashur, Salame', 'Kwallah, Allan ole', 'Uchida, Leo', 'Buerano, Corazon C', 'Mwau, Matilu', 'Zha, Yan', 'Nie, Yingjie', 'Morita, Kouichi']",Virol J,,,True
4015a1657c31d90fb5f1a47c4f83f495785fa428,PMC,Influence of viral infection on the relationships between airway cytokines and lung function in asthmatic children,http://dx.doi.org/10.1186/s12931-018-0922-9,PMC6249926,30463560,CC BY,"BACKGROUND: Few longitudinal studies examine inflammation and lung function in asthma. We sought to determine the cytokines that reduce airflow, and the influence of respiratory viral infections on these relationships. METHODS: Children underwent home collections of nasal lavage during scheduled surveillance periods and self-reported respiratory illnesses. We studied 53 children for one year, analyzing 392 surveillance samples and 203 samples from 85 respiratory illnesses. Generalized estimated equations were used to evaluate associations between nasal lavage biomarkers (7 mRNAs, 10 proteins), lung function and viral infection. RESULTS: As anticipated, viral infection was associated with increased cytokines and reduced FVC and FEV(1). However, we found frequent and strong interactions between biomarkers and virus on lung function. For example, in the absence of viral infection, CXCL10 mRNA, MDA5 mRNA, CXCL10, IL-4, IL-13, CCL4, CCL5, CCL20 and CCL24 were negatively associated with FVC. In contrast, during infection, the opposite relationship was frequently found, with IL-4, IL-13, CCL5, CCL20 and CCL24 levels associated with less severe reductions in both FVC and FEV(1). CONCLUSIONS: In asthmatic children, airflow obstruction is driven by specific pro-inflammatory cytokines. In the absence of viral infection, higher cytokine levels are associated with decreasing lung function. However, with infection, there is a reversal in this relationship, with cytokine abundance associated with reduced lung function decline. While nasal samples may not reflect lower airway responses, these data suggest that some aspects of the inflammatory response may be protective against viral infection. This study may have ramifications for the treatment of viral-induced asthma exacerbations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-018-0922-9) contains supplementary material, which is available to authorized users.",2018 Nov 21,"['Lewis, Toby C.', 'Metitiri, Ediri E.', 'Mentz, Graciela B.', 'Ren, Xiaodan', 'Carpenter, Ashley R.', 'Goldsmith, Adam M.', 'Wicklund, Kyra E.', 'Eder, Breanna N.', 'Comstock, Adam T.', 'Ricci, Jeannette M.', 'Brennan, Sean R.', 'Washington, Ginger L.', 'Owens, Kendall B.', 'Mukherjee, Bhramar', 'Robins, Thomas G.', 'Batterman, Stuart A.', 'Hershenson, Marc B.', None]",Respir Res,,,False
de5857aebe3d89d5a3c404de6a9a365cc68e3051,PMC,Influence of viral infection on the relationships between airway cytokines and lung function in asthmatic children,http://dx.doi.org/10.1186/s12931-018-0922-9,PMC6249926,30463560,CC BY,"BACKGROUND: Few longitudinal studies examine inflammation and lung function in asthma. We sought to determine the cytokines that reduce airflow, and the influence of respiratory viral infections on these relationships. METHODS: Children underwent home collections of nasal lavage during scheduled surveillance periods and self-reported respiratory illnesses. We studied 53 children for one year, analyzing 392 surveillance samples and 203 samples from 85 respiratory illnesses. Generalized estimated equations were used to evaluate associations between nasal lavage biomarkers (7 mRNAs, 10 proteins), lung function and viral infection. RESULTS: As anticipated, viral infection was associated with increased cytokines and reduced FVC and FEV(1). However, we found frequent and strong interactions between biomarkers and virus on lung function. For example, in the absence of viral infection, CXCL10 mRNA, MDA5 mRNA, CXCL10, IL-4, IL-13, CCL4, CCL5, CCL20 and CCL24 were negatively associated with FVC. In contrast, during infection, the opposite relationship was frequently found, with IL-4, IL-13, CCL5, CCL20 and CCL24 levels associated with less severe reductions in both FVC and FEV(1). CONCLUSIONS: In asthmatic children, airflow obstruction is driven by specific pro-inflammatory cytokines. In the absence of viral infection, higher cytokine levels are associated with decreasing lung function. However, with infection, there is a reversal in this relationship, with cytokine abundance associated with reduced lung function decline. While nasal samples may not reflect lower airway responses, these data suggest that some aspects of the inflammatory response may be protective against viral infection. This study may have ramifications for the treatment of viral-induced asthma exacerbations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-018-0922-9) contains supplementary material, which is available to authorized users.",2018 Nov 21,"['Lewis, Toby C.', 'Metitiri, Ediri E.', 'Mentz, Graciela B.', 'Ren, Xiaodan', 'Carpenter, Ashley R.', 'Goldsmith, Adam M.', 'Wicklund, Kyra E.', 'Eder, Breanna N.', 'Comstock, Adam T.', 'Ricci, Jeannette M.', 'Brennan, Sean R.', 'Washington, Ginger L.', 'Owens, Kendall B.', 'Mukherjee, Bhramar', 'Robins, Thomas G.', 'Batterman, Stuart A.', 'Hershenson, Marc B.', None]",Respir Res,,,False
e7eab33081228b6405ecc7a3d97fb803aca119ae,PMC,Influence of viral infection on the relationships between airway cytokines and lung function in asthmatic children,http://dx.doi.org/10.1186/s12931-018-0922-9,PMC6249926,30463560,CC BY,"BACKGROUND: Few longitudinal studies examine inflammation and lung function in asthma. We sought to determine the cytokines that reduce airflow, and the influence of respiratory viral infections on these relationships. METHODS: Children underwent home collections of nasal lavage during scheduled surveillance periods and self-reported respiratory illnesses. We studied 53 children for one year, analyzing 392 surveillance samples and 203 samples from 85 respiratory illnesses. Generalized estimated equations were used to evaluate associations between nasal lavage biomarkers (7 mRNAs, 10 proteins), lung function and viral infection. RESULTS: As anticipated, viral infection was associated with increased cytokines and reduced FVC and FEV(1). However, we found frequent and strong interactions between biomarkers and virus on lung function. For example, in the absence of viral infection, CXCL10 mRNA, MDA5 mRNA, CXCL10, IL-4, IL-13, CCL4, CCL5, CCL20 and CCL24 were negatively associated with FVC. In contrast, during infection, the opposite relationship was frequently found, with IL-4, IL-13, CCL5, CCL20 and CCL24 levels associated with less severe reductions in both FVC and FEV(1). CONCLUSIONS: In asthmatic children, airflow obstruction is driven by specific pro-inflammatory cytokines. In the absence of viral infection, higher cytokine levels are associated with decreasing lung function. However, with infection, there is a reversal in this relationship, with cytokine abundance associated with reduced lung function decline. While nasal samples may not reflect lower airway responses, these data suggest that some aspects of the inflammatory response may be protective against viral infection. This study may have ramifications for the treatment of viral-induced asthma exacerbations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-018-0922-9) contains supplementary material, which is available to authorized users.",2018 Nov 21,"['Lewis, Toby C.', 'Metitiri, Ediri E.', 'Mentz, Graciela B.', 'Ren, Xiaodan', 'Carpenter, Ashley R.', 'Goldsmith, Adam M.', 'Wicklund, Kyra E.', 'Eder, Breanna N.', 'Comstock, Adam T.', 'Ricci, Jeannette M.', 'Brennan, Sean R.', 'Washington, Ginger L.', 'Owens, Kendall B.', 'Mukherjee, Bhramar', 'Robins, Thomas G.', 'Batterman, Stuart A.', 'Hershenson, Marc B.', None]",Respir Res,,,True
8c97d3d01a4d77e5f4f458ed46ba5399f3647a74,PMC,Respiratory Viral Infection-Induced Microbiome Alterations and Secondary Bacterial Pneumonia,http://dx.doi.org/10.3389/fimmu.2018.02640,PMC6250824,30505304,CC BY,"Influenza and other respiratory viral infections are the most common type of acute respiratory infection. Viral infections predispose patients to secondary bacterial infections, which often have a more severe clinical course. The mechanisms underlying post-viral bacterial infections are complex, and include multifactorial processes mediated by interactions between viruses, bacteria, and the host immune system. Studies over the past 15 years have demonstrated that unique microbial communities reside on the mucosal surfaces of the gastrointestinal tract and the respiratory tract, which have both direct and indirect effects on host defense against viral infections. In addition, antiviral immune responses induced by acute respiratory infections such as influenza are associated with changes in microbial composition and function (“dysbiosis”) in the respiratory and gastrointestinal tract, which in turn may alter subsequent immune function against secondary bacterial infection or alter the dynamics of inter-microbial interactions, thereby enhancing the proliferation of potentially pathogenic bacterial species. In this review, we summarize the literature on the interactions between host microbial communities and host defense, and how influenza, and other acute respiratory viral infections disrupt these interactions, thereby contributing to the pathogenesis of secondary bacterial infections.",2018 Nov 16,"['Hanada, Shigeo', 'Pirzadeh, Mina', 'Carver, Kyle Y.', 'Deng, Jane C.']",Front Immunol,,,True
6a01f63d60f9a6c658db8b35ef0189c1d10b6112,PMC,Respiratory Viral Infection-Induced Microbiome Alterations and Secondary Bacterial Pneumonia,http://dx.doi.org/10.3389/fimmu.2018.02640,PMC6250824,30505304,CC BY,"Influenza and other respiratory viral infections are the most common type of acute respiratory infection. Viral infections predispose patients to secondary bacterial infections, which often have a more severe clinical course. The mechanisms underlying post-viral bacterial infections are complex, and include multifactorial processes mediated by interactions between viruses, bacteria, and the host immune system. Studies over the past 15 years have demonstrated that unique microbial communities reside on the mucosal surfaces of the gastrointestinal tract and the respiratory tract, which have both direct and indirect effects on host defense against viral infections. In addition, antiviral immune responses induced by acute respiratory infections such as influenza are associated with changes in microbial composition and function (“dysbiosis”) in the respiratory and gastrointestinal tract, which in turn may alter subsequent immune function against secondary bacterial infection or alter the dynamics of inter-microbial interactions, thereby enhancing the proliferation of potentially pathogenic bacterial species. In this review, we summarize the literature on the interactions between host microbial communities and host defense, and how influenza, and other acute respiratory viral infections disrupt these interactions, thereby contributing to the pathogenesis of secondary bacterial infections.",2018 Nov 16,"['Hanada, Shigeo', 'Pirzadeh, Mina', 'Carver, Kyle Y.', 'Deng, Jane C.']",Front Immunol,,,False
aaaaf1da07387bece9bfca99582b31ebe33b1fbd,PMC,"Immunization of Experimental Dogs With Salivary Proteins From Lutzomyia longipalpis, Using DNA and Recombinant Canarypox Virus Induces Immune Responses Consistent With Protection Against Leishmania infantum",http://dx.doi.org/10.3389/fimmu.2018.02558,PMC6251279,30519235,CC BY,"Metacyclic Leishmania promastigotes are transmitted by sand flies that inject parasites and saliva into the host's skin. Previous studies have demonstrated that DNA plasmids encoding Lutzomyia longipalpis salivary proteins LJM17 and LJL143, when used to immunize dogs, resulted in a systemic and local Th1 cell-mediated immunity that interfered in parasite survival in vitro. Here we evaluated the ability of these same salivary antigens to induce anti-Leishmania immunity and to confer protection by immunizing dogs using a novel vaccination strategy more suitable for use in the field. The strategy consisted of a single dose of plasmid followed by two doses of recombinant Canarypoxvirus (rCanarypoxvirus) expressing L. longipalpis salivary proteins (LJM17 or LJL143). Thirty days after the final immunization, dogs were intradermally challenged with 10(7) Leishmania infantum promastigotes in the presence of L. longipalpis saliva. We followed the experimentally infected dogs for 10 months to characterize clinical, parasitological, and immunological parameters. Upon vaccination, all immunized dogs presented strong and specific humoral responses with increased serum concentrations of IFN-γ, TNF, IL-7, and IL-15. The serum of dogs immunized with LJM17 also exhibited high levels of IL-2, IL-6, and IL-18. L. infantum infection was established in all experimental groups as evidenced by the presence of anti-Leishmania IgG, and by parasite detection in the spleen and skin. Dogs immunized with LJM17-based vaccines presented higher circulating levels of IFN-γ, IL-2, IL-6, IL-7, IL-15, IL-18, TNF, CXCL10, and GM-CSF post-infection when compared with controls. Results demonstrated that relevant Leishmania-specific immune responses were induced following vaccination of dogs with L. longipalpis salivary antigen LJM17 administered in a single priming dose of plasmid DNA, followed by two booster doses of recombinant Canarypox vector. Importantly, a significant increase in pro-inflammatory cytokines and chemokines known to be relevant for protection against leishmaniasis was evidenced after challenging LJM17-vaccinated dogs as compared to controls. Although similar results were observed following immunization with LJL143, the pro-inflammatory response observed after immunization was attenuated following infection. Collectively, these data suggest that the LJM17-based vaccine induced an immune profile consistent with the expected protective immunity against canine leishmaniosis. These results clearly support the need for further evaluation of the LJM17 antigen, using a heterologous prime-boost vaccination strategy against canine visceral leishmaniosis (CVL).",2018 Nov 16,"['Abbehusen, Melissa Moura Costa', 'Cunha, Jurema', 'Suarez, Martha Sena', 'Teixeira, Clarissa', 'Almeida, Valter dos Anjos', 'Pereira, Laís da Silva', 'Bordoni, Marcelo', 'Gil-Santana, Leonardo', 'Solcà, Manuela da Silva', 'Fraga, Deborah Bittencourt Moté', 'Fischer, Laurent', 'Bozza, Patricia Torres', 'Veras, Patricia Sampaio Tavares', 'Valenzuela, Jesus G.', 'Kamhawi, Shaden', 'Andrade, Bruno B.', 'Brodskyn, Claudia I.']",Front Immunol,,,True
3d950119c81a03ac40e3d304f3fee12617a3316c,PMC,Translesion polymerase kappa-dependent DNA synthesis underlies replication fork recovery,http://dx.doi.org/10.7554/eLife.41426,PMC6251625,30422114,CC BY,"DNA replication stress is often defined by the slowing or stalling of replication fork progression leading to local or global DNA synthesis inhibition. Failure to resolve replication stress in a timely manner contribute toward cell cycle defects, genome instability and human disease; however, the mechanism for fork recovery remains poorly defined. Here, we show that the translesion DNA polymerase (Pol) kappa, a DinB orthologue, has a unique role in both protecting and restarting stalled replication forks under conditions of nucleotide deprivation. Importantly, Pol kappa-mediated DNA synthesis during hydroxyurea (HU)-dependent fork restart is regulated by both the Fanconi Anemia (FA) pathway and PCNA polyubiquitination. Loss of Pol kappa prevents timely rescue of stalled replication forks, leading to replication-associated genomic instability, and a p53-dependent cell cycle defect. Taken together, our results identify a previously unanticipated role for Pol kappa in promoting DNA synthesis and replication stress recovery at sites of stalled forks.",,"['Tonzi, Peter', 'Yin, Yandong', 'Lee, Chelsea Wei Ting', 'Rothenberg, Eli', 'Huang, Tony T']",eLife.; 7:e41426,,,True
916bd646b1fe224dfdda73b6b039922829b1f448,PMC,Translesion polymerase kappa-dependent DNA synthesis underlies replication fork recovery,http://dx.doi.org/10.7554/eLife.41426,PMC6251625,30422114,CC BY,"DNA replication stress is often defined by the slowing or stalling of replication fork progression leading to local or global DNA synthesis inhibition. Failure to resolve replication stress in a timely manner contribute toward cell cycle defects, genome instability and human disease; however, the mechanism for fork recovery remains poorly defined. Here, we show that the translesion DNA polymerase (Pol) kappa, a DinB orthologue, has a unique role in both protecting and restarting stalled replication forks under conditions of nucleotide deprivation. Importantly, Pol kappa-mediated DNA synthesis during hydroxyurea (HU)-dependent fork restart is regulated by both the Fanconi Anemia (FA) pathway and PCNA polyubiquitination. Loss of Pol kappa prevents timely rescue of stalled replication forks, leading to replication-associated genomic instability, and a p53-dependent cell cycle defect. Taken together, our results identify a previously unanticipated role for Pol kappa in promoting DNA synthesis and replication stress recovery at sites of stalled forks.",,"['Tonzi, Peter', 'Yin, Yandong', 'Lee, Chelsea Wei Ting', 'Rothenberg, Eli', 'Huang, Tony T']",eLife.; 7:e41426,,,False
6a0f4aac2dfa46df489b653a06df4b5036e452ea,PMC,Breaking Bad: How Viruses Subvert the Cell Cycle,http://dx.doi.org/10.3389/fcimb.2018.00396,PMC6252338,30510918,CC BY,"Interactions between the host and viruses during the course of their co-evolution have not only shaped cellular function and the immune system, but also the counter measures employed by viruses. Relatively small genomes and high replication rates allow viruses to accumulate mutations and continuously present the host with new challenges. It is therefore, no surprise that they either escape detection or modulate host physiology, often by redirecting normal cellular pathways to their own advantage. Viruses utilize a diverse array of strategies and molecular targets to subvert host cellular processes, while evading detection. These include cell-cycle regulation, major histocompatibility complex-restricted antigen presentation, intracellular protein transport, apoptosis, cytokine-mediated signaling, and humoral immune responses. Moreover, viruses routinely manipulate the host cell cycle to create a favorable environment for replication, largely by deregulating cell cycle checkpoints. This review focuses on our current understanding of the molecular aspects of cell cycle regulation that are often targeted by viruses. Further study of their interactions should provide fundamental insights into cell cycle regulation and improve our ability to exploit these viruses.",2018 Nov 19,"['Fan, Ying', 'Sanyal, Sumana', 'Bruzzone, Roberto']",Front Cell Infect Microbiol,,,True
9644dba679eaf2bd1ce6c96769f5be2aff16ee40,PMC,Beyond Type 1 Regulatory T Cells: Co-expression of LAG3 and CD49b in IL-10-Producing T Cell Lineages,http://dx.doi.org/10.3389/fimmu.2018.02625,PMC6252342,30510554,CC BY,"Type 1 regulatory CD4(+) T (Tr1) cells express high levels of the immunosuppressive cytokine IL-10 but not the master transcription factor Foxp3, and can suppress inflammation and promote immune tolerance. In order to identify and obtain viable Tr1 cells for research and clinical applications, co-expression of CD49b and LAG3 has been proposed as a unique surface signature for both human and mouse Tr1 cells. However, recent studies have revealed that this pattern of co-expression is dependent on the stimulating conditions and the differentiation stage of the CD4(+) T cells. Here, using an IL-10(GFP)/Foxp3(RFP) dual reporter transgenic murine model, we demonstrate that co-expression of CD49b and LAG3 is not restricted to the Foxp3(−) Tr1 cells, but is also observed in Foxp3(+) T regulatory (Treg) cells and CD8(+) T cells that produce IL-10. Our data indicate that IL-10-producing Tr1 cells, Treg cells and CD8(+) T cells are all capable of co-expressing LAG3 and CD49b in vitro following differentiation under IL-10-inducing conditions, and in vivo following pathogenic insult or infection in the pulmonary mucosa. Our findings urge caution in the use of LAG3/CD49b co-expression as sole markers to identify Tr1 cells, since it may mark IL-10-producing T cell lineages more broadly, including the Foxp3(−) Tr1 cells, Foxp3(+) Treg cells, and CD8(+) T cells.",2018 Nov 19,"['Huang, Weishan', 'Solouki, Sabrina', 'Carter, Chavez', 'Zheng, Song-Guo', 'August, Avery']",Front Immunol,,,True
318eb743359acf11f860f81255d3a1625f33e484,PMC,Synthesis and Evaluation of Non-peptidic Cysteine Protease Inhibitors of P. falciparum Derived from Etacrynic Acid,http://dx.doi.org/10.3390/molecules14010019,PMC6253875,19104483,CC BY,"A series of etacrynic acid derivatives was synthesized and screened for their in vitro activity against Plasmodium falciparum, as well as their activity against recombinantly expressed falcipain-2 and -3. The two most active compounds of the series displayed IC(50) values of 9.0 and 18.8 μM against Plasmodia.",2008 Dec 23,"['Dude, Marie-Adrienne', 'Kaeppler, Ulrich', 'Herb, Monika', 'Schiller, Markus', 'Schulz, Franziska', 'Vedder, Birgit', 'Heppner, Saskia', 'Pradel, Gabriele', 'Gut, Jiri', 'Rosenthal, Philip J.', 'Schirmeister, Tanja', 'Leippe, Matthias', 'Gelhaus, Christoph']",Molecules,,,True
c64a088496e159b12a097a0c22a795a656aad07a,PMC,"Synthesis of 2,3-Dioxo-5-(substituted)arylpyrroles and Their 2-Oxo-5-aryl-3-hydrazone Pyrrolidine Derivatives",http://dx.doi.org/10.3390/molecules14010250,PMC6253891,19136912,CC BY,"Some novel 2,3-dioxo-5-(substituted)arylpyrroles have been synthesized. Among these, pyrrolidine compound 1b was converted to 2,3-dioxo-5-aryl pyrrolidine 2b. Finally a set of hydrazone derivatives was obtained from the reaction of 2b with various hydrazine salts. The structures of all the new synthesized compounds were confirmed by elemental analyses, IR and (1)H-NMR spectra.",2009 Jan 7,"['Mohammat, M.F.', 'Shaameri, Z.', 'Hamzah, A.S.']",Molecules,,,True
90b225bb89b9c6cd53621102fb383cf4fa090891,PMC,Gene Knockdowns in Adult Animals: PPMOs and Vivo-Morpholinos,http://dx.doi.org/10.3390/molecules14031304,PMC6253989,19325525,CC BY,"Antisense molecules do not readily cross cell membranes. This has limited the use of antisense to systems where techniques have been worked out to introduce the molecules into cells, such as embryos and cell cultures. Uncharged antisense bearing a group of guanidinium moieties on either a linear peptide or dendrimer scaffold can enter cells by endocytosis and subsequently escape from endosomes into the cytosol/nuclear compartment of cells. These technologies allow systemic administration of antisense, making gene knockdowns and splice modification feasible in adult animals; this review presents examples of such animal studies. Techniques developed with PPMOs, which are an arginine-rich cell-penetrating peptide linked to a Morpholino oligo, can also be performed using commercially available Vivo-Morpholinos, which are eight guanidinium groups on a dendrimeric scaffold linked to a Morpholino oligo. Antisense-based techniques such as blocking translation, modifying pre-mRNA splicing, inhibiting miRNA maturation and inhibiting viral replication can be conveniently applied in adult animals by injecting PPMOs or Vivo-Morpholinos.",2009 Mar 25,"['Moulton, Jon D.', 'Jiang, Shan']",Molecules,,,True
6d5600b0c8725f08c005efaaf90fe3668aef1c65,PMC,Delivery of IL-35 by Lactococcus lactis Ameliorates Collagen-Induced Arthritis in Mice,http://dx.doi.org/10.3389/fimmu.2018.02691,PMC6255909,30515168,CC BY,"IL-35, a relatively newly discovered cytokine belonging to the larger IL-12 family, shows unique anti-inflammatory properties, believed to be associated with dedicated receptors and signaling pathways. IL-35 plays a pivotal role in the development and the function of both regulatory B (Bregs) and T cells (Tregs). In order to further its therapeutic potential, a dairy Lactococcus lactis strain was engineered to express murine IL-35 (LL-IL35), and this recombinant strain was applied to suppress collagen-induced arthritis (CIA). Oral administration of LL-IL35 effectively reduced the incidence and disease severity of CIA. When administered therapeutically, LL-IL35 abruptly halted CIA progression with no increase in disease severity by reducing neutrophil influx into the joints. LL-IL35 treatment reduced IFN-γ and IL-17 3.7- and 8.5-fold, respectively, and increased IL-10 production compared to diseased mice. Foxp3(+) and Foxp3(−) CD39(+) CD4(+) T cells were previously shown to be the Tregs responsible for conferring protection against CIA. Inquiry into their induction revealed that both CCR6(+) and CCR6(−) Foxp3(+or−) CD39(+) CD4(+) T cells act as the source of the IL-10 induced by LL-IL35. Thus, this study demonstrates the feasibility and benefits of engineered probiotics for treating autoimmune diseases.",2018 Nov 20,"['Maddaloni, Massimo', 'Kochetkova, Irina', 'Hoffman, Carol', 'Pascual, David W.']",Front Immunol,,,True
042c9d15e000e5ea7b91612b4c10175e88112278,PMC,Complete Genome Sequence of Avian Coronavirus Strain D274,http://dx.doi.org/10.1128/MRA.01003-18,PMC6256507,30533915,CC BY,"Avian coronavirus, the causative agent of avian infectious bronchitis, occurs as multiple genotypes and lineages, and full genomes are not available for the majority of them. This paper reports the (previously unknown) complete genome sequence of strain D274 of this virus (27,599 nucleotides), isolated from chickens in The Netherlands in 1979.",2018 Aug 30,"['Brandão, Paulo E.', 'Hora, Aline S.', 'Silva, Sheila O. S.', 'Berg, Mikael', 'Taniwaki, Sueli A.']",Microbiol Resour Announc,,,True
b4977e3f26125c15ddb66fbfc8515e08ad166bf0,PMC,Complete Genome Sequences of Four Major Viruses Infecting Marine Shrimp in Egypt,http://dx.doi.org/10.1128/MRA.00809-18,PMC6256532,30533940,CC BY,"The genome sequences of four economically important shrimp viruses, Penaeus stylirostris densovirus 1, hepatopancreatic parvovirus, yellow head virus, and gill-associated virus, are reported here. Genome data are fundamental for epidemiological studies in determining the origins of these viruses detected for the first time in Egypt and in developing disease management strategies.",2018 Sep 6,"['Megahed, Mohamed E.', 'Cruz-Flores, Roberto', 'Dhar, Arun K.']",Microbiol Resour Announc,,,True
0539cdf9c5215f7d1f53d1cb7af556ba1f799937,PMC,Detection of HIV cDNA Point Mutations with Rolling-Circle Amplification Arrays,http://dx.doi.org/10.3390/molecules15020619,PMC6256933,20335932,CC BY,"In this paper we describe an isothermal rolling-circle amplification (RCA) protocol to detect gene point mutations on chips. The method is based on an allele-specific oligonucleotide circularization mediated by a special DNA ligase. The probe is circularized when perfect complementary sequences between the probe oligonucleotide and HIV cDNA gene. Mismatches around the ligation site can prevent probe circularization. The circularized probe (C-probe) can be amplified by rolling circle amplification to generate multimeric singlestranded DNA (ssDNA) under isothermal conditions. There are four sequence regions to bind respectively with fluorescent probe, RCA primer, solid probe and HIV cDNA template in the C-probe which we designed. These ssDNA products are hybridized with fluorescent probes and solid probes which are immobilized on a glass slide composing a regular microarray pattern. The fluorescence signals can be monitored by a scanner in the presence of HIV cDNA templates, whereas the probes cannot be circularized and signal of fluorescence cannot be found. The RCA array has capability of high-throughput detection of the point mutation and the single-nucleotide polymorphism (SNP). The development of C-probe-based technologies offers a promising prospect for situ detection, microarray, molecular diagnosis, single nucleotide polymorphism, and whole genome amplification.",2010 Jan 27,"['Wu, Lingwei', 'Liu, Quanjun', 'Wu, Zhongwei', 'Lu, Zuhong']",Molecules,,,True
ddbf9291a1a1cd15d61bcb6cd1946813251ba5cd,PMC,In Vitro and Ex Vivo Selection Procedures for Identifying Potentially Therapeutic DNA and RNA Molecules,http://dx.doi.org/10.3390/molecules15074610,PMC6257598,20657381,CC BY,"It was only relatively recently discovered that nucleic acids participate in a variety of biological functions, besides the storage and transmission of genetic information. Quite apart from the nucleotide sequence, it is now clear that the structure of a nucleic acid plays an essential role in its functionality, enabling catalysis and specific binding reactions. In vitro selection and evolution strategies have been extremely useful in the analysis of functional RNA and DNA molecules, helping to expand our knowledge of their functional repertoire and to identify and optimize DNA and RNA molecules with potential therapeutic and diagnostic applications. The great progress made in this field has prompted the development of ex vivo methods for selecting functional nucleic acids in the cellular environment. This review summarizes the most important and most recent applications of in vitro and ex vivo selection strategies aimed at exploring the therapeutic potential of nucleic acids.",2010 Jun 28,"['Marton, Soledad', 'Reyes-Darias, José A.', 'Sánchez-Luque, Francisco J.', 'Romero-López, Cristina', 'Berzal-Herranz, Alfredo']",Molecules,,,True
918502b9ff6b04705babfc9e08f9b0f7c7ece9cc,PMC,Retention strategies in longitudinal cohort studies: a systematic review and meta-analysis,http://dx.doi.org/10.1186/s12874-018-0586-7,PMC6258319,30477443,CC BY,"BACKGROUND: Participant retention strategies that minimise attrition in longitudinal cohort studies have evolved considerably in recent years. This study aimed to assess, via systematic review and meta-analysis, the effectiveness of both traditional strategies and contemporary innovations for retention adopted by longitudinal cohort studies in the past decade. METHODS: Health research databases were searched for retention strategies used within longitudinal cohort studies published in the 10-years prior, with 143 eligible longitudinal cohort studies identified (141 articles; sample size range: 30 to 61,895). Details on retention strategies and rates, research designs, and participant demographics were extracted. Meta-analyses of retained proportions were performed to examine the association between cohort retention rate and individual and thematically grouped retention strategies. RESULTS: Results identified 95 retention strategies, broadly classed as either: barrier-reduction, community-building, follow-up/reminder, or tracing strategies. Forty-four of these strategies had not been identified in previous reviews. Meta-regressions indicated that studies using barrier-reduction strategies retained 10% more of their sample (95%CI [0.13 to 1.08]; p = .01); however, studies using follow-up/reminder strategies lost an additional 10% of their sample (95%CI [− 1.19 to − 0.21]; p = .02). The overall number of strategies employed was not associated with retention. CONCLUSIONS: Employing a larger number of retention strategies may not be associated with improved retention in longitudinal cohort studies, contrary to earlier narrative reviews. Results suggest that strategies that aim to reduce participant burden (e.g., flexibility in data collection methods) might be most effective in maximising cohort retention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12874-018-0586-7) contains supplementary material, which is available to authorized users.",2018 Nov 26,"['Teague, Samantha', 'Youssef, George J.', 'Macdonald, Jacqui A.', 'Sciberras, Emma', 'Shatte, Adrian', 'Fuller-Tyszkiewicz, Matthew', 'Greenwood, Chris', 'McIntosh, Jennifer', 'Olsson, Craig A.', 'Hutchinson, Delyse', None]",BMC Med Res Methodol,,,True
f625d4a9a3a6e1dad4c03e5e79e04b3e6b098997,PMC,"Detection of distinct MERS-Coronavirus strains in dromedary camels from Kenya, 2017",http://dx.doi.org/10.1038/s41426-018-0193-z,PMC6258726,30482895,CC BY,,2018 Nov 28,"['Kiambi, Stella', 'Corman, Victor M.', 'Sitawa, Rina', 'Githinji, Jane', 'Ngoci, James', 'Ozomata, Abdullahi S.', 'Gardner, Emma', 'von Dobschuetz, Sophie', 'Morzaria, Subhash', 'Kimutai, Joshua', 'Schroeder, Simon', 'Njagi, Obadiah', 'Simpkin, Piers', 'Rugalema, Gabriel', 'Tadesse, Zelalem', 'Lubroth, Juan', 'Makonnen, Yilma', 'Drosten, Christian', 'Müller, Marcel A.', 'Fasina, Folorunso O.']",Emerg Microbes Infect,,,True
caf95fa590e7cbb34e10314bfd93beb44e35caab,PMC,Morbidity and Mortality Associated With Respiratory Virus Infections in Allogeneic Hematopoietic Cell Transplant: Too Little Defense or Harmful Immunity?,http://dx.doi.org/10.3389/fmicb.2018.02795,PMC6258814,30519222,CC BY,"The impact on morbidity and mortality of Community Acquired Respiratory Virus (CARV) infections in patients undergoing Allogeneic Hematopoietic Cell Transplant (HCT) is widely studied. Here we give an overview of the current literature on the incidence and chance of progression to severe disease in this highly immune compromised population. We discuss the issue whether it is predominantly direct viral damage that causes clinical deterioration, or that it is in fact the allogeneic immuneresponse to the virus that is most important. This is an important question as it will guide therapeutic decision making. It asks for further collaborative studies focusing on sensitive surveillance with PCR techniques and relating clinical data with parameters of immune reconstitution.",2018 Nov 21,"['Versluys, Anne Birgitta', 'Boelens, Jaap Jan']",Front Microbiol,,,True
68ca53b6414e682661c4decd41eb9ff00574d862,PMC,Targeting of the Nasal Mucosa by Japanese Encephalitis Virus for Non-Vector-Borne Transmission,http://dx.doi.org/10.1128/JVI.01091-18,PMC6258954,30282716,CC BY,"The mosquito-borne Japanese encephalitis virus (JEV) causes severe central nervous system diseases and cycles between Culex mosquitoes and different vertebrates. For JEV and some other flaviviruses, oronasal transmission is described, but the mode of infection is unknown. Using nasal mucosal tissue explants and primary porcine nasal epithelial cells (NEC) at the air-liquid interface (ALI) and macrophages as ex vivo and in vitro models, we determined that the nasal epithelium could represent the route of entry and exit for JEV in pigs. Porcine NEC at the ALI exposed to with JEV resulted in apical and basolateral virus shedding and release of monocyte recruiting chemokines, indicating infection and replication in macrophages. Moreover, macrophages stimulated by alarmins, including interleukin-25, interleukin-33, and thymic stromal lymphopoietin, were more permissive to the JEV infection. Altogether, our data are important to understand the mechanism of non-vector-borne direct transmission of Japanese encephalitis virus in pigs. IMPORTANCE JEV, a main cause of severe viral encephalitis in humans, has a complex ecology composed of a mosquito-waterbird cycle and a cycle involving pigs, which amplifies virus transmission to mosquitoes, leading to increased human cases. JEV can be transmitted between pigs by contact in the absence of arthropod vectors. Moreover, virus or viral RNA is found in oronasal secretions and the nasal epithelium. Using nasal mucosa tissue explants and three-dimensional porcine nasal epithelial cells cultures and macrophages as ex vivo and in vitro models, we determined that the nasal epithelium could be a route of entry as well as exit for the virus. Infection of nasal epithelial cells resulted in apical and basolateral virus shedding and release of monocyte recruiting chemokines and therefore infection and replication in macrophages, which is favored by epithelial-cell-derived cytokines. The results are relevant to understand the mechanism of non-vector-borne direct transmission of JEV.",2018 Nov 27,"['García-Nicolás, Obdulio', 'Braun, Roman O.', 'Milona, Panagiota', 'Lewandowska, Marta', 'Dijkman, Ronald', 'Alves, Marco P.', 'Summerfield, Artur']",J Virol,,,True
e1371bc7c700d3752ae645755967db504347d87f,PMC,Bioinformatics Resources and Tools for Phage Display,http://dx.doi.org/10.3390/molecules16010694,PMC6259106,21245805,CC BY,"Databases and computational tools for mimotopes have been an important part of phage display study. Five special databases and eighteen algorithms, programs and web servers and their applications are reviewed in this paper. Although these bioinformatics resources have been widely used to exclude target-unrelated peptides, characterize small molecules-protein interactions and map protein-protein interactions, a lot of problems are still waiting to be solved. With the improvement of these tools, they are expected to serve the phage display community better.",2011 Jan 18,"['Huang, Jian', 'Ru, Beibei', 'Dai, Ping']",Molecules,,,True
c27cd721cc62f4294aeb0159e587efb9391ce8ad,PMC,Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review,http://dx.doi.org/10.3390/molecules15129252,PMC6259136,21160452,CC BY,"Essential oils are complex mixtures isolated from aromatic plants which may possess antioxidant and anti-inflammatory activities of interest in thye food and cosmetic industries as well as in the human health field. In this work, a review was done on the most recent publications concerning their antioxidant and anti-inflammatory activities. At the same time a survey of the methods generally used for the evaluation of antioxidant activity and some of the mechanisms involved in the anti-inflammatory activities of essential oils are also reported.",2010 Dec 15,"Miguel, Maria Graça",Molecules,,,True
d3f7f0af7fceb8d73489863fca4c5ebb608f6fd4,PMC,Small Interfering RNA Effectively Inhibits the Expression of SARS Coronavirus Membrane Gene at Two Novel Targeting Sites,http://dx.doi.org/10.3390/molecules15107197,PMC6259191,20956884,CC BY,"Small interfering RNA (siRNA) is a class of duplex RNA molecules of 21-25 nt nucleotides in length functioning post-transcriptionally to downregulate targeted gene expression. The membrane (M) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is highly abundant during viral infections and is a critical element for viral assembly. Nucleotide substitution in the viral genome occurs frequently during SARS-CoV infection. In the current study, we analyzed the M gene sequences derived from 15 SARS-CoV isolates and uncovered six nucleotide substitutions among these isolates. Interestingly, these nucleotide substitutions are all located at the 5’ half of the M gene. Based on this information and previous reports, we created two novel siRNAs targeting two unexplored and well conserved regions in the M gene. The effects of these two siRNAs were tested by semi-quantitative RT-PCR and EGFP-M fusion gene expression. The results demonstrated that both siRNAs effectively and specifically blocked the targeted gene expression. Real time quantitative RT-PCR (qRT-PCR) revealed that siRNA targeting the 3’ half of the M gene (si-M2) induced more potent inhibition than that targeting the 5’ half (si-M1). Both si-M1 and si-M2 significantly downregulated M gene mediated upregulation of interferon β expression. Thus, our results indicate that SARS-CoV M gene specific siRNA might function in a sequence-dependent manner.",2010 Oct 18,"['Wang, Ying', 'Cao, Ying-Li', 'Yang, Fan', 'Zhang, Yun', 'Wang, Shu-Hui', 'Liu, Li']",Molecules,,,True
a6943ae5bcdb965103926179b2a31a77312790e2,PMC,"Anti-Neoplastic Effects of Gallic Acid, a Major Component of Toona sinensis Leaf Extract, on Oral Squamous Carcinoma Cells",http://dx.doi.org/10.3390/molecules15118377,PMC6259246,21081858,CC BY,"Extract of Toona sinensis (TS) has been reported to have various effects on cultured cell lines, including anti-proliferative activity in cancer cells. We have studied the effects of TS on various human oral squamous carcinoma cell lines (HOSCC), including UM1, UM2, SCC-4, and SCC-9. These cell lines were treated with TS leaf extract and screened for viability, apoptosis, necrosis, and apoptotic gene expression. Normal human oral keratinocytes (NHOK) served as a control for cytotoxic assays. Viability of TS-treated HOSCC was reduced, whereas that of NHOK was not affected. FACScan analysis revealed that the leaf extract induced apoptosis or a combination of apoptosis and necrosis, depending on cell type. Microarray and semi-quantitative RT-PCR analysis for apoptotic-related gene expression revealed that 3,4,5-trihydroxybenzoic acid (gallic acid, one of the major bioactive compounds purified from TS extract) up-regulated pro-apoptotic genes such TNF-α, TP53BP2, and GADD45A, and down-regulated the anti-apoptotic genes Survivin and cIAP1, resulting in cell death. This study suggests that gallic acid, the major bioactive compound present, is responsible for the anti-neoplastic effect of Toona sinensis leaf extract.",2010 Nov 16,"['Chia, Yi-Chen', 'Rajbanshi, Ranjan', 'Calhoun, Colonya', 'Chiu, Robert H.']",Molecules,,,True
342160459c20d71ef6f3da97763dd855a5357b1e,PMC,Targeting Cell Entry of Enveloped Viruses as an Antiviral Strategy,http://dx.doi.org/10.3390/molecules16010221,PMC6259279,21193846,CC BY,"The entry of enveloped viruses into their host cells involves several successive steps, each one being amenable to therapeutic intervention. Entry inhibitors act by targeting viral and/or cellular components, through either the inhibition of protein-protein interactions within the viral envelope proteins or between viral proteins and host cell receptors, or through the inhibition of protein-lipid interactions. Interestingly, inhibitors that concentrate into/onto the membrane in order to target a protein involved in the entry process, such as arbidol or peptide inhibitors of the human immunodeficiency virus (HIV), could allow the use of doses compatible with therapeutic requirements. The efficacy of these drugs validates entry as a point of intervention in viral life cycles. Strategies based upon small molecule antiviral agents, peptides, proteins or nucleic acids, would most likely prove efficient in multidrug combinations, in order to inhibit several steps of virus life cycle and prevent disease progression.",2010 Dec 30,"['Teissier, Elodie', 'Penin, François', 'Pécheur, Eve-Isabelle']",Molecules,,,True
4c3ff586d4238ccd7324950db31a02037463f973,PMC,Comparative Anti-Infectious Bronchitis Virus (IBV) Activity of (-)-Pinene: Effect on Nucleocapsid (N) Protein,http://dx.doi.org/10.3390/molecules16021044,PMC6259611,21350392,CC BY,"In the present study, anti-IBV (infectious bronchitis virus) activities of (-)-pinenes were studied by MTT assay, as well as docking and molecular dynamic (MD) simulations. The CC(50)values of (-)-α-pinene and (-)-β-pinene were above 10 mM. And the maximum noncytotoxic concentrations (TD(0)) of (-)-α-pinene and (-)-β-pinene were determined as 7.88 ± 0.06 and 6.09 ± 0.31 mM, respectively. The two compounds were found to inhibit IBV with an IC(50) of 0.98 ± 0.25 and 1.32 ± 0.11 mM. The MTT assay showed that the inhibitions of (-)-pinenes against IBV appear to occur moderately before entering the cell but are much stronger occur after penetration of the virus into the cell. Molecular simulations indicated that (-)-α-pinene and (-)-β-pinene specifically interact with the active site which is located at the N terminus of phosphorylated nucleocapsid (N) protein, with the former being more potent than the latter. The binding energies of them are −36.83 and −35.59 kcal mol(−1), respectively. Results presented here may suggest that (-)-α-pinene and (-)-β-pinene possess anti-IBV properties, and therefore are a potential source of anti-IBV ingredients for the pharmaceutical industry.",2011 Jan 25,"['Yang, Zhiwei', 'Wu, Nan', 'Zu, Yuangang', 'Fu, Yujie']",Molecules,,,True
a765ae8d7eae55875cb832428c9082a6e4e4ae82,PMC,Identification and Characterization of Three Novel Small Interference RNAs That Effectively Down-Regulate the Isolated Nucleocapsid Gene Expression of SARS Coronavirus,http://dx.doi.org/10.3390/molecules16021544,PMC6259856,21317844,CC BY,"Nucleocapsid (N) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is a major pathological determinant in the host that may cause host cell apoptosis, upregulate the proinflammatory cytokine production, and block innate immune responses. Therefore, N gene has long been thought an ideal target for the design of small interference RNA (siRNA). siRNA is a class of small non-coding RNAs with a size of 21-25nt that functions post-transcriptionally to block targeted gene expression. In this study, we analyzed the N gene coding sequences derived from 16 different isolates, and found that nucleotide deletions and substitutions are mainly located at the first 440nt sequence. Combining previous reports and the above sequence information, we create three novel siRNAs that specifically target the conserved and unexploited regions in the N gene. We show that these siRNAs could effectively and specifically block the isolated N gene expression in mammal cells. Furthermore, we provide evidence to show that N gene can effectively up-regulate M gene mediated interferon β (IFNβ) production, while blocking N gene expression by specific siRNA significantly reduces IFNβ gene expression. Our data indicate that the inhibitory effect of siRNA on the isolated N gene expression might be influenced by the sequence context around the targeted sites.",2011 Feb 11,"['Cao, Ying-Li', 'Wang, Ying', 'Guo, Rong', 'Yang, Fan', 'Zhang, Yun', 'Wang, Shu-Hui', 'Liu, Li']",Molecules,,,True
e51146b66f1894acaf65626acab69810a1394a86,PMC,The role of the hotel industry in the response to emerging epidemics: a case study of SARS in 2003 and H1N1 swine flu in 2009 in Hong Kong,http://dx.doi.org/10.1186/s12992-018-0438-6,PMC6260697,30482214,CC BY,"BACKGROUND: The global travel and tourism industry has been rapidly expanding in the past decades. The traditional focus on border screening, and by airline and cruise industries may be inadequate due to the incubation period of an infectious disease. This case study highlights the potential role of the hotel industry in epidemic preparedness and response. METHODS: This case study focuses on the epidemic outbreaks of SARS in 2003 and H1N1 swine flu in 2009 in Hong Kong, and the subsequent guidelines published by the health authority in relation to the hotel industry in Hong Kong which provide the backbone for discussion. RESULTS: The Metropole Hotel hastened the international spread of the 2003 SARS outbreak by the index case infecting visitors from Singapore, Vietnam, Canada as well as local people via close contact with the index case and the environmental contamination. The one-week quarantine of more than 300 guests and staff at the Metropark Hotel during the 2009 H1N1 swine flu exposed gaps in the partnership with the hotel industry. The subsequent guidelines for the hotel industry from the Centre of Health Protection focused largely on the maintenance of hygiene within the hotel premises. CONCLUSION: Positive collaborations may bring about effective preparedness across the health and the tourism sectors for future epidemics. Regular hygiene surveillance at hotel facilities, and developing coordination mechanism for impending epidemics on the use of screening, swift reporting and isolation of infected persons may help mitigate the impact of future events. Preparedness and contingency plans for infectious disease control for the hotel industry requires continuous engagement and dialogue.",2018 Nov 27,"['Hung, Kevin K. C.', 'Mark, Carman K. M.', 'Yeung, May P. S.', 'Chan, Emily Y. Y.', 'Graham, Colin A.']",Global Health,,,True
b6019e4fafd2bf05e5f46bef590141a2f115c4c9,PMC,Commentary: Phyllostomid bat microbiome composition is associated to host phylogeny and feeding strategies,http://dx.doi.org/10.3389/fmicb.2018.02863,PMC6262150,30524418,CC BY,,2018 Nov 22,"['Banerjee, Arinjay', 'Pérez-López, Edel', 'Mossman, Karen']",Front Microbiol,,,True
74d9ff6a1e0b0d53a989aa00d2eddfd3d4f4dbd5,PMC,Linkages between Chiropteran diversity and ecosystem services for sustainable fragmented forest conservation,http://dx.doi.org/10.1016/j.dib.2018.11.058,PMC6262155,30533456,CC BY,"This data article informs about Chiropteran diversity, new records, ecosystem services and possible pathogen carriers in fragmented forests (sub-divided by utility corridors, man-made structures, untouched and secondary plantations) within districts Setiu (Setiu Research Station), Hulu Terengganu (Saok and Lasir waterfalls) and Besut (Gunung Tebu Forest Reserve) of state Terengganu, Peninsular Malaysia. These bats were captured using harp traps and mist nets that were set 10 m apart across flyways, streams and less cluttered trees in the 50 m × 50 m transect zones (identified at each site). All animals were distinguished by morphology and gender before their release at the site of capture. The data comprise of five bat family groups Hipposideridae, Megadermatidae, Pteropodidae, Rhinolophidae and Vespertilionidae. It is interesting to note that untouched Saok Waterfalls is home to wide variety of bats listed (68.8%), followed by secondary forests of Gunung Tebu Forest Reserve (24.8%), untouched Lasir Waterfalls (4.8%) and lastly, Setiu Research Station as least favored (1.6%). Chiroptera like Cynopterus brachyotis (n = 23, 37.7%), Hipposideros bicolor (n = 6, 9.8%) and Scotophilus kuhli (n = 6, 9.8%) were most dominant in the checklist whereas Hipposideros armiger, Murina suilla and Scotophilus kuhlii are new data records in the fragmented forests of Terengganu. The data were interpret into Shannon, Simpson, Margalef, Menhinik and Evenness indices to individually or collectively distinguish chiropteran variety in Terengganu State whereas weight-forearm length (W/FA) informs about chiropteran Body Condition Index (-0.25 to 0.25). The function of bats were also identified to distinguish service providers (pollination and forests regeneration) and zoonotic pathogen carriers (in particular to Leptospira bacteria, Nipah virus and Sindbis virus).",2018 Nov 14,"['Fakhrul-Hatta, Siti Nurfatiha Najihah', 'Nelson, Bryan Raveen', 'Shafie, Nur Juliani', 'Zahidin, Muhamad Aidil', 'Abdullah, Mohd. Tajuddin']",Data Brief,,,False
36de1c611ceee1af5ceddea2e4041691829cf7ef,PMC,The Hepatitis C Virus-Induced Membranous Web in Liver Tissue,http://dx.doi.org/10.3390/cells7110191,PMC6262270,30388825,CC BY,"Host cell membrane rearrangements induced by the hepatitis C virus (HCV) have been exclusively studied in vitro. These studies have shown that HCV induces double-membrane vesicles (DMVs), which probably serve to separate replication sites from the cytoplasmic sensors of the innate immune response. We report for the first time the observation of HCV-induced membrane rearrangements in liver biopsy specimens from patients chronically infected with HCV. Unlike observations performed in vitro, the membranous web detected in liver tissue seems essentially made of clusters of single-membrane vesicles derived from the endoplasmic reticulum and close to lipid droplets. This suggests that the DMVs could be a hallmark of laboratory-adapted HCV strains, possibly due to their ability to achieve a high level of replication. Alternatively, the concealment of viral RNA in DMVs may be part of innate immune response mechanisms particularly developed in hepatoma cell lines cultured in vitro. In any case, this constitutes the first report showing the differences in the membranous web established by HCV in vitro and in vivo.",2018 Nov 1,"['Blanchard, Emmanuelle', 'Roingeard, Philippe']",Cells,,,True
fb9e05516efdae3600796552393fd3e3c26cb3d5,PMC,An Inverse Relationship between Hyperuricemia and Mortality in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis,http://dx.doi.org/10.3390/jcm7110416,PMC6262420,30400636,CC BY,"Background: The results have been inconsistent with regards to the impact of uric acid (UA) on clinical outcomes both in the general population and in patients with chronic kidney disease. The aim of this study was to study the influence of serum UA levels on mortality in patients undergoing continuous ambulatory peritoneal dialysis. Methods: Data on 492 patients from a single peritoneal dialysis unit were retrospectively analyzed. The mean age of the patients was 53.5 ± 15.3 years, with 52% being female (n = 255). The concomitant comorbidities at the start of continuous ambulatory peritoneal dialysis (CAPD) encompassed diabetes mellitus (n = 179, 34.6%), hypertension (n = 419, 85.2%), and cardiovascular disease (n = 186, 37.9%). The study cohort was divided into sex-specific tertiles according to baseline UA level. A Cox proportional hazard model was used to calculate hazard ratios (HRs) of all-cause, cardiovascular, and infection-associated mortality with adjustments for demographic and laboratory data, medications, and comorbidities. Results: Multivariate Cox regression analysis showed that, using UA tertile 1 as the reference, the adjusted HR of all-cause, cardiovascular, and infection-associated mortality for tertile 3 was 0.4 (95% confidence interval (CI) 0.24–0.68, p = 0.001), 0.4 (95% CI 0.2–0.81, p = 0.01), and 0.47 (95% CI 0.19–1.08, p = 0.1). In the fully adjusted model, the adjusted HRs of all-cause, cardiovascular, and infection-associated mortality for each 1-mg/dL increase in UA level were 0.84 (95% CI, 0.69–0.9, p = 0.07), 0.79 (95% CI, 0.61–1.01, p = 0.06), and 0.79 (95% CI, 0.48–1.21, p = 0.32) for men and 0.57 (95% CI, 0.44–0.73, p < 0.001), 0.6 (95% CI, 0.41–0.87, p = 0.006), and 0.41 (95% CI, 0.26–0.6, p < 0.001) for women, respectively. Conclusions: Higher UA levels are associated with lower risks of all-cause, cardiovascular and infection-associated mortality in women treated with continuous ambulatory peritoneal dialysis.",2018 Nov 5,"['Lai, Kuan-Ju', 'Kor, Chew-Teng', 'Hsieh, Yao-Peng']",J Clin Med,,,True
185b7ddc439bc3490a0c97ecc00861497c6bd481,PMC,Lack of LTβR Increases Susceptibility of IPEC-J2 Cells to Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.3390/cells7110222,PMC6262443,30469426,CC BY,"The essential requirement of the lymphotoxin beta receptor (LTβR) in the development and maintenance of peripheral lymphoid organs is well recognized. Evidence shows that LTβR is involved in various cellular processes; however, whether it plays a role in maintaining the cellular function of intestinal porcine enterocytes (IPEC-J2), specifically during porcine epidemic diarrhea virus (PEDV) infection, remains unknown. In this study, we generated LTβR null IPEC-J2 cells using CRISPR/Cas9 to examine the importance of LTβR in cell proliferation, apoptosis, and the response to PEDV infection. Our results showed that the lack of LTβR leads to significantly decreased cell proliferation, potentially due to S phase arrest in LTβR(−/−) IPEC-J2 cells. Label-free digital holographic microscopy was used to record the three-dimensional morphology of both cell types for up to 72 hours and revealed significantly increased numbers of LTβR(−/−) cells undergoing apoptosis. Furthermore, we found that PEDV-infected LTβR(−/−) null IPEC-J2 cells exhibited significant suppression of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) target genes (interleukin (IL)-6 and IL-8) and mucosal barrier integrity-related genes (vascular cell adhesion molecule 1 (VCAM1) and IL-22), which may explain why LTβR(−/−) cells are more susceptible to PEDV infection. Collectively, our data not only demonstrate the key role of LTβR in intestinal porcine enterocytes, but also provide data for the improved understanding of the cellular response to PEDV infection.",2018 Nov 21,"['Altawaty, Tawfeek', 'Liu, Lulu', 'Zhang, Hongyong', 'Tao, Cong', 'Hou, Shaohua', 'Li, Kui', 'Wang, Yanfang']",Cells,,,True
db1fddccdec7aba24d1f303986814660508f3806,PMC,Lack of LTβR Increases Susceptibility of IPEC-J2 Cells to Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.3390/cells7110222,PMC6262443,30469426,CC BY,"The essential requirement of the lymphotoxin beta receptor (LTβR) in the development and maintenance of peripheral lymphoid organs is well recognized. Evidence shows that LTβR is involved in various cellular processes; however, whether it plays a role in maintaining the cellular function of intestinal porcine enterocytes (IPEC-J2), specifically during porcine epidemic diarrhea virus (PEDV) infection, remains unknown. In this study, we generated LTβR null IPEC-J2 cells using CRISPR/Cas9 to examine the importance of LTβR in cell proliferation, apoptosis, and the response to PEDV infection. Our results showed that the lack of LTβR leads to significantly decreased cell proliferation, potentially due to S phase arrest in LTβR(−/−) IPEC-J2 cells. Label-free digital holographic microscopy was used to record the three-dimensional morphology of both cell types for up to 72 hours and revealed significantly increased numbers of LTβR(−/−) cells undergoing apoptosis. Furthermore, we found that PEDV-infected LTβR(−/−) null IPEC-J2 cells exhibited significant suppression of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) target genes (interleukin (IL)-6 and IL-8) and mucosal barrier integrity-related genes (vascular cell adhesion molecule 1 (VCAM1) and IL-22), which may explain why LTβR(−/−) cells are more susceptible to PEDV infection. Collectively, our data not only demonstrate the key role of LTβR in intestinal porcine enterocytes, but also provide data for the improved understanding of the cellular response to PEDV infection.",2018 Nov 21,"['Altawaty, Tawfeek', 'Liu, Lulu', 'Zhang, Hongyong', 'Tao, Cong', 'Hou, Shaohua', 'Li, Kui', 'Wang, Yanfang']",Cells,,,False
fa0630536ffb3bc1d387a3bfea810be65fd6f950,PMC,Pharmacological and Biological Antiviral Therapeutics for Cardiac Coxsackievirus Infections,http://dx.doi.org/10.3390/molecules16108475,PMC6264230,21989310,CC BY,"Subtype B coxsackieviruses (CVB) represent the most commonly identified infectious agents associated with acute and chronic myocarditis, with CVB3 being the most common variant. Damage to the heart is induced both directly by virally mediated cell destruction and indirectly due to the immune and autoimmune processes reacting to virus infection. This review addresses antiviral therapeutics for cardiac coxsackievirus infections discovered over the last 25 years. One group represents pharmacologically active low molecular weight substances that inhibit virus uptake by binding to the virus capsid (e.g., pleconaril) or inactivate viral proteins (e.g., NO-metoprolol and ribavirin) or inhibit cellular proteins which are essential for viral replication (e.g., ubiquitination inhibitors). A second important group of substances are interferons. They have antiviral but also immunomodulating activities. The third and most recently discovered group includes biological and cellular therapeutics. Soluble receptor analogues (e.g., sCAR-Fc) bind to the virus capsid and block virus uptake. Small interfering RNAs, short hairpin RNAs and antisense oligonucleotides bind to and led to degradation of the viral RNA genome or cellular RNAs, thereby preventing their translation and viral replication. Most recently mesenchymal stem cell transplantation has been shown to possess antiviral activity in CVB3 infections. Taken together, a number of antiviral therapeutics has been developed for the treatment of myocardial CVB infection in recent years. In addition to low molecular weight inhibitors, biological therapeutics have become promising anti-viral agents.",2011 Oct 11,"['Fechner, Henry', 'Pinkert, Sandra', 'Geisler, Anja', 'Poller, Wolfgang', 'Kurreck, Jens']",Molecules,,,True
f2d842780b9928cc70f38a4458553f2431877603,PMC,Inhibitory Effect and Possible Mechanism of Action of Patchouli Alcohol against Influenza A (H2N2) Virus,http://dx.doi.org/10.3390/molecules16086489,PMC6264369,21814161,CC BY,"In the present study, the anti-influenza A (H2N2) virus activity of patchouli alcohol was studied in vitro, in vivo and in silico. The CC(50) of patchouli alcohol was above 20 µM. Patchouli alcohol could inhibit influenza virus with an IC(50) of 4.03 ± 0.23 µM. MTT assay showed that the inhibition by patchouli alcohol appears strongly after penetration of the virus into the cell. In the influenza mouse model, patchouli alcohol showed obvious protection against the viral infection at a dose of 5 mg/kg/day. Flexible docking and molecular dynamic simulations indicated that patchouli alcohol was bound to the neuraminidase protein of influenza virus, with an interaction energy of –40.38 kcal mol(–1). The invariant key active-site residues Asp151, Arg152, Glu119, Glu276 and Tyr406 played important roles during the binding process. Based on spatial and energetic criteria, patchouli alcohol interfered with the NA functions. Results presented here suggest that patchouli alcohol possesses anti-influenza A (H2N2) virus properties, and therefore is a potential source of anti-influenza agents for the pharmaceutical industry.",2011 Aug 3,"['Wu, Huaxing', 'Li, Beili', 'Wang, Xue', 'Jin, Mingyuan', 'Wang, Guonian']",Molecules,,,True
10206d084e0ca2117abdb7f6909d9b857ec89b69,PMC,A global bibliometric analysis of Plesiomonas-related research (1990 – 2017),http://dx.doi.org/10.1371/journal.pone.0207655,PMC6264487,30496198,CC BY,"Plesiomonas shigelloides is an emerging pathogen with damaging effects on human health such as gastroenteritis and extraintestinal infections. Here, we carried out a bibliometric survey that aimed to examine publication trends in Plesiomonas-related research by time and place, international collaborative works, identify gaps and suggest directions for future research. The search term “Plesiomonas shigelloides” was used to retrieve articles published between 1990 and 2017 from the Web of Science database. Only primary research articles were included in the analysis. A total of 155 articles were published within the survey period, with an average of 5.54±2.66 articles per year and an annual growth rate of −0.8%. Research output peaked in 2000 and 2006 (each accounting for 7.7% of the total). The United States ranked first in terms of numbers of articles (n = 29, 18.1%) and total citations (n = 451). Cameroon, Canada, Cuba, Switzerland and Turkey co-shared the 10(th) position each with 2 articles (1.3%). Research collaboration was low (collaboration index = 3. 32). In addition to Plesiomonas shigelloides (n = 82, 52.9%), the top Authors Keywords and research focus included lipopolysaccharide and nuclear magnetic resonance (n = 13, 8.4%). Diarrhea (n = 43, 27.7%), Aeromonas species (n = 41, 26.5%) and infections (n = 31, 20.0%) were also highly represented in Keywords-Plus. Authors’ collaborations and coupling networks formed two mega-clusters which nodes were shared solely by authors from high-income countries. The common conceptual framework in retrieved articles determined by K-means clustering revealed three clusters with sizes of 7, 16, and 29, representing research responses focused on extraintestinal and gastroenteritis, P. shigelloides lipopolysaccharide structure, and co-infections, respectively. Our bibliometric analysis revealed a global diminishing research in Plesiomonas; greater research outcomes from high-income countries compared to others and low collaboration with developing countries.",2018 Nov 29,"['Ekundayo, Temitope Cyrus', 'Okoh, Anthony I.']",PLoS One,,,True
b2c35edb017ca3e5f0d14a0155034e02851f814a,PMC,Discovery of Potential M2 Channel Inhibitors Based on the Amantadine Scaffold via Virtual Screening and Pharmacophore Modeling,http://dx.doi.org/10.3390/molecules161210227,PMC6264534,22158591,CC BY,"The M2 channel protein on the influenza A virus membrane has become the main target of the anti-flu drugs amantadine and rimantadine. The structure of the M2 channel proteins of the H3N2 (PDB code 2RLF) and 2009-H1N1 (Genbank accession number GQ385383) viruses may help researchers to solve the drug-resistant problem of these two adamantane-based drugs and develop more powerful new drugs against influenza A virus. In the present study, we searched for new M2 channel inhibitors through a combination of different computational methodologies, including virtual screening with docking and pharmacophore modeling. Virtual screening was performed to calculate the free energies of binding between receptor M2 channel proteins and 200 new designed ligands. After that, pharmacophore analysis was used to identify the important M2 protein-inhibitor interactions and common features of top binding compounds with M2 channel proteins. Finally, the two most potential compounds were determined as novel leads to inhibit M2 channel proteins in both H3N2 and 2009-H1N1 influenza A virus.",2011 Dec 8,"['Tran, Linh', 'Choi, Sy Bing', 'Al-Najjar, Belal O.', 'Yusuf, Muhammad', 'Wahab, Habibah A.', 'Le, Ly']",Molecules,,,True
dd46b3a35a8a6299b52a23022b0d5d9c23e24ae0,PMC,Three New Cycloartenol Triterpenoid Saponins from the Roots of Cimicifuga simplex Wormsk,http://dx.doi.org/10.3390/molecules16064348,PMC6264577,21613976,CC BY,"Three new cycloartenol triterpene saponins, named shengmaxinsides A-C, have been isolated from the ethyl acetate soluble fraction of an ethanol extract of Cimicifuga simplex Wormsk roots. Their structures were established by chemical tests and detailed spectroscopic analysis as 25-O-acetyl-7,8-didehydrocimigenol-3-O-β-D-galactopyranoside (1), 7,8-didehydrocimigenol-3-O-β-D-galactopyranoside (2) and 7,8-didehydro-24S-O-acetylhydroshengmanol-3-O-β-D-galactopyranoside (3), respectively.",2011 May 25,"['Kuang, Haixue', 'Su, Yang', 'Yang, Bingyou', 'Xia, Yonggang', 'Wang, Qiuhong', 'Wang, Zhibin', 'Yu, Zhengfan']",Molecules,,,True
fbd7cb291782d73cc8b480cddd13f2b664f25cdb,PMC,Silver Nanoparticles as Potential Antiviral Agents,http://dx.doi.org/10.3390/molecules16108894,PMC6264685,22024958,CC BY,"Virus infections pose significant global health challenges, especially in view of the fact that the emergence of resistant viral strains and the adverse side effects associated with prolonged use continue to slow down the application of effective antiviral therapies. This makes imperative the need for the development of safe and potent alternatives to conventional antiviral drugs. In the present scenario, nanoscale materials have emerged as novel antiviral agents for the possibilities offered by their unique chemical and physical properties. Silver nanoparticles have mainly been studied for their antimicrobial potential against bacteria, but have also proven to be active against several types of viruses including human imunodeficiency virus, hepatitis B virus, herpes simplex virus, respiratory syncytial virus, and monkey pox virus. The use of metal nanoparticles provides an interesting opportunity for novel antiviral therapies. Since metals may attack a broad range of targets in the virus there is a lower possibility to develop resistance as compared to conventional antivirals. The present review focuses on the development of methods for the production of silver nanoparticles and on their use as antiviral therapeutics against pathogenic viruses.",2011 Oct 24,"['Galdiero, Stefania', 'Falanga, Annarita', 'Vitiello, Mariateresa', 'Cantisani, Marco', 'Marra, Veronica', 'Galdiero, Massimiliano']",Molecules,,,True
93db9dda052bb8f92973c8c0ffe4ab8a1364a7ef,PMC,Synthesis and Toxicity Evaluation of Some N(4)-Aryl Substituted 5-Trifluoromethoxyisatin-3-thiosemicarbazones,http://dx.doi.org/10.3390/molecules16086408,PMC6264754,25134761,CC BY,"A series of twenty one N(4)-aryl substituted 5-trifluoromethoxyisatin-3-thiosemicarbazones 3a-3u was synthesized by the reaction of trifluoromethoxyisatin 1 with different arylthiosemicarbazides 2 in aqueous ethanol (50%), containing a few drops of acetic acid. Their structures were established on the basis of analytical (CHN) and spectral (IR, (1)H-NMR, EIMS) data. All the synthesized compounds were evaluated for their toxicity potential by a brine shrimp lethality bioassay. Ten compounds i.e., 3a, 3e, 3i-3l and 3n-3q proved to be active in this assay, displaying promising toxicity (LD(50) = 1.11 × 10(−5) M − 1.80 × 10(−4) M). Amongst these, 3k, 3n and 3o were found to be the most active ones (LD(50) = 1.11 × 10(−5) M − 1.43 × 10(−5) M). Compound 3k showed the highest activity with a LD(50) value of 1.11 × 10(−5) M and can, therefore, be used as a lead for further studies. Structure-activity relationship (SAR) studies revealed that the presence of strong inductively electron-attracting trifluoromethoxy substituent at position-5 of the isatin moiety played an important role in inducing or enhancing toxic potentiality of some of the synthesized compounds.",2011 Jul 29,"['Pervez, Humayun', 'Saira, Naveeda', 'Iqbal, Mohammad Saeed', 'Yaqub, Muhammad', 'Khan, Khalid Mohammed']",Molecules,,,True
5b9c63d5acc2fe8fde000803aca5a7e6a0d6df75,PMC,"Benzylidene-bis-(4-Hydroxycoumarin) and Benzopyrano-Coumarin Derivatives: Synthesis, (1)H/(13)C-NMR Conformational and X-ray Crystal Structure Studies and In Vitro Antiviral Activity Evaluations",http://dx.doi.org/10.3390/molecules16076023,PMC6264767,21772234,CC BY,"We report on the synthesis of 4-hydroxycoumarin dimers 1–15 bearing an aryl substituent on the central linker and fused benzopyranocoumarin derivatives 16–20 and on their in vitro broad anti-DNA and RNA virus activity evaluations. The chemical identities and structure of compounds 1–20 were deduced from their homo- and heteronuclear NMR measurements whereas the conformational properties of 5, 14 and 20 were assessed by the use of 1D difference NOE enhancements. Unequivocal proof of the stereostructure of compounds 7, 9, 16 and 18 was obtained by single crystal X-ray diffraction method. The X-ray crystal structure analysis revealed that two 4-hydroxycoumarin moieties in the 4-trifluoromethylphenyl- and 2-nitrophenyl derivatives (compounds 7 and 9, respectively) are intramolecularly hydrogen-bonded between hydroxyl and carbonyl oxygen atoms. Consequently, the compounds 7 and 9 adopt conformations in which two 4-hydroxy-coumarin moieties are anti-disposed. Antiviral activity evaluation results indicated that the 4-bromobenzylidene derivative of bis-(4-hydroxycoumarin) (compound 3) possesses inhibitory activity against HSV-1 (KOS), HSV-2 (G), vaccinia virus and HSV-1 TK(-) KOS (ACV(r)) at a concentration of 9–12 μM and at a minimum cytotoxic concentration (MCC) greater than 20 μM. Compounds 4–6, 8, and 20 were active against feline herpes virus (50% effective concentration, EC(50) = 5–8.1 μM), that is at a 4-7-fold lower concentration than the MCC.",2011 Jul 19,"['Završnik, Davorka', 'Muratović, Samija', 'Makuc, Damjan', 'Plavec, Janez', 'Cetina, Mario', 'Nagl, Ante', 'De Clercq, Erik', 'Balzarini, Jan', 'Mintas, Mladen']",Molecules,,,True
68b617740b5abe48673b58026457150cf7fc5985,PMC,Integrated Disease Surveillance and Response (IDSR) in Malawi: Implementation gaps and challenges for timely alert,http://dx.doi.org/10.1371/journal.pone.0200858,PMC6264833,30496177,CC BY,"OBJECTIVE: The recent 2014 Ebola Virus Disease (EVD) outbreaks rang the bell to call upon global efforts to assist resource-constrained countries to strengthen public health surveillance system for early response. Malawi adopted the Integrated Disease Surveillance and Response (IDSR) strategy to develop its national surveillance system since 2002 and revised its guideline to fulfill the International Health Regulation (IHR) requirements in 2014. This study aimed to understand the state of IDSR implementation and differences between guideline and practice for future disease surveillance system strengthening. METHODS: This was a mixed-method research study. Quantitative data were to analyze completeness and timeliness of surveillance system performance from national District Health Information System 2 (DHIS2) during October 2014 to September 2016. Qualitative data were collected through interviews with 29 frontline health service providers from the selected district and 7 key informants of the IDSR system implementation and administration at district and national levels. FINDINGS: The current IDSR system showed relatively good completeness (73.1%) but poor timeliness (40.2%) of total expected monthly reports nationwide and zero weekly reports during the study period. Major implementation gaps were lack of weekly report and trainings. The challenges of IDSR implementation revealed through qualitative data included case identification, compiling reports for timely submission and inadequate resources. CONCLUSIONS: The differences between IDSR technical guideline and actual practice were huge. The developing information technology infrastructure in Malawi and emerging mobile health (mHealth) technology can be opportunities for the country to overcome these challenges and improve surveillance system to have better timeliness for the outbreaks and unusual events detection.",2018 Nov 29,"['Joseph Wu, Tsung-Shu', 'Kagoli, Matthew', 'Kaasbøll, Jens Johan', 'Bjune, Gunnar Aksel']",PLoS One,,,True
468d8047a0283ba355246ed938fac8434a589a26,PMC,Structural and mechanistic basis for preferential deadenylation of U6 snRNA by Usb1,http://dx.doi.org/10.1093/nar/gky812,PMC6265477,30215753,CC BY,"Post-transcriptional modification of snRNA is central to spliceosome function. Usb1 is an exoribonuclease that shortens the oligo-uridine tail of U6 snRNA, resulting in a terminal 2′,3′ cyclic phosphate group in most eukaryotes, including humans. Loss of function mutations in human Usb1 cause the rare disorder poikiloderma with neutropenia (PN), and result in U6 snRNAs with elongated 3′ ends that are aberrantly adenylated. Here, we show that human Usb1 removes 3′ adenosines with 20-fold greater efficiency than uridines, which explains the presence of adenylated U6 snRNAs in cells lacking Usb1. We determined three high-resolution co-crystal structures of Usb1: wild-type Usb1 bound to the substrate analog adenosine 5′-monophosphate, and an inactive mutant bound to RNAs with a 3′ terminal adenosine and uridine. These structures, along with QM/MM MD simulations of the catalytic mechanism, illuminate the molecular basis for preferential deadenylation of U6 snRNA. The extent of Usb1 processing is influenced by the secondary structure of U6 snRNA.",2018 Nov 30,"['Nomura, Yuichiro', 'Roston, Daniel', 'Montemayor, Eric J', 'Cui, Qiang', 'Butcher, Samuel E']",Nucleic Acids Res,,,True
2a3e6aaf35057f4222ef436b616e9d05106e076e,PMC,Immunogenicity of Pigeon Circovirus Recombinant Capsid Protein in Pigeons,http://dx.doi.org/10.3390/v10110596,PMC6265742,30384424,CC BY,"Pigeon circovirus (PiCV) is the most frequently diagnosed virus in pigeons and is thought to be one of the causative factors of a complex disease called the young pigeon disease syndrome (YPDS). The development of a vaccine against this virus could be a strategy for YPDS control. Since laboratory culture of PiCV is impossible, its recombinant capsid protein (rCP) can be considered as a potential antigen candidate in sub-unit vaccines. The aim of this basic research was to evaluate the immune response of pigeons to PiCV rCP. Sixty six-week-old carrier pigeons were divided into two groups (experimental immunized with PiCV rCP mixed with an adjuvant, and control immunized with an adjuvant only), and immunized twice in a 21-day interval. On the day of immunization and on two, 23, 39, and 46 days post first immunization (dpv), samples of blood, spleen, and bursa of Fabricius were collected from six birds from each group to examine anti-PiCV rCP IgY, anti-PiCV rCP IgY-secreting B cells (SBC), IFN-γ gene expression, and percentage of T CD3(+), CD4(+), CD8(+), and B IgM(+) lymphocytes. The results indicated a correct immune response to PiCV rCP both in humoral and cell-mediated immunity, which was manifested by seroconversion since 23 dpv, by a significantly higher anti-PiCV rCP IgY-SBC number on two and 23 dpv, and significantly higher IFN-γ gene expression since two dpv. There were no significant differences or trends noted between particular T and B lymphocyte subpopulations. To conclude, PiCV rCP may be deemed immunogenic and could be considered as an antigen candidate in sub-unit vaccines against PiCV infections in pigeons.",2018 Oct 31,"['Stenzel, Tomasz', 'Dziewulska, Daria', 'Tykałowski, Bartłomiej', 'Śmiałek, Marcin', 'Kowalczyk, Joanna', 'Koncicki, Andrzej']",Viruses,,,True
5408b9cea3b1caf9f6cd026140d5414fab4c6e81,PMC,Agent-Based Modeling for Super-Spreading Events: A Case Study of MERS-CoV Transmission Dynamics in the Republic of Korea,http://dx.doi.org/10.3390/ijerph15112369,PMC6265857,30373151,CC BY,"Super-spreading events have been observed in the transmission dynamics of many infectious diseases. The 2015 MERS-CoV outbreak in the Republic of Korea has also shown super-spreading events with a significantly high level of heterogeneity in generating secondary cases. It becomes critical to understand the mechanism for this high level of heterogeneity to develop effective intervention strategies and preventive plans for future emerging infectious diseases. In this regard, agent-based modeling is a useful tool for incorporating individual heterogeneity into the epidemic model. In the present work, a stochastic agent-based framework is developed in order to understand the underlying mechanism of heterogeneity. Clinical (i.e., an infectivity level) and social or environmental (i.e., a contact level) heterogeneity are modeled. These factors are incorporated in the transmission rate functions under assumptions that super-spreaders have stronger transmission and/or higher links. Our agent-based model has employed real MERS-CoV epidemic features based on the 2015 MERS-CoV epidemiological data. Monte Carlo simulations are carried out under various epidemic scenarios. Our findings highlight the roles of super-spreaders in a high level of heterogeneity, underscoring that the number of contacts combined with a higher level of infectivity are the most critical factors for substantial heterogeneity in generating secondary cases of the 2015 MERS-CoV transmission.",2018 Nov 26,"['Kim, Yunhwan', 'Ryu, Hohyung', 'Lee, Sunmi']",Int J Environ Res Public Health,,,True
94cad8eb2f7ef7b18edd43115de077da98425871,PMC,"ISG15, a Small Molecule with Huge Implications: Regulation of Mitochondrial Homeostasis",http://dx.doi.org/10.3390/v10110629,PMC6265978,30428561,CC BY,"Viruses are responsible for the majority of infectious diseases, from the common cold to HIV/AIDS or hemorrhagic fevers, the latter with devastating effects on the human population. Accordingly, the development of efficient antiviral therapies is a major goal and a challenge for the scientific community, as we are still far from understanding the molecular mechanisms that operate after virus infection. Interferon-stimulated gene 15 (ISG15) plays an important antiviral role during viral infection. ISG15 catalyzes a ubiquitin-like post-translational modification termed ISGylation, involving the conjugation of ISG15 molecules to de novo synthesized viral or cellular proteins, which regulates their stability and function. Numerous biomedically relevant viruses are targets of ISG15, as well as proteins involved in antiviral immunity. Beyond their role as cellular powerhouses, mitochondria are multifunctional organelles that act as signaling hubs in antiviral responses. In this review, we give an overview of the biological consequences of ISGylation for virus infection and host defense. We also compare several published proteomic studies to identify and classify potential mitochondrial ISGylation targets. Finally, based on our recent observations, we discuss the essential functions of mitochondria in the antiviral response and examine the role of ISG15 in the regulation of mitochondrial processes, specifically OXPHOS and mitophagy.",2018 Nov 13,"['Albert, Manuel', 'Bécares, Martina', 'Falqui, Michela', 'Fernández-Lozano, Carlos', 'Guerra, Susana']",Viruses,,,True
e9d01ab9a55093ad1c1277a7845d3254d3ad6fe8,PMC,"Cystic Fibrosis Gene Therapy: Looking Back, Looking Forward",http://dx.doi.org/10.3390/genes9110538,PMC6266271,30405068,CC BY,"Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes a cAMP-regulated anion channel. Although CF is a multi-organ system disease, most people with CF die of progressive lung disease that begins early in childhood and is characterized by chronic bacterial infection and inflammation. Nearly 90% of people with CF have at least one copy of the ΔF508 mutation, but there are hundreds of CFTR mutations that result in a range of disease severities. A CFTR gene replacement approach would be efficacious regardless of the disease-causing mutation. After the discovery of the CFTR gene in 1989, the in vitro proof-of-concept for gene therapy for CF was quickly established in 1990. In 1993, the first of many gene therapy clinical trials attempted to rescue the CF defect in airway epithelia. Despite the initial enthusiasm, there is still no FDA-approved gene therapy for CF. Here we discuss the history of CF gene therapy, from the discovery of the CFTR gene to current state-of-the-art gene delivery vector designs. While implementation of CF gene therapy has proven more challenging than initially envisioned; thanks to continued innovation, it may yet become a reality.",2018 Nov 7,"['Cooney, Ashley L.', 'McCray, Paul B.', 'Sinn, Patrick L.']",Genes (Basel),,,True
7cdd0a62e95aebd067147c0fd81ec62dce46ad42,PMC,The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo,http://dx.doi.org/10.3390/v10110601,PMC6266276,30388805,CC BY,"To complement traditional antivirals, natural compounds that act via host targets and present high barriers to resistance are of increasing interest. In the work reported here, we detected that homoharringtonine (HHT) presents effective antiviral activity. HHT completely inhibited infections of vesicular stomatitis virus (VSV), Newcastle disease virus (NDV), and porcine epidemic diarrhea virus (PEDV) at concentrations of 50, 100, and 500 nM in cell cultures, respectively. Treatment with HHT at doses of 0.05 or 0.2 mg/kg significantly reduced viral load and relieved severe symptoms in PEDV- or NDV-infected animals. HHT treatment, however, moderately inhibited avian influenza virus (AIV) infection, suggesting its potent antiviral action is restricted to a number of classes of RNA viruses. In this study, we also observed that HHT actively inhibited herpes simplex virus type 1 (HSV-1) replication with a 50% inhibitory concentration (IC(50)) of 139 nM; the treatment with HHT at 1000 nM led to reductions of three orders of magnitude. Moreover, HHT antagonized the phosphorylation level of endogenous and exogenous eukaryotic initiation factor 4E (p-eIF4E), which might regulate the selective translation of specific messenger RNA (mRNA). HHT provides a starting point for further progress toward the clinical development of broad-spectrum antivirals.",2018 Nov 1,"['Dong, Hui-Jun', 'Wang, Zhao-Hua', 'Meng, Wen', 'Li, Cui-Cui', 'Hu, Yan-Xin', 'Zhou, Lei', 'Wang, Xiao-Jia']",Viruses,,,True
66a3eded4d7bae681a0079a333c4acb75fe05828,PMC,"Human bocavirus, coronavirus, and polyomavirus detected among patients hospitalised with severe acute respiratory illness in South Africa, 2012 to 2013",http://dx.doi.org/10.1002/hsr2.59,PMC6266378,30623094,CC BY,"AIM: To investigate the prevalence of human bocavirus (hBoV), human coronaviruses (hCoV), and human polyomaviruses (hPyV) among patients with severe acute respiratory illness (SARI), in South Africa. METHODS: The study included 680 South African patients randomly selected in age‐defined categories from hospitalised patients enrolled through SARI surveillance during 2012 to 2013. A multiplex reverse transcription real‐time polymerase chain reaction assay was used to detect hBoV; hCoV‐OC43, hCoV‐229E, hCoV‐NL63, and hCoV‐HKU1; and Washington University hPyV (hPyV‐WU) and Karolinska Insitute hPyV (hPyV‐KI), in respiratory tract specimens collected from patients with SARI. All respiratory specimens from patients enrolled through SARI surveillance were also routinely tested by multiplex reverse transcription real‐time polymerase chain reaction for adenovirus; enterovirus; human metapneumovirus; parainfluenza virus types 1, 2, and 3; respiratory syncytial virus; rhinovirus; influenza A, and influenza B. RESULTS: Human bocavirus, hCoV‐229E, and hPyV‐WU were detected in 3.7% (25/680), 4.1% (28/680), and 4.1% (28/680) of respiratory specimens, respectively. All other viruses were detected in <2% of specimens. Rhinovirus was the most common coinfecting virus (21.4%‐60.7%), followed by adenovirus (21.4%‐39.3%), and respiratory syncytial virus (10.7%‐24.0%). Testing for the additional viruses (hBoV, hCoV, and hPyV) decreased the number of specimens that initially tested negative by 2.9% (20/680). CONCLUSION: Inclusion of laboratory tests for hBoV, hCoV‐229E, and hPyV‐WU in differential testing algorithms for surveillance and diagnostics for suspected cases of respiratory illness of unknown cause may improve our understanding of the etiology of SARI, especially in a country like South Africa with a high number of immune compromised persons.",2018 Jul 18,"['Subramoney, Kathleen', 'Hellferscee, Orienka', 'Pretorius, Marthi', 'Tempia, Stefano', 'McMorrow, Meredith', 'von Gottberg, Anne', 'Wolter, Nicole', 'Variava, Ebrahim', 'Dawood, Halima', 'Kahn, Kathleen', 'Walaza, Sibongile', 'Madhi, Shabir A.', 'Cohen, Cheryl', 'Venter, Marietjie', 'Treurnicht, Florette K.']",Health Sci Rep,,,True
df82c611eb38c4c9dbef1a86da01ca432e61c8f7,PMC,Pathobiological and Genomic Characterization of a Cold-Adapted Infectious Bronchitis Virus (BP-caKII),http://dx.doi.org/10.3390/v10110652,PMC6266813,30463206,CC BY,"We established a cold-adapted infectious bronchitis virus (BP-caKII) by passaging a field virus through specific pathogen-free embryonated eggs 20 times at 32 °C. We characterized its growth kinetics and pathogenicity in embryonated eggs, and its tropism and persistence in different tissues from chickens; then, we evaluated pathogenicity by using a new premature reproductive tract pathogenicity model. Furthermore, we determined the complete genomic sequence of BP-caKII to understand the genetic changes related to cold adaptation. According to our results, BP-caKII clustered with the KII genotype viruses K2 and KM91, and showed less pathogenicity than K2, a live attenuated vaccine strain. BP-caKII showed delayed viremia, resulting in its delayed dissemination to the kidneys and cecal tonsils compared to K2 and KM91, the latter of which is a pathogenic field strain. A comparative genomics study revealed similar nucleotide sequences between BP-caKII, K2 and KM91 but clearly showed different mutations among them. BP-caKII shared several mutations with K2 (nsp13, 14, 15 and 16) following embryo adaptation but acquired multiple additional mutations in nonstructural proteins (nsp3, 4 and 12), spike proteins and nucleocapsid proteins following cold adaptation. Thus, the establishment of BP-caKII and the identified mutations in this study may provide insight into the genetic background of embryo and cold adaptations, and the attenuation of coronaviruses.",2018 Nov 19,"['Hong, Seung-Min', 'An, Se-Hee', 'Lee, Chung-Young', 'Song, Chang-Seon', 'Choi, Kang-Seuk', 'Kim, Jae-Hong', 'Kwon, Hyuk-Joon']",Viruses,,,True
6ed847ce64787a0058d12bce4edc3eb43d837076,PMC,Pathobiological and Genomic Characterization of a Cold-Adapted Infectious Bronchitis Virus (BP-caKII),http://dx.doi.org/10.3390/v10110652,PMC6266813,30463206,CC BY,"We established a cold-adapted infectious bronchitis virus (BP-caKII) by passaging a field virus through specific pathogen-free embryonated eggs 20 times at 32 °C. We characterized its growth kinetics and pathogenicity in embryonated eggs, and its tropism and persistence in different tissues from chickens; then, we evaluated pathogenicity by using a new premature reproductive tract pathogenicity model. Furthermore, we determined the complete genomic sequence of BP-caKII to understand the genetic changes related to cold adaptation. According to our results, BP-caKII clustered with the KII genotype viruses K2 and KM91, and showed less pathogenicity than K2, a live attenuated vaccine strain. BP-caKII showed delayed viremia, resulting in its delayed dissemination to the kidneys and cecal tonsils compared to K2 and KM91, the latter of which is a pathogenic field strain. A comparative genomics study revealed similar nucleotide sequences between BP-caKII, K2 and KM91 but clearly showed different mutations among them. BP-caKII shared several mutations with K2 (nsp13, 14, 15 and 16) following embryo adaptation but acquired multiple additional mutations in nonstructural proteins (nsp3, 4 and 12), spike proteins and nucleocapsid proteins following cold adaptation. Thus, the establishment of BP-caKII and the identified mutations in this study may provide insight into the genetic background of embryo and cold adaptations, and the attenuation of coronaviruses.",2018 Nov 19,"['Hong, Seung-Min', 'An, Se-Hee', 'Lee, Chung-Young', 'Song, Chang-Seon', 'Choi, Kang-Seuk', 'Kim, Jae-Hong', 'Kwon, Hyuk-Joon']",Viruses,,,False
d31b3d462fe4af4bac27a166ddfdf39b03c8e911,PMC,Reverse Genetic Approaches for the Generation of Recombinant Zika Virus,http://dx.doi.org/10.3390/v10110597,PMC6266887,30384426,CC BY,"Zika virus (ZIKV) is an emergent mosquito-borne member of the Flaviviridae family that was responsible for a recent epidemic in the Americas. ZIKV has been associated with severe clinical complications, including neurological disorder such as Guillain-Barré syndrome in adults and severe fetal abnormalities and microcephaly in newborn infants. Given the significance of these clinical manifestations, the development of tools and reagents to study the pathogenesis of ZIKV and to develop new therapeutic options are urgently needed. In this respect, the implementation of reverse genetic techniques has allowed the direct manipulation of the viral genome to generate recombinant (r)ZIKVs, which have provided investigators with powerful systems to answer important questions about the biology of ZIKV, including virus-host interactions, the mechanism of transmission and pathogenesis or the function of viral proteins. In this review, we will summarize the different reverse genetic strategies that have been implemented, to date, for the generation of rZIKVs and the applications of these platforms for the development of replicon systems or reporter-expressing viruses.",2018 Oct 31,"['Ávila-Pérez, Ginés', 'Nogales, Aitor', 'Martín, Verónica', 'Almazán, Fernando', 'Martínez-Sobrido, Luis']",Viruses,,,True
4faaf584315206f342db3f18a118eae7ca702146,PMC,The In Ovo Delivery of CpG Oligonucleotides Protects against Infectious Bronchitis with the Recruitment of Immune Cells into the Respiratory Tract of Chickens,http://dx.doi.org/10.3390/v10110635,PMC6266937,30445707,CC BY,"The in ovo delivery of cytosine-guanosine (CpG) oligodeoxynucleotides (ODNs) protects chickens against many bacterial and viral infections, by activating the toll-like receptor (TLR)21 signaling pathway. Although the delivery of CpG ODNs in ovo at embryo day (ED) 18 has been shown to reduce infectious bronchitis virus (IBV) loads in embryonic chicken lungs pre-hatch, whether in ovo delivered CpG ODNs are capable of protecting chickens against a post-hatch challenge is unknown. Thus, our objectives were to determine the protective effect of the in ovo delivery of CpG ODNs at ED 18 against IBV infection encountered post-hatch and, then, to investigate the mechanisms of protection. We found significantly higher survival rates and reduced IBV infection in the chickens following the pre-treatment of the ED 18 eggs with CpG ODNs. At 3 days post infection (dpi), we found an increased recruitment of macrophages, cluster of differentiation (CD)8α+ and CD4+ T lymphocytes, and an up-regulation of interferon (IFN)-γ mRNA in the respiratory tract of the chickens. Overall, it may be inferred that CpG ODNs, when delivered in ovo, provide protection against IBV infection induced morbidity and mortality with an enhanced immune response.",2018 Nov 15,"['De Silva Senapathi, Upasama', 'Abdul-Cader, Mohamed Sarjoon', 'Amarasinghe, Aruna', 'van Marle, Guido', 'Czub, Markus', 'Gomis, Susantha', 'Abdul-Careem, Mohamed Faizal']",Viruses,,,True
728443b747cf0b0f8e2ef586044140357b2a59c5,PMC,The In Ovo Delivery of CpG Oligonucleotides Protects against Infectious Bronchitis with the Recruitment of Immune Cells into the Respiratory Tract of Chickens,http://dx.doi.org/10.3390/v10110635,PMC6266937,30445707,CC BY,"The in ovo delivery of cytosine-guanosine (CpG) oligodeoxynucleotides (ODNs) protects chickens against many bacterial and viral infections, by activating the toll-like receptor (TLR)21 signaling pathway. Although the delivery of CpG ODNs in ovo at embryo day (ED) 18 has been shown to reduce infectious bronchitis virus (IBV) loads in embryonic chicken lungs pre-hatch, whether in ovo delivered CpG ODNs are capable of protecting chickens against a post-hatch challenge is unknown. Thus, our objectives were to determine the protective effect of the in ovo delivery of CpG ODNs at ED 18 against IBV infection encountered post-hatch and, then, to investigate the mechanisms of protection. We found significantly higher survival rates and reduced IBV infection in the chickens following the pre-treatment of the ED 18 eggs with CpG ODNs. At 3 days post infection (dpi), we found an increased recruitment of macrophages, cluster of differentiation (CD)8α+ and CD4+ T lymphocytes, and an up-regulation of interferon (IFN)-γ mRNA in the respiratory tract of the chickens. Overall, it may be inferred that CpG ODNs, when delivered in ovo, provide protection against IBV infection induced morbidity and mortality with an enhanced immune response.",2018 Nov 15,"['De Silva Senapathi, Upasama', 'Abdul-Cader, Mohamed Sarjoon', 'Amarasinghe, Aruna', 'van Marle, Guido', 'Czub, Markus', 'Gomis, Susantha', 'Abdul-Careem, Mohamed Faizal']",Viruses,,,False
30c57af407724c03de7e5b24b175c3de44ea79a6,PMC,Utilization of Chinese medicine for respiratory discomforts by patients with a medical history of tuberculosis in Taiwan,http://dx.doi.org/10.1186/s12906-018-2377-4,PMC6267063,30497462,CC BY,"BACKGROUND: Tuberculosis (TB) is one of the world’s major communicable infectious diseases, and it still imposes a great health burden in developing countries. The development of drug-resistant TB during the treatment increases the treatment complexity, and the long-term pulmonary complications after completing treatment raise the epidemic health burden. This study intended to investigate the utilization of Chinese medicine (CM) for respiratory symptoms by patients with a medical history of TB in Taiwan. METHODS: We analyzed a cohort of one million individuals who were randomly selected from the National Health Insurance Research Database in Taiwan. The inclusion criteria of patients (n = 7905) with history of TB (ICD-9-CM codes 010–018 and A02) were: (1) TB diagnosed between January 1, 1997 and December 31, 2010 (2) 18 years old or over (3) Clinical records for at least 2 months with complete demographic information (4) Record of treatment with first-line TB medication prescriptions. CM users for conditions other than respiratory discomforts (n = 3980) were excluded. Finally, a total of 3925 TB patients were categorized as: CM users for respiratory discomforts (n = 2051) and non-CM users (n = 1874). RESULTS: Among the 3925 subjects, 2051 (52.25%) were CM users, and 1874 (44.753%) were non-CM users. Female patients and those who were younger (18–39 y/o) and who lived in urbanized areas relatively tended to be CM users (p < .0001). Most of the CM users (1944, 94.78%) received Chinese medicines. The most commonly prescribed herbal formulas and single herbs were Xiao-Qing-Long-Tang and Radix Platycodonis (Jie-Geng), respectively. The core pattern of Chinese medicines for TB patients consisted of Ma-Xing-Gan-Shi-Tang, Bulbus Fritillariae Thunbergii (Bei-Mu), Radix Platycodonis (Jie-Geng) and Semen Armeniacae (Xing-Ren). CONCLUSIONS: The use of CM is popular among patients with a medical history of TB complicated with long-term respiratory discomforts in Taiwan. Further pharmacological investigations and clinical trials are required.",2018 Nov 29,"['Yang, Su-Tso', 'Lin, Yi-Rong', 'Wu, Mei-Yao', 'Chiang, Jen-Huai', 'Yang, Pei-Shan', 'Hsia, Te-Chun', 'Yen, Hung-Rong']",BMC Complement Altern Med,,,True
5c5491d07d2c4e996988e591b870ed272d2f944e,PMC,2′-5′-Oligoadenylate synthetase 1 polymorphisms are associated with tuberculosis: a case-control study,http://dx.doi.org/10.1186/s12890-018-0746-x,PMC6267069,30497421,CC BY,"BACKGROUND: 2′-5′-Oligoadenylate synthetase 1 (OAS1) plays an important role in inflammatory immune reactions. OAS1 polymorphisms have been associated with increased susceptibility to various diseases. We investigated the association of polymorphisms in OAS1 with tuberculosis (TB). METHODS: A total of 1215 TB cases and 1114 healthy controls were enrolled from two independent studies. Genotyping was conducted using the improved multiplex ligase detection reaction (iMLDR) method. Associations between OAS1 polymorphisms (rs2240190, rs1131454, 10,774,671 and 11,066,453) and TB risk were established based on distributions of allelic frequencies using different genetic models. RESULTS: Significant association was observed between rs10774671, rs1131454 and TB. In the initial study, the G allele of rs10774671 was a significantly protective factor against TB (P = 0.006) and the genotype of GG differed significantly between TB patients and controls under the codominant model (P = 0.008) after Bonferroni correction. In the validation study, we also observed that the rs10774671 G allele (P = 0.001) and GG genotype (P = 0.001) were associated with TB. In addition, we found that the rs1131454 G allele (P = 0.004) and GG genotype (P = 0.001) were protective against TB in the Chinese Han population. CONCLUSIONS: We report novel associations of polymorphisms in OAS1 with TB in the Chinese Tibetan and Han populations. Similar studies in different populations and functional studies are warranted to confirm our results.",2018 Nov 29,"['Wu, Shouquan', 'Wang, Yu', 'Chen, Guo', 'Zhang, Miaomiao', 'Wang, Minggui', 'He, Jian-Qing']",BMC Pulm Med,,,True
7e884f1a409543ae791d8c5926e126ddcaf2d9b3,PMC,Extracorporeal membrane oxygenation with prone position ventilation successfully rescues infantile pertussis: a case report and literature review,http://dx.doi.org/10.1186/s12887-018-1351-0,PMC6267074,30501615,CC BY,"BACKGROUND: Bordetella pertussis can cause fatal illness with severe acute respiratory distress syndrome (ARDS) and pulmonary hypertension (PHT). CASE PRESENTATION: A 6-month-old non-vaccinated boy with B. pertussis infection who developed ARDS was treated by extracorporeal membrane oxygenation (ECMO). During his ECMO support stage, sudden occurred decreasing of ECMO flow implied increasing intrathoracic pressure. The airway spasm followed caused sudden drop of ventilator tidal volume as well as poor lung compliance. Prone position ventilation and bundle care were conducted as lung protection ventilator strategy. After 297-h of ECMO support, the patient was weaned off ECMO, and extubated one week later. CONCLUSIONS: In this patient with severe ARDS caused by Bordetella pertussis, ECMO was performed for cardiopulmonary support and rescued the infant with severe pertussis. During ECMO support period, prone position ventilation and care bundle nursing strategy contributed to the relief of continuous airway spasm. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12887-018-1351-0) contains supplementary material, which is available to authorized users.",2018 Nov 30,"['Shi, Jingyi', 'Wang, Chunxia', 'Cui, Yun', 'Zhang, Yucai']",BMC Pediatr,,,True
a636cda3a52177d0c79927f54079b476b04b85b3,PMC,RNA Virus Fidelity Mutants: A Useful Tool for Evolutionary Biology or a Complex Challenge?,http://dx.doi.org/10.3390/v10110600,PMC6267201,30388745,CC BY,"RNA viruses replicate with low fidelity due to the error-prone nature of the RNA-dependent RNA polymerase, which generates approximately one mutation per round of genome replication. Due to the large population sizes produced by RNA viruses during replication, this results in a cloud of closely related virus variants during host infection, of which small increases or decreases in replication fidelity have been shown to result in virus attenuation in vivo, but not typically in vitro. Since the discovery of the first RNA virus fidelity mutants during the mid-aughts, the field has exploded with the identification of over 50 virus fidelity mutants distributed amongst 7 RNA virus families. This review summarizes the current RNA virus fidelity mutant literature, with a focus upon the definition of a fidelity mutant as well as methods to confirm any mutational changes associated with the fidelity mutant. Due to the complexity of such a definition, in addition to reports of unstable virus fidelity phenotypes, the future translational utility of these mutants and applications for basic science are examined.",2018 Nov 1,"['Kautz, Tiffany F.', 'Forrester, Naomi L.']",Viruses,,,True
d729eef3818cc854484ab0550aa245e5eaa2b72e,PMC,Association of Candidate Genes with Response to Heat and Newcastle Disease Virus,http://dx.doi.org/10.3390/genes9110560,PMC6267452,30463235,CC BY,"Newcastle disease is considered the number one disease constraint to poultry production in low and middle-income countries, however poultry that is raised in resource-poor areas often experience multiple environmental challenges. Heat stress has a negative impact on production, and immune response to pathogens can be negatively modulated by heat stress. Candidate genes and regions chosen for this study were based on previously reported associations with response to immune stimulants, pathogens, or heat, including: TLR3, TLR7, MX, MHC-B (major histocompatibility complex, gene complex), IFI27L2, SLC5A1, HSPB1, HSPA2, HSPA8, IFRD1, IL18R1, IL1R1, AP2A2, and TOLLIP. Chickens of a commercial egg-laying line were infected with a lentogenic strain of NDV (Newcastle disease virus); half the birds were maintained at thermoneutral temperature and the other half were exposed to high ambient temperature before the NDV challenge and throughout the remainder of the study. Phenotypic responses to heat, to NDV, or to heat + NDV were measured. Selected SNPs (single nucleotide polymorphisms) within 14 target genes or regions were genotyped; and genotype effects on phenotypic responses to NDV or heat + NDV were tested in each individual treatment group and the combined groups. Seventeen significant haplotype effects, among seven genes and seven phenotypes, were detected for response to NDV or heat or NDV + heat. These findings identify specific genetic variants that are associated with response to heat and/or NDV which may be useful in the genetic improvement of chickens to perform favorably when faced with pathogens and heat stress.",2018 Nov 19,"['Rowland, Kaylee', 'Saelao, Perot', 'Wang, Ying', 'Fulton, Janet E.', 'Liebe, Grant N.', 'McCarron, Amy M.', 'Wolc, Anna', 'Gallardo, Rodrigo A.', 'Kelly, Terra', 'Zhou, Huaijun', 'Dekkers, Jack C. M.', 'Lamont, Susan J.']",Genes (Basel),,,True
463e70b355d7cf10d6870a5e14881e0a020ade25,PMC,Association of Candidate Genes with Response to Heat and Newcastle Disease Virus,http://dx.doi.org/10.3390/genes9110560,PMC6267452,30463235,CC BY,"Newcastle disease is considered the number one disease constraint to poultry production in low and middle-income countries, however poultry that is raised in resource-poor areas often experience multiple environmental challenges. Heat stress has a negative impact on production, and immune response to pathogens can be negatively modulated by heat stress. Candidate genes and regions chosen for this study were based on previously reported associations with response to immune stimulants, pathogens, or heat, including: TLR3, TLR7, MX, MHC-B (major histocompatibility complex, gene complex), IFI27L2, SLC5A1, HSPB1, HSPA2, HSPA8, IFRD1, IL18R1, IL1R1, AP2A2, and TOLLIP. Chickens of a commercial egg-laying line were infected with a lentogenic strain of NDV (Newcastle disease virus); half the birds were maintained at thermoneutral temperature and the other half were exposed to high ambient temperature before the NDV challenge and throughout the remainder of the study. Phenotypic responses to heat, to NDV, or to heat + NDV were measured. Selected SNPs (single nucleotide polymorphisms) within 14 target genes or regions were genotyped; and genotype effects on phenotypic responses to NDV or heat + NDV were tested in each individual treatment group and the combined groups. Seventeen significant haplotype effects, among seven genes and seven phenotypes, were detected for response to NDV or heat or NDV + heat. These findings identify specific genetic variants that are associated with response to heat and/or NDV which may be useful in the genetic improvement of chickens to perform favorably when faced with pathogens and heat stress.",2018 Nov 19,"['Rowland, Kaylee', 'Saelao, Perot', 'Wang, Ying', 'Fulton, Janet E.', 'Liebe, Grant N.', 'McCarron, Amy M.', 'Wolc, Anna', 'Gallardo, Rodrigo A.', 'Kelly, Terra', 'Zhou, Huaijun', 'Dekkers, Jack C. M.', 'Lamont, Susan J.']",Genes (Basel),,,False
42a8d5fd943cd29a518ec9683f549f105aac92f8,PMC,"Prevalence of dental caries and associated factors among primary school children: a population-based cross-sectional study in Riyadh, Saudi Arabia",http://dx.doi.org/10.1186/s12199-018-0750-z,PMC6267843,30497366,CC BY,"BACKGROUND: Dental caries is a preventable childhood disease, but public health efforts are hampered due to limited information on associated factors in vulnerable populations. Our study was aimed at estimating the prevalence of dental caries and identifying key associated factors in four major risk domains, including socioeconomic factors, child oral health behavior and practices, child feeding practices, and dietary habits among primary school children in Saudi Arabia. METHODS: A cross-sectional study design was used to recruit 578 male Saudi primary school children, aged 6–8 years, from 12 primary schools in five different regions of Riyadh. Children were clinically screened to detect carious lesions in primary teeth according to World Health Organization’s criteria. Structured self-administered questionnaire was used to collect information on social and individual factors from the parents. The odds ratios and 95% confidence intervals of associated factors for dental caries were computed using logistic regression models; key factors were identified by systematic selection process that accounted for multicollinearity and bias correction. RESULTS: Dental caries was prevalent among children (83%, 95% confidence interval 79.7–86.0%). Individual factors, including irregular brushing, late adoption of brushing habit, consulting dentist for symptomatic treatment, lack of breast feeding, sleeping with a bottle in mouth, habit of snacking between meals, low consumption of fruits, and frequent consumption of soft drinks and flavored milk, were predominantly associated with dental caries in children, instead of socioeconomic factors (p < 0.05, adjusted R-square 80%). CONCLUSION: Dental caries were prevalent in school children, and individual factors were predominantly associated with the disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12199-018-0750-z) contains supplementary material, which is available to authorized users.",2018 Nov 30,"['Alhabdan, Yazeed Abdullah', 'Albeshr, Abdulhameed Ghassan', 'Yenugadhati, Nagarajkumar', 'Jradi, Hoda']",Environ Health Prev Med,,,True
f3016563bf2b8e925c63a3c6a9e11e287907863c,PMC,Patient factors that affect trust in physicians: a cross-sectional study,http://dx.doi.org/10.1186/s12875-018-0875-6,PMC6267873,30497400,CC BY,"BACKGROUND: While trust in physicians has been rigorously investigated regarding its concept, measurement, and factors, the studies have mainly focused on the attributes of the physicians. This approach can lead to a limited understanding of trust in physicians as trust is based on the relationship, an interaction of both parties: patients and physicians. This study aimed to investigate the factors for trust in physicians among the Koreans by focusing on patients’ traits which are related to their subjective perceptions. METHODS: A web-based survey was conducted between August and September 2016 among 1000 Korean adults aged 18 to 59 years. Survey participants were selected by a proportionate quota sampling based on age, sex and place of residence. The t-test and analysis of variance (ANOVA) were performed to examine the difference in trust in physicians among the different groups in each variable of patient characteristics. An ordinal logistic regression model was employed to examine the association between trust in physicians and patient attributes. RESULTS: Negative health-related traits, such as stress and low self-rated health, were likely to lower trust in physicians, and women were less likely to trust physicians. The negative attitudes toward the current health care system were strongly associated with low trust in physicians. Meanwhile, recent experience of hospitalization or outpatient visit was positively associated with trust in physicians, and experience of not being able to use health facilities showed no significant association. These results suggest that trust in physicians is more likely to be lowered by negative perception than by the objective conditions or experience. CONCLUSION: In investigating the factors for trust in physicians, the patients’ predispositions, which make them less likely to trust physicians, should be considered. The attributes of the patients in Korea, which could negatively affect trust in physicians, need to be investigated in consideration of the recent changes in patient-physician relationships and the medical environment in Korea. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12875-018-0875-6) contains supplementary material, which is available to authorized users.",2018 Nov 29,"['Kim, Agnus M.', 'Bae, Jaekyoung', 'Kang, Sungchan', 'Kim, Yeon-Yong', 'Lee, Jin-Seok']",BMC Fam Pract,,,True
ab179a2dc1b93e7d39b5b371760a3e59da2f2b7e,PMC,Relationship between asymptomatic rotavirus infection and jaundice in neonates: a retrospective study,http://dx.doi.org/10.1186/s12887-018-1352-z,PMC6267884,30501619,CC BY,"BACKGROUND: Rotavirus (RV) infection in neonates can be mild or even asymptomatic. In RV infection, jaundice is often reported, but the relationship between jaundice and RV infection has not been studied. This study aimed to determine the importance of asymptomatic RV screening in neonates with jaundice. METHODS: Neonates from the neonatal intensive care unit (NICU) of Chonbuk National University Hospital, those transferred from local obstetrics and gynecology hospitals and outpatient clinics were selected from 2014 to 2017. The study included only infants aged between 3 and 28 days. Jaundice was defined according to gestational age and birth age, in accordance with the American Academy of Pediatrics guidelines criteria. RV infection was confirmed by a stool test, and RV screening and laboratory tests were performed at admission. RESULTS: Among 596 patients, 166 patients had jaundice. RV infection was observed in 70 (42%) jaundice patients. There were 36 (22%) jaundice patients with asymptomatic RV infection. Patients with onset of jaundice 3–7 days after birth had a high incidence of RV infection. When the RV test was positive, the risk of jaundice was significantly high [odds ratio (OR) 1.89; 95% confidence interval (CI), 1.20–2.98; p = 0.006]. CONCLUSIONS: Infants with the onset of jaundice > 3 days after birth were likely to have RV infection. Therefore, we suggest that screening tests for RV infection be included as part of the evaluation of jaundiced infants presenting to NICU. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12887-018-1352-z) contains supplementary material, which is available to authorized users.",2018 Nov 30,"['Hwang, Nu Ri', 'Kim, Jin Kyu']",BMC Pediatr,,,True
7387ab0ad7fdb62b372043fc912931583e5c7af0,PMC,Co-infection with feline retrovirus is related to changes in immunological parameters of cats with sporotrichosis,http://dx.doi.org/10.1371/journal.pone.0207644,PMC6267967,30500849,CC BY,"Feline sporotrichosis due to Sporothrix brasiliensis is frequently severe and often correlated to zoonotic transmission. Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) cause immunodeficiency in cats; no association has been identified with critical cases of sporotrichosis. Moreover, the cytokine profile in Sporothrix-infected cats and a potential impact of retrovirus co-infections on their immunity is unknown. This study assessed immunological parameters in cats with sporotrichosis with and without FIV or FeLV co-infection. FeLV infection was detected by antigen ELISA and by provirus PCR. FIV infection was investigated through ELISA and Western blot. Cytokine transcription (IFN-γ, IL-4, IL-5, IL-6, IL-10, IL-12, TNF-α) was quantified using RT-qPCR and lymphocyte subpopulations (CD4, CD8, CD5 and CD21) were assessed by flow cytometry. Thirty cats with sporotrichosis were recruited to the study, including three FIV-positive and five FeLV-positive (progressive infection) cats. One cat with regressive FeLV infection was excluded from statistics. In comparison to retrovirus-negative cats, FIV-positive cats and FeLV-positive cats had higher IL-10 levels, FeLV-positive cats had lower IL-4 levels and FIV-positive cats had lower IL-12 levels and a lower CD4+/CD8+ ratio. Remarkably, all cats with poor general condition were FeLV (progressive infection) or FIV-positive, but the retrovirus status was not associated with the sporotrichosis treatment length or outcome. The immunological changes and the more severe clinical presentation observed in cats with retrovirus co-infections encourage future prospective studies that address the impact of these changes on prognostic determinants of feline sporotrichosis and the development of new therapy strategies that control disease spread.",2018 Nov 30,"['de Miranda, Luisa Helena Monteiro', 'Meli, Marina', 'Conceição-Silva, Fátima', 'Novacco, Marilisa', 'Menezes, Rodrigo Caldas', 'Pereira, Sandro Antonio', 'Sugiarto, Sarah', 'dos Reis, Érica Guerino', 'Gremião, Isabella Dib Ferreira', 'Hofmann-Lehmann, Regina']",PLoS One,,,True
a40f0baaa8d1450af8f21422d3623abe288f7cd8,PMC,Antimicrobial and Antioxidant Activities of Essential Oils of Satureja thymbra Growing Wild in Libya,http://dx.doi.org/10.3390/molecules17054836,PMC6268410,22538487,CC BY,"The composition of essential oil isolated from Satureja thymbra, growing wild in Libya, was analyzed by GC and GC-MS. The essential oil was characterized by γ-terpinene (39.23%), thymol (25.16%), p-cymene (7.17%) and carvacrol (4.18%) as the major constituents. Antioxidant activity was analyzed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. It possessed strong antioxidant activity (IC50 = 0.0967 mg/mL). The essential oil was also screened for its antimicrobial activity against eight bacterial and eight fungal species, showing excellent antimicrobial activity against the microorganisms used, in particular against the fungi. The oil of S. thymbra showed bacteriostatic activity at 0.001–0.1 mg/mL and was bactericidal at 0.002–0.2 mg/mL; fungistatic effects at 0.001–0.025 mg/mL and fungicidal effects at 0.001–0.1 mg/mL. The main constituents thymol, carvacrol and γ-terpinene also showed strong antimicrobial activity. The commercial fungicide bifonazole showed much lower antifungal activity than the tested oil.",2012 Apr 26,"['Giweli, Abdulhmid', 'Džamić, Ana M.', 'Soković, Marina', 'Ristić, Mihailo S.', 'Marin, Petar D.']",Molecules,,,True
b272687e1bbab9fefce2b87887609a88e6ecd860,PMC,Fluorescence-Based Multiplex Protein Detection Using Optically Encoded Microbeads,http://dx.doi.org/10.3390/molecules17032474,PMC6268487,22382526,CC BY,"Potential utilization of proteins for early detection and diagnosis of various diseases has drawn considerable interest in the development of protein-based multiplex detection techniques. Among the various techniques for high-throughput protein screening, optically-encoded beads combined with fluorescence-based target monitoring have great advantages over the planar array-based multiplexing assays. This review discusses recent developments of analytical methods of screening protein molecules on microbead-based platforms. These include various strategies such as barcoded microbeads, molecular beacon-based techniques, and surface-enhanced Raman scattering-based techniques. Their applications for label-free protein detection are also addressed. Especially, the optically-encoded beads such as multilayer fluorescence beads and SERS-encoded beads are successful for generating a large number of coding.",2012 Mar 1,"['Jun, Bong-Hyun', 'Kang, Homan', 'Lee, Yoon-Sik', 'Jeong, Dae Hong']",Molecules,,,True
e372562d7379dd73d838995bc9178634c865ba39,PMC,Enhancement of Gene Silencing Effect and Membrane Permeability by Peptide-Conjugated 27-Nucleotide Small Interfering RNA,http://dx.doi.org/10.3390/molecules170911089,PMC6268710,22983148,CC BY,"Two different sizes of siRNAs, of which one type was 21-nucleotide (nt) siRNA containing 2-nt dangling ends and the other type was 27-nt siRNA with blunt ends, were conjugated with a nuclear export signal peptide of HIV-1 Rev at the 5′-sense end. Processing by Dicer enzyme, cell membrane permeability, and RNAi efficiency of the peptide-conjugated siRNAs were examined. Dicer cleaved the peptide-conjugated 27-nt siRNA leading to the release of 21-nt siRNA, whereas the peptide-conjugated 21-nt siRNA was not cleaved. High membrane permeability and cytoplasmic localization was found in the conjugates. Moreover, the peptide-conjugated 27-nt siRNA showed increased potency of RNAi in comparison with the nonmodified 21-nt and 27-nt siRNAs, whereas the peptide-conjugated 21-nt siRNA showed decreased RNAi efficacy. This potent RNAi efficacy is probably owing to acceleration of RISC through recognition by Dicer, as well as to the improvement of cell membrane permeability and intracellular accumulation.",2012 Sep 14,"['Kubo, Takanori', 'Yanagihara, Kazuyoshi', 'Sato, Yuichiro', 'Morita, Yasuhiro', 'Seyama, Toshio']",Molecules,,,True
27d79d16bc5eee9c79ee05ee5997d031e15d72bb,PMC,"Parallel Synthesis of Peptide-Like Macrocycles Containing Imidazole-4,5-dicarboxylic Acid",http://dx.doi.org/10.3390/molecules17055346,PMC6268944,22569415,CC BY,"We prepared a series of peptide-like 14-membered macrocycles containing an imidazole-4,5-dicarboxylic acid scaffold by using known coupling reagents and protecting group strategies. Yields of the purified macrocycles were poor on average, yet seemingly independent of amino acid substitution or stereochemistry. The macrocycles retain some level of conformational variability as observed by both molecular modeling and X-ray crystallography. These macrocycles represent a new class of structures for further development and for future application in high-throughput screening against a variety of biological targets.",2012 May 8,"['Xu, Zhigang', 'Wheeler, Kraig A.', 'Baures, Paul W.']",Molecules,,,True
6fded82a77fe985a107827f07dd5b56a93811b2b,PMC,"Parallel Synthesis of Peptide-Like Macrocycles Containing Imidazole-4,5-dicarboxylic Acid",http://dx.doi.org/10.3390/molecules17055346,PMC6268944,22569415,CC BY,"We prepared a series of peptide-like 14-membered macrocycles containing an imidazole-4,5-dicarboxylic acid scaffold by using known coupling reagents and protecting group strategies. Yields of the purified macrocycles were poor on average, yet seemingly independent of amino acid substitution or stereochemistry. The macrocycles retain some level of conformational variability as observed by both molecular modeling and X-ray crystallography. These macrocycles represent a new class of structures for further development and for future application in high-throughput screening against a variety of biological targets.",2012 May 8,"['Xu, Zhigang', 'Wheeler, Kraig A.', 'Baures, Paul W.']",Molecules,,,False
7c330dd659e9ae0e248b8dbb9e6f8d886dd61c13,PMC,Bioaerosol Sampling for Respiratory Viruses in Singapore’s Mass Rapid Transit Network,http://dx.doi.org/10.1038/s41598-018-35896-1,PMC6269463,30504827,CC BY,"As a leading global city with a high population density, Singapore is at risk for the introduction of novel biological threats. This risk has been recently reinforced by human epidemics in Singapore of SARS coronavirus, 2009 pandemic H1N1 influenza A virus, and enterovirus 71. Other major threats to Singapore include MERS-coronavirus and various avian and swine influenza viruses. The ability to quickly identify and robustly track such threats to initiate an early emergency response remains a significant challenge. In an effort to enhance respiratory virus surveillance in Singapore, our team conducted a pilot study employing a noninvasive bioaerosol sampling method to detect respiratory viruses in Singapore’s Mass Rapid Transit (MRT) network. Over a period of 52 weeks, 89 aerosol samples were collected during peak MRT ridership hours. Nine (10%) tested positive for adenovirus, four (4.5%) tested positive for respiratory syncytial virus type A, and one (1%) tested positive for influenza A virus using real-time RT-PCR/PCR. To our knowledge, this is the first time molecular evidence for any infectious respiratory agent has been collected from Singapore’s MRT. Our pilot study data support the possibility of employing bioaerosol samplers in crowded public spaces to noninvasively monitor for respiratory viruses circulating in communities.",2018 Nov 30,"['Coleman, Kristen K.', 'Nguyen, Tham T.', 'Yadana, Su', 'Hansen-Estruch, Christophe', 'Lindsley, William G.', 'Gray, Gregory C.']",Sci Rep,,,True
1455bb070334751379d26c7c161a1f17b8d07a0c,PMC,"Antimalarial Activity of 4-Metoxychalcones: Docking Studies as Falcipain/Plasmepsin Inhibitors, ADMET and Lipophilic Efficiency Analysis to Identify a Putative Oral Lead Candidate",http://dx.doi.org/10.3390/molecules181215276,PMC6269736,24335577,CC BY,"Herein, we report the antimalarial activity of nine 4-methoxychalcone derivatives 1a–i and an initial analysis of their ADMET properties. All compounds showed potent activity against the P. falciparum chloroquine-resistant clone W2, with IC(50) values ranging from 1.96 µM to 10.99 µM, with moderate or low cytotoxicity against the HeLa cell line. The compound 1a (IC(50) = 2.06 µM) had the best selectivity index (9.0). All the sulfonamide 4-metychalcone derivatives synthesized had cLogP values between 2 and 5 (mean value 3.79) and molecular weights (MWs) below 500. The substitution of the pyrrolidine group in 1i by a morpholine group in 1a reduced the cLogP value from 3.05 in compound 1i to 2.34 in compound 1a. Indeed, compound 1a had the highest LipE value. The binding free energy of compound 1a showed it to be the most optimal chalcone derivative for plasmepsin-2 (−7.3 Kcal/mol). The physicochemical properties and LipE analysis of the dataset allowed us to establish that compound 1a is the highest quality compound of the series and a potential oral lead candidate.",2013 Dec 10,"['de Oliveira, Michael Eder', 'Cenzi, Gisele', 'Nunes, Renata Rachide', 'Andrighetti, Carla Regina', 'de Sousa Valadão, Denia Mendes', 'dos Reis, Cláudia', 'Simões, Cláudia Maria Oliveira', 'Nunes, Ricardo José', 'Júnior, Moacyr Comar', 'Taranto, Alex Gutterres', 'Sanchez, Bruno Antonio Marinho', 'Viana, Gustavo Henrique Ribeiro', 'de Pilla Varotti, Fernando']",Molecules,,,True
62f01258c5feeb75f8e3e3d628f5094b4b20b8c8,PMC,In Vitro and in Vivo Studies of the Inhibitory Effects of Emodin Isolated from Polygonum cuspidatum on Coxsakievirus B(4),http://dx.doi.org/10.3390/molecules181011842,PMC6269740,24071990,CC BY,"The lack of effective therapeutics for Coxsackievirus B(4) (CVB(4)) infection underscores the importance of finding novel antiviral compounds. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is one of the natural anthraquinone derivatives obtained from the root and rhizome of Polygonum cuspidatum. In the present study, the possibility of using emodin as a potential antiviral to treat CVB(4) infection was explored in vitro and in mice. Emodin reduced CVB(4) entry and replication on Hep-2 cells in a concentration- and time-dependent manner, with a 50% effective concentration (EC(50)) of 12.06 μM and selectivity index (SI) of 5.08, respectively. The inhibitory effect of emodin for CVB(4) entry and replication was further confirmed by a quantitative real time PCR (qPCR) assay. The results further showed that the mice orally treated with different dosages of emodin displayed a dose dependent increase of survival rate, body weight and prolonged mean time of death (MTD), accompanied by significantly decreased myocardial virus titers and pathologic scores/lesions. Moreover, emodin could inhibit CVB(4)-induced apoptosis in vitro and in vivo. Our results indicated that emodin could be used as potential antiviral in the post-exposure prophylaxis for CVB(4) infection.",2013 Sep 25,"['Liu, Zhao', 'Wei, Fei', 'Chen, Liang-Jun', 'Xiong, Hai-Rong', 'Liu, Yuan-Yuan', 'Luo, Fan', 'Hou, Wei', 'Xiao, Hong', 'Yang, Zhan-Qiu']",Molecules,,,True
190505ad74408b21fea8434a44a2f43b1ef198b7,PMC,A Facile Synthesis of Deaza-Analogues of the Bisindole Marine Alkaloid Topsentin,http://dx.doi.org/10.3390/molecules18032518,PMC6269752,23442928,CC BY,"A series of substituted ethyl 1-[(tert-butoxycarbonyl)amino]-2-methyl-5-(1-methyl-1H-indol-3-yl)-4-[(1-methyl-1H-indol-3-yl)carbonyl]-1H-pyrrole-3-carboxylates were prepared in excellent yields (82-98%) by one-pot reactions between β-dicarbonyl compounds 12a–e and 1,2-diaza-1,3-diene (DD) 13. Derivatives 10a,c–e, deazaanalogues of the bis-indole alkaloid topsentin, screened by the National Cancer Institute (Bethesda, MD, USA) in the in vitro one dose primary anticancer assay against a panel of about 60 human tumor cell lines, showed no significant activity, with the exception of compound 9e, which showed moderate activity against the HOP-92 cell line of the non small cell lung cancer sub-panel and the SNB-75 cell line of the CNS sub-panel.",2013 Feb 26,"['Carbone, Anna', 'Spanò, Virginia', 'Parrino, Barbara', 'Ciancimino, Cristina', 'Attanasi, Orazio A.', 'Favi, Gianfranco']",Molecules,,,True
4a5e7d2f1256d0aed03adae0c98c5bb522e28748,PMC,In Vitro Evaluation of Novel Inhibitors against the NS2B-NS3 Protease of Dengue Fever Virus Type 4,http://dx.doi.org/10.3390/molecules181215600,PMC6269914,24352016,CC BY,"The discovery of potent therapeutic compounds against dengue virus is urgently needed. The NS2B-NS3 protease (NS2B-NS3(pro)) of dengue fever virus carries out all enzymatic activities needed for polyprotein processing and is considered to be amenable to antiviral inhibition by analogy. Virtual screening of 300,000 compounds using Autodock 3 on the GVSS platform was conducted to identify novel inhibitors against the NS2B-NS3(pro). Thirty-six compounds were selected for in vitro assay against NS2B-NS3(pro) expressed in Pichia pastoris. Seven novel compounds were identified as inhibitors with IC(50) values of 3.9 ± 0.6–86.7 ± 3.6 μM. Three strong NS2B-NS3(pro) inhibitors were further confirmed as competitive inhibitors with K(i) values of 4.0 ± 0.4, 4.9 ± 0.3, and 3.4 ± 0.1 μM, respectively. Hydrophobic and hydrogen bond interactions between amino acid residues in the NS3(pro) active site with inhibition compounds were also identified.",2013 Dec 13,"['Nguyen, Thi Thanh Hanh', 'Lee, Sun', 'Wang, Hsi-Kai', 'Chen, Hsin-Yen', 'Wu, Ying-Ta', 'Lin, Simon C.', 'Kim, Do-Won', 'Kim, Doman']",Molecules,,,True
3dd25c4d762b5123ae356a4c5497f7196af5cd97,PMC,In Vitro Evaluation of Novel Inhibitors against the NS2B-NS3 Protease of Dengue Fever Virus Type 4,http://dx.doi.org/10.3390/molecules181215600,PMC6269914,24352016,CC BY,"The discovery of potent therapeutic compounds against dengue virus is urgently needed. The NS2B-NS3 protease (NS2B-NS3(pro)) of dengue fever virus carries out all enzymatic activities needed for polyprotein processing and is considered to be amenable to antiviral inhibition by analogy. Virtual screening of 300,000 compounds using Autodock 3 on the GVSS platform was conducted to identify novel inhibitors against the NS2B-NS3(pro). Thirty-six compounds were selected for in vitro assay against NS2B-NS3(pro) expressed in Pichia pastoris. Seven novel compounds were identified as inhibitors with IC(50) values of 3.9 ± 0.6–86.7 ± 3.6 μM. Three strong NS2B-NS3(pro) inhibitors were further confirmed as competitive inhibitors with K(i) values of 4.0 ± 0.4, 4.9 ± 0.3, and 3.4 ± 0.1 μM, respectively. Hydrophobic and hydrogen bond interactions between amino acid residues in the NS3(pro) active site with inhibition compounds were also identified.",2013 Dec 13,"['Nguyen, Thi Thanh Hanh', 'Lee, Sun', 'Wang, Hsi-Kai', 'Chen, Hsin-Yen', 'Wu, Ying-Ta', 'Lin, Simon C.', 'Kim, Do-Won', 'Kim, Doman']",Molecules,,,False
f14e7b5fff3c2ac074e61beacf4fb1bba524e438,PMC,"Anti-Inflammatory and Anti-Allergic Activities of Pentaherb Formula, Moutan Cortex (Danpi) and Gallic Acid",http://dx.doi.org/10.3390/molecules18032483,PMC6270292,23439564,CC BY,"Pentaherb formula (PHF) has been proven to improve the quality of life of children with atopic dermatitis without side effects. The aim of this study was to elucidate the potential anti-inflammatory and anti-allergic activities of PHF, Moutan Cortex (Danpi/DP) and gallic acid (GA) using human basophils (KU812 cells), which are crucial effector cells in allergic inflammation. PHF, DP and GA could significantly suppress the expression of allergic inflammatory cytokine IL-33-upregulated intercellular adhesion molecule (ICAM)-1, and the release of chemokines CCL2, CCL5, CXCL8 and inflammatory cytokine IL-6 from KU812 cells (all p < 0.05). With the combined use of dexamethasone (0.01 μg/mL) and GA (10 μg/mL), the suppression of ICAM-1 expression and CCL5 and IL-6 release of IL-33-activated KU812 cells were significantly greater than the use of GA alone (all p < 0.05). The suppression of the IL-33-induced activation of intracellular signalling molecules p38 mitogen activated protein kinase, nuclear factor-κB and c-Jun amino-terminal kinase in GA-treated KU812 cells could be the underlying mechanism for the suppression on ICAM-1, chemokines and cytokines. The combined use of dexamethasone with the natural products PHF or DP or GA might therefore enhance the development of a novel therapeutic modality for allergic inflammatory diseases with high potency and fewer side effects.",2013 Feb 25,"['Liu, Kelly Y. P.', 'Hu, Shuiqing', 'Chan, Ben C. L.', 'Wat, Elaine C. L.', 'Lau, Clara B. S.', 'Hon, Kam L.', 'Fung, Kwok P.', 'Leung, Ping C.', 'Hui, Patrick C. L.', 'Lam, Christopher W. K.', 'Wong, Chun K.']",Molecules,,,True
601a2a29ef252c46e3a3b19f35d1d6fb591b0af6,PMC,Schiff Bases: A Short Survey on an Evergreen Chemistry Tool,http://dx.doi.org/10.3390/molecules181012264,PMC6270622,24108395,CC BY,"The review reports a short biography of the Italian naturalized chemist Hugo Schiff and an outline on the synthesis and use of his most popular discovery: the imines, very well known and popular as Schiff Bases. Recent developments on their “metallo-imines” variants have been described. The applications of Schiff bases in organic synthesis as partner in Staudinger and hetero Diels-Alder reactions, as “privileged” ligands in the organometallic complexes and as biological active Schiff intermediates/targets have been reported as well.",2013 Oct 8,"['Qin, Wenling', 'Long, Sha', 'Panunzio, Mauro', 'Biondi, Stefano']",Molecules,,,True
0edb041a9c7495be584434f3eb3298f3f8a1327c,PMC,Current and Potential Applications of Bismuth-Based Drugs,http://dx.doi.org/10.3390/molecules190915258,PMC6271281,25251194,CC BY,"Bismuth compounds have been used extensively as medicines and in particular for the treatment of gastrointestinal ailments. In addition to bismuth’s well known gastroprotective effects and efficacy in treating H. pylori infection it also has broad anti-microbial, anti-leishmanial and anti-cancer properties. Aspects of the biological chemistry of bismuth are discussed and biomolecular targets associated with bismuth treatment are highlighted. This review strives to provide the reader with an up to date account of bismuth-based drugs currently used to treat patients and discuss potential medicinal applications of bismuth drugs with reference to recent developments in the literature. Ultimately this review aims to encourage original contributions to this exciting and important field.",2014 Sep 23,"['Keogan, Donal M.', 'Griffith, Darren M.']",Molecules,,,True
e1ac05796a8f9ecfb55f2b105d4d1dc359a39fd4,PMC,"Hinokinin, an Emerging Bioactive Lignan",http://dx.doi.org/10.3390/molecules190914862,PMC6271885,25232707,CC BY,"Hinokinin is a lignan isolated from several plant species that has been recently investigated in order to establish its biological activities. So far, its cytotoxicity, its anti-inflammatory and antimicrobial activities have been studied. Particularly interesting is its notable anti-trypanosomal activity.",2014 Sep 17,"['Marcotullio, Maria Carla', 'Pelosi, Azzurra', 'Curini, Massimo']",Molecules,,,True
3fae11ec9abada619c2f2ea754eba8d43e9924d9,PMC,Two Methods for Increased Specificity and Sensitivity in Loop-Mediated Isothermal Amplification,http://dx.doi.org/10.3390/molecules20046048,PMC6272222,25853320,CC BY,"The technique of loop-mediated isothermal amplification (LAMP) utilizes four (or six) primers targeting six (or eight) regions within a fairly small segment of a genome for amplification, with concentration higher than that used in traditional PCR methods. The high concentrations of primers used leads to an increased likelihood of non-specific amplification induced by primer dimers. In this study, a set of LAMP primers were designed targeting the prfA gene sequence of Listeria monocytogenes, and dimethyl sulfoxide (DMSO) as well as Touchdown LAMP were employed to increase the sensitivity and specificity of the LAMP reactions. The results indicate that the detection limit of this novel LAMP assay with the newly designed primers and additives was 10 fg per reaction, which is ten-fold more sensitive than a commercial Isothermal Amplification Kit and hundred-fold more sensitive than previously reported LAMP assays. This highly sensitive LAMP assay has been shown to detect 11 strains of Listeria monocytogenes, and does not detect other Listeria species (including Listeria innocua and Listeria invanovii), providing some advantages in specificity over commercial Isothermal Amplification Kits and previously reported LAMP assay.",2015 Apr 7,"['Wang, De-Guo', 'Brewster, Jeffrey D.', 'Paul, Moushumi', 'Tomasula, Peggy M.']",Molecules,,,True
deda9e69d8455166370e8bd96c2bdb630c4b97b0,PMC,Emerging Structural Insights into Glycoprotein Quality Control Coupled with N-Glycan Processing in the Endoplasmic Reticulum,http://dx.doi.org/10.3390/molecules20022475,PMC6272264,25647580,CC BY,"In the endoplasmic reticulum (ER), the sugar chain is initially introduced onto newly synthesized proteins as a triantennary tetradecasaccharide (Glc(3)Man(9)GlcNAc(2)). The attached oligosaccharide chain is subjected to stepwise trimming by the actions of specific glucosidases and mannosidases. In these processes, the transiently expressed N-glycans, as processing intermediates, function as signals for the determination of glycoprotein fates, i.e., folding, transport, or degradation through interactions of a series of intracellular lectins. The monoglucosylated glycoforms are hallmarks of incompletely folded states of glycoproteins in this system, whereas the outer mannose trimming leads to ER-associated glycoprotein degradation. This review outlines the recently emerging evidence regarding the molecular and structural basis of this glycoprotein quality control system, which is regulated through dynamic interplay among intracellular lectins, glycosidases, and glycosyltransferase. Structural snapshots of carbohydrate-lectin interactions have been provided at the atomic level using X-ray crystallographic analyses. Conformational ensembles of uncomplexed triantennary high-mannose-type oligosaccharides have been characterized in a quantitative manner using molecular dynamics simulation in conjunction with nuclear magnetic resonance spectroscopy. These complementary views provide new insights into glycoprotein recognition in quality control coupled with N-glycan processing.",2015 Jan 30,"['Satoh, Tadashi', 'Yamaguchi, Takumi', 'Kato, Koichi']",Molecules,,,True
59d3750e2fc06cf47e64fbe18dd09649750e05cf,PMC,Current Understanding of Molecular Pathology and Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy,http://dx.doi.org/10.3390/molecules20058823,PMC6272314,25988613,CC BY,"Duchenne muscular dystrophy (DMD) is a genetic muscle disorder caused by mutations in the Dmd gene resulting in the loss of the protein dystrophin. Patients do not only experience skeletal muscle degeneration, but also develop severe cardiomyopathy by their second decade, one of the main causes of death. The absence of dystrophin in the heart renders cardiomyocytes more sensitive to stretch-induced damage. Moreover, it pathologically alters intracellular calcium (Ca(2+)) concentration, neuronal nitric oxide synthase (nNOS) localization and mitochondrial function and leads to inflammation and necrosis, all contributing to the development of cardiomyopathy. Current therapies only treat symptoms and therefore the need for targeting the genetic defect is immense. Several preclinical therapies are undergoing development, including utrophin up-regulation, stop codon read-through therapy, viral gene therapy, cell-based therapy and exon skipping. Some of these therapies are undergoing clinical trials, but these have predominantly focused on skeletal muscle correction. However, improving skeletal muscle function without addressing cardiac aspects of the disease may aggravate cardiomyopathy and therefore it is essential that preclinical and clinical focus include improving heart function. This review consolidates what is known regarding molecular pathology of the DMD heart, specifically focusing on intracellular Ca(2+), nNOS and mitochondrial dysregulation. It briefly discusses the current treatment options and then elaborates on the preclinical therapeutic approaches currently under development to restore dystrophin thereby improving pathology, with a focus on the heart.",2015 May 15,"['van Westering, Tirsa L. E.', 'Betts, Corinne A.', 'Wood, Matthew J. A.']",Molecules,,,True
02da3b3b4a31f4e15f06a0f076524bea9ab0f92a,PMC,Discovery of Metal Ions Chelator Quercetin Derivatives with Potent Anti-HCV Activities,http://dx.doi.org/10.3390/molecules20046978,PMC6272327,25913935,CC BY,"Analogues or isosteres of α,γ-diketoacid (DKA) 1a show potent inhibition of hepatitis C virus (HCV) NS5B polymerase through chelation of the two magnesium ions at the active site. The anti-HCV activity of the flavonoid quercetin (2) could partly be attributed to it being a structural mimic of DKAs. In order to delineate the structural features required for the inhibitory effect and improve the anti-HCV potency, two novel types of quercetin analogues, 7-O-arylmethylquercetins and quercetin-3-O-benzoic acid esters, were designed, synthesized and evaluated for their anti-HCV properties in cell-based assays. Among the 38 newly synthesized compounds, 7-O-substituted derivative 3i and 3-O-substituted derivative 4f were found to be the most active in the corresponding series (EC(50) = 3.8 μM and 9.0 μΜ, respectively). Docking studies suggested that the quercetin analogues are capable of establishing key coordination with the two magnesium ions as well as interactions with residues at the active site of HCV NS5B.",2015 Apr 16,"['Zhong, Dongwei', 'Liu, Mingming', 'Cao, Yang', 'Zhu, Yelin', 'Bian, Shihui', 'Zhou, Jiayi', 'Wu, Fengjie', 'Ryu, Kum-Chol', 'Zhou, Lu', 'Ye, Deyong']",Molecules,,,True
6b5c2baaee6ff05e786184cc2e7b28effca0984f,PMC,Discovery of Metal Ions Chelator Quercetin Derivatives with Potent Anti-HCV Activities,http://dx.doi.org/10.3390/molecules20046978,PMC6272327,25913935,CC BY,"Analogues or isosteres of α,γ-diketoacid (DKA) 1a show potent inhibition of hepatitis C virus (HCV) NS5B polymerase through chelation of the two magnesium ions at the active site. The anti-HCV activity of the flavonoid quercetin (2) could partly be attributed to it being a structural mimic of DKAs. In order to delineate the structural features required for the inhibitory effect and improve the anti-HCV potency, two novel types of quercetin analogues, 7-O-arylmethylquercetins and quercetin-3-O-benzoic acid esters, were designed, synthesized and evaluated for their anti-HCV properties in cell-based assays. Among the 38 newly synthesized compounds, 7-O-substituted derivative 3i and 3-O-substituted derivative 4f were found to be the most active in the corresponding series (EC(50) = 3.8 μM and 9.0 μΜ, respectively). Docking studies suggested that the quercetin analogues are capable of establishing key coordination with the two magnesium ions as well as interactions with residues at the active site of HCV NS5B.",2015 Apr 16,"['Zhong, Dongwei', 'Liu, Mingming', 'Cao, Yang', 'Zhu, Yelin', 'Bian, Shihui', 'Zhou, Jiayi', 'Wu, Fengjie', 'Ryu, Kum-Chol', 'Zhou, Lu', 'Ye, Deyong']",Molecules,,,False
944c456c9127a0b83f1c01d996b9290c291790f3,PMC,Lectins with Anti-HIV Activity: A Review,http://dx.doi.org/10.3390/molecules20010648,PMC6272367,25569520,CC BY,"Lectins including flowering plant lectins, algal lectins, cyanobacterial lectins, actinomycete lectin, worm lectins, and the nonpeptidic lectin mimics pradimicins and benanomicins, exhibit anti-HIV activity. The anti-HIV plant lectins include Artocarpus heterophyllus (jacalin) lectin, concanavalin A, Galanthus nivalis (snowdrop) agglutinin-related lectins, Musa acuminata (banana) lectin, Myrianthus holstii lectin, Narcissus pseudonarcissus lectin, and Urtica diocia agglutinin. The anti-HIV algal lectins comprise Boodlea coacta lectin, Griffithsin, Oscillatoria agardhii agglutinin. The anti-HIV cyanobacterial lectins are cyanovirin-N, scytovirin, Microcystis viridis lectin, and microvirin. Actinohivin is an anti-HIV actinomycete lectin. The anti-HIV worm lectins include Chaetopterus variopedatus polychaete marine worm lectin, Serpula vermicularis sea worm lectin, and C-type lectin Mermaid from nematode (Laxus oneistus). The anti-HIV nonpeptidic lectin mimics comprise pradimicins and benanomicins. Their anti-HIV mechanisms are discussed.",2015 Jan 6,"['Akkouh, Ouafae', 'Ng, Tzi Bun', 'Singh, Senjam Sunil', 'Yin, Cuiming', 'Dan, Xiuli', 'Chan, Yau Sang', 'Pan, Wenliang', 'Cheung, Randy Chi Fai']",Molecules,,,True
4b6f64a80fb18cd5fa4b165916603d65bc6514e2,PMC,QSAR-Assisted Virtual Screening of Lead-Like Molecules from Marine and Microbial Natural Sources for Antitumor and Antibiotic Drug Discovery,http://dx.doi.org/10.3390/molecules20034848,PMC6272462,25789820,CC BY,"A Quantitative Structure-Activity Relationship (QSAR) approach for classification was used for the prediction of compounds as active/inactive relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1746 compounds from PubChem with empirical CDK descriptors and semi-empirical quantum-chemical descriptors. A data set of 183 active pharmaceutical ingredients was additionally used for the external validation of the best models. The best classification models for antibiotic and antitumor activities were used to screen a data set of marine and microbial natural products from the AntiMarin database—25 and four lead compounds for antibiotic and antitumor drug design were proposed, respectively. The present work enables the presentation of a new set of possible lead like bioactive compounds and corroborates the results of our previous investigations. By other side it is shown the usefulness of quantum-chemical descriptors in the discrimination of biologically active and inactive compounds. None of the compounds suggested by our approach have assigned non-antibiotic and non-antitumor activities in the AntiMarin database and almost all were lately reported as being active in the literature.",2015 Mar 17,"['Pereira, Florbela', 'Latino, Diogo A. R. S.', 'Gaudêncio, Susana P.']",Molecules,,,True
59ae1705d9fe9d34f1d7996bea46a83eacf92f47,PMC,"Synthesis, Characterization, Crystal Structure and Antimicrobial Activity of Copper(II) Complexes with the Schiff Base Derived from 2-Hydroxy-4-Methoxybenzaldehyde",http://dx.doi.org/10.3390/molecules20045771,PMC6272500,25849802,CC BY,"A novel Schiff base, ethyl 4-[(E)-(2-hydroxy-4-methoxyphenyl)methylene-amino]benzoate (HL), was prepared and structurally characterized on the basis of elemental analyses, (1)H NMR, (13)C NMR, UV-Vis and IR spectral data. Six new copper(II) complexes, [Cu(L)(NO(3))(H(2)O)(2)] (1), [Cu(L)(2)] (2), [Cu(L)(OAc)] (3), [Cu(2) (L)(2)Cl(2)(H(2)O)(4)] (4), [Cu(L)(ClO(4))(H(2)O)] (5) and [Cu(2)(L(2)S)(ClO(4))(H(2)O)]ClO(4)·H(2)O (6) have been synthesized. The characterization of the newly formed compounds was done by IR, UV-Vis, EPR, FAB mass spectroscopy, elemental and thermal analysis, magnetic susceptibility measurements and molar electric conductivity. The crystal structures of Schiff base and the complex [Cu(2)(L(2)S)(ClO(4))(H(2)O)]ClO(4)·H(2)O (6) have been determined by single crystal X-ray diffraction studies. Both copper atoms display a distorted octahedral coordination type [O(4)NS]. This coordination is ensured by three phenol oxygen, two of which being related to the µ-oxo-bridge, the nitrogen atoms of the azomethine group and the sulfur atoms that come from the polydentate ligand. The in vitro antimicrobial activity against Escherichia coli ATCC 25922, Salmonella enteritidis, Staphylococcus aureus ATCC 25923, Enterococcus and Candida albicans strains was studied and compared with that of free ligand. The complexes 1, 2, 5 showed a better antimicrobial activity than the Schiff base against the tested microorganisms.",2015 Apr 2,"['Pahonțu, Elena', 'Ilieș, Diana-Carolina', 'Shova, Sergiu', 'Paraschivescu, Codruța', 'Badea, Mihaela', 'Gulea, Aurelian', 'Roșu, Tudor']",Molecules,,,True
b18142d59403122a9779c33150cc8ad1b2422803,PMC,"Synthesis, Characterization, Crystal Structure and Antimicrobial Activity of Copper(II) Complexes with the Schiff Base Derived from 2-Hydroxy-4-Methoxybenzaldehyde",http://dx.doi.org/10.3390/molecules20045771,PMC6272500,25849802,CC BY,"A novel Schiff base, ethyl 4-[(E)-(2-hydroxy-4-methoxyphenyl)methylene-amino]benzoate (HL), was prepared and structurally characterized on the basis of elemental analyses, (1)H NMR, (13)C NMR, UV-Vis and IR spectral data. Six new copper(II) complexes, [Cu(L)(NO(3))(H(2)O)(2)] (1), [Cu(L)(2)] (2), [Cu(L)(OAc)] (3), [Cu(2) (L)(2)Cl(2)(H(2)O)(4)] (4), [Cu(L)(ClO(4))(H(2)O)] (5) and [Cu(2)(L(2)S)(ClO(4))(H(2)O)]ClO(4)·H(2)O (6) have been synthesized. The characterization of the newly formed compounds was done by IR, UV-Vis, EPR, FAB mass spectroscopy, elemental and thermal analysis, magnetic susceptibility measurements and molar electric conductivity. The crystal structures of Schiff base and the complex [Cu(2)(L(2)S)(ClO(4))(H(2)O)]ClO(4)·H(2)O (6) have been determined by single crystal X-ray diffraction studies. Both copper atoms display a distorted octahedral coordination type [O(4)NS]. This coordination is ensured by three phenol oxygen, two of which being related to the µ-oxo-bridge, the nitrogen atoms of the azomethine group and the sulfur atoms that come from the polydentate ligand. The in vitro antimicrobial activity against Escherichia coli ATCC 25922, Salmonella enteritidis, Staphylococcus aureus ATCC 25923, Enterococcus and Candida albicans strains was studied and compared with that of free ligand. The complexes 1, 2, 5 showed a better antimicrobial activity than the Schiff base against the tested microorganisms.",2015 Apr 2,"['Pahonțu, Elena', 'Ilieș, Diana-Carolina', 'Shova, Sergiu', 'Paraschivescu, Codruța', 'Badea, Mihaela', 'Gulea, Aurelian', 'Roșu, Tudor']",Molecules,,,False
0f7d645dea0f766fefcd547a1b4a9ec29d2533cd,PMC,The Roles of Direct Recognition by Animal Lectins in Antiviral Immunity and Viral Pathogenesis,http://dx.doi.org/10.3390/molecules20022272,PMC6272511,25642837,CC BY,"Lectins are a group of proteins with carbohydrate recognition activity. Lectins are categorized into many families based on their different cellular locations as well as their specificities for a variety of carbohydrate structures due to the features of their carbohydrate recognition domain (CRD) modules. Many studies have indicated that the direct recognition of particular oligosaccharides on viral components by lectins is important for interactions between hosts and viruses. Herein, we aim to globally review the roles of this recognition by animal lectins in antiviral immune responses and viral pathogenesis. The different classes of mammalian lectins can either recognize carbohydrates to activate host immunity for viral elimination or can exploit those carbohydrates as susceptibility factors to facilitate viral entry, replication or assembly. Additionally, some arthropod C-type lectins were recently identified as key susceptibility factors that directly interact with multiple viruses and then facilitate infection. Summarization of the pleiotropic roles of direct viral recognition by animal lectins will benefit our understanding of host-virus interactions and could provide insight into the role of lectins in antiviral drug and vaccine development.",2015 Jan 29,"['Liu, Yang', 'Liu, Jianying', 'Pang, Xiaojing', 'Liu, Tao', 'Ning, Zhijie', 'Cheng, Gong']",Molecules,,,True
567be8096ec201b856ef35be5cc2c096f64e5fda,PMC,Human Lectins and Their Roles in Viral Infections,http://dx.doi.org/10.3390/molecules20022229,PMC6272597,25642836,CC BY,"Innate recognition of virus proteins is an important component of the immune response to viral pathogens. A component of this immune recognition is the family of lectins; pattern recognition receptors (PRRs) that recognise viral pathogen-associated molecular patterns (PAMPs) including viral glycoproteins. In this review we discuss the contribution of soluble and membrane-associated PRRs to immunity against virus pathogens, and the potential role of these molecules in facilitating virus replication. These processes are illustrated with examples of viruses including human immunodeficiency virus (HIV), hepatitis C virus (HCV) and Ebola virus (EBOV). We focus on the structure, function and genetics of the well-characterised C-type lectin mannose-binding lectin, the ficolins, and the membrane-bound CD209 proteins expressed on dendritic cells. The potential for lectin-based antiviral therapies is also discussed.",2015 Jan 29,"['Mason, Christopher P.', 'Tarr, Alexander W.']",Molecules,,,True
d75b9ec5230fea9af4abc83383da97a102230cfd,PMC,Delivery of RNAi Therapeutics to the Airways—From Bench to Bedside,http://dx.doi.org/10.3390/molecules21091249,PMC6272875,27657028,CC BY,"RNA interference (RNAi) is a potent and specific post-transcriptional gene silencing process. Since its discovery, tremendous efforts have been made to translate RNAi technology into therapeutic applications for the treatment of different human diseases including respiratory diseases, by manipulating the expression of disease-associated gene(s). Similar to other nucleic acid-based therapeutics, the major hurdle of RNAi therapy is delivery. Pulmonary delivery is a promising approach of delivering RNAi therapeutics directly to the airways for treating local conditions and minimizing systemic side effects. It is a non-invasive route of administration that is generally well accepted by patients. However, pulmonary drug delivery is a challenge as the lungs pose a series of anatomical, physiological and immunological barriers to drug delivery. Understanding these barriers is essential for the development an effective RNA delivery system. In this review, the different barriers to pulmonary drug delivery are introduced. The potential of RNAi molecules as new class of therapeutics, and the latest preclinical and clinical studies of using RNAi therapeutics in different respiratory conditions are discussed in details. We hope this review can provide some useful insights for moving inhaled RNAi therapeutics from bench to bedside.",2016 Sep 20,"['Qiu, Yingshan', 'Lam, Jenny K. W.', 'Leung, Susan W. S.', 'Liang, Wanling']",Molecules,,,True
ddcf8a29af29bdb7e62b35517fef0b0754e59f4f,PMC,Asteltoxins with Antiviral Activities from the Marine Sponge-Derived Fungus Aspergillus sp. SCSIO XWS02F40,http://dx.doi.org/10.3390/molecules21010034,PMC6272915,26712735,CC BY,"Two new asteltoxins named asteltoxin E (2) and F (3), and a new chromone (4), together with four known compounds were isolated from a marine sponge–derived fungus, Aspergillus sp. SCSIO XWS02F40. The structures of the compounds (1–7) were determined by the extensive 1D- and 2D-NMR spectra, and HRESIMS spectrometry. All the compounds were tested for their antiviral (H1N1 and H3N2) activity. Compounds 2 and 3 showed significant activity against H3N2 with the prominent IC(50) values of 6.2 ± 0.08 and 8.9 ± 0.3 μM, respectively. In addition, compound 2 also exhibited inhibitory activity against H1N1 with an IC(50) value of 3.5 ± 1.3 μM.",2015 Dec 26,"['Tian, Yong-Qi', 'Lin, Xiu-Ping', 'Wang, Zhen', 'Zhou, Xue-Feng', 'Qin, Xiao-Chu', 'Kaliyaperumal, Kumaravel', 'Zhang, Tian-Yu', 'Tu, Zheng-Chao', 'Liu, Yonghong']",Molecules,,,True
581b8dadae34d680d9fdc435cafb617b47b65739,PMC,Asteltoxins with Antiviral Activities from the Marine Sponge-Derived Fungus Aspergillus sp. SCSIO XWS02F40,http://dx.doi.org/10.3390/molecules21010034,PMC6272915,26712735,CC BY,"Two new asteltoxins named asteltoxin E (2) and F (3), and a new chromone (4), together with four known compounds were isolated from a marine sponge–derived fungus, Aspergillus sp. SCSIO XWS02F40. The structures of the compounds (1–7) were determined by the extensive 1D- and 2D-NMR spectra, and HRESIMS spectrometry. All the compounds were tested for their antiviral (H1N1 and H3N2) activity. Compounds 2 and 3 showed significant activity against H3N2 with the prominent IC(50) values of 6.2 ± 0.08 and 8.9 ± 0.3 μM, respectively. In addition, compound 2 also exhibited inhibitory activity against H1N1 with an IC(50) value of 3.5 ± 1.3 μM.",2015 Dec 26,"['Tian, Yong-Qi', 'Lin, Xiu-Ping', 'Wang, Zhen', 'Zhou, Xue-Feng', 'Qin, Xiao-Chu', 'Kaliyaperumal, Kumaravel', 'Zhang, Tian-Yu', 'Tu, Zheng-Chao', 'Liu, Yonghong']",Molecules,,,False
6d077aec25d3730a6037bf89f1fb73286846fb64,PMC,Saponins from Chinese Medicines as Anticancer Agents,http://dx.doi.org/10.3390/molecules21101326,PMC6272920,27782048,CC BY,"Saponins are glycosides with triterpenoid or spirostane aglycones that demonstrate various pharmacological effects against mammalian diseases. To promote the research and development of anticancer agents from saponins, this review focuses on the anticancer properties of several typical naturally derived triterpenoid saponins (ginsenosides and saikosaponins) and steroid saponins (dioscin, polyphyllin, and timosaponin) isolated from Chinese medicines. These saponins exhibit in vitro and in vivo anticancer effects, such as anti-proliferation, anti-metastasis, anti-angiogenesis, anti-multidrug resistance, and autophagy regulation actions. In addition, related signaling pathways and target proteins involved in the anticancer effects of saponins are also summarized in this work.",2016 Oct 5,"['Xu, Xiao-Huang', 'Li, Ting', 'Fong, Chi Man Vivienne', 'Chen, Xiuping', 'Chen, Xiao-Jia', 'Wang, Yi-Tao', 'Huang, Ming-Qing', 'Lu, Jin-Jian']",Molecules,,,True
eefddcf51f8426ecaa9e3ace144dadfb34a74cf5,PMC,"New Isoxazolidine-Conjugates of Quinazolinones—Synthesis, Antiviral and Cytostatic Activity",http://dx.doi.org/10.3390/molecules21070959,PMC6273226,27455228,CC BY,"A novel series of (3-diethoxyphosphoryl)isoxazolidines substituted at C5 with various quinazolinones have been synthesized by the 1,3-dipolar cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N3-substitued 2-vinyl-3H-quinazolin-4-ones. All isoxazolidines were assessed for antiviral activity against a broad range of DNA and RNA viruses. Isoxazolidines trans-11f/cis-11f (90:10), trans-11h and trans-11i/cis-11i (97:3) showed weak activity (EC(50) = 6.84, 15.29 and 9.44 μM) toward VZV (TK(+) strain) which was only one order of magnitude lower than that of acyclovir used as a reference drug. Phosphonates trans-11b/cis-11b (90:10), trans-11c, trans-11e/cis-11e (90:10) and trans-11g appeared slightly active toward cytomegalovirus (EC(50) = 27–45 μM). Compounds containing benzyl substituents at N3 in the quinazolinone skeleton exhibited slight antiproliferative activity towards the tested immortalized cells with IC(50) in the 21–102 μM range.",2016 Jul 22,"['Piotrowska, Dorota G.', 'Andrei, Graciela', 'Schols, Dominique', 'Snoeck, Robert', 'Grabkowska-Drużyc, Magdalena']",Molecules,,,True
85402ac2e722579c8954fe2da0202d958a578df3,PMC,"New Isoxazolidine-Conjugates of Quinazolinones—Synthesis, Antiviral and Cytostatic Activity",http://dx.doi.org/10.3390/molecules21070959,PMC6273226,27455228,CC BY,"A novel series of (3-diethoxyphosphoryl)isoxazolidines substituted at C5 with various quinazolinones have been synthesized by the 1,3-dipolar cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N3-substitued 2-vinyl-3H-quinazolin-4-ones. All isoxazolidines were assessed for antiviral activity against a broad range of DNA and RNA viruses. Isoxazolidines trans-11f/cis-11f (90:10), trans-11h and trans-11i/cis-11i (97:3) showed weak activity (EC(50) = 6.84, 15.29 and 9.44 μM) toward VZV (TK(+) strain) which was only one order of magnitude lower than that of acyclovir used as a reference drug. Phosphonates trans-11b/cis-11b (90:10), trans-11c, trans-11e/cis-11e (90:10) and trans-11g appeared slightly active toward cytomegalovirus (EC(50) = 27–45 μM). Compounds containing benzyl substituents at N3 in the quinazolinone skeleton exhibited slight antiproliferative activity towards the tested immortalized cells with IC(50) in the 21–102 μM range.",2016 Jul 22,"['Piotrowska, Dorota G.', 'Andrei, Graciela', 'Schols, Dominique', 'Snoeck, Robert', 'Grabkowska-Drużyc, Magdalena']",Molecules,,,False
6bb112bc662ab0ff3a6f44b4f28873c12228c641,PMC,"Advanced Nanobiomaterials: Vaccines, Diagnosis and Treatment of Infectious Diseases",http://dx.doi.org/10.3390/molecules21070867,PMC6273484,27376260,CC BY,"The use of nanoparticles has contributed to many advances due to their important properties such as, size, shape or biocompatibility. The use of nanotechnology in medicine has great potential, especially in medical microbiology. Promising data show the possibility of shaping immune responses and fighting severe infections using synthetic materials. Different studies have suggested that the addition of synthetic nanoparticles in vaccines and immunotherapy will have a great impact on public health. On the other hand, antibiotic resistance is one of the major concerns worldwide; a recent report of the World Health Organization (WHO) states that antibiotic resistance could cause 300 million deaths by 2050. Nanomedicine offers an innovative tool for combating the high rates of resistance that we are fighting nowadays, by the development of both alternative therapeutic and prophylaxis approaches and also novel diagnosis methods. Early detection of infectious diseases is the key to a successful treatment and the new developed applications based on nanotechnology offer an increased sensibility and efficiency of the diagnosis. The aim of this review is to reveal and discuss the main advances made on the science of nanomaterials for the prevention, diagnosis and treatment of infectious diseases. Highlighting innovative approaches utilized to: (i) increasing the efficiency of vaccines; (ii) obtaining shuttle systems that require lower antibiotic concentrations; (iii) developing coating devices that inhibit microbial colonization and biofilm formation.",2016 Jul 1,"['Torres-Sangiao, Eva', 'Holban, Alina Maria', 'Gestal, Monica Cartelle']",Molecules,,,True
5bf6b6685fadbbc4899faa052321c697190bbade,PMC,18α-Glycyrrhetinic Acid Induces Apoptosis of HL-60 Human Leukemia Cells through Caspases- and Mitochondria-Dependent Signaling Pathways,http://dx.doi.org/10.3390/molecules21070872,PMC6273602,27376261,CC BY,"In this study we investigate the molecular mechanisms of caspases and mitochondria in the extrinsic and intrinsic signal apoptosis pathways in human leukemia HL-60 cells after in vitro exposure to 18α-glycyrrhetinic acid (18α-GA). Cells were exposed to 18α-GA at various concentrations for various time periods and were harvested for flow cytometry total viable cell and apoptotic cell death measurements. Cells treated with 18α-GA significantly inhibited cell proliferation and induced cell apoptosis in a dose-dependent manner, with an IC(50) value of 100 μM at 48 h. The cell growth inhibition resulted in induction of apoptosis and decreased the mitochondria membrane potential (ΔΨ(m)) and increased caspase-8, -9 and -3 activities. Furthermore, cytochrome c and AIF were released from mitochondria, as shown by western blotting and confirmed by confocal laser microscopy. Western blotting showed that 18α-GA increased the levels of pro-apoptotic proteins such as Bax and Bid and decreased the anti-apoptotic proteins such as Bcl-2 and Bcl-xl, furthermore, results also showed that 18α-GA increased Fas and Fas-L which are associated with surface death receptor in HL-60 cells. Based on those observations, the present study supports the hypothesis that 18α-GA-induced apoptosis in HL-60 cells involves the activation of the both extrinsic and intrinsic apoptotic pathways.",2016 Jul 1,"['Huang, Yi-Chang', 'Kuo, Chao-Lin', 'Lu, Kung-Wen', 'Lin, Jen-Jyh', 'Yang, Jiun-Long', 'Wu, Rick Sai-Chuen', 'Wu, Ping-Ping', 'Chung, Jing-Gung']",Molecules,,,True
cc5d4948fd9cd097469fbd4a6ee3ca4da5c4593c,PMC,"Synthesis and the Biological Activity of Phosphonylated 1,2,3-Triazolenaphthalimide Conjugates",http://dx.doi.org/10.3390/molecules21111420,PMC6273621,27792200,CC BY,"A novel series of diethyl {4-[(5-substituted-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates designed as analogues of amonafide was synthesized. All phosphonates were assessed for antiviral activity against a broad range of DNA and RNA viruses and several of them showed potency against varicella-zoster virus (VZV) [EC(50) (50% effective concentration) = 27.6–91.5 μM]. Compound 16b exhibited the highest activity against a thymidine kinase-deficient (TK(−)) VZV strain (EC(50) = 27.59 μM), while 16d was the most potent towards TK(+) VZV (EC(50) = 29.91 μM). Cytostatic properties of the compounds 14a–i–17a–i were studied on L1210, CEM, HeLa and HMEC-1 cell lines and most of them were slightly cytostatic for HeLa [IC(50) (50% inhibitory concentration) = 29–130 µM] and L1210 cells [IC(50) (50% inhibitory concentration) = 14–142 µM].",2016 Oct 26,"['Głowacka, Iwona E.', 'Gulej, Rafał', 'Grzonkowski, Piotr', 'Andrei, Graciela', 'Schols, Dominique', 'Snoeck, Robert', 'Piotrowska, Dorota G.']",Molecules,,,True
3e5668500c3bdc49bb0a1689019793b74c624407,PMC,Anti-Inflammatory Effect of Quercetin on RAW 264.7 Mouse Macrophages Induced with Polyinosinic-Polycytidylic Acid,http://dx.doi.org/10.3390/molecules21040450,PMC6273652,27049378,CC BY,"Quercetin (3,3′,4′,5,6-pentahydroxyflavone) is a well-known antioxidant and a flavonol found in many fruits, leaves, and vegetables. Quercetin also has known anti-inflammatory effects on lipopolysaccharide-induced macrophages. However, the effects of quercetin on virus-induced macrophages have not been fully reported. In this study, the anti-inflammatory effect of quercetin on double-stranded RNA (dsRNA)-induced macrophages was examined. Quercetin at concentrations up to 50 μM significantly inhibited the production of NO, IL-6, MCP-1, IP-10, RANTES, GM-CSF, G-CSF, TNF-α, LIF, LIX, and VEGF as well as calcium release in dsRNA (50 µg/mL of polyinosinic-polycytidylic acid)-induced RAW 264.7 mouse macrophages (p < 0.05). Quercetin at concentrations up to 50 μM also significantly inhibited mRNA expression of signal transducer and activated transcription 1 (STAT1) and STAT3 in dsRNA-induced RAW 264.7 cells (p < 0.05). In conclusion, quercetin had alleviating effects on viral inflammation based on inhibition of NO, cytokines, chemokines, and growth factors in dsRNA-induced macrophages via the calcium-STAT pathway.",2016 Apr 4,"['Kim, Young-Jin', 'Park, Wansu']",Molecules,,,True
2590692fa24c429d02c8d67f6100a132c3915473,PMC,"Design, Synthesis and Biological Evaluation of Novel Primaquine-Cinnamic Acid Conjugates of the Amide and Acylsemicarbazide Type",http://dx.doi.org/10.3390/molecules21121629,PMC6273687,27916811,CC BY,"In this paper design and synthesis of a scaffold comprising primaquine (PQ) motif and cinnamic acid derivatives (CADs) bound directly (compounds 3a–k) or via a spacer (compounds 7a–k) are reported. In the first series of compounds, PQ and various CADs were connected by amide bonds and in the second series by acylsemicarbazide functional groups built from the PQ amino group, CONHNH spacer and the carbonyl group originating from the CADs. PQ-CAD amides 3a–k were prepared by a simple one-step condensation reaction of PQ with a series of CAD chlorides (method A) or benzotriazolides 2 (method B). The synthesis of acylsemicarbazides 7a–k included activation of PQ with benzotriazole, preparation of PQ-semicarbazide 6 and its condensation with CAD chlorides 4. All synthesized PQ-CAD conjugates were evaluated for their anticancer, antiviral and antioxidative activities. Almost all compounds from series 3 were selective towards the MCF-7 cell line and active at micromolar concentrations. The o-fluoro derivative 3h showed high activity against HeLa, MCF-7 and in particular against the SW 620 cell line, while acylsemicarbazide 7f with a benzodioxole ring and 7c, 7g and especially 7j with methoxy-, chloro- or trifluoromethyl-substituents in the para position showed high selectivity and high inhibitory activity against MCF-7 cell line at micromolar (7c, 7f, 7g) and nanomolar (7j) levels. Acylsemicarbazide derivatives with trifluoromethyl group(s) 7i, 7j and 7k showed specific activity against human coronavirus (229E) at concentrations which did not alter the normal cell morphology. The same compounds exerted the most potent reducing activity in the DPPH test, together with 7d and 7g, while methoxy (compounds 7c–e), benzodioxole (7f), p-Cl (7g) and m-CF(3) (7i) acylsemicarbazides and amide 3f presented the highest LP inhibition (83%–89%). The dimethoxy derivative 7d was the most potent LOX inhibitor (IC(50) = 10 μΜ). The performed biological tests gave evidence of acylsemicarbazide functional group as superior binding group in PQ-CAD conjugates.",2016 Nov 28,"['Pavić, Kristina', 'Perković, Ivana', 'Gilja, Petra', 'Kozlina, Filip', 'Ester, Katja', 'Kralj, Marijeta', 'Schols, Dominique', 'Hadjipavlou-Litina, Dimitra', 'Pontiki, Eleni', 'Zorc, Branka']",Molecules,,,True
fd738b997979c4b38c3a9aaa1b148a090fe94613,PMC,"Design, Synthesis and Biological Evaluation of Novel Primaquine-Cinnamic Acid Conjugates of the Amide and Acylsemicarbazide Type",http://dx.doi.org/10.3390/molecules21121629,PMC6273687,27916811,CC BY,"In this paper design and synthesis of a scaffold comprising primaquine (PQ) motif and cinnamic acid derivatives (CADs) bound directly (compounds 3a–k) or via a spacer (compounds 7a–k) are reported. In the first series of compounds, PQ and various CADs were connected by amide bonds and in the second series by acylsemicarbazide functional groups built from the PQ amino group, CONHNH spacer and the carbonyl group originating from the CADs. PQ-CAD amides 3a–k were prepared by a simple one-step condensation reaction of PQ with a series of CAD chlorides (method A) or benzotriazolides 2 (method B). The synthesis of acylsemicarbazides 7a–k included activation of PQ with benzotriazole, preparation of PQ-semicarbazide 6 and its condensation with CAD chlorides 4. All synthesized PQ-CAD conjugates were evaluated for their anticancer, antiviral and antioxidative activities. Almost all compounds from series 3 were selective towards the MCF-7 cell line and active at micromolar concentrations. The o-fluoro derivative 3h showed high activity against HeLa, MCF-7 and in particular against the SW 620 cell line, while acylsemicarbazide 7f with a benzodioxole ring and 7c, 7g and especially 7j with methoxy-, chloro- or trifluoromethyl-substituents in the para position showed high selectivity and high inhibitory activity against MCF-7 cell line at micromolar (7c, 7f, 7g) and nanomolar (7j) levels. Acylsemicarbazide derivatives with trifluoromethyl group(s) 7i, 7j and 7k showed specific activity against human coronavirus (229E) at concentrations which did not alter the normal cell morphology. The same compounds exerted the most potent reducing activity in the DPPH test, together with 7d and 7g, while methoxy (compounds 7c–e), benzodioxole (7f), p-Cl (7g) and m-CF(3) (7i) acylsemicarbazides and amide 3f presented the highest LP inhibition (83%–89%). The dimethoxy derivative 7d was the most potent LOX inhibitor (IC(50) = 10 μΜ). The performed biological tests gave evidence of acylsemicarbazide functional group as superior binding group in PQ-CAD conjugates.",2016 Nov 28,"['Pavić, Kristina', 'Perković, Ivana', 'Gilja, Petra', 'Kozlina, Filip', 'Ester, Katja', 'Kralj, Marijeta', 'Schols, Dominique', 'Hadjipavlou-Litina, Dimitra', 'Pontiki, Eleni', 'Zorc, Branka']",Molecules,,,True
582d6fa298f66400e7059dae69cb5d3449144b0d,PMC,New Potential Pharmacological Functions of Chinese Herbal Medicines via Regulation of Autophagy,http://dx.doi.org/10.3390/molecules21030359,PMC6274228,26999089,CC BY,"Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as misfolded proteins or damaged organelles. Defects in autophagy are implicated in the pathogenesis of diseases including cancers, myopathy, neurodegenerations, infections and cardiovascular diseases. In the recent decade, traditional drugs with new clinical applications are not only commonly found in Western medicines, but also highlighted in Chinese herbal medicines (CHM). For instance, pharmacological studies have revealed that active components or fractions from Chaihu (Radix bupleuri), Hu Zhang (Rhizoma polygoni cuspidati), Donglingcao (Rabdosia rubesens), Hou po (Cortex magnoliae officinalis) and Chuan xiong (Rhizoma chuanxiong) modulate cancers, neurodegeneration and cardiovascular disease via autophagy. These findings shed light on the potential new applications and formulation of CHM decoctions via regulation of autophagy. This article reviews the roles of autophagy in the pharmacological actions of CHM and discusses their new potential clinical applications in various human diseases.",2016 Mar 17,"['Law, Betty Yuen Kwan', 'Mok, Simon Wing Fai', 'Wu, An Guo', 'Lam, Christopher Wai Kei', 'Yu, Margaret Xin Yi', 'Wong, Vincent Kam Wai']",Molecules,,,True
6c3d20fd2c5c86c813cddcaef028a3c5f6d7cf34,PMC,iPPBS-Opt: A Sequence-Based Ensemble Classifier for Identifying Protein-Protein Binding Sites by Optimizing Imbalanced Training Datasets,http://dx.doi.org/10.3390/molecules21010095,PMC6274413,26797600,CC BY,"Knowledge of protein-protein interactions and their binding sites is indispensable for in-depth understanding of the networks in living cells. With the avalanche of protein sequences generated in the postgenomic age, it is critical to develop computational methods for identifying in a timely fashion the protein-protein binding sites (PPBSs) based on the sequence information alone because the information obtained by this way can be used for both biomedical research and drug development. To address such a challenge, we have proposed a new predictor, called iPPBS-Opt, in which we have used: (1) the K-Nearest Neighbors Cleaning (KNNC) and Inserting Hypothetical Training Samples (IHTS) treatments to optimize the training dataset; (2) the ensemble voting approach to select the most relevant features; and (3) the stationary wavelet transform to formulate the statistical samples. Cross-validation tests by targeting the experiment-confirmed results have demonstrated that the new predictor is very promising, implying that the aforementioned practices are indeed very effective. Particularly, the approach of using the wavelets to express protein/peptide sequences might be the key in grasping the problem’s essence, fully consistent with the findings that many important biological functions of proteins can be elucidated with their low-frequency internal motions. To maximize the convenience of most experimental scientists, we have provided a step-by-step guide on how to use the predictor’s web server (http://www.jci-bioinfo.cn/iPPBS-Opt) to get the desired results without the need to go through the complicated mathematical equations involved.",2016 Jan 19,"['Jia, Jianhua', 'Liu, Zi', 'Xiao, Xuan', 'Liu, Bingxiang', 'Chou, Kuo-Chen']",Molecules,,,True
1cc48a462dcee201a5ee2786fc2295504ca0543f,PMC,iPPBS-Opt: A Sequence-Based Ensemble Classifier for Identifying Protein-Protein Binding Sites by Optimizing Imbalanced Training Datasets,http://dx.doi.org/10.3390/molecules21010095,PMC6274413,26797600,CC BY,"Knowledge of protein-protein interactions and their binding sites is indispensable for in-depth understanding of the networks in living cells. With the avalanche of protein sequences generated in the postgenomic age, it is critical to develop computational methods for identifying in a timely fashion the protein-protein binding sites (PPBSs) based on the sequence information alone because the information obtained by this way can be used for both biomedical research and drug development. To address such a challenge, we have proposed a new predictor, called iPPBS-Opt, in which we have used: (1) the K-Nearest Neighbors Cleaning (KNNC) and Inserting Hypothetical Training Samples (IHTS) treatments to optimize the training dataset; (2) the ensemble voting approach to select the most relevant features; and (3) the stationary wavelet transform to formulate the statistical samples. Cross-validation tests by targeting the experiment-confirmed results have demonstrated that the new predictor is very promising, implying that the aforementioned practices are indeed very effective. Particularly, the approach of using the wavelets to express protein/peptide sequences might be the key in grasping the problem’s essence, fully consistent with the findings that many important biological functions of proteins can be elucidated with their low-frequency internal motions. To maximize the convenience of most experimental scientists, we have provided a step-by-step guide on how to use the predictor’s web server (http://www.jci-bioinfo.cn/iPPBS-Opt) to get the desired results without the need to go through the complicated mathematical equations involved.",2016 Jan 19,"['Jia, Jianhua', 'Liu, Zi', 'Xiao, Xuan', 'Liu, Bingxiang', 'Chou, Kuo-Chen']",Molecules,,,False
4eb0645a5ab563b06ec101914438267b6552a95e,PMC,Synthesis and Anticancer Activities of Glycyrrhetinic Acid Derivatives,http://dx.doi.org/10.3390/molecules21020199,PMC6274419,26861280,CC BY,"A total of forty novel glycyrrhetinic acid (GA) derivatives were designed and synthesized. The cytotoxic activity of the novel compounds was tested against two human breast cancer cell lines (MCF-7, MDA-MB-231) in vitro by the MTT method. The evaluation results revealed that, in comparison with GA, compound 42 shows the most promising anticancer activity (IC(50) 1.88 ± 0.20 and 1.37 ± 0.18 μM for MCF-7 and MDA-MB-231, respectively) and merits further exploration as a new anticancer agent.",2016 Feb 6,"['Li, Yang', 'Feng, Ling', 'Song, Zhi-Fang', 'Li, Hai-Bei', 'Huai, Qi-Yong']",Molecules,,,True
d73d189618e61f04c6dbabf3bbf8aa7adc65b156,PMC,Theranostics Aspects of Various Nanoparticles in Veterinary Medicine,http://dx.doi.org/10.3390/ijms19113299,PMC6274759,30352960,CC BY,"Nanoscience and nanotechnology shows immense interest in various areas of research and applications, including biotechnology, biomedical sciences, nanomedicine, and veterinary medicine. Studies and application of nanotechnology was explored very extensively in the human medical field and also studies undertaken in rodents extensively, still either studies or applications in veterinary medicine is not up to the level when compared to applications to human beings. The application in veterinary medicine and animal production is still relatively innovative. Recently, in the era of health care technologies, Veterinary Medicine also entered into a new phase and incredible transformations. Nanotechnology has tremendous and potential influence not only the way we live, but also on the way that we practice veterinary medicine and increase the safety of domestic animals, production, and income to the farmers through use of nanomaterials. The current status and advancements of nanotechnology is being used to enhance the animal growth promotion, and production. To achieve these, nanoparticles are used as alternative antimicrobial agents to overcome the usage alarming rate of antibiotics, detection of pathogenic bacteria, and also nanoparticles being used as drug delivery agents as new drug and vaccine candidates with improved characteristics and performance, diagnostic, therapeutic, feed additive, nutrient delivery, biocidal agents, reproductive aids, and finally to increase the quality of food using various kinds of functionalized nanoparticles, such as liposomes, polymeric nanoparticles, dendrimers, micellar nanoparticles, and metal nanoparticles. It seems that nanotechnology is ideal for veterinary applications in terms of cost and the availability of resources. The main focus of this review is describes some of the important current and future principal aspects of involvement of nanotechnology in Veterinary Medicine. However, we are not intended to cover the entire scenario of Veterinary Medicine, despite this review is to provide a glimpse at potential important targets of nanotechnology in the field of Veterinary Medicine. Considering the strong potential of the interaction between the nanotechnology and Veterinary Medicine, the aim of this review is to provide a concise description of the advances of nanotechnology in Veterinary Medicine, in terms of their potential application of various kinds of nanoparticles, secondly we discussed role of nanomaterials in animal health and production, and finally we discussed conclusion and future perspectives of nanotechnology in veterinary medicine.",2018 Oct 24,"['Bai, Ding-Ping', 'Lin, Xin-Yu', 'Huang, Yi-Fan', 'Zhang, Xi-Feng']",Int J Mol Sci,,,True
e08398305bb975e1eeb01ab0f93335347005297f,PMC,DNA Vaccines—How Far From Clinical Use?,http://dx.doi.org/10.3390/ijms19113605,PMC6274812,30445702,CC BY,"Two decades ago successful transfection of antigen presenting cells (APC) in vivo was demonstrated which resulted in the induction of primary adaptive immune responses. Due to the good biocompatibility of plasmid DNA, their cost-efficient production and long shelf life, many researchers aimed to develop DNA vaccine-based immunotherapeutic strategies for treatment of infections and cancer, but also autoimmune diseases and allergies. This review aims to summarize our current knowledge on the course of action of DNA vaccines, and which factors are responsible for the poor immunogenicity in human so far. Important optimization steps that improve DNA transfection efficiency comprise the introduction of DNA-complexing nano-carriers aimed to prevent extracellular DNA degradation, enabling APC targeting, and enhanced endo/lysosomal escape of DNA. Attachment of virus-derived nuclear localization sequences facilitates nuclear entry of DNA. Improvements in DNA vaccine design include the use of APC-specific promotors for transcriptional targeting, the arrangement of multiple antigen sequences, the co-delivery of molecular adjuvants to prevent tolerance induction, and strategies to circumvent potential inhibitory effects of the vector backbone. Successful clinical use of DNA vaccines may require combined employment of all of these parameters, and combination treatment with additional drugs.",2018 Nov 15,"['Hobernik, Dominika', 'Bros, Matthias']",Int J Mol Sci,,,True
826b7e6b690a85314484d1eaf93fb020603b3479,PMC,MicroRNA-221-5p Inhibits Porcine Epidemic Diarrhea Virus Replication by Targeting Genomic Viral RNA and Activating the NF-κB Pathway,http://dx.doi.org/10.3390/ijms19113381,PMC6274926,30380612,CC BY,"MicroRNAs (miRNAs) are a class of noncoding RNAs involved in posttranscriptional regulation of gene expression and many critical roles in numerous biological processes. Porcine epidemic diarrhea virus (PEDV), the etiological agent of porcine epidemic diarrhea, causes substantial economic loss in the swine industry worldwide. Previous studies reported miRNA involvement in viral infection; however, their role in regulating PEDV infection remains unknown. In this study, we investigated the regulatory relationship between miRNA-221-5p and PEDV infection, finding that miR-221-5p overexpression inhibited PEDV replication in a dose-dependent manner, and that silencing endogenous miR-221-5p enhanced viral replication. Our results showed that miR-221-5p directly targets the 3′ untranslated region (UTR) of PEDV genomic RNA to inhibit PEDV replication, and that miR-221-5p overexpression activates nuclear factor (NF)-κB signaling via p65 nuclear translocation, thereby upregulating interferon (IFN)-β, IFN-stimulated gene 15, and MX1 expression during CH/HBTS/2017 infection. We subsequently identified NF-κB-inhibitor α and suppressor of cytokine signaling 1, negative regulators of the NF-κB pathway, as miR-221-5p targets. These results demonstrated the ability of miR-221-5p to inhibit PEDV replication by targeting the 3’ UTR of the viral genome and activating the NF-κB-signaling pathway. Our findings will aid the development of preventive and therapeutic strategies for PEDV infection.",2018 Oct 29,"['Zheng, Hongqing', 'Xu, Lei', 'Liu, Yuzhong', 'Li, Cheng', 'Zhang, Liang', 'Wang, Tao', 'Zhao, Di', 'Xu, Xingang', 'Zhang, Yanming']",Int J Mol Sci,,,True
290408ae0dcc207b221cee5bd2b86763ac593a1b,PMC,Ubiquitin–Proteasome System Is Required for Efficient Replication of Singapore Grouper Iridovirus,http://dx.doi.org/10.3389/fmicb.2018.02798,PMC6275174,30534113,CC BY,"The ubiquitin–proteasome system (UPS) serves as the major intracellular pathway for protein degradation and plays crucial roles in several cellular processes. However, little is known about the potential actions of the UPS during fish virus infection. In this study, we elucidated the possible roles of UPS in the life cycle of Singapore grouper iridovirus (SGIV); a large DNA virus that usually causes serious systemic diseases with high mortality in groupers. Data from transcriptomic analysis of differentially expressed genes illustrated that expression of 65 genes within the UPS pathway, including ubiquitin encoding, ubiquitination, deubiquitination, and proteasome, were up- or down-regulated during SGIV infection. Using different proteasome inhibitors, inhibition of the proteasome decreased SGIV replication in vitro, accompanied by inhibition of virus assembly site formation, and viral gene transcription and protein transportation. Over-expression of ubiquitin partly rescued the inhibitory effect of ubiquitin inhibitor on SGIV replication, suggesting that UPS was required for fish iridovirus infection in vitro. Viral or host proteins regulated by proteasome inhibition during SGIV infection were investigated with two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Sixty-two differentially expressed proteins, including 15 viral and 47 host proteins, were identified after SGIV infection. The host proteins were involved in ubiquitin-mediated protein degradation, metabolism, cytoskeleton, macromolecular biosynthesis, and signal transduction. Among them, 11 proteins were negatively regulated upon MG132 treatment during SGIV infection. This is believed to be the first study to provide evidence that UPS was essential for fish virus infection and replication.",2018 Nov 26,"['Huang, Xiaohong', 'Wei, Shina', 'Ni, Songwei', 'Huang, Youhua', 'Qin, Qiwei']",Front Microbiol,,,True
3ebbe746b0f09acf2bef30ee83a8fb7bb9cdc537,PMC,Artificial MicroRNA-Mediated Inhibition of Japanese Encephalitis Virus Replication in Neuronal Cells,http://dx.doi.org/10.1089/nat.2018.0743,PMC6277082,30457923,CC BY,"Artificial microRNA (amiRNA)-mediated inhibition of viral replication has recently gained importance as a strategy for antiviral therapy. In this study, we evaluated the benefit of using the amiRNA vector against Japanese encephalitis virus (JEV). We designed three single amiRNA sequences against the consensus sequence of 3′ untranslated region (3′UTR) of JEV and tested their efficacy against cell culture-grown JEV Vellore strain (P20778) in neuronal cells. The binding ability of three amiRNAs on 3′UTR region was tested in vitro in HEK293T cells using a JEV 3′UTR tagged with luciferase reporter vector. Transient transfection of amiRNAs was nontoxic to cells as evident from the MTT assay and caused minimal induction in interferon-stimulated gene expression. Furthermore, our result suggested that transient expression of two amiRNAs (amiRNA #1 and amiRNA #2) significantly reduced intracellular viral RNA and nonstructural 1 (NS1) protein, as well as diminished infectious viral particle release up to 95% in the culture supernatant as evident from viral plaque reduction assay. Overall, our results indicated that RNA interference based on amiRNAs targeting viral conserved regions at 3′UTR was a useful approach for improvements of nucleic acid inhibitors against JEV.",2018 Dec 1,"['Sharma, Himani', 'Tripathi, Aarti', 'Kumari, Bharti', 'Vrati, Sudhanshu', 'Banerjee, Arup']",Nucleic Acid Ther,,,True
cb495813627c5daa898a901ef2c076fe8469ea66,PMC,"Prevalence of Common Respiratory Viral Infections and Identification of Adenovirus in Hospitalized Adults in Harbin, China 2014 to 2017",http://dx.doi.org/10.3389/fmicb.2018.02919,PMC6277751,30542337,CC BY,"Background: Respiratory infections pose a great challenge in global health, and the prevalence of viral infection in adult patients has been poorly understood in northeast China. Harbin is one of the major cities in northeast China, and more than half of any given year in Harbin is occupied by winter. To reveal the viral etiology and seasonality in adult patients from Harbin, a 4-year consecutive survey was conducted in Harbin, China. Methods: From January 2014 to December 2017, specimens were obtained from adult patients admitted to the Second Affiliated Hospital of Harbin Medical University with lower respiratory tract infections. Sputum samples were examined by direct immunofluorescence assays to detect seven common respiratory viruses, including influenza virus (type A and B), parainfluenza virus (type 1 to 3), respiratory syncytial virus and adenovirus. Adenovirus positive samples were seeded onto A549 cells to isolate viral strains. Phylogenetic analysis was conducted on the highly variable region of adenoviral hexon gene. Results: A total of 1,300 hospitalized adult patients with lower respiratory tract infections were enrolled, in which 189 patients (14.5%) were detected as having at least one viral infection. The co-infection rate in this study was 25.9% (49/189). The dominant viral pathogen from 2014 to 2017 was parainfluenza virus, with a detection rate of 7.2%, followed by influenza virus, respiratory syncytial virus and adenovirus. Based on the climate seasons determined by daily average temperature, the highest overall viral detection rate was detected in spring (22.0%, 52/236), followed by winter (13.4%, 109/813), autumn (11.4%, 13/114) and summer (10.9%, 15/137). Adenovirus type 3 strains with slight variations were isolated from positive cases, which were closely related to the GB strain from the United States, as well as the Harbin04B strain isolated locally. Conclusion: This study demonstrated that common respiratory viruses were partially responsible for hospitalized lower respiratory tract infections in adult patients from Harbin, China, with parainfluenza virus as the dominant viral pathogen. Climate seasons could be rational indicators for the seasonality analysis of airborne viral infections. Future surveillance on viral mutations would be necessary to reveal the evolutionary history of respiratory viruses.",2018 Nov 27,"['Wang, Yingchen', 'Dong, Tuo', 'Qi, Guiyun', 'Qu, Lixin', 'Liang, Wei', 'Qi, Binbin', 'Zhang, Zhe', 'Shang, Lei', 'Gao, Hong', 'Du, Xiqiao', 'Lu, Bing', 'Guo, Yan', 'Liu, Zhenwei', 'Yu, Huisong', 'Cui, Qi', 'Wang, Xiaocen', 'Li, Ye', 'Guo, Weiyuan', 'Qu, Zhangyi']",Front Microbiol,,,True
80beb71c4b247cf32525097f28568b49f71cf08b,PMC,Glycogen Synthase Kinase 3β Enhances Hepatitis C Virus Replication by Supporting miR-122,http://dx.doi.org/10.3389/fmicb.2018.02949,PMC6278592,30542341,CC BY,"Hepatitis C virus (HCV) infection is associated with alterations in host lipid and insulin signaling cascades, which are partially explained by a dependence of the HCV life cycle on key molecules in these metabolic pathways. Yet, little is known on the role in the HCV life cycle of glycogen synthase kinase 3 (GSK3), one of the most important kinases in cellular metabolism. Therefore, the impact of GSK3 on the HCV life cycle was assessed in human hepatoma cell lines harboring subgenomic genotype 1b and 2a replicons or producing cell culture-derived HCV genotype 2a by exposure to synthetic GSK3 inhibitors, GSK3 gene silencing, overexpression of GSK3 constructs and immunofluorescence analyses. In addition, the role of GSK3 in hepatitis E virus (HEV) replication was investigated to assess virus specificity of the observed findings. We found that both inhibition of GSK3 function by synthetic inhibitors as well as silencing of GSK3β gene expression resulted in a decrease of HCV replication and infectious particle production, whereas silencing of the GSK3α isoform had no relevant effect on the HCV life cycle. Conversely, overexpression of GSK3β resulted in enhanced HCV replication. In contrast, GSK3β had no effect on replication of subgenomic HEV replicon. The pro-viral effect of GSK3β on HCV replication was mediated by supporting expression of microRNA-122 (miR-122), a micro-RNA which is mandatory for wild-type HCV replication, as GSK3 inhibitors suppressed miR-122 levels and as inhibitors of GSK3 had no antiviral effect on a miR-122-independent HCV mutant. In conclusion, we have identified GSK3β is a novel host factor supporting HCV replication by maintaining high levels of hepatic miR-122 expression.",2018 Nov 27,"['Saleh, Maged', 'Rüschenbaum, Sabrina', 'Welsch, Christoph', 'Zeuzem, Stefan', 'Moradpour, Darius', 'Gouttenoire, Jérôme', 'Lange, Christian M.']",Front Microbiol,,,True
5148f1055dda3d084d867a119c10c397fb647c55,PMC,Glycogen Synthase Kinase 3β Enhances Hepatitis C Virus Replication by Supporting miR-122,http://dx.doi.org/10.3389/fmicb.2018.02949,PMC6278592,30542341,CC BY,"Hepatitis C virus (HCV) infection is associated with alterations in host lipid and insulin signaling cascades, which are partially explained by a dependence of the HCV life cycle on key molecules in these metabolic pathways. Yet, little is known on the role in the HCV life cycle of glycogen synthase kinase 3 (GSK3), one of the most important kinases in cellular metabolism. Therefore, the impact of GSK3 on the HCV life cycle was assessed in human hepatoma cell lines harboring subgenomic genotype 1b and 2a replicons or producing cell culture-derived HCV genotype 2a by exposure to synthetic GSK3 inhibitors, GSK3 gene silencing, overexpression of GSK3 constructs and immunofluorescence analyses. In addition, the role of GSK3 in hepatitis E virus (HEV) replication was investigated to assess virus specificity of the observed findings. We found that both inhibition of GSK3 function by synthetic inhibitors as well as silencing of GSK3β gene expression resulted in a decrease of HCV replication and infectious particle production, whereas silencing of the GSK3α isoform had no relevant effect on the HCV life cycle. Conversely, overexpression of GSK3β resulted in enhanced HCV replication. In contrast, GSK3β had no effect on replication of subgenomic HEV replicon. The pro-viral effect of GSK3β on HCV replication was mediated by supporting expression of microRNA-122 (miR-122), a micro-RNA which is mandatory for wild-type HCV replication, as GSK3 inhibitors suppressed miR-122 levels and as inhibitors of GSK3 had no antiviral effect on a miR-122-independent HCV mutant. In conclusion, we have identified GSK3β is a novel host factor supporting HCV replication by maintaining high levels of hepatic miR-122 expression.",2018 Nov 27,"['Saleh, Maged', 'Rüschenbaum, Sabrina', 'Welsch, Christoph', 'Zeuzem, Stefan', 'Moradpour, Darius', 'Gouttenoire, Jérôme', 'Lange, Christian M.']",Front Microbiol,,,False
33813052430b7faada17882d12fc343aad02981e,PMC,"Genomic Analyses of Human European Diversity at the Southwestern Edge: Isolation, African Influence and Disease Associations in the Canary Islands",http://dx.doi.org/10.1093/molbev/msy190,PMC6278859,30289472,CC BY,"Despite the genetic resemblance of Canary Islanders to other southern European populations, their geographical isolation and the historical admixture of aborigines (from North Africa) with sub-Saharan Africans and Europeans have shaped a distinctive genetic makeup that likely affects disease susceptibility and health disparities. Based on single nucleotide polymorphism array data and whole genome sequencing (30×), we inferred that the last African admixture took place ∼14 generations ago and estimated that up to 34% of the Canary Islander genome is of recent African descent. The length of regions in homozygosis and the ancestry-related mosaic organization of the Canary Islander genome support the view that isolation has been strongest on the two smallest islands. Furthermore, several genomic regions showed significant and large deviations in African or European ancestry and were significantly enriched in genes involved in prevalent diseases in this community, such as diabetes, asthma, and allergy. The most prominent of these regions were located near LCT and the HLA, two well-known targets of selection, at which 40‒50% of the Canarian genome is of recent African descent according to our estimates. Putative selective signals were also identified in these regions near the SLC6A11-SLC6A1, KCNMB2, and PCDH20-PCDH9 genes. Taken together, our findings provide solid evidence of a significant recent African admixture, population isolation, and adaptation in this part of Europe, with the favoring of African alleles in some chromosome regions. These findings may have medical implications for populations of recent African ancestry.",2018 Dec 5,"['Guillen-Guio, Beatriz', 'Lorenzo-Salazar, Jose M', 'González-Montelongo, Rafaela', 'Díaz-de Usera, Ana', 'Marcelino-Rodríguez, Itahisa', 'Corrales, Almudena', 'Cabrera de León, Antonio', 'Alonso, Santos', 'Flores, Carlos']",Mol Biol Evol,,,True
87cce3d733ad6f5f0d283d58b8a2b1a0dc47f99e,PMC,Human antibody reaction against recombinant salivary proteins of Phlebotomus orientalis in Eastern Africa,http://dx.doi.org/10.1371/journal.pntd.0006981,PMC6279015,30513081,CC0,"BACKGROUND: Phlebotomus orientalis is a vector of Leishmania donovani, the causative agent of life threatening visceral leishmaniasis spread in Eastern Africa. During blood-feeding, sand fly females salivate into the skin of the host. Sand fly saliva contains a large variety of proteins, some of which elicit specific antibody responses in the bitten hosts. To evaluate the exposure to sand fly bites in human populations from disease endemic areas, we tested the antibody reactions of volunteers' sera against recombinant P. orientalis salivary antigens. METHODOLOGY/PRINCIPAL FINDINGS: Recombinant proteins derived from sequence data on P. orientalis secreted salivary proteins, were produced using either bacterial (five proteins) or mammalian (four proteins) expression systems and tested as antigens applicable for detection of anti-P. orientalis IgG in human sera. Using these recombinant proteins, human sera from Sudan and Ethiopia, countries endemic for visceral leishmaniasis, were screened by ELISA and immunoblotting to identify the potential markers of exposure to P. orientalis bites. Two recombinant proteins; mAG5 and mYEL1, were identified as the most promising antigens showing high correlation coefficients as well as good specificity in comparison to the whole sand fly salivary gland homogenate. Combination of both proteins led to a further increase of correlation coefficients as well as both positive and negative predictive values of P. orientalis exposure. CONCLUSIONS/SIGNIFICANCE: This is the first report of screening human sera for anti-P. orientalis antibodies using recombinant salivary proteins. The recombinant salivary proteins mYEL1 and mAG5 proved to be valid antigens for screening human sera from both Sudan and Ethiopia for exposure to P. orientalis bites. The utilization of equal amounts of these two proteins significantly increased the capability to detect anti-P. orientalis antibody responses.",2018 Dec 4,"['Sumova, Petra', 'Sima, Michal', 'Spitzova, Tatiana', 'Osman, Maha E.', 'Guimaraes-Costa, Anderson B.', 'Oliveira, Fabiano', 'Elnaiem, Dia-Eldin A.', 'Hailu, Asrat', 'Warburg, Alon', 'Valenzuela, Jesus G.', 'Volf, Petr']",PLoS Negl Trop Dis,,,True
d0cd9dce26de5d011fa364f5131d8e40630ead35,PMC,Exploring motivations behind pollution-mask use in a sample of young adults in urban China,http://dx.doi.org/10.1186/s12992-018-0441-y,PMC6280386,30514342,CC BY,"BACKGROUND: Wearing a pollution mask is an effective, practical, and economic way to prevent the inhalation of dangerous particulate matter (PM). However, it is not uncommon to observe negligence in adopting such behaviour, and this especially among young segments of the population. Using the Theory of Planned Behaviour (TPB) as conceptual framework, this study explores the role of socio-cognitive factors that affect the decision of wearing a pollution mask in the context of young educated people. This is done by selecting a sample of college students in urban China, a country that has seen air quality as one of the major challenges in the last decades. While young urban college students might be expected to be receptive to standard attempts to be influenced through reason-based cognitive stimuli, it is often found that this is not the case. The empirical analysis was articulated it in two steps. Structural Equation Modelling (SEM) was first used to examine the relationships among the conceptual constructs derived from the TPB conceptual model, and second Step-Wise Ordinary Least Squares Regressions (SWOLS) were employed to observe the partial effect played by each item on the decision to wear a mask. RESULTS: Results show that, while reason-based stimuli play a role, attitude, social norm, and self-efficacy were the most important predictors of the behavioural intention (p < 0.01). The role of past behaviour was also acknowledged as strongly associated with the dependent variable (p < 0.01). Overall, the likelihood of wearing a pollution mask increases with the importance of others socio-cognitive and psychological factors, which could help understand behavioural biases, and explain the relative role of several mechanisms behind the decision to wear a mask. CONCLUSIONS: While tackling pollution requires multiple and synergic approaches, encouraging self-prevention using pollution mask is a simple and effective action, implementable at negligible costs. Resistance among younger, well-educated cohorts to wear masks can be overcome by stressing the social desirability of action and the sense of empowerment derived from its usage. This study has the potential to inform policies aimed at changing suboptimal behavioural attitudes by identifying triggers for change, and it could serve in improving the tailoring of health promotion messages aimed at nudging healthy behaviour. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12992-018-0441-y) contains supplementary material, which is available to authorized users.",2018 Dec 4,"['Hansstein, Francesca Valeria', 'Echegaray, Fabián']",Global Health,,,True
dcfa47b076db144f586108d35f5d43e5100c02d5,PMC,CHAC1 Is Differentially Expressed in Normal and Cystic Fibrosis Bronchial Epithelial Cells and Regulates the Inflammatory Response Induced by Pseudomonas aeruginosa,http://dx.doi.org/10.3389/fimmu.2018.02823,PMC6282009,30555487,CC BY,"In cystic fibrosis (CF), Pseudomonas aeruginosa (Pa) colonizes the lungs, leading to chronic inflammation of the bronchial epithelium. ChaC glutathione-specific γ-glutamylcyclotransferase 1 (CHAC1) mRNA is differentially expressed in primary human airway epithelial cells from bronchi (hAECBs) from patients with CF and healthy patients at baseline and upon infection with Pa. CHAC1 degrades glutathione and is associated with ER stress and apoptosis pathways. In this study, we examined the roles of CHAC1 in the inflammatory response and apoptosis in lung epithelial cells. First, we confirmed by reverse transcription quantitative polymerase chain reaction that CHAC1 mRNA was overexpressed in hAECBs from patients without CF compared with the expression in hAECBs from patients with CF upon Pa (PAK strain) infection. Moreover, the Pa virulence factors LPS and flagellin were shown to induce CHAC1 expression in cells from patients without CF. Using NCI-H292 lung epithelial cells, we found that LPS-induced CHAC1 mRNA expression was PERK-independent and involved ATF4. Additionally, using CHAC1 small interfering RNA, we showed that reduced CHAC1 expression in the context of LPS and flagellin stimulation was associated with modulation of inflammatory markers and alteration of NF-κB signaling. Finally, we showed that Pa was not able to induce apoptosis in NCI-H292 cells. Our results suggest that CHAC1 is involved in the regulation of inflammation in bronchial cells during Pa infection and may explain the excessive inflammation present in the respiratory tracts of patients with CF.",2018 Nov 29,"['Perra, Léa', 'Balloy, Viviane', 'Foussignière, Tobias', 'Moissenet, Didier', 'Petat, Hortense', 'Mungrue, Imran N.', 'Touqui, Lhousseine', 'Corvol, Harriet', 'Chignard, Michel', 'Guillot, Loic']",Front Immunol,,,True
c533acda4a9bf4bb9a13403ab3c984a2394c659a,PMC,High-yield production of human Dicer by transfection of human HEK293-EBNA1 cells grown in suspension,http://dx.doi.org/10.1186/s12896-018-0485-3,PMC6282390,30522464,CC BY,"BACKGROUND: Dicer is a 219-kDa protein that plays key roles in gene regulation, particularly as the ribonuclease III enzyme responsible for cleaving precursor miRNA substrates. Its enzymatic activity is highly regulated by protein factors, and this regulation can impact on the levels of miRNAs and modulate the behavior of a cell. To better understand the underlying mechanisms of regulation, detailed enzymatic and structural characterization of Dicer are needed. However, these types of studies generally require several milligrams of recombinant protein, and efficient preparation of such quantities of pure human Dicer remains a challenge. To prepare large quantities of human Dicer, we have optimized transfection in HEK293-6E cells grown in suspension and streamlined a purification procedure. RESULTS: Transfection conditions were first optimized to achieve expression levels between 10 and 18 mg of recombinant Dicer per liter of culture. A three-step purification protocol was then developed that yields 4–9 mg of purified Dicer per liter of culture in a single day. From SEC-MALS/RI analysis and negative stain TEM, we confirmed that the purified protein is monomerically pure ( ≥ 98%) and folds with the characteristic L-shape geometry. Using an electrophoretic mobility shift assay, a dissociation constant (K(d)) of 5 nM was measured for Dicer binding to pre-let-7a-1, in agreement with previous reports. However, when probing the cleavage activity of Dicer for pre-let-7a-1, we measured k(cat) (7.2 ± 0.5 min(− 1)) and K(M) (1.2 ± 0.3 μM) values that are much higher than previously reported due to experimental conditions that better respect the steady-state assumption. CONCLUSIONS: The expression and purification protocols described here provide high yields of monomerically pure and active human Dicer. Cleavage studies of a pre-let-7 substrate with this purified Dicer reveal higher k(cat) and K(M) values than previously reported and support the current view that conformational changes are associated with substrate binding. Large quantities of highly pure Dicer will be valuable for future biochemical, biophysical and structural investigations of this key protein of the miRNA pathway. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12896-018-0485-3) contains supplementary material, which is available to authorized users.",2018 Dec 6,"['Bouvette, Jonathan', 'Korkut, Dursun Nizam', 'Fouillen, Aurélien', 'Amellah, Soumiya', 'Nanci, Antonio', 'Durocher, Yves', 'Omichinski, James G.', 'Legault, Pascale']",BMC Biotechnol,,,False
cc4677c77d61de96ba2873ecfc8faa4a2f393def,PMC,High-yield production of human Dicer by transfection of human HEK293-EBNA1 cells grown in suspension,http://dx.doi.org/10.1186/s12896-018-0485-3,PMC6282390,30522464,CC BY,"BACKGROUND: Dicer is a 219-kDa protein that plays key roles in gene regulation, particularly as the ribonuclease III enzyme responsible for cleaving precursor miRNA substrates. Its enzymatic activity is highly regulated by protein factors, and this regulation can impact on the levels of miRNAs and modulate the behavior of a cell. To better understand the underlying mechanisms of regulation, detailed enzymatic and structural characterization of Dicer are needed. However, these types of studies generally require several milligrams of recombinant protein, and efficient preparation of such quantities of pure human Dicer remains a challenge. To prepare large quantities of human Dicer, we have optimized transfection in HEK293-6E cells grown in suspension and streamlined a purification procedure. RESULTS: Transfection conditions were first optimized to achieve expression levels between 10 and 18 mg of recombinant Dicer per liter of culture. A three-step purification protocol was then developed that yields 4–9 mg of purified Dicer per liter of culture in a single day. From SEC-MALS/RI analysis and negative stain TEM, we confirmed that the purified protein is monomerically pure ( ≥ 98%) and folds with the characteristic L-shape geometry. Using an electrophoretic mobility shift assay, a dissociation constant (K(d)) of 5 nM was measured for Dicer binding to pre-let-7a-1, in agreement with previous reports. However, when probing the cleavage activity of Dicer for pre-let-7a-1, we measured k(cat) (7.2 ± 0.5 min(− 1)) and K(M) (1.2 ± 0.3 μM) values that are much higher than previously reported due to experimental conditions that better respect the steady-state assumption. CONCLUSIONS: The expression and purification protocols described here provide high yields of monomerically pure and active human Dicer. Cleavage studies of a pre-let-7 substrate with this purified Dicer reveal higher k(cat) and K(M) values than previously reported and support the current view that conformational changes are associated with substrate binding. Large quantities of highly pure Dicer will be valuable for future biochemical, biophysical and structural investigations of this key protein of the miRNA pathway. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12896-018-0485-3) contains supplementary material, which is available to authorized users.",2018 Dec 6,"['Bouvette, Jonathan', 'Korkut, Dursun Nizam', 'Fouillen, Aurélien', 'Amellah, Soumiya', 'Nanci, Antonio', 'Durocher, Yves', 'Omichinski, James G.', 'Legault, Pascale']",BMC Biotechnol,,,True
84cdd2606c5e32c3573a6c70e5c9b14d22c5acc2,PMC,"The Effect of School Closure on Hand, Foot, and Mouth Disease Transmission in Singapore: A Modeling Approach",http://dx.doi.org/10.4269/ajtmh.18-0099,PMC6283473,30350767,CC BY,"Singapore implements a school closure policy for institutional hand, foot, and mouth disease (HFMD) outbreaks, but there is a lack of empirical evidence on the effect of closure on HFMD transmission. We conducted a retrospective analysis of 197,207 cases of HFMD over the period 2003–2012 at the national level and of 57,502 cases in 10,080 institutional outbreaks over the period 2011–2016 in Singapore. The effects of school closure due to 1) institutional outbreaks, 2) public holidays, and 3) school vacations were assessed using a Bayesian time series modeling approach. School closure was associated with a reduction in HFMD transmission rate. During public holidays, average numbers of secondary cases having onset the week after dropped by 53% (95% credible interval 44–62%), and during school vacations, the number of secondary cases dropped by 7% (95% credible interval 3–10%). Schools being temporarily closed in response to an institutional outbreak reduced the average number of new cases by 1,204 (95% credible interval 1,140–1,297). Despite the positive effect in reducing transmission, the effect of school closure is relatively small and may not justify the routine use of this measure.",2018 Dec 22,"['Chen, Yirong', 'Badaruddin, Hishamuddin', 'Lee, Vernon J.', 'Cutter, Jeffery', 'Cook, Alex R.']",Am J Trop Med Hyg,,,True
c0e24854fa61c8a7441dcb7d756d6cbaa4685507,PMC,"The Effect of School Closure on Hand, Foot, and Mouth Disease Transmission in Singapore: A Modeling Approach",http://dx.doi.org/10.4269/ajtmh.18-0099,PMC6283473,30350767,CC BY,"Singapore implements a school closure policy for institutional hand, foot, and mouth disease (HFMD) outbreaks, but there is a lack of empirical evidence on the effect of closure on HFMD transmission. We conducted a retrospective analysis of 197,207 cases of HFMD over the period 2003–2012 at the national level and of 57,502 cases in 10,080 institutional outbreaks over the period 2011–2016 in Singapore. The effects of school closure due to 1) institutional outbreaks, 2) public holidays, and 3) school vacations were assessed using a Bayesian time series modeling approach. School closure was associated with a reduction in HFMD transmission rate. During public holidays, average numbers of secondary cases having onset the week after dropped by 53% (95% credible interval 44–62%), and during school vacations, the number of secondary cases dropped by 7% (95% credible interval 3–10%). Schools being temporarily closed in response to an institutional outbreak reduced the average number of new cases by 1,204 (95% credible interval 1,140–1,297). Despite the positive effect in reducing transmission, the effect of school closure is relatively small and may not justify the routine use of this measure.",2018 Dec 22,"['Chen, Yirong', 'Badaruddin, Hishamuddin', 'Lee, Vernon J.', 'Cutter, Jeffery', 'Cook, Alex R.']",Am J Trop Med Hyg,,,False
552a4c014407e9ee2861cd1fa3985bff02905411,PMC,"The Effect of School Closure on Hand, Foot, and Mouth Disease Transmission in Singapore: A Modeling Approach",http://dx.doi.org/10.4269/ajtmh.18-0099,PMC6283473,30350767,CC BY,"Singapore implements a school closure policy for institutional hand, foot, and mouth disease (HFMD) outbreaks, but there is a lack of empirical evidence on the effect of closure on HFMD transmission. We conducted a retrospective analysis of 197,207 cases of HFMD over the period 2003–2012 at the national level and of 57,502 cases in 10,080 institutional outbreaks over the period 2011–2016 in Singapore. The effects of school closure due to 1) institutional outbreaks, 2) public holidays, and 3) school vacations were assessed using a Bayesian time series modeling approach. School closure was associated with a reduction in HFMD transmission rate. During public holidays, average numbers of secondary cases having onset the week after dropped by 53% (95% credible interval 44–62%), and during school vacations, the number of secondary cases dropped by 7% (95% credible interval 3–10%). Schools being temporarily closed in response to an institutional outbreak reduced the average number of new cases by 1,204 (95% credible interval 1,140–1,297). Despite the positive effect in reducing transmission, the effect of school closure is relatively small and may not justify the routine use of this measure.",2018 Dec 22,"['Chen, Yirong', 'Badaruddin, Hishamuddin', 'Lee, Vernon J.', 'Cutter, Jeffery', 'Cook, Alex R.']",Am J Trop Med Hyg,,,False
0491cbfb51fc286fa6498b7eb59982d797a39388,PMC,"The Effect of School Closure on Hand, Foot, and Mouth Disease Transmission in Singapore: A Modeling Approach",http://dx.doi.org/10.4269/ajtmh.18-0099,PMC6283473,30350767,CC BY,"Singapore implements a school closure policy for institutional hand, foot, and mouth disease (HFMD) outbreaks, but there is a lack of empirical evidence on the effect of closure on HFMD transmission. We conducted a retrospective analysis of 197,207 cases of HFMD over the period 2003–2012 at the national level and of 57,502 cases in 10,080 institutional outbreaks over the period 2011–2016 in Singapore. The effects of school closure due to 1) institutional outbreaks, 2) public holidays, and 3) school vacations were assessed using a Bayesian time series modeling approach. School closure was associated with a reduction in HFMD transmission rate. During public holidays, average numbers of secondary cases having onset the week after dropped by 53% (95% credible interval 44–62%), and during school vacations, the number of secondary cases dropped by 7% (95% credible interval 3–10%). Schools being temporarily closed in response to an institutional outbreak reduced the average number of new cases by 1,204 (95% credible interval 1,140–1,297). Despite the positive effect in reducing transmission, the effect of school closure is relatively small and may not justify the routine use of this measure.",2018 Dec 22,"['Chen, Yirong', 'Badaruddin, Hishamuddin', 'Lee, Vernon J.', 'Cutter, Jeffery', 'Cook, Alex R.']",Am J Trop Med Hyg,,,False
3222436ea52738f6e055fcc74fdf7ed9da92feef,PMC,Editorial: Emerging Viruses: Host Immunity and Novel Therapeutic Interventions,http://dx.doi.org/10.3389/fimmu.2018.02828,PMC6284039,30555490,CC BY,,2018 Nov 30,"['Smed-Sörensen, Anna', 'Oh, Ding Yuan', 'Oshiumi, Hiroyuki', 'Hsu, Alan Chen-Yu']",Front Immunol,,,False
6085ea96b3a7c381215ba90b26f8664ae7c63178,PMC,"Complete Genome Sequence of a Novel Swine Acute Diarrhea Syndrome Coronavirus, CH/FJWT/2018, Isolated in Fujian, China, in 2018",http://dx.doi.org/10.1128/MRA.01259-18,PMC6284080,30533848,CC BY,"The full-length genome sequence of a novel swine acute diarrhea syndrome coronavirus (SADS-CoV), CH/FJWT/2018, was determined, which was genetically most closely related to CN/GDWT/2017, recently discovered in Fujian, China. The indel sites of the spike (S) gene of CH/FJWT/2018 were most similar to those of bat-origin SADS-related coronaviruses.",2018 Dec 6,"['Li, Kai', 'Li, Hao', 'Bi, Zhen', 'Gu, Jun', 'Gong, Wang', 'Luo, Suxian', 'Zhang, Fanfan', 'Song, Deping', 'Ye, Yu', 'Tang, Yuxin']",Microbiol Resour Announc,,,True
b3d50623bac3bd61b8af9c6dc65fa73e6086e645,PMC,Phospholipase A(2) in skin biology: new insights from gene-manipulated mice and lipidomics,http://dx.doi.org/10.1186/s41232-018-0089-2,PMC6284315,30546811,CC BY,"The skin represents one of the tissues that are most profoundly influenced by alterations in the quality of lipids (lipoquality). Lipids not only constitute cellular membranes, but also serve as bioactive lipid mediators and essential components of the skin barrier. Phospholipase A(2) (PLA(2)) enzymes supply fatty acids and lysophospholipids from membrane phospholipids, thereby variably affecting cutaneous homeostasis. Accordingly, perturbation of particular PLA(2)-driven lipid pathways can be linked to various forms of skin disease. In this review article, we highlight the roles of several PLA(2) subtypes in cutaneous pathophysiology, as revealed by transgenic/knockout studies in combination with comprehensive lipidomics. We focus mainly on secreted PLA(2) group IIF (sPLA(2)-IIF), which is associated with epidermal hyperplasia through mobilization of a unique lipid metabolite. We also address the distinct roles of sPLA(2)-IIE in hair follicles and sPLA(2)-IID in lymphoid immune cells that secondarily affect cutaneous inflammation, and provide some insights into species differences in sPLA(2)s. Additionally, we briefly overview the patatin-like phospholipase PNPLA1, which belongs to the Ca(2+)-independent PLA(2) (iPLA(2)) family, as a key regulator of skin barrier function through catalysis of a unique non-PLA(2) reaction. These knowledges on lipid metabolism driven by various PLA(2) subtypes will open novel opportunities for translated studies toward diagnosis and therapy of human skin diseases.",2018 Dec 7,"['Murakami, Makoto', 'Yamamoto, Kei', 'Taketomi, Yoshitaka']",Inflamm Regen,,,True
1090afa5b76644ce9e3be9d9d0e67ad651f846d9,PMC,Novel broad spectrum virucidal molecules against enveloped viruses,http://dx.doi.org/10.1371/journal.pone.0208333,PMC6285983,30532192,CC BY,"Viral infections are an important cause of death worldwide. Unfortunately, there is still a lack of antiviral drugs or vaccines for a large number of viruses, and this represents a remarkable challenge particularly for emerging and re-emerging viruses. For this reason, the identification of broad spectrum antiviral compounds provides a valuable opportunity for developing efficient antiviral therapies. Here we report on a class of rhodanine and thiobarbituric derivatives displaying a broad spectrum antiviral activity against seven different enveloped viruses including an HSV-2 acyclovir resistant strain with favorable selectivity indexes. Due to their selective action on enveloped viruses and to their lipid oxidation ability, we hypothesize a mechanism on the viral envelope that affects the fluidity of the lipid bilayer, thus compromising the efficiency of virus-cell fusion and preventing viral entry.",2018 Dec 7,"['Cagno, Valeria', 'Tintori, Cristina', 'Civra, Andrea', 'Cavalli, Roberta', 'Tiberi, Marika', 'Botta, Lorenzo', 'Brai, Annalaura', 'Poli, Giulio', 'Tapparel, Caroline', 'Lembo, David', 'Botta, Maurizio']",PLoS One,,,True
dbd121bc5733e77f68826080a177fb8b0e8d3106,PMC,Small-area spatial statistical analysis of malaria clusters and hotspots in Cameroon;2000–2015,http://dx.doi.org/10.1186/s12879-018-3534-6,PMC6286522,30526507,CC BY,"BACKGROUND: Malaria prevalence in Cameroon is a major public health problem both at the regional and urban-rural geographic scale. In 2016, an estimated 1.6 million confirmed cases, and 18,738 cases were reported in health facilities and communities respectively, with about 8000 estimated deaths. Several studies have estimated malaria prevalence in Cameroon using the analytical techniques at the regional scale. We aimed at identifying malaria clusters and hotspots at the urban-rural geographic scale from the Demographic and Health Survey (DHS) data for households between 2000 and 2015 using ArcGIS for intervention programs. METHODS: To identify malaria hotspots and analyze the pattern of distribution, we used the optimized hotspots toolset and spatial autocorrelation respectively in ArcGIS 10.3 for desktop. We also used Pearson’s Correlation analysis to identify associative environmental factors using the R-software 3.4.1. RESULTS: The spatial distribution of malaria showed statistically significant clustered pattern for the year 2000 and 2015 with Moran’s indexes 0.126 (P < 0.001) and 0.187 (P < 0.001) respectively. Meanwhile, the years 2005 and 2010 with Moran’s indexes 0.001 (P = 0.488) and 0.002 (P = 0.318) respectively, had a random malaria distribution pattern. There exist varying degrees of malaria clusters and statistically significant hotspots in the urban-rural areas of the 12 administrative regions. Malaria cases were associated with population density and some environmental covariates; rainfall, enhanced vegetation index and composite lights (P < 0.001). CONCLUSION: This study identified urban-rural areas with high and low malaria clusters and hotspots. Our maps can be used as supportive tools for effective malaria control and elimination, and investments in malaria programs and research, malaria prevention, diagnosis and treatment, surveillance, should pay more attention to urban-rural geographic scale.",2018 Dec 7,"['Tewara, Marlvin Anemey', 'Mbah-Fongkimeh, Prisca Ngetemalah', 'Dayimu, Alimu', 'Kang, Fengling', 'Xue, Fuzhong']",BMC Infect Dis,,,True
894676819b105b56f30438858631fce2958592e0,PMC,"Case-control study of the epidemiological and clinical features of human adenovirus 55 and human adenovirus 7 infection in children with acute lower respiratory tract infections in Beijing, China, 2008–2013",http://dx.doi.org/10.1186/s12879-018-3520-z,PMC6286589,30526511,CC BY,"BACKGROUND: In adults, the emerging human adenovirus (HAdV) type 55 (HAdV-55) has been reported to cause more severe cases of adenovirus induced acute lower respiratory tract infections (ALRTIs) compared to other HAdV serotypes (HAdV-3, HAdV-7, HAdV-14). However, there is a dearth of comparative studies in children that address differences in the clinical epidemiological features between HAdV-55 and other HAdV serotypes that can also induce severe infection (such as HAdV-7). METHODS: We conducted a retrospective review of pediatric patients hospitalized at Beijing Children’s Hospital with ALRTI from April 2008 to December 2013 who had adenovirus detected from nasopharyngeal or throat samples by PCR. We further compared pediatric patients infected with HAdV-55 to those infected with HAdV-7 using a case-control methodology by matching each subject with HAdV-55 infection to 4 patients with HAdV-7 infection within 2 months of each HAdV-55 infection. Demographic, clinical, and etiological data were collected and analyzed. RESULTS: Over the five-year period, HAdV was detected in 194 children. Of these, 8 were HAdV-55 positive. Epidemiological results showed that HAdV-55 infection was observed only in 4% of adenovirus infected children whereas HAdV-7 infection proportioned 53%. Most cases of HAdV-55 infection were identified during March and April, whereas HAdV-7 infection occurred throughout the year. Wheezing was significantly less frequent in the HAdV-55 group. No patients infected with HAdV-55 presented with vomiting or had any underlying disease. Coinfections with other respiratory tract pathogens were frequent among children infected with either HAdV-55 or HAdV-7. CONCLUSIONS: HAdV-55 circulated in Beijing during spring and appeared to cause pediatric respiratory infections that were as severe as HAdV-7 infections. Broader surveillance studies are needed.",2018 Dec 7,"['Xu, Lili', 'Liu, Jun', 'Liu, Chunyan', 'Duan, Yali', 'Zhu, Yun', 'Xu, Baoping', 'Xie, Zhengde']",BMC Infect Dis,,,True
d86a5350811ae89aa7878812f7e74944362dbf2b,PMC,Conservation implications of primate trade in China over 18 years based on web news reports of confiscations,http://dx.doi.org/10.7717/peerj.6069,PMC6286804,30564524,CC BY,"Primate species have been increasingly threatened by legal and illegal trade in China, mainly for biomedical research or as pets and traditional medicine, yet most reports on trade from China regard international trade. To assess a proxy for amount of national primate trades, we quantified the number of reports of native primate species featuring in unique web news reports from 2000 to 2017, including accuracy of their identification, location where they were confiscated or rescued, and their condition upon rescue. To measure temporal trends across these categories, the time span was divided into three sections: 2000–2005, 2006–2011 and 2012–2017. A total of 735 individuals of 14 species were reported in 372 news reports, mostly rhesus macaques (n = 165, 22.5%, Macaca mulatta) and two species of slow lorises (n = 487, 66.3%, Nycticebus spp.). During the same period, live individuals of rhesus macaques were recorded 206 times (70,949 individuals) in the Convention on International Trade in Endangered Species of Wild Fauna and Flora Trade Database, whereas slow lorises were only recorded four times (nine individuals), indicating that the species originated illegally from China or were illegally imported into China. Due to their rescued locations in residential areas (n = 211, 56.7%), most primates appeared to be housed privately as pets. A higher proportion of ‘market’ rescues during 2006–2011 (χ(2) = 8.485, df = 2, p = 0.014), could be partly attributed to an intensive management on wildlife markets since the outbreak of severe acute respiratory syndrome (SARS) in 2003. More than half (68.3%, 502 individuals) of the primate individuals were unhealthy, injured or dead when rescued. Thus, identification and welfare training and capacity-building should be provided to husbandry and veterinary professionals, as well as education to the public through awareness initiatives. The increase in presence of some species, especially slow lorises, with a declining population in restricted areas, also suggests the urgent need for public awareness about the illegal nature of keeping these taxa as pets.",2018 Dec 6,"['Ni, Qingyong', 'Wang, Yu', 'Weldon, Ariana', 'Xie, Meng', 'Xu, Huailiang', 'Yao, Yongfang', 'Zhang, Mingwang', 'Li, Ying', 'Li, Yan', 'Zeng, Bo', 'Nekaris, K.A.I.']",PeerJ,,,True
31491f82bfaa808144e856d7a21308cfa971b558,PMC,Replication of MERS and SARS coronaviruses in bat cells offers insights to their ancestral origins,http://dx.doi.org/10.1038/s41426-018-0208-9,PMC6286955,30531999,CC BY,"Previous findings of Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses in bats, and the ability of Tylonycteris-BatCoV HKU4 spike protein to utilize MERS-CoV receptor, human dipeptidyl peptidase 4 hDPP4, suggest a bat ancestral origin of MERS-CoV. We developed 12 primary bat cell lines from seven bat species, including Tylonycteris pachypus, Pipistrellus abramus and Rhinolophus sinicus (hosts of Tylonycteris-BatCoV HKU4, Pipistrellus-BatCoV HKU5, and SARS-related-CoV respectively), and tested their susceptibilities to MERS-CoVs, SARS-CoV, and human coronavirus 229E (HCoV-229E). Five cell lines, including P. abramus and R. sinicus but not T. pachypus cells, were susceptible to human MERS-CoV EMC/2012. However, three tested camel MERS-CoV strains showed different infectivities, with only two strains capable of infecting three and one cell lines respectively. SARS-CoV can only replicate in R. sinicus cells, while HCoV-229E cannot replicate in any bat cells. Bat dipeptidyl peptidase 4 (DPP4) sequences were closely related to those of human and non-human primates but distinct from dromedary DPP4 sequence. Critical residues for binding to MERS-CoV spike protein were mostly conserved in bat DPP4. DPP4 was expressed in the five bat cells susceptible to MERS-CoV, with significantly higher mRNA expression levels than those in non-susceptible cells (P = 0.0174), supporting that DPP4 expression is critical for MERS-CoV infection in bats. However, overexpression of T. pachypus DPP4 failed to confer MERS-CoV susceptibility in T. pachypus cells, suggesting other cellular factors in determining viral replication. The broad cellular tropism of MERS-CoV should prompt further exploration of host diversity of related viruses to identify its ancestral origin.",2018 Dec 10,"['Lau, Susanna K. P.', 'Fan, Rachel Y. Y.', 'Luk, Hayes K. H.', 'Zhu, Longchao', 'Fung, Joshua', 'Li, Kenneth S. M.', 'Wong, Emily Y. M.', 'Ahmed, Syed Shakeel', 'Chan, Jasper F. W.', 'Kok, Raven K. H.', 'Chan, Kwok-Hung', 'Wernery, Ulrich', 'Yuen, Kwok-Yung', 'Woo, Patrick C. Y.']",Emerg Microbes Infect,,,True
43b6759b989971eb0410fd45e7f97750183ed1bf,PMC,A Method for RNA Structure Prediction Shows Evidence for Structure in lncRNAs,http://dx.doi.org/10.3389/fmolb.2018.00111,PMC6286970,30560136,CC BY,To compare the secondary structure profiles of RNA molecules we developed the CROSSalign method. CROSSalign is based on the combination of the Computational Recognition Of Secondary Structure (CROSS) algorithm to predict the RNA secondary structure profile at single-nucleotide resolution and the Dynamic Time Warping (DTW) method to align profiles of different lengths. We applied CROSSalign to investigate the structural conservation of long non-coding RNAs such as XIST and HOTAIR as well as ssRNA viruses including HIV. CROSSalign performs pair-wise comparisons and is able to find homologs between thousands of matches identifying the exact regions of similarity between profiles of different lengths. In a pool of sequences with the same secondary structure CROSSalign accurately recognizes repeat A of XIST and domain D2 of HOTAIR and outperforms other methods based on covariance modeling. The algorithm is freely available at the webpage http://service.tartaglialab.com//new_submission/crossalign.,2018 Dec 3,"['Delli Ponti, Riccardo', 'Armaos, Alexandros', 'Marti, Stefanie', 'Tartaglia, Gian Gaetano']",Front Mol Biosci,,,True
a69fd3fb91451692a0d45c306bd5c8c7dbc9debd,PMC,Lipid Transporter Activity-Related Genetic Polymorphisms Are Associated With Steroid-Induced Osteonecrosis of the Femoral Head: An Updated Meta-Analysis Based on the GRADE Guidelines,http://dx.doi.org/10.3389/fphys.2018.01684,PMC6287043,30559675,CC BY,"Aims: The purpose of this study was to assess the relationship between genetic variants and steroid-induced osteonecrosis of the femoral head (SONFH) in steroid use populations. Methods: We searched the public databases up to April 15, 2018. This study analyzed only the single-nucleotide polymorphisms (SNPs) that have appeared in more than three studies and assessed the level of evidence by classifying the outcomes according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: The ABCB1 rs1045642 C>T mutation had a protective effect against SONFH in the allelic model (I(2) = 50.2%; OR: 0.74; 95% CI: 0.55–1.00; p = 0.046). The rs2032582 mutation in the ABCB1 gene showed no relationship to SONFH (allelic model: I(2) = 63.4%; OR: 0.85; 95% CI: 0.58–1.23; p = 0.382). In ApoB rs693, four models showed that mutations can increase SONFH risk, but the allelic model did not. The ApoB rs1042031 mutation increased SONFH risk in the dominant model (I(2) = 50.3%; OR: 2.90; 95% CI: 1.49–5.66; p = 0.002). Conclusion: An allelic model of ABCB1 rs1045642 showed that mutations have a protective effect against SONFH at a very low level of evidence. The mutations in ApoB rs693 and rs1042031 increase the SONFH risk with moderate levels of evidence.",2018 Dec 3,"['Chen, Xiantao', 'Zhang, Leilei', 'Liang, Dawei', 'Li, Jing', 'Liu, Fenzhi', 'Ma, Hongxia']",Front Physiol,,,True
f3c95c392092682a084d2d0d7ef7e65473f4433f,PMC,Publisher Correction: Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis,http://dx.doi.org/10.1038/s41598-018-36918-8,PMC6287097,30531867,CC BY,,2018 Dec 10,"['Kirchdoerfer, Robert N.', 'Wang, Nianshuang', 'Pallesen, Jesper', 'Wrapp, Daniel', 'Turner, Hannah L.', 'Cottrell, Christopher A.', 'Corbett, Kizzmekia S.', 'Graham, Barney S.', 'McLellan, Jason S.', 'Ward, Andrew B.']",Sci Rep,,,False
12a4354b2c97189beca7e04d721508f420928396,PMC,The Multiples Fates of the Flavivirus RNA Genome During Pathogenesis,http://dx.doi.org/10.3389/fgene.2018.00595,PMC6288177,30564270,CC BY,"The Flavivirus genus comprises many viruses (including dengue, Zika, West Nile and yellow fever viruses) which constitute important public health concerns worldwide. For several of these pathogens, neither antivirals nor vaccines are currently available. In addition to this unmet medical need, flaviviruses are of particular interest since they constitute an excellent model for the study of spatiotemporal regulation of RNA metabolism. Indeed, with no DNA intermediate or nuclear step, the flaviviral life cycle entirely relies on the cytoplasmic fate of a single RNA species, namely the genomic viral RNA (vRNA) which contains all the genetic information necessary for optimal viral replication. From a single open reading frame, the vRNA encodes a polyprotein which is processed to generate the mature viral proteins. In addition to coding for the viral polyprotein, the vRNA serves as a template for RNA synthesis and is also selectively packaged into newly assembled viral particles. Notably, vRNA translation, replication and encapsidation must be tightly coordinated in time and space via a fine-tuned equilibrium as these processes cannot occur simultaneously and hence, are mutually exclusive. As such, these dynamic processes involve several vRNA secondary and tertiary structures as well as RNA modifications. Finally, the vRNA can be detected as a foreign molecule by cytosolic sensors which trigger upon activation antiviral signaling pathways and the production of antiviral factors such as interferons and interferon-stimulated genes. However, to create an environment favorable to infection, flaviviruses have evolved mechanisms to dampen these antiviral processes, notably through the production of a specific vRNA degradation product termed subgenomic flavivirus RNA (sfRNA). In this review, we discuss the current understanding of the fates of flavivirus vRNA and how this is regulated at the molecular level to achieve an optimal replication within infected cells.",2018 Dec 4,"['Mazeaud, Clément', 'Freppel, Wesley', 'Chatel-Chaix, Laurent']",Front Genet,,,True
1bd1b038d7ed985902aeef21bc1493eda76cdab5,PMC,γδ T Cells Provide Protective Function in Highly Pathogenic Avian H5N1 Influenza A Virus Infection,http://dx.doi.org/10.3389/fimmu.2018.02812,PMC6288289,30564234,CC BY,"Given the high mortality rate (>50%) and potential danger of intrapersonal transmission, highly pathogenic avian influenza (HPAI) H5N1 epidemics still pose a significant threat to humans. γδ T cells, which participate on the front line of the host immune defense, demonstrate both innate, and adaptive characteristics in their immune response and have potent antiviral activity against various viruses. However, the roles of γδ T cells in HPAI H5N1 viral infection remain unclear. In this study, we found that γδ T cells provided a crucial protective function in the defense against HPAI H5N1 viral infection. HPAI H5N1 viruses could directly activate γδ T cells, leading to enhanced CD69 expression and IFN-γ secretion. Importantly, we found that the trimer but not the monomer of HPAI H5N1 virus hemagglutinin (HA) proteins could directly activate γδ T cells. HA-induced γδ T cell activation was dependent on both sialic acid receptors and HA glycosylation, and this activation could be inhibited by the phosphatase calcineurin inhibitor cyclosporin A but not by the phosphatidylinositol 3-kinase (PI3-K) inhibitors wortmannin and LY294002. Our findings provide a further understanding the mechanism underlying γδ T cell-mediated innate and adoptive immune responses against HPAI H5N1 viral infection, which helps to develop novel therapeutic strategies for the treatment of H5N1 infection in the future.",2018 Dec 4,"['Dong, Peng', 'Ju, Xiangwu', 'Yan, Yiwu', 'Zhang, Siya', 'Cai, Menghua', 'Wang, Huaishan', 'Chen, Hui', 'Hu, Yu', 'Cui, Lianxian', 'Zhang, Jianmin', 'He, Wei']",Front Immunol,,,True
72654d4dd1cc47dbe3cfa4988677b5aebb8b88f3,PMC,"Conurbation, Urban, and Rural Living as Determinants of Allergies and Infectious Diseases: Royal College of General Practitioners Research and Surveillance Centre Annual Report 2016-2017",http://dx.doi.org/10.2196/11354,PMC6288591,30478022,CC BY,"BACKGROUND: Living in a conurbation, urban, or rural environment is an important determinant of health. For example, conurbation and rural living is associated with increased respiratory and allergic conditions, whereas a farm or rural upbringing has been shown to be a protective factor against this. OBJECTIVE: The objective of the study was to assess differences in general practice presentations of allergic and infectious disease in those exposed to conurbation or urban living compared with rural environments. METHODS: The population was a nationally representative sample of 175 English general practices covering a population of over 1.6 million patients registered with sentinel network general practices. General practice presentation rates per 100,000 population were reported for allergic rhinitis, asthma, and infectious conditions grouped into upper and lower respiratory tract infections, urinary tract infection, and acute gastroenteritis by the UK Office for National Statistics urban-rural category. We used multivariate logistic regression adjusting for age, sex, ethnicity, deprivation, comorbidities, and smoking status, reporting odds ratios (ORs) with 95% CIs. RESULTS: For allergic rhinitis, the OR was 1.13 (95% CI 1.04-1.23; P=.003) for urban and 1.29 (95% CI 1.19-1.41; P<.001) for conurbation compared with rural dwellers. Conurbation living was associated with a lower OR for both asthma (OR 0.70, 95% CI 0.67-0.73; P<.001) and lower respiratory tract infections (OR 0.94, 95% CI 0.90-0.98; P=.005). Compared with rural dwellers, the OR for upper respiratory tract infection was greater in urban (OR 1.06, 95% CI 1.03-1.08; P<.001) but no different in conurbation dwellers (OR 1.00, 95% CI 0.97-1.03; P=.93). Acute gastroenteritis followed the same pattern: the OR was 1.13 (95% CI 1.01-1.25; P=.03) for urban dwellers and 1.04 (95% CI 0.93-1.17; P=.46) for conurbation dwellers. The OR for urinary tract infection was lower for urban dwellers (OR 0.94, 95% CI 0.89-0.99; P=.02) but higher in conurbation dwellers (OR 1.06, 95% CI 1.00-1.13; P=.04). CONCLUSIONS: Those living in conurbations or urban areas were more likely to consult a general practice for allergic rhinitis and upper respiratory tract infection. Both conurbation and rural living were associated with an increased risk of urinary tract infection. Living in rural areas was associated with an increased risk of asthma and lower respiratory tract infections. The data suggest that living environment may affect rates of consultations for certain conditions. Longitudinal analyses of these data would be useful in providing insights into important determinants.",2018 Nov 26,"['de Lusignan, Simon', 'McGee, Christopher', 'Webb, Rebecca', 'Joy, Mark', 'Byford, Rachel', 'Yonova, Ivelina', 'Hriskova, Mariya', 'Matos Ferreira, Filipa', 'Elliot, Alex J', 'Smith, Gillian', 'Rafi, Imran']",JMIR Public Health Surveill,,,False
2793ad025992d1c278fd341fe970d31f45ac479b,PMC,"Conurbation, Urban, and Rural Living as Determinants of Allergies and Infectious Diseases: Royal College of General Practitioners Research and Surveillance Centre Annual Report 2016-2017",http://dx.doi.org/10.2196/11354,PMC6288591,30478022,CC BY,"BACKGROUND: Living in a conurbation, urban, or rural environment is an important determinant of health. For example, conurbation and rural living is associated with increased respiratory and allergic conditions, whereas a farm or rural upbringing has been shown to be a protective factor against this. OBJECTIVE: The objective of the study was to assess differences in general practice presentations of allergic and infectious disease in those exposed to conurbation or urban living compared with rural environments. METHODS: The population was a nationally representative sample of 175 English general practices covering a population of over 1.6 million patients registered with sentinel network general practices. General practice presentation rates per 100,000 population were reported for allergic rhinitis, asthma, and infectious conditions grouped into upper and lower respiratory tract infections, urinary tract infection, and acute gastroenteritis by the UK Office for National Statistics urban-rural category. We used multivariate logistic regression adjusting for age, sex, ethnicity, deprivation, comorbidities, and smoking status, reporting odds ratios (ORs) with 95% CIs. RESULTS: For allergic rhinitis, the OR was 1.13 (95% CI 1.04-1.23; P=.003) for urban and 1.29 (95% CI 1.19-1.41; P<.001) for conurbation compared with rural dwellers. Conurbation living was associated with a lower OR for both asthma (OR 0.70, 95% CI 0.67-0.73; P<.001) and lower respiratory tract infections (OR 0.94, 95% CI 0.90-0.98; P=.005). Compared with rural dwellers, the OR for upper respiratory tract infection was greater in urban (OR 1.06, 95% CI 1.03-1.08; P<.001) but no different in conurbation dwellers (OR 1.00, 95% CI 0.97-1.03; P=.93). Acute gastroenteritis followed the same pattern: the OR was 1.13 (95% CI 1.01-1.25; P=.03) for urban dwellers and 1.04 (95% CI 0.93-1.17; P=.46) for conurbation dwellers. The OR for urinary tract infection was lower for urban dwellers (OR 0.94, 95% CI 0.89-0.99; P=.02) but higher in conurbation dwellers (OR 1.06, 95% CI 1.00-1.13; P=.04). CONCLUSIONS: Those living in conurbations or urban areas were more likely to consult a general practice for allergic rhinitis and upper respiratory tract infection. Both conurbation and rural living were associated with an increased risk of urinary tract infection. Living in rural areas was associated with an increased risk of asthma and lower respiratory tract infections. The data suggest that living environment may affect rates of consultations for certain conditions. Longitudinal analyses of these data would be useful in providing insights into important determinants.",2018 Nov 26,"['de Lusignan, Simon', 'McGee, Christopher', 'Webb, Rebecca', 'Joy, Mark', 'Byford, Rachel', 'Yonova, Ivelina', 'Hriskova, Mariya', 'Matos Ferreira, Filipa', 'Elliot, Alex J', 'Smith, Gillian', 'Rafi, Imran']",JMIR Public Health Surveill,,,False
3d66a8d4e63b233299a2aba2e3ba08b32657d4a1,PMC,"Conurbation, Urban, and Rural Living as Determinants of Allergies and Infectious Diseases: Royal College of General Practitioners Research and Surveillance Centre Annual Report 2016-2017",http://dx.doi.org/10.2196/11354,PMC6288591,30478022,CC BY,"BACKGROUND: Living in a conurbation, urban, or rural environment is an important determinant of health. For example, conurbation and rural living is associated with increased respiratory and allergic conditions, whereas a farm or rural upbringing has been shown to be a protective factor against this. OBJECTIVE: The objective of the study was to assess differences in general practice presentations of allergic and infectious disease in those exposed to conurbation or urban living compared with rural environments. METHODS: The population was a nationally representative sample of 175 English general practices covering a population of over 1.6 million patients registered with sentinel network general practices. General practice presentation rates per 100,000 population were reported for allergic rhinitis, asthma, and infectious conditions grouped into upper and lower respiratory tract infections, urinary tract infection, and acute gastroenteritis by the UK Office for National Statistics urban-rural category. We used multivariate logistic regression adjusting for age, sex, ethnicity, deprivation, comorbidities, and smoking status, reporting odds ratios (ORs) with 95% CIs. RESULTS: For allergic rhinitis, the OR was 1.13 (95% CI 1.04-1.23; P=.003) for urban and 1.29 (95% CI 1.19-1.41; P<.001) for conurbation compared with rural dwellers. Conurbation living was associated with a lower OR for both asthma (OR 0.70, 95% CI 0.67-0.73; P<.001) and lower respiratory tract infections (OR 0.94, 95% CI 0.90-0.98; P=.005). Compared with rural dwellers, the OR for upper respiratory tract infection was greater in urban (OR 1.06, 95% CI 1.03-1.08; P<.001) but no different in conurbation dwellers (OR 1.00, 95% CI 0.97-1.03; P=.93). Acute gastroenteritis followed the same pattern: the OR was 1.13 (95% CI 1.01-1.25; P=.03) for urban dwellers and 1.04 (95% CI 0.93-1.17; P=.46) for conurbation dwellers. The OR for urinary tract infection was lower for urban dwellers (OR 0.94, 95% CI 0.89-0.99; P=.02) but higher in conurbation dwellers (OR 1.06, 95% CI 1.00-1.13; P=.04). CONCLUSIONS: Those living in conurbations or urban areas were more likely to consult a general practice for allergic rhinitis and upper respiratory tract infection. Both conurbation and rural living were associated with an increased risk of urinary tract infection. Living in rural areas was associated with an increased risk of asthma and lower respiratory tract infections. The data suggest that living environment may affect rates of consultations for certain conditions. Longitudinal analyses of these data would be useful in providing insights into important determinants.",2018 Nov 26,"['de Lusignan, Simon', 'McGee, Christopher', 'Webb, Rebecca', 'Joy, Mark', 'Byford, Rachel', 'Yonova, Ivelina', 'Hriskova, Mariya', 'Matos Ferreira, Filipa', 'Elliot, Alex J', 'Smith, Gillian', 'Rafi, Imran']",JMIR Public Health Surveill,,,False
2ee0e4506b815e43e2169e0784972ece2d364d2f,PMC,"Conurbation, Urban, and Rural Living as Determinants of Allergies and Infectious Diseases: Royal College of General Practitioners Research and Surveillance Centre Annual Report 2016-2017",http://dx.doi.org/10.2196/11354,PMC6288591,30478022,CC BY,"BACKGROUND: Living in a conurbation, urban, or rural environment is an important determinant of health. For example, conurbation and rural living is associated with increased respiratory and allergic conditions, whereas a farm or rural upbringing has been shown to be a protective factor against this. OBJECTIVE: The objective of the study was to assess differences in general practice presentations of allergic and infectious disease in those exposed to conurbation or urban living compared with rural environments. METHODS: The population was a nationally representative sample of 175 English general practices covering a population of over 1.6 million patients registered with sentinel network general practices. General practice presentation rates per 100,000 population were reported for allergic rhinitis, asthma, and infectious conditions grouped into upper and lower respiratory tract infections, urinary tract infection, and acute gastroenteritis by the UK Office for National Statistics urban-rural category. We used multivariate logistic regression adjusting for age, sex, ethnicity, deprivation, comorbidities, and smoking status, reporting odds ratios (ORs) with 95% CIs. RESULTS: For allergic rhinitis, the OR was 1.13 (95% CI 1.04-1.23; P=.003) for urban and 1.29 (95% CI 1.19-1.41; P<.001) for conurbation compared with rural dwellers. Conurbation living was associated with a lower OR for both asthma (OR 0.70, 95% CI 0.67-0.73; P<.001) and lower respiratory tract infections (OR 0.94, 95% CI 0.90-0.98; P=.005). Compared with rural dwellers, the OR for upper respiratory tract infection was greater in urban (OR 1.06, 95% CI 1.03-1.08; P<.001) but no different in conurbation dwellers (OR 1.00, 95% CI 0.97-1.03; P=.93). Acute gastroenteritis followed the same pattern: the OR was 1.13 (95% CI 1.01-1.25; P=.03) for urban dwellers and 1.04 (95% CI 0.93-1.17; P=.46) for conurbation dwellers. The OR for urinary tract infection was lower for urban dwellers (OR 0.94, 95% CI 0.89-0.99; P=.02) but higher in conurbation dwellers (OR 1.06, 95% CI 1.00-1.13; P=.04). CONCLUSIONS: Those living in conurbations or urban areas were more likely to consult a general practice for allergic rhinitis and upper respiratory tract infection. Both conurbation and rural living were associated with an increased risk of urinary tract infection. Living in rural areas was associated with an increased risk of asthma and lower respiratory tract infections. The data suggest that living environment may affect rates of consultations for certain conditions. Longitudinal analyses of these data would be useful in providing insights into important determinants.",2018 Nov 26,"['de Lusignan, Simon', 'McGee, Christopher', 'Webb, Rebecca', 'Joy, Mark', 'Byford, Rachel', 'Yonova, Ivelina', 'Hriskova, Mariya', 'Matos Ferreira, Filipa', 'Elliot, Alex J', 'Smith, Gillian', 'Rafi, Imran']",JMIR Public Health Surveill,,,False
8312f3f0b20525b23f371ec985efe9f5e721f437,PMC,Comparative features of infections of two Massachusetts (Mass) infectious bronchitis virus (IBV) variants isolated from Western Canadian layer flocks,http://dx.doi.org/10.1186/s12917-018-1720-9,PMC6288874,30526618,CC BY,"BACKGROUND: Infectious bronchitis virus (IBV) is one of the leading causes of mortality and morbidity in chickens. There are numerous serotypes and variants, which do not confer cross protection resulting in failure of currently used IBV vaccines. Although variant IBV isolates with major genetic differences have been subjected to comparative studies, it is unknown whether minor genetic differences in IBV variants within a serotype are different in terms of pathogenesis and eliciting host responses. Two Massachusetts (Mass) variant IBV isolates recovered from commercial layer flocks in the Western Canadian provinces of Alberta (AB) and Saskatchewan (SK) were compared genetically and evaluated for their pathogenicity, tissue distribution and ability to recruit and replicate in macrophages. RESULTS: Although whole genome sequencing of these two Mass IBV isolates showed low similarity with the M41 vaccinal strain, they had an identical nucleotide sequence at open reading frames (ORFs) 3a, 3b, envelop (E), matrix (M), 5a and 5b. The rest of the ORFs of these 2 IBV isolates showed 99.9% nucleotide similarity. However, upon experimental infection, we found that the IBV isolate originating from AB was different to the one that originated in SK due to higher tracheal lesion scores and lower lung viral replication and lower genome loads in cecal tonsils. Nevertheless, both IBV isolates elicited host responses characterized by significant macrophage recruitment to the respiratory tract and there was evidence that both IBV isolates replicated within tracheal and lung macrophages. CONCLUSIONS: Overall, this study shows that Mass variant IBV isolates, although possessing minor genetic variations, can lead to significant differences in pathogenicity in young chickens. Further studies are required to investigate the pathogenicity of these two Mass variant IBV isolates in laying hens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1720-9) contains supplementary material, which is available to authorized users.",2018 Dec 10,"['Amarasinghe, Aruna', 'De Silva Senapathi, Upasama', 'Abdul-Cader, Mohamed Sarjoon', 'Popowich, Shelly', 'Marshall, Frank', 'Cork, Susan C.', 'van der Meer, Frank', 'Gomis, Susantha', 'Abdul-Careem, Mohamed Faizal']",BMC Vet Res,,,True
fcd821f2f9391938a54442ec69f64e2370597be5,PMC,Rotavirus VP3 targets MAVS for degradation to inhibit type III interferon expression in intestinal epithelial cells,http://dx.doi.org/10.7554/eLife.39494,PMC6289572,30460894,CC BY,"Rotaviruses (RVs), a leading cause of severe diarrhea in young children and many mammalian species, have evolved multiple strategies to counteract the host innate immunity, specifically interferon (IFN) signaling through RV non-structural protein 1 (NSP1). However, whether RV structural components also subvert antiviral response remains under-studied. Here, we found that MAVS, critical for the host RNA sensing pathway upstream of IFN induction, is degraded by the RV RNA methyl- and guanylyl-transferase (VP3) in a host-range-restricted manner. Mechanistically, VP3 localizes to the mitochondria and mediates the phosphorylation of a previously unidentified SPLTSS motif within the MAVS proline-rich region, leading to its proteasomal degradation and blockade of IFN-λ production in RV-infected intestinal epithelial cells. Importantly, VP3 inhibition of MAVS activity contributes to enhanced RV replication and to viral pathogenesis in vivo. Collectively, our findings establish RV VP3 as a viral antagonist of MAVS function in mammals and uncover a novel pathogen-mediated inhibitory mechanism of MAVS signaling.",,"['Ding, Siyuan', 'Zhu, Shu', 'Ren, Lili', 'Feng, Ningguo', 'Song, Yanhua', 'Ge, Xiaomei', 'Li, Bin', 'Flavell, Richard A', 'Greenberg, Harry B']",eLife.; 7:e39494,,,True
ca3ae7aca20eaa088ea6ebc2a21c619f5181f5f4,PMC,Viral-Induced Enhanced Disease Illness,http://dx.doi.org/10.3389/fmicb.2018.02991,PMC6290032,30568643,CC BY,"Understanding immune responses to viral infections is crucial to progress in the quest for effective infection prevention and control. The host immunity involves various mechanisms to combat viral infections. Under certain circumstances, a viral infection or vaccination may result in a subverted immune system, which may lead to an exacerbated illness. Clinical evidence of enhanced illness by preexisting antibodies from vaccination, infection or maternal passive immunity is available for several viruses and is presumptively proposed for other viruses. Multiple mechanisms have been proposed to explain this phenomenon. It has been confirmed that certain infection- and/or vaccine-induced immunity could exacerbate viral infectivity in Fc receptor- or complement bearing cells- mediated mechanisms. Considering that antibody dependent enhancement (ADE) is a major obstacle in vaccine development, there are continues efforts to understand the underlying mechanisms through identification of the epitopes and antibodies responsible for disease enhancement or protection. This review discusses the recent findings on virally induced ADE, and highlights the potential mechanisms leading to this condition.",2018 Dec 5,"['Smatti, Maria K.', 'Al Thani, Asmaa A.', 'Yassine, Hadi M.']",Front Microbiol,,,True
d7101f63979fbbfbce1f7b9b1e6bd51f50adfd02,PMC,A Functionally Different Immune Phenotype in Cattle Is Associated With Higher Mastitis Incidence,http://dx.doi.org/10.3389/fimmu.2018.02884,PMC6291514,30574152,CC BY,"A novel vaccine against bovine viral diarrhea (BVD) induced pathogenic antibody production in 5–10% of BVD-vaccinated cows. Transfer of these antibodies via colostrum caused Bovine neonatal pancytopenia (BNP) in calves, with a lethality rate of 90%. The exact immunological mechanisms behind the onset of BNP are not fully understood to date. To gain further insight into these mechanisms, we analyzed the immune proteome from alloreactive antibody producers (BNP cows) and non-responders. After in vitro stimulation of peripheral blood derived lymphocytes (PBL), we detected distinctly deviant expression levels of several master regulators of immune responses in BNP cells, pointing to a changed immune phenotype with severe dysregulation of immune response in BNP cows. Interestingly, we also found this response pattern in 22% of non-BVD-vaccinated cows, indicating a genetic predisposition of this immune deviant (ID) phenotype in cattle. We additionally analyzed the functional correlation of the ID phenotype with 10 health parameters and 6 diseases in a retrospective study over 38 months. The significantly increased prevalence of mastitis among ID cows emphasizes the clinical relevance of this deviant immune response and its potential impact on the ability to fight infections.",2018 Dec 6,"['Lutterberg, Karina', 'Kleinwort, Kristina J. H.', 'Hobmaier, Bernhard F.', 'Hauck, Stefanie M.', 'Nüske, Stefan', 'Scholz, Armin M.', 'Deeg, Cornelia A.']",Front Immunol,,,True
cd99b86063184108e06b3b9c0595416888623cec,PMC,Combined use of ELISA and Western blot with recombinant N protein is a powerful tool for the immunodiagnosis of avian infectious bronchitis,http://dx.doi.org/10.1186/s12985-018-1096-2,PMC6292099,30541588,CC BY,"BACKGROUND: The avian infectious bronchitis virus (IBV) remains a significant source of loss in the poultry industry and early diagnosis is required to prevent the disease from spreading. This study examined the combined use of an ELISA and Western blot (WB) to detect antibodies against the nucleocapsid protein (N) of IBV. The coding sequence for N was amplified by RT-PCR and expressed in Escherichia coli. A soluble recombinant N protein (rN) of approximately 50 kDa was obtained. A total of 389 sera were tested against the rN in ELISA and the results were compared with those of the commercial IDEXX IBV Ab test. ELISA-rN achieved a 90.34% sensitivity and 90.16% specificity. WB confirmed all false negative sera in ELISA-rN or IDEXX test as truly positive. The current study indicate that the combined use of rN in ELISA and WB is a powerful tool for the immunodiagnosis of avian infectious bronchitis. METHODS: Constructed recombinant pAE/n expression vectors were used to transform E. coli BL21(DE3) Star competent cells (Invitrogen). The rN of infectious bronchitis virus was purified by affinity chromatography using HisTrap HP 1 mL columns pre-packed with pre-charged Ni Sepharose in the ÄKTAprime Automated Liquid Chromatography system (GE Healthcare). A total of 389 serum samples from chickens were used to develop and evaluate the ELISA-rN test. To standardize the indirect ELISA development, serum dilutions (1:100, 1:200 and 1:400) and different concentrations of purified rN antigen (50, 100 and 200 ng/well) were tested. Positive and negative sera for IBV were used as controls. The results were compared with those obtained from a commercial kit. Serum samples scored as negative with the commercial kit but as positive with the ELISA-rN were further analysed by Western blot analyses using the rN protein as an antigen. The results of the ELISA-rN were compared to the commercial kit results using receiver-operating characteristics curves, area under the curve, and confidence intervals with the software GraphPad Prism version 6.0 for Windows (GraphPad Software, USA). RESULTS: The expected cDNA fragment of approximately 1240 bp was successfully amplified by PCR using primers designed to select for the coding region of the N protein. The rN was expressed as a soluble protein to avoid the refolding steps and, after purification a yield of 10 mg/L of rN was obtained. The SDS-PAGE results demonstrated the presence of two distinct bands that had a molecular mass of approximately 45 and 50 KDa. Out of 244 sera that scored positive in the commercial ELISA IDEXX IBV Ab Test, 220 were also positive in the ELISA-rN, yielding an ELISA-rN test sensitivity of 90.16%. Out of 145 sera that scored negative in the IDEXX IBV Ab Test, 131 also scored negative in the ELISA-rN, indicating a specificity of 90.34%. Sera that tested negative in the ELISA-rN and positive in the commercial test also reacted with the rN protein in Western blot. CONCLUSIONS: The association between the ELISA and Western blot techniques developed in this study with a subunit of IBV (rN) were able to detect antibodies that the commercial ELISA did not detect suggesting that the ELISA-rN has greater sensitivity.",2018 Dec 12,"['Finger, Paula Fonseca', 'Pepe, Michele Soares', 'Dummer, Luana Alves', 'Magalhães, Carolina Georg', 'de Castro, Clarissa Caetano', 'de Oliveira Hübner, Silvia', 'Leite, Fábio Pereira Leivas', 'Ritterbusch, Giseli Aparecida', 'Esteves, Paulo Augusto', 'Conceição, Fabricio Rochedo']",Virol J,,,True
d503366d1b18e110431e5dc7cfe250414c60578f,PMC,Contributions of Farm Animals to Immunology,http://dx.doi.org/10.3389/fvets.2018.00307,PMC6292178,30574508,CC BY,"By their very nature, great advances in immunology are usually underpinned by experiments carried out in animal models and inbred lines of mice. Also, their corresponding knock-out or knock-in derivatives have been the most commonly used animal systems in immunological studies. With much credit to their usefulness, laboratory mice will never provide all the answers to fully understand immunological processes. Large animal models offer unique biological and experimental advantages that have been and continue to be of great value to the understanding of biological and immunological processes. From the identification of B cells to the realization that γδ T cells can function as professional antigen presenting cells, farm animals have contributed significantly to a better understanding of immunity.",2018 Dec 6,"['Guzman, Efrain', 'Montoya, Maria']",Front Vet Sci,,,True
50fc9068ff3d31f1caf01c012e7c08b3ea99d985,PMC,Plant-derived chimeric antibodies inhibit the invasion of human fibroblasts by Toxoplasma gondii,http://dx.doi.org/10.7717/peerj.5780,PMC6294049,30581655,CC BY,"The parasite Toxoplasma gondii causes an opportunistic infection, that is, particularly severe in immunocompromised patients, infants, and neonates. Current antiparasitic drugs are teratogenic and cause hypersensitivity-based toxic side effects especially during prolonged treatment. Furthermore, the recent emergence of drug-resistant toxoplasmosis has reduced the therapeutic impact of such drugs. In an effort to develop recombinant antibodies as a therapeutic alternative, a panel of affinity-matured, T. gondii tachyzoite-specific single-chain variable fragment (scFv) antibodies was selected by phage display and bioinformatic analysis. Further affinity optimization was attempted by introducing point mutations at hotspots within light chain complementarity-determining region 2. This strategy yielded four mutated scFv sequences and a parental scFv that were used to produce five mouse–human chimeric IgGs in Nicotiana benthamiana plants, with yields of 33–72 mg/kg of plant tissue. Immunological analysis confirmed the specific binding of these plant-derived antibodies to T. gondii tachyzoites, and in vitro efficacy was demonstrated by their ability to inhibit the invasion of human fibroblasts and impair parasite infectivity. These novel recombinant antibodies could therefore be suitable for the development of plant-derived immunotherapeutic interventions against toxoplasmosis.",2018 Dec 11,"['Lim, Sherene Swee Yin', 'Chua, Kek Heng', 'Nölke, Greta', 'Spiegel, Holger', 'Goh, Wai Leong', 'Chow, Sek Chuen', 'Kee, Boon Pin', 'Fischer, Rainer', 'Schillberg, Stefan', 'Othman, Rofina Yasmin']",PeerJ,,,True
3ae8228b35bada1b3a05067319b5fceff892a18a,PMC,Plant-derived chimeric antibodies inhibit the invasion of human fibroblasts by Toxoplasma gondii,http://dx.doi.org/10.7717/peerj.5780,PMC6294049,30581655,CC BY,"The parasite Toxoplasma gondii causes an opportunistic infection, that is, particularly severe in immunocompromised patients, infants, and neonates. Current antiparasitic drugs are teratogenic and cause hypersensitivity-based toxic side effects especially during prolonged treatment. Furthermore, the recent emergence of drug-resistant toxoplasmosis has reduced the therapeutic impact of such drugs. In an effort to develop recombinant antibodies as a therapeutic alternative, a panel of affinity-matured, T. gondii tachyzoite-specific single-chain variable fragment (scFv) antibodies was selected by phage display and bioinformatic analysis. Further affinity optimization was attempted by introducing point mutations at hotspots within light chain complementarity-determining region 2. This strategy yielded four mutated scFv sequences and a parental scFv that were used to produce five mouse–human chimeric IgGs in Nicotiana benthamiana plants, with yields of 33–72 mg/kg of plant tissue. Immunological analysis confirmed the specific binding of these plant-derived antibodies to T. gondii tachyzoites, and in vitro efficacy was demonstrated by their ability to inhibit the invasion of human fibroblasts and impair parasite infectivity. These novel recombinant antibodies could therefore be suitable for the development of plant-derived immunotherapeutic interventions against toxoplasmosis.",2018 Dec 11,"['Lim, Sherene Swee Yin', 'Chua, Kek Heng', 'Nölke, Greta', 'Spiegel, Holger', 'Goh, Wai Leong', 'Chow, Sek Chuen', 'Kee, Boon Pin', 'Fischer, Rainer', 'Schillberg, Stefan', 'Othman, Rofina Yasmin']",PeerJ,,,False
bfaeecd7b15a7d6d0563cd323c40681e285d70e7,PMC,Site specific target binding controls RNA cleavage efficiency by the Kaposi's sarcoma-associated herpesvirus endonuclease SOX,http://dx.doi.org/10.1093/nar/gky932,PMC6294519,30321376,CC BY,"A number of viruses remodel the cellular gene expression landscape by globally accelerating messenger RNA (mRNA) degradation. Unlike the mammalian basal mRNA decay enzymes, which largely target mRNA from the 5′ and 3′ end, viruses instead use endonucleases that cleave their targets internally. This is hypothesized to more rapidly inactivate mRNA while maintaining selective power, potentially though the use of a targeting motif(s). Yet, how mRNA endonuclease specificity is achieved in mammalian cells remains largely unresolved. Here, we reveal key features underlying the biochemical mechanism of target recognition and cleavage by the SOX endonuclease encoded by Kaposi's sarcoma-associated herpesvirus (KSHV). Using purified KSHV SOX protein, we reconstituted the cleavage reaction in vitro and reveal that SOX displays robust, sequence-specific RNA binding to residues proximal to the cleavage site, which must be presented in a particular structural context. The strength of SOX binding dictates cleavage efficiency, providing an explanation for the breadth of mRNA susceptibility observed in cells. Importantly, we establish that cleavage site specificity does not require additional cellular cofactors, as had been previously proposed. Thus, viral endonucleases may use a combination of RNA sequence and structure to capture a broad set of mRNA targets while still preserving selectivity.",2018 Dec 14,"['Mendez, Aaron S', 'Vogt, Carolin', 'Bohne, Jens', 'Glaunsinger, Britt A']",Nucleic Acids Res,,,True
11f3022ad1def6dfb1b29712112b96739ff3c498,PMC,Development and evaluation of a broadly reactive reverse transcription recombinase polymerase amplification assay for rapid detection of murine norovirus,http://dx.doi.org/10.1186/s12917-018-1736-1,PMC6295035,30547776,CC BY,"BACKGROUND: Murine norovirus (MNV) is recognized as the most prevalent viral pathogen in captive mouse colonies. The rapid detection assay for MNV would be a useful tool for monitoring and preventing MNV infection. A recombinase polymerase amplification (RPA) assay was established in this study to provide a solution for rapid and sensitive detection of MNV. RESULTS: The detection limit of the RT-RPA assay for the detection of MNV was 1 × 10(2) copies of RNA molecules per reaction. The assay was specific since there was no cross-reaction with other common murine viruses. In addition, the broad reactivity of the RT-RPA assay was validated using the synthesized template carrying seven point mutations among several MNV strains. The MNV RT-RPA assay could detect as few as 1 × 10(2) copies of the mutant per reaction, suggesting the assay could be broadly reactive against a large diversity of MNV strains. Forty eight clinical samples including 16 gastric tissue specimens, 16 cecal tissue specimens and 16 fecal specimens were tested for the validation of the new developed RT-RPA assay. The detection results of RT-RPA and RT-qPCR for clinical samples were very similar, except that a gastric tissue sample which was positive by RT-qPCR, with a RNA titer of 27 copies, was negative by RT-RPA. CONCLUSIONS: A broadly reactive RT-RPA assay was successfully established for MNV detection.",2018 Dec 14,"['Ma, Lei', 'Zeng, Fanwen', 'Cong, Feng', 'Huang, Bihong', 'Zhu, Yujun', 'Wu, Miaoli', 'Xu, Fengjiao', 'Yuan, Wen', 'Huang, Ren', 'Guo, Pengju']",BMC Vet Res,,,True
a5fdb40f1b5bddf4ab24efaddedc40d441e3a130,PMC,A retrospective study of factors associated with treatment decision for nontuberculous mycobacterial lung disease in adults without altered systemic immunity,http://dx.doi.org/10.1186/s12879-018-3559-x,PMC6295085,30547753,CC BY,"BACKGROUND: Nontuberculous mycobacteria (NTM) lung diseases are increasingly recognized as chronic opportunistic infections, occurring in individuals with a wide variety of underlying conditions. In the absence of systemic immunodeficiency, decision of NTM lung disease treatment must relies on a careful risk/benefit assessment, given the requirement of long-term administration of multidrug therapies supported by limited evidence. The primary objective was to identify the factors associated with anti-NTM treatment initiation. Clinical and radiological outcome upon treatment were studied. METHODS: This retrospective, single center study (2013–2016, 45 months) addressed the criteria supporting treatment decision among adults with NTM lung disease without systemic immunodeficiency at our institution, with the assigned goal to harmonize the practice. All patients matched the current international definitions of NTM lung disease according to the American Thoracic Society criteria. Factors associated with anti-NTM treatment were investigated by conditional logistic regression. Clinical and radiological outcomes of treated and untreated NTM-disease cases were examined. Mortality rate was assessed. An expert radiologist conducted a blinded computed tomography (CT)-scan review of the treated and untreated patients. RESULTS: Among 51 cases of NTM lung diseases, 25 (49%) received anti-NTM treatment. In univariate analysis, a body mass index (BMI) < 18 kg/m(2) (odds ratio (OR), 4.2 [95% confidence interval (CI) 1.2–15.2]; p = 0.042), hemoptysis (OR, 11.8 [95% CI 1.35–12.9]; p = 0.026), excavation(s) (OR, 4.8 [95% CI 1.4–16.4], p = 0.012), prior anti-NTM treatment (OR, 5.65 [95% CI 1.06–29.9]; p = 0.042), Aspergillus spp. co-infection (OR, 6.3 [95% CI 1.8–22.2]; p = 0.004) were associated with treatment initiation. In multivariate analysis, Aspergillus spp. co-infection was the only independent determinant of treatment initiation (OR, 5.3 [95% CI 1.1–25.4]; p = 0.036). Twenty-one (81%) patients received ≥3 anti-NTM drugs. Median treatment duration and follow-up were 36.3 (interquartile range [IQR], 13.1–64.4) weeks and 17.1 (IQR, 8.7–27.1) months, respectively. Regarding radiological outcome, 85 CT-scans were reviewed, showing similar rates of regression or stabilization in treated and untreated patients. Overall mortality rate was not different in treated and untreated patients. CONCLUSION: The most relevant variable associated with anti-NTM treatment initiation was Aspergillus spp. co-infection. Radiological regression or stabilization of pulmonary lesions was not different between the treated and untreated patients.",2018 Dec 14,"['Provoost, Judith', 'Valour, Florent', 'Gamondes, Delphine', 'Roux, Sandrine', 'Freymond, Nathalie', 'Perrot, Emilie', 'Souquet, Pierre-Jean', 'Kiakouama-Maleka, Lize', 'Chidiac, Christian', 'Lina, Gérard', 'Dumitrescu, Oana', 'Sénéchal, Agathe', 'Ader, Florence']",BMC Infect Dis,,,True
3c5dd991f2d7b334cc56b2715d73af3fcf1cdca4,PMC,Identification and characterization of Coronaviridae genomes from Vietnamese bats and rats based on conserved protein domains,http://dx.doi.org/10.1093/ve/vey035,PMC6295324,30568804,CC BY,"The Coronaviridae family of viruses encompasses a group of pathogens with a zoonotic potential as observed from previous outbreaks of the severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus. Accordingly, it seems important to identify and document the coronaviruses in animal reservoirs, many of which are uncharacterized and potentially missed by more standard diagnostic assays. A combination of sensitive deep sequencing technology and computational algorithms is essential for virus surveillance, especially for characterizing novel- or distantly related virus strains. Here, we explore the use of profile Hidden Markov Model-defined Pfam protein domains (Pfam domains) encoded by new sequences as a Coronaviridae sequence classification tool. The encoded domains are used first in a triage to identify potential Coronaviridae sequences and then processed using a Random Forest method to classify the sequences to the Coronaviridae genus level. The application of this algorithm on Coronaviridae genomes assembled from agnostic deep sequencing data from surveillance of bats and rats in Dong Thap province (Vietnam) identified thirty-four Alphacoronavirus and eleven Betacoronavirus genomes. This collection of bat and rat coronaviruses genomes provided essential information on the local diversity of coronaviruses and substantially expanded the number of coronavirus full genomes available from bat and rats and may facilitate further molecular studies on this group of viruses.",2018 Dec 15,"['Phan, My V T', 'Ngo Tri, Tue', 'Hong Anh, Pham', 'Baker, Stephen', 'Kellam, Paul', 'Cotten, Matthew']",Virus Evol,,,True
213313b5fe57d1ecf1930503ed0e7fd8e1dc73e7,PMC,Detection of porcine epidemic diarrhea virus (PEDV) IgG and IgA in muscle tissue exudate (“meat juice”) specimens,http://dx.doi.org/10.1186/s40813-018-0107-4,PMC6297947,30574353,CC BY,"The diagnostic performance of porcine epidemic diarrhea virus (PEDV) IgG and IgA ELISAs was evaluated using paired serum and meat juice samples collected from PEDV-negative (n = 50) and PEDV-inoculated pigs (n = 87). Serum samples were tested by PEDV (IgG, IgA) ELISAs using a procedure performed routinely at the Iowa State University-Veterinary Diagnostic Laboratory (ISU-VDL). Serum samples were tested using PEDV serum IgG and IgA ELISA procedures as routinely performed at the Iowa State University-Veterinary Diagnostic Laboratory (ISU-VDL). Serum samples were diluted 1:50 and conjugate concentrations were 1/20,000 for IgG and 1/3000 for IgA. Meat juice samples were tested using the serum PEDV IgG and IgA ELISAs, with modifications, i.e., meat juice samples were diluted 1:25 and conjugate concentrations were 1/40,000 for IgG and 1/10,000 for IgA. Receiver operator characteristic (ROC) curve analyses were used to estimate diagnostic sensitivities and specificities over a range of sample-to-positive (S/P) cutoffs. Consistent with previous reports, this study showed that the PEDV IgG and IgA meat juice ELISAs provided excellent diagnostic performance and suggest that meat juice recovered from samples collected at slaughter could be used in routine PEDV surveillance.",2018 Dec 18,"['Poonsuk, Korakrit', 'Cheng, Ting-Yu', 'Ji, Ju', 'Zimmerman, Jeffrey', 'Giménez-Lirola, Luis']",Porcine Health Manag,,,True
db2773bfab2b81fdcf13212b9c7b4fef0af57fcf,PMC,KILchip v1.0: A Novel Plasmodium falciparum Merozoite Protein Microarray to Facilitate Malaria Vaccine Candidate Prioritization,http://dx.doi.org/10.3389/fimmu.2018.02866,PMC6298441,30619257,CC BY,"Passive transfer studies in humans clearly demonstrated the protective role of IgG antibodies against malaria. Identifying the precise parasite antigens that mediate immunity is essential for vaccine design, but has proved difficult. Completion of the Plasmodium falciparum genome revealed thousands of potential vaccine candidates, but a significant bottleneck remains in their validation and prioritization for further evaluation in clinical trials. Focusing initially on the Plasmodium falciparum merozoite proteome, we used peer-reviewed publications, multiple proteomic and bioinformatic approaches, to select and prioritize potential immune targets. We expressed 109 P. falciparum recombinant proteins, the majority of which were obtained using a mammalian expression system that has been shown to produce biologically functional extracellular proteins, and used them to create KILchip v1.0: a novel protein microarray to facilitate high-throughput multiplexed antibody detection from individual samples. The microarray assay was highly specific; antibodies against P. falciparum proteins were detected exclusively in sera from malaria-exposed but not malaria-naïve individuals. The intensity of antibody reactivity varied as expected from strong to weak across well-studied antigens such as AMA1 and RH5 (Kruskal–Wallis H test for trend: p < 0.0001). The inter-assay and intra-assay variability was minimal, with reproducible results obtained in re-assays using the same chip over a duration of 3 months. Antibodies quantified using the multiplexed format in KILchip v1.0 were highly correlated with those measured in the gold-standard monoplex ELISA [median (range) Spearman's R of 0.84 (0.65–0.95)]. KILchip v1.0 is a robust, scalable and adaptable protein microarray that has broad applicability to studies of naturally acquired immunity against malaria by providing a standardized tool for the detection of antibody correlates of protection. It will facilitate rapid high-throughput validation and prioritization of potential Plasmodium falciparum merozoite-stage antigens paving the way for urgently needed clinical trials for the next generation of malaria vaccines.",2018 Dec 11,"['Kamuyu, Gathoni', 'Tuju, James', 'Kimathi, Rinter', 'Mwai, Kennedy', 'Mburu, James', 'Kibinge, Nelson', 'Chong Kwan, Marisa', 'Hawkings, Sam', 'Yaa, Reuben', 'Chepsat, Emily', 'Njunge, James M.', 'Chege, Timothy', 'Guleid, Fatuma', 'Rosenkranz, Micha', 'Kariuki, Christopher K.', 'Frank, Roland', 'Kinyanjui, Samson M.', 'Murungi, Linda M.', 'Bejon, Philip', 'Färnert, Anna', 'Tetteh, Kevin K. A.', 'Beeson, James G.', 'Conway, David J.', 'Marsh, Kevin', 'Rayner, Julian C.', 'Osier, Faith H. A.']",Front Immunol,,,True
f3c309c596c20f48f493b77e714ce957d877bdcb,PMC,Rotavirus A in wild and domestic animals from areas with environmental degradation in the Brazilian Amazon,http://dx.doi.org/10.1371/journal.pone.0209005,PMC6298726,30562373,CC BY,"Acute gastroenteritis is one of the main causes of mortality in humans and young animals. Domestic and mainly wild animals such as bats, small rodents and birds are highly diversified animals in relation to their habitats and ecological niches and are widely distributed geographically in environments of forest fragmentation in some areas of the Amazon, being considered important sources for viruses that affect humans and other animals. Due to the anthropical activities, these animals changed their natural habitat and adapted to urbanized environments, thus representing risks to human and animal health. Although the knowledge of the global diversity of enteric viruses is scarce, there are reports demonstrating the detection of rotavirus in domestic animals and animals of productive systems, such as bovines and pigs. The present study investigated the prevalence of Rotavirus A in 648 fecal samples of different animal species from the northeastern mesoregion of the state of Pará, Brazil, which is characterized as an urbanized area with forest fragments. The fecal specimens were collected from October 2014 to April 2016 and subjected to a Qualitative Real-Time Polymerase Chain Reaction (RT-qPCR), using the NSP3 gene as a target. It was observed that 27.5% (178/648) of the samples presented positive results for RVA, with 178 samples distributed in birds (23.6%), canines (21.35%), chiropterans (17.98%), bovines (14.6%), horses (8.43%), small rodents (6.74%), pigs (3.93%) and felines (3.37%), demonstrating the circulation of RVA in domestic animals and suggesting that such proximity could cause transmissions between different species and the occurrence of rearrangements in the genome of RVA as already described in the literature, associated to the traces of environmental degradation in the studied areas.",2018 Dec 18,"['de Barros, Bruno de Cássio Veloso', 'Chagas, Elaine Nunes', 'Bezerra, Luna Wanessa', 'Ribeiro, Laila Graziela', 'Duarte Júnior, Jose Wandilson Barboza', 'Pereira, Diego', 'da Penha Junior, Edvaldo Tavares', 'Silva, Julia Rezende', 'Bezerra, Delana Andreza Melo', 'Bandeira, Renato Silva', 'Pinheiro, Helder Henrique Costa', 'Guerra, Sylvia de Fátima dos Santos', 'Guimarães, Ricardo José de Paula Souza e', ""Mascarenhas, Joana D'Arc Pereira""]",PLoS One,,,True
04a02b2f24ba9cf14a860a98b25f65ef2afd73fd,PMC,Inference and control of the nosocomial transmission of methicillin-resistant Staphylococcus aureus,http://dx.doi.org/10.7554/eLife.40977,PMC6298769,30560786,CC BY,"Methicillin-resistant Staphylococcus aureus (MRSA) is a continued threat to human health in both community and healthcare settings. In hospitals, control efforts would benefit from accurate estimation of asymptomatic colonization and infection importation rates from the community. However, developing such estimates remains challenging due to limited observation of colonization and complicated transmission dynamics within hospitals and the community. Here, we develop an inference framework that can estimate these key quantities by combining statistical filtering techniques, an agent-based model, and real-world patient-to-patient contact networks, and use this framework to infer nosocomial transmission and infection importation over an outbreak spanning 6 years in 66 Swedish hospitals. In particular, we identify a small number of patients with disproportionately high risk of colonization. In retrospective control experiments, interventions targeted to these individuals yield a substantial improvement over heuristic strategies informed by number of contacts, length of stay and contact tracing.",,"['Pei, Sen', 'Morone, Flaviano', 'Liljeros, Fredrik', 'Makse, Hernán', 'Shaman, Jeffrey L']",eLife.; 7:e40977,,,True
e6c10d7b9b6a71574918af6a89617962c6bbcf3d,PMC,Respiratory Viral Infections in Patients With Cancer or Undergoing Hematopoietic Cell Transplant,http://dx.doi.org/10.3389/fmicb.2018.03097,PMC6299032,30619176,CC BY,"Survival rates for pediatric cancer have steadily improved over time but it remains a significant cause of morbidity and mortality among children. Infections are a major complication of cancer and its treatment. Community acquired respiratory viral infections (CRV) in these patients increase morbidity, mortality and can lead to delay in chemotherapy. These are the result of infections with a heterogeneous group of viruses including RNA viruses, such as respiratory syncytial virus (RSV), influenza virus (IV), parainfluenza virus (PIV), metapneumovirus (HMPV), rhinovirus (RhV), and coronavirus (CoV). These infections maintain a similar seasonal pattern to those of immunocompetent patients. Clinical manifestations vary significantly depending on the type of virus and the type and degree of immunosuppression, ranging from asymptomatic or mild disease to rapidly progressive fatal pneumonia Infections in this population are characterized by a high rate of progression from upper to lower respiratory tract infection and prolonged viral shedding. Use of corticosteroids and immunosuppressive therapy are risk factors for severe disease. The clinical course is often difficult to predict, and clinical signs are unreliable. Accurate prognostic viral and immune markers, which have become part of the standard of care for systemic viral infections, are currently lacking; and management of CRV infections remains controversial. Defining effective prophylactic and therapeutic strategies is challenging, especially considering, the spectrum of immunocompromised patients, the variety of respiratory viruses, and the presence of other opportunistic infections and medical problems. Prevention remains one of the most important strategies against these viruses. Early diagnosis, supportive care and antivirals at an early stage, when available and indicated, have proven beneficial. However, with the exception of neuraminidase inhibitors for influenza infection, there are no accepted treatments. In high-risk patients, pre-emptive treatment with antivirals for upper respiratory tract infection (URTI) to decrease progression to LRTI is a common strategy. In the future, viral load and immune markers may prove beneficial in predicting severe disease, supporting decision making and monitor treatment in this population.",2018 Dec 12,"['Hijano, Diego R.', 'Maron, Gabriela', 'Hayden, Randall T.']",Front Microbiol,,,True
f0c2cd2793d71f1ea11a810442a2c06d5013e899,PMC,Clara Cell 10 kDa Protein Alleviates Murine Hepatitis Virus Strain 3-Induced Fulminant Hepatitis by Inhibiting Fibrinogen-Like Protein 2 Expression,http://dx.doi.org/10.3389/fimmu.2018.02935,PMC6300492,30619295,CC BY,"Background: Fulminant hepatitis (FH) is a serious threat to human life, accompanied by massive and rapid necroinflammation. Kupffer cells, the major immune cell population involved in innate immune responses, are considered to be central for FH. Fibrinogen-like protein 2 (Fgl2) is a pro-coagulant protein that is substantially induced in macrophages upon viral infection, and Fgl2 depletion represses murine hepatitis virus strain 3 (MHV-3) infection. Clara cell 10 kDa (CC10) protein is a secretory protein with anti-inflammatory properties in allergic rhinitis and asthma. However, its mechanisms of action and pathogenic roles in other disease are still unclear. In this study, we aimed to determine the role of CC10 in FH and the regulation of Fgl2 by CC10. Methods: A mouse FH model was established by peritoneal injection of MHV-3. The mice received CC10 protein through tail vein injection before viral infection. Survival rate, liver function, liver histology, fibrin deposition, and necrosis were examined. The regulatory effect of CC10 on Fgl2 expression was investigated using THP-1 cells and mouse peritoneal macrophages in vitro. Results: In the mouse FH model induced by MHV-3, the survival rate increased from 0 to 12.5% in the CC10 group compared to that in the saline-only control group. Meanwhile, the levels of ALT and AST in serum were significantly decreased and liver damage was reduced. Furthermore, hepatic Fgl2, TNF-α, and IL-1β expression was obviously downregulated together with fibrin deposition, and hepatocyte apoptosis was reduced after administration of CC10 protein. In vitro, CC10 was found to significantly inhibit the expression of Fgl2 in IFN-γ-treated THP-1 cells and MHV-3-infected mouse peritoneal macrophages by western blot and real-time PCR. However, there was no direct interaction between CC10 and Fgl2 as shown by co-immunoprecipitation. Microarray investigations suggested that HMG-box transcription factor 1 (HBP1) was significantly low in CC10-treated and IFN-γ-primed THP-1 cells. HBP1-siRNA treatment abrogated the inhibitory effect of CC10 on Fgl2 expression in Human Umbilical Vein Endothelial cells (HUVECs). Conclusion:CC10 protects against MHV-3-induced FH via suppression of Fgl2 expression in macrophages. Such effects may be mediated by the transcription factor HBP1.",2018 Dec 13,"['Yu, Haijing', 'Liu, Yang', 'Wang, Hongwu', 'Wan, Xiaoyang', 'Huang, Jiaquan', 'Yan, Weiming', 'Xi, Dong', 'Luo, Xiaoping', 'Shen, Guanxin', 'Ning, Qin']",Front Immunol,,,True
ced27e69659f1c568659e95f8f7ce66a75144d64,PMC,Structure of the type VI secretion system TssK–TssF–TssG baseplate subcomplex revealed by cryo-electron microscopy,http://dx.doi.org/10.1038/s41467-018-07796-5,PMC6300606,30568167,CC BY,"Type VI secretion systems (T6SSs) translocate effectors into target cells and are made of a contractile sheath and a tube docked onto a multi-protein transmembrane complex via a baseplate. Although some information is available about the mechanisms of tail contraction leading to effector delivery, the detailed architecture and function of the baseplate remain unknown. Here, we report the 3.7 Å resolution cryo-electron microscopy reconstruction of an enteroaggregative Escherichia coli baseplate subcomplex assembled from TssK, TssF and TssG. The structure reveals two TssK trimers interact with a locally pseudo-3-fold symmetrical complex comprising two copies of TssF and one copy of TssG. TssF and TssG are structurally related to each other and to components of the phage T4 baseplate and of the type IV secretion system, strengthening the evolutionary relationships among these macromolecular machines. These results, together with bacterial two-hybrid assays, provide a structural framework to understand the T6SS baseplate architecture.",2018 Dec 19,"['Park, Young-Jun', 'Lacourse, Kaitlyn D.', 'Cambillau, Christian', 'DiMaio, Frank', 'Mougous, Joseph D.', 'Veesler, David']",Nat Commun,,,False
8fabc2a9e166b723e115f9ae5e16bf6121782ac6,PMC,Structure of the type VI secretion system TssK–TssF–TssG baseplate subcomplex revealed by cryo-electron microscopy,http://dx.doi.org/10.1038/s41467-018-07796-5,PMC6300606,30568167,CC BY,"Type VI secretion systems (T6SSs) translocate effectors into target cells and are made of a contractile sheath and a tube docked onto a multi-protein transmembrane complex via a baseplate. Although some information is available about the mechanisms of tail contraction leading to effector delivery, the detailed architecture and function of the baseplate remain unknown. Here, we report the 3.7 Å resolution cryo-electron microscopy reconstruction of an enteroaggregative Escherichia coli baseplate subcomplex assembled from TssK, TssF and TssG. The structure reveals two TssK trimers interact with a locally pseudo-3-fold symmetrical complex comprising two copies of TssF and one copy of TssG. TssF and TssG are structurally related to each other and to components of the phage T4 baseplate and of the type IV secretion system, strengthening the evolutionary relationships among these macromolecular machines. These results, together with bacterial two-hybrid assays, provide a structural framework to understand the T6SS baseplate architecture.",2018 Dec 19,"['Park, Young-Jun', 'Lacourse, Kaitlyn D.', 'Cambillau, Christian', 'DiMaio, Frank', 'Mougous, Joseph D.', 'Veesler, David']",Nat Commun,,,False
555c6d5dec99b8cf5c8c97415b127dbe30179721,PMC,Structure of the type VI secretion system TssK–TssF–TssG baseplate subcomplex revealed by cryo-electron microscopy,http://dx.doi.org/10.1038/s41467-018-07796-5,PMC6300606,30568167,CC BY,"Type VI secretion systems (T6SSs) translocate effectors into target cells and are made of a contractile sheath and a tube docked onto a multi-protein transmembrane complex via a baseplate. Although some information is available about the mechanisms of tail contraction leading to effector delivery, the detailed architecture and function of the baseplate remain unknown. Here, we report the 3.7 Å resolution cryo-electron microscopy reconstruction of an enteroaggregative Escherichia coli baseplate subcomplex assembled from TssK, TssF and TssG. The structure reveals two TssK trimers interact with a locally pseudo-3-fold symmetrical complex comprising two copies of TssF and one copy of TssG. TssF and TssG are structurally related to each other and to components of the phage T4 baseplate and of the type IV secretion system, strengthening the evolutionary relationships among these macromolecular machines. These results, together with bacterial two-hybrid assays, provide a structural framework to understand the T6SS baseplate architecture.",2018 Dec 19,"['Park, Young-Jun', 'Lacourse, Kaitlyn D.', 'Cambillau, Christian', 'DiMaio, Frank', 'Mougous, Joseph D.', 'Veesler, David']",Nat Commun,,,True
8a73c5ca616cd3522175d04a8644412b207f3d67,PMC,Atg5 Supports Rickettsia australis Infection in Macrophages In Vitro and In Vivo,http://dx.doi.org/10.1128/IAI.00651-18,PMC6300621,30297526,CC BY,"Rickettsiae can cause life-threatening infections in humans. Macrophages are one of the initial targets for rickettsiae after inoculation by ticks. However, it remains poorly understood how rickettsiae remain free in macrophages prior to establishing their infection in microvascular endothelial cells. Here, we demonstrated that the concentration of Rickettsia australis was significantly greater in infected tissues of Atg5(flox/flox) mice than in the counterparts of Atg5(flox/flox) Lyz-Cre mice, in association with a reduced level of interleukin-1β (IL-1β) in serum. The greater concentration of R. australis in Atg5(flox/flox) bone marrow-derived macrophages (BMMs) than in Atg5(flox/flox) Lyz-Cre BMMs in vitro was abolished by exogenous treatment with recombinant IL-1β. Rickettsia australis induced significantly increased levels of light chain 3 (LC3) form II (LC3-II) and LC3 puncta in Atg5-competent BMMs but not in Atg5-deficient BMMs, while no p62 turnover was observed. Further analysis found the colocalization of LC3 with a small portion of R. australis and Rickettsia-containing double-membrane-bound vacuoles in the BMMs of B6 mice. Moreover, treatment with rapamycin significantly increased the concentrations of R. australis in B6 BMMs compared to those in the untreated B6 BMM controls. Taken together, our results demonstrate that Atg5 favors R. australis infection in mouse macrophages in association with a suppressed level of IL-1β production but not active autophagy flux. These data highlight the contribution of Atg5 in macrophages to the pathogenesis of rickettsial diseases.",2018 Dec 19,"['Bechelli, Jeremy', 'Vergara, Leoncio', 'Smalley, Claire', 'Buzhdygan, Tetyana P.', 'Bender, Sean', 'Zhang, William', 'Liu, Yan', 'Popov, Vsevolod L.', 'Wang, Jin', 'Garg, Nisha', 'Hwang, Seungmin', 'Walker, David H.', 'Fang, Rong']",Infect Immun,,,False
c9c34b0ef9eacdf1bce00a71e1ff612479c3f004,PMC,Atg5 Supports Rickettsia australis Infection in Macrophages In Vitro and In Vivo,http://dx.doi.org/10.1128/IAI.00651-18,PMC6300621,30297526,CC BY,"Rickettsiae can cause life-threatening infections in humans. Macrophages are one of the initial targets for rickettsiae after inoculation by ticks. However, it remains poorly understood how rickettsiae remain free in macrophages prior to establishing their infection in microvascular endothelial cells. Here, we demonstrated that the concentration of Rickettsia australis was significantly greater in infected tissues of Atg5(flox/flox) mice than in the counterparts of Atg5(flox/flox) Lyz-Cre mice, in association with a reduced level of interleukin-1β (IL-1β) in serum. The greater concentration of R. australis in Atg5(flox/flox) bone marrow-derived macrophages (BMMs) than in Atg5(flox/flox) Lyz-Cre BMMs in vitro was abolished by exogenous treatment with recombinant IL-1β. Rickettsia australis induced significantly increased levels of light chain 3 (LC3) form II (LC3-II) and LC3 puncta in Atg5-competent BMMs but not in Atg5-deficient BMMs, while no p62 turnover was observed. Further analysis found the colocalization of LC3 with a small portion of R. australis and Rickettsia-containing double-membrane-bound vacuoles in the BMMs of B6 mice. Moreover, treatment with rapamycin significantly increased the concentrations of R. australis in B6 BMMs compared to those in the untreated B6 BMM controls. Taken together, our results demonstrate that Atg5 favors R. australis infection in mouse macrophages in association with a suppressed level of IL-1β production but not active autophagy flux. These data highlight the contribution of Atg5 in macrophages to the pathogenesis of rickettsial diseases.",2018 Dec 19,"['Bechelli, Jeremy', 'Vergara, Leoncio', 'Smalley, Claire', 'Buzhdygan, Tetyana P.', 'Bender, Sean', 'Zhang, William', 'Liu, Yan', 'Popov, Vsevolod L.', 'Wang, Jin', 'Garg, Nisha', 'Hwang, Seungmin', 'Walker, David H.', 'Fang, Rong']",Infect Immun,,,True
c1f0aaec8b7529fdf5fc1db7fdf3791300bacb18,PMC,Toll-like receptor 4 in acute viral infection: Too much of a good thing,http://dx.doi.org/10.1371/journal.ppat.1007390,PMC6301565,30571771,CC BY,,2018 Dec 20,"['Olejnik, Judith', 'Hume, Adam J.', 'Mühlberger, Elke']",PLoS Pathog,,,True
6cfa11e4308af9ef83f7800b45f011139915cd43,PMC,"GI-16 lineage (624/I or Q1), there and back again: The history of one of the major threats for poultry farming of our era",http://dx.doi.org/10.1371/journal.pone.0203513,PMC6301571,30571679,CC BY,"The genetic variability of Infectious bronchitis virus (IBV) is one of the main challenges for its control, hindering not only the development of effective vaccination strategies but also its classification and, consequently, epidemiology understanding. The 624/I and Q1 genotypes, now recognized to be part of the GI-16 lineage, represent an excellent example of the practical consequences of IBV molecular epidemiology limited knowledge. In fact, being their common origin unrecognized for a long time, independent epidemiological pictures were drawn for the two genotypes. To fix this misinterpretation, the present study reconstructs the history, population dynamics and spreading patterns of GI-16 lineage as a whole using a phylodynamic approach. A collection of worldwide available hypervariable region 1 and 2 (HVR12) and 3 (HVR3) sequences of the S1 protein was analysed together with 258 HVR3 sequences obtained from samples collected in Italy (the country where this genotype was initially identified) since 1963. The results demonstrate that after its emergence at the beginning of the XX century, GI-16 was able to persist until present days in Italy. Approximately in the late 1980s, it migrated to Asia, which became the main nucleus for further spreading to Middle East, Europe and especially South America, likely through multiple introduction events. A remarkable among-country diffusion was also demonstrated in Asia and South America. Interestingly, although most of the recent Italian GI-16 strains originated from ancestral viruses detected in the same country, a couple were closely related to Chinese ones, supporting a backward viral flow from China to Italy. Besides to the specific case-study results, this work highlights the misconceptions that originate from the lack of a unified nomenclature and poor molecular epidemiology data generation and sharing. This shortcoming appears particularly relevant since the described scenario could likely be shared by many other IBV genotypes and pathogens in general.",2018 Dec 20,"['Franzo, Giovanni', 'Cecchinato, Mattia', 'Tosi, Giovanni', 'Fiorentini, Laura', 'Faccin, Francesca', 'Tucciarone, Claudia Maria', 'Trogu, Tiziana', 'Barbieri, Ilaria', 'Massi, Paola', 'Moreno, Ana']",PLoS One,,,True
b2d6afd66e3ea609ea7ad36c8ec2ee8d151a99c3,PMC,"GI-16 lineage (624/I or Q1), there and back again: The history of one of the major threats for poultry farming of our era",http://dx.doi.org/10.1371/journal.pone.0203513,PMC6301571,30571679,CC BY,"The genetic variability of Infectious bronchitis virus (IBV) is one of the main challenges for its control, hindering not only the development of effective vaccination strategies but also its classification and, consequently, epidemiology understanding. The 624/I and Q1 genotypes, now recognized to be part of the GI-16 lineage, represent an excellent example of the practical consequences of IBV molecular epidemiology limited knowledge. In fact, being their common origin unrecognized for a long time, independent epidemiological pictures were drawn for the two genotypes. To fix this misinterpretation, the present study reconstructs the history, population dynamics and spreading patterns of GI-16 lineage as a whole using a phylodynamic approach. A collection of worldwide available hypervariable region 1 and 2 (HVR12) and 3 (HVR3) sequences of the S1 protein was analysed together with 258 HVR3 sequences obtained from samples collected in Italy (the country where this genotype was initially identified) since 1963. The results demonstrate that after its emergence at the beginning of the XX century, GI-16 was able to persist until present days in Italy. Approximately in the late 1980s, it migrated to Asia, which became the main nucleus for further spreading to Middle East, Europe and especially South America, likely through multiple introduction events. A remarkable among-country diffusion was also demonstrated in Asia and South America. Interestingly, although most of the recent Italian GI-16 strains originated from ancestral viruses detected in the same country, a couple were closely related to Chinese ones, supporting a backward viral flow from China to Italy. Besides to the specific case-study results, this work highlights the misconceptions that originate from the lack of a unified nomenclature and poor molecular epidemiology data generation and sharing. This shortcoming appears particularly relevant since the described scenario could likely be shared by many other IBV genotypes and pathogens in general.",2018 Dec 20,"['Franzo, Giovanni', 'Cecchinato, Mattia', 'Tosi, Giovanni', 'Fiorentini, Laura', 'Faccin, Francesca', 'Tucciarone, Claudia Maria', 'Trogu, Tiziana', 'Barbieri, Ilaria', 'Massi, Paola', 'Moreno, Ana']",PLoS One,,,False
f6f37ba5a2dd88775b18db2b63ea9d1b5dabe8ec,PMC,"GI-16 lineage (624/I or Q1), there and back again: The history of one of the major threats for poultry farming of our era",http://dx.doi.org/10.1371/journal.pone.0203513,PMC6301571,30571679,CC BY,"The genetic variability of Infectious bronchitis virus (IBV) is one of the main challenges for its control, hindering not only the development of effective vaccination strategies but also its classification and, consequently, epidemiology understanding. The 624/I and Q1 genotypes, now recognized to be part of the GI-16 lineage, represent an excellent example of the practical consequences of IBV molecular epidemiology limited knowledge. In fact, being their common origin unrecognized for a long time, independent epidemiological pictures were drawn for the two genotypes. To fix this misinterpretation, the present study reconstructs the history, population dynamics and spreading patterns of GI-16 lineage as a whole using a phylodynamic approach. A collection of worldwide available hypervariable region 1 and 2 (HVR12) and 3 (HVR3) sequences of the S1 protein was analysed together with 258 HVR3 sequences obtained from samples collected in Italy (the country where this genotype was initially identified) since 1963. The results demonstrate that after its emergence at the beginning of the XX century, GI-16 was able to persist until present days in Italy. Approximately in the late 1980s, it migrated to Asia, which became the main nucleus for further spreading to Middle East, Europe and especially South America, likely through multiple introduction events. A remarkable among-country diffusion was also demonstrated in Asia and South America. Interestingly, although most of the recent Italian GI-16 strains originated from ancestral viruses detected in the same country, a couple were closely related to Chinese ones, supporting a backward viral flow from China to Italy. Besides to the specific case-study results, this work highlights the misconceptions that originate from the lack of a unified nomenclature and poor molecular epidemiology data generation and sharing. This shortcoming appears particularly relevant since the described scenario could likely be shared by many other IBV genotypes and pathogens in general.",2018 Dec 20,"['Franzo, Giovanni', 'Cecchinato, Mattia', 'Tosi, Giovanni', 'Fiorentini, Laura', 'Faccin, Francesca', 'Tucciarone, Claudia Maria', 'Trogu, Tiziana', 'Barbieri, Ilaria', 'Massi, Paola', 'Moreno, Ana']",PLoS One,,,False
6c0a5a7d7415c99ef7c7dea7da180c86ffcad3e6,PMC,"GI-16 lineage (624/I or Q1), there and back again: The history of one of the major threats for poultry farming of our era",http://dx.doi.org/10.1371/journal.pone.0203513,PMC6301571,30571679,CC BY,"The genetic variability of Infectious bronchitis virus (IBV) is one of the main challenges for its control, hindering not only the development of effective vaccination strategies but also its classification and, consequently, epidemiology understanding. The 624/I and Q1 genotypes, now recognized to be part of the GI-16 lineage, represent an excellent example of the practical consequences of IBV molecular epidemiology limited knowledge. In fact, being their common origin unrecognized for a long time, independent epidemiological pictures were drawn for the two genotypes. To fix this misinterpretation, the present study reconstructs the history, population dynamics and spreading patterns of GI-16 lineage as a whole using a phylodynamic approach. A collection of worldwide available hypervariable region 1 and 2 (HVR12) and 3 (HVR3) sequences of the S1 protein was analysed together with 258 HVR3 sequences obtained from samples collected in Italy (the country where this genotype was initially identified) since 1963. The results demonstrate that after its emergence at the beginning of the XX century, GI-16 was able to persist until present days in Italy. Approximately in the late 1980s, it migrated to Asia, which became the main nucleus for further spreading to Middle East, Europe and especially South America, likely through multiple introduction events. A remarkable among-country diffusion was also demonstrated in Asia and South America. Interestingly, although most of the recent Italian GI-16 strains originated from ancestral viruses detected in the same country, a couple were closely related to Chinese ones, supporting a backward viral flow from China to Italy. Besides to the specific case-study results, this work highlights the misconceptions that originate from the lack of a unified nomenclature and poor molecular epidemiology data generation and sharing. This shortcoming appears particularly relevant since the described scenario could likely be shared by many other IBV genotypes and pathogens in general.",2018 Dec 20,"['Franzo, Giovanni', 'Cecchinato, Mattia', 'Tosi, Giovanni', 'Fiorentini, Laura', 'Faccin, Francesca', 'Tucciarone, Claudia Maria', 'Trogu, Tiziana', 'Barbieri, Ilaria', 'Massi, Paola', 'Moreno, Ana']",PLoS One,,,False
d18236f2eef84aa028d5745f66aa1b42aad7d44b,PMC,Predicting wildlife reservoirs and global vulnerability to zoonotic Flaviviruses,http://dx.doi.org/10.1038/s41467-018-07896-2,PMC6303316,30575757,CC BY,Flaviviruses continue to cause globally relevant epidemics and have emerged or re-emerged in regions that were previously unaffected. Factors determining emergence of flaviviruses and continuing circulation in sylvatic cycles are incompletely understood. Here we identify potential sylvatic reservoirs of flaviviruses and characterize the macro-ecological traits common to known wildlife hosts to predict the risk of sylvatic flavivirus transmission among wildlife and identify regions that could be vulnerable to outbreaks. We evaluate variability in wildlife hosts for zoonotic flaviviruses and find that flaviviruses group together in distinct clusters with similar hosts. Models incorporating ecological and climatic variables as well as life history traits shared by flaviviruses predict new host species with similar host characteristics. The combination of vector distribution data with models for flavivirus hosts allows for prediction of  global vulnerability to flaviviruses and provides potential targets for disease surveillance in animals and humans.,2018 Dec 21,"['Pandit, Pranav S.', 'Doyle, Megan M.', 'Smart, Katrina M.', 'Young, Cristin C. W.', 'Drape, Gaylen W.', 'Johnson, Christine K.']",Nat Commun,,,False
dd64529786dd62a83e7d182e539fb2f3aaaae25f,PMC,Predicting wildlife reservoirs and global vulnerability to zoonotic Flaviviruses,http://dx.doi.org/10.1038/s41467-018-07896-2,PMC6303316,30575757,CC BY,Flaviviruses continue to cause globally relevant epidemics and have emerged or re-emerged in regions that were previously unaffected. Factors determining emergence of flaviviruses and continuing circulation in sylvatic cycles are incompletely understood. Here we identify potential sylvatic reservoirs of flaviviruses and characterize the macro-ecological traits common to known wildlife hosts to predict the risk of sylvatic flavivirus transmission among wildlife and identify regions that could be vulnerable to outbreaks. We evaluate variability in wildlife hosts for zoonotic flaviviruses and find that flaviviruses group together in distinct clusters with similar hosts. Models incorporating ecological and climatic variables as well as life history traits shared by flaviviruses predict new host species with similar host characteristics. The combination of vector distribution data with models for flavivirus hosts allows for prediction of  global vulnerability to flaviviruses and provides potential targets for disease surveillance in animals and humans.,2018 Dec 21,"['Pandit, Pranav S.', 'Doyle, Megan M.', 'Smart, Katrina M.', 'Young, Cristin C. W.', 'Drape, Gaylen W.', 'Johnson, Christine K.']",Nat Commun,,,False
fae708f3b0a6023fccad707c4417b521f84fc328,PMC,Predicting wildlife reservoirs and global vulnerability to zoonotic Flaviviruses,http://dx.doi.org/10.1038/s41467-018-07896-2,PMC6303316,30575757,CC BY,Flaviviruses continue to cause globally relevant epidemics and have emerged or re-emerged in regions that were previously unaffected. Factors determining emergence of flaviviruses and continuing circulation in sylvatic cycles are incompletely understood. Here we identify potential sylvatic reservoirs of flaviviruses and characterize the macro-ecological traits common to known wildlife hosts to predict the risk of sylvatic flavivirus transmission among wildlife and identify regions that could be vulnerable to outbreaks. We evaluate variability in wildlife hosts for zoonotic flaviviruses and find that flaviviruses group together in distinct clusters with similar hosts. Models incorporating ecological and climatic variables as well as life history traits shared by flaviviruses predict new host species with similar host characteristics. The combination of vector distribution data with models for flavivirus hosts allows for prediction of  global vulnerability to flaviviruses and provides potential targets for disease surveillance in animals and humans.,2018 Dec 21,"['Pandit, Pranav S.', 'Doyle, Megan M.', 'Smart, Katrina M.', 'Young, Cristin C. W.', 'Drape, Gaylen W.', 'Johnson, Christine K.']",Nat Commun,,,True
3ba1be6ad61854f68d5d05c1bd9b046479a9dafd,PMC,The first evidence of a new genotype of nephropathogenic infectious bronchitis virus circulating in vaccinated and unvaccinated broiler flocks in Algeria,http://dx.doi.org/10.14202/vetworld.2018.1630-1636,PMC6303496,30587900,CC BY,"BACKGROUND AND AIM: Avian infectious bronchitis virus (IBV) frequently infects broilers and is responsible for severe economic losses to the poultry industry worldwide. It has also been associated with kidney damage in the broiler flocks. The aim of the present study is to determine the presence of IBV and its possible involvement in kidney damage of broiler chicks. MATERIALS AND METHODS: 14 clinically diseased broiler flocks from Western and Central Algeria were sampled and analyzed by hemagglutination inhibition (HI) test and reverse transcriptase-polymerase chain reaction (RT-PCR) followed by phylogenic analysis. RESULTS: The QX (100%) and 4/91 (60%) IBV serotypes were the most prevalent in the kidney damaged broilers regardless of vaccination status. The molecular detection of avian IBV by RT-PCR identified six samples as positive, of which only two isolates were typable by sequencing. We identified a novel IBDZ13a genotype which showed 93% sequence homology to the partial-S1 gene sequence of the IB 4/91 commercial vaccine strain. Sequencing analysis characterized this virus as a novel and divergent IB 4/91 field virus with eight amino acid substitutions that might have resulted in altered immunogenicity. CONCLUSION: The isolation of a new IBV strain (IBDZ13a) from vaccinated broiler flocks may explain the failure of the vaccination programs against IBV field strains. Combination of the HI test and RT-PCR indicated that the nephropathogenic IB outbreaks in broilers are related to this novel strain.",2018 Nov 29,"['Lounas, A.', 'Oumouna-Benachour, K.', 'Medkour, H.', 'Oumouna, M.']",Vet World,,,True
533809638564f3d5ce4a13acd1ec0eaadf5bd05d,PMC,Self-contamination during doffing of personal protective equipment by healthcare workers to prevent Ebola transmission,http://dx.doi.org/10.1186/s13756-018-0433-y,PMC6303998,30607244,CC BY,"BACKGROUND: Healthcare workers (HCWs) use personal protective equipment (PPE) in Ebola virus disease (EVD) situations. However, preventing the contamination of HCWs and the environment during PPE removal crucially requires improved strategies. This study aimed to compare the efficacy of three PPE ensembles, namely, Hospital Authority (HA) Standard Ebola PPE set (PPE1), Dupont Tyvek Model, style 1422A (PPE2), and HA isolation gown for routine patient care and performing aerosol-generating procedures (PPE3) to prevent EVD transmission by measuring the degree of contamination of HCWs and the environment. METHODS: A total of 59 participants randomly performed PPE donning and doffing. The trial consisted of PPE donning, applying fluorescent solution on the PPE surface, PPE doffing of participants, and estimation of the degree of contamination as indicated by the number of fluorescent stains on the working clothes and environment. Protocol deviations during PPE donning and doffing were monitored. RESULTS: PPE2 and PPE3 presented higher contamination risks than PPE1. Environmental contaminations such as those originating from rubbish bin covers, chairs, faucets, and sinks were detected. Procedure deviations were observed during PPE donning and doffing, with PPE1 presenting the lowest overall deviation rate (%) among the three PPE ensembles (p < 0.05). CONCLUSION: Contamination of the subjects’ working clothes and surrounding environment occurred frequently during PPE doffing. Procedure deviations were observed during PPE donning and doffing. Although PPE1 presented a lower contamination risk than PPE2 and PPE3 during doffing and protocol deviations, the design of PPE1 can still be further improved. Future directions should focus on designing a high-coverage-area PPE with simple ergonomic features and on evaluating the doffing procedure to minimise the risk of recontamination. Regular training for users should be emphasised to minimise protocol deviations, and in turn, guarantee the best protection to HCWs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13756-018-0433-y) contains supplementary material, which is available to authorized users.",2018 Dec 22,"['Suen, Lorna K. P.', 'Guo, Yue Ping', 'Tong, Danny W. K.', 'Leung, Polly H. M.', 'Lung, David', 'Ng, Mandy S. P.', 'Lai, Timothy K. H.', 'Lo, Kiki Y. K.', 'Au-Yeung, Cypher H.', 'Yu, Winnie']",Antimicrob Resist Infect Control,,,True
883477472cfef01bbb0a10297e0f7268c0cee845,PMC,"Underweight, overweight, and obesity as independent risk factors for hospitalization in adults and children from influenza and other respiratory viruses",http://dx.doi.org/10.1111/irv.12618,PMC6304312,30515985,CC BY,"BACKGROUND: The relationship between obesity and risk of complications described during the 2009 influenza pandemic is poorly defined for seasonal influenza and other viral causes of influenza‐like illness (ILI). METHODS: An observational cohort of hospitalized and outpatient participants with ILI was conducted in six hospitals in Mexico. Nasopharyngeal swabs were tested for influenza and other common respiratory pathogens. RESULTS: A total of 4778 participants were enrolled in this study and had complete data. A total of 2053 (43.0%) had severe ILI. Seven hundred and seventy‐eight (16.3%) were positive for influenza, 2636 (55.2%) were positive for other viral respiratory pathogens, and 1364 (28.5%) had no respiratory virus isolated. Adults with influenza were more likely to be hospitalized if they were underweight (OR: 5.20), obese (OR: 3.18), or morbidly obese (OR: 18.40) compared to normal‐weight adults. Obese adults with H1N1 had a sixfold increase in odds of hospitalization over H3N2 and B (obese OR: 8.96 vs 1.35, morbidly obese OR: 35.13 vs 5.58, respectively) compared to normal‐weight adults. In adults with coronavirus, metapneumovirus, parainfluenza, and rhinovirus, participants that were underweight (OR: 4.07) and morbidly obese (OR: 2.78) were more likely to be hospitalized as compared to normal‐weight adults. All‐cause influenza‐like illness had a similar but less pronounced association between underweight or morbidly obesity and hospitalization. CONCLUSIONS: There is an increased risk of being hospitalized in adult participants that are underweight or morbidly obese, regardless of their viral pathogen status. Having influenza, however, significantly increases the odds of hospitalization in those who are underweight or morbidly obese.",2019 Jan 4,"['Moser, Joe‐Ann S.', 'Galindo‐Fraga, Arturo', 'Ortiz‐Hernández, Ana A.', 'Gu, Wenjuan', 'Hunsberger, Sally', 'Galán‐Herrera, Juan‐Francisco', 'Guerrero, María Lourdes', 'Ruiz‐Palacios, Guillermo M.', 'Beigel, John H.', None]",Influenza Other Respir Viruses,,,True
1efc2d5258eb4387f65e85a5b9bde50cdcd104fd,PMC,“Differential risk of hospitalization among single virus infections causing influenza‐like illnesses”,http://dx.doi.org/10.1111/irv.12606,PMC6304313,30137695,CC BY,"BACKGROUND: Acute respiratory infections are a major cause of morbidity in children and are often caused by viruses. However, the relative severity of illness associated with different viruses is unclear. The objective of this study was to evaluate the risk of hospitalization from different viruses in children presenting with an influenza‐like illness (ILI). METHODS: Data from children 5 years old or younger participating in an ILI natural history study from April 2010 to March 2014 was analyzed. The adjusted odds ratio for hospitalization was estimated in children with infections caused by respiratory syncytial virus (RSV), metapneumovirus, bocavirus, parainfluenza viruses, rhinovirus/enterovirus, coronavirus, adenovirus, and influenza. RESULTS: A total of 1486 children (408 outpatients and 1078 inpatients) were included in this analysis. At least one virus was detected in 1227 (82.6%) patients. The most frequent viruses detected as single pathogens were RSV (n = 286), rhinovirus/enterovirus (n = 251), parainfluenza viruses (n = 104), and influenza A or B (n = 99). After controlling for potential confounders (age, sex, recruitment site, days from symptom onset to enrollment, and underlying illnesses), children with RSV and metapneumovirus infections showed a greater likelihood of hospitalization than those infected by parainfluenza viruses (OR 2.7 and 1.9, respectively), rhinovirus/enterovirus (OR 3.1 and 2.1, respectively), coronaviruses (OR 4.9 and 3.4, respectively), adenovirus (OR 4.6 and 3.2, respectively), and influenza (OR 6.3 and 4.4, respectively). CONCLUSIONS: Children presenting with ILI caused by RSV and metapneumovirus were at greatest risk for hospitalization, while children with rhinovirus/enterovirus, parainfluenza, coronavirus, adenovirus, and influenza were at lower risk of hospitalization.",2019 Jan 16,"['Ortiz‐Hernández, Ana A.', 'Nishimura, Katherine K.', 'Noyola, Daniel E.', 'Moreno‐Espinosa, Sarbelio', 'Gamiño, Ana', 'Galindo‐Fraga, Arturo', 'Valdéz Vázquez, Rafael', 'Magaña Aquino, Martín', 'Ramirez‐Venegas, Alejandra', 'Valdés Salgado, Raydel', 'Andrade‐Platas, Diana', 'Estevez‐Jimenéz, Juliana', 'Ruiz‐Palacios, Guillermo M.', 'Guerrero, Maria Lourdes', 'Beigel, John', 'Smolskis, Mary C.', 'Hunsberger, Sally', 'Freimanis‐Hence, Laura', 'Llamosas‐Gallardo, Beatriz', None]",Influenza Other Respir Viruses,,,True
49fee1986467f0cff2bc3517dbc1570e52d069d3,PMC,"The impact of influenza infection on young children, their family and the health care system",http://dx.doi.org/10.1111/irv.12604,PMC6304317,30137663,CC BY,"BACKGROUND: Influenza is a major cause of respiratory illness in young children. Assessing the impact of infection on children and the community is required to guide immunisation policies. OBJECTIVES: To describe the impact of laboratory‐proven influenza in young children and to compare its impact with that of other respiratory viruses on the child, their family and the health care system. METHODS: Preschool children presenting for care or admission to a tertiary paediatric hospital during the 2008‐2014 influenza seasons were tested for respiratory virus by polymerase chain reaction and culture. Parental surveys were used to determine the impact of infection on illness duration, medication use, absenteeism and health service utilisation. Multivariate regression analyses were used to assess the impact of influenza and to evaluate the association between influenza status and outcomes. RESULTS: Among 1191 children assessed, 238 had influenza. Among children with influenza, 87.8% were administered antipyretics and 40.9% antibiotics. 28.6% had secondary complications. 65.4% of children missed school/day care, and 53.4% of parents missed work. When influenza and other viruses were compared, significant differences were noted including duration of illness (influenza: 9.54 days, other viruses: 8.50 days; P = 0.005) and duration of absenteeism for both the child (23.1 vs 17.3 hours; P = 0.015) and their parents (28.5 vs 22.7 hours; P = 0.012). CONCLUSIONS: Influenza infection in young children has a significant impact on medication use, absenteeism and the use of health care service. Significant differences are identified when compared with other ILI. These data demonstrate that influenza prevention strategies including immunisation are likely to have wide and significant impacts.",2019 Jan 11,"['Willis, Gabriela A.', 'Preen, David B.', 'Richmond, Peter C.', 'Jacoby, Peter', 'Effler, Paul V.', 'Smith, David W.', 'Robins, Christine', 'Borland, Meredith L.', 'Levy, Avram', 'Keil, Anthony D.', 'Blyth, Christopher C.', None]",Influenza Other Respir Viruses,,,True
3a6fd660f0d9555bdf2ba3b89120c82911386f51,PMC,Genome divergence and increased virulence of outbreak associated Salmonella enterica subspecies enterica serovar Heidelberg,http://dx.doi.org/10.1186/s13099-018-0279-0,PMC6304783,30603048,CC BY,"Salmonella enterica serotype Heidelberg is primarily a poultry adapted serotype of Salmonella that can also colonize other hosts and cause human disease. In this study, we compared the genomes of outbreak associated non-outbreak causing Salmonella ser. Heidelberg strains from diverse hosts and geographical regions. Human outbreak associated strains in this study were from a 2015 multistate outbreak of Salmonella ser. Heidelberg involving 15 states in the United States which originated from bull calves. Our clinicopathologic examination revealed that cases involving Salmonella ser. Heidelberg strains were predominantly young, less than weeks-old, dairy calves. Pre-existing or concurrent disease was found in the majority of the calves. Detection of Salmonella ser. Heidelberg correlated with markedly increased death losses clinically comparable to those seen in herds infected with S. Dublin, a known serious pathogen of cattle. Whole genome based single nucleotide polymorphism based analysis revealed that these calf isolates formed a distinct cluster along with outbreak associated human isolates. The defining feature of the outbreak associated strains, when compared to older isolates of S. Heidelberg, is that all isolates in this cluster contained Saf fimbrial genes which are generally absent in S. Heidelberg. The acquisition of several single nucleotide polymorphisms and the gain of Saf fimbrial genes may have contributed to the increased disease severity of these Salmonella ser. Heidelberg strains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13099-018-0279-0) contains supplementary material, which is available to authorized users.",2018 Dec 24,"['Antony, Linto', 'Behr, Melissa', 'Sockett, Donald', 'Miskimins, Dale', 'Aulik, Nicole', 'Christopher-Hennings, Jane', 'Nelson, Eric', 'Allard, Marc W.', 'Scaria, Joy']",Gut Pathog,,,True
70fe1da70b714ba14f71d217ecf93da18e291aa7,PMC,"Gene expression profiles alteration after infection of virus, bacteria, and parasite in the Olive flounder (Paralichthys olivaceus)",http://dx.doi.org/10.1038/s41598-018-36342-y,PMC6305387,30584247,CC BY,"Olive flounder (Paralichthys olivaceus) is one of economically valuable fish species in the East Asia. In comparison with its economic importance, available genomic information of the olive flounder is very limited. The mass mortality caused by variety of pathogens (virus, bacteria and parasites) is main problem in aquaculture industry, including in olive flounder culture. In this study, we carried out transcriptome analysis using the olive flounder gill tissues after infection of three types of pathogens (Virus; Viral hemorrhagic septicemia virus, Bacteria; Streptococcus parauberis, and Parasite; Miamiensis avidus), respectively. As a result, we identified total 12,415 differentially expressed genes (DEG) from viral infection, 1,754 from bacterial infection, and 795 from parasite infection, respectively. To investigate the effects of pathogenic infection on immune response, we analyzed Gene ontology (GO) enrichment analysis with DEGs and sorted immune-related GO terms per three pathogen groups. Especially, we verified various GO terms, and genes in these terms showed down-regulated expression pattern. In addition, we identified 67 common genes (10 up-regulated and 57 down-regulated) present in three pathogen infection groups. Our goals are to provide plenty of genomic knowledge about olive flounder transcripts for further research and report genes, which were changed in their expression after specific pathogen infection.",2018 Dec 24,"['Nam, Gyu-Hwi', 'Mishra, Anshuman', 'Gim, Jeong-An', 'Lee, Hee-Eun', 'Jo, Ara', 'Yoon, Dahye', 'Kim, Ahran', 'Kim, Woo-Jin', 'Ahn, Kung', 'Kim, Do-Hyung', 'Kim, Suhkmann', 'Cha, Hee-Jae', 'Choi, Yung Hyun', 'Park, Chan-Il', 'Kim, Heui-Soo']",Sci Rep,,,True
9e4f96618ed7ba4ba54c5c479ed595f1eb12fe9a,PMC,Preparation and Evaluation of Ribonuclease-Resistant Viral HIV RNA Standards Based on Armored RNA Technology,http://dx.doi.org/10.29252/.22.6.394,PMC6305816,29776310,CC BY,"BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) is an infectious viral agent that gradually extinguishes the immune system, resulting in acquired immune deficiency syndrome (AIDS). The aim of this study was to construct an RNA-positive control based on armored (AR) RNA technology, using HIV-1 RNA as a model. METHODS: The MS2 maturase, a coat protein gene (at positions 1765 to 1787) and HIV-1 pol gene were cloned into pET-32a plasmid. The prepared plasmid was transformed into Escherichia coli strain BL2 (DE3), and the expression of the construct was induced by 1 mM of isopropyl-L-thio-D-galactopyranoside (IPTG) at 37 °C for 16 h to obtain the fabricated AR RNA. The AR RNA was precipitated and purified using polyethylene glycol and Sephacryl S-200 chromatography. RESULTS: The stability of AR RNA was evaluated by treatment with DNase I and RNase A and confirmed by transmission electron microscopy and gel agarose electrophoresis. Tenfold serial dilution of AR RNA from 10(1) to 10(5) was prepared. Real-time PCR assays had a range of detection between 10(1) and 10(5). In addition, R(2) value was 0.998, and the slope of the standard curve was -3.33. CONCLUSION: Prepared AR RNA, as a positive control, could be used as a basis for launching an in-house HIV-1 virus assay and other infectious agents. It can be readily available to laboratories and HIV research centers. The AR RNA is non-infectious and highly resistant to ribonuclease enzyme and can reduce the risk of infection in the clinical laboratory.",2018 Nov,"['Gholami, Mohammad', 'Ravanshad, Mehrdad', 'Baesi, Kazem', 'Samiee, Siamak M.', 'Rozbahani, Negin Hosseini', 'Mohraz, Minoo']",Iran Biomed J,,,True
26ee25b06063d12c5685b764db2c72fbb17fc31f,PMC,Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum,http://dx.doi.org/10.1371/journal.pntd.0006977,PMC6306240,30540742,CC0,"BACKGROUND: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34(+) stem cells, (2) fetal derived liver, thymus and CD34(+) stem cells or (3) primary human skeletal muscle cells. NSG and humanized NSG mice were infected with 100 O. volvulus infective larvae (L3) for 4 to 12 weeks. When necropsies of infected animals were performed, it was observed that parasites survived and developed throughout the infection time course. In each of the different humanized mouse models, worms matured from L3 to advanced fourth stage larvae, with both male and female organ development. In addition, worms increased in length by up to 4-fold. Serum and urine, collected from humanized mice for identification of potential biomarkers of infection, allowed for the identification of 10 O. volvulus-derived proteins found specifically in either the urine or the serum of the humanized O. volvulus-infected NSG mice. CONCLUSIONS/SIGNIFICANCE: The newly identified mouse models for onchocerciasis will enable the development of O. volvulus specific biomarkers, screening for new therapeutic approaches and potentially studying the human immune response to infection with O. volvulus.",2018 Dec 12,"['Patton, John B.', 'Bennuru, Sasisekhar', 'Eberhard, Mark L.', 'Hess, Jessica A.', 'Torigian, April', 'Lustigman, Sara', 'Nutman, Thomas B.', 'Abraham, David']",PLoS Negl Trop Dis,,,True
c459e1a77d9256b02b2b9a5460fcfc8b420b753a,PMC,Fine Tuning the Cytokine Storm by IFN and IL-10 Following Neurotropic Coronavirus Encephalomyelitis,http://dx.doi.org/10.3389/fimmu.2018.03022,PMC6306494,30619363,CC BY,"The central nervous system (CNS) is vulnerable to several viral infections including herpes viruses, arboviruses and HIV to name a few. While a rapid and effective immune response is essential to limit viral spread and mortality, this anti-viral response needs to be tightly regulated in order to limit immune mediated tissue damage. This balance between effective virus control with limited pathology is especially important due to the highly specialized functions and limited regenerative capacity of neurons, which can be targets of direct virus cytolysis or bystander damage. CNS infection with the neurotropic strain of mouse hepatitis virus (MHV) induces an acute encephalomyelitis associated with focal areas of demyelination, which is sustained during viral persistence. Both innate and adaptive immune cells work in coordination to control virus replication. While type I interferons are essential to limit virus spread associated with early mortality, perforin, and interferon-γ promote further virus clearance in astrocytes/microglia and oligodendrocytes, respectively. Effective control of virus replication is nonetheless associated with tissue damage, characterized by demyelinating lesions. Interestingly, the anti-inflammatory cytokine IL-10 limits expansion of tissue lesions during chronic infection without affecting viral persistence. Thus, effective coordination of pro- and anti-inflammatory cytokines is essential during MHV induced encephalomyelitis in order to protect the host against viral infection at a limited cost.",2018 Dec 20,"['Savarin, Carine', 'Bergmann, Cornelia C.']",Front Immunol,,,True
72d786b072bf999b5925c527f2b1e8dcf326247e,PMC,Development and Assessment of a Diagnostic DNA Oligonucleotide Microarray for Detection and Typing of Meningitis-Associated Bacterial Species,http://dx.doi.org/10.3390/ht7040032,PMC6306750,30332776,CC BY,"Meningitis is commonly caused by infection with a variety of bacterial or viral pathogens. Acute bacterial meningitis (ABM) can cause severe disease, which can progress rapidly to a critical life-threatening condition. Rapid diagnosis of ABM is critical, as this is most commonly associated with severe sequelae with associated high mortality and morbidity rates compared to viral meningitis, which is less severe and self-limiting. We have designed a microarray for detection and diagnosis of ABM. This has been validated using randomly amplified DNA targets (RADT), comparing buffers with or without formamide, in glass slide format or on the Alere ArrayTube(TM) (Alere Technologies GmbH) microarray platform. Pathogen-specific signals were observed using purified bacterial nucleic acids and to a lesser extent using patient cerebral spinal fluid (CSF) samples, with some technical issues observed using RADT and glass slides. Repurposing the array onto the Alere ArrayTube(TM) platform and using a targeted amplification system increased specific and reduced nonspecific hybridization signals using both pathogen nucleic and patient CSF DNA targets, better revealing pathogen-specific signals although sensitivity was still reduced in the latter. This diagnostic microarray is useful as a laboratory diagnostic tool for species and strain designation for ABM, rather than for primary diagnosis.",2018 Oct 16,"['Bannister, Stephanie A.', 'Kidd, Stephen P.', 'Kirby, Elizabeth', 'Shah, Sonal', 'Thomas, Anvy', 'Vipond, Richard', 'Elmore, Michael J.', 'Telfer Brunton, Andrew', 'Marsh, Peter', 'Green, Steve', 'Silman, Nigel J.', 'Kempsell, Karen E.']",High Throughput,,,True
407207cc711d3067f35c04426fa4055ccb37ccfb,PMC,"Using Google Trends to Examine the Spatio-Temporal Incidence and Behavioral Patterns of Dengue Disease: A Case Study in Metropolitan Manila, Philippines",http://dx.doi.org/10.3390/tropicalmed3040118,PMC6306840,30423898,CC BY,"Dengue is a major public health concern and an economic burden in the Philippines. Despite the country’s improved dengue surveillance, it still suffers from various setbacks and needs to be complemented with alternative approaches. Previous studies have demonstrated the potential of Internet-based surveillance such as Google Dengue Trends (GDT) in supplementing current epidemiological methods for predicting future dengue outbreaks and patterns. With this, our study has two objectives: (1) assess the temporal relationship of weekly GDT and dengue incidence in Metropolitan Manila from 2009–2014; and (2) examine the health-seeking behavior based on dengue-related search queries of the population. The study collated the population statistics and reported dengue cases in Metropolitan Manila from respective government agencies to calculate the dengue incidence (DI) on a weekly basis for the entire region and annually per city. Data processing of GDT and dengue incidence was performed by conducting an ‘adjustment’ and scaling procedures, respectively, and further analyzed for correlation and cross-correlation analyses using Pearson’s correlation. The relative search volume of the term ‘dengue’ and top dengue-related search queries in Metropolitan Manila were obtained and organized from the Google Trends platform. Afterwards, a thematic analysis was employed, and word clouds were generated to examine the health behavior of the population. Results showed that weekly temporal GDT pattern are closely similar to the weekly DI pattern in Metropolitan Manila. Further analysis showed that GDT has a moderate and positive association with DI when adjusted or scaled, respectively. Cross-correlation analysis revealed a delayed effect where GDT leads DI by 1–2 weeks. Thematic analysis of dengue-related search queries indicated 5 categories namely; (a) dengue, (b) sign and symptoms of dengue, (c) treatment and prevention, (d) mosquito, and (e) other diseases. The majority of the search queries were classified in ‘signs and symptoms’ which indicate the health-seeking behavior of the population towards the disease. Therefore, GDT can be utilized to complement traditional disease surveillance methods combined with other factors that could potentially identify dengue hotspots and help in public health decisions.",2018 Nov 11,"['Ho, Howell T.', 'Carvajal, Thaddeus M.', 'Bautista, John Robert', 'Capistrano, Jayson Dale R.', 'Viacrusis, Katherine M.', 'Hernandez, Lara Fides T.', 'Watanabe, Kozo']",Trop Med Infect Dis,,,True
ca1825284bf301be00a4e4a79961d78ce9e9503c,PMC,"Using Google Trends to Examine the Spatio-Temporal Incidence and Behavioral Patterns of Dengue Disease: A Case Study in Metropolitan Manila, Philippines",http://dx.doi.org/10.3390/tropicalmed3040118,PMC6306840,30423898,CC BY,"Dengue is a major public health concern and an economic burden in the Philippines. Despite the country’s improved dengue surveillance, it still suffers from various setbacks and needs to be complemented with alternative approaches. Previous studies have demonstrated the potential of Internet-based surveillance such as Google Dengue Trends (GDT) in supplementing current epidemiological methods for predicting future dengue outbreaks and patterns. With this, our study has two objectives: (1) assess the temporal relationship of weekly GDT and dengue incidence in Metropolitan Manila from 2009–2014; and (2) examine the health-seeking behavior based on dengue-related search queries of the population. The study collated the population statistics and reported dengue cases in Metropolitan Manila from respective government agencies to calculate the dengue incidence (DI) on a weekly basis for the entire region and annually per city. Data processing of GDT and dengue incidence was performed by conducting an ‘adjustment’ and scaling procedures, respectively, and further analyzed for correlation and cross-correlation analyses using Pearson’s correlation. The relative search volume of the term ‘dengue’ and top dengue-related search queries in Metropolitan Manila were obtained and organized from the Google Trends platform. Afterwards, a thematic analysis was employed, and word clouds were generated to examine the health behavior of the population. Results showed that weekly temporal GDT pattern are closely similar to the weekly DI pattern in Metropolitan Manila. Further analysis showed that GDT has a moderate and positive association with DI when adjusted or scaled, respectively. Cross-correlation analysis revealed a delayed effect where GDT leads DI by 1–2 weeks. Thematic analysis of dengue-related search queries indicated 5 categories namely; (a) dengue, (b) sign and symptoms of dengue, (c) treatment and prevention, (d) mosquito, and (e) other diseases. The majority of the search queries were classified in ‘signs and symptoms’ which indicate the health-seeking behavior of the population towards the disease. Therefore, GDT can be utilized to complement traditional disease surveillance methods combined with other factors that could potentially identify dengue hotspots and help in public health decisions.",2018 Nov 11,"['Ho, Howell T.', 'Carvajal, Thaddeus M.', 'Bautista, John Robert', 'Capistrano, Jayson Dale R.', 'Viacrusis, Katherine M.', 'Hernandez, Lara Fides T.', 'Watanabe, Kozo']",Trop Med Infect Dis,,,False
f9a7674c9052c8a2db502ec640a9e9cd1d6cef34,PMC,Changing epidemiological patterns of HIV and AIDS in China in the post-SARS era identified by the nationwide surveillance system,http://dx.doi.org/10.1186/s12879-018-3551-5,PMC6307199,30587142,CC BY,"BACKGROUND: China has made substantial progress in tackling its HIV and AIDS epidemic. But the changing patterns of HIV and AIDS incidence based on the longitudinal observation data were rarely studied. METHODS: The reporting incidence (RI) and mortality data on HIV and AIDS in China covering 31 provinces from 2004 to 2014 were collected from the Chinese Public Health Science Data Center. To decompose the time-series data, Empirical Mode Decomposition (EMD) was applied to properly describe the trends of HIV and AIDS incidence. A mathematical model was used to estimate the relative change of incidence among provinces and age groups. RESULTS: A total of 483,010 newly HIV infections and 214,205 AIDS cases were reported between 2004 and 2014 nationwide. HIV infection increased from 13,258 in 2004 (RI 1.02 per 100,000 person years) to 74,048 in 2014 (RI 5.46 per 100,000). The number of AIDS cases increased from 3054 in 2004 (RI 0.23 per 100,000) to 45,145 in 2014 (RI 3.33 per 100,000). The overall relative changes for HIV infection and AIDS incidence were 1.11 (95% confidence interval [CI] 1.10–1.13) and 1.28 (95% CI 1.23–1.33), respectively. The relative increase for HIV and AIDS RI was higher in northwest provinces while lower in Henan, Xinjiang, Guangxi and Yunnan. The overall relative changes for HIV infection were 1.12 (95% CI 1.11–1.14) in males and 1.10 (95% CI 1.06–1.13) in females. For AIDS RI, the relative increases were 1.31 (95% CI 1.26–1.36) in males and 1.22 (95% CI 1.17–1.28) in females. The lowest relative increase was detected among young adults, while the largest relative increase (odds ratio [OR] > 1.30) was detected in people aged 55 years or above. CONCLUSIONS: HIV and AIDS showed an increasing trend in China from 2004 to 2014, respectively, but the epidemic tended to be under control among provinces and young people that used to have a high HIV and AIDS incidence. Northwest China and older people could be new “hop-spots” for HIV and AIDS risk.",2018 Dec 27,"['Liu, Zhenqiu', 'Shi, Oumin', 'Yan, Qiong', 'Fang, Qiwen', 'Zuo, Jialu', 'Chen, Yue', 'Chen, Xingdong', 'Zhang, Tiejun']",BMC Infect Dis,,,True
d660b285dc058ab74ce51cbd5179e01b9a6e8978,PMC,Detecting early‐warning signals of influenza outbreak based on dynamic network marker,http://dx.doi.org/10.1111/jcmm.13943,PMC6307766,30338927,CC BY,"The seasonal outbreaks of influenza infection cause globally respiratory illness, or even death in all age groups. Given early‐warning signals preceding the influenza outbreak, timely intervention such as vaccination and isolation management effectively decrease the morbidity. However, it is usually a difficult task to achieve the real‐time prediction of influenza outbreak due to its complexity intertwining both biological systems and social systems. By exploring rich dynamical and high‐dimensional information, our dynamic network marker/biomarker (DNM/DNB) method opens a new way to identify the tipping point prior to the catastrophic transition into an influenza pandemics. In order to detect the early‐warning signals before the influenza outbreak by applying DNM method, the historical information of clinic hospitalization caused by influenza infection between years 2009 and 2016 were extracted and assembled from public records of Tokyo and Hokkaido, Japan. The early‐warning signal, with an average of 4‐week window lead prior to each seasonal outbreak of influenza, was provided by DNM‐based on the hospitalization records, providing an opportunity to apply proactive strategies to prevent or delay the onset of influenza outbreak. Moreover, the study on the dynamical changes of hospitalization in local district networks unveils the influenza transmission dynamics or landscape in network level.",2019 Jan 19,"['Chen, Pei', 'Chen, Ely', 'Chen, Luonan', 'Zhou, Xianghong Jasmine', 'Liu, Rui']",J Cell Mol Med,,,True
ebdb4e508a69c6de68663ab53a00331abad6a19a,PMC,G-quadruplex forming sequences in the genome of all known human viruses: A comprehensive guide,http://dx.doi.org/10.1371/journal.pcbi.1006675,PMC6307822,30543627,CC BY,"G-quadruplexes are non-canonical nucleic-acid structures that control transcription, replication, and recombination in organisms. G-quadruplexes are present in eukaryotes, prokaryotes, and viruses. In the latter, mounting evidence indicates their key biological activity. Since data on viruses are scattered, we here present a comprehensive analysis of potential quadruplex-forming sequences (PQS) in the genome of all known viruses that can infect humans. We show that occurrence and location of PQSs are features characteristic of each virus class and family. Our statistical analysis proves that their presence within the viral genome is orderly arranged, as indicated by the possibility to correctly assign up to two-thirds of viruses to their exact class based on the PQS classification. For each virus we provide: i) the list of all PQS present in the genome (positive and negative strands), ii) their position in the viral genome, iii) the degree of conservation among strains of each PQS in its genome context, iv) the statistical significance of PQS abundance. This information is accessible from a database to allow the easy navigation of the results: http://www.medcomp.medicina.unipd.it/main_site/doku.php?id=g4virus. The availability of these data will greatly expedite research on G-quadruplex in viruses, with the possibility to accelerate finding therapeutic opportunities to numerous and some fearsome human diseases.",2018 Dec 13,"['Lavezzo, Enrico', 'Berselli, Michele', 'Frasson, Ilaria', 'Perrone, Rosalba', 'Palù, Giorgio', 'Brazzale, Alessandra R.', 'Richter, Sara N.', 'Toppo, Stefano']",PLoS Comput Biol,,,True
e0393328e9f59159671bff8a33e26edbdab28034,PMC,Intranasal immunization with Mycobacterium tuberculosis Rv3615c induces sustained adaptive CD4(+) T‐cell and antibody responses in the respiratory tract,http://dx.doi.org/10.1111/jcmm.13965,PMC6307849,30353641,CC BY,"Sustained adaptive immunity to pathogens provides effective protection against infections, and effector cells located at the site of infection ensure rapid response to the challenge. Both are essential for the success of vaccine development. To explore new vaccination approach against Mycobacterium tuberculosis (M.tb) infection, we have shown that Rv3615c, identified as ESX‐1 substrate protein C of M.tb but not expressed in BCG, induced a dominant Th1‐type response of CD4(+) T cells from patients with tuberculosis pleurisy, which suggests a potential candidate for vaccine development. But subcutaneous immunization with Rv3615c induced modest T‐cell responses systemically, and showed suboptimal protection against virulent M.tb challenge at the site of infection. Here, we use a mouse model to demonstrate that intranasal immunization with Rv3615c induces sustained capability of adaptive CD4(+) T‐ and B‐cell responses in lung parenchyma and airway. Rv3615c contains a dominant epitope of mouse CD4(+) T cells, Rv3615c(41‐50), and elicits CD4(+) T‐cell response with an effector–memory phenotype and multi‐Th1‐type cytokine coexpressions. Since T cells resident at mucosal tissue are potent at control of infection at early stage, our data show that intranasal immunization with Rv3615c promotes a sustained regional immunity to M.tb, and suggests a potency in control of M.tb infection. Our study warranties a further investigation of Rv3615c as a candidate for development of effective vaccination against M.tb infection.",2019 Jan 24,"['Li, Jiangping', 'Zhao, Jun', 'Shen, Juan', 'Wu, Changyou', 'Liu, Jie']",J Cell Mol Med,,,True
4c30f4001fb0068ba0b1444ea16b4d9cbe672996,PMC,TLR3 Regulated Poly I:C-Induced Neutrophil Extracellular Traps and Acute Lung Injury Partly Through p38 MAP Kinase,http://dx.doi.org/10.3389/fmicb.2018.03174,PMC6308186,30622526,CC BY,"Acute lung injury (ALI) is the leading cause of morbidity and mortality in critically ill patients. Neutrophil extracellular traps (NETs) have been well documented in the ALI model of bacterial infection. In the present study, we demonstrated that poly I:C could induce pulmonary NETs. Upon poly I:C intratracheal inoculation, neutrophil infiltration in the bronchoalveolar lavage fluid (BALF) was significantly increased. Furthermore, the inflammatory cytokines IL-1β, IL-6, and TNF-α in the lung were also significantly elevated. Neutrophil depletion abolished NETs and decreased both neutrophil infiltration and IL-1β in the lung. As expected, DNase I, an inhibitor of MPO and NADPH, decreased pulmonary inflammation and NETs. Blocking of the poly I:C receptor TLR3 reduced lung inflammation and NETs. The MAPK kinase inhibitor p38 diminished the formation of NETs and restored the expression of the tight junction protein claudin-5 in the mouse lung when challenged with poly I:C. In summary, poly I:C induced the formation of pulmonary NETs and ALI, which may be associated with the activation of p38 MAPK and the decreased expression of claudin-5.",2018 Dec 21,"['Gan, Tingting', 'Yang, Yonglin', 'Hu, Fan', 'Chen, Xichen', 'Zhou, Jiawei', 'Li, Yan', 'Xu, Ying', 'Wang, Huijuan', 'Chen, Yu', 'Zhang, Mingshun']",Front Microbiol,,,True
47d9a4720ad71e2f3fa79c9b54ff23ababcec330,PMC,Find the right sample: A study on the versatility of saliva and urine samples for the diagnosis of emerging viruses,http://dx.doi.org/10.1186/s12879-018-3611-x,PMC6311079,30594124,CC BY,"BACKGROUND: The emergence of different viral infections during the last decades like dengue, West Nile, SARS, chikungunya, MERS-CoV, Ebola, Zika and Yellow Fever raised some questions on quickness and reliability of laboratory diagnostic tests for verification of suspected cases. Since sampling of blood requires medically trained personal and comprises some risks for the patient as well as for the health care personal, the sampling by non-invasive methods (e.g. saliva and/ or urine) might be a very valuable alternative for investigating a diseased patient. MAIN BODY: To analyse the usefulness of alternative non­invasive samples for the diagnosis of emerging infectious viral diseases, a literature search was performed on PubMed for alternative sampling for these viral infections. In total, 711 papers of potential relevance were found, of which we have included 128 in this review. CONCLUSIONS: Considering the experience using non-invasive sampling for the diagnostic of emerging viral diseases, it seems important to perform an investigation using alternative samples for routine diagnostics. Moreover, during an outbreak situation, evaluation of appropriate sampling and further processing for laboratory analysis on various diagnostic platforms are very crucial. This will help to achieve optimal diagnostic results for a good and reliable case identification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3611-x) contains supplementary material, which is available to authorized users.",2018 Dec 29,"['Niedrig, Matthias', 'Patel, Pranav', 'El Wahed, Ahmed Abd', 'Schädler, Regina', 'Yactayo, Sergio']",BMC Infect Dis,,,True
22b2cb7ff5ea6e57e41098d8cf66aa69a5d04bc4,PMC,Oxidative Stress in Poultry: Lessons from the Viral Infections,http://dx.doi.org/10.1155/2018/5123147,PMC6311761,30647810,CC BY,"Reactive species (RS), generally known as reactive oxygen species (ROS) and reactive nitrogen species (RNS), are produced during regular metabolism in the host and are required for many cellular processes such as cytokine transcription, immunomodulation, ion transport, and apoptosis. Intriguingly, both RNS and ROS are commonly triggered by the pathogenic viruses and are famous for their dual roles in the clearance of viruses and pathological implications. Uncontrolled production of reactive species results in oxidative stress and causes damage in proteins, lipids, DNA, and cellular structures. In this review, we describe the production of RS, their detoxification by a cellular antioxidant system, and how these RS damage the proteins, lipids, and DNA. Given the widespread importance of RS in avian viral diseases, oxidative stress pathways are of utmost importance for targeted therapeutics. Therefore, a special focus is provided on avian virus-mediated oxidative stresses. Finally, future research perspectives are discussed on the exploitation of these pathways to treat viral diseases of poultry.",2018 Dec 10,"['Rehman, Zaib Ur', 'Meng, Chunchun', 'Sun, Yingjie', 'Safdar, Anum', 'Pasha, Riaz Hussain', 'Munir, Muhammad', 'Ding, Chan']",Oxid Med Cell Longev,,,True
1b08674379f9805e1ab55ce13c056b716433b8a2,PMC,A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies,http://dx.doi.org/10.1371/journal.pcbi.1006554,PMC6312344,30557340,CC BY,"Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.",2018 Dec 17,"['Cori, Anne', 'Nouvellet, Pierre', 'Garske, Tini', 'Bourhy, Hervé', 'Nakouné, Emmanuel', 'Jombart, Thibaut']",PLoS Comput Biol,,,True
fc26cafc8843bb3223e9e9af13a91df3b9274ea6,PMC,A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies,http://dx.doi.org/10.1371/journal.pcbi.1006554,PMC6312344,30557340,CC BY,"Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.",2018 Dec 17,"['Cori, Anne', 'Nouvellet, Pierre', 'Garske, Tini', 'Bourhy, Hervé', 'Nakouné, Emmanuel', 'Jombart, Thibaut']",PLoS Comput Biol,,,True
8ddd20980cff641091f4bd008fca3fc922f7a9ec,PMC,A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies,http://dx.doi.org/10.1371/journal.pcbi.1006554,PMC6312344,30557340,CC BY,"Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.",2018 Dec 17,"['Cori, Anne', 'Nouvellet, Pierre', 'Garske, Tini', 'Bourhy, Hervé', 'Nakouné, Emmanuel', 'Jombart, Thibaut']",PLoS Comput Biol,,,False
7154a3fc120086fb8f5657238444e5ea61b8dfa3,PMC,A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies,http://dx.doi.org/10.1371/journal.pcbi.1006554,PMC6312344,30557340,CC BY,"Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.",2018 Dec 17,"['Cori, Anne', 'Nouvellet, Pierre', 'Garske, Tini', 'Bourhy, Hervé', 'Nakouné, Emmanuel', 'Jombart, Thibaut']",PLoS Comput Biol,,,False
53549371821470dbcbeafb9d29e90f3667f71885,PMC,A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies,http://dx.doi.org/10.1371/journal.pcbi.1006554,PMC6312344,30557340,CC BY,"Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.",2018 Dec 17,"['Cori, Anne', 'Nouvellet, Pierre', 'Garske, Tini', 'Bourhy, Hervé', 'Nakouné, Emmanuel', 'Jombart, Thibaut']",PLoS Comput Biol,,,False
6bf6057590766cae3a3c627536e8609af1de2ecd,PMC,A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies,http://dx.doi.org/10.1371/journal.pcbi.1006554,PMC6312344,30557340,CC BY,"Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.",2018 Dec 17,"['Cori, Anne', 'Nouvellet, Pierre', 'Garske, Tini', 'Bourhy, Hervé', 'Nakouné, Emmanuel', 'Jombart, Thibaut']",PLoS Comput Biol,,,False
c3e4b2b8b57fcab538193ccd493b5b4a2efe16ac,PMC,A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies,http://dx.doi.org/10.1371/journal.pcbi.1006554,PMC6312344,30557340,CC BY,"Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.",2018 Dec 17,"['Cori, Anne', 'Nouvellet, Pierre', 'Garske, Tini', 'Bourhy, Hervé', 'Nakouné, Emmanuel', 'Jombart, Thibaut']",PLoS Comput Biol,,,False
c6dd33ed7524321b1189d3733b38f4f20bda2bb3,PMC,A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies,http://dx.doi.org/10.1371/journal.pcbi.1006554,PMC6312344,30557340,CC BY,"Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.",2018 Dec 17,"['Cori, Anne', 'Nouvellet, Pierre', 'Garske, Tini', 'Bourhy, Hervé', 'Nakouné, Emmanuel', 'Jombart, Thibaut']",PLoS Comput Biol,,,False
50d49b2358a28c38a04c0c47bdf77f7fab18dd7d,PMC,A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies,http://dx.doi.org/10.1371/journal.pcbi.1006554,PMC6312344,30557340,CC BY,"Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.",2018 Dec 17,"['Cori, Anne', 'Nouvellet, Pierre', 'Garske, Tini', 'Bourhy, Hervé', 'Nakouné, Emmanuel', 'Jombart, Thibaut']",PLoS Comput Biol,,,False
4f55a2098a81c738e05407ac04024c7b5a918ab2,PMC,A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies,http://dx.doi.org/10.1371/journal.pcbi.1006554,PMC6312344,30557340,CC BY,"Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.",2018 Dec 17,"['Cori, Anne', 'Nouvellet, Pierre', 'Garske, Tini', 'Bourhy, Hervé', 'Nakouné, Emmanuel', 'Jombart, Thibaut']",PLoS Comput Biol,,,False
bd78ebd38103e3e938b3946c947249f42a3d8118,PMC,A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies,http://dx.doi.org/10.1371/journal.pcbi.1006554,PMC6312344,30557340,CC BY,"Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.",2018 Dec 17,"['Cori, Anne', 'Nouvellet, Pierre', 'Garske, Tini', 'Bourhy, Hervé', 'Nakouné, Emmanuel', 'Jombart, Thibaut']",PLoS Comput Biol,,,False
f27798a8d00c1db712876dd86fdffa56834b2534,PMC,A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies,http://dx.doi.org/10.1371/journal.pcbi.1006554,PMC6312344,30557340,CC BY,"Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.",2018 Dec 17,"['Cori, Anne', 'Nouvellet, Pierre', 'Garske, Tini', 'Bourhy, Hervé', 'Nakouné, Emmanuel', 'Jombart, Thibaut']",PLoS Comput Biol,,,False
bf4b388eacfe02baac318ddc3b47eba5095d6b4b,PMC,A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies,http://dx.doi.org/10.1371/journal.pcbi.1006554,PMC6312344,30557340,CC BY,"Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.",2018 Dec 17,"['Cori, Anne', 'Nouvellet, Pierre', 'Garske, Tini', 'Bourhy, Hervé', 'Nakouné, Emmanuel', 'Jombart, Thibaut']",PLoS Comput Biol,,,False
4fbe77239a5ef0312e0e8a9e71e7be9926246b4b,PMC,A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies,http://dx.doi.org/10.1371/journal.pcbi.1006554,PMC6312344,30557340,CC BY,"Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.",2018 Dec 17,"['Cori, Anne', 'Nouvellet, Pierre', 'Garske, Tini', 'Bourhy, Hervé', 'Nakouné, Emmanuel', 'Jombart, Thibaut']",PLoS Comput Biol,,,False
e400519e29371d29d906875f8b2de776c16b477b,PMC,A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies,http://dx.doi.org/10.1371/journal.pcbi.1006554,PMC6312344,30557340,CC BY,"Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.",2018 Dec 17,"['Cori, Anne', 'Nouvellet, Pierre', 'Garske, Tini', 'Bourhy, Hervé', 'Nakouné, Emmanuel', 'Jombart, Thibaut']",PLoS Comput Biol,,,False
597640eefa297ba3699d59bfb1df8a2c81e0d19b,PMC,A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies,http://dx.doi.org/10.1371/journal.pcbi.1006554,PMC6312344,30557340,CC BY,"Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.",2018 Dec 17,"['Cori, Anne', 'Nouvellet, Pierre', 'Garske, Tini', 'Bourhy, Hervé', 'Nakouné, Emmanuel', 'Jombart, Thibaut']",PLoS Comput Biol,,,False
1b21437159e00cfbc7a48cfb1cc4c27a818e2157,PMC,Robustness of the reproductive number estimates in vector-borne disease systems,http://dx.doi.org/10.1371/journal.pntd.0006999,PMC6312349,30557351,CC BY,"BACKGROUND: The required efforts, feasibility and predicted success of an intervention strategy against an infectious disease are partially determined by its basic reproduction number, R(0). In its simplest form R(0) can be understood as the product of the infectious period, the number of infectious contacts and the per-contact transmission probability, which in the case of vector-transmitted diseases necessarily extend to the vector stages. As vectors do not usually recover from infection, they remain infectious for life, which places high significance on the vector’s life expectancy. Current methods for estimating the R(0) for a vector-borne disease are mostly derived from compartmental modelling frameworks assuming constant vector mortality rates. We hypothesised that some of the assumptions underlying these models can lead to unrealistic high vector life expectancies with important repercussions for R(0) estimates. METHODOLOGY AND PRINCIPAL FINDINGS: Here we used a stochastic, individual-based model which allowed us to directly measure the number of secondary infections arising from one index case under different assumptions about vector mortality. Our results confirm that formulas based on age-independent mortality rates can overestimate R(0) by nearly 100% compared to our own estimate derived from first principles. We further provide a correction factor that can be used with a standard R(0) formula and adjusts for the discrepancies due to erroneous vector age distributions. CONCLUSION: Vector mortality rates play a crucial role for the success and general epidemiology of vector-transmitted diseases. Many modelling efforts intrinsically assume these to be age-independent, which, as clearly demonstrated here, can lead to severe over-estimation of the disease’s reproduction number. Our results thus re-emphasise the importance of obtaining field-relevant and species-dependent vector mortality rates, which in turn would facilitate more realistic intervention impact predictions.",2018 Dec 17,"['Tennant, Warren', 'Recker, Mario']",PLoS Negl Trop Dis,,,True
db459b8a4b49c8b1ad883d0824c6bffccefb525e,PMC,Robustness of the reproductive number estimates in vector-borne disease systems,http://dx.doi.org/10.1371/journal.pntd.0006999,PMC6312349,30557351,CC BY,"BACKGROUND: The required efforts, feasibility and predicted success of an intervention strategy against an infectious disease are partially determined by its basic reproduction number, R(0). In its simplest form R(0) can be understood as the product of the infectious period, the number of infectious contacts and the per-contact transmission probability, which in the case of vector-transmitted diseases necessarily extend to the vector stages. As vectors do not usually recover from infection, they remain infectious for life, which places high significance on the vector’s life expectancy. Current methods for estimating the R(0) for a vector-borne disease are mostly derived from compartmental modelling frameworks assuming constant vector mortality rates. We hypothesised that some of the assumptions underlying these models can lead to unrealistic high vector life expectancies with important repercussions for R(0) estimates. METHODOLOGY AND PRINCIPAL FINDINGS: Here we used a stochastic, individual-based model which allowed us to directly measure the number of secondary infections arising from one index case under different assumptions about vector mortality. Our results confirm that formulas based on age-independent mortality rates can overestimate R(0) by nearly 100% compared to our own estimate derived from first principles. We further provide a correction factor that can be used with a standard R(0) formula and adjusts for the discrepancies due to erroneous vector age distributions. CONCLUSION: Vector mortality rates play a crucial role for the success and general epidemiology of vector-transmitted diseases. Many modelling efforts intrinsically assume these to be age-independent, which, as clearly demonstrated here, can lead to severe over-estimation of the disease’s reproduction number. Our results thus re-emphasise the importance of obtaining field-relevant and species-dependent vector mortality rates, which in turn would facilitate more realistic intervention impact predictions.",2018 Dec 17,"['Tennant, Warren', 'Recker, Mario']",PLoS Negl Trop Dis,,,True
1341e9e33488d304353f31081a8422ed8715b5b6,PMC,Host-Driven Phosphorylation Appears to Regulate the Budding Activity of the Lassa Virus Matrix Protein,http://dx.doi.org/10.3390/pathogens7040097,PMC6313517,30544850,CC BY,"Lassa mammarenavirus (LASV) is an enveloped RNA virus that can cause Lassa fever, an acute hemorrhagic fever syndrome associated with significant morbidity and high rates of fatality in endemic regions of western Africa. The arenavirus matrix protein Z has several functions during the virus life cycle, including coordinating viral assembly, driving the release of new virus particles, regulating viral polymerase activity, and antagonizing the host antiviral response. There is limited knowledge regarding how the various functions of Z are regulated. To investigate possible means of regulation, mass spectrometry was used to identify potential sites of phosphorylation in the LASV Z protein. This analysis revealed that two serines (S18, S98) and one tyrosine (Y97) are phosphorylated in the flexible N- and C-terminal regions of the protein. Notably, two of these sites, Y97 and S98, are located in (Y97) or directly adjacent to (S98) the PPXY late domain, an important motif for virus release. Studies with non-phosphorylatable and phosphomimetic Z proteins revealed that these sites are important regulators of the release of LASV particles and that host-driven, reversible phosphorylation may play an important role in the regulation of LASV Z protein function.",2018 Dec 9,"['Ziegler, Christopher M.', 'Eisenhauer, Philip', 'Manuelyan, Inessa', 'Weir, Marion E.', 'Bruce, Emily A.', 'Ballif, Bryan A.', 'Botten, Jason']",Pathogens,,,True
03b0692ffcc41cf157797f5750d4c4ad3c7c2139,PMC,Host-Driven Phosphorylation Appears to Regulate the Budding Activity of the Lassa Virus Matrix Protein,http://dx.doi.org/10.3390/pathogens7040097,PMC6313517,30544850,CC BY,"Lassa mammarenavirus (LASV) is an enveloped RNA virus that can cause Lassa fever, an acute hemorrhagic fever syndrome associated with significant morbidity and high rates of fatality in endemic regions of western Africa. The arenavirus matrix protein Z has several functions during the virus life cycle, including coordinating viral assembly, driving the release of new virus particles, regulating viral polymerase activity, and antagonizing the host antiviral response. There is limited knowledge regarding how the various functions of Z are regulated. To investigate possible means of regulation, mass spectrometry was used to identify potential sites of phosphorylation in the LASV Z protein. This analysis revealed that two serines (S18, S98) and one tyrosine (Y97) are phosphorylated in the flexible N- and C-terminal regions of the protein. Notably, two of these sites, Y97 and S98, are located in (Y97) or directly adjacent to (S98) the PPXY late domain, an important motif for virus release. Studies with non-phosphorylatable and phosphomimetic Z proteins revealed that these sites are important regulators of the release of LASV particles and that host-driven, reversible phosphorylation may play an important role in the regulation of LASV Z protein function.",2018 Dec 9,"['Ziegler, Christopher M.', 'Eisenhauer, Philip', 'Manuelyan, Inessa', 'Weir, Marion E.', 'Bruce, Emily A.', 'Ballif, Bryan A.', 'Botten, Jason']",Pathogens,,,False
0b14aca39651cc93fb2ca56a4ab433f57716ca37,PMC,Infections in Healthcare Workers in Germany—22-Year Time Trends †,http://dx.doi.org/10.3390/ijerph15122656,PMC6313552,30486322,CC BY,"Health workers (HWs) run an increased risk of infection. The standardised data set of an accident insurer was used to analyse the time trends of infection-related claims and confirmed occupational diseases (ODs) in HWs. The numbers of claims and confirmed claims for different infections were analysed for the years 1996 to 2017. The rate of claims and confirmed ODs were calculated per 100,000 full-time workers. The number of claims was relatively stable over time. However, the rate per 100,000 full-time workers decreased from 25.2 to 15.4. The decrease was most pronounced for hepatitis B and hepatitis C infections, which were the most frequent infections for which claims were made at the start of the period. In 2017, tuberculosis (TB)-related claims were more frequent than those related to blood-borne virus infections. However, the growing number of TB claims does not reflect an increased infection risk, but rather improved methods for the diagnosis of latent TB infection (LTBI). Measures to prevent blood-borne virus infections in HWs were successful in the last 22 years, but attention should be paid to newly emerging infections.",2018 Dec 26,"Nienhaus, Albert",Int J Environ Res Public Health,,,True
19f5eb39de2aef11b4e3b8c0fa4b92f048057d83,PMC,Airflow as a Possible Transmission Route of Middle East Respiratory Syndrome at an Initial Outbreak Hospital in Korea,http://dx.doi.org/10.3390/ijerph15122757,PMC6313554,30563206,CC BY,"In this study, the results of an airflow investigation conducted on 7 June 2015 as part of a series of epidemiologic investigations at Pyeongtaek St. Mary’s Hospital, South Korea, were investigated. The study involved 38 individuals who were infected directly and indirectly with Middle East Respiratory Syndrome (MERS), by a super-spreader patient. Tracer gas experiments conducted on the eighth floor, where the initial patient was hospitalized, confirmed that the tracer gas spread to adjacent patient rooms and rooms across corridors. In particular, the experiment with an external wind direction and speed similar to those during the hospitalization of the initial patient revealed that the air change rate was 17–20 air changes per hour (ACH), with air introduced through the window in the room of the infected patient (room 8104). The tracer gas concentration of room 8110, which was the farthest room, was 7.56% of room 8104, indicating that a high concentration of gas has spread from room 8104 to rooms across the corridor. In contrast, the tracer gas was barely detected in a maternity ward to the south of room 8104, where there was no secondary infected patient. Moreover, MERS is known to spread mainly by droplets through close contact, but long-distance dispersion is probable in certain environments, such as that of a super-spreader patient hospitalized in a room without ventilation, hospitals with a central corridor type, and indoor airflow dispersion due to external wind.",2018 Dec 6,"['Sung, Minki', 'Jo, Seongmin', 'Lee, Sang-Eun', 'Ki, Moran', 'Choi, Bo Youl', 'Hong, JinKwan']",Int J Environ Res Public Health,,,True
a95452bb03845776e74c5af3dd628cb5c25a02aa,PMC,Dogs (Canis familiaris) as Sentinels for Human Infectious Disease and Application to Canadian Populations: A Systematic Review,http://dx.doi.org/10.3390/vetsci5040083,PMC6313866,30248931,CC BY,"In a world where climate change, vector expansion, human activity, and pathogen dispersal do not respect boundaries, the human–animal–pathogen interface has become less defined. Consequently, a One Health approach to disease surveillance and control has generated much interest across several disciplines. This systematic review evaluates current global research on the use of domestic dogs as sentinels for human infectious disease, and critically appraises how this may be applied within Canada. Results highlighted a bias in research from high- and middle-income-economy countries, with 35% of the studies describing data from the Latin America/Caribbean region, 25% from North America, and 11% from the European/Central Asia region. Bacteria were the most studied type of infectious agent, followed by protozoa, viruses, helminths, and fungi. Only six out of 142 studies described disease in Canada: four researched a variety of pathogens within Indigenous communities, one researched Borrelia burgdorferi in British Columbia, and one researched arboviruses in Quebec. Results from this review suggest that dogs could provide excellent sentinels for certain infectious-disease pathogens in Canada, yet are currently overlooked. Further research into the use of dog-sentinel surveillance is specifically recommended for California serogroup viruses, Chikungunya virus, West Nile virus, Lyme borreliosis, Rickettsia spp., Ehrlichia spp., and Dirofilaria immitis.",2018 Sep 21,"['Bowser, Natasha H.', 'Anderson, Neil E.']",Vet Sci,,,True
88b18a2771249ead085fdebfab0aea7839176e05,PMC,Assay Challenges for Emerging Infectious Diseases: The Zika Experience,http://dx.doi.org/10.3390/vaccines6040070,PMC6313918,30279372,CC BY,"From the perspective of vaccine development, it is imperative to accurately diagnose target infections in order to exclude subjects with prior exposure from evaluations of vaccine effectiveness, to track incident infection during the course of a clinical trial and to differentiate immune reactions due to natural infections from responses that are vaccine related. When vaccine development is accelerated to a rapid pace in response to emerging infectious disease threats, the challenges to develop such diagnostic tools is even greater. This was observed through the recent expansion of Zika virus infections into the Western Hemisphere in 2014–2017. When initial Zika vaccine clinical trials were being designed and launched in response to the outbreak, there were no standardized sets of viral and immunological assays, and no approved diagnostic tests for Zika virus infection. The diagnosis of Zika virus infection is still an area of active research and development on many fronts. Here we review emerging infectious disease vaccine clinical assay development and trial execution with a special focus on the state of Zika virus clinical assays and diagnostics.",2018 Oct 2,"['Roberts, Christine C.', 'Maslow, Joel N.']",Vaccines (Basel),,,True
e2cef67ca136f4b301736031caac1aa1085abcb6,PMC,The Safety of an Adjuvanted Autologous Cancer Vaccine Platform in Canine Cancer Patients,http://dx.doi.org/10.3390/vetsci5040087,PMC6313922,30322015,CC BY,"Canine cancer rates are similar to humans, though the therapeutic options might be limited. Inducing a patient’s own immune system to have an anti-tumor response is an attractive approach to cancer therapy. In this safety study, autologous tumor vaccines produced specifically for each canine patient were combined with Advax™, a novel non-inflammatory immunomodulator and vaccine adjuvant and were tested for safety in a diverse range of patient presentations alone or in combination with other treatments. Canine patients had their tumor biopsied, debulked or resected and the tumor antigens were processed into an autologous vaccine formulated with Advax™ adjuvant with or without rhizavidin as an additional immune stimulant. Patients treated early in the trial received two intramuscular (IM) doses, 2 weeks apart. As the study progressed and no issues of safety were observed, the protocol was changed to weekly vaccinations for 4 weeks followed by monthly booster shots. Over the 150 I.M injections delivered to date, the vaccine was found to be very safe and no significant adverse reactions were observed. These results justify ongoing development and future controlled studies of this autologous vaccine approach.",2018 Oct 12,"['Weir, Chris', 'Oksa, Annika', 'Millar, Jennifer', 'Alexander, Miles', 'Kynoch, Nicola', 'Walton-Weitz, Zoe', 'Mackenzie-Wood, Peter', 'Tam, Felicia', 'Richards, Hope', 'Naylor, Richard', 'Cheng, Katrina', 'Bennett, Peter', 'Petrovsky, Nikolai', 'Allavena, Rachel']",Vet Sci,,,True
e5c06914d0daee6e881665b23adca340d0a6271a,PMC,Impact of glucose-6-phosphate dehydrogenase deficiency on dengue infection in Myanmar children,http://dx.doi.org/10.1371/journal.pone.0209204,PMC6314580,30601843,CC BY,"Glucose-6-phosphate dehydrogenase (G6PD) deficiency may affect the clinical presentation of dengue due to the altered redox state in immune cells. We aimed to determine the association between G6PD deficiency and severity of dengue infection in paediatric patients in Myanmar. A cross-sectional study was conducted among paediatric patients aged 2–13 years with dengue in Yankin Children Hospital, Myanmar. One hundred and ninety-six patients positive for dengue infection, as determined via PCR or ELISA, were enrolled. Dengue severity was determined according to the 2009 WHO classification guidelines. Spectrophotometric assays determined G6PD levels. The adjusted median G6PD value of males in the study population was used to define various cut-off points according to the WHO classification guidelines. G6PD genotyping for Mahidol, Kaiping and Mediterranean mutations was performed for 128 out of 196 samples by real-time multiplex PCR. 51 of 196 (26.0%) patients had severe dengue. The prevalence of G6PD phenotype deficiency (< 60% activity) in paediatric patients was 14.8% (29/196), specifically, 13.6% (14/103) in males and 16.2% (15/93) in females. Severe deficiency (< 10% activity) accounted for 7.1% (14/196) of our cohort, occurring 11.7% (12/103) in males and 2.2% (2/93) in females. Among 128 samples genotyped, the G6PD gene mutations were detected in 19.5% (25/128) of patients, with 20.3% (13/ 64) in males and 18.8% (12/64) in females. The G6PD Mahidol mutation was 96.0% (24/25) while the G6PD Kaiping mutation was 4.0% (1/25). Severe dengue was not associated with G6PD enzyme deficiency or presence of the G6PD gene mutation. Thus, no association between G6PD deficiency and dengue severity could be detected. Trial registration: The study was registered following the WHO International Clinical Trials Registry Platform (WHO-ICTRP) on Thai Clinical Trials Registry (TCTR) website, registration number # TCTR20180720001",2019 Jan 2,"['May, Win Lai', 'Kyaw, Myat Phone', 'Blacksell, Stuart D.', 'Pukrittayakamee, Sasithon', 'Chotivanich, Kesinee', 'Hanboonkunupakarn, Borimas', 'Thein, Khin Nyo', 'Lim, Chae Seung', 'Thaipadungpanit, Janjira', 'Althaus, Thomas', 'Jittamala, Podjanee']",PLoS One,,,True
75bee23cd59f44b79301f951a5627c47a1adcee3,PMC,Venezuelan Equine Encephalitis Virus Capsid Implicated in Infection-Induced Cell Cycle Delay in vitro,http://dx.doi.org/10.3389/fmicb.2018.03126,PMC6315117,30631316,CC BY,"Venezuelan equine encephalitis virus (VEEV) is a positive sense, single-stranded RNA virus and member of the New World alphaviruses. It causes a biphasic febrile illness that can be accompanied by central nervous system involvement and moderate morbidity in humans and severe mortality in equines. The virus has a history of weaponization, lacks FDA-approved therapeutics and vaccines in humans, and is considered a select agent. Like other RNA viruses, VEEV replicates in the cytoplasm of infected cells and eventually induces apoptosis. The capsid protein, which contains a nuclear localization and a nuclear export sequence, induces a shutdown of host transcription and nucleocytoplasmic trafficking. Here we show that infection with VEEV causes a dysregulation of cell cycling and a delay in the G(0)/G(1) phase in Vero cells and U87MG astrocytes. Cells infected with VEEV encoding a capsid NLS mutant or treated with the capsid-importin α interaction inhibitor G281-1485 were partially rescued from this cell cycle dysregulation. Pathway analysis of previously published RNA-sequencing data from VEEV infected U87MG astrocytes identified alterations of canonical pathways involving cell cycle, checkpoint regulation, and proliferation. Multiple cyclins including cyclin D1, cyclin A2 and cyclin E2 and other regulators of the cell cycle were downregulated in infected cells in a capsid NLS dependent manner. Loss of Rb phosphorylation, which is a substrate for cyclin/cdk complexes was also observed. These data demonstrate the importance of capsid nuclear localization and/or importin α binding for inducing cell cycle arrest and transcriptional downregulation of key cell cycle regulators.",2018 Dec 18,"['Lundberg, Lindsay', 'Fontenot, Jacque', 'Lin, Shih-Chao', 'Pinkham, Chelsea', 'Carey, Brian D.', 'Campbell, Catherine E.', 'Kehn-Hall, Kylene']",Front Microbiol,,,True
1fb1a2388d4c9483abb1b390bb0410c941bfd1b7,PMC,Current Knowledge on Porcine circovirus 3 (PCV-3): A Novel Virus With a Yet Unknown Impact on the Swine Industry,http://dx.doi.org/10.3389/fvets.2018.00315,PMC6315159,30631769,CC BY,"Porcine circovirus 3 (PCV-3) is a recently described virus belonging to the family Circoviridae. It represents the third member of genus Circovirus able to infect swine, together with PCV-1, considered non-pathogenic, and PCV-2, one of the most economically relevant viruses for the swine worldwide industry. PCV-3 was originally found by metagenomics analyses in 2015 in tissues of pigs suffering from porcine dermatitis and nephropathy syndrome, reproductive failure, myocarditis and multisystemic inflammation. The lack of other common pathogens as potential infectious agents of these conditions prompted the suspicion that PCV-3 might etiologically be involved in disease occurrence. Subsequently, viral genome was detected in apparently healthy pigs, and retrospective studies indicated that PCV-3 was already present in pigs by early 1990s. In fact, current evidence suggests that PCV-3 is a rather widespread virus worldwide. Recently, the virus DNA has also been found in wild boar, expanding the scope of infection susceptibility among the Suidae family; also, the potential reservoir role of this species for the domestic pig has been proposed. Phylogenetic studies with available PCV-3 partial and complete sequences from around the world have revealed high nucleotide identity (>96%), although two main groups and several subclusters have been described as well. Moreover, it has been proposed the existence of a most common ancestor dated around 50 years ago. Taking into account the economic importance and the well-known effects of PCV-2 on the swine industry, a new member of the same family like PCV-3 should not be neglected. Studies on epidemiology, pathogenesis, immunity and diagnosis are guaranteed in the next few years. Therefore, the present review will update the current knowledge and future trends of research on PCV-3.",2018 Dec 12,"['Klaumann, Francini', 'Correa-Fiz, Florencia', 'Franzo, Giovanni', 'Sibila, Marina', 'Núñez, José I.', 'Segalés, Joaquim']",Front Vet Sci,,,True
b28a8c489742fd2227e6e4049d777febfd4051cc,PMC,Design of Peptide-Based Nanovaccines Targeting Leading Antigens From Gynecological Cancers to Induce HLA-A2.1 Restricted CD8(+) T Cell Responses,http://dx.doi.org/10.3389/fimmu.2018.02968,PMC6315164,30631324,CC BY,"Gynecological cancers are a leading cause of mortality in women. CD8(+) T cell immunity largely correlates with enhanced survival, whereas inflammation is associated with poor prognosis. Previous studies have shown polystyrene nanoparticles (PSNPs) are biocompatible, do not induce inflammation and when used as vaccine carriers for model peptides induce CD8(+) T cell responses. Herein we test the immunogenicity of 24 different peptides, from three leading vaccine target proteins in gynecological cancers: the E7 protein of human papilloma virus (HPV); Wilms Tumor antigen 1 (WT1) and survivin (SV), in PSNP conjugate vaccines. Of relevance to vaccine development was the finding that a minimal CD8(+) T cell peptide epitope from HPV was not able to induce HLA-A2.1 specific CD8(+) T cell responses in transgenic humanized mice using conventional adjuvants such as CpG, but was nevertheless able to generate strong immunity when delivered as part of a specific longer peptide conjugated to PSNPs vaccines. Conversely, in most cases, when the minimal CD8(+) T cell epitopes were able to induce immune responses (with WT1 or SV super agonists) in CpG, they also induced responses when conjugated to PSNPs. In this case, extending the sequence around the CD8(+) T cell epitope, using the natural protein context, or engineering linker sequences proposed to enhance antigen processing, had minimal effects in enhancing or changing the cross-reactivity pattern induced by the super agonists. Nanoparticle approaches, such as PSNPs, therefore may offer an alternative vaccination strategy when conventional adjuvants are unable to elicit the desired CD8(+) T cell specificity. The findings herein also offer sequence specific insights into peptide vaccine design for nanoparticle-based vaccine carriers.",2018 Dec 21,"['Xiang, Sue D.', 'Wilson, Kirsty L.', 'Goubier, Anne', 'Heyerick, Arne', 'Plebanski, Magdalena']",Front Immunol,,,True
a4f120c79ea75052176f2c3d6a351485862a6ca8,PMC,Neutralizing Monoclonal Antibodies as Promising Therapeutics against Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.3390/v10120680,PMC6315345,30513619,CC BY,"Since emerging in 2012, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has been a global public health threat with a high fatality rate and worldwide distribution. There are no approved vaccines or therapies for MERS until now. Passive immunotherapy with neutralizing monoclonal antibodies (mAbs) is an effective prophylactic and therapeutic reagent against emerging viruses. In this article, we review current advances in neutralizing mAbs against MERS-CoV. The receptor-binding domain (RBD) in the spike protein of MERS-CoV is a major target, and mouse, camel, or human-derived neutralizing mAbs targeting RBD have been developed. A major problem with neutralizing mAb therapy is mutant escape under selective pressure, which can be solved by combination of neutralizing mAbs targeting different epitopes. Neutralizing mAbs are currently under preclinical evaluation, and they are promising candidate therapeutic agents against MERS-CoV infection.",2018 Nov 30,"['Han, Hui-Ju', 'Liu, Jian-Wei', 'Yu, Hao', 'Yu, Xue-Jie']",Viruses,,,True
eccc33ccb0e981e31f4d18d258274a7dae3ca2bc,PMC,Identification of Diaryl-Quinoline Compounds as Entry Inhibitors of Ebola Virus,http://dx.doi.org/10.3390/v10120678,PMC6315506,30513600,CC BY,"Ebola virus is the causative agent of Ebola virus disease in humans. The lethality of Ebola virus infection is about 50%, supporting the urgent need to develop anti-Ebola drugs. Glycoprotein (GP) is the only surface protein of the Ebola virus, which is functionally critical for the virus to attach and enter the host cells, and is a promising target for anti-Ebola virus drug development. In this study, using the recombinant HIV-1/Ebola pseudovirus platform we previously established, we evaluated a small molecule library containing various quinoline compounds for anti-Ebola virus entry inhibitors. Some of the quinoline compounds specifically inhibited the entry of the Ebola virus. Among them, compound SYL1712 was the most potent Ebola virus entry inhibitor with an IC(50) of ~1 μM. The binding of SYL1712 to the vial glycoprotein was computationally modeled and was predicted to interact with specific residues of GP. We used the time of the addition assay to show that compound SYL1712 blocks Ebola GP-mediated entry. Finally, consistent with being an Ebola virus entry inhibitor, compound SYL1712 inhibited infectious Ebola virus replication in tissue culture under biosafety level 4 containment, with an IC(50) of 2 μM. In conclusion, we identified several related molecules with a diaryl-quinoline scaffold as potential anti-EBOV entry inhibitors, which can be further optimized for anti-Ebola drug development.",2018 Nov 30,"['Cui, Qinghua', 'Cheng, Han', 'Xiong, Rui', 'Zhang, Gang', 'Du, Ruikun', 'Anantpadma, Manu', 'Davey, Robert A.', 'Rong, Lijun']",Viruses,,,True
9e2a08cf92331730a08aa78f309e7540dcfa18aa,PMC,Identification of Diaryl-Quinoline Compounds as Entry Inhibitors of Ebola Virus,http://dx.doi.org/10.3390/v10120678,PMC6315506,30513600,CC BY,"Ebola virus is the causative agent of Ebola virus disease in humans. The lethality of Ebola virus infection is about 50%, supporting the urgent need to develop anti-Ebola drugs. Glycoprotein (GP) is the only surface protein of the Ebola virus, which is functionally critical for the virus to attach and enter the host cells, and is a promising target for anti-Ebola virus drug development. In this study, using the recombinant HIV-1/Ebola pseudovirus platform we previously established, we evaluated a small molecule library containing various quinoline compounds for anti-Ebola virus entry inhibitors. Some of the quinoline compounds specifically inhibited the entry of the Ebola virus. Among them, compound SYL1712 was the most potent Ebola virus entry inhibitor with an IC(50) of ~1 μM. The binding of SYL1712 to the vial glycoprotein was computationally modeled and was predicted to interact with specific residues of GP. We used the time of the addition assay to show that compound SYL1712 blocks Ebola GP-mediated entry. Finally, consistent with being an Ebola virus entry inhibitor, compound SYL1712 inhibited infectious Ebola virus replication in tissue culture under biosafety level 4 containment, with an IC(50) of 2 μM. In conclusion, we identified several related molecules with a diaryl-quinoline scaffold as potential anti-EBOV entry inhibitors, which can be further optimized for anti-Ebola drug development.",2018 Nov 30,"['Cui, Qinghua', 'Cheng, Han', 'Xiong, Rui', 'Zhang, Gang', 'Du, Ruikun', 'Anantpadma, Manu', 'Davey, Robert A.', 'Rong, Lijun']",Viruses,,,False
8cd645b337ac36abbd467302eb73b4ae086e60ac,PMC,Methanolic Extract of Rhizoma Coptidis Inhibits the Early Viral Entry Steps of Hepatitis C Virus Infection,http://dx.doi.org/10.3390/v10120669,PMC6315547,30486350,CC BY,"Hepatitis C Virus (HCV) remains an important public health threat with approximately 170 million carriers worldwide who are at risk of developing hepatitis C-associated end-stage liver diseases. Despite improvement of HCV treatment using the novel direct-acting antivirals (DAAs) targeting viral replication, there is a lack of prophylactic measures for protection against HCV infection. Identifying novel antivirals such as those that target viral entry could help broaden the therapeutic arsenal against HCV. Herein, we investigated the anti-HCV activity of the methanolic extract from Rhizoma coptidis (RC), a widely used traditional Chinese medicine documented by the WHO and experimentally reported to possess several pharmacological functions including antiviral effects. Using the cell culture-derived HCV system, we demonstrated that RC dose-dependently inhibited HCV infection of Huh-7.5 cells at non-cytotoxic concentrations. In particular, RC blocked HCV attachment and entry/fusion into the host cells without exerting any significant effect on the cell-free viral particles or modulating key host cell entry factors to HCV. Moreover, RC robustly suppressed HCV pseudoparticles infection of Huh-7.5 cells and impeded infection by several HCV genotypes. Collectively, our results identified RC as a potent antagonist to HCV entry with potential pan-genotypic properties, which deserves further evaluation for use as an anti-HCV agent.",2018 Nov 27,"['Hung, Ting-Chun', 'Jassey, Alagie', 'Lin, Chien-Ju', 'Liu, Ching-Hsuan', 'Lin, Chun-Ching', 'Yen, Ming-Hong', 'Lin, Liang-Tzung']",Viruses,,,True
0f38c2681e9e286de25759866e018b1c4a2a88c6,PMC,Methanolic Extract of Rhizoma Coptidis Inhibits the Early Viral Entry Steps of Hepatitis C Virus Infection,http://dx.doi.org/10.3390/v10120669,PMC6315547,30486350,CC BY,"Hepatitis C Virus (HCV) remains an important public health threat with approximately 170 million carriers worldwide who are at risk of developing hepatitis C-associated end-stage liver diseases. Despite improvement of HCV treatment using the novel direct-acting antivirals (DAAs) targeting viral replication, there is a lack of prophylactic measures for protection against HCV infection. Identifying novel antivirals such as those that target viral entry could help broaden the therapeutic arsenal against HCV. Herein, we investigated the anti-HCV activity of the methanolic extract from Rhizoma coptidis (RC), a widely used traditional Chinese medicine documented by the WHO and experimentally reported to possess several pharmacological functions including antiviral effects. Using the cell culture-derived HCV system, we demonstrated that RC dose-dependently inhibited HCV infection of Huh-7.5 cells at non-cytotoxic concentrations. In particular, RC blocked HCV attachment and entry/fusion into the host cells without exerting any significant effect on the cell-free viral particles or modulating key host cell entry factors to HCV. Moreover, RC robustly suppressed HCV pseudoparticles infection of Huh-7.5 cells and impeded infection by several HCV genotypes. Collectively, our results identified RC as a potent antagonist to HCV entry with potential pan-genotypic properties, which deserves further evaluation for use as an anti-HCV agent.",2018 Nov 27,"['Hung, Ting-Chun', 'Jassey, Alagie', 'Lin, Chien-Ju', 'Liu, Ching-Hsuan', 'Lin, Chun-Ching', 'Yen, Ming-Hong', 'Lin, Liang-Tzung']",Viruses,,,False
d50946bee04acb73e91b3735ccb661a278b86685,PMC,Viral-Mediated mRNA Degradation for Pathogenesis,http://dx.doi.org/10.3390/biomedicines6040111,PMC6315618,30501096,CC BY,"Cellular RNA decay machinery plays a vital role in regulating gene expression by altering the stability of mRNAs in response to external stresses, including viral infection. In the primary infection, viruses often conquer the host cell’s antiviral immune response by controlling the inherently cellular mRNA degradation machinery to facilitate viral gene expression and establish a successful infection. This review summarizes the current knowledge about the diverse strategies of viral-mediated regulatory RNA shutoff for pathogenesis, and particularly sheds a light on the mechanisms that viruses evolve to elude immune surveillance during infection.",2018 Nov 29,"['Du, Shujuan', 'Liu, Xiaoqing', 'Cai, Qiliang']",Biomedicines,,,True
551c5105a50ea1d7d52d13424441d1788f67bc91,PMC,Comparison of Perceived and Observed Hand Hygiene Compliance in Healthcare Workers in MERS-CoV Endemic Regions,http://dx.doi.org/10.3390/healthcare6040122,PMC6315729,30301272,CC BY,"This study investigated healthcare workers’ perceptions of hand hygiene practices by comparing personal reports, as assessed by questionnaires, to direct observations of the workers’ hand hygiene practices. The study employed a cross-sectional research design. Observations were made using a 16-item checklist, based on three sources: Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), and Boyce and Pittet’s guidelines of hand hygiene. The checklist was used for both direct-observation and self-reported data collection purposes. Pearson correlation and Multivariate Analysis of Covariance (MANCOVA) were utilized to statistically determine the relationship between healthcare workers’ reports of hand hygiene practices and observed hand hygiene behaviors. The study was conducted in the outpatient examination rooms and emergency departments of three types of hospitals in the Eastern region of Saudi Arabia where Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic and is observed in routine cases and outbreaks. The total sample size included 87 physicians and nurses recruited while on duty during the scheduled observation periods, with each healthcare worker being observed during individual medical examinations with at least three patients. No statistically significant correlations between the healthcare workers’ perceptions of hand hygiene practices and healthcare workers’ actual behaviors were evident. Based on the self-report questionnaires, significant differences were found between physicians’ and nurses’ hand hygiene practices reports. Healthcare workers clearly understand the importance of careful hand hygiene practices, but based on researchers’ observations, the medical personnel failed to properly implement protocol-driven hand hygiene applications. However, the significant differences between physicians’ and nurses’ self-reports suggest further inquiry is needed to fully explore these discrepancies.",2018 Oct 7,"['Alshammari, Modhi', 'Reynolds, Kelly A.', 'Verhougstraete, Marc', 'O’Rourke, Mary Kay']",Healthcare (Basel),,,True
6b3ebb32594707253e29179e7616236fdff6f362,PMC,One Health (r)Evolution: Learning from the Past to Build a New Future,http://dx.doi.org/10.3390/v10120725,PMC6315842,30567338,CC BY,"The One Health concept recognizes that the health of human beings, animals, plants and the environment is interconnected and interdependent. This idea has been shaped over the centuries and has gained momentum and traction as anatomy, physiology, microbiology and other disciplines have substantiated earlier theories. Here we recall major historical milestones which have contributed to shaping the One Health concept as it is today, and discuss the past and future drivers in view of future challenges in an evolving scenario.",2018 Dec 18,"['Capua, Ilaria', 'Cattoli, Giovanni']",Viruses,,,True
c7ddb36588a83decb4c6bcd033f9a0b208e66973,PMC,The Amino-Terminal Region of Hepatitis E Virus ORF1 Containing a Methyltransferase (Met) and a Papain-Like Cysteine Protease (PCP) Domain Counteracts Type I Interferon Response,http://dx.doi.org/10.3390/v10120726,PMC6315852,30567349,CC BY,"Hepatitis E virus (HEV) is responsible for large waterborne epidemics of hepatitis in endemic countries and is an emerging zoonotic pathogen worldwide. In endemic regions, HEV-1 or HEV-2 genotypes are frequently associated with fulminant hepatitis in pregnant women, while with zoonotic HEV (HEV-3 and HEV-4), chronic cases of hepatitis and severe neurological disorders are reported. Hence, it is important to characterize the interactions between HEV and its host. Here, we investigated the ability of the nonstructural polyprotein encoded by the first open reading frame (ORF1) of HEV to modulate the host early antiviral response and, in particular, the type I interferon (IFN-I) system. We found that the amino-terminal region of HEV-3 ORF1 (MetYPCP), containing a putative methyltransferase (Met) and a papain-like cysteine protease (PCP) functional domain, inhibited IFN-stimulated response element (ISRE) promoter activation and the expression of several IFN-stimulated genes (ISGs) in response to IFN-I. We showed that the MetYPCP domain interfered with the Janus kinase (JAK)/signal transducer and activator of the transcription protein (STAT) signalling pathway by inhibiting STAT1 nuclear translocation and phosphorylation after IFN-I treatment. In contrast, MetYPCP had no effect on STAT2 phosphorylation and a limited impact on the activation of the JAK/STAT pathway after IFN-II stimulation. This inhibitory function seemed to be genotype-dependent, as MetYPCP from HEV-1 had no significant effect on the JAK/STAT pathway. Overall, this study provides evidence that the predicted MetYPCP domain of HEV ORF1 antagonises STAT1 activation to modulate the IFN response.",2018 Dec 18,"['Bagdassarian, Eugénie', 'Doceul, Virginie', 'Pellerin, Marie', 'Demange, Antonin', 'Meyer, Léa', 'Jouvenet, Nolwenn', 'Pavio, Nicole']",Viruses,,,True
87ebc8d21e46aeef0eaa3db05d3c4611a547d7f2,PMC,The Amino-Terminal Region of Hepatitis E Virus ORF1 Containing a Methyltransferase (Met) and a Papain-Like Cysteine Protease (PCP) Domain Counteracts Type I Interferon Response,http://dx.doi.org/10.3390/v10120726,PMC6315852,30567349,CC BY,"Hepatitis E virus (HEV) is responsible for large waterborne epidemics of hepatitis in endemic countries and is an emerging zoonotic pathogen worldwide. In endemic regions, HEV-1 or HEV-2 genotypes are frequently associated with fulminant hepatitis in pregnant women, while with zoonotic HEV (HEV-3 and HEV-4), chronic cases of hepatitis and severe neurological disorders are reported. Hence, it is important to characterize the interactions between HEV and its host. Here, we investigated the ability of the nonstructural polyprotein encoded by the first open reading frame (ORF1) of HEV to modulate the host early antiviral response and, in particular, the type I interferon (IFN-I) system. We found that the amino-terminal region of HEV-3 ORF1 (MetYPCP), containing a putative methyltransferase (Met) and a papain-like cysteine protease (PCP) functional domain, inhibited IFN-stimulated response element (ISRE) promoter activation and the expression of several IFN-stimulated genes (ISGs) in response to IFN-I. We showed that the MetYPCP domain interfered with the Janus kinase (JAK)/signal transducer and activator of the transcription protein (STAT) signalling pathway by inhibiting STAT1 nuclear translocation and phosphorylation after IFN-I treatment. In contrast, MetYPCP had no effect on STAT2 phosphorylation and a limited impact on the activation of the JAK/STAT pathway after IFN-II stimulation. This inhibitory function seemed to be genotype-dependent, as MetYPCP from HEV-1 had no significant effect on the JAK/STAT pathway. Overall, this study provides evidence that the predicted MetYPCP domain of HEV ORF1 antagonises STAT1 activation to modulate the IFN response.",2018 Dec 18,"['Bagdassarian, Eugénie', 'Doceul, Virginie', 'Pellerin, Marie', 'Demange, Antonin', 'Meyer, Léa', 'Jouvenet, Nolwenn', 'Pavio, Nicole']",Viruses,,,False
069b422b624f7d6bb46b8381030550a88a3b30dd,PMC,"Alston Virus, a Novel Paramyxovirus Isolated from Bats Causes Upper Respiratory Tract Infection in Experimentally Challenged Ferrets",http://dx.doi.org/10.3390/v10120675,PMC6315912,30487438,CC BY,"Multiple viruses with zoonotic potential have been isolated from bats globally. Here we describe the isolation and characterization of a novel paramyxovirus, Alston virus (AlsPV), isolated from urine collected from an Australian pteropid bat colony in Alstonville, New South Wales. Characterization of AlsPV by whole-genome sequencing and analyzing antigenic relatedness revealed it is a rubulavirus that is closely related to parainfluenza virus 5 (PIV5). Intranasal exposure of mice to AlsPV resulted in no clinical signs of disease, although viral RNA was detected in the olfactory bulbs of two mice at 21 days post exposure. Oronasal challenge of ferrets resulted in subclinical upper respiratory tract infection, viral shedding in respiratory secretions, and detection of viral antigen in the olfactory bulb of the brain. These results imply that AlsPV may be similar to PIV5 in its ability to infect multiple mammalian host species. This isolation of a novel paramyxovirus with the potential to transmit from bats to other mammalian species reinforces the importance of continued surveillance of bats as a source of emerging viruses.",2018 Nov 28,"['Johnson, Rebecca I.', 'Tachedjian, Mary', 'Rowe, Brenton', 'Clayton, Bronwyn A.', 'Layton, Rachel', 'Bergfeld, Jemma', 'Wang, Lin-Fa', 'Marsh, Glenn A.']",Viruses,,,True
f6a0c9664bdc94f48f0f2deed4bd3c4dbc1f44c5,PMC,"Alston Virus, a Novel Paramyxovirus Isolated from Bats Causes Upper Respiratory Tract Infection in Experimentally Challenged Ferrets",http://dx.doi.org/10.3390/v10120675,PMC6315912,30487438,CC BY,"Multiple viruses with zoonotic potential have been isolated from bats globally. Here we describe the isolation and characterization of a novel paramyxovirus, Alston virus (AlsPV), isolated from urine collected from an Australian pteropid bat colony in Alstonville, New South Wales. Characterization of AlsPV by whole-genome sequencing and analyzing antigenic relatedness revealed it is a rubulavirus that is closely related to parainfluenza virus 5 (PIV5). Intranasal exposure of mice to AlsPV resulted in no clinical signs of disease, although viral RNA was detected in the olfactory bulbs of two mice at 21 days post exposure. Oronasal challenge of ferrets resulted in subclinical upper respiratory tract infection, viral shedding in respiratory secretions, and detection of viral antigen in the olfactory bulb of the brain. These results imply that AlsPV may be similar to PIV5 in its ability to infect multiple mammalian host species. This isolation of a novel paramyxovirus with the potential to transmit from bats to other mammalian species reinforces the importance of continued surveillance of bats as a source of emerging viruses.",2018 Nov 28,"['Johnson, Rebecca I.', 'Tachedjian, Mary', 'Rowe, Brenton', 'Clayton, Bronwyn A.', 'Layton, Rachel', 'Bergfeld, Jemma', 'Wang, Lin-Fa', 'Marsh, Glenn A.']",Viruses,,,False
7c92eb9f2f7fd93501102671ee6595e0b157383d,PMC,The Structure-To-Function Relationships of Gammaherpesvirus-Encoded Long Non-Coding RNAs and Their Contributions to Viral Pathogenesis,http://dx.doi.org/10.3390/ncrna4040024,PMC6315926,30261651,CC BY,"Advances in next-generation sequencing have facilitated the discovery of a multitude of long non-coding RNAs (lncRNAs) with pleiotropic functions in cellular processes, disease, and viral pathogenesis. It came as no surprise when viruses were also revealed to transcribe their own lncRNAs. Among them, gammaherpesviruses, one of the three subfamilies of the Herpesviridae, code their largest number. These structurally and functionally intricate non-coding (nc) transcripts modulate cellular and viral gene expression to maintain viral latency or prompt lytic reactivation. These lncRNAs allow for the virus to escape cytosolic surveillance, sequester, and re-localize essential cellular factors and modulate the cell cycle and proliferation. Some viral lncRNAs act as “messenger molecules”, transferring information about viral infection to neighboring cells. This broad range of lncRNA functions is achieved through lncRNA structure-mediated interactions with effector molecules of viral and host origin, including other RNAs, proteins and DNAs. In this review, we discuss examples of gammaherpesvirus-encoded lncRNAs, emphasize their unique structural attributes, and link them to viral life cycle, pathogenesis, and disease progression. We will address their potential as novel targets for drug discovery and propose future directions to explore lncRNA structure and function relationship.",2018 Sep 26,"['Chavez-Calvillo, Gabriela', 'Martin, Sarah', 'Hamm, Chad', 'Sztuba-Solinska, Joanna']",Noncoding RNA,,,True
e620067ec156a1fc9e5b28aaf66b38dd08815df8,PMC,Clinical and Molecular Features of Feline Foamy Virus and Feline Leukemia Virus Co-Infection in Naturally-Infected Cats,http://dx.doi.org/10.3390/v10120702,PMC6315984,30544924,CC BY,"Feline foamy virus (FFV) and feline leukemia virus (FeLV) belong to the Retroviridae family. While disease has not been reported for FFV infection, FeLV infection can cause anemia and immunosuppression (progressive infection). Co-infection with FFV/FeLV allows evaluation of the pathogenic potential and epidemiology of FFV infection in cats with FeLV pathology. Blood and buccal swab samples from 81 cats were collected in Rio de Janeiro. Plasma was serologically tested for FeLV. DNA extracted from peripheral blood mononuclear cells and buccal swabs was used to PCR detect FFV and FeLV. A qPCR was developed to detect and measure FFV proviral loads (pVLs) in cats. FeLV qPCR was performed using previous methods. The median log10 pVL of FFV mono-infected individuals was lower than found in FFV/FeLV co-infected cats in buccal swabs (p = 0.003). We found 78% of cats had detectable buccal FFV DNA in FFV mono-infected and FFV co-infected FeLV-progressive cats, while in FeLV-regressive cats (those without signs of disease) 22% of cats had detectable buccal FFV DNA (p = 0.004). Our results suggest that regressive FeLV infection may reduce FFV saliva transmission, the main mode of FV transmission. We did not find evidence of differences in pathogenicity in FFV mono- and -dually infected cats. In summary, we show that FVs may interact with FeLV within the same host. Our study supports the utility of cats naturally co-infected with retroviruses as a model to investigate the impact of FV on immunocompromised mammalian hosts.",2018 Dec 11,"['Cavalcante, Liliane T. F.', 'Muniz, Cláudia P.', 'Jia, Hongwei', 'Augusto, Anderson M.', 'Troccoli, Fernando', 'Medeiros, Sheila de O.', 'Dias, Carlos G. A.', 'Switzer, William M.', 'Soares, Marcelo A.', 'Santos, André F.']",Viruses,,,True
023b805a96c852619186f55af4bbbdd5f9fa8156,PMC,Gene Variations in Cis-Acting Elements between the Taiwan and Prototype Strains of Porcine Epidemic Diarrhea Virus Alter Viral Gene Expression,http://dx.doi.org/10.3390/genes9120591,PMC6316102,30501108,CC BY,"In 2013, the outbreak of porcine epidemic diarrhea (PED) in Taiwan caused serious economic losses. In this study, we examined whether the variations of the cis-acting elements between the porcine epidemic diarrhea virus (PEDV) Taiwan (TW) strain and the prototype strain CV777 alter gene expression. For this aim, we analyzed the variations of the cis-acting elements in the 5′ and 3′ untranslated regions (UTRs) between the PEDV TW, CV777, and other reference strains. We also determined the previously unidentified transcription regulatory sequence (TRS), a sequence motif required for coronavirus transcription, and found that a nucleotide deletion in the TW strain, in comparison with CV777 strain, immediately downstream of the leader core sequence alters the identity between the leader TRS and the body TRS. Functional analyses using coronavirus defective interfering (DI) RNA revealed that such variations in cis-acting elements for the TW strain compared with the CV777 strain have an influence on the efficiency of gene expression. The current data show for the first time the evolution of PEDV in terms of cis-acting elements and their effects on gene expression, and thus may contribute to our understanding of recent PED outbreaks worldwide.",2018 Nov 29,"['Tsai, Tsung-Lin', 'Su, Chen-Chang', 'Hsieh, Ching-Chi', 'Lin, Chao-Nan', 'Chang, Hui-Wen', 'Lo, Chen-Yu', 'Lin, Ching-Houng', 'Wu, Hung-Yi']",Genes (Basel),,,True
ad2f0d75547203aeb3bea0353087830d27f791df,PMC,Gene Variations in Cis-Acting Elements between the Taiwan and Prototype Strains of Porcine Epidemic Diarrhea Virus Alter Viral Gene Expression,http://dx.doi.org/10.3390/genes9120591,PMC6316102,30501108,CC BY,"In 2013, the outbreak of porcine epidemic diarrhea (PED) in Taiwan caused serious economic losses. In this study, we examined whether the variations of the cis-acting elements between the porcine epidemic diarrhea virus (PEDV) Taiwan (TW) strain and the prototype strain CV777 alter gene expression. For this aim, we analyzed the variations of the cis-acting elements in the 5′ and 3′ untranslated regions (UTRs) between the PEDV TW, CV777, and other reference strains. We also determined the previously unidentified transcription regulatory sequence (TRS), a sequence motif required for coronavirus transcription, and found that a nucleotide deletion in the TW strain, in comparison with CV777 strain, immediately downstream of the leader core sequence alters the identity between the leader TRS and the body TRS. Functional analyses using coronavirus defective interfering (DI) RNA revealed that such variations in cis-acting elements for the TW strain compared with the CV777 strain have an influence on the efficiency of gene expression. The current data show for the first time the evolution of PEDV in terms of cis-acting elements and their effects on gene expression, and thus may contribute to our understanding of recent PED outbreaks worldwide.",2018 Nov 29,"['Tsai, Tsung-Lin', 'Su, Chen-Chang', 'Hsieh, Ching-Chi', 'Lin, Chao-Nan', 'Chang, Hui-Wen', 'Lo, Chen-Yu', 'Lin, Ching-Houng', 'Wu, Hung-Yi']",Genes (Basel),,,False
f176cd025d08014cfb69f9d2b28e92b19a1a7522,PMC,Development of Small-Molecule MERS-CoV Inhibitors,http://dx.doi.org/10.3390/v10120721,PMC6316138,30562987,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) with potential to cause global pandemics remains a threat to the public health, security, and economy. In this review, we focus on advances in the research and development of small-molecule MERS-CoV inhibitors targeting different stages of the MERS-CoV life cycle, aiming to prevent or treat MERS-CoV infection.",2018 Dec 17,"['Liang, Ruiying', 'Wang, Lili', 'Zhang, Naru', 'Deng, Xiaoqian', 'Su, Meng', 'Su, Yudan', 'Hu, Lanfang', 'He, Chen', 'Ying, Tianlei', 'Jiang, Shibo', 'Yu, Fei']",Viruses,,,True
ba24b8b4f656dd857e9b151c22c0619b88c63f65,PMC,Recent Advances in AIV Biosensors Composed of Nanobio Hybrid Material,http://dx.doi.org/10.3390/mi9120651,PMC6316213,30544883,CC BY,"Since the beginning of the 2000s, globalization has accelerated because of the development of transportation systems that allow for human and material exchanges throughout the world. However, this globalization has brought with it the rise of various pathogenic viral agents, such as Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Zika virus, and Dengue virus. In particular, avian influenza virus (AIV) is highly infectious and causes economic, health, ethnical, and social problems to human beings, which has necessitated the development of an ultrasensitive and selective rapid-detection system of AIV. To prevent the damage associated with the spread of AIV, early detection and adequate treatment of AIV is key. There are traditional techniques that have been used to detect AIV in chickens, ducks, humans, and other living organisms. However, the development of a technique that allows for the more rapid diagnosis of AIV is still necessary. To achieve this goal, the present article reviews the use of an AIV biosensor employing nanobio hybrid materials to enhance the sensitivity and selectivity of the technique while also reducing the detection time and high-throughput process time. This review mainly focused on four techniques: the electrochemical detection system, electrical detection method, optical detection methods based on localized surface plasmon resonance, and fluorescence.",2018 Dec 9,"['Lee, Taek', 'Ahn, Jae-Hyuk', 'Park, Sun Yong', 'Kim, Ga-Hyeon', 'Kim, Jeonghyun', 'Kim, Tae-Hyung', 'Nam, Inho', 'Park, Chulhwan', 'Lee, Min-Ho']",Micromachines (Basel),,,True
70bf84100e6157f3815acca7b5120131c0f8cf4e,PMC,Small Animal Models of Respiratory Viral Infection Related to Asthma,http://dx.doi.org/10.3390/v10120682,PMC6316391,30513770,CC BY,Respiratory viral infections are strongly associated with asthma exacerbations. Rhinovirus is most frequently-detected pathogen; followed by respiratory syncytial virus; metapneumovirus; parainfluenza virus; enterovirus and coronavirus. In addition; viral infection; in combination with genetics; allergen exposure; microbiome and other pathogens; may play a role in asthma development. In particular; asthma development has been linked to wheezing-associated respiratory viral infections in early life. To understand underlying mechanisms of viral-induced airways disease; investigators have studied respiratory viral infections in small animals. This report reviews animal models of human respiratory viral infection employing mice; rats; guinea pigs; hamsters and ferrets. Investigators have modeled asthma exacerbations by infecting mice with allergic airways disease. Asthma development has been modeled by administration of virus to immature animals. Small animal models of respiratory viral infection will identify cell and molecular targets for the treatment of asthma.,2018 Dec 1,"['Han, Mingyuan', 'Rajput, Charu', 'Ishikawa, Tomoko', 'Jarman, Caitlin R.', 'Lee, Julie', 'Hershenson, Marc B.']",Viruses,,,True
5ab81ec18627585be0e852bdd61472e98f531701,PMC,Simultaneous Detection of Different Zika Virus Lineages via Molecular Computation in a Point-of-Care Assay,http://dx.doi.org/10.3390/v10120714,PMC6316447,30558136,CC BY,"We have developed a generalizable “smart molecular diagnostic” capable of accurate point-of-care (POC) detection of variable nucleic acid targets. Our isothermal assay relies on multiplex execution of four loop-mediated isothermal amplification reactions, with primers that are degenerate and redundant, thereby increasing the breadth of targets while reducing the probability of amplification failure. An easy-to-read visual answer is computed directly by a multi-input Boolean OR logic gate (gate output is true if either one or more gate inputs is true) signal transducer that uses degenerate strand exchange probes to assess any combination of amplicons. We demonstrate our methodology by using the same assay to detect divergent Asian and African lineages of the evolving Zika virus (ZIKV), while maintaining selectivity against non-target viruses. Direct analysis of biological specimens proved possible, with crudely macerated ZIKV-infected Aedes aegypti mosquitoes being identified with 100% specificity and sensitivity. The ease-of-use with minimal instrumentation, broad programmability, and built-in fail-safe reliability make our smart molecular diagnostic attractive for POC use.",2018 Dec 14,"['Bhadra, Sanchita', 'Saldaña, Miguel A.', 'Han, Hannah Grace', 'Hughes, Grant L.', 'Ellington, Andrew D.']",Viruses,,,True
3b7e06a340e084847e969e188f5d2a7789af2f25,PMC,Proteomics of Bronchoalveolar Lavage Fluid Reveals a Lung Oxidative Stress Response in Murine Herpesvirus-68 Infection,http://dx.doi.org/10.3390/v10120670,PMC6316452,30486363,CC BY,"Murine herpesvirus-68 (MHV-68) productively infects mouse lungs, exhibiting a complex pathology characteristic of both acute viral infections and chronic respiratory diseases. We sought to discover proteins differentially expressed in bronchoalveolar lavage (BAL) from mice infected with MHV-68. Mice were infected intranasally with MHV-68. After nine days, as the lytic phase of infection resolved, differential BAL proteins were identified by two-dimensional (2D) electrophoresis and mass spectrometry. Of 23 unique proteins, acute phase proteins, vitamin A transport, and oxidative stress response factors Pdx6 and EC-SOD (Sod3) were enriched. Correspondingly, iNOS2 was induced in lung tissue by seven days post-infection. Oxidative stress was partly a direct result of MHV-68 infection, as reactive oxygen species (ROS) were induced in cultured murine NIH3T3 fibroblasts and human lung A549 cells infected with MHV-68. Finally, mice infected with a recombinant MHV-68 co-expressing inflammatory cytokine murine interleukin 6 (IL6) showed exacerbated oxidative stress and soluble type I collagen characteristic of tissue recovery. Thus, oxidative stress appears to be a salient feature of MHV-68 pathogenesis, in part caused by lytic replication of the virus and IL6. Proteins and small molecules in lung oxidative stress networks therefore may provide new therapeutic targets to ameliorate respiratory virus infections.",2018 Nov 27,"['Bortz, Eric', 'Wu, Ting-Ting', 'Patel, Parthive', 'Whitelegge, Julian P.', 'Sun, Ren']",Viruses,,,True
45d3b6128146d7df335e96fb8257644f0a5fca14,PMC,Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling,http://dx.doi.org/10.3390/v10120716,PMC6316657,30558248,CC BY,"Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease. Retinoic acid-inducible gene-I (RIG-I) serves as an innate immune sensor and triggers antiviral responses upon recognizing viral infections including RSV. Since tripartite motif-containing protein 25 (TRIM25)-mediated K63-polyubiquitination is crucial for RIG-I activation, several viruses target initial RIG-I activation through ubiquitination. RSV NS1 and NS2 have been shown to interfere with RIG-I-mediated antiviral signaling. In this study, we explored the possibility that NS1 suppresses RIG-I-mediated antiviral signaling by targeting TRIM25. Ubiquitination of ectopically expressed RIG-I-2Cards domain was decreased by RSV infection, indicating that RSV possesses ability to inhibit TRIM25-mediated RIG-I ubiquitination. Similarly, ectopic expression of NS1 sufficiently suppressed TRIM25-mediated RIG-I ubiquitination. Furthermore, interaction between NS1 and TRIM25 was detected by a co-immunoprecipitation assay. Further biochemical assays showed that the SPRY domain of TRIM25, which is responsible for interaction with RIG-I, interacted sufficiently with NS1. Suppression of RIG-I ubiquitination by NS1 resulted in decreased interaction between RIG-I and its downstream molecule, MAVS. The suppressive effect of NS1 on RIG-I signaling could be abrogated by overexpression of TRIM25. Collectively, this study suggests that RSV NS1 interacts with TRIM25 and interferes with RIG-I ubiquitination to suppress type-I interferon signaling.",2018 Dec 14,"['Ban, Junsu', 'Lee, Na-Rae', 'Lee, Noh-Jin', 'Lee, Jong Kil', 'Quan, Fu-Shi', 'Inn, Kyung-Soo']",Viruses,,,True
be5bddac1b08e3f6c757bdbd6564255e6ee96f4a,PMC,SARS-Like Coronavirus WIV1-CoV Does Not Replicate in Egyptian Fruit Bats (Rousettus aegyptiacus),http://dx.doi.org/10.3390/v10120727,PMC6316779,30572566,CC BY,"Severe acute respiratory syndrome (SARS)-like WIV1-coronavirus (CoV) was first isolated from Rhinolophus sinicus bats and can use the human angiotensin converting enzyme 2 (ACE2) receptor. In the current study, we investigate the ability of WIV1-CoV to infect Rousettus aegyptiacus bats. No clinical signs were observed throughout the experiment. Furthermore, only four oropharyngeal swabs and two respiratory tissues, isolated on day 3 post inoculation, were found positive for viral RNA. Two out of twelve bats showed a modest increase in coronavirus specific antibodies post challenge. In conclusion, WIV1-CoV was unable to cause a robust infection in Rousettus aegyptiacus bats.",2018 Dec 19,"['van Doremalen, Neeltje', 'Schäfer, Alexandra', 'Menachery, Vineet D.', 'Letko, Michael', 'Bushmaker, Trenton', 'Fischer, Robert J.', 'Figueroa, Dania M.', 'Hanley, Patrick W.', 'Saturday, Greg', 'Baric, Ralph S.', 'Munster, Vincent J.']",Viruses,,,True
9dd88265053594d2736a884a8b972b6ae94218c5,PMC,CD8+ T Cells Responding to the Middle East Respiratory Syndrome Coronavirus Nucleocapsid Protein Delivered by Vaccinia Virus MVA in Mice,http://dx.doi.org/10.3390/v10120718,PMC6316859,30558354,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV), a novel infectious agent causing severe respiratory disease and death in humans, was first described in 2012. Antibodies directed against the MERS-CoV spike (S) protein are thought to play a major role in controlling MERS-CoV infection and in mediating vaccine-induced protective immunity. In contrast, relatively little is known about the role of T cell responses and the antigenic targets of MERS-CoV that are recognized by CD8+ T cells. In this study, the highly conserved MERS-CoV nucleocapsid (N) protein served as a target immunogen to elicit MERS-CoV-specific cellular immune responses. Modified Vaccinia virus Ankara (MVA), a safety-tested strain of vaccinia virus for preclinical and clinical vaccine research, was used for generating MVA-MERS-N expressing recombinant N protein. Overlapping peptides spanning the whole MERS-CoV N polypeptide were used to identify major histocompatibility complex class I/II-restricted T cell responses in BALB/c mice immunized with MVA-MERS-N. We have identified a H2-d restricted decamer peptide epitope in the MERS-N protein with CD8+ T cell antigenicity. The identification of this epitope, and the availability of the MVA-MERS-N candidate vaccine, will help to evaluate MERS-N-specific immune responses and the potential immune correlates of vaccine-mediated protection in the appropriate murine models of MERS-CoV infection.",2018 Dec 16,"['Veit, Svenja', 'Jany, Sylvia', 'Fux, Robert', 'Sutter, Gerd', 'Volz, Asisa']",Viruses,,,True
46d0095cb43747c3d9174dd29f9809c7cdc58684,PMC,CD8+ T Cells Responding to the Middle East Respiratory Syndrome Coronavirus Nucleocapsid Protein Delivered by Vaccinia Virus MVA in Mice,http://dx.doi.org/10.3390/v10120718,PMC6316859,30558354,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV), a novel infectious agent causing severe respiratory disease and death in humans, was first described in 2012. Antibodies directed against the MERS-CoV spike (S) protein are thought to play a major role in controlling MERS-CoV infection and in mediating vaccine-induced protective immunity. In contrast, relatively little is known about the role of T cell responses and the antigenic targets of MERS-CoV that are recognized by CD8+ T cells. In this study, the highly conserved MERS-CoV nucleocapsid (N) protein served as a target immunogen to elicit MERS-CoV-specific cellular immune responses. Modified Vaccinia virus Ankara (MVA), a safety-tested strain of vaccinia virus for preclinical and clinical vaccine research, was used for generating MVA-MERS-N expressing recombinant N protein. Overlapping peptides spanning the whole MERS-CoV N polypeptide were used to identify major histocompatibility complex class I/II-restricted T cell responses in BALB/c mice immunized with MVA-MERS-N. We have identified a H2-d restricted decamer peptide epitope in the MERS-N protein with CD8+ T cell antigenicity. The identification of this epitope, and the availability of the MVA-MERS-N candidate vaccine, will help to evaluate MERS-N-specific immune responses and the potential immune correlates of vaccine-mediated protection in the appropriate murine models of MERS-CoV infection.",2018 Dec 16,"['Veit, Svenja', 'Jany, Sylvia', 'Fux, Robert', 'Sutter, Gerd', 'Volz, Asisa']",Viruses,,,False
c6a56489ca7a8d317c3244f06f15cbbc95181fd4,PMC,Effects of Laser Texture Oxidation and High-Temperature Annealing of TiV Alloy Thin Films on Mechanical and Antibacterial Properties and Cytotoxicity,http://dx.doi.org/10.3390/ma11122495,PMC6316979,30544800,CC BY,"Titanium dioxide and vanadium oxides have been applied extensively in industrial and medical fields. The objective of this study was to develop various composite structures of titanium and vanadium oxide (Ti-V-O) coatings on pure titanium through high-temperature annealing and laser texturing oxidation, separately; additionally, surface morphologies, tribological and hydrophilic properties, and antibacterial and biocompatibility abilities of these Ti-V-O coatings were evaluated. TiV alloy thin films were deposited on pure titanium and then annealed to form Ti-V-O coatings through thermal oxidation and laser texturing oxidation. Ball-on-disc wear tests and contact angle tests were conducted to evaluate the tribological properties and wettability of the coatings, respectively. The antibacterial activity of the coatings was estimated by SYTO9 nucleic acid staining with Staphylococcus aureus (Gram-positive bacteria). The cell cytotoxicity of the coatings was analyzed following the ISO 10995-5:2009 standard with human skin fibroblast cells. The Ti-V-O coatings, subjected to annealing at 700 °C, demonstrated higher hardness (Hv 1171) and a lower friction coefficient (0.6). The highest hardness (Hv 2711) and the lowest friction coefficient (0.52) were obtained for the Ti-V-O after laser surface texturing oxidation at 100 kHz. The oxide coating obtained from 100 kHz laser texturing oxidation exhibited the lotus effect because of its systematic textured microstructures, and displayed superhydrophobic surface properties. Compared with the unannealed TiV coating, both the samples with high-temperature annealing and laser surface texturing oxidation had excellent antibacterial properties to Staphylococcus aureus. However, the Ti-V-O thin films exhibited notable cell cytotoxicity. Although the cell viability on Ti-V-O coatings were not ideal, this study confirmed improvement in surface hardness, tribology, and antibacterial performance in Ti-V-O coatings, which may have potential for use in biomedical tools, devices, and equipment.",2018 Dec 8,"['Chang, Yin-Yu', 'Zhang, Jia-Hao', 'Huang, Heng-Li']",Materials (Basel),,,True
e87256ec4a079c0792106d6503eb78af24aebdb4,PMC,Copper Alloy Touch Surfaces in Healthcare Facilities: An Effective Solution to Prevent Bacterial Spreading,http://dx.doi.org/10.3390/ma11122479,PMC6317222,30563265,CC BY,"In the healthcare environment, microorganisms’ cross-transmission between inanimate surfaces and patients or healthcare workers can lead to healthcare-associated infections. A recent interest has grown to create antimicrobial copper touch surfaces, in order to counteract microbial spread in the healthcare environment. For the first time, five French long-term care facilities were at 50% fitted with copper alloys door handles and handrails. Related to the environmental bacterial contamination, 1400 samples were carried out on copper and control surfaces over three years after copper installation. In addition, some copper door handles were taken from the different facilities, and their specific activity against methicillin-resistant S. aureus (MRSA) was tested in vitro. In comparison to control surfaces, copper door handles and handrails revealed significantly lower contamination levels. This difference was observed in the five long-term care facilities and it persists through the three years of the study. High and extreme levels of bacterial contamination were less frequent on copper surfaces. Although, the antibacterial activity of copper surfaces against MRSA was lowered after three years of regular use, it was still significant as compared to inert control surfaces. Therefore, copper containing surfaces are promising actors in the non-spreading of environmental bacterial contamination in healthcare facilities.",2018 Dec 6,"['Colin, Marius', 'Klingelschmitt, Flora', 'Charpentier, Emilie', 'Josse, Jérôme', 'Kanagaratnam, Lukshe', 'De Champs, Christophe', 'Gangloff, Sophie C.']",Materials (Basel),,,True
20306db30bbc6f1cc9cc3771a8defe841f6cce0f,PMC,Sharing health research data – the role of funders in improving the impact,http://dx.doi.org/10.12688/f1000research.16523.2,PMC6317492,30647910,CC BY,"Recent public health emergencies with outbreaks of influenza, Ebola and Zika revealed that the mechanisms for sharing research data are neither being used, or adequate for the purpose, particularly where data needs to be shared rapidly. A review of research papers, including completed clinical trials related to priority pathogens, found only 31% (98 out of 319 published papers, excluding case studies) provided access to all the data underlying the paper - 65% of these papers give no information on how to find or access the data. Only two clinical trials out of 58 on interventions for WHO priority pathogens provided any link in their registry entry to the background data. Interviews with researchers revealed a reluctance to share data included a lack of confidence in the utility of the data; an absence of academic-incentives for rapid dissemination that prevents subsequent publication and a disconnect between those who are collecting the data and those who wish to use it quickly.  The role of the funders of research needs to change to address this. Funders need to engage early with the researchers and related stakeholders to understand their concerns and work harder to define the more explicitly the benefits to all stakeholders.  Secondly, there needs to be a direct benefit to sharing data that is directly relevant to those people that collect and curate the data. Thirdly more work needs to be done to realise the intent of making data sharing resources more equitable, ethical and efficient.  Finally, a checklist of the issues that need to be addressed when designing new or revising existing data sharing resources should be created. This checklist would highlight the technical, cultural and ethical issues that need to be considered and point to examples of emerging good practice that can be used to address them.",2018 Dec 24,"['Terry, Robert F.', 'Littler, Katherine', 'Olliaro, Piero L.']",F1000Res,,,False
03774b269b5de5338590b1960b6468881604a3dc,PMC,Reining in the CD8+ T cell: Respiratory virus infection and PD-1-mediated T-cell impairment,http://dx.doi.org/10.1371/journal.ppat.1007387,PMC6317792,30605483,CC BY,,2019 Jan 3,"['Rogers, Meredith C.', 'Williams, John V.']",PLoS Pathog,,,True
c8a84384011fca6e1e24511d1b053eef4650fc04,PMC,Role of a fluid-phase PRR in fighting an intracellular pathogen: PTX3 in Shigella infection,http://dx.doi.org/10.1371/journal.ppat.1007469,PMC6317801,30532257,CC BY,"Shigella spp. are pathogenic bacteria that cause bacillary dysentery in humans by invading the colonic and rectal mucosa where they induce dramatic inflammation. Here, we have analyzed the role of the soluble PRR Pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity. Mice that had been intranasally infected with S. flexneri were rescued from death by treatment with recombinant PTX3. In vitro PTX3 exerts the antibacterial activity against Shigella, impairing epithelial cell invasion and contributing to the bactericidal activity of serum. PTX3 is produced upon LPS-TLR4 stimulation in accordance with the lipid A structure of Shigella. In the plasma of infected patients, the level of PTX3 amount only correlates strongly with symptom severity. These results signal PTX3 as a novel player in Shigella pathogenesis and its potential role in fighting shigellosis. Finally, we suggest that the plasma level of PTX3 in shigellosis patients could act as a biomarker for infection severity.",2018 Dec 7,"['Ciancarella, Valeria', 'Lembo-Fazio, Luigi', 'Paciello, Ida', 'Bruno, Anna-Karin', 'Jaillon, Sébastien', 'Berardi, Sara', 'Barbagallo, Marialuisa', 'Meron-Sudai, Shiri', 'Cohen, Dani', 'Molinaro, Antonio', 'Rossi, Giacomo', 'Garlanda, Cecilia', 'Bernardini, Maria Lina']",PLoS Pathog,,,True
b128c844332f52b348e2d35863b3d0cfcbc78bf9,PMC,The Airplane Cabin Microbiome,http://dx.doi.org/10.1007/s00248-018-1191-3,PMC6318343,29876609,CC BY,"Serving over three billion passengers annually, air travel serves as a conduit for infectious disease spread, including emerging infections and pandemics. Over two dozen cases of in-flight transmissions have been documented. To understand these risks, a characterization of the airplane cabin microbiome is necessary. Our study team collected 229 environmental samples on ten transcontinental US flights with subsequent 16S rRNA sequencing. We found that bacterial communities were largely derived from human skin and oral commensals, as well as environmental generalist bacteria. We identified clear signatures for air versus touch surface microbiome, but not for individual types of touch surfaces. We also found large flight-to-flight beta diversity variations with no distinguishing signatures of individual flights, rather a high between-flight diversity for all touch surfaces and particularly for air samples. There was no systematic pattern of microbial community change from pre- to post-flight. Our findings are similar to those of other recent studies of the microbiome of built environments. In summary, the airplane cabin microbiome has immense airplane to airplane variability. The vast majority of airplane-associated microbes are human commensals or non-pathogenic, and the results provide a baseline for non-crisis-level airplane microbiome conditions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00248-018-1191-3) contains supplementary material, which is available to authorized users.",2019 Jun 6,"['Weiss, Howard', 'Hertzberg, Vicki Stover', 'Dupont, Chris', 'Espinoza, Josh L.', 'Levy, Shawn', 'Nelson, Karen', 'Norris, Sharon', None]",Microb Ecol,,,True
ca8f30a35b564945dd2588c382a0e181a1e08662,PMC,Mental health workers perceptions of disaster response in China,http://dx.doi.org/10.1186/s12889-018-6313-9,PMC6318987,30606149,CC BY,"BACKGROUND: The post-disaster mental health crisis intervention (MHCI) system in China remains immature and unsystematic. We aim to report the perceptions of a large sample of MHCI workers and government administrators and provide recommendations for developing a national mental health disaster response management plan in China. METHODS: An in-depth qualitative study was conducted, collecting data from 20 focus-group discussions and 25 key stakeholder interviews. These recruited participants who had been involved in different types of disaster rescue across 7 provinces/cities where disasters have recently occurred. We used thematic analysis to analyze the data and relevant findings were extracted for policy recommendation. RESULTS: Mental health workers’ perspectives were examined in detailed according to four core themes: forms of organization, intervention pathway, intervention strategy and technique, and public health information. Post-disaster MHCI should be approached in teams that are integrated with emergency medicine systems, and be led by unified command management. All levels of local health and family planning commission should prepare post-disaster MHCI work plans and build response teams/emergency centres. Future training for MHCI workers should focus on: building a sense of trust within the team; clarifying each member’s role; strengthening the screening, assessment and referrals training for psychological professionals; and providing psychological intervention training for Chinese psychiatrists. It is necessary to set up guiding principles for disaster research ethics, mental health rehabilitation and media interaction. CONCLUSIONS: Through exploring and analyzing the perceptions of current disaster response mental health workers and government administrators, our findings provide essential recommendations for developing a national to county level post-disaster MHCI emergency management plan and can guide the formulation of relevant laws and regulation in China. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-018-6313-9) contains supplementary material, which is available to authorized users.",2019 Jan 3,"['Xi, Yingjun', 'Chen, Runsen', 'Gillespie, Amy L.', 'He, Yuyang', 'Jia, Chihua', 'Shi, Kuo', 'Yao, Yiming', 'Ma, Xin', 'Liu, Wei', 'Chan, Emily Ying Yang']",BMC Public Health,,,True
84785c6c2c5a963376b6314c430402e4fe3654e3,PMC,Drug Repurposing for Japanese Encephalitis Virus Infection by Systems Biology Methods,http://dx.doi.org/10.3390/molecules23123346,PMC6320907,30567313,CC BY,"Japanese encephalitis is a zoonotic disease caused by the Japanese encephalitis virus (JEV). It is mainly epidemic in Asia with an estimated 69,000 cases occurring per year. However, no approved agents are available for the treatment of JEV infection, and existing vaccines cannot control various types of JEV strains. Drug repurposing is a new concept for finding new indication of existing drugs, and, recently, the concept has been used to discover new antiviral agents. Identifying host proteins involved in the progress of JEV infection and using these proteins as targets are the center of drug repurposing for JEV infection. In this study, based on the gene expression data of JEV infection and the phenome-wide association study (PheWAS) data, we identified 286 genes that participate in the progress of JEV infection using systems biology methods. The enrichment analysis of these genes suggested that the genes identified by our methods were predominantly related to viral infection pathways and immune response-related pathways. We found that bortezomib, which can target these genes, may have an effect on the treatment of JEV infection. Subsequently, we evaluated the antiviral activity of bortezomib using a JEV-infected mouse model. The results showed that bortezomib can lower JEV-induced lethality in mice, alleviate suffering in JEV-infected mice and reduce the damage in brains caused by JEV infection. This work provides an agent with new indication to treat JEV infection.",2018 Dec 18,"['Lv, Bo-Min', 'Tong, Xin-Yu', 'Quan, Yuan', 'Liu, Meng-Yuan', 'Zhang, Qing-Ye', 'Song, Yun-Feng', 'Zhang, Hong-Yu']",Molecules,,,True
3899c4aad46100ad273f70ecf65f5454806d5117,PMC,Improving Encapsulation of Hydrophilic Chloroquine Diphosphate into Biodegradable Nanoparticles: A Promising Approach against Herpes Virus Simplex-1 Infection,http://dx.doi.org/10.3390/pharmaceutics10040255,PMC6320969,30513856,CC BY,"Chloroquine diphosphate (CQ) is a hydrophilic drug with low entrapment efficiency in hydrophobic nanoparticles (NP). Herpes simplex virus type 1 (HSV-1) is an enveloped double-stranded DNA virus worldwide known as a common human pathogen. This study aims to develop chloroquine-loaded poly(lactic acid) (PLA) nanoparticles (CQ-NP) to improve the chloroquine anti- HSV-1 efficacy. CQ-NP were successfully prepared using a modified emulsification-solvent evaporation method. Physicochemical properties of the NP were monitored using dynamic light scattering, atomic force microscopy, drug loading efficiency, and drug release studies. Spherical nanoparticles were produced with modal diameter of <300 nm, zeta potential of −20 mv and encapsulation efficiency of 64.1%. In vitro assays of CQ-NP performed in Vero E6 cells, using the MTT-assay, revealed different cytotoxicity levels. Blank nanoparticles (B-NP) were biocompatible. Finally, the antiviral activity tested by the plaque reduction assay revealed greater efficacy for CQ-NP compared to CQ at concentrations equal to or lower than 20 µg mL(−1) (p < 0.001). On the other hand, the B-NP had no antiviral activity. The CQ-NP has shown feasible properties and great potential to improve the antiviral activity of drugs.",2018 Dec 3,"['Lima, Tábata Loíse Cunha', 'Feitosa, Renata de Carvalho', 'dos Santos-Silva, Emanuell', 'dos Santos-Silva, Alaine Maria', 'Siqueira, Emerson Michell da Silva', 'Machado, Paula Renata Lima', 'Cornélio, Alianda Maira', 'do Egito, Eryvaldo Sócrates Tabosa', 'Fernandes-Pedrosa, Matheus de Freitas', 'Farias, Kleber Juvenal Silva', 'da Silva-Júnior, Arnóbio Antônio']",Pharmaceutics,,,True
8d7027f9c0c85c6aad1c9459d1c16f2b3b918280,PMC,The Multifaceted Roles of Autophagy in Flavivirus-Host Interactions,http://dx.doi.org/10.3390/ijms19123940,PMC6321027,30544615,CC BY,"Autophagy is an evolutionarily conserved cellular process in which intracellular components are eliminated via lysosomal degradation to supply nutrients for organelle biogenesis and metabolic homeostasis. Flavivirus infections underlie multiple human diseases and thus exert an immense burden on public health worldwide. Mounting evidence indicates that host autophagy is subverted to modulate the life cycles of flaviviruses, such as hepatitis C virus, dengue virus, Japanese encephalitis virus, West Nile virus and Zika virus. The diverse interplay between autophagy and flavivirus infection not only regulates viral growth in host cells but also counteracts host stress responses induced by viral infection. In this review, we summarize the current knowledge on the role of autophagy in the flavivirus life cycle. We also discuss the impacts of virus-induced autophagy on the pathogeneses of flavivirus-associated diseases and the potential use of autophagy as a therapeutic target for curing flavivirus infections and related human diseases.",2018 Dec 7,"Ke, Po-Yuan",Int J Mol Sci,,,True
7c852fa9a4b769ebffabda42452bac3fcb8af799,PMC,Self-Replicating RNA Viruses for RNA Therapeutics,http://dx.doi.org/10.3390/molecules23123310,PMC6321401,30551668,CC BY,"Self-replicating single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses, and rhabdoviruses provide efficient delivery and high-level expression of therapeutic genes due to their high capacity of RNA replication. This has contributed to novel approaches for therapeutic applications including vaccine development and gene therapy-based immunotherapy. Numerous studies in animal tumor models have demonstrated that self-replicating RNA viral vectors can generate antibody responses against infectious agents and tumor cells. Moreover, protection against challenges with pathogenic Ebola virus was obtained in primates immunized with alphaviruses and flaviviruses. Similarly, vaccinated animals have been demonstrated to withstand challenges with lethal doses of tumor cells. Furthermore, clinical trials have been conducted for several indications with self-amplifying RNA viruses. In this context, alphaviruses have been subjected to phase I clinical trials for a cytomegalovirus vaccine generating neutralizing antibodies in healthy volunteers, and for antigen delivery to dendritic cells providing clinically relevant antibody responses in cancer patients, respectively. Likewise, rhabdovirus particles have been subjected to phase I/II clinical trials showing good safety and immunogenicity against Ebola virus. Rhabdoviruses have generated promising results in phase III trials against Ebola virus. The purpose of this review is to summarize the achievements of using self-replicating RNA viruses for RNA therapy based on preclinical animal studies and clinical trials in humans.",2018 Dec 13,"Lundstrom, Kenneth",Molecules,,,True
59cee2c2d1c8e2b5c732523f10682153c278395c,PMC,mRNA-Mediated Duplexes Play Dual Roles in the Regulation of Bidirectional Ribosomal Frameshifting,http://dx.doi.org/10.3390/ijms19123867,PMC6321510,30518074,CC BY,"In contrast to −1 programmed ribosomal frameshifting (PRF) stimulation by an RNA pseudoknot downstream of frameshifting sites, a refolding upstream RNA hairpin juxtaposing the frameshifting sites attenuates −1 PRF in human cells and stimulates +1 frameshifting in yeast. This eukaryotic functional mimicry of the internal Shine-Dalgarno (SD) sequence-mediated duplex was confirmed directly in the 70S translation system, indicating that both frameshifting regulation activities of upstream hairpin are conserved between 70S and 80S ribosomes. Unexpectedly, a downstream pseudoknot also possessed two opposing hungry codon-mediated frameshifting regulation activities: attenuation of +1 frameshifting and stimulation of a non-canonical −1 frameshifting within the +1 frameshift-prone CUUUGA frameshifting site in the absence of release factor 2 (RF2) in vitro. However, the −1 frameshifting activity of the downstream pseudoknot is not coupled with its +1 frameshifting attenuation ability. Similarly, the +1 frameshifting activity of the upstream hairpin is not required for its −1 frameshifting attenuation function Thus, each of the mRNA duplexes flanking the two ends of a ribosomal mRNA-binding channel possesses two functions in bi-directional ribosomal frameshifting regulation: frameshifting stimulation and counteracting the frameshifting activity of each other.",2018 Dec 4,"['Huang, Wan-Ping', 'Cho, Che-Pei', 'Chang, Kung-Yao']",Int J Mol Sci,,,True
cc39f8acc7505bbd8dda460fd2aa481452e6dbbd,PMC,mRNA-Mediated Duplexes Play Dual Roles in the Regulation of Bidirectional Ribosomal Frameshifting,http://dx.doi.org/10.3390/ijms19123867,PMC6321510,30518074,CC BY,"In contrast to −1 programmed ribosomal frameshifting (PRF) stimulation by an RNA pseudoknot downstream of frameshifting sites, a refolding upstream RNA hairpin juxtaposing the frameshifting sites attenuates −1 PRF in human cells and stimulates +1 frameshifting in yeast. This eukaryotic functional mimicry of the internal Shine-Dalgarno (SD) sequence-mediated duplex was confirmed directly in the 70S translation system, indicating that both frameshifting regulation activities of upstream hairpin are conserved between 70S and 80S ribosomes. Unexpectedly, a downstream pseudoknot also possessed two opposing hungry codon-mediated frameshifting regulation activities: attenuation of +1 frameshifting and stimulation of a non-canonical −1 frameshifting within the +1 frameshift-prone CUUUGA frameshifting site in the absence of release factor 2 (RF2) in vitro. However, the −1 frameshifting activity of the downstream pseudoknot is not coupled with its +1 frameshifting attenuation ability. Similarly, the +1 frameshifting activity of the upstream hairpin is not required for its −1 frameshifting attenuation function Thus, each of the mRNA duplexes flanking the two ends of a ribosomal mRNA-binding channel possesses two functions in bi-directional ribosomal frameshifting regulation: frameshifting stimulation and counteracting the frameshifting activity of each other.",2018 Dec 4,"['Huang, Wan-Ping', 'Cho, Che-Pei', 'Chang, Kung-Yao']",Int J Mol Sci,,,False
386d7389837dbaa87d3b0119af4d965b197651f6,PMC,Simultaneous and systematic analysis of cellular and viral gene expression during Enterovirus 71-induced host shutoff,http://dx.doi.org/10.1007/s13238-018-0535-6,PMC6321815,29696588,CC BY,,2019 Jan 25,"['Lin, Yongquan', 'Wang, Yan', 'Li, Hui', 'Chen, Yuhang', 'Qiao, Wentao', 'Xie, Zhi', 'Tan, Juan', 'Yang, Zhilong']",Protein Cell,,,True
e8913cb59861302b5e0abb9eb28b1fdcdc2b71b7,PMC,Simultaneous and systematic analysis of cellular and viral gene expression during Enterovirus 71-induced host shutoff,http://dx.doi.org/10.1007/s13238-018-0535-6,PMC6321815,29696588,CC BY,,2019 Jan 25,"['Lin, Yongquan', 'Wang, Yan', 'Li, Hui', 'Chen, Yuhang', 'Qiao, Wentao', 'Xie, Zhi', 'Tan, Juan', 'Yang, Zhilong']",Protein Cell,,,True
0f880cb0b394ac20be2a2868fecaefd4d8f341b3,PMC,Dynamics of Virus-Specific Memory B Cells and Plasmablasts following Viral Infection of the Central Nervous System,http://dx.doi.org/10.1128/JVI.00875-18,PMC6321933,30333176,CC BY,"Humoral responses within the central nervous system (CNS) are common to many neurotropic viral infections, with antibody (Ab)-secreting cells (ASC) contributing to local protection. However, a role for virus-specific memory B cells (Bmem) within the CNS is poorly explored due to lack of robust phenotypic or functional identification in mice. This study takes advantage of the progeny of mice expressing tamoxifen-inducible Cre recombinase (Cre-ERT2) under the Aicda promoter crossed with Rosa26-loxP-tdTomato reporter mice (AID(Cre)-Rosa26(tdTomato)) to monitor B cells having undergone activation-induced cytidine deaminase (AID)-mediated somatic hypermutation (SHM) following neurotropic coronavirus infection. AID detection via tdTomato expression allowed tracking of virus-specific ASC and Bmem in priming and effector sites throughout infection. In draining lymph nodes, tdTomato-positive (tdTomato(+)) ASC were most prevalent prior to germinal center (GC) formation, but total tdTomato(+) B cells only peaked with robust GC formation at day 14 p.i. Moreover, their proportion of Bmem dominated over the proportion of ASC throughout infection. In the CNS, tdTomato(+) cells started emerging at day 14 p.i. While they initially comprised mainly Bmem, the proportions of ASC and Bmem became similar as tdTomato(+) B cells increased throughout viral persistence. Delayed tamoxifen treatment demonstrated ongoing CNS recruitment of tdTomato(+) B cells, mainly ASC, primed late during GC reactions. Overall, the data support the idea that virus-induced B cells exhibiting SHM require peripheral GC formation to emerge in the CNS. Ongoing GC reactions and regional signals further regulate dynamics within the CNS, with preferential maintenance of tdTomato(+) B cells in spinal cords relative to that in brains during viral persistence. IMPORTANCE The prevalence and role of antigen-specific Bmem in the CNS during viral encephalomyelitis is largely undefined. A lack of reliable markers identifying murine Bmem has made it difficult to assess their contribution to local antiviral protection via antigen presentation or conversion to ASC. Using reporter mice infected with neurotropic coronavirus to track virus-specific Bmem and ASC, this report demonstrates that both subsets only emerge in the CNS following peripheral GC formation and subsequently prevail. While early GC reactions supported preferential Bmem accumulation in the CNS, late GC reactions favored ASC accumulation, although Bmem outnumbered ASC in draining lymph nodes throughout infection. Importantly, virus-specific B cells undergoing sustained GC selection were continually recruited to the persistently infected CNS. Elucidating the factors governing temporal events within GCs, as well as regional CNS cues during viral persistence, will aid intervention to modulate CNS humoral responses in the context of infection and associated autoimmune pathologies.",2019 Jan 4,"['Atkinson, Jeffrey R.', 'Hwang, Mihyun', 'Reyes-Rodriguez, Angel', 'Bergmann, Cornelia C.']",J Virol,,,True
0edc8eae4da299b0d013f38e62efdca8cfb78c85,PMC,Oral faecal microbiota transplantation for the treatment of Clostridium difficile-associated diarrhoea in a dog: a case report,http://dx.doi.org/10.1186/s12917-018-1754-z,PMC6322325,30616615,CC BY,"BACKGROUND: Successful clinical outcomes of faecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection have been reported in humans and a marmoset. However, it has been unclear whether oral FMT was effective for the treatment of C. difficile-associated diarrhoea in dogs. CASE PRESENTATION: An 8-month-old, intact male French bulldog was presented with a 4-month history of intermittent large bowel diarrhoea. Physical and clinical examinations did not identify any specific causes for diarrhoea. Real-time PCR analysis and immunochromatography detected C. difficile antigen and toxin A&B genes and proteins in a faecal sample. Based on these findings, diarrhoea in the dog was considered to be induced by C. difficile-associated colitis. The dog was treated with oral FMT, in which a faecal solution obtained from a healthy beagle was orally administered to the subject. Stool consistency and frequency and faecal blood and mucus became normal 2–3 days after oral FMT, and real-time PCR analysis and immunochromatography was negative for C. difficile antigen and toxin A&B genes and proteins. No adverse events were observed. CONCLUSION: The present case report demonstrated that oral FMT was an effective treatment for C. difficile-associated diarrhoea in a dog. The findings in this report provide a rationale to evaluate clinical efficacy of oral FMT for other gastrointestinal diseases in dogs.",2019 Jan 7,"['Sugita, Koji', 'Yanuma, Nanako', 'Ohno, Hikaru', 'Takahashi, Kaho', 'Kawano, Koji', 'Morita, Hidetoshi', 'Ohmori, Keitaro']",BMC Vet Res,,,True
da9c2a65da6499124bab5ad5754dddf47fe0baaf,PMC,IMG/VR v.2.0: an integrated data management and analysis system for cultivated and environmental viral genomes,http://dx.doi.org/10.1093/nar/gky1127,PMC6323928,30407573,CC BY,"The Integrated Microbial Genome/Virus (IMG/VR) system v.2.0 (https://img.jgi.doe.gov/vr/) is the largest publicly available data management and analysis platform dedicated to viral genomics. Since the last report published in the 2016, NAR Database Issue, the data has tripled in size and currently contains genomes of 8389 cultivated reference viruses, 12 498 previously published curated prophages derived from cultivated microbial isolates, and 735 112 viral genomic fragments computationally predicted from assembled shotgun metagenomes. Nearly 60% of the viral genomes and genome fragments are clustered into 110 384 viral Operational Taxonomic Units (vOTUs) with two or more members. To improve data quality and predictions of host specificity, IMG/VR v.2.0 now separates prokaryotic and eukaryotic viruses, utilizes known prophage sequences to improve taxonomic assignments, and provides viral genome quality scores based on the estimated genome completeness. New features also include enhanced BLAST search capabilities for external queries. Finally, geographic map visualization to locate user-selected viral genomes or genome fragments has been implemented and download options have been extended. All of these features make IMG/VR v.2.0 a key resource for the study of viruses.",2019 Jan 8,"['Paez-Espino, David', 'Roux, Simon', 'Chen, I-Min\xa0A', 'Palaniappan, Krishna', 'Ratner, Anna', 'Chu, Ken', 'Huntemann, Marcel', 'Reddy, T\xa0B\xa0K', 'Pons, Joan\xa0Carles', 'Llabrés, Mercè', 'Eloe-Fadrosh, Emiley\xa0A', 'Ivanova, Natalia\xa0N', 'Kyrpides, Nikos\xa0C']",Nucleic Acids Res,,,True
44f03c77fc5f868225ece79cd3c3a3bc0e44f235,PMC,IMG/VR v.2.0: an integrated data management and analysis system for cultivated and environmental viral genomes,http://dx.doi.org/10.1093/nar/gky1127,PMC6323928,30407573,CC BY,"The Integrated Microbial Genome/Virus (IMG/VR) system v.2.0 (https://img.jgi.doe.gov/vr/) is the largest publicly available data management and analysis platform dedicated to viral genomics. Since the last report published in the 2016, NAR Database Issue, the data has tripled in size and currently contains genomes of 8389 cultivated reference viruses, 12 498 previously published curated prophages derived from cultivated microbial isolates, and 735 112 viral genomic fragments computationally predicted from assembled shotgun metagenomes. Nearly 60% of the viral genomes and genome fragments are clustered into 110 384 viral Operational Taxonomic Units (vOTUs) with two or more members. To improve data quality and predictions of host specificity, IMG/VR v.2.0 now separates prokaryotic and eukaryotic viruses, utilizes known prophage sequences to improve taxonomic assignments, and provides viral genome quality scores based on the estimated genome completeness. New features also include enhanced BLAST search capabilities for external queries. Finally, geographic map visualization to locate user-selected viral genomes or genome fragments has been implemented and download options have been extended. All of these features make IMG/VR v.2.0 a key resource for the study of viruses.",2019 Jan 8,"['Paez-Espino, David', 'Roux, Simon', 'Chen, I-Min\xa0A', 'Palaniappan, Krishna', 'Ratner, Anna', 'Chu, Ken', 'Huntemann, Marcel', 'Reddy, T\xa0B\xa0K', 'Pons, Joan\xa0Carles', 'Llabrés, Mercè', 'Eloe-Fadrosh, Emiley\xa0A', 'Ivanova, Natalia\xa0N', 'Kyrpides, Nikos\xa0C']",Nucleic Acids Res,,,False
2b4696bf4bc923a139e8508086f854ca52b690d0,PMC,UniProt: a worldwide hub of protein knowledge,http://dx.doi.org/10.1093/nar/gky1049,PMC6323992,30395287,CC BY,"The UniProt Knowledgebase is a collection of sequences and annotations for over 120 million proteins across all branches of life. Detailed annotations extracted from the literature by expert curators have been collected for over half a million of these proteins. These annotations are supplemented by annotations provided by rule based automated systems, and those imported from other resources. In this article we describe significant updates that we have made over the last 2 years to the resource. We have greatly expanded the number of Reference Proteomes that we provide and in particular we have focussed on improving the number of viral Reference Proteomes. The UniProt website has been augmented with new data visualizations for the subcellular localization of proteins as well as their structure and interactions. UniProt resources are available under a CC-BY (4.0) license via the web at https://www.uniprot.org/.",2019 Jan 8,,Nucleic Acids Res,,,True
1a7751b196054ed357f5a0f16eeac17ad2def269,PMC,Depletion of RIPK1 in hepatocytes exacerbates liver damage in fulminant viral hepatitis,http://dx.doi.org/10.1038/s41419-018-1277-3,PMC6325114,30622241,CC BY,"The protein kinase RIPK1 plays a crucial role at the crossroad of stress-induced signaling pathways that affects cell’s decision to live or die. The present study aimed to define the role of RIPK1 in hepatocytes during fulminant viral hepatitis, a worldwide syndrome mainly observed in hepatitis B virus (HBV) infected patients. Mice deficient for RIPK1, specifically in liver parenchymal cells (Ripk1(LPC-KO)) and their wild-type littermates (Ripk1(fl/fl)), were challenged by either the murine hepatitis virus type 3 (MHV3) or poly I:C, a synthetic analog of double-stranded RNA mimicking viral pathogen-associated molecular pattern. Ripk1(LPC-KO) mice developed more severe symptoms at early stage of the MHV3-induced fulminant hepatitis. Similarly, administration of poly I:C only triggered increase of systemic transaminases in Ripk1(LPC-KO) mice, reflecting liver damage through induced apoptosis as illustrated by cleaved-caspase 3 labeling of liver tissue sections. Neutralization of TNF-α or prior depletion of macrophages were able to prevent the appearance of apoptosis of hepatocytes in poly I:C-challenged Ripk1(LPC-KO) mice. Moreover, poly I:C never induced direct hepatocyte death in primary culture whatever the murine genotype, while it always stimulated an anti-viral response. Our investigations demonstrated that RIPK1 protects hepatocytes from TNF-α secreted from macrophages during viral induced fulminant hepatitis. These data emphasize the potential worsening risks of an HBV infection in people with polymorphism or homozygous amorphic mutations already described for the RIPK1 gene.",2019 Jan 8,"['Farooq, Muhammad', 'Filliol, Aveline', 'Simoes Eugénio, Mélanie', 'Piquet-Pellorce, Claire', 'Dion, Sarah', 'Raguenes-Nicol, Céline', 'Jan, Aurélien', 'Dimanche-Boitrel, Marie-Thérèse', 'Le Seyec, Jacques', 'Samson, Michel']",Cell Death Dis,,,True
7cccfb42207af2158ed271db543d30e82f801170,PMC,Clinical characteristics and viral etiologies of outpatients with acute respiratory infections in Huzhou of China: a retrospective study,http://dx.doi.org/10.1186/s12879-018-3668-6,PMC6325799,30621623,CC BY,"BACKGROUND: Viruses are commonly found in patients with acute respiratory infections (ARIs). However, the viral etiologies and clinical characteristics of outpatients with ARIs are poorly understood in China. Here, we identified the viral etiologies in outpatients with ARIs in Huzhou, China. RESULTS: Our results indicated that of 426 outpatients, 246 were positive for viruses. Of them, 221 were positive for a single virus, including influenza A, which comprised H3N2 (28.5%) and pandemic H1N1 (2009) (19.0%), enterovirus (10.4%), and influenza B (8.6%). Other single viruses were detected at less than 8.0%. Twenty-five patients were positively coinfected with two viruses. The prevalent viruses in coinfections were rhinovirus and H3N2 virus (28.0%). Viruses were major pathogens in young children (< 5 years) (75.0%). Coinfections were prevalent in older adults (11.9%) and young children (9.5%). Virus-positive outpatients presented higher temperatures and more sore throat, fatigue and shortness of breath than virus-negative outpatients. ARIs and most virus detections peaked during the winter, but enteroviruses emerged between April and September. CONCLUSION: Viruses are major agents of ARIs among outpatients in Huzhou, China. There was a variation in the distribution of viruses across different age groups and seasons. These findings are beneficial for planning prevention and treatment services for outpatients with ARIs.",2019 Jan 8,"['Wen, Xiaohong', 'Huang, Qiuling', 'Tao, Hong', 'Zou, Weihua', 'Gao, Min', 'Guo, Huihui', 'Yao, Xing', 'Cui, Dawei', 'Wang, Xiang']",BMC Infect Dis,,,True
451dd2d5f7ba1decdc08444bd05eb3d3ff6b09f8,PMC,Repositioning salicylanilide anthelmintic drugs to treat adenovirus infections,http://dx.doi.org/10.1038/s41598-018-37290-3,PMC6327057,30626902,CC BY,"The repositioning of drugs already approved by regulatory agencies for other indications is an emerging alternative for the development of new antimicrobial therapies. The repositioning process involves lower risks and costs than the de novo development of novel antimicrobial drugs. Currently, infections by adenovirus show a steady increment with a high clinical impact in immunosuppressed and immunocompetent patients. The lack of a safe and efficacious drug to treat these infections supports the search for new antiviral drugs. Here we evaluated the anti-adenovirus activity of niclosanide, oxyclozanide, and rafoxanide, three salicylanilide anthelmintic drugs. Also, we carried out the cytotoxicity evaluation and partial characterization of the mechanism of action of these drugs. The salicylanilide anthelmintic drugs showed significant anti-adenovirus activity at low micromolar concentrations with little cytotoxicity. Moreover, our mechanistic assays suggest differences in the way the drugs exert anti-adenovirus activity. Niclosamide and rafoxanide target transport of the HAdV particle from the endosome to the nuclear envelope, whilst oxyclozanide specifically targets adenovirus immediately early gene E1A transcription. Data suggests that the studied salicylanilide anthelmintic drugs could be suitable for further clinical evaluation for the development of new antiviral drugs to treat infections by adenovirus in immunosuppressed patients and in immunocompetent individuals with community-acquired pneumonia.",2019 Jan 9,"['Marrugal-Lorenzo, José A.', 'Serna-Gallego, Ana', 'Berastegui-Cabrera, Judith', 'Pachón, Jerónimo', 'Sánchez-Céspedes, Javier']",Sci Rep,,,False
51340894a896316b58653a60c48da9c16b3ad0e3,PMC,Repositioning salicylanilide anthelmintic drugs to treat adenovirus infections,http://dx.doi.org/10.1038/s41598-018-37290-3,PMC6327057,30626902,CC BY,"The repositioning of drugs already approved by regulatory agencies for other indications is an emerging alternative for the development of new antimicrobial therapies. The repositioning process involves lower risks and costs than the de novo development of novel antimicrobial drugs. Currently, infections by adenovirus show a steady increment with a high clinical impact in immunosuppressed and immunocompetent patients. The lack of a safe and efficacious drug to treat these infections supports the search for new antiviral drugs. Here we evaluated the anti-adenovirus activity of niclosanide, oxyclozanide, and rafoxanide, three salicylanilide anthelmintic drugs. Also, we carried out the cytotoxicity evaluation and partial characterization of the mechanism of action of these drugs. The salicylanilide anthelmintic drugs showed significant anti-adenovirus activity at low micromolar concentrations with little cytotoxicity. Moreover, our mechanistic assays suggest differences in the way the drugs exert anti-adenovirus activity. Niclosamide and rafoxanide target transport of the HAdV particle from the endosome to the nuclear envelope, whilst oxyclozanide specifically targets adenovirus immediately early gene E1A transcription. Data suggests that the studied salicylanilide anthelmintic drugs could be suitable for further clinical evaluation for the development of new antiviral drugs to treat infections by adenovirus in immunosuppressed patients and in immunocompetent individuals with community-acquired pneumonia.",2019 Jan 9,"['Marrugal-Lorenzo, José A.', 'Serna-Gallego, Ana', 'Berastegui-Cabrera, Judith', 'Pachón, Jerónimo', 'Sánchez-Céspedes, Javier']",Sci Rep,,,True
235fab2608254fb0e97f003cef3b4694bc003756,PMC,The C/EBP Homologous Protein (CHOP) Transcription Factor Functions in Endoplasmic Reticulum Stress-Induced Apoptosis and Microbial Infection,http://dx.doi.org/10.3389/fimmu.2018.03083,PMC6328441,30662442,CC BY,"Apoptosis is a form of cell death by which the body maintains the homeostasis of the internal environment. Apoptosis is an initiative cell death process that is controlled by genes and is mainly divided into endogenous pathways (mitochondrial pathway), exogenous pathways (death receptor pathway), and apoptotic pathways induced by endoplasmic reticulum (ER) stress. The homeostasis imbalance in ER results in ER stress. Under specific conditions, ER stress can be beneficial to the body; however, if ER protein homeostasis is not restored, the prolonged activation of the unfolded protein response may initiate apoptotic cell death via the up-regulation of the C/EBP homologous protein (CHOP). CHOP plays an important role in ER stress-induced apoptosis and this review focuses on its multifunctional roles in that process, as well as its role in apoptosis during microbial infection. We summarize the upstream and downstream pathways of CHOP in ER stress induced apoptosis. We also focus on the newest discoveries in the functions of CHOP-induced apoptosis during microbial infection, including DNA and RNA viruses and some species of bacteria. Understanding how CHOP functions during microbial infection will assist with the development of antimicrobial therapies.",2019 Jan 4,"['Hu, Hai', 'Tian, Mingxing', 'Ding, Chan', 'Yu, Shengqing']",Front Immunol,,,True
bb2ffc635f751dcffbca3bd712293321ca79bcd9,PMC,SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target,http://dx.doi.org/10.1038/s41467-018-08015-x,PMC6328544,30631056,CC BY,"Viruses are obligate intracellular microbes that exploit the host metabolic machineries to meet their biosynthetic demands, making these host pathways potential therapeutic targets. Here, by exploring a lipid library, we show that AM580, a retinoid derivative and RAR-α agonist, is highly potent in interrupting the life cycle of diverse viruses including Middle East respiratory syndrome coronavirus and influenza A virus. Using click chemistry, the overexpressed sterol regulatory element binding protein (SREBP) is shown to interact with AM580, which accounts for its broad-spectrum antiviral activity. Mechanistic studies pinpoint multiple SREBP proteolytic processes and SREBP-regulated lipid biosynthesis pathways, including the downstream viral protein palmitoylation and double-membrane vesicles formation, that are indispensable for virus replication. Collectively, our study identifies a basic lipogenic transactivation event with broad relevance to human viral infections and represents SREBP as a potential target for the development of broad-spectrum antiviral strategies.",2019 Jan 10,"['Yuan, Shuofeng', 'Chu, Hin', 'Chan, Jasper Fuk-Woo', 'Ye, Zi-Wei', 'Wen, Lei', 'Yan, Bingpeng', 'Lai, Pok-Man', 'Tee, Kah-Meng', 'Huang, Jingjing', 'Chen, Dongdong', 'Li, Cun', 'Zhao, Xiaoyu', 'Yang, Dong', 'Chiu, Man Chun', 'Yip, Cyril', 'Poon, Vincent Kwok-Man', 'Chan, Chris Chung-Sing', 'Sze, Kong-Hung', 'Zhou, Jie', 'Chan, Ivy Hau-Yee', 'Kok, Kin-Hang', 'To, Kelvin Kai-Wang', 'Kao, Richard Yi-Tsun', 'Lau, Johnson Yiu-Nam', 'Jin, Dong-Yan', 'Perlman, Stanley', 'Yuen, Kwok-Yung']",Nat Commun,,,False
99fbfb118e293a937583b9338256f9d216cf8c5e,PMC,SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target,http://dx.doi.org/10.1038/s41467-018-08015-x,PMC6328544,30631056,CC BY,"Viruses are obligate intracellular microbes that exploit the host metabolic machineries to meet their biosynthetic demands, making these host pathways potential therapeutic targets. Here, by exploring a lipid library, we show that AM580, a retinoid derivative and RAR-α agonist, is highly potent in interrupting the life cycle of diverse viruses including Middle East respiratory syndrome coronavirus and influenza A virus. Using click chemistry, the overexpressed sterol regulatory element binding protein (SREBP) is shown to interact with AM580, which accounts for its broad-spectrum antiviral activity. Mechanistic studies pinpoint multiple SREBP proteolytic processes and SREBP-regulated lipid biosynthesis pathways, including the downstream viral protein palmitoylation and double-membrane vesicles formation, that are indispensable for virus replication. Collectively, our study identifies a basic lipogenic transactivation event with broad relevance to human viral infections and represents SREBP as a potential target for the development of broad-spectrum antiviral strategies.",2019 Jan 10,"['Yuan, Shuofeng', 'Chu, Hin', 'Chan, Jasper Fuk-Woo', 'Ye, Zi-Wei', 'Wen, Lei', 'Yan, Bingpeng', 'Lai, Pok-Man', 'Tee, Kah-Meng', 'Huang, Jingjing', 'Chen, Dongdong', 'Li, Cun', 'Zhao, Xiaoyu', 'Yang, Dong', 'Chiu, Man Chun', 'Yip, Cyril', 'Poon, Vincent Kwok-Man', 'Chan, Chris Chung-Sing', 'Sze, Kong-Hung', 'Zhou, Jie', 'Chan, Ivy Hau-Yee', 'Kok, Kin-Hang', 'To, Kelvin Kai-Wang', 'Kao, Richard Yi-Tsun', 'Lau, Johnson Yiu-Nam', 'Jin, Dong-Yan', 'Perlman, Stanley', 'Yuen, Kwok-Yung']",Nat Commun,,,True
92ea97f34bacf1c103cc9418a7c18ff41ce59dbe,PMC,SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target,http://dx.doi.org/10.1038/s41467-018-08015-x,PMC6328544,30631056,CC BY,"Viruses are obligate intracellular microbes that exploit the host metabolic machineries to meet their biosynthetic demands, making these host pathways potential therapeutic targets. Here, by exploring a lipid library, we show that AM580, a retinoid derivative and RAR-α agonist, is highly potent in interrupting the life cycle of diverse viruses including Middle East respiratory syndrome coronavirus and influenza A virus. Using click chemistry, the overexpressed sterol regulatory element binding protein (SREBP) is shown to interact with AM580, which accounts for its broad-spectrum antiviral activity. Mechanistic studies pinpoint multiple SREBP proteolytic processes and SREBP-regulated lipid biosynthesis pathways, including the downstream viral protein palmitoylation and double-membrane vesicles formation, that are indispensable for virus replication. Collectively, our study identifies a basic lipogenic transactivation event with broad relevance to human viral infections and represents SREBP as a potential target for the development of broad-spectrum antiviral strategies.",2019 Jan 10,"['Yuan, Shuofeng', 'Chu, Hin', 'Chan, Jasper Fuk-Woo', 'Ye, Zi-Wei', 'Wen, Lei', 'Yan, Bingpeng', 'Lai, Pok-Man', 'Tee, Kah-Meng', 'Huang, Jingjing', 'Chen, Dongdong', 'Li, Cun', 'Zhao, Xiaoyu', 'Yang, Dong', 'Chiu, Man Chun', 'Yip, Cyril', 'Poon, Vincent Kwok-Man', 'Chan, Chris Chung-Sing', 'Sze, Kong-Hung', 'Zhou, Jie', 'Chan, Ivy Hau-Yee', 'Kok, Kin-Hang', 'To, Kelvin Kai-Wang', 'Kao, Richard Yi-Tsun', 'Lau, Johnson Yiu-Nam', 'Jin, Dong-Yan', 'Perlman, Stanley', 'Yuen, Kwok-Yung']",Nat Commun,,,False
7be137cf73f58b2ffb648b1a964116f5eba57c84,PMC,SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target,http://dx.doi.org/10.1038/s41467-018-08015-x,PMC6328544,30631056,CC BY,"Viruses are obligate intracellular microbes that exploit the host metabolic machineries to meet their biosynthetic demands, making these host pathways potential therapeutic targets. Here, by exploring a lipid library, we show that AM580, a retinoid derivative and RAR-α agonist, is highly potent in interrupting the life cycle of diverse viruses including Middle East respiratory syndrome coronavirus and influenza A virus. Using click chemistry, the overexpressed sterol regulatory element binding protein (SREBP) is shown to interact with AM580, which accounts for its broad-spectrum antiviral activity. Mechanistic studies pinpoint multiple SREBP proteolytic processes and SREBP-regulated lipid biosynthesis pathways, including the downstream viral protein palmitoylation and double-membrane vesicles formation, that are indispensable for virus replication. Collectively, our study identifies a basic lipogenic transactivation event with broad relevance to human viral infections and represents SREBP as a potential target for the development of broad-spectrum antiviral strategies.",2019 Jan 10,"['Yuan, Shuofeng', 'Chu, Hin', 'Chan, Jasper Fuk-Woo', 'Ye, Zi-Wei', 'Wen, Lei', 'Yan, Bingpeng', 'Lai, Pok-Man', 'Tee, Kah-Meng', 'Huang, Jingjing', 'Chen, Dongdong', 'Li, Cun', 'Zhao, Xiaoyu', 'Yang, Dong', 'Chiu, Man Chun', 'Yip, Cyril', 'Poon, Vincent Kwok-Man', 'Chan, Chris Chung-Sing', 'Sze, Kong-Hung', 'Zhou, Jie', 'Chan, Ivy Hau-Yee', 'Kok, Kin-Hang', 'To, Kelvin Kai-Wang', 'Kao, Richard Yi-Tsun', 'Lau, Johnson Yiu-Nam', 'Jin, Dong-Yan', 'Perlman, Stanley', 'Yuen, Kwok-Yung']",Nat Commun,,,False
0ce5bbc5edc608a6561d64e63edaad4a2bcad084,PMC,SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target,http://dx.doi.org/10.1038/s41467-018-08015-x,PMC6328544,30631056,CC BY,"Viruses are obligate intracellular microbes that exploit the host metabolic machineries to meet their biosynthetic demands, making these host pathways potential therapeutic targets. Here, by exploring a lipid library, we show that AM580, a retinoid derivative and RAR-α agonist, is highly potent in interrupting the life cycle of diverse viruses including Middle East respiratory syndrome coronavirus and influenza A virus. Using click chemistry, the overexpressed sterol regulatory element binding protein (SREBP) is shown to interact with AM580, which accounts for its broad-spectrum antiviral activity. Mechanistic studies pinpoint multiple SREBP proteolytic processes and SREBP-regulated lipid biosynthesis pathways, including the downstream viral protein palmitoylation and double-membrane vesicles formation, that are indispensable for virus replication. Collectively, our study identifies a basic lipogenic transactivation event with broad relevance to human viral infections and represents SREBP as a potential target for the development of broad-spectrum antiviral strategies.",2019 Jan 10,"['Yuan, Shuofeng', 'Chu, Hin', 'Chan, Jasper Fuk-Woo', 'Ye, Zi-Wei', 'Wen, Lei', 'Yan, Bingpeng', 'Lai, Pok-Man', 'Tee, Kah-Meng', 'Huang, Jingjing', 'Chen, Dongdong', 'Li, Cun', 'Zhao, Xiaoyu', 'Yang, Dong', 'Chiu, Man Chun', 'Yip, Cyril', 'Poon, Vincent Kwok-Man', 'Chan, Chris Chung-Sing', 'Sze, Kong-Hung', 'Zhou, Jie', 'Chan, Ivy Hau-Yee', 'Kok, Kin-Hang', 'To, Kelvin Kai-Wang', 'Kao, Richard Yi-Tsun', 'Lau, Johnson Yiu-Nam', 'Jin, Dong-Yan', 'Perlman, Stanley', 'Yuen, Kwok-Yung']",Nat Commun,,,True
8357e742ce4e988fbae529ff603c81ac5b974b27,PMC,Identification and characterization of GLDC as host susceptibility gene to severe influenza,http://dx.doi.org/10.15252/emmm.201809528,PMC6328914,30498026,CC BY,"Glycine decarboxylase (GLDC) was prioritized as a candidate susceptibility gene to severe influenza in humans. The higher expression of GLDC derived from genetic variations may confer a higher risk to H7N9 and severe H1N1 infection. We sought to characterize GLDC as functional susceptibility gene that GLDC may intrinsically regulate antiviral response, thereby impacting viral replication and disease outcome. We demonstrated that GLDC inhibitor AOAA and siRNA depletion boosted IFNβ‐ and IFN‐stimulated genes (ISGs) in combination with PolyI:C stimulation. GLDC inhibition and depletion significantly amplified antiviral response of type I IFNs and ISGs upon viral infection and suppressed the replication of H1N1 and H7N9 viruses. Consistently, GLDC overexpression significantly promoted viral replication due to the attenuated antiviral responses. Moreover, GLDC inhibition in H1N1‐infected BALB/c mice recapitulated the amplified antiviral response and suppressed viral growth. AOAA provided potent protection to the infected mice from lethal infection, comparable to a standard antiviral against influenza viruses. Collectively, GLDC regulates cellular antiviral response and orchestrates viral growth. GLDC is a functional susceptibility gene to severe influenza in humans.",2019 Jan 28,"['Zhou, Jie', 'Wang, Dong', 'Wong, Bosco Ho‐Yin', 'Li, Cun', 'Poon, Vincent Kwok‐Man', 'Wen, Lei', 'Zhao, Xiaoyu', 'Chiu, Man Chun', 'Liu, Xiaojuan', 'Ye, Ziwei', 'Yuan, Shuofeng', 'Sze, Kong‐Hung', 'Chan, Jasper Fuk‐Woo', 'Chu, Hin', 'To, Kelvin Kai‐Wang', 'Yuen, Kwok Yung']",EMBO Mol Med,,,True
2ec6a171036b53b0c21a39abdfd12756fd02ace6,PMC,Identification and characterization of GLDC as host susceptibility gene to severe influenza,http://dx.doi.org/10.15252/emmm.201809528,PMC6328914,30498026,CC BY,"Glycine decarboxylase (GLDC) was prioritized as a candidate susceptibility gene to severe influenza in humans. The higher expression of GLDC derived from genetic variations may confer a higher risk to H7N9 and severe H1N1 infection. We sought to characterize GLDC as functional susceptibility gene that GLDC may intrinsically regulate antiviral response, thereby impacting viral replication and disease outcome. We demonstrated that GLDC inhibitor AOAA and siRNA depletion boosted IFNβ‐ and IFN‐stimulated genes (ISGs) in combination with PolyI:C stimulation. GLDC inhibition and depletion significantly amplified antiviral response of type I IFNs and ISGs upon viral infection and suppressed the replication of H1N1 and H7N9 viruses. Consistently, GLDC overexpression significantly promoted viral replication due to the attenuated antiviral responses. Moreover, GLDC inhibition in H1N1‐infected BALB/c mice recapitulated the amplified antiviral response and suppressed viral growth. AOAA provided potent protection to the infected mice from lethal infection, comparable to a standard antiviral against influenza viruses. Collectively, GLDC regulates cellular antiviral response and orchestrates viral growth. GLDC is a functional susceptibility gene to severe influenza in humans.",2019 Jan 28,"['Zhou, Jie', 'Wang, Dong', 'Wong, Bosco Ho‐Yin', 'Li, Cun', 'Poon, Vincent Kwok‐Man', 'Wen, Lei', 'Zhao, Xiaoyu', 'Chiu, Man Chun', 'Liu, Xiaojuan', 'Ye, Ziwei', 'Yuan, Shuofeng', 'Sze, Kong‐Hung', 'Chan, Jasper Fuk‐Woo', 'Chu, Hin', 'To, Kelvin Kai‐Wang', 'Yuen, Kwok Yung']",EMBO Mol Med,,,True
fdf34a84076c5fb91cbea284f72ffd3bf33c1b10,PMC,Identification and characterization of GLDC as host susceptibility gene to severe influenza,http://dx.doi.org/10.15252/emmm.201809528,PMC6328914,30498026,CC BY,"Glycine decarboxylase (GLDC) was prioritized as a candidate susceptibility gene to severe influenza in humans. The higher expression of GLDC derived from genetic variations may confer a higher risk to H7N9 and severe H1N1 infection. We sought to characterize GLDC as functional susceptibility gene that GLDC may intrinsically regulate antiviral response, thereby impacting viral replication and disease outcome. We demonstrated that GLDC inhibitor AOAA and siRNA depletion boosted IFNβ‐ and IFN‐stimulated genes (ISGs) in combination with PolyI:C stimulation. GLDC inhibition and depletion significantly amplified antiviral response of type I IFNs and ISGs upon viral infection and suppressed the replication of H1N1 and H7N9 viruses. Consistently, GLDC overexpression significantly promoted viral replication due to the attenuated antiviral responses. Moreover, GLDC inhibition in H1N1‐infected BALB/c mice recapitulated the amplified antiviral response and suppressed viral growth. AOAA provided potent protection to the infected mice from lethal infection, comparable to a standard antiviral against influenza viruses. Collectively, GLDC regulates cellular antiviral response and orchestrates viral growth. GLDC is a functional susceptibility gene to severe influenza in humans.",2019 Jan 28,"['Zhou, Jie', 'Wang, Dong', 'Wong, Bosco Ho‐Yin', 'Li, Cun', 'Poon, Vincent Kwok‐Man', 'Wen, Lei', 'Zhao, Xiaoyu', 'Chiu, Man Chun', 'Liu, Xiaojuan', 'Ye, Ziwei', 'Yuan, Shuofeng', 'Sze, Kong‐Hung', 'Chan, Jasper Fuk‐Woo', 'Chu, Hin', 'To, Kelvin Kai‐Wang', 'Yuen, Kwok Yung']",EMBO Mol Med,,,False
1cf05c949d31e988d09d26620290ff924a86d678,PMC,Identification and characterization of GLDC as host susceptibility gene to severe influenza,http://dx.doi.org/10.15252/emmm.201809528,PMC6328914,30498026,CC BY,"Glycine decarboxylase (GLDC) was prioritized as a candidate susceptibility gene to severe influenza in humans. The higher expression of GLDC derived from genetic variations may confer a higher risk to H7N9 and severe H1N1 infection. We sought to characterize GLDC as functional susceptibility gene that GLDC may intrinsically regulate antiviral response, thereby impacting viral replication and disease outcome. We demonstrated that GLDC inhibitor AOAA and siRNA depletion boosted IFNβ‐ and IFN‐stimulated genes (ISGs) in combination with PolyI:C stimulation. GLDC inhibition and depletion significantly amplified antiviral response of type I IFNs and ISGs upon viral infection and suppressed the replication of H1N1 and H7N9 viruses. Consistently, GLDC overexpression significantly promoted viral replication due to the attenuated antiviral responses. Moreover, GLDC inhibition in H1N1‐infected BALB/c mice recapitulated the amplified antiviral response and suppressed viral growth. AOAA provided potent protection to the infected mice from lethal infection, comparable to a standard antiviral against influenza viruses. Collectively, GLDC regulates cellular antiviral response and orchestrates viral growth. GLDC is a functional susceptibility gene to severe influenza in humans.",2019 Jan 28,"['Zhou, Jie', 'Wang, Dong', 'Wong, Bosco Ho‐Yin', 'Li, Cun', 'Poon, Vincent Kwok‐Man', 'Wen, Lei', 'Zhao, Xiaoyu', 'Chiu, Man Chun', 'Liu, Xiaojuan', 'Ye, Ziwei', 'Yuan, Shuofeng', 'Sze, Kong‐Hung', 'Chan, Jasper Fuk‐Woo', 'Chu, Hin', 'To, Kelvin Kai‐Wang', 'Yuen, Kwok Yung']",EMBO Mol Med,,,False
80a278b4912f11c65a1e2ecc75897b6609f6820e,PMC,Identification and characterization of GLDC as host susceptibility gene to severe influenza,http://dx.doi.org/10.15252/emmm.201809528,PMC6328914,30498026,CC BY,"Glycine decarboxylase (GLDC) was prioritized as a candidate susceptibility gene to severe influenza in humans. The higher expression of GLDC derived from genetic variations may confer a higher risk to H7N9 and severe H1N1 infection. We sought to characterize GLDC as functional susceptibility gene that GLDC may intrinsically regulate antiviral response, thereby impacting viral replication and disease outcome. We demonstrated that GLDC inhibitor AOAA and siRNA depletion boosted IFNβ‐ and IFN‐stimulated genes (ISGs) in combination with PolyI:C stimulation. GLDC inhibition and depletion significantly amplified antiviral response of type I IFNs and ISGs upon viral infection and suppressed the replication of H1N1 and H7N9 viruses. Consistently, GLDC overexpression significantly promoted viral replication due to the attenuated antiviral responses. Moreover, GLDC inhibition in H1N1‐infected BALB/c mice recapitulated the amplified antiviral response and suppressed viral growth. AOAA provided potent protection to the infected mice from lethal infection, comparable to a standard antiviral against influenza viruses. Collectively, GLDC regulates cellular antiviral response and orchestrates viral growth. GLDC is a functional susceptibility gene to severe influenza in humans.",2019 Jan 28,"['Zhou, Jie', 'Wang, Dong', 'Wong, Bosco Ho‐Yin', 'Li, Cun', 'Poon, Vincent Kwok‐Man', 'Wen, Lei', 'Zhao, Xiaoyu', 'Chiu, Man Chun', 'Liu, Xiaojuan', 'Ye, Ziwei', 'Yuan, Shuofeng', 'Sze, Kong‐Hung', 'Chan, Jasper Fuk‐Woo', 'Chu, Hin', 'To, Kelvin Kai‐Wang', 'Yuen, Kwok Yung']",EMBO Mol Med,,,True
8cef766849d0d8ad7a5ff33d7f66299de03cf583,PMC,Pathogenicity and immunogenicity of attenuated porcine epidemic diarrhea virus PC22A strain in conventional weaned pigs,http://dx.doi.org/10.1186/s12917-018-1756-x,PMC6329175,30634958,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV) causes diarrhea in all ages of pigs with 50–100% mortality rates in neonatal piglets. In the United States, inactivated and subunit PEDV vaccines for pregnant sows are available, but fail to induce sufficient protection in neonatal piglets farrowed from PEDV naïve sows. A safe and efficacious live attenuated vaccine that can prime mucosal immune responses is urgently needed. In this study, we evaluated the safety and efficacy of two attenuated PEDV vaccine candidates, the emerging non-S INDEL PEDV strain PC22A at the 100th cell culture passage level - Clone no. 4 (P100C4) and at the 120th passage level (P120), in weaned pigs. RESULTS: Four groups of 40-day-old weaned pigs were inoculated orally with PEDV PC22A-P3 (virulent), -P100C4, -P120, and mock, respectively, and challenged with the P3 virus at 24 days post-inoculation (dpi). After inoculation, P3 caused diarrhea in all pigs with a high level of fecal viral RNA shedding. P100C4 and P120 did not cause diarrhea in pigs, although viral RNA was detected in feces of all pigs, except for one P100C4-inoculated pig. Compared with the P120 group, P3- and P100C4-inoculated pigs had higher serum PEDV-specific IgG and viral neutralizing (VN) antibody (Ab) titers at 14 dpi. After the challenge, no pigs in the P3 group but all pigs in the P100C4, P120, and mock groups had diarrhea. Compared with the P120 group, pigs in the P100C4 group had a more rapid decline in fecal PEDV RNA shedding titers, higher titers of serum PEDV-specific IgG, IgA, and VN Abs, and higher numbers of intestinal IgA Ab-secreting cells. CONCLUSIONS: PEDV PC22A P100C4 and P120 were fully attenuated in weaned pigs but failed to elicit protection against virulent P3 challenge. P100C4 induced higher PEDV-specific antibody responses than P120 post inoculation resulting in a greater anamnestic response post challenge. Therefore, P100C4 potentially could be tested as a priming vaccine or be further modified using reverse genetics. It also can be administered in multiple doses or be combined with inactivated or subunit vaccines and adjuvants as a PEDV vaccination regimen, whose efficacy can be tested in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1756-x) contains supplementary material, which is available to authorized users.",2019 Jan 11,"['Lin, Chun-Ming', 'Ghimire, Shristi', 'Hou, Yixuan', 'Boley, Patricia', 'Langel, Stephanie N.', 'Vlasova, Anastasia N.', 'Saif, Linda J.', 'Wang, Qiuhong']",BMC Vet Res,,,True
9f9f2fd83cf45c04586def3818497de7391bbbee,PMC,Infectious disease and economics: The case for considering multi-sectoral impacts,http://dx.doi.org/10.1016/j.onehlt.2018.100080,PMC6330263,30671528,CC BY,"Beyond the public health impacts of regional or global emerging and endemic infectious disease events lay wider socioeconomic consequences that are often not considered in risk or impact assessments. With rapid and extensive international travel and trade, such events can elicit economic shock waves far beyond the realm of traditional health sectors and original geographical range of a pathogen. While private sector organizations are impacted indirectly by these disease events, they are under-recognized yet effective stakeholders that can provide critical information, resources, and key partnerships to public and private health systems in response to and in preparation for potential infectious disease events and their socioeconomic consequences.",2019 Jan 9,"['Smith, Kristine M.', 'Machalaba, Catherine C.', 'Seifman, Richard', 'Feferholtz, Yasha', 'Karesh, William B.']",One Health,,,False
5e00a4c6f4faed178e0f2c24b7c2678c9404f84c,PMC,"Genetic diversity of the Yokose virus, XYBX1332, isolated from bats (Myotis daubentonii) in China",http://dx.doi.org/10.1186/s12985-018-1107-3,PMC6330390,30634973,CC BY,"BACKGROUND: Yokose virus was first isolated from bats (Miniopterus fuliginosus) collected in Yokosuka, Japan, in 1971, and is a new member of the family Flaviviridae, genus Flavivirus. In this study, we isolated a Yokose virus from a serum sample of Myotis daubentonii (order Chiroptera, family Vespertilionidae) collected in Yunnan province, China in 2013. METHODS: The serum specimens of bat were used to inoculate in BHK-21 and Vero E6 cells for virus isolation. Then the viral complete genome sequence was obtained and was used for phylogenetic analysis performed by BEAST software package. RESULTS: The virus was shown to have cytopathic effects in mammalian cells (BHK-21 and Vero E6). Genome sequencing indicated that it has a single open reading frame (ORF), with a genome of 10,785 nucleotides in total. Phylogenetic analysis of the viral genome suggests that XYBX1332 is a Yokose virus (YOKV) of the genus Flavivirus. Nucleotide and amino acid homology levels of the ORF of XYBX1332 and Oita-36, the original strain of YOKV, were 72 and 82%, respectively. The ORFs of XYBX1332 and Oita-36 encode 3422 and 3425 amino acids, respectively. In addition, the non-coding regions (5′- and 3′-untranslated regions [UTRs]) of these two strains differ in length and the homology of the 5′- and 3′-UTRs was 81.5 and 78.3%, respectively. CONCLUSION: The isolation of YOKV (XYBX1332) from inland China thousands of kilometers from Yokosuka, Japan, suggests that the geographical distribution of YOKV is not limited to the islands of Japan and that it can also exist in the inland areas of Asia. However, there are large differences between the Chinese and Japanese YOKV strains in viral genome.",2019 Jan 11,"['Feng, Yun', 'Ren, Xiaojie', 'Xu, Ziqian', 'Fu, Shihong', 'Li, Xiaolong', 'Zhang, Hailin', 'Yang, Weihong', 'Zhang, Yuzhen', 'Liang, Guodong']",Virol J,,,True
1d2c4cd6798ba4eb5e8e062248a7853df4bc74ca,PMC,Metagenomic analysis of viruses in toilet waste from long distance flights—A new procedure for global infectious disease surveillance,http://dx.doi.org/10.1371/journal.pone.0210368,PMC6331095,30640944,CC BY,"Human viral pathogens are a major public health threat. Reliable information that accurately describes and characterizes the global occurrence and transmission of human viruses is essential to support national and global priority setting, public health actions, and treatment decisions. However, large areas of the globe are currently without surveillance due to limited health care infrastructure and lack of international cooperation. We propose a novel surveillance strategy, using metagenomic analysis of toilet material from international air flights as a method for worldwide viral disease surveillance. The aim of this study was to design, implement, and evaluate a method for viral analysis of airplane toilet waste enabling simultaneous detection and quantification of a wide range of human viral pathogens. Toilet waste from 19 international airplanes was analyzed for viral content, using viral capture probes followed by high-throughput sequencing. Numerous human pathogens were detected including enteric and respiratory viruses. Several geographic trends were observed with samples originating from South Asia having significantly higher viral species richness as well as higher abundances of salivirus A, aichivirus A and enterovirus B, compared to samples originating from North Asia and North America. In addition, certain city specific trends were observed, including high numbers of rotaviruses in airplanes departing from Islamabad. Based on this study we believe that central sampling and analysis at international airports could be a useful supplement for global viral surveillance, valuable for outbreak detection and for guiding public health resources.",2019 Jan 14,"['Hjelmsø, Mathis Hjort', 'Mollerup, Sarah', 'Jensen, Randi Holm', 'Pietroni, Carlotta', 'Lukjancenko, Oksana', 'Schultz, Anna Charlotte', 'Aarestrup, Frank M.', 'Hansen, Anders Johannes']",PLoS One,,,True
f3bb9ce9274648a4dcbcb460a61f40ba063b3804,PMC,Metagenomic analysis of viruses in toilet waste from long distance flights—A new procedure for global infectious disease surveillance,http://dx.doi.org/10.1371/journal.pone.0210368,PMC6331095,30640944,CC BY,"Human viral pathogens are a major public health threat. Reliable information that accurately describes and characterizes the global occurrence and transmission of human viruses is essential to support national and global priority setting, public health actions, and treatment decisions. However, large areas of the globe are currently without surveillance due to limited health care infrastructure and lack of international cooperation. We propose a novel surveillance strategy, using metagenomic analysis of toilet material from international air flights as a method for worldwide viral disease surveillance. The aim of this study was to design, implement, and evaluate a method for viral analysis of airplane toilet waste enabling simultaneous detection and quantification of a wide range of human viral pathogens. Toilet waste from 19 international airplanes was analyzed for viral content, using viral capture probes followed by high-throughput sequencing. Numerous human pathogens were detected including enteric and respiratory viruses. Several geographic trends were observed with samples originating from South Asia having significantly higher viral species richness as well as higher abundances of salivirus A, aichivirus A and enterovirus B, compared to samples originating from North Asia and North America. In addition, certain city specific trends were observed, including high numbers of rotaviruses in airplanes departing from Islamabad. Based on this study we believe that central sampling and analysis at international airports could be a useful supplement for global viral surveillance, valuable for outbreak detection and for guiding public health resources.",2019 Jan 14,"['Hjelmsø, Mathis Hjort', 'Mollerup, Sarah', 'Jensen, Randi Holm', 'Pietroni, Carlotta', 'Lukjancenko, Oksana', 'Schultz, Anna Charlotte', 'Aarestrup, Frank M.', 'Hansen, Anders Johannes']",PLoS One,,,False
e06eef429570ccdd9375526eb297bef3e81438b8,PMC,Metagenomic analysis of viruses in toilet waste from long distance flights—A new procedure for global infectious disease surveillance,http://dx.doi.org/10.1371/journal.pone.0210368,PMC6331095,30640944,CC BY,"Human viral pathogens are a major public health threat. Reliable information that accurately describes and characterizes the global occurrence and transmission of human viruses is essential to support national and global priority setting, public health actions, and treatment decisions. However, large areas of the globe are currently without surveillance due to limited health care infrastructure and lack of international cooperation. We propose a novel surveillance strategy, using metagenomic analysis of toilet material from international air flights as a method for worldwide viral disease surveillance. The aim of this study was to design, implement, and evaluate a method for viral analysis of airplane toilet waste enabling simultaneous detection and quantification of a wide range of human viral pathogens. Toilet waste from 19 international airplanes was analyzed for viral content, using viral capture probes followed by high-throughput sequencing. Numerous human pathogens were detected including enteric and respiratory viruses. Several geographic trends were observed with samples originating from South Asia having significantly higher viral species richness as well as higher abundances of salivirus A, aichivirus A and enterovirus B, compared to samples originating from North Asia and North America. In addition, certain city specific trends were observed, including high numbers of rotaviruses in airplanes departing from Islamabad. Based on this study we believe that central sampling and analysis at international airports could be a useful supplement for global viral surveillance, valuable for outbreak detection and for guiding public health resources.",2019 Jan 14,"['Hjelmsø, Mathis Hjort', 'Mollerup, Sarah', 'Jensen, Randi Holm', 'Pietroni, Carlotta', 'Lukjancenko, Oksana', 'Schultz, Anna Charlotte', 'Aarestrup, Frank M.', 'Hansen, Anders Johannes']",PLoS One,,,False
21aad6e5451a91d00f32f5837c640f407328c686,PMC,Metagenomic analysis of viruses in toilet waste from long distance flights—A new procedure for global infectious disease surveillance,http://dx.doi.org/10.1371/journal.pone.0210368,PMC6331095,30640944,CC BY,"Human viral pathogens are a major public health threat. Reliable information that accurately describes and characterizes the global occurrence and transmission of human viruses is essential to support national and global priority setting, public health actions, and treatment decisions. However, large areas of the globe are currently without surveillance due to limited health care infrastructure and lack of international cooperation. We propose a novel surveillance strategy, using metagenomic analysis of toilet material from international air flights as a method for worldwide viral disease surveillance. The aim of this study was to design, implement, and evaluate a method for viral analysis of airplane toilet waste enabling simultaneous detection and quantification of a wide range of human viral pathogens. Toilet waste from 19 international airplanes was analyzed for viral content, using viral capture probes followed by high-throughput sequencing. Numerous human pathogens were detected including enteric and respiratory viruses. Several geographic trends were observed with samples originating from South Asia having significantly higher viral species richness as well as higher abundances of salivirus A, aichivirus A and enterovirus B, compared to samples originating from North Asia and North America. In addition, certain city specific trends were observed, including high numbers of rotaviruses in airplanes departing from Islamabad. Based on this study we believe that central sampling and analysis at international airports could be a useful supplement for global viral surveillance, valuable for outbreak detection and for guiding public health resources.",2019 Jan 14,"['Hjelmsø, Mathis Hjort', 'Mollerup, Sarah', 'Jensen, Randi Holm', 'Pietroni, Carlotta', 'Lukjancenko, Oksana', 'Schultz, Anna Charlotte', 'Aarestrup, Frank M.', 'Hansen, Anders Johannes']",PLoS One,,,False
736aca806c50c6673209bf8bd84a192a6a8e87de,PMC,Metagenomic analysis of viruses in toilet waste from long distance flights—A new procedure for global infectious disease surveillance,http://dx.doi.org/10.1371/journal.pone.0210368,PMC6331095,30640944,CC BY,"Human viral pathogens are a major public health threat. Reliable information that accurately describes and characterizes the global occurrence and transmission of human viruses is essential to support national and global priority setting, public health actions, and treatment decisions. However, large areas of the globe are currently without surveillance due to limited health care infrastructure and lack of international cooperation. We propose a novel surveillance strategy, using metagenomic analysis of toilet material from international air flights as a method for worldwide viral disease surveillance. The aim of this study was to design, implement, and evaluate a method for viral analysis of airplane toilet waste enabling simultaneous detection and quantification of a wide range of human viral pathogens. Toilet waste from 19 international airplanes was analyzed for viral content, using viral capture probes followed by high-throughput sequencing. Numerous human pathogens were detected including enteric and respiratory viruses. Several geographic trends were observed with samples originating from South Asia having significantly higher viral species richness as well as higher abundances of salivirus A, aichivirus A and enterovirus B, compared to samples originating from North Asia and North America. In addition, certain city specific trends were observed, including high numbers of rotaviruses in airplanes departing from Islamabad. Based on this study we believe that central sampling and analysis at international airports could be a useful supplement for global viral surveillance, valuable for outbreak detection and for guiding public health resources.",2019 Jan 14,"['Hjelmsø, Mathis Hjort', 'Mollerup, Sarah', 'Jensen, Randi Holm', 'Pietroni, Carlotta', 'Lukjancenko, Oksana', 'Schultz, Anna Charlotte', 'Aarestrup, Frank M.', 'Hansen, Anders Johannes']",PLoS One,,,False
0c3365dc054fac2cadd624dffcba5910be0eceba,PMC,A Host Factor GPNMB Restricts Porcine Circovirus Type 2 (PCV2) Replication and Interacts With PCV2 ORF5 Protein,http://dx.doi.org/10.3389/fmicb.2018.03295,PMC6331448,30671053,CC BY,"Porcine circovirus type 2 (PCV2) is the infectious agent of postweaning multisystemic wasting syndrome (PMWS). The recently discovered open reading frame 5 (ORF5) in PCV2 genome encodes a non-structural protein. Previous study revealed that ORF5 protein inhibits cell proliferation and may interact with host transmembrane glycoprotein NMB (GPNMB). However, whether the GPNMB affects PCV2 replication and the underlying molecular mechanisms are still unknown. In this study, the transcriptome maps of PCV2-infected and ORF5-transfected porcine alveolar macrophages 3D4/2 (PAM) cells were profiled. The GPNMB gene was down-regulated in PCV2-infected and ORF5-transfected PAMs. By using glutathione S-transferase (GST) pull-down, co-immunoprecipitation (co-IP) and confocal microscopy approaches, we convincingly showed that PCV2 ORF5 protein interacts with GPNMB. Furthermore, by utilizing lentivirus mediated overexpression or knockdown approach, we showed that the cellular GPNMB significantly inhibits PCV2 replication and ORF5 expression. Moreover, GPNMB overexpressing leads to an increased Cyclin A expression and a reduced S phase, whereas GPNMB knockdown causes a decreased Cyclin A expression and a prolonged S phase. In conclusion, we identified a novel host factor GPNMB that interacts with PCV2 ORF5 protein and restricts PCV2 replication.",2019 Jan 8,"['Guo, Kangkang', 'Xu, Lei', 'Wu, Mengmeng', 'Hou, Yufeng', 'Jiang, Yanfen', 'Lv, Jiangman', 'Xu, Panpan', 'Fan, Zhixin', 'Zhang, Ruiqi', 'Xing, Fushan', 'Zhang, Yanming']",Front Microbiol,,,False
ae0700fe06361c6d9e2286332ba467940ec9f89e,PMC,A Host Factor GPNMB Restricts Porcine Circovirus Type 2 (PCV2) Replication and Interacts With PCV2 ORF5 Protein,http://dx.doi.org/10.3389/fmicb.2018.03295,PMC6331448,30671053,CC BY,"Porcine circovirus type 2 (PCV2) is the infectious agent of postweaning multisystemic wasting syndrome (PMWS). The recently discovered open reading frame 5 (ORF5) in PCV2 genome encodes a non-structural protein. Previous study revealed that ORF5 protein inhibits cell proliferation and may interact with host transmembrane glycoprotein NMB (GPNMB). However, whether the GPNMB affects PCV2 replication and the underlying molecular mechanisms are still unknown. In this study, the transcriptome maps of PCV2-infected and ORF5-transfected porcine alveolar macrophages 3D4/2 (PAM) cells were profiled. The GPNMB gene was down-regulated in PCV2-infected and ORF5-transfected PAMs. By using glutathione S-transferase (GST) pull-down, co-immunoprecipitation (co-IP) and confocal microscopy approaches, we convincingly showed that PCV2 ORF5 protein interacts with GPNMB. Furthermore, by utilizing lentivirus mediated overexpression or knockdown approach, we showed that the cellular GPNMB significantly inhibits PCV2 replication and ORF5 expression. Moreover, GPNMB overexpressing leads to an increased Cyclin A expression and a reduced S phase, whereas GPNMB knockdown causes a decreased Cyclin A expression and a prolonged S phase. In conclusion, we identified a novel host factor GPNMB that interacts with PCV2 ORF5 protein and restricts PCV2 replication.",2019 Jan 8,"['Guo, Kangkang', 'Xu, Lei', 'Wu, Mengmeng', 'Hou, Yufeng', 'Jiang, Yanfen', 'Lv, Jiangman', 'Xu, Panpan', 'Fan, Zhixin', 'Zhang, Ruiqi', 'Xing, Fushan', 'Zhang, Yanming']",Front Microbiol,,,True
8d0dc902f68228a84345abe956a41bb58ea01ef3,PMC,DNA Aptamers in the Diagnosis and Treatment of Human Diseases,http://dx.doi.org/10.3390/molecules201219739,PMC6332121,26610462,CC BY,"Aptamers have a promising role in the field of life science and have been extensively researched for application as analytical tools, therapeutic agents and as vehicles for targeted drug delivery. Compared with RNA aptamers, DNA aptamers have inherent advantages in stability and facility of generation and synthesis. To better understand the specific potential of DNA aptamers, an overview of the progress in the generation and application of DNA aptamers in human disease diagnosis and therapy are presented in this review. Special attention is given to researches that are relatively close to practical application. DNA aptamers are expected to have great potential in the diagnosis and treatment of human diseases.",2015 Nov 25,"['Zhu, Qinchang', 'Liu, Ge', 'Kai, Masaaki']",Molecules,,,True
d107ccddb5e20fc5a311869da6760711f2f1f8e1,PMC,"Phosphonylated Acyclic Guanosine Analogues with the 1,2,3-Triazole Linker",http://dx.doi.org/10.3390/molecules201018789,PMC6332235,26501246,CC BY,"A novel series of {4-[(2-amino-6-chloro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates and {4-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates as acyclic analogues of guanosine were synthesized and assessed for antiviral activity against a broad range of DNA and RNA viruses and for their cytostatic activity toward three cancerous cell lines (HeLa, L1210 and CEM). They were devoid of antiviral activity; however, several phosphonates were found slightly cytostatic against HeLa cells at an IC(50) in the 80–210 µM range. Compounds (1R,2S)-17k and (1S,2S)-17k showed the highest inhibitory effects (IC(50) = 15–30 µM) against the proliferation of murine leukemia (L1210) and human T-lymphocyte (CEM) cell lines.",2015 Oct 16,"['Głowacka, Iwona E.', 'Andrei, Graciela', 'Schols, Dominique', 'Snoeck, Robert', 'Piotrowska, Dorota G.']",Molecules,,,True
ef4bd0f82e4290dd3d826add75846fee85ff1181,PMC,"Synthesis, Characterization, and Anti-Cancer Activity of Some New N′-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives",http://dx.doi.org/10.3390/molecules200814638,PMC6332339,26287132,CC BY,"Eight novel N′-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4a–h were synthesized and fully characterized by IR, NMR ((1)H-NMR and (13)C-NMR), elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC(50) values between 3 and 7 μM) as compared to the known anti-cancer drug 5-Fluorouracil (IC(50) 32–50 μM). Among the tested compounds, 4a showed specificity against leukaemia (Jurkat) cells, with an IC(50) value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines.",2015 Aug 13,"['El-Faham, Ayman', 'Farooq, Muhammad', 'Khattab, Sherine N.', 'Abutaha, Nael', 'Wadaan, Mohammad A.', 'Ghabbour, Hazem A.', 'Fun, Hoong-Kun']",Molecules,,,True
3e0d6011d8e23ccd51b0c3ee0382b78b9e65ebfd,PMC,"Synthesis, Characterization, and Anti-Cancer Activity of Some New N′-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives",http://dx.doi.org/10.3390/molecules200814638,PMC6332339,26287132,CC BY,"Eight novel N′-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4a–h were synthesized and fully characterized by IR, NMR ((1)H-NMR and (13)C-NMR), elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC(50) values between 3 and 7 μM) as compared to the known anti-cancer drug 5-Fluorouracil (IC(50) 32–50 μM). Among the tested compounds, 4a showed specificity against leukaemia (Jurkat) cells, with an IC(50) value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines.",2015 Aug 13,"['El-Faham, Ayman', 'Farooq, Muhammad', 'Khattab, Sherine N.', 'Abutaha, Nael', 'Wadaan, Mohammad A.', 'Ghabbour, Hazem A.', 'Fun, Hoong-Kun']",Molecules,,,False
1c7230a768a9650c409a13c25b42dcf5f7f3392c,PMC,Oligonucleotide Functionalised Microbeads: Indispensable Tools for High-Throughput Aptamer Selection,http://dx.doi.org/10.3390/molecules201219766,PMC6332362,26633328,CC BY,"The functionalisation of microbeads with oligonucleotides has become an indispensable technique for high-throughput aptamer selection in SELEX protocols. In addition to simplifying the separation of binding and non-binding aptamer candidates, microbeads have facilitated the integration of other technologies such as emulsion PCR (ePCR) and Fluorescence Activated Cell Sorting (FACS) to high-throughput selection techniques. Within these systems, monoclonal aptamer microbeads can be individually generated and assayed to assess aptamer candidate fitness thereby helping eliminate stochastic effects which are common to classical SELEX techniques. Such techniques have given rise to aptamers with 1000 times greater binding affinities when compared to traditional SELEX. Another emerging technique is Fluorescence Activated Droplet Sorting (FADS) whereby selection does not rely on binding capture allowing evolution of a greater diversity of aptamer properties such as fluorescence or enzymatic activity. Within this review we explore examples and applications of oligonucleotide functionalised microbeads in aptamer selection and reflect upon new opportunities arising for aptamer science.",2015 Dec 1,"['Fraser, Lewis A.', 'Kinghorn, Andrew B.', 'Tang, Marco S. L.', 'Cheung, Yee-Wai', 'Lim, Bryce', 'Liang, Shaolin', 'Dirkzwager, Roderick M.', 'Tanner, Julian A.']",Molecules,,,True
bd907eded401f2594ef37b2f448ebf71046bd1dc,PMC,Anorectal Cancer with Bone Marrow and Leptomeningeal Metastases,http://dx.doi.org/10.1155/2018/9246139,PMC6332972,30693122,CC BY,"This is an interesting case of anorectal signet ring carcinoma with first presentation of an early stage disease, showing the aggressive disease and the undetectable behavior of this type of histology which can mislead diagnosis. Brain/CNS metastasis from colorectal cancer (CRC) is rare occurring in 3% of cases, and leptomeningeal carcinomatosis (LMC) is extremely rare in CRC (<0.02%). Symptoms and signs of LMC are pleomorphic and may be localized to three compartments: cerebral hemispheres, cranial nerves, and spinal cords and roots. Treatment of metastatic rectal cancer has been improving over the last few years with a lot of changes toward longer survival and improvement in quality of life and to change the disease into a chronic condition. However, in our case, the overall survival from the onset of LMC was 3 weeks only. Revising the evidence in the treatment of signet ring histology of rectal cancer, there is no specific treatment recommendation that is for this histology and for such very aggressive behavior which could be considered as a separate entity to the classic adenocarcinoma histology.",2018 Dec 30,"['Zeeneldin, Ahmed', 'Al-Dhaibani, Nasser', 'Saleh, Yasser M.', 'Ismail, Amal Mostafa', 'Alzibair, Zuhair', 'Moona, Mohamed Shafi', 'Mohamed, Wael']",Case Rep Oncol Med,,,True
c8e11bd3e14d4e681675fd8063c2896692d9e674,PMC,Respiratory Virus Infections in Hematopoietic Cell Transplant Recipients,http://dx.doi.org/10.3389/fmicb.2018.03294,PMC6333648,30687278,CC BY,"Highly immunocompromised pediatric and adult hematopoietic cell transplant (HCT) recipients frequently experience respiratory infections caused by viruses that are less virulent in immunocompetent individuals. Most of these infections, with the exception of rhinovirus as well as adenovirus and parainfluenza virus in tropical areas, are seasonal variable and occur before and after HCT. Infectious disease management includes sampling of respiratory specimens from nasopharyngeal washes or swabs as well as sputum and tracheal or tracheobronchial lavages. These are subjected to improved diagnostic tools including multiplex PCR assays that are routinely used allowing for expedient detection of all respiratory viruses. Disease progression along with high mortality is frequently associated with respiratory syncytial virus, parainfluenza virus, influenza virus, and metapneumovirus infections. In this review, we discuss clinical findings and the appropriate use of diagnostic measures. Additionally, we also discuss treatment options and suggest new drug formulations that might prove useful in treating respiratory viral infections. Finally, we shed light on the role of the state of immune reconstitution and on the use of immunosuppressive drugs on the outcome of infection.",2019 Jan 9,"['Pochon, Cécile', 'Voigt, Sebastian']",Front Microbiol,,,True
6b60cd0bf36070ca9ee5a9fa65ac9ddd3b61bcd4,PMC,Rabbit Hemorrhagic Disease Virus Non-structural Protein 6 Induces Apoptosis in Rabbit Kidney Cells,http://dx.doi.org/10.3389/fmicb.2018.03308,PMC6333657,30687286,CC BY,"Rabbit hemorrhagic disease (RHD) is a highly contagious disease caused by rabbit hemorrhagic disease virus (RHDV). Previous research has shown that RHDV induces apoptosis in numerous cell types, although the molecular mechanisms underlying the apoptosis induced by RHDV are not well understood. One possible factor is non-structural protein 6 (NSP6), a 3C-like protease that plays an important role in processing viral polyprotein precursors into mature non-structural proteins. To fully establish a role for NSP6, the present study examined the effects of ectopic expression of the protein in rabbit (RK13) and human (HeLa and HepG2) cells. We found that NSP6 suppressed cell viability and promoted apoptosis in all three cell types in a dose-dependent manner. We also identified increased caspase-3, -8, and -9 activities in RK13 cell, and an increased Bax to Bcl2 mRNA ratio. Mechanistically, the ability of NSP6 to induce apoptosis was impaired by mutation of the catalytic His27 residue. Our study has shown that RHDV NSP6 can induce apoptosis in host cells and is likely an important contributor to RHDV-induced apoptosis and pathogenesis.",2019 Jan 9,"['Chen, Mengmeng', 'Liu, Xing', 'Hu, Bo', 'Fan, Zhiyu', 'Song, Yanhua', 'Wei, Houjun', 'Qiu, Rulong', 'Xu, Weizhong', 'Zhu, Weifeng', 'Wang, Fang']",Front Microbiol,,,True
069d6ce905dc7992f5bc8692218ca3969ab3e227,PMC,Antiviral Protection by IFITM3 In Vivo,http://dx.doi.org/10.1007/s40588-018-0103-0,PMC6334760,30662816,CC BY,"PURPOSE OF REVIEW: Interferon-induced transmembrane protein 3 (IFITM3) is a cellular restriction factor that blocks fusion between virus and host membranes. Here, we provide an introduction to IFITM3 and the biochemical regulation underlying its antiviral activity. Further, we analyze and summarize the published literature examining phenotypes of IFITM3 knockout mice upon infections with viral pathogens and discuss the controversial association between single nucleotide polymorphisms (SNPs) in the human IFITM3 gene and severe virus infections. RECENT FINDINGS: Recent publications show that IFITM3 knockout mice experience more severe pathologies than wild-type mice in diverse virus infections, including infections with influenza A virus, West Nile virus, Chikungunya virus, Venezuelan equine encephalitis virus, respiratory syncytial virus, and cytomegalovirus. Likewise, numerous studies of humans of Chinese ancestry have associated the IFITM3 SNP rs12252-C with severe influenza virus infections, though examinations of other populations, such as Europeans, in which this SNP is rare, have largely failed to identify an association with severe infections. A second SNP, rs34481144-A, found in the human IFITM3 promoter has also recently been reported to be a risk allele for severe influenza virus infections. SUMMARY: There is significant evidence for a protective role of IFITM3 against virus infections in both mice and humans, though additional work is required to identify the range of pathogens restricted by IFITM3 and the mechanisms by which human SNPs affect IFITM3 levels or functionality.",2018 Dec 3,"['Zani, Ashley', 'Yount, Jacob S.']",Curr Clin Microbiol Rep,,,True
51d3450393a2a698cfe8ae3e94cb9d8f556e43ff,PMC,Rapid interferon independent expression of IFITM3 following T cell activation protects cells from influenza virus infection,http://dx.doi.org/10.1371/journal.pone.0210132,PMC6334895,30650117,CC BY,"Interferon-induced transmembrane protein 3 (IFITM3) is a potent antiviral protein that enhances cellular resistance to a variety of pathogens, including influenza virus. Classically defined as an interferon-stimulated gene, expression of IFITM3 on cells is rapidly up-regulated in response to type I and II interferon. Here we found that IFITM3 is rapidly up-regulated by T cells following their activation and this occurred independently of type I and II interferon and the interferon regulatory factors 3 and 7. Up-regulation of IFITM3 on effector T cells protected these cells from virus infection and imparted a survival advantage at sites of virus infection. Our results show that IFITM3 expression on effector T cells is crucial for these cells to mediate their effector function and highlights an interferon independent pathway for the induction of IFITM3 which, if targeted, could be an effective approach to harness the activity of IFITM3 for infection prevention.",2019 Jan 16,"['Bedford, James G.', 'O’Keeffe, Meredith', 'Reading, Patrick C.', 'Wakim, Linda M.']",PLoS One,,,True
f92ff61dd94295f7b403411bdd705daf757a7de4,PMC,Rapid interferon independent expression of IFITM3 following T cell activation protects cells from influenza virus infection,http://dx.doi.org/10.1371/journal.pone.0210132,PMC6334895,30650117,CC BY,"Interferon-induced transmembrane protein 3 (IFITM3) is a potent antiviral protein that enhances cellular resistance to a variety of pathogens, including influenza virus. Classically defined as an interferon-stimulated gene, expression of IFITM3 on cells is rapidly up-regulated in response to type I and II interferon. Here we found that IFITM3 is rapidly up-regulated by T cells following their activation and this occurred independently of type I and II interferon and the interferon regulatory factors 3 and 7. Up-regulation of IFITM3 on effector T cells protected these cells from virus infection and imparted a survival advantage at sites of virus infection. Our results show that IFITM3 expression on effector T cells is crucial for these cells to mediate their effector function and highlights an interferon independent pathway for the induction of IFITM3 which, if targeted, could be an effective approach to harness the activity of IFITM3 for infection prevention.",2019 Jan 16,"['Bedford, James G.', 'O’Keeffe, Meredith', 'Reading, Patrick C.', 'Wakim, Linda M.']",PLoS One,,,False
e15883476900762204d5680298c50153e9f3389f,PMC,Rapid interferon independent expression of IFITM3 following T cell activation protects cells from influenza virus infection,http://dx.doi.org/10.1371/journal.pone.0210132,PMC6334895,30650117,CC BY,"Interferon-induced transmembrane protein 3 (IFITM3) is a potent antiviral protein that enhances cellular resistance to a variety of pathogens, including influenza virus. Classically defined as an interferon-stimulated gene, expression of IFITM3 on cells is rapidly up-regulated in response to type I and II interferon. Here we found that IFITM3 is rapidly up-regulated by T cells following their activation and this occurred independently of type I and II interferon and the interferon regulatory factors 3 and 7. Up-regulation of IFITM3 on effector T cells protected these cells from virus infection and imparted a survival advantage at sites of virus infection. Our results show that IFITM3 expression on effector T cells is crucial for these cells to mediate their effector function and highlights an interferon independent pathway for the induction of IFITM3 which, if targeted, could be an effective approach to harness the activity of IFITM3 for infection prevention.",2019 Jan 16,"['Bedford, James G.', 'O’Keeffe, Meredith', 'Reading, Patrick C.', 'Wakim, Linda M.']",PLoS One,,,False
4b6aeec74cce9ad00d644273fb8bc959dc6a3770,PMC,Rapid interferon independent expression of IFITM3 following T cell activation protects cells from influenza virus infection,http://dx.doi.org/10.1371/journal.pone.0210132,PMC6334895,30650117,CC BY,"Interferon-induced transmembrane protein 3 (IFITM3) is a potent antiviral protein that enhances cellular resistance to a variety of pathogens, including influenza virus. Classically defined as an interferon-stimulated gene, expression of IFITM3 on cells is rapidly up-regulated in response to type I and II interferon. Here we found that IFITM3 is rapidly up-regulated by T cells following their activation and this occurred independently of type I and II interferon and the interferon regulatory factors 3 and 7. Up-regulation of IFITM3 on effector T cells protected these cells from virus infection and imparted a survival advantage at sites of virus infection. Our results show that IFITM3 expression on effector T cells is crucial for these cells to mediate their effector function and highlights an interferon independent pathway for the induction of IFITM3 which, if targeted, could be an effective approach to harness the activity of IFITM3 for infection prevention.",2019 Jan 16,"['Bedford, James G.', 'O’Keeffe, Meredith', 'Reading, Patrick C.', 'Wakim, Linda M.']",PLoS One,,,False
ea8720c191d3890314e8dbd7e9002794e4c30339,PMC,Rapid interferon independent expression of IFITM3 following T cell activation protects cells from influenza virus infection,http://dx.doi.org/10.1371/journal.pone.0210132,PMC6334895,30650117,CC BY,"Interferon-induced transmembrane protein 3 (IFITM3) is a potent antiviral protein that enhances cellular resistance to a variety of pathogens, including influenza virus. Classically defined as an interferon-stimulated gene, expression of IFITM3 on cells is rapidly up-regulated in response to type I and II interferon. Here we found that IFITM3 is rapidly up-regulated by T cells following their activation and this occurred independently of type I and II interferon and the interferon regulatory factors 3 and 7. Up-regulation of IFITM3 on effector T cells protected these cells from virus infection and imparted a survival advantage at sites of virus infection. Our results show that IFITM3 expression on effector T cells is crucial for these cells to mediate their effector function and highlights an interferon independent pathway for the induction of IFITM3 which, if targeted, could be an effective approach to harness the activity of IFITM3 for infection prevention.",2019 Jan 16,"['Bedford, James G.', 'O’Keeffe, Meredith', 'Reading, Patrick C.', 'Wakim, Linda M.']",PLoS One,,,False
b1dc12337fc29030e033e8feaf5cc107535d72d4,PMC,Genetic Evidence of Middle East Respiratory Syndrome Coronavirus (MERS-Cov) and Widespread Seroprevalence among Camels in Kenya,http://dx.doi.org/10.1007/s12250-018-0076-4,PMC6335226,30570714,CC BY,"We describe the first genome isolation of Middle East respiratory syndrome coronavirus (MERS-CoV) in Kenya. This fatal zoonotic pathogen was first described in the Kingdom of Saudi Arabia in 2012. Epidemiological and molecular evidence revealed zoonotic transmission from camels to humans and between humans. Currently, MERS-CoV is classified by the WHO as having high pandemic potential requiring greater surveillance. Previous studies of MERS-CoV in Kenya mainly focused on site-specific and archived camel and human serum samples for antibodies. We conducted active nationwide cross-sectional surveillance of camels and humans in Kenya, targeting both nasal swabs and plasma samples from 1,163 camels and 486 humans collected from January 2016 to June 2018. A total of 792 camel plasma samples were positive by ELISA. Seroprevalence increased with age, and the highest prevalence was observed in adult camels (82.37%, 95% confidence interval (CI) 79.50–84.91). More female camels were significantly seropositive (74.28%, 95% CI 71.14–77.19) than male camels (P < 0.001) (53.74%, 95% CI 48.48–58.90). Only 11 camel nasal swabs were positive for MERS-CoV by reverse transcription-quantitative PCR. Phylogenetic analysis of whole genome sequences showed that Kenyan MERS-CoV clustered within sub-clade C2, which is associated with the African clade, but did not contain signature deletions of orf4b in African viruses. None of the human plasma screened contained neutralizing antibodies against MERS-CoV. This study confirms the geographically widespread occurrence of MERS-CoV in Kenyan camels. Further one-health surveillance approaches in camels, wildlife, and human populations are needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-018-0076-4) contains supplementary material, which is available to authorized users.",2018 Dec 20,"['Ommeh, Sheila', 'Zhang, Wei', 'Zohaib, Ali', 'Chen, Jing', 'Zhang, Huajun', 'Hu, Ben', 'Ge, Xing-Yi', 'Yang, Xing-Lou', 'Masika, Moses', 'Obanda, Vincent', 'Luo, Yun', 'Li, Shan', 'Waruhiu, Cecilia', 'Li, Bei', 'Zhu, Yan', 'Ouma, Desterio', 'Odendo, Vincent', 'Wang, Lin-Fa', 'Anderson, Danielle E.', 'Lichoti, Jacqueline', 'Mungube, Erick', 'Gakuya, Francis', 'Zhou, Peng', 'Ngeiywa, Kisa-Juma', 'Yan, Bing', 'Agwanda, Bernard', 'Shi, Zheng-Li']",Virol Sin,,,False
d6750dff2734f993de45ffc3020428036b15ac21,PMC,Genetic Evidence of Middle East Respiratory Syndrome Coronavirus (MERS-Cov) and Widespread Seroprevalence among Camels in Kenya,http://dx.doi.org/10.1007/s12250-018-0076-4,PMC6335226,30570714,CC BY,"We describe the first genome isolation of Middle East respiratory syndrome coronavirus (MERS-CoV) in Kenya. This fatal zoonotic pathogen was first described in the Kingdom of Saudi Arabia in 2012. Epidemiological and molecular evidence revealed zoonotic transmission from camels to humans and between humans. Currently, MERS-CoV is classified by the WHO as having high pandemic potential requiring greater surveillance. Previous studies of MERS-CoV in Kenya mainly focused on site-specific and archived camel and human serum samples for antibodies. We conducted active nationwide cross-sectional surveillance of camels and humans in Kenya, targeting both nasal swabs and plasma samples from 1,163 camels and 486 humans collected from January 2016 to June 2018. A total of 792 camel plasma samples were positive by ELISA. Seroprevalence increased with age, and the highest prevalence was observed in adult camels (82.37%, 95% confidence interval (CI) 79.50–84.91). More female camels were significantly seropositive (74.28%, 95% CI 71.14–77.19) than male camels (P < 0.001) (53.74%, 95% CI 48.48–58.90). Only 11 camel nasal swabs were positive for MERS-CoV by reverse transcription-quantitative PCR. Phylogenetic analysis of whole genome sequences showed that Kenyan MERS-CoV clustered within sub-clade C2, which is associated with the African clade, but did not contain signature deletions of orf4b in African viruses. None of the human plasma screened contained neutralizing antibodies against MERS-CoV. This study confirms the geographically widespread occurrence of MERS-CoV in Kenyan camels. Further one-health surveillance approaches in camels, wildlife, and human populations are needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-018-0076-4) contains supplementary material, which is available to authorized users.",2018 Dec 20,"['Ommeh, Sheila', 'Zhang, Wei', 'Zohaib, Ali', 'Chen, Jing', 'Zhang, Huajun', 'Hu, Ben', 'Ge, Xing-Yi', 'Yang, Xing-Lou', 'Masika, Moses', 'Obanda, Vincent', 'Luo, Yun', 'Li, Shan', 'Waruhiu, Cecilia', 'Li, Bei', 'Zhu, Yan', 'Ouma, Desterio', 'Odendo, Vincent', 'Wang, Lin-Fa', 'Anderson, Danielle E.', 'Lichoti, Jacqueline', 'Mungube, Erick', 'Gakuya, Francis', 'Zhou, Peng', 'Ngeiywa, Kisa-Juma', 'Yan, Bing', 'Agwanda, Bernard', 'Shi, Zheng-Li']",Virol Sin,,,True
ab1216072d2b617ce819d2201747699262b5177d,PMC,Chikungunya as a paradigm for emerging viral diseases: Evaluating disease impact and hurdles to vaccine development,http://dx.doi.org/10.1371/journal.pntd.0006919,PMC6336248,30653504,CC BY,"Chikungunya fever (CHIKF) is an emerging infectious disease caused by an alphavirus transmitted by Aedes spp. mosquitoes. Because mosquito control programs are not highly efficient for outbreak containment, vaccines are essential to reduce the burden of disease. Although no licensed vaccine against CHIKF is yet available, many highly promising candidates are undergoing preclinical studies, and a few of them have been tested in human trials of phase 1 or 2. Here, we review recent findings regarding the need for a CHIKF vaccine and provide an update on vaccines nearing or having entered clinical trials. We also address needs to tackle bottlenecks to vaccine development—including scientific and financial barriers—and to accelerate the development of vaccines; several actions should be taken: (i) design efficacy trials to be conducted during the course of outbreaks; (ii) evaluate the opportunity for adopting the “animal rule”for demonstration of efficacy for regulatory purposes; (iii) strengthen the collective commitment of nations, international organizations, potential donors and industry; (iv) stimulate public and/or private partnerships to invest in vaccine development and licensure; and (v) identify potential markets for an effective and safe CHIKF vaccine.",2019 Jan 17,"['Rezza, Giovanni', 'Weaver, Scott C.']",PLoS Negl Trop Dis,,,True
772730b5d9f1213ae01902ca77b544cef2ba59b5,PMC,The pro-tumor effect of CD200 expression is not mimicked by agonistic CD200R antibodies,http://dx.doi.org/10.1371/journal.pone.0210796,PMC6336379,30653571,CC BY,"Tumor-infiltrating immune cells can impact tumor growth and progression. The inhibitory CD200 receptor (CD200R) suppresses the activation of myeloid cells and lack of this pathway results in a reduction of tumor growth, conversely a tumorigenic effect of CD200R triggering was also described. Here we investigated the role of CD200R activation in syngeneic mouse tumor models. We showed that agonistic CD200R antibody reached tumors, but had no significant impact on tumor growth and minor effect on infiltration of immune myeloid cells. These effects were reproduced using two different anti-CD200R clones. In contrast, we showed that CD200-deficiency did decrease melanoma tumor burden. The presence of either endogenous or tumor-expressed CD200 restored the growth of metastatic melanoma foci. On the basis of these findings, we conclude that blockade of the endogenous ligand CD200 prevented the tumorigenic effect of CD200R-expressing myeloid cells in the tumor microenvironment, whereas agonistic anti-CD200R has no effect on tumor development.",2019 Jan 17,"['Pilch, Zofia', 'Tonecka, Katarzyna', 'Skorzynski, Marcin', 'Sas, Zuzanna', 'Braniewska, Agata', 'Kryczka, Tomasz', 'Boon, Louis', 'Golab, Jakub', 'Meyaard, Linde', 'Rygiel, Tomasz P.']",PLoS One,,,True
9375f37fd1a4a949c1ec27e8b38cc3f4575dd581,PMC,A genome-wide CRISPR screen identifies N-acetylglucosamine-1-phosphate transferase as a potential antiviral target for Ebola virus,http://dx.doi.org/10.1038/s41467-018-08135-4,PMC6336797,30655525,CC BY,"There are no approved therapies for Ebola virus infection. Here, to find potential therapeutic targets, we perform a screen for genes essential for Ebola virus (EBOV) infection. We identify GNPTAB, which encodes the α and β subunits of N-acetylglucosamine-1-phosphate transferase. We show that EBOV infection of a GNPTAB knockout cell line is impaired, and that this is reversed by reconstituting GNPTAB expression. Fibroblasts from patients with mucolipidosis II, a disorder associated with mutations in GNPTAB, are refractory to EBOV, whereas cells from their healthy parents support infection. Impaired infection correlates with loss of the expression of cathepsin B, known to be essential for EBOV entry. GNPTAB activity is dependent upon proteolytic cleavage by the SKI-1/S1P protease. Inhibiting this protease with the small-molecule PF-429242 blocks EBOV entry and infection. Disruption of GNPTAB function may represent a strategy for a host-targeted therapy for EBOV.",2019 Jan 17,"['Flint, Mike', 'Chatterjee, Payel', 'Lin, David L.', 'McMullan, Laura K.', 'Shrivastava-Ranjan, Punya', 'Bergeron, Éric', 'Lo, Michael K.', 'Welch, Stephen R.', 'Nichol, Stuart T.', 'Tai, Andrew W.', 'Spiropoulou, Christina F.']",Nat Commun,,,False
dfd349a6c38da989457cc932017310cd485eea86,PMC,A genome-wide CRISPR screen identifies N-acetylglucosamine-1-phosphate transferase as a potential antiviral target for Ebola virus,http://dx.doi.org/10.1038/s41467-018-08135-4,PMC6336797,30655525,CC BY,"There are no approved therapies for Ebola virus infection. Here, to find potential therapeutic targets, we perform a screen for genes essential for Ebola virus (EBOV) infection. We identify GNPTAB, which encodes the α and β subunits of N-acetylglucosamine-1-phosphate transferase. We show that EBOV infection of a GNPTAB knockout cell line is impaired, and that this is reversed by reconstituting GNPTAB expression. Fibroblasts from patients with mucolipidosis II, a disorder associated with mutations in GNPTAB, are refractory to EBOV, whereas cells from their healthy parents support infection. Impaired infection correlates with loss of the expression of cathepsin B, known to be essential for EBOV entry. GNPTAB activity is dependent upon proteolytic cleavage by the SKI-1/S1P protease. Inhibiting this protease with the small-molecule PF-429242 blocks EBOV entry and infection. Disruption of GNPTAB function may represent a strategy for a host-targeted therapy for EBOV.",2019 Jan 17,"['Flint, Mike', 'Chatterjee, Payel', 'Lin, David L.', 'McMullan, Laura K.', 'Shrivastava-Ranjan, Punya', 'Bergeron, Éric', 'Lo, Michael K.', 'Welch, Stephen R.', 'Nichol, Stuart T.', 'Tai, Andrew W.', 'Spiropoulou, Christina F.']",Nat Commun,,,False
b5e5be4a7ee27bb1faa29832b5b20c36a903433a,PMC,A genome-wide CRISPR screen identifies N-acetylglucosamine-1-phosphate transferase as a potential antiviral target for Ebola virus,http://dx.doi.org/10.1038/s41467-018-08135-4,PMC6336797,30655525,CC BY,"There are no approved therapies for Ebola virus infection. Here, to find potential therapeutic targets, we perform a screen for genes essential for Ebola virus (EBOV) infection. We identify GNPTAB, which encodes the α and β subunits of N-acetylglucosamine-1-phosphate transferase. We show that EBOV infection of a GNPTAB knockout cell line is impaired, and that this is reversed by reconstituting GNPTAB expression. Fibroblasts from patients with mucolipidosis II, a disorder associated with mutations in GNPTAB, are refractory to EBOV, whereas cells from their healthy parents support infection. Impaired infection correlates with loss of the expression of cathepsin B, known to be essential for EBOV entry. GNPTAB activity is dependent upon proteolytic cleavage by the SKI-1/S1P protease. Inhibiting this protease with the small-molecule PF-429242 blocks EBOV entry and infection. Disruption of GNPTAB function may represent a strategy for a host-targeted therapy for EBOV.",2019 Jan 17,"['Flint, Mike', 'Chatterjee, Payel', 'Lin, David L.', 'McMullan, Laura K.', 'Shrivastava-Ranjan, Punya', 'Bergeron, Éric', 'Lo, Michael K.', 'Welch, Stephen R.', 'Nichol, Stuart T.', 'Tai, Andrew W.', 'Spiropoulou, Christina F.']",Nat Commun,,,True
ec432ab2fea7d620db7138b7c72ceecf03f09785,PMC,A genome-wide CRISPR screen identifies N-acetylglucosamine-1-phosphate transferase as a potential antiviral target for Ebola virus,http://dx.doi.org/10.1038/s41467-018-08135-4,PMC6336797,30655525,CC BY,"There are no approved therapies for Ebola virus infection. Here, to find potential therapeutic targets, we perform a screen for genes essential for Ebola virus (EBOV) infection. We identify GNPTAB, which encodes the α and β subunits of N-acetylglucosamine-1-phosphate transferase. We show that EBOV infection of a GNPTAB knockout cell line is impaired, and that this is reversed by reconstituting GNPTAB expression. Fibroblasts from patients with mucolipidosis II, a disorder associated with mutations in GNPTAB, are refractory to EBOV, whereas cells from their healthy parents support infection. Impaired infection correlates with loss of the expression of cathepsin B, known to be essential for EBOV entry. GNPTAB activity is dependent upon proteolytic cleavage by the SKI-1/S1P protease. Inhibiting this protease with the small-molecule PF-429242 blocks EBOV entry and infection. Disruption of GNPTAB function may represent a strategy for a host-targeted therapy for EBOV.",2019 Jan 17,"['Flint, Mike', 'Chatterjee, Payel', 'Lin, David L.', 'McMullan, Laura K.', 'Shrivastava-Ranjan, Punya', 'Bergeron, Éric', 'Lo, Michael K.', 'Welch, Stephen R.', 'Nichol, Stuart T.', 'Tai, Andrew W.', 'Spiropoulou, Christina F.']",Nat Commun,,,True
ef586c7c8fe46545e4d236ad74818063b1ac0c10,PMC,Systems Pharmacology Dissection of Multi-Scale Mechanisms of Action of Huo-Xiang-Zheng-Qi Formula for the Treatment of Gastrointestinal Diseases,http://dx.doi.org/10.3389/fphar.2018.01448,PMC6336928,30687082,CC BY,"Multi-components Traditional Chinese Medicine (TCM) treats various complex diseases (multi-etiologies and multi-symptoms) via herbs interactions to exert curative efficacy with less adverse effects. However, the ancient Chinese compatibility theory of herbs formula still remains ambiguous. Presently, this combination principle is dissected through a systems pharmacology study on the mechanism of action of a representative TCM formula, Huo-xiang-zheng-qi (HXZQ) prescription, on the treatment of functional dyspepsia (FD), a chronic or recurrent clinical disorder of digestive system, as typical gastrointestinal (GI) diseases which burden human physical and mental health heavily and widely. In approach, a systems pharmacology platform which incorporates the pharmacokinetic and pharmaco-dynamics evaluation, target fishing and network pharmacological analyses is employed. As a result, 132 chemicals and 48 proteins are identified as active compounds and FD-related targets, and the mechanism of HXZQ formula for the treatment of GI diseases is based on its three function modules of anti-inflammation, immune protection and gastrointestinal motility regulation mainly through four, i.e., PIK-AKT, JAK-STAT, Toll-like as well as Calcium signaling pathways. In addition, HXZQ formula conforms to the ancient compatibility rule of “Jun-Chen-Zuo-Shi” due to the different, while cooperative roles that herbs possess, specifically, the direct FD curative effects of GHX (serving as Jun drug), the anti-bacterial efficacy and major accompanying symptoms-reliving bioactivities of ZS and BZ (as Chen), the detoxication and ADME regulation capacities of GC (as Shi), as well as the minor symptoms-treating efficacy of the rest 7 herbs (as Zuo). This work not only provides an insight of the therapeutic mechanism of TCMs on treating GI diseases from a multi-scale perspective, but also may offer an efficient way for drug discovery and development from herbal medicine as complementary drugs.",2019 Jan 11,"['Zhao, Miaoqing', 'Chen, Yangyang', 'Wang, Chao', 'Xiao, Wei', 'Chen, Shusheng', 'Zhang, Shuwei', 'Yang, Ling', 'Li, Yan']",Front Pharmacol,,,True
a4a1f5c5d5bb581f195dee744257396bbbe26dd6,PMC,Focus on Translation Initiation of the HIV-1 mRNAs,http://dx.doi.org/10.3390/ijms20010101,PMC6337239,30597859,CC BY,"To replicate and disseminate, viruses need to manipulate and modify the cellular machinery for their own benefit. We are interested in translation, which is one of the key steps of gene expression and viruses that have developed several strategies to hijack the ribosomal complex. The type 1 human immunodeficiency virus is a good paradigm to understand the great diversity of translational control. Indeed, scanning, leaky scanning, internal ribosome entry sites, and adenosine methylation are used by ribosomes to translate spliced and unspliced HIV-1 mRNAs, and some require specific cellular factors, such as the DDX3 helicase, that mediate mRNA export and translation. In addition, some viral and cellular proteins, including the HIV-1 Tat protein, also regulate protein synthesis through targeting the protein kinase PKR, which once activated, is able to phosphorylate the eukaryotic translation initiation factor eIF2α, which results in the inhibition of cellular mRNAs translation. Finally, the infection alters the integrity of several cellular proteins, including initiation factors, that directly or indirectly regulates translation events. In this review, we will provide a global overview of the current situation of how the HIV-1 mRNAs interact with the host cellular environment to produce viral proteins.",2018 Dec 28,"['de Breyne, Sylvain', 'Ohlmann, Théophile']",Int J Mol Sci,,,True
9cb23e4f04ec3120b42a3c5bb0d21053f9f8a8ab,PMC,Polymerase chain reaction combined with fluorescent lateral flow immunoassay based on magnetic purification for rapid detection of canine parvovirus 2,http://dx.doi.org/10.1186/s12917-019-1774-3,PMC6337814,30654823,CC BY,"BACKGROUND: Canine parvovirus 2 (CPV-2) is one of the most common etiological agents that cause severe gastroenteritis in puppies. Early accurate diagnosis is important for infected dogs. In recent years, magnetic separation has become an efficient and useful tool for bioassays. In this study, polymerase chain reaction (PCR) combined with fluorescent lateral flow immunoassay (LFIA) based on magnetic purification assay was developed for the quantitative detection of CPV-2. RESULTS: The optimum working reaction volume and reaction time for LFIA was 100 μL and 2 min, respectively. The PCR-LFIA assay only detected CPV-2, and did not show cross-detection of non-CPV strains. Experiments showed analytical sensitivity of 3 × 10(1) copies/μL and demonstrated the PCR-LFIA has a diagnostic agreement of 100% with conventional PCR on detection of clinical samples (22.6% positive, 14/62). Cutoff value is 146. The results were further verified by sequencing and BLAST software. The entire process from PCR step only takes ~ 80 min. CONCLUSIONS: This approach provides an attractive platform for rapid and quantitative detection of CPV-2, indicating great promise as a convenient molecular detection tool to facilitate disease outbreak investigations and response timely.",2019 Jan 17,"['Zhuang, Linlin', 'Ji, Yongxin', 'Tian, Peilong', 'Wang, Kaixuan', 'Kou, Chengkun', 'Gu, Ning', 'Zhang, Yu']",BMC Vet Res,,,True
471d089defc5afd2af77f05c43b8be4cdc103bab,PMC,"IFITM Genes, Variants, and Their Roles in the Control and Pathogenesis of Viral Infections",http://dx.doi.org/10.3389/fmicb.2018.03228,PMC6338058,30687247,CC BY,"Interferon-induced transmembrane proteins (IFITMs) are a family of small proteins that localize in the plasma and endolysosomal membranes. IFITMs not only inhibit viral entry into host cells by interrupting the membrane fusion between viral envelope and cellular membranes, but also reduce the production of infectious virions or infectivity of progeny virions. Not surprisingly, some viruses can evade the restriction of IFITMs and even hijack the antiviral proteins to facilitate their infectious entry into host cells or promote the assembly of virions, presumably by modulating membrane fusion. Similar to many other host defense genes that evolve under the selective pressure of microorganism infection, IFITM genes evolved in an accelerated speed in vertebrates and many single-nucleotide polymorphisms (SNPs) have been identified in the human population, some of which have been associated with severity and prognosis of viral infection (e.g., influenza A virus). Here, we review the function and potential impact of genetic variation for IFITM restriction of viral infections. Continuing research efforts are required to decipher the molecular mechanism underlying the complicated interaction among IFITMs and viruses in an effort to determine their pathobiological roles in the context of viral infections in vivo.",2019 Jan 8,"['Zhao, Xuesen', 'Li, Jiarui', 'Winkler, Cheryl A.', 'An, Ping', 'Guo, Ju-Tao']",Front Microbiol,,,True
6f9a39f53149621828b62fd7d65513ee915ac30c,PMC,Estimating the incidence and diagnosed proportion of HIV infections in Japan: a statistical modeling study,http://dx.doi.org/10.7717/peerj.6275,PMC6338104,30671310,CC BY,"BACKGROUND: Epidemiological surveillance of HIV infection in Japan involves two technical problems for directly applying a classical backcalculation method, i.e., (i) all AIDS cases are not counted over time and (ii) people diagnosed with HIV have received antiretroviral therapy, extending the incubation period. The present study aimed to address these issues and estimate the HIV incidence and the proportion of diagnosed HIV infections, using a simple statistical model. METHODS: From among Japanese nationals, yearly incidence data of HIV diagnoses and patients with AIDS who had not previously been diagnosed as HIV positive, from 1985 to 2017, were analyzed. Using the McKendrick partial differential equation, general convolution-like equations were derived, allowing estimation of the HIV incidence and the time-dependent rate of diagnosis. A likelihood-based approach was used to obtain parameter estimates. RESULTS: Assuming that the median incubation period was 10.0 years, the cumulative number of HIV infections was estimated to be 29,613 (95% confidence interval (CI): 29,059, 30,167) by the end of 2017, and the proportion of diagnosed HIV infections was estimated at 80.3% (95% CI [78.7%–82.0%]). Allowing the median incubation period to range from 7.5 to 12.3 years, the estimate of the proportion diagnosed can vary from 77% to 84%. DISCUSSION: The proportion of diagnosed HIV infections appears to have not yet reached 90% among Japanese nationals. Compared with the peak incidence from 2005–2008, new HIV infections have clearly been in a declining trend; however, there are still more than 1,000 new HIV infections per year in Japan. To increase the diagnosed proportion of HIV infections, it is critical to identify people who have difficulty accessing consultation, testing, and care, and to explore heterogeneous patterns of infection.",2019 Jan 15,"Nishiura, Hiroshi",PeerJ,,,True
ad9cec450f3304e01cb4b517de934ba18094ce43,PMC,Molecular epidemiology of chicken anaemia virus in sick chickens in China from 2014 to 2015,http://dx.doi.org/10.1371/journal.pone.0210696,PMC6338413,30657774,CC BY,"Chicken anaemia virus (CAV), a member of the genus Gyrovirus, is the etiological agent of chicken infectious anaemia. CAV infects bone marrow-derived cells, resulting in severe anaemia and immunosuppression in young chickens and a compromised immune response in older birds. We investigated the molecular epidemiology of CAV in sick chickens in China from 2014 to 2015 and showed that the CAV-positive rate was 13.30%, in which mixed infection (55.56%) was the main type of infection. We isolated and identified 15 new CAV strains using different methods including indirect immunofluorescence assay and Western Blotting. We used overlapping polymerase chain reaction to map the whole genome of the strains. Phylogenetic analyses of the obtained sequences and related sequences available in GenBank generated four distinct groups (A–D). We built phylogenetic trees using predicted viral protein (VP) sequences. Unlike CAV VP2s and VP3s that were well conserved, the diversity of VP1s indicated that the new strains were virulent. Our epidemiological study provided new insights into the prevalence of CAV in clinical settings in recent years in China.",2019 Jan 18,"['Yao, Shuai', 'Tuo, Tianbei', 'Gao, Xiang', 'Han, Chunyan', 'Yan, Nana', 'Liu, Aijing', 'Gao, Honglei', 'Gao, Yulong', 'Cui, Hongyu', 'Liu, Changjun', 'Zhang, Yanping', 'Qi, Xiaole', 'Hussain, Altaf', 'Wang, Yongqiang', 'Wang, Xiaomei']",PLoS One,,,True
816189230d6a7194892b0f10e0dcdd3a6a025647,PMC,A new immunochromatographic assay for on-site detection of porcine epidemic diarrhea virus based on monoclonal antibodies prepared by using cell surface fluorescence immunosorbent assay,http://dx.doi.org/10.1186/s12917-019-1773-4,PMC6339306,30658643,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is a highly effective pathogen that can cause death of new-born piglet, resulting in big economical loss in pig farming industry. For rapid detection of PEDV, a new immunochromatographic assay (ICA) based on monoclonal antibodies (mAbs) was developed in this study. RESULTS: The mAbs were prepared by using PEDV positive hybridoma cells that were selected by using cell surface fluorescence immunosorbent assay (CSFIA). Fourteen mAbs against PEDV strain isolated from south of China were prepared. The optimal mAb 4A11 was coated on NC membrane as the capturing reagent and the mAb A11H7 was coupled to gold nanoparticles (AuNPs) as detection reagent for the new ICA. The new ICA was used to measure PEDV in phosphate buffer containing tween-20. Results indicated that the limit of detection (LOD) of the new ICA was 0.47 μg/mL (5.9 × 10(3) TCID(50)/mL) and the liner detection range of the ICA was 0.625–10 μg/mL (7.8 × 10(3)–10(5) TCID(50)/mL). The specificity analysis results showed that this new ICA had no cross reaction in the presence of other porcine viruses. The ICA was also validated for the detection of PEDV in swine stool samples with little interference from swine stool. To compare its accuracy to other traditional detection methods, 27 swine stool samples from south of China were investigated with the new developed ICA, commercial strip and RT-PCR. Results showed that the new ICA was more comparable to RT-PCR than commercial test strip. CONCLUSIONS: A new ICA based on mAbs prepared by CSFIA was developed in this study. It was a sensitive, specific and rapid method that could be used for on-site detection of PEDV and therefore was useful for the diagnosis and prevention of PED. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-019-1773-4) contains supplementary material, which is available to authorized users.",2019 Jan 18,"['Bian, Hongfen', 'Xu, Fei', 'Jia, Yumin', 'Wang, Lei', 'Deng, Shengchao', 'Jia, Aiqing', 'Tang, Yong']",BMC Vet Res,,,True
dedff395d93d8023667fc500d7c7c8451d581451,PMC,Antiviral activity of itraconazole against type I feline coronavirus infection,http://dx.doi.org/10.1186/s13567-019-0625-3,PMC6339390,30658691,CC BY,"Feline coronaviruses (FCoVs) are the causative agents of severe systemic disease (feline infectious peritonitis: FIP) in domestic and wild cats. FCoVs have been classified into serotypes I and II. Type I FCoV is the dominant serotype (approximately 70–90%) worldwide. Therefore, it is necessary to provide antiviral agents for type I FCoV infection. In this study, we demonstrated that itraconazole (ICZ), practically used for fungal infections in cats, inhibits the type I FCoV infection. ICZ also exhibited antiviral effect in cells after viral infection, suggesting that ICZ could potentially be used as a therapeutic.",2019 Jan 18,"['Takano, Tomomi', 'Akiyama, Misuzu', 'Doki, Tomoyoshi', 'Hohdatsu, Tsutomu']",Vet Res,,,True
de79ddbf8cff4bf83533c1c991cf5640dab43ea5,PMC,mRNA as novel technology for passive immunotherapy,http://dx.doi.org/10.1007/s00018-018-2935-4,PMC6339677,30334070,CC BY,"While active immunization elicits a lasting immune response by the body, passive immunotherapy transiently equips the body with exogenously generated immunological effectors in the form of either target-specific antibodies or lymphocytes functionalized with target-specific receptors. In either case, administration or expression of recombinant proteins plays a fundamental role. mRNA prepared by in vitro transcription (IVT) is increasingly appreciated as a drug substance for delivery of recombinant proteins. With its biological role as transient carrier of genetic information translated into protein in the cytoplasm, therapeutic application of mRNA combines several advantages. For example, compared to transfected DNA, mRNA harbors inherent safety features. It is not associated with the risk of inducing genomic changes and potential adverse effects are only temporary due to its transient nature. Compared to the administration of recombinant proteins produced in bioreactors, mRNA allows supplying proteins that are difficult to manufacture and offers extended pharmacokinetics for short-lived proteins. Based on great progress in understanding and manipulating mRNA properties, efficacy data in various models have now demonstrated that IVT mRNA constitutes a potent and flexible platform technology. Starting with an introduction into passive immunotherapy, this review summarizes the current status of IVT mRNA technology and its application to such immunological interventions.",2019 Oct 17,"['Schlake, Thomas', 'Thess, Andreas', 'Thran, Moritz', 'Jordan, Ingo']",Cell Mol Life Sci,,,True
6c3e1a43f0e199876d4bd9ff787e1911fd5cfaa6,PMC,Microbial Agents as Putative Inducers of B Cell Lymphoma in Sjögren's Syndrome through an Impaired Epigenetic Control: The State-of-The-Art,http://dx.doi.org/10.1155/2019/8567364,PMC6339763,30723750,CC BY,"INTRODUCTION: Understanding the mechanisms underlying the pathogenesis of Sjögren's syndrome (SS) is crucially important in order to be able to discriminate the steps that lead to B cell transformation and promptly identify the patients at risk of lymphomagenesis. The aim of this narrative review is to describe the evidence concerning the role that infections or dysbiosis plays in the epigenetic control of gene expression in SS patients and their possible involvement in B cell lymphomagenesis. MATERIALS AND METHODS: We searched the PubMed and Google Scholar databases and selected a total of 92 articles published during the last 25 years that describe experimental and clinical studies of the potential associations of microbiota and epigenetic aberrations with the risk of B cell lymphoma in SS patients. RESULTS AND DISCUSSION: The genetic background of SS patients is characterized by the hyperexpression of genes that are mainly involved in regulating the innate and adaptive immune responses and oncogenesis. In addition, salivary gland epithelial cells and lymphocytes both have an altered epigenetic background that enhances the activation of proinflammatory and survival pathways. Dysbiosis or chronic latent infections may tune the immune response and modify the cell epigenetic machinery in such a way as to give B lymphocytes an activated or transformed phenotype. It is also worth noting that transposable integrated retroelements may participate in the pathogenesis of SS and B cell lymphomagenesis by inducing DNA breaks, modulating cell gene expression, or generating aberrant transcripts that chronically stimulate the immune system. CONCLUSIONS: Microorganisms may epigenetically modify target cells and induce their transcriptome to generate an activated or transformed phenotype. The occurrence of lymphoma in more than 15% of SS patients may be the end result of a combination of genetics, epigenetics, and dysbiosis or latent infections.",2019 Jan 6,"['Talotta, Rossella', 'Sarzi-Puttini, Piercarlo', 'Atzeni, Fabiola']",J Immunol Res,,,True
1ed4c31d7ee724f9937c3f91d2a91b01579a853c,PMC,Chikungunya Virus Fidelity Variants Exhibit Differential Attenuation and Population Diversity in Cell Culture and Adult Mice,http://dx.doi.org/10.1128/JVI.01606-18,PMC6340026,30429348,CC BY,"Chikungunya virus (CHIKV) is a reemerging global health threat that produces debilitating arthritis in people. Like other RNA viruses with high mutation rates, CHIKV produces populations of genetically diverse genomes within a host. While several known CHIKV mutations influence disease severity in vertebrates and transmission by mosquitoes, the role of intrahost diversity in chikungunya arthritic disease has not been studied. In this study, high- and low-fidelity CHIKV variants, previously characterized by altered in vitro population mutation frequencies, were used to evaluate how intrahost diversity influences clinical disease, CHIKV replication, and antibody neutralization in immunocompetent adult mice inoculated in the rear footpads. Both high- and low-fidelity mutations were hypothesized to attenuate CHIKV arthritic disease, replication, and neutralizing antibody levels compared to wild-type (WT) CHIKV. Unexpectedly, high-fidelity mutants elicited more severe arthritic disease than the WT despite comparable CHIKV replication, whereas a low-fidelity mutant produced attenuated disease and replication. Serum antibody developed against both high- and low-fidelity CHIKV exhibited reduced neutralization of WT CHIKV. Using next-generation sequencing (NGS), the high-fidelity mutations were demonstrated to be genetically stable but produced more genetically diverse populations than WT CHIKV in mice. This enhanced diversification was subsequently reproduced after serial in vitro passage. The NGS results contrast with previously reported population diversities for fidelity variants, which focused mainly on part of the E1 gene, and highlight the need for direct measurements of mutation rates to clarify CHIKV fidelity phenotypes. IMPORTANCE CHIKV is a reemerging global health threat that elicits debilitating arthritis in humans. There are currently no commercially available CHIKV vaccines. Like other RNA viruses, CHIKV has a high mutation rate and is capable of rapid intrahost diversification during an infection. In other RNA viruses, virus population diversity associates with disease progression; however, potential impacts of intrahost viral diversity on CHIKV arthritic disease have not been studied. Using previously characterized CHIKV fidelity variants, we addressed whether CHIKV population diversity influences the severity of arthritis and host antibody response in an arthritic mouse model. Our findings show that CHIKV populations with greater genetic diversity can cause more severe disease and stimulate antibody responses with reduced neutralization of low-diversity virus populations in vitro. The discordant high-fidelity phenotypes in this study highlight the complexity of inferring replication fidelity indirectly from population diversity.",2019 Jan 17,"['Riemersma, Kasen K.', 'Steiner, Cody', 'Singapuri, Anil', 'Coffey, Lark L.']",J Virol,,,True
ff59f8566e5916d6f252eee6835b820a799642e7,PMC,Insights From Analysis of Human Antigen-Specific Memory B Cell Repertoires,http://dx.doi.org/10.3389/fimmu.2018.03064,PMC6340933,30697210,CC BY,"Memory B cells that are generated during an infection or following vaccination act as sentinels to guard against future infections. Upon repeat antigen exposure memory B cells differentiate into new antibody-secreting plasma cells to provide rapid and sustained protection. Some pathogens evade or suppress the humoral immune system, or induce memory B cells with a diminished ability to differentiate into new plasma cells. This leaves the host vulnerable to chronic or recurrent infections. Single cell approaches coupled with next generation antibody gene sequencing facilitate a detailed analysis of the pathogen-specific memory B cell repertoire. Monoclonal antibodies that are generated from antibody gene sequences allow a functional analysis of the repertoire. This review discusses what has been learned thus far from analysis of diverse pathogen-specific memory B cell compartments and describes major differences in their repertoires. Such information may illuminate ways to advance the goal of improving vaccine and therapeutic antibody design.",2019 Jan 15,"['Shah, Hemangi B.', 'Smith, Kenneth', 'Wren, Jonathan D.', 'Webb, Carol F.', 'Ballard, Jimmy D.', 'Bourn, Rebecka L.', 'James, Judith A.', 'Lang, Mark L.']",Front Immunol,,,True
03d32bf9da6495150f5016a0bf2d4b7647620c7d,PMC,Prevalence of fecal viruses and bacteriophage in Canadian farmed mink (Neovison vison),http://dx.doi.org/10.1002/mbo3.622,PMC6341152,29635866,CC BY,"Recent viral metagenomic studies have demonstrated the diversity of eukaryotic viruses and bacteriophage shed in the feces of domestic species. Although enteric disease is a major concern in the commercial mink farming industry, few etiologic agents have been well characterized. This study aimed to identify viruses shed in the fecal matter of clinically healthy commercial mink from 40 southern Ontario farms. Viral RNA was extracted from 67 pooled fecal samples (30 adult female mink and 37 kit) and amplified for Illumina sequencing on the NextSeq platform, and the resulting contigs were trimmed and assembled using Trimmomatic 0.36.0 and Spades 3.8.0 in iVirus (CyVerse, AZ, USA) and SeqMan NGen 12 (DNAStar, WI, USA). Identification of assembled sequences >100 bp (Geneious 10.1.3) showed an abundance of bacteriophage sequences, mainly from families Siphoviridae (53%), Podoviridae (22%), Myoviridae (20%), Inoviridae (1%), Leviviridae (0.04%), Tectiviridae (0.01%), and Microviridae (0.01%). A diverse range of vertebrate viruses were detected, of which posavirus 3, mink bocavirus, gyroviruses, and avian‐associated viruses were most abundant. Additionally, sequences from nonvertebrate viruses with water and soil‐associated amebal and algal hosts were also highly prevalent. The results of this study show that viruses shed in the fecal matter of healthy commercial mink are highly diverse and could be closely associated with diet, and that more research is necessary to determine how the detected viruses may impact mink health.",2018 Apr 10,"['Xie, Xiao‐Ting', 'Kropinski, Andrew M.', 'Tapscott, Brian', 'Weese, J. Scott', 'Turner, Patricia V.']",Microbiologyopen,,,True
783904b63f2c511c2ed20fdbeffc9e70d741ddd4,PMC,Prevalence of fecal viruses and bacteriophage in Canadian farmed mink (Neovison vison),http://dx.doi.org/10.1002/mbo3.622,PMC6341152,29635866,CC BY,"Recent viral metagenomic studies have demonstrated the diversity of eukaryotic viruses and bacteriophage shed in the feces of domestic species. Although enteric disease is a major concern in the commercial mink farming industry, few etiologic agents have been well characterized. This study aimed to identify viruses shed in the fecal matter of clinically healthy commercial mink from 40 southern Ontario farms. Viral RNA was extracted from 67 pooled fecal samples (30 adult female mink and 37 kit) and amplified for Illumina sequencing on the NextSeq platform, and the resulting contigs were trimmed and assembled using Trimmomatic 0.36.0 and Spades 3.8.0 in iVirus (CyVerse, AZ, USA) and SeqMan NGen 12 (DNAStar, WI, USA). Identification of assembled sequences >100 bp (Geneious 10.1.3) showed an abundance of bacteriophage sequences, mainly from families Siphoviridae (53%), Podoviridae (22%), Myoviridae (20%), Inoviridae (1%), Leviviridae (0.04%), Tectiviridae (0.01%), and Microviridae (0.01%). A diverse range of vertebrate viruses were detected, of which posavirus 3, mink bocavirus, gyroviruses, and avian‐associated viruses were most abundant. Additionally, sequences from nonvertebrate viruses with water and soil‐associated amebal and algal hosts were also highly prevalent. The results of this study show that viruses shed in the fecal matter of healthy commercial mink are highly diverse and could be closely associated with diet, and that more research is necessary to determine how the detected viruses may impact mink health.",2018 Apr 10,"['Xie, Xiao‐Ting', 'Kropinski, Andrew M.', 'Tapscott, Brian', 'Weese, J. Scott', 'Turner, Patricia V.']",Microbiologyopen,,,False
dd8386559f84e8d56f399d577d4e97529e312db5,PMC,Identfication of viral and bacterial etiologic agents of the pertussis-like syndrome in children under 5 years old hospitalized,http://dx.doi.org/10.1186/s12879-019-3671-6,PMC6341522,30665366,CC BY,"BACKGROUND: Acute respiratory infections (ARIs) represent an important cause of morbidity and mortality in children, remaining a major public health concern, especially affecting children under 5 years old from low-income countries. Unfortunately, information regarding their epidemiology is still limited in Peru. METHODS: A secondary data analysis was performed from a previous cross-sectional study conducted in children with a probable diagnosis of Pertussis from January 2010 to July 2012. All samples were analyzed via Polymerase Chain Reaction (PCR) for the following etiologies: Influenza-A, Influenza-B, RSV-A, RSV-B, Adenovirus, Parainfluenza 1 virus, Parainfluenza 2 virus, Parainfluenza 3 virus, Mycoplasma pneumoniae and Chlamydia pneumoniae. RESULTS: A total of 288 patients were included. The most common pathogen isolated was Adenovirus (49%), followed by Bordetella pertussis (41%) from our previous investigation, the most prevelant microorganisms were Mycoplasma pneumonia (26%) and Influenza-B (19.8%). Coinfections were reported in 58% of samples and the most common association was found between B. pertussis and Adenovirus (12.2%). CONCLUSIONS: There was a high prevalence of Adenovirus, Mycoplasma pneumoniae and other etiologies in patients with a probable diagnosis of pertussis. Despite the presence of persistent cough lasting at least two weeks and other clinical characteristics highly suspicious of pertussis, secondary etiologies should be considered in children under 5 years-old in order to give a proper treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-3671-6) contains supplementary material, which is available to authorized users.",2019 Jan 21,"['Saiki-Macedo, Stephanie', 'Valverde-Ezeta, Jorge', 'Cornejo-Tapia, Angela', 'Castillo, Maria Esther', 'Petrozzi-Helasvuo, Verónica', 'Aguilar-Luis, Miguel Angel', 'del Valle, Luis J.', 'Cieza-Mora, Erico', 'Bada, Carlos', 'del Aguila, Olguita', 'Silva-Caso, Wilmer', 'Martins-Luna, Johanna', 'Vasquez-Achaya, Fernando', 'del Valle-Mendoza, Juana']",BMC Infect Dis,,,True
2bdf40e784ab64290491a7b7f0dfb785c84c2082,PMC,Limiting factors for wearing personal protective equipment (PPE) in a health care environment evaluated in a randomised study,http://dx.doi.org/10.1371/journal.pone.0210775,PMC6342303,30668567,CC BY,"Pandemics and re-emerging diseases put pressure on the health care system to prepare for patient care and sample logistics requiring enhanced personnel protective equipment (PPE) for health care workers. We generated quantifiable data on ergonomics of PPE applicable in a health care setting by defining error rates and physically limiting factors due to PPE-induced restrictions. Nineteen study volunteers tested randomly allocated head- or full body-ventilated PPE suits equipped with powered-air-purifying-respirators and performed four different tasks (two laboratory tutorials, a timed test of selective attention and a test investigating reaction time, mobility, speed and physical exercise) during 6 working hours at 22°C on one day and 4 working hours at 28°C on another day. Error rates and physical parameters (fluid loss, body temperature, heart rate) were determined and ergonomic-related parameters were assessed hourly using assessment sheets. Depending on the PPE system the most restrictive factors, which however had no negative impact on performance (speed and error rate), were: reduced dexterity due to multiple glove layers, impaired visibility by flexible face shields and back pain related to the respirator of the fully ventilated suit. Heat stress and liquid loss were perceived as restrictive at a working temperature of 28°C but not 22°C.",2019 Jan 22,"['Loibner, Martina', 'Hagauer, Sandra', 'Schwantzer, Gerold', 'Berghold, Andrea', 'Zatloukal, Kurt']",PLoS One,,,True
ba3f924cd173278664082b760dccd4c6ae738436,PMC,Limiting factors for wearing personal protective equipment (PPE) in a health care environment evaluated in a randomised study,http://dx.doi.org/10.1371/journal.pone.0210775,PMC6342303,30668567,CC BY,"Pandemics and re-emerging diseases put pressure on the health care system to prepare for patient care and sample logistics requiring enhanced personnel protective equipment (PPE) for health care workers. We generated quantifiable data on ergonomics of PPE applicable in a health care setting by defining error rates and physically limiting factors due to PPE-induced restrictions. Nineteen study volunteers tested randomly allocated head- or full body-ventilated PPE suits equipped with powered-air-purifying-respirators and performed four different tasks (two laboratory tutorials, a timed test of selective attention and a test investigating reaction time, mobility, speed and physical exercise) during 6 working hours at 22°C on one day and 4 working hours at 28°C on another day. Error rates and physical parameters (fluid loss, body temperature, heart rate) were determined and ergonomic-related parameters were assessed hourly using assessment sheets. Depending on the PPE system the most restrictive factors, which however had no negative impact on performance (speed and error rate), were: reduced dexterity due to multiple glove layers, impaired visibility by flexible face shields and back pain related to the respirator of the fully ventilated suit. Heat stress and liquid loss were perceived as restrictive at a working temperature of 28°C but not 22°C.",2019 Jan 22,"['Loibner, Martina', 'Hagauer, Sandra', 'Schwantzer, Gerold', 'Berghold, Andrea', 'Zatloukal, Kurt']",PLoS One,,,True
0eecd538aac394b774221c37ddbf99eb606b96de,PMC,Limiting factors for wearing personal protective equipment (PPE) in a health care environment evaluated in a randomised study,http://dx.doi.org/10.1371/journal.pone.0210775,PMC6342303,30668567,CC BY,"Pandemics and re-emerging diseases put pressure on the health care system to prepare for patient care and sample logistics requiring enhanced personnel protective equipment (PPE) for health care workers. We generated quantifiable data on ergonomics of PPE applicable in a health care setting by defining error rates and physically limiting factors due to PPE-induced restrictions. Nineteen study volunteers tested randomly allocated head- or full body-ventilated PPE suits equipped with powered-air-purifying-respirators and performed four different tasks (two laboratory tutorials, a timed test of selective attention and a test investigating reaction time, mobility, speed and physical exercise) during 6 working hours at 22°C on one day and 4 working hours at 28°C on another day. Error rates and physical parameters (fluid loss, body temperature, heart rate) were determined and ergonomic-related parameters were assessed hourly using assessment sheets. Depending on the PPE system the most restrictive factors, which however had no negative impact on performance (speed and error rate), were: reduced dexterity due to multiple glove layers, impaired visibility by flexible face shields and back pain related to the respirator of the fully ventilated suit. Heat stress and liquid loss were perceived as restrictive at a working temperature of 28°C but not 22°C.",2019 Jan 22,"['Loibner, Martina', 'Hagauer, Sandra', 'Schwantzer, Gerold', 'Berghold, Andrea', 'Zatloukal, Kurt']",PLoS One,,,True
69bfd0fbb7ee7aab783d90ffdc58eacca258e3fc,PMC,Limiting factors for wearing personal protective equipment (PPE) in a health care environment evaluated in a randomised study,http://dx.doi.org/10.1371/journal.pone.0210775,PMC6342303,30668567,CC BY,"Pandemics and re-emerging diseases put pressure on the health care system to prepare for patient care and sample logistics requiring enhanced personnel protective equipment (PPE) for health care workers. We generated quantifiable data on ergonomics of PPE applicable in a health care setting by defining error rates and physically limiting factors due to PPE-induced restrictions. Nineteen study volunteers tested randomly allocated head- or full body-ventilated PPE suits equipped with powered-air-purifying-respirators and performed four different tasks (two laboratory tutorials, a timed test of selective attention and a test investigating reaction time, mobility, speed and physical exercise) during 6 working hours at 22°C on one day and 4 working hours at 28°C on another day. Error rates and physical parameters (fluid loss, body temperature, heart rate) were determined and ergonomic-related parameters were assessed hourly using assessment sheets. Depending on the PPE system the most restrictive factors, which however had no negative impact on performance (speed and error rate), were: reduced dexterity due to multiple glove layers, impaired visibility by flexible face shields and back pain related to the respirator of the fully ventilated suit. Heat stress and liquid loss were perceived as restrictive at a working temperature of 28°C but not 22°C.",2019 Jan 22,"['Loibner, Martina', 'Hagauer, Sandra', 'Schwantzer, Gerold', 'Berghold, Andrea', 'Zatloukal, Kurt']",PLoS One,,,False
6564f082a6c0850c1fe12262a6d060bea9fb90e4,PMC,Limiting factors for wearing personal protective equipment (PPE) in a health care environment evaluated in a randomised study,http://dx.doi.org/10.1371/journal.pone.0210775,PMC6342303,30668567,CC BY,"Pandemics and re-emerging diseases put pressure on the health care system to prepare for patient care and sample logistics requiring enhanced personnel protective equipment (PPE) for health care workers. We generated quantifiable data on ergonomics of PPE applicable in a health care setting by defining error rates and physically limiting factors due to PPE-induced restrictions. Nineteen study volunteers tested randomly allocated head- or full body-ventilated PPE suits equipped with powered-air-purifying-respirators and performed four different tasks (two laboratory tutorials, a timed test of selective attention and a test investigating reaction time, mobility, speed and physical exercise) during 6 working hours at 22°C on one day and 4 working hours at 28°C on another day. Error rates and physical parameters (fluid loss, body temperature, heart rate) were determined and ergonomic-related parameters were assessed hourly using assessment sheets. Depending on the PPE system the most restrictive factors, which however had no negative impact on performance (speed and error rate), were: reduced dexterity due to multiple glove layers, impaired visibility by flexible face shields and back pain related to the respirator of the fully ventilated suit. Heat stress and liquid loss were perceived as restrictive at a working temperature of 28°C but not 22°C.",2019 Jan 22,"['Loibner, Martina', 'Hagauer, Sandra', 'Schwantzer, Gerold', 'Berghold, Andrea', 'Zatloukal, Kurt']",PLoS One,,,False
40016692d848ec6278aacb902c921c4fde1f4d50,PMC,Limiting factors for wearing personal protective equipment (PPE) in a health care environment evaluated in a randomised study,http://dx.doi.org/10.1371/journal.pone.0210775,PMC6342303,30668567,CC BY,"Pandemics and re-emerging diseases put pressure on the health care system to prepare for patient care and sample logistics requiring enhanced personnel protective equipment (PPE) for health care workers. We generated quantifiable data on ergonomics of PPE applicable in a health care setting by defining error rates and physically limiting factors due to PPE-induced restrictions. Nineteen study volunteers tested randomly allocated head- or full body-ventilated PPE suits equipped with powered-air-purifying-respirators and performed four different tasks (two laboratory tutorials, a timed test of selective attention and a test investigating reaction time, mobility, speed and physical exercise) during 6 working hours at 22°C on one day and 4 working hours at 28°C on another day. Error rates and physical parameters (fluid loss, body temperature, heart rate) were determined and ergonomic-related parameters were assessed hourly using assessment sheets. Depending on the PPE system the most restrictive factors, which however had no negative impact on performance (speed and error rate), were: reduced dexterity due to multiple glove layers, impaired visibility by flexible face shields and back pain related to the respirator of the fully ventilated suit. Heat stress and liquid loss were perceived as restrictive at a working temperature of 28°C but not 22°C.",2019 Jan 22,"['Loibner, Martina', 'Hagauer, Sandra', 'Schwantzer, Gerold', 'Berghold, Andrea', 'Zatloukal, Kurt']",PLoS One,,,False
98e17ce4c9a1abdcba6c87d592e36be5db704d64,PMC,VAPiD: a lightweight cross-platform viral annotation pipeline and identification tool to facilitate virus genome submissions to NCBI GenBank,http://dx.doi.org/10.1186/s12859-019-2606-y,PMC6343335,30674273,CC BY,"BACKGROUND: With sequencing technologies becoming cheaper and easier to use, more groups are able to obtain whole genome sequences of viruses of public health and scientific importance. Submission of genomic data to NCBI GenBank is a requirement prior to publication and plays a critical role in making scientific data publicly available. GenBank currently has automatic prokaryotic and eukaryotic genome annotation pipelines but has no viral annotation pipeline beyond influenza virus. Annotation and submission of viral genome sequence is a non-trivial task, especially for groups that do not routinely interact with GenBank for data submissions. RESULTS: We present Viral Annotation Pipeline and iDentification (VAPiD), a portable and lightweight command-line tool for annotation and GenBank deposition of viral genomes. VAPiD supports annotation of nearly all unsegmented viral genomes. The pipeline has been validated on human immunodeficiency virus, human parainfluenza virus 1–4, human metapneumovirus, human coronaviruses (229E/OC43/NL63/HKU1/SARS/MERS), human enteroviruses/rhinoviruses, measles virus, mumps virus, Hepatitis A-E Virus, Chikungunya virus, dengue virus, and West Nile virus, as well the human polyomaviruses BK/JC/MCV, human adenoviruses, and human papillomaviruses. The program can handle individual or batch submissions of different viruses to GenBank and correctly annotates multiple viruses, including those that contain ribosomal slippage or RNA editing without prior knowledge of the virus to be annotated. VAPiD is programmed in Python and is compatible with Windows, Linux, and Mac OS systems. CONCLUSIONS: We have created a portable, lightweight, user-friendly, internet-enabled, open-source, command-line genome annotation and submission package to facilitate virus genome submissions to NCBI GenBank. Instructions for downloading and installing VAPiD can be found at https://github.com/rcs333/VAPiD.",2019 Jan 23,"['Shean, Ryan C.', 'Makhsous, Negar', 'Stoddard, Graham D.', 'Lin, Michelle J.', 'Greninger, Alexander L.']",BMC Bioinformatics,,,True
4a82252b3b4f4f90c0c0bc98ab7d817798d48c98,PMC,Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity,http://dx.doi.org/10.1371/journal.ppat.1007515,PMC6343935,30629698,CC0,"Post-translational modification of host and viral proteins by ubiquitin (Ub) and Ub-like proteins, such as interferon stimulated gene product 15 (ISG15), plays a key role in response to infection. Viruses have been increasingly identified that contain proteases possessing deubiquitinase (DUB) and/or deISGylase functions. This includes viruses in the Nairoviridae family that encode a viral homologue of the ovarian tumor protease (vOTU). vOTU activity was recently demonstrated to be critical for replication of the often-fatal Crimean-Congo hemorrhagic fever virus, with DUB activity suppressing the type I interferon responses and deISGylase activity broadly removing ISG15 conjugated proteins. There are currently about 40 known nairoviruses classified into fourteen species. Recent genomic characterization has revealed a high degree of diversity, with vOTUs showing less than 25% amino acids identities within the family. Previous investigations have been limited to only a few closely related nairoviruses, leaving it unclear what impact this diversity has on vOTU function. To probe the effects of vOTU diversity on enzyme activity and specificity, we assessed representative vOTUs spanning the Nairoviridae family towards Ub and ISG15 fluorogenic substrates. This revealed great variation in enzymatic activity and specific substrate preferences. A subset of the vOTUs were further assayed against eight biologically relevant di-Ub substrates, uncovering both common trends and distinct preferences of poly-Ub linkages by vOTUs. Four novel X-ray crystal structures were obtained that provide a biochemical rationale for vOTU substrate preferences and elucidate structural features that distinguish the vOTUs, including a motif in the Hughes orthonairovirus species that has not been previously observed in OTU domains. Additionally, structure-informed mutagenesis provided the first direct evidence of a second site involved in di-Ub binding for vOTUs. These results provide new insight into nairovirus evolution and pathogenesis, and further enhances the development of tools for therapeutic purposes.",2019 Jan 10,"['Dzimianski, John V.', 'Beldon, Brianna S.', 'Daczkowski, Courtney M.', 'Goodwin, Octavia Y.', 'Scholte, Florine E. M.', 'Bergeron, Éric', 'Pegan, Scott D.']",PLoS Pathog,,,True
3ad3e6ccff8d461f504ec161ed2069f6a97d3cda,PMC,Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity,http://dx.doi.org/10.1371/journal.ppat.1007515,PMC6343935,30629698,CC0,"Post-translational modification of host and viral proteins by ubiquitin (Ub) and Ub-like proteins, such as interferon stimulated gene product 15 (ISG15), plays a key role in response to infection. Viruses have been increasingly identified that contain proteases possessing deubiquitinase (DUB) and/or deISGylase functions. This includes viruses in the Nairoviridae family that encode a viral homologue of the ovarian tumor protease (vOTU). vOTU activity was recently demonstrated to be critical for replication of the often-fatal Crimean-Congo hemorrhagic fever virus, with DUB activity suppressing the type I interferon responses and deISGylase activity broadly removing ISG15 conjugated proteins. There are currently about 40 known nairoviruses classified into fourteen species. Recent genomic characterization has revealed a high degree of diversity, with vOTUs showing less than 25% amino acids identities within the family. Previous investigations have been limited to only a few closely related nairoviruses, leaving it unclear what impact this diversity has on vOTU function. To probe the effects of vOTU diversity on enzyme activity and specificity, we assessed representative vOTUs spanning the Nairoviridae family towards Ub and ISG15 fluorogenic substrates. This revealed great variation in enzymatic activity and specific substrate preferences. A subset of the vOTUs were further assayed against eight biologically relevant di-Ub substrates, uncovering both common trends and distinct preferences of poly-Ub linkages by vOTUs. Four novel X-ray crystal structures were obtained that provide a biochemical rationale for vOTU substrate preferences and elucidate structural features that distinguish the vOTUs, including a motif in the Hughes orthonairovirus species that has not been previously observed in OTU domains. Additionally, structure-informed mutagenesis provided the first direct evidence of a second site involved in di-Ub binding for vOTUs. These results provide new insight into nairovirus evolution and pathogenesis, and further enhances the development of tools for therapeutic purposes.",2019 Jan 10,"['Dzimianski, John V.', 'Beldon, Brianna S.', 'Daczkowski, Courtney M.', 'Goodwin, Octavia Y.', 'Scholte, Florine E. M.', 'Bergeron, Éric', 'Pegan, Scott D.']",PLoS Pathog,,,False
ccffcb8a7056d72c6e549d3a8b609805e77b259a,PMC,Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity,http://dx.doi.org/10.1371/journal.ppat.1007515,PMC6343935,30629698,CC0,"Post-translational modification of host and viral proteins by ubiquitin (Ub) and Ub-like proteins, such as interferon stimulated gene product 15 (ISG15), plays a key role in response to infection. Viruses have been increasingly identified that contain proteases possessing deubiquitinase (DUB) and/or deISGylase functions. This includes viruses in the Nairoviridae family that encode a viral homologue of the ovarian tumor protease (vOTU). vOTU activity was recently demonstrated to be critical for replication of the often-fatal Crimean-Congo hemorrhagic fever virus, with DUB activity suppressing the type I interferon responses and deISGylase activity broadly removing ISG15 conjugated proteins. There are currently about 40 known nairoviruses classified into fourteen species. Recent genomic characterization has revealed a high degree of diversity, with vOTUs showing less than 25% amino acids identities within the family. Previous investigations have been limited to only a few closely related nairoviruses, leaving it unclear what impact this diversity has on vOTU function. To probe the effects of vOTU diversity on enzyme activity and specificity, we assessed representative vOTUs spanning the Nairoviridae family towards Ub and ISG15 fluorogenic substrates. This revealed great variation in enzymatic activity and specific substrate preferences. A subset of the vOTUs were further assayed against eight biologically relevant di-Ub substrates, uncovering both common trends and distinct preferences of poly-Ub linkages by vOTUs. Four novel X-ray crystal structures were obtained that provide a biochemical rationale for vOTU substrate preferences and elucidate structural features that distinguish the vOTUs, including a motif in the Hughes orthonairovirus species that has not been previously observed in OTU domains. Additionally, structure-informed mutagenesis provided the first direct evidence of a second site involved in di-Ub binding for vOTUs. These results provide new insight into nairovirus evolution and pathogenesis, and further enhances the development of tools for therapeutic purposes.",2019 Jan 10,"['Dzimianski, John V.', 'Beldon, Brianna S.', 'Daczkowski, Courtney M.', 'Goodwin, Octavia Y.', 'Scholte, Florine E. M.', 'Bergeron, Éric', 'Pegan, Scott D.']",PLoS Pathog,,,False
b4feaed3d0aac222328559d9b3029bb3521c1a86,PMC,Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity,http://dx.doi.org/10.1371/journal.ppat.1007515,PMC6343935,30629698,CC0,"Post-translational modification of host and viral proteins by ubiquitin (Ub) and Ub-like proteins, such as interferon stimulated gene product 15 (ISG15), plays a key role in response to infection. Viruses have been increasingly identified that contain proteases possessing deubiquitinase (DUB) and/or deISGylase functions. This includes viruses in the Nairoviridae family that encode a viral homologue of the ovarian tumor protease (vOTU). vOTU activity was recently demonstrated to be critical for replication of the often-fatal Crimean-Congo hemorrhagic fever virus, with DUB activity suppressing the type I interferon responses and deISGylase activity broadly removing ISG15 conjugated proteins. There are currently about 40 known nairoviruses classified into fourteen species. Recent genomic characterization has revealed a high degree of diversity, with vOTUs showing less than 25% amino acids identities within the family. Previous investigations have been limited to only a few closely related nairoviruses, leaving it unclear what impact this diversity has on vOTU function. To probe the effects of vOTU diversity on enzyme activity and specificity, we assessed representative vOTUs spanning the Nairoviridae family towards Ub and ISG15 fluorogenic substrates. This revealed great variation in enzymatic activity and specific substrate preferences. A subset of the vOTUs were further assayed against eight biologically relevant di-Ub substrates, uncovering both common trends and distinct preferences of poly-Ub linkages by vOTUs. Four novel X-ray crystal structures were obtained that provide a biochemical rationale for vOTU substrate preferences and elucidate structural features that distinguish the vOTUs, including a motif in the Hughes orthonairovirus species that has not been previously observed in OTU domains. Additionally, structure-informed mutagenesis provided the first direct evidence of a second site involved in di-Ub binding for vOTUs. These results provide new insight into nairovirus evolution and pathogenesis, and further enhances the development of tools for therapeutic purposes.",2019 Jan 10,"['Dzimianski, John V.', 'Beldon, Brianna S.', 'Daczkowski, Courtney M.', 'Goodwin, Octavia Y.', 'Scholte, Florine E. M.', 'Bergeron, Éric', 'Pegan, Scott D.']",PLoS Pathog,,,False
fd95e7b58087917f4aa35285f3d59afc94a5b30a,PMC,Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity,http://dx.doi.org/10.1371/journal.ppat.1007515,PMC6343935,30629698,CC0,"Post-translational modification of host and viral proteins by ubiquitin (Ub) and Ub-like proteins, such as interferon stimulated gene product 15 (ISG15), plays a key role in response to infection. Viruses have been increasingly identified that contain proteases possessing deubiquitinase (DUB) and/or deISGylase functions. This includes viruses in the Nairoviridae family that encode a viral homologue of the ovarian tumor protease (vOTU). vOTU activity was recently demonstrated to be critical for replication of the often-fatal Crimean-Congo hemorrhagic fever virus, with DUB activity suppressing the type I interferon responses and deISGylase activity broadly removing ISG15 conjugated proteins. There are currently about 40 known nairoviruses classified into fourteen species. Recent genomic characterization has revealed a high degree of diversity, with vOTUs showing less than 25% amino acids identities within the family. Previous investigations have been limited to only a few closely related nairoviruses, leaving it unclear what impact this diversity has on vOTU function. To probe the effects of vOTU diversity on enzyme activity and specificity, we assessed representative vOTUs spanning the Nairoviridae family towards Ub and ISG15 fluorogenic substrates. This revealed great variation in enzymatic activity and specific substrate preferences. A subset of the vOTUs were further assayed against eight biologically relevant di-Ub substrates, uncovering both common trends and distinct preferences of poly-Ub linkages by vOTUs. Four novel X-ray crystal structures were obtained that provide a biochemical rationale for vOTU substrate preferences and elucidate structural features that distinguish the vOTUs, including a motif in the Hughes orthonairovirus species that has not been previously observed in OTU domains. Additionally, structure-informed mutagenesis provided the first direct evidence of a second site involved in di-Ub binding for vOTUs. These results provide new insight into nairovirus evolution and pathogenesis, and further enhances the development of tools for therapeutic purposes.",2019 Jan 10,"['Dzimianski, John V.', 'Beldon, Brianna S.', 'Daczkowski, Courtney M.', 'Goodwin, Octavia Y.', 'Scholte, Florine E. M.', 'Bergeron, Éric', 'Pegan, Scott D.']",PLoS Pathog,,,False
0f25721114dd6ce3e490dc43c0cd3659c70292cd,PMC,Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity,http://dx.doi.org/10.1371/journal.ppat.1007515,PMC6343935,30629698,CC0,"Post-translational modification of host and viral proteins by ubiquitin (Ub) and Ub-like proteins, such as interferon stimulated gene product 15 (ISG15), plays a key role in response to infection. Viruses have been increasingly identified that contain proteases possessing deubiquitinase (DUB) and/or deISGylase functions. This includes viruses in the Nairoviridae family that encode a viral homologue of the ovarian tumor protease (vOTU). vOTU activity was recently demonstrated to be critical for replication of the often-fatal Crimean-Congo hemorrhagic fever virus, with DUB activity suppressing the type I interferon responses and deISGylase activity broadly removing ISG15 conjugated proteins. There are currently about 40 known nairoviruses classified into fourteen species. Recent genomic characterization has revealed a high degree of diversity, with vOTUs showing less than 25% amino acids identities within the family. Previous investigations have been limited to only a few closely related nairoviruses, leaving it unclear what impact this diversity has on vOTU function. To probe the effects of vOTU diversity on enzyme activity and specificity, we assessed representative vOTUs spanning the Nairoviridae family towards Ub and ISG15 fluorogenic substrates. This revealed great variation in enzymatic activity and specific substrate preferences. A subset of the vOTUs were further assayed against eight biologically relevant di-Ub substrates, uncovering both common trends and distinct preferences of poly-Ub linkages by vOTUs. Four novel X-ray crystal structures were obtained that provide a biochemical rationale for vOTU substrate preferences and elucidate structural features that distinguish the vOTUs, including a motif in the Hughes orthonairovirus species that has not been previously observed in OTU domains. Additionally, structure-informed mutagenesis provided the first direct evidence of a second site involved in di-Ub binding for vOTUs. These results provide new insight into nairovirus evolution and pathogenesis, and further enhances the development of tools for therapeutic purposes.",2019 Jan 10,"['Dzimianski, John V.', 'Beldon, Brianna S.', 'Daczkowski, Courtney M.', 'Goodwin, Octavia Y.', 'Scholte, Florine E. M.', 'Bergeron, Éric', 'Pegan, Scott D.']",PLoS Pathog,,,False
685dca5083db2a2e85ca216e930a246108c07986,PMC,Generation of H7N9-specific human polyclonal antibodies from a transchromosomic goat (caprine) system,http://dx.doi.org/10.1038/s41598-018-36961-5,PMC6344498,30675003,CC BY,"To address the unmet needs for human polyclonal antibodies both as therapeutics and diagnostic reagents, building upon our previously established transchromosomic (Tc) cattle platform, we report herein the development of a Tc goat system expressing human polyclonal antibodies in their sera. In the Tc goat system, a human artificial chromosome (HAC) comprising the entire human immunoglobulin (Ig) gene repertoire in the germline configuration was introduced into the genetic makeup of the domestic goat. We achieved this by transferring the HAC into goat fetal fibroblast cells followed by somatic cell nuclear transfer for Tc goat production. Gene and protein expression analyses in the peripheral blood mononuclear cells (PBMC) and the sera, respectively, of Tc caprine demonstrated the successful expression of human Ig genes and antibodies. Furthermore, immunization of Tc caprine with inactivated influenza A (H7N9) viruses followed by H7N9 Hemagglutinin 1 (HA1) boosting elicited human antibodies with high neutralizing activities against H7N9 viruses in vitro. As a small ungulate, Tc caprine offers the advantages of low cost and quick establishment of herds, therefore complementing the Tc cattle platform in responses to a range of medical needs and diagnostic applications where small volumes of human antibody products are needed.",2019 Jan 23,"['Wu, Hua', 'Fan, Zhiqiang', 'Brandsrud, Michelle', 'Meng, Qinggang', 'Bobbitt, Molly', 'Regouski, Misha', 'Stott, Rusty', 'Sweat, Alexis', 'Crabtree, Jackelyn', 'Hogan, Robert J.', 'Tripp, Ralph A.', 'Wang, Zhongde', 'Polejaeva, Irina A.', 'Sullivan, Eddie J.']",Sci Rep,,,True
311aaa859b69a54fba2d8a532fcf632599002edb,PMC,"Gut Virome Analysis of Cameroonians Reveals High Diversity of Enteric Viruses, Including Potential Interspecies Transmitted Viruses",http://dx.doi.org/10.1128/mSphere.00585-18,PMC6344602,30674646,CC BY,"Diarrhea remains one of the most common causes of deaths in children. A limited number of studies have investigated the prevalence of enteric pathogens in Cameroon, and as in many other African countries, the cause of many diarrheal episodes remains unexplained. A proportion of these unknown cases of diarrhea are likely caused by yet-unidentified viral agents, some of which could be the result of (recent) interspecies transmission from animal reservoirs, like bats. Using viral metagenomics, we screened fecal samples of 221 humans (almost all with gastroenteritis symptoms) between 0 and 89 years of age with different degrees of bat contact. We identified viruses belonging to families that are known to cause gastroenteritis such as Adenoviridae, Astroviridae, Caliciviridae, Picornaviridae, and Reoviridae. Interestingly, a mammalian orthoreovirus, picobirnaviruses, a smacovirus, and a pecovirus were also found. Although there was no evidence of interspecies transmission of the most common human gastroenteritis-related viruses (Astroviridae, Caliciviridae, and Reoviridae), the phylogenies of the identified orthoreovirus, picobirnavirus, and smacovirus indicate a genetic relatedness of these viruses identified in stools of humans and those of bats and/or other animals. These findings points out the possibility of interspecies transmission or simply a shared host of these viruses (bacterial, fungal, parasitic, …) present in both animals (bats) and humans. Further screening of bat viruses in humans or vice versa will elucidate the epidemiological potential threats of animal viruses to human health. Furthermore, this study showed a huge diversity of highly divergent novel phages, thereby expanding the existing phageome considerably. IMPORTANCE Despite the availability of diagnostic tools for different enteric viral pathogens, a large fraction of human cases of gastroenteritis remains unexplained. This could be due to pathogens not tested for or novel divergent viruses of potential animal origin. Fecal virome analyses of Cameroonians showed a very diverse group of viruses, some of which are genetically related to those identified in animals. This is the first attempt to describe the gut virome of humans from Cameroon. Therefore, the data represent a baseline for future studies on enteric viral pathogens in this area and contribute to our knowledge of the world’s virome. The studies also highlight the fact that more viruses may be associated with diarrhea than the typical known ones. Hence, it provides meaningful epidemiological information on diarrhea-related viruses in this area.",2019 Jan 23,"['Yinda, Claude Kwe', 'Vanhulle, Emiel', 'Conceição-Neto, Nádia', 'Beller, Leen', 'Deboutte, Ward', 'Shi, Chenyan', 'Ghogomu, Stephen Mbigha', 'Maes, Piet', 'Van Ranst, Marc', 'Matthijnssens, Jelle']",mSphere,,,True
20c0b5aec90b16161952fc3223f317969f1c0dea,PMC,"Gut Virome Analysis of Cameroonians Reveals High Diversity of Enteric Viruses, Including Potential Interspecies Transmitted Viruses",http://dx.doi.org/10.1128/mSphere.00585-18,PMC6344602,30674646,CC BY,"Diarrhea remains one of the most common causes of deaths in children. A limited number of studies have investigated the prevalence of enteric pathogens in Cameroon, and as in many other African countries, the cause of many diarrheal episodes remains unexplained. A proportion of these unknown cases of diarrhea are likely caused by yet-unidentified viral agents, some of which could be the result of (recent) interspecies transmission from animal reservoirs, like bats. Using viral metagenomics, we screened fecal samples of 221 humans (almost all with gastroenteritis symptoms) between 0 and 89 years of age with different degrees of bat contact. We identified viruses belonging to families that are known to cause gastroenteritis such as Adenoviridae, Astroviridae, Caliciviridae, Picornaviridae, and Reoviridae. Interestingly, a mammalian orthoreovirus, picobirnaviruses, a smacovirus, and a pecovirus were also found. Although there was no evidence of interspecies transmission of the most common human gastroenteritis-related viruses (Astroviridae, Caliciviridae, and Reoviridae), the phylogenies of the identified orthoreovirus, picobirnavirus, and smacovirus indicate a genetic relatedness of these viruses identified in stools of humans and those of bats and/or other animals. These findings points out the possibility of interspecies transmission or simply a shared host of these viruses (bacterial, fungal, parasitic, …) present in both animals (bats) and humans. Further screening of bat viruses in humans or vice versa will elucidate the epidemiological potential threats of animal viruses to human health. Furthermore, this study showed a huge diversity of highly divergent novel phages, thereby expanding the existing phageome considerably. IMPORTANCE Despite the availability of diagnostic tools for different enteric viral pathogens, a large fraction of human cases of gastroenteritis remains unexplained. This could be due to pathogens not tested for or novel divergent viruses of potential animal origin. Fecal virome analyses of Cameroonians showed a very diverse group of viruses, some of which are genetically related to those identified in animals. This is the first attempt to describe the gut virome of humans from Cameroon. Therefore, the data represent a baseline for future studies on enteric viral pathogens in this area and contribute to our knowledge of the world’s virome. The studies also highlight the fact that more viruses may be associated with diarrhea than the typical known ones. Hence, it provides meaningful epidemiological information on diarrhea-related viruses in this area.",2019 Jan 23,"['Yinda, Claude Kwe', 'Vanhulle, Emiel', 'Conceição-Neto, Nádia', 'Beller, Leen', 'Deboutte, Ward', 'Shi, Chenyan', 'Ghogomu, Stephen Mbigha', 'Maes, Piet', 'Van Ranst, Marc', 'Matthijnssens, Jelle']",mSphere,,,False
c81fcf427579d337db380686325c531edba28a83,PMC,"Gut Virome Analysis of Cameroonians Reveals High Diversity of Enteric Viruses, Including Potential Interspecies Transmitted Viruses",http://dx.doi.org/10.1128/mSphere.00585-18,PMC6344602,30674646,CC BY,"Diarrhea remains one of the most common causes of deaths in children. A limited number of studies have investigated the prevalence of enteric pathogens in Cameroon, and as in many other African countries, the cause of many diarrheal episodes remains unexplained. A proportion of these unknown cases of diarrhea are likely caused by yet-unidentified viral agents, some of which could be the result of (recent) interspecies transmission from animal reservoirs, like bats. Using viral metagenomics, we screened fecal samples of 221 humans (almost all with gastroenteritis symptoms) between 0 and 89 years of age with different degrees of bat contact. We identified viruses belonging to families that are known to cause gastroenteritis such as Adenoviridae, Astroviridae, Caliciviridae, Picornaviridae, and Reoviridae. Interestingly, a mammalian orthoreovirus, picobirnaviruses, a smacovirus, and a pecovirus were also found. Although there was no evidence of interspecies transmission of the most common human gastroenteritis-related viruses (Astroviridae, Caliciviridae, and Reoviridae), the phylogenies of the identified orthoreovirus, picobirnavirus, and smacovirus indicate a genetic relatedness of these viruses identified in stools of humans and those of bats and/or other animals. These findings points out the possibility of interspecies transmission or simply a shared host of these viruses (bacterial, fungal, parasitic, …) present in both animals (bats) and humans. Further screening of bat viruses in humans or vice versa will elucidate the epidemiological potential threats of animal viruses to human health. Furthermore, this study showed a huge diversity of highly divergent novel phages, thereby expanding the existing phageome considerably. IMPORTANCE Despite the availability of diagnostic tools for different enteric viral pathogens, a large fraction of human cases of gastroenteritis remains unexplained. This could be due to pathogens not tested for or novel divergent viruses of potential animal origin. Fecal virome analyses of Cameroonians showed a very diverse group of viruses, some of which are genetically related to those identified in animals. This is the first attempt to describe the gut virome of humans from Cameroon. Therefore, the data represent a baseline for future studies on enteric viral pathogens in this area and contribute to our knowledge of the world’s virome. The studies also highlight the fact that more viruses may be associated with diarrhea than the typical known ones. Hence, it provides meaningful epidemiological information on diarrhea-related viruses in this area.",2019 Jan 23,"['Yinda, Claude Kwe', 'Vanhulle, Emiel', 'Conceição-Neto, Nádia', 'Beller, Leen', 'Deboutte, Ward', 'Shi, Chenyan', 'Ghogomu, Stephen Mbigha', 'Maes, Piet', 'Van Ranst, Marc', 'Matthijnssens, Jelle']",mSphere,,,False
3e64108a852efb10eafd287b0cb28602de94dbda,PMC,"Gut Virome Analysis of Cameroonians Reveals High Diversity of Enteric Viruses, Including Potential Interspecies Transmitted Viruses",http://dx.doi.org/10.1128/mSphere.00585-18,PMC6344602,30674646,CC BY,"Diarrhea remains one of the most common causes of deaths in children. A limited number of studies have investigated the prevalence of enteric pathogens in Cameroon, and as in many other African countries, the cause of many diarrheal episodes remains unexplained. A proportion of these unknown cases of diarrhea are likely caused by yet-unidentified viral agents, some of which could be the result of (recent) interspecies transmission from animal reservoirs, like bats. Using viral metagenomics, we screened fecal samples of 221 humans (almost all with gastroenteritis symptoms) between 0 and 89 years of age with different degrees of bat contact. We identified viruses belonging to families that are known to cause gastroenteritis such as Adenoviridae, Astroviridae, Caliciviridae, Picornaviridae, and Reoviridae. Interestingly, a mammalian orthoreovirus, picobirnaviruses, a smacovirus, and a pecovirus were also found. Although there was no evidence of interspecies transmission of the most common human gastroenteritis-related viruses (Astroviridae, Caliciviridae, and Reoviridae), the phylogenies of the identified orthoreovirus, picobirnavirus, and smacovirus indicate a genetic relatedness of these viruses identified in stools of humans and those of bats and/or other animals. These findings points out the possibility of interspecies transmission or simply a shared host of these viruses (bacterial, fungal, parasitic, …) present in both animals (bats) and humans. Further screening of bat viruses in humans or vice versa will elucidate the epidemiological potential threats of animal viruses to human health. Furthermore, this study showed a huge diversity of highly divergent novel phages, thereby expanding the existing phageome considerably. IMPORTANCE Despite the availability of diagnostic tools for different enteric viral pathogens, a large fraction of human cases of gastroenteritis remains unexplained. This could be due to pathogens not tested for or novel divergent viruses of potential animal origin. Fecal virome analyses of Cameroonians showed a very diverse group of viruses, some of which are genetically related to those identified in animals. This is the first attempt to describe the gut virome of humans from Cameroon. Therefore, the data represent a baseline for future studies on enteric viral pathogens in this area and contribute to our knowledge of the world’s virome. The studies also highlight the fact that more viruses may be associated with diarrhea than the typical known ones. Hence, it provides meaningful epidemiological information on diarrhea-related viruses in this area.",2019 Jan 23,"['Yinda, Claude Kwe', 'Vanhulle, Emiel', 'Conceição-Neto, Nádia', 'Beller, Leen', 'Deboutte, Ward', 'Shi, Chenyan', 'Ghogomu, Stephen Mbigha', 'Maes, Piet', 'Van Ranst, Marc', 'Matthijnssens, Jelle']",mSphere,,,False
9f648c48dc1e5497968b6dae614cb50db7731052,PMC,"Gut Virome Analysis of Cameroonians Reveals High Diversity of Enteric Viruses, Including Potential Interspecies Transmitted Viruses",http://dx.doi.org/10.1128/mSphere.00585-18,PMC6344602,30674646,CC BY,"Diarrhea remains one of the most common causes of deaths in children. A limited number of studies have investigated the prevalence of enteric pathogens in Cameroon, and as in many other African countries, the cause of many diarrheal episodes remains unexplained. A proportion of these unknown cases of diarrhea are likely caused by yet-unidentified viral agents, some of which could be the result of (recent) interspecies transmission from animal reservoirs, like bats. Using viral metagenomics, we screened fecal samples of 221 humans (almost all with gastroenteritis symptoms) between 0 and 89 years of age with different degrees of bat contact. We identified viruses belonging to families that are known to cause gastroenteritis such as Adenoviridae, Astroviridae, Caliciviridae, Picornaviridae, and Reoviridae. Interestingly, a mammalian orthoreovirus, picobirnaviruses, a smacovirus, and a pecovirus were also found. Although there was no evidence of interspecies transmission of the most common human gastroenteritis-related viruses (Astroviridae, Caliciviridae, and Reoviridae), the phylogenies of the identified orthoreovirus, picobirnavirus, and smacovirus indicate a genetic relatedness of these viruses identified in stools of humans and those of bats and/or other animals. These findings points out the possibility of interspecies transmission or simply a shared host of these viruses (bacterial, fungal, parasitic, …) present in both animals (bats) and humans. Further screening of bat viruses in humans or vice versa will elucidate the epidemiological potential threats of animal viruses to human health. Furthermore, this study showed a huge diversity of highly divergent novel phages, thereby expanding the existing phageome considerably. IMPORTANCE Despite the availability of diagnostic tools for different enteric viral pathogens, a large fraction of human cases of gastroenteritis remains unexplained. This could be due to pathogens not tested for or novel divergent viruses of potential animal origin. Fecal virome analyses of Cameroonians showed a very diverse group of viruses, some of which are genetically related to those identified in animals. This is the first attempt to describe the gut virome of humans from Cameroon. Therefore, the data represent a baseline for future studies on enteric viral pathogens in this area and contribute to our knowledge of the world’s virome. The studies also highlight the fact that more viruses may be associated with diarrhea than the typical known ones. Hence, it provides meaningful epidemiological information on diarrhea-related viruses in this area.",2019 Jan 23,"['Yinda, Claude Kwe', 'Vanhulle, Emiel', 'Conceição-Neto, Nádia', 'Beller, Leen', 'Deboutte, Ward', 'Shi, Chenyan', 'Ghogomu, Stephen Mbigha', 'Maes, Piet', 'Van Ranst, Marc', 'Matthijnssens, Jelle']",mSphere,,,False
7893ef5afeb48e571b8c0e088e1167898d522a0b,PMC,"Gut Virome Analysis of Cameroonians Reveals High Diversity of Enteric Viruses, Including Potential Interspecies Transmitted Viruses",http://dx.doi.org/10.1128/mSphere.00585-18,PMC6344602,30674646,CC BY,"Diarrhea remains one of the most common causes of deaths in children. A limited number of studies have investigated the prevalence of enteric pathogens in Cameroon, and as in many other African countries, the cause of many diarrheal episodes remains unexplained. A proportion of these unknown cases of diarrhea are likely caused by yet-unidentified viral agents, some of which could be the result of (recent) interspecies transmission from animal reservoirs, like bats. Using viral metagenomics, we screened fecal samples of 221 humans (almost all with gastroenteritis symptoms) between 0 and 89 years of age with different degrees of bat contact. We identified viruses belonging to families that are known to cause gastroenteritis such as Adenoviridae, Astroviridae, Caliciviridae, Picornaviridae, and Reoviridae. Interestingly, a mammalian orthoreovirus, picobirnaviruses, a smacovirus, and a pecovirus were also found. Although there was no evidence of interspecies transmission of the most common human gastroenteritis-related viruses (Astroviridae, Caliciviridae, and Reoviridae), the phylogenies of the identified orthoreovirus, picobirnavirus, and smacovirus indicate a genetic relatedness of these viruses identified in stools of humans and those of bats and/or other animals. These findings points out the possibility of interspecies transmission or simply a shared host of these viruses (bacterial, fungal, parasitic, …) present in both animals (bats) and humans. Further screening of bat viruses in humans or vice versa will elucidate the epidemiological potential threats of animal viruses to human health. Furthermore, this study showed a huge diversity of highly divergent novel phages, thereby expanding the existing phageome considerably. IMPORTANCE Despite the availability of diagnostic tools for different enteric viral pathogens, a large fraction of human cases of gastroenteritis remains unexplained. This could be due to pathogens not tested for or novel divergent viruses of potential animal origin. Fecal virome analyses of Cameroonians showed a very diverse group of viruses, some of which are genetically related to those identified in animals. This is the first attempt to describe the gut virome of humans from Cameroon. Therefore, the data represent a baseline for future studies on enteric viral pathogens in this area and contribute to our knowledge of the world’s virome. The studies also highlight the fact that more viruses may be associated with diarrhea than the typical known ones. Hence, it provides meaningful epidemiological information on diarrhea-related viruses in this area.",2019 Jan 23,"['Yinda, Claude Kwe', 'Vanhulle, Emiel', 'Conceição-Neto, Nádia', 'Beller, Leen', 'Deboutte, Ward', 'Shi, Chenyan', 'Ghogomu, Stephen Mbigha', 'Maes, Piet', 'Van Ranst, Marc', 'Matthijnssens, Jelle']",mSphere,,,False
1d82ef44c7c3dade2745cfa7419380067ba9060f,PMC,"Gut Virome Analysis of Cameroonians Reveals High Diversity of Enteric Viruses, Including Potential Interspecies Transmitted Viruses",http://dx.doi.org/10.1128/mSphere.00585-18,PMC6344602,30674646,CC BY,"Diarrhea remains one of the most common causes of deaths in children. A limited number of studies have investigated the prevalence of enteric pathogens in Cameroon, and as in many other African countries, the cause of many diarrheal episodes remains unexplained. A proportion of these unknown cases of diarrhea are likely caused by yet-unidentified viral agents, some of which could be the result of (recent) interspecies transmission from animal reservoirs, like bats. Using viral metagenomics, we screened fecal samples of 221 humans (almost all with gastroenteritis symptoms) between 0 and 89 years of age with different degrees of bat contact. We identified viruses belonging to families that are known to cause gastroenteritis such as Adenoviridae, Astroviridae, Caliciviridae, Picornaviridae, and Reoviridae. Interestingly, a mammalian orthoreovirus, picobirnaviruses, a smacovirus, and a pecovirus were also found. Although there was no evidence of interspecies transmission of the most common human gastroenteritis-related viruses (Astroviridae, Caliciviridae, and Reoviridae), the phylogenies of the identified orthoreovirus, picobirnavirus, and smacovirus indicate a genetic relatedness of these viruses identified in stools of humans and those of bats and/or other animals. These findings points out the possibility of interspecies transmission or simply a shared host of these viruses (bacterial, fungal, parasitic, …) present in both animals (bats) and humans. Further screening of bat viruses in humans or vice versa will elucidate the epidemiological potential threats of animal viruses to human health. Furthermore, this study showed a huge diversity of highly divergent novel phages, thereby expanding the existing phageome considerably. IMPORTANCE Despite the availability of diagnostic tools for different enteric viral pathogens, a large fraction of human cases of gastroenteritis remains unexplained. This could be due to pathogens not tested for or novel divergent viruses of potential animal origin. Fecal virome analyses of Cameroonians showed a very diverse group of viruses, some of which are genetically related to those identified in animals. This is the first attempt to describe the gut virome of humans from Cameroon. Therefore, the data represent a baseline for future studies on enteric viral pathogens in this area and contribute to our knowledge of the world’s virome. The studies also highlight the fact that more viruses may be associated with diarrhea than the typical known ones. Hence, it provides meaningful epidemiological information on diarrhea-related viruses in this area.",2019 Jan 23,"['Yinda, Claude Kwe', 'Vanhulle, Emiel', 'Conceição-Neto, Nádia', 'Beller, Leen', 'Deboutte, Ward', 'Shi, Chenyan', 'Ghogomu, Stephen Mbigha', 'Maes, Piet', 'Van Ranst, Marc', 'Matthijnssens, Jelle']",mSphere,,,False
58b2bd155e905053b6634ad6d2ae05901534ee3f,PMC,"Gut Virome Analysis of Cameroonians Reveals High Diversity of Enteric Viruses, Including Potential Interspecies Transmitted Viruses",http://dx.doi.org/10.1128/mSphere.00585-18,PMC6344602,30674646,CC BY,"Diarrhea remains one of the most common causes of deaths in children. A limited number of studies have investigated the prevalence of enteric pathogens in Cameroon, and as in many other African countries, the cause of many diarrheal episodes remains unexplained. A proportion of these unknown cases of diarrhea are likely caused by yet-unidentified viral agents, some of which could be the result of (recent) interspecies transmission from animal reservoirs, like bats. Using viral metagenomics, we screened fecal samples of 221 humans (almost all with gastroenteritis symptoms) between 0 and 89 years of age with different degrees of bat contact. We identified viruses belonging to families that are known to cause gastroenteritis such as Adenoviridae, Astroviridae, Caliciviridae, Picornaviridae, and Reoviridae. Interestingly, a mammalian orthoreovirus, picobirnaviruses, a smacovirus, and a pecovirus were also found. Although there was no evidence of interspecies transmission of the most common human gastroenteritis-related viruses (Astroviridae, Caliciviridae, and Reoviridae), the phylogenies of the identified orthoreovirus, picobirnavirus, and smacovirus indicate a genetic relatedness of these viruses identified in stools of humans and those of bats and/or other animals. These findings points out the possibility of interspecies transmission or simply a shared host of these viruses (bacterial, fungal, parasitic, …) present in both animals (bats) and humans. Further screening of bat viruses in humans or vice versa will elucidate the epidemiological potential threats of animal viruses to human health. Furthermore, this study showed a huge diversity of highly divergent novel phages, thereby expanding the existing phageome considerably. IMPORTANCE Despite the availability of diagnostic tools for different enteric viral pathogens, a large fraction of human cases of gastroenteritis remains unexplained. This could be due to pathogens not tested for or novel divergent viruses of potential animal origin. Fecal virome analyses of Cameroonians showed a very diverse group of viruses, some of which are genetically related to those identified in animals. This is the first attempt to describe the gut virome of humans from Cameroon. Therefore, the data represent a baseline for future studies on enteric viral pathogens in this area and contribute to our knowledge of the world’s virome. The studies also highlight the fact that more viruses may be associated with diarrhea than the typical known ones. Hence, it provides meaningful epidemiological information on diarrhea-related viruses in this area.",2019 Jan 23,"['Yinda, Claude Kwe', 'Vanhulle, Emiel', 'Conceição-Neto, Nádia', 'Beller, Leen', 'Deboutte, Ward', 'Shi, Chenyan', 'Ghogomu, Stephen Mbigha', 'Maes, Piet', 'Van Ranst, Marc', 'Matthijnssens, Jelle']",mSphere,,,False
8990b7f25eb378eebb163439eaec8401b477f1c0,PMC,"Gut Virome Analysis of Cameroonians Reveals High Diversity of Enteric Viruses, Including Potential Interspecies Transmitted Viruses",http://dx.doi.org/10.1128/mSphere.00585-18,PMC6344602,30674646,CC BY,"Diarrhea remains one of the most common causes of deaths in children. A limited number of studies have investigated the prevalence of enteric pathogens in Cameroon, and as in many other African countries, the cause of many diarrheal episodes remains unexplained. A proportion of these unknown cases of diarrhea are likely caused by yet-unidentified viral agents, some of which could be the result of (recent) interspecies transmission from animal reservoirs, like bats. Using viral metagenomics, we screened fecal samples of 221 humans (almost all with gastroenteritis symptoms) between 0 and 89 years of age with different degrees of bat contact. We identified viruses belonging to families that are known to cause gastroenteritis such as Adenoviridae, Astroviridae, Caliciviridae, Picornaviridae, and Reoviridae. Interestingly, a mammalian orthoreovirus, picobirnaviruses, a smacovirus, and a pecovirus were also found. Although there was no evidence of interspecies transmission of the most common human gastroenteritis-related viruses (Astroviridae, Caliciviridae, and Reoviridae), the phylogenies of the identified orthoreovirus, picobirnavirus, and smacovirus indicate a genetic relatedness of these viruses identified in stools of humans and those of bats and/or other animals. These findings points out the possibility of interspecies transmission or simply a shared host of these viruses (bacterial, fungal, parasitic, …) present in both animals (bats) and humans. Further screening of bat viruses in humans or vice versa will elucidate the epidemiological potential threats of animal viruses to human health. Furthermore, this study showed a huge diversity of highly divergent novel phages, thereby expanding the existing phageome considerably. IMPORTANCE Despite the availability of diagnostic tools for different enteric viral pathogens, a large fraction of human cases of gastroenteritis remains unexplained. This could be due to pathogens not tested for or novel divergent viruses of potential animal origin. Fecal virome analyses of Cameroonians showed a very diverse group of viruses, some of which are genetically related to those identified in animals. This is the first attempt to describe the gut virome of humans from Cameroon. Therefore, the data represent a baseline for future studies on enteric viral pathogens in this area and contribute to our knowledge of the world’s virome. The studies also highlight the fact that more viruses may be associated with diarrhea than the typical known ones. Hence, it provides meaningful epidemiological information on diarrhea-related viruses in this area.",2019 Jan 23,"['Yinda, Claude Kwe', 'Vanhulle, Emiel', 'Conceição-Neto, Nádia', 'Beller, Leen', 'Deboutte, Ward', 'Shi, Chenyan', 'Ghogomu, Stephen Mbigha', 'Maes, Piet', 'Van Ranst, Marc', 'Matthijnssens, Jelle']",mSphere,,,False
b4f7e950c9f485164e020d05e738c98a7cdf4b5c,PMC,"Gut Virome Analysis of Cameroonians Reveals High Diversity of Enteric Viruses, Including Potential Interspecies Transmitted Viruses",http://dx.doi.org/10.1128/mSphere.00585-18,PMC6344602,30674646,CC BY,"Diarrhea remains one of the most common causes of deaths in children. A limited number of studies have investigated the prevalence of enteric pathogens in Cameroon, and as in many other African countries, the cause of many diarrheal episodes remains unexplained. A proportion of these unknown cases of diarrhea are likely caused by yet-unidentified viral agents, some of which could be the result of (recent) interspecies transmission from animal reservoirs, like bats. Using viral metagenomics, we screened fecal samples of 221 humans (almost all with gastroenteritis symptoms) between 0 and 89 years of age with different degrees of bat contact. We identified viruses belonging to families that are known to cause gastroenteritis such as Adenoviridae, Astroviridae, Caliciviridae, Picornaviridae, and Reoviridae. Interestingly, a mammalian orthoreovirus, picobirnaviruses, a smacovirus, and a pecovirus were also found. Although there was no evidence of interspecies transmission of the most common human gastroenteritis-related viruses (Astroviridae, Caliciviridae, and Reoviridae), the phylogenies of the identified orthoreovirus, picobirnavirus, and smacovirus indicate a genetic relatedness of these viruses identified in stools of humans and those of bats and/or other animals. These findings points out the possibility of interspecies transmission or simply a shared host of these viruses (bacterial, fungal, parasitic, …) present in both animals (bats) and humans. Further screening of bat viruses in humans or vice versa will elucidate the epidemiological potential threats of animal viruses to human health. Furthermore, this study showed a huge diversity of highly divergent novel phages, thereby expanding the existing phageome considerably. IMPORTANCE Despite the availability of diagnostic tools for different enteric viral pathogens, a large fraction of human cases of gastroenteritis remains unexplained. This could be due to pathogens not tested for or novel divergent viruses of potential animal origin. Fecal virome analyses of Cameroonians showed a very diverse group of viruses, some of which are genetically related to those identified in animals. This is the first attempt to describe the gut virome of humans from Cameroon. Therefore, the data represent a baseline for future studies on enteric viral pathogens in this area and contribute to our knowledge of the world’s virome. The studies also highlight the fact that more viruses may be associated with diarrhea than the typical known ones. Hence, it provides meaningful epidemiological information on diarrhea-related viruses in this area.",2019 Jan 23,"['Yinda, Claude Kwe', 'Vanhulle, Emiel', 'Conceição-Neto, Nádia', 'Beller, Leen', 'Deboutte, Ward', 'Shi, Chenyan', 'Ghogomu, Stephen Mbigha', 'Maes, Piet', 'Van Ranst, Marc', 'Matthijnssens, Jelle']",mSphere,,,False
69c94e49590a47b77cd12156e6d8e3bd318997b6,PMC,"China’s shifting neglected parasitic infections in an era of economic reform, urbanization, disease control, and the Belt and Road Initiative",http://dx.doi.org/10.1371/journal.pntd.0006946,PMC6345419,30677027,CC BY,,2019 Jan 24,"['Wang, Lei', 'Zou, Yang', 'Zhu, Xinping', 'Bottazzi, Maria Elena', 'Hotez, Peter J.', 'Zhan, Bin']",PLoS Negl Trop Dis,,,True
72e26f33ba7ffdd2ecd34c365e6c5fc9cf424113,PMC,"Thioguanine-based DENV-2 NS2B/NS3 protease inhibitors: Virtual screening, synthesis, biological evaluation and molecular modelling",http://dx.doi.org/10.1371/journal.pone.0210869,PMC6345492,30677071,CC BY,"Dengue virus Type 2 (DENV-2) is predominant serotype causing major dengue epidemics. There are a number of studies carried out to find its effective antiviral, however to date, there is still no molecule either from peptide or small molecules released as a drug. The present study aims to identify small molecules inhibitor from National Cancer Institute database through virtual screening. One of the hits, D0713 (IC(50) = 62 μM) bearing thioguanine scaffold was derivatised into 21 compounds and evaluated for DENV-2 NS2B/NS3 protease inhibitory activity. Compounds 18 and 21 demonstrated the most potent activity with IC(50) of 0.38 μM and 16 μM, respectively. Molecular dynamics and MM/PBSA free energy of binding calculation were conducted to study the interaction mechanism of these compounds with the protease. The free energy of binding of 18 calculated by MM/PBSA is -16.10 kcal/mol compared to the known inhibitor, panduratin A (-11.27 kcal/mol), which corroborates well with the experimental observation. Results from molecular dynamics simulations also showed that both 18 and 21 bind in the active site and stabilised by the formation of hydrogen bonds with Asn174.",2019 Jan 24,"['Hariono, Maywan', 'Choi, Sy Bing', 'Roslim, Ros Fatihah', 'Nawi, Mohamed Sufian', 'Tan, Mei Lan', 'Kamarulzaman, Ezatul Ezleen', 'Mohamed, Nornisah', 'Yusof, Rohana', 'Othman, Shatrah', 'Abd Rahman, Noorsaadah', 'Othman, Rozana', 'Wahab, Habibah A.']",PLoS One,,,True
5efa53c00c644015671a7f0827caa63032940442,PMC,"Thioguanine-based DENV-2 NS2B/NS3 protease inhibitors: Virtual screening, synthesis, biological evaluation and molecular modelling",http://dx.doi.org/10.1371/journal.pone.0210869,PMC6345492,30677071,CC BY,"Dengue virus Type 2 (DENV-2) is predominant serotype causing major dengue epidemics. There are a number of studies carried out to find its effective antiviral, however to date, there is still no molecule either from peptide or small molecules released as a drug. The present study aims to identify small molecules inhibitor from National Cancer Institute database through virtual screening. One of the hits, D0713 (IC(50) = 62 μM) bearing thioguanine scaffold was derivatised into 21 compounds and evaluated for DENV-2 NS2B/NS3 protease inhibitory activity. Compounds 18 and 21 demonstrated the most potent activity with IC(50) of 0.38 μM and 16 μM, respectively. Molecular dynamics and MM/PBSA free energy of binding calculation were conducted to study the interaction mechanism of these compounds with the protease. The free energy of binding of 18 calculated by MM/PBSA is -16.10 kcal/mol compared to the known inhibitor, panduratin A (-11.27 kcal/mol), which corroborates well with the experimental observation. Results from molecular dynamics simulations also showed that both 18 and 21 bind in the active site and stabilised by the formation of hydrogen bonds with Asn174.",2019 Jan 24,"['Hariono, Maywan', 'Choi, Sy Bing', 'Roslim, Ros Fatihah', 'Nawi, Mohamed Sufian', 'Tan, Mei Lan', 'Kamarulzaman, Ezatul Ezleen', 'Mohamed, Nornisah', 'Yusof, Rohana', 'Othman, Shatrah', 'Abd Rahman, Noorsaadah', 'Othman, Rozana', 'Wahab, Habibah A.']",PLoS One,,,True
b8fe922c7cc72cd7300766f849b3bc0ddbd891fe,PMC,"Thioguanine-based DENV-2 NS2B/NS3 protease inhibitors: Virtual screening, synthesis, biological evaluation and molecular modelling",http://dx.doi.org/10.1371/journal.pone.0210869,PMC6345492,30677071,CC BY,"Dengue virus Type 2 (DENV-2) is predominant serotype causing major dengue epidemics. There are a number of studies carried out to find its effective antiviral, however to date, there is still no molecule either from peptide or small molecules released as a drug. The present study aims to identify small molecules inhibitor from National Cancer Institute database through virtual screening. One of the hits, D0713 (IC(50) = 62 μM) bearing thioguanine scaffold was derivatised into 21 compounds and evaluated for DENV-2 NS2B/NS3 protease inhibitory activity. Compounds 18 and 21 demonstrated the most potent activity with IC(50) of 0.38 μM and 16 μM, respectively. Molecular dynamics and MM/PBSA free energy of binding calculation were conducted to study the interaction mechanism of these compounds with the protease. The free energy of binding of 18 calculated by MM/PBSA is -16.10 kcal/mol compared to the known inhibitor, panduratin A (-11.27 kcal/mol), which corroborates well with the experimental observation. Results from molecular dynamics simulations also showed that both 18 and 21 bind in the active site and stabilised by the formation of hydrogen bonds with Asn174.",2019 Jan 24,"['Hariono, Maywan', 'Choi, Sy Bing', 'Roslim, Ros Fatihah', 'Nawi, Mohamed Sufian', 'Tan, Mei Lan', 'Kamarulzaman, Ezatul Ezleen', 'Mohamed, Nornisah', 'Yusof, Rohana', 'Othman, Shatrah', 'Abd Rahman, Noorsaadah', 'Othman, Rozana', 'Wahab, Habibah A.']",PLoS One,,,False
e2e0324e6e47303b20d3d9a5a476a0a652150baf,PMC,"Thioguanine-based DENV-2 NS2B/NS3 protease inhibitors: Virtual screening, synthesis, biological evaluation and molecular modelling",http://dx.doi.org/10.1371/journal.pone.0210869,PMC6345492,30677071,CC BY,"Dengue virus Type 2 (DENV-2) is predominant serotype causing major dengue epidemics. There are a number of studies carried out to find its effective antiviral, however to date, there is still no molecule either from peptide or small molecules released as a drug. The present study aims to identify small molecules inhibitor from National Cancer Institute database through virtual screening. One of the hits, D0713 (IC(50) = 62 μM) bearing thioguanine scaffold was derivatised into 21 compounds and evaluated for DENV-2 NS2B/NS3 protease inhibitory activity. Compounds 18 and 21 demonstrated the most potent activity with IC(50) of 0.38 μM and 16 μM, respectively. Molecular dynamics and MM/PBSA free energy of binding calculation were conducted to study the interaction mechanism of these compounds with the protease. The free energy of binding of 18 calculated by MM/PBSA is -16.10 kcal/mol compared to the known inhibitor, panduratin A (-11.27 kcal/mol), which corroborates well with the experimental observation. Results from molecular dynamics simulations also showed that both 18 and 21 bind in the active site and stabilised by the formation of hydrogen bonds with Asn174.",2019 Jan 24,"['Hariono, Maywan', 'Choi, Sy Bing', 'Roslim, Ros Fatihah', 'Nawi, Mohamed Sufian', 'Tan, Mei Lan', 'Kamarulzaman, Ezatul Ezleen', 'Mohamed, Nornisah', 'Yusof, Rohana', 'Othman, Shatrah', 'Abd Rahman, Noorsaadah', 'Othman, Rozana', 'Wahab, Habibah A.']",PLoS One,,,False
1343de77489ef55f903cf43a6d3732a9e8f8de98,PMC,"Thioguanine-based DENV-2 NS2B/NS3 protease inhibitors: Virtual screening, synthesis, biological evaluation and molecular modelling",http://dx.doi.org/10.1371/journal.pone.0210869,PMC6345492,30677071,CC BY,"Dengue virus Type 2 (DENV-2) is predominant serotype causing major dengue epidemics. There are a number of studies carried out to find its effective antiviral, however to date, there is still no molecule either from peptide or small molecules released as a drug. The present study aims to identify small molecules inhibitor from National Cancer Institute database through virtual screening. One of the hits, D0713 (IC(50) = 62 μM) bearing thioguanine scaffold was derivatised into 21 compounds and evaluated for DENV-2 NS2B/NS3 protease inhibitory activity. Compounds 18 and 21 demonstrated the most potent activity with IC(50) of 0.38 μM and 16 μM, respectively. Molecular dynamics and MM/PBSA free energy of binding calculation were conducted to study the interaction mechanism of these compounds with the protease. The free energy of binding of 18 calculated by MM/PBSA is -16.10 kcal/mol compared to the known inhibitor, panduratin A (-11.27 kcal/mol), which corroborates well with the experimental observation. Results from molecular dynamics simulations also showed that both 18 and 21 bind in the active site and stabilised by the formation of hydrogen bonds with Asn174.",2019 Jan 24,"['Hariono, Maywan', 'Choi, Sy Bing', 'Roslim, Ros Fatihah', 'Nawi, Mohamed Sufian', 'Tan, Mei Lan', 'Kamarulzaman, Ezatul Ezleen', 'Mohamed, Nornisah', 'Yusof, Rohana', 'Othman, Shatrah', 'Abd Rahman, Noorsaadah', 'Othman, Rozana', 'Wahab, Habibah A.']",PLoS One,,,False
7d1ced0c75fe0d918a3371354f785df10be6da7e,PMC,Characterization of a novel species of adenovirus from Japanese microbat and role of CXADR as its entry factor,http://dx.doi.org/10.1038/s41598-018-37224-z,PMC6345744,30679679,CC BY,"Recently, bat adenoviruses (BtAdVs) of genus Mastadenovirus have been isolated from various bat species, some of them displaying a wide host range in cell culture. In this study, we isolated two BtAdVs from Japanese wild microbats. While one isolate was classified as Bat mastadenovirus A, the other was phylogenetically independent of other BtAdVs. It was rather related to, but serologically different from, canine adenoviruses. We propose that the latter, isolated from Asian parti-colored bat, should be assigned to a novel species of Bat mastadenovirus. Both isolates replicated in various mammalian cell lines, implying their wide cell tropism. To gain insight into cell tropism of these BtAdVs, we investigated the coxsackievirus and adenovirus receptor (CXADR) for virus entry to the cells. We prepared CXADR-knockout canine kidney cells and found that replication of BtAdVs was significantly hampered in these cells. For confirmation, their replication in canine CXADR-addback cells was rescued to the levels with the original cells. We also found that viral replication was corrected in human or bat CXADR-transduced cells to similar levels as in canine CXADR-addback cells. These results suggest that BtAdVs were able to use several mammalian-derived CXADRs as entry factors.",2019 Jan 24,"['Kobayashi, Tomoya', 'Matsugo, Hiromichi', 'Maruyama, Junki', 'Kamiki, Haruhiko', 'Takada, Ayato', 'Maeda, Ken', 'Takenaka-Uema, Akiko', 'Tohya, Yukinobu', 'Murakami, Shin', 'Horimoto, Taisuke']",Sci Rep,,,False
17cfe7cc0c68b1002bb31a2b2afa988ab9cdc890,PMC,Characterization of a novel species of adenovirus from Japanese microbat and role of CXADR as its entry factor,http://dx.doi.org/10.1038/s41598-018-37224-z,PMC6345744,30679679,CC BY,"Recently, bat adenoviruses (BtAdVs) of genus Mastadenovirus have been isolated from various bat species, some of them displaying a wide host range in cell culture. In this study, we isolated two BtAdVs from Japanese wild microbats. While one isolate was classified as Bat mastadenovirus A, the other was phylogenetically independent of other BtAdVs. It was rather related to, but serologically different from, canine adenoviruses. We propose that the latter, isolated from Asian parti-colored bat, should be assigned to a novel species of Bat mastadenovirus. Both isolates replicated in various mammalian cell lines, implying their wide cell tropism. To gain insight into cell tropism of these BtAdVs, we investigated the coxsackievirus and adenovirus receptor (CXADR) for virus entry to the cells. We prepared CXADR-knockout canine kidney cells and found that replication of BtAdVs was significantly hampered in these cells. For confirmation, their replication in canine CXADR-addback cells was rescued to the levels with the original cells. We also found that viral replication was corrected in human or bat CXADR-transduced cells to similar levels as in canine CXADR-addback cells. These results suggest that BtAdVs were able to use several mammalian-derived CXADRs as entry factors.",2019 Jan 24,"['Kobayashi, Tomoya', 'Matsugo, Hiromichi', 'Maruyama, Junki', 'Kamiki, Haruhiko', 'Takada, Ayato', 'Maeda, Ken', 'Takenaka-Uema, Akiko', 'Tohya, Yukinobu', 'Murakami, Shin', 'Horimoto, Taisuke']",Sci Rep,,,True
47654cf27ea49e075f800ff503bbeecb4168e224,PMC,Identifying outbreaks of Porcine Epidemic Diarrhea virus through animal movements and spatial neighborhoods,http://dx.doi.org/10.1038/s41598-018-36934-8,PMC6345879,30679594,CC BY,"The spread of pathogens in swine populations is in part determined by movements of animals between farms. However, understanding additional characteristics that predict disease outbreaks and uncovering landscape factors related to between-farm spread are crucial steps toward risk mitigation. This study integrates animal movements with environmental risk factors to identify the occurrence of porcine epidemic diarrhea virus (PEDV) outbreaks. Using weekly farm-level incidence data from 332 sow farms, we applied machine-learning algorithms to quantify associations between risk factors and PEDV outbreaks with the ultimate goal of training predictive models and to identify the most important factors associated with PEDV occurrence. Our best algorithm was able to correctly predict whether an outbreak occurred during one-week periods with >80% accuracy. The most important predictors included pig movements into neighboring farms. Other important neighborhood attributes included hog density, environmental and weather factors such as vegetation, wind speed, temperature, and precipitation, and topographical features such as slope. Our neighborhood-based approach allowed us to simultaneously capture disease risks associated with long-distance animal movement as well as local spatial dynamics. The model presented here forms the foundation for near real-time disease mapping and will advance disease surveillance and control for endemic swine pathogens in the United States.",2019 Jan 24,"['Machado, Gustavo', 'Vilalta, Carles', 'Recamonde-Mendoza, Mariana', 'Corzo, Cesar', 'Torremorell, Montserrat', 'Perez, Andrez', 'VanderWaal, Kimberly']",Sci Rep,,,True
34201b73f0586cc43cf1a416647ba6fc39c35486,PMC,Mechanisms for lyssavirus persistence in non-synanthropic bats in Europe: insights from a modeling study,http://dx.doi.org/10.1038/s41598-018-36485-y,PMC6345892,30679459,CC BY,"Bats are natural reservoirs of the largest proportion of viral zoonoses among mammals, thus understanding the conditions for pathogen persistence in bats is essential to reduce human risk. Focusing on the European Bat Lyssavirus subtype 1 (EBLV-1), causing rabies disease, we develop a data-driven spatially explicit metapopulation model to investigate EBLV-1 persistence in Myotis myotis and Miniopterus schreibersii bat species in Catalonia. We find that persistence relies on host spatial structure through the migratory nature of M. schreibersii, on cross-species mixing with M. myotis, and on survival of infected animals followed by temporary immunity. The virus would not persist in the single colony of M. myotis. Our study provides for the first time epidemiological estimates for EBLV-1 progression in M. schreibersii. Our approach can be readily adapted to other zoonoses of public health concern where long-range migration and habitat sharing may play an important role.",2019 Jan 24,"['Colombi, Davide', 'Serra-Cobo, Jordi', 'Métras, Raphaëlle', 'Apolloni, Andrea', 'Poletto, Chiara', 'López-Roig, Marc', 'Bourhy, Hervé', 'Colizza, Vittoria']",Sci Rep,,,True
63aeb2ae0cf9c92c1d5b86516efc0bc748e805e7,PMC,Mechanisms for lyssavirus persistence in non-synanthropic bats in Europe: insights from a modeling study,http://dx.doi.org/10.1038/s41598-018-36485-y,PMC6345892,30679459,CC BY,"Bats are natural reservoirs of the largest proportion of viral zoonoses among mammals, thus understanding the conditions for pathogen persistence in bats is essential to reduce human risk. Focusing on the European Bat Lyssavirus subtype 1 (EBLV-1), causing rabies disease, we develop a data-driven spatially explicit metapopulation model to investigate EBLV-1 persistence in Myotis myotis and Miniopterus schreibersii bat species in Catalonia. We find that persistence relies on host spatial structure through the migratory nature of M. schreibersii, on cross-species mixing with M. myotis, and on survival of infected animals followed by temporary immunity. The virus would not persist in the single colony of M. myotis. Our study provides for the first time epidemiological estimates for EBLV-1 progression in M. schreibersii. Our approach can be readily adapted to other zoonoses of public health concern where long-range migration and habitat sharing may play an important role.",2019 Jan 24,"['Colombi, Davide', 'Serra-Cobo, Jordi', 'Métras, Raphaëlle', 'Apolloni, Andrea', 'Poletto, Chiara', 'López-Roig, Marc', 'Bourhy, Hervé', 'Colizza, Vittoria']",Sci Rep,,,True
6d2f0e8c7dd69338395c49a3e3aab7c4239766c2,PMC,A Novel Supplementation Approach to Enhance Host Response to Sublingual Vaccination,http://dx.doi.org/10.1038/s41598-018-36370-8,PMC6346055,30679470,CC BY,"Sublingual immunization is emerging as an alternative to nasal immunization and induction of mucosal IgA responses. Using Bacillus anthracis edema toxin (EdTx) as an adjuvant, we previously showed that innate responses triggered after sublingual immunization could limit generation of IgA responses. We tested whether co-administration of a neutrophil elastase inhibitor (NEI) could rescue the ability of EdTx to induce broad antibody responses, including mucosal IgA. NEI supplementation of sublingual vaccines containing EdTx promoted antigen-specific serum IgA responses but also enhanced serum IgG1, and IgG2b responses. This enhancing effect of NEI did not extend to all antibody isotypes and IgG sublclasses, since NEI  reduced serum IgE responses and did not affect IgG2a/c and IgG3 responses. NEI supplementation also promoted anti-Bacillus anthracis protective antigen (PA) neutralizing antibodies and enhanced high affinity IgG1 and IgA antibodies. In addition to serum IgA, NEI supplementation stimulated antigen-specific mucosal IgA responses in the GI tract, and enhanced antigen-specific IgG responses in vaginal washes. Analysis of CD4(+) T helper cell responses revealed that co-administration of NEI broadened the profile of cytokine responses, by stimulating Th1, Th2, Th17, and Tfh cytokines. We also noted that NEI had a higher stimulatory effect on IL-5, IL-10, IL-17 responses.",2019 Jan 24,"['Rowe, John C.', 'Attia, Zayed', 'Kim, Eunsoo', 'Cormet-Boyaka, Estelle', 'Boyaka, Prosper N.']",Sci Rep,,,True
8b25bae266584f12c3b5af9e5cf3e81c84808c36,PMC,Interferon-induced transmembrane protein 3 blocks fusion of sensitive but not resistant viruses by partitioning into virus-carrying endosomes,http://dx.doi.org/10.1371/journal.ppat.1007532,PMC6347298,30640957,CC BY,"Late endosome-resident interferon-induced transmembrane protein 3 (IFITM3) inhibits fusion of diverse viruses, including Influenza A virus (IAV), by a poorly understood mechanism. Despite the broad antiviral activity of IFITM3, viruses like Lassa virus (LASV), are fully resistant to its inhibitory effects. It is currently unclear whether resistance arises from a highly efficient fusion machinery that is capable of overcoming IFITM3 restriction or the ability to enter from cellular sites devoid of this factor. Here, we constructed and validated a functional IFITM3 tagged with EGFP or other fluorescent proteins. This breakthrough allowed live cell imaging of virus co-trafficking and fusion with endosomal compartments in cells expressing fluorescent IFITM3. Three-color single virus and endosome tracking revealed that sensitive (IAV), but not resistant (LASV), viruses become trapped within IFITM3-positive endosomes where they underwent hemifusion but failed to release their content into the cytoplasm. IAV fusion with IFITM3-containing compartments could be rescued by amphotericin B treatment, which has been previously shown to antagonize the antiviral activity of this protein. By comparison, virtually all LASV particles trafficked and fused with endosomes lacking detectable levels of fluorescent IFITM3, implying that this virus escapes restriction by utilizing endocytic pathways that are distinct from the IAV entry pathways. The importance of virus uptake and transport pathways is further reinforced by the observation that LASV glycoprotein-mediated cell-cell fusion is inhibited by IFITM3 and other members of the IFITM family expressed in target cells. Together, our results strongly support a model according to which IFITM3 accumulation at the sites of virus fusion is a prerequisite for its antiviral activity and that this protein traps viral fusion at a hemifusion stage by preventing the formation of fusion pores. We conclude that the ability to utilize alternative endocytic pathways for entry confers IFITM3-resistance to otherwise sensitive viruses.",2019 Jan 14,"['Suddala, Krishna C.', 'Lee, Christine C.', 'Meraner, Paul', 'Marin, Mariana', 'Markosyan, Ruben M.', 'Desai, Tanay M.', 'Cohen, Fredric S.', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,True
92a27720f4fce8715f405895fc5e7633b096acf5,PMC,"Insights From Deep Sequencing of the HBV Genome—Unique, Tiny, and Misunderstood",http://dx.doi.org/10.1053/j.gastro.2018.07.058,PMC6347571,30268787,CC BY,"Hepatitis B virus (HBV) is a unique, tiny, partially double-stranded, reverse-transcribing DNA virus with proteins encoded by multiple overlapping reading frames. The substitution rate is surprisingly high for a DNA virus, but lower than that of other reverse transcribing organisms. More than 260 million people worldwide have chronic HBV infection, which causes 0.8 million deaths a year. Because of the high burden of disease, international health agencies have set the goal of eliminating HBV infection by 2030. Nonetheless, the intriguing HBV genome has not been well characterized. We summarize data on the HBV genome structure and replication cycle, explain and quantify diversity within and among infected individuals, and discuss advances that can be offered by application of next-generation sequencing technology. In-depth HBV genome analyses could increase our understanding of disease pathogenesis and allow us to better predict patient outcomes, optimize treatment, and develop new therapeutics.",2019 Jan,"['McNaughton, Anna L.', 'D’Arienzo, Valentina', 'Ansari, M. Azim', 'Lumley, Sheila F.', 'Littlejohn, Margaret', 'Revill, Peter', 'McKeating, Jane A.', 'Matthews, Philippa C.']",Gastroenterology,,,False
350bf76f2ecfc9322c9c8b59af3b7a14a6e51c0f,PMC,Analysis of pig trading networks and practices in Uganda,http://dx.doi.org/10.1007/s11250-018-1668-6,PMC6347582,30073452,CC BY,"East Africa is undergoing rapid expansion of pig rearing, driven by increasing pork consumption. Introduction and expansion of pig production systems in this biodiverse landscape may create new risks, including zoonotic pathogen transmission. Historically, biosecurity measures have primarily been focused at farm level, ignoring the important function pig traders fulfill between farmers and consumers. This study interviewed pig traders operating at Uganda’s only registered pork abattoir to describe their characteristics, business practices, biosecurity practices, and pig health management and reporting practices. All the traders were male, and nearly all (90.5%) relied on pig trading as their primary source of income. Most of the pigs brought for processing at the slaughterhouse were purchased from smallholder farms (87.3%). In addition, there was a significant difference in the high price paid per kilogram at farm gate by region (P = 0.005). High prices paid at farm gate were associated with holiday periods (P < 0.001), harvest season (P < 0.001), and drought (P < 0.001). Traders preferred buying live pigs from male farmers (88.9%) because they were considered the final decision makers and owned the pigs being sold. All pig traders were aware of clinical signs indicating a pig was sick. This study has provided baseline information on pig trader practices in Uganda. Improvements in local pork slaughterhouses and markets will benefit not only pig traders in accessing consistent customers but also individual pig farmers by increasing their market access. Finally, given their role as a link between farmers and consumers, traders would benefit from targeted inclusion in disease control and prevention strategies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11250-018-1668-6) contains supplementary material, which is available to authorized users.",2019 Aug 2,"['Atherstone, C.', 'Galiwango, R. G.', 'Grace, D.', 'Alonso, S.', 'Dhand, N. K.', 'Ward, M. P.', 'Mor, S. M.']",Trop Anim Health Prod,,,True
21e12783ad4aac6ecf757de6c644368ad999cd58,PMC,Nonconventional opponents: a review of malaria and leishmaniasis among United States Armed Forces,http://dx.doi.org/10.7717/peerj.6313,PMC6348955,30701136,CC BY,"As the United States military engage with different countries and cultures throughout the world, personnel become exposed to new biospheres as well. There are many infectious pathogens that are not endemic to the US, but two of particular importance are Plasmodium and Leishmania, which respectively cause malaria and leishmaniasis. These parasites are both known to cause significant disease burden in their endemic locales, and thus pose a threat to military travelers. This review introduces readers to basic life cycle and disease mechanisms for each. Local and military epidemiology are described, as are the specific actions taken by the US military for prevention and treatment purposes. Complications of such measures with regard to human health are also discussed, including possible chemical toxicities. Additionally, poor recognition of these diseases upon an individual’s return leading to complications and treatment delays in the United States are examined. Information about canine leishmaniasis, poorly studied relative to its human manifestation, but of importance due to the utilization of dogs in military endeavors is presented. Future implications for the American healthcare system regarding malaria and leishmaniasis are also presented.",2019 Jan 25,"['Beiter, Kaylin J.', 'Wentlent, Zachariah J.', 'Hamouda, Adrian R.', 'Thomas, Bolaji N.']",PeerJ,,,True
937d7695ba3f5f31a54eef142d6865c6460d5032,PMC,IL‐17A contributes to HSV1 infection‐induced acute lung injury in a mouse model of pulmonary fibrosis,http://dx.doi.org/10.1111/jcmm.13992,PMC6349191,30378252,CC BY,"BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) often experience acute exacerbation (AE) after an episode of common cold. AIMS: To establish a mouse model of virus infection‐induced AE‐IPF and investigate the mechanism underlying the AE‐IPF. METHODS: Herpes simplex virus 1 (HSV1) was inoculated intranasally to wild‐type (WT) and IL‐17A gene knockout (IL‐17A(‐/‐)) mice 21 days after intratracheal administration of bleomycin (BLM). RESULTS: HSV1 infection caused acute exacerbation in mice with BLM‐induced fibrosis. Compared with the BLM+Saline mice, the mice with BLM+HSV1 showed significantly higher acute lung injury (ALI) score (P < 0.0001), lower survival rate (100% vs 21.4%, P < 0.0001), poorer lung function and higher inflammatory response representing by increased total inflammatory cells in bronchoalveolar lavage fluid (BALF) (P = 0.0323), increased proportion of Th17 cells in peripheral blood (P = 0.0004) and higher inflammatory factors in BALF. In addition, HSV1 infection increased the expression of endoplasmic reticulum stress (ERS)‐related proteins in mice with BLM‐induced fibrosis. The inhibition of ERS by tauroursodeoxycholic acid (TUDCA, an ERS inhibitor) significantly reduced the IL‐17A levels in BALF (P = 0.0140) and TH17 cells in the peripheral blood (P = 0.0084) of mice with BLM+HSV1, suggesting that suppression of ERS may reduce TH17 response in mice with AE‐IPF. Compared with WT mice with BLM+HSV1, IL‐17A(‐/‐) mice with BLM+HSV1 had lower ALI score (P = 0.0119), higher survival rate (78.6% vs 21.4%, P = 0.004), improved lung function, and milder inflammatory response. CONCLUSIONS: HSV1 infection in addition to BLM‐induced IPF can successfully establish AE‐IPF in mice. IL‐17A and ERS promote lung inflammation in AE‐IPF development.",2019 Feb 30,"['Chen, Tao', 'Qiu, Hui', 'Zhao, Meng‐Meng', 'Chen, Shan‐Shan', 'Wu, Qin', 'Zhou, Nian‐Yu', 'Lu, Li‐Qin', 'Song, Jia‐Cui', 'Tang, Dan‐Li', 'Weng, Dong', 'Li, Hui‐Ping']",J Cell Mol Med,,,True
fc58f48d9ac1d492c691a36eb76e377442dc149a,PMC,Involvement of PRRSV NSP3 and NSP5 in the autophagy process,http://dx.doi.org/10.1186/s12985-019-1116-x,PMC6350329,30691473,CC BY,"BACKGROUND: Autophagy is an essential process in eukaryotic cells in which autophagosomes form to deliver cellular organelles and long-lived proteins to lysosomes for degradation. Many studies have recently identified the regulatory mechanisms involved in the interaction between viral infection and autophagy. METHODS: LC3 turnover and the proteins in the endoplasmic reticulum (ER) stress pathway were investigated using western blot analysis. The formation and degradation of autophagosomes were detected using immunofluorescence staining. RESULTS: Autophagy was activated by porcine reproductive and respiratory syndrome virus (PRRSV) NSP3, NSP5 and NSP9, which are two transmembrane proteins and an RNA-dependent RNA polymerase, respectively. The formation of autophagosomes was induced by NSP3 and NSP5 and developed from the ER; the fusion of these autophagosomes with lysosomes was limited. Although NSP3 and NSP5 are ER transmembrane proteins, these proteins did not activate the ER stress signaling pathways. In addition, the cytoplasmic domain of NSP3 plays a pivotal role in activating autophagy. CONCLUSIONS: The data presented in this study reveal an important relationship between PRRSV NSPs and autophagy and provide new insights that improve our understanding of the involvement of PRRSV NSPs in the autophagy process. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-019-1116-x) contains supplementary material, which is available to authorized users.",2019 Jan 28,"['Zhang, Wei', 'Chen, Keren', 'Guo, Yang', 'Chen, Yaosheng', 'Liu, Xiaohong']",Virol J,,,True
ed8cb0477be53b0ffb5ebf65d4dd46453be053b2,PMC,Serologic Markers for Ebolavirus Among Healthcare Workers in the Democratic Republic of the Congo,http://dx.doi.org/10.1093/infdis/jiy499,PMC6350949,30239838,CC BY,"Healthcare settings have played a major role in propagation of Ebola virus (EBOV) outbreaks. Healthcare workers (HCWs) have elevated risk of contact with EBOV-infected patients, particularly if safety precautions are not rigorously practiced. We conducted a serosurvey to determine seroprevalence against multiple EBOV antigens among HCWs of Boende Health Zone, Democratic Republic of the Congo, the site of a 2014 EBOV outbreak. Interviews and specimens were collected from 565 consenting HCWs. Overall, 234 (41.4%) of enrolled HCWs were reactive to at least 1 EBOV protein: 159 (28.1%) were seroreactive for anti-glycoprotein immunoglobulin G (IgG), 89 (15.8%) were seroreactive for anti-nucleoprotein IgG, and 54 (9.5%) were VP40 positive. Additionally, sera from 16 (2.8%) HCWs demonstrated neutralization capacity. These data demonstrate that a significant proportion of HCWs have the ability to neutralize virus, despite never having developed Ebola virus disease symptoms, highlighting an important and poorly documented aspect of EBOV infection and progression.",2019 Feb 15,"['Hoff, Nicole A', 'Mukadi, Patrick', 'Doshi, Reena H', 'Bramble, Matthew S', 'Lu, Kai', 'Gadoth, Adva', 'Sinai, Cyrus', 'Spencer, D’Andre', 'Nicholson, Bradley P', 'Williams, Russell', 'Mossoko, Matthias', 'Ilunga-Kebela, Benoit', 'Wasiswa, Joseph', 'Okitolonda-Wemakoy, Emile', 'Alfonso, Vivian H', 'Steffen, Imke', 'Muyembe-Tamfum, Jean-Jacques', 'Simmons, Graham', 'Rimoin, Anne W']",J Infect Dis,,,True
e67eb3bd9090630fa37b601957ed1dcc088901cf,PMC,Advancements in Nucleic Acid Based Therapeutics against Respiratory Viral Infections,http://dx.doi.org/10.3390/jcm8010006,PMC6351902,30577479,CC BY,"Several viruses cause pulmonary infections due to their shared tropism with cells of the respiratory tract. These respiratory problems due to viral infection become a public health concern due to rapid transmission through air/aerosols or via direct-indirect contact with infected persons. In addition, the cross-species transmission causes alterations to viral genetic makeup thereby increasing the risk of emergence of pathogens with new and more potent infectivity. With the introduction of effective nucleic acid-based technologies, post translational gene silencing (PTGS) is being increasingly used to silence viral gene targets and has shown promising approach towards management of many viral infections. Since several host factors are also utilized by these viruses during various stages of infection, silencing these host factors can also serve as promising therapeutic tool. Several nucleic acid-based technologies such as short interfering RNAs (siRNA), antisense oligonucleotides, aptamers, deoxyribozymes (DNAzymes), and ribozymes have been studied and used against management of respiratory viruses. These therapeutic nucleic acids can be efficiently delivered through the airways. Studies have also shown efficacy of gene therapy in clinical trials against respiratory syncytial virus (RSV) as well as models of respiratory diseases including severe acute respiratory syndrome (SARS), measles and influenza. In this review, we have summarized some of the recent advancements made in the area of nucleic acid based therapeutics and highlighted the emerging roles of nucleic acids in the management of some of the severe respiratory viral infections. We have also focused on the methods of their delivery and associated challenges.",2018 Dec 20,"['Asha, Kumari', 'Kumar, Prashant', 'Sanicas, Melvin', 'Meseko, Clement A.', 'Khanna, Madhu', 'Kumar, Binod']",J Clin Med,,,True
ab2dc5037a08c6bab002949e27839054d0ff87bf,PMC,"Genomic sequence of yellow fever virus from a Dutch traveller returning from the Gambia-Senegal region, the Netherlands, November 2018",http://dx.doi.org/10.2807/1560-7917.ES.2019.24.4.1800684,PMC6351999,30696531,CC BY,"In November 2018, yellow fever was diagnosed in a Dutch traveller returning from a bicycle tour in the Gambia-Senegal region. A complete genome sequence of yellow fever virus (YFV) from the case was generated and clustered phylogenetically with YFV from the Gambia and Senegal, ruling out importation into the Netherlands from recent outbreaks in Brazil or Angola. We emphasise the need for increased public awareness of YFV vaccination before travelling to endemic countries.",2019 Jan 24,"['Phan, My VT', 'Murad, Sarwa Darwish', 'van der Eijk, Annemiek A', 'Metselaar, Herold J.', 'Hartog, Hermien', 'Harinck, Femme', 'GeurtsvanKessel, Corine H', 'Molenkamp, Richard', 'Cotten, Matthew', 'Koopmans, Marion PG']",Euro Surveill,,,True
9834386da0ccac785aad715b6fc38e3123d8afc8,PMC,"Analysis of Epidemiological Characteristics of Notifiable Diseases Reported in Children Aged 0–14 Years from 2008 to 2017 in Zhejiang Province, China",http://dx.doi.org/10.3390/ijerph16020168,PMC6352024,30634443,CC BY,"This study aims to learn the characteristics of morbidity and mortality of notifiable diseases reported in children aged 0–14 years in Zhejiang Province in 2008–2017. We collated data from the China Information System for Disease Control and Prevention in Zhejiang province between 1 January 2008 and 31 December 2017 of children aged 0–14 years. From 2008 to 2017, a total of 32 types and 1,994,740 cases of notifiable diseases were reported in children aged 0–14 years, including 266 deaths in Zhejiang Province. The annual average morbidity was 2502.87/100,000, and the annual average mortality was 0.33/100,000. Male morbidity was 2886.98/100,000, and female morbidity was 2072.16/100,000, with the male morbidity rate higher than the female morbidity rate (χ(2) = 54,033.12, p < 0.01). No Class A infectious diseases were reported. The morbidity of Class B infectious diseases showed a downward trend, but that of Class C infectious diseases showed an upward trend. There were 72,041 cases in 22 kinds of Class B infectious disease and 138 death cases, with a morbidity rate of 90.39/100,000, and a mortality rate of 0.17/100,000. There were 1,922,699 cases in 10 kinds of Class C infectious disease and 128 death cases, with a morbidity rate of 2412.47/100,000, and a mortality rate of 0.16/100,000. The main high-prevalence diseases included hand-foot-and-mouth disease (1430.38/100,000), other infectious diarrheal diseases (721.40/100,000), mumps (168.83/100,000), and influenza (47.40/100,000). We should focus on the prevention and control of hand-foot and mouth disease, other infectious diarrheal diseases, mumps and influenza in children aged 0–14 years in Zhejiang Province. It is recommended to strengthen epidemic surveillance and undertake early prevention and control measures in order to reduce the younger children incidence rate of infectious diseases. Immunization planning vaccines can help achieve a significant preventive decline of infectious diseases.",2019 Jan 9,"['Lu, Qinbao', 'Ding, Zheyuan', 'Wu, Chen', 'Wu, Haocheng', 'Lin, Junfen']",Int J Environ Res Public Health,,,True
84737ac767f2be6c8623fb433c75e0fa5faf95b0,PMC,Serial Multiple Mediation Analyses: How to Enhance Individual Public Health Emergency Preparedness and Response to Environmental Disasters,http://dx.doi.org/10.3390/ijerph16020223,PMC6352079,30646637,CC BY,"Recent environmental disasters have revealed the government’s limitations in real-time response and mobilization to help the public, especially when disasters occur in large areas at the same time. Therefore, enhancing the ability to prepare for public health emergencies at the grassroots level and extend public health emergency response mechanisms to communities, and even to individual families, is a research question that is of practical significance. This study aimed to investigate mechanisms to determine how media exposure affects individual public health emergency preparedness (PHEP) to environmental disasters; specifically, we examined the mediating role of knowledge and trust in government. The results were as follows: (1) knowledge had a significant mediating effect on the relationship between media exposure and PHEP; (2) trust in government had a significant mediating effect on the relationship between media exposure and PHEP; (3) knowledge and trust in government had significant multiple mediating effects on the relationship between media exposure and PHEP.",2019 Jan 14,"['Hong, Yuxiang', 'Lee, Taesam', 'Kim, Jong-Suk']",Int J Environ Res Public Health,,,True
25b2a50598fe741c4092ca239bacca5e72e79972,PMC,A Review and Update on Waterborne Viral Diseases Associated with Swimming Pools,http://dx.doi.org/10.3390/ijerph16020166,PMC6352248,30634384,CC BY,"Infectious agents, including bacteria, viruses, protozoa, and molds, may threaten the health of swimming pool bathers. Viruses are a major cause of recreationally-associated waterborne diseases linked to pools, lakes, ponds, thermal pools/spas, rivers, and hot springs. They can make their way into waters through the accidental release of fecal matter, body fluids (saliva, mucus), or skin flakes by symptomatic or asymptomatic carriers. We present an updated overview of epidemiological data on viral outbreaks, a project motivated, among other things, by the availability of improved viral detection methodologies. Special attention is paid to outbreak investigations (source of the outbreak, pathways of transmission, chlorination/disinfection). Epidemiological studies on incidents of viral contamination of swimming pools under non-epidemic conditions are also reviewed.",2019 Jan 9,"['Bonadonna, Lucia', 'La Rosa, Giuseppina']",Int J Environ Res Public Health,,,True
f5e8e27a130f3239cafe592f4174b290849b0f2f,PMC,Innate Immune Responses and Viral-Induced Neurologic Disease,http://dx.doi.org/10.3390/jcm8010003,PMC6352557,30577473,CC BY,"Multiple sclerosis (MS) is a disease of the central nervous system (CNS) characterized by chronic neuroinflammation, axonal damage, and demyelination. Cellular components of the adaptive immune response are viewed as important in initiating formation of demyelinating lesions in MS patients. This notion is supported by preclinical animal models, genome-wide association studies (GWAS), as well as approved disease modifying therapies (DMTs) that suppress clinical relapse and are designed to impede infiltration of activated lymphocytes into the CNS. Nonetheless, emerging evidence demonstrates that the innate immune response e.g., neutrophils can amplify white matter damage through a variety of different mechanisms. Indeed, using a model of coronavirus-induced neurologic disease, we have demonstrated that sustained neutrophil infiltration into the CNS of infected animals correlates with increased demyelination. This brief review highlights recent evidence arguing that targeting the innate immune response may offer new therapeutic avenues for treatment of demyelinating disease including MS.",2018 Dec 20,"['Cheng, Yuting', 'Skinner, Dominic D.', 'Lane, Thomas E.']",J Clin Med,,,True
390b4e40d86e389acf5cb47705c7c02eca264c8a,PMC,Nanoparticle-Based Vaccines Against Respiratory Viruses,http://dx.doi.org/10.3389/fimmu.2019.00022,PMC6353795,30733717,CC BY,"The respiratory mucosa is the primary portal of entry for numerous viruses such as the respiratory syncytial virus, the influenza virus and the parainfluenza virus. These pathogens initially infect the upper respiratory tract and then reach the lower respiratory tract, leading to diseases. Vaccination is an affordable way to control the pathogenicity of viruses and constitutes the strategy of choice to fight against infections, including those leading to pulmonary diseases. Conventional vaccines based on live-attenuated pathogens present a risk of reversion to pathogenic virulence while inactivated pathogen vaccines often lead to a weak immune response. Subunit vaccines were developed to overcome these issues. However, these vaccines may suffer from a limited immunogenicity and, in most cases, the protection induced is only partial. A new generation of vaccines based on nanoparticles has shown great potential to address most of the limitations of conventional and subunit vaccines. This is due to recent advances in chemical and biological engineering, which allow the design of nanoparticles with a precise control over the size, shape, functionality and surface properties, leading to enhanced antigen presentation and strong immunogenicity. This short review provides an overview of the advantages associated with the use of nanoparticles as vaccine delivery platforms to immunize against respiratory viruses and highlights relevant examples demonstrating their potential as safe, effective and affordable vaccines.",2019 Jan 24,"['Al-Halifa, Soultan', 'Gauthier, Laurie', 'Arpin, Dominic', 'Bourgault, Steve', 'Archambault, Denis']",Front Immunol,,,True
d4766bca29ba8c705eed4b4a721476ccf300fa21,PMC,Resistance to coronavirus infection in amino peptidase N-deficient pigs,http://dx.doi.org/10.1007/s11248-018-0100-3,PMC6353812,30315482,CC BY,"The alphacoronaviruses, transmissible gastroenteritis virus (TGEV) and Porcine epidemic diarrhea virus (PEDV) are sources of high morbidity and mortality in neonatal pigs, a consequence of dehydration caused by the infection and necrosis of enterocytes. The biological relevance of amino peptidase N (ANPEP) as a putative receptor for TGEV and PEDV in pigs was evaluated by using CRISPR/Cas9 to edit exon 2 of ANPEP resulting in a premature stop codon. Knockout pigs possessing the null ANPEP phenotype and age matched wild type pigs were challenged with either PEDV or TGEV. Fecal swabs were collected daily from each animal beginning 1 day prior to challenge with PEDV until the termination of the study. The presence of virus nucleic acid was determined by PCR. ANPEP null pigs did not support infection with TGEV, but retained susceptibility to infection with PEDV. Immunohistochemistry confirmed the presence of PEDV reactivity and absence of TGEV reactivity in the enterocytes lining the ileum in ANPEP null pigs. The different receptor requirements for TGEV and PEDV have important implications in the development of new genetic tools for the control of enteric disease in pigs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11248-018-0100-3) contains supplementary material, which is available to authorized users.",2019 Oct 12,"['Whitworth, Kristin M.', 'Rowland, Raymond R. R.', 'Petrovan, Vlad', 'Sheahan, Maureen', 'Cino-Ozuna, Ada G.', 'Fang, Ying', 'Hesse, Richard', 'Mileham, Alan', 'Samuel, Melissa S.', 'Wells, Kevin D.', 'Prather, Randall S.']",Transgenic Res,,,True
20064252dde338a159a4af1c1ae9582d94240587,PMC,Association between viral seasonality and meteorological factors,http://dx.doi.org/10.1038/s41598-018-37481-y,PMC6353886,30700747,CC BY,"Numerous viruses can cause upper respiratory tract infections. They often precede serious lower respiratory tract infections. Each virus has a seasonal pattern, with peaks in activity in different seasons. We examined the effects of daily local meteorological data (temperature, relative humidity, “humidity-range” and dew point) from Edinburgh, Scotland on the seasonal variations in viral transmission. We identified the seasonality of rhinovirus, adenovirus, influenza A and B viruses, human parainfluenza viruses 1–3 (HPIV), respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) from the 52060 respiratory samples tested between 2009 and 2015 and then confirmed the same by a generalised linear model. We also investigated the relationship between meteorological factors and viral seasonality. Non-enveloped viruses were present throughout the year. Following logistic regression adenovirus, influenza viruses A, B, RSV and HMPV preferred low temperatures; RSV and influenza A virus preferred a narrow “humidity-range” and HPIV type 3 preferred the season with lower humidity. A change (i.e. increase or decrease) in specific meteorological factors is associated with an increase in activity of specific viruses at certain times of the year.",2019 Jan 30,"['Price, Rory Henry Macgregor', 'Graham, Catriona', 'Ramalingam, Sandeep']",Sci Rep,,,False
ca091dd5921084c9469553962a04f7a475893623,PMC,Association between viral seasonality and meteorological factors,http://dx.doi.org/10.1038/s41598-018-37481-y,PMC6353886,30700747,CC BY,"Numerous viruses can cause upper respiratory tract infections. They often precede serious lower respiratory tract infections. Each virus has a seasonal pattern, with peaks in activity in different seasons. We examined the effects of daily local meteorological data (temperature, relative humidity, “humidity-range” and dew point) from Edinburgh, Scotland on the seasonal variations in viral transmission. We identified the seasonality of rhinovirus, adenovirus, influenza A and B viruses, human parainfluenza viruses 1–3 (HPIV), respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) from the 52060 respiratory samples tested between 2009 and 2015 and then confirmed the same by a generalised linear model. We also investigated the relationship between meteorological factors and viral seasonality. Non-enveloped viruses were present throughout the year. Following logistic regression adenovirus, influenza viruses A, B, RSV and HMPV preferred low temperatures; RSV and influenza A virus preferred a narrow “humidity-range” and HPIV type 3 preferred the season with lower humidity. A change (i.e. increase or decrease) in specific meteorological factors is associated with an increase in activity of specific viruses at certain times of the year.",2019 Jan 30,"['Price, Rory Henry Macgregor', 'Graham, Catriona', 'Ramalingam, Sandeep']",Sci Rep,,,True
837abf94f591d8288f0b9faa53055d2724ff783f,PMC,CSF1R antagonism limits local restimulation of antiviral CD8(+) T cells during viral encephalitis,http://dx.doi.org/10.1186/s12974-019-1397-4,PMC6354430,30704498,CC BY,"BACKGROUND: Microglia are resident macrophages of the central nervous system (CNS) locally maintained through colony-stimulating factor 1 receptor (CSF1R) signaling. Microglial depletion via CSF1R inactivation improves cognition in mouse models of neuroinflammation, but limits virologic control in the CNS of mouse models of neurotropic infections by unknown mechanisms. We hypothesize that CSF1R plays a critical role in myeloid cell responses that restrict viral replication and locally restimulate recruited antiviral T cells within the CNS. METHODS: The impact of CSF1R signaling during West Nile virus infection was assessed in vivo using a mouse model of neurotropic infection. Pharmacological inactivation of CSF1R was achieved using PLX5622 prior to infection with virulent or attenuated strains of West Nile virus (WNV), an emerging neuropathogen. The subsequent effect of CSF1R antagonism on virologic control was assessed by measuring mortality and viral titers in the CNS and peripheral organs. Immune responses were assessed by flow cytometric-based phenotypic analyses of both peripheral and CNS immune cells. RESULTS: Mice treated with CSF1R antagonist prior to infection exhibited higher susceptibility to lethal WNV infection and lack of virologic control in both the CNS and periphery. CSFR1 antagonism reduced B7 co-stimulatory signals on peripheral and CNS antigen-presenting cells (APCs) by depleting CNS cellular sources, which limited local reactivation of CNS-infiltrating virus-specific T cells and reduced viral clearance. CONCLUSIONS: Our results demonstrate the impact of CSF1R antagonism on APC activation in the CNS and periphery and the importance of microglia in orchestrating the CNS immune response following neurotropic viral infection. These data will be an important consideration when assessing the benefit of CSF1R antagonism, which has been investigated as a therapeutic for neurodegenerative conditions, in which neuroinflammation is a contributing factor. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-019-1397-4) contains supplementary material, which is available to authorized users.",2019 Jan 31,"['Funk, Kristen E.', 'Klein, Robyn S.']",J Neuroinflammation,,,True
63a206dc7356041e3054110691cbd8146278cee1,PMC,"Quality and quantity of dromedary camel DNA sampled from whole-blood, saliva, and tail-hair",http://dx.doi.org/10.1371/journal.pone.0211743,PMC6355012,30703133,CC BY,"Camels are livestock with unique adaptations to hot-arid regions. To effectively study camel traits, a biobank of camel DNA specimens with associated biological information is needed. We examined whole-blood, saliva (buccal swabs), and tail-hair follicle samples to determine which is the best source for establishing a DNA biobank. We inspected five amounts of each of whole-blood, buccal swabs, and tail-hair follicles in nine camels, both qualitatively via gel electrophoresis and quantitatively using a NanoDrop spectrophotometer. We also tested the effects of long term-storage on the quality and quantity of DNA, and measured the rate of degradation, by analyzing three buccal swab samples and 30 tail-hair follicles over a period of nine months. Good quality DNA, in the form of visible large size DNA bands, was extracted from all three sources, for all five amounts. The five volumes of whole-blood samples (20–100μl) provided ~0.4–3.6 μg, the five quantities of buccal swabs (1–5) produced ~0.1–12 μg, while the five amounts of tail-hair follicles (10–50) resulted in ~0.7–25 μg. No differences in the rate of degradation of buccal swab and tail-hair follicle DNA were detected, but there was clearly greater deterioration in the quality of DNA extracted from buccal swabs when compared to tail-hair follicles. We recommend using tail-hair samples for camel DNA biobanking, because it resulted in both an adequate quality and quantity of DNA, along with its ease of collection, transportation, and storage. Compared to its success in studies of other domesticated animals, we anticipate that using ~50 tail-hair follicles will provide sufficient DNA for sequencing or SNP genotyping.",2019 Jan 31,"['Alhaddad, Hasan', 'Maraqa, Tasneem', 'Alabdulghafour, Suha', 'Alaskar, Huda', 'Alaqeely, Randa', 'Almathen, Faisal', 'Alhajeri, Bader H.']",PLoS One,,,True
5f9965c72bcb135959c16ed18601bc4485318a88,PMC,"A pilot, open labelled, randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold",http://dx.doi.org/10.1038/s41598-018-37703-3,PMC6355924,30705369,CC BY,"There are no antivirals to treat viral upper respiratory tract infection (URTI). Since numerous viruses cause URTI, antiviral therapy is impractical. As we have evidence of chloride-ion dependent innate antiviral response in epithelial cells, we conducted a pilot, non-blinded, randomised controlled trial of hypertonic saline nasal irrigation and gargling (HSNIG) vs standard care on healthy adults within 48 hours of URTI onset to assess recruitment (primary outcome). Acceptability, symptom duration and viral shedding were secondary outcomes. Participants maintained a symptom diary until well for two days or a maximum of 14 days and collected 5 sequential mid-turbinate swabs to measure viral shedding. The intervention arm prepared hypertonic saline and performed HSNIG. We recruited 68 participants (2.6 participants/week; November 2014-March 2015). A participant declined after randomisation. Another was on antibiotics and hence removed (Intervention:32, Control:34). Follow up data was available from 61 (Intervention:30, Control:31). 87% found HSNIG acceptable, 93% thought HSNIG made a difference to their symptoms. In the intervention arm, duration of illness was lower by 1.9 days (p = 0.01), over-the-counter medications (OTCM) use by 36% (p = 0.004), transmission within household contacts by 35% (p = 0.006) and viral shedding by ≥0.5 log(10)/day (p = 0.04). We hence need a larger trial to confirm our findings.",2019 Jan 31,"['Ramalingam, Sandeep', 'Graham, Catriona', 'Dove, Jenny', 'Morrice, Lynn', 'Sheikh, Aziz']",Sci Rep,,,False
15909c5986b0407310ef629ce19ebe562be7c20c,PMC,"A pilot, open labelled, randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold",http://dx.doi.org/10.1038/s41598-018-37703-3,PMC6355924,30705369,CC BY,"There are no antivirals to treat viral upper respiratory tract infection (URTI). Since numerous viruses cause URTI, antiviral therapy is impractical. As we have evidence of chloride-ion dependent innate antiviral response in epithelial cells, we conducted a pilot, non-blinded, randomised controlled trial of hypertonic saline nasal irrigation and gargling (HSNIG) vs standard care on healthy adults within 48 hours of URTI onset to assess recruitment (primary outcome). Acceptability, symptom duration and viral shedding were secondary outcomes. Participants maintained a symptom diary until well for two days or a maximum of 14 days and collected 5 sequential mid-turbinate swabs to measure viral shedding. The intervention arm prepared hypertonic saline and performed HSNIG. We recruited 68 participants (2.6 participants/week; November 2014-March 2015). A participant declined after randomisation. Another was on antibiotics and hence removed (Intervention:32, Control:34). Follow up data was available from 61 (Intervention:30, Control:31). 87% found HSNIG acceptable, 93% thought HSNIG made a difference to their symptoms. In the intervention arm, duration of illness was lower by 1.9 days (p = 0.01), over-the-counter medications (OTCM) use by 36% (p = 0.004), transmission within household contacts by 35% (p = 0.006) and viral shedding by ≥0.5 log(10)/day (p = 0.04). We hence need a larger trial to confirm our findings.",2019 Jan 31,"['Ramalingam, Sandeep', 'Graham, Catriona', 'Dove, Jenny', 'Morrice, Lynn', 'Sheikh, Aziz']",Sci Rep,,,True
4facb7cbe620956211550e1a035b0281f2db5cfc,PMC,Epidemic intelligence needs of stakeholders in the Asia–Pacific region,http://dx.doi.org/10.5365/wpsar.2018.9.2.009,PMC6356040,30766745,CC BY,"OBJECTIVE: To understand the global outbreak surveillance needs of stakeholders involved in epidemic response in selected countries and areas in the Asia–Pacific region to inform development of an epidemic observatory, Epi-watch. METHODS: We designed an online, semi-structured stakeholder questionnaire to collect information on global outbreak surveillance sources and limitations from participants who use epidemic intelligence and outbreak alert services in their work in government and nongovernment organizations in the Asia–Pacific region. RESULTS: All respondents agreed that it was important to remain up to date with global outbreaks. The main reason cited for following global outbreak news was as an early warning for serious epidemics. Mainstream media and specialist Internet sources such as the World Health Organization (n = 54/91; 59%), the Program for Monitoring Emerging Diseases (ProMED)-mail (n = 45/91; 49%) and the United States Centers for Disease Control and Prevention (n = 31/91; 34%) were the most common sources for global outbreak news; rapid intelligence services such as HealthMap were less common (n = 9/91; 10%). Only 51% (n = 46/91) of respondents thought that their sources of outbreak news were timely and sufficient for their needs. CONCLUSION: For those who work in epidemic response, epidemic intelligence is important and widely used. Stakeholders are less aware of and less frequently use rapid sources such as HealthMap and rely more on validated but less timely traditional sources of disease surveillance. Users identified a need for more timely and reliable epidemic intelligence.",2018 Dec 18,"['Hii, Aurysia', 'Chughtai, Abrar Ahmad', 'Housen, Tambri', 'Saketa, Salanieta', 'Kunasekaran, Mohana Priya', 'Sulaiman, Feroza', 'Yanti, NK Semara', 'MacIntyre, Chandini Raina']",Western Pac Surveill Response J,,,True
2c0c9617097af6391e34b3f30dde6c1e6845d722,PMC,Modeling Arboviral Infection in Mice Lacking the Interferon Alpha/Beta Receptor,http://dx.doi.org/10.3390/v11010035,PMC6356211,30625992,CC BY,"Arboviruses are arthropod-borne viruses that exhibit worldwide distribution and are a constant threat, not only for public health but also for wildlife, domestic animals, and even plants. To study disease pathogenesis and to develop efficient and safe therapies, the use of an appropriate animal model is a critical concern. Adult mice with gene knockouts of the interferon α/β (IFN-α/β) receptor (IFNAR(−/−)) have been described as a model of arbovirus infections. Studies with the natural hosts of these viruses are limited by financial and ethical issues, and in some cases, the need to have facilities with a biosafety level 3 with sufficient space to accommodate large animals. Moreover, the number of animals in the experiments must provide results with statistical significance. Recent advances in animal models in the last decade among other gaps in knowledge have contributed to the better understanding of arbovirus infections. A tremendous advantage of the IFNAR(−/−) mouse model is the availability of a wide variety of reagents that can be used to study many aspects of the immune response to the virus. Although extrapolation of findings in mice to natural hosts must be done with care due to differences in the biology between mouse and humans, experimental infections of IFNAR(−/−) mice with several studied arboviruses closely mimics hallmarks of these viruses in their natural host. Therefore, IFNAR(−/−) mice are a good model to facilitate studies on arbovirus transmission, pathogenesis, virulence, and the protective efficacy of new vaccines. In this review article, the most important arboviruses that have been studied using the IFNAR(−/−) mouse model will be reviewed.",2019 Jan 8,"['Marín-Lopez, Alejandro', 'Calvo-Pinilla, Eva', 'Moreno, Sandra', 'Utrilla-Trigo, Sergio', 'Nogales, Aitor', 'Brun, Alejandro', 'Fikrig, Erol', 'Ortego, Javier']",Viruses,,,True
cd4c984e7afa08f850f9173578fbae31d92a64a5,PMC,Genetic Diversity and Phylodynamics of Avian Coronaviruses in Egyptian Wild Birds,http://dx.doi.org/10.3390/v11010057,PMC6356246,30646528,CC BY,"Avian coronaviruses (ACoVs) are continuously evolving and causing serious economic consequences in the poultry industry and around the globe. Owing to their extensive genetic diversity and high mutation rates, controlling ACoVs has become a challenge. In this context, the potential contribution of wild birds in the disease dynamics, especially in domesticated birds, remains largely unknown. In the present study, five hundred fifty-seven (n = 557) cloacal/fecal swabs were collected from four different wild bird species from eight Egyptian governorates during 2016 and a total of fourteen positive isolates were used for phylodynamics and evolutionary analysis. Genetic relatedness based on spike (S1) gene demonstrated the clustering of majority of these isolates where nine isolates grouped within Egy/variant 2 (IS/885 genotype) and five isolates clustered within Egy/variant 1 (IS/1494/06 genotype). Interestingly, these isolates showed noticeable genetic diversity and were clustered distal to the previously characterized Egy/variant 1 and Egy/variant 2 in Egyptian commercial poultry. The S1 gene based comparison of nucleotide identity percentages revealed that all fourteen isolates reported in this study were genetically related to the variant GI-23 lineage with 92–100% identity. Taken together, our results demonstrate that ACoVs are circulating in Egyptian wild birds and highlight their possible contributions in the disease dynamics. The study also proposes that regular monitoring of the ACoVs in wild birds is required to effectively assess the role of wild birds in disease spread, and the emergence of ACoVs strains in the country.",2019 Jan 14,"['A. Rohaim, Mohammed', 'F. El Naggar, Rania', 'M. Helal, Ahmed', 'M. Bayoumi, Mahmoud', 'A. El-Saied, Mohamed', 'A. Ahmed, Kawkab', 'Z. Shabbir, Muhammad', 'Munir, Muhammad']",Viruses,,,True
dcc46888d647f293c6f9d136aaf7d3a708558372,PMC,Middle East Respiratory Syndrome Vaccine Candidates: Cautious Optimism,http://dx.doi.org/10.3390/v11010074,PMC6356267,30658390,CC BY,"Efforts towards developing a vaccine for Middle East respiratory syndrome coronavirus (MERS-CoV) have yielded promising results. Utilizing a variety of platforms, several vaccine approaches have shown efficacy in animal models and begun to enter clinical trials. In this review, we summarize the current progress towards a MERS-CoV vaccine and highlight potential roadblocks identified from previous attempts to generate coronavirus vaccines.",2019 Jan 17,"['Schindewolf, Craig', 'Menachery, Vineet D.']",Viruses,,,True
69718b1722e6fb921fa5c56b5135454ddbdf7457,PMC,KDELR2 Competes with Measles Virus Envelope Proteins for Cellular Chaperones Reducing Their Chaperone-Mediated Cell Surface Transport,http://dx.doi.org/10.3390/v11010027,PMC6356275,30621148,CC BY,"Recently, we found that the cytidine deaminase APOBEC3G (A3G) inhibits measles (MV) replication. Using a microarray, we identified differential regulation of several host genes upon ectopic expression of A3G. One of the up-regulated genes, the endoplasmic reticulum (ER) protein retention receptor KDELR2, reduced MV replication ~5 fold when it was over-expressed individually in Vero and CEM-SS T cells. Silencing of KDELR2 in A3G-expressing Vero cells abrogated the antiviral activity induced by A3G, confirming its role as an A3G-regulated antiviral host factor. Recognition of the KDEL (Lys-Asp-Glu-Leu) motif by KDEL receptors initiates the retrograde transport of soluble proteins that have escaped the ER and play an important role in ER quality control. Although KDELR2 over-expression reduced MV titers in cell cultures, we observed no interaction between KDELR2 and the MV hemagglutinin (H) protein. Instead, KDELR2 retained chaperones in the ER, which are required for the correct folding and transport of the MV envelope glycoproteins H and fusion protein (F) to the cell surface. Our data indicate that KDELR2 competes with MV envelope proteins for binding to calnexin and GRP78/Bip, and that this interaction limits the availability of the chaperones for MV proteins, causing the reduction of virus spread and titers.",2019 Jan 4,"['Tiwarekar, Vishakha', 'Fehrholz, Markus', 'Schneider-Schaulies, Jürgen']",Viruses,,,True
697cf5b78c388d6e79a7a87ac9b82e4911de135a,PMC,Development of a Whole-Virus ELISA for Serological Evaluation of Domestic Livestock as Possible Hosts of Human Coronavirus NL63,http://dx.doi.org/10.3390/v11010043,PMC6356407,30634419,CC BY,"Known human coronaviruses are believed to have originated in animals and made use of intermediate hosts for transmission to humans. The intermediate hosts of most of the human coronaviruses are known, but not for HCoV-NL63. This study aims to assess the possible role of some major domestic livestock species as intermediate hosts of HCoV-NL63. We developed a testing algorithm for high throughput screening of livestock sera with ELISA and confirmation with recombinant immunofluorescence assay testing for antibodies against HCoV-NL63 in livestock. Optimization of the ELISA showed a capability of the assay to significantly distinguish HCoV-NL63 from HCoV-229E (U = 27.50, p < 0.001) and HCoV-OC43 (U = 55.50, p < 0.001) in coronavirus-characterized sera. Evaluation of the assay with collected human samples showed no significant difference in mean optical density values of immunofluorescence-classified HCoV-NL63-positive and HCoV-NL63-negative samples (F (1, 215) = 0.437, p = 0.509). All the top 5% (n = 8) most reactive human samples tested by ELISA were HCoV-NL63 positive by immunofluorescence testing. In comparison, only a proportion (84%, n = 42) of the top 25% were positive by immunofluorescence testing, indicating an increased probability of the highly ELISA reactive samples testing positive by the immunofluorescence assay. None of the top 5% most ELISA reactive livestock samples were positive for HCoV-NL63-related viruses by immunofluorescence confirmation. Ghanaian domestic livestock are not likely intermediate hosts of HCoV-NL63-related coronaviruses.",2019 Jan 9,"['El-Duah, Philip', 'Meyer, Benjamin', 'Sylverken, Augustina', 'Owusu, Michael', 'Gottula, Lina Theresa', 'Yeboah, Richmond', 'Lamptey, Jones', 'Frimpong, Yaw Oppong', 'Burimuah, Vitus', 'Folitse, Raphael', 'Agbenyega, Olivia', 'Oppong, Samuel', 'Adu-Sarkodie, Yaw', 'Drosten, Christian']",Viruses,,,True
19babdefd145a5becbc2a0b189eabdafa697de75,PMC,Bats and Coronaviruses,http://dx.doi.org/10.3390/v11010041,PMC6356540,30634396,CC BY,"Bats are speculated to be reservoirs of several emerging viruses including coronaviruses (CoVs) that cause serious disease in humans and agricultural animals. These include CoVs that cause severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), porcine epidemic diarrhea (PED) and severe acute diarrhea syndrome (SADS). Bats that are naturally infected or experimentally infected do not demonstrate clinical signs of disease. These observations have allowed researchers to speculate that bats are the likely reservoirs or ancestral hosts for several CoVs. In this review, we follow the CoV outbreaks that are speculated to have originated in bats. We review studies that have allowed researchers to identify unique adaptation in bats that may allow them to harbor CoVs without severe disease. We speculate about future studies that are critical to identify how bats can harbor multiple strains of CoVs and factors that enable these viruses to “jump” from bats to other mammals. We hope that this review will enable readers to identify gaps in knowledge that currently exist and initiate a dialogue amongst bat researchers to share resources to overcome present limitations.",2019 Jan 9,"['Banerjee, Arinjay', 'Kulcsar, Kirsten', 'Misra, Vikram', 'Frieman, Matthew', 'Mossman, Karen']",Viruses,,,True
0d1d6d059b8f14bab7c89cdcda4cda11e38233dc,PMC,Natural Products Isolated from Oriental Medicinal Herbs Inactivate Zika Virus,http://dx.doi.org/10.3390/v11010049,PMC6356660,30641880,CC BY,"Zika virus (ZIKV) has been associated with serious health conditions, and an intense search to discover different ways to prevent and treat ZIKV infection is underway. Berberine and emodin possess several pharmacological properties and have been shown to be particularly effective against the entry and replication of several viruses. We show that emodin and berberine trigger a virucidal effect on ZIKV. When the virus was exposed to 160 µM of berberine, a reduction of 77.6% in the infectivity was observed; when emodin was used (40 µM), this reduction was approximately 83.3%. Dynamic light scattering data showed that both compounds significantly reduce the hydrodynamic radius of virus particle in solution. We report here that berberine and emodin, two natural compounds, have strong virucidal effect in Zika virus.",2019 Jan 11,"['Batista, Mariana N.', 'Braga, Ana Cláudia S.', 'Campos, Guilherme Rodrigues Fernandes', 'Souza, Marcos Michel', 'de Matos, Renata Prandini Adum', 'Lopes, Tairine Zara', 'Candido, Natalia Maria', 'Lima, Maria Leticia Duarte', 'Machado, Francielly Cristina', 'de Andrade, Stephane Tereza Queiroz', 'Bittar, Cíntia', 'Nogueira, Maurício L.', 'Carneiro, Bruno M.', 'Mariutti, Ricardo B.', 'Arni, Raghuvir Krishnaswamy', 'Calmon, Marilia Freitas', 'Rahal, Paula']",Viruses,,,True
e6da0f2a56c73676ed6b6811cd8bca79b4dd2d57,PMC,Natural Products Isolated from Oriental Medicinal Herbs Inactivate Zika Virus,http://dx.doi.org/10.3390/v11010049,PMC6356660,30641880,CC BY,"Zika virus (ZIKV) has been associated with serious health conditions, and an intense search to discover different ways to prevent and treat ZIKV infection is underway. Berberine and emodin possess several pharmacological properties and have been shown to be particularly effective against the entry and replication of several viruses. We show that emodin and berberine trigger a virucidal effect on ZIKV. When the virus was exposed to 160 µM of berberine, a reduction of 77.6% in the infectivity was observed; when emodin was used (40 µM), this reduction was approximately 83.3%. Dynamic light scattering data showed that both compounds significantly reduce the hydrodynamic radius of virus particle in solution. We report here that berberine and emodin, two natural compounds, have strong virucidal effect in Zika virus.",2019 Jan 11,"['Batista, Mariana N.', 'Braga, Ana Cláudia S.', 'Campos, Guilherme Rodrigues Fernandes', 'Souza, Marcos Michel', 'de Matos, Renata Prandini Adum', 'Lopes, Tairine Zara', 'Candido, Natalia Maria', 'Lima, Maria Leticia Duarte', 'Machado, Francielly Cristina', 'de Andrade, Stephane Tereza Queiroz', 'Bittar, Cíntia', 'Nogueira, Maurício L.', 'Carneiro, Bruno M.', 'Mariutti, Ricardo B.', 'Arni, Raghuvir Krishnaswamy', 'Calmon, Marilia Freitas', 'Rahal, Paula']",Viruses,,,False
bfda858fc7207fb61f7e5b5af659971740e1b6c5,PMC,The 18th Rocky Mountain Virology Association Meeting,http://dx.doi.org/10.3390/v11010004,PMC6356675,30577629,CC BY,"This autumn, approximately 100 scientists and students from the Rocky Mountain area along with invited speakers attended the 18th annual meeting of the Rocky Mountain Virology Association that was held at the Colorado State University Mountain Campus. The two-day gathering featured 31 talks and 33 posters all of which focused on specific areas of current virology and prion protein research. Since the keynote presentation focused on the oligoadenylate synthetase-ribonuclease L pathway the main area of focus was on host–virus interactions, however other areas of interest included virus vectors, current models of virus infections, prevention and treatment of virus infections, separate sessions on RNA viruses and prion proteins, and a special talk highlighting various attributes of targeted next-generation sequencing. The meeting was held at the peak of the fall Aspen colors surrounded by five mountains >11000 ft (3.3 km) where the secluded campus provided the ideal setting for extended discussions and outdoor exercise. On behalf of the Rocky Mountain Virology Association, this report summarizes 42 selected presentations.",2018 Dec 21,"['Rovnak, Joel', 'Clair, Laura A. St.', 'Krieger, Kirsten', 'Lian, Elena', 'Perera, Rushika', 'Cohrs, Randall J.']",Viruses,,,False
cffa9b1def2d5c6d7bae6fb1ea9fa07948885c05,PMC,Combining a Fusion Inhibitory Peptide Targeting the MERS-CoV S2 Protein HR1 Domain and a Neutralizing Antibody Specific for the S1 Protein Receptor-Binding Domain (RBD) Showed Potent Synergism against Pseudotyped MERS-CoV with or without Mutations in RBD,http://dx.doi.org/10.3390/v11010031,PMC6356712,30621343,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) has continuously posed a threat to public health worldwide, yet no therapeutics or vaccines are currently available to prevent or treat MERS-CoV infection. We previously identified a fusion inhibitory peptide (HR2P-M2) targeting the MERS-CoV S2 protein HR1 domain and a highly potent neutralizing monoclonal antibody (m336) specific to the S1 spike protein receptor-binding domain (RBD). However, m336 was found to have reduced efficacy against MERS-CoV strains with mutations in RBD, and HR2P-M2 showed low potency, thus limiting the clinical application of each when administered separately. However, we herein report that the combination of m336 and HR2P-M2 exhibited potent synergism in inhibiting MERS-CoV S protein-mediated cell–cell fusion and infection by MERS-CoV pseudoviruses with or without mutations in the RBD, resulting in the enhancement of antiviral activity in contrast to either one administered alone. Thus, this combinatorial strategy could be used in clinics for the urgent treatment of MERS-CoV-infected patients.",2019 Jan 6,"['Wang, Cong', 'Hua, Chen', 'Xia, Shuai', 'Li, Weihua', 'Lu, Lu', 'Jiang, Shibo']",Viruses,,,True
5067fdcb872ccb895d1d4e5a856ad81aabe9b7b9,PMC,Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV,http://dx.doi.org/10.3390/v11010039,PMC6356766,30634407,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1β levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1β fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. These results will further our understanding of the pathogenesis of MERS-CoV infection.",2019 Jan 9,"['Jiang, Yuting', 'Li, Junfeng', 'Teng, Yue', 'Sun, Hong', 'Tian, Guang', 'He, Lei', 'Li, Pei', 'Chen, Yuehong', 'Guo, Yan', 'Li, Jiangfan', 'Zhao, Guangyu', 'Zhou, Yusen', 'Sun, Shihui']",Viruses,,,True
ad552caeace5008fba0e156d30a5e6f8f6c2f420,PMC,Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms,http://dx.doi.org/10.3390/toxins11010032,PMC6356842,30634620,CC BY,"The recombinant antibody fragments generated against the toxic components of scorpion venoms are considered a promising alternative for obtaining new antivenoms for therapy. Using directed evolution and site-directed mutagenesis, it was possible to generate a human single-chain antibody fragment with a broad cross-reactivity that retained recognition for its original antigen. This variant is the first antibody fragment that neutralizes the effect of an estimated 13 neurotoxins present in the venom of nine species of Mexican scorpions. This single antibody fragment showed the properties of a polyvalent antivenom. These results represent a significant advance in the development of new antivenoms against scorpion stings, since the number of components would be minimized due to their broad cross-neutralization capacity, while at the same time bypassing animal immunization.",2019 Jan 10,"['Riaño-Umbarila, Lidia', 'Gómez-Ramírez, Ilse V.', 'Ledezma-Candanoza, Luis M.', 'Olamendi-Portugal, Timoteo', 'Rodríguez-Rodríguez, Everardo Remi', 'Fernández-Taboada, Guillermo', 'Possani, Lourival D.', 'Becerril, Baltazar']",Toxins (Basel),,,True
0ea2b0aff1eba0e7d91e957adb1321869cc720a4,PMC,Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms,http://dx.doi.org/10.3390/toxins11010032,PMC6356842,30634620,CC BY,"The recombinant antibody fragments generated against the toxic components of scorpion venoms are considered a promising alternative for obtaining new antivenoms for therapy. Using directed evolution and site-directed mutagenesis, it was possible to generate a human single-chain antibody fragment with a broad cross-reactivity that retained recognition for its original antigen. This variant is the first antibody fragment that neutralizes the effect of an estimated 13 neurotoxins present in the venom of nine species of Mexican scorpions. This single antibody fragment showed the properties of a polyvalent antivenom. These results represent a significant advance in the development of new antivenoms against scorpion stings, since the number of components would be minimized due to their broad cross-neutralization capacity, while at the same time bypassing animal immunization.",2019 Jan 10,"['Riaño-Umbarila, Lidia', 'Gómez-Ramírez, Ilse V.', 'Ledezma-Candanoza, Luis M.', 'Olamendi-Portugal, Timoteo', 'Rodríguez-Rodríguez, Everardo Remi', 'Fernández-Taboada, Guillermo', 'Possani, Lourival D.', 'Becerril, Baltazar']",Toxins (Basel),,,False
dfdeaf42e832860f70d1583ef54f9b319b5dd2a9,PMC,Single Chain Fragment Variable (scFv) Antibodies Targeting the Spike Protein of Porcine Epidemic Diarrhea Virus Provide Protection against Viral Infection in Piglets,http://dx.doi.org/10.3390/v11010058,PMC6356844,30646521,CC BY,"Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe diarrhea and death in neonatal piglets. Passive immunization with neutralizing antibodies against PEDV is an effective prevention measure. In this study, single chain fragment variable (scFv) antibodies against PEDV were screened from the porcine scFv phage display library. After four rounds of biopanning, scFvs that showed higher affinity to the PEDV antigen were selected for further study. The scFv genes were cloned into the expression plasmid for recombinant protein expression. These scFvs were shown to inhibit PEDV infectivity by the plaque reduction neutralization assay. Immunofluorescence assay (IFA) revealed that the epitopes recognized by these scFvs were in the S1 region of the spike protein. The potential of scFvs to provide prevention against PEDV infections in piglets was further investigated. Piglets orally administered scFvs showed no to mild clinical symptoms, significantly less viral shedding, no mortality and no intestinal lesions. The field application also revealed that the survival rate of piglets was significantly increased by oral administration of scFvs. Our data support the potential role of scFvs in the prevention and treatment of PEDV infection.",2019 Jan 14,"['Zhang, Fanqing', 'Chen, Yuxue', 'Ke, Yong', 'Zhang, Lei', 'Zhang, Bo', 'Yang, Liang', 'Zhu, Jianguo']",Viruses,,,True
7fa8e7b51add58ce83dcef272e6f2e09d05670bd,PMC,Single Chain Fragment Variable (scFv) Antibodies Targeting the Spike Protein of Porcine Epidemic Diarrhea Virus Provide Protection against Viral Infection in Piglets,http://dx.doi.org/10.3390/v11010058,PMC6356844,30646521,CC BY,"Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe diarrhea and death in neonatal piglets. Passive immunization with neutralizing antibodies against PEDV is an effective prevention measure. In this study, single chain fragment variable (scFv) antibodies against PEDV were screened from the porcine scFv phage display library. After four rounds of biopanning, scFvs that showed higher affinity to the PEDV antigen were selected for further study. The scFv genes were cloned into the expression plasmid for recombinant protein expression. These scFvs were shown to inhibit PEDV infectivity by the plaque reduction neutralization assay. Immunofluorescence assay (IFA) revealed that the epitopes recognized by these scFvs were in the S1 region of the spike protein. The potential of scFvs to provide prevention against PEDV infections in piglets was further investigated. Piglets orally administered scFvs showed no to mild clinical symptoms, significantly less viral shedding, no mortality and no intestinal lesions. The field application also revealed that the survival rate of piglets was significantly increased by oral administration of scFvs. Our data support the potential role of scFvs in the prevention and treatment of PEDV infection.",2019 Jan 14,"['Zhang, Fanqing', 'Chen, Yuxue', 'Ke, Yong', 'Zhang, Lei', 'Zhang, Bo', 'Yang, Liang', 'Zhu, Jianguo']",Viruses,,,False
e38a8320180661475487156ee68de426868e6c45,PMC,"Endolysosomal Ca(2+) Signalling and Cancer Hallmarks: Two-Pore Channels on the Move, TRPML1 Lags Behind!",http://dx.doi.org/10.3390/cancers11010027,PMC6356888,30591696,CC BY,"The acidic vesicles of the endolysosomal (EL) system are emerging as an intracellular Ca(2+) store implicated in the regulation of multiple cellular functions. The EL Ca(2+) store releases Ca(2+) through a variety of Ca(2+)-permeable channels, including Transient Receptor Potential (TRP) Mucolipin 1-3 (TRPML1-3) and two-pore channels 1-2 (TPC1-2), whereas EL Ca(2+) refilling is sustained by the proton gradient across the EL membrane and/or by the endoplasmic reticulum (ER). EL Ca(2+) signals may be either spatially restricted to control vesicle trafficking, autophagy and membrane repair or may be amplified into a global Ca(2+) signal through the Ca(2+)-dependent recruitment of ER-embedded channels. Emerging evidence suggested that nicotinic acid adenine dinucleotide phosphate (NAADP)-gated TPCs sustain multiple cancer hallmarks, such as migration, invasiveness and angiogenesis. Herein, we first survey the EL Ca(2+) refilling and release mechanisms and then focus on the oncogenic role of EL Ca(2+) signaling. While the evidence in favor of TRPML1 involvement in neoplastic transformation is yet to be clearly provided, TPCs are emerging as an alternative target for anticancer therapies.",2018 Dec 27,"['Faris, Pawan', 'Shekha, Mudhir', 'Montagna, Daniela', 'Guerra, Germano', 'Moccia, Francesco']",Cancers (Basel),,,True
b7f56c8f1b2b82f7eae3786d2e59963b2a9b6d85,PMC,Drivers of MERS-CoV Emergence in Qatar,http://dx.doi.org/10.3390/v11010022,PMC6356962,30602691,CC BY,"MERS-CoV (Middle East respiratory syndrome corona virus) antibodies were detected in camels since 1983, but the first human case was only detected in 2012. This study sought to identify and quantify possible drivers for the MERS-CoV emergence and spillover to humans. A list of potential human, animal and environmental drivers for disease emergence were identified from literature. Trends in possible drivers were analyzed from national and international databases, and through structured interviews with experts in Qatar. The discovery and exploitation of oil and gas led to a 5-fold increase in Qatar GDP coupled with a 7-fold population growth in the past 30 years. The lifestyle gradually transformed from Bedouin life to urban sedentary life, along with a sharp increase in obesity and other comorbidities. Owing to substantial governmental support, camel husbandry and competitions flourished, exacerbating the already rapidly occurring desertification that forced banning of free grazing in 2005. Consequently, camels were housed in compact barns alongside their workers. The transition in husbandry leading to high density camel farming along with increased exposure to humans, combined with the increase of camel movement for the racing and breeding industry, have led to a convergence of factors driving spillover of MERS-CoV from camels to humans.",2018 Dec 31,"['Farag, Elmoubasher', 'Sikkema, Reina S.', 'Vinks, Tinka', 'Islam, Md Mazharul', 'Nour, Mohamed', 'Al-Romaihi, Hamad', 'Al Thani, Mohammed', 'Atta, Muzzamil', 'Alhajri, Farhoud H.', 'Al-Marri, Salih', 'AlHajri, Mohd', 'Reusken, Chantal', 'Koopmans, Marion']",Viruses,,,True
f40bb0be60659e3a06368dc470521b39bdfa279c,PMC,Drivers of MERS-CoV Emergence in Qatar,http://dx.doi.org/10.3390/v11010022,PMC6356962,30602691,CC BY,"MERS-CoV (Middle East respiratory syndrome corona virus) antibodies were detected in camels since 1983, but the first human case was only detected in 2012. This study sought to identify and quantify possible drivers for the MERS-CoV emergence and spillover to humans. A list of potential human, animal and environmental drivers for disease emergence were identified from literature. Trends in possible drivers were analyzed from national and international databases, and through structured interviews with experts in Qatar. The discovery and exploitation of oil and gas led to a 5-fold increase in Qatar GDP coupled with a 7-fold population growth in the past 30 years. The lifestyle gradually transformed from Bedouin life to urban sedentary life, along with a sharp increase in obesity and other comorbidities. Owing to substantial governmental support, camel husbandry and competitions flourished, exacerbating the already rapidly occurring desertification that forced banning of free grazing in 2005. Consequently, camels were housed in compact barns alongside their workers. The transition in husbandry leading to high density camel farming along with increased exposure to humans, combined with the increase of camel movement for the racing and breeding industry, have led to a convergence of factors driving spillover of MERS-CoV from camels to humans.",2018 Dec 31,"['Farag, Elmoubasher', 'Sikkema, Reina S.', 'Vinks, Tinka', 'Islam, Md Mazharul', 'Nour, Mohamed', 'Al-Romaihi, Hamad', 'Al Thani, Mohammed', 'Atta, Muzzamil', 'Alhajri, Farhoud H.', 'Al-Marri, Salih', 'AlHajri, Mohd', 'Reusken, Chantal', 'Koopmans, Marion']",Viruses,,,False
9685fb039a5be9e5466be1ee3b0f38a5dd7cc217,PMC,CSV2018: The 2nd Symposium of the Canadian Society for Virology,http://dx.doi.org/10.3390/v11010079,PMC6356965,30669273,CC BY,"The 2nd Symposium of the Canadian Society for Virology (CSV2018) was held in June 2018 in Halifax, Nova Scotia, Canada, as a featured event marking the 200th anniversary of Dalhousie University. CSV2018 attracted 175 attendees from across Canada and around the world, more than double the number that attended the first CSV symposium two years earlier. CSV2018 provided a forum to discuss a wide range of topics in virology including human, veterinary, plant, and microbial pathogens. Invited keynote speakers included David Kelvin (Dalhousie University and Shantou University Medical College) who provided a historical perspective on influenza on the 100th anniversary of the 1918 pandemic; Sylvain Moineau (Université Laval) who described CRISPR-Cas systems and anti-CRISPR proteins in warfare between bacteriophages and their host microbes; and Kate O’Brien (then from Johns Hopkins University, now relocated to the World Health Organization where she is Director of Immunization, Vaccines and Biologicals), who discussed the underlying viral etiology for pneumonia in the developing world, and the evidence for respiratory syncytial virus (RSV) as a primary cause. Reflecting a strong commitment of Canadian virologists to science communication, CSV2018 featured the launch of Halifax’s first annual Soapbox Science event to enable public engagement with female scientists, and the live-taping of the 499th episode of the This Week in Virology (TWIV) podcast, hosted by Vincent Racaniello (Columbia University) and science writer Alan Dove. TWIV featured interviews of CSV co-founders Nathalie Grandvaux (Université de Montréal) and Craig McCormick (Dalhousie University), who discussed the origins and objectives of the new society; Ryan Noyce (University of Alberta), who discussed technical and ethical considerations of synthetic virology; and Kate O’Brien, who discussed vaccines and global health. Finally, because CSV seeks to provide a better future for the next generation of Canadian virologists, the symposium featured a large number of oral and poster presentations from trainees and closed with the awarding of presentation prizes to trainees, followed by a tour of the Halifax Citadel National Historic Site and an evening of entertainment at the historic Alexander Keith’s Brewery.",2019 Jan 18,"['Grandvaux, Nathalie', 'McCormick, Craig']",Viruses,,,True
3f23d2283c45fc77411d8b9cc748ddf8d1de15e8,PMC,Advances in MERS-CoV Vaccines and Therapeutics Based on the Receptor-Binding Domain,http://dx.doi.org/10.3390/v11010060,PMC6357101,30646569,CC BY,"Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is an infectious virus that was first reported in 2012. The MERS-CoV genome encodes four major structural proteins, among which the spike (S) protein has a key role in viral infection and pathogenesis. The receptor-binding domain (RBD) of the S protein contains a critical neutralizing domain and is an important target for development of MERS vaccines and therapeutics. In this review, we describe the relevant features of the MERS-CoV S-protein RBD, summarize recent advances in the development of MERS-CoV RBD-based vaccines and therapeutic antibodies, and illustrate potential challenges and strategies to further improve their efficacy.",2019 Jan 14,"['Zhou, Yusen', 'Yang, Yang', 'Huang, Jingwei', 'Jiang, Shibo', 'Du, Lanying']",Viruses,,,True
3d4b0d8d4ac0c8419efb82278b823952e94d1393,PMC,Host and Viral Proteins Modulating Ebola and Marburg Virus Egress,http://dx.doi.org/10.3390/v11010025,PMC6357148,30609802,CC BY,"The filoviruses Ebolavirus and Marburgvirus are among the deadliest viral pathogens known to infect humans, causing emerging diseases with fatality rates of up to 90% during some outbreaks. The replication cycles of these viruses are comprised of numerous complex molecular processes and interactions with their human host, with one key feature being the means by which nascent virions exit host cells to spread to new cells and ultimately to a new host. This review focuses on our current knowledge of filovirus egress and the viral and host factors and processes that are involved. Within the virus, these factors consist of the major matrix protein, viral protein 40 (VP40), which is necessary and sufficient for viral particle release, and nucleocapsid and glycoprotein that interact with VP40 to promote egress. In the host cell, some proteins are hijacked by filoviruses in order to enhance virion budding capacity that include members of the family of E3 ubiquitin ligase and the endosomal sorting complexes required for transport (ESCRT) pathway, while others such as tetherin inhibit viral egress. An understanding of these molecular interactions that modulate viral particle egress provides an important opportunity to identify new targets for the development of antivirals to prevent and treat filovirus infections.",2019 Jan 3,"['Gordon, Tamsin B.', 'Hayward, Joshua A.', 'Marsh, Glenn A.', 'Baker, Michelle L.', 'Tachedjian, Gilda']",Viruses,,,True
e68b0f3da8a02a8f0b86869e533eaf549f70ff9a,PMC,Potent MERS-CoV Fusion Inhibitory Peptides Identified from HR2 Domain in Spike Protein of Bat Coronavirus HKU4,http://dx.doi.org/10.3390/v11010056,PMC6357153,30646495,CC BY,"The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and caused continual outbreaks worldwide with high mortality. However, no effective anti-MERS-CoV drug is currently available. Recently, numerous evolutionary studies have suggested that MERS-CoV originated from bat coronavirus (BatCoV). We herein reported that three peptides derived from the HR2 region in spike protein of BatCoV HKU4, including HKU4-HR2P1, HKU4-HR2P2 and HKU4-HR2P3, could bind the MERS-CoV HR1-derived peptide to form a six-helix bundle (6-HB) with high stability. Moreover, these peptides, particularly HKU4-HR2P2 and HKU4-HR2P3, exhibited potent inhibitory activity against MERS-CoV S-mediated cell–cell fusion and viral infection, suggesting that these HKU4 HR2-derived peptides could be candidates for futher development as antiviral agents against MERS-CoV infection.",2019 Jan 14,"['Xia, Shuai', 'Lan, Qiaoshuai', 'Pu, Jing', 'Wang, Cong', 'Liu, Zezhong', 'Xu, Wei', 'Wang, Qian', 'Liu, Huan', 'Jiang, Shibo', 'Lu, Lu']",Viruses,,,True
af09d53e351e3ad51c95fd313336da0379ac85ff,PMC,Potent MERS-CoV Fusion Inhibitory Peptides Identified from HR2 Domain in Spike Protein of Bat Coronavirus HKU4,http://dx.doi.org/10.3390/v11010056,PMC6357153,30646495,CC BY,"The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and caused continual outbreaks worldwide with high mortality. However, no effective anti-MERS-CoV drug is currently available. Recently, numerous evolutionary studies have suggested that MERS-CoV originated from bat coronavirus (BatCoV). We herein reported that three peptides derived from the HR2 region in spike protein of BatCoV HKU4, including HKU4-HR2P1, HKU4-HR2P2 and HKU4-HR2P3, could bind the MERS-CoV HR1-derived peptide to form a six-helix bundle (6-HB) with high stability. Moreover, these peptides, particularly HKU4-HR2P2 and HKU4-HR2P3, exhibited potent inhibitory activity against MERS-CoV S-mediated cell–cell fusion and viral infection, suggesting that these HKU4 HR2-derived peptides could be candidates for futher development as antiviral agents against MERS-CoV infection.",2019 Jan 14,"['Xia, Shuai', 'Lan, Qiaoshuai', 'Pu, Jing', 'Wang, Cong', 'Liu, Zezhong', 'Xu, Wei', 'Wang, Qian', 'Liu, Huan', 'Jiang, Shibo', 'Lu, Lu']",Viruses,,,False
05192151667b1bb4e3405de11f6e4ae2f844e7c5,PMC,"From SARS to MERS, Thrusting Coronaviruses into the Spotlight",http://dx.doi.org/10.3390/v11010059,PMC6357155,30646565,CC BY,"Coronaviruses (CoVs) have formerly been regarded as relatively harmless respiratory pathogens to humans. However, two outbreaks of severe respiratory tract infection, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), as a result of zoonotic CoVs crossing the species barrier, caused high pathogenicity and mortality rates in human populations. This brought CoVs global attention and highlighted the importance of controlling infectious pathogens at international borders. In this review, we focus on our current understanding of the epidemiology, pathogenesis, prevention, and treatment of SARS-CoV and MERS-CoV, as well as provides details on the pivotal structure and function of the spike proteins (S proteins) on the surface of each of these viruses. For building up more suitable animal models, we compare the current animal models recapitulating pathogenesis and summarize the potential role of host receptors contributing to diverse host affinity in various species. We outline the research still needed to fully elucidate the pathogenic mechanism of these viruses, to construct reproducible animal models, and ultimately develop countermeasures to conquer not only SARS-CoV and MERS-CoV, but also these emerging coronaviral diseases.",2019 Jan 14,"['Song, Zhiqi', 'Xu, Yanfeng', 'Bao, Linlin', 'Zhang, Ling', 'Yu, Pin', 'Qu, Yajin', 'Zhu, Hua', 'Zhao, Wenjie', 'Han, Yunlin', 'Qin, Chuan']",Viruses,,,True
6aea0cd2aa64321c5528944e105c69a167350dbd,PMC,Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication,http://dx.doi.org/10.3390/v11010073,PMC6357182,30654597,CC BY,"Lipids play numerous indispensable cellular functions and are involved in multiple steps in the replication cycle of viruses. Infections by human-pathogenic coronaviruses result in diverse clinical outcomes, ranging from self-limiting flu-like symptoms to severe pneumonia with extrapulmonary manifestations. Understanding how cellular lipids may modulate the pathogenicity of human-pathogenic coronaviruses remains poor. To this end, we utilized the human coronavirus 229E (HCoV-229E) as a model coronavirus to comprehensively characterize the host cell lipid response upon coronavirus infection with an ultra-high performance liquid chromatography-mass spectrometry (UPLC–MS)-based lipidomics approach. Our results revealed that glycerophospholipids and fatty acids (FAs) were significantly elevated in the HCoV-229E-infected cells and the linoleic acid (LA) to arachidonic acid (AA) metabolism axis was markedly perturbed upon HCoV-229E infection. Interestingly, exogenous supplement of LA or AA in HCoV-229E-infected cells significantly suppressed HCoV-229E virus replication. Importantly, the inhibitory effect of LA and AA on virus replication was also conserved for the highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV). Taken together, our study demonstrated that host lipid metabolic remodeling was significantly associated with human-pathogenic coronavirus propagation. Our data further suggested that lipid metabolism regulation would be a common and druggable target for coronavirus infections.",2019 Jan 16,"['Yan, Bingpeng', 'Chu, Hin', 'Yang, Dong', 'Sze, Kong-Hung', 'Lai, Pok-Man', 'Yuan, Shuofeng', 'Shuai, Huiping', 'Wang, Yixin', 'Kao, Richard Yi-Tsun', 'Chan, Jasper Fuk-Woo', 'Yuen, Kwok-Yung']",Viruses,,,True
1189c2ec13fe469008397cf62de9cd6802cd4eb3,PMC,Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication,http://dx.doi.org/10.3390/v11010073,PMC6357182,30654597,CC BY,"Lipids play numerous indispensable cellular functions and are involved in multiple steps in the replication cycle of viruses. Infections by human-pathogenic coronaviruses result in diverse clinical outcomes, ranging from self-limiting flu-like symptoms to severe pneumonia with extrapulmonary manifestations. Understanding how cellular lipids may modulate the pathogenicity of human-pathogenic coronaviruses remains poor. To this end, we utilized the human coronavirus 229E (HCoV-229E) as a model coronavirus to comprehensively characterize the host cell lipid response upon coronavirus infection with an ultra-high performance liquid chromatography-mass spectrometry (UPLC–MS)-based lipidomics approach. Our results revealed that glycerophospholipids and fatty acids (FAs) were significantly elevated in the HCoV-229E-infected cells and the linoleic acid (LA) to arachidonic acid (AA) metabolism axis was markedly perturbed upon HCoV-229E infection. Interestingly, exogenous supplement of LA or AA in HCoV-229E-infected cells significantly suppressed HCoV-229E virus replication. Importantly, the inhibitory effect of LA and AA on virus replication was also conserved for the highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV). Taken together, our study demonstrated that host lipid metabolic remodeling was significantly associated with human-pathogenic coronavirus propagation. Our data further suggested that lipid metabolism regulation would be a common and druggable target for coronavirus infections.",2019 Jan 16,"['Yan, Bingpeng', 'Chu, Hin', 'Yang, Dong', 'Sze, Kong-Hung', 'Lai, Pok-Man', 'Yuan, Shuofeng', 'Shuai, Huiping', 'Wang, Yixin', 'Kao, Richard Yi-Tsun', 'Chan, Jasper Fuk-Woo', 'Yuen, Kwok-Yung']",Viruses,,,False
3af2a50a4711db48012cf6972cb579f85cf1da40,PMC,Recognition of aerosol transmission of infectious agents: a commentary,http://dx.doi.org/10.1186/s12879-019-3707-y,PMC6357359,30704406,CC BY,"Although short-range large-droplet transmission is possible for most respiratory infectious agents, deciding on whether the same agent is also airborne has a potentially huge impact on the types (and costs) of infection control interventions that are required. The concept and definition of aerosols is also discussed, as is the concept of large droplet transmission, and airborne transmission which is meant by most authors to be synonymous with aerosol transmission, although some use the term to mean either large droplet or aerosol transmission. However, these terms are often used confusingly when discussing specific infection control interventions for individual pathogens that are accepted to be mostly transmitted by the airborne (aerosol) route (e.g. tuberculosis, measles and chickenpox). It is therefore important to clarify such terminology, where a particular intervention, like the type of personal protective equipment (PPE) to be used, is deemed adequate to intervene for this potential mode of transmission, i.e. at an N95 rather than surgical mask level requirement. With this in mind, this review considers the commonly used term of ‘aerosol transmission’ in the context of some infectious agents that are well-recognized to be transmissible via the airborne route. It also discusses other agents, like influenza virus, where the potential for airborne transmission is much more dependent on various host, viral and environmental factors, and where its potential for aerosol transmission may be underestimated.",2019 Jan 31,"['Tellier, Raymond', 'Li, Yuguo', 'Cowling, Benjamin J.', 'Tang, Julian W.']",BMC Infect Dis,,,True
cf418ee0dbf748c0464bc42111a8fc79e00dab3c,PMC,Are China’s oldest-old living longer with less disability? A longitudinal modeling analysis of birth cohorts born 10 years apart,http://dx.doi.org/10.1186/s12916-019-1259-z,PMC6357399,30704529,CC BY,"BACKGROUND: China has transitioned from being one of the fastest-growing populations to among the most rapidly aging countries worldwide. In particular, the population of oldest-old individuals, those aged 80+, is projected to quadruple by 2050. The oldest-old represent a uniquely important group—they have high demand for personal assistance and the highest healthcare costs of any age group. Understanding trends in disability and longevity among the oldest-old—that is, whether successive generations are living longer and with less disability—is of great importance for policy and planning purposes. METHODS: We utilized data from successive birth cohorts (n = 20,520) of the Chinese oldest-old born 10 years apart (the earlier cohort was interviewed in 1998 and the later cohort in 2008). Disability was defined as needing personal assistance in performing one or more of five essential activities (bathing, transferring, dressing, eating, and toileting) or being incontinent. Participants were followed for age-specific disability transitions and mortality (in 2000 and 2002 for the earlier cohort and 2011 and 2014 for the later cohort), which were then used to generate microsimulation-based multistate life tables to estimate partial life expectancy (LE) and disability-free LE (DFLE), stratified by sex and age groups (octogenarians, nonagenarians, and centenarians). We additionally explored sociodemographic heterogeneity in LE and DFLE by urban/rural residence and educational attainment. RESULTS: More recently born Chinese octogenarians (born 1919–1928) had a longer partial LE between ages 80 and 89 than octogenarians born 1909–1918, and octogenarian women experienced an increase in partial DFLE of 0.32 years (P = 0.004) across the two birth cohorts. Although no increases in partial LE were observed among nonagenarians or centenarians, partial DFLE increased across birth cohorts, with a gain of 0.41 years (P < 0.001) among nonagenarians and 0.07 years (P = 0.050) among centenarians. Subgroup analyses revealed that gains in partial LE and DFLE primarily occurred among the urban resident population. CONCLUSIONS: Successive generations of China’s oldest-old are living with less disability as a whole, and LE is expanding among octogenarians. However, we found a widening urban-rural disparity in longevity and disability, highlighting the need to improve policies to alleviate health inequality throughout the population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12916-019-1259-z) contains supplementary material, which is available to authorized users.",2019 Feb 1,"['Liu, Zuyun', 'Han, Ling', 'Feng, Qiushi', 'Dupre, Matthew E.', 'Gu, Danan', 'Allore, Heather G.', 'Gill, Thomas M.', 'Payne, Collin F.']",BMC Med,,,True
26a222223bf9fe6164feaa2f4231923c9abcc77e,PMC,"Near-Complete Genome Sequence of Infectious Bronchitis Virus Strain VFAR-047 (GI-16 Lineage), Isolated in Peru",http://dx.doi.org/10.1128/MRA.01555-18,PMC6357641,30714035,CC BY,"Here, we report the near-complete genome sequence of the infectious bronchitis virus (IBV) strain VFAR-047, isolated in Peru in 2014. This strain was classified into GI lineage 16 (GI-16) based on both the genome and Spike 1 (S1) sequence analysis. Furthermore, four potential recombination events with other GI-16 and GI-11 strains were identified.",2019 Jan 31,"['Tataje-Lavanda, Luis', 'Izquierdo-Lara, Ray', 'Ormeño-Vásquez, Phillip', 'Huamán-Gutiérrez, Katherine', 'Zimic-Peralta, Mirko', 'Fernández-Díaz, Manolo']",Microbiol Resour Announc,,,True
c3617dc2a70b0046f95b857cb09cafeebf0a8ce4,PMC,Lassa virus diversity and feasibility for universal prophylactic vaccine,http://dx.doi.org/10.12688/f1000research.16989.1,PMC6357994,30774934,CC BY,"Lassa virus (LASV) is a highly prevalent mammarenavirus in West Africa and is maintained in nature in a persistently infected rodent host, Mastomys natalensis, which is widely spread in sub-Saharan Africa. LASV infection of humans can cause Lassa fever (LF), a disease associated with high morbidity and significant mortality. Recent evidence indicates an LASV expansion outside its traditional endemic areas. In 2017, the World Health Organization (WHO) included LASV in top-priority pathogens and released a Target Product Profile (TPP) for vaccine development. Likewise, in 2018, the US Food and Drug Administration added LF to a priority review voucher program to encourage the development of preventive and therapeutics measures. In this article, we review recent progress in LASV vaccine research and development with a focus on the impact of LASV genetic and biological diversity on the design and development of vaccine candidates meeting the WHO’s TPP for an LASV vaccine.",2019 Jan 31,"['Lukashevich, Igor S.', 'Paessler, Slobodan', 'de la Torre, Juan Carlos']",F1000Res,,,True
7b5d559562d07c48dfbba720712d27a53ee81504,PMC,In-plate recapturing of a dual-tagged recombinant Fasciola antigen (FhLAP) by a monoclonal antibody (US9) prevents non-specific binding in ELISA,http://dx.doi.org/10.1371/journal.pone.0211035,PMC6358068,30707711,CC BY,"Recombinant proteins expressed in E. coli are frequently purified by immobilized metal affinity chromatography (IMAC). By means of this technique, tagged proteins containing a polyhistidine sequence can be obtained up to 95% pure in a single step, but some host proteins also bind with great affinity to metal ions and contaminate the sample. A way to overcome this problem is to include a second tag that is recognized by a preexistent monoclonal antibody (mAb) in the gene encoding the target protein, allowing further purification. With this strategy, the recombinant protein can be directly used as target in capture ELISA using plates sensitized with the corresponding mAb. As a proof of concept, in this study we engineered a Trichinella-derived tag (MTFSVPIS, recognized by mAb US9) into a His-tagged recombinant Fasciola antigen (rFhLAP) to make a new chimeric recombinant protein (rUS9-FhLAP), and tested its specificity in capture and indirect ELISAs with sera from sheep and cattle. FhLAP was selected since it was previously reported to be immunogenic in ruminants and is expressed in soluble form in E. coli, which anticipates a higher contamination by host proteins than proteins expressed in inclusion bodies. Our results showed that a large number of sera from non-infected ruminants (mainly cattle) reacted in indirect ELISA with rUS9-FhLAP after single-step purification by IMAC, but that this reactivity disappeared testing the same antigen in capture ELISA with mAb US9. These results demonstrate that the 6XHis and US9 tags can be combined when double purification of recombinant proteins is required.",2019 Feb 1,"['Orbegozo-Medina, Ricardo A.', 'Martínez-Sernández, Victoria', 'Perteguer, María J.', 'Hernández-González, Ana', 'Mezo, Mercedes', 'González-Warleta, Marta', 'Romarís, Fernanda', 'Paniagua, Esperanza', 'Gárate, Teresa', 'Ubeira, Florencio M.']",PLoS One,,,True
5c21db27b83fa2b5d4c1b0739b99e53c83e0430c,PMC,Pelargonium sidoides radix extract EPs 7630 reduces rhinovirus infection through modulation of viral binding proteins on human bronchial epithelial cells,http://dx.doi.org/10.1371/journal.pone.0210702,PMC6358071,30707726,CC BY,"Bronchial epithelial cells are the first target cell for rhinovirus infection. The course of viral infections in patients with acute bronchitis, asthma and COPD can be improved by oral application of Pelargonium sidoides radix extract; however, the mechanism is not well understood. This study investigated the in vitro effect of Pelargonium sidoides radix extract (EPs 7630) on the expression of virus binding cell membrane and host defence supporting proteins on primary human bronchial epithelial cells (hBEC). Cells were isolated from patients with severe asthma (n = 6), moderate COPD (n = 6) and non-diseased controls (n = 6). Protein expression was determined by Western-blot and immunofluorescence. Rhinovirus infection was determined by immunofluorescence as well as by polymerase chain reaction. Cell survival was determined by manual cell count after live/death immunofluorescence staining. All parameters were determined over a period of 3 days. The results show that EPs 7630 concentration-dependently and significantly increased hBEC survival after rhinovirus infection. This effect was paralleled by decreased expression of the inducible co-stimulator (ICOS), its ligand ICOSL and cell surface calreticulin (C1qR). In contrast, EPs 7630 up-regulated the expression of the host defence supporting proteins β-defensin-1 and SOCS-1, both in rhinovirus infected and un-infected hBEC. The expression of other virus interacting cell membrane proteins such as MyD88, TRL2/4 or ICAM-1 was not altered by EPs 7630. The results indicate that EPs 7630 may reduce rhinovirus infection of human primary BEC by down-regulating cell membrane docking proteins and up-regulating host defence proteins.",2019 Feb 1,"['Roth, Michael', 'Fang, Lei', 'Stolz, Daiana', 'Tamm, Michael']",PLoS One,,,True
239981f0c8653119f1d300df15000f60c2ed1ad2,PMC,Pelargonium sidoides radix extract EPs 7630 reduces rhinovirus infection through modulation of viral binding proteins on human bronchial epithelial cells,http://dx.doi.org/10.1371/journal.pone.0210702,PMC6358071,30707726,CC BY,"Bronchial epithelial cells are the first target cell for rhinovirus infection. The course of viral infections in patients with acute bronchitis, asthma and COPD can be improved by oral application of Pelargonium sidoides radix extract; however, the mechanism is not well understood. This study investigated the in vitro effect of Pelargonium sidoides radix extract (EPs 7630) on the expression of virus binding cell membrane and host defence supporting proteins on primary human bronchial epithelial cells (hBEC). Cells were isolated from patients with severe asthma (n = 6), moderate COPD (n = 6) and non-diseased controls (n = 6). Protein expression was determined by Western-blot and immunofluorescence. Rhinovirus infection was determined by immunofluorescence as well as by polymerase chain reaction. Cell survival was determined by manual cell count after live/death immunofluorescence staining. All parameters were determined over a period of 3 days. The results show that EPs 7630 concentration-dependently and significantly increased hBEC survival after rhinovirus infection. This effect was paralleled by decreased expression of the inducible co-stimulator (ICOS), its ligand ICOSL and cell surface calreticulin (C1qR). In contrast, EPs 7630 up-regulated the expression of the host defence supporting proteins β-defensin-1 and SOCS-1, both in rhinovirus infected and un-infected hBEC. The expression of other virus interacting cell membrane proteins such as MyD88, TRL2/4 or ICAM-1 was not altered by EPs 7630. The results indicate that EPs 7630 may reduce rhinovirus infection of human primary BEC by down-regulating cell membrane docking proteins and up-regulating host defence proteins.",2019 Feb 1,"['Roth, Michael', 'Fang, Lei', 'Stolz, Daiana', 'Tamm, Michael']",PLoS One,,,False
dd601b6ee6e8b1711f78fe91b71b447258244432,PMC,Pelargonium sidoides radix extract EPs 7630 reduces rhinovirus infection through modulation of viral binding proteins on human bronchial epithelial cells,http://dx.doi.org/10.1371/journal.pone.0210702,PMC6358071,30707726,CC BY,"Bronchial epithelial cells are the first target cell for rhinovirus infection. The course of viral infections in patients with acute bronchitis, asthma and COPD can be improved by oral application of Pelargonium sidoides radix extract; however, the mechanism is not well understood. This study investigated the in vitro effect of Pelargonium sidoides radix extract (EPs 7630) on the expression of virus binding cell membrane and host defence supporting proteins on primary human bronchial epithelial cells (hBEC). Cells were isolated from patients with severe asthma (n = 6), moderate COPD (n = 6) and non-diseased controls (n = 6). Protein expression was determined by Western-blot and immunofluorescence. Rhinovirus infection was determined by immunofluorescence as well as by polymerase chain reaction. Cell survival was determined by manual cell count after live/death immunofluorescence staining. All parameters were determined over a period of 3 days. The results show that EPs 7630 concentration-dependently and significantly increased hBEC survival after rhinovirus infection. This effect was paralleled by decreased expression of the inducible co-stimulator (ICOS), its ligand ICOSL and cell surface calreticulin (C1qR). In contrast, EPs 7630 up-regulated the expression of the host defence supporting proteins β-defensin-1 and SOCS-1, both in rhinovirus infected and un-infected hBEC. The expression of other virus interacting cell membrane proteins such as MyD88, TRL2/4 or ICAM-1 was not altered by EPs 7630. The results indicate that EPs 7630 may reduce rhinovirus infection of human primary BEC by down-regulating cell membrane docking proteins and up-regulating host defence proteins.",2019 Feb 1,"['Roth, Michael', 'Fang, Lei', 'Stolz, Daiana', 'Tamm, Michael']",PLoS One,,,False
c806bb7d3d41181d66383906307af59935a174d8,PMC,Pelargonium sidoides radix extract EPs 7630 reduces rhinovirus infection through modulation of viral binding proteins on human bronchial epithelial cells,http://dx.doi.org/10.1371/journal.pone.0210702,PMC6358071,30707726,CC BY,"Bronchial epithelial cells are the first target cell for rhinovirus infection. The course of viral infections in patients with acute bronchitis, asthma and COPD can be improved by oral application of Pelargonium sidoides radix extract; however, the mechanism is not well understood. This study investigated the in vitro effect of Pelargonium sidoides radix extract (EPs 7630) on the expression of virus binding cell membrane and host defence supporting proteins on primary human bronchial epithelial cells (hBEC). Cells were isolated from patients with severe asthma (n = 6), moderate COPD (n = 6) and non-diseased controls (n = 6). Protein expression was determined by Western-blot and immunofluorescence. Rhinovirus infection was determined by immunofluorescence as well as by polymerase chain reaction. Cell survival was determined by manual cell count after live/death immunofluorescence staining. All parameters were determined over a period of 3 days. The results show that EPs 7630 concentration-dependently and significantly increased hBEC survival after rhinovirus infection. This effect was paralleled by decreased expression of the inducible co-stimulator (ICOS), its ligand ICOSL and cell surface calreticulin (C1qR). In contrast, EPs 7630 up-regulated the expression of the host defence supporting proteins β-defensin-1 and SOCS-1, both in rhinovirus infected and un-infected hBEC. The expression of other virus interacting cell membrane proteins such as MyD88, TRL2/4 or ICAM-1 was not altered by EPs 7630. The results indicate that EPs 7630 may reduce rhinovirus infection of human primary BEC by down-regulating cell membrane docking proteins and up-regulating host defence proteins.",2019 Feb 1,"['Roth, Michael', 'Fang, Lei', 'Stolz, Daiana', 'Tamm, Michael']",PLoS One,,,False
e64b3f4551c3fe6f27166b6ea2caaa5d6bbaf2e8,PMC,Pelargonium sidoides radix extract EPs 7630 reduces rhinovirus infection through modulation of viral binding proteins on human bronchial epithelial cells,http://dx.doi.org/10.1371/journal.pone.0210702,PMC6358071,30707726,CC BY,"Bronchial epithelial cells are the first target cell for rhinovirus infection. The course of viral infections in patients with acute bronchitis, asthma and COPD can be improved by oral application of Pelargonium sidoides radix extract; however, the mechanism is not well understood. This study investigated the in vitro effect of Pelargonium sidoides radix extract (EPs 7630) on the expression of virus binding cell membrane and host defence supporting proteins on primary human bronchial epithelial cells (hBEC). Cells were isolated from patients with severe asthma (n = 6), moderate COPD (n = 6) and non-diseased controls (n = 6). Protein expression was determined by Western-blot and immunofluorescence. Rhinovirus infection was determined by immunofluorescence as well as by polymerase chain reaction. Cell survival was determined by manual cell count after live/death immunofluorescence staining. All parameters were determined over a period of 3 days. The results show that EPs 7630 concentration-dependently and significantly increased hBEC survival after rhinovirus infection. This effect was paralleled by decreased expression of the inducible co-stimulator (ICOS), its ligand ICOSL and cell surface calreticulin (C1qR). In contrast, EPs 7630 up-regulated the expression of the host defence supporting proteins β-defensin-1 and SOCS-1, both in rhinovirus infected and un-infected hBEC. The expression of other virus interacting cell membrane proteins such as MyD88, TRL2/4 or ICAM-1 was not altered by EPs 7630. The results indicate that EPs 7630 may reduce rhinovirus infection of human primary BEC by down-regulating cell membrane docking proteins and up-regulating host defence proteins.",2019 Feb 1,"['Roth, Michael', 'Fang, Lei', 'Stolz, Daiana', 'Tamm, Michael']",PLoS One,,,False
709c639eadc0af409fb4f3c8f7e91bfc3917de67,PMC,Pelargonium sidoides radix extract EPs 7630 reduces rhinovirus infection through modulation of viral binding proteins on human bronchial epithelial cells,http://dx.doi.org/10.1371/journal.pone.0210702,PMC6358071,30707726,CC BY,"Bronchial epithelial cells are the first target cell for rhinovirus infection. The course of viral infections in patients with acute bronchitis, asthma and COPD can be improved by oral application of Pelargonium sidoides radix extract; however, the mechanism is not well understood. This study investigated the in vitro effect of Pelargonium sidoides radix extract (EPs 7630) on the expression of virus binding cell membrane and host defence supporting proteins on primary human bronchial epithelial cells (hBEC). Cells were isolated from patients with severe asthma (n = 6), moderate COPD (n = 6) and non-diseased controls (n = 6). Protein expression was determined by Western-blot and immunofluorescence. Rhinovirus infection was determined by immunofluorescence as well as by polymerase chain reaction. Cell survival was determined by manual cell count after live/death immunofluorescence staining. All parameters were determined over a period of 3 days. The results show that EPs 7630 concentration-dependently and significantly increased hBEC survival after rhinovirus infection. This effect was paralleled by decreased expression of the inducible co-stimulator (ICOS), its ligand ICOSL and cell surface calreticulin (C1qR). In contrast, EPs 7630 up-regulated the expression of the host defence supporting proteins β-defensin-1 and SOCS-1, both in rhinovirus infected and un-infected hBEC. The expression of other virus interacting cell membrane proteins such as MyD88, TRL2/4 or ICAM-1 was not altered by EPs 7630. The results indicate that EPs 7630 may reduce rhinovirus infection of human primary BEC by down-regulating cell membrane docking proteins and up-regulating host defence proteins.",2019 Feb 1,"['Roth, Michael', 'Fang, Lei', 'Stolz, Daiana', 'Tamm, Michael']",PLoS One,,,False
2284e4f1b99dd342353ec67249a0d6a78aa30c67,PMC,Pelargonium sidoides radix extract EPs 7630 reduces rhinovirus infection through modulation of viral binding proteins on human bronchial epithelial cells,http://dx.doi.org/10.1371/journal.pone.0210702,PMC6358071,30707726,CC BY,"Bronchial epithelial cells are the first target cell for rhinovirus infection. The course of viral infections in patients with acute bronchitis, asthma and COPD can be improved by oral application of Pelargonium sidoides radix extract; however, the mechanism is not well understood. This study investigated the in vitro effect of Pelargonium sidoides radix extract (EPs 7630) on the expression of virus binding cell membrane and host defence supporting proteins on primary human bronchial epithelial cells (hBEC). Cells were isolated from patients with severe asthma (n = 6), moderate COPD (n = 6) and non-diseased controls (n = 6). Protein expression was determined by Western-blot and immunofluorescence. Rhinovirus infection was determined by immunofluorescence as well as by polymerase chain reaction. Cell survival was determined by manual cell count after live/death immunofluorescence staining. All parameters were determined over a period of 3 days. The results show that EPs 7630 concentration-dependently and significantly increased hBEC survival after rhinovirus infection. This effect was paralleled by decreased expression of the inducible co-stimulator (ICOS), its ligand ICOSL and cell surface calreticulin (C1qR). In contrast, EPs 7630 up-regulated the expression of the host defence supporting proteins β-defensin-1 and SOCS-1, both in rhinovirus infected and un-infected hBEC. The expression of other virus interacting cell membrane proteins such as MyD88, TRL2/4 or ICAM-1 was not altered by EPs 7630. The results indicate that EPs 7630 may reduce rhinovirus infection of human primary BEC by down-regulating cell membrane docking proteins and up-regulating host defence proteins.",2019 Feb 1,"['Roth, Michael', 'Fang, Lei', 'Stolz, Daiana', 'Tamm, Michael']",PLoS One,,,False
53847cf95615b651c07388b52222211db0b4d303,PMC,"Seroprevalence, cross antigenicity and circulation sphere of bat-borne hantaviruses revealed by serological and antigenic analyses",http://dx.doi.org/10.1371/journal.ppat.1007545,PMC6358112,30668611,CC BY,"Bats are newly identified reservoirs of hantaviruses (HVs) among which very divergent HVs have been discovered in recent years. However, their significance for public health remains unclear since their seroprevalence as well as antigenic relationship with human-infecting HVs have not been investigated. In the present study archived tissues of 1,419 bats of 22 species from 6 families collected in 5 south and southwest provinces in China were screened by pan-HV RT-PCR following viral metagenomic analysis. As a result nine HVs have been identified in two bat species in two provinces and phylogenetically classified into two species, Laibin virus (LAIV, ICTV approved species, 1 strain) and Xuan son virus (XSV, proposed species, 8 strains). Additionally, 709 serum samples of these bats were also analyzed by ELISA to investigate the seroprevalence and cross-reactivity between different HVs using expressed recombinant nucleocapsid proteins (rNPs) of LAIV, XSV and Seoul virus (SEOV). The cross-reactivity of some bat sera were further confirmed by western blot (WB) using three rNPs followed by fluorescent antibody virus neutralization test (FAVNT) against live SEOV. Results showed that the total HV seropositive rate of bat sera was 18.5% (131/709) with many cross reacting with two or all three rNPs and several able to neutralize SEOV. WB analysis using the three rNPs and their specific hyperimmune sera demonstrated cross-reactivity between XSV/SEOV and LAIV/XSV, but not LAIV/SEOV, indicating that XSV is antigenically closer to human-infecting HVs. In addition a study of the distribution of the viruses identified an area covering the region between Chinese Guangxi and North Vietnam, in which XSV and LAIV circulate within different bat colonies with a high seroprevalence. A circulation sphere of bat-borne HVs has therefore been proposed.",2019 Jan 22,"['Xu, Lin', 'Wu, Jianmin', 'Li, Qi', 'Wei, Yamei', 'Tan, Zhizhou', 'Cai, Jianqiu', 'Guo, Huancheng', 'Yang, Ling’en', 'Huang, Xiaohong', 'Chen, Jing', 'Zhang, Fuqiang', 'He, Biao', 'Tu, Changchun']",PLoS Pathog,,,True
b0321c49afd322bf426b0dfb3eca1152a69ed168,PMC,Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling,http://dx.doi.org/10.3390/ijms20020239,PMC6358887,30634441,CC BY,"Apelin is an inotropic and cardioprotective peptide that exhibits beneficial effects through activation of the APJ receptor in the pathology of cardiovascular diseases. Apelin induces the expression of angiotensin-converting enzyme 2 (ACE2) in failing hearts, thereby improving heart function in an angiotensin 1–7-dependent manner. Whether apelin antagonizes the over-activation of the renin–angiotensin system in the heart remains elusive. In this study we show that the detrimental effects of angiotensin II (Ang II) were exacerbated in the hearts of aged apelin-gene-deficient mice. Ang II-mediated cardiac dysfunction and hypertrophy were augmented in apelin knockout mice. The loss of apelin increased the ratio of angiotensin-converting enzyme (ACE) to ACE2 expression in the Ang II-stressed hearts, and Ang II-induced cardiac fibrosis was markedly enhanced in apelin knockout mice. mRNA expression of pro-fibrotic genes, such as transforming growth-factor beta (TGF-β) signaling, were significantly upregulated in apelin knockout hearts. Consistently, treatment with the ACE-inhibitor Captopril decreased cardiac contractility in apelin knockout mice. In vitro, apelin ameliorated Ang II-induced TGF-β expression in primary cardiomyocytes, accompanied with reduced hypertrophy. These results provide direct evidence that endogenous apelin plays a crucial role in suppressing Ang II-induced cardiac dysfunction and pathological remodeling.",2019 Jan 9,"['Sato, Teruki', 'Kadowaki, Ayumi', 'Suzuki, Takashi', 'Ito, Hiroshi', 'Watanabe, Hiroyuki', 'Imai, Yumiko', 'Kuba, Keiji']",Int J Mol Sci,,,True
90bde77361b9b5b1275ce44a238f619aef04483f,PMC,Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling,http://dx.doi.org/10.3390/ijms20020239,PMC6358887,30634441,CC BY,"Apelin is an inotropic and cardioprotective peptide that exhibits beneficial effects through activation of the APJ receptor in the pathology of cardiovascular diseases. Apelin induces the expression of angiotensin-converting enzyme 2 (ACE2) in failing hearts, thereby improving heart function in an angiotensin 1–7-dependent manner. Whether apelin antagonizes the over-activation of the renin–angiotensin system in the heart remains elusive. In this study we show that the detrimental effects of angiotensin II (Ang II) were exacerbated in the hearts of aged apelin-gene-deficient mice. Ang II-mediated cardiac dysfunction and hypertrophy were augmented in apelin knockout mice. The loss of apelin increased the ratio of angiotensin-converting enzyme (ACE) to ACE2 expression in the Ang II-stressed hearts, and Ang II-induced cardiac fibrosis was markedly enhanced in apelin knockout mice. mRNA expression of pro-fibrotic genes, such as transforming growth-factor beta (TGF-β) signaling, were significantly upregulated in apelin knockout hearts. Consistently, treatment with the ACE-inhibitor Captopril decreased cardiac contractility in apelin knockout mice. In vitro, apelin ameliorated Ang II-induced TGF-β expression in primary cardiomyocytes, accompanied with reduced hypertrophy. These results provide direct evidence that endogenous apelin plays a crucial role in suppressing Ang II-induced cardiac dysfunction and pathological remodeling.",2019 Jan 9,"['Sato, Teruki', 'Kadowaki, Ayumi', 'Suzuki, Takashi', 'Ito, Hiroshi', 'Watanabe, Hiroyuki', 'Imai, Yumiko', 'Kuba, Keiji']",Int J Mol Sci,,,False
fe14106f9f3d2b3b6d8ea619cfcc4363148dc84b,PMC,Immune response development after vaccination of 1-day-old naïve pigs with a Porcine Reproductive and Respiratory Syndrome 1-based modified live virus vaccine,http://dx.doi.org/10.1186/s40813-018-0112-7,PMC6359793,30761215,CC BY,"BACKGROUND: The development of the innate and adaptive immune responses to Porcine reproductive and respiratory syndrome virus (PRRSV) after vaccination of 1 day-old pigs with a PRRSV-1 based modified live virus (MLV) vaccine by intramuscular (IM) and intranasal (IN) routes was characterised, before and after challenge with a heterologous PRRSV-1 isolate at 18 weeks post-vaccination. Twenty-five PRRSV-seronegative piglets were used. At 1 day of age, pigs were administered with a single dose of vaccine via the IM (n = 10) or the IN route (n = 10). Control group (n = 5) received saline solution. After vaccination, pigs were bled at days 3, 7, 28, 56, 83, 113 and 125. Levels of cytokines IL-10, IL-8, IFN-α (measured by ELISA tests of serum), TNF-α and IFN-γ (measured by ELISA and ELISPOT, respectively, from stimulated peripheral blood mononuclear cells), and serum neutralising antibodies (NA) to the vaccine strain, were measured. RESULTS: The induction of IL-10 was rare, indicating that IL-10 mediated immunomodulation/immune dysfunction was not a feature of this vaccine or of the challenge virus. IL-8 was detected in only two pigs following vaccination, but in the majority of pigs after challenge, indicating that their ability to produce an innate immune response was not impaired. TNF-α was not detected in any vaccinated pigs until day 83. After challenge, only a minority of pigs produced TNF-α. IFN-α was detected in all vaccinated pigs following vaccination, indicating the potential for development of an effective Th1 adaptive immune response. IFN-γ-secreting cells were detected in all vaccinated pigs after vaccination. NA to the vaccine strain were first detected at day 56 in pigs vaccinated by both routes, and remained at similar levels until challenge. After challenge, a boost in NA was observed. The efficacy of the vaccine was demonstrated by reduction of viraemia and nasal shedding after challenge. CONCLUSIONS: The administration of a PRRSV-1 based MLV vaccine to 1 day-old piglets was able to induce an immune response characterised by: (1) undetectable or low levels of IL-10, IL-8 and TNF-α, (2) an increase in IFN-α expression within the first seven days, (3) a gradual increase in the number of antigen-specific IFN-γ-secreting cells, and (4) induction of detectable NA. After challenge with a heterologous strain, there was a rapid boost in NA titres, indicating a priming effect of the vaccine.",2019 Feb 2,"['Balasch, Monica', 'Fort, Maria', 'Taylor, Lucas P.', 'Díaz, Ivan', 'Mateu, Enric', 'Calvert, Jay G.']",Porcine Health Manag,,,True
43d4ca7da86537799185698ae3463b736bc56fc1,PMC,A radical form of nitric oxide inhibits porcine circovirus type 2 replication in vitro,http://dx.doi.org/10.1186/s12917-019-1796-x,PMC6359798,30709350,CC BY,"BACKGROUND: Porcine circovirus type 2 (PCV2) is the causal agent of postweaning multisystemic wasting syndrome (PMWS), causing large economical losses of the global swine industry. Nitric oxide (NO), as an important signaling molecule, has antiviral activity on some viruses. To date, there is little information on the role of NO during PCV2 infection. RESULTS: We used indirect fluorescence assay (IFA), TCID(50), real-time RT-qPCR and western blot assay to reveal the role of NO in restricting PCV2 replication. PCV2 replication was inhibited by a form of NO, NO(•), whereas PCV2 was not susceptible to another form of NO, NO(+). CONCLUSION: Our findings indicate that the form of NO(•) has a potential role in the fight against PCV2 infection.",2019 Feb 1,"['Xue, Tao', 'Li, Jizong', 'Liu, Chuanmin']",BMC Vet Res,,,True
233b6a7c5234ef4a8bb7918dab6d5ea8fe0b1aad,PMC,Nasopharyngeal Microbiota in Children With Invasive Pneumococcal Disease: Identification of Bacteria With Potential Disease-Promoting and Protective Effects,http://dx.doi.org/10.3389/fmicb.2019.00011,PMC6360994,30745895,CC BY,"Background and Aims: The risk of suffering from some infectious diseases can be related to specific microbiota profiles. Specifically, the nasopharyngeal microbiota could play a role as a risk or protective factor in the development of invasive disease caused by S. pneumoniae. Methodology: We analyzed the nasopharyngeal microbiota of children with invasive pneumococcal disease (IPD) and that of healthy controls matched by age, sex, and seasonality from Catalonia, Spain. Epidemiological, microbiological and clinical variables were considered to compare microbiota profiles, analyzed by sequencing the V1–V4 region of the 16S rRNA gene. Results: Twenty-eight children with IPD (median age 43 months) and 28 controls (42.6 months) were included in the study. IPD children presented a significantly higher bacterial diversity and richness (p < 0.001). Principal coordinate analysis revealed three different microbiota profiles: microbiota A, dominated by the genus Dolosigranulum (44.3%); Microbiota B, mostly represented by Streptococcus (36.9%) and Staphylococcus (21.3%) and a high diversity of anaerobic genera including Veillonella, Prevotella and Porphyromonas; and Microbiota C, mainly containing Haemophilus (52.1%) and Moraxella (31.4%). The only explanatory factor for the three microbiotas was the classification of children into disease or healthy controls (p = 0.006). A significant negative correlation was found between Dolosigranulum vs. Streptococcus (p = 0.029), suggesting a potential antagonistic effect against pneumococcal pathogens. Conclusions: The higher bacterial diversity and richness in children with IPD could suggest an impaired immune response. This lack of immune competence could be aggravated by breastfeeding <6 months and by the presence of keystone pathogens such as Porphyromonas, a bacterium which has been shown to be able to manipulate the immune response, and that could favor the overgrowth of many proteolytic anaerobic organisms giving rise to a dramatic dysbiosis. From an applied viewpoint, we found suggestive microbiota profiles associated to IPD or asymptomatic colonization that could be used as disease biomarkers or to pave the way for characterizing health-associated inhabitants of the respiratory tract. The identification of beneficial bacteria could be useful to prevent pneumococcal infections by integrating those microorganisms in a probiotic formula. The present study suggests not only respiratory tract samples, but also breast milk, as a potential source of those beneficial bacteria.",2019 Jan 28,"['Camelo-Castillo, Anny', 'Henares, Desirée', 'Brotons, Pedro', 'Galiana, Antonio', 'Rodríguez, Juan Carlos', 'Mira, Alex', 'Muñoz-Almagro, Carmen']",Front Microbiol,,,True
24db4d088787fb5c43f2f60604e1f1463d4b4082,PMC,Development and characterization of a new cell line derived from European eel Anguilla anguilla kidney,http://dx.doi.org/10.1242/bio.037507,PMC6361207,30429125,CC BY,"A new cell line derived from the kidney of European eel, Anguilla anguilla, has been established and characterized. This cell line, designated as EK (eel kidney), has been maintained in Leibovitz's L-15 supplemented with 10% fetal bovine serum for over 24 months, and subcultured more than 60 times. This cell line consists predominantly of fibroblast-like cells, and can grow at 15–37°C under an optimum temperature of 26°C. The origin of this cell line was confirmed by polymerase chain reaction (PCR) amplification and 18s recombinant (r)RNA sequencing. The chromosome analysis of EK cells at passage 58 revealed an ananeuploid karyotype. The EK cells were successfully transfected with the Pegfp-N1 plasmid, suggesting its potential in genetic studies. The susceptibility test showed a significant cytopathic effect (CPE) in EK cells for Rana grylio virus, and the viral replication was evidenced with quantitative real-time PCR (qRT-PCR) assay. After poly (I:C) stimulation, the expression of the immune-related molecules including interferon regulatory factor-3 (irf3), interferon regulatory factor-7 (irf7) and cytochrome P450 (CYP450) were significantly upregulated in EK cells, while the expression of transforming growth factor (TGF-β) was downregulated. These results suggested the potential of EK cell line as a model in gene engineering, virus identification and environmental toxicology.",2018 Nov 14,"['Chen, Bin', 'Zheng, Zaiyu', 'Yang, Jinxian', 'Chi, Hongshu', 'Huang, He', 'Gong, Hui']",Biol Open,,,True
66106c89f2c46189df8716d74392a61c6f034585,PMC,Development and characterization of a new cell line derived from European eel Anguilla anguilla kidney,http://dx.doi.org/10.1242/bio.037507,PMC6361207,30429125,CC BY,"A new cell line derived from the kidney of European eel, Anguilla anguilla, has been established and characterized. This cell line, designated as EK (eel kidney), has been maintained in Leibovitz's L-15 supplemented with 10% fetal bovine serum for over 24 months, and subcultured more than 60 times. This cell line consists predominantly of fibroblast-like cells, and can grow at 15–37°C under an optimum temperature of 26°C. The origin of this cell line was confirmed by polymerase chain reaction (PCR) amplification and 18s recombinant (r)RNA sequencing. The chromosome analysis of EK cells at passage 58 revealed an ananeuploid karyotype. The EK cells were successfully transfected with the Pegfp-N1 plasmid, suggesting its potential in genetic studies. The susceptibility test showed a significant cytopathic effect (CPE) in EK cells for Rana grylio virus, and the viral replication was evidenced with quantitative real-time PCR (qRT-PCR) assay. After poly (I:C) stimulation, the expression of the immune-related molecules including interferon regulatory factor-3 (irf3), interferon regulatory factor-7 (irf7) and cytochrome P450 (CYP450) were significantly upregulated in EK cells, while the expression of transforming growth factor (TGF-β) was downregulated. These results suggested the potential of EK cell line as a model in gene engineering, virus identification and environmental toxicology.",2018 Nov 14,"['Chen, Bin', 'Zheng, Zaiyu', 'Yang, Jinxian', 'Chi, Hongshu', 'Huang, He', 'Gong, Hui']",Biol Open,,,False
a950b2355ef4a4ab294862a26fff70d090a81d6c,PMC,"SKEMPI 2.0: an updated benchmark of changes in protein–protein binding energy, kinetics and thermodynamics upon mutation",http://dx.doi.org/10.1093/bioinformatics/bty635,PMC6361233,30020414,CC BY,"MOTIVATION: Understanding the relationship between the sequence, structure, binding energy, binding kinetics and binding thermodynamics of protein–protein interactions is crucial to understanding cellular signaling, the assembly and regulation of molecular complexes, the mechanisms through which mutations lead to disease, and protein engineering. RESULTS: We present SKEMPI 2.0, a major update to our database of binding free energy changes upon mutation for structurally resolved protein–protein interactions. This version now contains manually curated binding data for 7085 mutations, an increase of 133%, including changes in kinetics for 1844 mutations, enthalpy and entropy changes for 443 mutations, and 440 mutations, which abolish detectable binding. AVAILABILITY AND IMPLEMENTATION: The database is available as supplementary data and at https://life.bsc.es/pid/skempi2/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.",2019 Feb 1,"['Jankauskaitė, Justina', 'Jiménez-García, Brian', 'Dapkūnas, Justas', 'Fernández-Recio, Juan', 'Moal, Iain H']",Bioinformatics,,,True
17e4de7b95ed440d0df3a87e85e9fca8b64b0de7,PMC,Incorporating media data into a model of infectious disease transmission,http://dx.doi.org/10.1371/journal.pone.0197646,PMC6361417,30716139,CC BY,"Understanding the effect of media on disease spread can help improve epidemic forecasting and uncover preventive measures to slow the spread of disease. Most previously introduced models have approximated media effect through disease incidence, making media influence dependent on the size of epidemic. We propose an alternative approach, which relies on real data about disease coverage in the news, allowing us to model low incidence/high interest diseases, such as SARS, Ebola or H1N1. We introduce a network-based model, in which disease is transmitted through local interactions between individuals and the probability of transmission is affected by media coverage. We assume that media attention increases self-protection (e.g. hand washing and compliance with social distancing), which, in turn, decreases disease model. We apply the model to the case of H1N1 transmission in Mexico City in 2009 and show how media influence—measured by the time series of the weekly count of news articles published on the outbreak—helps to explain the observed transmission dynamics. We show that incorporating the media attention based on the observed media coverage of the outbreak better estimates the disease dynamics from what would be predicted by using media function that approximate the media impact using the number of cases and rate of spread. Finally, we apply the model to a typical influenza season in Washington, DC and estimate how the transmission pattern would have changed given different levels of media coverage.",2019 Feb 4,"['Kim, Louis', 'Fast, Shannon M.', 'Markuzon, Natasha']",PLoS One,,,True
87810195a429d5f1d8b494f1170c9e82bc24f9a1,PMC,"Point-Of-Care Testing Curriculum and Accreditation for Public Health—Enabling Preparedness, Response, and Higher Standards of Care at Points of Need",http://dx.doi.org/10.3389/fpubh.2018.00385,PMC6361824,30761282,CC BY,"Objectives: To develop awareness of benefits of point-of-care testing (POCT) education in schools of public health, to identify learning objectives for teaching POCT, to enable public health professionals and emergency responders to perform evidence-based diagnosis and triage effectively and efficiently at points of need, and to better improve future standards of care for public health practice, including in limited-resource settings and crisis situations. Methods: We surveyed all U.S. schools of public health, colleges of public health, and public health schools accredited by the Council on Education in Public Health (CEPH). We included accredited public health programs, so that all states offering public health education were represented. We analyzed survey data, public health books, and board certification guidelines. We used PubMed to identify public health curriculum papers, and assessed 2019 CEPH accreditation requirements. We merged POCT knowledge bases to design a new curriculum for teaching public health students and practitioners the principles and practice of POCT. Results: Public health curricula, certification requirements, and textbooks generally do not include POCT instruction. Only one book, Global Point of Care: Strategies for Disasters, Emergencies, and Public Health Resilience, and one online course on public health preparedness address POCT and public health intervention issues. The topic, POC HIV/HCV ED testing, appeared in one course and POC diagnostics in local clinics, in another. Papers on public health curriculum have not incorporated POCT. No curriculum addresses POCT in isolation units during quarantine, despite evidence that recent Ebola virus disease cases in the U.S. and elsewhere proved unequivocally the need for POCT. The modular learning objectives identified in this paper were customized for public health students. Public health graduates can use boot camps, online credentialing, and self-study to acquire POCT skills. Conclusions: Enhancing accreditation requirements, academic training, board certification, and field experience will generate public health healthcare professionals who will rely upon evidence-based medical decision making at points of care, including during crises when time is of the essence. A POCT-enabled public health workforce can help prevent and stop outbreaks. Public health-based medical professionals urgently need the skills necessary to perform POCT and prepare America and other nations for threats portending significant adverse medical, economic, social, and cultural impact.",2019 Jan 29,"['Kost, Gerald J.', 'Zadran, A.', 'Zadran, L.', 'Ventura, I.']",Front Public Health,,,True
f02d0c1e8b0109648e578662dc250abe349a033c,PMC,Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome,http://dx.doi.org/10.3389/fmicb.2019.00050,PMC6361828,30761102,CC BY,"Nod-like receptor family, pyrin domain-containing 3 (NLRP3) regulates the secretion of proinflammatory cytokines interleukin 1 beta (IL-1β) and IL-18. We previously showed that influenza virus M2 or encephalomyocarditis virus (EMCV) 2B proteins stimulate IL-1β secretion following activation of the NLRP3 inflammasome. However, the mechanism by which severe acute respiratory syndrome coronavirus (SARS-CoV) activates the NLRP3 inflammasome remains unknown. Here, we provide direct evidence that SARS-CoV 3a protein activates the NLRP3 inflammasome in lipopolysaccharide-primed macrophages. SARS-CoV 3a was sufficient to cause the NLRP3 inflammasome activation. The ion channel activity of the 3a protein was essential for 3a-mediated IL-1β secretion. While cells uninfected or infected with a lentivirus expressing a 3a protein defective in ion channel activity expressed NLRP3 uniformly throughout the cytoplasm, NLRP3 was redistributed to the perinuclear space in cells infected with a lentivirus expressing the 3a protein. K(+) efflux and mitochondrial reactive oxygen species were important for SARS-CoV 3a-induced NLRP3 inflammasome activation. These results highlight the importance of viroporins, transmembrane pore-forming viral proteins, in virus-induced NLRP3 inflammasome activation.",2019 Jan 29,"['Chen, I-Yin', 'Moriyama, Miyu', 'Chang, Ming-Fu', 'Ichinohe, Takeshi']",Front Microbiol,,,True
3c93efd2cee508cb7d0eb6f77bdd42c959c75da1,PMC,Real-time analysis of quantum dot labeled single porcine epidemic diarrhea virus moving along the microtubules using single particle tracking,http://dx.doi.org/10.1038/s41598-018-37789-9,PMC6362069,30718724,CC BY,"In order to study the infection mechanism of porcine epidemic diarrhea virus (PEDV), which causes porcine epidemic diarrhea, a highly contagious enteric disease, we combined quantum dot labeled method, which could hold intact infectivity of the labeled viruses to the largest extent, with the single particle tracking technique to dynamically and globally visualize the transport behaviors of PEDVs in live Vero cells. Our results were the first time to uncover the dynamic characteristics of PEDVs moving along the microtubules in the host cells. It is found that PEDVs kept restricted motion mode with a relatively stable speed in the cell membrane region; while performed a slow-fast-slow velocity pattern with different motion modes in the cell cytoplasm region and near the microtubule organizing center region. In addition, the return movements of small amount of PEDVs were also observed in the live cells. Collectively, our work is crucial for understanding the movement mechanisms of PEDV in the live cells, and the proposed work also provided important references for further analysis and study on the infection mechanism of PEDVs.",2019 Feb 4,"['Hou, Wei', 'Li, Yangyang', 'Kang, Wenjie', 'Wang, Xin', 'Wu, Xuping', 'Wang, Shouyu', 'Liu, Fei']",Sci Rep,,,False
d91c2ac8b93129970cedf7baaf3688e8026c2ca4,PMC,Real-time analysis of quantum dot labeled single porcine epidemic diarrhea virus moving along the microtubules using single particle tracking,http://dx.doi.org/10.1038/s41598-018-37789-9,PMC6362069,30718724,CC BY,"In order to study the infection mechanism of porcine epidemic diarrhea virus (PEDV), which causes porcine epidemic diarrhea, a highly contagious enteric disease, we combined quantum dot labeled method, which could hold intact infectivity of the labeled viruses to the largest extent, with the single particle tracking technique to dynamically and globally visualize the transport behaviors of PEDVs in live Vero cells. Our results were the first time to uncover the dynamic characteristics of PEDVs moving along the microtubules in the host cells. It is found that PEDVs kept restricted motion mode with a relatively stable speed in the cell membrane region; while performed a slow-fast-slow velocity pattern with different motion modes in the cell cytoplasm region and near the microtubule organizing center region. In addition, the return movements of small amount of PEDVs were also observed in the live cells. Collectively, our work is crucial for understanding the movement mechanisms of PEDV in the live cells, and the proposed work also provided important references for further analysis and study on the infection mechanism of PEDVs.",2019 Feb 4,"['Hou, Wei', 'Li, Yangyang', 'Kang, Wenjie', 'Wang, Xin', 'Wu, Xuping', 'Wang, Shouyu', 'Liu, Fei']",Sci Rep,,,True
a6156979e95c44541bc7fe236a1285161b77794a,PMC,Development and Evaluation of a Multiplexed Immunoassay for Simultaneous Detection of Serum IgG Antibodies to Six Human Coronaviruses,http://dx.doi.org/10.1038/s41598-018-37747-5,PMC6362100,30718599,CC BY,"Known human coronaviruses (hCoV) usually cause mild to moderate upper-respiratory tract illnesses, except SARS-CoV and MERS-CoV, which, in addition to mild illness can also be associated with severe respiratory diseases and high mortality rates. Well-characterized multiplexed serologic assays are needed to aid in rapid detection and surveillance of hCoVs. The present study describes development and evaluation of a multiplexed magnetic microsphere immunoassay (MMIA) to simultaneously detect immunoglobulin G (IgG) antibodies specific for recombinant nucleocapsid proteins (recN) from hCoVs 229E, NL63, OC43, HKU1, SARS-CoV, and MERS-CoV. We used paired human sera to screen for IgG with reactivity against six hCoVs to determine assay sensitivity, specificity and reproducibility. We found no signal interference between monoplex and multiplex assay formats (R(2) range = 0.87–0.97). Screening of paired human sera using MMIA, resulted in 92 of 106 (sensitivity: 86%) as positive and 68 of 80 (specificity: 84%) as negative. This study serves as a proof of concept that it is feasible to develop and use a multiplexed microsphere immunoassay as a next generation screening tool for use in large scale seroprevalence studies of hCoVs.",2019 Feb 4,"['Trivedi, Suvang U.', 'Miao, Congrong', 'Sanchez, Joseph E.', 'Caidi, Hayat', 'Tamin, Azaibi', 'Haynes, Lia', 'Thornburg, Natalie J.']",Sci Rep,,,True
056436a3b987b7d58290b79f35df450e7417f73c,PMC,Generation of bat-derived influenza viruses and their reassortants,http://dx.doi.org/10.1038/s41598-018-37830-x,PMC6362294,30718752,CC BY,"Two novel influenza A virus-like genomes were detected in fruit bats in Central and South America. However, the biological properties of these bat-derived influenza viruses (BatIVs) are still largely unknown since infectious viral particles have never been isolated from the infected host species. In this study, a reverse genetics approach was used to generate infectious BatIV particles entirely from plasmids encoding full-length sequences in eight gene segments. We inoculated BatIV particles into various cell cultures including bat-derived cell lines and found that BatIVs infected particular bat-derived cells efficiently but not the other cell lines tested. Reassortant viruses between the two BatIVs were also successfully generated and their replication in the susceptible bat cell lines was confirmed. These findings suggest a limited host range and reassortment potential of BatIVs in nature, providing fundamental information for understanding of the ecology of BatIVs.",2019 Feb 4,"['Sato, Masahiro', 'Maruyama, Junki', 'Kondoh, Tatsunari', 'Nao, Naganori', 'Miyamoto, Hiroko', 'Takadate, Yoshihiro', 'Furuyama, Wakako', 'Kajihara, Masahiro', 'Ogawa, Hirohito', 'Manzoor, Rashid', 'Yoshida, Reiko', 'Igarashi, Manabu', 'Takada, Ayato']",Sci Rep,,,False
90b43fc0b556b97bcc6ccc57f87f4e2811e0d4ed,PMC,Generation of bat-derived influenza viruses and their reassortants,http://dx.doi.org/10.1038/s41598-018-37830-x,PMC6362294,30718752,CC BY,"Two novel influenza A virus-like genomes were detected in fruit bats in Central and South America. However, the biological properties of these bat-derived influenza viruses (BatIVs) are still largely unknown since infectious viral particles have never been isolated from the infected host species. In this study, a reverse genetics approach was used to generate infectious BatIV particles entirely from plasmids encoding full-length sequences in eight gene segments. We inoculated BatIV particles into various cell cultures including bat-derived cell lines and found that BatIVs infected particular bat-derived cells efficiently but not the other cell lines tested. Reassortant viruses between the two BatIVs were also successfully generated and their replication in the susceptible bat cell lines was confirmed. These findings suggest a limited host range and reassortment potential of BatIVs in nature, providing fundamental information for understanding of the ecology of BatIVs.",2019 Feb 4,"['Sato, Masahiro', 'Maruyama, Junki', 'Kondoh, Tatsunari', 'Nao, Naganori', 'Miyamoto, Hiroko', 'Takadate, Yoshihiro', 'Furuyama, Wakako', 'Kajihara, Masahiro', 'Ogawa, Hirohito', 'Manzoor, Rashid', 'Yoshida, Reiko', 'Igarashi, Manabu', 'Takada, Ayato']",Sci Rep,,,True
0dc958db13e5ac3b76b8204a8081ad0cec38bcfa,PMC,Identification of Potential Type II Diabetes in a Chinese Population with a Sensitive Decision Tree Approach,http://dx.doi.org/10.1155/2019/4248218,PMC6362481,30805372,CC BY,"BACKGROUND: Diabetes mellitus is a chronic disease with a steadfast increase in prevalence. Due to the chronic course of the disease combining with devastating complications, this disorder could easily carry a financial burden. The early diagnosis of diabetes remains as one of the major challenges medical providers are facing, and the satisfactory screening tools or methods are still required, especially a population- or community-based tool. METHODS: This is a retrospective cross-sectional study involving 15,323 subjects who underwent the annual check-up in the Department of Family Medicine of Shengjing Hospital of China Medical University from January 2017 to June 2017. With a strict data filtration, 10,436 records from the eligible participants were utilized to develop a prediction model using the J48 decision tree algorithm. Nine variables, including age, gender, body mass index (BMI), hypertension, history of cardiovascular disease or stroke, family history of diabetes, physical activity, work-related stress, and salty food preference, were considered. RESULTS: The accuracy, precision, recall, and area under the receiver operating characteristic curve (AUC) value for identifying potential diabetes were 94.2%, 94.0%, 94.2%, and 94.8%, respectively. The structure of the decision tree shows that age is the most significant feature. The decision tree demonstrated that among those participants with age ≤ 49, 5497 participants (97%) of the individuals were identified as nondiabetic, while age > 49, 771 participants (50%) of the individuals were identified as nondiabetic. In the subgroup where people were 34 < age ≤ 49 and BMI ≥ 25, when with positive family history of diabetes, 89 (92%) out of 97 individuals were identified as diabetic and, when without family history of diabetes, 576 (58%) of the individuals were identified as nondiabetic. Work-related stress was identified as being associated with diabetes. In individuals with 34 < age ≤ 49 and BMI ≥ 25 and without family history of diabetes, 22 (51%) of the individuals with high work-related stress were identified as nondiabetic while 349 (88%) of the individuals with low or moderate work-related stress were identified as not having diabetes. CONCLUSIONS: We proposed a classifier based on a decision tree which used nine features of patients which are easily obtained and noninvasive as predictor variables to identify potential incidents of diabetes. The classifier indicates that a decision tree analysis can be successfully applied to screen diabetes, which will support clinical practitioners for rapid diabetes identification. The model provides a means to target the prevention of diabetes which could reduce the burden on the health system through effective case management.",2019 Jan 22,"['Pei, Dongmei', 'Zhang, Chengpu', 'Quan, Yu', 'Guo, Qiyong']",J Diabetes Res,,,True
4e69eb0c40279678624a4085b3544199d0f5b712,PMC,A case-crossover analysis of the impact of weather on primary cases of Middle East respiratory syndrome,http://dx.doi.org/10.1186/s12879-019-3729-5,PMC6362578,30717685,CC BY,"BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic in dromedary camels in the Arabian Peninsula, and zoonotic transmission to people is a sporadic event. In the absence of epidemiological data on the reservoir species, patterns of zoonotic transmission have largely been approximated from primary human cases. This study aimed to identify meteorological factors that may increase the risk of primary MERS infections in humans. METHODS: A case-crossover design was used to identify associations between primary MERS cases and preceding weather conditions within the 2-week incubation period in Saudi Arabia using univariable conditional logistic regression. Cases with symptom onset between January 2015 – December 2017 were obtained from a publicly available line list of human MERS cases maintained by the World Health Organization. The complete case dataset (N = 1191) was reduced to approximate the cases most likely to represent spillover transmission from camels (N = 446). Data from meteorological stations closest to the largest city in each province were used to calculate the daily mean, minimum, and maximum temperature ((ο)C), relative humidity (%), wind speed (m/s), and visibility (m). Weather variables were categorized according to strata; temperature and humidity into tertiles, and visibility and wind speed into halves. RESULTS: Lowest temperature (Odds Ratio = 1.27; 95% Confidence Interval = 1.04–1.56) and humidity (OR = 1.35; 95% CI = 1.10–1.65) were associated with increased cases 8–10 days later. High visibility was associated with an increased number of cases 7 days later (OR = 1.26; 95% CI = 1.01–1.57), while wind speed also showed statistically significant associations with cases 5–6 days later. CONCLUSIONS: Results suggest that primary MERS human cases in Saudi Arabia are more likely to occur when conditions are relatively cold and dry. This is similar to seasonal patterns that have been described for other respiratory diseases in temperate climates. It was hypothesized that low visibility would be positively associated with primary cases of MERS, however the opposite relationship was seen. This may reflect behavioural changes in different weather conditions. This analysis provides key initial evidence of an environmental component contributing to the development of primary MERS-CoV infections.",2019 Feb 4,"['Gardner, Emma G.', 'Kelton, David', 'Poljak, Zvonimir', 'Van Kerkhove, Maria', 'von Dobschuetz, Sophie', 'Greer, Amy L.']",BMC Infect Dis,,,True
2c6d57a5c31e345cd689687255b13506d71df902,PMC,Early Porcine Sapovirus Infection Disrupts Tight Junctions and Uses Occludin as a Coreceptor,http://dx.doi.org/10.1128/JVI.01773-18,PMC6364031,30463963,CC BY,"The genus Sapovirus belongs to the family Caliciviridae, and its members are common causative agents of severe acute gastroenteritis in both humans and animals. Some caliciviruses are known to use either terminal sialic acids or histo-blood group antigens as attachment factors and/or cell surface proteins, such as CD300lf, CD300ld, and junctional adhesion molecule 1 of tight junctions (TJs), as receptors. However, the roles of TJs and their proteins in sapovirus entry have not been examined. In this study, we found that porcine sapovirus (PSaV) significantly decreased transepithelial electrical resistance and increased paracellular permeability early in infection of LLC-PK cells, suggesting that PSaV dissociates TJs of cells. This led to the interaction between PSaV particles and occludin, which traveled in a complex into late endosomes via Rab5- and Rab7-dependent trafficking. Inhibition of occludin using small interfering RNA (siRNA), a specific antibody, or a dominant-negative mutant significantly blocked the entry of PSaV. Transient expression of occludin in nonpermissive Chinese hamster ovary (CHO) cells conferred susceptibility to PSaV, but only for a limited time. Although claudin-1, another TJ protein, neither directly interacted nor was internalized with PSaV particles, it facilitated PSaV entry and replication in the LLC-PK cells. We conclude that PSaV particles enter LLC-PK cells by binding to occludin as a coreceptor in PSaV-dissociated TJs. PSaV and occludin then form a complex that moves to late endosomes via Rab5- and Rab7-dependent trafficking. In addition, claudin-1 in the TJs opened by PSaV infection facilitates PSaV entry and infection as an entry factor. IMPORTANCE Sapoviruses (SaVs) cause severe acute gastroenteritis in humans and animals. Although they replicate in intestinal epithelial cells, which are tightly sealed by apical-junctional complexes, such as tight junctions (TJs), the mechanisms by which SaVs hijack TJs and their proteins for successful entry and infection remain largely unknown. Here, we demonstrate that porcine SaVs (PSaVs) induce early dissociation of TJs, allowing them to bind to the TJ protein occludin as a functional coreceptor. PSaVs then travel in a complex with occludin into late endosomes through Rab5- and Rab7-dependent trafficking. Claudin-1, another TJ protein, does not directly interact with PSaV but facilitates the entry of PSaV into cells as an entry factor. This work contributes to our understanding of the entry of SaV and other caliciviruses into cells and may aid in the development of efficient and affordable drugs to treat SaV infections.",2019 Feb 5,"['Alfajaro, Mia Madel', 'Cho, Eun-Hyo', 'Kim, Deok-Song', 'Kim, Ji-Yun', 'Park, Jun-Gyu', 'Soliman, Mahmoud', 'Baek, Yeong-Bin', 'Park, Chul-Ho', 'Kang, Mun-Il', 'Park, Sang-Ik', 'Cho, Kyoung-Oh']",J Virol,,,True
60f1445b5e867f960e1a6cd99db51a965a2e9006,PMC,Precision public health to inhibit the contagion of disease and move toward a future in which microbes spread health,http://dx.doi.org/10.1186/s12879-019-3715-y,PMC6364421,30727964,CC BY,"Antimicrobial resistance continues to outpace the development of new chemotherapeutics. Novel pathogens continue to evolve and emerge. Public health innovation has the potential to open a new front in the war of “our wits against their genes” (Joshua Lederberg). Dense sampling coupled to next generation sequencing can increase the spatial and temporal resolution of microbial characterization while sensor technologies precisely map physical parameters relevant to microbial survival and spread. Microbial, physical, and epidemiological big data could be combined to improve prospective risk identification. However, applied in the wrong way, these approaches may not realize their maximum potential benefits and could even do harm. Minimizing microbial-human interactions would be a mistake. There is evidence that microbes previously thought of at best “benign” may actually enhance human health. Benign and health-promoting microbiomes may, or may not, spread via mechanisms similar to pathogens. Infectious vaccines are approaching readiness to make enhanced contributions to herd immunity. The rigorously defined nature of infectious vaccines contrasts with indigenous “benign or health-promoting microbiomes” but they may converge. A “microbial Neolithic revolution” is a possible future in which human microbial-associations are understood and managed analogously to the macro-agriculture of plants and animals. Tradeoffs need to be framed in order to understand health-promoting potentials of benign, and/or health-promoting microbiomes and infectious vaccines while also discouraging pathogens. Super-spreaders are currently defined as individuals who play an outsized role in the contagion of infectious disease. A key unanswered question is whether the super-spreader concept may apply similarly to health-promoting microbes. The complex interactions of individual rights, community health, pathogen contagion, the spread of benign, and of health-promoting microbiomes including infectious vaccines require study. Advancing the detailed understanding of heterogeneity in microbial spread is very likely to yield important insights relevant to public health.",2019 Feb 6,"['Thaler, David S.', 'Head, Michael G.', 'Horsley, Andrew']",BMC Infect Dis,,,True
4c874a97c374c6cd2375e7c5f0f690ee911dc3dd,PMC,A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918–1919,http://dx.doi.org/10.1186/s12879-019-3750-8,PMC6364422,30727970,CC BY,"BACKGROUND: In the spring of 1918, the “War to End All Wars”, which would ultimately claim more than 37 million lives, had entered into its final year and would change the global political and economic landscape forever. At the same time, a new global threat was emerging and would become one of the most devastating global health crises in recorded history. MAIN TEXT: The 1918 H1N1 pandemic virus spread across Europe, North America, and Asia over a 12-month period resulting in an estimated 500 million infections and 50–100 million deaths worldwide, of which ~ 50% of these occurred within the fall of 1918 (Emerg Infect Dis 12:15-22, 2006, Bull Hist Med 76:105-115, 2002). However, the molecular factors that contributed to the emergence of, and subsequent public health catastrophe associated with, the 1918 pandemic virus remained largely unknown until 2005, when the characterization of the reconstructed pandemic virus was announced heralding a new era of advanced molecular investigations (Science 310:77-80, 2005). In the century following the emergence of the 1918 pandemic virus we have landed on the Moon, developed the electronic computer (and a global internet), and have eradicated smallpox. In contrast, we have a largely remedial knowledge and understanding of one of the greatest scourges in recorded history. CONCLUSION: Here, we reflect on the 1918 influenza pandemic, including its emergence and subsequent rapid global spread. In addition, we discuss the pathophysiology associated with the 1918 virus and its predilection for the young and healthy, the rise of influenza therapeutic research following the pandemic, and, finally, our level of preparedness for future pandemics.",2019 Feb 6,"['Nickol, Michaela E.', 'Kindrachuk, Jason']",BMC Infect Dis,,,True
ac02f40071a3fc513d2d834ec0bdb3ce8dd16b51,PMC,Estimation in emerging epidemics: biases and remedies,http://dx.doi.org/10.1098/rsif.2018.0670,PMC6364646,30958162,CC BY,"When analysing new emerging infectious disease outbreaks, one typically has observational data over a limited period of time and several parameters to estimate, such as growth rate, the basic reproduction number R(0), the case fatality rate and distributions of serial intervals, generation times, latency and incubation times and times between onset of symptoms, notification, death and recovery/discharge. These parameters form the basis for predicting a future outbreak, planning preventive measures and monitoring the progress of the disease outbreak. We study inference problems during the emerging phase of an outbreak, and point out potential sources of bias, with emphasis on: contact tracing backwards in time, replacing generation times by serial intervals, multiple potential infectors and censoring effects amplified by exponential growth. These biases directly affect the estimation of, for example, the generation time distribution and the case fatality rate, but can then propagate to other estimates such as R(0) and growth rate. We propose methods to remove or at least reduce bias using statistical modelling. We illustrate the theory by numerical examples and simulations.",2019 Jan 16,"['Britton, Tom', 'Scalia Tomba, Gianpaolo']",J R Soc Interface,,,True
deedf1e06ab3cae049c5326cab4e4a2771f54233,PMC,Estimation in emerging epidemics: biases and remedies,http://dx.doi.org/10.1098/rsif.2018.0670,PMC6364646,30958162,CC BY,"When analysing new emerging infectious disease outbreaks, one typically has observational data over a limited period of time and several parameters to estimate, such as growth rate, the basic reproduction number R(0), the case fatality rate and distributions of serial intervals, generation times, latency and incubation times and times between onset of symptoms, notification, death and recovery/discharge. These parameters form the basis for predicting a future outbreak, planning preventive measures and monitoring the progress of the disease outbreak. We study inference problems during the emerging phase of an outbreak, and point out potential sources of bias, with emphasis on: contact tracing backwards in time, replacing generation times by serial intervals, multiple potential infectors and censoring effects amplified by exponential growth. These biases directly affect the estimation of, for example, the generation time distribution and the case fatality rate, but can then propagate to other estimates such as R(0) and growth rate. We propose methods to remove or at least reduce bias using statistical modelling. We illustrate the theory by numerical examples and simulations.",2019 Jan 16,"['Britton, Tom', 'Scalia Tomba, Gianpaolo']",J R Soc Interface,,,True
3ddc728885c89c86d141cc470752c9b740894e53,PMC,The double burden of diabetes and global infection in low and middle-income countries,http://dx.doi.org/10.1093/trstmh/try124,PMC6364794,30517697,CC BY,"Four out of five people in the world with diabetes now live in low- and middle-income countries (LMIC), and the incidence of diabetes is accelerating in poorer communities. Diabetes increases susceptibility to infection and worsens outcomes for some of the world’s major infectious diseases such as tuberculosis, melioidosis and dengue, but the relationship between diabetes and many neglected tropical diseases is yet to be accurately characterised. There is some evidence that chronic viral infections such as hepatitis B and HIV may predispose to the development of type 2 diabetes by chronic inflammatory and immunometabolic mechanisms. Helminth infections such as schistosomiasis may be protective against the development of diabetes, and this finding opens up new territory for discovery of novel therapeutics for the prevention and treatment of diabetes. A greater understanding of the impact of diabetes on risks and outcomes for infections causing significant diseases in LMIC is essential in order to develop vaccines and therapies for the growing number of people with diabetes at risk of infection, and to prioritise research agendas, public health interventions and policy. This review seeks to give an overview of the current international diabetes burden, the evidence for interactions between diabetes and infection, immune mechanisms for the interaction, and potential interventions to tackle the dual burden of diabetes and infection.",2019 Feb 4,"['Dunachie, Susanna', 'Chamnan, Parinya']",Trans R Soc Trop Med Hyg,,,True
c0120b34fddaa312eed6bdbb706c233bd0d0794f,PMC,Theoretical conditions for the coexistence of viral strains with differences in phenotypic traits: a bifurcation analysis,http://dx.doi.org/10.1098/rsos.181179,PMC6366233,30800366,CC BY,"We investigate the dynamics of a wild-type viral strain which generates mutant strains differing in phenotypic properties for infectivity, virulence and mutation rates. We study, by means of a mathematical model and bifurcation analysis, conditions under which the wild-type and mutant viruses, which compete for the same host cells, can coexist. The coexistence conditions are formulated in terms of the basic reproductive numbers of the strains, a maximum value of the mutation rate and the virulence of the pathogens. The analysis reveals that parameter space can be divided into five regions, each with distinct dynamics, that are organized around degenerate Bogdanov–Takens and zero-Hopf bifurcations, the latter of which gives rise to a curve of transcritical bifurcations of periodic orbits. These results provide new insights into the conditions by which viral populations may contain multiple coexisting strains in a stable manner.",2019 Jan 9,"['Nurtay, Anel', 'Hennessy, Matthew G.', 'Sardanyés, Josep', 'Alsedà, Lluís', 'Elena, Santiago F.']",R Soc Open Sci,,,True
a5a3e3edfad63f20fc48ba5885fb9cc863411d2e,PMC,Protective immunity by an engineered DNA vaccine for Mayaro virus,http://dx.doi.org/10.1371/journal.pntd.0007042,PMC6366747,30730897,CC BY,"Mayaro virus (MAYV) of the genus alphavirus is a mosquito-transmitted emerging infectious disease that causes an acute febrile illness, rash, headaches, and nausea that may turn into incapacitating, persistent arthralgias in some victims. Since its discovery in Trinidad in 1954, cases of MAYV infection have largely been confined there and to the northern countries of South America, but recently, MAYV cases have been reported in some island nations in the Caribbean Sea. Accompanying these reports is evidence that new vectors, including Aedes spp. mosquitos, recently implicated in the global spread of Zika and chikungunya viruses, are competent for MAYV transmission, which, if true, could facilitate the spread of MAYV beyond its current range. Despite its status as an emerging virus, there are no licensed vaccines to prevent MAYV infection nor therapeutics to treat it. Here, we describe the development and testing of a novel DNA vaccine, scMAYV-E, that encodes a synthetically-designed consensus MAYV envelope sequence. In vivo electroporation-enhanced immunization of mice with this vaccine induced potent humoral responses including neutralizing antibodies as well as robust T-cell responses to multiple epitopes in the MAYV envelope. Importantly, these scMAYV-E-induced immune responses protected susceptible mice from morbidity and mortality following a MAYV challenge.",2019 Feb 7,"['Choi, Hyeree', 'Kudchodkar, Sagar B.', 'Reuschel, Emma L.', 'Asija, Kanika', 'Borole, Piyush', 'Ho, Michelle', 'Wojtak, Krzysztof', 'Reed, Charles', 'Ramos, Stephanie', 'Bopp, Nathen E.', 'Aguilar, Patricia V.', 'Weaver, Scott C.', 'Kim, J. Joseph', 'Humeau, Laurent', 'Tebas, Pablo', 'Weiner, David B.', 'Muthumani, Kar']",PLoS Negl Trop Dis,,,True
1460431a11ae554624fded17f039eacbda52effb,PMC,Characterisation of N-glycans in the epithelial-like tissue of the rat cochlea,http://dx.doi.org/10.1038/s41598-018-38079-0,PMC6367448,30733536,CC BY,"Membrane proteins (such as ion channels, transporters, and receptors) and secreted proteins are essential for cellular activities. N-linked glycosylation is involved in stability and function of these proteins and occurs at Asn residues. In several organs, profiles of N-glycans have been determined by comprehensive analyses. Nevertheless, the cochlea of the mammalian inner ear, a tiny organ mediating hearing, has yet to be examined. Here, we focused on the stria vascularis, an epithelial-like tissue in the cochlea, and characterised N-glycans by liquid chromatography with mass spectrometry. This hypervascular tissue not only expresses several ion transporters and channels to control the electrochemical balance in the cochlea but also harbours different transporters and receptors that maintain structure and activity of the organ. Seventy-nine N-linked glycans were identified in the rat stria vascularis. Among these, in 55 glycans, the complete structures were determined; in the other 24 species, partial glycosidic linkage patterns and full profiles of the monosaccharide composition were identified. In the process of characterisation, several sialylated glycans were subjected sequentially to two different alkylamidation reactions; this derivatisation helped to distinguish α2,3-linkage and α2,6-linkage sialyl isomers with mass spectrometry. These data should accelerate elucidation of the molecular architecture of the cochlea.",2019 Feb 7,"['Nonomura, Yoriko', 'Sawamura, Seishiro', 'Hanzawa, Ken', 'Nishikaze, Takashi', 'Sekiya, Sadanori', 'Higuchi, Taiga', 'Nin, Fumiaki', 'Uetsuka, Satoru', 'Inohara, Hidenori', 'Okuda, Shujiro', 'Miyoshi, Eiji', 'Horii, Arata', 'Takahashi, Sugata', 'Natsuka, Shunji', 'Hibino, Hiroshi']",Sci Rep,,,True
575ce9765e914a2bdb2a02b265905f9e7e781c67,PMC,Characterisation of N-glycans in the epithelial-like tissue of the rat cochlea,http://dx.doi.org/10.1038/s41598-018-38079-0,PMC6367448,30733536,CC BY,"Membrane proteins (such as ion channels, transporters, and receptors) and secreted proteins are essential for cellular activities. N-linked glycosylation is involved in stability and function of these proteins and occurs at Asn residues. In several organs, profiles of N-glycans have been determined by comprehensive analyses. Nevertheless, the cochlea of the mammalian inner ear, a tiny organ mediating hearing, has yet to be examined. Here, we focused on the stria vascularis, an epithelial-like tissue in the cochlea, and characterised N-glycans by liquid chromatography with mass spectrometry. This hypervascular tissue not only expresses several ion transporters and channels to control the electrochemical balance in the cochlea but also harbours different transporters and receptors that maintain structure and activity of the organ. Seventy-nine N-linked glycans were identified in the rat stria vascularis. Among these, in 55 glycans, the complete structures were determined; in the other 24 species, partial glycosidic linkage patterns and full profiles of the monosaccharide composition were identified. In the process of characterisation, several sialylated glycans were subjected sequentially to two different alkylamidation reactions; this derivatisation helped to distinguish α2,3-linkage and α2,6-linkage sialyl isomers with mass spectrometry. These data should accelerate elucidation of the molecular architecture of the cochlea.",2019 Feb 7,"['Nonomura, Yoriko', 'Sawamura, Seishiro', 'Hanzawa, Ken', 'Nishikaze, Takashi', 'Sekiya, Sadanori', 'Higuchi, Taiga', 'Nin, Fumiaki', 'Uetsuka, Satoru', 'Inohara, Hidenori', 'Okuda, Shujiro', 'Miyoshi, Eiji', 'Horii, Arata', 'Takahashi, Sugata', 'Natsuka, Shunji', 'Hibino, Hiroshi']",Sci Rep,,,True
273ed1bf60b19e3db4ab3894a20598336b7e0ef4,PMC,Effect of prebiotic supplementation with stabilized rice bran in milk of pre-weaned organic Holstein calves,http://dx.doi.org/10.1186/s12917-019-1802-3,PMC6367819,30732598,CC BY,"BACKGROUND: The first month of life possess significant challenges for dairy calves due to high susceptibility to digestive diseases. The objective of this study was to evaluate the effect of prebiotic supplementation with stabilized rice bran (SRB) in milk on health, immunity, and performance of pre-weaned organic dairy calves. Holstein heifer calves (n = 90) were enrolled at 6 ± 1 days old and monitored for 28 days, from July to August 2017. Calves were randomly assigned to a control (CTR; n = 45) or a treatment group (SRB; n = 45). The CTR group received milk alone and the SRB group received 120 g of SRB per day in milk to achieve a 10% w/w dose of the total calories. Daily health evaluations were conducted to score health status and disease severity (healthy, slightly affected, moderately or severely sick) of calves, through integrated assessment of diarrhea, dehydration, attitude, and milk intake. Body weights and fecal IgA quantification were completed on the first and last day of the study. RESULTS: Overall, weight gain and fecal IgA concentrations were not affected by the dietary addition of SRB. The total number of calf-days classified as healthy or sick were not different between treatment groups. Similarly, the number of calf-days categorized as slightly affected, moderately sick, or severely sick did not differ between treatment groups. Time to event analyses indicated a tendency for a treatment effect in the time to the first moderate case of diarrhea (P = 0.08), as well as in the time to recovery from diarrhea (P = 0.052), favoring control calves. CONCLUSIONS: These results indicated that the dietary addition of SRB in milk did not have an effect in health, immunity or performance of pre-weaned dairy calves.",2019 Feb 7,"['Velasquez-Munoz, Ana', 'Manriquez, Diego', 'Paudyal, Sushil', 'Han, Hyungchul', 'Callan, Robert', 'Ryan, Elizabeth P.', 'Pinedo, Pablo']",BMC Vet Res,,,True
488cfd5c8020cb081650f65c3cf7646ab9079654,PMC,First Complete Genome Sequence of Human Coronavirus HKU1 from a Nonill Bat Guano Miner in Thailand,http://dx.doi.org/10.1128/MRA.01457-18,PMC6368654,30746519,CC BY,"Human coronavirus HKU1 (HCoV-HKU1) was first detected in a patient with viral pneumonia from Hong Kong in 2004. Here, we report the first complete genome sequence of HCoV-HKU1 from Thailand, obtained from a nonill person who worked in a bat cave. Phylogenetic tree analysis revealed it as a group B HCoV-HKU1.",2019 Feb 7,"['Joyjinda, Yutthana', 'Rodpan, Apaporn', 'Chartpituck, Pongtorn', 'Suthum, Krairerk', 'Yaemsakul, Suphaluk', 'Cheun-Arom, Thaniwan', 'Bunprakob, Saowalak', 'Olival, Kevin J.', 'Stokes, Martha M.', 'Hemachudha, Thiravat', 'Wacharapluesadee, Supaporn']",Microbiol Resour Announc,,,True
52a8c303b6e299b80b20975105e7c9852beec5c6,PMC,Single stranded (ss)RNA-mediated antiviral response against infectious laryngotracheitis virus infection,http://dx.doi.org/10.1186/s12866-019-1398-6,PMC6368756,30736730,CC BY,"BACKGROUND: Single stranded ribonucleic acid (ssRNA) binds to toll-like receptor (TLR)7 leading to recruitment of immune cells and production of pro-inflammatory cytokines, which has been shown in mammals. In chickens, synthetic ssRNA analog, resiquimod, has been shown to elicit antiviral response against infectious bursal disease virus infection. The objective of this study was to determine the innate host responses activated by the pre-hatch in ovo administration of resiquimod against infectious laryngotracheitis virus (ILTV) infection in chickens post-hatch. RESULTS: First, we observed that in ovo treatment of resiquimod at embryo day (ED) 18 increases macrophage recruitment in respiratory and gastrointestinal tissues of chicken day 1 post-hatch in addition to interleukin (IL)-1β in lungs. Second, we observed that in ovo treatment of resiquimod reduces ILTV cloacal shedding at 7 days post-infection (dpi) when challenged at day 1 post-hatch coinciding with higher macrophage recruitment. In vitro, we found that resiquimod enhances production of nitric oxide (NO) and IL-1β and not type 1 interferon (IFN) activity in avian macrophages. Although, the antiviral response against ILTV is associated with the enhanced innate immune response, it is not dependent on any of the innate immune mediators observed as has been shown in vitro using avian macrophage. CONCLUSION: This study provides insights into the mechanisms of antiviral response mediated by resiquimod, particularly against ILTV infection in chicken.",2019 Feb 8,"['Abdul-Cader, Mohamed Sarjoon', 'De Silva Senapathi, Upasama', 'Ahmed-Hassan, Hanaa', 'Sharif, Shayan', 'Abdul-Careem, Mohamed Faizal']",BMC Microbiol,,,True
83bee2f8fff1d0da5230174abcd935d8b1113665,PMC,Vaccine Development for Nipah Virus Infection in Pigs,http://dx.doi.org/10.3389/fvets.2019.00016,PMC6369168,30778392,CC BY,"Nipah virus (NiV) causes a severe and often fatal neurological disease in humans. Whilst fruit bats are considered the natural reservoir, NiV also infects pigs and may cause an unapparent or mild disease. Direct pig-to-human transmission was responsible for the first and still most devastating NiV outbreaks in Malaysia and Singapore in 1998–99, with nearly 300 human cases and over 100 fatalities. Pigs can therefore play a key role in the epidemiology of NiV by acting as an “amplifying” host. The outbreak in Singapore ended with the prohibition of pig imports from Malaysia and the Malaysian outbreak was ended by culling 45% of the country's pig population with costs exceeding US$500 million. Despite the importance of NiV as an emerging disease with the potential for pandemic, no vaccines, or therapeutics are currently approved for human or livestock use. In this mini-review, we will discuss current knowledge of NiV infection in pigs; our ongoing work to develop a NiV vaccine for use in pigs; and the pig as a model to support human vaccine development.",2019 Feb 4,"['McLean, Rebecca K.', 'Graham, Simon P.']",Front Vet Sci,,,True
10f63acdd41437902fb627803c57d57dec2c4716,PMC,"Prevalence and genetic diversity of coronaviruses in wild birds, Finland",http://dx.doi.org/10.1080/20008686.2017.1408360,PMC6369310,30788065,CC BY,"Introduction: Migratory birds act as hosts for a number of zoonotic viruses, and have the ability to disperse these viruses to distant geographic locations. Coronaviruses (CoVs) represent a family of zoonotic viruses with wide variety of animal hosts, including birds and humans. The infections caused by coronaviruses vary from mild to severe, depending on the viral species and the host. Since the coronaviruses exhibit extraordinary large RNA genome, also the rate of homologous recombination is high, which in turn contributes to the genetic diversity and interspecies host-switches of CoVs. The emergence of novel CoVs has been rich during the last decades, and wild birds seem to serve as reservoirs for a variety of CoV strains. We examined the CoVs circulating among wild birds in Finland. Materials and methods: Samples (cloacal swab, tracheal swab, oropharyngeal swab, or tissue) representing 61 bird species were collected during 2010-2013, and examined by RT-PCR targeting the RdRp gene for the presence of CoV RNA. Results: Altogether 51/939 (5.4%) of the examined birds were found positive by RT-PCR. Diverse gamma- and deltacoronavirus sequences were detected. Discussion: Gamma- and deltacoronaviruses circulate among wild birds in Finland. The number of CoV-positive birds detected each year varies greatly.",2017 Nov 28,"['Hepojoki, Satu', 'Lindh, Erika', 'Vapalahti, Olli', 'Huovilainen, Anita']",Infect Ecol Epidemiol,,,True
c5dd9137d5d43d4d46606a219f3ecce6d22375c4,PMC,Investing in Public Health Microbiology Laboratories in Western Balkan Countries Enhances Health Security From Communicable Disease Threats in Europe,http://dx.doi.org/10.3389/fpubh.2019.00008,PMC6369834,30778382,CC BY,"The European Centre for Disease Prevention and Control (ECDC), under the EU enlargement policy, has supported national efforts of Western Balkan countries to strengthen their communicable disease prevention and control systems. The new EU strategy “A credible enlargement perspective for and enhanced EU engagement with the Western Balkans” advocates transformation processes that will build the foundation of EU-oriented national reforms. Well-functioning public health microbiology laboratories are key for early detection and control of infectious diseases, and thus maintaining and enhancing health security in Europe. In order to help Western Balkan countries to improve their national capacities, ECDC facilitated needs assessments and identified key areas for advancement toward effective public health microbiology systems. Countries identified gaps in their laboratory data reporting and exchange systems. Harmonized and effective procedures for handling of highly contagious agents and cross-border transportation of biological samples were often lacking, as well as the systematic use of diagnostic testing at the primary care level or referral of patients, in particular for detection of antimicrobial resistance. There is a clear need to address the financial investment required for sustaining sufficient numbers of skilled laboratory workforce, laboratory supplies, and the development of new methods and techniques, including investment in emerging laboratory technologies, such as molecular typing by whole genome sequencing. This article highlights the key areas for investing in public health microbiology laboratories in Western Balkan countries needed to strengthen health security in Europe.",2019 Feb 4,"['Bajoriniene, Agne', 'Leitmeyer, Katrin C.', 'Struelens, Marc J.', 'Kokki, Maarit H.', None]",Front Public Health,,,True
5811a8c7d5d59061c11b2084dca1e307c49867b7,PMC,"Features and drivers for energy-related carbon emissions in mega city: The case of Guangzhou, China based on an extended LMDI model",http://dx.doi.org/10.1371/journal.pone.0210430,PMC6370191,30742627,CC BY,"Based on the apparent energy consumption data, a systematic and comprehensive city-level total carbon accounting approach was established and applied in Guangzhou, China. A newly extended LMDI method based on the Kaya identity was adopted to examine the main drivers for the carbon emissions increments both at the industrial sector and the residential sector. Research results are listed as follow: (1) Carbon emissions embodied in the imported electricity played a significant important role in emissions mitigation in Guangzhou. (2) The influences and impacts of various driving factors on industrial and residential carbon emissions are different in the three different development periods, namely, the 10(th) five-year plan period (2003–2005), the 11(th) five-year plan period (2005–2010), and the 12(th) five-year plan period (2010–2013). The main reasons underlying these influencing mechanisms were different policy measures announced by the central and local government during the different five-year plan periods. (3) The affluence effect (g-effect) was the dominant positive effect in driving emissions increase, while the energy intensity effect of production (e-effect-Production), the economic structure effect (s-effect) and the carbon intensity effect of production (f-effect-Production) were the main contributing factors suppressing emissions growth at the industrial sector. (4) The affluence effect of urban (g-effect-AUI) was the most dominant positive driving factor on emissions increment, while the energy intensity effect of urban (e-effect-Urban) played the most important role in curbing emissions growth at the residential sector.",2019 Feb 11,"['Wang, Changjian', 'Wu, Kangmin', 'Zhang, Xinlin', 'Wang, Fei', 'Zhang, Hongou', 'Ye, Yuyao', 'Wu, Qitao', 'Huang, Gengzhi', 'Wang, Yang', 'Wen, Bin']",PLoS One,,,True
49d38b24e73f9fc1e483f13ca5b9cbfc298fcd95,PMC,Cdrom Archive: A Gateway to Study Camel Phenotypes,http://dx.doi.org/10.3389/fgene.2019.00048,PMC6370635,30804986,CC BY,"Camels are livestock that exhibit unique morphological, biochemical, and behavioral traits, which arose by natural and artificial selection. Investigating the molecular basis of camel traits has been limited by: (1) the absence of a comprehensive record of morphological trait variation (e.g., diseases) and the associated mode of inheritance, (2) the lack of extended pedigrees of specific trait(s), and (3) the long reproductive cycle of the camel, which makes the cost of establishing and maintaining a breeding colony (i.e., monitoring crosses) prohibitively high. Overcoming these challenges requires (1) detailed documentation of phenotypes/genetic diseases and their likely mode of inheritance (and collection of related DNA samples), (2) conducting association studies to identify phenotypes/genetic diseases causing genetic variants (instead of classical linkage analysis, which requires extended pedigrees), and (3) validating likely causative variants by screening a large number of camel samples from different populations. We attempt to address these issues by establishing a systematic way of collecting camel DNA samples, and associated phenotypic information, which we call the “Cdrom Archive.” Here, we outline the process of building this archive to introduce it to other camel researchers (as an example). Additionally, we discuss the use of this archive to study the phenotypic traits of Arabian Peninsula camel breeds (the “Mezayen” camels). Using the Cdrom Archive, we report variable phenotypic traits related to the coat (color, length, and texture), ear and tail lengths, along with other morphological measurements.",2019 Feb 5,"['Alhaddad, Hasan', 'Alhajeri, Bader H.']",Front Genet,,,True
e639223272807d9187847fb3a70c6026cb890d37,PMC,The PD-1/PD-L1 Pathway Affects the Expansion and Function of Cytotoxic CD8(+) T Cells During an Acute Retroviral Infection,http://dx.doi.org/10.3389/fimmu.2019.00054,PMC6370637,30804928,CC BY,"Cytotoxic CD8(+) T lymphocytes (CTL) efficiently control acute virus infections but can become exhausted when a chronic infection develops. The checkpoint receptor PD-1 suppresses the functionality of virus-specific CD8(+) T cells during chronic infection. However, the role of the PD-L1/PD-1 pathway during the acute phase of infections has not been well characterized. In the current study the effects of PD-1 or PD-L1 deficiency on the CD8(+) T cell response against Friend retroviral (FV) infection of knockout mice was analyzed during acute infection. We observed an enhanced proliferation, functional maturation, and reduced apoptosis of effector CD8(+) T cells in the absence of PD-1 or PD-L1. The knockout of PD-L1 had a stronger effect on the functionality of CD8(+) T cells than that of PD-1. Augmented CTL responses were associated with an improved control of FV replication. The strong phenotype of FV-infected PD-L1 knockout mice was independent of the interaction with CD80 as an additional receptor for PD-L1. Furthermore, we performed a detailed analysis of the production of different granzymes in virus-specific CD8(+) T cells and observed that especially the simultaneous production of multiple granzymes in individual T cells (multifunctionality) was under the control of the PD-1/PD-L1 pathway. The findings from this study allow for a better understanding of the development of antiviral cytotoxic immunity during acute viral infections.",2019 Feb 5,"['David, Paul', 'Megger, Dominik A.', 'Kaiser, Tamara', 'Werner, Tanja', 'Liu, Jia', 'Chen, Lieping', 'Sitek, Barbara', 'Dittmer, Ulf', 'Zelinskyy, Gennadiy']",Front Immunol,,,True
d9c174a11b8d2bd0a4df65b17e576934f3cce31c,PMC,Development of a recombinant Newcastle disease virus-vectored vaccine for infectious bronchitis virus variant strains circulating in Egypt,http://dx.doi.org/10.1186/s13567-019-0631-5,PMC6371441,30744668,CC BY,"Infectious bronchitis virus (IBV) causes a major disease problem for the poultry industry worldwide. The currently used live-attenuated vaccines have the tendency to mutate and/or recombine with circulating field strains resulting in the emergence of vaccine-derived variant viruses. In order to circumvent these issues, and to develop a vaccine that is more relevant to Egypt and its neighboring countries, a recombinant avirulent Newcastle disease virus (rNDV) strain LaSota was constructed to express the codon-optimized S glycoprotein of the Egyptian IBV variant strain IBV/Ck/EG/CU/4/2014 belonging to GI-23 lineage, that is prevalent in Egypt and in the Middle East. A wild type and two modified versions of the IBV S protein were expressed individually by rNDV. A high level of S protein expression was detected in vitro by Western blot and immunofluorescence analyses. All rNDV-vectored IBV vaccine candidates were genetically stable, slightly attenuated and showed growth patterns comparable to that of parental rLaSota virus. Single-dose vaccination of 1-day-old SPF White Leghorn chicks with the rNDVs expressing IBV S protein provided significant protection against clinical disease after IBV challenge but did not show reduction in tracheal viral shedding. Single-dose vaccination also provided complete protection against virulent NDV challenge. However, prime-boost vaccination using rNDV expressing the wild type IBV S protein provided better protection, after IBV challenge, against clinical signs and significantly reduced tracheal viral shedding. These results indicate that the NDV-vectored IBV vaccines are promising bivalent vaccine candidates to control both infectious bronchitis and Newcastle disease in Egypt. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13567-019-0631-5) contains supplementary material, which is available to authorized users.",2019 Feb 11,"['Abozeid, Hassanein H.', 'Paldurai, Anandan', 'Varghese, Berin P.', 'Khattar, Sunil K.', 'Afifi, Manal A.', 'Zouelfakkar, Sahar', 'El-Deeb, Ayman H.', 'El-Kady, Magdy F.', 'Samal, Siba K.']",Vet Res,,,True
7e9a78b8f365405455eb60c2645de7bd7359e7a1,PMC,Pathogen diversity drives the evolution of generalist MHC-II alleles in human populations,http://dx.doi.org/10.1371/journal.pbio.3000131,PMC6372212,30703088,CC BY,"Central players of the adaptive immune system are the groups of proteins encoded in the major histocompatibility complex (MHC), which shape the immune response against pathogens and tolerance to self-peptides. The corresponding genomic region is of particular interest, as it harbors more disease associations than any other region in the human genome, including associations with infectious diseases, autoimmune disorders, cancers, and neuropsychiatric diseases. Certain MHC molecules can bind to a much wider range of epitopes than others, but the functional implication of such an elevated epitope-binding repertoire has remained largely unclear. It has been suggested that by recognizing more peptide segments, such promiscuous MHC molecules promote immune response against a broader range of pathogens. If so, the geographical distribution of MHC promiscuity level should be shaped by pathogen diversity. Three lines of evidence support the hypothesis. First, we found that in pathogen-rich geographical regions, humans are more likely to carry highly promiscuous MHC class II DRB1 alleles. Second, the switch between specialist and generalist antigen presentation has occurred repeatedly and in a rapid manner during human evolution. Third, molecular positions that define promiscuity level of MHC class II molecules are especially diverse and are under positive selection in human populations. Taken together, our work indicates that pathogen load maintains generalist adaptive immune recognition, with implications for medical genetics and epidemiology.",2019 Jan 31,"['Manczinger, Máté', 'Boross, Gábor', 'Kemény, Lajos', 'Müller, Viktor', 'Lenz, Tobias L.', 'Papp, Balázs', 'Pál, Csaba']",PLoS Biol,,,True
7ec36d372303be7d61deb6a7ef724495a6d90614,PMC,Determination of host proteins composing the microenvironment of coronavirus replicase complexes by proximity-labeling,http://dx.doi.org/10.7554/eLife.42037,PMC6372286,30632963,CC BY,"Positive-sense RNA viruses hijack intracellular membranes that provide niches for viral RNA synthesis and a platform for interactions with host proteins. However, little is known about host factors at the interface between replicase complexes and the host cytoplasm. We engineered a biotin ligase into a coronaviral replication/transcription complex (RTC) and identified >500 host proteins constituting the RTC microenvironment. siRNA-silencing of each RTC-proximal host factor demonstrated importance of vesicular trafficking pathways, ubiquitin-dependent and autophagy-related processes, and translation initiation factors. Notably, detection of translation initiation factors at the RTC was instrumental to visualize and demonstrate active translation proximal to replication complexes of several coronaviruses. Collectively, we establish a spatial link between viral RNA synthesis and diverse host factors of unprecedented breadth. Our data may serve as a paradigm for other positive-strand RNA viruses and provide a starting point for a comprehensive analysis of critical virus-host interactions that represent targets for therapeutic intervention.",,"[""V'kovski, Philip"", 'Gerber, Markus', 'Kelly, Jenna', 'Pfaender, Stephanie', 'Ebert, Nadine', 'Braga Lagache, Sophie', 'Simillion, Cedric', 'Portmann, Jasmine', 'Stalder, Hanspeter', 'Gaschen, Véronique', 'Bruggmann, Rémy', 'Stoffel, Michael H', 'Heller, Manfred', 'Dijkman, Ronald', 'Thiel, Volker']",eLife.; 8:e42037,,,True
179338a972eb486bae25e1898b54441c7534e0b2,PMC,Rapid molecular detection of macrolide resistance,http://dx.doi.org/10.1186/s12879-019-3762-4,PMC6373131,30755177,CC BY,"BACKGROUND: Emerging antimicrobial resistance is a significant threat to human health. However, methods for rapidly diagnosing antimicrobial resistance generally require multi-day culture-based assays. Macrolide efflux gene A, mef(A), provides resistance against erythromycin and azithromycin and is known to be laterally transferred among a wide range of bacterial species. METHODS: We use Recombinase Polymerase Assay (RPA) to detect the antimicrobial resistance gene mef(A) from raw lysates without nucleic acid purification. To validate these results we performed broth dilution assays to assess antimicrobial resistance to erythromycin and ampicillin (a negative control). RESULTS: We validate the detection of mef(A) in raw lysates of Streptococcus pyogenes, S. pneumoniae, S. salivarius, and Enterococcus faecium bacterial lysates within 7–10 min of assay time. We show that detection of mef(A) accurately predicts real antimicrobial resistance assessed by traditional culture methods, and that the assay is robust to high levels of spiked-in non-specific nucleic acid contaminant. The assay was unaffected by single-nucleotide polymorphisms within divergent mef(A) gene sequences, strengthening its utility as a robust diagnostic tool. CONCLUSIONS: This finding opens the door to implementation of rapid genomic diagnostics in a clinical setting, while providing researchers a rapid, cost-effective tool to track antibiotic resistance in both pathogens and commensal strains.",2019 Feb 12,"['Nelson, Megan M.', 'Waldron, Christopher L.', 'Bracht, John R.']",BMC Infect Dis,,,True
8ab85680354ff42be1c0101a4acd9db08a9319d6,PMC,Highly Efficient Transgenesis in Ferrets Using CRISPR/Cas9-Mediated Homology-Independent Insertion at the ROSA26 Locus,http://dx.doi.org/10.1038/s41598-018-37192-4,PMC6374392,30760763,CC BY,"The domestic ferret (Mustela putorius furo) has proven to be a useful species for modeling human genetic and infectious diseases of the lung and brain. However, biomedical research in ferrets has been hindered by the lack of rapid and cost-effective methods for genome engineering. Here, we utilized CRISPR/Cas9-mediated, homology-independent insertion at the ROSA26 “safe harbor” locus in ferret zygotes and created transgenic animals expressing a dual-fluorescent Cre-reporter system flanked by PhiC31 and Bxb1 integrase attP sites. Out of 151 zygotes injected with circular transgene-containing plasmid and Cas9 protein loaded with the ROSA26 intron-1 sgRNA, there were 23 births of which 5 had targeted integration events (22% efficiency). The encoded tdTomato transgene was highly expressed in all tissues evaluated. Targeted integration was verified by PCR analyses, Southern blot, and germ-line transmission. Function of the ROSA26-CAG-(LoxP)tdTomato(StopLoxP)EGFP (ROSA-TG) Cre-reporter was confirmed in primary cells following Cre expression. The Phi31 and Bxb1 integrase attP sites flanking the transgene will also enable rapid directional insertion of any transgene without a size limitation at the ROSA26 locus. These methods and the model generated will greatly enhance biomedical research involving lineage tracing, the evaluation of stem cell therapy, and transgenesis in ferret models of human disease.",2019 Feb 13,"['Yu, Miao', 'Sun, Xingshen', 'Tyler, Scott R.', 'Liang, Bo', 'Swatek, Anthony M.', 'Lynch, Thomas J.', 'He, Nan', 'Yuan, Feng', 'Feng, Zehua', 'Rotti, Pavana G.', 'Choi, Soon H.', 'Shahin, Weam', 'Liu, Xiaoming', 'Yan, Ziying', 'Engelhardt, John F.']",Sci Rep,,,False
5009d7b5a27efb9b31d50a5266d077c4313c295a,PMC,Highly Efficient Transgenesis in Ferrets Using CRISPR/Cas9-Mediated Homology-Independent Insertion at the ROSA26 Locus,http://dx.doi.org/10.1038/s41598-018-37192-4,PMC6374392,30760763,CC BY,"The domestic ferret (Mustela putorius furo) has proven to be a useful species for modeling human genetic and infectious diseases of the lung and brain. However, biomedical research in ferrets has been hindered by the lack of rapid and cost-effective methods for genome engineering. Here, we utilized CRISPR/Cas9-mediated, homology-independent insertion at the ROSA26 “safe harbor” locus in ferret zygotes and created transgenic animals expressing a dual-fluorescent Cre-reporter system flanked by PhiC31 and Bxb1 integrase attP sites. Out of 151 zygotes injected with circular transgene-containing plasmid and Cas9 protein loaded with the ROSA26 intron-1 sgRNA, there were 23 births of which 5 had targeted integration events (22% efficiency). The encoded tdTomato transgene was highly expressed in all tissues evaluated. Targeted integration was verified by PCR analyses, Southern blot, and germ-line transmission. Function of the ROSA26-CAG-(LoxP)tdTomato(StopLoxP)EGFP (ROSA-TG) Cre-reporter was confirmed in primary cells following Cre expression. The Phi31 and Bxb1 integrase attP sites flanking the transgene will also enable rapid directional insertion of any transgene without a size limitation at the ROSA26 locus. These methods and the model generated will greatly enhance biomedical research involving lineage tracing, the evaluation of stem cell therapy, and transgenesis in ferret models of human disease.",2019 Feb 13,"['Yu, Miao', 'Sun, Xingshen', 'Tyler, Scott R.', 'Liang, Bo', 'Swatek, Anthony M.', 'Lynch, Thomas J.', 'He, Nan', 'Yuan, Feng', 'Feng, Zehua', 'Rotti, Pavana G.', 'Choi, Soon H.', 'Shahin, Weam', 'Liu, Xiaoming', 'Yan, Ziying', 'Engelhardt, John F.']",Sci Rep,,,True
7e6a3be51808891b99a73f57faaa454670055e45,PMC,Epidemic Models of Contact Tracing: Systematic Review of Transmission Studies of Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome,http://dx.doi.org/10.1016/j.csbj.2019.01.003,PMC6376160,30809323,CC BY,"The emergence and reemergence of coronavirus epidemics sparked renewed concerns from global epidemiology researchers and public health administrators. Mathematical models that represented how contact tracing and follow-up may control Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) transmissions were developed for evaluating different infection control interventions, estimating likely number of infections as well as facilitating understanding of their likely epidemiology. We reviewed mathematical models for contact tracing and follow-up control measures of SARS and MERS transmission. Model characteristics, epidemiological parameters and intervention parameters used in the mathematical models from seven studies were summarized. A major concern identified in future epidemics is whether public health administrators can collect all the required data for building epidemiological models in a short period of time during the early phase of an outbreak. Also, currently available models do not explicitly model constrained resources. We urge for closed-loop communication between public health administrators and modelling researchers to come up with guidelines to delineate the collection of the required data in the midst of an outbreak and the inclusion of additional logistical details in future similar models.",2019 Jan 26,"['Kwok, Kin On', 'Tang, Arthur', 'Wei, Vivian W.I.', 'Park, Woo Hyun', 'Yeoh, Eng Kiong', 'Riley, Steven']",Comput Struct Biotechnol J,,,False
1d572b31e29c16909825aa14dc9e462020d95303,PMC,Camouflage and interception: how pathogens evade detection by intracellular nucleic acid sensors,http://dx.doi.org/10.1111/imm.13030,PMC6376273,30499584,CC BY,"Intracellular DNA and RNA sensors play a vital part in the innate immune response to viruses and other intracellular pathogens, causing the secretion of type I interferons, cytokines and chemokines from infected cells. Pathogen RNA can be detected by retinoic‐acid inducible gene I‐like receptors in the cytosol, whereas cytosolic DNA is recognized by DNA sensors such as cyclic GMP‐AMP synthase (cGAS). The resulting local immune response, which is initiated within hours of infection, is able to eliminate many pathogens before they are able to establish an infection in the host. For this reason, all viruses, and some intracellular bacteria and protozoa, need to evade detection by nucleic acid sensors. Immune evasion strategies include the sequestration and modification of nucleic acids, and the inhibition or degradation of host factors involved in innate immune signalling. Large DNA viruses, such as herpesviruses, often use multiple viral proteins to inhibit signalling cascades at several different points; for instance herpes simplex virus 1 targets both DNA sensors cGAS and interferon‐γ‐inducible protein 16, as well as the adaptor protein STING (stimulator of interferon genes) and other signalling factors in the pathway. Viruses with a small genome encode only a few immunomodulatory proteins, but these are often multifunctional, such as the NS1 protein from influenza A virus, which inhibits RNA sensing in multiple ways. Intracellular bacteria and protozoa can also be detected by nucleic acid sensors. However, as the type I interferon response is not always beneficial for the host under these circumstances, some bacteria subvert, rather than evade, these signalling cascades for their own gain.",2019 Mar 18,"['Unterholzner, Leonie', 'Almine, Jessica F.']",Immunology,,,True
1363643127b0fd76d3c6b848e07cfc2ed3f75328,PMC,A medium-throughput screen for inhibitors of human metapneumovirus,http://dx.doi.org/10.1177/2040206619830197,PMC6376503,30759993,CC BY,"Human metapneumovirus, a paramyxovirus discovered in 2001, is a major cause of lower respiratory infection in adults and children worldwide. There are no licensed vaccines or drugs for human metapneumovirus. We developed a fluorescent, cell-based medium-throughput screening assay for human metapneumovirus that captures inhibitors of all stages of the viral lifecycle except budding of progeny virus particles from the cell membrane. We optimized and validated the assay and performed a successful medium-throughput screening. A number of hits were identified, several of which were confirmed to inhibit viral replication in secondary assays. This assay offers potential to discover new antivirals for human metapneumovirus and related respiratory viruses. Compounds discovered using the medium-throughput screening may also provide useful probes of viral biology.",2019 Feb 13,"['Becker, Jennifer C', 'Tollefson, Sharon J', 'Weaver, David', 'Williams, John V']",Antivir Chem Chemother,,,True
3d865d38326b36802453ee76933f092b6b7697fc,PMC,A medium-throughput screen for inhibitors of human metapneumovirus,http://dx.doi.org/10.1177/2040206619830197,PMC6376503,30759993,CC BY,"Human metapneumovirus, a paramyxovirus discovered in 2001, is a major cause of lower respiratory infection in adults and children worldwide. There are no licensed vaccines or drugs for human metapneumovirus. We developed a fluorescent, cell-based medium-throughput screening assay for human metapneumovirus that captures inhibitors of all stages of the viral lifecycle except budding of progeny virus particles from the cell membrane. We optimized and validated the assay and performed a successful medium-throughput screening. A number of hits were identified, several of which were confirmed to inhibit viral replication in secondary assays. This assay offers potential to discover new antivirals for human metapneumovirus and related respiratory viruses. Compounds discovered using the medium-throughput screening may also provide useful probes of viral biology.",2019 Feb 13,"['Becker, Jennifer C', 'Tollefson, Sharon J', 'Weaver, David', 'Williams, John V']",Antivir Chem Chemother,,,False
fec800677847384e7ac7f2bc3164762e729360f2,PMC,Comparison of influenza disease burden in older populations of Hong Kong and Brisbane: the impact of influenza and pneumococcal vaccination,http://dx.doi.org/10.1186/s12879-019-3735-7,PMC6376732,30764779,CC BY,"BACKGROUND: Influenza and pneumococcal vaccine uptake in the older population aged 65 years or over of Hong Kong dramatically increased since the 2003 SARS outbreak. This study is aimed to evaluate the impact of increased coverage of influenza and pneumococcal vaccines by comparing the change of disease burden in the older population of Hong Kong, with the burden in the older population of Brisbane with relatively high vaccine coverage in the past fifteen years. METHODS: Time series segmented regression models were applied to weekly numbers of cause-specific mortality or hospitalization of Hong Kong and Brisbane. Annual excess rates of mortality or hospitalization associated with influenza in the older population were estimated for the pre-SARS (reference period), post-SARS and post-pandemic period, respectively. The rate ratios (RRs) between these periods were also calculated to assess the relative change of disease burden. RESULTS: Compared to the pre-SARS period, excess rates of mortality associated with influenza during the post-SARS period in Hong Kong decreased for cardiorespiratory diseases (RR = 0.90, 95% CI 0.80, 1.01), stroke (RR = 0.74, 95% CI 0.50, 1.09), and ischemic heart diseases (RR = 0.45, 95% CI 0.34, 0.58). The corresponding RRs in Brisbane were 0.79 (95% CI 0.54, 1.15), 0.33 (0.13, 0.80), and 1.09 (0.62, 1.90), respectively. Only the mortality of ischemic heart diseases showed a greater reduction in Hong Kong than in Brisbane. During the post-pandemic period, excess rates of all-cause mortality increased in Hong Kong, but to a lesser extent than in Brisbane (RR = 1.41 vs 2.39). CONCLUSION: A relative decrease (or less of an increase) of influenza disease burden was observed in the older population of Hong Kong after increased coverage of influenza and pneumococcal vaccines in this population, as compared to those of Brisbane where vaccination rates remained stable. The lack of significant findings in some disease categories highlights the challenges of evaluating the benefits of vaccination at the population level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-3735-7) contains supplementary material, which is available to authorized users.",2019 Feb 14,"['Yang, Lin', 'Chan, King Pan', 'Wong, Chit Ming', 'Chiu, Susan Shui Seng', 'Magalhaes, Ricardo J. Soares', 'Thach, Thuan Quoc', 'Peiris, Joseph Syrial Malik', 'Clements, Archie C. A.', 'Hu, Wenbiao']",BMC Infect Dis,,,True
60c8d039946e8658aaa9d51d6f95601595262756,PMC,A new prokaryotic expression vector for the expression of antimicrobial peptide abaecin using SUMO fusion tag,http://dx.doi.org/10.1186/s12896-019-0506-x,PMC6377777,30770741,CC BY,"BACKGROUND: Despite the growing demand for antimicrobial peptides (AMPs) for clinical use as an alternative approach against antibiotic-resistant bacteria, the manufacture of AMPs relies on expensive, small-scale chemical methods. The small ubiquitin-related modifier (SUMO) tag is industrially practical for increasing the yield of recombinant proteins by increasing solubility and preventing degradation in expression systems. RESULTS: A new vector system, pKSEC1, was designed to produce AMPs, which can work in prokaryotic systems such as Escherichia coli and plant chloroplasts. 6xHis was tagged to SUMO for purification of SUMO-fused AMPs. Abaecin, a 34-aa-long antimicrobial peptide from honeybees, was expressed in a fusion form to 6xHis-SUMO in a new vector system to evaluate the prokaryotic expression platform of the antimicrobial peptides. The fusion sequences were codon-optimized in three different combinations and expressed in E. coli. The combination of the native SUMO sequence with codon-optimized abaecin showed the highest expression level among the three combinations, and most of the expressed fusion proteins were detected in soluble fractions. Cleavage of the SUMO tag by sumoase produced a 29-aa-long abaecin derivative with a C-terminal deletion. However, this abaecin derivative still retained the binding sequence for its target protein, DnaK. Antibacterial activity of the 29-aa long abaecin was tested against Bacillus subtilis alone or in combination with cecropin B. The combined treatment of the abaecin derivative and cecropin B showed bacteriolytic activity 2 to 3 times greater than that of abaecin alone. CONCLUSIONS: Using a SUMO-tag with an appropriate codon-optimization strategy could be an approach for the production of antimicrobial peptides in E.coli without affecting the viability of the host cell. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12896-019-0506-x) contains supplementary material, which is available to authorized users.",2019 Feb 15,"['Kim, Da Sol', 'Kim, Seon Woong', 'Song, Jae Min', 'Kim, Soon Young', 'Kwon, Kwang-Chul']",BMC Biotechnol,,,False
9fb0b05599ed5c64ffbec62cf896434ed1c56349,PMC,A new prokaryotic expression vector for the expression of antimicrobial peptide abaecin using SUMO fusion tag,http://dx.doi.org/10.1186/s12896-019-0506-x,PMC6377777,30770741,CC BY,"BACKGROUND: Despite the growing demand for antimicrobial peptides (AMPs) for clinical use as an alternative approach against antibiotic-resistant bacteria, the manufacture of AMPs relies on expensive, small-scale chemical methods. The small ubiquitin-related modifier (SUMO) tag is industrially practical for increasing the yield of recombinant proteins by increasing solubility and preventing degradation in expression systems. RESULTS: A new vector system, pKSEC1, was designed to produce AMPs, which can work in prokaryotic systems such as Escherichia coli and plant chloroplasts. 6xHis was tagged to SUMO for purification of SUMO-fused AMPs. Abaecin, a 34-aa-long antimicrobial peptide from honeybees, was expressed in a fusion form to 6xHis-SUMO in a new vector system to evaluate the prokaryotic expression platform of the antimicrobial peptides. The fusion sequences were codon-optimized in three different combinations and expressed in E. coli. The combination of the native SUMO sequence with codon-optimized abaecin showed the highest expression level among the three combinations, and most of the expressed fusion proteins were detected in soluble fractions. Cleavage of the SUMO tag by sumoase produced a 29-aa-long abaecin derivative with a C-terminal deletion. However, this abaecin derivative still retained the binding sequence for its target protein, DnaK. Antibacterial activity of the 29-aa long abaecin was tested against Bacillus subtilis alone or in combination with cecropin B. The combined treatment of the abaecin derivative and cecropin B showed bacteriolytic activity 2 to 3 times greater than that of abaecin alone. CONCLUSIONS: Using a SUMO-tag with an appropriate codon-optimization strategy could be an approach for the production of antimicrobial peptides in E.coli without affecting the viability of the host cell. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12896-019-0506-x) contains supplementary material, which is available to authorized users.",2019 Feb 15,"['Kim, Da Sol', 'Kim, Seon Woong', 'Song, Jae Min', 'Kim, Soon Young', 'Kwon, Kwang-Chul']",BMC Biotechnol,,,True
d7a55353f72476f71bb7437da54ee876acb7e0e2,PMC,A new prokaryotic expression vector for the expression of antimicrobial peptide abaecin using SUMO fusion tag,http://dx.doi.org/10.1186/s12896-019-0506-x,PMC6377777,30770741,CC BY,"BACKGROUND: Despite the growing demand for antimicrobial peptides (AMPs) for clinical use as an alternative approach against antibiotic-resistant bacteria, the manufacture of AMPs relies on expensive, small-scale chemical methods. The small ubiquitin-related modifier (SUMO) tag is industrially practical for increasing the yield of recombinant proteins by increasing solubility and preventing degradation in expression systems. RESULTS: A new vector system, pKSEC1, was designed to produce AMPs, which can work in prokaryotic systems such as Escherichia coli and plant chloroplasts. 6xHis was tagged to SUMO for purification of SUMO-fused AMPs. Abaecin, a 34-aa-long antimicrobial peptide from honeybees, was expressed in a fusion form to 6xHis-SUMO in a new vector system to evaluate the prokaryotic expression platform of the antimicrobial peptides. The fusion sequences were codon-optimized in three different combinations and expressed in E. coli. The combination of the native SUMO sequence with codon-optimized abaecin showed the highest expression level among the three combinations, and most of the expressed fusion proteins were detected in soluble fractions. Cleavage of the SUMO tag by sumoase produced a 29-aa-long abaecin derivative with a C-terminal deletion. However, this abaecin derivative still retained the binding sequence for its target protein, DnaK. Antibacterial activity of the 29-aa long abaecin was tested against Bacillus subtilis alone or in combination with cecropin B. The combined treatment of the abaecin derivative and cecropin B showed bacteriolytic activity 2 to 3 times greater than that of abaecin alone. CONCLUSIONS: Using a SUMO-tag with an appropriate codon-optimization strategy could be an approach for the production of antimicrobial peptides in E.coli without affecting the viability of the host cell. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12896-019-0506-x) contains supplementary material, which is available to authorized users.",2019 Feb 15,"['Kim, Da Sol', 'Kim, Seon Woong', 'Song, Jae Min', 'Kim, Soon Young', 'Kwon, Kwang-Chul']",BMC Biotechnol,,,True
da2087c111ef9c8894c1dd1644d66a3aca35de9e,PMC,Benefits and Inputs From Lactic Acid Bacteria and Their Bacteriocins as Alternatives to Antibiotic Growth Promoters During Food-Animal Production,http://dx.doi.org/10.3389/fmicb.2019.00057,PMC6378274,30804896,CC BY,"Resistance to antibiotics is escalating and threatening humans and animals worldwide. Different countries have legislated or promoted the ban of antibiotics as growth promoters in livestock and aquaculture to reduce this phenomenon. Therefore, to improve animal growth and reproduction performance and to control multiple bacterial infections, there is a potential to use probiotics as non-antibiotic growth promoters. Lactic acid bacteria (LAB) offer various advantages as potential probiotics and can be considered as alternatives to antibiotics during food-animal production. LAB are safe microorganisms with abilities to produce different inhibitory compounds such as bacteriocins, organic acids as lactic acid, hydrogen peroxide, diacetyl, and carbon dioxide. LAB can inhibit harmful microorganisms with their arsenal, or through competitive exclusion mechanism based on competition for binding sites and nutrients. LAB endowed with specific enzymatic functions (amylase, protease…) can improve nutrients acquisition as well as animal immune system stimulation. This review aimed at underlining the benefits and inputs from LAB as potential alternatives to antibiotics in poultry, pigs, ruminants, and aquaculture production.",2019 Feb 11,"['Vieco-Saiz, Nuria', 'Belguesmia, Yanath', 'Raspoet, Ruth', 'Auclair, Eric', 'Gancel, Frédérique', 'Kempf, Isabelle', 'Drider, Djamel']",Front Microbiol,,,True
03797126b6e6689cc02878e641e5271d3b9a5d3b,PMC,An anti-Gn glycoprotein antibody from a convalescent patient potently inhibits the infection of severe fever with thrombocytopenia syndrome virus,http://dx.doi.org/10.1371/journal.ppat.1007375,PMC6380599,30707748,CC BY,"Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease localized to China, Japan, and Korea that is characterized by severe hemorrhage and a high fatality rate. Currently, no specific vaccine or treatment has been approved for this disease. To develop a therapeutic agent for SFTS, we isolated antibodies from a phage-displayed antibody library that was constructed from a patient who recovered from SFTS virus (SFTSV) infection. One antibody, designated as Ab10, was reactive to the Gn envelope glycoprotein of SFTSV and protected host cells and A129 mice from infection in both in vitro and in vivo experiments. Notably, Ab10 protected 80% of mice, even when injected 5 days after inoculation with a lethal dose of SFTSV. Using cross-linker assisted mass spectrometry and alanine scanning, we located the non-linear epitope of Ab10 on the Gn glycoprotein domain II and an unstructured stem region, suggesting that Ab10 may inhibit a conformational alteration that is critical for cell membrane fusion between the virus and host cell. Ab10 reacted to recombinant Gn glycoprotein in Gangwon/Korea/2012, HB28, and SD4 strains. Additionally, based on its epitope, we predict that Ab10 binds the Gn glycoprotein in 247 of 272 SFTSV isolates previously reported. Together, these data suggest that Ab10 has potential to be developed into a therapeutic agent that could protect against more than 90% of reported SFTSV isolates.",2019 Feb 1,"['Kim, Ki Hyun', 'Kim, Jinhee', 'Ko, Meehyun', 'Chun, June Young', 'Kim, Hyori', 'Kim, Seungtaek', 'Min, Ji-Young', 'Park, Wan Beom', 'Oh, Myoung-don', 'Chung, Junho']",PLoS Pathog,,,True
9086eb76194c342aad54afa61106a7c8883ef43b,PMC,Influence of Obesity on Pneumococcus Infection Risk in the Elderly,http://dx.doi.org/10.3389/fendo.2019.00071,PMC6381016,30814978,CC BY,"Obesity negatively affects immune function and host defense mechanisms. Obesity is associated with chronic activation of the innate immune system and consequent local and systemic inflammation which contribute to pathologic conditions such as type-2 diabetes mellitus, cancer, psoriasis, atherosclerosis, and inflammatory bowel disease. Individuals with obesity have increased susceptibility to contract viral, bacterial, and fungal infections and respond sub-optimally to vaccination. In this review, we summarize research findings on the effects of obesity on immune responses to respiratory tract infections (RTI), focusing on Streptococcus pneumoniae (“pneumococcus”) infection, which is a major cause of morbidity and mortality in the US, causing community-acquired infections such as pneumonia, otitis media and meningitis. We show that the risk of infection is higher in elderly individuals and also in individuals of certain ethnic groups, although in a few reports obesity has been associated with better survival of individuals admitted to hospital with pneumococcus infection, a phenomenon known as “obesity paradox.” We discuss factors that are associated with increased risk of pneumococcal infection, such as recent infection with RTI, chronic medical conditions, and immunosuppressive medications.",2019 Feb 13,"['Frasca, Daniela', 'McElhaney, Janet']",Front Endocrinol (Lausanne),,,True
97a0381dad9c04b6a53300885acd274d88d4f4d3,PMC,Viral infection detection using metagenomics technology in six poultry farms of eastern China,http://dx.doi.org/10.1371/journal.pone.0211553,PMC6382132,30785912,CC BY,"With rapidly increasing animal pathogen surveillance requirements, new technologies are needed for a comprehensive understanding of the roles of pathogens in the occurrence and development of animal diseases. We applied metagenomic technology to avian virus surveillance to study the main viruses infecting six poultry farms in two provinces in eastern China. Cloacal/throat double swabs were collected from 60 birds at each farm according to a random sampling method. The results showed that the method could simultaneously detect major viruses infecting farms, including avian influenza virus, infectious bronchitis virus, Newcastle disease virus, rotavirus G, duck hepatitis B virus, and avian leukemia virus subgroup J in several farms. The test results were consistent with the results from traditional polymerase chain reaction (PCR) or reverse transcription-PCR analyses. Five H9N2 and one H3N8 avian influenza viruses were detected at the farms and were identified as low pathogenic avian influenza viruses according to HA cleavage sites analysis. One detected Newcastle disease virus was classified as Class II genotype I and avirulent type according to F0 cleavage sites analysis. Three avian infectious bronchitis viruses were identified as 4/91, CK/CH/LSC/99I and TC07-2 genotypes by phylogenetic analysis of S1 genes. The viral infection surveillance method using metagenomics technology enables the monitoring of multiple viral infections, which allows the detection of main infectious viruses.",2019 Feb 20,"['Qiu, Yuan', 'Wang, Suchun', 'Huang, Baoxu', 'Zhong, Huanxiang', 'Pan, Zihao', 'Zhuang, Qingye', 'Peng, Cheng', 'Hou, Guangyu', 'Wang, Kaicheng']",PLoS One,,,True
7364053f8be4467970465443c10cc3b39e573137,PMC,Experimental Zika virus infection of Jamaican fruit bats (Artibeus jamaicensis) and possible entry of virus into brain via activated microglial cells,http://dx.doi.org/10.1371/journal.pntd.0007071,PMC6382173,30716104,CC BY,"The emergence of Zika virus (ZIKV) in the New World has led to more than 200,000 human infections. Perinatal infection can cause severe neurological complications, including fetal and neonatal microcephaly, and in adults there is an association with Guillain-Barré syndrome (GBS). ZIKV is transmitted to humans by Aedes sp. mosquitoes, yet little is known about its enzootic cycle in which transmission is thought to occur between arboreal Aedes sp. mosquitos and non-human primates. In the 1950s and ‘60s, several bat species were shown to be naturally and experimentally susceptible to ZIKV with acute viremia and seroconversion, and some developed neurological disease with viral antigen detected in the brain. Because of ZIKV emergence in the Americas, we sought to determine susceptibility of Jamaican fruit bats (Artibeus jamaicensis), one of the most common bats in the New World. Bats were inoculated with ZIKV PRVABC59 but did not show signs of disease. Bats held to 28 days post-inoculation (PI) had detectable antibody by ELISA and viral RNA was detected by qRT-PCR in the brain, saliva and urine in some of the bats. Immunoreactivity using polyclonal anti-ZIKV antibody was detected in testes, brain, lung and salivary glands plus scrotal skin. Tropism for mononuclear cells, including macrophages/microglia and fibroblasts, was seen in the aforementioned organs in addition to testicular Leydig cells. The virus likely localized to the brain via infection of Iba1(+) macrophage/microglial cells. Jamaican fruit bats, therefore, may be a useful animal model for the study of ZIKV infection. This work also raises the possibility that bats may have a role in Zika virus ecology in endemic regions, and that ZIKV may pose a wildlife disease threat to bat populations.",2019 Feb 4,"['Malmlov, Ashley', 'Bantle, Collin', 'Aboellail, Tawfik', 'Wagner, Kaitlyn', 'Campbell, Corey L.', 'Eckley, Miles', 'Chotiwan, Nunya', 'Gullberg, Rebekah C.', 'Perera, Rushika', 'Tjalkens, Ronald', 'Schountz, Tony']",PLoS Negl Trop Dis,,,True
e6a3a6591a7468ae5fdb3efcf43fa0dce1b0b00c,PMC,Using Pan RNA-Seq Analysis to Reveal the Ubiquitous Existence of 5′ and 3′ End Small RNAs,http://dx.doi.org/10.3389/fgene.2019.00105,PMC6382676,30838030,CC BY,"In this study, we used pan RNA-seq analysis to reveal the ubiquitous existence of both 5′ and 3′ end small RNAs (5′ and 3′ sRNAs). 5′ and 3′ sRNAs alone can be used to annotate nuclear non-coding and mitochondrial genes at 1-bp resolution and identify new steady RNAs, which are usually transcribed from functional genes. Then, we provided a simple and cost effective way for the annotation of nuclear non-coding and mitochondrial genes and the identification of new steady RNAs, particularly long non-coding RNAs (lncRNAs). Using 5′ and 3′ sRNAs, the annotation of human mitochondrial was corrected and a novel ncRNA named non-coding mitochondrial RNA 1 (ncMT1) was reported for the first time in this study. We also found that most of human tRNA genes have downstream lncRNA genes as lncTRS-TGA1-1 and corrected the misunderstanding of them in previous studies. Using 5′, 3′, and intronic sRNAs, we reported for the first time that enzymatic double-stranded RNA (dsRNA) cleavage and RNA interference (RNAi) might be involved in the RNA degradation and gene expression regulation of U1 snRNA in human. We provided a different perspective on the regulation of gene expression in U1 snRNA. We also provided a novel view on cancer and virus-induced diseases, leading to find diagnostics or therapy targets from the ribonuclease III (RNase III) family and its related pathways. Our findings pave the way toward a rediscovery of dsRNA cleavage and RNAi, challenging classical theories.",2019 Feb 14,"['Xu, Xiaofeng', 'Ji, Haishuo', 'Jin, Xiufeng', 'Cheng, Zhi', 'Yao, Xue', 'Liu, Yanqiang', 'Zhao, Qiang', 'Zhang, Tao', 'Ruan, Jishou', 'Bu, Wenjun', 'Chen, Ze', 'Gao, Shan']",Front Genet,,,True
11dcdcd827d9e2a609a7396a335d6c9891d99c28,PMC,Aerosol emission and superemission during human speech increase with voice loudness,http://dx.doi.org/10.1038/s41598-019-38808-z,PMC6382806,30787335,CC BY,"Mechanistic hypotheses about airborne infectious disease transmission have traditionally emphasized the role of coughing and sneezing, which are dramatic expiratory events that yield both easily visible droplets and large quantities of particles too small to see by eye. Nonetheless, it has long been known that normal speech also yields large quantities of particles that are too small to see by eye, but are large enough to carry a variety of communicable respiratory pathogens. Here we show that the rate of particle emission during normal human speech is positively correlated with the loudness (amplitude) of vocalization, ranging from approximately 1 to 50 particles per second (0.06 to 3 particles per cm(3)) for low to high amplitudes, regardless of the language spoken (English, Spanish, Mandarin, or Arabic). Furthermore, a small fraction of individuals behaves as “speech superemitters,” consistently releasing an order of magnitude more particles than their peers. Our data demonstrate that the phenomenon of speech superemission cannot be fully explained either by the phonic structures or the amplitude of the speech. These results suggest that other unknown physiological factors, varying dramatically among individuals, could affect the probability of respiratory infectious disease transmission, and also help explain the existence of superspreaders who are disproportionately responsible for outbreaks of airborne infectious disease.",2019 Feb 20,"['Asadi, Sima', 'Wexler, Anthony S.', 'Cappa, Christopher D.', 'Barreda, Santiago', 'Bouvier, Nicole M.', 'Ristenpart, William D.']",Sci Rep,,,True
8954feaa230060999c4f698c1582ffadfd79b0b9,PMC,Aerosol emission and superemission during human speech increase with voice loudness,http://dx.doi.org/10.1038/s41598-019-38808-z,PMC6382806,30787335,CC BY,"Mechanistic hypotheses about airborne infectious disease transmission have traditionally emphasized the role of coughing and sneezing, which are dramatic expiratory events that yield both easily visible droplets and large quantities of particles too small to see by eye. Nonetheless, it has long been known that normal speech also yields large quantities of particles that are too small to see by eye, but are large enough to carry a variety of communicable respiratory pathogens. Here we show that the rate of particle emission during normal human speech is positively correlated with the loudness (amplitude) of vocalization, ranging from approximately 1 to 50 particles per second (0.06 to 3 particles per cm(3)) for low to high amplitudes, regardless of the language spoken (English, Spanish, Mandarin, or Arabic). Furthermore, a small fraction of individuals behaves as “speech superemitters,” consistently releasing an order of magnitude more particles than their peers. Our data demonstrate that the phenomenon of speech superemission cannot be fully explained either by the phonic structures or the amplitude of the speech. These results suggest that other unknown physiological factors, varying dramatically among individuals, could affect the probability of respiratory infectious disease transmission, and also help explain the existence of superspreaders who are disproportionately responsible for outbreaks of airborne infectious disease.",2019 Feb 20,"['Asadi, Sima', 'Wexler, Anthony S.', 'Cappa, Christopher D.', 'Barreda, Santiago', 'Bouvier, Nicole M.', 'Ristenpart, William D.']",Sci Rep,,,True
4bc632592ca471bbff7effd71f3a9f930913f3c6,PMC,Variable 3’polyadenylation of Wheat yellow mosaic virus and its novel effects on translation and replication,http://dx.doi.org/10.1186/s12985-019-1130-z,PMC6383263,30786887,CC BY,"BACKGROUND: Polyadenylation influences many aspects of mRNA as well as viral RNA. variable polyadenylation at the 3' end have been reported in RNA viruses. It is interesting to identify the characteristic and potential role of 3' polyadenylation of Wheat yellow mosaic virus (WYMV), which has been reported to contain two genomic RNAs with 3' poly(A) tails and caused severe disease on wheat in East Asia region. METHODS: 3' RACE was used to identify sequences of the 3′ end in WYMV RNAs from naturally infected wheat by WYMV. In vitro translation assay was performed to analyze effect of UTRs of WYMV with or without 3’polyadenylation on translation. In vitro replication mediated by WYMV NIb protein were performed to evaluate effect of variable polyadenylation on replication. RESULTS: Variable polyadenylation in WYMV RNAs was identified via 3′ RACE. WYMV RNAs in naturally infected wheat in China simultaneously present with regions of long, short, or no adenylation at the 3' ends. The effects of variable polyadenylation on translation and replication of WYMV RNAs were evaluated. 5’UTR and 3’UTR of WYMV RNA1 or RNA2 synergistically enhanced the translation of the firefly luciferase (Fluc) gene in in vitro WGE system, whereas additional adenylates had an oppositive effect on this enhancement on translation mediated by UTRs of WYMV. Additional adenylates remarkably inhibited the synthesis of complementary strand from viral genome RNA during the in vitro replication mediated by WYMV NIb protein. CONCLUSIONS: 3' end of WYMV RNAs present variable polyadenylation even no polyadenylation. 3' polyadenylation have opposite effect on translation mediated by UTRs of WYMV RNA1 or RNA2. 3' polyadenylation have negative effect on minus-strand synthesis of WYMV RNA in vitro. Variable polyadenylation of WYMV RNAs may provide sufficient selection on the template for translation and replication. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-019-1130-z) contains supplementary material, which is available to authorized users.",2019 Feb 20,"['Geng, Guowei', 'Yu, Chengming', 'Li, Xiangdong', 'Yuan, Xuefeng']",Virol J,,,True
89a5f1619085d08f719fbf0b8bd1ac5bebd12187,PMC,Evaluation of the effectiveness of the SurePure Turbulator ultraviolet-C irradiation equipment on inactivation of different enveloped and non-enveloped viruses inoculated in commercially collected liquid animal plasma,http://dx.doi.org/10.1371/journal.pone.0212332,PMC6383881,30789926,CC BY,"The objective of this study was to evaluate the effectiveness of the SurePure Turbulator ultraviolet-C (UV-C, 254 nm wavelength) irradiation equipment on inactivation of different enveloped and non-enveloped viruses in commercially collected liquid animal plasma. Specifically, Pseudorabies virus (PRV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine epidemic diarrhea virus (PEDV), Bovine viral diarrhea virus (BVDV), Classical swine fever virus (CSFV), Swine influenza virus (SIV) as enveloped viruses and Porcine parvovirus (PPV), Swine vesicular disease virus (SVDV), Porcine circovirus type 2 (PCV-2) and Senecavirus A (SVA) as non-enveloped viruses, were inoculated in bovine or porcine plasma and subjected to different UV-C irradiation doses (0, 750, 1500, 3000, 6000 and 9000 J/L) using an UV-C device developed for opaque liquid working under turbulent flow. The enveloped viruses tested were inactivated at < 3000 J/L of UV-C, being the dose needed to inactivate 4 log TCID(50) (4D) of 1612 J/L for PRV,1004 J/L for PRRSV, 1953 J/L for PEDV, 1639 J/L for SIV, 1641 J/L for CSFV and 1943 J/L for BVDV. The non-enveloped viruses tended to have higher 4D values: 2161 J/L for PPV, 3223 J/L for SVA and 3708 J/L for SVDV. Because the initial viral concentration was <4.0 Log for PCV-2, it was not possible to calculate the 4D value for this virus. In conclusion, these results demonstrated that the SurePure Turbulator UV-C treatment system is capable of inactivating significant levels of swine viruses inoculated in commercially collected porcine or bovine plasma. It was concluded that irradiation with UV-C can provide an additional redundant biosafety feature in the manufacturing process of spray-dried animal plasma.",2019 Feb 21,"['Blázquez, Elena', 'Rodríguez, Carmen', 'Ródenas, Jesús', 'Navarro, Núria', 'Riquelme, Cristina', 'Rosell, Rosa', 'Campbell, Joy', 'Crenshaw, Joe', 'Segalés, Joaquim', 'Pujols, Joan', 'Polo, Javier']",PLoS One,,,True
8b724c562a6ee5b73e5ff058047e1cafd22b8cdd,PMC,Evaluation of the effectiveness of the SurePure Turbulator ultraviolet-C irradiation equipment on inactivation of different enveloped and non-enveloped viruses inoculated in commercially collected liquid animal plasma,http://dx.doi.org/10.1371/journal.pone.0212332,PMC6383881,30789926,CC BY,"The objective of this study was to evaluate the effectiveness of the SurePure Turbulator ultraviolet-C (UV-C, 254 nm wavelength) irradiation equipment on inactivation of different enveloped and non-enveloped viruses in commercially collected liquid animal plasma. Specifically, Pseudorabies virus (PRV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine epidemic diarrhea virus (PEDV), Bovine viral diarrhea virus (BVDV), Classical swine fever virus (CSFV), Swine influenza virus (SIV) as enveloped viruses and Porcine parvovirus (PPV), Swine vesicular disease virus (SVDV), Porcine circovirus type 2 (PCV-2) and Senecavirus A (SVA) as non-enveloped viruses, were inoculated in bovine or porcine plasma and subjected to different UV-C irradiation doses (0, 750, 1500, 3000, 6000 and 9000 J/L) using an UV-C device developed for opaque liquid working under turbulent flow. The enveloped viruses tested were inactivated at < 3000 J/L of UV-C, being the dose needed to inactivate 4 log TCID(50) (4D) of 1612 J/L for PRV,1004 J/L for PRRSV, 1953 J/L for PEDV, 1639 J/L for SIV, 1641 J/L for CSFV and 1943 J/L for BVDV. The non-enveloped viruses tended to have higher 4D values: 2161 J/L for PPV, 3223 J/L for SVA and 3708 J/L for SVDV. Because the initial viral concentration was <4.0 Log for PCV-2, it was not possible to calculate the 4D value for this virus. In conclusion, these results demonstrated that the SurePure Turbulator UV-C treatment system is capable of inactivating significant levels of swine viruses inoculated in commercially collected porcine or bovine plasma. It was concluded that irradiation with UV-C can provide an additional redundant biosafety feature in the manufacturing process of spray-dried animal plasma.",2019 Feb 21,"['Blázquez, Elena', 'Rodríguez, Carmen', 'Ródenas, Jesús', 'Navarro, Núria', 'Riquelme, Cristina', 'Rosell, Rosa', 'Campbell, Joy', 'Crenshaw, Joe', 'Segalés, Joaquim', 'Pujols, Joan', 'Polo, Javier']",PLoS One,,,False
aac1c9d5949eb6a98384e21c992a54d1eba166df,PMC,Evaluation of the effectiveness of the SurePure Turbulator ultraviolet-C irradiation equipment on inactivation of different enveloped and non-enveloped viruses inoculated in commercially collected liquid animal plasma,http://dx.doi.org/10.1371/journal.pone.0212332,PMC6383881,30789926,CC BY,"The objective of this study was to evaluate the effectiveness of the SurePure Turbulator ultraviolet-C (UV-C, 254 nm wavelength) irradiation equipment on inactivation of different enveloped and non-enveloped viruses in commercially collected liquid animal plasma. Specifically, Pseudorabies virus (PRV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine epidemic diarrhea virus (PEDV), Bovine viral diarrhea virus (BVDV), Classical swine fever virus (CSFV), Swine influenza virus (SIV) as enveloped viruses and Porcine parvovirus (PPV), Swine vesicular disease virus (SVDV), Porcine circovirus type 2 (PCV-2) and Senecavirus A (SVA) as non-enveloped viruses, were inoculated in bovine or porcine plasma and subjected to different UV-C irradiation doses (0, 750, 1500, 3000, 6000 and 9000 J/L) using an UV-C device developed for opaque liquid working under turbulent flow. The enveloped viruses tested were inactivated at < 3000 J/L of UV-C, being the dose needed to inactivate 4 log TCID(50) (4D) of 1612 J/L for PRV,1004 J/L for PRRSV, 1953 J/L for PEDV, 1639 J/L for SIV, 1641 J/L for CSFV and 1943 J/L for BVDV. The non-enveloped viruses tended to have higher 4D values: 2161 J/L for PPV, 3223 J/L for SVA and 3708 J/L for SVDV. Because the initial viral concentration was <4.0 Log for PCV-2, it was not possible to calculate the 4D value for this virus. In conclusion, these results demonstrated that the SurePure Turbulator UV-C treatment system is capable of inactivating significant levels of swine viruses inoculated in commercially collected porcine or bovine plasma. It was concluded that irradiation with UV-C can provide an additional redundant biosafety feature in the manufacturing process of spray-dried animal plasma.",2019 Feb 21,"['Blázquez, Elena', 'Rodríguez, Carmen', 'Ródenas, Jesús', 'Navarro, Núria', 'Riquelme, Cristina', 'Rosell, Rosa', 'Campbell, Joy', 'Crenshaw, Joe', 'Segalés, Joaquim', 'Pujols, Joan', 'Polo, Javier']",PLoS One,,,False
c35987c2bec71cee5cb373f4bff172b1bd24c474,PMC,Evaluation of the effectiveness of the SurePure Turbulator ultraviolet-C irradiation equipment on inactivation of different enveloped and non-enveloped viruses inoculated in commercially collected liquid animal plasma,http://dx.doi.org/10.1371/journal.pone.0212332,PMC6383881,30789926,CC BY,"The objective of this study was to evaluate the effectiveness of the SurePure Turbulator ultraviolet-C (UV-C, 254 nm wavelength) irradiation equipment on inactivation of different enveloped and non-enveloped viruses in commercially collected liquid animal plasma. Specifically, Pseudorabies virus (PRV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine epidemic diarrhea virus (PEDV), Bovine viral diarrhea virus (BVDV), Classical swine fever virus (CSFV), Swine influenza virus (SIV) as enveloped viruses and Porcine parvovirus (PPV), Swine vesicular disease virus (SVDV), Porcine circovirus type 2 (PCV-2) and Senecavirus A (SVA) as non-enveloped viruses, were inoculated in bovine or porcine plasma and subjected to different UV-C irradiation doses (0, 750, 1500, 3000, 6000 and 9000 J/L) using an UV-C device developed for opaque liquid working under turbulent flow. The enveloped viruses tested were inactivated at < 3000 J/L of UV-C, being the dose needed to inactivate 4 log TCID(50) (4D) of 1612 J/L for PRV,1004 J/L for PRRSV, 1953 J/L for PEDV, 1639 J/L for SIV, 1641 J/L for CSFV and 1943 J/L for BVDV. The non-enveloped viruses tended to have higher 4D values: 2161 J/L for PPV, 3223 J/L for SVA and 3708 J/L for SVDV. Because the initial viral concentration was <4.0 Log for PCV-2, it was not possible to calculate the 4D value for this virus. In conclusion, these results demonstrated that the SurePure Turbulator UV-C treatment system is capable of inactivating significant levels of swine viruses inoculated in commercially collected porcine or bovine plasma. It was concluded that irradiation with UV-C can provide an additional redundant biosafety feature in the manufacturing process of spray-dried animal plasma.",2019 Feb 21,"['Blázquez, Elena', 'Rodríguez, Carmen', 'Ródenas, Jesús', 'Navarro, Núria', 'Riquelme, Cristina', 'Rosell, Rosa', 'Campbell, Joy', 'Crenshaw, Joe', 'Segalés, Joaquim', 'Pujols, Joan', 'Polo, Javier']",PLoS One,,,False
2f10cd7b6249a3e9e55501f270f39a62c982981d,PMC,Evaluation of the effectiveness of the SurePure Turbulator ultraviolet-C irradiation equipment on inactivation of different enveloped and non-enveloped viruses inoculated in commercially collected liquid animal plasma,http://dx.doi.org/10.1371/journal.pone.0212332,PMC6383881,30789926,CC BY,"The objective of this study was to evaluate the effectiveness of the SurePure Turbulator ultraviolet-C (UV-C, 254 nm wavelength) irradiation equipment on inactivation of different enveloped and non-enveloped viruses in commercially collected liquid animal plasma. Specifically, Pseudorabies virus (PRV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine epidemic diarrhea virus (PEDV), Bovine viral diarrhea virus (BVDV), Classical swine fever virus (CSFV), Swine influenza virus (SIV) as enveloped viruses and Porcine parvovirus (PPV), Swine vesicular disease virus (SVDV), Porcine circovirus type 2 (PCV-2) and Senecavirus A (SVA) as non-enveloped viruses, were inoculated in bovine or porcine plasma and subjected to different UV-C irradiation doses (0, 750, 1500, 3000, 6000 and 9000 J/L) using an UV-C device developed for opaque liquid working under turbulent flow. The enveloped viruses tested were inactivated at < 3000 J/L of UV-C, being the dose needed to inactivate 4 log TCID(50) (4D) of 1612 J/L for PRV,1004 J/L for PRRSV, 1953 J/L for PEDV, 1639 J/L for SIV, 1641 J/L for CSFV and 1943 J/L for BVDV. The non-enveloped viruses tended to have higher 4D values: 2161 J/L for PPV, 3223 J/L for SVA and 3708 J/L for SVDV. Because the initial viral concentration was <4.0 Log for PCV-2, it was not possible to calculate the 4D value for this virus. In conclusion, these results demonstrated that the SurePure Turbulator UV-C treatment system is capable of inactivating significant levels of swine viruses inoculated in commercially collected porcine or bovine plasma. It was concluded that irradiation with UV-C can provide an additional redundant biosafety feature in the manufacturing process of spray-dried animal plasma.",2019 Feb 21,"['Blázquez, Elena', 'Rodríguez, Carmen', 'Ródenas, Jesús', 'Navarro, Núria', 'Riquelme, Cristina', 'Rosell, Rosa', 'Campbell, Joy', 'Crenshaw, Joe', 'Segalés, Joaquim', 'Pujols, Joan', 'Polo, Javier']",PLoS One,,,False
b952307f004f6feab9b3ae2cbee6d14f28ef9b4d,PMC,Molecular Basis of the Differentiation and Function of Virus Specific Follicular Helper CD4(+) T Cells,http://dx.doi.org/10.3389/fimmu.2019.00249,PMC6384271,30828337,CC BY,"During viral infection, virus-specific follicular helper T cells provide important help to cognate B cells for their survival, consecutive proliferation and mutation and eventual differentiation into memory B cells and antibody-secreting plasma cells. Similar to Tfh cells generated in other conditions, the differentiation of virus-specific Tfh cells can also be characterized as a process involved multiple factors and stages, however, which also exhibits distinct features. Here, we mainly focus on the current understanding of Tfh fate commitment, functional maturation, lineage maintenance and memory transition and formation in the context of viral infection.",2019 Feb 15,"['Huang, Qizhao', 'Hu, Jianjun', 'Tang, Jianfang', 'Xu, Lifan', 'Ye, Lilin']",Front Immunol,,,True
33cf03ea72e45ea6d6beeccc91c5145807544728,PMC,Developing Novel G-Quadruplex Ligands: From Interaction with Nucleic Acids to Interfering with Nucleic Acid–Protein Interaction,http://dx.doi.org/10.3390/molecules24030396,PMC6384609,30678288,CC BY,"G-quadruplex is a special secondary structure of nucleic acids in guanine-rich sequences of genome. G-quadruplexes have been proved to be involved in the regulation of replication, DNA damage repair, and transcription and translation of oncogenes or other cancer-related genes. Therefore, targeting G-quadruplexes has become a novel promising anti-tumor strategy. Different kinds of small molecules targeting the G-quadruplexes have been designed, synthesized, and identified as potential anti-tumor agents, including molecules directly bind to the G-quadruplex and molecules interfering with the binding between the G-quadruplex structures and related binding proteins. This review will explore the feasibility of G-quadruplex ligands acting as anti-tumor drugs, from basis to application. Meanwhile, since helicase is the most well-defined G-quadruplex-related protein, the most extensive research on the relationship between helicase and G-quadruplexes, and its meaning in drug design, is emphasized.",2019 Jan 22,"['Sun, Zhi-Yin', 'Wang, Xiao-Na', 'Cheng, Sui-Qi', 'Su, Xiao-Xuan', 'Ou, Tian-Miao']",Molecules,,,True
5f3a91dcea8198642e968d058fdb0c42cc1730d8,PMC,Octa-repeat domain of the mammalian prion protein mRNA forms stable A-helical hairpin structure rather than G-quadruplexes,http://dx.doi.org/10.1038/s41598-019-39213-2,PMC6384910,30792490,CC BY,"Misfolding and aggregation of prion protein (PrP) causes neurodegenerative diseases like Creutzfeldt-Jakob disease (CJD) and scrapie. Besides the consensus that spontaneous conversion of normal cellular PrP(C) into misfolded and aggregating PrP(Sc) is the central event in prion disease, an alternative hypothesis suggests the generation of pathological PrP(Sc) by rare translational frameshifting events in the octa-repeat domain of the PrP mRNA. Ribosomal frameshifting most commonly relies on a slippery site and an adjacent stable RNA structure to stall translating ribosome. Hence, it is crucial to unravel the secondary structure of the octa-repeat domain of PrP mRNA. Each of the five octa-repeats contains a motif (GGCGGUGGUGGCUGGG) which alone in vitro forms a G-quadruplex. Since the propensity of mRNA to form secondary structure depends on the sequence context, we set to determine the structure of the complete octa-repeat region. We assessed the structure of full-length octa-repeat domain of PrP mRNA using dynamic light scattering (DLS), small angle X-ray scattering (SAXS), circular dichroism (CD) spectroscopy and selective 2′-hydroxyl acylation analysis by primer extension (SHAPE). Our data show that the PrP octa-repeat mRNA forms stable A-helical hairpins with no evidence of G-quadruplex structure even in the presence of G-quadruplex stabilizing agents.",2019 Feb 21,"['Czech, Andreas', 'Konarev, Petr V.', 'Goebel, Ingrid', 'Svergun, Dmitri I.', 'Wills, Peter R.', 'Ignatova, Zoya']",Sci Rep,,,True
3bd73eb99e264efe1eb26301ea1fe67e8916aa6c,PMC,Octa-repeat domain of the mammalian prion protein mRNA forms stable A-helical hairpin structure rather than G-quadruplexes,http://dx.doi.org/10.1038/s41598-019-39213-2,PMC6384910,30792490,CC BY,"Misfolding and aggregation of prion protein (PrP) causes neurodegenerative diseases like Creutzfeldt-Jakob disease (CJD) and scrapie. Besides the consensus that spontaneous conversion of normal cellular PrP(C) into misfolded and aggregating PrP(Sc) is the central event in prion disease, an alternative hypothesis suggests the generation of pathological PrP(Sc) by rare translational frameshifting events in the octa-repeat domain of the PrP mRNA. Ribosomal frameshifting most commonly relies on a slippery site and an adjacent stable RNA structure to stall translating ribosome. Hence, it is crucial to unravel the secondary structure of the octa-repeat domain of PrP mRNA. Each of the five octa-repeats contains a motif (GGCGGUGGUGGCUGGG) which alone in vitro forms a G-quadruplex. Since the propensity of mRNA to form secondary structure depends on the sequence context, we set to determine the structure of the complete octa-repeat region. We assessed the structure of full-length octa-repeat domain of PrP mRNA using dynamic light scattering (DLS), small angle X-ray scattering (SAXS), circular dichroism (CD) spectroscopy and selective 2′-hydroxyl acylation analysis by primer extension (SHAPE). Our data show that the PrP octa-repeat mRNA forms stable A-helical hairpins with no evidence of G-quadruplex structure even in the presence of G-quadruplex stabilizing agents.",2019 Feb 21,"['Czech, Andreas', 'Konarev, Petr V.', 'Goebel, Ingrid', 'Svergun, Dmitri I.', 'Wills, Peter R.', 'Ignatova, Zoya']",Sci Rep,,,True
afe59f82672ff792a00e11e74e4ff6d9e560dc0d,PMC,Estimation of the effective reproduction number of influenza based on weekly reports in Miyazaki Prefecture,http://dx.doi.org/10.1038/s41598-019-39057-w,PMC6384943,30796315,CC BY,"In Japan, as part of surveillance for seasonal influenza, the number of patients per influenza sentinel site is counted on a weekly basis. Currently, reference values are set for the weekly reported number of influenza cases per sentinel, and pre-epidemic and epidemic warnings are issued based on these values. In this study, we examined the association between these reference values and the effective reproduction number (R(t)) using surveillance data for Miyazaki Prefecture collected from 2010 to 2011. There are nine public health centre jurisdictions in this prefecture, and R(t) exceeded 1.0 at the time when pre-epidemic warnings were issued in almost all the jurisdictions. Thus, it was indicated that the validity of the reference value was also high for influenza transmission. However, our results indicated the presence of secondary epidemic caused by infections originating both from other jurisdictions and inner jurisdictions, and it is occasionally not possible to evaluate the end of an epidemic in a jurisdiction using only the reference value of termination. It is necessary to establish new methods after considering the situation in the surrounding jurisdictions for more detailed epidemic predictions.",2019 Feb 22,"['Yamauchi, Takenori', 'Takeuchi, Shouhei', 'Yamano, Yuko', 'Kuroda, Yoshiki', 'Nakadate, Toshio']",Sci Rep,,,True
871eb9f53e30a9b67bd226ca8235a50c576a2755,PMC,A method to identify respiratory virus infections in clinical samples using next-generation sequencing,http://dx.doi.org/10.1038/s41598-018-37483-w,PMC6384955,30796243,CC BY,"Respiratory virus infections are very common. Such infections impose an enormous economic burden and occasionally lead to death. Furthermore, every few decades, respiratory virus pandemics emerge, putting the entire world population at risk. Thus, there is an urgent need to quickly and precisely identify the infecting agent in a clinical setting. However, in many patients with influenza-like symptoms (ILS) the identity of the underlying pathogen remains unknown. In addition, it takes time and effort to individually identify the virus responsible for the ILS. Here, we present a new next-generation sequencing (NGS)-based method that enables rapid and robust identification of pathogens in a pool of clinical samples without the need for specific primers. The method is aimed at rapidly uncovering a potentially common pathogen affecting many samples with an unidentified source of disease.",2019 Feb 22,"['Kustin, Talia', 'Ling, Guy', 'Sharabi, Sivan', 'Ram, Daniela', 'Friedman, Nehemya', 'Zuckerman, Neta', 'Bucris, Efrat Dahan', 'Glatman-Freedman, Aharona', 'Stern, Adi', 'Mandelboim, Michal']",Sci Rep,,,True
7f3006a21336451caedf41ab1791299a49831cc1,PMC,A Spotlight on Viruses—Application of Click Chemistry to Visualize Virus-Cell Interactions,http://dx.doi.org/10.3390/molecules24030481,PMC6385038,30700005,CC BY,"The replication of a virus within its host cell involves numerous interactions between viral and cellular factors, which have to be tightly controlled in space and time. The intricate interplay between viral exploitation of cellular pathways and the intrinsic host defense mechanisms is difficult to unravel by traditional bulk approaches. In recent years, novel fluorescence microscopy techniques and single virus tracking have transformed the investigation of dynamic virus-host interactions. A prerequisite for the application of these imaging-based methods is the attachment of a fluorescent label to the structure of interest. However, their small size, limited coding capacity and multifunctional proteins render viruses particularly challenging targets for fluorescent labeling approaches. Click chemistry in conjunction with genetic code expansion provides virologists with a novel toolbox for site-specific, minimally invasive labeling of virion components, whose potential has just recently begun to be exploited. Here, we summarize recent achievements, current developments and future challenges for the labeling of viral nucleic acids, proteins, glycoproteins or lipids using click chemistry in order to study dynamic processes in virus-cell interactions.",2019 Jan 29,"['Müller, Thorsten G.', 'Sakin, Volkan', 'Müller, Barbara']",Molecules,,,True
fd9eed8cf2f273870fcf73d0559f07dffb2f300c,PMC,On the predictability of infectious disease outbreaks,http://dx.doi.org/10.1038/s41467-019-08616-0,PMC6385200,30796206,CC BY,"Infectious disease outbreaks recapitulate biology: they emerge from the multi-level interaction of hosts, pathogens, and environment. Therefore, outbreak forecasting requires an integrative approach to modeling. While specific components of outbreaks are predictable, it remains unclear whether fundamental limits to outbreak prediction exist. Here, adopting permutation entropy as a model independent measure of predictability, we study the predictability of a diverse collection of outbreaks and identify a fundamental entropy barrier for disease time series forecasting. However, this barrier is often beyond the time scale of single outbreaks, implying prediction is likely to succeed. We show that forecast horizons vary by disease and that both shifting model structures and social network heterogeneity are likely mechanisms for differences in predictability. Our results highlight the importance of embracing dynamic modeling approaches, suggest challenges for performing model selection across long time series, and may relate more broadly to the predictability of complex adaptive systems.",2019 Feb 22,"['Scarpino, Samuel V.', 'Petri, Giovanni']",Nat Commun,,,False
02b20ad26d6b2f05b38712292186edbf3aa05862,PMC,On the predictability of infectious disease outbreaks,http://dx.doi.org/10.1038/s41467-019-08616-0,PMC6385200,30796206,CC BY,"Infectious disease outbreaks recapitulate biology: they emerge from the multi-level interaction of hosts, pathogens, and environment. Therefore, outbreak forecasting requires an integrative approach to modeling. While specific components of outbreaks are predictable, it remains unclear whether fundamental limits to outbreak prediction exist. Here, adopting permutation entropy as a model independent measure of predictability, we study the predictability of a diverse collection of outbreaks and identify a fundamental entropy barrier for disease time series forecasting. However, this barrier is often beyond the time scale of single outbreaks, implying prediction is likely to succeed. We show that forecast horizons vary by disease and that both shifting model structures and social network heterogeneity are likely mechanisms for differences in predictability. Our results highlight the importance of embracing dynamic modeling approaches, suggest challenges for performing model selection across long time series, and may relate more broadly to the predictability of complex adaptive systems.",2019 Feb 22,"['Scarpino, Samuel V.', 'Petri, Giovanni']",Nat Commun,,,True
8fc871d3cd3d6bb6981bebb026942df214442035,PMC,On the predictability of infectious disease outbreaks,http://dx.doi.org/10.1038/s41467-019-08616-0,PMC6385200,30796206,CC BY,"Infectious disease outbreaks recapitulate biology: they emerge from the multi-level interaction of hosts, pathogens, and environment. Therefore, outbreak forecasting requires an integrative approach to modeling. While specific components of outbreaks are predictable, it remains unclear whether fundamental limits to outbreak prediction exist. Here, adopting permutation entropy as a model independent measure of predictability, we study the predictability of a diverse collection of outbreaks and identify a fundamental entropy barrier for disease time series forecasting. However, this barrier is often beyond the time scale of single outbreaks, implying prediction is likely to succeed. We show that forecast horizons vary by disease and that both shifting model structures and social network heterogeneity are likely mechanisms for differences in predictability. Our results highlight the importance of embracing dynamic modeling approaches, suggest challenges for performing model selection across long time series, and may relate more broadly to the predictability of complex adaptive systems.",2019 Feb 22,"['Scarpino, Samuel V.', 'Petri, Giovanni']",Nat Commun,,,False
ce2d071c2152f86f8f190bb30ea857f16050ae8d,PMC,On the predictability of infectious disease outbreaks,http://dx.doi.org/10.1038/s41467-019-08616-0,PMC6385200,30796206,CC BY,"Infectious disease outbreaks recapitulate biology: they emerge from the multi-level interaction of hosts, pathogens, and environment. Therefore, outbreak forecasting requires an integrative approach to modeling. While specific components of outbreaks are predictable, it remains unclear whether fundamental limits to outbreak prediction exist. Here, adopting permutation entropy as a model independent measure of predictability, we study the predictability of a diverse collection of outbreaks and identify a fundamental entropy barrier for disease time series forecasting. However, this barrier is often beyond the time scale of single outbreaks, implying prediction is likely to succeed. We show that forecast horizons vary by disease and that both shifting model structures and social network heterogeneity are likely mechanisms for differences in predictability. Our results highlight the importance of embracing dynamic modeling approaches, suggest challenges for performing model selection across long time series, and may relate more broadly to the predictability of complex adaptive systems.",2019 Feb 22,"['Scarpino, Samuel V.', 'Petri, Giovanni']",Nat Commun,,,True
f93f20813c626fb775bbb73b1c14c906cd61e899,PMC,Identification of Neutralizing Monoclonal Antibodies Targeting Novel Conformational Epitopes of the Porcine Epidemic Diarrhoea Virus Spike Protein,http://dx.doi.org/10.1038/s41598-019-39844-5,PMC6385244,30792462,CC BY,"Since 2010, newly identified variants of porcine epidemic diarrhoea virus (PEDV) have caused high mortality in neonatal piglets which has devastated the swine industry. The spike (S) glycoprotein of PEDV contains multiple neutralizing epitopes and is a major target for PEDV neutralization and vaccine development. To understand the antigenicity of the new PEDV variant, we characterized the neutralizing epitopes of a new genotype 2b PEDV isolate from Taiwan, PEDV Pintung 52 (PEDV-PT), by the generation of neutralizing monoclonal antibodies (NmAbs). Two NmAbs, P4B-1, and E10E-1–10 that recognized the ectodomain of the full-length recombinant PEDV S protein and exhibited neutralizing ability against the PEDV-PT virus were selected. Recombinant truncated S proteins were used to identify the target sequences for the NmAbs and P4B-1 was shown to recognize the C-terminus of CO-26K equivalent epitope (COE) at amino acids (a.a.) 575–639 of the PEDV S. Interestingly, E10E-1–10 could recognize a novel neutralizing epitope at a.a. 435–485 within the S1(A) domain of the PEDV S protein, whose importance and function are yet to be determined. Moreover, both NmAbs could not bind to linearized S proteins, indicating that only conformational epitopes are recognized. This data could improve our understanding of the antigenic structures of the PEDV S protein and facilitate future development of novel epitope-based vaccines.",2019 Feb 21,"['Chang, Chia-Yu', 'Cheng, Ivan-Chen', 'Chang, Yen-Chen', 'Tsai, Pei-Shiue', 'Lai, Seiu-Yu', 'Huang, Yu-Liang', 'Jeng, Chian-Ren', 'Pang, Victor Fei', 'Chang, Hui-Wen']",Sci Rep,,,True
c601e38de42c9188e237fe848d26c4a7c07c3d58,PMC,A Transgenic Flock House Virus Replicon Reveals an RNAi Independent Antiviral Mechanism Acting in Drosophila Follicular Somatic Cells,http://dx.doi.org/10.1534/g3.118.200872,PMC6385967,30530643,CC BY,"The small interfering RNA (siRNA) pathway is the main and best studied invertebrate antiviral response. Other poorly characterized protein based antiviral mechanisms also contribute to the control of viral replication in insects. In addition, it remains unclear whether tissue specific factors contribute to RNA and protein-based antiviral immunity mechanisms. In vivo screens to identify such factors are challenging and time consuming. In addition, the scored phenotype is usually limited to survival and/or viral load. Transgenic viral replicons are valuable tools to overcome these limitations and screen for novel antiviral factors. Here we describe transgenic Drosophila melanogaster lines encoding a Flock House Virus-derived replicon (FHV∆B2eGFP), expressing GFP as a reporter of viral replication. This replicon is efficiently controlled by the siRNA pathway in most somatic tissues, with GFP fluorescence providing a reliable marker for the activity of antiviral RNAi. Interestingly, in follicular somatic cells (FSC) of ovaries, this replicon is still partially repressed in an siRNA independent manner. We did not detect replicon derived Piwi-interacting RNAs in FSCs and identified 31 differentially expressed genes between restrictive and permissive FSCs. Altogether, our results uncovered a yet unidentified RNAi-independent mechanism controlling FHV replication in FSCs of ovaries and validate the FHV∆B2eGFP replicon as a tool to screen for novel tissue specific antiviral mechanisms.",2018 Dec 12,"['Martins, Nelson', 'Lemoine, Aurélie', 'Santiago, Estelle', 'Paro, Simona', 'Imler, Jean-Luc', 'Meignin, Carine']",G3 (Bethesda),,,True
c1b41ee52ac37d6d0543d4e3ad9fd4df61dc2f07,PMC,Emerging Regulatory Roles of Dual-Specificity Phosphatases in Inflammatory Airway Disease,http://dx.doi.org/10.3390/ijms20030678,PMC6387402,30764493,CC BY,"Inflammatory airway disease, such as asthma and chronic obstructive pulmonary disease (COPD), is a major health burden worldwide. These diseases cause large numbers of deaths each year due to airway obstruction, which is exacerbated by respiratory viral infection. The inflammatory response in the airway is mediated in part through the MAPK pathways: p38, JNK and ERK. These pathways also have roles in interferon production, viral replication, mucus production, and T cell responses, all of which are important processes in inflammatory airway disease. Dual-specificity phosphatases (DUSPs) are known to regulate the MAPKs, and roles for this family of proteins in the pathogenesis of airway disease are emerging. This review summarizes the function of DUSPs in regulation of cytokine expression, mucin production, and viral replication in the airway. The central role of DUSPs in T cell responses, including T cell activation, differentiation, and proliferation, will also be highlighted. In addition, the importance of this protein family in the lung, and the necessity of further investigation into their roles in airway disease, will be discussed.",2019 Feb 5,"['Manley, Grace C. A.', 'Parker, Lisa C.', 'Zhang, Yongliang']",Int J Mol Sci,,,True
a8a9aa42224ef1fe08733dda2169f2e18ce6e92d,PMC,Transboundary spread of pig diseases: the role of international trade and travel,http://dx.doi.org/10.1186/s12917-019-1800-5,PMC6387505,30795759,CC BY,"As globalization increases the interconnectedness between nations, economies, and industries, the introduction of diseases will continue to remain a prominent threat to the livestock sector and the trade of animals and animal products, as well as the livelihoods of farmers, food security and public health. The global pig sector, with its size and dichotomy between production type and biosecurity level, is particularly vulnerable to the transmission of transboundary animal diseases such as African and classical swine fever, foot and mouth disease, or porcine reproductive and respiratory syndrome. All of the above pose a constant threat to swine health, mainly as a result of both formal and informal international trade. Inspired in the risk assessment methodology, this paper classifies and provides an overview of the different pig disease introduction and exposure pathways, illustrated with abundant examples. Introduction pathways are classified as formal international trade (by product), informal international trade (by product), and spread through fomites. Formal trade of pigs and pork products is regulated by legislation and measures protecting animal populations from exotic diseases. Much more difficult to control is the transboundary swine disease transmission originating through informal trade, which entails illegal smuggling, but also the informal cross-border transfer of animals and products for personal use or within informal market chains. Meat products are most commonly mentioned, although fomites have also played a role in some cases, with live pigs, being more difficult to smuggle playing a role less frequently. The main exposure pathways are also described with the oral route playing a prominent role. Risk assessments can aid in the identification of pathways of pathogen introduction and exposure. However, quantitative information on informal disease introduction pathways remains very scarce and often incomplete, making it difficult to estimate the actual magnitudes of risks. Nevertheless, this knowledge is deemed essential to set up risk based awareness, prevention and surveillance programs that correspond to reality.",2019 Feb 22,"['Beltran-Alcrudo, Daniel', 'Falco, John R.', 'Raizman, Eran', 'Dietze, Klaas']",BMC Vet Res,,,True
e0dbc66f68bc3baa8294c1fea46d8940f8a692db,PMC,Mapping novel genetic loci associated with female liver weight variations using Collaborative Cross mice,http://dx.doi.org/10.1002/ame2.12036,PMC6388055,30891567,CC BY,"BACKGROUND: Liver weight is a complex trait, controlled by polygenic factors and differs within populations. Dissecting the genetic architecture underlying these variations will facilitate the search for key role candidate genes involved directly in the hepatomegaly process and indirectly involved in related diseases etiology. METHODS: Liver weight of 506 mice generated from 39 different Collaborative Cross (CC) lines with both sexes at age 20 weeks old was determined using an electronic balance. Genomic DNA of the CC lines was genotyped with high‐density single nucleotide polymorphic markers. RESULTS: Statistical analysis revealed a significant (P < 0.05) variation of liver weight between the CC lines, with broad sense heritability (H (2)) of 0.32 and genetic coefficient of variation (CV(G)) of 0.28. Subsequently, quantitative trait locus (QTL) mapping was performed, and results showed a significant QTL only for females on chromosome 8 at genomic interval 88.61‐93.38 Mb (4.77 Mb). Three suggestive QTL were mapped at chromosomes 4, 12 and 13. The four QTL were designated as LWL1‐LWL4 referring to liver weight loci 1‐4 on chromosomes 8, 4, 12 and 13, respectively. CONCLUSION: To our knowledge, this report presents, for the first time, the utilization of the CC for mapping QTL associated with baseline liver weight in mice. Our findings demonstrate that liver weight is a complex trait controlled by multiple genetic factors that differ significantly between sexes.",2018 Oct 24,"['Abu‐Toamih Atamni, Hanifa J.', 'Botzman, Maya', 'Mott, Richard', 'Gat‐Viks, Irit', 'Iraqi, Fuad A.']",Animal Model Exp Med,,,True
d3aee39816e64957bf5d940e787330f152e71efe,PMC,Cross protective immune responses in nursing piglets infected with a US spike-insertion deletion porcine epidemic diarrhea virus strain and challenged with an original US PEDV strain,http://dx.doi.org/10.1186/s13567-017-0469-7,PMC6389210,28985754,CC BY,"We investigated cross-protective immunity of a US spike-insertion deletion porcine epidemic diarrhea virus (PEDV) Iowa106 (S-INDEL) strain against the original US PEDV (PC21A) strain in nursing piglets. Piglets were inoculated orally with S-INDEL, PC21A or mock. At 20–29 days post-inoculation (dpi), all pigs were challenged with the PC21A strain. The S-INDEL-inoculated pigs had lower ileal IgA antibody secreting cells, serum IgA and neutralizing antibody titers compared with PC21A-inoculated pigs. No pigs in the PC21A-group developed diarrhea, whereas 81 and 100% of pigs in the S-INDEL and mock-groups had diarrhea post challenge, respectively. S-INDEL induced partial protective immunity against the original US PEDV strain.",2017 Oct 6,"['Annamalai, Thavamathi', 'Lin, Chun-Ming', 'Gao, Xiang', 'Liu, Xinsheng', 'Lu, Zhongyan', 'Saif, Linda J.', 'Wang, Qiuhong']",Vet Res,,,True
5cb67b8103fed813182562e341dd55edb81c4998,PMC,"Respiratory syncytial virus prolifically infects N2a neuronal cells, leading to TLR4 and nucleolin protein modulations and RSV F protein co-localization with TLR4 and nucleolin",http://dx.doi.org/10.1186/s12929-018-0416-6,PMC6389248,29427996,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) infects the central nervous system, resulting in neurological symptoms. However, the precise underlying pathogenic mechanisms have not been elucidated. In the present study, the infectivity of RSV on N2a neuronal cells and the possible roles of Toll-like receptor 4 (TLR4) and nucleolin (C23) during RSV infection were investigated. METHODS: We compared two experimental groups (infected and non-infected) and monitored the RSV viral titers in the culture supernatant by a viral plaque assay. We also inspected the morphology of the nucleus in infected N2a cells. We measured the level of RSV F protein and studied its co-localization with TLR4 and nucleolin using immunofluorescence assays and laser confocal microscopy. The potential interaction of RSV F protein with TLR4 and nucleolin was examined by coimmunoprecipitation. The expression changes of TLR4, nucleolin, TLR3 and TLR7 proteins in N2a cells and IL-6 and TNF-α in the culture supernatant were investigated by Western Blot analysis and ELISA assay. Changes in neuronal cell apoptosis status was examined by flow cytometry. RESULTS: The results demonstrated prolific RSV infection of N2a cells, which triggered a decrease of NeuN protein expression, coinciding with an increase of nuclear lesions, F protein expression, RSV viral titers, and late apoptotic levels of N2a cells. RSV infection induced co-localization of RSV F protein with TLR4 and nucleolin, which could potentially lead to a direct interaction. Furthermore, it was found that TLR4 and nucleolin levels increased early after infection and decreased subsequently, whereas TLR3 and TLR7 expression increased throughout RSV infection. CONCLUSION: The RSV Long strain can prolifically infect N2a neuronal cells, modulating the expression of TLR4 and nucleolin, as well as TLR3, TLR7 and their downstream inflammatory factors, and inducing the co-localization of the RSV F protein with TLR4 and nucleolin.",2018 Feb 10,"['Yuan, Xiaoling', 'Hu, Tao', 'He, Hanwen', 'Qiu, Huan', 'Wu, Xuan', 'Chen, Jingxian', 'Wang, Minmin', 'Chen, Cheng', 'Huang, Shenghai']",J Biomed Sci,,,True
00c19aff3efc6e6430f77d81580ac927990ad5a2,PMC,Utility of bronchoalveolar lavage in the management of immunocompromised patients presenting with lung infiltrates,http://dx.doi.org/10.1186/s12890-019-0801-2,PMC6390608,30808314,CC BY,"BACKGROUND: Bronchoalveolar lavage (BAL) is utilized for diagnosing lung infiltrates in immunocompromised. There is heterogeneity in the data and reported diagnostic yields range from 26 to 69%. Therefore, selection criteria for BAL to maximize yield and minimize complications are unclear. Objectives of this study were to determine the diagnostic yield and complication rate of BAL in immunocompromised patients presenting with lung infiltrates, and identify factors impacting these outcomes. Exploratory aims included characterization of pathogens, rate of treatment modification and mortality. METHODS: Retrospective study from January 2012 to December 2016. Patients on mechanical ventilation were excluded. Positive diagnostic yield was defined as confirmed microbiological or cytological diagnosis. RESULTS: A total of 217 patients were recruited (70.1% male and mean age: 51.7 ± 14.6 years). Diagnostic yield was 60.8% and complication rate 14.7%. Complications (hypoxemia and endobronchial bleeding) were all sell-limiting. Treatment modification based on BAL results was 63.3%. In 97.0% an infectious aetiology was identified. HIV infection (OR 5.304, 95% CI 1.611–17.458, p = 0.006) and severe neutropenia (OR 4.253, 95% CI 1.288–14.045, p = 0.018) were associated with positive yield. Leukemia (OR 0.317, 95% CI 0.102–0.982, p = 0.047) was associated with lower yield. No factors impacted complication rate. Overall mortality (90-day) was 17.5% and in those with hematologic malignancy, it was 28.3%. CONCLUSION: BAL retains utility in diagnosis of immunocompromised patients with lung infiltrates. However, patients with hematologic malignancy have a high mortality and alternative sampling should be considered because of poor results with BAL. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01374542. Registered June 16, 2011.",2019 Feb 26,"['Choo, Randall', 'Naser, Naser Salman Hamza', 'Nadkarni, Nivedita Vikas', 'Anantham, Devanand']",BMC Pulm Med,,,True
4ed62784e978048e7494deb2f61a562c8140067e,PMC,Enrichment post-library preparation enhances the sensitivity of high-throughput sequencing-based detection and characterization of viruses from complex samples,http://dx.doi.org/10.1186/s12864-019-5543-2,PMC6390631,30808306,CC BY,"BACKGROUND: Sequencing-based detection and characterization of viruses in complex samples can suffer from lack of sensitivity due to a variety of factors including, but not limited to, low titer, small genome size, and contribution of host or environmental nucleic acids. Hybridization-based target enrichment is one potential method for increasing the sensitivity of viral detection via high-throughput sequencing. RESULTS: This study expands upon two previously developed panels of virus enrichment probes (for filoviruses and for respiratory viruses) to include other viruses of biodefense and/or biosurveillance concern to the U.S. Department of Defense and various international public health agencies. The newly expanded and combined panel is tested using carefully constructed synthetic metagenomic samples that contain clinically relevant amounts of viral genetic material. Target enrichment results in a dramatic increase in sensitivity for virus detection as compared to shotgun sequencing, yielding full, deeply covered viral genomes from materials with Ct values suggesting that amplicon sequencing would be likely to fail. Increased pooling to improve cost- and time-effectiveness does not negatively affect the ability to obtain full-length viral genomes, even in the case of co-infections, although as expected, it does decrease depth of coverage. CONCLUSIONS: Hybridization-based target enrichment is an effective solution to obtain full-length viral genomes for samples from which virus detection would fail via unbiased, shotgun sequencing or even via amplicon sequencing. As the development and testing of probe sets for viral target enrichment expands and continues, the application of this technique, in conjunction with deeper pooling strategies, could make high-throughput sequencing more economical for routine use in biosurveillance, biodefense and outbreak investigations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-019-5543-2) contains supplementary material, which is available to authorized users.",2019 Feb 26,"['Paskey, Adrian C.', 'Frey, Kenneth G.', 'Schroth, Gary', 'Gross, Stephen', 'Hamilton, Theron', 'Bishop-Lilly, Kimberly A.']",BMC Genomics,,,True
425007062aa63b14681dcf2414a0f5b77bca5ddd,PMC,Alignment-free similarity analysis for protein sequences based on fuzzy integral,http://dx.doi.org/10.1038/s41598-019-39477-8,PMC6391537,30808983,CC BY,"Sequence comparison is an essential part of modern molecular biology research. In this study, we estimated the parameters of Markov chain by considering the frequencies of occurrence of the all possible amino acid pairs from each alignment-free protein sequence. These estimated Markov chain parameters were used to calculate similarity between two protein sequences based on a fuzzy integral algorithm. For validation, our result was compared with both alignment-based (ClustalW) and alignment-free methods on six benchmark datasets. The results indicate that our developed algorithm has a better clustering performance for protein sequence comparison.",2019 Feb 26,"['Saw, Ajay Kumar', 'Tripathy, Binod Chandra', 'Nandi, Soumyadeep']",Sci Rep,,,True
89abb573b10d9a38b4724a0d38d91dfa6e162657,PMC,Alignment-free similarity analysis for protein sequences based on fuzzy integral,http://dx.doi.org/10.1038/s41598-019-39477-8,PMC6391537,30808983,CC BY,"Sequence comparison is an essential part of modern molecular biology research. In this study, we estimated the parameters of Markov chain by considering the frequencies of occurrence of the all possible amino acid pairs from each alignment-free protein sequence. These estimated Markov chain parameters were used to calculate similarity between two protein sequences based on a fuzzy integral algorithm. For validation, our result was compared with both alignment-based (ClustalW) and alignment-free methods on six benchmark datasets. The results indicate that our developed algorithm has a better clustering performance for protein sequence comparison.",2019 Feb 26,"['Saw, Ajay Kumar', 'Tripathy, Binod Chandra', 'Nandi, Soumyadeep']",Sci Rep,,,True
431b8b5c20edeb65055154ed5f93e8a9a49f4c97,PMC,Alignment-free similarity analysis for protein sequences based on fuzzy integral,http://dx.doi.org/10.1038/s41598-019-39477-8,PMC6391537,30808983,CC BY,"Sequence comparison is an essential part of modern molecular biology research. In this study, we estimated the parameters of Markov chain by considering the frequencies of occurrence of the all possible amino acid pairs from each alignment-free protein sequence. These estimated Markov chain parameters were used to calculate similarity between two protein sequences based on a fuzzy integral algorithm. For validation, our result was compared with both alignment-based (ClustalW) and alignment-free methods on six benchmark datasets. The results indicate that our developed algorithm has a better clustering performance for protein sequence comparison.",2019 Feb 26,"['Saw, Ajay Kumar', 'Tripathy, Binod Chandra', 'Nandi, Soumyadeep']",Sci Rep,,,True
856b6b5e0e5baedd6eef6801c3f59305438c47eb,PMC,Key Gaps in the Knowledge of the Porcine Respiratory Reproductive Syndrome Virus (PRRSV),http://dx.doi.org/10.3389/fvets.2019.00038,PMC6391865,30842948,CC BY,"The porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important swine diseases in the world. It is causing an enormous economic burden due to reproductive failure in sows and a complex respiratory syndrome in pigs of all ages, with mortality varying from 2 to 100% in the most extreme cases of emergent highly pathogenic strains. PRRSV displays complex interactions with the immune system and a high mutation rate, making the development, and implementation of control strategies a major challenge. In this review, the biology of the virus will be addressed focusing on newly discovered functions of non-structural proteins and novel dissemination mechanisms. Secondly, the role of different cell types and viral proteins will be reviewed in natural and vaccine-induced immune response together with the role of different immune evasion mechanisms focusing on those gaps of knowledge that are critical to generate more efficacious vaccines. Finally, novel strategies for antigen discovery and vaccine development will be discussed, in particular the use of exosomes (extracellular vesicles of endocytic origin). As nanocarriers of lipids, proteins and nucleic acids, exosomes have potential effects on cell activation, modulation of immune responses and antigen presentation. Thus, representing a novel vaccination approach against this devastating disease.",2019 Feb 20,"['Montaner-Tarbes, Sergio', 'del Portillo, Hernando A.', 'Montoya, María', 'Fraile, Lorenzo']",Front Vet Sci,,,True
a92d2df5aae260091456d3a65800c01cca79d599,PMC,Neutrophil Dysfunction in the Airways of Children with Acute Respiratory Failure Due to Lower Respiratory Tract Viral and Bacterial Coinfections,http://dx.doi.org/10.1038/s41598-019-39726-w,PMC6393569,30814584,CC BY,"Neutrophils are recruited to the airways of patients with acute respiratory distress syndrome (ARDS) where they acquire an activated pro-survival phenotype with an enhanced respiratory burst thought to contribute to ARDS pathophysiology. Our in vitro model enables blood neutrophil transepithelial migration into cell-free tracheal aspirate fluid from patients to recapitulate the primary airway neutrophil phenotype observed in vivo. Neutrophils transmigrated through our model toward airway fluid from children with lower respiratory viral infections coinfected with bacteria had elevated levels of neutrophil activation markers but paradoxically exhibited an inability to kill bacteria and a defective respiratory burst compared with children without bacterial coinfection. The airway fluid from children with bacterial coinfections had higher levels of neutrophil elastase activity, as well as myeloperoxidase levels compared to children without bacterial coinfection. Neutrophils transmigrated into the aspirate fluid from children with bacterial coinfection showed decreased respiratory burst and killing activity against H. influenzae and S. aureus compared to those transmigrated into the aspirate fluid from children without bacterial coinfection. Use of a novel transmigration model recapitulates this pathological phenotype in vitro that would otherwise be impossible in a patient, opening avenues for future mechanistic and therapeutic research.",2019 Feb 27,"['Grunwell, Jocelyn R.', 'Giacalone, Vincent D.', 'Stephenson, Susan', 'Margaroli, Camilla', 'Dobosh, Brian S.', 'Brown, Milton R.', 'Fitzpatrick, Anne M.', 'Tirouvanziam, Rabindra']",Sci Rep,,,True
ee92720c10a0cb395a8c1fd940dc0d12c44577f1,PMC,Counteraction of HCV-Induced Oxidative Stress Concurs to Establish Chronic Infection in Liver Cell Cultures,http://dx.doi.org/10.1155/2019/6452390,PMC6393922,30906503,CC BY,"Hepatitis C virus (HCV) is a blood-borne pathogen causing acute and chronic hepatitis. A significant number of people chronically infected with HCV develop cirrhosis and/or liver cancer. The pathophysiologic mechanisms of hepatocyte damage associated with chronic HCV infection are not fully understood yet, mainly due to the lack of an in vitro system able to recapitulate the stages of infection in vivo. Several studies underline that HCV virus replication depends on redox-sensitive cellular pathways; in addition, it is known that virus itself induces alterations of the cellular redox state. However, the exact interplay between HCV replication and oxidative stress has not been elucidated. In particular, the role of reduced glutathione (GSH) in HCV replication and infection is still not clear. We set up an in vitro system, based on low m.o.i. of Huh7.5 cell line with a HCV infectious clone (J6/JFH1), that reproduced the acute and persistent phases of HCV infection up to 76 days of culture. We demonstrated that the acute phase of HCV infection is characterized by the elevated levels of reactive oxygen species (ROS) associated in part with an increase of NADPH-oxidase transcripts and activity and a depletion of GSH accompanied by high rates of viral replication and apoptotic cell death. Conversely, the chronic phase is characterized by a reestablishment of reduced environment due to a decreased ROS production and increased GSH content in infected cells that might concur to the establishment of viral persistence. Treatment with the prooxidant auranofin of the persistently infected cultures induced the increase of viral RNA titer, suggesting that a prooxidant state could favor the reactivation of HCV viral replication that in turn caused cell damage and death. Our results suggest that targeting the redox-sensitive host-cells pathways essential for viral replication and/or persistence may represent a promising option for contrasting HCV infection.",2019 Feb 13,"['Anticoli, Simona', 'Amatore, Donatella', 'Matarrese, Paola', 'De Angelis, Marta', 'Palamara, Anna Teresa', 'Nencioni, Lucia', 'Ruggieri, Anna']",Oxid Med Cell Longev,,,True
725984c84bc703a34bc290f897e9f411ba3a67ec,PMC,"Bioaerosols and Transmission, a Diverse and Growing Community of Practice",http://dx.doi.org/10.3389/fpubh.2019.00023,PMC6394210,30847337,CC BY,"The transmission of infectious microbes via bioaerosols is of significant concern for both human and animal health. However, gaps in our understanding of respiratory pathogen transmission and methodological heterogeneity persist. New developments have enabled progress in this domain, and one of the major turning points has been the recognition that cross-disciplinary collaborations across spheres of human and animal health, microbiology, biophysics, engineering, aerobiology, infection control, public health, occupational health, and industrial hygiene are essential. Collaborative initiatives support advances in topics such as bioaerosol behavior, dispersion models, risk assessment, risk/exposure effects, and mitigation strategies in clinical, experimental, agricultural, and other field settings. There is a need to enhance the knowledge translation for researchers, stakeholders, and private partners to support a growing network of individuals and agencies to achieve common goals to mitigate inter- and intra-species pathogen transmission via bioaerosols.",2019 Feb 21,"['Mubareka, Samira', 'Groulx, Nicolas', 'Savory, Eric', 'Cutts, Todd', 'Theriault, Steven', 'Scott, James A.', 'Roy, Chad J.', 'Turgeon, Nathalie', 'Bryce, Elizabeth', 'Astrakianakis, George', 'Kirychuk, Shelley', 'Girard, Matthieu', 'Kobinger, Gary', 'Zhang, Chao', 'Duchaine, Caroline']",Front Public Health,,,True
c92206983f9523a96c8ea02210f70ee5640edd14,PMC,"Antibiotic misuse in respiratory tract infections in children and adults—a prospective, multicentre study (TAILORED Treatment)",http://dx.doi.org/10.1007/s10096-018-03454-2,PMC6394715,30707378,CC BY,"Respiratory tract infections (RTI) are more commonly caused by viral pathogens in children than in adults. Surprisingly, little is known about antibiotic use in children as compared to adults with RTI. This prospective study aimed to determine antibiotic misuse in children and adults with RTI, using an expert panel reference standard, in order to prioritise the target age population for antibiotic stewardship interventions. We recruited children and adults who presented at the emergency department or were hospitalised with clinical presentation of RTI in The Netherlands and Israel. A panel of three experienced physicians adjudicated a reference standard diagnosis (i.e. bacterial or viral infection) for all the patients using all available clinical and laboratory information, including a 28-day follow-up assessment. The cohort included 284 children and 232 adults with RTI (median age, 1.3 years and 64.5 years, respectively). The proportion of viral infections was larger in children than in adults (209(74%) versus 89(38%), p < 0.001). In case of viral RTI, antibiotics were prescribed (i.e. overuse) less frequently in children than in adults (77/209 (37%) versus 74/89 (83%), p < 0.001). One (1%) child and three (2%) adults with bacterial infection were not treated with antibiotics (i.e. underuse); all were mild cases. This international, prospective study confirms major antibiotic overuse in patients with RTI. Viral infection is more common in children, but antibiotic overuse is more frequent in adults with viral RTI. Together, these findings support the need for effective interventions to decrease antibiotic overuse in RTI patients of all ages. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-018-03454-2) contains supplementary material, which is available to authorized users.",2019 Feb 1,"['van Houten, Chantal B.', 'Cohen, Asi', 'Engelhard, Dan', 'Hays, John P.', 'Karlsson, Roger', 'Moore, Edward', 'Fernández, David', 'Kreisberg, Racheli', 'Collins, Laurence V.', 'de Waal, Wouter', 'de Winter-de Groot, Karin M.', 'Wolfs, Tom F. W.', 'Meijers, Pieter', 'Luijk, Bart', 'Oosterheert, Jan Jelrik', 'Heijligenberg, Rik', 'Sankatsing, Sanjay U. C.', 'Bossink, Aik W. J.', 'Stubbs, Andrew', 'Stein, Michal', 'Reisfeld, Sharon', 'Klein, Adi', 'Rachmilevitch, Ronit', 'Ashkar, Jalal', 'Braverman, Itzhak', 'Kartun, Valery', 'Chistyakov, Irena', 'Bamberger, Ellen', 'Srugo, Isaac', 'Odeh, Majed', 'Schiff, Elad', 'Dotan, Yaniv', 'Boico, Olga', 'Navon, Roy', 'Friedman, Tom', 'Etshtein, Liat', 'Paz, Meital', 'Gottlieb, Tanya M.', 'Pri-Or, Ester', 'Kronenfeld, Gali', 'Simon, Einav', 'Oved, Kfir', 'Eden, Eran', 'Bont, Louis J.']",Eur J Clin Microbiol Infect Dis,,,True
295d0e530c6b6d9df5c46872c36bf15dc85507fa,PMC,"Prevalence of Wēnzhōu virus in small mammals in Yunnan Province, China",http://dx.doi.org/10.1371/journal.pntd.0007049,PMC6395006,30768614,CC BY,"BACKGROUND: Mammarenaviruses are associated with human hemorrhagic fever diseases in Africa and America. Recently, a rodent mammarenavirus, Wēnzhōu virus (WENV) and related viruses, have been reported in China, Cambodia, and Thailand. Moreover, in Cambodia, these viruses were suspected to be associated with human disease. In China, Yunnan Province is famous for its abundant animal and plant diversity and is adjacent to several South-eastern Asia countries. Therefore, it is necessary to know whether WENV-related viruses, or other mammarenaviruses, are prevalent in this province. METHODOLOGY/PRINCIPAL FINDINGS: Small mammals were trapped, euthanized, and sampled. Mammarenavirus RNA was detected using a nested reverse transcription polymerase chain reaction (RT-PCR) and quantified by real-time RT-PCR. A total of 1040 small mammals belonging to 13 genera and 26 species were trapped in Yunnan Province. WENV-related mammarenaviruses were detected in 41 rodent liver samples, mainly in brown rats (Rattus norvegicus) and oriental house rats (R. tanezumi).Viral nucleocapsid protein was detected in liver sections by indirect immunofluorescence assay. Full-length-genomes were amplified by RT-PCR and used for phylogenetic analysis with the MEGA package. Recombination analysis was performed using the SimPlot and Recombination Detection Program. CONCLUSIONS/SIGNIFICANCE: WENV related viruses circulated in small mammals in Yunnan Province. Whole genome sequence analysis of five selected viral strains showed that these viruses are closely related to WENVs discovered in Asia and form an independent branch in the phylogenetic tree in the WENV clade. Paying attention to investigate the influence of these viruses to public health is essential in the epidemic regions.",2019 Feb 15,"['Wang, Jinxia', 'Yang, Xinglou', 'Liu, Haizhou', 'Wang, Li', 'Zhou, Jihua', 'Han, Xi', 'Zhu, Yan', 'Yang, Weihong', 'Pan, Hong', 'Zhang, Yunzhi', 'Shi, Zhengli']",PLoS Negl Trop Dis,,,True
55dc3ccae37d88301441558752efbc4700c116e3,PMC,PEDV and PDCoV Pathogenesis: The Interplay Between Host Innate Immune Responses and Porcine Enteric Coronaviruses,http://dx.doi.org/10.3389/fvets.2019.00034,PMC6395401,30854373,CC BY,"Enteropathogenic porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV), members of the coronavirus family, account for the majority of lethal watery diarrhea in neonatal pigs in the past decade. These two viruses pose significant economic and public health burdens, even as both continue to emerge and reemerge worldwide. The ability to evade, circumvent or subvert the host’s first line of defense, namely the innate immune system, is the key determinant for pathogen virulence, survival, and the establishment of successful infection. Unfortunately, we have only started to unravel the underlying viral mechanisms used to manipulate host innate immune responses. In this review, we gather current knowledge concerning the interplay between these viruses and components of host innate immunity, focusing on type I interferon induction and signaling in particular, and the mechanisms by which virus-encoded gene products antagonize and subvert host innate immune responses. Finally, we provide some perspectives on the advantages gained from a better understanding of host-pathogen interactions. This includes their implications for the future development of PEDV and PDCoV vaccines and how we can further our knowledge of the molecular mechanisms underlying virus pathogenesis, virulence, and host coevolution.",2019 Feb 22,"['Koonpaew, Surapong', 'Teeravechyan, Samaporn', 'Frantz, Phanramphoei Namprachan', 'Chailangkarn, Thanathom', 'Jongkaewwattana, Anan']",Front Vet Sci,,,True
d49187b9f472f85007b97606ae92699d506143ca,PMC,CRISPR-mediated activation of endogenous BST-2/tetherin expression inhibits wild-type HIV-1 production,http://dx.doi.org/10.1038/s41598-019-40003-z,PMC6395588,30816279,CC BY,"The CRISPR technology not only can knock out target genes by using the RNA-guided Cas9 nuclease but also can activate their expression when a nuclease-deficient Cas9 (dCas9) is employed. Using the latter function, we here show the effect of the CRISPR-mediated pinpoint activation of endogenous expression of BST-2 (also known as tetherin), a virus restriction factor with a broad antiviral spectrum. Single-guide RNA (sgRNA) sequences targeting the BST-2 promoter were selected by promoter assays. Potential sgRNAs and dCas9 fused to the VP64 transactivation domain, along with an accessory transcriptional activator complex, were introduced into cells by lentiviral transduction. Increased expression of BST-2 mRNA in transduced cells was confirmed by real-time RT-PCR. Cells in which BST-2 expression was highly enhanced showed the effective inhibition of HIV-1 production and replication even in the presence of the viral antagonist Vpu against BST-2. These findings confirm that the physiological stoichiometry between host restriction factors and viral antagonists may determine the outcome of the battle with viruses.",2019 Feb 28,"['Zhang, Yanzhao', 'Ozono, Seiya', 'Yao, Weitong', 'Tobiume, Minoru', 'Yamaoka, Shoji', 'Kishigami, Satoshi', 'Fujita, Hideaki', 'Tokunaga, Kenzo']",Sci Rep,,,False
8e08171efdeefb1359c606284d75271667ef8252,PMC,CRISPR-mediated activation of endogenous BST-2/tetherin expression inhibits wild-type HIV-1 production,http://dx.doi.org/10.1038/s41598-019-40003-z,PMC6395588,30816279,CC BY,"The CRISPR technology not only can knock out target genes by using the RNA-guided Cas9 nuclease but also can activate their expression when a nuclease-deficient Cas9 (dCas9) is employed. Using the latter function, we here show the effect of the CRISPR-mediated pinpoint activation of endogenous expression of BST-2 (also known as tetherin), a virus restriction factor with a broad antiviral spectrum. Single-guide RNA (sgRNA) sequences targeting the BST-2 promoter were selected by promoter assays. Potential sgRNAs and dCas9 fused to the VP64 transactivation domain, along with an accessory transcriptional activator complex, were introduced into cells by lentiviral transduction. Increased expression of BST-2 mRNA in transduced cells was confirmed by real-time RT-PCR. Cells in which BST-2 expression was highly enhanced showed the effective inhibition of HIV-1 production and replication even in the presence of the viral antagonist Vpu against BST-2. These findings confirm that the physiological stoichiometry between host restriction factors and viral antagonists may determine the outcome of the battle with viruses.",2019 Feb 28,"['Zhang, Yanzhao', 'Ozono, Seiya', 'Yao, Weitong', 'Tobiume, Minoru', 'Yamaoka, Shoji', 'Kishigami, Satoshi', 'Fujita, Hideaki', 'Tokunaga, Kenzo']",Sci Rep,,,True
34e218f77932d4c7a4c29c7a18010d846ee3f4a6,PMC,IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation,http://dx.doi.org/10.1002/eji.201847692,PMC6396086,30365177,CC BY,"The interferon‐inducible transmembrane (Ifitm/Fragilis) genes encode homologous proteins that are induced by IFNs. Here, we show that IFITM proteins regulate murine CD4(+) Th cell differentiation. Ifitm2 and Ifitm3 are expressed in wild‐type (WT) CD4(+) T cells. On activation, Ifitm3 was downregulated and Ifitm2 was upregulated. Resting Ifitm‐family‐deficient CD4(+) T cells had higher expression of Th1‐associated genes than WT and purified naive Ifitm‐family‐deficient CD4(+) T cells differentiated more efficiently to Th1, whereas Th2 differentiation was inhibited. Ifitm‐family‐deficient mice, but not Ifitm3‐deficient mice, were less susceptible than WT to induction of allergic airways disease, with a weaker Th2 response and less severe disease and lower Il4 but higher Ifng expression and IL‐27 secretion. Thus, the Ifitm family is important in adaptive immunity, influencing Th1/Th2 polarization, and Th2 immunopathology.",2019 Jan 9,"['Yánez, Diana C.', 'Sahni, Hemant', 'Ross, Susan', 'Solanki, Anisha', 'Lau, Ching‐In', 'Papaioannou, Eleftheria', 'Barbarulo, Alessandro', 'Powell, Rebecca', 'Lange, Ulrike C.', 'Adams, David J.', 'Barenco, Martino', 'Ono, Masahiro', ""D'Acquisto, Fulvio"", 'Furmanski, Anna L.', 'Crompton, Tessa']",Eur J Immunol,,,True
dc22742fe9f296e13c6d9b375fc35407d5c3609d,PMC,IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation,http://dx.doi.org/10.1002/eji.201847692,PMC6396086,30365177,CC BY,"The interferon‐inducible transmembrane (Ifitm/Fragilis) genes encode homologous proteins that are induced by IFNs. Here, we show that IFITM proteins regulate murine CD4(+) Th cell differentiation. Ifitm2 and Ifitm3 are expressed in wild‐type (WT) CD4(+) T cells. On activation, Ifitm3 was downregulated and Ifitm2 was upregulated. Resting Ifitm‐family‐deficient CD4(+) T cells had higher expression of Th1‐associated genes than WT and purified naive Ifitm‐family‐deficient CD4(+) T cells differentiated more efficiently to Th1, whereas Th2 differentiation was inhibited. Ifitm‐family‐deficient mice, but not Ifitm3‐deficient mice, were less susceptible than WT to induction of allergic airways disease, with a weaker Th2 response and less severe disease and lower Il4 but higher Ifng expression and IL‐27 secretion. Thus, the Ifitm family is important in adaptive immunity, influencing Th1/Th2 polarization, and Th2 immunopathology.",2019 Jan 9,"['Yánez, Diana C.', 'Sahni, Hemant', 'Ross, Susan', 'Solanki, Anisha', 'Lau, Ching‐In', 'Papaioannou, Eleftheria', 'Barbarulo, Alessandro', 'Powell, Rebecca', 'Lange, Ulrike C.', 'Adams, David J.', 'Barenco, Martino', 'Ono, Masahiro', ""D'Acquisto, Fulvio"", 'Furmanski, Anna L.', 'Crompton, Tessa']",Eur J Immunol,,,False
03cff1790e31683b4367f41b09f7efbbf2dc53e6,PMC,IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation,http://dx.doi.org/10.1002/eji.201847692,PMC6396086,30365177,CC BY,"The interferon‐inducible transmembrane (Ifitm/Fragilis) genes encode homologous proteins that are induced by IFNs. Here, we show that IFITM proteins regulate murine CD4(+) Th cell differentiation. Ifitm2 and Ifitm3 are expressed in wild‐type (WT) CD4(+) T cells. On activation, Ifitm3 was downregulated and Ifitm2 was upregulated. Resting Ifitm‐family‐deficient CD4(+) T cells had higher expression of Th1‐associated genes than WT and purified naive Ifitm‐family‐deficient CD4(+) T cells differentiated more efficiently to Th1, whereas Th2 differentiation was inhibited. Ifitm‐family‐deficient mice, but not Ifitm3‐deficient mice, were less susceptible than WT to induction of allergic airways disease, with a weaker Th2 response and less severe disease and lower Il4 but higher Ifng expression and IL‐27 secretion. Thus, the Ifitm family is important in adaptive immunity, influencing Th1/Th2 polarization, and Th2 immunopathology.",2019 Jan 9,"['Yánez, Diana C.', 'Sahni, Hemant', 'Ross, Susan', 'Solanki, Anisha', 'Lau, Ching‐In', 'Papaioannou, Eleftheria', 'Barbarulo, Alessandro', 'Powell, Rebecca', 'Lange, Ulrike C.', 'Adams, David J.', 'Barenco, Martino', 'Ono, Masahiro', ""D'Acquisto, Fulvio"", 'Furmanski, Anna L.', 'Crompton, Tessa']",Eur J Immunol,,,False
35c31daa44cb7fd28aeea422bb15d1a3858a2378,PMC,A system for production of defective interfering particles in the absence of infectious influenza A virus,http://dx.doi.org/10.1371/journal.pone.0212757,PMC6396908,30822349,CC BY,"Influenza A virus (IAV) infection poses a serious health threat and novel antiviral strategies are needed. Defective interfering particles (DIPs) can be generated in IAV infected cells due to errors of the viral polymerase and may suppress spread of wild type (wt) virus. The antiviral activity of DIPs is exerted by a DI genomic RNA segment that usually contains a large deletion and suppresses amplification of wt segments, potentially by competing for cellular and viral resources. DI-244 is a naturally occurring prototypic segment 1-derived DI RNA in which most of the PB2 open reading frame has been deleted and which is currently developed for antiviral therapy. At present, coinfection with wt virus is required for production of DI-244 particles which raises concerns regarding biosafety and may complicate interpretation of research results. Here, we show that cocultures of 293T and MDCK cell lines stably expressing codon optimized PB2 allow production of DI-244 particles solely from plasmids and in the absence of helper virus. Moreover, we demonstrate that infectivity of these particles can be quantified using MDCK-PB2 cells. Finally, we report that the DI-244 particles produced in this novel system exert potent antiviral activity against H1N1 and H3N2 IAV but not against the unrelated vesicular stomatitis virus. This is the first report of DIP production in the absence of infectious IAV and may spur efforts to develop DIPs for antiviral therapy.",2019 Mar 1,"['Bdeir, Najat', 'Arora, Prerna', 'Gärtner, Sabine', 'Hoffmann, Markus', 'Reichl, Udo', 'Pöhlmann, Stefan', 'Winkler, Michael']",PLoS One,,,True
d270606c783ef48aae93edcff93e82f8ef614a69,PMC,A system for production of defective interfering particles in the absence of infectious influenza A virus,http://dx.doi.org/10.1371/journal.pone.0212757,PMC6396908,30822349,CC BY,"Influenza A virus (IAV) infection poses a serious health threat and novel antiviral strategies are needed. Defective interfering particles (DIPs) can be generated in IAV infected cells due to errors of the viral polymerase and may suppress spread of wild type (wt) virus. The antiviral activity of DIPs is exerted by a DI genomic RNA segment that usually contains a large deletion and suppresses amplification of wt segments, potentially by competing for cellular and viral resources. DI-244 is a naturally occurring prototypic segment 1-derived DI RNA in which most of the PB2 open reading frame has been deleted and which is currently developed for antiviral therapy. At present, coinfection with wt virus is required for production of DI-244 particles which raises concerns regarding biosafety and may complicate interpretation of research results. Here, we show that cocultures of 293T and MDCK cell lines stably expressing codon optimized PB2 allow production of DI-244 particles solely from plasmids and in the absence of helper virus. Moreover, we demonstrate that infectivity of these particles can be quantified using MDCK-PB2 cells. Finally, we report that the DI-244 particles produced in this novel system exert potent antiviral activity against H1N1 and H3N2 IAV but not against the unrelated vesicular stomatitis virus. This is the first report of DIP production in the absence of infectious IAV and may spur efforts to develop DIPs for antiviral therapy.",2019 Mar 1,"['Bdeir, Najat', 'Arora, Prerna', 'Gärtner, Sabine', 'Hoffmann, Markus', 'Reichl, Udo', 'Pöhlmann, Stefan', 'Winkler, Michael']",PLoS One,,,False
3b47134b34fccfc681adc69656465f49349d83ca,PMC,An uncharacterized FMAG_01619 protein from Fusobacterium mortiferum ATCC 9817 demonstrates that some bacterial macrodomains can also act as poly-ADP-ribosylhydrolases,http://dx.doi.org/10.1038/s41598-019-39691-4,PMC6397177,30824723,CC BY,"Macrodomains constitute a conserved fold widely distributed that is not only able to bind ADP-ribose in its free and protein-linked forms but also can catalyse the hydrolysis of the latter. They are involved in the regulation of important cellular processes, such as signalling, differentiation, proliferation and apoptosis, and in host-virus response, and for this, they are considered as promising therapeutic targets to slow tumour progression and viral pathogenesis. Although extensive work has been carried out with them, including their classification into six distinct phylogenetically clades, little is known on bacterial macrodomains, especially if these latter are able to remove poly(ADP-ribose) polymer (PAR) from PARylated proteins, activity that only has been confirmed in human TARG1 (C6orf130) protein. To extend this limited knowledge, we demonstrate, after a comprehensive bioinformatic and phylogenetic analysis, that Fusobacterium mortiferum ATCC 9817 TARG1 (FmTARG1) is the first bacterial macrodomain shown to have high catalytic efficiency towards O-acyl-ADP-ribose, even more than hTARG1, and towards mono- and poly(ADPribosyl)ated proteins. Surprisingly, FmTARG1 gene is also inserted into a unique operonic context, only shared by the distantly related Fusobacterium perfoetens ATCC 29250 macrodomain, which include an immunity protein 51 domain, typical of bacterial polymorphic toxin systems.",2019 Mar 1,"['García-Saura, Antonio Ginés', 'Zapata-Pérez, Rubén', 'Hidalgo, José Francisco', 'Cabanes, Juana', 'Gil-Ortiz, Fernando', 'Sánchez-Ferrer, Álvaro']",Sci Rep,,,False
49a9a8769ece770dba1c78176dfe4264e51fad4b,PMC,An uncharacterized FMAG_01619 protein from Fusobacterium mortiferum ATCC 9817 demonstrates that some bacterial macrodomains can also act as poly-ADP-ribosylhydrolases,http://dx.doi.org/10.1038/s41598-019-39691-4,PMC6397177,30824723,CC BY,"Macrodomains constitute a conserved fold widely distributed that is not only able to bind ADP-ribose in its free and protein-linked forms but also can catalyse the hydrolysis of the latter. They are involved in the regulation of important cellular processes, such as signalling, differentiation, proliferation and apoptosis, and in host-virus response, and for this, they are considered as promising therapeutic targets to slow tumour progression and viral pathogenesis. Although extensive work has been carried out with them, including their classification into six distinct phylogenetically clades, little is known on bacterial macrodomains, especially if these latter are able to remove poly(ADP-ribose) polymer (PAR) from PARylated proteins, activity that only has been confirmed in human TARG1 (C6orf130) protein. To extend this limited knowledge, we demonstrate, after a comprehensive bioinformatic and phylogenetic analysis, that Fusobacterium mortiferum ATCC 9817 TARG1 (FmTARG1) is the first bacterial macrodomain shown to have high catalytic efficiency towards O-acyl-ADP-ribose, even more than hTARG1, and towards mono- and poly(ADPribosyl)ated proteins. Surprisingly, FmTARG1 gene is also inserted into a unique operonic context, only shared by the distantly related Fusobacterium perfoetens ATCC 29250 macrodomain, which include an immunity protein 51 domain, typical of bacterial polymorphic toxin systems.",2019 Mar 1,"['García-Saura, Antonio Ginés', 'Zapata-Pérez, Rubén', 'Hidalgo, José Francisco', 'Cabanes, Juana', 'Gil-Ortiz, Fernando', 'Sánchez-Ferrer, Álvaro']",Sci Rep,,,True
44eb5c174b0fe94bde674772bebd4312af33b355,PMC,Comparative Serological Study for the Prevalence of Anti-MERS Coronavirus Antibodies in High- and Low-Risk Groups in Qatar,http://dx.doi.org/10.1155/2019/1386740,PMC6398027,30906787,CC BY,"Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) could be asymptomatic or cause mild influenza-like illness. Therefore, the prevalence of MERS-CoV infections in the general population could be underestimated, which necessitates active surveillance to determine the epidemiological importance of asymptomatic cases. The aim of this study is to evaluate the performance of various serological assays and to estimate the seroprevalence of anti-MERS-CoV antibodies in high- and low-risk groups in Qatar. A total of 4858 samples were screened, including 4719 samples collected from healthy blood donors (BD) over a period of five years (2012-2016), 135 samples from baseline case contacts (CC) collected from individuals in close contact with three positive PCR-confirmed patients (CP), and four samples from MERS-CoV CP. Initial screening using anti-MERS-CoV IgG (IgG rS1-ELISA kit) revealed ten reactive samples from BD (10/4719, 0.21%), one from CC (1/135, 0.74%), and three from CP (3/4, 75%). Samples from CP but not from BD were also reactive by whole-virus anti-MERS-CoV IgG (n = 3/4) and IgM (n = 1/4) indirect immunefluorescent tests (IIFT) and pseudoparticle neutralization test (ppNT). The reactive sample from CC was also confirmed by ppNT. Surprisingly, one out of thirteen (7.7%) randomly selected IgG rS1-ELISA-negative BD samples from the initial screening was reactive by the IgM-IIFT (but not by the IgG-IIFT) and was subsequently confirmed by ppNT. All IgG rS1-ELISA-reactive samples from BD exhibited considerable reactivity to the four circulating human coronaviruses (HKU1, OC43, 229E, and NL63). Cross-reactivity with SARS was only reported for samples from CP using IgG and IgM-IIFT. In conclusion, we report a low prevalence of anti-MERS antibodies in the general population, which coincides with the low number of all reported cases by the time of our study (2017) in Qatar (n = 21). The false-positive results and the observed cross-reactivity between MERS-CoV and other circulating human coronavirus necessitate more detailed evaluation of available serological assays.",2019 Feb 18,"['Al Kahlout, Reham A.', 'Nasrallah, Gheyath K.', 'Farag, Elmoubasher A.', 'Wang, Lingshu', 'Lattwein, Erik', 'Müller, Marcel A.', 'El Zowalaty, Mohamed E.', 'Al Romaihi, Hamad E.', 'Graham, Barney S.', 'Al Thani, Asmaa A.', 'Yassine, Hadi M.']",J Immunol Res,,,True
423e1f15afb86012057acacc26d0766aa4bc582a,PMC,Interactions Between Enteroviruses and the Inflammasome: New Insights Into Viral Pathogenesis,http://dx.doi.org/10.3389/fmicb.2019.00321,PMC6398425,30858838,CC BY,"Enteroviruses (EVs) have emerged a substantial threat to public health. EVs infection range from mild to severe disease, including mild respiratory illness, diarrhea, poliomyelitis, hand, foot, and mouth disease, aseptic meningitis, and encephalitis. In the Asia-Pacific region, for example, one of the best studied enterovirus 71 (EV71) has been associated with pandemics of hand, foot, and mouth disease (HFMD) in children, particularly those under the age of five. Serious HFMD cases are associated with neurological complications, such as aseptic meningitis, acute flaccid paralysis, brainstem encephalitis, and have been associated with as many as 1000s of deaths in children and infants from 2008 to 2017, in China. More than 90% of laboratory confirmed deaths due to HMFD are associated with EV71. However, little is known about the pathogenesis of EVs. Studies have reported that EVs-infected patients with severe complications show elevated serum concentrations of IL-1β. The secretion of IL-1β is mediated by NLRP3 inflammasome during EV71 and CVB3 infection. Enteroviruses 2B and 3D proteins play an important role in activation of NLRP3 inflammasome, while 3C and 2A play important roles in antagonizing the activation of NLRP3 and the secretion of IL-1β. In this review, we summarize current knowledge regarding the molecular mechanisms that underlie the activation and regulation of the NLRP3 inflammasome, particularly how viral proteins regulate NLRP3 inflammasome activation. These insights into the relationship between the NLRP3 inflammasome and the pathogenesis of EVs infection may ultimately inform the development of novel antiviral drugs.",2019 Feb 25,"['Xiao, Xia', 'Qi, Jianli', 'Lei, Xiaobo', 'Wang, Jianwei']",Front Microbiol,,,True
519d5fa432c696fd94690fbffeb3d566a247019c,PMC,Reconstruction and prediction of viral disease epidemics,http://dx.doi.org/10.1017/S0950268818002881,PMC6398585,30394230,CC BY,"A growing number of infectious pathogens are spreading among geographic regions. Some pathogens that were previously not considered to pose a general threat to human health have emerged at regional and global scales, such as Zika and Ebola Virus Disease. Other pathogens, such as yellow fever virus, were previously thought to be under control but have recently re-emerged, causing new challenges to public health organisations. A wide array of new modelling techniques, aided by increased computing capabilities, novel diagnostic tools, and the increased speed and availability of genomic sequencing allow researchers to identify new pathogens more rapidly, assess the likelihood of geographic spread, and quantify the speed of human-to-human transmission. Despite some initial successes in predicting the spread of acute viral infections, the practicalities and sustainability of such approaches will need to be evaluated in the context of public health responses.",2018 Nov 5,"['Kraemer, M. U. G.', 'Cummings, D. A. T.', 'Funk, S.', 'Reiner, R. C.', 'Faria, N. R.', 'Pybus, O. G.', 'Cauchemez, S.']",Epidemiol Infect,,,True
e33688801d9c88a6e02f0cd0775b31ad8d911c58,PMC,Multiplex PCR methods for detection of several viruses associated with canine respiratory and enteric diseases,http://dx.doi.org/10.1371/journal.pone.0213295,PMC6398926,30830947,CC BY,"Viral respiratory and intestinal infections are the most common causes of canine viral illness. Infection with multiple pathogens occurs in many cases. Rapid diagnosis of these multiple infections is important for providing timely and effective treatment. To improve diagnosis, in this study, two new multiplex polymerase chain reactions (mPCRs) were developed for simultaneous detection of canine respiratory viruses (CRV) and canine enteric viruses (CEV) using two separate primer mixes. The viruses included canine adenovirus type 2 (CAV-2), canine distemper virus (CDV), canine influenza virus (CIV), canine parainfluenza virus (CPIV), canine circovirus (CanineCV), canine coronavirus (CCoV) and canine parvovirus (CPV). The sensitivity of the mPCR results showed that the detection limit of both mPCR methods was 1×10(4) viral copies. Twenty nasal swabs (NS) and 20 anal swabs (AS) collected from dogs with symptoms of respiratory disease or enteric disease were evaluated using the novel mPCR methods as a clinical test. The mPCR protocols, when applied to these respiratory specimens and intestinal samples, could detect 7 viruses simultaneously, allowing rapid investigation of CRV (CAV-2, CDV, CIV and CPIV) and CEV (CAV-2, CanineCV, CCoV and CPV) status and prompt evaluation of coinfection. Our study provides an effective and accurate tool for rapid differential diagnosis and epidemiological surveillance in dogs.",2019 Mar 4,"['Hao, Xiangqi', 'Liu, Ruohan', 'He, Yuwei', 'Xiao, Xiangyu', 'Xiao, Weiqi', 'Zheng, Qingxu', 'Lin, Xi', 'Tao, Pan', 'Zhou, Pei', 'Li, Shoujun']",PLoS One,,,True
4eb512e8b51929e92cae935e6355b1b571e9e7b0,PMC,Effectiveness of Integrative Therapy for Parkinson’s Disease Management,http://dx.doi.org/10.3389/fnagi.2019.00040,PMC6399136,30863304,CC BY,"Objectives: To investigate the effectiveness of integrative therapy on prevalence and length of hospitalization and management of major complications of Parkinson’s disease (PD) in the South Korea. Methods: This study was a retrospective cohort analysis conducted using the National Health Insurance Service-National Sample Cohort in the South Korea. Patients over 65 years old who were newly diagnosed with PD during 2007–2011 were identified. The integrative therapy group was defined as patients treated with both Korean medicine (KM) and biomedicine, and the monotherapy group consisted of patients treated with biomedicine alone. From PD diagnosis to 2013, the prevalence and annual length of hospitalization because of PD and major complications (dementia, depression and pneumonia/sepsis) were analyzed using logistic regression, ANOVA and t-tests after propensity score (PS) matching with a 1:1 ratio. Results: After PS estimation and matching, the cohort used in the analysis included 228 subjects (114 integrative therapy group, 114 monotherapy group). Sex, age, index year, comorbidity, severity of disability, neurologic care, and anti-parkinsonism medication (levodopa, ropinirole, pramipexole, selegiline) were adjusted in both groups. The prevalence of hospitalization due to pneumonia/sepsis was 0.50 times (95% C.I.: 0.26–0.96) lower in the integrative therapy group than the monotherapy group, which was statistically significant (p = 0.038). The prevalence and annual length of total hospitalization and hospitalization because of PD, dementia, and depression in the integrative therapy group showed positive results compared to the monotherapy group, but these differences were not statistically significant. Conclusion: It has not been clearly identified that integrative therapy with KM and biomedicine for PD management is better treatment for patients compared to biomedicine monotherapy; however, we found a clue of better result in integrated therapy. Therefore, further investigation by increasing the number of subjects is needed to confirm the findings presented herein.",2019 Feb 26,"['Woo, Yeonju', 'Hyun, Min Kyung']",Front Aging Neurosci,,,True
cf7d1c521ef8589d2ede65d742b0c8fa87d37d2e,PMC,Metagenomic Approach to Characterizing Disease Epidemiology in a Disease-Endemic Environment in Northern Thailand,http://dx.doi.org/10.3389/fmicb.2019.00319,PMC6399164,30863381,CC BY,"In this study, we used a metagenomic approach to analyze bacterial communities from diverse populations (humans, animals, and vectors) to investigate the role of these microorganisms as causative agents of disease in human and animal populations. Wild rodents and ectoparasites were collected from 2014 to 2018 in Nan province, Thailand where scrub typhus is highly endemic. Samples from undifferentiated febrile illness (UFI) patients were obtained from a local hospital. A total of 200 UFI patient samples were obtained and 309 rodents and 420 pools of ectoparasites were collected from rodents (n = 285) and domestic animals (n = 135). The bacterial 16S rRNA gene was amplified and sequenced with the Illumina. Real-time PCR and Sanger sequencing were used to confirm the next-generation sequencing (NGS) results and to characterize pathogen species. Several pathogens were detected by NGS in all populations studied and the most common pathogens identified included Bartonella spp., Rickettsia spp., Leptospira spp., and Orientia tsutsugamushi. Interestingly, Anaplasma spp. was detected in patient, rodent and tick populations, although they were not previously known to cause human disease from this region. Candidatus Neoehrlichia, Neorickettsia spp., Borrelia spp., and Ehrlichia spp. were detected in rodents and their associated ectoparasites. The same O. tsutsugamushi genotypes were shared among UFI patients, rodents, and chiggers in a single district indicating that the chiggers found on rodents were also likely responsible for transmitting to people. Serological testing using immunofluorescence assays in UFI samples showed high prevalence (IgM/IgG) of Rickettsia and Orientia pathogens, most notably among samples collected during September–November. Additionally, a higher number of seropositive samples belonged to patients in the working age population (20–60 years old). The results presented in this study demonstrate that the increased risk of human infection or exposure to chiggers and their associated pathogen (O. tsutsugamushi) resulted in part from two important factors; working age group and seasons for rice cultivation and harvesting. Evidence of pathogen exposure was shown to occur as there was seropositivity (IgG) in UFI patients for bartonellosis as well as for anaplasmosis. Using a metagenomic approach, this study demonstrated the circulation and transmission of several pathogens in the environment, some of which are known causative agents of illness in human populations.",2019 Feb 26,"['Takhampunya, Ratree', 'Korkusol, Achareeya', 'Pongpichit, Chalermpol', 'Yodin, Komsan', 'Rungrojn, Artharee', 'Chanarat, Nitima', 'Promsathaporn, Sommai', 'Monkanna, Taweesak', 'Thaloengsok, Sasikanya', 'Tippayachai, Bousaraporn', 'Kumfao, Naruemon', 'Richards, Allen L.', 'Davidson, Silas A.']",Front Microbiol,,,False
5479a0b2eb8bb566074e933d9e398fbb7db09ab1,PMC,Metagenomic Approach to Characterizing Disease Epidemiology in a Disease-Endemic Environment in Northern Thailand,http://dx.doi.org/10.3389/fmicb.2019.00319,PMC6399164,30863381,CC BY,"In this study, we used a metagenomic approach to analyze bacterial communities from diverse populations (humans, animals, and vectors) to investigate the role of these microorganisms as causative agents of disease in human and animal populations. Wild rodents and ectoparasites were collected from 2014 to 2018 in Nan province, Thailand where scrub typhus is highly endemic. Samples from undifferentiated febrile illness (UFI) patients were obtained from a local hospital. A total of 200 UFI patient samples were obtained and 309 rodents and 420 pools of ectoparasites were collected from rodents (n = 285) and domestic animals (n = 135). The bacterial 16S rRNA gene was amplified and sequenced with the Illumina. Real-time PCR and Sanger sequencing were used to confirm the next-generation sequencing (NGS) results and to characterize pathogen species. Several pathogens were detected by NGS in all populations studied and the most common pathogens identified included Bartonella spp., Rickettsia spp., Leptospira spp., and Orientia tsutsugamushi. Interestingly, Anaplasma spp. was detected in patient, rodent and tick populations, although they were not previously known to cause human disease from this region. Candidatus Neoehrlichia, Neorickettsia spp., Borrelia spp., and Ehrlichia spp. were detected in rodents and their associated ectoparasites. The same O. tsutsugamushi genotypes were shared among UFI patients, rodents, and chiggers in a single district indicating that the chiggers found on rodents were also likely responsible for transmitting to people. Serological testing using immunofluorescence assays in UFI samples showed high prevalence (IgM/IgG) of Rickettsia and Orientia pathogens, most notably among samples collected during September–November. Additionally, a higher number of seropositive samples belonged to patients in the working age population (20–60 years old). The results presented in this study demonstrate that the increased risk of human infection or exposure to chiggers and their associated pathogen (O. tsutsugamushi) resulted in part from two important factors; working age group and seasons for rice cultivation and harvesting. Evidence of pathogen exposure was shown to occur as there was seropositivity (IgG) in UFI patients for bartonellosis as well as for anaplasmosis. Using a metagenomic approach, this study demonstrated the circulation and transmission of several pathogens in the environment, some of which are known causative agents of illness in human populations.",2019 Feb 26,"['Takhampunya, Ratree', 'Korkusol, Achareeya', 'Pongpichit, Chalermpol', 'Yodin, Komsan', 'Rungrojn, Artharee', 'Chanarat, Nitima', 'Promsathaporn, Sommai', 'Monkanna, Taweesak', 'Thaloengsok, Sasikanya', 'Tippayachai, Bousaraporn', 'Kumfao, Naruemon', 'Richards, Allen L.', 'Davidson, Silas A.']",Front Microbiol,,,True
a33cbb1080496b58132dc8cae5e40c933d93ccd7,PMC,Identification and genetic characterization of a novel Orthobunyavirus species by a straightforward high-throughput sequencing-based approach,http://dx.doi.org/10.1038/s41598-019-40036-4,PMC6399452,30833612,CC BY,"Identification and characterization of novel unknown viruses is of great importance. The introduction of high-throughput sequencing (HTS)-based methods has paved the way for genomics-based detection of pathogens without any prior assumptions about the characteristics of the organisms. However, the use of HTS for the characterization of viral pathogens from clinical samples remains limited. Here, we report the identification of a novel Orthobunyavirus species isolated from horse plasma. The identification was based on a straightforward HTS approach. Following enrichment in cell culture, RNA was extracted from the growth medium and rapid library preparation, HTS and primary bioinformatic analyses were performed in less than 12 hours. Taxonomical profiling of the sequencing reads did not reveal sequence similarities to any known virus. Subsequent application of de novo assembly tools to the sequencing reads produced contigs, of which three showed some similarity to the L, M, and S segments of viruses belonging to the Orthobunyavirus genus. Further refinement of these contigs resulted in high-quality, full-length genomic sequences of the three genomic segments (L, M and S) of a novel Orthobunyavirus. Characterization of the genomic sequence, including the prediction of open reading frames and the inspection of consensus genomic termini and phylogenetic analysis, further confirmed that the novel virus is indeed a new species, which we named Ness Ziona virus.",2019 Mar 4,"['Shifman, Ohad', 'Cohen-Gihon, Inbar', 'Beth-Din, Adi', 'Zvi, Anat', 'Laskar, Orly', 'Paran, Nir', 'Epstein, Eyal', 'Stein, Dana', 'Dorozko, Marina', 'Wolf, Dana', 'Yitzhaki, Shmuel', 'Shapira, Shmuel C.', 'Melamed, Sharon', 'Israeli, Ofir']",Sci Rep,,,False
91c7bd831dbc0f6dbbdb2b6f344419a3cb970794,PMC,Identification and genetic characterization of a novel Orthobunyavirus species by a straightforward high-throughput sequencing-based approach,http://dx.doi.org/10.1038/s41598-019-40036-4,PMC6399452,30833612,CC BY,"Identification and characterization of novel unknown viruses is of great importance. The introduction of high-throughput sequencing (HTS)-based methods has paved the way for genomics-based detection of pathogens without any prior assumptions about the characteristics of the organisms. However, the use of HTS for the characterization of viral pathogens from clinical samples remains limited. Here, we report the identification of a novel Orthobunyavirus species isolated from horse plasma. The identification was based on a straightforward HTS approach. Following enrichment in cell culture, RNA was extracted from the growth medium and rapid library preparation, HTS and primary bioinformatic analyses were performed in less than 12 hours. Taxonomical profiling of the sequencing reads did not reveal sequence similarities to any known virus. Subsequent application of de novo assembly tools to the sequencing reads produced contigs, of which three showed some similarity to the L, M, and S segments of viruses belonging to the Orthobunyavirus genus. Further refinement of these contigs resulted in high-quality, full-length genomic sequences of the three genomic segments (L, M and S) of a novel Orthobunyavirus. Characterization of the genomic sequence, including the prediction of open reading frames and the inspection of consensus genomic termini and phylogenetic analysis, further confirmed that the novel virus is indeed a new species, which we named Ness Ziona virus.",2019 Mar 4,"['Shifman, Ohad', 'Cohen-Gihon, Inbar', 'Beth-Din, Adi', 'Zvi, Anat', 'Laskar, Orly', 'Paran, Nir', 'Epstein, Eyal', 'Stein, Dana', 'Dorozko, Marina', 'Wolf, Dana', 'Yitzhaki, Shmuel', 'Shapira, Shmuel C.', 'Melamed, Sharon', 'Israeli, Ofir']",Sci Rep,,,True
297cbd05451ec2c6158f48b859e881145892dc61,PMC,"Genetic control of the mouse HDL proteome defines HDL traits, function, and heterogeneity",http://dx.doi.org/10.1194/jlr.M090555,PMC6399512,30622162,CC BY,"HDLs are nanoparticles with more than 80 associated proteins, phospholipids, cholesterol, and cholesteryl esters. The potential inverse relation of HDL to coronary artery disease (CAD) and the effects of HDL on myriad other inflammatory conditions warrant a better understanding of the genetic basis of the HDL proteome. We conducted a comprehensive genetic analysis of the regulation of the proteome of HDL isolated from a panel of 100 diverse inbred strains of mice (the hybrid mouse diversity panel) and examined protein composition and efflux capacity to identify novel factors that affect the HDL proteome. Genetic analysis revealed widely varied HDL protein levels across the strains. Some of this variation was explained by local cis-acting regulation, termed cis-protein quantitative trait loci (QTLs). Variations in apoA-II and apoC-3 affected the abundance of multiple HDL proteins, indicating a coordinated regulation. We identified modules of covarying proteins and defined a protein-protein interaction network that describes the protein composition of the naturally occurring subspecies of HDL in mice. Sterol efflux capacity varied up to 3-fold across the strains, and HDL proteins displayed distinct correlation patterns with macrophage and ABCA1-specific cholesterol efflux capacity and cholesterol exchange, suggesting that subspecies of HDL participate in discrete functions. The baseline and stimulated sterol efflux capacity phenotypes were associated with distinct QTLs with smaller effect size, suggesting a multigenetic regulation. Our results highlight the complexity of HDL particles by revealing the high degree of heterogeneity and intercorrelation, some of which is associated with functional variation, and support the concept that HDL-cholesterol alone is not an accurate measure of HDL’s properties, such as protection against CAD.",2019 Mar 8,"['Pamir, Nathalie', 'Pan, Calvin', 'Plubell, Deanna L.', 'Hutchins, Patrick M.', 'Tang, Chongren', 'Wimberger, Jake', 'Irwin, Angela', 'Vallim, Thomas Q. de Aguiar', 'Heinecke, Jay W.', 'Lusis, Aldons J.']",J Lipid Res,,,False
e5d7b78cf1acf78071a1b54e6f4fe6dd68ac9430,PMC,"Genetic control of the mouse HDL proteome defines HDL traits, function, and heterogeneity",http://dx.doi.org/10.1194/jlr.M090555,PMC6399512,30622162,CC BY,"HDLs are nanoparticles with more than 80 associated proteins, phospholipids, cholesterol, and cholesteryl esters. The potential inverse relation of HDL to coronary artery disease (CAD) and the effects of HDL on myriad other inflammatory conditions warrant a better understanding of the genetic basis of the HDL proteome. We conducted a comprehensive genetic analysis of the regulation of the proteome of HDL isolated from a panel of 100 diverse inbred strains of mice (the hybrid mouse diversity panel) and examined protein composition and efflux capacity to identify novel factors that affect the HDL proteome. Genetic analysis revealed widely varied HDL protein levels across the strains. Some of this variation was explained by local cis-acting regulation, termed cis-protein quantitative trait loci (QTLs). Variations in apoA-II and apoC-3 affected the abundance of multiple HDL proteins, indicating a coordinated regulation. We identified modules of covarying proteins and defined a protein-protein interaction network that describes the protein composition of the naturally occurring subspecies of HDL in mice. Sterol efflux capacity varied up to 3-fold across the strains, and HDL proteins displayed distinct correlation patterns with macrophage and ABCA1-specific cholesterol efflux capacity and cholesterol exchange, suggesting that subspecies of HDL participate in discrete functions. The baseline and stimulated sterol efflux capacity phenotypes were associated with distinct QTLs with smaller effect size, suggesting a multigenetic regulation. Our results highlight the complexity of HDL particles by revealing the high degree of heterogeneity and intercorrelation, some of which is associated with functional variation, and support the concept that HDL-cholesterol alone is not an accurate measure of HDL’s properties, such as protection against CAD.",2019 Mar 8,"['Pamir, Nathalie', 'Pan, Calvin', 'Plubell, Deanna L.', 'Hutchins, Patrick M.', 'Tang, Chongren', 'Wimberger, Jake', 'Irwin, Angela', 'Vallim, Thomas Q. de Aguiar', 'Heinecke, Jay W.', 'Lusis, Aldons J.']",J Lipid Res,,,True
c9a6a3d79f58c4b3a62e2913aaa1d076e5abf7c3,PMC,Consequences of delays and imperfect implementation of isolation in epidemic control,http://dx.doi.org/10.1038/s41598-019-39714-0,PMC6401305,30837533,CC BY,"For centuries isolation has been the main control strategy of unforeseen epidemic outbreaks. When implemented in full and without delay, isolation is very effective. However, flawless implementation is seldom feasible in practice. We present an epidemic model called SIQ with an isolation protocol, focusing on the consequences of delays and incomplete identification of infected hosts. The continuum limit of this model is a system of Delay Differential Equations, the analysis of which reveals clearly the dependence of epidemic evolution on model parameters including disease reproductive number, isolation probability, speed of identification of infected hosts and recovery rates. Our model offers estimates on minimum response capabilities needed to curb outbreaks, and predictions of endemic states when containment fails. Critical response capability is expressed explicitly in terms of parameters that are easy to obtain, to assist in the evaluation of funding priorities involving preparedness and epidemics management.",2019 Mar 5,"['Young, Lai-Sang', 'Ruschel, Stefan', 'Yanchuk, Serhiy', 'Pereira, Tiago']",Sci Rep,,,True
103497533321c2f879138d46b60ae87cd2fb74cc,PMC,Structural Basis of Nanobodies Targeting the Prototype Norovirus,http://dx.doi.org/10.1128/JVI.02005-18,PMC6401464,30602609,CC BY,"Human norovirus infections are a major disease burden. In this study, we analyzed three new norovirus-specific Nanobodies that interacted with the prototype human norovirus (i.e., genogroup I genotype 1 [GI.1]). We showed that the Nanobodies bound on the side (Nano-7 and Nano-62) and top (Nano-94) of the capsid-protruding (P) domain using X-ray crystallography. Nano-7 and Nano-62 bound at a similar region on the P domain, but the orientations of these two Nanobodies clashed with the shell (S) domain and neighboring P domains on intact particles. This finding suggested that the P domains on the particles should shift in order for Nano-7 and Nano-62 to bind to intact particles. Interestingly, both Nano-7 and Nano-94 were capable of blocking norovirus virus-like particles (VLPs) from binding to histo-blood group antigens (HBGAs), which are important cofactors for norovirus infection. Previously, we showed that the GI.1 HBGA pocket could be blocked with the soluble human milk oligosaccharide 2-fucosyllactose (2′FL). In the current study, we showed that a combined treatment of Nano-7 or Nano-94 with 2′FL enhanced the blocking potential with an additive (Nano-7) or synergistic (Nano-94) effect. We also found that GII Nanobodies with 2′FL also enhanced inhibition. The Nanobody inhibition likely occurred by different mechanisms, including particle aggregation or particle disassembly, whereas 2′FL blocked the HBGA binding site. Overall, these new data showed that the positive effect of the addition of 2′FL was not limited to a single mode of action of Nanobodies or to a single norovirus genogroup. IMPORTANCE The discovery of vulnerable regions on norovirus particles is instrumental in the development of effective inhibitors, particularly for GI noroviruses that are genetically diverse. Analysis of these GI.1-specific Nanobodies has shown that similar to GII norovirus particles, the GI particles have vulnerable regions. The only known cofactor region, the HBGA binding pocket, represents the main target for inhibition. With a combination treatment, i.e., the addition of Nano-7 or Nano-94 with 2′FL, the effect of inhibition was increased. Therefore, combination drug treatments might offer a better approach to combat norovirus infections, especially since the GI genotypes are highly diverse and are continually changing the capsid landscape, and few conserved epitopes have so far been identified.",2019 Mar 5,"['Ruoff, Kerstin', 'Kilic, Turgay', 'Devant, Jessica', 'Koromyslova, Anna', 'Ringel, Alessa', 'Hempelmann, Alexander', 'Geiss, Celina', 'Graf, Juliane', 'Haas, Michelle', 'Roggenbach, Imme', 'Hansman, Grant']",J Virol,,,True
0fe7a393c5db38f3913c46f25a3ed75d14f76900,PMC,"Zika Virus Infection, Basic and Clinical Aspects: A Review Article",,PMC6401583,30847308,CC BY,"BACKGROUND: Zika virus infection has recently attracted the attention of medical community. While clinical manifestations of the infection in adult cases are not severe and disease is not associated with high mortality rates, Zika virus infection can have an impact on fetal development and lead to severe neurodevelopmental abnormalities. METHODS: To gain insight into different aspects of Zika virus infection, a comprehensive literature review was performed. With regard to epidemiology and geographical distribution of Zika virus infection, relevant information was extracted from CDC and WHO websites. RESULTS: In this review, we discuss different basic and clinical aspects of Zika virus infection including virology, epidemiology and pathogenesis of disease. Laboratory methods required for the diagnosis of disease together with ethical issues associated with Zika virus infection will also be discussed in detail. CONCLUSION: Herein, we have tried to provide a multi-faceted view of Zika virus infection, with greater emphasis on disease status in Eastern Mediterranean Region.",2019 Jan,"['NOORBAKHSH, Farshid', 'ABDOLMOHAMMADI, Kamal', 'FATAHI, Yousef', 'DALILI, Hossein', 'RASOOLINEJAD, Mehrnaz', 'REZAEI, Farshid', 'SALEHI-VAZIRI, Mostafa', 'SHAFIEI-JANDAGHI, Nazanin Zahra', 'GOOSHKI, Ehsan Shamsi', 'ZAIM, Morteza', 'NICKNAM, Mohammad Hossein']",Iran J Public Health,,,True
2563d232b59f44a5431f582cdc965b3de048e8dc,PMC,Porcine Hemagglutinating Encephalomyelitis Virus: A Review,http://dx.doi.org/10.3389/fvets.2019.00053,PMC6402421,30873421,CC BY,"The porcine hemagglutinating encephalomyelitis virus (PHEV) is classified as a member of genus Betacoronavirus, family Coronaviridae, sub-family Cornavirinae, and order Nidovirales. PHEV shares the same genomic organization, replication strategy, and expression of viral proteins as other nidoviruses. PHEV produces vomiting and wasting disease (VWD) and/or encephalomyelitis, being the only known neurotropic coronavirus affecting pigs. First clinical outbreak was reported in 1957 in Ontario, Canada. Although pigs are the only species susceptible to natural PHEV infections, the virus displays neurotropism in mice and Wistar rats. Clinical disease, morbidity, and mortality is age-dependent and generally reported only in piglets under 4 weeks old. The primary site of replication of PHEV in pigs is the respiratory tract, and it can be further spread to the central nervous system through the peripheral nervous system via different pathways. The diagnosis of PHEV can be made using a combination of direct and indirect detection methods. The virus can be isolated from different tissues within the acute phase of the clinical signs using primary and secondary pig-derived cell lines. PHEV agglutinates the erythrocytes of mice, rats, chickens, and several other animals. PCR-based methods are useful to identify and subsequently isolate animals that are actively shedding the virus. The ability to detect antibodies allows producers to know the status of first-litter gilts and evaluate their risk of tier offspring to infection. PHEV is highly prevalent and circulates subclinically in most swine herds worldwide. PHEV-related disease is not clinically relevant in most of the swine-producing countries, most likely because of dams are immune to PHEV which may confer passive immunity to their offspring. However, PHEV should be considered a major source of economic loss because of the high mortality on farms with high gilt replacement rates, specific pathogen-free animals, and gnotobiotic swine herds. Thus, in the absence of current PHEV vaccines, promoting virus circulation on farms with early exposure to gilts and young sows could induce maternal immunity and prevent disease in piglets.",2019 Feb 27,"['Mora-Díaz, Juan Carlos', 'Piñeyro, Pablo Enrique', 'Houston, Elizabeth', 'Zimmerman, Jeffrey', 'Giménez-Lirola, Luis Gabriel']",Front Vet Sci,,,True
51a731857c1606428ec1eb47a97a290d2084c460,PMC,Growth enhancement of porcine epidemic diarrhea virus (PEDV) in Vero E6 cells expressing PEDV nucleocapsid protein,http://dx.doi.org/10.1371/journal.pone.0212632,PMC6402621,30840701,CC BY,"More recently emerging strains of porcine epidemic diarrhea virus (PEDV) cause severe diarrhea and especially high mortality rates in infected piglets, leading to substantial economic loss to worldwide swine industry. These outbreaks urgently call for updated and effective PEDV vaccines. Better understanding in PEDV biology and improvement in technological platforms for virus production can immensely assist and accelerate PEDV vaccine development. In this study, we explored the ability of PEDV nucleocapsid (N) protein in improving viral yields in cell culture systems. We demonstrated that PEDV N expression positively affected both recovery of PEDV from infectious clones and PEDV propagation in cell culture. Compared to Vero E6 cells, Vero E6 cells expressing PEDV N could accelerate growth of a slow-growing PEDV strain to higher peak titers by 12 hours or enhance the yield of a vaccine candidate strain by two orders of magnitude. Interestingly, PEDV N also slightly enhances replication of porcine reproductive and respiratory virus, a PEDV relative in the Nidovirales order. These results solidify the importance of N in PEDV recovery and propagation and suggest a potentially useful consideration in designing vaccine production platforms for PEDV or closely related pathogens.",2019 Mar 6,"['Liwnaree, Benjamas', 'Narkpuk, Jaraspim', 'Sungsuwan, Suttipun', 'Jongkaewwattana, Anan', 'Jaru-Ampornpan, Peera']",PLoS One,,,True
850295bc1049a0609b4568610f3b27bf9a150878,PMC,Pneumonia severity index in viral community acquired pneumonia in adults,http://dx.doi.org/10.1371/journal.pone.0210102,PMC6402623,30840626,CC BY,"Pneumonia severity index (PSI) is an important scoring system that can assess the severity of community acquired pneumonia and determine admission status. However, there is a lack of research on whether this scoring system can be applied to viral community acquired pneumonia. The purpose of this study was to evaluate the usefulness of PSI in viral community acquired pneumonia. This retrospective cohort study included 1,434 adult patients (aged ≥18 years) who were admitted to the emergency department of a university hospital during 2013–2015 because of community-acquired pneumonia. Viral infections were diagnosed by multiplex PCR. Patients diagnosed with non-viral community-acquired pneumonia were included in the control group (N = 1,173). The main outcome was 30-day all-cause mortality. multivariate Cox regression analyses were performed to calculate the risk of death. Respiratory viruses were detected in 261 (18.2%) patients with community-acquired pneumonia. Two types of respiratory viruses were detected in 7 cases. Of the 254 cases detected with only one virus, 62 were influenza A, 18 were influenza B, 65 were rhinovirus, 35 were respiratory syncytial virus, 25 were metapneumovirus, 20 were parainfluenza, 17 were coronavirus, 7 were bocavirus, and 5 were adenovirus. Mortality was not significantly different between patients with respiratory virus and those without respiratory virus; the 30-day all-cause mortality rates were 20.3% and 22.4%, respectively (P = 0.45). Mortality rate increased with an increasing PSI score with or without respiratory viral infection. Pulmonary severity index was significantly associated with mortality adjusted for respiratory virus detection (hazard ratio = 1.024, 95% confidence interval = 1.020–1.028). Pneumonia severity index score is an important factor for assessing the prognosis of patients with community-acquired pneumonia, regardless of respiratory virus detection.",2019 Mar 6,"['Kim, Mi-Ae', 'Park, Jae Seok', 'Lee, Choong Won', 'Choi, Won-Il']",PLoS One,,,True
f226ecb8f7484ca7943245de562c6f2f08be80a4,PMC,Phylogeographic investigation of 2014 porcine epidemic diarrhea virus (PEDV) transmission in Taiwan,http://dx.doi.org/10.1371/journal.pone.0213153,PMC6402684,30840679,CC BY,"The porcine epidemic diarrhea virus (PEDV) that emerged and spread throughout Taiwan in 2014 triggered significant concern in the country’s swine industry. Acknowledging the absence of a thorough investigation at the geographic level, we used 2014 outbreak sequence information from the Taiwan government’s open access databases plus GenBank records to analyze PEDV dissemination among Taiwanese pig farms. Genetic sequences, locations, and dates of identified PEDV-positive cases were used to assess spatial, temporal, clustering, GIS, and phylogeographic factors affecting PEDV dissemination. Our conclusion is that S gene sequences from 2014 PEDV-positive clinical samples collected in Taiwan were part of the same Genogroup 2 identified in the US in 2013. According to phylogenetic and phylogeographic data, viral strains collected in different areas were generally independent of each other, with certain clusters identified across different communities. Data from GIS and multiple potential infection factors were used to pinpoint cluster dissemination in areas with large numbers of swine farms in southern Taiwan. The data indicate that the 2014 Taiwan PEDV epidemic resulted from the spread of multiple strains, with strong correlations identified with pig farm numbers and sizes (measured as animal concentrations), feed mill numbers, and the number of slaughterhouses in a specifically defined geographic area.",2019 Mar 6,"['Sung, Ming-Hua', 'Lin, Chao-Nan', 'Chiou, Ming-Tang', 'Cheng, I-Ju', 'Thanh, Quang-Hien', 'Chao, Day-Yu', 'Lan, Yu-Ching']",PLoS One,,,True
e545cfc731b5511fe89ef69e6d09cbc9bf428704,PMC,Bacillus Calmette-Guérin Induces PD-L1 Expression on Antigen-Presenting Cells via Autocrine and Paracrine Interleukin-STAT3 Circuits,http://dx.doi.org/10.1038/s41598-019-40145-0,PMC6403281,30842561,CC BY,"Bacillus Calmette-Guérin (BCG) is the only licensed vaccine for tuberculosis (TB), and is also used as an immunotherapy for bladder cancer and other malignancies due to its immunostimulatory properties. Mycobacteria spp., however, are well known for their numerous immune evasion mechanisms that limit the true potential of their therapeutic use. One such major mechanism is the induction of programmed death ligand-1 (PD-L1), which mitigates adaptive immune responses. Here, we sought to unravel the molecular pathways behind PD-L1 up-regulation on antigen-presenting cells (APCs) by BCG. We found that infection of APCs with BCG induced PD-L1 up-regulation, but that this did not depend on direct infection, suggesting a soluble mediator for this effect. BCG induced potent quantities of IL-6 and IL-10, and the downstream transcription factor STAT3 was hyper-phosphorylated. Intracellular analyses revealed that levels of PD-L1 molecules were associated with the STAT3 phosphorylation state, suggesting a causal link. Neutralisation of the IL-6 or IL-10 cytokine receptors dampened STAT3 phosphorylation and BCG-mediated up-regulation of PD-L1 on APCs. Pharmacological inhibition of STAT3 achieved the same effect, confirming an autocrine-paracrine cytokine loop as a mechanism for BCG-mediated up-regulation of PD-L1. Finally, an in vivo immunisation model showed that BCG vaccination under PD-L1 blockade could enhance antigen-specific memory CD4 T-cell responses. These novel findings could lead to refinement of BCG as both a vaccine for infectious disease and as a cancer immunotherapy.",2019 Mar 6,"['Copland, Alastair', 'Sparrow, Adam', 'Hart, Peter', 'Diogo, Gil Reynolds', 'Paul, Mathew', 'Azuma, Miyuki', 'Reljic, Rajko']",Sci Rep,,,True
4ffacbedf65fc0a9fe529e94b43fc3e9018775f6,PMC,A colorimetric strategy based on dynamic chemistry for direct detection of Trypanosomatid species,http://dx.doi.org/10.1038/s41598-019-39946-0,PMC6403333,30842455,CC BY,"Leishmaniasis and Chagas disease are endemic in many countries, and re-emerging in the developed countries. A rapid and accurate diagnosis is important for early treatment for reducing the duration of infection as well as for preventing further potential health complications. In this work, we have developed a novel colorimetric molecular assay that integrates nucleic acid analysis by dynamic chemistry (ChemNAT) with reverse dot-blot hybridization in an array format for a rapid and easy discrimination of Leishmania major and Trypanosoma cruzi. The assay consists of a singleplex PCR step that amplifies a highly homologous DNA sequence which encodes for the RNA component of the large ribosome subunit. The amplicons of the two different parasites differ between them by single nucleotide variations, known as “Single Nucleotide Fingerprint” (SNF) markers. The SNF markers can be easily identified by naked eye using a novel micro Spin-Tube device ""Spin-Tube"", as each of them creates a specific spot pattern. Moreover, the direct use of ribosomal RNA without requiring the PCR pre-amplification step is also feasible, further increasing the simplicity of the assay. The molecular assay delivers sensitivity capable of identifying up to 8.7 copies per µL with single mismatch specificity. The Spin-Tube thus represents an innovative solution providing benefits in terms of time, cost, and simplicity, all of which are crucial for the diagnosis of infectious disease in developing countries.",2019 Mar 6,"['Tabraue-Chávez, Mavys', 'Luque-González, María Angélica', 'Marín-Romero, Antonio', 'Sánchez-Martín, Rosario María', 'Escobedo-Araque, Pablo', 'Pernagallo, Salvatore', 'Díaz-Mochón, Juan José']",Sci Rep,,,True
ffe762a0c68996c65336d3782728238d24658b0e,PMC,Alignment-free method for DNA sequence clustering using Fuzzy integral similarity,http://dx.doi.org/10.1038/s41598-019-40452-6,PMC6403383,30842590,CC BY,"A larger amount of sequence data in private and public databases produced by next-generation sequencing put new challenges due to limitation associated with the alignment-based method for sequence comparison. So, there is a high need for faster sequence analysis algorithms. In this study, we developed an alignment-free algorithm for faster sequence analysis. The novelty of our approach is the inclusion of fuzzy integral with Markov chain for sequence analysis in the alignment-free model. The method estimate the parameters of a Markov chain by considering the frequencies of occurrence of all possible nucleotide pairs from each DNA sequence. These estimated Markov chain parameters were used to calculate similarity among all pairwise combinations of DNA sequences based on a fuzzy integral algorithm. This matrix is used as an input for the neighbor program in the PHYLIP package for phylogenetic tree construction. Our method was tested on eight benchmark datasets and on in-house generated datasets (18 s rDNA sequences from 11 arbuscular mycorrhizal fungi (AMF) and 16 s rDNA sequences of 40 bacterial isolates from plant interior). The results indicate that the fuzzy integral algorithm is an efficient and feasible alignment-free method for sequence analysis on the genomic scale.",2019 Mar 6,"['Saw, Ajay Kumar', 'Raj, Garima', 'Das, Manashi', 'Talukdar, Narayan Chandra', 'Tripathy, Binod Chandra', 'Nandi, Soumyadeep']",Sci Rep,,,False
30d216d33a2ead14fe0230f40fd76f6ae2d3b79c,PMC,Alignment-free method for DNA sequence clustering using Fuzzy integral similarity,http://dx.doi.org/10.1038/s41598-019-40452-6,PMC6403383,30842590,CC BY,"A larger amount of sequence data in private and public databases produced by next-generation sequencing put new challenges due to limitation associated with the alignment-based method for sequence comparison. So, there is a high need for faster sequence analysis algorithms. In this study, we developed an alignment-free algorithm for faster sequence analysis. The novelty of our approach is the inclusion of fuzzy integral with Markov chain for sequence analysis in the alignment-free model. The method estimate the parameters of a Markov chain by considering the frequencies of occurrence of all possible nucleotide pairs from each DNA sequence. These estimated Markov chain parameters were used to calculate similarity among all pairwise combinations of DNA sequences based on a fuzzy integral algorithm. This matrix is used as an input for the neighbor program in the PHYLIP package for phylogenetic tree construction. Our method was tested on eight benchmark datasets and on in-house generated datasets (18 s rDNA sequences from 11 arbuscular mycorrhizal fungi (AMF) and 16 s rDNA sequences of 40 bacterial isolates from plant interior). The results indicate that the fuzzy integral algorithm is an efficient and feasible alignment-free method for sequence analysis on the genomic scale.",2019 Mar 6,"['Saw, Ajay Kumar', 'Raj, Garima', 'Das, Manashi', 'Talukdar, Narayan Chandra', 'Tripathy, Binod Chandra', 'Nandi, Soumyadeep']",Sci Rep,,,True
cdf5579d820bb3154dc31e2d72bce2fe3f39b1bf,PMC,Alignment-free method for DNA sequence clustering using Fuzzy integral similarity,http://dx.doi.org/10.1038/s41598-019-40452-6,PMC6403383,30842590,CC BY,"A larger amount of sequence data in private and public databases produced by next-generation sequencing put new challenges due to limitation associated with the alignment-based method for sequence comparison. So, there is a high need for faster sequence analysis algorithms. In this study, we developed an alignment-free algorithm for faster sequence analysis. The novelty of our approach is the inclusion of fuzzy integral with Markov chain for sequence analysis in the alignment-free model. The method estimate the parameters of a Markov chain by considering the frequencies of occurrence of all possible nucleotide pairs from each DNA sequence. These estimated Markov chain parameters were used to calculate similarity among all pairwise combinations of DNA sequences based on a fuzzy integral algorithm. This matrix is used as an input for the neighbor program in the PHYLIP package for phylogenetic tree construction. Our method was tested on eight benchmark datasets and on in-house generated datasets (18 s rDNA sequences from 11 arbuscular mycorrhizal fungi (AMF) and 16 s rDNA sequences of 40 bacterial isolates from plant interior). The results indicate that the fuzzy integral algorithm is an efficient and feasible alignment-free method for sequence analysis on the genomic scale.",2019 Mar 6,"['Saw, Ajay Kumar', 'Raj, Garima', 'Das, Manashi', 'Talukdar, Narayan Chandra', 'Tripathy, Binod Chandra', 'Nandi, Soumyadeep']",Sci Rep,,,True
fba40688b8d7ceae8fdfde3b39a30e042219704b,PMC,Alignment-free method for DNA sequence clustering using Fuzzy integral similarity,http://dx.doi.org/10.1038/s41598-019-40452-6,PMC6403383,30842590,CC BY,"A larger amount of sequence data in private and public databases produced by next-generation sequencing put new challenges due to limitation associated with the alignment-based method for sequence comparison. So, there is a high need for faster sequence analysis algorithms. In this study, we developed an alignment-free algorithm for faster sequence analysis. The novelty of our approach is the inclusion of fuzzy integral with Markov chain for sequence analysis in the alignment-free model. The method estimate the parameters of a Markov chain by considering the frequencies of occurrence of all possible nucleotide pairs from each DNA sequence. These estimated Markov chain parameters were used to calculate similarity among all pairwise combinations of DNA sequences based on a fuzzy integral algorithm. This matrix is used as an input for the neighbor program in the PHYLIP package for phylogenetic tree construction. Our method was tested on eight benchmark datasets and on in-house generated datasets (18 s rDNA sequences from 11 arbuscular mycorrhizal fungi (AMF) and 16 s rDNA sequences of 40 bacterial isolates from plant interior). The results indicate that the fuzzy integral algorithm is an efficient and feasible alignment-free method for sequence analysis on the genomic scale.",2019 Mar 6,"['Saw, Ajay Kumar', 'Raj, Garima', 'Das, Manashi', 'Talukdar, Narayan Chandra', 'Tripathy, Binod Chandra', 'Nandi, Soumyadeep']",Sci Rep,,,False
ad0d3c262412a85fc363d0d3aa42f2485c73a2b9,PMC,Alignment-free method for DNA sequence clustering using Fuzzy integral similarity,http://dx.doi.org/10.1038/s41598-019-40452-6,PMC6403383,30842590,CC BY,"A larger amount of sequence data in private and public databases produced by next-generation sequencing put new challenges due to limitation associated with the alignment-based method for sequence comparison. So, there is a high need for faster sequence analysis algorithms. In this study, we developed an alignment-free algorithm for faster sequence analysis. The novelty of our approach is the inclusion of fuzzy integral with Markov chain for sequence analysis in the alignment-free model. The method estimate the parameters of a Markov chain by considering the frequencies of occurrence of all possible nucleotide pairs from each DNA sequence. These estimated Markov chain parameters were used to calculate similarity among all pairwise combinations of DNA sequences based on a fuzzy integral algorithm. This matrix is used as an input for the neighbor program in the PHYLIP package for phylogenetic tree construction. Our method was tested on eight benchmark datasets and on in-house generated datasets (18 s rDNA sequences from 11 arbuscular mycorrhizal fungi (AMF) and 16 s rDNA sequences of 40 bacterial isolates from plant interior). The results indicate that the fuzzy integral algorithm is an efficient and feasible alignment-free method for sequence analysis on the genomic scale.",2019 Mar 6,"['Saw, Ajay Kumar', 'Raj, Garima', 'Das, Manashi', 'Talukdar, Narayan Chandra', 'Tripathy, Binod Chandra', 'Nandi, Soumyadeep']",Sci Rep,,,True
70da3ee5739197acb1879c1d23606681aaac2e1c,PMC,A balanced game: chicken macrophage response to ALV-J infection,http://dx.doi.org/10.1186/s13567-019-0638-y,PMC6404279,30841905,CC BY,"Avian leukosis virus subgroup J (ALV-J) infection can cause tumors and immunosuppression in infected chickens. Macrophages play a central role in host defense against invading pathogens. In this study, we discovered an interesting phenomenon: ALV-J replication is weakened from 3 hours post-infection (hpi) to 36 hpi, which was verified using Western blotting and RT-PCR. To further investigate the interaction between ALV-J and macrophages, transcriptome analysis was performed to analyze the host genes’ function in chicken primary monocyte-derived macrophages (MDM). Compared to the uninfected control, 624 up-regulated differentially expressed genes (DEG) and 341 down-regulated DEG at 3 hpi, and 174 up-regulated DEG and 87 down-regulated DEG at 36 hpi were identified in chicken MDM, respectively. ALV-J infection induced strong innate immune responses in chicken MDM at 3 hpi, instead of 36 hpi, according to the analysis results of Gene Ontology and KEGG pathway. Importantly, the host factors, such as up-regulated MIP-3α, IL-1β, iNOS, K60, IRG1, CH25H, NFKBIZ, lysozyme and OASL were involved in the host defense response during the course of ALV-J infection. On the contrary, up-regulated EX-FABP, IL4I1, COX-2, NFKBIA, TNFAIP3 and the Jak STAT pathway inhibitors including CISH, SOCS1 and SOCS3 are beneficial to ALV-J survival in chicken macrophages. We speculated that ALV-J tropism for macrophages helps to establish a latent infection in chicken MDM from 6 to 36 hpi. The present study provides a comprehensive view of the interactions between macrophages and ALV-J. It suggests the mechanisms of defense of chicken macrophages against ALV-J invasion and how ALV-J escape the host innate immune responses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13567-019-0638-y) contains supplementary material, which is available to authorized users.",2019 Mar 6,"['Feng, Min', 'Xie, Tingting', 'Li, Yuanfang', 'Zhang, Nan', 'Lu, Qiuyuan', 'Zhou, Yaohong', 'Shi, Meiqing', 'Sun, Jingchen', 'Zhang, Xiquan']",Vet Res,,,True
d1312034ff2df8c47731d9519e2a4330e5cbc535,PMC,"Pertussis: The Identify, Isolate, Inform Tool Applied to a Re-emerging Respiratory Illness",http://dx.doi.org/10.5811/westjem.2018.11.40023,PMC6404696,30881535,CC BY,"Pertussis, commonly referred to as “whooping cough,” is a highly contagious acute respiratory infection that has exhibited cyclical outbreaks throughout the last century. Although vaccines have provided some immunity, many populations, including infants and pregnant women, remain at risk for serious illness. Through the use of the novel “Identify, Isolate, Inform” (3I) tool, emergency department (ED) providers can readily recognize key symptoms of the disease and risk factors for exposure, thus curbing its transmission through early initiation of antimicrobial therapy and post-exposure prophylaxis. The three classic stages of pertussis include an initial catarrhal stage, characterized by nonspecific upper respiratory infection symptoms, which may advance to the paroxysmal stage, revealing the distinctive “whooping cough.” This cough can persist for weeks to months leading into the convalescent stage. Household contacts of patients with suspected pertussis or other asymptomatic, high-risk populations (infants, pregnant women in their third trimester, and childcare workers) may benefit from post-exposure prophylactic therapy. The Pertussis 3I tool can also alert healthcare professionals to the proper respiratory droplet precautions during contact with a symptomatic patient, as well as isolation practices until antimicrobial treatment is in progress. ED personnel should then inform local public health departments of any suspected cases. All of these actions will ultimately aid public health in controlling the incidence of pertussis cases, thus ensuring the protection of the general public from this re-emerging respiratory illness.",2019 Mar 5,"['Koenig, Kristi L.', 'Farah, Jennifer', 'McDonald, Eric C.', 'Thihalolipavan, Sayone', 'Burns, Michael J.']",West J Emerg Med,,,True
4bcf7c070cff74e01013527a1957c676487d98d0,PMC,Antibody-Dependent Cellular Phagocytosis in Antiviral Immune Responses,http://dx.doi.org/10.3389/fimmu.2019.00332,PMC6404786,30873178,CC BY,"Antiviral activities of antibodies may either be dependent only on interactions between the antibody and cognate antigen, as in binding and neutralization of an infectious virion, or instead may require interactions between antibody–antigen immune complexes and immunoproteins or Fc receptor expressing immune effector cells. These Fc receptor-dependent antibody functions provide a direct link between the innate and adaptive immune systems by combining the potent antiviral activity of innate effector cells with the diversity and specificity of the adaptive humoral response. The Fc receptor-dependent function of antibody-dependent cellular phagocytosis (ADCP) provides mechanisms for clearance of virus and virus-infected cells, as well as for stimulation of downstream adaptive immune responses by facilitating antigen presentation, or by stimulating the secretion of inflammatory mediators. In this review, we discuss the properties of Fc receptors, antibodies, and effector cells that influence ADCP. We also provide and interpret evidence from studies that support a potential role for ADCP in either inhibiting or enhancing viral infection. Finally, we describe current approaches used to measure antiviral ADCP and discuss considerations for the translation of studies performed in animal models. We propose that additional investigation into the role of ADCP in protective viral responses, the specific virus epitopes targeted by ADCP antibodies, and the types of phagocytes and Fc receptors involved in ADCP at sites of virus infection will provide insight into strategies to successfully leverage this important immune response for improved antiviral immunity through rational vaccine design.",2019 Feb 28,"['Tay, Matthew Zirui', 'Wiehe, Kevin', 'Pollara, Justin']",Front Immunol,,,True
6885e0e09ec18e5a9ec6e40efb3645824f25fe79,PMC,"Projections of Ebola outbreak size and duration with and without vaccine use in Équateur, Democratic Republic of Congo, as of May 27, 2018",http://dx.doi.org/10.1371/journal.pone.0213190,PMC6405095,30845236,CC BY,"As of May 27, 2018, 6 suspected, 13 probable and 35 confirmed cases of Ebola virus disease (EVD) had been reported in Équateur Province, Democratic Republic of Congo. We used reported case counts and time series from prior outbreaks to estimate the total outbreak size and duration with and without vaccine use. We modeled Ebola virus transmission using a stochastic branching process model that included reproduction numbers from past Ebola outbreaks and a particle filtering method to generate a probabilistic projection of the outbreak size and duration conditioned on its reported trajectory to date; modeled using high (62%), low (44%), and zero (0%) estimates of vaccination coverage (after deployment). Additionally, we used the time series for 18 prior Ebola outbreaks from 1976 to 2016 to parameterize the Thiel-Sen regression model predicting the outbreak size from the number of observed cases from April 4 to May 27. We used these techniques on probable and confirmed case counts with and without inclusion of suspected cases. Probabilistic projections were scored against the actual outbreak size of 54 EVD cases, using a log-likelihood score. With the stochastic model, using high, low, and zero estimates of vaccination coverage, the median outbreak sizes for probable and confirmed cases were 82 cases (95% prediction interval [PI]: 55, 156), 104 cases (95% PI: 58, 271), and 213 cases (95% PI: 64, 1450), respectively. With the Thiel-Sen regression model, the median outbreak size was estimated to be 65.0 probable and confirmed cases (95% PI: 48.8, 119.7). Among our three mathematical models, the stochastic model with suspected cases and high vaccine coverage predicted total outbreak sizes closest to the true outcome. Relatively simple mathematical models updated in real time may inform outbreak response teams with projections of total outbreak size and duration.",2019 Mar 7,"['Kelly, J. Daniel', 'Worden, Lee', 'Wannier, S. Rae', 'Hoff, Nicole A.', 'Mukadi, Patrick', 'Sinai, Cyrus', 'Ackley, Sarah', 'Chen, Xianyun', 'Gao, Daozhou', 'Selo, Bernice', 'Mossoko, Mathais', 'Okitolonda-Wemakoy, Emile', 'Richardson, Eugene T.', 'Rutherford, George W.', 'Lietman, Thomas M.', 'Muyembe-Tamfum, Jean Jacques', 'Rimoin, Anne W.', 'Porco, Travis C.']",PLoS One,,,True
b2a382ff964250dde3c7387b87bd244b27e4f81d,PMC,Distinct transcriptional modules in the peripheral blood mononuclear cells response to human respiratory syncytial virus or to human rhinovirus in hospitalized infants with bronchiolitis,http://dx.doi.org/10.1371/journal.pone.0213501,PMC6405118,30845274,CC BY,"Human respiratory syncytial virus (HRSV) is the main cause of bronchiolitis during the first year of life, when infections by other viruses, such as rhinovirus, also occur and are clinically indistinguishable from those caused by HRSV. In hospitalized infants with bronchiolitis, the analysis of gene expression profiles from peripheral blood mononuclear cells (PBMC) may be useful for the rapid identification of etiological factors, as well as for developing diagnostic tests, and elucidating pathogenic mechanisms triggered by different viral agents. In this study we conducted a comparative global gene expression analysis of PBMC obtained from two groups of infants with acute viral bronchiolitis who were infected by HRSV (HRSV group) or by HRV (HRV group). We employed a weighted gene co-expression network analysis (WGCNA) which allows the identification of transcriptional modules and their correlations with HRSV or HRV groups. This approach permitted the identification of distinct transcription modules for the HRSV and HRV groups. According to these data, the immune response to HRSV infection—comparatively to HRV infection—was more associated to the activation of the interferon gamma signaling pathways and less related to neutrophil activation mechanisms. Moreover, we also identified host-response molecular markers that could be used for etiopathogenic diagnosis. These results may contribute to the development of new tests for respiratory virus identification. The finding that distinct transcriptional profiles are associated to specific host responses to HRSV or to HRV may also contribute to the elucidation of the pathogenic mechanisms triggered by different respiratory viruses, paving the way for new therapeutic strategies.",2019 Mar 7,"['Vieira, Sandra E.', 'Bando, Silvia Y.', 'de Paulis, Milena', 'Oliveira, Danielle B. L.', 'Thomazelli, Luciano M.', 'Durigon, Edison L.', 'Martinez, Marina B.', 'Moreira-Filho, Carlos Alberto']",PLoS One,,,True
db0c5eb977ace3792bd9796c78e4d7e6bc243a7e,PMC,The association between low glucose-6-phosphate dehydrogenase activity level and hepatitis B virus infection among pre-pregnant reproductive-age Chinese females,http://dx.doi.org/10.1038/s41598-019-40354-7,PMC6405931,30846733,CC BY,"The relationship between females with low glucose-6-phosphate dehydrogenase activity level (LG6PD) and HBV infection is unclear. We conducted a cross sectional study of 124 406 reproductive-age Chinese females who participated in the National Free Pre-conception Check-up Projects to investigate the risk of HBV infection among females with LG6PD and its effect on liver enzyme. Based on HBV serological test results, the participants were divided into the susceptible, immunized, and HBV infected groups. The multivariable-adjusted odds ratios (ORs) for HBV infection in LG6PD participants were 1.71 (95% confidence interval (CI): 1.45–2.01) and 1.41 (95% CI: 1.23–1.62), respectively with the susceptible and immunized participants as references, compared to those without LG6PD. Participants with HBV infection only and combined with HBV infection and LG6PD had 184% and 249% significantly higher risks of elevated alanine transaminase (ALT) (susceptible participants as reference). If the immunized participants were used as reference, significant higher odds of elevated ALT occurred (3.48 (95% CI: 3.18–3.80), 4.28 (95% CI: 2.92–6.28)). Thus, reproductive-age females with LG6PD had a higher prevalence of HBV infection, and LG6PD might exacerbate ALT elevation in HBV infected females. Our findings underscore the need to explore collaborative management approaches for these two diseases among reproductive-age females for maternal and child health.",2019 Mar 7,"['Zhao, Jun', 'Zhang, Xu', 'Guan, Ting', 'Dai, Qiaoyun', 'He, Wenshan', 'Zhang, Hongguang', 'Wang, Yuanyuan', 'Wang, Bei', 'Peng, Zuoqi', 'Hu, Xuhuai', 'Qi, Daxun', 'Yang, Xueying', 'Zhang, Yue', 'Ma, Xu']",Sci Rep,,,True
b3ecc8a7254be2774d6b64e0793dd38b035ad7bd,PMC,"Complete Genome Sequences of Two Porcine Deltacoronavirus Strains from Henan Province, China",http://dx.doi.org/10.1128/MRA.01517-18,PMC6406112,30863822,CC BY,"In 2016 and 2018, two porcine deltacoronavirus (PDCoV) strains, CH-01 and HNZK-02, were identified from fecal samples of piglets with diarrhea in Henan Province, China. The full-length genomic sequence analysis indicated that these two strains had high nucleotide identities with the other Chinese PDCoV epidemic strains.",2019 Mar 7,"['Liang, Qingqing', 'Li, Bingxiao', 'Zhang, Honglei', 'Hu, Hui']",Microbiol Resour Announc,,,True
2f724b7cfad10b8e35297cd8f000b88f67939d72,PMC,First Complete Genome Sequence of a Feline Alphacoronavirus 1 Strain from Brazil,http://dx.doi.org/10.1128/MRA.01535-18,PMC6406114,30863824,CC BY,"We identified a strain of Alphacoronavirus 1, FCoV-SB22, from a pool of fecal samples from domestic cats from a rural settlement in the municipality of Santa Bárbara, Pará, Brazil. The nucleotide identity with feline coronavirus was 91.5%. The present study reports the first complete genome sequence of a feline coronavirus from Brazil.",2019 Mar 7,"['de Barros, Bruno de Cássio Veloso', 'de Castro, Ceyla Maria Oeiras', 'Pereira, Diego', 'Ribeiro, Laila Graziela', 'Júnior, José Wandilson Barboza Duarte', 'Casseb, Samir Mansour Moraes', 'Holanda, Gustavo Moraes', 'Cruz, Ana Cecília Ribeiro', 'Júnior, Edivaldo Costa Sousa', 'Mascarenhas, Joana D’Arc Pereira']",Microbiol Resour Announc,,,True
da2bc204c003c35a7edb72cd61a721d51392f1da,PMC,Modulation of Autophagy for Controlling Immunity,http://dx.doi.org/10.3390/cells8020138,PMC6406335,30744138,CC BY,"Autophagy is an essential process that maintains physiological homeostasis by promoting the transfer of cytoplasmic constituents to autophagolysosomes for degradation. In immune cells, the autophagy pathway plays an additional role in facilitating proper immunological functions. Specifically, the autophagy pathway can participate in controlling key steps in innate and adaptive immunity. Accordingly, alterations in autophagy have been linked to inflammatory diseases and defective immune responses against pathogens. In this review, we discuss the various roles of autophagy signaling in coordinating immune responses and how these activities are connected to pathological conditions. We highlight the therapeutic potential of autophagy modulators that can impact immune responses and the mechanisms of action responsible.",2019 Feb 9,"['Jang, Young Jin', 'Kim, Jae Hwan', 'Byun, Sanguine']",Cells,,,True
7ed9ceed11e8adac9aca2e5e53e8f863b6a2c42a,PMC,Spatio-Temporal Analysis of Infectious Diseases,http://dx.doi.org/10.3390/ijerph16040669,PMC6406380,30823539,CC BY,,2019 Feb 25,"López-Quílez, Antonio",Int J Environ Res Public Health,,,True
e8815ab60a5c49b74ba06d648c5e7c89c50668c0,PMC,Emerging Influenza D Virus Threat: What We Know so Far!,http://dx.doi.org/10.3390/jcm8020192,PMC6406440,30764577,CC BY,"Influenza viruses, since time immemorial, have been the major respiratory pathogen known to infect a wide variety of animals, birds and reptiles with established lineages. They belong to the family Orthomyxoviridae and cause acute respiratory illness often during local outbreaks or seasonal epidemics and occasionally during pandemics. Recent studies have identified a new genus within the Orthomyxoviridae family. This newly identified pathogen, D/swine/Oklahoma/1334/2011 (D/OK), first identified in pigs with influenza-like illness was classified as the influenza D virus (IDV) which is distantly related to the previously characterized human influenza C virus. Several other back-to-back studies soon suggested cattle as the natural reservoir and possible involvement of IDV in the bovine respiratory disease complex was established. Not much is known about its likelihood to cause disease in humans, but it definitely poses a potential threat as an emerging pathogen in cattle-workers. Here, we review the evolution, epidemiology, virology and pathobiology of influenza D virus and the possibility of transmission among various hosts and potential to cause human disease.",2019 Feb 5,"['Asha, Kumari', 'Kumar, Binod']",J Clin Med,,,True
5eb20deb48c231973cf0a796ca1c6898cbf2d07d,PMC,Design and Validation with Influenza A Virus of an Aerosol Transmission Chamber for Ferrets,http://dx.doi.org/10.3390/ijerph16040609,PMC6406687,30791478,CC BY,"Background: The importance of aerosols in the spread of viruses like influenza is still a subject of debate. Indeed, most viruses can also be transmitted through direct contact and droplets. Therefore, the importance of the airborne route in a clinical context is difficult to determine. The aim of this study was to design a chamber system to study the airborne transmission of viruses between ferrets. Methods: A system composed of three chambers connected in series, each one housing one ferret and preventing direct contact, was designed. The chambers were designed to house the ferrets for several days and to study the transmission of viruses from an infected (index) ferret to two naïve ferrets via aerosols and droplets or aerosols only. A particle separator was designed that can be used to modulate the size of the particles traveling between the chambers. The chamber system was validated using standard dust as well as with ferrets infected with influenza A virus. Conclusions: The 50% efficiency cut-off of the separator could be modulated between a 5-µm and an 8-µm aerodynamic diameter. In the described setup, influenza A virus was transmitted through the aerosol route in two out of three experiments, and through aerosols and droplets in all three experiments.",2019 Feb 19,"['Turgeon, Nathalie', 'Hamelin, Marie-Ève', 'Verreault, Daniel', 'Lévesque, Ariane', 'Rhéaume, Chantal', 'Carbonneau, Julie', 'Checkmahomed, Liva', 'Girard, Matthieu', 'Boivin, Guy', 'Duchaine, Caroline']",Int J Environ Res Public Health,,,True
7dbe0bb2d5bfc8c90c1a0185c6ea608452b08276,PMC,Feather Pecking and Cannibalism in Non-Beak-Trimmed Laying Hen Flocks—Farmers’ Perspectives,http://dx.doi.org/10.3390/ani9020043,PMC6406704,30704113,CC BY,"SIMPLE SUMMARY: Pecking-related problems are common in intensive egg production, diminishing hen welfare and production performance, and negatively affecting sustainability. Beak trimming is a common practice to control these problems, but in Finland beak trimming is prohibited. Finnish egg producers have decades-long experience of egg production with intact-beaked hens. This experience, and their management of pecking-related problems, could benefit producers in other countries. The online questionnaire aimed to gather information about Finnish farmers’ attitudes towards beak trimming, their estimation of the seriousness of pecking problems in their laying hen flocks, common risk factors and the best practices to prevent attendant problems. The questionnaire received 35 responses. Finnish egg producers appeared strongly to support a policy of not trimming beaks. Motivation against beak trimming was explained by considering it to be unnecessary and unethical. Most respondents did not regard pecking-related problems as being very severe in their flocks. Lighting, feeding and flock management problems represented the most important risk factors regarding pecking problems. Generally, the same topics were highlighted as being the most important intervention measures for managing an on-going pecking problem. The study indicates that it is possible to incorporate a non-beak-trimming policy as a component of sustainable egg production. ABSTRACT: Pecking-related problems are common in intensive egg production, compromising hen welfare, causing farmers economic losses and negatively affecting sustainability. These problems are often controlled by beak trimming, which in Finland is prohibited. An online questionnaire aimed to collect information from farmers about pecking-related problems in Finnish laying hen flocks, important risk factors and the best experiences to prevent the problems. Additionally, the farmers’ attitudes towards beak trimming were examined. We received 35 responses, which represents about 13% of all Finnish laying hen farms with ≥300 laying hens. The majority of respondents stated that a maximum of 5–7% incidence of feather pecking or 1–2% incidence of cannibalism would be tolerable. The majority of respondents (74%) expressed that they would definitely not use beak-trimmed hens. Only two respondents indicated that they would probably use beak-trimmed hens were the practice permitted. Among risk factors, light intensity earned the highest mean (6.3), on a scale from 1 (not important) to 7 (extremely important). Other important problems included those that occurred during rearing, feeding, flock management and problems with drinking water equipment (mean 5.9, each). The most important intervention measures included optimal lighting and feeding, flock management, and removing the pecker and victim. Concluding, Finnish farmers had strong negative attitudes towards beak trimming. The study underlines the importance of flock management, especially lighting and feeding, in preventing pecking problems and indicates that it is possible to incorporate a non-beak-trimming policy into sustainable egg production.",2019 Jan 30,"['Kaukonen, Eija', 'Valros, Anna']",Animals (Basel),,,True
2ca680635b3f3dcf21ea32eca2ef05b3ef44d3ec,PMC,Rodents Versus Pig Model for Assessing the Performance of Serotype Chimeric Ad5/3 Oncolytic Adenoviruses,http://dx.doi.org/10.3390/cancers11020198,PMC6406826,30744019,CC BY,"Oncolytic adenoviruses (Ad) are promising tools for cancer therapeutics. Most Ad-based therapies utilize species C serotypes, with Adenovirus type 5 (Ad5) most commonly employed. Prior clinical trials demonstrated low efficiency of oncolytic Ad5 vectors, mainly due to the absence of Ad5 primary receptor (Coxsackie and Adenovirus Receptor, CAR) on cancer cells. Engineering serotype chimeric vectors (Ad5/3) to utilize Adenovirus type 3 (Ad3) receptors has greatly improved their oncolytic potential. Clinical translation of these infectivity-enhanced vectors has been challenging due to a lack of replication permissive animal models. In this study, we explored pigs as a model to study the performance of fiber-modified Ad5/3 chimeric vectors. As a control, the Ad5 fiber-unmodified virus was used. We analyzed binding, gene transfer, replication, and cytolytic ability of Ad5 and Ad5/3 in various non-human cell lines (murine, hamster, canine, porcine). Among all tested cell lines only porcine cells supported active binding and replication of Ad5/3. Syrian hamster cells supported Ad5 replication but showed no evidence of productive viral replication after infection with Ad5/3 vectors. Transduction and replication ability of Ad5/3 in porcine cells outperformed Ad5, a phenomenon often observed in human cancer cell lines. Replication of Ad5 and Ad5/3 was subsequently evaluated in vivo in immunocompetent pigs. Quantitative PCR analyses 7 days post infection revealed Ad5 and Ad5/3 DNA and replication-dependent luciferase activity in the swine lungs and spleen indicating active replication in these tissues. These studies demonstrated the flaws in using Syrian hamsters for testing serotype chimeric Ad5/3 vectors. This is the first report to validate the pig as a valuable model for preclinical testing of oncolytic adenoviruses utilizing Adenovirus type 3 receptors. We hope that these data will help to foster the clinical translation of oncolytic adenoviruses including those with Ad3 retargeted tropism.",2019 Feb 8,"['Koodie, Lisa', 'Robertson, Matthew G.', 'Chandrashekar, Malavika', 'Ruth, George', 'Dunning, Michele', 'Bianco, Richard W.', 'Davydova, Julia']",Cancers (Basel),,,True
615c4a00d39f88f880ce3677ed76771c499ff652,PMC,Diagnostic tests for Crimean-Congo haemorrhagic fever: a widespread tickborne disease,http://dx.doi.org/10.1136/bmjgh-2018-001114,PMC6407549,30899574,CC BY,"Crimean-Congo haemorrhagic fever (CCHF) is a widespread tickborne disease that circulates in wild and domestic animal hosts, and causes severe and often fatal haemorrhagic fever in infected humans. Due to the lack of treatment options or vaccines, and a high fatality rate, CCHF virus (CCHFV) is considered a high-priority pathogen according to the WHO R&D Blueprint. Several commercial reverse transcriptase PCR (RT-PCR) and serological diagnostic assays for CCHFV are already available, including febrile agent panels to distinguish CCHFV from other viral haemorrhagic fever agents; however, the majority of international laboratories use inhouse assays. As CCHFV has numerous amplifying animal hosts, a cross-sectoral ‘One Health’ approach to outbreak prevention is recommended to enhance notifications and enable early warning for genetic and epidemiological shifts in the human, animal and tick populations. However, a lack of guidance for surveillance in animals, harmonisation of case identification and validated serodiagnostic kits for animal testing hinders efforts to strengthen surveillance systems. Additionally, as RT-PCR tests tend to be lineage-specific for regional circulating strains, there is a need for pan-lineage sensitive diagnostics. Adaptation of existing tests to point-of-care molecular diagnostic platforms that can be implemented in clinic or field-based settings would be of value given the potential for CCHFV outbreaks in remote or low-resource areas. Finally, improved access to clinical specimens for validation of diagnostics would help to accelerate development of new tests. These gaps should be addressed by updated target product profiles for CCHFV diagnostics.",2019 Feb 20,"['Mazzola, Laura T', 'Kelly-Cirino, Cassandra']",BMJ Glob Health,,,True
bd569ba913bfaf39a1a9b3004ef26ae9503f7def,PMC,Diagnostic tests for Crimean-Congo haemorrhagic fever: a widespread tickborne disease,http://dx.doi.org/10.1136/bmjgh-2018-001114,PMC6407549,30899574,CC BY,"Crimean-Congo haemorrhagic fever (CCHF) is a widespread tickborne disease that circulates in wild and domestic animal hosts, and causes severe and often fatal haemorrhagic fever in infected humans. Due to the lack of treatment options or vaccines, and a high fatality rate, CCHF virus (CCHFV) is considered a high-priority pathogen according to the WHO R&D Blueprint. Several commercial reverse transcriptase PCR (RT-PCR) and serological diagnostic assays for CCHFV are already available, including febrile agent panels to distinguish CCHFV from other viral haemorrhagic fever agents; however, the majority of international laboratories use inhouse assays. As CCHFV has numerous amplifying animal hosts, a cross-sectoral ‘One Health’ approach to outbreak prevention is recommended to enhance notifications and enable early warning for genetic and epidemiological shifts in the human, animal and tick populations. However, a lack of guidance for surveillance in animals, harmonisation of case identification and validated serodiagnostic kits for animal testing hinders efforts to strengthen surveillance systems. Additionally, as RT-PCR tests tend to be lineage-specific for regional circulating strains, there is a need for pan-lineage sensitive diagnostics. Adaptation of existing tests to point-of-care molecular diagnostic platforms that can be implemented in clinic or field-based settings would be of value given the potential for CCHFV outbreaks in remote or low-resource areas. Finally, improved access to clinical specimens for validation of diagnostics would help to accelerate development of new tests. These gaps should be addressed by updated target product profiles for CCHFV diagnostics.",2019 Feb 20,"['Mazzola, Laura T', 'Kelly-Cirino, Cassandra']",BMJ Glob Health,,,False
b5ded754c8f35d1b6d6263866640042cf62c53b9,PMC,Diagnostic tests for Crimean-Congo haemorrhagic fever: a widespread tickborne disease,http://dx.doi.org/10.1136/bmjgh-2018-001114,PMC6407549,30899574,CC BY,"Crimean-Congo haemorrhagic fever (CCHF) is a widespread tickborne disease that circulates in wild and domestic animal hosts, and causes severe and often fatal haemorrhagic fever in infected humans. Due to the lack of treatment options or vaccines, and a high fatality rate, CCHF virus (CCHFV) is considered a high-priority pathogen according to the WHO R&D Blueprint. Several commercial reverse transcriptase PCR (RT-PCR) and serological diagnostic assays for CCHFV are already available, including febrile agent panels to distinguish CCHFV from other viral haemorrhagic fever agents; however, the majority of international laboratories use inhouse assays. As CCHFV has numerous amplifying animal hosts, a cross-sectoral ‘One Health’ approach to outbreak prevention is recommended to enhance notifications and enable early warning for genetic and epidemiological shifts in the human, animal and tick populations. However, a lack of guidance for surveillance in animals, harmonisation of case identification and validated serodiagnostic kits for animal testing hinders efforts to strengthen surveillance systems. Additionally, as RT-PCR tests tend to be lineage-specific for regional circulating strains, there is a need for pan-lineage sensitive diagnostics. Adaptation of existing tests to point-of-care molecular diagnostic platforms that can be implemented in clinic or field-based settings would be of value given the potential for CCHFV outbreaks in remote or low-resource areas. Finally, improved access to clinical specimens for validation of diagnostics would help to accelerate development of new tests. These gaps should be addressed by updated target product profiles for CCHFV diagnostics.",2019 Feb 20,"['Mazzola, Laura T', 'Kelly-Cirino, Cassandra']",BMJ Glob Health,,,False
b62a6f960eba7bb8d0a1bbc31a9bcbf1dd59317b,PMC,Diagnostic tests for Crimean-Congo haemorrhagic fever: a widespread tickborne disease,http://dx.doi.org/10.1136/bmjgh-2018-001114,PMC6407549,30899574,CC BY,"Crimean-Congo haemorrhagic fever (CCHF) is a widespread tickborne disease that circulates in wild and domestic animal hosts, and causes severe and often fatal haemorrhagic fever in infected humans. Due to the lack of treatment options or vaccines, and a high fatality rate, CCHF virus (CCHFV) is considered a high-priority pathogen according to the WHO R&D Blueprint. Several commercial reverse transcriptase PCR (RT-PCR) and serological diagnostic assays for CCHFV are already available, including febrile agent panels to distinguish CCHFV from other viral haemorrhagic fever agents; however, the majority of international laboratories use inhouse assays. As CCHFV has numerous amplifying animal hosts, a cross-sectoral ‘One Health’ approach to outbreak prevention is recommended to enhance notifications and enable early warning for genetic and epidemiological shifts in the human, animal and tick populations. However, a lack of guidance for surveillance in animals, harmonisation of case identification and validated serodiagnostic kits for animal testing hinders efforts to strengthen surveillance systems. Additionally, as RT-PCR tests tend to be lineage-specific for regional circulating strains, there is a need for pan-lineage sensitive diagnostics. Adaptation of existing tests to point-of-care molecular diagnostic platforms that can be implemented in clinic or field-based settings would be of value given the potential for CCHFV outbreaks in remote or low-resource areas. Finally, improved access to clinical specimens for validation of diagnostics would help to accelerate development of new tests. These gaps should be addressed by updated target product profiles for CCHFV diagnostics.",2019 Feb 20,"['Mazzola, Laura T', 'Kelly-Cirino, Cassandra']",BMJ Glob Health,,,False
c04cea5393ee21d23a0d8257fc67fecb57899a38,PMC,Diagnostics for Lassa fever virus: a genetically diverse pathogen found in low-resource settings,http://dx.doi.org/10.1136/bmjgh-2018-001116,PMC6407561,30899575,CC BY,"Lassa fever virus (LASV) causes acute viral haemorrhagic fever with symptoms similar to those seen with Ebola virus infections. LASV is endemic to West Africa and is transmitted through contact with excretions of infected Mastomys natalensis rodents and other rodent species. Due to a high fatality rate, lack of treatment options and difficulties with prevention and control, LASV is one of the high-priority pathogens included in the WHO R&D Blueprint. The WHO LASV vaccine strategy relies on availability of effective diagnostic tests. Current diagnostics for LASV include in-house and commercial (primarily research-only) laboratory-based serological and nucleic acid amplification tests. There are two commercially available (for research use only) rapid diagnostic tests (RDTs), and a number of multiplex panels for differential detection of LASV infection from other endemic diseases with similar symptoms have been evaluated. However, a number of diagnostic gaps remain. Lineage detection is a challenge due to the genomic diversity of LASV, as pan-lineage sensitivity for both molecular and immunological detection is necessary for surveillance and outbreak response. While pan-lineage ELISA and RDTs are commercially available (for research use only), validation and external quality assessment (EQA) is needed to confirm detection sensitivity for all known or relevant strains. Variable sensitivity of LASV PCR tests also highlights the need for improved validation and EQA. Given that LASV outbreaks typically occur in low-resource settings, more options for point-of-care testing would be valuable. These requirements should be taken into account in target product profiles for improved LASV diagnostics.",2019 Feb 7,"['Mazzola, Laura T', 'Kelly-Cirino, Cassandra']",BMJ Glob Health,,,True
fd3ef6bda4997bbad255cdfa77eb5f58c562a06e,PMC,Diagnostics for Lassa fever virus: a genetically diverse pathogen found in low-resource settings,http://dx.doi.org/10.1136/bmjgh-2018-001116,PMC6407561,30899575,CC BY,"Lassa fever virus (LASV) causes acute viral haemorrhagic fever with symptoms similar to those seen with Ebola virus infections. LASV is endemic to West Africa and is transmitted through contact with excretions of infected Mastomys natalensis rodents and other rodent species. Due to a high fatality rate, lack of treatment options and difficulties with prevention and control, LASV is one of the high-priority pathogens included in the WHO R&D Blueprint. The WHO LASV vaccine strategy relies on availability of effective diagnostic tests. Current diagnostics for LASV include in-house and commercial (primarily research-only) laboratory-based serological and nucleic acid amplification tests. There are two commercially available (for research use only) rapid diagnostic tests (RDTs), and a number of multiplex panels for differential detection of LASV infection from other endemic diseases with similar symptoms have been evaluated. However, a number of diagnostic gaps remain. Lineage detection is a challenge due to the genomic diversity of LASV, as pan-lineage sensitivity for both molecular and immunological detection is necessary for surveillance and outbreak response. While pan-lineage ELISA and RDTs are commercially available (for research use only), validation and external quality assessment (EQA) is needed to confirm detection sensitivity for all known or relevant strains. Variable sensitivity of LASV PCR tests also highlights the need for improved validation and EQA. Given that LASV outbreaks typically occur in low-resource settings, more options for point-of-care testing would be valuable. These requirements should be taken into account in target product profiles for improved LASV diagnostics.",2019 Feb 7,"['Mazzola, Laura T', 'Kelly-Cirino, Cassandra']",BMJ Glob Health,,,False
49a2ef37aee66bee1931652909a4b29db4f7f964,PMC,Diagnostics for Lassa fever virus: a genetically diverse pathogen found in low-resource settings,http://dx.doi.org/10.1136/bmjgh-2018-001116,PMC6407561,30899575,CC BY,"Lassa fever virus (LASV) causes acute viral haemorrhagic fever with symptoms similar to those seen with Ebola virus infections. LASV is endemic to West Africa and is transmitted through contact with excretions of infected Mastomys natalensis rodents and other rodent species. Due to a high fatality rate, lack of treatment options and difficulties with prevention and control, LASV is one of the high-priority pathogens included in the WHO R&D Blueprint. The WHO LASV vaccine strategy relies on availability of effective diagnostic tests. Current diagnostics for LASV include in-house and commercial (primarily research-only) laboratory-based serological and nucleic acid amplification tests. There are two commercially available (for research use only) rapid diagnostic tests (RDTs), and a number of multiplex panels for differential detection of LASV infection from other endemic diseases with similar symptoms have been evaluated. However, a number of diagnostic gaps remain. Lineage detection is a challenge due to the genomic diversity of LASV, as pan-lineage sensitivity for both molecular and immunological detection is necessary for surveillance and outbreak response. While pan-lineage ELISA and RDTs are commercially available (for research use only), validation and external quality assessment (EQA) is needed to confirm detection sensitivity for all known or relevant strains. Variable sensitivity of LASV PCR tests also highlights the need for improved validation and EQA. Given that LASV outbreaks typically occur in low-resource settings, more options for point-of-care testing would be valuable. These requirements should be taken into account in target product profiles for improved LASV diagnostics.",2019 Feb 7,"['Mazzola, Laura T', 'Kelly-Cirino, Cassandra']",BMJ Glob Health,,,False
1d5d15ec38c6bf042a105c28dca5222eb976975b,PMC,Diagnostics for Lassa fever virus: a genetically diverse pathogen found in low-resource settings,http://dx.doi.org/10.1136/bmjgh-2018-001116,PMC6407561,30899575,CC BY,"Lassa fever virus (LASV) causes acute viral haemorrhagic fever with symptoms similar to those seen with Ebola virus infections. LASV is endemic to West Africa and is transmitted through contact with excretions of infected Mastomys natalensis rodents and other rodent species. Due to a high fatality rate, lack of treatment options and difficulties with prevention and control, LASV is one of the high-priority pathogens included in the WHO R&D Blueprint. The WHO LASV vaccine strategy relies on availability of effective diagnostic tests. Current diagnostics for LASV include in-house and commercial (primarily research-only) laboratory-based serological and nucleic acid amplification tests. There are two commercially available (for research use only) rapid diagnostic tests (RDTs), and a number of multiplex panels for differential detection of LASV infection from other endemic diseases with similar symptoms have been evaluated. However, a number of diagnostic gaps remain. Lineage detection is a challenge due to the genomic diversity of LASV, as pan-lineage sensitivity for both molecular and immunological detection is necessary for surveillance and outbreak response. While pan-lineage ELISA and RDTs are commercially available (for research use only), validation and external quality assessment (EQA) is needed to confirm detection sensitivity for all known or relevant strains. Variable sensitivity of LASV PCR tests also highlights the need for improved validation and EQA. Given that LASV outbreaks typically occur in low-resource settings, more options for point-of-care testing would be valuable. These requirements should be taken into account in target product profiles for improved LASV diagnostics.",2019 Feb 7,"['Mazzola, Laura T', 'Kelly-Cirino, Cassandra']",BMJ Glob Health,,,False
264b30686ef5ca001923b9820e7d96fdb74e268e,PMC,Phylogeny matters: revisiting ‘a comparison of bats and rodents as reservoirs of zoonotic viruses’,http://dx.doi.org/10.1098/rsos.181182,PMC6408376,30891262,CC BY,"Diseases emerging from wildlife have been the source of many major human outbreaks. Predicting key sources of these outbreaks requires an understanding of the factors that explain pathogen diversity in reservoir species. Comparative methods are powerful tools for understanding variation in pathogen diversity and rely on correcting for phylogenetic relatedness among reservoir species. We reanalysed a previously published dataset, examining the relative effects of species' traits on patterns of viral diversity in bats and rodents. We expanded on prior work by using more highly resolved phylogenies for bats and rodents and incorporating a phylogenetically controlled principal components analysis. For rodents, sympatry and torpor use were important predictors of viral richness and, as previously reported, phylogeny had minimal impact in models. For bats, in contrast to prior work, we find that phylogeny does have an effect in models. Patterns of viral diversity in bats were related to geographical distribution (i.e. latitude and range size) and life history (i.e. lifespan, body size and birthing frequency). However, the effects of these predictors were marginal relative to citation count, emphasizing that the ability to accurately assess reservoir status largely depends on sampling effort and highlighting the need for additional data in future comparative studies.",2019 Feb 13,"['Guy, Cylita', 'Thiagavel, Jeneni', 'Mideo, Nicole', 'Ratcliffe, John M.']",R Soc Open Sci,,,True
bd246a6d199cb961f7c4c3421d22324aface4ff4,PMC,Phylogeny matters: revisiting ‘a comparison of bats and rodents as reservoirs of zoonotic viruses’,http://dx.doi.org/10.1098/rsos.181182,PMC6408376,30891262,CC BY,"Diseases emerging from wildlife have been the source of many major human outbreaks. Predicting key sources of these outbreaks requires an understanding of the factors that explain pathogen diversity in reservoir species. Comparative methods are powerful tools for understanding variation in pathogen diversity and rely on correcting for phylogenetic relatedness among reservoir species. We reanalysed a previously published dataset, examining the relative effects of species' traits on patterns of viral diversity in bats and rodents. We expanded on prior work by using more highly resolved phylogenies for bats and rodents and incorporating a phylogenetically controlled principal components analysis. For rodents, sympatry and torpor use were important predictors of viral richness and, as previously reported, phylogeny had minimal impact in models. For bats, in contrast to prior work, we find that phylogeny does have an effect in models. Patterns of viral diversity in bats were related to geographical distribution (i.e. latitude and range size) and life history (i.e. lifespan, body size and birthing frequency). However, the effects of these predictors were marginal relative to citation count, emphasizing that the ability to accurately assess reservoir status largely depends on sampling effort and highlighting the need for additional data in future comparative studies.",2019 Feb 13,"['Guy, Cylita', 'Thiagavel, Jeneni', 'Mideo, Nicole', 'Ratcliffe, John M.']",R Soc Open Sci,,,True
1bb908e3833b1882de4b7a04593005dbe9e5cd1e,PMC,Contact chains of cattle farms in Great Britain,http://dx.doi.org/10.1098/rsos.180719,PMC6408381,30891255,CC BY,"Network analyses can assist in predicting the course of epidemics. Time-directed paths or ‘contact chains' provide a measure of host-connectedness across specified timeframes, and so represent potential pathways for spread of infections with different epidemiological characteristics. We analysed networks and contact chains of cattle farms in Great Britain using Cattle Tracing System data from 2001 to 2015. We focused on the potential for between-farm transmission of bovine tuberculosis, a chronic infection with potential for hidden spread through the network. Networks were characterized by scale-free type properties, where individual farms were found to be influential ‘hubs' in the network. We found a markedly bimodal distribution of farms with either small or very large ingoing and outgoing contact chains (ICCs and OCCs). As a result of their cattle purchases within 12-month periods, 47% of British farms were connected by ICCs to more than 1000 other farms and 16% were connected to more than 10 000 other farms. As a result of their cattle sales within 12-month periods, 66% of farms had OCCs that reached more than 1000 other farms and 15% reached more than 10 000 other farms. Over 19 000 farms had both ICCs and OCCs reaching more than 10 000 farms for two or more years. While farms with more contacts in their ICCs or OCCs might play an important role in disease spread, farms with extensive ICCs and OCCs might be particularly important by being at higher risk of both acquiring and disseminating infections.",2019 Feb 27,"['Fielding, Helen R.', 'McKinley, Trevelyan J.', 'Silk, Matthew J.', 'Delahay, Richard J.', 'McDonald, Robbie A.']",R Soc Open Sci,,,True
e1d7e7883ad7d77a1c982c700f77e5ce09530fcf,PMC,Contact chains of cattle farms in Great Britain,http://dx.doi.org/10.1098/rsos.180719,PMC6408381,30891255,CC BY,"Network analyses can assist in predicting the course of epidemics. Time-directed paths or ‘contact chains' provide a measure of host-connectedness across specified timeframes, and so represent potential pathways for spread of infections with different epidemiological characteristics. We analysed networks and contact chains of cattle farms in Great Britain using Cattle Tracing System data from 2001 to 2015. We focused on the potential for between-farm transmission of bovine tuberculosis, a chronic infection with potential for hidden spread through the network. Networks were characterized by scale-free type properties, where individual farms were found to be influential ‘hubs' in the network. We found a markedly bimodal distribution of farms with either small or very large ingoing and outgoing contact chains (ICCs and OCCs). As a result of their cattle purchases within 12-month periods, 47% of British farms were connected by ICCs to more than 1000 other farms and 16% were connected to more than 10 000 other farms. As a result of their cattle sales within 12-month periods, 66% of farms had OCCs that reached more than 1000 other farms and 15% reached more than 10 000 other farms. Over 19 000 farms had both ICCs and OCCs reaching more than 10 000 farms for two or more years. While farms with more contacts in their ICCs or OCCs might play an important role in disease spread, farms with extensive ICCs and OCCs might be particularly important by being at higher risk of both acquiring and disseminating infections.",2019 Feb 27,"['Fielding, Helen R.', 'McKinley, Trevelyan J.', 'Silk, Matthew J.', 'Delahay, Richard J.', 'McDonald, Robbie A.']",R Soc Open Sci,,,True
8dd8d40c08edb208f9a32333f21a24d4dbfdb6c4,PMC,Decline of transmissible gastroenteritis virus and its complex evolutionary relationship with porcine respiratory coronavirus in the United States,http://dx.doi.org/10.1038/s41598-019-40564-z,PMC6408454,30850666,CC BY,"The epidemiology and genetic diversity of transmissible gastroenteritis virus (TGEV) in the United States (US) was investigated by testing clinical cases for TGEV by real time RT-PCR between January 2008 and November 2016. Prevalence of TGEV ranged between 3.8–6.8% and peaked during cold months until March 2013, in which prevalence decreased to < 0.1%. Nineteen complete TGEV genomes and a single strain of porcine respiratory coronavirus (PRCV) from the US were generated and compared to historical strains to investigate the evolution of these endemic coronaviruses. Sixteen of our TGEV strains share 8 unique deletions and 119 distinct amino acid changes, which might greatly affect the biological characteristics of the variant TGEV, and resulted in a “variant” genotype of TGEV. The “variant” genotype shared similar unique deletions and amino acid changes with the recent PRCV strain identified in this study, suggesting a recombination event occurred between the ‘‘variant’’ TGEV and PRCV. Moreover, the results indicate the “variant” genotype is the dominant genotype circulating in the US. Therefore, this study provides insight into the occurrence, origin, genetic characteristics, and evolution of TGEV and PRCV circulating in the US.",2019 Mar 8,"['Chen, Fangzhou', 'Knutson, Todd P.', 'Rossow, Stephanie', 'Saif, Linda J.', 'Marthaler, Douglas G.']",Sci Rep,,,True
260203fe9a476037ca41765c677af4b844573d36,PMC,"Chemical Constituents and an Antineuroinflammatory Lignan, Savinin from the Roots of Acanthopanax henryi",http://dx.doi.org/10.1155/2019/1856294,PMC6409005,30915141,CC BY,"The phytochemical investigation on the roots of Acanthopanax henryi (Araliaceae) resulted in the discovery of twenty compounds whose chemical structures were elucidated by the analysis of 1D-, 2D-NMR, mass spectrometry data, other physicochemical properties, and a comparison of the spectral data with the literature. They were identified as (-)-sesamin (1), helioxanthin (2), savinin (3), taiwanin C (4), 6-methoxy-7-hydroxycoumarin (5), behenic acid (6), 3-O-caffeoyl-quinic acid (7), 5-O-caffeoyl-quinic acid (8), 1,3-di-O-caffeoyl-quinic acid (9), 1,4-di-O-caffeoyl-quinic acid (10), 1,5-di-O-caffeoyl-quinic acid (11), (+)-threo-(7R,8R)-guaiacylglycerol-β-coniferyl aldehyde ether (12), (+)-erythro-(7S,8R)-guaiacylglycerol-β-coniferyl aldehyde ether (13), ferulic acid (14), caffeic acid (15), stigmasterol (16), β-sitosterol (17), adenosine (18), syringin (19), and trans-coniferin (20). Among these isolates, compound 3 showed inhibitory activity against lipopolysaccharide- (LPS-) induced nitric oxide (NO) and prostaglandin E2 (PGE(2)) production with IC(50) values of 2.22 ± 0.11 and 2.28 ± 0.23 μM, respectively. The effects of compound 3 were associated with the suppression of LPS-induced expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein. Furthermore, compound 3 negatively regulated the production of interleukin- (IL-) 1β and tumor-necrosis factor- (TNF-) α at the transcriptional level in LPS-stimulated BV2 microglial cells. These antineuroinflammatory effects of compound 3 were mediated by p38 mitogen-activated protein kinase (MAPK).",2019 Feb 21,"['Li, Xiao-Jun', 'Kim, Kwan-Woo', 'Oh, Hyuncheol', 'Liu, Xiang-Qian', 'Kim, Youn-Chul']",Evid Based Complement Alternat Med,,,True
34db03a4932a3007f410e5e1735451f22f72765c,PMC,Local Antigen Encounter Is Essential for Establishing Persistent CD8(+) T-Cell Memory in the CNS,http://dx.doi.org/10.3389/fimmu.2019.00351,PMC6409353,30886617,CC BY,"While the brain is considered an immune-privileged site, the CNS may nevertheless be the focus of immune mediated inflammation in the case of infection and certain autoimmune diseases, e.g., multiple sclerosis. As in other tissues, it has been found that acute T-cell infiltration may be followed by establishment of persistent local T-cell memory. To improve our understanding regarding the regulation of putative tissue resident memory T (Trm) cells in CNS, we devised a new model system for studying the generation of Trm cells in this site. To this purpose, we exploited the fact that the CNS may be a sanctuary for adenoviral infection, and to minimize virus-induced disease, we chose replication-deficient adenoviruses for infection of the CNS. Non-replicating adenoviruses are known to be highly immunogenic, and our studies demonstrate that intracerebral inoculation causes marked local T-cell recruitment, which is followed by persistent infiltration of the CNS parenchyma by antigen specific CD8(+) T cells. Phenotypical analysis of CNS infiltrating antigen specific CD8(+) T cells was consistent with these cells being Trms. Regarding the long-term stability of the infiltrate, resident CD8(+) T cells expressed high levels of the anti-apoptotic molecule Bcl-2 as well as the proliferation marker Ki-67 suggesting that the population is maintained through steady homeostatic proliferation. Functionally, memory CD8(+) T cells from CNS matched peripheral memory cells with regard to capacity for ex vivo cytotoxicity and cytokine production. Most importantly, our experiments revealed a key role for local antigen encounter in the establishment of sustained CD8(+) T-cell memory in the brain. Inflammation in the absence of cognate antigen only led to limited and transient infiltration by antigen specific CD8(+) T cells. Together these results indicate that memory CD8(+) T cells residing in the CNS predominantly mirror previous local infections and immune responses to local autoantigens.",2019 Mar 4,"['Schøller, Amalie S.', 'Fonnes, Masja', 'Nazerai, Loulieta', 'Christensen, Jan P.', 'Thomsen, Allan R.']",Front Immunol,,,False
f7ff81d2d3ae773aa28836cc485617983d7499ef,PMC,Local Antigen Encounter Is Essential for Establishing Persistent CD8(+) T-Cell Memory in the CNS,http://dx.doi.org/10.3389/fimmu.2019.00351,PMC6409353,30886617,CC BY,"While the brain is considered an immune-privileged site, the CNS may nevertheless be the focus of immune mediated inflammation in the case of infection and certain autoimmune diseases, e.g., multiple sclerosis. As in other tissues, it has been found that acute T-cell infiltration may be followed by establishment of persistent local T-cell memory. To improve our understanding regarding the regulation of putative tissue resident memory T (Trm) cells in CNS, we devised a new model system for studying the generation of Trm cells in this site. To this purpose, we exploited the fact that the CNS may be a sanctuary for adenoviral infection, and to minimize virus-induced disease, we chose replication-deficient adenoviruses for infection of the CNS. Non-replicating adenoviruses are known to be highly immunogenic, and our studies demonstrate that intracerebral inoculation causes marked local T-cell recruitment, which is followed by persistent infiltration of the CNS parenchyma by antigen specific CD8(+) T cells. Phenotypical analysis of CNS infiltrating antigen specific CD8(+) T cells was consistent with these cells being Trms. Regarding the long-term stability of the infiltrate, resident CD8(+) T cells expressed high levels of the anti-apoptotic molecule Bcl-2 as well as the proliferation marker Ki-67 suggesting that the population is maintained through steady homeostatic proliferation. Functionally, memory CD8(+) T cells from CNS matched peripheral memory cells with regard to capacity for ex vivo cytotoxicity and cytokine production. Most importantly, our experiments revealed a key role for local antigen encounter in the establishment of sustained CD8(+) T-cell memory in the brain. Inflammation in the absence of cognate antigen only led to limited and transient infiltration by antigen specific CD8(+) T cells. Together these results indicate that memory CD8(+) T cells residing in the CNS predominantly mirror previous local infections and immune responses to local autoantigens.",2019 Mar 4,"['Schøller, Amalie S.', 'Fonnes, Masja', 'Nazerai, Loulieta', 'Christensen, Jan P.', 'Thomsen, Allan R.']",Front Immunol,,,True
e192e65a6546583fe49086c4d3ac29a0620d5bd5,PMC,Effect of Pullet Vaccination on Development and Longevity of Immunity,http://dx.doi.org/10.3390/v11020135,PMC6409539,30717342,CC BY,"Avian respiratory disease causes significant economic losses in commercial poultry. Because of the need to protect long-lived poultry against respiratory tract pathogens from an early age, vaccination programs for pullets typically involve serial administration of a variety of vaccines, including infectious bronchitis virus (IBV), Newcastle disease virus (NDV), and infectious laryngotracheitis virus (ILTV). Often the interval between vaccinations is only a matter of weeks, yet it is unknown whether the development of immunity and protection against challenge when vaccines are given in short succession occurs in these birds, something known as viral interference. Our objective was to determine whether serially administered, live attenuated vaccines against IBV, NDV, and ILTV influence the development and longevity of immunity and protection against challenge in long-lived birds. Based on a typical pullet vaccination program, specific-pathogen-free white leghorns were administered multiple live attenuated vaccines against IBV, NDV, and ILTV until 16 weeks of age (WOA), after which certain groups were challenged with IBV, NDV, or ILTV at 20, 24, 28, 32, and 36 WOA. Five days post-challenge, viral load, clinical signs, ciliostasis, tracheal histopathology, and antibody titers in serum and tears were evaluated. We demonstrate that pullets serially administered live attenuated vaccines against IBV, NDV, and ILTV were protected against homologous challenge with IBV, NDV, or ILTV for at least 36 weeks, and conclude that the interval between vaccinations used in this study (at least 2 weeks) did not interfere with protection. This information is important because it shows that a typical pullet vaccination program consisting of serially administered live attenuated vaccines against multiple respiratory pathogens can result in the development of protective immunity against each disease agent.",2019 Feb 2,"['Aston, Emily J.', 'Jordan, Brian J.', 'Williams, Susan M.', 'García, Maricarmen', 'Jackwood, Mark W.']",Viruses,,,True
7c0e41727a796451e68029e772c970246b71824c,PMC,Global Epidemiology of Bat Coronaviruses,http://dx.doi.org/10.3390/v11020174,PMC6409556,30791586,CC BY,"Bats are a unique group of mammals of the order Chiroptera. They are highly diversified and are the group of mammals with the second largest number of species. Such highly diversified cell types and receptors facilitate them to be potential hosts of a large variety of viruses. Bats are the only group of mammals capable of sustained flight, which enables them to disseminate the viruses they harbor and enhance the chance of interspecies transmission. This article aims at reviewing the various aspects of the global epidemiology of bat coronaviruses (CoVs). Before the SARS epidemic, bats were not known to be hosts for CoVs. In the last 15 years, bats have been found to be hosts of >30 CoVs with complete genomes sequenced, and many more if those without genome sequences are included. Among the four CoV genera, only alphaCoVs and betaCoVs have been found in bats. As a whole, both alphaCoVs and betaCoVs have been detected from bats in Asia, Europe, Africa, North and South America and Australasia; but alphaCoVs seem to be more widespread than betaCoVs, and their detection rate is also higher. For betaCoVs, only those from subgenera Sarbecovirus, Merbecovirus, Nobecovirus and Hibecovirus have been detected in bats. Most notably, horseshoe bats are the reservoir of SARS-CoV, and several betaCoVs from subgenus Merbecovirus are closely related to MERS-CoV. In addition to the interactions among various bat species themselves, bat–animal and bat–human interactions, such as the presence of live bats in wildlife wet markets and restaurants in Southern China, are important for interspecies transmission of CoVs and may lead to devastating global outbreaks.",2019 Feb 20,"['Wong, Antonio C. P.', 'Li, Xin', 'Lau, Susanna K. P.', 'Woo, Patrick C. Y.']",Viruses,,,True
d1757146383c42ebfb3f6318f2fd63dc1b43f1fe,PMC,Dynamic Expression of Interferon Lambda Regulated Genes in Primary Fibroblasts and Immune Organs of the Chicken,http://dx.doi.org/10.3390/genes10020145,PMC6409627,30769908,CC BY,"Interferons (IFNs) are pleiotropic cytokines that establish a first line of defense against viral infections in vertebrates. Several types of IFN have been identified; however, limited information is available in poultry, especially using live animal experimental models. IFN-lambda (IFN-λ) has recently been shown to exert a significant antiviral impact against viral pathogens in mammals. In order to investigate the in vivo potential of chicken IFN-λ (chIFN-λ) as a regulator of innate immunity, and potential antiviral therapeutics, we profiled the transcriptome of chIFN-λ-stimulated chicken immune organs (in vivo) and compared it with primary chicken embryo fibroblasts (in vitro). Employing the baculovirus expression vector system (BEVS), recombinant chIFN-λ3 (rchIFN-λ3) was produced and its biological activities were demonstrated. The rchIFNλ3 induced a great array of IFN-regulated genes in primary chicken fibroblast cells. The transcriptional profiling using RNA-seq and subsequent bioinformatics analysis (gene ontology, differential expressed genes, and KEGGs analysis) of the bursa of Fabricious and the thymus demonstrated an upregulation of crucial immune genes (viperin, IKKB, CCL5, IL1β, and AP1) as well as the antiviral signaling pathways. Interestingly, this experimental approach revealed contrasting evidence of the antiviral potential of chIFN-λ in both in vivo and in vitro models. Taken together, our data signifies the potential of chIFN-λ as a potent antiviral cytokine and highlights its future possible use as an antiviral therapeutic in poultry.",2019 Feb 14,"['Arslan, Mehboob', 'Yang, Xin', 'Santhakumar, Diwakar', 'Liu, Xingjian', 'Hu, Xiaoyuan', 'Munir, Muhammad', 'Li, Yinü', 'Zhang, Zhifang']",Genes (Basel),,,True
9000d72e1e522099e6a53feeda6aa6d884a1b179,PMC,Shared Common Ancestry of Rodent Alphacoronaviruses Sampled Globally,http://dx.doi.org/10.3390/v11020125,PMC6409636,30704076,CC BY,"The recent discovery of novel alphacoronaviruses (alpha-CoVs) in European and Asian rodents revealed that rodent coronaviruses (CoVs) sampled worldwide formed a discrete phylogenetic group within this genus. To determine the evolutionary history of rodent CoVs in more detail, particularly the relative frequencies of virus-host co-divergence and cross-species transmission, we recovered longer fragments of CoV genomes from previously discovered European rodent alpha-CoVs using a combination of PCR and high-throughput sequencing. Accordingly, the full genome sequence was retrieved from the UK rat coronavirus, along with partial genome sequences from the UK field vole and Poland-resident bank vole CoVs, and a short conserved ORF1b fragment from the French rabbit CoV. Genome and phylogenetic analysis showed that despite their diverse geographic origins, all rodent alpha-CoVs formed a single monophyletic group and shared similar features, such as the same gene constellations, a recombinant beta-CoV spike gene, and similar core transcriptional regulatory sequences (TRS). These data suggest that all rodent alpha CoVs sampled so far originate from a single common ancestor, and that there has likely been a long-term association between alpha CoVs and rodents. Despite this likely antiquity, the phylogenetic pattern of the alpha-CoVs was also suggestive of relatively frequent host-jumping among the different rodent species.",2019 Jan 30,"['Tsoleridis, Theocharis', 'Chappell, Joseph G.', 'Onianwa, Okechukwu', 'Marston, Denise A.', 'Fooks, Anthony R.', 'Monchatre-Leroy, Elodie', 'Umhang, Gérald', 'Müller, Marcel A.', 'Drexler, Jan F.', 'Drosten, Christian', 'Tarlinton, Rachael E.', 'McClure, Charles P.', 'Holmes, Edward C.', 'Ball, Jonathan K.']",Viruses,,,True
e75d46e465c19d11c3af73243256ab4940062d14,PMC,Shared Common Ancestry of Rodent Alphacoronaviruses Sampled Globally,http://dx.doi.org/10.3390/v11020125,PMC6409636,30704076,CC BY,"The recent discovery of novel alphacoronaviruses (alpha-CoVs) in European and Asian rodents revealed that rodent coronaviruses (CoVs) sampled worldwide formed a discrete phylogenetic group within this genus. To determine the evolutionary history of rodent CoVs in more detail, particularly the relative frequencies of virus-host co-divergence and cross-species transmission, we recovered longer fragments of CoV genomes from previously discovered European rodent alpha-CoVs using a combination of PCR and high-throughput sequencing. Accordingly, the full genome sequence was retrieved from the UK rat coronavirus, along with partial genome sequences from the UK field vole and Poland-resident bank vole CoVs, and a short conserved ORF1b fragment from the French rabbit CoV. Genome and phylogenetic analysis showed that despite their diverse geographic origins, all rodent alpha-CoVs formed a single monophyletic group and shared similar features, such as the same gene constellations, a recombinant beta-CoV spike gene, and similar core transcriptional regulatory sequences (TRS). These data suggest that all rodent alpha CoVs sampled so far originate from a single common ancestor, and that there has likely been a long-term association between alpha CoVs and rodents. Despite this likely antiquity, the phylogenetic pattern of the alpha-CoVs was also suggestive of relatively frequent host-jumping among the different rodent species.",2019 Jan 30,"['Tsoleridis, Theocharis', 'Chappell, Joseph G.', 'Onianwa, Okechukwu', 'Marston, Denise A.', 'Fooks, Anthony R.', 'Monchatre-Leroy, Elodie', 'Umhang, Gérald', 'Müller, Marcel A.', 'Drexler, Jan F.', 'Drosten, Christian', 'Tarlinton, Rachael E.', 'McClure, Charles P.', 'Holmes, Edward C.', 'Ball, Jonathan K.']",Viruses,,,False
a1086d8acf9fe3ae22d83443b0935ecb80f3142a,PMC,Investigation of the Quantity of Exhaled Aerosols Released into the Environment during Nebulisation,http://dx.doi.org/10.3390/pharmaceutics11020075,PMC6409895,30759879,CC BY,"Background: Secondary inhalation of medical aerosols is a significant occupational hazard in both clinical and homecare settings. Exposure to fugitive emissions generated during aerosol therapy increases the risk of the unnecessary inhalation of medication, as well as toxic side effects. Methods: This study examines fugitively-emitted aerosol emissions when nebulising albuterol sulphate, as a tracer aerosol, using two commercially available nebulisers in combination with an open or valved facemask or using a mouthpiece with and without a filter on the exhalation port. Each combination was connected to a breathing simulator during simulated adult breathing. The inhaled dose and residual mass were quantified using UV spectrophotometry. Time-varying fugitively-emitted aerosol concentrations and size distributions during nebulisation were recorded using aerodynamic particle sizers at two distances relative to the simulated patient. Different aerosol concentrations and size distributions were observed depending on the interface. Results: Within each nebuliser, the facemask combination had the highest time-averaged fugitively-emitted aerosol concentration, and values up to 0.072 ± 0.001 mg m(−3) were recorded. The placement of a filter on the exhalation port of the mouthpiece yielded the lowest recorded concentrations. The mass median aerodynamic diameter of the fugitively-emitted aerosol was recorded as 0.890 ± 0.044 µm, lower the initially generated medical aerosol in the range of 2–5 µm. Conclusions: The results highlight the potential secondary inhalation of exhaled aerosols from commercially available nebuliser facemask/mouthpiece combinations. The results will aid in developing approaches to inform policy and best practices for risk mitigation from fugitive emissions.",2019 Feb 12,"['McGrath, James A.', 'O’Sullivan, Andrew', 'Bennett, Gavin', 'O’Toole, Ciarraí', 'Joyce, Mary', 'Byrne, Miriam A.', 'MacLoughlin, Ronan']",Pharmaceutics,,,True
edee1fd45587a0a71d88a5db58cc81342840e2f6,PMC,Characterization of Host and Bacterial Contributions to Lung Barrier Dysfunction Following Co-infection with 2009 Pandemic Influenza and Methicillin Resistant Staphylococcus aureus,http://dx.doi.org/10.3390/v11020116,PMC6409999,30699912,CC BY,"Influenza viruses are a threat to global public health resulting in ~500,000 deaths each year. Despite an intensive vaccination program, influenza infections remain a recurrent, yet unsolved public health problem. Secondary bacterial infections frequently complicate influenza infections during seasonal outbreaks and pandemics, resulting in increased morbidity and mortality. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is frequently associated with these co-infections, including the 2009 influenza pandemic. Damage to alveolar epithelium is a major contributor to severe influenza-bacterial co-infections and can result in gas exchange abnormalities, fluid leakage, and respiratory insufficiency. These deleterious manifestations likely involve both pathogen- and host-mediated mechanisms. However, there is a paucity of information regarding the mechanisms (pathogen- and/or host-mediated) underlying influenza-bacterial co-infection pathogenesis. To address this, we characterized the contributions of viral-, bacterial-, and host-mediated factors to the altered structure and function of alveolar epithelial cells during co-infection with a focus on the 2009 pandemic influenza (pdm2009) and MRSA. Here, we characterized pdm2009 and MRSA replication kinetics, temporal host kinome responses, modulation of MRSA virulence factors, and disruption of alveolar barrier integrity in response to pdm2009-MRSA co-infection. Our results suggest that alveolar barrier disruption during co-infection is mediated primarily through host response dysregulation, resulting in loss of alveolar barrier integrity.",2019 Jan 29,"['Nickol, Michaela E.', 'Ciric, Justine', 'Falcinelli, Shane D.', 'Chertow, Daniel S.', 'Kindrachuk, Jason']",Viruses,,,True
85393cb7a2467599d34d03b28fe6dccd89796f84,PMC,Characterization of Host and Bacterial Contributions to Lung Barrier Dysfunction Following Co-infection with 2009 Pandemic Influenza and Methicillin Resistant Staphylococcus aureus,http://dx.doi.org/10.3390/v11020116,PMC6409999,30699912,CC BY,"Influenza viruses are a threat to global public health resulting in ~500,000 deaths each year. Despite an intensive vaccination program, influenza infections remain a recurrent, yet unsolved public health problem. Secondary bacterial infections frequently complicate influenza infections during seasonal outbreaks and pandemics, resulting in increased morbidity and mortality. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is frequently associated with these co-infections, including the 2009 influenza pandemic. Damage to alveolar epithelium is a major contributor to severe influenza-bacterial co-infections and can result in gas exchange abnormalities, fluid leakage, and respiratory insufficiency. These deleterious manifestations likely involve both pathogen- and host-mediated mechanisms. However, there is a paucity of information regarding the mechanisms (pathogen- and/or host-mediated) underlying influenza-bacterial co-infection pathogenesis. To address this, we characterized the contributions of viral-, bacterial-, and host-mediated factors to the altered structure and function of alveolar epithelial cells during co-infection with a focus on the 2009 pandemic influenza (pdm2009) and MRSA. Here, we characterized pdm2009 and MRSA replication kinetics, temporal host kinome responses, modulation of MRSA virulence factors, and disruption of alveolar barrier integrity in response to pdm2009-MRSA co-infection. Our results suggest that alveolar barrier disruption during co-infection is mediated primarily through host response dysregulation, resulting in loss of alveolar barrier integrity.",2019 Jan 29,"['Nickol, Michaela E.', 'Ciric, Justine', 'Falcinelli, Shane D.', 'Chertow, Daniel S.', 'Kindrachuk, Jason']",Viruses,,,False
724fa0c1969874d0051c6f86795971aab0054c05,PMC,Interferon Regulatory Factor 3-Mediated Signaling Limits Middle-East Respiratory Syndrome (MERS) Coronavirus Propagation in Cells from an Insectivorous Bat,http://dx.doi.org/10.3390/v11020152,PMC6410008,30781790,CC BY,"Insectivorous bats are speculated to be ancestral hosts of Middle-East respiratory syndrome (MERS) coronavirus (CoV). MERS-CoV causes disease in humans with thirty-five percent fatality, and has evolved proteins that counteract human antiviral responses. Since bats experimentally infected with MERS-CoV do not develop signs of disease, we tested the hypothesis that MERS-CoV would replicate less efficiently in bat cells than in human cells because of its inability to subvert antiviral responses in bat cells. We infected human and bat (Eptesicus fuscus) cells with MERS-CoV and observed that the virus grew to higher titers in human cells. MERS-CoV also effectively suppressed the antiviral interferon beta (IFNβ) response in human cells, unlike in bat cells. To determine if IRF3, a critical mediator of the interferon response, also regulated the response in bats, we examined the response of IRF3 to poly(I:C), a synthetic analogue of viral double-stranded RNA. We observed that bat IRF3 responded to poly(I:C) by nuclear translocation and post-translational modifications, hallmarks of IRF3 activation. Suppression of IRF3 by small-interfering RNA (siRNA) demonstrated that IRF3 was critical for poly(I:C) and MERS-CoV induced induction of IFNβ in bat cells. Our study demonstrates that innate antiviral signaling in E. fuscus bat cells is resistant to MERS-CoV-mediated subversion.",2019 Feb 13,"['Banerjee, Arinjay', 'Falzarano, Darryl', 'Rapin, Noreen', 'Lew, Jocelyne', 'Misra, Vikram']",Viruses,,,True
8603258b5adf49597eb2da31925ec9546b42eee7,PMC,Interferon Regulatory Factor 3-Mediated Signaling Limits Middle-East Respiratory Syndrome (MERS) Coronavirus Propagation in Cells from an Insectivorous Bat,http://dx.doi.org/10.3390/v11020152,PMC6410008,30781790,CC BY,"Insectivorous bats are speculated to be ancestral hosts of Middle-East respiratory syndrome (MERS) coronavirus (CoV). MERS-CoV causes disease in humans with thirty-five percent fatality, and has evolved proteins that counteract human antiviral responses. Since bats experimentally infected with MERS-CoV do not develop signs of disease, we tested the hypothesis that MERS-CoV would replicate less efficiently in bat cells than in human cells because of its inability to subvert antiviral responses in bat cells. We infected human and bat (Eptesicus fuscus) cells with MERS-CoV and observed that the virus grew to higher titers in human cells. MERS-CoV also effectively suppressed the antiviral interferon beta (IFNβ) response in human cells, unlike in bat cells. To determine if IRF3, a critical mediator of the interferon response, also regulated the response in bats, we examined the response of IRF3 to poly(I:C), a synthetic analogue of viral double-stranded RNA. We observed that bat IRF3 responded to poly(I:C) by nuclear translocation and post-translational modifications, hallmarks of IRF3 activation. Suppression of IRF3 by small-interfering RNA (siRNA) demonstrated that IRF3 was critical for poly(I:C) and MERS-CoV induced induction of IFNβ in bat cells. Our study demonstrates that innate antiviral signaling in E. fuscus bat cells is resistant to MERS-CoV-mediated subversion.",2019 Feb 13,"['Banerjee, Arinjay', 'Falzarano, Darryl', 'Rapin, Noreen', 'Lew, Jocelyne', 'Misra, Vikram']",Viruses,,,False
d211a9ffb15714958d46365027d61af18c17a269,PMC,Co-Infection of Swine with Porcine Circovirus Type 2 and Other Swine Viruses,http://dx.doi.org/10.3390/v11020185,PMC6410029,30795620,CC BY,"Porcine circovirus 2 (PCV2) is the etiological agent that causes porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD), which are present in every major swine-producing country in the world. PCV2 infections may downregulate the host immune system and enhance the infection and replication of other pathogens. However, the exact mechanisms of PCVD/PCVAD are currently unknown. To date, many studies have reported that several cofactors, such as other swine viruses or bacteria, vaccination failure, and stress or crowding, in combination with PCV2, lead to PCVD/PCVAD. Among these cofactors, co-infection of PCV2 with other viruses, such as porcine reproductive and respiratory syndrome virus, porcine parvovirus, swine influenza virus and classical swine fever virus have been widely studied for decades. In this review, we focus on the current state of knowledge regarding swine co-infection with different PCV2 genotypes or strains, as well as with PCV2 and other swine viruses.",2019 Feb 21,"['Ouyang, Ting', 'Zhang, Xinwei', 'Liu, Xiaohua', 'Ren, Linzhu']",Viruses,,,True
162ffba72e95c4b2686b0b273b47c376aad61ba7,PMC,Myeloid Cells during Viral Infections and Inflammation,http://dx.doi.org/10.3390/v11020168,PMC6410039,30791481,CC BY,"Myeloid cells represent a diverse range of innate leukocytes that are crucial for mounting successful immune responses against viruses. These cells are responsible for detecting pathogen-associated molecular patterns, thereby initiating a signaling cascade that results in the production of cytokines such as interferons to mitigate infections. The aim of this review is to outline recent advances in our knowledge of the roles that neutrophils and inflammatory monocytes play in initiating and coordinating host responses against viral infections. A focus is placed on myeloid cell development, trafficking and antiviral mechanisms. Although known for promoting inflammation, there is a growing body of literature which demonstrates that myeloid cells can also play critical regulatory or immunosuppressive roles, especially following the elimination of viruses. Additionally, the ability of myeloid cells to control other innate and adaptive leukocytes during viral infections situates these cells as key, yet under-appreciated mediators of pathogenic inflammation that can sometimes trigger cytokine storms. The information presented here should assist researchers in integrating myeloid cell biology into the design of novel and more effective virus-targeted therapies.",2019 Feb 19,"['Stegelmeier, Ashley A.', 'van Vloten, Jacob P.', 'Mould, Robert C.', 'Klafuric, Elaine M.', 'Minott, Jessica A.', 'Wootton, Sarah K.', 'Bridle, Byram W.', 'Karimi, Khalil']",Viruses,,,True
3f1d96625c0c358531ba0f8261c930dd6967bd79,PMC,RNA Modifications Modulate Activation of Innate Toll-Like Receptors,http://dx.doi.org/10.3390/genes10020092,PMC6410116,30699960,CC BY,"Self/foreign discrimination by the innate immune system depends on receptors that identify molecular patterns as associated to pathogens. Among others, this group includes endosomal Toll-like receptors, among which Toll-like receptors (TLR) 3, 7, 8, and 13 recognize and discriminate mammalian from microbial, potentially pathogen-associated, RNA. One of the discriminatory principles is the recognition of endogenous RNA modifications. Previous work has identified a couple of RNA modifications that impede activation of TLR signaling when incorporated in synthetic RNA molecules. Of note, work that is more recent has now shown that RNA modifications in their naturally occurring context can have immune-modulatory functions: Gm, a naturally occurring ribose-methylation within tRNA resulted in a lack of TLR7 stimulation and within a defined sequence context acted as antagonist. Additional RNA modifications with immune-modulatory functions have now been identified and recent work also indicates that RNA modifications within the context of whole prokaryotic or eukaryotic cells are indeed used for immune-modulation. This review will discuss new findings and developments in the field of immune-modulatory RNA modifications.",2019 Jan 29,"['Freund, Isabel', 'Eigenbrod, Tatjana', 'Helm, Mark', 'Dalpke, Alexander H.']",Genes (Basel),,,True
28d59a7490b8337301262db257c5cfe98ddede06,PMC,Human Polyclonal Antibodies Produced from Transchromosomal Bovine Provides Prophylactic and Therapeutic Protections Against Zika Virus Infection in STAT2 KO Syrian Hamsters,http://dx.doi.org/10.3390/v11020092,PMC6410148,30678320,CC BY,"Zika virus (ZIKV) infection can cause severe congenital diseases, such as microcephaly, ocular defects and arthrogryposis in fetuses, and Guillain–Barré syndrome in adults. Efficacious therapeutic treatments for infected patients, as well as prophylactic treatments to prevent new infections are needed for combating ZIKV infection. Here, we report that ZIKV-specific human polyclonal antibodies (SAB-155), elicited in transchromosomal bovine (TcB), provide significant protection from infection by ZIKV in STAT2 knockout (KO) golden Syrian hamsters both prophylactically and therapeutically. These antibodies also prevent testicular lesions in this hamster model. Our data indicate that antibody-mediated immunotherapy is effective in treating ZIKV infection. Because suitable quantities of highly potent human polyclonal antibodies can be quickly produced from the TcB system against ZIKV and have demonstrated therapeutic efficacy in a small animal model, they have the potential as an effective countermeasure against ZIKV infection.",2019 Jan 22,"['Siddharthan, Venkatraman', 'Miao, Jinxin', 'Van Wettere, Arnaud J', 'Li, Rong', 'Wu, Hua', 'Sullivan, Eddie', 'Jiao, Jinan', 'Hooper, Jay W.', 'Safronetz, David', 'Morrey, John D.', 'Julander, Justin G.', 'Wang, Zhongde']",Viruses,,,True
8bf3d561863300dbcb9ba92ad94807dfb8775f7a,PMC,Antiviral Drug Discovery: Norovirus Proteases and Development of Inhibitors,http://dx.doi.org/10.3390/v11020197,PMC6410195,30823509,CC BY,"Proteases are a major enzyme group playing important roles in a wide variety of biological processes in life forms ranging from viruses to mammalians. The aberrant activity of proteases can lead to various diseases; consequently, host proteases have been the focus of intense investigation as potential therapeutic targets. A wide range of viruses encode proteases which play an essential role in viral replication and, therefore, constitute attractive targets for the development of antiviral therapeutics. There are numerous examples of successful drug development targeting cellular and viral proteases, including antivirals against human immunodeficiency virus and hepatitis C virus. Most FDA-approved antiviral agents are peptidomimetics and macrocyclic compounds that interact with the active site of a targeted protease. Norovirus proteases are cysteine proteases that contain a chymotrypsin-like fold in their 3D structures. This review focuses on our group’s efforts related to the development of norovirus protease inhibitors as potential anti-norovirus therapeutics. These protease inhibitors are rationally designed transition-state inhibitors encompassing dipeptidyl, tripeptidyl and macrocyclic compounds. Highly effective inhibitors validated in X-ray co-crystallization, enzyme and cell-based assays, as well as an animal model, were generated by launching an optimization campaign utilizing the initial hit compounds. A prodrug approach was also explored to improve the pharmacokinetics (PK) of the identified inhibitors.",2019 Feb 25,"['Chang, Kyeong-Ok', 'Kim, Yunjeong', 'Lovell, Scott', 'Rathnayake, Athri D.', 'Groutas, William C.']",Viruses,,,True
3e5e8609bc2b23b770b037ee006b028a17f4a121,PMC,Immune System Modulation and Viral Persistence in Bats: Understanding Viral Spillover,http://dx.doi.org/10.3390/v11020192,PMC6410205,30813403,CC BY,Bats harbor a myriad of viruses and some of these viruses may have spilled over to other species including humans. Spillover events are rare and several factors must align to create the “perfect storm” that would ultimately lead to a spillover. One of these factors is the increased shedding of virus by bats. Several studies have indicated that bats have unique defense mechanisms that allow them to be persistently or latently infected with viruses. Factors leading to an increase in the viral load of persistently infected bats would facilitate shedding of virus. This article reviews the unique nature of bat immune defenses that regulate virus replication and the various molecular mechanisms that play a role in altering the balanced bat–virus relationship.,2019 Feb 23,"['Subudhi, Sonu', 'Rapin, Noreen', 'Misra, Vikram']",Viruses,,,True
f781ae4966ab37b3cc7cf282c732db401856870b,PMC,"A New Genotype of Feline Morbillivirus Infects Primary Cells of the Lung, Kidney, Brain and Peripheral Blood",http://dx.doi.org/10.3390/v11020146,PMC6410220,30744110,CC BY,"Paramyxoviruses comprise a large number of diverse viruses which in part give rise to severe diseases in affected hosts. A new genotype of feline morbillivirus, tentatively named feline morbillivirus genotype 2 (FeMV-GT2), was isolated from urine of cats with urinary tract diseases. Whole genome sequencing showed about 78% nucleotide homology to known feline morbilliviruses. The virus was isolated in permanent cell lines of feline and simian origin. To investigate the cell tropism of FeMV-GT2 feline primary epithelial cells from the kidney, the urinary bladder and the lung, peripheral blood mononuclear cells (PBMC), as well as organotypic brain slice cultures were used for infection experiments. We demonstrate that FeMV-GT2 is able to infect renal and pulmonary epithelial cells, primary cells from the cerebrum and cerebellum, as well as immune cells in the blood, especially CD4(+) T cells, CD20(+) B cells and monocytes. The cats used for virus isolation shed FeMV-GT2 continuously for several months despite the presence of neutralizing antibodies in the blood. Our results point towards the necessity of increased awareness for this virus when clinical signs of the aforementioned organs are encountered in cats which cannot be explained by other etiologies.",2019 Feb 9,"['Sieg, Michael', 'Busch, Johannes', 'Eschke, Maria', 'Böttcher, Denny', 'Heenemann, Kristin', 'Vahlenkamp, Annett', 'Reinert, Anja', 'Seeger, Johannes', 'Heilmann, Romy', 'Scheffler, Kira', 'Vahlenkamp, Thomas W.']",Viruses,,,True
bb2c8c79dafcc25bcd68644bf23a4a368bcbd01a,PMC,"A New Genotype of Feline Morbillivirus Infects Primary Cells of the Lung, Kidney, Brain and Peripheral Blood",http://dx.doi.org/10.3390/v11020146,PMC6410220,30744110,CC BY,"Paramyxoviruses comprise a large number of diverse viruses which in part give rise to severe diseases in affected hosts. A new genotype of feline morbillivirus, tentatively named feline morbillivirus genotype 2 (FeMV-GT2), was isolated from urine of cats with urinary tract diseases. Whole genome sequencing showed about 78% nucleotide homology to known feline morbilliviruses. The virus was isolated in permanent cell lines of feline and simian origin. To investigate the cell tropism of FeMV-GT2 feline primary epithelial cells from the kidney, the urinary bladder and the lung, peripheral blood mononuclear cells (PBMC), as well as organotypic brain slice cultures were used for infection experiments. We demonstrate that FeMV-GT2 is able to infect renal and pulmonary epithelial cells, primary cells from the cerebrum and cerebellum, as well as immune cells in the blood, especially CD4(+) T cells, CD20(+) B cells and monocytes. The cats used for virus isolation shed FeMV-GT2 continuously for several months despite the presence of neutralizing antibodies in the blood. Our results point towards the necessity of increased awareness for this virus when clinical signs of the aforementioned organs are encountered in cats which cannot be explained by other etiologies.",2019 Feb 9,"['Sieg, Michael', 'Busch, Johannes', 'Eschke, Maria', 'Böttcher, Denny', 'Heenemann, Kristin', 'Vahlenkamp, Annett', 'Reinert, Anja', 'Seeger, Johannes', 'Heilmann, Romy', 'Scheffler, Kira', 'Vahlenkamp, Thomas W.']",Viruses,,,False
a799d4baa0f252468dcbeaa466fbed7736bf20c5,PMC,Enhanced Ability of Oligomeric Nanobodies Targeting MERS Coronavirus Receptor-Binding Domain,http://dx.doi.org/10.3390/v11020166,PMC6410414,30791410,CC BY,"Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV), an infectious coronavirus first reported in 2012, has a mortality rate greater than 35%. Therapeutic antibodies are key tools for preventing and treating MERS-CoV infection, but to date no such agents have been approved for treatment of this virus. Nanobodies (Nbs) are camelid heavy chain variable domains with properties distinct from those of conventional antibodies and antibody fragments. We generated two oligomeric Nbs by linking two or three monomeric Nbs (Mono-Nbs) targeting the MERS-CoV receptor-binding domain (RBD), and compared their RBD-binding affinity, RBD–receptor binding inhibition, stability, and neutralizing and cross-neutralizing activity against MERS-CoV. Relative to Mono-Nb, dimeric Nb (Di-Nb) and trimeric Nb (Tri-Nb) had significantly greater ability to bind MERS-CoV RBD proteins with or without mutations in the RBD, thereby potently blocking RBD–MERS-CoV receptor binding. The engineered oligomeric Nbs were very stable under extreme conditions, including low or high pH, protease (pepsin), chaotropic denaturant (urea), and high temperature. Importantly, Di-Nb and Tri-Nb exerted significantly elevated broad-spectrum neutralizing activity against at least 19 human and camel MERS-CoV strains isolated in different countries and years. Overall, the engineered Nbs could be developed into effective therapeutic agents for prevention and treatment of MERS-CoV infection.",2019 Feb 19,"['He, Lei', 'Tai, Wanbo', 'Li, Jiangfan', 'Chen, Yuehong', 'Gao, Yaning', 'Li, Junfeng', 'Sun, Shihui', 'Zhou, Yusen', 'Du, Lanying', 'Zhao, Guangyu']",Viruses,,,True
2468815380ef0da6656eafec81936b459b5b210e,PMC,"No-Notice Mystery Patient Drills to Assess Emergency Preparedness for Infectious Diseases at Community Health Centers in New York City, 2015–2016",http://dx.doi.org/10.1007/s10900-018-00595-5,PMC6411664,30604224,CC BY,"Mystery patient drills using simulated patients have been used in hospitals to assess emergency preparedness for infectious diseases, but these drills have seldom been reported in primary care settings. We conducted three rounds of mystery patient drills designed to simulate either influenza-like illness (ILI) or measles at 41 community health centers in New York City from April 2015 through December 2016. Among 50 drills conducted, 49 successfully screened the patient–actor (defined as provision of a mask or referral to the medical team given concern of infection requiring potential isolation), with 35 (70%) drills completing screening without any challenges. In 47 drills, the patient was subsequently isolated (defined as placement in a closed room to limit transmission), with 29 (58%) drills completing isolation without any challenges. Patient–actors simulating ILI were more likely to be masked than those simulating measles (93% vs. 59%, p = 0.007). Median time to screening was 2 min (interquartile range [IQR] 2–6 min) and subsequently to isolation was 1 min (IQR 0–2 min). Approximately 95% of participants reported the drill was realistic and prepared them to deal with the hazards addressed. Qualitative analysis revealed recurring themes for strengths (e.g., established protocols, effective communication) and areas for improvement (e.g., hand hygiene, explaining isolation rationale). We conclude that mystery patient drills are an effective and feasible longitudinal collaboration between health departments and primary care clinics to assess and inform emergency preparedness for infectious diseases.",2019 Jan 2,"['Ali, Mohsin', 'Williams, Marsha D.']",J Community Health,,,True
42d1823428c311725c7395123a3c2c276b7b5fd1,PMC,Application of Duplex Fluorescence Melting Curve Analysis (FMCA) to Identify Canine Parvovirus Type 2 Variants,http://dx.doi.org/10.3389/fmicb.2019.00419,PMC6411689,30891024,CC BY,"Canine parvovirus (CPV-2) is an enteric virus causing morbidity and mortality in dogs worldwide. Since CPV-2 emerged as canine pathogen, the original CPV-2 strain has constantly evolved, and its primary variants (CPV-2a, CPV-2b, and CPV-2c) co-circulate to varying extents in canine populations worldwide. Thus, rapid and accurate laboratory diagnoses of CPV-2 variants are crucial to monitor CPV-2 evolution. Conventional methods for CPV-2 genotyping are laborious, time consuming, and determining the genotype of a CPV-2 variant often requires two or more reaction tubes. The present study developed a probe-based fluorescence melting curve analysis (FMCA) for genotyping six different CPV-2 variants (original CPV-2, CPV-2a, CPV-2b, CPV-2c, and vaccine strains of CPVpf and CPVint) in a single reaction tube using only two TaqMan probes. One of the TaqMan probes (FAM labeled) was designed to perfectly match with the target sequence of CPV-2a, this probe allows a 1-bp mismatched hybridization with the CPV-2b VP2 gene region (A4062G), and a 2-bp mismatched hybridization for CPV-2c (A4062G and T4064A); Another TaqMan probe (HEX labeled) was produced to perfectly match with the target sequence of original CPV-2, this probe enables 1-bp mismatched hybridization with the other CPV-2 variants (A3045T). Using the two TaqMan probes, all six CPV-2 variants were readily distinguished by their respective melting temperature values in a single reaction tube. The detection limits of this assay were 1–10 copies per reaction for six CPV-2 construction plasmids and no cross reactions were observed with several other common canine viruses. In this assay, co-infected samples were also directly identified via probe-based FMCA without using a mixing control; only a pure control is required. The clinical evaluation of this assay was demonstrated by analyzing 83 clinical fecal samples, among which 41 (49.39%), 8 (9.63%), and 14 (16.87%) samples were found to be positive for CPV-2a, CPV-2b, and CPV-2c, respectively. The concordance rate between probe-based FMCA and Sanger sequencing was 100%. Thus, the duplex FMCA is effective, rapid, simple, high-throughput, and straightforward for genotyping CPV-2 variants, and is useful to effectively diagnose and monitor CPV-2 epidemiology.",2019 Mar 5,"['Liu, Zhicheng', 'Bingga, Gali', 'Zhang, Chunhong', 'Shao, Junjie', 'Shen, Haiyan', 'Sun, Junying', 'Zhang, Jianfeng']",Front Microbiol,,,True
286ffc3b37fa763b765bb3d8403fd4deacff80c3,PMC,Free Fatty Acids’ Level and Nutrition in Critically Ill Patients and Association with Outcomes: A Prospective Sub-Study of PermiT Trial,http://dx.doi.org/10.3390/nu11020384,PMC6412238,30781774,CC BY,"Objectives: The objectives of this study were to evaluate the clinical and nutritional correlates of high free fatty acids (FFAs) level in critically ill patients and the association with outcomes, and to study the effect of short-term caloric restriction (permissive underfeeding) on FFAs level during critical illness. Patients/Method: In this pre-planned sub-study of the PermiT (Permissive Underfeeding vs. Target Enteral Feeding in Adult Critically Ill Patients) trial, we included critically ill patients who were expected to stay for ≥14 days in the intensive care unit. We measured FFAs level on day 1, 3, 5, 7, and 14 of enrollment. Of 70 enrolled patients, 23 (32.8%) patients had high FFAs level (baseline FFAs level >0.45 mmol/L in females and >0.6 mmol/L in males). Results: Patients with high FFAs level were significantly older and more likely to be females and diabetics and they had lower ratio of partial pressure of oxygen to the fraction of inspired oxygen, higher creatinine, and higher total cholesterol levels than those with normal FFAs level. During the study period, patients with high FFAs level had higher blood glucose and required more insulin. On multivariable logistic regression analysis, the predictors of high baseline FFAs level were diabetes (adjusted odds ratio (aOR): 5.36; 95% confidence interval (CI): 1.56, 18.43, p = 0.008) and baseline cholesterol level (aOR, 4.29; 95% CI: 11.64, 11.19, p = 0.003). Serial levels of FFAs did not differ with time between permissive underfeeding and standard feeding groups. FFAs level was not associated with 90-day mortality (aOR: 0.49; 95% CI: 0.09, 2.60, p = 0.40). Conclusion: We conclude that high FFAs level in critically ill patients is associated with features of metabolic syndrome and is not affected by short-term permissive underfeeding.",2019 Feb 13,"['Arabi, Yaseen M.', 'Tamimi, Waleed', 'Jones, Gwynne', 'Jawdat, Dunia', 'Tamim, Hani', 'Al-Dorzi, Hasan M.', 'Sadat, Musharaf', 'Afesh, Lara', 'Sakhija, Maram', 'Al-Dawood, Abdulaziz']",Nutrients,,,True
b2cdaca8c71ad1e78c0fbb7d00c5145a00928f12,PMC,Free Fatty Acids’ Level and Nutrition in Critically Ill Patients and Association with Outcomes: A Prospective Sub-Study of PermiT Trial,http://dx.doi.org/10.3390/nu11020384,PMC6412238,30781774,CC BY,"Objectives: The objectives of this study were to evaluate the clinical and nutritional correlates of high free fatty acids (FFAs) level in critically ill patients and the association with outcomes, and to study the effect of short-term caloric restriction (permissive underfeeding) on FFAs level during critical illness. Patients/Method: In this pre-planned sub-study of the PermiT (Permissive Underfeeding vs. Target Enteral Feeding in Adult Critically Ill Patients) trial, we included critically ill patients who were expected to stay for ≥14 days in the intensive care unit. We measured FFAs level on day 1, 3, 5, 7, and 14 of enrollment. Of 70 enrolled patients, 23 (32.8%) patients had high FFAs level (baseline FFAs level >0.45 mmol/L in females and >0.6 mmol/L in males). Results: Patients with high FFAs level were significantly older and more likely to be females and diabetics and they had lower ratio of partial pressure of oxygen to the fraction of inspired oxygen, higher creatinine, and higher total cholesterol levels than those with normal FFAs level. During the study period, patients with high FFAs level had higher blood glucose and required more insulin. On multivariable logistic regression analysis, the predictors of high baseline FFAs level were diabetes (adjusted odds ratio (aOR): 5.36; 95% confidence interval (CI): 1.56, 18.43, p = 0.008) and baseline cholesterol level (aOR, 4.29; 95% CI: 11.64, 11.19, p = 0.003). Serial levels of FFAs did not differ with time between permissive underfeeding and standard feeding groups. FFAs level was not associated with 90-day mortality (aOR: 0.49; 95% CI: 0.09, 2.60, p = 0.40). Conclusion: We conclude that high FFAs level in critically ill patients is associated with features of metabolic syndrome and is not affected by short-term permissive underfeeding.",2019 Feb 13,"['Arabi, Yaseen M.', 'Tamimi, Waleed', 'Jones, Gwynne', 'Jawdat, Dunia', 'Tamim, Hani', 'Al-Dorzi, Hasan M.', 'Sadat, Musharaf', 'Afesh, Lara', 'Sakhija, Maram', 'Al-Dawood, Abdulaziz']",Nutrients,,,False
4a34c342ffd1ba52c4539dab0d2ccce00bfb8517,PMC,Role of p90RSK in Kidney and Other Diseases,http://dx.doi.org/10.3390/ijms20040972,PMC6412535,30813401,CC BY,"The 90 kDa ribosomal s6 kinases (RSKs) are a group of serine/threonine kinases consisting of 4 RSK isoforms (RSK1-4), of which RSK1 is also designated as p90RSK. p90RSK plays an important role in the Ras-mitogen-activated protein kinase (MAPK) signalling cascade and is the direct downstream effector of Ras-extracellular signal-regulated kinase (ERK1/2) signalling. ERK1/2 activation directly phosphorylates and activates p90RSK, which, in turn, activates various signalling events through selection of different phosphorylation substrates. Upregulation of p90RSK has been reported in numerous human diseases. p90RSK plays an important role in the regulation of diverse cellular processes. Thus, aberrant activation of p90RSK plays a critical role in the pathogenesis of organ dysfunction and damage. In this review, we focus on the current understanding of p90RSK functions and roles in the development and progression of kidney diseases. Roles of p90RSK, as well as other RSKs, in cardiovascular disorders and cancers are also discussed.",2019 Feb 23,"['Lin, Ling', 'White, Samantha A.', 'Hu, Kebin']",Int J Mol Sci,,,True
74c453c26b6159ac06a950e978525cd585cf3e5c,PMC,Quality Screening of Incorrectly Folded Soluble Aggregates from Functional Recombinant Proteins,http://dx.doi.org/10.3390/ijms20040907,PMC6413200,30791505,CC BY,"Solubility is the prime criterion for determining the quality of recombinant proteins, yet it often fails to represent functional activity due to the involvement of non-functional, misfolded, soluble aggregates, which compromise the quality of recombinant proteins. However, guidelines for the quality assessment of soluble proteins have neither been proposed nor rigorously validated experimentally. Using the aggregation-prone enhanced green-fluorescent protein (EGFP) folding reporter system, we evaluated the folding status of recombinant proteins by employing the commonly used sonication and mild lysis of recombinant host cells. We showed that the differential screening of solubility and folding competence is crucial for improving the quality of recombinant proteins without sacrificing their yield. These results highlight the importance of screening out incorrectly folded soluble aggregates at the initial purification step to ensure the functional quality of recombinant proteins.",2019 Feb 19,"['Kwon, Soon Bin', 'Yu, Ji Eun', 'Kim, Jihoon', 'Oh, Hana', 'Park, Chan', 'Lee, Jinhee', 'Seong, Baik L.']",Int J Mol Sci,,,True
7f7e7b0bb3f8e89fed253891b5632236d20a4cb7,PMC,Appropriate scaling approach for evaluating peak VO(2) development in Southern Chinese 8 to 16 years old,http://dx.doi.org/10.1371/journal.pone.0213674,PMC6413916,30861055,CC BY,"OBJECTIVE: To investigate scaling approaches for evaluating the development of peak VO(2) and improving the identification of low cardiopulmonary fitness in Southern Chinese children and adolescents. METHODS: Nine hundred and twenty Chinese children and adolescents (8 to 16 years) underwent graded cardiopulmonary exercise test on a treadmill until volitional exhaustion. Peak VO(2) was corrected for the effects of body mass by ratio or allometric scaling. Z score equations for predicting peak VO(2) were developed. Correlations between scaled peak VO(2), z scores, body size and age were tested to examine the effectiveness of the approach. RESULTS: Eight hundred and fifty-two participants (48% male) were included in the analyses. Absolute peak VO(2) significantly increased with age in both sexes (both P<0.05), while ratio-scaled peak VO(2) increased only in males (P<0.05). Allometrically scaled peak VO(2) increased from 11 years in both sexes, plateauing by 12 years in girls and continuing to rise until 15 years in boys. Allometically scaled peak VO(2) was not correlated with body mass, but remained correlated with height and age in all but the older girls. Peak VO(2) z score was not correlated with body mass, height or age. CONCLUSIONS: Absolute and allometric scaled peak VO(2) values are provided for Hong Kong Chinese children and adolescents by age and sex. Peak VO(2) z scores improve the evaluation of cardiopulmonary fitness, allowing comparisons across ages and sex and will likely provide a better metric for tracking change over time in children and adolescents, regardless of body size and age.",2019 Mar 12,"['Yu, Clare C. W.', 'McManus, Ali M.', 'Au, Chun T.', 'So, Hung K.', 'Chan, Adrienne', 'Sung, Rita Y. T.', 'Li, Albert M.']",PLoS One,,,True
98361da4984090561a6e9c374b9a782b53cfda5f,PMC,"Influenza C virus in pre-school children with respiratory infections: retrospective analysis of data from the national influenza surveillance system in Germany, 2012 to 2014",http://dx.doi.org/10.2807/1560-7917.ES.2019.24.10.1800174,PMC6415498,30862333,CC BY,"INTRODUCTION: Recent data on influenza C virus indicate a possible higher clinical impact in specified patient populations than previously thought. AIM: We aimed to investigate influenza C virus circulation in Germany. METHODS: A total of 1,588 samples from 0 to 4 year-old children presenting as outpatients with influenza-like illness (ILI) or acute respiratory infection were analysed retrospectively. The samples represented a subset of all samples from the German national surveillance system for influenza in this age group in 2012–14. The presence of influenza C virus was investigated by real-time PCR. For positive samples, information on symptoms as well as other respiratory virus co-infections was considered. Retrieved influenza C viral sequences were phylogenetically characterised. RESULTS: Influenza C viral RNA was detected in 20 (1.3% of) samples, including 16 during the 2012/13 season. The majority (18/20) of influenza C-positive patients had ILI according to the European Union definition, one patient had pneumonia. Viruses belonged to the C/Sao Paulo and C/Kanagawa lineages. Most (11/20) samples were co-infected with other respiratory viruses. CONCLUSION: Our data are the first on influenza C virus circulation in Germany and notably from a European national surveillance system. The low detection frequency and the identified virus variants confirm earlier observations outside a surveillance system. More virus detections during the 2012/13 season indicate a variable circulation intensity in the different years studied. Influenza C virus can be considered for ILI patients. Future studies addressing its clinical impact, especially in patients with severe disease are needed.",2019 Mar 7,"['Fritsch, Annemarie', 'Schweiger, Brunhilde', 'Biere, Barbara']",Euro Surveill,,,False
4a316d8ac91890d174943234ececeb61115be216,PMC,"Influenza C virus in pre-school children with respiratory infections: retrospective analysis of data from the national influenza surveillance system in Germany, 2012 to 2014",http://dx.doi.org/10.2807/1560-7917.ES.2019.24.10.1800174,PMC6415498,30862333,CC BY,"INTRODUCTION: Recent data on influenza C virus indicate a possible higher clinical impact in specified patient populations than previously thought. AIM: We aimed to investigate influenza C virus circulation in Germany. METHODS: A total of 1,588 samples from 0 to 4 year-old children presenting as outpatients with influenza-like illness (ILI) or acute respiratory infection were analysed retrospectively. The samples represented a subset of all samples from the German national surveillance system for influenza in this age group in 2012–14. The presence of influenza C virus was investigated by real-time PCR. For positive samples, information on symptoms as well as other respiratory virus co-infections was considered. Retrieved influenza C viral sequences were phylogenetically characterised. RESULTS: Influenza C viral RNA was detected in 20 (1.3% of) samples, including 16 during the 2012/13 season. The majority (18/20) of influenza C-positive patients had ILI according to the European Union definition, one patient had pneumonia. Viruses belonged to the C/Sao Paulo and C/Kanagawa lineages. Most (11/20) samples were co-infected with other respiratory viruses. CONCLUSION: Our data are the first on influenza C virus circulation in Germany and notably from a European national surveillance system. The low detection frequency and the identified virus variants confirm earlier observations outside a surveillance system. More virus detections during the 2012/13 season indicate a variable circulation intensity in the different years studied. Influenza C virus can be considered for ILI patients. Future studies addressing its clinical impact, especially in patients with severe disease are needed.",2019 Mar 7,"['Fritsch, Annemarie', 'Schweiger, Brunhilde', 'Biere, Barbara']",Euro Surveill,,,False
e1f6b17bdd06ae44978e5359fbe7df68ac5fa1cf,PMC,"Influenza C virus in pre-school children with respiratory infections: retrospective analysis of data from the national influenza surveillance system in Germany, 2012 to 2014",http://dx.doi.org/10.2807/1560-7917.ES.2019.24.10.1800174,PMC6415498,30862333,CC BY,"INTRODUCTION: Recent data on influenza C virus indicate a possible higher clinical impact in specified patient populations than previously thought. AIM: We aimed to investigate influenza C virus circulation in Germany. METHODS: A total of 1,588 samples from 0 to 4 year-old children presenting as outpatients with influenza-like illness (ILI) or acute respiratory infection were analysed retrospectively. The samples represented a subset of all samples from the German national surveillance system for influenza in this age group in 2012–14. The presence of influenza C virus was investigated by real-time PCR. For positive samples, information on symptoms as well as other respiratory virus co-infections was considered. Retrieved influenza C viral sequences were phylogenetically characterised. RESULTS: Influenza C viral RNA was detected in 20 (1.3% of) samples, including 16 during the 2012/13 season. The majority (18/20) of influenza C-positive patients had ILI according to the European Union definition, one patient had pneumonia. Viruses belonged to the C/Sao Paulo and C/Kanagawa lineages. Most (11/20) samples were co-infected with other respiratory viruses. CONCLUSION: Our data are the first on influenza C virus circulation in Germany and notably from a European national surveillance system. The low detection frequency and the identified virus variants confirm earlier observations outside a surveillance system. More virus detections during the 2012/13 season indicate a variable circulation intensity in the different years studied. Influenza C virus can be considered for ILI patients. Future studies addressing its clinical impact, especially in patients with severe disease are needed.",2019 Mar 7,"['Fritsch, Annemarie', 'Schweiger, Brunhilde', 'Biere, Barbara']",Euro Surveill,,,True
1ac9aac4ecdf40363f1377cc08484db3dc4abf93,PMC,Evaluation of the Serologic Cross-Reactivity between Transmissible Gastroenteritis Coronavirus and Porcine Respiratory Coronavirus Using Commercial Blocking Enzyme-Linked Immunosorbent Assay Kits,http://dx.doi.org/10.1128/mSphere.00017-19,PMC6416363,30867325,CC BY,"This study compared the performances of three commercial transmissible gastroenteritis virus/porcine respiratory coronavirus (TGEV/PRCV) blocking enzyme-linked immunosorbent assays (ELISAs) using serum samples (n = 528) collected over a 49-day observation period from pigs inoculated with TGEV strain Purdue (n = 12), TGEV strain Miller (n = 12), PRCV (n = 12), or with virus-free culture medium (n = 12). ELISA results were evaluated both with “suspect” results interpreted as positive and then as negative. All commercial kits showed excellent diagnostic specificity (99 to 100%) when testing samples from pigs inoculated with virus-free culture medium. However, analyses revealed differences between the kits in diagnostic sensitivity (percent TGEV- or PRCV-seropositive pigs), and all kits showed significant (P < 0.05) cross-reactivity between TGEV and PRCV serum antibodies, particularly during early stages of the infections. Serologic cross-reactivity between TGEV and PRCV seemed to be TGEV strain dependent, with a higher percentage of PRCV-false-positive results for pigs inoculated with TGEV Purdue than for TGEV Miller. Moreover, the overall proportion of false positives was higher when suspect results were interpreted as positive, regardless of the ELISA kit evaluated. IMPORTANCE Current measures to prevent TGEV from entering a naive herd include quarantine and testing for TGEV-seronegative animals. However, TGEV serology is complicated due to the cross-reactivity with PRCV, which circulates subclinically in most swine herds worldwide. Conventional serological tests cannot distinguish between TGEV and PRCV antibodies; however, blocking ELISAs using antigen containing a large deletion in the amino terminus of the PRCV S protein permit differentiation of PRCV and TGEV antibodies. Several commercial TGEV/PRCV blocking ELISAs are available, but performance comparisons have not been reported in recent research. This study demonstrates that the serologic cross-reactivity between TGEV and PRCV affects the accuracy of commercial blocking ELISAs. Individual test results must be interpreted with caution, particularly in the event of suspect results. Therefore, commercial TGEV/PRCV blocking ELISAs should only be applied on a herd basis.",2019 Mar 13,"['Magtoto, Ronaldo', 'Poonsuk, Korakrit', 'Baum, David', 'Zhang, Jianqiang', 'Chen, Qi', 'Ji, Ju', 'Piñeyro, Pablo', 'Zimmerman, Jeffrey', 'Giménez-Lirola, Luis G.']",mSphere,,,True
f0bfdb9e577ba15d0faead04d23b7e0ffca4a701,PMC,Capacity building in health care professions within the Gulf cooperation council countries: paving the way forward,http://dx.doi.org/10.1186/s12909-019-1513-2,PMC6417223,30871521,CC BY,"BACKGROUND: There is a worldwide shortage of health care workers. This problem is particularly severe in the Gulf Cooperation Council (GCC) countries because of shortages in certain medical disciplines, due to a lack of nationally-trained professionals and a less developed educational system compared to other high income countries. Consequently, GCC countries are heavily dependent on an expatriate health care workforce; a problem exacerbated by high turnover. We discuss challenges and potential strategies for improving and strengthening capacity building efforts in health care professions in the GCC. MAIN TEXT: In the GCC, there are 139 schools providing professional health education in medicine, dentistry, pharmacy, nursing, midwifery, and other specialties. Health education school density reported for the GCC countries ranges between 2.2 and 2.8 schools per one million inhabitants, except in Oman where it is 4.0 per one million inhabitants. The GCC countries rely heavily on expatriate health professionals. The number of physicians and nurses in the GCC countries are 2.1 and 4.5 per 1000 respectively, compared to 2.8 and 7.9 among member countries of the Organisation for Economic Cooperation and Development (OECD). Interestingly, the number of dentists and pharmacists is higher in the GCC countries compared to OECD countries. A nationally trained health care workforce is essential for the GCC countries. Physiotherapy and occupational therapy are two identified areas where growth and development are recommended. Custom-tailored continuing medical education and continuing professional development (CPD) programs can augment the skills of health practitioners, and allow for the expansion of their scope of practice when warranted. CONCLUSION: Capacity building can play an essential role in addressing the major health challenges and improving the overall quality of health care in the region. Efforts aimed at increasing the number of locally-trained graduates and developing and implementing need-based CPD programs are vital for capacity building and lifelong learning in health care professions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12909-019-1513-2) contains supplementary material, which is available to authorized users.",2019 Mar 14,"['Sheikh, Javaid I.', 'Cheema, Sohaila', 'Chaabna, Karima', 'Lowenfels, Albert B.', 'Mamtani, Ravinder']",BMC Med Educ,,,False
2e87670d524b1b76e2af6090d5cba472a6448f85,PMC,Capacity building in health care professions within the Gulf cooperation council countries: paving the way forward,http://dx.doi.org/10.1186/s12909-019-1513-2,PMC6417223,30871521,CC BY,"BACKGROUND: There is a worldwide shortage of health care workers. This problem is particularly severe in the Gulf Cooperation Council (GCC) countries because of shortages in certain medical disciplines, due to a lack of nationally-trained professionals and a less developed educational system compared to other high income countries. Consequently, GCC countries are heavily dependent on an expatriate health care workforce; a problem exacerbated by high turnover. We discuss challenges and potential strategies for improving and strengthening capacity building efforts in health care professions in the GCC. MAIN TEXT: In the GCC, there are 139 schools providing professional health education in medicine, dentistry, pharmacy, nursing, midwifery, and other specialties. Health education school density reported for the GCC countries ranges between 2.2 and 2.8 schools per one million inhabitants, except in Oman where it is 4.0 per one million inhabitants. The GCC countries rely heavily on expatriate health professionals. The number of physicians and nurses in the GCC countries are 2.1 and 4.5 per 1000 respectively, compared to 2.8 and 7.9 among member countries of the Organisation for Economic Cooperation and Development (OECD). Interestingly, the number of dentists and pharmacists is higher in the GCC countries compared to OECD countries. A nationally trained health care workforce is essential for the GCC countries. Physiotherapy and occupational therapy are two identified areas where growth and development are recommended. Custom-tailored continuing medical education and continuing professional development (CPD) programs can augment the skills of health practitioners, and allow for the expansion of their scope of practice when warranted. CONCLUSION: Capacity building can play an essential role in addressing the major health challenges and improving the overall quality of health care in the region. Efforts aimed at increasing the number of locally-trained graduates and developing and implementing need-based CPD programs are vital for capacity building and lifelong learning in health care professions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12909-019-1513-2) contains supplementary material, which is available to authorized users.",2019 Mar 14,"['Sheikh, Javaid I.', 'Cheema, Sohaila', 'Chaabna, Karima', 'Lowenfels, Albert B.', 'Mamtani, Ravinder']",BMC Med Educ,,,True
b2e781c81e340e91a0f27009b29d0c8a3635c5e8,PMC,"Evaluation of the sentinel surveillance system for influenza-like illnesses in the Greater Accra region, Ghana, 2018",http://dx.doi.org/10.1371/journal.pone.0213627,PMC6417674,30870489,CC BY,"BACKGROUND: Influenza-like Illness (ILI) is a medical diagnosis of possible influenza or another respiratory illness with a common set of symptoms. The deaths of four schoolchildren, during a pandemic influenza outbreak in December 2017 in Ghana, raised doubts about the ILI surveillance system’s performance. We evaluated the ILI surveillance system in the Greater Accra region, Ghana, to assess the system’s attributes and its performance on set objectives. METHODS: CDC guidelines were used to evaluate the data of the ILI surveillance system between 2013 and 2017. We interviewed the surveillance personnel on the system’s description and operation. Additionally, routinely entered ILI data from the National Influenza Center provided by the six sentinel sites in Accra was extracted. We sampled and reviewed 120 ILI case-investigation forms from these sites. Surveillance activities were examined on system’s performance indicators, each being scored on a scale of 1 to 3 (poorest to best performance). RESULTS: All population and age groups were under ILI surveillance over the period evaluated. Overall, 2948 suspected case-patients, including 392 (13.3%) children under-five were reported, with 219 being positive for influenza virus (Predictive value positive = 7.4%). The predominant influenza subtype was H3N2, recorded in 90 (41.1%) of positive case-patients. The system only met two out of its four objectives. None of the six sentinel sites consistently met their annual 260 suspected case-detection quota. Samples reached the laboratory on average 48 hours after collection and results were disseminated within 7 days. Of 120 case-investigation forms sampled, 91 (76.3%) were completely filled in. CONCLUSIONS: The ILI surveillance system in the Greater Accra region is only partially meeting its objectives. While it is found to be sensitive, representative and timely, the data quality was sub-optimal. We recommend the determination of thresholds for alert and outbreak detection and ensuring that sentinel sites meet their weekly case-detection targets.",2019 Mar 14,"['Nuvey, Francis Sena', 'Edu-Quansah, Elijah Paa', 'Kuma, George Khumalo', 'Eleeza, John', 'Kenu, Ernest', 'Sackey, Samuel', 'Ameme, Donne', 'Abakar, Mahamat Fayiz', 'Kreppel, Katharina', 'Ngandolo, Richard Bongo', 'Afari, Edwin', 'Bonfoh, Bassirou']",PLoS One,,,True
2aba8ab7cfc9ae8cdefcadc254b5a815a3373c87,PMC,Predictors of Initial Smear-Negative Active Pulmonary Tuberculosis with Acute Early Stage Lung Injury by High-Resolution Computed Tomography and Clinical Manifestations: An Auxiliary Model in Critical Patients,http://dx.doi.org/10.1038/s41598-019-40799-w,PMC6418143,30872774,CC BY,"This study evaluated the diagnostic use of high-resolution computed tomography (HRCT), chest X-ray (CXR), and clinical manifestations (CM) to identify initial smear-negative (iSN) active pulmonary tuberculosis (aPTB) [iSN-aPTB] in patients with iSN-pulmonary diseases (PD) and acute lung injury (ALI). In the derivation cohort, the [iSN-PD] with ALI patients were divided into the [iSN-aPTB] (G1, n = 26) and [non-aPTB-PD] (G2, n = 233) groups. Lung morphology, number, and lobar (segmental) distribution were evaluated using CXR and HRCT. A multivariate analysis was performed to identify independent variables associated with G1, which were used to generate predictive score models for G1. The predictive model was validated in a separate population of patients (n = 372) with [iSN-PD] and (ALI). The validated model for [HRCT (CXR + Hypoalbuminemia)] had 93.5% (25.8%) sensitivity, 99.5% (89.4%) specificity, and a negative predictive value of 99.5% (93.0%). For [iSN-aPTB], the post-test probability in the derivation cohort (prevalence = 10%), validation cohort (prevalence = 8.3%), and the given prevalence (prevalence = 1%) was 88.7%, 94.4%, and 41.5%, respectively. The HRCT model effectively identified the [iSN-aPTB] subjects among the [iSN-PD] with ALI, regardless of CM. The [non-aPTB-PD] were also correctly classified by the HRCT and [CXR + Hypoalbuminemia] models.",2019 Mar 14,"Yeh, Jun-Jun",Sci Rep,,,False
4032ba4bcf75cb306c06c5f2e9ba6b8580781a8f,PMC,Predictors of Initial Smear-Negative Active Pulmonary Tuberculosis with Acute Early Stage Lung Injury by High-Resolution Computed Tomography and Clinical Manifestations: An Auxiliary Model in Critical Patients,http://dx.doi.org/10.1038/s41598-019-40799-w,PMC6418143,30872774,CC BY,"This study evaluated the diagnostic use of high-resolution computed tomography (HRCT), chest X-ray (CXR), and clinical manifestations (CM) to identify initial smear-negative (iSN) active pulmonary tuberculosis (aPTB) [iSN-aPTB] in patients with iSN-pulmonary diseases (PD) and acute lung injury (ALI). In the derivation cohort, the [iSN-PD] with ALI patients were divided into the [iSN-aPTB] (G1, n = 26) and [non-aPTB-PD] (G2, n = 233) groups. Lung morphology, number, and lobar (segmental) distribution were evaluated using CXR and HRCT. A multivariate analysis was performed to identify independent variables associated with G1, which were used to generate predictive score models for G1. The predictive model was validated in a separate population of patients (n = 372) with [iSN-PD] and (ALI). The validated model for [HRCT (CXR + Hypoalbuminemia)] had 93.5% (25.8%) sensitivity, 99.5% (89.4%) specificity, and a negative predictive value of 99.5% (93.0%). For [iSN-aPTB], the post-test probability in the derivation cohort (prevalence = 10%), validation cohort (prevalence = 8.3%), and the given prevalence (prevalence = 1%) was 88.7%, 94.4%, and 41.5%, respectively. The HRCT model effectively identified the [iSN-aPTB] subjects among the [iSN-PD] with ALI, regardless of CM. The [non-aPTB-PD] were also correctly classified by the HRCT and [CXR + Hypoalbuminemia] models.",2019 Mar 14,"Yeh, Jun-Jun",Sci Rep,,,True
d5d7598d6c651d21a0b4fd2153a98e3665f18ff5,PMC,An Effective Neutralizing Antibody Against Influenza Virus H1N1 from Human B Cells,http://dx.doi.org/10.1038/s41598-019-40937-4,PMC6418199,30872685,CC BY,"Influenza is a contagious acute respiratory disease caused by the influenza virus infection. Hemagglutinin (HA) is an important target in the therapeutic treatment and diagnostic detection of the influenza virus. Influenza A virus encompasses several different HA subtypes with different strains, which are constantly changing. In this study, we identified a fully human H1N1 neutralizing antibody (32D6) via an Epstein-Barr virus-immortalized B cell-based technology. 32D6 specifically neutralizes the clinically isolated H1N1 strains after the 2009 pandemic but not the earlier strains. The epitope was identified through X-ray crystallographic analysis of the 32D6-Fab/HA1 complex structure, which revealed a unique loop conformation located on the top surface of HA. The major region is composed of two peptide segments (residues 172–177 and 206–213), which form an abreast loop conformation. The residue T262 between the two loops forms a conformational epitope for recognition by 32D6. Three water molecules were observed at the interface of HA and the heavy chain, and they may constitute a stabilizing element for the 32D6-HA association. In addition, each 32D6-Fab is likely capable of blocking one HA trimer. This study provides important information on the strain specificity of 32D6 for the therapeutic treatment and detection of viral infection.",2019 Mar 14,"['Lee, Cheng-Chung', 'Yang, Chih-Ya', 'Lin, Li-Ling', 'Ko, Tzu-Ping', 'Chang, Alarng Hsun-Lang', 'Chang, Stanley Shi-Chung', 'Wang, Andrew H.-J.']",Sci Rep,,,False
cf533451f25297fe0d1a6006fc562568358cefb6,PMC,An Effective Neutralizing Antibody Against Influenza Virus H1N1 from Human B Cells,http://dx.doi.org/10.1038/s41598-019-40937-4,PMC6418199,30872685,CC BY,"Influenza is a contagious acute respiratory disease caused by the influenza virus infection. Hemagglutinin (HA) is an important target in the therapeutic treatment and diagnostic detection of the influenza virus. Influenza A virus encompasses several different HA subtypes with different strains, which are constantly changing. In this study, we identified a fully human H1N1 neutralizing antibody (32D6) via an Epstein-Barr virus-immortalized B cell-based technology. 32D6 specifically neutralizes the clinically isolated H1N1 strains after the 2009 pandemic but not the earlier strains. The epitope was identified through X-ray crystallographic analysis of the 32D6-Fab/HA1 complex structure, which revealed a unique loop conformation located on the top surface of HA. The major region is composed of two peptide segments (residues 172–177 and 206–213), which form an abreast loop conformation. The residue T262 between the two loops forms a conformational epitope for recognition by 32D6. Three water molecules were observed at the interface of HA and the heavy chain, and they may constitute a stabilizing element for the 32D6-HA association. In addition, each 32D6-Fab is likely capable of blocking one HA trimer. This study provides important information on the strain specificity of 32D6 for the therapeutic treatment and detection of viral infection.",2019 Mar 14,"['Lee, Cheng-Chung', 'Yang, Chih-Ya', 'Lin, Li-Ling', 'Ko, Tzu-Ping', 'Chang, Alarng Hsun-Lang', 'Chang, Stanley Shi-Chung', 'Wang, Andrew H.-J.']",Sci Rep,,,True
faca0e63f60b82dc6ce3f2ff08c39da677ba7ecc,PMC,"Detection and characterisation of canine astrovirus, canine parvovirus and canine papillomavirus in puppies using next generation sequencing",http://dx.doi.org/10.1038/s41598-019-41045-z,PMC6418273,30872719,CC BY,"Gastroenteritis in young animals is a clinical presentation with many infectious and non- infectious aetiologies. We used next generation sequencing (NGS) to investigate the possible infectious causes of gastroenteritis in puppies from a dog kennel in Victoria, Australia. The near complete genome of a canine astrovirus was obtained from pooled faecal samples, and was found to be 94.7% identical with a canine astrovirus detected in the United Kingdom in 2012. The phylogenetic analysis of the capsid gene found similarities to those of canine astroviruses identified in Italy in 2005 and in UK and Hungary in 2012, but distant from that of a canine astrovirus previously identified in Australia in 2012. Thus, different serotypes of canine astrovirus are likely circulating in Australia. The close relationship to European astroviruses also suggested that there had been recent movements of ancestor canine astroviruses between Australia and Europe. NGS also detected other infections in the puppies including several canine papillomaviruses and a canine parvovirus (vaccine strain) as well as a very low level of campylobacter. Canine astrovirus was the probable cause of diarrhoea in these puppies, with the possible involvement of campylobacter bacteria. NGS was effective as a non-targeted method to determine the likely infectious cause of gastroenteritis.",2019 Mar 14,"['Bhatta, Tarka Raj', 'Chamings, Anthony', 'Vibin, Jessy', 'Alexandersen, Soren']",Sci Rep,,,False
999baa06c2bdc67ba7e4707ddcf5b3b296f85985,PMC,"Detection and characterisation of canine astrovirus, canine parvovirus and canine papillomavirus in puppies using next generation sequencing",http://dx.doi.org/10.1038/s41598-019-41045-z,PMC6418273,30872719,CC BY,"Gastroenteritis in young animals is a clinical presentation with many infectious and non- infectious aetiologies. We used next generation sequencing (NGS) to investigate the possible infectious causes of gastroenteritis in puppies from a dog kennel in Victoria, Australia. The near complete genome of a canine astrovirus was obtained from pooled faecal samples, and was found to be 94.7% identical with a canine astrovirus detected in the United Kingdom in 2012. The phylogenetic analysis of the capsid gene found similarities to those of canine astroviruses identified in Italy in 2005 and in UK and Hungary in 2012, but distant from that of a canine astrovirus previously identified in Australia in 2012. Thus, different serotypes of canine astrovirus are likely circulating in Australia. The close relationship to European astroviruses also suggested that there had been recent movements of ancestor canine astroviruses between Australia and Europe. NGS also detected other infections in the puppies including several canine papillomaviruses and a canine parvovirus (vaccine strain) as well as a very low level of campylobacter. Canine astrovirus was the probable cause of diarrhoea in these puppies, with the possible involvement of campylobacter bacteria. NGS was effective as a non-targeted method to determine the likely infectious cause of gastroenteritis.",2019 Mar 14,"['Bhatta, Tarka Raj', 'Chamings, Anthony', 'Vibin, Jessy', 'Alexandersen, Soren']",Sci Rep,,,True
5caced13bcb8a42cca41369c5a71ae7df5381ca8,PMC,Mucosal immune responses induced by oral administration recombinant Bacillus subtilis expressing the COE antigen of PEDV in newborn piglets,http://dx.doi.org/10.1042/BSR20182028,PMC6418403,30808716,CC BY,"Porcine epidemic diarrhea (PED) is a highly contagious disease in newborn piglets and causes substantial economic losses in the world. PED virus (PEDV) spreads by fecal–oral contact and can be prevented by oral immunization. Therefore, it is necessary to develop an effective oral vaccine against PEDV infection. Currently, Bacillus subtilis as recombinant vaccine carrier has been used for antigen delivery and proved well in immune effect and safety. The present study evaluated the immunogenicity of recombinant Bacillus subtilis (B. subtilis-RC) in piglets via oral administration. After oral immunization in piglets, B. subtilis-RC significantly increased the local mucosal immune responses. Oral administration with B. subtilis-RC significantly improved the level of specific mucosal immunoglobulin A (IgA) antibodies against PEDV infection, through enlarging the area of Peyer’s patches (PPs) and increasing the number of ileum IgA(+) secreting (SIgA) cells. In the meantime, B. subtilis-RC remarkably increased the number of intraepithelial lymphocytes (IELs). We also observed that oral administration of B. subtilis-RC significantly increased CD3(+)T lymphocytes’ numbers and up-regulated the ratio of CD4(+)/CD8(+) T cells. Furthermore, high titers of specific serum immunoglobulin G (IgG) revealed satisfactory systemic immune response against PEDV infection. In summary, our study demonstrated that oral administration of B. subtilis-RC could trigger a high level of local and systemic immune responses and would be a promising candidate vaccine against PEDV infection in piglets.",2019 Mar 15,"['Wang, Jialu', 'Huang, Lulu', 'Mou, Chunxiao', 'Zhang, En', 'Wang, Yongheng', 'Cao, Yanan', 'Yang, Qian']",Biosci Rep,,,True
42ef2bf3057aeedc9a51d599553ee98527e2bfb4,PMC,"Preparation, Characterization and Application of Polysaccharide-Based Metallic Nanoparticles: A Review",http://dx.doi.org/10.3390/polym9120689,PMC6418682,30965987,CC BY,"Polysaccharides are natural biopolymers that have been recognized to be the most promising hosts for the synthesis of metallic nanoparticles (MNPs) because of their outstanding biocompatible and biodegradable properties. Polysaccharides are diverse in size and molecular chains, making them suitable for the reduction and stabilization of MNPs. Considerable research has been directed toward investigating polysaccharide-based metallic nanoparticles (PMNPs) through host–guest strategy. In this review, approaches of preparation, including top-down and bottom-up approaches, are presented and compared. Different characterization techniques such as scanning electron microscopy, transmission electron microscopy, dynamic light scattering, UV-visible spectroscopy, Fourier-transform infrared spectroscopy, X-ray diffraction and small-angle X-ray scattering are discussed in detail. Besides, the applications of PMNPs in the field of wound healing, targeted delivery, biosensing, catalysis and agents with antimicrobial, antiviral and anticancer capabilities are specifically highlighted. The controversial toxicological effects of PMNPs are also discussed. This review can provide significant insights into the utilization of polysaccharides as the hosts to synthesize MPNs and facilitate their further development in synthesis approaches, characterization techniques as well as potential applications.",2017 Dec 8,"['Wang, Cong', 'Gao, Xudong', 'Chen, Zhongqin', 'Chen, Yue', 'Chen, Haixia']",Polymers (Basel),,,True
aeac4c993813c60687acf54e7a35957830c7b727,PMC,"Progress on the Implementation of Environmental Surveillance in the African Region, 2011-2016",,PMC6420122,30882093,CC BY,"OBJECTIVE: This article summarises the progress made since the introduction of environmental surveillance in the African Region. METHOD: Country selection was based on the poor AFP performance indicators i.e. Non polio AFP rate and stool adequacy. It was recommended that any country not meeting the required indicators should consider environmental surveillance activity as an additional tool to support AFP surveillance. The sites selection considered proximity to the target population, the size of the population to be sampled and the sensitivity of the sampling site. RESULTS: One hundred and fifty three sites have been established in Africa since 2011. In 2011, Nigeria was first country to introduce environmental surveillance and currently with of 59 validated sites, followed by Kenya in 2013 validating and sampling 9 sites and Angola 4 active sites in 2014. In 2014, Cameroon introduced ES and 31 sites followed by Niger with 9 sites and Madagascar with 23 sites. Later in the same year, Chad introduced ES activity and 4 active sites were selected. In 2015 Senegal introduced 3 sites, Guinea and Burkina Faso introduced 4 sites each., and. In 2016, a total of 179 Sabins, 36 Sabin 2s, 196 non polio enteroviruses (NPEV) and 1 vaccine-derived polioviruses (VDPV) were reported in Nigeria. Cameroon and Chad isolated 14 and 4 Sabins and 72 and 40 NPEV respectively. In Madagascar a total of 39 Sabins, 11 Sabin 2s and 277 NPEV were isolated. In other countries a majority of NPEV were isolated (data not shown). CONCLUSION: This report describes the progress and expansion of environmental surveillance that contributed to the identification of polioviruses from the environment and the interruption of wild poliovirus transmission in the African Region.",2018 Aug 2,"['Gumede, Nicksy', 'Okeibunor, Joseph', 'Diop, Ousmane', 'Baba, Maryceline', 'Barnor, Jacob', 'Mbaye, Salla', 'Ticha, Johnson', 'Weldegebriel, Goitom', 'Asghar, Humayun', 'Mkanda, Pascal']",J Immunol Sci,,,True
85c6f63e581817cce1d68e6a5bb856fdbe390d17,PMC,The Screening Research of NF-κB Inhibitors from Moutan Cortex Based on Bioactivity-Integrated UPLC-Q/TOF-MS,http://dx.doi.org/10.1155/2019/6150357,PMC6420966,30941197,CC BY,"Inflammation is a common and important pathological process, and nuclear factor-κB (NF-κB) is a key mediator of it. Moutan Cortex (MC), the dried root cortex of Paeonia suffruticosa Andr., is widely used as a remedy for the treatment of inflammatory diseases in Asian region. However, there are few studies on the systematic identification of NF-κB inhibitors of MC. In this study, the effect of inhibiting NF-κB activation of MC was assessed at the cellular level using a tumor necrosis factor-α (TNF-α) induced inflammatory model. Subsequently, ultra-performance liquid chromatography-quadrupole/time of flight-mass spectrometry (UPLC-Q/TOF-MS) combined with biological activity assay was established to screen and identify potential anti-inflammatory ingredients in MC. The results revealed that MC significantly inhibited the activation of NF-κB. Seven potential NF-κB inhibitors were screened from MC, including oxypaeoniflorin, paeoniflorin, galloylpaeoniflorin, benzoyloxypaeoniflorin, mudanpioside C, gallic acid, and paeonol. Among them, the NF-κB inhibitor activity of galloylpaeoniflorin, benzoyloxypaeoniflorin, and mudanpioside C is first reported here. In conclusion, the anti-inflammatory activity of MC was associated with the seven components mentioned above. And the bioactivity-integrated UPLC-Q/TOF which contains both chemical and bioactive details is suitable for screening active ingredients from natural medicines.",2019 Mar 3,"['Lu, Yujie', 'Liu, Wenjuan', 'Zhang, Man', 'Deng, Yanfang', 'Jiang, Min', 'Bai, Gang']",Evid Based Complement Alternat Med,,,True
95d1135211f245b882e54f2842ab328b89066452,PMC,CRISPR-Cas9 Mediated RNase L Knockout Regulates Cellular Function of PK-15 Cells and Increases PRV Replication,http://dx.doi.org/10.1155/2019/7398208,PMC6421005,30941371,CC BY,"Ribonuclease L (RNase L) is an important antiviral endoribonuclease regulated by type I IFN. RNase L is activated by viral infection and dsRNA. Because the role of swine RNase L (sRNase L) is not fully understood, in this study, we generated a sRNase L knockout PK-15 (KO-PK) cell line through the CRISPR/Cas9 gene editing system to evaluate the function of sRNase L. After transfection with CRISPR-Cas9 followed by selection using puromycin, sRNase L knockout in PK-15 cells was further validated by agarose gel electrophoresis, DNA sequencing, and Western blotting. The sRNase L KO-PK cells failed to trigger RNA degradation and induced less apoptosis than the parental PK-15 cells after transfected with poly (I: C). Furthermore, the levels of ISGs mRNA in sRNase L KO-PK cells were higher than those in the parental PK-15 cells after treated with poly (I: C). Finally, both wild type and attenuated pseudorabies viruses (PRV) replicated more efficiently in sRNase L KO-PK cells than the parental PK-15 cells. Taken together, these findings suggest that sRNase L has multiple biological functions including cellular single-stranded RNA degradation, induction of apoptosis, downregulation of transcript levels of ISGs, and antiviral activity against PRV. The sRNase L KO-PK cell line will be a valuable tool for studying functions of sRNase L as well as for producing PRV attenuated vaccine.",2019 Mar 3,"['Sui, Chao', 'Jiang, Dandan', 'Wu, Xiangju', 'Cong, Xiaoyan', 'Li, Feng', 'Shang, Yingli', 'Wang, Jinqiu', 'Liu, Sidang', 'Shan, Hu', 'Qi, Jing', 'Du, Yijun']",Biomed Res Int,,,True
a014fffc3ab64385d716b0da1cd66fcd75969083,PMC,Multiscale Computational Models for Respiratory Aerosol Dynamics with Medical Applications,http://dx.doi.org/10.1155/2019/4304139,PMC6421775,30944577,CC BY,,2019 Mar 3,"['Feng, Yu', 'Chen, Xiaole', 'Yang, Mingshi', 'Dong, Ke-jun']",Comput Math Methods Med,,,False
849323d550c05b7686a3ce258800f42fbd5f46be,PMC,Cellular entry and uncoating of naked and quasi-enveloped human hepatoviruses,http://dx.doi.org/10.7554/eLife.43983,PMC6422491,30801249,CC BY,"Many ‘non-enveloped’ viruses, including hepatitis A virus (HAV), are released non-lytically from infected cells as infectious, quasi-enveloped virions cloaked in host membranes. Quasi-enveloped HAV (eHAV) mediates stealthy cell-to-cell spread within the liver, whereas stable naked virions shed in feces are optimized for environmental transmission. eHAV lacks virus-encoded surface proteins, and how it enters cells is unknown. We show both virion types enter by clathrin- and dynamin-dependent endocytosis, facilitated by integrin β(1), and traffic through early and late endosomes. Uncoating of naked virions occurs in late endosomes, whereas eHAV undergoes ALIX-dependent trafficking to lysosomes where the quasi-envelope is enzymatically degraded and uncoating ensues coincident with breaching of endolysosomal membranes. Neither virion requires PLA2G16, a phospholipase essential for entry of other picornaviruses. Thus naked and quasi-enveloped virions enter via similar endocytic pathways, but uncoat in different compartments and release their genomes to the cytosol in a manner mechanistically distinct from other Picornaviridae.",,"['Rivera-Serrano, Efraín E', 'González-López, Olga', 'Das, Anshuman', 'Lemon, Stanley M']",eLife.; 8:e43983,,,True
09502ec42f6aa93236fd3cf2ccc8f830f21555b6,PMC,Cellular entry and uncoating of naked and quasi-enveloped human hepatoviruses,http://dx.doi.org/10.7554/eLife.43983,PMC6422491,30801249,CC BY,"Many ‘non-enveloped’ viruses, including hepatitis A virus (HAV), are released non-lytically from infected cells as infectious, quasi-enveloped virions cloaked in host membranes. Quasi-enveloped HAV (eHAV) mediates stealthy cell-to-cell spread within the liver, whereas stable naked virions shed in feces are optimized for environmental transmission. eHAV lacks virus-encoded surface proteins, and how it enters cells is unknown. We show both virion types enter by clathrin- and dynamin-dependent endocytosis, facilitated by integrin β(1), and traffic through early and late endosomes. Uncoating of naked virions occurs in late endosomes, whereas eHAV undergoes ALIX-dependent trafficking to lysosomes where the quasi-envelope is enzymatically degraded and uncoating ensues coincident with breaching of endolysosomal membranes. Neither virion requires PLA2G16, a phospholipase essential for entry of other picornaviruses. Thus naked and quasi-enveloped virions enter via similar endocytic pathways, but uncoat in different compartments and release their genomes to the cytosol in a manner mechanistically distinct from other Picornaviridae.",,"['Rivera-Serrano, Efraín E', 'González-López, Olga', 'Das, Anshuman', 'Lemon, Stanley M']",eLife.; 8:e43983,,,False
246a98b042ab326afd859e0e14579431f078894b,PMC,Genetic Improvement in Dromedary Camels: Challenges and Opportunities,http://dx.doi.org/10.3389/fgene.2019.00167,PMC6422876,30915101,CC BY,,2019 Mar 12,"['Abri, Mohammed A. Al', 'Faye, Bernard']",Front Genet,,,True
4d44adb48335ef12290b3584771b424aa28185e5,PMC,Yersinia pestis Interacts With SIGNR1 (CD209b) for Promoting Host Dissemination and Infection,http://dx.doi.org/10.3389/fimmu.2019.00096,PMC6422942,30915064,CC BY,"Yersinia pestis, a Gram-negative bacterium and the etiologic agent of plague, has evolved from Yersinia pseudotuberculosis, a cause of a mild enteric disease. However, the molecular and biological mechanisms of how Y. pseudotuberculosis evolved to such a remarkably virulent pathogen, Y. pestis, are not clear. The ability to initiate a rapid bacterial dissemination is a characteristic hallmark of Y. pestis infection. A distinguishing characteristic between the two Yersinia species is that Y. pseudotuberculosis strains possess an O-antigen of lipopolysaccharide (LPS) while Y. pestis has lost the O-antigen during evolution and therefore exposes its core LPS. In this study, we showed that Y. pestis utilizes its core LPS to interact with SIGNR1 (CD209b), a C-type lectin receptor on antigen presenting cells (APCs), leading to bacterial dissemination to lymph nodes, spleen and liver, and the initiation of a systemic infection. We therefore propose that the loss of O-antigen represents a critical step in the evolution of Y. pseudotuberculosis into Y. pestis in terms of hijacking APCs, promoting bacterial dissemination and causing the plague.",2019 Mar 12,"['Yang, Kun', 'He, Yingxia', 'Park, Chae Gyu', 'Kang, Young Sun', 'Zhang, Pei', 'Han, Yanping', 'Cui, Yujun', 'Bulgheresi, Silvia', 'Anisimov, Andrey P.', 'Dentovskaya, Svetlana V.', 'Ying, Xiaoling', 'Jiang, Lingyu', 'Ding, Honghui', 'Njiri, Olivia Adhiambo', 'Zhang, Shusheng', 'Zheng, Guoxing', 'Xia, Lianxu', 'Kan, Biao', 'Wang, Xin', 'Jing, Huaiqi', 'Yan, Meiying', 'Li, Wei', 'Wang, Yuanzhi', 'Xiamu, Xiding', 'Chen, Gang', 'Ma, Ding', 'Bartra, Sara Schesser', 'Plano, Gregory V.', 'Klena, John D.', 'Yang, Ruifu', 'Skurnik, Mikael', 'Chen, Tie']",Front Immunol,,,True
5d2bf5e0b24d87dd18a0dba2ef76131efc31fb2c,PMC,Digital epidemiology and global health security; an interdisciplinary conversation,http://dx.doi.org/10.1186/s40504-019-0091-8,PMC6423775,30887141,CC BY,"Contemporary infectious disease surveillance systems aim to employ the speed and scope of big data in an attempt to provide global health security. Both shifts - the perception of health problems through the framework of global health security and the corresponding technological approaches – imply epistemological changes, methodological ambivalences as well as manifold societal effects. Bringing current findings from social sciences and public health praxis into a dialogue, this conversation style contribution points out several broader implications of changing disease surveillance. The conversation covers epidemiological issues such as the shift from expert knowledge to algorithmic knowledge, the securitization of global health, and the construction of new kinds of threats. Those developments are detailed and discussed in their impacts for health provision in a broader sense.",2019 Mar 19,"['Eckmanns, Tim', 'Füller, Henning', 'Roberts, Stephen L.']",Life Sci Soc Policy,,,True
3380d0cb8447aa4741878f8a3d300a3765ed9a40,PMC,Hemorrhagic Fever-Causing Arenaviruses: Lethal Pathogens and Potent Immune Suppressors,http://dx.doi.org/10.3389/fimmu.2019.00372,PMC6424867,30918506,CC BY,"Hemorrhagic fevers (HF) resulting from pathogenic arenaviral infections have traditionally been neglected as tropical diseases primarily affecting African and South American regions. There are currently no FDA-approved vaccines for arenaviruses, and treatments have been limited to supportive therapy and use of non-specific nucleoside analogs, such as Ribavirin. Outbreaks of arenaviral infections have been limited to certain geographic areas that are endemic but known cases of exportation of arenaviruses from endemic regions and socioeconomic challenges for local control of rodent reservoirs raise serious concerns about the potential for larger outbreaks in the future. This review synthesizes current knowledge about arenaviral evolution, ecology, transmission patterns, life cycle, modulation of host immunity, disease pathogenesis, as well as discusses recent development of preventative and therapeutic pursuits against this group of deadly viral pathogens.",2019 Mar 13,"['Brisse, Morgan E.', 'Ly, Hinh']",Front Immunol,,,True
c07b96b0ac94d1403d44dff3bc6ad12a64d171c1,PMC,Alternative Methods of Vaccine Delivery: An Overview of Edible and Intradermal Vaccines,http://dx.doi.org/10.1155/2019/8303648,PMC6425294,30949518,CC BY,"Vaccines are recognized worldwide as one of the most important tools for combating infectious diseases. Despite the tremendous value conferred by currently available vaccines toward public health, the implementation of additional vaccine platforms is also of key importance. In fact, currently available vaccines possess shortcomings, such as inefficient triggering of a cell-mediated immune response and the lack of protective mucosal immunity. In this regard, recent work has been focused on vaccine delivery systems, as an alternative to injectable vaccines, to increase antigen stability and improve overall immunogenicity. In particular, novel strategies based on edible or intradermal vaccine formulations have been demonstrated to trigger both a systemic and mucosal immune response. These novel vaccination delivery systems offer several advantages over the injectable preparations including self-administration, reduced cost, stability, and elimination of a cold chain. In this review, the latest findings and accomplishments regarding edible and intradermal vaccines are described in the context of the system used for immunogen expression, their molecular features and capacity to induce a protective systemic and mucosal response.",2019 Mar 4,"['Criscuolo, E.', 'Caputo, V.', 'Diotti, R. A.', 'Sautto, G. A.', 'Kirchenbaum, G. A.', 'Clementi, N.']",J Immunol Res,,,True
9a24a0a85d33c5665889c6de594c961478260c0c,PMC,Quantifying heterogeneous contact patterns in Japan: a social contact survey,http://dx.doi.org/10.1186/s12976-019-0102-8,PMC6425701,30890153,CC BY,"BACKGROUND: Social contact surveys can greatly help in quantifying the heterogeneous patterns of infectious disease transmission. The present study aimed to conduct a contact survey in Japan, offering estimates of contact by age and location and validating a social contact matrix using a seroepidemiological dataset of influenza. METHODS: An internet-based questionnaire survey was conducted, covering all 47 prefectures in Japan and including a total of 1476 households. The social contact matrix was quantified assuming reciprocity and using the maximum likelihood method. By imposing several parametric assumptions for the next-generation matrix, the empirical seroepidemiological data of influenza A (H1N1) 2009 was analysed and we estimated the basic reproduction number, R(0). RESULTS: In total, the reported number of contacts on weekdays was 10,682 whereas that on weekend days was 8867. Strong age-dependent assortativity was identified. Forty percent of weekday contacts took place at schools or workplaces, but that declined to 14% on weekends. Accounting for the age-dependent heterogeneity with the known social contact matrix, the minimum value of the Akaike information criterion was obtained and R(0) was estimated at 1.45 (95% confidence interval: 1.42, 1.49). CONCLUSIONS: Survey datasets will be useful for parameterizing the heterogeneous transmission model of various directly transmitted infectious diseases in Japan. Age-dependent assortativity, especially among children, along with numerous contacts in school settings on weekdays implies the potential effectiveness of school closure. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12976-019-0102-8) contains supplementary material, which is available to authorized users.",2019 Mar 20,"['Munasinghe, Lankeshwara', 'Asai, Yusuke', 'Nishiura, Hiroshi']",Theor Biol Med Model,,,True
8936f7734e68b14b079a2645b8df710c8958e943,PMC,The perceived effectiveness of MERS-CoV educational programs and knowledge transfer among primary healthcare workers: a cross-sectional survey,http://dx.doi.org/10.1186/s12879-019-3898-2,PMC6427879,30898086,CC BY,"BACKGROUND: Knowledge transfer of Middle East respiratory syndrome coronavirus (MERS-CoV) involves the dissemination of created/acquired information on MERS-CoV in hospitals, making this information accessible to all healthcare workers (HCWs). This study evaluated the perceived effectiveness of MERS-CoV educational programs and knowledge transfer among primary care HCWs at a hospital in Saudi Arabia that witnessed the largest outbreak of confirmed MERS-CoV cases in this country. METHODS: A survey was distributed among primary care HCWs at five clinics in Saudi Arabia in 2016. Those with non-direct patient care responsibilities were excluded. Their knowledge was evaluated against facts published by Mayo Clinic Foundation, and its percentage mean score (PMS) ± standard deviation was calculated. HCWs’ perceived effectiveness of educational programs and knowledge transfer was classified as negative or positive. RESULTS: Sample comprised of 404 HCWs, of which 64% were females and 36% were males. Almost 26% were ≤ 30 years old, and 42% had > 10 years of work experience. Almost 46.5% were nurses, 23.0% physicians, 18.1% were pharmacists, and 12.4% were technical staff. PMS for knowledge was 71.1 ± 19.4. The prevalence of negative perceptions towards educational programs was 22.5% and of knowledge transfer was 20.8%. Older(> 40 years of age) and more experienced(> 10 years) HCWs had the highest PMS for knowledge(73.4 ± 18.9,P = 0.005 and 76.9 ± 15.7,P < 0.001 respectively). Negative perceptions of educational programs (49.4 ± 20.7; P < 0.001) and knowledge transfer (46.0 ± 19.7; P = 0.001) were associated with a lower knowledge PMS. Males were 2.4[95% confidence interval 1.4–4.2] times and 2.0[1.1–3.5] times more likely to have negative perceptions of educational programs and knowledge transfer (adjusted (adj.)P = 0.001 and adj. P = 0.023, respectively). Physicians/pharmacists were 1.8[1.03–3.11] and 2.8[1.6–5.0] times more likely to have negative perceptions of both outcomes (adj. P = 0.038 and adj. P = 0.001, respectively). Less experienced HCWs were 2.1[1.3–3.5] times and 4.9[2.6–9.2] times more likely to exhibit negative perceptions of the two outcomes (adj. P < 0.001 each). CONCLUSIONS: A negative perception of the effectiveness of MERS-CoV knowledge transfer was associated with poorer knowledge and was more prevalent among male HCWs, physicians/pharmacists and less experienced HCWs. Hospitals should always refer to efficient knowledge sharing and educational strategies that render beneficial outcomes to patients, HCWs, and the public community. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-3898-2) contains supplementary material, which is available to authorized users.",2019 Mar 21,"['Aldohyan, Meshal', 'Al-Rawashdeh, Nedal', 'Sakr, Farouk M.', 'Rahman, Saeed', 'Alfarhan, Ali I.', 'Salam, Mahmoud']",BMC Infect Dis,,,True
ed919dda9ed5eb8ab60b40ad6eb04bf2d68cc63f,PMC,Studies on B Cells in the Fruit-Eating Black Flying Fox (Pteropus alecto),http://dx.doi.org/10.3389/fimmu.2019.00489,PMC6428034,30930908,CC BY,"The ability of bats to act as reservoir for viruses that are highly pathogenic to humans suggests unique properties and functional characteristics of their immune system. However, the lack of bat specific reagents, in particular antibodies, has limited our knowledge of bat's immunity. Here, we report a panel of cross-reactive antibodies against MHC-II, NK1.1, CD3, CD21, CD27, and immunoglobulin (Ig), that allows flow cytometry analysis of B, T and NK cell populations in two different fruit-eating bat species namely, Pteropus alecto and E. spelaea. Results confirmed predominance of T cells in the spleen and blood of bats, as previously reported by us. However, the percentages of B cells in bone marrow and NK cells in spleen varied greatly between wild caught P. alecto bats and E. spelaea colony bats, which may reflect inherent differences of their immune system or different immune status. Other features of bat B cells were investigated. A significant increase in sIg(+) B cell population was observed in the spleen and blood from LPS-injected bats but not from poly I:C-injected bats, supporting T-independent polyclonal B cell activation by LPS. Furthermore, using an in vitro calcium release assay, P. alecto B cells exhibited significant calcium release upon cross-linking of their B cell receptor. Together, this work contributes to improve our knowledge of bat adaptive immunity in particular B cells.",2019 Mar 14,"['Periasamy, Pravin', 'Hutchinson, Paul E.', 'Chen, Jinmiao', 'Bonne, Isabelle', 'Shahul Hameed, Shahana Shereene', 'Selvam, Pavithra', 'Hey, Ying Ying', 'Fink, Katja', 'Irving, Aaron T.', 'Dutertre, Charles-Antoine', 'Baker, Michelle', 'Crameri, Gary', 'Wang, Lin-Fa', 'Alonso, Sylvie']",Front Immunol,,,True
10f4664e4d1e58018892a7a2ab1eae868d59f2f3,PMC,Optimal media reporting intensity on mitigating spread of an emerging infectious disease,http://dx.doi.org/10.1371/journal.pone.0213898,PMC6428274,30897141,CC BY,"Mass media reports can induce individual behaviour change during a disease outbreak, which has been found to be useful as it reduces the force of infection. We propose a compartmental model by including a new compartment of the intensity of the media reports, which extends existing models by considering a novel media function, which is dependent both on the number of infected individuals and on the intensity of mass media. The existence and stability of the equilibria are analyzed and an optimal control problem of minimizing the total number of cases and total cost is considered, using reduction or enhancement in the media reporting rate as the control. With the help of Pontryagin’s Maximum Principle, we obtain the optimal media reporting intensity. Through parameterization of the model with the 2009 A/H1N1 influenza outbreak data in the 8th Hospital of Xi’an in Shaanxi Province of China, we obtain the basic reproduction number for the formulated model with two particular media functions. The optimal media reporting intensity obtained here indicates that during the early stage of an epidemic we should quickly enhance media reporting intensity, and keep it at a maximum level until it can finally weaken when epidemic cases have decreased significantly. Numerical simulations show that media impact reduces the number of cases during an epidemic, but that the number of cases is further mitigated under the optimal reporting intensity. Sensitivity analysis implies that the outbreak severity is more sensitive to the weight α(1) (weight of media effect sensitive to infected individuals) than weight α(2) (weight of media effect sensitive to media items).",2019 Mar 21,"['Zhou, Weike', 'Xiao, Yanni', 'Heffernan, Jane Marie']",PLoS One,,,True
00922f3da17d32e4e0de87d56cddd61776355ce4,PMC,Optimal media reporting intensity on mitigating spread of an emerging infectious disease,http://dx.doi.org/10.1371/journal.pone.0213898,PMC6428274,30897141,CC BY,"Mass media reports can induce individual behaviour change during a disease outbreak, which has been found to be useful as it reduces the force of infection. We propose a compartmental model by including a new compartment of the intensity of the media reports, which extends existing models by considering a novel media function, which is dependent both on the number of infected individuals and on the intensity of mass media. The existence and stability of the equilibria are analyzed and an optimal control problem of minimizing the total number of cases and total cost is considered, using reduction or enhancement in the media reporting rate as the control. With the help of Pontryagin’s Maximum Principle, we obtain the optimal media reporting intensity. Through parameterization of the model with the 2009 A/H1N1 influenza outbreak data in the 8th Hospital of Xi’an in Shaanxi Province of China, we obtain the basic reproduction number for the formulated model with two particular media functions. The optimal media reporting intensity obtained here indicates that during the early stage of an epidemic we should quickly enhance media reporting intensity, and keep it at a maximum level until it can finally weaken when epidemic cases have decreased significantly. Numerical simulations show that media impact reduces the number of cases during an epidemic, but that the number of cases is further mitigated under the optimal reporting intensity. Sensitivity analysis implies that the outbreak severity is more sensitive to the weight α(1) (weight of media effect sensitive to infected individuals) than weight α(2) (weight of media effect sensitive to media items).",2019 Mar 21,"['Zhou, Weike', 'Xiao, Yanni', 'Heffernan, Jane Marie']",PLoS One,,,False
e283c964691d950836fd62790ff4c032b8b1a56a,PMC,"Evaluation of the Inhibitory Effects of (E)-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(naphthalen-1-yl)prop-2-en-1-one (DiNap), a Natural Product Analog, on the Replication of Type 2 PRRSV In Vitro and In Vivo",http://dx.doi.org/10.3390/molecules24050887,PMC6429065,30832429,CC BY,"DiNap [(E)-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(naphthalen-1-yl)prop-2-en-1-one], an analog of a natural product (the chalcone flavokawain), was synthesized and characterized in this study. Porcine reproductive and respiratory syndrome virus (PRRSV) is the most challenging threat to the swine industry worldwide. Currently, commercially available vaccines are ineffective for controlling porcine reproductive and respiratory syndrome (PRRS) in pigs. Therefore, a pharmacological intervention may represent an alternative control measure for PRRSV infection. Hence, the present study evaluated the effects of DiNap on the replication of VR2332 (a prototype strain of type 2 PRRSV). Initially, in vitro antiviral assays against VR2332 were performed in MARC-145 cells and porcine alveolar macrophages (PAMs). Following this, a pilot study was conducted in a pig model to demonstrate the effects of DiNap following VR2332 infection. DiNap inhibited VR2332 replication in both cell lines in a dose-dependent manner, and viral growth was completely suppressed at concentrations ≥0.06 mM, without significant cytotoxicity. Consistent with these findings, in the pig study, DiNap also reduced viral loads in the serum and lungs and enhanced the weight gain of pigs following VR2332 infection, as indicated by comparison of the DiNap-treated groups to the untreated control (NC) group. In addition, DiNap-treated pigs had fewer gross and microscopic lesions in their lungs than NC pigs. Notably, virus transmission was also delayed by approximately 1 week in uninfected contact pigs within the same group after treatment with DiNap. Taken together, these results suggest that DiNap has potential anti-PRRSV activity and could be useful as a prophylactic or post-exposure treatment drug to control PRRSV infection in pigs.",2019 Mar 3,"['Khatun, Amina', 'Park, Sun You', 'Shabir, Nadeem', 'Nazki, Salik', 'Kang, A-Rum', 'Jeong, Chang-Gi', 'Seo, Byoung-Joo', 'Yang, Myeon-Sik', 'Kim, Bumseok', 'Seo, Young Ho', 'Kim, Won-Il']",Molecules,,,True
76de3c0c853bd138ae36cf9128ee2fb0943764fc,PMC,"Design and Synthesis of Novel Anti-Proliferative Emodin Derivatives and Studies on their Cell Cycle Arrest, Apoptosis Pathway and Migration",http://dx.doi.org/10.3390/molecules24050884,PMC6429262,30832378,CC BY,"Emodin is a cell arrest and apoptosis-inducing compound that is widely distributed in different plants (rhubarb, aloe), lichens and terrestrial fungi, and also isolated from marine-derived fungi and marine sponge-associated fungi. In this study, we designed and synthesized a novel series of emodin derivatives by binding emodin to an amino acid using linkers of varying lengths and composition, and evaluated their anti-proliferative activities using HepG2 cells (human hepatic carcinoma), MCF-7 cells (human breast cancer) and human normal liver L02 cells. Most of these derivatives showed moderate to potent anti-proliferative activities. Notably, compound 7a exhibited potent anti-proliferative activity against HepG2 cells with the half maximal inhibitory concentration (IC(50)) value of 4.95 µM, which was enhanced 8.8-fold compared to the parent compound emodin (IC(50) = 43.87 µM), and it also exhibited better selective anti-proliferative activity and specificity than emodin. Moreover, further experiments demonstrated that compound 7a displayed a significant efficacy of inducing apoptosis through mitochondrial pathway via release of cytochrome c from mitochondria and subsequent activation of caspase-9 and caspase-3, inducing cell arrest at G0/G1 phase, as well as suppression of cell migration of tumor cells. The preliminary results suggested that compound 7a could be a promising lead compound for the discovery of novel anti-tumor drugs and has the potential for further investigations as an anti-cancer drug.",2019 Mar 2,"['Yang, Kun', 'Jin, Ming-Ji', 'Quan, Zhe-Shan', 'Piao, Hu-Ri']",Molecules,,,True
985ac2b043a600d68f67a1341a5f541598c5abae,PMC,"Design and Synthesis of Novel Anti-Proliferative Emodin Derivatives and Studies on their Cell Cycle Arrest, Apoptosis Pathway and Migration",http://dx.doi.org/10.3390/molecules24050884,PMC6429262,30832378,CC BY,"Emodin is a cell arrest and apoptosis-inducing compound that is widely distributed in different plants (rhubarb, aloe), lichens and terrestrial fungi, and also isolated from marine-derived fungi and marine sponge-associated fungi. In this study, we designed and synthesized a novel series of emodin derivatives by binding emodin to an amino acid using linkers of varying lengths and composition, and evaluated their anti-proliferative activities using HepG2 cells (human hepatic carcinoma), MCF-7 cells (human breast cancer) and human normal liver L02 cells. Most of these derivatives showed moderate to potent anti-proliferative activities. Notably, compound 7a exhibited potent anti-proliferative activity against HepG2 cells with the half maximal inhibitory concentration (IC(50)) value of 4.95 µM, which was enhanced 8.8-fold compared to the parent compound emodin (IC(50) = 43.87 µM), and it also exhibited better selective anti-proliferative activity and specificity than emodin. Moreover, further experiments demonstrated that compound 7a displayed a significant efficacy of inducing apoptosis through mitochondrial pathway via release of cytochrome c from mitochondria and subsequent activation of caspase-9 and caspase-3, inducing cell arrest at G0/G1 phase, as well as suppression of cell migration of tumor cells. The preliminary results suggested that compound 7a could be a promising lead compound for the discovery of novel anti-tumor drugs and has the potential for further investigations as an anti-cancer drug.",2019 Mar 2,"['Yang, Kun', 'Jin, Ming-Ji', 'Quan, Zhe-Shan', 'Piao, Hu-Ri']",Molecules,,,False
80e940d11337db34b2dc48dc4002c5d79aff96d4,PMC,Recent Advances in Aptamer Discovery and Applications,http://dx.doi.org/10.3390/molecules24050941,PMC6429292,30866536,CC BY,"Aptamers are short, single-stranded DNA, RNA, or synthetic XNA molecules that can be developed with high affinity and specificity to interact with any desired targets. They have been widely used in facilitating discoveries in basic research, ensuring food safety and monitoring the environment. Furthermore, aptamers play promising roles as clinical diagnostics and therapeutic agents. This review provides update on the recent advances in this rapidly progressing field of research with particular emphasis on generation of aptamers and their applications in biosensing, biotechnology and medicine. The limitations and future directions of aptamers in target specific delivery and real-time detection are also discussed.",2019 Mar 7,"['Zhang, Yang', 'Lai, Bo Shiun', 'Juhas, Mario']",Molecules,,,True
4dd0f09aa22d567e9f5f9a0bebd8686be35da853,PMC,Advances in Zika Virus–Host Cell Interaction: Current Knowledge and Future Perspectives,http://dx.doi.org/10.3390/ijms20051101,PMC6429326,30836648,CC BY,"Emerging mosquito-transmitted RNA viruses, such as Zika virus (ZIKV) and Chikungunya represent human pathogens of an immense global health problem. In particular, ZIKV has emerged explosively since 2007 to cause a series of epidemics in the South Pacific and most recently in the Americas. Although typical ZIKV infections are asymptomatic, ZIKV infection during pregnancy is increasingly associated with microcephaly and other fetal developmental abnormalities. In the last few years, genomic and molecular investigations have established a remarkable progress on the pathogenic mechanisms of ZIKV infection using in vitro and in vivo models. Here, we highlight recent advances in ZIKV-host cell interaction studies, including cellular targets of ZIKV, ZIKV-mediated cell death mechanisms, host cell restriction factors that limit ZIKV replication, and immune evasion mechanisms utilized by ZIKV. Understanding of the mechanisms of ZIKV–host interaction at the cellular level will contribute crucial insights into the development of ZIKV therapeutics and vaccines.",2019 Mar 4,"['Lee, Jae Kyung', 'Shin, Ok Sarah']",Int J Mol Sci,,,True
de9f765a9c35d3ea9c4423235277d69e6bab1823,PMC,Potent antiviral activity of carbohydrate-specific algal and leguminous lectins from the Brazilian biodiversity,http://dx.doi.org/10.1039/c8md00508g,PMC6430086,30996857,CC BY,"Brazil has one of the largest biodiversities in the world. The search for new natural products extracted from the Brazilian flora may lead to the discovery of novel drugs with potential to treat infectious and other diseases. Here, we have investigated 9 lectins extracted and purified from the Northeastern Brazilian flora, from both leguminous species: Canavalia brasiliensis (ConBr), C. maritima (ConM), Dioclea lasiocarpa (DLasiL) and D. sclerocarpa (DSclerL), and algae Amansia multifida (AML), Bryothamniom seaforthii (BSL), Hypnea musciformis (HML), Meristiella echinocarpa (MEL) and Solieria filiformis (SfL). They were exposed to a panel of 18 different viruses, including HIV and influenza viruses. Several lectins showed highly potent antiviral activity, often within the low nanomolar range. DSclerL and DLasiL exhibited EC(50) values (effective concentration of lectin required to inhibit virus-induced cytopathicity by 50%) of 9 nM to 46 nM for HIV-1 and respiratory syncytial virus (RSV), respectively, DLasiL also inhibited feline corona virus at an EC(50) of 5 nM, and DSclerL, ConBr and ConM showed remarkably low EC(50) values ranging from 0.4 to 6 nM against influenza A virus strain H3N2 and influenza B virus. For HIV, evidence pointed to the blockage of entry of the virus into its target cells as the underlying mechanism of antiviral action of these lectins. Overall, the most promising lectins based on their EC(50) values were DLasiL, DSclerL, ConBr, ConM, SfL and HML. These novel findings indicate that lectins from the Brazilian flora may provide novel antiviral compounds with therapeutic potential.",2019 Jan 14,"['Gondim, Ana C. S.', 'Roberta da Silva, Suzete', 'Mathys, Leen', 'Noppen, Sam', 'Liekens, Sandra', 'Holanda Sampaio, Alexandre', 'Nagano, Celso S.', 'Renata Costa Rocha, Cintia', 'Nascimento, Kyria S.', 'Cavada, Benildo S.', 'Sadler, Peter J.', 'Balzarini, Jan']",Medchemcomm,,,True
a3ee4c7c3f02fd1d582f46a2e8965b2ea5da5ea8,PMC,Potent antiviral activity of carbohydrate-specific algal and leguminous lectins from the Brazilian biodiversity,http://dx.doi.org/10.1039/c8md00508g,PMC6430086,30996857,CC BY,"Brazil has one of the largest biodiversities in the world. The search for new natural products extracted from the Brazilian flora may lead to the discovery of novel drugs with potential to treat infectious and other diseases. Here, we have investigated 9 lectins extracted and purified from the Northeastern Brazilian flora, from both leguminous species: Canavalia brasiliensis (ConBr), C. maritima (ConM), Dioclea lasiocarpa (DLasiL) and D. sclerocarpa (DSclerL), and algae Amansia multifida (AML), Bryothamniom seaforthii (BSL), Hypnea musciformis (HML), Meristiella echinocarpa (MEL) and Solieria filiformis (SfL). They were exposed to a panel of 18 different viruses, including HIV and influenza viruses. Several lectins showed highly potent antiviral activity, often within the low nanomolar range. DSclerL and DLasiL exhibited EC(50) values (effective concentration of lectin required to inhibit virus-induced cytopathicity by 50%) of 9 nM to 46 nM for HIV-1 and respiratory syncytial virus (RSV), respectively, DLasiL also inhibited feline corona virus at an EC(50) of 5 nM, and DSclerL, ConBr and ConM showed remarkably low EC(50) values ranging from 0.4 to 6 nM against influenza A virus strain H3N2 and influenza B virus. For HIV, evidence pointed to the blockage of entry of the virus into its target cells as the underlying mechanism of antiviral action of these lectins. Overall, the most promising lectins based on their EC(50) values were DLasiL, DSclerL, ConBr, ConM, SfL and HML. These novel findings indicate that lectins from the Brazilian flora may provide novel antiviral compounds with therapeutic potential.",2019 Jan 14,"['Gondim, Ana C. S.', 'Roberta da Silva, Suzete', 'Mathys, Leen', 'Noppen, Sam', 'Liekens, Sandra', 'Holanda Sampaio, Alexandre', 'Nagano, Celso S.', 'Renata Costa Rocha, Cintia', 'Nascimento, Kyria S.', 'Cavada, Benildo S.', 'Sadler, Peter J.', 'Balzarini, Jan']",Medchemcomm,,,False
2af9fe633f4839d908785d15bac5c5233a53aca0,PMC,Sequelae of Acute Respiratory Distress Syndrome: Interest of Rehabilitation,http://dx.doi.org/10.1155/2019/7953141,PMC6431389,30963009,CC BY,"CASE PRESENTATION: This clinical case presents the history of a woman hospitalized for acute respiratory distress syndrome (ARDS). A 62-year-old woman, with regular physical activity and no history of respiratory disease or smoking, was hospitalized for moderate ARDS with bilateral pneumonitis. Fourteen days later, she was discharged from the intensive care unit and received respiratory physical therapy. One month later, she experienced exertional dyspnea. A regression of alveolar condensation with persistent sequelae at the pulmonary bases was noted. Three months later, the patient continued daily physical activity with satisfactory tolerance. A reduction in alveolar-capillary transfer, inappropriate hyperventilation upon exercise, and impairment of gas exchanges at maximal effort, suggestive of pulmonary shunt, were demonstrated. At the 6-month evaluation, the patient displayed exertional dyspnea with residual bilateral basal consolidations. Six months later, the dyspnea had ceased. The persistence of bilateral basal interstitial syndrome associated with bronchial dilatation and pleural-based consolidations was noted, as well as a stable impaired alveolar-capillary diffusing capacity. DISCUSSION: Upon discharge from intensive care, pulmonary follow-up should be proposed to ARDS survivors. Moreover, pulmonary function testing at rest and exercise is advised as soon as possible to evaluate the respiratory sequelae. This will help to limit the severity of complications through adapted exercise rehabilitation and then regular physical activity.",2019 Mar 6,"['Godeau, Elise', 'Debeaumont, David', 'Artaud-Macari, Elise', 'Lagache, Laurie', 'Bouar, Gurvan Le', 'Coquart, Jérémy']",Case Rep Crit Care,,,True
635ceee37108f92116fe91230b8d14b7ec5373be,PMC,An RT-PCR panel for rapid serotyping of dengue virus serotypes 1 to 4 in human serum and mosquito on a field-deployable PCR system,http://dx.doi.org/10.1371/journal.pone.0214328,PMC6433249,30908535,CC BY,"BACKGROUND: Dengue fever, a mosquito-borne disease, is caused by dengue virus (DENV) which includes four major serotypes (DENV-1, -2, -3, and -4). Some serotypes cause more severe diseases than the other; severe dengue is associated with secondary infections by a different serotype. Timely serotyping can provide early warning of dengue epidemics to improve management of patients and outbreaks. A mobile insulated isothermal PCR (iiPCR) system is available to allow molecular detection of pathogens near points of need. METHODOLOGY/PRINCIPLE FINDINGS: In this study, side-by-side comparison with the CDC DENV-1-4 Real Time RT-PCR (qRT-PCR) was performed to evaluate the performance of four singleplex DENV-1–4 serotyping reverse transcription-iiPCR (RT-iiPCR) reagents for DENV subtyping on the mobile PCR system. The four RT-iiPCRs did not react with Zika virus and chikungunya virus; tests with serial dilutions of the four DENV serotypes made in human serum showed they had detection endpoints comparable to those of the reference method, indicating great analytical sensitivity and specificity. Clinical performance of the RT-iiPCR reagents was evaluated by testing 40 serum samples each (around 20 target serotype-positive and 20 DENV-negative); all four reagents had high agreement (97.5–100%) with the reference qRT-PCR. Moreover, testing of mosquitoes separately infected experimentally with each serotype showed that the four reagents detected specifically their target DENV serotypes in mosquito. CONCLUSIONS/SIGNIFICANCE: With analytical and clinical performance comparable to the reference qRT-PCR assay, the four index RT-iiPCR reagents on the field-deployable PCR system can serve as a useful tool for DENV detection near points of needs.",2019 Mar 25,"['Tsai, Jih-Jin', 'Liu, Wei-Liang', 'Lin, Ping-Chang', 'Huang, Bo-Yi', 'Tsai, Ching-Yi', 'Chou, Pin-Hsing', 'Lee, Fu-Chun', 'Ping, Chia-Fong', 'Lee, Pei-Yu Alison', 'Liu, Li-Teh', 'Chen, Chun-Hong']",PLoS One,,,True
f3b9fc0f8e0a431366196d3e835e1ec368b379d1,PMC,Viruses and Evolution – Viruses First? A Personal Perspective,http://dx.doi.org/10.3389/fmicb.2019.00523,PMC6433886,30941110,CC BY,"The discovery of exoplanets within putative habitable zones revolutionized astrobiology in recent years. It stimulated interest in the question about the origin of life and its evolution. Here, we discuss what the roles of viruses might have been at the beginning of life and during evolution. Viruses are the most abundant biological entities on Earth. They are present everywhere, in our surrounding, the oceans, the soil and in every living being. Retroviruses contributed to about half of our genomic sequences and to the evolution of the mammalian placenta. Contemporary viruses reflect evolution ranging from the RNA world to the DNA-protein world. How far back can we trace their contribution? Earliest replicating and evolving entities are the ribozymes or viroids fulfilling several criteria of life. RNA can perform many aspects of life and influences our gene expression until today. The simplest structures with non-protein-coding information may represent models of life built on structural, not genetic information. Viruses today are obligatory parasites depending on host cells. Examples of how an independent lifestyle might have been lost include mitochondria, chloroplasts, Rickettsia and others, which used to be autonomous bacteria and became intracellular parasites or endosymbionts, thereby losing most of their genes. Even in vitro the loss of genes can be recapitulated all the way from coding to non-coding RNA. Furthermore, the giant viruses may indicate that there is no sharp border between living and non-living entities but an evolutionary continuum. Here, it is discussed how viruses can lose and gain genes, and that they are essential drivers of evolution. This discussion may stimulate the thinking about viruses as early possible forms of life. Apart from our view “viruses first”, there are others such as “proteins first” and “metabolism first.”",2019 Mar 19,"['Moelling, Karin', 'Broecker, Felix']",Front Microbiol,,,True
2a8e26038c98efac0a61629aa6b768fefad5a573,PMC,Fish Autophagy Protein 5 Exerts Negative Regulation on Antiviral Immune Response Against Iridovirus and Nodavirus,http://dx.doi.org/10.3389/fimmu.2019.00517,PMC6433989,30941145,CC BY,"Autophagy is an important biological activity that maintains homeostasis in eukaryotic cells. However, little is known about the functions of fish autophagy-related genes (Atgs). In this study, we cloned and characterized Atg5, a key gene in the autophagy gene superfamily, from orange-spotted grouper (Epinephelus coioides) (EcAtg5). EcAtg5 encoded a 275-amino acid protein that shared 94 and 81% identity to seabass (Lates calcarifer) and humans (Homo sapiens), respectively. The transcription level of EcAtg5 was significantly increased in cells infected with red-spotted grouper nervous necrosis virus (RGNNV). In cells infected with Singapore grouper iridovirus (SGIV), EcAtg5 expression declined during the early stage of infection and increased in the late stage. Fluorescence microscopy revealed that EcAtg5 mainly localized with a dot-like pattern in the cytoplasm of grouper cells. Overexpression of EcAtg5 significantly increased the replication of RGNNV and SGIV at different levels of detection, as indicated by increased severity of the cytopathic effect, transcription levels of viral genes, and levels of viral proteins. Knockdown of EcAtg5 decreased the replication of RGNNV and SGIV. Further studies showed that overexpression EcAtg5 activated autophagy, decreased expression levels of interferon related cytokines or effectors and pro-inflammatory factors, and inhibited the activation of nuclear factor κB, IFN-sensitive response element, and IFNs. In addition, ectopic expression of EcAtg5 affected cell cycle progression by hindering the G1/S transition. Taken together, our results demonstrated that fish Atg5 exerted a crucial role in virus replication by promoting autophagy, down-regulating antiviral IFN responses, and affecting the cell cycle.",2019 Mar 19,"['Li, Chen', 'Liu, Jiaxin', 'Zhang, Xin', 'Wei, Shina', 'Huang, Xiaohong', 'Huang, Youhua', 'Wei, Jingguang', 'Qin, Qiwei']",Front Immunol,,,True
d86146bbcb9ae18278150f4cb241ca1ce31fbf28,PMC,Drug Repurposing Approaches for the Treatment of Influenza Viral Infection: Reviving Old Drugs to Fight Against a Long-Lived Enemy,http://dx.doi.org/10.3389/fimmu.2019.00531,PMC6434107,30941148,CC BY,"Influenza viruses still constitute a real public health problem today. To cope with the emergence of new circulating strains, but also the emergence of resistant strains to classic antivirals, it is necessary to develop new antiviral approaches. This review summarizes the state-of-the-art of current antiviral options against influenza infection, with a particular focus on the recent advances of anti-influenza drug repurposing strategies and their potential therapeutic, regulatory and economic benefits. The review will illustrate the multiple ways to reposition molecules for the treatment of influenza, from adventitious discovery to in silico-based screening. These novel antiviral molecules, many of which targeting the host cell, in combination with conventional antiviral agents targeting the virus, will ideally enter the clinics and reinforce the therapeutic arsenal to combat influenza virus infections.",2019 Mar 19,"['Pizzorno, Andrés', 'Padey, Blandine', 'Terrier, Olivier', 'Rosa-Calatrava, Manuel']",Front Immunol,,,True
421bd6f23db8177832f8476dc64df824b7c2b017,PMC,Selection of reference genes for the quantitative real-time PCR normalization of gene expression in Isatis indigotica fortune,http://dx.doi.org/10.1186/s12867-019-0126-y,PMC6434783,30909859,CC BY,"BACKGROUND: Isatis indigotica, a traditional Chinese medicine, produces a variety of active ingredients. However, little is known about the key genes and corresponding expression profiling involved in the biosynthesis pathways of these ingredients. Quantitative real-time polymerase chain reaction (qRT-PCR) is a powerful, commonly-used method for gene expression analysis, but the accuracy of the quantitative data produced depends on the appropriate selection of reference genes. RESULTS: In this study, the systematic analysis of the reference genes was performed for quantitative real-Time PCR normalization in I. indigotica. We selected nine candidate reference genes, including six traditional housekeeping genes (ACT, α-TUB, β-TUB, UBC, CYP, and EF1-α), and three newly stable internal control genes (MUB, TIP41, and RPL) from a transcriptome dataset of I. indigotica, and evaluated their expression stabilities in different tissues (root, stem, leaf, and petiole) and leaves exposed to three abiotic treatments (low-nitrogen, ABA, and MeJA) using geNorm, NormFinder, BestKeeper, and comprehensive RefFind algorithms. The results demonstrated that MUB and EF1-α were the two most stable reference genes for all samples. TIP41 as the optimal reference gene for low-nitrogen stress and MeJA treatment, while ACT had the highest ranking for ABA treatment and CYP was the most suitable for different tissues. CONCLUSIONS: The results revealed that the selection and validation of appropriate reference genes for normalizing data is mandatory to acquire accurate quantification results. The necessity of specific internal control for specific conditions was also emphasized. Furthermore, this work will provide valuable information to enhance further research in gene function and molecular biology on I. indigotica and other related species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12867-019-0126-y) contains supplementary material, which is available to authorized users.",2019 Mar 25,"['Qu, Renjun', 'Miao, Yujing', 'Cui, Yingjing', 'Cao, Yiwen', 'Zhou, Ying', 'Tang, Xiaoqing', 'Yang, Jie', 'Wang, Fangquan']",BMC Mol Biol,,,True
43fd9e9fa6ecb2ec700c15288e7e3c7ba38f26a2,PMC,Leishmania infantum-specific IFN-γ production in stimulated blood from cats living in areas where canine leishmaniosis is endemic,http://dx.doi.org/10.1186/s13071-019-3386-y,PMC6434818,30909952,CC BY,"BACKGROUND: Feline leishmaniosis caused by Leishmania infantum is considered a rare disease in endemic areas, whereas subclinical infections are common. Immune response plays a key role in driving the course of L. infantum infection in other host species; however, the feline cell-mediated immune response to L. infantum infection has not yet been investigated. The aim of this study was to determine the cell-mediated immune response specific to L. infantum by means of interferon (IFN)-γ release in whole blood assay from cats living in endemic areas (66 in Sicily and 113 in Catalonia) and to compare with antibody levels to L. infantum [enzyme-linked immunosorbent assay (ELISA) and immunofluorescence antibody test (IFAT)], blood parasite load and retroviral infections. RESULTS: Most cats (n = 140) were L. infantum antibody negative and only 22% (n = 39) were positive. Only 9 and 2% of tested cats had a feline immunodeficency virus (FIV) infection or a feline leukemia virus (FeLV) infection, respectively. Thirty-two cats out of 179 (18%) produced IFN-γ after stimulation with L. infantum soluble antigen (LSA) while the majority of cats (93%) produced IFN-γ after stimulation with concanavalin A (ConA). Six LSA-IFN-γ-producer cats were seropositive (three to ELISA and five to IFAT) but they were polymerase chain reaction (PCR) negative, while only one cat was antibody- and PCR-positive. Significant positive correlations were found between IFN-γ concentrations after stimulation with LSA and ConA, and between serology and PCR testing. No association was found between FIV status and LSA or ConA-IFN-γ production. Combining PCR, serology and specific IFN-γ concentration results, we found that 36% of cats studied were exposed to L. infantum. CONCLUSIONS: As expected, cats from endemic areas produce IFN-γ after ex vivo blood stimulation with LSA and therefore are able to activate a cell-mediated adaptive immune response against the parasite that is variably associated with antibody or blood PCR positivity. The association of this assay to serological and molecular tests provides a better estimate of cat exposure to L. infantum.",2019 Mar 26,"['Priolo, Vito', 'Martínez-Orellana, Pamela', 'Pennisi, Maria Grazia', 'Masucci, Marisa', 'Prandi, David', 'Ippolito, Dorotea', 'Bruno, Federica', 'Castelli, Germano', 'Solano-Gallego, Laia']",Parasit Vectors,,,True
b1cb9713cb3f669a5f4b63e04395fb4669312d5b,PMC,A DNA Vaccine Encoding the VAA Gene of Vibrio anguillarum Induces a Protective Immune Response in Flounder,http://dx.doi.org/10.3389/fimmu.2019.00499,PMC6435001,30941134,CC BY,"Vibrio anguillarum is a pathogenic bacterium that infects flounder resulting in significant losses in the aquaculture industry. The VAA protein previously identified in flounder is associated with a role in immune protection within these fish. In the present study, a recombinant DNA plasmid encoding the VAA gene of V. anguillarum was constructed and its potential as a DNA vaccine, to prevent the infection of V. anguillarum in flounder fish, investigated. We verified the expression of the VAA protein both in vitro in cell lines and in vivo in flounder fish. The protective effects of pcDNA3.1-VAA (pVAA) were analyzed by determination of the percentage of sIgM(+), CD4-1(+), CD4-2(+), CD8β(+) lymphocytes, and the production of VAA-specific antibodies in flounder following their immunization with the DNA vaccine. Histopathological changes in immune related tissues, bacterial load, and relative percentage survival rates of flounder post-challenge with V. anguillarum, were all investigated to assess the efficacy of the pVAA DNA vaccine candidate. Fish intramuscularly immunized with pVAA showed a significant increase in CD4-1(+), CD4-2(+), and CD8β(+) T lymphocytes at days 9, 11, and 14 post-vaccination, reaching peak T-cell levels at days 11 or 14 post-immunization. The percentage of sIgM(+) lymphocytes reached peak levels at weeks 4–5 post-immunization. Specific anti-V. anguillarum or anti-rVAA antibodies were induced in inoculated fish at days 28–35 post-immunization. The liver of vaccinated flounder exhibited only slight histopathological changes compared with a significant pathology observed in control immunized fish. Additionally, a lower bacterial burden in the liver, spleen, and kidney were observed in pVAA protected fish in response to bacterial challenge, compared with pcDNA3.1 vector control injected fish. Moreover, the pVAA vaccine confers a relative percentage survival of 50.00% following V. anguillarum infection. In summary, this is the first study indicating an initial induction of the T lymphocyte response, followed by B lymphocyte induction of specific antibodies as a result of DNA immunization of flounder. This signifies the important potential of pVAA as a DNA vaccine candidate for the control of V. anguillarum infection.",2019 Mar 19,"['Xing, Jing', 'Xu, Hongsen', 'Tang, Xiaoqian', 'Sheng, Xiuzhen', 'Zhan, Wenbin']",Front Immunol,,,True
f5f2eb53666c84eb688a501f5042f1147440a7ad,PMC,Drug screening with human SMN2 reporter identifies SMN protein stabilizers to correct SMA pathology,http://dx.doi.org/10.26508/lsa.201800268,PMC6435041,30910806,CC BY,"Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, is caused by reduced levels of functional survival motor neuron (SMN) protein. To identify therapeutic agents for SMA, we established a versatile SMN2-GFP reporter line by targeting the human SMN2 gene. We then screened a compound library and identified Z-FA-FMK as a potent candidate. Z-FA-FMK, a cysteine protease inhibitor, increased functional SMN through inhibiting the protease-mediated degradation of both full-length and exon 7–deleted forms of SMN. Further studies reveal that CAPN1, CAPN7, CTSB, and CTSL mediate the degradation of SMN proteins, providing novel targets for SMA. Notably, Z-FA-FMK mitigated mitochondriopathy and neuropathy in SMA patient–derived motor neurons and showed protective effects in SMA animal model after intracerebroventricular injection. E64d, another cysteine protease inhibitor which can pass through the blood–brain barrier, showed even more potent therapeutic effects after subcutaneous delivery to SMA mice. Taken together, we have successfully established a human SMN2 reporter for future drug discovery and identified the potential therapeutic value of cysteine protease inhibitors in treating SMA via stabilizing SMN proteins.",2019 Mar 25,"['Wang, Yiran', 'Xu, Chongchong', 'Ma, Lin', 'Mou, Yongchao', 'Zhang, Bowen', 'Zhou, Shanshan', 'Tian, Yue', 'Trinh, Jessica', 'Zhang, Xiaoqing', 'Li, Xue-Jun']",Life Sci Alliance,,,True
528641560911ad9dcdcd6f443f6d09885017b3f8,PMC,Drug screening with human SMN2 reporter identifies SMN protein stabilizers to correct SMA pathology,http://dx.doi.org/10.26508/lsa.201800268,PMC6435041,30910806,CC BY,"Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, is caused by reduced levels of functional survival motor neuron (SMN) protein. To identify therapeutic agents for SMA, we established a versatile SMN2-GFP reporter line by targeting the human SMN2 gene. We then screened a compound library and identified Z-FA-FMK as a potent candidate. Z-FA-FMK, a cysteine protease inhibitor, increased functional SMN through inhibiting the protease-mediated degradation of both full-length and exon 7–deleted forms of SMN. Further studies reveal that CAPN1, CAPN7, CTSB, and CTSL mediate the degradation of SMN proteins, providing novel targets for SMA. Notably, Z-FA-FMK mitigated mitochondriopathy and neuropathy in SMA patient–derived motor neurons and showed protective effects in SMA animal model after intracerebroventricular injection. E64d, another cysteine protease inhibitor which can pass through the blood–brain barrier, showed even more potent therapeutic effects after subcutaneous delivery to SMA mice. Taken together, we have successfully established a human SMN2 reporter for future drug discovery and identified the potential therapeutic value of cysteine protease inhibitors in treating SMA via stabilizing SMN proteins.",2019 Mar 25,"['Wang, Yiran', 'Xu, Chongchong', 'Ma, Lin', 'Mou, Yongchao', 'Zhang, Bowen', 'Zhou, Shanshan', 'Tian, Yue', 'Trinh, Jessica', 'Zhang, Xiaoqing', 'Li, Xue-Jun']",Life Sci Alliance,,,True
825b65e57d2aa49eb507cf377561ce4ea950c644,PMC,Adaptive memory and evolution of the human naturalistic mind: Insights from the use of medicinal plants,http://dx.doi.org/10.1371/journal.pone.0214300,PMC6435313,30913230,CC BY,"Throughout evolutionary history, humans have been exposed to a wide variety of diseases, some of which have serious and even lethal consequences. Memorizing medicinal plants for the treatment of serious diseases likely maximized the chances of survival and reproduction and was instrumental in the evolutionary success of our species. In the present study, we used the idea of adaptive memory to understand whether human memory evolved to recall information about medicinal plants for the treatment of serious diseases. We considered plant-disease pairs of words as units of information available in a medical system based on the use of medicinal plants. The pairs included in the categories of chronic infectious diseases and transmissible infectious diseases were considered to be of higher adaptive value, whereas those included in the category of common conditions were considered to be of lower adaptive value. Pairs grouped into the category of emerging and reemerging diseases were employed to investigate conformity bias; pairs belonging to the category esthetic uses were considered to be of little adaptive relevance and utilized as an experimental control. Our results revealed that plant-disease pairs associated with the category of common conditions, considered by us to be of lower severity and less adaptive relevance for humans, were better remembered and retained in the participants' memory. We believe that prior experience with common conditions and the frequency of these conditions in the population may have intensified the ability to remember the plant-disease pairs associated with this group of diseases.",2019 Mar 26,"['Henriques da Silva, Risoneide', 'Ferreira Júnior, Washington Soares', 'Muniz de Medeiros, Patrícia', 'Albuquerque, Ulysses Paulino']",PLoS One,,,True
232e85eda8060808405e79f0dbe13309eccddf58,PMC,Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin,http://dx.doi.org/10.1002/mbo3.651,PMC6436431,29877619,CC BY,"Plasmodium falciparum malaria is the most severe form of malaria with several complications. The malaria pigment‐hemozoin (Hz) is associated with severe anemia, cytokine dysfunction, and immunosuppression, thus making it an interesting target for developing new strategies for antimalarial therapy. Monocytes (MO) in circulation actively ingest Hz released by Plasmodium parasites and secrete pro‐ and anti‐inflammatory cytokines. M1 and M2 types represent the two major forms of MO/macrophages (MQ) with distinct phenotypes and opposing functions. Imbalance in the polarization of these types is reported in many infectious diseases. Though the association of Hz with immunosuppression is well documented, its role in activation of MO in context of M1/M2 phenotypes remains to be addressed. We report here that natural Hz drives human MO toward M2‐like phenotype as evidenced by the expression of M2 signature markers. Hz‐fed MO showed elevated transcript and secreted level of IL‐10, CCL17, CCL1, expression of mannose‐binding lectin receptor (CD206), and arginase activity. Hz attenuated HLA‐DR expression, nitric oxide, and reactive oxygen species production, which are the features of M1 phenotype. Our data also implicate the involvement of p38 MAPK, PI3K/AKT, and NF‐κB signaling pathways in skewing of Hz‐fed MO toward M2‐like type and suppression of mitogen‐stimulated lymphocyte proliferation. Importantly, antimalarial drugs—chloroquine and artemisinin—partially reversed activation of Hz‐induced MO toward M2‐like phenotype. Considering the limitations in the current therapeutic options for malaria, we propose that these drugs may be re‐examined for their potential as immunomodulators and candidates for adjunctive treatment in malaria.",2018 Jun 7,"['Bobade, Deepali', 'Khandare, Ashwin V.', 'Deval, Mangesh', 'Shastry, Padma', 'Deshpande, Prakash']",Microbiologyopen,,,True
c850a9040414008da523d4ca13b8e61b36e0d98b,PMC,Antagonism of dsRNA-Induced Innate Immune Pathways by NS4a and NS4b Accessory Proteins during MERS Coronavirus Infection,http://dx.doi.org/10.1128/mBio.00319-19,PMC6437052,30914508,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in 2012 as a novel etiological agent of severe respiratory disease in humans. As during infection by other viruses, host sensing of viral double-stranded RNA (dsRNA) induces several antiviral pathways. These include interferon (IFN), oligoadenylate synthetase (OAS)-RNase L, and protein kinase R (PKR). Coronaviruses, including MERS-CoV, potently suppress the activation of these pathways, inducing only modest host responses. Our study describes the functions of two accessory proteins unique to MERS-CoV and related viruses, NS4a and NS4b, during infection in human airway epithelium-derived A549 cells. NS4a has been previously characterized as a dsRNA binding protein, while NS4b is a 2′,5′-phosphodiesterase with structural and enzymatic similarity to NS2 encoded by mouse hepatitis virus (MHV). We found that deletion of NS4a results in increased interferon lambda (IFNL1) expression, as does mutation of either the catalytic site or nuclear localization sequence of NS4b. All of the mutant viruses we tested exhibited slight decreases in replication. We previously reported that, like MHV NS2, NS4b antagonizes OAS-RNase L, but suppression of IFN is a previously unidentified function for viral phosphodiesterases. Unexpectedly, deletion of NS4a does not result in robust activation of the PKR or OAS-RNase L pathways. Therefore, MERS-CoV likely encodes other proteins that contribute to suppression or evasion of these antiviral innate immune pathways that should be an important focus of future work. This study provides additional insight into the complex interactions between MERS-CoV and the host immune response.",2019 Mar 26,"['Comar, Courtney E.', 'Goldstein, Stephen A.', 'Li, Yize', 'Yount, Boyd', 'Baric, Ralph S.', 'Weiss, Susan R.']",mBio,,,True
ff220214e91fabc8d302d1605cd9bac44fac507f,PMC,The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis,http://dx.doi.org/10.1186/s13054-019-2395-8,PMC6437920,30917856,CC BY,"BACKGROUND: The effect of corticosteroids on clinical outcomes in patients with influenza pneumonia remains controversial. We aimed to further evaluate the influence of corticosteroids on mortality in adult patients with influenza pneumonia by comparing corticosteroid-treated and placebo-treated patients. METHODS: The PubMed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and Information Sciences Institute (ISI) Web of Science databases were searched for all controlled studies that compared the effects of corticosteroids and placebo in adult patients with influenza pneumonia. The primary outcome was mortality, and the secondary outcomes were mechanical ventilation (MV) days, length of stay in the intensive care unit (ICU LOS), and the rate of secondary infection. RESULTS: Ten trials involving 6548 patients were pooled in our final analysis. Significant heterogeneity was found in all outcome measures except for ICU LOS (I(2) = 38%, P = 0.21). Compared with placebo, corticosteroids were associated with higher mortality (risk ratio [RR] 1.75, 95% confidence interval [CI] 1.30 ~ 2.36, Z = 3.71, P = 0.0002), longer ICU LOS (mean difference [MD] 2.14, 95% CI 1.17 ~ 3.10, Z = 4.35, P < 0.0001), and a higher rate of secondary infection (RR 1.98, 95% CI 1.04 ~ 3.78, Z = 2.08, P = 0.04) but not MV days (MD 0.81, 95% CI − 1.23 ~ 2.84, Z = 0.78, P = 0.44) in patients with influenza pneumonia. CONCLUSIONS: In patients with influenza pneumonia, corticosteroid use is associated with higher mortality. TRIAL REGISTRATION: PROSPERO (ID: CRD42018112384). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13054-019-2395-8) contains supplementary material, which is available to authorized users.",2019 Mar 27,"['Ni, Yue-Nan', 'Chen, Guo', 'Sun, Jiankui', 'Liang, Bin-Miao', 'Liang, Zong-An']",Crit Care,,,True
f533213ea544502d4d5aee4e6fabea7b1f0ceabc,PMC,Synthetic sulfonated derivatives of poly(allylamine hydrochloride) as inhibitors of human metapneumovirus,http://dx.doi.org/10.1371/journal.pone.0214646,PMC6438514,30921418,CC BY,"Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity. Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo. Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells. The results showed strong antiviral properties of NSPAHs. While the activity of NSPAHs is comparable to those of carrageenans, they show better physicochemical properties and may be delivered at high concentrations. The functional assays showed that tested polymers block hMPV release from infected cells and, consequently, constrain virus spread. Moreover, further studies on viruses utilizing different egress mechanisms suggest that observed antiviral effect depend on selective inhibition of viruses budding from the cell surface.",2019 Mar 28,"['Ciejka, Justyna', 'Botwina, Paweł', 'Nowakowska, Maria', 'Szczubiałka, Krzysztof', 'Pyrc, Krzysztof']",PLoS One,,,True
904202451061d0a1bca4dabde4623c09ca5e8033,PMC,Synthetic sulfonated derivatives of poly(allylamine hydrochloride) as inhibitors of human metapneumovirus,http://dx.doi.org/10.1371/journal.pone.0214646,PMC6438514,30921418,CC BY,"Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity. Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo. Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells. The results showed strong antiviral properties of NSPAHs. While the activity of NSPAHs is comparable to those of carrageenans, they show better physicochemical properties and may be delivered at high concentrations. The functional assays showed that tested polymers block hMPV release from infected cells and, consequently, constrain virus spread. Moreover, further studies on viruses utilizing different egress mechanisms suggest that observed antiviral effect depend on selective inhibition of viruses budding from the cell surface.",2019 Mar 28,"['Ciejka, Justyna', 'Botwina, Paweł', 'Nowakowska, Maria', 'Szczubiałka, Krzysztof', 'Pyrc, Krzysztof']",PLoS One,,,False
dfa661fc7e75c9cbda9afedfa89031ee25a794ef,PMC,Synthetic sulfonated derivatives of poly(allylamine hydrochloride) as inhibitors of human metapneumovirus,http://dx.doi.org/10.1371/journal.pone.0214646,PMC6438514,30921418,CC BY,"Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity. Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo. Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells. The results showed strong antiviral properties of NSPAHs. While the activity of NSPAHs is comparable to those of carrageenans, they show better physicochemical properties and may be delivered at high concentrations. The functional assays showed that tested polymers block hMPV release from infected cells and, consequently, constrain virus spread. Moreover, further studies on viruses utilizing different egress mechanisms suggest that observed antiviral effect depend on selective inhibition of viruses budding from the cell surface.",2019 Mar 28,"['Ciejka, Justyna', 'Botwina, Paweł', 'Nowakowska, Maria', 'Szczubiałka, Krzysztof', 'Pyrc, Krzysztof']",PLoS One,,,False
21cf8608658a43584820ee18f735e717a71519d4,PMC,Synthetic sulfonated derivatives of poly(allylamine hydrochloride) as inhibitors of human metapneumovirus,http://dx.doi.org/10.1371/journal.pone.0214646,PMC6438514,30921418,CC BY,"Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity. Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo. Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells. The results showed strong antiviral properties of NSPAHs. While the activity of NSPAHs is comparable to those of carrageenans, they show better physicochemical properties and may be delivered at high concentrations. The functional assays showed that tested polymers block hMPV release from infected cells and, consequently, constrain virus spread. Moreover, further studies on viruses utilizing different egress mechanisms suggest that observed antiviral effect depend on selective inhibition of viruses budding from the cell surface.",2019 Mar 28,"['Ciejka, Justyna', 'Botwina, Paweł', 'Nowakowska, Maria', 'Szczubiałka, Krzysztof', 'Pyrc, Krzysztof']",PLoS One,,,False
66e382f962bd81874f39371645ee495aa56347e8,PMC,Synthetic sulfonated derivatives of poly(allylamine hydrochloride) as inhibitors of human metapneumovirus,http://dx.doi.org/10.1371/journal.pone.0214646,PMC6438514,30921418,CC BY,"Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity. Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo. Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells. The results showed strong antiviral properties of NSPAHs. While the activity of NSPAHs is comparable to those of carrageenans, they show better physicochemical properties and may be delivered at high concentrations. The functional assays showed that tested polymers block hMPV release from infected cells and, consequently, constrain virus spread. Moreover, further studies on viruses utilizing different egress mechanisms suggest that observed antiviral effect depend on selective inhibition of viruses budding from the cell surface.",2019 Mar 28,"['Ciejka, Justyna', 'Botwina, Paweł', 'Nowakowska, Maria', 'Szczubiałka, Krzysztof', 'Pyrc, Krzysztof']",PLoS One,,,False
faaceb990fd3b8c02dfe7dd3b71aab0876f40255,PMC,Synthetic sulfonated derivatives of poly(allylamine hydrochloride) as inhibitors of human metapneumovirus,http://dx.doi.org/10.1371/journal.pone.0214646,PMC6438514,30921418,CC BY,"Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity. Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo. Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells. The results showed strong antiviral properties of NSPAHs. While the activity of NSPAHs is comparable to those of carrageenans, they show better physicochemical properties and may be delivered at high concentrations. The functional assays showed that tested polymers block hMPV release from infected cells and, consequently, constrain virus spread. Moreover, further studies on viruses utilizing different egress mechanisms suggest that observed antiviral effect depend on selective inhibition of viruses budding from the cell surface.",2019 Mar 28,"['Ciejka, Justyna', 'Botwina, Paweł', 'Nowakowska, Maria', 'Szczubiałka, Krzysztof', 'Pyrc, Krzysztof']",PLoS One,,,False
afeaf180e4767164482b4ba19581e847fa8cfacc,PMC,Synthetic sulfonated derivatives of poly(allylamine hydrochloride) as inhibitors of human metapneumovirus,http://dx.doi.org/10.1371/journal.pone.0214646,PMC6438514,30921418,CC BY,"Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity. Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo. Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells. The results showed strong antiviral properties of NSPAHs. While the activity of NSPAHs is comparable to those of carrageenans, they show better physicochemical properties and may be delivered at high concentrations. The functional assays showed that tested polymers block hMPV release from infected cells and, consequently, constrain virus spread. Moreover, further studies on viruses utilizing different egress mechanisms suggest that observed antiviral effect depend on selective inhibition of viruses budding from the cell surface.",2019 Mar 28,"['Ciejka, Justyna', 'Botwina, Paweł', 'Nowakowska, Maria', 'Szczubiałka, Krzysztof', 'Pyrc, Krzysztof']",PLoS One,,,False
33f4f3fb96f70b67540847a01924ccca6aac876c,PMC,Synthetic sulfonated derivatives of poly(allylamine hydrochloride) as inhibitors of human metapneumovirus,http://dx.doi.org/10.1371/journal.pone.0214646,PMC6438514,30921418,CC BY,"Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity. Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo. Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells. The results showed strong antiviral properties of NSPAHs. While the activity of NSPAHs is comparable to those of carrageenans, they show better physicochemical properties and may be delivered at high concentrations. The functional assays showed that tested polymers block hMPV release from infected cells and, consequently, constrain virus spread. Moreover, further studies on viruses utilizing different egress mechanisms suggest that observed antiviral effect depend on selective inhibition of viruses budding from the cell surface.",2019 Mar 28,"['Ciejka, Justyna', 'Botwina, Paweł', 'Nowakowska, Maria', 'Szczubiałka, Krzysztof', 'Pyrc, Krzysztof']",PLoS One,,,False
03ccecb9c291d5e8d7044d7855710690523b5152,PMC,Synthetic sulfonated derivatives of poly(allylamine hydrochloride) as inhibitors of human metapneumovirus,http://dx.doi.org/10.1371/journal.pone.0214646,PMC6438514,30921418,CC BY,"Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity. Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo. Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells. The results showed strong antiviral properties of NSPAHs. While the activity of NSPAHs is comparable to those of carrageenans, they show better physicochemical properties and may be delivered at high concentrations. The functional assays showed that tested polymers block hMPV release from infected cells and, consequently, constrain virus spread. Moreover, further studies on viruses utilizing different egress mechanisms suggest that observed antiviral effect depend on selective inhibition of viruses budding from the cell surface.",2019 Mar 28,"['Ciejka, Justyna', 'Botwina, Paweł', 'Nowakowska, Maria', 'Szczubiałka, Krzysztof', 'Pyrc, Krzysztof']",PLoS One,,,False
a4471f59c57d8e592587a62d976d540e54eff9a2,PMC,Synthetic sulfonated derivatives of poly(allylamine hydrochloride) as inhibitors of human metapneumovirus,http://dx.doi.org/10.1371/journal.pone.0214646,PMC6438514,30921418,CC BY,"Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity. Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo. Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells. The results showed strong antiviral properties of NSPAHs. While the activity of NSPAHs is comparable to those of carrageenans, they show better physicochemical properties and may be delivered at high concentrations. The functional assays showed that tested polymers block hMPV release from infected cells and, consequently, constrain virus spread. Moreover, further studies on viruses utilizing different egress mechanisms suggest that observed antiviral effect depend on selective inhibition of viruses budding from the cell surface.",2019 Mar 28,"['Ciejka, Justyna', 'Botwina, Paweł', 'Nowakowska, Maria', 'Szczubiałka, Krzysztof', 'Pyrc, Krzysztof']",PLoS One,,,False
5d295bdf0e26bc9492f3fb1580833419f26b4e7c,PMC,Endemicity and prevalence of multipartite viruses under heterogeneous between-host transmission,http://dx.doi.org/10.1371/journal.pcbi.1006876,PMC6438571,30883545,CC BY,"Multipartite viruses replicate through a puzzling evolutionary strategy. Their genome is segmented into two or more parts, and encapsidated in separate particles that appear to propagate independently. Completing the replication cycle, however, requires the full genome, so that a systemic infection of a host requires the concurrent presence of several particles. This represents an apparent evolutionary drawback of multipartitism, while its advantages remain unclear. A transition from monopartite to multipartite viral forms has been described in vitro under conditions of high multiplicity of infection, suggesting that cooperation between defective mutants is a plausible evolutionary pathway towards multipartitism. However, it is unknown how the putative advantages that multipartitism might enjoy at the microscopic level affect its epidemiology, or if an explicit advantange is needed to explain its ecological persistence. In order to disentangle which mechanisms might contribute to the rise and fixation of multipartitism, we here investigate the interaction between viral spreading dynamics and host population structure. We set up a compartmental model of the spread of a virus in its different forms and explore its epidemiology using both analytical and numerical techniques. We uncover that the impact of host contact structure on spreading dynamics entails a rich phenomenology of ecological relationships that includes cooperation, competition, and commensality. Furthermore, we find out that multipartitism might rise to fixation even in the absence of explicit microscopic advantages. Multipartitism allows the virus to colonize environments that could not be invaded by the monopartite form, while homogeneous contacts between hosts facilitate its spread. We conjecture that these features might have led to an increase in the diversity and prevalence of multipartite viral forms concomitantly with the expansion of agricultural practices.",2019 Mar 18,"['Valdano, Eugenio', 'Manrubia, Susanna', 'Gómez, Sergio', 'Arenas, Alex']",PLoS Comput Biol,,,True
d43a73492744f56383a502fdd4fdc36eb160e09e,PMC,Endemicity and prevalence of multipartite viruses under heterogeneous between-host transmission,http://dx.doi.org/10.1371/journal.pcbi.1006876,PMC6438571,30883545,CC BY,"Multipartite viruses replicate through a puzzling evolutionary strategy. Their genome is segmented into two or more parts, and encapsidated in separate particles that appear to propagate independently. Completing the replication cycle, however, requires the full genome, so that a systemic infection of a host requires the concurrent presence of several particles. This represents an apparent evolutionary drawback of multipartitism, while its advantages remain unclear. A transition from monopartite to multipartite viral forms has been described in vitro under conditions of high multiplicity of infection, suggesting that cooperation between defective mutants is a plausible evolutionary pathway towards multipartitism. However, it is unknown how the putative advantages that multipartitism might enjoy at the microscopic level affect its epidemiology, or if an explicit advantange is needed to explain its ecological persistence. In order to disentangle which mechanisms might contribute to the rise and fixation of multipartitism, we here investigate the interaction between viral spreading dynamics and host population structure. We set up a compartmental model of the spread of a virus in its different forms and explore its epidemiology using both analytical and numerical techniques. We uncover that the impact of host contact structure on spreading dynamics entails a rich phenomenology of ecological relationships that includes cooperation, competition, and commensality. Furthermore, we find out that multipartitism might rise to fixation even in the absence of explicit microscopic advantages. Multipartitism allows the virus to colonize environments that could not be invaded by the monopartite form, while homogeneous contacts between hosts facilitate its spread. We conjecture that these features might have led to an increase in the diversity and prevalence of multipartite viral forms concomitantly with the expansion of agricultural practices.",2019 Mar 18,"['Valdano, Eugenio', 'Manrubia, Susanna', 'Gómez, Sergio', 'Arenas, Alex']",PLoS Comput Biol,,,True
bb8a05062237c64d231f3ba922b8ec26c7f32eaa,PMC,"Proceedings of Réanimation 2019, the French Intensive Care Society International Congress",http://dx.doi.org/10.1186/s13613-018-0474-7,PMC6439134,30924032,CC BY,,2019 Mar 29,,Ann Intensive Care,,,True
6f1a0067a1612a8293e7cb64c89bf2e92b674fae,PMC,"Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms",http://dx.doi.org/10.3389/fneur.2019.00282,PMC6439316,30967837,CC BY,"Traumatic spinal cord injury (SCI) is a life changing neurological condition with substantial socioeconomic implications for patients and their care-givers. Recent advances in medical management of SCI has significantly improved diagnosis, stabilization, survival rate and well-being of SCI patients. However, there has been small progress on treatment options for improving the neurological outcomes of SCI patients. This incremental success mainly reflects the complexity of SCI pathophysiology and the diverse biochemical and physiological changes that occur in the injured spinal cord. Therefore, in the past few decades, considerable efforts have been made by SCI researchers to elucidate the pathophysiology of SCI and unravel the underlying cellular and molecular mechanisms of tissue degeneration and repair in the injured spinal cord. To this end, a number of preclinical animal and injury models have been developed to more closely recapitulate the primary and secondary injury processes of SCI. In this review, we will provide a comprehensive overview of the recent advances in our understanding of the pathophysiology of SCI. We will also discuss the neurological outcomes of human SCI and the available experimental model systems that have been employed to identify SCI mechanisms and develop therapeutic strategies for this condition.",2019 Mar 22,"['Alizadeh, Arsalan', 'Dyck, Scott Matthew', 'Karimi-Abdolrezaee, Soheila']",Front Neurol,,,True
8f25c12cb9bed748932b23030b88070649e67810,PMC,Visual tools to assess the plausibility of algorithm-identified infectious disease clusters: an application to mumps data from the Netherlands dating from January 2009 to June 2016,http://dx.doi.org/10.2807/1560-7917.ES.2019.24.12.1800331,PMC6440581,30914076,CC BY,"INTRODUCTION: With growing amounts of data available, identification of clusters of persons linked to each other by transmission of an infectious disease increasingly relies on automated algorithms. We propose cluster finding to be a two-step process: first, possible transmission clusters are identified using a cluster algorithm, second, the plausibility that the identified clusters represent genuine transmission clusters is evaluated. AIM: To introduce visual tools to assess automatically identified clusters. METHODS: We developed tools to visualise: (i) clusters found in dimensions of time, geographical location and genetic data; (ii) nested sub-clusters within identified clusters; (iii) intra-cluster pairwise dissimilarities per dimension; (iv) intra-cluster correlation between dimensions. We applied our tools to notified mumps cases in the Netherlands with available disease onset date (January 2009 – June 2016), geographical information (location of residence), and pathogen sequence data (n = 112). We compared identified clusters to clusters reported by the Netherlands Early Warning Committee (NEWC). RESULTS: We identified five mumps clusters. Three clusters were considered plausible. One was questionable because, in phylogenetic analysis, genetic sequences related to it segregated in two groups. One was implausible with no smaller nested clusters, high intra-cluster dissimilarities on all dimensions, and low intra-cluster correlation between dimensions. The NEWC reports concurred with our findings: the plausible/questionable clusters corresponded to reported outbreaks; the implausible cluster did not. CONCLUSION: Our tools for assessing automatically identified clusters allow outbreak investigators to rapidly spot plausible transmission clusters for mumps and other human-to-human transmissible diseases. This fast information processing potentially reduces workload.",2019 Mar 21,"['Soetens, Loes', 'Backer, Jantien A.', 'Hahné, Susan', 'van Binnendijk, Rob', 'Gouma, Sigrid', 'Wallinga, Jacco']",Euro Surveill,,,True
fa93d37191324ed24f52e766b7faa70039a79b92,PMC,Visual tools to assess the plausibility of algorithm-identified infectious disease clusters: an application to mumps data from the Netherlands dating from January 2009 to June 2016,http://dx.doi.org/10.2807/1560-7917.ES.2019.24.12.1800331,PMC6440581,30914076,CC BY,"INTRODUCTION: With growing amounts of data available, identification of clusters of persons linked to each other by transmission of an infectious disease increasingly relies on automated algorithms. We propose cluster finding to be a two-step process: first, possible transmission clusters are identified using a cluster algorithm, second, the plausibility that the identified clusters represent genuine transmission clusters is evaluated. AIM: To introduce visual tools to assess automatically identified clusters. METHODS: We developed tools to visualise: (i) clusters found in dimensions of time, geographical location and genetic data; (ii) nested sub-clusters within identified clusters; (iii) intra-cluster pairwise dissimilarities per dimension; (iv) intra-cluster correlation between dimensions. We applied our tools to notified mumps cases in the Netherlands with available disease onset date (January 2009 – June 2016), geographical information (location of residence), and pathogen sequence data (n = 112). We compared identified clusters to clusters reported by the Netherlands Early Warning Committee (NEWC). RESULTS: We identified five mumps clusters. Three clusters were considered plausible. One was questionable because, in phylogenetic analysis, genetic sequences related to it segregated in two groups. One was implausible with no smaller nested clusters, high intra-cluster dissimilarities on all dimensions, and low intra-cluster correlation between dimensions. The NEWC reports concurred with our findings: the plausible/questionable clusters corresponded to reported outbreaks; the implausible cluster did not. CONCLUSION: Our tools for assessing automatically identified clusters allow outbreak investigators to rapidly spot plausible transmission clusters for mumps and other human-to-human transmissible diseases. This fast information processing potentially reduces workload.",2019 Mar 21,"['Soetens, Loes', 'Backer, Jantien A.', 'Hahné, Susan', 'van Binnendijk, Rob', 'Gouma, Sigrid', 'Wallinga, Jacco']",Euro Surveill,,,False
3289d3f6963ba040c68dbbde3120156d73e1e5b4,PMC,Visual tools to assess the plausibility of algorithm-identified infectious disease clusters: an application to mumps data from the Netherlands dating from January 2009 to June 2016,http://dx.doi.org/10.2807/1560-7917.ES.2019.24.12.1800331,PMC6440581,30914076,CC BY,"INTRODUCTION: With growing amounts of data available, identification of clusters of persons linked to each other by transmission of an infectious disease increasingly relies on automated algorithms. We propose cluster finding to be a two-step process: first, possible transmission clusters are identified using a cluster algorithm, second, the plausibility that the identified clusters represent genuine transmission clusters is evaluated. AIM: To introduce visual tools to assess automatically identified clusters. METHODS: We developed tools to visualise: (i) clusters found in dimensions of time, geographical location and genetic data; (ii) nested sub-clusters within identified clusters; (iii) intra-cluster pairwise dissimilarities per dimension; (iv) intra-cluster correlation between dimensions. We applied our tools to notified mumps cases in the Netherlands with available disease onset date (January 2009 – June 2016), geographical information (location of residence), and pathogen sequence data (n = 112). We compared identified clusters to clusters reported by the Netherlands Early Warning Committee (NEWC). RESULTS: We identified five mumps clusters. Three clusters were considered plausible. One was questionable because, in phylogenetic analysis, genetic sequences related to it segregated in two groups. One was implausible with no smaller nested clusters, high intra-cluster dissimilarities on all dimensions, and low intra-cluster correlation between dimensions. The NEWC reports concurred with our findings: the plausible/questionable clusters corresponded to reported outbreaks; the implausible cluster did not. CONCLUSION: Our tools for assessing automatically identified clusters allow outbreak investigators to rapidly spot plausible transmission clusters for mumps and other human-to-human transmissible diseases. This fast information processing potentially reduces workload.",2019 Mar 21,"['Soetens, Loes', 'Backer, Jantien A.', 'Hahné, Susan', 'van Binnendijk, Rob', 'Gouma, Sigrid', 'Wallinga, Jacco']",Euro Surveill,,,True
9d047b01dc671b0c722c5cbdbc6f0d2ccb8481e4,PMC,"High Prevalence of Viral Infections Among Hospitalized Pneumonia Patients in Equatorial Sarawak, Malaysia",http://dx.doi.org/10.1093/ofid/ofz074,PMC6440682,30949525,CC BY,"BACKGROUND: Although pneumonia is a known cause of morbidity and mortality in Sarawak, Malaysia, the etiology and epidemiology of pneumonia are not well described in this equatorial region. Routine clinical diagnostics for pneumonia etiology at government hospitals in Sarawak had historically involved only bacterial diagnostics. Viral diagnostics were only obtained through outside consultations. METHODS: From June 15, 2017 to May 14, 2018, we collected nasopharyngeal swabs from 600 patients of all ages older than 1 month hospitalized with pneumonia at Sibu and Kapit Hospitals. Specimens were examined at our collaborating institutions with a panel of molecular assays for viral pathogens including influenza A (IAV), IBV, ICV, and IDV, human adenovirus (AdV), human enterovirus (EV), human coronavirus (CoV), respiratory syncytial virus subtype A (RSV-A) or RSV-B, and parainfluenza virus (PIV) types 1–4. RESULTS: Of 599 samples examined, 288 (48%) had molecular evidence of 1 or more respiratory viruses. Overall, the most prevalent virus detected was RSV-A (14.2%) followed by AdV (10.4%) and IAV (10.4%), then RSV-B (6.2%), EV (4.2%), IBV (2.2%), PIV-3 (1.7%), CoV (1.0%), PIV-1 (1.0%), PIV-4 (0.7%), and PIV-2 (0.2%). No specimens were confirmed positive for ICV or IDV. CONCLUSIONS: The high prevalence of viruses detected in this study suggest that respiratory viruses may be responsible for considerable morbidity in equatorial regions such as Sarawak. Access to viral diagnostics are very necessary for medical staff to determine appropriate pneumonia treatments.",2019 Feb 13,"['Toh, Teck-Hock', 'Hii, King-Ching', 'Fieldhouse, Jane K', 'Ting, Jakie', 'Berita, Antoinette', 'Nguyen, Tham Thi', 'Wong, See-Chang', 'Wong, Toh-Mee', 'Lim, Wei-Honn', 'Ha, Siaw-Jing', 'Lau, Chuet-Zou', 'Kong, Sing-Ling', 'Bailey, Emily S', 'Warkentien, Tyler E', 'Husain, Tupur S', 'Gray, Gregory C']",Open Forum Infect Dis,,,True
095cf0472e7f23349f22a1f538eb2c8d590d33e1,PMC,Clinical characteristics and outcomes of patients with severe acute respiratory infections (SARI): results from the Egyptian surveillance study 2010–2014,http://dx.doi.org/10.1186/s40248-019-0174-7,PMC6442424,30976418,CC BY,"BACKGROUND: Respiratory viral and atypical bacterial infections data in Egyptian patients are sparse. This study describes the clinical features and outcomes of patients with severe acute respiratory infections (SARI) in hospitalized patients in Egypt. METHODS: SARI surveillance was implemented at Cairo University Hospital (CUH) during the period 2010–2014. All hospitalized patients meeting the WHO case definition for SARI were enrolled. Nasopharyngeal/oropharyngeal (NP/OP) swabs were collected and samples were tested using RT-PCR for influenza A, B, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), parainfluenza virus (PIV 1,2,3,4), adenovirus, bocavirus, coronavirus, enterovirus, rhinovirus, and atypical bacteria. Data were analyzed to calculate positivity rates for viral pathogens and determine which pathogens related to severe outcomes or resulted in death. RESULTS: Overall, 1,075/3,207 (33.5%) cases had a viral etiology, with a mean age of 5.74 (±13.87) years. The highest rates were reported for RSV (485 cases, 45.2%), PIV (125, 11.6%), and adenovirus (105, 9.8%). Children had a higher viral rate (981, 91.2%) compared to 94 (8.8%) cases in adults. Patients with identified viruses had significantly lower rates for ICU admission, hospital stay, mechanical ventilation, and overall mortality than those without identified viruses. No infections were independently associated with severe outcomes. CONCLUSIONS: Viral pathogens were encountered in one-third of hospitalized adult and pediatric Egyptian patients with SARI, while atypical bacteria had a minor role. Highest rates of viral infections were reported for RSV, PIV, and adenovirus. Viral infections had neither negative impacts on clinical features nor outcomes of patients with SARI in our locality.",2019 Apr 1,"['Hatem, Ashraf', 'Mohamed, Sherif', 'Abu Elhassan, Usama E.', 'Ismael, Eman A. M.', 'Rizk, Magda S.', 'El-kholy, Amany', 'El-Harras, Mohamed']",Multidiscip Respir Med,,,True
aaa7d4e5136a4175368222cba1f76b0a33f5a688,PMC,"The Role of Microglia in Bacterial Meningitis: Inflammatory Response, Experimental Models and New Neuroprotective Therapeutic Strategies",http://dx.doi.org/10.3389/fmicb.2019.00576,PMC6442515,30967852,CC BY,"Microglia have a pivotal role in the pathophysiology of bacterial meningitis. The goal of this review is to provide an overview on how microglia respond to bacterial pathogens targeting the brain, how the interplay between microglia and bacteria can be studied experimentally, and possible ways to use gained knowledge to identify novel preventive and therapeutic strategies. We discuss the dual role of microglia in disease development, the beneficial functions crucial for bacterial clearing, and the destructive properties through triggering neuroinflammation, characterized by cytokine and chemokine release which leads to leukocyte trafficking through the brain vascular endothelium and breakdown of the blood-brain barrier integrity. Due to intrinsic complexity of microglia and up until recently lack of specific markers, the study of microglial response to bacterial pathogens is challenging. New experimental models and techniques open up possibilities to accelerate progress in the field. We review existing models and discuss possibilities and limitations. Finally, we summarize recent findings where bacterial virulence factors are identified to be important for the microglial response, and how manipulation of evoked responses could be used for therapeutic or preventive purposes. Among promising approaches are: modulations of microglia phenotype switching toward anti-inflammatory and phagocytic functions, the use of non-bacterolytic antimicrobials, preventing release of bacterial components into the neural milieu and consequential amplification of immune activation, and protection of the blood-brain barrier integrity.",2019 Mar 25,"['Thorsdottir, Sigrun', 'Henriques-Normark, Birgitta', 'Iovino, Federico']",Front Microbiol,,,True
55322bfc591eeae6d68a9826baaebf6ec74234ca,PMC,Negative Immunomodulatory Effects of Type 2 Porcine Reproductive and Respiratory Syndrome Virus-Induced Interleukin-1 Receptor Antagonist on Porcine Innate and Adaptive Immune Functions,http://dx.doi.org/10.3389/fimmu.2019.00579,PMC6443931,30972072,CC BY,"Impaired innate and adaptive immune responses are evidenced throughout the course of PRRSV infection. We previously reported that interleukin-1 receptor antagonist (IL-1Ra) was involved in PRRSV-induced immunosuppression during an early phase of infection. However, the exact mechanism associated with PRRSV-induced IL-1Ra immunomodulation remains unknown. To explore the immunomodulatory properties of PRRSV-induced IL-1Ra on porcine immune functions, monocyte-derived dendritic cells (MoDC) and leukocytes were cultured with type 2 PRRSV, and the immunological role of IL-1Ra was assessed by addition of anti-porcine IL-1Ra Ab. The results demonstrated that PRRSV-induced IL-1Ra reduced phagocytosis, surface expression of MHC II (SLA-DR) and CD86, as well as downregulation of IFNA and IL1 gene expression in the MoDC culture system. Interestingly, IL-1Ra secreted by the PRRSV-infected MoDC also inhibited T lymphocyte differentiation and proliferation, but not IFN-γ production. Although PRRSV-induced IL-1Ra was not directly linked to IL-10 production, it contributed to the differentiation of regulatory T lymphocytes (Treg) within the culture system. Taken together, our results demonstrated that PRRSV-induced IL-1Ra downregulates innate immune functions, T lymphocyte differentiation and proliferation, and influences collectively with IL-10 in the Treg induction. The immunomodulatory roles of IL-1Ra elucidated in this study increase our understanding of the immunobiology of PRRSV.",2019 Mar 26,"['Nedumpun, Teerawut', 'Techakriengkrai, Navapon', 'Thanawongnuwech, Roongroje', 'Suradhat, Sanipa']",Front Immunol,,,True
897261feca5f934f8a39599d294f9147941bfcad,PMC,Community Health Workers and Pandemic Preparedness: Current and Prospective Roles,http://dx.doi.org/10.3389/fpubh.2019.00062,PMC6443984,30972316,CC BY,"Despite the importance of community health workers (CHWs) to health systems in resource-constrained environments, relatively little has been written about their contributions to pandemic preparedness. In this perspective piece, we draw from the response to the 2014 Ebola and 2015 Zika epidemics to review examples whereby CHWs contributed to health security and pandemic preparedness. CHWs promoted pandemic preparedness prior to the epidemics by increasing the access to health services and products within communities, communicating health concepts in a culturally appropriate fashion, and reducing the burdens felt by formal healthcare systems. During the epidemics, CHWs promoted pandemic preparedness by acting as community-level educators and mobilizers, contributing to surveillance systems, and filling health service gaps. Acknowledging the success CHWs have had in these roles and in previous interventions, we propose that the cadre may be better engaged in pandemic preparedness in the future. Some practical strategies for achieving this include training and using CHWs to communicate One Health information to at-risk communities prior to outbreaks, pooling them into a reserve health corps to be used during public health emergencies, and formalizing agreements and strategies to promote the early engagement of CHWs in response actions. Recognizing that CHWs already play a role in pandemic preparedness, we feel that expanding the roles and responsibilities of CHWs represents a practical means of improving pandemic and community-level resilience.",2019 Mar 26,"['Boyce, Matthew R.', 'Katz, Rebecca']",Front Public Health,,,True
f91df0d67f4d6fc329815c233f76b5ef0dd3876a,PMC,The politics and ethics of hospital infection prevention and control: a qualitative case study of senior clinicians’ perceptions of professional and cultural factors that influence doctors’ attitudes and practices in a large Australian hospital,http://dx.doi.org/10.1186/s12913-019-4044-y,PMC6444390,30940153,CC BY,"BACKGROUND: Hospital infection prevention and control (IPC) programs are designed to minimise rates of preventable healthcare-associated infection (HAI) and acquisition of multidrug resistant organisms, which are among the commonest adverse effects of hospitalisation. Failures of hospital IPC in recent years have led to nosocomial and community outbreaks of emerging infections, causing preventable deaths and social disruption. Therefore, effective IPC programs are essential, but can be difficult to sustain in busy clinical environments. Healthcare workers’ adherence to routine IPC practices is often suboptimal, but there is evidence that doctors, as a group, are consistently less compliant than nurses. This is significant because doctors’ behaviours disproportionately influence those of other staff and their peripatetic practice provides more opportunities for pathogen transmission. A better understanding of what drives doctors’ IPC practices will contribute to development of new strategies to improve IPC, overall. METHODS: This qualitative case study involved in-depth interviews with senior clinicians and clinician-managers/directors (16 doctors and 10 nurses) from a broad range of specialties, in a large Australian tertiary hospital, to explore their perceptions of professional and cultural factors that influence doctors’ IPC practices, using thematic analysis of data. RESULTS: Professional/clinical autonomy; leadership and role modelling; uncertainty about the importance of HAIs and doctors’ responsibilities for preventing them; and lack of clarity about senior consultants’ obligations emerged as major themes. Participants described marked variation in practices between individual doctors, influenced by, inter alia, doctors’ own assessment of patients’ infection risk and their beliefs about the efficacy of IPC policies. Participants believed that most doctors recognise the significance of HAIs and choose to [mostly] observe organisational IPC policies, but a minority show apparent contempt for accepted rules, disrespect for colleagues who adhere to, or are expected to enforce, them and indifference to patients whose care is compromised. CONCLUSIONS: Failure of healthcare and professional organisations to address doctors’ poor IPC practices and unprofessional behaviour, more generally, threatens patient safety and staff morale and undermines efforts to minimise the risks of dangerous nosocomial infection.",2019 Apr 2,"['Gilbert, Gwendolyn L.', 'Kerridge, Ian']",BMC Health Serv Res,,,True
965583d97eb6d8834e301978f5c91443efa7780d,PMC,Revitalization of integrated disease surveillance and response in Sierra Leone post Ebola virus disease outbreak,http://dx.doi.org/10.1186/s12889-019-6636-1,PMC6444503,30940125,CC BY,"BACKGROUND: The Ministry of Health and Sanitation (MOHS) in Sierra Leone partially rolled out the implementation of Integrated Disease Surveillance and Response (IDSR) in 2003. After the Ebola virus disease outbreak in 2014–2015, there was need to strengthen IDSR to ensure prompt detection and response to epidemic-prone diseases. We describe the processes, successes and challenges of revitalizing public health surveillance in a country recovering from a protracted Ebola virus disease outbreak. METHODS: The revitalization process began with adaptation of the revised IDSR guidelines and development of customized guidelines to suit the health care systems in Sierra Leone. Public health experts defined data flow, system operations, case definitions, frequency and channels of reporting and dissemination. Next, phased training of IDSR focal persons in each health facility and the distribution of data collection and reporting tools was done. Monitoring activities included periodic supportive supervision and data quality assessments. Rapid response teams were formed to investigate and respond to disease outbreak alerts in all districts. RESULTS: Submission of reports through the IDSR system began in mid-2015 and by the 35th epidemiologic week, all district health teams were submitting reports. The key performance indicators measuring the functionality of the IDSR system in 2016 and 2017 were achieved (WHO Africa Region target ≥80%); the annual average proportion of timely weekly health facility reports submitted to the next level was 93% in 2016 and 97% in 2017; the proportion of suspected outbreaks and public health events detected through the IDSR system was 96% (n = 87) in 2016 and 100% (n = 85) in 2017. CONCLUSION: With proper planning, phased implementation and adequate investment of resources, it is possible to establish a functional IDSR system in a country recovering from a public health crisis. A functional IDSR system requires well trained workforce, provision of the necessary tools and guidelines, information, communication and technology infrastructure to support data transmission, provision of timely feedback as well as logistical support. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-019-6636-1) contains supplementary material, which is available to authorized users.",2019 Apr 2,"['Njuguna, Charles', 'Jambai, Amara', 'Chimbaru, Alexander', 'Nordstrom, Anders', 'Conteh, Roland', 'Latt, Anderson', 'O-tipo, Shikanga', 'Musoke, Robert', 'Githuku, Jane', 'Yoti, Zablon', 'Yahaya, Ali', 'Talisuna, Ambrose', 'Rajatonirina, Soatiana', 'Fall, Ibrahima Socé']",BMC Public Health,,,False
0113b9a8d82039e8474e887038d643853b5fdfeb,PMC,Revitalization of integrated disease surveillance and response in Sierra Leone post Ebola virus disease outbreak,http://dx.doi.org/10.1186/s12889-019-6636-1,PMC6444503,30940125,CC BY,"BACKGROUND: The Ministry of Health and Sanitation (MOHS) in Sierra Leone partially rolled out the implementation of Integrated Disease Surveillance and Response (IDSR) in 2003. After the Ebola virus disease outbreak in 2014–2015, there was need to strengthen IDSR to ensure prompt detection and response to epidemic-prone diseases. We describe the processes, successes and challenges of revitalizing public health surveillance in a country recovering from a protracted Ebola virus disease outbreak. METHODS: The revitalization process began with adaptation of the revised IDSR guidelines and development of customized guidelines to suit the health care systems in Sierra Leone. Public health experts defined data flow, system operations, case definitions, frequency and channels of reporting and dissemination. Next, phased training of IDSR focal persons in each health facility and the distribution of data collection and reporting tools was done. Monitoring activities included periodic supportive supervision and data quality assessments. Rapid response teams were formed to investigate and respond to disease outbreak alerts in all districts. RESULTS: Submission of reports through the IDSR system began in mid-2015 and by the 35th epidemiologic week, all district health teams were submitting reports. The key performance indicators measuring the functionality of the IDSR system in 2016 and 2017 were achieved (WHO Africa Region target ≥80%); the annual average proportion of timely weekly health facility reports submitted to the next level was 93% in 2016 and 97% in 2017; the proportion of suspected outbreaks and public health events detected through the IDSR system was 96% (n = 87) in 2016 and 100% (n = 85) in 2017. CONCLUSION: With proper planning, phased implementation and adequate investment of resources, it is possible to establish a functional IDSR system in a country recovering from a public health crisis. A functional IDSR system requires well trained workforce, provision of the necessary tools and guidelines, information, communication and technology infrastructure to support data transmission, provision of timely feedback as well as logistical support. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-019-6636-1) contains supplementary material, which is available to authorized users.",2019 Apr 2,"['Njuguna, Charles', 'Jambai, Amara', 'Chimbaru, Alexander', 'Nordstrom, Anders', 'Conteh, Roland', 'Latt, Anderson', 'O-tipo, Shikanga', 'Musoke, Robert', 'Githuku, Jane', 'Yoti, Zablon', 'Yahaya, Ali', 'Talisuna, Ambrose', 'Rajatonirina, Soatiana', 'Fall, Ibrahima Socé']",BMC Public Health,,,True
b07ebfcd149b785998d9a32a9b151e83e9f46c67,PMC,Combination of clinical symptoms and blood biomarkers can improve discrimination between bacterial or viral community-acquired pneumonia in children,http://dx.doi.org/10.1186/s12890-019-0835-5,PMC6444754,30940126,CC BY,"BACKGROUND: Differentiating bacterial from viral pneumonia is important for guiding targeted management and judicious use of antibiotics. We assessed if clinical characteristics and blood inflammatory biomarkers could be used to distinguish bacterial from viral pneumonia. METHODS: Western Australian children (≤17 years) hospitalized with radiologically-confirmed community-acquired pneumonia were recruited and clinical symptoms and management data were collected. C-reactive protein (CRP), white cell counts (WCC) and absolute neutrophil counts (ANC) were measured as part of routine care. Clinical characteristics and biomarker levels were compared between cases with definite bacterial pneumonia (clinical empyema and/or bacteria detected in blood or pleural fluid), presumed viral pneumonia (presence of ≥1 virus in nasopharyngeal swab without criteria for definite bacterial pneumonia), and other pneumonia cases (pneumonia in the absence of criteria for either definite bacterial or presumed viral pneumonia). The area-under-curve (AUC) of the receiver operating characteristic (ROC) curve for varying biomarker levels were used to characterise their utility for discriminating definite bacterial from presumed viral pneumonia. For biomarkers with AUC > 0.8 (fair discriminator), Youden index was measured to determine the optimal cut-off threshold, and sensitivity, specificity, predictive values (positive and negative) were calculated. We investigated whether better discrimination could be achieved by combining biomarker values with the presence/absence of symptoms. RESULTS: From May 2015 to October 2017, 230 pneumonia cases were enrolled: 30 with definite bacterial pneumonia, 118 with presumed viral pneumonia and 82 other pneumonia cases. Differences in clinical signs and symptoms across the groups were noted; more definite bacterial pneumonia cases required intravenous fluid and oxygen supplementation than presumed viral or other pneumonia cases. CRP, WCC and ANC were substantially higher in definite bacterial cases. For a CRP threshold of 72 mg/L, the AUC of ROC was 0.82 for discriminating definite bacterial pneumonia from presumed viral pneumonia. Combining the CRP with either the presence of fever (≥38(ο)C) or the absence of rhinorrhea improved the discrimination. CONCLUSIONS: Combining elevated CRP with the presence or absence of clinical signs/ symptoms differentiates definite bacterial from presumed viral pneumonia better than CRP alone. Further studies are required to explore combination of biomarkers and symptoms for use as definitive diagnostic tool. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12890-019-0835-5) contains supplementary material, which is available to authorized users.",2019 Apr 2,"['Bhuiyan, Mejbah U.', 'Blyth, Christopher C.', 'West, Rachel', 'Lang, Jurissa', 'Rahman, Tasmina', 'Granland, Caitlyn', 'de Gier, Camilla', 'Borland, Meredith L.', 'Thornton, Ruth B.', 'Kirkham, Lea-Ann S.', 'Martin, Andrew', 'Richmond, Peter C.', 'Smith, David W.', 'Jaffe, Adam', 'Snelling, Thomas L.']",BMC Pulm Med,,,True
ccdad2ec94a4e7dfd973faea6ce2fb7854b6bde8,PMC,Acute Flaccid Myelitis: Something Old and Something New,http://dx.doi.org/10.1128/mBio.00521-19,PMC6445942,30940708,CC BY,"Since 2014, acute flaccid myelitis (AFM), a long-recognized condition associated with polioviruses, nonpolio enteroviruses, and various other viral and nonviral causes, has been reemerging globally in epidemic form. This unanticipated reemergence is ironic, given that polioviruses, once the major causes of AFM, are now at the very threshold of global eradication and cannot therefore explain any aspect of AFM reemergence. Instead, the new AFM epidemic has been temporally associated with reemergences of nonpolio enteroviruses such as EV-D68, until recently thought to be an obscure virus of extremely low endemicity. This perspective reviews the enigmatic epidemiologic, virologic, and diagnostic aspects of epidemic AFM reemergence; examines current options for clinical management; discusses future research needs; and suggests that the AFM epidemic offers important clues to mechanisms of viral disease emergence.",2019 Apr 2,"['Morens, David M.', 'Folkers, Gregory K.', 'Fauci, Anthony S.']",mBio,,,True
79d2ee55b54d57041ab6d9a3ecac33bc98d11ff5,PMC,Genes involved in mitochondrial biogenesis and function may not show synchronised responses to mitochondria in shell gland of laying chickens under infectious bronchitis virus challenge,http://dx.doi.org/10.1186/s12860-019-0190-7,PMC6446503,31041887,CC BY,"BACKGROUND: Egg formation takes place in the oviduct of laying hens over a 24 h period. Infectious bronchitis virus (IBV) causes pathological lesions in the chicken oviduct. In the current study, mitochondrial counts were determined in three different segments of the oviduct during egg formation in laying chickens challenged with IBV T strain. Nuclear DNA encoded genes that are involved in mitochondrial biogenesis, fission and function were studied in the shell gland of the oviduct undergoing virus multiplication. RESULTS: In the shell gland, the mitochondrial count was significantly lower (P < 0.05) in the challenged group, compared with the control group. However, it did not vary in response to IBV challenge in the isthmus and magnum regions of the oviduct. The gene succinate dehydrogenase complex, subunit A, flavoprotein variant (SDHA) was down-regulated in the shell gland by IBV challenge (P < 0.05), while other genes being studied did not show responses to the challenge (P > 0.05). Differential expression of the genes was observed at different time-points of egg-shell formation. The expression levels of citrate synthase (CS), cytochrome C, somatic (CYC, S) and sodium-potassium adenosine triphosphatase (Na(+)-K(+)ATPase) genes were significantly higher, while those of SDHA and dynamin related protein 1 (Drp1) genes were significantly lower, at 15 h compared with 5 h following oviposition of the previous egg. The expression level of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) did not show significant change at different time-points. CONCLUSIONS: It was concluded that IBV T strain infection in laying hens reduced mitochondrial counts only in the shell gland region of the oviduct. The genes involved in mitochondrial biogenesis or function may not show synchronised responses to that of mitochondria in the shell gland of chickens under T strain of IBV challenge.",2019 Apr 1,"['Khan, Samiullah', 'Roberts, Juliet', 'Wu, Shu-Biao']",BMC Mol Cell Biol,,,True
a52566f6d96ec5a9a371582766a992a4ac38bd64,PMC,"Using GPS collars to investigate the frequency and behavioural outcomes of intraspecific interactions among carnivores: A case study of male cheetahs in the Maasai Mara, Kenya",http://dx.doi.org/10.1371/journal.pone.0213910,PMC6447186,30943236,CC BY,"Intraspecific interactions between individuals or groups of individuals of the same species are an important component of population dynamics. Interactions can be static, such as spatial overlap, or dynamic based on the interactions of movements, and can be mediated through communication, such as the deployment of scent marks. Interactions and their behavioural outcomes can be difficult to determine, especially for species that live at low densities. With the use of GPS collars we quantify both static and dynamic interactions between male cheetahs (Acinonyx jubatus) and the behavioural outcomes. The 99% home-ranges of males overlapped significantly while there was little overlap of the 50% home-ranges. Despite this overlap, male cheetahs rarely came into close proximity of one another, possibly because presence was communicated through frequent visits to marking posts. The minimum distance between individuals in a dyad ranged from 89m to 196m but the average proximity between individuals ranged from 17,145 ± 6,865m to 26,367 ± 11,288m. Possible interactions took place more frequently at night than by day and occurred mostly in the 50% home-range of one individual of a dyad or where cores of both individuals overlapped. After a possible encounter male cheetahs stayed in close proximity to each other for up to 6 hours, which could be the result of a territory defence strategy or the presence of a receptive female. We believe that one of the encounters between a singleton and a 5-male coalition resulted in the death of the singleton. Our results give new insights into cheetah interactions, which could help our understanding of ecological processes such as disease transmission.",2019 Apr 3,"['Broekhuis, Femke', 'Madsen, Emily K.', 'Keiwua, Kosiom', 'Macdonald, David W.']",PLoS One,,,True
c2f36f9f3eac1b4ba6051acc67dc8f8e8ca169cd,PMC,"Using GPS collars to investigate the frequency and behavioural outcomes of intraspecific interactions among carnivores: A case study of male cheetahs in the Maasai Mara, Kenya",http://dx.doi.org/10.1371/journal.pone.0213910,PMC6447186,30943236,CC BY,"Intraspecific interactions between individuals or groups of individuals of the same species are an important component of population dynamics. Interactions can be static, such as spatial overlap, or dynamic based on the interactions of movements, and can be mediated through communication, such as the deployment of scent marks. Interactions and their behavioural outcomes can be difficult to determine, especially for species that live at low densities. With the use of GPS collars we quantify both static and dynamic interactions between male cheetahs (Acinonyx jubatus) and the behavioural outcomes. The 99% home-ranges of males overlapped significantly while there was little overlap of the 50% home-ranges. Despite this overlap, male cheetahs rarely came into close proximity of one another, possibly because presence was communicated through frequent visits to marking posts. The minimum distance between individuals in a dyad ranged from 89m to 196m but the average proximity between individuals ranged from 17,145 ± 6,865m to 26,367 ± 11,288m. Possible interactions took place more frequently at night than by day and occurred mostly in the 50% home-range of one individual of a dyad or where cores of both individuals overlapped. After a possible encounter male cheetahs stayed in close proximity to each other for up to 6 hours, which could be the result of a territory defence strategy or the presence of a receptive female. We believe that one of the encounters between a singleton and a 5-male coalition resulted in the death of the singleton. Our results give new insights into cheetah interactions, which could help our understanding of ecological processes such as disease transmission.",2019 Apr 3,"['Broekhuis, Femke', 'Madsen, Emily K.', 'Keiwua, Kosiom', 'Macdonald, David W.']",PLoS One,,,False
25a3215cab1bb95d05f54bed2626352254779c8e,PMC,High titer MVA and influenza A virus production using a hybrid fed-batch/perfusion strategy with an ATF system,http://dx.doi.org/10.1007/s00253-019-09694-2,PMC6447503,30796494,CC BY,"A cultivation strategy to increase the productivity of Modified Vaccinia Ankara (MVA) virus in high-cell density processes is presented. Based on an approach developed in shake flask cultures, this strategy was established in benchtop bioreactors, comprising the growth of suspension AGE1.CR.pIX cells to high cell densities in a chemically defined medium before infection with the MVA-CR19 virus strain. First, a perfusion regime was established to optimize the cell growth phase. Second, a fed-batch regime was chosen for the initial infection phase to facilitate virus uptake and cell-to-cell spreading. Afterwards, a switch to perfusion enabled the continuous supply of nutrients for the late stages of virus propagation. With maximum infectious titers of 1.0 × 10(10) IU/mL, this hybrid fed-batch/perfusion strategy increased product titers by almost one order of magnitude compared to conventional batch cultivations. Finally, this strategy was also applied to the production of influenza A/PR/8/34 (H1N1) virus considered for manufacturing of inactivated vaccines. Using the same culture system, a total number of 3.8 × 10(10) virions/mL was achieved. Overall, comparable or even higher cell-specific virus yields and volumetric productivities were obtained using the same cultivation systems as for the conventional batch cultivations. In addition, most viral particles were found in the culture supernatant, which can simplify further downstream operations, in particular for MVA viruses. Considering the current availability of well-described perfusion/cell retention technologies, the present strategy may contribute to the development of new approaches for viral vaccine production. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-019-09694-2) contains supplementary material, which is available to authorized users.",2019 Feb 23,"['Vázquez-Ramírez, Daniel', 'Jordan, Ingo', 'Sandig, Volker', 'Genzel, Yvonne', 'Reichl, Udo']",Appl Microbiol Biotechnol,,,False
63fb289aa51f77907321626b838ccae5e0939dc1,PMC,High titer MVA and influenza A virus production using a hybrid fed-batch/perfusion strategy with an ATF system,http://dx.doi.org/10.1007/s00253-019-09694-2,PMC6447503,30796494,CC BY,"A cultivation strategy to increase the productivity of Modified Vaccinia Ankara (MVA) virus in high-cell density processes is presented. Based on an approach developed in shake flask cultures, this strategy was established in benchtop bioreactors, comprising the growth of suspension AGE1.CR.pIX cells to high cell densities in a chemically defined medium before infection with the MVA-CR19 virus strain. First, a perfusion regime was established to optimize the cell growth phase. Second, a fed-batch regime was chosen for the initial infection phase to facilitate virus uptake and cell-to-cell spreading. Afterwards, a switch to perfusion enabled the continuous supply of nutrients for the late stages of virus propagation. With maximum infectious titers of 1.0 × 10(10) IU/mL, this hybrid fed-batch/perfusion strategy increased product titers by almost one order of magnitude compared to conventional batch cultivations. Finally, this strategy was also applied to the production of influenza A/PR/8/34 (H1N1) virus considered for manufacturing of inactivated vaccines. Using the same culture system, a total number of 3.8 × 10(10) virions/mL was achieved. Overall, comparable or even higher cell-specific virus yields and volumetric productivities were obtained using the same cultivation systems as for the conventional batch cultivations. In addition, most viral particles were found in the culture supernatant, which can simplify further downstream operations, in particular for MVA viruses. Considering the current availability of well-described perfusion/cell retention technologies, the present strategy may contribute to the development of new approaches for viral vaccine production. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-019-09694-2) contains supplementary material, which is available to authorized users.",2019 Feb 23,"['Vázquez-Ramírez, Daniel', 'Jordan, Ingo', 'Sandig, Volker', 'Genzel, Yvonne', 'Reichl, Udo']",Appl Microbiol Biotechnol,,,True
c03edc5c954ae36334ee52e5b60ef611d075d1ac,PMC,Infectious Disease Threats in the Twenty-First Century: Strengthening the Global Response,http://dx.doi.org/10.3389/fimmu.2019.00549,PMC6447676,30984169,CC BY,"The world has developed an elaborate global health system as a bulwark against known and unknown infectious disease threats. The system consists of various formal and informal networks of organizations that serve different stakeholders; have varying goals, modalities, resources, and accountability; operate at different regional levels (i.e., local, national, regional, or global); and cut across the public, private-for-profit, and private-not-for-profit sectors. The evolving global health system has done much to protect and promote human health. However, the world continues to be confronted by longstanding, emerging, and reemerging infectious disease threats. These threats differ widely in terms of severity and probability. They also have varying consequences for morbidity and mortality, as well as for a complex set of social and economic outcomes. To various degrees, they are also amenable to alternative responses, ranging from clean water provision to regulation to biomedical countermeasures. Whether the global health system as currently constituted can provide effective protection against a dynamic array of infectious disease threats has been called into question by recent outbreaks of Ebola, Zika, dengue, Middle East respiratory syndrome, severe acute respiratory syndrome, and influenza and by the looming threat of rising antimicrobial resistance. The concern is magnified by rapid population growth in areas with weak health systems, urbanization, globalization, climate change, civil conflict, and the changing nature of pathogen transmission between human and animal populations. There is also potential for human-originated outbreaks emanating from laboratory accidents or intentional biological attacks. This paper discusses these issues, along with the need for a (possibly self-standing) multi-disciplinary Global Technical Council on Infectious Disease Threats to address emerging global challenges with regard to infectious disease and associated social and economic risks. This Council would strengthen the global health system by improving collaboration and coordination across organizations (e.g., the WHO, Gavi, CEPI, national centers for disease control, pharmaceutical manufacturers, etc.); filling in knowledge gaps with respect to (for example) infectious disease surveillance, research and development needs, financing models, supply chain logistics, and the social and economic impacts of potential threats; and making high-level, evidence-based recommendations for managing global risks associated with infectious disease.",2019 Mar 28,"['Bloom, David E.', 'Cadarette, Daniel']",Front Immunol,,,True
e4ea49d8e5168e27636315e248bad09766c31a2d,PMC,"Recent Aspects on the Pathogenesis Mechanism, Animal Models and Novel Therapeutic Interventions for Middle East Respiratory Syndrome Coronavirus Infections",http://dx.doi.org/10.3389/fmicb.2019.00569,PMC6448012,30984127,CC BY,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging zoonotic virus considered as one of the major public threat with a total number of 2 298 laboratory-confirmed cases and 811 associated deaths reported by World Health Organization as of January 2019. The transmission of the virus was expected to be from the camels found in Middle Eastern countries via the animal and human interaction. The genome structure provided information about the pathogenicity and associated virulent factors present in the virus. Recent studies suggested that there were limited insight available on the development of novel therapeutic strategies to induce immunity against the virus. The severities of MERS-CoV infection highlight the necessity of effective approaches for the development of various therapeutic remedies. Thus, the present review comprehensively and critically illustrates the recent aspects on the epidemiology of the virus, the structural and functional features of the viral genome, viral entry and transmission, major mechanisms of pathogenesis and associated virulent factors, current animal models, detection methods and novel strategies for the development of vaccines against MERS-CoV. The review further illustrates the molecular and computational virtual screening platforms which provide insights for the identification of putative drug targets and novel lead molecules toward the development of therapeutic remedies.",2019 Mar 26,"['Skariyachan, Sinosh', 'Challapilli, Sneha Basavaraj', 'Packirisamy, Swathi', 'Kumargowda, Supreetha Toplar', 'Sridhar, Vaishnavi Sneha']",Front Microbiol,,,True
5794890e355a8abbec51b46d767b6ee67edcd274,PMC,Zika Virus Infection Disrupts Astrocytic Proteins Involved in Synapse Control and Axon Guidance,http://dx.doi.org/10.3389/fmicb.2019.00596,PMC6448030,30984137,CC BY,"The first human Zika virus (ZIKV) outbreak was reported in Micronesia in 2007, followed by one in Brazil in 2015. Recent studies have reported cases in Europe, Oceania and Latin America. In 2016, ZIKV transmission was also reported in the US and the World Health Organization declared it a Public Health Emergency of International Concern. Because various neurological conditions are associated with ZIKV, such as microcephaly, Guillain-Barré syndrome, and other disorders of both the central and peripheral nervous systems, including encephalopathy, (meningo)encephalitis and myelitis, and because of the lack of reliable patient diagnosis, numerous ongoing studies seek to understand molecular mechanisms underlying ZIKV pathogenesis. Astrocytes are one of the most abundant cells in the CNS. They control axonal guidance, synaptic signaling, neurotransmitter trafficking and maintenance of neurons, and are targeted by ZIKV. In this study, we used a newly developed multiplexed aptamer-based technique (SOMAScan) to examine > 1300 human astrocyte cell proteins. We identified almost 300 astrocyte proteins significantly dysregulated by ZIKV infection that span diverse functions and signaling pathways, including protein translation, synaptic control, cell migration and differentiation.",2019 Mar 26,"['Sher, Affan A.', 'Glover, Kathleen K. M.', 'Coombs, Kevin M.']",Front Microbiol,,,True
0dc510092156faececbbdf95cb57ba32ea03da4d,PMC,Zika Virus Infection Disrupts Astrocytic Proteins Involved in Synapse Control and Axon Guidance,http://dx.doi.org/10.3389/fmicb.2019.00596,PMC6448030,30984137,CC BY,"The first human Zika virus (ZIKV) outbreak was reported in Micronesia in 2007, followed by one in Brazil in 2015. Recent studies have reported cases in Europe, Oceania and Latin America. In 2016, ZIKV transmission was also reported in the US and the World Health Organization declared it a Public Health Emergency of International Concern. Because various neurological conditions are associated with ZIKV, such as microcephaly, Guillain-Barré syndrome, and other disorders of both the central and peripheral nervous systems, including encephalopathy, (meningo)encephalitis and myelitis, and because of the lack of reliable patient diagnosis, numerous ongoing studies seek to understand molecular mechanisms underlying ZIKV pathogenesis. Astrocytes are one of the most abundant cells in the CNS. They control axonal guidance, synaptic signaling, neurotransmitter trafficking and maintenance of neurons, and are targeted by ZIKV. In this study, we used a newly developed multiplexed aptamer-based technique (SOMAScan) to examine > 1300 human astrocyte cell proteins. We identified almost 300 astrocyte proteins significantly dysregulated by ZIKV infection that span diverse functions and signaling pathways, including protein translation, synaptic control, cell migration and differentiation.",2019 Mar 26,"['Sher, Affan A.', 'Glover, Kathleen K. M.', 'Coombs, Kevin M.']",Front Microbiol,,,False
39b3c93ff2d69d022e80c98663a675d52aae4ea4,PMC,Zika Virus Infection Disrupts Astrocytic Proteins Involved in Synapse Control and Axon Guidance,http://dx.doi.org/10.3389/fmicb.2019.00596,PMC6448030,30984137,CC BY,"The first human Zika virus (ZIKV) outbreak was reported in Micronesia in 2007, followed by one in Brazil in 2015. Recent studies have reported cases in Europe, Oceania and Latin America. In 2016, ZIKV transmission was also reported in the US and the World Health Organization declared it a Public Health Emergency of International Concern. Because various neurological conditions are associated with ZIKV, such as microcephaly, Guillain-Barré syndrome, and other disorders of both the central and peripheral nervous systems, including encephalopathy, (meningo)encephalitis and myelitis, and because of the lack of reliable patient diagnosis, numerous ongoing studies seek to understand molecular mechanisms underlying ZIKV pathogenesis. Astrocytes are one of the most abundant cells in the CNS. They control axonal guidance, synaptic signaling, neurotransmitter trafficking and maintenance of neurons, and are targeted by ZIKV. In this study, we used a newly developed multiplexed aptamer-based technique (SOMAScan) to examine > 1300 human astrocyte cell proteins. We identified almost 300 astrocyte proteins significantly dysregulated by ZIKV infection that span diverse functions and signaling pathways, including protein translation, synaptic control, cell migration and differentiation.",2019 Mar 26,"['Sher, Affan A.', 'Glover, Kathleen K. M.', 'Coombs, Kevin M.']",Front Microbiol,,,False
6b25e6dd5339756b75ff7633e55525fd49366b0e,PMC,Zika Virus Infection Disrupts Astrocytic Proteins Involved in Synapse Control and Axon Guidance,http://dx.doi.org/10.3389/fmicb.2019.00596,PMC6448030,30984137,CC BY,"The first human Zika virus (ZIKV) outbreak was reported in Micronesia in 2007, followed by one in Brazil in 2015. Recent studies have reported cases in Europe, Oceania and Latin America. In 2016, ZIKV transmission was also reported in the US and the World Health Organization declared it a Public Health Emergency of International Concern. Because various neurological conditions are associated with ZIKV, such as microcephaly, Guillain-Barré syndrome, and other disorders of both the central and peripheral nervous systems, including encephalopathy, (meningo)encephalitis and myelitis, and because of the lack of reliable patient diagnosis, numerous ongoing studies seek to understand molecular mechanisms underlying ZIKV pathogenesis. Astrocytes are one of the most abundant cells in the CNS. They control axonal guidance, synaptic signaling, neurotransmitter trafficking and maintenance of neurons, and are targeted by ZIKV. In this study, we used a newly developed multiplexed aptamer-based technique (SOMAScan) to examine > 1300 human astrocyte cell proteins. We identified almost 300 astrocyte proteins significantly dysregulated by ZIKV infection that span diverse functions and signaling pathways, including protein translation, synaptic control, cell migration and differentiation.",2019 Mar 26,"['Sher, Affan A.', 'Glover, Kathleen K. M.', 'Coombs, Kevin M.']",Front Microbiol,,,False
c9f6aba70979afa9fe1c10df0bce3909b26bb678,PMC,Anti-H7N9 avian influenza A virus activity of interferon in pseudostratified human airway epithelium cell cultures,http://dx.doi.org/10.1186/s12985-019-1146-4,PMC6448296,30944006,CC BY,"BACKGROUND: Since H7N9 influenza A virus (H7N9) was first reported in 2013, five waves of outbreaks have occurred, posing a huge threat to human health. In preparation for a potential H7N9 epidemic, it is essential to evaluate the efficacy of anti-H7N9 drugs with an appropriate model. METHODS: Well-differentiated pseudostratified human airway epithelium (HAE) cells were grown at the air–liquid interface, and the H7N9 cell tropism and cytopathic effect were detected by immunostaining and hematoxylin-eosin (HE) staining. The H7N9 replication kinetics and anti-H7N9 effect of recombinant human α2b (rhIFN-α2b) and rhIFN-λ1 were compared with different cell lines. The H7N9 viral load and interferon-stimulated gene (ISG) expression were quantified by real-time PCR assays. RESULTS: H7N9 could infect both ciliated and non-ciliated cells within the three-dimensional (3D) HAE cell culture, which reduced the number of cilia and damaged the airways. The H7N9 replication kinetics differed between traditional cells and 3D HAE cells. Interferon had antiviral activity against H7N9 and alleviated epithelial cell lesions; the antiviral activity of rhIFN-α2b was slightly better than that of rhIFN-λ1. In normal cells, rhIFN-α2b induced a greater amount of ISG expression (MX1, OAS1, IFITM3, and ISG15) compared with rhIFN-λ1, but in 3D HAE cells, this trend was reversed. CONCLUSIONS: Both rhIFN-α2b and rhIFN-λ1 had antiviral activity against H7N9, and this protection was related to the induction of ISGs. The 3D cell culture model is suitable for evaluating interferon antiviral activity because it can demonstrate realistic in vivo-like effects.",2019 Apr 3,"['Chen, Ai-jun', 'Dong, Jie', 'Yuan, Xin-hui', 'Bo, Hong', 'Li, Shu-zhen', 'Wang, Chao', 'Duan, Zhao-jun', 'Zheng, Li-shu']",Virol J,,,True
c5f1d681eb128c9c044a7f5ced6e0e943b201e93,PMC,A new Schiff base coordinated copper(II) compound induces apoptosis and inhibits tumor growth in gastric cancer,http://dx.doi.org/10.1186/s12935-019-0801-6,PMC6448317,30988662,CC BY,"BACKGROUND: Gastric cancer, as a multifactorial disorders, shows cytological and architectural heterogeneity compared to other gastrointestinal cancers, making it therapeutically challenging. Cisplatin is generally used in clinic for gastric cancer treatment but with toxic side effects and develops resistance. Anti-tumor properties of copper and its coordinated compounds have been explored intensively in recent years. METHODS: In this study, we synthesized a novel Schiff base copper coordinated compound (SBCCC) and examined its antitumor effects in two gastric cancer cell lines SGC-7901 and BGC-823 as well as a mouse model of gastric cancer. RESULTS: The results show that SBCCC can significantly inhibit the proliferation of gastric cancer cells in a dose- and time-dependent manner. The IC50 of SBCCC in SGC-7901 and BGC-823 cells is 1 μM, which is much less than cisplatin’s IC50. SBCCC induces apoptosis and causes cell cycle arrest at the G1 phase. SBCCC induces apoptosis via multiple pathways including inhibition of NF-κB, ROS production and autophagy. CONCLUSIONS: The synthesized SBCCC induced cancer cell death via inhibition of NF-κB, ROS production and autophagy. The multiple cell-killing mechanisms were important to overcome therapeutic failure because of multidrug-resistance of cancer cells. SBCCC, with a lower IC50 compared to cisplatin, could render it the potential to overcome the side-effect for clinical application.",2019 Apr 3,"['Xia, Yan', 'Liu, Xingkai', 'Zhang, Luping', 'Zhang, Jinzhu', 'Li, Chaoying', 'Zhang, Nan', 'Xu, Hong', 'Li, Yan']",Cancer Cell Int,,,True
066619641442d9c3f6a547301849bef0b8b12f2f,PMC,Perspectives of Australian policy-makers on the potential benefits and risks of technologically enhanced communicable disease surveillance – a modified Delphi survey,http://dx.doi.org/10.1186/s12961-019-0440-3,PMC6449976,30947721,CC BY,"BACKGROUND: Event-based social media monitoring and pathogen whole genome sequencing (WGS) will enhance communicable disease surveillance research and systems. If linked electronically and scanned systematically, the information provided by these technologies could be mined to uncover new epidemiological patterns and associations much faster than traditional public health approaches. The benefits of earlier outbreak detection are significant, but implementation could be opposed in the absence of a social licence or if ethical and legal concerns are not addressed. METHODS: A three-phase mixed-method Delphi survey with Australian policy-makers, health practitioners and lawyers (n = 44) was conducted to explore areas of consensus and disagreement over (1) key policy and practical issues raised by the introduction of novel communicable disease surveillance programmes; and (2) the most significant and likely risks from using social media content and WGS technologies in epidemiological research and outbreak investigations. RESULTS: Panellists agreed that the integration of social media monitoring and WGS technologies into communicable disease surveillance systems raised significant issues, including impacts on personal privacy, medicolegal risks and the potential for unintended consequences. Notably, their concerns focused on how these technologies should be used, rather than how the data was collected. Panellists held that social media users should expect their posts to be monitored in the interests of public health, but using those platforms to contact identified individuals was controversial. The conditions of appropriate use of pathogen WGS in epidemiological research and investigations was also contentious. Key differences amongst participants included the necessity for consent before testing and data-linkage, thresholds for action, and the legal and ethical importance of harms to individuals and commercial entities. The erosion of public trust was seen as the most significant risk from the systematic use of these technologies. CONCLUSIONS: Enhancing communicable disease surveillance with social-media monitoring and pathogen WGS may cause controversy. The challenge is to determine and then codify how these technologies should be used such that the balance between individual risk and community benefit is widely accepted. Participants agreed that clear guidelines for appropriate use that address legal and ethical concerns need to be developed in consultation with relevant experts and the broader Australian public. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12961-019-0440-3) contains supplementary material, which is available to authorized users.",2019 Apr 4,"['Degeling, Chris', 'Johnson, Jane', 'Gilbert, Gwendolyn L.']",Health Res Policy Syst,,,True
889915a03b21c44b0c3d21f13fb8d04a7cdd0f50,PMC,Contribution of Fcγ Receptor-Mediated Immunity to the Pathogenesis Caused by the Human Respiratory Syncytial Virus,http://dx.doi.org/10.3389/fcimb.2019.00075,PMC6450440,30984626,CC BY,"The human Respiratory Syncytial Virus (hRSV) is the leading cause of severe acute lower respiratory tract infections (ALRTIs) in humans at all ages and is the main cause of hospitalization due to pneumonia, asthma, and bronchiolitis in infants. hRSV symptoms mainly develop due to an excessive host immune and inflammatory response in the respiratory tissue. hRSV infection during life is frequent and likely because of non-optimal immunological memory is developed against this virus. Vaccine development against this pathogen has been delayed after the detrimental effects produced in children by vaccination with a formalin-inactivated hRSV preparation (FI-hRSV), which caused enhanced disease upon natural viral infection. Since then, several studies have focused on understanding the mechanisms underlying such disease exacerbation. Along these lines, several studies have suggested that antibodies elicited by immunization with FI-hRSV show low neutralizing capacity and promote the formation of immune complexes containing hRSV (hRSV-ICs), which contribute to hRSV pathogenesis through the engagement of Fc gamma receptors (FcγRs) expressed on the surface of immune cells. Furthermore, a role for FcγRs is supported by studies evaluating the contribution of these molecules to hRSV-induced disease. These studies have shown that FcγRs can modulate viral clearance by the host and the inflammatory response triggered by hRSV infection. In addition, ICs can facilitate viral entry into host cells expressing FcγRs, thus extending hRSV infectivity. In this article, we discuss current knowledge relative to the contribution of hRSV-ICs and FcγRs to the pathogenesis caused by hRSV and their putative role in the exacerbation of the disease caused by this virus after FI-hRSV vaccination. A better understanding FcγRs involvement in the immune response against hRSV will contribute to the development of new prophylactic or therapeutic tools to promote virus clearance with limited inflammatory damage to the airways.",2019 Mar 29,"['Acevedo, Orlando A.', 'Díaz, Fabián E.', 'Beals, Tomas E.', 'Benavente, Felipe M.', 'Soto, Jorge A.', 'Escobar-Vera, Jorge', 'González, Pablo A.', 'Kalergis, Alexis M.']",Front Cell Infect Microbiol,,,True
d18a705998ad871dad46aeabeeed0a20909c10df,PMC,"“Epidemiology and aetiology of influenza-like illness among households in metropolitan Vientiane, Lao PDR”: A prospective, community-based cohort study",http://dx.doi.org/10.1371/journal.pone.0214207,PMC6450629,30951544,CC BY,"Respiratory diseases are a major contributor to morbidity and mortality in many tropical countries, including Lao PDR. However, little has been published regarding viral or bacterial pathogens that can contribute to influenza-like illness (ILI) in a community setting. We report on the results of a community-based surveillance that prospectively monitored the incidence of ILI and its causative pathogens in Vientiane capital in Lao PDR. A cohort of 995 households, including 4885 study participants, were followed-up between May 2015 and May 2016. Nasopharyngeal swabs, throat swabs, and sputum specimens were collected from ILI cases identified through active case-finding. Real-Time PCR was used to test nasopharyngeal swabs for 21 respiratory pathogens, while throat and sputum samples were subjected to bacterial culture. Generalized linear mixed models were used to assess potential risk factors for associations with ILI. In total, 548 episodes of ILI were reported among 476 (9.7%) of the study participants and 330 (33.2%) of the study households. The adjusted estimated incidence of ILI within the study area was 10.7 (95%CI: 9.4–11.9) episodes per 100 person-years. ILI was significantly associated with age group (p<0.001), sex (p<0.001), and number of bedrooms (p = 0.04) in multivariate analysis. In 548 nasopharyngeal swabs, the most commonly detected potential pathogens were Streptococcus pneumoniae (17.0%), Staphylococcus aureus (11.3%), influenza A (11.1%; mostly subtype H3N2), rhinovirus (7.5%), and influenza B (8.0%). Streptococci were isolated from 42 (8.6%) of 536 throat swabs, most (27) of which were Lancefield Group G. Co-infections were observed in 132 (24.1%) of the 548 ILI episodes. Our study generated valuable data on respiratory disease burden and patterns of etiologies associated with community-acquired acute respiratory illness Laos. Establishment of a surveillance strategy in Laos to monitor trends in the epidemiology and burden of acute respiratory infections is required to minimize their impact on human health.",2019 Apr 5,"['Rudge, James W.', 'Inthalaphone, Nui', 'Pavlicek, Rebecca', 'Paboriboune, Phimpha', 'Flaissier, Bruno', 'Monidarin, Chou', 'Steenkeste, Nicolas', 'Davong, Viengmon', 'Vongsouvath, Manivanh', 'Bonath, K. A.', 'Messaoudi, Melinda', 'Saadatian-Elahi, Mitra', 'Newton, Paul', 'Endtz, Hubert', 'Dance, David', 'Paranhos Baccala, Glaucia', 'Sanchez Picot, Valentina']",PLoS One,,,True
208137ab9d47db2caf64bcb88702e580b16375f9,PMC,Inevitable isolation and the change of stress markers in hemodialysis patients during the 2015 MERS-CoV outbreak in Korea,http://dx.doi.org/10.1038/s41598-019-41964-x,PMC6450937,30952879,CC BY,"During the outbreak of Middle East respiratory syndrome coronavirus(MERS-CoV) in 2015, one hemodialysis patient was infected with MERS-CoV, and the remaining hemodialysis(HD) patients (n = 83) and medical staff (n = 12) had to undergo dialysis treatment in an isolated environment. This study was performed to investigate the effects of stress caused by dialysis treatment under isolation. Plasma samples from the HD patients and medical staff were collected at the time of isolation(M0), the following month(M1), and three months after isolation(M3). Parameters for stress included circulating cell-free genomic DNA(ccf-gDNA), circulating cell-free mitochondria DNA(ccf-mtDNA), and pentraxin-3(PTX-3). Decreased values of Hct, kt/v and ca x p were recovered after the end of two weeks of isolation. The levels of ccf-gDNA and ccf-mtDNA were the highest at M0 and decreased gradually in both HD patients and the medical staff. The normalization of ccf-gDNA and ccf-mtDNA was significantly delayed in HD patients compared with the response in the medical staff. PTX-3 increased only in HD patients and was highest at M0, and it then gradually decreased. Medical isolation and subnormal quality of care during the MERS outbreak caused extreme stress in HD patients. Plasma cell-free DNA and PTX-3 seems to be good indicators of stress and quality of care in HD patients.",2019 Apr 5,"['Kim, Yang Gyun', 'Moon, Haena', 'Kim, Se-Yun', 'Lee, Yu-Ho', 'Jeong, Da-Wun', 'Kim, Kipyo', 'Moon, Ju Young', 'Lee, Young-Ki', 'Cho, Ajin', 'Lee, Hong-Seock', 'Park, Hayne Cho', 'Lee, Sang-Ho']",Sci Rep,,,False
418826a231c08bed06a47bd7d0b96dcdf66bd3e6,PMC,Inevitable isolation and the change of stress markers in hemodialysis patients during the 2015 MERS-CoV outbreak in Korea,http://dx.doi.org/10.1038/s41598-019-41964-x,PMC6450937,30952879,CC BY,"During the outbreak of Middle East respiratory syndrome coronavirus(MERS-CoV) in 2015, one hemodialysis patient was infected with MERS-CoV, and the remaining hemodialysis(HD) patients (n = 83) and medical staff (n = 12) had to undergo dialysis treatment in an isolated environment. This study was performed to investigate the effects of stress caused by dialysis treatment under isolation. Plasma samples from the HD patients and medical staff were collected at the time of isolation(M0), the following month(M1), and three months after isolation(M3). Parameters for stress included circulating cell-free genomic DNA(ccf-gDNA), circulating cell-free mitochondria DNA(ccf-mtDNA), and pentraxin-3(PTX-3). Decreased values of Hct, kt/v and ca x p were recovered after the end of two weeks of isolation. The levels of ccf-gDNA and ccf-mtDNA were the highest at M0 and decreased gradually in both HD patients and the medical staff. The normalization of ccf-gDNA and ccf-mtDNA was significantly delayed in HD patients compared with the response in the medical staff. PTX-3 increased only in HD patients and was highest at M0, and it then gradually decreased. Medical isolation and subnormal quality of care during the MERS outbreak caused extreme stress in HD patients. Plasma cell-free DNA and PTX-3 seems to be good indicators of stress and quality of care in HD patients.",2019 Apr 5,"['Kim, Yang Gyun', 'Moon, Haena', 'Kim, Se-Yun', 'Lee, Yu-Ho', 'Jeong, Da-Wun', 'Kim, Kipyo', 'Moon, Ju Young', 'Lee, Young-Ki', 'Cho, Ajin', 'Lee, Hong-Seock', 'Park, Hayne Cho', 'Lee, Sang-Ho']",Sci Rep,,,True
0c3ceccabeff0296e424a649fe5931a1671f9905,PMC,A host gene expression approach for identifying triggers of asthma exacerbations,http://dx.doi.org/10.1371/journal.pone.0214871,PMC6453459,30958855,CC0,"RATIONALE: Asthma exacerbations often occur due to infectious triggers, but determining whether infection is present and whether it is bacterial or viral remains clinically challenging. A diagnostic strategy that clarifies these uncertainties could enable personalized asthma treatment and mitigate antibiotic overuse. OBJECTIVES: To explore the performance of validated peripheral blood gene expression signatures in discriminating bacterial, viral, and noninfectious triggers in subjects with asthma exacerbations. METHODS: Subjects with suspected asthma exacerbations of various etiologies were retrospectively selected for peripheral blood gene expression analysis from a pool of subjects previously enrolled in emergency departments with acute respiratory illness. RT-PCR quantified 87 gene targets, selected from microarray-based studies, followed by logistic regression modeling to define bacterial, viral, or noninfectious class. The model-predicted class was compared to clinical adjudication and procalcitonin. RESULTS: Of 46 subjects enrolled, 7 were clinically adjudicated as bacterial, 18 as viral, and 21 as noninfectious. Model prediction was congruent with clinical adjudication in 15/18 viral and 13/21 noninfectious cases, but only 1/7 bacterial cases. None of the adjudicated bacterial cases had confirmatory microbiology; the precise etiology in this group was uncertain. Procalcitonin classified only one subject in the cohort as bacterial. 47.8% of subjects received antibiotics. CONCLUSIONS: Our model classified asthma exacerbations by the underlying bacterial, viral, and noninfectious host response. Compared to clinical adjudication, the majority of discordances occurred in the bacterial group, due to either imperfect adjudication or model misclassification. Bacterial infection was identified infrequently by all classification schemes, but nearly half of subjects were prescribed antibiotics. A gene expression-based approach may offer useful diagnostic information in this population and guide appropriate antibiotic use.",2019 Apr 8,"['Lydon, Emily C.', 'Bullard, Charles', 'Aydin, Mert', 'Better, Olga M.', 'Mazur, Anna', 'Nicholson, Bradly P.', 'Ko, Emily R.', 'McClain, Micah T.', 'Ginsburg, Geoffrey S.', 'Woods, Chris W.', 'Burke, Thomas W.', 'Henao, Ricardo', 'Tsalik, Ephraim L.']",PLoS One,,,True
46c3d464e9fb7f7ccffeae216e82fe33465074bd,PMC,Bumped kinase inhibitor 1369 is effective against Cystoisospora suis in vivo and in vitro,http://dx.doi.org/10.1016/j.ijpddr.2019.03.004,PMC6453670,30959327,CC BY,"Cystoisosporosis is a leading diarrheal disease in suckling piglets. With the confirmation of resistance against the only available drug toltrazuril, there is a substantial need for novel therapeutics to combat the infection and its negative effects on animal health. In closely related apicomplexan species, bumped kinase inhibitors (BKIs) targeting calcium-dependent protein kinase 1 (CDPK1) were shown to be effective in inhibiting host-cell invasion and parasite growth. Therefore, the gene coding for Cystoisospora suis CDPK1 (CsCDPK1) was identified and cloned to investigate activity and thermal stabilization of the recombinant CsCDPK1 enzyme by BKI 1369. In this comprehensive study, the efficacy, safety and pharmacokinetics of BKI 1369 in piglets experimentally infected with Cystoisospora suis (toltrazuril-sensitive, Wien-I and toltrazuril-resistant, Holland-I strains) were determined in vivo and in vitro using an established animal infection model and cell culture, respectively. BKI 1369 inhibited merozoite proliferation in intestinal porcine epithelial cells-1 (IPEC-1) by at least 50% at a concentration of 40 nM, and proliferation was almost completely inhibited (>95%) at 200 nM. Nonetheless, exposure of infected cultures to 200 nM BKI 1369 for five days did not induce structural alterations in surviving merozoites as confirmed by transmission electron microscopy. Five-day treatment with BKI 1369 (10 mg/kg BW twice a day) effectively suppressed oocyst excretion and diarrhea and improved body weight gains in treated piglets without obvious side effects for both toltrazuril-sensitive, Wien-I and resistant, Holland-I C. suis strains. The plasma concentration of BKI 1369 in piglets increased to 11.7 μM during treatment, suggesting constant drug accumulation and exposure of parasites to the drug. Therefore, oral applications of BKI 1369 could potentially be a therapeutic alternative against porcine cystoisosporosis. For use in pigs, future studies on BKI 1369 should be directed towards ease of drug handling and minimizing treatment frequencies.",2019 Apr 2,"['Shrestha, Aruna', 'Ojo, Kayode K.', 'Koston, Florian', 'Ruttkowski, Bärbel', 'Vidadala, Rama S.R.', 'Dorr, Carlie S.', 'Navaluna, Edelmar D.', 'Whitman, Grant R.', 'Barrett, Kayleigh F.', 'Barrett, Lynn K.', 'Hulverson, Matthew A.', 'Choi, Ryan', 'Michaels, Samantha A.', 'Maly, Dustin J.', 'Hemphill, Andrew', 'Van Voorhis, Wesley C.', 'Joachim, Anja']",Int J Parasitol Drugs Drug Resist,,,False
842863c4f79b4d13ef260ef46b9882e8afe2b8ee,PMC,A novel method for the capture-based purification of whole viral native RNA genomes,http://dx.doi.org/10.1186/s13568-019-0772-y,PMC6453989,30963294,CC BY,"Current technologies for targeted characterization and manipulation of viral RNA primarily involve amplification or ultracentrifugation with isopycnic gradients of viral particles to decrease host RNA background. The former strategy is non-compatible for characterizing properties innate to RNA strands such as secondary structure, RNA–RNA interactions, and also for nanopore direct RNA sequencing involving the sequencing of native RNA strands. The latter strategy, ultracentrifugation, causes loss in genomic information due to its inability to retrieve unassembled viral RNA. To address this, we developed a novel application of current nucleic acid hybridization technologies for direct characterization of RNA. In particular, we modified a current enrichment protocol to capture whole viral native RNA genomes for downstream RNA assays to circumvent the abovementioned problems. This technique involves hybridization of biotinylated baits at 500 nucleotides (nt) intervals, stringent washes and release of free native RNA strands using DNase I treatment, with a turnaround time of about 6 h 15 min. RT-qPCR was used as the primary proof of concept that capture-based purification indeed removes host background. Subsequently, capture-based purification was applied to direct RNA sequencing as proof of concept that capture-based purification can be coupled with downstream RNA assays. We report that this protocol was able to successfully purify viral RNA by 561- to 791-fold. We also report that application of this protocol to direct RNA sequencing yielded a reduction in human host RNA background by 1580-fold, a 99.91% recovery of viral genome with at least 15× coverage, and a mean coverage across the genome of 120×. This report is, to the best of our knowledge, the first description of a capture-based purification method for assays that involve direct manipulation or characterisation of native RNA. This report also describes a successful application of capture-based purification as a direct RNA sequencing strategy that addresses certain limitations of current strategies in sequencing RNA viral genomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13568-019-0772-y) contains supplementary material, which is available to authorized users.",2019 Apr 8,"['Tan, Cedric Chih Shen', 'Maurer-Stroh, Sebastian', 'Wan, Yue', 'Sessions, October Michael', 'de Sessions, Paola Florez']",AMB Express,,,True
f0384ad1acd95e489c5d835a494de1cdd3fd365f,PMC,The role of microglia in viral encephalitis: a review,http://dx.doi.org/10.1186/s12974-019-1443-2,PMC6454758,30967139,CC BY,"Viral encephalitis is still very prominent around the world, and traditional antiviral therapies still have shortcomings. Some patients cannot get effective relief or suffer from serious sequelae. At present, people are studying the role of the innate immune system in viral encephalitis. Microglia, as resident cells of the central nervous system (CNS), can respond quickly to various CNS injuries including trauma, ischemia, and infection and maintain the homeostasis of CNS, but this response is not always good; sometimes, it will exacerbate damage. Studies have shown that microglia also act as a double-edged sword during viral encephalitis. On the one hand, microglia can sense ATP signals through the purinergic receptor P2Y12 and are recruited around infected neurons to exert phagocytic activity. Microglia can exert a direct antiviral effect by producing type 1 interferon (IFN-1) to induce IFN-stimulated gene (ISG) expression of themselves or indirect antiviral effects by IFN-1 acting on other cells to activate corresponding signaling pathways. In addition, microglia can also exert an antiviral effect by inducing autophagy or secreting cytokines. On the other hand, microglia mediate presynaptic membrane damage in the hippocampus through complement, resulting in long-term memory impairment and cognitive dysfunction in patients with encephalitis. Microglia mediate fetal congenital malformations caused by Zika virus (ZIKV) infection. The gene expression profile of microglia in HIV encephalitis changes, and they tend to be a pro-inflammatory type. Microglia inhibited neuronal autophagy and aggravated the damage of CNS in HIV encephalitis; E3 ubiquitin ligase Pellino (pelia) expressed by microglia promotes the replication of virus in neurons. The interaction between amyloid-β peptide (Aβ) produced by neurons and activated microglia during viral infection is uncertain. Although neurons can mediate antiviral effects by activating receptor-interacting protein kinases 3 (RIPK3) in a death-independent pathway, the RIPK3 pathway of microglia is unknown. Different brain regions have different susceptibility to viruses, and the gene expression of microglia in different brain regions is specific. The relationship between the two needs to be further confirmed. How to properly regulate the function of microglia and make it exert more anti-inflammatory effects is our next research direction.",2019 Apr 9,"['Chen, Zhuangzhuang', 'Zhong, Di', 'Li, Guozhong']",J Neuroinflammation,,,True
db2710799be5aaa4eacbc75a921c6d4cc9364538,PMC,Middle East respiratory syndrome coronavirus infection in non-camelid domestic mammals,http://dx.doi.org/10.1080/22221751.2018.1560235,PMC6455111,30866764,CC BY,"Dromedary camels are natural host of the Middle East respiratory syndrome coronavirus (MERS-CoV). However, there are limited studies of MERS-CoV infection of other domestic mammals exposed to infected dromedaries. We expanded our surveillance among camels in Egypt, Tunisia, and Senegal to include other domestic mammalian species in contact with infected camels. A total of 820 sera and 823 nasal swabs from cattle, sheep, goats, donkeys, buffaloes, mules, and horses were collected. Swabs were tested using RT-PCR and virus RNA-positive samples were genetically sequenced and phylogenetically analysed. Sera were screened using virus microneutralization tests and positive sera (where available) were confirmed using plaque reduction neutralization tests (PRNT). We detected 90% PRNT confirmed MERS-CoV antibody in 35 (55.6%) of 63 sera from sheep collected from Senegal, two sheep (1.8%) of 114 in Tunisia and a goat (0.9%) of 107 in Egypt, with titres ranging from 1:80 to ≥1:320. We detected MERS-CoV RNA in swabs from three sheep (1.2%) of 254 and five goats (4.1%) of 121 from Egypt and Senegal, as well as one cow (1.9%) of 53 and three donkeys (7.1%) of 42 from Egypt. Partial sequences of the RT-PCR amplicons confirmed specificity of the results. This study showed that domestic livestock in contact with MERS-CoV infected camels may be at risk of infection. We recommend expanding current MERS-CoV surveillance in animals to include other livestock in close contact with dromedary camels. The segregation of camels from other livestock in farms and live animal markets may need to be considered.",2019 Jan 16,"['Kandeil, Ahmed', 'Gomaa, Mokhtar', 'Shehata, Mahmoud', 'El-Taweel, Ahmed', 'Kayed, Ahmed E.', 'Abiadh, Awatef', 'Jrijer, Jamel', 'Moatasim, Yassmin', 'Kutkat, Omnia', 'Bagato, Ola', 'Mahmoud, Sara', 'Mostafa, Ahmed', 'El-Shesheny, Rabeh', 'Perera, Ranawaka APM', 'Ko, Ronald LW', 'Hassan, Nagla', 'Elsokary, Basma', 'Allal, Lotfi', 'Saad, Ahmed', 'Sobhy, Heba', 'McKenzie, Pamela P.', 'Webby, Richard J.', 'Peiris, Malik', 'Ali, Mohamed A.', 'Kayali, Ghazi']",Emerg Microbes Infect,,,True
5581ec03ebdca073e13b0df6329779940908f038,PMC,Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein,http://dx.doi.org/10.1080/22221751.2019.1597644,PMC6455120,30938227,CC BY,"The Middle-East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus that causes severe and often fatal respiratory disease in humans. Efforts to develop antibody-based therapies have focused on neutralizing antibodies that target the receptor binding domain of the viral spike protein thereby blocking receptor binding. Here, we developed a set of human monoclonal antibodies that target functionally distinct domains of the MERS-CoV spike protein. These antibodies belong to six distinct epitope groups and interfere with the three critical entry functions of the MERS-CoV spike protein: sialic acid binding, receptor binding and membrane fusion. Passive immunization with potently as well as with poorly neutralizing antibodies protected mice from lethal MERS-CoV challenge. Collectively, these antibodies offer new ways to gain humoral protection in humans against the emerging MERS-CoV by targeting different spike protein epitopes and functions.",2019 Apr 2,"['Widjaja, Ivy', 'Wang, Chunyan', 'van Haperen, Rien', 'Gutiérrez-Álvarez, Javier', 'van Dieren, Brenda', 'Okba, Nisreen M.A.', 'Raj, V. Stalin', 'Li, Wentao', 'Fernandez-Delgado, Raul', 'Grosveld, Frank', 'van Kuppeveld, Frank J. M.', 'Haagmans, Bart L.', 'Enjuanes, Luis', 'Drabek, Dubravka', 'Bosch, Berend-Jan']",Emerg Microbes Infect,,,True
766f315970750baecd98b7fcc1a0ba8d7368d1cc,PMC,Protection against homo and hetero-subtypic influenza A virus by optimized M2e DNA vaccine,http://dx.doi.org/10.1080/22221751.2018.1558962,PMC6455129,30866759,CC BY,"Current influenza vaccines provide hemagglutinin strain-specific protection, but rarely provide cross-protection against divergent strains. It is, therefore, particularly important to develop a universal vaccine against conserved proteins or conserved regions of the virus. In this study, we used N-terminal extracellular region of the influenza virus M2 protein (M2e) as the target antigen and constructed two optimized M2e DNA vaccines (p-tPA-p3M2e and p-p3M2e) with increased antigenic epitope density and enhanced antigen secretion. Both vaccines induced high M2e-specific humoral and cellular immune responses in the vaccinated mice. These two vaccines also conferred protection against a lethal infection of homo-subtypic H1N1 virus, with p-tPA-p3M2e being the most effective. In addition, p-tPA-p3M2e also showed cross-protection against different subtypes of the influenza virus (H9N2, H6N6, and H10N8) at varying rates (80%, 40%, and 20%, respectively). After passive immunization, M2e DNA vaccine-induced antibodies in the sera provided complete protection against homologous virus challenge. An analysis of the mechanism underlying this immunization-mediated protection indicates that M2e-specific IgG and T-cell immune responses may play critical roles in the prevention of infection and viral clearance. Taken together, our results indicate that this optimized M2e DNA vaccine is a promising candidate for the development of a universal, broad-spectrum influenza virus vaccine.",2019 Jan 16,"['Yao, Yanfeng', 'Wang, Huadong', 'Chen, Jianjun', 'Shao, Zhiyong', 'He, Bin', 'Chen, Jie', 'Lan, Jiaming', 'Chen, Quanjiao', 'Chen, Ze']",Emerg Microbes Infect,,,True
5bf2ab79a25fdb03f50dafb0d08de60acbd50af0,PMC,"Cell surface α2,3-linked sialic acid facilitates Zika virus internalization",http://dx.doi.org/10.1080/22221751.2019.1590130,PMC6455136,30898036,CC BY,"The emergence of neurotropic Zika virus (ZIKV) raised a public health emergency of global concern. ZIKV can cross the placental barrier and infect foetal brains, resulting in microcephaly, but the pathogenesis of ZIKV is poorly understood. With recent findings reporting AXL as a type I interferon antagonist rather than an entry receptor, the exact entry mechanism remains unresolved. Here we report that cell surface sialic acid plays an important role in ZIKV infection. Removal of cell surface sialic acid by neuraminidase significantly abolished ZIKV infection in Vero cells and human induced-pluripotent stem cells-derived neural progenitor cells. Furthermore, knockout of the sialic acid biosynthesis gene encoding UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase resulted in significantly less ZIKV infection of both African and Asian lineages. Huh7 cells deficient in α2,3-linked sialic acid through knockout of ST3 β-galactoside-α2,3-sialyltransferase 4 had significantly reduced ZIKV infection. Removal of membrane-bound, un-internalized virus with pronase treatment revealed the role of sialic acid in ZIKV internalization but not attachment. Sialyllactose inhibition studies showed that there is no direct interaction between sialic acid and ZIKV, implying that sialic acid could be mediating ZIKV-receptor complex internalization. Identification of α2,3-linked sialic acid as an important host factor for ZIKV internalization provides new insight into ZIKV infection and pathogenesis.",2019 Mar 22,"['Tan, Chee Wah', 'Huan Hor, Catherine Hong', 'Kwek, Swee Sen', 'Tee, Han Kang', 'Sam, I-Ching', 'Goh, Eyleen L. K.', 'Ooi, Eng Eong', 'Chan, Yoke Fun', 'Wang, Lin-Fa']",Emerg Microbes Infect,,,True
57a145d6bea3653336fdd964a6d1e0494c32fcf4,PMC,Simultaneous outbreaks of respiratory disease in wild chimpanzees caused by distinct viruses of human origin,http://dx.doi.org/10.1080/22221751.2018.1563456,PMC6455141,30866768,CC BY,"Respiratory viruses of human origin infect wild apes across Africa, sometimes lethally. Here we report simultaneous outbreaks of two distinct human respiratory viruses, human metapneumovirus (MPV; Pneumoviridae: Metapneumovirus) and human respirovirus 3 (HRV3; Paramyxoviridae; Respirovirus, formerly known as parainfluenza virus 3), in two chimpanzee (Pan troglodytes schweinfurthii) communities in the same forest in Uganda in December 2016 and January 2017. The viruses were absent before the outbreaks, but each was present in ill chimpanzees from one community during the outbreak period. Clinical signs and gross pathologic changes in affected chimpanzees closely mirrored symptoms and pathology commonly observed in humans for each virus. Epidemiologic modelling showed that MPV and HRV3 were similarly transmissible (R(0) of 1.27 and 1.48, respectively), but MPV caused 12.2% mortality mainly in infants and older chimpanzees, whereas HRV3 caused no direct mortality. These results are consistent with the higher virulence of MPV than HRV3 in humans, although both MPV and HRV3 cause a significant global disease burden. Both viruses clustered phylogenetically within groups of known human variants, with MPV closely related to a lethal 2009 variant from mountain gorillas (Gorilla beringei beringei), suggesting two independent and simultaneous reverse zoonotic origins, either directly from humans or via intermediary hosts. These findings expand our knowledge of human origin viruses threatening wild chimpanzees and suggest that such viruses might be differentiated by their comparative epidemiological dynamics and pathogenicity in wild apes. Our results also caution against assuming common causation in coincident outbreaks.",2019 Jan 21,"['Negrey, Jacob D.', 'Reddy, Rachna B.', 'Scully, Erik J.', 'Phillips-Garcia, Sarah', 'Owens, Leah A.', 'Langergraber, Kevin E.', 'Mitani, John C.', 'Emery Thompson, Melissa', 'Wrangham, Richard W.', 'Muller, Martin N.', 'Otali, Emily', 'Machanda, Zarin', 'Hyeroba, David', 'Grindle, Kristine A.', 'Pappas, Tressa E.', 'Palmenberg, Ann C.', 'Gern, James E.', 'Goldberg, Tony L.']",Emerg Microbes Infect,,,True
0b9583908e91f87840a0f844e7c4ebb546482c50,PMC,Prospective case-control analysis of the aetiologies of acute undifferentiated fever in Vietnam,http://dx.doi.org/10.1080/22221751.2019.1580539,PMC6455186,30866787,CC BY,"Acute undifferentiated fever (AUF) is frequently observed in tropical settings, but diagnosing the cause of AUF is often a challenge for local physicians and the physicians treating returning travellers. We conducted a case-control study in central Vietnam in 2016. A total of 378 febrile adult patients (AUFs) with a fever for ≤21 days, no evidence of localized infection and negative screening tests for dengue and malaria, and 384 afebrile adult patients (Controls) were prospectively enrolled. Whole blood, plasma, eschar swab, throat swab and urine specimens were collected and analysed. Quantitative PCR and RT-PCR were used to test for 55 bacteria, viruses and their subtypes. Serological tests were also used to test for rickettsial agents. The most common aetiology was influenza virus (20.9% in AUFs vs. 0% in Controls), followed by rickettsial agents (mainly Orientia tsutsugamushi and Rickettsia typhi) (10.8% vs. 0.3%), dengue virus (7.7% vs. 0.5%), Leptospira (4.8% vs. 0.8%), adenovirus (4.8% vs. 1.0%), and enterovirus (2.1% vs. 0%) (p < .05). The real proportion of dengue in AUF cases was underestimated because patients with dengue-positive rapid diagnosis tests were excluded from the study. The emerging agent Rickettsia felis, which had not been previously observed in Vietnam, was detected in this study. In total, 216 patients (57.1%) were given causative diagnoses, comprising 143 (66.2%) monoinfections and 73 (33.8%) coinfections. The infections caused by these agents should be considered in clinical practice and further studies. Additionally, agents susceptible to doxycycline were detected in 15.6% of AUFs; thus, this drug should be included in the panel used to treat AUF patients.",2019 Mar 4,"['Le-Viet, Nhiem', 'Le, Viet-Nho', 'Chung, Hai', 'Phan, Duc-Tuan', 'Phan, Quang-Duong', 'Cao, Thanh-Van', 'Abat, Cédric', 'Raoult, Didier', 'Parola, Philippe']",Emerg Microbes Infect,,,True
2c3fc2c522ed72e939effed158240c1c971fbdad,PMC,Neuraminidase activity and specificity of influenza A virus are influenced by haemagglutinin-receptor binding,http://dx.doi.org/10.1080/22221751.2019.1581034,PMC6455212,30866786,CC BY,"Influenza virus haemagglutinin (HA) and neuraminidase (NA) are involved in the recognition and modulation of sialic acids on the cell surface as the virus receptor. Although the balance between two proteins functions has been found to be crucial for viral fitness, the interplay between the proteins has not been well established. Herein we present evidence for interplay between influenza HA and NA, which may affect the balance between two glycoprotein functions. NA enzymatic activities against sialoglycans were promoted by the presence of HA, which is in accordance with the level of co-existing HA. Such activity enhancement was lost when the HA-receptor binding properties were abolished by low-pH treatment or by mutations at the HA receptor binding domain. Sialidase activities of NA-containing virus-like particles and native influenza viruses were detected using different NA-assays and sialic acid substrates. Most pronounced HA-mediated NA enhancement was found when intact virions were confronted with multivalent surface-anchored substrates, which mimics the physiological conditions on cell membranes. Using recombinant viruses with altered HA bindings preference between α2,3- and α2,6-linked sialic acids, we also found that NA function against different substrates is correlated with the HA-receptor specificity. The effect of HA-receptor specificities on NA functions, together with the HA-mediated NA enhancement, may play a role in virus evasion of the mucus barrier, as well as in cross-species adaptation. Our data also indicate the importance of using multivalent substrates in future studies of NA functions.",2019 Feb 27,"['Lai, Jimmy Chun Cheong', 'Karunarathna, Herath M. T. K.', 'Wong, Ho Him', 'Peiris, Joseph S. M.', 'Nicholls, John M.']",Emerg Microbes Infect,,,True
4dee76896810956dac4627041734652c1c953947,PMC,A viral metagenomic survey identifies known and novel mammalian viruses in bats from Saudi Arabia,http://dx.doi.org/10.1371/journal.pone.0214227,PMC6457491,30969980,CC BY,"Bats are implicated as natural reservoirs for a wide range of zoonotic viruses including SARS and MERS coronaviruses, Ebola, Marburg, Nipah, Hendra, Rabies and other lyssaviruses. Accordingly, many One Health surveillance and viral discovery programs have focused on bats. In this report we present viral metagenomic data from bats collected in the Kingdom of Saudi Arabia [KSA]. Unbiased high throughput sequencing of fecal samples from 72 bat individuals comprising four species; lesser mouse-tailed bat (Rhinopoma hardwickii), Egyptian tomb bat (Taphozous perforatus), straw-colored fruit bat (Eidolon helvum), and Egyptian fruit bat (Rousettus aegyptiacus) revealed molecular evidence of a diverse set of viral families: Picornaviridae (hepatovirus, teschovirus, parechovirus), Reoviridae (rotavirus), Polyomaviridae (polyomavirus), Papillomaviridae (papillomavirus), Astroviridae (astrovirus), Caliciviridae (sapovirus), Coronaviridae (coronavirus), Adenoviridae (adenovirus), Paramyxoviridae (paramyxovirus), and unassigned mononegavirales (chuvirus). Additionally, we discovered a bastro-like virus (Middle East Hepe-Astrovirus), with a genomic organization similar to Hepeviridae. However, since it shared homology with Hepeviridae and Astroviridae at ORF1 and in ORF2, respectively, the newly discovered Hepe-Astrovirus may represent a phylogenetic bridge between Hepeviridae and Astroviridae.",2019 Apr 10,"['Mishra, Nischay', 'Fagbo, Shamsudeen F.', 'Alagaili, Abdulaziz N.', 'Nitido, Adam', 'Williams, Simon H.', 'Ng, James', 'Lee, Bohyun', 'Durosinlorun, Abdulkareem', 'Garcia, Joel A.', 'Jain, Komal', 'Kapoor, Vishal', 'Epstein, Jonathan H.', 'Briese, Thomas', 'Memish, Ziad A.', 'Olival, Kevin J.', 'Lipkin, W. Ian']",PLoS One,,,True
84a70ff7ffa970c018c38f4f80cc2f2610e7ec9d,PMC,A viral metagenomic survey identifies known and novel mammalian viruses in bats from Saudi Arabia,http://dx.doi.org/10.1371/journal.pone.0214227,PMC6457491,30969980,CC BY,"Bats are implicated as natural reservoirs for a wide range of zoonotic viruses including SARS and MERS coronaviruses, Ebola, Marburg, Nipah, Hendra, Rabies and other lyssaviruses. Accordingly, many One Health surveillance and viral discovery programs have focused on bats. In this report we present viral metagenomic data from bats collected in the Kingdom of Saudi Arabia [KSA]. Unbiased high throughput sequencing of fecal samples from 72 bat individuals comprising four species; lesser mouse-tailed bat (Rhinopoma hardwickii), Egyptian tomb bat (Taphozous perforatus), straw-colored fruit bat (Eidolon helvum), and Egyptian fruit bat (Rousettus aegyptiacus) revealed molecular evidence of a diverse set of viral families: Picornaviridae (hepatovirus, teschovirus, parechovirus), Reoviridae (rotavirus), Polyomaviridae (polyomavirus), Papillomaviridae (papillomavirus), Astroviridae (astrovirus), Caliciviridae (sapovirus), Coronaviridae (coronavirus), Adenoviridae (adenovirus), Paramyxoviridae (paramyxovirus), and unassigned mononegavirales (chuvirus). Additionally, we discovered a bastro-like virus (Middle East Hepe-Astrovirus), with a genomic organization similar to Hepeviridae. However, since it shared homology with Hepeviridae and Astroviridae at ORF1 and in ORF2, respectively, the newly discovered Hepe-Astrovirus may represent a phylogenetic bridge between Hepeviridae and Astroviridae.",2019 Apr 10,"['Mishra, Nischay', 'Fagbo, Shamsudeen F.', 'Alagaili, Abdulaziz N.', 'Nitido, Adam', 'Williams, Simon H.', 'Ng, James', 'Lee, Bohyun', 'Durosinlorun, Abdulkareem', 'Garcia, Joel A.', 'Jain, Komal', 'Kapoor, Vishal', 'Epstein, Jonathan H.', 'Briese, Thomas', 'Memish, Ziad A.', 'Olival, Kevin J.', 'Lipkin, W. Ian']",PLoS One,,,False
e26f7232da3f45c27bcb6ef5c5c8d168c307bfd1,PMC,A viral metagenomic survey identifies known and novel mammalian viruses in bats from Saudi Arabia,http://dx.doi.org/10.1371/journal.pone.0214227,PMC6457491,30969980,CC BY,"Bats are implicated as natural reservoirs for a wide range of zoonotic viruses including SARS and MERS coronaviruses, Ebola, Marburg, Nipah, Hendra, Rabies and other lyssaviruses. Accordingly, many One Health surveillance and viral discovery programs have focused on bats. In this report we present viral metagenomic data from bats collected in the Kingdom of Saudi Arabia [KSA]. Unbiased high throughput sequencing of fecal samples from 72 bat individuals comprising four species; lesser mouse-tailed bat (Rhinopoma hardwickii), Egyptian tomb bat (Taphozous perforatus), straw-colored fruit bat (Eidolon helvum), and Egyptian fruit bat (Rousettus aegyptiacus) revealed molecular evidence of a diverse set of viral families: Picornaviridae (hepatovirus, teschovirus, parechovirus), Reoviridae (rotavirus), Polyomaviridae (polyomavirus), Papillomaviridae (papillomavirus), Astroviridae (astrovirus), Caliciviridae (sapovirus), Coronaviridae (coronavirus), Adenoviridae (adenovirus), Paramyxoviridae (paramyxovirus), and unassigned mononegavirales (chuvirus). Additionally, we discovered a bastro-like virus (Middle East Hepe-Astrovirus), with a genomic organization similar to Hepeviridae. However, since it shared homology with Hepeviridae and Astroviridae at ORF1 and in ORF2, respectively, the newly discovered Hepe-Astrovirus may represent a phylogenetic bridge between Hepeviridae and Astroviridae.",2019 Apr 10,"['Mishra, Nischay', 'Fagbo, Shamsudeen F.', 'Alagaili, Abdulaziz N.', 'Nitido, Adam', 'Williams, Simon H.', 'Ng, James', 'Lee, Bohyun', 'Durosinlorun, Abdulkareem', 'Garcia, Joel A.', 'Jain, Komal', 'Kapoor, Vishal', 'Epstein, Jonathan H.', 'Briese, Thomas', 'Memish, Ziad A.', 'Olival, Kevin J.', 'Lipkin, W. Ian']",PLoS One,,,False
37b75d1e51b3528bbf10b56bb9baf97e81d09d89,PMC,A viral metagenomic survey identifies known and novel mammalian viruses in bats from Saudi Arabia,http://dx.doi.org/10.1371/journal.pone.0214227,PMC6457491,30969980,CC BY,"Bats are implicated as natural reservoirs for a wide range of zoonotic viruses including SARS and MERS coronaviruses, Ebola, Marburg, Nipah, Hendra, Rabies and other lyssaviruses. Accordingly, many One Health surveillance and viral discovery programs have focused on bats. In this report we present viral metagenomic data from bats collected in the Kingdom of Saudi Arabia [KSA]. Unbiased high throughput sequencing of fecal samples from 72 bat individuals comprising four species; lesser mouse-tailed bat (Rhinopoma hardwickii), Egyptian tomb bat (Taphozous perforatus), straw-colored fruit bat (Eidolon helvum), and Egyptian fruit bat (Rousettus aegyptiacus) revealed molecular evidence of a diverse set of viral families: Picornaviridae (hepatovirus, teschovirus, parechovirus), Reoviridae (rotavirus), Polyomaviridae (polyomavirus), Papillomaviridae (papillomavirus), Astroviridae (astrovirus), Caliciviridae (sapovirus), Coronaviridae (coronavirus), Adenoviridae (adenovirus), Paramyxoviridae (paramyxovirus), and unassigned mononegavirales (chuvirus). Additionally, we discovered a bastro-like virus (Middle East Hepe-Astrovirus), with a genomic organization similar to Hepeviridae. However, since it shared homology with Hepeviridae and Astroviridae at ORF1 and in ORF2, respectively, the newly discovered Hepe-Astrovirus may represent a phylogenetic bridge between Hepeviridae and Astroviridae.",2019 Apr 10,"['Mishra, Nischay', 'Fagbo, Shamsudeen F.', 'Alagaili, Abdulaziz N.', 'Nitido, Adam', 'Williams, Simon H.', 'Ng, James', 'Lee, Bohyun', 'Durosinlorun, Abdulkareem', 'Garcia, Joel A.', 'Jain, Komal', 'Kapoor, Vishal', 'Epstein, Jonathan H.', 'Briese, Thomas', 'Memish, Ziad A.', 'Olival, Kevin J.', 'Lipkin, W. Ian']",PLoS One,,,False
63b2d52e6516fa5507982a0fbb3fa481f5baa7b2,PMC,A viral metagenomic survey identifies known and novel mammalian viruses in bats from Saudi Arabia,http://dx.doi.org/10.1371/journal.pone.0214227,PMC6457491,30969980,CC BY,"Bats are implicated as natural reservoirs for a wide range of zoonotic viruses including SARS and MERS coronaviruses, Ebola, Marburg, Nipah, Hendra, Rabies and other lyssaviruses. Accordingly, many One Health surveillance and viral discovery programs have focused on bats. In this report we present viral metagenomic data from bats collected in the Kingdom of Saudi Arabia [KSA]. Unbiased high throughput sequencing of fecal samples from 72 bat individuals comprising four species; lesser mouse-tailed bat (Rhinopoma hardwickii), Egyptian tomb bat (Taphozous perforatus), straw-colored fruit bat (Eidolon helvum), and Egyptian fruit bat (Rousettus aegyptiacus) revealed molecular evidence of a diverse set of viral families: Picornaviridae (hepatovirus, teschovirus, parechovirus), Reoviridae (rotavirus), Polyomaviridae (polyomavirus), Papillomaviridae (papillomavirus), Astroviridae (astrovirus), Caliciviridae (sapovirus), Coronaviridae (coronavirus), Adenoviridae (adenovirus), Paramyxoviridae (paramyxovirus), and unassigned mononegavirales (chuvirus). Additionally, we discovered a bastro-like virus (Middle East Hepe-Astrovirus), with a genomic organization similar to Hepeviridae. However, since it shared homology with Hepeviridae and Astroviridae at ORF1 and in ORF2, respectively, the newly discovered Hepe-Astrovirus may represent a phylogenetic bridge between Hepeviridae and Astroviridae.",2019 Apr 10,"['Mishra, Nischay', 'Fagbo, Shamsudeen F.', 'Alagaili, Abdulaziz N.', 'Nitido, Adam', 'Williams, Simon H.', 'Ng, James', 'Lee, Bohyun', 'Durosinlorun, Abdulkareem', 'Garcia, Joel A.', 'Jain, Komal', 'Kapoor, Vishal', 'Epstein, Jonathan H.', 'Briese, Thomas', 'Memish, Ziad A.', 'Olival, Kevin J.', 'Lipkin, W. Ian']",PLoS One,,,False
ddfd4e3e6da765f46ae404d52a3236d35669189f,PMC,A viral metagenomic survey identifies known and novel mammalian viruses in bats from Saudi Arabia,http://dx.doi.org/10.1371/journal.pone.0214227,PMC6457491,30969980,CC BY,"Bats are implicated as natural reservoirs for a wide range of zoonotic viruses including SARS and MERS coronaviruses, Ebola, Marburg, Nipah, Hendra, Rabies and other lyssaviruses. Accordingly, many One Health surveillance and viral discovery programs have focused on bats. In this report we present viral metagenomic data from bats collected in the Kingdom of Saudi Arabia [KSA]. Unbiased high throughput sequencing of fecal samples from 72 bat individuals comprising four species; lesser mouse-tailed bat (Rhinopoma hardwickii), Egyptian tomb bat (Taphozous perforatus), straw-colored fruit bat (Eidolon helvum), and Egyptian fruit bat (Rousettus aegyptiacus) revealed molecular evidence of a diverse set of viral families: Picornaviridae (hepatovirus, teschovirus, parechovirus), Reoviridae (rotavirus), Polyomaviridae (polyomavirus), Papillomaviridae (papillomavirus), Astroviridae (astrovirus), Caliciviridae (sapovirus), Coronaviridae (coronavirus), Adenoviridae (adenovirus), Paramyxoviridae (paramyxovirus), and unassigned mononegavirales (chuvirus). Additionally, we discovered a bastro-like virus (Middle East Hepe-Astrovirus), with a genomic organization similar to Hepeviridae. However, since it shared homology with Hepeviridae and Astroviridae at ORF1 and in ORF2, respectively, the newly discovered Hepe-Astrovirus may represent a phylogenetic bridge between Hepeviridae and Astroviridae.",2019 Apr 10,"['Mishra, Nischay', 'Fagbo, Shamsudeen F.', 'Alagaili, Abdulaziz N.', 'Nitido, Adam', 'Williams, Simon H.', 'Ng, James', 'Lee, Bohyun', 'Durosinlorun, Abdulkareem', 'Garcia, Joel A.', 'Jain, Komal', 'Kapoor, Vishal', 'Epstein, Jonathan H.', 'Briese, Thomas', 'Memish, Ziad A.', 'Olival, Kevin J.', 'Lipkin, W. Ian']",PLoS One,,,False
d486d51868e8d420880e5f21ae906a5150642763,PMC,"Bayesian inference of transmission chains using timing of symptoms, pathogen genomes and contact data",http://dx.doi.org/10.1371/journal.pcbi.1006930,PMC6457559,30925168,CC BY,"There exists significant interest in developing statistical and computational tools for inferring ‘who infected whom’ in an infectious disease outbreak from densely sampled case data, with most recent studies focusing on the analysis of whole genome sequence data. However, genomic data can be poorly informative of transmission events if mutations accumulate too slowly to resolve individual transmission pairs or if there exist multiple pathogens lineages within-host, and there has been little focus on incorporating other types of outbreak data. We present here a methodology that uses contact data for the inference of transmission trees in a statistically rigorous manner, alongside genomic data and temporal data. Contact data is frequently collected in outbreaks of pathogens spread by close contact, including Ebola virus (EBOV), severe acute respiratory syndrome coronavirus (SARS-CoV) and Mycobacterium tuberculosis (TB), and routinely used to reconstruct transmission chains. As an improvement over previous, ad-hoc approaches, we developed a probabilistic model that relates a set of contact data to an underlying transmission tree and integrated this in the outbreaker2 inference framework. By analyzing simulated outbreaks under various contact tracing scenarios, we demonstrate that contact data significantly improves our ability to reconstruct transmission trees, even under realistic limitations on the coverage of the contact tracing effort and the amount of non-infectious mixing between cases. Indeed, contact data is equally or more informative than fully sampled whole genome sequence data in certain scenarios. We then use our method to analyze the early stages of the 2003 SARS outbreak in Singapore and describe the range of transmission scenarios consistent with contact data and genetic sequence in a probabilistic manner for the first time. This simple yet flexible model can easily be incorporated into existing tools for outbreak reconstruction and should permit a better integration of genomic and epidemiological data for inferring transmission chains.",2019 Mar 29,"['Campbell, Finlay', 'Cori, Anne', 'Ferguson, Neil', 'Jombart, Thibaut']",PLoS Comput Biol,,,True
0dbd0395f35ca86b7afb6e0325025b8741dfa771,PMC,Emerging infectious diseases and biological invasions: a call for a One Health collaboration in science and management,http://dx.doi.org/10.1098/rsos.181577,PMC6458372,31032015,CC BY,"The study and management of emerging infectious diseases (EIDs) and of biological invasions both address the ecology of human-associated biological phenomena in a rapidly changing world. However, the two fields work mostly in parallel rather than in concert. This review explores how the general phenomenon of an organism rapidly increasing in range or abundance is caused, highlights the similarities and differences between research on EIDs and invasions, and discusses shared management insights and approaches. EIDs can arise by: (i) crossing geographical barriers due to human-mediated dispersal, (ii) crossing compatibility barriers due to evolution, and (iii) lifting of environmental barriers due to environmental change. All these processes can be implicated in biological invasions, but only the first defines them. Research on EIDs is embedded within the One Health concept—the notion that human, animal and ecosystem health are interrelated and that holistic approaches encompassing all three components are needed to respond to threats to human well-being. We argue that for sustainable development, biological invasions should be explicitly considered within One Health. Management goals for the fields are the same, and direct collaborations between invasion scientists, disease ecologists and epidemiologists on modelling, risk assessment, monitoring and management would be mutually beneficial.",2019 Mar 13,"['Ogden, Nick H.', 'Wilson, John R. U.', 'Richardson, David M.', 'Hui, Cang', 'Davies, Sarah J.', 'Kumschick, Sabrina', 'Le Roux, Johannes J.', 'Measey, John', 'Saul, Wolf-Christian', 'Pulliam, Juliet R. C.']",R Soc Open Sci,,,True
1cc3a2b915e37c3c5cd03367a734c6c7c1ca4e6e,PMC,Emerging infectious diseases and biological invasions: a call for a One Health collaboration in science and management,http://dx.doi.org/10.1098/rsos.181577,PMC6458372,31032015,CC BY,"The study and management of emerging infectious diseases (EIDs) and of biological invasions both address the ecology of human-associated biological phenomena in a rapidly changing world. However, the two fields work mostly in parallel rather than in concert. This review explores how the general phenomenon of an organism rapidly increasing in range or abundance is caused, highlights the similarities and differences between research on EIDs and invasions, and discusses shared management insights and approaches. EIDs can arise by: (i) crossing geographical barriers due to human-mediated dispersal, (ii) crossing compatibility barriers due to evolution, and (iii) lifting of environmental barriers due to environmental change. All these processes can be implicated in biological invasions, but only the first defines them. Research on EIDs is embedded within the One Health concept—the notion that human, animal and ecosystem health are interrelated and that holistic approaches encompassing all three components are needed to respond to threats to human well-being. We argue that for sustainable development, biological invasions should be explicitly considered within One Health. Management goals for the fields are the same, and direct collaborations between invasion scientists, disease ecologists and epidemiologists on modelling, risk assessment, monitoring and management would be mutually beneficial.",2019 Mar 13,"['Ogden, Nick H.', 'Wilson, John R. U.', 'Richardson, David M.', 'Hui, Cang', 'Davies, Sarah J.', 'Kumschick, Sabrina', 'Le Roux, Johannes J.', 'Measey, John', 'Saul, Wolf-Christian', 'Pulliam, Juliet R. C.']",R Soc Open Sci,,,False
8b9727ae8713013fe82481d87cf57529201353d3,PMC,Airflow analysis of Pyeongtaek St Mary's Hospital during hospitalization of the first Middle East respiratory syndrome patient in Korea,http://dx.doi.org/10.1098/rsos.181164,PMC6458380,31031996,CC BY,"Middle East respiratory syndrome (MERS) is known to be transmitted through close contact. However, epidemiological surveys of MERS in Korea indicated that some secondary patients were infected without close contact. Therefore, the possibility of other transmission routes must be identified. In this study, the possibility of MERS spreading through airflow was investigated on the eighth floor of Pyeongtaek St Mary's Hospital. Computational fluid dynamics was used to analyse the indoor airflow and passive tracer diffusion during the index patient's stay. Six cases were simulated for different outdoor wind directions and indoor mechanical ventilation operations. When a passive tracer was released in ward 8104, where the index patient was hospitalized, the passive tracer spread through the indoor airflow, which was created by the outdoor airflow. Ward 8109, which had the largest number of infected cases and was far distant from ward 8104, showed passive tracer concentration in all cases. This result indicates that MERS may have spread through airflow. The study results do not imply that the infection pathway of MERS is airborne. However, the results show the possibility of MERS spreading through airflow in specific environments such as poor ventilation environments.",2019 Mar 13,"['Jo, Seongmin', 'Hong, Jinkwan', 'Lee, Sang-Eun', 'Ki, Moran', 'Choi, Bo Youl', 'Sung, Minki']",R Soc Open Sci,,,True
dd65db968a579c422c2fc4e43bbf0b265b5b3ea6,PMC,Analysis of long non-coding RNAs in neonatal piglets at different stages of porcine deltacoronavirus infection,http://dx.doi.org/10.1186/s12917-019-1862-4,PMC6458635,30971240,CC BY,"BACKGROUND: PDCoV (Porcine Deltacoronavirus) is a novel porcine coronavirus that causes intestinal necrosis of piglets, thinning of the intestinal wall and severe villus atrophy in the small intestine. PDCoV is a highly contagious infectious disease characterized by diarrhea, dehydration and vomiting. It has been reported that lncRNA has a significant effect on viral replication and increased or decreased virulence. At present, there is almost no research on lncRNA related to PDCoV infection. With the development of the research, a large number of lncRNAs related to PDCoV infection have been discovered. Identifying the role of these lncRNAs in the infection process facilitates the screening of diagnostically significant biomarkers. RESULTS: Using high throughput sequencing to screen differentially expressed long non-coding RNA (lncRNA) during PDCoV infection, we identified 99, 41 and 33 differentially expressed lncRNAs in the early, middle and late stages of infection, respectively. These lncRNAs were involved in glycolysis / gluconeogenesis, histidine metabolism and pentose and Chloroalkane and chloroalkene degradation pathway. We obtained expression data of miRNAs, lncRNAs and mRNAs during PDCoV infection and constructed and investigated an interaction network. The qRT-PCR validation results of 6 differentially expressed lncRNAs were consistent with RNA-Seq results. CONCLUSIONS: This study is the first to examine differentially expressed lncRNAs after PDCoV infection of piglets. These results can provide new insights into PDCoV infection and antiviral strategies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-019-1862-4) contains supplementary material, which is available to authorized users.",2019 Apr 11,"['Tang, Xiaoyu', 'Lan, Tian', 'Wu, Ruiting', 'Zhou, Zhihai', 'Chen, Yuqi', 'Sun, Yuan', 'Zheng, Yaoyao', 'Ma, Jingyun']",BMC Vet Res,,,True
d33624f8b27d81d663f54d3e167aaf15968ff8a4,PMC,An OpenMP-based tool for finding longest common subsequence in bioinformatics,http://dx.doi.org/10.1186/s13104-019-4256-6,PMC6458724,30971295,CC BY,"OBJECTIVE: Finding the longest common subsequence (LCS) among sequences is NP-hard. This is an important problem in bioinformatics for DNA sequence alignment and pattern discovery. In this research, we propose new CPU-based parallel implementations that can provide significant advantages in terms of execution times, monetary cost, and pervasiveness in finding LCS of DNA sequences in an environment where Graphics Processing Units are not available. For general purpose use, we also make the OpenMP-based tool publicly available to end users. RESULT: In this study, we develop three novel parallel versions of the LCS algorithm on: (i) distributed memory machine using message passing interface (MPI); (ii) shared memory machine using OpenMP, and (iii) hybrid platform that utilizes both distributed and shared memory using MPI-OpenMP. The experimental results with both simulated and real DNA sequence data show that the shared memory OpenMP implementation provides at least two-times absolute speedup than the best sequential version of the algorithm and a relative speedup of almost 7. We provide a detailed comparison of the execution times among the implementations on different platforms with different versions of the algorithm. We also show that removing branch conditions negatively affects the performance of the CPU-based parallel algorithm on OpenMP platform.",2019 Apr 11,"['Shikder, Rayhan', 'Thulasiraman, Parimala', 'Irani, Pourang', 'Hu, Pingzhao']",BMC Res Notes,,,True
a769fe3dd7a63ddec2a0180ddd8a004050eaddc1,PMC,Whole genome characterisation of quail deltacoronavirus detected in Poland,http://dx.doi.org/10.1007/s11262-019-01639-1,PMC6458967,30758768,CC BY,"Quail deltacoronavirus (QdCoV) described for the first time in the United Arab Emirates in 2018 belongs to the same deltacoronavirus species as viruses discovered in swine and tree sparrows. The full-length genome of QdCoV detected in quails with enteritis in Poland has similar organization as Middle Eastern viruses although there is no NSP7c gene. The overall degree of nucleotide sequence identity was 92.4–92.6% between Polish PL/G032/2015 and Middle Eastern UAE-HKU30 QdCoV isolates. The sequences of the individual genes show similar nucleotide identities in the range of 91.4–94.7% with the exception of the S gene with lower identity of 85.6–85.7%. The most variable part of the S gene is its fragment encoding the N-terminal domain of the S protein which is responsible for receptor binding. The amino acid homology in this region between PL/G032/2015 and UAE-HKU30 QdCoVs was 74.5–74.7%. In contrast, the C-terminal domain of the S protein which is responsible for membrane fusion had an amino acid homology of 96.9%. In the phylogenetic tree, PL/G032/2015 branched separately but clustered with the UAE-HKU30 QdCoV isolates. These data suggest that PL/G032/2015 could be a new genetic/serologic variant of QdCoV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11262-019-01639-1) contains supplementary material, which is available to authorized users.",2019 Feb 13,"['Domańska-Blicharz, Katarzyna', 'Kuczkowski, Maciej', 'Sajewicz-Krukowska, Joanna']",Virus Genes,,,True
60da5c83bb867ca0f2f6eb9471d2bfc15c2b8d3e,PMC,"The Long Pentraxin PTX3 as a Link Between Innate Immunity, Tissue Remodeling, and Cancer",http://dx.doi.org/10.3389/fimmu.2019.00712,PMC6459138,31019517,CC BY,"The innate immune system comprises a cellular and a humoral arm. Humoral pattern recognition molecules include complement components, collectins, ficolins, and pentraxins. These molecules are involved in innate immune responses by recognizing microbial moieties and damaged tissues, activating complement, exerting opsonic activity and facilitating phagocytosis, and regulating inflammation. The long pentraxin PTX3 is a prototypic humoral pattern recognition molecule that, in addition to providing defense against infectious agents, plays several functions in tissue repair and regulation of cancer-related inflammation. Characterization of the PTX3 molecular structure and biochemical properties, and insights into its interactome and multiple roles in tissue damage and remodeling support the view that microbial and matrix recognition are evolutionarily conserved functions of humoral innate immunity molecules.",2019 Apr 4,"['Doni, Andrea', 'Stravalaci, Matteo', 'Inforzato, Antonio', 'Magrini, Elena', 'Mantovani, Alberto', 'Garlanda, Cecilia', 'Bottazzi, Barbara']",Front Immunol,,,True
57739f7172bb6dd11a63147d6bd37a3c227c7bc2,PMC,Inhibitors of signal peptide peptidase and subtilisin/kexin-isozyme 1 inhibit Ebola virus glycoprotein-driven cell entry by interfering with activity and cellular localization of endosomal cathepsins,http://dx.doi.org/10.1371/journal.pone.0214968,PMC6459477,30973897,CC BY,"Emerging viruses such as severe fever and thrombocytopenia syndrome virus (SFTSV) and Ebola virus (EBOV) are responsible for significant morbidity and mortality. Host cell proteases that process the glycoproteins of these viruses are potential targets for antiviral intervention. The aspartyl protease signal peptide peptidase (SPP) has recently been shown to be required for processing of the glycoprotein precursor, Gn/Gc, of Bunyamwera virus and for viral infectivity. Here, we investigated whether SPP is also required for infectivity of particles bearing SFTSV-Gn/Gc. Entry driven by the EBOV glycoprotein (GP) and the Lassa virus glycoprotein (LASV-GPC) depends on the cysteine proteases cathepsin B and L (CatB/CatL) and the serine protease subtilisin/kexin-isozyme 1 (SKI-1), respectively, and was examined in parallel for control purposes. We found that inhibition of SPP and SKI-1 did not interfere with SFTSV Gn + Gc-driven entry but, unexpectedly, blocked entry mediated by EBOV-GP. The inhibition occurred at the stage of proteolytic activation and the SPP inhibitor was found to block CatL/CatB activity. In contrast, the SKI-1 inhibitor did not interfere with CatB/CatL activity but disrupted CatB localization in endo/lysosomes, the site of EBOV-GP processing. These results underline the potential of protease inhibitors for antiviral therapy but also show that previously characterized compounds might exert broader specificity than initially appreciated and might block viral entry via diverse mechanisms.",2019 Apr 11,"['Plegge, Teresa', 'Spiegel, Martin', 'Krüger, Nadine', 'Nehlmeier, Inga', 'Winkler, Michael', 'González Hernández, Mariana', 'Pöhlmann, Stefan']",PLoS One,,,True
d12f9ba13588497fa3bf73a63b72dd77b78b0d5e,PMC,Inhibitors of signal peptide peptidase and subtilisin/kexin-isozyme 1 inhibit Ebola virus glycoprotein-driven cell entry by interfering with activity and cellular localization of endosomal cathepsins,http://dx.doi.org/10.1371/journal.pone.0214968,PMC6459477,30973897,CC BY,"Emerging viruses such as severe fever and thrombocytopenia syndrome virus (SFTSV) and Ebola virus (EBOV) are responsible for significant morbidity and mortality. Host cell proteases that process the glycoproteins of these viruses are potential targets for antiviral intervention. The aspartyl protease signal peptide peptidase (SPP) has recently been shown to be required for processing of the glycoprotein precursor, Gn/Gc, of Bunyamwera virus and for viral infectivity. Here, we investigated whether SPP is also required for infectivity of particles bearing SFTSV-Gn/Gc. Entry driven by the EBOV glycoprotein (GP) and the Lassa virus glycoprotein (LASV-GPC) depends on the cysteine proteases cathepsin B and L (CatB/CatL) and the serine protease subtilisin/kexin-isozyme 1 (SKI-1), respectively, and was examined in parallel for control purposes. We found that inhibition of SPP and SKI-1 did not interfere with SFTSV Gn + Gc-driven entry but, unexpectedly, blocked entry mediated by EBOV-GP. The inhibition occurred at the stage of proteolytic activation and the SPP inhibitor was found to block CatL/CatB activity. In contrast, the SKI-1 inhibitor did not interfere with CatB/CatL activity but disrupted CatB localization in endo/lysosomes, the site of EBOV-GP processing. These results underline the potential of protease inhibitors for antiviral therapy but also show that previously characterized compounds might exert broader specificity than initially appreciated and might block viral entry via diverse mechanisms.",2019 Apr 11,"['Plegge, Teresa', 'Spiegel, Martin', 'Krüger, Nadine', 'Nehlmeier, Inga', 'Winkler, Michael', 'González Hernández, Mariana', 'Pöhlmann, Stefan']",PLoS One,,,False
71e8fcabcecb3f5ce3a699f95a618bd21a68bd76,PMC,Synthetic surfactin analogues have improved anti-PEDV properties,http://dx.doi.org/10.1371/journal.pone.0215227,PMC6459484,30973929,CC BY,"Surfactin has antiviral activity against various enveloped viruses by inhibiting viral membrane fusion. However, the potential utility of surfactin as an antiviral drug is limited by its cytotoxicity. In this study, 10 surfactin analogues were obtained by chemical synthesis and evaluated to determine their anti-PEDV activities, hemolytic activities, and critical micelle concentrations. The main goal of our study was to develop a safer drug; a surfactin analogue with high anti-PEDV activity and low hemolytic activity. Compared with surfactin, one of the analogues we developed, SLP5, has lower hemolytic activity, with the same antiviral activity. The selectivity index of SLP5 is 52, while the SI for surfactin is 4, in other words, the safe and effective concentration range of SLP5 is 12 times greater than that of surfactin. Like surfactin, SLP5 has a direct antiviral effect on PEDV. Structurally, SLP5 is a linear lipopeptide with three carboxyl groups. Surfactin derivatives similar to SLP5 could be obtained by lactone bond hydrolyzation of surfactin, as well as total synthesis.",2019 Apr 11,"['Yuan, Lvfeng', 'Zhang, Shuai', 'Peng, Jie', 'Li, Yuchen', 'Yang, Qian']",PLoS One,,,True
185bc5c5addfa50d75d15b288537d11bd4a4aa5d,PMC,CRISPR screening using an expanded toolkit of autophagy reporters identifies TMEM41B as a novel autophagy factor,http://dx.doi.org/10.1371/journal.pbio.2007044,PMC6459555,30933966,CC BY,"The power of forward genetics in yeast is the foundation on which the field of autophagy research firmly stands. Complementary work on autophagy in higher eukaryotes has revealed both the deep conservation of this process, as well as novel mechanisms by which autophagy is regulated in the context of development, immunity, and neuronal homeostasis. The recent emergence of new clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-based technologies has begun facilitating efforts to define novel autophagy factors and pathways by forward genetic screening in mammalian cells. Here, we set out to develop an expanded toolkit of autophagy reporters amenable to CRISPR/Cas9 screening. Genome-wide screening of our reporters in mammalian cells recovered virtually all known autophagy-related (ATG) factors as well as previously uncharacterized factors, including vacuolar protein sorting 37 homolog A (VPS37A), transmembrane protein 251 (TMEM251), amyotrophic lateral sclerosis 2 (ALS2), and TMEM41B. To validate this data set, we used quantitative microscopy and biochemical analyses to show that 1 novel hit, TMEM41B, is required for phagophore maturation. TMEM41B is an integral endoplasmic reticulum (ER) membrane protein distantly related to the established autophagy factor vacuole membrane protein 1 (VMP1), and our data show that these two factors play related, albeit not fully overlapping, roles in autophagosome biogenesis. In sum, our work uncovers new ATG factors, reveals a malleable network of autophagy receptor genetic interactions, and provides a valuable resource (http://crispr.deniclab.com) for further mining of novel autophagy mechanisms.",2019 Apr 1,"['Shoemaker, Christopher J.', 'Huang, Tina Q.', 'Weir, Nicholas R.', 'Polyakov, Nicole J.', 'Schultz, Sebastian W.', 'Denic, Vladimir']",PLoS Biol,,,True
63fcbf2d0f0015b1b4ab01e20349ca7ee4c82dd4,PMC,"Genome Organization of Canada Goose Coronavirus, A Novel Species Identified in a Mass Die-off of Canada Geese",http://dx.doi.org/10.1038/s41598-019-42355-y,PMC6459860,30976080,CC BY,"The complete genome of a novel coronavirus was sequenced directly from the cloacal swab of a Canada goose that perished in a die-off of Canada and Snow geese in Cambridge Bay, Nunavut, Canada. Comparative genomics and phylogenetic analysis indicate it is a new species of Gammacoronavirus, as it falls below the threshold of 90% amino acid similarity in the protein domains used to demarcate Coronaviridae. Additional features that distinguish the genome of Canada goose coronavirus include 6 novel ORFs, a partial duplication of the 4 gene and a presumptive change in the proteolytic processing of polyproteins 1a and 1ab.",2019 Apr 11,"['Papineau, Amber', 'Berhane, Yohannes', 'Wylie, Todd N.', 'Wylie, Kristine M.', 'Sharpe, Samuel', 'Lung, Oliver']",Sci Rep,,,True
4465b8957219de75fb5b7f7ed57069405572cf00,PMC,Visibility and transmission: complexities around promoting hand hygiene in young children – a qualitative study,http://dx.doi.org/10.1186/s12889-019-6729-x,PMC6460784,30975108,CC BY,"BACKGROUND: Effective hand hygiene practice can reduce transmission of diseases such as respiratory tract infections (RTIs) and gastrointestinal infections, especially in young children. While hand hygiene has been widely promoted within Australia, primary care providers’ (PCPs) and parents’ understanding of hand hygiene importance, and their views on hand hygiene in reducing transmission of diseases in the community are unclear. Therefore, the aim of this study was to explore the views of PCPs and parents of young children on their knowledge and practice of hand hygiene in disease transmission. METHODS: Using a cross-sectional qualitative research design, we conducted 30 in-depth interviews with PCPs and five focus groups with parents (n = 50) between June 2014 and July 2015 in Melbourne, Australia. Data were thematically analysed. RESULTS: Participants agreed that hand hygiene practice was important in reducing disease transmissions. However, barriers such as variations of hand hygiene habits, relating visibility to transmission; concerns around young children being obsessed with washing hands; children already being ‘too clean’ and the need to build their immunity through exposure to dirt; and scepticism that hand hygiene practice was achievable in young children, all hindered participants’ motivation to develop good hand hygiene behaviour in young children. CONCLUSION: Despite the established benefits of hand hygiene, sustained efforts are needed to ensure its uptake in routine care. To overcome the barriers identified in this study a multifaceted intervention is needed that includes teaching young children good hand hygiene habits, PCPs prompting parents and young children to practice hand hygiene when coming for an RTI consultation, reassuring parents that effective hand hygiene practice will not lead to abnormal psychological behaviour in their children, and community health promotion education campaigns.",2019 Apr 11,"['Biezen, Ruby', 'Grando, Danilla', 'Mazza, Danielle', 'Brijnath, Bianca']",BMC Public Health,,,True
936a08054b4018e58ae70402e8918715904451ad,PMC,Molecular characterization of pathogenic 4/91-like and QX-like infectious bronchitis virus infecting commercial poultry farms in Indonesia,http://dx.doi.org/10.14202/vetworld.2019.277-287,PMC6460877,31040571,CC BY,"BACKGROUND AND AIM: Existing data on the characteristics of infectious bronchitis virus (IBV) gathered throughout Indonesia have been recognized to indicate variants similar to globally distributed vaccine strains. Despite past and current intensive vaccination programs, IBV infections in the country’s poultry industry have not been effectively controlled. Therefore, this study aimed to investigate the genotype of several isolates based on partial S1 gene sequences. In particular, the investigation is directed to focus on layer chickens in actively vaccinated farms indicating IBV symptoms. MATERIALS AND METHODS: Samples were isolated from ten different layer chicken flocks experiencing respiratory problem, drops in egg production, and a “penguin-like” stance, which were collected from commercial poultry farms in Central Java and Yogyakarta regions, Indonesia, within the periods of 2012-2018. Fragment of the S1 gene of IBV sampled from actively vaccinated commercial poultry farms was amplified using primer 5’-aca tgg taa ttt ttc aga tgg-3’ (forward) and 5’-cag att gct tac aac cac c-3’ (reverse) with the length of polymerase chain reaction (PCR) product at 383 bp. The sequence of samples was then compared with the sequence of reference S1 gene nucleotides of IBV from NCBI GenBank database. The amino acid analysis and multiple alignment sequence were conducted using Mega X. RESULTS: During necropsy, enlargement of the oviduct and swollen kidney were observed. Reverse transcription-PCR diagnosis of their 383 bp S1 gene showed that all samples were IBV positive. Phylogenetic analysis of the S1 gene discovered seven samples to be clustered as 4/91-like strains. Meanwhile, the remaining three samples were grouped in QX-like strain cluster. CONCLUSION: This study is a pioneering report providing molecular evidence of pathogenic QX-like and 4/91-like strains circulating in Indonesia. Findings discovered, in this study, strongly suggested the importance of improving protections by available IBV vaccines through updated circulating strain clusters. It is critical to ensure the delivery of an effective control measurement of and vaccination protocols against IBV infections in the country’s commercial poultry industry in particular and worldwide in general.",2019 Feb 20,"['Wibowo, Michael H.', 'Ginting, Teridah E.', 'Asmara, Widya']",Vet World,,,True
3cba082e1f0b91d9143ea8e72eada78be0474064,PMC,Coinfection of diarrheagenic bacterial and viral pathogens in piglets of Northeast region of India,http://dx.doi.org/10.14202/vetworld.2019.224-230,PMC6460878,31040562,CC BY,"AIM: This study aimed to study the prevalence of the coinfection of enteric bacterial and viral pathogens, namely Escherichia coli, Salmonella, Rotavirus, and Picobirnavirus from fecal samples of pre-weaned piglets in Northeast region of India. MATERIALS AND METHODS: A total of 457 fresh fecal samples were collected from piglets under 9 weeks old during 2013-2015 from organized (n=225) and unorganized (n=232) farms of Manipur, Meghalaya, Mizoram, and Nagaland. Samples were collected from diarrheic (n =339) and non-diarrheic (n=118) piglets including local indigenous (n=130) and crossbreed (n=327) piglets in different seasons during the study period. The samples were processed for the isolation of E. coli and Salmonella and detection of their putative virulence genes by polymerase chain reaction (PCR). Samples were also processed for the detection of Rotavirus and Picobirnavirus by RNA-polyacrylamide agarose gel electrophoresis and reverse transcriptase-PCR (RT-PCR). RESULTS: A total of 11 (2.40%) samples were found positive for two or more coinfecting enteric bacterial and viral pathogens. All the 11 positive fecal samples were recovered from diarrheic piglets. Salmonella Typhimurium (enterotoxin, stn gene) and Picobirnavirus genogroup 1 were found to be more frequent as coinfecting agents. Coinfection was recorded higher in unorganized (3.87%) compared to organized farm (0.88%). Again, higher detection was recorded in crossbreed (2.75%) than local indigenous piglets (1.53%). The occurrence of coinfection was found to be more common during summer (4.68%) followed by winter (2.27%) season. CONCLUSION: The present study highlighted the significance of E. coli, Salmonella, Rotavirus, and Picobirnavirus as important diarrheagenic pathogens causing coinfection in piglets in Northeast region of India. Probably, this is the first systematic study of the coinfection of four important diarrheagenic bacterial and viral agents associated with piglet diarrhea in India.",2019 Feb 9,"['Kylla, Hosterson', 'Dutta, Tapan K.', 'Roychoudhury, Parimal', 'Subudhi, Prasant K.']",Vet World,,,True
403be352ce64603bdb313a00238d5b77b7305321,PMC,"Genetic characterization of S1 gene of infectious bronchitis virus isolated from commercial poultry flocks in West Java, Indonesia",http://dx.doi.org/10.14202/vetworld.2019.231-235,PMC6460881,31040563,CC BY,"BACKGROUND AND AIM: Infectious bronchitis (IB) is still a major problem among poultry industry in Indonesia, IB outbreaks continue to happen even in vaccinated flocks. The emergence of new IB virus (IBV) variants might lead to mismatching between vaccine virus strain and circulating virus strain, this may be a reason of vaccination failure. Information about circulating IBV in a region is important to decide which IB vaccine should be used. However, information about recent IBV strains which circulated in Indonesia and their genetic characters were limited; therefore, the aim of our research was to determine the genetic characterization of S1 gene of IBV isolated from commercial poultry flocks in West Java, Indonesia. MATERIALS AND METHODS: A total of 47 viral isolate samples collected from chickens with clinical sign and reduced in egg production. Six IB live vaccines were used as control, the reference vaccines represent IBV strains including H120, H52, 4/91, CR88, 233A, and 1-96. Primers XCe2+ and XCe2- were used to amplify S1 gene partially. RESULTS: Twenty-six of 47 samples showed positive result to S1 gene of IBV by reverse transcription-polymerase chain reaction. Three IBV isolates, Indonesia/K233A31/18, Indonesia/K4A9/17, and Indonesia/P3/17, were selected for nucleotide sequencing. Phylogenetic analysis of 352 nucleotides of the partial S1 gene shows that isolates Indonesia/K4A9/17 and Indonesia/K233A31/18 have 100% homology with IBV vaccine strain 4/91, while isolate Indonesia/P3/17 has 100% homology with IBV vaccine strain 233A. CONCLUSION: Our result indicates that at least two IBV strains were circulating among poultry in West Java, Indonesia, which is IBV close to vaccine strain 4/91 and 233A. The present study provides updates on the circulating IBV in commercial poultry flocks in West Java, Indonesia, and might use as guidance on selecting a proper IB vaccine strain to improve IB vaccination efficacy in certain region.",2019 Feb 11,"['Setiawaty, Rahajeng', 'Soejoedono, Retno Damajanti', 'Poetri, Okti Nadia']",Vet World,,,True
c0713cd16ef0d30221483b314837bcf9e642a884,PMC,The Gut Microbiota-Host Partnership as a Potential Driver of Kawasaki Syndrome,http://dx.doi.org/10.3389/fped.2019.00124,PMC6460951,31024869,CC BY,"Kawasaki syndrome (KS) is a necrotizing vasculitis of small- and medium-sized vessels mostly affecting children under 5 years of age; a host of clinical and epidemiological data supports the notion that KS might result from an infectious disease. However, many efforts have failed to identify a potentially universal trigger of KS. The contribution of the intestinal microbial community—called the “microbiota”—to KS has been evaluated by an increasing number of studies, though limited to small cohorts of patients. Differences in the microbiota composition were found in children with KS, both its acute and non-acute phase, with abnormal colonization by Streptococcus species in the intestinal tract and a wider presence of Gram-positive cocci in jejunal biopsies. In particular, a higher number of Gram-positive cocci (of the genera Streptococcus and Staphylococcus), Eubacterium, Peptostreptococcus, and HSP60-producing Gram-negative microbes have been found in the stools of KS children, and their effects on the antigenic repertoire of specific T cells and Vβ2 T cell expansion have been assessed. Conversely, Lactobacilli were lacking in most children with KS compared with other febrile illnesses and healthy controls. All studies available to date have confirmed that an imbalance in the gut microbiota might indirectly interfere with the normal function of innate and adaptive immunity, and that variable microbiota interactions with environmental factors, mainly infectious agents, might selectively drive the development of KS in genetically susceptible children. Further investigations of the intestinal microflora in larger cohorts of KS patients will provide clues to disentangle the pathogenesis of this disease and probably indicate disease-modifying agents or more rational KS-specific therapies.",2019 Apr 5,"['Esposito, Susanna', 'Polinori, Ilaria', 'Rigante, Donato']",Front Pediatr,,,True
fa1d2145aa1af1e5232d8d425f36f4e9bb20f392,PMC,"Respiratory syncytial virus, human metapneumovirus, and influenza virus infection in Bangkok, 2016-2017",http://dx.doi.org/10.7717/peerj.6748,PMC6462397,30997293,CC BY,"Children and adults residing in densely populated urban centers around the world are at risk of seasonal influenza-like illness caused by respiratory viruses such as influenza virus, human metapneumovirus (hMPV), and respiratory syncytial virus (RSV). In a large metropolitan of Thailand’s capital city Bangkok, most respiratory infections are rarely confirmed by molecular diagnostics. We therefore examined the frequency of RSV, hMPV, and influenza virus in 8,842 patients who presented influenza-like illness and sought medical care at a large hospital in Bangkok between 2016 and 2017. Using a multiplex real-time reverse-transcription polymerase chain reaction (RT-PCR), 30.5% (2,699/8,842) of nasopharyngeal (NP) swab samples tested positive for one or more of these viruses. Influenza virus comprised 17.3% (1,528/8,842), of which the majority were influenza A/H3N2. Such infection was most prevalent among adults and the elderly. RSV was identified in 11.4% (1,011/8,842) and were mostly ON1 and BA9 genotypes. Of the hMPV-positive samples (3.6%, 318/8,842), genotypes A2, B1, and B2 were detected. A small number of individuals experienced co-infections (1.8%, 155/8,842), most commonly between RSV and influenza A/H3N2. RSV and hMPV co-infections were also found, but mainly in young children. Viral respiratory tract infection peaked locally in the rainy season (June to September). These findings support the utility of rapid nucleic acid testing of RSV, hMPV, and influenza virus in patients with ILI.",2019 Apr 11,"['Thongpan, Ilada', 'Suntronwong, Nungruthai', 'Vichaiwattana, Preeyaporn', 'Wanlapakorn, Nasamon', 'Vongpunsawad, Sompong', 'Poovorawan, Yong']",PeerJ,,,True
37a69d36617af76ae26d7801efb776af8f7488a9,PMC,Zika Outbreak Emergency Preparedness and Response of Malaysian Private Healthcare Professionals: Are They Ready?,http://dx.doi.org/10.3390/microorganisms7030087,PMC6462960,30893885,CC BY,"Zika virus has been declared as a public health emergency of international concern. The Center for Disease Control and Prevention has issued guidelines reminding healthcare workers about the importance of taking steps to prevent the spread of Zika virus, how to test and isolate patients suspected of carrying the Zika virus, and how to protect themselves from infection. Therefore, it is of utmost importance for healthcare professionals to be fully aware of Zika virus preparedness, and response measures should an outbreak occur in Malaysia in order to quickly and efficiently contain the outbreak, ensure the safety of individual or healthcare personnel safety, as well as to prevent further spreading of the disease. This research aims to show how prepared Malaysian healthcare professionals are against Zika virus and how well can they respond during an outbreak. In total, 504 healthcare professionals (128 general practitioners, 215 community pharmacists, 161 nurses) from private health clinics were the target population of the four states of Malaysia where Zika cases suspected. The sample size of each category was calculated by using a formula for estimating the population proportion. An additional 10% of the calculated sample size was added to compensate the non-response rate. The Center For Disease Control and Prevention and World Health Organisation provided a checklist to assess how prepared healthcare professionals are for an Zika outbreak. This checklist was modified to a questionnaire in order to assess health care professionals’ preparedness and response to the Zika outbreak. Community pharmacists are still lacking in their preparedness and perceived response to the Zika outbreak compared to the general practitioners in the private sector. Hence community pharmacists should attend training given by the Ministry of Health Malaysia as a continuing education, which may help them to respond during a Zika outbreak.",2019 Mar 19,"['Rajiah, Kingston', 'Maharajan, Mari Kannan', 'Yin, Pua Yin', 'Yee, Yap Wei', 'Lin, Wong Wan', 'Kean, Chew Hui']",Microorganisms,,,True
d897dfae4f3b4d98b4bb6fde108a29c253d87e50,PMC,Slicing and dicing viruses: antiviral RNA interference in mammals,http://dx.doi.org/10.15252/embj.2018100941,PMC6463209,30872283,CC BY,"To protect against the harmful consequences of viral infections, organisms are equipped with sophisticated antiviral mechanisms, including cell‐intrinsic means to restrict viral replication and propagation. Plant and invertebrate cells utilise mostly RNA interference (RNAi), an RNA‐based mechanism, for cell‐intrinsic immunity to viruses while vertebrates rely on the protein‐based interferon (IFN)‐driven innate immune system for the same purpose. The RNAi machinery is conserved in vertebrate cells, yet whether antiviral RNAi is still active in mammals and functionally relevant to mammalian antiviral defence is intensely debated. Here, we discuss cellular and viral factors that impact on antiviral RNAi and the contexts in which this system might be at play in mammalian resistance to viral infection.",2019 Apr 15,"['Maillard, Pierre V', 'van der Veen, Annemarthe G', 'Poirier, Enzo Z', 'Reis e Sousa, Caetano']",EMBO J,,,True
cd59245a431a62e93a213ec343f168d77dcfc199,PMC,Cathepsin L promotes secretory IgA response by participating in antigen presentation pathways during Mycoplasma Hyopneumoniae infection,http://dx.doi.org/10.1371/journal.pone.0215408,PMC6464228,30986254,CC BY,"Cathepsin L (CTSL) has been proved to help contain leishmaniasis and mycoplasma infection in mice by supporting cellular immune responses, but the regulatory functions of CTSL on mucosal immune responses haven’t been tested and remain undefined. Here, we investigated the effects of CTSL on SIgA responses and invariant chain (Ii) degradations in the co-cultured swine dendritic cells (DCs) and B cells system in vitro. When the cells system were transfected with vector CTSL-GFP or incubated with recombinant CTSL (rCTSL) before they were infected with Mycoplasma hyopneumoniae (M.hp), SIgA significantly increased and Ii chain was degraded into smaller intermediates, while SIgA decreased when CTSL was knockdown or inhibited with E64. To confirm the SIgA responses promoted by CTSL contribute to the resistance to mycoplasma pneumonia, pigs injected with rCTSL before they were challenged with M.hp, showed milder clinical symptoms and histopathological damage of lungs, less mycoplasma burden together with higher secretion of SIgA, percentages of CD4(+) T cells and level of MHC II molecules comparing with the group without rCTSL. Collectively, these results suggested that rCTSL could provide effective protection for piglets against mycoplasma pneumonia by enhancing M.hp-specific mucosal immune responses through its role in antigen presentation by processing the invariant chain.",2019 Apr 15,"['Zhang, Ning', 'Gao, Peng', 'Yin, Bao', 'Li, Jiahe', 'Wu, Tong', 'Kuang, Yu', 'Wu, Wenxue', 'Li, Jinxiang']",PLoS One,,,True
67282d82fcba34faf696a510ca4d54b8804289cd,PMC,Development of a Phage Display Panning Strategy Utilizing Crude Antigens: Isolation of MERS-CoV Nucleoprotein human antibodies,http://dx.doi.org/10.1038/s41598-019-42628-6,PMC6465254,30988390,CC BY,"Antibody phage display has been pivotal in the quest to generate human monoclonal antibodies for biomedical and research applications. Target antigen preparation is a main bottleneck associated with the panning process. This includes production complexity, downstream purification, quality and yield. In many instances, purified antigens are preferred for panning but this may not be possible for certain difficult target antigens. Here, we describe an improved procedure of affinity selection against crude or non-purified antigen by saturation of non-binders with blocking agents to promote positive binder enrichment termed as Yin-Yang panning. A naïve human scFv library with kappa light chain repertoire with a library size of 10(9) was developed. The improved Yin-Yang biopanning process was able to enrich monoclonal antibodies specific to the MERS-CoV nucleoprotein. Three unique monoclonal antibodies were isolated in the process. The Yin-Yang biopanning method highlights the possibility of utilizing crude antigens for the isolation of monoclonal antibodies by phage display.",2019 Apr 15,"['Lim, Chia Chiu', 'Woo, Patrick C. Y.', 'Lim, Theam Soon']",Sci Rep,,,True
0abbc904e7a1b2e1c3ea7be75ee2a61931e0a941,PMC,Automated cell-based luminescence assay for profiling antiviral compound activity against enteroviruses,http://dx.doi.org/10.1038/s41598-019-42160-7,PMC6465263,30988314,CC BY,"We describe the development, optimisation, and validation of an automated, cell-based and high-throughput screening assay using existing luminescence-based ATPlite reagents for identifying antiviral compounds that inhibit enterovirus replication. Antiviral efficacy was determined by measuring the ATP levels in cells that were protected from the viral cytopathic effect (CPE) by the antiviral compounds pleconaril and rupintrivir. CPE-based assay conditions were optimised at a cell density of 5000 cells/well and a viral infection dose of 100 CCID(50) in 384-well plates. The assay exhibited excellent robustness, with Z′-factor values between 0.75 and 0.82, coefficients of variation between 0.33% and 1.45%, and signal-to-background ratios ranging from 6.92 to 22.6 when testing three enterovirus A71 isolates circulating in China. The assay was also suitable for screening other picornaviruses, such as poliovirus, coxsackievirus, echovirus, and parechovirus.",2019 Apr 15,"['Zhang, Mingyu', 'Zhang, Yong', 'Wang, Yan', 'Lv, Wanyu', 'Zhang, Yanyang']",Sci Rep,,,True
22a58b64c7dfabae525a81e1d12a4e4ff70c1fa2,PMC,"Upsurge of Enterovirus D68 and Circulation of the New Subclade D3 and Subclade B3 in Beijing, China, 2016",http://dx.doi.org/10.1038/s41598-019-42651-7,PMC6465342,30988475,CC BY,"We conducted a surveillance among acute respiratory tract infection (ARTI) cases to define the epidemiology, clinical characteristics and genetic variations of enterovirus D68 (EV-D68) in Beijing, China from 2015 to 2017. Nasopharyngeal swabs and sputum were collected from 30 sentinel hospitals in Beijing and subjected to EV and EV-D68 detection by real-time PCR. The VP1 gene region and complete genome sequences of EV-D68 positive cases were analyzed. Of 21816 ARTI cases, 619 (2.84%) were EV positive and 42 cases were EV-D68 positive. The detection rates of EV-D68 were 0 (0/6644) in 2015, 0.53% (40/7522) in 2016 and 0.03% (2/7650) in 2017, respectively. Two peaks of EV-D68 infections occurred in late summer and early-winter. Ten cases (23.81%) with upper respiratory tract infection and 32 cases (76.19%) presented with pneumonia, including 3 cases with severe pneumonia. The phylogenetic analysis suggested 15 subclade D3 strains and 27 subclade B3 strains of EV-D68 were circulated in China from 2016 to 2017. A total of 52 amino acid polymorphisms were identified between subclades D1 and D3. These data suggest an upsurge of EV-D68 occurred in Beijing in 2016, the new subclade D3 emerged in 2016 and co-circulated with subclade B3 between 2016 and 2017.",2019 Apr 15,"['Shen, Lingyu', 'Gong, Cheng', 'Xiang, Zichun', 'Zhang, Tiegang', 'Li, Maozhong', 'Li, Aihua', 'Luo, Ming', 'Huang, Fang']",Sci Rep,,,False
85544c40199592db3f81823f341f19f303fef7ec,PMC,"Upsurge of Enterovirus D68 and Circulation of the New Subclade D3 and Subclade B3 in Beijing, China, 2016",http://dx.doi.org/10.1038/s41598-019-42651-7,PMC6465342,30988475,CC BY,"We conducted a surveillance among acute respiratory tract infection (ARTI) cases to define the epidemiology, clinical characteristics and genetic variations of enterovirus D68 (EV-D68) in Beijing, China from 2015 to 2017. Nasopharyngeal swabs and sputum were collected from 30 sentinel hospitals in Beijing and subjected to EV and EV-D68 detection by real-time PCR. The VP1 gene region and complete genome sequences of EV-D68 positive cases were analyzed. Of 21816 ARTI cases, 619 (2.84%) were EV positive and 42 cases were EV-D68 positive. The detection rates of EV-D68 were 0 (0/6644) in 2015, 0.53% (40/7522) in 2016 and 0.03% (2/7650) in 2017, respectively. Two peaks of EV-D68 infections occurred in late summer and early-winter. Ten cases (23.81%) with upper respiratory tract infection and 32 cases (76.19%) presented with pneumonia, including 3 cases with severe pneumonia. The phylogenetic analysis suggested 15 subclade D3 strains and 27 subclade B3 strains of EV-D68 were circulated in China from 2016 to 2017. A total of 52 amino acid polymorphisms were identified between subclades D1 and D3. These data suggest an upsurge of EV-D68 occurred in Beijing in 2016, the new subclade D3 emerged in 2016 and co-circulated with subclade B3 between 2016 and 2017.",2019 Apr 15,"['Shen, Lingyu', 'Gong, Cheng', 'Xiang, Zichun', 'Zhang, Tiegang', 'Li, Maozhong', 'Li, Aihua', 'Luo, Ming', 'Huang, Fang']",Sci Rep,,,True
d0b5d5ddc6b64721d23c64bf1dcd26d85b75d326,PMC,Rabies-based vaccine induces potent immune responses against Nipah virus,http://dx.doi.org/10.1038/s41541-019-0109-5,PMC6465360,31016033,CC BY,"Nipah Virus (NiV) is a re-emerging zoonotic pathogen in the genus Henipavirus of the Paramyxoviridae family of viruses. NiV is endemic to Bangladesh and Malaysia and is highly fatal to both livestock and humans (human case fatality rate = 74.5%). Currently, there is no approved vaccine against NiV on the market. The goal of this study was to use a recombinant RABV vector expressing NiV glycoprotein (NiV G) to develop a bivalent candidate vaccine against NiV disease and rabies virus (RABV) disease, which is also a significant health burden in the regions where NiV is endemic. The rabies vector is a well-established vaccine strain that lacks neurovirulence and can stably expresses foreign antigens that are immunogenic in various animal models. Mice inoculated intranasally with the live recombinant RABV/NiV vaccine (NIPARAB) showed no signs of disease. To test the immunogenicity of the vaccine candidate, groups of C57BL/6 mice were immunized intramuscularly with a single dose of live vaccine particles or two doses of chemically inactivated viral particles. Both vaccination groups showed NiV G-specific seroconversion, and the inactivated (INAC) vaccine group yielded higher titers of NiV G-specific antibodies. Furthermore, cross-reactivity of NiV G-specific immune sera against Hendra virus (HeV), was confirmed by immunofluorescence (IF) and indirect ELISA against soluble recombinant HeV glycoprotein (HeV G). Both live and killed vaccines induced neutralizing antibodies. These results indicate that NIPARAB may be used as a killed virus vaccine to protect humans against NiV and RABV, and possibly as a preventative measure against HeV as well.",2019 Apr 15,"['Keshwara, Rohan', 'Shiels, Thomas', 'Postnikova, Elena', 'Kurup, Drishya', 'Wirblich, Christoph', 'Johnson, Reed F.', 'Schnell, Matthias J.']",NPJ Vaccines,,,False
02753048c4dc699d155288935b9dc6517a79f279,PMC,Rabies-based vaccine induces potent immune responses against Nipah virus,http://dx.doi.org/10.1038/s41541-019-0109-5,PMC6465360,31016033,CC BY,"Nipah Virus (NiV) is a re-emerging zoonotic pathogen in the genus Henipavirus of the Paramyxoviridae family of viruses. NiV is endemic to Bangladesh and Malaysia and is highly fatal to both livestock and humans (human case fatality rate = 74.5%). Currently, there is no approved vaccine against NiV on the market. The goal of this study was to use a recombinant RABV vector expressing NiV glycoprotein (NiV G) to develop a bivalent candidate vaccine against NiV disease and rabies virus (RABV) disease, which is also a significant health burden in the regions where NiV is endemic. The rabies vector is a well-established vaccine strain that lacks neurovirulence and can stably expresses foreign antigens that are immunogenic in various animal models. Mice inoculated intranasally with the live recombinant RABV/NiV vaccine (NIPARAB) showed no signs of disease. To test the immunogenicity of the vaccine candidate, groups of C57BL/6 mice were immunized intramuscularly with a single dose of live vaccine particles or two doses of chemically inactivated viral particles. Both vaccination groups showed NiV G-specific seroconversion, and the inactivated (INAC) vaccine group yielded higher titers of NiV G-specific antibodies. Furthermore, cross-reactivity of NiV G-specific immune sera against Hendra virus (HeV), was confirmed by immunofluorescence (IF) and indirect ELISA against soluble recombinant HeV glycoprotein (HeV G). Both live and killed vaccines induced neutralizing antibodies. These results indicate that NIPARAB may be used as a killed virus vaccine to protect humans against NiV and RABV, and possibly as a preventative measure against HeV as well.",2019 Apr 15,"['Keshwara, Rohan', 'Shiels, Thomas', 'Postnikova, Elena', 'Kurup, Drishya', 'Wirblich, Christoph', 'Johnson, Reed F.', 'Schnell, Matthias J.']",NPJ Vaccines,,,True
8cff063c436820e2c85479244dcf7b5f123d4446,PMC,A Novel Approach to Clustering Genome Sequences Using Inter-nucleotide Covariance,http://dx.doi.org/10.3389/fgene.2019.00234,PMC6465635,31024610,CC BY,"Classification of DNA sequences is an important issue in the bioinformatics study, yet most existing methods for phylogenetic analysis including Multiple Sequence Alignment (MSA) are time-consuming and computationally expensive. The alignment-free methods are popular nowadays, whereas the manual intervention in those methods usually decreases the accuracy. Also, the interactions among nucleotides are neglected in most methods. Here we propose a new Accumulated Natural Vector (ANV) method which represents each DNA sequence by a point in ℝ(18). By calculating the Accumulated Indicator Functions of nucleotides, we can further find an Accumulated Natural Vector for each sequence. This new Accumulated Natural Vector not only can capture the distribution of each nucleotide, but also provide the covariance among nucleotides. Thus global comparison of DNA sequences or genomes can be done easily in ℝ(18). The tests of ANV of datasets of different sizes and types have proved the accuracy and time-efficiency of the new proposed ANV method.",2019 Apr 9,"['Dong, Rui', 'He, Lily', 'He, Rong Lucy', 'Yau, Stephen S.-T.']",Front Genet,,,True
6d021f582f338ea0a0e9a61e6a4e76df73287b1d,PMC,Therapeutic Synergy Between Antibiotics and Pulmonary Toll-Like Receptor 5 Stimulation in Antibiotic-Sensitive or -Resistant Pneumonia,http://dx.doi.org/10.3389/fimmu.2019.00723,PMC6465676,31024555,CC BY,"Bacterial infections of the respiratory tract constitute a major cause of death worldwide. Given the constant rise in bacterial resistance to antibiotics, treatment failure is increasingly frequent. In this context, innovative therapeutic strategies are urgently needed. Stimulation of innate immune cells in the respiratory tract [via activation of Toll-like receptors (TLRs)] is an attractive approach for rapidly activating the body's immune defenses against a broad spectrum of microorganisms. Previous studies of the TLR5 agonist flagellin in animal models showed that standalone TLR stimulation does not result in the effective treatment of pneumococcal respiratory infection but does significantly improve the therapeutic outcome of concomitant antibiotic treatment. Here, we investigated the antibacterial interaction between antibiotic and intranasal flagellin in a mouse model of pneumococcal respiratory infection. Using various doses of orally administered amoxicillin or systemically administered cotrimoxazole, we found that the intranasal instillation of flagellin (a dose that promotes maximal lung pro-inflammatory responses) induces synergistic rather than additive antibacterial effects against antibiotic–susceptible pneumococcus. We next set up a model of infection with pneumococcus that is resistant to multiple antibiotics in the context of influenza superinfection. Remarkably, the combination of amoxicillin and flagellin effectively treated superinfection with the amoxicillin-resistant pneumococcus since the bacterial clearance was increased by more than 100-fold compared to standalone treatments. Our results also showed that, in response to flagellin, the lung tissue generated an innate immune response even though it had been damaged by the influenza virus and pneumococcal infections. In conclusion, we demonstrated that the selective boosting of lung innate immunity is a conceptually advantageous approach for improving the effectiveness of antibiotic treatment and fighting antibiotic-resistant bacteria.",2019 Apr 9,"['Matarazzo, Laura', 'Casilag, Fiordiligie', 'Porte, Rémi', 'Wallet, Frederic', 'Cayet, Delphine', 'Faveeuw, Christelle', 'Carnoy, Christophe', 'Sirard, Jean-Claude']",Front Immunol,,,True
1a19bed3bfcb373626804c55b111ca79e812efd1,PMC,Construction and Immunogenicity of Novel Chimeric Virus-Like Particles Bearing Antigens of Infectious Bronchitis Virus and Newcastle Disease Virus,http://dx.doi.org/10.3390/v11030254,PMC6465995,30871190,CC BY,"Infectious bronchitis virus (IBV) and Newcastle disease virus (NDV) are two poultry pathogens seriously affecting the poultry industry. Here, IBV S1 and the ectodomain of NDV F proteins were separately linked with the trans-membrane and carboxy-terminal domain of IBV S protein (S(TMCT)), composing rS and rF; thus, a novel chimeric infectious bronchitis-Newcastle disease (IB-ND) virus-like particles (VLPs) vaccine containing the rS, rF, and IBV M protein was constructed. Under the transmission electron microscope (TEM), VLPs possessing similar morphology to natural IBV were observed. To evaluate the immunogenicity of chimeric IB-ND VLPs, specific pathogen-free (SPF) chickens were immunized with three increasing doses (50, 75, and 100 μg protein of VLPs). Results of ELISAs detecting IBV and NDV specific antibodies and IL-4 and IFN-γ T cell cytokines indicated that vaccination with chimeric IB-ND VLPs could efficiently induce humoral and cellular immune responses. In the challenge study, chimeric IB-ND VLPs (100 μg protein) provided 100% protection against IBV or NDV virulent challenge from death, and viral RNA levels in tissues and swabs were greatly reduced. Collectively, chimeric IB-ND VLPs are highly immunogenic and could provide complete protection from an IBV or NDV virulent challenge. Chimeric IB-ND VLPs are an appealing vaccine candidate and a promising vaccine platform bearing multivalent antigens.",2019 Mar 13,"['Wu, Xuan', 'Zhai, Xiwen', 'Lai, Yan', 'Zuo, Lei', 'Zhang, Yu', 'Mei, Xueran', 'Xiang, Rong', 'Kang, Zhuangzhuang', 'Zhou, Long', 'Wang, Hongning']",Viruses,,,True
169ca2aef2c810471d33aa6522aa25a70594ae26,PMC,Innate Immune Responses to Avian Influenza Viruses in Ducks and Chickens,http://dx.doi.org/10.3390/vetsci6010005,PMC6466002,30634569,CC BY,"Mallard ducks are important natural hosts of low pathogenic avian influenza (LPAI) viruses and many strains circulate in this reservoir and cause little harm. Some strains can be transmitted to other hosts, including chickens, and cause respiratory and systemic disease. Rarely, these highly pathogenic avian influenza (HPAI) viruses cause disease in mallards, while chickens are highly susceptible. The long co-evolution of mallard ducks with influenza viruses has undoubtedly fine-tuned many immunological host–pathogen interactions to confer resistance to disease, which are poorly understood. Here, we compare innate responses to different avian influenza viruses in ducks and chickens to reveal differences that point to potential mechanisms of disease resistance. Mallard ducks are permissive to LPAI replication in their intestinal tissues without overtly compromising their fitness. In contrast, the mallard response to HPAI infection reflects an immediate and robust induction of type I interferon and antiviral interferon stimulated genes, highlighting the importance of the RIG-I pathway. Ducks also appear to limit the duration of the response, particularly of pro-inflammatory cytokine expression. Chickens lack RIG-I, and some modulators of the signaling pathway and may be compromised in initiating an early interferon response, allowing more viral replication and consequent damage. We review current knowledge about innate response mediators to influenza infection in mallard ducks compared to chickens to gain insight into protective immune responses, and open questions for future research.",2019 Jan 10,"['Evseev, Danyel', 'Magor, Katharine E.']",Vet Sci,,,True
8b61716032c98b87bbc4276d9fcec91025574467,PMC,Enhanced Autophagy Contributes to Reduced Viral Infection in Black Flying Fox Cells,http://dx.doi.org/10.3390/v11030260,PMC6466025,30875748,CC BY,"Bats are increasingly implicated as hosts of highly pathogenic viruses. The underlying virus–host interactions and cellular mechanisms that promote co-existence remain ill-defined, but physiological traits such as flight and longevity are proposed to drive these adaptations. Autophagy is a cellular homeostatic process that regulates ageing, metabolism, and intrinsic immune defense. We quantified basal and stimulated autophagic responses in black flying fox cells, and demonstrated that although black flying fox cells are susceptible to Australian bat lyssavirus (ABLV) infection, viral replication is dampened in these bat cells. Black flying fox cells tolerated prolonged ABLV infection with less cell death relative to comparable human cells, suggesting post-entry mechanisms interference with virus replication. An elevated basal autophagic level was observed and autophagy was induced in response to high virus doses. Pharmacological stimulation of the autophagy pathway reduced virus replication, indicating autophagy acts as an anti-viral mechanism. Enhancement of basal and virus-induced autophagy in bat cells connects related reports that long-lived species possess homeostatic processes that dampen oxidative stress and macromolecule damage. Exemplifying the potential that evolved cellular homeostatic adaptations like autophagy may secondarily act as anti-viral mechanisms, enabling bats to serve as natural hosts to an assortment of pathogenic viruses. Furthermore, our data suggest autophagy-inducing drugs may provide a novel therapeutic strategy for combating lyssavirus infection.",2019 Mar 14,"['Laing, Eric D.', 'Sterling, Spencer L.', 'Weir, Dawn L.', 'Beauregard, Chelsi R.', 'Smith, Ina L.', 'Larsen, Sasha E.', 'Wang, Lin-Fa', 'Snow, Andrew L.', 'Schaefer, Brian C.', 'Broder, Christopher C.']",Viruses,,,True
040c9714be80e4a337f6737d17e94171c25cc076,PMC,Characterization of the Filovirus-Resistant Cell Line SH-SY5Y Reveals Redundant Role of Cell Surface Entry Factors,http://dx.doi.org/10.3390/v11030275,PMC6466046,30893855,CC BY,"Filoviruses infect a wide range of cell types with the exception of lymphocytes. The intracellular proteins cathepsin B and L, two-pore channel 1 and 2, and bona fide receptor Niemann–Pick Disease C1 (NPC1) are essential for the endosomal phase of cell entry. However, earlier steps of filoviral infection remain poorly characterized. Numerous plasma membrane proteins have been implicated in attachment but it is still unclear which ones are sufficient for productive entry. To define a minimal set of host factors required for filoviral glycoprotein-driven cell entry, we screened twelve cell lines and identified the nonlymphocytic cell line SH-SY5Y to be specifically resistant to filovirus infection. Heterokaryons of SH-SY5Y cells fused to susceptible cells were susceptible to filoviruses, indicating that SH-SY5Y cells do not express a restriction factor but lack an enabling factor critical for filovirus entry. However, all tested cell lines expressed functional intracellular factors. Global gene expression profiling of known cell surface entry factors and protein expression levels of analyzed attachment factors did not reveal any correlation between susceptibility and expression of a specific host factor. Using binding assays with recombinant filovirus glycoprotein, we identified cell attachment as the step impaired in filovirus entry in SH-SY5Y cells. Individual overexpression of attachment factors T-cell immunoglobulin and mucin domain 1 (TIM-1), Axl, Mer, or dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) rendered SH-SY5Y cells susceptible to filovirus glycoprotein-driven transduction. Our study reveals that a lack of attachment factors limits filovirus entry and provides direct experimental support for a model of filoviral cell attachment where host factor usage at the cell surface is highly promiscuous.",2019 Mar 19,"['Zapatero-Belinchón, Francisco J.', 'Dietzel, Erik', 'Dolnik, Olga', 'Döhner, Katinka', 'Costa, Rui', 'Hertel, Barbara', 'Veselkova, Barbora', 'Kirui, Jared', 'Klintworth, Anneke', 'Manns, Michael P.', 'Pöhlmann, Stefan', 'Pietschmann, Thomas', 'Krey, Thomas', 'Ciesek, Sandra', 'Gerold, Gisa', 'Sodeik, Beate', 'Becker, Stephan', 'von Hahn, Thomas']",Viruses,,,True
a9389c989b9ce63db440a8c6a8baed8f38ad8638,PMC,Characterization of the Filovirus-Resistant Cell Line SH-SY5Y Reveals Redundant Role of Cell Surface Entry Factors,http://dx.doi.org/10.3390/v11030275,PMC6466046,30893855,CC BY,"Filoviruses infect a wide range of cell types with the exception of lymphocytes. The intracellular proteins cathepsin B and L, two-pore channel 1 and 2, and bona fide receptor Niemann–Pick Disease C1 (NPC1) are essential for the endosomal phase of cell entry. However, earlier steps of filoviral infection remain poorly characterized. Numerous plasma membrane proteins have been implicated in attachment but it is still unclear which ones are sufficient for productive entry. To define a minimal set of host factors required for filoviral glycoprotein-driven cell entry, we screened twelve cell lines and identified the nonlymphocytic cell line SH-SY5Y to be specifically resistant to filovirus infection. Heterokaryons of SH-SY5Y cells fused to susceptible cells were susceptible to filoviruses, indicating that SH-SY5Y cells do not express a restriction factor but lack an enabling factor critical for filovirus entry. However, all tested cell lines expressed functional intracellular factors. Global gene expression profiling of known cell surface entry factors and protein expression levels of analyzed attachment factors did not reveal any correlation between susceptibility and expression of a specific host factor. Using binding assays with recombinant filovirus glycoprotein, we identified cell attachment as the step impaired in filovirus entry in SH-SY5Y cells. Individual overexpression of attachment factors T-cell immunoglobulin and mucin domain 1 (TIM-1), Axl, Mer, or dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) rendered SH-SY5Y cells susceptible to filovirus glycoprotein-driven transduction. Our study reveals that a lack of attachment factors limits filovirus entry and provides direct experimental support for a model of filoviral cell attachment where host factor usage at the cell surface is highly promiscuous.",2019 Mar 19,"['Zapatero-Belinchón, Francisco J.', 'Dietzel, Erik', 'Dolnik, Olga', 'Döhner, Katinka', 'Costa, Rui', 'Hertel, Barbara', 'Veselkova, Barbora', 'Kirui, Jared', 'Klintworth, Anneke', 'Manns, Michael P.', 'Pöhlmann, Stefan', 'Pietschmann, Thomas', 'Krey, Thomas', 'Ciesek, Sandra', 'Gerold, Gisa', 'Sodeik, Beate', 'Becker, Stephan', 'von Hahn, Thomas']",Viruses,,,False
1fa8ee295da509bade53e2988275c9a5ad214d3f,PMC,T-Cell Response to Viral Hemorrhagic Fevers,http://dx.doi.org/10.3390/vaccines7010011,PMC6466054,30678246,CC BY,"Viral hemorrhagic fevers (VHF) are a group of clinically similar diseases that can be caused by enveloped RNA viruses primarily from the families Arenaviridae, Filoviridae, Hantaviridae, and Flaviviridae. Clinically, this group of diseases has in common fever, fatigue, dizziness, muscle aches, and other associated symptoms that can progress to vascular leakage, bleeding and multi-organ failure. Most of these viruses are zoonotic causing asymptomatic infections in the primary host, but in human beings, the infection can be lethal. Clinical and experimental evidence suggest that the T-cell response is needed for protection against VHF, but can also cause damage to the host, and play an important role in disease pathogenesis. Here, we present a review of the T-cell immune responses to VHF and insights into the possible ways to improve counter-measures for these viral agents.",2019 Jan 22,"['Perdomo-Celis, Federico', 'Salvato, Maria S.', 'Medina-Moreno, Sandra', 'Zapata, Juan C.']",Vaccines (Basel),,,True
f06986bac5a2e4aaba548056be566362badcde9e,PMC,A Single V672F Substitution in the Spike Protein of Field-Isolated PEDV Promotes Cell–Cell Fusion and Replication in VeroE6 Cells,http://dx.doi.org/10.3390/v11030282,PMC6466060,30897856,CC BY,"While porcine epidemic diarrhea virus (PEDV) infects and replicates in enterocytes lining villi of neonatal piglets with high efficiency, naturally isolated variants typically grow poorly in established cell lines, unless adapted by multiple passages. Cells infected with most cell-adapted PEDVs usually displayed large syncytia, a process triggered by the spike protein (S). To identify amino acids responsible for S-mediated syncytium formation, we constructed and characterized chimeric S proteins of the cell-adapted variant, YN144, in which the receptor binding domain (RBD) and S1/S2 cleavage site were replaced with those of a poorly culturable field isolate (G2). We demonstrated that the RBD, not the S1/S2 cleavage site, is critical for syncytium formation mediated by chimeric S proteins. Further mutational analyses revealed that a single mutation at the amino acid residue position 672 (V672F) could enable the chimeric S with the entire RBD derived from the G2 strain to trigger large syncytia. Moreover, recombinant PEDV viruses bearing S of the G2 strain with the single V672F substitution could induce extensive syncytium formation and replicate efficiently in VeroE6 cells stably expressing porcine aminopeptidase N (VeroE6-APN). Interestingly, we also demonstrated that while the V672F mutation is critical for the syncytium formation in VeroE6-APN cells, it exerts a minimal effect in Huh-7 cells, thereby suggesting the difference in receptor preference of PEDV among host cells.",2019 Mar 20,"['Wanitchang, Asawin', 'Saenboonrueng, Janya', 'Kaewborisuth, Challika', 'Srisutthisamphan, Kanjana', 'Jongkaewwattana, Anan']",Viruses,,,True
ca5a2024931abd516addf3c4007d9a5b64432275,PMC,Host Determinants of MERS-CoV Transmission and Pathogenesis,http://dx.doi.org/10.3390/v11030280,PMC6466079,30893947,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that causes respiratory infection in humans, ranging from asymptomatic to severe pneumonia. In dromedary camels, the virus only causes a mild infection but it spreads efficiently between animals. Differences in the behavior of the virus observed between individuals, as well as between humans and dromedary camels, highlight the role of host factors in MERS-CoV pathogenesis and transmission. One of these host factors, the MERS-CoV receptor dipeptidyl peptidase-4 (DPP4), may be a critical determinant because it is variably expressed in MERS-CoV-susceptible species as well as in humans. This could partially explain inter- and intraspecies differences in the tropism, pathogenesis, and transmissibility of MERS-CoV. In this review, we explore the role of DPP4 and other host factors in MERS-CoV transmission and pathogenesis—such as sialic acids, host proteases, and interferons. Further characterization of these host determinants may potentially offer novel insights to develop intervention strategies to tackle ongoing outbreaks.",2019 Mar 19,"['Widagdo, W.', 'Sooksawasdi Na Ayudhya, Syriam', 'Hundie, Gadissa B.', 'Haagmans, Bart L.']",Viruses,,,True
6ab55fd404dc1987435bb3fd1b1a7d02c0951f08,PMC,Neonatal Genetic Delivery of Anti-Respiratory Syncytial Virus (RSV) Antibody by Non-Human Primate-Based Adenoviral Vector to Provide Protection against RSV,http://dx.doi.org/10.3390/vaccines7010003,PMC6466083,30597977,CC BY,"Respiratory syncytial virus (RSV) is one of the leading causes of lower respiratory tract infection in infants. Immunoprophylaxis with the anti-RSV monoclonal antibody, palivizumab, reduces the risk for RSV-related hospitalizations, but its use is restricted to high-risk infants due to the high costs. In this study, we investigated if genetic delivery of anti-RSV antibody to neonatal mice by chimpanzee adenovirus type 7 expressing the murine form of palivizumab (AdC7αRSV) can provide protection against RSV. Intranasal and intramuscular administration of AdC7αRSV to adult mice resulted in similar levels of anti-RSV IgG in the serum. However, only intranasal administration resulted in detectable levels of anti-RSV IgG in the bronchoalveolar lavage fluid. Intranasal administration of AdC7αRSV provided protection against subsequent RSV challenge. Expression of the anti-RSV antibody was prolonged following intranasal administration of AdC7αRSV to neonatal mice. Protection against RSV was confirmed at 6 weeks of age. These data suggest that neonatal genetic delivery of anti-RSV antibody by AdC7αRSV can provide protection against RSV.",2018 Dec 29,"['Gomi, Rika', 'Sharma, Anurag', 'Wu, Wenzhu', 'Worgall, Stefan']",Vaccines (Basel),,,True
76a596754a89e14e0c2d8e7804f1226737d943c0,PMC,Neonatal Genetic Delivery of Anti-Respiratory Syncytial Virus (RSV) Antibody by Non-Human Primate-Based Adenoviral Vector to Provide Protection against RSV,http://dx.doi.org/10.3390/vaccines7010003,PMC6466083,30597977,CC BY,"Respiratory syncytial virus (RSV) is one of the leading causes of lower respiratory tract infection in infants. Immunoprophylaxis with the anti-RSV monoclonal antibody, palivizumab, reduces the risk for RSV-related hospitalizations, but its use is restricted to high-risk infants due to the high costs. In this study, we investigated if genetic delivery of anti-RSV antibody to neonatal mice by chimpanzee adenovirus type 7 expressing the murine form of palivizumab (AdC7αRSV) can provide protection against RSV. Intranasal and intramuscular administration of AdC7αRSV to adult mice resulted in similar levels of anti-RSV IgG in the serum. However, only intranasal administration resulted in detectable levels of anti-RSV IgG in the bronchoalveolar lavage fluid. Intranasal administration of AdC7αRSV provided protection against subsequent RSV challenge. Expression of the anti-RSV antibody was prolonged following intranasal administration of AdC7αRSV to neonatal mice. Protection against RSV was confirmed at 6 weeks of age. These data suggest that neonatal genetic delivery of anti-RSV antibody by AdC7αRSV can provide protection against RSV.",2018 Dec 29,"['Gomi, Rika', 'Sharma, Anurag', 'Wu, Wenzhu', 'Worgall, Stefan']",Vaccines (Basel),,,False
a6d2693a3c3bc48b290f231e8824be62c8f364ff,PMC,Bat Research Networks and Viral Surveillance: Gaps and Opportunities in Western Asia,http://dx.doi.org/10.3390/v11030240,PMC6466127,30857374,CC BY,"Bat research networks and viral surveillance are assumed to be at odds due to seemingly conflicting research priorities. Yet human threats that contribute to declines in bat populations globally also lead to increased transmission and spread of bat-associated viruses, which may pose a threat to global health and food security. In this review, we discuss the importance of and opportunities for multidisciplinary collaborations between bat research networks and infectious disease experts to tackle shared threats that jeopardize bat conservation as well as human and animal health. Moreover, we assess research effort on bats and bat-associated viruses globally, and demonstrate that Western Asia has limited published research and represents a gap for coordinated bat research. The lack of bat research in Western Asia severely limits our capacity to identify and mitigate region-specific threats to bat populations and detect interactions between bats and incidental hosts that promote virus spillover. We detail a regional initiative to establish the first bat research network in Western Asia (i.e., the Western Asia Bat Research Network, WAB-Net), with the aim of integrating ecological research on bats with virus surveillance to find “win-win” solutions that promote bat conservation and safeguard public and animal health across the region.",2019 Mar 10,"['Phelps, Kendra L.', 'Hamel, Luke', 'Alhmoud, Nisreen', 'Ali, Shahzad', 'Bilgin, Rasit', 'Sidamonidze, Ketevan', 'Urushadze, Lela', 'Karesh, William', 'Olival, Kevin J.']",Viruses,,,True
8412853deda865020fb0f86ee6be9acb3ca7408b,PMC,Packaging of Genomic RNA in Positive-Sense Single-Stranded RNA Viruses: A Complex Story,http://dx.doi.org/10.3390/v11030253,PMC6466141,30871184,CC BY,"The packaging of genomic RNA in positive-sense single-stranded RNA viruses is a key part of the viral infectious cycle, yet this step is not fully understood. Unlike double-stranded DNA and RNA viruses, this process is coupled with nucleocapsid assembly. The specificity of RNA packaging depends on multiple factors: (i) one or more packaging signals, (ii) RNA replication, (iii) translation, (iv) viral factories, and (v) the physical properties of the RNA. The relative contribution of each of these factors to packaging specificity is different for every virus. In vitro and in vivo data show that there are different packaging mechanisms that control selective packaging of the genomic RNA during nucleocapsid assembly. The goals of this article are to explain some of the key experiments that support the contribution of these factors to packaging selectivity and to draw a general scenario that could help us move towards a better understanding of this step of the viral infectious cycle.",2019 Mar 13,"Comas-Garcia, Mauricio",Viruses,,,True
d0d330fbfb644da246909905d6537021f7393661,PMC,Bat Coronaviruses in China,http://dx.doi.org/10.3390/v11030210,PMC6466186,30832341,CC BY,"During the past two decades, three zoonotic coronaviruses have been identified as the cause of large-scale disease outbreaks–Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Swine Acute Diarrhea Syndrome (SADS). SARS and MERS emerged in 2003 and 2012, respectively, and caused a worldwide pandemic that claimed thousands of human lives, while SADS struck the swine industry in 2017. They have common characteristics, such as they are all highly pathogenic to humans or livestock, their agents originated from bats, and two of them originated in China. Thus, it is highly likely that future SARS- or MERS-like coronavirus outbreaks will originate from bats, and there is an increased probability that this will occur in China. Therefore, the investigation of bat coronaviruses becomes an urgent issue for the detection of early warning signs, which in turn minimizes the impact of such future outbreaks in China. The purpose of the review is to summarize the current knowledge on viral diversity, reservoir hosts, and the geographical distributions of bat coronaviruses in China, and eventually we aim to predict virus hotspots and their cross-species transmission potential.",2019 Mar 2,"['Fan, Yi', 'Zhao, Kai', 'Shi, Zheng-Li', 'Zhou, Peng']",Viruses,,,True
1c7d1097a0fc23516fc084e127333ec4bbf9ca94,PMC,Ebola Virus Entry: From Molecular Characterization to Drug Discovery,http://dx.doi.org/10.3390/v11030274,PMC6466262,30893774,CC BY,"Ebola Virus Disease (EVD) is one of the most lethal transmissible infections, characterized by a high fatality rate, and caused by a member of the Filoviridae family. The recent large outbreak of EVD in Western Africa (2013–2016) highlighted the worldwide threat represented by the disease and its impact on global public health and the economy. The development of highly needed anti-Ebola virus antivirals has been so far hampered by the shortage of tools to study their life cycle in vitro, allowing to screen for potential active compounds outside a biosafety level-4 (BSL-4) containment. Importantly, the development of surrogate models to study Ebola virus entry in a BSL-2 setting, such as viral pseudotypes and Ebola virus-like particles, tremendously boosted both our knowledge of the viral life cycle and the identification of promising antiviral compounds interfering with viral entry. In this context, the combination of such surrogate systems with large-scale small molecule compounds and haploid genetic screenings, as well as rational drug design and drug repurposing approaches will prove priceless in our quest for the development of a treatment for EVD.",2019 Mar 19,"['Salata, Cristiano', 'Calistri, Arianna', 'Alvisi, Gualtiero', 'Celestino, Michele', 'Parolin, Cristina', 'Palù, Giorgio']",Viruses,,,True
0defab5b2520008da1413d0f75d29fe0ae656ea9,PMC,Can Bats Serve as Reservoirs for Arboviruses?,http://dx.doi.org/10.3390/v11030215,PMC6466281,30832426,CC BY,"Bats are known to harbor and transmit many emerging and re-emerging viruses, many of which are extremely pathogenic in humans but do not cause overt pathology in their bat reservoir hosts: henipaviruses (Nipah and Hendra), filoviruses (Ebola and Marburg), and coronaviruses (SARS-CoV and MERS-CoV). Direct transmission cycles are often implicated in these outbreaks, with virus shed in bat feces, urine, and saliva. An additional mode of virus transmission between bats and humans requiring further exploration is the spread of disease via arthropod vectors. Despite the shared ecological niches that bats fill with many hematophagous arthropods (e.g., mosquitoes, ticks, biting midges, etc.) known to play a role in the transmission of medically important arboviruses, knowledge surrounding the potential for bats to act as reservoirs for arboviruses is limited. To this end, a comprehensive literature review was undertaken examining the current understanding and potential for bats to act as reservoirs for viruses transmitted by blood-feeding arthropods. Serosurveillance and viral isolation from either free-ranging or captive bats are described in relation to four arboviral groups (Bunyavirales, Flaviviridae, Reoviridae, Togaviridae). Further, ecological associations between bats and hematophagous viral vectors are characterized (e.g., bat bloodmeals in mosquitoes, ingestion of mosquitoes by bats, etc). Lastly, knowledge gaps related to hematophagous ectoparasites (bat bugs and bed bugs (Cimicidae) and bat flies (Nycteribiidae and Streblidae)), in addition to future directions for characterization of bat-vector-virus relationships are described.",2019 Mar 3,"['Fagre, Anna C.', 'Kading, Rebekah C.']",Viruses,,,True
0c842a151c9e010a7c70151d029c91a118bde887,PMC,Cellular Innate Immunity against PRRSV and Swine Influenza Viruses,http://dx.doi.org/10.3390/vetsci6010026,PMC6466325,30862035,CC BY,"Porcine respiratory disease complex (PRDC) is a polymicrobial syndrome that results from a combination of infectious agents, such as environmental stressors, population size, management strategies, age, and genetics. PRDC results in reduced performance as well as increased mortality rates and production costs in the pig industry worldwide. This review focuses on the interactions of two enveloped RNA viruses—porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SwIV)—as major etiological agents that contribute to PRDC within the porcine cellular innate immunity during infection. The innate immune system of the porcine lung includes alveolar and parenchymal/interstitial macrophages, neutrophils (PMN), conventional dendritic cells (DC) and plasmacytoid DC, natural killer cells, and γδ T cells, thus the in vitro and in vivo interactions between those cells and PRRSV and SwIV are reviewed. Likewise, the few studies regarding PRRSV-SwIV co-infection are illustrated together with the different modulation mechanisms that are induced by the two viruses. Alterations in responses by natural killer (NK), PMN, or γδ T cells have not received much attention within the scientific community as their counterpart antigen-presenting cells and there are numerous gaps in the knowledge regarding the role of those cells in both infections. This review will help in paving the way for future directions in PRRSV and SwIV research and enhancing the understanding of the innate mechanisms that are involved during infection with these viruses.",2019 Mar 11,"['Crisci, Elisa', 'Fraile, Lorenzo', 'Montoya, Maria']",Vet Sci,,,True
1e8198cb2eac9d910c4f14712025d90ddb958204,PMC,Efficacy of an Adjuvanted Middle East Respiratory Syndrome Coronavirus Spike Protein Vaccine in Dromedary Camels and Alpacas,http://dx.doi.org/10.3390/v11030212,PMC6466352,30832356,CC BY,"MERS-CoV is present in dromedary camels throughout the Middle East and Africa. Dromedary camels are the primary zoonotic reservoir for human infections. Interruption of the zoonotic transmission chain from camels to humans, therefore, may be an effective strategy to control the ongoing MERS-CoV outbreak. Here we show that vaccination with an adjuvanted MERS-CoV Spike protein subunit vaccine confers complete protection from MERS-CoV disease in alpaca and results in reduced and delayed viral shedding in the upper airways of dromedary camels. Protection in alpaca correlates with high serum neutralizing antibody titers. Lower titers of serum neutralizing antibodies correlate with delayed and significantly reduced shedding in the nasal turbinates of dromedary camels. Together, these data indicate that induction of robust neutralizing humoral immune responses by vaccination of naïve animals reduces shedding that potentially could diminish the risk of zoonotic transmission.",2019 Mar 2,"['Adney, Danielle R.', 'Wang, Lingshu', 'van Doremalen, Neeltje', 'Shi, Wei', 'Zhang, Yi', 'Kong, Wing-Pui', 'Miller, Megan R.', 'Bushmaker, Trenton', 'Scott, Dana', 'de Wit, Emmie', 'Modjarrad, Kayvon', 'Petrovsky, Nikolai', 'Graham, Barney S.', 'Bowen, Richard A.', 'Munster, Vincent J.']",Viruses,,,True
4fe69c2885c5d9f51624b581cf56342fad615453,PMC,Efficacy of an Adjuvanted Middle East Respiratory Syndrome Coronavirus Spike Protein Vaccine in Dromedary Camels and Alpacas,http://dx.doi.org/10.3390/v11030212,PMC6466352,30832356,CC BY,"MERS-CoV is present in dromedary camels throughout the Middle East and Africa. Dromedary camels are the primary zoonotic reservoir for human infections. Interruption of the zoonotic transmission chain from camels to humans, therefore, may be an effective strategy to control the ongoing MERS-CoV outbreak. Here we show that vaccination with an adjuvanted MERS-CoV Spike protein subunit vaccine confers complete protection from MERS-CoV disease in alpaca and results in reduced and delayed viral shedding in the upper airways of dromedary camels. Protection in alpaca correlates with high serum neutralizing antibody titers. Lower titers of serum neutralizing antibodies correlate with delayed and significantly reduced shedding in the nasal turbinates of dromedary camels. Together, these data indicate that induction of robust neutralizing humoral immune responses by vaccination of naïve animals reduces shedding that potentially could diminish the risk of zoonotic transmission.",2019 Mar 2,"['Adney, Danielle R.', 'Wang, Lingshu', 'van Doremalen, Neeltje', 'Shi, Wei', 'Zhang, Yi', 'Kong, Wing-Pui', 'Miller, Megan R.', 'Bushmaker, Trenton', 'Scott, Dana', 'de Wit, Emmie', 'Modjarrad, Kayvon', 'Petrovsky, Nikolai', 'Graham, Barney S.', 'Bowen, Richard A.', 'Munster, Vincent J.']",Viruses,,,False
9be40fd878c72fc18e2557ccc3cc8b4ef95a926d,PMC,"Function, Architecture, and Biogenesis of Reovirus Replication Neoorganelles",http://dx.doi.org/10.3390/v11030288,PMC6466366,30901959,CC BY,"Most viruses that replicate in the cytoplasm of host cells form neoorganelles that serve as sites of viral genome replication and particle assembly. These highly specialized structures concentrate viral proteins and nucleic acids, prevent the activation of cell-intrinsic defenses, and coordinate the release of progeny particles. Reoviruses are common pathogens of mammals that have been linked to celiac disease and show promise for oncolytic applications. These viruses form nonenveloped, double-shelled virions that contain ten segments of double-stranded RNA. Replication organelles in reovirus-infected cells are nucleated by viral nonstructural proteins µNS and σNS. Both proteins partition the endoplasmic reticulum to form the matrix of these structures. The resultant membranous webs likely serve to anchor viral RNA–protein complexes for the replication of the reovirus genome and the assembly of progeny virions. Ongoing studies of reovirus replication organelles will advance our knowledge about the strategies used by viruses to commandeer host biosynthetic pathways and may expose new targets for therapeutic intervention against diverse families of pathogenic viruses.",2019 Mar 21,"['Tenorio, Raquel', 'Fernández de Castro, Isabel', 'Knowlton, Jonathan J.', 'Zamora, Paula F.', 'Sutherland, Danica M.', 'Risco, Cristina', 'Dermody, Terence S.']",Viruses,,,True
9464670c290cbe53aef50f1aca3011de96a1333c,PMC,Diversity and Evolution of Viral Pathogen Community in Cave Nectar Bats (Eonycteris spelaea),http://dx.doi.org/10.3390/v11030250,PMC6466414,30871070,CC BY,"Bats are unique mammals, exhibit distinctive life history traits and have unique immunological approaches to suppression of viral diseases upon infection. High-throughput next-generation sequencing has been used in characterizing the virome of different bat species. The cave nectar bat, Eonycteris spelaea, has a broad geographical range across Southeast Asia, India and southern China, however, little is known about their involvement in virus transmission. Here we investigate the diversity and abundance of viral communities from a colony of Eonycteris spelaea residing in Singapore. Our results detected 47 and 22 different virus families from bat fecal and urine samples, respectively. Among these, we identify a large number of virus families including Adenoviridae, Flaviviridae, Reoviridae, Papillomaviridae, Paramyxoviridae, Parvoviridae, Picornaviridae, and Polyomaviridae. In most cases, viral sequences from Eonycteris spelaea are genetically related to a group of bat viruses from other bat genera (e.g., Eidolon, Miniopterus, Rhinolophus and Rousettus). The results of this study improve our knowledge of the host range, spread and evolution of several important viral pathogens. More significantly, our findings provide a baseline to study the temporal patterns of virus shedding and how they correlate with bat phenological trends.",2019 Mar 12,"['Mendenhall, Ian H', 'Wen, Dolyce Low Hong', 'Jayakumar, Jayanthi', 'Gunalan, Vithiagaran', 'Wang, Linfa', 'Mauer-Stroh, Sebastian', 'Su, Yvonne C.F.', 'Smith, Gavin J.D.']",Viruses,,,True
2af1bd7a71e67484330a168ec2aa07e383cef140,PMC,Autophagy Promotes Infectious Particle Production of Mopeia and Lassa Viruses,http://dx.doi.org/10.3390/v11030293,PMC6466445,30909570,CC BY,"Lassa virus (LASV) and Mopeia virus (MOPV) are two closely related Old-World mammarenaviruses. LASV causes severe hemorrhagic fever with high mortality in humans, whereas no case of MOPV infection has been reported. Comparing MOPV and LASV is a powerful strategy to unravel pathogenic mechanisms that occur during the course of pathogenic arenavirus infection. We used a yeast two-hybrid approach to identify cell partners of MOPV and LASV Z matrix protein in which two autophagy adaptors were identified, NDP52 and TAX1BP1. Autophagy has emerged as an important cellular defense mechanism against viral infections but its role during arenavirus infection has not been shown. Here, we demonstrate that autophagy is transiently induced by MOPV, but not LASV, in infected cells two days after infection. Impairment of the early steps of autophagy significantly decreased the production of MOPV and LASV infectious particles, whereas a blockade of the degradative steps impaired only MOPV infectious particle production. Our study provides insights into the role played by autophagy during MOPV and LASV infection and suggests that this process could partially explain their different pathogenicity.",2019 Mar 23,"['Baillet, Nicolas', 'Krieger, Sophie', 'Journeaux, Alexandra', 'Caro, Valérie', 'Tangy, Frédéric', 'Vidalain, Pierre-Olivier', 'Baize, Sylvain']",Viruses,,,True
12834756cf70a24e0bc14906b131ca587f86dc02,PMC,Visual detection of porcine epidemic diarrhea virus using a novel reverse transcription polymerase spiral reaction method,http://dx.doi.org/10.1186/s12917-019-1851-7,PMC6466714,30987635,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is a major etiological agent of porcine epidemic diarrhea around the world. Point-of-care testing in the field is lacking owing to the requirement for a simple, robust field applicable test that does not require professional laboratory equipment. The aim of this study was to establish a novel reverse transcription polymerase spiral reaction (RT-PSR) assay for the rapid detection of porcine epidemic diarrhea virus (PEDV). For the assay, a specific RT-PSR primer pair was designed against a conserved region in PEDV ORF3. RESULTS: The RT-PSR was optimized, and PEDV could be detected after a 50 min incubation at 62 °C, in addition to the 15 min required for reverse transcription. No cross-reaction with other porcine infectious viruses was observed. This new method for PEDV detection was 10 times more sensitive than the conventional reverse transcription-polymerase chain reaction (RT-PCR) assay. The positive rates for 65 clinical samples using the new RT-PSR assay and the conventional RT-PCR assay were 58.46% (38/65) and 53.84% (35/65), respectively. In the RT-PSR assay, the addition of a mixture of dyes allowed a positive reaction to be directly observed by the naked eye. CONCLUSIONS: These results indicate that this RT-PSR assay is capable of accurately detecting PEDV, and has the advantages of high specificity and sensitivity for the detection of PEDV.",2019 Apr 15,"['Wang, Xueyu', 'Xu, Xin', 'Hu, Wen', 'Zuo, Kejing', 'Li, Zhili', 'Kan, Yunchao', 'Yao, Lunguang', 'Ji, Jun', 'Bi, Yingzuo']",BMC Vet Res,,,True
8ef6b31ac51e4560b97074574711f05a2a30c845,PMC,Pentraxin 3 Detects Clinically Significant Fibrosis in Patients with Chronic Viral Hepatitis C,http://dx.doi.org/10.1155/2019/2639248,PMC6466943,31061822,CC BY,"Pentraxin 3 (PTX3) plays a pathogenic role in experimental models of chronic liver injury and contributes to the progression of fibrosis. The detection of advanced fibrosis (METAVIR F≥3) is important to identify patients who are in urgent need of antiviral treatments versus those whose treatment could be deferred (F≥2). The aim was to assess the diagnostic value of PTX3 as a potential biomarker for clinically significant and advanced fibrosis. PTX3 associations with biochemical and histological parameters of inflammatory activity and fibrosis were investigated in 138 patients with chronic viral hepatitis C (HCV) before antiviral treatment. METAVIR histological scores of activity and fibrosis were obtained. PTX3 was measured by enzyme-linked immunosorbent assay. The diagnostic accuracy of serum PTX3 levels was compared to that of other fibrosis markers, including transforming growth factor‐β(1) (TGF-β(1)), hyaluronic acid (HA), aspartate transaminase to platelet ratio index (APRI), fibrosis score based on four factors (FIB4), gamma-glutamyltranspeptidase to platelet ratio (GPR), and the liver stiffness measurement (LSM) by transient elastography (FibroScan®). In HCV patients the PTX3 level increased in parallel with the METAVIR histological score of activity, being independently associated with the METAVIR fibrosis score (P < 0.001). Using the receiver operating characteristics analysis, the best marker for detecting F≥2 and F≥3 was PTX3 with AUC = 0.802 and AUC = 0.867, respectively. The area under the curve of PTX3 for predicting significant fibrosis (F≥2) was significantly greater than those for the GPR ratio (AUC = 0.648) and FIB-4 score (AUC = 0.770) and similar to that for APRI index (AUC = 0.831). PTX3 provided clinically relevant diagnostic accuracy as a single marker of significant fibrosis.",2019 Apr 2,"['Gorka-Dynysiewicz, Joanna', 'Pazgan-Simon, Monika', 'Zuwala-Jagiello, Jolanta']",Biomed Res Int,,,True
485b039c35ff2b0b0d592af3856fd9de63d47d01,PMC,Longitudinal active sampling for respiratory viral infections across age groups,http://dx.doi.org/10.1111/irv.12629,PMC6468062,30770641,CC BY,"BACKGROUND: Respiratory viral infections are a major cause of morbidity and mortality worldwide. However, their characterization is incomplete because prevalence estimates are based on syndromic surveillance data. Here, we address this shortcoming through the analysis of infection rates among individuals tested regularly for respiratory viral infections, irrespective of their symptoms. METHODS: We carried out longitudinal sampling and analysis among 214 individuals enrolled at multiple New York City locations from fall 2016 to spring 2018. We combined personal information with weekly nasal swab collection to investigate the prevalence of 18 respiratory viruses among different age groups and to assess risk factors associated with infection susceptibility. RESULTS: 17.5% of samples were positive for respiratory viruses. Some viruses circulated predominantly during winter, whereas others were found year round. Rhinovirus and coronavirus were most frequently detected. Children registered the highest positivity rates, and adults with daily contacts with children experienced significantly more infections than their counterparts without children. CONCLUSION: Respiratory viral infections are widespread among the general population with the majority of individuals presenting multiple infections per year. The observations identify children as the principal source of respiratory infections. These findings motivate further active surveillance and analysis of differences in pathogenicity among respiratory viruses.",2019 May 15,"['Galanti, Marta', 'Birger, Ruthie', 'Ud‐Dean, Minhaz', 'Filip, Ioan', 'Morita, Haruka', 'Comito, Devon', 'Anthony, Simon', 'Freyer, Greg A.', 'Ibrahim, Sadiat', 'Lane, Benjamin', 'Ligon, Chanel', 'Rabadan, Raul', 'Shittu, Atinuke', 'Tagne, Eudosie', 'Shaman, Jeffrey']",Influenza Other Respir Viruses,,,True
e5c0ca285de27831edf5b0306750cfa3f69eba8e,PMC,"Influenza surveillance in Middle East, North, East and South Africa: Report of the 8th MENA Influenza Stakeholders Network",http://dx.doi.org/10.1111/irv.12628,PMC6468068,30801995,CC BY,"The Middle‐East and Africa Influenza Surveillance Network (MENA‐ISN), established in 2014, includes 15 countries at present. Country representatives presented their influenza surveillance programmes, vaccine coverage and influenza control actions achieved, and provided a list of country surveillance/control objectives for the upcoming 3 years. This report details the current situation of influenza surveillance and action plans to move forward in MENA‐ISN countries. Data were presented at the 8th MENA‐ISN meeting, organized by the Mérieux Foundation that was held on 10‐11 April 2018 in Cairo, Egypt. The meeting included MENA‐ISN representatives from 12 countries (Algeria, Egypt, Jordan, Kenya, Lebanon, Libya, Morocco, Pakistan, Saudi Arabia, South Africa, Tunisia and United Arab Emirates) and experts from the Canadian Centre for Vaccinology, and the World Health Organization. Meeting participants concluded that influenza remains a significant threat especially in high‐risk groups (children under‐5, elderly, pregnant women and immunosuppressed individuals) in the MENA‐ISN region. Additional funding and planning are required by member countries to contain this threat. Future meetings will need to focus on creative and innovative ways to inform policy and initiatives for vaccination, surveillance and management of influenza‐related morbidity and mortality especially among the most vulnerable groups of the population.",2019 May 22,"['Abusrewil, Suleiman', 'Algeer, Abdulrahman', 'Aljifri, Alanoud', 'Al Slail, Fatima', 'Andrew, Melissa K.', 'Awad Tag Eldin, Mohamed', 'Al Awaidy, Salah', 'Ben Alaya, Nissaf', 'Ben Khelil, Jalila', 'Dbaibo, Ghassan', 'Derrar, Fawzi', 'Elahmer, Omar', 'Ghosn, Nada', 'Gabriel, Guelsah', 'Grasso, Cindy', 'Hassan, Mohamed', 'Hirve, Siddhivinayak', 'Mirza, Yusuf Kamal', ""Rateb, Yousef Moh'd"", 'Nourlil, Jalal', 'Nunes, Marta C.', 'Omaima, Idris', 'Malande, Oliver Ombeva', 'Saadatian‐Elahi, Mitra', 'Sanchez‐Picot, Valentina', 'Sk. Mamunur Rahman, Malik', 'Tarraf, Hesham', 'Walaza, Sibongile']",Influenza Other Respir Viruses,,,True
afd61adb91428007558db20c6234a77695c8851c,PMC,Influenza B associated paediatric acute respiratory infection hospitalization in central vietnam,http://dx.doi.org/10.1111/irv.12626,PMC6468073,30575288,CC BY,"BACKGROUND: Influenza B is one of the major etiologies for acute respiratory infections (ARI) among children worldwide; however, its clinical‐epidemiological information is limited. We aimed to investigate the hospitalization incidence and clinical‐epidemiological characteristics of influenza B‐associated paediatric ARIs in central Vietnam. METHODS: We collected clinical‐epidemiological information and nasopharyngeal swabs from ARI children hospitalized at Khanh Hoa General Hospital, Nha Trang, Vietnam from February 2007 through June 2013. Nasopharyngeal samples were screened for 13 respiratory viruses using Multiplex‐PCRs. Influenza B‐confirmed cases were genotyped by Haemagglutinin gene sequencing. We analyzed the clinical‐epidemiological characteristics of influenza B Lineages (Victoria/Yamagata) and WHO Groups. RESULTS: In the pre‐A/H1N1pdm09 period, influenza B‐associated ARI hospitalization incidence among children under five was low, ranging between 14.7 and 80.7 per 100 000 population. The incidence increased to between 51.4 and 330 in the post‐A/H1N1pdm09. Influenza B ARI cases were slightly older with milder symptoms. Both Victoria and Yamagata lineages were detected before the A/H1N1pdm09 outbreak; however, Victoria lineage became predominant in 2010‐2013 (84% Victoria vs 16% Yamagata). Victoria and Yamagata lineages did not differ in demographic and clinical characteristics. In Victoria lineage, Group1 ARI cases were clinically more severe compared to Group5, presenting a greater proportion of wheeze, tachypnea, and lower respiratory tract infection. CONCLUSIONS: The current results highlight the increased incidence of influenza B‐related ARI hospitalization among children in central Vietnam in the post‐A/H1N1pdm09 era. Furthermore, the difference in clinical severity between Victoria lineage Group1 and 5 implies the importance of influenza B genetic variation on clinical presentation.",2019 May 28,"['Yoshihara, Keisuke', 'Le, Minh Nhat', 'Toizumi, Michiko', 'Nguyen, Hien Anh', 'Vo, Hien Minh', 'Odagiri, Takato', 'Fujisaki, Seiichiro', 'Ariyoshi, Koya', 'Moriuchi, Hiroyuki', 'Hashizume, Masahiro', 'Dang, Duc Anh', 'Yoshida, Lay‐Myint']",Influenza Other Respir Viruses,,,True
256b5eac8bfa8c9641d0d210032e64b82294b597,PMC,Functional Interplay between RNA Viruses and Non-Coding RNA in Mammals,http://dx.doi.org/10.3390/ncrna5010007,PMC6468702,30646609,CC BY,"Exploring virus–host interactions is key to understand mechanisms regulating the viral replicative cycle and any pathological outcomes associated with infection. Whereas interactions at the protein level are well explored, RNA interactions are less so. Novel sequencing methodologies have helped uncover the importance of RNA–protein and RNA–RNA interactions during infection. In addition to messenger RNAs (mRNAs), mammalian cells express a great number of regulatory non-coding RNAs, some of which are crucial for regulation of the immune system whereas others are utilized by viruses. It is thus becoming increasingly clear that RNA interactions play important roles for both sides in the arms race between virus and host. With the emerging field of RNA therapeutics, such interactions are promising antiviral targets. In this review, we discuss direct and indirect RNA interactions occurring between RNA viruses or retroviruses and host non-coding transcripts upon infection. In addition, we review RNA virus derived non-coding RNAs affecting immunological and metabolic pathways of the host cell typically to provide an advantage to the virus. The relatively few known examples of virus–host RNA interactions suggest that many more await discovery.",2019 Jan 14,"['Damas, Nkerorema Djodji', 'Fossat, Nicolas', 'Scheel, Troels K. H.']",Noncoding RNA,,,True
e47d1f361bc4007b3fd859fd80fda5b40cc4a684,PMC,Expression profile analysis of 5-day-old neonatal piglets infected with porcine Deltacoronavirus,http://dx.doi.org/10.1186/s12917-019-1848-2,PMC6469071,30992015,CC BY,"BACKGROUND: Porcine deltacoronavirus (PDCoV) is a novel coronavirus that can cause diarrhea in nursing piglets. This study was aimed to investigate the roles of host differentially expressed genes on metabolic pathways in PDCoV infections. RESULTS: Twenty thousand six hundred seventy-four differentially expressed mRNAs were identified in 5-day-old piglets responded to PDCoV experimental infections. Many of these genes were correlated to the basic metabolism, such as the peroxisome proliferator-activated receptor (PPAR) signaling pathway which plays a critical role in digestion. At the same time, in the PPAR pathway genes of fatty acid-binding protein (FABP) family members were observed with remarkably differential expressions. The differential expressed genes were associated with appetite decrease and weight loss of PDCoV- affected piglets. DISCUSSION: Fatty acid-binding protein 1 (FABP1) and fatty acid-binding protein 3 (FABP3) were found to be regulated by PDCoV. These two genes not only mediate fatty acid transportation to different cell organelles such as mitochondria, peroxisome, endoplasmic reticulum and nucleus, but also modulate fatty acid metabolism and storage as a signaling molecule outside the cell. Therefore, it can be preliminarily concluded that PPAR differential expression caused by PDCoV was mostly associated with weight loss and death from emaciation. CONCLUSIONS: The host differentially expressed genes were associated with infection response, metabolism signaling and organismal systems signaling pathways. The genes of FABP family members in the PPAR signaling pathway were the most highly altered and played important roles in metabolism. Alteration of these genes were most likely the reason of weight loss and other clinical symptoms. Our results provided new insights into the metabolic mechanisms and pathogenesis of PDCoV infection. METHODS: Animal experiment, Determination of viral growth by real-time RT-PCR, Histopathology, Immunohistochemical staining, Microarray analysis.",2019 Apr 16,"['Wu, Jiao L.', 'Mai, Kai J.', 'Li, Di', 'Wu, Rui T.', 'Wu, Zi X.', 'Tang, Xiao Y.', 'Li, Qian N.', 'Sun, Yuan', 'Lan, Tian', 'Zhang, Xiang B.', 'Ma, Jing Y.']",BMC Vet Res,,,True
5b9d05c782f514a4e87b8dd1639ee2fc7a6b1ab0,PMC,Effect of stochasticity on coinfection dynamics of respiratory viruses,http://dx.doi.org/10.1186/s12859-019-2793-6,PMC6469119,30991939,CC BY,"BACKGROUND: Respiratory viral infections are a leading cause of mortality worldwide. As many as 40% of patients hospitalized with influenza-like illness are reported to be infected with more than one type of virus. However, it is not clear whether these infections are more severe than single viral infections. Mathematical models can be used to help us understand the dynamics of respiratory viral coinfections and their impact on the severity of the illness. Most models of viral infections use ordinary differential equations (ODE) that reproduce the average behavior of the infection, however, they might be inaccurate in predicting certain events because of the stochastic nature of viral replication cycle. Stochastic simulations of single virus infections have shown that there is an extinction probability that depends on the size of the initial viral inoculum and parameters that describe virus-cell interactions. Thus the coinfection dynamics predicted by the ODE might be difficult to observe in reality. RESULTS: In this work, a continuous-time Markov chain (CTMC) model is formulated to investigate probabilistic outcomes of coinfections. This CTMC model is based on our previous coinfection model, expressed in terms of a system of ordinary differential equations. Using the Gillespie method for stochastic simulation, we examine whether stochastic effects early in the infection can alter which virus dominates the infection. CONCLUSIONS: We derive extinction probabilities for each virus individually as well as for the infection as a whole. We find that unlike the prediction of the ODE model, for similar initial growth rates stochasticity allows for a slower growing virus to out-compete a faster growing virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-019-2793-6) contains supplementary material, which is available to authorized users.",2019 Apr 16,"['Pinky, Lubna', 'Gonzalez-Parra, Gilberto', 'Dobrovolny, Hana M.']",BMC Bioinformatics,,,False
6fea71c8f426d1dd72886aeca6e4f7c1c98f21fa,PMC,Effect of stochasticity on coinfection dynamics of respiratory viruses,http://dx.doi.org/10.1186/s12859-019-2793-6,PMC6469119,30991939,CC BY,"BACKGROUND: Respiratory viral infections are a leading cause of mortality worldwide. As many as 40% of patients hospitalized with influenza-like illness are reported to be infected with more than one type of virus. However, it is not clear whether these infections are more severe than single viral infections. Mathematical models can be used to help us understand the dynamics of respiratory viral coinfections and their impact on the severity of the illness. Most models of viral infections use ordinary differential equations (ODE) that reproduce the average behavior of the infection, however, they might be inaccurate in predicting certain events because of the stochastic nature of viral replication cycle. Stochastic simulations of single virus infections have shown that there is an extinction probability that depends on the size of the initial viral inoculum and parameters that describe virus-cell interactions. Thus the coinfection dynamics predicted by the ODE might be difficult to observe in reality. RESULTS: In this work, a continuous-time Markov chain (CTMC) model is formulated to investigate probabilistic outcomes of coinfections. This CTMC model is based on our previous coinfection model, expressed in terms of a system of ordinary differential equations. Using the Gillespie method for stochastic simulation, we examine whether stochastic effects early in the infection can alter which virus dominates the infection. CONCLUSIONS: We derive extinction probabilities for each virus individually as well as for the infection as a whole. We find that unlike the prediction of the ODE model, for similar initial growth rates stochasticity allows for a slower growing virus to out-compete a faster growing virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-019-2793-6) contains supplementary material, which is available to authorized users.",2019 Apr 16,"['Pinky, Lubna', 'Gonzalez-Parra, Gilberto', 'Dobrovolny, Hana M.']",BMC Bioinformatics,,,True
94a14012df753e9d47400bf1b660d7559e4976d2,PMC,Respiratory tract virus infections in the elderly with pneumonia,http://dx.doi.org/10.1186/s12877-019-1125-z,PMC6469155,30991957,CC BY,"BACKGROUND: In children suffering from severe lower airway illnesses, respiratory virus detection has given good prognostic information, but such reports in the elderly are scarce. Therefore, our aim was to study whether the detection of nasopharyngeal viral pathogens and conventional inflammatory markers in the frail elderly correlate to the presence, signs and symptoms or prognosis of radiographically-verified pneumonia. METHODS: Consecutive episodes of hospital care of patients 65 years and older with respiratory symptoms (N = 382) were prospectively studied as a cohort. Standard clinical questionnaire was filled by the study physician. Laboratory analyses included PCR diagnostics of nasopharyngeal swab samples for 14 respiratory viruses, C-reactive protein (CRP) and white blood cell count (WBC). Chest radiographs were systematically analysed by a study radiologist. The length of hospital stay, hospital revisit and death at ward were used as clinical endpoints. RESULTS: Median age of the patients was 83 years (range 76–90). Pneumonia was diagnosed in 112/382 (29%) of the studied episodes. One or more respiratory viruses were detected in 141/382 (37%) episodes and in 34/112 (30%) episodes also diagnosed with pneumonia. Pneumonia was associated with a WBC over 15 × 10(9)/L (P = .006) and a CRP value over 80 mg/l (P < .05). A virus was detected in 30% of pneumonia episodes and in 40% of non-pneumonia episodes, but this difference was not significant (P = 0.09). The presence of a respiratory virus was associated with fewer revisits to the hospital (P < .05), whereas a CRP value over 100 mg/l was associated with death during hospital stay (P < .05). Respiratory virus detections did not correlate to WBC or CRP values, signs and symptoms or prognosis of radiographically-verified pneumonia episodes. CONCLUSION: Among the elderly with respiratory symptoms, respiratory virus detection was not associated with an increased risk of pneumonia or with a more severe clinical course of the illness. CRP and WBC remain important indicators of pneumonia, and according to our findings, pneumonia should be treated as a bacterial disease regardless of the virus findings. Our data does not support routine virus diagnostics for the elderly patients with pneumonia outside the epidemic seasons. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12877-019-1125-z) contains supplementary material, which is available to authorized users.",2019 Apr 16,"['Aronen, Matti', 'Viikari, Laura', 'Kohonen, Ia', 'Vuorinen, Tytti', 'Hämeenaho, Mira', 'Wuorela, Maarit', 'Sadeghi, Mohammadreza', 'Söderlund-Venermo, Maria', 'Viitanen, Matti', 'Jartti, Tuomas']",BMC Geriatr,,,True
55c55a0a490f47268c4690097420923bbb581956,PMC,Virus–Host Interactions Involved in Lassa Virus Entry and Genome Replication,http://dx.doi.org/10.3390/pathogens8010017,PMC6470645,30699976,CC BY,"Lassa virus (LASV) is the causative agent of Lassa fever, a human hemorrhagic disease associated with high mortality and morbidity rates, particularly prevalent in West Africa. Over the past few years, a significant amount of novel information has been provided on cellular factors that are determinant elements playing a role in arenavirus multiplication. In this review, we focus on host proteins that intersect with the initial steps of the LASV replication cycle: virus entry and genome replication. A better understanding of relevant virus–host interactions essential for sustaining these critical steps may help to identify possible targets for the rational design of novel therapeutic approaches against LASV and other arenaviruses that cause severe human disease.",2019 Jan 29,"['Loureiro, María Eugenia', 'D’Antuono, Alejandra', 'López, Nora']",Pathogens,,,True
6b74be7b5e6870fb9f10027347b2ad067aa8b4d5,PMC,Targeted NGS Platforms for Genetic Screening and Gene Discovery in Primary Immunodeficiencies,http://dx.doi.org/10.3389/fimmu.2019.00316,PMC6470723,31031743,CC BY,"Background: Primary Immunodeficiencies (PIDs) are a heterogeneous group of genetic immune disorders. While some PIDs can manifest with more than one phenotype, signs, and symptoms of various PIDs overlap considerably. Recently, novel defects in immune-related genes and additional variants in previously reported genes responsible for PIDs have been successfully identified by Next Generation Sequencing (NGS), allowing the recognition of a broad spectrum of disorders. Objective: To evaluate the strength and weakness of targeted NGS sequencing using custom-made Ion Torrent and Haloplex (Agilent) panels for diagnostics and research purposes. Methods: Five different panels including known and candidate genes were used to screen 105 patients with distinct PID features divided in three main PID categories: T cell defects, Humoral defects and Other PIDs. The Ion Torrent sequencing platform was used in 73 patients. Among these, 18 selected patients without a molecular diagnosis and 32 additional patients were analyzed by Haloplex enrichment technology. Results: The complementary use of the two custom-made targeted sequencing approaches allowed the identification of causative variants in 28.6% (n = 30) of patients. Twenty-two out of 73 (34.6%) patients were diagnosed by Ion Torrent. In this group 20 were included in the SCID/CID category. Eight out of 50 (16%) patients were diagnosed by Haloplex workflow. Ion Torrent method was highly successful for those cases with well-defined phenotypes for immunological and clinical presentation. The Haloplex approach was able to diagnose 4 SCID/CID patients and 4 additional patients with complex and extended phenotypes, embracing all three PID categories in which this approach was more efficient. Both technologies showed good gene coverage. Conclusions: NGS technology represents a powerful approach in the complex field of rare disorders but its different application should be weighted. A relatively small NGS target panel can be successfully applied for a robust diagnostic suspicion, while when the spectrum of clinical phenotypes overlaps more than one PID an in-depth NGS analysis is required, including also whole exome/genome sequencing to identify the causative gene.",2019 Apr 11,"['Cifaldi, Cristina', 'Brigida, Immacolata', 'Barzaghi, Federica', 'Zoccolillo, Matteo', 'Ferradini, Valentina', 'Petricone, Davide', 'Cicalese, Maria Pia', 'Lazarevic, Dejan', 'Cittaro, Davide', 'Omrani, Maryam', 'Attardi, Enrico', 'Conti, Francesca', 'Scarselli, Alessia', 'Chiriaco, Maria', 'Di Cesare, Silvia', 'Licciardi, Francesco', 'Davide, Montin', 'Ferrua, Francesca', 'Canessa, Clementina', 'Pignata, Claudio', 'Giliani, Silvia', 'Ferrari, Simona', 'Fousteri, Georgia', 'Barera, Graziano', 'Merli, Pietro', 'Palma, Paolo', 'Cesaro, Simone', 'Gattorno, Marco', 'Trizzino, Antonio', 'Moschese, Viviana', 'Chini, Loredana', 'Villa, Anna', 'Azzari, Chiara', 'Finocchi, Andrea', 'Locatelli, Franco', 'Rossi, Paolo', 'Sangiuolo, Federica', 'Aiuti, Alessandro', 'Cancrini, Caterina', 'Di Matteo, Gigliola']",Front Immunol,,,True
e7a4eae5bc97a5dc97189e3faa40ef9a91bb3207,PMC,"A Systematic Review of Phytochemistry, Pharmacology and Pharmacokinetics on Astragali Radix: Implications for Astragali Radix as a Personalized Medicine",http://dx.doi.org/10.3390/ijms20061463,PMC6470777,30909474,CC BY,"Astragali radix (AR) is one of the most widely used traditional Chinese herbal medicines. Modern pharmacological studies and clinical practices indicate that AR possesses various biological functions, including potent immunomodulation, antioxidant, anti-inflammation and antitumor activities. To date, more than 200 chemical constituents have been isolated and identified from AR. Among them, isoflavonoids, saponins and polysaccharides are the three main types of beneficial compounds responsible for its pharmacological activities and therapeutic efficacy. After ingestion of AR, the metabolism and biotransformation of the bioactive compounds were extensive in vivo. The isoflavonoids and saponins and their metabolites are the major type of constituents absorbed in plasma. The bioavailability barrier (BB), which is mainly composed of efflux transporters and conjugating enzymes, is expected to have a significant impact on the bioavailability of AR. This review summarizes studies on the phytochemistry, pharmacology and pharmacokinetics on AR. Additionally, the use of AR as a personalized medicine based on the BB is also discussed, which may provide beneficial information to achieve a better and more accurate therapeutic response of AR in clinical practice.",2019 Mar 22,"['Guo, Zhenzhen', 'Lou, Yanmei', 'Kong, Muyan', 'Luo, Qing', 'Liu, Zhongqiu', 'Wu, Jinjun']",Int J Mol Sci,,,True
d3a809d8853624054040f382feb05893b9f6cb7a,PMC,Dereplication by High-Performance Liquid Chromatography (HPLC) with Quadrupole-Time-of-Flight Mass Spectroscopy (qTOF-MS) and Antiviral Activities of Phlorotannins from Ecklonia cava,http://dx.doi.org/10.3390/md17030149,PMC6471242,30836593,CC BY,"Ecklonia cava is edible seaweed that is found in Asian countries, such as Japan and Korea; and, its major components include fucoidan and phlorotannins. Phlorotannins that are isolated from E. cava are well-known to have an antioxidant effect and strong antiviral activity against porcine epidemic diarrhea virus (PEDV), which has a high mortality rate in piglets. In this study, the bioactive components were determined based on two different approaches: (i) bio-guided isolation using the antiviral activity against the H1N1 viral strain, which is a representative influenza virus that originates from swine and (ii) high-resolution mass spectrometry-based dereplication, including relative mass defects (RMDs) and HPLC-qTOFMS fragmentation analysis. The EC70 fraction showed the strongest antiviral activity and contained thirteen phlorotannins, which were predicted by dereplication. Ten compounds were directly isolated from E. cava extract and then identified. Moreover, the dereplication method allowed for the discovery of two new phlorotannins. The structures of these two isolated compounds were elucidated using NMR techniques and HPLC-qTOFMS fragmentation analysis. In addition, molecular modelling was applied to determine the absolute configurations of the two new compounds. The antiviral activities of seven major phlorotannins in active fraction were evaluated against two influenza A viral strains (H1N1 and H9N2). Six of the compounds showed moderate to strong effects on both of the viruses and phlorofucofuroeckol A (12), which showed an EC(50) value of 13.48 ± 1.93 μM, is a potential active antiviral component of E. cava.",2019 Mar 4,"['Cho, Hyo Moon', 'Doan, Thi Phuong', 'Ha, Thi Kim Quy', 'Kim, Hyun Woo', 'Lee, Ba Wool', 'Pham, Ha Thanh Tung', 'Cho, Tae Oh', 'Oh, Won Keun']",Mar Drugs,,,True
88e421b846bdacb07fbf712e5ed5c4394be25fac,PMC,Dereplication by High-Performance Liquid Chromatography (HPLC) with Quadrupole-Time-of-Flight Mass Spectroscopy (qTOF-MS) and Antiviral Activities of Phlorotannins from Ecklonia cava,http://dx.doi.org/10.3390/md17030149,PMC6471242,30836593,CC BY,"Ecklonia cava is edible seaweed that is found in Asian countries, such as Japan and Korea; and, its major components include fucoidan and phlorotannins. Phlorotannins that are isolated from E. cava are well-known to have an antioxidant effect and strong antiviral activity against porcine epidemic diarrhea virus (PEDV), which has a high mortality rate in piglets. In this study, the bioactive components were determined based on two different approaches: (i) bio-guided isolation using the antiviral activity against the H1N1 viral strain, which is a representative influenza virus that originates from swine and (ii) high-resolution mass spectrometry-based dereplication, including relative mass defects (RMDs) and HPLC-qTOFMS fragmentation analysis. The EC70 fraction showed the strongest antiviral activity and contained thirteen phlorotannins, which were predicted by dereplication. Ten compounds were directly isolated from E. cava extract and then identified. Moreover, the dereplication method allowed for the discovery of two new phlorotannins. The structures of these two isolated compounds were elucidated using NMR techniques and HPLC-qTOFMS fragmentation analysis. In addition, molecular modelling was applied to determine the absolute configurations of the two new compounds. The antiviral activities of seven major phlorotannins in active fraction were evaluated against two influenza A viral strains (H1N1 and H9N2). Six of the compounds showed moderate to strong effects on both of the viruses and phlorofucofuroeckol A (12), which showed an EC(50) value of 13.48 ± 1.93 μM, is a potential active antiviral component of E. cava.",2019 Mar 4,"['Cho, Hyo Moon', 'Doan, Thi Phuong', 'Ha, Thi Kim Quy', 'Kim, Hyun Woo', 'Lee, Ba Wool', 'Pham, Ha Thanh Tung', 'Cho, Tae Oh', 'Oh, Won Keun']",Mar Drugs,,,True
9599f421f59c01ea41789ba70c79330cdea8e1d2,PMC,An Overview of the Most Significant Zoonotic Viral Pathogens Transmitted from Animal to Human in Saudi Arabia,http://dx.doi.org/10.3390/pathogens8010025,PMC6471281,30813309,CC BY,"Currently, there has been an increasing socioeconomic impact of zoonotic pathogens transmitted from animals to humans worldwide. Recently, in the Arabian Peninsula, including in Saudi Arabia, epidemiological data indicated an actual increase in the number of emerging and/or reemerging cases of several viral zoonotic diseases. Data presented in this review are very relevant because Saudi Arabia is considered the largest country in the Peninsula. We believe that zoonotic pathogens in Saudi Arabia remain an important public health problem; however, more than 10 million Muslim pilgrims from around 184 Islamic countries arrive yearly at Makkah for the Hajj season and/or for the Umrah. Therefore, for health reasons, several countries recommend vaccinations for various zoonotic diseases among preventive protocols that should be complied with before traveling to Saudi Arabia. However, there is a shortage of epidemiological data focusing on the emerging and reemerging of zoonotic pathogens transmitted from animal to humans in different densely populated cities and/or localities in Saudi Arabia. Therefore, further efforts might be needed to control the increasing impacts of zoonotic viral disease. Also, there is a need for a high collaboration to enhance the detection and determination of the prevalence, diagnosis, control, and prevention as well as intervention and reduction in outbreaks of these diseases in Saudi Arabia, particularly those from other countries. Persons in the health field including physicians and veterinarians, pet owners, pet store owners, exporters, border guards, and people involved in businesses related to animal products have adopted various preventive strategies. Some of these measures might pave the way to highly successful prevention and control results on the different transmission routes of these viral zoonotic diseases from or to Saudi Arabia. Moreover, the prevention of these viral pathogens depends on socioeconomic impacts, available data, improved diagnosis, and highly effective therapeutics or prophylaxis.",2019 Feb 22,"Al-Tayib, Omar A.",Pathogens,,,True
665337fda98a7d10a291ae640001a65017960049,PMC,Tuning Optical and Granulometric Properties of Gold Nanostructures Synthesized with the Aid of Different Types of Honeys for Microwave-Induced Hyperthermia,http://dx.doi.org/10.3390/ma12060898,PMC6471425,30889837,CC BY,"Size-controlled gold nanoparticles (AuNPs) were synthesised with solutions of three types of Polish honeys (lime, multiflower, honeydew) and used in microwave-induced hyperthermia cancer treatment. Optical and structural properties of nanostructures were optimized in reference to measurements made by using UV/Vis absorption spectrophotometry (UV/Vis), transmission electron microscopy (TEM) supported by energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and attenuated total reflectance Fourier transformation infrared spectroscopy (ATR FT-IR). In addition, concentrations of reducing sugars and polyphenols of honeys applied were determined to reveal the role of these chemical compounds in green synthesis of AuNPs. It was found that the smallest AuNPs (20.6 ± 23.3 nm) were produced using a 20% (w/v) multiflower aqueous honey solution and 25 mg·L(−1) of Au(III) ions. These AuNPs were then employed in microwave-induced hyperthermia in a system simulating metastatic tissues. This research illustrated that AuNPs, as produced with the aid of a multiflower honey solution, could be suitably used for microwave-induced heating of cancer. A fluid containing resultant Au nanostructures, as compared to water, revealed facilitated heating and the ability to maintain a temperature of 45 °C required for hyperthermia treatment.",2019 Mar 18,"['Dzimitrowicz, Anna', 'Cyganowski, Piotr', 'Jamroz, Piotr', 'Jermakowicz-Bartkowiak, Dorota', 'Rzegocka, Malgorzata', 'Cwiklinska, Agnieszka', 'Pohl, Pawel']",Materials (Basel),,,True
6a45821b7c9010079cc6021326c1fc2f5cb05e13,PMC,"Progression of Cystic Fibrosis Lung Disease from Childhood to Adulthood: Neutrophils, Neutrophil Extracellular Trap (NET) Formation, and NET Degradation",http://dx.doi.org/10.3390/genes10030183,PMC6471578,30813645,CC BY,"Genetic defects in cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene cause CF. Infants with CFTR mutations show a peribronchial neutrophil infiltration prior to the establishment of infection in their lung. The inflammatory response progressively increases in children that include both upper and lower airways. Infectious and inflammatory response leads to an increase in mucus viscosity and mucus plugging of small and medium-size bronchioles. Eventually, neutrophils chronically infiltrate the airways with biofilm or chronic bacterial infection. Perpetual infection and airway inflammation destroy the lungs, which leads to increased morbidity and eventual mortality in most of the patients with CF. Studies have now established that neutrophil cytotoxins, extracellular DNA, and neutrophil extracellular traps (NETs) are associated with increased mucus clogging and lung injury in CF. In addition to opportunistic pathogens, various aspects of the CF airway milieux (e.g., airway pH, salt concentration, and neutrophil phenotypes) influence the NETotic capacity of neutrophils. CF airway milieu may promote the survival of neutrophils and eventual pro-inflammatory aberrant NETosis, rather than the anti-inflammatory apoptotic death in these cells. Degrading NETs helps to manage CF airway disease; since DNAse treatment release cytotoxins from the NETs, further improvements are needed to degrade NETs with maximal positive effects. Neutrophil-T cell interactions may be important in regulating viral infection-mediated pulmonary exacerbations in patients with bacterial infections. Therefore, clarifying the role of neutrophils and NETs in CF lung disease and identifying therapies that preserve the positive effects of neutrophils, while reducing the detrimental effects of NETs and cytotoxic components, are essential in achieving innovative therapeutic advances.",2019 Feb 26,"['Khan, Meraj A.', 'Ali, Zubair Sabz', 'Sweezey, Neil', 'Grasemann, Hartmut', 'Palaniyar, Nades']",Genes (Basel),,,True
da030e57b186fc870eab92c4f1ac6be717ede6da,PMC,Particulate air pollution on cardiovascular mortality in the tropics: impact on the elderly,http://dx.doi.org/10.1186/s12940-019-0476-4,PMC6471752,30999903,CC BY,"BACKGROUND: Air pollution has a significant health impact. Most data originate from temperate regions. We aim to study the health impact of air pollution, particularly among the elderly, in a tropical region. METHODS: A daily time-series analysis was performed to estimate excess risk (ER) of various air pollutants on daily death counts amongst the general population in Singapore from 2001 to 2013. Air pollutants included particulate matters smaller than 10 μm, and 2.5 μm (PM(10), PM(2.5)), carbon monoxide (CO), nitrogen dioxide (NO(2)), ozone (O(3)) and sulphur dioxide (SO(2)). The studied outcomes were non-accidental and cardiovascular mortality. Single-day lag and distributed lag models were studied and adjusted for confounders. RESULTS: In single-day lag models, a 10 μg/m(3) increase in particulate matter was associated with significant increases in non-accidental (PM(10) ER: 0.627%; 95% confidence interval (CI): 0.260–0.995% and PM(2.5) ER: 0.660%; 95% CI: 0.204–1.118%) and cardiovascular mortality (PM(10) ER: 0.897; 95% CI: 0.283–1.516 and PM(2.5) ER: 0.883%; 95% CI: 0.121–1.621%). This was significant in the elderly ≥ 65 years but not in those < 65 years and were seen in the acute phase of lag 0-5 days. Effects by other pollutants were minimal. For cardiovascular mortality, the effects turned protective at a cumulative lag of 30 days in the elderly and could due to “harvesting”. CONCLUSIONS: These first contemporary population-based data from an equatorial country with tropical climate show that exposure to particulate air pollution was significantly associated with non-accidental mortality and cardiovascular mortality, especially in the elderly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12940-019-0476-4) contains supplementary material, which is available to authorized users.",2019 Apr 18,"['Yap, Jonathan', 'Ng, Yixiang', 'Yeo, Khung Keong', 'Sahlén, Anders', 'Lam, Carolyn Su Ping', 'Lee, Vernon', 'Ma, Stefan']",Environ Health,,,True
d3693cdb4860d66db90f3e6249f4da09033448b1,PMC,Psychometric assessments of Persian translations of three measures of conspiracist beliefs,http://dx.doi.org/10.1371/journal.pone.0215202,PMC6472751,30998716,CC BY,"Several self-report measures of conspiracist beliefs have been developed in Western populations, but examination of their psychometric properties outside Europe and North America is limited. This study aimed to examine the psychometric properties of three widely-used measures of conspiracist beliefs in Iran. We translated the Belief in Conspiracy Theory Inventory (BCTI), Conspiracy Mentality Questionnaire (CMQ), and Generic Conspiracist Belief Scale (GCBS) into Persian. Factorial validity was examined using principal-axis factor analysis in a community sample from Tehran, Iran (N = 544). Further, the relationships between scores on these measures and hypothesized antecedents (i.e., education, schizotypal personality, information processing style, superstitious beliefs, religiosity, and political orientation) were examined. Overall, we failed to find support for the parent factor structures of two of the three scales (BCTI and GCBS) and evidence of construct validity for all three scales was limited. These results highlight the necessity of further psychometric work on existing measures of conspiracy theories in diverse culturo-linguistic groups and the development of context-specific measures of conspiracist beliefs.",2019 Apr 18,"['Atari, Mohammad', 'Afhami, Reza', 'Swami, Viren']",PLoS One,,,True
dbbf1b6713b9819bbe78a272e728951afa62ef95,PMC,Performance and workflow assessment of six nucleic acid extraction technologies for use in resource limited settings,http://dx.doi.org/10.1371/journal.pone.0215753,PMC6472818,30998749,CC0,"Infectious disease nucleic acid amplification technologies (NAAT) have superior sensitivity, specificity, and rapid time to result compared to traditional microbiological methods. Recovery of concentrated, high quality pathogen nucleic acid (NA) from complex specimen matrices is required for optimal performance of several NA amplification/detection technologies such as polymerase chain reaction (PCR). Fully integrated NAAT platforms that enable rapid sample-to-result workflows with minimal user input are generally restricted to larger reference lab settings, and their complexity and cost are prohibitive to widespread implementation in resource limited settings (RLS). Identification of component technologies for incorporation of reliable and affordable sample preparation with pathogen NA amplification/detection into an integrated platform suitable for RLS, is a necessary first step toward achieving the overarching goal of reducing infectious disease-associated morbidity and mortality globally. In the current study, we evaluate the performance of six novel NA extraction technologies from different developers using blinded panels of stool, sputum and blood spiked with variable amounts of quality-controlled DNA- and/or RNA-based microbes. The extraction efficiencies were semi-quantitatively assessed using validated real-time reverse transcription (RT)-PCR assays specific for each microbe and comparing target-specific RT-PCR results to those obtained with reference NA extraction methods. The technologies were ranked based on overall diagnostic accuracy (analytical sensitivity and specificity). Sample input and output volumes, total processing time, user-required manual steps and cost estimates were also examined for suitability in RLS. Together with the performance analysis, these metrics were used to select the more suitable candidate technologies for further optimization of integrated NA amplification and detection technologies for RLS.",2019 Apr 18,"['Beall, Shivani G.', 'Cantera, Jason', 'Diaz, Maureen H.', 'Winchell, Jonas M.', 'Lillis, Lorraine', 'White, Heather', 'Kalnoky, Michael', 'Gallarda, James', 'Boyle, David S.']",PLoS One,,,True
dc8b895c70dc5612cbe0efd328ca21624736c932,PMC,Response Modifiers: Tweaking the Immune Response Against Influenza A Virus,http://dx.doi.org/10.3389/fimmu.2019.00809,PMC6473099,31031778,CC BY,"Despite causing pandemics and yearly epidemics that result in significant morbidity and mortality, our arsenal of options to treat influenza A virus (IAV) infections remains limited and is challenged by the virus itself. While vaccination is the preferred intervention strategy against influenza, its efficacy is reduced in the elderly and infants who are most susceptible to severe and/or fatal infections. In addition, antigenic variation of IAV complicates the production of efficacious vaccines. Similarly, effectiveness of currently used antiviral drugs is jeopardized by the development of resistance to these drugs. Like many viruses, IAV is reliant on host factors and signaling-pathways for its replication, which could potentially offer alternative options to treat infections. While host-factors have long been recognized as attractive therapeutic candidates against other viruses, only recently they have been targeted for development as IAV antivirals. Future strategies to combat IAV infections will most likely include approaches that alter host-virus interactions on the one hand or dampen harmful host immune responses on the other, with the use of biological response modifiers (BRMs). In principle, BRMs are biologically active agents including antibodies, small peptides, and/or other (small) molecules that can influence the immune response. BRMs are already being used in the clinic to treat malignancies and autoimmune diseases. Repurposing such agents would allow for accelerated use against severe and potentially fatal IAV infections. In this review, we will address the potential therapeutic use of different BRM classes to modulate the immune response induced after IAV infections.",2019 Apr 12,"['Elbahesh, Husni', 'Gerlach, Thomas', 'Saletti, Giulietta', 'Rimmelzwaan, Guus F.']",Front Immunol,,,True
4648b12f07c46586cff25b47a85a0f5b6167620e,PMC,Potent Inhibition of Zika Virus Replication by Aurintricarboxylic Acid,http://dx.doi.org/10.3389/fmicb.2019.00718,PMC6473159,31031722,CC BY,"Zika virus (ZIKV) is one of the recently emerging vector-borne viruses in humans and is responsible for severe congenital abnormalities such as microcephaly in the Western Hemisphere. Currently, only a few vaccine candidates and therapeutic drugs are being developed for the treatment of ZIKV infections, and as of yet none are commercially available. The polyanionic aromatic compound aurintricarboxylic acid (ATA) has been shown to have a broad-spectrum antimicrobial and antiviral activity. In this study, we evaluated ATA as a potential antiviral drug against ZIKV replication. The antiviral activity of ATA against ZIKV replication in vitro showed median inhibitory concentrations (IC(50)) of 13.87 ± 1.09 μM and 33.33 ± 1.13 μM in Vero and A549 cells, respectively; without showing any cytotoxic effect in both cell lines (median cytotoxic concentration (CC(50)) > 1,000 μM). Moreover, ATA protected both cell types from ZIKV-induced cytopathic effect (CPE) and apoptosis in a time- and concentration-dependent manner. In addition, pre-treatment of Vero cells with ATA for up to 72 h also resulted in effective suppression of ZIKV replication with similar IC(50). Importantly, the inhibitory effect of ATA on ZIKV infection was effective against strains of the African and Asian/American lineages, indicating that this inhibitory effect was not strain dependent. Overall, these results demonstrate that ATA has potent inhibitory activity against ZIKV replication and may be considered as a potential anti-ZIKV therapy for future clinical evaluation.",2019 Apr 12,"['Park, Jun-Gyu', 'Ávila-Pérez, Ginés', 'Madere, Ferralita', 'Hilimire, Thomas A.', 'Nogales, Aitor', 'Almazán, Fernando', 'Martínez-Sobrido, Luis']",Front Microbiol,,,True
9448084d08566af7477c4611211d1072159b6127,PMC,Bats and Viruses: Emergence of Novel Lyssaviruses and Association of Bats with Viral Zoonoses in the EU,http://dx.doi.org/10.3390/tropicalmed4010031,PMC6473451,30736432,CC BY,"Bats in the EU have been associated with several zoonotic viral pathogens of significance to both human and animal health. Virus discovery continues to expand the existing understating of virus classification, and the increased interest in bats globally as reservoirs or carriers of zoonotic agents has fuelled the continued detection and characterisation of new lyssaviruses and other viral zoonoses. Although the transmission of lyssaviruses from bat species to humans or terrestrial species appears rare, interest in these viruses remains, through their ability to cause the invariably fatal encephalitis—rabies. The association of bats with other viral zoonoses is also of great interest. Much of the EU is free of terrestrial rabies, but several bat species harbor lyssaviruses that remain a risk to human and animal health. Whilst the rabies virus is the main cause of rabies globally, novel related viruses continue to be discovered, predominantly in bat populations, that are of interest purely through their classification within the lyssavirus genus alongside the rabies virus. Although the rabies virus is principally transmitted from the bite of infected dogs, these related lyssaviruses are primarily transmitted to humans and terrestrial carnivores by bats. Even though reports of zoonotic viruses from bats within the EU are rare, to protect human and animal health, it is important characterise novel bat viruses for several reasons, namely: (i) to investigate the mechanisms for the maintenance, potential routes of transmission, and resulting clinical signs, if any, in their natural hosts; (ii) to investigate the ability of existing vaccines, where available, to protect against these viruses; (iii) to evaluate the potential for spill over and onward transmission of viral pathogens in novel terrestrial hosts. This review is an update on the current situation regarding zoonotic virus discovery within bats in the EU, and provides details of potential future mechanisms to control the threat from these deadly pathogens.",2019 Feb 7,"['Shipley, Rebecca', 'Wright, Edward', 'Selden, David', 'Wu, Guanghui', 'Aegerter, James', 'Fooks, Anthony R', 'Banyard, Ashley C']",Trop Med Infect Dis,,,True
d13f5a5fa79315e120154fcac023f97ccfe8ad6f,PMC,Sources of Type I Interferons in Infectious Immunity: Plasmacytoid Dendritic Cells Not Always in the Driver's Seat,http://dx.doi.org/10.3389/fimmu.2019.00778,PMC6473462,31031767,CC BY,"Type I Interferons (IFNs) are hallmark cytokines produced in immune responses to all classes of pathogens. Type I IFNs can influence dendritic cell (DC) activation, maturation, migration, and survival, but also directly enhance natural killer (NK) and T/B cell activity, thus orchestrating various innate and adaptive immune effector functions. Therefore, type I IFNs have long been considered essential in the host defense against virus infections. More recently, it has become clear that depending on the type of virus and the course of infection, production of type I IFN can also lead to immunopathology or immunosuppression. Similarly, in bacterial infections type I IFN production is often associated with detrimental effects for the host. Although most cells in the body are thought to be able to produce type I IFN, plasmacytoid DCs (pDCs) have been termed the natural “IFN producing cells” due to their unique molecular adaptations to nucleic acid sensing and ability to produce high amounts of type I IFN. Findings from mouse reporter strains and depletion experiments in in vivo infection models have brought new insights and established that the role of pDCs in type I IFN production in vivo is less important than assumed. Production of type I IFN, especially the early synthesized IFNβ, is rather realized by a variety of cell types and cannot be mainly attributed to pDCs. Indeed, the cell populations responsible for type I IFN production vary with the type of pathogen, its tissue tropism, and the route of infection. In this review, we summarize recent findings from in vivo models on the cellular source of type I IFN in different infectious settings, ranging from virus, bacteria, and fungi to eukaryotic parasites. The implications from these findings for the development of new vaccination and therapeutic designs targeting the respectively defined cell types are discussed.",2019 Apr 12,"['Ali, Shafaqat', 'Mann-Nüttel, Ritu', 'Schulze, Anja', 'Richter, Lisa', 'Alferink, Judith', 'Scheu, Stefanie']",Front Immunol,,,True
4b14a22f5d87d81ad62ea7fff06042d8dc071f28,PMC,P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages,http://dx.doi.org/10.3389/fimmu.2019.00786,PMC6473476,31031770,CC BY,"Chikungunya virus (CHIKV), a mosquito-borne Alphavirus, is endemic in different parts of the globe. The host macrophages are identified as the major cellular reservoirs of CHIKV during infection and this virus triggers robust TNF production in the host macrophages, which might be a key mediator of virus induced inflammation. However, the molecular mechanism underneath TNF induction is not understood yet. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV to address the above-mentioned question. It was observed that CHIKV induces both p38 and JNK phosphorylation in macrophages in a time-dependent manner and p-p38 inhibitor, SB203580 is effective in reducing infection even at lower concentration as compared to the p-JNK inhibitor, SP600125. However, inhibition of p-p38 and p-JNK decreased CHIKV induced TNF production in the host macrophages. Moreover, CHIKV induced macrophage derived TNF was found to facilitate TCR driven T cell activation. Additionally, it was noticed that the expressions of key transcription factors involved mainly in antiviral responses (p-IRF3) and TNF production (p-c-jun) were induced significantly in the CHIKV infected macrophages as compared to the corresponding mock cells. Further, it was demonstrated that CHIKV mediated TNF production in the macrophages is dependent on p38 and JNK MAPK pathways linking p-c-jun transcription factor. Interestingly, it was found that CHIKV nsP2 interacts with both p-p38 and p-JNK MAPKs in the macrophages. This observation was supported by the in silico protein-protein docking analysis which illustrates the specific amino acids responsible for the nsP2-MAPKs interactions. A strong polar interaction was predicted between Thr-180 (within the phosphorylation lip) of p38 and Gln-273 of nsP2, whereas, no such polar interaction was predicted for the phosphorylation lip of JNK which indicates the differential roles of p-p38 and p-JNK during CHIKV infection in the host macrophages. In summary, for the first time it has been shown that CHIKV triggers robust TNF production in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and the interaction of viral protein, nsP2 with these MAPKs during infection. Hence, this information might shed light in rationale-based drug designing strategies toward a possible control measure of CHIKV infection in future.",2019 Apr 12,"['Nayak, Tapas Kumar', 'Mamidi, Prabhudutta', 'Sahoo, Subhransu Sekhar', 'Kumar, P. Sanjai', 'Mahish, Chandan', 'Chatterjee, Sanchari', 'Subudhi, Bharat Bhusan', 'Chattopadhyay, Soma', 'Chattopadhyay, Subhasis']",Front Immunol,,,False
196d55353760e8e1ddbc2e2cce92f806351b747c,PMC,P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages,http://dx.doi.org/10.3389/fimmu.2019.00786,PMC6473476,31031770,CC BY,"Chikungunya virus (CHIKV), a mosquito-borne Alphavirus, is endemic in different parts of the globe. The host macrophages are identified as the major cellular reservoirs of CHIKV during infection and this virus triggers robust TNF production in the host macrophages, which might be a key mediator of virus induced inflammation. However, the molecular mechanism underneath TNF induction is not understood yet. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV to address the above-mentioned question. It was observed that CHIKV induces both p38 and JNK phosphorylation in macrophages in a time-dependent manner and p-p38 inhibitor, SB203580 is effective in reducing infection even at lower concentration as compared to the p-JNK inhibitor, SP600125. However, inhibition of p-p38 and p-JNK decreased CHIKV induced TNF production in the host macrophages. Moreover, CHIKV induced macrophage derived TNF was found to facilitate TCR driven T cell activation. Additionally, it was noticed that the expressions of key transcription factors involved mainly in antiviral responses (p-IRF3) and TNF production (p-c-jun) were induced significantly in the CHIKV infected macrophages as compared to the corresponding mock cells. Further, it was demonstrated that CHIKV mediated TNF production in the macrophages is dependent on p38 and JNK MAPK pathways linking p-c-jun transcription factor. Interestingly, it was found that CHIKV nsP2 interacts with both p-p38 and p-JNK MAPKs in the macrophages. This observation was supported by the in silico protein-protein docking analysis which illustrates the specific amino acids responsible for the nsP2-MAPKs interactions. A strong polar interaction was predicted between Thr-180 (within the phosphorylation lip) of p38 and Gln-273 of nsP2, whereas, no such polar interaction was predicted for the phosphorylation lip of JNK which indicates the differential roles of p-p38 and p-JNK during CHIKV infection in the host macrophages. In summary, for the first time it has been shown that CHIKV triggers robust TNF production in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and the interaction of viral protein, nsP2 with these MAPKs during infection. Hence, this information might shed light in rationale-based drug designing strategies toward a possible control measure of CHIKV infection in future.",2019 Apr 12,"['Nayak, Tapas Kumar', 'Mamidi, Prabhudutta', 'Sahoo, Subhransu Sekhar', 'Kumar, P. Sanjai', 'Mahish, Chandan', 'Chatterjee, Sanchari', 'Subudhi, Bharat Bhusan', 'Chattopadhyay, Soma', 'Chattopadhyay, Subhasis']",Front Immunol,,,True
caef06c4bfe01781e8efcb9d5d22a1f5d5b2efc0,PMC,Endemic Melioidosis in Southern China: Past and Present,http://dx.doi.org/10.3390/tropicalmed4010039,PMC6473618,30823573,CC BY,"Melioidosis is a severe tropical infectious disease caused by the soil-dwelling bacterium Burkholderia pseudomallei, predominantly endemic to Southeast Asia and northern Australia. Between the 1970s and the 1990s, the presence of B. pseudomallei causing melioidosis in humans and other animals was demonstrated in four coastal provinces in southern China: Hainan, Guangdong, Guangxi, and Fujian, although indigenous cases were rare and the disease failed to raise concern amongst local and national health authorities. In recent years, there has been a rise in the number of melioidosis cases witnessed in the region, particularly in Hainan. Meanwhile, although China has established and maintained an effective communicable disease surveillance system, it has not yet been utilized for melioidosis. Thus, the overall incidence, social burden and epidemiological features of the disease in China remain unclear. In this context, we present a comprehensive overview of both historical and current information on melioidosis in Southern China, highlighting the re-emergence of the disease in Hainan. Surveillance and management strategies for melioidosis should be promoted in mainland China, and more research should be conducted to provide further insights into the present situation.",2019 Feb 25,"['Zheng, Xiao', 'Xia, Qianfeng', 'Xia, Lianxu', 'Li, Wei']",Trop Med Infect Dis,,,True
656d6ea3a8c6f4ec9bd039b04262a558fa9ca557,PMC,Endemic Melioidosis in Southern China: Past and Present,http://dx.doi.org/10.3390/tropicalmed4010039,PMC6473618,30823573,CC BY,"Melioidosis is a severe tropical infectious disease caused by the soil-dwelling bacterium Burkholderia pseudomallei, predominantly endemic to Southeast Asia and northern Australia. Between the 1970s and the 1990s, the presence of B. pseudomallei causing melioidosis in humans and other animals was demonstrated in four coastal provinces in southern China: Hainan, Guangdong, Guangxi, and Fujian, although indigenous cases were rare and the disease failed to raise concern amongst local and national health authorities. In recent years, there has been a rise in the number of melioidosis cases witnessed in the region, particularly in Hainan. Meanwhile, although China has established and maintained an effective communicable disease surveillance system, it has not yet been utilized for melioidosis. Thus, the overall incidence, social burden and epidemiological features of the disease in China remain unclear. In this context, we present a comprehensive overview of both historical and current information on melioidosis in Southern China, highlighting the re-emergence of the disease in Hainan. Surveillance and management strategies for melioidosis should be promoted in mainland China, and more research should be conducted to provide further insights into the present situation.",2019 Feb 25,"['Zheng, Xiao', 'Xia, Qianfeng', 'Xia, Lianxu', 'Li, Wei']",Trop Med Infect Dis,,,False
5a4fe515ba7441d9da4fd72539d9c525b8c7b0b3,PMC,Differentiating Rhinitis in the Paediatric Population by Giving Focus on Medical History and Clinical Examination,http://dx.doi.org/10.3390/medsci7030038,PMC6473768,30813653,CC BY,"Chronic rhinitis is defined as an inflammation of the nasal epithelium, and is characterized by the presence of two or more specific nasal symptoms including obstruction, rhinorrhea, sneezing, and/or itching for at least 12 weeks. In childhood, this clinical entity is very common and carries a significant socioeconomic burden. The impact on the physical, social, and psychological well-being of family cannot be underestimated. Rhinitis is an umbrella term which includes different phenotypes of rhinitis with distinct underlying pathophysiologic mechanisms. In most cases the diagnosis of rhinitis is rather straightforward; however, sometimes when based on clinical symptomatology, characterization may be challenging. Herein, we provide guidance for getting all the data needed for the differential diagnosis of rhinitis based on medical history and clinical examination.",2019 Feb 26,"['Doulaptsi, Maria', 'Aoi, Noriaki', 'Kawauchi, Hideyuki', 'Milioni, Athanasia', 'Karatzanis, Alexander', 'Prokopakis, Emmanuel']",Med Sci (Basel),,,True
95cc317541d97e3dbaa1662894fdbed842098910,PMC,Potential Intermediate Hosts for Coronavirus Transmission: No Evidence of Clade 2c Coronaviruses in Domestic Livestock from Ghana,http://dx.doi.org/10.3390/tropicalmed4010034,PMC6473935,30744201,CC BY,"The emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV), nearly a decade ago with worldwide distribution, was believed to be of zoonotic origin from bats with dromedary camels as intermediate hosts. There is a likelihood of other domestic livestock serving as intermediate hosts for this virus. The presence of coronaviruses, closely related to MERS-CoV in Ghanaian bats, presented the opportunity to test the hypothesis of transmissibility of this virus through domestic livestock species. The possible interactions between livestock and bats in 31 household farms were accessed by observation and interviews with farmers. Rectal swabs and serum from cattle, sheep, goats, donkeys, and swine from commercial and household farms were tested for MERS-CoV and a Nycteris sp. bat coronavirus, previously detected in Ghana. A pan-PCR assay to detect clade 2c viruses and recombinant immunofluorescence assay to detect anti-spike IgG antibodies against the target viruses were used. Likely contact between livestock and bats was determined for 13 farms (41.9%) that reported confining their livestock and also observing bats in their homes. Livestock were left unconfined on eight farms (25.8%) that also observed bats roosting in trees close to their homes. No viral RNA or antibodies against the two coronaviruses were detected in any of the livestock species tested. Cattle, sheep, goats, donkeys, and swine are not likely hosts of clade 2c coronaviruses.",2019 Feb 10,"['El-Duah, Philip', 'Sylverken, Augustina', 'Owusu, Michael', 'Yeboah, Richmond', 'Lamptey, Jones', 'Oppong Frimpong, Yaw', 'Burimuah, Vitus', 'Antwi, Christopher', 'Folitse, Raphael', 'Agbenyega, Olivia', 'Oppong, Samuel', 'Adu-Sarkodie, Yaw']",Trop Med Infect Dis,,,True
7d474a83f0555f291283b0a3c9a86aced880cfe9,PMC,Cloning and characterization of a tyrosine decarboxylase involved in the biosynthesis of galanthamine in Lycoris aurea,http://dx.doi.org/10.7717/peerj.6729,PMC6474336,31024762,CC BY,"BACKGROUND: Galanthamine, one kind of Amaryllidaceae alkaloid extracted from the Lycoris species, is used in the treatment of Alzheimer’s disease. In regards to medical and economic importance, the biosynthesis and regulatory mechanism of the secondary metabolites in Lycoris remain uninvestigated. METHODS: BLAST was used to identify the sequence of tyrosine decarboxylase in the transcriptome of Lycoris aurea (L’Hér) Herb. The enzyme activity of this TYDC was determined by using heterologous expressed protein in the Escherichia coli cells. The related productive contents of tyramine were detected using High Performance Liquid Chromatography (HPLC). According to the available micro RNA sequencing profiles and degradome database of L. aurea, microRNA396 were isolated, which targets to LaTYDC1 and RNA Ligase-Mediated-Rapid Amplification of cDNA Ends (RLM-RACE) were used to confirm the cleavage. The expression levels of miR396 and LaTYDC1 were measured using a quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: LaTYDC1 was mainly expressed in root, bulb, leaf and flower fitting the models for galanthamine accumulation. This decarboxylase efficiently catalyzes tyrosine to tyramine conversion. Under methyl jasmonate (MeJA) treatment, the expression of LaTYDC1 and the content of tyramine sharply increase. The use of RLM-RACE confirms that miR396 promotes the degradation of LaTYDC1 mRNA. Under MeJA treatment, the expression of miR396 was suppressed while the expression level of LaTYDC1 sharply increased. Following the increase of the miR396 transcriptional level, LaTYDC1 was significantly repressed. CONCLUSION: LaTYDC1 participates in the biosynthesis of galanthamine, and is regulated by miR396. This finding also provides genetic strategy for improving the yield of galanthamine in the future.",2019 Apr 16,"['Wang, Rong', 'Han, Xiaokang', 'Xu, Sheng', 'Xia, Bing', 'Jiang, Yumei', 'Xue, Yong', 'Wang, Ren']",PeerJ,,,False
19bbeefa3a126f32fe8339a1fb11e3d9a1c7881c,PMC,How host genetics dictates successful viral zoonosis,http://dx.doi.org/10.1371/journal.pbio.3000217,PMC6474636,31002666,CC BY,"Viruses of wild and domestic animals can infect humans in a process called zoonosis, and these events can give rise to explosive epidemics such as those caused by the HIV and Ebola viruses. While humans are constantly exposed to animal viruses, those that can successfully infect and transmit between humans are exceedingly rare. The key event in zoonosis is when an animal virus begins to replicate (one virion making many) in the first human subject. Only at this point will the animal virus first experience the selective environment of the human body, rendering possible viral adaptation and refinement for humans. In addition, appreciable viral titers in this first human may enable infection of a second, thus initiating selection for viral variants with increased capacity for spread. We assert that host genetics plays a critical role in defining which animal viruses in nature will achieve this key event of replication in a first human host. This is because animal viruses that pose the greatest risk to humans will have few (or no) genetic barriers to replicating themselves in human cells, thus requiring minimal mutations to make this jump. Only experimental virology provides a path to identifying animal viruses with the potential to replicate themselves in humans because this information will not be evident from viral sequencing data alone.",2019 Apr 19,"['Warren, Cody J.', 'Sawyer, Sara L.']",PLoS Biol,,,True
ac5b22cca25686b387a8ea806008de5d8e41bd55,PMC,Human metapneumovirus activates NOD-like receptor protein 3 inflammasome via its small hydrophobic protein which plays a detrimental role during infection in mice,http://dx.doi.org/10.1371/journal.ppat.1007689,PMC6474638,30964929,CC BY,"NOD-like receptor protein 3 (NLRP3) inflammasome activation triggers caspase-1 activation-induced maturation of interleukin (IL)-1β and IL-18 and therefore is important for the development of the host defense against various RNA viral diseases. However, the implication of this protein complex in human metapneumovirus (HMPV) disease has not been fully studied. Herein, we report that NLRP3 inflammasome plays a detrimental role during HMPV infection because NLRP3 inflammasome inhibition protected mice from mortality and reduced weight loss and inflammation without impacting viral replication. We also demonstrate that NLRP3 inflammasome exerts its deleterious effect via IL-1β production since we observed reduced mortality, weight loss and inflammation in IL-1β-deficient (IL-1β(-/-)) mice, as compared to wild-type animals during HMPV infection. Moreover, the effect on these evaluated parameters was not different in IL-1β(-/-) and wild-type mice treated with an NLRP3 inflammasome inhibitor. The production of IL-1β was also abrogated in bone marrow derived macrophages deficient for NLRP3. Finally, we show that small hydrophobic protein-deleted recombinant HMPV (HMPV ΔSH) failed to activate caspase-1, which is responsible for IL-1β cleavage and maturation. Furthermore, HMPV ΔSH-infected mice had less weight loss, showed no mortality and reduced inflammation, as compared to wild-type HMPV-infected mice. Thus, NLRP3 inflammasome activation seems to be triggered by HMPV SH protein in HMPV disease. In summary, once activated by the HMPV SH protein, NLRP3 inflammasome promotes the maturation of IL-1β, which exacerbates HMPV-induced inflammation. Therefore, the blockade of IL-1β production by using NLRP3 inflammasome inhibitors might be a novel potential strategy for the therapy and prevention of HMPV infection.",2019 Apr 9,"['Lê, Vuong B.', 'Dubois, Julia', 'Couture, Christian', 'Cavanagh, Marie-Hélène', 'Uyar, Olus', 'Pizzorno, Andres', 'Rosa-Calatrava, Manuel', 'Hamelin, Marie-Ève', 'Boivin, Guy']",PLoS Pathog,,,True
24beb94c313a07be6b0c745a6ca8a3d810618506,PMC,Immunogenicity of Different Forms of Middle East Respiratory Syndrome S Glycoprotein,,PMC6475872,31024747,CC BY,"The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreaks. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~35.5%. Currently, there are no registered vaccines or means of therapeutic protection against MERS in the world. The MERS-CoV S glycoprotein plays the most important role in the viral life cycle (virus internalization). The S protein is an immunodominant antigen and the main target for neutralizing antibodies. In the present study, the immunogenicities of five different forms of the MERS-CoV S glycoprotein were compared: the full-length S glycoprotein, the full-length S glycoprotein with the transmembrane domain of the G glycoprotein of VSV (S-G), the receptor-binding domain (RBD) of the S glycoprotein, the membrane-fused RBD (the RBD fused with the transmembrane domain of the VSV G glycoprotein (RBD-G)), and the RBD fused with Fc of human IgG1 (RBD-Fc). Recombinant vectors based on human adenoviruses type 5 (rAd5) were used as delivery vehicles. Vaccination with all of the developed rAd5 vectors elicited a balanced Th1/Th2 response in mice. The most robust humoral immune response was induced after the animal had been vaccinated with the membrane-fused RBD (rAd5-RBD-G). Only immunization with membrane forms of the glycoprotein (rAd5-S, rAd5-S-G, and rAd5-RBD-G) elicited neutralizing antibodies among all vaccinated animals. The most significant cellular immune response was induced after vaccination of the animals with the full-length S (rAd5-S). These investigations suggest that the full-length S and the membrane form of the RBD (RBD-G) are the most promising vaccine candidates among all the studied forms of S glycoprotein.",2019 Jan-Mar,"['Ozharovskaia, T. A.', 'Zubkova, O. V.', 'Dolzhikova, I. V.', 'Gromova, A. S.', 'Grousova, D. M.', 'Tukhvatulin, A. I.', 'Popova, O.', 'Shcheblyakov, D. V.', 'Scherbinin, D. N.', 'Dzharullaeva, A. S.', 'Erokhova, A. S.', 'Shmarov, M. M.', 'Loginova, S. Y.', 'Borisevich, S. V.', 'Naroditsky, B. S.', 'Logunov, D. Y.', 'Gintsburg, A. L.']",Acta Naturae,,,True
c4a42dab0e3e471c7a54410c8ddfee13741df4aa,PMC,Exercise in Glucose-6-Phosphate Dehydrogenase Deficiency: Harmful or Harmless? A Narrative Review,http://dx.doi.org/10.1155/2019/8060193,PMC6476018,31089417,CC BY,"OBJECTIVES: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, theoretically, renders red blood cells (RBC) susceptible to oxidative stress. G6PD deficiency has also been found in other types of cells than RBC, such as leukocytes and myocytes, where an inefficient protection against oxidative stress may occur too. Glutathione (GSH), a significant antioxidant molecule, levels are lower in G6PD individuals, and theoretically, the probability of oxidative stress and haemolysis due to exercise in individuals with G6PD deficiency is increased, whereas dietary supplementation with antioxidants may have beneficial effects on various aspects of this enzymopathy. METHODS: A search of the available literature was conducted using the keywords glucose-6-phosphate dehydrogenase (G6PD), deficiency, disease, exercise, muscle, antioxidant, vitamin, supplement, and supplementation. The search was limited to publications in English, conducted on humans, and published until August 2018. After screening, only relevant articles were included. RESULTS: There is little evidence indicating that G6PD deficiency can cause perturbations in redox status, haemolysis, and clinical symptoms such as fatigability and myoglobinuria, especially after intense exercise, compared to individuals with normal enzyme levels. CONCLUSIONS: Exercise could be used by G6PD-deficient individuals as a tool to improve their quality of life. However, there is a lack of training studies, and assessment of the effects of regular and systematic exercise in G6PD-deficient individuals is warranted. Finally, since GSH levels are lower in G6PD deficiency, it would be interesting to examine the effects of antioxidant or cysteine donor supplements on redox status after exercise in these individuals.",2019 Apr 4,"['Georgakouli, Kalliopi', 'Fatouros, Ioannis G.', 'Draganidis, Dimitrios', 'Papanikolaou, Konstantinos', 'Tsimeas, Panagiotis', 'Deli, Chariklia K.', 'Jamurtas, Athanasios Z.']",Oxid Med Cell Longev,,,True
3f8beb2781bb92d1e2fffd8361b1feec3fd834e9,PMC,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Infection, Immunological Response, and Vaccine Development",http://dx.doi.org/10.1155/2019/6491738,PMC6476043,31089478,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in late 2012. Since its emergence, a total of 2279 patients from 27 countries have been infected across the globe according to a World Health Organization (WHO) report (Feb. 12th, 2019). Approximately 806 patients have died. The virus uses its spike proteins as adhesive factors that are proinflammatory for host entry through a specific receptor called dipeptidyl peptidase-4 (DPP4). This receptor is considered a key factor in the signaling and activation of the acquired and innate immune responses in infected patients. Using potent antigens in combination with strong adjuvants may effectively trigger the activation of specific MERS-CoV cellular responses as well as the production of neutralizing antibodies. Unfortunately, to date, there is no effective approved treatment or vaccine for MERS-CoV. Thus, there are urgent needs for the development of novel MERS-CoV therapies as well as vaccines to help minimize the spread of the virus from infected patients, thereby mitigating the risk of any potential pandemics. Our main goals are to highlight and describe the current knowledge of both the innate and adaptive immune responses to MERS-CoV and the current state of MERS-CoV vaccine development. We believe this study will increase our understanding of the mechanisms that enhance the MERS-CoV immune response and subsequently contribute to the control of MERS-CoV infections.",2019 Apr 7,"['Mubarak, Ayman', 'Alturaiki, Wael', 'Hemida, Maged Gomaa']",J Immunol Res,,,True
3ffa62baea2f955470dff08e4d5e157ce0e28cc0,PMC,Strategies in regulating glioblastoma signaling pathways and anti-invasion therapy,http://dx.doi.org/10.1371/journal.pone.0215547,PMC6476530,31009513,CC BY,"Glioblastoma multiforme is one of the most invasive type of glial tumors, which rapidly grows and commonly spreads into nearby brain tissue. It is a devastating brain cancer that often results in death within approximately 12 to 15 months after diagnosis. In this work, optimal control theory was applied to regulate intracellular signaling pathways of miR-451–AMPK–mTOR–cell cycle dynamics via glucose and drug intravenous administration infusions. Glucose level is controlled to activate miR-451 in the up-stream pathway of the model. A potential drug blocking the inhibitory pathway of mTOR by AMPK complex is incorporated to explore regulation of the down-stream pathway to the cell cycle. Both miR-451 and mTOR levels are up-regulated inducing cell proliferation and reducing invasion in the neighboring tissues. Concomitant and alternating glucose and drug infusions are explored under various circumstances to predict best clinical outcomes with least administration costs.",2019 Apr 22,"['Jung, Eunok', 'de los Reyes V, Aurelio A.', 'Pumares, Kurt Jan A.', 'Kim, Yangjin']",PLoS One,,,True
ca263a715caad1f66d07a2aa191154fafbfbe67a,PMC,Strategies in regulating glioblastoma signaling pathways and anti-invasion therapy,http://dx.doi.org/10.1371/journal.pone.0215547,PMC6476530,31009513,CC BY,"Glioblastoma multiforme is one of the most invasive type of glial tumors, which rapidly grows and commonly spreads into nearby brain tissue. It is a devastating brain cancer that often results in death within approximately 12 to 15 months after diagnosis. In this work, optimal control theory was applied to regulate intracellular signaling pathways of miR-451–AMPK–mTOR–cell cycle dynamics via glucose and drug intravenous administration infusions. Glucose level is controlled to activate miR-451 in the up-stream pathway of the model. A potential drug blocking the inhibitory pathway of mTOR by AMPK complex is incorporated to explore regulation of the down-stream pathway to the cell cycle. Both miR-451 and mTOR levels are up-regulated inducing cell proliferation and reducing invasion in the neighboring tissues. Concomitant and alternating glucose and drug infusions are explored under various circumstances to predict best clinical outcomes with least administration costs.",2019 Apr 22,"['Jung, Eunok', 'de los Reyes V, Aurelio A.', 'Pumares, Kurt Jan A.', 'Kim, Yangjin']",PLoS One,,,False
48215f45ce10b06c8f96b087cf1d72de2b40662a,PMC,Dichloro-Phenyl-Benzotriazoles: A New Selective Class of Human Respiratory Syncytial Virus Entry Inhibitors,http://dx.doi.org/10.3389/fchem.2019.00247,PMC6476926,31041309,CC BY,"Human Respiratory Syncytial Virus (RSV) is the primary cause of bronchopneumonia in infants and children worldwide. Clinical studies have shown that early treatments of RSV patients with ribavirin improve prognosis, even if the use of this drug is limited due to myelosuppression and toxicity effects. Furthermore, effective vaccines to prevent RSV infection are currently unavailable. Thus, the development of highly effective and specific antiviral drugs for pre-exposure prophylaxis and/or treatment of RSV infections is a compelling need. In the quest of new RSV inhibitors, in this work we evaluated the antiviral activity of a series of variously substituted 5,6-dichloro-1-phenyl-1(2)H-benzo[d][1,2,3]triazole derivatives in cell-based assays. Several 1- and 2-phenyl-benzotriazoles resulted fairly potent (μM concentrations) inhibitors of RSV infection in plaque reduction assays, accompanied by low cytotoxicity in human highly dividing T lymphoid-derived cells and primary cell lines. Contextually, no inhibitory effects were observed against other RNA or DNA viruses assayed, suggesting specific activity against RSV. Further results revealed that the lead compound 10d was active during the early phase of the RSV infection cycle. To understand whether 10d interfered with virus attachment to target cells or virus-cell fusion events, inhibitory activity tests against the RSV mutant strain B1 cp-52—expressing only the F envelope glycoprotein—and a plasmid-based reporter assay that quantifies the bioactivity of viral entry were also performed. The overall biological results, in conjunction with in silico modeling studies, supported the conclusion that the RSV fusion process could be the target of this new series of compounds.",2019 Apr 16,"['Piras, Sandra', 'Sanna, Giuseppina', 'Carta, Antonio', 'Corona, Paola', 'Ibba, Roberta', 'Loddo, Roberta', 'Madeddu, Silvia', 'Caria, Paola', 'Aulic, Suzana', 'Laurini, Erik', 'Fermeglia, Maurizio', 'Pricl, Sabrina']",Front Chem,,,True
97e4ef6563c15d0a2291272e99cdc11dd4c02134,PMC,Faster recovery and reduced paracetamol use – a meta-analysis of EPs 7630 in children with acute respiratory tract infections,http://dx.doi.org/10.1186/s12887-019-1473-z,PMC6477747,31014293,CC BY,"OBJECTIVE: Fever is a very common adaptive immune response in acute respiratory tract disorders during infancy. Antipyretic / analgesic drugs such as paracetamol (acetaminophen) are widely used to improve the comfort of the child but may cause medically unneeded antipyresis and rare but potentially serious side effects. We assess whether treatment with Pelargonium sidoides extract EPs 7630 reduces the administration of paracetamol in children with acute tonsillopharyngitis (ATP) or acute bronchitis (AB). DESIGN: Meta-analysis of randomised, placebo-controlled clinical trials. METHODS: We searched clinical trial registries (ISRCTN, ClinicalTrials.gov) and medical literature (MEDLINE, EMBASE), for randomised, placebo-controlled trials investigating the administration of EPs 7630 to children with ATP or AB and reporting the co-administration of paracetamol. Based on the individual participant data of the eligible trials, study populations were characterized according to sex and age, and meta-analyses were performed for cumulative paracetamol use and ability to attend school at treatment end. RESULTS: Six trials including a total of 523 children aged 6–10 years (EPs 7630: 265; placebo: 258) and suffering from non-β-hemolytic streptococcal ATP (3 trials) or from AB (3 trials) were identified and eligible. Children received EPs 7630 or placebo for 6 (ATP) or 7 days (AB). Compared to placebo, EPs 7630 reduced the cumulative dose of paracetamol in 5 out of the 6 trials, by an average of 244 mg (Hedges’ g; − 0.28; 95% confidence interval: [− 0.53; − 0.02]; p < 0.03). At treatment end, 30.2% (EPs 7630) and 74.4% (placebo) of the children were still unable to attend school (risk ratio: 0.43; 95% confidence interval: [0.29; 0.65]; p < 0.001). CONCLUSIONS: In children aged 6–10 years with AB or ATP, EPs 7630 alleviated the symptom burden and accelerated recovery. Although EPs 7630 has no known antipyretic effect, concomitant use of paracetamol was reduced.",2019 Apr 23,"['Seifert, Georg', 'Brandes-Schramm, Juliette', 'Zimmermann, Andrea', 'Lehmacher, Walter', 'Kamin, Wolfgang']",BMC Pediatr,,,True
147b848766e7280950bd8ac4d1c02efb55e63ef3,PMC,Consensus and variations in cell line specificity among human metapneumovirus strains,http://dx.doi.org/10.1371/journal.pone.0215822,PMC6478314,31013314,CC BY,"Human metapneumovirus (HMPV) has been a notable etiological agent of acute respiratory infection in humans, but it was not discovered until 2001, because HMPV replicates only in a limited number of cell lines and the cytopathic effect (CPE) is often mild. To promote the study of HMPV, several groups have generated green fluorescent protein (GFP)-expressing recombinant HMPV strains (HMPV(GFP)). However, the growing evidence has complicated the understanding of cell line specificity of HMPV, because it seems to vary notably among HMPV strains. In addition, unique A2b clade HMPV strains with a 180-nucleotide duplication in the G gene (HMPV A2b(180nt-dup) strains) have recently been detected. In this study, we re-evaluated and compared the cell line specificity of clinical isolates of HMPV strains, including the novel HMPV A2b(180nt-dup) strains, and six recombinant HMPV(GFP) strains, including the newly generated recombinant HMPV A2b(180nt-dup) strain, MG0256-EGFP. Our data demonstrate that VeroE6 and LLC-MK2 cells generally showed the highest infectivity with any clinical isolates and recombinant HMPV(GFP) strains. Other human-derived cell lines (BEAS-2B, A549, HEK293, MNT-1, and HeLa cells) showed certain levels of infectivity with HMPV, but these were significantly lower than those of VeroE6 and LLC-MK2 cells. Also, the infectivity in these suboptimal cell lines varied greatly among HMPV strains. The variations were not directly related to HMPV genotypes, cell lines used for isolation and propagation, specific genome mutations, or nucleotide duplications in the G gene. Thus, these variations in suboptimal cell lines are likely intrinsic to particular HMPV strains.",2019 Apr 23,"['Nao, Naganori', 'Sato, Ko', 'Yamagishi, Junya', 'Tahara, Maino', 'Nakatsu, Yuichiro', 'Seki, Fumio', 'Katoh, Hiroshi', 'Ohnuma, Aiko', 'Shirogane, Yuta', 'Hayashi, Masahiro', 'Suzuki, Tamio', 'Kikuta, Hideaki', 'Nishimura, Hidekazu', 'Takeda, Makoto']",PLoS One,,,True
40cf1b3081095810f3ea2fe14764071d3c1c1c65,PMC,Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR),http://dx.doi.org/10.1128/mBio.00668-19,PMC6479006,31015330,CC BY,"Protein kinase R (PKR) plays a major role in activating host immunity during infection by sensing double-stranded RNA (dsRNA) produced by viruses. Once activated by dsRNA, PKR phosphorylates the translation factor eukaryotic initiation factor 2α (eIF2α), halting cellular translation. Many viruses have methods of inhibiting PKR activation or its downstream effects, circumventing protein synthesis shutdown. These include sequestering dsRNA or producing proteins that bind to and inhibit PKR activation. Here we describe our finding that in multiple cell types, PKR was depleted during mouse adenovirus type 1 (MAV-1) infection. MAV-1 did not appear to be targeting PKR at the transcriptional or translational level, because total PKR mRNA levels and levels of PKR mRNA bound to polysomes were unchanged or increased during MAV-1 infection. However, inhibiting the proteasome reduced the PKR depletion seen in MAV-1-infected cells, whereas inhibiting the lysosome had no effect. This suggests that proteasomal degradation alone is responsible for PKR degradation during MAV-1 infection. Time course experiments indicated that the degradation occurs early after infection. Infecting cells with UV-inactivated virus prevented PKR degradation, whereas inhibiting viral DNA replication did not. Together, these results suggest that an early viral gene is responsible. Degradation of PKR is a rare mechanism to oppose PKR activity, and it has been described in only six RNA viruses. To our knowledge, this is the first example of a DNA virus counteracting PKR by degrading it.",2019 Apr 23,"['Goodman, Danielle E.', 'Pretto, Carla D.', 'Krepostman, Tomas A.', 'Carnahan, Kelly E.', 'Spindler, Katherine R.']",mBio,,,True
fece2a0984edf04d038f80b5cd652dad8c6a0fec,PMC,Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR),http://dx.doi.org/10.1128/mBio.00668-19,PMC6479006,31015330,CC BY,"Protein kinase R (PKR) plays a major role in activating host immunity during infection by sensing double-stranded RNA (dsRNA) produced by viruses. Once activated by dsRNA, PKR phosphorylates the translation factor eukaryotic initiation factor 2α (eIF2α), halting cellular translation. Many viruses have methods of inhibiting PKR activation or its downstream effects, circumventing protein synthesis shutdown. These include sequestering dsRNA or producing proteins that bind to and inhibit PKR activation. Here we describe our finding that in multiple cell types, PKR was depleted during mouse adenovirus type 1 (MAV-1) infection. MAV-1 did not appear to be targeting PKR at the transcriptional or translational level, because total PKR mRNA levels and levels of PKR mRNA bound to polysomes were unchanged or increased during MAV-1 infection. However, inhibiting the proteasome reduced the PKR depletion seen in MAV-1-infected cells, whereas inhibiting the lysosome had no effect. This suggests that proteasomal degradation alone is responsible for PKR degradation during MAV-1 infection. Time course experiments indicated that the degradation occurs early after infection. Infecting cells with UV-inactivated virus prevented PKR degradation, whereas inhibiting viral DNA replication did not. Together, these results suggest that an early viral gene is responsible. Degradation of PKR is a rare mechanism to oppose PKR activity, and it has been described in only six RNA viruses. To our knowledge, this is the first example of a DNA virus counteracting PKR by degrading it.",2019 Apr 23,"['Goodman, Danielle E.', 'Pretto, Carla D.', 'Krepostman, Tomas A.', 'Carnahan, Kelly E.', 'Spindler, Katherine R.']",mBio,,,False
cbfcaf5b2c498036a3f6714d8223aa3a3fb5d2cf,PMC,Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR),http://dx.doi.org/10.1128/mBio.00668-19,PMC6479006,31015330,CC BY,"Protein kinase R (PKR) plays a major role in activating host immunity during infection by sensing double-stranded RNA (dsRNA) produced by viruses. Once activated by dsRNA, PKR phosphorylates the translation factor eukaryotic initiation factor 2α (eIF2α), halting cellular translation. Many viruses have methods of inhibiting PKR activation or its downstream effects, circumventing protein synthesis shutdown. These include sequestering dsRNA or producing proteins that bind to and inhibit PKR activation. Here we describe our finding that in multiple cell types, PKR was depleted during mouse adenovirus type 1 (MAV-1) infection. MAV-1 did not appear to be targeting PKR at the transcriptional or translational level, because total PKR mRNA levels and levels of PKR mRNA bound to polysomes were unchanged or increased during MAV-1 infection. However, inhibiting the proteasome reduced the PKR depletion seen in MAV-1-infected cells, whereas inhibiting the lysosome had no effect. This suggests that proteasomal degradation alone is responsible for PKR degradation during MAV-1 infection. Time course experiments indicated that the degradation occurs early after infection. Infecting cells with UV-inactivated virus prevented PKR degradation, whereas inhibiting viral DNA replication did not. Together, these results suggest that an early viral gene is responsible. Degradation of PKR is a rare mechanism to oppose PKR activity, and it has been described in only six RNA viruses. To our knowledge, this is the first example of a DNA virus counteracting PKR by degrading it.",2019 Apr 23,"['Goodman, Danielle E.', 'Pretto, Carla D.', 'Krepostman, Tomas A.', 'Carnahan, Kelly E.', 'Spindler, Katherine R.']",mBio,,,False
935dcce8533a33256fd175c373620cfc42705329,PMC,Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR),http://dx.doi.org/10.1128/mBio.00668-19,PMC6479006,31015330,CC BY,"Protein kinase R (PKR) plays a major role in activating host immunity during infection by sensing double-stranded RNA (dsRNA) produced by viruses. Once activated by dsRNA, PKR phosphorylates the translation factor eukaryotic initiation factor 2α (eIF2α), halting cellular translation. Many viruses have methods of inhibiting PKR activation or its downstream effects, circumventing protein synthesis shutdown. These include sequestering dsRNA or producing proteins that bind to and inhibit PKR activation. Here we describe our finding that in multiple cell types, PKR was depleted during mouse adenovirus type 1 (MAV-1) infection. MAV-1 did not appear to be targeting PKR at the transcriptional or translational level, because total PKR mRNA levels and levels of PKR mRNA bound to polysomes were unchanged or increased during MAV-1 infection. However, inhibiting the proteasome reduced the PKR depletion seen in MAV-1-infected cells, whereas inhibiting the lysosome had no effect. This suggests that proteasomal degradation alone is responsible for PKR degradation during MAV-1 infection. Time course experiments indicated that the degradation occurs early after infection. Infecting cells with UV-inactivated virus prevented PKR degradation, whereas inhibiting viral DNA replication did not. Together, these results suggest that an early viral gene is responsible. Degradation of PKR is a rare mechanism to oppose PKR activity, and it has been described in only six RNA viruses. To our knowledge, this is the first example of a DNA virus counteracting PKR by degrading it.",2019 Apr 23,"['Goodman, Danielle E.', 'Pretto, Carla D.', 'Krepostman, Tomas A.', 'Carnahan, Kelly E.', 'Spindler, Katherine R.']",mBio,,,False
6f76dc6867171ff5bbcba1ff4c0ebb07c0b06778,PMC,Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR),http://dx.doi.org/10.1128/mBio.00668-19,PMC6479006,31015330,CC BY,"Protein kinase R (PKR) plays a major role in activating host immunity during infection by sensing double-stranded RNA (dsRNA) produced by viruses. Once activated by dsRNA, PKR phosphorylates the translation factor eukaryotic initiation factor 2α (eIF2α), halting cellular translation. Many viruses have methods of inhibiting PKR activation or its downstream effects, circumventing protein synthesis shutdown. These include sequestering dsRNA or producing proteins that bind to and inhibit PKR activation. Here we describe our finding that in multiple cell types, PKR was depleted during mouse adenovirus type 1 (MAV-1) infection. MAV-1 did not appear to be targeting PKR at the transcriptional or translational level, because total PKR mRNA levels and levels of PKR mRNA bound to polysomes were unchanged or increased during MAV-1 infection. However, inhibiting the proteasome reduced the PKR depletion seen in MAV-1-infected cells, whereas inhibiting the lysosome had no effect. This suggests that proteasomal degradation alone is responsible for PKR degradation during MAV-1 infection. Time course experiments indicated that the degradation occurs early after infection. Infecting cells with UV-inactivated virus prevented PKR degradation, whereas inhibiting viral DNA replication did not. Together, these results suggest that an early viral gene is responsible. Degradation of PKR is a rare mechanism to oppose PKR activity, and it has been described in only six RNA viruses. To our knowledge, this is the first example of a DNA virus counteracting PKR by degrading it.",2019 Apr 23,"['Goodman, Danielle E.', 'Pretto, Carla D.', 'Krepostman, Tomas A.', 'Carnahan, Kelly E.', 'Spindler, Katherine R.']",mBio,,,False
2db41d29193e4d65b5a7d29585ed34f8aa85bdd1,PMC,Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR),http://dx.doi.org/10.1128/mBio.00668-19,PMC6479006,31015330,CC BY,"Protein kinase R (PKR) plays a major role in activating host immunity during infection by sensing double-stranded RNA (dsRNA) produced by viruses. Once activated by dsRNA, PKR phosphorylates the translation factor eukaryotic initiation factor 2α (eIF2α), halting cellular translation. Many viruses have methods of inhibiting PKR activation or its downstream effects, circumventing protein synthesis shutdown. These include sequestering dsRNA or producing proteins that bind to and inhibit PKR activation. Here we describe our finding that in multiple cell types, PKR was depleted during mouse adenovirus type 1 (MAV-1) infection. MAV-1 did not appear to be targeting PKR at the transcriptional or translational level, because total PKR mRNA levels and levels of PKR mRNA bound to polysomes were unchanged or increased during MAV-1 infection. However, inhibiting the proteasome reduced the PKR depletion seen in MAV-1-infected cells, whereas inhibiting the lysosome had no effect. This suggests that proteasomal degradation alone is responsible for PKR degradation during MAV-1 infection. Time course experiments indicated that the degradation occurs early after infection. Infecting cells with UV-inactivated virus prevented PKR degradation, whereas inhibiting viral DNA replication did not. Together, these results suggest that an early viral gene is responsible. Degradation of PKR is a rare mechanism to oppose PKR activity, and it has been described in only six RNA viruses. To our knowledge, this is the first example of a DNA virus counteracting PKR by degrading it.",2019 Apr 23,"['Goodman, Danielle E.', 'Pretto, Carla D.', 'Krepostman, Tomas A.', 'Carnahan, Kelly E.', 'Spindler, Katherine R.']",mBio,,,False
95f67467b1dc45910cfadae6a3a5fadfed1b0f8d,PMC,Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR),http://dx.doi.org/10.1128/mBio.00668-19,PMC6479006,31015330,CC BY,"Protein kinase R (PKR) plays a major role in activating host immunity during infection by sensing double-stranded RNA (dsRNA) produced by viruses. Once activated by dsRNA, PKR phosphorylates the translation factor eukaryotic initiation factor 2α (eIF2α), halting cellular translation. Many viruses have methods of inhibiting PKR activation or its downstream effects, circumventing protein synthesis shutdown. These include sequestering dsRNA or producing proteins that bind to and inhibit PKR activation. Here we describe our finding that in multiple cell types, PKR was depleted during mouse adenovirus type 1 (MAV-1) infection. MAV-1 did not appear to be targeting PKR at the transcriptional or translational level, because total PKR mRNA levels and levels of PKR mRNA bound to polysomes were unchanged or increased during MAV-1 infection. However, inhibiting the proteasome reduced the PKR depletion seen in MAV-1-infected cells, whereas inhibiting the lysosome had no effect. This suggests that proteasomal degradation alone is responsible for PKR degradation during MAV-1 infection. Time course experiments indicated that the degradation occurs early after infection. Infecting cells with UV-inactivated virus prevented PKR degradation, whereas inhibiting viral DNA replication did not. Together, these results suggest that an early viral gene is responsible. Degradation of PKR is a rare mechanism to oppose PKR activity, and it has been described in only six RNA viruses. To our knowledge, this is the first example of a DNA virus counteracting PKR by degrading it.",2019 Apr 23,"['Goodman, Danielle E.', 'Pretto, Carla D.', 'Krepostman, Tomas A.', 'Carnahan, Kelly E.', 'Spindler, Katherine R.']",mBio,,,False
ebe4f696d0a60c00e499331da56f8151a5407fc0,PMC,Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR),http://dx.doi.org/10.1128/mBio.00668-19,PMC6479006,31015330,CC BY,"Protein kinase R (PKR) plays a major role in activating host immunity during infection by sensing double-stranded RNA (dsRNA) produced by viruses. Once activated by dsRNA, PKR phosphorylates the translation factor eukaryotic initiation factor 2α (eIF2α), halting cellular translation. Many viruses have methods of inhibiting PKR activation or its downstream effects, circumventing protein synthesis shutdown. These include sequestering dsRNA or producing proteins that bind to and inhibit PKR activation. Here we describe our finding that in multiple cell types, PKR was depleted during mouse adenovirus type 1 (MAV-1) infection. MAV-1 did not appear to be targeting PKR at the transcriptional or translational level, because total PKR mRNA levels and levels of PKR mRNA bound to polysomes were unchanged or increased during MAV-1 infection. However, inhibiting the proteasome reduced the PKR depletion seen in MAV-1-infected cells, whereas inhibiting the lysosome had no effect. This suggests that proteasomal degradation alone is responsible for PKR degradation during MAV-1 infection. Time course experiments indicated that the degradation occurs early after infection. Infecting cells with UV-inactivated virus prevented PKR degradation, whereas inhibiting viral DNA replication did not. Together, these results suggest that an early viral gene is responsible. Degradation of PKR is a rare mechanism to oppose PKR activity, and it has been described in only six RNA viruses. To our knowledge, this is the first example of a DNA virus counteracting PKR by degrading it.",2019 Apr 23,"['Goodman, Danielle E.', 'Pretto, Carla D.', 'Krepostman, Tomas A.', 'Carnahan, Kelly E.', 'Spindler, Katherine R.']",mBio,,,False
1dcadb516b775fc9b1ab7cda8e910f728d13eb77,PMC,Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR),http://dx.doi.org/10.1128/mBio.00668-19,PMC6479006,31015330,CC BY,"Protein kinase R (PKR) plays a major role in activating host immunity during infection by sensing double-stranded RNA (dsRNA) produced by viruses. Once activated by dsRNA, PKR phosphorylates the translation factor eukaryotic initiation factor 2α (eIF2α), halting cellular translation. Many viruses have methods of inhibiting PKR activation or its downstream effects, circumventing protein synthesis shutdown. These include sequestering dsRNA or producing proteins that bind to and inhibit PKR activation. Here we describe our finding that in multiple cell types, PKR was depleted during mouse adenovirus type 1 (MAV-1) infection. MAV-1 did not appear to be targeting PKR at the transcriptional or translational level, because total PKR mRNA levels and levels of PKR mRNA bound to polysomes were unchanged or increased during MAV-1 infection. However, inhibiting the proteasome reduced the PKR depletion seen in MAV-1-infected cells, whereas inhibiting the lysosome had no effect. This suggests that proteasomal degradation alone is responsible for PKR degradation during MAV-1 infection. Time course experiments indicated that the degradation occurs early after infection. Infecting cells with UV-inactivated virus prevented PKR degradation, whereas inhibiting viral DNA replication did not. Together, these results suggest that an early viral gene is responsible. Degradation of PKR is a rare mechanism to oppose PKR activity, and it has been described in only six RNA viruses. To our knowledge, this is the first example of a DNA virus counteracting PKR by degrading it.",2019 Apr 23,"['Goodman, Danielle E.', 'Pretto, Carla D.', 'Krepostman, Tomas A.', 'Carnahan, Kelly E.', 'Spindler, Katherine R.']",mBio,,,False
e8dcb73fafb728fc6297e33e0374b7ef8016e1ef,PMC,Active Immunoprophylaxis and Vaccine Augmentations Mediated by a Novel Plasmid DNA Formulation,http://dx.doi.org/10.1089/hum.2018.241,PMC6479233,30860399,CC BY,"Plasmid DNA (pDNA) gene delivery is a highly versatile technology that has the potential to address a multitude of unmet medical needs. Advances in pDNA delivery to host tissue with the employment of in vivo electroporation (EP) have led to significantly enhanced gene expression and the recent demonstration of clinical efficacy with the platform. Building upon this platform, this study reports that enzyme-mediated modification of the muscle tissue extracellular matrix structure at the site of pDNA delivery operates in a synergistic manner with EP to enhance both local and systemic gene expression further. Specifically, administration of chondroitinase ABC (Cho ABC) to the site of intramuscular delivery of pDNA led to transient disruption of chondroitin sulfate scaffolding barrier, permitting enhanced gene distribution and expression across the tissue. The employment of Cho ABC in combination with CELLECTRA(®) intramuscular EP resulted in increased gene expression by 5.5-fold in mice and 17.98-fold in rabbits. The study demonstrates how this protocol can be universally applied to an active prophylaxis platform to increase the in vivo production of functional immunoglobulin G, and to DNA vaccine protocols to permit drug dose sparing. The data indicate the Cho ABC formulation to be of significant value upon combination with EP to drive enhanced gene expression levels in pDNA delivery protocols.",2019 Apr 1,"['Schommer, Nina N.', 'Nguyen, Jacklyn', 'Yung, Bryan S.', 'Schultheis, Katherine', 'Muthumani, Kar', 'Weiner, David B.', 'Humeau, Laurent', 'Broderick, Kate E.', 'Smith, Trevor R.F.']",Hum Gene Ther,,,True
e73fb635f2109543e96f53739fdbc9db8576c17f,PMC,Active Immunoprophylaxis and Vaccine Augmentations Mediated by a Novel Plasmid DNA Formulation,http://dx.doi.org/10.1089/hum.2018.241,PMC6479233,30860399,CC BY,"Plasmid DNA (pDNA) gene delivery is a highly versatile technology that has the potential to address a multitude of unmet medical needs. Advances in pDNA delivery to host tissue with the employment of in vivo electroporation (EP) have led to significantly enhanced gene expression and the recent demonstration of clinical efficacy with the platform. Building upon this platform, this study reports that enzyme-mediated modification of the muscle tissue extracellular matrix structure at the site of pDNA delivery operates in a synergistic manner with EP to enhance both local and systemic gene expression further. Specifically, administration of chondroitinase ABC (Cho ABC) to the site of intramuscular delivery of pDNA led to transient disruption of chondroitin sulfate scaffolding barrier, permitting enhanced gene distribution and expression across the tissue. The employment of Cho ABC in combination with CELLECTRA(®) intramuscular EP resulted in increased gene expression by 5.5-fold in mice and 17.98-fold in rabbits. The study demonstrates how this protocol can be universally applied to an active prophylaxis platform to increase the in vivo production of functional immunoglobulin G, and to DNA vaccine protocols to permit drug dose sparing. The data indicate the Cho ABC formulation to be of significant value upon combination with EP to drive enhanced gene expression levels in pDNA delivery protocols.",2019 Apr 1,"['Schommer, Nina N.', 'Nguyen, Jacklyn', 'Yung, Bryan S.', 'Schultheis, Katherine', 'Muthumani, Kar', 'Weiner, David B.', 'Humeau, Laurent', 'Broderick, Kate E.', 'Smith, Trevor R.F.']",Hum Gene Ther,,,False
92a610f79071097c319a2f766ef488f1956c48f5,PMC,Active Immunoprophylaxis and Vaccine Augmentations Mediated by a Novel Plasmid DNA Formulation,http://dx.doi.org/10.1089/hum.2018.241,PMC6479233,30860399,CC BY,"Plasmid DNA (pDNA) gene delivery is a highly versatile technology that has the potential to address a multitude of unmet medical needs. Advances in pDNA delivery to host tissue with the employment of in vivo electroporation (EP) have led to significantly enhanced gene expression and the recent demonstration of clinical efficacy with the platform. Building upon this platform, this study reports that enzyme-mediated modification of the muscle tissue extracellular matrix structure at the site of pDNA delivery operates in a synergistic manner with EP to enhance both local and systemic gene expression further. Specifically, administration of chondroitinase ABC (Cho ABC) to the site of intramuscular delivery of pDNA led to transient disruption of chondroitin sulfate scaffolding barrier, permitting enhanced gene distribution and expression across the tissue. The employment of Cho ABC in combination with CELLECTRA(®) intramuscular EP resulted in increased gene expression by 5.5-fold in mice and 17.98-fold in rabbits. The study demonstrates how this protocol can be universally applied to an active prophylaxis platform to increase the in vivo production of functional immunoglobulin G, and to DNA vaccine protocols to permit drug dose sparing. The data indicate the Cho ABC formulation to be of significant value upon combination with EP to drive enhanced gene expression levels in pDNA delivery protocols.",2019 Apr 1,"['Schommer, Nina N.', 'Nguyen, Jacklyn', 'Yung, Bryan S.', 'Schultheis, Katherine', 'Muthumani, Kar', 'Weiner, David B.', 'Humeau, Laurent', 'Broderick, Kate E.', 'Smith, Trevor R.F.']",Hum Gene Ther,,,False
f23650ba9f2c40d8cf0e0a5b0b5770e25810c0a0,PMC,Active Immunoprophylaxis and Vaccine Augmentations Mediated by a Novel Plasmid DNA Formulation,http://dx.doi.org/10.1089/hum.2018.241,PMC6479233,30860399,CC BY,"Plasmid DNA (pDNA) gene delivery is a highly versatile technology that has the potential to address a multitude of unmet medical needs. Advances in pDNA delivery to host tissue with the employment of in vivo electroporation (EP) have led to significantly enhanced gene expression and the recent demonstration of clinical efficacy with the platform. Building upon this platform, this study reports that enzyme-mediated modification of the muscle tissue extracellular matrix structure at the site of pDNA delivery operates in a synergistic manner with EP to enhance both local and systemic gene expression further. Specifically, administration of chondroitinase ABC (Cho ABC) to the site of intramuscular delivery of pDNA led to transient disruption of chondroitin sulfate scaffolding barrier, permitting enhanced gene distribution and expression across the tissue. The employment of Cho ABC in combination with CELLECTRA(®) intramuscular EP resulted in increased gene expression by 5.5-fold in mice and 17.98-fold in rabbits. The study demonstrates how this protocol can be universally applied to an active prophylaxis platform to increase the in vivo production of functional immunoglobulin G, and to DNA vaccine protocols to permit drug dose sparing. The data indicate the Cho ABC formulation to be of significant value upon combination with EP to drive enhanced gene expression levels in pDNA delivery protocols.",2019 Apr 1,"['Schommer, Nina N.', 'Nguyen, Jacklyn', 'Yung, Bryan S.', 'Schultheis, Katherine', 'Muthumani, Kar', 'Weiner, David B.', 'Humeau, Laurent', 'Broderick, Kate E.', 'Smith, Trevor R.F.']",Hum Gene Ther,,,False
5f1e08abe8648487cc1738dac17cb2adb25cffe7,PMC,Cellular Cullin RING Ubiquitin Ligases: Druggable Host Dependency Factors of Cytomegaloviruses,http://dx.doi.org/10.3390/ijms20071636,PMC6479302,30986950,CC BY,"Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that frequently causes morbidity and mortality in individuals with insufficient immunity, such as transplant recipients, AIDS patients, and congenitally infected newborns. Several antiviral drugs are approved to treat HCMV infections. However, resistant HCMV mutants can arise in patients receiving long-term therapy. Additionally, side effects and the risk to cause birth defects limit the use of currently approved antivirals against HCMV. Therefore, the identification of new drug targets is of clinical relevance. Recent work identified DNA-damage binding protein 1 (DDB1) and the family of the cellular cullin (Cul) RING ubiquitin (Ub) ligases (CRLs) as host-derived factors that are relevant for the replication of human and mouse cytomegaloviruses. The first-in-class CRL inhibitory compound Pevonedistat (also called MLN4924) is currently under investigation as an anti-tumor drug in several clinical trials. Cytomegaloviruses exploit CRLs to regulate the abundance of viral proteins, and to induce the proteasomal degradation of host restriction factors involved in innate and intrinsic immunity. Accordingly, pharmacological blockade of CRL activity diminishes viral replication in cell culture. In this review, we summarize the current knowledge concerning the relevance of DDB1 and CRLs during cytomegalovirus replication and discuss chances and drawbacks of CRL inhibitory drugs as potential antiviral treatment against HCMV.",2019 Apr 2,"['Becker, Tanja', 'Le-Trilling, Vu Thuy Khanh', 'Trilling, Mirko']",Int J Mol Sci,,,True
b08591a37f6db5d579f4e875e8326ae408a257bd,PMC,Glial Cell Expression of PD-L1,http://dx.doi.org/10.3390/ijms20071677,PMC6479336,30987269,CC BY,"The programmed death (PD)-1/PD-L1 pathway is a well-recognized negative immune checkpoint that results in functional inhibition of T-cells. Microglia, the brain-resident immune cells are vital for pathogen detection and initiation of neuroimmune responses. Moreover, microglial cells and astrocytes govern the activity of brain-infiltrating antiviral T-cells through upregulation of PD-L1 expression. While T-cell suppressive responses within brain are undoubtedly beneficial to the host, preventing cytotoxic damage to this vital organ, establishment of a prolonged anti-inflammatory milieu may simultaneously lead to deficiencies in viral clearance. An immune checkpoint blockade targeting the PD-1: PD-L1 (B7-H1; CD274) axis has revolutionized contemporary treatment for a variety of cancers. However, the therapeutic potential of PD1: PD-L1 blockade therapies targeting viral brain reservoirs remains to be determined. For these reasons, it is key to understand both the detrimental and protective functions of this signaling pathway within the brain. This review highlights how glial cells use PD-L1 expression to modulate T-cell effector function and limit detrimental bystander damage, while still retaining an effective defense of the brain.",2019 Apr 4,"['Chauhan, Priyanka', 'Lokensgard, James R.']",Int J Mol Sci,,,True
4d94a96a67f554bab5caafc4501fb7fda538609f,PMC,"Anti-Herpetic, Anti-Dengue and Antineoplastic Activities of Simple and Heterocycle-Fused Derivatives of Terpenyl-1,4-Naphthoquinone and 1,4-Anthraquinone †",http://dx.doi.org/10.3390/molecules24071279,PMC6479402,30986933,CC BY,"Quinones are secondary metabolites of higher plants associated with many biological activities, including antiviral effects and cytotoxicity. In this study, the anti-herpetic and anti-dengue evaluation of 27 terpenyl-1,4-naphthoquinone (NQ), 1,4-anthraquinone (AQ) and heterocycle-fused quinone (HetQ) derivatives was done in vitro against Human Herpesvirus (HHV) type 1 and 2, and Dengue virus serotype 2 (DENV-2). The cytotoxicity on HeLa and Jurkat tumor cell lines was also tested. Using plaque forming unit assays, cell viability assays and molecular docking, we found that NQ 4 was the best antiviral compound, while AQ 11 was the most active and selective molecule on the tested tumor cells. NQ 4 showed a fair antiviral activity against Herpesviruses (EC(50): <0.4 µg/mL, <1.28 µM) and DENV-2 (1.6 µg/mL, 5.1 µM) on pre-infective stages. Additionally, NQ 4 disrupted the viral attachment of HHV-1 to Vero cells (EC(50): 0.12 µg/mL, 0.38 µM) with a very high selectivity index (SI = 1728). The in silico analysis predicted that this quinone could bind to the prefusion form of the E glycoprotein of DENV-2. These findings demonstrate that NQ 4 is a potent and highly selective antiviral compound, while suggesting its ability to prevent Herpes and Dengue infections. Additionally, AQ 11 can be considered of interest as a leader for the design of new anticancer agents.",2019 Apr 2,"['Roa-Linares, Vicky C.', 'Miranda-Brand, Yaneth', 'Tangarife-Castaño, Verónica', 'Ochoa, Rodrigo', 'García, Pablo A.', 'Castro, Mª Ángeles', 'Betancur-Galvis, Liliana', 'San Feliciano, Arturo']",Molecules,,,True
a5f3efe99c8dbe988fef58595e7d6d502109a190,PMC,Public Perception on Healthcare Services: Evidence from Social Media Platforms in China,http://dx.doi.org/10.3390/ijerph16071273,PMC6479867,30974729,CC BY,"Social media has been used as data resource in a growing number of health-related research. The objectives of this study were to identify content volume and sentiment polarity of social media records relevant to healthcare services in China. A list of the key words of healthcare services were used to extract data from WeChat and Qzone, between June 2017 and September 2017. The data were put into a corpus, where content analyses were performed using Tencent natural language processing (NLP). The final corpus contained approximately 29 million records. Records on patient safety were the most frequently mentioned topic (approximately 8.73 million, 30.1% of the corpus), with the contents on humanistic care having received the least social media references (0.43 Million, 1.5%). Sentiment analyses showed 36.1%, 16.4%, and 47.4% of positive, neutral, and negative emotions, respectively. The doctor-patient relationship category had the highest proportion of negative contents (74.9%), followed by service efficiency (59.5%), and nursing service (53.0%). Neutral disposition was found to be the highest (30.4%) in the contents on appointment-booking services. This study added evidence to the magnitude and direction of public perceptions on healthcare services in China’s hospital and pointed to the possibility of monitoring healthcare service improvement, using readily available data in social media.",2019 Apr 10,"['Hu, Guangyu', 'Han, Xueyan', 'Zhou, Huixuan', 'Liu, Yuanli']",Int J Environ Res Public Health,,,True
bb50d0e4b5421258548d38c4dd724d578c013df4,PMC,Public Perception on Healthcare Services: Evidence from Social Media Platforms in China,http://dx.doi.org/10.3390/ijerph16071273,PMC6479867,30974729,CC BY,"Social media has been used as data resource in a growing number of health-related research. The objectives of this study were to identify content volume and sentiment polarity of social media records relevant to healthcare services in China. A list of the key words of healthcare services were used to extract data from WeChat and Qzone, between June 2017 and September 2017. The data were put into a corpus, where content analyses were performed using Tencent natural language processing (NLP). The final corpus contained approximately 29 million records. Records on patient safety were the most frequently mentioned topic (approximately 8.73 million, 30.1% of the corpus), with the contents on humanistic care having received the least social media references (0.43 Million, 1.5%). Sentiment analyses showed 36.1%, 16.4%, and 47.4% of positive, neutral, and negative emotions, respectively. The doctor-patient relationship category had the highest proportion of negative contents (74.9%), followed by service efficiency (59.5%), and nursing service (53.0%). Neutral disposition was found to be the highest (30.4%) in the contents on appointment-booking services. This study added evidence to the magnitude and direction of public perceptions on healthcare services in China’s hospital and pointed to the possibility of monitoring healthcare service improvement, using readily available data in social media.",2019 Apr 10,"['Hu, Guangyu', 'Han, Xueyan', 'Zhou, Huixuan', 'Liu, Yuanli']",Int J Environ Res Public Health,,,False
1d75590848a42f84359d8ff9631fdc3145efd631,PMC,The Eukaryotic Translation Initiation Factor 4F Complex Restricts Rotavirus Infection via Regulating the Expression of IRF1 and IRF7,http://dx.doi.org/10.3390/ijms20071580,PMC6480131,30934842,CC BY,"The eIF4F complex is a translation initiation factor that closely regulates translation in response to a multitude of environmental conditions including viral infection. How translation initiation factors regulate rotavirus infection remains poorly understood. In this study, the knockdown of the components of the eIF4F complex using shRNA and CRISPR/Cas9 were performed, respectively. We have demonstrated that loss-of-function of the three components of eIF4F, including eIF4A, eIF4E and eIF4G, remarkably promotes the levels of rotavirus genomic RNA and viral protein VP4. Consistently, knockdown of the negative regulator of eIF4F and programmed cell death protein 4 (PDCD4) inhibits the expression of viral mRNA and the VP4 protein. Mechanically, we confirmed that the silence of the eIF4F complex suppressed the protein level of IRF1 and IRF7 that exert potent antiviral effects against rotavirus infection. Thus, these results demonstrate that the eIF4F complex is an essential host factor restricting rotavirus replication, revealing new targets for the development of new antiviral strategies against rotavirus infection.",2019 Mar 29,"['Chen, Sunrui', 'Feng, Cui', 'Fang, Yan', 'Zhou, Xinying', 'Xu, Lei', 'Wang, Wenshi', 'Kong, Xiangdong', 'P. Peppelenbosch, Maikel', 'Pan, Qiuwei', 'Yin, Yuebang']",Int J Mol Sci,,,True
1068a2a6e9563bf672373a1a06337dbabbe73050,PMC,The Eukaryotic Translation Initiation Factor 4F Complex Restricts Rotavirus Infection via Regulating the Expression of IRF1 and IRF7,http://dx.doi.org/10.3390/ijms20071580,PMC6480131,30934842,CC BY,"The eIF4F complex is a translation initiation factor that closely regulates translation in response to a multitude of environmental conditions including viral infection. How translation initiation factors regulate rotavirus infection remains poorly understood. In this study, the knockdown of the components of the eIF4F complex using shRNA and CRISPR/Cas9 were performed, respectively. We have demonstrated that loss-of-function of the three components of eIF4F, including eIF4A, eIF4E and eIF4G, remarkably promotes the levels of rotavirus genomic RNA and viral protein VP4. Consistently, knockdown of the negative regulator of eIF4F and programmed cell death protein 4 (PDCD4) inhibits the expression of viral mRNA and the VP4 protein. Mechanically, we confirmed that the silence of the eIF4F complex suppressed the protein level of IRF1 and IRF7 that exert potent antiviral effects against rotavirus infection. Thus, these results demonstrate that the eIF4F complex is an essential host factor restricting rotavirus replication, revealing new targets for the development of new antiviral strategies against rotavirus infection.",2019 Mar 29,"['Chen, Sunrui', 'Feng, Cui', 'Fang, Yan', 'Zhou, Xinying', 'Xu, Lei', 'Wang, Wenshi', 'Kong, Xiangdong', 'P. Peppelenbosch, Maikel', 'Pan, Qiuwei', 'Yin, Yuebang']",Int J Mol Sci,,,False
85657444327cc8301d257fbda39df1a02e9d1d40,PMC,Interferon-Stimulated Genes—Mediators of the Innate Immune Response during Canine Distemper Virus Infection,http://dx.doi.org/10.3390/ijms20071620,PMC6480560,30939763,CC BY,"The demyelinating canine distemper virus (CDV)-leukoencephalitis represents a translational animal model for multiple sclerosis. The present study investigated the expression of type I interferon (IFN-I) pathway members in CDV-induced cerebellar lesions to gain an insight into their role in lesion development. Gene expression of 110 manually selected genes in acute, subacute and chronic lesions was analyzed using pre-existing microarray data. Interferon regulatory factor (IRF) 3, IRF7, signal transducer and activator of transcription (STAT) 1, STAT2, MX protein, protein kinase R (PKR), 2′-5′-oligoadenylate synthetase (OAS) 1 and interferon-stimulated gene (ISG) 15 expression were also evaluated using immunohistochemistry. Cellular origin of STAT1, STAT2, MX and PKR were determined using immunofluorescence. CDV infection caused an increased expression of the antiviral effector proteins MX, PKR, OAS1 and ISG15, which probably contributed to a restricted viral replication, particularly in neurons and oligodendrocytes. This increase might be partly mediated by IRF-dependent pathways due to the lack of changes in IFN-I levels and absence of STAT2 in astrocytes. Nevertheless, activated microglia/macrophages showed a strong expression of STAT1, STAT2 and MX proteins in later stages of the disease, indicating a strong activation of the IFN-I signaling cascade, which might be involved in the aggravation of bystander demyelination.",2019 Apr 1,"['Klotz, Daniela', 'Gerhauser, Ingo']",Int J Mol Sci,,,True
d23b8f0a2ccd3292007e5d31609e6cc42ca3ca77,PMC,Interferon-Stimulated Genes—Mediators of the Innate Immune Response during Canine Distemper Virus Infection,http://dx.doi.org/10.3390/ijms20071620,PMC6480560,30939763,CC BY,"The demyelinating canine distemper virus (CDV)-leukoencephalitis represents a translational animal model for multiple sclerosis. The present study investigated the expression of type I interferon (IFN-I) pathway members in CDV-induced cerebellar lesions to gain an insight into their role in lesion development. Gene expression of 110 manually selected genes in acute, subacute and chronic lesions was analyzed using pre-existing microarray data. Interferon regulatory factor (IRF) 3, IRF7, signal transducer and activator of transcription (STAT) 1, STAT2, MX protein, protein kinase R (PKR), 2′-5′-oligoadenylate synthetase (OAS) 1 and interferon-stimulated gene (ISG) 15 expression were also evaluated using immunohistochemistry. Cellular origin of STAT1, STAT2, MX and PKR were determined using immunofluorescence. CDV infection caused an increased expression of the antiviral effector proteins MX, PKR, OAS1 and ISG15, which probably contributed to a restricted viral replication, particularly in neurons and oligodendrocytes. This increase might be partly mediated by IRF-dependent pathways due to the lack of changes in IFN-I levels and absence of STAT2 in astrocytes. Nevertheless, activated microglia/macrophages showed a strong expression of STAT1, STAT2 and MX proteins in later stages of the disease, indicating a strong activation of the IFN-I signaling cascade, which might be involved in the aggravation of bystander demyelination.",2019 Apr 1,"['Klotz, Daniela', 'Gerhauser, Ingo']",Int J Mol Sci,,,False
5bb8f28608aad3bde8b470c81025ce3c9e3a5fc3,PMC,Impacts of Road Traffic Network and Socioeconomic Factors on the Diffusion of 2009 Pandemic Influenza A (H1N1) in Mainland China,http://dx.doi.org/10.3390/ijerph16071223,PMC6480969,30959783,CC BY,"The 2009 pandemic influenza virus caused the majority of the influenza A virus infections in China in 2009. It arrived in several Chinese cities from imported cases and then spread as people travelled domestically by all means of transportation, among which road traffic was the most commonly used for daily commuting. Spatial variation in socioeconomic status not only accelerates migration across regions but also partly induces the differences in epidemic processes and in responses to epidemics across regions. However, the roles of both road travel and socioeconomic factors have not received the attention they deserve. Here, we constructed a national highway network for and between 333 cities in mainland China and extracted epidemiological variables and socioeconomic factors for each city. We calculated classic centrality measures for each city in the network and proposed two new measures (SumRatio and Multicenter Distance). We evaluated the correlation between the centrality measures and epidemiological features and conducted a spatial autoregression to quantify the impacts of road network and socioeconomic factors during the outbreak. The results showed that epidemics had more significant relationships with both our new measures than the classic ones. Higher population density, higher per person income, larger SumRatio and Multicenter Distance, more hospitals and college students, and lower per person GDP were associated with higher cumulative incidence. Higher population density and number of slaughtered pigs were found to advance epidemic arrival time. Higher population density, more colleges and slaughtered pigs, and lower Multicenter Distance were associated with longer epidemic duration. In conclusion, road transport and socioeconomic status had significant impacts and should be considered for the prevention and control of future pandemics.",2019 Apr 5,"['Xu, Bo', 'Tian, Huaiyu', 'Sabel, Clive Eric', 'Xu, Bing']",Int J Environ Res Public Health,,,True
498ab135eba6df8af4542ec486dd65493781c2c2,PMC,Polymorphisms in CLDN1 are associated with age and differentiation of triple-negative breast cancer patients,http://dx.doi.org/10.1042/BSR20181952,PMC6481238,30910845,CC BY,"Purpose: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. It is very important to explore novel biomarkers to better clarify the characteristics of TNBC. It has been reported that polymorphisms in claudin 1 (CLDN1) are associated with risk of several cancers. But till now, there is no report about these polymorphisms and TNBC. Patients and methods: Between January 2004 and December 2013, 267 patients with stage I–III primary TNBC were included in our study. We investigated the association between polymorphisms in CLDN1 gene and clinicopathological characteristics or survival of these patients. We used Haploview 4.2 software to identify Tag single nucleotide polymorphisms (SNPs). MassARRAY MALDI-TOF System was used for genotyping. Results: We found that rs10513846 GA genotype was associated with older age [P=0.013, hazard ratios (HR) = 2.231, 95% confidence interval (CI): 1.186–4.195]. Rs10513846 AA genotype carriers were more likely to develop grade 3 tumors (P=0.005, HR = 2.889, 95% CI: 1.389–6.007). And rs9283658 genotypes were also related to grade, more patients with grade 3 tumors were rs9283658 CC genotype carriers (P=0.023, HR = 0.446, 95% CI: 0.222–0.894). There was no association between polymorphisms in CLDN1 and survival of TNBC patients. After multivariate analysis, tumor size (P=0.021, HR = 3.146, 95% CI: 1.185–8.354) and lymph node status (P<0.001, HR = 10.930, 95% CI: 3.276–36.470) were demonstrated to be independent prognostic factors. Conclusion: We first demonstrated that polymorphisms in CLDN1 gene were associated with age and differentiation of TNBC patients.",2019 Apr 23,"['Hu, Aimin', 'Li, Junyu', 'Ruan, Shufang', 'Fan, Ying', 'Liao, Yuqian']",Biosci Rep,,,False
ae36c3fc53af891f884df86ac68bcebd0ad37229,PMC,Polymorphisms in CLDN1 are associated with age and differentiation of triple-negative breast cancer patients,http://dx.doi.org/10.1042/BSR20181952,PMC6481238,30910845,CC BY,"Purpose: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. It is very important to explore novel biomarkers to better clarify the characteristics of TNBC. It has been reported that polymorphisms in claudin 1 (CLDN1) are associated with risk of several cancers. But till now, there is no report about these polymorphisms and TNBC. Patients and methods: Between January 2004 and December 2013, 267 patients with stage I–III primary TNBC were included in our study. We investigated the association between polymorphisms in CLDN1 gene and clinicopathological characteristics or survival of these patients. We used Haploview 4.2 software to identify Tag single nucleotide polymorphisms (SNPs). MassARRAY MALDI-TOF System was used for genotyping. Results: We found that rs10513846 GA genotype was associated with older age [P=0.013, hazard ratios (HR) = 2.231, 95% confidence interval (CI): 1.186–4.195]. Rs10513846 AA genotype carriers were more likely to develop grade 3 tumors (P=0.005, HR = 2.889, 95% CI: 1.389–6.007). And rs9283658 genotypes were also related to grade, more patients with grade 3 tumors were rs9283658 CC genotype carriers (P=0.023, HR = 0.446, 95% CI: 0.222–0.894). There was no association between polymorphisms in CLDN1 and survival of TNBC patients. After multivariate analysis, tumor size (P=0.021, HR = 3.146, 95% CI: 1.185–8.354) and lymph node status (P<0.001, HR = 10.930, 95% CI: 3.276–36.470) were demonstrated to be independent prognostic factors. Conclusion: We first demonstrated that polymorphisms in CLDN1 gene were associated with age and differentiation of TNBC patients.",2019 Apr 23,"['Hu, Aimin', 'Li, Junyu', 'Ruan, Shufang', 'Fan, Ying', 'Liao, Yuqian']",Biosci Rep,,,True
2f74928e0d29d3724e184de8839982d6a44fe8bf,PMC,Understanding Fc Receptor Involvement in Inflammatory Diseases: From Mechanisms to New Therapeutic Tools,http://dx.doi.org/10.3389/fimmu.2019.00811,PMC6481281,31057544,CC BY,"Fc receptors (FcRs) belong to the ITAM-associated receptor family. FcRs control the humoral and innate immunity which are essential for appropriate responses to infections and prevention of chronic inflammation or auto-immune diseases. Following their crosslinking by immune complexes, FcRs play various roles such as modulation of the immune response by released cytokines or of phagocytosis. Here, we review FcR involvement in pathologies leading notably to altered intracellular signaling with functionally relevant consequences to the host, and targeting of Fc receptors as therapeutic approaches. Special emphasis will be given to some FcRs, such as the FcαRI, the FcγRIIA and the FcγRIIIA, which behave like the ancient god Janus depending on the ITAM motif to inhibit or activate immune responses depending on their targeting by monomeric/dimeric immunoglobulins or by immune complexes. This ITAM duality has been recently defined as inhibitory or activating ITAM (ITAMi or ITAMa) which are controlled by Src family kinases. Involvement of various ITAM-bearing FcRs observed during infectious or autoimmune diseases is associated with allelic variants, changes in ligand binding ability responsible for host defense perturbation. During auto-immune diseases such as rheumatoid arthritis, lupus or immune thrombocytopenia, the autoantibodies and immune complexes lead to inflammation through FcR aggregation. We will discuss the role of FcRs in autoimmune diseases, and focus on novel approaches to target FcRs for resolution of antibody-mediated autoimmunity. We will finally also discuss the down-regulation of FcR functionality as a therapeutic approach for autoimmune diseases.",2019 Apr 12,"['Ben Mkaddem, Sanae', 'Benhamou, Marc', 'Monteiro, Renato C.']",Front Immunol,,,True
89a70f5a269900d9e7e4a8b2e325ea1b4adf1bb5,PMC,"Porcine Torovirus (PToV)—A Brief Review of Etiology, Diagnostic Assays and Current Epidemiology",http://dx.doi.org/10.3389/fvets.2019.00120,PMC6482245,31058174,CC BY,"Porcine torovirus (PToV) is a potential enteric swine pathogen, found at especially high rates in piglets with diarrhea. It was first reported in the Netherlands in 1998 and has emerged in many countries around the world. Infections are generally asymptomatic and have not directly caused large economic losses, though co-infections with other swine pathogens and intertype recombination may lead to unpredictable outcomes. This review introduces progress in PToV research regarding its discovery, relationship with other Toroviruses, virion morphological characteristics, genetic structure and variation, recent epidemiology, diagnostic methods, and possibilities for future research.",2019 Apr 18,"['Hu, Zhang-Min', 'Yang, Yong-Le', 'Xu, Ling-Dong', 'Wang, Bin', 'Qin, Pan', 'Huang, Yao-Wei']",Front Vet Sci,,,True
cae0b002b145d21b55c8fdde52e28b269aa405f7,PMC,Development and evaluation of a one-step multiplex real-time TaqMan(®) RT-qPCR assay for the detection and genotyping of equine G3 and G14 rotaviruses in fecal samples,http://dx.doi.org/10.1186/s12985-019-1149-1,PMC6482509,31023319,CC BY,"BACKGROUND: Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and has a negative impact on equine breeding enterprises worldwide. Among ERVA strains infecting foals, the genotypes G3P[12] and G14P[12] are the most prevalent, while infections by strains with other genomic arrangements are infrequent. The identification of circulating strains of ERVA is critical for diagnostic and surveillance purposes, as well as to understand their molecular epidemiology. Current genotyping methods available for ERVA and rotaviruses affecting other animal species rely on Sanger sequencing and are significantly time-consuming, costly and labor intensive. Here, we developed the first one-step multiplex TaqMan(®) real-time reverse transcription polymerase chain reaction (RT-qPCR) assay targeting the NSP3 and VP7 genes of ERVA G3 and G14 genotypes for the rapid detection and G-typing directly from fecal specimens. METHODS: A one-step multiplex TaqMan(®) RT-qPCR assay targeting the NSP3 and VP7 genes of ERVA G3 and G14 genotypes was designed. The analytical sensitivity was assessed using serial dilutions of in vitro transcribed RNA containing the target sequences while the analytical specificity was determined using RNA and DNA derived from a panel of group A rotaviruses along with other equine viruses and bacteria. The clinical performance of this multiplex assay was evaluated using a panel of 177 fecal samples and compared to a VP7-specific standard RT-PCR assay and Sanger sequencing. Limits of detection (LOD), sensitivity, specificity, and agreement were determined. RESULTS: The multiplex G3 and G14 VP7 assays demonstrated high specificity and efficiency, with perfect linearity. A 100-fold difference in their analytical sensitivity was observed when compared to the singleplex assays; however, this difference did not have an impact on the clinical performance. Clinical performance of the multiplex RT-qPCR assay demonstrated that this assay had a high sensitivity/specificity for every target (100% for NSP3, > 90% for G3 VP7 and > 99% for G14 VP7, respectively) and high overall agreement (> 98%) compared to conventional RT-PCR and sequencing. CONCLUSIONS: This new multiplex RT-qPCR assay constitutes a useful, very reliable tool that could significantly aid in the rapid detection and G-typing of ERVA strains circulating in the field.",2019 Apr 25,"['Carossino, Mariano', 'Barrandeguy, Maria E.', 'Erol, Erdal', 'Li, Yanqiu', 'Balasuriya, Udeni B. R.']",Virol J,,,True
8d0b98bb0c601d8a636e49bad7d2449b7dce32ff,PMC,"The Role of Interleukin-1 cytokine family (IL-1β, IL-37) and interleukin-12 cytokine family (IL-12, IL-35) in eumycetoma infection pathogenesis",http://dx.doi.org/10.1371/journal.pntd.0007098,PMC6483278,30946748,CC BY,"Mycetoma is a neglected tropical disease, endemic in many tropical and subtropical regions, characterised by massive deformity and disability and can be fatal if untreated early and appropriately. Interleukins (IL) -35 and IL-37 are newly discovered cytokines that play an important role in suppressing the immune system. However, the expression of these interleukins in patients with Madurella mycetomatis (M. mycetomatis) induced eumycetoma has not yet been explored. The aim of this study is to determine the levels of IL-1 family (IL-1β, IL-37) and IL-12 family (IL-12, IL-35) in a group of these patients and the association between these cytokines levels and the patients’ demographic characteristics. The present, case-control study was conducted at the Mycetoma Research Centre, Soba University Hospital, University of Khartoum, Sudan and it included 140 individuals. They were divided into two groups; group I: healthy controls [n = 70; median age 25 years (range 12 to 70 years)]. Group II: mycetoma patients [n = 70 patients; median age 25 (range 13 to 70 years)]. Cytokines levels were measured in sera using enzyme linked immunosorbent assay (ELISA). There was a significant negative correlation between IL-1β and IL-12 levels and lesion size and disease duration, while IL-37 and IL-35 levels were significantly positively correlated with both lesion size and disease duration. The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a negative significant association with IL-1β cytokine, where a unit increment in IL-1β will decrease the levels of IL-37 by 35.28 pg/ml. The levels of IL-37 among the patients with a duration of mycetoma infection ≤ 1 year were significantly low by an average of 18.45 pg/ml compared to patients with a mycetoma infection’s duration of ≥ 5years (reference group). Furthermore, the risk factors of higher levels of IL-35 in mycetoma patients revealed a negative significant association with IL-12, as a unit increment in IL-12 decreases the levels of IL-35 by 8.99 pg/ml (p < 0.001). Levels of IL-35 among the patients with duration of mycetoma infection ≤ one year were significantly low on average by 41.82 pg/ml (p value = 0.002) compared to patients with a duration of mycetoma infection ≥ 5 years (reference group). In conclusion, this study indicates that both IL-35 and IL-37 are negatively associated with the levels of IL-1β and IL-12 in eumycetoma mycetoma infection; and high levels of IL-37 and IL-35 may have a negative impact on disease progression.",2019 Apr 4,"['Abushouk, Amir', 'Nasr, Amre', 'Masuadi, Emad', 'Allam, Gamal', 'Siddig, Emmanuel E.', 'Fahal, Ahmed H.']",PLoS Negl Trop Dis,,,True
cb98e2840f97f1b0425ac66e90784b5fe5fcecb7,PMC,Canine infectious respiratory disease: New insights into the etiology and epidemiology of associated pathogens,http://dx.doi.org/10.1371/journal.pone.0215817,PMC6483346,31022218,CC BY,"Canine infectious respiratory disease (CIRD) is a syndrome where multiple viral and bacterial pathogens are involved sequentially or synergistically to cause illness. There is limited information regarding the prevalence of pathogens related to CIRD in the United States as well as the role of co-infections in the pathogenesis of the syndrome. We aimed to conduct a comprehensive etiologic and epidemiologic study of multiple CIRD agents in a diverse dog population using molecular methods and statistical modeling analyses. In addition, a novel probe-based multiplex real-time PCR was developed to simultaneously detect and differentiate two species of Mycoplasma (M. canis and M. cynos). Canine adenovirus, canine distemper virus, canine parainfluenza virus, coronavirus, influenza A virus (H3N2 and H3N8), Bordetella bronchiseptica, M. canis, M. cynos and Streptococcus equi subsp. zooepidemicus were investigated in specimens from clinically ill and asymptomatic dogs received at the Athens Veterinary Diagnostic Laboratory. Results showed low occurrence of classical CIRD agents such as B. bronchiseptica, canine adenovirus and distemper virus, while highlighting the potential role of emerging bacteria such as M. canis and M. cynos. Statistical modeling analyses of CIRD pathogens emphasized the impact of co-infections on the severity of clinical presentation, and showed that host factors, such as animal age, are the most important predictors of disease severity. This study provides new insights into the current understanding of the prevalence and role of co-infections with selected viruses and bacteria in the etiology of CIRD, while underscoring the importance of molecular diagnosis and vaccination against this disease.",2019 Apr 25,"['Maboni, Grazieli', 'Seguel, Mauricio', 'Lorton, Ana', 'Berghaus, Roy', 'Sanchez, Susan']",PLoS One,,,True
f9d015b725d247948462394085053cff02c94791,PMC,FOXO1-regulated lncRNA LINC01197 inhibits pancreatic adenocarcinoma cell proliferation by restraining Wnt/β-catenin signaling,http://dx.doi.org/10.1186/s13046-019-1174-3,PMC6485178,31027497,CC BY,"BACKGROUND: Recent studies have revealed that numerous oncogenic long non-coding RNAs (lncRNAs) play pivotal roles in pancreatic ductal adenocarcinoma (PDAC) progression, but little is known about tumor-suppressive lncRNAs in PDAC. This study was conducted to evaluate the function of tumor-suppressive LINC01197 in PDAC progression and investigate the detailed mechanisms. METHODS: LncRNA microarray was used to identify differentially expressed lncRNAs in FOXO1-overexpressing PANC1 cells. LINC01197 expression was evaluated by quantitative PCR, Northern blotting, and fluorescence in situ hybridization. The Cancer Genome Atlas database was used to analyze the prognostic role of LNC01197 in PDAC. A luciferase reporter assay was performed to confirm the interaction between LNC01197 and FOXO1. The biological function of LINC01197 was evaluated by colony formation assay in vitro and in an animal subcutaneous tumorigenesis experiment and Ki67 staining in vivo. RNA-pulldown, western blotting, RNA immunoprecipitation assay, and co-immunoprecipitation were further performed to determine the molecular mechanism of LNC01197 and β-catenin in the Wnt pathway. RESULTS: We found that a FOXO1-related lncRNA, LINC01197, was significantly decreased in PDAC malignant tissues and that its low expression predicted poor prognosis. Moreover, LINC01197 was mainly localized in the nucleus and inhibited PDAC cell proliferation both in vitro and in vivo. Mechanistically, LINC01197 was found to bind to β-catenin and inhibit Wnt/β-catenin signaling activity by disrupting β-catenin binding to TCF4 in PDAC cells. CONCLUSIONS: The novel FOXO1/LINC01197/β-catenin axis was dysregulated during PDAC progression. Our study provides insight into the mechanisms of LINC01197 in PDAC and reveal a potential target for PDAC clinical therapy and prognostic prediction.",2019 Apr 26,"['Ling, Jing', 'Wang, Fan', 'Liu, Chuan', 'Dong, Xiao', 'Xue, Ying', 'Jia, Xuebing', 'Song, Weifeng', 'Li, Qi']",J Exp Clin Cancer Res,,,True
b4d5ebb1c574e7ecf75864238a2bedcac860b5bb,PMC,Molecular epidemiology of canine parvovirus type 2 in Vietnam from November 2016 to February 2018,http://dx.doi.org/10.1186/s12985-019-1159-z,PMC6486976,31029137,CC BY,"BACKGROUND: Canine parvovirus type 2 (CPV-2) was first identified in the late 1970s; it causes intestinal hemorrhage with severe bloody diarrhea in kennels and dog shelters worldwide. Since its emergence, CPV-2 has been replaced with new genetic variants (CPV-2a, CPV-2b, and CPV-2c). Currently, information about the genotype prevalence of CPV-2 in Vietnam is limited. In the present study, we investigated the genotype prevalence and distribution of CPV-2 in the three regions of Vietnam. METHODS: Rectal swabs were collected from 260 dogs with suspected CPV-2 infection from northern, central, and southern Vietnam from November 2016 to February 2018. All samples were identified as parvovirus positive by real-time PCR, and further genotyping was performed using a SimpleProbe® real-time PCR assay. RESULTS: Of the 260 Vietnamese CPV-2 isolates, 6 isolates (2.31%) were identified as CPV-2a, 251 isolates (96.54%) were identified as CPV-2c and 3 isolates (1.15%) were untypable using the SimpleProbe® real-time PCR assay. In northern Vietnam, the percentages of CPV-2a and CPV-2c were 2.97% (3/101) and 97.3% (98/101), respectively. In central Vietnam, the percentages of CPV-2a and CPV-2c were 1.11% (1/90) and 98.89% (89/90), respectively. In southern Vietnam, the percentages of CPV-2a and CPV-2c were 3.03% (2/66) and 96.97% (64/66), respectively. CPV-2b was not observed in this study. The VP2 genes of CPV-2c in Vietnam are more genetically similar to those of CPV-2c strains in China and Taiwan than to those of prototype CPV-2c strains (FJ222821) or the first Vietnamese CPV-2c (AB120727). CONCLUSION: The present study provides evidence that CPV-2c is the most prevalent variant in Vietnam. Phylogenetic analysis demonstrated that the recent Vietnamese CPV-2c isolates share a common evolutionary origin with Asian CPV-2c strains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-019-1159-z) contains supplementary material, which is available to authorized users.",2019 Apr 27,"['Hoang, Minh', 'Lin, Wei-Hao', 'Le, Van Phan', 'Nga, Bui Thi To', 'Chiou, Ming-Tang', 'Lin, Chao-Nan']",Virol J,,,True
c48bb15af3fe47ce755d022245d64cc0df2537e2,PMC,UBXN1 interacts with the S1 protein of transmissible gastroenteritis coronavirus and plays a role in viral replication,http://dx.doi.org/10.1186/s13567-019-0648-9,PMC6487014,31029162,CC BY,"Transmissible gastroenteritis coronavirus (TGEV) is an enteropathogenic coronavirus that causes diarrhea in pigs and is associated with high morbidity and mortality in sucking piglets. S1 is one of two protein domains in the spike (S) glycoprotein and is responsible for enteric tropism, sialic acid recognition, and host receptor binding. Although there has been extensive research on the S1 protein of TGEV, little is known about the intracellular role of TGEV-S1. In the present study, we used yeast two-hybrid screening of a cDNA library from porcine intestinal cells to identify proteins that interact with TGEV-S1. Among 120 positive clones from the library, 12 intracellular proteins were identified after sequencing and a BLAST search. These intracellular proteins are involved in protein synthesis and degradation, biological signal transduction, and negative control of signaling pathways. Using a glutathione-S-transferase (GST) pulldown assay and Co-IP, we found that UBXN1 interacts with the S1 protein. Here, we observed that TGEV infection led to increased UBXN1 expression levels during the late phase of infection in IPEC-J2 cells. Inhibition of UBXN1 in IPEC-J2 cells via siRNA interference significantly decreased the viral titer and downregulated the expression of S1. UBXN1 overexpression significantly increased the viral copy number. Additionally, we provided data suggesting that UBXN1 negatively regulates IFN-β expression after TGEV infection. Finally, our research indicated that UBXN1 plays a vital role in the process of TGEV infection, making it a candidate target for the development of a novel antiviral method.",2019 Apr 27,"['Yuan, Peng', 'Huang, Shilei', 'Yang, Zhou', 'Xie, Luyi', 'Wang, Kai', 'Yang, Yang', 'Ran, Lin', 'Yu, Qiuhan', 'Song, Zhenhui']",Vet Res,,,True
5187f0f3f45b0a1882a44001d193a24c97b0bb1b,PMC,Current epidemiological status of Middle East respiratory syndrome coronavirus in the world from 1.1.2017 to 17.1.2018: a cross-sectional study,http://dx.doi.org/10.1186/s12879-019-3987-2,PMC6487021,31029095,CC BY,"BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is considered to be responsible for a new viral epidemic and an emergent threat to global health security. This study describes the current epidemiological status of MERS-CoV in the world. METHODS: Epidemiological analysis was performed on data derived from all MERS-CoV cases recorded in the disease outbreak news on WHO website between 1.1.2017 and 17.1.2018. Demographic and clinical information as well as potential contacts and probable risk factors for mortality were extracted based on laboratory-confirmed MERS-CoV cases. RESULTS: A total of 229 MERS-CoV cases, including 70 deaths (30.5%), were recorded in the disease outbreak news on world health organization website over the study period. Based on available details in this study, the case fatality rate in both genders was 30.5% (70/229) [32.1% (55/171) for males and 25.8% (15/58) for females]. The disease occurrence was higher among men [171 cases (74.7%)] than women [58 cases (25.3%)]. Variables such as comorbidities and exposure to MERS-CoV cases were significantly associated with mortality in people affected with MERS-CoV infections, and adjusted odds ratio estimates were 2.2 (95% CI: 1.16, 7.03) and 2.3 (95% CI: 1.35, 8.20), respectively. All age groups had an equal chance of mortality. CONCLUSIONS: In today’s “global village”, there is probability of MERS-CoV epidemic at any time and in any place without prior notice. Thus, health systems in all countries should implement better triage systems for potentially imported cases of MERS-CoV to prevent large epidemics.",2019 Apr 27,"['Mobaraki, Kazhal', 'Ahmadzadeh, Jamal']",BMC Infect Dis,,,True
53c7a39b62fed65316c0e8940334045883a46fb2,PMC,Innate Immune and Inflammatory Responses to Respiratory Viruses,http://dx.doi.org/10.1155/2019/3146065,PMC6487094,31097919,CC BY,,2019 Apr 14,"['Li, Shitao', 'Fu, Bishi', 'Meshram, Chetan D.']",Mediators Inflamm,,,False
a376dd031cbf3924fc3e55c1ed5f2c08fd4c1f82,PMC,Long-read viral metagenomics captures abundant and microdiverse viral populations and their niche-defining genomic islands,http://dx.doi.org/10.7717/peerj.6800,PMC6487183,31086738,CC BY,"Marine viruses impact global biogeochemical cycles via their influence on host community structure and function, yet our understanding of viral ecology is constrained by limitations in host culturing and a lack of reference genomes and ‘universal’ gene markers to facilitate community surveys. Short-read viral metagenomic studies have provided clues to viral function and first estimates of global viral gene abundance and distribution, but their assemblies are confounded by populations with high levels of strain evenness and nucleotide diversity (microdiversity), limiting assembly of some of the most abundant viruses on Earth. Such features also challenge assembly across genomic islands containing niche-defining genes that drive ecological speciation. These populations and features may be successfully captured by single-virus genomics and fosmid-based approaches, at least in abundant taxa, but at considerable cost and technical expertise. Here we established a low-cost, low-input, high throughput alternative sequencing and informatics workflow to improve viral metagenomic assemblies using short-read and long-read technology. The ‘VirION’ (Viral, long-read metagenomics via MinION sequencing) approach was first validated using mock communities where it was found to be as relatively quantitative as short-read methods and provided significant improvements in recovery of viral genomes. We then then applied VirION to the first metagenome from a natural viral community from the Western English Channel. In comparison to a short-read only approach, VirION: (i) increased number and completeness of assembled viral genomes; (ii) captured abundant, highly microdiverse virus populations, and (iii) captured more and longer genomic islands. Together, these findings suggest that VirION provides a high throughput and cost-effective alternative to fosmid and single-virus genomic approaches to more comprehensively explore viral communities in nature.",2019 Apr 25,"['Warwick-Dugdale, Joanna', 'Solonenko, Natalie', 'Moore, Karen', 'Chittick, Lauren', 'Gregory, Ann C.', 'Allen, Michael J.', 'Sullivan, Matthew B.', 'Temperton, Ben']",PeerJ,,,False
b386f0bbf59b80952e0320feacb36572c6c3b9ff,PMC,Long-read viral metagenomics captures abundant and microdiverse viral populations and their niche-defining genomic islands,http://dx.doi.org/10.7717/peerj.6800,PMC6487183,31086738,CC BY,"Marine viruses impact global biogeochemical cycles via their influence on host community structure and function, yet our understanding of viral ecology is constrained by limitations in host culturing and a lack of reference genomes and ‘universal’ gene markers to facilitate community surveys. Short-read viral metagenomic studies have provided clues to viral function and first estimates of global viral gene abundance and distribution, but their assemblies are confounded by populations with high levels of strain evenness and nucleotide diversity (microdiversity), limiting assembly of some of the most abundant viruses on Earth. Such features also challenge assembly across genomic islands containing niche-defining genes that drive ecological speciation. These populations and features may be successfully captured by single-virus genomics and fosmid-based approaches, at least in abundant taxa, but at considerable cost and technical expertise. Here we established a low-cost, low-input, high throughput alternative sequencing and informatics workflow to improve viral metagenomic assemblies using short-read and long-read technology. The ‘VirION’ (Viral, long-read metagenomics via MinION sequencing) approach was first validated using mock communities where it was found to be as relatively quantitative as short-read methods and provided significant improvements in recovery of viral genomes. We then then applied VirION to the first metagenome from a natural viral community from the Western English Channel. In comparison to a short-read only approach, VirION: (i) increased number and completeness of assembled viral genomes; (ii) captured abundant, highly microdiverse virus populations, and (iii) captured more and longer genomic islands. Together, these findings suggest that VirION provides a high throughput and cost-effective alternative to fosmid and single-virus genomic approaches to more comprehensively explore viral communities in nature.",2019 Apr 25,"['Warwick-Dugdale, Joanna', 'Solonenko, Natalie', 'Moore, Karen', 'Chittick, Lauren', 'Gregory, Ann C.', 'Allen, Michael J.', 'Sullivan, Matthew B.', 'Temperton, Ben']",PeerJ,,,True
6c77e52c219726553c3c5ad9b5ed3e6c41b71f73,PMC,Long-read viral metagenomics captures abundant and microdiverse viral populations and their niche-defining genomic islands,http://dx.doi.org/10.7717/peerj.6800,PMC6487183,31086738,CC BY,"Marine viruses impact global biogeochemical cycles via their influence on host community structure and function, yet our understanding of viral ecology is constrained by limitations in host culturing and a lack of reference genomes and ‘universal’ gene markers to facilitate community surveys. Short-read viral metagenomic studies have provided clues to viral function and first estimates of global viral gene abundance and distribution, but their assemblies are confounded by populations with high levels of strain evenness and nucleotide diversity (microdiversity), limiting assembly of some of the most abundant viruses on Earth. Such features also challenge assembly across genomic islands containing niche-defining genes that drive ecological speciation. These populations and features may be successfully captured by single-virus genomics and fosmid-based approaches, at least in abundant taxa, but at considerable cost and technical expertise. Here we established a low-cost, low-input, high throughput alternative sequencing and informatics workflow to improve viral metagenomic assemblies using short-read and long-read technology. The ‘VirION’ (Viral, long-read metagenomics via MinION sequencing) approach was first validated using mock communities where it was found to be as relatively quantitative as short-read methods and provided significant improvements in recovery of viral genomes. We then then applied VirION to the first metagenome from a natural viral community from the Western English Channel. In comparison to a short-read only approach, VirION: (i) increased number and completeness of assembled viral genomes; (ii) captured abundant, highly microdiverse virus populations, and (iii) captured more and longer genomic islands. Together, these findings suggest that VirION provides a high throughput and cost-effective alternative to fosmid and single-virus genomic approaches to more comprehensively explore viral communities in nature.",2019 Apr 25,"['Warwick-Dugdale, Joanna', 'Solonenko, Natalie', 'Moore, Karen', 'Chittick, Lauren', 'Gregory, Ann C.', 'Allen, Michael J.', 'Sullivan, Matthew B.', 'Temperton, Ben']",PeerJ,,,False
2d9d85a9897d69430aadcde5a2b3c62d982280d9,PMC,Long-read viral metagenomics captures abundant and microdiverse viral populations and their niche-defining genomic islands,http://dx.doi.org/10.7717/peerj.6800,PMC6487183,31086738,CC BY,"Marine viruses impact global biogeochemical cycles via their influence on host community structure and function, yet our understanding of viral ecology is constrained by limitations in host culturing and a lack of reference genomes and ‘universal’ gene markers to facilitate community surveys. Short-read viral metagenomic studies have provided clues to viral function and first estimates of global viral gene abundance and distribution, but their assemblies are confounded by populations with high levels of strain evenness and nucleotide diversity (microdiversity), limiting assembly of some of the most abundant viruses on Earth. Such features also challenge assembly across genomic islands containing niche-defining genes that drive ecological speciation. These populations and features may be successfully captured by single-virus genomics and fosmid-based approaches, at least in abundant taxa, but at considerable cost and technical expertise. Here we established a low-cost, low-input, high throughput alternative sequencing and informatics workflow to improve viral metagenomic assemblies using short-read and long-read technology. The ‘VirION’ (Viral, long-read metagenomics via MinION sequencing) approach was first validated using mock communities where it was found to be as relatively quantitative as short-read methods and provided significant improvements in recovery of viral genomes. We then then applied VirION to the first metagenome from a natural viral community from the Western English Channel. In comparison to a short-read only approach, VirION: (i) increased number and completeness of assembled viral genomes; (ii) captured abundant, highly microdiverse virus populations, and (iii) captured more and longer genomic islands. Together, these findings suggest that VirION provides a high throughput and cost-effective alternative to fosmid and single-virus genomic approaches to more comprehensively explore viral communities in nature.",2019 Apr 25,"['Warwick-Dugdale, Joanna', 'Solonenko, Natalie', 'Moore, Karen', 'Chittick, Lauren', 'Gregory, Ann C.', 'Allen, Michael J.', 'Sullivan, Matthew B.', 'Temperton, Ben']",PeerJ,,,False
1da61ea537e7b6a6b56a2ac371e9e95442078672,PMC,"Infectious bronchitis virus from chickens in Al-Hasa, Saudi Arabia 2015-2016",http://dx.doi.org/10.14202/vetworld.2019.424-433,PMC6487242,31089313,CC BY,"AIM: This study aimed to isolate some of the currently circulating infectious bronchitis virus (IBV) strains from some broiler chicken farms in Al-Hasa and to do some molecular characteristics of these strains. MATERIALS AND METHODS: We collected 300 tissue specimens, including the trachea, bronchi, lungs, and kidneys from some four commercial chicken farms showing respiratory manifestations. We tested these tissue specimens by the real-time polymerase chain reaction (RT-PCR) and gel-based PCR. We selected some PCR positive samples for isolation in the embryonated chicken eggs (ECE). We sequenced some PCR-positive samples and conducted phylogenetic analysis based on the obtained sequences. RESULTS: Our molecular surveillance revealed that 31.6% of the tested specimens were IBV positive by PCR. We selected some positive specimens showing low Ct values by the qRT-PCR for virus isolation by the ECE. The infected eggs showed hemorrhage, dwarfing, and death in some cases after three passages in the ECE. We sequenced some of the positive PCR specimens and used the obtained sequences to draw the phylogenetic tree based on the partial IBV-ORF-1a, N, and S1 gene sequences. The phylogenetic trees based on the IBV-N and S1 gene sequences showed that the circulating IBV strains in Al-Hasa during 2016 was showing a high degree of identity to some strains from Taiwan and Italy. Meanwhile, the grouping of these strains based on the IBV-S1 sequences revealed that the currently circulating IBV strains in Al-Hasa belonged to Gr.I.7 along with strains from Taiwan. CONCLUSION: Our results confirmed the continuous circulation of the IBV among the chicken population in Al-Hasa despite the intensive application of vaccines against this virus.",2019 Mar 19,"['Alsultan, Musaed Abdulaziz', 'Alhammadi, Mohamed Ali', 'Hemida, Maged Gomaa']",Vet World,,,True
e1ea07d20c6b64c1eae05319f1f66f729f2583d9,PMC,Efficacy of traditional Chinese medication Tangminling pill in Chinese patients with type 2 diabetes,http://dx.doi.org/10.1042/BSR20181729,PMC6488948,30948503,CC BY,"The morbidity of type 2 diabetes mellitus (T2DM) has been increasing rapidly worldwide. Tangminling pill, consisting of ten Chinese herbal medications, is usually prescribed for T2DM in mainland China. Whether treatment with Tangminling can improve clinical outcomes of T2DM patients was still debated. Four studies comparing Tangminling vs. placebo treatment in T2DM patients were included and 767 T2DM patients were enrolled in our analyses. Tangminling treatment exhibited better efficacy than placebo in reducing hemoglobin A1c (HbA1c) (1.11 vs. 0.32%; pooled weighted mean difference [WMD]: 0.80; 95% confidence interval [CI]: 0.65–0.96; P<0.001), fasting plasma glucose (0.82 vs. −0.40 mM; WMD: 1.10; 95% CI: 0.56–1.64; P<0.001), 2-h postprandial glucose (2-hr PG) (2.81 vs. 1.11 mM; WMD: 1.80; 95% CI: 1.72–1.88; P<0.001), homeostatic model assessment-β level (4.28 vs. 0.41; WMD: 0.44; 95% CI: 0.27–0.61; P<0.001), waist circumference (WC) (1.04 vs. 0.36 cm; WMD: 0.78; 95% CI: 0.37–1.19; P<0.001) and body weight index (0.37 vs. 0.11 kg/m(2); WMD: 0.30; 95% CI: −0.00 to 0.61; P=0.05). Tangminling pill might reduce glucose level and body weight and improve β-cell function in T2DM patients. Our study highlights the important role of Tangminling pill in the management of T2DM.",2019 Apr 30,"['Cheng, Jing', 'Zheng, Jia', 'Liu, Yanping', 'Hao, Panpan']",Biosci Rep,,,True
636fb28e842b058bff497388c5444fc1f53cb61c,PMC,Biochemical characterization of recombinant Avihepatovirus 3C protease and its localization,http://dx.doi.org/10.1186/s12985-019-1155-3,PMC6489322,31036013,CC BY,"BACKGROUND: The picornaviral 3C protease mediates viral polyprotein maturation and multiple cleavages of host proteins to modulate viral translation and transcription. The 3C protease has been regarded as a valid target due to its structural similarity among different picornaviruses and minimal sequence similarity with host proteins; therefore, the development of potent inhibitors against the 3C protease as an antiviral drug is ongoing. Duck hepatitis A virus (DHAV) belongs to the Picornavidea family and is a major threat to the poultry industry. To date, little is known about the roles of the DHAV 3C protease plays during infection. METHODS: In this study, we compared the full-length DHAV 3C protein sequence with other 3C sequences to obtain an alignment for the construction of a phylogenetic tree. Then, we expressed and purified recombinant DHAV 3C protease in the BL21 expression system using nickel-NTA affinity chromatography. The optimization of the cleavage assay conditions and the kinetic analysis for DHAV 3C protease were done by in vitro cleavage assays with a fluorogenic peptide respectively. The inhibitory activity of rupintrivir against the DHAV 3C protease was further evaluated. The localization of the 3C protease in infected and transfected cells was determined using immunofluorescence and confocal microscopy. RESULTS: Under different expression conditions, the 3C protease was found to be highly expressed after induction with 1 mM IPTG at 16 °C for 10 h. We synthesized a fluorogenic peptide derived from the cleavage site of the DHAV polyprotein and evaluated the protease activity of the DHAV 3C protease for the first time. We used fluorimetric based kinetic analysis to determine kinetic parameters, and V(max) and K(m) values were determined to be 16.52 nmol/min and 50.78 μM, respectively. Rupintrivir was found to exhibit inhibitory activity against the DHAV 3C protease. Using polyclonal antibody and an indirect immunofluorescence microscopy assay (IFA), it was determined that the DHAV 3C protease was found in the nucleus during infection. In addition, the DHAV 3C protease can enter into the nucleus without the cooperation of viral proteins. CONCLUSIONS: This is the first study to examine the activity of the DHAV 3C protease, and the activity of the DHAV 3C protease is temperature-, pH- and NaCl concentration- dependent. The DHAV 3C protease localizes throughout DHAV-infected cells and can enter into the nucleus in the absence of other viral proteins. The kinetic analysis was calculated, and the V(max) and K(m) values were 16.52 nmol/min and 50.78 μM, respectively, using the Lineweaver–Burk plot.",2019 Apr 29,"['Sun, Di', 'Wang, Mingshu', 'Wen, Xingjian', 'Mao, Sai', 'Cheng, Anchun', 'Jia, Renyong', 'Yang, Qiao', 'Wu, Ying', 'Zhu, Dekang', 'Chen, Shun', 'Liu, Mafeng', 'Zhao, Xinxin', 'Zhang, Shaqiu', 'Chen, Xiaoyue', 'Liu, Yunya', 'Yu, Yanling', 'Zhang, Ling']",Virol J,,,True
11ae714b01d105e39919f2a6d9b2471153963d25,PMC,Overcrowding in a neonatal intermediate care unit: impact on the incidence of multidrug-resistant gram-negative organisms,http://dx.doi.org/10.1186/s12879-019-3981-8,PMC6489334,31035966,CC BY,"BACKGROUND: Overcrowding, reduced nurse to patient ratio, limited distance between incubators and absence of microbiological surveillance have been shown to promote spread of multidrug-resistant gram-negative organisms (MDRGN) in patients with birthweight < 1500 g. Patients > 1500 g treated on an intermediate care unit are unrepresented in recent literature. We therefore intended to present data obtained from a short-term overcrowded neonatal intermediate care unit (NIMCU) at a level III (international categorization) perinatal center at University Hospital Frankfurt, Germany. METHODS: During a 25 day overcrowding (OV) and 28 day post-overcrowding period (POST-OV) on NIMCU, epidemiological data obtained from continuously hold microbiological surveillance were investigated and compared to the last 12 months of ward-regular bed occupancy preceding OV (PRAE-OV). RESULTS: During OV, the number of patients simultaneously treated at the NIMCU increased from 18 to 22, resulting in a reduced bed-to-bed space. Nurse: patient ratio was 4:22 during OV compared to 3:18 during PRAE-OV. Cumulative incidence of MDRGN was 4.7% in OV and 2.4% POST-OV compared to 4.8% to PRAE-OV, respectively, without any significant variations. During OV and POST-OV, septic episodes due to MDRGN were not observed. In one case, potential nosocomial transmission of Enterobacter cloacae resistant to Piperacillin and 3rd/4th generation cephalosporins was observed. CONCLUSIONS: Prevention of nosocomial spread of MDRGN in an overcrowded NIMCU is based on staff’s diligent training and adequate staffing. Concise microbiological surveillance should be guaranteed to escort through overcrowding periods. In our setting, impact of bed-to-bed distance on MDRGN transmission seemed to be less strong.",2019 Apr 29,"['Fischer, Doris', 'Schlößer, Rolf L.', 'Kempf, Volkhard A. J.', 'Wichelhaus, Thomas A.', 'Klingebiel, Thomas', 'Philippi, Sabine', 'Falgenhauer, Linda', 'Imirzalioglu, Can', 'Dahl, Udo', 'Brandt, Christian', 'Reinheimer, Claudia']",BMC Infect Dis,,,True
359417eec03774de55b638845646f0f377f35de8,PMC,"Factors associated with chronic obstructive pulmonary disease exacerbation, based on big data analysis",http://dx.doi.org/10.1038/s41598-019-43167-w,PMC6491439,31040338,CC BY,"Preventing exacerbation in chronic obstructive pulmonary disease (COPD) patients is crucial, but requires identification of the exacerbating factors. To date, no integrated analysis of patient-derived and external factors has been reported. To identify factors associated with COPD exacerbation, we collected data, including smoking status, lung function, and COPD assessment test scores, from 594 COPD patients in the Korean COPD subgroup study (KOCOSS), and merged these data with patients’ Korean Health Insurance Review and Assessment Service data for 2007–2012. We also collected primary weather variables, including levels of particulate matter <10 microns in diameter, daily minimum ambient temperature, as well as respiratory virus activities, and the logs of web queries on COPD-related issues. We then assessed the associations between these patient-derived and external factors and COPD exacerbations. Univariate analysis showed that patient factors, air pollution, various types of viruses, temperature, and the number of COPD-related web queries were associated with COPD exacerbation. Multivariate analysis revealed that the number of exacerbations in the preceding year, female sex, COPD grade, and influenza virus detection rate, and lowest temperature showed significant association with exacerbation. Our findings may help COPD patients predict when exacerbations are likely, and provide intervention as early as possible.",2019 Apr 30,"['Lee, Jongmin', 'Jung, Hyun Myung', 'Kim, Sook Kyung', 'Yoo, Kwang Ha', 'Jung, Ki-Suck', 'Lee, Sang Haak', 'Rhee, Chin Kook']",Sci Rep,,,True
954a68177fd22cbb6f2dc0710b236c10731357bf,PMC,Comparative analysis of serologic cross-reactivity using convalescent sera from filovirus-experimentally infected fruit bats,http://dx.doi.org/10.1038/s41598-019-43156-z,PMC6491471,31040343,CC BY,"With the exception of Reston and Bombali viruses, the marburgviruses and ebolaviruses (family Filoviridae) cause outbreaks of viral hemorrhagic fever in sub-Saharan Africa. The Egyptian rousette bat (ERB) is a natural reservoir host for the marburgviruses and evidence suggests that bats are also natural reservoirs for the ebolaviruses. Although the search for the natural reservoirs of the ebolaviruses has largely involved serosurveillance of the bat population, there are no validated serological assays to screen bat sera for ebolavirus-specific IgG antibodies. Here, we generate filovirus-specific antisera by prime-boost immunization of groups of captive ERBs with all seven known culturable filoviruses. After validating a system of filovirus-specific indirect ELISAs utilizing infectious-based virus antigens for detection of virus-specific IgG antibodies from bat sera, we assess the level of serological cross-reactivity between the virus-specific antisera and heterologous filovirus antigens. This data is then used to generate a filovirus antibody fingerprint that can predict which of the filovirus species in the system is most antigenically similar to the species responsible for past infection. Our filovirus IgG indirect ELISA system will be a critical tool for identifying bat species with high ebolavirus seroprevalence rates to target for longitudinal studies aimed at establishing natural reservoir host-ebolavirus relationships.",2019 Apr 30,"['Schuh, Amy J.', 'Amman, Brian R.', 'Sealy, Tara S.', 'Flietstra, Timothy D.', 'Guito, Jonathan C.', 'Nichol, Stuart T.', 'Towner, Jonathan S.']",Sci Rep,,,False
9683ced158e728a9be859ddbeaf2930584e4dea8,PMC,Comparative analysis of serologic cross-reactivity using convalescent sera from filovirus-experimentally infected fruit bats,http://dx.doi.org/10.1038/s41598-019-43156-z,PMC6491471,31040343,CC BY,"With the exception of Reston and Bombali viruses, the marburgviruses and ebolaviruses (family Filoviridae) cause outbreaks of viral hemorrhagic fever in sub-Saharan Africa. The Egyptian rousette bat (ERB) is a natural reservoir host for the marburgviruses and evidence suggests that bats are also natural reservoirs for the ebolaviruses. Although the search for the natural reservoirs of the ebolaviruses has largely involved serosurveillance of the bat population, there are no validated serological assays to screen bat sera for ebolavirus-specific IgG antibodies. Here, we generate filovirus-specific antisera by prime-boost immunization of groups of captive ERBs with all seven known culturable filoviruses. After validating a system of filovirus-specific indirect ELISAs utilizing infectious-based virus antigens for detection of virus-specific IgG antibodies from bat sera, we assess the level of serological cross-reactivity between the virus-specific antisera and heterologous filovirus antigens. This data is then used to generate a filovirus antibody fingerprint that can predict which of the filovirus species in the system is most antigenically similar to the species responsible for past infection. Our filovirus IgG indirect ELISA system will be a critical tool for identifying bat species with high ebolavirus seroprevalence rates to target for longitudinal studies aimed at establishing natural reservoir host-ebolavirus relationships.",2019 Apr 30,"['Schuh, Amy J.', 'Amman, Brian R.', 'Sealy, Tara S.', 'Flietstra, Timothy D.', 'Guito, Jonathan C.', 'Nichol, Stuart T.', 'Towner, Jonathan S.']",Sci Rep,,,True
360ab35f1a888c57572270161254de77913951be,PMC,Stage of Gestation at Porcine Epidemic Diarrhea Virus Infection of Pregnant Swine Impacts Maternal Immunity and Lactogenic Immune Protection of Neonatal Suckling Piglets,http://dx.doi.org/10.3389/fimmu.2019.00727,PMC6491507,31068924,CC BY,"During pregnancy, the maternal immune response changes dramatically over the course of gestation. This has implications for generation of lactogenic immunity and subsequent protection in suckling neonates against enteric viral infections. For example, porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus that causes acute diarrhea in neonatal piglets. Due to the high virulence of PEDV and the naïve, immature immune system of neonatal suckling piglets, passive lactogenic immunity to PEDV induced during pregnancy, via the gut-mammary gland (MG)-secretory IgA (sIgA) axis, is critical for piglet protection. However, the anti-PEDV immune response during pregnancy and stage of gestation required to optimally stimulate the gut-MG-sIgA axis is undefined. We hypothesize that there is a gestational window in which non-lethal PEDV infection of pregnant gilts influences maximum lymphocyte mucosal trafficking to the MG, resulting in optimal passive lactogenic protection in suckling piglets. To understand how the stages of gestation affect maternal immune responses to PEDV, three groups of gilts were orally infected with PEDV in the first, second or third trimester. Control (mock) gilts were inoculated with medium in the third trimester. To determine if lactogenic immunity correlated with protection, all piglets were PEDV-challenged at 3–5 days postpartum. PEDV infection of gilts at different stages of gestation significantly affected multiple maternal systemic immune parameters prepartum, including cytokines, B cells, PEDV antibodies (Abs), and PEDV antibody secreting cells (ASCs). Pregnant second trimester gilts had significantly higher levels of circulating PEDV IgA and IgG Abs and ASCs and PEDV virus neutralizing (VN) Abs post PEDV infection. Coinciding with the significantly higher PEDV Ab responses in second trimester gilts, the survival rate of their PEDV-challenged piglets was 100%, compared with 87.2, 55.9, and 5.7% for first, third, and mock litters, respectively. Additionally, piglet survival positively correlated with PEDV IgA Abs and ASCs and VN Abs in milk and PEDV IgA and IgG Abs in piglet serum. Our findings have implications for gestational timing of oral attenuated PEDV maternal vaccines, whereby PEDV intestinal infection in the second trimester optimally stimulated the gut-MG-sIgA axis resulting in 100% lactogenic immune protection in suckling piglets.",2019 Apr 24,"['Langel, Stephanie N.', 'Paim, Francine C.', 'Alhamo, Moyasar A.', 'Buckley, Alexandra', 'Van Geelen, Albert', 'Lager, Kelly M.', 'Vlasova, Anastasia N.', 'Saif, Linda J.']",Front Immunol,,,True
620831ad78fde11d52ab3119bb3a524a8e74628d,PMC,Masters of manipulation: Viral modulation of the immunological synapse,http://dx.doi.org/10.1111/cmi.12944,PMC6492149,30123959,CC BY,"In order to thrive, viruses have evolved to manipulate host cell machinery for their own benefit. One major obstacle faced by pathogens is the immunological synapse. To enable efficient replication and latency in immune cells, viruses have developed a range of strategies to manipulate cellular processes involved in immunological synapse formation to evade immune detection and control T‐cell activation. In vitro, viruses such as human immunodeficiency virus 1 and human T‐lymphotropic virus type 1 utilise structures known as virological synapses to aid transmission of viral particles from cell to cell in a process termed trans‐infection. The formation of the virological synapse provides a gateway for virus to be transferred between cells avoiding the extracellular space, preventing antibody neutralisation or recognition by complement. This review looks at how viruses are able to subvert intracellular signalling to modulate immune function to their advantage and explores the role synapse formation has in viral persistence and cell‐to‐cell transmission.",2018 Oct 21,"['Bayliss, Rebecca J.', 'Piguet, Vincent']",Cell Microbiol,,,True
63c5c1f61a3aadefcb0e9c01bc4e67cc0a99d8f2,PMC,Demographic and seasonal characteristics of respiratory pathogens in neonates and infants aged 0 to 12 months in the Central‐East region of Tunisia,http://dx.doi.org/10.1002/jmv.25347,PMC6492255,30351487,CC BY,"BACKGROUND: This study aimed to characterize the epidemiology of pathogenic respiratory agents in patients aged 0 to 12 months and hospitalized for acute respiratory infections in Tunisia between 2013 and 2014. METHODS: A total of 20 pathogens, including viruses, Mycoplasma pneumoniae, and Streptococcus pneumoniae, were detected using molecular sensitive assays, and their associations with the patient’s demographic data and season were analyzed. RESULTS: Viral infectious agents were found in 449 (87.2%) of 515 specimens. Dual and multiple infectious agents were detected in 31.4% and 18.6% of the samples, respectively. Viral infection was predominant in the pediatric environment (90.8%, P < 0.001), male patients (88.0%), and spring (93.8%). Rhinovirus was the most detected virus (51.8%) followed by respiratory syncytial virus A/B (34.4%), coronavirus group (18.5%), adenovirus (17.9%), and parainfluenza viruses 1‐4 (10.9%). Respiratory Syncytial virus A/B was significantly associated with gender (38.0% male cases vs 28.3% female cases, P = 0.02). Infections by Adenovirus, Bocavirus, and Metapneumovirus A/B increased with increasing age of patients (predominated cases aged 6‐12 months, P < 0.001). S. pneumoniae was detected in 30.9% of th tested samples. In 18.2% of the negative viral infections, only S. pneumoniae was identified. CONCLUSION: A predominance of the rhinovirus infection was observed in this study. Coronavirus subtypes were described for the first time in Tunisia. The observed different pathogenic profiles across age groups could be helpful to avoid the misclassification of patients presenting with ARIs at the triage level when no standardized protocol is available. This study will provide clues for physicians informing decisions regarding preventive strategies and medication in Tunisia.",2019 Apr 21,"['Brini Khalifa, Ines', 'Hannachi, Naila', 'Guerrero, Aida', 'Orth‐Höller, Dorothea', 'Bhiri, Sana', 'Bougila, Jihene', 'Boughamoura, Lamia', 'Merchaoui, Sonia Nouri', 'Sboui, Hassen', 'Mahdhaoui, Nabiha', 'Schiela, Britta', 'Laer, Dorothee Holm‐von', 'Boukadida, Jalel', 'Stoiber, Heribert']",J Med Virol,,,True
1d44b78805f7baf17f811f8e5957c546c020abbc,PMC,Breastfeeding and Respiratory Infections in the First 6 Months of Life: A Case Control Study,http://dx.doi.org/10.3389/fped.2019.00152,PMC6492465,31106183,CC BY,"Background: Viral respiratory tract infections (VRI) are a major reason for hospitalization in children younger than 5 years. A case control study was conducted to investigate the potential role of breastfeeding in protecting children <1 year of age from VRI. Methods: Patients admitted for a respiratory tract infections routinely underwent a nasopharyngeal aspirate, which was tested with an RT-PCR for 14 respiratory viruses. Hospitalized infants positive for viruses were enrolled as cases; healthy controls were enrolled among patients admitted for ultrasound hip screening. The effect of breastfeeding on pertussis was investigated through multivariable analysis. Results: We enrolled a total of 496 patients: 238 cases and 258 healthy controls. Among cases, eighty-six patients (36.1%) had a rinovirus, 78 (32.8%) an RSV, 22 (9.2%) an adenovirus, and 37 (15.5%) a coinfections with multiple viruses. The number of households was significantly higher in cases (mean in cases 4.5; mean 3.7 in controls, p < 0.001) and the proportion of infants having siblings (79% in cases vs. 43% in controls, p < 0.001). Proportion of smoking mothers was higher in cases than in controls (21.4 vs. 10.1%, p = 0.001). Among cases 44.5% were exclusively breastfed at symptoms onset vs. 48.8% of healthy controls. According to the multivariable analysis, being exclusively breastfed at symptom onset was associated with a higher risk of viral respiratory infection (3.7; 95% CI 1.64–8.41), however a longer breastfeeding duration was protective (OR 0.98; 95% CI 0.97–0.99). Also having at least one sibling was associated to a higher risk (OR 3.6; 95% CI 2.14–5.92) as well as having a smoking mother (OR 2.6; 95% CI 1.33–4.89). Conclusions: Breastfeeding remains a mainstay of prevention for numerous diseases and its protective role increases with duration. However, being breastfed when mothers carry a respiratory infection may increase the risk of transmission, acting as a proxy for closer contacts. In future studies, potential confounding variables as pattern of contacts with other individuals, should be taken into account.",2019 Apr 24,"['Pandolfi, Elisabetta', 'Gesualdo, Francesco', 'Rizzo, Caterina', 'Carloni, Emanuela', 'Villani, Alberto', 'Concato, Carlo', 'Linardos, Giulia', 'Russo, Luisa', 'Ferretti, Beatrice', 'Campagna, Ilaria', 'Tozzi, Alberto']",Front Pediatr,,,True
ec0528e8df97c81c3e94673e83bf614c09090cf1,PMC,Detection of dicistroviruses RNA in blood of febrile Tanzanian children,http://dx.doi.org/10.1080/22221751.2019.1603791,PMC6493270,30999808,CC BY,"Fever is the leading cause of paediatric outpatient consultations in Sub-Saharan Africa. Although most are suspected to be of viral origin, a putative causative pathogen is not identified in over a quarter of these febrile episodes. Using a de novo assembly sequencing approach, we report the detection (15.4%) of dicistroviruses (DicV) RNA in sera collected from 692 febrile Tanzanian children. In contrast, DicV RNA was only detected in 1/77 (1.3%) plasma samples from febrile Tanzanian adults, suggesting that children could represent the primary susceptible population. Estimated viral load by specific quantitative real-time RT–PCR assay ranged from < 1.32E3 to 1.44E7 viral RNA copies/mL serum. Three DicV full-length genomes were obtained, and a phylogenetic analyse on the capsid region showed the presence of two clusters representing tentative novel genus. Although DicV-positive cases were detected throughout the year, a significantly higher positivity rate was observed during the rainy season. This study reveals that novel DicV RNA is frequently detected in the blood of Tanzanian children, paving the way for further investigations to determine if DicV possibly represent a new agent in humans.",2019 Apr 19,"['Cordey, Samuel', 'Laubscher, Florian', 'Hartley, Mary-Anne', 'Junier, Thomas', 'Pérez-Rodriguez, Francisco J.', 'Keitel, Kristina', 'Vieille, Gael', 'Samaka, Josephine', 'Mlaganile, Tarsis', 'Kagoro, Frank', 'Boillat-Blanco, Noémie', 'Mbarack, Zainab', 'Docquier, Mylène', 'Brito, Francisco', 'Eibach, Daniel', 'May, Jürgen', 'Sothmann, Peter', 'Aldrich, Cassandra', 'Lusingu, John', 'Tapparel, Caroline', 'D’Acremont, Valérie', 'Kaiser, Laurent']",Emerg Microbes Infect,,,True
22b6ca03f6a90e0a2aa2fb3e539bae9b799407f8,PMC,Consequences of Pathogen Lists: Why Some Diseases May Continue to Plague Us,http://dx.doi.org/10.4269/ajtmh.18-0801,PMC6493960,30652662,CC BY,"The current strategy used by many funding agencies for determining how money is spent on research to help prevent infectious disease outbreaks is based on pathogen-specific priority lists. Listing disease threats provides focus for business and research planning conducive to specific goals of developing a drug, or a vaccine, or other particular product. But, this singular type of focus has consequences. This perspective explores the consequences of lists, and describes how parallel programming independent of disease lists that address what we need to do to prevent and mitigate emerging disease risks may provide benefits out of reach of a singular focus on what products we need to have.",2019 May 14,"['Brett-Major, David M.', 'Racine, Trina', 'Kobinger, Gary P.']",Am J Trop Med Hyg,,,False
034ad50caefc406811a792c51ff23b39a15bfd6e,PMC,"Computational prediction and in vitro validation of VEGFR1 as a novel protein target for 2,3,7,8-tetrachlorodibenzo-p-dioxin",http://dx.doi.org/10.1038/s41598-019-43232-4,PMC6497656,31048752,CC BY,"The toxic manifestations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant, primarily depend on its ability to activate aryl hydrocarbon receptor (AhR), which is a ligand-dependent transcription factor belonging to the superfamily of basic-helix-loop-helix DNA-binding proteins. In the present study, we aimed to identify novel protein receptor targets for TCDD using computational and in vitro validation experiments. Interestingly, results from computational methods predicted that Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) could be one of the potential targets for TCDD in both mouse and humans. Results from molecular docking studies showed that human VEGFR1 (hVEGFR1) has less affinity towards TCDD compared to the mouse VEGFR1 (mVEGFR1). In vitro validation results showed that TCDD can bind and phosphorylate hVEGFR1. Further, results from molecular dynamic simulation studies showed that hVEGFR1 interaction with TCDD is stable throughout the simulation time. Overall, the present study has identified VEGFR1 as a novel target for TCDD, which provides the basis for further elucidating the role of TCDD in angiogenesis.",2019 May 2,"['Chitrala, Kumaraswamy Naidu', 'Yang, Xiaoming', 'Busbee, Brandon', 'Singh, Narendra P.', 'Bonati, Laura', 'Xing, Yongna', 'Nagarkatti, Prakash', 'Nagarkatti, Mitzi']",Sci Rep,,,False
fd0802a5e13561915fb90cbfe5bb12a751197e28,PMC,"Computational prediction and in vitro validation of VEGFR1 as a novel protein target for 2,3,7,8-tetrachlorodibenzo-p-dioxin",http://dx.doi.org/10.1038/s41598-019-43232-4,PMC6497656,31048752,CC BY,"The toxic manifestations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant, primarily depend on its ability to activate aryl hydrocarbon receptor (AhR), which is a ligand-dependent transcription factor belonging to the superfamily of basic-helix-loop-helix DNA-binding proteins. In the present study, we aimed to identify novel protein receptor targets for TCDD using computational and in vitro validation experiments. Interestingly, results from computational methods predicted that Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) could be one of the potential targets for TCDD in both mouse and humans. Results from molecular docking studies showed that human VEGFR1 (hVEGFR1) has less affinity towards TCDD compared to the mouse VEGFR1 (mVEGFR1). In vitro validation results showed that TCDD can bind and phosphorylate hVEGFR1. Further, results from molecular dynamic simulation studies showed that hVEGFR1 interaction with TCDD is stable throughout the simulation time. Overall, the present study has identified VEGFR1 as a novel target for TCDD, which provides the basis for further elucidating the role of TCDD in angiogenesis.",2019 May 2,"['Chitrala, Kumaraswamy Naidu', 'Yang, Xiaoming', 'Busbee, Brandon', 'Singh, Narendra P.', 'Bonati, Laura', 'Xing, Yongna', 'Nagarkatti, Prakash', 'Nagarkatti, Mitzi']",Sci Rep,,,True
57197f5ee8bd40e26cf5e08f825621755d2612d5,PMC,Guinea Fowl Coronavirus Diversity Has Phenotypic Consequences for Glycan and Tissue Binding,http://dx.doi.org/10.1128/JVI.00067-19,PMC6498037,30842318,CC BY,"Guinea fowl coronavirus (GfCoV) causes fulminating enteritis that can result in a daily death rate of 20% in guinea fowl flocks. Here, we studied GfCoV diversity and evaluated its phenotypic consequences. Over the period of 2014 to 2016, affected guinea fowl flocks were sampled in France, and avian coronavirus presence was confirmed by PCR on intestinal content and immunohistochemistry of intestinal tissue. Sequencing revealed 89% amino acid identity between the viral attachment protein S1 of GfCoV/2014 and that of the previously identified GfCoV/2011. To study the receptor interactions as a determinant for tropism and pathogenicity, recombinant S1 proteins were produced and analyzed by glycan and tissue arrays. Glycan array analysis revealed that, in addition to the previously elucidated biantennary di-N-acetyllactosamine (diLacNAc) receptor, viral attachment S1 proteins from GfCoV/2014 and GfCoV/2011 can bind to glycans capped with alpha-2,6-linked sialic acids. Interestingly, recombinant GfCoV/2014 S1 has an increased affinity for these glycans compared to that of GfCoV/2011 S1, which was in agreement with the increased avidity of GfCoV/2014 S1 for gastrointestinal tract tissues. Enzymatic removal of receptors from tissues before application of spike proteins confirmed the specificity of S1 tissue binding. Overall, we demonstrate that diversity in GfCoV S1 proteins results in differences in glycan and tissue binding properties. IMPORTANCE Avian coronaviruses cause major global problems in the poultry industry. As causative agents of huge economic losses, the detection and understanding of the molecular determinants of viral tropism are of ultimate importance. Here, we set out to study those parameters and obtained in-depth insight into the virus-host interactions of guinea fowl coronavirus (GfCoV). Our data indicate that diversity in GfCoV viral attachment proteins results in differences in degrees of affinity for glycan receptors, as well as altered avidity for intestinal tract tissues, which might have consequences for GfCoV tissue tropism and pathogenesis in guinea fowls.",2019 May 1,"['Bouwman, Kim M.', 'Delpont, Mattias', 'Broszeit, Frederik', 'Berger, Renaud', 'Weerts, Erik A. W. S.', 'Lucas, Marie-Noëlle', 'Delverdier, Maxence', 'Belkasmi, Sakhia', 'Papanikolaou, Andreas', 'Boons, Geert-Jan', 'Guérin, Jean-Luc', 'de Vries, Robert P.', 'Ducatez, Mariette F.', 'Verheije, Monique H.']",J Virol,,,True
8812b0579ea75d59a8dca6407431a3f716728556,PMC,Quantitative Proteomic Analysis Reveals Unfolded-Protein Response Involved in Severe Fever with Thrombocytopenia Syndrome Virus Infection,http://dx.doi.org/10.1128/JVI.00308-19,PMC6498065,30842332,CC BY,"Severe fever with thrombocytopenia syndrome (SFTS) is an emerging, highly pathogenic, infectious disease caused by infection with a newly discovered tick-borne phlebovirus, SFTS virus (SFTSV). Limited information on the molecular mechanism of SFTSV infection and pathogenesis impedes the development of effective vaccines and drugs for SFTS prevention and treatment. In this study, an isobaric tag for relative and absolute quantification (iTRAQ)-based quantitative proteomic analysis of SFTSV-infected HEK 293 cells was performed to explore dynamic host cellular protein responses toward SFTSV infection. A total of 433 of 5,606 host proteins involved in different biological processes were differentially regulated by SFTSV infection. The proteomic results highlighted a potential role of endoplasmic reticular stress-triggered unfolded-protein response (UPR) in SFTSV infection. Further functional studies confirmed that all three major branches of the UPR, including the PKR-like endoplasmic reticulum kinase (PERK), the activating transcription factor-6 (ATF6), and the inositol-requiring protein-1 (IRE1)/X-box-binding protein 1 (XBP1) pathways, were activated by SFTSV. However, only the former two pathways play a crucial role in SFTSV infection. Furthermore, expression of SFTSV glycoprotein (GP) alone was sufficient to stimulate the UPR, whereas suppression of PERK and ATF6 notably decreased GP expression. Interestingly, two other newly discovered phleboviruses, Heartland virus and Guertu virus, also stimulated the UPR, suggesting a common mechanism shared by these genetically related phleboviruses. This study provides a global view to our knowledge on how host cells respond to SFTSV infection and highlights that host cell UPR plays an important role in phlebovirus infection. IMPORTANCE Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe fever with thrombocytopenia syndrome in humans, with a mortality rate reaching up to 30% in some outbreaks. There are currently no U.S. Food and Drug Administration-approved vaccines or specific antivirals available against SFTSV. To comprehensively understand the molecular interactions occurring between SFTSV and the host cell, we exploit quantitative proteomic approach to investigate the dynamic host cellular responses to SFTSV infection. The results highlight multiple biological processes being regulated by SFTSV infection. Among these, we focused on exploration of the mechanism of how SFTSV infection stimulates the host cell’s unfolded-protein response (UPR) and identified the UPR as a common feature shared by SFTSV-related new emerging phleboviruses. This study, for the first time to our knowledge, provides a global map for host cellular responses to SFTSV infection and highlighted potential host targets for further research.",2019 May 1,"['Zhang, Lei-Ke', 'Wang, Bo', 'Xin, Qilin', 'Shang, Weijuan', 'Shen, Shu', 'Xiao, Gengfu', 'Deng, Fei', 'Wang, Hualin', 'Hu, Zhihong', 'Wang, Manli']",J Virol,,,True
340036a465efeb78d0b0160bf6dddd2322f293ef,PMC,Quantitative Proteomic Analysis Reveals Unfolded-Protein Response Involved in Severe Fever with Thrombocytopenia Syndrome Virus Infection,http://dx.doi.org/10.1128/JVI.00308-19,PMC6498065,30842332,CC BY,"Severe fever with thrombocytopenia syndrome (SFTS) is an emerging, highly pathogenic, infectious disease caused by infection with a newly discovered tick-borne phlebovirus, SFTS virus (SFTSV). Limited information on the molecular mechanism of SFTSV infection and pathogenesis impedes the development of effective vaccines and drugs for SFTS prevention and treatment. In this study, an isobaric tag for relative and absolute quantification (iTRAQ)-based quantitative proteomic analysis of SFTSV-infected HEK 293 cells was performed to explore dynamic host cellular protein responses toward SFTSV infection. A total of 433 of 5,606 host proteins involved in different biological processes were differentially regulated by SFTSV infection. The proteomic results highlighted a potential role of endoplasmic reticular stress-triggered unfolded-protein response (UPR) in SFTSV infection. Further functional studies confirmed that all three major branches of the UPR, including the PKR-like endoplasmic reticulum kinase (PERK), the activating transcription factor-6 (ATF6), and the inositol-requiring protein-1 (IRE1)/X-box-binding protein 1 (XBP1) pathways, were activated by SFTSV. However, only the former two pathways play a crucial role in SFTSV infection. Furthermore, expression of SFTSV glycoprotein (GP) alone was sufficient to stimulate the UPR, whereas suppression of PERK and ATF6 notably decreased GP expression. Interestingly, two other newly discovered phleboviruses, Heartland virus and Guertu virus, also stimulated the UPR, suggesting a common mechanism shared by these genetically related phleboviruses. This study provides a global view to our knowledge on how host cells respond to SFTSV infection and highlights that host cell UPR plays an important role in phlebovirus infection. IMPORTANCE Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe fever with thrombocytopenia syndrome in humans, with a mortality rate reaching up to 30% in some outbreaks. There are currently no U.S. Food and Drug Administration-approved vaccines or specific antivirals available against SFTSV. To comprehensively understand the molecular interactions occurring between SFTSV and the host cell, we exploit quantitative proteomic approach to investigate the dynamic host cellular responses to SFTSV infection. The results highlight multiple biological processes being regulated by SFTSV infection. Among these, we focused on exploration of the mechanism of how SFTSV infection stimulates the host cell’s unfolded-protein response (UPR) and identified the UPR as a common feature shared by SFTSV-related new emerging phleboviruses. This study, for the first time to our knowledge, provides a global map for host cellular responses to SFTSV infection and highlighted potential host targets for further research.",2019 May 1,"['Zhang, Lei-Ke', 'Wang, Bo', 'Xin, Qilin', 'Shang, Weijuan', 'Shen, Shu', 'Xiao, Gengfu', 'Deng, Fei', 'Wang, Hualin', 'Hu, Zhihong', 'Wang, Manli']",J Virol,,,True
cc8e81f5fd3efda044a42e965278d17c58bb4ea6,PMC,"Analysis of the spike, ORF3, and nucleocapsid genes of porcine epidemic diarrhea virus circulating on Thai swine farms, 2011–2016",http://dx.doi.org/10.7717/peerj.6843,PMC6499054,31106060,CC BY,"Porcine epidemic diarrhea virus (PEDV) outbreaks on pig farms have caused significant economic loss in the swine industry since it was first reported in Thailand a decade ago. Anecdotal evidence suggests that PEDV is now endemic in this region, therefore genome information of circulating PEDV is important for molecular surveillance and evaluation of potential benefits of field vaccination. Here, we characterized PEDV infection on commercial Thai swine farms by screening 769 samples of feces and small intestinal contents from pigs with diarrhea between 2011 and 2016. Using reverse-transcription polymerase chain reaction targeting the spike (S) gene, 153 PEDV-positive samples were further subjected to analysis of the open reading frame 3 and nucleocapsid (N) genes. Comparison of 95 samples in which nucleotide sequencing was successfully obtained for all three genes revealed evolutionary diversity among the Thai PEDV strains. Phylogenetic analyses suggest that although some Thai strains changed little from years past, others resembled more closely to the recent strains reported in China. Interestingly, eight Thai PEDV strains possessed amino acid deletions in the N protein. The PEDV sequence divergence may be responsible for driving periodic outbreaks and continued persistence of PEDV on commercial swine farms. Our findings provide important insight into regional PEDV strains in circulation, which may assist future inclusions of suitable strains for future PEDV vaccines.",2019 Apr 30,"['Tuanthap, Supansa', 'Vongpunsawad, Sompong', 'Phupolphan, Cherdpong', 'Duang-in, Ausanee', 'Wattanaphansak, Suphot', 'Assavacheep, Pornchalit', 'Theamboonlers, Apiradee', 'Luengyosluechakul, Supol', 'Amonsin, Alongkorn', 'Poovorawan, Yong']",PeerJ,,,True
a27adabfa89d32df634f7e7a9a6056b36ded5031,PMC,"Human, Nonhuman Primate, and Bat Cells Are Broadly Susceptible to Tibrovirus Particle Cell Entry",http://dx.doi.org/10.3389/fmicb.2019.00856,PMC6499107,31105663,CC BY,"In 2012, the genome of a novel rhabdovirus, Bas-Congo virus (BASV), was discovered in the acute-phase serum of a Congolese patient with presumed viral hemorrhagic fever. In the absence of a replicating virus isolate, fulfilling Koch’s postulates to determine whether BASV is indeed a human virus and/or pathogen has been impossible. However, experiments with vesiculoviral particles pseudotyped with Bas-Congo glycoprotein suggested that BASV particles can enter cells from multiple animals, including humans. In 2015, genomes of two related viruses, Ekpoma virus 1 (EKV-1) and Ekpoma virus 2 (EKV-2), were detected in human sera in Nigeria. Isolates could not be obtained. Phylogenetic analyses led to the classification of BASV, EKV-1, and EKV-2 in the same genus, Tibrovirus, together with five biting midge-borne rhabdoviruses [i.e., Beatrice Hill virus (BHV), Bivens Arm virus (BAV), Coastal Plains virus (CPV), Sweetwater Branch virus (SWBV), and Tibrogargan virus (TIBV)] not known to infect humans. Using individual recombinant vesiculoviruses expressing the glycoproteins of all eight known tibroviruses and more than 75 cell lines representing different animal species, we demonstrate that the glycoproteins of all tibroviruses can mediate vesiculovirus particle entry into human, bat, nonhuman primate, cotton rat, boa constrictor, and Asian tiger mosquito cells. Using four of five isolated authentic tibroviruses (i.e., BAV, CPV, SWBV, and TIBV), our experiments indicate that many cell types may be partially resistant to tibrovirus replication after virion cell entry. Consequently, experimental data solely obtained from experiments using tibrovirus surrogate systems (e.g., vesiculoviral pseudotypes, recombinant vesiculoviruses) cannot be used to predict whether BASV, or any other tibrovirus, infects humans.",2019 Apr 26,"['Caì, Yíngyún', 'Yú, Shuǐqìng', 'Jangra, Rohit K.', 'Postnikova, Elena N.', 'Wada, Jiro', 'Tesh, Robert B.', 'Whelan, Sean P. J.', 'Lauck, Michael', 'Wiley, Michael R.', 'Finch, Courtney L.', 'Radoshitzky, Sheli R.', 'O’Connor, David H.', 'Palacios, Gustavo', 'Chandran, Kartik', 'Chiu, Charles Y.', 'Kuhn, Jens H.']",Front Microbiol,,,True
20ae5549ea5761744ffac3015a31a03816699a49,PMC,PD-1 Dynamically Regulates Inflammation and Development of Brain-Resident Memory CD8 T Cells During Persistent Viral Encephalitis,http://dx.doi.org/10.3389/fimmu.2019.00783,PMC6499176,31105690,CC BY,"Programmed cell death-1 (PD-1) receptor signaling dampens the functionality of T cells faced with repetitive antigenic stimulation from chronic infections or tumors. Using intracerebral (i.c.) inoculation with mouse polyomavirus (MuPyV), we have shown that CD8 T cells establish a PD-1(hi), tissue-resident memory population in the brains (bT(RM)) of mice with a low-level persistent infection. In MuPyV encephalitis, PD-L1 was expressed on infiltrating myeloid cells, microglia and astrocytes, but not on oligodendrocytes. Engagement of PD-1 on anti-MuPyV CD8 T cells limited their effector activity. NanoString gene expression analysis showed that neuroinflammation was higher in PD-L1(−/−) than wild type mice at day 8 post-infection, the peak of the MuPyV-specific CD8 response. During the persistent phase of infection, however, the absence of PD-1 signaling was found to be associated with a lower inflammatory response than in wild type mice. Genetic disruption and intracerebroventricular blockade of PD-1 signaling resulted in an increase in number of MuPyV-specific CD8 bT(RM) and the fraction of these cells expressing CD103, the αE integrin commonly used to define tissue-resident T cells. However, PD-L1(−/−) mice persistently infected with MuPyV showed impaired virus control upon i.c. re-infection with MuPyV. Collectively, these data reveal a temporal duality in PD-1-mediated regulation of MuPyV-associated neuroinflammation. PD-1 signaling limited the severity of neuroinflammation during acute infection but sustained a level of inflammation during persistent infection for maintaining control of virus re-infection.",2019 Apr 17,"['Shwetank,', 'Frost, Elizabeth L.', 'Mockus, Taryn E.', 'Ren, Heather M.', 'Toprak, Mesut', 'Lauver, Matthew D.', 'Netherby-Winslow, Colleen S.', 'Jin, Ge', 'Cosby, Jennifer M.', 'Evavold, Brian D.', 'Lukacher, Aron E.']",Front Immunol,,,True
9268d8f6495e6c459fbd82a4ffaea504fd816751,PMC,Zika virus: mapping and reprogramming the entry,http://dx.doi.org/10.1186/s12964-019-0349-z,PMC6500006,31053158,CC BY,"BACKGROUND: The flaviviridae family comprises single-stranded RNA viruses that enter cells via clathrin-mediated pH-dependent endocytosis. Although the initial events of the virus entry have been already identified, data regarding intracellular virus trafficking and delivery to the replication site are limited. The purpose of this study was to map the transport route of Zika virus and to identify the fusion site within the endosomal compartment. METHODS: Tracking of viral particles in the cell was carried out with confocal microscopy. Immunostaining of two structural proteins of Zika virus enabled precise mapping of the route of the ribonucleocapsid and the envelope and, consequently, mapping the fusion site in the endosomal compartment. The results were verified using RNAi silencing and chemical inhibitors. RESULTS: After endocytic internalization, Zika virus is trafficked through the endosomal compartment to fuse in late endosomes. Inhibition of endosome acidification using bafilomycin A1 hampers the infection, as the fusion is inhibited; instead, the virus is transported to late compartments where it undergoes proteolytic degradation. The degradation products are ejected from the cell via slow recycling vesicles. Surprisingly, NH(4)Cl, which is also believed to block endosome acidification, shows a very different mode of action. In the presence of this basic compound, the endocytic hub is reprogrammed. Zika virus-containing vesicles never reach the late stage, but are rapidly trafficked to the plasma membrane via a fast recycling pathway after the clathrin-mediated endocytosis. Further, we also noted that, similarly as other members of the flaviviridae family, Zika virus undergoes furin- or furin-like-dependent activation during late steps of infection, while serine or cysteine proteases are not required for Zika virus maturation or entry. CONCLUSIONS: Zika virus fusion occurs in late endosomes and is pH-dependent. These results broaden our understanding of Zika virus intracellular trafficking and may in future allow for development of novel treatment strategies. Further, we identified a novel mode of action for agents commonly used in studies of virus entry. Schematic representation of differences in ZIKV trafficking in the presence of Baf A1 and NH(4)Cl [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12964-019-0349-z) contains supplementary material, which is available to authorized users.",2019 May 3,"['Owczarek, Katarzyna', 'Chykunova, Yuliya', 'Jassoy, Christian', 'Maksym, Beata', 'Rajfur, Zenon', 'Pyrc, Krzysztof']",Cell Commun Signal,,,True
fe53e5ca071be4ba98a8366548192fc00d35333b,PMC,A specific sequence in the genome of respiratory syncytial virus regulates the generation of copy-back defective viral genomes,http://dx.doi.org/10.1371/journal.ppat.1007707,PMC6504078,30995283,CC BY,"Defective viral genomes of the copy-back type (cbDVGs) are the primary initiators of the antiviral immune response during infection with respiratory syncytial virus (RSV) both in vitro and in vivo. However, the mechanism governing cbDVG generation remains unknown, thereby limiting our ability to manipulate cbDVG content in order to modulate the host response to infection. Here we report a specific genomic signal that mediates the generation of a subset of RSV cbDVG species. Using a customized bioinformatics tool, we identified regions in the RSV genome frequently used to generate cbDVGs during infection. We then created a minigenome system to validate the function of one of these sequences and to determine if specific nucleotides were essential for cbDVG generation at that position. Further, we created a recombinant virus unable to produce a subset of cbDVGs due to mutations introduced in this sequence. The identified sequence was also found as a site for cbDVG generation during natural RSV infections, and common cbDVGs originated at this sequence were found among samples from various infected patients. These data demonstrate that sequences encoded in the viral genome determine the location of cbDVG formation and, therefore, the generation of cbDVGs is not a stochastic process. These findings open the possibility of genetically manipulating cbDVG formation to modulate infection outcome.",2019 Apr 17,"['Sun, Yan', 'Kim, Eun Ji', 'Felt, Sébastien A.', 'Taylor, Louis J.', 'Agarwal, Divyansh', 'Grant, Gregory R.', 'López, Carolina B.']",PLoS Pathog,,,True
68c13cb464cbe2b35102008464c5c196f7c122c1,PMC,Determinants of QTL Mapping Power in the Realized Collaborative Cross,http://dx.doi.org/10.1534/g3.119.400194,PMC6505132,30914424,CC BY,"The Collaborative Cross (CC) is a mouse genetic reference population whose range of applications includes quantitative trait loci (QTL) mapping. The design of a CC QTL mapping study involves multiple decisions, including which and how many strains to use, and how many replicates per strain to phenotype, all viewed within the context of hypothesized QTL architecture. Until now, these decisions have been informed largely by early power analyses that were based on simulated, hypothetical CC genomes. Now that more than 50 CC strains are available and more than 70 CC genomes have been observed, it is possible to characterize power based on realized CC genomes. We report power analyses from extensive simulations and examine several key considerations: 1) the number of strains and biological replicates, 2) the QTL effect size, 3) the presence of population structure, and 4) the distribution of functionally distinct alleles among the founder strains at the QTL. We also provide general power estimates to aide in the design of future experiments. All analyses were conducted with our R package, SPARCC (Simulated Power Analysis in the Realized Collaborative Cross), developed for performing either large scale power analyses or those tailored to particular CC experiments.",2019 May 1,"['Keele, Gregory R.', 'Crouse, Wesley L.', 'Kelada, Samir N. P.', 'Valdar, William']",G3 (Bethesda),,,True
3060dac173270e62020e18ce6fcdcb4b8bf4fd8d,PMC,Whole Genome Sequencing and Progress Toward Full Inbreeding of the Mouse Collaborative Cross Population,http://dx.doi.org/10.1534/g3.119.400039,PMC6505143,30858237,CC BY,"Two key features of recombinant inbred panels are well-characterized genomes and reproducibility. Here we report on the sequenced genomes of six additional Collaborative Cross (CC) strains and on inbreeding progress of 72 CC strains. We have previously reported on the sequences of 69 CC strains that were publicly available, bringing the total of CC strains with whole genome sequence up to 75. The sequencing of these six CC strains updates the efforts toward inbreeding undertaken by the UNC Systems Genetics Core. The timing reflects our competing mandates to release to the public as many CC strains as possible while achieving an acceptable level of inbreeding. The new six strains have a higher than average founder contribution from non-domesticus strains than the previously released CC strains. Five of the six strains also have high residual heterozygosity (>14%), which may be related to non-domesticus founder contributions. Finally, we report on updated estimates on residual heterozygosity across the entire CC population using a novel, simple and cost effective genotyping platform on three mice from each strain. We observe a reduction in residual heterozygosity across all previously released CC strains. We discuss the optimal use of different genetic resources available for the CC population.",2019 Mar 11,"['Shorter, John R.', 'Najarian, Maya L.', 'Bell, Timothy A.', 'Blanchard, Matthew', 'Ferris, Martin T.', 'Hock, Pablo', 'Kashfeen, Anwica', 'Kirchoff, Kathryn E.', 'Linnertz, Colton L.', 'Sigmon, J. Sebastian', 'Miller, Darla R.', 'McMillan, Leonard', 'Pardo-Manuel de Villena, Fernando']",G3 (Bethesda),,,True
fdf021cfe745daed338cce7eaa5e548581477ff4,PMC,A Diallel of the Mouse Collaborative Cross Founders Reveals Strong Strain-Specific Maternal Effects on Litter Size,http://dx.doi.org/10.1534/g3.118.200847,PMC6505174,30877080,CC BY,"Reproductive success in the eight founder strains of the Collaborative Cross (CC) was measured using a diallel-mating scheme. Over a 48-month period we generated 4,448 litters, and provided 24,782 weaned pups for use in 16 different published experiments. We identified factors that affect the average litter size in a cross by estimating the overall contribution of parent-of-origin, heterosis, inbred, and epistatic effects using a Bayesian zero-truncated overdispersed Poisson mixed model. The phenotypic variance of litter size has a substantial contribution (82%) from unexplained and environmental sources, but no detectable effect of seasonality. Most of the explained variance was due to additive effects (9.2%) and parental sex (maternal vs. paternal strain; 5.8%), with epistasis accounting for 3.4%. Within the parental effects, the effect of the dam’s strain explained more than the sire’s strain (13.2% vs. 1.8%), and the dam’s strain effects account for 74.2% of total variation explained. Dams from strains C57BL/6J and NOD/ShiLtJ increased the expected litter size by a mean of 1.66 and 1.79 pups, whereas dams from strains WSB/EiJ, PWK/PhJ, and CAST/EiJ reduced expected litter size by a mean of 1.51, 0.81, and 0.90 pups. Finally, there was no strong evidence for strain-specific effects on sex ratio distortion. Overall, these results demonstrate that strains vary substantially in their reproductive ability depending on their genetic background, and that litter size is largely determined by dam’s strain rather than sire’s strain effects, as expected. This analysis adds to our understanding of factors that influence litter size in mammals, and also helps to explain breeding successes and failures in the extinct lines and surviving CC strains.",2019 Mar 15,"['Shorter, John R.', 'Maurizio, Paul L.', 'Bell, Timothy A.', 'Shaw, Ginger D.', 'Miller, Darla R.', 'Gooch, Terry J.', 'Spence, Jason S.', 'McMillan, Leonard', 'Valdar, William', 'Pardo-Manuel de Villena, Fernando']",G3 (Bethesda),,,True
efd94d1135c5ee11c2af624b344881e079a5ce7a,PMC,‘Tiny Iceland’ preparing for Ebola in a globalized world,http://dx.doi.org/10.1080/16549716.2019.1597451,PMC6507955,31062663,CC BY,"Background: The Ebola epidemic in West Africa caused global fear and stirred up worldwide preparedness activities in countries sharing borders with those affected, and in geographically far-away countries such as Iceland. Objective: To describe and analyse Ebola preparedness activities within the Icelandic healthcare system, and to explore the perspectives and experiences of managers and frontline health workers. Methods: A qualitative case study, based on semi-structured interviews with 21 staff members in the national Ebola Treatment Team, Emergency Room at Landspitali University Hospital, and managers of the response team. Results: Contextual factors such as culture and demography influenced preparedness, and contributed to the positive state of mind of participants, and ingenuity in using available resources for preparedness. While participants believed they were ready to take on the task of Ebola, they also had doubts about the chances of Ebola ever reaching Iceland. Yet, factors such as fear of Ebola and the perceived stigma associated with caring for a potentially infected Ebola patient, influenced the preparation process and resulted in plans for specific precautions by staff to secure the safety of their families. There were also concerns about the teamwork and lack of commitment by some during training. Being a ‘tiny’ nation was seen as both an asset and a weakness in the preparation process. Honest information sharing and scenario-based training contributed to increased confidence amongst participants in the response plans. Conclusions: Communication and training were important for preparedness of health staff in Iceland, in order to receive, admit, and treat a patient suspected of having Ebola, while doubts prevailed on staff capacity to properly do so. For optimal preparedness, likely scenarios for future global security health threats need to be repeatedly enacted, and areas plagued by poverty and fragile healthcare systems require global support.",2019 May 7,"['Gunnlaugsson, Geir', 'Hauksdóttir, Íris Eva', 'Bygbjerg, Ib Christian', 'Pinkowski Tersbøl, Britt']",Glob Health Action,,,True
4dbe45a5961f17aaa90175a28dfec6fe5ab9094d,PMC,Go go gadget glycoprotein!: HSV-1 draws on its sizeable glycoprotein tool kit to customize its diverse entry routes,http://dx.doi.org/10.1371/journal.ppat.1007660,PMC6508585,31071197,CC BY,,2019 May 9,"['Hilterbrand, Adam T.', 'Heldwein, Ekaterina E.']",PLoS Pathog,,,True
135f5ee5fba1a4280521d45e4fa882354f63e691,PMC,Epidemic curves made easy using the R package incidence,http://dx.doi.org/10.12688/f1000research.18002.1,PMC6509961,31119031,CC BY,"The epidemiological curve (epicurve) is one of the simplest yet most useful tools used by field epidemiologists, modellers, and decision makers for assessing the dynamics of infectious disease epidemics. Here, we present the free, open-source package incidence for the R programming language, which allows users to easily compute, handle, and visualise epicurves from unaggregated linelist data. This package was built in accordance with the development guidelines of the R Epidemics Consortium (RECON), which aim to ensure robustness and reliability through extensive automated testing, documentation, and good coding practices. As such, it fills an important gap in the toolbox for outbreak analytics using the R software, and provides a solid building block for further developments in infectious disease modelling. incidence is available from https://www.repidemicsconsortium.org/incidence.",2019 Jan 31,"['Kamvar, Zhian N.', 'Cai, Jun', 'Pulliam, Juliet R.C.', 'Schumacher, Jakob', 'Jombart, Thibaut']",F1000Res,,,True
02a009e42054081b441d0f4b203679c4b0cae38d,PMC,Three asymptomatic animal infection models of hemorrhagic fever with renal syndrome caused by hantaviruses,http://dx.doi.org/10.1371/journal.pone.0216700,PMC6510444,31075144,CC0,"Hantaan virus (HTNV) and Puumala virus (PUUV) are rodent-borne hantaviruses that are the primary causes of hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia. The development of well characterized animal models of HTNV and PUUV infection is critical for the evaluation and the potential licensure of HFRS vaccines and therapeutics. In this study we present three animal models of HTNV infection (hamster, ferret and marmoset), and two animal models of PUUV infection (hamster, ferret). Infection of hamsters with a ~3 times the infectious dose 99% (ID(99)) of HTNV by the intramuscular and ~1 ID(99) of HTNV by the intranasal route leads to a persistent asymptomatic infection, characterized by sporadic viremia and high levels of viral genome in the lung, brain and kidney. In contrast, infection of hamsters with ~2 ID(99) of PUUV by the intramuscular or ~1 ID(99) of PUUV by the intranasal route leads to seroconversion with no detectable viremia, and a transient detection of viral genome. Infection of ferrets with a high dose of either HTNV or PUUV by the intramuscular route leads to seroconversion and gradual weight loss, though kidney function remained unimpaired and serum viremia and viral dissemination to organs was not detected. In marmosets a 1,000 PFU HTNV intramuscular challenge led to robust seroconversion and neutralizing antibody production. Similarly to the ferret model of HTNV infection, no renal impairment, serum viremia or viral dissemination to organs was detected in marmosets. This is the first report of hantavirus infection in ferrets and marmosets.",2019 May 10,"['Perley, Casey C.', 'Brocato, Rebecca L.', 'Kwilas, Steven A.', 'Daye, Sharon', 'Moreau, Alicia', 'Nichols, Donald K.', 'Wetzel, Kelly S.', 'Shamblin, Joshua', 'Hooper, Jay W.']",PLoS One,,,True
82114e8ec9b0ac800be54578d1fd23d945209f12,PMC,"Molecular characterization of two novel reoviruses isolated from Muscovy ducklings in Guangdong, China",http://dx.doi.org/10.1186/s12917-019-1877-x,PMC6511161,31077188,CC BY,"BACKGROUND: Novel Muscovy duck reovirus (N-MDRV), emerged in southeast China in 2002, which can infect a wide range of waterfowl and induces clinical signs and cytopathic effects that are distinct from those of classical MDRV, and continues to cause high morbidity and 5–50% mortality in ducklings. The present study aimed to investigate the characteristics of two novel reoviruses isolated from Muscovy ducklings in Guangdong, China. RESULTS: Two novel MDRV strains, designated as MDRV-SH12 and MDRV-DH13, were isolated from two diseased Muscovy ducklings in Guangdong province, China in June 2012 and September 2013, respectively. Sequencing of the complete genomes of these two viruses showed that they consisted of 23,418 bp and were divided into 10 segments, ranging from 1191 bp (S4) to 3959 bp (L1) in length, and all segments contained conserved sequences in the 5′ non-coding region (GCUUUU) and 3′ non-coding region (UCAUC). Pairwise sequence comparisons demonstrated that MDRV-SH12 and MDRV-DH13 showed the highest similarity with novel MDRVs. Phylogenetic analyses of the nucleotide sequences of all 10 segments revealed that MDRV-SH12 and MDRV-DH13 were clustered together with other novel waterfowl-origin reoviruses and were distinct from classical waterfowl-origin and chicken-origin reoviruses. The analyses also showed possible genetic re-assortment events in segment M2 between waterfowl-origin and chicken-origin reoviruses and the segments encoding λA, μA, μNS, σA, and σNS between classical and novel waterfowl-origin reoviruses. Potential recombination events detection in segment S2 suggests that MDRV-SH12 and MDRV-DH13 may be recombinants of classical and novel WRVs. CONCLUSIONS: The results presented in this study, the full genomic data for two novel MDRV strains, will improve our understanding of the evolutionary relationships among the waterfowl-origin reoviruses circulating in China, and may aid in the development of more effective vaccines against various waterfowl-origin reoviruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-019-1877-x) contains supplementary material, which is available to authorized users.",2019 May 10,"['Zhang, Xue-Lian', 'Shao, Jian-Wei', 'Li, Xiao-Wen', 'Mei, Min-Min', 'Guo, Jin-Yue', 'Li, Wen-Feng', 'Huang, Wen-Jing', 'Chi, Shi-Hong', 'Yuan, Sheng', 'Li, Zhi-Li', 'Huang, Shu-Jian']",BMC Vet Res,,,True
ce2f322118541b9901f218ce6e49177e5d25dd6c,PMC,Simultaneous detection and differentiation of canine parvovirus and feline parvovirus by high resolution melting analysis,http://dx.doi.org/10.1186/s12917-019-1898-5,PMC6511188,31077252,CC BY,"BACKGROUND: Canine parvovirus (CPV) and feline parvovirus (FPV) are causative agents of diarrhea in dogs and cats, which manifests as depression, vomiting, fever, loss of appetite, leucopenia, and diarrhea in young animals. CPV and FPV can single or mixed infect cats and cause disease. To diagnose sick animals effectively, an effective virus diagnostic and genome typing method with high sensitivity and specificity is required. RESULTS: In this study, a conserved segment containing one SNP A4408C of parvovirus was used for real-time PCR amplification. Subsequently, data were auto-analyzed and plotted using Applied Biosystems® High Resolution Melt Software v3.1. Results showed that CPV and FPV can be detected simultaneously in a single PCR reaction. No cross-reactions were observed with canine adenovirus, canine coronavirus, and canine distemper virus. The assay had a detection limit of 4.2 genome copies of CPV and FPV. A total of 80 clinical samples were subjected to this assay, as well as to conventional PCR-sequence assay and virus isolation. Results showed that the percentage of agreement of the assay and other methods are high. CONCLUSIONS: In short, we have developed a diagnostic test for the accurate detection and differentiation of CPV and FPV in fecal samples, which is also cost effective.",2019 May 10,"['Sun, Yaru', 'Cheng, Yuening', 'Lin, Peng', 'Zhang, Hewei', 'Yi, Li', 'Tong, Mingwei', 'Cao, Zhigang', 'Li, Shuang', 'Cheng, Shipeng', 'Wang, Jianke']",BMC Vet Res,,,True
0cd1453fb9f28809b7544dcdcb0d6b3b4e42b3cc,PMC,Viral Regulation of RNA Granules in Infected Cells,http://dx.doi.org/10.1007/s12250-019-00122-3,PMC6513825,31037644,CC BY,"RNA granules are cytoplasmic, microscopically visible, non-membrane ribo-nucleoprotein structures and are important posttranscriptional regulators in gene expression by controlling RNA translation and stability. TIA/G3BP/PABP-specific stress granules (SG) and GW182/DCP-specific RNA processing bodies (PB) are two major distinguishable RNA granules in somatic cells and contain various ribosomal subunits, translation factors, scaffold proteins, RNA-binding proteins, RNA decay enzymes and helicases to exclude mRNAs from the cellular active translational pool. Although SG formation is inducible due to cellular stress, PB exist physiologically in every cell. Both RNA granules are important components of the host antiviral defense. Virus infection imposes stress on host cells and thus induces SG formation. However, both RNA and DNA viruses must confront the hostile environment of host innate immunity and apply various strategies to block the formation of SG and PB for their effective infection and multiplication. This review summarizes the current research development in the field and the mechanisms of how individual viruses suppress the formation of host SG and PB for virus production.",2019 Apr 29,"['Zhang, Qiang', 'Sharma, Nishi R.', 'Zheng, Zhi-Ming', 'Chen, Mingzhou']",Virol Sin,,,True
1df0f9012de37de02b7af4bd23931f626c7bbc71,PMC,Impact of Host Genetics and Biological Response Modifiers on Respiratory Tract Infections,http://dx.doi.org/10.3389/fimmu.2019.01013,PMC6513887,31134083,CC BY,"Host susceptibility to respiratory tract infections (RTI) is dependent on both genetic and acquired risk factors. Repeated bacterial and viral RTI, such as pneumonia from encapsulated microorganisms, respiratory tract infections related to respiratory syncytial virus or influenza, and even the development of bronchiectasis and asthma, are often reported as the first symptom of primary immunodeficiencies. In the same way, neutropenia is a well-known risk factor for invasive aspergillosis, as well as lymphopenia for Pneumocystis, and mycobacterial infections. However, in the last decades a better knowledge of immune signaling networks and the introduction of next generation sequencing have increased the number and diversity of known inborn errors of immunity. On the other hand, the use of monoclonal antibodies targeting cytokines, such as tumor necrosis factor alpha has revealed new risk groups for infections, such as tuberculosis. The use of biological response modifiers has spread to almost all medical specialties, including inflammatory diseases and neoplasia, and are being used to target different signaling networks that may mirror some of the known immune deficiencies. From a clinical perspective, the individual contribution of genetics, and/or targeted treatments, to immune dysregulation is difficult to assess. The aim of this article is to review the known and newly described mechanisms of impaired immune signaling that predispose to RTI, including new insights into host genetics and the impact of biological response modifiers, and to summarize clinical recommendations regarding vaccines and prophylactic treatments in order to prevent infections.",2019 May 7,"['Lacoma, Alicia', 'Mateo, Lourdes', 'Blanco, Ignacio', 'Méndez, Maria J.', 'Rodrigo, Carlos', 'Latorre, Irene', 'Villar-Hernandez, Raquel', 'Domínguez, Jose', 'Prat, Cristina']",Front Immunol,,,True
55b7a3bbfc2bc9da840ece3807497a56f253a3d5,PMC,Microglial cell loss after ischemic stroke favors brain neutrophil accumulation,http://dx.doi.org/10.1007/s00401-018-1954-4,PMC6513908,30580383,CC BY,"Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood–brain barrier and exacerbate the lesion. However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated. Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow. Based on previous observations of microglia phagocytosing neutrophils recruited to the ischemic brain lesion, we hypothesized that microglial cells might control neutrophil accumulation in the injured brain. We studied a model of permanent occlusion of the middle cerebral artery in mice, including microglia- and neutrophil-reporter mice. Using various in vitro and in vivo strategies to impair microglial function or to eliminate microglia by targeting colony stimulating factor 1 receptor (CSF1R), this study demonstrates that microglial phagocytosis of neutrophils has fundamental consequences for the ischemic tissue. We found that reactive microglia engulf neutrophils at the periphery of the ischemic lesion, whereas local microglial cell loss and dystrophy occurring in the ischemic core are associated with the accumulation of neutrophils first in perivascular spaces and later in the parenchyma. Accordingly, microglia depletion by long-term treatment with a CSF1R inhibitor increased the numbers of neutrophils and enlarged the ischemic lesion. Hence, microglial phagocytic function sets a critical line of defense against the vascular and tissue damaging capacity of neutrophils in brain ischemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1954-4) contains supplementary material, which is available to authorized users.",2019 Dec 22,"['Otxoa-de-Amezaga, Amaia', 'Miró-Mur, Francesc', 'Pedragosa, Jordi', 'Gallizioli, Mattia', 'Justicia, Carles', 'Gaja-Capdevila, Núria', 'Ruíz-Jaen, Francisca', 'Salas-Perdomo, Angélica', 'Bosch, Anna', 'Calvo, Maria', 'Márquez-Kisinousky, Leonardo', 'Denes, Adam', 'Gunzer, Matthias', 'Planas, Anna M.']",Acta Neuropathol,,,False
43ac151f826183e1b85394362fa08b4ba62ab389,PMC,Microglial cell loss after ischemic stroke favors brain neutrophil accumulation,http://dx.doi.org/10.1007/s00401-018-1954-4,PMC6513908,30580383,CC BY,"Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood–brain barrier and exacerbate the lesion. However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated. Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow. Based on previous observations of microglia phagocytosing neutrophils recruited to the ischemic brain lesion, we hypothesized that microglial cells might control neutrophil accumulation in the injured brain. We studied a model of permanent occlusion of the middle cerebral artery in mice, including microglia- and neutrophil-reporter mice. Using various in vitro and in vivo strategies to impair microglial function or to eliminate microglia by targeting colony stimulating factor 1 receptor (CSF1R), this study demonstrates that microglial phagocytosis of neutrophils has fundamental consequences for the ischemic tissue. We found that reactive microglia engulf neutrophils at the periphery of the ischemic lesion, whereas local microglial cell loss and dystrophy occurring in the ischemic core are associated with the accumulation of neutrophils first in perivascular spaces and later in the parenchyma. Accordingly, microglia depletion by long-term treatment with a CSF1R inhibitor increased the numbers of neutrophils and enlarged the ischemic lesion. Hence, microglial phagocytic function sets a critical line of defense against the vascular and tissue damaging capacity of neutrophils in brain ischemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1954-4) contains supplementary material, which is available to authorized users.",2019 Dec 22,"['Otxoa-de-Amezaga, Amaia', 'Miró-Mur, Francesc', 'Pedragosa, Jordi', 'Gallizioli, Mattia', 'Justicia, Carles', 'Gaja-Capdevila, Núria', 'Ruíz-Jaen, Francisca', 'Salas-Perdomo, Angélica', 'Bosch, Anna', 'Calvo, Maria', 'Márquez-Kisinousky, Leonardo', 'Denes, Adam', 'Gunzer, Matthias', 'Planas, Anna M.']",Acta Neuropathol,,,False
fa23be737ae80eccc6f4ab5a407fadea3b22ca2e,PMC,Microglial cell loss after ischemic stroke favors brain neutrophil accumulation,http://dx.doi.org/10.1007/s00401-018-1954-4,PMC6513908,30580383,CC BY,"Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood–brain barrier and exacerbate the lesion. However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated. Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow. Based on previous observations of microglia phagocytosing neutrophils recruited to the ischemic brain lesion, we hypothesized that microglial cells might control neutrophil accumulation in the injured brain. We studied a model of permanent occlusion of the middle cerebral artery in mice, including microglia- and neutrophil-reporter mice. Using various in vitro and in vivo strategies to impair microglial function or to eliminate microglia by targeting colony stimulating factor 1 receptor (CSF1R), this study demonstrates that microglial phagocytosis of neutrophils has fundamental consequences for the ischemic tissue. We found that reactive microglia engulf neutrophils at the periphery of the ischemic lesion, whereas local microglial cell loss and dystrophy occurring in the ischemic core are associated with the accumulation of neutrophils first in perivascular spaces and later in the parenchyma. Accordingly, microglia depletion by long-term treatment with a CSF1R inhibitor increased the numbers of neutrophils and enlarged the ischemic lesion. Hence, microglial phagocytic function sets a critical line of defense against the vascular and tissue damaging capacity of neutrophils in brain ischemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1954-4) contains supplementary material, which is available to authorized users.",2019 Dec 22,"['Otxoa-de-Amezaga, Amaia', 'Miró-Mur, Francesc', 'Pedragosa, Jordi', 'Gallizioli, Mattia', 'Justicia, Carles', 'Gaja-Capdevila, Núria', 'Ruíz-Jaen, Francisca', 'Salas-Perdomo, Angélica', 'Bosch, Anna', 'Calvo, Maria', 'Márquez-Kisinousky, Leonardo', 'Denes, Adam', 'Gunzer, Matthias', 'Planas, Anna M.']",Acta Neuropathol,,,False
fc91907feb62751c4fec0256cba86bb0a2e09828,PMC,Microglial cell loss after ischemic stroke favors brain neutrophil accumulation,http://dx.doi.org/10.1007/s00401-018-1954-4,PMC6513908,30580383,CC BY,"Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood–brain barrier and exacerbate the lesion. However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated. Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow. Based on previous observations of microglia phagocytosing neutrophils recruited to the ischemic brain lesion, we hypothesized that microglial cells might control neutrophil accumulation in the injured brain. We studied a model of permanent occlusion of the middle cerebral artery in mice, including microglia- and neutrophil-reporter mice. Using various in vitro and in vivo strategies to impair microglial function or to eliminate microglia by targeting colony stimulating factor 1 receptor (CSF1R), this study demonstrates that microglial phagocytosis of neutrophils has fundamental consequences for the ischemic tissue. We found that reactive microglia engulf neutrophils at the periphery of the ischemic lesion, whereas local microglial cell loss and dystrophy occurring in the ischemic core are associated with the accumulation of neutrophils first in perivascular spaces and later in the parenchyma. Accordingly, microglia depletion by long-term treatment with a CSF1R inhibitor increased the numbers of neutrophils and enlarged the ischemic lesion. Hence, microglial phagocytic function sets a critical line of defense against the vascular and tissue damaging capacity of neutrophils in brain ischemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1954-4) contains supplementary material, which is available to authorized users.",2019 Dec 22,"['Otxoa-de-Amezaga, Amaia', 'Miró-Mur, Francesc', 'Pedragosa, Jordi', 'Gallizioli, Mattia', 'Justicia, Carles', 'Gaja-Capdevila, Núria', 'Ruíz-Jaen, Francisca', 'Salas-Perdomo, Angélica', 'Bosch, Anna', 'Calvo, Maria', 'Márquez-Kisinousky, Leonardo', 'Denes, Adam', 'Gunzer, Matthias', 'Planas, Anna M.']",Acta Neuropathol,,,False
4d9c32e08a92be405f822610865e26a79e391db8,PMC,Microglial cell loss after ischemic stroke favors brain neutrophil accumulation,http://dx.doi.org/10.1007/s00401-018-1954-4,PMC6513908,30580383,CC BY,"Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood–brain barrier and exacerbate the lesion. However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated. Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow. Based on previous observations of microglia phagocytosing neutrophils recruited to the ischemic brain lesion, we hypothesized that microglial cells might control neutrophil accumulation in the injured brain. We studied a model of permanent occlusion of the middle cerebral artery in mice, including microglia- and neutrophil-reporter mice. Using various in vitro and in vivo strategies to impair microglial function or to eliminate microglia by targeting colony stimulating factor 1 receptor (CSF1R), this study demonstrates that microglial phagocytosis of neutrophils has fundamental consequences for the ischemic tissue. We found that reactive microglia engulf neutrophils at the periphery of the ischemic lesion, whereas local microglial cell loss and dystrophy occurring in the ischemic core are associated with the accumulation of neutrophils first in perivascular spaces and later in the parenchyma. Accordingly, microglia depletion by long-term treatment with a CSF1R inhibitor increased the numbers of neutrophils and enlarged the ischemic lesion. Hence, microglial phagocytic function sets a critical line of defense against the vascular and tissue damaging capacity of neutrophils in brain ischemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1954-4) contains supplementary material, which is available to authorized users.",2019 Dec 22,"['Otxoa-de-Amezaga, Amaia', 'Miró-Mur, Francesc', 'Pedragosa, Jordi', 'Gallizioli, Mattia', 'Justicia, Carles', 'Gaja-Capdevila, Núria', 'Ruíz-Jaen, Francisca', 'Salas-Perdomo, Angélica', 'Bosch, Anna', 'Calvo, Maria', 'Márquez-Kisinousky, Leonardo', 'Denes, Adam', 'Gunzer, Matthias', 'Planas, Anna M.']",Acta Neuropathol,,,False
326b0cf739b6633ed4a6d857ea463548835caf7c,PMC,Microglial cell loss after ischemic stroke favors brain neutrophil accumulation,http://dx.doi.org/10.1007/s00401-018-1954-4,PMC6513908,30580383,CC BY,"Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood–brain barrier and exacerbate the lesion. However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated. Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow. Based on previous observations of microglia phagocytosing neutrophils recruited to the ischemic brain lesion, we hypothesized that microglial cells might control neutrophil accumulation in the injured brain. We studied a model of permanent occlusion of the middle cerebral artery in mice, including microglia- and neutrophil-reporter mice. Using various in vitro and in vivo strategies to impair microglial function or to eliminate microglia by targeting colony stimulating factor 1 receptor (CSF1R), this study demonstrates that microglial phagocytosis of neutrophils has fundamental consequences for the ischemic tissue. We found that reactive microglia engulf neutrophils at the periphery of the ischemic lesion, whereas local microglial cell loss and dystrophy occurring in the ischemic core are associated with the accumulation of neutrophils first in perivascular spaces and later in the parenchyma. Accordingly, microglia depletion by long-term treatment with a CSF1R inhibitor increased the numbers of neutrophils and enlarged the ischemic lesion. Hence, microglial phagocytic function sets a critical line of defense against the vascular and tissue damaging capacity of neutrophils in brain ischemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1954-4) contains supplementary material, which is available to authorized users.",2019 Dec 22,"['Otxoa-de-Amezaga, Amaia', 'Miró-Mur, Francesc', 'Pedragosa, Jordi', 'Gallizioli, Mattia', 'Justicia, Carles', 'Gaja-Capdevila, Núria', 'Ruíz-Jaen, Francisca', 'Salas-Perdomo, Angélica', 'Bosch, Anna', 'Calvo, Maria', 'Márquez-Kisinousky, Leonardo', 'Denes, Adam', 'Gunzer, Matthias', 'Planas, Anna M.']",Acta Neuropathol,,,False
0167e22452058eec61fac1bd923dcfda6e1a15e9,PMC,Microglial cell loss after ischemic stroke favors brain neutrophil accumulation,http://dx.doi.org/10.1007/s00401-018-1954-4,PMC6513908,30580383,CC BY,"Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood–brain barrier and exacerbate the lesion. However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated. Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow. Based on previous observations of microglia phagocytosing neutrophils recruited to the ischemic brain lesion, we hypothesized that microglial cells might control neutrophil accumulation in the injured brain. We studied a model of permanent occlusion of the middle cerebral artery in mice, including microglia- and neutrophil-reporter mice. Using various in vitro and in vivo strategies to impair microglial function or to eliminate microglia by targeting colony stimulating factor 1 receptor (CSF1R), this study demonstrates that microglial phagocytosis of neutrophils has fundamental consequences for the ischemic tissue. We found that reactive microglia engulf neutrophils at the periphery of the ischemic lesion, whereas local microglial cell loss and dystrophy occurring in the ischemic core are associated with the accumulation of neutrophils first in perivascular spaces and later in the parenchyma. Accordingly, microglia depletion by long-term treatment with a CSF1R inhibitor increased the numbers of neutrophils and enlarged the ischemic lesion. Hence, microglial phagocytic function sets a critical line of defense against the vascular and tissue damaging capacity of neutrophils in brain ischemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1954-4) contains supplementary material, which is available to authorized users.",2019 Dec 22,"['Otxoa-de-Amezaga, Amaia', 'Miró-Mur, Francesc', 'Pedragosa, Jordi', 'Gallizioli, Mattia', 'Justicia, Carles', 'Gaja-Capdevila, Núria', 'Ruíz-Jaen, Francisca', 'Salas-Perdomo, Angélica', 'Bosch, Anna', 'Calvo, Maria', 'Márquez-Kisinousky, Leonardo', 'Denes, Adam', 'Gunzer, Matthias', 'Planas, Anna M.']",Acta Neuropathol,,,False
36456e621e444cfe18db5972a9669aa8712d1649,PMC,Microglial cell loss after ischemic stroke favors brain neutrophil accumulation,http://dx.doi.org/10.1007/s00401-018-1954-4,PMC6513908,30580383,CC BY,"Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood–brain barrier and exacerbate the lesion. However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated. Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow. Based on previous observations of microglia phagocytosing neutrophils recruited to the ischemic brain lesion, we hypothesized that microglial cells might control neutrophil accumulation in the injured brain. We studied a model of permanent occlusion of the middle cerebral artery in mice, including microglia- and neutrophil-reporter mice. Using various in vitro and in vivo strategies to impair microglial function or to eliminate microglia by targeting colony stimulating factor 1 receptor (CSF1R), this study demonstrates that microglial phagocytosis of neutrophils has fundamental consequences for the ischemic tissue. We found that reactive microglia engulf neutrophils at the periphery of the ischemic lesion, whereas local microglial cell loss and dystrophy occurring in the ischemic core are associated with the accumulation of neutrophils first in perivascular spaces and later in the parenchyma. Accordingly, microglia depletion by long-term treatment with a CSF1R inhibitor increased the numbers of neutrophils and enlarged the ischemic lesion. Hence, microglial phagocytic function sets a critical line of defense against the vascular and tissue damaging capacity of neutrophils in brain ischemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1954-4) contains supplementary material, which is available to authorized users.",2019 Dec 22,"['Otxoa-de-Amezaga, Amaia', 'Miró-Mur, Francesc', 'Pedragosa, Jordi', 'Gallizioli, Mattia', 'Justicia, Carles', 'Gaja-Capdevila, Núria', 'Ruíz-Jaen, Francisca', 'Salas-Perdomo, Angélica', 'Bosch, Anna', 'Calvo, Maria', 'Márquez-Kisinousky, Leonardo', 'Denes, Adam', 'Gunzer, Matthias', 'Planas, Anna M.']",Acta Neuropathol,,,False
3216a0e9b666aeaed6d219c1cc55a976e5eba55c,PMC,Microglial cell loss after ischemic stroke favors brain neutrophil accumulation,http://dx.doi.org/10.1007/s00401-018-1954-4,PMC6513908,30580383,CC BY,"Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood–brain barrier and exacerbate the lesion. However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated. Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow. Based on previous observations of microglia phagocytosing neutrophils recruited to the ischemic brain lesion, we hypothesized that microglial cells might control neutrophil accumulation in the injured brain. We studied a model of permanent occlusion of the middle cerebral artery in mice, including microglia- and neutrophil-reporter mice. Using various in vitro and in vivo strategies to impair microglial function or to eliminate microglia by targeting colony stimulating factor 1 receptor (CSF1R), this study demonstrates that microglial phagocytosis of neutrophils has fundamental consequences for the ischemic tissue. We found that reactive microglia engulf neutrophils at the periphery of the ischemic lesion, whereas local microglial cell loss and dystrophy occurring in the ischemic core are associated with the accumulation of neutrophils first in perivascular spaces and later in the parenchyma. Accordingly, microglia depletion by long-term treatment with a CSF1R inhibitor increased the numbers of neutrophils and enlarged the ischemic lesion. Hence, microglial phagocytic function sets a critical line of defense against the vascular and tissue damaging capacity of neutrophils in brain ischemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1954-4) contains supplementary material, which is available to authorized users.",2019 Dec 22,"['Otxoa-de-Amezaga, Amaia', 'Miró-Mur, Francesc', 'Pedragosa, Jordi', 'Gallizioli, Mattia', 'Justicia, Carles', 'Gaja-Capdevila, Núria', 'Ruíz-Jaen, Francisca', 'Salas-Perdomo, Angélica', 'Bosch, Anna', 'Calvo, Maria', 'Márquez-Kisinousky, Leonardo', 'Denes, Adam', 'Gunzer, Matthias', 'Planas, Anna M.']",Acta Neuropathol,,,False
dcd269e34e588ed3ce743184f98ed65229b84fdd,PMC,Microglial cell loss after ischemic stroke favors brain neutrophil accumulation,http://dx.doi.org/10.1007/s00401-018-1954-4,PMC6513908,30580383,CC BY,"Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood–brain barrier and exacerbate the lesion. However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated. Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow. Based on previous observations of microglia phagocytosing neutrophils recruited to the ischemic brain lesion, we hypothesized that microglial cells might control neutrophil accumulation in the injured brain. We studied a model of permanent occlusion of the middle cerebral artery in mice, including microglia- and neutrophil-reporter mice. Using various in vitro and in vivo strategies to impair microglial function or to eliminate microglia by targeting colony stimulating factor 1 receptor (CSF1R), this study demonstrates that microglial phagocytosis of neutrophils has fundamental consequences for the ischemic tissue. We found that reactive microglia engulf neutrophils at the periphery of the ischemic lesion, whereas local microglial cell loss and dystrophy occurring in the ischemic core are associated with the accumulation of neutrophils first in perivascular spaces and later in the parenchyma. Accordingly, microglia depletion by long-term treatment with a CSF1R inhibitor increased the numbers of neutrophils and enlarged the ischemic lesion. Hence, microglial phagocytic function sets a critical line of defense against the vascular and tissue damaging capacity of neutrophils in brain ischemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1954-4) contains supplementary material, which is available to authorized users.",2019 Dec 22,"['Otxoa-de-Amezaga, Amaia', 'Miró-Mur, Francesc', 'Pedragosa, Jordi', 'Gallizioli, Mattia', 'Justicia, Carles', 'Gaja-Capdevila, Núria', 'Ruíz-Jaen, Francisca', 'Salas-Perdomo, Angélica', 'Bosch, Anna', 'Calvo, Maria', 'Márquez-Kisinousky, Leonardo', 'Denes, Adam', 'Gunzer, Matthias', 'Planas, Anna M.']",Acta Neuropathol,,,True
2005ffa70562f5f03b57f0d19f4d63e807762964,PMC,Bovine Herpesvirus 1 Counteracts Immune Responses and Immune-Surveillance to Enhance Pathogenesis and Virus Transmission,http://dx.doi.org/10.3389/fimmu.2019.01008,PMC6514135,31134079,CC BY,"Infection of cattle by bovine herpesvirus 1 (BoHV-1) can culminate in upper respiratory tract disorders, conjunctivitis, or genital disorders. Infection also consistently leads to transient immune-suppression. BoHV-1 is the number one infectious agent in cattle that is associated with abortions in cattle. BoHV-1, as other α-herpesvirinae subfamily members, establishes latency in sensory neurons. Stressful stimuli, mimicked by the synthetic corticosteroid dexamethasone, consistently induce reactivation from latency in latently infected calves and rabbits. Increased corticosteroid levels due to stress have a two-pronged effect on reactivation from latency by: (1) directly stimulating viral gene expression and replication, and (2) impairing antiviral immune responses, thus enhancing virus spread and transmission. BoHV-1 encodes several proteins, bICP0, bICP27, gG, UL49.5, and VP8, which interfere with key antiviral innate immune responses in the absence of other viral genes. Furthermore, the ability of BoHV-1 to infect lymphocytes and induce apoptosis, in particular CD4+ T cells, has negative impacts on immune responses during acute infection. BoHV-1 induced immune-suppression can initiate the poly-microbial disorder known as bovine respiratory disease complex, which costs the US cattle industry more than one billion dollars annually. Furthermore, interfering with antiviral responses may promote viral spread to ovaries and the developing fetus, thus enhancing reproductive issues associated with BoHV-1 infection of cows or pregnant cows. The focus of this review is to describe the known mechanisms, direct and indirect, by which BoHV-1 interferes with antiviral immune responses during the course of infection.",2019 May 7,"Jones, Clinton",Front Immunol,,,True
0969d53ac7a447d43b431dbe9744e416de26df38,PMC,B Cells and Antibodies in Kawasaki Disease,http://dx.doi.org/10.3390/ijms20081834,PMC6514959,31013925,CC BY,"The etiology of Kawasaki disease (KD), the leading cause of acquired heart disease in children, is currently unknown. Epidemiology supports a relationship of KD to an infectious disease. Several pathological mechanisms are being considered, including a superantigen response, direct invasion by an infectious etiology or an autoimmune phenomenon. Treating affected patients with intravenous immunoglobulin is effective at reducing the rates of coronary aneurysms. However, the role of B cells and antibodies in KD pathogenesis remains unclear. Murine models are not clear on the role for B cells and antibodies in pathogenesis. Studies on rare aneurysm specimens reveal plasma cell infiltrates. Antibodies generated from these aneurysmal plasma cell infiltrates showed cross-reaction to intracellular inclusions in the bronchial epithelium of a number of pathologic specimens from children with KD. These antibodies have not defined an etiology. Notably, a number of autoantibody responses have been reported in children with KD. Recent studies show acute B cell responses are similar in children with KD compared to children with infections, lending further support of an infectious disease cause of KD. Here, we will review and discuss the inconsistencies in the literature in relation to B cell responses, specific antibodies, and a potential role for humoral immunity in KD pathogenesis or diagnosis.",2019 Apr 13,"['Lindquist, Michael E.', 'Hicar, Mark D.']",Int J Mol Sci,,,True
f12bb7fb01e8ac3137f32d91c94e08a7e90852fb,PMC,Next Generation Vaccines for Infectious Diseases,http://dx.doi.org/10.1155/2019/5890962,PMC6515045,31183388,CC BY,,2019 Apr 30,"['Sautto, Giuseppe A.', 'Kirchenbaum, Greg A.', 'Diotti, Roberta A.', 'Criscuolo, Elena', 'Ferrara, Francesca']",J Immunol Res,,,False
7846c73c25fafce260659a9f9aefbef6b514bf15,PMC,Two Sides of the Coin: Ezrin/Radixin/Moesin and Merlin Control Membrane Structure and Contact Inhibition,http://dx.doi.org/10.3390/ijms20081996,PMC6515277,31018575,CC BY,"The merlin-ERM (ezrin, radixin, moesin) family of proteins plays a central role in linking the cellular membranes to the cortical actin cytoskeleton. Merlin regulates contact inhibition and is an integral part of cell–cell junctions, while ERM proteins, ezrin, radixin and moesin, assist in the formation and maintenance of specialized plasma membrane structures and membrane vesicle structures. These two protein families share a common evolutionary history, having arisen and separated via gene duplication near the origin of metazoa. During approximately 0.5 billion years of evolution, the merlin and ERM family proteins have maintained both sequence and structural conservation to an extraordinary level. Comparing crystal structures of merlin-ERM proteins and their complexes, a picture emerges of the merlin-ERM proteins acting as switchable interaction hubs, assembling protein complexes on cellular membranes and linking them to the actin cytoskeleton. Given the high level of structural conservation between the merlin and ERM family proteins we speculate that they may function together.",2019 Apr 23,"['Michie, Katharine A.', 'Bermeister, Adam', 'Robertson, Neil O.', 'Goodchild, Sophia C.', 'Curmi, Paul M. G.']",Int J Mol Sci,,,True
85d9c134bccd818e9487193754d8c71a710161d6,PMC,"Developments in Transduction, Connectivity and AI/Machine Learning for Point-of-Care Testing",http://dx.doi.org/10.3390/s19081917,PMC6515310,31018573,CC BY,"We review some emerging trends in transduction, connectivity and data analytics for Point-of-Care Testing (POCT) of infectious and non-communicable diseases. The patient need for POCT is described along with developments in portable diagnostics, specifically in respect of Lab-on-chip and microfluidic systems. We describe some novel electrochemical and photonic systems and the use of mobile phones in terms of hardware components and device connectivity for POCT. Developments in data analytics that are applicable for POCT are described with an overview of data structures and recent AI/Machine learning trends. The most important methodologies of machine learning, including deep learning methods, are summarised. The potential value of trends within POCT systems for clinical diagnostics within Lower Middle Income Countries (LMICs) and the Least Developed Countries (LDCs) are highlighted.",2019 Apr 23,"['O’Sullivan, Shane', 'Ali, Zulfiqur', 'Jiang, Xiaoyi', 'Abdolvand, Reza', 'Ünlü, M Selim', 'Plácido da Silva, Hugo', 'Baca, Justin T.', 'Kim, Brian', 'Scott, Simon', 'Sajid, Mohammed Imran', 'Moradian, Sina', 'Mansoorzare, Hakhamanesh', 'Holzinger, Andreas']",Sensors (Basel),,,True
67e55038298b84f9d71e2e300abcead42e725783,PMC,Influenza A virus surface proteins are organized to help penetrate host mucus,http://dx.doi.org/10.7554/eLife.43764,PMC6516830,31084711,CC BY,"Influenza A virus (IAV) enters cells by binding to sialic acid on the cell surface. To accomplish this while avoiding immobilization by sialic acid in host mucus, viruses rely on a balance between the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Although genetic aspects of this balance are well-characterized, little is known about how the spatial organization of these proteins in the viral envelope may contribute. Using site-specific fluorescent labeling and super-resolution microscopy, we show that HA and NA are asymmetrically distributed on the surface of filamentous viruses, creating a spatial organization of binding and cleaving activities that causes viruses to step consistently away from their NA-rich pole. This Brownian ratchet-like diffusion produces persistent directional mobility that resolves the virus’s conflicting needs to both penetrate mucus and stably attach to the underlying cells, potentially contributing to the prevalence of the filamentous phenotype in clinical isolates of IAV.",,"['Vahey, Michael D', 'Fletcher, Daniel A']",eLife.; 8:e43764,,,True
7b1578a9630191d181461fa1552ecff436437856,PMC,Influenza A virus surface proteins are organized to help penetrate host mucus,http://dx.doi.org/10.7554/eLife.43764,PMC6516830,31084711,CC BY,"Influenza A virus (IAV) enters cells by binding to sialic acid on the cell surface. To accomplish this while avoiding immobilization by sialic acid in host mucus, viruses rely on a balance between the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Although genetic aspects of this balance are well-characterized, little is known about how the spatial organization of these proteins in the viral envelope may contribute. Using site-specific fluorescent labeling and super-resolution microscopy, we show that HA and NA are asymmetrically distributed on the surface of filamentous viruses, creating a spatial organization of binding and cleaving activities that causes viruses to step consistently away from their NA-rich pole. This Brownian ratchet-like diffusion produces persistent directional mobility that resolves the virus’s conflicting needs to both penetrate mucus and stably attach to the underlying cells, potentially contributing to the prevalence of the filamentous phenotype in clinical isolates of IAV.",,"['Vahey, Michael D', 'Fletcher, Daniel A']",eLife.; 8:e43764,,,False
b3e5d96ea8379f9890861c6a1c0246f2b93e833a,PMC,Comparative Analysis of Eleven Healthcare-Associated Outbreaks of Middle East Respiratory Syndrome Coronavirus (Mers-Cov) from 2015 to 2017,http://dx.doi.org/10.1038/s41598-019-43586-9,PMC6517387,31089148,CC BY,"Since its emergence in 2012, 2,260 cases and 803 deaths due to Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization. Most cases were due to transmission in healthcare settings, sometimes causing large outbreaks. We analyzed epidemiologic and clinical data of laboratory-confirmed MERS-CoV cases from eleven healthcare-associated outbreaks in the Kingdom of Saudi Arabia and the Republic of Korea between 2015–2017. We quantified key epidemiological differences between outbreaks. Twenty-five percent (n = 105/422) of MERS cases who acquired infection in a hospital setting were healthcare personnel. In multivariate analyses, age ≥65 (OR 4.8, 95%CI: 2.6–8.7) and the presence of underlying comorbidities (OR: 2.7, 95% CI: 1.3–5.7) were associated with increased mortality whereas working as healthcare personnel was protective (OR 0.07, 95% CI: 0.01–0.34). At the start of these outbreaks, the reproduction number ranged from 1.0 to 5.7; it dropped below 1 within 2 to 6 weeks. This study provides a comprehensive characterization of MERS HCA-outbreaks. Our results highlight heterogeneities in the epidemiological profile of healthcare-associated outbreaks. The limitations of our study stress the urgent need for standardized data collection for high-threat respiratory pathogens, such as MERS-CoV.",2019 May 14,"['Bernard-Stoecklin, Sibylle', 'Nikolay, Birgit', 'Assiri, Abdullah', 'Bin Saeed, Abdul Aziz', 'Ben Embarek, Peter Karim', 'El Bushra, Hassan', 'Ki, Moran', 'Malik, Mamunur Rahman', 'Fontanet, Arnaud', 'Cauchemez, Simon', 'Van Kerkhove, Maria D.']",Sci Rep,,,True
fc1c7fe95eca6c5aba24577043ad02c15bfce43a,PMC,Different Associations between DC-SIGN Promoter-336G/A (rs4804803) Polymorphism with Severe Dengue in Asians and South-Central Americans: a Meta-Analysis,http://dx.doi.org/10.3390/ijerph16081475,PMC6518176,31027310,CC BY,"Objective: This study was conducted to identify the association between rs4804803 polymorphism in DC-SIGN with the susceptibility of severe dengue. Methods: A comprehensive search was conducted to identify all eligible papers in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Google Scholar. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used to assess the association. Subgroup analyses were performed by ethnicity. Sensitivity analyses were performed through employing different statistical models (fixed versus random effect model). Results: A total of nine papers and 12 studies, with 1520 severe dengue and 1496 clinical dengue infection were included. The overall meta-analysis revealed significant associations between rs4804803 and severe dengue under the recession (GG versus GA/AA: OR = 0.44, 95%CI, 0.23–0.82) and a codominant model (GG versus AA: OR = 0.43, 95%CI, 0.23–0.81), but sensitivity analysis indicated that the significant pooled ORs were not robust. The subgroup analysis suggested that the carrier of G in rs4804803 was a risk factor for severe dengue under dominant (GG/GA versus AA: OR = 1.86,95%CI, 1.01–3.45), superdominant (GA versus GG/AA: OR = 1.81,95%CI, 1.02–3.21) and a codominant (GA versus AA: OR=1.82,95%CI, 1.02–3.26) models in Asians, while it was a protective factor for severe dengue in South-central Americans under recessive (GG versus GA/AA: OR = 0.27,95%CI, 0.10–0.70) and codominant (GG versus AA: OR=0.24,95%CI, 0.09–0.64) models. The results from subgroup analysis were robust. Conclusions: Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) promoter-336G/A (rs4804803) polymorphism is association with severe dengue, and it acts in different directions for Asians and South-central Americans.",2019 Apr 25,"['Ren, Jiangping', 'Wang, Zhengting', 'Chen, Enfu']",Int J Environ Res Public Health,,,True
51dce3291fc7afaae1c28842c79dc9be97f90ae5,PMC,Factors Influencing the Response to Infectious Diseases: Focusing on the Case of SARS and MERS in South Korea,http://dx.doi.org/10.3390/ijerph16081432,PMC6518241,31013648,CC BY,"Following the 2003 the severe acute respiratory syndrome (SARS) and the 2015 Middle East Respiratory Syndrome (MERS) outbreak in South Korea, this research aims to explore and examine the factors influencing the response to infectious diseases, which encompasses both communicable and non-communicable diseases. Through a qualitative research method, this research categorizes the factors as inputs, processes and outputs and applies them into the 2003 SARS and MERS outbreak in South Korea. As the results conducted meta-analyses to comprehensively analyze the correlations of factors influencing disaster response from a Korean context, the findings show that the legislative factor had direct and indirect influence on the overall process of infectious disease response and that Leadership of the central government, establishment of an intergovernmental response system, the need for communication, information sharing and disclosure and onsite response were identified as key factors influencing effective infectious disease response.",2019 Apr 22,"['Lee, Kyu-Myoung', 'Jung, Kyujin']",Int J Environ Res Public Health,,,True
98db52b9c67490372213988b16fbd56918e3d52f,PMC,Bioaerosols Play a Major Role in the Nasopharyngeal Microbiota Content in Agricultural Environment,http://dx.doi.org/10.3390/ijerph16081375,PMC6518280,30995814,CC BY,"Background: Bioaerosols are a major concern for public health and sampling for exposure assessment purposes is challenging. The nasopharyngeal region could be a potent carrier of long-term bioaerosol exposure agents. This study aimed to evaluate the correlation between nasopharyngeal bacterial flora of swine workers and the swine barns bioaerosol biodiversity. Methods: Air samples from eight swine barns as well as nasopharyngeal swabs from pig workers (n = 25) and from a non-exposed control group (n = 29) were sequenced using 16S rRNA gene high-throughput sequencing. Wastewater treatment plants were used as the industrial, low-dust, non-agricultural environment control to validate the microbial link between the bioaerosol content (air) and the nasopharynxes of workers. Results: A multivariate analysis showed air samples and nasopharyngeal flora of pig workers cluster together, compared to the non-exposed control group. The significance was confirmed with the PERMANOVA statistical test (p-value of 0.0001). Unlike the farm environment, nasopharynx samples from wastewater workers did not cluster with air samples from wastewater treatment plants. The difference in the microbial community of nasopharynx of swine workers and a control group suggest that swine workers are carriers of germs found in bioaerosols. Conclusion: Nasopharynx sampling and microbiota could be used as a proxy of air sampling for exposure assessment studies or for the determination of exposure markers in highly contaminated agricultural environments.",2019 Apr 16,"['Mbareche, Hamza', 'Veillette, Marc', 'Pilote, Jonathan', 'Létourneau, Valérie', 'Duchaine, Caroline']",Int J Environ Res Public Health,,,True
9bfe62e7518a5ca9952dac249961763cd167523f,PMC,"School sessions are correlated with seasonal outbreaks of medically attended respiratory infections: electronic health record time series analysis, Wisconsin 2004–2011",http://dx.doi.org/10.1017/S0950268818003424,PMC6518471,30868998,CC BY,"Increased social contact within school settings is thought to be an important factor in seasonal outbreaks of acute respiratory infection (ARI). To better understand the degree of impact, we analysed electronic health records and compared risks of respiratory infections within communities while schools were in session and out-of-session. A time series analysis of weekly respiratory infection diagnoses from 28 family medicine clinics in Wisconsin showed that people under the age of 65 experienced an increased risk of ARI when schools were in session. For children aged 5–17 years, the risk ratio for the first week of a school session was 1.12 (95% confidence interval (CI) 0.93–1.34), the second week of a session was 1.39 (95% CI 1.15–1.68) and more than 2 weeks into a session was 1.43 (95% CI 1.20–1.71). Less significant increased risk ratios were also observed in young children (0–4 years) and adults (18–64 years). These results were obtained after modelling for baseline seasonal variations in disease prevalence and controlling for short-term changes in ambient temperature and relative humidity. Understanding the mechanisms of seasonality make it easier to predict outbreaks and launch timely public health interventions.",2019 Mar 8,"['Temte, J. L.', 'Meiman, J. G.', 'Gangnon, R. E.']",Epidemiol Infect,,,True
d3ffe6ae419677ea33f6217317c7876f104f806f,PMC,Spatiotemporal distribution of a non-haematophagous bat community and rabies virus circulation: a proposal for urban rabies surveillance in Brazil,http://dx.doi.org/10.1017/S0950268818003229,PMC6518535,30868985,CC BY,"In Brazil, rabies surveillance is based on monitoring domestic and wild animals, although the most prevalent lineage of the rabies virus (RABV) currently diagnosed in Brazil is associated with bats, particularly non-haematophagous bats. Disease control is based on the mass vaccination of dogs and cats. We used data collected by the passive surveillance system of the city of Campinas from 2011 to 2015, to describe the temporal and geographic distributions of the bat specimens and RABV and discuss the current rabies surveillance with the advent of the declaration of canine and feline rabies-free areas in Brazil. We described the species, locations and health statuses of the collected bat specimens. Moreover, all samples were submitted for RABV diagnosis. Then, we performed a time series decomposition for each bat family. Additionally, we determined the spatiotemporal relative risk for RABV infection using the ratio of the kernel-smoothed estimates of spatiotemporal densities of RABV-positive and RABV-negative bats. From the 2537 bat specimens, the most numerous family was Molossidae (72%), followed by Vespertilionidae (14%) and Phyllostomidae (13%). The bat families behaved differently in terms of seasonal and spatial patterns. The distribution of bats varied geographically in the urban environment, with Molossidae and Phyllostomidae being observed downtown and Vespertilionidae being observed in peripheral zones. Concurrently, a significant relative risk of RABV infection was observed downtown for Vespertilionidae and in peripheral zones for Molossidae. No RABV-positive sample clusters were observed. As a result of the official declaration of RABV-free areas in southern Brazil, mass dog and cat vaccinations are expected to halt in the near future. This stoppage would make most dog and cat populations susceptible to other RABV lineages, such as those maintained by non-haematophagous bats. In this scenario, all information available on bats and RABV distribution in urban areas is essential. Currently, few studies have been conducted. Some local health authorities, such as that in Campinas, are spontaneously basing their surveillance efforts on bat rabies, which is the alternative in reality scenario of increased susceptibility to bat-associated RABV that is developing in Brazil.",2019 Mar 8,"['Dias, R. A.', 'Rocha, F.', 'Ulloa-Stanojlovic, F. M.', 'Nitsche, A.', 'Castagna, C.', 'de Lucca, T.', 'Rodrigues, R. C. A.']",Epidemiol Infect,,,True
d76707259c99c13efac920c66169aa4560438499,PMC,"Temporal dynamics of Middle East respiratory syndrome coronavirus in the Arabian Peninsula, 2012–2017",http://dx.doi.org/10.1017/S0950268818002728,PMC6518552,30293534,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) remains a notable disease and poses a significant threat to global public health. The Arabian Peninsula is considered a major global epicentre for the disease and the virus has crossed regional and continental boundaries since 2012. In this study, we focused on exploring the temporal dynamics of MERS-CoV in human populations in the Arabian Peninsula between 2012 and 2017, using publicly available data on case counts and combining two analytical methods. Disease progression was assessed by quantifying the time-dependent reproductive number (TD-Rs), while case series temporal pattern was modelled using the AutoRegressive Integrated Moving Average (ARIMA). We accounted for geographical variability between three major affected regions in Saudi Arabia including Eastern Province, Riyadh and Makkah. In Saudi Arabia, the epidemic size was large with TD-Rs >1, indicating significant spread until 2017. In both Makkah and Riyadh regions, the epidemic progression reached its peak in April 2014 (TD-Rs > 7), during the highest incidence period of MERS-CoV cases. In Eastern Province, one unique super-spreading event (TD-R > 10) was identified in May 2013, which comprised of the most notable cases of human-to-human transmission. Best-fitting ARIMA model inferred statistically significant biannual seasonality in Riyadh region, a region characterised by heavy seasonal camel-related activities. However, no statistical evidence of seasonality was identified in Eastern Province and Makkah. Instead, both areas were marked by an endemic pattern of cases with sporadic outbreaks. Our study suggested new insights into the epidemiology of the virus, including inferences about epidemic progression and evidence for seasonality. Despite the inherent limitations of the available data, our conclusions provide further guidance to currently implement risk-based surveillance in high-risk populations and, subsequently, improve related interventions strategies against the epidemic at country and regional levels.",2018 Oct 8,"['Alkhamis, M. A.', 'Fernández-Fontelo, A.', 'VanderWaal, K.', 'Abuhadida, S.', 'Puig, P.', 'Alba-Casals, A.']",Epidemiol Infect,,,True
a648ceb9b7971f6694d45afb369dc849d5894095,PMC,Letter to the editor in response to ‘Reconstruction and prediction of viral disease epidemics’,http://dx.doi.org/10.1017/S095026881900013X,PMC6518571,30869030,CC BY,,2019 Feb 22,"Perkins, T. Alex",Epidemiol Infect,,,False
24de2f3f8107492057953a49ec7182514e9ff95a,PMC,Prevalence of comorbidities in cases of Middle East respiratory syndrome coronavirus: a retrospective study,http://dx.doi.org/10.1017/S0950268818002923,PMC6518603,30394248,CC BY,"The Middle East respiratory syndrome coronavirus (MERS-CoV) is a life-threatening respiratory disease with a high case fatality rate; however, its risk factors remain unclear. We aimed to explore the influence of demographic factors, clinical manifestations and underlying comorbidities on mortality in MERS-CoV patients. Retrospective chart reviews were performed to identify all laboratory-confirmed cases of MERS-COV infection in Saudi Arabia that were reported to the Ministry of Health of Saudi Arabia between 23 April 2014 and 7 June 2016. Statistical analyses were conducted to assess the effect of sex, age, clinical presentation and comorbidities on mortality from MERS-CoV. A total of 281 confirmed MERS-CoV cases were identified: 167 (59.4%) patients were male and 55 (20%) died. Mortality predominantly occurred among Saudi nationals and older patients and was significantly associated with respiratory failure and shortness of breath. Of the 281 confirmed cases, 160 (56.9%) involved comorbidities, wherein diabetes mellitus, hypertension, ischemic heart disease, congestive heart failure, end-stage renal disease and chronic kidney disease were significantly associated with mortality from MERS-CoV and two or three comorbidities significantly affected the fatality rates from MERS-CoV. The findings of this study show that old age and the existence of underlying comorbidities significantly increase mortality from MERS-CoV.",2018 Nov 5,"['Alqahtani, F.Y.', 'Aleanizy, F.S.', 'Ali El Hadi Mohamed, R.', 'Alanazi, M. S.', 'Mohamed, N.', 'Alrasheed, M. M.', 'Abanmy, N.', 'Alhawassi, T.']",Epidemiol Infect,,,True
e3c77bacc976ab718dae1e74bedb00219d701c3e,PMC,"Time-series modelling and forecasting of hand, foot and mouth disease cases in China from 2008 to 2018",http://dx.doi.org/10.1017/S095026881800362X,PMC6518604,30868999,CC BY,"Seasonal autoregressive-integrated moving average (SARIMA) has been widely used to model and forecast incidence of infectious diseases in time-series analysis. This study aimed to model and forecast monthly cases of hand, foot and mouth disease (HFMD) in China. Monthly incidence HFMD cases in China from May 2008 to August 2018 were analysed with the SARIMA model. A seasonal variation of HFMD incidence was found from May 2008 to August 2018 in China, with a predominant peak from April to July and a trough from January to March. In addition, the annual peak occurred periodically with a large annual peak followed by a relatively small annual peak. A SARIMA model of SARIMA (1, 1, 2) (0, 1, 1)(12) was identified, and the mean error rate and determination coefficient were 16.86% and 94.27%, respectively. There was an annual periodicity and seasonal variation of HFMD incidence in China, which could be predicted well by a SARIMA (1, 1, 2) (0, 1, 1)(12) model.",2019 Jan 31,"['Tian, C. W.', 'Wang, H.', 'Luo, X. M.']",Epidemiol Infect,,,True
5a57a6330daa19227fb5011f690e68accf1c4b1d,PMC,Global status of Middle East respiratory syndrome coronavirus in dromedary camels: a systematic review,http://dx.doi.org/10.1017/S095026881800345X,PMC6518605,30869000,CC BY,"Dromedary camels have been shown to be the main reservoir for human Middle East respiratory syndrome (MERS) infections. This systematic review aims to compile and analyse all published data on MERS-coronavirus (CoV) in the global camel population to provide an overview of current knowledge on the distribution, spread and risk factors of infections in dromedary camels. We included original research articles containing laboratory evidence of MERS-CoV infections in dromedary camels in the field from 2013 to April 2018. In general, camels only show minor clinical signs of disease after being infected with MERS-CoV. Serological evidence of MERS-CoV in camels has been found in 20 countries, with molecular evidence for virus circulation in 13 countries. The seroprevalence of MERS-CoV antibodies increases with age in camels, while the prevalence of viral shedding as determined by MERS-CoV RNA detection in nasal swabs decreases. In several studies, camels that were sampled at animal markets or quarantine facilities were seropositive more often than camels at farms as well as imported camels vs. locally bred camels. Some studies show a relatively higher seroprevalence and viral detection during the cooler winter months. Knowledge of the animal reservoir of MERS-CoV is essential to develop intervention and control measures to prevent human infections.",2019 Feb 21,"['Sikkema, R. S.', 'Farag, E. A. B. A.', 'Islam, Mazharul', 'Atta, Muzzamil', 'Reusken, C. B. E. M.', 'Al-Hajri, Mohd M.', 'Koopmans, M. P. G.']",Epidemiol Infect,,,True
df3fd6661b2d0bd3a51c54b4cdba7be250e52746,PMC,Delivery of SA35 and SA40 peptides in mice enhances humoral and cellular immune responses and confers protection against Cryptosporidium parvum infection,http://dx.doi.org/10.1186/s13071-019-3486-8,PMC6518611,31092283,CC BY,"BACKGROUND: Cryptosporidium parvum is a major cause of diarrhea in children and ruminants at the earliest stages of life. Maternal antibodies represent the main shield of neonate mammals for most of the infections. Two recombinant antigens (SA35 and SA40), portions of two C. parvum proteins, were tested for their ability to induce immune responses in adult mice and for protection on neonate BALB/c mice born from females immunised by mucosal delivery of both peptides. METHODS: Adult BALB/c mice were intraperitoneally immunised with SA35 and SA40, separately or mixed, and their immune response was characterised. Furthermore, BALB/c pregnant mice were immunised by mucosal delivery with an SA35/40 mix, before and during pregnancy. Soon after birth, their offspring were infected with two doses (1 × 10(5) and 5 × 10(3)) of C. parvum oocysts and the parasitic burden was determined at 5 and 9 days post-infection. RESULTS: Intraperitoneal immunisation with SA35 and SA40 induced specific IgG and IgG1 in serum, specific IgA in the intestinal mucosa, increase of CD3+/CD4+ and CD30+ cells in splenocytes, which produced IFN-γ. Neonates born from immunised mice and infected with 1 × 10(5) oocysts showed a significant reduction of oocysts and intestinal forms (23 and 42%, respectively). A reduction of all parasitic forms (96%; P < 0.05) was observed when neonates were infected with 5 × 10(3) oocysts. CONCLUSIONS: SA35 and SA40 peptides induce specific humoral and cell-mediated immune responses to C. parvum in adult mice. Moreover, mucosal administration of the SA35/40 mix in pregnant mice reduces C. parvum burden in their litters.",2019 May 15,"['Tosini, Fabio', 'Ludovisi, Alessandra', 'Tonanzi, Daniele', 'Amati, Marco', 'Cherchi, Simona', 'Pozio, Edoardo', 'Gómez-Morales, Maria Angeles']",Parasit Vectors,,,True
fbb1af3990778d2061c8466c3a5156fececf146b,PMC,Bending the epidemic curve: advancements and opportunities to reduce the threat of emerging pathogens,http://dx.doi.org/10.1017/S095026881900058X,PMC6518771,30955504,CC BY,This invited editorial introduces a special issue of Epidemiology & Infection while also discussing advances in emerging infectious diseases.,2019 Apr 3,"['Desai, Angel N.', 'Madoff, Lawrence C.']",Epidemiol Infect,,,True
837935e5f921344c58f824f262566bd688ceddb2,PMC,"Seroprevalence of hepatitis E virus in dromedary camels, Bedouins, Muslim Arabs and Jews in Israel, 2009–2017",http://dx.doi.org/10.1017/S0950268819000062,PMC6518832,30869027,CC BY,"Hepatitis E virus (HEV) is an emerging cause of viral hepatitis worldwide. Recently, HEV-7 has been shown to infect camels and humans. We studied HEV seroprevalence in dromedary camels and among Bedouins, Arabs (Muslims, none-Bedouins) and Jews and assessed factors associated with anti-HEV seropositivity. Serum samples from dromedary camels (n = 86) were used to determine camel anti-HEV IgG and HEV RNA positivity. Human samples collected between 2009 and 2016 from >20 years old Bedouins (n = 305), non-Bedouin Arabs (n = 320) and Jews (n = 195), were randomly selected using an age-stratified sampling design. Human HEV IgG levels were determined using Wantai IgG ELISA assay. Of the samples obtained from camels, 68.6% were anti-HEV positive. Among the human populations, Bedouins and non-Bedouin Arabs had a significantly higher prevalence of HEV antibodies (21.6% and 15.0%, respectively) compared with the Jewish population (3.1%). Seropositivity increased significantly with age in all human populations, reaching 47.6% and 34.8% among ⩾40 years old, in Bedouins and non-Bedouin Arabs, respectively. The high seropositivity in camels and in ⩾40 years old Bedouins and non-Bedouin Arabs suggests that HEV is endemic in Israel. The low HEV seroprevalence in Jews could be attributed to higher socio-economic status.",2019 Feb 22,"['Bassal, R.', 'Wax, M.', 'Shirazi, R.', 'Shohat, T.', 'Cohen, D.', 'David, D.', 'Abu-Mouch, S.', 'Abu-Ghanem, Y.', 'Mendelson, E.', 'Ben-Ari, Z.', 'Mor, O.']",Epidemiol Infect,,,True
5efda07d4d247024ea5afb007bd2a5f05501ce8f,PMC,Quantitative Temporal Proteomic Analysis of Vaccinia Virus Infection Reveals Regulation of Histone Deacetylases by an Interferon Antagonist,http://dx.doi.org/10.1016/j.celrep.2019.04.042,PMC6518873,31067474,CC BY,"Vaccinia virus (VACV) has numerous immune evasion strategies, including multiple mechanisms of inhibition of interferon regulatory factor 3 (IRF-3), nuclear factor κB (NF-κB), and type I interferon (IFN) signaling. Here, we use highly multiplexed proteomics to quantify ∼9,000 cellular proteins and ∼80% of viral proteins at seven time points throughout VACV infection. A total of 265 cellular proteins are downregulated >2-fold by VACV, including putative natural killer cell ligands and IFN-stimulated genes. Two-thirds of these viral targets, including class II histone deacetylase 5 (HDAC5), are degraded proteolytically during infection. In follow-up analysis, we demonstrate that HDAC5 restricts replication of both VACV and herpes simplex virus type 1. By generating a protein-based temporal classification of VACV gene expression, we identify protein C6, a multifunctional IFN antagonist, as being necessary and sufficient for proteasomal degradation of HDAC5. Our approach thus identifies both a host antiviral factor and a viral mechanism of innate immune evasion.",2019 May 7,"['Soday, Lior', 'Lu, Yongxu', 'Albarnaz, Jonas D.', 'Davies, Colin T.R.', 'Antrobus, Robin', 'Smith, Geoffrey L.', 'Weekes, Michael P.']",Cell Rep,,,False
ba0f23393bc8673f2e26b02053f6135e5a2f6a44,PMC,Quantitative Temporal Proteomic Analysis of Vaccinia Virus Infection Reveals Regulation of Histone Deacetylases by an Interferon Antagonist,http://dx.doi.org/10.1016/j.celrep.2019.04.042,PMC6518873,31067474,CC BY,"Vaccinia virus (VACV) has numerous immune evasion strategies, including multiple mechanisms of inhibition of interferon regulatory factor 3 (IRF-3), nuclear factor κB (NF-κB), and type I interferon (IFN) signaling. Here, we use highly multiplexed proteomics to quantify ∼9,000 cellular proteins and ∼80% of viral proteins at seven time points throughout VACV infection. A total of 265 cellular proteins are downregulated >2-fold by VACV, including putative natural killer cell ligands and IFN-stimulated genes. Two-thirds of these viral targets, including class II histone deacetylase 5 (HDAC5), are degraded proteolytically during infection. In follow-up analysis, we demonstrate that HDAC5 restricts replication of both VACV and herpes simplex virus type 1. By generating a protein-based temporal classification of VACV gene expression, we identify protein C6, a multifunctional IFN antagonist, as being necessary and sufficient for proteasomal degradation of HDAC5. Our approach thus identifies both a host antiviral factor and a viral mechanism of innate immune evasion.",2019 May 7,"['Soday, Lior', 'Lu, Yongxu', 'Albarnaz, Jonas D.', 'Davies, Colin T.R.', 'Antrobus, Robin', 'Smith, Geoffrey L.', 'Weekes, Michael P.']",Cell Rep,,,False
9ff6863b239e533b93dd1147c0c9a36a01d7ad66,PMC,Quantitative Temporal Proteomic Analysis of Vaccinia Virus Infection Reveals Regulation of Histone Deacetylases by an Interferon Antagonist,http://dx.doi.org/10.1016/j.celrep.2019.04.042,PMC6518873,31067474,CC BY,"Vaccinia virus (VACV) has numerous immune evasion strategies, including multiple mechanisms of inhibition of interferon regulatory factor 3 (IRF-3), nuclear factor κB (NF-κB), and type I interferon (IFN) signaling. Here, we use highly multiplexed proteomics to quantify ∼9,000 cellular proteins and ∼80% of viral proteins at seven time points throughout VACV infection. A total of 265 cellular proteins are downregulated >2-fold by VACV, including putative natural killer cell ligands and IFN-stimulated genes. Two-thirds of these viral targets, including class II histone deacetylase 5 (HDAC5), are degraded proteolytically during infection. In follow-up analysis, we demonstrate that HDAC5 restricts replication of both VACV and herpes simplex virus type 1. By generating a protein-based temporal classification of VACV gene expression, we identify protein C6, a multifunctional IFN antagonist, as being necessary and sufficient for proteasomal degradation of HDAC5. Our approach thus identifies both a host antiviral factor and a viral mechanism of innate immune evasion.",2019 May 7,"['Soday, Lior', 'Lu, Yongxu', 'Albarnaz, Jonas D.', 'Davies, Colin T.R.', 'Antrobus, Robin', 'Smith, Geoffrey L.', 'Weekes, Michael P.']",Cell Rep,,,True
3735055ce30bb1cb8aa6ef4fb1731dcc8219df35,PMC,Factors Associated With Time to Elimination of Porcine Epidemic Diarrhea Virus in Individual Ontario Swine Herds Based on Surveillance Data,http://dx.doi.org/10.3389/fvets.2019.00139,PMC6518961,31139635,CC BY,"Porcine epidemic diarrhea virus (PEDV) emerged into Canada in January of 2014. The virus was considered to be of high importance and the number of new cases were tracked using different mechanisms by stakeholders such as veterinary services from the provincial government and the swine industry. In addition to the initial date of infection, veterinary organizations in the swine industry maintained a disease control program (DCP) database that contained the date of declaration of freedom from PEDV in individual herds. Such data allowed for the determination of the duration of PEDV infection in individual herds based on herd type, year and season of diagnosis. Therefore, the objective of this study was to determine time to PEDV elimination in Ontario swine herds infected between 2014 and 2017, on the basis of records from the DCP database; and to identify factors associated with the likelihood of elimination. Duration of time to eliminate PEDV was estimated using Kaplan-Meier survival curves. The final Cox's proportional hazard model included herd type, season and year of diagnosis. The hazard of PEDV elimination for premises that were farrow-to-wean was 3.36 times larger (P-value: 0.044, 95% CI: 1.03, 10.93) than for farrow-to-feeder herds. Herds diagnosed in the summer and fall had hazard ratios of 1.40 (P-value: 0.044, 95% CI: 1.03, 10.93) and 7.32 (P-value: <0.001, 95% CI: 3.12, 17.18), respectively compared to herds diagnosed in the winter months. The hazard ratio for herds diagnosed in 2015 was 0.54 (P-value: 0.015, 95% CI: 0.33, 0.89) compared to herds diagnosed in 2014. Factors associated with time to elimination are likely reflective of the complexity of infection control practices applied in herds with different demographics and population structures, seasonal variability in the pathogen transmissibility, and the availability of resources to manage an emerging production-limiting disease. The median times to elimination were relatively long, which could be due to how it was measured, decisions made at the level of individual herds or delays related to reporting PEDV elimination. Design of control measures for production-limiting diseases at the regional level should take these factors into consideration.",2019 May 8,"['Perri, Amanda M.', 'Poljak, Zvonimir', 'Dewey, Cate', 'Harding, John C. S.', ""O'Sullivan, Terri L.""]",Front Vet Sci,,,True
d8a0e6a4cc626dfe6090ea49ce8b920eee3f98e1,PMC,"Cohort profile: Studies of Work Environment and Disease Epidemiology-Infections (SWEDE-I), a prospective cohort on employed adults in Sweden",http://dx.doi.org/10.1371/journal.pone.0217012,PMC6519895,31091278,CC BY,"The aim of this article is to provide a detailed description of the SWEDE-I cohort, a prospective study designed to investigate work-related risk factors for transmission of viral infections. A total of 2,237 subjects aged 25–64, working and residing in Eskilstuna (central Sweden), enrolled in the study in August 2011. They filled in five detailed questionnaires including information on demography, personal characteristics, work tasks, work place, contact patterns, family structure, health status, physical activity and diet. During a 9-month follow-up period, the participants self-reported—via internet or telephone—any onset of fever, upper respiratory tract infection, or gastroenteritis immediately as they occurred. For each disease episode, the participants were asked to submit a self-sampled nasal swab for viral diagnosis. In total, 1,733 disease reports were recorded and 1,843 nasal swabs were received, of which 48% tested positive for one or more of 14 analyzed viruses. The cohort has been used to date to study diet, sleep and physical activity as determinants for upper respiratory tract infections. Analyses of contact patterns and occupational circumstances as risk factors for the transmission of infections are ongoing. The SWEDE-I study should be seen as a first pioneering effort to provide new insight in the epidemiology and prevention of viral infections. Potential joint collaborations can be discussed with the principal investigators.",2019 May 15,"['Ghilotti, Francesca', 'Julander, Anneli', 'Gustavsson, Per', 'Linde, Annika', 'Nyrén, Olof', 'Plymoth, Amelie']",PLoS One,,,True
0d59b59865ae40541944da35538b2b9a1b9fb6a6,PMC,"Cohort profile: Studies of Work Environment and Disease Epidemiology-Infections (SWEDE-I), a prospective cohort on employed adults in Sweden",http://dx.doi.org/10.1371/journal.pone.0217012,PMC6519895,31091278,CC BY,"The aim of this article is to provide a detailed description of the SWEDE-I cohort, a prospective study designed to investigate work-related risk factors for transmission of viral infections. A total of 2,237 subjects aged 25–64, working and residing in Eskilstuna (central Sweden), enrolled in the study in August 2011. They filled in five detailed questionnaires including information on demography, personal characteristics, work tasks, work place, contact patterns, family structure, health status, physical activity and diet. During a 9-month follow-up period, the participants self-reported—via internet or telephone—any onset of fever, upper respiratory tract infection, or gastroenteritis immediately as they occurred. For each disease episode, the participants were asked to submit a self-sampled nasal swab for viral diagnosis. In total, 1,733 disease reports were recorded and 1,843 nasal swabs were received, of which 48% tested positive for one or more of 14 analyzed viruses. The cohort has been used to date to study diet, sleep and physical activity as determinants for upper respiratory tract infections. Analyses of contact patterns and occupational circumstances as risk factors for the transmission of infections are ongoing. The SWEDE-I study should be seen as a first pioneering effort to provide new insight in the epidemiology and prevention of viral infections. Potential joint collaborations can be discussed with the principal investigators.",2019 May 15,"['Ghilotti, Francesca', 'Julander, Anneli', 'Gustavsson, Per', 'Linde, Annika', 'Nyrén, Olof', 'Plymoth, Amelie']",PLoS One,,,False
3930a3496363e8e8b5af3c340fc1ea7a3efb1ad3,PMC,"Cohort profile: Studies of Work Environment and Disease Epidemiology-Infections (SWEDE-I), a prospective cohort on employed adults in Sweden",http://dx.doi.org/10.1371/journal.pone.0217012,PMC6519895,31091278,CC BY,"The aim of this article is to provide a detailed description of the SWEDE-I cohort, a prospective study designed to investigate work-related risk factors for transmission of viral infections. A total of 2,237 subjects aged 25–64, working and residing in Eskilstuna (central Sweden), enrolled in the study in August 2011. They filled in five detailed questionnaires including information on demography, personal characteristics, work tasks, work place, contact patterns, family structure, health status, physical activity and diet. During a 9-month follow-up period, the participants self-reported—via internet or telephone—any onset of fever, upper respiratory tract infection, or gastroenteritis immediately as they occurred. For each disease episode, the participants were asked to submit a self-sampled nasal swab for viral diagnosis. In total, 1,733 disease reports were recorded and 1,843 nasal swabs were received, of which 48% tested positive for one or more of 14 analyzed viruses. The cohort has been used to date to study diet, sleep and physical activity as determinants for upper respiratory tract infections. Analyses of contact patterns and occupational circumstances as risk factors for the transmission of infections are ongoing. The SWEDE-I study should be seen as a first pioneering effort to provide new insight in the epidemiology and prevention of viral infections. Potential joint collaborations can be discussed with the principal investigators.",2019 May 15,"['Ghilotti, Francesca', 'Julander, Anneli', 'Gustavsson, Per', 'Linde, Annika', 'Nyrén, Olof', 'Plymoth, Amelie']",PLoS One,,,False
22c4eb219966e3ab37726362c48b0d8f918d4b52,PMC,"Cohort profile: Studies of Work Environment and Disease Epidemiology-Infections (SWEDE-I), a prospective cohort on employed adults in Sweden",http://dx.doi.org/10.1371/journal.pone.0217012,PMC6519895,31091278,CC BY,"The aim of this article is to provide a detailed description of the SWEDE-I cohort, a prospective study designed to investigate work-related risk factors for transmission of viral infections. A total of 2,237 subjects aged 25–64, working and residing in Eskilstuna (central Sweden), enrolled in the study in August 2011. They filled in five detailed questionnaires including information on demography, personal characteristics, work tasks, work place, contact patterns, family structure, health status, physical activity and diet. During a 9-month follow-up period, the participants self-reported—via internet or telephone—any onset of fever, upper respiratory tract infection, or gastroenteritis immediately as they occurred. For each disease episode, the participants were asked to submit a self-sampled nasal swab for viral diagnosis. In total, 1,733 disease reports were recorded and 1,843 nasal swabs were received, of which 48% tested positive for one or more of 14 analyzed viruses. The cohort has been used to date to study diet, sleep and physical activity as determinants for upper respiratory tract infections. Analyses of contact patterns and occupational circumstances as risk factors for the transmission of infections are ongoing. The SWEDE-I study should be seen as a first pioneering effort to provide new insight in the epidemiology and prevention of viral infections. Potential joint collaborations can be discussed with the principal investigators.",2019 May 15,"['Ghilotti, Francesca', 'Julander, Anneli', 'Gustavsson, Per', 'Linde, Annika', 'Nyrén, Olof', 'Plymoth, Amelie']",PLoS One,,,True
53aa338c7e4939eaa2123709e7396252bc1bcd7a,PMC,"Cohort profile: Studies of Work Environment and Disease Epidemiology-Infections (SWEDE-I), a prospective cohort on employed adults in Sweden",http://dx.doi.org/10.1371/journal.pone.0217012,PMC6519895,31091278,CC BY,"The aim of this article is to provide a detailed description of the SWEDE-I cohort, a prospective study designed to investigate work-related risk factors for transmission of viral infections. A total of 2,237 subjects aged 25–64, working and residing in Eskilstuna (central Sweden), enrolled in the study in August 2011. They filled in five detailed questionnaires including information on demography, personal characteristics, work tasks, work place, contact patterns, family structure, health status, physical activity and diet. During a 9-month follow-up period, the participants self-reported—via internet or telephone—any onset of fever, upper respiratory tract infection, or gastroenteritis immediately as they occurred. For each disease episode, the participants were asked to submit a self-sampled nasal swab for viral diagnosis. In total, 1,733 disease reports were recorded and 1,843 nasal swabs were received, of which 48% tested positive for one or more of 14 analyzed viruses. The cohort has been used to date to study diet, sleep and physical activity as determinants for upper respiratory tract infections. Analyses of contact patterns and occupational circumstances as risk factors for the transmission of infections are ongoing. The SWEDE-I study should be seen as a first pioneering effort to provide new insight in the epidemiology and prevention of viral infections. Potential joint collaborations can be discussed with the principal investigators.",2019 May 15,"['Ghilotti, Francesca', 'Julander, Anneli', 'Gustavsson, Per', 'Linde, Annika', 'Nyrén, Olof', 'Plymoth, Amelie']",PLoS One,,,False
b036ad57f875ee14fd3bef635efad5811fab932c,PMC,"Cohort profile: Studies of Work Environment and Disease Epidemiology-Infections (SWEDE-I), a prospective cohort on employed adults in Sweden",http://dx.doi.org/10.1371/journal.pone.0217012,PMC6519895,31091278,CC BY,"The aim of this article is to provide a detailed description of the SWEDE-I cohort, a prospective study designed to investigate work-related risk factors for transmission of viral infections. A total of 2,237 subjects aged 25–64, working and residing in Eskilstuna (central Sweden), enrolled in the study in August 2011. They filled in five detailed questionnaires including information on demography, personal characteristics, work tasks, work place, contact patterns, family structure, health status, physical activity and diet. During a 9-month follow-up period, the participants self-reported—via internet or telephone—any onset of fever, upper respiratory tract infection, or gastroenteritis immediately as they occurred. For each disease episode, the participants were asked to submit a self-sampled nasal swab for viral diagnosis. In total, 1,733 disease reports were recorded and 1,843 nasal swabs were received, of which 48% tested positive for one or more of 14 analyzed viruses. The cohort has been used to date to study diet, sleep and physical activity as determinants for upper respiratory tract infections. Analyses of contact patterns and occupational circumstances as risk factors for the transmission of infections are ongoing. The SWEDE-I study should be seen as a first pioneering effort to provide new insight in the epidemiology and prevention of viral infections. Potential joint collaborations can be discussed with the principal investigators.",2019 May 15,"['Ghilotti, Francesca', 'Julander, Anneli', 'Gustavsson, Per', 'Linde, Annika', 'Nyrén, Olof', 'Plymoth, Amelie']",PLoS One,,,False
37a9917cf6525a9daa87e8f3d14393d0fe0a0147,PMC,"Cohort profile: Studies of Work Environment and Disease Epidemiology-Infections (SWEDE-I), a prospective cohort on employed adults in Sweden",http://dx.doi.org/10.1371/journal.pone.0217012,PMC6519895,31091278,CC BY,"The aim of this article is to provide a detailed description of the SWEDE-I cohort, a prospective study designed to investigate work-related risk factors for transmission of viral infections. A total of 2,237 subjects aged 25–64, working and residing in Eskilstuna (central Sweden), enrolled in the study in August 2011. They filled in five detailed questionnaires including information on demography, personal characteristics, work tasks, work place, contact patterns, family structure, health status, physical activity and diet. During a 9-month follow-up period, the participants self-reported—via internet or telephone—any onset of fever, upper respiratory tract infection, or gastroenteritis immediately as they occurred. For each disease episode, the participants were asked to submit a self-sampled nasal swab for viral diagnosis. In total, 1,733 disease reports were recorded and 1,843 nasal swabs were received, of which 48% tested positive for one or more of 14 analyzed viruses. The cohort has been used to date to study diet, sleep and physical activity as determinants for upper respiratory tract infections. Analyses of contact patterns and occupational circumstances as risk factors for the transmission of infections are ongoing. The SWEDE-I study should be seen as a first pioneering effort to provide new insight in the epidemiology and prevention of viral infections. Potential joint collaborations can be discussed with the principal investigators.",2019 May 15,"['Ghilotti, Francesca', 'Julander, Anneli', 'Gustavsson, Per', 'Linde, Annika', 'Nyrén, Olof', 'Plymoth, Amelie']",PLoS One,,,False
2750bbcb6ecf63b2519523a2a63145167c5f8d38,PMC,Mechanism of Inhibition of Ebola Virus RNA-Dependent RNA Polymerase by Remdesivir,http://dx.doi.org/10.3390/v11040326,PMC6520719,30987343,CC BY,"Remdesivir (GS-5734) is a 1′-cyano-substituted adenosine nucleotide analogue prodrug that shows broad-spectrum antiviral activity against several RNA viruses. This compound is currently under clinical development for the treatment of Ebola virus disease (EVD). While antiviral effects have been demonstrated in cell culture and in non-human primates, the mechanism of action of Ebola virus (EBOV) inhibition for remdesivir remains to be fully elucidated. The EBOV RNA-dependent RNA polymerase (RdRp) complex was recently expressed and purified, enabling biochemical studies with the relevant triphosphate (TP) form of remdesivir and its presumptive target. In this study, we confirmed that remdesivir-TP is able to compete for incorporation with adenosine triphosphate (ATP). Enzyme kinetics revealed that EBOV RdRp and respiratory syncytial virus (RSV) RdRp incorporate ATP and remdesivir-TP with similar efficiencies. The selectivity of ATP against remdesivir-TP is ~4 for EBOV RdRp and ~3 for RSV RdRp. In contrast, purified human mitochondrial RNA polymerase (h-mtRNAP) effectively discriminates against remdesivir-TP with a selectivity value of ~500-fold. For EBOV RdRp, the incorporated inhibitor at position i does not affect the ensuing nucleotide incorporation event at position i+1. For RSV RdRp, we measured a ~6-fold inhibition at position i+1 although RNA synthesis was not terminated. Chain termination was in both cases delayed and was seen predominantly at position i+5. This pattern is specific to remdesivir-TP and its 1′-cyano modification. Compounds with modifications at the 2′-position show different patterns of inhibition. While 2′-C-methyl-ATP is not incorporated, ara-ATP acts as a non-obligate chain terminator and prevents nucleotide incorporation at position i+1. Taken together, our biochemical data indicate that the major contribution to EBOV RNA synthesis inhibition by remdesivir can be ascribed to delayed chain termination. The long distance of five residues between the incorporated nucleotide analogue and its inhibitory effect warrant further investigation.",2019 Apr 4,"['Tchesnokov, Egor P.', 'Feng, Joy Y.', 'Porter, Danielle P.', 'Götte, Matthias']",Viruses,,,True
35fd57d62eba3f9b7de6cd27ac5fe63a478a4197,PMC,The N-Terminal Domain of Spike Protein Is Not the Enteric Tropism Determinant for Transmissible Gastroenteritis Virus in Piglets,http://dx.doi.org/10.3390/v11040313,PMC6520731,30935078,CC BY,"Transmissible gastroenteritis virus (TGEV) is the etiologic agent of transmissible gastroenteritis in pigs, and the N-terminal domain of TGEV spike protein is generally recognized as both the virulence determinant and enteric tropism determinant. Here, we assembled a full-length infectious cDNA clone of TGEV in a bacterial artificial chromosome. Using a novel approach, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) systems efficiently and rapidly rescued another recombinant virus with a 224-amino-acid deletion in the N-terminal domain of the TGEV Spike gene (S_NTD224), which is analogous to the N-terminal domain of porcine respiratory coronavirus. S_NTD224 notably affected the TGEV growth kinetics in PK-15 cells but was not essential for recombinant virus survival. In animal experiments with 13 two-day-old piglets, the TGEV recombinant viruses with/without S_NTD224 deletion induced obvious clinical signs and mortality. Together, our results directly demonstrated that S_NTD224 of TGEV mildly influenced TGEV virulence but was not the enteric tropism determinant and provide new insights for the development of a new attenuated vaccine against TGEV. Importantly, the optimized reverse genetics platform used in this study will simplify the construction of mutant infectious clones and help accelerate progress in coronavirus research.",2019 Mar 30,"['Wang, Gang', 'Liang, Rui', 'Liu, Ziwei', 'Shen, Zhou', 'Shi, Jiale', 'Shi, Yuejun', 'Deng, Feng', 'Xiao, Shaobo', 'Fu, Zhen F.', 'Peng, Guiqing']",Viruses,,,True
78f2ffac0503062687663d82d65f846290fb9c45,PMC,Lack of Middle East Respiratory Syndrome Coronavirus Transmission in Rabbits,http://dx.doi.org/10.3390/v11040381,PMC6520746,31022948,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) transmission from dromedaries to humans has resulted in major outbreaks in the Middle East. Although some other livestock animal species have been shown to be susceptible to MERS-CoV, it is not fully understood why the spread of the virus in these animal species has not been observed in the field. In this study, we used rabbits to further characterize the transmission potential of MERS-CoV. In line with the presence of MERS-CoV receptor in the rabbit nasal epithelium, high levels of viral RNA were shed from the nose following virus inoculation. However, unlike MERS-CoV-infected dromedaries, these rabbits did not develop clinical manifestations including nasal discharge and did shed only limited amounts of infectious virus from the nose. Consistently, no transmission by contact or airborne routes was observed in rabbits. Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission.",2019 Apr 24,"['Widagdo, W.', 'Okba, Nisreen M. A.', 'Richard, Mathilde', 'de Meulder, Dennis', 'Bestebroer, Theo M.', 'Lexmond, Pascal', 'Farag, Elmoubasher A. B. A.', 'Al-Hajri, Mohammed', 'Stittelaar, Koert J.', 'de Waal, Leon', 'van Amerongen, Geert', 'van den Brand, Judith M. A.', 'Haagmans, Bart L.', 'Herfst, Sander']",Viruses,,,True
376c6616538eb3ae465dbf8ebe62c99193ba5e42,PMC,Screening of an FDA-Approved Drug Library with a Two-Tier System Identifies an Entry Inhibitor of Severe Fever with Thrombocytopenia Syndrome Virus,http://dx.doi.org/10.3390/v11040385,PMC6520937,31027241,CC BY,"Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe disease in humans with case-fatality rates of up to 30%. There are currently very limited treatment options for SFTSV infection. We conducted a drug repurposing program by establishing a two-tier test system to rapidly screen a Food and Drug Administration- (FDA)-approved drug library for drug compounds with anti-SFTSV activity in vitro. We identified five drug compounds that inhibited SFTSV replication at low micromolar concentrations, including hexachlorophene, triclosan, regorafenib, eltrombopag, and broxyquinoline. Among them, hexachlorophene was the most potent with an IC(50) of 1.3 ± 0.3 µM and a selectivity index of 18.7. Mechanistic studies suggested that hexachlorophene was a virus entry inhibitor, which impaired SFTSV entry into host cells by interfering with cell membrane fusion. Molecular docking analysis predicted that the binding of hexachlorophene with the hydrophobic pocket between domain I and domain III of the SFTSV Gc glycoprotein was highly stable. The novel antiviral activity and mechanism of hexachlorophene in this study would facilitate the use of hexachlorophene as a lead compound to develop more entry inhibitors with higher anti-SFTSV potency and lower toxicity.",2019 Apr 25,"['Yuan, Shuofeng', 'Chan, Jasper Fuk-Woo', 'Ye, Zi-Wei', 'Wen, Lei', 'Tsang, Terance Gi-Wai', 'Cao, Jianli', 'Huang, Jingjing', 'Chan, Chris Chun-Yiu', 'Chik, Kenn Ka-Heng', 'Choi, Garnet Kwan-Yue', 'Cai, Jian-Piao', 'Yin, Feifei', 'Chu, Hin', 'Liang, Mifang', 'Jin, Dong-Yan', 'Yuen, Kwok-Yung']",Viruses,,,True
f93195034f642c748faae11cb58300881eb7b2bb,PMC,Porcine Deltacoronavirus Nucleocapsid Protein Suppressed IFN-β Production by Interfering Porcine RIG-I dsRNA-Binding and K63-Linked Polyubiquitination,http://dx.doi.org/10.3389/fimmu.2019.01024,PMC6521028,31143181,CC BY,"Porcine deltacoronavirus (PDCoV) is a newly detected porcine coronavirus causing serious vomiting and diarrhea in piglets, especially newborn piglets. There has been an outbreak of PDCoV in worldwide since 2014, causing significant economic losses in the pig industry. The interferon (IFN)-mediated antiviral response is an important component of virus-host interactions and plays an essential role in inhibiting virus infection. However, the mechanism of PDCoV escaping the porcine immune surveillance is unclear. In the present study, we demonstrated that the PDCoV nucleocapsid (N) protein antagonizes porcine IFN-β production after vesicular stomatitis virus (VSV) infection or poly(I:C) stimulation. PDCoV N protein also suppressed the activation of porcine IFN-β promoter when it was stimulated by porcine RLR signaling molecules. PDCoV N protein targeted porcine retinoic acid-inducible gene I (pRIG-I) and porcine TNF receptor associated factor 3 (pTRAF3) by directly interacting with them. The N-terminal region (1–246 aa) of PDCoV N protein was important for interacting with pRIG-I and interfere its function. We confirmed that PDCoV N antagonizes IFN-β production by associating with pRIG-I to impede it from binding double-stranded RNA. Furthermore, porcine Riplet (pRiplet) was an important activator for pRIG-I by mediating the K63-linked polyubiquitination. However, PDCoV N protein restrained the pRiplet binding pRIG-I to inhibit pRIG-I K63-linked polyubiquitination. Taken together, our results revealed a novel mechanism by which PDCoV N protein interferes with the early activation of pRIG-I in the host antiviral response. The novel findings provide a new insight into PDCoV on evading the host innate immune response and may provide new therapeutic targets and more efficacious vaccines strategies for PDCoV infections.",2019 May 9,"['Likai, Ji', 'Shasha, Li', 'Wenxian, Zhu', 'Jingjiao, Ma', 'Jianhe, Sun', 'Hengan, Wang', 'Yaxian, Yan']",Front Immunol,,,True
14b23be79f302d4603f64e7a45d56574a23b59f5,PMC,"Canine Respiratory Coronavirus, Bovine Coronavirus, and Human Coronavirus OC43: Receptors and Attachment Factors",http://dx.doi.org/10.3390/v11040328,PMC6521053,30959796,CC BY,"Despite high similarity of canine respiratory coronavirus (CRCoV), bovine coronavirus, (BCoV) and human coronavirus OC43 (HCoV-OC43), these viruses differ in species specificity. For years it was believed that they share receptor specificity, utilizing sialic acids for cell surface attachment, internalization, and entry. Interestingly, careful literature analysis shows that viruses indeed bind to the cell surface via sialic acids, but there is no solid data that these moieties mediate virus entry. In our study, using a number of techniques, we showed that all three viruses are indeed able to bind to sialic acids to a different extent, but these molecules render the cells permissive only for the clinical strain of HCoV-OC43, while for others they serve only as attachment receptors. CRCoV and BCoV appear to employ human leukocyte antigen class I (HLA-1) as the entry receptor. Furthermore, we identified heparan sulfate as an alternative attachment factor, but this may be related to the cell culture adaptation, as in ex vivo conditions, it does not seem to play a significant role. Summarizing, we delineated early events during CRCoV, BCoV, and HCoV-OC43 entry and systematically studied the attachment and entry receptor utilized by these viruses.",2019 Apr 5,"['Szczepanski, Artur', 'Owczarek, Katarzyna', 'Bzowska, Monika', 'Gula, Katarzyna', 'Drebot, Inga', 'Ochman, Marek', 'Maksym, Beata', 'Rajfur, Zenon', 'Mitchell, Judy A', 'Pyrc, Krzysztof']",Viruses,,,True
487854ccae8791d014d025e5bfec67a278f3804d,PMC,"Canine Respiratory Coronavirus, Bovine Coronavirus, and Human Coronavirus OC43: Receptors and Attachment Factors",http://dx.doi.org/10.3390/v11040328,PMC6521053,30959796,CC BY,"Despite high similarity of canine respiratory coronavirus (CRCoV), bovine coronavirus, (BCoV) and human coronavirus OC43 (HCoV-OC43), these viruses differ in species specificity. For years it was believed that they share receptor specificity, utilizing sialic acids for cell surface attachment, internalization, and entry. Interestingly, careful literature analysis shows that viruses indeed bind to the cell surface via sialic acids, but there is no solid data that these moieties mediate virus entry. In our study, using a number of techniques, we showed that all three viruses are indeed able to bind to sialic acids to a different extent, but these molecules render the cells permissive only for the clinical strain of HCoV-OC43, while for others they serve only as attachment receptors. CRCoV and BCoV appear to employ human leukocyte antigen class I (HLA-1) as the entry receptor. Furthermore, we identified heparan sulfate as an alternative attachment factor, but this may be related to the cell culture adaptation, as in ex vivo conditions, it does not seem to play a significant role. Summarizing, we delineated early events during CRCoV, BCoV, and HCoV-OC43 entry and systematically studied the attachment and entry receptor utilized by these viruses.",2019 Apr 5,"['Szczepanski, Artur', 'Owczarek, Katarzyna', 'Bzowska, Monika', 'Gula, Katarzyna', 'Drebot, Inga', 'Ochman, Marek', 'Maksym, Beata', 'Rajfur, Zenon', 'Mitchell, Judy A', 'Pyrc, Krzysztof']",Viruses,,,False
cdde042300059d2b850f850b56dc8c02d50b07e7,PMC,A Bioinformatics View of Glycan–Virus Interactions,http://dx.doi.org/10.3390/v11040374,PMC6521074,31018588,CC BY,"Evidence of the mediation of glycan molecules in the interaction between viruses and their hosts is accumulating and is now partially reflected in several online databases. Bioinformatics provides convenient and efficient means of searching, visualizing, comparing, and sometimes predicting, interactions in numerous and diverse molecular biology applications related to the -omics fields. As viromics is gaining momentum, bioinformatics support is increasingly needed. We propose a survey of the current resources for searching, visualizing, comparing, and possibly predicting host–virus interactions that integrate the presence and role of glycans. To the best of our knowledge, we have mapped the specialized and general-purpose databases with the appropriate focus. With an illustration of their potential usage, we also discuss the strong and weak points of the current bioinformatics landscape in the context of understanding viral infection and the immune response to it.",2019 Apr 23,"['Le Mercier, Philippe', 'Mariethoz, Julien', 'Lascano-Maillard, Josefina', 'Bonnardel, François', 'Imberty, Anne', 'Ricard-Blum, Sylvie', 'Lisacek, Frédérique']",Viruses,,,True
bc50818627fbe2bfdbd0b471da603d88ca9e54f4,PMC,Discovery and Characterization of Novel Bat Coronavirus Lineages from Kazakhstan,http://dx.doi.org/10.3390/v11040356,PMC6521082,30999711,CC BY,"Coronaviruses are positive-stranded RNA viruses that infect a variety of hosts, resulting in a range of symptoms from gastrointestinal illness to respiratory distress. Bats are reservoirs for a high diversity of coronaviruses, and focused surveillance detected several strains genetically similar to MERS-coronavirus, SARS-coronavirus, and the human coronaviruses 229E and NL63. The bat fauna of central Asia, which link China to eastern Europe, are relatively less studied than other regions of the world. Kazakhstan is the world’s ninth largest country; however, little is understood about the prevalence and diversity of bat-borne viruses. In this study, bat guano was collected from bat caves in three different sites of southern Kazakhstan that tested positive for coronaviruses. Our phylogenetic reconstruction indicates these are novel bat coronaviruses that belong to the genus Alphacoronavirus. In addition, two distinct lineages of Kazakhstan bat coronaviruses were detected. Both lineages are closely related to bat coronaviruses from China, France, Spain, and South Africa, suggesting that co-circulation of coronaviruses is common in multiple bat species with overlapping geographical distributions. Our study highlights the need for collaborative efforts in understudied countries to increase integrated surveillance capabilities toward better monitoring and detection of infectious diseases.",2019 Apr 17,"['Mendenhall, Ian H.', 'Kerimbayev, Aslan A.', 'Strochkov, Vitaliy M.', 'Sultankulova, Kulyaisan T.', 'Kopeyev, Syrym K.', 'Su, Yvonne C.F.', 'Smith, Gavin J.D.', 'Orynbayev, Mukhit B.']",Viruses,,,True
40cfb1f8405dcf1034654852e3729c21fcfa8f44,PMC,Discovery and Characterization of Novel Bat Coronavirus Lineages from Kazakhstan,http://dx.doi.org/10.3390/v11040356,PMC6521082,30999711,CC BY,"Coronaviruses are positive-stranded RNA viruses that infect a variety of hosts, resulting in a range of symptoms from gastrointestinal illness to respiratory distress. Bats are reservoirs for a high diversity of coronaviruses, and focused surveillance detected several strains genetically similar to MERS-coronavirus, SARS-coronavirus, and the human coronaviruses 229E and NL63. The bat fauna of central Asia, which link China to eastern Europe, are relatively less studied than other regions of the world. Kazakhstan is the world’s ninth largest country; however, little is understood about the prevalence and diversity of bat-borne viruses. In this study, bat guano was collected from bat caves in three different sites of southern Kazakhstan that tested positive for coronaviruses. Our phylogenetic reconstruction indicates these are novel bat coronaviruses that belong to the genus Alphacoronavirus. In addition, two distinct lineages of Kazakhstan bat coronaviruses were detected. Both lineages are closely related to bat coronaviruses from China, France, Spain, and South Africa, suggesting that co-circulation of coronaviruses is common in multiple bat species with overlapping geographical distributions. Our study highlights the need for collaborative efforts in understudied countries to increase integrated surveillance capabilities toward better monitoring and detection of infectious diseases.",2019 Apr 17,"['Mendenhall, Ian H.', 'Kerimbayev, Aslan A.', 'Strochkov, Vitaliy M.', 'Sultankulova, Kulyaisan T.', 'Kopeyev, Syrym K.', 'Su, Yvonne C.F.', 'Smith, Gavin J.D.', 'Orynbayev, Mukhit B.']",Viruses,,,False
40bf10143cbee94371fb682e9bf1dbfe05884433,PMC,Assessment of Immunogenicity and Neutralisation Efficacy of Viral-Vectored Vaccines Against Chikungunya Virus,http://dx.doi.org/10.3390/v11040322,PMC6521086,30987160,CC BY,"Chikungunya virus (CHIKV) has caused extensive outbreaks in several countries within the Americas, Asia, Oceanic/Pacific Islands, and Europe. In humans, CHIKV infections cause a debilitating disease with acute febrile illness and long-term polyarthralgia. Acute and chronic symptoms impose a major economic burden to health systems and contribute to poverty in affected countries. An efficacious vaccine would be an important step towards decreasing the disease burden caused by CHIKV infection. Despite no licensed vaccine is yet available for CHIKV, there is strong evidence of effective asymptomatic viral clearance due to neutralising antibodies against the viral structural proteins. We have designed viral-vectored vaccines to express the structural proteins of CHIKV, using the replication-deficient chimpanzee adenoviral platform, ChAdOx1. Expression of the CHIKV antigens results in the formation of chikungunya virus-like particles. Our vaccines induce high frequencies of anti-chikungunya specific T-cell responses as well as high titres of anti-CHIKV E2 antibodies with high capacity for in vitro neutralisation. Our results indicate the potential for further clinical development of the ChAdOx1 vaccine platform in CHIKV vaccinology.",2019 Apr 3,"['López-Camacho, César', 'Chan Kim, Young', 'Blight, Joshua', 'Lazaro Moreli, Marcos', 'Montoya-Diaz, Eduardo', 'T Huiskonen, Juha', 'Mareike Kümmerer, Beate', 'Reyes-Sandoval, Arturo']",Viruses,,,True
b2126ad45f5a952f27851ec2ef42245a3d8f09c4,PMC,Porcine Epidemic Diarrhea Virus (PEDV) ORF3 Interactome Reveals Inhibition of Virus Replication by Cellular VPS36 Protein,http://dx.doi.org/10.3390/v11040382,PMC6521123,31022991,CC BY,"The accessory protein ORF3 of porcine epidemic diarrhea virus (PEDV) has been proposed to play a key role in virus replication. However, our understanding of its function regarding virus and host interaction is still limited. In this study, we employed immunoprecipitation and mass spectrometry to screen for cellular interacting partners of ORF3. Gene ontology analysis of the host interactome highlighted the involvement of ORF3 in endosomal and immune signaling pathways. Among the identified ORF3-interacting proteins, the vacuolar protein-sorting-associated protein 36 (VPS36) was assessed for its role in PEDV replication. VPS36 was found to interact with ORF3 regardless of its GLUE domain. As a result of VPS36–ORF3 interaction, PEDV replication was substantially suppressed in cells overexpressing VPS36. Interestingly, the ORF3 protein expression was diminished in VPS36-overexpressing cells, an effect that could not be restored by treatment of lysosomal inhibitors. In addition, disruption of endogenously-expressed VPS36 by siRNA could partially augment PEDV replication. Taken together, our study provides mechanistic insights into the contribution of ORF3 in PEDV replication.",2019 Apr 24,"['Kaewborisuth, Challika', 'Yingchutrakul, Yodying', 'Roytrakul, Sittiruk', 'Jongkaewwattana, Anan']",Viruses,,,True
6d877ad702d3ec780c709976a45e6faf4e8a79b3,PMC,Porcine Epidemic Diarrhea Virus (PEDV) ORF3 Interactome Reveals Inhibition of Virus Replication by Cellular VPS36 Protein,http://dx.doi.org/10.3390/v11040382,PMC6521123,31022991,CC BY,"The accessory protein ORF3 of porcine epidemic diarrhea virus (PEDV) has been proposed to play a key role in virus replication. However, our understanding of its function regarding virus and host interaction is still limited. In this study, we employed immunoprecipitation and mass spectrometry to screen for cellular interacting partners of ORF3. Gene ontology analysis of the host interactome highlighted the involvement of ORF3 in endosomal and immune signaling pathways. Among the identified ORF3-interacting proteins, the vacuolar protein-sorting-associated protein 36 (VPS36) was assessed for its role in PEDV replication. VPS36 was found to interact with ORF3 regardless of its GLUE domain. As a result of VPS36–ORF3 interaction, PEDV replication was substantially suppressed in cells overexpressing VPS36. Interestingly, the ORF3 protein expression was diminished in VPS36-overexpressing cells, an effect that could not be restored by treatment of lysosomal inhibitors. In addition, disruption of endogenously-expressed VPS36 by siRNA could partially augment PEDV replication. Taken together, our study provides mechanistic insights into the contribution of ORF3 in PEDV replication.",2019 Apr 24,"['Kaewborisuth, Challika', 'Yingchutrakul, Yodying', 'Roytrakul, Sittiruk', 'Jongkaewwattana, Anan']",Viruses,,,False
b37857f5ea12c3dadcd0929c3c38720fc8c7d028,PMC,A Reverse Genetics System for Cypovirus Based on a Bacmid Expressing T7 RNA Polymerase,http://dx.doi.org/10.3390/v11040314,PMC6521135,30939777,CC BY,"Dendrolimus punctatus cypovirus (DpCPV), belonging to the genus Cypovirus within the family Reoviridae, is considered the most destructive pest of pine forests worldwide. DpCPV has a genome consisting of 10 linear double-stranded RNA segments. To establish a reverse genetics system, we cloned cDNAs encoding the 10 genomic segments of DpCPV into three reverse genetics vectors in which each segment was transcribed under the control of a T7 RNA polymerase promoter and terminator tagged with a hepatitis delta virus ribozyme sequence. We also constructed a vp80-knockout Autographa californica multiple nucleopolyhedrovirus bacmid to express a T7 RNA polymerase codon-optimized for Sf9 cells. Following transfection of Sf9 cells with the three vectors and the bacmid, occlusion bodies (OBs) with the typical morphology of cypovirus polyhedra were observed by optical microscopy. The rescue system was verified by incorporation of a HindIII restriction enzyme site null mutant of the 9th genomic segment. Furthermore, when we co-transfected Sf9 cells with the reverse genetics vectors, the bacmid, and an additional vector bearing an egfp gene flanked with the 5′ and 3′ untranslated regions of the 10th genomic segment, aggregated green fluorescence co-localizing with the OBs was observed. The rescued OBs were able to infect Spodopetra exigua larvae, although their infectivity was significantly lower than that of wild-type DpCPV. This reverse genetics system for DpCPV could be used to explore viral replication and pathogenesis and to facilitate the development of novel bio-insecticides and expression systems for exogenous proteins.",2019 Apr 1,"['Zhang, Gaobo', 'Yang, Jian', 'Qin, Fujun', 'Xu, Congrui', 'Wang, Jia', 'Lei, Chengfeng', 'Hu, Jia', 'Sun, Xiulian']",Viruses,,,True
89c79a5b62d264e111930b51aaecb7343b24b7a9,PMC,A Reverse Genetics System for Cypovirus Based on a Bacmid Expressing T7 RNA Polymerase,http://dx.doi.org/10.3390/v11040314,PMC6521135,30939777,CC BY,"Dendrolimus punctatus cypovirus (DpCPV), belonging to the genus Cypovirus within the family Reoviridae, is considered the most destructive pest of pine forests worldwide. DpCPV has a genome consisting of 10 linear double-stranded RNA segments. To establish a reverse genetics system, we cloned cDNAs encoding the 10 genomic segments of DpCPV into three reverse genetics vectors in which each segment was transcribed under the control of a T7 RNA polymerase promoter and terminator tagged with a hepatitis delta virus ribozyme sequence. We also constructed a vp80-knockout Autographa californica multiple nucleopolyhedrovirus bacmid to express a T7 RNA polymerase codon-optimized for Sf9 cells. Following transfection of Sf9 cells with the three vectors and the bacmid, occlusion bodies (OBs) with the typical morphology of cypovirus polyhedra were observed by optical microscopy. The rescue system was verified by incorporation of a HindIII restriction enzyme site null mutant of the 9th genomic segment. Furthermore, when we co-transfected Sf9 cells with the reverse genetics vectors, the bacmid, and an additional vector bearing an egfp gene flanked with the 5′ and 3′ untranslated regions of the 10th genomic segment, aggregated green fluorescence co-localizing with the OBs was observed. The rescued OBs were able to infect Spodopetra exigua larvae, although their infectivity was significantly lower than that of wild-type DpCPV. This reverse genetics system for DpCPV could be used to explore viral replication and pathogenesis and to facilitate the development of novel bio-insecticides and expression systems for exogenous proteins.",2019 Apr 1,"['Zhang, Gaobo', 'Yang, Jian', 'Qin, Fujun', 'Xu, Congrui', 'Wang, Jia', 'Lei, Chengfeng', 'Hu, Jia', 'Sun, Xiulian']",Viruses,,,False
ee14de143337eec0e9708f8139bfac2b7b8fdd27,PMC,Characterization of a New Member of Alphacoronavirus with Unique Genomic Features in Rhinolophus Bats,http://dx.doi.org/10.3390/v11040379,PMC6521148,31022925,CC BY,"Bats have been identified as a natural reservoir of a variety of coronaviruses (CoVs). Several of them have caused diseases in humans and domestic animals by interspecies transmission. Considering the diversity of bat coronaviruses, bat species and populations, we expect to discover more bat CoVs through virus surveillance. In this study, we described a new member of alphaCoV (BtCoV/Rh/YN2012) in bats with unique genome features. Unique accessory genes, ORF4a and ORF4b were found between the spike gene and the envelope gene, while ORF8 gene was found downstream of the nucleocapsid gene. All the putative genes were further confirmed by reverse-transcription analyses. One unique gene at the 3’ end of the BtCoV/Rh/YN2012 genome, ORF9, exhibits ~30% amino acid identity to ORF7a of the SARS-related coronavirus. Functional analysis showed ORF4a protein can activate IFN-β production, whereas ORF3a can regulate NF-κB production. We also screened the spike-mediated virus entry using the spike-pseudotyped retroviruses system, although failed to find any fully permissive cells. Our results expand the knowledge on the genetic diversity of bat coronaviruses. Continuous screening of bat viruses will help us further understand the important role played by bats in coronavirus evolution and transmission.",2019 Apr 24,"['Wang, Ning', 'Luo, Chuming', 'Liu, Haizhou', 'Yang, Xinglou', 'Hu, Ben', 'Zhang, Wei', 'Li, Bei', 'Zhu, Yan', 'Zhu, Guangjian', 'Shen, Xurui', 'Peng, Cheng', 'Shi, Zhengli']",Viruses,,,True
05a52fe28de83b331a2625473d6eabe95af62cc7,PMC,Determining the Replication Kinetics and Cellular Tropism of Influenza D Virus on Primary Well-Differentiated Human Airway Epithelial Cells,http://dx.doi.org/10.3390/v11040377,PMC6521319,31022887,CC BY,"Influenza viruses are notorious pathogens that frequently cross the species barrier with often severe consequences for both animal and human health. In 2011, a novel member of the Orthomyxoviridae family, Influenza D virus (IDV), was identified in the respiratory tract of swine. Epidemiological surveys revealed that IDV is distributed worldwide among livestock and that IDV-directed antibodies are detected in humans with occupational exposure to livestock. To identify the transmission capability of IDV to humans, we determined the viral replication kinetics and cell tropism using an in vitro respiratory epithelium model of humans. The inoculation of IDV revealed efficient replication kinetics and apical progeny virus release at different body temperatures. Intriguingly, the replication characteristics of IDV revealed higher replication kinetics compared to Influenza C virus, despite sharing the cell tropism preference for ciliated cells. Collectively, these results might indicate why IDV-directed antibodies are detected among humans with occupational exposure to livestock.",2019 Apr 24,"['Holwerda, Melle', 'Kelly, Jenna', 'Laloli, Laura', 'Stürmer, Isabel', 'Portmann, Jasmine', 'Stalder, Hanspeter', 'Dijkman, Ronald']",Viruses,,,True
d85947b143a63770afe15a194fcdc4b9375b262b,PMC,Determining the Replication Kinetics and Cellular Tropism of Influenza D Virus on Primary Well-Differentiated Human Airway Epithelial Cells,http://dx.doi.org/10.3390/v11040377,PMC6521319,31022887,CC BY,"Influenza viruses are notorious pathogens that frequently cross the species barrier with often severe consequences for both animal and human health. In 2011, a novel member of the Orthomyxoviridae family, Influenza D virus (IDV), was identified in the respiratory tract of swine. Epidemiological surveys revealed that IDV is distributed worldwide among livestock and that IDV-directed antibodies are detected in humans with occupational exposure to livestock. To identify the transmission capability of IDV to humans, we determined the viral replication kinetics and cell tropism using an in vitro respiratory epithelium model of humans. The inoculation of IDV revealed efficient replication kinetics and apical progeny virus release at different body temperatures. Intriguingly, the replication characteristics of IDV revealed higher replication kinetics compared to Influenza C virus, despite sharing the cell tropism preference for ciliated cells. Collectively, these results might indicate why IDV-directed antibodies are detected among humans with occupational exposure to livestock.",2019 Apr 24,"['Holwerda, Melle', 'Kelly, Jenna', 'Laloli, Laura', 'Stürmer, Isabel', 'Portmann, Jasmine', 'Stalder, Hanspeter', 'Dijkman, Ronald']",Viruses,,,False
960f5c1ce2c58eaa9e271f8246d3844aac1082f3,PMC,HIV-1 Envelope Glycoprotein at the Interface of Host Restriction and Virus Evasion,http://dx.doi.org/10.3390/v11040311,PMC6521621,30935048,CC BY,"Without viral envelope proteins, viruses cannot enter cells to start infection. As the major viral proteins present on the surface of virions, viral envelope proteins are a prominent target of the host immune system in preventing and ultimately eliminating viral infection. In addition to the well-appreciated adaptive immunity that produces envelope protein-specific antibodies and T cell responses, recent studies have begun to unveil a rich layer of host innate immune mechanisms restricting viral entry. This review focuses on the exciting progress that has been made in this new direction of research, by discussing various known examples of host restriction of viral entry, and diverse viral countering strategies, in particular, the emerging role of viral envelope proteins in evading host innate immune suppression. We will also highlight the effective cooperation between innate and adaptive immunity to achieve the synergistic control of viral infection by targeting viral envelope protein and checking viral escape. Given that many of the related findings were made with HIV-1, we will use HIV-1 as the model virus to illustrate the basic principles and molecular mechanisms on host restriction targeting HIV-1 envelope protein.",2019 Mar 30,"['Beitari, Saina', 'Wang, Yimeng', 'Liu, Shan-Lu', 'Liang, Chen']",Viruses,,,True
7e2cac5308e11493311bc4a3e8d15c9b9e7885ad,PMC,The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression,http://dx.doi.org/10.1371/journal.ppat.1007756,PMC6521996,31095648,CC BY,"ADP-ribosylation is a ubiquitous post-translational addition of either monomers or polymers of ADP-ribose to target proteins by ADP-ribosyltransferases, usually by interferon-inducible diphtheria toxin-like enzymes known as PARPs. While several PARPs have known antiviral activities, these activities are mostly independent of ADP-ribosylation. Consequently, less is known about the antiviral effects of ADP-ribosylation. Several viral families, including Coronaviridae, Togaviridae, and Hepeviridae, encode for macrodomain proteins that bind to and hydrolyze ADP-ribose from proteins and are critical for optimal replication and virulence. These results suggest that macrodomains counter cellular ADP-ribosylation, but whether PARPs or, alternatively, other ADP-ribosyltransferases cause this modification is not clear. Here we show that pan-PARP inhibition enhanced replication and inhibited interferon production in primary macrophages infected with macrodomain-mutant but not wild-type coronavirus. Specifically, knockdown of two abundantly expressed PARPs, PARP12 and PARP14, led to increased replication of mutant but did not significantly affect wild-type virus. PARP14 was also important for the induction of interferon in mouse and human cells, indicating a critical role for this PARP in the regulation of innate immunity. In summary, these data demonstrate that the macrodomain is required to prevent PARP-mediated inhibition of coronavirus replication and enhancement of interferon production.",2019 May 16,"['Grunewald, Matthew E.', 'Chen, Yating', 'Kuny, Chad', 'Maejima, Takashi', 'Lease, Robert', 'Ferraris, Dana', 'Aikawa, Masanori', 'Sullivan, Christopher S.', 'Perlman, Stanley', 'Fehr, Anthony R.']",PLoS Pathog,,,True
1821674721e32961f0f8c6aa3dc7c13c96b693c4,PMC,Mortality due to Cryptococcus neoformans and Cryptococcus gattii in low-income settings: an autopsy study,http://dx.doi.org/10.1038/s41598-019-43941-w,PMC6522501,31097746,CC BY,"Cryptococcosis is a major opportunistic infection and is one of the leading causes of death in adults living with HIV in sub-Saharan Africa. Recent estimates indicate that more than 130,000 people may die annually of cryptococcal meningitis in this region. Although complete diagnostic autopsy (CDA) is considered the gold standard for determining the cause of death, it is seldom performed in low income settings. In this study, a CDA was performed in 284 deceased patients from Mozambique (n = 223) and Brazil (n = 61). In depth histopathological and microbiological analyses were carried out in all cases dying of cryptococcosis. We determined the cryptococcal species, the molecular and sero-mating types and antifungal susceptibility. We also described the organs affected and reviewed the clinical presentation and patient management. Among the 284 cases included, 17 fatal cryptococcal infections were diagnosed. Cryptococcus was responsible for 16 deaths among the 163 HIV-positive patients (10%; 95%CI: 6–15%), including four maternal deaths. One third of the cases corresponded to C. gattii (VGI and VGIV molecular types, Bα and Cα strains) and the remaining infections typed were caused by C. neoformans var. Grubii (all VNI and Aα strains). The level of pre-mortem clinical suspicion was low (7/17, 41%), and 7/17 patients (41%) died within the first 72 hours of admission. Cryptococcosis was responsible for a significant proportion of AIDS-related mortality. The clinical diagnosis and patient management were inadequate, supporting the need for cryptococcal screening for early detection of the disease. This is the first report of the presence of C. gattii infection in Mozambique.",2019 May 16,"['Hurtado, Juan Carlos', 'Castillo, Paola', 'Fernandes, Fabiola', 'Navarro, Mireia', 'Lovane, Lucilia', 'Casas, Isaac', 'Quintó, Llorenç', 'Marco, Francesc', 'Jordao, Dercio', 'Ismail, Mamudo R.', 'Lorenzoni, Cesaltina', 'Martinez-Palhares, Antonio E.', 'Ferreira, Luiz', 'Lacerda, Marcus', 'Monteiro, Wuelton', 'Sanz, Ariadna', 'Letang, Emilio', 'Marimon, Lorena', 'Jesri, Susan', 'Cossa, Anelsio', 'Mandomando, Inacio', 'Vila, Jordi', 'Bassat, Quique', 'Ordi, Jaume', 'Menéndez, Clara', 'Carrilho, Carla', 'Martínez, Miguel J.']",Sci Rep,,,True
b425f0738b20e099ee04f992b86fe35e827acedf,PMC,Association between genetic polymorphisms and osteonecrosis in steroid treatment populations: a detailed stratified and dose-response meta-analysis,http://dx.doi.org/10.1042/BSR20190024,PMC6522878,30996113,CC BY,"Steroid treatment has become recognized as an important risk factor for avascular osteonecrosis of the femoral head. However, not all patients who receive long-term, high-dose steroids develop osteonecrosis, indicating that there are individual differences in occurrence. We explored the relationship between polymorphisms and steroid-induced osteonecrosis of the femoral head (SONFH) incidence with variables. We used a multilevel mixed-effects logistic regression model, which is an expansion of logistic regression, for each type of steroid, primary disease, drug dose, applied duration, and single-nucleotide polymorphism (SNP). We also conducted a dose-response meta-analysis to analyze the cumulative dosage and SONFH risk in mutation carriers. There were significant correlations between the ABCB1 rs1045642 mutant and SONFH in the prednisone-use and methylprednisolone/prednisone-use populations. The ABCB1 rs2032582 mutant homozygote had a protective effect in the methylprednisolone/prednisolone renal transplant population. For ApoB rs693, mutation increased the incidence of SONFH in prednisone-use and methylprednisolone/prednisolone-use populations and renal transplant patients. For ApoB rs1042031, mutation increased the risk of SONFH in the prednisone-use population. The PAI-1 rs1799768 mutation had a protective effect on the SONFH risk prednisone-use and renal transplant populations. ABCB1 rs1045642 mutations have a protective effect against SONFH, and ApoB rs693 and rs1042031 increase the SONFH risk. Cumulative dosage and treatment duration had little effect on the results. In addition, there was a dose-effect correlation in ABCB1 rs1045642 and rs2032582 mutation carriers.",2019 May 14,"['Yang, Jun', 'Jing, Ming', 'Yang, Xiaoge']",Biosci Rep,,,False
0597b458ac250cffe02827f4448a2bfd4e5e05f3,PMC,Association between genetic polymorphisms and osteonecrosis in steroid treatment populations: a detailed stratified and dose-response meta-analysis,http://dx.doi.org/10.1042/BSR20190024,PMC6522878,30996113,CC BY,"Steroid treatment has become recognized as an important risk factor for avascular osteonecrosis of the femoral head. However, not all patients who receive long-term, high-dose steroids develop osteonecrosis, indicating that there are individual differences in occurrence. We explored the relationship between polymorphisms and steroid-induced osteonecrosis of the femoral head (SONFH) incidence with variables. We used a multilevel mixed-effects logistic regression model, which is an expansion of logistic regression, for each type of steroid, primary disease, drug dose, applied duration, and single-nucleotide polymorphism (SNP). We also conducted a dose-response meta-analysis to analyze the cumulative dosage and SONFH risk in mutation carriers. There were significant correlations between the ABCB1 rs1045642 mutant and SONFH in the prednisone-use and methylprednisolone/prednisone-use populations. The ABCB1 rs2032582 mutant homozygote had a protective effect in the methylprednisolone/prednisolone renal transplant population. For ApoB rs693, mutation increased the incidence of SONFH in prednisone-use and methylprednisolone/prednisolone-use populations and renal transplant patients. For ApoB rs1042031, mutation increased the risk of SONFH in the prednisone-use population. The PAI-1 rs1799768 mutation had a protective effect on the SONFH risk prednisone-use and renal transplant populations. ABCB1 rs1045642 mutations have a protective effect against SONFH, and ApoB rs693 and rs1042031 increase the SONFH risk. Cumulative dosage and treatment duration had little effect on the results. In addition, there was a dose-effect correlation in ABCB1 rs1045642 and rs2032582 mutation carriers.",2019 May 14,"['Yang, Jun', 'Jing, Ming', 'Yang, Xiaoge']",Biosci Rep,,,True
f29135f51da3a6598b511bad1514be9195bf1624,PMC,miR-1306 Mediates the Feedback Regulation of the TGF-β/SMAD Signaling Pathway in Granulosa Cells,http://dx.doi.org/10.3390/cells8040298,PMC6523565,30935128,CC BY,"Transforming growth factor-β receptor II (TGFBR2), the type II receptor of the TGF-β/SMA- and MAD-related protein (SMAD) signaling pathway, plays a crucial role in TGF-β signal transduction and is regulated by multiple factors. Nevertheless, the modulation of the non-coding RNA involved in the process of TGFBR2 expression in ovaries is not well studied. In our study, we isolated and characterized the 3′-untranslated region (UTR) of the porcine TGFBR2 gene and microRNA-1306 (miR-1306) was identified as the functional miRNA that targets TGFBR2 in porcine granulosa cells (GCs). Functional analysis showed that miR-1306 promotes apoptosis of GCs as well as attenuating the TGF-β/SMAD signaling pathway targeting and impairing TGFBR2 in GCs. Moreover, we identified the miR-1306 core promoter and found three potential SMAD4-binding elements (SBEs). Luciferase and chromatin immunoprecipitation (ChIP) assays revealed that the transcription factor SMAD4 directly binds to the miR-1306 core promoter and inhibits its transcriptional activity. Furthermore, the TGF-β/SMAD signaling pathway is modulated by SMAD4 positive feedback via inhibition of miR-1306 expression in GCs. Collectively, our findings provide evidence of an epigenetic mechanism that modulates as well as mediates the feedback regulation of the classical TGF-β/SMAD signaling pathway in GCs from porcine ovaries.",2019 Mar 31,"['Yang, Liu', 'Du, Xing', 'Liu, Lu', 'Cao, Qiuyu', 'Pan, Zengxiang', 'Li, Qifa']",Cells,,,True
34b8edf90b257de03bb8a408b8fc58544b479d4c,PMC,Harnessed viruses in the age of metagenomics and synthetic biology: an update on infectious clone assembly and biotechnologies of plant viruses,http://dx.doi.org/10.1111/pbi.13084,PMC6523588,30677208,CC BY,"Recent metagenomic studies have provided an unprecedented wealth of data, which are revolutionizing our understanding of virus diversity. A redrawn landscape highlights viruses as active players in the phytobiome, and surveys have uncovered their positive roles in environmental stress tolerance of plants. Viral infectious clones are key tools for functional characterization of known and newly identified viruses. Knowledge of viruses and their components has been instrumental for the development of modern plant molecular biology and biotechnology. In this review, we provide extensive guidelines built on current synthetic biology advances that streamline infectious clone assembly, thus lessening a major technical constraint of plant virology. The focus is on generation of infectious clones in binary T‐DNA vectors, which are delivered efficiently to plants by Agrobacterium. We then summarize recent applications of plant viruses and explore emerging trends in microbiology, bacterial and human virology that, once translated to plant virology, could lead to the development of virus‐based gene therapies for ad hoc engineering of plant traits. The systematic characterization of plant virus roles in the phytobiome and next‐generation virus‐based tools will be indispensable landmarks in the synthetic biology roadmap to better crops.",2019 Jun 28,"['Pasin, Fabio', 'Menzel, Wulf', 'Daròs, José‐Antonio']",Plant Biotechnol J,,,True
50f9ea2210efc3c98630da060b4254036f83c516,PMC,Secretory Nanoparticles of Neospora caninum Profilin-Fused with the Transmembrane Domain of GP64 from Silkworm Hemolymph,http://dx.doi.org/10.3390/nano9040593,PMC6523865,30974883,CC BY,"Neosporosis, which is caused by Neospora caninum, is a well-known disease in the veterinary field. Infections in pregnant cattle lead to abortion via transplacental (congenitally from mother to fetus) transmission. In this study, a N. caninum profilin (NcPROF), was expressed in silkworm larvae by recombinant Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid and was purified from the hemolymph. Three NcPROF constructs were investigated, native NcPROF fused with an N-terminal PA tag (PA-NcPROF), PA-NcPROF fused with the signal sequence of bombyxin from B. mori (bx-PA-NcPROF), and bx-PA-NcPROF with additional C-terminal transmembrane and cytoplasmic domains of GP64 from BmNPV (bx-PA-NcPROF-GP64TM). All recombinant proteins were observed extra- and intracellularly in cultured Bm5 cells and silkworm larvae. The bx-PA-NcPROF-GP64TM was partly abnormally secreted, even though it has the transmembrane domain, and only it was pelleted by ultracentrifugation, but PA-NcPROF and bx-PA-NcPROF were not. Additionally, bx-PA-NcPROF-GP64TM was successfully purified from silkworm hemolymph by anti-PA agarose beads while PA-NcPROF and bx-PA-NcPROF were not. The purified bx-PA-NcPROF-GP64TM protein bound to its receptor, mouse Toll-like receptor 11 (TLR-11), and formed unique nanoparticles. These results suggest that profilin fused with GP64TM was secreted as a nanoparticle with binding affinity to its receptor and this nanoparticle formation is advantageous for the development of vaccines to N. caninum.",2019 Apr 10,"['Suhaimi, Hamizah', 'Hiramatsu, Rikito', 'Xu, Jian', 'Kato, Tatsuya', 'Park, Enoch Y.']",Nanomaterials (Basel),,,True
f821a2734815ac4960cbf28aead3175f2f61aec3,PMC,Secretory Nanoparticles of Neospora caninum Profilin-Fused with the Transmembrane Domain of GP64 from Silkworm Hemolymph,http://dx.doi.org/10.3390/nano9040593,PMC6523865,30974883,CC BY,"Neosporosis, which is caused by Neospora caninum, is a well-known disease in the veterinary field. Infections in pregnant cattle lead to abortion via transplacental (congenitally from mother to fetus) transmission. In this study, a N. caninum profilin (NcPROF), was expressed in silkworm larvae by recombinant Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid and was purified from the hemolymph. Three NcPROF constructs were investigated, native NcPROF fused with an N-terminal PA tag (PA-NcPROF), PA-NcPROF fused with the signal sequence of bombyxin from B. mori (bx-PA-NcPROF), and bx-PA-NcPROF with additional C-terminal transmembrane and cytoplasmic domains of GP64 from BmNPV (bx-PA-NcPROF-GP64TM). All recombinant proteins were observed extra- and intracellularly in cultured Bm5 cells and silkworm larvae. The bx-PA-NcPROF-GP64TM was partly abnormally secreted, even though it has the transmembrane domain, and only it was pelleted by ultracentrifugation, but PA-NcPROF and bx-PA-NcPROF were not. Additionally, bx-PA-NcPROF-GP64TM was successfully purified from silkworm hemolymph by anti-PA agarose beads while PA-NcPROF and bx-PA-NcPROF were not. The purified bx-PA-NcPROF-GP64TM protein bound to its receptor, mouse Toll-like receptor 11 (TLR-11), and formed unique nanoparticles. These results suggest that profilin fused with GP64TM was secreted as a nanoparticle with binding affinity to its receptor and this nanoparticle formation is advantageous for the development of vaccines to N. caninum.",2019 Apr 10,"['Suhaimi, Hamizah', 'Hiramatsu, Rikito', 'Xu, Jian', 'Kato, Tatsuya', 'Park, Enoch Y.']",Nanomaterials (Basel),,,False
98e6190d06a8d8774c690be39634a1d64a926dc3,PMC,Genetic Diversity and Differentiation at Structurally Varying MHC Haplotypes and Microsatellites in Bottlenecked Populations of Endangered Crested Ibis,http://dx.doi.org/10.3390/cells8040377,PMC6523929,31027280,CC BY,"Investigating adaptive potential and understanding the relative roles of selection and genetic drift in populations of endangered species are essential in conservation. Major histocompatibility complex (MHC) genes characterized by spectacular polymorphism and fitness association have become valuable adaptive markers. Herein we investigate the variation of all MHC class I and II genes across seven populations of an endangered bird, the crested ibis, of which all current individuals are offspring of only two pairs. We inferred seven multilocus haplotypes from linked alleles in the Core Region and revealed structural variation of the class II region that probably evolved through unequal crossing over. Based on the low polymorphism, structural variation, strong linkage, and extensive shared alleles, we applied the MHC haplotypes in population analysis. The genetic variation and population structure at MHC haplotypes are generally concordant with those expected from microsatellites, underlining the predominant role of genetic drift in shaping MHC variation in the bottlenecked populations. Nonetheless, some populations showed elevated differentiation at MHC, probably due to limited gene flow. The seven populations were significantly differentiated into three groups and some groups exhibited genetic monomorphism, which can be attributed to founder effects. We therefore propose various strategies for future conservation and management.",2019 Apr 25,"['Lan, Hong', 'Zhou, Tong', 'Wan, Qiu-Hong', 'Fang, Sheng-Guo']",Cells,,,True
e09ca57e55d73869520543f456019ee081d88a00,PMC,Vaccination With a Single Consensus Envelope Protein Ectodomain Sequence Administered in a Heterologous Regimen Induces Tetravalent Immune Responses and Protection Against Dengue Viruses in Mice,http://dx.doi.org/10.3389/fmicb.2019.01113,PMC6524413,31134046,CC BY,"The development of a safe and effective tetravalent dengue vaccine that elicits protection against all dengue virus (DENV) serotypes is urgently needed. The consensus sequence of the ectodomain of envelope (E) protein of DENV (cE80) has been examined as an immunogen previously. In the current study, a cE80 DNA (D) vaccine was constructed and evaluated in conjunction with the cE80 protein (P) vaccine to examine whether both vaccines used together can further improve the immune responses. The cE80 DNA vaccine was administrated using either a homologous (DNA alone, DDD) or heterologous (DNA prime-protein boost: DDP or DPP) regimen, and evaluated for immunogenicity and protective efficacy in mice. Among the three DNA-based immunization regimens tested, DDP immunization is the optimal immunization regimen that elicited the greatest systemic immune response and conferred protection against all four DENV serotypes. This work provides innovative ideas for the development of consensus E-based dengue vaccines and the testing of optimal immunization regimens.",2019 May 10,"['Wang, Ran', 'Zheng, Xiaoyan', 'Sun, Jin', 'Feng, Kaihao', 'Gao, Na', 'Fan, Dongying', 'Chen, Hui', 'Jin, Xia', 'An, Jing']",Front Microbiol,,,True
7a8b68779090a6be24461fb2b19c974232899889,PMC,Structural comparison strengthens the higher-order classification of proteases related to chymotrypsin,http://dx.doi.org/10.1371/journal.pone.0216659,PMC6524800,31100077,CC BY,"Specific cleavage of proteins by proteases is essential for several cellular, physiological, and viral processes. Chymotrypsin-related proteases that form the PA clan in the MEROPS classification of proteases is one of the largest and most diverse group of proteases. The PA clan comprises serine proteases from bacteria, eukaryotes, archaea, and viruses and chymotrypsin-related cysteine proteases from positive-strand RNA viruses. Despite low amino acid sequence identity, all PA clan proteases share a conserved double β-barrel structure. Using an automated structure-based hierarchical clustering method, we identified a common structural core of 72 amino acid residues for 143 PA clan proteases that represent 12 protein families and 11 subfamilies. The identified core is located around the catalytic site between the two β-barrels and resembles the structures of the smallest PA clan proteases. We constructed a structure-based distance tree derived from the properties of the identified common core. Our structure-based analyses support the current classification of these proteases at the subfamily level and largely at the family level. Structural alignment and structure-based distance trees could thus be used for directing objective classification of PA clan proteases and to strengthen their higher order classification. Our results also indicate that the PA clan proteases of positive-strand RNA viruses are related to cellular heat-shock proteases, which suggests that the exchange of protease genes between viruses and cells might have occurred more than once.",2019 May 17,"['Mönttinen, Heli A. M.', 'Ravantti, Janne J.', 'Poranen, Minna M.']",PLoS One,,,True
c27d847f4a83abd163a1f46c8264ae1b60320501,PMC,Structural comparison strengthens the higher-order classification of proteases related to chymotrypsin,http://dx.doi.org/10.1371/journal.pone.0216659,PMC6524800,31100077,CC BY,"Specific cleavage of proteins by proteases is essential for several cellular, physiological, and viral processes. Chymotrypsin-related proteases that form the PA clan in the MEROPS classification of proteases is one of the largest and most diverse group of proteases. The PA clan comprises serine proteases from bacteria, eukaryotes, archaea, and viruses and chymotrypsin-related cysteine proteases from positive-strand RNA viruses. Despite low amino acid sequence identity, all PA clan proteases share a conserved double β-barrel structure. Using an automated structure-based hierarchical clustering method, we identified a common structural core of 72 amino acid residues for 143 PA clan proteases that represent 12 protein families and 11 subfamilies. The identified core is located around the catalytic site between the two β-barrels and resembles the structures of the smallest PA clan proteases. We constructed a structure-based distance tree derived from the properties of the identified common core. Our structure-based analyses support the current classification of these proteases at the subfamily level and largely at the family level. Structural alignment and structure-based distance trees could thus be used for directing objective classification of PA clan proteases and to strengthen their higher order classification. Our results also indicate that the PA clan proteases of positive-strand RNA viruses are related to cellular heat-shock proteases, which suggests that the exchange of protease genes between viruses and cells might have occurred more than once.",2019 May 17,"['Mönttinen, Heli A. M.', 'Ravantti, Janne J.', 'Poranen, Minna M.']",PLoS One,,,False
d1ce5f10590c8e7d0e347afd63d4f7e60e61aa3f,PMC,Structural comparison strengthens the higher-order classification of proteases related to chymotrypsin,http://dx.doi.org/10.1371/journal.pone.0216659,PMC6524800,31100077,CC BY,"Specific cleavage of proteins by proteases is essential for several cellular, physiological, and viral processes. Chymotrypsin-related proteases that form the PA clan in the MEROPS classification of proteases is one of the largest and most diverse group of proteases. The PA clan comprises serine proteases from bacteria, eukaryotes, archaea, and viruses and chymotrypsin-related cysteine proteases from positive-strand RNA viruses. Despite low amino acid sequence identity, all PA clan proteases share a conserved double β-barrel structure. Using an automated structure-based hierarchical clustering method, we identified a common structural core of 72 amino acid residues for 143 PA clan proteases that represent 12 protein families and 11 subfamilies. The identified core is located around the catalytic site between the two β-barrels and resembles the structures of the smallest PA clan proteases. We constructed a structure-based distance tree derived from the properties of the identified common core. Our structure-based analyses support the current classification of these proteases at the subfamily level and largely at the family level. Structural alignment and structure-based distance trees could thus be used for directing objective classification of PA clan proteases and to strengthen their higher order classification. Our results also indicate that the PA clan proteases of positive-strand RNA viruses are related to cellular heat-shock proteases, which suggests that the exchange of protease genes between viruses and cells might have occurred more than once.",2019 May 17,"['Mönttinen, Heli A. M.', 'Ravantti, Janne J.', 'Poranen, Minna M.']",PLoS One,,,False
b2b9b8bf44842883d2728864e2f39d2a3584e7d5,PMC,Structural comparison strengthens the higher-order classification of proteases related to chymotrypsin,http://dx.doi.org/10.1371/journal.pone.0216659,PMC6524800,31100077,CC BY,"Specific cleavage of proteins by proteases is essential for several cellular, physiological, and viral processes. Chymotrypsin-related proteases that form the PA clan in the MEROPS classification of proteases is one of the largest and most diverse group of proteases. The PA clan comprises serine proteases from bacteria, eukaryotes, archaea, and viruses and chymotrypsin-related cysteine proteases from positive-strand RNA viruses. Despite low amino acid sequence identity, all PA clan proteases share a conserved double β-barrel structure. Using an automated structure-based hierarchical clustering method, we identified a common structural core of 72 amino acid residues for 143 PA clan proteases that represent 12 protein families and 11 subfamilies. The identified core is located around the catalytic site between the two β-barrels and resembles the structures of the smallest PA clan proteases. We constructed a structure-based distance tree derived from the properties of the identified common core. Our structure-based analyses support the current classification of these proteases at the subfamily level and largely at the family level. Structural alignment and structure-based distance trees could thus be used for directing objective classification of PA clan proteases and to strengthen their higher order classification. Our results also indicate that the PA clan proteases of positive-strand RNA viruses are related to cellular heat-shock proteases, which suggests that the exchange of protease genes between viruses and cells might have occurred more than once.",2019 May 17,"['Mönttinen, Heli A. M.', 'Ravantti, Janne J.', 'Poranen, Minna M.']",PLoS One,,,False
157f0ea863d7621359dfba915c832f4cce27049a,PMC,Airway response to respiratory syncytial virus has incidental antibacterial effects,http://dx.doi.org/10.1038/s41467-019-10222-z,PMC6525170,31101811,CC BY,"RSV infection is typically associated with secondary bacterial infection. We hypothesise that the local airway immune response to RSV has incidental antibacterial effects. Using coordinated proteomics and metagenomics analysis we simultaneously analysed the microbiota and proteomes of the upper airway and determined direct antibacterial activity in airway secretions of RSV-infected children. Here, we report that the airway abundance of Streptococcus was higher in samples collected at the time of RSV infection compared with samples collected one month later. RSV infection is associated with neutrophil influx into the airway and degranulation and is marked by overexpression of proteins with known antibacterial activity including BPI, EPX, MPO and AZU1. Airway secretions of children infected with RSV, have significantly greater antibacterial activity compared to RSV-negative controls. This RSV-associated, neutrophil-mediated antibacterial response in the airway appears to act as a regulatory mechanism that modulates bacterial growth in the airways of RSV-infected children.",2019 May 17,"['Sande, Charles J.', 'Njunge, James M.', 'Mwongeli Ngoi, Joyce', 'Mutunga, Martin N.', 'Chege, Timothy', 'Gicheru, Elijah T.', 'Gardiner, Elizabeth M.', 'Gwela, Agnes', 'Green, Christopher A.', 'Drysdale, Simon B.', 'Berkley, James A.', 'Nokes, D. James', 'Pollard, Andrew J.']",Nat Commun,,,False
b1c01e51053266154ff1cf59628c2cb92a8184ba,PMC,Airway response to respiratory syncytial virus has incidental antibacterial effects,http://dx.doi.org/10.1038/s41467-019-10222-z,PMC6525170,31101811,CC BY,"RSV infection is typically associated with secondary bacterial infection. We hypothesise that the local airway immune response to RSV has incidental antibacterial effects. Using coordinated proteomics and metagenomics analysis we simultaneously analysed the microbiota and proteomes of the upper airway and determined direct antibacterial activity in airway secretions of RSV-infected children. Here, we report that the airway abundance of Streptococcus was higher in samples collected at the time of RSV infection compared with samples collected one month later. RSV infection is associated with neutrophil influx into the airway and degranulation and is marked by overexpression of proteins with known antibacterial activity including BPI, EPX, MPO and AZU1. Airway secretions of children infected with RSV, have significantly greater antibacterial activity compared to RSV-negative controls. This RSV-associated, neutrophil-mediated antibacterial response in the airway appears to act as a regulatory mechanism that modulates bacterial growth in the airways of RSV-infected children.",2019 May 17,"['Sande, Charles J.', 'Njunge, James M.', 'Mwongeli Ngoi, Joyce', 'Mutunga, Martin N.', 'Chege, Timothy', 'Gicheru, Elijah T.', 'Gardiner, Elizabeth M.', 'Gwela, Agnes', 'Green, Christopher A.', 'Drysdale, Simon B.', 'Berkley, James A.', 'Nokes, D. James', 'Pollard, Andrew J.']",Nat Commun,,,True
e09bbfaf70862c6831f0ea21f420baaa0194cd46,PMC,Airway response to respiratory syncytial virus has incidental antibacterial effects,http://dx.doi.org/10.1038/s41467-019-10222-z,PMC6525170,31101811,CC BY,"RSV infection is typically associated with secondary bacterial infection. We hypothesise that the local airway immune response to RSV has incidental antibacterial effects. Using coordinated proteomics and metagenomics analysis we simultaneously analysed the microbiota and proteomes of the upper airway and determined direct antibacterial activity in airway secretions of RSV-infected children. Here, we report that the airway abundance of Streptococcus was higher in samples collected at the time of RSV infection compared with samples collected one month later. RSV infection is associated with neutrophil influx into the airway and degranulation and is marked by overexpression of proteins with known antibacterial activity including BPI, EPX, MPO and AZU1. Airway secretions of children infected with RSV, have significantly greater antibacterial activity compared to RSV-negative controls. This RSV-associated, neutrophil-mediated antibacterial response in the airway appears to act as a regulatory mechanism that modulates bacterial growth in the airways of RSV-infected children.",2019 May 17,"['Sande, Charles J.', 'Njunge, James M.', 'Mwongeli Ngoi, Joyce', 'Mutunga, Martin N.', 'Chege, Timothy', 'Gicheru, Elijah T.', 'Gardiner, Elizabeth M.', 'Gwela, Agnes', 'Green, Christopher A.', 'Drysdale, Simon B.', 'Berkley, James A.', 'Nokes, D. James', 'Pollard, Andrew J.']",Nat Commun,,,False
bf2fca4f15e9e4d36ab0e8a8c2b5b8c4b1009c04,PMC,Airway response to respiratory syncytial virus has incidental antibacterial effects,http://dx.doi.org/10.1038/s41467-019-10222-z,PMC6525170,31101811,CC BY,"RSV infection is typically associated with secondary bacterial infection. We hypothesise that the local airway immune response to RSV has incidental antibacterial effects. Using coordinated proteomics and metagenomics analysis we simultaneously analysed the microbiota and proteomes of the upper airway and determined direct antibacterial activity in airway secretions of RSV-infected children. Here, we report that the airway abundance of Streptococcus was higher in samples collected at the time of RSV infection compared with samples collected one month later. RSV infection is associated with neutrophil influx into the airway and degranulation and is marked by overexpression of proteins with known antibacterial activity including BPI, EPX, MPO and AZU1. Airway secretions of children infected with RSV, have significantly greater antibacterial activity compared to RSV-negative controls. This RSV-associated, neutrophil-mediated antibacterial response in the airway appears to act as a regulatory mechanism that modulates bacterial growth in the airways of RSV-infected children.",2019 May 17,"['Sande, Charles J.', 'Njunge, James M.', 'Mwongeli Ngoi, Joyce', 'Mutunga, Martin N.', 'Chege, Timothy', 'Gicheru, Elijah T.', 'Gardiner, Elizabeth M.', 'Gwela, Agnes', 'Green, Christopher A.', 'Drysdale, Simon B.', 'Berkley, James A.', 'Nokes, D. James', 'Pollard, Andrew J.']",Nat Commun,,,True
fc3262c27f701261cfc1b27bc0495f6bd8b3e3fd,PMC,Function of the RNA Coliphage Qβ Proteins in Medical In Vitro Evolution,http://dx.doi.org/10.3390/mps1020018,PMC6526423,31164561,CC BY,"Qβ is a positive (+) single-stranded RNA bacteriophage covered by a 25 nm icosahedral shell. Qβ belongs to the family of Leviviridae and is found throughout the world (bacterial isolates and sewage). The genome of Qβ is about 4.2 kb, coding for four proteins. This genome is surrounded by 180 copies of coat proteins (capsomers) each comprised of 132 residues of amino acids. The other proteins, the subunit II (β) of a replicase, the maturation protein (A(2)) and the read-through or minor coat protein (A(1)), play a key role in phage infection. With the replicase protein, which lacks proofreading activity, as well as its short replication time, and high population size, Qβ phage has attractive features for in vitro evolution. The A(1) protein gene shares the same initiation codon with the coat protein gene and is produced during translation when the coat protein’s UGA stop codon triplet (about 400 nucleotides from the initiation) is suppressed by a low level of ribosome misincorporation of tryptophan. Thus, A(1) is termed the read-through protein. This RNA phage platform technology not only serves to display foreign peptides but is also exceptionally suited to address questions about in vitro evolution. The C-terminus of A(1) protein confers to this RNA phage platform an exceptional feature of not only a linker for foreign peptide to be displayed also a model for evolution. This platform was used to present a peptide library of the G-H loop of the capsid region P1 of the foot-and-mouth disease virus (FMDV) called VP1 protein. The library was exposed on the exterior surface of Qβ phages, evolved and selected with the monoclonal antibodies (mAbs) SD6 of the FMDV. These hybrid phages could principally be good candidates for FMDV vaccine development. Separately, the membrane proximal external region (MPER) of human immunodeficiency virus type 1 (HIV-1) epitopes was fused with the A(1) proteins and exposed on the Qβ phage exterior surface. The engineered phages with MPER epitopes were recognized by anti-MPER specific antibodies. This system could be used to overcome the challenge of effective presentation of MPER to the immune system. A key portion of this linear epitope could be randomized and evolved with the Qβ system. Overall, antigens and epitopes of RNA viruses relevant to public health can be randomized, evolved and selected in pools using the proposed Qβ model to overcome their plasticity and the challenge of vaccine development. Major epitopes of a particular virus can be engineered or displayed on the Qβ phage surface and used for vaccine efficacy evaluation, thus avoiding the use of live viruses.",2018 May 31,"['Singleton, Rana L.', 'Sanders, Carrie A.', 'Jones, Kevin', 'Thorington, Bobby', 'Egbo, Timothy', 'Coats, Mamie T.', 'Waffo, Alain Bopda']",Methods Protoc,,,True
d7a470f0dbe60172ed2a21ce65b9903b4825e3a3,PMC,Paramyxovirus Infections in Ex Vivo Lung Slice Cultures of Different Host Species,http://dx.doi.org/10.3390/mps1020012,PMC6526457,31164557,CC BY,"In vivo experiments in animal models of disease are of crucial importance for viral tropism and pathogenesis studies. However, these experiments must be complemented with in vitro and ex vivo experiments. Here, we describe a protocol for the preparation and ex vivo infection of lung slices from different mammalian host species with various respiratory paramyxoviruses expressing fluorescent reporter proteins, and suggest follow-up experiments including immunohistochemistry, flow cytometry and confocal microscopy.",2018 Mar 27,"['de Vries, Rory D.', 'Rennick, Linda J.', 'Duprex, W. Paul', 'de Swart, Rik L.']",Methods Protoc,,,True
085522850a68603e453f67deacac2be1293a483f,PMC,"A computational method for the identification of Dengue, Zika and Chikungunya virus species and genotypes",http://dx.doi.org/10.1371/journal.pntd.0007231,PMC6527240,31067235,CC BY,"In recent years, an increasing number of outbreaks of Dengue, Chikungunya and Zika viruses have been reported in Asia and the Americas. Monitoring virus genotype diversity is crucial to understand the emergence and spread of outbreaks, both aspects that are vital to develop effective prevention and treatment strategies. Hence, we developed an efficient method to classify virus sequences with respect to their species and sub-species (i.e. serotype and/or genotype). This tool provides an easy-to-use software implementation of this new method and was validated on a large dataset assessing the classification performance with respect to whole-genome sequences and partial-genome sequences. Available online: http://krisp.org.za/tools.php.",2019 May 8,"['Fonseca, Vagner', 'Libin, Pieter J. K.', 'Theys, Kristof', 'Faria, Nuno R.', 'Nunes, Marcio R. T.', 'Restovic, Maria I.', 'Freire, Murilo', 'Giovanetti, Marta', 'Cuypers, Lize', 'Nowé, Ann', 'Abecasis, Ana', 'Deforche, Koen', 'Santiago, Gilberto A.', 'de Siqueira, Isadora C.', 'San, Emmanuel J.', 'Machado, Kaliane C. B.', 'Azevedo, Vasco', 'Filippis, Ana Maria Bispo-de', 'da Cunha, Rivaldo Venâncio', 'Pybus, Oliver G.', 'Vandamme, Anne-Mieke', 'Alcantara, Luiz C. J.', 'de Oliveira, Tulio']",PLoS Negl Trop Dis,,,True
62e4e3bb07c0d49b928f9cfb46d2efedc04991dd,PMC,DNA Vaccines Against Mycoplasma Elicit Humoral Immune Responses in Ostriches,http://dx.doi.org/10.3389/fimmu.2019.01061,PMC6527592,31139188,CC BY,"In ostriches, the population densities resulting from intensive rearing increases susceptibility to pathogens such as mycoplasmas. In addition to good management practices, vaccination offers an attractive alternative for controlling mycoplasma infections in food animals, instead of using antibiotics, which often leave unacceptable residues. The use of live attenuated vaccines, however, carry the concern of reversion to virulence or genetic recombination with field strains. Currently there are no commercially available vaccines against ostrich-infecting mycoplasmas and this study therefore set out to develop and evaluate the use of a DNA vaccine against mycoplasma infections in ostriches using an OppA protein as antigen. To this end, the oppA gene of “Mycoplasma nasistruthionis sp. nov.” str. Ms03 was cloned into two DNA vaccine expression vectors after codon correction by site-directed mutagenesis. Three-months-old ostriches were then vaccinated intramuscularly at different doses followed by a booster vaccination after 6 weeks. The ability of the DNA vaccines to elicit an anti-OppA antibody response was evaluated by ELISA using the recombinant OppA protein of Ms03 as coating antigen. A statistically significant anti-OppA antibody response could be detected after administration of a booster vaccination indicating that the OppA protein was successfully immunogenic. The responses were also both dose and vector dependent. In conclusion, the DNA vaccines were able to elicit an immune response in ostriches and can therefore be viewed as an option for the development of vaccines against mycoplasma infections.",2019 May 14,"['Wium, Martha', 'Jonker, Hester Isabella', 'Olivier, Adriaan Jacobus', 'Bellstedt, Dirk Uwe', 'Botes, Annelise']",Front Immunol,,,True
18af7af31b2733b2edb0b6caaf7461bfebb67cec,PMC,Epidemiology of respiratory viral infections in people with acute respiratory tract infections in Africa: the VARIAFRICA systematic review and meta-analysis protocol,http://dx.doi.org/10.1186/s13643-019-1037-1,PMC6528219,31109367,CC BY,"INTRODUCTION: Better characterisation of the epidemiological data on respiratory viral infections among people with acute respiratory tract infection (ARTI) can help to implement efficient strategies to curb the burden of ARTI in Africa. We will conduct a systematic review and meta-analysis to determine the prevalence and factors associated with respiratory viral infection in people of all ages with ARTI residing in Africa. METHODS: This work will include cross-sectional studies published between January 1, 2000 and December 31, 2017, without any language restriction, on populations residing in African countries. We will consider studies that reported the prevalence of respiratory viruses in people with ARTI confirmed by a polymerase chain reaction technique. We will be searching PubMed, Embase, African Journals Online, Web of Science, and Global Index Medicus. The selection of relevant studies, extraction of data, and evaluation of the quality of the articles will be carried out independently by two review authors, and the discrepancies will be resolved by consensus or intervention of a third author. The heterogeneity of the studies will be assessed using the χ(2) test on Cochrane’s Q statistic. Publication bias will be assessed by the Egger test. Studies will be pooled using a random-effect meta-analysis model. Results will be presented by age group and sub-region of Africa. Using meta-regression models, we will identify factors associated with viral infections in people with ARTI. DISCUSSION: This systematic review and meta-analysis is based on published data and therefore does not require ethical approval. This work will serve as a basis for the development of strategies for prevention and control ARTI in Africa and will also serve to identify data gaps and guide future investigations. The final report will be published in peer-reviewed journals as a scientific article and presented in workshops, conferences, and scientific conferences. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018088261. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13643-019-1037-1) contains supplementary material, which is available to authorized users.",2019 May 20,"['Kenmoe, Sebastien', 'Bigna, Jean Joel', 'Modiyinji, Abdou Fatawou', 'Simo, Fredy Brice N.', 'Njouom, Richard']",Syst Rev,,,False
abe4bb8686c92a65861b5738de73b4096332f2e0,PMC,Epidemiology of respiratory viral infections in people with acute respiratory tract infections in Africa: the VARIAFRICA systematic review and meta-analysis protocol,http://dx.doi.org/10.1186/s13643-019-1037-1,PMC6528219,31109367,CC BY,"INTRODUCTION: Better characterisation of the epidemiological data on respiratory viral infections among people with acute respiratory tract infection (ARTI) can help to implement efficient strategies to curb the burden of ARTI in Africa. We will conduct a systematic review and meta-analysis to determine the prevalence and factors associated with respiratory viral infection in people of all ages with ARTI residing in Africa. METHODS: This work will include cross-sectional studies published between January 1, 2000 and December 31, 2017, without any language restriction, on populations residing in African countries. We will consider studies that reported the prevalence of respiratory viruses in people with ARTI confirmed by a polymerase chain reaction technique. We will be searching PubMed, Embase, African Journals Online, Web of Science, and Global Index Medicus. The selection of relevant studies, extraction of data, and evaluation of the quality of the articles will be carried out independently by two review authors, and the discrepancies will be resolved by consensus or intervention of a third author. The heterogeneity of the studies will be assessed using the χ(2) test on Cochrane’s Q statistic. Publication bias will be assessed by the Egger test. Studies will be pooled using a random-effect meta-analysis model. Results will be presented by age group and sub-region of Africa. Using meta-regression models, we will identify factors associated with viral infections in people with ARTI. DISCUSSION: This systematic review and meta-analysis is based on published data and therefore does not require ethical approval. This work will serve as a basis for the development of strategies for prevention and control ARTI in Africa and will also serve to identify data gaps and guide future investigations. The final report will be published in peer-reviewed journals as a scientific article and presented in workshops, conferences, and scientific conferences. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018088261. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13643-019-1037-1) contains supplementary material, which is available to authorized users.",2019 May 20,"['Kenmoe, Sebastien', 'Bigna, Jean Joel', 'Modiyinji, Abdou Fatawou', 'Simo, Fredy Brice N.', 'Njouom, Richard']",Syst Rev,,,False
8da224b5eba13cee28c3a95cb3c1e3c4d26e5a3a,PMC,Epidemiology of respiratory viral infections in people with acute respiratory tract infections in Africa: the VARIAFRICA systematic review and meta-analysis protocol,http://dx.doi.org/10.1186/s13643-019-1037-1,PMC6528219,31109367,CC BY,"INTRODUCTION: Better characterisation of the epidemiological data on respiratory viral infections among people with acute respiratory tract infection (ARTI) can help to implement efficient strategies to curb the burden of ARTI in Africa. We will conduct a systematic review and meta-analysis to determine the prevalence and factors associated with respiratory viral infection in people of all ages with ARTI residing in Africa. METHODS: This work will include cross-sectional studies published between January 1, 2000 and December 31, 2017, without any language restriction, on populations residing in African countries. We will consider studies that reported the prevalence of respiratory viruses in people with ARTI confirmed by a polymerase chain reaction technique. We will be searching PubMed, Embase, African Journals Online, Web of Science, and Global Index Medicus. The selection of relevant studies, extraction of data, and evaluation of the quality of the articles will be carried out independently by two review authors, and the discrepancies will be resolved by consensus or intervention of a third author. The heterogeneity of the studies will be assessed using the χ(2) test on Cochrane’s Q statistic. Publication bias will be assessed by the Egger test. Studies will be pooled using a random-effect meta-analysis model. Results will be presented by age group and sub-region of Africa. Using meta-regression models, we will identify factors associated with viral infections in people with ARTI. DISCUSSION: This systematic review and meta-analysis is based on published data and therefore does not require ethical approval. This work will serve as a basis for the development of strategies for prevention and control ARTI in Africa and will also serve to identify data gaps and guide future investigations. The final report will be published in peer-reviewed journals as a scientific article and presented in workshops, conferences, and scientific conferences. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018088261. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13643-019-1037-1) contains supplementary material, which is available to authorized users.",2019 May 20,"['Kenmoe, Sebastien', 'Bigna, Jean Joel', 'Modiyinji, Abdou Fatawou', 'Simo, Fredy Brice N.', 'Njouom, Richard']",Syst Rev,,,True
d9fa99532407c6f68ffa719e321870586363c18a,PMC,Weekly ILI patient ratio change prediction using news articles with support vector machine,http://dx.doi.org/10.1186/s12859-019-2894-2,PMC6528302,31109286,CC BY,"BACKGROUND: Influenza continues to pose a serious threat to human health worldwide. For this reason, detecting influenza infection patterns is critical. However, as the epidemic spread of influenza occurs sporadically and rapidly, it is not easy to estimate the future variance of influenza virus infection. Furthermore, accumulating influenza related data is not easy, because the type of data that is associated with influenza is very limited. For these reasons, identifying useful data and building a prediction model with these data are necessary steps toward predicting if the number of patients will increase or decrease. On the Internet, numerous press releases are published every day that reflect currently pending issues. RESULTS: In this research, we collected Internet articles related to infectious diseases from the Centre for Health Protection (CHP), which is maintained the by Hong Kong Department of Health, to see if news text data could be used to predict the spread of influenza. In total, 7769 articles related to infectious diseases published from 2004 January to 2018 January were collected. We evaluated the predictive ability of article text data from the period of 2013–2018 for each of the weekly time horizons. The support vector machine (SVM) model was used for prediction in order to examine the use of information embedded in the web articles and detect the pattern of influenza spread variance. The prediction result using news text data with SVM exhibited a mean accuracy of 86.7 % on predicting whether weekly ILI patient ratio would increase or decrease, and a root mean square error of 0.611 on estimating the weekly ILI patient ratio. CONCLUSIONS: In order to remedy the problems of conventional data, using news articles can be a suitable choice, because they can help estimate if ILI patient ratio will increase or decrease as well as how many patients will be affected, as shown in the result of research. Thus, advancements in research on using news articles for influenza prediction should continue to be pursed, as the result showed acceptable performance as compared to existing influenza prediction researches.",2019 May 20,"['Kim, Juhyeon', 'Ahn, Insung']",BMC Bioinformatics,,,True
322b92b3fe13a75501b634f427892409246de419,PMC,Bovine respiratory syncytial virus in experimentally exposed and rechallenged calves; viral shedding related to clinical signs and the potential for transmission,http://dx.doi.org/10.1186/s12917-019-1911-z,PMC6528318,31109324,CC BY,"BACKGROUND: Bovine respiratory syncytial virus (BRSV) is an important respiratory pathogen worldwide, detrimentally affecting the economy and animal welfare. To prevent and control BRSV infection, further knowledge on virus shedding and transmission potential in individual animals is required. This study aimed to detect viral RNA and infective virions during BRSV infection to evaluate duration of the transmission period and correlation with clinical signs of disease. The outcome of BRSV re-exposure on calves, their housing environment and effect of introduction of sentinel calves was also investigated. A live animal experiment including 10 calves was conducted over 61 days. Initially, two calves were inoculated with a non-passaged BRSV field isolate. Two days later, six naïve calves (EG: Exposed group) were introduced for commingling and four weeks later, another two naïve calves (SG: Sentinel group) were introduced. Seven weeks after commingling, EG animals were re-inoculated. Clinical examination was performed daily. Nasal swabs were collected regularly and analysed for viral RNA by RT-ddPCR, while virus isolation was performed in cell culture. BRSV serology was performed with ELISA. RESULTS: All the EG calves seroconverted and showed clinical signs of respiratory disease. Viral RNA was detected from days 1–27 after exposure, while the infective virus was isolated on day 6 and 13. On day 19, all animals were seropositive and virus could not be isolated. Total clinical score for respiratory signs corresponded well with the shedding of viral RNA. The SG animals, introduced 27 days after exposure, remained negative for BRSV RNA and stayed seronegative throughout the study. Inoculation of the EG calves seven weeks after primary infection did not lead to new shedding of viral RNA or clinical signs of disease. CONCLUSION: Viral RNA was detected in nasal swabs from the calves up to four weeks after exposure. The detection and amount of viral RNA corresponded well with the degree of respiratory signs. The calves were shedding infective virions for a considerable shorter period, and naïve calves introduced after four weeks were not infected. Infected calves were protected from reinfection for at least seven weeks. This knowledge is useful to prevent spread of BRSV.",2019 May 20,"['Klem, Thea Blystad', 'Sjurseth, Siri Kulberg', 'Sviland, Ståle', 'Gjerset, Britt', 'Myrmel, Mette', 'Stokstad, Maria']",BMC Vet Res,,,True
5e69bc12b5603039722d86b5b9b770dcb5470a98,PMC,Which Threats to Global Health Pose a Problem for Turkey’s Health?,http://dx.doi.org/10.4274/balkanmedj.galenos.2019.2019.3.001,PMC6528528,30821137,CC BY,,2019 May 10,"Tokuç, Burcu",Balkan Med J,,,True
37cae647fffbd8ed2ba338d805a6029577621c1d,PMC,Perturbation of Thymocyte Development Underlies the PRRS Pandemic: A Testable Hypothesis,http://dx.doi.org/10.3389/fimmu.2019.01077,PMC6529568,31156633,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) causes immune dysregulation during the Critical Window of Immunological Development. We hypothesize that thymocyte development is altered by infected thymic antigen presenting cells (TAPCs) in the fetal/neonatal thymus that interact with double-positive thymocytes causing an acute deficiency of T cells that produces “holes” in the T cell repertoire allowing for poor recognition of PRRSV and other neonatal pathogens. The deficiency may be the result of random elimination of PRRSV-specific T cells or the generation of T cells that accept PRRSV epitopes as self-antigens. Loss of helper T cells for virus neutralizing (VN) epitopes can result in the failure of selection for B cells in lymph node germinal centers capable of producing high affinity VN antibodies. Generation of cytotoxic and regulatory T cells may also be impaired. Similar to infections with LDV, LCMV, MCMV, HIV-1 and trypanosomes, the host responds to the deficiency of pathogen-specific T cells and perhaps regulatory T cells, by “last ditch” polyclonal B cell activation. In colostrum-deprived PRRSV-infected isolator piglets, this results in hypergammaglobulinemia, which we believe to be a “red herring” that detracts attention from the thymic atrophy story, but leads to our second independent hypothesis. Since hypergammaglobulinemia has not been reported in PRRSV-infected conventionally-reared piglets, we hypothesize that this is due to the down-regulatory effect of passive maternal IgG and cytokines in porcine colostrum, especially TGFβ which stimulates development of regulatory T cells (Tregs).",2019 May 15,"['Butler, John E.', 'Sinkora, Marek', 'Wang, Gang', 'Stepanova, Katerina', 'Li, Yuming', 'Cai, Xuehui']",Front Immunol,,,True
2686a3eb4a97b4cd2f1d9b05018dbe2b28df410d,PMC,Cyberbiosecurity Challenges of Pathogen Genome Databases,http://dx.doi.org/10.3389/fbioe.2019.00106,PMC6529814,31157218,CC BY,"Pathogen detection, identification, and tracking is shifting from non-molecular methods, DNA fingerprinting methods, and single gene methods to methods relying on whole genomes. Viral Ebola and influenza genome data are being used for real-time tracking, while food-borne bacterial pathogen outbreaks and hospital outbreaks are investigated using whole genomes in the UK, Canada, the USA and the other countries. Also, plant pathogen genomes are starting to be used to investigate plant disease epidemics such as the wheat blast outbreak in Bangladesh. While these genome-based approaches provide never-seen advantages over all previous approaches with regard to public health and biosecurity, they also come with new vulnerabilities and risks with regard to cybersecurity. The more we rely on genome databases, the more likely these databases will become targets for cyber-attacks to interfere with public health and biosecurity systems by compromising their integrity, taking them hostage, or manipulating the data they contain. Also, while there is the potential to collect pathogen genomic data from infected individuals or agricultural and food products during disease outbreaks to improve disease modeling and forecast, how to protect the privacy of individuals, growers, and retailers is another major cyberbiosecurity challenge. As data become linkable to other data sources, individuals and groups become identifiable and potential malicious activities targeting those identified become feasible. Here, we define a number of potential cybersecurity weaknesses in today's pathogen genome databases to raise awareness, and we provide potential solutions to strengthen cyberbiosecurity during the development of the next generation of pathogen genome databases.",2019 May 15,"['Vinatzer, Boris A.', 'Heath, Lenwood S.', 'Almohri, Hussain M. J.', 'Stulberg, Michael J.', 'Lowe, Christopher', 'Li, Song']",Front Bioeng Biotechnol,,,True
15bb982468f51e3afa956146106c9affc99f43d8,PMC,IRF1 Maintains Optimal Constitutive Expression of Antiviral Genes and Regulates the Early Antiviral Response,http://dx.doi.org/10.3389/fimmu.2019.01019,PMC6529937,31156620,CC BY,"Viral defense at mucosal sites depends on interferons (IFN) and IFN stimulated genes (ISGs), either of which may be constitutively expressed to maintain an “antiviral state” (AVS). However, the mechanisms that govern the AVS are poorly defined. Using a BEAS-2B respiratory epithelial cell line deficient in IRF1, we demonstrate higher susceptibility to infection with vesicular stomatitis virus (VSV) and influenza virus. IRF1-mediated restriction of VSV is IFN-independent, as blockade of types I and III IFNs and JAK-STAT signaling before infection did not affect VSV infection of either parent or IRF1 KO cells. Transcriptome analysis revealed that IRF1 regulates constitutive expression of ~300 genes, including antiviral ISGs: OAS2, BST2, and RNASEL and knockdown of any of these IRF1-dependent genes increased VSV infection. Additionally, IRF1 enhances rapid expression of IFNβ and IFNλ after stimulation with poly I:C and also regulates ISG expression. Mechanistically, IRF1 enhances recruitment of BRD4 to promotor-enhancer regions of ISGs for rapid expression and maintains levels of histone H3K4me1 for optimal constitutive expression. Finally, IRF1 also regulates constitutive expression of TLR2 and TLR3 and promotes signaling through these pattern recognition receptors (PRR). These data reveal multiple roles for IRF1 toward effective anti-viral responses by maintaining IFN-independent constitutive expression of anti-viral ISGs and supporting early IFN-dependent responses to PRR stimulation.",2019 May 15,"['Panda, Debasis', 'Gjinaj, Erisa', 'Bachu, Mahesh', 'Squire, Erica', 'Novatt, Hilary', 'Ozato, Keiko', 'Rabin, Ronald L.']",Front Immunol,,,False
c3c25b9a548eebd5505b4f20d75fa99a08ab88dd,PMC,IRF1 Maintains Optimal Constitutive Expression of Antiviral Genes and Regulates the Early Antiviral Response,http://dx.doi.org/10.3389/fimmu.2019.01019,PMC6529937,31156620,CC BY,"Viral defense at mucosal sites depends on interferons (IFN) and IFN stimulated genes (ISGs), either of which may be constitutively expressed to maintain an “antiviral state” (AVS). However, the mechanisms that govern the AVS are poorly defined. Using a BEAS-2B respiratory epithelial cell line deficient in IRF1, we demonstrate higher susceptibility to infection with vesicular stomatitis virus (VSV) and influenza virus. IRF1-mediated restriction of VSV is IFN-independent, as blockade of types I and III IFNs and JAK-STAT signaling before infection did not affect VSV infection of either parent or IRF1 KO cells. Transcriptome analysis revealed that IRF1 regulates constitutive expression of ~300 genes, including antiviral ISGs: OAS2, BST2, and RNASEL and knockdown of any of these IRF1-dependent genes increased VSV infection. Additionally, IRF1 enhances rapid expression of IFNβ and IFNλ after stimulation with poly I:C and also regulates ISG expression. Mechanistically, IRF1 enhances recruitment of BRD4 to promotor-enhancer regions of ISGs for rapid expression and maintains levels of histone H3K4me1 for optimal constitutive expression. Finally, IRF1 also regulates constitutive expression of TLR2 and TLR3 and promotes signaling through these pattern recognition receptors (PRR). These data reveal multiple roles for IRF1 toward effective anti-viral responses by maintaining IFN-independent constitutive expression of anti-viral ISGs and supporting early IFN-dependent responses to PRR stimulation.",2019 May 15,"['Panda, Debasis', 'Gjinaj, Erisa', 'Bachu, Mahesh', 'Squire, Erica', 'Novatt, Hilary', 'Ozato, Keiko', 'Rabin, Ronald L.']",Front Immunol,,,True
6bf5a9bc71d23a14273e34f2a3dc8f3de54268b9,PMC,A Statistical Similarity/Dissimilarity Analysis of Protein Sequences Based on a Novel Group Representative Vector,http://dx.doi.org/10.1155/2019/8702968,PMC6530227,31205946,CC BY,"Similarity/dissimilarity analysis is a key way of understanding the biology of an organism by knowing the origin of the new genes/sequences. Sequence data are grouped in terms of biological relationships. The number of sequences related to any group is susceptible to be increased every day. All the present alignment-free methods approve the utility of their approaches by producing a similarity/dissimilarity matrix. Although this matrix is clear, it measures the degree of similarity among sequences individually. In our work, a representative of each of three groups of protein sequences is introduced. A similarity/dissimilarity vector is evaluated instead of the ordinary similarity/dissimilarity matrix based on the group representative. The approach is applied on three selected groups of protein sequences: beta globin, NADH dehydrogenase subunit 5 (ND5), and spike protein sequences. A cross-grouping comparison is produced to ensure the singularity of each group. A qualitative comparison between our approach, previous articles, and the phylogenetic tree of these protein sequences proved the utility of our approach.",2019 May 8,"['Abd Elwahaab, Marwa A.', 'Abo-Elkhier, Mervat M.', 'Abo el Maaty, Moheb I.']",Biomed Res Int,,,False
46e0a035e55b44ef196234e32b2c550b87db4fdc,PMC,A Statistical Similarity/Dissimilarity Analysis of Protein Sequences Based on a Novel Group Representative Vector,http://dx.doi.org/10.1155/2019/8702968,PMC6530227,31205946,CC BY,"Similarity/dissimilarity analysis is a key way of understanding the biology of an organism by knowing the origin of the new genes/sequences. Sequence data are grouped in terms of biological relationships. The number of sequences related to any group is susceptible to be increased every day. All the present alignment-free methods approve the utility of their approaches by producing a similarity/dissimilarity matrix. Although this matrix is clear, it measures the degree of similarity among sequences individually. In our work, a representative of each of three groups of protein sequences is introduced. A similarity/dissimilarity vector is evaluated instead of the ordinary similarity/dissimilarity matrix based on the group representative. The approach is applied on three selected groups of protein sequences: beta globin, NADH dehydrogenase subunit 5 (ND5), and spike protein sequences. A cross-grouping comparison is produced to ensure the singularity of each group. A qualitative comparison between our approach, previous articles, and the phylogenetic tree of these protein sequences proved the utility of our approach.",2019 May 8,"['Abd Elwahaab, Marwa A.', 'Abo-Elkhier, Mervat M.', 'Abo el Maaty, Moheb I.']",Biomed Res Int,,,True
cc563b84c16c4fe4fb1fbd3baa6ffd08dda70006,PMC,Rapid and Sensitive Recombinase Polymerase Amplification Combined With Lateral Flow Strip for Detecting African Swine Fever Virus,http://dx.doi.org/10.3389/fmicb.2019.01004,PMC6530510,31156571,CC BY,"African swine fever virus (ASFV), the etiological agent of African swine fever (ASF), a hemorrhagic fever of domestic pigs, has devastating consequences for the pig farming industry. More than 1,000,000 pigs have been slaughtered since 3 August 2018 in China. However, vaccines or drugs for ASF have yet to be developed. As such, a rapid test that can accurately detect ASFV on-site is important to the timely implementation of control measures. In this study, we developed a rapid test that combines recombinase polymerase amplification (RPA) of the ASFV p72 gene with lateral flow detection (LFD). Results showed that the sensitivity of recombinase polymerase amplification with lateral flow dipstick (RPA-LFD) for ASFV was 150 copies per reaction within 10 min at 38°C. The assay was highly specific to ASFV and had no cross-reactions with other porcine viruses, including classical swine fever virus (CSFV). A total of 145 field samples were examined using our method, and the agreement of the positive rate between RPA-LFD (10/145) and real-time PCR (10/145) was 100%. Overall, RPA-LFD provides a novel alternative for the simple, sensitive, and specific identification of ASFV and showed potential for on-site ASFV detection.",2019 May 15,"['Miao, Faming', 'Zhang, Jingyuan', 'Li, Nan', 'Chen, Teng', 'Wang, Lidong', 'Zhang, Fei', 'Mi, Lijuan', 'Zhang, Jinxia', 'Wang, Shuchao', 'Wang, Ying', 'Zhou, Xintao', 'Zhang, Yanyan', 'Li, Min', 'Zhang, Shoufeng', 'Hu, Rongliang']",Front Microbiol,,,True
2748111c3683cdd338b098c0b5d2aa6becfc0fee,PMC,Identification of a Novel Hypovirulence-Inducing Hypovirus From Alternaria alternata,http://dx.doi.org/10.3389/fmicb.2019.01076,PMC6530530,31156589,CC BY,"Mycoviruses are wide spread throughout almost all groups of fungi but only a small number of mycoviruses can attenuate the growth and virulence of their fungal hosts. Alternaria alternata is an ascomycete fungus that causes leaf spot diseases on various crop plants. In this study, we identified a novel ssRNA mycovirus infecting an A. alternata f. sp. mali strain isolated from an apple orchard in China. Sequence analyses revealed that this virus is related to hypoviruses, in particular to Wuhan insect virus 14, an unclassified hypovirus identified from insect meta-transcriptomics, as well as other hypoviruses belonging to the genus Hypovirus, and therefore this virus is designed as Alternaria alternata hypovirus 1 (AaHV1). The genome of AaHV1 contains a single large open-reading frame encoding a putative polyprotein (∼479 kDa) with a cysteine proteinase-like and replication-associated domains. Curing AaHV1 from the fungal host strain indicated that the virus is responsible for the slow growth and reduced virulence of the host. AaHV1 defective RNA (D-RNA) with internal deletions emerging during fungal subcultures but the presence of D-RNA does not affect AaHV1 accumulation and pathogenicities. Moreover, AaHV1 could replicate and confer hypovirulence in Botryosphaeria dothidea, a fungal pathogen of apple white rot disease. This finding could facilitate better understanding of A. alternata pathogenicity and is relevant for development of biocontrol methods of fungal diseases.",2019 May 15,"['Li, Huan', 'Bian, Ruiling', 'Liu, Qian', 'Yang, Liu', 'Pang, Tianxing', 'Salaipeth, Lakha', 'Andika, Ida Bagus', 'Kondo, Hideki', 'Sun, Liying']",Front Microbiol,,,True
37212033355072dde6cd613e4431c5ce3e864ba4,PMC,Identification of a Novel Hypovirulence-Inducing Hypovirus From Alternaria alternata,http://dx.doi.org/10.3389/fmicb.2019.01076,PMC6530530,31156589,CC BY,"Mycoviruses are wide spread throughout almost all groups of fungi but only a small number of mycoviruses can attenuate the growth and virulence of their fungal hosts. Alternaria alternata is an ascomycete fungus that causes leaf spot diseases on various crop plants. In this study, we identified a novel ssRNA mycovirus infecting an A. alternata f. sp. mali strain isolated from an apple orchard in China. Sequence analyses revealed that this virus is related to hypoviruses, in particular to Wuhan insect virus 14, an unclassified hypovirus identified from insect meta-transcriptomics, as well as other hypoviruses belonging to the genus Hypovirus, and therefore this virus is designed as Alternaria alternata hypovirus 1 (AaHV1). The genome of AaHV1 contains a single large open-reading frame encoding a putative polyprotein (∼479 kDa) with a cysteine proteinase-like and replication-associated domains. Curing AaHV1 from the fungal host strain indicated that the virus is responsible for the slow growth and reduced virulence of the host. AaHV1 defective RNA (D-RNA) with internal deletions emerging during fungal subcultures but the presence of D-RNA does not affect AaHV1 accumulation and pathogenicities. Moreover, AaHV1 could replicate and confer hypovirulence in Botryosphaeria dothidea, a fungal pathogen of apple white rot disease. This finding could facilitate better understanding of A. alternata pathogenicity and is relevant for development of biocontrol methods of fungal diseases.",2019 May 15,"['Li, Huan', 'Bian, Ruiling', 'Liu, Qian', 'Yang, Liu', 'Pang, Tianxing', 'Salaipeth, Lakha', 'Andika, Ida Bagus', 'Kondo, Hideki', 'Sun, Liying']",Front Microbiol,,,False
d150551dd14158a4aee11fb6c2913a0d58c91163,PMC,Relevance of Autophagy Induction by Gastrointestinal Hormones: Focus on the Incretin-Based Drug Target and Glucagon,http://dx.doi.org/10.3389/fphar.2019.00476,PMC6531852,31156426,CC BY,"The biology of autophagy in health and disease conditions has been intensively analyzed for decades. Several potential interventions can induce autophagy in preclinical research; however, none of these interventions are ready for translation to clinical practice yet. The topic of the current review is the molecular regulation of autophagy by glucagon, glucagon-like peptide (GLP)-1 and the GLP-1-degrading enzyme dipeptidyl peptidase-4 (DPP-4). Glucagon is a well-known polypeptide that induces autophagy. In contrast, GLP-1 has been shown to inhibit glucagon secretion; GLP-1 also has been related to the induction of autophagy. DPP-4 inhibitors can induce autophagy in a GLP-1–dependent manner, but other diverse effects could be relevant. Here, we analyze the distinct molecular regulation of autophagy by glucagon, GLP-1, and DPP-4 inhibitors. Additionally, the potential contribution to autophagy by glucagon and GLP-1 after bariatric surgery is discussed.",2019 May 16,"['Kanasaki, Keizo', 'Kawakita, Emi', 'Koya, Daisuke']",Front Pharmacol,,,True
cb04b7111c59c623bd68cf0441f18ccfcddb5b40,PMC,Kinome-Wide RNA Interference Screening Identifies Mitogen-Activated Protein Kinases and Phosphatidylinositol Metabolism as Key Factors for Rabies Virus Infection,http://dx.doi.org/10.1128/mSphere.00047-19,PMC6531879,31118297,CC BY,"Throughout the rabies virus (RABV) infectious cycle, host-virus interactions define its capacity to replicate, escape the immune response, and spread. As phosphorylation is a key regulatory mechanism involved in most cellular processes, kinases represent a target of choice to identify host factors required for viral replication. A kinase and phosphatase small interfering RNA (siRNA) high-content screening was performed on a fluorescent protein-recombinant field isolate (Tha RABV). We identified 57 high-confidence key host factors important for RABV replication with a readout set at 18 h postinfection and 73 with a readout set at 36 h postinfection, including 24 common factors at all stages of the infection. Amongst them, gene clusters of the most prominent pathways were determined. Up to 15 mitogen-activated protein kinases (MAPKs) and effectors, including MKK7 (associated with Jun N-terminal protein kinase [JNK] signalization) and DUSP5, as well as 17 phosphatidylinositol (PI)-related proteins, including PIP5K1C and MTM1, were found to be involved in the later stage of RABV infection. The importance of these pathways was further validated, as small molecules Ro 31-8820 and PD 198306 inhibited RABV replication in human neurons. IMPORTANCE Rabies virus relies on cellular machinery for its replication while simultaneously evading the host immune response. Despite their importance, little is known about the key host factors required for rabies virus infection. Here, we focused on the human kinome, at the core of many cellular pathways, to unveil a new understanding of the rabies virus infectious cycle and to discover new potential therapeutic targets in a small interfering RNA screening. The mitogen-activated protein kinase pathway and phosphatidylinositol metabolism were identified as prominent factors involved in rabies virus infection, and those findings were further confirmed in human neurons. While bringing a new insight into rabies virus biology, we also provide a new list of host factors involved in rabies virus infection.",2019 May 22,"['Besson, Benoit', 'Kim, Seonhee', 'Kim, Taehee', 'Ko, Yoonae', 'Lee, Sangchul', 'Larrous, Florence', 'Song, Jihwan', 'Shum, David', 'Grailhe, Regis', 'Bourhy, Hervé']",mSphere,,,True
79a0f19a4e1f786f96d4882f85a185630004aab0,PMC,Kinome-Wide RNA Interference Screening Identifies Mitogen-Activated Protein Kinases and Phosphatidylinositol Metabolism as Key Factors for Rabies Virus Infection,http://dx.doi.org/10.1128/mSphere.00047-19,PMC6531879,31118297,CC BY,"Throughout the rabies virus (RABV) infectious cycle, host-virus interactions define its capacity to replicate, escape the immune response, and spread. As phosphorylation is a key regulatory mechanism involved in most cellular processes, kinases represent a target of choice to identify host factors required for viral replication. A kinase and phosphatase small interfering RNA (siRNA) high-content screening was performed on a fluorescent protein-recombinant field isolate (Tha RABV). We identified 57 high-confidence key host factors important for RABV replication with a readout set at 18 h postinfection and 73 with a readout set at 36 h postinfection, including 24 common factors at all stages of the infection. Amongst them, gene clusters of the most prominent pathways were determined. Up to 15 mitogen-activated protein kinases (MAPKs) and effectors, including MKK7 (associated with Jun N-terminal protein kinase [JNK] signalization) and DUSP5, as well as 17 phosphatidylinositol (PI)-related proteins, including PIP5K1C and MTM1, were found to be involved in the later stage of RABV infection. The importance of these pathways was further validated, as small molecules Ro 31-8820 and PD 198306 inhibited RABV replication in human neurons. IMPORTANCE Rabies virus relies on cellular machinery for its replication while simultaneously evading the host immune response. Despite their importance, little is known about the key host factors required for rabies virus infection. Here, we focused on the human kinome, at the core of many cellular pathways, to unveil a new understanding of the rabies virus infectious cycle and to discover new potential therapeutic targets in a small interfering RNA screening. The mitogen-activated protein kinase pathway and phosphatidylinositol metabolism were identified as prominent factors involved in rabies virus infection, and those findings were further confirmed in human neurons. While bringing a new insight into rabies virus biology, we also provide a new list of host factors involved in rabies virus infection.",2019 May 22,"['Besson, Benoit', 'Kim, Seonhee', 'Kim, Taehee', 'Ko, Yoonae', 'Lee, Sangchul', 'Larrous, Florence', 'Song, Jihwan', 'Shum, David', 'Grailhe, Regis', 'Bourhy, Hervé']",mSphere,,,False
d993ca98550994dcf40ce6d087e7af158283b31e,PMC,Kinome-Wide RNA Interference Screening Identifies Mitogen-Activated Protein Kinases and Phosphatidylinositol Metabolism as Key Factors for Rabies Virus Infection,http://dx.doi.org/10.1128/mSphere.00047-19,PMC6531879,31118297,CC BY,"Throughout the rabies virus (RABV) infectious cycle, host-virus interactions define its capacity to replicate, escape the immune response, and spread. As phosphorylation is a key regulatory mechanism involved in most cellular processes, kinases represent a target of choice to identify host factors required for viral replication. A kinase and phosphatase small interfering RNA (siRNA) high-content screening was performed on a fluorescent protein-recombinant field isolate (Tha RABV). We identified 57 high-confidence key host factors important for RABV replication with a readout set at 18 h postinfection and 73 with a readout set at 36 h postinfection, including 24 common factors at all stages of the infection. Amongst them, gene clusters of the most prominent pathways were determined. Up to 15 mitogen-activated protein kinases (MAPKs) and effectors, including MKK7 (associated with Jun N-terminal protein kinase [JNK] signalization) and DUSP5, as well as 17 phosphatidylinositol (PI)-related proteins, including PIP5K1C and MTM1, were found to be involved in the later stage of RABV infection. The importance of these pathways was further validated, as small molecules Ro 31-8820 and PD 198306 inhibited RABV replication in human neurons. IMPORTANCE Rabies virus relies on cellular machinery for its replication while simultaneously evading the host immune response. Despite their importance, little is known about the key host factors required for rabies virus infection. Here, we focused on the human kinome, at the core of many cellular pathways, to unveil a new understanding of the rabies virus infectious cycle and to discover new potential therapeutic targets in a small interfering RNA screening. The mitogen-activated protein kinase pathway and phosphatidylinositol metabolism were identified as prominent factors involved in rabies virus infection, and those findings were further confirmed in human neurons. While bringing a new insight into rabies virus biology, we also provide a new list of host factors involved in rabies virus infection.",2019 May 22,"['Besson, Benoit', 'Kim, Seonhee', 'Kim, Taehee', 'Ko, Yoonae', 'Lee, Sangchul', 'Larrous, Florence', 'Song, Jihwan', 'Shum, David', 'Grailhe, Regis', 'Bourhy, Hervé']",mSphere,,,False
29a1b47db8b938b797ec8a86c014ed47050e1647,PMC,Kinome-Wide RNA Interference Screening Identifies Mitogen-Activated Protein Kinases and Phosphatidylinositol Metabolism as Key Factors for Rabies Virus Infection,http://dx.doi.org/10.1128/mSphere.00047-19,PMC6531879,31118297,CC BY,"Throughout the rabies virus (RABV) infectious cycle, host-virus interactions define its capacity to replicate, escape the immune response, and spread. As phosphorylation is a key regulatory mechanism involved in most cellular processes, kinases represent a target of choice to identify host factors required for viral replication. A kinase and phosphatase small interfering RNA (siRNA) high-content screening was performed on a fluorescent protein-recombinant field isolate (Tha RABV). We identified 57 high-confidence key host factors important for RABV replication with a readout set at 18 h postinfection and 73 with a readout set at 36 h postinfection, including 24 common factors at all stages of the infection. Amongst them, gene clusters of the most prominent pathways were determined. Up to 15 mitogen-activated protein kinases (MAPKs) and effectors, including MKK7 (associated with Jun N-terminal protein kinase [JNK] signalization) and DUSP5, as well as 17 phosphatidylinositol (PI)-related proteins, including PIP5K1C and MTM1, were found to be involved in the later stage of RABV infection. The importance of these pathways was further validated, as small molecules Ro 31-8820 and PD 198306 inhibited RABV replication in human neurons. IMPORTANCE Rabies virus relies on cellular machinery for its replication while simultaneously evading the host immune response. Despite their importance, little is known about the key host factors required for rabies virus infection. Here, we focused on the human kinome, at the core of many cellular pathways, to unveil a new understanding of the rabies virus infectious cycle and to discover new potential therapeutic targets in a small interfering RNA screening. The mitogen-activated protein kinase pathway and phosphatidylinositol metabolism were identified as prominent factors involved in rabies virus infection, and those findings were further confirmed in human neurons. While bringing a new insight into rabies virus biology, we also provide a new list of host factors involved in rabies virus infection.",2019 May 22,"['Besson, Benoit', 'Kim, Seonhee', 'Kim, Taehee', 'Ko, Yoonae', 'Lee, Sangchul', 'Larrous, Florence', 'Song, Jihwan', 'Shum, David', 'Grailhe, Regis', 'Bourhy, Hervé']",mSphere,,,False
eb869313e793af520e10df92b34b3e0e6a277d9d,PMC,Kinome-Wide RNA Interference Screening Identifies Mitogen-Activated Protein Kinases and Phosphatidylinositol Metabolism as Key Factors for Rabies Virus Infection,http://dx.doi.org/10.1128/mSphere.00047-19,PMC6531879,31118297,CC BY,"Throughout the rabies virus (RABV) infectious cycle, host-virus interactions define its capacity to replicate, escape the immune response, and spread. As phosphorylation is a key regulatory mechanism involved in most cellular processes, kinases represent a target of choice to identify host factors required for viral replication. A kinase and phosphatase small interfering RNA (siRNA) high-content screening was performed on a fluorescent protein-recombinant field isolate (Tha RABV). We identified 57 high-confidence key host factors important for RABV replication with a readout set at 18 h postinfection and 73 with a readout set at 36 h postinfection, including 24 common factors at all stages of the infection. Amongst them, gene clusters of the most prominent pathways were determined. Up to 15 mitogen-activated protein kinases (MAPKs) and effectors, including MKK7 (associated with Jun N-terminal protein kinase [JNK] signalization) and DUSP5, as well as 17 phosphatidylinositol (PI)-related proteins, including PIP5K1C and MTM1, were found to be involved in the later stage of RABV infection. The importance of these pathways was further validated, as small molecules Ro 31-8820 and PD 198306 inhibited RABV replication in human neurons. IMPORTANCE Rabies virus relies on cellular machinery for its replication while simultaneously evading the host immune response. Despite their importance, little is known about the key host factors required for rabies virus infection. Here, we focused on the human kinome, at the core of many cellular pathways, to unveil a new understanding of the rabies virus infectious cycle and to discover new potential therapeutic targets in a small interfering RNA screening. The mitogen-activated protein kinase pathway and phosphatidylinositol metabolism were identified as prominent factors involved in rabies virus infection, and those findings were further confirmed in human neurons. While bringing a new insight into rabies virus biology, we also provide a new list of host factors involved in rabies virus infection.",2019 May 22,"['Besson, Benoit', 'Kim, Seonhee', 'Kim, Taehee', 'Ko, Yoonae', 'Lee, Sangchul', 'Larrous, Florence', 'Song, Jihwan', 'Shum, David', 'Grailhe, Regis', 'Bourhy, Hervé']",mSphere,,,False
3170fe9153e84107073f2f349d6d8f5a179fc4a1,PMC,Kinome-Wide RNA Interference Screening Identifies Mitogen-Activated Protein Kinases and Phosphatidylinositol Metabolism as Key Factors for Rabies Virus Infection,http://dx.doi.org/10.1128/mSphere.00047-19,PMC6531879,31118297,CC BY,"Throughout the rabies virus (RABV) infectious cycle, host-virus interactions define its capacity to replicate, escape the immune response, and spread. As phosphorylation is a key regulatory mechanism involved in most cellular processes, kinases represent a target of choice to identify host factors required for viral replication. A kinase and phosphatase small interfering RNA (siRNA) high-content screening was performed on a fluorescent protein-recombinant field isolate (Tha RABV). We identified 57 high-confidence key host factors important for RABV replication with a readout set at 18 h postinfection and 73 with a readout set at 36 h postinfection, including 24 common factors at all stages of the infection. Amongst them, gene clusters of the most prominent pathways were determined. Up to 15 mitogen-activated protein kinases (MAPKs) and effectors, including MKK7 (associated with Jun N-terminal protein kinase [JNK] signalization) and DUSP5, as well as 17 phosphatidylinositol (PI)-related proteins, including PIP5K1C and MTM1, were found to be involved in the later stage of RABV infection. The importance of these pathways was further validated, as small molecules Ro 31-8820 and PD 198306 inhibited RABV replication in human neurons. IMPORTANCE Rabies virus relies on cellular machinery for its replication while simultaneously evading the host immune response. Despite their importance, little is known about the key host factors required for rabies virus infection. Here, we focused on the human kinome, at the core of many cellular pathways, to unveil a new understanding of the rabies virus infectious cycle and to discover new potential therapeutic targets in a small interfering RNA screening. The mitogen-activated protein kinase pathway and phosphatidylinositol metabolism were identified as prominent factors involved in rabies virus infection, and those findings were further confirmed in human neurons. While bringing a new insight into rabies virus biology, we also provide a new list of host factors involved in rabies virus infection.",2019 May 22,"['Besson, Benoit', 'Kim, Seonhee', 'Kim, Taehee', 'Ko, Yoonae', 'Lee, Sangchul', 'Larrous, Florence', 'Song, Jihwan', 'Shum, David', 'Grailhe, Regis', 'Bourhy, Hervé']",mSphere,,,False
bcf9b456057b1ae5bc4f694a738f3fb2bc41e57e,PMC,Kinome-Wide RNA Interference Screening Identifies Mitogen-Activated Protein Kinases and Phosphatidylinositol Metabolism as Key Factors for Rabies Virus Infection,http://dx.doi.org/10.1128/mSphere.00047-19,PMC6531879,31118297,CC BY,"Throughout the rabies virus (RABV) infectious cycle, host-virus interactions define its capacity to replicate, escape the immune response, and spread. As phosphorylation is a key regulatory mechanism involved in most cellular processes, kinases represent a target of choice to identify host factors required for viral replication. A kinase and phosphatase small interfering RNA (siRNA) high-content screening was performed on a fluorescent protein-recombinant field isolate (Tha RABV). We identified 57 high-confidence key host factors important for RABV replication with a readout set at 18 h postinfection and 73 with a readout set at 36 h postinfection, including 24 common factors at all stages of the infection. Amongst them, gene clusters of the most prominent pathways were determined. Up to 15 mitogen-activated protein kinases (MAPKs) and effectors, including MKK7 (associated with Jun N-terminal protein kinase [JNK] signalization) and DUSP5, as well as 17 phosphatidylinositol (PI)-related proteins, including PIP5K1C and MTM1, were found to be involved in the later stage of RABV infection. The importance of these pathways was further validated, as small molecules Ro 31-8820 and PD 198306 inhibited RABV replication in human neurons. IMPORTANCE Rabies virus relies on cellular machinery for its replication while simultaneously evading the host immune response. Despite their importance, little is known about the key host factors required for rabies virus infection. Here, we focused on the human kinome, at the core of many cellular pathways, to unveil a new understanding of the rabies virus infectious cycle and to discover new potential therapeutic targets in a small interfering RNA screening. The mitogen-activated protein kinase pathway and phosphatidylinositol metabolism were identified as prominent factors involved in rabies virus infection, and those findings were further confirmed in human neurons. While bringing a new insight into rabies virus biology, we also provide a new list of host factors involved in rabies virus infection.",2019 May 22,"['Besson, Benoit', 'Kim, Seonhee', 'Kim, Taehee', 'Ko, Yoonae', 'Lee, Sangchul', 'Larrous, Florence', 'Song, Jihwan', 'Shum, David', 'Grailhe, Regis', 'Bourhy, Hervé']",mSphere,,,False
3ef4a3e163427c45ff6d34808df3656167f6b855,PMC,Dietary Quercetin Increases Colonic Microbial Diversity and Attenuates Colitis Severity in Citrobacter rodentium-Infected Mice,http://dx.doi.org/10.3389/fmicb.2019.01092,PMC6531918,31156598,CC BY,"Disturbed balance between microbiota, epithelial cells, and resident immune cells within the intestine contributes to inflammatory bowel disease (IBD) pathogenesis. The Citrobacter rodentium-induced colitis mouse model has been well documented. This model allows the analysis of host responses to enteric bacteria and facilitates improved understanding of the potential mechanisms of IBD pathogenesis. The current study evaluated the effects of dietary 30 mg/kg quercetin supplementation on C. rodentium-induced experimental colitis in C57BL/6 mice. Following dietary quercetin supplementation, the mice were infected with 5 × 10(8) CFU C. rodentium, and the pathological effects of C. rodentium were measured. The results showed that quercetin alleviated the effects of C. rodentium-induced colitis, suppressed the production of pro-inflammatory cytokines, such as interleukin (IL)-17, tumor necrosis factor alpha, and IL-6 (p < 0.05), and promoted the production of IL-10 in the colon tissues (p < 0.05). Quercetin supplementation also enhanced the populations of Bacteroides, Bifidobacterium, Lactobacillus, and Clostridia and significantly reduced those of Fusobacterium and Enterococcus (p < 0.05). These findings indicate that dietary quercetin exerts therapeutic effects on C. rodentium-induced colitis, probably due to quercetin’s ability to suppress pro-inflammatory cytokines and/or modify gut microbiota. Thus, these results suggest that quercetin supplementation is effective in controlling C. rodentium-induced inflammation.",2019 May 16,"['Lin, Rui', 'Piao, Meiyu', 'Song, Yan']",Front Microbiol,,,True
b2d7e294cc9cffc5de442aef23ef615f70e3c746,PMC,Functional Involvement of Interferon-Inducible Transmembrane Proteins in Antiviral Immunity,http://dx.doi.org/10.3389/fmicb.2019.01097,PMC6532022,31156602,CC BY,"Interferons (IFNs) play crucial roles in host defense against viral infections by inducing the expression of numerous IFN-stimulated genes (ISGs) that can activate host antiviral immunity. Interferon-inducible transmembrane proteins (IFITMs), a family of small transmembrane proteins, are critical ISG products. Compelling evidence has implicated that IFITMs can establish an innate immune state to eliminate pathogens efficiently. IFITM proteins can impede broad-spectrum viral infection through various mechanisms. It is generally believed that IFITMs can block the viral entry by suppressing viral membrane fusion. However, some findings indicated that IFITMs might also inhibit viral gene expression and viral protein synthesis and thereby impair viral replication. IFITMs may incorporate into virions during viral assembly and thus reduce the infectivity of nascent virions. The precise inhibitory mechanism of IFITMs on viral infection and replication still requires further exploration. In this review, we highlight the recent findings regarding critical roles of IFITMs in host-virus interaction. We also discuss the molecular mechanisms underlying their functions in antiviral responses.",2019 May 16,"['Liao, Yuan', 'Goraya, Mohsan Ullah', 'Yuan, Xu', 'Zhang, Baoge', 'Chiu, Shih-Hsin', 'Chen, Ji-Long']",Front Microbiol,,,True
3df56c2e76799309cc7bdbc5ef8f968a1569a08c,PMC,Fecal Viral Diversity of Captive and Wild Tasmanian Devils Characterized Using Virion-Enriched Metagenomics and Metatranscriptomics,http://dx.doi.org/10.1128/JVI.00205-19,PMC6532096,30867308,CC BY,"The Tasmanian devil is an endangered carnivorous marsupial threatened by devil facial tumor disease (DFTD). While research on DFTD has been extensive, little is known about viruses in devils and whether any are of potential conservation relevance for this endangered species. Using both metagenomics based on virion enrichment and sequence-independent amplification (virion-enriched metagenomics) and metatranscriptomics based on bulk RNA sequencing, we characterized and compared the fecal viromes of captive and wild devils. A total of 54 fecal samples collected from two captive and four wild populations were processed for virome characterization using both approaches. In total, 24 novel marsupial-related viruses, comprising a sapelovirus, astroviruses, rotaviruses, picobirnaviruses, parvoviruses, papillomaviruses, polyomaviruses, and a gammaherpesvirus, were identified, as well as known mammalian pathogens such as rabbit hemorrhagic disease virus 2. Captive devils showed significantly lower viral diversity than wild devils. Comparison of the two virus discovery approaches revealed substantial differences in the number and types of viruses detected, with metatranscriptomics better suited for RNA viruses and virion-enriched metagenomics largely identifying more DNA viruses. Thus, the viral communities revealed by virion-enriched metagenomics and metatranscriptomics were not interchangeable and neither approach was able to detect all viruses present. An integrated approach using both virion-enriched metagenomics and metatranscriptomics constitutes a powerful tool for obtaining a complete overview of both the taxonomic and functional profiles of viral communities within a sample. IMPORTANCE The Tasmanian devil is an iconic Australian marsupial that has suffered an 80% population decline due to a contagious cancer, devil facial tumor disease, along with other threats. Until now, viral discovery in this species has been confined to one gammaherpesvirus (dasyurid herpesvirus 2 [DaHV-2]), for which captivity was identified as a significant risk factor. Our discovery of 24 novel marsupial-associated RNA and DNA viruses, and that viral diversity is lower in captive than in wild devils, has greatly expanded our knowledge of gut-associated viruses in devils and provides important baseline information that will contribute to the conservation and captive management of this endangered species. Our results also revealed that a combination of virion-enriched metagenomics and metatranscriptomics may be a more comprehensive approach for virome characterization than either method alone. Our results thus provide a springboard for continuous improvements in the way we study complex viral communities.",2019 May 15,"['Chong, Rowena', 'Shi, Mang', 'Grueber, Catherine E.', 'Holmes, Edward C.', 'Hogg, Carolyn J.', 'Belov, Katherine', 'Barrs, Vanessa R.']",J Virol,,,True
12f1cfc148951905b67370166c4b9ae8ee43d987,PMC,Fecal Viral Diversity of Captive and Wild Tasmanian Devils Characterized Using Virion-Enriched Metagenomics and Metatranscriptomics,http://dx.doi.org/10.1128/JVI.00205-19,PMC6532096,30867308,CC BY,"The Tasmanian devil is an endangered carnivorous marsupial threatened by devil facial tumor disease (DFTD). While research on DFTD has been extensive, little is known about viruses in devils and whether any are of potential conservation relevance for this endangered species. Using both metagenomics based on virion enrichment and sequence-independent amplification (virion-enriched metagenomics) and metatranscriptomics based on bulk RNA sequencing, we characterized and compared the fecal viromes of captive and wild devils. A total of 54 fecal samples collected from two captive and four wild populations were processed for virome characterization using both approaches. In total, 24 novel marsupial-related viruses, comprising a sapelovirus, astroviruses, rotaviruses, picobirnaviruses, parvoviruses, papillomaviruses, polyomaviruses, and a gammaherpesvirus, were identified, as well as known mammalian pathogens such as rabbit hemorrhagic disease virus 2. Captive devils showed significantly lower viral diversity than wild devils. Comparison of the two virus discovery approaches revealed substantial differences in the number and types of viruses detected, with metatranscriptomics better suited for RNA viruses and virion-enriched metagenomics largely identifying more DNA viruses. Thus, the viral communities revealed by virion-enriched metagenomics and metatranscriptomics were not interchangeable and neither approach was able to detect all viruses present. An integrated approach using both virion-enriched metagenomics and metatranscriptomics constitutes a powerful tool for obtaining a complete overview of both the taxonomic and functional profiles of viral communities within a sample. IMPORTANCE The Tasmanian devil is an iconic Australian marsupial that has suffered an 80% population decline due to a contagious cancer, devil facial tumor disease, along with other threats. Until now, viral discovery in this species has been confined to one gammaherpesvirus (dasyurid herpesvirus 2 [DaHV-2]), for which captivity was identified as a significant risk factor. Our discovery of 24 novel marsupial-associated RNA and DNA viruses, and that viral diversity is lower in captive than in wild devils, has greatly expanded our knowledge of gut-associated viruses in devils and provides important baseline information that will contribute to the conservation and captive management of this endangered species. Our results also revealed that a combination of virion-enriched metagenomics and metatranscriptomics may be a more comprehensive approach for virome characterization than either method alone. Our results thus provide a springboard for continuous improvements in the way we study complex viral communities.",2019 May 15,"['Chong, Rowena', 'Shi, Mang', 'Grueber, Catherine E.', 'Holmes, Edward C.', 'Hogg, Carolyn J.', 'Belov, Katherine', 'Barrs, Vanessa R.']",J Virol,,,False
fa0ea39aff2c19a92de12d6f0323721a9bfa38a8,PMC,Characterization of antiviral T cell responses during primary and secondary challenge of laboratory cats with feline infectious peritonitis virus (FIPV),http://dx.doi.org/10.1186/s12917-019-1909-6,PMC6532132,31118053,CC BY,"BACKGROUND: Feline infectious peritonitis (FIP) is considered highly fatal in its naturally occurring form, although up to 36% of cats resist disease after experimental infection, suggesting that cats in nature may also resist development of FIP in the face of infection with FIP virus (FIPV). Previous experimental FIPV infection studies suggested a role for cell-mediated immunity in resistance to development of FIP. This experimental FIPV infection study in specific pathogen free (SPF) kittens describes longitudinal antiviral T cell responses and clinical outcomes ranging from rapid progression, slow progression, and resistance to disease. RESULTS: Differences in disease outcome provided an opportunity to investigate the role of T cell immunity to FIP determined by T cell subset proliferation after stimulation with different viral antigens. Reduced total white blood cell (WBC), lymphocyte and T cell counts in blood were observed during primary acute infection for all experimental groups including cats that survived without clinical FIP. Antiviral T cell responses during early primary infection were also similar between cats that developed FIP and cats remaining healthy. Recovery of antiviral T cell responses during the later phase of acute infection was observed in a subset of cats that survived longer or resisted disease compared to cats showing rapid disease progression. More robust T cell responses at terminal time points were observed in lymph nodes compared to blood in cats that developed FIP. Cats that survived primary infection were challenged a second time to pathogenic FIPV and tested for antiviral T cell responses over a four week period. Nine of ten rechallenged cats did not develop FIP or T cell depletion and all cats demonstrated antiviral T cell responses at multiple time points after rechallenge. CONCLUSIONS: In summary, definitive adaptive T cell responses predictive of disease outcome were not detected during the early phase of primary FIPV infection. However emergence of antiviral T cell responses after a second exposure to FIPV, implicated cellular immunity in the control of FIPV infection and disease progression. Virus host interactions during very early stages of FIPV infection warrant further investigation to elucidate host resistance to FIP.",2019 May 22,"['Mustaffa-Kamal, Farina', 'Liu, Hongwei', 'Pedersen, Niels C.', 'Sparger, Ellen E.']",BMC Vet Res,,,True
43e0f5f9add9380a45d39f55aab2ca96d589280c,PMC,Arab world’s growing contribution to global leishmaniasis research (1998–2017): a bibliometric study,http://dx.doi.org/10.1186/s12889-019-6969-9,PMC6532175,31118003,CC BY,"BACKGROUND: Leishmaniasis is a parasitic disease caused by a protozoan of the Leishmania genus, and is considered a neglected tropical disease. It still remains a main public health concern at global level and in Arab world mainly in low-income countries. Therefore, this study was designed to evaluate the Arab world’s growing contribution to global leishmaniasis research. METHODS: This study describes a bibliometric review of all leishmaniasis research publications published between January 1998 and December 2017 indexed on the Scopus database. RESULTS: The total number of publications published at global level was 17,570 papers, which achieves an average annual productivity of 878.50 papers publications. Brazil was responsible for the greatest output with the total number of publications of 3865 followed by the Unites States (n = 2729), India (n = 2119), the United Kingdom (n = 1363), and Spain (n = 1274). By limiting the analysis to the publications that have been published by Arab world, the research productivity was 993 papers, which represents 5.65% of total research output at global level in research regarding leishmaniasis. Tunisia was responsible for the greatest output from Arab world with the total number of publications of 297 followed by Sudan (n = 192), Saudi Arabia (n = 131), Morocco (n = 119) and Egypt (n = 67). Since 1998, the growth of publications on leishmaniasis fluctuates, overall showing a rising trend in both global and Arab world. There is a highly significant correlation between publication productivity related to leishmaniasis at global level and the Arab world (r = 0.936; p-value< 0.001). Leishmaniasis treatment, intracellular mechanism of infection, and lifecycle of leishmania are the major current hot topics for the research in this subject at global level and the Arab world. CONCLUSIONS: The current study presents a novel review of the current Arab leishmaniasis-related research, and how these results are related to worldwide output. In comparison to the global research output, the Arab world produced less leishmaniasis research. The data presented in the current study by this innovative approach may serve relevant researchers to direct the global leishmaniasis research to Arab counties in which leishmaniasis is endemic.",2019 May 22,"Al-Jabi, Samah W.",BMC Public Health,,,True
26762988147d906e873f16c6e03cbb2ad7c46ea1,PMC,"Longitudinal study of humoral immunity to bovine coronavirus, virus shedding, and treatment for bovine respiratory disease in pre-weaned beef calves",http://dx.doi.org/10.1186/s12917-019-1887-8,PMC6532244,31118011,CC BY,"BACKGROUND: Bovine coronavirus (BCV) is associated with respiratory infections in cattle of all ages; however, a temporal study to evaluate the effect of BCV immunity on virus shedding and bovine respiratory disease (BRD) incidence in pre-weaned beef calves has not been reported. Thus, we report here a prospective study in three herds of crossbred beef calves (n = 817) with endemic BCV. Serial blood samples for measurement of serum anti-BCV antibody titers and nasal swabs for detection of BCV and other common viral and bacterial BRD pathogens were collected from all calves or subsets of calves at predetermined times from birth through weaning. The calves were monitored for BRD and those that developed signs of respiratory disease were sampled for diagnostic testing. To discover additional risk factors that could have influenced BRD development, sequence analysis of the BCV strain(s) circulating in each herd, and the prevalence of common opportunistic bacterial pathogens in the upper respiratory tract of sick and apparently healthy cattle were also evaluated. RESULTS: Two hundred forty-eight of the 817 study calves (30.4%) were treated for BRD prior to weaning; 246 of those were from a single herd involved in two outbreaks of BRD leading to mass treatment of all calves in that group. Molecular diagnostic testing found BCV and Histophilus somni in nasal swabs taken at the time of BRD treatment. Between herd analyses revealed anti-BCV serum antibody abundance did not associate with the incidence of BRD or BCV shedding, though these measurements may have been hindered by the long periods between sample collections. Analysis of the BCV spike gene hypervariable region revealed four polymorphisms in 15 isolates from the three herds, making strain variation unlikely to account for differences in treatment rates between herds. Persistent or recurrent shedding episodes of BCV occurred in some animals treated for BRD. CONCLUSION: Co-detection of BCV and H. somni at the time of the disease outbreak suggests that these pathogens contributed to disease pathogenesis. Developing appropriate control measures for respiratory BCV infections may help decrease the incidence of pre-weaning BRD. The role of antibodies in protection must still be further defined. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-019-1887-8) contains supplementary material, which is available to authorized users.",2019 May 22,"['Workman, Aspen M.', 'Kuehn, Larry A.', 'McDaneld, Tara G.', 'Clawson, Michael L.', 'Loy, John Dustin']",BMC Vet Res,,,True
07177128e49e7d7440cebca1eb70294a3fc27cbb,PMC,Healthcare-Associated Pneumonia: Don't Forget About Respiratory Viruses!,http://dx.doi.org/10.3389/fped.2019.00168,PMC6532533,31157191,CC BY,"Introduction: Healthcare-associated infections are an important cause of morbidity and mortality, are among the most common adverse events in healthcare, and of them, pneumonia is the most commonly reported. Our objective was to evaluate the incidence and clinical outcome of respiratory viruses in hospital-acquired pneumonia (HAP). Methods: This was a prospective cohort study, include patients aged between 0 and 18 who fulfilled Centers for Diseases Control and Prevention (CDC) criteria for HAP. Demographic and clinical data were obtained, and a nasopharyngeal swab specimen was taken for the detection of respiratory viruses. All included patients were monitored until discharge to collect data on the need for mechanical ventilation, intensive care unit (ICU) admission, and mortality. All-cause 30-day mortality was also ascertained. Results: Four thousand three hundred twenty-seven patients were followed for 42,658 patient-days and 5,150 ventilator-days. Eighty-eight patients (2.03%) met the CDC criteria for HAP, 63 patients were included, and clinical and epidemiological characteristics showed no statistically significant differences between patients with virus associated healthcare-associated pneumonia (VAHAP) and those with non-viral healthcare-associated pneumonia (NVHAP). At least one respiratory virus was detected in 65% [95% CI (53–77)] of episodes of HAP, with a single viral pathogen observed in 53.9% and coinfection with 2 viruses in 11.1% of cases. The outcome in terms of ICU admission, mechanical ventilation and the 30-day mortality did not show a significant difference between groups. Conclusions: In two-thirds of the patients a respiratory virus was identified. There was no difference in mortality or the rest of the clinical outcome variables. About half of the patients required mechanical ventilation and 10% died, which emphasizes the importance of considering these pathogens in nosocomial infections, since their identification can influence the decrease in hospital costs and be taken into account in infection control policies.",2019 May 16,"['Torres-García, Margarita', 'Pérez Méndez, Brenda Berenice', 'Sánchez Huerta, José Luis', 'Villa Guillén, Mónica', 'Rementería Vazquez, Virydiana', 'Castro Diaz, Arturo Daniel', 'López Martinez, Briceida', 'Laris González, Almudena', 'Jiménez-Juárez, Rodolfo Norberto', 'de la Rosa-Zamboni, Daniela']",Front Pediatr,,,True
3650642872361a257da4f4bd3038e38eabe7019d,PMC,The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template,http://dx.doi.org/10.1016/j.celrep.2019.04.082,PMC6533203,31116986,CC BY,"Epitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization. A chimpanzee simian immunodeficiency virus (SIV) envelope (Env) shares a single bnAb site, the variable loop 2 (V2)-apex, with HIV, suggesting its possible utility in an HIV immunization strategy. Here, we generate a chimpanzee SIV Env trimer, MT145K, which displays selective binding to HIV V2-apex bnAbs and precursor versions, but no binding to other HIV specificities. We determine the structure of the MT145K trimer by cryo-EM and show that its architecture is remarkably similar to HIV Env. Immunization of an HIV V2-apex bnAb precursor Ab-expressing knockin mouse with the chimpanzee MT145K trimer induces HIV V2-specific neutralizing responses. Subsequent boosting with an HIV trimer cocktail induces responses that exhibit some virus cross-neutralization. Overall, the chimpanzee MT145K trimer behaves as expected from design both in vitro and in vivo and is an attractive potential component of a sequential immunization regimen to induce V2-apex bnAbs.",2019 May 21,"['Andrabi, Raiees', 'Pallesen, Jesper', 'Allen, Joel D.', 'Song, Ge', 'Zhang, Jinsong', 'de Val, Natalia', 'Gegg, Gavin', 'Porter, Katelyn', 'Su, Ching-Yao', 'Pauthner, Matthias', 'Newman, Amanda', 'Bouton-Verville, Hilary', 'Garces, Fernando', 'Wilson, Ian A.', 'Crispin, Max', 'Hahn, Beatrice H.', 'Haynes, Barton F.', 'Verkoczy, Laurent', 'Ward, Andrew B.', 'Burton, Dennis R.']",Cell Rep,,,False
3e33a3ac043599234aec183191db2c3b9a2b7970,PMC,The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template,http://dx.doi.org/10.1016/j.celrep.2019.04.082,PMC6533203,31116986,CC BY,"Epitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization. A chimpanzee simian immunodeficiency virus (SIV) envelope (Env) shares a single bnAb site, the variable loop 2 (V2)-apex, with HIV, suggesting its possible utility in an HIV immunization strategy. Here, we generate a chimpanzee SIV Env trimer, MT145K, which displays selective binding to HIV V2-apex bnAbs and precursor versions, but no binding to other HIV specificities. We determine the structure of the MT145K trimer by cryo-EM and show that its architecture is remarkably similar to HIV Env. Immunization of an HIV V2-apex bnAb precursor Ab-expressing knockin mouse with the chimpanzee MT145K trimer induces HIV V2-specific neutralizing responses. Subsequent boosting with an HIV trimer cocktail induces responses that exhibit some virus cross-neutralization. Overall, the chimpanzee MT145K trimer behaves as expected from design both in vitro and in vivo and is an attractive potential component of a sequential immunization regimen to induce V2-apex bnAbs.",2019 May 21,"['Andrabi, Raiees', 'Pallesen, Jesper', 'Allen, Joel D.', 'Song, Ge', 'Zhang, Jinsong', 'de Val, Natalia', 'Gegg, Gavin', 'Porter, Katelyn', 'Su, Ching-Yao', 'Pauthner, Matthias', 'Newman, Amanda', 'Bouton-Verville, Hilary', 'Garces, Fernando', 'Wilson, Ian A.', 'Crispin, Max', 'Hahn, Beatrice H.', 'Haynes, Barton F.', 'Verkoczy, Laurent', 'Ward, Andrew B.', 'Burton, Dennis R.']",Cell Rep,,,False
0dbc8dd1c306474ee5d560eaab38a9500bceb7d9,PMC,The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template,http://dx.doi.org/10.1016/j.celrep.2019.04.082,PMC6533203,31116986,CC BY,"Epitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization. A chimpanzee simian immunodeficiency virus (SIV) envelope (Env) shares a single bnAb site, the variable loop 2 (V2)-apex, with HIV, suggesting its possible utility in an HIV immunization strategy. Here, we generate a chimpanzee SIV Env trimer, MT145K, which displays selective binding to HIV V2-apex bnAbs and precursor versions, but no binding to other HIV specificities. We determine the structure of the MT145K trimer by cryo-EM and show that its architecture is remarkably similar to HIV Env. Immunization of an HIV V2-apex bnAb precursor Ab-expressing knockin mouse with the chimpanzee MT145K trimer induces HIV V2-specific neutralizing responses. Subsequent boosting with an HIV trimer cocktail induces responses that exhibit some virus cross-neutralization. Overall, the chimpanzee MT145K trimer behaves as expected from design both in vitro and in vivo and is an attractive potential component of a sequential immunization regimen to induce V2-apex bnAbs.",2019 May 21,"['Andrabi, Raiees', 'Pallesen, Jesper', 'Allen, Joel D.', 'Song, Ge', 'Zhang, Jinsong', 'de Val, Natalia', 'Gegg, Gavin', 'Porter, Katelyn', 'Su, Ching-Yao', 'Pauthner, Matthias', 'Newman, Amanda', 'Bouton-Verville, Hilary', 'Garces, Fernando', 'Wilson, Ian A.', 'Crispin, Max', 'Hahn, Beatrice H.', 'Haynes, Barton F.', 'Verkoczy, Laurent', 'Ward, Andrew B.', 'Burton, Dennis R.']",Cell Rep,,,True
d8e134d93a4666285518b7916316a97dcc258788,PMC,Vesicular Stomatitis Virus-Based Vaccine Protects Mice against Crimean-Congo Hemorrhagic Fever,http://dx.doi.org/10.1038/s41598-019-44210-6,PMC6533279,31123310,CC BY,"Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne bunyavirus, can cause a life-threatening hemorrhagic syndrome in humans but not in its animal host. The virus is widely distributed throughout southeastern Europe, the Middle East, Africa, and Asia. Disease management has proven difficult and there are no broadly licensed vaccines or therapeutics. Recombinant vesicular stomatitis viruses (rVSV) expressing foreign glycoproteins (GP) have shown promise as experimental vaccines for several viral hemorrhagic fevers. Here, we developed and assessed a replication competent rVSV vector expressing the CCHFV glycoprotein precursor (GPC), which encodes CCHFV structural glycoproteins. This construct drives strong expression of CCHFV-GP, in vitro. Using these vectors, we vaccinated STAT-1 knock-out mice, an animal model for CCHFV. The vector was tolerated and 100% efficacious against challenge from a clinical strain of CCHFV. Anti-CCHFV-GP IgG and neutralizing antibody titers were observed in surviving animals. This study demonstrates that a rVSV expressing only the CCHFV-GP has the potential to serve as a replication competent vaccine platform against CCHF infections.",2019 May 23,"['Rodriguez, Sergio E.', 'Cross, Robert W.', 'Fenton, Karla A.', 'Bente, Dennis A.', 'Mire, Chad E.', 'Geisbert, Thomas W.']",Sci Rep,,,True
12127085d9546a704eb677320d4df5b44f4dce8f,PMC,Uganda public health fellowship program’s contribution to building a resilient and sustainable public health system in Uganda,http://dx.doi.org/10.1080/16549716.2019.1609825,PMC6534252,31117889,CC BY,"Background: Low-income countries with relatively weak-health systems are highly vulnerable to public health threats. Effective public health system with a workforce to investigate outbreaks can reduce disease impact on livelihoods and economic development. Building effective public health partnerships is critical for sustainability of such a system. Uganda has made significant progress in responding to emergencies during the past quarter century, but its public health workforce is still inadequate in number and competency. Objectives: To reinforce implementation of priority public health programs in Uganda and cultivate core capacities for compliance with International Health Regulations. Methods: To develop a competent workforce to manage epidemics and improve disease surveillance, Uganda Ministry of Health (MoH) established an advanced-level Field Epidemiology Training Program, called Public Health Fellowship Program (PHFP); closely modelled after the US CDC’s Epidemic Intelligence Service. PHFP is a 2-year, full-time, non-degree granting program targeting mid-career public health professionals. Fellows spend 85% of their field time in MoH placements learning through service delivery and gaining competencies in major domains. Results: During 2015–2018, PHFP enrolled 41 fellows, and graduated 30. Fellows were placed in 19 priority areas at MoH and completed 235 projects (91 outbreaks, 12 refugee assessments, 50 surveillance, and 60 epidemiologic studies, 3 cost analysis and 18 quality improvement); made 194 conference presentations; prepared 63 manuscripts for peer-reviewed publications (27 published as of December 2018); produced MoH bulletins, and developed three case studies. Projects have resulted in public health interventions with improvements in surveillance systems and disease control. Conclusion: During the 4 years of existence, PHFP has contributed greatly to improving real-time disease surveillance and outbreak response core capacities. Enhanced focus on evidence-based targeted approaches has increased effectiveness in outbreak response and control, and integration of PHFP within MoH has contributed to building a resilient and sustainable health system in Uganda.",2019 May 23,"['Ario, Alex Riolexus', 'Bulage, Lilian', 'Kadobera, Daniel', 'Kwesiga, Benon', 'Kabwama, Steven N.', 'Tusiime, Patrick', 'Wanyenze, Rhoda K.']",Glob Health Action,,,True
2d73c30f41bb0fd24d5ddf1e71a472d971ce4d6f,PMC,Bactrian camels shed large quantities of Middle East respiratory syndrome coronavirus (MERS-CoV) after experimental infection,http://dx.doi.org/10.1080/22221751.2019.1618687,PMC6534258,31119984,CC BY,"In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) emerged. To date, more than 2300 cases have been reported, with an approximate case fatality rate of 35%. Epidemiological investigations identified dromedary camels as the source of MERS-CoV zoonotic transmission and evidence of MERS-CoV circulation has been observed throughout the original range of distribution. Other new-world camelids, alpacas and llamas, are also susceptible to MERS-CoV infection. Currently, it is unknown whether Bactrian camels are susceptible to infection. The distribution of Bactrian camels overlaps partly with that of the dromedary camel in west and central Asia. The receptor for MERS-CoV, DPP4, of the Bactrian camel was 98.3% identical to the dromedary camel DPP4, and 100% identical for the 14 residues which interact with the MERS-CoV spike receptor. Upon intranasal inoculation with 107 plaque-forming units of MERS-CoV, animals developed a transient, primarily upper respiratory tract infection. Clinical signs of the MERS-CoV infection were benign, but shedding of large quantities of MERS-CoV from the URT was observed. These data are similar to infections reported with dromedary camel infections and indicate that Bactrians are susceptible to MERS-CoV and given their overlapping range are at risk of introduction and establishment of MERS-CoV within the Bactrian camel populations.",2019 May 23,"['Adney, Danielle R.', 'Letko, Michael', 'Ragan, Izabela K.', 'Scott, Dana', 'van Doremalen, Neeltje', 'Bowen, Richard A.', 'Munster, Vincent J.']",Emerg Microbes Infect,,,True
35229a458e5e6c73b9bcc155eedb15c62a24ce17,PMC,A Novel Questionnaire to Ergonomically Assess Respirators among Health Care Staff: Development and Validation,,PMC6534796,31143216,CC BY,"BACKGROUND: Health care workers are at a high risk of exposure to infectious diseases spread by airborne transmission. N95 respirators are the most common respirators used in the health care system and negligence in using them may cause health problems. Hence, more emphasis should be on ergonomic aspects of this mask. This study aimed to develop a tool for ergonomic evaluation of these respirators. MATERIALS AND METHODS: After reviewing previous studies and employees’ problems in the use of the N95 respirators, 50 questionnaires were designed and their validity was assessed. Then, the questionnaire was completed by 290 staff members of Masih Daneshvari Hospital and its internal consistency and reproducibility were investigated using Cronbach’s alpha coefficient and test-retest method, respectively. Confirmatory factor analysis was used to assess its consistency and internal consistency (construct validity). RESULTS: With the confirmation of the face and content validities, internal consistency (0.89) calculated by the Cronbach’s alpha coefficient and reproducibility of the questionnaire (0.997; p<0.001) assessed by using the ICC Index, were approved. Following examining internal consistency and stability, the questionnaire convergent construct validity was also confirmed using confirmatory factor analysis. CONCLUSION: The questionnaire contained 42 items and it is beneficial to use it in the health care system to evaluate the ergonomic problems of the respirators and to have optimal choice in this respect. Also, it can be used in the promotion of the staffs’ behavior in wearing these respirators when necessary.",2018 Oct,"['Jazani, Reza Khani', 'Seyedmehdi, Seyed Mohammad', 'Kavousi, Amir', 'Javazm, Somaye Tahernezhad']",Tanaffos,,,True
703b5f4019a1c215901309bcabddba33738c506a,PMC,Development and evaluation of a real-time RT-PCR and a field-deployable RT-insulated isothermal PCR for the detection of Seneca Valley virus,http://dx.doi.org/10.1186/s12917-019-1927-4,PMC6534938,31126297,CC BY,"BACKGROUND: Seneca Valley virus (SVV) has emerged in multiple countries in recent years. SVV infection can cause vesicular lesions clinically indistinguishable from those caused by other vesicular disease viruses, such as foot-and-mouth disease virus (FMDV), swine vesicular disease virus (SVDV), vesicular stomatitis virus (VSV), and vesicular exanthema of swine virus (VESV). Sensitive and specific RT-PCR assays for the SVV detection is necessary for differential diagnosis. Real-time RT-PCR (rRT-PCR) has been used for the detection of many RNA viruses. The insulated isothermal PCR (iiPCR) on a portable POCKIT™ device is user friendly for on-site pathogen detection. In the present study, SVV rRT-PCR and RT-iiPCR were developed and validated. RESULTS: Neither the SVV rRT-PCR nor the RT-iiPCR cross-reacted with any of the vesicular disease viruses (20 FMDV, two SVDV, six VSV, and two VESV strains), classical swine fever virus (four strains), and 15 other common swine viruses. Analytical sensitivities of the SVV rRT-PCR and RT-iiPCR were determined using serial dilutions of in vitro transcribed RNA as well as viral RNA extracted from a historical SVV isolate and a contemporary SVV isolate. Diagnostic performances were further evaluated using 125 swine samples by two approaches. First, nucleic acids were extracted from the 125 samples using the MagMAX™ kit and then tested by both RT-PCR methods. One sample was negative by the rRT-PCR but positive by the RT-iiPCR, resulting in a 99.20% agreement (124/125; 95% CI: 96.59–100%, κ = 0.98). Second, the 125 samples were tested by the taco™ mini extraction/RT-iiPCR and by the MagMAX™ extraction/rRT-PCR system in parallel. Two samples were positive by the MagMAX™/rRT-PCR system but negative by the taco™ mini/RT-iiPCR system, resulting in a 98.40% agreement (123/125; 95% CI: 95.39–100%, κ = 0.97). The two samples with discrepant results had relatively high C(T) values. CONCLUSIONS: The SVV rRT-PCR and RT-iiPCR developed in this study are very sensitive and specific and have comparable diagnostic performances for SVV RNA detection. The SVV rRT-PCR can be adopted for SVV detection in laboratories. The SVV RT-iiPCR in a simple field-deployable system could serve as a tool to help diagnose vesicular diseases in swine at points of need.",2019 May 24,"['Zhang, Jianqiang', 'Nfon, Charles', 'Tsai, Chuan-Fu', 'Lee, Chien-Hsien', 'Fredericks, Lindsay', 'Chen, Qi', 'Sinha, Avanti', 'Bade, Sarah', 'Harmon, Karen', 'Piñeyro, Pablo', 'Gauger, Phillip', 'Tsai, Yun-Long', 'Wang, Hwa-Tang Thomas', 'Lee, Pei-Yu Alison']",BMC Vet Res,,,True
e423977e8070a5037558ac9dfdd78a6db6a64d58,PMC,Immunomodulatory Effect after Irreversible Electroporation in Patients with Locally Advanced Pancreatic Cancer,http://dx.doi.org/10.1155/2019/9346017,PMC6535893,31214261,CC BY,"PURPOSE: Irreversible electroporation (IRE) has been demonstrated to be a safe and effective method for locally advanced pancreatic cancer (LAPC). The aim of this study was to evaluate the immunomodulatory effect after IRE and to evaluate the prognostic value of variations of the immune parameters in LAPC patients after IRE. METHODS: Peripheral blood samples of 34 patients were obtained preoperatively and on the third day (D3) and seventh day (D7) after IRE, respectively. The phenotypes of lymphocytes were analyzed by flow cytometry, and dynamic changes of serum levels of cytokines, complement, and immunoglobulin were assayed by enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curve and concordance index (C-index) were used to compare the survival predictive ability. RESULTS: There was a transitory decrease followed by a steady increase for CD4(+) T cell, CD8(+) T cell, NK cell, IL-2, C3, C4, and IgG while a reverse trend was detected for Treg cell, IL-6, and IL10 after IRE. The alteration of CD8(+) T cell between D3 and D7 was identified as a prognostic factor for both overall survival (OS) and progression-free survival (PFS). The values of ROC curve (AUC) and C-indexes of the alteration of CD8(+) T cell for OS and PFS were 0.816 and 0.773 and 0.816 and 0.639, respectively, which were larger than those of other immune or inflammation-based indexes. CONCLUSIONS: This study presented the first evidence of IRE-based immunomodulatory in patients with LAPC. The alteration of CD8(+) T cell between D3 and D7 showed relatively good performance and could be used as an effective tool for prognostic evaluation for LAPC patients after IRE.",2019 May 12,"['He, Chaobin', 'Wang, Jun', 'Sun, Shuxin', 'Zhang, Yu', 'Li, Shengping']",J Oncol,,,True
cdf9d4e00e66bd0c1751c1cc41ec13d0baed9749,PMC,Global status of Middle East respiratory syndrome coronavirus in dromedary camels: a systematic review – CORRIGENDUM,http://dx.doi.org/10.1017/S0950268819000669,PMC6536756,31364519,CC BY,,2019 May 17,"['Sikkema, R. S.', 'Farag, E. A. B. A.', 'Islam, Mazharul', 'Atta, Muzzamil', 'Reusken, C. B. E. M.', 'Al-Hajri, Mohd M.', 'Koopmans, M. P. G.']",Epidemiol Infect,,,True
0cf9f507a18a00de76b8bb61a2c5c2b66680dd50,PMC,Coronavirus envelope protein: current knowledge,http://dx.doi.org/10.1186/s12985-019-1182-0,PMC6537279,31133031,CC BY,"BACKGROUND: Coronaviruses (CoVs) primarily cause enzootic infections in birds and mammals but, in the last few decades, have shown to be capable of infecting humans as well. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and, more recently, Middle-East respiratory syndrome (MERS) has demonstrated the lethality of CoVs when they cross the species barrier and infect humans. A renewed interest in coronaviral research has led to the discovery of several novel human CoVs and since then much progress has been made in understanding the CoV life cycle. The CoV envelope (E) protein is a small, integral membrane protein involved in several aspects of the virus’ life cycle, such as assembly, budding, envelope formation, and pathogenesis. Recent studies have expanded on its structural motifs and topology, its functions as an ion-channelling viroporin, and its interactions with both other CoV proteins and host cell proteins. MAIN BODY: This review aims to establish the current knowledge on CoV E by highlighting the recent progress that has been made and comparing it to previous knowledge. It also compares E to other viral proteins of a similar nature to speculate the relevance of these new findings. Good progress has been made but much still remains unknown and this review has identified some gaps in the current knowledge and made suggestions for consideration in future research. CONCLUSIONS: The most progress has been made on SARS-CoV E, highlighting specific structural requirements for its functions in the CoV life cycle as well as mechanisms behind its pathogenesis. Data shows that E is involved in critical aspects of the viral life cycle and that CoVs lacking E make promising vaccine candidates. The high mortality rate of certain CoVs, along with their ease of transmission, underpins the need for more research into CoV molecular biology which can aid in the production of effective anti-coronaviral agents for both human CoVs and enzootic CoVs.",2019 May 27,"['Schoeman, Dewald', 'Fielding, Burtram C.']",Virol J,,,True
4c53844f8deb79b66a4dd8b5a8c47654b0d4d7ec,PMC,The 2017 Oslo conference report on neglected tropical diseases and emerging/re-emerging infectious diseases – focus on populations underserved,http://dx.doi.org/10.1186/s40249-019-0550-8,PMC6537383,31138293,CC BY,"BACKGROUND: In 2017, the Centre for Global Health (CGH) at the University of Oslo in collaboration with the Coalition for Epidemic Preparedness Innovations (CEPI) and the Norwegian Agency for Development Cooperation (Norad) held a meeting to discuss together with leading figures in disease control, research and development the issue of neglected tropical diseases and emerging/re-emerging infectious diseases. This commentary has taken up this discussion and the conclusions drawn at this meeting to make a case for the opportunity the Sustainable Development Goals (SDGs) provide in highlighting the interconnectedness of factors that are relevant in the successful fight against neglected tropical diseases (NTDs) and emerging infectious diseases (EIDS). MAIN BODY: Despite NTDs being endemic and EIDS being epidemic, in order to prevent both disease groups effectively, it is important to appreciate that they share essential health determining factors, namely: neglect, poverty, a lack of access to clean water and sanitation facilities and an absence of or severely limited provision of healthcare as well as in many cases a zoonotic nature. Instead of looking to “simple disease management” for the answer, the SDGs help to understand the interplay of multiple priority areas and thereby help to promote a more holistic approach to addressing these two disease groups. CONCLUSIONS: Their commonalities mean that the Global Health community should leverage opportunities and efforts in the prevention and elimination of both NTDs and EIDs. Doing so using a One Health approach is considered to offer a “public health best-buy”. Concrete solutions are proposed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-019-0550-8) contains supplementary material, which is available to authorized users.",2019 May 28,"['Klohe, Katharina', 'Amuasi, John', 'Kaducu, Joyce Moriku', 'Haavardsson, Ingeborg', 'Bogatyreva, Ekaterina', 'Onarheim, Kristine Husøy', 'Harrison, Wendy', 'Kristensen, Frederik', 'Prazeres da Costa, Clarissa', 'Winkler, Andrea S.']",Infect Dis Poverty,,,False
4541100142ffce230655e3b7c3ee2f63173a147c,PMC,The 2017 Oslo conference report on neglected tropical diseases and emerging/re-emerging infectious diseases – focus on populations underserved,http://dx.doi.org/10.1186/s40249-019-0550-8,PMC6537383,31138293,CC BY,"BACKGROUND: In 2017, the Centre for Global Health (CGH) at the University of Oslo in collaboration with the Coalition for Epidemic Preparedness Innovations (CEPI) and the Norwegian Agency for Development Cooperation (Norad) held a meeting to discuss together with leading figures in disease control, research and development the issue of neglected tropical diseases and emerging/re-emerging infectious diseases. This commentary has taken up this discussion and the conclusions drawn at this meeting to make a case for the opportunity the Sustainable Development Goals (SDGs) provide in highlighting the interconnectedness of factors that are relevant in the successful fight against neglected tropical diseases (NTDs) and emerging infectious diseases (EIDS). MAIN BODY: Despite NTDs being endemic and EIDS being epidemic, in order to prevent both disease groups effectively, it is important to appreciate that they share essential health determining factors, namely: neglect, poverty, a lack of access to clean water and sanitation facilities and an absence of or severely limited provision of healthcare as well as in many cases a zoonotic nature. Instead of looking to “simple disease management” for the answer, the SDGs help to understand the interplay of multiple priority areas and thereby help to promote a more holistic approach to addressing these two disease groups. CONCLUSIONS: Their commonalities mean that the Global Health community should leverage opportunities and efforts in the prevention and elimination of both NTDs and EIDs. Doing so using a One Health approach is considered to offer a “public health best-buy”. Concrete solutions are proposed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-019-0550-8) contains supplementary material, which is available to authorized users.",2019 May 28,"['Klohe, Katharina', 'Amuasi, John', 'Kaducu, Joyce Moriku', 'Haavardsson, Ingeborg', 'Bogatyreva, Ekaterina', 'Onarheim, Kristine Husøy', 'Harrison, Wendy', 'Kristensen, Frederik', 'Prazeres da Costa, Clarissa', 'Winkler, Andrea S.']",Infect Dis Poverty,,,True
8c6c9ecd42db747819abdedb3144a2b0a8ad027a,PMC,Chemical screen identifies a geroprotective role of quercetin in premature aging,http://dx.doi.org/10.1007/s13238-018-0567-y,PMC6538594,30069858,CC BY,"Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13238-018-0567-y) contains supplementary material, which is available to authorized users.",2019 Jun 1,"['Geng, Lingling', 'Liu, Zunpeng', 'Zhang, Weiqi', 'Li, Wei', 'Wu, Zeming', 'Wang, Wei', 'Ren, Ruotong', 'Su, Yao', 'Wang, Peichang', 'Sun, Liang', 'Ju, Zhenyu', 'Chan, Piu', 'Song, Moshi', 'Qu, Jing', 'Liu, Guang-Hui']",Protein Cell,,,False
7cc4fbbb0881277449c41f6f408fab4fb9b907f5,PMC,Chemical screen identifies a geroprotective role of quercetin in premature aging,http://dx.doi.org/10.1007/s13238-018-0567-y,PMC6538594,30069858,CC BY,"Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13238-018-0567-y) contains supplementary material, which is available to authorized users.",2019 Jun 1,"['Geng, Lingling', 'Liu, Zunpeng', 'Zhang, Weiqi', 'Li, Wei', 'Wu, Zeming', 'Wang, Wei', 'Ren, Ruotong', 'Su, Yao', 'Wang, Peichang', 'Sun, Liang', 'Ju, Zhenyu', 'Chan, Piu', 'Song, Moshi', 'Qu, Jing', 'Liu, Guang-Hui']",Protein Cell,,,True
50c63f3bfae37dbb495ef4d69b0d68c5c42b49ce,PMC,Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors,http://dx.doi.org/10.1038/s41467-019-10280-3,PMC6538669,31138817,CC BY,"Recent history is punctuated by the emergence of highly pathogenic coronaviruses such as SARS- and MERS-CoV into human circulation. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Here, we present the 3.1 Å resolution structure of the SARS-CoV nsp12 polymerase bound to its essential co-factors, nsp7 and nsp8, using single particle cryo-electron microscopy. nsp12 possesses an architecture common to all viral polymerases as well as a large N-terminal extension containing a kinase-like fold and is bound by two nsp8 co-factors. This structure illuminates the assembly of the coronavirus core RNA-synthesis machinery, provides key insights into nsp12 polymerase catalysis and fidelity and acts as a template for the design of novel antiviral therapeutics.",2019 May 28,"['Kirchdoerfer, Robert N.', 'Ward, Andrew B.']",Nat Commun,,,True
204b918c9054583e3887f03b5ddf5407bd4a5a60,PMC,Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors,http://dx.doi.org/10.1038/s41467-019-10280-3,PMC6538669,31138817,CC BY,"Recent history is punctuated by the emergence of highly pathogenic coronaviruses such as SARS- and MERS-CoV into human circulation. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Here, we present the 3.1 Å resolution structure of the SARS-CoV nsp12 polymerase bound to its essential co-factors, nsp7 and nsp8, using single particle cryo-electron microscopy. nsp12 possesses an architecture common to all viral polymerases as well as a large N-terminal extension containing a kinase-like fold and is bound by two nsp8 co-factors. This structure illuminates the assembly of the coronavirus core RNA-synthesis machinery, provides key insights into nsp12 polymerase catalysis and fidelity and acts as a template for the design of novel antiviral therapeutics.",2019 May 28,"['Kirchdoerfer, Robert N.', 'Ward, Andrew B.']",Nat Commun,,,False
ec9b3796e6bde50359a5cc5d7bff0060696feafe,PMC,Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors,http://dx.doi.org/10.1038/s41467-019-10280-3,PMC6538669,31138817,CC BY,"Recent history is punctuated by the emergence of highly pathogenic coronaviruses such as SARS- and MERS-CoV into human circulation. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Here, we present the 3.1 Å resolution structure of the SARS-CoV nsp12 polymerase bound to its essential co-factors, nsp7 and nsp8, using single particle cryo-electron microscopy. nsp12 possesses an architecture common to all viral polymerases as well as a large N-terminal extension containing a kinase-like fold and is bound by two nsp8 co-factors. This structure illuminates the assembly of the coronavirus core RNA-synthesis machinery, provides key insights into nsp12 polymerase catalysis and fidelity and acts as a template for the design of novel antiviral therapeutics.",2019 May 28,"['Kirchdoerfer, Robert N.', 'Ward, Andrew B.']",Nat Commun,,,False
7fd0972f4d5eb0e4c7ec68efad48fc01a1f547c2,PMC,Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors,http://dx.doi.org/10.1038/s41467-019-10280-3,PMC6538669,31138817,CC BY,"Recent history is punctuated by the emergence of highly pathogenic coronaviruses such as SARS- and MERS-CoV into human circulation. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Here, we present the 3.1 Å resolution structure of the SARS-CoV nsp12 polymerase bound to its essential co-factors, nsp7 and nsp8, using single particle cryo-electron microscopy. nsp12 possesses an architecture common to all viral polymerases as well as a large N-terminal extension containing a kinase-like fold and is bound by two nsp8 co-factors. This structure illuminates the assembly of the coronavirus core RNA-synthesis machinery, provides key insights into nsp12 polymerase catalysis and fidelity and acts as a template for the design of novel antiviral therapeutics.",2019 May 28,"['Kirchdoerfer, Robert N.', 'Ward, Andrew B.']",Nat Commun,,,True
04e314a46a06814267d29c2e6dfc00bf4121cc94,PMC,Flavivirus Replication Organelle Biogenesis in the Endoplasmic Reticulum: Comparison with Other Single-Stranded Positive-Sense RNA Viruses,http://dx.doi.org/10.3390/ijms20092336,PMC6539296,31083507,CC BY,"Some single-stranded positive-sense RNA [ssRNA(+)] viruses, including Flavivirus, generate specific organelle-like structures in the host endoplasmic reticulum (ER). These structures are called virus replication organelles and consist of two distinct subdomains, the vesicle packets (VPs) and the convoluted membranes (CMs). The VPs are clusters of small vesicle compartments and are considered to be the site of viral genome replication. The CMs are electron-dense amorphous structures observed in proximity to the VPs, but the exact roles of CMs are mostly unknown. Several recent studies have revealed that flaviviruses recruit several host factors that are usually used for the biogenesis of other conventional organelles and usurp their function to generate virus replication organelles. In the current review, we summarize recent studies focusing on the role of host factors in the formation of virus replication organelles and discuss how these intricate membrane structures are organized.",2019 May 11,"['Arakawa, Masashi', 'Morita, Eiji']",Int J Mol Sci,,,True
93aab5344693c6df1630f5dcd54b16ad82d7966a,PMC,In Vitro and in Vivo Antiviral Activity of Mizoribine Against Foot-And-Mouth Disease Virus,http://dx.doi.org/10.3390/molecules24091723,PMC6539406,31058822,CC BY,"Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals, which has significant economic consequences in affected countries. As the currently available vaccines against FMD provide no protection until 4–7 days post-vaccination, the only alternative method to control the spread of FMD virus (FMDV) during outbreaks is the application of antiviral agents. Hence, it is important to identify effective antiviral agents against FMDV infection. In this study, we found that mizoribine has potent antiviral activity against FMDV replication in IBRS-2 cells. A time-of-drug-addition assay demonstrated that mizoribine functions at the early stage of replication. Moreover, mizoribine also showed antiviral effect on FMDV in vivo. In summary, these results revealed that mizoribine could be a potential antiviral drug against FMDV.",2019 May 3,"['Li, Shi-Fang', 'Gong, Mei-Jiao', 'Sun, Yue-Feng', 'Shao, Jun-Jun', 'Zhang, Yong-Guang', 'Chang, Hui-Yun']",Molecules,,,True
f81e9eb1b488b5a21f7bfbe5ece67dbd80425f86,PMC,A Novel Immunochromatographic Strip for Antigen Detection of Avian Infectious Bronchitis Virus,http://dx.doi.org/10.3390/ijms20092216,PMC6540333,31064083,CC BY,"Avian infectious bronchitis virus (IBV) causes considerable economic losses in the poultry industry worldwide, including Taiwan. IBV is among the most important pathogens in chickens, and it spreads rapidly among flocks. In addition to dozens of known serotypes, new viral variants have emerged due to the viral evolution and antigenic variation in IBVs. Therefore, the development of a sensitive, specific, and easily performed assay is crucial for the rapid detection and surveillance of IBV infections. A rapid and simple immunochromatographic strip (ICS) was developed in this study by employing monoclonal antibodies against spike and nucleocapsid proteins of IBV as the tracer and the capture antibody. The ICS showed high specificity in detecting IBV antigens, including several IBV genotypes and novel variants, as opposed to three other common avian respiratory viruses. The detection limit of the strip reached 10(4.4) 50% embryo-infective dose. Moreover, in the experimental chicken model, the strip test demonstrated consistency in detecting IBV with RT-PCR gene detection. Taken together, this antigen detection strip has the potential to serve as an on-farm rapid test for IBV; therefore, it may facilitate surveillance and control of the disease.",2019 May 6,"['Liu, I-Li', 'Lin, Yi-Chun', 'Lin, Yong-Chong', 'Jian, Cai-Zhen', 'Cheng, Ivan-Chen', 'Chen, Hui-Wen']",Int J Mol Sci,,,True
5599f83a71c2303da5ac9a56d85ed29bab998507,PMC,Efficient production of glycyrrhetinic acid in metabolically engineered Saccharomyces cerevisiae via an integrated strategy,http://dx.doi.org/10.1186/s12934-019-1138-5,PMC6540369,31138208,CC BY,"BACKGROUND: Glycyrrhetinic acid (GA) is the most important ingredient in licorice due to its outstanding anti-inflammatory activity and wide application in the medicine and cosmetics industries. Contemporary industrial production of GA by acid hydrolysis of glycyrrhizin which was extracted from Glycyrrhiza plants, is not environment-friendly and devastates farmland since the Glycyrrhiza rhizomes grow up to 10 m underground. RESULTS: In this study, GA was produced through metabolically engineering Saccharomyces cerevisiae by introducing the entire heterogeneous biosynthetic pathway of GA. Codon optimized CYP88D6 and CYP72A154, combined with β-AS (β-amyrin synthase encoding gene) and the NADPH-cytochrome P450 reductase gene of Arabidopsis thaliana were introduced into S. cerevisiae. The resulting strain (Y1) produced 2.5 mg/L of β-amyrin and 14 μg/L of GA. The cytochrome b5 from G. uralensis (GuCYB5) was identified and the introduction of this novel GuCYB5 increased the efficiency of GA production by eightfold. The joint utilization of the GuCYB5 gene along with 10 known MVA pathway genes from S. cerevisiae were overexpressed in a stable chromosome integration to achieve higher GA production. Using the combined strategy, GA concentration improved by 40-fold during batch fermentation. The production was further improved to 8.78 mg/L in fed-batch fermentation, which was increased by a factor of nearly 630. CONCLUSIONS: This study first investigated the influence of carbon flux in the upstream module and the introduction of a newly identified GuCYB5 on GA production. The newly identified GuCYB5 was highly effective in improving GA production. An integrated strategy including enzyme discovery, pathway optimization, and fusion protein construction was provided in improving GA production, achieving a 630 fold increase in GA production. The metabolically engineered yeast cell factories provide an alternative approach to glycyrrhetinic acid production, replacing the traditional method of plant extraction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12934-019-1138-5) contains supplementary material, which is available to authorized users.",2019 May 28,"['Wang, Caixia', 'Su, Xinyao', 'Sun, Mengchu', 'Zhang, Mengting', 'Wu, Jiajia', 'Xing, Jianmin', 'Wang, Ying', 'Xue, Jianping', 'Liu, Xia', 'Sun, Wei', 'Chen, Shilin']",Microb Cell Fact,,,True
f8c2f1a1903f8370c15b5be2e4d32e91f2641b03,PMC,In vitro antiviral activity of fifteen plant extracts against avian infectious bronchitis virus,http://dx.doi.org/10.1186/s12917-019-1925-6,PMC6540435,31142304,CC BY,"BACKGROUND: Avian infectious bronchitis (IB) is a disease that can result in huge economic losses in the poultry industry. The high level of mutations of the IB virus (IBV) leads to the emergence of new serotypes and genotypes, and limits the efficacy of routine prevention. Medicinal plants, or substances derived from them, are being tested as options in the prevention of infectious diseases such as IB in many countries. The objective of this study was to investigate extracts of 15 selected medicinal plants for anti-IBV activity. RESULTS: Extracts of S. montana, O. vulgare, M. piperita, M. officinalis, T. vulgaris, H. officinalis, S. officinalis and D. canadense showed anti-IBV activity prior to and during infection, while S. montana showed activity prior to and after infection. M. piperita, O. vulgare and T. vulgaris extracts had > 60 SI. In further studies no virus plaques (plaque reduction rate 100%) or cytopathogenic effect (decrease of TCID(50) from 2.0 to 5.0 log(10)) were detected after IBV treatment with extracts of M. piperita, D. canadense and T. vulgaris at concentrations of extracts ≥0.25 cytotoxic concentration (CC(50)) (P < 0.05). Both PFU number and TCID(50) increased after the use of M. piperita, D. canadense, T. vulgaris and M. officinalis extracts, the concentrations of which were 0.125 CC(50) and 0.25 CC(50) (P < 0.05). Real-time PCR detected IBV RNA after treatment with all plant extracts using concentrations of 1:2 CC(50), 1:4 CC(50) and 1:8 CC(50). Delta cycle threshold (Ct) values decreased significantly comparing Ct values of 1:2 CC(50) and 1:8 CC(50) dilutions (P < 0.05). CONCLUSIONS: Many extracts of plants acted against IBV prior to and during infection, but the most effective were those of M. piperita, T. vulgaris and D. canadense .",2019 May 29,"['Lelešius, Raimundas', 'Karpovaitė, Agneta', 'Mickienė, Rūta', 'Drevinskas, Tomas', 'Tiso, Nicola', 'Ragažinskienė, Ona', 'Kubilienė, Loreta', 'Maruška, Audrius', 'Šalomskas, Algirdas']",BMC Vet Res,,,True
cc0396cb510d6413b537440d00ce0bf51abda136,PMC,Emodin Rescues Intrahepatic Cholestasis via Stimulating FXR/BSEP Pathway in Promoting the Canalicular Export of Accumulated Bile,http://dx.doi.org/10.3389/fphar.2019.00522,PMC6540617,31191298,CC BY,"AIM: Bile salt export pump (BSEP) have been confirmed to play an important role for bile acid canalicular export in the treatment of cholestasis. In this study, we investigated the stimulatory effect of emodin on BSEP signaling pathway in cholestasis. METHODS: Cell and animal experiments were given different concentrations of emodin. The BSEP upstream molecule farnesoid X receptor was down-regulated by small interfering RNA (siRNA) technology or guggulsterones and up-regulated by lentivirus or GW4064. Real-time PCR and Western blotting was employed to detect the mRNA and protein levels of BSEP in LO2 cell, rat primary hepatocytes and liver tissue. Immunohistochemistry (IHC) was used to examine the expression of BSEP in liver tissues. Rat liver function and pathological changes of liver tissue were performed by biochemical test and hematoxylin and eosin (HE) staining. RESULTS: Emodin could increase the mRNA and protein expression of BSEP and FXR. When down-regulating farnesoid X receptor expression with the siRNA or inhibitor guggulsterones, and up-regulating farnesoid X receptor expression with the lentivirus or agonist GW4064, emodin could increase the mRNA level of BSEP and FXR and the protein level of BSEP, FXR1, and FXR2. Emodin also had a notable effect on rat primary hepatocytes experiment, rat pathological manifestation, BSEP, FXR1, and FXR2 positive staining in liver tissues and the test of liver function. CONCLUSION: Emodin has a protective effect and a rescue activity on cholestasis via stimulating FXR/BSEP pathways in promoting the canalicular export of accumulated bile.",2019 May 22,"['Xiong, Xiao-Li', 'Ding, Yan', 'Chen, Zhi-Lin', 'Wang, Yao', 'Liu, Pan', 'Qin, Huan', 'Zhou, Li-Shan', 'Zhang, Ling-Ling', 'Huang, Juan', 'Zhao, Lei']",Front Pharmacol,,,True
39c58dbaa3f69e91698b2efe6d3b12504aa3904d,PMC,Neisseria gonorrhoeae uses cellular proteins CXCL10 and IL8 to enhance HIV‐1 transmission across cervical mucosa,http://dx.doi.org/10.1111/aji.13111,PMC6540971,30903720,CC BY,"PROBLEM: Neisseria gonorrhoeae (NG) infection has been shown to increase sexual transmission of HIV‐1. However, the mechanism of NG‐induced enhanced HIV‐1 transmission is unknown. METHODS: (a) The cervical tissues were exposed to NG, and cytokine induction was monitored by measuring cytokine proteins in culture supernatants and cytokine mRNAs in tissues. (b) Transcription and replication of HIV‐1 in TZM‐bl, U1, and ACH2 cells were measured by Beta‐Gal activity and p24 proteins in the supernatant, respectively. (c) HIV‐1 transmission was assayed in an organ culture system by measuring transmitted HIV‐1 in supernatant and HIV‐1 gag mRNA in the tissues. (d) Transcriptome analysis was done using second generation sequencing. RESULTS: (a) NG induced membrane ruffling of epithelial layer, caused migration of CD3+ cells to the intraepithelial region, and induced high levels of inflammatory cytokines IL‐1β and TNF‐α. (b) NG‐induced supernatants (NGIS) increased HIV‐1 transcription, induced HIV‐1 from latently infected cells, and increased transmission of HIV‐1 across cervical mucosa. (c) Transcriptome analysis of the epithelial layer of the tissues exposed to NG, and HIV‐1 showed significant upregulation of CXCL10 and IL8. IL‐1β increased the induction of CXCL10 and IL‐8 expression in cervical mucosa with a concomitant increase in HIV‐1 transmission. CONCLUSION: We present a model in which IL‐1β produced from cervical epithelium during NG exposure increases CXCL10 and IL8 in epithelia. This in turn causes upon HIV‐1 infection, the migration of HIV‐1 target cells toward the subepithelium, resulting in increased HIV‐1 transcription in the sub‐mucosa and subsequent enhancement of transmission across cervical mucosa.",2019 Jun 11,"['Sanyal, Anwesha', 'Shen, Chengli', 'Ding, Ming', 'Reinhart, Todd A.', 'Chen, Yue', 'Sankapal, Soni', 'Gupta, Phalguni']",Am J Reprod Immunol,,,True
9a2c1193b96d3e54da56f17d1060e236df5b0e38,PMC,Molecular and serological surveys of canine distemper virus: A meta-analysis of cross-sectional studies,http://dx.doi.org/10.1371/journal.pone.0217594,PMC6541297,31141576,CC BY,"BACKGROUND: Canine morbillivirus (canine distemper virus, CDV) persists as a serious threat to the health of domestic dogs and wildlife. Although studies have been conducted on the frequency and risk factors associated with CDV infection, there are no comprehensive data on the current epidemiological magnitude in the domestic dog population at regional and national levels. Therefore, we conducted a cross-sectional study and included our results in a meta-analysis to summarize and combine available data on the frequency and potential risk factors associated with CDV infection. METHODS: For the cross-sectional study, biological samples from dogs suspected to have canine distemper (CD) were collected and screened for viral RNA. Briefly, the PRISMA protocol was used for the meta-analysis, and data analyses were performed using STATA IC 13.1 software. RESULTS: CDV RNA was detected in 34% (48/141) of dogs suspected to have CD. Following our meta-analysis, 53 studies were selected for a total of 11,527 dogs. Overall, the pooled frequency of CDV positivity based on molecular and serological results were 33% (95% CI: 23–43) and 46% (95% CI: 36–57), respectively. The pooled subgroup analyses of clinical signs, types of biological samples, diagnostic methods and dog lifestyle had a wide range of CDV positivity (range 8–75%). Free-ranging dogs (OR: 1.44, 95% CI: 1.05–1.97), dogs >24 months old (OR: 1.83, 95% CI: 1.1–3) and unvaccinated dogs (OR: 2.92, 95% CI: 1.26–6.77) were found to be positively associated with CDV infection. In contrast, dogs <12 months old (OR: 0.36, 95% CI: 0.20–0.64) and dogs with a complete anti-CDV vaccination (OR: 0.18, 95% CI: 0.05–0.59) had a negative association. CONCLUSION: Considering the high frequency of CDV positivity associated with almost all the variables analyzed in dogs, it is necessary to immediately and continuously plan mitigation strategies to reduce the CDV prevalence, especially in determined endemic localities.",2019 May 29,"['da Costa, Vivaldo Gomes', 'Saivish, Marielena Vogel', 'Rodrigues, Roger Luiz', 'de Lima Silva, Rebeca Francielle', 'Moreli, Marcos Lázaro', 'Krüger, Ricardo Henrique']",PLoS One,,,True
e67d66fb0773322520aa527d533c6cffb08016a2,PMC,Lessening of porcine epidemic diarrhoea virus susceptibility in piglets after editing of the CMP-N-glycolylneuraminic acid hydroxylase gene with CRISPR/Cas9 to nullify N-glycolylneuraminic acid expression,http://dx.doi.org/10.1371/journal.pone.0217236,PMC6541307,31141512,CC BY,"The porcine epidemic diarrhoea virus (PEDV) devastates the health of piglets but may not infect piglets whose CMP-N-glycolylneuraminic acid hydroxylase (CMAH) gene is mutated (knockouts, KO) by using CRISPR/Cas9 gene editing techniques. This hypothesis was tested by using KO piglets that were challenged with PEDV. Two single-guide RNAs targeting the CMAH gene and Cas9 mRNA were microinjected into the cytoplasm of newly fertilized eggs. Four live founders generated and proven to be biallelic KO, lacking detectable N-glycolylneuraminic acid (NGNA). The founders were bred, and homozygous offspring were obtained. Two-day-old (in exps. I, n = 6, and III, n = 15) and 3-day-old (in exp. II, n = 9) KO and wild-type (WT, same ages in respective exps.) piglets were inoculated with TCID(50) 1x10(3) PEDV and then fed 20 mL of infant formula (in exps. I and II) or sow’s colostrum (in exp. III) every 4 hours. In exp. III, the colostrum was offered 6 times and was then replaced with Ringer/5% glucose solution. At 72 hours post-PEDV inoculation (hpi), the animals either deceased or euthanized were necropsied and intestines were sampled. In all 3 experiments, the piglets showed apparent outward clinical manifestations suggesting that infection occurred despite the CMAH KO. In exp. I, all 6 WT piglets and only 1 of 6 KO piglets died at 72 hpi. Histopathology and immunofluorescence staining showed that the villus epithelial cells of WT piglets were severely exfoliated, but only moderate exfoliation and enterocyte vacuolization was observed in KO piglets. In exp. II, delayed clinical symptoms appeared, yet the immunofluorescence staining/histopathologic inspection (I/H) scores of the two groups differed little. In exp. III, the animals exhibited clinical and pathological signs after inoculation similar to those in exp. II. These results suggest that porcine CMAH KO with nullified NGNA expression are not immune to PEDV but that this KO may lessen the severity of the infection and delay its occurrence.",2019 May 29,"['Tu, Ching-Fu', 'Chuang, Chin-kai', 'Hsiao, Kai-Hsuan', 'Chen, Chien-Hong', 'Chen, Chi-Min', 'Peng, Su-Hei', 'Su, Yu-Hsiu', 'Chiou, Ming-Tang', 'Yen, Chon-Ho', 'Hung, Shao-Wen', 'Yang, Tien-Shuh', 'Chen, Chuan-Mu']",PLoS One,,,True
879b563cbe739c7ec914ce9eef39d9a85d6d3801,PMC,Sepsis and septic shock: endothelial molecular pathogenesis associated with vascular microthrombotic disease,http://dx.doi.org/10.1186/s12959-019-0198-4,PMC6542012,31160889,CC BY,"In addition to protective “immune response”, sepsis is characterized by destructive “endothelial response” of the host, leading to endotheliopathy and its molecular dysfunction. Complement activation generates membrane attack complex (MAC). MAC causes channel formation to the cell membrane of pathogen, leading to death of microorganisms. In the host, MAC also may induce channel formation to innocent bystander endothelial cells (ECs) and ECs cannot be protected. This provokes endotheliopathy, which activates two independent molecular pathways: inflammatory and microthrombotic. Activated inflammatory pathway promotes the release of inflammatory cytokines and triggers inflammation. Activated microthrombotic pathway mediates platelet activation and exocytosis of unusually large von Willebrand factor multimers (ULVWF) from ECs and initiates microthrombogenesis. Excessively released ULVWF become anchored to ECs as long elongated strings and recruit activated platelets to assemble platelet-ULVWF complexes and form “microthrombi”. These microthrombi strings trigger disseminated intravascular microthrombosis (DIT), which is the underlying pathology of endotheliopathy-associated vascular microthrombotic disease (EA-VMTD). Sepsis-induced endotheliopathy promotes inflammation and DIT. Inflammation produces inflammatory response and DIT orchestrates consumptive thrombocytopenia, microangiopathic hemolytic anemia, and multiorgan dysfunction syndrome (MODS). Systemic inflammatory response syndrome (SIRS) is a combined phenotype of inflammation and endotheliopathy-associated (EA)-VMTD. Successful therapeutic design for sepsis can be achieved by counteracting the pathologic microthrombogenesis.",2019 May 30,"Chang, Jae C.",Thromb J,,,True
a977f44a0323a1017c2ba7e0ba03432fbf9aa822,PMC,What can urban mobility data reveal about the spatial distribution of infection in a single city?,http://dx.doi.org/10.1186/s12889-019-6968-x,PMC6542035,31142311,CC BY,"BACKGROUND: Infectious diseases spread through inherently spatial processes. Road and air traffic data have been used to model these processes at national and global scales. At metropolitan scales, however, mobility patterns are fundamentally different and less directly observable. Estimating the spatial distribution of infection has public health utility, but few studies have investigated this at an urban scale. In this study we address the question of whether the use of urban-scale mobility data can improve the prediction of spatial patterns of influenza infection. We compare the use of different sources of urban-scale mobility data, and investigate the impact of other factors relevant to modelling mobility, including mixing within and between regions, and the influence of hub and spoke commuting patterns. METHODS: We used journey-to-work (JTW) data from the Australian 2011 Census, and GPS journey data from the Sygic GPS Navigation & Maps mobile app, to characterise population mixing patterns in a spatially-explicit SEIR (susceptible, exposed, infectious, recovered) meta-population model. RESULTS: Using the JTW data to train the model leads to an increase in the proportion of infections that arise in central Melbourne, which is indicative of the city’s spoke-and-hub road and public transport networks, and of the commuting patterns reflected in these data. Using the GPS data increased the infections in central Melbourne to a lesser extent than the JTW data, and produced a greater heterogeneity in the middle and outer regions. Despite the limitations of both mobility data sets, the model reproduced some of the characteristics observed in the spatial distribution of reported influenza cases. CONCLUSIONS: Urban mobility data sets can be used to support models that capture spatial heterogeneity in the transmission of infectious diseases at a metropolitan scale. These data should be adjusted to account for relevant urban features, such as highly-connected hubs where the resident population is likely to experience a much lower force of infection that the transient population. In contrast to national and international scales, the relationship between mobility and infection at an urban level is much less apparent, and requires a richer characterisation of population mobility and contact. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-019-6968-x) contains supplementary material, which is available to authorized users.",2019 May 29,"['Moss, Robert', 'Naghizade, Elham', 'Tomko, Martin', 'Geard, Nicholas']",BMC Public Health,,,True
955b36f4b007abbfaa28385a627b03e2102313d9,PMC,What can urban mobility data reveal about the spatial distribution of infection in a single city?,http://dx.doi.org/10.1186/s12889-019-6968-x,PMC6542035,31142311,CC BY,"BACKGROUND: Infectious diseases spread through inherently spatial processes. Road and air traffic data have been used to model these processes at national and global scales. At metropolitan scales, however, mobility patterns are fundamentally different and less directly observable. Estimating the spatial distribution of infection has public health utility, but few studies have investigated this at an urban scale. In this study we address the question of whether the use of urban-scale mobility data can improve the prediction of spatial patterns of influenza infection. We compare the use of different sources of urban-scale mobility data, and investigate the impact of other factors relevant to modelling mobility, including mixing within and between regions, and the influence of hub and spoke commuting patterns. METHODS: We used journey-to-work (JTW) data from the Australian 2011 Census, and GPS journey data from the Sygic GPS Navigation & Maps mobile app, to characterise population mixing patterns in a spatially-explicit SEIR (susceptible, exposed, infectious, recovered) meta-population model. RESULTS: Using the JTW data to train the model leads to an increase in the proportion of infections that arise in central Melbourne, which is indicative of the city’s spoke-and-hub road and public transport networks, and of the commuting patterns reflected in these data. Using the GPS data increased the infections in central Melbourne to a lesser extent than the JTW data, and produced a greater heterogeneity in the middle and outer regions. Despite the limitations of both mobility data sets, the model reproduced some of the characteristics observed in the spatial distribution of reported influenza cases. CONCLUSIONS: Urban mobility data sets can be used to support models that capture spatial heterogeneity in the transmission of infectious diseases at a metropolitan scale. These data should be adjusted to account for relevant urban features, such as highly-connected hubs where the resident population is likely to experience a much lower force of infection that the transient population. In contrast to national and international scales, the relationship between mobility and infection at an urban level is much less apparent, and requires a richer characterisation of population mobility and contact. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-019-6968-x) contains supplementary material, which is available to authorized users.",2019 May 29,"['Moss, Robert', 'Naghizade, Elham', 'Tomko, Martin', 'Geard, Nicholas']",BMC Public Health,,,True
70b27df77b5f3ef4c9be9028cc34110d4dd7d22b,PMC,Serological evidence and experimental infection of cynomolgus macaques with pteropine orthoreovirus reveal monkeys as potential hosts for transmission to humans,http://dx.doi.org/10.1080/22221751.2019.1621668,PMC6542153,31132935,CC BY,"Pteropine orthoreoviruses (PRV) are emerging bat-borne viruses with proven zoonotic transmission. We recently demonstrated human exposure to PRV in Singapore, which together with previous reports from Malaysia and Vietnam suggest that human infection of PRV may occur periodically in the region. This raises the question whether bats are the only sources of human infection. In this study, we screened 517 cynomolgus macaques caught in Singapore for evidence of exposure to PRV3M (also known as Melaka virus), which was first isolated from human patients in Melaka, Malaysia. We found that 67 serum samples were PRV3M positive by ELISA and 34 were also positive by virus neutralization assay. To investigate whether monkeys could act as hosts for PRV transmission, we experimentally infected cynomolgus macaques with PRV3M and housed these animals with uninfected monkeys. Although no clinical signs of infection were observed in infected animals, viral RNA was detected in nasal and rectal swabs and all infected macaques seroconverted. Additionally, one of the uninfected animals seroconverted, implying active shedding and transmission of PRV3M. We provide evidence that PRV exposure in the macaque population in Singapore occurs at a relatively high prevalence and this study suggests that cynomolgus macaques may be an intermediate or reservoir host for PRVs.",2019 May 28,"['Tan, Chee Wah', 'Wittwer, Kevin', 'Lim, Xiao Fang', 'Uehara, Anna', 'Mani, Shailendra', 'Wang, Lin-Fa', 'Anderson, Danielle E.']",Emerg Microbes Infect,,,True
8377296478e62e2cd582fed23e9e20f512d5e92d,PMC,Convalescent patient-derived monoclonal antibodies targeting different epitopes of E protein confer protection against Zika virus in a neonatal mouse model,http://dx.doi.org/10.1080/22221751.2019.1614885,PMC6542155,31130109,CC BY,"The Zika virus (ZIKV) outbreak and its link to microcephaly triggered a public health concern. To examine antibody response in a patient infected with ZIKV, we used single-cell PCR to clone 31 heavy and light chain-paired monoclonal antibodies (mAbs) that bind to ZIKV envelope (E) proteins isolated from memory B cells of a ZIKV-infected patient. Three mAbs (7B3, 1C11, and 6A6) that showed the most potent and broad neutralization activities against the African, Asian, and American strains were selected for further analysis. mAb 7B3 showed an IC50 value of 11.6 ng/mL against the circulating American strain GZ02. Epitope mapping revealed that mAbs 7B3 and 1C11 targeted residue K394 of the lateral ridge (LR) epitope of the EDIII domain, but 7B3 has a broader LR epitope footprint and recognizes residues T335, G337, E370, and N371 as well. mAb 6A6 recognized residues D67, K118, and K251 of the EDII domain. Interestingly, although the patient was seronegative for DENV infection, mAb 1C11, originating from the VH3-23 and VK1-5 germline pair, neutralized both ZIKV and DENV1. Administration of the mAbs 7B3, 1C11, and 6A6 protected neonatal SCID mice infected with a lethal dose of ZIKV. This study provides potential therapeutic antibody candidates and insights into the antibody response after ZIKV infection.",2019 May 25,"['Niu, Xuefeng', 'Zhao, Lingzhai', 'Qu, Linbing', 'Yao, Zhipeng', 'Zhang, Fan', 'Yan, Qihong', 'Zhang, Shengnan', 'Liang, Renshan', 'Chen, Peihai', 'Luo, Jia', 'Xu, Wei', 'Lv, Huibin', 'Liu, Xinglong', 'Lei, Hui', 'Yi, Changhua', 'Li, Pingchao', 'Wang, Qian', 'Wang, Yang', 'Yu, Lei', 'Zhang, Xiaoyan', 'Bryan, L. Aubrey', 'Davidson, Edgar', 'Doranz, j. Benjamin', 'Feng, Liqiang', 'Pan, Weiqi', 'Zhang, Fuchun', 'Chen, Ling']",Emerg Microbes Infect,,,True
89c52fc69362dbc2c29ed79aa72928ad14dc4c80,PMC,Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection,http://dx.doi.org/10.1080/22221751.2019.1620083,PMC6542157,31130102,CC BY,"The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.",2019 May 25,"['Jia, Wenxu', 'Channappanavar, Rudragouda', 'Zhang, Chao', 'Li, Mingxi', 'Zhou, Haixia', 'Zhang, Shuyuan', 'Zhou, Panpan', 'Xu, Jiuyang', 'Shan, Sisi', 'Shi, Xuanling', 'Wang, Xinquan', 'Zhao, Jincun', 'Zhou, Dongming', 'Perlman, Stanley', 'Zhang, Linqi']",Emerg Microbes Infect,,,True
47dbf69e1dd55cac224b406467542111d2124c06,PMC,Trends in the travelers’ demand for pre-travel medical advice at a Spanish International Vaccination Center between 2000 and 2017,http://dx.doi.org/10.1371/journal.pone.0217588,PMC6542509,31145759,CC BY,"Crises and disasters affect the numbers of people traveling either for tourism or other reasons. Many studies have been published on the effects of such events on travel, especially on tourism, and based on the arrivals or departures of travelers to or from countries. Our aim was to assess the influence of these events on the demand for pre-travel medical consultation in an International Vaccination Centre (IVC). Data on 94683 international travelers who visited 113529 international destinations attended at the IVC of Malaga (Spain) during 2000–2017 were studied. A descriptive and time series analyses was conducted. The demand to IVC was 3.47 times higher in 2017 than in 2000. The increase has not been the same for all destinations: Travel to South-East Asia and Western Pacific World Health Organization (WHO) regions has multiplied by 10, while in the same period, Africa WHO region has declined from 36% to 20% of total demand. Thailand, India and Brazil were the countries with the highest demand (21% of all pre-travel consultations). We found out three periods, concurrent with some socioeconomic or health events, in which the number of travellers attend decline with respect to the previous years, or the growth was very slow. Growth in the demand for pre-travel medical advice in parallel with a foreseeable increase in the number of travelers is expected. Pre-travel medical services must be adapted to this increase. This study of the trend of demand for pre-travel medical information should new related problems to travel to be identified and quantified, and should assist improvement of policies and programs aimed at care of travelers.",2019 May 30,"['Segura, Marina', 'Lopez-Gigosos, Rosa', 'Mariscal-Lopez, Eloisa', 'Gutierrez-Bedmar, Mario', 'Mariscal, Alberto']",PLoS One,,,True
e58bb3ad5e35a2895353e82c3690e2dd33a8d86b,PMC,SPI-1 is a missing host-range factor required for replication of the attenuated modified vaccinia Ankara (MVA) vaccine vector in human cells,http://dx.doi.org/10.1371/journal.ppat.1007710,PMC6542542,31145755,CC0,"Modified vaccinia virus Ankara (MVA) is the leading poxvirus vector for development of vaccines against diverse infectious diseases. This distinction is based on high expression of proteins and good immunogenicity despite an inability to assemble infectious progeny in human cells, which together promote efficacy and safety. Nevertheless, the basis for the host-range restriction is unknown despite past systematic attempts to identify the relevant missing viral gene(s). The search for host-range factors is exacerbated by the large number of deletions, truncations and mutations that occurred during the long passage history of MVA in chicken embryo fibroblasts. By whole genome sequencing of a panel of recombinant host-range extended (HRE) MVAs generated by marker rescue with 40 kbp segments of vaccinia virus DNA, we identified serine protease inhibitor 1 (SPI-1) as one of several candidate host-range factors present in those viruses that gained the ability to replicate in human cells. Electron microscopy revealed that the interruption of morphogenesis in human cells infected with MVA occurred at a similar stage as that of a vaccinia virus strain WR SPI-1 deletion mutant. Moreover, the introduction of the SPI-1 gene into the MVA genome led to more than a 2-log enhancement of virus spread in human diploid MRC-5 cells, whereas deletion of the gene diminished the spread of HRE viruses by similar extents. Furthermore, MRC-5 cells stably expressing SPI-1 also enhanced replication of MVA. A role for additional host range genes was suggested by the restoration of MVA replication to a lower level relative to HRE viruses, particularly in other human cell lines. Although multiple sequence alignments revealed genetic changes in addition to SPI-1 common to the HRE MVAs, no evidence for their host-range function was found by analysis thus far. Our finding that SPI-1 is host range factor for MVA should simplify use of high throughput RNAi or CRISPR/Cas single gene methods to identify additional viral and human restriction elements.",2019 May 30,"['Liu, Ruikang', 'Mendez-Rios, Jorge D.', 'Peng, Chen', 'Xiao, Wei', 'Weisberg, Andrea S.', 'Wyatt, Linda S.', 'Moss, Bernard']",PLoS Pathog,,,True
51b006f1087fca529dbda94f2ab41c71acc09654,PMC,"Editorial: Concepts and Experiences in Framing, Integration and Evaluation of One Health and EcoHealth",http://dx.doi.org/10.3389/fvets.2019.00155,PMC6544039,31214602,CC BY,,2019 May 24,"['Rüegg, Simon R.', 'Buttigieg, Sandra C.', 'Goutard, Flavie L.', 'Binot, Aurélie', 'Morand, Serge', 'Thys, Séverine', 'Keune, Hans']",Front Vet Sci,,,True
d6b9d859c6892fcfcd101ef2e23b62531614b31c,PMC,A dual controllability analysis of influenza virus-host protein-protein interaction networks for antiviral drug target discovery,http://dx.doi.org/10.1186/s12859-019-2917-z,PMC6545738,31159726,CC BY,"BACKGROUND: Host factors of influenza virus replication are often found in key topological positions within protein-protein interaction networks. This work explores how protein states can be manipulated through controllability analysis: the determination of the minimum manipulation needed to drive the cell system to any desired state. Here, we complete a two-part controllability analysis of two protein networks: a host network representing the healthy cell state and an influenza A virus-host network representing the infected cell state. In this context, controllability analyses aim to identify key regulating host factors of the infected cell’s progression. This knowledge can be utilized in further biological analysis to understand disease dynamics and isolate proteins for study as drug target candidates. RESULTS: Both topological and controllability analyses provide evidence of wide-reaching network effects stemming from the addition of viral-host protein interactions. Virus interacting and driver host proteins are significant both topologically and in controllability, therefore playing important roles in cell behavior during infection. Functional analysis finds overlap of results with previous siRNA studies of host factors involved in influenza replication, NF-kB pathway and infection relevance, and roles as interferon regulating genes. 24 proteins are identified as holding regulatory roles specific to the infected cell by measures of topology, controllability, and functional role. These proteins are recommended for further study as potential antiviral drug targets. CONCLUSIONS: Seasonal outbreaks of influenza A virus are a major cause of illness and death around the world each year with a constant threat of pandemic infection. This research aims to increase the efficiency of antiviral drug target discovery using existing protein-protein interaction data and network analysis methods. These results are beneficial to future studies of influenza virus, both experimental and computational, and provide evidence that the combination of topology and controllability analyses may be valuable for future efforts in drug target discovery. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-019-2917-z) contains supplementary material, which is available to authorized users.",2019 Jun 3,"['Ackerman, Emily E.', 'Alcorn, John F.', 'Hase, Takeshi', 'Shoemaker, Jason E.']",BMC Bioinformatics,,,False
ca5775b18f2a5c86fc3efd929ef997a189fd1705,PMC,A dual controllability analysis of influenza virus-host protein-protein interaction networks for antiviral drug target discovery,http://dx.doi.org/10.1186/s12859-019-2917-z,PMC6545738,31159726,CC BY,"BACKGROUND: Host factors of influenza virus replication are often found in key topological positions within protein-protein interaction networks. This work explores how protein states can be manipulated through controllability analysis: the determination of the minimum manipulation needed to drive the cell system to any desired state. Here, we complete a two-part controllability analysis of two protein networks: a host network representing the healthy cell state and an influenza A virus-host network representing the infected cell state. In this context, controllability analyses aim to identify key regulating host factors of the infected cell’s progression. This knowledge can be utilized in further biological analysis to understand disease dynamics and isolate proteins for study as drug target candidates. RESULTS: Both topological and controllability analyses provide evidence of wide-reaching network effects stemming from the addition of viral-host protein interactions. Virus interacting and driver host proteins are significant both topologically and in controllability, therefore playing important roles in cell behavior during infection. Functional analysis finds overlap of results with previous siRNA studies of host factors involved in influenza replication, NF-kB pathway and infection relevance, and roles as interferon regulating genes. 24 proteins are identified as holding regulatory roles specific to the infected cell by measures of topology, controllability, and functional role. These proteins are recommended for further study as potential antiviral drug targets. CONCLUSIONS: Seasonal outbreaks of influenza A virus are a major cause of illness and death around the world each year with a constant threat of pandemic infection. This research aims to increase the efficiency of antiviral drug target discovery using existing protein-protein interaction data and network analysis methods. These results are beneficial to future studies of influenza virus, both experimental and computational, and provide evidence that the combination of topology and controllability analyses may be valuable for future efforts in drug target discovery. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-019-2917-z) contains supplementary material, which is available to authorized users.",2019 Jun 3,"['Ackerman, Emily E.', 'Alcorn, John F.', 'Hase, Takeshi', 'Shoemaker, Jason E.']",BMC Bioinformatics,,,True
2a5f81ece752816e85edfe177f324c522228f292,PMC,Human coronavirus alone or in co-infection with rhinovirus C is a risk factor for severe respiratory disease and admission to the pediatric intensive care unit: A one-year study in Southeast Brazil,http://dx.doi.org/10.1371/journal.pone.0217744,PMC6546210,31158256,CC BY,"OBJECTIVE: We aimed to assess the profile of respiratory viruses in young children hospitalized for acute lower respiratory tract infection (ALRI) and its association with disease severity, defined as need for pediatric intensive care unit (PICU) admission. DESIGN: Prospective observational cohort study. SETTING: A tertiary-care university hospital in Brazil. PATIENTS: Children younger than three years attending the pediatric emergency room with ALRI who were admitted to the hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nasopharyngeal aspirates were collected from patients from June 1(st), 2008 to May 31(st), 2009within the first 48 hours of hospitalization. Nasopharyngeal aspirates were tested for 17humanrespiratory viruses by molecular and immunofluorescence based assays. Simple and multiple log-binomial regression models were constructed to assess associations of virus type with a need for PICU admission. Age, prematurity, the presence of an underlying disease and congenital heart disease were covariates. Nasopharyngeal aspirates were positive for at least one virus in 236 patients. Rhinoviruses were detected in 85.6% of samples, with a preponderance of rhinovirus C (RV-C) (61.9%). Respiratory syncytial virus was detected in 59.8% and human coronavirus (HCoV) in 11% of the samples. Co-detections of two to five viruses were found in 78% of the patients. The detection of HCoV alone (adjusted relative risk (RR) 2.18; 95% CI 1.15–4.15) or in co-infection with RV-C (adjusted RR 2.37; 95% CI 1.23–4.58) was independently associated with PICU admission. CONCLUSIONS: The detection of HCoV alone or in co-infection with RV-C was independently associated with PICU admission in young children hospitalized for ALRI.",2019 Jun 3,"['Matsuno, Alessandra K.', 'Gagliardi, Talita B.', 'Paula, Flavia E.', 'Luna, Luciano K. S.', 'Jesus, Bruna L. S.', 'Stein, Renato T.', 'Aragon, Davi C.', 'Carlotti, Ana P. C. P.', 'Arruda, Eurico']",PLoS One,,,True
cd50536bcd80b20330a1382bbcb0f895748e338a,PMC,Porcine parvovirus VP1/VP2 on a time series epitope mapping: exploring the effects of high hydrostatic pressure on the immune recognition of antigens,http://dx.doi.org/10.1186/s12985-019-1165-1,PMC6547530,31159841,CC BY,"Porcine parvovirus (PPV) is a DNA virus that causes reproductive failure in gilts and sows, resulting in embryonic and fetal losses worldwide. Epitope mapping of PPV is important for developing new vaccines. In this study, we used spot synthesis analysis for epitope mapping of the capsid proteins of PPV (NADL-2 strain) and correlated the findings with predictive data from immunoinformatics. The virus was exposed to three conditions prior to inoculation in pigs: native (untreated), high hydrostatic pressure (350 MPa for 1 h) at room temperature and high hydrostatic pressure (350 MPa for 1 h) at − 18 °C, and was compared with a commercial vaccine produced using inactivated PPV. The screening of serum samples detected 44 positive spots corresponding to 20 antigenic sites. Each type of inoculated antigen elicited a distinct epitope set. In silico prediction located linear and discontinuous epitopes in B cells that coincided with several epitopes detected in spot synthesis of sera from pigs that received different preparations of inoculum. The conditions tested elicited antibodies against the VP1/VP2 antigen that differed in relation to the response time and the profile of structurally available regions that were recognized. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-019-1165-1) contains supplementary material, which is available to authorized users.",2019 Jun 3,"['de Souza, Ancelmo Rabelo', 'Yamin, Marriam', 'Gava, Danielle', 'Zanella, Janice Reis Ciacci', 'Gatti, Maria Sílvia Viccari', 'Bonafe, Carlos Francisco Sampaio', 'de Lima Neto, Daniel Ferreira']",Virol J,,,True
3319b5fd5749bba0f2fa25f335cc8c19b351a403,PMC,SARS-Coronavirus Open Reading Frame-8b triggers intracellular stress pathways and activates NLRP3 inflammasomes,http://dx.doi.org/10.1038/s41420-019-0181-7,PMC6549181,31231549,CC BY,"The SARS (severe acute respiratory syndrome) outbreak was caused by a coronavirus (CoV) named the SARS-CoV. SARS pathology is propagated both by direct cytotoxic effects of the virus and aberrant activation of the innate immune response. Here, we identify several mechanisms by which a SARS-CoV open reading frame (ORF) activates intracellular stress pathways and targets the innate immune response. We show that ORF8b forms insoluble intracellular aggregates dependent on a valine at residue 77. Aggregated ORF8b induces endoplasmic reticulum (ER) stress, lysosomal damage, and subsequent activation of the master regulator of the autophagy and lysosome machinery, Transcription factor EB (TFEB). ORF8b causes cell death in epithelial cells, which is partially rescued by reducing its ability to aggregate. In macrophages, ORF8b robustly activates the NLRP3 inflammasome by providing a potent signal 2 required for activation. Mechanistically, ORF8b interacts directly with the Leucine Rich Repeat domain of NLRP3 and localizes with NLRP3 and ASC in cytosolic dot-like structures. ORF8b triggers cell death consistent with pyroptotic cell death in macrophages. While in those cells lacking NLRP3 accumulating ORF8b cytosolic aggregates cause ER stress, mitochondrial dysfunction, and caspase-independent cell death.",2019 Jun 5,"['Shi, Chong-Shan', 'Nabar, Neel R.', 'Huang, Ning-Na', 'Kehrl, John H.']",Cell Death Discov,,,True
efcfbaace6df1f5383c167fe24ecfd918b77f8b4,PMC,TAR-VIR: a pipeline for TARgeted VIRal strain reconstruction from metagenomic data,http://dx.doi.org/10.1186/s12859-019-2878-2,PMC6549370,31164077,CC BY,"BACKGROUND: Strain-level RNA virus characterization is essential for developing prevention and treatment strategies. Viral metagenomic data, which can contain sequences of both known and novel viruses, provide new opportunities for characterizing RNA viruses. Although there are a number of pipelines for analyzing viruses in metagenomic data, they have different limitations. First, viruses that lack closely related reference genomes cannot be detected with high sensitivity. Second, strain-level analysis is usually missing. RESULTS: In this study, we developed a hybrid pipeline named TAR-VIR that reconstructs viral strains without relying on complete or high-quality reference genomes. It is optimized for identifying RNA viruses from metagenomic data by combining an effective read classification method and our in-house strain-level de novo assembly tool. TAR-VIR was tested on both simulated and real viral metagenomic data sets. The results demonstrated that TAR-VIR competes favorably with other tested tools. CONCLUSION: TAR-VIR can be used standalone for viral strain reconstruction from metagenomic data. Or, its read recruiting stage can be used with other de novo assembly tools for superior viral functional and taxonomic analyses. The source code and the documentation of TAR-VIR are available at https://github.com/chjiao/TAR-VIR. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-019-2878-2) contains supplementary material, which is available to authorized users.",2019 Jun 4,"['Chen, Jiao', 'Huang, Jiating', 'Sun, Yanni']",BMC Bioinformatics,,,True
2debc2b3a63c04c798cb30f704911b63d44ec841,PMC,TAR-VIR: a pipeline for TARgeted VIRal strain reconstruction from metagenomic data,http://dx.doi.org/10.1186/s12859-019-2878-2,PMC6549370,31164077,CC BY,"BACKGROUND: Strain-level RNA virus characterization is essential for developing prevention and treatment strategies. Viral metagenomic data, which can contain sequences of both known and novel viruses, provide new opportunities for characterizing RNA viruses. Although there are a number of pipelines for analyzing viruses in metagenomic data, they have different limitations. First, viruses that lack closely related reference genomes cannot be detected with high sensitivity. Second, strain-level analysis is usually missing. RESULTS: In this study, we developed a hybrid pipeline named TAR-VIR that reconstructs viral strains without relying on complete or high-quality reference genomes. It is optimized for identifying RNA viruses from metagenomic data by combining an effective read classification method and our in-house strain-level de novo assembly tool. TAR-VIR was tested on both simulated and real viral metagenomic data sets. The results demonstrated that TAR-VIR competes favorably with other tested tools. CONCLUSION: TAR-VIR can be used standalone for viral strain reconstruction from metagenomic data. Or, its read recruiting stage can be used with other de novo assembly tools for superior viral functional and taxonomic analyses. The source code and the documentation of TAR-VIR are available at https://github.com/chjiao/TAR-VIR. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-019-2878-2) contains supplementary material, which is available to authorized users.",2019 Jun 4,"['Chen, Jiao', 'Huang, Jiating', 'Sun, Yanni']",BMC Bioinformatics,,,True
1894cac8794748c11482c059bc5a2c6d4f1e9527,PMC,Spectrum of Viral Infections Among Primary Immunodeficient Children: Report From a National Registry,http://dx.doi.org/10.3389/fimmu.2019.01231,PMC6549382,31191561,CC BY,"Objective: To present the frequency and spectrum of viral infections in primary immunodeficient children. Methods: The data was obtained from the Kuwait National Primary Immunodeficiency Disorders (PIDs) Registry during the period of 2004-2018. Results: A total of 274 PID children were registered in KNPIDR during the study period with predominance of immunodeficiencies affecting cellular and humoral immunity, followed by combined immunodeficiencies with associated syndromic features and diseases of immune dysregulation. Overall infectious complications affected 82.4% of the patients, and viral infections affected 31.7% of the registered patients. Forty-five patients (16.4%) developed viral infections caused by at least 2 organisms, among those 20 patients were affected by three or more viral infections. There was a statistically significant association between viral infections and PID category. However, there was no statistically significant association between viral infections and gender or the patients' onset age. There was a total of 170 viral infections during the study period and the causes of these infections were predominated by CMV (22.2%), adenovirus (11.7%), EBV (11.1%), and enteroviruses (7.4%). CMV and parainfluenza infections were more common in the group of immunodeficiencies affecting cellular and humoral immunity while EBV and human papilloma virus (HPV) were more common in the immune dysregulation group and combined immunodeficiencies with associated syndromic features, respectively. The most common presentation was viremia (28.8%) followed by pneumonia (28.2%) and skin infections (17.6%). The most common causes of viremia were CMV followed by adenovirus and EBV, while the most common organisms causing pneumonia were CMV followed by rhinovirus and parainfluenza. There were 80 deaths among the registered patients, 10% were caused by viral infections. Conclusions: Viral infections are common in PIDs and result into a wide-range of clinical manifestations causing significant morbidity and mortality.",2019 May 29,"['Al-Herz, Waleed', 'Essa, Sahar']",Front Immunol,,,True
236bd666a76213bc131969e1d5b66e410fc1cd45,PMC,"Acute Phase Proteins in Marine Mammals: State of Art, Perspectives and Challenges",http://dx.doi.org/10.3389/fimmu.2019.01220,PMC6549532,31191557,CC BY,"The term “acute phase response” (APR) is referred to a nonspecific and complex reaction of an organism that occurs shortly after any tissue damage, such as infection, trauma, neoplasia, inflammation, and stress. The APR can be identified and monitored with some laboratory tests, such as the concentration of several plasma proteins, the acute phase proteins (APPs). The APPs are components of the non-specific innate immune response, and their plasma concentration is proportional to the severity and/or the extent of tissue damage. The evaluation of health status of marine mammals is difficult because the classical clinical signs of illness used for human and domestic animals are difficult to recognize and understand. For this reason, in the past years, several efforts were done to identify laboratory markers of disease in these animals. The APPs have demonstrated their role as early markers of inflammation in veterinary medicine, thus several APPs were tested in marine mammals, such as C-reactive protein (CRP), serum amyloid-A (SAA), and Haptoglobin (Hp). However, the difficulty to extrapolate the knowledge about APPs in one species to another, the lack of specie-specific reagents, the absence of data about negative APPs have hampered their extent use in marine mammals. Herein, the state of art of APPs in marine mammals is reviewed, with particular attention to pre-analytical and analytical factors that should be taken into account in validation and interpretation of APPs assays. Moreover, the current application, potential utility and the future developments of APPs in marine mammals is highlighted and discussed.",2019 May 29,"['Gelain, Maria Elena', 'Bonsembiante, Federico']",Front Immunol,,,True
14374db205f6934d9cba148624462000bc6ec7be,PMC,Antibody Treatment against Angiopoietin-Like 4 Reduces Pulmonary Edema and Injury in Secondary Pneumococcal Pneumonia,http://dx.doi.org/10.1128/mBio.02469-18,PMC6550533,31164474,CC BY,"Secondary bacterial lung infection by Streptococcus pneumoniae (S. pneumoniae) poses a serious health concern, especially in developing countries. We posit that the emergence of multiantibiotic-resistant strains will jeopardize current treatments in these regions. Deaths arising from secondary infections are more often associated with acute lung injury, a common consequence of hypercytokinemia, than with the infection per se. Given that secondary bacterial pneumonia often has a poor prognosis, newer approaches to improve treatment outcomes are urgently needed to reduce the high levels of morbidity and mortality. Using a sequential dual-infection mouse model of secondary bacterial lung infection, we show that host-directed therapy via immunoneutralization of the angiopoietin-like 4 c-isoform (cANGPTL4) reduced pulmonary edema and damage in infected mice. RNA sequencing analysis revealed that anti-cANGPTL4 treatment improved immune and coagulation functions and reduced internal bleeding and edema. Importantly, anti-cANGPTL4 antibody, when used concurrently with either conventional antibiotics or antipneumolysin antibody, prolonged the median survival of mice compared to monotherapy. Anti-cANGPTL4 treatment enhanced immune cell phagocytosis of bacteria while restricting excessive inflammation. This modification of immune responses improved the disease outcomes of secondary pneumococcal pneumonia. Taken together, our study emphasizes that host-directed therapeutic strategies are viable adjuncts to standard antimicrobial treatments.",2019 Jun 4,"['Li, Liang', 'Foo, Benjamin Jie Wei', 'Kwok, Ka Wai', 'Sakamoto, Noriho', 'Mukae, Hiroshi', 'Izumikawa, Koichi', 'Mandard, Stéphane', 'Quenot, Jean-Pierre', 'Lagrost, Laurent', 'Teh, Wooi Keong', 'Singh Kohli, Gurjeet', 'Zhu, Pengcheng', 'Choi, Hyungwon', 'Buist, Martin Lindsay', 'Seet, Ju Ee', 'Yang, Liang', 'He, Fang', 'Kwong Chow, Vincent Tak', 'Tan, Nguan Soon']",mBio,,,True
af678e8cd31d74cdb2d690addc19d59dca331f2b,PMC,Quantifying the seasonal drivers of transmission for Lassa fever in Nigeria,http://dx.doi.org/10.1098/rstb.2018.0268,PMC6553602,31056054,CC BY,"Lassa fever (LF) is a zoonotic disease that is widespread in West Africa and involves animal-to-human and human-to-human transmission. Animal-to-human transmission occurs upon exposure to rodent excreta and secretions, i.e. urine and saliva, and human-to-human transmission occurs via the bodily fluids of an infected person. To elucidate the seasonal drivers of LF epidemics, we employed a mathematical model to analyse the datasets of human infection, rodent population dynamics and climatological variations and capture the underlying transmission dynamics. The surveillance-based incidence data of human cases in Nigeria were explored, and moreover, a mathematical model was used for describing the transmission dynamics of LF in rodent populations. While quantifying the case fatality risk and the rate of exposure of humans to animals, we explicitly estimated the corresponding contact rate of humans with infected rodents, accounting for the seasonal population dynamics of rodents. Our findings reveal that seasonal migratory dynamics of rodents play a key role in regulating the cyclical pattern of LF epidemics. The estimated timing of high exposure of humans to animals coincides with the time shortly after the start of the dry season and can be associated with the breeding season of rodents in Nigeria. This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’. This issue is linked with the subsequent theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’.",2019 Jun 24,"['Akhmetzhanov, Andrei R.', 'Asai, Yusuke', 'Nishiura, Hiroshi']",Philos Trans R Soc Lond B Biol Sci,,,True
42b049c2b5b32c094dc8b10f967e43ac2169b890,PMC,"Evaluation of the influenza-like illness surveillance system in Tunisia, 2012–2015",http://dx.doi.org/10.1186/s12889-019-7035-3,PMC6555026,31170955,CC BY,"BACKGROUND: This study was initiated to evaluate, for the first time, the performance and quality of the influenza-like illness (ILI) surveillance system in Tunisia. METHODS: The evaluation covered the period of 2012–2015 and used different data sources to measure indicators related to data quality and completeness, representativeness, timeliness, simplicity, acceptability, flexibility, stability and utility. RESULTS: During the evaluation period, 485.221 ILI cases were reported among 6.386.621 outpatients at 268 ILI sentinel sites. To conserve resources, cases were only enrolled and tested for influenza during times when the number of patients meeting the ILI case definition exceeded 7% (10% after 2014) of the total number of outpatients for the week. When this benchmark was met, five to 10 patients were enrolled and sampled by nasopharyngeal swabs the following week. In total, The National Influenza Center (NIC) received 2476 samples, of which 683 (27.6%) were positive for influenza. The greatest strength of the system was its representativeness and flexibility. The timeliness of the data and the acceptability of the surveillance system performed moderately well; however, the utility of the data and the stability and simplicity of the surveillance system need improvement. Overall, the performance of the Tunisian influenza surveillance system was evaluated as performing moderately well for situational awareness in the country and for collecting representative influenza virologic samples. CONCLUSIONS: The influenza surveillance system in Tunisia provided pertinent evidence for public health interventions related to influenza situational awareness. To better monitor influenza, we propose that ILI surveillance should be limited to sites that are currently performing well and the quality of data collected should be closely monitored and improved.",2019 Jun 6,"['Yazidi, Rihab', 'Aissi, Wafa', 'Bouguerra, Hind', 'Nouira, Mariem', 'Kharroubi, Ghassen', 'Maazaoui, Latifa', 'Zorraga, Mokhtar', 'Abdeddaiem, Naima', 'Chlif, Sadok', 'El Moussi, Awatef', 'Ben Hadj Kacem, Mohamed Ali', 'Snoussi, Mohamed Ali', 'Ghawar, Wissem', 'Koubaa, Makram', 'Polansky, Lauren', 'McCarron, Margaret', 'Boussarsar, Mohamed', 'Menif, Khaled', 'Amine, Slim', 'Ben Khelil, Jalila', 'Ben Jemaa, Mounir', 'Bettaieb, Jihene', 'Bouafif Ben Alaya, Nissaf', 'Ben Salah, Afif']",BMC Public Health,,,True
1664a9df618ca74e099245a2bd65f3172aeac284,PMC,Houttuynia cordata Thunb. and its bioactive compound 2-undecanone significantly suppress benzo(a)pyrene-induced lung tumorigenesis by activating the Nrf2-HO-1/NQO-1 signaling pathway,http://dx.doi.org/10.1186/s13046-019-1255-3,PMC6556055,31174565,CC BY,"BACKGROUND: Lung cancer remains the most common cause of cancer-related deaths, with a high incidence and mortality in both sexes worldwide. Chemoprevention has been the most effective strategy for lung cancer prevention. Thus, exploring novel and effective candidate agents with low toxicity for chemoprevention is essential and urgent. Houttuynia cordata Thunb. (Saururaceae) (H. cordata), which is a widely used herbal medicine and is also popularly consumed as a healthy vegetable, exhibits anti-inflammatory, antioxidant and antitumor activity. However, the chemopreventive effect of H. cordata against benzo(a)pyrene (B[a]P)-initiated lung tumorigenesis and the underlying mechanism remain unclear. METHODS: A B[a]P-stimulated lung adenocarcinoma animal model in A/J mice in vivo and a normal lung cell model (BEAS.2B) in vitro were established to investigate the chemopreventive effects of H. cordata and its bioactive compound 2-undecanone against lung tumorigenesis and to clarify the underlying mechanisms. RESULTS: H. cordata and 2-undecanone significantly suppressed B[a]P-induced lung tumorigenesis without causing obvious systemic toxicity in mice in vivo. Moreover, H. cordata and 2-undecanone effectively decreased B[a]P-induced intracellular reactive oxygen species (ROS) overproduction and further notably protected BEAS.2B cells from B[a]P-induced DNA damage and inflammation by significantly inhibiting phosphorylated H2A.X overexpression and interleukin-1β secretion. In addition, H. cordata and 2-undecanone markedly activated the Nrf2 pathway to induce the expression of the antioxidative enzymes heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO-1). Nrf2 silencing by transfection with Nrf2 siRNA markedly decreased the expression of HO-1 and NQO-1 to diminish the reductions in B[a]P-induced ROS overproduction, DNA damage and inflammation mediated by H. cordata and 2-undecanone. CONCLUSIONS: H. cordata and 2-undecanone could effectively activate the Nrf2-HO-1/NQO-1 signaling pathway to counteract intracellular ROS generation, thereby attenuating DNA damage and inflammation induced by B[a]P stimulation and playing a role in the chemoprevention of B[a]P-induced lung tumorigenesis. These findings provide new insight into the pharmacological action of H. cordata and indicate that H. cordata is a novel candidate agent for the chemoprevention of lung cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-019-1255-3) contains supplementary material, which is available to authorized users.",2019 Jun 7,"['Lou, Yanmei', 'Guo, Zhenzhen', 'Zhu, Yuanfeng', 'Kong, Muyan', 'Zhang, Rongrong', 'Lu, Linlin', 'Wu, Feichi', 'Liu, Zhongqiu', 'Wu, Jinjun']",J Exp Clin Cancer Res,,,True
f9187e3a34dfe7e63989291c32b4f8254de5e6a0,PMC,iProt-Sub: a comprehensive package for accurately mapping and predicting protease-specific substrates and cleavage sites,http://dx.doi.org/10.1093/bib/bby028,PMC6556904,29897410,CC BY,"Regulation of proteolysis plays a critical role in a myriad of important cellular processes. The key to better understanding the mechanisms that control this process is to identify the specific substrates that each protease targets. To address this, we have developed iProt-Sub, a powerful bioinformatics tool for the accurate prediction of protease-specific substrates and their cleavage sites. Importantly, iProt-Sub represents a significantly advanced version of its successful predecessor, PROSPER. It provides optimized cleavage site prediction models with better prediction performance and coverage for more species-specific proteases (4 major protease families and 38 different proteases). iProt-Sub integrates heterogeneous sequence and structural features and uses a two-step feature selection procedure to further remove redundant and irrelevant features in an effort to improve the cleavage site prediction accuracy. Features used by iProt-Sub are encoded by 11 different sequence encoding schemes, including local amino acid sequence profile, secondary structure, solvent accessibility and native disorder, which will allow a more accurate representation of the protease specificity of approximately 38 proteases and training of the prediction models. Benchmarking experiments using cross-validation and independent tests showed that iProt-Sub is able to achieve a better performance than several existing generic tools. We anticipate that iProt-Sub will be a powerful tool for proteome-wide prediction of protease-specific substrates and their cleavage sites, and will facilitate hypothesis-driven functional interrogation of protease-specific substrate cleavage and proteolytic events.",2018 Apr 19,"['Song, Jiangning', 'Wang, Yanan', 'Li, Fuyi', 'Akutsu, Tatsuya', 'Rawlings, Neil D', 'Webb, Geoffrey I', 'Chou, Kuo-Chen']",Brief Bioinform,,,True
9f2a5b356d46600dfa40b61958808eaaa105bef4,PMC,Forecasting national and regional influenza-like illness for the USA,http://dx.doi.org/10.1371/journal.pcbi.1007013,PMC6557527,31120881,CC BY,"Health planners use forecasts of key metrics associated with influenza-like illness (ILI); near-term weekly incidence, week of season onset, week of peak, and intensity of peak. Here, we describe our participation in a weekly prospective ILI forecasting challenge for the United States for the 2016-17 season and subsequent evaluation of our performance. We implemented a metapopulation model framework with 32 model variants. Variants differed from each other in their assumptions about: the force-of-infection (FOI); use of uninformative priors; the use of discounted historical data for not-yet-observed time points; and the treatment of regions as either independent or coupled. Individual model variants were chosen subjectively as the basis for our weekly forecasts; however, a subset of coupled models were only available part way through the season. Most frequently, during the 2016-17 season, we chose; FOI variants with both school vacations and humidity terms; uninformative priors; the inclusion of discounted historical data for not-yet-observed time points; and coupled regions (when available). Our near-term weekly forecasts substantially over-estimated incidence early in the season when coupled models were not available. However, our forecast accuracy improved in absolute terms and relative to other teams once coupled solutions were available. In retrospective analysis, we found that the 2016-17 season was not typical: on average, coupled models performed better when fit without historically augmented data. Also, we tested a simple ensemble model for the 2016-17 season and found that it underperformed our subjective choice for all forecast targets. In this study, we were able to improve accuracy during a prospective forecasting exercise by coupling dynamics between regions. Although reduction of forecast subjectivity should be a long-term goal, some degree of human intervention is likely to improve forecast accuracy in the medium-term in parallel with the systematic consideration of more sophisticated ensemble approaches.",2019 May 23,"['Ben-Nun, Michal', 'Riley, Pete', 'Turtle, James', 'Bacon, David P.', 'Riley, Steven']",PLoS Comput Biol,,,True
010244516e83fe8af1440b7223c4d8577d2787f3,PMC,Forecasting national and regional influenza-like illness for the USA,http://dx.doi.org/10.1371/journal.pcbi.1007013,PMC6557527,31120881,CC BY,"Health planners use forecasts of key metrics associated with influenza-like illness (ILI); near-term weekly incidence, week of season onset, week of peak, and intensity of peak. Here, we describe our participation in a weekly prospective ILI forecasting challenge for the United States for the 2016-17 season and subsequent evaluation of our performance. We implemented a metapopulation model framework with 32 model variants. Variants differed from each other in their assumptions about: the force-of-infection (FOI); use of uninformative priors; the use of discounted historical data for not-yet-observed time points; and the treatment of regions as either independent or coupled. Individual model variants were chosen subjectively as the basis for our weekly forecasts; however, a subset of coupled models were only available part way through the season. Most frequently, during the 2016-17 season, we chose; FOI variants with both school vacations and humidity terms; uninformative priors; the inclusion of discounted historical data for not-yet-observed time points; and coupled regions (when available). Our near-term weekly forecasts substantially over-estimated incidence early in the season when coupled models were not available. However, our forecast accuracy improved in absolute terms and relative to other teams once coupled solutions were available. In retrospective analysis, we found that the 2016-17 season was not typical: on average, coupled models performed better when fit without historically augmented data. Also, we tested a simple ensemble model for the 2016-17 season and found that it underperformed our subjective choice for all forecast targets. In this study, we were able to improve accuracy during a prospective forecasting exercise by coupling dynamics between regions. Although reduction of forecast subjectivity should be a long-term goal, some degree of human intervention is likely to improve forecast accuracy in the medium-term in parallel with the systematic consideration of more sophisticated ensemble approaches.",2019 May 23,"['Ben-Nun, Michal', 'Riley, Pete', 'Turtle, James', 'Bacon, David P.', 'Riley, Steven']",PLoS Comput Biol,,,False
2095bc88a4eeacff9b45a66ee1d4f1553fb184cf,PMC,Forecasting national and regional influenza-like illness for the USA,http://dx.doi.org/10.1371/journal.pcbi.1007013,PMC6557527,31120881,CC BY,"Health planners use forecasts of key metrics associated with influenza-like illness (ILI); near-term weekly incidence, week of season onset, week of peak, and intensity of peak. Here, we describe our participation in a weekly prospective ILI forecasting challenge for the United States for the 2016-17 season and subsequent evaluation of our performance. We implemented a metapopulation model framework with 32 model variants. Variants differed from each other in their assumptions about: the force-of-infection (FOI); use of uninformative priors; the use of discounted historical data for not-yet-observed time points; and the treatment of regions as either independent or coupled. Individual model variants were chosen subjectively as the basis for our weekly forecasts; however, a subset of coupled models were only available part way through the season. Most frequently, during the 2016-17 season, we chose; FOI variants with both school vacations and humidity terms; uninformative priors; the inclusion of discounted historical data for not-yet-observed time points; and coupled regions (when available). Our near-term weekly forecasts substantially over-estimated incidence early in the season when coupled models were not available. However, our forecast accuracy improved in absolute terms and relative to other teams once coupled solutions were available. In retrospective analysis, we found that the 2016-17 season was not typical: on average, coupled models performed better when fit without historically augmented data. Also, we tested a simple ensemble model for the 2016-17 season and found that it underperformed our subjective choice for all forecast targets. In this study, we were able to improve accuracy during a prospective forecasting exercise by coupling dynamics between regions. Although reduction of forecast subjectivity should be a long-term goal, some degree of human intervention is likely to improve forecast accuracy in the medium-term in parallel with the systematic consideration of more sophisticated ensemble approaches.",2019 May 23,"['Ben-Nun, Michal', 'Riley, Pete', 'Turtle, James', 'Bacon, David P.', 'Riley, Steven']",PLoS Comput Biol,,,False
ca17aaf789975ce5775a6a1ca9ab86b3b5beec30,PMC,Forecasting national and regional influenza-like illness for the USA,http://dx.doi.org/10.1371/journal.pcbi.1007013,PMC6557527,31120881,CC BY,"Health planners use forecasts of key metrics associated with influenza-like illness (ILI); near-term weekly incidence, week of season onset, week of peak, and intensity of peak. Here, we describe our participation in a weekly prospective ILI forecasting challenge for the United States for the 2016-17 season and subsequent evaluation of our performance. We implemented a metapopulation model framework with 32 model variants. Variants differed from each other in their assumptions about: the force-of-infection (FOI); use of uninformative priors; the use of discounted historical data for not-yet-observed time points; and the treatment of regions as either independent or coupled. Individual model variants were chosen subjectively as the basis for our weekly forecasts; however, a subset of coupled models were only available part way through the season. Most frequently, during the 2016-17 season, we chose; FOI variants with both school vacations and humidity terms; uninformative priors; the inclusion of discounted historical data for not-yet-observed time points; and coupled regions (when available). Our near-term weekly forecasts substantially over-estimated incidence early in the season when coupled models were not available. However, our forecast accuracy improved in absolute terms and relative to other teams once coupled solutions were available. In retrospective analysis, we found that the 2016-17 season was not typical: on average, coupled models performed better when fit without historically augmented data. Also, we tested a simple ensemble model for the 2016-17 season and found that it underperformed our subjective choice for all forecast targets. In this study, we were able to improve accuracy during a prospective forecasting exercise by coupling dynamics between regions. Although reduction of forecast subjectivity should be a long-term goal, some degree of human intervention is likely to improve forecast accuracy in the medium-term in parallel with the systematic consideration of more sophisticated ensemble approaches.",2019 May 23,"['Ben-Nun, Michal', 'Riley, Pete', 'Turtle, James', 'Bacon, David P.', 'Riley, Steven']",PLoS Comput Biol,,,False
58cc0f82a08e27b07e639ab9f001059841cc745b,PMC,Forecasting national and regional influenza-like illness for the USA,http://dx.doi.org/10.1371/journal.pcbi.1007013,PMC6557527,31120881,CC BY,"Health planners use forecasts of key metrics associated with influenza-like illness (ILI); near-term weekly incidence, week of season onset, week of peak, and intensity of peak. Here, we describe our participation in a weekly prospective ILI forecasting challenge for the United States for the 2016-17 season and subsequent evaluation of our performance. We implemented a metapopulation model framework with 32 model variants. Variants differed from each other in their assumptions about: the force-of-infection (FOI); use of uninformative priors; the use of discounted historical data for not-yet-observed time points; and the treatment of regions as either independent or coupled. Individual model variants were chosen subjectively as the basis for our weekly forecasts; however, a subset of coupled models were only available part way through the season. Most frequently, during the 2016-17 season, we chose; FOI variants with both school vacations and humidity terms; uninformative priors; the inclusion of discounted historical data for not-yet-observed time points; and coupled regions (when available). Our near-term weekly forecasts substantially over-estimated incidence early in the season when coupled models were not available. However, our forecast accuracy improved in absolute terms and relative to other teams once coupled solutions were available. In retrospective analysis, we found that the 2016-17 season was not typical: on average, coupled models performed better when fit without historically augmented data. Also, we tested a simple ensemble model for the 2016-17 season and found that it underperformed our subjective choice for all forecast targets. In this study, we were able to improve accuracy during a prospective forecasting exercise by coupling dynamics between regions. Although reduction of forecast subjectivity should be a long-term goal, some degree of human intervention is likely to improve forecast accuracy in the medium-term in parallel with the systematic consideration of more sophisticated ensemble approaches.",2019 May 23,"['Ben-Nun, Michal', 'Riley, Pete', 'Turtle, James', 'Bacon, David P.', 'Riley, Steven']",PLoS Comput Biol,,,False
7732ed94fb45c64d27fad1fad250e7937b3d4abc,PMC,Forecasting national and regional influenza-like illness for the USA,http://dx.doi.org/10.1371/journal.pcbi.1007013,PMC6557527,31120881,CC BY,"Health planners use forecasts of key metrics associated with influenza-like illness (ILI); near-term weekly incidence, week of season onset, week of peak, and intensity of peak. Here, we describe our participation in a weekly prospective ILI forecasting challenge for the United States for the 2016-17 season and subsequent evaluation of our performance. We implemented a metapopulation model framework with 32 model variants. Variants differed from each other in their assumptions about: the force-of-infection (FOI); use of uninformative priors; the use of discounted historical data for not-yet-observed time points; and the treatment of regions as either independent or coupled. Individual model variants were chosen subjectively as the basis for our weekly forecasts; however, a subset of coupled models were only available part way through the season. Most frequently, during the 2016-17 season, we chose; FOI variants with both school vacations and humidity terms; uninformative priors; the inclusion of discounted historical data for not-yet-observed time points; and coupled regions (when available). Our near-term weekly forecasts substantially over-estimated incidence early in the season when coupled models were not available. However, our forecast accuracy improved in absolute terms and relative to other teams once coupled solutions were available. In retrospective analysis, we found that the 2016-17 season was not typical: on average, coupled models performed better when fit without historically augmented data. Also, we tested a simple ensemble model for the 2016-17 season and found that it underperformed our subjective choice for all forecast targets. In this study, we were able to improve accuracy during a prospective forecasting exercise by coupling dynamics between regions. Although reduction of forecast subjectivity should be a long-term goal, some degree of human intervention is likely to improve forecast accuracy in the medium-term in parallel with the systematic consideration of more sophisticated ensemble approaches.",2019 May 23,"['Ben-Nun, Michal', 'Riley, Pete', 'Turtle, James', 'Bacon, David P.', 'Riley, Steven']",PLoS Comput Biol,,,True
4f4abb87fc3cfac784fdc7bf3c729d82a47e971c,PMC,Forecasting national and regional influenza-like illness for the USA,http://dx.doi.org/10.1371/journal.pcbi.1007013,PMC6557527,31120881,CC BY,"Health planners use forecasts of key metrics associated with influenza-like illness (ILI); near-term weekly incidence, week of season onset, week of peak, and intensity of peak. Here, we describe our participation in a weekly prospective ILI forecasting challenge for the United States for the 2016-17 season and subsequent evaluation of our performance. We implemented a metapopulation model framework with 32 model variants. Variants differed from each other in their assumptions about: the force-of-infection (FOI); use of uninformative priors; the use of discounted historical data for not-yet-observed time points; and the treatment of regions as either independent or coupled. Individual model variants were chosen subjectively as the basis for our weekly forecasts; however, a subset of coupled models were only available part way through the season. Most frequently, during the 2016-17 season, we chose; FOI variants with both school vacations and humidity terms; uninformative priors; the inclusion of discounted historical data for not-yet-observed time points; and coupled regions (when available). Our near-term weekly forecasts substantially over-estimated incidence early in the season when coupled models were not available. However, our forecast accuracy improved in absolute terms and relative to other teams once coupled solutions were available. In retrospective analysis, we found that the 2016-17 season was not typical: on average, coupled models performed better when fit without historically augmented data. Also, we tested a simple ensemble model for the 2016-17 season and found that it underperformed our subjective choice for all forecast targets. In this study, we were able to improve accuracy during a prospective forecasting exercise by coupling dynamics between regions. Although reduction of forecast subjectivity should be a long-term goal, some degree of human intervention is likely to improve forecast accuracy in the medium-term in parallel with the systematic consideration of more sophisticated ensemble approaches.",2019 May 23,"['Ben-Nun, Michal', 'Riley, Pete', 'Turtle, James', 'Bacon, David P.', 'Riley, Steven']",PLoS Comput Biol,,,False
73a2171fc7716dd485b9c3348902a7672213fc0a,PMC,ADAM17-dependent signaling is required for oncogenic human papillomavirus entry platform assembly,http://dx.doi.org/10.7554/eLife.44345,PMC6557631,31107240,CC BY,"Oncogenic human papillomaviruses (HPV) are small DNA viruses that infect keratinocytes. After HPV binding to cell surface receptors, a cascade of molecular interactions mediates the infectious cellular internalization of virus particles. Aside from the virus itself, important molecular players involved in virus entry include the tetraspanin CD151 and the epidermal growth factor receptor (EGFR). To date, it is unknown how these components are coordinated in space and time. Here, we studied plasma membrane dynamics of CD151 and EGFR and the HPV16 capsid during the early phase of infection. We find that the proteinase ADAM17 activates the extracellular signal-regulated kinases (ERK1/2) pathway by the shedding of growth factors which triggers the formation of an endocytic entry platform. Infectious endocytic entry platforms carrying virus particles consist of two-fold larger CD151 domains containing the EGFR. Our finding clearly dissects initial virus binding from ADAM17-dependent assembly of a HPV/CD151/EGFR entry platform.",,"['Mikuličić, Snježana', 'Finke, Jérôme', 'Boukhallouk, Fatima', 'Wüstenhagen, Elena', 'Sons, Dominik', 'Homsi, Yahya', 'Reiss, Karina', 'Lang, Thorsten', 'Florin, Luise']",eLife.; 8:e44345,,,True
5b37e0860765e5a82182e0420500001b1fede952,PMC,ADAM17-dependent signaling is required for oncogenic human papillomavirus entry platform assembly,http://dx.doi.org/10.7554/eLife.44345,PMC6557631,31107240,CC BY,"Oncogenic human papillomaviruses (HPV) are small DNA viruses that infect keratinocytes. After HPV binding to cell surface receptors, a cascade of molecular interactions mediates the infectious cellular internalization of virus particles. Aside from the virus itself, important molecular players involved in virus entry include the tetraspanin CD151 and the epidermal growth factor receptor (EGFR). To date, it is unknown how these components are coordinated in space and time. Here, we studied plasma membrane dynamics of CD151 and EGFR and the HPV16 capsid during the early phase of infection. We find that the proteinase ADAM17 activates the extracellular signal-regulated kinases (ERK1/2) pathway by the shedding of growth factors which triggers the formation of an endocytic entry platform. Infectious endocytic entry platforms carrying virus particles consist of two-fold larger CD151 domains containing the EGFR. Our finding clearly dissects initial virus binding from ADAM17-dependent assembly of a HPV/CD151/EGFR entry platform.",,"['Mikuličić, Snježana', 'Finke, Jérôme', 'Boukhallouk, Fatima', 'Wüstenhagen, Elena', 'Sons, Dominik', 'Homsi, Yahya', 'Reiss, Karina', 'Lang, Thorsten', 'Florin, Luise']",eLife.; 8:e44345,,,False
74bedf868bf72275e1d5a60150246aaae93d3be5,PMC,Development of a Novel Ex-vivo 3D Model to Screen Amoebicidal Activity on Infected Tissue,http://dx.doi.org/10.1038/s41598-019-44899-5,PMC6557822,31182753,CC BY,"Amoebiasis is a parasitic disease that causes thousands of deaths every year, its adverse effects and resistance to conventional treatments have led to the search of new treatment options, as well as the development of novel screening methods. In this work, we implemented a 3D model of intestine and liver slices from hamsters that were infected ex vivo with virulent E. histolytica trophozoites. Results show preserved histology in both uninfected tissues as well as ulcerations, destruction of the epithelial cells, and inflammatory reaction in intestine slices and formation of micro abscesses, and the presence of amoebae in the sinusoidal spaces and in the interior of central veins in liver slices. The three chemically synthetized compounds T-001, T-011, and T-016, which act as amoebicides in vitro, were active in both infected tissues, as they decreased the number of trophozoites, and provoked death by disintegration of the amoeba, similar to metronidazole. However, compound T-011 induced signs of cytotoxicity to liver slices. Our results suggest that ex vivo cultures of precision-cut intestinal and liver slices represent a reliable 3D approach to evaluate novel amoebicidal compounds, and to simultaneously detect their toxicity, while reducing the number of experimental animals commonly required by other model systems.",2019 Jun 10,"['Guzmán-Delgado, Nancy Elena', 'Carranza-Torres, Irma Edith', 'García-Davis, Sara', 'Rivera, Gildardo', 'Morán-Martínez, Javier', 'Betancourt-Martínez, Nadia Denys', 'Groothuis, G. M. M.', 'de Graaf, I. A. M.', 'Carranza-Rosales, Pilar']",Sci Rep,,,True
7a9a6baf1c4d04b23721c833ad956438f9d62e73,PMC,The MAP3K7-mTOR Axis Promotes the Proliferation and Malignancy of Hepatocellular Carcinoma Cells,http://dx.doi.org/10.3389/fonc.2019.00474,PMC6558008,31214512,CC BY,"Targeted therapy is currently limited for patients with hepatocellular carcinoma (HCC) due to the lack of suitable targets. Kinases play pivotal roles in many cellular biological processes, whereas dysregulation of kinases may lead to various diseases, particularly cancer. However, the role of kinases in HCC malignancy remains unclear. In this study, we employed a kinome small interfering RNA (siRNA) library, comprising 710 kinase-related genes, to screen whether any kinases were essential for cell proliferation in various HCC cell lines. Through a kinome siRNA library screening, we found that MAP3K7 was a crucial gene for HCC cell proliferation. Pharmacological or genetic ablation of MAP3K7 diminished the growth, migration, and invasion of HCC cells, including primary HCC cells. Stable knockdown of MAP3K7 attenuated tumor formation in a spheroid cell culture model and tumor xenograft mouse model. In addition, silencing MAP3K7 reduced the phosphorylation and expression of mammalian target of rapamycin (mTOR) in HCC cells. MAP3K7 expression was positively correlated with mTOR expression in tumors of patients with HCC. Higher co-expression of MAP3K7 and mTOR was significantly associated with poor prognosis of HCC. Taken together, our results revealed that the MAP3K7-mTOR axis might promote tumorigenesis and malignancy, which provides a potential marker or therapeutic target for HCC patients.",2019 Jun 4,"['Cheng, Jin-Shiung', 'Tsai, Wei-Lun', 'Liu, Pei-Feng', 'Goan, Yih-Gang', 'Lin, Chih-Wen', 'Tseng, Ho-Hsing', 'Lee, Cheng-Hsin', 'Shu, Chih-Wen']",Front Oncol,,,True
89f41c87c8849ce37e609c1010087291a4679a37,PMC,Outbreak analytics: a developing data science for informing the response to emerging pathogens,http://dx.doi.org/10.1098/rstb.2018.0276,PMC6558557,31104603,CC BY,"Despite continued efforts to improve health systems worldwide, emerging pathogen epidemics remain a major public health concern. Effective response to such outbreaks relies on timely intervention, ideally informed by all available sources of data. The collection, visualization and analysis of outbreak data are becoming increasingly complex, owing to the diversity in types of data, questions and available methods to address them. Recent advances have led to the rise of outbreak analytics, an emerging data science focused on the technological and methodological aspects of the outbreak data pipeline, from collection to analysis, modelling and reporting to inform outbreak response. In this article, we assess the current state of the field. After laying out the context of outbreak response, we critically review the most common analytics components, their inter-dependencies, data requirements and the type of information they can provide to inform operations in real time. We discuss some challenges and opportunities and conclude on the potential role of outbreak analytics for improving our understanding of, and response to outbreaks of emerging pathogens. This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control‘. This theme issue is linked with the earlier issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’.",2019 Jul 8,"['Polonsky, Jonathan A.', 'Baidjoe, Amrish', 'Kamvar, Zhian N.', 'Cori, Anne', 'Durski, Kara', 'Edmunds, W. John', 'Eggo, Rosalind M.', 'Funk, Sebastian', 'Kaiser, Laurent', 'Keating, Patrick', 'de Waroux, Olivier le Polain', 'Marks, Michael', 'Moraga, Paula', 'Morgan, Oliver', 'Nouvellet, Pierre', 'Ratnayake, Ruwan', 'Roberts, Chrissy H.', 'Whitworth, Jimmy', 'Jombart, Thibaut']",Philos Trans R Soc Lond B Biol Sci,,,True
d300bc4b7cec3731d56241c2de486cacdc23a37b,PMC,Transcriptome analysis of responses to bluetongue virus infection in Aedes albopictus cells,http://dx.doi.org/10.1186/s12866-019-1498-3,PMC6558886,31182015,CC BY,"BACKGROUND: Bluetongue virus (BTV) causes a disease among wild and domesticated ruminants which is not contagious, but which is transmitted by biting midges of the Culicoides species. BTV can induce an intense cytopathic effect (CPE) in mammalian cells after infection, although Culicoides- or mosquito-derived cell cultures cause non-lytic infection with BTV without CPE. However, little is known about the transcriptome changes in Aedes albopictus cells infected with BTV. METHODS: Transcriptome sequencing was used to identify the expression pattern of mRNA transcripts in A. albopictus cells infected with BTV, given the absence of the Culicoides genome sequence. Bioinformatics analyses were performed to examine the biological functions of the differentially expressed genes. Subsequently, quantitative reverse transcription–polymerase chain reaction was utilized to validate the sequencing data. RESULTS: In total, 51,850,205 raw reads were generated from the BTV infection group and 51,852,293 from the control group. A total of 5769 unigenes were common to both groups; only 779 unigenes existed exclusively in the infection group and 607 in the control group. In total, 380 differentially expressed genes were identified, 362 of which were up-regulated and 18 of which were down-regulated. Bioinformatics analyses revealed that the differentially expressed genes mainly participated in endocytosis, FoxO, MAPK, dorso-ventral axis formation, insulin resistance, Hippo, and JAK-STAT signaling pathways. CONCLUSION: This study represents the first attempt to investigate transcriptome-wide dysregulation in A. albopictus cells infected with BTV. The understanding of BTV pathogenesis and virus–vector interaction will be improved by global transcriptome profiling. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12866-019-1498-3) contains supplementary material, which is available to authorized users.",2019 Jun 10,"['Du, Junzheng', 'Gao, Shandian', 'Tian, Zhancheng', 'Guo, Yanni', 'Kang, Di', 'Xing, Shanshan', 'Zhang, Guorui', 'Liu, Guangyuan', 'Luo, Jianxun', 'Chang, Huiyun', 'Yin, Hong']",BMC Microbiol,,,True
4ed12286e237a4c8a78ce4de4e5a3e9a8cafe08b,PMC,Single organelle analysis to characterize mitochondrial function and crosstalk during viral infection,http://dx.doi.org/10.1038/s41598-019-44922-9,PMC6560178,31186476,CC BY,"Mitochondria are key for cellular metabolism and signalling processes during viral infection. We report a methodology to analyse mitochondrial properties at the single-organelle level during viral infection using a recombinant adenovirus coding for a mitochondrial tracer protein for tagging and detection by multispectral flow cytometry. Resolution at the level of tagged individual mitochondria revealed changes in mitochondrial size, membrane potential and displayed a fragile phenotype during viral infection of cells. Thus, single-organelle and multi-parameter resolution allows to explore altered energy metabolism and antiviral defence by tagged mitochondria selectively in virus-infected cells and will be instrumental to identify viral immune escape and to develop and monitor novel mitochondrial-targeted therapies.",2019 Jun 11,"['Schneider, Annika', 'Kurz, Sandra', 'Manske, Katrin', 'Janas, Marianne', 'Heikenwälder, Mathias', 'Misgeld, Thomas', 'Aichler, Michaela', 'Weissmann, Sebastian Felix', 'Zischka, Hans', 'Knolle, Percy', 'Wohlleber, Dirk']",Sci Rep,,,False
0dadaf875ce55724213796d3670ad73c5d8bd2a1,PMC,Single organelle analysis to characterize mitochondrial function and crosstalk during viral infection,http://dx.doi.org/10.1038/s41598-019-44922-9,PMC6560178,31186476,CC BY,"Mitochondria are key for cellular metabolism and signalling processes during viral infection. We report a methodology to analyse mitochondrial properties at the single-organelle level during viral infection using a recombinant adenovirus coding for a mitochondrial tracer protein for tagging and detection by multispectral flow cytometry. Resolution at the level of tagged individual mitochondria revealed changes in mitochondrial size, membrane potential and displayed a fragile phenotype during viral infection of cells. Thus, single-organelle and multi-parameter resolution allows to explore altered energy metabolism and antiviral defence by tagged mitochondria selectively in virus-infected cells and will be instrumental to identify viral immune escape and to develop and monitor novel mitochondrial-targeted therapies.",2019 Jun 11,"['Schneider, Annika', 'Kurz, Sandra', 'Manske, Katrin', 'Janas, Marianne', 'Heikenwälder, Mathias', 'Misgeld, Thomas', 'Aichler, Michaela', 'Weissmann, Sebastian Felix', 'Zischka, Hans', 'Knolle, Percy', 'Wohlleber, Dirk']",Sci Rep,,,True
e98b7f593cd7bdd1bff632f4770505561768b9c8,PMC,Quality of life reported by survivors after hospitalization for Middle East respiratory syndrome (MERS),http://dx.doi.org/10.1186/s12955-019-1165-2,PMC6560892,31186042,CC BY,"INTRODUCTION: Data are lacking on impact of Middle East Respiratory Syndrome (MERS) on health-related quality of life (HRQoL) among survivors. METHODS: We conducted a cross-sectional survey of MERS survivors who required hospitalization in Saudi Arabia during 2016–2017, approximately 1 year after diagnosis. The Short-Form General Health Survey 36 (SF-36) was administered by telephone interview to assess 8 quality of life domains for MERS survivors and a sample of survivors of severe acute respiratory infection (SARI) without MERS. We compared mean SF-36 scores of MERS and non-MERS SARI survivors using independent t-test, and compared categorical variables using chi-square test. Adjusted analyses were performed using multiple linear regression. RESULTS: Of 355 MERS survivors, 83 were eligible and 78 agreed to participate. MERS survivors were younger than non-MERS SARI survivors (mean ± SD): (44.9 years ±12.9) vs (50.0 years ±13.6), p = 0.031. Intensive care unit (ICU) admissions were similar for MERS and non-MERS SARI survivors (46.2% vs. 57.1%), p = 0.20. After adjusting for potential confounders, there were no significant differences between MERS and non-MERS SARI survivors in physical component or mental component summary scores. MERS ICU survivors scored lower than MERS survivors not admitted to an ICU for physical function (p = 0.05), general health (p = 0.01), vitality (p = 0.03), emotional role (p = 0.03) and physical component summary (p < 0.02). CONCLUSIONS: Functional scores were similar for MERS and non-MERS SARI survivors. However, MERS survivors of critical illness reported lower quality of life than survivors of less severe illness. Efforts are needed to address the long-term medical and psychological needs of MERS survivors.",2019 Jun 11,"['Batawi, Sarah', 'Tarazan, Nehal', 'Al-Raddadi, Rajaa', 'Al Qasim, Eman', 'Sindi, Anees', 'AL Johni, Sameera', 'Al-Hameed, Fahad M.', 'Arabi, Yaseen M.', 'Uyeki, Timothy M.', 'Alraddadi, Basem M.']",Health Qual Life Outcomes,,,True
98bf14e077d911ddc7450d48a7e79f3573d9e52a,PMC,"Incidence, Severity and Impact of Influenza: a joint meeting organised by the ISIRV Epidemiology Group and ECDC, Stockholm, 2019",http://dx.doi.org/10.2807/1560-7917.ES.2019.24.23.1900348,PMC6561017,31186076,CC BY,,2019 Jun 6,"['Rath, Barbara', 'Penttinen, Pasi']",Euro Surveill,,,True
e4c74e7b5b49aa74e2219f53fd0202f811cf85d6,PMC,Origins of Enterovirus Replication Organelles Established by Whole-Cell Electron Microscopy,http://dx.doi.org/10.1128/mBio.00951-19,PMC6561026,31186324,CC BY,"Enterovirus genome replication occurs at virus-induced structures derived from cellular membranes and lipids. However, the origin of these replication organelles (ROs) remains uncertain. Ultrastructural evidence of the membrane donor is lacking, suggesting that the sites of its transition into ROs are rare or fleeting. To overcome this challenge, we combined live-cell imaging and serial block-face scanning electron microscopy of whole cells to capture emerging enterovirus ROs. The first foci of fluorescently labeled viral protein correlated with ROs connected to the endoplasmic reticulum (ER) and preceded the appearance of ROs stemming from the trans-Golgi network. Whole-cell data sets further revealed striking contact regions between ROs and lipid droplets that may represent a route for lipid shuttling to facilitate RO proliferation and genome replication. Our data provide direct evidence that enteroviruses use ER and then Golgi membranes to initiate RO formation, demonstrating the remarkable flexibility with which enteroviruses usurp cellular organelles.",2019 Jun 11,"['Melia, Charlotte E.', 'Peddie, Christopher J.', 'de Jong, Anja W. M.', 'Snijder, Eric J.', 'Collinson, Lucy M.', 'Koster, Abraham J.', 'van der Schaar, Hilde M.', 'van Kuppeveld, Frank J. M.', 'Bárcena, Montserrat']",mBio,,,True
a50c402f6452315b8ee669802c6c96cc993586e5,PMC,Approaches to Interrogating the Human Memory B-Cell and Memory-Derived Antibody Repertoire Following Dengue Virus Infection,http://dx.doi.org/10.3389/fimmu.2019.01276,PMC6562360,31244836,CC BY,"Memory B-cells (MBCs) are potential antibody secreting immune cells that differentiate and mature following host exposure to a pathogen. Following differentiation, MBCs remain in peripheral circulation after recovery and are poised to secrete antigen-specific antibodies if and when they are re-exposed to their cognate antigen. Consequently, MBCs form the founder population and provide one of the first lines of pathogen-specific defense against reinfection. The role MBCs play is complicated for viruses that are heterologous, such as dengue virus (DENV), which exist as antigenically different serotypes. On second infection with a different serotype, MBCs from initial dengue infection rapidly proliferate and secrete antibodies: many of these MBC derived antibodies will be cross-reactive and weakly neutralizing, while some antibodies may recognize epitopes conserved across serotypes and have the capacity to broadly neutralize 2 or more serotypes. It is also possible that a new population of MBCs and antibodies specific for the second virus serotype need to arise for long-term broader immunity to develop. Methods to interrogate and track memory B cell responses are important for evaluating both natural immunity and vaccine response. However, the low abundance of MBCs for any specific pathogen makes it challenging to interrogate frequency, specificity, and breadth for the pathogen of interest. This review discusses current approaches that have been used to interrogate the memory B cell immune response against viral pathogens in general and DENV specifically. Including strengths, limitations, and future directions. Single-cell approaches could help uncover the DENV specific MBC antibody repertoire, and improved methods for isolating DENV specific monoclonal antibodies from human peripheral blood cells would allow for a functional analysis of the anti-DENV repertoire.",2019 Jun 6,"['Lyski, Zoe L.', 'Messer, William B.']",Front Immunol,,,True
3442b139e80c8351c89a9398709090db63edb8fe,PMC,"Seroprevalence of Rodent Pathogens in Wild Rats from the Island of St. Kitts, West Indies",http://dx.doi.org/10.3390/ani9050228,PMC6562389,31083284,CC BY,"SIMPLE SUMMARY: The role of rodents in the transmission of many diseases is widely known. Wild rats abundant in urban environments may transmit diseases to humans and other animals, including laboratory rodents used for biomedical research in research facilities, possibly compromising research data. In order to gather information about the various diseases present around such facilities, it is important to conduct routine surveillance of wild rodents in the area. In this pilot study, we surveyed 22 captured wild rats (Rattus norvegicus and Rattus rattus) from the Caribbean island of St. Kitts for 19 microorganisms. Information gained from such surveillance data would be beneficial in assessing regional public health risks and when implementing routine laboratory rodent health monitoring protocols. ABSTRACT: A pilot seroprevalence study was conducted to document exposure to selected pathogens in wild rats inhabiting the Caribbean island of St. Kitts. Serum samples collected from 22 captured wild rats (Rattus norvegicus and Rattus rattus) were tested for the presence of antibodies to various rodent pathogens using a rat MFI2 serology panel. The samples were positive for cilia-associated respiratory bacillus (13/22; 59.1%), Clostridium piliforme (4/22; 18.2%), Mycoplasma pulmonis (4/22; 18.2%), Pneumocystis carinii (1/22; 4.5%), mouse adenovirus type 2 (16/22; 72.7%), Kilham rat virus (15/22; 68.2%), reovirus type 3 (9/22; 40.9%), rat parvovirus (4/22; 18.2%), rat minute virus (4/22; 18.2%), rat theilovirus (2/22; 9.1%), and infectious diarrhea of infant rats strain of group B rotavirus (rat rotavirus) (1/22; 4.5%). This study provides the first evidence of exposure to various rodent pathogens in wild rats on the island of St. Kitts. Periodic pathogen surveillance in the wild rat population would be beneficial in assessing potential regional zoonotic risks as well as in enhancing the current knowledge when implementing routine animal health monitoring protocols in facilities with laboratory rodent colonies.",2019 May 10,"['Boey, Kenneth', 'Shiokawa, Kanae', 'Avsaroglu, Harutyun', 'Rajeev, Sreekumari']",Animals (Basel),,,True
e6a9cb9589ec2381d774a128189529fc2669f079,PMC,Viral Metagenomics on Cerebrospinal Fluid,http://dx.doi.org/10.3390/genes10050332,PMC6562652,31052348,CC BY,"Identifying the causative pathogen in central nervous system (CNS) infections is crucial for patient management and prognosis. Many viruses can cause CNS infections, yet screening for each individually is costly and time-consuming. Most metagenomic assays can theoretically detect all pathogens, but often fail to detect viruses because of their small genome and low viral load. Viral metagenomics overcomes this by enrichment of the viral genomic content in a sample. VIDISCA-NGS is one of the available workflows for viral metagenomics, which requires only a small input volume and allows multiplexing of multiple samples per run. The performance of VIDISCA-NGS was tested on 45 cerebrospinal fluid (CSF) samples from patients with suspected CNS infections in which a virus was identified and quantified by polymerase chain reaction. Eighteen were positive for an RNA virus, and 34 for a herpesvirus. VIDISCA-NGS detected all RNA viruses with a viral load >2 × 10(4) RNA copies/mL (n = 6) and 8 of 12 of the remaining low load samples. Only one herpesvirus was identified by VIDISCA-NGS, however, when withholding a DNase treatment, 11 of 18 samples with a herpesvirus load >10(4) DNA copies/mL were detected. Our results indicate that VIDISCA-NGS has the capacity to detect low load RNA viruses in CSF. Herpesvirus DNA in clinical samples is probably non-encapsidated and therefore difficult to detect by VIDISCA-NGS.",2019 Apr 30,"['Edridge, Arthur W. D.', 'Deijs, Martin', 'van Zeggeren, Ingeborg E.', 'Kinsella, Cormac M.', 'Jebbink, Maarten F.', 'Bakker, Margreet', 'van de Beek, Diederik', 'Brouwer, Matthijs C.', 'van der Hoek, Lia']",Genes (Basel),,,True
43965ccebe844c1ea4ae725565b0d326d732fce0,PMC,Viral Metagenomics on Cerebrospinal Fluid,http://dx.doi.org/10.3390/genes10050332,PMC6562652,31052348,CC BY,"Identifying the causative pathogen in central nervous system (CNS) infections is crucial for patient management and prognosis. Many viruses can cause CNS infections, yet screening for each individually is costly and time-consuming. Most metagenomic assays can theoretically detect all pathogens, but often fail to detect viruses because of their small genome and low viral load. Viral metagenomics overcomes this by enrichment of the viral genomic content in a sample. VIDISCA-NGS is one of the available workflows for viral metagenomics, which requires only a small input volume and allows multiplexing of multiple samples per run. The performance of VIDISCA-NGS was tested on 45 cerebrospinal fluid (CSF) samples from patients with suspected CNS infections in which a virus was identified and quantified by polymerase chain reaction. Eighteen were positive for an RNA virus, and 34 for a herpesvirus. VIDISCA-NGS detected all RNA viruses with a viral load >2 × 10(4) RNA copies/mL (n = 6) and 8 of 12 of the remaining low load samples. Only one herpesvirus was identified by VIDISCA-NGS, however, when withholding a DNase treatment, 11 of 18 samples with a herpesvirus load >10(4) DNA copies/mL were detected. Our results indicate that VIDISCA-NGS has the capacity to detect low load RNA viruses in CSF. Herpesvirus DNA in clinical samples is probably non-encapsidated and therefore difficult to detect by VIDISCA-NGS.",2019 Apr 30,"['Edridge, Arthur W. D.', 'Deijs, Martin', 'van Zeggeren, Ingeborg E.', 'Kinsella, Cormac M.', 'Jebbink, Maarten F.', 'Bakker, Margreet', 'van de Beek, Diederik', 'Brouwer, Matthijs C.', 'van der Hoek, Lia']",Genes (Basel),,,False
861fcade6995d79dfc98e9a584edc8cdd779324d,PMC,Regulation of Ribosomal Proteins on Viral Infection,http://dx.doi.org/10.3390/cells8050508,PMC6562653,31137833,CC BY,"Ribosomal proteins (RPs), in conjunction with rRNA, are major components of ribosomes involved in the cellular process of protein biosynthesis, known as “translation”. The viruses, as the small infectious pathogens with limited genomes, must recruit a variety of host factors to survive and propagate, including RPs. At present, more and more information is available on the functional relationship between RPs and virus infection. This review focuses on advancements in my own understanding of critical roles of RPs in the life cycle of viruses. Various RPs interact with viral mRNA and proteins to participate in viral protein biosynthesis and regulate the replication and infection of virus in host cells. Most interactions are essential for viral translation and replication, which promote viral infection and accumulation, whereas the minority represents the defense signaling of host cells by activating immune pathway against virus. RPs provide a new platform for antiviral therapy development, however, at present, antiviral therapeutics with RPs involving in virus infection as targets is limited, and exploring antiviral strategy based on RPs will be the guides for further study.",2019 May 27,"Li, Shuo",Cells,,,True
9a283bfd56827aac7e25105d2d9488714de7769a,PMC,Chapparvovirus DNA Found in 4% of Dogs with Diarrhea,http://dx.doi.org/10.3390/v11050398,PMC6563200,31035625,CC BY,"Feces from dogs in an unexplained outbreak of diarrhea were analyzed by viral metagenomics revealing the genome of a novel parvovirus. The parvovirus was named cachavirus and was classified within the proposed Chapparvovirus genus. Using PCR, cachavirus DNA was detected in two of nine tested dogs from that outbreak. In order to begin to elucidate the clinical impact of this virus, 2,053 canine fecal samples were screened using real-time PCR. Stool samples from 203 healthy dogs were positive for cachavirus DNA at a rate of 1.47%, while 802 diarrhea samples collected in 2017 and 964 samples collected in 2018 were positive at rates of 4.0% and 4.66% frequencies, respectively (healthy versus 2017-2018 combined diarrhea p-value of 0.05). None of 83 bloody diarrhea samples tested positive. Viral loads were generally low with average real-time PCR Ct values of 36 in all three positive groups. The species tropism and pathogenicity of cachavirus, the first chapparvovirus reported in feces of a placental carnivore, remains to be fully determined.",2019 Apr 27,"['Fahsbender, Elizabeth', 'Altan, Eda', 'Seguin, M. Alexis', 'Young, Pauline', 'Estrada, Marko', 'Leutenegger, Christian', 'Delwart, Eric']",Viruses,,,True
3d688a6421aa6f09817bccba18d9a5f60beb95b6,PMC,Chapparvovirus DNA Found in 4% of Dogs with Diarrhea,http://dx.doi.org/10.3390/v11050398,PMC6563200,31035625,CC BY,"Feces from dogs in an unexplained outbreak of diarrhea were analyzed by viral metagenomics revealing the genome of a novel parvovirus. The parvovirus was named cachavirus and was classified within the proposed Chapparvovirus genus. Using PCR, cachavirus DNA was detected in two of nine tested dogs from that outbreak. In order to begin to elucidate the clinical impact of this virus, 2,053 canine fecal samples were screened using real-time PCR. Stool samples from 203 healthy dogs were positive for cachavirus DNA at a rate of 1.47%, while 802 diarrhea samples collected in 2017 and 964 samples collected in 2018 were positive at rates of 4.0% and 4.66% frequencies, respectively (healthy versus 2017-2018 combined diarrhea p-value of 0.05). None of 83 bloody diarrhea samples tested positive. Viral loads were generally low with average real-time PCR Ct values of 36 in all three positive groups. The species tropism and pathogenicity of cachavirus, the first chapparvovirus reported in feces of a placental carnivore, remains to be fully determined.",2019 Apr 27,"['Fahsbender, Elizabeth', 'Altan, Eda', 'Seguin, M. Alexis', 'Young, Pauline', 'Estrada, Marko', 'Leutenegger, Christian', 'Delwart, Eric']",Viruses,,,False
63c22b2cf82f4e4e9942d252fc33975a6db4d0d2,PMC,Human Hepatitis B Virus Core Protein Inhibits IFNα-Induced IFITM1 Expression by Interacting with BAF200,http://dx.doi.org/10.3390/v11050427,PMC6563218,31075894,CC BY,"Human hepatitis B virus core protein (HBc) is a structural protein of the hepatitis B virus (HBV) and contributes to HBV regulation of host-cell transcription. However, the mechanisms of transcriptional regulation remain poorly characterized. To dissect the function of HBc, a yeast two-hybrid was performed to identify HBc-binding proteins, and the C-terminal of BRG1/hBRM-associated factors 200 (BAF200C) was identified. Then, the existence of HBc interactions with BAF200C and full-length BAF200 was confirmed via co-immunoprecipitation assays in 293T, HepG2 and HepG2-NTCP cells. Furthermore, we show that the binding between HBc and BAF200 was of vital importance to HBc mediated downregulation of interferon-induced transmembrane protein 1 (IFITM1) expression, and the mechanisms for the downregulation were disclosed as follows. Basal level of IFITM1 expression depends on BAF200, rather than the JAK–STAT1 pathway. The interaction of HBc with BAF200 disturbs the stability of the polybromo-associated BAF (PBAF) complex and results in the suppression of IFTM1 transcription. Finally, the antiviral effects of IFITM1 on cell proliferation and HBV replication were found to be partially restored when HBc was co-transfected with BAF200. Collectively, our findings indicate that HBc plays a role in HBV resistance against the antiviral activities of IFNα, providing details about HBV evasion of host innate immunity.",2019 May 9,"['Li, Tongya', 'Ke, Zunlong', 'Liu, Weiyong', 'Xiong, Ying', 'Zhu, Ying', 'Liu, Yingle']",Viruses,,,True
a1efb6bb6211fc7190f9e06ac0929d340e7aafa1,PMC,Efficient Production of Human Norovirus-Specific IgY in Egg Yolks by Vaccination of Hens with a Recombinant Vesicular Stomatitis Virus Expressing VP1 Protein,http://dx.doi.org/10.3390/v11050444,PMC6563233,31100802,CC BY,"Human norovirus (HuNoV) is responsible for more than 95% of outbreaks of acute nonbacterial gastroenteritis worldwide. Despite major efforts, there are no vaccines or effective therapeutic interventions against this virus. Chicken immunoglobulin Y (IgY)-based passive immunization has been shown to be an effective strategy to prevent and treat many enteric viral diseases. Here, we developed a highly efficient bioreactor to generate high titers of HuNoV-specific IgY in chicken yolks using a recombinant vesicular stomatitis virus expressing HuNoV capsid protein (rVSV-VP1) as an antigen. We first demonstrated that HuNoV VP1 protein was highly expressed in chicken cells infected by rVSV-VP1. Subsequently, we found that White Leghorn hens immunized intramuscularly with rVSV-VP1 triggered a high level of HuNoV-specific yolk IgY antibodies. The purified yolk IgY was efficiently recognized by HuNoV virus-like particles (VLPs). Importantly, HuNoV-specific IgY efficiently blocked the binding of HuNoV VLPs to all three types (A, B, and O) of histo-blood group antigens (HBGAs), the attachment factors for HuNoV. In addition, the receptor blocking activity of IgY remained stable at temperature below 70 °C and at pH ranging from 4 to 9. Thus, immunization of hens with VSV-VP1 could be a cost-effective and practical strategy for large-scale production of anti-HuNoV IgY antibodies for potential use as prophylactic and therapeutic treatment against HuNoV infection.",2019 May 16,"['Zhu, Yang', 'Ma, Yuanmei', 'Lu, Mijia', 'Zhang, Yu', 'Li, Anzhong', 'Liang, Xueya', 'Li, Jianrong']",Viruses,,,True
dcd6d893dd1fcb8bd484691ccdb9043f3b2d9934,PMC,Extracellular Vesicles and Ebola Virus: A New Mechanism of Immune Evasion,http://dx.doi.org/10.3390/v11050410,PMC6563240,31052499,CC BY,"Ebola virus (EBOV) disease can result in a range of symptoms anywhere from virtually asymptomatic to severe hemorrhagic fever during acute infection. Additionally, spans of asymptomatic persistence in recovering survivors is possible, during which transmission of the virus may occur. In acute infection, substantial cytokine storm and bystander lymphocyte apoptosis take place, resulting in uncontrolled, systemic inflammation in affected individuals. Recently, studies have demonstrated the presence of EBOV proteins VP40, glycoprotein (GP), and nucleoprotein (NP) packaged into extracellular vesicles (EVs) during infection. EVs containing EBOV proteins have been shown to induce apoptosis in recipient immune cells, as well as contain pro-inflammatory cytokines. In this manuscript, we review the current field of knowledge on EBOV EVs including the mechanisms of their biogenesis, their cargo and their effects in recipient cells. Furthermore, we discuss some of the effects that may be induced by EBOV EVs that have not yet been characterized and highlight the remaining questions and future directions.",2019 May 2,"['Pleet, Michelle L.', 'DeMarino, Catherine', 'Stonier, Spencer W.', 'Dye, John M.', 'Jacobson, Steven', 'Aman, M. Javad', 'Kashanchi, Fatah']",Viruses,,,True
c73992ad20d48db3c7d34e9c85bff5e541598691,PMC,Animals as Reservoir for Human Norovirus,http://dx.doi.org/10.3390/v11050478,PMC6563253,31130647,CC BY,"Norovirus is the most common cause of non-bacterial gastroenteritis and is a burden worldwide. The increasing norovirus diversity is currently categorized into at least 10 genogroups which are further classified into more than 40 genotypes. In addition to humans, norovirus can infect a broad range of hosts including livestock, pets, and wild animals, e.g., marine mammals and bats. Little is known about norovirus infections in most non-human hosts, but the close genetic relatedness between some animal and human noroviruses coupled with lack of understanding where newly appearing human norovirus genotypes and variants are emerging from has led to the hypothesis that norovirus may not be host restricted and might be able to jump the species barrier. We have systematically reviewed the literature to describe the diversity, prevalence, and geographic distribution of noroviruses found in animals, and the pathology associated with infection. We further discuss the evidence that exists for or against interspecies transmission including surveillance data and data from in vitro and in vivo experiments.",2019 May 25,"['Villabruna, Nele', 'Koopmans, Marion P. G.', 'de Graaf, Miranda']",Viruses,,,True
da77b57aa291d1174c30c2e07f56ec327564fb54,PMC,Animals as Reservoir for Human Norovirus,http://dx.doi.org/10.3390/v11050478,PMC6563253,31130647,CC BY,"Norovirus is the most common cause of non-bacterial gastroenteritis and is a burden worldwide. The increasing norovirus diversity is currently categorized into at least 10 genogroups which are further classified into more than 40 genotypes. In addition to humans, norovirus can infect a broad range of hosts including livestock, pets, and wild animals, e.g., marine mammals and bats. Little is known about norovirus infections in most non-human hosts, but the close genetic relatedness between some animal and human noroviruses coupled with lack of understanding where newly appearing human norovirus genotypes and variants are emerging from has led to the hypothesis that norovirus may not be host restricted and might be able to jump the species barrier. We have systematically reviewed the literature to describe the diversity, prevalence, and geographic distribution of noroviruses found in animals, and the pathology associated with infection. We further discuss the evidence that exists for or against interspecies transmission including surveillance data and data from in vitro and in vivo experiments.",2019 May 25,"['Villabruna, Nele', 'Koopmans, Marion P. G.', 'de Graaf, Miranda']",Viruses,,,True
fe8673fd11cb2de090872b54b123acd6610ebfd1,PMC,"The Utility of Data Transformation for Alignment, De Novo Assembly and Classification of Short Read Virus Sequences",http://dx.doi.org/10.3390/v11050394,PMC6563281,31035503,CC BY,"Advances in DNA sequencing technology are facilitating genomic analyses of unprecedented scope and scale, widening the gap between our abilities to generate and fully exploit biological sequence data. Comparable analytical challenges are encountered in other data-intensive fields involving sequential data, such as signal processing, in which dimensionality reduction (i.e., compression) methods are routinely used to lessen the computational burden of analyses. In this work, we explored the application of dimensionality reduction methods to numerically represent high-throughput sequence data for three important biological applications of virus sequence data: reference-based mapping, short sequence classification and de novo assembly. Leveraging highly compressed sequence transformations to accelerate sequence comparison, our approach yielded comparable accuracy to existing approaches, further demonstrating its suitability for sequences originating from diverse virus populations. We assessed the application of our methodology using both synthetic and real viral pathogen sequences. Our results show that the use of highly compressed sequence approximations can provide accurate results, with analytical performance retained and even enhanced through appropriate dimensionality reduction of sequence data.",2019 Apr 26,"['Tapinos, Avraam', 'Constantinides, Bede', 'Phan, My V. T.', 'Kouchaki, Samaneh', 'Cotten, Matthew', 'Robertson, David L.']",Viruses,,,True
534a301ea6a76eb47c8d42e30981088ac5603418,PMC,Coxsackievirus B3 Responds to Polyamine Depletion via Enhancement of 2A and 3C Protease Activity,http://dx.doi.org/10.3390/v11050403,PMC6563312,31052199,CC BY,"Polyamines are small positively-charged molecules abundant in eukaryotic cells that are crucial to RNA virus replication. In eukaryotic cells, polyamines facilitate processes such as transcription, translation, and DNA replication, and viruses similarly rely on polyamines to facilitate transcription and translation. Whether polyamines function at additional stages in viral replication remains poorly understood. Picornaviruses, including Coxsackievirus B3 (CVB3), are sensitive to polyamine depletion both in vitro and in vivo; however, precisely how polyamine function in picornavirus infection has not been described. Here, we describe CVB3 mutants that arise with passage in polyamine-depleted conditions. We observe mutations in the 2A and 3C proteases, and we find that these mutant proteases confer resistance to polyamine depletion. Using a split luciferase reporter system to measure protease activity, we determined that polyamines facilitate viral protease activity. We further observe that the 2A and 3C protease mutations enhance reporter protease activity in polyamine-depleted conditions. Finally, we find that these mutations promote cleavage of cellular eIF4G during infection of polyamine-depleted cells. In sum, our results suggest that polyamines are crucial to protease function during picornavirus infection. Further, these data highlight viral proteases as potential antiviral targets and highlight how CVB3 may overcome polyamine-depleting antiviral therapies.",2019 Apr 30,"['Dial, Courtney N.', 'Tate, Patrick M.', 'Kicmal, Thomas M.', 'Mounce, Bryan C.']",Viruses,,,True
588bebe109353fc242f41c7655aa3bf906cecc3f,PMC,Novel Bat Alphacoronaviruses in Southern China Support Chinese Horseshoe Bats as an Important Reservoir for Potential Novel Coronaviruses,http://dx.doi.org/10.3390/v11050423,PMC6563315,31067830,CC BY,"While bats are increasingly recognized as a source of coronavirus epidemics, the diversity and emergence potential of bat coronaviruses remains to be fully understood. Among 1779 bat samples collected in China, diverse coronaviruses were detected in 32 samples from five different bat species by RT-PCR. Two novel alphacoronaviruses, Rhinolophus sinicus bat coronavirus HKU32 (Rs-BatCoV HKU32) and Tylonycteris robustula bat coronavirus HKU33 (Tr-BatCoV HKU33), were discovered from Chinese horseshoe bats in Hong Kong and greater bamboo bats in Guizhou Province, respectively. Genome analyses showed that Rs-BatCoV HKU32 is closely related to BatCoV HKU10 and related viruses from diverse bat families, whereas Tr-BatCoV HKU33 is closely related to BtNv-AlphaCoV and similar viruses exclusively from bats of Vespertilionidae family. The close relatedness of Rs-BatCoV HKU32 to BatCoV HKU10 which was also detected in Pomona roundleaf bats from the same country park suggests that these viruses may have the tendency of infecting genetically distant bat populations of close geographical proximity with subsequent genetic divergence. Moreover, the presence of SARSr-CoV ORF7a-like protein in Rs-BatCoV HKU32 suggests a common evolutionary origin of this accessory protein with SARS-CoV, also from Chinese horseshoe bats, an apparent reservoir for coronavirus epidemics. The emergence potential of Rs-BatCoV HKU32 should be explored.",2019 May 7,"['Lau, Susanna K.P.', 'Wong, Antonio C.P.', 'Zhang, Libao', 'Luk, Hayes K.H.', 'Kwok, Jamie S. L.', 'Ahmed, Syed S.', 'Cai, Jian-Piao', 'Zhao, Pyrear S.H.', 'Teng, Jade L.L.', 'Tsui, Stephen K.W.', 'Yuen, Kwok-Yung', 'Woo, Patrick C. Y.']",Viruses,,,True
33b0c24cb03b515296b278e96fd7de32151b9511,PMC,Exploiting the Legacy of the Arbovirus Hunters,http://dx.doi.org/10.3390/v11050471,PMC6563318,31126128,CC BY,"In recent years, it has become evident that a generational gap has developed in the community of arbovirus research. This apparent gap is due to the dis-investment of training for the next generation of arbovirologists, which threatens to derail the rich history of virus discovery, field epidemiology, and understanding of the richness of diversity that surrounds us. On the other hand, new technologies have resulted in an explosion of virus discovery that is constantly redefining the virosphere and the evolutionary relationships between viruses. This paradox presents new challenges that may have immediate and disastrous consequences for public health when yet to be discovered arboviruses emerge. In this review we endeavor to bridge this gap by providing a historical context for the work being conducted today and provide continuity between the generations. To this end, we will provide a narrative of the thrill of scientific discovery and excitement and the challenges lying ahead.",2019 May 23,"['Vasilakis, Nikos', 'Tesh, Robert B.', 'Popov, Vsevolod L.', 'Widen, Steve G.', 'Wood, Thomas G.', 'Forrester, Naomi L.', 'Gonzalez, Jean Paul', 'Saluzzo, Jean Francois', 'Alkhovsky, Sergey', 'Lam, Sai Kit', 'Mackenzie, John S.', 'Walker, Peter J.']",Viruses,,,True
b4ad07853c3096e4d3ab03e09b076aea8d137956,PMC,Exploiting the Legacy of the Arbovirus Hunters,http://dx.doi.org/10.3390/v11050471,PMC6563318,31126128,CC BY,"In recent years, it has become evident that a generational gap has developed in the community of arbovirus research. This apparent gap is due to the dis-investment of training for the next generation of arbovirologists, which threatens to derail the rich history of virus discovery, field epidemiology, and understanding of the richness of diversity that surrounds us. On the other hand, new technologies have resulted in an explosion of virus discovery that is constantly redefining the virosphere and the evolutionary relationships between viruses. This paradox presents new challenges that may have immediate and disastrous consequences for public health when yet to be discovered arboviruses emerge. In this review we endeavor to bridge this gap by providing a historical context for the work being conducted today and provide continuity between the generations. To this end, we will provide a narrative of the thrill of scientific discovery and excitement and the challenges lying ahead.",2019 May 23,"['Vasilakis, Nikos', 'Tesh, Robert B.', 'Popov, Vsevolod L.', 'Widen, Steve G.', 'Wood, Thomas G.', 'Forrester, Naomi L.', 'Gonzalez, Jean Paul', 'Saluzzo, Jean Francois', 'Alkhovsky, Sergey', 'Lam, Sai Kit', 'Mackenzie, John S.', 'Walker, Peter J.']",Viruses,,,False
8249b9b7e4846415737d263b7187056c4733ba39,PMC,The Third Annual Meeting of the European Virus Bioinformatics Center,http://dx.doi.org/10.3390/v11050420,PMC6563321,31060321,CC BY,"The Third Annual Meeting of the European Virus Bioinformatics Center (EVBC) took place in Glasgow, United Kingdom, 28–29 March 2019. Virus bioinformatics has become central to virology research, and advances in bioinformatics have led to improved approaches to investigate viral infections and outbreaks, being successfully used to detect, control, and treat infections of humans and animals. This active field of research has attracted approximately 110 experts in virology and bioinformatics/computational biology from Europe and other parts of the world to attend the two-day meeting in Glasgow to increase scientific exchange between laboratory- and computer-based researchers. The meeting was held at the McIntyre Building of the University of Glasgow; a perfect location, as it was originally built to be a place for “rubbing your brains with those of other people”, as Rector Stanley Baldwin described it. The goal of the meeting was to provide a meaningful and interactive scientific environment to promote discussion and collaboration and to inspire and suggest new research directions and questions. The meeting featured eight invited and twelve contributed talks, on the four main topics: (1) systems virology, (2) virus-host interactions and the virome, (3) virus classification and evolution and (4) epidemiology, surveillance and evolution. Further, the meeting featured 34 oral poster presentations, all of which focused on specific areas of virus bioinformatics. This report summarizes the main research findings and highlights presented at the meeting.",2019 May 5,"['Hufsky, Franziska', 'Ibrahim, Bashar', 'Modha, Sejal', 'Clokie, Martha R. J.', 'Deinhardt-Emmer, Stefanie', 'Dutilh, Bas E.', 'Lycett, Samantha', 'Simmonds, Peter', 'Thiel, Volker', 'Abroi, Aare', 'Adriaenssens, Evelien M.', 'Escalera-Zamudio, Marina', 'Kelly, Jenna Nicole', 'Lamkiewicz, Kevin', 'Lu, Lu', 'Susat, Julian', 'Sicheritz, Thomas', 'Robertson, David L.', 'Marz, Manja']",Viruses,,,True
41baca2bc5af0758c336c9b56d09a5f95c7afcae,PMC,Antiviral RNAi in Insects and Mammals: Parallels and Differences,http://dx.doi.org/10.3390/v11050448,PMC6563508,31100912,CC BY,"The RNA interference (RNAi) pathway is a potent antiviral defense mechanism in plants and invertebrates, in response to which viruses evolved suppressors of RNAi. In mammals, the first line of defense is mediated by the type I interferon system (IFN); however, the degree to which RNAi contributes to antiviral defense is still not completely understood. Recent work suggests that antiviral RNAi is active in undifferentiated stem cells and that antiviral RNAi can be uncovered in differentiated cells in which the IFN system is inactive or in infections with viruses lacking putative viral suppressors of RNAi. In this review, we describe the mechanism of RNAi and its antiviral functions in insects and mammals. We draw parallels and highlight differences between (antiviral) RNAi in these classes of animals and discuss open questions for future research.",2019 May 16,"['Schuster, Susan', 'Miesen, Pascal', 'van Rij, Ronald P.']",Viruses,,,True
a25c99e62ee57a207f77bcba9f484a2416f11849,PMC,"Characteristics of the Life Cycle of Porcine Deltacoronavirus (PDCoV) In Vitro: Replication Kinetics, Cellular Ultrastructure and Virion Morphology, and Evidence of Inducing Autophagy",http://dx.doi.org/10.3390/v11050455,PMC6563515,31109068,CC BY,"Porcine deltacoronavirus (PDCoV) causes severe diarrhea and vomiting in affected piglets. The aim of this study was to establish the basic, in vitro characteristics of the life cycle such as replication kinetics, cellular ultrastructure, virion morphology, and induction of autophagy of PDCoV. Time-course analysis of viral subgenomic and genomic RNA loads and infectious titers indicated that one replication cycle of PDCoV takes 5 to 6 h. Electron microscopy showed that PDCoV infection induced the membrane rearrangements with double-membrane vesicles and large virion-containing vacuoles. The convoluted membranes structures described in alpha- and beta-coronavirus were not observed. PDCoV infection also increased the number of autophagosome-like vesicles in the cytoplasm of cells, and the autophagy response was detected by LC3 I/II and p62 Western blot analysis. For the first time, this study presents the picture of the PDCoV infection cycle, which is crucial to help elucidate the molecular mechanism of deltacoronavirus replication.",2019 May 18,"['Qin, Pan', 'Du, En-Zhong', 'Luo, Wen-Ting', 'Yang, Yong-Le', 'Zhang, Yu-Qi', 'Wang, Bin', 'Huang, Yao-Wei']",Viruses,,,True
e066a2eab75d8d421fe141176355bcbabc52b4fd,PMC,Epidemiology of respiratory infections among adults in Qatar (2012-2017),http://dx.doi.org/10.1371/journal.pone.0218097,PMC6563968,31194775,CC BY,"BACKGROUND: Limited data is available about the etiology of influenza like illnesses (ILIs) in Qatar. OBJECTIVES: This study aimed at providing preliminary estimates of influenza and other respiratory infections circulating among adults in Qatar. METHODS: We retrospectively collected data of about 44,000 patients who visited Hamad General Hospital clinics, sentinel sites, and all primary healthcare centers in Qatar between 2012 and 2017. All samples were tested for influenza viruses, whereas about 38,000 samples were tested for influenza and a panel of respiratory viruses using Fast Track Diagnostics (FTD) RT-PCR kit. RESULTS: Among all ILIs cases, 20,278 (46.5%) tested positive for at least one respiratory pathogen. Influenza virus was predominating (22.6%), followed by human rhinoviruses (HRVs) (9.5%), and human coronaviruses (HCoVs) (5%). A detection rate of 2–3% was recorded for mycoplasma pneumonia, adenoviruses, human parainfluenza viruses (HPIVs), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV). ILIs cases were reported throughout the year, however, influenza, RSV, and HMPV exhibited strong seasonal peaks in the winter, while HRVs circulated more during fall and spring. Elderly (>50 years) had the lowest rates of influenza A (13.9%) and B (4.2%), while presenting the highest rates of RSV (3.4%) and HMPV (3.3%). While males had higher rates of HRVs (11.9%), enteroviruses (1.1%) and MERS CoV (0.2%), females had higher proportions of influenza (26.3%), HPIVs (3.2%) and RSV (3.6%) infections. CONCLUSION: This report provides a comprehensive insight about the epidemiology of ILIs among adults in the Qatar, as a representative of Gulf States. These results would help in improvement and optimization of diagnostic procedures, as well as control and prevention of the respiratory infections.",2019 Jun 13,"['Al-Romaihi, Hamad Eid', 'Smatti, Maria K.', 'Ganesan, Nandakumar', 'Nadeem, Shazia', 'Farag, Elmoubasher', 'Coyle, Peter V.', 'Nader, Joanne Daghfal', 'Al-Khatib, Hebah A.', 'Elmagboul, Emad B.', 'Al Dhahry, Said', 'Al-Marri, Salih A.', 'Al Thani, Asmaa A.', 'Al Khal, Abdullatif', 'Al Maslamani, Muna A.', 'Yassine, Hadi M.']",PLoS One,,,True
7b54804f53035abb49bff572aec1c49fde636fe2,PMC,A qualitative descriptive study of the contextual factors influencing the practice of emergency nurses in managing emerging infectious diseases,http://dx.doi.org/10.1080/17482631.2019.1626179,PMC6566498,31184291,CC BY,"Purpose: Emergency nurses are engaged in the management of epidemic events that unfold along with the evolution of diseases. The goal of this study was to explore the contextual factors that inhibited the ability of emergency nurses to perform their duties in response to an outbreak. Methods: A qualitative descriptive design was used to explore the experiences and perceptions of emergency nurses. Participants were purposively recruited from 12 emergency departments in Hong Kong. Semi-structured face-to-face individual interviews were conducted with 26 emergency nurses. The audio-recorded interviews were transcribed verbatim and interpreted with a thematic analysis approach. Results: Four intertwined themes emerged from the analysis: resource constraints, threats of infection, ubiquitous changes and lingering uncertainties. These themes portrayed the constraints and challenges surrounding the work environment of emergency nurses. Conclusion: This study described the instabilities and vulnerabilities of the circumstances in which the emergency nurses were situated in during epidemic events. The findings shed light on the importance of hospitals and emergency departments in addressing both the technical problems and adaptive challenges that face emergency nurses during epidemic events.",2019 Jun 11,"['Lam, Stanley K. K.', 'Kwong, Enid W. Y.', 'Hung, Maria S. Y.', 'Pang, Samantha M. C.', 'Chien, Wai T.']",Int J Qual Stud Health Well-being,,,True
39063a51b2de47e1b2ef019d04eac54ca1c3f2d9,PMC,Health and zoonotic Infections of snow leopards Panthera unica in the South Gobi desert of Mongolia,http://dx.doi.org/10.1080/20008686.2019.1604063,PMC6567154,31231481,CC BY,"Background: Snow leopards, Panthera uncia, are a threatened apex predator, scattered across the mountains of Central and South Asia. Disease threats to wild snow leopards have not been investigated.Methods and Results: Between 2008 and 2015, twenty snow leopards in the South Gobi desert of Mongolia were captured and immobilised for health screening and radio-collaring. Blood samples and external parasites were collected for pathogen analyses using enzyme-linked immunosorbent assay (ELISA), microscopic agglutination test (MAT), and next-generation sequencing (NGS) techniques. The animals showed no clinical signs of disease, however, serum antibodies to significant zoonotic pathogens were detected. These pathogens included, Coxiella burnetii, (25% prevalence), Leptospira spp., (20%), and Toxoplasma gondii (20%). Ticks collected from snow leopards contained potentially zoonotic bacteria from the genera Bacillus, Bacteroides, Campylobacter, Coxiella, Rickettsia, Staphylococcus and Streptococcus.Conclusions: The zoonotic pathogens identified in this study, in the short-term did not appear to cause illness in the snow leopards, but have caused illness in other wild felids. Therefore, surveillance for pathogens should be implemented to monitor for potential longer- term disease impacts on this snow leopard population.",2019 Jun 5,"['Esson, Carol', 'Skerratt, Lee F.', 'Berger, Lee', 'Malmsten, Jonas', 'Strand, Tanja', 'Lundkvist, Åke', 'Järhult, Josef D.', 'Michaux, Johan', 'Mijiddorj, Tserennadmid Nadia', 'Bayrakçısmith, Rana', 'Mishra, Charudutt', 'Johansson, Örjan']",Infect Ecol Epidemiol,,,True
1adf578fb1c7019c2293b2e9c7cc3f036f9bc15b,PMC,Antibodies and vaccines against Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1080/22221751.2019.1624482,PMC6567157,31169078,CC BY,"The Middle East respiratory syndrome coronavirus (MERS-CoV) has spread through 27 countries and infected more than 2,200 people since its first outbreak in Saudi Arabia in 2012. The high fatality rate (35.4%) of this novel coronavirus and its persistent wide spread infectiousness in animal reservoirs have generated tremendous global public health concern. However, no licensed therapeutic agents or vaccines against MERS-CoV are currently available and only a limited few have entered clinical trials. Among all the potential targets of MERS-CoV, the spike glycoprotein (S) has been the most well-studied due to its critical role in mediating viral entry and in inducing a protective antibody response in infected individuals. The most notable studies include the recent discoveries of monoclonal antibodies and development of candidate vaccines against the S glycoprotein. Structural characterization of MERS-CoV S protein bound with these monoclonal antibodies has provided insights into the mechanisms of humoral immune responses against MERS-CoV infection. The current review aims to highlight these developments and discuss possible hurdles and strategies to translate these discoveries into ultimate medical interventions against MERS-CoV infection.",2019 Jun 6,"['Xu, Jiuyang', 'Jia, Wenxu', 'Wang, Pengfei', 'Zhang, Senyan', 'Shi, Xuanling', 'Wang, Xinquan', 'Zhang, Linqi']",Emerg Microbes Infect,,,True
db864a0b9b9bddd9b5ea861011655f363d90b149,PMC,Applications of Nanodiamonds in the Detection and Therapy of Infectious Diseases,http://dx.doi.org/10.3390/ma12101639,PMC6567273,31137476,CC BY,"We are constantly exposed to infectious diseases, and they cause millions of deaths per year. The World Health Organization (WHO) estimates that antibiotic resistance could cause 10 million deaths per year by 2050. Multidrug-resistant bacteria are the cause of infection in at least one in three people suffering from septicemia. While antibiotics are powerful agents against infectious diseases, the alarming increase in antibiotic resistance is of great concern. Alternatives are desperately needed, and nanotechnology provides a great opportunity to develop novel approaches for the treatment of infectious diseases. One of the most important factors in the prognosis of an infection caused by an antibiotic resistant bacteria is an early and rigorous diagnosis, jointly with the use of novel therapeutic systems that can specifically target the pathogen and limit the selection of resistant strains. Nanodiamonds can be used as antimicrobial agents due to some of their properties including size, shape, and biocompatibility, which make them highly suitable for the development of efficient and tailored nanotherapies, including vaccines or drug delivery systems. In this review, we discuss the beneficial findings made in the nanodiamonds field, focusing on diagnosis and treatment of infectious diseases. We also highlight the innovative platform that nanodiamonds confer for vaccine improvement, drug delivery, and shuttle systems, as well as their role in the generation of faster and more sensitive clinical diagnosis.",2019 May 20,"['Torres Sangiao, Eva', 'Holban, Alina Maria', 'Gestal, Mónica Cartelle']",Materials (Basel),,,True
e0e0a545d003e79b46773517d09ac3e7af93ba3f,PMC,"Human adenovirus among hospitalized children with respiratory tract infections in Beijing, China, 2017–2018",http://dx.doi.org/10.1186/s12985-019-1185-x,PMC6567909,31196108,CC BY,"BACKGROUND: Human adenoviruses (HAdVs) cause a wide range of diseases. However, the genotype diversity and epidemiological information relating to HAdVs among hospitalized children with respiratory tract infections (RTIs) is limited. Here, we describe the epidemiology and genotype distribution of HAdVs associated with RTIs in Beijing, China. METHODS: Nasopharyngeal aspirates (NPA) were collected from hospitalized children with RTIs from April 2017 to March 2018. HAdVs were detected by a TaqMan-based quantitative real-time polymerase chain reaction (qPCR) assay, and the hexon gene was used for phylogenetic analysis. Epidemiological data were analyzed using statistical product and service solutions (SPSS) 21.0 software. RESULTS: HAdV was detected in 72 (5.64%) of the 1276 NPA specimens, with most (86.11%, 62/72) HAdV-positives cases detected among children < 6 years of age. HAdV-B3 (56.06%, 37/66) and HAdV-C2 (19.70%, 13/66) were the most frequent. Of the 72 HAdV-infected cases, 27 (37.50%) were co-infected with other respiratory viruses, most commonly parainfluenza virus (12.50%, 9/72) and rhinovirus (9.72%, 7/72). The log number of viral load ranged from 3.30 to 9.14 copies per mL of NPA, with no significant difference between the HAdV mono- and co-infection groups. The main clinical symptoms in the HAdV-infected patients were fever and cough, and 62 (86.11%, 62/72) were diagnosed with pneumonia. Additionally, HAdVs were detected throughout the year with a higher prevalence in summer. CONCLUSIONS: HAdV prevalence is related to age and season. HAdV-B and HAdV-C circulated simultaneously among the hospitalized children with RTIs in Beijing, and HAdV-B type 3 and HAdV-C type 2 were the most frequent.",2019 Jun 13,"['Yao, Li-hong', 'Wang, Chao', 'Wei, Tian-li', 'Wang, Hao', 'Ma, Fen-lian', 'Zheng, Li-shu']",Virol J,,,True
1b64709bd4f9ba56a4209bd32c07a89d1beec6c7,PMC,"Health system capacity in Sydney, Australia in the event of a biological attack with smallpox",http://dx.doi.org/10.1371/journal.pone.0217704,PMC6568391,31199825,CC BY,"Planning for a re-emergent epidemic of smallpox requires surge capacity of space, resources and personnel within health systems. There are many uncertainties in such a scenario, including likelihood and size of an attack, speed of response and health system capacity. We used a model for smallpox transmission to determine requirements for hospital beds, contact tracing and health workers (HCWs) in Sydney, Australia, during a modelled epidemic of smallpox. Sensitivity analysis was done on attack size, speed of response and proportion of case isolation and contact tracing. We estimated 100638 clinical HCWs and 14595 public hospital beds in Sydney. Rapid response, case isolation and contact tracing are influential on epidemic size, with case isolation more influential than contact tracing. With 95% of cases isolated, outbreak control can be achieved within 100 days even with only 50% of contacts traced. However, if case isolation and contact tracing both fall to 50%, epidemic control is lost. With a smaller initial attack and a response commencing 20 days after the attack, health system impacts are modest. The requirement for hospital beds will vary from up to 4% to 100% of all available beds in best and worst case scenarios. If the response is delayed, or if the attack infects 10000 people, all available beds will be exceeded within 40 days, with corresponding surge requirements for clinical health care workers (HCWs). We estimated there are 330 public health workers in Sydney with up to 940,350 contacts to be traced. At least 3 million respirators will be needed for the first 100 days. To ensure adequate health system capacity, rapid response, high rates of case isolation, excellent contact tracing and vaccination, and protection of HCWs should be a priority. Surge capacity must be planned. Failures in any of these could cause health system failure, with inadequate beds, quarantine spaces, personnel, PPE and inability to manage other acute health conditions.",2019 Jun 14,"['MacIntyre, Chandini Raina', 'Costantino, Valentina', 'Kunasekaran, Mohana Priya']",PLoS One,,,True
9c1b3d1c613332e439a3a925588b2ee3b9bcf18e,PMC,Protein quality control in the nucleolus safeguards recovery of epigenetic regulators after heat shock,http://dx.doi.org/10.7554/eLife.45205,PMC6570483,31199242,CC BY,"Maintenance of epigenetic modifiers is of utmost importance to preserve the epigenome and consequently appropriate cellular functioning. Here, we analyzed Polycomb group protein (PcG) complex integrity in response to heat shock (HS). Upon HS, various Polycomb Repressive Complex (PRC)1 and PRC2 subunits, including CBX proteins, but also other chromatin regulators, are found to accumulate in the nucleolus. In parallel, binding of PRC1/2 to target genes is strongly reduced, coinciding with a dramatic loss of H2AK119ub and H3K27me3 marks. Nucleolar-accumulated CBX proteins are immobile, but remarkably both CBX protein accumulation and loss of PRC1/2 epigenetic marks are reversible. This post-heat shock recovery of pan-nuclear CBX protein localization and reinstallation of epigenetic marks is HSP70 dependent. Our findings demonstrate that the nucleolus is an essential protein quality control center, which is indispensable for recovery of epigenetic regulators and maintenance of the epigenome after heat shock.",,"['Azkanaz, Maria', 'Rodríguez López, Aida', 'de Boer, Bauke', 'Huiting, Wouter', 'Angrand, Pierre-Olivier', 'Vellenga, Edo', 'Kampinga, Harm H', 'Bergink, Steven', 'Martens, Joost HA', 'Schuringa, Jan Jacob', 'van den Boom, Vincent']",eLife.; 8:e45205,,,True
dcfbf04c5bf819de0d261d15a1936288f578d416,PMC,Ambulatory and stationary healthcare use in survivors of ARDS during the first year after discharge from ICU: findings from the DACAPO cohort,http://dx.doi.org/10.1186/s13613-019-0544-5,PMC6570725,31201576,CC BY,"BACKGROUND: For many survivors of acute respiratory distress syndrome (ARDS), the process from discharge from intensive care unit (ICU) to recovery is long and difficult. However, healthcare use after discharge from ICU has received only little attention by research. This study sets out to investigate the extent of ambulatory and stationary healthcare use among survivors of ARDS in Germany (multicenter DACAPO cohort) and to analyze predictors of stationary healthcare use. RESULTS: A total of 396 survivors of ARDS provided data at 1 year after discharge from ICU. Fifty percent of 1-year survivors were hospitalized for 48 days or longer after discharge from ICU, with 10% spending more than six out of 12 months in stationary care. The duration of hospitalization increased significantly by the length of the initial ICU stay. All participants reported at least one outpatient visit (including visits to general practitioners), and 50% contacted four or more different medical specialties within the first year after discharge from ICU. CONCLUSIONS: For most of the patients, the first year after ARDS is characterized by an extensive amount of healthcare utilization, especially with regard to stationary health care. These findings shed light on the substantial morbidity of patients after ARDS and contribute to a better understanding of the situation of patients following discharge from ICU.",2019 Jun 14,"['Brandstetter, Susanne', 'Dodoo-Schittko, Frank', 'Brandl, Magdalena', 'Blecha, Sebastian', 'Bein, Thomas', 'Apfelbacher, Christian', None]",Ann Intensive Care,,,True
89d98e705490a5ab2eb7fd40de4541bba9051abb,PMC,HIV Vaccine Mystery and Viral Shell Disorder,http://dx.doi.org/10.3390/biom9050178,PMC6572542,31072073,CC BY,"Hundreds of billions of dollars have been spent for over three decades in the search for an effective human immunodeficiency virus (HIV) vaccine with no success. There are also at least two other sexually transmitted viruses, for which no vaccine is available, the herpes simplex virus (HSV) and the hepatitis C virus (HCV). Traditional textbook explanatory paradigm of rapid mutation of retroviruses cannot adequately address the unavailability of vaccine for many sexually transmissible viruses, since HSV and HCV are DNA and non-retroviral RNA viruses, respectively, whereas effective vaccine for the horsefly-transmitted retroviral cousin of HIV, equine infectious anemia virus (EIAV), was found in 1973. We reported earlier the highly disordered nature of proteins in outer shells of the HIV, HCV, and HSV. Such levels of disorder are completely absent among the classical viruses, such as smallpox, rabies, yellow fever, and polio viruses, for which efficient vaccines were discovered. This review analyzes the physiology and shell disorder of the various related and non-related viruses to argue that EIAV and the classical viruses need harder shells to survive during harsher conditions of non-sexual transmissions, thus making them vulnerable to antibody detection and neutralization. In contrast, the outer shell of the HIV-1 (with its preferential sexual transmission) is highly disordered, thereby allowing large scale motions of its surface glycoproteins and making it difficult for antibodies to bind to them. The theoretical underpinning of this concept is retrospectively traced to a classical 1920s experiment by the legendary scientist, Oswald Avery. This concept of viral shapeshifting has implications for improved treatment of cancer and infections via immune evasion.",2019 May 8,"['Goh, Gerard Kian-Meng', 'Dunker, A. Keith', 'Foster, James A.', 'Uversky, Vladimir N.']",Biomolecules,,,True
d880151d3c6128788253389d87094b7cc1154837,PMC,"epicontacts: Handling, visualisation and analysis of epidemiological contacts",http://dx.doi.org/10.12688/f1000research.14492.2,PMC6572866,31240097,CC BY,"Epidemiological outbreak data is often captured in line list and contact format to facilitate contact tracing for outbreak control. epicontacts is an R package that provides a unique data structure for combining these data into a single object in order to facilitate more efficient visualisation and analysis. The package incorporates interactive visualisation functionality as well as network analysis techniques. Originally developed as part of the Hackout3 event, it is now developed, maintained and featured as part of the R Epidemics Consortium (RECON). The package is available for download from the Comprehensive R Archive Network (CRAN) and GitHub.",2018 Oct 11,"['Nagraj, VP', 'Randhawa, Nistara', 'Campbell, Finlay', 'Crellen, Thomas', 'Sudre, Bertrand', 'Jombart, Thibaut']",F1000Res,,,True
f64d07df542245c19781c36476a6cde273627f87,PMC,Drug Repurposing to Fight Colistin and Carbapenem-Resistant Bacteria,http://dx.doi.org/10.3389/fcimb.2019.00193,PMC6579884,31245302,CC BY,"The emergence of new resistance mechanisms, the failure of classical antibiotics in clinic, the decrease in the development of antibiotics in the industry are all challenges that lead us to consider new strategies for the treatment of infectious diseases. Indeed, in recent years controversy has intensified over strains resistant to carbapenem and/or colistin. Various therapeutic solutions are used to overcome administration of last line antibiotics. In this context, drug repurposing, which consists of using a non-antibiotic compound to treat multi-drug resistant bacteria (MDR), is encouraged. In this review, we first report what may have led to drug repurposing. Main definitions, advantages and drawbacks are summarized. Three major methods are described: phenotypic, computational and serendipity. In a second time we will focus on the current knowledge in drug repurposing for carbapenem and colistin-resistant bacteria with different studies describing repurposed compounds tested on Gram-negative bacteria. Furthermore, we show that drug combination therapies can increase successful by drug repurposing strategy. In conclusion, we discuss the pharmaceutical industries that have little interest in reprofiling drugs due to lack of profits. We also consider what a clinician might think of the indications of these uncommon biologists to treat MDR bacterial infections and avoid therapeutic impasses.",2019 Jun 11,"['Peyclit, Lucie', 'Baron, Sophie Alexandra', 'Rolain, Jean-Marc']",Front Cell Infect Microbiol,,,True
f849d3e71f4d2eae8a1e39802195bc9c06fc30ae,PMC,Respiratory virus associated with surgery in children patients,http://dx.doi.org/10.1186/s12931-019-1086-y,PMC6580463,31208426,CC BY,"BACKGROUND: Viral respiratory infection (VRI) is a common contraindication to elective surgery. Asymptomatic shedding among pediatric surgery patients (PSPs) could potentially lead to progression of symptomatic diseases and cause outbreaks of respiratory diseases. The aim of this study is to investigate the incidence of infection among mild symptomatic PSP group and asymptomatic PSP group after surgical procedure. METHODS: We collected the induced sputum from enrolled 1629 children (under 18 years of age) with no respiratory symptom prior to pediatric surgery between March 2017 and February 2019. We tested 16 different respiratory virus infections in post-surgery mild symptomatic PSP group and asymptomatic PSP group using a quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) assay panel. We analyzed symptom data and quantitative viral load to investigate the association between viruses, symptoms and viral quantity in qRT-PCR-positive PSPs. RESULTS: Out of 1629 children enrolled, a total of 204 respiratory viruses were present in 171 (10.50%) PSPs including 47 patients with mild symptoms and 124 with no symptoms after surgery. Commonly detected viruses were human rhino/enterovirus (HRV/EV, 42.19%), parainfluenza virus 3 (PIV3, 24.48%), coronavirus (CoV NL63, OC43, HKU1, 11.46%), and respiratory syncytial virus (RSV, 9.9%). PIV3 infection with a higher viral load was frequently found in PSPs presenting with mild symptoms, progressing to pneumonia with radiographic evidence after surgery. HRV/EV were the most commonly detected pathogens in both asymptomatic and mild symptomatic PSPs. CoV (OC43, HKU1) infections with a higher viral load were mostly observed in asymptomatic PSPs progressing to alveolar or interstitial infiltration. CONCLUSIONS: Our study suggested that PIV3 is a new risk factor for VRI in PSPs. Employing a more comprehensive, sensitive and quantitative method should be considered for preoperative testing of respiratory viruses in order to guide optimal surgical timing.",2019 Jun 17,"['Zhang, Dan', 'Lou, Xiuyu', 'Yan, Hao', 'Pan, Junhang', 'Mao, Haiyan', 'Tang, Hongfeng', 'Shu, Yan', 'Zhao, Yun', 'Liu, Lei', 'Li, Junping', 'Chen, Dong', 'Zhang, Yanjun', 'Ma, Xuejun']",Respir Res,,,True
6276adaeca8fcd42c9565718ac6bbdc4f97aa10f,PMC,A single-dose ChAdOx1-vectored vaccine provides complete protection against Nipah Bangladesh and Malaysia in Syrian golden hamsters,http://dx.doi.org/10.1371/journal.pntd.0007462,PMC6581282,31170144,CC0,"Nipah virus (NiV) is a highly pathogenic re-emerging virus that causes outbreaks in South East Asia. Currently, no approved and licensed vaccine or antivirals exist. Here, we investigated the efficacy of ChAdOx1 NiV(B), a simian adenovirus-based vaccine encoding NiV glycoprotein (G) Bangladesh, in Syrian hamsters. Prime-only as well as prime-boost vaccination resulted in uniform protection against a lethal challenge with NiV Bangladesh: all animals survived challenge and we were unable to find infectious virus either in oral swabs, lung or brain tissue. Furthermore, no pathological lung damage was observed. A single-dose of ChAdOx1 NiV(B) also prevented disease and lethality from heterologous challenge with NiV Malaysia. While we were unable to detect infectious virus in swabs or tissue of animals challenged with the heterologous strain, a very limited amount of viral RNA could be found in lung tissue by in situ hybridization. A single dose of ChAdOx1 NiV(B) also provided partial protection against Hendra virus and passive transfer of antibodies elicited by ChAdOx1 NiV(B) vaccination partially protected Syrian hamsters against NiV Bangladesh. From these data, we conclude that ChAdOx1 NiV(B) is a suitable candidate for further NiV vaccine pre-clinical development.",2019 Jun 6,"['van Doremalen, Neeltje', 'Lambe, Teresa', 'Sebastian, Sarah', 'Bushmaker, Trenton', 'Fischer, Robert', 'Feldmann, Friederike', 'Haddock, Elaine', 'Letko, Michael', 'Avanzato, Victoria A.', 'Rissanen, Ilona', 'LaCasse, Rachel', 'Scott, Dana', 'Bowden, Thomas A.', 'Gilbert, Sarah', 'Munster, Vincent']",PLoS Negl Trop Dis,,,True
3393483e94f1917cbfd9cb9c3cb3f4bb5ef9eeaa,PMC,Neutralization of Acidic Intracellular Vesicles by Niclosamide Inhibits Multiple Steps of the Dengue Virus Life Cycle In Vitro,http://dx.doi.org/10.1038/s41598-019-45095-1,PMC6582152,31213630,CC BY,"Dengue fever is one of the most important mosquito-borne viral infections in large parts of tropical and subtropical countries and is a significant public health concern and socioeconomic burden. There is an urgent need to develop antivirals that can effectively reduce dengue virus (DENV) replication and decrease viral load. Niclosamide, an antiparasitic drug approved for human use, has been recently identified as an effective antiviral agent against a number of pH-dependent viruses, including flaviviruses. Here, we reveal that neutralization of low-pH intracellular compartments by niclosamide affects multiple steps of the DENV infectious cycle. Specifically, niclosamide-induced endosomal neutralization not only prevents viral RNA replication but also affects the maturation of DENV particles, rendering them non-infectious. We found that niclosamide-induced endosomal neutralization prevented E glycoprotein conformational changes on the virion surface of flaviviruses, resulting in the release of non-infectious immature virus particles with uncleaved pr peptide from host cells. Collectively, our findings support the potential application of niclosamide as an antiviral agent against flavivirus infection and highlight a previously uncharacterized mechanism of action of the drug.",2019 Jun 18,"['Jung, Eunhye', 'Nam, Sangwoo', 'Oh, Hyeryeon', 'Jun, Sangmi', 'Ro, Hyun-Joo', 'Kim, Baek', 'Kim, Meehyein', 'Go, Yun Young']",Sci Rep,,,False
61722c462b054f36461375e96e502cbf22648c04,PMC,Neutralization of Acidic Intracellular Vesicles by Niclosamide Inhibits Multiple Steps of the Dengue Virus Life Cycle In Vitro,http://dx.doi.org/10.1038/s41598-019-45095-1,PMC6582152,31213630,CC BY,"Dengue fever is one of the most important mosquito-borne viral infections in large parts of tropical and subtropical countries and is a significant public health concern and socioeconomic burden. There is an urgent need to develop antivirals that can effectively reduce dengue virus (DENV) replication and decrease viral load. Niclosamide, an antiparasitic drug approved for human use, has been recently identified as an effective antiviral agent against a number of pH-dependent viruses, including flaviviruses. Here, we reveal that neutralization of low-pH intracellular compartments by niclosamide affects multiple steps of the DENV infectious cycle. Specifically, niclosamide-induced endosomal neutralization not only prevents viral RNA replication but also affects the maturation of DENV particles, rendering them non-infectious. We found that niclosamide-induced endosomal neutralization prevented E glycoprotein conformational changes on the virion surface of flaviviruses, resulting in the release of non-infectious immature virus particles with uncleaved pr peptide from host cells. Collectively, our findings support the potential application of niclosamide as an antiviral agent against flavivirus infection and highlight a previously uncharacterized mechanism of action of the drug.",2019 Jun 18,"['Jung, Eunhye', 'Nam, Sangwoo', 'Oh, Hyeryeon', 'Jun, Sangmi', 'Ro, Hyun-Joo', 'Kim, Baek', 'Kim, Meehyein', 'Go, Yun Young']",Sci Rep,,,True
74a81638dc54bc8e0fee501f23723bda2761195b,PMC,Reversible ADP-ribosylation of RNA,http://dx.doi.org/10.1093/nar/gkz305,PMC6582358,31216043,CC BY,"ADP-ribosylation is a reversible chemical modification catalysed by ADP-ribosyltransferases such as PARPs that utilize nicotinamide adenine dinucleotide (NAD(+)) as a cofactor to transfer monomer or polymers of ADP-ribose nucleotide onto macromolecular targets such as proteins and DNA. ADP-ribosylation plays an important role in several biological processes such as DNA repair, transcription, chromatin remodelling, host-virus interactions, cellular stress response and many more. Using biochemical methods we identify RNA as a novel target of reversible mono-ADP-ribosylation. We demonstrate that the human PARPs - PARP10, PARP11 and PARP15 as well as a highly diverged PARP homologue TRPT1, ADP-ribosylate phosphorylated ends of RNA. We further reveal that ADP-ribosylation of RNA mediated by PARP10 and TRPT1 can be efficiently reversed by several cellular ADP-ribosylhydrolases (PARG, TARG1, MACROD1, MACROD2 and ARH3), as well as by MACROD-like hydrolases from VEEV and SARS viruses. Finally, we show that TRPT1 and MACROD homologues in bacteria possess activities equivalent to the human proteins. Our data suggest that RNA ADP-ribosylation may represent a widespread and physiologically relevant form of reversible ADP-ribosylation signalling.",2019 Jun 20,"['Munnur, Deeksha', 'Bartlett, Edward', 'Mikolčević, Petra', 'Kirby, Ilsa T', 'Matthias\xa0Rack, Johannes Gregor', 'Mikoč, Andreja', 'Cohen, Michael S', 'Ahel, Ivan']",Nucleic Acids Res,,,True
30353e453a555d5beaaf27afcb4280edad774d7d,PMC,Reversible ADP-ribosylation of RNA,http://dx.doi.org/10.1093/nar/gkz305,PMC6582358,31216043,CC BY,"ADP-ribosylation is a reversible chemical modification catalysed by ADP-ribosyltransferases such as PARPs that utilize nicotinamide adenine dinucleotide (NAD(+)) as a cofactor to transfer monomer or polymers of ADP-ribose nucleotide onto macromolecular targets such as proteins and DNA. ADP-ribosylation plays an important role in several biological processes such as DNA repair, transcription, chromatin remodelling, host-virus interactions, cellular stress response and many more. Using biochemical methods we identify RNA as a novel target of reversible mono-ADP-ribosylation. We demonstrate that the human PARPs - PARP10, PARP11 and PARP15 as well as a highly diverged PARP homologue TRPT1, ADP-ribosylate phosphorylated ends of RNA. We further reveal that ADP-ribosylation of RNA mediated by PARP10 and TRPT1 can be efficiently reversed by several cellular ADP-ribosylhydrolases (PARG, TARG1, MACROD1, MACROD2 and ARH3), as well as by MACROD-like hydrolases from VEEV and SARS viruses. Finally, we show that TRPT1 and MACROD homologues in bacteria possess activities equivalent to the human proteins. Our data suggest that RNA ADP-ribosylation may represent a widespread and physiologically relevant form of reversible ADP-ribosylation signalling.",2019 Jun 20,"['Munnur, Deeksha', 'Bartlett, Edward', 'Mikolčević, Petra', 'Kirby, Ilsa T', 'Matthias\xa0Rack, Johannes Gregor', 'Mikoč, Andreja', 'Cohen, Michael S', 'Ahel, Ivan']",Nucleic Acids Res,,,False
57ae4e660730c4f3591f27a4058164362d6f5cb4,PMC,Recent advances on the role of host factors during non-poliovirus enteroviral infections,http://dx.doi.org/10.1186/s12929-019-0540-y,PMC6582496,31215493,CC BY,"Non-polio enteroviruses are emerging viruses known to cause outbreaks of polio-like infections in different parts of the world with several cases already reported in Asia Pacific, Europe and in United States of America. These outbreaks normally result in overstretching of health facilities as well as death in children under the age of five. Most of these infections are usually self-limiting except for the neurological complications associated with human enterovirus A 71 (EV-A71). The infection dynamics of these viruses have not been fully understood, with most inferences made from previous studies conducted with poliovirus. Non-poliovirus enteroviral infections are responsible for major outbreaks of hand, foot and mouth disease (HFMD) often associated with neurological complications and severe respiratory diseases. The myriad of disease presentations observed so far in children calls for an urgent need to fully elucidate the replication processes of these viruses. There are concerted efforts from different research groups to fully map out the role of human host factors in the replication cycle of these viral infections. Understanding the interaction between viral proteins and human host factors will unravel important insights on the lifecycle of this groups of viruses. This review provides the latest update on the interplay between human host factors/processes and non-polio enteroviruses (NPEV). We focus on the interactions involved in viral attachment, entry, internalization, uncoating, replication, virion assembly and eventual egress of the NPEV from the infected cells. We emphasize on the virus- human host interplay and highlight existing knowledge gaps that needs further studies. Understanding the NPEV-human host factors interactions will be key in the design and development of vaccines as well as antivirals against enteroviral infections. Dissecting the role of human host factors during NPEV infection cycle will provide a clear picture of how NPEVs usurp the human cellular processes to establish an efficient infection. This will be a boost to the drug and vaccine development against enteroviruses which will be key in control and eventual elimination of the viral infections.",2019 Jun 19,"['Owino, Collins Oduor', 'Chu, Justin Jang Hann']",J Biomed Sci,,,True
b66c037ebfee8059dd47d2614cf5d55618d8260f,PMC,Junín virus induces autophagy in human A549 cells,http://dx.doi.org/10.1371/journal.pone.0218730,PMC6583977,31216340,CC BY,"Autophagy, a highly regulated degradative process that promotes cellular homeostasis, is increasingly recognised as a fundamental component of the cellular response against viral infection. In this study, we investigated the role of autophagy during Junín virus (JUNV) multiplication using human A549 cells. We found that JUNV infection induces an increment of the LC3-II/LC3-I ratio, an accumulation of punctate pattern in RFP-LC3-transfected cells and the colocalisation of viral nucleoprotein and LC3 protein, suggesting autophagosome formation. JUNV infection also induced the degradation of the autophagy receptor p62, suggesting that complete autophagic flux was triggered. In addition, we showed that inhibition of autophagy with bafilomycin A1 or 3-methyladenine significantly reduces viral multiplication. Moreover, viral yield was increased when autophagy was induced using rapamycin. Furthermore, JUNV infection induced the colocalisation of p62, ATG16, RAB5, RAB7A and LAMP1 with the autophagosomal LC3 protein. That suggests that phagosomes undergo the maturation process during viral infection. Finally, we demonstrated that siRNA experiments targeting essential autophagy genes (ATG5, ATG7 and Beclin 1) reduce viral protein synthesis and viral yield. Overall, our results indicate that JUNV activates host autophagy machinery enhancing its multiplication.",2019 Jun 19,"['Perez Vidakovics, Maria Laura A.', 'Ure, Agustín E.', 'Arrías, Paula N.', 'Romanowski, Víctor', 'Gómez, Ricardo M.']",PLoS One,,,True
2a8c19fd53b06d204166b36d745eba911bfdefbc,PMC,Complementing conventional infectious disease surveillance with national health insurance claims data in the Republic of Korea,http://dx.doi.org/10.1038/s41598-019-45409-3,PMC6584579,31217476,CC BY,"Surveillance remains an important tool for timely outbreak detection and response. Many countries, including Korea, have established national infectious disease surveillance systems with clinical notification. We aimed to evaluate the National Health Insurance Claims-based Surveillance (NHICS) compared to conventional passive report-based National Infectious Diseases Surveillance (NIDS). Reported to claimed cases ratios (R/C ratio) were evaluated from monthly notifiable disease cases captured by NIDS and NHICS. The relationships between 26 infectious diseases and each surveillance system were analysed using Pearson’s correlation analysis and linear regression. There was an overall increase in R/C ratio from 2010–2017 (0.37 to 0.78). In 22 infectious diseases, there was a correlation between NIDS and NHICS. Moreover, claim-based surveillance showed less fluctuating disease incidence rates than report-based surveillance for specific infectious diseases, such as varicella, mumps, and scarlet fever. However, for infectious diseases with episodic outbreaks or low incidence, it was difficult to assess NHICS usefulness. Claim-based surveillance is less affected by limitations of conventional report-based surveillance systems, such as reporting rate. Given delays in claim systems, a claim-based surveillance is expected to be complementary to conventional systems for the detection of various infectious diseases with the advancement of bio-information technology.",2019 Jun 19,"['Jung, Jaehun', 'Im, Jae Hyoung', 'Ko, Young-Jin', 'Huh, Kyungmin', 'Yoon, Chang-gyo', 'Rhee, Chulwoo', 'Kim, Young-Eun', 'Go, Dun-Sol', 'Kim, Arim', 'Jung, Yunsun', 'Radnaabaatar, Munkhzul', 'Yoon, Seok-Jun']",Sci Rep,,,False
1843389daffca2a8b5e04048821ce881eb068269,PMC,Complementing conventional infectious disease surveillance with national health insurance claims data in the Republic of Korea,http://dx.doi.org/10.1038/s41598-019-45409-3,PMC6584579,31217476,CC BY,"Surveillance remains an important tool for timely outbreak detection and response. Many countries, including Korea, have established national infectious disease surveillance systems with clinical notification. We aimed to evaluate the National Health Insurance Claims-based Surveillance (NHICS) compared to conventional passive report-based National Infectious Diseases Surveillance (NIDS). Reported to claimed cases ratios (R/C ratio) were evaluated from monthly notifiable disease cases captured by NIDS and NHICS. The relationships between 26 infectious diseases and each surveillance system were analysed using Pearson’s correlation analysis and linear regression. There was an overall increase in R/C ratio from 2010–2017 (0.37 to 0.78). In 22 infectious diseases, there was a correlation between NIDS and NHICS. Moreover, claim-based surveillance showed less fluctuating disease incidence rates than report-based surveillance for specific infectious diseases, such as varicella, mumps, and scarlet fever. However, for infectious diseases with episodic outbreaks or low incidence, it was difficult to assess NHICS usefulness. Claim-based surveillance is less affected by limitations of conventional report-based surveillance systems, such as reporting rate. Given delays in claim systems, a claim-based surveillance is expected to be complementary to conventional systems for the detection of various infectious diseases with the advancement of bio-information technology.",2019 Jun 19,"['Jung, Jaehun', 'Im, Jae Hyoung', 'Ko, Young-Jin', 'Huh, Kyungmin', 'Yoon, Chang-gyo', 'Rhee, Chulwoo', 'Kim, Young-Eun', 'Go, Dun-Sol', 'Kim, Arim', 'Jung, Yunsun', 'Radnaabaatar, Munkhzul', 'Yoon, Seok-Jun']",Sci Rep,,,True
dc26c72d4373332c80c9cab18a7e3a8b41211333,PMC,Microbial Proteases Applications,http://dx.doi.org/10.3389/fbioe.2019.00110,PMC6584820,31263696,CC BY,"The use of chemicals around the globe in different industries has increased tremendously, affecting the health of people. The modern world intends to replace these noxious chemicals with environmental friendly products for the betterment of life on the planet. Establishing enzymatic processes in spite of chemical processes has been a prime objective of scientists. Various enzymes, specifically microbial proteases, are the most essentially used in different corporate sectors, such as textile, detergent, leather, feed, waste, and others. Proteases with respect to physiological and commercial roles hold a pivotal position. As they are performing synthetic and degradative functions, proteases are found ubiquitously, such as in plants, animals, and microbes. Among different producers of proteases, Bacillus sp. are mostly commercially exploited microbes for proteases. Proteases are successfully considered as an alternative to chemicals and an eco-friendly indicator for nature or the surroundings. The evolutionary relationship among acidic, neutral, and alkaline proteases has been analyzed based on their protein sequences, but there remains a lack of information that regulates the diversity in their specificity. Researchers are looking for microbial proteases as they can tolerate harsh conditions, ways to prevent autoproteolytic activity, stability in optimum pH, and substrate specificity. The current review focuses on the comparison among different proteases and the current problems faced during production and application at the industrial level. Deciphering these issues would enable us to promote microbial proteases economically and commercially around the world.",2019 Jun 12,"['Razzaq, Abdul', 'Shamsi, Sadia', 'Ali, Arfan', 'Ali, Qurban', 'Sajjad, Muhammad', 'Malik, Arif', 'Ashraf, Muhammad']",Front Bioeng Biotechnol,,,True
a95e3a09d229a35ff2189682c618cff5add85e4a,PMC,Research in epidemic and emergency situations: A model for collaboration and expediting ethics review in two Caribbean countries,http://dx.doi.org/10.1111/dewb.12157,PMC6586066,28752914,CC BY,"Various forms of research are essential in emergency, disaster and disease outbreak situations, but challenges exist including the long length of time it takes to get research proposals approved. Consequently, it would be very advantageous to have an acceptable model for efficient coordination and communication between and among research ethics committees/IRBs and ministries of health, and templates for expediting (done with speed and efficiency) ethical review of research proposals in emergency and epidemic situations to be used across the Caribbean and in other low and middle income countries. This project involved a literature search and the interviewing of ministry of health officials, public health practitioners, and research ethics committee/IRB members in Jamaica and St. Lucia, to obtain suggestions for the best model for efficient coordination and communication between research ethics committees (RECs), and developed a template for expediting review of research protocols in epidemic and emergency conditions.",2018 Dec 28,"Aarons, Derrick",Dev World Bioeth,,,True
9c135ad34ff29dfceef573e3fd18be8b3599ac72,PMC,Noninvasive ventilation in critically ill patients with the Middle East respiratory syndrome,http://dx.doi.org/10.1111/irv.12635,PMC6586182,30884185,CC BY,"BACKGROUND: Noninvasive ventilation (NIV) has been used in patients with the Middle East respiratory syndrome (MERS) with acute hypoxemic respiratory failure, but the effectiveness of this approach has not been studied. METHODS: Patients with MERS from 14 Saudi Arabian centers were included in this analysis. Patients who were initially managed with NIV were compared to patients who were managed only with invasive mechanical ventilation (invasive MV). RESULTS: Of 302 MERS critically ill patients, NIV was used initially in 105 (35%) patients, whereas 197 (65%) patients were only managed with invasive MV. Patients who were managed with NIV initially had lower baseline SOFA score and less extensive infiltrates on chest radiograph compared with patients managed with invasive MV. The vast majority (92.4%) of patients who were managed initially with NIV required intubation and invasive mechanical ventilation, and were more likely to require inhaled nitric oxide compared to those who were managed initially with invasive MV. ICU and hospital length of stay were similar between NIV patients and invasive MV patients. The use of NIV was not independently associated with 90‐day mortality (propensity score‐adjusted odds ratio 0.61, 95% CI [0.23, 1.60] P = 0.27). CONCLUSIONS: In patients with MERS and acute hypoxemic respiratory failure, NIV failure was very high. The use of NIV was not associated with improved outcomes.",2019 Jul 18,"['Alraddadi, Basem M.', 'Qushmaq, Ismael', 'Al‐Hameed, Fahad M.', 'Mandourah, Yasser', 'Almekhlafi, Ghaleb A.', 'Jose, Jesna', 'Al‐Omari, Awad', 'Kharaba, Ayman', 'Almotairi, Abdullah', 'Al Khatib, Kasim', 'Shalhoub, Sarah', 'Abdulmomen, Ahmed', 'Mady, Ahmed', 'Solaiman, Othman', 'Al‐Aithan, Abdulsalam M.', 'Al‐Raddadi, Rajaa', 'Ragab, Ahmed', 'Balkhy, Hanan H.', 'Al Harthy, Abdulrahman', 'Sadat, Musharaf', 'Tlayjeh, Haytham', 'Merson, Laura', 'Hayden, Frederick G.', 'Fowler, Robert A.', 'Arabi, Yaseen M.', None]",Influenza Other Respir Viruses,,,True
6493fb02dfb851e5f1ca0d5f196b381a67dba56d,PMC,"Feasibility study for the use of self‐collected nasal swabs to identify pathogens among participants of a population‐based surveillance system for acute respiratory infections (GrippeWeb‐Plus)—Germany, 2016",http://dx.doi.org/10.1111/irv.12644,PMC6586186,30925029,CC BY,"BACKGROUND: Internet‐based participatory surveillance systems, such as the German GrippeWeb, monitor the frequency of acute respiratory illnesses on population level. In order to interpret syndromic information better, we devised a microbiological feasibility study (GrippeWeb‐Plus) to test whether self‐collection of anterior nasal swabs is operationally possible, acceptable for participants and can yield valid data. METHODS: We recruited 103 GrippeWeb participants (73 adults and 30 children) and provided them with a kit, instructions and a questionnaire for each sample. In the first half of 2016, participants took an anterior nasal swab and sent it to the Robert Koch Institute whenever an acute respiratory illness occurred. Reporting of illnesses through the GrippeWeb platform continued as usual. We analysed swabs for the presence of human c‐myc‐DNA and 22 viral and bacterial pathogens. After the study, we sent participants an evaluation questionnaire. We analysed timeliness, completeness, acceptability and validity. RESULTS: One hundred and two participants submitted 225 analysable swabs. Ninety per cent of swabs were taken within 3 days of symptom onset. Eighty‐nine per cent of swabs had a corresponding reported illness in the GrippeWeb system. Ninety‐nine per cent of adults and 96% of children would be willing to participate in a self‐swabbing scheme for a longer period. All swabs contained c‐myc‐DNA. In 119 swabs, we identified any of 14 viruses but no bacteria. The positivity rate of influenza was similar to that in the German physician sentinel. CONCLUSION: Self‐collection of anterior nasal swabs proofed to be feasible, was well accepted by participants, gave valid results and was an informative adjunct to syndromic data.",2019 Jul 29,"['Haussig, Joana M.', 'Targosz, Angelina', 'Engelhart, Susanne', 'Herzhoff, Michael', 'Prahm, Kerstin', 'Buda, Silke', 'Nitsche, Andreas', 'Haas, Walter', 'Buchholz, Udo']",Influenza Other Respir Viruses,,,True
e59da8ad79490ad5270928bd54c9a4d0b417d1ee,PMC,"Metagenomic next-generation sequencing of samples from pediatric febrile illness in Tororo, Uganda",http://dx.doi.org/10.1371/journal.pone.0218318,PMC6586300,31220115,CC BY,"Febrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. In this retrospective exploratory study, we used metagenomic next-generation sequencing (mNGS) to evaluate serum, nasopharyngeal, and stool specimens from 94 children (aged 2–54 months) with febrile illness admitted to Tororo District Hospital, Uganda. The most common microbes identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from serum; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. We also report the near complete genome of a highly divergent orthobunyavirus, tentatively named Nyangole virus, identified from the serum of a child diagnosed with malaria and pneumonia, a Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis, and the genomes of two novel human rhinovirus C species. In this retrospective exploratory study, mNGS identified multiple potential pathogens, including 3 new viral species, associated with fever in Ugandan children.",2019 Jun 20,"['Ramesh, Akshaya', 'Nakielny, Sara', 'Hsu, Jennifer', 'Kyohere, Mary', 'Byaruhanga, Oswald', 'de Bourcy, Charles', 'Egger, Rebecca', 'Dimitrov, Boris', 'Juan, Yun-Fang', 'Sheu, Jonathan', 'Wang, James', 'Kalantar, Katrina', 'Langelier, Charles', 'Ruel, Theodore', 'Mpimbaza, Arthur', 'Wilson, Michael R.', 'Rosenthal, Philip J.', 'DeRisi, Joseph L.']",PLoS One,,,True
0666ca679df1885492aa1420fd995790d363b8a5,PMC,Selective use of primate CD4 receptors by HIV-1,http://dx.doi.org/10.1371/journal.pbio.3000304,PMC6586362,31181085,CC BY,"Individuals chronically infected with HIV-1 harbor complex viral populations within their bloodstreams. Recently, it has come to light that when these people infect others, the new infection is typically established by only one or a small number of virions from within this complex viral swarm. An important goal is to characterize the biological properties of HIV-1 virions that seed and exist early in new human infections because these are potentially the only viruses against which a prophylactic HIV-1 vaccine would need to elicit protection. This includes understanding how the Envelope (Env) protein of these virions interacts with the T-cell receptor CD4, which supports attachment and entry of HIV-1 into target cells. We examined early HIV-1 isolates for their ability to infect cells via the CD4 receptor of 15 different primate species. Primates were the original source of HIV-1 and now serve as valuable animal models for studying HIV-1. We find that most primary isolates of HIV-1 from the blood, including early isolates, are highly selective and enter cells through some primate CD4 receptor orthologs but not others. This phenotype is remarkably consistent, regardless of route of transmission, viral subtype, or time of isolation post infection. We show that the weak CD4 binding affinity of blood-derived HIV-1 isolates is what makes them sensitive to the small sequence differences in CD4 from one primate species to the next. To substantiate this, we engineered an early HIV-1 Env to have high, medium, or low binding affinity to CD4, and we show that it loses the ability to enter cells via the CD4 receptor of many primate species as the binding affinity gets weaker. Based on the phenotype of selective use of primate CD4, we find that weak CD4 binding appears to be a nearly universal property of HIV-1 circulating in the bloodstream. Therefore, weak binding to CD4 must be a selected and important property in the biology of HIV-1 in the body. We identify six primate species that encode CD4 receptors that fully support the entry of early HIV-1 isolates despite their low binding affinity for CD4. These findings will help inform long-standing efforts to model HIV-1 transmission and early disease in primates.",2019 Jun 10,"['Warren, Cody J.', 'Meyerson, Nicholas R.', 'Dirasantha, Obaiah', 'Feldman, Emily R.', 'Wilkerson, Gregory K.', 'Sawyer, Sara L.']",PLoS Biol,,,True
073bf7a5962595098cf9d08109b0db9ea1cb3303,PMC,The 2(nd) sialic acid-binding site of influenza A virus neuraminidase is an important determinant of the hemagglutinin-neuraminidase-receptor balance,http://dx.doi.org/10.1371/journal.ppat.1007860,PMC6586374,31181126,CC BY,"Influenza A virus (IAV) neuraminidase (NA) receptor-destroying activity and hemagglutinin (HA) receptor-binding affinity need to be balanced with the host receptor repertoire for optimal viral fitness. NAs of avian, but not human viruses, contain a functional 2(nd) sialic acid (SIA)-binding site (2SBS) adjacent to the catalytic site, which contributes to sialidase activity against multivalent substrates. The receptor-binding specificity and potentially crucial contribution of the 2SBS to the HA-NA balance of virus particles is, however, poorly characterized. Here, we elucidated the receptor-binding specificity of the 2SBS of N2 NA and established an important role for this site in the virion HA-NA-receptor balance. NAs of H2N2/1957 pandemic virus with or without a functional 2SBS and viruses containing this NA were analysed. Avian-like N2, with a restored 2SBS due to an amino acid substitution at position 367, was more active than human N2 on multivalent substrates containing α2,3-linked SIAs, corresponding with the pronounced binding-specificity of avian-like N2 for these receptors. When introduced into human viruses, avian-like N2 gave rise to altered plaque morphology and decreased replication compared to human N2. An opposite replication phenotype was observed when N2 was combined with avian-like HA. Specific bio-layer interferometry assays revealed a clear effect of the 2SBS on the dynamic interaction of virus particles with receptors. The absence or presence of a functional 2SBS affected virion-receptor binding and receptor cleavage required for particle movement on a receptor-coated surface and subsequent NA-dependent self-elution. The contribution of the 2SBS to virus-receptor interactions depended on the receptor-binding properties of HA and the identity of the receptors used. We conclude that the 2SBS is an important and underappreciated determinant of the HA-NA-receptor balance. The rapid loss of a functional 2SBS in pandemic viruses may have served to balance the novel host receptor-repertoire and altered receptor-binding properties of the corresponding HA protein.",2019 Jun 10,"['Du, Wenjuan', 'Guo, Hongbo', 'Nijman, Vera S.', 'Doedt, Jennifer', 'van der Vries, Erhard', 'van der Lee, Joline', 'Li, Zeshi', 'Boons, Geert-Jan', 'van Kuppeveld, Frank J. M.', 'de Vries, Erik', 'Matrosovich, Mikhail', 'de Haan, Cornelis A. M.']",PLoS Pathog,,,True
4ee3d76ee71e4eac590b1b228fc72dc372cdc16f,PMC,"The Group B Streptococcal surface antigen I/II protein, BspC, interacts with host vimentin to promote adherence to brain endothelium and inflammation during the pathogenesis of meningitis",http://dx.doi.org/10.1371/journal.ppat.1007848,PMC6586375,31181121,CC BY,"Streptococcus agalactiae (Group B Streptococcus, GBS) normally colonizes healthy adults but can cause invasive disease, such as meningitis, in the newborn. To gain access to the central nervous system, GBS must interact with and penetrate brain or meningeal blood vessels; however, the exact mechanisms are still being elucidated. Here, we investigate the contribution of BspC, an antigen I/II family adhesin, to the pathogenesis of GBS meningitis. Disruption of the bspC gene reduced GBS adherence to human cerebral microvascular endothelial cells (hCMEC), while heterologous expression of BspC in non-adherent Lactococcus lactis conferred bacterial attachment. In a murine model of hematogenous meningitis, mice infected with ΔbspC mutants exhibited lower mortality as well as decreased brain bacterial counts and inflammatory infiltrate compared to mice infected with WT GBS strains. Further, BspC was both necessary and sufficient to induce neutrophil chemokine expression. We determined that BspC interacts with the host cytoskeleton component vimentin and confirmed this interaction using a bacterial two-hybrid assay, microscale thermophoresis, immunofluorescent staining, and imaging flow cytometry. Vimentin null mice were protected from WT GBS infection and also exhibited less inflammatory cytokine production in brain tissue. These results suggest that BspC and the vimentin interaction is critical for the pathogenesis of GBS meningitis.",2019 Jun 10,"['Deng, Liwen', 'Spencer, Brady L.', 'Holmes, Joshua A.', 'Mu, Rong', 'Rego, Sara', 'Weston, Thomas A.', 'Hu, Yoonsung', 'Sanches, Glenda F.', 'Yoon, Sunghyun', 'Park, Nogi', 'Nagao, Prescilla E.', 'Jenkinson, Howard F.', 'Thornton, Justin A.', 'Seo, Keun Seok', 'Nobbs, Angela H.', 'Doran, Kelly S.']",PLoS Pathog,,,True
c6b7bfae68c5c25203f76616c028668feea39e8e,PMC,Complement Receptor 1 availability on red blood cell surface modulates Plasmodium vivax invasion of human reticulocytes,http://dx.doi.org/10.1038/s41598-019-45228-6,PMC6586822,31221984,CC BY,"Plasmodium vivax parasites preferentially invade reticulocyte cells in a multistep process that is still poorly understood. In this study, we used ex vivo invasion assays and population genetic analyses to investigate the involvement of complement receptor 1 (CR1) in P. vivax invasion. First, we observed that P. vivax invasion of reticulocytes was consistently reduced when CR1 surface expression was reduced through enzymatic cleavage, in the presence of naturally low-CR1-expressing cells compared with high-CR1-expressing cells, and with the addition of soluble CR1, a known inhibitor of P. falciparum invasion. Immuno-precipitation experiments with P. vivax Reticulocyte Binding Proteins showed no evidence of complex formation. In addition, analysis of CR1 genetic data for worldwide human populations with different exposure to malaria parasites show significantly higher frequency of CR1 alleles associated with low receptor expression on the surface of RBCs and higher linkage disequilibrium in human populations exposed to P. vivax malaria compared with unexposed populations. These results are consistent with a positive selection of low-CR1-expressing alleles in vivax-endemic areas. Collectively, our findings demonstrate that CR1 availability on the surface of RBCs modulates P. vivax invasion. The identification of new molecular interactions is crucial to guiding the rational development of new therapeutic interventions against vivax malaria.",2019 Jun 20,"['Prajapati, Surendra Kumar', 'Borlon, Céline', 'Rovira-Vallbona, Eduard', 'Gruszczyk, Jakub', 'Menant, Sebastien', 'Tham, Wai-Hong', 'Kattenberg, Johanna Helena', 'Villasis, Elizabeth', 'De Meulenaere, Katlijn', 'Gamboa, Dionicia', 'Vinetz, Joseph', 'Fujita, Ricardo', 'Xuan, Xa Nguyen', 'Urbano Ferreira, Marcelo', 'Niño, Carlos H.', 'Patarroyo, Manuel A.', 'Spanakos, Gregory', 'Kestens, Luc', 'Abbeele, Jan Van Den', 'Rosanas-Urgell, Anna']",Sci Rep,,,True
e5ee15de8957e84cfbf319bab265ba89d8c98a21,PMC,DCGR: feature extractions from protein sequences based on CGR via remodeling multiple information,http://dx.doi.org/10.1186/s12859-019-2943-x,PMC6587251,31221087,CC BY,"BACKGROUND: Protein feature extraction plays an important role in the areas of similarity analysis of protein sequences and prediction of protein structures, functions and interactions. The feature extraction based on graphical representation is one of the most effective and efficient ways. However, most existing methods suffer limitations from their method design. RESULTS: We introduce DCGR, a novel method for extracting features from protein sequences based on the chaos game representation, which is developed by constructing CGR curves of protein sequences according to physicochemical properties of amino acids, followed by converting the CGR curves into multi-dimensional feature vectors by using the distributions of points in CGR images. Tested on five data sets, DCGR was significantly superior to the state-of-the-art feature extraction methods. CONCLUSION: The DCGR is practically powerful for extracting effective features from protein sequences, and therefore important in similarity analysis of protein sequences, study of protein-protein interactions and prediction of protein functions. It is freely available at https://sourceforge.net/projects/transcriptomeassembly/files/Feature%20Extraction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-019-2943-x) contains supplementary material, which is available to authorized users.",2019 Jun 20,"['Mu, Zengchao', 'Yu, Ting', 'Qi, Enfeng', 'Liu, Juntao', 'Li, Guojun']",BMC Bioinformatics,,,False
5350a5cc254f384ba7c7c0f36e0d2383c47d6f55,PMC,DCGR: feature extractions from protein sequences based on CGR via remodeling multiple information,http://dx.doi.org/10.1186/s12859-019-2943-x,PMC6587251,31221087,CC BY,"BACKGROUND: Protein feature extraction plays an important role in the areas of similarity analysis of protein sequences and prediction of protein structures, functions and interactions. The feature extraction based on graphical representation is one of the most effective and efficient ways. However, most existing methods suffer limitations from their method design. RESULTS: We introduce DCGR, a novel method for extracting features from protein sequences based on the chaos game representation, which is developed by constructing CGR curves of protein sequences according to physicochemical properties of amino acids, followed by converting the CGR curves into multi-dimensional feature vectors by using the distributions of points in CGR images. Tested on five data sets, DCGR was significantly superior to the state-of-the-art feature extraction methods. CONCLUSION: The DCGR is practically powerful for extracting effective features from protein sequences, and therefore important in similarity analysis of protein sequences, study of protein-protein interactions and prediction of protein functions. It is freely available at https://sourceforge.net/projects/transcriptomeassembly/files/Feature%20Extraction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-019-2943-x) contains supplementary material, which is available to authorized users.",2019 Jun 20,"['Mu, Zengchao', 'Yu, Ting', 'Qi, Enfeng', 'Liu, Juntao', 'Li, Guojun']",BMC Bioinformatics,,,True
b8423ebcd07e62c48ca7205a06fee753f9199e58,PMC,"Assessing dengue control in Tokyo, 2014",http://dx.doi.org/10.1371/journal.pntd.0007468,PMC6588210,31226116,CC BY,"BACKGROUND: In summer 2014, an autochthonous outbreak of dengue occurred in Tokyo, Japan, in which Yoyogi Park acted as the focal area of transmission. Recognizing the outbreak, concerted efforts were made to control viral spread, which included mosquito control, public announcement of the outbreak, and a total ban on entering the park. We sought to assess the effectiveness of these control measures. METHODOLOGY/PRINCIPAL FINDINGS: We used a mathematical model to describe the transmission dynamics. Using dates of exposure and illness onset, we categorized cases into three groups according to the availability of these datasets. The infection process was parametrically modeled by generation, and convolution of the infection process and the incubation period was fitted to the data. By estimating the effective reproduction number, we determined that the effect of dengue risk communication together with mosquito control from 28 August 2014 was insufficiently large to lower the reproduction number to below 1. However, once Yoyogi Park was closed on 4 September, the value of the effective reproduction number began to fall below 1, and the associated relative reduction in the effective reproduction number was estimated to be 20%–60%. The mean incubation period was an estimated 5.8 days. CONCLUSIONS/SIGNIFICANCE: Regardless of the assumed number of generations of cases, the combined effect of mosquito control, risk communication, and park closure appeared to be successful in interrupting the chain of dengue transmission in Tokyo.",2019 Jun 21,"['Yuan, Baoyin', 'Lee, Hyojung', 'Nishiura, Hiroshi']",PLoS Negl Trop Dis,,,True
8d94c10b7cac018c7bd1b9c1c58365b78b35b458,PMC,Comparing the yield of oropharyngeal swabs and sputum for detection of 11 common pathogens in hospitalized children with lower respiratory tract infection,http://dx.doi.org/10.1186/s12985-019-1177-x,PMC6591818,31234918,CC BY,"BACKGROUND: Advances in molecular laboratory techniques are changing the prospects for the diagnosis of viral infectious diseases. Multiplex polymerase chain reaction assay (multiplex-PCR) can detect dozens of pathogens simultaneously, greatly reducing turnaround time (TAT) and improving detection sensitivity. But as a double-edged sword, due to the high sensitivity of PCR, the type of respiratory specimens is critical to diagnosis. In this work, we performed a head-to-head comparison to evaluate the multiplex-PCR yields between two samples, sputum and flocked oropharyngeal swabs (OPS). METHODS: Eleven common respiratory pathogens were tested in hospitalized children< 13 years of age who met the criteria for lower respiratory tract infection by GeXP-based multiplex-PCR of paired OPS and sputum. RESULTS: From January to June 2018, 440 children with paired OPS and sputum were tested. The positive rate was 84% (369/440) for OPS and 88% (386/440) for sputum (p = .007). The frequency of detection of HRV, RSV, Influenza A virus, HMPV, parainfluenza virus, adenovirus, M. pneumoniae, coronavirus, bocavirus and C. pneumoniae in sputa was higher than that of OPSs (all p < .001). Both types of specimens had similarly very good kappa values for most of pathogens, except for Mycoplasma pneumonia (κ = 0.61) and Chlamydia pneumoniae (κ = 0.24). Additionally, 79.3% (349/440) of cases showed consistent results between the two types of samples, and they were significantly younger than patients with inconsistent results (p = .002). CONCLUSIONS: Flocked oropharyngeal swabs and sputum performed similarly for the detection of common respiratory pathogens in hospitalized children by multiplex-PCR, except for Mycoplasma pneumoniae and Chlamydia pneumoniae. Young patients are likely to have consistent results between the two specimens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-019-1177-x) contains supplementary material, which is available to authorized users.",2019 Jun 24,"['Wang, Le', 'Yang, Shuo', 'Yan, Xiaotong', 'Liu, Teng', 'Feng, Zhishan', 'Li, Guixia']",Virol J,,,True
40825b0106c7d8664276f75be3df4a75fb046c44,PMC,Protocol for development of a risk assessment tool for planning and management of religious mass-gathering events of India—a health system-strengthening initiative,http://dx.doi.org/10.1186/s40814-019-0464-z,PMC6591856,31293791,CC BY,"BACKGROUND: Religious mass gatherings (MGs) have always been an integral part of our society. At the outset, mass-gathering events provide challenging settings to plan a suitable emergency public health response. Published studies basically talk about retrospective reviews, case studies of the public health preparedness, or health care provided at individual events. Developing an understanding of the variables associated with MGs is the first step for public health managers. Risk assessment (RA) is a crucial part of pre-event planning as it helps foresee potential risks. Based on RA, one can develop preventive measures and ensure that the infrastructure to control the potential problems is in place. This study is an attempt to systemize RA process during MG events in a country that is culturally rich but with poor resources to handle such events. A RA tool will be developed for planning and management of religious MG events of India. METHODS/DESIGN: Various strategies will be used to develop the risk assessment tool (RA tool). Extensive review of literature clubbed with key informant interviews will be done in order to identify the risk variables and decide the domains and items of the tool. Further, this tool will be developed as a mobile-based application. The feasibility of the mobile-based RA tool will be tested in real-time MG event in one part of the country. Concurrently in the same event, a community survey of residents and visitors will be done in order to assess public perceptions of public health and environmental risks associated with MG events. DISCUSSION: The findings of this study will provide insights into the public health and environmental concerns that need to be considered if preventive strategies and intervention programs are to be designed for MG events. A “RA Tool,” which can be used in the planning and management of MG events by the public health managers will strengthen the existing health systems preparedness plans for MGs.",2019 Jun 24,"['Sharma, Upasana', 'Desikachari, B. R.', 'Sarma, Sankara']",Pilot Feasibility Stud,,,True
b4a97db27c8eaeb487a83a37c4bf05cd31abebf8,PMC,Genomic characterization of canine circovirus associated with fatal disease in dogs in South America,http://dx.doi.org/10.1371/journal.pone.0218735,PMC6592543,31237902,CC BY,"Canine circovirus (CanineCV) was detected, together with canine parvovirus (CPV), in samples from an outbreak of fatal gastroenteritis in dogs in Argentina. We obtained the full-length genome of this recently discovered virus by overlapping PCR, designated strain UBA-Baires. Sequence analysis revealed a highly conserved genome but also showed several unique mutations in amino acids from the capsid protein that have not been previously reported. Phylogenetic analysis shows that this strain is more closely related to European strains than to viruses detected in North America or Asia. Although the pathogenic role of CanineCV in dogs is still unclear, this study highlights the importance of CanineCV as a coinfecting virus in disease development. To our knowledge, this is the first report of the involvement of CanineCV in severe clinical disease in dogs in South America. Our results expand our information on the geographical extent of this virus and contribute to the understanding of its role in disease.",2019 Jun 25,"['Kotsias, Fiorella', 'Bucafusco, Danilo', 'Nuñez, Denise Anabel', 'Lago Borisovsky, Lucía Antonella', 'Rodriguez, Mariana', 'Bratanich, Ana Cristina']",PLoS One,,,True
57eb57853f082c4b343cb136c248c9b14f5e632c,PMC,Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies,http://dx.doi.org/10.1371/journal.ppat.1007819,PMC6592578,31194843,CC0,"Recently identified broadly neutralizing antibodies (bnAbs) show great potential for clinical interventions against HIV-1 infection. However, resistant strains may impose substantial challenges. Here, we report on the identification and characterization of a panel of HIV-1 strains with broad and potent resistance against a large number of bnAbs, particularly those targeting the CD4-binding site (CD4bs). Site-directed mutagenesis revealed that several key epitope mutations facilitate resistance and are located in the inner domain, loop D, and β23/loop V5/β24 of HIV-1 gp120. The resistance is largely correlated with binding affinity of antibodies to the envelope trimers expressed on the cell surface. Our results therefore demonstrate the existence of broadly resistant HIV-1 strains against CD4bs neutralizing antibodies. Treatment strategies based on the CD4bs bnAbs must overcome such resistance to achieve optimal clinical outcomes.",2019 Jun 13,"['Zhou, Panpan', 'Wang, Han', 'Fang, Mengqi', 'Li, Yangyang', 'Wang, Hua', 'Shi, Shasha', 'Li, Zihao', 'Wu, Jiapeng', 'Han, Xiaoxu', 'Shi, Xuanling', 'Shang, Hong', 'Zhou, Tongqing', 'Zhang, Linqi']",PLoS Pathog,,,True
740a68304e37d9c1e1ab4bf433594a5a47179c61,PMC,Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies,http://dx.doi.org/10.1371/journal.ppat.1007819,PMC6592578,31194843,CC0,"Recently identified broadly neutralizing antibodies (bnAbs) show great potential for clinical interventions against HIV-1 infection. However, resistant strains may impose substantial challenges. Here, we report on the identification and characterization of a panel of HIV-1 strains with broad and potent resistance against a large number of bnAbs, particularly those targeting the CD4-binding site (CD4bs). Site-directed mutagenesis revealed that several key epitope mutations facilitate resistance and are located in the inner domain, loop D, and β23/loop V5/β24 of HIV-1 gp120. The resistance is largely correlated with binding affinity of antibodies to the envelope trimers expressed on the cell surface. Our results therefore demonstrate the existence of broadly resistant HIV-1 strains against CD4bs neutralizing antibodies. Treatment strategies based on the CD4bs bnAbs must overcome such resistance to achieve optimal clinical outcomes.",2019 Jun 13,"['Zhou, Panpan', 'Wang, Han', 'Fang, Mengqi', 'Li, Yangyang', 'Wang, Hua', 'Shi, Shasha', 'Li, Zihao', 'Wu, Jiapeng', 'Han, Xiaoxu', 'Shi, Xuanling', 'Shang, Hong', 'Zhou, Tongqing', 'Zhang, Linqi']",PLoS Pathog,,,False
b7f090aebd3ca0c64361662b87a6134c0afacb1a,PMC,Middle East Respiratory Syndrome Coronavirus in Dromedaries in Ethiopia Is Antigenically Different From the Middle East Isolate EMC,http://dx.doi.org/10.3389/fmicb.2019.01326,PMC6593072,31275264,CC BY,"Middle East respiratory syndrome (MERS) is an emerging respiratory disease caused by the MERS coronavirus (MERS-CoV). MERS has been endemic to Saudi Arabia since 2012. The reservoir of MERS-CoV is the dromedary camel, suggesting that MERS is primarily a zoonotic disease. MERS-CoV is common in dromedaries throughout the Middle East, North Africa, and East Africa as evidenced by neutralizing antibodies against MERS-CoV; however, human cases have remained limited to the Middle East. To better understand the cause of this difference, the virological properties of African camel MERS-CoV were analyzed based on the spike (S) protein in Ethiopia. Nasal swabs were collected from 258 young dromedaries (≤ 2 years old) in the Afar region of Ethiopia, of which 39 were positive for MERS-CoV, as confirmed by genetic tests. All positive tests were exclusive to the Amibara woreda region. Using next-generation sequencing, two full-length genomes of Amibara isolates were successfully decoded; both isolates belonged to the C2 clade based on phylogenetic analysis of full-length and S protein sequences. Recombinant EMC isolates of MERS-CoV, in which the S protein is replaced with those of Amibara isolates, were then generated to test the roles of these proteins in viral properties. Amibara S recombinants replicated more slowly in cultured cells than in EMC S recombinants. In neutralizing assays, Amibara S recombinants were neutralized by lower concentrations of sera from both Ethiopian dromedaries and EMC isolate (wild-type)-immunized mouse sera, relative to the EMC S recombinants, indicating that viruses coated in the Amibara S protein were easier to neutralize than the EMC S protein. Neutralization experiments performed using S1/S2 chimeric recombinants of the EMC and Amibara S proteins showed that the neutralization profile was dependent on the S1 region of the S protein. These results suggest that the slower viral replication and the ease of neutralization seen in the Ethiopian MERS-CoV are due to strain-specific differences in the S protein and may account for the absence of human MERS-CoV cases in Ethiopia.",2019 Jun 19,"['Shirato, Kazuya', 'Melaku, Simenew Keskes', 'Kawachi, Kengo', 'Nao, Naganori', 'Iwata-Yoshikawa, Naoko', 'Kawase, Miyuki', 'Kamitani, Wataru', 'Matsuyama, Shutoku', 'Tessema, Tesfaye Sisay', 'Sentsui, Hiroshi']",Front Microbiol,,,True
e5746d8d6badecb0d0afc06192c540aed6479c83,PMC,Identification of a Novel Non-desmoglein Autoantigen in Pemphigus Vulgaris,http://dx.doi.org/10.3389/fimmu.2019.01391,PMC6593111,31275324,CC BY,"Pemphigus vulgaris (PV) is an autoimmune bullous disease of the skin and mucous membranes characterized by the presence of circulating and tissue-bound autoantibodies against keratinocyte cell surface antigens, specifically desmoglein (Dsg) 1 and 3. The pathogenic role of anti-Dsg antibodies is well-established, while the mechanism of blister formation is only partly defined. We have applied a previously developed method for the efficient immortalization of IgG+ memory B cells to identify novel target antigens in PV. A human monoclonal antibody reactive with a hitherto unreported non-Dsg antigen was isolated. Immunoprecipitation and immunoblotting studies with keratinocyte extracts indicated α-catenin as the putative antigen, then confirmed by immunoblotting on the recombinant protein. Four of ten PV sera reacted with recombinant α-catenin. Although the isolated human monoclonal antibody was per se unable to dissociate keratinocyte monolayers and also to synergize with a pathogenic antibody in vitro, further studies are warranted to assess its possible in vivo contribution in the multifactorial pathogenesis and heterogeneous manifestations of PV disease.",2019 Jun 19,"['Di Lullo, Giulia', 'Calabresi, Valentina', 'Mariotti, Feliciana', 'Zambruno, Giovanna', 'Lanzavecchia, Antonio', 'Di Zenzo, Giovanni']",Front Immunol,,,True
314ad98da0441adaf164682e8c74b0124575f402,PMC,Identification of a Novel Non-desmoglein Autoantigen in Pemphigus Vulgaris,http://dx.doi.org/10.3389/fimmu.2019.01391,PMC6593111,31275324,CC BY,"Pemphigus vulgaris (PV) is an autoimmune bullous disease of the skin and mucous membranes characterized by the presence of circulating and tissue-bound autoantibodies against keratinocyte cell surface antigens, specifically desmoglein (Dsg) 1 and 3. The pathogenic role of anti-Dsg antibodies is well-established, while the mechanism of blister formation is only partly defined. We have applied a previously developed method for the efficient immortalization of IgG+ memory B cells to identify novel target antigens in PV. A human monoclonal antibody reactive with a hitherto unreported non-Dsg antigen was isolated. Immunoprecipitation and immunoblotting studies with keratinocyte extracts indicated α-catenin as the putative antigen, then confirmed by immunoblotting on the recombinant protein. Four of ten PV sera reacted with recombinant α-catenin. Although the isolated human monoclonal antibody was per se unable to dissociate keratinocyte monolayers and also to synergize with a pathogenic antibody in vitro, further studies are warranted to assess its possible in vivo contribution in the multifactorial pathogenesis and heterogeneous manifestations of PV disease.",2019 Jun 19,"['Di Lullo, Giulia', 'Calabresi, Valentina', 'Mariotti, Feliciana', 'Zambruno, Giovanna', 'Lanzavecchia, Antonio', 'Di Zenzo, Giovanni']",Front Immunol,,,False
4753feb97a6db2b1172caa96791e23e96ac9d287,PMC,A Randomized Double Blinded Placebo-Controlled Clinical Trial of a Probiotic or Metronidazole for Acute Canine Diarrhea,http://dx.doi.org/10.3389/fvets.2019.00163,PMC6593266,31275948,CC BY,"Acute diarrhea is a common, often self-limiting, cause of presentation for veterinary care, yet there is a paucity of data on frequently-prescribed treatments. The purpose of this randomized, double blinded placebo-controlled clinical trial was to compare two anecdotally-recommended treatments: a probiotic combination and metronidazole. Sixty dogs without concurrent comorbidities were randomized into three treatment groups. The time to resolution of diarrheal signs was evaluated using owner surveys and fecal scoring charts. Dogs presenting with acute diarrhea achieved acceptable fecal consistency after 3.5 ± 2.2 days when receiving probiotic, 4.6 ± 2.4 days with oral metronidazole, and 4.8 ± 2.9 days with placebo; statistically significant differences were not identified between treatment groups (p = 0.17). These findings failed to provide evidence for the common use of metronidazole in this cohort of dogs with acute canine diarrhea, and a larger study population would be required to identify a statistically significant effect of probiotics.",2019 Jun 4,"['Shmalberg, Justin', 'Montalbano, Christina', 'Morelli, Giada', 'Buckley, Gareth J.']",Front Vet Sci,,,True
396a42500c39667896d3e7b918422af5854d7439,PMC,Multiplex Platforms for the Identification of Respiratory Pathogens: Are They Useful in Pediatric Clinical Practice?,http://dx.doi.org/10.3389/fcimb.2019.00196,PMC6593267,31275863,CC BY,"Respiratory tract infections (RTIs) are extremely common especially in the first year of life. Knowledge of the etiology of a RTI is essential to facilitate the appropriate management and the implementation of the most effective control measures. This perspective explains why laboratory methods that can identify pathogens in respiratory secretions have been developed over the course of many years. High-complexity multiplex panel assays that can simultaneously detect up to 20 viruses and up to four bacteria within a few hours have been marketed. However, are these platforms actually useful in pediatric clinical practice? In this manuscript, we showed that these platforms appear to be particularly important for epidemiological studies and clinical research. On the contrary, their routine use in pediatric clinical practice remains debatable. They can be used only in the hospital as they require specific equipment and laboratory technicians with considerable knowledge, training, and experience. Moreover, despite more sensitive and specific than other tests routinely used for respiratory pathogen identification, they do not offer significantly advantage for detection of the true etiology of a respiratory disease. Furthermore, knowledge of which virus is the cause of a respiratory disease is not useful from a therapeutic point of view unless influenza virus or respiratory syncytial virus are the infecting agents as effective drugs are available only for these pathogens. On the other hand, multiplex platforms can be justified in the presence of severe clinical manifestations, and in immunocompromised patients for whom specific treatment option can be available, particularly when they can be used simultaneously with platforms that allow identification of antimicrobial resistance to commonly used drugs. It is highly likely that these platforms, particularly those with high sensitivity and specificity and with low turnaround time, will become essential when new drugs effective and safe against most of the respiratory viruses will be available. Further studies on how to differentiate carriers from patients with true disease, as well as studies on the implications of coinfections and identification of antimicrobial resistance, are warranted.",2019 Jun 4,"['Esposito, Susanna', 'Mencacci, Antonella', 'Cenci, Elio', 'Camilloni, Barbara', 'Silvestri, Ettore', 'Principi, Nicola']",Front Cell Infect Microbiol,,,True
40ac6a37f332f47ff9e9c6a6f8b1d5d21752679e,PMC,"Overview of Current Therapeutics and Novel Candidates Against Influenza, Respiratory Syncytial Virus, and Middle East Respiratory Syndrome Coronavirus Infections",http://dx.doi.org/10.3389/fmicb.2019.01327,PMC6594388,31275265,CC BY,"Emergence and re-emergence of respiratory virus infections represent a significant threat to global public health, as they occur seasonally and less frequently (such as in the case of influenza virus) as pandemic infections. Some of these viruses have been in the human population for centuries and others had recently emerged as a public health problem. Influenza viruses have been affecting the human population for a long time now; however, their ability to rapidly evolve through antigenic drift and antigenic shift causes the emergence of new strains. A recent example of these events is the avian-origin H7N9 influenza virus outbreak currently undergoing in China. Human H7N9 influenza viruses are resistant to amantadines and some strains are also resistant to neuraminidase inhibitors greatly limiting the options for treatment. Respiratory syncytial virus (RSV) may cause a lower respiratory tract infection characterized by bronchiolitis and pneumonia mainly in children and the elderly. Infection with RSV can cause severe disease and even death, imposing a severe burden for pediatric and geriatric health systems worldwide. Treatment for RSV is mainly supportive since the only approved therapy, a monoclonal antibody, is recommended for prophylactic use in high-risk patients. The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging respiratory virus. The virus was first recognized in 2012 and it is associated with a lower respiratory tract disease that is more severe in patients with comorbidities. No licensed vaccines or antivirals have been yet approved for the treatment of MERS-CoV in humans. It is clear that the discovery and development of novel antivirals that can be used alone or in combination with existing therapies to treat these important respiratory viral infections are critical. In this review, we will describe some of the novel therapeutics currently under development for the treatment of these infections.",2019 Jun 19,"['Behzadi, Mohammad Amin', 'Leyva-Grado, Victor H.']",Front Microbiol,,,True
0ed2c41c3728dac9545af1c1b608fb25063c617a,PMC,Plant Viruses in Plant Molecular Pharming: Toward the Use of Enveloped Viruses,http://dx.doi.org/10.3389/fpls.2019.00803,PMC6594412,31275344,CC BY,"Plant molecular pharming has emerged as a reliable platform for recombinant protein expression providing a safe and low-cost alternative to bacterial and mammalian cells-based systems. Simultaneously, plant viruses have evolved from pathogens to molecular tools for recombinant protein expression, chimaeric viral vaccine production, and lately, as nanoagents for drug delivery. This review summarizes the genesis of viral vectors and agroinfection, the development of non-enveloped viruses for various biotechnological applications, and the on-going research on enveloped plant viruses.",2019 Jun 19,"['Ibrahim, Ahmad', 'Odon, Valerie', 'Kormelink, Richard']",Front Plant Sci,,,True
eba0fa2089d19236b36e5b786c1d60e1d083f738,PMC,Relationship of α2‐Macroglobulin with Steroid‐Induced Femoral Head Necrosis: A Chinese Population‐Based Association Study in Southeast China,http://dx.doi.org/10.1111/os.12492,PMC6595108,31243924,CC BY,"OBJECTIVE: The present study aimed to identify the relationship of α‐2‐macroglobulin and microvascular vessel pathology with steroid‐induced femoral head necrosis in the Southeast Chinese population. METHODS: This study enrolled 40 patients diagnosed with steroid‐induced necrosis of the femoral head. Patients had various stages of femoral head necrosis. The differential expression of serum proteins and mRNA from patients with steroid‐induced necrosis of the femoral head (SINFH) and healthy volunteers was analyzed by western blot and quantitative polymerase chain reaction (QT‐PCR). The pathological change in osteocyte necrosis was indicated by hematoxylin and eosin stain and immunohistochemistry. RESULTS: Hematoxylin and eosin stain showed histopathology changes in the necrotic area of patients with steroid‐induced INFH: bone trabeculae were fewer and thinner, became broken, fragmented and structurally disordered; intraosseous adipose cells became enlarged; the arrangement of the osteoblasts became irregular; and vacant bone lacunae increased. QT‐PCR showed significantly lower levels of α‐2‐macroglobulin in the serum of patients with SINFH than in controls (P < 0.05). Immunohistochemical staining and western blotting demonstrated that the expression of α‐2‐macroglobulin was significantly decreased in the necrotic area of SINFH patients (P < 0.05). CONCLUSION: The α‐2‐macroglobulin may be associated with the pathology of SINFH. The multiple pathological reactions occur in SINFH and α‐2‐macroglobulin may serve as a potential biomarker for the diagnosis of SINFH or a promising therapeutic target.",2019 Jun 26,"['Fang, Shan‐hong', 'Li, Yong‐feng', 'Jiang, Jia‐run', 'Chen, Peng']",Orthop Surg,,,True
a70d334286efa96684bd35e383175063c285ab8b,PMC,Molecular characterization of type 1 porcine reproductive and respiratory syndrome viruses (PRRSV) isolated in the Netherlands from 2014 to 2016,http://dx.doi.org/10.1371/journal.pone.0218481,PMC6597066,31246977,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of a devastating pig disease present all over the world. The remarkable genetic variation of PRRSV, makes epidemiological and molecular analysis of circulating viruses highly important to review current diagnostic tools and vaccine efficacy. Monitoring PRRS viruses supports modern herd management by explaining the source of found viruses, either internally or externally from the herd. No epidemiological or molecular study has been published on circulating PRRS-viruses in the Netherlands, since the early nineties. Therefore, the objective of this study is to investigate circulating PRRS-viruses in the Netherlands in 2014, 2015 and 2016 on a molecular level by sequencing ORF2, ORF3, ORF4, ORF5, ORF6 and ORF7. The results demonstrate that the 74 PRRSV strains belong to PRRSV-1, but the diversity among strains is high, based on nucleotide identity, individual ORF length and phylogenetic trees of individual ORFs. Furthermore, the data presented here show that the phylogenetic topology of some viruses is ORF dependent and suggests recombination. The identity of the strain of interest might be misinterpreted and wrong conclusions may be drawn in a diagnostic and epidemiological perspective, when only ORF5 is analyzed, as performed in many routine sequencing procedures.",2019 Jun 27,"['Dortmans, J. C. F. M.', 'Buter, G. J.', 'Dijkman, R.', 'Houben, M.', 'Duinhof, T. F.']",PLoS One,,,True
e00c847f349e8515e672e4bc066ca7296499cadd,PMC,Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis,http://dx.doi.org/10.1038/s41467-019-10687-y,PMC6597546,31249291,CC BY,"Cryptosporidiosis is a leading cause of life-threatening diarrhea in young children and causes chronic diarrhea in AIDS patients, but the only approved treatment is ineffective in malnourished children and immunocompromised people. We here use a drug repositioning strategy and identify a promising anticryptosporidial drug candidate. Screening a library of benzoxaboroles comprised of analogs to four antiprotozoal chemical scaffolds under pre-clinical development for neglected tropical diseases for Cryptosporidium growth inhibitors identifies the 6-carboxamide benzoxaborole AN7973. AN7973 blocks intracellular parasite development, appears to be parasiticidal, and potently inhibits the two Cryptosporidium species most relevant to human health, C. parvum and C. hominis. It is efficacious in murine models of both acute and established infection, and in a neonatal dairy calf model of cryptosporidiosis. AN7973 also possesses favorable safety, stability, and PK parameters, and therefore, is an exciting drug candidate for treating cryptosporidiosis.",2019 Jun 27,"['Lunde, Christopher S.', 'Stebbins, Erin E.', 'Jumani, Rajiv S.', 'Hasan, Md Mahmudul', 'Miller, Peter', 'Barlow, John', 'Freund, Yvonne R.', 'Berry, Pamela', 'Stefanakis, Rianna', 'Gut, Jiri', 'Rosenthal, Philip J.', 'Love, Melissa S.', 'McNamara, Case W.', 'Easom, Eric', 'Plattner, Jacob J.', 'Jacobs, Robert T.', 'Huston, Christopher D.']",Nat Commun,,,False
623c896179970f247ddd12e18f6d4d1a6c40b056,PMC,Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis,http://dx.doi.org/10.1038/s41467-019-10687-y,PMC6597546,31249291,CC BY,"Cryptosporidiosis is a leading cause of life-threatening diarrhea in young children and causes chronic diarrhea in AIDS patients, but the only approved treatment is ineffective in malnourished children and immunocompromised people. We here use a drug repositioning strategy and identify a promising anticryptosporidial drug candidate. Screening a library of benzoxaboroles comprised of analogs to four antiprotozoal chemical scaffolds under pre-clinical development for neglected tropical diseases for Cryptosporidium growth inhibitors identifies the 6-carboxamide benzoxaborole AN7973. AN7973 blocks intracellular parasite development, appears to be parasiticidal, and potently inhibits the two Cryptosporidium species most relevant to human health, C. parvum and C. hominis. It is efficacious in murine models of both acute and established infection, and in a neonatal dairy calf model of cryptosporidiosis. AN7973 also possesses favorable safety, stability, and PK parameters, and therefore, is an exciting drug candidate for treating cryptosporidiosis.",2019 Jun 27,"['Lunde, Christopher S.', 'Stebbins, Erin E.', 'Jumani, Rajiv S.', 'Hasan, Md Mahmudul', 'Miller, Peter', 'Barlow, John', 'Freund, Yvonne R.', 'Berry, Pamela', 'Stefanakis, Rianna', 'Gut, Jiri', 'Rosenthal, Philip J.', 'Love, Melissa S.', 'McNamara, Case W.', 'Easom, Eric', 'Plattner, Jacob J.', 'Jacobs, Robert T.', 'Huston, Christopher D.']",Nat Commun,,,False
ee2fc6a943eac54444f75f0fbaf099178e36a11d,PMC,Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis,http://dx.doi.org/10.1038/s41467-019-10687-y,PMC6597546,31249291,CC BY,"Cryptosporidiosis is a leading cause of life-threatening diarrhea in young children and causes chronic diarrhea in AIDS patients, but the only approved treatment is ineffective in malnourished children and immunocompromised people. We here use a drug repositioning strategy and identify a promising anticryptosporidial drug candidate. Screening a library of benzoxaboroles comprised of analogs to four antiprotozoal chemical scaffolds under pre-clinical development for neglected tropical diseases for Cryptosporidium growth inhibitors identifies the 6-carboxamide benzoxaborole AN7973. AN7973 blocks intracellular parasite development, appears to be parasiticidal, and potently inhibits the two Cryptosporidium species most relevant to human health, C. parvum and C. hominis. It is efficacious in murine models of both acute and established infection, and in a neonatal dairy calf model of cryptosporidiosis. AN7973 also possesses favorable safety, stability, and PK parameters, and therefore, is an exciting drug candidate for treating cryptosporidiosis.",2019 Jun 27,"['Lunde, Christopher S.', 'Stebbins, Erin E.', 'Jumani, Rajiv S.', 'Hasan, Md Mahmudul', 'Miller, Peter', 'Barlow, John', 'Freund, Yvonne R.', 'Berry, Pamela', 'Stefanakis, Rianna', 'Gut, Jiri', 'Rosenthal, Philip J.', 'Love, Melissa S.', 'McNamara, Case W.', 'Easom, Eric', 'Plattner, Jacob J.', 'Jacobs, Robert T.', 'Huston, Christopher D.']",Nat Commun,,,True
ca3b60057b15c70f89253eea29c89a187fbc0fdc,PMC,Inferring who-infected-whom-where in the 2016 Zika outbreak in Singapore—a spatio-temporal model,http://dx.doi.org/10.1098/rsif.2018.0604,PMC6597776,31213175,CC BY,"Singapore experienced its first known Zika outbreak in 2016. Given the lack of herd immunity, the suitability of the climate for pathogen transmission, and the year-round presence of the vector—Aedes aegypti—Zika had the potential to become endemic, like dengue. Guillain–Barré syndrome and microcephaly are severe complications associated elsewhere with Zika and the risk of these complications makes understanding its spread imperative. We investigated the spatio-temporal spread of locally transmitted Zika in Singapore and assessed the relevance of non-residential transmission of Zika virus infections, by inferring the possible infection tree (i.e. who-infected-whom-where) and comparing inferences using geographically resolved data on cases' home, their work, or their home and work. We developed a spatio-temporal model using time of onset and both addresses of the Zika-confirmed cases between July and September 2016 to estimate the infection tree using Bayesian data augmentation. Workplaces were involved in a considerable fraction (64.2%) of infections, and homes and workplaces may be distant relative to the scale of transmission, allowing ambulant infected persons may act as the ‘vector’ infecting distant parts of the country. Contact tracing is a challenge for mosquito-borne diseases, but inferring the geographically structured transmission tree sheds light on the spatial transmission of Zika to immunologically naive regions of the country.",2019 Jun 19,"['Prem, Kiesha', 'Lau, Max S. Y.', 'Tam, Clarence C.', 'Ho, Marc Z. J.', 'Ng, Lee-Ching', 'Cook, Alex R.']",J R Soc Interface,,,True
ee6789ddf25ea68748fbc998fa9eb2f81b65302b,PMC,Inferring who-infected-whom-where in the 2016 Zika outbreak in Singapore—a spatio-temporal model,http://dx.doi.org/10.1098/rsif.2018.0604,PMC6597776,31213175,CC BY,"Singapore experienced its first known Zika outbreak in 2016. Given the lack of herd immunity, the suitability of the climate for pathogen transmission, and the year-round presence of the vector—Aedes aegypti—Zika had the potential to become endemic, like dengue. Guillain–Barré syndrome and microcephaly are severe complications associated elsewhere with Zika and the risk of these complications makes understanding its spread imperative. We investigated the spatio-temporal spread of locally transmitted Zika in Singapore and assessed the relevance of non-residential transmission of Zika virus infections, by inferring the possible infection tree (i.e. who-infected-whom-where) and comparing inferences using geographically resolved data on cases' home, their work, or their home and work. We developed a spatio-temporal model using time of onset and both addresses of the Zika-confirmed cases between July and September 2016 to estimate the infection tree using Bayesian data augmentation. Workplaces were involved in a considerable fraction (64.2%) of infections, and homes and workplaces may be distant relative to the scale of transmission, allowing ambulant infected persons may act as the ‘vector’ infecting distant parts of the country. Contact tracing is a challenge for mosquito-borne diseases, but inferring the geographically structured transmission tree sheds light on the spatial transmission of Zika to immunologically naive regions of the country.",2019 Jun 19,"['Prem, Kiesha', 'Lau, Max S. Y.', 'Tam, Clarence C.', 'Ho, Marc Z. J.', 'Ng, Lee-Ching', 'Cook, Alex R.']",J R Soc Interface,,,True
5621482f4f2f4dd6baeb09a6aa2a2cc5fed60fcb,PMC,Inferring who-infected-whom-where in the 2016 Zika outbreak in Singapore—a spatio-temporal model,http://dx.doi.org/10.1098/rsif.2018.0604,PMC6597776,31213175,CC BY,"Singapore experienced its first known Zika outbreak in 2016. Given the lack of herd immunity, the suitability of the climate for pathogen transmission, and the year-round presence of the vector—Aedes aegypti—Zika had the potential to become endemic, like dengue. Guillain–Barré syndrome and microcephaly are severe complications associated elsewhere with Zika and the risk of these complications makes understanding its spread imperative. We investigated the spatio-temporal spread of locally transmitted Zika in Singapore and assessed the relevance of non-residential transmission of Zika virus infections, by inferring the possible infection tree (i.e. who-infected-whom-where) and comparing inferences using geographically resolved data on cases' home, their work, or their home and work. We developed a spatio-temporal model using time of onset and both addresses of the Zika-confirmed cases between July and September 2016 to estimate the infection tree using Bayesian data augmentation. Workplaces were involved in a considerable fraction (64.2%) of infections, and homes and workplaces may be distant relative to the scale of transmission, allowing ambulant infected persons may act as the ‘vector’ infecting distant parts of the country. Contact tracing is a challenge for mosquito-borne diseases, but inferring the geographically structured transmission tree sheds light on the spatial transmission of Zika to immunologically naive regions of the country.",2019 Jun 19,"['Prem, Kiesha', 'Lau, Max S. Y.', 'Tam, Clarence C.', 'Ho, Marc Z. J.', 'Ng, Lee-Ching', 'Cook, Alex R.']",J R Soc Interface,,,False
c77304ebab5efc8f6d8af8b9a04e8614882523e9,PMC,Individual or Common Good? Voluntary Data Sharing to Inform Disease Surveillance Systems in Food Animals,http://dx.doi.org/10.3389/fvets.2019.00194,PMC6598744,31294036,CC BY,"Livestock producers have traditionally been reluctant to share information related to their business, including data on health status of their animals, which, sometimes, has impaired the ability to implement surveillance programs. However, during the last decade, swine producers in the United States (US) and other countries have voluntarily begun to share data for the control and elimination of specific infectious diseases, such as the porcine reproductive and respiratory syndrome virus (PRRSv). Those surveillance programs have played a pivotal role in bringing producers and veterinarians together for the benefit of the industry. Examples of situations in which producers have decided to voluntarily share data for extended periods of time to support applied research and, ultimately, disease control in the absence of a regulatory framework have rarely been documented in the peer-reviewed literature. Here, we provide evidence of a national program for voluntary sharing of disease status data that has helped the implementation of surveillance activities that, ultimately, allowed the generation of critically important scientific information to better support disease control activities. Altogether, this effort has supported, and is supporting, the design and implementation of prevention and control approaches for the most economically devastating swine disease affecting the US. The program, which has been voluntarily sustained and supported over an extended period of time by the swine industry in the absence of any regulatory framework and that includes data on approximately 50% of the sow population in the US, represents a unique example of a livestock industry self-organized surveillance program to generate scientific-driven solutions for emerging swine health issues in North America.",2019 Jun 21,"['Perez, Andres M.', 'Linhares, Daniel C. L.', 'Arruda, Andreia G.', 'VanderWaal, Kimberly', 'Machado, Gustavo', 'Vilalta, Carles', 'Sanhueza, Juan M.', 'Torrison, Jerry', 'Torremorell, Montserrat', 'Corzo, Cesar A.']",Front Vet Sci,,,True
71f9800bec3740702f01d4658029642ad7e801f1,PMC,Conventional and Specific-Pathogen Free Rats Respond Differently to Anesthesia and Surgical Trauma,http://dx.doi.org/10.1038/s41598-019-45871-z,PMC6599031,31253875,CC BY,"Specific-pathogen free (SPF) animals were introduced in the 1960s to minimize disease and infection as variables in biomedical research. Our aim was to examine differences in physiological response in rat colonies bred and housed in a conventional versus SPF facility, and implications for research. Sprague-Dawley rats were anesthetized and catheterized for blood and pressure monitoring, and electrocardiogram (ECG) leads implanted. Hematology was assessed, and coagulation profile using rotational thromboelastometry. Health screening was outsourced to Cerberus Sciences. SPF rats had significantly lower pulse pressure (38% decrease), arrhythmias and prolonged QTc (27% increase) compared to conventional rats. No arrhythmias were found in conventional rats. SPF rats had significantly higher white cell, monocyte, neutrophil and lymphocyte counts, and were hyperfibrinolytic, indicated by EXTEM maximum lysis >15%. Independent assessment revealed similar pathogen exclusion between colonies, with the exception of Proteus in SPF animals. Returning to a conventional facility restored normal host physiology. We conclude that SPF animals displayed an abnormal hemodynamic, hematological and hemostatic phenotype in response to anesthesia and surgery, and provide a number of recommendations to help standardize research outcomes and translation.",2019 Jun 28,"['Letson, Hayley L.', 'Morris, Jodie', 'Biros, Erik', 'Dobson, Geoffrey P.']",Sci Rep,,,True
e78cecafd32aeadea4fe12d0a7d3f7883d222b58,PMC,Comparison of the immune response to vaccination with pigeon circovirus recombinant capsid protein (PiCV rCP) in pigeons uninfected and subclinically infected with PiCV,http://dx.doi.org/10.1371/journal.pone.0219175,PMC6599111,31251772,CC BY,"Infections with immunosuppressive pigeon circovirus (PiCV) pose the most severe health problem to the global pigeon breeding. The vaccination with immunogenic PiCV recombinant capsid protein (PiCV rCP) is a potential tool for disease control. Because of the high prevalence of PiCV asymptomatic infections, the subclinically infected pigeons will be vaccinated in practice. The aim of this study was to answer a question if vaccination of asymptomatic, infected with PiCV pigeons induces a similar immune response to PiCV rCP as in uninfected birds. One hundred and twenty 6-week-old carrier pigeons were divided into 4 groups (2 groups of naturally infected and uninfected with PiCV individuals). Birds from groups V and V1 were vaccinated twice with PiCV rCP mixed with an adjuvant, whereas pigeons from groups C and C1 were immunized with an adjuvant only. The expression of genes encoding IFN-γ, CD4, and CD8 T lymphocyte receptors; the number of anti-PiCV rCP IgY-secreting B cells (SBC) and anti-PiCV rCP IgY were evaluated 2, 21, 39 and 46 days post vaccination (dpv). Study results showed that the expression of CD8 and IFN-γ genes was higher in both groups of infected pigeons than in the uninfected birds, irrespective of vaccination. In the uninfected birds, the expression of these genes was insignificantly higher in the vaccinated pigeons. The anti-PiCV rCP IgY-SBC were detected on 2 and 23 dpv and seroconversion was noted on 23 and 39 dpv in V and V1 groups, respectively. In the light of the results obtained, it could be concluded that pigeon circovirus recombinant capsid protein elicits the immune response in both naturally infected and uninfected pigeons, but its rate varies depending on PiCV infectious status. The infection with PiCV masks the potential cellular immune response to the vaccination with PiCV rCP and leads to the suppression of humoral immunity.",2019 Jun 28,"['Stenzel, Tomasz', 'Dziewulska, Daria', 'Śmiałek, Marcin', 'Tykałowski, Bartłomiej', 'Kowalczyk, Joanna', 'Koncicki, Andrzej']",PLoS One,,,True
44a829b511efa9f170f4bc77446048fdc8a74d50,PMC,Evaluation of scrub typhus diagnosis in China: analysis of nationwide surveillance data from 2006 to 2016,http://dx.doi.org/10.1186/s40249-019-0566-0,PMC6599364,31253202,CC BY,"BACKGROUND: Scrub typhus is a life-threatening disease caused by Orientia tsutsugamushi, and specific antimicrobial medicine is available. Early and accurate diagnosis is essential for reducing the risk of severe complications and death. In this study, we aimed to evaluate the case diagnosis situation among medical care institutions and geographical regions in China, and the results will benefit both clinical practice and the disease surveillance system. METHODS: We extracted individual scrub typhus case data 2006–2016 from a national disease surveillance system in China. The diagnosis category and interval time from illness onset to diagnosis were compared among three levels of medical care institutions and provinces. The descriptive analysis method was performed in our study. RESULTS: During the 11-year study period, 93 481 scrub typhus cases, including 57 deaths, were recorded in the nationwide surveillance system. The overall proportion of laboratory-confirmed cases was only 4.7%, and this proportion varied greatly among primary medical centres (2.8%), county level hospitals (4.2%), and city level hospitals (6.3%). Notably, the proportion of laboratory-confirmed cases has consistently decreased from 16.3% in 2006 to 2.6% in 2016, and the same decreasing trend was found among all three levels of medical care institutions. The interval from illness onset to case diagnosis (T(diag)) for all cases was 5 days (interquartile range [IQR]: 2–9 days) and decreased from 7 days (IQR: 3–11 days) in 2006 to 5 days (IQR: 2–8 days) in 2016. The risk of death for patients with a T(diag) of > 7 days was 2.2 times higher (OR = 2.21, 95% CI: 1.05–5.21) than that of patients with a T(diag) of < 2 days. CONCLUSIONS: The interval time from illness onset to diagnosis for scrub typhus cases decreased greatly in China; however, the diagnosis rate of cases with laboratory-confirmed results must be increased among all levels of medical care institutions to reduce both the risk of death and the misuse of antibiotics associated with scrub typhus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-019-0566-0) contains supplementary material, which is available to authorized users.",2019 Jun 29,"['Xin, Hua-Lei', 'Yu, Jian-Xing', 'Hu, Mao-Gui', 'Jiang, Fa-Chun', 'Li, Xiao-Jing', 'Wang, Li-Ping', 'Huang, Ji-Lei', 'Wang, Jin-Feng', 'Sun, Jun-Ling', 'Li, Zhong-Jie']",Infect Dis Poverty,,,False
84a52dad0aab6d229fa21d15308819c3f792e539,PMC,Evaluation of scrub typhus diagnosis in China: analysis of nationwide surveillance data from 2006 to 2016,http://dx.doi.org/10.1186/s40249-019-0566-0,PMC6599364,31253202,CC BY,"BACKGROUND: Scrub typhus is a life-threatening disease caused by Orientia tsutsugamushi, and specific antimicrobial medicine is available. Early and accurate diagnosis is essential for reducing the risk of severe complications and death. In this study, we aimed to evaluate the case diagnosis situation among medical care institutions and geographical regions in China, and the results will benefit both clinical practice and the disease surveillance system. METHODS: We extracted individual scrub typhus case data 2006–2016 from a national disease surveillance system in China. The diagnosis category and interval time from illness onset to diagnosis were compared among three levels of medical care institutions and provinces. The descriptive analysis method was performed in our study. RESULTS: During the 11-year study period, 93 481 scrub typhus cases, including 57 deaths, were recorded in the nationwide surveillance system. The overall proportion of laboratory-confirmed cases was only 4.7%, and this proportion varied greatly among primary medical centres (2.8%), county level hospitals (4.2%), and city level hospitals (6.3%). Notably, the proportion of laboratory-confirmed cases has consistently decreased from 16.3% in 2006 to 2.6% in 2016, and the same decreasing trend was found among all three levels of medical care institutions. The interval from illness onset to case diagnosis (T(diag)) for all cases was 5 days (interquartile range [IQR]: 2–9 days) and decreased from 7 days (IQR: 3–11 days) in 2006 to 5 days (IQR: 2–8 days) in 2016. The risk of death for patients with a T(diag) of > 7 days was 2.2 times higher (OR = 2.21, 95% CI: 1.05–5.21) than that of patients with a T(diag) of < 2 days. CONCLUSIONS: The interval time from illness onset to diagnosis for scrub typhus cases decreased greatly in China; however, the diagnosis rate of cases with laboratory-confirmed results must be increased among all levels of medical care institutions to reduce both the risk of death and the misuse of antibiotics associated with scrub typhus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-019-0566-0) contains supplementary material, which is available to authorized users.",2019 Jun 29,"['Xin, Hua-Lei', 'Yu, Jian-Xing', 'Hu, Mao-Gui', 'Jiang, Fa-Chun', 'Li, Xiao-Jing', 'Wang, Li-Ping', 'Huang, Ji-Lei', 'Wang, Jin-Feng', 'Sun, Jun-Ling', 'Li, Zhong-Jie']",Infect Dis Poverty,,,True
65a49f91fda031c7e95543c2d73082b090d08ffc,PMC,Attenuation of Infectious Bronchitis Virus in Eggs Results in Different Patterns of Genomic Variation across Multiple Replicates,http://dx.doi.org/10.1128/JVI.00492-19,PMC6600199,31043525,CC BY,"The gammacoronavirus infectious bronchitis virus (IBV) causes an acute, highly contagious respiratory disease of poultry. Live attenuated vaccines are traditionally generated by serial passage of a virulent strain in embryonated chicken eggs; however, the molecular mechanism of attenuation is unknown. M41-CK, a virulent lab-adapted strain of IBV, was egg passaged over 100 times in four parallel independent replicates. All four final egg-passaged viruses were attenuated in vivo and exhibited similar growth phenotypes in adult chicken kidney cells and ex vivo tracheal organ cultures. The virus populations were sequenced by 454 pyrosequencing at the end of passaging, and the results showed that overall sequence diversity in the IBV population increased but the four replicates only had between 11 and 17 consensus-level single nucleotide polymorphisms (SNPs). Although hot spots of variation were identified in spike and nucleocapsid structural proteins as well as the 3ʹ untranslated region, each attenuated virus possessed a different pattern of genomic variation. Overall, only a small number of consensus-level SNPs were acquired during egg passage, leaving a potentially short route back to virulence. These results highlight the unpredictable nature of attenuation by serial egg passage and the need to develop mechanisms to rationally attenuate IBV for the next generation of effective vaccines. IMPORTANCE Infectious bronchitis remains a major problem in the global poultry industry, despite the existence of many different vaccines. IBV vaccines are currently developed by serial passage of a virulent strain on embryonated hen’s eggs until attenuation; however, little is known about the evolution of the viral population during the process of attenuation. High-throughput sequencing of four replicates of a serially egg-passaged IBV revealed a different pattern of genomic variation in each attenuated replicate and few consensus-level SNPs. This raises concerns that only a small number of genomic mutations are required to revert to a virulent phenotype, which may result in vaccine breakdown in the field. The observed hot spots of variation in the attenuated viruses have the potential to be used in the rational attenuation of virulent IBV for next-generation vaccine design.",2019 Jun 28,"['Oade, Michael S.', 'Keep, Sarah', 'Freimanis, Graham L.', 'Orton, Richard J.', 'Britton, Paul', 'Hammond, John A.', 'Bickerton, Erica']",J Virol,,,True
4dcde213ebf72aff0935b2714faf7fd691736c5e,PMC,"3′,8″-Dimerization Enhances the Antioxidant Capacity of Flavonoids: Evidence from Acacetin and Isoginkgetin",http://dx.doi.org/10.3390/molecules24112039,PMC6600363,31142008,CC BY,"To probe the effect of 3′,8″-dimerization on antioxidant flavonoids, acacetin and its 3′,8″-dimer isoginkgetin were comparatively analyzed using three antioxidant assays, namely, the ·O(2)(−) scavenging assay, the Cu(2+) reducing assay, and the 2,2′-azino bis(3-ethylbenzothiazolin-6-sulfonic acid) radical scavenging assay. In these assays, acacetin had consistently higher IC(50) values than isoginkgetin. Subsequently, the acacetin was incubated with 4-methoxy-2,2,6,6-tetramethylpiperidine-1-oxy radicals (4-methoxy-TEMPO) and then analyzed by ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC−ESI−Q−TOF−MS) technology. The results of the UHPLC−ESI−Q−TOF−MS analysis suggested the presence of a dimer with m/z 565, 550, 413, 389, 374, 345, 330, and 283 peaks. By comparison, standard isoginkgetin yielded peaks at m/z 565, 533, 518, 489, 401, 389, 374, and 151 in the mass spectra. Based on these experimental data, MS interpretation, and the relevant literature, we concluded that isoginkgetin had higher electron transfer potential than its monomer because of the 3′,8″-dimerization. Additionally, acacetin can produce a dimer during its antioxidant process; however, the dimer is not isoginkgetin.",2019 May 28,"['Li, Xican', 'Ouyang, Xiaojian', 'Cai, Rongxin', 'Chen, Dongfeng']",Molecules,,,True
ab9e34ee687f60a4de8ef675f307230e1b6c6f23,PMC,HBV Immune-Therapy: From Molecular Mechanisms to Clinical Applications,http://dx.doi.org/10.3390/ijms20112754,PMC6600394,31195619,CC BY,"Chronic hepatitis B virus (HBV) infection represents a worldwide public health concern with approximately 250 million people chronically infected and at risk of developing liver cirrhosis and hepatocellular carcinoma. Nucleos(t)ide analogues (NUC) are the most widely used therapies for HBV infection, but they often require long-lasting administration to avoid the risk of HBV reactivation at withdrawal. Therefore, there is an urgent need to develop novel treatments to shorten the duration of NUC therapy by accelerating virus control, and to complement the effect of available anti-viral therapies. In chronic HBV infection, virus-specific T cells are functionally defective, and this exhaustion state is a key determinant of virus persistence. Reconstitution of an efficient anti-viral T cell response may thus represent a rational strategy to treat chronic HBV patients. In this perspective, the enhancement of adaptive immune responses by a checkpoint inhibitor blockade, specific T cell vaccines, lymphocyte metabolism targeting, and autologous T cell engineering, including chimeric antigen receptor (CAR) and TCR-redirected T cells, constitutes a promising immune modulatory approach for a therapeutic restoration of protective immunity. The advances of the emerging immune-based therapies in the setting of the HBV research field will be outlined.",2019 Jun 5,"['Boni, Carolina', 'Barili, Valeria', 'Acerbi, Greta', 'Rossi, Marzia', 'Vecchi, Andrea', 'Laccabue, Diletta', 'Penna, Amalia', 'Missale, Gabriele', 'Ferrari, Carlo', 'Fisicaro, Paola']",Int J Mol Sci,,,True
fe21f4cd051907ab122c5583ca3d95ccaacba508,PMC,Resiquimod-Mediated Activation of Plasmacytoid Dendritic Cells Is Amplified in Multiple Sclerosis,http://dx.doi.org/10.3390/ijms20112811,PMC6600519,31181776,CC BY,"Background: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. The cause of multiple sclerosis is unknown but there are several evidences that associate the genetic basis of the disease with environmental causes. An important association between viral infection and development of MS is clearly demonstrated. Viruses have a strong impact on innate immune cells. In particular, myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs), are able to respond to viruses and to activate the adaptive immune response. Methods: In this study we mimic viral infection using synthetic single-strand RNA, Resiquimod, and we compared the response of both DC subsets derived from healthy donors and MS patients by characterizing the expression of costimulatory molecules on the DC surface. Results: We found that pDCs from MS patients express higher levels of OX40-L, HLA-DR, and CD86 than healthy donors. Moreover, we found that blood cells from MS patients and healthy donors upon Resiquimod-stimulation are enriched in a subpopulation of pDCs, characterized by a high amount of costimulatory molecules. Conclusion: Overall, these results indicate that activation of pDCs is enhanced in MS, likely due to a latent viral infection, and that costimulatory molecules expressed on pDCs could mediate a protective response against the viral trigger of autoimmunity.",2019 Jun 8,"['Corsetti, Marta', 'Ruocco, Gabriella', 'Ruggieri, Serena', 'Gasperini, Claudio', 'Battistini, Luca', 'Volpe, Elisabetta']",Int J Mol Sci,,,True
2ed23e6fe433d2ce14436eaa68a9ab6240a00500,PMC,Cross-Species Genome-Wide Analysis Reveals Molecular and Functional Diversity of the Unconventional Interferon-ω Subtype,http://dx.doi.org/10.3389/fimmu.2019.01431,PMC6603160,31293589,CC BY,"Innate immune interferons (IFNs), particularly type I IFNs, are primary mediators regulating animal antiviral, antitumor, and cell-proliferative activity. These antiviral cytokines have evolved remarkable molecular and functional diversity to confront ever-evolving viral threats and physiological regulation. We have annotated IFN gene families across 110 animal genomes, and showed that IFN genes, after originating in jawed fishes, had several significant evolutionary surges in vertebrate species of amphibians, bats and ungulates, particularly pigs and cattle. For example, pigs have the largest but still expanding type I IFN family consisting of nearly 60 IFN-coding genes that encode seven IFN subtypes including multigene subtypes of IFN-α, -δ, and -ω. Whereas, subtypes such as IFN-α and -β have been widely studied in many species, the unconventional subtypes such as IFN-ω have barely been investigated. We have cross-species defined the IFN evolution, and shown that unconventional IFN subtypes particularly the IFN-ω subtype have evolved several novel features including: (1) being a signature multi-gene subtype expanding primarily in mammals such as bats and ungulates, (2) emerging isoforms that have superior antiviral potency than typical IFN-α, (3) highly cross-species antiviral (but little anti-proliferative) activity exerted in cells of humans and other mammalian species, and (4) demonstrating potential novel molecular and functional properties. This study focused on IFN-ω to investigate the immunogenetic evolution and functional diversity of unconventional IFN subtypes, which may further IFN-based novel antiviral design pertinent to their cross-species high antiviral and novel activities.",2019 Jun 25,"['Shields, Lauren E.', 'Jennings, Jordan', 'Liu, Qinfang', 'Lee, Jinhwa', 'Ma, Wenjun', 'Blecha, Frank', 'Miller, Laura C.', 'Sang, Yongming']",Front Immunol,,,True
4ce5891928816eb6068228ce463b91ed70df44e1,PMC,Examining the Complex Relationship Between Tuberculosis and Other Infectious Diseases in Children,http://dx.doi.org/10.3389/fped.2019.00233,PMC6603259,31294001,CC BY,"Millions of children are exposed to tuberculosis (TB) each year, many of which become infected with Mycobacterium tuberculosis. Most children can immunologically contain or eradicate the organism without pathology developing. However, in a minority, the organism overcomes the immunological constraints, proliferates and causes TB disease. Each year a million children develop TB disease, with a quarter dying. While it is known that young children and those with immunodeficiencies are at increased risk of progression from TB infection to TB disease, our understanding of risk factors for this transition is limited. The most immunologically disruptive process that can happen during childhood is infection with another pathogen and yet the impact of co-infections on TB risk is poorly investigated. Many diseases have overlapping geographical distributions to TB and affect similar patient populations. It is therefore likely that infection with viruses, bacteria, fungi and protozoa may impact on the risk of developing TB disease following exposure and infection, although disentangling correlation and causation is challenging. As vaccinations also disrupt immunological pathways, these may also impact on TB risk. In this article we describe the pediatric immune response to M. tuberculosis and then review the existing evidence of the impact of co-infection with other pathogens, as well as vaccination, on the host response to M. tuberculosis. We focus on the impact of other organisms on the risk of TB disease in children, in particularly evaluating if co-infections drive host immune responses in an age-dependent way. We finally propose priorities for future research in this field. An improved understanding of the impact of co-infections on TB could assist in TB control strategies, vaccine development (for TB vaccines or vaccines for other organisms), TB treatment approaches and TB diagnostics.",2019 Jun 25,"['Whittaker, Elizabeth', 'López-Varela, Elisa', 'Broderick, Claire', 'Seddon, James A.']",Front Pediatr,,,True
4261cfd373572b30e170171afce095e6eb5d806a,PMC,Severe Morbidity and Mortality Associated With Respiratory Syncytial Virus Versus Influenza Infection in Hospitalized Older Adults,http://dx.doi.org/10.1093/cid/ciy991,PMC6603263,30452608,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of serious respiratory illness in older adults. Comparison of RSV and influenza infection in hospitalized older adults may increase awareness of adult RSV disease burden. METHODS: Hospitalized adults aged ≥60 years who tested positive for RSV or influenza between 1 January 2011 and 30 June 2015 were identified from Kaiser Permanente Southern California electronic medical records. Baseline characteristics, comorbidities, utilization, and outcomes were compared. RESULTS: The study included 645 RSV- and 1878 influenza-infected hospitalized adults. Patients with RSV were older than those with influenza (mean, 78.5 vs 77.4 years; P = .035) and more likely to have congestive heart failure (35.3% vs 24.5%; P < .001) and chronic obstructive pulmonary disease (COPD) (29.8% vs 24.3%; P = .006) at baseline. In adjusted analyses, RSV infection was associated with greater odds of length of stay ≥7 days (odds ratio [OR] = 1.5; 95% confidence interval [CI], 1.2–1.8; P < .001); pneumonia (OR = 2.7; 95% CI, 2.2–3.2; P < .001); intensive care unit admission (OR = 1.3; 95% CI, 1.0–1.7; P = .023); exacerbation of COPD (OR = 1.7; 95% CI, 1.3–2.4; P = .001); and greater mortality within 1 year of admission (OR = 1.3; 95% CI, 1.0–1.6; P = .019). CONCLUSIONS: RSV infection may result in greater morbidity and mortality among older hospitalized adults than influenza. Increased recognition of adult RSV disease burden will be important in the evaluation and use of new RSV vaccines and antivirals.",2019 Jul 15,"['Ackerson, Bradley', 'Tseng, Hung Fu', 'Sy, Lina S', 'Solano, Zendi', 'Slezak, Jeff', 'Luo, Yi', 'Fischetti, Christine A', 'Shinde, Vivek']",Clin Infect Dis,,,True
55bf861b16d4b28c89750602b96b3827bdaf0055,PMC,Development and evaluation of recombinase-aided amplification assays incorporating competitive internal controls for detection of human adenovirus serotypes 3 and 7,http://dx.doi.org/10.1186/s12985-019-1178-9,PMC6604330,31262315,CC BY,"BACKGROUND: Human adenoviruses are a common group of viruses that cause acute infectious diseases. Human adenovirus (HAdV) 3 and HAdV 7 cause major outbreaks of severe pneumonia. A reliable and practical method for HAdV typing in clinical laboratories is lacking. A simple, rapid and accurate molecular typing method for HAdV may facilitate clinical diagnosis and epidemiological control. METHODS: We developed and evaluated duplex real-time recombinase-aided amplification (RAA) assays incorporating competitive internal controls for detection of HAdV 3 and HAdV 7, respectively. The assays were performed in a one-step in a single tube reaction at 39° for 20 min. RESULTS: The analytical sensitivities of the duplex RAA assays for HAdV 3 and HAdV 7 were 5.0 and 14.8 copies per reaction, respectively (at 95% probability by probit regression analysis). No cross-reaction was observed with other types of HAdV or other common respiratory viruses. The duplex RAA assays were used to detect 152 previously-defined HAdV-positive samples. These results agreed with those obtained using a published triplex quantitative real-time PCR protocol. CONCLUSIONS: We provide the first report of internally-controlled duplex RAA assays for the detection of HAdV 3 and HAdV 7. These assays effectively reduce the rate of false negative results and may be valuable for detection of HAdV 3 and HAdV 7 in clinical laboratories, especially in resource-poor settings.",2019 Jul 1,"['Wang, Rui-huan', 'Zhang, Hong', 'Zhang, Yi', 'Li, Xin-na', 'Shen, Xin-xin', 'Qi, Ju-ju', 'Fan, Guo-hao', 'Xiang, Xing-yu', 'Zhan, Zhi-fei', 'Chen, Zi-wei', 'Ma, Xue-jun']",Virol J,,,True
1582cbf653a14f9033c7a33567909f54e736ba6e,PMC,Risk Attitudes Affect Livestock Biosecurity Decisions With Ramifications for Disease Control in a Simulated Production System,http://dx.doi.org/10.3389/fvets.2019.00196,PMC6604760,31294037,CC BY,"Hog producers' operational decisions can be informed by an awareness of risks associated with emergent and endemic diseases. Outbreaks of porcine epidemic diarrhea virus (PEDv) have been re-occurring every year since the first onset in 2013 with substantial losses across the hog production supply chain. Interestingly, a decreasing trend in PEDv incidence is visible. We assert that changes in human behaviors may underlie this trend. Disease prevention using biosecurity practices is used to minimize risk of infection but its efficacy is conditional on human behavior and risk attitude. Standard epidemiological models bring important insights into disease dynamics but have limited predictive ability. Since research shows that human behavior plays a driving role in the disease spread process, the explicit inclusion of human behavior into models adds an important dimension to understanding disease spread. Here we analyze PEDv incidence emerging from an agent-based model (ABM) that uses both epidemiological dynamics and algorithms that incorporate heterogeneous human decisions. We investigate the effects of shifting fractions of hog producers between risk tolerant and risk averse positions. These shifts affect the dynamics describing willingness to increase biosecurity as a response to disease threats and, indirectly, change infection probabilities and the resultant intensity and impact of the disease outbreak. Our ABM generates empirically verifiable patterns of PEDv transmission. Scenario results show that relatively small shifts (10% of the producer agents) toward a risk averse position can lead to a significant decrease in total incidence. For significantly steeper decreases in disease incidence, the model's hog producer population needed at least 37.5% of risk averse. Our study provides insight into the link between risk attitude, decisions related to biosecurity, and consequent spread of disease within a livestock production system. We suggest that it is possible to create positive, lasting changes in animal health by nudging the population of livestock producers toward more risk averse behaviors. We make a case for integrating social and epidemiological aspects in disease spread models to test intervention strategies intended to improve biosecurity and animal health at the system scale.",2019 Jun 25,"['Bucini, Gabriela', 'Merrill, Scott C.', 'Clark, Eric', 'Moegenburg, Susan M.', 'Zia, Asim', 'Koliba, Christopher J.', 'Wiltshire, Serge', 'Trinity, Luke', 'Smith, Julia M.']",Front Vet Sci,,,False
6b76a747ec773a8604c95aa082bbb51fd95af353,PMC,Risk Attitudes Affect Livestock Biosecurity Decisions With Ramifications for Disease Control in a Simulated Production System,http://dx.doi.org/10.3389/fvets.2019.00196,PMC6604760,31294037,CC BY,"Hog producers' operational decisions can be informed by an awareness of risks associated with emergent and endemic diseases. Outbreaks of porcine epidemic diarrhea virus (PEDv) have been re-occurring every year since the first onset in 2013 with substantial losses across the hog production supply chain. Interestingly, a decreasing trend in PEDv incidence is visible. We assert that changes in human behaviors may underlie this trend. Disease prevention using biosecurity practices is used to minimize risk of infection but its efficacy is conditional on human behavior and risk attitude. Standard epidemiological models bring important insights into disease dynamics but have limited predictive ability. Since research shows that human behavior plays a driving role in the disease spread process, the explicit inclusion of human behavior into models adds an important dimension to understanding disease spread. Here we analyze PEDv incidence emerging from an agent-based model (ABM) that uses both epidemiological dynamics and algorithms that incorporate heterogeneous human decisions. We investigate the effects of shifting fractions of hog producers between risk tolerant and risk averse positions. These shifts affect the dynamics describing willingness to increase biosecurity as a response to disease threats and, indirectly, change infection probabilities and the resultant intensity and impact of the disease outbreak. Our ABM generates empirically verifiable patterns of PEDv transmission. Scenario results show that relatively small shifts (10% of the producer agents) toward a risk averse position can lead to a significant decrease in total incidence. For significantly steeper decreases in disease incidence, the model's hog producer population needed at least 37.5% of risk averse. Our study provides insight into the link between risk attitude, decisions related to biosecurity, and consequent spread of disease within a livestock production system. We suggest that it is possible to create positive, lasting changes in animal health by nudging the population of livestock producers toward more risk averse behaviors. We make a case for integrating social and epidemiological aspects in disease spread models to test intervention strategies intended to improve biosecurity and animal health at the system scale.",2019 Jun 25,"['Bucini, Gabriela', 'Merrill, Scott C.', 'Clark, Eric', 'Moegenburg, Susan M.', 'Zia, Asim', 'Koliba, Christopher J.', 'Wiltshire, Serge', 'Trinity, Luke', 'Smith, Julia M.']",Front Vet Sci,,,True
d4c6f970018efbcc9df15a758f7ff2396f33225e,PMC,Successful Treatment of Legionnaires’ Disease with Tigecycline in an Immunocompromised Man with a Legion of Antibiotic Allergies,http://dx.doi.org/10.7759/cureus.4577,PMC6605692,31281760,CC BY,"Legionella species are Gram-negative bacilli that are relatively rare causes of community-acquired pneumonia but can be associated with significant morbidity and mortality if unrecognized or improperly treated. Limited data exist regarding the use of tigecycline, a third generation glycylcycline, in the treatment of Legionnaires' disease. We present an immunocompromised patient with Legionnaires' disease and allergies to both fluoroquinolones and macrolides, which are first-line treatment options for Legionnaires' disease. He was successfully treated using tigecycline, a third generation glycylcycline, indicating that tigecycline may serve as a safe and effective alternative therapeuticl option for treatment of Legionnaires’ disease.",,"['Arget, Michael', 'Kosar, Justin', 'Suen, Brandon', 'Peermohamed, Shaqil']",Cureus.; 11(4):e4577,,,True
8e6ef0f551beb549a3e0d523f5b1472cd11110f4,PMC,A novel group of avian astroviruses from Neotropical passerine birds broaden the diversity and host range of Astroviridae,http://dx.doi.org/10.1038/s41598-019-45889-3,PMC6606752,31266971,CC BY,"Metagenomics is helping to expand the known diversity of viruses, especially of those with poorly studied hosts in remote areas. The Neotropical region harbors a considerable diversity of avian species that may play a role as both host and short-distance vectors of unknown viruses. Viral metagenomics of cloacal swabs from 50 Neotropical birds collected in French Guiana revealed the presence of four complete astrovirus genomes. They constitute an early diverging novel monophyletic clade within the Avastrovirus phylogeny, representing a putative new astrovirus species (provisionally designated as Avastrovirus 5) according to the International Committee on Taxonomy of Viruses (ICTV) classification criteria. Their genomic organization shares some characteristics with Avastrovirus but also with Mamastrovirus. The pan-astrovirus RT-PCR analysis of the cloacal samples of 406 wild Neotropical birds showed a community-level prevalence of 4.9% (5.1% in passerines, the highest described so far in this order of birds). By screening birds of a remote region, we expanded the known host range of astroviruses to the avian families Cardinalidae, Conopophagidae, Furnariidae, Thamnophilidae, Turdidae and Tyrannidae. Our results provide important first insights into the unexplored viral communities, the ecology, epidemiology and features of host-pathogen interactions that shape the evolution of avastroviruses in a remote Neotropical rainforest.",2019 Jul 2,"['Fernández-Correa, Izaskun', 'Truchado, Daniel A.', 'Gomez-Lucia, Esperanza', 'Doménech, Ana', 'Pérez-Tris, Javier', 'Schmidt-Chanasit, Jonas', 'Cadar, Daniel', 'Benítez, Laura']",Sci Rep,,,True
44dd2bffc40a5e211d8a9c2b080b93570671d703,PMC,China's Response to the 2014 Ebola Outbreak in West Africa,http://dx.doi.org/10.1002/gch2.201600001,PMC6607196,31565261,CC BY,"Beginning in March 2014, West Africa has endured the largest outbreak of Ebola viral disease (EVD) in history. The crisis highlighted the role of China in addressing public health emergencies of international concern (PHEIC). Through bilateral and multilateral channels, China kicked off its largest ever humanitarian mission in addressing a PHEIC. The unprecedented generosity served the domestic needs to prevent EVD from spreading into China, but it was also consistent with China's foreign policy objective to pursue soft power in Africa. While its total funding to EVD control in West Africa was no match of top donors like the United States, it becomes much more impressive when adjusted for gross domestic product (GDP) per capita. As Beijing becomes more sensitive to disease outbreaks overseas and as the scope of its humanitarian engagement grows and diversifies, the space for China's cooperation with international actors over global health governance is expected to further expand.",2017 Jan 30,"Huang, Yanzhong",Glob Chall,,,True
60cd8a2169f79423f22c91678fc76cf5bb216ef5,PMC,T cell-selective deletion of Oct1 protects animals from autoimmune neuroinflammation while maintaining neurotropic pathogen response,http://dx.doi.org/10.1186/s12974-019-1523-3,PMC6607600,31266507,CC BY,"BACKGROUND: Treatments for autoimmune diseases aim to dampen autoreactivity while preserving normal immune function. In CD4(+) T cells, the transcription factor Oct1/Pou2f1 is a dispensable transcription factor for T cell development and response to primary infection, but promotes expression of target genes, including Il2 and Ifng, under conditions of antigen reencounter. As a result, they are more strongly expressed upon secondary stimulation. Such repeated antigen encounters occur in memory recall responses, in autoimmunity where self-antigen can be recognized multiple times, and in chronic infection where foreign antigen is persistent. Based on these previous findings, we hypothesized that Oct1 loss would protect animals from autoimmunity but maintain normal responses to pathogens in the CNS. OBJECTIVE: We used a conditional mouse Oct1 (Pou2f1) allele and a CD4-Cre driver to determine the effect of T cell-specific Oct1 loss on autoimmune- and viral-induced neuroinflammation using an autoantigen-driven EAE model of autoimmunity and a JHMV model of viral infection. RESULTS: Oct1 conditional deletion mitigated clinical scores and reduced infiltrating T cells and cytokine production in the EAE model. Consistently, Oct1-deficient CD4(+) T cells stimulated in vitro showed increased expression of markers associated with T cell anergy, particularly in the absence of co-stimulatory signals. In contrast, anti-viral T cell effector functions are intact in the absence of Oct1, with no changes in neuroinflammation, infiltrating T cells or cytokine production. CONCLUSION: Our findings uncover a significant difference between the effect of Oct1 loss on autoimmune and anti-pathogen responses, which potentially could be exploited for therapeutic benefit. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-019-1523-3) contains supplementary material, which is available to authorized users.",2019 Jul 3,"['Kim, Heejoo', 'Dickey, Laura', 'Stone, Colleen', 'Jafek, Jillian L.', 'Lane, Thomas E.', 'Tantin, Dean']",J Neuroinflammation,,,True
b39cfc766778529c14cb69cc1b12e016fb9581d0,PMC,Frequent detection of Saffold cardiovirus in adenoids,http://dx.doi.org/10.1371/journal.pone.0218873,PMC6608973,31269055,CC BY,"Saffold virus (SAFV) is classified into the Cardiovirus genus of the Picornaviridae family. Up to now, eleven genotypes have been identified however, their clinical significance remains unclear. Here, we investigated the presence of SAFV in asymptomatic patients admitted for adenoidectomy. A total of 70 adenoid tissue samples were collected from children with clinical symptoms caused by hypertrophy of adenoids but without symptoms of airway infection. Samples were investigated for SAFV by RT-nested PCR and sequence analysis. Eleven of 70 (15.7%) samples were positive for SAFV. Nasopharyngeal swabs were available from 45 children just before surgery. SAFV was rarely found and only in children with SAFV-positive adenoids 2/8. Our findings indicate that the presence of SAFV seems to be more frequent in adenoid tissue than expected. This could support the notion of a longer than previously anticipated persistence of SAFV nucleic acids in the respiratory tract and possibly a chronic infection. Further investigations are necessary to establish the role of SAFV infection in humans.",2019 Jul 3,"['Lindner, Kira', 'Ludwig, Michael', 'Bootz, Friedrich', 'Reber, Ulrike', 'Safavieh, Zahrasadat', 'Eis-Hübinger, Anna Maria', 'Herberhold, Stephan']",PLoS One,,,True
5bb58fba5bb25b55cc4bcb4e229ba2d196b4bc99,PMC,Global analysis of polysome-associated mRNA in vesicular stomatitis virus infected cells,http://dx.doi.org/10.1371/journal.ppat.1007875,PMC6608984,31226162,CC BY,"Infection of mammalian cells with vesicular stomatitis virus (VSV) results in the inhibition of cellular translation while viral translation proceeds efficiently. VSV RNA synthesis occurs entirely within the cytoplasm, where during transcription the viral polymerase produces 5 mRNAs that are structurally indistinct to cellular mRNAs with respect to their 5′ cap-structure and 3′-polyadenylate tail. Using the global approach of massively parallel sequencing of total cytoplasmic, monosome- and polysome-associated mRNA, we interrogate the impact of VSV infection of HeLa cells on translation. Analysis of sequence reads in the different fractions shows >60% of total cytoplasmic and polysome-associated reads map to the 5 viral genes by 6 hours post-infection, a time point at which robust host cell translational shut-off is observed. Consistent with an overwhelming abundance of viral mRNA in the polysome fraction, the reads mapping to cellular genes were reduced. The cellular mRNAs that remain most polysome-associated following infection had longer half-lives, were typically larger, and were more AU rich, features that are shared with the viral mRNAs. Several of those mRNAs encode proteins known to positively affect viral replication, and using chemical inhibition and siRNA depletion we confirm that the host chaperone heat shock protein 90 (hsp90) and eukaryotic translation initiation factor 3A (eIF3A)—encoded by 2 such mRNAs—support viral replication. Correspondingly, regulated in development and DNA damage 1 (Redd1) encoded by a host mRNA with reduced polysome association inhibits viral infection. These data underscore the importance of viral mRNA abundance in the shut-off of host translation in VSV infected cells and link the differential translatability of some cellular mRNAs with pro- or antiviral function.",2019 Jun 21,"['Neidermyer, William J.', 'Whelan, Sean P. J.']",PLoS Pathog,,,True
5719934f2cd95ffe4bd1aec0b7b9a314481aab60,PMC,The interleukin-4/PPARγ signaling axis promotes oligodendrocyte differentiation and remyelination after brain injury,http://dx.doi.org/10.1371/journal.pbio.3000330,PMC6608986,31226122,CC BY,"The repair of white matter damage is of paramount importance for functional recovery after brain injuries. Here, we report that interleukin-4 (IL-4) promotes oligodendrocyte regeneration and remyelination. IL-4 receptor expression was detected in a variety of glial cells after ischemic brain injury, including oligodendrocyte lineage cells. IL-4 deficiency in knockout mice resulted in greater deterioration of white matter over 14 d after stroke. Consistent with these findings, intranasal delivery of IL-4 nanoparticles after stroke improved white matter integrity and attenuated long-term sensorimotor and cognitive deficits in wild-type mice, as revealed by histological immunostaining, electron microscopy, diffusion tensor imaging, and electrophysiology. The selective effect of IL-4 on remyelination was verified in an ex vivo organotypic model of demyelination. By leveraging primary oligodendrocyte progenitor cells (OPCs), microglia-depleted mice, and conditional OPC-specific peroxisome proliferator-activated receptor gamma (PPARγ) knockout mice, we discovered a direct salutary effect of IL-4 on oligodendrocyte differentiation that was mediated by the PPARγ axis. Our findings reveal a new regenerative role of IL-4 in the central nervous system (CNS), which lies beyond its known immunoregulatory functions on microglia/macrophages or peripheral lymphocytes. Therefore, intranasal IL-4 delivery may represent a novel therapeutic strategy to improve white matter integrity in stroke and other brain injuries.",2019 Jun 21,"['Zhang, Qingxiu', 'Zhu, Wen', 'Xu, Fei', 'Dai, Xuejiao', 'Shi, Ligen', 'Cai, Wei', 'Mu, Hongfeng', 'Hitchens, T. Kevin', 'Foley, Lesley M.', 'Liu, Xiangrong', 'Yu, Fang', 'Chen, Jie', 'Shi, Yejie', 'Leak, Rehana K.', 'Gao, Yanqin', 'Chen, Jun', 'Hu, Xiaoming']",PLoS Biol,,,True
ff09007b2973bf3dc9a0435228a1b220587763da,PMC,Emerging Trends in Clinical Tropical Medicine Research,http://dx.doi.org/10.4269/ajtmh.19-0043,PMC6609189,31094312,CC BY,"The American Society for Tropical Medicine and Hygiene recently inaugurated an award for the best clinical research article published in the society’s journal in the previous year. This article summarizes both the process of selecting the winner and several themes that stood out in those articles which rose to the top for consideration. Themes of note included the importance of doing clinical research outside of referral centers, the complexity that must be considered when implementing interventions, incorporation of both ends of the age spectrum into studies, and considering cost-effectiveness and opportunity cost of interventions.",2019 Jul 13,"['Huntington, Mark K.', 'Bryan, Joe P.', 'Moon, Troy D.', 'Imperato, Pascal J.', 'McLellan, Susan L. F.', 'Taylor, Walter R.', 'Schieffelin, John S.']",Am J Trop Med Hyg,,,True
de5427785ad1385b62f0fbf18af129dc8cff303f,PMC,"Island blues: indigenous knowledge of indigo-yielding plant species used by Hainan Miao and Li dyers on Hainan Island, China",http://dx.doi.org/10.1186/s13002-019-0314-3,PMC6609400,31269961,CC BY,"BACKGROUND: Historically, indigo-yielding plant species were important cash crops from Central Asia to the southern United States and Central America. Indigo-dyed textiles were widely traded along the legendary Silk Road that linked China to Europe. Today, due to the labor-intensive nature of indigo extraction at the household level, lifestyle changes and the widespread availability of commercially produced indigo paste, traditional indigo extraction methods have declined in villages. Yet Li textile weavers on Hainan Island are internationally recognized as producers of indigo-dyed textile using warp ikat techniques. In contrast, Hainan Miao weavers produce indigo-dyed textiles using batik (wax resist) techniques. The aim of this study was to document the indigenous knowledge on indigo-yielding plant species used by both Hainan Miao and Li people on Hainan Island, China. METHOD: Ethnic uses were documented during three field surveys, through a questionnaire survey of 193 respondents, comprising 144 Hainan Miao and 49 Li traditional dyers. Mention index (QI), Availability index (AI), and Preference ranking (PR) of each indigo-yielding plant species were calculated to screen out plant resources with potential development value. RESULTS: Five indigo-yielding plant species (from four plant families and four genera) were historically used by Hainan Miao and Li dyers. However, just four species are still in use. Strobilanthes cusia was the main indigo source for Hainan Miao dyers. Li dyers also commonly use Indigofera species (I. tinctoria and I. suffruticosa) for indigo extraction. Wrightia laevis is less commonly used as a contemporary indigo source. Indigo extraction by steeping in water to which lime is added to increase the pH is sharing by the five indigo-yielding plant species. Strobilanthes cusia had the highest QI, AI and PR values in Hainan Miao villages. Indigofera tinctoria had the highest QI and AI values, but Indigofera suffruticosa was preferred by Li dyers. CONCLUSION: In the process of modernization and urbanization, some Hainan Miao and Li dyers retain the traditional indigo extraction methods. We found that Strobilanthes cusia and Indigofera tinctoria have the most potential for sustainable indigo production in the future. Furthermore, this study documents the details of extraction method from Wrightia laevis for the first time and the use of Ricinus communis seeds in that process. As one of the last places globally where Wrightia laevis is still used for indigo production, the may also be a nice market among textile collectors and museums that keeps the tradition of Wrightia laevis production and use for indigo extraction alive.",2019 Jul 3,"['Zhang, Libin', 'Wang, Lu', 'Cunningham, Anthony B.', 'Shi, Yuru', 'Wang, Yuhua']",J Ethnobiol Ethnomed,,,True
eaa61130ab5e4b11c8b104c76dfa4b56f496fb49,PMC,"Street-level diplomacy and local enforcement for meat safety in northern Tanzania: knowledge, pragmatism and trust",http://dx.doi.org/10.1186/s12889-019-7067-8,PMC6610827,31269927,CC BY,"BACKGROUND: With increasing demand for red meat in Tanzania comes heightened potential for zoonotic infections in animals and humans that disproportionately affect poor communities. A range of frontline government employees work to protect public health, providing services for people engaged in animal-based livelihoods (livestock owners and butchers), and enforcing meat safety and food premises standards. In contrast to literature which emphasises the inadequacy of extension support and food safety policy implementation in low- and middle-income countries, this paper foregrounds the ‘street-level diplomacy’ deployed by frontline actors operating in challenging contexts. METHODS: This research is based on semi-structured interviews with 61 government employees, including livestock extension officers/meat inspectors and health officers, across 10 randomly-selected rural and urban wards. RESULTS: Frontline actors combined formal and informal strategies including the leveraging of formal policy texts and relationships with other state employees, remaining flexible and recognising that poverty constrained people’s ability to comply with health regulations. They emphasised the need to work with livestock keepers and butchers to build their knowledge to self-regulate and to work collaboratively to ensure meat safety. Remaining adaptive and being hesitant to act punitively unless absolutely necessary cultivated trust and positive relations, making those engaged in animal-based livelihoods more open to learning from and cooperating with extension officers and inspectors. This may result in higher levels of meat safety than might be the case if frontline actors stringently enforced regulations. CONCLUSION: The current tendency to view frontline actors’ partial enforcement of meat safety regulations as a failure obscures the creative and proactive ways in which they seek to ensure meat safety in a context of limited resources. Their application of ‘street-level diplomacy’ enables them to be sensitive to local socio-economic realities, to respect local social norms and expectations and to build support for health safety interventions when necessary. More explicitly acknowledging the role of trust and positive state-society relations and the diplomatic skills deployed by frontline actors as a formal part of their inspection duties offers new perspectives and enhanced understandings on the complicated nature of their work and what might be done to support them. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-019-7067-8) contains supplementary material, which is available to authorized users.",2019 Jul 3,"['Hrynick, T. A.', 'Barasa, V.', 'Benschop, J.', 'Cleaveland, S.', 'Crump, J. A.', 'Davis, M.', 'Mariki, B.', 'Mmbaga, B. T.', 'Mtui-Malamsha, N.', 'Prinsen, G.', 'Sharp, J.', 'Sindiyo, E.', 'Swai, E. S.', 'Thomas, K. M.', 'Zadoks, R.', 'Waldman, L.']",BMC Public Health,,,True
c92fafbeda15f8604281f06c7461dcec5288d303,PMC,Aetiological Significance of Infectious Stimuli in Kawasaki Disease,http://dx.doi.org/10.3389/fped.2019.00244,PMC6611380,31316950,CC BY,"Kawasaki disease (KD) is a pediatric vasculitis syndrome that is often involves coronary artery lesions (e. g., coronary artery aneurysms). Although its causal factors and entire pathogenesis remain elusive, the available evidence indicates that the pathogenesis of KD is closely associated with dysregulation of immune responses to various viruses or microbes. In this short review, we address several essential aspects of the etiology of KD with respect to the immune response to infectious stimuli: 1) the role of viral infections, 2) the role of bacterial infections and the superantigen hypothesis, 3) involvement of innate immune response including pathogens/microbe-associated molecular patterns and complement pathways, and 4) the influence of genetic background on the response to infectious stimuli. Based on the clinical and experimental evidence, we discuss the possibility that a wide range of microbes and viruses could cause KD through common and distinct immune processes.",2019 Jun 28,"['Nakamura, Akihiro', 'Ikeda, Kazuyuki', 'Hamaoka, Kenji']",Front Pediatr,,,True
089acb4677633e0cf2d35fd728e686c8aa887bc0,PMC,An exploration of conditions proposed to trigger the Ebola virus glycoprotein for fusion,http://dx.doi.org/10.1371/journal.pone.0219312,PMC6611598,31276481,CC BY,"Ebolaviruses continue to inflict horrific disease and instill fear. The 2013–2016 outbreak in Western Africa caused unfathomable morbidity and mortality (over 11,000 deaths), and the second largest outbreak is on-going in the Democratic Republic of the Congo. The first stage of an Ebolavirus infection is entry, culminating in delivery of the viral genome into the cytoplasm to initiate replication. Among enveloped viruses, Ebolaviruses use a complex entry pathway: they bind to attachment factors on cell surfaces, are engulfed by macropinocytosis, and traffic through the endosomal system. En route, the receptor binding subunit of the glycoprotein (GP) is reduced from ~130 to ~19 kDa by cathepsins. This event allows cleaved GP (GP(cl)) to bind to Niemann-Pick C1 (NPC1), its endosomal receptor. The virus then fuses with a late endosomal membrane, but how this occurs remains a subject of debate. An early, but standing, observation is that entry of particles bearing GP(cl) is inhibited by agents that raise endosomal pH or inhibit cysteine proteases, suggesting the need for an additional factor(s). Yet, some have concluded that NPC1 is sufficient to trigger the fusion activity of GP(cl). Here, we re-examined this question using sensitive cell-cell and pseudovirus-cell fusion assays. We did not observe detectable GP(cl)-mediated fusion with NPC1 or its GP(cl) binding domain at any pH tested, while robust fusion was consistently observed with GP from lymphocytic choriomeningitis virus at low pH. Addition of proposed fusion-enhancing factors—cations (Ca(++) and K(+)), a reducing agent, the anionic lipid Bis(Monoacylglycero)Phosphate, and a mixture of cathepsins B and L—did not induce detectable fusion. Our findings are in line with the earlier proposal that an additional factor is required to trigger the full fusion activity of GP(cl) after binding to NPC1. We discuss caveats to our study and what the missing factor(s) might be.",2019 Jul 5,"['Fénéant, Lucie', 'Szymańska-de Wijs, Katarzyna M.', 'Nelson, Elizabeth A.', 'White, Judith M.']",PLoS One,,,True
93a3e9ccff1d9991907c8f959fbfd99f07af5c29,PMC,Interaction between the nasal microbiota and S. pneumoniae in the context of live-attenuated influenza vaccine,http://dx.doi.org/10.1038/s41467-019-10814-9,PMC6611866,31278315,CC BY,"Streptococcus pneumoniae is the main bacterial pathogen involved in pneumonia. Pneumococcal acquisition and colonization density is probably affected by viral co-infections, the local microbiome composition and mucosal immunity. Here, we report the interactions between live-attenuated influenza vaccine (LAIV), successive pneumococcal challenge, and the healthy adult nasal microbiota and mucosal immunity using an experimental human challenge model. Nasal microbiota profiles at baseline are associated with consecutive pneumococcal carriage outcome (non-carrier, low-dense and high-dense pneumococcal carriage), independent of LAIV co-administration. Corynebacterium/Dolosigranulum-dominated profiles are associated with low-density colonization. Lowest rates of natural viral co-infection at baseline and post-LAIV influenza replication are detected in the low-density carriers. Also, we detected the fewest microbiota perturbations and mucosal cytokine responses in the low-density carriers compared to non-carriers or high-density carriers. These results indicate that the complete respiratory ecosystem affects pneumococcal behaviour following challenge, with low-density carriage representing the most stable ecological state.",2019 Jul 5,"['de Steenhuijsen Piters, Wouter A. A.', 'Jochems, Simon P.', 'Mitsi, Elena', 'Rylance, Jamie', 'Pojar, Sherin', 'Nikolaou, Elissavet', 'German, Esther L.', 'Holloway, Mark', 'Carniel, Beatriz F.', 'Chu, Mei Ling J. N.', 'Arp, Kayleigh', 'Sanders, Elisabeth A. M.', 'Ferreira, Daniela M.', 'Bogaert, Debby']",Nat Commun,,,True
6a93af8b84900413c8f93f69f5e6d7c8cad9249a,PMC,Interaction between the nasal microbiota and S. pneumoniae in the context of live-attenuated influenza vaccine,http://dx.doi.org/10.1038/s41467-019-10814-9,PMC6611866,31278315,CC BY,"Streptococcus pneumoniae is the main bacterial pathogen involved in pneumonia. Pneumococcal acquisition and colonization density is probably affected by viral co-infections, the local microbiome composition and mucosal immunity. Here, we report the interactions between live-attenuated influenza vaccine (LAIV), successive pneumococcal challenge, and the healthy adult nasal microbiota and mucosal immunity using an experimental human challenge model. Nasal microbiota profiles at baseline are associated with consecutive pneumococcal carriage outcome (non-carrier, low-dense and high-dense pneumococcal carriage), independent of LAIV co-administration. Corynebacterium/Dolosigranulum-dominated profiles are associated with low-density colonization. Lowest rates of natural viral co-infection at baseline and post-LAIV influenza replication are detected in the low-density carriers. Also, we detected the fewest microbiota perturbations and mucosal cytokine responses in the low-density carriers compared to non-carriers or high-density carriers. These results indicate that the complete respiratory ecosystem affects pneumococcal behaviour following challenge, with low-density carriage representing the most stable ecological state.",2019 Jul 5,"['de Steenhuijsen Piters, Wouter A. A.', 'Jochems, Simon P.', 'Mitsi, Elena', 'Rylance, Jamie', 'Pojar, Sherin', 'Nikolaou, Elissavet', 'German, Esther L.', 'Holloway, Mark', 'Carniel, Beatriz F.', 'Chu, Mei Ling J. N.', 'Arp, Kayleigh', 'Sanders, Elisabeth A. M.', 'Ferreira, Daniela M.', 'Bogaert, Debby']",Nat Commun,,,False
96ec828983678df332879221419bed8196b6b85f,PMC,Interaction between the nasal microbiota and S. pneumoniae in the context of live-attenuated influenza vaccine,http://dx.doi.org/10.1038/s41467-019-10814-9,PMC6611866,31278315,CC BY,"Streptococcus pneumoniae is the main bacterial pathogen involved in pneumonia. Pneumococcal acquisition and colonization density is probably affected by viral co-infections, the local microbiome composition and mucosal immunity. Here, we report the interactions between live-attenuated influenza vaccine (LAIV), successive pneumococcal challenge, and the healthy adult nasal microbiota and mucosal immunity using an experimental human challenge model. Nasal microbiota profiles at baseline are associated with consecutive pneumococcal carriage outcome (non-carrier, low-dense and high-dense pneumococcal carriage), independent of LAIV co-administration. Corynebacterium/Dolosigranulum-dominated profiles are associated with low-density colonization. Lowest rates of natural viral co-infection at baseline and post-LAIV influenza replication are detected in the low-density carriers. Also, we detected the fewest microbiota perturbations and mucosal cytokine responses in the low-density carriers compared to non-carriers or high-density carriers. These results indicate that the complete respiratory ecosystem affects pneumococcal behaviour following challenge, with low-density carriage representing the most stable ecological state.",2019 Jul 5,"['de Steenhuijsen Piters, Wouter A. A.', 'Jochems, Simon P.', 'Mitsi, Elena', 'Rylance, Jamie', 'Pojar, Sherin', 'Nikolaou, Elissavet', 'German, Esther L.', 'Holloway, Mark', 'Carniel, Beatriz F.', 'Chu, Mei Ling J. N.', 'Arp, Kayleigh', 'Sanders, Elisabeth A. M.', 'Ferreira, Daniela M.', 'Bogaert, Debby']",Nat Commun,,,True
a56fc47514bbcbeeab571a5d5cf6ae87dcab2a1e,PMC,QTL-mapping and genomic prediction for bovine respiratory disease in U.S. Holsteins using sequence imputation and feature selection,http://dx.doi.org/10.1186/s12864-019-5941-5,PMC6612181,31277567,CC BY,"BACKGROUND: National genetic evaluations for disease resistance do not exist, precluding the genetic improvement of cattle for these traits. We imputed BovineHD genotypes to whole genome sequence for 2703 Holsteins that were cases or controls for Bovine Respiratory Disease and sampled from either California or New Mexico to construct and compare genomic prediction models. The sequence variation reference dataset comprised variants called for 1578 animals from Run 5 of the 1000 Bull Genomes Project, including 450 Holsteins and 29 animals sequenced from this study population. Genotypes for 9,282,726 variants with minor allele frequencies ≥5% were imputed and used to obtain genomic predictions in GEMMA using a Bayesian Sparse Linear Mixed Model. RESULTS: Variation explained by markers increased from 13.6% using BovineHD data to 14.4% using imputed whole genome sequence data and the resolution of genomic regions detected as harbouring QTL substantially increased. Explained variation in the analysis of the combined California and New Mexico data was less than when data for each state were separately analysed and the estimated genetic correlation between risk of Bovine Respiratory Disease in California and New Mexico Holsteins was − 0.36. Consequently, genomic predictions trained using the data from one state did not accurately predict disease risk in the other state. To determine if a prediction model could be developed with utility in both states, we selected variants within genomic regions harbouring: 1) genes involved in the normal immune response to infection by pathogens responsible for Bovine Respiratory Disease detected by RNA-Seq analysis, and/or 2) QTL identified in the association analysis of the imputed sequence variants. The model based on QTL selected variants is biased but when trained in one state generated BRD risk predictions with positive accuracies in the other state. CONCLUSIONS: We demonstrate the utility of sequence-based and biology-driven model development for genomic selection. Disease phenotypes cannot be routinely recorded in most livestock species and the observed phenotypes may vary in their genomic architecture due to variation in the pathogen composition across environments. Elucidation of trait biology and genetic architecture may guide the development of prediction models with utility across breeds and environments. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-019-5941-5) contains supplementary material, which is available to authorized users.",2019 Jul 5,"['Hoff, Jesse L.', 'Decker, Jared E.', 'Schnabel, Robert D.', 'Seabury, Christopher M.', 'Neibergs, Holly L.', 'Taylor, Jeremy F.']",BMC Genomics,,,True
f2130991992abd3db076407a10aafc3a0c6a64b9,PMC,"2HybridTools, a handy software to facilitate clone identification and mutation mapping from yeast two-hybrid screening",http://dx.doi.org/10.7717/peerj.7245,PMC6612259,31309003,CC BY,"Yeast Two-Hybrid (Y2H) and reverse Two-Hybrid (RY2H) are powerful protein–protein interaction screening methods that rely on the interaction of bait and prey proteins fused to DNA binding (DB) and activation domains (AD), respectively. Y2H allows identification of protein interaction partners using screening libraries, while RY2H is used to determine residues critical to a given protein–protein interaction by exploiting site-directed mutagenesis. Currently, both these techniques still rely on sequencing of positive clones using conventional Sanger sequencing. For Y2H, a screen can yield several positives; the identification of such clones is further complicated by the fact that sequencing products usually contain vector sequence. For RY2H, obtaining a complete sequence is required to identify the full range of residues involved in protein–protein interactions. However, with Sanger sequencing limited to 500–800 nucleotides, sequencing is usually carried from both ends for clones greater than this length. Analysis of such RY2H data thus requires assembly of sequencing products combined with trimming of vector sequences and of low-quality bases at the beginning and ends of sequencing products. Further, RY2H analysis requires collation of mutations that abrogate a DB/AD interaction. Here, we present 2HybridTools, a Java program with a user-friendly interface that allows addressing all these issues inherent to both Y2H and RY2H. Specifically, for Y2H, 2HybridTools enables automated identification of positive clones, while for RY2H, 2HybridTools provides detailed mutation reports as a basis for further investigation of given protein–protein interactions.",2019 Jul 3,"['Cauchy, Pierre', 'Kahn-Perlès, Brigitte', 'Ferrier, Pierre', 'Imbert, Jean', 'Lécine, Patrick']",PeerJ,,,False
ad459f664c704e1ac4f0f8d97d0e194914bb9601,PMC,Essential Oils as Antimicrobial Agents—Myth or Real Alternative?,http://dx.doi.org/10.3390/molecules24112130,PMC6612361,31195752,CC BY,"Herbs and the essential oils derived from them have been used from the beginning of human history for different purposes. Their beneficial properties have been applied to mask unpleasant odors, attract the attention of other people, add flavor and aroma properties to prepared dishes, perfumes, and cosmetics, etc. Herbs and essential oils (EOs) have also been used in medicine because of their biological properties, such as larvicidal action, analgesic and anti-inflammatory properties, antioxidant, fungicide, and antitumor activities, and many more. Many EOs exhibit antimicrobial properties, which is extremely important in fields of science and industry, such as medicine, agriculture, or cosmetology. Among the 250 EOs which are commercially available, about a dozen possess high antimicrobial potential. According to available papers and patents, EOs seem to be a potential alternative to synthetic compounds, especially because of the resistance that has been increasingly developed by pathogenic microorganisms. In this review we summarize the latest research studies about the most-active EOs that are known and used because of their antimicrobial properties. Finally, it is noteworthy that the antimicrobial activities of EOs are not preeminent for all strains. Further investigations should, thus, focus on targeting EOs and microorganisms.",2019 Jun 5,"['Wińska, Katarzyna', 'Mączka, Wanda', 'Łyczko, Jacek', 'Grabarczyk, Małgorzata', 'Czubaszek, Anna', 'Szumny, Antoni']",Molecules,,,True
181c0ab76c45147f22639cff9ae04c8ed12509cf,PMC,Essential Oils as Antimicrobial Agents—Myth or Real Alternative?,http://dx.doi.org/10.3390/molecules24112130,PMC6612361,31195752,CC BY,"Herbs and the essential oils derived from them have been used from the beginning of human history for different purposes. Their beneficial properties have been applied to mask unpleasant odors, attract the attention of other people, add flavor and aroma properties to prepared dishes, perfumes, and cosmetics, etc. Herbs and essential oils (EOs) have also been used in medicine because of their biological properties, such as larvicidal action, analgesic and anti-inflammatory properties, antioxidant, fungicide, and antitumor activities, and many more. Many EOs exhibit antimicrobial properties, which is extremely important in fields of science and industry, such as medicine, agriculture, or cosmetology. Among the 250 EOs which are commercially available, about a dozen possess high antimicrobial potential. According to available papers and patents, EOs seem to be a potential alternative to synthetic compounds, especially because of the resistance that has been increasingly developed by pathogenic microorganisms. In this review we summarize the latest research studies about the most-active EOs that are known and used because of their antimicrobial properties. Finally, it is noteworthy that the antimicrobial activities of EOs are not preeminent for all strains. Further investigations should, thus, focus on targeting EOs and microorganisms.",2019 Jun 5,"['Wińska, Katarzyna', 'Mączka, Wanda', 'Łyczko, Jacek', 'Grabarczyk, Małgorzata', 'Czubaszek, Anna', 'Szumny, Antoni']",Molecules,,,False
308008ca9e72e3b15dfac9be4fea847b58cf975a,PMC,Small Extracellular Vesicles Are Key Regulators of Non-cell Autonomous Intercellular Communication in Senescence via the Interferon Protein IFITM3,http://dx.doi.org/10.1016/j.celrep.2019.05.095,PMC6613042,31242426,CC BY,"Senescence is a cellular phenotype present in health and disease, characterized by a stable cell-cycle arrest and an inflammatory response called senescence-associated secretory phenotype (SASP). The SASP is important in influencing the behavior of neighboring cells and altering the microenvironment; yet, this role has been mainly attributed to soluble factors. Here, we show that both the soluble factors and small extracellular vesicles (sEVs) are capable of transmitting paracrine senescence to nearby cells. Analysis of individual cells internalizing sEVs, using a Cre-reporter system, show a positive correlation between sEV uptake and senescence activation. We find an increase in the number of multivesicular bodies during senescence in vivo. sEV protein characterization by mass spectrometry (MS) followed by a functional siRNA screen identify interferon-induced transmembrane protein 3 (IFITM3) as being partially responsible for transmitting senescence to normal cells. We find that sEVs contribute to paracrine senescence.",2019 Jun 25,"['Borghesan, Michela', 'Fafián-Labora, Juan', 'Eleftheriadou, Olga', 'Carpintero-Fernández, Paula', 'Paez-Ribes, Marta', 'Vizcay-Barrena, Gema', 'Swisa, Avital', 'Kolodkin-Gal, Dror', 'Ximénez-Embún, Pilar', 'Lowe, Robert', 'Martín-Martín, Belen', 'Peinado, Hector', 'Muñoz, Javier', 'Fleck, Roland A.', 'Dor, Yuval', 'Ben-Porath, Ittai', 'Vossenkamper, Anna', 'Muñoz-Espin, Daniel', 'O’Loghlen, Ana']",Cell Rep,,,False
92882bb542056ab5a28160cefa9a8c31db5dd089,PMC,Small Extracellular Vesicles Are Key Regulators of Non-cell Autonomous Intercellular Communication in Senescence via the Interferon Protein IFITM3,http://dx.doi.org/10.1016/j.celrep.2019.05.095,PMC6613042,31242426,CC BY,"Senescence is a cellular phenotype present in health and disease, characterized by a stable cell-cycle arrest and an inflammatory response called senescence-associated secretory phenotype (SASP). The SASP is important in influencing the behavior of neighboring cells and altering the microenvironment; yet, this role has been mainly attributed to soluble factors. Here, we show that both the soluble factors and small extracellular vesicles (sEVs) are capable of transmitting paracrine senescence to nearby cells. Analysis of individual cells internalizing sEVs, using a Cre-reporter system, show a positive correlation between sEV uptake and senescence activation. We find an increase in the number of multivesicular bodies during senescence in vivo. sEV protein characterization by mass spectrometry (MS) followed by a functional siRNA screen identify interferon-induced transmembrane protein 3 (IFITM3) as being partially responsible for transmitting senescence to normal cells. We find that sEVs contribute to paracrine senescence.",2019 Jun 25,"['Borghesan, Michela', 'Fafián-Labora, Juan', 'Eleftheriadou, Olga', 'Carpintero-Fernández, Paula', 'Paez-Ribes, Marta', 'Vizcay-Barrena, Gema', 'Swisa, Avital', 'Kolodkin-Gal, Dror', 'Ximénez-Embún, Pilar', 'Lowe, Robert', 'Martín-Martín, Belen', 'Peinado, Hector', 'Muñoz, Javier', 'Fleck, Roland A.', 'Dor, Yuval', 'Ben-Porath, Ittai', 'Vossenkamper, Anna', 'Muñoz-Espin, Daniel', 'O’Loghlen, Ana']",Cell Rep,,,False
022efb5d64e88419546d697b6a5a96e6bc8a9fab,PMC,Harnessing host–virus evolution in antiviral therapy and immunotherapy,http://dx.doi.org/10.1002/cti2.1067,PMC6613463,31312450,CC BY,"Pathogen resistance and development costs are major challenges in current approaches to antiviral therapy. The high error rate of RNA synthesis and reverse‐transcription confers genome plasticity, enabling the remarkable adaptability of RNA viruses to antiviral intervention. However, this property is coupled to fundamental constraints including limits on the size of information available to manipulate complex hosts into supporting viral replication. Accordingly, RNA viruses employ various means to extract maximum utility from their informationally limited genomes that, correspondingly, may be leveraged for effective host‐oriented therapies. Host‐oriented approaches are becoming increasingly feasible because of increased availability of bioactive compounds and recent advances in immunotherapy and precision medicine, particularly genome editing, targeted delivery methods and RNAi. In turn, one driving force behind these innovations is the increasingly detailed understanding of evolutionarily diverse host–virus interactions, which is the key concern of an emerging field, neo‐virology. This review examines biotechnological solutions to disease and other sustainability issues of our time that leverage the properties of RNA and DNA viruses as developed through co‐evolution with their hosts.",2019 Jul 8,"Heaton, Steven M",Clin Transl Immunology,,,True
2544d85288aa39f592b1e172f8c62040bc1b2ba6,PMC,African Swine Fever Virus Armenia/07 Virulent Strain Controls Interferon Beta Production through the cGAS-STING Pathway,http://dx.doi.org/10.1128/JVI.02298-18,PMC6613762,30918080,CC BY,"African swine fever virus (ASFV) is a complex, cytoplasmic double-stranded DNA (dsDNA) virus that is currently expanding throughout the world. Currently, circulating virulent genotype II Armenia/07-like viruses cause fatal disease in pigs and wild boar, whereas attenuated strains induce infections with various levels of chronic illness. Sensing cytosolic dsDNA, mainly by the key DNA sensor cyclic GMP-AMP synthase (cGAS), leads to the synthesis of type I interferon and involves signaling through STING, TBK1, and IRF3. After phosphorylation, STING translocates from the endoplasmic reticulum to the Golgi compartment and to the perinuclear region, acting as an indispensable adaptor connecting the cytosolic detection of DNA to the TBK1-IRF3 signaling pathway. We demonstrate here that attenuated NH/P68, but not virulent Armenia/07, activates the cGAS-STING-IRF3 cascade very early during infection, inducing STING phosphorylation and trafficking through a mechanism involving cGAMP. Both TBK1 and IRF3 are subsequently activated and, in response to this, a high level of beta interferon (IFN-β) was produced during NH/P68 infection; in contrast, Armenia/07 infection generated IFN-β levels below those of uninfected cells. Our results show that virulent Armenia/07 ASFV controls the cGAS-STING pathway, but these mechanisms are not at play when porcine macrophages are infected with attenuated NH/P68 ASFV. These findings show for the first time the involvement of the cGAS-STING-IRF3 route in ASFV infection, where IFN-β production or inhibition was found after infection by attenuated or virulent ASFV strains, respectively, thus reinforcing the idea that ASFV virulence versus attenuation may be a phenomenon grounded in ASFV-mediated innate immune modulation where the cGAS-STING pathway might play an important role. IMPORTANCE African swine fever, a devastating disease for domestic pigs and wild boar, is currently spreading in Europe, Russia, and China, becoming a global threat with huge economic and ecological consequences. One interesting aspect of ASFV biology is the molecular mechanism leading to high virulence of some strains compared to more attenuated strains, which produce subclinical infections. In this work, we show that the presently circulating virulent Armenia/07 virus blocks the synthesis of IFN-β, a key mediator between the innate and adaptive immune response. Armenia/07 inhibits the cGAS-STING pathway by impairing STING activation during infection. In contrast, the cGAS-STING pathway is efficiently activated during NH/P68 attenuated strain infection, leading to the production of large amounts of IFN-β. Our results show for the first time the relationship between the cGAS-STING pathway and ASFV virulence, contributing to uncover the molecular mechanisms of ASFV virulence and to the rational development of ASFV vaccines.",2019 May 29,"['García-Belmonte, Raquel', 'Pérez-Núñez, Daniel', 'Pittau, Marco', 'Richt, Juergen A.', 'Revilla, Yolanda']",J Virol,,,True
bc0f6f12f18acc7d05e7aea6cae71b6bdae56906,PMC,Natural Killer Cell Receptor Genes in Camels: Another Mammalian Model,http://dx.doi.org/10.3389/fgene.2019.00620,PMC6614441,31312212,CC BY,"Due to production of special homodimeric heavy chain antibodies, somatic hypermutation of their T-cell receptor genes and unusually low diversity of their major histocompatibility complex genes, camels represent an important model for immunogenetic studies. Here, we analyzed genes encoding selected natural killer cell receptors with a special focus on genes encoding receptors for major histocompatibility complex (MHC) class I ligands in the two domestic camel species, Camelus dromedarius and Camelus bactrianus. Based on the dromedary genome assembly CamDro2, we characterized the genetic contents, organization, and variability of two complex genomic regions, the leukocyte receptor complex and the natural killer complex, along with the natural cytotoxicity receptor genes NCR1, NCR2, and NCR3. The genomic organization of the natural killer complex region of camels differs from cattle, the phylogenetically most closely related species. With its minimal set of KLR genes, it resembles this complex in the domestic pig. Similarly, the leukocyte receptor complex of camels is strikingly different from its cattle counterpart. With KIR pseudogenes and few LILR genes, it seems to be simpler than in the pig. The syntenies and protein sequences of the NCR1, NCR2, and NCR3 genes in the dromedary suggest that they could be human orthologues. However, only NCR1 and NCR2 have a structure of functional genes, while NCR3 appears to be a pseudogene. High sequence similarities between the two camel species as well as with the alpaca Vicugna pacos were observed. The polymorphism in all genes analyzed seems to be generally low, similar to the rest of the camel genomes. This first report on natural killer cell receptor genes in camelids adds new data to our understanding of specificities of the camel immune system and its functions, extends our genetic knowledge of the innate immune variation in dromedaries and Bactrian camels, and contributes to studies of natural killer cell receptors evolution in mammals.",2019 Jul 2,"['Futas, Jan', 'Oppelt, Jan', 'Jelinek, April', 'Elbers, Jean P.', 'Wijacki, Jan', 'Knoll, Ales', 'Burger, Pamela A.', 'Horin, Petr']",Front Genet,,,False
5ac39b49492fe7a6f53ad50d840e4ce8ed579e77,PMC,Natural Killer Cell Receptor Genes in Camels: Another Mammalian Model,http://dx.doi.org/10.3389/fgene.2019.00620,PMC6614441,31312212,CC BY,"Due to production of special homodimeric heavy chain antibodies, somatic hypermutation of their T-cell receptor genes and unusually low diversity of their major histocompatibility complex genes, camels represent an important model for immunogenetic studies. Here, we analyzed genes encoding selected natural killer cell receptors with a special focus on genes encoding receptors for major histocompatibility complex (MHC) class I ligands in the two domestic camel species, Camelus dromedarius and Camelus bactrianus. Based on the dromedary genome assembly CamDro2, we characterized the genetic contents, organization, and variability of two complex genomic regions, the leukocyte receptor complex and the natural killer complex, along with the natural cytotoxicity receptor genes NCR1, NCR2, and NCR3. The genomic organization of the natural killer complex region of camels differs from cattle, the phylogenetically most closely related species. With its minimal set of KLR genes, it resembles this complex in the domestic pig. Similarly, the leukocyte receptor complex of camels is strikingly different from its cattle counterpart. With KIR pseudogenes and few LILR genes, it seems to be simpler than in the pig. The syntenies and protein sequences of the NCR1, NCR2, and NCR3 genes in the dromedary suggest that they could be human orthologues. However, only NCR1 and NCR2 have a structure of functional genes, while NCR3 appears to be a pseudogene. High sequence similarities between the two camel species as well as with the alpaca Vicugna pacos were observed. The polymorphism in all genes analyzed seems to be generally low, similar to the rest of the camel genomes. This first report on natural killer cell receptor genes in camelids adds new data to our understanding of specificities of the camel immune system and its functions, extends our genetic knowledge of the innate immune variation in dromedaries and Bactrian camels, and contributes to studies of natural killer cell receptors evolution in mammals.",2019 Jul 2,"['Futas, Jan', 'Oppelt, Jan', 'Jelinek, April', 'Elbers, Jean P.', 'Wijacki, Jan', 'Knoll, Ales', 'Burger, Pamela A.', 'Horin, Petr']",Front Genet,,,True
7e92385d74e531617394983f187f6b4c9ca2f328,PMC,Neuroprotective Effects of Musk of Muskrat on Transient Focal Cerebral Ischemia in Rats,http://dx.doi.org/10.1155/2019/9817949,PMC6614976,31341507,CC BY,"Musk of musk deer has been one of the most precious traditional medicinal materials for treatment of stroke, but trading is prohibited. Musk of muskrat, Ondatra zibethicus, is an accessible substitute for musk of musk deer. However, neuroprotective effects of the musk of muskrat on stroke model are so far unclear. Aim of the study is to determine neuroprotective effects of the musk of muskrat on focal cerebral ischemia. The protective effects against focal cerebral ischemia were evaluated using a model of middle cerebral artery occlusion (90-minute occlusion followed by 24-hour reperfusion). Musk of muskrat was collected from scent bag of muskrat and orally administered at doses of 100 and 300 mg/kg twice at times of 0 and 90 min after occlusion. The effects on sensorimotor dysfunction were investigated by using balance beam test and rotarod test after brain ischemia. The expression of cyclooxygenase-2 (COX-2) was investigated by immunohistochemistry. Oral administration of musk at 300 mg/kg significantly reduced (p<0.001) the infarct volume by 32.4% compared with a vehicle-treated group. Oral administration of musk at 300 mg/kg also ameliorated ischemia-induced spontaneous and vestibule sensorimotor dysfunction in balance beam test and rotarod test compared with control group and COX-2 upregulation. Musk of muskrat may have neuroprotective effects against transient focal cerebral ischemia with recovery of sensorimotor dysfunction. Regarding the immunohistochemistry, the effects of muskrat may be due to anti-inflammatory properties through inhibition of COX-2 expressions.",2019 Jun 25,"['Lee, Donghun', 'Kim, Young-Sik', 'Song, Jungbin', 'Kim, Hocheol']",Evid Based Complement Alternat Med,,,True
9447f072b9c3281b75034071b735888370faab25,PMC,Microarray analysis of infectious bronchitis virus infection of chicken primary dendritic cells,http://dx.doi.org/10.1186/s12864-019-5940-6,PMC6615177,31286855,CC BY,"BACKGROUND: Avian infectious bronchitis virus (IBV) is a major respiratory disease-causing agent in birds that leads to significant losses. Dendritic cells (DCs) are specialised cells responsible for sampling antigens and presenting them to T cells, which also play an essential role in recognising and neutralising viruses. Recent studies have suggested that non-coding RNAs may regulate the functional program of DCs. Expression of host non-coding RNAs changes markedly during infectious bronchitis virus infection, but their role in regulating host immune function has not been explored. Here, microarrays of mRNAs, miRNAs, and lncRNAs were globally performed to analyse how avian DCs respond to IBV. RESULTS: First, we found that IBV stimulation did not enhance the maturation ability of avian DCs. Interestingly, inactivated IBV was better able than IBV to induce DC maturation and activate lymphocytes. We identified 1093 up-regulated and 845 down-regulated mRNAs in IBV-infected avian DCs. Gene Ontology analysis suggested that cellular macromolecule and protein location (GO-BP) and transcription factor binding (GO-MF) were abundant in IBV-stimulated avian DCs. Meanwhile, pathway analysis indicated that the oxidative phosphorylation and leukocyte transendothelial migration signalling pathways might be activated in the IBV group. Moreover, alteration of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) was detected in IBV-stimulated avian DCs. In total, 19 significantly altered (7 up and 12 down) miRNAs and 101 (75 up and 26 down) lncRNAs were identified in the IBV-treated group. Further analysis showed that the actin cytoskeleton and MAPK signal pathway were related to the target genes of IBV-stimulated miRNAs. Finally, our study identified 2 TF-microRNA and 53 TF–microRNA–mRNA interactions involving 1 TF, 2 miRNAs, and 53 mRNAs in IBV-stimulated avian DCs. CONCLUSIONS: Our research suggests a new mechanism to explain why IBV actively blocks innate responses needed for inducing immune gene expression and also provides insight into the pathogenic mechanisms of avian IBV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-019-5940-6) contains supplementary material, which is available to authorized users.",2019 Jul 8,"['Lin, Jian', 'Wang, Zhisheng', 'Wang, Jialu', 'Yang, Qian']",BMC Genomics,,,True
1f345c5a7a02b742ca70ce9233c80a200af974b6,PMC,Pharmaceutical Prescription in Canine Acute Diarrhoea: A Longitudinal Electronic Health Record Analysis of First Opinion Veterinary Practices,http://dx.doi.org/10.3389/fvets.2019.00218,PMC6615257,31334254,CC BY,"Canine acute diarrhoea is frequently observed in first opinion practice, though little is known about commonly used diagnostic or therapeutic management plans, including use of antimicrobials. This retrospective observational study utilised electronic health records augmented with practitioner-completed questionnaires from 3,189 cases (3,159 dogs) collected from 179 volunteer veterinary practices between April 2014 and January 2017. We used multivariable analysis to explore factors potentially associated with pharmaceutical agent prescription, and resolution of clinical signs by 10 days post-initial presentation. Use of bacteriological and/or parasitological diagnostic tests were uncommon (3.2% of cases, 95% confidence interval, CI, 2.4–4.0), though systemic antimicrobials were the most commonly prescribed pharmaceutical agents (49.7% of cases, 95% CI 46.1–53.2). Such prescription was associated with haemorrhagic diarrhoea (odds ratio, OR, 4.1; 95% CI 3.4–5.0), body temperature in excess of 39.0°C, or moderate/severe cases (OR 1.3, 95% CI 1.1–1.7). Gastrointestinal agents (e.g., antacids) were prescribed to 37.7% of cases (95% CI 35.4–39.9), and were most frequently prescribed to vomiting dogs regardless of presence (OR 46.4, 95% CI 19.4–110.8) or absence of blood (OR 17.1, 95% CI 13.4–21.9). Endoparasiticides/endectocides were prescribed to 7.8% of cases (95% CI 6.8–9.0), such prescription being less frequent for moderate/severe cases (OR 0.5, 95% CI 0.4–0.7), though more frequent when weight loss was recorded (OR 3.4, 95% CI 1.3–9.0). Gastrointestinal nutraceuticals (e.g., probiotics) were dispensed to 60.8% of cases (95% CI 57.1–64.6), these cases less frequently presenting with moderate/severe clinical signs (OR 0.6, 95% CI 0.5–0.8). Nearly a quarter of cases were judged lost to follow-up (n=754). Insured (OR 0.7, 95% CI 0.5–0.9); neutered (OR 0.4, 95% CI 0.3–0.5), or vaccinated dogs (OR 0.3, 95% CI 0.3–0.4) were less commonly lost to follow-up. Of remaining dogs, clinical signs were deemed resolved in 95.4% of cases (95% CI 94.6–96.2). Provision of dietary modification advice and gastrointestinal nutraceuticals alone were positively associated with resolution (OR 2.8, 95% CI 1.3–6.1); no such associations were found for pharmaceutical agents, including antimicrobials. Hence, this study supports the view that antimicrobials are largely unnecessary for acute diarrhoea cases; this being of particular importance when considering the global threat posed by antimicrobial resistance.",2019 Jul 2,"['Singleton, David A.', 'Noble, P. J. M.', 'Sánchez-Vizcaíno, Fernando', 'Dawson, Susan', 'Pinchbeck, Gina L.', 'Williams, Nicola J.', 'Radford, Alan D.', 'Jones, Philip H.']",Front Vet Sci,,,True
057a931d8bfabff534eddd75a96af84a1b6b3deb,PMC,A broadly neutralizing germline-like human monoclonal antibody against dengue virus envelope domain III,http://dx.doi.org/10.1371/journal.ppat.1007836,PMC6615639,31242272,CC0,"Dengue is the most widespread vector-borne viral disease caused by dengue virus (DENV) for which there are no safe, effective drugs approved for clinical use. Here, by using sequential antigen panning of a yeast antibody library derived from healthy donors against the DENV envelop protein domain III (DIII) combined with depletion by an entry defective DIII mutant, we identified a cross-reactive human monoclonal antibody (mAb), m366.6, which bound with high affinity to DENV DIII from all four DENV serotypes. Immunogenetic analysis indicated that m366.6 is a germline-like mAb with very few somatic mutations from the closest VH and Vλ germline genes. Importantly, we demonstrated that it potently neutralized DENV both in vitro and in the mouse models of DENV infection without detectable antibody-dependent enhancement (ADE) effect. The epitope of m366.6 was mapped to the highly conserved regions on DIII, which may guide the design of effective dengue vaccine immunogens. Furthermore, as the first germline-like mAb derived from a naïve antibody library that could neutralize all four DENV serotypes, the m366.6 can be a tool for exploring mechanisms of DENV infection, and is a promising therapeutic candidate.",2019 Jun 26,"['Hu, Dan', 'Zhu, Zhongyu', 'Li, Shun', 'Deng, Yongqiang', 'Wu, Yanling', 'Zhang, Nana', 'Puri, Vinita', 'Wang, Chunyu', 'Zou, Peng', 'Lei, Cheng', 'Tian, Xiaolong', 'Wang, Yulu', 'Zhao, Qi', 'Li, Wei', 'Prabakaran, Ponraj', 'Feng, Yang', 'Cardosa, Jane', 'Qin, Chengfeng', 'Zhou, Xiaohui', 'Dimitrov, Dimiter S.', 'Ying, Tianlei']",PLoS Pathog,,,True
61aa22d85170a908912fd1f0c0f86ea251b4e311,PMC,"TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis",http://dx.doi.org/10.1371/journal.pntd.0006983,PMC6615641,31242184,CC BY,"BACKGROUND: T cell immunoglobulin mucin domain-1 (TIM-1) is a phosphatidylserine (PS) receptor, mediating filovirus entry into cells through interactions with PS on virions. TIM-1 expression has been implicated in Ebola virus (EBOV) pathogenesis; however, it remains unclear whether this is due to TIM-1 serving as a filovirus receptor in vivo or, as others have suggested, TIM-1 induces a cytokine storm elicited by T cell/virion interactions. Here, we use a BSL2 model virus that expresses EBOV glycoprotein to demonstrate the importance of TIM-1 as a virus receptor late during in vivo infection. METHODOLOGY/PRINCIPAL FINDINGS: Infectious, GFP-expressing recombinant vesicular stomatitis virus encoding either full length EBOV glycoprotein (EBOV GP/rVSV) or mucin domain deleted EBOV glycoprotein (EBOV GPΔO/rVSV) was used to assess the role of TIM-1 during in vivo infection. GFP-expressing rVSV encoding its native glycoprotein G (G/rVSV) served as a control. TIM-1-sufficient or TIM-1-deficient BALB/c interferon α/β receptor(-/-) mice were challenged with these viruses. While G/rVSV caused profound morbidity and mortality in both mouse strains, TIM-1-deficient mice had significantly better survival than TIM-1-expressing mice following EBOV GP/rVSV or EBOV GPΔO/rVSV challenge. EBOV GP/rVSV or EBOV GPΔO/rVSV in spleen of infected animals was high and unaffected by expression of TIM-1. However, infectious virus in serum, liver, kidney and adrenal gland was reduced late in infection in the TIM-1-deficient mice, suggesting that virus entry via this receptor contributes to virus load. Consistent with higher virus loads, proinflammatory chemokines trended higher in organs from infected TIM-1-sufficient mice compared to the TIM-1-deficient mice, but proinflammatory cytokines were more modestly affected. To assess the role of T cells in EBOV GP/rVSV pathogenesis, T cells were depleted in TIM-1-sufficient and -deficient mice and the mice were challenged with virus. Depletion of T cells did not alter the pathogenic consequences of virus infection. CONCLUSIONS: Our studies provide evidence that at late times during EBOV GP/rVSV infection, TIM-1 increased virus load and associated mortality, consistent with an important role of this receptor in virus entry. This work suggests that inhibitors which block TIM-1/virus interaction may serve as effective antivirals, reducing virus load at late times during EBOV infection.",2019 Jun 26,"['Brunton, Bethany', 'Rogers, Kai', 'Phillips, Elisabeth K.', 'Brouillette, Rachel B.', 'Bouls, Ruayda', 'Butler, Noah S.', 'Maury, Wendy']",PLoS Negl Trop Dis,,,True
aa6d90b5eb890db486db2e09d3b28db343a7d48c,PMC,Preventive Behavioral Responses to the 2015 Middle East Respiratory Syndrome Coronavirus Outbreak in Korea,http://dx.doi.org/10.3390/ijerph16122161,PMC6616393,31216779,CC BY,"This study examined the public’s preventive behavioral responses during the 2015 Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in Korea and the influencing factors. Two cross-sectional telephone surveys were conducted by Gallup Korea using random digit dialing in June 2015 (n = 2004). The main outcome variables were nonpharmaceutical preventive measures (survey (1): Measures for reducing transmission (handwashing, face masks); and survey (2): Measures for avoiding contact with others). Multiple logistic regression was used to identify the factors influencing preventive behaviors. In survey (1), 60.3% of respondents reported more frequent handwashing and 15.5% reported wearing face masks at least once due to the MERS-CoV epidemic. In survey (2), 41–56% of respondents reported practicing avoidance measures. The concerned group was more likely to practice reducing transmission measures (odds ratio (OR) 4.5; 95% confidence interval (CI) 3.3–6.1) and avoidance measures (OR = 9.6; 95% CI, 6.4–14.4). The respondents who had low trust in president or ruling party had a higher practice rate of reducing transmission measures (OR = 1.7; 95% CI, 1.2–2.6) and avoidance measures (OR = 2.1; 95% CI, 1.2–3.5). Cooperative prevention measures need appropriated public concern based on effective risk communication.",2019 Jun 18,"['Jang, Won Mo', 'Cho, Sanghyun', 'Jang, Deok Hyun', 'Kim, Un-Na', 'Jung, Hyemin', 'Lee, Jin Yong', 'Eun, Sang Jun']",Int J Environ Res Public Health,,,True
39cf0b0febc53a4655489e3e458a93585b68093d,PMC,Changes in Serum Amyloid A (SAA) Concentration in Arabian Endurance Horses During First Training Season,http://dx.doi.org/10.3390/ani9060330,PMC6616404,31181740,CC BY,"Sport training leads to adaptation to physical effort that is reflected by the changes in blood parameters. In equine endurance athletes, blood testing is accepted as a support in training, however, only the changes before versus after exercise in creatine phosphokinase activity (CPK) and basic blood parameters are usually measured. This study is the first longitudinal investigation of the changes in routinely measured blood parameters and, additionally, serum amyloid A (SAA), during seven months, in Arabian horses introduced to endurance training and competing in events for young horses. It has been determined that CPK, aspartate aminotransferase (AST), packed cell volume (PCV), hemoglobin concentration, red blood cell count (RBC), and concentration of total serum protein (TSP) slightly increased after training sessions and competitions in similar manner. The increase in white blood cell (WBC) count was higher after competitions and SAA increased only after competitions. Total protein concentration was the only parameter that increased with training during a 7-month program. SAA indicated only in the case of heavy effort, and, it thus may be helpful in the monitoring of training in young horses. In an optimal program, its concentration should not increase after a training session but only after heavy effort, which should not be repeated too often.",2019 Jun 8,"['Witkowska-Piłaszewicz, Olga', 'Bąska, Piotr', 'Czopowicz, Michał', 'Żmigrodzka, Magdalena', 'Szczepaniak, Jarosław', 'Szarska, Ewa', 'Winnicka, Anna', 'Cywińska, Anna']",Animals (Basel),,,True
84dfb0723d3a0b1243850099eef4def974f44a8d,PMC,Mapping the drivers of within-host pathogen evolution using massive data sets,http://dx.doi.org/10.1038/s41467-019-10724-w,PMC6616926,31289267,CC BY,"Differences among hosts, resulting from genetic variation in the immune system or heterogeneity in drug treatment, can impact within-host pathogen evolution. Genetic association studies can potentially identify such interactions. However, extensive and correlated genetic population structure in hosts and pathogens presents a substantial risk of confounding analyses. Moreover, the multiple testing burden of interaction scanning can potentially limit power. We present a Bayesian approach for detecting host influences on pathogen evolution that exploits vast existing data sets of pathogen diversity to improve power and control for stratification. The approach models key processes, including recombination and selection, and identifies regions of the pathogen genome affected by host factors. Our simulations and empirical analysis of drug-induced selection on the HIV-1 genome show that the method recovers known associations and has superior precision-recall characteristics compared to other approaches. We build a high-resolution map of HLA-induced selection in the HIV-1 genome, identifying novel epitope-allele combinations.",2019 Jul 9,"['Palmer, Duncan S.', 'Turner, Isaac', 'Fidler, Sarah', 'Frater, John', 'Goedhals, Dominique', 'Goulder, Philip', 'Huang, Kuan-Hsiang Gary', 'Oxenius, Annette', 'Phillips, Rodney', 'Shapiro, Roger', 'Vuuren, Cloete van', 'McLean, Angela R.', 'McVean, Gil']",Nat Commun,,,True
5ecad9a5929549f90a9aa621ea0548c62d1385ca,PMC,Mapping the drivers of within-host pathogen evolution using massive data sets,http://dx.doi.org/10.1038/s41467-019-10724-w,PMC6616926,31289267,CC BY,"Differences among hosts, resulting from genetic variation in the immune system or heterogeneity in drug treatment, can impact within-host pathogen evolution. Genetic association studies can potentially identify such interactions. However, extensive and correlated genetic population structure in hosts and pathogens presents a substantial risk of confounding analyses. Moreover, the multiple testing burden of interaction scanning can potentially limit power. We present a Bayesian approach for detecting host influences on pathogen evolution that exploits vast existing data sets of pathogen diversity to improve power and control for stratification. The approach models key processes, including recombination and selection, and identifies regions of the pathogen genome affected by host factors. Our simulations and empirical analysis of drug-induced selection on the HIV-1 genome show that the method recovers known associations and has superior precision-recall characteristics compared to other approaches. We build a high-resolution map of HLA-induced selection in the HIV-1 genome, identifying novel epitope-allele combinations.",2019 Jul 9,"['Palmer, Duncan S.', 'Turner, Isaac', 'Fidler, Sarah', 'Frater, John', 'Goedhals, Dominique', 'Goulder, Philip', 'Huang, Kuan-Hsiang Gary', 'Oxenius, Annette', 'Phillips, Rodney', 'Shapiro, Roger', 'Vuuren, Cloete van', 'McLean, Angela R.', 'McVean, Gil']",Nat Commun,,,True
16f1872aff5293a40e4e8047a141b18b3a35a28e,PMC,Mapping the drivers of within-host pathogen evolution using massive data sets,http://dx.doi.org/10.1038/s41467-019-10724-w,PMC6616926,31289267,CC BY,"Differences among hosts, resulting from genetic variation in the immune system or heterogeneity in drug treatment, can impact within-host pathogen evolution. Genetic association studies can potentially identify such interactions. However, extensive and correlated genetic population structure in hosts and pathogens presents a substantial risk of confounding analyses. Moreover, the multiple testing burden of interaction scanning can potentially limit power. We present a Bayesian approach for detecting host influences on pathogen evolution that exploits vast existing data sets of pathogen diversity to improve power and control for stratification. The approach models key processes, including recombination and selection, and identifies regions of the pathogen genome affected by host factors. Our simulations and empirical analysis of drug-induced selection on the HIV-1 genome show that the method recovers known associations and has superior precision-recall characteristics compared to other approaches. We build a high-resolution map of HLA-induced selection in the HIV-1 genome, identifying novel epitope-allele combinations.",2019 Jul 9,"['Palmer, Duncan S.', 'Turner, Isaac', 'Fidler, Sarah', 'Frater, John', 'Goedhals, Dominique', 'Goulder, Philip', 'Huang, Kuan-Hsiang Gary', 'Oxenius, Annette', 'Phillips, Rodney', 'Shapiro, Roger', 'Vuuren, Cloete van', 'McLean, Angela R.', 'McVean, Gil']",Nat Commun,,,False
35d2665a9d06c67cd85ff2ed458c9df80902d4bd,PMC,Mapping the drivers of within-host pathogen evolution using massive data sets,http://dx.doi.org/10.1038/s41467-019-10724-w,PMC6616926,31289267,CC BY,"Differences among hosts, resulting from genetic variation in the immune system or heterogeneity in drug treatment, can impact within-host pathogen evolution. Genetic association studies can potentially identify such interactions. However, extensive and correlated genetic population structure in hosts and pathogens presents a substantial risk of confounding analyses. Moreover, the multiple testing burden of interaction scanning can potentially limit power. We present a Bayesian approach for detecting host influences on pathogen evolution that exploits vast existing data sets of pathogen diversity to improve power and control for stratification. The approach models key processes, including recombination and selection, and identifies regions of the pathogen genome affected by host factors. Our simulations and empirical analysis of drug-induced selection on the HIV-1 genome show that the method recovers known associations and has superior precision-recall characteristics compared to other approaches. We build a high-resolution map of HLA-induced selection in the HIV-1 genome, identifying novel epitope-allele combinations.",2019 Jul 9,"['Palmer, Duncan S.', 'Turner, Isaac', 'Fidler, Sarah', 'Frater, John', 'Goedhals, Dominique', 'Goulder, Philip', 'Huang, Kuan-Hsiang Gary', 'Oxenius, Annette', 'Phillips, Rodney', 'Shapiro, Roger', 'Vuuren, Cloete van', 'McLean, Angela R.', 'McVean, Gil']",Nat Commun,,,True
a232d55159ae4e3d7eb30a4e9bb04494dd438344,PMC,Efficacy of Houttuynia eye drops for the treatment of vernal keratoconjunctivitis: A systemic review and meta-analysis protocol,http://dx.doi.org/10.1097/MD.0000000000016196,PMC6617420,31261561,CC BY,"BACKGROUND: Vernal keratoconjunctivitis (VKC) is a common eye disease and can result in permanent decrease or loss of vision. Houttuynia eye drops (HED) is used for the treatment of VKC. However, the clinical evidence of HED has not been well concluded. Herein, we described a proposed systemic review and meta-analysis to evaluate the clinical efficacy of HED for the treatment of VKC. METHODS: Six electronic databases (Medline, Embase, the Cochrane database, Chinese National Knowledge Infrastructure, Wanfang database, and Chinese Biology and Medicine database) will be searched for randomized controlled trials (RCTs) which evaluating the clinical efficacy of HED for the treatment of VKC. Studies meet the eligibility criteria will be included. Data of the included studies will be extracted and the quality will also be evaluated. Data synthesis will be performed using RevMan software. Sensitivity analysis and publication bias will also be investigated. RESULTS: This study will provide high-quality systemic review and synthesis of RCTs on efficacy of HED for the treatment of VKC. CONCLUSION: This systemic review and meta-analysis will conclude the efficacy of HED for the treatment of VKC. REGISTRATION: PROSPERO CRD42019124737",2019 Jun 28,"['Yu, Lingyan', 'Chen, Xueying', 'Yu, Zhenwei']",Medicine (Baltimore),,,True
c6b5bfea0defb38a81a9c9dd23b4d0f272ac05da,PMC,Virucidal activity of Garcinia parvifolia leaf extracts in animal cell culture,http://dx.doi.org/10.1186/s12906-019-2586-5,PMC6617885,31291936,CC BY,"BACKGROUND: Garcinia species contain bioactive compounds such as flavonoids, xanthones, triterpernoids, and benzophenones with antibacterial, antifungal, anti-inflammatory, and antioxidant activities. In addition, many of these compounds show interesting biological properties such as anti-human immunodeficiency virus activity. Garcinia parvifolia is used in traditional medicine. Currently, the antiviral activity of G. parvifolia is not known. METHODS: This study was conducted to determine the effects of ethyl acetate (45 L Ea), ethanol (45 L Et), and hexane (45 L H) leaf extracts of G. parvifolia on the infectivity of pseudorabies virus (PrV) in Vero cells. The antiviral effects of the extracts were determined by cytopathic effect (CPE), inhibition, attachment, and virucidal assays. RESULTS: The 50% cytotoxicity concentration (CC(50)) values obtained were 237.5, 555.0, and < 1.25 μg/mL for 45 L Ea, 45 L Et, and 45 L H, respectively. The 45 L Ea showed the greatest viral inhibition potency of 75% at 125 μg/mL. Both 45 L Ea and 45 l Et caused 100% residual viral inhibition at 250 μg/mL. The selectivity index values for 45 L Ea, 45 L Et, and 45 L H were 2.65, 1.75, and 0.10 showing that 45 L Ea had the greatest antiviral activity among the three extracts. CONCLUSION: This study showed that ethyl acetate is the best solvent to be used to obtain extract from G. parvifolia leaves with potent antiviral activities.",2019 Jul 10,"['Adnan, Aziera', 'Allaudin, Zeenathul Nazariah', 'Hani, Homayoun', 'Loh, Hwei-San', 'Khoo, Teng-Jin', 'Ting, Kang Nee', 'Abdullah, Rasedee']",BMC Complement Altern Med,,,True
eea9d5e3d2244b3ecfb5e909515e00a4a3cabaa7,PMC,The impact of rapid molecular diagnostic testing for respiratory viruses on outcomes for emergency department patients,http://dx.doi.org/10.5694/mja2.50049,PMC6617970,30838671,CC BY,"OBJECTIVE: To determine whether rapid polymerase chain reaction (PCR) testing for influenza and respiratory syncytial viruses (RSV) in emergency departments (EDs) is associated with better patient and laboratory outcomes than standard multiplex PCR testing. DESIGN, SETTING: A before‐and‐after study in four metropolitan EDs in New South Wales. PARTICIPANTS: 1491 consecutive patients tested by standard multiplex PCR during July–December 2016, and 2250 tested by rapid PCR during July–December 2017. MAIN OUTCOME MEASURES: Hospital admissions; ED length of stay (LOS); test turnaround time; patient receiving test result before leaving the ED; ordering of other laboratory tests. RESULTS: Compared with those tested by standard PCR, fewer patients tested by rapid PCR were admitted to hospital (73.3% v 77.7%; P < 0.001) and more received their test results before leaving the ED (67.4% v 1.3%; P < 0.001); the median test turnaround time was also shorter (2.4 h [IQR, 1.6–3.9 h] v 26.7 h [IQR, 21.2–37.8 h]). The proportion of patients admitted to hospital was also lower in the rapid PCR group for both children under 18 (50.6% v 66.6%; P < 0.001) and patients over 60 years of age (84.3% v 91.8%; P < 0.001). Significantly fewer blood culture, blood gas, sputum culture, and respiratory bacterial and viral serology tests were ordered for patients tested by rapid PCR. ED LOS was similar for the rapid (7.4 h; IQR, 5.0–12.9 h) and standard PCR groups (6.5 h; IQR, 4.2–11.9 h; P = 0.27). CONCLUSION: Rapid PCR testing of ED patients for influenza virus and RSV was associated with better outcomes on a range of indicators, suggesting benefits for patients and the health care system. A formal cost–benefit analysis should be undertaken.",2019 Apr 5,"['Wabe, Nasir', 'Li, Ling', 'Lindeman, Robert', 'Yimsung, Ruth', 'Dahm, Maria R', 'Clezy, Kate', 'McLennan, Susan', 'Westbrook, Johanna', 'Georgiou, Andrew']",Med J Aust,,,True
29fc968d79a48ca92712892284a7a18b62de7e07,PMC,The impact of rapid molecular diagnostic testing for respiratory viruses on outcomes for emergency department patients,http://dx.doi.org/10.5694/mja2.50049,PMC6617970,30838671,CC BY,"OBJECTIVE: To determine whether rapid polymerase chain reaction (PCR) testing for influenza and respiratory syncytial viruses (RSV) in emergency departments (EDs) is associated with better patient and laboratory outcomes than standard multiplex PCR testing. DESIGN, SETTING: A before‐and‐after study in four metropolitan EDs in New South Wales. PARTICIPANTS: 1491 consecutive patients tested by standard multiplex PCR during July–December 2016, and 2250 tested by rapid PCR during July–December 2017. MAIN OUTCOME MEASURES: Hospital admissions; ED length of stay (LOS); test turnaround time; patient receiving test result before leaving the ED; ordering of other laboratory tests. RESULTS: Compared with those tested by standard PCR, fewer patients tested by rapid PCR were admitted to hospital (73.3% v 77.7%; P < 0.001) and more received their test results before leaving the ED (67.4% v 1.3%; P < 0.001); the median test turnaround time was also shorter (2.4 h [IQR, 1.6–3.9 h] v 26.7 h [IQR, 21.2–37.8 h]). The proportion of patients admitted to hospital was also lower in the rapid PCR group for both children under 18 (50.6% v 66.6%; P < 0.001) and patients over 60 years of age (84.3% v 91.8%; P < 0.001). Significantly fewer blood culture, blood gas, sputum culture, and respiratory bacterial and viral serology tests were ordered for patients tested by rapid PCR. ED LOS was similar for the rapid (7.4 h; IQR, 5.0–12.9 h) and standard PCR groups (6.5 h; IQR, 4.2–11.9 h; P = 0.27). CONCLUSION: Rapid PCR testing of ED patients for influenza virus and RSV was associated with better outcomes on a range of indicators, suggesting benefits for patients and the health care system. A formal cost–benefit analysis should be undertaken.",2019 Apr 5,"['Wabe, Nasir', 'Li, Ling', 'Lindeman, Robert', 'Yimsung, Ruth', 'Dahm, Maria R', 'Clezy, Kate', 'McLennan, Susan', 'Westbrook, Johanna', 'Georgiou, Andrew']",Med J Aust,,,False
4cc3f3b34e4353ec33df7c231e22112232ae7218,PMC,Hijacking the Supplies: Metabolism as a Novel Facet of Virus-Host Interaction,http://dx.doi.org/10.3389/fimmu.2019.01533,PMC6617997,31333664,CC BY,"Viral replication is a process that involves an extremely high turnover of cellular molecules. Since viruses depend on the host cell to obtain the macromolecules needed for their proper replication, they have evolved numerous strategies to shape cellular metabolism and the biosynthesis machinery of the host according to their specific needs. Technologies for the rigorous analysis of metabolic alterations in cells have recently become widely available and have greatly expanded our knowledge of these crucial host–pathogen interactions. We have learned that most viruses enhance specific anabolic pathways and are highly dependent on these alterations. Since uninfected cells are far more plastic in their metabolism, targeting of the virus-induced metabolic alterations is a promising strategy for specific antiviral therapy and has gained great interest recently. In this review, we summarize the current advances in our understanding of metabolic adaptations during viral infections, with a particular focus on the utilization of this information for therapeutic application.",2019 Jul 3,"['Mayer, Katharina A.', 'Stöckl, Johannes', 'Zlabinger, Gerhard J.', 'Gualdoni, Guido A.']",Front Immunol,,,True
18efb24780930c0ee4343fd31b37b39ce3c3b315,PMC,Application of Aptamers in Virus Detection and Antiviral Therapy,http://dx.doi.org/10.3389/fmicb.2019.01462,PMC6618307,31333603,CC BY,"Viral infections can cause serious diseases for humans and animals. Accurate and early detection of viruses is often crucial for clinical diagnosis and therapy. Aptamers are mostly single-stranded nucleotide sequences that are artificially synthesized by an in vitro technology known as the Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Similar to antibodies, aptamers bind specifically to their targets. However, compared with antibody, aptamers are easy to synthesize and modify and can bind to a broad range of targets. Thus, aptamers are promising for detecting viruses and treating viral infections. In this review, we briefly introduce aptamer-based biosensors (aptasensors) and describe their applications in rapid detection of viruses and as antiviral agents in treating infections. We summarize available data about the use of aptamers to detect and inhibit viruses. Furthermore, for the first time, we list aptamers specific to different viruses that have been screened out but have not yet been used for detecting viruses or treating viral infections. Finally, we analyze barriers and developing perspectives in the application of aptamer-based virus detection and therapeutics.",2019 Jul 3,"['Zou, Xinran', 'Wu, Jing', 'Gu, Jiaqi', 'Shen, Li', 'Mao, Lingxiang']",Front Microbiol,,,True
aa8c9ce5d6162a02fc51e0d95b27e63a709ca140,PMC,Alveolar Macrophage Dysfunction and Increased PD-1 Expression During Chronic SIV Infection of Rhesus Macaques,http://dx.doi.org/10.3389/fimmu.2019.01537,PMC6618664,31333668,CC BY,"HIV infected individuals have been shown to be pre-disposed to pulmonary infections even while receiving anti-retroviral therapy. Alveolar macrophages (AMs) play a critical role in lung innate immunity, but contradictory results have been reported regarding their functionality following HIV infection. Here, using the SIV rhesus macaque model, we document the effect of SIV infection on the phenotypic and functional properties of AMs. Following infection with SIV(mac251), AMs in bronchoalveolar lavage (BAL) sampled over 2- to 20-weeks post-infection (wpi) were compared to those in BAL samples from naïve macaques. AM expression of proinflammatory cytokines TNF-α, IL-6, IL-1β, and chemokine RANTES drastically increased 2-wpi compared to AMs of naïve macaques (p < 0.0001 for all), but dropped significantly with progression to chronic infection. Phagocytic activity of AMs 2-and 4-wpi was elevated compared to AMs of naive animals (p = 0.0005, p = 0.0004, respectively) but significantly decreased by 12-wpi (p = 0.0022, p = 0.0019, respectively). By 20-wpi the ability of AMs from chronically infected animals to perform SIV-specific antibody-dependent phagocytosis (ADP) was also diminished (p = 0.028). Acute SIV infection was associated with increased FcγRIII expression which subsequently declined with disease progression. Frequency of FcγRIII(+) AMs showed a strong trend toward correlation with SIV-specific ADP, and at 2-wpi FcγRIII expression negatively correlated with viral load (r = −0.6819; p = 0.0013), suggesting a contribution to viremia control. Importantly, PD-1 was found to be expressed on AMs and showed a strong trend toward correlation with plasma viral load (r = 0.8266; p = 0.058), indicating that similar to over-expression on T-cells, PD-1 expression on AMs may also be associated with disease progression. Further, AMs predominantly expressed PD-L2, which remained consistent over the course of infection. PD-1 blockade enhanced SIV-specific ADP by AMs from chronic infection indicating that the PD-1/PD-L2 pathway may modulate functional activity of AMs at that stage. These findings provide new insight into the dynamics of SIV infection leading to AM dysfunction and alteration of pulmonary innate immunity. Our results suggest new pathways to exploit in developing therapies targeting pulmonary disease susceptibility in HIV-infected individuals.",2019 Jul 3,"['Hunegnaw, Ruth', 'Mushtaq, Zuena', 'Enyindah-Asonye, Gospel', 'Hoang, Tanya', 'Robert-Guroff, Marjorie']",Front Immunol,,,True
6cef5ad67e84f17e96de7c2d9af64487a4637cb9,PMC,A fully automated sample-to-answer PCR system for easy and sensitive detection of dengue virus in human serum and mosquitos,http://dx.doi.org/10.1371/journal.pone.0218139,PMC6619671,31291289,CC BY,"BACKGROUND: The insulated isothermal PCR (iiPCR) technology enables consistent PCR amplification and detection in a simple heating device. A pan-dengue virus (DENV) RT-iiPCR, targeting the 5’ untranslated region, was validated previously on the semi-automated POCKIT combo system (involving separate devices for nucleic acid extraction and PCR amplification/detection) to offer performance comparable to a laboratory real-time PCR. Working on the same technologies, a compact automated sample-in-answer-out system (POCKIT Central Nucleic Acid Analyser) has been available commercially for iiPCR, minimizing human error risks and allowing easy molecular bio-detection near points of need. Here, we evaluated the analytical and clinical performance of the pan-DENV RT-iiPCR on the fully automated system by comparison to those on the semi-automated system. METHODOLOGY/PRINCIPAL FINDINGS: Testing sera containing serial diluted DENV-1, -2, -3, or -4 cell culture stock, the pan-DENV RT-iiPCR system had similar 100% detection endpoints on the two systems; i.e. at 1, 10, 1 and 10 PFU/ml, respectively, on the fully automated system, and at 10, 1, 10 and 10 PFU/ml, respectively, on the semi-automated system. Furthermore, both fully automated and semi-automated PCR system can detect all four DENV serotypes in mosquitos. Clinical performance of the reagent on the two systems was evaluated by testing 60 human serum samples. Both systems detected the same 40 samples (ten DENV-1, -2, -3, and -4 positive each) and did not detect the other 20; 100% agreement (κ = 1) was found between the two systems. CONCLUSIONS/SIGNIFICANCE: With performance comparable to a previously validated system, the fully-automated PCR system allows applications of the pan-DENV reagent as a useful tool near points of need to facilitate easy, fast and effective detection of dengue virus and help mitigate versatile public health challenges in the control and management of dengue disease.",2019 Jul 10,"['Tsai, Jih-Jin', 'Liu, Wei-Liang', 'Lin, Ping-Chang', 'Huang, Bo-Yi', 'Tsai, Ching-Yi', 'Lee, Pei-Yu Alison', 'Tsai, Yun-Long', 'Chou, Pin-Hsing', 'Chung, Simon', 'Liu, Li-Teh', 'Chen, Chun-Hong']",PLoS One,,,True
ef20a0cd67ce018cf061f154bd8be9d0e58d0f23,PMC,"Effectiveness of zinc supplementation on diarrhea and average daily gain in pre-weaned dairy calves: A double-blind, block-randomized, placebo-controlled clinical trial",http://dx.doi.org/10.1371/journal.pone.0219321,PMC6619766,31291305,CC BY,"The objective of this clinical trial was to evaluate the effectiveness of zinc supplementation on diarrhea and average daily weight gain (ADG) in pre-weaned dairy calves. A total of 1,482 healthy Holstein heifer and bull calves from a large California dairy were enrolled at 24 to 48 hours of age until hutch exit at approximately 90 days of age. Calves were block-randomized by time to one of three treatments: 1) placebo, 2) zinc methionine (ZM), or 3) zinc sulfate (ZS) administered in milk once daily for 14 days. Serum total protein at enrollment and body weight at birth, treatment end, and hutch exit were measured. Fecal consistency was assessed daily for 28 days post-enrollment. For a random sample of 127 calves, serum zinc concentrations before and after treatment and a fecal antigen ELISA at diarrhea start and resolution for Escherichia coli K99, rotavirus, coronavirus, and Cryptosporidium parvum were performed. Linear regression showed that ZM-treated bull calves had 22 g increased ADG compared to placebo-treated bulls (P = 0.042). ZM-treated heifers had 9 g decreased ADG compared to placebo-treated heifers (P = 0.037), after adjusting for average birth weight. Sex-stratified models showed that high birth weight heifers treated with ZM gained more than placebo-treated heifers of the same birth weight, which suggests a dose-response effect rather than a true sex-specific effect of ZM on ADG. Cox regression showed that ZM and ZS-treated calves had a 14.7% (P = 0.015) and 13.9% (P = 0.022) reduced hazard of diarrhea, respectively, compared to placebo-treated calves. Calves supplemented for at least the first five days of diarrhea with ZM and ZS had a 21.4% (P = 0.027) and 13.0% (P = 0.040) increased hazard of cure from diarrhea, respectively, compared to placebo-treated calves. Logistic regression showed that the odds of microbiological cure at diarrhea resolution for rotavirus, C. parvum, or any single fecal pathogen was not different between treatment groups. Zinc supplementation delayed diarrhea and expedited diarrhea recovery in pre-weaned calves. Additionally, zinc improved weight gain differentially in bulls compared to heifers, indicating a research need for sex-specific dosing.",2019 Jul 10,"['Feldmann, Hillary R.', 'Williams, Deniece R.', 'Champagne, John D.', 'Lehenbauer, Terry W.', 'Aly, Sharif S.']",PLoS One,,,True
a9a03b8e5d632fb01f973df42763da7fb0179629,PMC,Analysis of Synonymous Codon Usage Bias in Flaviviridae Virus,http://dx.doi.org/10.1155/2019/5857285,PMC6620835,31346520,CC BY,"BACKGROUND: Flaviviridae viruses are single-stranded, positive-sense RNA viruses, which threat human constantly mediated by mosquitoes, ticks, and sandflies. Considering the recent increase in the prevalence of the family virus and its risk potential, we investigated the codon usage pattern to understand its evolutionary processes and provide some useful data to develop the medications for most of Flaviviridae viruses. RESULTS: The overall extent of codon usage bias in 65 Flaviviridae viruses is low with the average value of GC contents being 50.5% and the highest value being 55.9%; the lowest value is 40.2%. ENC values of Flaviviridae virus genes vary from 48.75 to 57.83 with a mean value of 55.56. U- and A-ended codons are preferred in the Flaviviridae virus. Correlation analysis shows that the positive correlation between ENC value and GC content at the third nucleotide positions was significant in this family virus. The result of analysis of ENC, neutrality plot analysis, and correlation analysis revealed that codon usage bias of all the viruses was affected mainly by natural selection. Meanwhile, according to correspondence analysis (CoA) based on RSCU and phylogenetic analysis, the Flaviviridae viruses mainly are made up of two groups, Group I (Yellow fever virus, Apoi virus, Tembusu virus, Dengue virus 1, and others) and Group II (West Nile virus lineage 2, Japanese encephalitis virus, Usutu virus, Kedougou virus, and others). CONCLUSIONS: All in, the bias of codon usage pattern is affected not only by compositional constraints but also by natural selection. Phylogenetic analysis also illustrates that codon usage bias of virus can serve as an effective means of evolutionary classification in Flaviviridae virus.",2019 Jun 27,"['Yao, Huipeng', 'Chen, Mengyu', 'Tang, Zizhong']",Biomed Res Int,,,True
576b829eeb6838282aa2ffdfa925301e2888bb9f,PMC,"The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function",http://dx.doi.org/10.1371/journal.pntd.0007537,PMC6623546,31251739,CC BY,"Infection by Zika virus (ZIKV) is linked to microcephaly and other neurological disorders, posing a significant health threat. Innate immunity is the first line of defense against invading pathogens, but relatively little is understood regarding host intrinsic mechanisms that guard against ZIKV. Here, we show that host tripartite motif-containing protein 56 (TRIM56) poses a barrier to ZIKV infection in cells of neural, epithelial and fibroblast origins. Overexpression of TRIM56, but not an E3 ligase-dead mutant or one lacking a short C-terminal portion, inhibited ZIKV RNA replication. Conversely, depletion of TRIM56 increased viral RNA levels. Although the C-terminal region of TRIM56 bears sequence homology to NHL repeat of TRIM-NHL proteins that regulate miRNA activity, knockout of Dicer, which abolishes production of miRNAs, had no demonstrable effect on ZIKV restriction imposed by TRIM56. Rather, we found that TRIM56 is an RNA-binding protein that associates with ZIKV RNA in infected cells. Moreover, a recombinant TRIM56 fragment comprising the C-terminal 392 residues captured ZIKV RNA in cell-free reactions, indicative of direct interaction. Remarkably, deletion of a short C-terminal tail portion abrogated the TRIM56-ZIKV RNA interaction, concomitant with a loss in antiviral activity. Altogether, our study reveals TRIM56 is an RNA binding protein that acts as a ZIKV restriction factor and provides new insights into the antiviral mechanism by which this E3 ligase tackles flavivirus infections.",2019 Jun 28,"['Yang, Darong', 'Li, Nan L.', 'Wei, Dahai', 'Liu, Baoming', 'Guo, Fang', 'Elbahesh, Husni', 'Zhang, Yunzhi', 'Zhou, Zhi', 'Chen, Guo-Yun', 'Li, Kui']",PLoS Negl Trop Dis,,,True
37a57b9c5e9aff55b1657cea3de690c9435cd7c4,PMC,Genomic analysis of respiratory syncytial virus infections in households and utility in inferring who infects the infant,http://dx.doi.org/10.1038/s41598-019-46509-w,PMC6624209,31296922,CC BY,"Infants (under 1-year-old) are at most risk of life threatening respiratory syncytial virus (RSV) disease. RSV epidemiological data alone has been insufficient in defining who acquires infection from whom (WAIFW) within households. We investigated RSV genomic variation within and between infected individuals and assessed its potential utility in tracking transmission in households. Over an entire single RSV season in coastal Kenya, nasal swabs were collected from members of 20 households every 3–4 days regardless of symptom status and screened for RSV nucleic acid. Next generation sequencing was used to generate >90% RSV full-length genomes for 51.1% of positive samples (191/374). Single nucleotide polymorphisms (SNPs) observed during household infection outbreaks ranged from 0–21 (median: 3) while SNPs observed during single-host infection episodes ranged from 0–17 (median: 1). Using the viral genomic data alone there was insufficient resolution to fully reconstruct within-household transmission chains. For households with clear index cases, the most likely source of infant infection was via a toddler (aged 1 to <3 years-old) or school-aged (aged 6 to <12 years-old) co-occupant. However, for best resolution of WAIFW within households, we suggest an integrated analysis of RSV genomic and epidemiological data.",2019 Jul 11,"['Agoti, Charles N.', 'Phan, My V. T.', 'Munywoki, Patrick K.', 'Githinji, George', 'Medley, Graham F.', 'Cane, Patricia A.', 'Kellam, Paul', 'Cotten, Matthew', 'Nokes, D. James']",Sci Rep,,,False
266c1240291949d87000170237a0de20daacec67,PMC,Genomic analysis of respiratory syncytial virus infections in households and utility in inferring who infects the infant,http://dx.doi.org/10.1038/s41598-019-46509-w,PMC6624209,31296922,CC BY,"Infants (under 1-year-old) are at most risk of life threatening respiratory syncytial virus (RSV) disease. RSV epidemiological data alone has been insufficient in defining who acquires infection from whom (WAIFW) within households. We investigated RSV genomic variation within and between infected individuals and assessed its potential utility in tracking transmission in households. Over an entire single RSV season in coastal Kenya, nasal swabs were collected from members of 20 households every 3–4 days regardless of symptom status and screened for RSV nucleic acid. Next generation sequencing was used to generate >90% RSV full-length genomes for 51.1% of positive samples (191/374). Single nucleotide polymorphisms (SNPs) observed during household infection outbreaks ranged from 0–21 (median: 3) while SNPs observed during single-host infection episodes ranged from 0–17 (median: 1). Using the viral genomic data alone there was insufficient resolution to fully reconstruct within-household transmission chains. For households with clear index cases, the most likely source of infant infection was via a toddler (aged 1 to <3 years-old) or school-aged (aged 6 to <12 years-old) co-occupant. However, for best resolution of WAIFW within households, we suggest an integrated analysis of RSV genomic and epidemiological data.",2019 Jul 11,"['Agoti, Charles N.', 'Phan, My V. T.', 'Munywoki, Patrick K.', 'Githinji, George', 'Medley, Graham F.', 'Cane, Patricia A.', 'Kellam, Paul', 'Cotten, Matthew', 'Nokes, D. James']",Sci Rep,,,True
a09e4bffa272479f66c164f2e137cb44760ec827,PMC,Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein,http://dx.doi.org/10.1038/s41467-019-10897-4,PMC6624210,31296843,CC BY,"Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). The epitopes and mechanisms of mAbs targeting non-RBD regions have not been well characterized yet. Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. Structure determination and mutagenesis experiments reveal the epitope and critical residues on the NTD for 7D10 binding and neutralization. Further experiments indicate that the neutralization by 7D10 is not solely dependent on the inhibition of DPP4 binding, but also acts after viral cell attachment, inhibiting the pre-fusion to post-fusion conformational change of the spike. These properties give 7D10 a wide neutralization breadth and help explain its synergistic effects with several RBD-targeting antibodies.",2019 Jul 11,"['Zhou, Haixia', 'Chen, Yingzhu', 'Zhang, Shuyuan', 'Niu, Peihua', 'Qin, Kun', 'Jia, Wenxu', 'Huang, Baoying', 'Zhang, Senyan', 'Lan, Jun', 'Zhang, Linqi', 'Tan, Wenjie', 'Wang, Xinquan']",Nat Commun,,,False
641250a7e9d096165233d7b850218598a8e66715,PMC,Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein,http://dx.doi.org/10.1038/s41467-019-10897-4,PMC6624210,31296843,CC BY,"Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). The epitopes and mechanisms of mAbs targeting non-RBD regions have not been well characterized yet. Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. Structure determination and mutagenesis experiments reveal the epitope and critical residues on the NTD for 7D10 binding and neutralization. Further experiments indicate that the neutralization by 7D10 is not solely dependent on the inhibition of DPP4 binding, but also acts after viral cell attachment, inhibiting the pre-fusion to post-fusion conformational change of the spike. These properties give 7D10 a wide neutralization breadth and help explain its synergistic effects with several RBD-targeting antibodies.",2019 Jul 11,"['Zhou, Haixia', 'Chen, Yingzhu', 'Zhang, Shuyuan', 'Niu, Peihua', 'Qin, Kun', 'Jia, Wenxu', 'Huang, Baoying', 'Zhang, Senyan', 'Lan, Jun', 'Zhang, Linqi', 'Tan, Wenjie', 'Wang, Xinquan']",Nat Commun,,,False
3f72e0ed409b7f7529202dfdf496a4060800a732,PMC,Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein,http://dx.doi.org/10.1038/s41467-019-10897-4,PMC6624210,31296843,CC BY,"Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). The epitopes and mechanisms of mAbs targeting non-RBD regions have not been well characterized yet. Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. Structure determination and mutagenesis experiments reveal the epitope and critical residues on the NTD for 7D10 binding and neutralization. Further experiments indicate that the neutralization by 7D10 is not solely dependent on the inhibition of DPP4 binding, but also acts after viral cell attachment, inhibiting the pre-fusion to post-fusion conformational change of the spike. These properties give 7D10 a wide neutralization breadth and help explain its synergistic effects with several RBD-targeting antibodies.",2019 Jul 11,"['Zhou, Haixia', 'Chen, Yingzhu', 'Zhang, Shuyuan', 'Niu, Peihua', 'Qin, Kun', 'Jia, Wenxu', 'Huang, Baoying', 'Zhang, Senyan', 'Lan, Jun', 'Zhang, Linqi', 'Tan, Wenjie', 'Wang, Xinquan']",Nat Commun,,,False
1fb860b35fac03bc319a2d12de832b65ca392c55,PMC,Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein,http://dx.doi.org/10.1038/s41467-019-10897-4,PMC6624210,31296843,CC BY,"Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). The epitopes and mechanisms of mAbs targeting non-RBD regions have not been well characterized yet. Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. Structure determination and mutagenesis experiments reveal the epitope and critical residues on the NTD for 7D10 binding and neutralization. Further experiments indicate that the neutralization by 7D10 is not solely dependent on the inhibition of DPP4 binding, but also acts after viral cell attachment, inhibiting the pre-fusion to post-fusion conformational change of the spike. These properties give 7D10 a wide neutralization breadth and help explain its synergistic effects with several RBD-targeting antibodies.",2019 Jul 11,"['Zhou, Haixia', 'Chen, Yingzhu', 'Zhang, Shuyuan', 'Niu, Peihua', 'Qin, Kun', 'Jia, Wenxu', 'Huang, Baoying', 'Zhang, Senyan', 'Lan, Jun', 'Zhang, Linqi', 'Tan, Wenjie', 'Wang, Xinquan']",Nat Commun,,,True
e584b536fcbb3da70855c7f8d81c15319b0e9b7b,PMC,"Spread and clinical severity of respiratory syncytial virus A genotype ON1 in Germany, 2011–2017",http://dx.doi.org/10.1186/s12879-019-4266-y,PMC6624929,31299924,CC BY,"BACKGROUND: The Respiratory Syncytial Virus (RSV) A genotype ON1, which was first detected in Ontario (Canada) in 2010/11, appeared in Germany in 2011/12. Preliminary observations suggested a higher clinical severity in children infected with this new genotype. We investigated spread and disease severity of RSV-A ON1 in pediatric in- and outpatient settings. METHODS: During 2010/11 to 2016/17, clinical characteristics and respiratory samples from children with acute respiratory tract infections (RTI) were obtained from ongoing surveillance studies in 33 pediatric practices (PP), one pediatric hospital ward (PW) and 23 pediatric intensive care units (PICU) in Germany. RSV was detected in the respiratory samples by PCR; genotypes were identified by sequencing. Within each setting, clinical severity markers were compared between RSV-A ON1 and RSV-A non-ON1 genotypes. RESULTS: A total of 603 children with RSV-RTI were included (132 children in PP, 288 in PW, and 183 in PICU). Of these children, 341 (56.6%) were infected with RSV-A, 235 (39.0%) with RSV-B, and one child (0.2%) with both RSV-A and RSV-B; in 26 (4.3%) children, the subtype could not be identified. In the 341 RSV-A positive samples, genotype ON1 was detected in 247 (72.4%), NA1 in 92 (26.9%), and GA5 in 2 children (0.6%). RSV-A ON1, rarely observed in 2011/12, was the predominant RSV-A genotype in all settings by 2012/13 and remained predominant until 2016/17. Children in PP or PW infected with RSV-A ON1 did not show a more severe clinical course of disease compared with RSV-A non-ON1 infections. In the PICU group, hospital stay was one day longer (median 8 days, inter-quartile range (IQR) 7–12 vs. 7 days, IQR 5–9; p = 0.02) and duration of oxygen treatment two days longer (median 6 days, IQR 4–9 vs. 4 days, IQR 2–6; p = 0.03) for children infected with RSV-A ON1. CONCLUSIONS: In children, RSV-A ON1 largely replaced RSV-A non-ON1 genotypes within two seasons and remained the predominant RSV-A genotype in Germany during subsequent seasons. A higher clinical severity of RSV-A ON1 was observed within the group of children receiving PICU treatment, whereas in other settings clinical severity of RSV-A ON1 and non-ON1 genotypes was largely similar. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-4266-y) contains supplementary material, which is available to authorized users.",2019 Jul 12,"['Streng, Andrea', 'Goettler, David', 'Haerlein, Miriam', 'Lehmann, Lisa', 'Ulrich, Kristina', 'Prifert, Christiane', 'Krempl, Christine', 'Weißbrich, Benedikt', 'Liese, Johannes G.']",BMC Infect Dis,,,True
437ea4d132e4263cc2841e01fb19da51c566d0a1,PMC,Simple framework for real-time forecast in a data-limited situation: the Zika virus (ZIKV) outbreaks in Brazil from 2015 to 2016 as an example,http://dx.doi.org/10.1186/s13071-019-3602-9,PMC6624944,31300061,CC BY,"BACKGROUND: In 2015–2016, Zika virus (ZIKV) caused serious epidemics in Brazil. The key epidemiological parameters and spatial heterogeneity of ZIKV epidemics in different states in Brazil remain unclear. Early prediction of the final epidemic (or outbreak) size for ZIKV outbreaks is crucial for public health decision-making and mitigation planning. We investigated the spatial heterogeneity in the epidemiological features of ZIKV across eight different Brazilian states by using simple non-linear growth models. RESULTS: We fitted three different models to the weekly reported ZIKV cases in eight different states and obtained an R(2) larger than 0.995. The estimated average values of basic reproduction numbers from different states varied from 2.07 to 3.41, with a mean of 2.77. The estimated turning points of the epidemics also varied across different states. The estimation of turning points nevertheless is stable and real-time. The forecast of the final epidemic size (attack rate) is reasonably accurate, shortly after the turning point. The knowledge of the epidemic turning point is crucial for accurate real-time projection of the outbreak. CONCLUSIONS: Our simple models fitted the epidemic reasonably well and thus revealed the spatial heterogeneity in the epidemiological features across Brazilian states. The knowledge of the epidemic turning point is crucial for real-time projection of the outbreak size. Our real-time estimation framework is able to yield a reliable prediction of the final epidemic size. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-019-3602-9) contains supplementary material, which is available to authorized users.",2019 Jul 12,"['Zhao, Shi', 'Musa, Salihu S.', 'Fu, Hao', 'He, Daihai', 'Qin, Jing']",Parasit Vectors,,,True
52e898e9b4110cbc6a8beac32cd86672f96489ca,PMC,The threat of climate change to non-dengue-endemic countries: increasing risk of dengue transmission potential using climate and non-climate datasets,http://dx.doi.org/10.1186/s12889-019-7282-3,PMC6625070,31296193,CC BY,"BACKGROUND: Dengue is a major public health problem in the tropics and sub-tropics, but the disease is less known to non-dengue-endemic countries including in Northeast Asia. However, an unexpected dengue outbreak occurred in 2014 in Japan. Given that autochthonous (domestic) dengue cases had not been reported for the past 70 years in Japan, this outbreak was highly unusual and suggests that several environmental factors might have changed in a way that favors vector mosquitoes in the Northeast Asian region. METHODS: A Climate Risk Factor (CRF) index, as validated in previous work, was constructed using climate and non-climate factors. This CRF index was compared to the number of reported dengue cases in Tokyo, Japan where the outbreak was observed in 2014. In order to identify high-risk areas, the CRF index was further estimated at the 5 km by 5 km resolution and mapped for Japan and South Korea. RESULTS: The high-risk areas determined by the CRF index corresponded well to the provinces where a high number of autochthonous cases were reported during the outbreak in Japan. At the provincial-level, high-risk areas for dengue fever were the Eastern part of Tokyo and Kanakawa, the South-Eastern part of Saitama, and the North-Western part of Chiba. While a relatively small number of high-risk areas were identified in South Korea compared with Japan, the high-risk areas in South Korea include popular tourist destinations where international visitors have been increasing. CONCLUSION: The recent dengue outbreak in Japan may signal that the two adjacent non-dengue-endemic countries are also exposed to the risk of temporal and sporadic behavior of dengue fever. It is critical to understand potential high-risk areas for future outbreaks and to set up appropriate prevention activities at the governmental-level.",2019 Jul 11,"['Lee, Jung-Seok', 'Farlow, Andrew']",BMC Public Health,,,True
06249faa885cabbce6eccdf1e40ffe2f43fb5092,PMC,"Using routine testing data to understand circulation patterns of influenza A, respiratory syncytial virus and other respiratory viruses in Victoria, Australia",http://dx.doi.org/10.1017/S0950268819001055,PMC6625191,31364539,CC BY,"Several studies have reported evidence of interference between respiratory viruses: respiratory viruses rarely reach their epidemic peak concurrently and there appears to be a negative association between infection with one respiratory virus and co-infection with another. We used results spanning 16 years (2002–2017) of a routine diagnostic multiplex panel that tests for nine respiratory viruses to further investigate these interactions in Victoria, Australia. Time series analyses were used to plot the proportion positive for each virus. The seasonality of all viruses included was compared with respiratory syncytial virus (RSV) and influenza A virus using cross-correlations. Logistic regression was used to explore the likelihood of co-infection with one virus given infection with another. Seasonal peaks were observed each year for influenza A and RSV and less frequently for influenza B, coronavirus and parainfluenza virus. RSV circulated an average of 6 weeks before influenza A. Co-infection with another respiratory virus was less common with picornavirus, RSV or influenza A infection. Our findings provide further evidence of a temporal relationship in the circulation of respiratory viruses. A greater understanding of the interaction between respiratory viruses may enable better prediction of the timing and magnitude of respiratory virus epidemics.",2019 Jun 17,"['Price, O. H.', 'Sullivan, S. G.', 'Sutterby, C.', 'Druce, J.', 'Carville, K. S.']",Epidemiol Infect,,,True
f35e7fd874f981f6af45b5c75df121c99dc968b4,PMC,Preparation and characterization of a single-domain antibody specific for the porcine epidemic diarrhea virus spike protein,http://dx.doi.org/10.1186/s13568-019-0834-1,PMC6626092,31300902,CC BY,"Porcine epidemic diarrhea (PED) is a diarrheal disease of swine caused by porcine epidemic diarrhea virus (PEDV). It is characterized by acute watery diarrhea, dehydration and vomiting in swine of all ages and is especially fatal for neonatal and postweaning piglets. The spike protein of PEDV plays an important role in mediating virus attachment and fusion to target cells, and recent studies also reported that the neutralizing epitopes of the spike protein were mainly located in the S1 subunit, which makes it a candidate for vaccine development and clinical diagnosis. In this study, we successfully constructed an immune phage display single-domain antibody library with a library size of 3.4 × 10(6). A single-domain antibody, named S7, specific for the spike protein of PEDV was identified from the phage display single-domain antibody library. S7 could be expressed in a soluble form in E. coli, bound to the spike protein of PEDV in ELISA and stained the PEDV virus in Vero cells, but it showed no neutralization activity on PEDV. These results indicated the potent application of the S7 antibody as an imaging probe or as a candidate for the development of a diagnostic assay. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13568-019-0834-1) contains supplementary material, which is available to authorized users.",2019 Jul 12,"['Bao, Fuxiang', 'Wang, Lixin', 'Zhao, Xinxin', 'Lu, Ting', 'Na, A. Mi', 'Wang, Xuefei', 'Cao, Jinshan', 'Du, Yanan']",AMB Express,,,False
fec3f745a9b28ad09219b8a5a83433af27cc5b01,PMC,Preparation and characterization of a single-domain antibody specific for the porcine epidemic diarrhea virus spike protein,http://dx.doi.org/10.1186/s13568-019-0834-1,PMC6626092,31300902,CC BY,"Porcine epidemic diarrhea (PED) is a diarrheal disease of swine caused by porcine epidemic diarrhea virus (PEDV). It is characterized by acute watery diarrhea, dehydration and vomiting in swine of all ages and is especially fatal for neonatal and postweaning piglets. The spike protein of PEDV plays an important role in mediating virus attachment and fusion to target cells, and recent studies also reported that the neutralizing epitopes of the spike protein were mainly located in the S1 subunit, which makes it a candidate for vaccine development and clinical diagnosis. In this study, we successfully constructed an immune phage display single-domain antibody library with a library size of 3.4 × 10(6). A single-domain antibody, named S7, specific for the spike protein of PEDV was identified from the phage display single-domain antibody library. S7 could be expressed in a soluble form in E. coli, bound to the spike protein of PEDV in ELISA and stained the PEDV virus in Vero cells, but it showed no neutralization activity on PEDV. These results indicated the potent application of the S7 antibody as an imaging probe or as a candidate for the development of a diagnostic assay. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13568-019-0834-1) contains supplementary material, which is available to authorized users.",2019 Jul 12,"['Bao, Fuxiang', 'Wang, Lixin', 'Zhao, Xinxin', 'Lu, Ting', 'Na, A. Mi', 'Wang, Xuefei', 'Cao, Jinshan', 'Du, Yanan']",AMB Express,,,True
c0bd429ecee8c353025af075ab372a8a40874cec,PMC,Rhinovirus replication and innate immunity in highly differentiated human airway epithelial cells,http://dx.doi.org/10.1186/s12931-019-1120-0,PMC6626354,31299975,CC BY,"BACKGROUND: Human rhinovirus (HRV) infections are the primary cause of the common cold and are a major trigger for exacerbations of lower airway diseases, such as asthma and chronic obstructive pulmonary diseases. Although human bronchial epithelial cells (HBE) are the natural host for HRV infections, much of our understanding of how HRV replicates and induces host antiviral responses is based on studies using non-airway cell lines (e.g. HeLa cells). The current study examines the replication cycle of HRV, and host cell responses, in highly differentiated cultures of HBE. METHODS: Highly differentiated cultures of HBE were exposed to initial infectious doses ranging from 10(4) to 10(1) 50% tissue culture-infective dose (TCID(50)) of purified HRV-16, and responses were monitored up to 144 h after infection. Viral genomic RNA and negative strand RNA template levels were monitored, along with levels of type I and II interferons and selected antivirals. RESULTS: Regardless of initial infectious dose, relatively constant levels of both genomic and negative strand RNA are generated during replication, with negative strand copy numbers being10,000-fold lower than those of genomic strands. Infections were limited to a small percentage of ciliated cells and did not result in any overt signs of epithelial death. Importantly, regardless of infectious dose, HRV-16 infections were cleared by HBE in the absence of immune cells. Levels of type I and type III interferons (IFNs) varied with initial infectious dose, implying that factors other than levels of double-stranded RNA regulate IFN induction, but the time-course of HRV-16 clearance HBE was the same regardless of levels of IFNs produced. Patterns of antiviral viperin and ISG15 expression suggest they may be generated in an IFN-independent manner during HRV-16 infections. CONCLUSIONS: These data challenge a number of aspects of dogma generated from studies in HeLa cells and emphasize the importance of appropriate cell context when studying HRV infections.",2019 Jul 12,"['Warner, Stephanie M.', 'Wiehler, Shahina', 'Michi, Aubrey N.', 'Proud, David']",Respir Res,,,True
c8f9c5d7e30e601b4ea6e3c42696177c57aa1c47,PMC,Viral Appropriation: Laying Claim to Host Nuclear Transport Machinery,http://dx.doi.org/10.3390/cells8060559,PMC6627039,31181773,CC BY,"Protein nuclear transport is an integral process to many cellular pathways and often plays a critical role during viral infection. To overcome the barrier presented by the nuclear membrane and gain access to the nucleus, virally encoded proteins have evolved ways to appropriate components of the nuclear transport machinery. By binding karyopherins, or the nuclear pore complex, viral proteins influence their own transport as well as the transport of key cellular regulatory proteins. This review covers how viral proteins can interact with different components of the nuclear import machinery and how this influences viral replicative cycles. We also highlight the effects that viral perturbation of nuclear transport has on the infected host and how we can exploit viruses as tools to study novel mechanisms of protein nuclear import. Finally, we discuss the possibility that drugs targeting these transport pathways could be repurposed for treating viral infections.",2019 Jun 8,"['Tessier, Tanner M.', 'Dodge, Mackenzie J.', 'Prusinkiewicz, Martin A.', 'Mymryk, Joe S.']",Cells,,,True
798a5016be0c05f728460661deff95d394346513,PMC,Slow-Binding Inhibition of Tyrosinase by Ecklonia cava Phlorotannins,http://dx.doi.org/10.3390/md17060359,PMC6627058,31208149,CC BY,"Tyrosinase inhibitors improve skin whitening by inhibiting the formation of melanin precursors in the skin. The inhibitory activity of seven phlorotannins (1–7), triphlorethol A (1), eckol (2), 2-phloroeckol (3), phlorofucofuroeckol A (4), 2-O-(2,4,6-trihydroxyphenyl)-6,6′-bieckol (5), 6,8′-bieckol (6), and 8,8′-bieckol (7), from Ecklonia cava was tested against tyrosinase, which converts tyrosine into dihydroxyphenylalanine. Compounds 3 and 5 had IC(50) values of 7.0 ± 0.2 and 8.8 ± 0.1 μM, respectively, in competitive mode, with K(i) values of 8.2 ± 1.1 and 5.8 ± 0.8 μM. Both compounds showed the characteristics of slow-binding inhibitors over the time course of the enzyme reaction. Compound 3 had a single-step binding mechanism and compound 5 a two-step-binding mechanism. With stable AutoDock scores of −6.59 and −6.68 kcal/mol, respectively, compounds 3 and 5 both interacted with His85 and Asn260 at the active site.",2019 Jun 16,"['Kim, Jang Hoon', 'Lee, Sunggun', 'Park, Saerom', 'Park, Ji Soo', 'Kim, Young Ho', 'Yang, Seo Young']",Mar Drugs,,,True
0d7c95184b8a77a7fc0e35995ddc804ba4145429,PMC,The Basics and the Advancements in Diagnosis of Bacterial Lower Respiratory Tract Infections,http://dx.doi.org/10.3390/diagnostics9020037,PMC6627325,30987144,CC BY,"Lower respiratory tract infections (LRTIs) are the leading infectious cause of death and the sixth-leading cause of death overall worldwide. Streptococcus pneumoniae, with more than 90 serotypes, remains the most common identified cause of community-acquired acute bacterial pneumonia. Antibiotics treat LRTIs with a bacterial etiology. With the potential for antibiotic-resistant bacteria, defining the etiology of the LRTI is imperative for appropriate patient treatment. C-reactive protein and procalcitonin are point-of-care tests that may differentiate bacterial versus viral etiologies of LRTIs. Major advancements are currently advancing the ability to make rapid diagnoses and identification of the bacterial etiology of LRTIs, which will continue to support antimicrobial stewardship, and is the focus of this review.",2019 Apr 3,"['Noviello, Stephanie', 'Huang, David B.']",Diagnostics (Basel),,,True
99f61ec3a18d65b10e7df69531368c3afae01e45,PMC,Characterizing Eckol as a Therapeutic Aid: A Systematic Review,http://dx.doi.org/10.3390/md17060361,PMC6627842,31216636,CC BY,"The marine biosphere is a treasure trove of natural bioactive secondary metabolites and the richest source of structurally diverse and unique compounds, such as phlorotannins and halo-compounds, with high therapeutic potential. Eckol is a precursor compound representing the dibenzo-1,4-dioxin class of phlorotannins abundant in the Ecklonia species, which are marine brown algae having a ubiquitous distribution. In search of compounds having biological activity from macro algae during the past three decades, this particular compound has attracted massive attention for its multiple therapeutic properties and health benefits. Although several varieties of marine algae, seaweed, and phlorotannins have already been well scrutinized, eckol deserves a place of its own because of the therapeutic properties it possesses. The relevant information about this particular compound has not yet been collected in one place; therefore, this review focuses on its biological applications, including its potential health benefits and possible applications to restrain diseases leading to good health. The facts compiled in this review could contribute to novel insights into the functions of eckol and potentially enable its use in different uninvestigated fields.",2019 Jun 18,"['Manandhar, Bandana', 'Paudel, Pradeep', 'Seong, Su Hui', 'Jung, Hyun Ah', 'Choi, Jae Sue']",Mar Drugs,,,True
303c666ccc5e060cf609a6d6acbe0ef7b5e508cd,PMC,Special Issue: MicroRNA Regulation in Health and Disease,http://dx.doi.org/10.3390/genes10060457,PMC6628077,31208024,CC BY,,2019 Jun 15,"['Subramanian, Subbaya', 'Steer, Clifford J.']",Genes (Basel),,,True
0b6962f3ef4cb5e76d6ccd144af840b6aec67474,PMC,Activation of the autophagy pathway by Torovirus infection is irrelevant for virus replication,http://dx.doi.org/10.1371/journal.pone.0219428,PMC6629058,31306441,CC BY,"Autophagy is a conserved eukaryotic process that mediates lysosomal degradation of cytoplasmic macromolecules and damaged organelles, also exerting an important role in the elimination of intracellular pathogens. Despite the antiviral role of autophagy, many studies suggest that some positive-stranded RNA viruses exploit this pathway to facilitate their own replication. In this study, we demonstrate that the equine torovirus Berne virus (BEV), the prototype member of the Torovirus genus (Coronaviridae Family, Nidovirales Order), induces autophagy at late times post-infection. Conversion of microtubule associated protein 1B light chain 3 (LC3) from cytosolic (LC3 I) to the membrane associated form (LC3 II), a canonical marker of autophagosome formation, is enhanced in BEV infected cells. However, neither autophagy induction, via starvation, nor pharmacological blockade significantly affect BEV replication. Similarly, BEV infection is not altered in autophagy deficient cells lacking either Beclin 1 or LC3B protein expression. Unexpectedly, the cargo receptor p62, a selective autophagy receptor, aggregates within the region where the BEV main protease (M(pro)) localizes. This finding, coupled with observation that BEV replication also induces ER stress at the time when selective autophagy is taking place, suggests that the autophagy pathway is activated in response to the hefty accumulation of virus-encoded polypeptides during the late phase of BEV infection.",2019 Jul 15,"['Ávila-Pérez, Ginés', 'Diaz-Beneitez, Elisabet', 'Cubas-Gaona, Liliana L.', 'Nieves-Molina, Gliselle', 'Rodríguez, Juan Ramón', 'Rodríguez, José F.', 'Rodríguez, Dolores']",PLoS One,,,True
5080b4cb5df826f641dc6602e27dcca510ccada8,PMC,Selective and competitive inhibition of kynurenine aminotransferase 2 by glycyrrhizic acid and its analogues,http://dx.doi.org/10.1038/s41598-019-46666-y,PMC6629613,31308447,CC BY,"The enzyme kynurenine aminotransferase (KAT) catalyses the conversion of kynurenine (KYN) to kynurenic acid (KYNA). Although the isozymes KAT1–4 have been identified, KYNA is mainly produced by KAT2 in brain tissues. KNYA is an antagonist of N-methyl-D-aspartate and α-7-nicotinic acetylcholine receptors, and accumulation of KYNA in the brain has been associated with the pathology of schizophrenia. Therefore, KAT2 could be exploited as a therapeutic target for the management of schizophrenia. Although currently available KAT2 inhibitors irreversibly bind to pyridoxal 5′-phosphate (PLP), inhibition via this mechanism may cause adverse side effects because of the presence of other PLP-dependent enzymes. Therefore, we identified novel selective KAT2 inhibitors by screening approximately 13,000 molecules. Among these, glycyrrhizic acid (GL) and its analogues, glycyrrhetinic acid (GA) and carbenoxolone (CBX), were identified as KAT2 inhibitors. These compounds were highly selective for KAT2 and competed with its substrate KYN, but had no effects on the other 3 KAT isozymes. Furthermore, we demonstrated that in complex structures that were predicted in docking calculations, GL, GA and CBX were located on the same surface as the aromatic ring of KYN. These results indicate that GL and its analogues are highly selective and competitive inhibitors of KAT2.",2019 Jul 15,"['Yoshida, Yukihiro', 'Fujigaki, Hidetsugu', 'Kato, Koichi', 'Yamazaki, Kyoka', 'Fujigaki, Suwako', 'Kunisawa, Kazuo', 'Yamamoto, Yasuko', 'Mouri, Akihiro', 'Oda, Akifumi', 'Nabeshima, Toshitaka', 'Saito, Kuniaki']",Sci Rep,,,True
f401da36e7206731f86a12c49781c3d1b36347f9,PMC,Reverse Engineering Provides Insights on the Evolution of Subgroups A to E Avian Sarcoma and Leukosis Virus Receptor Specificity †,http://dx.doi.org/10.3390/v11060497,PMC6630264,31151254,CC BY,"The initial step of retrovirus entry—the interaction between the virus envelope glycoprotein trimer and a cellular receptor—is complex, involving multiple, noncontiguous determinants in both proteins that specify receptor choice, binding affinity and the ability to trigger conformational changes in the viral glycoproteins. Despite the complexity of this interaction, retroviruses have the ability to evolve the structure of their envelope glycoproteins to use a different cellular protein as receptors. The highly homologous subgroup A to E Avian Sarcoma and Leukosis Virus (ASLV) glycoproteins belong to the group of class 1 viral fusion proteins with a two-step triggering mechanism that allows experimental access to intermediate structures during the fusion process. We and others have taken advantage of replication-competent ASLVs and exploited genetic selection strategies to force the ASLVs to naturally evolve and acquire envelope glycoprotein mutations to escape the pressure on virus entry and still yield a functional replicating virus. This approach allows for the simultaneous selection of multiple mutations in multiple functional domains of the envelope glycoprotein that may be required to yield a functional virus. Here, we review the ASLV family and experimental system and the reverse engineering approaches used to understand the evolution of ASLV receptor usage.",2019 May 30,"Federspiel, Mark J.",Viruses,,,True
2269f102137c683d0a7871a9ea5110298bd3598c,PMC,Investigation of Fugitive Aerosols Released into the Environment during High-Flow Therapy,http://dx.doi.org/10.3390/pharmaceutics11060254,PMC6630289,31159408,CC BY,"Background: Nebulised medical aerosols are designed to deliver drugs to the lungs to aid in the treatment of respiratory diseases. However, an unintended consequence is the potential for fugitive emissions during patient treatment, which may pose a risk factor in both clinical and homecare settings. Methods: The current study examined the potential for fugitive emissions, using albuterol sulphate as a tracer aerosol during high-flow therapy. A nasal cannula was connected to a head model or alternatively, a interface was connected to a tracheostomy tube in combination with a simulated adult and paediatric breathing profile. Two aerodynamic particle sizers (APS) recorded time-series aerosol concentrations and size distributions at two different distances relative to the simulated patient. Results: The results showed that the quantity and characteristics of the fugitive emissions were influenced by the interface type, patient type and supplemental gas-flow rate. There was a trend in the adult scenarios; as the flow rate increased, the fugitive emissions and the mass median aerodynamic diameter (MMAD) of the aerosol both decreased. The fugitive emissions were comparable when using the adult breathing profiles for the nasal cannula and tracheostomy interfaces; however, there was a noticeable distinction between the two interfaces when compared for the paediatric breathing profiles. The highest recorded aerosol concentration was 0.370 ± 0.046 mg m(−3) from the tracheostomy interface during simulated paediatric breathing with a gas-flow rate of 20 L/min. The averaged MMAD across all combinations ranged from 1.248 to 1.793 µm by the APS at a distance of 0.8 m away from the patient interface. Conclusions: Overall, the results highlight the potential for secondary inhalation of fugitive emissions released during simulated aerosol treatment with concurrent high-flow therapy. The findings will help in developing policy and best practice for risk mitigation from fugitive emissions.",2019 Jun 1,"['McGrath, James A.', 'O’Toole, Ciarraí', 'Bennett, Gavin', 'Joyce, Mary', 'Byrne, Miriam A.', 'MacLoughlin, Ronan']",Pharmaceutics,,,True
bf4079c3d98edc1f61c82d706a38dffe455332f2,PMC,Investigation of Fugitive Aerosols Released into the Environment during High-Flow Therapy,http://dx.doi.org/10.3390/pharmaceutics11060254,PMC6630289,31159408,CC BY,"Background: Nebulised medical aerosols are designed to deliver drugs to the lungs to aid in the treatment of respiratory diseases. However, an unintended consequence is the potential for fugitive emissions during patient treatment, which may pose a risk factor in both clinical and homecare settings. Methods: The current study examined the potential for fugitive emissions, using albuterol sulphate as a tracer aerosol during high-flow therapy. A nasal cannula was connected to a head model or alternatively, a interface was connected to a tracheostomy tube in combination with a simulated adult and paediatric breathing profile. Two aerodynamic particle sizers (APS) recorded time-series aerosol concentrations and size distributions at two different distances relative to the simulated patient. Results: The results showed that the quantity and characteristics of the fugitive emissions were influenced by the interface type, patient type and supplemental gas-flow rate. There was a trend in the adult scenarios; as the flow rate increased, the fugitive emissions and the mass median aerodynamic diameter (MMAD) of the aerosol both decreased. The fugitive emissions were comparable when using the adult breathing profiles for the nasal cannula and tracheostomy interfaces; however, there was a noticeable distinction between the two interfaces when compared for the paediatric breathing profiles. The highest recorded aerosol concentration was 0.370 ± 0.046 mg m(−3) from the tracheostomy interface during simulated paediatric breathing with a gas-flow rate of 20 L/min. The averaged MMAD across all combinations ranged from 1.248 to 1.793 µm by the APS at a distance of 0.8 m away from the patient interface. Conclusions: Overall, the results highlight the potential for secondary inhalation of fugitive emissions released during simulated aerosol treatment with concurrent high-flow therapy. The findings will help in developing policy and best practice for risk mitigation from fugitive emissions.",2019 Jun 1,"['McGrath, James A.', 'O’Toole, Ciarraí', 'Bennett, Gavin', 'Joyce, Mary', 'Byrne, Miriam A.', 'MacLoughlin, Ronan']",Pharmaceutics,,,False
d6ea115f3fa7ea76715b04ee4a3f3a55add45397,PMC,Biological Function and Application of Picornaviral 2B Protein: A New Target for Antiviral Drug Development,http://dx.doi.org/10.3390/v11060510,PMC6630369,31167361,CC BY,"Picornaviruses are associated with acute and chronic diseases. The clinical manifestations of infections are often mild, but infections may also lead to respiratory symptoms, gastroenteritis, myocarditis, meningitis, hepatitis, and poliomyelitis, with serious impacts on human health and economic losses in animal husbandry. Thus far, research on picornaviruses has mainly focused on structural proteins such as VP1, whereas the non-structural protein 2B, which plays vital roles in the life cycle of the viruses and exhibits a viroporin or viroporin-like activity, has been overlooked. Viroporins are viral proteins containing at least one amphipathic α-helical structure, which oligomerizes to form transmembrane hydrophilic pores. In this review, we mainly summarize recent research data on the viroporin or viroporin-like activity of 2B proteins, which affects the biological function of the membrane, regulates cell death, and affects the host immune response. Considering these mechanisms, the potential application of the 2B protein as a candidate target for antiviral drug development is discussed, along with research challenges and prospects toward realizing a novel treatment strategy for picornavirus infections.",2019 Jun 4,"['Li, Zengbin', 'Zou, Zixiao', 'Jiang, Zeju', 'Huang, Xiaotian', 'Liu, Qiong']",Viruses,,,True
7531c4305658b8cf4fa576ae050d7162043fe535,PMC,Safety and Immunogenicity of a Novel Recombinant Simian Adenovirus ChAdOx2 as a Vectored Vaccine,http://dx.doi.org/10.3390/vaccines7020040,PMC6630572,31096710,CC BY,"Adenovirus vectored vaccines are a highly effective strategy to induce cellular immune responses which are particularly effective against intracellular pathogens. Recombinant simian adenovirus vectors were developed to circumvent the limitations imposed by the use of human adenoviruses due to widespread seroprevalence of neutralising antibodies. We have constructed a replication deficient simian adenovirus-vectored vaccine (ChAdOx2) expressing 4 genes from the Mycobacterium avium subspecies paratuberculosis (AhpC, Gsd, p12 and mpa). Safety and T-cell immunogenicity results of the first clinical use of the ChAdOx2 vector are presented here. The trial was conducted using a ‘three-plus-three’ dose escalation study design. We demonstrate the vaccine is safe, well tolerated and immunogenic.",2019 May 15,"['Folegatti, Pedro M.', 'Bellamy, Duncan', 'Roberts, Rachel', 'Powlson, Jonathan', 'Edwards, Nick J.', 'Mair, Catherine F.', 'Bowyer, Georgina', 'Poulton, Ian', 'Mitton, Celia H.', 'Green, Nicky', 'Berrie, Eleanor', 'Lawrie, Alison M.', 'Hill, Adrian V.S.', 'Ewer, Katie J.', 'Hermon-Taylor, John', 'Gilbert, Sarah C.']",Vaccines (Basel),,,True
3c65e846141b78b0c2cf685a1f68a1ea5fd6565e,PMC,Safety and Immunogenicity of a Novel Recombinant Simian Adenovirus ChAdOx2 as a Vectored Vaccine,http://dx.doi.org/10.3390/vaccines7020040,PMC6630572,31096710,CC BY,"Adenovirus vectored vaccines are a highly effective strategy to induce cellular immune responses which are particularly effective against intracellular pathogens. Recombinant simian adenovirus vectors were developed to circumvent the limitations imposed by the use of human adenoviruses due to widespread seroprevalence of neutralising antibodies. We have constructed a replication deficient simian adenovirus-vectored vaccine (ChAdOx2) expressing 4 genes from the Mycobacterium avium subspecies paratuberculosis (AhpC, Gsd, p12 and mpa). Safety and T-cell immunogenicity results of the first clinical use of the ChAdOx2 vector are presented here. The trial was conducted using a ‘three-plus-three’ dose escalation study design. We demonstrate the vaccine is safe, well tolerated and immunogenic.",2019 May 15,"['Folegatti, Pedro M.', 'Bellamy, Duncan', 'Roberts, Rachel', 'Powlson, Jonathan', 'Edwards, Nick J.', 'Mair, Catherine F.', 'Bowyer, Georgina', 'Poulton, Ian', 'Mitton, Celia H.', 'Green, Nicky', 'Berrie, Eleanor', 'Lawrie, Alison M.', 'Hill, Adrian V.S.', 'Ewer, Katie J.', 'Hermon-Taylor, John', 'Gilbert, Sarah C.']",Vaccines (Basel),,,False
a7c91b8fe16a943a9c53322b183bc2d867eef5cf,PMC,Serological Evidence of Influenza D Virus Circulation Among Cattle and Small Ruminants in France,http://dx.doi.org/10.3390/v11060516,PMC6630579,31195597,CC BY,"Influenza D virus (IDV) has first been identified in 2011 in the USA and was shown to mainly circulate in cattle. While IDV is associated with mild respiratory signs, its prevalence is still unknown. In the present study we show that IDV has been circulating throughout France in cattle and small ruminants, with 47.2% and 1.5% seropositivity, respectively. The high prevalence and moderate pathogenicity of IDV in cattle suggest that it may play an initiating role in the bovine respiratory disease complex.",2019 Jun 5,"['Oliva, Justine', 'Eichenbaum, Amit', 'Belin, Jade', 'Gaudino, Maria', 'Guillotin, Jean', 'Alzieu, Jean-Pierre', 'Nicollet, Philippe', 'Brugidou, Roland', 'Gueneau, Eric', 'Michel, Evelyne', 'Meyer, Gilles', 'Ducatez, Mariette F.']",Viruses,,,True
75e0588823ff9b1ec2f32b82dabf8414246f8851,PMC,Serological Evidence of Influenza D Virus Circulation Among Cattle and Small Ruminants in France,http://dx.doi.org/10.3390/v11060516,PMC6630579,31195597,CC BY,"Influenza D virus (IDV) has first been identified in 2011 in the USA and was shown to mainly circulate in cattle. While IDV is associated with mild respiratory signs, its prevalence is still unknown. In the present study we show that IDV has been circulating throughout France in cattle and small ruminants, with 47.2% and 1.5% seropositivity, respectively. The high prevalence and moderate pathogenicity of IDV in cattle suggest that it may play an initiating role in the bovine respiratory disease complex.",2019 Jun 5,"['Oliva, Justine', 'Eichenbaum, Amit', 'Belin, Jade', 'Gaudino, Maria', 'Guillotin, Jean', 'Alzieu, Jean-Pierre', 'Nicollet, Philippe', 'Brugidou, Roland', 'Gueneau, Eric', 'Michel, Evelyne', 'Meyer, Gilles', 'Ducatez, Mariette F.']",Viruses,,,False
2cbcfb658251f2d2873e1ec118deea4167283c0a,PMC,Cytolytic Perforin as an Adjuvant to Enhance the Immunogenicity of DNA Vaccines,http://dx.doi.org/10.3390/vaccines7020038,PMC6630607,31052178,CC BY,"DNA vaccines present one of the most cost-effective platforms to develop global vaccines, which have been tested for nearly three decades in preclinical and clinical settings with some success in the clinic. However, one of the major challenges for the development of DNA vaccines is their poor immunogenicity in humans, which has led to refinements in DNA delivery, dosage in prime/boost regimens and the inclusion of adjuvants to enhance their immunogenicity. In this review, we focus on adjuvants that can enhance the immunogenicity of DNA encoded antigens and highlight the development of a novel cytolytic DNA platform encoding a truncated mouse perforin. The application of this innovative DNA technology has considerable potential in the development of effective vaccines.",2019 Apr 30,"['Shrestha, Ashish C.', 'Wijesundara, Danushka K.', 'Masavuli, Makutiro G.', 'Mekonnen, Zelalem A.', 'Gowans, Eric J.', 'Grubor-Bauk, Branka']",Vaccines (Basel),,,True
a07e1b3380d19de30b382b8d64c6c820965e8091,PMC,Bafilomycin A1 and U18666A Efficiently Impair ZIKV Infection,http://dx.doi.org/10.3390/v11060524,PMC6630673,31174294,CC BY,"Zika virus (ZIKV) is a highly transmissive virus that belongs to the Flaviviridae family, which comprises several other pathogens that threaten human health. This re-emerging virus gained attention during the outbreak in Brazil in 2016, where a considerable number of microcephaly cases in newborns was associated with ZIKV infection during pregnancy. Lacking a preventive vaccine or antiviral drugs, efforts have been made to better understand the viral life cycle. In light of this, the relevance of the endosomal–lysosomal compartment for the ZIKV life cycle was investigated. A549 and SH-SY5Y cells were infected with either the African strain (associated with mild symptoms) or the French Polynesia strain (associated with neurological complications). For both strains, the V-ATPase inhibitor, bafilomycin A1, efficiently inhibited ZIKV entry and prevented the spread of the infection by interfering with viral maturation. Additionally, affecting cholesterol metabolism and transport with the drug U18666A, which inactivates late endosomes and lysosomes, impairs the viral life cycle. The data presented show a clear antiviral effect of two compounds that target the same compartments in different ways. This highlights the relevance of the endosomal–lysosomal compartment for the viral life cycle that should be considered as a target for antivirals.",2019 Jun 6,"['Sabino, Catarina', 'Basic, Michael', 'Bender, Daniela', 'Elgner, Fabian', 'Himmelsbach, Kiyoshi', 'Hildt, Eberhard']",Viruses,,,True
b59cd56c099998c01ab1755c6723f88abeffeecf,PMC,Bafilomycin A1 and U18666A Efficiently Impair ZIKV Infection,http://dx.doi.org/10.3390/v11060524,PMC6630673,31174294,CC BY,"Zika virus (ZIKV) is a highly transmissive virus that belongs to the Flaviviridae family, which comprises several other pathogens that threaten human health. This re-emerging virus gained attention during the outbreak in Brazil in 2016, where a considerable number of microcephaly cases in newborns was associated with ZIKV infection during pregnancy. Lacking a preventive vaccine or antiviral drugs, efforts have been made to better understand the viral life cycle. In light of this, the relevance of the endosomal–lysosomal compartment for the ZIKV life cycle was investigated. A549 and SH-SY5Y cells were infected with either the African strain (associated with mild symptoms) or the French Polynesia strain (associated with neurological complications). For both strains, the V-ATPase inhibitor, bafilomycin A1, efficiently inhibited ZIKV entry and prevented the spread of the infection by interfering with viral maturation. Additionally, affecting cholesterol metabolism and transport with the drug U18666A, which inactivates late endosomes and lysosomes, impairs the viral life cycle. The data presented show a clear antiviral effect of two compounds that target the same compartments in different ways. This highlights the relevance of the endosomal–lysosomal compartment for the viral life cycle that should be considered as a target for antivirals.",2019 Jun 6,"['Sabino, Catarina', 'Basic, Michael', 'Bender, Daniela', 'Elgner, Fabian', 'Himmelsbach, Kiyoshi', 'Hildt, Eberhard']",Viruses,,,False
0f45da571ca739a0ec5c818fa2d39025398673d7,PMC,Seoul Virus Tropism and Pathology in Naturally Infected Feeder Rats,http://dx.doi.org/10.3390/v11060531,PMC6630879,31181690,CC BY,"Seoul virus (SEOV) is a zoonotic orthohantavirus carried by black and brown rats, and can cause hemorrhagic fever with renal syndrome in humans. Human cases of SEOV virus infection have most recently been reported in the USA, United Kingdom, France and the Netherlands and were primarily associated with contact with pet rats and feeder rats. Infection of rats results in an asymptomatic but persistent infection. Little is known about the cell tropism of SEOV in its reservoir and most available data is based on experimental infection studies in which rats were inoculated via a route which does not recapitulate virus transmission in nature. Here we report the histopathological analysis of SEOV cell tropism in key target organs following natural infection of a cohort of feeder rats, comprising 19 adults and 11 juveniles. All adult rats in this study were positive for SEOV specific antibodies and viral RNA in their tissues. One juvenile rat was seropositive, but negative in the rRT-PCR. Of the 19 adult rats of which subsequently additional organs were tested, SEOV RNA was detected in all lungs, followed by kidney (79%) and liver (74%). Histopathologic changes associated with SEOV infection were primarily found in the liver, consistent with a pathological diagnosis of a mild hepatitis. In conclusion, natural SEOV infection results in mild inflammation of the liver in the absence of clinical disease.",2019 Jun 7,"['Maas, Miriam', 'van Heteren, Melanie', 'de Vries, Ankje', 'Kuiken, Thijs', 'Hoornweg, Tabitha', 'Veldhuis Kroeze, Edwin', 'Rockx, Barry']",Viruses,,,True
75af9aa0e63889abde2eedaf0e41738b8ab082df,PMC,Current and Novel Approaches in Influenza Management,http://dx.doi.org/10.3390/vaccines7020053,PMC6630949,31216759,CC BY,"Influenza is a disease that poses a significant health burden worldwide. Vaccination is the best way to prevent influenza virus infections. However, conventional vaccines are only effective for a short period of time due to the propensity of influenza viruses to undergo antigenic drift and antigenic shift. The efficacy of these vaccines is uncertain from year-to-year due to potential mismatch between the circulating viruses and vaccine strains, and mutations arising due to egg adaptation. Subsequently, the inability to store these vaccines long-term and vaccine shortages are challenges that need to be overcome. Conventional vaccines also have variable efficacies for certain populations, including the young, old, and immunocompromised. This warrants for diverse efficacious vaccine developmental approaches, involving both active and passive immunization. As opposed to active immunization platforms (requiring the use of whole or portions of pathogens as vaccines), the rapidly developing passive immunization involves administration of either pathogen-specific or broadly acting antibodies against a kind or class of pathogens as a treatment to corresponding acute infection. Several antibodies with broadly acting capacities have been discovered that may serve as means to suppress influenza viral infection and allow the process of natural immunity to engage opsonized pathogens whilst boosting immune system by antibody-dependent mechanisms that bridge the innate and adaptive arms. By that; passive immunotherapeutics approach assumes a robust tool that could aid control of influenza viruses. In this review, we comment on some improvements in influenza management and promising vaccine development platforms with an emphasis on the protective capacity of passive immunotherapeutics especially when coupled with the use of antivirals in the management of influenza infection.",2019 Jun 18,"['Kotey, Erasmus', 'Lukosaityte, Deimante', 'Quaye, Osbourne', 'Ampofo, William', 'Awandare, Gordon', 'Iqbal, Munir']",Vaccines (Basel),,,True
629a7c48e6c7c91265533e47a8e7f3afe54cbc4a,PMC,Animal Virus Ecology and Evolution Are Shaped by the Virus Host-Body Infiltration and Colonization Pattern,http://dx.doi.org/10.3390/pathogens8020072,PMC6631033,31130619,CC BY,"The current classification of animal viruses is largely based on the virus molecular world. Less attention is given to why and how virus fitness results from the success of virus transmission. Virus transmission reflects the infection-shedding-transmission dynamics, and with it, the organ system involvement and other, macroscopic dimensions of the host environment. This study describes the transmission ecology of the world main livestock viruses, 36 in total, a mix of RNA, DNA and retroviruses. Following an iterative process, the viruses are virtually ranked in an outer- to inner-body fashion, by organ system, on ecological grounds. Also portrayed are the shifts in virus host tropism and virus genome. The synthesis of the findings reveals a predictive virus evolution framework, based on the outer- to inner-body changes in the interplay of host environment-transmission modes-organ system involvement-host cell infection cycle-virus genome. Outer-body viruses opportunistically respond to the variation in the external environment. For example, respiratory and enteric viruses tend to be associated with poultry and pig mass rearing. Ruminant and equine viruses tend to be more deep-rooted and host-specific, and also establish themselves in the vital inner-body systems. It is concluded that the framework may assist the study of new emerging viruses and pandemic risks.",2019 May 25,"Slingenbergh, Jan",Pathogens,,,True
43d98a92044a0de6683fc54fb2b5694a828856d7,PMC,Mammalian orthoreovirus Infection is Enhanced in Cells Pre-Treated with Sodium Arsenite,http://dx.doi.org/10.3390/v11060563,PMC6631071,31216693,CC BY,"Following reovirus infection, cells activate stress responses that repress canonical translation as a mechanism to limit progeny virion production. Work by others suggests that these stress responses, which are part of the integrated stress response (ISR), may benefit rather than repress reovirus replication. Here, we report that compared to untreated cells, treating cells with sodium arsenite (SA) to activate the ISR prior to infection enhanced viral protein expression, percent infectivity, and viral titer. SA-mediated enhancement was not strain-specific, but was cell-type specific. While SA pre-treatment of cells offered the greatest enhancement, treatment within the first 4 h of infection increased the percent of cells infected. SA activates the heme-regulated eIF2α (HRI) kinase, which phosphorylates eukaryotic translation initiation factor 2 alpha (eIF2α) to induce stress granule (SG) formation. Heat shock (HS), another activator of HRI, also induced eIF2α phosphorylation and SGs in cells. However, HS had no effect on percent infectivity or viral yield but did enhance viral protein expression. These data suggest that SA pre-treatment perturbs the cell in a way that is beneficial for reovirus and that this enhancement is independent of SG induction. Understanding how to manipulate the cellular stress responses during infection to enhance replication could help to maximize the oncolytic potential of reovirus.",2019 Jun 18,"['Lutz, Michael M.', 'Worth, Megan P.', 'Hinchman, Meleana M.', 'Parker, John S.L.', 'Ledgerwood, Emily D.']",Viruses,,,True
4cac1c7be02b644903d462fa3a0f6c56d8726d2b,PMC,Mammalian orthoreovirus Infection is Enhanced in Cells Pre-Treated with Sodium Arsenite,http://dx.doi.org/10.3390/v11060563,PMC6631071,31216693,CC BY,"Following reovirus infection, cells activate stress responses that repress canonical translation as a mechanism to limit progeny virion production. Work by others suggests that these stress responses, which are part of the integrated stress response (ISR), may benefit rather than repress reovirus replication. Here, we report that compared to untreated cells, treating cells with sodium arsenite (SA) to activate the ISR prior to infection enhanced viral protein expression, percent infectivity, and viral titer. SA-mediated enhancement was not strain-specific, but was cell-type specific. While SA pre-treatment of cells offered the greatest enhancement, treatment within the first 4 h of infection increased the percent of cells infected. SA activates the heme-regulated eIF2α (HRI) kinase, which phosphorylates eukaryotic translation initiation factor 2 alpha (eIF2α) to induce stress granule (SG) formation. Heat shock (HS), another activator of HRI, also induced eIF2α phosphorylation and SGs in cells. However, HS had no effect on percent infectivity or viral yield but did enhance viral protein expression. These data suggest that SA pre-treatment perturbs the cell in a way that is beneficial for reovirus and that this enhancement is independent of SG induction. Understanding how to manipulate the cellular stress responses during infection to enhance replication could help to maximize the oncolytic potential of reovirus.",2019 Jun 18,"['Lutz, Michael M.', 'Worth, Megan P.', 'Hinchman, Meleana M.', 'Parker, John S.L.', 'Ledgerwood, Emily D.']",Viruses,,,False
6673835e81ea115480bd68bc4e2d90c742bb77c1,PMC,Susceptibility of Chickens to Porcine Deltacoronavirus Infection,http://dx.doi.org/10.3390/v11060573,PMC6631122,31234434,CC BY,"Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus with worldwide distribution. PDCoV belongs to the Deltacoronavirus (DCoV) genus, which mainly includes avian coronaviruses (CoVs). PDCoV has the potential to infect human and chicken cells in vitro, and also has limited infectivity in calves. However, the origin of PDCoV in pigs, the host range, and cross-species infection of PDCoV still remain unclear. To determine whether PDCoV really has the ability to infect chickens in vivo, the three lines of chicken embryos and specific pathogen free (SPF) chickens were inoculated with PDCoV HNZK-02 strain to investigate PDCoV infection in the current study. Our results indicated that PDCoV can infect chicken embryos and could be continuously passaged on them. Furthermore, we observed that PDCoV-inoculated chickens showed mild diarrhea symptoms and low fecal viral RNA shedding. PDCoV RNA could also be detected in multiple organs (lung, kidney, jejunum, cecum, and rectum) and intestinal contents of PDCoV-inoculated chickens until 17 day post-inoculation by real-time quantitative PCR (qRT-PCR). A histology analysis indicated that PDCoV caused mild lesions in the lung, kidney, and intestinal tissues. These results prove the susceptibility of chickens to PDCoV infection, which might provide more insight about the cross-species transmission of PDCoV.",2019 Jun 21,"['Liang, Qingqing', 'Zhang, Honglei', 'Li, Bingxiao', 'Ding, Qingwen', 'Wang, Yabin', 'Gao, Wenming', 'Guo, Donghui', 'Wei, Zhanyong', 'Hu, Hui']",Viruses,,,True
9ee05def9e9c177e9c22bf4ef9bfcca045572916,PMC,Computational Approaches and Challenges to Developing Universal Influenza Vaccines,http://dx.doi.org/10.3390/vaccines7020045,PMC6631137,31141933,CC BY,"The traditional design of effective vaccines for rapidly-evolving pathogens, such as influenza A virus, has failed to provide broad spectrum and long-lasting protection. With low cost whole genome sequencing technology and powerful computing capabilities, novel computational approaches have demonstrated the potential to facilitate the design of a universal influenza vaccine. However, few studies have integrated computational optimization in the design and discovery of new vaccines. Understanding the potential of computational vaccine design is necessary before these approaches can be implemented on a broad scale. This review summarizes some promising computational approaches under current development, including computationally optimized broadly reactive antigens with consensus sequences, phylogenetic model-based ancestral sequence reconstruction, and immunomics to compute conserved cross-reactive T-cell epitopes. Interactions between virus-host-environment determine the evolvability of the influenza population. We propose that with the development of novel technologies that allow the integration of data sources such as protein structural modeling, host antibody repertoire analysis and advanced phylodynamic modeling, computational approaches will be crucial for the development of a long-lasting universal influenza vaccine. Taken together, computational approaches are powerful and promising tools for the development of a universal influenza vaccine with durable and broad protection.",2019 May 28,"['Qiu, Xueting', 'Duvvuri, Venkata R.', 'Bahl, Justin']",Vaccines (Basel),,,True
17a5402664095260470c65dee52c38311b3ea399,PMC,Policy and Science for Global Health Security: Shaping the Course of International Health,http://dx.doi.org/10.3390/tropicalmed4020060,PMC6631183,30974815,CC BY,"The global burden of infectious diseases and the increased attention to natural, accidental, and deliberate biological threats has resulted in significant investment in infectious disease research. Translating the results of these studies to inform prevention, detection, and response efforts often can be challenging, especially if prior relationships and communications have not been established with decision-makers. Whatever scientific information is shared with decision-makers before, during, and after public health emergencies is highly dependent on the individuals or organizations who are communicating with policy-makers. This article briefly describes the landscape of stakeholders involved in information-sharing before and during emergencies. We identify critical gaps in translation of scientific expertise and results, and biosafety and biosecurity measures to public health policy and practice with a focus on One Health and zoonotic diseases. Finally, we conclude by exploring ways of improving communication and funding, both of which help to address the identified gaps. By leveraging existing scientific information (from both the natural and social sciences) in the public health decision-making process, large-scale outbreaks may be averted even in low-income countries.",2019 Apr 10,"['Berger, Kavita M.', 'Wood, James L. N.', 'Jenkins, Bonnie', 'Olsen, Jennifer', 'Morse, Stephen S.', 'Gresham, Louise', 'Root, J. Jeffrey', 'Rush, Margaret', 'Pigott, David', 'Winkleman, Taylor', 'Moore, Melinda', 'Gillespie, Thomas R.', 'Nuzzo, Jennifer B.', 'Han, Barbara A.', 'Olinger, Patricia', 'Karesh, William B.', 'Mills, James N.', 'Annelli, Joseph F.', 'Barnabei, Jamie', 'Lucey, Daniel', 'Hayman, David T. S.']",Trop Med Infect Dis,,,True
af92c6b29f579151999d766c4208146088aa12c6,PMC,Cholesterol-25-hydroxylase Is a Chicken ISG That Restricts ALV-J Infection by Producing 25-hydroxycholesterol,http://dx.doi.org/10.3390/v11060498,PMC6631237,31151272,CC BY,"The avian leukosis virus subgroup J (ALV-J) belongs to the chicken retrovirus that causes enormous economic losses in the poultry industry. Interferon-stimulated genes (ISGs) are critical for controlling virus infections. Here, we identified 897 type I ISGs induced by interferon-α (IFN-α) in chicken peripheral blood mononuclear cell (PBMC) by RNA-Seq. In addition, we further identified 152 potential anti-ALV-J chicken type I ISGs. Among these potential anti-ALV-J ISGs, chicken cholesterol 25-hydroxylase (chCH25H) was selected for further antiviral mechanism studies in chicken embryo fibroblast cell lines (DF1). The gene chCH25H is located on chromosome 6 and clustered in a distinct group with mammals CH25H in the phylogenetic tree. The core promoter region of chCH25H was located within −75/−1 sequence. We found that chCH25H was induced by chicken IFN-α and ALV-J in DF1 cells. The overexpression of chCH25H significantly inhibited ALV-J replication in DF1 cells at 48 h post infection (hpi). In addition, ALV-J replication was significantly enhanced in the chCH25H- knockout DF1 cells. Furthermore, we demonstrated that chCH25H restricted ALV-J infection through the production of 25-hydroxycholesterol (25HC), rather than type I and II interferon. Our results identified 152 potential anti-ALV-J chicken type I ISGs and revealed that 25HC, the product of chCH25H, could be used as a natural antiviral agent to control ALV-J infection.",2019 May 30,"['Xie, Tingting', 'Feng, Min', 'Dai, Manman', 'Mo, Guodong', 'Ruan, Zhuohao', 'Wang, Guiyan', 'Shi, Meiqing', 'Zhang, Xiquan']",Viruses,,,True
9bbe789148466f6667a673885d4adddedf6b74e4,PMC,Isolation of a Divergent Strain of Bovine Parainfluenza Virus Type 3 (BPIV3) Infecting Cattle in China,http://dx.doi.org/10.3390/v11060489,PMC6631270,31146368,CC BY,"Bovine parainfluenza virus type 3 (BPIV3) is one of the most important known viral respiratory pathogens of both young and adult cattle. It is also named “heat stress in transport”, causing morbidity and mass death. New variants of BPIV3 have been detected or isolated in China since 2008. Here, we isolate one BPIV3 strain (named BPIV3 BJ) in Madin-Darby bovine kidney (MDBK) cells from nasal samples collected in China. Phylogenetic analysis showed that our isolate is related to BPIV3 of the genotype A. The comparison of BPIV3-BJ and the reference Chinese isolate NM09 showed that these strains are highly divergent. We found many differences in the amino acid composition in the nucleocapsid (NP) protein among these genotype A strains. Since the NP protein has been implicated in immunization studies, our BPIV3 isolate will be useful for the development of immune assays and vaccine studies. The diversity of BPIV3 lineages that we found in China indicated ongoing evolution for immune escape. Our study highlights the importance of genetic surveillance for determining the effect of BPIV3 variability on pathogen evolution and population-scale immunity.",2019 May 29,"['Leal, Élcio', 'Liu, Cun', 'Zhao, Zhanzhong', 'Deng, Yong', 'Villanova, Fabiola', 'Liang, Lin', 'Li, Jinxiang', 'Cui, Shangjin']",Viruses,,,True
ebbcdd0881f10295cb8588179e187cc35f93871b,PMC,Isolation of a Divergent Strain of Bovine Parainfluenza Virus Type 3 (BPIV3) Infecting Cattle in China,http://dx.doi.org/10.3390/v11060489,PMC6631270,31146368,CC BY,"Bovine parainfluenza virus type 3 (BPIV3) is one of the most important known viral respiratory pathogens of both young and adult cattle. It is also named “heat stress in transport”, causing morbidity and mass death. New variants of BPIV3 have been detected or isolated in China since 2008. Here, we isolate one BPIV3 strain (named BPIV3 BJ) in Madin-Darby bovine kidney (MDBK) cells from nasal samples collected in China. Phylogenetic analysis showed that our isolate is related to BPIV3 of the genotype A. The comparison of BPIV3-BJ and the reference Chinese isolate NM09 showed that these strains are highly divergent. We found many differences in the amino acid composition in the nucleocapsid (NP) protein among these genotype A strains. Since the NP protein has been implicated in immunization studies, our BPIV3 isolate will be useful for the development of immune assays and vaccine studies. The diversity of BPIV3 lineages that we found in China indicated ongoing evolution for immune escape. Our study highlights the importance of genetic surveillance for determining the effect of BPIV3 variability on pathogen evolution and population-scale immunity.",2019 May 29,"['Leal, Élcio', 'Liu, Cun', 'Zhao, Zhanzhong', 'Deng, Yong', 'Villanova, Fabiola', 'Liang, Lin', 'Li, Jinxiang', 'Cui, Shangjin']",Viruses,,,False
b8e929a5f023a12cfe584678c9dc89cf2b8afc6e,PMC,Novel Picobirnaviruses in Respiratory and Alimentary Tracts of Cattle and Monkeys with Large Intra- and Inter-Host Diversity,http://dx.doi.org/10.3390/v11060574,PMC6631280,31234565,CC BY,"Picobirnaviruses (PBVs) are mostly found in animal alimentary samples. In this study, among 576 respiratory specimens from 476 mammals and 100 chickens, genogroup I PBVs were detected in three cattle and three monkeys, and a genogroup II PBV-positive sample was collected from one cattle specimen. More than one PBV sequence type was observed in two and one genogroup I PBV-positive samples from cattle and monkeys, respectively. Twenty-four complete/near-complete segments 2 (nine from respiratory and 15 from alimentary samples) from the cattle and monkey genogroup I PBVs and one complete segment 2 from the cattle genogroup II PBV were sequenced. Similar to other studies, the cattle PBVs also showed a high diversity. In contrast, the monkey PBVs observed in this study were clustered into three distinct clades. Within each clade, all the sequences showed >99% amino acid identities. This unique phenomenon is probably due to the fact that monkeys in our locality reside in separated troops with minimal inter-troop contact.",2019 Jun 23,"['Woo, Patrick C. Y.', 'Teng, Jade L. L.', 'Bai, Ru', 'Tang, Ying', 'Wong, Annette Y. P.', 'Li, Kenneth S. M.', 'Lam, Carol S. F.', 'Fan, Rachel Y. Y.', 'Lau, Susanna K. P.', 'Yuen, Kwok-Yung']",Viruses,,,True
b5b87074a3f33c0a1408a01218e1776ae85f5b31,PMC,"The Mechanism of Action of Ursolic Acid as a Potential Anti-Toxoplasmosis Agent, and Its Immunomodulatory Effects",http://dx.doi.org/10.3390/pathogens8020061,PMC6631288,31075881,CC BY,"This study was performed to investigate the mechanism of action of ursolic acid in terms of anti-Toxoplasma gondii effects, including immunomodulatory effects. We evaluated the anti-T. gondii effects of ursolic acid, and analyzed the production of nitric oxide (NO), reactive oxygen species (ROS), and cytokines through co-cultured immune cells, as well as the expression of intracellular organelles of T. gondii. The subcellular organelles and granules of T. gondii, particularly rhoptry protein 18, microneme protein 8, and inner membrane complex sub-compartment protein 3, were markedly decreased when T. gondii was treated with ursolic acid, and their expressions were effectively inhibited. Furthermore, ursolic acid effectively increased the production of NO, ROS, interleukin (IL)-10, IL-12, granulocyte macrophage colony stimulating factor (GM-CSF), and interferon-β, while reducing the expression of IL-1β, IL-6, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1 (TGF-β1) in T. gondii-infected immune cells. These results demonstrate that ursolic acid not only causes anti-T. gondii activity/action by effectively inhibiting the survival of T. gondii and the subcellular organelles of T. gondii, but also induces specific immunomodulatory effects in T. gondii-infected immune cells. Therefore, this study indicates that ursolic acid can be effectively utilized as a potential candidate agent for developing novel anti-toxoplasmosis drugs, and has immunomodulatory activity.",2019 May 9,"['Choi, Won Hyung', 'Lee, In Ah']",Pathogens,,,True
8b27b57e5226ffb254f5d747bf115690e2c73546,PMC,Evolutionary Dynamics in the RNA Bacteriophage Qβ Depends on the Pattern of Change in Selective Pressures,http://dx.doi.org/10.3390/pathogens8020080,PMC6631425,31216651,CC BY,"The rate of change in selective pressures is one of the main factors that determines the likelihood that populations can adapt to stress conditions. Generally, the reduction in the population size that accompanies abrupt environmental changes makes it difficult to generate and select adaptive mutations. However, in systems with high genetic diversity, as happens in RNA viruses, mutations with beneficial effects under new conditions can already be present in the population, facilitating adaptation. In this work, we have propagated an RNA bacteriophage (Qβ) at temperatures higher than the optimum, following different patterns of change. We have determined the fitness values and the consensus sequences of all lineages throughout the evolutionary process in order to establish correspondences between fitness variations and adaptive pathways. Our results show that populations subjected to a sudden temperature change gain fitness and fix mutations faster than those subjected to gradual changes, differing also in the particular selected mutations. The life-history of populations prior to the environmental change has great importance in the dynamics of adaptation. The conclusion is that in the bacteriophage Qβ, the standing genetic diversity together with the rate of temperature change determine both the rapidity of adaptation and the followed evolutionary pathways.",2019 Jun 18,"['Somovilla, Pilar', 'Manrubia, Susanna', 'Lázaro, Ester']",Pathogens,,,True
64504909cf5e7b5249b8c617c2d1973a3c301e85,PMC,20th International Conference on Emerging Infectious Diseases in the Pacific Rim Organized by the United States-Japan Cooperative Medical Sciences Program (USJCMSP),http://dx.doi.org/10.3390/vaccines7020035,PMC6631656,30987042,CC BY,"The 20th International Conference on Emerging Infectious Diseases in the Pacific Rim to3ok place in Shenzhen, China on January 8–9, 2018 followed by meetings of the acquired immunodeficiency syndrome (AIDS)/immunology, acute respiratory infections, cancer, hepatitis, and viral diseases panels on January 10–11. The conference was organized as part of the United States-Japan Cooperative Medical Sciences Program (USJCMSP) by the Japan Agency for Medical Research and Development (AMED) and the U.S. National Institutes of Health (NIH) and was locally hosted by the Shenzhen Third People’s Hospital and the Chinese Academy of Sciences (CAS) Institute of Microbiology. The conference provides the basis for networking and fostering of collaboration opportunities between researchers in Southeast Asia and the United States based on the scientific and interactive platform of the USJCMSP and takes place in the region on an annual basis. This report summarizes the discussions and conclusions from the conference.",2019 Apr 2,"[None, 'Bernabe, K. Gayle', 'Lu, Kristina T.', 'Handley, F. Gray', 'Griffin, Diane E.', 'Kurane, Ichiro', 'Iwamoto, Aikichi', 'Gao, George F.', 'Krammer, Florian']",Vaccines (Basel),,,True
e9a9765d57cbca2e0c985f6fdcd04de38b0384cf,PMC,Prevalence of porcine circovirus type 3 in pigs in the southeastern Chinese province of Zhejiang,http://dx.doi.org/10.1186/s12917-019-1977-7,PMC6631677,31307451,CC BY,"BACKGROUND: Porcine circovirus type 3 (PCV3) was first reported in US in 2016. The virus was also identified later in China. Prevalence of PCV3 in Zhejiang province in southeastern China is not clear though it has been reported in many parts of China. RESULTS: PCV3 infection and its co-infection with other swine viral pathogens in pig herds of Zhejiang province were retrospectively investigated by quantitative PCR (qPCR) and its sero-prevalence by indirect ELISA. PCV3 was found positive in 67.1% of the 283 clinical samples taken from 2014 to 2017 as shown by qPCR. Single infection with PCV3 accounted for only one-third of the samples, and majority were of co-infections, predominantly with PEDV (41.6%) but generally low with other swine viruses. Indirect ELISA using the PCV3 capsid protein as the coating antigen revealed an average sero-positive rate of 52.6% (40.8 to 60.8%) in 2345 serum samples from 2011 to 2017, with earliest yet high positive findings in samples taken in 2012. Of 203 serum samples, the qPCR method showed more positive findings than ELISA (81.3% vs 56.2%). With 89 serum samples negative by ELISA, vast majority (n = 81) were found positive by qPCR. There was negative correlation in levels of PCV3 DNA and anti-capsid antibody response. ORF2-based phylogenetic analysis revealed three major groups (PCV3a, PCV3b and PCV3c) of the 200 strains, 38 from this study and 162 reference strains from GenBank. Most of the strains from this study were clustered into PCV3c. Of the putative signature residues of the capsid protein (aa 24, 27, 77 and 150) relative to the three groups, only the PCV3a group strains showed a distinct pattern of residues VKSI (95% of the strains), while the other two groups did not have such a ‘signature’ pattern. CONCLUSIONS: Results from this study provided further evidence that the novel virus PCV3 was widely distributed in China and might have emerged in Zhejiang province before 2014, most probably back in 2012 when there was high PCV3 sero-prevalence. PCV3 might be viremic in pigs and could spread by fecal shedding. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-019-1977-7) contains supplementary material, which is available to authorized users.",2019 Jul 15,"['Geng, Shichao', 'Luo, Hao', 'Liu, Yajie', 'Chen, Cong', 'Xu, Weicheng', 'Chen, Yunlu', 'Li, Xiaoliang', 'Fang, Weihuan']",BMC Vet Res,,,True
a16aeee3d8878ab6dd536c418742d58b946b4699,PMC,A Comparison of Plasmid DNA and mRNA as Vaccine Technologies,http://dx.doi.org/10.3390/vaccines7020037,PMC6631684,31022829,CC BY,"This review provides a comparison of the theoretical issues and experimental findings for plasmid DNA and mRNA vaccine technologies. While both have been under development since the 1990s, in recent years, significant excitement has turned to mRNA despite the licensure of several veterinary DNA vaccines. Both have required efforts to increase their potency either via manipulating the plasmid DNA and the mRNA directly or through the addition of adjuvants or immunomodulators as well as delivery systems and formulations. The greater inherent inflammatory nature of the mRNA vaccines is discussed for both its potential immunological utility for vaccines and for the potential toxicity. The status of the clinical trials of mRNA vaccines is described along with a comparison to DNA vaccines, specifically the immunogenicity of both licensed veterinary DNA vaccines and select DNA vaccine candidates in human clinical trials.",2019 Apr 24,"Liu, Margaret A.",Vaccines (Basel),,,True
40847cd029d6f68acbb579f47f3635fee5c23b48,PMC,Recent Advances in Droplet-based Microfluidic Technologies for Biochemistry and Molecular Biology,http://dx.doi.org/10.3390/mi10060412,PMC6631694,31226819,CC BY,"Recently, droplet-based microfluidic systems have been widely used in various biochemical and molecular biological assays. Since this platform technique allows manipulation of large amounts of data and also provides absolute accuracy in comparison to conventional bioanalytical approaches, over the last decade a range of basic biochemical and molecular biological operations have been transferred to drop-based microfluidic formats. In this review, we introduce recent advances and examples of droplet-based microfluidic techniques that have been applied in biochemistry and molecular biology research including genomics, proteomics and cellomics. Their advantages and weaknesses in various applications are also comprehensively discussed here. The purpose of this review is to provide a new point of view and current status in droplet-based microfluidics to biochemists and molecular biologists. We hope that this review will accelerate communications between researchers who are working in droplet-based microfluidics, biochemistry and molecular biology.",2019 Jun 20,"['Sánchez Barea, Joel', 'Lee, Juhwa', 'Kang, Dong-Ku']",Micromachines (Basel),,,True
73de62f8272982125df5a376a10f99267968c6e4,PMC,Hepatitis E Virus Drug Development,http://dx.doi.org/10.3390/v11060485,PMC6631701,31141919,CC BY,"Hepatitis E virus (HEV) is an underestimated disease, leading to estimated 20 million infections and up to 70,000 deaths annually. Infections are mostly asymptomatic but can reach mortality rates up to 25% in pregnant women or become chronic in immunocompromised patients. The current therapy options are limited to the unspecific antivirals Ribavirin (RBV) and pegylated Interferon-α (pegIFN-α). RBV leads to viral clearance in only 80% of patients treated, and is, similar to pegIFN-α, contraindicated in the major risk group of pregnant women, emphasizing the importance of new therapy options. In this review, we focus on the urgent need and current efforts in HEV drug development. We provide an overview of the current status of HEV antiviral research. Furthermore, we discuss strategies for drug development and the limitations of the approaches with respect to HEV.",2019 May 28,"['Kinast, Volker', 'Burkard, Thomas L', 'Todt, Daniel', 'Steinmann, Eike']",Viruses,,,True
fcf74132e357aaadf7be22016a76d437664db797,PMC,Lipid Metabolism as a Source of Druggable Targets for Antiviral Discovery against Zika and Other Flaviviruses,http://dx.doi.org/10.3390/ph12020097,PMC6631711,31234348,CC BY,"The Zika virus (ZIKV) is a mosquito-borne flavivirus that can lead to birth defects (microcephaly), ocular lesions and neurological disorders (Guillain-Barré syndrome). There is no licensed vaccine or antiviral treatment against ZIKV infection. The effort to understand the complex interactions of ZIKV with cellular networks contributes to the identification of novel host-directed antiviral (HDA) candidates. Among the cellular pathways involved in infection, lipid metabolism gains attention. In ZIKV-infected cells lipid metabolism attributed to intracellular membrane remodeling, virion morphogenesis, autophagy modulation, innate immunity and inflammation. The key roles played by the cellular structures associated with lipid metabolism, such as peroxisomes and lipid droplets, are starting to be deciphered. Consequently, there is a wide variety of lipid-related antiviral strategies that are currently under consideration, which include an inhibition of sterol regulatory element-binding proteins (SREBP), the activation of adenosine-monophosphate activated kinase (AMPK), an inhibition of acetyl-Coenzyme A carboxylase (ACC), interference with sphingolipid metabolism, blockage of intracellular cholesterol trafficking, or a treatment with cholesterol derivatives. Remarkably, most of the HDAs identified in these studies are also effective against flaviviruses other than ZIKV (West Nile virus and dengue virus), supporting their broad-spectrum effect. Considering that lipid metabolism is one of the main cellular pathways suitable for pharmacological intervention, the idea of repositioning drugs targeting lipid metabolism as antiviral candidates is gaining force.",2019 Jun 21,"['Martín-Acebes, Miguel A.', 'Jiménez de Oya, Nereida', 'Saiz, Juan-Carlos']",Pharmaceuticals (Basel),,,True
caacab8201dadba7c322aaebad07309ef12e3c93,PMC,Bacterial Outer Membrane Vesicles (OMVs)-Based Dual Vaccine for Influenza A H1N1 Virus and MERS-CoV,http://dx.doi.org/10.3390/vaccines7020046,PMC6631769,31141982,CC BY,"Vaccination is the most functional medical intervention to prophylactically control severe diseases caused by human-to-human or animal-to-human transmissible viral pathogens. Annually, seasonal influenza epidemics attack human populations leading to 290–650 thousand deaths/year worldwide. Recently, a novel Middle East Respiratory Syndrome Coronavirus emerged. Together, those two viruses present a significant public health burden in areas where they circulate. Herein, we generated a bacterial outer membrane vesicles (OMVs)-based vaccine presenting the antigenic stable chimeric fusion protein of the H1-type haemagglutinin (HA) of the pandemic influenza A virus (H1N1) strain from 2009 (H1N1pdm09) and the receptor binding domain (RBD) of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) (OMVs-H1/RBD). Our results showed that the chimeric antigen could induce specific neutralizing antibodies against both strains leading to protection of immunized mice against H1N1pdm09 and efficient neutralization of MERS-CoV. This study demonstrate that OMVs-based vaccines presenting viral antigens provide a safe and reliable approach to protect against two different viral infections.",2019 May 28,"['Shehata, Mahmoud M.', 'Mostafa, Ahmed', 'Teubner, Lisa', 'Mahmoud, Sara H.', 'Kandeil, Ahmed', 'Elshesheny, Rabeh', 'Boubak, Thamer A.', 'Frantz, Renate', 'Pietra, Luigi La', 'Pleschka, Stephan', 'Osman, Ahmed', 'Kayali, Ghazi', 'Chakraborty, Trinad', 'Ali, Mohamed A.', 'Mraheil, Mobarak Abu']",Vaccines (Basel),,,True
9153d6b8fb3af63f68f15f52198cdbc308c97333,PMC,IFITM3 Clusters on Virus Containing Endosomes and Lysosomes Early in the Influenza A Infection of Human Airway Epithelial Cells,http://dx.doi.org/10.3390/v11060548,PMC6631848,31212878,CC BY,"Interferon-induced transmembrane proteins (IFITMs) have been shown to strongly affect influenza A virus (IAV) infectivity in tissue culture. Moreover, polymorphisms in IFITM3 have been associated with the severity of the disease in humans. IFITM3 appears to act early in the infection, but its mechanism of action and potential interactions with incoming IAV structures are not yet defined. Here, we visualized endogenous IFITM3 interactions with IAV in the human lung epithelial cell line A549 and in primary human airway epithelial cells employing stimulated emission depletion super-resolution microscopy. By applying an iterative approach for the cluster definition and computational cluster analysis, we found that IFITM3 reorganizes into clusters as IAV infection progresses. IFITM3 cluster formation started at 2-3 h post infection and increased over time to finally coat IAV-containing endosomal vesicles. This IAV-induced phenotype was due to the endosomal recruitment of IFITM3 rather than to an overall increase in the IFITM3 abundance. While the IAV-induced IFITM3 clustering and localization to endosomal vesicles was comparable in primary human airway epithelial cells and the human lung epithelial cell line A549, the endogenous IFITM3 signal was higher in primary cells. Moreover, we observed IFITM3 signals adjacent to IAV-containing recycling endosomes.",2019 Jun 12,"['Kummer, Susann', 'Avinoam, Ori', 'Kräusslich, Hans-Georg']",Viruses,,,True
f5cc748972db45afa38ba6a335271e278a58554f,PMC,IFITM3 Clusters on Virus Containing Endosomes and Lysosomes Early in the Influenza A Infection of Human Airway Epithelial Cells,http://dx.doi.org/10.3390/v11060548,PMC6631848,31212878,CC BY,"Interferon-induced transmembrane proteins (IFITMs) have been shown to strongly affect influenza A virus (IAV) infectivity in tissue culture. Moreover, polymorphisms in IFITM3 have been associated with the severity of the disease in humans. IFITM3 appears to act early in the infection, but its mechanism of action and potential interactions with incoming IAV structures are not yet defined. Here, we visualized endogenous IFITM3 interactions with IAV in the human lung epithelial cell line A549 and in primary human airway epithelial cells employing stimulated emission depletion super-resolution microscopy. By applying an iterative approach for the cluster definition and computational cluster analysis, we found that IFITM3 reorganizes into clusters as IAV infection progresses. IFITM3 cluster formation started at 2-3 h post infection and increased over time to finally coat IAV-containing endosomal vesicles. This IAV-induced phenotype was due to the endosomal recruitment of IFITM3 rather than to an overall increase in the IFITM3 abundance. While the IAV-induced IFITM3 clustering and localization to endosomal vesicles was comparable in primary human airway epithelial cells and the human lung epithelial cell line A549, the endogenous IFITM3 signal was higher in primary cells. Moreover, we observed IFITM3 signals adjacent to IAV-containing recycling endosomes.",2019 Jun 12,"['Kummer, Susann', 'Avinoam, Ori', 'Kräusslich, Hans-Georg']",Viruses,,,False
33a39cbf4221c9373bc07bf09d325c066fbe97a0,PMC,Porcine Interferon Complex and Co-Evolution with Increasing Viral Pressure after Domestication,http://dx.doi.org/10.3390/v11060555,PMC6631851,31208045,CC BY,"Consisting of nearly 60 functional genes, porcine interferon (IFN)-complex represents an evolutionary surge of IFN evolution in domestic ungulate species. To compare with humans and mice, each of these species contains about 20 IFN functional genes, which are better characterized using the conventional IFN-α/β subtypes as examples. Porcine IFN-complex thus represents an optimal model for studying IFN evolution that resulted from increasing viral pressure during domestication and industrialization. We hypothesize and justify that porcine IFN-complex may extend its functionality in antiviral and immunomodulatory activity due to its superior molecular diversity. Furthermore, these unconventional IFNs could even confer some functional and signaling novelty beyond that of the well-studied IFN-α/β subtypes. Investigations into porcine IFN-complex will further our understanding of IFN biology and promote IFN-based therapeutic designs to confront swine viral diseases.",2019 Jun 15,"['Jennings, Jordan', 'Sang, Yongming']",Viruses,,,True
393091a75a8617bf9fd5127a834c16743a9e89cd,PMC,"Assessing the Potential Interactions between Cellular miRNA and Arboviral Genomic RNA in the Yellow Fever Mosquito, Aedes aegypti",http://dx.doi.org/10.3390/v11060540,PMC6631873,31185697,CC BY,"Although the role of exogenous small interfering RNA (siRNA) and P-element induced wimpy testis (PIWI)-interacting RNA (piRNA) pathways in mosquito antiviral immunity is increasingly better understood, there is still little knowledge regarding the role of mosquito cellular microRNA (miRNA). Identifying direct interactions between the mosquito miRNAs and the RNA genome of arboviruses and choosing the relevant miRNA candidates to explore resulting antiviral mechanisms are critical. Here, we carried out genomic analyses to identify Aedes aegypti miRNAs that potentially interact with various lineages and genotypes of chikungunya, dengue, and Zika viruses. By using prediction tools with distinct algorithms, several miRNA binding sites were commonly found within different genotypes/and or lineages of each arbovirus. We further analyzed those miRNAs that could target more than one arbovirus, required a low energy threshold to form miRNA-viralRNA (vRNA) complexes, and predicted potential RNA structures using RNAhybrid software. We predicted miRNA candidates that might participate in regulating arboviral replication in Ae. aegypti. Even without any experimental validation, which should be done as a next step, this study can shed further light on the role of miRNA in mosquito innate immunity and targets for future studies.",2019 Jun 10,"['Yen, Pei-Shi', 'Chen, Chun-Hong', 'Sreenu, Vattipally', 'Kohl, Alain', 'Failloux, Anna-Bella']",Viruses,,,True
3aeb4a0f6893b933dc061157d196e5618380c63b,PMC,Hypsugopoxvirus: A Novel Poxvirus Isolated from Hypsugo savii in Italy,http://dx.doi.org/10.3390/v11060568,PMC6631891,31248065,CC BY,"Interest in bat-related viruses has increased considerably during the last decade, leading to the discovery of a rising number of new viruses in several bat species. Poxviridae are a large, diverse family of DNA viruses that can infect a wide range of vertebrates and invertebrates. To date, only a few documented detections of poxviruses have been described in bat populations on three different continents (America, Africa, and Australia). These viruses are phylogenetically dissimilar and have diverse clinical impacts on their hosts. Herein, we report the isolation, nearly complete genome sequencing, and annotation of a novel poxvirus detected from an insectivorous bat (Hypsugo savii) in Northern Italy. The virus is tentatively named Hypsugopoxvirus (HYPV) after the bat species from which it was isolated. The nearly complete genome size is 166,600 nt and it encodes 161 genes. Genome analyses suggest that HYPV belongs to the Chordopoxvirinae subfamily, with the highest nucleotide identity (85%) to Eptesipoxvirus (EPTV) detected from a microbat Eptesicus fuscus in WA, USA, in 2011. To date, HYPV represents the first poxvirus detected in bats in Europe; thus, its viral ecology and disease associations should be investigated further.",2019 Jun 19,"['Lelli, Davide', 'Lavazza, Antonio', 'Prosperi, Alice', 'Sozzi, Enrica', 'Faccin, Francesca', 'Baioni, Laura', 'Trogu, Tiziana', 'Cavallari, Gian Luca', 'Mauri, Matteo', 'Gibellini, Anna Maria', 'Chiapponi, Chiara', 'Moreno, Ana']",Viruses,,,True
c04c85e7d1935bf71b5ccca3b9cb3fe3b68131d6,PMC,Novel Synthetic DNA Immunogens Targeting Latent Expressed Antigens of Epstein–Barr Virus Elicit Potent Cellular Responses and Inhibit Tumor Growth,http://dx.doi.org/10.3390/vaccines7020044,PMC6631996,31137606,CC BY,"Infectious diseases are linked to 15%–20% of cancers worldwide. Among them, Epstein–Barr virus (EBV) is an oncogenic herpesvirus that chronically infects over 90% of the adult population, with over 200,000 cases of cancer and 150,000 cancer-related deaths attributed to it yearly. Acute EBV infection can present as infectious mononucleosis, and lead to the future onset of multiple cancers, including Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. Many of these cancers express latent viral genes, including Epstein–Barr virus nuclear antigen 1 (EBNA1) and latent membrane proteins 1 and 2 (LMP1 and LMP2). Previous attempts to create potent immunogens against EBV have been reported but generated mixed success. We designed novel Synthetic Consensus (SynCon) DNA vaccines against EBNA1, LMP1 and LMP2 to improve on the immune potency targeting important antigens expressed in latently infected cells. These EBV tumor antigens are hypothesized to be useful targets for potential immunotherapy of EBV-driven cancers. We optimized the genetic sequences for these three antigens, studied them for expression, and examined their immune profiles in vivo. We observed that these immunogens generated unique profiles based on which antigen was delivered as the vaccine target. EBNA1vax and LMP2Avax generated the most robust T cell immunity. Interestingly, LMP1vax was a very weak immunogen, generating very low levels of CD8 T cell immunity both as a standalone vaccine and as part of a trivalent vaccine cocktail. LMP2Avax was able to drive immunity that impacted EBV-antigen-positive tumor growth. These studies suggest that engineered EBV latent protein vaccines deserve additional study as potential agents for immunotherapy of EBV-driven cancers.",2019 May 24,"['Wojtak, Krzysztof', 'Perales-Puchalt, Alfredo', 'Weiner, David B.']",Vaccines (Basel),,,True
cb7ddfb27c909da7c168e53cf6d056076094e8a5,PMC,Peptide-Protein Interaction Studies of Antimicrobial Peptides Targeting Middle East Respiratory Syndrome Coronavirus Spike Protein: An In Silico Approach,http://dx.doi.org/10.1155/2019/6815105,PMC6634063,31354813,CC BY,"There is no effective therapeutic or vaccine for Middle East Respiratory Syndrome and this study attempts to find therapy using peptide by establishing a basis for the peptide-protein interactions through in silico docking studies for the spike protein of MERS-CoV. The antimicrobial peptides (AMPs) were retrieved from the antimicrobial peptide database (APD3) and shortlisted based on certain important physicochemical properties. The binding mode of the shortlisted peptides was measured based on the number of clusters which forms in a protein-peptide docking using Piper. As a result, we identified a list of putative AMPs which binds to the spike protein of MERS-CoV, which may be crucial in providing the inhibitory action. It is observed that seven putative peptides have good binding score based on cluster size cutoff of 208. We conclude that seven peptides, namely, AP00225, AP00180, AP00549, AP00744, AP00729, AP00764, and AP00223, could possibly have binding with the active site of the MERS-CoV spike protein. These seven AMPs could serve as a therapeutic option for MERS and enhance its treatment outcome.",2019 Jul 1,"['Mustafa, Sabeena', 'Balkhy, Hanan', 'Gabere, Musa']",Adv Bioinformatics,,,False
30f0d89777ce7543d7b37544544c810b896c4821,PMC,Peptide-Protein Interaction Studies of Antimicrobial Peptides Targeting Middle East Respiratory Syndrome Coronavirus Spike Protein: An In Silico Approach,http://dx.doi.org/10.1155/2019/6815105,PMC6634063,31354813,CC BY,"There is no effective therapeutic or vaccine for Middle East Respiratory Syndrome and this study attempts to find therapy using peptide by establishing a basis for the peptide-protein interactions through in silico docking studies for the spike protein of MERS-CoV. The antimicrobial peptides (AMPs) were retrieved from the antimicrobial peptide database (APD3) and shortlisted based on certain important physicochemical properties. The binding mode of the shortlisted peptides was measured based on the number of clusters which forms in a protein-peptide docking using Piper. As a result, we identified a list of putative AMPs which binds to the spike protein of MERS-CoV, which may be crucial in providing the inhibitory action. It is observed that seven putative peptides have good binding score based on cluster size cutoff of 208. We conclude that seven peptides, namely, AP00225, AP00180, AP00549, AP00744, AP00729, AP00764, and AP00223, could possibly have binding with the active site of the MERS-CoV spike protein. These seven AMPs could serve as a therapeutic option for MERS and enhance its treatment outcome.",2019 Jul 1,"['Mustafa, Sabeena', 'Balkhy, Hanan', 'Gabere, Musa']",Adv Bioinformatics,,,True
a8557b122155d371bbf43c23abf059b526da6496,PMC,"Assessing the value of PCR assays in oral fluid samples for detecting African swine fever, classical swine fever, and foot-and-mouth disease in U.S. swine",http://dx.doi.org/10.1371/journal.pone.0219532,PMC6634402,31310643,CC0,"INTRODUCTION: Oral fluid sampling and testing offers a convenient, unobtrusive mechanism for evaluating the health status of swine, especially grower and finisher swine. This assessment evaluates the potential testing of oral fluid samples with real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) to detect African swine fever, classical swine fever, or foot-and-mouth disease for surveillance during a disease outbreak and early detection in a disease-free setting. METHODS: We used a series of logical arguments, informed assumptions, and a range of parameter values from literature and industry practices to examine the cost and value of information provided by oral fluid sampling and rRT-PCR testing for the swine foreign animal disease surveillance objectives outlined above. RESULTS: Based on the evaluation, oral fluid testing demonstrated value for both settings evaluated. The greatest value was in an outbreak scenario, where using oral fluids would minimize disruption of animal and farm activities, reduce sample sizes by 23%-40%, and decrease resource requirements relative to current individual animal sampling plans. For an early detection system, sampling every 3 days met the designed prevalence detection threshold with 0.95 probability, but was quite costly. LIMITATIONS: Implementation of oral fluid testing for African swine fever, classical swine fever, or foot-and-mouth disease surveillance is not yet possible due to several limitations and information gaps. The gaps include validation of PCR diagnostic protocols and kits for African swine fever, classical swine fever, or foot-and-mouth disease on swine oral fluid samples; minimal information on test performance in a field setting; detection windows with low virulence strains of some foreign animal disease viruses; and the need for confirmatory testing protocol development.",2019 Jul 16,"['Beemer, Oriana', 'Remmenga, Marta', 'Gustafson, Lori', 'Johnson, Kamina', 'Hsi, David', 'Antognoli, Maria Celia']",PLoS One,,,True
4e19f6204f9b71da1d578f07164ad58db49b8f92,PMC,Changes in cecal microbiota community of suckling piglets infected with porcine epidemic diarrhea virus,http://dx.doi.org/10.1371/journal.pone.0219868,PMC6634403,31310635,CC BY,"Diarrhea, caused by porcine epidemic diarrhea virus (PEDV), is a catastrophic gastrointestinal disease among suckling piglets, with high infectivity, morbidity, and mortality, causing huge economic losses to the pig industry. In the present study, we investigated the different microbiota from the cecal mucosa and cecal contents between healthy and PEDV-infected piglets. High-throughput 16S rRNA gene sequencing was performed to explore differences. The results revealed that microbial dysbiosis by PEDV infection occurred in the cecal mucosa and contents of suckling piglets at each microbial taxonomic level. The abundance of pathogenic bacteria associated with diseases, including diarrhea, was increased. The abundance of Fusobacterium was 26.71% and 33.91% in cecal mucosa and contents of PEDV-infected group, respectively, whereas that in the healthy groups was 17.85% and 9.88%. The proportion of Proteobacteria in the infected groups was relatively high (24.67% and 22.79%, respectively), whereas that in the healthy group was 13.13% and 11.34% in the cecal mucosa and contents, respectively. Additionally, the proportion of Bacteroidetes in the healthy group (29.89%, 37.32%) was approximately twice that of the PEDV-infected group (15.50%, 15.39%). “Nitrate reduction”, “Human pathogens diarrhea”, “Human pathogens gastroenteritis”, “Nitrite respiration”, and “Nitrite ammonification” were the enriched functional annotation terms in the PEDV-infected groups. Porcine epidemic diarrhea virus infection increased the proportion of harmful bacteria and decreased the proportion of beneficial bacteria in the cecal mucosa and contents of suckling piglets. Our findings suggest that determining the intestinal microbiota might provide a promising method to prevent PEDV and open a new avenue for future research.",2019 Jul 16,"['Tan, Zhen', 'Dong, Wanting', 'Ding, Yaqun', 'Ding, Xiangdong', 'Zhang, Qin', 'Jiang, Li']",PLoS One,,,True
7ddc27749844ce4dd2695ad282cc21c3f3629eec,PMC,The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling,http://dx.doi.org/10.7554/eLife.47117,PMC6634972,31309928,CC BY,"Symbiotic microbes impact the function and development of the central nervous system (CNS); however, little is known about the contribution of the microbiota during viral-induced neurologic damage. We identify that commensals aid in host defense following infection with a neurotropic virus through enhancing microglia function. Germfree mice or animals that receive antibiotics are unable to control viral replication within the brain leading to increased paralysis. Microglia derived from germfree or antibiotic-treated animals cannot stimulate viral-specific immunity and microglia depletion leads to worsened demyelination. Oral administration of toll-like receptor (TLR) ligands to virally infected germfree mice limits neurologic damage. Homeostatic activation of microglia is dependent on intrinsic signaling through TLR4, as disruption of TLR4 within microglia, but not the entire CNS (excluding microglia), leads to increased viral-induced clinical disease. This work demonstrates that gut immune-stimulatory products can influence microglia function to prevent CNS damage following viral infection.",,"['Brown, D Garrett', 'Soto, Raymond', 'Yandamuri, Soumya', 'Stone, Colleen', 'Dickey, Laura', 'Gomes-Neto, Joao Carlos', 'Pastuzyn, Elissa D', 'Bell, Rickesha', 'Petersen, Charisse', 'Buhrke, Kaitlin', 'Fujinami, Robert S', ""O'Connell, Ryan M"", 'Stephens, W Zac', 'Shepherd, Jason D', 'Lane, Thomas E', 'Round, June L']",eLife.; 8:e47117,,,True
90ddd17549311303aee9057ec807ed48609fe5cc,PMC,The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling,http://dx.doi.org/10.7554/eLife.47117,PMC6634972,31309928,CC BY,"Symbiotic microbes impact the function and development of the central nervous system (CNS); however, little is known about the contribution of the microbiota during viral-induced neurologic damage. We identify that commensals aid in host defense following infection with a neurotropic virus through enhancing microglia function. Germfree mice or animals that receive antibiotics are unable to control viral replication within the brain leading to increased paralysis. Microglia derived from germfree or antibiotic-treated animals cannot stimulate viral-specific immunity and microglia depletion leads to worsened demyelination. Oral administration of toll-like receptor (TLR) ligands to virally infected germfree mice limits neurologic damage. Homeostatic activation of microglia is dependent on intrinsic signaling through TLR4, as disruption of TLR4 within microglia, but not the entire CNS (excluding microglia), leads to increased viral-induced clinical disease. This work demonstrates that gut immune-stimulatory products can influence microglia function to prevent CNS damage following viral infection.",,"['Brown, D Garrett', 'Soto, Raymond', 'Yandamuri, Soumya', 'Stone, Colleen', 'Dickey, Laura', 'Gomes-Neto, Joao Carlos', 'Pastuzyn, Elissa D', 'Bell, Rickesha', 'Petersen, Charisse', 'Buhrke, Kaitlin', 'Fujinami, Robert S', ""O'Connell, Ryan M"", 'Stephens, W Zac', 'Shepherd, Jason D', 'Lane, Thomas E', 'Round, June L']",eLife.; 8:e47117,,,False
de562be49e01ca34319b504cbacad8d665d2d232,PMC,"Respiratory health, allergies, and the farm environment: design, methods and enrollment in the observational Wisconsin Infant Study Cohort (WISC): a research proposal",http://dx.doi.org/10.1186/s13104-019-4448-0,PMC6636141,31311588,CC BY,"Epidemiologic and cross-sectional studies suggest that early life farming and animal exposures are associated with major health benefits, influencing immune development and modifying the subsequent risk of allergic diseases, including asthma. The Wisconsin Infant Study Cohort (WISC) study was established in central Wisconsin to test the hypothesis that early life animal farm exposures are associated with distinct innate immune cell maturation trajectories, decreased allergen sensitization and reduced respiratory viral illness burden during the first 2 years of life. Beginning in 2013, a total of 240 families have been enrolled, 16,522 biospecimens have been collected, and 4098 questionnaires have been administered and entered into a secure database. Study endpoints include nasal respiratory virus identification and respiratory illness burden score, allergic sensitization, expression of allergic disease, and anti-viral immune response maturation and profiles. The WISC study prospective design, broad biospecimen collections, and unique US rural community will provide insights into the role of environmental exposures on early life immune maturation profiles associated with protection from allergic sensitization and significant respiratory viral disease burden. The WISC study findings will ultimately inform development of new strategies to promote resistance to severe respiratory viral illnesses and design primary prevention approaches for allergic diseases for all infants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-019-4448-0) contains supplementary material, which is available to authorized users.",2019 Jul 16,"['Seroogy, Christine M.', 'VanWormer, Jeffrey J.', 'Olson, Brent F.', 'Evans, Michael D.', 'Johnson, Tara', 'Cole, Deanna', 'Barnes, Kathrine L.', 'Koepel, Tamara Kronenwetter', 'Dresen, Amy', 'Meece, Jennifer', 'Gangnon, Ronald E.', 'Keifer, Matthew C.', 'Bendixsen, Casper G.', 'Gern, James E.', None]",BMC Res Notes,,,True
e0cbbb6421bb2fb309021936921aaadadfe74844,PMC,The emergence of porcine epidemic diarrhoea in Croatia: molecular characterization and serology,http://dx.doi.org/10.1186/s12917-019-2002-x,PMC6637520,31319854,CC BY,"BACKGROUND: Porcine epidemic diarrhoea (PED) is an emergent/re-emergent viral pig disease (caused by the virus belonging to the Coronaviridae family, in specific the Alphacoronavirus genus) of global importance. Clinical presentation is characterized with acute diarrhoea, vomiting and dehydration in pigs of all ages, with a possible high mortality in suckling piglets. The disease emerged in the USA in 2013 causing heavy losses, and re-emerged in Europe in 2014, but with milder consequences. RESULTS: In the spring 2016, PED-like symptoms were reported to be seen on an agricultural holding in Eastern Croatia; laboratory workup confirmed the Croatia’s first PED outbreak ever. Porcine epidemic diarrhoea virus (PEDV) strain responsible for the outbreak was of the S-INDEL genotype, much the same as other European PEDV strains. In 2017, a post-outbreak serology was carried out in three counties in Eastern Croatia, revealing seropositivity in pigs bred on four large industrial holdings (9.09%). The seroprevalence across PEDV-positive holdings was up to 82.8%. The latter holdings were unanimously managed by an enterprise that had never reported PED before. CONCLUSIONS: PED has emerged in Croatian pig population causing potentially considerable losses. The circulating strain was of the S-INDEL genotype. Serological workup proved PEDV spread to another four agricultural holdings, demonstrating the importance of not only external, but also internal biosecurity measures.",2019 Jul 18,"['Brnić, Dragan', 'Šimić, Ivana', 'Lojkić, Ivana', 'Krešić, Nina', 'Jungić, Andreja', 'Balić, Davor', 'Lolić, Marica', 'Knežević, Dražen', 'Hengl, Brigita']",BMC Vet Res,,,True
1f449c12090a1171943853457efa3d5272cfdb97,PMC,Bioinformatic Study of Transcriptome Changes in the Mice Lumbar Spinal Cord After the 30-Day Spaceflight and Subsequent 7-Day Readaptation on Earth: New Insights Into Molecular Mechanisms of the Hypogravity Motor Syndrome,http://dx.doi.org/10.3389/fphar.2019.00747,PMC6637859,31354476,CC BY,"The hypogravity motor syndrome (HMS) is one of the deleterious impacts of weightlessness on the human body in orbital space missions. There is a hypothesis that disorders of musculoskeletal system as part of HMS arise in consequence of changes in spinal motor neurons. The study was aimed at bioinformatic analysis of transcriptome changes in lumbar spinal cords of mice after a 30-day spaceflight aboard biosatellite Bion-M1 (space group, S) and subsequent 7-day readaptation to the Earth’s gravity (recovery group, R) when compared with control mice (C group) housed in simulated biosatellite conditions on the Earth. Gene ontology and human phenotype ontology databases were used to detect biological processes, molecular functions, cellular components, and human phenotypes associated with HMS. Our results suggest resemblance of molecular changes developing in space orbit and during the postflight recovery to terrestrial neuromuscular disorders. Remarkably, more prominent transcriptome changes were revealed in R vs. S and R vs. C comparisons that are possibly related to the 7-day recovery period in the Earth’s gravity condition. These data may assist with establishment of HMS pathogenesis and proposing effective preventive and therapeutic options.",2019 Jul 11,"['Kuznetsov, Maksim Sergeevich', 'Lisukov, Artur Nicolaevich', 'Rizvanov, Albert Anatolevich', 'Tyapkina, Oksana Victorovna', 'Gusev, Oleg Aleksandrovich', 'Rezvyakov, Pavel Nicolaevich', 'Kozlovskaya, Inessa Benedictovna', 'Tomilovskaya, Elena Sergeevna', 'Nikolskiy, Evgeny Evgenievich', 'Islamov, Rustem Robertovich']",Front Pharmacol,,,False
3911541ad43c2734d7e64deb63e319e085e54357,PMC,Bioinformatic Study of Transcriptome Changes in the Mice Lumbar Spinal Cord After the 30-Day Spaceflight and Subsequent 7-Day Readaptation on Earth: New Insights Into Molecular Mechanisms of the Hypogravity Motor Syndrome,http://dx.doi.org/10.3389/fphar.2019.00747,PMC6637859,31354476,CC BY,"The hypogravity motor syndrome (HMS) is one of the deleterious impacts of weightlessness on the human body in orbital space missions. There is a hypothesis that disorders of musculoskeletal system as part of HMS arise in consequence of changes in spinal motor neurons. The study was aimed at bioinformatic analysis of transcriptome changes in lumbar spinal cords of mice after a 30-day spaceflight aboard biosatellite Bion-M1 (space group, S) and subsequent 7-day readaptation to the Earth’s gravity (recovery group, R) when compared with control mice (C group) housed in simulated biosatellite conditions on the Earth. Gene ontology and human phenotype ontology databases were used to detect biological processes, molecular functions, cellular components, and human phenotypes associated with HMS. Our results suggest resemblance of molecular changes developing in space orbit and during the postflight recovery to terrestrial neuromuscular disorders. Remarkably, more prominent transcriptome changes were revealed in R vs. S and R vs. C comparisons that are possibly related to the 7-day recovery period in the Earth’s gravity condition. These data may assist with establishment of HMS pathogenesis and proposing effective preventive and therapeutic options.",2019 Jul 11,"['Kuznetsov, Maksim Sergeevich', 'Lisukov, Artur Nicolaevich', 'Rizvanov, Albert Anatolevich', 'Tyapkina, Oksana Victorovna', 'Gusev, Oleg Aleksandrovich', 'Rezvyakov, Pavel Nicolaevich', 'Kozlovskaya, Inessa Benedictovna', 'Tomilovskaya, Elena Sergeevna', 'Nikolskiy, Evgeny Evgenievich', 'Islamov, Rustem Robertovich']",Front Pharmacol,,,True
e2445316a3475f25e869fa303d9ec90f8739d40f,PMC,Identification of Ebola Virus Inhibitors Targeting GP2 Using Principles of Molecular Mimicry,http://dx.doi.org/10.1128/JVI.00676-19,PMC6639268,31092576,CC BY,"A key step in the Ebola virus (EBOV) replication cycle involves conformational changes in viral glycoprotein 2 (GP2) which facilitate host-viral membrane fusion and subsequent release of the viral genome. Ebola GP2 plays a critical role in virus entry and has similarities in mechanism and structure to the HIV gp41 protein for which inhibitors have been successfully developed. In this work, a putative binding pocket for the C-terminal heptad repeat in the N-terminal heptad repeat trimer was targeted for identification of small molecules that arrest EBOV-host membrane fusion. Two computational structure-based virtual screens of ∼1.7 M compounds were performed (DOCK program) against a GP2 five-helix bundle, resulting in 165 commercially available compounds purchased for experimental testing. Based on assessment of inhibitory activity, cytotoxicity, and target specificity, four promising candidates emerged with 50% inhibitory concentration values in the 3 to 26 μM range. Molecular dynamics simulations of the two most potent candidates in their DOCK-predicted binding poses indicate that the majority of favorable interactions involve seven highly conserved residues that can be used to guide further inhibitor development and refinement targeting EBOV. IMPORTANCE The most recent Ebola virus disease outbreak, from 2014 to 2016, resulted in approximately 28,000 individuals becoming infected, which led to over 12,000 causalities worldwide. The particularly high pathogenicity of the virus makes paramount the identification and development of promising lead compounds to serve as inhibitors of Ebola infection. To limit viral load, the virus-host membrane fusion event can be targeted through the inhibition of the class I fusion glycoprotein of Ebolavirus. In the current work, several promising small-molecule inhibitors that target the glycoprotein GP2 were identified through systematic application of structure-based computational and experimental drug design procedures.",2019 Jul 17,"['Singleton, Courtney D.', 'Humby, Monica S.', 'Yi, Hyun Ah', 'Rizzo, Robert C.', 'Jacobs, Amy']",J Virol,,,True
fcd795ee8b2f0c33dcc1a48d707162a3c9cac8ae,PMC,Avian Influenza A (H7N9) and related Internet search query data in China,http://dx.doi.org/10.1038/s41598-019-46898-y,PMC6639335,31320681,CC BY,"The use of Internet-based systems for infectious disease surveillance has been increasingly explored in recent years. However, few studies have used Internet search query or social media data to monitor spatial and temporal trends of avian influenza in China. This study investigated the potential of using search query and social media data in detecting and monitoring avian influenza A (H7N9) cases in humans in China. We collected weekly data on laboratory-confirmed H7N9 cases in humans, as well as H7N9-related Baidu Search Index (BSI) and Weibo Posting Index (WPI) data in China from 2013 to 2017, to explore the spatial and temporal trends of H7N9 cases and H7N9-related Internet search queries. Our findings showed a positive relationship of H7N9 cases with BSI and WPI search queries spatially and temporally. The outbreak threshold time and peak time of H7N9-related BSI and WPI searches preceded H7N9 cases in most years. Seasonal autoregressive integrated moving average (SARIMA) models with BSI (β = 0.008, p < 0.001) and WPI (β = 0.002, p = 0.036) were used to predict the number of H7N9 cases. Regression tree model analysis showed that the average H7N9 cases increased by over 2.4-fold (26.8/11) when BSI for H7N9 was >  = 11524. Both BSI and WPI data could be used as indicators to develop an early warning system for H7N9 outbreaks in the future.",2019 Jul 18,"['Chen, Ying', 'Zhang, Yuzhou', 'Xu, Zhiwei', 'Wang, Xuanzhuo', 'Lu, Jiahai', 'Hu, Wenbiao']",Sci Rep,,,False
4ade9fb8ea22a3cc6328dd972c7401c4cefc0a0c,PMC,Avian Influenza A (H7N9) and related Internet search query data in China,http://dx.doi.org/10.1038/s41598-019-46898-y,PMC6639335,31320681,CC BY,"The use of Internet-based systems for infectious disease surveillance has been increasingly explored in recent years. However, few studies have used Internet search query or social media data to monitor spatial and temporal trends of avian influenza in China. This study investigated the potential of using search query and social media data in detecting and monitoring avian influenza A (H7N9) cases in humans in China. We collected weekly data on laboratory-confirmed H7N9 cases in humans, as well as H7N9-related Baidu Search Index (BSI) and Weibo Posting Index (WPI) data in China from 2013 to 2017, to explore the spatial and temporal trends of H7N9 cases and H7N9-related Internet search queries. Our findings showed a positive relationship of H7N9 cases with BSI and WPI search queries spatially and temporally. The outbreak threshold time and peak time of H7N9-related BSI and WPI searches preceded H7N9 cases in most years. Seasonal autoregressive integrated moving average (SARIMA) models with BSI (β = 0.008, p < 0.001) and WPI (β = 0.002, p = 0.036) were used to predict the number of H7N9 cases. Regression tree model analysis showed that the average H7N9 cases increased by over 2.4-fold (26.8/11) when BSI for H7N9 was >  = 11524. Both BSI and WPI data could be used as indicators to develop an early warning system for H7N9 outbreaks in the future.",2019 Jul 18,"['Chen, Ying', 'Zhang, Yuzhou', 'Xu, Zhiwei', 'Wang, Xuanzhuo', 'Lu, Jiahai', 'Hu, Wenbiao']",Sci Rep,,,True
e47eb523372bb6d65a538c3678c78081dade7e9b,PMC,Lyon-IARC Polyomavirus DNA in Feces of Diarrheic Cats,http://dx.doi.org/10.1128/MRA.00550-19,PMC6639616,31320414,CC BY,"A viral metagenomic analysis of feces from an unexplained outbreak of feline diarrhea revealed the presence of Lyon-IARC polyomavirus (LIPyV) DNA. LIPyV, whose genome was originally sequenced from swabs of human skin, was fecally shed by three out of five diarrheic cats.",2019 Jul 18,"['Fahsbender, Elizabeth', 'Altan, Eda', 'Estrada, Marko', 'Seguin, M. Alexis', 'Young, Pauline', 'Leutenegger, Christian M.', 'Delwart, Eric']",Microbiol Resour Announc,,,True
6abb01ffd228ac3b5f92c02d9f7aa8d4df598fc4,PMC,Exosomes Derived From Septic Mouse Serum Modulate Immune Responses via Exosome-Associated Cytokines,http://dx.doi.org/10.3389/fimmu.2019.01560,PMC6640201,31354717,CC BY,"Sepsis is a life-threatening condition caused by an immune response triggered by infection, and highly elevated cytokine/chemokine levels in the blood play crucial roles in the progression of sepsis. Serum exosomes are nanovesicles that have multiple biological functions, playing roles in antigen presentation, intercellular signal communication, inflammatory response and immune surveillance. However, the biological functions and related molecular bases remain to be elucidated. In this study, we investigated the profiles of cytokines/chemokines harbored in the exosomes of septic mice and explored the mechanisms of immunomodulation on T cells treated with exosomes harvested from septic mice. Blood cytokines/chemokines existed in both the soluble form and in the insoluble exosomal form; the profiles of the cytokines/chemokines in these two forms displayed different dynamics in the blood of mice challenged with LPS. Exosomes from septic mice induced the differentiation of Th1/Th2 cells, which was blocked by specific antibodies targeting IL-12 and IL-4. In addition, these exosomes significantly augmented the proliferation and migration of T lymphocytes. Furthermore, preadministration of exosomes by intravenous injection restrained the inflammatory response, attenuated lung and liver tissue damage, and prolonged the survival of cecal ligation and puncture (CLP) mice. Our results indicate that exosomes enriched with cytokines/chemokines play critical roles in T cell differentiation, proliferation and chemotaxis during the sepsis process and have a protective effect on cecal ligation and puncture (CLP) mice. Thus, these findings not only strengthen our understanding of the role of sepsis via exosomes but also provide potential targets for therapeutic applications.",2019 Jul 12,"['Gao, Kun', 'Jin, Jingmiao', 'Huang, Chenyang', 'Li, Jianhang', 'Luo, Haihua', 'Li, Lei', 'Huang, Yukai', 'Jiang, Yong']",Front Immunol,,,False
d6c06b168e38dd8418fbc697bb3cd5abbc7cdaa6,PMC,Exosomes Derived From Septic Mouse Serum Modulate Immune Responses via Exosome-Associated Cytokines,http://dx.doi.org/10.3389/fimmu.2019.01560,PMC6640201,31354717,CC BY,"Sepsis is a life-threatening condition caused by an immune response triggered by infection, and highly elevated cytokine/chemokine levels in the blood play crucial roles in the progression of sepsis. Serum exosomes are nanovesicles that have multiple biological functions, playing roles in antigen presentation, intercellular signal communication, inflammatory response and immune surveillance. However, the biological functions and related molecular bases remain to be elucidated. In this study, we investigated the profiles of cytokines/chemokines harbored in the exosomes of septic mice and explored the mechanisms of immunomodulation on T cells treated with exosomes harvested from septic mice. Blood cytokines/chemokines existed in both the soluble form and in the insoluble exosomal form; the profiles of the cytokines/chemokines in these two forms displayed different dynamics in the blood of mice challenged with LPS. Exosomes from septic mice induced the differentiation of Th1/Th2 cells, which was blocked by specific antibodies targeting IL-12 and IL-4. In addition, these exosomes significantly augmented the proliferation and migration of T lymphocytes. Furthermore, preadministration of exosomes by intravenous injection restrained the inflammatory response, attenuated lung and liver tissue damage, and prolonged the survival of cecal ligation and puncture (CLP) mice. Our results indicate that exosomes enriched with cytokines/chemokines play critical roles in T cell differentiation, proliferation and chemotaxis during the sepsis process and have a protective effect on cecal ligation and puncture (CLP) mice. Thus, these findings not only strengthen our understanding of the role of sepsis via exosomes but also provide potential targets for therapeutic applications.",2019 Jul 12,"['Gao, Kun', 'Jin, Jingmiao', 'Huang, Chenyang', 'Li, Jianhang', 'Luo, Haihua', 'Li, Lei', 'Huang, Yukai', 'Jiang, Yong']",Front Immunol,,,True
147422b51b66a3e9c76f32fab4b4a004f67e8a16,PMC,Single-Domain Antibodies and Their Formatting to Combat Viral Infections,http://dx.doi.org/10.3390/antib8010001,PMC6640686,31544807,CC BY,"Since their discovery in the 1990s, single-domain antibodies (VHHs), also known as Nanobodies(®), have changed the landscape of affinity reagents. The outstanding solubility, stability, and specificity of VHHs, as well as their small size, ease of production and formatting flexibility favor VHHs over conventional antibody formats for many applications. The exceptional ease by which it is possible to fuse VHHs with different molecular modules has been particularly explored in the context of viral infections. In this review, we focus on VHH formats that have been developed to combat viruses including influenza viruses, human immunodeficiency virus-1 (HIV-1), and human respiratory syncytial virus (RSV). Such formats may significantly increase the affinity, half-life, breadth of protection of an antiviral VHH and reduce the risk of viral escape. In addition, VHHs can be equipped with effector functions, for example to guide components of the immune system with high precision to sites of viral infection.",2018 Dec 20,"['De Vlieger, Dorien', 'Ballegeer, Marlies', 'Rossey, Iebe', 'Schepens, Bert', 'Saelens, Xavier']",Antibodies (Basel),,,True
23dcdd1995567d482009f9eafaffc887da09701d,PMC,Experimental Data-Mining Analyses Reveal New Roles of Low-Intensity Ultrasound in Differentiating Cell Death Regulatome in Cancer and Non-cancer Cells via Potential Modulation of Chromatin Long-Range Interactions,http://dx.doi.org/10.3389/fonc.2019.00600,PMC6640725,31355136,CC BY,"Background: The mechanisms underlying low intensity ultrasound (LIUS) mediated suppression of inflammation and tumorigenesis remain poorly determined. Methods: We used microarray datasets from NCBI GEO Dataset databases and conducted a comprehensive data mining analyses, where we studied the gene expression of 299 cell death regulators that regulate 13 different cell death types (cell death regulatome) in cells treated with LIUS. Results: We made the following findings: (1) LIUS exerts a profound effect on the expression of cell death regulatome in cancer cells and non-cancer cells. Of note, LIUS has the tendency to downregulate the gene expression of cell death regulators in non-cancer cells. Most of the cell death regulator genes downregulated by LIUS in non-cancer cells are responsible for mediating inflammatory signaling pathways; (2) LIUS activates different cell death transcription factors in cancer and non-cancer cells. Transcription factors TP-53 and SRF- were induced by LIUS exposure in cancer cells and non-cancer cells, respectively; (3) As two well-accepted mechanisms of LIUS, mild hyperthermia and oscillatory shear stress induce changes in the expression of cell death regulators, therefore, may be responsible for inducing LIUS mediated changes in gene expression patterns of cell death regulators in cells; (4) LIUS exposure may change the redox status of the cells. LIUS may induce more of antioxidant effects in non-cancer cells compared to cancer cells; and (5) The genes modulated by LIUS in cancer cells have distinct chromatin long range interaction (CLRI) patterns to that of non-cancer cells. Conclusions: Our analysis suggests novel molecular mechanisms that may be utilized by LIUS to induce tumor suppression and inflammation inhibition. Our findings may lead to development of new treatment protocols for cancers and chronic inflammation.",2019 Jul 12,"['Wang, Jiwei', 'Lai, Bin', 'Nanayakkara, Gayani', 'Yang, Qian', 'Sun, Yu', 'Lu, Yifan', 'Shao, Ying', 'Yu, Daohai', 'Yang, William Y.', 'Cueto, Ramon', 'Fu, Hangfei', 'Zeng, Huihong', 'Shen, Wen', 'Wu, Susu', 'Zhang, Chunquan', 'Liu, Yanna', 'Choi, Eric T.', 'Wang, Hong', 'Yang, Xiaofeng']",Front Oncol,,,True
ae165f6805cbb0b5c688d4d5e5a89b6b7c16fae0,PMC,Evaluation of mouse enteroids as a model for Lawsonia intracellularis infection,http://dx.doi.org/10.1186/s13567-019-0672-9,PMC6642515,31324204,CC BY,"Lawsonia intracellularis, an obligate intracellular bacterium, is an important enteric pathogen in pig herds and horse farms worldwide. The hallmark feature of L. intracellularis infection is the proliferation of epithelial cells in intestinal crypts. A major limitation to the study of L. intracellularis infection is the lack of an in vitro model that reproduces the changes observed in proliferative enteropathy. Here we investigated the suitability of mouse enteroids as a model to study L. intracellularis infection. Mouse enteroids were microinjected with L. intracellularis, filter-sterilized L. intracellularis culture supernatant, or sterile cell culture media (DMEM). L. intracellularis antigen was detected in mouse enteroids by immunohistochemistry and was located mostly in the basal region of the epithelium. There was no differential growth of enteroids among treatment groups, and cellular proliferation was not increased in L. intracellularis-infected enteroids in relation to non-infected enteroids based on immunofluorescence staining. L. intracellularis infection did not induce changes in gene expression of Ki-67 (proliferation marker), Sox9 (marker for transit amplifying cells) and Muc2 (marker for goblet cells). These results indicate that although L. intracellularis antigen is detectable in mouse enteroids, indicating susceptibility to infection, mouse enteroids fail to replicate the cellular proliferation and gene expression changes observed in proliferative enteropathy. Nevertheless, we have successfully demonstrated that mouse enteroids can be used to model days-long intracellular pathogen infection, serving as potential models for the study of other pathogens of interest in veterinary medicine.",2019 Jul 19,"['Resende, Talita Pilar', 'Medida, Ramya Lekha', 'Guo, Yue', 'Vannucci, Fabio A.', 'Saqui-Salces, Milena', 'Gebhart, Connie']",Vet Res,,,True
b6ad9d6a39c2a67b36e8d058d2e57ba08423afc3,PMC,Development of oligonucleotide microarray for accurate and simultaneous detection of avian respiratory viral diseases,http://dx.doi.org/10.1186/s12917-019-1985-7,PMC6642548,31324180,CC BY,"BACKGROUND: Avian influenza virus (AIV), infectious bronchitis virus (IBV), and Newcastle disease virus (NDV) are important avian pathogens that can cause enormous economic loss on the poultry industry. Different respiratory etiological agents may induce similar clinical signs that make differential diagnosis difficult. Importantly, AIV brings about severe threat to human public health. Therefore, a novel method that can distinguish these viruses quickly and simultaneously is urgently needed. RESULTS: In this study, an oligonucleotide microarray system was developed. AIV, including H5, H7, and H9 subtypes; NDV; and IBV were simultaneously detected and differentiated on a microarray. Three probes specific for AIV, NDV, and IBV, as well as three other probes for differentiating H5, H7, and H9 of AIV, were first designed and jet-printed to predetermined locations of initiator-integrated poly(dimethylsiloxane) for the synchronous detection of the six pathogens. The marked multiplex reverse transcription polymerase chain reaction (PCR) products were hybridized with the specific probes, and the results of hybridization were read directly with the naked eyes. No cross-reaction was observed with 10 other subtypes of AIV and infectious bursal disease virus, indicating that the oligonucleotide microarray assay was highly specific. The sensitivity of the method was at least 100 times higher than that of the conventional PCR, and the detection limit of NDV, AIV, H5, H7, and H9 can reach 0.1 EID(50) (50% egg infective dose), except that of IBV, which was 1 EID(50) per reaction. In the validation of 93 field samples, AIV, IBV, and NDV were detected in 53 (56.99%) samples by oligonucleotide microarray and virus isolation and in 50 (53.76%) samples by conventional PCR. CONCLUSIONS: We have successfully developed an approach to differentiate AIV, NDV, IBV, H5, H7, and H9 subtypes of AIV using oligonucleotide microarray. The microarray is an accurate, high-throughput, and relatively simple method for the rapid detection of avian respiratory viral diseases. It can be used for the epidemiological surveillance and diagnosis of AIV, IBV, and NDV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-019-1985-7) contains supplementary material, which is available to authorized users.",2019 Jul 19,"['Xiao, Qian', 'Yan, Liping', 'Yao, Lu', 'Lei, Jing', 'Bi, Zhenwei', 'Hu, Jianhua', 'Chen, Yuqing', 'Fang, An', 'Li, Hui', 'Li, Yuan', 'Yan, Yan', 'Zhou, Jiyong']",BMC Vet Res,,,True
67a72161f9ca2ec9aa5649980667e7fef2125539,PMC,Influenza virus-related critical illness: pathophysiology and epidemiology,http://dx.doi.org/10.1186/s13054-019-2539-x,PMC6642581,31324202,CC BY,"Influenza virus affects the respiratory tract by direct viral infection or by damage from the immune system response. In humans, the respiratory epithelium is the only site where the hemagglutinin (HA) molecule is effectively cleaved, generating infectious virus particles. Virus transmission occurs through a susceptible individual’s contact with aerosols or respiratory fomites from an infected individual. The inability of the lung to perform its primary function of gas exchange can result from multiple mechanisms, including obstruction of the airways, loss of alveolar structure, loss of lung epithelial integrity from direct epithelial cell killing, and degradation of the critical extracellular matrix. Approximately 30–40% of hospitalized patients with laboratory-confirmed influenza are diagnosed with acute pneumonia. These patients who develop pneumonia are more likely to be < 5 years old, > 65 years old, Caucasian, and nursing home residents; have chronic lung or heart disease and history of smoking, and are immunocompromised. Influenza can primarily cause severe pneumonia, but it can also present in conjunction with or be followed by a secondary bacterial infection, most commonly by Staphylococcus aureus and Streptococcus pneumoniae. Influenza is associated with a high predisposition to bacterial sepsis and ARDS. Viral infections presenting concurrently with bacterial pneumonia are now known to occur with a frequency of 30–50% in both adult and pediatric populations. The H3N2 subtype has been associated with unprecedented high levels of intensive care unit (ICU) admission. Influenza A is the predominant viral etiology of acute respiratory distress syndrome (ARDS) in adults. Risk factors independently associated with ARDS are age between 36 and 55 years old, pregnancy, and obesity, while protective factors are female sex, influenza vaccination, and infections with Influenza A (H3N2) or Influenza B viruses. In the ICU, particularly during the winter season, influenza should be suspected not only in patients with typical symptoms and epidemiology, but also in patients with severe pneumonia, ARDS, sepsis with or without bacterial co-infection, as well as in patients with encephalitis, myocarditis, and rhabdomyolysis.",2019 Jul 19,"['Kalil, Andre C.', 'Thomas, Paul G.']",Crit Care,,,True
f32dc6c0ebf9a1623dc3b3b3eb15cfbaf12755d4,PMC,First detection and genetic characterization of canine Kobuvirus in domestic dogs in Thailand,http://dx.doi.org/10.1186/s12917-019-1994-6,PMC6642606,31324182,CC BY,"BACKGROUND: Canine Kobuvirus (CaKoV) has been detected both in healthy and diarrheic dogs and in asymptomatic wild carnivores. In this study, we conducted a survey of CaKoV at small animal hospitals in Bangkok and vicinity of Thailand during September 2016 to September 2018. RESULTS: Three hundred and seven rectal swab samples were collected from healthy dogs (n = 55) and dogs with gastroenteritis symptoms (n = 252). Of 307 swab samples tested by using one-step RT-PCR specific to 3D gene, we found CaKoV positivity at 17.59% (54/307). CaKoVs could be detected in both sick (19.44%) and healthy (9.09%) animals. In relation to age group, CaKoV could be frequently detected in younger dogs (25.45%). Our result showed no seasonal pattern of CaKoV infection in domestic dogs. In this study, we characterized CaKoVs by whole genome sequencing (n = 4) or 3D and VP1 gene sequencing (n = 8). Genetic and phylogenetic analyses showed that whole genomes of Thai CaKoVs were closely related to Chinese CaKoVs with highest 99.5% amino acid identity suggesting possible origin of CaKoVs in Thailand. CONCLUSIONS: In conclusion, this study was the first to report the detection and genetic characteristics of CaKoVs in domestic dogs in Thailand. CaKoVs could be detected in both sick and healthy dogs. The virus is frequently detected in younger dogs. Thai CaKoVs were genetically closely related and grouped with Chinese CaKoVs. Our result raises the concerns to vet practitioners that diarrhea in dogs due to canine Kobuvirus infection should not be ignored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-019-1994-6) contains supplementary material, which is available to authorized users.",2019 Jul 19,"['Charoenkul, Kamonpan', 'Janetanakit, Taveesak', 'Chaiyawong, Supassama', 'Bunpapong, Napawan', 'Boonyapisitsopa, Supanat', 'Tangwangvivat, Ratanaporn', 'Amonsin, Alongkorn']",BMC Vet Res,,,True
b97ac8d30646b2d3cc9ab2f7447534e9ecefbeee,PMC,Differential transcriptional profiles identify microglial- and macrophage-specific gene markers expressed during virus-induced neuroinflammation,http://dx.doi.org/10.1186/s12974-019-1545-x,PMC6642742,31325960,CC BY,"BACKGROUND: In the healthy central nervous system (CNS), microglia are found in a homeostatic state and peripheral macrophages are absent from the brain. Microglia play key roles in maintaining CNS homeostasis and acting as first responders to infection and inflammation, and peripheral macrophages infiltrate the CNS during neuroinflammation. Due to their distinct origins and functions, discrimination between these cell populations is essential to the comprehension of neuroinflammatory disorders. Studies comparing the gene profiles of microglia and peripheral macrophages, or macrophages in vitro-derived from bone marrow, under non-infectious conditions of the CNS, have revealed valuable microglial-specific genes. However, studies comparing gene profiles between CNS-infiltrating macrophages and microglia, when both are isolated from the CNS during viral-induced neuroinflammation, are lacking. METHODS: We isolated, via flow cytometry, microglia and infiltrating macrophages from the brains of Theiler’s murine encephalomyelitis virus-infected C57BL/6 J mice and used RNA-Seq, followed by validation with qPCR, to examine the differential transcriptional profiles of these cells. We utilized primary literature defining subcellular localization to determine whether or not particular proteins extracted from the transcriptional profiles were expressed at the cell surface. The surface expression and cellular specificity of triggering receptor expressed on myeloid cells 1 (TREM-1) protein were examined via flow cytometry. We also examined the immune response gene profile within the transcriptional profiles of these isolated microglia and infiltrating macrophages. RESULTS: We have identified and validated new microglial- and macrophage-specific genes, encoding cell surface proteins, expressed at the peak of neuroinflammation. TREM-1 protein was confirmed to be expressed by infiltrating macrophages, not microglia, at the peak of neuroinflammation. We also identified both unique and redundant immune functions, through examination of the immune response gene profiles, of microglia and infiltrating macrophages during neurotropic viral infection. CONCLUSIONS: The differential expression of cell surface-specific genes during neuroinflammation can potentially be used to discriminate between microglia and macrophages as well as provide a resource that can be further utilized to target and manipulate specific cell responses during neuroinflammation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-019-1545-x) contains supplementary material, which is available to authorized users.",2019 Jul 20,"['DePaula-Silva, Ana Beatriz', 'Gorbea, Carlos', 'Doty, Daniel J.', 'Libbey, Jane E.', 'Sanchez, John Michael S.', 'Hanak, Tyler J.', 'Cazalla, Demián', 'Fujinami, Robert S.']",J Neuroinflammation,,,True
b4d499844440e3aacd1644715092e8d170e39517,PMC,Epidemiology and prevention of influenza in children in Argentina and Brazil,http://dx.doi.org/10.26633/RPSP.2017.76,PMC6645205,28628185,CC BY,"A group of influenza experts from Argentina and Brazil got together to discuss the burden of influenza in children, review current vaccine coverage rates in both countries, analyze vaccine effectiveness, and discuss strategies to improve prevention. Active surveillance of respiratory viruses is carried out nationwide in both countries. Years 2014 and 2015 were mild influenza seasons; influenza virus type A/H3N2 prevailed, whereas type B represented less than 30% of isolates. Trivalent inactivated influenza vaccine is included in National Immunization Programs for 1) children 6 months to 2 years old in Argentina; 2) children 6 months to 5 years old in Brazil; and 3) all high-risk individuals. Coverage rates in both countries were about 80% (albeit lower for the second dose). Experts from both countries proposed the following strategies to improve prevention: 1) increase surveillance; 2) assess effectiveness and long-term safety of influenza vaccines; 3) reinforce vaccination programs in order to increase coverage rates; and 4)consider introducing more effective vaccines, such as adjuvanted trivalent vaccines. In Argentina, estimating casefatality rates was also recommended. Other proposed actions included enhancing education of health professionals and the lay community, and better use of communication resources to raise awareness of the burden of influenza and promote vaccine uptake.",2017 Apr 28,"Argentinean Influenza Brazilian Working Group Vaccine,",Rev Panam Salud Publica,,,True
7aaffdb8cf80ab9dd167a26a44abfa21d30d2af5,PMC,Superior immune responses induced by intranasal immunization with recombinant adenovirus-based vaccine expressing full-length Spike protein of Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1371/journal.pone.0220196,PMC6645677,31329652,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes an acute and severe lower respiratory illness as well as vomiting, diarrhea, and renal failure. Because no licensed MERS-CoV vaccines are currently available, preventive and therapeutic measures are urgently needed. The surface spike (S) glycoprotein of MERS-CoV, which binds to the cellular receptor dipeptidyl peptidase 4 (DPP4), is considered as a major target for MERS-CoV vaccine development. Here, we designed recombinant replication-deficient adenovirus-based vaccines expressing the N-terminal domain (rAd/NTD) and receptor-binding domain (rAd/RBD) of the MERS-CoV S1 subunit and full-length Spike protein (rAd/Spike). We found that immunization with candidate vaccines via intranasal route induced S1-specific IgG antibodies and neutralizing antibodies against MERS spike pseudotyped virus. Especially, rAd/Spike induced the highest neutralizing antibody titer and the strongest cytokine-induced T cell responses among the three candidate vaccines. To compare the immune responses induced by different administration routes, rAd/Spike was administered via intranasal, sublingual, or intramuscular route. All these administration routes exhibited neutralizing effects in the serum. MERS-CoV-specific neutralizing IgA antibodies in the bronchoalveolar lavage fluid were only induced by intranasal and sublingual administration but not by intramuscular administration. Intranasal administration with rAd/Spike also created resident memory CD8 T cells in the airway and lung parenchyma. Taken together, our results showed that both the humoral and cellular immune responses are highly induced by rAd/Spike administration, suggesting that rAd/Spike may confer protection against MERS-CoV infection.",2019 Jul 22,"['Kim, Myung Hee', 'Kim, Hyun Jik', 'Chang, Jun']",PLoS One,,,True
735dca3ec505ecf1a2e01d913c945a7d18f3efcf,PMC,Hepatitis E in southern Vietnam: Seroepidemiology in humans and molecular epidemiology in pigs,http://dx.doi.org/10.1111/zph.12364,PMC6645987,28598034,CC BY,"Viral pathogens account for a significant proportion of the burden of emerging infectious diseases in humans. The Wellcome Trust-Vietnamese Initiative on Zoonotic Infections (WT-VIZIONS) is aiming to understand the circulation of viral zoonotic pathogens in animals that pose a potential risk to human health. Evidence suggests that human exposure and infections with hepatitis E virus (HEV) genotypes (GT) 3 and 4 results from zoonotic transmission. Hypothesising that HEV GT3 and GT4 are circulating in the Vietnamese pig population and can be transmitted to humans, we aimed to estimate the seroprevalence of HEV exposure in a population of farmers and the general population. We additionally performed sequence analysis of HEV in pig populations in the same region to address knowledge gaps regarding HEV circulation and to evaluate if pigs were a potential source of HEV exposure. We found a high prevalence of HEV GT3 viral RNA in pigs (19.1% in faecal samples and 8.2% in rectal swabs) and a high HEV seroprevalence in pig farmers (16.0%) and a hospital-attending population (31.7%) in southern Vietnam. The hospital population was recruited as a general-population proxy even though this particular population subgroup may introduce bias. The detection of HEV RNA in pigs indicates that HEV may be a zoonotic disease risk in this location, although a larger sample size is required to infer an association between HEV positivity in pigs and seroprevalence in humans.",2018 Feb 1,"['Berto, A.', 'Pham, H. A.', 'Thao, T. T. N.', 'Vy, N. H. T.', 'Caddy, S. L.', 'Hiraide, R.', 'Tue, N. T.', 'Goodfellow, I.', 'Carrique-Mas, J. J.', 'Thwaites, G. E.', 'Baker, S.', 'Boni, M. F.']",Zoonoses Public Health,,,True
fe6515a4d40bf3c4c53be769971d38fada210810,PMC,Seasonality of respiratory viruses and bacterial pathogens,http://dx.doi.org/10.1186/s13756-019-0574-7,PMC6647268,31367346,CC BY,"BACKGROUND: Seasonal variation has been observed for various bacterial and viral infections. We aimed to further study seasonality of respiratory viruses and bacterial pathogens in relation to antibiotic use, as well as meteorological parameters. METHODS: An ecologic study of antibiotic exposure, meteorological parameters, detection of respiratory viruses  and clinical isolates of Clostridioides difficile, Methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, and Escherichia coli and Klebsiella pneumoniae (grouped together as gram-negative bacteria; GNB) in Rhode Island from 2012 to 2016. RESULTS: Peak detection of C. difficile occurred 3 months after the peak in antibiotic prescriptions filled (OR = 1.24, 95% CI, 1.07–1.43; P = 0.006). Peak MRSA detection was noted 7 months after the peak in antibiotic prescriptions filled (OR = 1.69, 95% CI, 1.21–2.35; P = 0.003) and 10 months after the peak in respiratory virus detection (OR = 1.04, 95% CI, 1.01–1.06; P = 0.003). Peak GNB detection was noted 2 months after the peak mean monthly ambient temperature (OR = 1.69, 95% C.I., 1.20–2.39; P = 0.004). Peak detection of S. pneumoniae was noted at the same time as the peak in detection of respiratory viruses (OR = 1.01, 95% C.I., 1.00–1.01; P = 0.015). CONCLUSIONS: We identified distinct seasonal variation in detection of respiratory viruses and bacterial pathogens. C. difficile seasonality may, in part, be related to antibiotic prescriptions filled; GNB seasonality may be related to ambient temperature and S. pneumoniae may be related to concurrent respiratory viral infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13756-019-0574-7) contains supplementary material, which is available to authorized users.",2019 Jul 22,"['Choe, Young June', 'Smit, Michael A.', 'Mermel, Leonard A.']",Antimicrob Resist Infect Control,,,True
b453be7df859d451667f709fbb0c843cf0b9f25c,PMC,Biguanide is a modifiable pharmacophore for recruitment of endogenous Zn(2+) to inhibit cysteinyl cathepsins: review and implications,http://dx.doi.org/10.1007/s10534-019-00197-1,PMC6647370,31044334,CC BY,"ABSTRACT: Excessive activities of cysteinyl cathepsins (CysCts) contribute to the progress of many diseases; however, therapeutic inhibition has been problematic. Zn(2+) is a natural inhibitor of proteases with CysHis dyads or CysHis(Xaa) triads. Biguanide forms bidentate metal complexes through the two imino nitrogens. Here, it is discussed that phenformin (phenylethyl biguanide) is a model for recruitment of endogenous Zn(2+) to inhibit CysHis/CysHis(X) peptidolysis. Phenformin is a Zn(2+)-interactive, anti-proteolytic agent in bioassay of living tissue. Benzoyl-l-arginine amide (BAA) is a classical substrate of papain-like proteases; the amide bond is scissile. In this review, the structures of BAA and the phenformin-Zn(2+) complex were compared in silico. Their chemistry and dimensions are discussed in light of the active sites of papain-like proteases. The phenyl moieties of both structures bind to the “S2” substrate-binding site that is typical of many proteases. When the phenyl moiety of BAA binds to S2, then the scissile amide bond is directed to the position of the thiolate-imidazolium ion pair, and is then hydrolyzed. However, when the phenyl moiety of phenformin binds to S2, then the coordinated Zn(2+) is directed to the identical position; and catalysis is inhibited. Phenformin stabilizes a “Zn(2+) sandwich” between the drug and protease active site. Hundreds of biguanide derivatives have been synthesized at the 1 and 5 nitrogen positions; many more are conceivable. Various substituent moieties can register with various arrays of substrate-binding sites so as to align coordinated Zn(2+) with catalytic partners of diverse proteases. Biguanide is identified here as a modifiable pharmacophore for synthesis of therapeutic CysCt inhibitors with a wide range of potencies and specificities. GRAPHICAL ABSTRACT: Phenformin-Zn(2+) Complex [Image: see text]",2019 May 1,"Lockwood, Thomas D.",Biometals,,,True
cf6aa226d19188bcb5215d3d1cced4773a82b6f8,PMC,Identification of hepadnavirus in the sera of cats,http://dx.doi.org/10.1038/s41598-019-47175-8,PMC6650429,31337847,CC BY,"Hepadnaviruses infect several animal species. The prototype species, human hepatitis B virus (HBV), increases the risk of liver diseases and may cause cirrhosis and hepatocellular carcinoma. Recently a novel hepadnavirus, similar to HBV, has been identified through transcriptomics studies in a domestic cat with large cell lymphoma in Australia. Herewith, a collection of 390 feline serum samples was screened for hepadnavirus. Overall, the virus was identified in 10.8% of the sera with a significantly higher prevalence (17.8%) in the sera of animals with a clinical suspect of infectious disease. Upon genome sequencing, the virus was closely related (97.0% nt identity) to the prototype Australian feline virus Sydney 2016. The mean and median values of hepadnavirus in the feline sera were 1.3 × 10(6) and 2.1 × 10(4) genome copies per mL (range 3.3 × 10(0)–2.5 × 10(7) genome copies per mL). For a subset of hepadnavirus-positive samples, information on the hemato-chemical parameters was available and in 10/20 animals a profile suggestive of liver damage was present. Also, in 7/10 animals with suspected hepatic disease, virus load was >10(4) genome copies per mL, i.e. above the threshold considered at risk of active hepatitis and liver damage for HBV.",2019 Jul 23,"['Lanave, Gianvito', 'Capozza, Paolo', 'Diakoudi, Georgia', 'Catella, Cristiana', 'Catucci, Leonardo', 'Ghergo, Paola', 'Stasi, Fabio', 'Barrs, Vanessa', 'Beatty, Julia', 'Decaro, Nicola', 'Buonavoglia, Canio', 'Martella, Vito', 'Camero, Michele']",Sci Rep,,,True
061eb24a1462aba7b53e6c099fe5d4bd046dd56a,PMC,G-Quadruplex-Based Fluorescent Turn-On Ligands and Aptamers: From Development to Applications,http://dx.doi.org/10.3390/molecules24132416,PMC6650947,31262059,CC BY,"Guanine (G)-quadruplexes (G4s) are unique nucleic acid structures that are formed by stacked G-tetrads in G-rich DNA or RNA sequences. G4s have been reported to play significant roles in various cellular events in both macro- and micro-organisms. The identification and characterization of G4s can help to understand their different biological roles and potential applications in diagnosis and therapy. In addition to biophysical and biochemical methods to interrogate G4 formation, G4 fluorescent turn-on ligands can be used to target and visualize G4 formation both in vitro and in cells. Here, we review several representative classes of G4 fluorescent turn-on ligands in terms of their interaction mechanism and application perspectives. Interestingly, G4 structures are commonly identified in DNA and RNA aptamers against targets that include proteins and small molecules, which can be utilized as G4 tools for diverse applications. We therefore also summarize the recent development of G4-containing aptamers and highlight their applications in biosensing, bioimaging, and therapy. Moreover, we discuss the current challenges and future perspectives of G4 fluorescent turn-on ligands and G4-containing aptamers.",2019 Jun 30,"['Umar, Mubarak I.', 'Ji, Danyang', 'Chan, Chun-Yin', 'Kwok, Chun Kit']",Molecules,,,True
162d42b98a0abdf3d7ee609fe464918e457f55fd,PMC,Measles infection causing Bacillus Calmette-Guérin reactivation: a case report,http://dx.doi.org/10.1186/s12887-019-1635-z,PMC6652017,31340782,CC BY,"BACKGROUND: Reactivation of the Bacillus Calmette-Guérin (BCG), manifesting as erythema, induration, ulceration or crust formation at a previous BCG inoculation site, is a common and highly specific feature of Kawasaki disease (KD). We report the unusual finding of BCG reactivation in an infant with laboratory-confirmed measles. CASE PRESENTATION: A previously healthy 7-month old infant presented initially with fever, cough and coryza, and subsequently developed Koplik’s spots followed by a typical morbilliform skin rash. There was significant contact history with a household relative who had recently been diagnosed with measles. On examination, a 2.5 cm area of erythema and induration was seen at the previous BCG inoculation site, in addition to the widespread maculopapular rash. No other clinical features of KD were present. Measles virus was isolated from the throat swab and measles antibodies (IgM) were present in the serum. The patient recovered completely with oral vitamin A and supportive therapy, and had normal echocardiography examination on follow up. CONCLUSIONS: This case report highlights the rare finding of BCG reactivation in a child with confirmed measles infection, and suggests that this clinical manifestation may occasionally occur in children with infections or conditions other than KD.",2019 Jul 24,"['Muthuvelu, Sobana', 'Lim, Kev Shiau-Chong', 'Huang, Ling-Yin', 'Chin, Shi-Tying', 'Mohan, Anand']",BMC Pediatr,,,True
401ebad7d8d7416f0bf26c8192eb57bfb61f378b,PMC,Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5,http://dx.doi.org/10.3389/fimmu.2019.01586,PMC6652118,31379819,CC BY,"RIG-I (Retinoic acid-inducible gene I) and MDA5 (Melanoma Differentiation-Associated protein 5), collectively known as the RIG-I-like receptors (RLRs), are key protein sensors of the pathogen-associated molecular patterns (PAMPs) in the form of viral double-stranded RNA (dsRNA) motifs to induce expression of type 1 interferons (IFN1) (IFNα and IFNβ) and other pro-inflammatory cytokines during the early stage of viral infection. While RIG-I and MDA5 share many genetic, structural and functional similarities, there is increasing evidence that they can have significantly different strategies to recognize different pathogens, PAMPs, and in different host species. This review article discusses the similarities and differences between RIG-I and MDA5 from multiple perspectives, including their structures, evolution and functional relationships with other cellular proteins, their differential mechanisms of distinguishing between host and viral dsRNAs and interactions with host and viral protein factors, and their immunogenic signaling. A comprehensive comparative analysis can help inform future studies of RIG-I and MDA5 in order to fully understand their functions in order to optimize potential therapeutic approaches targeting them.",2019 Jul 17,"['Brisse, Morgan', 'Ly, Hinh']",Front Immunol,,,True
3a676f4ebe85b17d5aedd055c0af967760e13e64,PMC,Deciphering Fc-mediated Antiviral Antibody Functions in Animal Models,http://dx.doi.org/10.3389/fimmu.2019.01602,PMC6652135,31379822,CC BY,"Longstanding discordances and enigmas persist as to the specificities and other properties of antibodies (Abs) most effective in preventing or limiting many viral infections in mammals; in turn, failure to decipher key complexities has added to headwinds for both Ab-based therapeutic approaches and rational vaccine design. More recently, experimental approaches have emerged—and continue to emerge—for discerning the functional role of Ab structure, especially the Fc portion of antibody, in combating viral infections in vivo. A wide range of in vitro measures of antibody activity, from neutralization to antibody-dependent cell mediated cytotoxicity (ADCC)—each of these terms representing only an operational notion defined by the particulars of a given assay—are poised for assignment of both relevance and reliability in forecasting outcomes of infection. Of the several emergent technical opportunities for clarity, attention here is drawn to three realms: the increasing array of known modifications that can be engineered into Abs to affect their in vivo activities; the improvement of murine models involving knockouts and knock-ins of host genes including Fc receptors; and the development of additional virological design tools to differentiate Abs that act primarily by inhibiting viral entry from antibodies that mainly target viral antigens (Ags) on cell surfaces. To illustrate some of the opportunities with either zoonotic (emerging, spillover) or ancient human-adapted viruses, we draw examples from a wide range of viruses that affect humans.",2019 Jul 17,"['Schmaljohn, Alan L.', 'Orlandi, Chiara', 'Lewis, George K.']",Front Immunol,,,True
88c599b1de8a17cd519f9f72aaaea28392f697f0,PMC,The Capsid Protein VP1 of Coxsackievirus B Induces Cell Cycle Arrest by Up-Regulating Heat Shock Protein 70,http://dx.doi.org/10.3389/fmicb.2019.01633,PMC6653663,31379784,CC BY,"Manipulating cell cycle is one of the common strategies used by viruses to generate favorable cellular environment to facilitate viral replication. Coxsackievirus B (CVB) is one of the major viral pathogens of human myocarditis and cardiomyopathy. Because of its small genome, CVB depends on cellular machineries for productive replication. However, how the structural and non-structural components of CVB would manipulate cell cycle is not clearly understood. In this study, we demonstrated that the capsid protein VP1 of CVB type 3 (CVB3) induced cell cycle arrest at G1 phase. G1 arrest was the result of the decrease level of cyclin E and the accumulation of p27(Kip1). Study on the gene expression profile of the cells expressing VP1 showed that the expression of both heat shock protein 70-1 (Hsp70-1) and Hsp70-2 was significantly up-regulated. Knockdown of Hsp70 resulted in the increased level of cyclin E and the reduction of p27(Kip1). We further demonstrated that the phosphorylation of the heat shock factor 1, which directly promotes the expression of Hsp70, was also increased in the cell expressing VP1. Moreover, we show that CVB3 infection also induced G1 arrest, likely due to dysregulating Hsp70, cyclin E, and p27, while knockdown of Hsp70 dramatically inhibited viral replication. Cell cycle arrest at G1 phase facilitated CVB3 infection, since viral replication in the cells synchronized at G1 phase dramatically increased. Taken together, this study demonstrates that the VP1 of CVB3 induces cell cycle arrest at G1 phase through up-regulating Hsp70. Our findings suggest that the capsid protein VP1 of CVB is capable of manipulating cellular activities during viral infection.",2019 Jul 17,"['Wang, Yao', 'Zhao, Shuoxuan', 'Chen, Yang', 'Wang, Tianying', 'Dong, Chaorun', 'Wo, Xiaoman', 'Zhang, Jian', 'Dong, Yanyan', 'Xu, Weizhen', 'Feng, Xiaofeng', 'Qu, Cong', 'Wang, Yan', 'Zhong, Zhaohua', 'Zhao, Wenran']",Front Microbiol,,,True
1986b0795d747225509369644cec05194d09a43c,PMC,A cell-based assay for CD63-containing extracellular vesicles,http://dx.doi.org/10.1371/journal.pone.0220007,PMC6655660,31339911,CC BY,"Extracellular vesicles (EVs) are thought to be important in cell-cell communication and have elicited extraordinary interest as potential biomarkers of disease. However, quantitative methods to enable elucidation of mechanisms underlying release are few. Here, we describe a cell-based assay for monitoring EV release using the EV-enriched tetraspanin CD63 fused to the small, ATP-independent reporter enzyme, Nanoluciferase. Release of CD63-containing EVs from stably expressing cell lines was monitored by comparing luciferase activity in culture media to that remaining in cells. HEK293, U2OS, U87 and SKMel28 cells released 0.3%-0.6% of total cellular CD63 in the form of EVs over 5 hrs, varying by cell line. To identify cellular machinery important for secretion of CD63-containing EVs, we performed a screen of biologically active chemicals in HEK293 cells. While a majority of compounds did not significantly affect EV release, treating cells with the plecomacrolides bafilomycin or concanamycin, known to inhibit the V-ATPase, dramatically increased EV release. Interestingly, alkalization of the endosomal lumen using weak bases had no effect, suggesting a pH-independent enhancement of EV release by V-ATPase inhibitors. The ability to quantify EVs in small samples will enable future detailed studies of release kinetics as well as further chemical and genetic screening to define pathways involved in EV secretion.",2019 Jul 24,"['Cashikar, Anil G.', 'Hanson, Phyllis I.']",PLoS One,,,True
c70af129da65e5791d82e0584950d8ce129baf0c,PMC,A cell-based assay for CD63-containing extracellular vesicles,http://dx.doi.org/10.1371/journal.pone.0220007,PMC6655660,31339911,CC BY,"Extracellular vesicles (EVs) are thought to be important in cell-cell communication and have elicited extraordinary interest as potential biomarkers of disease. However, quantitative methods to enable elucidation of mechanisms underlying release are few. Here, we describe a cell-based assay for monitoring EV release using the EV-enriched tetraspanin CD63 fused to the small, ATP-independent reporter enzyme, Nanoluciferase. Release of CD63-containing EVs from stably expressing cell lines was monitored by comparing luciferase activity in culture media to that remaining in cells. HEK293, U2OS, U87 and SKMel28 cells released 0.3%-0.6% of total cellular CD63 in the form of EVs over 5 hrs, varying by cell line. To identify cellular machinery important for secretion of CD63-containing EVs, we performed a screen of biologically active chemicals in HEK293 cells. While a majority of compounds did not significantly affect EV release, treating cells with the plecomacrolides bafilomycin or concanamycin, known to inhibit the V-ATPase, dramatically increased EV release. Interestingly, alkalization of the endosomal lumen using weak bases had no effect, suggesting a pH-independent enhancement of EV release by V-ATPase inhibitors. The ability to quantify EVs in small samples will enable future detailed studies of release kinetics as well as further chemical and genetic screening to define pathways involved in EV secretion.",2019 Jul 24,"['Cashikar, Anil G.', 'Hanson, Phyllis I.']",PLoS One,,,False
4f9e5f57915482696a9942c05feb6086bfa4d3f3,PMC,A cell-based assay for CD63-containing extracellular vesicles,http://dx.doi.org/10.1371/journal.pone.0220007,PMC6655660,31339911,CC BY,"Extracellular vesicles (EVs) are thought to be important in cell-cell communication and have elicited extraordinary interest as potential biomarkers of disease. However, quantitative methods to enable elucidation of mechanisms underlying release are few. Here, we describe a cell-based assay for monitoring EV release using the EV-enriched tetraspanin CD63 fused to the small, ATP-independent reporter enzyme, Nanoluciferase. Release of CD63-containing EVs from stably expressing cell lines was monitored by comparing luciferase activity in culture media to that remaining in cells. HEK293, U2OS, U87 and SKMel28 cells released 0.3%-0.6% of total cellular CD63 in the form of EVs over 5 hrs, varying by cell line. To identify cellular machinery important for secretion of CD63-containing EVs, we performed a screen of biologically active chemicals in HEK293 cells. While a majority of compounds did not significantly affect EV release, treating cells with the plecomacrolides bafilomycin or concanamycin, known to inhibit the V-ATPase, dramatically increased EV release. Interestingly, alkalization of the endosomal lumen using weak bases had no effect, suggesting a pH-independent enhancement of EV release by V-ATPase inhibitors. The ability to quantify EVs in small samples will enable future detailed studies of release kinetics as well as further chemical and genetic screening to define pathways involved in EV secretion.",2019 Jul 24,"['Cashikar, Anil G.', 'Hanson, Phyllis I.']",PLoS One,,,False
39ffcf08a8418996ba75eab6b42813093cd6f8fa,PMC,A cell-based assay for CD63-containing extracellular vesicles,http://dx.doi.org/10.1371/journal.pone.0220007,PMC6655660,31339911,CC BY,"Extracellular vesicles (EVs) are thought to be important in cell-cell communication and have elicited extraordinary interest as potential biomarkers of disease. However, quantitative methods to enable elucidation of mechanisms underlying release are few. Here, we describe a cell-based assay for monitoring EV release using the EV-enriched tetraspanin CD63 fused to the small, ATP-independent reporter enzyme, Nanoluciferase. Release of CD63-containing EVs from stably expressing cell lines was monitored by comparing luciferase activity in culture media to that remaining in cells. HEK293, U2OS, U87 and SKMel28 cells released 0.3%-0.6% of total cellular CD63 in the form of EVs over 5 hrs, varying by cell line. To identify cellular machinery important for secretion of CD63-containing EVs, we performed a screen of biologically active chemicals in HEK293 cells. While a majority of compounds did not significantly affect EV release, treating cells with the plecomacrolides bafilomycin or concanamycin, known to inhibit the V-ATPase, dramatically increased EV release. Interestingly, alkalization of the endosomal lumen using weak bases had no effect, suggesting a pH-independent enhancement of EV release by V-ATPase inhibitors. The ability to quantify EVs in small samples will enable future detailed studies of release kinetics as well as further chemical and genetic screening to define pathways involved in EV secretion.",2019 Jul 24,"['Cashikar, Anil G.', 'Hanson, Phyllis I.']",PLoS One,,,False
f91bed702f978d1d582efb5773513b8fb97460b0,PMC,A cell-based assay for CD63-containing extracellular vesicles,http://dx.doi.org/10.1371/journal.pone.0220007,PMC6655660,31339911,CC BY,"Extracellular vesicles (EVs) are thought to be important in cell-cell communication and have elicited extraordinary interest as potential biomarkers of disease. However, quantitative methods to enable elucidation of mechanisms underlying release are few. Here, we describe a cell-based assay for monitoring EV release using the EV-enriched tetraspanin CD63 fused to the small, ATP-independent reporter enzyme, Nanoluciferase. Release of CD63-containing EVs from stably expressing cell lines was monitored by comparing luciferase activity in culture media to that remaining in cells. HEK293, U2OS, U87 and SKMel28 cells released 0.3%-0.6% of total cellular CD63 in the form of EVs over 5 hrs, varying by cell line. To identify cellular machinery important for secretion of CD63-containing EVs, we performed a screen of biologically active chemicals in HEK293 cells. While a majority of compounds did not significantly affect EV release, treating cells with the plecomacrolides bafilomycin or concanamycin, known to inhibit the V-ATPase, dramatically increased EV release. Interestingly, alkalization of the endosomal lumen using weak bases had no effect, suggesting a pH-independent enhancement of EV release by V-ATPase inhibitors. The ability to quantify EVs in small samples will enable future detailed studies of release kinetics as well as further chemical and genetic screening to define pathways involved in EV secretion.",2019 Jul 24,"['Cashikar, Anil G.', 'Hanson, Phyllis I.']",PLoS One,,,False
91eed606efc0a15dd48615476f175ffbb765c455,PMC,A cell-based assay for CD63-containing extracellular vesicles,http://dx.doi.org/10.1371/journal.pone.0220007,PMC6655660,31339911,CC BY,"Extracellular vesicles (EVs) are thought to be important in cell-cell communication and have elicited extraordinary interest as potential biomarkers of disease. However, quantitative methods to enable elucidation of mechanisms underlying release are few. Here, we describe a cell-based assay for monitoring EV release using the EV-enriched tetraspanin CD63 fused to the small, ATP-independent reporter enzyme, Nanoluciferase. Release of CD63-containing EVs from stably expressing cell lines was monitored by comparing luciferase activity in culture media to that remaining in cells. HEK293, U2OS, U87 and SKMel28 cells released 0.3%-0.6% of total cellular CD63 in the form of EVs over 5 hrs, varying by cell line. To identify cellular machinery important for secretion of CD63-containing EVs, we performed a screen of biologically active chemicals in HEK293 cells. While a majority of compounds did not significantly affect EV release, treating cells with the plecomacrolides bafilomycin or concanamycin, known to inhibit the V-ATPase, dramatically increased EV release. Interestingly, alkalization of the endosomal lumen using weak bases had no effect, suggesting a pH-independent enhancement of EV release by V-ATPase inhibitors. The ability to quantify EVs in small samples will enable future detailed studies of release kinetics as well as further chemical and genetic screening to define pathways involved in EV secretion.",2019 Jul 24,"['Cashikar, Anil G.', 'Hanson, Phyllis I.']",PLoS One,,,False
c66b53fa3a31eb9fcc20c56830c89061b7caed49,PMC,Increasing the translation of mouse models of MERS coronavirus pathogenesis through kinetic hematological analysis,http://dx.doi.org/10.1371/journal.pone.0220126,PMC6655769,31339932,CC BY,"Newly emerging viral pathogens pose a constant and unpredictable threat to human and animal health. Coronaviruses (CoVs) have a penchant for sudden emergence, as evidenced by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV) and most recently, swine acute diarrhea syndrome coronavirus (SADS-CoV). Small animal models of emerging viral pathogenesis are crucial to better understand the virus and host factors driving disease progression. However, rodent models are often criticized for their limited translatability to humans. The complete blood count is the most ordered clinical test in the United States serving as the cornerstone of clinical medicine and differential diagnosis. We recently generated a mouse model for MERS-CoV pathogenesis through the humanization of the orthologous entry receptor dipeptidyl peptidase 4 (DPP4). To increase the translatability of this model, we validated and established the use of an automated veterinary hematology analyzer (VetScan HM5) at biosafety level 3 for analysis of peripheral blood. MERS-CoV lung titer peaked 2 days post infection concurrent with lymphopenia and neutrophilia in peripheral blood, two phenomena also observed in MERS-CoV infection of humans. The fluctuations in leukocyte populations measured by Vetscan HM5 were corroborated by standard flow cytometry, thus confirming the utility of this approach. Comparing a sublethal and lethal dose of MERS-CoV in mice, analysis of daily blood draws demonstrates a dose dependent modulation of leukocytes. Major leukocyte populations were modulated before weight loss was observed. Importantly, neutrophil counts on 1dpi were predictive of disease severity with a lethal dose of MERS-CoV highlighting the predictive value of hematology in this model. Taken together, the inclusion of hematological measures in mouse models of emerging viral pathogenesis increases their translatability and should elevate the preclinical evaluation of MERS-CoV therapeutics and vaccines to better mirror the complexity of the human condition.",2019 Jul 24,"['Leist, Sarah R.', 'Jensen, Kara L.', 'Baric, Ralph S.', 'Sheahan, Timothy P.']",PLoS One,,,True
2188208efc7ac8e7721dfc5cbea787d5b62c3537,PMC,Alternative conformations of a major antigenic site on RSV F,http://dx.doi.org/10.1371/journal.ppat.1007944,PMC6658013,31306469,CC BY,"The respiratory syncytial virus (RSV) fusion (F) glycoprotein is a major target of neutralizing antibodies arising from natural infection, and antibodies that specifically bind to the prefusion conformation of RSV F generally demonstrate the greatest neutralization potency. Prefusion-stabilized RSV F variants have been engineered as vaccine antigens, but crystal structures of these variants have revealed conformational differences in a key antigenic site located at the apex of the trimer, referred to as antigenic site Ø. Currently, it is unclear if flexibility in this region is an inherent property of prefusion RSV F or if it is related to inadequate stabilization of site Ø in the engineered variants. Therefore, we set out to investigate the conformational flexibility of antigenic site Ø, as well as the ability of the human immune system to recognize alternative conformations of this site, by determining crystal structures of prefusion RSV F bound to neutralizing human-derived antibodies AM22 and RSD5. Both antibodies bound with high affinity and were specific for the prefusion conformation of RSV F. Crystal structures of the complexes revealed that the antibodies recognized distinct conformations of antigenic site Ø, each diverging at a conserved proline residue located in the middle of an α-helix. These data suggest that antigenic site Ø exists as an ensemble of conformations, with individual antibodies recognizing discrete states. Collectively, these results have implications for the refolding of pneumovirus and paramyxovirus fusion proteins and should inform development of prefusion-stabilized RSV F vaccine candidates.",2019 Jul 15,"['Jones, Harrison G.', 'Battles, Michael B.', 'Lin, Chun-Chi', 'Bianchi, Siro', 'Corti, Davide', 'McLellan, Jason S.']",PLoS Pathog,,,True
a8b6b8608dfcb6b75a320c6a2661846bd152689c,PMC,The Complement Receptors C3aR and C5aR Are a New Class of Immune Checkpoint Receptor in Cancer Immunotherapy,http://dx.doi.org/10.3389/fimmu.2019.01574,PMC6658873,31379815,CC BY,"Cancer immunotherapy has made remarkable clinical advances in recent years. Antibodies targeting the immune checkpoint receptors PD-1 and CTLA-4 and adoptive cell therapy (ACT) based on ex vivo expanded peripheral CTLs, tumor infiltrating lymphocytes (TILs), gene-engineered TCR- and chimeric antigen receptor (CAR)-T cells have all shown durable clinical efficacies in multiple types of cancers. However, these immunotherapeutic approaches only benefit a small fraction of cancer patients as various immune resistance mechanisms and limitations make their effective use a challenge in the majority of cancer patients. For example, adaptive resistance to therapeutic PD-1 blockade is associated with an upregulation of some additional immune checkpoint receptors. The efficacy of transferred tumor-specific T cells under the current clinical ACT protocol is often limited by their inefficient engraftment, poor persistence, and weak capability to attack tumor cells. Recent studies demonstrate that the complement receptor C3aR and C5aR function as a new class of immune checkpoint receptors. Complement signaling through C3aR and C5aR expressed on effector T lymphocytes prevent the production of the cytokine interleukin-10 (IL-10). Removing C3aR/C5aR-mediated transcriptional suppression of IL-10 expression results in endogenous IL-10 production by antitumor effector T cells, which drives T cell expansion and enhances T cell-mediated antitumor immunity. Importantly, preclinical, and clinical data suggest that a signaling axis consisting of complement/C3aR/C5aR/IL-10 critically regulates T cell mediated antitumor immunity and manipulation of the pathway ex vivo and in vivo is an effective strategy for cancer immunotherapy. Furthermore, a combination of treatment strategies targeting the complement/C3aR/C5aR/IL-10 pathway with other treatment modalities may improve cancer therapeutic efficacy.",2019 Jul 19,"['Wang, Yu', 'Zhang, Hui', 'He, You-Wen']",Front Immunol,,,True
6dab7c67db93625257a0e3aa8a8d88f22573d1fe,PMC,Acute phase response in bovine coronavirus positive post-weaned calves with diarrhea,http://dx.doi.org/10.1186/s13028-019-0471-3,PMC6659199,31345246,CC BY,"Bovine coronavirus (BCoV) is associated with severe diarrhea in calves, winter dysentery in adult cattle, and respiratory diseases in cattle of all ages. This study aimed to investigate the relationship between white blood cell counts and haptoglobin (Hp) and serum amyloid A (SAA) levels in post-weaned calves with diarrhea caused by BCoV and those that recovered from diarrhea. Blood and fecal samples were collected twice from the same animals; 17 post-weaned calves with diarrhea (first) and 15 post-weaned calves that recovered from diarrhea (second). Real-time polymerase chain reaction revealed that all 17 fecal samples from post-weaned calves with diarrhea and one out of 15 from diarrhea-recovered calves were positive for BCoV and negative for Cryptosporidium spp., Escherichia coli K99, Salmonella spp., bovine rotavirus, and bovine viral diarrhea virus. No Eimeria oocysts were detected using the flotation method. In comparison with post-weaned calves with diarrhea, in diarrhea-recovered calves, the lymphocyte count was significantly higher (P = 0.018), and the monocyte count was significantly lower (P = 0.001); however, the number of monocytes was still high. Post-weaned calves with diarrhea had a significantly higher Hp concentration (P < 0.001) compared with diarrhea-recovered calves. The results indicated that increased Hp concentration and monocytosis but not SAA may be associated with diarrhea caused by BCoV. The present study suggests that the monitoring of Hp concentration and monocyte count is useful in the diagnosis of post-weaned calves with diarrhea caused by BCoV in this field.",2019 Jul 25,"['Chae, Jeong-Byoung', 'Park, Jinho', 'Jung, Suk-Han', 'Kang, Jin-Hee', 'Chae, Joon-Seok', 'Choi, Kyoung-Seong']",Acta Vet Scand,,,True
79641a9857d5320c10a6619c351f113b1940ce6f,PMC,"Molecular detection and genetic characterization of Mycoplasma gallisepticum, Mycoplama synoviae, and infectious bronchitis virus in poultry in Myanmar",http://dx.doi.org/10.1186/s12917-019-2018-2,PMC6659308,31345206,CC BY,"BACKGROUND: In Southeast Asian countries, including Myanmar, poultry farming is a major industry. In order to manage and maintain stable productivity, it is important to establish policies for biosecurity. Infectious respiratory diseases are a major threat to poultry farming. Avian influenza and Newcastle disease have been reported in Myanmar, but no scientific information is available for other respiratory pathogens, such as mycoplasmas and infectious bronchitis virus (IBV). Identifying the genotypes and serotypes of IBVs is especially important to inform vaccination programs. In this study, we detected Mycoplasma gallisepticum (MG), M. synoviae (MS), and IBV in several poultry farms in Myanmar. RESULTS: Samples were collected from 20 farms in three major poultry farming areas in Myanmar, and MG, MS, and IBV were detected on two, four, and eight farms, respectively, by polymerase chain reaction. Phylogenetic analysis revealed that the observed MG and MS isolates were not identical to vaccine strains. Three different genotypes of IBV were detected, but none was an unknown variant. CONCLUSIONS: Mycoplasmas and IBV were detected on poultry farms in Myanmar. Periodic surveillance is required to establish the distribution of each pathogen, and to institute better vaccine protocols.",2019 Jul 25,"['Fujisawa, Sotaro', 'Murata, Shiro', 'Takehara, Masaki', 'Katakura, Ken', 'Hmoon, Myint Myint', 'Win, Shwe Yee', 'Ohashi, Kazuhiko']",BMC Vet Res,,,True
35906518687a56bbe629ae4b4c9002b0267d8a93,PMC,Differential neurodegenerative phenotypes are associated with heterogeneous voiding dysfunction in a coronavirus-induced model of multiple sclerosis,http://dx.doi.org/10.1038/s41598-019-47407-x,PMC6659655,31350464,CC BY,"Patients with multiple sclerosis (MS) develop a variety of lower urinary tract symptoms (LUTS). We previously characterized a murine model of neurogenic bladder dysfunction induced by a neurotropic strain of a coronavirus. In the present study, we further study the role of long-lasting neurodegeneration on the development of neurogenic bladder dysfunction in mice with corona-virus induced encephalitis (CIE). Long-term follow up study revealed three phenotypes of neurodegenerative symptom development: recovery (REC group), chronic progression (C-PRO group) and chronic disease with relapsing-remitting episodes (C-RELAP group). The levels of IL-1β in REC group, IL-10 in C-RELAP group, and IL-1β, IL-6, IL-10 and TNF-α in C-PRO group were diminished in the brain. The levels of TNF-α in REC group and INF-γ, IL-2, TGF-β and TNF-α in the C-PRO group were also diminished in the urinary bladder. Mice in C-RELAP group showed a delayed recovery of voiding function. In vitro contractility studies determined a decreased basal detrusor tone and reduced amplitude of nerve-mediated contractions in C-RELAP group, whereas C-PRO group had elevated muscle-mediated contractions. In conclusion, mice with CIE developed three phenotypes of neurologic impairment mimicking different types of MS progression in humans and showed differential mechanisms driving neurogenic bladder dysfunction.",2019 Jul 26,"['Lee, Sanghee', 'Nedumaran, Balachandar', 'Hypolite, Joseph', 'Caldwell, Brian', 'Rudolph, Michael C.', 'Malykhina, Anna P.']",Sci Rep,,,True
b6f1dc149af87fc1daff699b8b599dae61773ebd,PMC,"Health in times of uncertainty in the eastern Mediterranean region, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013",http://dx.doi.org/10.1016/S2214-109X(16)30168-1,PMC6660972,27568068,CC BY,"BACKGROUND: The eastern Mediterranean region is comprised of 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen. Since our Global Burden of Disease Study 2010 (GBD 2010), the region has faced unrest as a result of revolutions, wars, and the so-called Arab uprisings. The objective of this study was to present the burden of diseases, injuries, and risk factors in the eastern Mediterranean region as of 2013. METHODS: GBD 2013 includes an annual assessment covering 188 countries from 1990 to 2013. The study covers 306 diseases and injuries, 1233 sequelae, and 79 risk factors. Our GBD 2013 analyses included the addition of new data through updated systematic reviews and through the contribution of unpublished data sources from collaborators, an updated version of modelling software, and several improvements in our methods. In this systematic analysis, we use data from GBD 2013 to analyse the burden of disease and injuries in the eastern Mediterranean region specifically. FINDINGS: The leading cause of death in the region in 2013 was ischaemic heart disease (90·3 deaths per 100 000 people), which increased by 17·2% since 1990. However, diarrhoeal diseases were the leading cause of death in Somalia (186·7 deaths per 100 000 people) in 2013, which decreased by 26·9% since 1990. The leading cause of disability-adjusted life-years (DALYs) was ischaemic heart disease for males and lower respiratory infection for females. High blood pressure was the leading risk factor for DALYs in 2013, with an increase of 83·3% since 1990. Risk factors for DALYs varied by country. In low-income countries, childhood wasting was the leading cause of DALYs in Afghanistan, Somalia, and Yemen, whereas unsafe sex was the leading cause in Djibouti. Non-communicable risk factors were the leading cause of DALYs in high-income and middle-income countries in the region. DALY risk factors varied by age, with child and maternal malnutrition affecting the younger age groups (aged 28 days to 4 years), whereas high bodyweight and systolic blood pressure affected older people (aged 60–80 years). The proportion of DALYs attributed to high body-mass index increased from 3·7% to 7·5% between 1990 and 2013. Burden of mental health problems and drug use increased. Most increases in DALYs, especially from non-communicable diseases, were due to population growth. The crises in Egypt, Yemen, Libya, and Syria have resulted in a reduction in life expectancy; life expectancy in Syria would have been 5 years higher than that recorded for females and 6 years higher for males had the crisis not occurred. INTERPRETATION: Our study shows that the eastern Mediterranean region is going through a crucial health phase. The Arab uprisings and the wars that followed, coupled with ageing and population growth, will have a major impact on the region’s health and resources. The region has historically seen improvements in life expectancy and other health indicators, even under stress. However, the current situation will cause deteriorating health conditions for many countries and for many years and will have an impact on the region and the rest of the world. Based on our findings, we call for increased investment in health in the region in addition to reducing the conflicts. FUNDING: Bill & Melinda Gates Foundation.",2016 Oct 1,"['Mokdad, Ali H', 'Forouzanfar, Mohammad Hossein', 'Daoud, Farah', 'El Bcheraoui, Charbel', 'Moradi-Lakeh, Maziar', 'Khalil, Ibrahim', 'Afshin, Ashkan', 'Tuffaha, Marwa', 'Charara, Raghid', 'Barber, Ryan M', 'Wagner, Joseph', 'Cercy, Kelly', 'Kravitz, Hannah', 'Coates, Matthew M', 'Robinson, Margaret', 'Estep, Kara', 'Steiner, Caitlyn', 'Jaber, Sara', 'Mokdad, Ali A', 'O’Rourke, Kevin F', 'Chew, Adrienne', 'Kim, Pauline', 'El Razek, Mohamed Magdy Abd', 'Abdalla, Safa', 'Abd-Allah, Foad', 'Abraham, Jerry P', 'Abu-Raddad, Laith J', 'Abu-Rmeileh, Niveen M E', 'Al-Nehmi, Abdulwahab A', 'Akanda, Ali S', 'Al Ahmadi, Hanan', 'Al Khabouri, Mazin J', 'Al Lami, Faris H', 'Al Rayess, Zulfa A', 'Alasfoor, Deena', 'AlBuhairan, Fadia S', 'Aldhahri, Saleh F', 'Alghnam, Suliman', 'Alhabib, Samia', 'Al-Hamad, Nawal', 'Ali, Raghib', 'Ali, Syed Danish', 'Alkhateeb, Mohammad', 'AlMazroa, Mohammad A', 'Alomari, Mahmoud A', 'Al-Raddadi, Rajaa', 'Alsharif, Ubai', 'Al-Sheyab, Nihaya', 'Alsowaidi, Shirina', 'Al-Thani, Mohamed', 'Altirkawi, Khalid A', 'Amare, Azmeraw T', 'Amini, Heresh', 'Ammar, Walid', 'Anwari, Palwasha', 'Asayesh, Hamid', 'Asghar, Rana', 'Assabri, Ali M', 'Assadi, Reza', 'Bacha, Umar', 'Badawi, Alaa', 'Bakfalouni, Talal', 'Basulaiman, Mohammed O', 'Bazargan-Hejazi, Shahrzad', 'Bedi, Neeraj', 'Bhakta, Amit R', 'Bhutta, Zulfiqar A', 'Abdulhak, Aref A Bin', 'Boufous, Soufiane', 'Bourne, Rupert R A', 'Danawi, Hadi', 'Das, Jai', 'Deribew, Amare', 'Ding, Eric L', 'Durrani, Adnan M', 'Elshrek, Yousef', 'Ibrahim, Mohamed E', 'Eshrati, Babak', 'Esteghamati, Alireza', 'Faghmous, Imad A D', 'Farzadfar, Farshad', 'Feigl, Andrea B', 'Fereshtehnejad, Seyed-Mohammad', 'Filip, Irina', 'Fischer, Florian', 'Gankpé, Fortuné G', 'Ginawi, Ibrahim', 'Gishu, Melkamu Dedefo', 'Gupta, Rahul', 'Habash, Rami M', 'Hafezi-Nejad, Nima', 'Hamadeh, Randah R', 'Hamdouni, Hayet', 'Hamidi, Samer', 'Harb, Hilda L', 'Hassanvand, Mohammad Sadegh', 'Hedayati, Mohammad T', 'Heydarpour, Pouria', 'Hsairi, Mohamed', 'Husseini, Abdullatif', 'Jahanmehr, Nader', 'Jha, Vivekanand', 'Jonas, Jost B', 'Karam, Nadim E', 'Kasaeian, Amir', 'Kassa, Nega Assefa', 'Kaul, Anil', 'Khader, Yousef', 'Khalifa, Shams Eldin A', 'Khan, Ejaz A', 'Khan, Gulfaraz', 'Khoja, Tawfik', 'Khosravi, Ardeshir', 'Kinfu, Yohannes', 'Defo, Barthelemy Kuate', 'Balaji, Arjun Lakshmana', 'Lunevicius, Raimundas', 'Obermeyer, Carla Makhlouf', 'Malekzadeh, Reza', 'Mansourian, Morteza', 'Marcenes, Wagner', 'Farid, Habibolah Masoudi', 'Mehari, Alem', 'Mehio-Sibai, Abla', 'Memish, Ziad A', 'Mensah, George A', 'Mohammad, Karzan A', 'Nahas, Ziad', 'Nasher, Jamal T', 'Nawaz, Haseeb', 'Nejjari, Chakib', 'Nisar, Muhammad Imran', 'Omer, Saad B', 'Parsaeian, Mahboubeh', 'Peprah, Emmanuel K', 'Pervaiz, Aslam', 'Pourmalek, Farshad', 'Qato, Dima M', 'Qorbani, Mostafa', 'Radfar, Amir', 'Rafay, Anwar', 'Rahimi, Kazem', 'Rahimi-Movaghar, Vafa', 'Rahman, Sajjad Ur', 'Rai, Rajesh K', 'Rana, Saleem M', 'Rao, Sowmya R', 'Refaat, Amany H', 'Resnikoff, Serge', 'Roshandel, Gholamreza', 'Saade, Georges', 'Saeedi, Mohammad Y', 'Sahraian, Mohammad Ali', 'Saleh, Shadi', 'Sanchez-Riera, Lidia', 'Satpathy, Maheswar', 'Sepanlou, Sadaf G', 'Setegn, Tesfaye', 'Shaheen, Amira', 'Shahraz, Saeid', 'Sheikhbahaei, Sara', 'Shishani, Kawkab', 'Sliwa, Karen', 'Tavakkoli, Mohammad', 'Terkawi, Abdullah S', 'Uthman, Olalekan A', 'Westerman, Ronny', 'Younis, Mustafa Z', 'El Sayed Zaki, Maysaa', 'Zannad, Faiez', 'Roth, Gregory A', 'Wang, Haidong', 'Naghavi, Mohsen', 'Vos, Theo', 'Al Rabeeah, Abdullah A', 'Lopez, Alan D', 'Murray, Christopher J L']",Lancet Glob Health,,,True
e4477a684773ddd26ed297e1dd0a5f297621db21,PMC,"Health in times of uncertainty in the eastern Mediterranean region, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013",http://dx.doi.org/10.1016/S2214-109X(16)30168-1,PMC6660972,27568068,CC BY,"BACKGROUND: The eastern Mediterranean region is comprised of 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen. Since our Global Burden of Disease Study 2010 (GBD 2010), the region has faced unrest as a result of revolutions, wars, and the so-called Arab uprisings. The objective of this study was to present the burden of diseases, injuries, and risk factors in the eastern Mediterranean region as of 2013. METHODS: GBD 2013 includes an annual assessment covering 188 countries from 1990 to 2013. The study covers 306 diseases and injuries, 1233 sequelae, and 79 risk factors. Our GBD 2013 analyses included the addition of new data through updated systematic reviews and through the contribution of unpublished data sources from collaborators, an updated version of modelling software, and several improvements in our methods. In this systematic analysis, we use data from GBD 2013 to analyse the burden of disease and injuries in the eastern Mediterranean region specifically. FINDINGS: The leading cause of death in the region in 2013 was ischaemic heart disease (90·3 deaths per 100 000 people), which increased by 17·2% since 1990. However, diarrhoeal diseases were the leading cause of death in Somalia (186·7 deaths per 100 000 people) in 2013, which decreased by 26·9% since 1990. The leading cause of disability-adjusted life-years (DALYs) was ischaemic heart disease for males and lower respiratory infection for females. High blood pressure was the leading risk factor for DALYs in 2013, with an increase of 83·3% since 1990. Risk factors for DALYs varied by country. In low-income countries, childhood wasting was the leading cause of DALYs in Afghanistan, Somalia, and Yemen, whereas unsafe sex was the leading cause in Djibouti. Non-communicable risk factors were the leading cause of DALYs in high-income and middle-income countries in the region. DALY risk factors varied by age, with child and maternal malnutrition affecting the younger age groups (aged 28 days to 4 years), whereas high bodyweight and systolic blood pressure affected older people (aged 60–80 years). The proportion of DALYs attributed to high body-mass index increased from 3·7% to 7·5% between 1990 and 2013. Burden of mental health problems and drug use increased. Most increases in DALYs, especially from non-communicable diseases, were due to population growth. The crises in Egypt, Yemen, Libya, and Syria have resulted in a reduction in life expectancy; life expectancy in Syria would have been 5 years higher than that recorded for females and 6 years higher for males had the crisis not occurred. INTERPRETATION: Our study shows that the eastern Mediterranean region is going through a crucial health phase. The Arab uprisings and the wars that followed, coupled with ageing and population growth, will have a major impact on the region’s health and resources. The region has historically seen improvements in life expectancy and other health indicators, even under stress. However, the current situation will cause deteriorating health conditions for many countries and for many years and will have an impact on the region and the rest of the world. Based on our findings, we call for increased investment in health in the region in addition to reducing the conflicts. FUNDING: Bill & Melinda Gates Foundation.",2016 Oct 1,"['Mokdad, Ali H', 'Forouzanfar, Mohammad Hossein', 'Daoud, Farah', 'El Bcheraoui, Charbel', 'Moradi-Lakeh, Maziar', 'Khalil, Ibrahim', 'Afshin, Ashkan', 'Tuffaha, Marwa', 'Charara, Raghid', 'Barber, Ryan M', 'Wagner, Joseph', 'Cercy, Kelly', 'Kravitz, Hannah', 'Coates, Matthew M', 'Robinson, Margaret', 'Estep, Kara', 'Steiner, Caitlyn', 'Jaber, Sara', 'Mokdad, Ali A', 'O’Rourke, Kevin F', 'Chew, Adrienne', 'Kim, Pauline', 'El Razek, Mohamed Magdy Abd', 'Abdalla, Safa', 'Abd-Allah, Foad', 'Abraham, Jerry P', 'Abu-Raddad, Laith J', 'Abu-Rmeileh, Niveen M E', 'Al-Nehmi, Abdulwahab A', 'Akanda, Ali S', 'Al Ahmadi, Hanan', 'Al Khabouri, Mazin J', 'Al Lami, Faris H', 'Al Rayess, Zulfa A', 'Alasfoor, Deena', 'AlBuhairan, Fadia S', 'Aldhahri, Saleh F', 'Alghnam, Suliman', 'Alhabib, Samia', 'Al-Hamad, Nawal', 'Ali, Raghib', 'Ali, Syed Danish', 'Alkhateeb, Mohammad', 'AlMazroa, Mohammad A', 'Alomari, Mahmoud A', 'Al-Raddadi, Rajaa', 'Alsharif, Ubai', 'Al-Sheyab, Nihaya', 'Alsowaidi, Shirina', 'Al-Thani, Mohamed', 'Altirkawi, Khalid A', 'Amare, Azmeraw T', 'Amini, Heresh', 'Ammar, Walid', 'Anwari, Palwasha', 'Asayesh, Hamid', 'Asghar, Rana', 'Assabri, Ali M', 'Assadi, Reza', 'Bacha, Umar', 'Badawi, Alaa', 'Bakfalouni, Talal', 'Basulaiman, Mohammed O', 'Bazargan-Hejazi, Shahrzad', 'Bedi, Neeraj', 'Bhakta, Amit R', 'Bhutta, Zulfiqar A', 'Abdulhak, Aref A Bin', 'Boufous, Soufiane', 'Bourne, Rupert R A', 'Danawi, Hadi', 'Das, Jai', 'Deribew, Amare', 'Ding, Eric L', 'Durrani, Adnan M', 'Elshrek, Yousef', 'Ibrahim, Mohamed E', 'Eshrati, Babak', 'Esteghamati, Alireza', 'Faghmous, Imad A D', 'Farzadfar, Farshad', 'Feigl, Andrea B', 'Fereshtehnejad, Seyed-Mohammad', 'Filip, Irina', 'Fischer, Florian', 'Gankpé, Fortuné G', 'Ginawi, Ibrahim', 'Gishu, Melkamu Dedefo', 'Gupta, Rahul', 'Habash, Rami M', 'Hafezi-Nejad, Nima', 'Hamadeh, Randah R', 'Hamdouni, Hayet', 'Hamidi, Samer', 'Harb, Hilda L', 'Hassanvand, Mohammad Sadegh', 'Hedayati, Mohammad T', 'Heydarpour, Pouria', 'Hsairi, Mohamed', 'Husseini, Abdullatif', 'Jahanmehr, Nader', 'Jha, Vivekanand', 'Jonas, Jost B', 'Karam, Nadim E', 'Kasaeian, Amir', 'Kassa, Nega Assefa', 'Kaul, Anil', 'Khader, Yousef', 'Khalifa, Shams Eldin A', 'Khan, Ejaz A', 'Khan, Gulfaraz', 'Khoja, Tawfik', 'Khosravi, Ardeshir', 'Kinfu, Yohannes', 'Defo, Barthelemy Kuate', 'Balaji, Arjun Lakshmana', 'Lunevicius, Raimundas', 'Obermeyer, Carla Makhlouf', 'Malekzadeh, Reza', 'Mansourian, Morteza', 'Marcenes, Wagner', 'Farid, Habibolah Masoudi', 'Mehari, Alem', 'Mehio-Sibai, Abla', 'Memish, Ziad A', 'Mensah, George A', 'Mohammad, Karzan A', 'Nahas, Ziad', 'Nasher, Jamal T', 'Nawaz, Haseeb', 'Nejjari, Chakib', 'Nisar, Muhammad Imran', 'Omer, Saad B', 'Parsaeian, Mahboubeh', 'Peprah, Emmanuel K', 'Pervaiz, Aslam', 'Pourmalek, Farshad', 'Qato, Dima M', 'Qorbani, Mostafa', 'Radfar, Amir', 'Rafay, Anwar', 'Rahimi, Kazem', 'Rahimi-Movaghar, Vafa', 'Rahman, Sajjad Ur', 'Rai, Rajesh K', 'Rana, Saleem M', 'Rao, Sowmya R', 'Refaat, Amany H', 'Resnikoff, Serge', 'Roshandel, Gholamreza', 'Saade, Georges', 'Saeedi, Mohammad Y', 'Sahraian, Mohammad Ali', 'Saleh, Shadi', 'Sanchez-Riera, Lidia', 'Satpathy, Maheswar', 'Sepanlou, Sadaf G', 'Setegn, Tesfaye', 'Shaheen, Amira', 'Shahraz, Saeid', 'Sheikhbahaei, Sara', 'Shishani, Kawkab', 'Sliwa, Karen', 'Tavakkoli, Mohammad', 'Terkawi, Abdullah S', 'Uthman, Olalekan A', 'Westerman, Ronny', 'Younis, Mustafa Z', 'El Sayed Zaki, Maysaa', 'Zannad, Faiez', 'Roth, Gregory A', 'Wang, Haidong', 'Naghavi, Mohsen', 'Vos, Theo', 'Al Rabeeah, Abdullah A', 'Lopez, Alan D', 'Murray, Christopher J L']",Lancet Glob Health,,,True
9c85b0dd795a95e53b5cdc4b3bc8c46d1bd5e154,PMC,Prevalence and molecular characterization of infectious bronchitis virus isolated from chicken in Bangladesh,http://dx.doi.org/10.14202/vetworld.2019.909-915,PMC6661485,31440013,CC BY,"AIM: The present study was aimed to determine the prevalence of infectious bronchitis virus (IBV) as well as virus isolation, identification, and molecular characterization of various strains circulating in Bangladesh. MATERIALS AND METHODS: A total of 371 swabs and organ samples were collected from four types of chicken including layer, Sonali (local), broiler, and broiler breeder under eight districts (Rangpur, Bogura, Tangail, Dhaka, Gazipur, Mymensingh, Jamalpur, and Cumilla) during 2014-2016 in Bangladesh. RESULTS: Out of 371 samples, 65 samples were positive in reverse transcriptase polymerase chain reaction (RT-PCR) for molecular identification of IBV. The overall prevalence was 17.52% recorded and among the selected types of chicken, the highest prevalence of IBV was found in layer that was 42.22% followed by 17.24% in Sonali, 14.93% in broiler breeder, and lowest prevalence was 11.94% in broiler chicken, respectively. Moreover, the prevalence of IBV was recorded highest in aged chicken at 41-60 weeks, which was 54.55% in layer, 27.27% in Sonali, and, afterward, 14.68% was found in broiler breeder, respectively. Frequency of IBV more frequently in winter (22.67%) followed by rainy (15.87%) and summer season (11.58%). The highest prevalence of IBV was found Tangail district (41.67%) followed by Mymensingh (24.42%), Gazipur (19.32%), Dhaka (15.38%), Jamalpur (16.67%), Bogura (13.68%), Cumilla (5.88%), and Rangpur (9.26%), respectively. Samples that were found high positive in IBV RT-PCR (Ct value below 30) were subjected to inoculation into chicken egg embryo to observe characteristic changes in chicken embryo. Swabs and organ samples were processed and passaged in 9-day-old embryonated chicken eggs through allantoic cavity route. IBV virus suspected samples inoculated into chicken egg embryos after 3-5 passages showed dwarfing and curling of the embryos which are characteristic lesions of IBV. Allantoic fluid was collected from all inoculated eggs and performed partial sequencing of S1 gene for three isolates. After sequencing, the phylogenetic tree was constructed from the nucleotide sequences of IBV isolates. Two of the isolates are 4/91 IBV and another one matched with QX-like IBV. CONCLUSION: The results revealed that the three isolates from different places in Bangladesh were identified for the 1(st) time as which will help for IBV control strategy.",2019 Jun 28,"['Bhuiyan, Zafar Ahmed', 'Ali, Md. Zulfekar', 'Moula, Mohammad Moktader', 'Giasuddin, Md.', 'Khan, Zahed Uddin Mahmood']",Vet World,,,True
7a784ba89463c11f89c9a297dd0e980b2d27c5c5,PMC,Divergent Peptide Presentations of HLA-A(*)30 Alleles Revealed by Structures With Pathogen Peptides,http://dx.doi.org/10.3389/fimmu.2019.01709,PMC6664060,31396224,CC BY,"Human leukocyte antigen (HLA) alleles have a high degree of polymorphism, which determines their peptide-binding motifs and subsequent T-cell receptor recognition. The simplest way to understand the cross-presentation of peptides by different alleles is to classify these alleles into supertypes. A1 and A3 HLA supertypes are widely distributed in humans. However, direct structural and functional evidence for peptide presentation features of key alleles (e.g., HLA-A(*)30:01 and -A(*)30:03) are lacking. Herein, the molecular basis of peptide presentation of HLA-A(*)30:01 and -A(*)30:03 was demonstrated by crystal structure determination and thermostability measurements of complexes with T-cell epitopes from influenza virus (NP44), human immunodeficiency virus (RT313), and Mycobacterium tuberculosis (MTB). When binding to the HIV peptide, RT313, the PΩ-Lys anchoring modes of HLA-A(*)30:01, and -A(*)30:03 were similar to those of HLA-A(*)11:01 in the A3 supertype. However, HLA-A(*)30:03, but not -A(*)30:01, also showed binding with the HLA(*)01:01-favored peptide, NP44, but with a specific structural conformation. Thus, different from our previous understanding, HLA-A(*)30:01 and -A(*)30:03 have specific peptide-binding characteristics that may lead to their distinct supertype-featured binding peptide motifs. Moreover, we also found that residue 77 in the F pocket was one of the key residues for the divergent peptide presentation characteristics of HLA-A(*)30:01 and -A(*)30:03. Interchanging residue 77 between HLA-A(*)30:01 and HLA-A(*)30:03 switched their presented peptide profiles. Our results provide important recommendations for screening virus and tumor-specific peptides among the population with prevalent HLA supertypes for vaccine development and immune interventions.",2019 Jul 23,"['Zhu, Shiyan', 'Liu, Kefang', 'Chai, Yan', 'Wu, Yanan', 'Lu, Dan', 'Xiao, Wenling', 'Cheng, Hao', 'Zhao, Yingze', 'Ding, Chunming', 'Lyu, Jianxin', 'Lou, Yongliang', 'Gao, George F.', 'Liu, William J.']",Front Immunol,,,True
0c4f848837c2e8eaf750682d4195cc9076d0cef5,PMC,A nationwide survey of Leishmania infantum infection in cats and associated risk factors in Italy,http://dx.doi.org/10.1371/journal.pntd.0007594,PMC6667148,31306417,CC BY,"Though scantly investigated, Leishmania infantum infection and clinical cases of leishmaniasis in cats have been recently reported in several countries of the Mediterranean basin, with large variability in prevalence data. A major limitation in the comparability of the data available is attributed to the differences in diagnostic techniques employed and cat populations sampled. The aim of this study was to assess the prevalence of L. infantum infection in owned cats across Italy by serological and molecular tests and the identification of potential risk factors. Blood samples from 2,659 cats from northern (n = 1,543), central (n = 471) and southern (n = 645) Italy were tested for antibodies against L. infantum, by an immunofluorescence antibody test and for the parasites’ DNA, by real-time PCR. Samples were additionally screened for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) proviral DNAs. An overall cumulative L. infantum prevalence of 3.9% was recorded by serology (3.3%) and/or qPCR (0.8%), with a higher rate (10.5%) in southern Italy. The risk of L. infantum infection in cats was significantly associated to the geographical areas (South vs North and Centre; p<0.0001), age class (from 19 months to 6 years old vs ≤18 months old, p = 0.0003), neutering status (not neutered vs neutered, p = 0.0028) and FIV infection (p = 0.0051).Though the role of cats in the epidemiology of L. infantum is still debated, our findings indicate that cats are exposed to and/or infected by this protozoan, mainly in endemic regions of Italy. Hence, a standardization of procedures for a prompt diagnosis of L. infantum infection in cats and for screening cat population is crucial for a better understanding of the epidemiology of feline leishmaniasis, and of the potential role of cats in the transmission cycle of zoonotic visceral leishmaniasis.",2019 Jul 15,"['Iatta, Roberta', 'Furlanello, Tommaso', 'Colella, Vito', 'Tarallo, Viviana Domenica', 'Latrofa, Maria Stefania', 'Brianti, Emanuele', 'Trerotoli, Paolo', 'Decaro, Nicola', 'Lorusso, Eleonora', 'Schunack, Bettina', 'Mirò, Guadalupe', 'Dantas-Torres, Filipe', 'Otranto, Domenico']",PLoS Negl Trop Dis,,,True
ee632fa425607e8ff91fc3730bc0782d43ce9c0c,PMC,Techniques to Study Antigen-Specific B Cell Responses,http://dx.doi.org/10.3389/fimmu.2019.01694,PMC6667631,31396218,CC BY,"Antibodies against foreign antigens are a critical component of the overall immune response and can facilitate pathogen clearance during a primary infection and also protect against subsequent infections. Dysregulation of the antibody response can lead to an autoimmune disease, malignancy, or enhanced infection. Since the experimental delineation of a distinct B cell lineage in 1965, various methods have been developed to understand antigen-specific B cell responses in the context of autoimmune diseases, primary immunodeficiencies, infection, and vaccination. In this review, we summarize the established techniques and discuss new and emerging technologies for probing the B cell response in vitro and in vivo by taking advantage of the specificity of B cell receptor (BCR)-associated and secreted antibodies. These include ELISPOT, flow cytometry, mass cytometry, and fluorescence microscopy to identify and/or isolate primary antigen-specific B cells. We also present our approach to identify rare antigen-specific B cells using magnetic enrichment followed by flow cytometry. Once these cells are isolated, in vitro proliferation assays and adoptive transfer experiments in mice can be used to further characterize antigen-specific B cell activation, function, and fate. Transgenic mouse models of B cells targeting model antigens and of B cell signaling have also significantly advanced our understanding of antigen-specific B cell responses in vivo.",2019 Jul 24,"['Boonyaratanakornkit, Jim', 'Taylor, Justin J.']",Front Immunol,,,True
6b377682a1b0f72ead6fe21eb275ab3bd1308f21,PMC,"Naturally occurring mutations in PB1 affect influenza A virus replication fidelity, virulence, and adaptability",http://dx.doi.org/10.1186/s12929-019-0547-4,PMC6668090,31366399,CC BY,"BACKGROUND: Mutations in the PB1 subunit of RNA-dependent RNA polymerase (RdRp) of influenza A virus can affect replication fidelity. Before the influenza A/H1N1 pandemic in 2009, most human influenza A/H1N1 viruses contained the avian-associated residue, serine, at position 216 in PB1. However, near the onset of the 2009 pandemic, human viruses began to acquire the mammalian-associated residue, glycine, at PB1–216, and PB1–216G became predominant in human viruses thereafter. METHODS: Using entropy-based analysis algorithm, we have previously identified several host-specific amino-acid signatures that separated avian and swine viruses from human influenza viruses. The presence of these host-specific signatures in human influenza A/H1N1 viruses suggested that these mutations were the result of adaptive genetic evolution that enabled these influenza viruses to circumvent host barriers, which resulted in cross-species transmission. We investigated the biological impact of this natural avian-to-mammalian signature substitution at PB1–216 in human influenza A/H1N1 viruses. RESULTS: We found that PB1–216G viruses had greater mutation potential, and were more sensitive to ribavirin than PB1–216S viruses. In oseltamivir-treated HEK293 cells, PB1–216G viruses generated mutations in viral neuraminidase at a higher rate than PB1–216S viruses. By contrast, PB1–216S viruses were more virulent in mice than PB1–216G viruses. These results suggest that the PB1-S216G substitution enhances viral epidemiological fitness by increasing the frequency of adaptive mutations in human influenza A/H1N1 viruses. CONCLUSIONS: Our results thus suggest that the increased adaptability and epidemiological fitness of naturally arising human PB1–216G viruses, which have a canonical low-fidelity replicase, were the biological mechanisms underlying the replacement of PB1–216S viruses with a high-fidelity replicase following the emergence of pdmH1N1. We think that continued surveillance of such naturally occurring PB1–216 variants among others is warranted to assess the potential impact of changes in RdRp fidelity on the adaptability and epidemiological fitness of human A/H1N1 influenza viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12929-019-0547-4) contains supplementary material, which is available to authorized users.",2019 Jul 31,"['Lin, Ruey-Wen', 'Chen, Guang-Wu', 'Sung, Hsiang-Hsuan', 'Lin, Ren-Jye', 'Yen, Li-Chen', 'Tseng, Yu-Ling', 'Chang, Yung-Kun', 'Lien, Shu-Pei', 'Shih, Shin-Ru', 'Liao, Ching-Len']",J Biomed Sci,,,True
69cf21ea0c191cb1ea580856df13fea7b1608b00,PMC,"HATRIC: a study of Pelargonium sidoides root extract EPs®7630 (Kaloba®) for the treatment of acute cough due to lower respiratory tract infection in adults—study protocol for a double blind, placebo-controlled randomised feasibility trial",http://dx.doi.org/10.1186/s40814-019-0478-6,PMC6668164,31384480,CC BY,"BACKGROUND: Acute lower respiratory tract infection is a common acute infection managed in primary care. The current dominant management strategy in the UK is antibiotics, despite widespread publicity regarding antimicrobial resistance and evidence that the small benefits of antibiotics do not outweigh the harms. There is a need to address the rising problem of antibiotic resistance by providing credible alternative strategies, which reduce symptom burden. There is sufficient evidence to recommend the use of Pelargonium sidoides root extract in order to warrant undertaking an independent clinical trial. We propose a feasibility study to demonstrate our ability to recruit and retain patients and conduct a placebo-controlled trial of Pelargonium sidoides extract EPs®7630 in lower respiratory tract infection where pneumonia is not suspected. Both the tablet and liquid formulations will be included. METHODS: The HATRIC trial is a double-blind randomised placebo-controlled feasibility study aiming to determine the potential to conduct a fully powered trial of Pelargonium sidoides root extract as an alternative to the inappropriate use of antibiotics for acute bronchitis in UK primary care. Primary care sites will be equally randomised to one of two formulation groups (tablet or liquid preparation). Additionally, within each site, patients will be evenly randomised to active or placebo treatment. Antibiotic consumption will be monitored during the trial, but the use of a delayed prescription strategy is encouraged. The target sample size for this study is 160 patients overall or 40 per arm, recruited from approximately 20 primary care sites. The analysis will be descriptive focusing on estimation with no formal comparison of groups taking place. DISCUSSION: If this trial demonstrates the feasibility of recruitment and delivery, we will seek funding for a fully powered placebo-controlled trial of Pelargonium sidoides root extract for the treatment of lower respiratory tract infections in primary care. TRIAL REGISTRATION: HATRIC was registered on the ISRCTN registry (ISRCTN17672884) on 16 August 2018.",2019 Jul 31,"['Whitehead, Amy', 'Simpson, Catherine', 'Willcox, Merlin', 'Webley, Frances', 'Hay, Alastair D.', 'Butler, Chris', 'Yao, Lily', 'Wrixon, Emma', 'Bell, Margaret', 'Bostock, Jennifer', 'Little, Paul', 'Griffiths, Gareth', 'Moore, Michael']",Pilot Feasibility Stud,,,True
c1aff1d1cda60a3215266ed6d56288d5b3630c50,PMC,Recombinant vector vaccine evolution,http://dx.doi.org/10.1371/journal.pcbi.1006857,PMC6668849,31323032,CC BY,"Replicating recombinant vector vaccines consist of a fully competent viral vector backbone engineered to express an antigen from a foreign transgene. From the perspective of viral replication, the transgene is not only dispensable but may even be detrimental. Thus vaccine revertants that delete or inactivate the transgene may evolve to dominate the vaccine virus population both during the process of manufacture of the vaccine as well as during the course of host infection. A particular concern is that this vaccine evolution could reduce its antigenicity—the immunity elicited to the transgene. We use mathematical and computational models to study vaccine evolution and immunity. These models include evolution arising during the process of manufacture, the dynamics of vaccine and revertant growth, plus innate and adaptive immunity elicited during the course of infection. Although the selective basis of vaccine evolution is easy to comprehend, the immunological consequences are not. One complication is that the opportunity for vaccine evolution is limited by the short period of within-host growth before the viral population is cleared. Even less obvious, revertant growth may only weakly interfere with vaccine growth in the host and thus have a limited effect on immunity to vaccine. Overall, we find that within-host vaccine evolution can sometimes compromise vaccine immunity, but only when the extent of evolution during vaccine manufacture is severe, and this evolution can be easily avoided or mitigated.",2019 Jul 19,"['Bull, James J.', 'Nuismer, Scott L.', 'Antia, Rustom']",PLoS Comput Biol,,,True
fbe665c9bfe566f5e862d99b0655efb7e5bec33f,PMC,Recombinant vector vaccine evolution,http://dx.doi.org/10.1371/journal.pcbi.1006857,PMC6668849,31323032,CC BY,"Replicating recombinant vector vaccines consist of a fully competent viral vector backbone engineered to express an antigen from a foreign transgene. From the perspective of viral replication, the transgene is not only dispensable but may even be detrimental. Thus vaccine revertants that delete or inactivate the transgene may evolve to dominate the vaccine virus population both during the process of manufacture of the vaccine as well as during the course of host infection. A particular concern is that this vaccine evolution could reduce its antigenicity—the immunity elicited to the transgene. We use mathematical and computational models to study vaccine evolution and immunity. These models include evolution arising during the process of manufacture, the dynamics of vaccine and revertant growth, plus innate and adaptive immunity elicited during the course of infection. Although the selective basis of vaccine evolution is easy to comprehend, the immunological consequences are not. One complication is that the opportunity for vaccine evolution is limited by the short period of within-host growth before the viral population is cleared. Even less obvious, revertant growth may only weakly interfere with vaccine growth in the host and thus have a limited effect on immunity to vaccine. Overall, we find that within-host vaccine evolution can sometimes compromise vaccine immunity, but only when the extent of evolution during vaccine manufacture is severe, and this evolution can be easily avoided or mitigated.",2019 Jul 19,"['Bull, James J.', 'Nuismer, Scott L.', 'Antia, Rustom']",PLoS Comput Biol,,,False
6f0d2ad7c969018a1eca7e34968bfdc4467ec4cc,PMC,Recombinant vector vaccine evolution,http://dx.doi.org/10.1371/journal.pcbi.1006857,PMC6668849,31323032,CC BY,"Replicating recombinant vector vaccines consist of a fully competent viral vector backbone engineered to express an antigen from a foreign transgene. From the perspective of viral replication, the transgene is not only dispensable but may even be detrimental. Thus vaccine revertants that delete or inactivate the transgene may evolve to dominate the vaccine virus population both during the process of manufacture of the vaccine as well as during the course of host infection. A particular concern is that this vaccine evolution could reduce its antigenicity—the immunity elicited to the transgene. We use mathematical and computational models to study vaccine evolution and immunity. These models include evolution arising during the process of manufacture, the dynamics of vaccine and revertant growth, plus innate and adaptive immunity elicited during the course of infection. Although the selective basis of vaccine evolution is easy to comprehend, the immunological consequences are not. One complication is that the opportunity for vaccine evolution is limited by the short period of within-host growth before the viral population is cleared. Even less obvious, revertant growth may only weakly interfere with vaccine growth in the host and thus have a limited effect on immunity to vaccine. Overall, we find that within-host vaccine evolution can sometimes compromise vaccine immunity, but only when the extent of evolution during vaccine manufacture is severe, and this evolution can be easily avoided or mitigated.",2019 Jul 19,"['Bull, James J.', 'Nuismer, Scott L.', 'Antia, Rustom']",PLoS Comput Biol,,,False
3f00db51b8b2fa846179a56402bdb545643c14d9,PMC,Ranaviruses Bind Cells from Different Species through Interaction with Heparan Sulfate,http://dx.doi.org/10.3390/v11070593,PMC6669447,31261956,CC BY,"Ranavirus cross-species infections have been documented, but the viral proteins involved in the interaction with cell receptors have not yet been identified. Here, viral cell-binding proteins and their cognate cellular receptors were investigated using two ranaviruses, Andrias davidianus ranavirus (ADRV) and Rana grylio virus (RGV), and two different cell lines, Chinese giant salamander thymus cells (GSTC) and Epithelioma papulosum cyprinid (EPC) cells. The heparan sulfate (HS) analog heparin inhibited plaque formation of ADRV and RGV in the two cell lines by more than 80% at a concentration of 5 μg/mL. In addition, enzymatic removal of cell surface HS by heparinase I markedly reduced plaque formation by both viruses and competition with heparin reduced virus-cell binding. These results indicate that cell surface HS is involved in ADRV and RGV cell binding and infection. Furthermore, recombinant viral envelope proteins ADRV-58L and RGV-53R bound heparin-Sepharose beads implying the potential that cell surface HS is involved in the initial interaction between ranaviruses and susceptible host cells. To our knowledge, this is the first report identifying cell surface HS as ranavirus binding factor and furthers understanding of interactions between ranaviruses and host cells.",2019 Jun 29,"['Ke, Fei', 'Wang, Zi-Hao', 'Ming, Cheng-Yue', 'Zhang, Qi-Ya']",Viruses,,,True
82bc247394e2e55f46bdb295bd2a3f6d19f1365b,PMC,Heparan Sulfate Proteoglycans and Viral Attachment: True Receptors or Adaptation Bias?,http://dx.doi.org/10.3390/v11070596,PMC6669472,31266258,CC BY,"Heparan sulfate proteoglycans (HSPG) are composed of unbranched, negatively charged heparan sulfate (HS) polysaccharides attached to a variety of cell surface or extracellular matrix proteins. Widely expressed, they mediate many biological activities, including angiogenesis, blood coagulation, developmental processes, and cell homeostasis. HSPG are highly sulfated and broadly used by a range of pathogens, especially viruses, to attach to the cell surface. In this review, we summarize the current knowledge on HSPG–virus interactions and distinguish viruses with established HS binding, viruses that bind HS only after intra-host or cell culture adaptation, and finally, viruses whose dependence on HS for infection is debated. We also provide an overview of the antiviral compounds designed to interfere with HS binding. Many questions remain about the true importance of these receptors in vivo, knowledge that is critical for the design of future antiviral therapies.",2019 Jul 1,"['Cagno, Valeria', 'Tseligka, Eirini D.', 'Jones, Samuel T.', 'Tapparel, Caroline']",Viruses,,,True
8e7aa7140ee7e3c82c78c1aa4cf0cb2583e8d9bd,PMC,The Nucleoprotein and Phosphoprotein of Peste des Petits Ruminants Virus Inhibit Interferons Signaling by Blocking the JAK-STAT Pathway,http://dx.doi.org/10.3390/v11070629,PMC6669484,31288481,CC BY,"Peste des petits ruminants virus (PPRV) is associated with global peste des petits ruminants resulting in severe economic loss. Peste des petits ruminants virus dampens host interferon-based signaling pathways through multiple mechanisms. Previous studies deciphered the role of V and C in abrogating IFN-β production. Moreover, V protein directly interacted with signal transducers and activators of transcription 1 (STAT1) and STAT2 resulting in the impairment of host IFN responses. In our present study, PPRV infection inhibited both IFN-β- and IFN-γ-induced activation of IFN-stimulated response element (ISRE) and IFN-γ-activated site (GAS) element, respectively. Both N and P proteins, functioning as novel IFN response antagonists, markedly suppressed IFN-β-induced ISRE and IFN-γ-induced GAS promoter activation to impair downstream upregulation of various interferon-stimulated genes (ISGs) and prevent STAT1 nuclear translocation. Specifically, P protein interacted with STAT1 and subsequently inhibited STAT1 phosphorylation, whereas N protein neither interacted with STAT1 nor inhibited STAT1 phosphorylation as well as dimerization, suggesting that the N and P protein antagonistic effects were different. Though they differed in their relationship to STAT1, both proteins blocked JAK-STAT signaling, severely negating the host antiviral immune response. Our study revealed a new mechanism employed by PPRV to evade host innate immune response, providing a platform to study the interaction of paramyxoviruses and host response.",2019 Jul 8,"['Li, Pengfei', 'Zhu, Zixiang', 'Zhang, Xiangle', 'Dang, Wen', 'Li, Linlin', 'Du, Xiaoli', 'Zhang, Miaotao', 'Wu, Chunyan', 'Xue, Qinghong', 'Liu, Xiangtao', 'Zheng, Haixue', 'Nan, Yuchen']",Viruses,,,True
d51abe791f93cef40353f149feeb961a86ae90ca,PMC,Immune Responses in the Eye-Associated Lymphoid Tissues of Chickens after Ocular Inoculation with Vaccine and Virulent Strains of the Respiratory Infectious Laryngotracheitis Virus (ILTV),http://dx.doi.org/10.3390/v11070635,PMC6669519,31295877,CC BY,"Infectious laryngotracheitis (ILT) is an acute respiratory disease of poultry caused by infectious laryngotracheitis virus (ILTV). Control of the disease with live attenuated vaccines administered via eye drop build upon immune responses generated by the eye-associated lymphoid tissues. The aim of this study was to assess cytokine and lymphocyte changes in the conjunctiva-associated lymphoid tissues (CALT) and Harderian gland (HG) stimulated by the ocular inoculation of the ILTV chicken embryo origin (CEO) vaccine strain and virulent strain 63140. This study offers strong evidence to support the roles that the CALT and HG play in the development of protective ILTV immune responses. It supports the premise that ILTV-mediated immunomodulation favors the B cell response over those of T cells. Further, it provides evidence that expansions of CD8α(+) cells, with the concomitant expression of the Granzyme A gene, are key to reducing viral genomes in the CALT and halting ILTV cytolytic replication in the conjunctiva. Ultimately, this study revealed that the early upregulation of interleukin (IL)-12p40 and Interferon (IFN)-γ cytokine genes, which shape the antigen-specific cell-mediated immune responses, retarded the decline of virus replication, and enhanced the development of lesions in the conjunctiva epithelium.",2019 Jul 10,"['Beltrán, Gabriela', 'Hurley, David J.', 'Gogal, Robert M.', 'Sharif, Shayan', 'Read, Leah R.', 'Williams, Susan M.', 'Jerry, Carmen F.', 'Maekawa, Daniel A.', 'García, Maricarmen']",Viruses,,,True
708330752dfbcdd2731c67c7ed3263d1a911241e,PMC,Feline Foamy Virus Infection: Characterization of Experimental Infection and Prevalence of Natural Infection in Domestic Cats with and without Chronic Kidney Disease,http://dx.doi.org/10.3390/v11070662,PMC6669521,31330990,CC BY,"Foamy viruses (FVs) are globally prevalent retroviruses that establish apparently apathogenic lifelong infections. Feline FV (FFV) has been isolated from domestic cats with concurrent diseases, including urinary syndromes. We experimentally infected five cats with FFV to study viral kinetics and tropism, peripheral blood mononuclear cell (PBMC) phenotype, urinary parameters, and histopathology. A persistent infection of primarily lymphoid tropism was detected with no evidence of immunological or hematologic perturbations. One cat with a significant negative correlation between lymphocytes and PBMC proviral load displayed an expanded FFV tissue tropism. Significantly increased blood urea nitrogen and ultrastructural kidney changes were noted in all experimentally infected cats, though chemistry parameters were not outside of normal ranges. Histopathological changes were observed in the brain, large intestine, and other tissues. In order to determine if there is an association of FFV with Chronic Kidney Disease, we additionally screened 125 Australian pet cats with and without CKD for FFV infection and found that FFV is highly prevalent in older cats, particularly in males with CKD, though this difference was not statistically significant compared to controls. Acute FFV infection was clinically silent, and while some measures indicated mild changes, there was no overt association of FFV infection with renal disease.",2019 Jul 19,"['Ledesma-Feliciano, Carmen', 'Troyer, Ryan M.', 'Zheng, Xin', 'Miller, Craig', 'Cianciolo, Rachel', 'Bordicchia, Matteo', 'Dannemiller, Nicholas', 'Gagne, Roderick', 'Beatty, Julia', 'Quimby, Jessica', 'Löchelt, Martin', 'VandeWoude, Sue']",Viruses,,,True
c8ccb9c08a1d32420a6cc0701b72e41de5307183,PMC,Feline Foamy Virus Infection: Characterization of Experimental Infection and Prevalence of Natural Infection in Domestic Cats with and without Chronic Kidney Disease,http://dx.doi.org/10.3390/v11070662,PMC6669521,31330990,CC BY,"Foamy viruses (FVs) are globally prevalent retroviruses that establish apparently apathogenic lifelong infections. Feline FV (FFV) has been isolated from domestic cats with concurrent diseases, including urinary syndromes. We experimentally infected five cats with FFV to study viral kinetics and tropism, peripheral blood mononuclear cell (PBMC) phenotype, urinary parameters, and histopathology. A persistent infection of primarily lymphoid tropism was detected with no evidence of immunological or hematologic perturbations. One cat with a significant negative correlation between lymphocytes and PBMC proviral load displayed an expanded FFV tissue tropism. Significantly increased blood urea nitrogen and ultrastructural kidney changes were noted in all experimentally infected cats, though chemistry parameters were not outside of normal ranges. Histopathological changes were observed in the brain, large intestine, and other tissues. In order to determine if there is an association of FFV with Chronic Kidney Disease, we additionally screened 125 Australian pet cats with and without CKD for FFV infection and found that FFV is highly prevalent in older cats, particularly in males with CKD, though this difference was not statistically significant compared to controls. Acute FFV infection was clinically silent, and while some measures indicated mild changes, there was no overt association of FFV infection with renal disease.",2019 Jul 19,"['Ledesma-Feliciano, Carmen', 'Troyer, Ryan M.', 'Zheng, Xin', 'Miller, Craig', 'Cianciolo, Rachel', 'Bordicchia, Matteo', 'Dannemiller, Nicholas', 'Gagne, Roderick', 'Beatty, Julia', 'Quimby, Jessica', 'Löchelt, Martin', 'VandeWoude, Sue']",Viruses,,,False
d8d257c7faebdd3d749b56befc9927d7d064e512,PMC,Anti-Respiratory Syncytial Virus Activity of Plantago asiatica and Clerodendrum trichotomum Extracts In Vitro and In Vivo,http://dx.doi.org/10.3390/v11070604,PMC6669655,31277257,CC BY,"The herbs Plantago asiatica and Clerodendrum trichotomum have been commonly used for centuries in indigenous and folk medicine in tropical and subtropical regions of the world. In this study, we show that extracts from these herbs have antiviral effects against the respiratory syncytial virus (RSV) in vitro cell cultures and an in vivo mouse model. Treatment of HEp2 cells and A549 cells with a non-cytotoxic concentration of Plantago asiatica or Clerodendrum trichotomum extract significantly reduced RSV replication, RSV-induced cell death, RSV gene transcription, RSV protein synthesis, and also blocked syncytia formation. Interestingly, oral inoculation with each herb extract significantly improved viral clearance in the lungs of BALB/c mice. Based on reported information and a high-performance liquid chromatography (HPLC) analysis, the phenolic glycoside acteoside was identified as an active chemical component of both herb extracts. An effective dose of acteoside exhibited similar antiviral effects as each herb extract against RSV in vitro and in vivo. Collectively, these results suggest that extracts of Plantago asiatica and Clerodendrum trichotomum could provide a potent natural source of an antiviral drug candidate against RSV infection.",2019 Jul 3,"['Chathuranga, Kiramage', 'Kim, Myun Soo', 'Lee, Hyun-Cheol', 'Kim, Tae-Hwan', 'Kim, Jae-Hoon', 'Gayan Chathuranga, W. A.', 'Ekanayaka, Pathum', 'Wijerathne, H. M. S. M.', 'Cho, Won-Kyung', 'Kim, Hong Ik', 'Ma, Jin Yeul', 'Lee, Jong-Soo']",Viruses,,,True
228c21cccdcae8d5b8e512fb10fade61422aa4e1,PMC,Anti-Respiratory Syncytial Virus Activity of Plantago asiatica and Clerodendrum trichotomum Extracts In Vitro and In Vivo,http://dx.doi.org/10.3390/v11070604,PMC6669655,31277257,CC BY,"The herbs Plantago asiatica and Clerodendrum trichotomum have been commonly used for centuries in indigenous and folk medicine in tropical and subtropical regions of the world. In this study, we show that extracts from these herbs have antiviral effects against the respiratory syncytial virus (RSV) in vitro cell cultures and an in vivo mouse model. Treatment of HEp2 cells and A549 cells with a non-cytotoxic concentration of Plantago asiatica or Clerodendrum trichotomum extract significantly reduced RSV replication, RSV-induced cell death, RSV gene transcription, RSV protein synthesis, and also blocked syncytia formation. Interestingly, oral inoculation with each herb extract significantly improved viral clearance in the lungs of BALB/c mice. Based on reported information and a high-performance liquid chromatography (HPLC) analysis, the phenolic glycoside acteoside was identified as an active chemical component of both herb extracts. An effective dose of acteoside exhibited similar antiviral effects as each herb extract against RSV in vitro and in vivo. Collectively, these results suggest that extracts of Plantago asiatica and Clerodendrum trichotomum could provide a potent natural source of an antiviral drug candidate against RSV infection.",2019 Jul 3,"['Chathuranga, Kiramage', 'Kim, Myun Soo', 'Lee, Hyun-Cheol', 'Kim, Tae-Hwan', 'Kim, Jae-Hoon', 'Gayan Chathuranga, W. A.', 'Ekanayaka, Pathum', 'Wijerathne, H. M. S. M.', 'Cho, Won-Kyung', 'Kim, Hong Ik', 'Ma, Jin Yeul', 'Lee, Jong-Soo']",Viruses,,,False
cfd0dbf05b77b0d303aaa222ae0f4e8d77d6f61b,PMC,MERS Coronavirus: An Emerging Zoonotic Virus,http://dx.doi.org/10.3390/v11070663,PMC6669680,31331035,CC BY,,2019 Jul 19,"['Li, Fang', 'Du, Lanying']",Viruses,,,True
d063b65a71c3bfd737e8d2b279ca2a1a171626e2,PMC,Rapid and simple colorimetric detection of multiple influenza viruses infecting humans using a reverse transcriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic platform,http://dx.doi.org/10.1186/s12879-019-4277-8,PMC6669974,31370782,CC BY,"BACKGROUND: In addition to seasonal influenza viruses recently circulating in humans, avian influenza viruses (AIVs) of H5N1, H5N6 and H7N9 subtypes have also emerged and demonstrated human infection abilities with high mortality rates. Although influenza viral infections are usually diagnosed using viral isolation and serological/molecular analyses, the cost, accessibility, and availability of these methods may limit their utility in various settings. The objective of this study was to develop and optimized a multiplex detection system for most influenza viruses currently infecting humans. METHODS: We developed and optimized a multiplex detection system for most influenza viruses currently infecting humans including two type B (both Victoria lineages and Yamagata lineages), H1N1, H3N2, H5N1, H5N6, and H7N9 using Reverse Transcriptional Loop-mediated Isothermal Amplification (RT-LAMP) technology coupled with a one-pot colorimetric visualization system to facilitate direct determination of results without additional steps. We also evaluated this multiplex RT-LAMP for clinical use using a total of 135 clinical and spiked samples (91 influenza viruses and 44 other human infectious viruses). RESULTS: We achieved rapid detection of seasonal influenza viruses (H1N1, H3N2, and Type B) and avian influenza viruses (H5N1, H5N6, H5N8 and H7N9) within an hour. The assay could detect influenza viruses with high sensitivity (i.e., from 100 to 0.1 viral genome copies), comparable to conventional RT-PCR-based approaches which would typically take several hours and require expensive equipment. This assay was capable of specifically detecting each influenza virus (Type B, H1N1, H3N2, H5N1, H5N6, H5N8 and H7N9) without cross-reactivity with other subtypes of AIVs or other human infectious viruses. Furthermore, 91 clinical and spiked samples confirmed by qRT-PCR were also detected by this multiplex RT-LAMP with 98.9% agreement. It was more sensitive than one-step RT-PCR approach (92.3%). CONCLUSIONS: Results of this study suggest that our multiplex RT-LAMP assay may provide a rapid, sensitive, cost-effective, and reliable diagnostic method for identifying recent influenza viruses infecting humans, especially in locations without access to large platforms or sophisticated equipment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-4277-8) contains supplementary material, which is available to authorized users.",2019 Aug 1,"['Ahn, Su Jeong', 'Baek, Yun Hee', 'Lloren, Khristine Kaith S.', 'Choi, Won-Suk', 'Jeong, Ju Hwan', 'Antigua, Khristine Joy C.', 'Kwon, Hyeok-il', 'Park, Su-Jin', 'Kim, Eun-Ha', 'Kim, Young-il', 'Si, Young-Jae', 'Hong, Seung Bok', 'Shin, Kyeong Seob', 'Chun, Sungkun', 'Choi, Young Ki', 'Song, Min-Suk']",BMC Infect Dis,,,False
dd12c39ca963dca8336d7f30c8842d892ec8236c,PMC,Rapid and simple colorimetric detection of multiple influenza viruses infecting humans using a reverse transcriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic platform,http://dx.doi.org/10.1186/s12879-019-4277-8,PMC6669974,31370782,CC BY,"BACKGROUND: In addition to seasonal influenza viruses recently circulating in humans, avian influenza viruses (AIVs) of H5N1, H5N6 and H7N9 subtypes have also emerged and demonstrated human infection abilities with high mortality rates. Although influenza viral infections are usually diagnosed using viral isolation and serological/molecular analyses, the cost, accessibility, and availability of these methods may limit their utility in various settings. The objective of this study was to develop and optimized a multiplex detection system for most influenza viruses currently infecting humans. METHODS: We developed and optimized a multiplex detection system for most influenza viruses currently infecting humans including two type B (both Victoria lineages and Yamagata lineages), H1N1, H3N2, H5N1, H5N6, and H7N9 using Reverse Transcriptional Loop-mediated Isothermal Amplification (RT-LAMP) technology coupled with a one-pot colorimetric visualization system to facilitate direct determination of results without additional steps. We also evaluated this multiplex RT-LAMP for clinical use using a total of 135 clinical and spiked samples (91 influenza viruses and 44 other human infectious viruses). RESULTS: We achieved rapid detection of seasonal influenza viruses (H1N1, H3N2, and Type B) and avian influenza viruses (H5N1, H5N6, H5N8 and H7N9) within an hour. The assay could detect influenza viruses with high sensitivity (i.e., from 100 to 0.1 viral genome copies), comparable to conventional RT-PCR-based approaches which would typically take several hours and require expensive equipment. This assay was capable of specifically detecting each influenza virus (Type B, H1N1, H3N2, H5N1, H5N6, H5N8 and H7N9) without cross-reactivity with other subtypes of AIVs or other human infectious viruses. Furthermore, 91 clinical and spiked samples confirmed by qRT-PCR were also detected by this multiplex RT-LAMP with 98.9% agreement. It was more sensitive than one-step RT-PCR approach (92.3%). CONCLUSIONS: Results of this study suggest that our multiplex RT-LAMP assay may provide a rapid, sensitive, cost-effective, and reliable diagnostic method for identifying recent influenza viruses infecting humans, especially in locations without access to large platforms or sophisticated equipment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-4277-8) contains supplementary material, which is available to authorized users.",2019 Aug 1,"['Ahn, Su Jeong', 'Baek, Yun Hee', 'Lloren, Khristine Kaith S.', 'Choi, Won-Suk', 'Jeong, Ju Hwan', 'Antigua, Khristine Joy C.', 'Kwon, Hyeok-il', 'Park, Su-Jin', 'Kim, Eun-Ha', 'Kim, Young-il', 'Si, Young-Jae', 'Hong, Seung Bok', 'Shin, Kyeong Seob', 'Chun, Sungkun', 'Choi, Young Ki', 'Song, Min-Suk']",BMC Infect Dis,,,True
91d5bd7d7d109d8f4ab66a54a4c6f9f5369fb19b,PMC,A step by step guide for conducting a systematic review and meta-analysis with simulation data,http://dx.doi.org/10.1186/s41182-019-0165-6,PMC6670166,31388330,CC BY,"BACKGROUND: The massive abundance of studies relating to tropical medicine and health has increased strikingly over the last few decades. In the field of tropical medicine and health, a well-conducted systematic review and meta-analysis (SR/MA) is considered a feasible solution for keeping clinicians abreast of current evidence-based medicine. Understanding of SR/MA steps is of paramount importance for its conduction. It is not easy to be done as there are obstacles that could face the researcher. To solve those hindrances, this methodology study aimed to provide a step-by-step approach mainly for beginners and junior researchers, in the field of tropical medicine and other health care fields, on how to properly conduct a SR/MA, in which all the steps here depicts our experience and expertise combined with the already well-known and accepted international guidance. We suggest that all steps of SR/MA should be done independently by 2–3 reviewers’ discussion, to ensure data quality and accuracy. CONCLUSION: SR/MA steps include the development of research question, forming criteria, search strategy, searching databases, protocol registration, title, abstract, full-text screening, manual searching, extracting data, quality assessment, data checking, statistical analysis, double data checking, and manuscript writing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s41182-019-0165-6) contains supplementary material, which is available to authorized users.",2019 Aug 1,"['Tawfik, Gehad Mohamed', 'Dila, Kadek Agus Surya', 'Mohamed, Muawia Yousif Fadlelmola', 'Tam, Dao Ngoc Hien', 'Kien, Nguyen Dang', 'Ahmed, Ali Mahmoud', 'Huy, Nguyen Tien']",Trop Med Health,,,True
6a5d030ebc7695f82f5dd6e738f9aee0d24633b3,PMC,Antiviral activity of Piscidin 1 against pseudorabies virus both in vitro and in vivo,http://dx.doi.org/10.1186/s12985-019-1199-4,PMC6670175,31366370,CC BY,"BACKGROUND: Swine-origin virus infection spreading widely could cause significant economic loss to porcine industry. Novel antiviral agents need to be developed to control this situation. METHODS: In this study, we evaluated the activities of five broad-spectrum antimicrobial peptides (AMPs) against several important swine-origin pathogenic viruses by TCID(50) assay. Plaque reduction assay and cell apoptosis assay were also used to test the activity of the peptides. Protection effect of piscidin against pseudorabies virus (PRV) was also examined in mouse model. RESULTS: Piscidin (piscidin 1), caerin (caerin 1.1) and maculatin (maculatin 1.1) could inhibit PRV by direct interaction with the virus particles in a dose-dependent manner and they could also protect the cells from PRV-induced apoptosis. Among the peptides tested, piscidin showed the strongest activity against PRV. Moreover, in vivo assay showed that piscidin can reduce the mortality of mice infected with PRV. CONCLUSION: In vitro and in vivo experiments indicate that piscidin has antiviral activity against PRV.",2019 Jul 31,"['Hu, Han', 'Guo, Nan', 'Chen, Shuhua', 'Guo, Xiaozhen', 'Liu, Xiaoli', 'Ye, Shiyi', 'Chai, Qingqing', 'Wang, Yang', 'Liu, Binlei', 'He, Qigai']",Virol J,,,True
870c8d63bfe7cbede0c0779b7991b8296dfede1c,PMC,Programmed −2/−1 Ribosomal Frameshifting in Simarteriviruses: an Evolutionarily Conserved Mechanism,http://dx.doi.org/10.1128/JVI.00370-19,PMC6675879,31167906,CC BY,"The −2/−1 programmed ribosomal frameshifting (−2/−1 PRF) mechanism in porcine reproductive and respiratory syndrome virus (PRRSV) leads to the translation of two additional viral proteins, nonstructural protein 2TF (nsp2TF) and nsp2N. This −2/−1 PRF mechanism is transactivated by a viral protein, nsp1β, and cellular poly(rC) binding proteins (PCBPs). Critical elements for −2/−1 PRF, including a slippery sequence and a downstream C-rich motif, were also identified in 11 simarteriviruses. However, the slippery sequences (XXXUCUCU instead of XXXUUUUU) in seven simarteriviruses can only facilitate −2 PRF to generate nsp2TF. The nsp1β of simian hemorrhagic fever virus (SHFV) was identified as a key factor that transactivates both −2 and −1 PRF, and the universally conserved Tyr111 and Arg114 in nsp1β are essential for this activity. In vitro translation experiments demonstrated the involvement of PCBPs in simarterivirus −2/−1 PRF. Using SHFV reverse genetics, we confirmed critical roles of nsp1β, slippery sequence, and C-rich motif in −2/−1 PRF in SHFV-infected cells. Attenuated virus growth ability was observed in SHFV mutants with impaired expression of nsp2TF and nsp2N. Comparative genomic sequence analysis showed that key elements of −2/−1 PRF are highly conserved in all known arteriviruses except equine arteritis virus (EAV) and wobbly possum disease virus (WPDV). Furthermore, −2/−1 PRF with SHFV PRF signal RNA can be stimulated by heterotypic nsp1βs of all non-EAV arteriviruses tested. Taken together, these data suggest that −2/−1 PRF is an evolutionarily conserved mechanism employed in non-EAV/-WPDV arteriviruses for the expression of additional viral proteins that are important for viral replication. IMPORTANCE Simarteriviruses are a group of arteriviruses infecting nonhuman primates, and a number of new species have been established in recent years. Although these arteriviruses are widely distributed among African nonhuman primates of different species, and some of them cause lethal hemorrhagic fever disease, this group of viruses has been undercharacterized. Since wild nonhuman primates are historically important sources or reservoirs of human pathogens, there is concern that simarteriviruses may be preemergent zoonotic pathogens. Thus, molecular characterization of simarteriviruses is becoming a priority in arterivirology. In this study, we demonstrated that an evolutionarily conserved ribosomal frameshifting mechanism is used by simarteriviruses and other distantly related arteriviruses for the expression of additional viral proteins. This mechanism is unprecedented in eukaryotic systems. Given the crucial role of ribosome function in all living systems, the potential impact of the in-depth characterization of this novel mechanism reaches beyond the field of virology.",2019 Jul 30,"['Li, Yanhua', 'Firth, Andrew E.', 'Brierley, Ian', 'Cai, Yingyun', 'Napthine, Sawsan', 'Wang, Tao', 'Yan, Xingyu', 'Kuhn, Jens H.', 'Fang, Ying']",J Virol,,,True
b94f30c95a54f9daa2912c96c63520d8e80c7146,PMC,Strengthening laboratory capacity for detection of respiratory viral pathogens through the Global Health Security Agenda (GHSA) framework,http://dx.doi.org/10.4102/ajlm.v8i1.861,PMC6676779,31392168,CC BY,"BACKGROUND: Endemic and emerging respiratory viruses are a threat to public health, and a robust public health laboratory system is essential to ensure global health security. OBJECTIVE: This program sought to expand molecular laboratory testing capacity to detect a broad range of respiratory pathogens in clinical respiratory specimens collected during disease surveillance and outbreak investigations. METHODS: As a part of the Global Health Security Agenda (GHSA), the United States Centers for Disease Control and Prevention utilised the equipment and training infrastructure already in place at the World Health Organization National Influenza Centers to expand testing capacity for respiratory viruses in laboratories in GHSA partner countries. This was done through the provision of quality assured reagents, including multiplex platforms and technical guidance for laboratory staff, as well as the assessment of laboratory testing accuracy. CONCLUSION: Early findings illustrated that GHSA laboratories have been able to expand testing capacity using specimens from routine surveillance, as well as from outbreak situations.",2019 Jul 18,"['Whitaker, Brett', 'Alroy, Karen A.', 'Guthrie, Erica', 'Schildecker, Sarah', 'Hiers, Susan', 'Woodard, Jill', 'Balajee, S. Arunmozhi']",Afr J Lab Med,,,True
2ae314588f93ab1415363034e8f6aae2fcbfbf12,PMC,Comparison of respiratory pathogen yields from Nasopharyngeal/Oropharyngeal swabs and sputum specimens collected from hospitalized adults in rural Western Kenya,http://dx.doi.org/10.1038/s41598-019-47713-4,PMC6677726,31375774,CC BY,"Molecular diagnostic methods are becoming increasingly available for assessment of acute lower respiratory illnesses (ALRI). However, nasopharyngeal/oropharyngeal (NP/OP) swabs may not accurately reflect etiologic agents from the lower respiratory tract where sputum specimens are considered as a more representative sample. The pathogen yields from NP/OP against sputum specimens have not been extensively explored, especially in tropical countries. We compared pathogen yields from NP/OP swabs and sputum specimens from patients ≥18 years hospitalized with ALRI in rural Western Kenya. Specimens were tested for 30 pathogens using TaqMan Array Cards (TAC) and results compared using McNemar’s test. The agreement for pathogen detection between NP/OP and sputum specimens ranged between 85–100%. More viruses were detected from NP/OP specimens whereas Klebsiella pneumoniae and Mycobacterium tuberculosis were more common in sputum specimens. There was no clear advantage in using sputum over NP/OP specimens to detect pathogens of ALRI in adults using TAC in the context of this tropical setting.",2019 Aug 2,"['Nyawanda, Bryan O.', 'Njuguna, Henry N.', 'Onyango, Clayton O.', 'Makokha, Caroline', 'Lidechi, Shirley', 'Fields, Barry', 'Winchell, Jonas M.', 'Katieno, Jim S.', 'Nyaundi, Jeremiah', 'Ade, Fredrick', 'Emukule, Gideon O.', 'Mott, Joshua A.', 'Otieno, Nancy', 'Widdowson, Marc-Alain', 'Chaves, Sandra S.']",Sci Rep,,,False
8e9605de5913710c88b1107fd65dcc26ab372805,PMC,Comparison of respiratory pathogen yields from Nasopharyngeal/Oropharyngeal swabs and sputum specimens collected from hospitalized adults in rural Western Kenya,http://dx.doi.org/10.1038/s41598-019-47713-4,PMC6677726,31375774,CC BY,"Molecular diagnostic methods are becoming increasingly available for assessment of acute lower respiratory illnesses (ALRI). However, nasopharyngeal/oropharyngeal (NP/OP) swabs may not accurately reflect etiologic agents from the lower respiratory tract where sputum specimens are considered as a more representative sample. The pathogen yields from NP/OP against sputum specimens have not been extensively explored, especially in tropical countries. We compared pathogen yields from NP/OP swabs and sputum specimens from patients ≥18 years hospitalized with ALRI in rural Western Kenya. Specimens were tested for 30 pathogens using TaqMan Array Cards (TAC) and results compared using McNemar’s test. The agreement for pathogen detection between NP/OP and sputum specimens ranged between 85–100%. More viruses were detected from NP/OP specimens whereas Klebsiella pneumoniae and Mycobacterium tuberculosis were more common in sputum specimens. There was no clear advantage in using sputum over NP/OP specimens to detect pathogens of ALRI in adults using TAC in the context of this tropical setting.",2019 Aug 2,"['Nyawanda, Bryan O.', 'Njuguna, Henry N.', 'Onyango, Clayton O.', 'Makokha, Caroline', 'Lidechi, Shirley', 'Fields, Barry', 'Winchell, Jonas M.', 'Katieno, Jim S.', 'Nyaundi, Jeremiah', 'Ade, Fredrick', 'Emukule, Gideon O.', 'Mott, Joshua A.', 'Otieno, Nancy', 'Widdowson, Marc-Alain', 'Chaves, Sandra S.']",Sci Rep,,,True
6f1f4714674c1dbe218971f0fcb9cd986e6f6a4f,PMC,"A Comprehensive Review of Autophagy and Its Various Roles in Infectious, Non-Infectious, and Lifestyle Diseases: Current Knowledge and Prospects for Disease Prevention, Novel Drug Design, and Therapy",http://dx.doi.org/10.3390/cells8070674,PMC6678135,31277291,CC BY,"Autophagy (self-eating) is a conserved cellular degradation process that plays important roles in maintaining homeostasis and preventing nutritional, metabolic, and infection-mediated stresses. Autophagy dysfunction can have various pathological consequences, including tumor progression, pathogen hyper-virulence, and neurodegeneration. This review describes the mechanisms of autophagy and its associations with other cell death mechanisms, including apoptosis, necrosis, necroptosis, and autosis. Autophagy has both positive and negative roles in infection, cancer, neural development, metabolism, cardiovascular health, immunity, and iron homeostasis. Genetic defects in autophagy can have pathological consequences, such as static childhood encephalopathy with neurodegeneration in adulthood, Crohn’s disease, hereditary spastic paraparesis, Danon disease, X-linked myopathy with excessive autophagy, and sporadic inclusion body myositis. Further studies on the process of autophagy in different microbial infections could help to design and develop novel therapeutic strategies against important pathogenic microbes. This review on the progress and prospects of autophagy research describes various activators and suppressors, which could be used to design novel intervention strategies against numerous diseases and develop therapeutic drugs to protect human and animal health.",2019 Jul 3,"['Khandia, Rekha', 'Dadar, Maryam', 'Munjal, Ashok', 'Dhama, Kuldeep', 'Karthik, Kumaragurubaran', 'Tiwari, Ruchi', 'Yatoo, Mohd. Iqbal', 'Iqbal, Hafiz M.N.', 'Singh, Karam Pal', 'Joshi, Sunil K.', 'Chaicumpa, Wanpen']",Cells,,,True
9c85321b0b17004a81cb40cc67c05d8939d03f12,PMC,Chemotactic Ligands that Activate G-Protein-Coupled Formylpeptide Receptors,http://dx.doi.org/10.3390/ijms20143426,PMC6678346,31336833,CC BY,"Leukocyte infiltration is a hallmark of inflammatory responses. This process depends on the bacterial and host tissue-derived chemotactic factors interacting with G-protein-coupled seven-transmembrane receptors (GPCRs) expressed on the cell surface. Formylpeptide receptors (FPRs in human and Fprs in mice) belong to the family of chemoattractant GPCRs that are critical mediators of myeloid cell trafficking in microbial infection, inflammation, immune responses and cancer progression. Both murine Fprs and human FPRs participate in many patho-physiological processes due to their expression on a variety of cell types in addition to myeloid cells. FPR contribution to numerous pathologies is in part due to its capacity to interact with a plethora of structurally diverse chemotactic ligands. One of the murine Fpr members, Fpr2, and its endogenous agonist peptide, Cathelicidin-related antimicrobial peptide (CRAMP), control normal mouse colon epithelial growth, repair and protection against inflammation-associated tumorigenesis. Recent developments in FPR (Fpr) and ligand studies have greatly expanded the scope of these receptors and ligands in host homeostasis and disease conditions, therefore helping to establish these molecules as potential targets for therapeutic intervention.",2019 Jul 12,"['Krepel, Stacey A', 'Wang, Ji Ming']",Int J Mol Sci,,,True
7e84a68e753fa2734beff117c24743d13b021c82,PMC,"Spatiotemporal Clustering of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Incidence in Saudi Arabia, 2012–2019",http://dx.doi.org/10.3390/ijerph16142520,PMC6678379,31311073,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a great public health concern globally. Although 83% of the globally confirmed cases have emerged in Saudi Arabia, the spatiotemporal clustering of MERS-CoV incidence has not been investigated. This study analysed the spatiotemporal patterns and clusters of laboratory-confirmed MERS-CoV cases reported in Saudi Arabia between June 2012 and March 2019. Temporal, seasonal, spatial and spatiotemporal cluster analyses were performed using Kulldorff’s spatial scan statistics to determine the time period and geographical areas with the highest MERS-CoV infection risk. A strongly significant temporal cluster for MERS-CoV infection risk was identified between April 5 and May 24, 2014. Most MERS-CoV infections occurred during the spring season (41.88%), with April and May showing significant seasonal clusters. Wadi Addawasir showed a high-risk spatial cluster for MERS-CoV infection. The most likely high-risk MERS-CoV annual spatiotemporal clusters were identified for a group of cities (n = 10) in Riyadh province between 2014 and 2016. A monthly spatiotemporal cluster included Jeddah, Makkah and Taif cities, with the most likely high-risk MERS-CoV infection cluster occurring between April and May 2014. Significant spatiotemporal clusters of MERS-CoV incidence were identified in Saudi Arabia. The findings are relevant to control the spread of the disease. This study provides preliminary risk assessments for the further investigation of the environmental risk factors associated with MERS-CoV clusters.",2019 Jul 15,"['Al-Ahmadi, Khalid', 'Alahmadi, Sabah', 'Al-Zahrani, Ali']",Int J Environ Res Public Health,,,True
2efa5dad7a6606eece48c0c389fdd45b2f7c90e6,PMC,Viroporins in the Influenza Virus,http://dx.doi.org/10.3390/cells8070654,PMC6679168,31261944,CC BY,"Influenza is a highly contagious virus that causes seasonal epidemics and unpredictable pandemics. Four influenza virus types have been identified to date: A, B, C and D, with only A–C known to infect humans. Influenza A and B viruses are responsible for seasonal influenza epidemics in humans and are responsible for up to a billion flu infections annually. The M2 protein is present in all influenza types and belongs to the class of viroporins, i.e., small proteins that form ion channels that increase membrane permeability in virus-infected cells. In influenza A and B, AM2 and BM2 are predominantly proton channels, although they also show some permeability to monovalent cations. By contrast, M2 proteins in influenza C and D, CM2 and DM2, appear to be especially selective for chloride ions, with possibly some permeability to protons. These differences point to different biological roles for M2 in types A and B versus C and D, which is also reflected in their sequences. AM2 is by far the best characterized viroporin, where mechanistic details and rationale of its acid activation, proton selectivity, unidirectionality, and relative low conductance are beginning to be understood. The present review summarizes the biochemical and structural aspects of influenza viroporins and discusses the most relevant aspects of function, inhibition, and interaction with the host.",2019 Jun 29,"['To, Janet', 'Torres, Jaume']",Cells,,,True
24a8a71cbe308f92fd40a91b81fd4483363bd36b,PMC,The use of biochar in animal feeding,http://dx.doi.org/10.7717/peerj.7373,PMC6679646,31396445,CC BY,"Biochar, that is, carbonized biomass similar to charcoal, has been used in acute medical treatment of animals for many centuries. Since 2010, livestock farmers increasingly use biochar as a regular feed supplement to improve animal health, increase nutrient intake efficiency and thus productivity. As biochar gets enriched with nitrogen-rich organic compounds during the digestion process, the excreted biochar-manure becomes a more valuable organic fertilizer causing lower nutrient losses and greenhouse gas emissions during storage and soil application. Scientists only recently started to investigate the mechanisms of biochar in the different stages of animal digestion and thus most published results on biochar feeding are based so far on empirical studies. This review summarizes the state of knowledge up to the year 2019 by evaluating 112 relevant scientific publications on the topic to derive initial insights, discuss potential mechanisms behind observations and identify important knowledge gaps and future research needs. The literature analysis shows that in most studies and for all investigated farm animal species, positive effects on different parameters such as toxin adsorption, digestion, blood values, feed efficiency, meat quality and/or greenhouse gas emissions could be found when biochar was added to feed. A considerable number of studies provided statistically non-significant results, though tendencies were mostly positive. Rare negative effects were identified in regard to the immobilization of liposoluble feed ingredients (e.g., vitamin E or Carotenoids) which may limit long-term biochar feeding. We found that most of the studies did not systematically investigate biochar properties (which may vastly differ) and dosage, which is a major drawback for generalizing results. Our review demonstrates that the use of biochar as a feed additive has the potential to improve animal health, feed efficiency and livestock housing climate, to reduce nutrient losses and greenhouse gas emissions, and to increase the soil organic matter content and thus soil fertility when eventually applied to soil. In combination with other good practices, co-feeding of biochar may thus have the potential to improve the sustainability of animal husbandry. However, more systematic multi-disciplinary research is definitely needed to arrive at generalizable recommendations.",2019 Jul 31,"['Schmidt, Hans-Peter', 'Hagemann, Nikolas', 'Draper, Kathleen', 'Kammann, Claudia']",PeerJ,,,True
6d304a9fd7873449676f289294df478dcbc7b53d,PMC,Discovery of novel astrovirus genotype species in small ruminants,http://dx.doi.org/10.7717/peerj.7338,PMC6679648,31396439,CC BY,"Astroviruses (AstV) are single-stranded, positive-sense RNA viruses, best known for causing diarrhea in humans and are also found in many other mammals; in those, the relevance in gastroenteritis remains unclear. Recently described neurotropic AstV showed associations with encephalitis in humans as well as in other mammals. In Switzerland, two different neurotropic AstV were identified in cattle, as well as one in a sheep. The high genetic similarity between the ovine and one of the bovine AstV strengthens the hypothesis of an interspecies transmission. In humans, AstV associated with encephalitis were found also in human stool samples, suggesting that in these patients the infection spreads from the gastrointestinal tract to the brain under certain conditions, such as immunosuppression. Whether a similar pathogenesis occurs in ruminants remains unknown. The aims of this study were (1) the investigation of the potential occurrence of neurotropic AstV in feces samples, (2) the discovery and analysis of so far unknown AstV in small ruminants and other ruminant species’ fecal samples and (3) the examination of a potential interspecies transmission of AstV. To achieve these aims, RNA extraction out of 164 fecal samples from different ruminant species was performed and all samples were screened for known neurotropic AstV occurring in Switzerland, as well as for various AstV using RT-PCR. Positive tested samples were submitted to next generation sequencing. The generated sequences were compared to nucleotide- and amino acid databases, virus properties were identified, and phylogenetic analyses as well as recombination analysis were performed. The excretion of neurotropic AstV in small ruminants’ feces could not be demonstrated, but this work suggests the first identification of AstV in goats as well as the discovery of multiple and highly diverse new genetic variants in small ruminants, which lead to a classification into novel genotype-species. Additionally, the prediction of multiple recombination events in four of five newly discovered full or almost full-length genome sequences suggests a plausible interspecies transmission. The findings point out the occurrence and fecal shedding of previously unknown AstV in sheep and goats and pave the way towards a better understanding of the diversity and transmission of AstV in small ruminants.",2019 Jul 31,"['Kauer, Ronja V.', 'Koch, Michel C.', 'Hierweger, Melanie M.', 'Werder, Simea', 'Boujon, Céline L.', 'Seuberlich, Torsten']",PeerJ,,,True
045b111f0f2584890e9271399aa93c917a496662,PMC,Etiology and Risk Factors for Mortality in an Adult Community-acquired Pneumonia Cohort in Malawi,http://dx.doi.org/10.1164/rccm.201807-1333OC,PMC6680311,30625278,CC BY,"Rationale: In the context of rapid antiretroviral therapy rollout and an increasing burden of noncommunicable diseases, there are few contemporary data describing the etiology and outcome of community-acquired pneumonia (CAP) in sub-Saharan Africa. Objectives: To describe the current etiology of CAP in Malawi and identify risk factors for mortality. Methods: We conducted a prospective observational study of adults hospitalized with CAP to a teaching hospital in Blantyre, Malawi. Etiology was defined by blood culture, Streptococcus pneumoniae urinary antigen detection, sputum mycobacterial culture and Xpert MTB/RIF, and nasopharyngeal aspirate multiplex PCR. Measurements and Main Results: In 459 patients (285 [62.1%] males; median age, 34.7 [interquartile range, 29.4–41.9] yr), 30-day mortality was 14.6% (64/439) and associated with male sex (adjusted odds ratio, 2.60 [95% confidence interval, 1.17–5.78]), symptom duration greater than 7 days (2.78 [1.40–5.54]), tachycardia (2.99 [1.48–6.06]), hypoxemia (4.40 [2.03–9.51]), and inability to stand (3.59 [1.72–7.50]). HIV was common (355/453; 78.4%), frequently newly diagnosed (124/355; 34.9%), but not associated with mortality. S. pneumoniae (98/458; 21.4%) and Mycobacterium tuberculosis (75/326; 23.0%) were the most frequently identified pathogens. Viral infection occurred in 32.6% (148/454) with influenza (40/454; 8.8%) most common. Bacterial–viral coinfection occurred in 9.1% (28/307). Detection of M. tuberculosis was associated with mortality (adjusted odds ratio, 2.44 [1.19–5.01]). Conclusions: In the antiretroviral therapy era, CAP in Malawi remains predominantly HIV associated, with a large proportion attributable to potentially vaccine-preventable pathogens. Strategies to increase early detection and treatment of tuberculosis and improve supportive care, in particular the correction of hypoxemia, should be evaluated in clinical trials to address CAP-associated mortality.",2019 Aug 1,"['Aston, Stephen J.', 'Ho, Antonia', 'Jary, Hannah', 'Huwa, Jacqueline', 'Mitchell, Tamara', 'Ibitoye, Sarah', 'Greenwood, Simon', 'Joekes, Elizabeth', 'Daire, Arthur', 'Mallewa, Jane', 'Everett, Dean', 'Nyirenda, Mulinda', 'Faragher, Brian', 'Mwandumba, Henry C.', 'Heyderman, Robert S.', 'Gordon, Stephen B.']",Am J Respir Crit Care Med,,,True
c3e92ff23f71052b519afe647c6d69f0bf1b8e0c,PMC,An Economic Analysis of the Costs Associated with Pre-Weaning Management Strategies for Dairy Heifers,http://dx.doi.org/10.3390/ani9070471,PMC6680651,31340508,CC BY,"SIMPLE SUMMARY: Rearing of replacement female calves on a dairy farm is of critical importance to maintain herd sizes, improve the genetic quality of the herd, and remain economically sustainable. A 2-year investment period is needed for replacement female heifers to grow before entering the milking herd. The management of replacements over this 2-year period can vary greatly among operations, making it difficult to compare producers’ cost to benchmark. The objective of this project was to develop a model to calculate the cost of rearing a replacement heifer from birth to weaning under different housing, milk source, allotments, and labor and health management decisions to be used as a dairy farm decision support tool. We calculated the cost for management options with general cost values. We found that the average feed cost represented 46% of the total cost while labor, and fixed and variable costs represented 33%, 9%, and 12%, respectively. The total cost increased as milk allotment increased, but cost per Kg of gain decreased. The ranges in total cost within each management scenario often exceed the difference in cost from one scenario to the next. In conclusion, variable costs have the potential to vary among operations, playing a major role in the total cost of rearing replacements from birth to weaning. ABSTRACT: Dairy calves are raised in various housing and feeding environments on dairy farms around North America. The objective of this study was to develop a simulation model to calculate the cost of raising replacement dairy heifers using different inputs that reflect different management decisions and evaluate their influence on the total cost. In this simulation, 84 calves were modeled between 0–2 months of age to reflect a 1000 heifer herd. The decisions associated with housing, liquid diet source and allowance, labor utilization, and health were calculated. Costs and biological responses were reflective of published surveys, literature, and market conditions. A 10,000-iteration economic simulation was used for each management scenario using @Risk and PrecisionTree add-ons (Palisade Corporation, Ithaca, NY, USA) to account for variation in pre-weaning mortality rate, weaning age, and disease prevalence. As milk allotment increased, total feed cost increased. Feeding calves a higher allowance of milk resulted in a lower cost per kg of gain. Average feed cost percentage of the total cost was 46% (min, max: 33%, 59%) while labor, and fixed and variable cost represented 33% (20%, 45%), 9% (2%, 12%), and 12% (10%, 14%), respectively. Total pre-weaning costs ranged from $258.56 to $582.98 per calf across all management scenarios and milk allotments.",2019 Jul 23,"['Hawkins, Anna', 'Burdine, Kenneth', 'Amaral-Phillips, Donna', 'Costa, Joao H.C.']",Animals (Basel),,,True
204a803a89944c81ecd8b50ddfb85e78db5df7f3,PMC,Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update,http://dx.doi.org/10.3390/antiox8070235,PMC6680731,31336672,CC BY,"Poultry in commercial settings are exposed to a range of stressors. A growing body of information clearly indicates that excess ROS/RNS production and oxidative stress are major detrimental consequences of the most common commercial stressors in poultry production. During evolution, antioxidant defence systems were developed in poultry to survive in an oxygenated atmosphere. They include a complex network of internally synthesised (e.g., antioxidant enzymes, (glutathione) GSH, (coenzyme Q) CoQ) and externally supplied (vitamin E, carotenoids, etc.) antioxidants. In fact, all antioxidants in the body work cooperatively as a team to maintain optimal redox balance in the cell/body. This balance is a key element in providing the necessary conditions for cell signalling, a vital process for regulation of the expression of various genes, stress adaptation and homeostasis maintenance in the body. Since ROS/RNS are considered to be important signalling molecules, their concentration is strictly regulated by the antioxidant defence network in conjunction with various transcription factors and vitagenes. In fact, activation of vitagenes via such transcription factors as Nrf2 leads to an additional synthesis of an array of protective molecules which can deal with increased ROS/RNS production. Therefore, it is a challenging task to develop a system of optimal antioxidant supplementation to help growing/productive birds maintain effective antioxidant defences and redox balance in the body. On the one hand, antioxidants, such as vitamin E, or minerals (e.g., Se, Mn, Cu and Zn) are a compulsory part of the commercial pre-mixes for poultry, and, in most cases, are adequate to meet the physiological requirements in these elements. On the other hand, due to the aforementioned commercially relevant stressors, there is a need for additional support for the antioxidant system in poultry. This new direction in improving antioxidant defences for poultry in stress conditions is related to an opportunity to activate a range of vitagenes (via Nrf2-related mechanisms: superoxide dismutase, SOD; heme oxygenase-1, HO-1; GSH and thioredoxin, or other mechanisms: Heat shock protein (HSP)/heat shock factor (HSP), sirtuins, etc.) to maximise internal AO protection and redox balance maintenance. Therefore, the development of vitagene-regulating nutritional supplements is on the agenda of many commercial companies worldwide.",2019 Jul 22,"['Surai, Peter F.', 'Kochish, Ivan I.', 'Fisinin, Vladimir I.', 'Kidd, Michael T.']",Antioxidants (Basel),,,True
bab6dd24b41528b0a321874ef4827c873846e335,PMC,Utilisation of and Attitude towards Traditional and Complementary Medicine among Ebola Survivors in Sierra Leone,http://dx.doi.org/10.3390/medicina55070387,PMC6681324,31323758,CC BY,"Background and objectives: In addition to conventional healthcare, Ebola survivors are known to seek traditional and complementary healthcare (T&CM) options to meet their healthcare needs. However, little is known about the general beliefs of Ebola survivors regarding T&CM and the impact of these beliefs in influencing their decisions around T&CM use. This study examines Ebola survivors’ attitudes towards T&CM use in Sierra Leone. Materials and Methods: We conducted a nationwide quantitative cross-sectional study of 358 Ebola survivors in Sierra Leone between January and August 2018. We used descriptive analysis, chi-square tests and backward stepwise binary logistic regression for data analysis. Results: Close to half of the survivors (n = 163, 45.5%) had used T&CM since their discharge from an Ebola treatment centre. Survivors who viewed T&CM as boosting their immune system/resistance were 3.89 times (95%CI: 1.57–9.63, p = 0.003) more likely to use T&CM than those who did not view T&CM as boosting their immune system/resistance. Additionally, survivors who viewed T&CM as having fewer side effects than conventional medicine were more likely to use T&CM [OR = 5.03 (95%CI: 1.92–13.19, p = 0.001)]. Ebola survivors were more influenced to use T&CM based on their personal experience of the effectiveness of T&CM than by clinical evidence [OR = 13.72 (95%CI: 6.10–30.84, P < 0.001)]. Ebola survivors who perceived T&CM as providing them with more control than conventional medicine over their health/body were more likely to use T&CM [OR = 4.15 (95%CI: 1.74–9.89, p = 0.001)] as opposed to those who did not perceive T&CM in this way. Conclusions: Considering the widespread use of T&CM, an understanding of Ebola survivors’ attitudes/beliefs towards T&CM is useful to healthcare providers and policymakers with regard to public education and practitioner–survivors communication, T&CM regulation and research in Sierra Leone. Ebola survivors appear to turn to T&CM not only for treatment, but also to fill gaps in conventional health care services.",2019 Jul 18,"['James, Peter Bai', 'Wardle, Jon', 'Steel, Amie', 'Adams, Jon']",Medicina (Kaunas),,,True
e53455e72c6f41b5328175d2297717fbece5c6a0,PMC,Life-threatening Development of Cardiac Tamponade in the Span of 24 Hours,http://dx.doi.org/10.5811/cpcem.2019.4.42741,PMC6682247,31403101,CC BY,"Cardiac tamponade is a medical emergency that requires immediate treatment. Caused by the development of fluid in the pericardial space, it can result in a severe decrease in cardiac output. When encountering patients with severe hypotension and tachycardia, emergency physicians must always consider the diagnosis of tamponade to facilitate prompt and effective treatment and stabilization. We report our experience with a patient who developed life-threatening cardiac tamponade within a span of less than 24 hours.",2019 Jul 1,"['Kishi, Patrick', 'Ahmad, Thaer', 'Dodd, Kenneth W.']",Clin Pract Cases Emerg Med,,,True
1aec943a21b8dc9decd07bd0039e10e5bd87ef00,PMC,"Yupingfeng polysaccharides enhances growth performance in Qingyuan partridge chicken by up‐regulating the mRNA expression of SGLT1, GLUT2 and GLUT5",http://dx.doi.org/10.1002/vms3.167,PMC6682804,30973212,CC BY,"The ban on the use of antibiotic in feed encouraged nutritionists to using alternatives to maintain growth performance and intestinal function of broilers. This study was conducted to evaluate the effects of Yupingfeng polysaccharides (YP) supplementation on growth performance and expression of SGLT1, GLUT2 and GLUT5 in Qingyuan partridge chicken. Experiment 1: a total of 540 chickens were randomly allocated to five groups with six replication. Dietary treatments were: (1) CON (control group), basal diet; (2) T1, CON + 0.5 g kg(−1) YP; (3) T2, CON + 1 g kg(−1) YP; (4) T3, CON + 2 g kg(−1) YP; (5) T4, CON + 4 g kg(−1) YP. Experiment 2, a total of 162 were randomly allocated to three groups with three replication. Dietary treatments were: (1) CON, basal diet; (2) T1, CON + 0.5 g kg(−1) YP; (3) T2, CON + 1 g kg(−1) YP. From days 1 to 14 and overall, chicken fed T1 diet had higher ADG. On day 42, there was increased villus height of jejunum in T1 group. On days 14 and 28, there was decreased villus height of duodenum and jejunum in T2 group. In duodenum, the expression of SGLT1 (days 21, 35 and 42), GLUT2 (days 7, 14, 21, 28, 35 and 42) and GLUT5 (days 7, 14, 21 and 28) was increased with YP supplementation. In jejunum, the expression of SGLT1 (days 7, 14, 21, 28 and 35), GLUT2 (days 14, 21, 28, 35 and 42) and GLUT5 (days 7, 14, 21, 28, 35 and 42) was increased with YP supplementation. In ileum, the expression of SGLT1 (days 7, 21, 35 and 42), GLUT2 (days 7, 14, 21 and 42) and GLUT5 (days 7, 14, 21, 28, 35 and 42) was increased with YP supplementation. Dietary YP supplementation improves growth performance and expression of SGLT1, GLUT2 and GLUT5 in intestine.",2019 Apr 11,"['Yin, Fuquan', 'Lan, Ruixia', 'Wu, Zhengmin', 'Wang, Zhijing', 'Wu, Haohao', 'Li, Zhiming', 'Yu, Hui', 'Zhao, Zhihui', 'Li, Hua']",Vet Med Sci,,,True
62a510dfb56136e79dbfcb424fae13b47c476635,PMC,Porcine transmissible gastroenteritis virus inhibits NF-κB activity via nonstructural protein 3 to evade host immune system,http://dx.doi.org/10.1186/s12985-019-1206-9,PMC6683377,31382996,CC BY,"BACKGROUND: Transmissible gastroenteritis virus (TGEV), a member of the family Coronaviridae, causes lethal watery diarrhea in piglets. Previous studies have revealed that the coronaviruses develop various strategies to evade the host innate immunity through the inhibition of nuclear factor kappa B (NF-κB) signaling pathway. However, the ability of TGEV to inhibit the host innate immune response by modulating the NF-κB signaling pathway is not clear. METHODS: In this study, a dual luciferase reporter assay was used to confirm the inhibition of NF-κB by TGEV infection and to identify the major viral proteins involved in the inhibition of NF-κB signaling. Real-time quantitative PCR was used to quantify the mRNA expression of inflammatory factors. The deubiquitination of Nsp3 domains and its effect on IκBα and p65 were analyzed by western blotting. The ubiquitination level of IκBα was analyzed by immunoprecipitation. RESULTS: In ST and IPEC-J2 cells, TGEV exhibited a dose-dependent inhibition of NF-κB activity. Individual TGEV protein screening revealed the high potential of non-structural protein 3 (Nsp3) to inhibit NF-κB signaling, and leading to the downregulation of the NF-κB-induced cytokine production. We demonstrated that the inhibitory effect of Nsp3 was mainly mediated through the suppression of IκBα degradation as well as the inhibition of p65 phosphorylation and nuclear translocation. Furthermore, the amino acid residues at positions 590–1,215 in Nsp3 were demonstrated to inhibit the degradation of IκBα by inhibiting the IκBα ubiquitination. CONCLUSION: TGEV infection can inhibit the activation of the NF-κB signaling pathway, which is mainly mediated by Nsp3 through the canonical pathway. The amino acid residues at positions 590–1,215 in Nsp3 compose the critical domain that mediates NF-κB inhibition. We speculate that this inhibitory effect is likely to be related to the structure of PLP2 with deubiquitinating enzyme activity of the amino acid residues at positions 590–1,215 in Nsp3. Our study provides a better understanding of the TGEV-mediated innate immune modulation and lays the basis for studies on the pathogenesis of coronavirus.",2019 Aug 5,"['Wang, Yanan', 'Sun, Aoying', 'Sun, Yu', 'Zhang, Sijia', 'Xia, Tian', 'Guo, Tiantian', 'Hao, Zhenye', 'Sun, Li', 'Jiang, Yanping', 'Qiao, Xinyuan', 'Cui, Wen', 'Tang, Lijie', 'Xu, Yigang', 'Li, Yijing', 'Wang, Li']",Virol J,,,True
dc55c16e1cfe2f794a9924f28d4b2c487316d4d2,PMC,The burden of respiratory infections among older adults in long-term care: a systematic review,http://dx.doi.org/10.1186/s12877-019-1236-6,PMC6683564,31382895,CC BY,"BACKGROUND: Respiratory infections among older adults in long-term care facilities (LTCFs) are a major global concern, yet a rigorous systematic synthesis of the literature on the burden of respiratory infections in the LTCF setting is lacking. To address the critical need for evidence regarding the global burden of respiratory infections in LTCFs, we assessed the burden of respiratory infections in LTCFs through a systematic review of the published literature. METHODS: We identified articles published between April 1964 and March 2019 through searches of PubMed (MEDLINE), EMBASE, and the Cochrane Library. Experimental and observational studies published in English that included adults aged ≥60 residing in LTCFs who were unvaccinated (to identify the natural infection burden), and that reported measures of occurrence for influenza, respiratory syncytial virus (RSV), or pneumonia were included. Disagreements about article inclusion were discussed and articles were included based on consensus. Data on study design, population, and findings were extracted from each article. Findings were synthesized qualitatively. RESULTS: A total of 1451 articles were screened for eligibility, 345 were selected for full-text review, and 26 were included. Study population mean ages ranged from 70.8 to 90.1 years. Three (12%) studies reported influenza estimates, 7 (27%) RSV, and 16 (62%) pneumonia. Eighteen (69%) studies reported incidence estimates, 7 (27%) prevalence estimates, and 1 (4%) both. Seven (27%) studies reported outbreaks. Respiratory infection incidence estimates ranged from 1.1 to 85.2% and prevalence estimates ranging from 1.4 to 55.8%. Influenza incidences ranged from 5.9 to 85.2%. RSV incidence proportions ranged from 1.1 to 13.5%. Pneumonia prevalence proportions ranged from 1.4 to 55.8% while incidence proportions ranged from 4.8 to 41.2%. CONCLUSIONS: The reported incidence and prevalence estimates of respiratory infections among older LTCF residents varied widely between published studies. The wide range of estimates offers little useful guidance for decision-making to decrease respiratory infection burden. Large, well-designed epidemiologic studies are therefore still necessary to credibly quantify the burden of respiratory infections among older adults in LTCFs, which will ultimately help inform future surveillance and intervention efforts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12877-019-1236-6) contains supplementary material, which is available to authorized users.",2019 Aug 5,"['Childs, Arielle', 'Zullo, Andrew R.', 'Joyce, Nina R.', 'McConeghy, Kevin W.', 'van Aalst, Robertus', 'Moyo, Patience', 'Bosco, Elliott', 'Mor, Vincent', 'Gravenstein, Stefan']",BMC Geriatr,,,True
c71d6e115ba17a5b6263cf65de99c7c0fa7d487a,PMC,The use and reporting of airline passenger data for infectious disease modelling: a systematic review,http://dx.doi.org/10.2807/1560-7917.ES.2019.24.31.1800216,PMC6685100,31387671,CC BY,"BACKGROUND: A variety of airline passenger data sources are used for modelling the international spread of infectious diseases. Questions exist regarding the suitability and validity of these sources. AIM: We conducted a systematic review to identify the sources of airline passenger data used for these purposes and to assess validation of the data and reproducibility of the methodology. METHODS: Articles matching our search criteria and describing a model of the international spread of human infectious disease, parameterised with airline passenger data, were identified. Information regarding type and source of airline passenger data used was collated and the studies’ reproducibility assessed. RESULTS: We identified 136 articles. The majority (n = 96) sourced data primarily used by the airline industry. Governmental data sources were used in 30 studies and data published by individual airports in four studies. Validation of passenger data was conducted in only seven studies. No study was found to be fully reproducible, although eight were partially reproducible. LIMITATIONS: By limiting the articles to international spread, articles focussed on within-country transmission even if they used relevant data sources were excluded. Authors were not contacted to clarify their methods. Searches were limited to articles in PubMed, Web of Science and Scopus. CONCLUSION: We recommend greater efforts to assess validity and biases of airline passenger data used for modelling studies, particularly when model outputs are to inform national and international public health policies. We also recommend improving reporting standards and more detailed studies on biases in commercial and open-access data to assess their reproducibility.",2019 Aug 1,"['Meslé, Margaux Marie Isabelle', 'Hall, Ian Melvyn', 'Christley, Robert Matthew', 'Leach, Steve', 'Read, Jonathan Michael']",Euro Surveill,,,True
313d6762ff0c7e18ed7af39482b04fbd2d280bc7,PMC,Exploitation of glycosylation in enveloped virus pathobiology,http://dx.doi.org/10.1016/j.bbagen.2019.05.012,PMC6686077,31121217,CC BY,"Glycosylation is a ubiquitous post-translational modification responsible for a multitude of crucial biological roles. As obligate parasites, viruses exploit host-cell machinery to glycosylate their own proteins during replication. Viral envelope proteins from a variety of human pathogens including HIV-1, influenza virus, Lassa virus, SARS, Zika virus, dengue virus, and Ebola virus have evolved to be extensively glycosylated. These host-cell derived glycans facilitate diverse structural and functional roles during the viral life-cycle, ranging from immune evasion by glycan shielding to enhancement of immune cell infection. In this review, we highlight the imperative and auxiliary roles glycans play, and how specific oligosaccharide structures facilitate these functions during viral pathogenesis. We discuss the growing efforts to exploit viral glycobiology in the development of anti-viral vaccines and therapies.",2019 Oct,"['Watanabe, Yasunori', 'Bowden, Thomas A.', 'Wilson, Ian A.', 'Crispin, Max']",Biochim Biophys Acta Gen Subj,,,False
c513fb0abb1aa50c3323e4f6d311248701f0280b,PMC,Central Nervous System Inflammatory Aggregates in the Theiler's Virus Model of Progressive Multiple Sclerosis,http://dx.doi.org/10.3389/fimmu.2019.01821,PMC6687912,31428102,CC BY,"Persistent central nervous system (CNS) inflammation, as seen in chronic infections or inflammatory demyelinating diseases such as Multiple Sclerosis (MS), results in the accumulation of various B cell subsets in the CNS, including naïve, activated, memory B cells (Bmem), and antibody secreting cells (ASC). However, factors driving heterogeneous B cell subset accumulation and antibody (Ab) production in the CNS compartment, including the contribution of ectopic lymphoid follicles (ELF), during chronic CNS inflammation remain unclear and is a major gap in our understanding of neuroinflammation. We sought to address this gap using the Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model of progressive MS. In this model, injection of the virus into susceptible mouse strains results in a persistent infection associated with demyelination and progressive disability. During chronic infection, the predominant B cell phenotypes accumulating in the CNS were isotype-switched B cells, including Bmem and ASC with naïve/early activated and transitional B cells present at low frequencies. B cell accumulation in the CNS during chronic TMEV-IDD coincided with intrathecal Ab synthesis in the cerebrospinal fluid (CSF). Mature and isotype-switched B cells predominately localized to the meninges and perivascular space, with IgG isotype-switched B cells frequently accumulating in the parenchymal space. Both mature and isotype-switched B cells and T cells occupied meningeal and perivascular spaces, with minimal evidence for spatial organization typical of ELF mimicking secondary lymphoid organs (SLO). Moreover, immunohistological analysis of immune cell aggregates revealed a lack of SLO-like ELF features, such as cell proliferation, cell death, and germinal center B cell markers. Nonetheless, flow cytometric assessment of B cells within the CNS showed enhanced expression of activation markers, including moderate upregulation of GL7 and expression of the costimulatory molecule CD80. B cell-related chemokines and trophic factors, including APRIL, BAFF, CXCL9, CXCL10, CCL19, and CXCL13, were elevated in the CNS. These results indicate that localization of heterogeneous B cell populations, including activated and isotype-switched B cell phenotypes, to the CNS and intrathecal Ab (ItAb) synthesis can occur independently of SLO-like follicles during chronic inflammatory demyelinating disease.",2019 Aug 2,"['DiSano, Krista D.', 'Royce, Darlene B.', 'Gilli, Francesca', 'Pachner, Andrew R.']",Front Immunol,,,True
99d730ff4e80cd42f0304b9d80d7d0df0689888d,PMC,Advances in Visualization Tools for Phylogenomic and Phylodynamic Studies of Viral Diseases,http://dx.doi.org/10.3389/fpubh.2019.00208,PMC6688121,31428595,CC BY,"Genomic and epidemiological monitoring have become an integral part of our response to emerging and ongoing epidemics of viral infectious diseases. Advances in high-throughput sequencing, including portable genomic sequencing at reduced costs and turnaround time, are paralleled by continuing developments in methodology to infer evolutionary histories (dynamics/patterns) and to identify factors driving viral spread in space and time. The traditionally static nature of visualizing phylogenetic trees that represent these evolutionary relationships/processes has also evolved, albeit perhaps at a slower rate. Advanced visualization tools with increased resolution assist in drawing conclusions from phylogenetic estimates and may even have potential to better inform public health and treatment decisions, but the design (and choice of what analyses are shown) is hindered by the complexity of information embedded within current phylogenetic models and the integration of available meta-data. In this review, we discuss visualization challenges for the interpretation and exploration of reconstructed histories of viral epidemics that arose from increasing volumes of sequence data and the wealth of additional data layers that can be integrated. We focus on solutions that address joint temporal and spatial visualization but also consider what the future may bring in terms of visualization and how this may become of value for the coming era of real-time digital pathogen surveillance, where actionable results and adequate intervention strategies need to be obtained within days.",2019 Aug 2,"['Theys, Kristof', 'Lemey, Philippe', 'Vandamme, Anne-Mieke', 'Baele, Guy']",Front Public Health,,,True
27ee82e4db05cf49d789f25d14660daffe743cfd,PMC,Recent Advances in the Vaccine Development Against Middle East Respiratory Syndrome-Coronavirus,http://dx.doi.org/10.3389/fmicb.2019.01781,PMC6688523,31428074,CC BY,"Middle East respiratory syndrome (MERS) is a deadly viral respiratory disease caused by MERS-coronavirus (MERS-CoV) infection. To date, there is no specific treatment proven effective against this viral disease. In addition, no vaccine has been licensed to prevent MERS-CoV infection thus far. Therefore, our current review focuses on the most recent studies in search of an effective MERS vaccine. Overall, vaccine candidates against MERS-CoV are mainly based upon the viral spike (S) protein, due to its vital role in the viral infectivity, although several studies focused on other viral proteins such as the nucleocapsid (N) protein, envelope (E) protein, and non-structural protein 16 (NSP16) have also been reported. In general, the potential vaccine candidates can be classified into six types: viral vector-based vaccine, DNA vaccine, subunit vaccine, nanoparticle-based vaccine, inactivated-whole virus vaccine and live-attenuated vaccine, which are discussed in detail. Besides, the immune responses and potential antibody dependent enhancement of MERS-CoV infection are extensively reviewed. In addition, animal models used to study MERS-CoV and evaluate the vaccine candidates are discussed intensively.",2019 Aug 2,"['Yong, Chean Yeah', 'Ong, Hui Kian', 'Yeap, Swee Keong', 'Ho, Kok Lian', 'Tan, Wen Siang']",Front Microbiol,,,True
4bc6ead9368ec84dba7c56b78624f681293e568b,PMC,Characteristics and trends of traumatic injuries in children visiting emergency departments in South Korea: A retrospective serial cross-sectional study using both nationwide-sample and single-institutional data,http://dx.doi.org/10.1371/journal.pone.0220798,PMC6688833,31398222,CC BY,"We investigated the incidences and characteristics of pediatric traumatic injuries requiring emergency department visits, through a complementary approach using both nationwide-sample and single-institutional data. Data for children (aged <15 years) identified with traumatic injuries during a 10-year period from the Korean National Health Insurance Sharing Service (n = 35,064 among 10,114,909 randomly sampled cases from the claim records of the National Health Insurance) and the authors' institute (n = 39,228) were retrospectively reviewed. The incidences and characteristics of the injuries were investigated using both datasets; additionally, detailed information regarding the injury environments was investigated using the single-institutional data. The findings were similar across both datasets. The incidence of injuries increased during the study period; the head was most commonly injured, whereas the trunk or proximal extremities were rarely injured; low-energy head injuries accounted for >50% of the cases in children aged <5 years, although the incidences of lower-extremity injuries and fractures increased in older children. Single-institutional data demonstrated that the proportion of indoor playground and trampoline-related injuries increased rapidly during the study period, and outdoor injuries and seasonal variation (with peak incidences in May and June) were more prominent in older children. Based on similarities between both datasets, the detailed results regarding pediatric traumatic injuries obtained from the single-institutional data could be generalized nationally with adequate external validity. To prevent traumatic injuries, it may be more effective to wear protective equipment covering the head and distal extremities rather than the trunk or proximal extremities; simple clothing, such as caps, could prevent many injuries in preschoolers. Among older children, safety guidelines for outdoor sports/leisure activities are needed. The increase in pediatric traumatic injuries may be partially explained by the increased availability of indoor playgrounds and installation of trampolines. Stricter adherence to the preventive guidelines is needed.",2019 Aug 9,"['Kang, Michael Seungcheol', 'Kim, Han-Soo']",PLoS One,,,True
b8b5d71242ee50c531cab2c04176241bc48fc468,PMC,Screening and Identification of a Chicken Dendritic Cell Binding Peptide by Using a Phage Display Library,http://dx.doi.org/10.3389/fimmu.2019.01853,PMC6691127,31447851,CC BY,"Dendritic cells (DCs), as antigen-presenting cells, can initiate adaptive immune responses efficiently. Although the DC-targeting strategy has attracted more attention, relevant studies on chicken are rare. Here, specific chicken bone marrow DC-binding peptides were selected using a phage display peptide library and confirmed through ELISA, flow cytometry, fluorescence microscopy, and laser confocal microscopy. The peptide candidate SPHLHTSSPWER, named SP, was fused to the infectious bursal disease virus (IBDV) structural protein and protective antigen VP2. In vitro, the expression of DC markers (CD80, CD83, CD86, DEC205, and MHCII) and some cytokines (IFN-γ, IL-12, TNF-α, IL-1β, IL-6, and CXCLi1) by VP2-SP-stimulated DCs was significantly higher than that by DCs treated with the VP2-control peptide at 4 h (p < 0.001). In addition, an oral vaccine targeting DCs was generated using chicken-borne Lactobacillus saerimneri M11 (L. sae M11) to deliver VP2 fused with SP. Anti-IBDV mucosal and humoral immune responses were induced efficiently via oral administration, resulting in higher protective efficacy in the VP2-SP group than the VP2 group. Therefore, chicken DC targeting of IBDV protective antigen VP2 delivered by L. sae provides effective immune protection in chicken. Our study may promote research on the DC-targeting strategy to enhance the effectiveness of chicken vaccines.",2019 Aug 6,"['Ma, Sunting', 'Qiao, Xinyuan', 'Xu, Yigang', 'Wang, Li', 'Zhou, Han', 'Jiang, Yanping', 'Cui, Wen', 'Huang, Xuewei', 'Wang, Xiaona', 'Tang, Lijie', 'Li, Yijing']",Front Immunol,,,True
166ac544dda68154d0cfb96da75f30e457d6eda2,PMC,Dynamics and Differences in Systemic and Local Immune Responses After Vaccination With Inactivated and Live Commercial Vaccines and Subsequent Subclinical Infection With PRRS Virus,http://dx.doi.org/10.3389/fimmu.2019.01689,PMC6691355,31447829,CC BY,"The goals of our study were to compare the immune response to different killed and modified live vaccines against PRRS virus and to monitor the antibody production and the cell mediated immunity both at the systemic and local level. In the experiment, we immunized four groups of piglets with two commercial inactivated (A1—Progressis, A2—Suivac) and two modified live vaccines (B3—Amervac, B4—Porcilis). Twenty-one days after the final vaccination, all piglets, including the control non-immunized group (C5), were i.n., infected with the Lelystad strain of PRRS virus. The serum antibody response (IgM and IgG) was the strongest in group A1 followed by two MLV (B3 and B4) groups. Locally, we demonstrated the highest level of IgG antibodies in bronchoalveolar lavages (BALF), and saliva in group A1, whereas low IgA antibody responses in BALF and feces were detected in all groups. We have found virus neutralization antibody at DPV 21 (days post vaccination) and higher levels in all groups including the control at DPI 21 (days post infection). Positive antigen specific cell-mediated response in lymphocyte transformation test (LTT) was observed in groups B3 and B4 at DPV 7 and in group B4 at DPV 21 and in all intervals after infection. The IFN-γ producing lymphocytes after antigen stimulation were found in CD4(−)CD8(+) and CD4(+)CD8(+) subsets of all immunized groups 7 days after infection. After infection, there were obvious differences in virus excretion. The virus was detected in all groups of piglets in serum, saliva, and occasionally in feces at DPI 3. Significantly lower virus load was found in groups A1 and B3 at DPI 21. Negative samples appeared at DPI 21 in B3 group in saliva. It can be concluded that antibodies after immunization and infection, and the virus after infection can be detected in all the compartments monitored. Immunization with inactivated vaccine A1—Progressis induces high levels of antibodies produced both systemically and locally. Immunization with MLV-vaccines (Amervac and Porcilis) produces sufficient antibody levels and also cell-mediated immunity. After infection virus secretion gradually decreases in group B3, indicating tendency to induce sterile immunity.",2019 Aug 6,"['Toman, Miroslav', 'Celer, Vladimir', 'Kavanová, Lenka', 'Levá, Lenka', 'Frolichova, Jitka', 'Ondráčková, Petra', 'Kudláčková, Hana', 'Nechvátalová, Kateřina', 'Salat, Jiri', 'Faldyna, Martin']",Front Immunol,,,True
6d76fbc0763d467e9109feefe43e4e52113b78f3,PMC,Target-independent high-throughput sequencing methods provide evidence that already known human viral pathogens play a main role in respiratory infections with unexplained etiology,http://dx.doi.org/10.1080/22221751.2019.1640587,PMC6691886,31335277,CC BY,"Despite the advanced PCR-based assays available, a fraction of the pediatric respiratory infections remain unexplained every epidemic season, and there is a perception that novel viruses might be present in these specimens. We systematically collected samples from a prospective cohort of pediatric patients with respiratory infections, that returned negative results by validated molecular RT–PCR assays, and studied them with a target-independent, high-throughput sequencing-based approach. We also included a matched cohort of children with no symptoms of respiratory infection, as a contrast study population. More than fifty percent of the specimens from the group of patients with unexplained respiratory infections were resolved. However, the higher rate of detection was not due to the presence of novel viruses, but to the identification of well-known viral respiratory pathogens. Our results show that already known viral pathogens are responsible for the majority of cases that remain unexplained after the epidemic season. High-throughput sequencing approaches that use pathogen-specific probes are easier to standardize because they ensure reproducible library enrichment and sequencing. In consequence, these techniques might be desirable from a regulatory standpoint for diagnostic laboratories seeking to benefit from the many advantages of these sequencing technologies.",2019 Jul 23,"['Pérez-Sautu, Unai', 'Wiley, Michael Ross', 'Iglesias-Caballero, María', 'Pozo, Francisco', 'Prieto, Karla', 'Chitty, Joseph Alex', 'García-García, María Luz', 'Calvo, Cristina', 'Casas, Inmaculada', 'Palacios, Gustavo']",Emerg Microbes Infect,,,True
d2d8c1069a0dcff2c3426bd70b34dc41dc14ad55,PMC,"Sequential, within‐season infection with influenza A (H3N2) in a usually healthy vaccinated child",http://dx.doi.org/10.1111/irv.12668,PMC6692547,,CC BY,"Cocirculation of varying influenza types, strains, and lineages allows coinfection and intra‐season sequential infection, although a same‐strain sequential infection has not been previously described. This case report describes the first known case of sequential laboratory‐confirmed influenza A (H3N2) infections in a child within one season.",2019 Sep 26,"['Temte, Jonathan L.', 'Uzicanin, Amra', 'Goss, Maureen', 'Comp, Lily', 'Temte, Emily', 'Barlow, Shari', 'Reisdorf, Erik', 'Shult, Peter', 'Wedig, Mary', 'Florek, Kelsey']",Influenza Other Respir Viruses,,,True
76928215c6c3533279239fa704b87c1d4283a205,PMC,Transcriptomic analysis of immune response to bacterial lipopolysaccharide in zebra finch (Taeniopygia guttata),http://dx.doi.org/10.1186/s12864-019-6016-3,PMC6693190,31412766,CC BY,"BACKGROUND: Despite the convergence of rapid technological advances in genomics and the maturing field of ecoimmunology, our understanding of the genes that regulate immunity in wild populations is still nascent. Previous work to assess immune function has relied upon relatively crude measures of immunocompetence. However, with next-generation RNA-sequencing, it is now possible to create a profile of gene expression in response to an immune challenge. In this study, captive zebra finch (Taeniopygia guttata; adult males) were challenged with bacterial lipopolysaccharide (LPS) or vehicle to stimulate the innate immune system. 2 hours after injection, birds were euthanized and hypothalami, spleen, and red blood cells (RBCs) were collected. Taking advantage of the fully sequenced genome of zebra finch, total RNA was isolated, sequenced, and partially annotated in these tissue/cells. RESULTS: In hypothalamus, there were 707 significantly upregulated transcripts, as well as 564 and 144 in the spleen and RBCs, respectively, relative to controls. Also, 155 transcripts in the hypothalamus, 606 in the spleen, and 61 in the RBCs were significantly downregulated. More specifically, a number of immunity-related transcripts (e.g., IL-1β, RSAD2, SOCS3) were upregulated among tissues/cells. Additionally, transcripts involved in metabolic processes (APOD, LRAT, RBP4) were downregulated. CONCLUSIONS: These results suggest a potential trade-off in expression of genes that regulate immunity and metabolism in birds challenged with LPS. This finding is consistent with a hypothermic response to LPS treatment in small birds. Unlike mammals, birds have nucleated RBCs, and these results support a novel transcriptomic response of avian RBCs to immune challenge. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-019-6016-3) contains supplementary material, which is available to authorized users.",2019 Aug 14,"['Scalf, Cassandra S.', 'Chariker, Julia H.', 'Rouchka, Eric C.', 'Ashley, Noah T.']",BMC Genomics,,,True
0c161375d1b822a44e873c134760ddb8600a550c,PMC,The Curious Case of the Nidovirus Exoribonuclease: Its Role in RNA Synthesis and Replication Fidelity,http://dx.doi.org/10.3389/fmicb.2019.01813,PMC6693484,31440227,CC BY,"Among RNA viruses, the order Nidovirales stands out for including viruses with the largest RNA genomes currently known. Nidoviruses employ a complex RNA-synthesizing machinery comprising a variety of non-structural proteins (nsps). One of the postulated drivers of the expansion of nidovirus genomes is the presence of a proofreading 3′-to-5′ exoribonuclease (ExoN) belonging to the DEDDh family. ExoN may enhance the fidelity of RNA synthesis by correcting nucleotide incorporation errors made by the RNA-dependent RNA polymerase. Here, we review our current understanding of ExoN evolution, structure, and function. Most experimental data are derived from studies of the ExoN domain of coronaviruses (CoVs), which were triggered by the bioinformatics-based identification of ExoN in the genome of severe acute respiratory syndrome coronavirus (SARS-CoV) and its relatives in 2003. Although convincing data supporting the proofreading hypothesis have been obtained, from biochemical assays and studies with CoV mutants lacking ExoN functionality, the features of ExoN from most other nidovirus families remain to be characterized. Remarkably, viable ExoN knockout mutants were obtained only for two CoVs, mouse hepatitis virus (MHV) and SARS-CoV, whose RNA synthesis and replication kinetics were mildly affected by the lack of ExoN function. In several other CoV species, ExoN inactivation was not tolerated, and knockout mutants could not be rescued when launched using a reverse genetics system. This suggests that ExoN is also critical for primary viral RNA synthesis, a property that poorly matches the profile of an enzyme that would merely boost long-term replication fidelity. In CoVs, ExoN resides in a bifunctional replicase subunit (nsp14) whose C-terminal part has (N7-guanine)-methyltransferase activity. The crystal structure of SARS-CoV nsp14 has shed light on the interplay between these two domains, and on nsp14’s interactions with nsp10, a co-factor that strongly enhances ExoN activity in vitro assays. Further elucidation of the structure-function relationships of ExoN and its interactions with other (viral and/or host) members of the CoV replication machinery will be key to understanding the enzyme’s role in viral RNA synthesis and pathogenesis, and may contribute to the design of new approaches to combat emerging nidoviruses.",2019 Aug 7,"['Ogando, Natacha S.', 'Ferron, Francois', 'Decroly, Etienne', 'Canard, Bruno', 'Posthuma, Clara C.', 'Snijder, Eric J.']",Front Microbiol,,,True
446c633eb33c9168e597b53b0c93ead24aa9d43c,PMC,Progeny Varicella-Zoster Virus Capsids Exit the Nucleus but Never Undergo Secondary Envelopment during Autophagic Flux Inhibition by Bafilomycin A1,http://dx.doi.org/10.1128/JVI.00505-19,PMC6694825,31217243,CC BY,"Varicella-zoster virus (VZV) is an alphaherpesvirus that lacks the herpesviral neurovirulence protein ICP34.5. The underlying hypothesis of this project was that inhibitors of autophagy reduce VZV infectivity. We selected the vacuolar proton ATPase inhibitor bafilomycin A1 for analysis because of its well-known antiautophagy property of impeding acidification during the late stage of autophagic flux. We documented that bafilomycin treatment from 48 to 72 h postinfection lowered VZV titers substantially (P ≤ 0.008). Because we were unable to define the site of the block in the infectious cycle by confocal microscopy, we turned to electron microscopy. Capsids were observed in the nucleus, in the perinuclear space, and in the cytoplasm adjacent to Golgi apparatus vesicles. Many of the capsids had an aberrant appearance, as has been observed previously in infections not treated with bafilomycin. In contrast to prior untreated infections, however, secondary envelopment of capsids was not seen in the trans-Golgi network, nor were prototypical enveloped particles with capsids (virions) seen in cytoplasmic vesicles after bafilomycin treatment. Instead, multiple particles with varying diameters without capsids (light particles) were seen in large virus assembly compartments near the disorganized Golgi apparatus. Bafilomycin treatment also led to increased numbers of multivesicular bodies in the cytoplasm, some of which contained remnants of the Golgi apparatus. In summary, we have defined a previously unrecognized property of bafilomycin whereby it disrupted the site of secondary envelopment of VZV capsids by altering the pH of the trans-Golgi network and thereby preventing the correct formation of virus assembly compartments. IMPORTANCE This study of VZV assembly in the presence of bafilomycin A1 emphasizes the importance of the Golgi apparatus/trans-Golgi network as a platform in the alphaherpesvirus life cycle. We have previously shown that VZV induces levels of autophagy far above the basal levels of autophagy in human skin, a major site of VZV assembly. The current study documented that bafilomycin treatment led to impaired assembly of VZV capsids after primary envelopment/de-envelopment but before secondary reenvelopment. This VZV study also complemented prior herpes simplex virus 1 and pseudorabies virus studies investigating two other inhibitors of endoplasmic reticulum (ER)/Golgi apparatus function: brefeldin A and monensin. Studies with porcine herpesvirus demonstrated that primary enveloped particles accumulated in the perinuclear space in the presence of brefeldin A, while studies with herpes simplex virus 1 documented an impaired secondary assembly of enveloped viral particles in the presence of monensin.",2019 Aug 13,"['Girsch, James H.', 'Walters, Katherine', 'Jackson, Wallen', 'Grose, Charles']",J Virol,,,True
9f106cb1aaa9ca18670f9f70c5f539b47b08429f,PMC,Progeny Varicella-Zoster Virus Capsids Exit the Nucleus but Never Undergo Secondary Envelopment during Autophagic Flux Inhibition by Bafilomycin A1,http://dx.doi.org/10.1128/JVI.00505-19,PMC6694825,31217243,CC BY,"Varicella-zoster virus (VZV) is an alphaherpesvirus that lacks the herpesviral neurovirulence protein ICP34.5. The underlying hypothesis of this project was that inhibitors of autophagy reduce VZV infectivity. We selected the vacuolar proton ATPase inhibitor bafilomycin A1 for analysis because of its well-known antiautophagy property of impeding acidification during the late stage of autophagic flux. We documented that bafilomycin treatment from 48 to 72 h postinfection lowered VZV titers substantially (P ≤ 0.008). Because we were unable to define the site of the block in the infectious cycle by confocal microscopy, we turned to electron microscopy. Capsids were observed in the nucleus, in the perinuclear space, and in the cytoplasm adjacent to Golgi apparatus vesicles. Many of the capsids had an aberrant appearance, as has been observed previously in infections not treated with bafilomycin. In contrast to prior untreated infections, however, secondary envelopment of capsids was not seen in the trans-Golgi network, nor were prototypical enveloped particles with capsids (virions) seen in cytoplasmic vesicles after bafilomycin treatment. Instead, multiple particles with varying diameters without capsids (light particles) were seen in large virus assembly compartments near the disorganized Golgi apparatus. Bafilomycin treatment also led to increased numbers of multivesicular bodies in the cytoplasm, some of which contained remnants of the Golgi apparatus. In summary, we have defined a previously unrecognized property of bafilomycin whereby it disrupted the site of secondary envelopment of VZV capsids by altering the pH of the trans-Golgi network and thereby preventing the correct formation of virus assembly compartments. IMPORTANCE This study of VZV assembly in the presence of bafilomycin A1 emphasizes the importance of the Golgi apparatus/trans-Golgi network as a platform in the alphaherpesvirus life cycle. We have previously shown that VZV induces levels of autophagy far above the basal levels of autophagy in human skin, a major site of VZV assembly. The current study documented that bafilomycin treatment led to impaired assembly of VZV capsids after primary envelopment/de-envelopment but before secondary reenvelopment. This VZV study also complemented prior herpes simplex virus 1 and pseudorabies virus studies investigating two other inhibitors of endoplasmic reticulum (ER)/Golgi apparatus function: brefeldin A and monensin. Studies with porcine herpesvirus demonstrated that primary enveloped particles accumulated in the perinuclear space in the presence of brefeldin A, while studies with herpes simplex virus 1 documented an impaired secondary assembly of enveloped viral particles in the presence of monensin.",2019 Aug 13,"['Girsch, James H.', 'Walters, Katherine', 'Jackson, Wallen', 'Grose, Charles']",J Virol,,,False
c8f6c26a8275c6cbbeb30dc984f058902455ed52,PMC,Rational Design of Zika Virus Subunit Vaccine with Enhanced Efficacy,http://dx.doi.org/10.1128/JVI.02187-18,PMC6694833,31189716,CC BY,"Zika virus (ZIKV) infection in pregnant women can lead to fetal deaths and malformations. We have previously reported that ZIKV envelope protein domain III (EDIII) is a subunit vaccine candidate with cross-neutralization activity; however, like many other subunit vaccines, its efficacy is limited. To improve the efficacy of this subunit vaccine, we identified a nonneutralizing epitope on ZIKV EDIII surrounding residue 375, which is buried in the full-length envelope protein but becomes exposed in recombinant EDIII. We then shielded this epitope with an engineered glycan probe. Compared to the wild-type EDIII, the mutant EDIII induced significantly stronger neutralizing antibodies in three mouse strains and also demonstrated significantly improved efficacy by fully protecting mice, particularly pregnant mice and their fetuses, against high-dose lethal ZIKV challenge. Moreover, the mutant EDIII immune sera significantly enhanced the passive protective efficacy by fully protecting mice against lethal ZIKV challenge; this passive protection was positively associated with neutralizing antibody titers. We further showed that the enhanced efficacy of the mutant EDIII was due to the shielding of the immunodominant nonneutralizing epitope surrounding residue 375, which led to immune refocusing on the neutralizing epitopes. Taken together, the results of this study reveal that an intrinsic limitation of subunit vaccines is their artificially exposed immunodominant nonneutralizing epitopes, which can be overcome through glycan shielding. Additionally, the mutant ZIKV protein generated in this study is a promising subunit vaccine candidate with high efficacy in preventing ZIKV infections in mice. IMPORTANCE Viral subunit vaccines generally show low efficacy. In this study, we revealed an intrinsic limitation of subunit vaccine designs: artificially exposed surfaces of subunit vaccines contain epitopes unfavorable for vaccine efficacy. More specifically, we identified an epitope on Zika virus (ZIKV) envelope protein domain III (EDIII) that is buried in the full-length envelope protein but becomes exposed in recombinant EDIII. We further shielded this epitope with a glycan, and the resulting mutant EDIII vaccine demonstrated significantly enhanced efficacy over the wild-type EDIII vaccine in protecting animal models from ZIKV infections. Therefore, the intrinsic limitation of subunit vaccines can be overcome through shielding these artificially exposed unfavorable epitopes. The engineered EDIII vaccine generated in this study is a promising vaccine candidate that can be further developed to battle ZIKV infections.",2019 Aug 13,"['Tai, Wanbo', 'Chen, Jiawei', 'Zhao, Guangyu', 'Geng, Qibin', 'He, Lei', 'Chen, Yuehong', 'Zhou, Yusen', 'Li, Fang', 'Du, Lanying']",J Virol,,,True
4867e0d05f067189d610ca8e764d52dcc50a7b49,PMC,"The alpha-1 subunit of the Na(+),K(+)-ATPase (ATP1A1) is required for macropinocytic entry of respiratory syncytial virus (RSV) in human respiratory epithelial cells",http://dx.doi.org/10.1371/journal.ppat.1007963,PMC6695199,31381610,CC0,"Human respiratory syncytial virus (RSV) is the leading viral cause of acute pediatric lower respiratory tract infections worldwide, with no available vaccine or effective antiviral drug. To gain insight into virus-host interactions, we performed a genome-wide siRNA screen. The expression of over 20,000 cellular genes was individually knocked down in human airway epithelial A549 cells, followed by infection with RSV expressing green fluorescent protein (GFP). Knockdown of expression of the cellular ATP1A1 protein, which is the major subunit of the Na(+),K(+)-ATPase of the plasma membrane, had one of the strongest inhibitory effects on GFP expression and viral titer. Inhibition was not observed for vesicular stomatitis virus, indicating that it was RSV-specific rather than a general effect. ATP1A1 formed clusters in the plasma membrane very early following RSV infection, which was independent of replication but dependent on the attachment glycoprotein G. RSV also triggered activation of ATP1A1, resulting in signaling by c-Src-kinase activity that transactivated epidermal growth factor receptor (EGFR) by Tyr845 phosphorylation. ATP1A1 signaling and activation of both c-Src and EGFR were found to be required for efficient RSV uptake. Signaling events downstream of EGFR culminated in the formation of macropinosomes. There was extensive uptake of RSV virions into macropinosomes at the beginning of infection, suggesting that this is a major route of RSV uptake, with fusion presumably occurring in the macropinosomes rather than at the plasma membrane. Important findings were validated in primary human small airway epithelial cells (HSAEC). In A549 cells and HSAEC, RSV uptake could be inhibited by the cardiotonic steroid ouabain and the digitoxigenin derivative PST2238 (rostafuroxin) that bind specifically to the ATP1A1 extracellular domain and block RSV-triggered EGFR Tyr845 phosphorylation. In conclusion, we identified ATP1A1 as a host protein essential for macropinocytic entry of RSV into respiratory epithelial cells, and identified PST2238 as a potential anti-RSV drug.",2019 Aug 5,"['Lingemann, Matthias', 'McCarty, Thomas', 'Liu, Xueqiao', 'Buchholz, Ursula J.', 'Surman, Sonja', 'Martin, Scott E.', 'Collins, Peter L.', 'Munir, Shirin']",PLoS Pathog,,,True
4fbfedadab204c5165514312dd7cba7a907aaaba,PMC,"Projections of epidemic transmission and estimation of vaccination impact during an ongoing Ebola virus disease outbreak in Northeastern Democratic Republic of Congo, as of Feb. 25, 2019",http://dx.doi.org/10.1371/journal.pntd.0007512,PMC6695208,31381606,CC BY,"BACKGROUND: As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak. METHODS: For short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott’s rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts. RESULTS: During validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone. CONCLUSIONS: Our projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges.",2019 Aug 5,"['Worden, Lee', 'Wannier, Rae', 'Hoff, Nicole A.', 'Musene, Kamy', 'Selo, Bernice', 'Mossoko, Mathias', 'Okitolonda-Wemakoy, Emile', 'Muyembe Tamfum, Jean Jacques', 'Rutherford, George W.', 'Lietman, Thomas M.', 'Rimoin, Anne W.', 'Porco, Travis C.', 'Kelly, J. Daniel']",PLoS Negl Trop Dis,,,True
65e9f8a82b109e83a69346c1504bb80951337584,PMC,"Projections of epidemic transmission and estimation of vaccination impact during an ongoing Ebola virus disease outbreak in Northeastern Democratic Republic of Congo, as of Feb. 25, 2019",http://dx.doi.org/10.1371/journal.pntd.0007512,PMC6695208,31381606,CC BY,"BACKGROUND: As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak. METHODS: For short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott’s rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts. RESULTS: During validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone. CONCLUSIONS: Our projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges.",2019 Aug 5,"['Worden, Lee', 'Wannier, Rae', 'Hoff, Nicole A.', 'Musene, Kamy', 'Selo, Bernice', 'Mossoko, Mathias', 'Okitolonda-Wemakoy, Emile', 'Muyembe Tamfum, Jean Jacques', 'Rutherford, George W.', 'Lietman, Thomas M.', 'Rimoin, Anne W.', 'Porco, Travis C.', 'Kelly, J. Daniel']",PLoS Negl Trop Dis,,,False
e8735adff7db8b800e72ed1e036597d7f8da892f,PMC,"Projections of epidemic transmission and estimation of vaccination impact during an ongoing Ebola virus disease outbreak in Northeastern Democratic Republic of Congo, as of Feb. 25, 2019",http://dx.doi.org/10.1371/journal.pntd.0007512,PMC6695208,31381606,CC BY,"BACKGROUND: As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak. METHODS: For short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott’s rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts. RESULTS: During validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone. CONCLUSIONS: Our projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges.",2019 Aug 5,"['Worden, Lee', 'Wannier, Rae', 'Hoff, Nicole A.', 'Musene, Kamy', 'Selo, Bernice', 'Mossoko, Mathias', 'Okitolonda-Wemakoy, Emile', 'Muyembe Tamfum, Jean Jacques', 'Rutherford, George W.', 'Lietman, Thomas M.', 'Rimoin, Anne W.', 'Porco, Travis C.', 'Kelly, J. Daniel']",PLoS Negl Trop Dis,,,False
d5e3c682efc3533dacc214a3b1aae252574002f9,PMC,"Projections of epidemic transmission and estimation of vaccination impact during an ongoing Ebola virus disease outbreak in Northeastern Democratic Republic of Congo, as of Feb. 25, 2019",http://dx.doi.org/10.1371/journal.pntd.0007512,PMC6695208,31381606,CC BY,"BACKGROUND: As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak. METHODS: For short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott’s rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts. RESULTS: During validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone. CONCLUSIONS: Our projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges.",2019 Aug 5,"['Worden, Lee', 'Wannier, Rae', 'Hoff, Nicole A.', 'Musene, Kamy', 'Selo, Bernice', 'Mossoko, Mathias', 'Okitolonda-Wemakoy, Emile', 'Muyembe Tamfum, Jean Jacques', 'Rutherford, George W.', 'Lietman, Thomas M.', 'Rimoin, Anne W.', 'Porco, Travis C.', 'Kelly, J. Daniel']",PLoS Negl Trop Dis,,,False
65b5ab5e4a75ded33fb4303b5ac146b0f777504f,PMC,"Projections of epidemic transmission and estimation of vaccination impact during an ongoing Ebola virus disease outbreak in Northeastern Democratic Republic of Congo, as of Feb. 25, 2019",http://dx.doi.org/10.1371/journal.pntd.0007512,PMC6695208,31381606,CC BY,"BACKGROUND: As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak. METHODS: For short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott’s rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts. RESULTS: During validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone. CONCLUSIONS: Our projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges.",2019 Aug 5,"['Worden, Lee', 'Wannier, Rae', 'Hoff, Nicole A.', 'Musene, Kamy', 'Selo, Bernice', 'Mossoko, Mathias', 'Okitolonda-Wemakoy, Emile', 'Muyembe Tamfum, Jean Jacques', 'Rutherford, George W.', 'Lietman, Thomas M.', 'Rimoin, Anne W.', 'Porco, Travis C.', 'Kelly, J. Daniel']",PLoS Negl Trop Dis,,,False
80fb9bce892b4c067d947718ef4acbb7a97b6b30,PMC,"Projections of epidemic transmission and estimation of vaccination impact during an ongoing Ebola virus disease outbreak in Northeastern Democratic Republic of Congo, as of Feb. 25, 2019",http://dx.doi.org/10.1371/journal.pntd.0007512,PMC6695208,31381606,CC BY,"BACKGROUND: As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak. METHODS: For short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott’s rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts. RESULTS: During validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone. CONCLUSIONS: Our projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges.",2019 Aug 5,"['Worden, Lee', 'Wannier, Rae', 'Hoff, Nicole A.', 'Musene, Kamy', 'Selo, Bernice', 'Mossoko, Mathias', 'Okitolonda-Wemakoy, Emile', 'Muyembe Tamfum, Jean Jacques', 'Rutherford, George W.', 'Lietman, Thomas M.', 'Rimoin, Anne W.', 'Porco, Travis C.', 'Kelly, J. Daniel']",PLoS Negl Trop Dis,,,False
effd69b43d00d16da6ccbbca34093c5511a23c1a,PMC,"Projections of epidemic transmission and estimation of vaccination impact during an ongoing Ebola virus disease outbreak in Northeastern Democratic Republic of Congo, as of Feb. 25, 2019",http://dx.doi.org/10.1371/journal.pntd.0007512,PMC6695208,31381606,CC BY,"BACKGROUND: As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak. METHODS: For short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott’s rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts. RESULTS: During validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone. CONCLUSIONS: Our projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges.",2019 Aug 5,"['Worden, Lee', 'Wannier, Rae', 'Hoff, Nicole A.', 'Musene, Kamy', 'Selo, Bernice', 'Mossoko, Mathias', 'Okitolonda-Wemakoy, Emile', 'Muyembe Tamfum, Jean Jacques', 'Rutherford, George W.', 'Lietman, Thomas M.', 'Rimoin, Anne W.', 'Porco, Travis C.', 'Kelly, J. Daniel']",PLoS Negl Trop Dis,,,False
0998f467d6ad9a98bb3a9ad7b0f268466693569f,PMC,"Projections of epidemic transmission and estimation of vaccination impact during an ongoing Ebola virus disease outbreak in Northeastern Democratic Republic of Congo, as of Feb. 25, 2019",http://dx.doi.org/10.1371/journal.pntd.0007512,PMC6695208,31381606,CC BY,"BACKGROUND: As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak. METHODS: For short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott’s rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts. RESULTS: During validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone. CONCLUSIONS: Our projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges.",2019 Aug 5,"['Worden, Lee', 'Wannier, Rae', 'Hoff, Nicole A.', 'Musene, Kamy', 'Selo, Bernice', 'Mossoko, Mathias', 'Okitolonda-Wemakoy, Emile', 'Muyembe Tamfum, Jean Jacques', 'Rutherford, George W.', 'Lietman, Thomas M.', 'Rimoin, Anne W.', 'Porco, Travis C.', 'Kelly, J. Daniel']",PLoS Negl Trop Dis,,,False
12b72571a55281637fd01760fe7f29575ebf20be,PMC,"Projections of epidemic transmission and estimation of vaccination impact during an ongoing Ebola virus disease outbreak in Northeastern Democratic Republic of Congo, as of Feb. 25, 2019",http://dx.doi.org/10.1371/journal.pntd.0007512,PMC6695208,31381606,CC BY,"BACKGROUND: As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak. METHODS: For short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott’s rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts. RESULTS: During validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone. CONCLUSIONS: Our projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges.",2019 Aug 5,"['Worden, Lee', 'Wannier, Rae', 'Hoff, Nicole A.', 'Musene, Kamy', 'Selo, Bernice', 'Mossoko, Mathias', 'Okitolonda-Wemakoy, Emile', 'Muyembe Tamfum, Jean Jacques', 'Rutherford, George W.', 'Lietman, Thomas M.', 'Rimoin, Anne W.', 'Porco, Travis C.', 'Kelly, J. Daniel']",PLoS Negl Trop Dis,,,False
cf7f5f1fd4ffa74de5215f4c546d2253aa6f4bbd,PMC,"Projections of epidemic transmission and estimation of vaccination impact during an ongoing Ebola virus disease outbreak in Northeastern Democratic Republic of Congo, as of Feb. 25, 2019",http://dx.doi.org/10.1371/journal.pntd.0007512,PMC6695208,31381606,CC BY,"BACKGROUND: As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak. METHODS: For short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott’s rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts. RESULTS: During validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone. CONCLUSIONS: Our projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges.",2019 Aug 5,"['Worden, Lee', 'Wannier, Rae', 'Hoff, Nicole A.', 'Musene, Kamy', 'Selo, Bernice', 'Mossoko, Mathias', 'Okitolonda-Wemakoy, Emile', 'Muyembe Tamfum, Jean Jacques', 'Rutherford, George W.', 'Lietman, Thomas M.', 'Rimoin, Anne W.', 'Porco, Travis C.', 'Kelly, J. Daniel']",PLoS Negl Trop Dis,,,False
3adfcb05fa2004182d3c232a69429d2b1adfe12f,PMC,Synthesis and Application of Silver Nanoparticles (Ag NPs) for the Prevention of Infection in Healthcare Workers,http://dx.doi.org/10.3390/ijms20153620,PMC6695748,31344881,CC BY,"Silver is easily available and is known to have microbicidal effect; moreover, it does not impose any adverse effects on the human body. The microbicidal effect is mainly due to silver ions, which have a wide antibacterial spectrum. Furthermore, the development of multidrug-resistant bacteria, as in the case of antibiotics, is less likely. Silver ions bind to halide ions, such as chloride, and precipitate; therefore, when used directly, their microbicidal activity is shortened. To overcome this issue, silver nanoparticles (Ag NPs) have been recently synthesized and frequently used as microbicidal agents that release silver ions from particle surface. Depending on the specific surface area of the nanoparticles, silver ions are released with high efficiency. In addition to their bactericidal activity, small Ag NPs (<10 nm in diameter) affect viruses although the microbicidal effect of silver mass is weak. Because of their characteristics, Ag NPs are useful countermeasures against infectious diseases, which constitute a major issue in the medical field. Thus, medical tools coated with Ag NPs are being developed. This review outlines the synthesis and utilization of Ag NPs in the medical field, focusing on environment-friendly synthesis and the suppression of infections in healthcare workers (HCWs).",2019 Jul 24,"['Nakamura, Shingo', 'Sato, Masahiro', 'Sato, Yoko', 'Ando, Naoko', 'Takayama, Tomohiro', 'Fujita, Masanori', 'Ishihara, Masayuki']",Int J Mol Sci,,,True
f9f0d3495e6f8f04b60c9e1cf9a3cf1423d51cc7,PMC,"Enhanced surveillance for severe pneumonia, Thailand 2010–2015",http://dx.doi.org/10.1186/s12889-019-6774-5,PMC6696659,,CC BY,"BACKGROUND: The etiology of severe pneumonia is frequently not identified by routine disease surveillance in Thailand. Since 2010, the Thailand Ministry of Public Health (MOPH) and US CDC have conducted surveillance to detect known and new etiologies of severe pneumonia. METHODS: Surveillance for severe community-acquired pneumonia was initiated in December 2010 among 30 hospitals in 17 provinces covering all regions of Thailand. Interlinked clinical, laboratory, pathological and epidemiological components of the network were created with specialized guidelines for each to aid case investigation and notification. Severe pneumonia was defined as chest-radiograph confirmed pneumonia of unknown etiology in a patient hospitalized ≤48 h and requiring intubation with ventilator support or who died within 48 h after hospitalization; patients with underlying chronic pulmonary or neurological disease were excluded. Respiratory and pathological specimens were tested by reverse transcription polymerase chain reaction for nine viruses, including Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and 14 bacteria. Cases were reported via a secure web-based system. RESULTS: Of specimens from 972 cases available for testing during December 2010 through December 2015, 589 (60.6%) had a potential etiology identified; 399 (67.8%) were from children aged < 5 years. At least one viral agent was detected in 394 (40.5%) cases, with the most common of single vial pathogen detected being respiratory syncytial virus (RSV) (110/589, 18.7%) especially in children under 5 years. Bacterial pathogens were detected in 341 cases of which 67 cases had apparent mixed infections. The system added MERS-CoV testing in September 2012 as part of Thailand’s outbreak preparedness; no cases were identified from the 767 samples tested. CONCLUSIONS: Enhanced surveillance improved the understanding of the etiology of severe pneumonia cases and improved the MOPH’s preparedness and response capacity for emerging respiratory pathogens in Thailand thereby enhanced global health security. Guidelines for investigation of severe pneumonia from this project were incorporated into surveillance and research activities within Thailand and shared for adaption by other countries.",2019 May 10,"['Bunthi, Charatdao', 'Baggett, Henry C.', 'Gregory, Christopher J.', 'Thamthitiwat, Somsak', 'Yingyong, Thitipong', 'Paveenkittiporn, Wantana', 'Kerdsin, Anusak', 'Chittaganpitch, Malinee', 'Ruangchira-urai, Ruchira', 'Akarasewi, Pasakorn', 'Ungchusak, Kumnuan']",BMC Public Health,,,True
edca7aed5e25c0b8888f93a5f78ce0a1b27ed1d7,PMC,Successes and challenges of the One Health approach in Kenya over the last decade,http://dx.doi.org/10.1186/s12889-019-6772-7,PMC6696663,,CC BY,"More than 75% of emerging infectious diseases are zoonotic in origin and a transdisciplinary, multi-sectoral One Health approach is a key strategy for their effective prevention and control. In 2004, US Centers for Disease Control and Prevention office in Kenya (CDC Kenya) established the Global Disease Detection Division of which one core component was to support, with other partners, the One Health approach to public health science. After catalytic events such as the global expansion of highly pathogenic H5N1 and the 2006 East African multi-country outbreaks of Rift Valley Fever, CDC Kenya supported key Kenya government institutions including the Ministry of Health and the Ministry of Agriculture, Livestock, and Fisheries to establish a framework for multi-sectoral collaboration at national and county level and a coordination office referred to as the Zoonotic Disease Unit (ZDU). The ZDU has provided Kenya with an institutional framework to highlight the public health importance of endemic and epidemic zoonoses including RVF, rabies, brucellosis, Middle East Respiratory Syndrome Coronavirus, anthrax and other emerging issues such as anti-microbial resistance through capacity building programs, surveillance, workforce development, research, coordinated investigation and outbreak response. This has led to improved outbreak response, and generated data (including discovery of new pathogens) that has informed disease control programs to reduce burden of and enhance preparedness for endemic and epidemic zoonotic diseases, thereby enhancing global health security. Since 2014, the Global Health Security Agenda implemented through CDC Kenya and other partners in the country has provided additional impetus to maintain this effort and Kenya’s achievement now serves as a model for other countries in the region. Significant gaps remain in implementation of the One Health approach at subnational administrative levels; there are sustainability concerns, competing priorities and funding deficiencies.",2019 May 10,"['Munyua, Peninah M.', 'Njenga, M. Kariuki', 'Osoro, Eric M.', 'Onyango, Clayton O.', 'Bitek, Austine O.', 'Mwatondo, Athman', 'Muturi, Mathew K.', 'Musee, Norah', 'Bigogo, Godfrey', 'Otiang, Elkanah', 'Ade, Fredrick', 'Lowther, Sara A.', 'Breiman, Robert F.', 'Neatherlin, John', 'Montgomery, Joel', 'Widdowson, Marc-Alain']",BMC Public Health,,,True
8befdc2bb43130a5e90c11061e8bc8955718a825,PMC,Progress in public health risk communication in China: lessons learned from SARS to H7N9,http://dx.doi.org/10.1186/s12889-019-6778-1,PMC6696672,,CC BY,"BACKGROUND: Following the SARS outbreak, the World Health Organization revised the International Health Regulations to include risk communication as one of the core capacity areas. In 2006, the U.S. Centers for Disease Control and Prevention’s Global Disease Detection [GDD] program began collaborating with China to enhance China’s risk communication capacity to address gaps in the SARS communication response. This article describes tangible improvements in China’s public health emergency risk communication capacity between the SARS and H7N9 outbreaks; documents U.S. CDC GDD cooperative technical assistance during 2006–2017; and shares lessons learnt to benefit other countries and contribute to enhance global health security. METHOD: A questionnaire based on the WHO Joint External Evaluation tool [Risk Communication section] was developed. A key communications official from the China National Health Commission [NHC] completed the questionnaire retrospectively to reflect China’s capacity to manage communication response before, during and after the outbreaks of SARS in 2003, influenza H1N1 in 2009, and influenza H7N9 in 2013. A literature search was also conducted in English and Chinese to further substantiate the results of the questionnaire completed by NHC. RESULTS: China demonstrated significantly improved risk communication capacities of pre-event, during event and post event responses to H7N9 when compared to the SARS response. China NHC improved its response through preparedness, availability of dedicated staff and resources for risk communication, internal clearance mechanisms, standard operating procedures with national response parties external to NHC, rumor management, communication with international agencies and consistent messaging with healthcare and private sectors. Correspondingly, the perceived level of trust that the public had in the NHC following outbreaks rose between the SARS and H7N9 response. CONCLUSION: Risk communication capacities in China have increased during the ten years between the SARS outbreak of 2003 and the H7N9 outbreak of 2013. Long-term risk communication capacity building efforts in bilateral collaborations are uncommon. The U.S. CDC GDD project was one of the first such collaborations worldwide. The lessons learned from this project may benefit lower and middle-income countries as they build their national emergency risk communication capacity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-019-6778-1) contains supplementary material, which is available to authorized users.",2019 May 10,"['Frost, Melinda', 'Li, Richun', 'Moolenaar, Ronald', 'Mao, Qun’an', 'Xie, Ruiqian']",BMC Public Health,,,True
191480bd880b13cbec0b421f7689e7d3f0fdc120,PMC,Building laboratory capacity to detect and characterize pathogens of public and global health security concern in Kenya,http://dx.doi.org/10.1186/s12889-019-6770-9,PMC6696698,,CC BY,"Since 1979, multiple CDC Kenya programs have supported the development of diagnostic expertise and laboratory capacity in Kenya. In 2004, CDC’s Global Disease Detection (GDD) program within the Division of Global Health Protection in Kenya (DGHP-Kenya) initiated close collaboration with Kenya Medical Research Institute (KEMRI) and developed a laboratory partnership called the Diagnostic and Laboratory Systems Program (DLSP). DLSP built onto previous efforts by malaria, human immunodeficiency virus (HIV) and tuberculosis (TB) programs and supported the expansion of the diagnostic expertise and capacity in KEMRI and the Ministry of Health. First, DLSP developed laboratory capacity for surveillance of diarrheal, respiratory, zoonotic and febrile illnesses to understand the etiology burden of these common illnesses and support evidenced-based decisions on vaccine introductions and recommendations in Kenya. Second, we have evaluated and implemented new diagnostic technologies such as TaqMan Array Cards (TAC) to detect emerging or reemerging pathogens and have recently added a next generation sequencer (NGS). Third, DLSP provided rapid laboratory diagnostic support for outbreak investigation to Kenya and regional countries. Fourth, DLSP has been assisting the Kenya National Public Health laboratory-National Influenza Center and microbiology reference laboratory to obtain World Health Organization (WHO) certification and ISO15189 accreditation respectively. Fifth, we have supported biosafety and biosecurity curriculum development to help Kenyan laboratories safely and appropriately manage infectious pathogens. These achievements, highlight how in collaboration with existing CDC programs working on HIV, tuberculosis and malaria, the Global Health Security Agenda can have significantly improve public health in Kenya and the region. Moreover, Kenya provides an example as to how laboratory science can help countries detect and control of infectious disease outbreaks and other public health threats more rapidly, thus enhancing global health security.",2019 May 10,"['Hunsperger, Elizabeth', 'Juma, Bonventure', 'Onyango, Clayton', 'Ochieng, John B.', 'Omballa, Victor', 'Fields, Barry S.', 'Njenga, M. Kariuki', 'Mwangi, Jane', 'Bigogo, Godfrey', 'Omore, Richard', 'Otieno, Nancy', 'Chaves, Sandra S.', 'Munyua, Peninah', 'Njau, Daniel Macharia', 'Verani, Jennifer', 'Lowther, Sara', 'Breiman, Robert F.', 'Montgomery, Joel M', 'De Cock, Kevin M.', 'Widdowson, Marc-Alain', None]",BMC Public Health,,,True
97ccb371dde90e32d62250fa0a00cacc8b67066e,PMC,Ten years of global disease detection and counting: program accomplishments and lessons learned in building global health security,http://dx.doi.org/10.1186/s12889-019-6769-2,PMC6696700,,CC BY,,2019 May 10,"['Montgomery, Joel M.', 'Woolverton, Abbey', 'Hedges, Sarah', 'Pitts, Dana', 'Alexander, Jessica', 'Ijaz, Kashef', 'Angulo, Fred', 'Dowell, Scott', 'Katz, Rebecca', 'Henao, Olga']",BMC Public Health,,,True
298d325e27d8cafcd150d56a199a5ce099ee2b07,PMC,"A ten-year China-US laboratory collaboration: improving response to influenza threats in China and the world, 2004–2014",http://dx.doi.org/10.1186/s12889-019-6776-3,PMC6696701,,CC BY,"The emergence of severe acute respiratory syndrome (SARS) underscored the importance of influenza detection and response in China. From 2004, the Chinese National Influenza Center (CNIC) and the United States Centers for Disease Control and Prevention (USCDC) initiated Cooperative Agreements to build capacity in influenza surveillance in China. From 2004 to 2014, CNIC and USCDC collaborated on the following activities: 1) developing human technical expertise in virology and epidemiology in China; 2) developing a comprehensive influenza surveillance system by enhancing influenza-like illness (ILI) reporting and virological characterization; 3) strengthening analysis, utilization and dissemination of surveillance data; and 4) improving early response to influenza viruses with pandemic potential. Since 2004, CNIC expanded its national influenza surveillance and response system which, as of 2014, included 408 laboratories and 554 sentinel hospitals. With support from USCDC, more than 2500 public health staff from China received virology and epidemiology training, enabling > 98% network laboratories to establish virus isolation and/or nucleic acid detection techniques. CNIC established viral drug resistance surveillance and platforms for gene sequencing, reverse genetics, serologic detection, and vaccine strains development. CNIC also built a bioinformatics platform to strengthen data analysis and utilization, publishing weekly on-line influenza surveillance reports in English and Chinese. The surveillance system collects 200,000–400,000 specimens and tests more than 20,000 influenza viruses annually, which provides valuable information for World Health Organization (WHO) influenza vaccine strain recommendations. In 2010, CNIC became the sixth WHO Collaborating Centre for Influenza. CNIC has strengthened virus and data sharing, and has provided training and reagents for other countries to improve global capacity for influenza control and prevention. The collaboration’s successes were built upon shared mission and values, emphasis on long-term capacity development and sustainability, and leadership commitment.",2019 May 10,"['Shu, Yuelong', 'Song, Ying', 'Wang, Dayan', 'Greene, Carolyn M.', 'Moen, Ann', 'Lee, C. K.', 'Chen, Yongkun', 'Xu, Xiyan', 'McFarland, Jeffrey', 'Xin, Li', 'Bresee, Joseph', 'Zhou, Suizan', 'Chen, Tao', 'Zhang, Ran', 'Cox, Nancy']",BMC Public Health,,,True
c32c30f41c1f50f242b977297a8ff85eda1a2987,PMC,The Antiviral and Antitumor Effects of Defective Interfering Particles/Genomes and Their Mechanisms,http://dx.doi.org/10.3389/fmicb.2019.01852,PMC6696905,31447826,CC BY,"Defective interfering particles (DIPs), derived naturally from viral particles, are not able to replicate on their own. Several studies indicate that DIPs exert antiviral effects via multiple mechanisms. DIPs are able to activate immune responses and suppress virus replication cycles, such as competing for viral replication products, impeding the packaging, release and invasion of viruses. Other studies show that DIPs can be used as a vaccine against viral infection. Moreover, DIPs/DI genomes display antitumor effects by inducing tumor cell apoptosis and promoting dendritic cell maturation. With genetic modified techniques, it is possible to improve its safety against both viruses and tumors. In this review, a comprehensive discussion on the effects exerted by DIPs is provided. We further highlight the clinical significance of DIPs and propose that DIPs can open up a new platform for antiviral and antitumor therapies.",2019 Aug 9,"['Yang, Yicheng', 'Lyu, Taibiao', 'Zhou, Runing', 'He, Xiaoen', 'Ye, Kaiyan', 'Xie, Qian', 'Zhu, Li', 'Chen, Tingting', 'Shen, Chu', 'Wu, Qinghua', 'Zhang, Bao', 'Zhao, Wei']",Front Microbiol,,,True
abf6a328e40c6c5c193e5f1be38d808c3ce18ef0,PMC,Prevalence and complete genome of bovine norovirus with novel VP1 genotype in calves in China,http://dx.doi.org/10.1038/s41598-019-48569-4,PMC6700072,31427703,CC BY,"Bovine norovirus (BNoV) is a diarrhea-causing pathogen of calves. In this study, 211 diarrheic fecal samples were collected from 25 farms across six provinces in China, between November 2017 and September 2018. 20.4% of the samples were detected as BNoV-positive by RT-PCR. Phylogenetic analyses based on RdRp, VP1, and VP2 fragments revealed these BNoV strains had unique evolutionary characteristics. The complete genome of strain Bo/BET–17/18/CH was successfully sequenced. It was 7321 nucleotides (nt) in length, shared 79.4–80.9% nt identity with all five BNoV genomes, clustered on a separate branch of the phylogenetic tree, suggesting that strain Bo/BET–17/18/CH could represent a novel BNoV strain. Two interesting characteristics were found in the genome: (i) the VP1 sequence differed greatly from known BNoV VP1 sequences; (ii) a recombination event is predicted within the ORF1–ORF2 overlap. Moreover 16.3% (7/43) of the BNoV were identified as the novel VP1 genotype, which were distributed on four farms across two provinces, indicating that the novel VP1 genotype strain has spread. To our knowledge, this is first description of the molecular and genomic characteristics of BNoV in China. These findings extend our understanding of the genetic evolution and epidemics of BNoV.",2019 Aug 19,"['Wang, Yuelin', 'Yue, Hua', 'Tang, Cheng']",Sci Rep,,,False
033460fbe61491f8505732ee22a5cb3387f3e4a3,PMC,Prevalence and complete genome of bovine norovirus with novel VP1 genotype in calves in China,http://dx.doi.org/10.1038/s41598-019-48569-4,PMC6700072,31427703,CC BY,"Bovine norovirus (BNoV) is a diarrhea-causing pathogen of calves. In this study, 211 diarrheic fecal samples were collected from 25 farms across six provinces in China, between November 2017 and September 2018. 20.4% of the samples were detected as BNoV-positive by RT-PCR. Phylogenetic analyses based on RdRp, VP1, and VP2 fragments revealed these BNoV strains had unique evolutionary characteristics. The complete genome of strain Bo/BET–17/18/CH was successfully sequenced. It was 7321 nucleotides (nt) in length, shared 79.4–80.9% nt identity with all five BNoV genomes, clustered on a separate branch of the phylogenetic tree, suggesting that strain Bo/BET–17/18/CH could represent a novel BNoV strain. Two interesting characteristics were found in the genome: (i) the VP1 sequence differed greatly from known BNoV VP1 sequences; (ii) a recombination event is predicted within the ORF1–ORF2 overlap. Moreover 16.3% (7/43) of the BNoV were identified as the novel VP1 genotype, which were distributed on four farms across two provinces, indicating that the novel VP1 genotype strain has spread. To our knowledge, this is first description of the molecular and genomic characteristics of BNoV in China. These findings extend our understanding of the genetic evolution and epidemics of BNoV.",2019 Aug 19,"['Wang, Yuelin', 'Yue, Hua', 'Tang, Cheng']",Sci Rep,,,True
dc819c2ad69ad256a76b84efdf56063bc398fad5,PMC,Evaluation of antigenic differences between wild and Sabin vaccine strains of poliovirus using the pseudovirus neutralization test,http://dx.doi.org/10.1038/s41598-019-48534-1,PMC6700111,31427704,CC BY,"In the endgame of global polio eradication, serosurveillance is essential to monitor each country’s vulnerability to poliomyelitis outbreaks. Previously, we developed pseudovirus poliovirus (PV) neutralization test (pPNT) with type 1, 2, and 3 PV pseudovirus (PV(pv)), which possess a luciferase-encoding PV replicon in the capsids of wild-type strains (PV(pv)[WT]), showing that pPNT with type 2 and 3 PV(pv)(WT) but not type 1 shows high correlation with the conventional PV neutralization test (cPNT) performed with vaccine strains. Here, we analyse the antigenicity of PV(pv)(WT) and PV(pv) with capsid proteins of Sabin vaccine strains (PV(pv)[Sabin]) in human serum. Type 2 and 3 PV(pv)(WT) and PV(pv)(Sabin) show similar antigenicity in the analysed set of human sera in contrast to type 1 PV(pv). The levels of PV(pv)(Sabin) infection (%), including about 70% of PV(pv) infection (%) measured in the presence of human serum diluted to the cPNT titre, serve as the optimal threshold values for pPNT (5% for type 1 and 2, 10% for type 3) to show high correlation with cPNT results. Our results suggest that pPNT with PV(pv)(Sabin) could serve as an alternative to cPNT and provide a rationale for pPNT threshold values.",2019 Aug 19,"['Arita, Minetaro', 'Iwai-Itamochi, Masae']",Sci Rep,,,True
8b478a28315d64c252456c44fe8ead59d389f615,PMC,Crystal Structure of Refolding Fusion Core of Lassa Virus GP2 and Design of Lassa Virus Fusion Inhibitors,http://dx.doi.org/10.3389/fmicb.2019.01829,PMC6700223,31456769,CC BY,"The envelope glycoproteins GP1 and GP2 of Lassa virus (LASV) bind to the host cell receptors to mediate viral infection. So far, no approved vaccines and specific treatment options against LASV exist. To develop specific fusion inhibitors against LASV, we solved the crystal structure of the post-fusion 6 helix bundle (6-HB) formed by two heptad repeat domains (HR1 and HR2) of GP2. This fusion core contains a parallel trimeric coiled-coil of three HR1 helices, around which three HR2 helices are entwined in an antiparallel manner. Various hydrophobic and charged interactions form between HR1 and HR2 domains to stabilize the overall conformation of GP2 fusion core. Based on the structure, we designed several peptides spanning the HR2 domain and tested their antiviral activities. We found that the longer HR2 peptides were effective in inhibiting LASV GPC protein-mediated cell–cell fusion under low pH condition. These results not only suggest that LASV infects the target cell mainly through endocytosis, including micropinocytosis, and membrane fusion at low pH, but also provide an important basis for rational design of LASV fusion inhibitors.",2019 Aug 13,"['Zhang, Xuejiao', 'Wang, Cong', 'Chen, Baohua', 'Wang, Qian', 'Xu, Wei', 'Ye, Sheng', 'Jiang, Shibo', 'Zhu, Yun', 'Zhang, Rongguang']",Front Microbiol,,,True
14b876ff3e2540832646c2c9b8be67354fa93991,PMC,Phylogenetic evidence of a novel lineage of canine pneumovirus and a naturally recombinant strain isolated from dogs with respiratory illness in Thailand,http://dx.doi.org/10.1186/s12917-019-2035-1,PMC6700830,31426794,CC BY,"BACKGROUND: Canine pneumovirus (CPV) is a pathogen that causes respiratory disease in dogs, and recent outbreaks in shelters in America and Europe have been reported. However, based on published data and documents, the identification of CPV and its variant in clinically symptomatic individual dogs in Thailand through Asia is limited. Therefore, the aims of this study were to determine the emergence of CPV and to consequently establish the genetic characterization and phylogenetic analysis of the CPV strains from 209 dogs showing respiratory distress in Thailand. RESULTS: This study identified and described the full-length CPV genome from three strains, designated herein as CPV_CP13 TH/2015, CPV_CP82 TH/2016 and CPV_SR1 TH/2016, that were isolated from six dogs out of 209 dogs (2.9%) with respiratory illness in Thailand. Phylogenetic analysis suggested that these three Thai CPV strains (CPV TH strains) belong to the CPV subgroup A and form a novel lineage; proposed as the Asian prototype. Specific mutations in the deduced amino acids of these CPV TH strains were found in the G/glycoprotein sequence, suggesting potential substitution sites for subtype classification. Results of intragenic recombination analysis revealed that CPV_CP82 TH/2016 is a recombinant strain, where the recombination event occurred in the L gene with the Italian prototype CPV Bari/100–12 as the putative major parent. Selective pressure analysis demonstrated that the majority of the nucleotides in the G/glycoprotein were under purifying selection with evidence of positive selection sites. CONCLUSIONS: This collective information on the CPV TH strains is the first evidence of CPV emergence with genetic characterization in Thailand and as first report in Asia, where homologous recombination acts as a potential force driving the genetic diversity and shaping the evolution of canine pneumovirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-019-2035-1) contains supplementary material, which is available to authorized users.",2019 Aug 19,"['Piewbang, Chutchai', 'Techangamsuwan, Somporn']",BMC Vet Res,,,False
223d9fa8ef42ff808b3301ec2f96cb0a13bf059e,PMC,Phylogenetic evidence of a novel lineage of canine pneumovirus and a naturally recombinant strain isolated from dogs with respiratory illness in Thailand,http://dx.doi.org/10.1186/s12917-019-2035-1,PMC6700830,31426794,CC BY,"BACKGROUND: Canine pneumovirus (CPV) is a pathogen that causes respiratory disease in dogs, and recent outbreaks in shelters in America and Europe have been reported. However, based on published data and documents, the identification of CPV and its variant in clinically symptomatic individual dogs in Thailand through Asia is limited. Therefore, the aims of this study were to determine the emergence of CPV and to consequently establish the genetic characterization and phylogenetic analysis of the CPV strains from 209 dogs showing respiratory distress in Thailand. RESULTS: This study identified and described the full-length CPV genome from three strains, designated herein as CPV_CP13 TH/2015, CPV_CP82 TH/2016 and CPV_SR1 TH/2016, that were isolated from six dogs out of 209 dogs (2.9%) with respiratory illness in Thailand. Phylogenetic analysis suggested that these three Thai CPV strains (CPV TH strains) belong to the CPV subgroup A and form a novel lineage; proposed as the Asian prototype. Specific mutations in the deduced amino acids of these CPV TH strains were found in the G/glycoprotein sequence, suggesting potential substitution sites for subtype classification. Results of intragenic recombination analysis revealed that CPV_CP82 TH/2016 is a recombinant strain, where the recombination event occurred in the L gene with the Italian prototype CPV Bari/100–12 as the putative major parent. Selective pressure analysis demonstrated that the majority of the nucleotides in the G/glycoprotein were under purifying selection with evidence of positive selection sites. CONCLUSIONS: This collective information on the CPV TH strains is the first evidence of CPV emergence with genetic characterization in Thailand and as first report in Asia, where homologous recombination acts as a potential force driving the genetic diversity and shaping the evolution of canine pneumovirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-019-2035-1) contains supplementary material, which is available to authorized users.",2019 Aug 19,"['Piewbang, Chutchai', 'Techangamsuwan, Somporn']",BMC Vet Res,,,True
66ffa4cc6c425005054eea58142f7b23307025ef,PMC,The altered gut virome community in rhesus monkeys is correlated with the gut bacterial microbiome and associated metabolites,http://dx.doi.org/10.1186/s12985-019-1211-z,PMC6700990,31426820,CC BY,"BACKGROUND: The gut microbiome is closely associated with the health of the host; although the interaction between the bacterial microbiome and the whole virome has rarely been studied, it is likely of medical importance. Examination of the interactions between the gut bacterial microbiome and virome of rhesus monkey would significantly contribute to revealing the gut microbiome composition. METHODS: Here, we conducted a metagenomic analysis of the gut microbiome of rhesus monkeys in a longitudinal cohort treated with an antibiotic cocktail, and we documented the interactions between the bacterial microbiome and virome. The depletion of viral populations was confirmed at the species level by real-time PCR. We also detected changes in the gut metabolome by GC-MS and LC-MS. RESULTS: A majority of bacteria were depleted after treatment with antibiotics, and the Shannon diversity index decreased from 2.95 to 0.22. Furthermore, the abundance-based coverage estimator (ACE) decreased from 104.47 to 33.84, and the abundance of eukaryotic viruses also changed substantially. In the annotation, 6 families of DNA viruses and 1 bacteriophage family were present in the normal monkeys but absent after gut bacterial microbiome depletion. Intriguingly, we discovered that changes in the gut bacterial microbiome composition may promote changes in the gut virome composition, and tryptophan, arginine, and quinone may play roles in the interaction between the bacterial microbiome and virome. CONCLUSION: Our results indicated that the clearly altered composition of the virome was correlated with depletion in the bacterial community and that metabolites produced by bacteria possibly play important roles in the interaction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-019-1211-z) contains supplementary material, which is available to authorized users.",2019 Aug 19,"['Li, Heng', 'Li, Hongzhe', 'Wang, Jingjing', 'Guo, Lei', 'Fan, Haitao', 'Zheng, Huiwen', 'Yang, Zening', 'Huang, Xing', 'Chu, Manman', 'Yang, Fengmei', 'He, Zhanlong', 'Li, Nan', 'Yang, Jinxi', 'Wu, Qiongwen', 'Shi, Haijing', 'Liu, Longding']",Virol J,,,True
6fecfe80a5c76339823ebe9f93f69eb8388cc882,PMC,"Comparison of viral and epidemiological profiles of hospitalized children with severe acute respiratory infection in Beijing and Shanghai, China",http://dx.doi.org/10.1186/s12879-019-4385-5,PMC6701130,31429710,CC BY,"BACKGROUND: No comparison data have been reported on viral and epidemiological profiles of hospitalized children with severe acute respiratory infection (SARI) in Beijing or Shanghai, China. METHODS: We collected 700 nasopharyngeal aspirates (NPA) from hospitalized children with SARI in Beijing (northern China) and Shanghai (southern China). Multiple respiratory viruses (including 15 common viruses) were screened by validated polymerase chain reaction (PCR) or real-time reverse transcription-PCR assays and confirmed by sequencing. Demographic data and the distribution of viral infections were also examined. RESULTS: Of 700 samples, 547 (78.1%) tested positive for viral infections. The picornaviruses (PIC), which included rhinovirus (RV) and enterovirus (EV), were the most common (34.0%), followed by respiratory syncytial virus (RSV) (28.3%), human bocavirus (HBoV) (19.1%), adenovirus (ADV) (13.7%), human coronaviruses (HCoV) (10.7%), influenza A and B (8.9%), parainfluenza virus (PIV 1–3) (7.9%), and human metapneumovirus (HMPV) (5.0%). PIC (RV/EV) and RSV were the most prevalent etiological agents of SARI in both cities. The total and age-matched prevalence of RSV, HCoV, and hMPV among SARI children under 5 years old were significantly higher in Beijing than in Shanghai. Different age and seasonal distribution patterns of the viral infections were found between Beijing and Shanghai. CONCLUSIONS: Viral infection was tested and shown to be the most prevalent etiological agent among children with SARI in either the Beijing or the Shanghai area, while showing different patterns of viral and epidemiological profiles. Our findings provide a better understanding of the roles of geographic location and climate in respiratory viral infections in hospitalized children with SARI.",2019 Aug 20,"['Zhao, Yanjie', 'Lu, Roujian', 'Shen, Jun', 'Xie, Zhengde', 'Liu, Gaoshan', 'Tan, Wenjie']",BMC Infect Dis,,,True
08d0057eaad519e3d6ef88ffbbc2187b2c11f126,PMC,Genetic and biological characterisation of Zika virus isolates from different Brazilian regions,http://dx.doi.org/10.1590/0074-02760190150,PMC6701881,31432892,CC BY,"BACKGROUND: Zika virus (ZIKV) infections reported in recent epidemics have been linked to clinical complications that had never been associated with ZIKV before. Adaptive mutations could have contributed to the successful emergence of ZIKV as a global health threat to a nonimmune population. However, the causal relationships between the ZIKV genetic determinants, the pathogenesis and the rapid spread in Latin America and in the Caribbean remain widely unknown. OBJECTIVES: The aim of this study was to characterise three ZIKV isolates obtained from patient samples during the 2015/2016 Brazilian epidemics. METHODS: The ZIKV genomes of these strains were completely sequenced and in vitro infection kinetics experiments were carried out in cell lines and human primary cells. FINDINGS: Eight nonsynonymous substitutions throughout the viral genome of the three Brazilian isolates were identified. Infection kinetics experiments were carried out with mammalian cell lines A549, Huh7.5, Vero E6 and human monocyte-derived dendritic cells (mdDCs) and insect cells (Aag2, C6/36 and AP61) and suggest that some of these mutations might be associated with distinct viral fitness. The clinical isolates also presented differences in their infectivity rates when compared to the well-established ZIKV strains (MR766 and PE243), especially in their abilities to infect mammalian cells. MAIN CONCLUSIONS: Genomic analysis of three recent ZIKV isolates revealed some nonsynonymous substitutions, which could have an impact on the viral fitness in mammalian and insect cells.",2019 Aug 19,"['Strottmann, Daisy Maria', 'Zanluca, Camila', 'Mosimann, Ana Luiza Pamplona', 'Koishi, Andrea C', 'Auwerter, Nathalia Cavalheiro', 'Faoro, Helisson', 'Cataneo, Allan Henrique Depieri', 'Kuczera, Diogo', 'Wowk, Pryscilla Fanini', 'Bordignon, Juliano', 'Duarte dos Santos, Claudia Nunes']",Mem Inst Oswaldo Cruz,,,True
bdfca78549a3a21e5774810537a3eaa0390b8e59,PMC,Genetic and biological characterisation of Zika virus isolates from different Brazilian regions,http://dx.doi.org/10.1590/0074-02760190150,PMC6701881,31432892,CC BY,"BACKGROUND: Zika virus (ZIKV) infections reported in recent epidemics have been linked to clinical complications that had never been associated with ZIKV before. Adaptive mutations could have contributed to the successful emergence of ZIKV as a global health threat to a nonimmune population. However, the causal relationships between the ZIKV genetic determinants, the pathogenesis and the rapid spread in Latin America and in the Caribbean remain widely unknown. OBJECTIVES: The aim of this study was to characterise three ZIKV isolates obtained from patient samples during the 2015/2016 Brazilian epidemics. METHODS: The ZIKV genomes of these strains were completely sequenced and in vitro infection kinetics experiments were carried out in cell lines and human primary cells. FINDINGS: Eight nonsynonymous substitutions throughout the viral genome of the three Brazilian isolates were identified. Infection kinetics experiments were carried out with mammalian cell lines A549, Huh7.5, Vero E6 and human monocyte-derived dendritic cells (mdDCs) and insect cells (Aag2, C6/36 and AP61) and suggest that some of these mutations might be associated with distinct viral fitness. The clinical isolates also presented differences in their infectivity rates when compared to the well-established ZIKV strains (MR766 and PE243), especially in their abilities to infect mammalian cells. MAIN CONCLUSIONS: Genomic analysis of three recent ZIKV isolates revealed some nonsynonymous substitutions, which could have an impact on the viral fitness in mammalian and insect cells.",2019 Aug 19,"['Strottmann, Daisy Maria', 'Zanluca, Camila', 'Mosimann, Ana Luiza Pamplona', 'Koishi, Andrea C', 'Auwerter, Nathalia Cavalheiro', 'Faoro, Helisson', 'Cataneo, Allan Henrique Depieri', 'Kuczera, Diogo', 'Wowk, Pryscilla Fanini', 'Bordignon, Juliano', 'Duarte dos Santos, Claudia Nunes']",Mem Inst Oswaldo Cruz,,,False
4ce9221ee5f89f2bf3f24b25a42b81f64ec81657,PMC,"Molecular detection of viruses in Kenyan bats and discovery of novel astroviruses, caliciviruses and rotaviruses",http://dx.doi.org/10.1007/s12250-016-3930-2,PMC6702250,28393313,CC BY,"This is the first country-wide surveillance of bat-borne viruses in Kenya spanning from 2012–2015 covering sites perceived to have medium to high level bat-human interaction. The objective of this surveillance study was to apply a non-invasive approach using fresh feces to detect viruses circulating within the diverse species of Kenyan bats. We screened for both DNA and RNA viruses; specifically, astroviruses (AstVs), adenoviruses (ADVs), caliciviruses (CalVs), coronaviruses (CoVs), flaviviruses, filoviruses, paramyxoviruses (PMVs), polyomaviruses (PYVs) and rotaviruses. We used family-specific primers, amplicon sequencing and further characterization by phylogenetic analysis. Except for filoviruses, eight virus families were detected with varying distributions and positive rates across the five regions (former provinces) studied. AstVs (12.83%), CoVs (3.97%), PMV (2.4%), ADV (2.26%), PYV (1.65%), CalVs (0.29%), rotavirus (0.19%) and flavivirus (0.19%). Novel CalVs were detected in Rousettus aegyptiacus and Mops condylurus while novel Rotavirus-A-related viruses were detected in Taphozous bats and R. aegyptiacus. The two Rotavirus A (RVA) strains detected were highly related to human strains with VP6 genotypes I2 and I16. Genotype I16 has previously been assigned to human RVA-strain B10 from Kenya only, which raises public health concern, particularly considering increased human-bat interaction. Additionally, 229E-like bat CoVs were detected in samples originating from Hipposideros bats roosting in sites with high human activity. Our findings confirm the presence of diverse viruses in Kenyan bats while providing extended knowledge on bat virus distribution. The detection of viruses highly related to human strains and hence of public health concern, underscores the importance of continuous surveillance. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s12250-016-3930-2 and is accessible for authorized users.",2017 Apr 6,"['Waruhiu, Cecilia', 'Ommeh, Sheila', 'Obanda, Vincent', 'Agwanda, Bernard', 'Gakuya, Francis', 'Ge, Xing-Yi', 'Yang, Xing-Lou', 'Wu, Li-Jun', 'Zohaib, Ali', 'Hu, Ben', 'Shi, Zheng-Li']",Virol Sin,,,False
ccc8cfc07dd790364ca7968e3e057dbdff53c792,PMC,"Molecular detection of viruses in Kenyan bats and discovery of novel astroviruses, caliciviruses and rotaviruses",http://dx.doi.org/10.1007/s12250-016-3930-2,PMC6702250,28393313,CC BY,"This is the first country-wide surveillance of bat-borne viruses in Kenya spanning from 2012–2015 covering sites perceived to have medium to high level bat-human interaction. The objective of this surveillance study was to apply a non-invasive approach using fresh feces to detect viruses circulating within the diverse species of Kenyan bats. We screened for both DNA and RNA viruses; specifically, astroviruses (AstVs), adenoviruses (ADVs), caliciviruses (CalVs), coronaviruses (CoVs), flaviviruses, filoviruses, paramyxoviruses (PMVs), polyomaviruses (PYVs) and rotaviruses. We used family-specific primers, amplicon sequencing and further characterization by phylogenetic analysis. Except for filoviruses, eight virus families were detected with varying distributions and positive rates across the five regions (former provinces) studied. AstVs (12.83%), CoVs (3.97%), PMV (2.4%), ADV (2.26%), PYV (1.65%), CalVs (0.29%), rotavirus (0.19%) and flavivirus (0.19%). Novel CalVs were detected in Rousettus aegyptiacus and Mops condylurus while novel Rotavirus-A-related viruses were detected in Taphozous bats and R. aegyptiacus. The two Rotavirus A (RVA) strains detected were highly related to human strains with VP6 genotypes I2 and I16. Genotype I16 has previously been assigned to human RVA-strain B10 from Kenya only, which raises public health concern, particularly considering increased human-bat interaction. Additionally, 229E-like bat CoVs were detected in samples originating from Hipposideros bats roosting in sites with high human activity. Our findings confirm the presence of diverse viruses in Kenyan bats while providing extended knowledge on bat virus distribution. The detection of viruses highly related to human strains and hence of public health concern, underscores the importance of continuous surveillance. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s12250-016-3930-2 and is accessible for authorized users.",2017 Apr 6,"['Waruhiu, Cecilia', 'Ommeh, Sheila', 'Obanda, Vincent', 'Agwanda, Bernard', 'Gakuya, Francis', 'Ge, Xing-Yi', 'Yang, Xing-Lou', 'Wu, Li-Jun', 'Zohaib, Ali', 'Hu, Ben', 'Shi, Zheng-Li']",Virol Sin,,,True
02c4e304d5e063e9bd66d293a8c1472a5865c173,PMC,Identification of Diverse Bat Alphacoronaviruses and Betacoronaviruses in China Provides New Insights Into the Evolution and Origin of Coronavirus-Related Diseases,http://dx.doi.org/10.3389/fmicb.2019.01900,PMC6702311,31474969,CC BY,"Outbreaks of severe acute respiratory syndrome (SARS) in 2002, Middle East respiratory syndrome in 2012 and fatal swine acute diarrhea syndrome in 2017 caused serious infectious diseases in humans and in livestock, resulting in serious public health threats and huge economic losses. All such coronaviruses (CoVs) were confirmed to originate from bats. To continuously monitor the epidemic-related CoVs in bats, virome analysis was used to classify CoVs from 831 bats of 15 species in Yunnan, Guangxi, and Sichuan Provinces between August 2016 and May 2017. We identified 11 CoV strains from 22 individual samples of four bat species. Identification of four alpha-CoVs from Scotophilus kuhlii in Guangxi, which was closely related to a previously reported bat CoV and porcine epidemic diarrhea virus (PEDV), revealed a bat-swine lineage under the genus Alphacoronavirus. A recombinant CoV showed that the PEDV probably originated from the CoV of S. kuhlii. Another alpha-CoV, α-YN2018, from Rhinolophus affinis in Yunnan, suggested that this alpha-CoV lineage had multiple host origins, and α-YN2018 had recombined with CoVs of other bat species over time. We identified five SARS-related CoVs (SARSr-CoVs) in Rhinolophus bats from Sichuan and Yunnan and confirmed that angiotensin-converting enzyme 2 usable SARSr-CoVs were continuously circulating in Rhinolophus spp. in Yunnan. The other beta-CoV, strain β-GX2018, found in Cynopterus sphinx of Guangxi, represented an independently evolved lineage different from known CoVs of Rousettus and Eonycteris bats. The identification of diverse CoVs here provides new genetic data for understanding the distribution and source of pathogenic CoVs in China.",2019 Aug 14,"['Han, Yelin', 'Du, Jiang', 'Su, Haoxiang', 'Zhang, Junpeng', 'Zhu, Guangjian', 'Zhang, Shuyi', 'Wu, Zhiqiang', 'Jin, Qi']",Front Microbiol,,,True
e0ec066b46e51073a3ccfbc05fe626d0c93f8b29,PMC,"Seroprevalence and risk factor associated with respiratory viral pathogens in dual-purpose cattle of Aguachica, Rio de Oro, and La Gloria municipalities in Cesar department, Colombia",http://dx.doi.org/10.14202/vetworld.2019.951-958,PMC6702553,31528017,CC BY,"AIM: The research was conducted to determine the seroprevalence and risk factor associated with respiratory viral pathogens in dual-purpose cattle of Aguachica, Rio de Oro and La Gloria municipalities in Cesar department, Colombia. MATERIALS AND METHODS: The seroprevalence study was done from the random sampling (n=1000) of blood collected from 29 dual-purpose herds, located in three municipalities (Aguachica, Rio de Oro, and La Gloria) of Cesar department. The presence of antibodies against bovine herpesvirus type 1 (BHV-1), bovine respiratory syncytial virus (BRSV), bovine viral diarrhea virus (BVDV), and bovine parainfluenza-3 virus (BPI-3V) in the samples was detected by indirect enzyme-linked immunosorbent assay. Epidemiological data were obtained using a questionnaire administered to the owner or manager of each herd. RESULTS: The overall highest seroprevalence was observed for BHV-1 (94.7%), followed by BRSV (98.6%), BVDV (35.2%), and BPI-3V (47.1%). Regarding the seroprevalence by municipalities, there was a statistical association (p<0.05) for BVDV; however, for BRSV, BHV-1, and BPI-3V, no statistical association was found (p>0.05) between seropositive values and the municipalities, indicating that animal was seropositive in similar proportions in the three municipalities. Female sex and older animals (>24 months) were a significant risk factor for BHV-1 and BPI-3V infection. Regarding the clinical signs, there was a statistical association (p<0.05) between the seropositive values of BVDV and most of clinical signs observed, except for abortion. CONCLUSION: This research confirms the high seroprevalence of the respiratory viral pathogens in nonvaccinated cattle within the study areas. Therefore, appropriate sanitary management practices and routine vaccination programs should be adopted to reduce the seroprevalence of these infectious agents.",2019 Jul 4,"['León, Juan Carlos Pinilla', 'Diaz, Wilson', 'Vasquez, María Cristina', 'Tobón, Julio Cesar', 'Sánchez, Alfredo', 'Ortiz, Diego']",Vet World,,,True
ebc2ff4fdabfafc1ceb338e54aa4d11240efeef9,PMC,"Protective effect of intranasal peste des petits ruminants virus and bacterin vaccinations: Clinical, hematological, serological, and serum oxidative stress changes in challenged goats",http://dx.doi.org/10.14202/vetworld.2019.945-950,PMC6702579,31528016,CC BY,"BACKGROUND AND AIM: The current vaccination for peste des petits ruminants virus (PPRV) is stalled by myriad challenges and continuous endemicity of pneumonia due to fulminant bacterial complication in goats. The present study evaluated the protective effect of intranasal PPRV linage 1 and bacterine vaccinations. MATERIALS AND METHODS: Twelve West African Dwarf (WAD) goats aged 6 months were randomly grouped and vaccinated within 2 weeks using a combination of PPRV lineage 1 vaccine (Nig/75), and bacterin from Mannheimia haemolytica (Mh) or Pasteurella multocida intranasally. The goats were observed for 3 weeks post-vaccination before comingled with a known infected WAD goat with apparent clinical signs of peste des petits ruminants and further observed clinically for 5 weeks post-infection (PI). Blood samples were taken for hematology while sera were assayed for antioxidants (glutathione peroxidase, glutathione transferase, and superoxide dismutase) activities and pro-oxidants (malondialdehyde content, reduced glutathione, hydrogen peroxide generation(,) and myeloperoxidase) using spectrophotometric methods. Data were subjected to parametric statistics at α=0.05 using GraphPad Prism version 21. RESULTS: Clinically, there were pyrexia, oculonasal discharge, diarrhea, anemia, leukopenia, and increased pro-oxidants in the unvaccinated goats, while moderate neutrophilia and leukocytosis were observed in PPRV and bacterin vaccinated goats. Two unvaccinated goats were weak and euthanized at 13 and 28 days PI. The goats vaccinated with PPRV and Mh showed better response clinically and biochemically. CONCLUSION: The mucosal vaccination of goats with PPRV vaccine and bacterine will protect against exposure and culminate in the development of protective mucosal, humoral, and cell-mediated immune responses. This vaccination strategy will provide framework needed in the prevention and control of endemic caprine pneumonia in Nigeria.",2019 Jul 3,"['Jarikre, Theophilus Aghogho', 'Taiwo, Jeremiah Olalekan', 'Emikpe, Benjamin Obukowho', 'Akpavie, Stephen Owarioro']",Vet World,,,True
71d2ad06792c5adb2c8fb934e9bedc53659b1dfe,PMC,"Immune-complex glomerulonephritis in cats: a retrospective study based on clinico-pathological data, histopathology and ultrastructural features",http://dx.doi.org/10.1186/s12917-019-2046-y,PMC6702729,31429743,CC BY,"BACKGROUND: Chronic kidney disease (CKD) has typically a non-immune mediated origin in cats and immune-complex glomerulonephritis (ICGN) is scarcely described. Aims of this study were to characterize ICGN by light and electron microscopy and identify associations with clinico-pathological findings. In addition, comparisons between cats with ICGN and non immune-complex glomerulonephritis (non-ICGN) were performed. Renal samples examined between 2010 and 2019 were considered if both light and electron microscopy were performed. Signalment, feline immunodeficiency virus (FIV) and leukemia virus (FeLV) status, serum creatinine concentration, urine protein-to-creatinine (UPC) ratio, systolic blood pressure (SBP) and International Renal Interest Society (IRIS) stage were retrieved and used for comparisons. RESULTS: Sixty-eight client-owned cats were included. Thirty-seven cats (54.4%) had ICGN and 31 (45.6%) non-ICGN. Eighteen (48.6%) with ICGN had membranous glomerulonephropathy (MGN), 14 (37.8%) membranoproliferative glomerulonephritis (MPGN), and 5 (13.5%) mesangioproliferative glomerulonephritis (MeGN). Clinico-pathological data were not associated with any type of ICGN. Among cats with non-ICGN, 11 (35.5%) had end-stage CKD, 9 (29%) focal segmental glomerulosclerosis, 6 (19.4%) global and multifocal mesangiosclerosis, 2 (6.5%) glomerular atrophy, 2 (6.5%) renal dysplasia and 1 (3.1%) amyloidosis. Eight (25.8%) cats with non-ICGN had chronic interstitial nephritis (CIN) grade 1, 13 (41.9%) grade 2 and 10 (32.3%) grade 3; creatinine and UPC ratio increased with CIN grades (p = 0.001, p < 0.001). Cats with ICGN were more frequently FIV or FeLV-infected (OR:11.4; 95%CI:1.4–94.4; p = 0.024), had higher UPC ratio (OR:6.8; 95%CI:2.5–18.2; p < 0.001) and were younger (OR:0.9; 95%CI:0.7–1.0; p = 0.042) than cats with non-ICGN. CONCLUSIONS: MGN and MPGN were the most common morphological diagnoses of ICGN in cats. Unfortunately, none of the investigated findings differentiated ICGN morphological diagnoses. Serum creatinine concentration and UPC ratio were directly associated with grades of CIN (p = 0.001 and p < 0.001, respectively), confirming previous literature. More ICGN than non-ICGN was observed in cats with retroviral infections, younger cats and higher UPC ratio.",2019 Aug 20,"['Rossi, Francesco', 'Aresu, Luca', 'Martini, Valeria', 'Trez, Davide', 'Zanetti, Rossella', 'Coppola, Luigi Michele', 'Ferri, Filippo', 'Zini, Eric']",BMC Vet Res,,,True
43f3b3e2af86af484ab7aae55ad9b2354e4a14eb,PMC,The Common Missed Handwashing Instances and Areas after 15 Years of Hand-Hygiene Education,http://dx.doi.org/10.1155/2019/5928924,PMC6702815,31485238,CC BY,"The outbreak of severe acute respiratory syndrome (SARS) claimed the lives of 286 Hong Kong people in 2003. Since then, the Hong Kong government has been promoting the benefits of proper hand hygiene. There are few studies that explore the general quality of handwashing and the hand-hygiene practices of the public of Hong Kong; given this, the aim of this study is to explore this neglected topic. This study is a quantitative study that was conducted in January 2018. The results show that the majority of participants only wash their hands after using the toilet (87%) or handling vomitus or faecal matter (91%). The mean duration of handwashing was 36.54 seconds (SD = 18.57). The areas of the hand most neglected during handwashing were the fingertips (48.1%), medial area (30.5%), and back of the hand (28%). A multiple logistic regression shows that participants who have reached third-level education or higher often tend to be more hand hygienic than those who have not reached third-level education (p ≤ 0.001, B = 1.003). Thus, participants aged 30 and above tend to neglect 5 more areas of the hand than those aged below 30 (p=0.001, B = 4.933).",2019 Aug 8,"['Wong, J. S. W.', 'Lee, J. K. F.']",J Environ Public Health,,,True
c95771649886404cfec24c5c139e851c614e632b,PMC,A novel sub-epidemic modeling framework for short-term forecasting epidemic waves,http://dx.doi.org/10.1186/s12916-019-1406-6,PMC6704534,31438953,CC BY,"BACKGROUND: Simple phenomenological growth models can be useful for estimating transmission parameters and forecasting epidemic trajectories. However, most existing phenomenological growth models only support single-peak outbreak dynamics whereas real epidemics often display more complex transmission trajectories. METHODS: We develop and apply a novel sub-epidemic modeling framework that supports a diversity of epidemic trajectories including stable incidence patterns with sustained or damped oscillations to better understand and forecast epidemic outbreaks. We describe how to forecast an epidemic based on the premise that the observed coarse-scale incidence can be decomposed into overlapping sub-epidemics at finer scales. We evaluate our modeling framework using three outbreak datasets: Severe Acute Respiratory Syndrome (SARS) in Singapore, plague in Madagascar, and the ongoing Ebola outbreak in the Democratic Republic of Congo (DRC) and four performance metrics. RESULTS: The sub-epidemic wave model outperforms simpler growth models in short-term forecasts based on performance metrics that account for the uncertainty of the predictions namely the mean interval score (MIS) and the coverage of the 95% prediction interval. For example, we demonstrate how the sub-epidemic wave model successfully captures the 2-peak pattern of the SARS outbreak in Singapore. Moreover, in short-term sequential forecasts, the sub-epidemic model was able to forecast the second surge in case incidence for this outbreak, which was not possible using the simple growth models. Furthermore, our findings support the view that the national incidence curve of the Ebola epidemic in DRC follows a stable incidence pattern with periodic behavior that can be decomposed into overlapping sub-epidemics. CONCLUSIONS: Our findings highlight how overlapping sub-epidemics can capture complex epidemic dynamics, including oscillatory behavior in the trajectory of the epidemic wave. This observation has significant implications for interpreting apparent noise in incidence data where the oscillations could be dismissed as a result of overdispersion, rather than an intrinsic part of the epidemic dynamics. Unless the oscillations are appropriately modeled, they could also give a false positive, or negative, impression of the impact from public health interventions. These preliminary results using sub-epidemic models can help guide future efforts to better understand the heterogenous spatial and social factors shaping sub-epidemic patterns for other infectious diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12916-019-1406-6) contains supplementary material, which is available to authorized users.",2019 Aug 22,"['Chowell, Gerardo', 'Tariq, Amna', 'Hyman, James M.']",BMC Med,,,True
0de1279a965dab5fd7cdce4862b0f2eab6f20fdd,PMC,Influenza Virus-Induced Robust Expression of SOCS3 Contributes to Excessive Production of IL-6,http://dx.doi.org/10.3389/fimmu.2019.01843,PMC6706793,31474976,CC BY,"Influenza A virus (IAV) remains a major public health threat in the world, as indicated by the severe pneumonia caused by its infection annually. Interleukin-6 (IL-6) involved excessive inflammatory response to IAV infection profoundly contributes to the virus pathogenesis. However, the precise mechanisms underlying such a response are poorly understood. Here we found from both in vivo and in vitro studies that IAV not only induced a surge of IL-6 release, but also greatly upregulated expression of suppressor of cytokine signaling-3 (SOCS3), the potent suppressor of IL-6-associated signal transducer and activator of transcription 3 (STAT3) signaling. Interestingly, there existed a cytokine-independent mechanism of the robust induction of SOCS3 by IAV at early stages of the infection. Furthermore, we employed SOCS3-knockdown transgenic mice (TG), and surprisingly observed from virus challenge experiments using these mice that disruption of SOCS3 expression provided significant protection against IAV infection, as evidenced by attenuated acute lung injury, a higher survival rate of infected animals and lower viral load in infected tissues as compared with those of wild-type littermates under the same condition. The activity of nuclear factor-kappa B (NFκB) and the expression of its target gene IL-6 were suppressed in SOCS3-knockdown A549 cells and the TG mice after infection with IAV. Moreover, we defined that enhanced STAT3 activity caused by SOCS3 silencing was important for the regulation of NFκB and IL-6. These findings establish a critical role for IL-6-STAT3-SOCS3 axis in the pathogenesis of IAV and suggest that influenza virus may have evolved a strategy to circumvent IL-6/STAT3-mediated immune response through upregulating SOCS3.",2019 Aug 16,"['Liu, Shasha', 'Yan, Ruoxiang', 'Chen, Biao', 'Pan, Qidong', 'Chen, Yuhai', 'Hong, Jinxuan', 'Zhang, Lianfeng', 'Liu, Wenjun', 'Wang, Song', 'Chen, Ji-Long']",Front Immunol,,,False
d3669fc36015db30aaecba5e7d608584d9a2cdfa,PMC,Influenza Virus-Induced Robust Expression of SOCS3 Contributes to Excessive Production of IL-6,http://dx.doi.org/10.3389/fimmu.2019.01843,PMC6706793,31474976,CC BY,"Influenza A virus (IAV) remains a major public health threat in the world, as indicated by the severe pneumonia caused by its infection annually. Interleukin-6 (IL-6) involved excessive inflammatory response to IAV infection profoundly contributes to the virus pathogenesis. However, the precise mechanisms underlying such a response are poorly understood. Here we found from both in vivo and in vitro studies that IAV not only induced a surge of IL-6 release, but also greatly upregulated expression of suppressor of cytokine signaling-3 (SOCS3), the potent suppressor of IL-6-associated signal transducer and activator of transcription 3 (STAT3) signaling. Interestingly, there existed a cytokine-independent mechanism of the robust induction of SOCS3 by IAV at early stages of the infection. Furthermore, we employed SOCS3-knockdown transgenic mice (TG), and surprisingly observed from virus challenge experiments using these mice that disruption of SOCS3 expression provided significant protection against IAV infection, as evidenced by attenuated acute lung injury, a higher survival rate of infected animals and lower viral load in infected tissues as compared with those of wild-type littermates under the same condition. The activity of nuclear factor-kappa B (NFκB) and the expression of its target gene IL-6 were suppressed in SOCS3-knockdown A549 cells and the TG mice after infection with IAV. Moreover, we defined that enhanced STAT3 activity caused by SOCS3 silencing was important for the regulation of NFκB and IL-6. These findings establish a critical role for IL-6-STAT3-SOCS3 axis in the pathogenesis of IAV and suggest that influenza virus may have evolved a strategy to circumvent IL-6/STAT3-mediated immune response through upregulating SOCS3.",2019 Aug 16,"['Liu, Shasha', 'Yan, Ruoxiang', 'Chen, Biao', 'Pan, Qidong', 'Chen, Yuhai', 'Hong, Jinxuan', 'Zhang, Lianfeng', 'Liu, Wenjun', 'Wang, Song', 'Chen, Ji-Long']",Front Immunol,,,True
850c8a23db306b9410adc341809d40d8b46635aa,PMC,Development of a real-time loop-mediated isothermal amplification assay for detection of porcine circovirus 3,http://dx.doi.org/10.1186/s12917-019-2037-z,PMC6706899,31443656,CC BY,"BACKGROUND: Porcine circovirus type 3 (PCV3) is an emerging circovirus species, that has been reported in major pig-raising countries including the United States, China, South Korea, Brazil, Spain, and Poland. RESULTS: A real-time loop-mediated isothermal amplification (LAMP) assay was developed for rapid detection of porcine circovirus 3 (PCV3). The method had a detection limit of 1 × 10(1) copies/μL with no cross-reactions with classical swine fever virus (CSFV) C strain, foot-and-mouth disease virus (FMDV), porcine circovirus 2 (PCV2) LG vaccine strain, porcine epidemic diarrhoea virus (PEDV), porcine respiratory and reproductive syndrome virus (PRRSV), or pseudorabies virus (PRV). The PCV3 positive detection rate of 203 clinical samples for the real-time LAMP assay was 89.66% (182/203). CONCLUSIONS: The real-time LAMP assay is highly sensitive, and specific for use in epidemiological investigations of PCV3.",2019 Aug 23,"['Wang, Huanan', 'Liu, Xiangnan', 'Zeng, Fanwen', 'Zhang, Tongyuan', 'Lian, Yuexiao', 'Wu, Miaoli', 'Xiao, Li', 'Zhu, Yujun', 'Zhang, Yu', 'Chen, Meili', 'Huang, Ren', 'Luo, Manlin', 'Cong, Feng', 'Guo, Pengju']",BMC Vet Res,,,True
9702e48b8bce2e6a2e17f0252dbf5c1b0958b9f2,PMC,Critical combination of initial markers for predicting refractory Mycoplasma pneumoniae pneumonia in children: a case control study,http://dx.doi.org/10.1186/s12931-019-1152-5,PMC6706904,31443650,CC BY,"BACKGROUND: It is unclear whether the responses of refractory and common Mycoplasma pneumoniae (MP) pneumonia to macrolides differ. Hence, this study aimed to identify biomarkers that may be used to distinguish refractory and common pneumonias caused by MP in children at hospital admission. METHODS: The study included 123 children divided into five groups according to infection agent and treatment protocol: Group I included those with MP infection without documented viral infection, treated with only macrolides; Group II included those with MP infection without documented viral infection, treated with a combination of macrolides and methylprednisolone; Group III included those with MP infection and documented viral infection, treated with only macrolides; Group IV included those with viral pneumonia without documented MP infection; Group V was the control group composed of admitted children without MP or a documented viral infection. These five groups were further subdivided into Groups A (including Groups I, III, IV, and V) and B (Group II) according to the responses to macrolide treatment. Concentrations of cytokines interleukin 6, interleukin 17, interleukin 18, and tumor necrosis factor-α, and lactate dehydrogenase, and ferritin of all children were evaluated, and these levels were compared among the groups. Statistical comparisons were made using Kruskal Wallis test and Mann-Whitney U test. RESULTS: Serum lactate dehydrogenase, interleukin 18, and ferritin concentrations were significantly higher in Group II than in Groups I, III, IV, and V and were significantly higher in Group B than in Group A. When the serum lactate dehydrogenase concentration was 350 IU/L or higher, the sensitivity and specificity for diagnosing refractory MP pneumonia were 73 and 80%, respectively. When the interleukin 18 level was 360 pg/mL or higher, the sensitivity and specificity for diagnosing refractory MP pneumonia were 93 and 70%, respectively. When the ferritin level was 230 pg/mL or higher, the sensitivity and specificity for diagnosing refractory MP pneumonia were 67 and 67%, respectively. CONCLUSION: These results suggest that serum lactate dehydrogenase, interleukin 18, and ferritin constitute the critical combination of biomarkers useful for predicting refractory MP pneumonia in children at hospital admission.",2019 Aug 23,"['Choi, Young-Jin', 'Jeon, Ju-Hee', 'Oh, Jae-Won']",Respir Res,,,True
efdf0a3bdc300ce80392b2b52be33728db54a51f,PMC,A Novel Gene Underlies Bleomycin-Response Variation in Caenorhabditis elegans,http://dx.doi.org/10.1534/genetics.119.302286,PMC6707474,31171655,CC BY,"Bleomycin is a powerful chemotherapeutic drug used to treat a variety of cancers. However, individual patients vary in their responses to bleomycin. The identification of genetic differences that underlie this response variation could improve treatment outcomes by tailoring bleomycin dosages to each patient. We used the model organism Caenorhabditis elegans to identify genetic determinants of bleomycin-response differences by performing linkage mapping on recombinants derived from a cross between the laboratory strain (N2) and a wild strain (CB4856). This approach identified a small genomic region on chromosome V that underlies bleomycin-response variation. Using near-isogenic lines, and strains with CRISPR-Cas9 mediated deletions and allele replacements, we discovered that a novel nematode-specific gene (scb-1) is required for bleomycin resistance. Although the mechanism by which this gene causes variation in bleomycin responses is unknown, we suggest that a rare variant present in the CB4856 strain might cause differences in the potential stress-response function of scb-1 between the N2 and CB4856 strains, thereby leading to differences in bleomycin resistance.",2019 Aug 6,"['Brady, Shannon C.', 'Zdraljevic, Stefan', 'Bisaga, Karol W.', 'Tanny, Robyn E.', 'Cook, Daniel E.', 'Lee, Daehan', 'Wang, Ye', 'Andersen, Erik C.']",Genetics,,,True
8d40046d4ced2a558530e5e242fabbee66b213d7,PMC,Immuno-modulating properties of Tulathromycin in porcine monocyte-derived macrophages infected with porcine reproductive and respiratory syndrome virus,http://dx.doi.org/10.1371/journal.pone.0221560,PMC6707645,31442273,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-stranded RNA virus that grows in macrophages and causes acute pneumonia in pigs. PRRSV causes devastating losses to the porcine industry. However, due to its high antigenic variability and poorly understood immunopathogenesis, there is currently no effective vaccine or treatment to control PRRSV infection. The common occurrence of PRRSV infection with bacterial infections as well as its inflammatory-driven pathobiology raises the question of the value of antibiotics with immunomodulating properties for the treatment of the disease it causes. The macrolide antibiotic Tulathromycin (TUL) has been found to exhibit potent anti-inflammatory and immunomodulating properties in cattle and pigs. The aim of this study was to characterize the anti-viral and immunomodulating properties of TUL in PRRSV-infected porcine macrophages. Our findings indicate that blood monocyte-derived macrophages are readily infected by PRRSV and can be used as an effective cellular model to study PRRSV pathogenesis. TUL did not change intracellular or extracellular viral titers, not did it alter viral receptors (CD163 and CD169) expression on porcine macrophages. In contrast, TUL exhibited potent immunomodulating properties, which therefore occurred in the absence of any direct antiviral effects against PRRSV. TUL had an additive effect with PRRSV on the induction of macrophage apoptosis, and inhibited virus-induced necrosis. TUL significantly attenuated PRRSV-induced macrophage pro-inflammatory signaling (CXCL-8 and mitochondrial ROS production) and prevented PRRSV inhibition of non-opsonized and opsonized phagocytic function. Together, these data demonstrate that TUL inhibits PRRSV-induced inflammatory responses in porcine macrophages and protects against the phagocytic impairment caused by the virus. Research in live pigs is warranted to assess the potential clinical benefits of this antibiotic in the context of virally induced inflammation and tissue injury.",2019 Aug 23,"['Desmonts de Lamache, D.', 'Moges, R.', 'Siddiq, A.', 'Allain, T.', 'Feener, T. D.', 'Muench, G. P.', 'McKenna, N.', 'Yates, R. M.', 'Buret, A. G.']",PLoS One,,,True
d7788ab137f05cf1c247c60dbe388b80fb5764a7,PMC,STEM: An Open Source Tool for Disease Modeling,http://dx.doi.org/10.1089/hs.2019.0018,PMC6708268,31433284,CC BY,"The Spatiotemporal Epidemiologic Modeler (STEM) is an open source software project supported by the Eclipse Foundation and used by a global community of researchers and public health officials working to track and, when possible, control outbreaks of infectious disease in human and animal populations. STEM is not a model or a tool designed for a specific disease; it is a flexible, modular framework supporting exchange and integration of community models, reusable plug-in components, and denominator data, available to researchers worldwide at www.eclipse.org/stem. A review of multiple projects illustrates its capabilities. STEM has been used to study variations in transmission of seasonal influenza in Israel by strains; evaluate social distancing measures taken to curb the H1N1 epidemic in Mexico City; study measles outbreaks in part of London and inform local policy on immunization; and gain insights into H7N9 avian influenza transmission in China. A multistrain dengue fever model explored the roles of the mosquito vector, cross-strain immunity, and antibody response in the frequency of dengue outbreaks. STEM has also been used to study the impact of variations in climate on malaria incidence. During the Ebola epidemic, a weekly conference call supported the global modeling community; subsequent work modeled the impact of behavioral change and tested disease reintroduction via animal reservoirs. Work in Germany tracked salmonella in pork from farm to fork; and a recent doctoral dissertation used the air travel feature to compare the potential threats posed by weaponizing infectious diseases. Current projects include work in Great Britain to evaluate control strategies for parasitic disease in sheep, and in Germany and Hungary, to validate the model and inform policy decisions for African swine fever. STEM Version 4.0.0, released in early 2019, includes tools used in these projects and updates technical aspects of the framework to ease its use and re-use.",2019 Aug 1,"['Douglas, Judith V.', 'Bianco, Simone', 'Edlund, Stefan', 'Engelhardt, Tekla', 'Filter, Matthias', 'Günther, Taras', 'Hu, Kun (Maggie)', 'Nixon, Emily J.', 'Sevilla, Nereyda L.', 'Swaid, Ahmad', 'Kaufman, James H.']",Health Secur,,,True
bafab6b3dd88dcdefe111698d02f81998c9accdb,PMC,Evolution and containment of transmissible recombinant vector vaccines,http://dx.doi.org/10.1111/eva.12806,PMC6708430,31462917,CC BY,"Transmissible vaccines offer a revolutionary approach for controlling infectious disease and may provide one of the few feasible methods for eliminating pathogens from inaccessible wildlife populations. Current efforts to develop transmissible vaccines use recombinant vector technology whereby pathogen antigens are engineered to be expressed from innocuous infectious viral vectors. The resulting vaccines can transmit from host to host, amplifying the number of vaccine‐protected individuals beyond those initially vaccinated directly through parenteral inoculation. One main engineering challenge is the potential for natural selection to favor vaccine mutants that eliminate or reduce expression of antigenic inserts, resulting in immunogenic decay of the vaccine over time. Here, we study a mathematical model of vector mutation whereby continuous elimination of the antigenic insert results in reversion of the vaccine back into the insert‐free vector. We use this model to quantify the maximum allowable rate of reversion that can be tolerated for a transmissible vaccine to maintain a critical threshold level of immunogenicity against a target pathogen. Our results demonstrate that even for transmissible vaccines where reversion is frequent, performance will often substantially exceed that of conventional, directly administered vaccines. Further, our results demonstrate the feasibility of designing transmissible vaccines that yield desired levels of immunogenicity, yet degrade at a rate sufficient for persistence of the recombinant vaccine within the environment to be minimized.",2019 Jun 12,"['Nuismer, Scott L.', 'Basinski, Andrew', 'Bull, James J.']",Evol Appl,,,True
58bb89f7722922bd9a47cd49e172c498d5cd73cf,PMC,Middle East Respiratory Syndrome Coronavirus and the One Health concept,http://dx.doi.org/10.7717/peerj.7556,PMC6708572,31497405,CC BY,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is one of the major threats to the healthcare systems in some countries, especially in the Arabian Peninsula. MERS-CoV is considered an ideal example of the One Health concept. This is due to the animals, especially dromedary camels, play important roles in the transmission and sustainability of the virus, and the virus can be transmitted through aerosols of infected patients into the environment. However, there is some debate regarding the origin of MERS-CoV either from bats or other unknown reservoirs. The dromedary camel is the only identified animal reservoir to date. These animals play important roles in sustaining the virus in certain communities and may act as an amplifier of the virus by secreting it in their body fluids, especially in nasal and rectal discharges. MERS-CoV has been detected in the nasal and rectal secretions of infected camels, and MERS-CoV of this origin has full capacity to infect human airway epithelium in both in vitro and in vivo models. Other evidence confirms the direct transmission of MERS-CoV from camels to humans, though the role of camel meat and milk products has yet to be well studied. Human-to-human transmission is well documented through contact with an active infected patient or some silently infected persons. Furthermore, there are some significant risk factors of individuals in close contact with a positive MERS-CoV patient, including sleeping in the same patient room, removing patient waste (urine, stool, and sputum), and touching respiratory secretions from the index case. Outbreaks within family clusters have been reported, whereby some blood relative patients were infected through their wives in the same house were not infected. Some predisposing genetic factors favor MERS-CoV infection in some patients, which is worth investigating in the near future. The presence of other comorbidities may be another factor. Overall, there are many unknown/confirmed aspects of the virus/human/animal network. Here, the most recent advances in this context are discussed, and the possible reasons behind the emergence and sustainability of MERS-CoV in certain regions are presented. Identification of the exact mechanism of transmission of MERS-CoV from camels to humans and searching for new reservoir/s are of high priority. This will reduce the shedding of the virus into the environment, and thus the risk of human infection can be mitigated.",2019 Aug 22,"Hemida, Maged Gomaa",PeerJ,,,True
65942c10db7359edef15f156cecccf3deee45b72,PMC,A Competency Framework for Developing Global Laboratory Leaders,http://dx.doi.org/10.3389/fpubh.2019.00199,PMC6710318,31482080,CC BY,"Building sustainable national health laboratory systems requires laboratory leaders who can address complex and changing demands for services and build strong collaborative networks. Global consensus on laboratory leadership competencies is critically important to ensure the harmonization of learning approaches for curriculum development across relevant health sectors. The World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), the World Organisation for Animal Health (OIE), the European Centre for Disease Prevention and Control (ECDC), the U.S. Centers for Disease Control and Prevention (CDC), and the Association of Public Health Laboratories (APHL) have partnered to develop a Laboratory Leadership Competency Framework (CF) that provides a foundation for the Global Laboratory Leadership Programme (GLLP). The CF represents the first global consensus from multiple disciplines on laboratory leadership competencies and provides structure for the development of laboratory leaders with the knowledge, skills and abilities to build bridges, enhance communication, foster collaboration and develop an understanding of existing synergies between the human, animal, environmental, and other relevant health sectors.",2019 Aug 20,"['Albetkova, Adilya', 'Chaignat, Evelyne', 'Gasquet, Philippe', 'Heilmann, Martin', 'Isadore, Jocelyn', 'Jasir, Aftab', 'Martin, Barbara', 'Wilcke, Burton']",Front Public Health,,,True
a11d517c9cdd68c3671429751ed8420fb9fc1485,PMC,Galloyl-Hexahydroxydiphenoyl (HHDP)-Glucose Isolated From Punica granatum L. Leaves Protects Against Lipopolysaccharide (LPS)-Induced Acute Lung Injury in BALB/c Mice,http://dx.doi.org/10.3389/fimmu.2019.01978,PMC6710369,31481965,CC BY,"The hydroalcoholic extract and ethyl acetate fraction of Punica granatum leaves have been known to exhibit anti-inflammatory activities. In this study, we investigated the therapeutic effects of galloyl-hexahydroxydiphenoyl (HHDP)-glucose isolated from pomegranate leaves on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Male BALB/c mice were treated with different doses of galloyl-HHDP-glucose (5, 50, and 100 mg/Kg) or dexamethasone at 5 mg/Kg (per os) 6 h after intra-tracheal instillation of LPS. Vehicle-treated mice were used as controls. Twenty-four hours after LPS challenge, bronchoalveolar lavage fluid (BALF), and lung samples were collected for analyses. They were evaluated by monitoring the expression of NF-κB, JNK, and cytokine genes and proteins, as well as cell migration and lung function. All doses of galloyl-HHDP-glucose inhibited LPS-induced JNK and NF-κB activation. Likewise, the galloyl-HHDP-glucose-treated animals presented reduced expression of the TNF-α, IL-6, and IL-1β genes in the lungs and reduced TNF-α, IL-6, IL-1β, and IL-8 protein levels when compared with the vehicle-treated LPS-challenged mice. In addition, the ALI mice treated with galloyl-HHDP-glucose also presented reduced lung inflammatory cell accumulation, especially that of neutrophils, in their BALF and lungs. In addition, galloyl-HHDP-glucose treatment markedly ameliorated the LPS-induced pulmonary mechanism complications and attenuated weight loss. Overall, we showed for the first time that galloyl-HHDP-glucose protects against ALI, and may be useful for treating ALI and other inflammatory disorders.",2019 Aug 20,"['Pinheiro, Aruanã Joaquim Matheus Costa Rodrigues', 'Mendes, Aleff Ricardo Santos', 'Neves, Milena Dara Farias de Jesus', 'Prado, Carla Máximo', 'Bittencourt-Mernak, Márcia Isabel', 'Santana, Fernanda Paula Roncon', 'Lago, João Henrique G.', 'de Sá, Joicy Cortez', 'da Rocha, Claudia Quintino', 'de Sousa, Eduardo Martins', 'Fontes, Valéria Costa', 'Grisoto, Marco Augusto Gregolin', 'Falcai, Angela', 'Lima-Neto, Lidio Gonçalves']",Front Immunol,,,True
061e49a521b8ea0acbd7c3a61360cc8e0b07e3ca,PMC,Viruses in Vietnamese Patients Presenting with Community-Acquired Sepsis of Unknown Cause,http://dx.doi.org/10.1128/JCM.00386-19,PMC6711913,31217274,CC BY,"Community-acquired (CA) sepsis is a major public health problem worldwide, yet the etiology remains unknown for >50% of the patients. Here we applied metagenomic next-generation sequencing (mNGS) to characterize the human virome in 492 clinical samples (384 sera, 92 pooled nasal and throat swabs, 10 stools, and 6 cerebrospinal fluid samples) from 386 patients (213 adults and 173 children) presenting with CA sepsis who were recruited from 6 hospitals across Vietnam between 2013 and 2015. Specific monoplex PCRs were used subsequently to confirm the presence of viral sequences detected by mNGS. We found sequences related to 47 viral species belonging to 21 families in 358 of 386 (93%) patients, including viruses known to cause human infections. After PCR confirmation, human viruses were found in 52 of 386 patients (13.4%); picornavirus (enteroviruses [n = 14], rhinovirus [n = 5], and parechovirus [n = 2]), hepatitis B virus (n = 10), cytomegalovirus (n = 9), Epstein-Barr virus (n = 5), and rotavirus A (n = 3) were the most common viruses detected. Recently discovered viruses were also found (gemycircularvirus [n = 5] and WU polyomavirus, Saffold virus, salivirus, cyclovirus-VN, and human pegivirus 2 [HPgV2] [n, 1 each]), adding to the growing literature about the geographic distribution of these novel viruses. Notably, sequences related to numerous viruses not previously reported in human tissues were also detected. To summarize, we identified 21 viral species known to be infectious to humans in 52 of 386 (13.4%) patients presenting with CA sepsis of unknown cause. The study, however, cannot directly impute sepsis causation to the viruses identified. The results highlight the fact that it remains a challenge to establish the causative agents in CA sepsis patients, especially in tropical settings such as Vietnam.",2019 Aug 26,"['Anh, Nguyen To', 'Hong, Nguyen Thi Thu', 'Nhu, Le Nguyen Truc', 'Thanh, Tran Tan', 'Lau, Chuen-Yen', 'Limmathurotsakul, Direk', 'Deng, Xutao', 'Rahman, Motiur', 'Chau, Nguyen Van Vinh', 'van Doorn, H. Rogier', 'Thwaites, Guy', 'Delwart, Eric', 'Tan, Le Van']",J Clin Microbiol,,,True
b8a836a0c73faa4072e986d99664f892cef7a579,PMC,Viruses in Vietnamese Patients Presenting with Community-Acquired Sepsis of Unknown Cause,http://dx.doi.org/10.1128/JCM.00386-19,PMC6711913,31217274,CC BY,"Community-acquired (CA) sepsis is a major public health problem worldwide, yet the etiology remains unknown for >50% of the patients. Here we applied metagenomic next-generation sequencing (mNGS) to characterize the human virome in 492 clinical samples (384 sera, 92 pooled nasal and throat swabs, 10 stools, and 6 cerebrospinal fluid samples) from 386 patients (213 adults and 173 children) presenting with CA sepsis who were recruited from 6 hospitals across Vietnam between 2013 and 2015. Specific monoplex PCRs were used subsequently to confirm the presence of viral sequences detected by mNGS. We found sequences related to 47 viral species belonging to 21 families in 358 of 386 (93%) patients, including viruses known to cause human infections. After PCR confirmation, human viruses were found in 52 of 386 patients (13.4%); picornavirus (enteroviruses [n = 14], rhinovirus [n = 5], and parechovirus [n = 2]), hepatitis B virus (n = 10), cytomegalovirus (n = 9), Epstein-Barr virus (n = 5), and rotavirus A (n = 3) were the most common viruses detected. Recently discovered viruses were also found (gemycircularvirus [n = 5] and WU polyomavirus, Saffold virus, salivirus, cyclovirus-VN, and human pegivirus 2 [HPgV2] [n, 1 each]), adding to the growing literature about the geographic distribution of these novel viruses. Notably, sequences related to numerous viruses not previously reported in human tissues were also detected. To summarize, we identified 21 viral species known to be infectious to humans in 52 of 386 (13.4%) patients presenting with CA sepsis of unknown cause. The study, however, cannot directly impute sepsis causation to the viruses identified. The results highlight the fact that it remains a challenge to establish the causative agents in CA sepsis patients, especially in tropical settings such as Vietnam.",2019 Aug 26,"['Anh, Nguyen To', 'Hong, Nguyen Thi Thu', 'Nhu, Le Nguyen Truc', 'Thanh, Tran Tan', 'Lau, Chuen-Yen', 'Limmathurotsakul, Direk', 'Deng, Xutao', 'Rahman, Motiur', 'Chau, Nguyen Van Vinh', 'van Doorn, H. Rogier', 'Thwaites, Guy', 'Delwart, Eric', 'Tan, Le Van']",J Clin Microbiol,,,True
1e9929bbb08fb46de40a699d0c2d2aa7c287e5b4,PMC,Molecular Subtyping of Human Rhinovirus in Children from Three Sub-Saharan African Countries,http://dx.doi.org/10.1128/JCM.00723-19,PMC6711929,31270180,CC BY,"The pathogenesis of human rhinovirus (HRV) during severe respiratory disease remains undefined; thus, we aimed to explore the relationship between the HRV molecular subtyping results obtained during severe and asymptomatic childhood infections. Nasopharyngeal/oropharyngeal swabs from children (1 to 59 months of age) hospitalized with pneumonia and from age-frequency-matched controls were collected between August 2011 and August 2013. Swabs were tested for respiratory pathogens, including HRV, using quantitative real-time PCR assays. HRV-positive samples were sequenced for phylogenetic analysis by targeting the 5′ noncoding region (5′NCR). Our data showed that there were no differences in the prevalence of HRV detection among cases and controls (21% versus 20%, P = 0.693); however, among children 13 to 59 months old, HRV detection was more often case associated (21% versus 16%; P = 0.009), with the results mainly driven by HRV-C (12% versus 7%; P = 0.001). Overall, there were no differences in the results of molecular subtyping of the HRV species prevalence among cases (for HRV-A, 48%; for HRV-B, 7%; for HRV-C, 45%) and controls (for HRV-A, 45%; for HRV-B, 10%; for HRV-C, 45% [P = 0.496]). Those with pneumonia and HRV-C were older (12.1 versus 9.4 months, P = 0.033) and more likely to present with wheeze (35% versus 25%, P = 0.031) than those with HRV-A cases. Thus, the rate of HRV detection was high, with similar degrees of genetic diversity among cases and controls, confounding the interpretation of the presence of HRV in nasopharyngeal samples for attribution of a causal role in the pathogenesis of severe pneumonia in infants. However, among children 13 to 59 months of age, HRV detection, in particular, HRV-C detection, was associated with case status, especially among children with wheezing disease.",2019 Aug 26,"['Baillie, Vicky L.', 'Moore, David P.', 'Mathunjwa, Azwifarwi', 'Morailane, Palesa', 'Simões, Eric A. F.', 'Madhi, Shabir A.']",J Clin Microbiol,,,True
f456d52312c2f0250444202a1a002fb126be2338,PMC,Molecular Subtyping of Human Rhinovirus in Children from Three Sub-Saharan African Countries,http://dx.doi.org/10.1128/JCM.00723-19,PMC6711929,31270180,CC BY,"The pathogenesis of human rhinovirus (HRV) during severe respiratory disease remains undefined; thus, we aimed to explore the relationship between the HRV molecular subtyping results obtained during severe and asymptomatic childhood infections. Nasopharyngeal/oropharyngeal swabs from children (1 to 59 months of age) hospitalized with pneumonia and from age-frequency-matched controls were collected between August 2011 and August 2013. Swabs were tested for respiratory pathogens, including HRV, using quantitative real-time PCR assays. HRV-positive samples were sequenced for phylogenetic analysis by targeting the 5′ noncoding region (5′NCR). Our data showed that there were no differences in the prevalence of HRV detection among cases and controls (21% versus 20%, P = 0.693); however, among children 13 to 59 months old, HRV detection was more often case associated (21% versus 16%; P = 0.009), with the results mainly driven by HRV-C (12% versus 7%; P = 0.001). Overall, there were no differences in the results of molecular subtyping of the HRV species prevalence among cases (for HRV-A, 48%; for HRV-B, 7%; for HRV-C, 45%) and controls (for HRV-A, 45%; for HRV-B, 10%; for HRV-C, 45% [P = 0.496]). Those with pneumonia and HRV-C were older (12.1 versus 9.4 months, P = 0.033) and more likely to present with wheeze (35% versus 25%, P = 0.031) than those with HRV-A cases. Thus, the rate of HRV detection was high, with similar degrees of genetic diversity among cases and controls, confounding the interpretation of the presence of HRV in nasopharyngeal samples for attribution of a causal role in the pathogenesis of severe pneumonia in infants. However, among children 13 to 59 months of age, HRV detection, in particular, HRV-C detection, was associated with case status, especially among children with wheezing disease.",2019 Aug 26,"['Baillie, Vicky L.', 'Moore, David P.', 'Mathunjwa, Azwifarwi', 'Morailane, Palesa', 'Simões, Eric A. F.', 'Madhi, Shabir A.']",J Clin Microbiol,,,False
1963419be00172f1a626b5a45b056727b4540517,PMC,Molecular Subtyping of Human Rhinovirus in Children from Three Sub-Saharan African Countries,http://dx.doi.org/10.1128/JCM.00723-19,PMC6711929,31270180,CC BY,"The pathogenesis of human rhinovirus (HRV) during severe respiratory disease remains undefined; thus, we aimed to explore the relationship between the HRV molecular subtyping results obtained during severe and asymptomatic childhood infections. Nasopharyngeal/oropharyngeal swabs from children (1 to 59 months of age) hospitalized with pneumonia and from age-frequency-matched controls were collected between August 2011 and August 2013. Swabs were tested for respiratory pathogens, including HRV, using quantitative real-time PCR assays. HRV-positive samples were sequenced for phylogenetic analysis by targeting the 5′ noncoding region (5′NCR). Our data showed that there were no differences in the prevalence of HRV detection among cases and controls (21% versus 20%, P = 0.693); however, among children 13 to 59 months old, HRV detection was more often case associated (21% versus 16%; P = 0.009), with the results mainly driven by HRV-C (12% versus 7%; P = 0.001). Overall, there were no differences in the results of molecular subtyping of the HRV species prevalence among cases (for HRV-A, 48%; for HRV-B, 7%; for HRV-C, 45%) and controls (for HRV-A, 45%; for HRV-B, 10%; for HRV-C, 45% [P = 0.496]). Those with pneumonia and HRV-C were older (12.1 versus 9.4 months, P = 0.033) and more likely to present with wheeze (35% versus 25%, P = 0.031) than those with HRV-A cases. Thus, the rate of HRV detection was high, with similar degrees of genetic diversity among cases and controls, confounding the interpretation of the presence of HRV in nasopharyngeal samples for attribution of a causal role in the pathogenesis of severe pneumonia in infants. However, among children 13 to 59 months of age, HRV detection, in particular, HRV-C detection, was associated with case status, especially among children with wheezing disease.",2019 Aug 26,"['Baillie, Vicky L.', 'Moore, David P.', 'Mathunjwa, Azwifarwi', 'Morailane, Palesa', 'Simões, Eric A. F.', 'Madhi, Shabir A.']",J Clin Microbiol,,,False
e548e1afab98cbee2c2516b330839ed743b5c45e,PMC,Molecular Subtyping of Human Rhinovirus in Children from Three Sub-Saharan African Countries,http://dx.doi.org/10.1128/JCM.00723-19,PMC6711929,31270180,CC BY,"The pathogenesis of human rhinovirus (HRV) during severe respiratory disease remains undefined; thus, we aimed to explore the relationship between the HRV molecular subtyping results obtained during severe and asymptomatic childhood infections. Nasopharyngeal/oropharyngeal swabs from children (1 to 59 months of age) hospitalized with pneumonia and from age-frequency-matched controls were collected between August 2011 and August 2013. Swabs were tested for respiratory pathogens, including HRV, using quantitative real-time PCR assays. HRV-positive samples were sequenced for phylogenetic analysis by targeting the 5′ noncoding region (5′NCR). Our data showed that there were no differences in the prevalence of HRV detection among cases and controls (21% versus 20%, P = 0.693); however, among children 13 to 59 months old, HRV detection was more often case associated (21% versus 16%; P = 0.009), with the results mainly driven by HRV-C (12% versus 7%; P = 0.001). Overall, there were no differences in the results of molecular subtyping of the HRV species prevalence among cases (for HRV-A, 48%; for HRV-B, 7%; for HRV-C, 45%) and controls (for HRV-A, 45%; for HRV-B, 10%; for HRV-C, 45% [P = 0.496]). Those with pneumonia and HRV-C were older (12.1 versus 9.4 months, P = 0.033) and more likely to present with wheeze (35% versus 25%, P = 0.031) than those with HRV-A cases. Thus, the rate of HRV detection was high, with similar degrees of genetic diversity among cases and controls, confounding the interpretation of the presence of HRV in nasopharyngeal samples for attribution of a causal role in the pathogenesis of severe pneumonia in infants. However, among children 13 to 59 months of age, HRV detection, in particular, HRV-C detection, was associated with case status, especially among children with wheezing disease.",2019 Aug 26,"['Baillie, Vicky L.', 'Moore, David P.', 'Mathunjwa, Azwifarwi', 'Morailane, Palesa', 'Simões, Eric A. F.', 'Madhi, Shabir A.']",J Clin Microbiol,,,False
9c8f065d3f520a467940099c826e3122b315bfa3,PMC,Molecular Subtyping of Human Rhinovirus in Children from Three Sub-Saharan African Countries,http://dx.doi.org/10.1128/JCM.00723-19,PMC6711929,31270180,CC BY,"The pathogenesis of human rhinovirus (HRV) during severe respiratory disease remains undefined; thus, we aimed to explore the relationship between the HRV molecular subtyping results obtained during severe and asymptomatic childhood infections. Nasopharyngeal/oropharyngeal swabs from children (1 to 59 months of age) hospitalized with pneumonia and from age-frequency-matched controls were collected between August 2011 and August 2013. Swabs were tested for respiratory pathogens, including HRV, using quantitative real-time PCR assays. HRV-positive samples were sequenced for phylogenetic analysis by targeting the 5′ noncoding region (5′NCR). Our data showed that there were no differences in the prevalence of HRV detection among cases and controls (21% versus 20%, P = 0.693); however, among children 13 to 59 months old, HRV detection was more often case associated (21% versus 16%; P = 0.009), with the results mainly driven by HRV-C (12% versus 7%; P = 0.001). Overall, there were no differences in the results of molecular subtyping of the HRV species prevalence among cases (for HRV-A, 48%; for HRV-B, 7%; for HRV-C, 45%) and controls (for HRV-A, 45%; for HRV-B, 10%; for HRV-C, 45% [P = 0.496]). Those with pneumonia and HRV-C were older (12.1 versus 9.4 months, P = 0.033) and more likely to present with wheeze (35% versus 25%, P = 0.031) than those with HRV-A cases. Thus, the rate of HRV detection was high, with similar degrees of genetic diversity among cases and controls, confounding the interpretation of the presence of HRV in nasopharyngeal samples for attribution of a causal role in the pathogenesis of severe pneumonia in infants. However, among children 13 to 59 months of age, HRV detection, in particular, HRV-C detection, was associated with case status, especially among children with wheezing disease.",2019 Aug 26,"['Baillie, Vicky L.', 'Moore, David P.', 'Mathunjwa, Azwifarwi', 'Morailane, Palesa', 'Simões, Eric A. F.', 'Madhi, Shabir A.']",J Clin Microbiol,,,False
d7e999bd304a6ba26fe3bbe99b5ef7fc97150cf5,PMC,Molecular Subtyping of Human Rhinovirus in Children from Three Sub-Saharan African Countries,http://dx.doi.org/10.1128/JCM.00723-19,PMC6711929,31270180,CC BY,"The pathogenesis of human rhinovirus (HRV) during severe respiratory disease remains undefined; thus, we aimed to explore the relationship between the HRV molecular subtyping results obtained during severe and asymptomatic childhood infections. Nasopharyngeal/oropharyngeal swabs from children (1 to 59 months of age) hospitalized with pneumonia and from age-frequency-matched controls were collected between August 2011 and August 2013. Swabs were tested for respiratory pathogens, including HRV, using quantitative real-time PCR assays. HRV-positive samples were sequenced for phylogenetic analysis by targeting the 5′ noncoding region (5′NCR). Our data showed that there were no differences in the prevalence of HRV detection among cases and controls (21% versus 20%, P = 0.693); however, among children 13 to 59 months old, HRV detection was more often case associated (21% versus 16%; P = 0.009), with the results mainly driven by HRV-C (12% versus 7%; P = 0.001). Overall, there were no differences in the results of molecular subtyping of the HRV species prevalence among cases (for HRV-A, 48%; for HRV-B, 7%; for HRV-C, 45%) and controls (for HRV-A, 45%; for HRV-B, 10%; for HRV-C, 45% [P = 0.496]). Those with pneumonia and HRV-C were older (12.1 versus 9.4 months, P = 0.033) and more likely to present with wheeze (35% versus 25%, P = 0.031) than those with HRV-A cases. Thus, the rate of HRV detection was high, with similar degrees of genetic diversity among cases and controls, confounding the interpretation of the presence of HRV in nasopharyngeal samples for attribution of a causal role in the pathogenesis of severe pneumonia in infants. However, among children 13 to 59 months of age, HRV detection, in particular, HRV-C detection, was associated with case status, especially among children with wheezing disease.",2019 Aug 26,"['Baillie, Vicky L.', 'Moore, David P.', 'Mathunjwa, Azwifarwi', 'Morailane, Palesa', 'Simões, Eric A. F.', 'Madhi, Shabir A.']",J Clin Microbiol,,,False
c26ebc984e45528b970599075a2ddaebcad085e7,PMC,Molecular Subtyping of Human Rhinovirus in Children from Three Sub-Saharan African Countries,http://dx.doi.org/10.1128/JCM.00723-19,PMC6711929,31270180,CC BY,"The pathogenesis of human rhinovirus (HRV) during severe respiratory disease remains undefined; thus, we aimed to explore the relationship between the HRV molecular subtyping results obtained during severe and asymptomatic childhood infections. Nasopharyngeal/oropharyngeal swabs from children (1 to 59 months of age) hospitalized with pneumonia and from age-frequency-matched controls were collected between August 2011 and August 2013. Swabs were tested for respiratory pathogens, including HRV, using quantitative real-time PCR assays. HRV-positive samples were sequenced for phylogenetic analysis by targeting the 5′ noncoding region (5′NCR). Our data showed that there were no differences in the prevalence of HRV detection among cases and controls (21% versus 20%, P = 0.693); however, among children 13 to 59 months old, HRV detection was more often case associated (21% versus 16%; P = 0.009), with the results mainly driven by HRV-C (12% versus 7%; P = 0.001). Overall, there were no differences in the results of molecular subtyping of the HRV species prevalence among cases (for HRV-A, 48%; for HRV-B, 7%; for HRV-C, 45%) and controls (for HRV-A, 45%; for HRV-B, 10%; for HRV-C, 45% [P = 0.496]). Those with pneumonia and HRV-C were older (12.1 versus 9.4 months, P = 0.033) and more likely to present with wheeze (35% versus 25%, P = 0.031) than those with HRV-A cases. Thus, the rate of HRV detection was high, with similar degrees of genetic diversity among cases and controls, confounding the interpretation of the presence of HRV in nasopharyngeal samples for attribution of a causal role in the pathogenesis of severe pneumonia in infants. However, among children 13 to 59 months of age, HRV detection, in particular, HRV-C detection, was associated with case status, especially among children with wheezing disease.",2019 Aug 26,"['Baillie, Vicky L.', 'Moore, David P.', 'Mathunjwa, Azwifarwi', 'Morailane, Palesa', 'Simões, Eric A. F.', 'Madhi, Shabir A.']",J Clin Microbiol,,,False
cd3c7bc4656919fc9d8564bff6693b24631f97d7,PMC,"Interferon-Induced Protein 44 Interacts with Cellular FK506-Binding Protein 5, Negatively Regulates Host Antiviral Responses, and Supports Virus Replication",http://dx.doi.org/10.1128/mBio.01839-19,PMC6712396,31455651,CC BY,"Using multiple viral systems, and performing silencing approaches, overexpression approaches, and experiments in knockout cells, we report, for the first time, that interferon (IFN)-induced protein 44 (IFI44) positively affects virus production and negatively modulates innate immune responses induced after viral infections. Moreover, IFI44 is able to rescue poly(I·C)- and IFN-mediated inhibition of virus growth. Furthermore, we report a novel interaction of IFI44 with the cellular factor FK506-binding protein 5 (FKBP5), which binds to cellular kinases such as the inhibitor of nuclear factor kappa B (IκB) kinases (IKKα, IKKβ, and IKKε). Importantly, in the presence of FKBP5, IFI44 decreases the ability of IKKβ to phosphorylate IκBα and the ability of IKKε to phosphorylate interferon regulatory factor 3 (IRF-3), providing a novel mechanism for the function of IFI44 in negatively modulating IFN responses. Remarkably, these new IFI44 functions may have implications for diseases associated with excessive immune signaling and for controlling virus infections mediated by IFN responses.",2019 Aug 27,"['DeDiego, Marta L.', 'Nogales, Aitor', 'Martinez-Sobrido, Luis', 'Topham, David J.']",mBio,,,True
3f8c21c1bb4ebf5a427090d17a9e6e7e5cf5ec85,PMC,"Interferon-Induced Protein 44 Interacts with Cellular FK506-Binding Protein 5, Negatively Regulates Host Antiviral Responses, and Supports Virus Replication",http://dx.doi.org/10.1128/mBio.01839-19,PMC6712396,31455651,CC BY,"Using multiple viral systems, and performing silencing approaches, overexpression approaches, and experiments in knockout cells, we report, for the first time, that interferon (IFN)-induced protein 44 (IFI44) positively affects virus production and negatively modulates innate immune responses induced after viral infections. Moreover, IFI44 is able to rescue poly(I·C)- and IFN-mediated inhibition of virus growth. Furthermore, we report a novel interaction of IFI44 with the cellular factor FK506-binding protein 5 (FKBP5), which binds to cellular kinases such as the inhibitor of nuclear factor kappa B (IκB) kinases (IKKα, IKKβ, and IKKε). Importantly, in the presence of FKBP5, IFI44 decreases the ability of IKKβ to phosphorylate IκBα and the ability of IKKε to phosphorylate interferon regulatory factor 3 (IRF-3), providing a novel mechanism for the function of IFI44 in negatively modulating IFN responses. Remarkably, these new IFI44 functions may have implications for diseases associated with excessive immune signaling and for controlling virus infections mediated by IFN responses.",2019 Aug 27,"['DeDiego, Marta L.', 'Nogales, Aitor', 'Martinez-Sobrido, Luis', 'Topham, David J.']",mBio,,,False
eac69a8cc9922a8c01879aead41af65c437ed76e,PMC,"Interferon-Induced Protein 44 Interacts with Cellular FK506-Binding Protein 5, Negatively Regulates Host Antiviral Responses, and Supports Virus Replication",http://dx.doi.org/10.1128/mBio.01839-19,PMC6712396,31455651,CC BY,"Using multiple viral systems, and performing silencing approaches, overexpression approaches, and experiments in knockout cells, we report, for the first time, that interferon (IFN)-induced protein 44 (IFI44) positively affects virus production and negatively modulates innate immune responses induced after viral infections. Moreover, IFI44 is able to rescue poly(I·C)- and IFN-mediated inhibition of virus growth. Furthermore, we report a novel interaction of IFI44 with the cellular factor FK506-binding protein 5 (FKBP5), which binds to cellular kinases such as the inhibitor of nuclear factor kappa B (IκB) kinases (IKKα, IKKβ, and IKKε). Importantly, in the presence of FKBP5, IFI44 decreases the ability of IKKβ to phosphorylate IκBα and the ability of IKKε to phosphorylate interferon regulatory factor 3 (IRF-3), providing a novel mechanism for the function of IFI44 in negatively modulating IFN responses. Remarkably, these new IFI44 functions may have implications for diseases associated with excessive immune signaling and for controlling virus infections mediated by IFN responses.",2019 Aug 27,"['DeDiego, Marta L.', 'Nogales, Aitor', 'Martinez-Sobrido, Luis', 'Topham, David J.']",mBio,,,False
6f3c8b1769538d673f8eee7d1272fdea510fa445,PMC,"Interferon-Induced Protein 44 Interacts with Cellular FK506-Binding Protein 5, Negatively Regulates Host Antiviral Responses, and Supports Virus Replication",http://dx.doi.org/10.1128/mBio.01839-19,PMC6712396,31455651,CC BY,"Using multiple viral systems, and performing silencing approaches, overexpression approaches, and experiments in knockout cells, we report, for the first time, that interferon (IFN)-induced protein 44 (IFI44) positively affects virus production and negatively modulates innate immune responses induced after viral infections. Moreover, IFI44 is able to rescue poly(I·C)- and IFN-mediated inhibition of virus growth. Furthermore, we report a novel interaction of IFI44 with the cellular factor FK506-binding protein 5 (FKBP5), which binds to cellular kinases such as the inhibitor of nuclear factor kappa B (IκB) kinases (IKKα, IKKβ, and IKKε). Importantly, in the presence of FKBP5, IFI44 decreases the ability of IKKβ to phosphorylate IκBα and the ability of IKKε to phosphorylate interferon regulatory factor 3 (IRF-3), providing a novel mechanism for the function of IFI44 in negatively modulating IFN responses. Remarkably, these new IFI44 functions may have implications for diseases associated with excessive immune signaling and for controlling virus infections mediated by IFN responses.",2019 Aug 27,"['DeDiego, Marta L.', 'Nogales, Aitor', 'Martinez-Sobrido, Luis', 'Topham, David J.']",mBio,,,False
32ba544e884f13b65fe50c40dafb3983f1144c15,PMC,"Interferon-Induced Protein 44 Interacts with Cellular FK506-Binding Protein 5, Negatively Regulates Host Antiviral Responses, and Supports Virus Replication",http://dx.doi.org/10.1128/mBio.01839-19,PMC6712396,31455651,CC BY,"Using multiple viral systems, and performing silencing approaches, overexpression approaches, and experiments in knockout cells, we report, for the first time, that interferon (IFN)-induced protein 44 (IFI44) positively affects virus production and negatively modulates innate immune responses induced after viral infections. Moreover, IFI44 is able to rescue poly(I·C)- and IFN-mediated inhibition of virus growth. Furthermore, we report a novel interaction of IFI44 with the cellular factor FK506-binding protein 5 (FKBP5), which binds to cellular kinases such as the inhibitor of nuclear factor kappa B (IκB) kinases (IKKα, IKKβ, and IKKε). Importantly, in the presence of FKBP5, IFI44 decreases the ability of IKKβ to phosphorylate IκBα and the ability of IKKε to phosphorylate interferon regulatory factor 3 (IRF-3), providing a novel mechanism for the function of IFI44 in negatively modulating IFN responses. Remarkably, these new IFI44 functions may have implications for diseases associated with excessive immune signaling and for controlling virus infections mediated by IFN responses.",2019 Aug 27,"['DeDiego, Marta L.', 'Nogales, Aitor', 'Martinez-Sobrido, Luis', 'Topham, David J.']",mBio,,,False
c78582db242af67ad0fd574dbb68df5465d96d05,PMC,"Interferon-Induced Protein 44 Interacts with Cellular FK506-Binding Protein 5, Negatively Regulates Host Antiviral Responses, and Supports Virus Replication",http://dx.doi.org/10.1128/mBio.01839-19,PMC6712396,31455651,CC BY,"Using multiple viral systems, and performing silencing approaches, overexpression approaches, and experiments in knockout cells, we report, for the first time, that interferon (IFN)-induced protein 44 (IFI44) positively affects virus production and negatively modulates innate immune responses induced after viral infections. Moreover, IFI44 is able to rescue poly(I·C)- and IFN-mediated inhibition of virus growth. Furthermore, we report a novel interaction of IFI44 with the cellular factor FK506-binding protein 5 (FKBP5), which binds to cellular kinases such as the inhibitor of nuclear factor kappa B (IκB) kinases (IKKα, IKKβ, and IKKε). Importantly, in the presence of FKBP5, IFI44 decreases the ability of IKKβ to phosphorylate IκBα and the ability of IKKε to phosphorylate interferon regulatory factor 3 (IRF-3), providing a novel mechanism for the function of IFI44 in negatively modulating IFN responses. Remarkably, these new IFI44 functions may have implications for diseases associated with excessive immune signaling and for controlling virus infections mediated by IFN responses.",2019 Aug 27,"['DeDiego, Marta L.', 'Nogales, Aitor', 'Martinez-Sobrido, Luis', 'Topham, David J.']",mBio,,,False
d57066fb6b0be503b07e3d19f20166d06af60b18,PMC,A Structure-Function Diversity Survey of the RNA-Dependent RNA Polymerases From the Positive-Strand RNA Viruses,http://dx.doi.org/10.3389/fmicb.2019.01945,PMC6713929,31507560,CC BY,"The RNA-dependent RNA polymerases (RdRPs) encoded by the RNA viruses are a unique class of nucleic acid polymerases. Each viral RdRP contains a 500–600 residue catalytic module with palm, fingers, and thumb domains forming an encircled human right hand architecture. Seven polymerase catalytic motifs are located in the RdRP palm and fingers domains, comprising the most conserved parts of the RdRP and are responsible for the RNA-only specificity in catalysis. Functional regions are often found fused to the RdRP catalytic module, resulting in a high level of diversity in RdRP global structure and regulatory mechanism. In this review, we surveyed all 46 RdRP-sequence available virus families of the positive-strand RNA viruses listed in the 2018b collection of the International Committee on Virus Taxonomy (ICTV) and chose a total of 49 RdRPs as representatives. By locating hallmark residues in RdRP catalytic motifs and by referencing structural and functional information in the literature, we were able to estimate the N- and C-terminal boundaries of the catalytic module in these RdRPs, which in turn serve as reference points to predict additional functional regions beyond the catalytic module. Interestingly, a large number of virus families may have additional regions fused to the RdRP N-terminus, while only a few of them have such regions on the C-terminal side of the RdRP. The current knowledge on these additional regions, either in three-dimensional (3D) structure or in function, is quite limited. In the five RdRP-structure available virus families in the positive-strand RNA viruses, only the Flaviviridae family has the 3D structural information resolved for such regions. Hence, future efforts to solve full-length RdRP structures containing these regions and to dissect the functional contribution of them are necessary to improve the overall understanding of the RdRP proteins as an evolutionarily integrated group, and our analyses here may serve as a guideline for selecting representative RdRP systems in these studies.",2019 Aug 22,"['Jia, Hengxia', 'Gong, Peng']",Front Microbiol,,,True
19c5afd0792de2eeb9ac08afbb1dfe184386af26,PMC,The Role of Non-animal Origin Feed Ingredients in Transmission of Viral Pathogens of Swine: A Review of Scientific Literature,http://dx.doi.org/10.3389/fvets.2019.00273,PMC6714588,31508430,CC BY,"The emergence of porcine epidemic diarrhea (PED) in commercial swine in North America and growing concerns about the potential for the introduction of African swine fever (ASF) from China, the European Union, or other affected regions has put a spotlight on the possible role of contaminated feed and feed ingredients in the introduction and transmission of viral swine pathogens. This paper systematically reviews the scientific literature regarding whether non-animal origin ingredients of commercial swine feed could introduce or transmit viral pathogens of swine into or within the United States. The purpose of this review is to identify, evaluate, and summarize the relevant scientific knowledge, published through March 2018, and to identify information gaps and research needs, thereby making the available evidence more accessible to policy makers, the swine industry, and the scientific community. A total of 26 documents were selected for the final review process, which included experimental studies, case reports, epidemiological investigations, and scientific opinion, among others. The review found that the scientific literature has addressed some critical experimental questions pertaining to transmission of swine viruses via feed and feed ingredients, but the current body of scientific knowledge lacks conclusive evidence of virus contamination of non-animal origin feed ingredients of commercial swine feed, particularly for imported commodities, and further investigation into the epidemiology of virus transmission via feed to swine under field conditions through natural feeding behavior is warranted. Additional studies of how imported ingredients of commercial swine feed are sourced, processed, transported and, thus, contaminated prior to importation into the United States are needed. Moving forward, studies designed to examine the likely source(s) of contamination and subsequent virus mitigation steps in processing and post-processing may be the most fruitful focus of research.",2019 Aug 22,"['Gordon, Rebecca K.', 'Kotowski, Ingrid K.', 'Coulson, Kari F.', 'Link, Donald', 'MacKenzie, Alexandra', 'Bowling-Heyward, Joyce']",Front Vet Sci,,,False
461e14fcd69e84dfcc444f0ab92632688997b40d,PMC,The Role of Non-animal Origin Feed Ingredients in Transmission of Viral Pathogens of Swine: A Review of Scientific Literature,http://dx.doi.org/10.3389/fvets.2019.00273,PMC6714588,31508430,CC BY,"The emergence of porcine epidemic diarrhea (PED) in commercial swine in North America and growing concerns about the potential for the introduction of African swine fever (ASF) from China, the European Union, or other affected regions has put a spotlight on the possible role of contaminated feed and feed ingredients in the introduction and transmission of viral swine pathogens. This paper systematically reviews the scientific literature regarding whether non-animal origin ingredients of commercial swine feed could introduce or transmit viral pathogens of swine into or within the United States. The purpose of this review is to identify, evaluate, and summarize the relevant scientific knowledge, published through March 2018, and to identify information gaps and research needs, thereby making the available evidence more accessible to policy makers, the swine industry, and the scientific community. A total of 26 documents were selected for the final review process, which included experimental studies, case reports, epidemiological investigations, and scientific opinion, among others. The review found that the scientific literature has addressed some critical experimental questions pertaining to transmission of swine viruses via feed and feed ingredients, but the current body of scientific knowledge lacks conclusive evidence of virus contamination of non-animal origin feed ingredients of commercial swine feed, particularly for imported commodities, and further investigation into the epidemiology of virus transmission via feed to swine under field conditions through natural feeding behavior is warranted. Additional studies of how imported ingredients of commercial swine feed are sourced, processed, transported and, thus, contaminated prior to importation into the United States are needed. Moving forward, studies designed to examine the likely source(s) of contamination and subsequent virus mitigation steps in processing and post-processing may be the most fruitful focus of research.",2019 Aug 22,"['Gordon, Rebecca K.', 'Kotowski, Ingrid K.', 'Coulson, Kari F.', 'Link, Donald', 'MacKenzie, Alexandra', 'Bowling-Heyward, Joyce']",Front Vet Sci,,,True
f0db088c90145abdb3d3709fa3beda244c80f100,PMC,Comparative Analysis of Gene Expression in Virulent and Attenuated Strains of Infectious Bronchitis Virus at Subcodon Resolution,http://dx.doi.org/10.1128/JVI.00714-19,PMC6714804,31243124,CC BY,"Like all coronaviruses, avian infectious bronchitis virus (IBV) possesses a long, single-stranded, positive-sense RNA genome (∼27 kb) and has a complex replication strategy that includes the production of a nested set of subgenomic mRNAs (sgmRNAs). Here, we used whole-transcriptome sequencing (RNASeq) and ribosome profiling (RiboSeq) to delineate gene expression in the IBV M41-CK and Beau-R strains at subcodon resolution. RNASeq facilitated a comparative analysis of viral RNA synthesis and revealed two novel transcription junction sites in the attenuated Beau-R strain, one of which would generate a sgmRNA encoding a ribosomally occupied open reading frame (dORF) located downstream of the nucleocapsid coding region. RiboSeq permitted quantification of the translational efficiency of virus gene expression and identified, for the first time, sites of ribosomal pausing on the genome. Quantification of reads flanking the programmed ribosomal frameshifting (PRF) signal at the genomic RNA ORF1a/ORF1b junction revealed that PRF in IBV is highly efficient (33 to 40%). Triplet phasing of RiboSeq data allowed precise determination of reading frames and revealed the translation of two ORFs (ORF4b and ORF4c on sgmRNA IR), which are widely conserved across IBV isolates. Analysis of differential gene expression in infected primary chick kidney cells indicated that the host cell response to IBV occurs primarily at the level of transcription, with global upregulation of immune-related mRNA transcripts following infection and comparatively modest changes in the translation efficiencies of host genes. Cellular genes and gene networks differentially expressed during virus infection were also identified, giving insights into the host cell response to IBV infection. IMPORTANCE IBV is a major avian pathogen and presents a substantial economic burden to the poultry industry. Improved vaccination strategies are urgently needed to curb the global spread of this virus, and the development of suitable vaccine candidates will be aided by an improved understanding of IBV molecular biology. Our high-resolution data have enabled a precise study of transcription and translation in cells infected with both pathogenic and attenuated forms of IBV and expand our understanding of gammacoronaviral gene expression. We demonstrate that gene expression shows considerable intraspecies variation, with single nucleotide polymorphisms being associated with altered production of sgmRNA transcripts, and our RiboSeq data sets enabled us to uncover novel ribosomally occupied ORFs in both strains. The numerous cellular genes and gene networks found to be differentially expressed during virus infection provide insights into the host cell response to IBV infection.",2019 Aug 28,"['Dinan, Adam M.', 'Keep, Sarah', 'Bickerton, Erica', 'Britton, Paul', 'Firth, Andrew E.', 'Brierley, Ian']",J Virol,,,True
f678c06b6289cc9940ffc9f2007bb58c58773563,PMC,Comparative Analysis of Gene Expression in Virulent and Attenuated Strains of Infectious Bronchitis Virus at Subcodon Resolution,http://dx.doi.org/10.1128/JVI.00714-19,PMC6714804,31243124,CC BY,"Like all coronaviruses, avian infectious bronchitis virus (IBV) possesses a long, single-stranded, positive-sense RNA genome (∼27 kb) and has a complex replication strategy that includes the production of a nested set of subgenomic mRNAs (sgmRNAs). Here, we used whole-transcriptome sequencing (RNASeq) and ribosome profiling (RiboSeq) to delineate gene expression in the IBV M41-CK and Beau-R strains at subcodon resolution. RNASeq facilitated a comparative analysis of viral RNA synthesis and revealed two novel transcription junction sites in the attenuated Beau-R strain, one of which would generate a sgmRNA encoding a ribosomally occupied open reading frame (dORF) located downstream of the nucleocapsid coding region. RiboSeq permitted quantification of the translational efficiency of virus gene expression and identified, for the first time, sites of ribosomal pausing on the genome. Quantification of reads flanking the programmed ribosomal frameshifting (PRF) signal at the genomic RNA ORF1a/ORF1b junction revealed that PRF in IBV is highly efficient (33 to 40%). Triplet phasing of RiboSeq data allowed precise determination of reading frames and revealed the translation of two ORFs (ORF4b and ORF4c on sgmRNA IR), which are widely conserved across IBV isolates. Analysis of differential gene expression in infected primary chick kidney cells indicated that the host cell response to IBV occurs primarily at the level of transcription, with global upregulation of immune-related mRNA transcripts following infection and comparatively modest changes in the translation efficiencies of host genes. Cellular genes and gene networks differentially expressed during virus infection were also identified, giving insights into the host cell response to IBV infection. IMPORTANCE IBV is a major avian pathogen and presents a substantial economic burden to the poultry industry. Improved vaccination strategies are urgently needed to curb the global spread of this virus, and the development of suitable vaccine candidates will be aided by an improved understanding of IBV molecular biology. Our high-resolution data have enabled a precise study of transcription and translation in cells infected with both pathogenic and attenuated forms of IBV and expand our understanding of gammacoronaviral gene expression. We demonstrate that gene expression shows considerable intraspecies variation, with single nucleotide polymorphisms being associated with altered production of sgmRNA transcripts, and our RiboSeq data sets enabled us to uncover novel ribosomally occupied ORFs in both strains. The numerous cellular genes and gene networks found to be differentially expressed during virus infection provide insights into the host cell response to IBV infection.",2019 Aug 28,"['Dinan, Adam M.', 'Keep, Sarah', 'Bickerton, Erica', 'Britton, Paul', 'Firth, Andrew E.', 'Brierley, Ian']",J Virol,,,True
fafb26c5bdadd0edae3ce7b42f89aa52fefa06e3,PMC,Specific increase of Fusobacterium in the faecal microbiota of neonatal calves infected with Cryptosporidium parvum,http://dx.doi.org/10.1038/s41598-019-48969-6,PMC6715637,31467354,CC BY,"The faecal microbiota plays a critical role in host health, with alterations in the human faecal microbial composition associated with various conditions, particularly diarrhoeal diseases. However, little is known about microbial changes during cryptosporidiosis, one of the most important diarrhoeal diseases caused by protozoa in cattle. In this study, alterations in the faecal microbiota of neonatal calves as a result of Cryptosporidium parvum infection were investigated on a C. parvum-positive farm. Comparisons were made among groups of C. parvum-infected, rotavirus-infected, and the pathogen-negative calves. A specific increase in the abundance of Fusobacterium was observed in the faecal microbiota of C. parvum-infected animals. Diarrhoea severity increased in accordance with the abundance of C. parvum and Fusobacterium. Moreover, the specific increase of Fusobacterium appeared to be a universal feature of C. parvum infection, since neonatal calves from geographically separated areas showed the same result. These observations indicated that the growth of Fusobacterium may be an important aggravating factor of cryptosporidiosis.",2019 Aug 29,"['Ichikawa-Seki, Madoka', 'Motooka, Daisuke', 'Kinami, Aiko', 'Murakoshi, Fumi', 'Takahashi, Yoko', 'Aita, Junya', 'Hayashi, Kei', 'Tashibu, Atsushi', 'Nakamura, Shota', 'Iida, Tetsuya', 'Horii, Toshihiro', 'Nishikawa, Yoshifumi']",Sci Rep,,,False
c056bf64c107109def04dd9488e05b83a7742139,PMC,Specific increase of Fusobacterium in the faecal microbiota of neonatal calves infected with Cryptosporidium parvum,http://dx.doi.org/10.1038/s41598-019-48969-6,PMC6715637,31467354,CC BY,"The faecal microbiota plays a critical role in host health, with alterations in the human faecal microbial composition associated with various conditions, particularly diarrhoeal diseases. However, little is known about microbial changes during cryptosporidiosis, one of the most important diarrhoeal diseases caused by protozoa in cattle. In this study, alterations in the faecal microbiota of neonatal calves as a result of Cryptosporidium parvum infection were investigated on a C. parvum-positive farm. Comparisons were made among groups of C. parvum-infected, rotavirus-infected, and the pathogen-negative calves. A specific increase in the abundance of Fusobacterium was observed in the faecal microbiota of C. parvum-infected animals. Diarrhoea severity increased in accordance with the abundance of C. parvum and Fusobacterium. Moreover, the specific increase of Fusobacterium appeared to be a universal feature of C. parvum infection, since neonatal calves from geographically separated areas showed the same result. These observations indicated that the growth of Fusobacterium may be an important aggravating factor of cryptosporidiosis.",2019 Aug 29,"['Ichikawa-Seki, Madoka', 'Motooka, Daisuke', 'Kinami, Aiko', 'Murakoshi, Fumi', 'Takahashi, Yoko', 'Aita, Junya', 'Hayashi, Kei', 'Tashibu, Atsushi', 'Nakamura, Shota', 'Iida, Tetsuya', 'Horii, Toshihiro', 'Nishikawa, Yoshifumi']",Sci Rep,,,True
c756b061cd3d68d5167d5f8bec332d2763fae0ac,PMC,Global research trends in microbiome-gut-brain axis during 2009–2018: a bibliometric and visualized study,http://dx.doi.org/10.1186/s12876-019-1076-z,PMC6716890,31470803,CC BY,"BACKGROUND: The pathways and mechanism by which associations between the gut microbiome and the brain, termed the microbiome-gut-brain axis (MGBA), are manifest but remain to be fully elucidated. This study aims to use bibliometric analysis to estimate the global activity within this rapidly developing field and to identify particular areas of focus that are of current relevance to the MGBA during the last decade (2009–2018). METHODS: The current study uses the Scopus for data collection. We used the key terms “microbiome-gut-brain axis” and its synonyms because we are concerned with MGBA per se as a new concept in research rather than related topics. A VOSviewer version 1.6.11 was used to visualize collaboration pattern between countries and authors, and evolving research topics by analysis of the term co-occurrence in the title and abstract of publications. RESULTS: Between 2009 and 2018, there were 51,504 published documents related to the microbiome, including 1713 articles related to the MGBA: 829 (48.4%) original articles, 658(38.4%) reviews, and 226 (13.2%) other articles such as notes, editorials or letters. The USA took the first place with 385 appearances, followed by Ireland (n = 161), China (n = 155), and Canada (n = 144).The overall citation h-index was 106, and the countries with the highest h-index values were the USA (69), Ireland (58), and Canada (43). The cluster analysis demonstrated that the dominant fields of the MGBA include four clusters with four research directions: “modeling MGBA in animal systems”, “interplay between the gut microbiota and the immune system”, “irritable bowel syndrome related to gut microbiota”, and “neurodegenerative diseases related to gut microbiota”. CONCLUSIONS: This study demonstrates that the research on the MGBA has been becoming progressively more extensive at global level over the past 10 years. Overall, our study found that a large amount of work on MGBA focused on immunomodulation, irritable bowel syndrome, and neurodevelopmental disorders. Despite considerable progress illustrating the communication between the gut microbiome and the brain over the past 10 years, many issues remain about their relevance for therapeutic intervention of many diseases.",2019 Aug 30,"['Zyoud, Sa’ed H.', 'Smale, Simon', 'Waring, W. Stephen', 'Sweileh, Waleed M.', 'Al-Jabi, Samah W.']",BMC Gastroenterol,,,True
8880ca1de9ca704b6b0af29fd6c181457663ac40,PMC,Respiratory viral infections and the risk of rheumatoid arthritis,http://dx.doi.org/10.1186/s13075-019-1977-9,PMC6716891,31470887,CC BY,"BACKGROUND: We aimed to investigate the effects of ambient respiratory viral infections in the general population on rheumatoid arthritis (RA) development. METHODS: Data of weekly incident RA (2012–2013) were obtained from the Korean National Health Insurance claims database, and those of weekly observations on eight respiratory viral infections were obtained from the Korea Centers for Disease Control and Prevention database. We estimated the percentage change in incident RA associated with ambient mean respiratory viral infections using a generalized linear model, after adjusting for time trend, air pollution, and meteorological data. RESULTS: A total of 24,117 cases of incident RA (mean age 54.7 years, 18,688 [77.5%] women) were analyzed. Ambient respiratory viral infections in the population were associated with a higher number of incident RA over time, and its effect peaked 6 or 7 weeks after exposure. Among the 8 viruses, parainfluenza virus (4.8% for 1% respiratory viral infection increase, 95% CI 1.6 to 8.1, P = .003), coronavirus (9.2%, 3.9 to 14.8, P < .001), and metapneumovirus (44%, 2.0 to 103.4, P = .038) were associated with increased number of incident RA. The impact of these respiratory viral infections remained significant in women (3.8%, 12.1%, and 67.4%, respectively, P < .05) and in older patients (10.7%, 14.6%, and 118.2%, respectively, P < .05). CONCLUSIONS: Ambient respiratory viral infections in the population were associated with an increased number of incident RA, especially in women and older patients, suggesting that respiratory viral infections can be a novel environmental risk factor for the development of RA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-019-1977-9) contains supplementary material, which is available to authorized users.",2019 Aug 30,"['Joo, Young Bin', 'Lim, Youn-Hee', 'Kim, Ki-Jo', 'Park, Kyung-Su', 'Park, Yune-Jung']",Arthritis Res Ther,,,True
5d1e7636378e32ba1d2228d2ec7b3f82ac2661e3,PMC,Beyond cells – The virome in the human holobiont,http://dx.doi.org/10.15698/mic2019.09.689,PMC6717880,31528630,CC BY,"Viromics, or viral metagenomics, is a relatively new and burgeoning field of research that studies the complete collection of viruses forming part of the microbiota in any given niche. It has strong foundations rooted in over a century of discoveries in the field of virology and recent advances in molecular biology and sequencing technologies. Historically, most studies have deconstructed the concept of viruses into a simplified perception of viral agents as mere pathogens, which demerits the scope of large-scale viromic analyses. Viruses are, in fact, much more than regular parasites. They are by far the most dynamic and abundant entity and the greatest killers on the planet, as well as the most effective geo-transforming genetic engineers and resource recyclers, acting on all life strata in any habitat. Yet, most of this uncanny viral world remains vastly unexplored to date, greatly hindered by the bewildering complexity inherent to such studies and the methodological and conceptual limitations. Viromic studies are just starting to address some of these issues but they still lag behind microbial metagenomics. In recent years, however, higher-throughput analysis and resequencing have rekindled interest in a field that is just starting to show its true potential. In this review, we take a look at the scientific and technological developments that led to the advent of viral and bacterial metagenomics with a particular, but not exclusive, focus on human viromics from an ecological perspective. We also address some of the most relevant challenges that current viral studies face and ponder on the future directions of the field.",,"['García-López, Rodrigo', 'Pérez-Brocal, Vicente', 'Moya, Andrés']",Microb Cell.; 6(9):373-396,,,True
39cf63270ea4247abd489125c9d3c78d8f400987,PMC,Analysis of IFITM-IFITM Interactions by a Flow Cytometry-Based FRET Assay,http://dx.doi.org/10.3390/ijms20163859,PMC6719045,31398796,CC BY,"The interferon-induced transmembrane proteins 1–3 (IFITM1–3) inhibit host cell entry of several viruses. However, it is incompletely understood how IFITM1–3 exert antiviral activity. Two phenylalanine residues, F75 and F78, within the intramembrane domain 1 (IM1) were previously shown to be required for IFITM3/IFITM3 interactions and for inhibition of viral entry, suggesting that IFITM/IFITM interactions might be pivotal to antiviral activity. Here, we employed a fluorescence resonance energy transfer (FRET) assay to analyze IFITM/IFITM interactions. For assay calibration, we equipped two cytosolic, non-interacting proteins, super yellow fluorescent protein (SYFP) and super cyan fluorescent protein (SCFP), with signals that target proteins to membrane rafts and also analyzed a SCFP-SYFP fusion protein. This strategy allowed us to discriminate background signals resulting from colocalization of proteins at membrane subdomains from signals elicited by protein–protein interactions. Coexpression of IFITM1–3 and IFITM5 fused to fluorescent proteins elicited strong FRET signals, and mutation of F75 and F78 in IFITM3 (mutant IFITM3-FF) abrogated antiviral activity, as expected, but did not alter cellular localization and FRET signals. Moreover, IFITM3-FF co-immunoprecipitated efficiently with wild type (wt) IFITM3, lending further support to the finding that lack of antiviral activity of IFITM3-FF was not due to altered membrane targeting or abrogated IFITM3-IFITM3 interactions. Collectively, we report an assay that allows quantifying IFITM/IFITM interactions. Moreover, we confirm residues F75 and F78 as critical for antiviral activity but also show that these residues are dispensable for IFITM3 membrane localization and IFITM3/IFITM3 interactions.",2019 Aug 8,"['Winkler, Michael', 'Wrensch, Florian', 'Bosch, Pascale', 'Knoth, Maike', 'Schindler, Michael', 'Gärtner, Sabine', 'Pöhlmann, Stefan']",Int J Mol Sci,,,True
c179446abc96980232e34b4e910f2c184301c07f,PMC,Global Mapping of H3K4 Trimethylation (H3K4me3) and Transcriptome Analysis Reveal Genes Involved in the Response to Epidemic Diarrhea Virus Infections in Pigs,http://dx.doi.org/10.3390/ani9080523,PMC6719071,31382472,CC BY,"SIMPLE SUMMARY: Porcine epidemic diarrhea virus seriously threatens the health of suckling pigs. In this study, global mapping of H3K4me3 and transcriptomic analyses in the jejunum of porcine epidemic diarrhea virus (PEDV)-infected and healthy piglets were performed by using chromatin immunoprecipitation sequencing and RNA-seq techniques. A subset of genes and H3K4 trimethylation (H3K4me3) histone modifications that are associated with PEDV infections were identified. The results revealed previously unknown and intriguing elements involved in the regulation of genes responsive to PEDV infections, which may aid in identifying key regulators and genetic resistant markers for PEDV infections. ABSTRACT: Porcine epidemic diarrhea virus (PEDV) is currently detected as the main pathogen causing severe diarrhea in pig farms. The phenotypic alterations induced by pathogenic infections are usually tightly linked with marked changes in epigenetic modification and gene expression. We performed global mapping of H3K4 trimethylation (H3K4me3) and transcriptomic analyses in the jejunum of PEDV-infected and healthy piglets using chromatin immunoprecipitation sequencing and RNA-seq techniques. A total of 1885 H3K4me3 peaks that are associated with 1723 genes were characterized. Moreover, 290 differentially expressed genes were identified, including 104 up-regulated and 186 down-regulated genes. Several antiviral genes including 2’-5’-oligoadenylate synthetase 1 (OAS1), 2’-5’-oligoadenylate synthetase 2 (OAS2), ephrin B2 (EFNB2), and CDC28 protein kinase regulatory subunit 1B (CKS1B) with higher H3K4me3 enrichment and expression levels in PEDV-infected samples suggested the potential roles of H3K4me3 deposition in promoting their expressions. Transcription factor annotation analysis highlighted the potential roles of two transcription factors interferon regulatory factor 8 (IRF8) and Kruppel like factor 4 (KLF4) in modulating the differential expression of genes involved in PEDV infection. The results provided novel insights into PEDV infection from the transcriptomic and epigenetic layers and revealed previously unknown and intriguing elements potentially involved in the host responses.",2019 Aug 2,"['Wang, Haifei', 'Yang, Li', 'Qu, Huan', 'Feng, Haiyue', 'Wu, Shenglong', 'Bao, Wenbin']",Animals (Basel),,,True
16bc9f7d66f4d6c4bf79568d0859611493158df1,PMC,Global Mapping of H3K4 Trimethylation (H3K4me3) and Transcriptome Analysis Reveal Genes Involved in the Response to Epidemic Diarrhea Virus Infections in Pigs,http://dx.doi.org/10.3390/ani9080523,PMC6719071,31382472,CC BY,"SIMPLE SUMMARY: Porcine epidemic diarrhea virus seriously threatens the health of suckling pigs. In this study, global mapping of H3K4me3 and transcriptomic analyses in the jejunum of porcine epidemic diarrhea virus (PEDV)-infected and healthy piglets were performed by using chromatin immunoprecipitation sequencing and RNA-seq techniques. A subset of genes and H3K4 trimethylation (H3K4me3) histone modifications that are associated with PEDV infections were identified. The results revealed previously unknown and intriguing elements involved in the regulation of genes responsive to PEDV infections, which may aid in identifying key regulators and genetic resistant markers for PEDV infections. ABSTRACT: Porcine epidemic diarrhea virus (PEDV) is currently detected as the main pathogen causing severe diarrhea in pig farms. The phenotypic alterations induced by pathogenic infections are usually tightly linked with marked changes in epigenetic modification and gene expression. We performed global mapping of H3K4 trimethylation (H3K4me3) and transcriptomic analyses in the jejunum of PEDV-infected and healthy piglets using chromatin immunoprecipitation sequencing and RNA-seq techniques. A total of 1885 H3K4me3 peaks that are associated with 1723 genes were characterized. Moreover, 290 differentially expressed genes were identified, including 104 up-regulated and 186 down-regulated genes. Several antiviral genes including 2’-5’-oligoadenylate synthetase 1 (OAS1), 2’-5’-oligoadenylate synthetase 2 (OAS2), ephrin B2 (EFNB2), and CDC28 protein kinase regulatory subunit 1B (CKS1B) with higher H3K4me3 enrichment and expression levels in PEDV-infected samples suggested the potential roles of H3K4me3 deposition in promoting their expressions. Transcription factor annotation analysis highlighted the potential roles of two transcription factors interferon regulatory factor 8 (IRF8) and Kruppel like factor 4 (KLF4) in modulating the differential expression of genes involved in PEDV infection. The results provided novel insights into PEDV infection from the transcriptomic and epigenetic layers and revealed previously unknown and intriguing elements potentially involved in the host responses.",2019 Aug 2,"['Wang, Haifei', 'Yang, Li', 'Qu, Huan', 'Feng, Haiyue', 'Wu, Shenglong', 'Bao, Wenbin']",Animals (Basel),,,False
3aed588044335032787a5eb91ee61afadcd4a006,PMC,"Effects of AntagomiRs on Different Lung Diseases in Human, Cellular, and Animal Models",http://dx.doi.org/10.3390/ijms20163938,PMC6719072,31412612,CC BY,"Introduction: MiRNAs have been shown to play a crucial role among lung cancer, pulmonary fibrosis, tuberculosis (TBC) infection, and bronchial hypersensitivity, thus including chronic obstructive pulmonary disease (COPD) and asthma. The oncogenic effect of several miRNAs has been recently ruled out. In order to act on miRNAs turnover, antagomiRs have been developed. Materials and methods: The systematic review was conducted under the PRISMA guidelines (registration number is: CRD42019134173). The PubMed database was searched between 1 January 2000 and 30 April 2019 under the following search strategy: (((antagomiR) OR (mirna antagonists) OR (mirna antagonist)) AND ((lung[MeSH Terms]) OR (“lung diseases”[MeSH Terms]))). We included original articles, published in English, whereas exclusion criteria included reviews, meta-analyses, single case reports, and studies published in a language other than English. Results and Conclusions: A total of 68 articles matching the inclusion criteria were retrieved. Overall, the use of antagomiR was seen to be efficient in downregulating the specific miRNA they are conceived for. The usefulness of antagomiRs was demonstrated in humans, animal models, and cell lines. To our best knowledge, this is the first article to encompass evidence regarding miRNAs and their respective antagomiRs in the lung, in order to provide readers a comprehensive review upon major lung disorders.",2019 Aug 13,"['Murdaca, Giuseppe', 'Tonacci, Alessandro', 'Negrini, Simone', 'Greco, Monica', 'Borro, Matteo', 'Puppo, Francesco', 'Gangemi, Sebastiano']",Int J Mol Sci,,,True
7e43122d298db29a31acc538436b5f3a10621995,PMC,Effect of Saccharomyces boulardii Supplementation on Performance and Physiological Traits of Holstein Calves under Heat Stress Conditions,http://dx.doi.org/10.3390/ani9080510,PMC6719173,31370319,CC BY,"SIMPLE SUMMARY: In this study, the effects of Saccharomyces boulardii (SB) supplement on the performance and physiological traits of Holstein calves under heat stress were investigated using a climatic chamber. We revealed that supplementation with SB incorporated into milk replacer can ameliorate the negative impact of heat stress on Holstein dairy calves by increasing dry matter intake (DMI), reducing rectal temperature and heart rate, and alleviating diarrhea via modulating pathogenic bacteria in the digestive tract. The results showed that SB can be used as an alternative anti-stressor in the diet of young dairy calves under heat stress (HS). ABSTRACT: The objective of this study was to determine the effects of Saccharomyces boulardii CNCM I-1079 (SB) as a feed additive on performance, diarrhea frequency, rectal temperature, heart rate, water consumption, cortisol level, and fecal bacteria population in Holstein calves (28 ± 1.6 days of age, body weight of 45.6 ± 1.44 kg, n = 16) under thermal neutral (TN) and heat stress (HS) conditions. During the TN period for 21 days (d 1 to 21), calves receiving SB showed quadratic or linear effects compared to the control group, showing higher dry matter intake (DMI, p = 0.002), and water consumption (p = 0.007) but lower frequency of fecal diarrhea (p = 0.008), rectal temperature (p < 0.001), heart rate (p < 0.001), and fecal microbiota at 21 day (Escherichia coli, p = 0.025; Enterobacteriaceae, p = 0.041). Meanwhile, calves exposed to HS for 7 days (d 22 to 28) receiving SB showed quadratic or linear effects compared to the control group, showing higher DMI (p = 0.002) but lower water consumption (p = 0.023), rectal temperature (p = 0.026), and cortisol level (p = 0.014). Our results suggest that live SB is useful in the livestock industry as an alternative to conventional medication (especially in times of suspected health problems) that can be added to milk replacer for young dairy calves experiencing HS.",2019 Jul 31,"['Lee, Jae-Sung', 'Kacem, Nouali', 'Kim, Won-Seob', 'Peng, Dong Qiao', 'Kim, Young-Jun', 'Joung, Youn-Geun', 'Lee, Chanhee', 'Lee, Hong-Gu']",Animals (Basel),,,True
e6e8794a68a07c15287a2ef2302241d6d6f7205a,PMC,Effect of Saccharomyces boulardii Supplementation on Performance and Physiological Traits of Holstein Calves under Heat Stress Conditions,http://dx.doi.org/10.3390/ani9080510,PMC6719173,31370319,CC BY,"SIMPLE SUMMARY: In this study, the effects of Saccharomyces boulardii (SB) supplement on the performance and physiological traits of Holstein calves under heat stress were investigated using a climatic chamber. We revealed that supplementation with SB incorporated into milk replacer can ameliorate the negative impact of heat stress on Holstein dairy calves by increasing dry matter intake (DMI), reducing rectal temperature and heart rate, and alleviating diarrhea via modulating pathogenic bacteria in the digestive tract. The results showed that SB can be used as an alternative anti-stressor in the diet of young dairy calves under heat stress (HS). ABSTRACT: The objective of this study was to determine the effects of Saccharomyces boulardii CNCM I-1079 (SB) as a feed additive on performance, diarrhea frequency, rectal temperature, heart rate, water consumption, cortisol level, and fecal bacteria population in Holstein calves (28 ± 1.6 days of age, body weight of 45.6 ± 1.44 kg, n = 16) under thermal neutral (TN) and heat stress (HS) conditions. During the TN period for 21 days (d 1 to 21), calves receiving SB showed quadratic or linear effects compared to the control group, showing higher dry matter intake (DMI, p = 0.002), and water consumption (p = 0.007) but lower frequency of fecal diarrhea (p = 0.008), rectal temperature (p < 0.001), heart rate (p < 0.001), and fecal microbiota at 21 day (Escherichia coli, p = 0.025; Enterobacteriaceae, p = 0.041). Meanwhile, calves exposed to HS for 7 days (d 22 to 28) receiving SB showed quadratic or linear effects compared to the control group, showing higher DMI (p = 0.002) but lower water consumption (p = 0.023), rectal temperature (p = 0.026), and cortisol level (p = 0.014). Our results suggest that live SB is useful in the livestock industry as an alternative to conventional medication (especially in times of suspected health problems) that can be added to milk replacer for young dairy calves experiencing HS.",2019 Jul 31,"['Lee, Jae-Sung', 'Kacem, Nouali', 'Kim, Won-Seob', 'Peng, Dong Qiao', 'Kim, Young-Jun', 'Joung, Youn-Geun', 'Lee, Chanhee', 'Lee, Hong-Gu']",Animals (Basel),,,False
72b1f124ded8f8297f0f02ea6dbc0f9b7b27873a,PMC,Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors,http://dx.doi.org/10.12688/wellcomeopenres.15268.2,PMC6719676,31489381,CC BY,"Background: Social contact patterns shape the transmission of respiratory infections spread via close interactions. There is a paucity of observational data from schools and households, particularly in developing countries. Portable wireless sensors can record unbiased proximity events between individuals facing each other, shedding light on pathways of infection transmission. Design and methods: The aim is to characterize face-to-face contact patterns that may shape the transmission of respiratory infections in schools and households in Kilifi, Kenya. Two schools, one each from a rural and urban area, will be purposively selected. From each school, 350 students will be randomly selected proportional to class size and gender to participate. Nine index students from each school will be randomly selected and followed-up to their households. All index household residents will be recruited into the study. A further 3-5 neighbouring households will also be recruited to give a maximum of 350 participants per household setting. The sample size per site is limited by the number of sensors available for data collection. Each participant will wear a wireless proximity sensor lying on their chest area for 7 consecutive days. Data on proximal dyadic interactions will be collected automatically by the sensors only for participants who are face-to-face. Key characteristics of interest include the distribution of degree and the frequency and duration of contacts and their variation in rural and urban areas. These will be stratified by age, gender, role, and day of the week. Expected results: Resultant data will inform on social contact patterns in rural and urban areas of a previously unstudied population. Ensuing data will be used to parameterize mathematical simulation models of transmission of a range of respiratory viruses, including respiratory syncytial virus, and used to explore the impact of intervention measures such as vaccination and social distancing.",2019 Aug 22,"['Kiti, Moses Chapa', 'Melegaro, Alessia', 'Cattuto, Ciro', 'Nokes, David James']",Wellcome Open Res,,,True
257c4916d1ec89f09d6d2b42b42042b6aeaa41bb,PMC,Clinical correlation of influenza and respiratory syncytial virus load measured by digital PCR,http://dx.doi.org/10.1371/journal.pone.0220908,PMC6720028,31479459,CC BY,"Acute respiratory tract infections are a major cause of respiratory morbidity and mortality in pediatric patients worldwide. However, accurate viral and immunologic markers to predict clinical outcomes of this patient population are still lacking. Droplet digital PCR assays for influenza and respiratory syncytial virus (RSV) were designed and performed in 64 respiratory samples from 23 patients with influenza virus infection and 73 samples from 19 patients with RSV infection. Samples of patients with hematologic malignancies, solid tumors, or sickle cell disease were included. Clinical information from institutional medical records was reviewed to assess disease severity. Samples from patients with fever or respiratory symptoms had a significantly higher viral loads than those from asymptomatic patients. Samples from patients with influenza virus and RSV infection collected at presentation had significantly higher viral loads than those collected from patients after completing a course of oseltamivir or ribavirin, respectively. RSV loads correlated positively with clinical symptoms in patients ≤5 years of age, whereas influenza viral loads were associated with clinical symptoms, irrespective of age. Patients receiving antivirals for influenza and RSV had a significant reduction in viral loads after completing therapy. Digital PCR offers an effective method to monitor the efficacy of antiviral treatment for respiratory tract infections in immunocompromised hosts.",2019 Sep 3,"['Hijano, Diego R.', 'Brazelton de Cardenas, Jessica', 'Maron, Gabriela', 'Garner, Cherilyn D.', 'Ferrolino, Jose A.', 'Dallas, Ronald H.', 'Gu, Zhengming', 'Hayden, Randall T.']",PLoS One,,,True
ecd6b92d6dd1c0baf31f1c8c86a6ee100d8e0b4d,PMC,Clinical correlation of influenza and respiratory syncytial virus load measured by digital PCR,http://dx.doi.org/10.1371/journal.pone.0220908,PMC6720028,31479459,CC BY,"Acute respiratory tract infections are a major cause of respiratory morbidity and mortality in pediatric patients worldwide. However, accurate viral and immunologic markers to predict clinical outcomes of this patient population are still lacking. Droplet digital PCR assays for influenza and respiratory syncytial virus (RSV) were designed and performed in 64 respiratory samples from 23 patients with influenza virus infection and 73 samples from 19 patients with RSV infection. Samples of patients with hematologic malignancies, solid tumors, or sickle cell disease were included. Clinical information from institutional medical records was reviewed to assess disease severity. Samples from patients with fever or respiratory symptoms had a significantly higher viral loads than those from asymptomatic patients. Samples from patients with influenza virus and RSV infection collected at presentation had significantly higher viral loads than those collected from patients after completing a course of oseltamivir or ribavirin, respectively. RSV loads correlated positively with clinical symptoms in patients ≤5 years of age, whereas influenza viral loads were associated with clinical symptoms, irrespective of age. Patients receiving antivirals for influenza and RSV had a significant reduction in viral loads after completing therapy. Digital PCR offers an effective method to monitor the efficacy of antiviral treatment for respiratory tract infections in immunocompromised hosts.",2019 Sep 3,"['Hijano, Diego R.', 'Brazelton de Cardenas, Jessica', 'Maron, Gabriela', 'Garner, Cherilyn D.', 'Ferrolino, Jose A.', 'Dallas, Ronald H.', 'Gu, Zhengming', 'Hayden, Randall T.']",PLoS One,,,True
2b532466bcad2dea4891e62bb86097a2089d95ec,PMC,Genetic and phylogenetic analyses of the first GIII.2 bovine norovirus in China,http://dx.doi.org/10.1186/s12917-019-2060-0,PMC6720400,31477115,CC BY,"BACKGROUND: Norovirus (NoV) is recognized as a highly contagious enteric pathogen of mammals, and bovine norovirus (BNoV) is associated with calf diarrhoea and has caused great economic losses in the cattle industry. RESULTS: Here, we describe a case of emerging calf diarrhoea on a cattle farm in Henan Province, Central China. BNoV was the only enteric pathogen detected in outbreaks according to tests for enteric viruses, bacteria and parasites. The complete genome of the newly identified strain CH-HNSC-2018 was successfully sequenced and found to be 7342 nucleotides in length. Sequence and phylogenetic analyses revealed that CH-HNSC-2018 belongs to GIII.2 BNoV. Further analysis of the major capsid protein demonstrated that it is separated by specific genetic distances from previous BNoV strains identified in China and has 4 new amino acid (aa) mutations, 134A, 327 T, 380 L and 423A, in the VP1 protein and 11 aa substitutions in the hypervariable P2 subdomain, suggesting that the BNoV strains circulating in China are diverse. CONCLUSIONS: This is the first detection of GIII.2 BNoV in the VP1 region in China. This report should form a basis for further molecular studies on NoV and bovine enteric viruses in China. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-019-2060-0) contains supplementary material, which is available to authorized users.",2019 Sep 2,"['Shi, Zhihai', 'Wang, Wenjia', 'Xu, Zhaoxue', 'Zhang, Xiaozhan', 'Lan, Yali']",BMC Vet Res,,,True
e3f168287dc3669b48862c0e70e000fc49edf00a,PMC,Blockade of EGFR Activation Promotes TNF-Induced Lung Epithelial Cell Apoptosis and Pulmonary Injury,http://dx.doi.org/10.3390/ijms20164021,PMC6720446,31426531,CC BY,"Pneumonitis is the leading cause of death associated with the use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) against non-small cell lung cancer (NSCLC). However, the risk factors and the mechanism underlying this toxicity have not been elucidated. Tumor necrosis factor (TNF) has been reported to transactivate EGFR in pulmonary epithelial cells. Hence, we aimed to test the hypothesis that EGFR tyrosine kinase activity regulates TNF-mediated bronchial epithelial cell survival, and that inhibition of EGFR activity increases TNF-induced lung epithelial cell apoptosis. We used surfactant protein C (SPC)-TNF transgenic (tg) mice which overexpress TNF in the lungs. In this model, gefitinib, an EGFR-TKI, enhanced lung epithelial cell apoptosis and lymphocytic inflammation, indicating that EGFR tyrosine kinase prevents TNF-induced lung injury. Furthermore, IL-17A was significantly upregulated by gefitinib in SPC-TNF tg mice and p38MAPK activation was observed, indicative of a pathway involved in lung epithelial cell apoptosis. Moreover, in lung epithelial cells, BEAS-2B, TNF stimulated EGFR transactivation via the TNF-α-converting enzyme in a manner that requires heparin binding (HB)-EGF and transforming growth factor (TGF)-α. These novel findings have significant implications in understanding the role of EGFR in maintaining human bronchial epithelial cell homeostasis and in NSCLC treatment.",2019 Aug 17,"['Yamaoka, Toshimitsu', 'Arata, Satoru', 'Homma, Mayumi', 'Homma, Tetsuya', 'Kusumoto, Sojiro', 'Ando, Koichi', 'Manabe, Ryou', 'Kishino, Yasunari', 'Ohba, Motoi', 'Tsurutani, Junji', 'Takimoto, Masafumi', 'Ohmori, Tohru', 'Sagara, Hironori']",Int J Mol Sci,,,True
41734f9087773eafddb2a6907b4075a3cb661a85,PMC,A descriptive analysis of the Spatio-temporal distribution of intestinal infectious diseases in China,http://dx.doi.org/10.1186/s12879-019-4400-x,PMC6721277,31477044,CC BY,"BACKGROUND: Intestinal infectious diseases (IIDs) have caused numerous deaths worldwide, particularly among children. In China, eight IIDs are listed as notifiable infectious diseases, including cholera, poliomyelitis, dysentery, typhoid and paratyphoid (TAP), viral Hepatitis A, viral Hepatitis E, hand-foot-mouth disease (HFMD) and other infectious diarrhoeal diseases (OIDDs). The aim of the study is to analyse the spatio-temporal distribution of IIDs from 2006 to 2016. METHODS: Data on the incidence of IIDs from 2006 to 2016 were collected from the public health science data centre issued by the Chinese Center for Disease Control and Prevention. This study applied seasonal decomposition analysis, spatial autocorrelation analysis and space-time scan analysis. Plots and maps were constructed to visualize the spatio-temporal distribution of IIDs. RESULTS: Regarding temporal analysis, the incidence of HFMD and Hepatitis E showed a distinct increasing trend, while the incidence of TAP, dysentery, and Hepatitis A presented decreasing trends over the last decade. The incidence of OIID remained steady. Summer is the season with the greatest number of cases of different IIDs. Regarding the spatial distribution, approximately all p values for the global Moran’s I from 2006 to 2016 were less than 0.05, indicating that the incidences of the epidemics were unevenly distributed throughout the country. The high-risk areas for HFMD and OIDD were located in the Beijing-Tianjin-Tangshan (BTT) region and south China. The high-risk areas for TAP were located in some parts of southwest China. A higher incidence rates for dysentery and Hepatitis A were observed in the BTT region and some west provincial units. The high-risk areas for Hepatitis E were the BTT region and the Yangtze River Delta area. CONCLUSIONS: Based on our temporal and spatial analysis of IIDs, we identified the high-risk periods and clusters of regions for the diseases. HFMD and OIDD exhibited high incidence rates, which reflected the negligence of Class C diseases by the government. At the same time, the incidence rate of Hepatitis E gradually surpassed Hepatitis A. The authorities should pay more attention to Class C diseases and Hepatitis E. Regardless of the various distribution patterns of IIDs, disease-specific, location-specific, and disease-combined interventions should be established. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-4400-x) contains supplementary material, which is available to authorized users.",2019 Sep 2,"['Mao, Ying', 'Zhang, Ning', 'Zhu, Bin', 'Liu, Jinlin', 'He, Rongxin']",BMC Infect Dis,,,True
1de4de4c1b8a4d3c18f20867febc8f4a2758dfd9,PMC,Nucleolar and Ribosomal DNA Structure under Stress: Yeast Lessons for Aging and Cancer,http://dx.doi.org/10.3390/cells8080779,PMC6721496,31357498,CC BY,"Once thought a mere ribosome factory, the nucleolus has been viewed in recent years as an extremely sensitive gauge of diverse cellular stresses. Emerging concepts in nucleolar biology include the nucleolar stress response (NSR), whereby a series of cell insults have a special impact on the nucleolus. These insults include, among others, ultra-violet radiation (UV), nutrient deprivation, hypoxia and thermal stress. While these stresses might influence nucleolar biology directly or indirectly, other perturbances whose origin resides in the nucleolar biology also trigger nucleolar and systemic stress responses. Among the latter, we find mutations in nucleolar and ribosomal proteins, ribosomal RNA (rRNA) processing inhibitors and ribosomal DNA (rDNA) transcription inhibition. The p53 protein also mediates NSR, leading ultimately to cell cycle arrest, apoptosis, senescence or differentiation. Hence, NSR is gaining importance in cancer biology. The nucleolar size and ribosome biogenesis, and how they connect with the Target of Rapamycin (TOR) signalling pathway, are also becoming important in the biology of aging and cancer. Simple model organisms like the budding yeast Saccharomyces cerevisiae, easy to manipulate genetically, are useful in order to study nucleolar and rDNA structure and their relationship with stress. In this review, we summarize the most important findings related to this topic.",2019 Jul 26,"['Matos-Perdomo, Emiliano', 'Machín, Félix']",Cells,,,True
6f402164832578c18fec0cc33d29c944acf81a26,PMC,Interplay between Intrinsic and Innate Immunity during HIV Infection,http://dx.doi.org/10.3390/cells8080922,PMC6721663,31426525,CC BY,"Restriction factors are antiviral components of intrinsic immunity which constitute a first line of defense by blocking different steps of the human immunodeficiency virus (HIV) replication cycle. In immune cells, HIV infection is also sensed by several pattern recognition receptors (PRRs), leading to type I interferon (IFN-I) and inflammatory cytokines production that upregulate antiviral interferon-stimulated genes (ISGs). Several studies suggest a link between these two types of immunity. Indeed, restriction factors, that are generally interferon-inducible, are able to modulate immune responses. This review highlights recent knowledge of the interplay between restriction factors and immunity inducing antiviral defenses. Counteraction of this intrinsic and innate immunity by HIV viral proteins will also be discussed.",2019 Aug 17,"['Bergantz, Louis', 'Subra, Frédéric', 'Deprez, Eric', 'Delelis, Olivier', 'Richetta, Clémence']",Cells,,,True
1eb822e2417937f3273c3423e25cd1344ba9a1e7,PMC,Endangered wild salmon infected by newly discovered viruses,http://dx.doi.org/10.7554/eLife.47615,PMC6721791,31478480,CC BY,"The collapse of iconic, keystone populations of sockeye (Oncorhynchus nerka) and Chinook (Oncorhynchus tshawytscha) salmon in the Northeast Pacific is of great concern. It is thought that infectious disease may contribute to declines, but little is known about viruses endemic to Pacific salmon. Metatranscriptomic sequencing and surveillance of dead and moribund cultured Chinook salmon revealed a novel arenavirus, reovirus and nidovirus. Sequencing revealed two different arenavirus variants which each infect wild Chinook and sockeye salmon. In situ hybridisation localised arenavirus mostly to blood cells. Population surveys of >6000 wild juvenile Chinook and sockeye salmon showed divergent distributions of viruses, implying different epidemiological processes. The discovery in dead and dying farmed salmon of previously unrecognised viruses that are also widely distributed in wild salmon, emphasizes the potential role that viral disease may play in the population dynamics of wild fish stocks, and the threat that these viruses may pose to aquaculture.",,"['Mordecai, Gideon J', 'Miller, Kristina M', 'Di Cicco, Emiliano', 'Schulze, Angela D', 'Kaukinen, Karia H', 'Ming, Tobi J', 'Li, Shaorong', 'Tabata, Amy', 'Teffer, Amy', 'Patterson, David A', 'Ferguson, Hugh W', 'Suttle, Curtis A']",eLife.; 8:e47615,,,True
644b4c7ff157be28bf0c216d2d6cb9edef3e1d4a,PMC,TRIM21—From Intracellular Immunity to Therapy,http://dx.doi.org/10.3389/fimmu.2019.02049,PMC6722209,31555278,CC BY,"Tripartite motif containing-21 (TRIM21) is a cytosolic ubiquitin ligase and antibody receptor that provides a last line of defense against invading viruses. It does so by acting as a sensor that intercepts antibody-coated viruses that have evaded extracellular neutralization and breached the cell membrane. Upon engagement of the Fc of antibodies bound to viruses, TRIM21 triggers a coordinated effector and signaling response that prevents viral replication while at the same time inducing an anti-viral cellular state. This dual effector function is tightly regulated by auto-ubiquitination and phosphorylation. Therapeutically, TRIM21 has been shown to be detrimental in adenovirus based gene therapy, while it may be favorably utilized to prevent tau aggregation in neurodegenerative disorders. In addition, TRIM21 may synergize with the complement system to block viral replication as well as transgene expression. TRIM21 can also be utilized as a research tool to deplete specific proteins in cells and zebrafish embryos. Here, we review our current biological understanding of TRIM21 in light of its versatile functions.",2019 Aug 28,"['Foss, Stian', 'Bottermann, Maria', 'Jonsson, Alexandra', 'Sandlie, Inger', 'James, Leo C.', 'Andersen, Jan Terje']",Front Immunol,,,True
50897189565f10bfa3b4884058b5a51cf75c091e,PMC,Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera,http://dx.doi.org/10.3390/v11080678,PMC6722596,31344850,CC BY,"Filovirus serological diagnosis and epidemiological investigations are hampered due to the unavailability of validated immunoassays. Diagnostic performance of three indirect enzyme-linked immunosorbent assays (I-ELISA) was evaluated for the detection of IgG antibody to Ebola virus (EBOV) in human sera. One I-ELISA was based on a whole EBOV antigen (WAg) and two utilized recombinant nucleocapsid (NP) and glycoproteins (GP), respectively. Validation data sets derived from individual sera collected in South Africa (SA), representing an EBOV non-endemic country, and from sera collected during an Ebola disease (EBOD) outbreak in Sierra Leone (SL), were categorized according to the compounded results of the three I-ELISAs and real time reverse-transcription polymerase chain reaction (RT-PCR). At the cut-off values selected at 95% accuracy level by the two-graph receiver operating characteristic analysis, specificity in the SA EBOV negative serum panel (n = 273) ranged from 98.17% (GP ELISA) to 99.27% (WAg ELISA). Diagnostic specificity in the SL EBOV negative panel (n = 676) was 100% by the three ELISAs. The diagnostic sensitivity in 423 RT-PCR confirmed EBOD patients was dependent on the time when the serum was collected after onset of disease. It significantly increased 2 weeks post-onset, reaching 100% sensitivity by WAg and NP and 98.1% by GP I-ELISA.",2019 Jul 24,"['Paweska, Janusz T.', 'Moolla, Naazneen', 'Storm, Nadia', 'Msimang, Veerle', 'Conteh, Ousman', 'Weyer, Jacqueline', 'van Vuren, Petrus Jansen']",Viruses,,,True
1803065327394f7f38931024cd4219d47f5f7d8b,PMC,Proteomics Computational Analyses Suggest that the Antennavirus Glycoprotein Complex Includes a Class I Viral Fusion Protein (α-Penetrene) with an Internal Zinc-Binding Domain and a Stable Signal Peptide,http://dx.doi.org/10.3390/v11080750,PMC6722660,31416162,CC BY,"A metatranscriptomic study of RNA viruses in cold-blooded vertebrates identified two related viruses from frogfish (Antennarius striatus) that represent a new genus Antennavirus in the family Arenaviridae (Order: Bunyavirales). Computational analyses were used to identify features common to class I viral fusion proteins (VFPs) in antennavirus glycoproteins, including an N-terminal fusion peptide, two extended alpha-helices, an intrahelical loop, and a carboxyl terminal transmembrane domain. Like mammarenavirus and hartmanivirus glycoproteins, the antennavirus glycoproteins have an intracellular zinc-binding domain and a long virion-associated stable signal peptide (SSP). The glycoproteins of reptarenaviruses are also class I VFPs, but do not contain zinc-binding domains nor do they encode SSPs. Divergent evolution from a common progenitor potentially explains similarities of antennavirus, mammarenavirus, and hartmanivirus glycoproteins, with an ancient recombination event resulting in a divergent reptarenavirus glycoprotein.",2019 Aug 14,"['Garry, Courtney E.', 'Garry, Robert F.']",Viruses,,,True
c4a57f04b093ea0da25ea63094e72d862f84a104,PMC,Proteomics Computational Analyses Suggest that the Antennavirus Glycoprotein Complex Includes a Class I Viral Fusion Protein (α-Penetrene) with an Internal Zinc-Binding Domain and a Stable Signal Peptide,http://dx.doi.org/10.3390/v11080750,PMC6722660,31416162,CC BY,"A metatranscriptomic study of RNA viruses in cold-blooded vertebrates identified two related viruses from frogfish (Antennarius striatus) that represent a new genus Antennavirus in the family Arenaviridae (Order: Bunyavirales). Computational analyses were used to identify features common to class I viral fusion proteins (VFPs) in antennavirus glycoproteins, including an N-terminal fusion peptide, two extended alpha-helices, an intrahelical loop, and a carboxyl terminal transmembrane domain. Like mammarenavirus and hartmanivirus glycoproteins, the antennavirus glycoproteins have an intracellular zinc-binding domain and a long virion-associated stable signal peptide (SSP). The glycoproteins of reptarenaviruses are also class I VFPs, but do not contain zinc-binding domains nor do they encode SSPs. Divergent evolution from a common progenitor potentially explains similarities of antennavirus, mammarenavirus, and hartmanivirus glycoproteins, with an ancient recombination event resulting in a divergent reptarenavirus glycoprotein.",2019 Aug 14,"['Garry, Courtney E.', 'Garry, Robert F.']",Viruses,,,False
7203ff6238ce039aad6fbcbceab04051a59ae0e2,PMC,Human Antimicrobial Peptides as Therapeutics for Viral Infections,http://dx.doi.org/10.3390/v11080704,PMC6722670,31374901,CC BY,"Successful in vivo infection following pathogen entry requires the evasion and subversion of multiple immunological barriers. Antimicrobial peptides (AMPs) are one of the first immune pathways upregulated during infection by multiple pathogens, in multiple organs in vivo. In humans, there are many classes of AMPs exhibiting broad antimicrobial activities, with defensins and the human cathelicidin LL-37 being the best studied examples. Whereas historically the efficacy and therapeutic potential of AMPs against bacterial infection has been the primary focus of research, recent studies have begun to elucidate the antiviral properties of AMPs as well as their role in regulation of inflammation and chemoattraction. AMPs as therapeutic tools seem especially promising against emerging infectious viral pathogens for which no approved vaccines or treatments are currently available, such as dengue virus (DENV) and Zika virus (ZIKV). In this review, we summarize recent studies elucidating the efficacy and diverse mechanisms of action of various classes of AMPs against multiple viral pathogens, as well as the potential use of human AMPs in novel antiviral therapeutic strategies.",2019 Aug 1,"['Ahmed, Aslaa', 'Siman-Tov, Gavriella', 'Hall, Grant', 'Bhalla, Nishank', 'Narayanan, Aarthi']",Viruses,,,True
5535ed240ab00c780ce2aa42f1fbe13ef24b9120,PMC,Reliable and Standardized Animal Models to Study the Pathogenesis of Bluetongue and Schmallenberg Viruses in Ruminant Natural Host Species with Special Emphasis on Placental Crossing,http://dx.doi.org/10.3390/v11080753,PMC6722754,31443153,CC BY,"Starting in 2006, bluetongue virus serotype 8 (BTV8) was responsible for a major epizootic in Western and Northern Europe. The magnitude and spread of the disease were surprisingly high and the control of BTV improved significantly with the marketing of BTV8 inactivated vaccines in 2008. During late summer of 2011, a first cluster of reduced milk yield, fever, and diarrhoea was reported in the Netherlands. Congenital malformations appeared in March 2012 and Schmallenberg virus (SBV) was identified, becoming one of the very few orthobunyaviruses distributed in Europe. At the start of both epizootics, little was known about the pathogenesis and epidemiology of these viruses in the European context and most assumptions were extrapolated based on other related viruses and/or other regions of the World. Standardized and repeatable models potentially mimicking clinical signs observed in the field are required to study the pathogenesis of these infections, and to clarify their ability to cross the placental barrier. This review presents some of the latest experimental designs for infectious disease challenges with BTV or SBV. Infectious doses, routes of infection, inoculum preparation, and origin are discussed. Particular emphasis is given to the placental crossing associated with these two viruses.",2019 Aug 15,"['Martinelle, Ludovic', 'Dal Pozzo, Fabiana', 'Thiry, Etienne', 'De Clercq, Kris', 'Saegerman, Claude']",Viruses,,,True
62c1b83631e0a74cb6f73b5c46460769271c21b2,PMC,Development of Protein- and Peptide-Based HIV Entry Inhibitors Targeting gp120 or gp41,http://dx.doi.org/10.3390/v11080705,PMC6722851,31374953,CC BY,"Application of highly active antiretroviral drugs (ARDs) effectively reduces morbidity and mortality in HIV-infected individuals. However, the emergence of multiple drug-resistant strains has led to the increased failure of ARDs, thus calling for the development of anti-HIV drugs with targets or mechanisms of action different from those of the current ARDs. The first peptide-based HIV entry inhibitor, enfuvirtide, was approved by the U.S. FDA in 2003 for treatment of HIV/AIDS patients who have failed to respond to the current ARDs, which has stimulated the development of several series of protein- and peptide-based HIV entry inhibitors in preclinical and clinical studies. In this review, we highlighted the properties and mechanisms of action for those promising protein- and peptide-based HIV entry inhibitors targeting the HIV-1 gp120 or gp41 and discussed their advantages and disadvantages, compared with the current ARDs.",2019 Aug 1,"['Pu, Jing', 'Wang, Qian', 'Xu, Wei', 'Lu, Lu', 'Jiang, Shibo']",Viruses,,,True
990adafb33c7402d0a1753fb05c351e6bf7fc80d,PMC,Viral Long-Term Evolutionary Strategies Favor Stability over Proliferation,http://dx.doi.org/10.3390/v11080677,PMC6722887,31344814,CC BY,"Viruses are known to have some of the highest and most diverse mutation rates found in any biological replicator, with single-stranded (ss) RNA viruses evolving the fastest, and double-stranded (ds) DNA viruses having rates approaching those of bacteria. As mutation rates are tightly and negatively correlated with genome size, selection is a clear driver of viral evolution. However, the role of intragenomic interactions as drivers of viral evolution is still unclear. To understand how these two processes affect the long-term evolution of viruses infecting humans, we comprehensively analyzed ssRNA, ssDNA, dsRNA, and dsDNA viruses, to find which virus types and which functions show evidence for episodic diversifying selection and correlated evolution. We show that selection mostly affects single stranded viruses, that correlated evolution is more prevalent in DNA viruses, and that both processes, taken independently, mostly affect viral replication. However, the genes that are jointly affected by both processes are involved in key aspects of their life cycle, favoring viral stability over proliferation. We further show that both evolutionary processes are intimately linked at the amino acid level, which suggests that it is the joint action of selection and correlated evolution, and not just selection, that shapes the evolutionary trajectories of viruses—and possibly of their epidemiological potential.",2019 Jul 24,"['Aris-Brosou, Stéphane', 'Parent, Louis', 'Ibeh, Neke']",Viruses,,,True
9247a24b8db536b515b9d549da1c7e383381e29c,PMC,Viral Long-Term Evolutionary Strategies Favor Stability over Proliferation,http://dx.doi.org/10.3390/v11080677,PMC6722887,31344814,CC BY,"Viruses are known to have some of the highest and most diverse mutation rates found in any biological replicator, with single-stranded (ss) RNA viruses evolving the fastest, and double-stranded (ds) DNA viruses having rates approaching those of bacteria. As mutation rates are tightly and negatively correlated with genome size, selection is a clear driver of viral evolution. However, the role of intragenomic interactions as drivers of viral evolution is still unclear. To understand how these two processes affect the long-term evolution of viruses infecting humans, we comprehensively analyzed ssRNA, ssDNA, dsRNA, and dsDNA viruses, to find which virus types and which functions show evidence for episodic diversifying selection and correlated evolution. We show that selection mostly affects single stranded viruses, that correlated evolution is more prevalent in DNA viruses, and that both processes, taken independently, mostly affect viral replication. However, the genes that are jointly affected by both processes are involved in key aspects of their life cycle, favoring viral stability over proliferation. We further show that both evolutionary processes are intimately linked at the amino acid level, which suggests that it is the joint action of selection and correlated evolution, and not just selection, that shapes the evolutionary trajectories of viruses—and possibly of their epidemiological potential.",2019 Jul 24,"['Aris-Brosou, Stéphane', 'Parent, Louis', 'Ibeh, Neke']",Viruses,,,False
8763c9240b22a0e841ddb6e7e9a22ef3a566e97e,PMC,Decreased Sensitivity of the Serological Detection of Feline Immunodeficiency Virus Infection Potentially Due to Imported Genetic Variants,http://dx.doi.org/10.3390/v11080697,PMC6722909,31370217,CC BY,"Feline immunodeficiency virus (FIV) is a lentivirus of domestic cats worldwide. Diagnosis usually relies on antibody screening by point-of-care tests (POCT), e.g., by enzyme-linked immunosorbent assays (ELISA), and confirmation using Western blot (WB). We increasingly observed ELISA-negative, WB-positive samples and aimed to substantiate these observations using 1194 serum/plasma samples collected from 1998 to 2019 primarily from FIV-suspect cats. While 441 samples tested positive and 375 tested negative by ELISA and WB, 81 samples had discordant results: 70 were false ELISA-negative (WB-positive) and 11 were false ELISA-positive (WB-negative); 297 ambiguous results were not analyzed further. The diagnostic sensitivity and specificity of the ELISA (82% and 91%, respectively) were lower than those reported in 1995 (98% and 97%, respectively). The diagnostic efficiency was reduced from 97% to 86%. False ELISA-negative samples originated mainly (54%) from Switzerland (1995: 0%). Sixty-four false ELISA-negative samples were available for POCT (SNAP(TM)/WITNESS(R)): five were POCT-positive. FIV RT-PCR was positive for two of these samples and was weakly positive for two ELISA- and POCT-negative samples. Low viral loads prohibited sequencing. Our results suggest that FIV diagnosis has become more challenging, probably due to increasing travel by cats and the introduction of new FIV isolates not recognized by screening assays.",2019 Jul 31,"['Frankenfeld, Julia', 'Meili, Theres', 'Meli, Marina L.', 'Riond, Barbara', 'Helfer-Hungerbuehler, A. Katrin', 'Bönzli, Eva', 'Pineroli, Benita', 'Hofmann-Lehmann, Regina']",Viruses,,,True
f442fd7cf9f7ab6a2939acae3d1eea548dafac20,PMC,Establishment of Primary Transgenic Human Airway Epithelial Cell Cultures to Study Respiratory Virus–Host Interactions,http://dx.doi.org/10.3390/v11080747,PMC6723040,31412613,CC BY,"Primary human airway epithelial cell (hAEC) cultures represent a universal platform to propagate respiratory viruses and characterize their host interactions in authentic target cells. To further elucidate specific interactions between human respiratory viruses and important host factors in the airway epithelium, it is important to make hAEC cultures amenable to genetic modification. However, the short and finite lifespan of primary cells in cell culture creates a bottleneck for the genetic modification of these cultures. In the current study, we show that the incorporation of the Rho-associated protein kinase (ROCK) inhibitor (Y-27632) during cell propagation extends the life span of primary human cells in vitro and thereby facilitates the incorporation of lentivirus-based expression systems. Using fluorescent reporters for fluorescence-activated cell sorting (FACS)-based sorting, we generated homogenously fluorescent hAEC cultures that differentiate normally after lentiviral transduction. As a proof-of-principle, we demonstrate that host gene expression can be modulated post-differentiation via inducible short hairpin (sh)RNA-mediated knockdown. Importantly, functional characterization of these transgenic hAEC cultures with exogenous poly (I:C), as a proxy for virus infection, demonstrates that such modifications do not influence the host innate immune response. Moreover, the propagation kinetics of both human coronavirus 229E (HCoV-229E) and human respiratory syncytial virus (hRSV) were not affected. Combined, these results validate our newly established protocol for the genetic modification of hAEC cultures, thereby unlocking a unique potential for detailed molecular characterization of virus–host interactions in human respiratory epithelium.",2019 Aug 13,"['Jonsdottir, Hulda R.', 'Marti, Sabrina', 'Geerts, Dirk', 'Rodriguez, Regulo', 'Thiel, Volker', 'Dijkman, Ronald']",Viruses,,,True
9e61bd6c5144017a9405d0c8bd84b09608eef00b,PMC,Tannins: Prospectives and Actual Industrial Applications,http://dx.doi.org/10.3390/biom9080344,PMC6723084,31387308,CC BY,"The origin of tannins, their historical evolution, their different types, and their applications are described. Old and established applications are described, as well as the future applications which are being developed at present and that promise to have an industrial impact in the future. The chemistry of some of these applications is discussed where it is essential to understand the tannins and their derivates role. The essential points of each application, their drawbacks, and their chance of industrial application are briefly discussed. The article presents historical applications of tannins, such as leather, or traditional medicine, and more recent applications.",2019 Aug 5,"Pizzi, Antonio",Biomolecules,,,True
22b6982820cdeb330dc2086ea69713f6e109a671,PMC,Recombinant Chimeric Transmissible Gastroenteritis Virus (TGEV)—Porcine Epidemic Diarrhea Virus (PEDV) Virus Provides Protection against Virulent PEDV,http://dx.doi.org/10.3390/v11080682,PMC6723174,31349683,CC BY,"Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus causing high morbidity and mortality in porcine herds worldwide. Although both inactivated and live attenuated vaccines have been extensively used, the emergence of highly virulent strains and the recurrent outbreaks even in vaccinated farms highlight the need of effective vaccines. Engineering of genetically defined live attenuated vaccines is a rational approach for novel vaccine development. In this line, we engineered an attenuated virus based on the transmissible gastroenteritis virus (TGEV) genome, expressing a chimeric spike protein from a virulent United States (US) PEDV strain. This virus (rTGEV-RS-SPEDV) was attenuated in highly-sensitive five-day-old piglets, as infected animals did not lose weight and none of them died. In addition, the virus caused very minor tissue damage compared with a virulent virus. The rTGEV-RS-SPEDV vaccine candidate was also attenuated in three-week-old animals that were used to evaluate the protection conferred by this virus, compared with the protection induced by infection with a virulent PEDV US strain (PEDV-NVSL). The rTGEV-RS-SPEDV virus protected against challenge with a virulent PEDV strain, reducing challenge virus titers in jejunum and leading to undetectable challenge virus RNA levels in feces. The rTGEV-RS-SPEDV virus induced a humoral immune response specific for PEDV, including neutralizing antibodies. Altogether, the data indicated that rTGEV-RS-SPEDV is a promising vaccine candidate against virulent PEDV infection.",2019 Jul 25,"['Pascual-Iglesias, Alejandro', 'Sanchez, Carlos M.', 'Penzes, Zoltan', 'Sola, Isabel', 'Enjuanes, Luis', 'Zuñiga, Sonia']",Viruses,,,True
54458ee775b72a18830ed116a31336638b909fa7,PMC,The Innate Antiviral Response in Animals: An Evolutionary Perspective from Flagellates to Humans,http://dx.doi.org/10.3390/v11080758,PMC6723221,31426357,CC BY,"Animal cells have evolved dedicated molecular systems for sensing and delivering a coordinated response to viral threats. Our understanding of these pathways is almost entirely defined by studies in humans or model organisms like mice, fruit flies and worms. However, new genomic and functional data from organisms such as sponges, anemones and mollusks are helping redefine our understanding of these immune systems and their evolution. In this review, we will discuss our current knowledge of the innate immune pathways involved in sensing, signaling and inducing genes to counter viral infections in vertebrate animals. We will then focus on some central conserved players of this response including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs) and cGAS-STING, attempting to put their evolution into perspective. To conclude, we will reflect on the arms race that exists between viruses and their animal hosts, illustrated by the dynamic evolution and diversification of innate immune pathways. These concepts are not only important to understand virus-host interactions in general but may also be relevant for the development of novel curative approaches against human disease.",2019 Aug 16,"['Majzoub, Karim', 'Wrensch, Florian', 'Baumert, Thomas F.']",Viruses,,,True
d5313a4142703e79978710a40320548a17eed201,PMC,Production of Recombinant EAV with Tagged Structural Protein Gp3 to Study Artervirus Minor Protein Localization in Infected Cells,http://dx.doi.org/10.3390/v11080735,PMC6723265,31404947,CC BY,"Equine arteritis virus (EAV) is a prototype member of the Arterivirus family, comprising important pathogens of domestic animals. Minor glycoproteins of Arteriviruses are responsible for virus entry and cellular tropism. The experimental methods for studying minor Arterivirus proteins are limited because of the lack of antibodies and nested open reading frames (ORFs). In this study, we generated recombinant EAV with separated ORFs 3 and 4, and Gp3 carrying HA-tag (Gp3-HA). The recombinant viruses were stable on passaging and replicated in titers similar to the wild-type EAV. Gp3-HA was incorporated into the virion particles as monomers and as a Gp2/Gp3-HA/Gp4 trimer. Gp3-HA localized in ER and, to a lesser extent, in the Golgi, it also co-localized with the E protein but not with the N protein. The co-localization of Gp3-HA and the E protein with ERGIC was reduced. Moreover, EAV with Gp3-HA could become a valuable research tool for identifying host cell factors during infection and the role of Gp3 in virus attachment and entry.",2019 Aug 9,"['Matczuk, Anna Karolina', 'Chodaczek, Grzegorz', 'Ugorski, Maciej']",Viruses,,,True
fb773634dcd17957e12be78e5c33ba753d82d3f5,PMC,Role of Glutathionylation in Infection and Inflammation,http://dx.doi.org/10.3390/nu11081952,PMC6723385,31434242,CC BY,"Glutathionylation, that is, the formation of mixed disulfides between protein cysteines and glutathione (GSH) cysteines, is a reversible post-translational modification catalyzed by different cellular oxidoreductases, by which the redox state of the cell modulates protein function. So far, most studies on the identification of glutathionylated proteins have focused on cellular proteins, including proteins involved in host response to infection, but there is a growing number of reports showing that microbial proteins also undergo glutathionylation, with modification of their characteristics and functions. In the present review, we highlight the signaling role of GSH through glutathionylation, particularly focusing on microbial (viral and bacterial) glutathionylated proteins (GSSPs) and host GSSPs involved in the immune/inflammatory response to infection; moreover, we discuss the biological role of the process in microbial infections and related host responses.",2019 Aug 20,"['Checconi, Paola', 'Limongi, Dolores', 'Baldelli, Sara', 'Ciriolo, Maria Rosa', 'Nencioni, Lucia', 'Palamara, Anna Teresa']",Nutrients,,,True
b4f6baab270ef953349d05c6f2936803c92bf4b4,PMC,Single Stranded DNA Viruses Associated with Capybara Faeces Sampled in Brazil,http://dx.doi.org/10.3390/v11080710,PMC6723397,31382446,CC BY,"Capybaras (Hydrochoerus hydrochaeris), the world’s largest rodents, are distributed throughout South America. These wild herbivores are commonly found near water bodies and are well adapted to rural and urban areas. There is limited information on the viruses circulating through capybaras. This study aimed to expand the knowledge on the viral diversity associated with capybaras by sampling their faeces. Using a viral metagenomics approach, we identified diverse single-stranded DNA viruses in the capybara faeces sampled in the Distrito Federal, Brazil. A total of 148 complete genomes of viruses in the Microviridae family were identified. In addition, 14 genomoviruses (family Genomoviridae), a novel cyclovirus (family Circoviridae), and a smacovirus (family Smacoviridae) were identified. Also, 37 diverse viruses that cannot be assigned to known families and more broadly referred to as unclassified circular replication associated protein encoding single-stranded (CRESS) DNA viruses were identified. This study provides a snapshot of the viral diversity associated with capybaras that may be infectious to these animals or associated with their microbiota or diet.",2019 Aug 2,"['Fontenele, Rafaela S.', 'Lacorte, Cristiano', 'Lamas, Natalia S.', 'Schmidlin, Kara', 'Varsani, Arvind', 'Ribeiro, Simone G.']",Viruses,,,True
7f3637433b7c8dff7fc35f0b5e67794877bce0c1,PMC,Camelid VHHs Fused to Human Fc Fragments Provide Long Term Protection Against Botulinum Neurotoxin A in Mice,http://dx.doi.org/10.3390/toxins11080464,PMC6723419,31394847,CC BY,"The bacterium Clostridium botulinum is the causative agent of botulism—a severe intoxication caused by botulinum neurotoxin (BoNT) and characterized by damage to the nervous system. In an effort to develop novel C. botulinum immunotherapeutics, camelid single-domain antibodies (sdAbs, VHHs, or nanobodies) could be used due to their unique structure and characteristics. In this study, VHHs were produced using phage display technology. A total of 15 different monoclonal VHHs were selected based on their comlementarity-determining region 3 (CDR3) sequences. Different toxin lethal dose (LD(50)) challenges with each selected phage clone were conducted in vivo to check their neutralizing potency. We demonstrated that modification of neutralizing VHHs with a human immunoglobulin G (IgG)1 Fc (fragment crystallizable) fragment (fusionbody, VHH-Fc) significantly increased the circulation time in the blood (up to 14 days). At the same time, VHH-Fc showed the protective activity 1000 times higher than monomeric form when challenged with 5 LD(50). Moreover, VHH-Fcs remained protective even 14 days after antibody administration. These results indicate that this VHH-Fc could be used as an effective long term antitoxin protection against botulinum type A.",2019 Aug 7,"['Godakova, Svetlana A.', 'Noskov, Anatoly N.', 'Vinogradova, Irina D.', 'Ugriumova, Galina A.', 'Solovyev, Andrey I.', 'Esmagambetov, Ilias B.', 'Tukhvatulin, Amir I.', 'Logunov, Denis Y.', 'Naroditsky, Boris S.', 'Shcheblyakov, Dmitry V.', 'Gintsburg, Aleksandr L.']",Toxins (Basel),,,True
00dce8da5fcee849b30c9d7a7e358c5855b14ca9,PMC,Viruses and Autoimmunity: A Review on the Potential Interaction and Molecular Mechanisms,http://dx.doi.org/10.3390/v11080762,PMC6723519,31430946,CC BY,"For a long time, viruses have been shown to modify the clinical picture of several autoimmune diseases, including type 1 diabetes (T1D), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren’s syndrome (SS), herpetic stromal keratitis (HSK), celiac disease (CD), and multiple sclerosis (MS). Best examples of viral infections that have been proposed to modulate the induction and development of autoimmune diseases are the infections with enteric viruses such as Coxsackie B virus (CVB) and rotavirus, as well as influenza A viruses (IAV), and herpesviruses. Other viruses that have been studied in this context include, measles, mumps, and rubella. Epidemiological studies in humans and experimental studies in animal have shown that viral infections can induce or protect from autoimmunopathologies depending on several factors including genetic background, host-elicited immune responses, type of virus strain, viral load, and the onset time of infection. Still, data delineating the clear mechanistic interaction between the virus and the immune system to induce autoreactivity are scarce. Available data indicate that viral-induced autoimmunity can be activated through multiple mechanisms including molecular mimicry, epitope spreading, bystander activation, and immortalization of infected B cells. Contrarily, the protective effects can be achieved via regulatory immune responses which lead to the suppression of autoimmune phenomena. Therefore, a better understanding of the immune-related molecular processes in virus-induced autoimmunity is warranted. Here we provide an overview of the current understanding of viral-induced autoimmunity and the mechanisms that are associated with this phenomenon.",2019 Aug 19,"['Smatti, Maria K.', 'Cyprian, Farhan S.', 'Nasrallah, Gheyath K.', 'Al Thani, Asmaa A.', 'Almishal, Ruba O.', 'Yassine, Hadi M.']",Viruses,,,True
03f315449023c980e42af7eb150d0cd9cab57f5a,PMC,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Dromedary Camels in Africa and Middle East,http://dx.doi.org/10.3390/v11080717,PMC6723520,31387326,CC BY,"Dromedary camels are the natural reservoirs of the Middle East respiratory syndrome coronavirus (MERS-CoV). Camels are mostly bred in East African countries then exported into Africa and Middle East for consumption. To understand the distribution of MERS-CoV among camels in North Africa and the Middle East, we conducted surveillance in Egypt, Senegal, Tunisia, Uganda, Jordan, Saudi Arabia, and Iraq. We also performed longitudinal studies of three camel herds in Egypt and Jordan to elucidate MERS-CoV infection and transmission. Between 2016 and 2018, a total of 4027 nasal swabs and 3267 serum samples were collected from all countries. Real- time PCR revealed that MERS-CoV RNA was detected in nasal swab samples from Egypt, Senegal, Tunisia, and Saudi Arabia. Microneutralization assay showed that antibodies were detected in all countries. Positive PCR samples were partially sequenced, and a phylogenetic tree was built. The tree suggested that all sequences are of clade C and sequences from camels in Egypt formed a separate group from previously published sequences. Longitudinal studies showed high seroprevalence in adult camels. These results indicate the widespread distribution of the virus in camels. A systematic active surveillance and longitudinal studies for MERS-CoV are needed to understand the epidemiology of the disease and dynamics of viral infection.",2019 Aug 5,"['Kandeil, Ahmed', 'Gomaa, Mokhtar', 'Nageh, Ahmed', 'Shehata, Mahmoud M.', 'Kayed, Ahmed E.', 'Sabir, Jamal S. M.', 'Abiadh, Awatef', 'Jrijer, Jamel', 'Amr, Zuhair', 'Abi Said, Mounir', 'Byarugaba, Denis K.', 'Wabwire-Mangen, Fred', 'Tugume, Titus', 'Mohamed, Nadira S.', 'Attar, Roba', 'Hassan, Sabah M.', 'Abdulaziz Linjawi, Sabah', 'Moatassim, Yassmin', 'Kutkat, Omnia', 'Mahmoud, Sara', 'Bagato, Ola', 'Abo Shama, Noura M.', 'El-Shesheny, Rabeh', 'Mostafa, Ahmed', 'A. P. M. Perera, Ranawaka', 'K. W. Chu, Daniel', 'Hassan, Nagla', 'Elsokary, Basma', 'Saad, Ahmed', 'Sobhy, Heba', 'El Masry, Ihab', 'P. McKenzie, Pamela', 'J. Webby, Richard', 'Peiris, Malik', 'J. Makonnen, Yilma', 'A. Ali, Mohamed', 'Kayali, Ghazi']",Viruses,,,True
a3032ce8a80f772cc9150de358b980aa489cd924,PMC,Flexible HIV-1 Biosensor Based on the Au/MoS(2) Nanoparticles/Au Nanolayer on the PET Substrate,http://dx.doi.org/10.3390/nano9081076,PMC6723525,31357466,CC BY,"An electrochemical flexible biosensor composed of gold (Au), molybdenum disulfide nanoparticles (MoS(2) NPs), and Au (Au/MoS(2)/Au nanolayer) on the polyethylene terephthalate (PET) substrate is developed to detect envelope glycoprotein GP120 (gp120), the surface protein of HIV-1. To fabricate the nanolayer on the PET substrate, Au is sputter coated on the flexible PET substrate and MoS(2) NPs are spin coated on Au, which is sputter coated once again with Au. The gp120 antibody is then immobilized on this flexible electrode through cysteamine (Cys) modified on the surface of the Au/MoS(2)/Au nanolayer. Fabrication of the biosensor is verified by atomic force microscopy, scanning electron microscopy, and cyclic voltammetry. A flexibility test is done using a micro-fatigue tester. Detection of the gp120 is measured by square wave voltammetry. The results indicate that the prepared biosensor detects 0.1 pg/mL of gp120, which is comparable with previously reported gp120 biosensors prepared even without flexibility. Therefore, the proposed biosensor supports the development of a nanomaterial-based flexible sensing platform for highly sensitive biosensors with flexibility for wearable device application.",2019 Jul 26,"['Shin, Minkyu', 'Yoon, Jinho', 'Yi, Chanyong', 'Lee, Taek', 'Choi, Jeong-Woo']",Nanomaterials (Basel),,,True
dd517d505a1ec8b3109e1038c0d9eca7cc370355,PMC,Flexible HIV-1 Biosensor Based on the Au/MoS(2) Nanoparticles/Au Nanolayer on the PET Substrate,http://dx.doi.org/10.3390/nano9081076,PMC6723525,31357466,CC BY,"An electrochemical flexible biosensor composed of gold (Au), molybdenum disulfide nanoparticles (MoS(2) NPs), and Au (Au/MoS(2)/Au nanolayer) on the polyethylene terephthalate (PET) substrate is developed to detect envelope glycoprotein GP120 (gp120), the surface protein of HIV-1. To fabricate the nanolayer on the PET substrate, Au is sputter coated on the flexible PET substrate and MoS(2) NPs are spin coated on Au, which is sputter coated once again with Au. The gp120 antibody is then immobilized on this flexible electrode through cysteamine (Cys) modified on the surface of the Au/MoS(2)/Au nanolayer. Fabrication of the biosensor is verified by atomic force microscopy, scanning electron microscopy, and cyclic voltammetry. A flexibility test is done using a micro-fatigue tester. Detection of the gp120 is measured by square wave voltammetry. The results indicate that the prepared biosensor detects 0.1 pg/mL of gp120, which is comparable with previously reported gp120 biosensors prepared even without flexibility. Therefore, the proposed biosensor supports the development of a nanomaterial-based flexible sensing platform for highly sensitive biosensors with flexibility for wearable device application.",2019 Jul 26,"['Shin, Minkyu', 'Yoon, Jinho', 'Yi, Chanyong', 'Lee, Taek', 'Choi, Jeong-Woo']",Nanomaterials (Basel),,,False
4cbde00704ec55e2d030ca4f8ecb73da6ba959ee,PMC,Serological Screening for Coronavirus Infections in Cats,http://dx.doi.org/10.3390/v11080743,PMC6723642,31412572,CC BY,"Coronaviruses (CoVs) are widespread among mammals and birds and known for their potential for cross-species transmission. In cats, infections with feline coronaviruses (FCoVs) are common. Several non-feline coronaviruses have been reported to infect feline cells as well as cats after experimental infection, supported by their ability to engage the feline receptor ortholog for cell entry. However, whether cats might become naturally infected with CoVs of other species is unknown. We analyzed coronavirus infections in cats by serological monitoring. In total 137 cat serum samples and 25 FCoV type 1 or type 2-specific antisera were screened for the presence of antibodies against the S1 receptor binding subunit of the CoV spike protein, which is immunogenic and possesses low amino acid sequence identity among coronavirus species. Seventy-eight sera were positive for antibodies that recognized one or more coronavirus S1s whereas 1 serum exclusively reacted with human coronavirus 229E (HCoV-229E) and two sera exclusively reacted with porcine delta coronavirus (PDCoV). We observed antigenic cross-reactivity between S1s of type 1 and type 2 FCoVs, and between FCoV type 1 and porcine epidemic diarrhea virus (PEDV). Domain mapping of antibody epitopes indicated the presence of conserved epitope(s) particularly in the CD domains of S1. The cross-reactivity of FCoV type 1 and PEDV was also observed at the level of virus neutralization. To conclude, we provide the first evidence of antigenic cross-reactivity among S1 proteins of coronaviruses, which should be considered in the development of serological diagnoses. In addition, the potential role of cats in cross-species transmission of coronaviruses cannot be excluded.",2019 Aug 13,"['Zhao, Shan', 'Li, Wentao', 'Schuurman, Nancy', 'van Kuppeveld, Frank', 'Bosch, Berend-Jan', 'Egberink, Herman']",Viruses,,,True
b1753e4a0beec1c8e54c2c3bc8073c27ca841310,PMC,Serological Screening for Coronavirus Infections in Cats,http://dx.doi.org/10.3390/v11080743,PMC6723642,31412572,CC BY,"Coronaviruses (CoVs) are widespread among mammals and birds and known for their potential for cross-species transmission. In cats, infections with feline coronaviruses (FCoVs) are common. Several non-feline coronaviruses have been reported to infect feline cells as well as cats after experimental infection, supported by their ability to engage the feline receptor ortholog for cell entry. However, whether cats might become naturally infected with CoVs of other species is unknown. We analyzed coronavirus infections in cats by serological monitoring. In total 137 cat serum samples and 25 FCoV type 1 or type 2-specific antisera were screened for the presence of antibodies against the S1 receptor binding subunit of the CoV spike protein, which is immunogenic and possesses low amino acid sequence identity among coronavirus species. Seventy-eight sera were positive for antibodies that recognized one or more coronavirus S1s whereas 1 serum exclusively reacted with human coronavirus 229E (HCoV-229E) and two sera exclusively reacted with porcine delta coronavirus (PDCoV). We observed antigenic cross-reactivity between S1s of type 1 and type 2 FCoVs, and between FCoV type 1 and porcine epidemic diarrhea virus (PEDV). Domain mapping of antibody epitopes indicated the presence of conserved epitope(s) particularly in the CD domains of S1. The cross-reactivity of FCoV type 1 and PEDV was also observed at the level of virus neutralization. To conclude, we provide the first evidence of antigenic cross-reactivity among S1 proteins of coronaviruses, which should be considered in the development of serological diagnoses. In addition, the potential role of cats in cross-species transmission of coronaviruses cannot be excluded.",2019 Aug 13,"['Zhao, Shan', 'Li, Wentao', 'Schuurman, Nancy', 'van Kuppeveld, Frank', 'Bosch, Berend-Jan', 'Egberink, Herman']",Viruses,,,False
ace038ad5c62cabf0d49f6b8cc9aa0ee6f39a656,PMC,Hepatitis E Virus Replication,http://dx.doi.org/10.3390/v11080719,PMC6723718,31390784,CC BY,"Hepatitis E virus (HEV) is a small quasi-enveloped, (+)-sense, single-stranded RNA virus belonging to the Hepeviridae family. There are at least 20 million HEV infections annually and 60,000 HEV-related deaths worldwide. HEV can cause up to 30% mortality in pregnant women and progress to liver cirrhosis in immunocompromised individuals and is, therefore, a greatly underestimated public health concern. Although a prophylactic vaccine for HEV has been developed, it is only licensed in China, and there is currently no effective, non-teratogenic treatment. HEV encodes three open reading frames (ORFs). ORF1 is the largest viral gene product, encoding the replicative machinery of the virus including a methyltransferase, RNA helicase, and an RNA-dependent RNA polymerase. ORF1 additionally contains a number of poorly understood domains including a hypervariable region, a putative protease, and the so-called ‘X’ and ‘Y’ domains. ORF2 is the viral capsid essential for formation of infectious particles and ORF3 is a small protein essential for viral release. In this review, we focus on the domains encoded by ORF1, which collectively mediate the virus’ asymmetric genome replication strategy. We summarize what is known, unknown, and hotly debated regarding the coding and non-coding regions of HEV ORF1, and present a model of how HEV replicates its genome.",2019 Aug 6,"['LeDesma, Robert', 'Nimgaonkar, Ila', 'Ploss, Alexander']",Viruses,,,True
d710e993d5c0aca81ed537d9462953a234309a1c,PMC,Mannose-Specific Lectins from Marine Algae: Diverse Structural Scaffolds Associated to Common Virucidal and Anti-Cancer Properties,http://dx.doi.org/10.3390/md17080440,PMC6723950,31357490,CC BY,"To date, a number of mannose-specific lectins have been isolated and characterized from seaweeds, especially from red algae. In fact, man-specific seaweed lectins consist of different structural scaffolds harboring a single or a few carbohydrate-binding sites which specifically recognize mannose-containing glycans. Depending on the structural scaffold, man-specific seaweed lectins belong to five distinct structurally-related lectin families, namely (1) the griffithsin lectin family (β-prism I scaffold); (2) the Oscillatoria agardhii agglutinin homolog (OAAH) lectin family (β-barrel scaffold); (3) the legume lectin-like lectin family (β-sandwich scaffold); (4) the Galanthus nivalis agglutinin (GNA)-like lectin family (β-prism II scaffold); and, (5) the MFP2-like lectin family (MFP2-like scaffold). Another algal lectin from Ulva pertusa, has been inferred to the methanol dehydrogenase related lectin family, because it displays a rather different GlcNAc-specificity. In spite of these structural discrepancies, all members from the five lectin families share a common ability to specifically recognize man-containing glycans and, especially, high-mannose type glycans. Because of their mannose-binding specificity, these lectins have been used as valuable tools for deciphering and characterizing the complex mannose-containing glycans from the glycocalyx covering both normal and transformed cells, and as diagnostic tools and therapeutic drugs that specifically recognize the altered high-mannose N-glycans occurring at the surface of various cancer cells. In addition to these anti-cancer properties, man-specific seaweed lectins have been widely used as potent human immunodeficiency virus (HIV-1)-inactivating proteins, due to their capacity to specifically interact with the envelope glycoprotein gp120 and prevent the virion infectivity of HIV-1 towards the host CD4+ T-lymphocyte cells in vitro.",2019 Jul 26,"['Barre, Annick', 'Simplicien, Mathias', 'Benoist, Hervé', 'Van Damme, Els J.M.', 'Rougé, Pierre']",Mar Drugs,,,True
8b1ef7f0f343414329cefb9a014bffcf3f92f117,PMC,Metagenomic Next-Generation Sequencing Reveal Presence of a Novel Ungulate Bocaparvovirus in Alpacas,http://dx.doi.org/10.3390/v11080701,PMC6724020,31370351,CC BY,"Viruses belonging to the genus Bocaparvovirus (BoV) are a genetically diverse group of DNA viruses known to cause respiratory, enteric, and neurological diseases in animals, including humans. An intestinal sample from an alpaca (Vicugna pacos) herd with reoccurring diarrhea and respiratory disease was submitted for next-generation sequencing, revealing the presence of a BoV strain. The alpaca BoV strain (AlBoV) had a 58.58% whole genome nucleotide percent identity to a camel BoV from Dubai, belonging to a tentative ungulate BoV 8 species (UBoV8). Recombination events were lacking with other UBoV strains. The AlBoV genome was comprised of the NS1, NP1, and VP1 proteins. The NS1 protein had the highest amino acid percent identity range (57.89–67.85%) to the members of UBoV8, which was below the 85% cut-off set by the International Committee on Taxonomy of Viruses. The low NS1 amino acid identity suggests that AlBoV is a tentative new species. The whole genome, NS1, NP1, and VP1 phylogenetic trees illustrated distinct branching of AlBoV, sharing a common ancestor with UBoV8. Walker loop and Phospholipase A2 (PLA2) motifs that are vital for virus infectivity were identified in NS1 and VP1 proteins, respectively. Our study reports a novel BoV strain in an alpaca intestinal sample and highlights the need for additional BoV research.",2019 Jul 31,"['Kumar, Deepak', 'Chaudhary, Suman', 'Lu, Nanyan', 'Duff, Michael', 'Heffel, Mathew', 'McKinney, Caroline A.', 'Bedenice, Daniela', 'Marthaler, Douglas']",Viruses,,,True
436164085d9fd52ea5d7ebed65465e0a41495c04,PMC,Inhibitory Effects of Antiviral Drug Candidates on Canine Parvovirus in F81 cells,http://dx.doi.org/10.3390/v11080742,PMC6724046,31412574,CC BY,"Canine parvovirus (CPV) is a common etiological agent of acute enteritis, which occurs globally in domestic and wild carnivores. Despite the widespread use of inactivated or live attenuated vaccines, the emergence of antigenic variants and the influence of maternal antibodies have raised some concerns regarding the efficacy of commercial vaccines. While no specific antiviral therapy for CPV infection exists, the only treatment option for the infection is supportive therapy based on symptoms. Thus, there is an urgent medical need to develop antiviral therapeutic options to reduce the burden of CPV-related disease. In this study, a cytopathic effect (CPE)-based high-throughput screening assay was used to screen CPV inhibitors from a Food and Drug Administration (FDA)-approved drug library. After two rounds of screening, seven out of 1430 screened drugs were found to have >50% CPE inhibition. Three drugs—Nitazoxanide, Closantel Sodium, and Closantel—with higher anti-CPV effects were further evaluated in F81 cells by absolute PCR quantification and indirect immunofluorescence assay (IFA). The inhibitory effects of all three drugs were dose-dependent. Time of addition assay indicated that the drugs inhibited the early processes of the CPV replication cycle, and the inhibition effects were relatively high within 2 h postinfection. Western blot assay also showed that the three drugs had broad-spectrum antiviral activity against different subspecies of three CPV variants. In addition, antiapoptotic effects were observed within 12 h in Nitazoxanide-treated F81 cells regardless of CPV infection, while Closantel Sodium- or Closantel-treated cells had no pro- or antiapoptotic effects. In conclusion, Nitazoxanide, Closantel Sodium, and Closantel can effectively inhibit different subspecies of CPV. Since the safety profiles of FDA-approved drugs have already been extensively studied, these three drugs can potentially become specific and effective anti-CPV drugs.",2019 Aug 13,"['Zhou, Hongzhuan', 'Su, Xia', 'Lin, Lulu', 'Zhang, Jin', 'Qi, Qi', 'Guo, Fangfang', 'Xu, Fuzhou', 'Yang, Bing']",Viruses,,,True
6098edec4684d70f8ed441589507f186aa7f7874,PMC,Inhibitory Effects of Antiviral Drug Candidates on Canine Parvovirus in F81 cells,http://dx.doi.org/10.3390/v11080742,PMC6724046,31412574,CC BY,"Canine parvovirus (CPV) is a common etiological agent of acute enteritis, which occurs globally in domestic and wild carnivores. Despite the widespread use of inactivated or live attenuated vaccines, the emergence of antigenic variants and the influence of maternal antibodies have raised some concerns regarding the efficacy of commercial vaccines. While no specific antiviral therapy for CPV infection exists, the only treatment option for the infection is supportive therapy based on symptoms. Thus, there is an urgent medical need to develop antiviral therapeutic options to reduce the burden of CPV-related disease. In this study, a cytopathic effect (CPE)-based high-throughput screening assay was used to screen CPV inhibitors from a Food and Drug Administration (FDA)-approved drug library. After two rounds of screening, seven out of 1430 screened drugs were found to have >50% CPE inhibition. Three drugs—Nitazoxanide, Closantel Sodium, and Closantel—with higher anti-CPV effects were further evaluated in F81 cells by absolute PCR quantification and indirect immunofluorescence assay (IFA). The inhibitory effects of all three drugs were dose-dependent. Time of addition assay indicated that the drugs inhibited the early processes of the CPV replication cycle, and the inhibition effects were relatively high within 2 h postinfection. Western blot assay also showed that the three drugs had broad-spectrum antiviral activity against different subspecies of three CPV variants. In addition, antiapoptotic effects were observed within 12 h in Nitazoxanide-treated F81 cells regardless of CPV infection, while Closantel Sodium- or Closantel-treated cells had no pro- or antiapoptotic effects. In conclusion, Nitazoxanide, Closantel Sodium, and Closantel can effectively inhibit different subspecies of CPV. Since the safety profiles of FDA-approved drugs have already been extensively studied, these three drugs can potentially become specific and effective anti-CPV drugs.",2019 Aug 13,"['Zhou, Hongzhuan', 'Su, Xia', 'Lin, Lulu', 'Zhang, Jin', 'Qi, Qi', 'Guo, Fangfang', 'Xu, Fuzhou', 'Yang, Bing']",Viruses,,,False
e1aadb0d868db77c282d5ce3f8f85508f8dabc4a,PMC,Preparedness and management of global public health threats at points of entry in Ireland and the EU in the context of a potential Brexit,http://dx.doi.org/10.1186/s12992-019-0496-4,PMC6724249,31481126,CC BY,"Health security in the European Union (EU) aims to protect citizens from serious threats to health such as biological agents and infectious disease outbreaks- whether natural, intentional or accidental. Threats may include established infections, emerging diseases or chemical and radiological agents. Co-ordinated international efforts attempt to minimize risks and mitigate the spread of infectious disease across borders. We review the current situation (March 2019) with respect to detection and management of serious human health threats across Irish borders- and what may change for Ireland if/when the United Kingdom (UK) withdraws from the EU (Brexit). Specifically, this paper reviews international legislation covering health threats, and its national transposition; and EU legislation and processes, especially the relevant European Decision No. 1082/2013/EU of the European Parliament and of the Council on serious cross border threats to health with repeal of Decision No 2119/98/EC. We enumerate European surveillance systems and agencies which relate to port health security; we consider consortia and academic arrangements within the EU framework and established collaboration with the World Health Organization. We describe current Health Services Executive port health structures in Ireland which address preparedness and management of human health threats at points of entry. We appraise risks which Brexit could bring, reviewing literature on shared concerns about these risks, and we evaluate post-Brexit challenges for the EU, and potential opportunities to remain within current structures in shared health threat preparedness and response. It is imperative that the UK, Ireland and the EU work together to mitigate these risks using some agreed joint coordination mechanisms for a robust, harmonised approach to global public health threats at points of entry.",2019 Sep 3,"['Boland, Máirín', 'O’Riordan, Mary']",Global Health,,,True
009892e02bc1a4c9abf6f547b979e68ecbde8087,PMC,Viral respiratory tract infections in young children with cystic fibrosis: a prospective full-year seasonal study,http://dx.doi.org/10.1186/s12985-019-1208-7,PMC6724274,31481063,CC BY,"BACKGROUND: Viral respiratory tract infections are common during early childhood. How they impact cystic fibrosis lung disease history in young children is poorly known. The principal aim of our study was to determinate respiratory tract infections frequency in this cystic fibrosis young population. Secondary outcomes were nature of viral agents recovered and impact of such infections. METHODS: We conducted a prospective cohort study of 25 children affected by cystic fibrosis and aged less than 2 years. Nasal samplings were taken systematically monthly or bimonthly with additional samples taken during respiratory tract infections episodes. Ten pathogens were tested by a combination of five duplex RT-PCRs or PCRs: influenza A and B, respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus/enterovirus (RV/EV)), coronavirus (HKU1, NL63, 229E and OC43), parainfluenza virus (1–4), adenovirus and bocavirus (Respiratory Multi-Well System MWS r-gene®, BioMérieux, Marcy l’Étoile, France). Cycle thresholds (CTs) were reported for all positive samples and considered positive for values below 40. Quantitative variables were compared using a nonparametric statistical test (Wilcoxon signed rank for paired comparisons). Pearson’s correlation coefficient (r) was used to assess relationships between two variables. Statistical analyses were performed using SAS v9.4 (SAS Institute, Cary, NC, USA) or GraphPad Prism V6.00 (GraphPad Software, La Jolla, CA, USA). The significance level was set at 0.05. RESULTS: The mean age at inclusion was 9.6 ± 6.7 months. The patients had 3.4 ± 1.7 respiratory tract infections episodes per child per year. Forty-four respiratory tract infections (69%) were associated with virus: rhinovirus and enterovirus (RV/EV) were implied in 61% of them and respiratory syncytial virus (RSV) in 14%. Only one patient required hospitalization for lower respiratory tract infections. 86% of the patients were treated by antibiotics for a mean of 13.8 ± 6.2 days. RSV infections (n = 6) were usually of mild severity. CONCLUSIONS: Respiratory tract infections in young children with cystic fibrosis were of mild severity, rarely requiring hospitalization. Unsurprisingly, RV/EV were the most frequent agents. RSV-related morbidity seems low in this population. This raises the question of the usefulness of RSV preventive medication in this young population.",2019 Sep 3,"['Eymery, Mathilde', 'Morfin, Florence', 'Doleans-Jordheim, Anne', 'Perceval, Marie', 'Ohlmann, Camille', 'Mainguy, Catherine', 'Reix, Philippe']",Virol J,,,True
58072613e14774fd4f9bfc63ee4b2d6ef78811ac,PMC,"Lessons from an active surveillance pilot to assess the pneumonia of unknown etiology surveillance system in China, 2016: the need to increase clinician participation in the detection and reporting of emerging respiratory infectious diseases",http://dx.doi.org/10.1186/s12879-019-4345-0,PMC6724368,31481020,CC BY,"BACKGROUND: We sought to assess reporting in China’s Pneumonia of Unknown Etiology (PUE) passive surveillance system for emerging respiratory infections and to identify ways to improve the PUE surveillance system’s detection of respiratory infections of public health significance. METHODS: From February 29–May 29, 2016, we actively identified and enrolled patients in two hospitals with acute respiratory infections (ARI) that met all PUE case criteria. We reviewed medical records for documented exposure history associated with respiratory infectious diseases, collected throat samples that were tested for seasonal and avian influenza, and interviewed clinicians regarding reasons for reporting or not reporting PUE cases. We described and analyzed the proportion of PUE cases reported and clinician awareness of and practices related to the PUE system. RESULTS: Of 2619 ARI admissions in two hospitals, 335(13%) met the PUE case definition; none were reported. Of 311 specimens tested, 18(6%) were seasonal influenza virus-positive; none were avian influenza-positive. < 10% PUE case medical records documented whether or not there were exposures to animals or others with respiratory illness. Most commonly cited reasons for not reporting cases were no awareness of the PUE system (76%) and not understanding the case definition (53%). CONCLUSIONS: Most clinicians have limited awareness of and are not reporting to the PUE system. Exposures related to respiratory infections are rarely documented in medical records. Increasing clinicians’ awareness of the PUE system and including relevant exposure items in standard medical records may increase reporting. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-4345-0) contains supplementary material, which is available to authorized users.",2019 Sep 3,"['Xiang, Nijuan', 'Song, Ying', 'Wang, Yu', 'Wu, Jiabing', 'Millman, Alexander J.', 'Greene, Carolyn M.', 'Ding, Zhentao', 'Sun, Jie', 'Yang, Wei', 'Guo, Guoxia', 'Wang, Ruirui', 'Guo, Ping', 'Ren, Zhixing', 'Gong, Lei', 'Xu, Pengpeng', 'Zhou, Suizan', 'Lin, Dan', 'Ni, Daxin', 'Feng, Zijian', 'Li, Qun']",BMC Infect Dis,,,True
ed993511b5e81e2086d1e5ac97c6719521a2952c,PMC,Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study,http://dx.doi.org/10.1016/S0140-6736(19)30721-4,PMC6727070,31257127,CC BY,"BACKGROUND: Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. METHODS: We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1–59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. FINDINGS: Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6–97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3–65·6) of causes, whereas bacteria accounted for 27·3% (23·3–31·6) and Mycobacterium tuberculosis for 5·9% (3·9–8·3). Viruses were less common (54·5%, 95% CrI 47·4–61·5 vs 68·0%, 62·7–72·7) and bacteria more common (33·7%, 27·2–40·8 vs 22·8%, 18·3–27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4–34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus–enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. INTERPRETATION: In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. FUNDING: Bill & Melinda Gates Foundation.",2019 Aug 31,,Lancet,,,False
2dfc0df5fefbe3bd657f73f9c78b3d3278d8b20b,PMC,Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study,http://dx.doi.org/10.1016/S0140-6736(19)30721-4,PMC6727070,31257127,CC BY,"BACKGROUND: Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. METHODS: We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1–59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. FINDINGS: Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6–97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3–65·6) of causes, whereas bacteria accounted for 27·3% (23·3–31·6) and Mycobacterium tuberculosis for 5·9% (3·9–8·3). Viruses were less common (54·5%, 95% CrI 47·4–61·5 vs 68·0%, 62·7–72·7) and bacteria more common (33·7%, 27·2–40·8 vs 22·8%, 18·3–27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4–34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus–enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. INTERPRETATION: In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. FUNDING: Bill & Melinda Gates Foundation.",2019 Aug 31,,Lancet,,,False
ab9240ebae17608f688ebee1fea34fff47003ef0,PMC,A snapshot of pneumonia research activity and collaboration patterns (2001–2015): a global bibliometric analysis,http://dx.doi.org/10.1186/s12874-019-0819-4,PMC6727334,31488065,CC BY,"BACKGROUND: This article describes a bibliometric review of the scientific production, geographical distribution, collaboration, impact, and subject area focus of pneumonia research indexed on the Web of Science over a 15-year period. METHODS: We searched the Web of Science database using the Medical Subject Heading (MeSH) of “Pneumonia” from January 1, 2001 to December 31, 2015. The only document types we studied were original articles and reviews, analyzing descriptive indicators by five-year periods and the scientific production by country, adjusting for population, economic, and research-related parameters. RESULTS: A total of 22,694 references were retrieved. The number of publications increased steadily over time, from 981 publications in 2001 to 1977 in 2015 (R(2) = 0.956). The most productive country was the USA (38.49%), followed by the UK (7.18%) and Japan (5.46%). Research production from China increased by more than 1000%. By geographical area, North America (42.08%) and Europe (40.79%) were most dominant. Scientific production in low- and middle-income countries more than tripled, although their overall contribution to the field remained limited (< 15%). Overall, 18.8% of papers were the result of an international collaboration, although this proportion was much higher in sub-Saharan Africa (46.08%) and South Asia (23.43%). According to the specific MeSH terms used, articles focused mainly on “Pneumonia, Bacterial” (19.99%), followed by “Pneumonia, Pneumococcal” (7.02%) and “Pneumonia, Ventilator-Associated” (6.79%). CONCLUSIONS: Pneumonia research increased steadily over the 15-year study period, with Europe and North America leading scientific production. About a fifth of all papers reflected international collaborations, and these were most evident in papers from sub-Saharan Africa and South Asia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12874-019-0819-4) contains supplementary material, which is available to authorized users.",2019 Sep 5,"['Ramos-Rincón, José M.', 'Pinargote-Celorio, Héctor', 'Belinchón-Romero, Isabel', 'González-Alcaide, Gregorio']",BMC Med Res Methodol,,,True
a0797dceb80b7f1c136590f3ba4b16da218de23f,PMC,Intracellular human antibody fragments recognizing the VP35 protein of Zaire Ebola filovirus inhibit the protein activity,http://dx.doi.org/10.1186/s12896-019-0554-2,PMC6727353,31488108,CC BY,"BACKGROUND: Ebola hemorrhagic fever is caused by the Ebola filovirus (EBOV), which is one of the most aggressive infectious agents known worldwide. The EBOV pathogenesis starts with uncontrolled viral replication and subversion of both the innate and adaptive host immune response. The multifunctional viral VP35 protein is involved in this process by exerting an antagonistic action against the early antiviral alpha/beta interferon (IFN-α/β) response, and represents a suitable target for the development of strategies to control EBOV infection. Phage display technology permits to select antibodies as single chain Fragment variable (scFv) from an artificial immune system, due to their ability to specifically recognize the antigen of interest. ScFv is ideal for genetic manipulation and to obtain antibody constructs useful for targeting either antigens expressed on cell surface or intracellular antigens if the scFv is expressed as intracellular antibody (intrabody) or delivered into the cells. RESULTS: Monoclonal antibodies (mAb) in scFv format specific for the EBOV VP35 were isolated from the ETH-2 library of human recombinant antibodies by phage display technology. Five different clones were identified by sequencing, produced in E.coli and expressed in CHO mammalian cells to be characterized in vitro. All the selected scFvs were able to react with recombinant VP35 protein in ELISA, one of the scFvs being also able to react in Western Blot assay (WB). In addition, all scFvs were expressed in cell cytoplasm as intrabodies; a luciferase reporter gene inhibition assay performed in A549 cells showed that two of the scFvs can significantly hamper the inhibition of the IFN-β-induced RIG-I signaling cascade mediated by EBOV VP35. CONCLUSION: Five antibodies in scFv format recognize an active form of EBOV VP35 in ELISA, while one antibody also recognizes VP35 in WB. Two of these scFvs were also able to interfere with the intracellular activity of VP35 in a cell system in vitro. These findings suggest that such antibodies in scFv format might be employed to develop therapeutic molecules able to hamper EBOV infections.",2019 Sep 5,"['Flego, Michela', 'Frau, Aldo', 'Accardi, Luisa', 'Mallano, Alessandra', 'Ascione, Alessandro', 'Gellini, Mara', 'Fanunza, Elisa', 'Vella, Stefano', 'Di Bonito, Paola', 'Tramontano, Enzo']",BMC Biotechnol,,,True
bc64088b806d6f43c4888ddb00a0479c8e57d33e,PMC,"Dynamic profiles, biodistribution and integration evaluation after intramuscular/intravenous delivery of a novel therapeutic DNA vaccine encoding chicken type II collagen for rheumatoid arthritis in vaccinated normal rodent",http://dx.doi.org/10.1186/s12951-019-0528-5,PMC6729025,31492169,CC BY,"BACKGROUND: The persistence, biodistribution, and risk of integration into the host genome of any new therapeutic DNA vaccine must be established in preclinical studies. We previously developed the DNA vaccine pcDNA-CCOL2A1 encoding chicken type II collagen (CCII) for the treatment of rheumatoid arthritis (RA). In the present study, we characterized its dynamic profile, biodistribution, and potential for genomic DNA integration in normal vaccinated rodent. RESULTS: A real-time quantitative PCR analysis (RT-qPCR) of animals administered a single dose of pcDNA-CCOL2A1 (300 μg/kg by intramuscular injection) showed that CCOL2A1 mRNA level in the blood peaked between 2 and 6 h post-immunization and then rapidly declined, and was undetectable between day 1–42. CCOL2A1 transcript was detected at the muscle injection site on days 3–14 post-immunization. Starting from day 14, the transcript was detected in the heart, liver, lung, and kidney but not in the spleen or thymus, and was expressed only in the lung on day 28. There was no CCOL2A1 mRNA present in the testes or ovaries at any time point. Non-invasive in vivo fluorescence imaging revealed CCII protein expression from 2 h up to day 10 and from 2 h up to day 35 after administration of pcDNA-CCOL2A1 via the intravenous and intramuscular routes, respectively; the protein had disappeared by day 42. Importantly, CCOL2A1 was not integrated into the host genome. CONCLUSIONS: These results indicate that pcDNA-CCOL2A1 vaccine is rapidly cleared within a short period of time and is therefore safe, and merits further development as a therapeutic vaccine for RA treatment.",2019 Sep 6,"['Zhao, Xiao', 'Long, Juan', 'Liang, Fei', 'Liu, Nan', 'Sun, Yuying', 'Xi, Yongzhi']",J Nanobiotechnology,,,True
ab49a01b79f3623438ca5e7f5833d95ef1701a55,PMC,A novel method to rescue and culture duck Astrovirus type 1 in vitro,http://dx.doi.org/10.1186/s12985-019-1218-5,PMC6729042,31488178,CC BY,"BACKGROUND: Reverse genetics systems enable the manipulation of viral genomes and therefore serve as robust reverse genetic tools to study RNA viruses. A DNA-launched rescue system initiates the transcription of viral genomic cDNA from eukaryotic promoter in transfected cells, generating homogenous RNA transcripts in vitro and thus enhancing virus rescue efficiency. As one of the hazardous pathogens to ducklings, the current knowledge of the pathogenesis of duck astrovirus type 1 (DAstV-1) is limited. The construction of a DNA-launched rescue system can help to accelerate the study of the virus pathogenesis. However, there is no report of such a system for DAstV-1. METHODS: In this study, a DNA-launched infectious clone of DAstV-1 was constructed from a cDNA plasmid, which contains a viral cDNA sequence flanked by hammerhead ribozyme (HamRz) and a hepatitis delta virus ribozyme (HdvRz) sequence at both terminals of the viral genome. A silent nucleotide mutation creating a Bgl II site in the ORF2 gene was made to distinguish the rescued virus (rDAstV-1) from the parental virus (pDAstV-1). Immunofluorescence assay (IFA) and western blot were conducted for rescued virus identification in duck embryo fibroblast (DEF) cells pre-treated with trypsin. The growth characteristics of rDAstV-1 and pDAstV-1 in DEF cells and the tissue tropism in 2-day-old ducklings of rDAstV-1 and pDAstV-1 were determined. RESULTS: The infectious DAstV-1 was successfully rescued from baby hamster kidney (BHK-21) cells and could propagate in DEF cells pre-treated with 1 μg/ml trypsin. Upon infection of DEF cells pre-treated with trypsin, DAstV-1 mRNA copies were identified after serial passaging, and the result showed that rDAstV-1 and pDAstV-1 shared similar replication kinetics. Animal experiment showed that the rDAstV-1 had an extensive tissue tropism, and the virus was capable of invading both the central and the peripheral immune organs in infected ducklings. CONCLUSIONS: An improved DNA-launched reverse genetics system for DAstV-1 was firstly constructed. Infectious virus recovered from BHK-21 cells could propagate in DEF cells pre-treated with trypsin. This is the first report of the successful in vitro cultivation of DAstV-1. We believe this valuable experimental system will contribute to the further study of DAstV-1 genome function and pathogenesis.",2019 Sep 5,"['Zhang, Ruihua', 'Lan, Jingjing', 'Li, Haie', 'Chen, Junhao', 'Yang, Yupeng', 'Lin, Shaoli', 'Xie, Zhijing', 'Jiang, Shijin']",Virol J,,,True
f80a73f77c3831a921a232122099f8aa5798dfd2,PMC,Possible roles of monocytes/macrophages in response to elephant endotheliotropic herpesvirus (EEHV) infections in Asian elephants (Elephas maximus),http://dx.doi.org/10.1371/journal.pone.0222158,PMC6730851,31491031,CC BY,"Elephant endotheliotropic herpesvirus-hemorrhagic disease (EEHV-HD) is the primary cause of acute, highly fatal, hemorrhagic diseases in young Asian elephants. Although monocytopenia is frequently observed in EEHV-HD cases, the role monocytes play in EEHV-disease pathogenesis is unknown. This study seeks to explain the responses of monocytes/macrophages in the pathogenesis of EEHV-HD. Samples of blood, frozen tissues, and formalin-fixed, paraffin-embedded (FFPE) tissues from EEHV1A-HD, EEHV4-HD, co-infected EEHV1A and 4-HD, and EEHV-negative calves were analyzed. Peripheral blood mononuclear cells (PBMCs) from the persistent EEHV4-infected and EEHV-negative calves were also studied. The results showed increased infiltration of Iba-1-positive macrophages in the inflamed tissues of the internal organs of elephant calves with EEHV-HD. In addition, cellular apoptosis also increased in the tissues of elephants with EEHV-HD, especially in the PBMCs, compared to the EEHV-negative control. In the PBMCs of persistent EEHV4-infected elephants, cytokine mRNA expression was high, particularly up-regulation of TNF-α and IFN-γ. Moreover, viral particles were observed in the cytoplasm of the persistent EEHV4-infected elephant monocytes. Our study demonstrated for the first time that apoptosis of the PBMCs increased in cases of EEHV-HD. Furthermore, this study showed that monocytes may serve as a vehicle for viral dissemination during EEHV infection in Asian elephants.",2019 Sep 6,"['Srivorakul, Saralee', 'Guntawang, Thunyamas', 'Kochagul, Varankpicha', 'Photichai, Kornravee', 'Sittisak, Tidaratt', 'Janyamethakul, Thittaya', 'Boonprasert, Khajohnpat', 'Khammesri, Siripat', 'Langkaphin, Warangkhana', 'Punyapornwithaya, Veerasak', 'Chuammitri, Phongsakorn', 'Thitaram, Chatchote', 'Pringproa, Kidsadagon']",PLoS One,,,True
39ea21a9a44d95523eac412e17ffaafc04b72bf4,PMC,"Patterns of seasonal and pandemic influenza-associated health care and mortality in Ontario, Canada",http://dx.doi.org/10.1186/s12889-019-7369-x,PMC6731609,31492122,CC BY,"BACKGROUND: Mathematical and statistical models are used to project the future time course of infectious disease epidemics and the expected future burden on health care systems and economies. Influenza is a particularly important disease in this context because it causes annual epidemics and occasional pandemics. In order to forecast health care utilization during epidemics—and the effects of hospitalizations and deaths on the contact network and, in turn, on transmission dynamics—modellers must make assumptions about the lengths of time between infection, visiting a physician, being admitted to hospital, leaving hospital, and death. More reliable forecasts could be be made if the distributions of times between these types of events (“delay distributions”) were known. METHODS: We estimated delay distributions in the province of Ontario, Canada, between 2006 and 2010. To do so, we used encrypted health insurance numbers to link 1.34 billion health care billing records to 4.27 million hospital inpatient stays. Because the four year period we studied included three typical influenza seasons and the 2009 influenza pandemic, we were able to compare the delay distributions in non-pandemic and pandemic settings. We also estimated conditional probabilities such as the probability of hospitalization within the year if diagnosed with influenza. RESULTS: In non-pandemic [pandemic] years, delay distribution medians (inter-quartile ranges) were: Service to Admission 6.3 days (0.1–17.6 days) [2.4 days (-0.3–13.6 days)], Admission to Discharge 3 days (1.4–5.9 days) [2.6 days (1.2–5.1 days)], Admission to Death 5.3 days (2.1–11 days) [6 days (2.6–13.1 days)]. (Service date is defined as the date, within the year, of the first health care billing that included a diagnostic code for influenza-like-illness.) Among individuals diagnosed with either pneumonia or influenza in a given year, 19% [16%] were hospitalized within the year and 3% [2%] died in hospital. Among all individuals who were hospitalized, 10% [12%] were diagnosed with pneumonia or influenza during the year and 5% [5%] died in hospital. CONCLUSION: Our empirical delay distributions and conditional probabilities should help facilitate more accurate forecasts in the future, including improved predictions of hospital bed demands during influenza outbreaks, and the expected effects of hospitalizations on epidemic dynamics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-019-7369-x) contains supplementary material, which is available to authorized users.",2019 Sep 6,"['Li, Michael', 'Bolker, Benjamin M.', 'Dushoff, Jonathan', 'Ma, Junling', 'Earn, David J.D.']",BMC Public Health,,,False
183e393843de9d6c653897f1039ad10af9750347,PMC,"Patterns of seasonal and pandemic influenza-associated health care and mortality in Ontario, Canada",http://dx.doi.org/10.1186/s12889-019-7369-x,PMC6731609,31492122,CC BY,"BACKGROUND: Mathematical and statistical models are used to project the future time course of infectious disease epidemics and the expected future burden on health care systems and economies. Influenza is a particularly important disease in this context because it causes annual epidemics and occasional pandemics. In order to forecast health care utilization during epidemics—and the effects of hospitalizations and deaths on the contact network and, in turn, on transmission dynamics—modellers must make assumptions about the lengths of time between infection, visiting a physician, being admitted to hospital, leaving hospital, and death. More reliable forecasts could be be made if the distributions of times between these types of events (“delay distributions”) were known. METHODS: We estimated delay distributions in the province of Ontario, Canada, between 2006 and 2010. To do so, we used encrypted health insurance numbers to link 1.34 billion health care billing records to 4.27 million hospital inpatient stays. Because the four year period we studied included three typical influenza seasons and the 2009 influenza pandemic, we were able to compare the delay distributions in non-pandemic and pandemic settings. We also estimated conditional probabilities such as the probability of hospitalization within the year if diagnosed with influenza. RESULTS: In non-pandemic [pandemic] years, delay distribution medians (inter-quartile ranges) were: Service to Admission 6.3 days (0.1–17.6 days) [2.4 days (-0.3–13.6 days)], Admission to Discharge 3 days (1.4–5.9 days) [2.6 days (1.2–5.1 days)], Admission to Death 5.3 days (2.1–11 days) [6 days (2.6–13.1 days)]. (Service date is defined as the date, within the year, of the first health care billing that included a diagnostic code for influenza-like-illness.) Among individuals diagnosed with either pneumonia or influenza in a given year, 19% [16%] were hospitalized within the year and 3% [2%] died in hospital. Among all individuals who were hospitalized, 10% [12%] were diagnosed with pneumonia or influenza during the year and 5% [5%] died in hospital. CONCLUSION: Our empirical delay distributions and conditional probabilities should help facilitate more accurate forecasts in the future, including improved predictions of hospital bed demands during influenza outbreaks, and the expected effects of hospitalizations on epidemic dynamics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-019-7369-x) contains supplementary material, which is available to authorized users.",2019 Sep 6,"['Li, Michael', 'Bolker, Benjamin M.', 'Dushoff, Jonathan', 'Ma, Junling', 'Earn, David J.D.']",BMC Public Health,,,True
fa9bac7dff2df0d1a276e95abf099e35e5c9f87f,PMC,A versatile platform technology for recombinant vaccines using non-propagative human parainfluenza virus type 2 vector,http://dx.doi.org/10.1038/s41598-019-49579-y,PMC6733870,31501502,CC BY,"Ectopic protein with proper steric structure was efficiently loaded onto the envelope of the F gene-defective BC-PIV vector derived from human parainfluenza virus type 2 (hPIV2) by a reverse genetics method of recombinant virus production. Further, ectopic antigenic peptide was successfully loaded either outside, inside, or at both sides of the envelope of the vector. The BC-PIV vector harboring the Ebola virus GP gene was able to elicit neutralizing antibodies in mice. In addition, BC-PIV with antigenic epitopes of both melanoma gp100 and WT1 tumor antigen induced a CD8+ T-cell-mediated response in tumor-transplanted syngeneic mice. Considering the low pathogenicity and recurrent infections of parental hPIV2, BC-PIV can be used as a versatile vector with high safety for recombinant vaccine development, addressing unmet medical needs.",2019 Sep 9,"['Ohtsuka, Junpei', 'Fukumura, Masayuki', 'Furuyama, Wakako', 'Wang, Shujie', 'Hara, Kenichiro', 'Maeda, Mitsuyo', 'Tsurudome, Masato', 'Miyamoto, Hiroko', 'Kaito, Aika', 'Tsuda, Nobuyuki', 'Kataoka, Yosky', 'Mizoguchi, Akira', 'Takada, Ayato', 'Nosaka, Tetsuya']",Sci Rep,,,False
e8fa6ff57f5e18b27fa9d70df3d3c90f4633264d,PMC,A versatile platform technology for recombinant vaccines using non-propagative human parainfluenza virus type 2 vector,http://dx.doi.org/10.1038/s41598-019-49579-y,PMC6733870,31501502,CC BY,"Ectopic protein with proper steric structure was efficiently loaded onto the envelope of the F gene-defective BC-PIV vector derived from human parainfluenza virus type 2 (hPIV2) by a reverse genetics method of recombinant virus production. Further, ectopic antigenic peptide was successfully loaded either outside, inside, or at both sides of the envelope of the vector. The BC-PIV vector harboring the Ebola virus GP gene was able to elicit neutralizing antibodies in mice. In addition, BC-PIV with antigenic epitopes of both melanoma gp100 and WT1 tumor antigen induced a CD8+ T-cell-mediated response in tumor-transplanted syngeneic mice. Considering the low pathogenicity and recurrent infections of parental hPIV2, BC-PIV can be used as a versatile vector with high safety for recombinant vaccine development, addressing unmet medical needs.",2019 Sep 9,"['Ohtsuka, Junpei', 'Fukumura, Masayuki', 'Furuyama, Wakako', 'Wang, Shujie', 'Hara, Kenichiro', 'Maeda, Mitsuyo', 'Tsurudome, Masato', 'Miyamoto, Hiroko', 'Kaito, Aika', 'Tsuda, Nobuyuki', 'Kataoka, Yosky', 'Mizoguchi, Akira', 'Takada, Ayato', 'Nosaka, Tetsuya']",Sci Rep,,,True
2f32fb8cf3cf8e48df1d344dbdd9dd86a00605cd,PMC,Dominant role of splenic marginal zone lipid rafts in the classical complement pathway against S. pneumoniae,http://dx.doi.org/10.1038/s41420-019-0213-3,PMC6733876,31531231,CC BY,"Lipid rafts (LRs) play crucial roles in complex physiological processes, modulating innate and acquired immune responses to pathogens. The transmembrane C-type lectins human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and its mouse homolog SIGN-R1 are distributed in LRs and expressed on splenic marginal zone (MZ) macrophages. The DC-SIGN-C1q or SIGN-R1-C1q complex could mediate the immunoglobulin (Ig)-independent classical complement pathway against Streptococcus pneumoniae. Precise roles of LRs during this complement pathway are unknown. Here we show that LRs are indispensable for accelerating the DC-SIGN- or SIGN-R1-mediated classical complement pathway against S. pneumoniae, thus facilitating rapid clearance of the pathogen. The trimolecular complex of SIGN-R1-C1q-C4 was exclusively enriched in LRs of splenic MZ macrophages and their localization was essential for activating C3 catabolism and enhancing pneumococcal clearance, which were abolished in SIGN-R1-knockout mice. However, DC-SIGN replacement on splenic MZ macrophage’s LRs of SIGN-R1-depleted mice reversed these defects. Disruption of LRs dramatically reduced pneumococcal uptake and decomposition. Additionally, DC- SIGN, C1q, C4, and C3 were obviously distributed in splenic LRs of cadavers. Therefore, LRs on splenic SIGN-R1(+) or DC-SIGN(+) macrophages could provide spatially confined and optimal bidirectional platforms, not only for usual intracellular events, for example recognition and phagocytosis of pathogens, but also an unusual extracellular event such as the complement system. These findings improve our understanding of the orchestrated roles of the spleen, unraveling a new innate immune system initiated from splenic MZ LRs, and yielding answers to several long-standing problems, including the need to understand the profound role of LRs in innate immunity, the need to identify how such a small portion of splenic SIGN-R1(+) macrophages (<0.05% of splenic macrophages) effectively resist S. pneumoniae, and the need to understand how LRs can promote the protective function of DC-SIGN against S. pneumoniae in the human spleen.",2019 Sep 9,"['Yang, Seung Woo', 'Park, Jin-Yeon', 'Choi, Hyeongjwa', 'Yun, Tae Jin', 'Choi, Woo-Sung', 'Kim, Min-Kyung', 'Lee, Yun Kyung', 'Park, Min', 'Jin, Yihwa', 'Joo, Jin Soo', 'Choi, In-Soo', 'Park, Seung Hwa', 'Hwang, Han Sung', 'Kang, Young-Sun']",Cell Death Discov,,,True
d93a081bd3bd9718521a76ebf008c776beed4b8d,PMC,Dominant role of splenic marginal zone lipid rafts in the classical complement pathway against S. pneumoniae,http://dx.doi.org/10.1038/s41420-019-0213-3,PMC6733876,31531231,CC BY,"Lipid rafts (LRs) play crucial roles in complex physiological processes, modulating innate and acquired immune responses to pathogens. The transmembrane C-type lectins human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and its mouse homolog SIGN-R1 are distributed in LRs and expressed on splenic marginal zone (MZ) macrophages. The DC-SIGN-C1q or SIGN-R1-C1q complex could mediate the immunoglobulin (Ig)-independent classical complement pathway against Streptococcus pneumoniae. Precise roles of LRs during this complement pathway are unknown. Here we show that LRs are indispensable for accelerating the DC-SIGN- or SIGN-R1-mediated classical complement pathway against S. pneumoniae, thus facilitating rapid clearance of the pathogen. The trimolecular complex of SIGN-R1-C1q-C4 was exclusively enriched in LRs of splenic MZ macrophages and their localization was essential for activating C3 catabolism and enhancing pneumococcal clearance, which were abolished in SIGN-R1-knockout mice. However, DC-SIGN replacement on splenic MZ macrophage’s LRs of SIGN-R1-depleted mice reversed these defects. Disruption of LRs dramatically reduced pneumococcal uptake and decomposition. Additionally, DC- SIGN, C1q, C4, and C3 were obviously distributed in splenic LRs of cadavers. Therefore, LRs on splenic SIGN-R1(+) or DC-SIGN(+) macrophages could provide spatially confined and optimal bidirectional platforms, not only for usual intracellular events, for example recognition and phagocytosis of pathogens, but also an unusual extracellular event such as the complement system. These findings improve our understanding of the orchestrated roles of the spleen, unraveling a new innate immune system initiated from splenic MZ LRs, and yielding answers to several long-standing problems, including the need to understand the profound role of LRs in innate immunity, the need to identify how such a small portion of splenic SIGN-R1(+) macrophages (<0.05% of splenic macrophages) effectively resist S. pneumoniae, and the need to understand how LRs can promote the protective function of DC-SIGN against S. pneumoniae in the human spleen.",2019 Sep 9,"['Yang, Seung Woo', 'Park, Jin-Yeon', 'Choi, Hyeongjwa', 'Yun, Tae Jin', 'Choi, Woo-Sung', 'Kim, Min-Kyung', 'Lee, Yun Kyung', 'Park, Min', 'Jin, Yihwa', 'Joo, Jin Soo', 'Choi, In-Soo', 'Park, Seung Hwa', 'Hwang, Han Sung', 'Kang, Young-Sun']",Cell Death Discov,,,False
f84758aa6a1b1e42de9bafd939315b9695b76bcf,PMC,Dominant role of splenic marginal zone lipid rafts in the classical complement pathway against S. pneumoniae,http://dx.doi.org/10.1038/s41420-019-0213-3,PMC6733876,31531231,CC BY,"Lipid rafts (LRs) play crucial roles in complex physiological processes, modulating innate and acquired immune responses to pathogens. The transmembrane C-type lectins human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and its mouse homolog SIGN-R1 are distributed in LRs and expressed on splenic marginal zone (MZ) macrophages. The DC-SIGN-C1q or SIGN-R1-C1q complex could mediate the immunoglobulin (Ig)-independent classical complement pathway against Streptococcus pneumoniae. Precise roles of LRs during this complement pathway are unknown. Here we show that LRs are indispensable for accelerating the DC-SIGN- or SIGN-R1-mediated classical complement pathway against S. pneumoniae, thus facilitating rapid clearance of the pathogen. The trimolecular complex of SIGN-R1-C1q-C4 was exclusively enriched in LRs of splenic MZ macrophages and their localization was essential for activating C3 catabolism and enhancing pneumococcal clearance, which were abolished in SIGN-R1-knockout mice. However, DC-SIGN replacement on splenic MZ macrophage’s LRs of SIGN-R1-depleted mice reversed these defects. Disruption of LRs dramatically reduced pneumococcal uptake and decomposition. Additionally, DC- SIGN, C1q, C4, and C3 were obviously distributed in splenic LRs of cadavers. Therefore, LRs on splenic SIGN-R1(+) or DC-SIGN(+) macrophages could provide spatially confined and optimal bidirectional platforms, not only for usual intracellular events, for example recognition and phagocytosis of pathogens, but also an unusual extracellular event such as the complement system. These findings improve our understanding of the orchestrated roles of the spleen, unraveling a new innate immune system initiated from splenic MZ LRs, and yielding answers to several long-standing problems, including the need to understand the profound role of LRs in innate immunity, the need to identify how such a small portion of splenic SIGN-R1(+) macrophages (<0.05% of splenic macrophages) effectively resist S. pneumoniae, and the need to understand how LRs can promote the protective function of DC-SIGN against S. pneumoniae in the human spleen.",2019 Sep 9,"['Yang, Seung Woo', 'Park, Jin-Yeon', 'Choi, Hyeongjwa', 'Yun, Tae Jin', 'Choi, Woo-Sung', 'Kim, Min-Kyung', 'Lee, Yun Kyung', 'Park, Min', 'Jin, Yihwa', 'Joo, Jin Soo', 'Choi, In-Soo', 'Park, Seung Hwa', 'Hwang, Han Sung', 'Kang, Young-Sun']",Cell Death Discov,,,False
1ee231435b5c7636ca5cca30617617256bdadaa7,PMC,Dominant role of splenic marginal zone lipid rafts in the classical complement pathway against S. pneumoniae,http://dx.doi.org/10.1038/s41420-019-0213-3,PMC6733876,31531231,CC BY,"Lipid rafts (LRs) play crucial roles in complex physiological processes, modulating innate and acquired immune responses to pathogens. The transmembrane C-type lectins human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and its mouse homolog SIGN-R1 are distributed in LRs and expressed on splenic marginal zone (MZ) macrophages. The DC-SIGN-C1q or SIGN-R1-C1q complex could mediate the immunoglobulin (Ig)-independent classical complement pathway against Streptococcus pneumoniae. Precise roles of LRs during this complement pathway are unknown. Here we show that LRs are indispensable for accelerating the DC-SIGN- or SIGN-R1-mediated classical complement pathway against S. pneumoniae, thus facilitating rapid clearance of the pathogen. The trimolecular complex of SIGN-R1-C1q-C4 was exclusively enriched in LRs of splenic MZ macrophages and their localization was essential for activating C3 catabolism and enhancing pneumococcal clearance, which were abolished in SIGN-R1-knockout mice. However, DC-SIGN replacement on splenic MZ macrophage’s LRs of SIGN-R1-depleted mice reversed these defects. Disruption of LRs dramatically reduced pneumococcal uptake and decomposition. Additionally, DC- SIGN, C1q, C4, and C3 were obviously distributed in splenic LRs of cadavers. Therefore, LRs on splenic SIGN-R1(+) or DC-SIGN(+) macrophages could provide spatially confined and optimal bidirectional platforms, not only for usual intracellular events, for example recognition and phagocytosis of pathogens, but also an unusual extracellular event such as the complement system. These findings improve our understanding of the orchestrated roles of the spleen, unraveling a new innate immune system initiated from splenic MZ LRs, and yielding answers to several long-standing problems, including the need to understand the profound role of LRs in innate immunity, the need to identify how such a small portion of splenic SIGN-R1(+) macrophages (<0.05% of splenic macrophages) effectively resist S. pneumoniae, and the need to understand how LRs can promote the protective function of DC-SIGN against S. pneumoniae in the human spleen.",2019 Sep 9,"['Yang, Seung Woo', 'Park, Jin-Yeon', 'Choi, Hyeongjwa', 'Yun, Tae Jin', 'Choi, Woo-Sung', 'Kim, Min-Kyung', 'Lee, Yun Kyung', 'Park, Min', 'Jin, Yihwa', 'Joo, Jin Soo', 'Choi, In-Soo', 'Park, Seung Hwa', 'Hwang, Han Sung', 'Kang, Young-Sun']",Cell Death Discov,,,False
e8e87fa9b8aa95055058ca519e923906fb8f30b9,PMC,Dominant role of splenic marginal zone lipid rafts in the classical complement pathway against S. pneumoniae,http://dx.doi.org/10.1038/s41420-019-0213-3,PMC6733876,31531231,CC BY,"Lipid rafts (LRs) play crucial roles in complex physiological processes, modulating innate and acquired immune responses to pathogens. The transmembrane C-type lectins human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and its mouse homolog SIGN-R1 are distributed in LRs and expressed on splenic marginal zone (MZ) macrophages. The DC-SIGN-C1q or SIGN-R1-C1q complex could mediate the immunoglobulin (Ig)-independent classical complement pathway against Streptococcus pneumoniae. Precise roles of LRs during this complement pathway are unknown. Here we show that LRs are indispensable for accelerating the DC-SIGN- or SIGN-R1-mediated classical complement pathway against S. pneumoniae, thus facilitating rapid clearance of the pathogen. The trimolecular complex of SIGN-R1-C1q-C4 was exclusively enriched in LRs of splenic MZ macrophages and their localization was essential for activating C3 catabolism and enhancing pneumococcal clearance, which were abolished in SIGN-R1-knockout mice. However, DC-SIGN replacement on splenic MZ macrophage’s LRs of SIGN-R1-depleted mice reversed these defects. Disruption of LRs dramatically reduced pneumococcal uptake and decomposition. Additionally, DC- SIGN, C1q, C4, and C3 were obviously distributed in splenic LRs of cadavers. Therefore, LRs on splenic SIGN-R1(+) or DC-SIGN(+) macrophages could provide spatially confined and optimal bidirectional platforms, not only for usual intracellular events, for example recognition and phagocytosis of pathogens, but also an unusual extracellular event such as the complement system. These findings improve our understanding of the orchestrated roles of the spleen, unraveling a new innate immune system initiated from splenic MZ LRs, and yielding answers to several long-standing problems, including the need to understand the profound role of LRs in innate immunity, the need to identify how such a small portion of splenic SIGN-R1(+) macrophages (<0.05% of splenic macrophages) effectively resist S. pneumoniae, and the need to understand how LRs can promote the protective function of DC-SIGN against S. pneumoniae in the human spleen.",2019 Sep 9,"['Yang, Seung Woo', 'Park, Jin-Yeon', 'Choi, Hyeongjwa', 'Yun, Tae Jin', 'Choi, Woo-Sung', 'Kim, Min-Kyung', 'Lee, Yun Kyung', 'Park, Min', 'Jin, Yihwa', 'Joo, Jin Soo', 'Choi, In-Soo', 'Park, Seung Hwa', 'Hwang, Han Sung', 'Kang, Young-Sun']",Cell Death Discov,,,False
13b00804957f2bc0d7c884207e32d67accf06aa5,PMC,Dominant role of splenic marginal zone lipid rafts in the classical complement pathway against S. pneumoniae,http://dx.doi.org/10.1038/s41420-019-0213-3,PMC6733876,31531231,CC BY,"Lipid rafts (LRs) play crucial roles in complex physiological processes, modulating innate and acquired immune responses to pathogens. The transmembrane C-type lectins human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and its mouse homolog SIGN-R1 are distributed in LRs and expressed on splenic marginal zone (MZ) macrophages. The DC-SIGN-C1q or SIGN-R1-C1q complex could mediate the immunoglobulin (Ig)-independent classical complement pathway against Streptococcus pneumoniae. Precise roles of LRs during this complement pathway are unknown. Here we show that LRs are indispensable for accelerating the DC-SIGN- or SIGN-R1-mediated classical complement pathway against S. pneumoniae, thus facilitating rapid clearance of the pathogen. The trimolecular complex of SIGN-R1-C1q-C4 was exclusively enriched in LRs of splenic MZ macrophages and their localization was essential for activating C3 catabolism and enhancing pneumococcal clearance, which were abolished in SIGN-R1-knockout mice. However, DC-SIGN replacement on splenic MZ macrophage’s LRs of SIGN-R1-depleted mice reversed these defects. Disruption of LRs dramatically reduced pneumococcal uptake and decomposition. Additionally, DC- SIGN, C1q, C4, and C3 were obviously distributed in splenic LRs of cadavers. Therefore, LRs on splenic SIGN-R1(+) or DC-SIGN(+) macrophages could provide spatially confined and optimal bidirectional platforms, not only for usual intracellular events, for example recognition and phagocytosis of pathogens, but also an unusual extracellular event such as the complement system. These findings improve our understanding of the orchestrated roles of the spleen, unraveling a new innate immune system initiated from splenic MZ LRs, and yielding answers to several long-standing problems, including the need to understand the profound role of LRs in innate immunity, the need to identify how such a small portion of splenic SIGN-R1(+) macrophages (<0.05% of splenic macrophages) effectively resist S. pneumoniae, and the need to understand how LRs can promote the protective function of DC-SIGN against S. pneumoniae in the human spleen.",2019 Sep 9,"['Yang, Seung Woo', 'Park, Jin-Yeon', 'Choi, Hyeongjwa', 'Yun, Tae Jin', 'Choi, Woo-Sung', 'Kim, Min-Kyung', 'Lee, Yun Kyung', 'Park, Min', 'Jin, Yihwa', 'Joo, Jin Soo', 'Choi, In-Soo', 'Park, Seung Hwa', 'Hwang, Han Sung', 'Kang, Young-Sun']",Cell Death Discov,,,False
a5b61a0c00daea67b98e23a9210b108dab2070c3,PMC,Dominant role of splenic marginal zone lipid rafts in the classical complement pathway against S. pneumoniae,http://dx.doi.org/10.1038/s41420-019-0213-3,PMC6733876,31531231,CC BY,"Lipid rafts (LRs) play crucial roles in complex physiological processes, modulating innate and acquired immune responses to pathogens. The transmembrane C-type lectins human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and its mouse homolog SIGN-R1 are distributed in LRs and expressed on splenic marginal zone (MZ) macrophages. The DC-SIGN-C1q or SIGN-R1-C1q complex could mediate the immunoglobulin (Ig)-independent classical complement pathway against Streptococcus pneumoniae. Precise roles of LRs during this complement pathway are unknown. Here we show that LRs are indispensable for accelerating the DC-SIGN- or SIGN-R1-mediated classical complement pathway against S. pneumoniae, thus facilitating rapid clearance of the pathogen. The trimolecular complex of SIGN-R1-C1q-C4 was exclusively enriched in LRs of splenic MZ macrophages and their localization was essential for activating C3 catabolism and enhancing pneumococcal clearance, which were abolished in SIGN-R1-knockout mice. However, DC-SIGN replacement on splenic MZ macrophage’s LRs of SIGN-R1-depleted mice reversed these defects. Disruption of LRs dramatically reduced pneumococcal uptake and decomposition. Additionally, DC- SIGN, C1q, C4, and C3 were obviously distributed in splenic LRs of cadavers. Therefore, LRs on splenic SIGN-R1(+) or DC-SIGN(+) macrophages could provide spatially confined and optimal bidirectional platforms, not only for usual intracellular events, for example recognition and phagocytosis of pathogens, but also an unusual extracellular event such as the complement system. These findings improve our understanding of the orchestrated roles of the spleen, unraveling a new innate immune system initiated from splenic MZ LRs, and yielding answers to several long-standing problems, including the need to understand the profound role of LRs in innate immunity, the need to identify how such a small portion of splenic SIGN-R1(+) macrophages (<0.05% of splenic macrophages) effectively resist S. pneumoniae, and the need to understand how LRs can promote the protective function of DC-SIGN against S. pneumoniae in the human spleen.",2019 Sep 9,"['Yang, Seung Woo', 'Park, Jin-Yeon', 'Choi, Hyeongjwa', 'Yun, Tae Jin', 'Choi, Woo-Sung', 'Kim, Min-Kyung', 'Lee, Yun Kyung', 'Park, Min', 'Jin, Yihwa', 'Joo, Jin Soo', 'Choi, In-Soo', 'Park, Seung Hwa', 'Hwang, Han Sung', 'Kang, Young-Sun']",Cell Death Discov,,,False
65ba5bec72bd79d015ebe129eae707da149fef94,PMC,Dominant role of splenic marginal zone lipid rafts in the classical complement pathway against S. pneumoniae,http://dx.doi.org/10.1038/s41420-019-0213-3,PMC6733876,31531231,CC BY,"Lipid rafts (LRs) play crucial roles in complex physiological processes, modulating innate and acquired immune responses to pathogens. The transmembrane C-type lectins human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and its mouse homolog SIGN-R1 are distributed in LRs and expressed on splenic marginal zone (MZ) macrophages. The DC-SIGN-C1q or SIGN-R1-C1q complex could mediate the immunoglobulin (Ig)-independent classical complement pathway against Streptococcus pneumoniae. Precise roles of LRs during this complement pathway are unknown. Here we show that LRs are indispensable for accelerating the DC-SIGN- or SIGN-R1-mediated classical complement pathway against S. pneumoniae, thus facilitating rapid clearance of the pathogen. The trimolecular complex of SIGN-R1-C1q-C4 was exclusively enriched in LRs of splenic MZ macrophages and their localization was essential for activating C3 catabolism and enhancing pneumococcal clearance, which were abolished in SIGN-R1-knockout mice. However, DC-SIGN replacement on splenic MZ macrophage’s LRs of SIGN-R1-depleted mice reversed these defects. Disruption of LRs dramatically reduced pneumococcal uptake and decomposition. Additionally, DC- SIGN, C1q, C4, and C3 were obviously distributed in splenic LRs of cadavers. Therefore, LRs on splenic SIGN-R1(+) or DC-SIGN(+) macrophages could provide spatially confined and optimal bidirectional platforms, not only for usual intracellular events, for example recognition and phagocytosis of pathogens, but also an unusual extracellular event such as the complement system. These findings improve our understanding of the orchestrated roles of the spleen, unraveling a new innate immune system initiated from splenic MZ LRs, and yielding answers to several long-standing problems, including the need to understand the profound role of LRs in innate immunity, the need to identify how such a small portion of splenic SIGN-R1(+) macrophages (<0.05% of splenic macrophages) effectively resist S. pneumoniae, and the need to understand how LRs can promote the protective function of DC-SIGN against S. pneumoniae in the human spleen.",2019 Sep 9,"['Yang, Seung Woo', 'Park, Jin-Yeon', 'Choi, Hyeongjwa', 'Yun, Tae Jin', 'Choi, Woo-Sung', 'Kim, Min-Kyung', 'Lee, Yun Kyung', 'Park, Min', 'Jin, Yihwa', 'Joo, Jin Soo', 'Choi, In-Soo', 'Park, Seung Hwa', 'Hwang, Han Sung', 'Kang, Young-Sun']",Cell Death Discov,,,False
073d6557ccb048fe248c2d4c09a21c33f8632371,PMC,Dominant role of splenic marginal zone lipid rafts in the classical complement pathway against S. pneumoniae,http://dx.doi.org/10.1038/s41420-019-0213-3,PMC6733876,31531231,CC BY,"Lipid rafts (LRs) play crucial roles in complex physiological processes, modulating innate and acquired immune responses to pathogens. The transmembrane C-type lectins human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and its mouse homolog SIGN-R1 are distributed in LRs and expressed on splenic marginal zone (MZ) macrophages. The DC-SIGN-C1q or SIGN-R1-C1q complex could mediate the immunoglobulin (Ig)-independent classical complement pathway against Streptococcus pneumoniae. Precise roles of LRs during this complement pathway are unknown. Here we show that LRs are indispensable for accelerating the DC-SIGN- or SIGN-R1-mediated classical complement pathway against S. pneumoniae, thus facilitating rapid clearance of the pathogen. The trimolecular complex of SIGN-R1-C1q-C4 was exclusively enriched in LRs of splenic MZ macrophages and their localization was essential for activating C3 catabolism and enhancing pneumococcal clearance, which were abolished in SIGN-R1-knockout mice. However, DC-SIGN replacement on splenic MZ macrophage’s LRs of SIGN-R1-depleted mice reversed these defects. Disruption of LRs dramatically reduced pneumococcal uptake and decomposition. Additionally, DC- SIGN, C1q, C4, and C3 were obviously distributed in splenic LRs of cadavers. Therefore, LRs on splenic SIGN-R1(+) or DC-SIGN(+) macrophages could provide spatially confined and optimal bidirectional platforms, not only for usual intracellular events, for example recognition and phagocytosis of pathogens, but also an unusual extracellular event such as the complement system. These findings improve our understanding of the orchestrated roles of the spleen, unraveling a new innate immune system initiated from splenic MZ LRs, and yielding answers to several long-standing problems, including the need to understand the profound role of LRs in innate immunity, the need to identify how such a small portion of splenic SIGN-R1(+) macrophages (<0.05% of splenic macrophages) effectively resist S. pneumoniae, and the need to understand how LRs can promote the protective function of DC-SIGN against S. pneumoniae in the human spleen.",2019 Sep 9,"['Yang, Seung Woo', 'Park, Jin-Yeon', 'Choi, Hyeongjwa', 'Yun, Tae Jin', 'Choi, Woo-Sung', 'Kim, Min-Kyung', 'Lee, Yun Kyung', 'Park, Min', 'Jin, Yihwa', 'Joo, Jin Soo', 'Choi, In-Soo', 'Park, Seung Hwa', 'Hwang, Han Sung', 'Kang, Young-Sun']",Cell Death Discov,,,True
84b4e11342098e8595165eff814c004ec50d3e0e,PMC,The Molecular Aspect of Antitumor Effects of Protease Inhibitor Nafamostat Mesylate and Its Role in Potential Clinical Applications,http://dx.doi.org/10.3389/fonc.2019.00852,PMC6733886,31552177,CC BY,"Nafamostat mesylate (NM), a synthetic serine protease inhibitor first placed on the market by Japan Tobacco in 1986, has been approved to treat inflammatory-related diseases, such as pancreatitis. Recently, an increasing number of studies have highlighted the promising effects of NM in inhibiting cancer progression. Alone or in combination treatments, studies have shown that NM attenuates various malignant tumors, including pancreatic, colorectal, gastric, gallbladder, and hepatocellular cancers. In this review, based on several activating pathways, including the canonical Nuclear factor-κB (NF-κB) signaling pathway, tumor necrosis factor receptor-1 (TNFR1) signaling pathway, and tumorigenesis-related tryptase secreted by mast cells, we summarize the anticancer properties of NM in existing studies both in vitro and in vivo. In addition, the efficacy and side effects of NM in cancer patients are summarized in detail. To further clarify NM's antitumor activities, clinical trials devoted to validating the clinical applications and underlying mechanisms are needed in the future.",2019 Sep 3,"['Chen, Xi', 'Xu, Zhijie', 'Zeng, Shuangshuang', 'Wang, Xiang', 'Liu, Wanli', 'Qian, Long', 'Wei, Jie', 'Yang, Xue', 'Shen, Qiuying', 'Gong, Zhicheng', 'Yan, Yuanliang']",Front Oncol,,,True
20a5ebd5341de218798e2defbca3e14ba15895cb,PMC,Awareness and compliance of dental students and interns toward infection control at Riyadh Elm University,http://dx.doi.org/10.3205/dgkh000326,PMC6734498,31538043,CC BY,"Aim: Dental students have increasing patient contact during their education and clinical years, putting them at high risk of cross-infection; therefore, the purpose of this study was to determine the level of infection control practices among dental students and interns at Riyadh Elm University, Riyadh, Saudi Arabia. Methods: Total of 400 questionnaires were distributed among interns and clinical students at Riyadh Elm University. The questionnaire comprised 32 items assessing infection control practices, and the data were tabulated and analyzed by SPSS to produce descriptive statistics. Results: Three hundred nine questionnaires were answered (response rate 77%).The implementation of different infection control measures was good to excellent, except for hepatitis B vaccination and wearing eye protection: only 76% of males and 83% of females were vaccinated against HBV, and only 30% of males and 26% of females always wore protective glasses. Conclusion: Compared to previous studies, an increased awareness regarding infection control practices among dental students and interns was noticeable. However, greater emphasis on the importance of infection control, especially compliance with HBV vaccination and wearing protective eyewear, is necessary.",2019 Aug 5,"['Binalrimal, Sultan', 'AlDrees, Abdulmajed', 'AlWehaibi, Mohammed', 'AlAsmary, Mohammed', 'AlShammery, Abdulaziz', 'AlHaidri, Essam', 'AlQabbaa, Lama']",GMS Hyg Infect Control,,,True
09417d5a567e93e35a80a241b9459f2b84ef0b0d,PMC,Co-delivery of glycyrrhizin and doxorubicin by alginate nanogel particles attenuates the activation of macrophage and enhances the therapeutic efficacy for hepatocellular carcinoma,http://dx.doi.org/10.7150/thno.35972,PMC6735516,31534548,CC BY,"Nanocarrier drug delivery systems (NDDS) have been paid more attention over conventional drug delivery system for cancer therapy. However, the efficacy is hampered by the fast clearance of activated macrophage from the blood circulation system. In this study, glycyrrhizin (GL) was introduced into alginate (ALG) nanogel particles (NGPs) to construct multifunctional delivery vehicle to decrease the fast clearance of activated macrophage and enhance the anticancer efficacy with the combination therapy of GL and doxorubicin (DOX). Methods: We firstly synthesized the GL-ALG NGPs with intermolecular hydrogen bond and ionic bond as the multifunctional delivery vehicle. The immune response and phagocytosis of macrophage on GL-ALG NGPs were investigated on RAW 264.7 macrophages. The pharmacokinetic study of DOX loaded in GL-ALG NGPs was performed in rats. The active targeting effects of GL-ALG NGPs were further studied on hepatocellular carcinoma cell (HepG2) and H22 tumor-bearing mice. Moreover, the anticancer molecular mechanism of DOX/GL-ALG NGPs was investigated on HepG2 cells in vitro and tumor-bearing mice in vivo. Results: GL-ALG NGPs could not only avoid triggering the immuno-inflammatory responses of macrophages but also decreasing the phagocytosis of macrophage. The bioavailability of DOX was increased about 13.2 times by DOX/GL-ALG NGPs than free DOX in blood. The mice with normal immune functions used in constructing the tumor-bearing mice instead of the nude mouse also indicated the good biocompatibility of NGPs. GL-mediated ALG NGPs exhibited excellent hepatocellular carcinoma targeting effect in vitro and in vivo. The results suggested that the anticancer molecular mechanism of the combination therapy of glycyrrhizin and doxorubicin in ALG NGPs was performed via regulating apoptosis pathway of Bax/Bcl-2 ratio and caspase-3 activity, which was also verified in H22 tumor-bearing mice. Conclusion: DOX/GL-ALG NGPs could attenuate the activation of macrophage and enhance the therapeutic efficacy for hepatocellular carcinoma. Our results suggest that the combination therapy would provide a new strategy for liver cancer treatment.",2019 Aug 14,"['Wang, Qiang-Song', 'Gao, Li-Na', 'Zhu, Xiao-Ning', 'Zhang, Yan', 'Zhang, Chuang-Nian', 'Xu, Dong', 'Cui, Yuan-Lu']",Theranostics,,,True
60e006f4e2f2cb257576139c19d44c3a9404bdf5,PMC,Co-delivery of glycyrrhizin and doxorubicin by alginate nanogel particles attenuates the activation of macrophage and enhances the therapeutic efficacy for hepatocellular carcinoma,http://dx.doi.org/10.7150/thno.35972,PMC6735516,31534548,CC BY,"Nanocarrier drug delivery systems (NDDS) have been paid more attention over conventional drug delivery system for cancer therapy. However, the efficacy is hampered by the fast clearance of activated macrophage from the blood circulation system. In this study, glycyrrhizin (GL) was introduced into alginate (ALG) nanogel particles (NGPs) to construct multifunctional delivery vehicle to decrease the fast clearance of activated macrophage and enhance the anticancer efficacy with the combination therapy of GL and doxorubicin (DOX). Methods: We firstly synthesized the GL-ALG NGPs with intermolecular hydrogen bond and ionic bond as the multifunctional delivery vehicle. The immune response and phagocytosis of macrophage on GL-ALG NGPs were investigated on RAW 264.7 macrophages. The pharmacokinetic study of DOX loaded in GL-ALG NGPs was performed in rats. The active targeting effects of GL-ALG NGPs were further studied on hepatocellular carcinoma cell (HepG2) and H22 tumor-bearing mice. Moreover, the anticancer molecular mechanism of DOX/GL-ALG NGPs was investigated on HepG2 cells in vitro and tumor-bearing mice in vivo. Results: GL-ALG NGPs could not only avoid triggering the immuno-inflammatory responses of macrophages but also decreasing the phagocytosis of macrophage. The bioavailability of DOX was increased about 13.2 times by DOX/GL-ALG NGPs than free DOX in blood. The mice with normal immune functions used in constructing the tumor-bearing mice instead of the nude mouse also indicated the good biocompatibility of NGPs. GL-mediated ALG NGPs exhibited excellent hepatocellular carcinoma targeting effect in vitro and in vivo. The results suggested that the anticancer molecular mechanism of the combination therapy of glycyrrhizin and doxorubicin in ALG NGPs was performed via regulating apoptosis pathway of Bax/Bcl-2 ratio and caspase-3 activity, which was also verified in H22 tumor-bearing mice. Conclusion: DOX/GL-ALG NGPs could attenuate the activation of macrophage and enhance the therapeutic efficacy for hepatocellular carcinoma. Our results suggest that the combination therapy would provide a new strategy for liver cancer treatment.",2019 Aug 14,"['Wang, Qiang-Song', 'Gao, Li-Na', 'Zhu, Xiao-Ning', 'Zhang, Yan', 'Zhang, Chuang-Nian', 'Xu, Dong', 'Cui, Yuan-Lu']",Theranostics,,,False
9f8d663bc0388e20995d91618f776fa6a61a5258,PMC,Risk of Introduction of Infectious Animal Diseases for Europe Based on the Health Situation of North Africa and the Arabian Peninsula,http://dx.doi.org/10.3389/fvets.2019.00293,PMC6737002,31555676,CC BY,"The current growth of the human population, the intensification of animal production, climate change or globalization favors an increase in the transmission of infectious diseases. Risk analysis is the tool that allows the identification of the factors involved in the introduction and the spread of infectious diseases. The main objective of this work is to evaluate the risk of entry of animal infectious zoonotic and non-zoonotic diseases from North Africa and the Arabian Peninsula to countries of the European Union. A probabilistic formulation has been developed to obtain the probabilities of introduction of diseases associated with each possible route of entry in the European Union. The results show that, among the infectious diseases analyzed in this study, avian influenza and Newcastle disease are the ones with a higher risk of entry in the European Union and the wild bird's migration is the route with greater impact. It is confirmed a moderate probability of entry of some vector-borne diseases, bluetongue and epizootic haemorrhagic disease, through wind flow from Morocco, Algeria and Tunisia. Due to the absence of live dromedary movement to Europe, the more likely way of entry of the Middle East respiratory syndrome is through the infected people movement from Saudi Arabia, Kuwait, Qatar and Oman. This study includes different methodologies. A model of vectors dispersion in wind currents has been established to assess the risk of introduction of vector borne diseases. It is applicable both in animal health and public health. A periodical update would be useful to obtain a periodically updated risk analysis and to allow early detection of potential hazard with an increased risk over the previous years.",2019 Sep 4,"['Massó Sagüés, Elena', 'Fernández-Carrión, Eduardo', 'Sánchez-Vizcaíno, Jose Manuel']",Front Vet Sci,,,True
6e2c37e888f6266374356b4dded392359a4695db,PMC,Antiviral Properties of R. tanguticum Nanoparticles on Herpes Simplex Virus Type I In Vitro and In Vivo,http://dx.doi.org/10.3389/fphar.2019.00959,PMC6737004,31555137,CC BY,"Herpes simplex virus type 1 (HSV-1), an enveloped DNA virus, plays a key role in varieties of diseases including recurrent cold sores, keratoconjunctivitis, genital herpes and encephalitis in humans. Great efforts have been made in developing more effective and less side-effects anti-herpes simplex virus agents, including traditional Chinese herbal medicines. In the present study, we evaluated the antiviral efficacy of Rheum tanguticum nanoparticles against HSV-1 in vitro and in vivo. R. tanguticum nanoparticles could inactivate the HSV-1 virions and block the viral attachment and entry into cells. Time-of-addition assay indicated that R. tanguticum nanoparticles could interfere with the entire phase of viral replication. Besides, R. tanguticum nanoparticles showed the ability to inhibit the mRNA expression of HSV-1 immediate early gene ICP4 and early gene ICP8 as well as the expression of viral protein ICP4 and ICP8. Moreover, R. tanguticum nanoparticles have been proved to protect mice against HSV-1 induced lethality by decreasing the viral load and alleviated pathological changes in brain tissues. In conclusion, we demonstrated that R. tanguticum nanoparticles could inhibit HSV-1 infection through multiple mechanisms. These results suggest that R. tanguticum nanoparticles may have novel roles in the treatment of HSV-1 infection.",2019 Sep 4,"['Shen, Meng-xin', 'Ma, Nian', 'Li, Min-ke', 'Liu, Yuan-yuan', 'Chen, Tian', 'Wei, Fei', 'Liu, Dong-ying', 'Hou, Wei', 'Xiong, Hai-rong', 'Yang, Zhan-qiu']",Front Pharmacol,,,True
6aa7d56acd001adebe441f2ec6fa8c96f3d131d4,PMC,Immunomodulation Induced by Host Pathogen Interaction,http://dx.doi.org/10.1155/2019/9710910,PMC6737272,31565663,CC BY,,2019 Aug 29,"['Yassine, Hadi M.', 'Moin, Syed M.', 'Cyprian, Farhan S.', 'Wheatley, Adam K.', 'Nasrallah, Gheyath K.']",J Immunol Res,,,False
868b9ab09cae7afe1d1e2ad2f547adecd4d18ac6,PMC,Surfactant Proteins A and D: Trimerized Innate Immunity Proteins with an Affinity for Viral Fusion Proteins,http://dx.doi.org/10.1159/000492974,PMC6738215,30293076,CC BY,"Innate recognition of viruses is an essential part of the immune response to viral pathogens. This is integral to the maintenance of healthy lungs, which are free from infection and efficient at gaseous exchange. An important component of innate immunity for identifying viruses is the family of C-type collagen-containing lectins, also known as collectins. These secreted, soluble proteins are pattern recognition receptors (PRRs) which recognise pathogen-associated molecular patterns (PAMPs), including viral glycoproteins. These innate immune proteins are composed of trimerized units which oligomerise into higher-order structures and facilitate the clearance of viral pathogens through multiple mechanisms. Similarly, many viral surface proteins form trimeric configurations, despite not showing primary protein sequence similarities across the virus classes and families to which they belong. In this review, we discuss the role of the lung collectins, i.e., surfactant proteins A and D (SP-A and SP-D) in viral recognition. We focus particularly on the structural similarity and complementarity of these trimeric collectins with the trimeric viral fusion proteins with which, we hypothesise, they have elegantly co-evolved. Recombinant versions of these innate immune proteins may have therapeutic potential in a range of infectious and inflammatory lung diseases including anti-viral therapeutics.",2018 Dec 5,"['Watson, Alastair', 'Phipps, Maximillian J.S.', 'Clark, Howard W.', 'Skylaris, Chris-Kriton', 'Madsen, Jens']",J Innate Immun,,,True
778eb107d6ddffb02ad911aa14802f662db00b30,PMC,Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation,http://dx.doi.org/10.7554/eLife.46681,PMC6739877,31403400,CC BY,"Knowledge of the host factors required for norovirus replication has been hindered by the challenges associated with culturing human noroviruses. We have combined proteomic analysis of the viral translation and replication complexes with a CRISPR screen, to identify host factors required for norovirus infection. The core stress granule component G3BP1 was identified as a host factor essential for efficient human and murine norovirus infection, demonstrating a conserved function across the Norovirus genus. Furthermore, we show that G3BP1 functions in the novel paradigm of viral VPg-dependent translation initiation, contributing to the assembly of translation complexes on the VPg-linked viral positive sense RNA genome by facilitating ribosome recruitment. Our data uncovers a novel function for G3BP1 in the life cycle of positive sense RNA viruses and identifies the first host factor with pan-norovirus pro-viral activity.",,"['Hosmillo, Myra', 'Lu, Jia', 'McAllaster, Michael R', 'Eaglesham, James B', 'Wang, Xinjie', 'Emmott, Edward', 'Domingues, Patricia', 'Chaudhry, Yasmin', 'Fitzmaurice, Tim J', 'Tung, Matthew KH', 'Panas, Marc Dominik', 'McInerney, Gerald', 'Locker, Nicolas', 'Wilen, Craig B', 'Goodfellow, Ian G']",eLife.; 8:e46681,,,True
5688f38645b50f19f5b36727b64e89bf73ad453c,PMC,Combination Antifungal Therapy for Invasive Mold Infections Among Pediatric Patients with Hematological Malignancies: Data from A Real-Life Case-Series,http://dx.doi.org/10.20411/pai.v4i2.299,PMC6742350,31538132,CC BY,"BACKGROUND: Invasive mold infections in children with hematological malignancies are associated with high mortality rates. The use of combination antifungal therapy in cases with a severe clinical course is increasing, although information on the efficacy and safety of this approach is limited. METHODS: We present a case series of 13 children affected by hemato-oncological disorders who received combination antifungal therapy for invasive mold infections at our center (Pediatric Hematology, San Gerardo Hospital, Monza, Italy) from 2011 to 2016, with the aim of describing their clinical characteristics, types of infections, treatment regimens, clinical outcomes, and treatment safety. Medical records were retrospectively reviewed in order to describe patients' characteristics. RESULTS: Combination antifungal therapy included liposomal amphotericin associated with caspofungin (5/13, 38.4%), voriconazole (5/13, 38.4%), or posaconazole (3/13, 23.1%). The 12-week treatment response rate was 69.2% (6/13 patients showed complete response, 3/13 partial response). The crude mortality was 30.7% (4/13): half was related to invasive mold infections (2/13, 15.38%) and half to disease progression (2/13, 15.38%). Overall, treatment was well tolerated, and we did not observe any permanent discontinuation of antifungals due to related side effects. CONCLUSIONS: In our experience, combination antifungal therapy seems to be a safe option in immunocompromised children with invasive mold infections. Well-designed studies are needed to confirm the safety of this approach and to better understand its efficacy in the pediatric setting.",2019 Sep 5,"['Peri, Anna Maria', 'Verna, Marta', 'Biffi, Stefano', 'Alagna, Laura', 'Longhi, Benedetta', 'Migliorino, Guglielmo Marco', 'Foresti, Sergio', 'Bandera, Alessandra', 'Rovelli, Attilio', 'Rizzari, Carmelo', 'Gori, Andrea', 'Colombini, Antonella']",Pathog Immun,,,True
7771f0ca13a747e3c8030edb90986b6853b2780b,PMC,Aminopeptidase N-null neonatal piglets are protected from transmissible gastroenteritis virus but not porcine epidemic diarrhea virus,http://dx.doi.org/10.1038/s41598-019-49838-y,PMC6742759,31515498,CC BY,"Swine enteric diseases have caused significant economic loss and have been considered as the major threat to the global swine industry. Several coronaviruses, including transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV), have been identified as the causative agents of these diseases. Effective measures to control these diseases are lacking. The major host cells of transmissible gastroenteritis virus and porcine epidemic diarrhea virus have thought to be epithelial cells on small intestine villi. Aminopeptidase-N (APN) has been described as the putative receptor for entry of transmissible gastroenteritis virus and porcine epidemic diarrhea virus into cells in vitro. Recently, Whitworth et al. have reported that APN knockout pigs are resistant to TGEV but not PEDV after weaning. However, it remains unclear if APN-null neonatal pigs are protected from TGEV. Here we report the generation of APN-null pigs by using CRISPR/Cas9 technology followed by somatic cell nuclear transfer. APN-null pigs are produced with normal pregnancy rate and viability, indicating lack of APN is not embryonic lethal. After viral challenge, APN-null neonatal piglets are resistant to highly virulent transmissible gastroenteritis virus. Histopathological analyses indicate APN-null pigs exhibit normal small intestine villi, while wildtype pigs show typical lesions in small intestines. Immunochemistry analyses confirm that no transmissible gastroenteritis virus antigen is detected in target tissues in APN-null piglets. However, upon porcine epidemic diarrhea virus challenge, APN-null pigs are still susceptible with 100% mortality. Collectively, this report provides a viable tool for producing animals with enhanced resistance to TGEV and clarifies that APN is dispensable for the PEDV infection in pigs.",2019 Sep 12,"['Luo, Lei', 'Wang, Shaohua', 'Zhu, Lin', 'Fan, Baochao', 'Liu, Tong', 'Wang, Lefeng', 'Zhao, Panpan', 'Dang, Yanna', 'Sun, Pei', 'Chen, Jianwen', 'Zhang, Yunhai', 'Chang, Xinjian', 'Yu, Zhengyu', 'Wang, Huanan', 'Guo, Rongli', 'Li, Bin', 'Zhang, Kun']",Sci Rep,,,False
3e168aef44683549563640db5ca32da62be4e27b,PMC,Aminopeptidase N-null neonatal piglets are protected from transmissible gastroenteritis virus but not porcine epidemic diarrhea virus,http://dx.doi.org/10.1038/s41598-019-49838-y,PMC6742759,31515498,CC BY,"Swine enteric diseases have caused significant economic loss and have been considered as the major threat to the global swine industry. Several coronaviruses, including transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV), have been identified as the causative agents of these diseases. Effective measures to control these diseases are lacking. The major host cells of transmissible gastroenteritis virus and porcine epidemic diarrhea virus have thought to be epithelial cells on small intestine villi. Aminopeptidase-N (APN) has been described as the putative receptor for entry of transmissible gastroenteritis virus and porcine epidemic diarrhea virus into cells in vitro. Recently, Whitworth et al. have reported that APN knockout pigs are resistant to TGEV but not PEDV after weaning. However, it remains unclear if APN-null neonatal pigs are protected from TGEV. Here we report the generation of APN-null pigs by using CRISPR/Cas9 technology followed by somatic cell nuclear transfer. APN-null pigs are produced with normal pregnancy rate and viability, indicating lack of APN is not embryonic lethal. After viral challenge, APN-null neonatal piglets are resistant to highly virulent transmissible gastroenteritis virus. Histopathological analyses indicate APN-null pigs exhibit normal small intestine villi, while wildtype pigs show typical lesions in small intestines. Immunochemistry analyses confirm that no transmissible gastroenteritis virus antigen is detected in target tissues in APN-null piglets. However, upon porcine epidemic diarrhea virus challenge, APN-null pigs are still susceptible with 100% mortality. Collectively, this report provides a viable tool for producing animals with enhanced resistance to TGEV and clarifies that APN is dispensable for the PEDV infection in pigs.",2019 Sep 12,"['Luo, Lei', 'Wang, Shaohua', 'Zhu, Lin', 'Fan, Baochao', 'Liu, Tong', 'Wang, Lefeng', 'Zhao, Panpan', 'Dang, Yanna', 'Sun, Pei', 'Chen, Jianwen', 'Zhang, Yunhai', 'Chang, Xinjian', 'Yu, Zhengyu', 'Wang, Huanan', 'Guo, Rongli', 'Li, Bin', 'Zhang, Kun']",Sci Rep,,,True
02998402c64a65e3ea2fd0fdd8f688aeebda6192,PMC,Complete Genome Sequencing of a Novel Strain of Sapelovirus A Circulating in Vietnam,http://dx.doi.org/10.1128/MRA.00959-19,PMC6742800,31515349,CC BY,Sapelovirus A (SV-A) is currently spreading as an enteric pathogen of pigs worldwide. We isolated SV-A strain XTND/2018 from the small intestine of a dead pig with severe diarrhea in the north of Vietnam and determined the genomic sequence. This is the first report of the genomic sequence of SV-A circulating in Vietnam.,2019 Sep 12,"['Dang, Hoang Vu', 'Kato, Tomoko', 'Nishi, Tatsuya', 'Tran, Ha Thanh', 'Miyazawa, Kohtaro', 'Kokuho, Takehiro']",Microbiol Resour Announc,,,True
26d8317a46bcbe3ec8ff5aa98de2a848fbd358ca,PMC,Molecular detection of respiratory pathogens and typing of human rhinovirus of adults hospitalized for exacerbation of asthma and chronic obstructive pulmonary disease,http://dx.doi.org/10.1186/s12931-019-1181-0,PMC6743175,31519188,CC BY,"BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and asthma are associated with a variety of precipitating factors including infection. This study assessed the infective viral etiologies by real-time multiplex polymerase chain reaction of patients hospitalized with AECOPD and asthma exacerbations. In addition, infective etiologies were assessed for association with the clinical outcome of the patients. METHODS: Adults admitted with AECOPD and asthma exacerbations between August 2016 and July 2017 were recruited. Nasopharyngeal aspirate (NPA) samples were obtained from the patients within 1–2 days of admission and subjected to pathogen detection and human rhinovirus (HRV) typing. RESULTS: Altogether 402 patients with AECOPD, 80 stable COPD, 100 asthma exacerbation and 21 stable asthma subjects were recruited. Among those admitted for AECOPD and asthma exacerbations, 141(35.1%) and 45(45.0%) respectively had pathogens identified in the NPA specimens. The commonest virus identified was influenza A followed by HRV. HRV typing identified HRV-A and HRV-C as the more common HRV with a wide variety of genotypes. Identification of pathogens in NPA or HRV typing otherwise did not affect clinical outcomes including the hospital length of stay, readmission rates and mortality except that identification of pathogens in asthma exacerbation was associated with a lower rate of readmissions at 30 and 60 days. CONCLUSIONS: Many respiratory viruses were associated with AECOPD and asthma exacerbation. HRV-A and HRV-C were the more common HRV associated with exacerbations. Identification of pathogens in NPA was associated with less readmissions for asthma patients at 30 and 60 days. TRIAL REGISTRATION: ClinicalTrials.gov NCT02866357. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at10.1186/s12931-019-1181-0.",2019 Sep 13,"['Ko, Fanny Wai-san', 'Chan, Paul Kay-sheung', 'Chan, Renee W. Y.', 'Chan, Ka-Pang', 'Ip, April', 'Kwok, Angela', 'Ngai, Jenny Chun-li', 'Ng, So-Shan', 'On, Chan Tat', 'Hui, David Shu-cheong']",Respir Res,,,True
5aebac2302d94acc406291d65cc7c538ab71dae1,PMC,Targeting viral entry as a strategy for broad-spectrum antivirals,http://dx.doi.org/10.12688/f1000research.19694.1,PMC6743247,31559009,CC BY,"The process of entry into a host cell is a key step in the life cycle of most viruses. In recent years, there has been a significant increase in our understanding of the routes and mechanisms of entry for a number of these viruses. This has led to the development of novel broad-spectrum antiviral approaches that target host cell proteins and pathways, in addition to strategies focused on individual viruses or virus families. Here we consider a number of these approaches and their broad-spectrum potential.",2019 Sep 12,"['Mazzon, Michela', 'Marsh, Mark']",F1000Res,,,True
4b22861aa553b97e42e6a1b95b744e0ec2dcd6b2,PMC,Healthcare Workers’ Strategies for Doffing Personal Protective Equipment,http://dx.doi.org/10.1093/cid/ciz613,PMC6743502,31517970,CC BY,"BACKGROUND: Personal protective equipment (PPE) helps protect healthcare workers (HCWs) from pathogens and prevents cross-contamination. PPE effectiveness is often undermined by inappropriate doffing methods. Our knowledge of how HCWs approach doffing PPE in practice is limited. In this qualitative study, we examine HCWs’ perspectives about doffing PPE. METHODS: Thirty participants at a Midwestern academic hospital were recruited and assigned to 1 of 3 doffing simulation scenarios: 3 mask designs (n = 10), 2 gown designs (n = 10), or 2 glove designs (n = 10). Participants were instructed to doff PPE as they would in routine practice. Their performances were video-recorded and reviewed with participants. Semistructured interviews about their doffing approaches were conducted and audio-recorded, then transcribed and thematically analyzed. RESULTS: Three overarching themes were identified in interviews: doffing strategies, cognitive processes, and barriers and facilitators. Doffing strategies included doffing safely (minimizing self-contamination) and doffing expediently (eg, ripping PPE off). Cognitive processes during doffing largely pertained to tracking contaminated PPE surfaces, examining PPE design cues (eg, straps), or improvising based on prior experience from training or similar PPE designs. Doffing barriers and facilitators typically related to PPE design, such as PPE fit (or lack of it) and fastener type. Some participants also described personal barriers (eg, glasses, long hair); however, some PPE designs helped mitigate these barriers. CONCLUSIONS: Efforts to improve HCWs’ doffing performance need to address HCWs’ preferences for both safety and expediency when using PPE, which has implications for PPE design, training approaches, and hospital policies and procedures.",2019 Oct 1,"['Baloh, Jure', 'Reisinger, Heather Schacht', 'Dukes, Kimberly', 'da Silva, Jaqueline Pereira', 'Salehi, Hugh P', 'Ward, Melissa', 'Chasco, Emily E', 'Pennathur, Priyadarshini R', 'Herwaldt, Loreen']",Clin Infect Dis,,,True
ae4c5ad260f38772c10120bb77062912dcce189e,PMC,Acute human bocavirus 1 infection in child with life-threatening bilateral bronchiolitis and right-sided pneumonia: a case report,http://dx.doi.org/10.1186/s13256-019-2222-5,PMC6744643,31519214,CC BY,"BACKGROUND: Human bocavirus 1 is a commonly detected human parvovirus. Many studies have shown human bocavirus 1 as a pathogen in association with acute respiratory tract infections in children. However, because human bocavirus 1 persists in the upper airways for extensive time periods after acute infection, the definition and diagnostics of acute human bocavirus 1 infection is challenging. Until now, detection of human bocavirus 1 exclusively, high viral load in respiratory samples, and viremia have been associated with a clinical picture of acute respiratory illness. There are no studies showing detection of human bocavirus 1 messenger ribonucleic acid in the peripheral blood mononuclear cells as a diagnostic marker for acute lower respiratory tract infection. CASE PRESENTATION: We report the case of a 17-month-old Latvian boy who presented in intensive care unit with acute bilateral bronchiolitis, with a history of rhinorrhea and cough for 6 days and fever for the last 2 days prior to admission, followed by severe respiratory distress and tracheal intubation. Human bocavirus 1 was the only respiratory virus detected by a qualitative multiplex polymerase chain reaction panel. For the diagnosis of acute human bocavirus 1 infection, both molecular and serological approaches were used. Human bocavirus 1 deoxyribonucleic acid (DNA) was detected simultaneously in nasopharyngeal aspirate, stool, and blood, as well as in the corresponding cell-free blood plasma by qualitative and quantitative polymerase chain reaction, revealing high DNA-copy numbers in nasopharyngeal aspirate and stool. Despite a low-load viremia, human bocavirus 1 messenger ribonucleic acid was found in the peripheral blood mononuclear cells. For detection of human bocavirus 1-specific antibodies, non-competitive immunoglobulin M and competitive immunoglobulin G enzyme immunoassays were used. The plasma was positive for both human bocavirus 1-specific immunoglobulin M and immunoglobulin G antibodies. CONCLUSIONS: The presence of human bocavirus 1 genomic DNA in blood plasma and human bocavirus 1 messenger ribonucleic acid in peripheral blood mononuclear cells together with human bocavirus 1-specific immunoglobulin M are markers of acute human bocavirus 1 infection that may cause life-threatening acute bronchiolitis.",2019 Sep 14,"['Ziemele, Inga', 'Xu, Man', 'Vilmane, Anda', 'Rasa-Dzelzkaleja, Santa', 'Hedman, Lea', 'Hedman, Klaus', 'Söderlund-Venermo, Maria', 'Nora-Krukle, Zaiga', 'Murovska, Modra', 'Gardovska, Dace']",J Med Case Rep,,,True
d44554968fffa118597a03b93a4a3fa6150d8895,PMC,A novel biotinylated nanobody-based blocking ELISA for the rapid and sensitive clinical detection of porcine epidemic diarrhea virus,http://dx.doi.org/10.1186/s12951-019-0531-x,PMC6745792,31526383,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV), which is characterized by severe watery diarrhea, vomiting, dehydration and a high mortality rate in piglets, leads to enormous economic losses to the pork industry and remains a large challenge worldwide. Thus, a rapid and reliable method is required for epidemiological investigations and to evaluate the effect of immunization. However, the current diagnostic methods for PEDV are time-consuming and very expensive and rarely meet the requirements for clinical application. Nanobodies have been used in the clinic to overcome these problems because of the advantages of their easy expression and high level of stability. In the present work, a novel biotinylated nanobody-based blocking ELISA (bELISA) was developed to detect anti-PEDV antibodies in clinical pig serum. RESULTS: Using phage display technology and periplasmic extraction ELISA (PE-ELISA), anti-PEDV N protein nanobodies from three strains of PEDV were successfully isolated after three consecutive rounds of bio-panning from a high quality phage display VHH library. Then, purified Nb2-Avi-tag fusion protein was biotinylated in vitro. A novel bELISA was subsequently developed for the first time with biotinylated Nb2. The cutoff value for bELISA was 29.27%. One hundred and fifty clinical serum samples were tested by both newly developed bELISA and commercial kits. The sensitivity and specificity of bELISA were 100% and 93.18%, respectively, and the coincidence rate between the two methods was 94%. CONCLUSIONS: In brief, bELISA is a rapid, low-cost, reliable and useful nanobody-based tool for the serological evaluation of current PEDV vaccines efficacy and indirect diagnosis of PEDV infection.",2019 Sep 16,"['Ma, Zhiqian', 'Wang, Tianyu', 'Li, Zhiwei', 'Guo, Xuyang', 'Tian, Yangsheng', 'Li, Yang', 'Xiao, Shuqi']",J Nanobiotechnology,,,True
78138c22f695836b6da58f74c78a8066204a2b12,PMC,Marburg virus regulates the IRE1/XBP1-dependent unfolded protein response to ensure efficient viral replication,http://dx.doi.org/10.1080/22221751.2019.1659552,PMC6746283,31495285,CC BY,"Viruses regulate cellular signalling pathways to ensure optimal viral replication. During Marburg virus (MARV) infection, large quantities of the viral glycoprotein GP are produced in the ER; this may result in the activation of the unfolded protein response (UPR). The most conserved pathway to trigger UPR is initiated by IRE1. Activation of IRE1 results in auto-phosphorylation, splicing of the XBP1 mRNA and translation of the XBP1s protein. XBP1s binds cis-acting UPR elements (UPRE) which leads to the enhanced expression of genes which should restore ER homeostasis. XBP1u protein is translated, if IRE1 is not activated. Here we show that ectopic expression of MARV GP activated the IRE1-XBP1 axis of UPR as monitored by UPRE luciferase assays. However, while at 24 h of infection with MARV IRE1 was phosphorylated, expression of XBP1s was only slightly enhanced and UPRE activity was not detected. The IRE1-XBP1 axis was not active at 48 h p.i. Co-expression studies of MARV proteins demonstrated that the MARV protein VP30 suppressed UPRE activation. Co-immunoprecipitation analyses revealed an RNA-dependent interaction of VP30 with XBP1u. Knock-out of IRE1 supported MARV infection at late time points. Taken together, these results suggest that efficient MARV propagation requires specific regulation of IRE1 activity.",2019 Sep 7,"['Rohde, Cornelius', 'Becker, Stephan', 'Krähling, Verena']",Emerg Microbes Infect,,,True
d99e678f4842732a81e53bc04ba3a186866706e1,PMC,Marburg virus regulates the IRE1/XBP1-dependent unfolded protein response to ensure efficient viral replication,http://dx.doi.org/10.1080/22221751.2019.1659552,PMC6746283,31495285,CC BY,"Viruses regulate cellular signalling pathways to ensure optimal viral replication. During Marburg virus (MARV) infection, large quantities of the viral glycoprotein GP are produced in the ER; this may result in the activation of the unfolded protein response (UPR). The most conserved pathway to trigger UPR is initiated by IRE1. Activation of IRE1 results in auto-phosphorylation, splicing of the XBP1 mRNA and translation of the XBP1s protein. XBP1s binds cis-acting UPR elements (UPRE) which leads to the enhanced expression of genes which should restore ER homeostasis. XBP1u protein is translated, if IRE1 is not activated. Here we show that ectopic expression of MARV GP activated the IRE1-XBP1 axis of UPR as monitored by UPRE luciferase assays. However, while at 24 h of infection with MARV IRE1 was phosphorylated, expression of XBP1s was only slightly enhanced and UPRE activity was not detected. The IRE1-XBP1 axis was not active at 48 h p.i. Co-expression studies of MARV proteins demonstrated that the MARV protein VP30 suppressed UPRE activation. Co-immunoprecipitation analyses revealed an RNA-dependent interaction of VP30 with XBP1u. Knock-out of IRE1 supported MARV infection at late time points. Taken together, these results suggest that efficient MARV propagation requires specific regulation of IRE1 activity.",2019 Sep 7,"['Rohde, Cornelius', 'Becker, Stephan', 'Krähling, Verena']",Emerg Microbes Infect,,,False
380ffac0468974d60549293c37047bd307218587,PMC,Porcine deltacoronavirus causes diarrhea in various ages of field-infected pigs in China,http://dx.doi.org/10.1042/BSR20190676,PMC6746998,31488617,CC BY,"Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes acute diarrhea in suckling piglets. In Henan province of China, three swine farms broke out diarrhea in different ages of pigs during June of 2017, March of 2018 and January of 2019, respectively. PCR method, Taqman real-time RT-PCR method, sequencing, histopathology and immunohistochemistry (IHC) were conducted with the collected samples, and the results showed that PDCoV was detected among the suckling piglets, commercial fattening pigs and sows with diarrhea. PDCoV-infected suckling piglets were characterized with thin and transparent intestinal walls from colon to caecum, spot hemorrhage at mesentery and intestinal bleeding. PDCoV RNA was detected in multiple organs and tissues by Taqman real-time RT-PCR, which had high copies in ileum, inguinal lymph node, rectum and spleen. PDCoV antigen was detected in the basal layer of jejunum and ileum by IHC. In this research, we found that PDCoV could infect various ages of farmed pigs with watery diarrhea and anorexia in different seasons in a year.",2019 Sep 16,"['Li, Bingxiao', 'Zheng, Lanlan', 'Li, Haiyan', 'Ding, Qingwen', 'Wang, Yabin', 'Wei, Zhanyong']",Biosci Rep,,,True
05252b1035b0647c566b72ef0ef269f3fc385c90,PMC,#CDCGrandRounds and #VitalSigns: A Twitter Analysis,http://dx.doi.org/10.29024/aogh.2381,PMC6748269,30779521,CC BY,"BACKGROUND: The CDC hosts monthly panel presentations titled ‘Public Health Grand Rounds’ and publishes monthly reports known as Vital Signs. Hashtags #CDCGrandRounds and #VitalSigns were used to promote them on Twitter. OBJECTIVES: This study quantified the effect of hashtag count, mention count, and URL count and attaching visual cues to #CDCGrandRounds or #VitalSigns tweets on their retweet frequency. METHODS: Through Twitter Search Application Programming Interface, original tweets containing the hashtag #CDCGrandRounds (n = 6,966; April 21, 2011–October 25, 2016) and the hashtag #VitalSigns (n = 15,015; March 19, 2013–October 31, 2016) were retrieved respectively. Negative binomial regression models were applied to each corpus to estimate the associations between retweet frequency and three predictors (hashtag count, mention count, and URL link count). Each corpus was sub-set into cycles (#CDCGrandRounds: n = 58, #VitalSigns: n = 42). We manually coded the 30 tweets with the highest number of retweets for each cycle, whether it contained visual cues (images or videos). Univariable negative binomial regression models were applied to compute the prevalence ratio (PR) of retweet frequency for each cycle, between tweets with and without visual cues. FINDINGS: URL links increased retweet frequency in both corpora; effects of hashtag count and mention count differed between the two corpora. Of the 58 #CDCGrandRounds cycles, 29 were found to have statistically significantly different retweet frequencies between tweets with and without visual cues. Of these 29 cycles, one had a PR estimate < 1; twenty-four, PR > 1 but < 3; and four, PR > 3. Of the 42 #VitalSigns cycles, 19 were statistically significant. Of these 19 cycles, six were PR > 1 and < 3; and thirteen, PR > 3. CONCLUSIONS: The increase of retweet frequency through attaching visual cues varied across cycles for original tweets with #CDCGrandRounds and #VitalSigns. Future research is needed to determine the optimal choice of visual cues to maximize the influence of public health tweets.",,"['Jackson, Ashley M.', 'Mullican, Lindsay A.', 'Yin, Jingjing', 'Ho Tse, Zion Tsz', 'Liang, Hai', 'Fu, King-Wa', 'Ahweyevu, Jennifer O.', 'Jenkins, Jimmy J.', 'Saroha, Nitin', 'Fung, Isaac Chun-Hai']",Ann Glob Health.; 84(4):710-716,,,True
fb4ca5437ec6856a1f57ece571120c64f17b13ad,PMC,#CDCGrandRounds and #VitalSigns: A Twitter Analysis,http://dx.doi.org/10.29024/aogh.2381,PMC6748269,30779521,CC BY,"BACKGROUND: The CDC hosts monthly panel presentations titled ‘Public Health Grand Rounds’ and publishes monthly reports known as Vital Signs. Hashtags #CDCGrandRounds and #VitalSigns were used to promote them on Twitter. OBJECTIVES: This study quantified the effect of hashtag count, mention count, and URL count and attaching visual cues to #CDCGrandRounds or #VitalSigns tweets on their retweet frequency. METHODS: Through Twitter Search Application Programming Interface, original tweets containing the hashtag #CDCGrandRounds (n = 6,966; April 21, 2011–October 25, 2016) and the hashtag #VitalSigns (n = 15,015; March 19, 2013–October 31, 2016) were retrieved respectively. Negative binomial regression models were applied to each corpus to estimate the associations between retweet frequency and three predictors (hashtag count, mention count, and URL link count). Each corpus was sub-set into cycles (#CDCGrandRounds: n = 58, #VitalSigns: n = 42). We manually coded the 30 tweets with the highest number of retweets for each cycle, whether it contained visual cues (images or videos). Univariable negative binomial regression models were applied to compute the prevalence ratio (PR) of retweet frequency for each cycle, between tweets with and without visual cues. FINDINGS: URL links increased retweet frequency in both corpora; effects of hashtag count and mention count differed between the two corpora. Of the 58 #CDCGrandRounds cycles, 29 were found to have statistically significantly different retweet frequencies between tweets with and without visual cues. Of these 29 cycles, one had a PR estimate < 1; twenty-four, PR > 1 but < 3; and four, PR > 3. Of the 42 #VitalSigns cycles, 19 were statistically significant. Of these 19 cycles, six were PR > 1 and < 3; and thirteen, PR > 3. CONCLUSIONS: The increase of retweet frequency through attaching visual cues varied across cycles for original tweets with #CDCGrandRounds and #VitalSigns. Future research is needed to determine the optimal choice of visual cues to maximize the influence of public health tweets.",,"['Jackson, Ashley M.', 'Mullican, Lindsay A.', 'Yin, Jingjing', 'Ho Tse, Zion Tsz', 'Liang, Hai', 'Fu, King-Wa', 'Ahweyevu, Jennifer O.', 'Jenkins, Jimmy J.', 'Saroha, Nitin', 'Fung, Isaac Chun-Hai']",Ann Glob Health.; 84(4):710-716,,,True
c3d79e1b3bb0159b3c333de43cdff8988bcd459f,PMC,Unified feature association networks through integration of transcriptomic and proteomic data,http://dx.doi.org/10.1371/journal.pcbi.1007241,PMC6748406,31527878,CC0,"High-throughput multi-omics studies and corresponding network analyses of multi-omic data have rapidly expanded their impact over the last 10 years. As biological features of different types (e.g. transcripts, proteins, metabolites) interact within cellular systems, the greatest amount of knowledge can be gained from networks that incorporate multiple types of -omic data. However, biological and technical sources of variation diminish the ability to detect cross-type associations, yielding networks dominated by communities comprised of nodes of the same type. We describe here network building methods that can maximize edges between nodes of different data types leading to integrated networks, networks that have a large number of edges that link nodes of different–omic types (transcripts, proteins, lipids etc). We systematically rank several network inference methods and demonstrate that, in many cases, using a random forest method, GENIE3, produces the most integrated networks. This increase in integration does not come at the cost of accuracy as GENIE3 produces networks of approximately the same quality as the other network inference methods tested here. Using GENIE3, we also infer networks representing antibody-mediated Dengue virus cell invasion and receptor-mediated Dengue virus invasion. A number of functional pathways showed centrality differences between the two networks including genes responding to both GM-CSF and IL-4, which had a higher centrality value in an antibody-mediated vs. receptor-mediated Dengue network. Because a biological system involves the interplay of many different types of molecules, incorporating multiple data types into networks will improve their use as models of biological systems. The methods explored here are some of the first to specifically highlight and address the challenges associated with how such multi-omic networks can be assembled and how the greatest number of interactions can be inferred from different data types. The resulting networks can lead to the discovery of new host response patterns and interactions during viral infection, generate new hypotheses of pathogenic mechanisms and confirm mechanisms of disease.",2019 Sep 17,"['McClure, Ryan S.', 'Wendler, Jason P.', 'Adkins, Joshua N.', 'Swanstrom, Jesica', 'Baric, Ralph', 'Kaiser, Brooke L. Deatherage', 'Oxford, Kristie L.', 'Waters, Katrina M.', 'McDermott, Jason E.']",PLoS Comput Biol,,,True
1d04a005878128bea0e61ac7312b7ebbde138f2b,PMC,Unified feature association networks through integration of transcriptomic and proteomic data,http://dx.doi.org/10.1371/journal.pcbi.1007241,PMC6748406,31527878,CC0,"High-throughput multi-omics studies and corresponding network analyses of multi-omic data have rapidly expanded their impact over the last 10 years. As biological features of different types (e.g. transcripts, proteins, metabolites) interact within cellular systems, the greatest amount of knowledge can be gained from networks that incorporate multiple types of -omic data. However, biological and technical sources of variation diminish the ability to detect cross-type associations, yielding networks dominated by communities comprised of nodes of the same type. We describe here network building methods that can maximize edges between nodes of different data types leading to integrated networks, networks that have a large number of edges that link nodes of different–omic types (transcripts, proteins, lipids etc). We systematically rank several network inference methods and demonstrate that, in many cases, using a random forest method, GENIE3, produces the most integrated networks. This increase in integration does not come at the cost of accuracy as GENIE3 produces networks of approximately the same quality as the other network inference methods tested here. Using GENIE3, we also infer networks representing antibody-mediated Dengue virus cell invasion and receptor-mediated Dengue virus invasion. A number of functional pathways showed centrality differences between the two networks including genes responding to both GM-CSF and IL-4, which had a higher centrality value in an antibody-mediated vs. receptor-mediated Dengue network. Because a biological system involves the interplay of many different types of molecules, incorporating multiple data types into networks will improve their use as models of biological systems. The methods explored here are some of the first to specifically highlight and address the challenges associated with how such multi-omic networks can be assembled and how the greatest number of interactions can be inferred from different data types. The resulting networks can lead to the discovery of new host response patterns and interactions during viral infection, generate new hypotheses of pathogenic mechanisms and confirm mechanisms of disease.",2019 Sep 17,"['McClure, Ryan S.', 'Wendler, Jason P.', 'Adkins, Joshua N.', 'Swanstrom, Jesica', 'Baric, Ralph', 'Kaiser, Brooke L. Deatherage', 'Oxford, Kristie L.', 'Waters, Katrina M.', 'McDermott, Jason E.']",PLoS Comput Biol,,,False
21032ff125f6da6316b1b686223393fd5286d8bd,PMC,Unified feature association networks through integration of transcriptomic and proteomic data,http://dx.doi.org/10.1371/journal.pcbi.1007241,PMC6748406,31527878,CC0,"High-throughput multi-omics studies and corresponding network analyses of multi-omic data have rapidly expanded their impact over the last 10 years. As biological features of different types (e.g. transcripts, proteins, metabolites) interact within cellular systems, the greatest amount of knowledge can be gained from networks that incorporate multiple types of -omic data. However, biological and technical sources of variation diminish the ability to detect cross-type associations, yielding networks dominated by communities comprised of nodes of the same type. We describe here network building methods that can maximize edges between nodes of different data types leading to integrated networks, networks that have a large number of edges that link nodes of different–omic types (transcripts, proteins, lipids etc). We systematically rank several network inference methods and demonstrate that, in many cases, using a random forest method, GENIE3, produces the most integrated networks. This increase in integration does not come at the cost of accuracy as GENIE3 produces networks of approximately the same quality as the other network inference methods tested here. Using GENIE3, we also infer networks representing antibody-mediated Dengue virus cell invasion and receptor-mediated Dengue virus invasion. A number of functional pathways showed centrality differences between the two networks including genes responding to both GM-CSF and IL-4, which had a higher centrality value in an antibody-mediated vs. receptor-mediated Dengue network. Because a biological system involves the interplay of many different types of molecules, incorporating multiple data types into networks will improve their use as models of biological systems. The methods explored here are some of the first to specifically highlight and address the challenges associated with how such multi-omic networks can be assembled and how the greatest number of interactions can be inferred from different data types. The resulting networks can lead to the discovery of new host response patterns and interactions during viral infection, generate new hypotheses of pathogenic mechanisms and confirm mechanisms of disease.",2019 Sep 17,"['McClure, Ryan S.', 'Wendler, Jason P.', 'Adkins, Joshua N.', 'Swanstrom, Jesica', 'Baric, Ralph', 'Kaiser, Brooke L. Deatherage', 'Oxford, Kristie L.', 'Waters, Katrina M.', 'McDermott, Jason E.']",PLoS Comput Biol,,,False
cb24b5df5b00bf7704179b5ceef7a76861a25732,PMC,Unified feature association networks through integration of transcriptomic and proteomic data,http://dx.doi.org/10.1371/journal.pcbi.1007241,PMC6748406,31527878,CC0,"High-throughput multi-omics studies and corresponding network analyses of multi-omic data have rapidly expanded their impact over the last 10 years. As biological features of different types (e.g. transcripts, proteins, metabolites) interact within cellular systems, the greatest amount of knowledge can be gained from networks that incorporate multiple types of -omic data. However, biological and technical sources of variation diminish the ability to detect cross-type associations, yielding networks dominated by communities comprised of nodes of the same type. We describe here network building methods that can maximize edges between nodes of different data types leading to integrated networks, networks that have a large number of edges that link nodes of different–omic types (transcripts, proteins, lipids etc). We systematically rank several network inference methods and demonstrate that, in many cases, using a random forest method, GENIE3, produces the most integrated networks. This increase in integration does not come at the cost of accuracy as GENIE3 produces networks of approximately the same quality as the other network inference methods tested here. Using GENIE3, we also infer networks representing antibody-mediated Dengue virus cell invasion and receptor-mediated Dengue virus invasion. A number of functional pathways showed centrality differences between the two networks including genes responding to both GM-CSF and IL-4, which had a higher centrality value in an antibody-mediated vs. receptor-mediated Dengue network. Because a biological system involves the interplay of many different types of molecules, incorporating multiple data types into networks will improve their use as models of biological systems. The methods explored here are some of the first to specifically highlight and address the challenges associated with how such multi-omic networks can be assembled and how the greatest number of interactions can be inferred from different data types. The resulting networks can lead to the discovery of new host response patterns and interactions during viral infection, generate new hypotheses of pathogenic mechanisms and confirm mechanisms of disease.",2019 Sep 17,"['McClure, Ryan S.', 'Wendler, Jason P.', 'Adkins, Joshua N.', 'Swanstrom, Jesica', 'Baric, Ralph', 'Kaiser, Brooke L. Deatherage', 'Oxford, Kristie L.', 'Waters, Katrina M.', 'McDermott, Jason E.']",PLoS Comput Biol,,,False
1c3c2971529e388109209c0faede439591465380,PMC,Unified feature association networks through integration of transcriptomic and proteomic data,http://dx.doi.org/10.1371/journal.pcbi.1007241,PMC6748406,31527878,CC0,"High-throughput multi-omics studies and corresponding network analyses of multi-omic data have rapidly expanded their impact over the last 10 years. As biological features of different types (e.g. transcripts, proteins, metabolites) interact within cellular systems, the greatest amount of knowledge can be gained from networks that incorporate multiple types of -omic data. However, biological and technical sources of variation diminish the ability to detect cross-type associations, yielding networks dominated by communities comprised of nodes of the same type. We describe here network building methods that can maximize edges between nodes of different data types leading to integrated networks, networks that have a large number of edges that link nodes of different–omic types (transcripts, proteins, lipids etc). We systematically rank several network inference methods and demonstrate that, in many cases, using a random forest method, GENIE3, produces the most integrated networks. This increase in integration does not come at the cost of accuracy as GENIE3 produces networks of approximately the same quality as the other network inference methods tested here. Using GENIE3, we also infer networks representing antibody-mediated Dengue virus cell invasion and receptor-mediated Dengue virus invasion. A number of functional pathways showed centrality differences between the two networks including genes responding to both GM-CSF and IL-4, which had a higher centrality value in an antibody-mediated vs. receptor-mediated Dengue network. Because a biological system involves the interplay of many different types of molecules, incorporating multiple data types into networks will improve their use as models of biological systems. The methods explored here are some of the first to specifically highlight and address the challenges associated with how such multi-omic networks can be assembled and how the greatest number of interactions can be inferred from different data types. The resulting networks can lead to the discovery of new host response patterns and interactions during viral infection, generate new hypotheses of pathogenic mechanisms and confirm mechanisms of disease.",2019 Sep 17,"['McClure, Ryan S.', 'Wendler, Jason P.', 'Adkins, Joshua N.', 'Swanstrom, Jesica', 'Baric, Ralph', 'Kaiser, Brooke L. Deatherage', 'Oxford, Kristie L.', 'Waters, Katrina M.', 'McDermott, Jason E.']",PLoS Comput Biol,,,False
0f1112e84d127f4db891c80121ba634c08793186,PMC,Unified feature association networks through integration of transcriptomic and proteomic data,http://dx.doi.org/10.1371/journal.pcbi.1007241,PMC6748406,31527878,CC0,"High-throughput multi-omics studies and corresponding network analyses of multi-omic data have rapidly expanded their impact over the last 10 years. As biological features of different types (e.g. transcripts, proteins, metabolites) interact within cellular systems, the greatest amount of knowledge can be gained from networks that incorporate multiple types of -omic data. However, biological and technical sources of variation diminish the ability to detect cross-type associations, yielding networks dominated by communities comprised of nodes of the same type. We describe here network building methods that can maximize edges between nodes of different data types leading to integrated networks, networks that have a large number of edges that link nodes of different–omic types (transcripts, proteins, lipids etc). We systematically rank several network inference methods and demonstrate that, in many cases, using a random forest method, GENIE3, produces the most integrated networks. This increase in integration does not come at the cost of accuracy as GENIE3 produces networks of approximately the same quality as the other network inference methods tested here. Using GENIE3, we also infer networks representing antibody-mediated Dengue virus cell invasion and receptor-mediated Dengue virus invasion. A number of functional pathways showed centrality differences between the two networks including genes responding to both GM-CSF and IL-4, which had a higher centrality value in an antibody-mediated vs. receptor-mediated Dengue network. Because a biological system involves the interplay of many different types of molecules, incorporating multiple data types into networks will improve their use as models of biological systems. The methods explored here are some of the first to specifically highlight and address the challenges associated with how such multi-omic networks can be assembled and how the greatest number of interactions can be inferred from different data types. The resulting networks can lead to the discovery of new host response patterns and interactions during viral infection, generate new hypotheses of pathogenic mechanisms and confirm mechanisms of disease.",2019 Sep 17,"['McClure, Ryan S.', 'Wendler, Jason P.', 'Adkins, Joshua N.', 'Swanstrom, Jesica', 'Baric, Ralph', 'Kaiser, Brooke L. Deatherage', 'Oxford, Kristie L.', 'Waters, Katrina M.', 'McDermott, Jason E.']",PLoS Comput Biol,,,False
464765a7fdf94667eef4c09b6ea35a043e3cec7d,PMC,Unified feature association networks through integration of transcriptomic and proteomic data,http://dx.doi.org/10.1371/journal.pcbi.1007241,PMC6748406,31527878,CC0,"High-throughput multi-omics studies and corresponding network analyses of multi-omic data have rapidly expanded their impact over the last 10 years. As biological features of different types (e.g. transcripts, proteins, metabolites) interact within cellular systems, the greatest amount of knowledge can be gained from networks that incorporate multiple types of -omic data. However, biological and technical sources of variation diminish the ability to detect cross-type associations, yielding networks dominated by communities comprised of nodes of the same type. We describe here network building methods that can maximize edges between nodes of different data types leading to integrated networks, networks that have a large number of edges that link nodes of different–omic types (transcripts, proteins, lipids etc). We systematically rank several network inference methods and demonstrate that, in many cases, using a random forest method, GENIE3, produces the most integrated networks. This increase in integration does not come at the cost of accuracy as GENIE3 produces networks of approximately the same quality as the other network inference methods tested here. Using GENIE3, we also infer networks representing antibody-mediated Dengue virus cell invasion and receptor-mediated Dengue virus invasion. A number of functional pathways showed centrality differences between the two networks including genes responding to both GM-CSF and IL-4, which had a higher centrality value in an antibody-mediated vs. receptor-mediated Dengue network. Because a biological system involves the interplay of many different types of molecules, incorporating multiple data types into networks will improve their use as models of biological systems. The methods explored here are some of the first to specifically highlight and address the challenges associated with how such multi-omic networks can be assembled and how the greatest number of interactions can be inferred from different data types. The resulting networks can lead to the discovery of new host response patterns and interactions during viral infection, generate new hypotheses of pathogenic mechanisms and confirm mechanisms of disease.",2019 Sep 17,"['McClure, Ryan S.', 'Wendler, Jason P.', 'Adkins, Joshua N.', 'Swanstrom, Jesica', 'Baric, Ralph', 'Kaiser, Brooke L. Deatherage', 'Oxford, Kristie L.', 'Waters, Katrina M.', 'McDermott, Jason E.']",PLoS Comput Biol,,,False
59c8102df7576491106a5423d315e2f026e5085c,PMC,Unified feature association networks through integration of transcriptomic and proteomic data,http://dx.doi.org/10.1371/journal.pcbi.1007241,PMC6748406,31527878,CC0,"High-throughput multi-omics studies and corresponding network analyses of multi-omic data have rapidly expanded their impact over the last 10 years. As biological features of different types (e.g. transcripts, proteins, metabolites) interact within cellular systems, the greatest amount of knowledge can be gained from networks that incorporate multiple types of -omic data. However, biological and technical sources of variation diminish the ability to detect cross-type associations, yielding networks dominated by communities comprised of nodes of the same type. We describe here network building methods that can maximize edges between nodes of different data types leading to integrated networks, networks that have a large number of edges that link nodes of different–omic types (transcripts, proteins, lipids etc). We systematically rank several network inference methods and demonstrate that, in many cases, using a random forest method, GENIE3, produces the most integrated networks. This increase in integration does not come at the cost of accuracy as GENIE3 produces networks of approximately the same quality as the other network inference methods tested here. Using GENIE3, we also infer networks representing antibody-mediated Dengue virus cell invasion and receptor-mediated Dengue virus invasion. A number of functional pathways showed centrality differences between the two networks including genes responding to both GM-CSF and IL-4, which had a higher centrality value in an antibody-mediated vs. receptor-mediated Dengue network. Because a biological system involves the interplay of many different types of molecules, incorporating multiple data types into networks will improve their use as models of biological systems. The methods explored here are some of the first to specifically highlight and address the challenges associated with how such multi-omic networks can be assembled and how the greatest number of interactions can be inferred from different data types. The resulting networks can lead to the discovery of new host response patterns and interactions during viral infection, generate new hypotheses of pathogenic mechanisms and confirm mechanisms of disease.",2019 Sep 17,"['McClure, Ryan S.', 'Wendler, Jason P.', 'Adkins, Joshua N.', 'Swanstrom, Jesica', 'Baric, Ralph', 'Kaiser, Brooke L. Deatherage', 'Oxford, Kristie L.', 'Waters, Katrina M.', 'McDermott, Jason E.']",PLoS Comput Biol,,,False
3cbc04dc1d9cc8faffc2328df66ac20e09e93661,PMC,"Science, innovation and society: what we need to prepare for the health challenges of the twenty-first century?",http://dx.doi.org/10.1093/inthealth/ihz047,PMC6748718,31529109,CC BY,,2019 Sep 1,"Farrar, Jeremy",Int Health,,,True
d926927a6087c2e98e431d68a7a457844a5edc0d,PMC,Cost-Effectiveness Analysis of Influenza A (H1N1) Chemoprophylaxis in Brazil,http://dx.doi.org/10.3389/fphar.2019.00945,PMC6749104,31572172,CC BY,"Background: Oseltamivir and zanamivir are recommended for treating and preventing influenza A (H1N1) worldwide. In Brazil, this official recommendation lacks an economic evaluation. Our objective was to assess the efficiency of influenza A chemoprophylaxis in the Brazilian context. Methods: We assessed the cost-effectiveness of oseltamivir and zanamivir for prophylaxis of influenza for high risk population, compared to no prophylaxis, in the perspective of Brazilian public health system. Quality-adjusted life years (QALY) and effectiveness data were based on literature review and costs in Brazilian real (BRL) were estimated from official sources and micro-costing of 2016’s H1N1 admissions at a university hospital. We used a decision-tree model considering prophylaxis and no prophylaxis and the probabilities of H1N1, ambulatory care, admission to hospital, intensive care, patient discharge, and death. Adherence and adverse events from prophylaxis were included. Incremental cost-effectiveness ratio was converted to 2016 United States dollar (USD). Uncertainty was assessed with univariated and probabilistic sensitivity analysis. Results: Adherence to prophylaxis was 0.70 [95% confidence interval (CI) 0.54; 0.83]; adverse events, 0.09 (95% CI 0.02; 0.18); relative risk of H1N1 infection in chemoprophylaxis, 0.43 (95% CI 0.33; 0.57); incidence of H1N1, 0.14 (95% CI 0.11; 0.16); ambulatory care, 0.67 (95% CI 0.58; 0.75); hospital admission, 0.43 (CI 95% 0.39; 0.42); hospital mortality, 0.14 (CI 95% 0.12; 0.15); intensive care unit admission, 0.23 (95% CI 0.20; 0.27); and intensive care mortality, 0.40 (95% CI 0.29; 0.52). QALY in H1N1 state was 0.50 (95% CI 0.46; 0.53); in H1N1 inpatients, 0.23 (95% CI 0.18; 0.28); healthy, 0.885 (95% CI 0.879; 0.891); death, 0. Adverse events estimated to affect QALY in –0.185 (95% CI –0.290; –0.050). Cost for chemoprophylaxis was BRL 39.42 [standard deviation (SD) 17.94]; ambulatory care, BRL 12.47 (SD 5.21); hospital admission, BRL 5,727.59 (SD 7,758.28); intensive care admission, BRL 19,217.25 (SD 7,917.33); and adverse events, BRL 292.05 (SD 724.95). Incremental cost-effectiveness ratio was BRL –4,080.63 (USD –1,263.74)/QALY and –982.39 (USD –304.24)/H1N1 prevented. Results were robust to sensitivity analysis. Conclusion: Chemoprophylaxis of influenza A (H1N1) is cost-saving in Brazilian health system context.",2019 Sep 10,"['Vecoso, Luisa von Zuben', 'Silva, Marcus Tolentino', 'Resende, Mariangela Ribeiro', 'da Silva, Everton Nunes', 'Galvao, Tais Freire']",Front Pharmacol,,,False
e7e38adcd3016f0375633fd4d989c8016959484c,PMC,Cost-Effectiveness Analysis of Influenza A (H1N1) Chemoprophylaxis in Brazil,http://dx.doi.org/10.3389/fphar.2019.00945,PMC6749104,31572172,CC BY,"Background: Oseltamivir and zanamivir are recommended for treating and preventing influenza A (H1N1) worldwide. In Brazil, this official recommendation lacks an economic evaluation. Our objective was to assess the efficiency of influenza A chemoprophylaxis in the Brazilian context. Methods: We assessed the cost-effectiveness of oseltamivir and zanamivir for prophylaxis of influenza for high risk population, compared to no prophylaxis, in the perspective of Brazilian public health system. Quality-adjusted life years (QALY) and effectiveness data were based on literature review and costs in Brazilian real (BRL) were estimated from official sources and micro-costing of 2016’s H1N1 admissions at a university hospital. We used a decision-tree model considering prophylaxis and no prophylaxis and the probabilities of H1N1, ambulatory care, admission to hospital, intensive care, patient discharge, and death. Adherence and adverse events from prophylaxis were included. Incremental cost-effectiveness ratio was converted to 2016 United States dollar (USD). Uncertainty was assessed with univariated and probabilistic sensitivity analysis. Results: Adherence to prophylaxis was 0.70 [95% confidence interval (CI) 0.54; 0.83]; adverse events, 0.09 (95% CI 0.02; 0.18); relative risk of H1N1 infection in chemoprophylaxis, 0.43 (95% CI 0.33; 0.57); incidence of H1N1, 0.14 (95% CI 0.11; 0.16); ambulatory care, 0.67 (95% CI 0.58; 0.75); hospital admission, 0.43 (CI 95% 0.39; 0.42); hospital mortality, 0.14 (CI 95% 0.12; 0.15); intensive care unit admission, 0.23 (95% CI 0.20; 0.27); and intensive care mortality, 0.40 (95% CI 0.29; 0.52). QALY in H1N1 state was 0.50 (95% CI 0.46; 0.53); in H1N1 inpatients, 0.23 (95% CI 0.18; 0.28); healthy, 0.885 (95% CI 0.879; 0.891); death, 0. Adverse events estimated to affect QALY in –0.185 (95% CI –0.290; –0.050). Cost for chemoprophylaxis was BRL 39.42 [standard deviation (SD) 17.94]; ambulatory care, BRL 12.47 (SD 5.21); hospital admission, BRL 5,727.59 (SD 7,758.28); intensive care admission, BRL 19,217.25 (SD 7,917.33); and adverse events, BRL 292.05 (SD 724.95). Incremental cost-effectiveness ratio was BRL –4,080.63 (USD –1,263.74)/QALY and –982.39 (USD –304.24)/H1N1 prevented. Results were robust to sensitivity analysis. Conclusion: Chemoprophylaxis of influenza A (H1N1) is cost-saving in Brazilian health system context.",2019 Sep 10,"['Vecoso, Luisa von Zuben', 'Silva, Marcus Tolentino', 'Resende, Mariangela Ribeiro', 'da Silva, Everton Nunes', 'Galvao, Tais Freire']",Front Pharmacol,,,True
9d82ed9e4eab5525576c427521c25aca625ecd59,PMC,Probing the Effects of Pyrimidine Functional Group Switches on Acyclic Fleximer Analogues for Antiviral Activity,http://dx.doi.org/10.3390/molecules24173184,PMC6749450,31480658,CC BY,"Due to their ability to inhibit viral DNA or RNA replication, nucleoside analogues have been used for decades as potent antiviral therapeutics. However, one of the major limitations of nucleoside analogues is the development of antiviral resistance. In that regard, flexible nucleoside analogues known as “fleximers” have garnered attention over the years due to their ability to survey different amino acids in enzyme binding sites, thus overcoming the potential development of antiviral resistance. Acyclic fleximers have previously demonstrated antiviral activity against numerous viruses including Middle East Respiratory Syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and, most recently, flaviviruses such as Dengue (DENV) and Yellow Fever Virus (YFV). Due to these interesting results, a Structure Activity Relationship (SAR) study was pursued in order to analyze the effect of the pyrimidine functional group and acyl protecting group on antiviral activity, cytotoxicity, and conformation. The results of those studies are presented herein.",2019 Sep 2,"['Yates, Mary K.', 'Chatterjee, Payel', 'Flint, Mike', 'Arefeayne, Yafet', 'Makuc, Damjan', 'Plavec, Janez', 'Spiropoulou, Christina F.', 'Seley-Radtke, Katherine L.']",Molecules,,,True
53ef9e00b8d6b8575d2e7dd68b840f487b24c5a2,PMC,Assessing exhibition swine as potential disseminators of infectious disease through the detection of five respiratory pathogens at agricultural exhibitions,http://dx.doi.org/10.1186/s13567-019-0684-5,PMC6749708,31533860,CC BY,"Widespread geographic movement and extensive comingling of exhibition swine facilitates the spread and transmission of infectious pathogens. Nasal samples were collected from 2862 pigs at 102 exhibitions and tested for five pathogens. At least one pathogen was molecularly detected in pigs at 63 (61.8%) exhibitions. Influenza A virus was most prevalent and was detected in 498 (17.4%) samples. Influenza D virus was detected in two (0.07%) samples. More than one pathogen was detected in 165 (5.8%) samples. Influenza A virus remains a top threat to animal and human health, but other pathogens may be disseminated through the exhibition swine population.",2019 Sep 18,"['Lauterbach, Sarah E.', 'Nelson, Sarah W.', 'Robinson, Meghann E.', 'Lorbach, Josh N.', 'Nolting, Jacqueline M.', 'Bowman, Andrew S.']",Vet Res,,,True
8b8eca79a2c4625f1ebc17b342a1755253ba473f,PMC,A Coding Sequence-Embedded Principle Governs Translational Reading Frame Fidelity,http://dx.doi.org/10.1155/2018/7089174,PMC6750092,31549036,CC BY,"Upon initiation at a start codon, the ribosome must maintain the correct reading frame for hundreds of codons in order to produce functional proteins. While some sequence elements are able to trigger programmed ribosomal frameshifting (PRF), very little is known about how the ribosome normally prevents spontaneous frameshift errors that can have dire consequences if uncorrected. Using high resolution ribosome profiling data sets, we discovered that the translating ribosome uses the 3′ end of 18S rRNA to scan the AUG-like codons after the decoding process. The postdecoding mRNA:rRNA interaction not only contributes to predominant translational pausing, but also provides a retrospective mechanism to safeguard the ribosome in the correct reading frame. Partially eliminating the AUG-like “sticky” codons in the reporter message leads to increased +1 frameshift errors. Remarkably, mutating the highly conserved CAU triplet of 18S rRNA globally changes the codon “stickiness”. Further supporting the role of “sticky” sequences in reading frame maintenance, the codon composition of open reading frames is highly optimized across eukaryotic genomes. These results suggest an important layer of information embedded within the protein-coding sequences that instructs the ribosome to ensure reading frame fidelity during translation.",2018 Sep 20,"['Wan, Ji', 'Gao, Xiangwei', 'Mao, Yuanhui', 'Zhang, Xingqian', 'Qian, Shu-Bing']",Research (Wash D C),,,True
1dd7096290bcbcc5aa830706c5396155ef51bd39,PMC,Situations Leading to Reduced Effectiveness of Current Hand Hygiene against Infectious Mucus from Influenza Virus-Infected Patients,http://dx.doi.org/10.1128/mSphere.00474-19,PMC6751490,31533996,CC BY,"Both antiseptic hand rubbing (AHR) using ethanol-based disinfectants (EBDs) and antiseptic hand washing (AHW) are important means of infection control to prevent seasonal influenza A virus (IAV) outbreaks. However, previous reports suggest a reduced efficacy of ethanol disinfection against pathogens in mucus. We aimed to elucidate the situations and mechanisms underlying the reduced efficacy of EBDs against IAV in infectious mucus. We evaluated IAV inactivation and ethanol concentration change using IAV-infected patients’ mucus (sputum). Additionally, AHR and AHW effectiveness against infectious mucus adhering to the hands and fingers was evaluated in 10 volunteers. Our clinical study showed that EBD effectiveness against IAV in mucus was extremely reduced compared to IAV in saline. IAV in mucus remained active despite 120 s of AHR; however, IAV in saline was completely inactivated within 30 s. Due to the low rate of diffusion/convection because of the physical properties of mucus as a hydrogel, the time required for the ethanol concentration to reach an IAV inactivation level and thus for EBDs to completely inactivate IAV was approximately eight times longer in mucus than in saline. On the other hand, AHR inactivated IAV in mucus within 30 s when the mucus dried completely because the hydrogel characteristics were lost. Additionally, AHW rapidly inactivated IAV. Until infectious mucus has completely dried, infectious IAV can remain on the hands and fingers, even after appropriate AHR using EBD, thereby increasing the risk of IAV transmission. We clarified the ineffectiveness of EBD use against IAV in infectious mucus. IMPORTANCE Antiseptic hand rubbing (AHR) and antiseptic hand washing (AHW) are important to prevent the spread of influenza A virus (IAV). This study elucidated the situations/mechanisms underlying the reduced efficacy of AHR against infectious mucus derived from IAV-infected individuals and indicated the weaknesses of the current hand hygiene regimens. Due to the low rate of diffusion/convection because of the physical properties of mucus as a hydrogel, the efficacy of AHR using ethanol-based disinfectant against mucus is greatly reduced until infectious mucus adhering to the hands/fingers has completely dried. If there is insufficient time before treating the next patient (i.e., if the infectious mucus is not completely dry), medical staff should be aware that effectiveness of AHR is reduced. Since AHW is effective against both dry and nondry infectious mucus, AHW should be adopted to compensate for these weaknesses of AHR.",2019 Sep 18,"['Hirose, Ryohei', 'Nakaya, Takaaki', 'Naito, Yuji', 'Daidoji, Tomo', 'Bandou, Risa', 'Inoue, Ken', 'Dohi, Osamu', 'Yoshida, Naohisa', 'Konishi, Hideyuki', 'Itoh, Yoshito']",mSphere,,,True
eb02e66bf6c521ac15b2dfa14b2b7966f137c876,PMC,"Detecting influenza and emerging avian influenza virus by influenza and pneumonia surveillance systems in a large city in China, 2005 to 2016",http://dx.doi.org/10.1186/s12879-019-4405-5,PMC6751661,31533638,CC BY,"BACKGROUND: Detecting avian influenza virus has become an important public health strategy for controlling the emerging infectious disease. METHODS: The HIS (hospital information system) modified influenza surveillance system (ISS) and a newly built pneumonia surveillance system (PSS) were used to monitor the influenza viruses in Changsha City, China. The ISS was used to monitor outpatients in two sentinel hospitals and to detect mild influenza and avian influenza cases, and PSS was used to monitor inpatients in 49 hospitals and to detect severe and death influenza cases. RESULTS: From 2005 to 2016, there were 3,551,917 outpatients monitored by the ISS system, among whom 126,076 were influenza-like illness (ILI) cases, with the ILI proportion (ILI%) of 3.55%. After the HIS was used, the reported incident cases of ILI and ILI% were increased significantly. From March, 2009 to September, 2016, there were 5,491,560 inpatient cases monitored by the PSS system, among which 362,743 were pneumonia cases, with a proportion of 6.61%. Among pneumonia cases, about 10.55% (38,260/362,743) of cases were severe or death cases. The pneumonia incidence increased each year in the city. Among 15 avian influenza cases reported from January, 2005 to September, 2016, there were 26.7% (4/15) mild cases detected by the HIS-modified ISS system, while 60.0% (9/15) were severe or death cases detected by the PSS system. Two H5N1 severe cases were missed by the ISS system in January, 2009 when the PSS system was not available. CONCLUSIONS: The HIS was able to improve the efficiency of the ISS for monitoring ILI and emerging avian influenza virus. However, the efficiency of the system needs to be verified in a wider area for a longer time span in China.",2019 Sep 18,"['Guo, Xiaorong', 'Yang, Dong', 'Liu, Ruchun', 'Li, Yaman', 'Hu, Qingqing', 'Ma, Xinrui', 'Li, Yelan', 'Zhang, Heng', 'Zhang, Xixing', 'Zhao, Benhua', 'Chen, Tianmu']",BMC Infect Dis,,,True
0d5f9dd2c1626d1d3a4228b838fc0bc666363a3c,PMC,Peptide presentation by bat MHC class I provides new insight into the antiviral immunity of bats,http://dx.doi.org/10.1371/journal.pbio.3000436,PMC6752855,31498797,CC BY,"Bats harbor many zoonotic viruses, including highly pathogenic viruses of humans and other mammals, but they are typically asymptomatic in bats. To further understand the antiviral immunity of bats, we screened and identified a series of bat major histocompatibility complex (MHC) I Ptal-N*01:01–binding peptides derived from four different bat-borne viruses, i.e., Hendra virus (HeV), Ebola virus (EBOV), Middle East respiratory syndrome coronavirus (MERS-CoV), and H17N10 influenza-like virus. The structures of Ptal-N*01:01 display unusual peptide presentation features in that the bat-specific 3–amino acid (aa) insertion enables the tight “surface anchoring” of the P1-Asp in pocket A of bat MHC I. As the classical primary anchoring positions, the B and F pockets of Ptal-N*01:01 also show unconventional conformations, which contribute to unusual peptide motifs and distinct peptide presentation. Notably, the features of bat MHC I may be shared by MHC I from various marsupials. Our study sheds light on bat adaptive immunity and may benefit future vaccine development against bat-borne viruses of high impact on humans.",2019 Sep 9,"['Lu, Dan', 'Liu, Kefang', 'Zhang, Di', 'Yue, Can', 'Lu, Qiong', 'Cheng, Hao', 'Wang, Liang', 'Chai, Yan', 'Qi, Jianxun', 'Wang, Lin-Fa', 'Gao, George F.', 'Liu, William J.']",PLoS Biol,,,True
89a7453ca8998a3018064029e6c9d6d8db6b513d,PMC,Advances in Diagnostic Approaches for Viral Etiologies of Diarrhea: From the Lab to the Field,http://dx.doi.org/10.3389/fmicb.2019.01957,PMC6758846,31608017,CC BY,"The applications of correct diagnostic approaches play a decisive role in timely containment of infectious diseases spread and mitigation of public health risks. Nevertheless, there is a need to update the diagnostics regularly to capture the new, emergent, and highly divergent viruses. Acute gastroenteritis of viral origin has been identified as a significant cause of mortality across the globe, with the more serious consequences seen at the extremes of age groups (young and elderly) and immune-compromised individuals. Therefore, significant advancements and efforts have been put in the development of enteric virus diagnostics to meet the WHO ASSURED criteria as a benchmark over the years. The Enzyme-Linked Immunosorbent (ELISA) and Polymerase Chain Reaction (PCR) are the basic assays that provided the platform for development of several efficient diagnostics such as real-time RT-PCR, loop-mediated isothermal amplification (LAMP), polymerase spiral reaction (PSR), biosensors, microarrays and next generation sequencing. Herein, we describe and discuss the applications of these advanced technologies in context to enteric virus detection by delineating their features, advantages and limitations.",2019 Sep 13,"['Malik, Yashpal Singh', 'Verma, Atul Kumar', 'Kumar, Naveen', 'Touil, Nadia', 'Karthik, Kumaragurubaran', 'Tiwari, Ruchi', 'Bora, Durlav Prasad', 'Dhama, Kuldeep', 'Ghosh, Souvik', 'Hemida, Maged Gomaa', 'Abdel-Moneim, Ahmed S.', 'Bányai, Krisztián', 'Vlasova, Anastasia N.', 'Kobayashi, Nobumichi', 'Singh, Raj Kumar']",Front Microbiol,,,True
f1d456ea268266ff3c21317c4190e4fcb49b5e4f,PMC,Gastroenteritis and respiratory infection outbreaks in French nursing homes from 2007 to 2018: Morbidity and all-cause lethality according to the individual characteristics of residents,http://dx.doi.org/10.1371/journal.pone.0222321,PMC6759171,31550261,CC BY,"BACKGROUND: Gastroenteritis (GE) and respiratory tract infection (RTI) outbreaks are a significant issue in nursing homes. This study aimed to describe GE and RTI outbreaks with infection and all-cause lethality rates according to the individual characteristics of nursing home residents. METHODS: Clinical and virological surveillance were conducted (2007 to 2018). Virus stratifications for the analysis were: outbreaks with positive norovirus or influenza identifications (respectively NoV+ or Flu+), episodes with no NoV or influenza identification or testing (respectively NoV- or Flu-). Associations between individual variables (sex, age, length of stay (LOS), autonomy status) and infection and lethality rates were tested with univariate and Mantel-Haenszel (MH) methods. RESULTS: 61 GE outbreaks and 76 RTI oubreaks (total 137 outbreaks) were recorded involving respectively 4309 and 5862 residents. In univariate analysis, higher infection rates and age were associated in NoV+, NoV-, and Flu+ contexts, and lower infection rates were associated with longer stays (NoV+ and NoV-). In MH stratified analysis (virus, sex (female/male)) adjusted for LOS (<4 or ≥4 years), the odds of being infected remained significant among older residents (≥86 years): NoV+/male (Odds ratio (OR(MH)): 1.64, 95% confidence interval (CI): 1.16–2.30) and Flu+/female and male (respectively OR(MH): 1.50, CI: 1.27–1.79 and 1.73, CI: 1.28–2.33). In univariate analysis, lower autonomy status (NoV+, Flu+ and Flu-) and increased age (Flu+) were associated with higher lethality. In MH adjusted analysis, significant OR(age) adjusted for autonomy was: Flu+/ ≥86 years compared with <86 years, 1.97 (1.19–3.25) and OR(autonomy) adjusted for age for the more autonomous group (compared with the less autonomous group) was: Flu+, 0.41 (0.24–0.69); Flu-, 0.42 (0.20, 0.90). CONCLUSION: The residents of nursing homes are increasingly elderly and dependent. The specific infection and lethality risks according to these two factors indicate that surveillance and infection control measures are essential and of high priority.",2019 Sep 24,"['Gaspard, Philippe', 'Mosnier, Anne', 'Simon, Loic', 'Ali-Brandmeyer, Olivia', 'Rabaud, Christian', 'Larocca, Sabrina', 'Heck, Béatrice', 'Aho-Glélé, Serge', 'Pothier, Pierre', 'Ambert-Balay, Katia']",PLoS One,,,True
c8319e7c2950df8028c8b9d90581eff5e13df132,PMC,Uptake of Recommended Vaccines and Its Associated Factors Among Malaysian Pilgrims During Hajj and Umrah 2018,http://dx.doi.org/10.3389/fpubh.2019.00268,PMC6759542,31620419,CC BY,"This study aimed to assess the uptake of recommended vaccines and to identify the factors associated with the vaccines' uptake among Malaysian Hajj and Umrah pilgrims. A cross-sectional survey among Malaysian Hajj and Umrah pilgrims in 2018. The uptake of the recommended vaccines was surveyed through an anonymous self-administered questionnaire to pilgrims attending a pre-departure Hajj/Umrah orientation course. Descriptive statistics were used for elaborating the demographic characteristics and vaccines uptake of the respondents. Multiple logistic regression was used for predicting the factors associated with the vaccines' uptake. A total of 1,274 pilgrims participated in the study with a mean age (standard deviation) of 42.42 (15.6). A total of 833 (65.4%) participants were females and 232 of the participants (18.2%) had at least more than one chronic disease. The uptake of influenza and pneumococcal vaccines were 28.6% (364/1,274) and 25.4% (324/1,274), respectively. Among the 527 pilgrims who were “at increased risk” of infections, 168 (31.9%) and 184 (34.9%) received influenza and pneumococcal vaccines, respectively. Gender, marital status and occupation were the common predictors associated with vaccines uptake. The vaccination uptake among Malaysian Hajj and Umrah pilgrims is low and declining from previous years. Educating the pilgrims toward vaccine uptake is essential and exploring the barriers for vaccination.",2019 Sep 18,"['Goni, Mohammed Dauda', 'Naing, Nyi Nyi', 'Hasan, Habsah', 'Wan-Arfah, Nadiah', 'Deris, Zakuan Zainy', 'Arifin, Wan Nor', 'Baaba, Aisha Abubakar']",Front Public Health,,,True
86fe86ce31570f771ef1b5f8f8c92a97a9fe22c4,PMC,Opportunities Revealed for Antimicrobial Stewardship and Clinical Practice with Implementation of a Rapid Respiratory Multiplex Assay,http://dx.doi.org/10.1128/JCM.00861-19,PMC6760939,31413077,CC BY,"Few studies assess the utility of rapid multiplex molecular respiratory panels in adult patients. Previous multiplex PCR assays took hours to days from order time to result. We analyze the clinical impact of switching to a molecular assay with a 3-h test-turnaround-time (TAT). We performed a retrospective review of adult patients who presented to our emergency departments with respiratory symptoms and had a respiratory viral panel (xTAG RVP; RVP) or respiratory pathogen panel (ePlex RP; RPP) within 48 h of presentation. The average TATs for the RVP and RPP were 27.9 and 3.0 h, respectively (P < 0.0001). In RVP-positive and RPP-positive patients, 68.9 and 44.5% of those with normal chest imaging received antibiotics (P = 0.013), while 95.4 and 89.6% of those with abnormal imaging received antibiotics, respectively (P = 0.187). There was no difference in antibiotic duration in RVP-positive and RPP-positive patients with abnormal chest imaging (6.2 and 6.0 days, respectively; P = 0.923) and normal chest imaging (4.5 and 4.3 days, respectively; P = 0.922). Fewer patients were admitted in the RPP-positive compared to the RVP-positive group (76.9 and 88.6%, respectively; P = 0.013), while the proportion of admissions were similar among RPP-negative and RVP-negative patients (85.3 and 87.1%, P = 0.726). Switching to a multiplex respiratory panel with a clinically actionable TAT is associated with reduced hospital admissions and, in admitted adults without focal radiographic findings, reduced antibiotic initiation. Opportunities to further mitigate inappropriate antibiotic use may be realized by combining rapid multiplex PCR with provider education, clinical decision-care algorithms, and active antibiotic stewardship.",2019 Sep 24,"['Weiss, Zoe F.', 'Cunha, Cheston B.', 'Chambers, Alison B.', 'Carr, Audrey V.', 'Rochat, Cleo', 'Raglow-Defranco, Mariska', 'Parente, Diane M.', 'Angus, Aimee', 'Mermel, Leonard A.', 'Sivaprasad, Latha', 'Chapin, Kimberle']",J Clin Microbiol,,,True
a335b97a529051e8ff4cbb01ae4ec799ea04651d,PMC,Microbiome-Transcriptome Interactions Related to Severity of Respiratory Syncytial Virus Infection,http://dx.doi.org/10.1038/s41598-019-50217-w,PMC6761288,31554845,CC BY,"Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections and hospital visits during infancy and childhood. Although risk factors for RSV infection have been identified, the role of microbial species in the respiratory tract is only partially known. We aimed to understand the impact of interactions between the nasal microbiome and host transcriptome on the severity and clinical outcomes of RSV infection. We used 16 S rRNA sequencing to characterize the nasal microbiome of infants with RSV infection. We used RNA sequencing to interrogate the transcriptome of CD4(+) T cells obtained from the same set of infants. After dimension reduction through principal component (PC) analysis, we performed an integrative analysis to identify significant co-variation between microbial clade and gene expression PCs. We then employed LIONESS (Linear Interpolation to Obtain Network Estimates for Single Samples) to estimate the clade-gene association patterns for each infant. Our network-based integrative analysis identified several clade-gene associations significantly related to the severity of RSV infection. The microbial taxa with the highest loadings in the implicated clade PCs included Moraxella, Corynebacterium, Streptococcus, Haemophilus influenzae, and Staphylococcus. Interestingly, many of the genes with the highest loadings in the implicated gene PCs are encoded in mitochondrial DNA, while others are involved in the host immune response. This study on microbiome-transcriptome interactions provides insights into how the host immune system mounts a response against RSV and specific infectious agents in nasal microbiota.",2019 Sep 25,"['Sonawane, Abhijeet R.', 'Tian, Liang', 'Chu, Chin-Yi', 'Qiu, Xing', 'Wang, Lu', 'Holden-Wiltse, Jeanne', 'Grier, Alex', 'Gill, Steven R.', 'Caserta, Mary T.', 'Falsey, Ann R.', 'Topham, David J.', 'Walsh, Edward E.', 'Mariani, Thomas J.', 'Weiss, Scott T.', 'Silverman, Edwin K.', 'Glass, Kimberly', 'Liu, Yang-Yu']",Sci Rep,,,False
74af665d4b129e0ed662f50fa0d215f4ff2c2c52,PMC,Microbiome-Transcriptome Interactions Related to Severity of Respiratory Syncytial Virus Infection,http://dx.doi.org/10.1038/s41598-019-50217-w,PMC6761288,31554845,CC BY,"Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections and hospital visits during infancy and childhood. Although risk factors for RSV infection have been identified, the role of microbial species in the respiratory tract is only partially known. We aimed to understand the impact of interactions between the nasal microbiome and host transcriptome on the severity and clinical outcomes of RSV infection. We used 16 S rRNA sequencing to characterize the nasal microbiome of infants with RSV infection. We used RNA sequencing to interrogate the transcriptome of CD4(+) T cells obtained from the same set of infants. After dimension reduction through principal component (PC) analysis, we performed an integrative analysis to identify significant co-variation between microbial clade and gene expression PCs. We then employed LIONESS (Linear Interpolation to Obtain Network Estimates for Single Samples) to estimate the clade-gene association patterns for each infant. Our network-based integrative analysis identified several clade-gene associations significantly related to the severity of RSV infection. The microbial taxa with the highest loadings in the implicated clade PCs included Moraxella, Corynebacterium, Streptococcus, Haemophilus influenzae, and Staphylococcus. Interestingly, many of the genes with the highest loadings in the implicated gene PCs are encoded in mitochondrial DNA, while others are involved in the host immune response. This study on microbiome-transcriptome interactions provides insights into how the host immune system mounts a response against RSV and specific infectious agents in nasal microbiota.",2019 Sep 25,"['Sonawane, Abhijeet R.', 'Tian, Liang', 'Chu, Chin-Yi', 'Qiu, Xing', 'Wang, Lu', 'Holden-Wiltse, Jeanne', 'Grier, Alex', 'Gill, Steven R.', 'Caserta, Mary T.', 'Falsey, Ann R.', 'Topham, David J.', 'Walsh, Edward E.', 'Mariani, Thomas J.', 'Weiss, Scott T.', 'Silverman, Edwin K.', 'Glass, Kimberly', 'Liu, Yang-Yu']",Sci Rep,,,True
e489f92a7fda5ea493642945b61c85b6bde8a76e,PMC,Environmental Contact and Self-contact Patterns of Healthcare Workers: Implications for Infection Prevention and Control,http://dx.doi.org/10.1093/cid/ciz558,PMC6761362,31517975,CC BY,"BACKGROUND: Respiratory viruses on fomites can be transferred to sites susceptible to infection via contact by hands or other fomites. METHODS: Care for hospitalized patients with viral respiratory infections was observed in the patient room for 3-hour periods at an acute care academic medical center for over a 2 year period. One trained observer recorded the healthcare activities performed, contacts with fomites, and self-contacts made by healthcare workers (HCWs), while another observer recorded fomite contacts of patients during the encounter using predefined checklists. RESULTS: The surface contacted by HCWs during the majority of visits was the patient (90%). Environmental surfaces contacted by HCWs frequently during healthcare activities included the tray table (48%), bed surface (41%), bed rail (41%), computer station (37%), and intravenous pole (32%). HCWs touched their own torso and mask in 32% and 29% of the visits, respectively. HCWs’ self-contacts differed significantly among HCW job roles, with providers and respiratory therapists contacting themselves significantly more times than nurses and nurse technicians (P < .05). When HCWs performed only 1 care activity, there were significant differences in the number of patient contacts and self-contacts that HCWs made during performance of multiple care activities (P < .05). CONCLUSIONS: HCWs regularly contact environmental surfaces, patients, and themselves while providing care to patients with infectious diseases, varying among care activities and HCW job roles. These contacts may facilitate the transmission of infection to HCWs and susceptible patients.",2019 Oct 1,"['Phan, Linh T', 'Maita, Dayana', 'Mortiz, Donna C', 'Bleasdale, Susan C', 'Jones, Rachael M']",Clin Infect Dis,,,True
06b07a6407734edcb3af57da5fe2898ba61d1df8,PMC,Evaluation of a Redesigned Personal Protective Equipment Gown,http://dx.doi.org/10.1093/cid/ciz520,PMC6761366,31517973,CC BY,"BACKGROUND: In healthcare, the goal of personal protective equipment (PPE) is to protect healthcare personnel (HCP) and patients from body fluids and infectious organisms via contact, droplet, or airborne transmission. The critical importance of using PPE properly is highlighted by 2 potentially fatal viral infections, severe acute respiratory syndrome–associated coronavirus and Ebola virus, where HCP became infected while caring for patients due to errors in the use of PPE. However, PPE in dealing with less dangerous, but highly infectious organisms is important as well. This work proposes a framework to test and evaluate PPE with a focus on gown design. METHODS: An observational study identified issues with potential for contamination related to gown use. After redesigning the existing gown, a high-fidelity patient simulator study with 40 HCP as participants evaluated the gown redesign using 2 commonly performed tasks. Variables of interest were nonadherence to procedural standards, use problems with the gown during task performance, and usability and cognitive task load ratings of the standard and redesigned gowns. RESULTS: While no differences were found in terms of nonadherence and use problems between the current and the redesigned gown, differences in usability and task load ratings suggested that the redesigned gown is perceived more favorably by HCP. CONCLUSIONS: This work proposes a framework to guide the evaluation of PPE. The results suggest that the current design of the PPE gown can be improved in usability and user satisfaction. Although our data did not find an increase in adherence to protocol when using the redesigned gown, it is likely that higher usability and lower task load could result in higher adherence over longer periods of use.",2019 Oct 1,"['Drews, Frank A', 'Mulvey, Diane', 'Stratford, Kristina', 'Samore, Matthew H', 'Mayer, Jeanmarie']",Clin Infect Dis,,,True
5323d48c2b2aa253087b13694b0e8b0bd0f8ccd7,PMC,Association of time-to-treatment with outcomes of Pneumocystis pneumonia with respiratory failure in HIV-negative patients,http://dx.doi.org/10.1186/s12931-019-1188-6,PMC6761721,31554510,CC BY,"BACKGROUND: The prevalence of pneumocystis pneumonia (PCP) and associated hypoxic respiratory failure is increasing in human immunodeficiency virus (HIV)-negative patients. However, no prior studies have evaluated the effect of early anti-PCP treatment on clinical outcomes in HIV-negative patient with severe PCP. Therefore, this study investigated the association between the time to anti-PCP treatment and the clinical outcomes in HIV-negative patients with PCP who presented with hypoxemic respiratory failure. METHODS: A retrospective observational study was performed involving 51 HIV-negative patients with PCP who presented in respiratory failure and were admitted to the intensive care unit between October 2005 and July 2018. A logistic regression model was used to adjust for potential confounding factors in the association between the time to anti-PCP treatment and in-hospital mortality. RESULTS: All patients were treated with appropriate anti-PCP treatment, primarily involving trimethoprim/sulfamethoxazole. The median time to anti-PCP treatment was 58.0 (28.0–97.8) hours. Thirty-one (60.8%) patients were treated empirically prior to confirmation of the microbiological diagnosis. However, the hospital mortality rates were not associated with increasing quartiles of time until anti-PCP treatment (P = 0.818, test for trend). In addition, hospital mortality of patients received early empiric treatment was not better than those of patients received definitive treatment after microbiologic diagnosis (48.4% vs. 40.0%, P = 0.765). In a multiple logistic regression model, the time to anti-PCP treatment was not associated with increased mortality. However, age (adjusted OR 1.07, 95% CI 1.01–1.14) and failure to initial treatment (adjusted OR 13.03, 95% CI 2.34–72.65) were independently associated with increased mortality. CONCLUSIONS: There was no association between the time to anti-PCP treatment and treatment outcomes in HIV-negative patients with PCP who presented in hypoxemic respiratory failure.",2019 Sep 26,"['Ko, Ryoung-Eun', 'Na, Soo Jin', 'Huh, Kyungmin', 'Suh, Gee Young', 'Jeon, Kyeongman']",Respir Res,,,True
ad7576ff127570ebd90067bd6707f02776b687e5,PMC,Animal modeling in bone research—Should we follow the White Rabbit?,http://dx.doi.org/10.1002/ame2.12083,PMC6762042,31773091,CC BY,"Animal models are live subjects applied to translational research. They provide insights into human diseases and enhance biomedical knowledge. Livestock production has favored the pace of human social development over millennia. Today's society is more aware of animal welfare than past generations. The general public has marked objections to animal research and many species are falling into disuse. The search for an ideal methodology to replace animal use is on, but animal modeling still holds great importance to human health. Bone research, in particular, has unmet requirements that in vitro technologies cannot yet fully address. In that sense, standardizing novel models remains necessary and rabbits are gaining in popularity as potential bone models. Our aim here is to provide a broad overview of animal modeling and its ethical implications, followed by a narrower focus on bone research and the role rabbits are playing in the current scenario.",2019 Sep 26,"['Schafrum Macedo, Aline', 'Cezaretti Feitosa, Caroline', 'Yoiti Kitamura Kawamoto, Fernando', 'Vinicius Tertuliano Marinho, Paulo', 'dos Santos Dal‐Bó, Ísis', 'Fiuza Monteiro, Bianca', 'Prado, Leonardo', 'Bregadioli, Thales', 'Antonio Covino Diamante, Gabriel', 'Ricardo Auada Ferrigno, Cassio']",Animal Model Exp Med,,,True
228650bc0429064d800d4b9c5fb0e00c2533a579,PMC,Lipidome profiles of postnatal day 2 vaginal swabs reflect fat composition of gilt’s postnatal diet,http://dx.doi.org/10.1371/journal.pone.0215186,PMC6762109,31557164,CC BY,"We hypothesized that postnatal development of the vagina is impacted by early nutritional environment. Our objective was to determine if lipid profiles of vaginal swabs were different between postnatal gilts suckled by sow or fed milk replacer the first 48 h after birth, with or without a lard-based fat supplement. Gilts (>1.3 kg) were selected at birth across 8 litters and assigned to one of four treatments: 1) suckled by sow (S, n = 8); 2) suckled by sow plus administration of a fat supplement (SF, n = 5); 3) bottle-fed solely milk replacer (B, n = 8); or 4) bottle-fed solely milk replacer plus administration of a fat supplement (BF, n = 7). At 48 h postnatal, vaginal swabs of gilts were taken with a cytology brush, and lipids were extracted for analysis using multiple reaction monitoring (MRM)-profiling. Lipids extracted from serum collected at 48 h from gilts, milk collected at 24 h from sows, and milk replacer were also analyzed with MRM-profiling. Receiver operating characteristic curve analysis found 18 lipids recovered from vaginal swabs that highly distinguished between S and B gilts [area-under-the-curve (AUC) > 0.9], including phosphatidylethanolamine with 34 carbons and four unsaturations in the fatty acyl residues [PE (34:4)]. Twelve lipids from vaginal swabs highly correlated (r > 0.6; p < 0.01) with nutrition source. Lipids with greater abundance in milk replacer drove association. For example, mean intensity of PE (34:4) was 149-fold higher in milk replacer than colostrum. Consequently, PE (34:4) was found to have 1.6- and 2.12-fold higher levels in serum and vaginal swab samples (p < 0.001), respectively, of B gilts as compared to S gilts. Findings support that vaginal swabs can be used to noninvasively study effects of perinatal nutrition on tissue composition.",2019 Sep 26,"['Harlow, KaLynn', 'Ferreira, Christina R.', 'Sobreira, Tiago J. P.', 'Casey, Theresa', 'Stewart, Kara']",PLoS One,,,True
9f4d4c9adc8c45170f5974f896296466e70bb5ee,PMC,Lipidome profiles of postnatal day 2 vaginal swabs reflect fat composition of gilt’s postnatal diet,http://dx.doi.org/10.1371/journal.pone.0215186,PMC6762109,31557164,CC BY,"We hypothesized that postnatal development of the vagina is impacted by early nutritional environment. Our objective was to determine if lipid profiles of vaginal swabs were different between postnatal gilts suckled by sow or fed milk replacer the first 48 h after birth, with or without a lard-based fat supplement. Gilts (>1.3 kg) were selected at birth across 8 litters and assigned to one of four treatments: 1) suckled by sow (S, n = 8); 2) suckled by sow plus administration of a fat supplement (SF, n = 5); 3) bottle-fed solely milk replacer (B, n = 8); or 4) bottle-fed solely milk replacer plus administration of a fat supplement (BF, n = 7). At 48 h postnatal, vaginal swabs of gilts were taken with a cytology brush, and lipids were extracted for analysis using multiple reaction monitoring (MRM)-profiling. Lipids extracted from serum collected at 48 h from gilts, milk collected at 24 h from sows, and milk replacer were also analyzed with MRM-profiling. Receiver operating characteristic curve analysis found 18 lipids recovered from vaginal swabs that highly distinguished between S and B gilts [area-under-the-curve (AUC) > 0.9], including phosphatidylethanolamine with 34 carbons and four unsaturations in the fatty acyl residues [PE (34:4)]. Twelve lipids from vaginal swabs highly correlated (r > 0.6; p < 0.01) with nutrition source. Lipids with greater abundance in milk replacer drove association. For example, mean intensity of PE (34:4) was 149-fold higher in milk replacer than colostrum. Consequently, PE (34:4) was found to have 1.6- and 2.12-fold higher levels in serum and vaginal swab samples (p < 0.001), respectively, of B gilts as compared to S gilts. Findings support that vaginal swabs can be used to noninvasively study effects of perinatal nutrition on tissue composition.",2019 Sep 26,"['Harlow, KaLynn', 'Ferreira, Christina R.', 'Sobreira, Tiago J. P.', 'Casey, Theresa', 'Stewart, Kara']",PLoS One,,,False
42966e386536e2e45a30988e43e762c81e7ca6dc,PMC,Reservoirs of Porcine Circoviruses: A Mini Review,http://dx.doi.org/10.3389/fvets.2019.00319,PMC6763682,31616677,CC BY,"Porcine circovirus (PCV) is one of the smallest known DNA viruses in mammals. At present, PCVs are divided into three species, PCV1, PCV2, and PCV3. PCV1 and PCV2 were found in the 1970s and the 1990s, respectively, whereas PCV3 was discovered recently in 2016. PCV1 does not cause diseases in pigs. However, PCV3, similar to PCV2, is reported to be associated with several swine diseases, including porcine dermatitis and nephropathy syndrome (PDNS) and reproductive failure. PCVs are very common in domestic pigs as well as wild boars. However, PCVs have been occasionally isolated from non-porcine animals, including ruminants (such as cattle, goats, wild chamois, and roe deers), rodents (such as NMRI mice, BALB/c mice, Black C57 mice, ICR mice, Mus musculus, and Rattus rattus), canines (such as dogs, minks, foxes, and raccoon dogs), insects (such as flies, mosquitoes, and ticks), and shellfish. Moreover, PCVs are frequently reported in biological products, including human vaccines, animal vaccines, porcine-derived commercial pepsin products, and many cell lines. PCVs are also abundant in the environment, including water samples and air samples. Interestingly, PCV1 and/or PCV2 antibody or antigen has also been detected in sera, stool samples and respiratory swab samples of human, revealing zoonotic potential of PCVs. Thus, PCVs inhabit many types of reservoirs. In this review, we summarize the reservoirs of PCVs, and this information would be helpful in understanding the natural circulating status and possible cross-species transmission of PCVs.",2019 Sep 19,"['Zhai, Shao-Lun', 'Lu, Shou-Sheng', 'Wei, Wen-Kang', 'Lv, Dian-Hong', 'Wen, Xiao-Hui', 'Zhai, Qi', 'Chen, Qin-Ling', 'Sun, Yan-Wei', 'Xi, Yun']",Front Vet Sci,,,True
d5bcb5d8c2edd7162e5f0fe6c189662b39eebfbe,PMC,The Role of EGFR in Influenza Pathogenicity: Multiple Network-Based Approaches to Identify a Key Regulator of Non-lethal Infections,http://dx.doi.org/10.3389/fcell.2019.00200,PMC6763731,31616667,CC BY,"Despite high sequence similarity between pandemic and seasonal influenza viruses, there is extreme variation in host pathogenicity from one viral strain to the next. Identifying the underlying mechanisms of variability in pathogenicity is a critical task for understanding influenza virus infection and effective management of highly pathogenic influenza virus disease. We applied a network-based modeling approach to identify critical functions related to influenza virus pathogenicity using large transcriptomic and proteomic datasets from mice infected with six influenza virus strains or mutants. Our analysis revealed two pathogenicity-related gene expression clusters; these results were corroborated by matching proteomics data. We also identified parallel downstream processes that were altered during influenza pathogenesis. We found that network bottlenecks (nodes that bridge different network regions) were highly enriched in pathogenicity-related genes, while network hubs (highly connected network nodes) were significantly depleted in these genes. We confirmed that this trend persisted in a distinct virus: Severe Acute Respiratory Syndrome Coronavirus (SARS). The role of epidermal growth factor receptor (EGFR) in influenza pathogenesis, one of the bottleneck regulators with corroborating signals across transcript and protein expression data, was tested and validated in additional mouse infection experiments. We demonstrate that EGFR is important during influenza infection, but the role it plays changes for lethal versus non-lethal infections. Our results show that by using association networks, bottleneck genes that lack hub characteristics can be used to predict a gene’s involvement in influenza virus pathogenicity. We also demonstrate the utility of employing multiple network approaches for analyzing host response data from viral infections.",2019 Sep 20,"['Mitchell, Hugh D.', 'Eisfeld, Amie J.', 'Stratton, Kelly G.', 'Heller, Natalie C.', 'Bramer, Lisa M.', 'Wen, Ji', 'McDermott, Jason E.', 'Gralinski, Lisa E.', 'Sims, Amy C.', 'Le, Mai Q.', 'Baric, Ralph S.', 'Kawaoka, Yoshihiro', 'Waters, Katrina M.']",Front Cell Dev Biol,,,True
38a24f1500fcb5cfbac618720eb8996fd27029a4,PMC,"Extrapolating Antibiotic Sales to Number of Treated Animals: Treatments in Pigs and Calves in Switzerland, 2011–2015",http://dx.doi.org/10.3389/fvets.2019.00318,PMC6763737,31616676,CC BY,"To evaluate the contribution of antimicrobial use in human and veterinary medicine to the emergence and spread of resistant bacteria, the use of these substances has to be accurately monitored in each setting. Currently, various initiatives collect sales data of veterinary antimicrobials, thereby providing an overview of quantities on the market. However, sales data collected at the level of wholesalers or marketing authorization holders are of limited use to associate with the prevalence of bacterial resistances at species level. We converted sales data to the number of potential treatments of calves and pigs in Switzerland for the years 2011 to 2015 using animal course doses (ACD). For each authorized product, the number of potential therapies was derived from the sales at wholesaler's level and the ACD in mg per kg. For products registered for use in multiple species, a percentage of the sales was attributed to each authorized species according to their biomass distribution. We estimated a total of 5,914,349 therapies for pigs and 1,407,450 for calves in 2015. Using the number of slaughtered animals for that year as denominator, we calculated a treatment intensity of 2.15 therapies per pig and 5.96 per calf. Between 2011 and 2015, sales of veterinary antimicrobials decreased by 30%. The calculated number of potential therapies decreased by 30% for pigs and 15% for calves. An analysis of treatment intensity at antimicrobial class level showed a decrease of 64% for colistin used in pigs, and of 7% for macrolides used in both pigs and calves. Whereas the use of 3rd and 4th generation cephalosporins in calves decreased by 15.8%, usage of fluoroquinolones increased by 10.8% in the same period. Corresponding values for pigs were −16.4 and +0.7%. This is the first extrapolation of antimicrobial usage at product level for pigs and calves in Switzerland. It shows that calves were more frequently treated than pigs with a decreasing trend for both number of therapies and use of colistin, macrolides and cephalosporins 3rd and 4th generations. Nonetheless, we calculated an increase in the usage of fluoroquinolones. Altogether, this study's outcomes allow for trend analysis and can be used to assess the relationship between antimicrobial use and resistance at the national level.",2019 Sep 20,"['Stebler, Rosa', 'Carmo, Luís P.', 'Heim, Dagmar', 'Naegeli, Hanspeter', 'Eichler, Klaus', 'Muentener, Cedric R.']",Front Vet Sci,,,True
f3f9545f7a7fee9a2b6d72c0cd36ca66687809be,PMC,Effects of Xinjiaxiangruyin on the TLR7 pathway in influenza virus-infected lungs of mice housed in a hygrothermal environment,http://dx.doi.org/10.1186/s13020-019-0256-7,PMC6764144,31572491,CC BY,"BACKGROUND: To investigate the effects and immunological mechanisms of the traditional Chinese medicine Xinjiaxiangruyin on controlling influenza virus (FM1 strain) infection in mice housed in a hygrothermal environment. METHODS: Mice were housed in normal and hygrothermal environments, and intranasally infected with influenza virus (FM1). A high-performance liquid chromatography fingerprint of Xinjiaxiangruyin was used to provide an analytical method for quality control. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure messenger RNA expression of Toll-like receptor 7 (TLR7), myeloid differentiation primary response 88 (MyD88), and nuclear factor-kappa B (NF-κB) p65 in the TLR7 signaling pathway and virus replication in the lungs. Western blotting was used to measure the expression levels of TLR7, MyD88, and NF-κB p65 proteins. Flow cytometry was used to detect the proportion of Th17/T-regulatory cells. RESULTS: Xinjiaxiangruyin effectively alleviated lung inflammation in C57BL/6 mice in hot and humid environments. Guizhimahuanggebantang significantly reduced lung inflammation in C57BL/6 mice. The expression of TLR7, MyD88, and NF-κB p65 mRNA in lung tissue of WT mice in the normal environment, GZMHGBT group was significantly lower than that in the model group (P < 0.05). In WT mice exposed to the hot and humid environment, the expression levels of TLR7, MyD88, and NF-κB p65 mRNA in the XJXRY group were significantly different from those in the virus group. The expression levels of TLR7, MyD88, and NF-κB p65 protein in lung tissue of WT mice exposed to the normal environment, GZMHGBT group was significantly lower than those in the model group. In WT mice exposed to hot and humid environments, the expression levels of TLR7, MyD88, and NF-κB p65 protein in XJXRY group were significantly different from those in the virus group. CONCLUSION: Guizhimahuanggebantang demonstrated a satisfactory therapeutic effect on mice infected with the influenza A virus (FM1 strain) in a normal environment, and Xinjiaxiangruyin demonstrated a clear therapeutic effect in damp and hot environments and may play a protective role against influenza through downregulation of the TLR7 signal pathway.",2019 Sep 27,"['Fu, Ying-Jie', 'Yan, Yu-Qi', 'Zheng, Xiao', 'Shi, Shan-Shan', 'Wu, Sha', 'Jiang, Zhen-You']",Chin Med,,,True
6cbe44ed557bcc33f3373f4901da645d23e37901,PMC,Evaluation of Public Health Emergency Management in China: A Systematic Review,http://dx.doi.org/10.3390/ijerph16183478,PMC6766041,31540510,CC BY,"To summarize the present status of health emergency management assessment in China, a comprehensive search of Chinese databases for research that explicitly mention health emergency assessment indicators and indicator systems was performed. Studies were evaluated using the Ekman quality assessment tool, and data were extracted with an original extraction form. Sixty-one studies were included. There are many types and methods of health emergency management assessment in China, and the dimensions and the indicators involved are complex. Legal, regulatory, and policy bases for such assessment need to be further strengthened. The relevance of the entire assessment process and its practical application should be enhanced. In the occupational practice, appropriate evaluation methods should be selected according to respective evaluation purposes, evaluation objects, and contents. Laws, regulations, and policies in the evaluation of health emergency management should be improved. Finally, further correlational research on health emergency management evaluation system processes should be explored and improved.",2019 Sep 18,"['Wang, Jia', 'Yuan, Beibei', 'Li, Zhengmao', 'Wang, Zhifeng']",Int J Environ Res Public Health,,,True
d0631859c5008f863d1b288755b97bb0b6dea4d6,PMC,Development of a Single Leg Knee Exoskeleton and Sensing Knee Center of Rotation Change for Intention Detection,http://dx.doi.org/10.3390/s19183960,PMC6767670,31540298,CC BY,"In this study, we developed a single leg knee joint assistance robot. Commonly used exoskeletons have a left-right pair, but when only one leg of the wearer is uncomfortable, it is effective to wear the exoskeleton on only the uncomfortable leg. The designed exoskeleton uses a lightweight material and uses a wire-driven actuator, which reduces the weight of the driving section that is attached on the knee directly. Therefore, proposed exoskeleton reduces the force of inertia that the wearer experiences. In addition, the lower frame length of the exoskeleton can be changed to align with the complex movement of the knee. Furthermore, the length between the knee center of rotation and the ankle (LBKA) is measured by using this structure, and the LBKA values are used as the data for intention detection. These value helps to detect the intention because it changes faster than a motor encoder value. A neural network was trained using the motor encoder values, and LBKA values. Neural network detects the intention of three motions (stair ascending, stair descending, and walking), Training results showed that intention detection was good in various environments.",2019 Sep 13,"['Moon, Dae-Hoon', 'Kim, Donghan', 'Hong, Young-Dae']",Sensors (Basel),,,True
ff2a6501716b8ff2b5e96ef3034f15309ce90c43,PMC,Hepatitis C virus modelled as an indirectly transmitted infection highlights the centrality of injection drug equipment in disease dynamics,http://dx.doi.org/10.1098/rsif.2019.0334,PMC6769301,31480919,CC BY,"The hepatitis C virus (HCV) epidemic often occurs through the persistence of injection drug use. Mathematical models have been useful in understanding various aspects of the HCV epidemic, and especially, the importance of new treatment measures. Until now, however, few models have attempted to understand HCV in terms of an interaction between the various actors in an HCV outbreak—hosts, viruses and the needle injection equipment. In this study, we apply perspectives from the ecology of infectious diseases to model the transmission of HCV among a population of injection drug users. The products of our model suggest that modelling HCV as an indirectly transmitted infection—where the injection equipment serves as an environmental reservoir for infection—facilitates a more nuanced understanding of disease dynamics, by animating the underappreciated actors and interactions that frame disease. This lens may allow us to understand how certain public health interventions (e.g. needle exchange programmes) influence HCV epidemics. Lastly, we argue that this model is of particular importance in the light of the modern opioid epidemic, which has already been associated with outbreaks of viral diseases.",2019 Sep 4,"['Miller-Dickson, Miles D.', 'Meszaros, Victor A.', 'Almagro-Moreno, Salvador', 'Brandon Ogbunugafor, C.']",J R Soc Interface,,,True
63d069bab41ecd46a0c6462f46f27844322cad61,PMC,Hepatitis C virus modelled as an indirectly transmitted infection highlights the centrality of injection drug equipment in disease dynamics,http://dx.doi.org/10.1098/rsif.2019.0334,PMC6769301,31480919,CC BY,"The hepatitis C virus (HCV) epidemic often occurs through the persistence of injection drug use. Mathematical models have been useful in understanding various aspects of the HCV epidemic, and especially, the importance of new treatment measures. Until now, however, few models have attempted to understand HCV in terms of an interaction between the various actors in an HCV outbreak—hosts, viruses and the needle injection equipment. In this study, we apply perspectives from the ecology of infectious diseases to model the transmission of HCV among a population of injection drug users. The products of our model suggest that modelling HCV as an indirectly transmitted infection—where the injection equipment serves as an environmental reservoir for infection—facilitates a more nuanced understanding of disease dynamics, by animating the underappreciated actors and interactions that frame disease. This lens may allow us to understand how certain public health interventions (e.g. needle exchange programmes) influence HCV epidemics. Lastly, we argue that this model is of particular importance in the light of the modern opioid epidemic, which has already been associated with outbreaks of viral diseases.",2019 Sep 4,"['Miller-Dickson, Miles D.', 'Meszaros, Victor A.', 'Almagro-Moreno, Salvador', 'Brandon Ogbunugafor, C.']",J R Soc Interface,,,True
f46dfc953ba5eba42f02a55f53fdafab33736135,PMC,How to Avoid a No-Deal ER Exit,http://dx.doi.org/10.3390/cells8091051,PMC6769657,31500301,CC BY,"Efficiency and fidelity of protein secretion are achieved thanks to the presence of different steps, located sequentially in time and space along the secretory compartment, controlling protein folding and maturation. After entering into the endoplasmic reticulum (ER), secretory proteins attain their native structure thanks to specific chaperones and enzymes. Only correctly folded molecules are allowed by quality control (QC) mechanisms to leave the ER and proceed to downstream compartments. Proteins that cannot fold properly are instead retained in the ER to be finally destined to proteasomal degradation. Exiting from the ER requires, in most cases, the use of coated vesicles, departing at the ER exit sites, which will fuse with the Golgi compartment, thus releasing their cargoes. Protein accumulation in the ER can be caused by a too stringent QC or by ineffective transport: these situations could be deleterious for the organism, due to the loss of the secreted protein, and to the cell itself, because of abnormal increase of protein concentration in the ER. In both cases, diseases can arise. In this review, we will describe the pathophysiology of protein folding and transport between the ER and the Golgi compartment.",2019 Sep 7,"['Anelli, Tiziana', 'Panina-Bordignon, Paola']",Cells,,,True
1e981bc1ac8d6a8ea0f8e21991e3f525ae0a16a4,PMC,RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications,http://dx.doi.org/10.3390/cells8090986,PMC6770044,31461941,CC BY,"The human nasal epithelium is the primary site of exposure to influenza virus, the initiator of host responses to influenza and the resultant pathologies. Influenza virus may cause serious respiratory infection resulting in major complications, as well as severe impairment of the airways. Here, we elucidated the global transcriptomic changes during H3N2 infection of human nasal epithelial cells from multiple individuals. Using RNA sequencing, we characterized the differentially-expressed genes and pathways associated with changes occurring at the nasal epithelium following infection. We used in vitro differentiated human nasal epithelial cell culture model derived from seven different donors who had no concurrent history of viral infections. Statistical analysis highlighted strong transcriptomic signatures significantly associated with 24 and 48 h after infection, but not at the earlier 8-h time point. In particular, we found that the influenza infection induced in the nasal epithelium early and altered responses in interferon gamma signaling, B-cell signaling, apoptosis, necrosis, smooth muscle proliferation, and metabolic alterations. These molecular events initiated at the infected nasal epithelium may potentially adversely impact the airway, and thus the genes we identified could serve as potential diagnostic biomarkers or therapeutic targets for influenza infection and associated disease management.",2019 Aug 27,"['Tan, Kai Sen', 'Andiappan, Anand Kumar', 'Lee, Bernett', 'Yan, Yan', 'Liu, Jing', 'Tang, See Aik', 'Lum, Josephine', 'He, Ting Ting', 'Ong, Yew Kwang', 'Thong, Mark', 'Lim, Hui Fang', 'Choi, Hyung Won', 'Rotzschke, Olaf', 'Chow, Vincent T', 'Wang, De Yun']",Cells,,,True
3e8d0363f49f83917e0ddddf7b4322186da47dbc,PMC,Viral Metagenomics in the Clinical Realm: Lessons Learned from a Swiss-Wide Ring Trial,http://dx.doi.org/10.3390/genes10090655,PMC6770386,31466373,CC BY,"Shotgun metagenomics using next generation sequencing (NGS) is a promising technique to analyze both DNA and RNA microbial material from patient samples. Mostly used in a research setting, it is now increasingly being used in the clinical realm as well, notably to support diagnosis of viral infections, thereby calling for quality control and the implementation of ring trials (RT) to benchmark pipelines and ensure comparable results. The Swiss NGS clinical virology community therefore decided to conduct a RT in 2018, in order to benchmark current metagenomic workflows used at Swiss clinical virology laboratories, and thereby contribute to the definition of common best practices. The RT consisted of two parts (increments), in order to disentangle the variability arising from the experimental compared to the bioinformatics parts of the laboratory pipeline. In addition, the RT was also designed to assess the impact of databases compared to bioinformatics algorithms on the final results, by asking participants to perform the bioinformatics analysis with a common database, in addition to using their own in-house database. Five laboratories participated in the RT (seven pipelines were tested). We observed that the algorithms had a stronger impact on the overall performance than the choice of the reference database. Our results also suggest that differences in sample preparation can lead to significant differences in the performance, and that laboratories should aim for at least 5–10 Mio reads per sample and use depth of coverage in addition to other interpretation metrics such as the percent of coverage. Performance was generally lower when increasing the number of viruses per sample. The lessons learned from this pilot study will be useful for the development of larger-scale RTs to serve as regular quality control tests for laboratories performing NGS analyses of viruses in a clinical setting.",2019 Aug 28,"['Junier, Thomas', 'Huber, Michael', 'Schmutz, Stefan', 'Kufner, Verena', 'Zagordi, Osvaldo', 'Neuenschwander, Stefan', 'Ramette, Alban', 'Kubacki, Jakub', 'Bachofen, Claudia', 'Qi, Weihong', 'Laubscher, Florian', 'Cordey, Samuel', 'Kaiser, Laurent', 'Beuret, Christian', 'Barbié, Valérie', 'Fellay, Jacques', 'Lebrand, Aitana']",Genes (Basel),,,True
01880ef487dfed3681dd6d296a0a82417b8f38a0,PMC,Impact of RNA Virus Evolution on Quasispecies Formation and Virulence,http://dx.doi.org/10.3390/ijms20184657,PMC6770471,31546962,CC BY,"RNA viruses are known to replicate by low fidelity polymerases and have high mutation rates whereby the resulting virus population tends to exist as a distribution of mutants. In this review, we aim to explore how genetic events such as spontaneous mutations could alter the genomic organization of RNA viruses in such a way that they impact virus replications and plaque morphology. The phenomenon of quasispecies within a viral population is also discussed to reflect virulence and its implications for RNA viruses. An understanding of how such events occur will provide further evidence about whether there are molecular determinants for plaque morphology of RNA viruses or whether different plaque phenotypes arise due to the presence of quasispecies within a population. Ultimately this review gives an insight into whether the intrinsically high error rates due to the low fidelity of RNA polymerases is responsible for the variation in plaque morphology and diversity in virulence. This can be a useful tool in characterizing mechanisms that facilitate virus adaptation and evolution.",2019 Sep 19,"['Mandary, Madiiha Bibi', 'Masomian, Malihe', 'Poh, Chit Laa']",Int J Mol Sci,,,True
1358b278b691bdd7439d849fa8a002f9f9b8fe95,PMC,Molecular and Antigenic Characterization of GI-13 and GI-16 Avian Infectious Bronchitis Virus Isolated in Chile from 2009 to 2017 Regarding 4/91 Vaccine Introduction,http://dx.doi.org/10.3390/ani9090656,PMC6770500,31491868,CC BY,"SIMPLE SUMMARY: The high adaptation and recombination abilities of infectious bronchitis virus (IB) have been proven. This study aims to verify the genetic and antigenic variation of eight field IB strains regarding the 4/91 strain vaccination in Chilean chickens. Phylogenetic, serologic and challenge studies were carried out to accomplish this goal. The genetic analyses indicate that all the viruses isolated prior to the 4/91 introduction belong to the genetic group GI-16 (three isolates from 2009). On the other hand, just one of the viruses isolated after the 4/91 strain vaccine introduction in Chile (in 2015) showed relationship with GI-16 lineage. The remaining four viruses (from 2017) belong to GI-13, the group where the strain 4/91 has been previously classified. Three viruses were chosen to perform antigenic and protective studies. Antigenically, the high relationship between the 4/91 vaccine with the isolate from 2017 is remarkable and could not be observed with isolates from 2009 and 2015. The 4/91 vaccine also showed better protection against the isolate from 2017 than isolates from 2009 and 2015. These results suggest that the introduction of the 4/91 vaccine in Chile could imply a change in some viruses, showing its ability to interact with field viruses, so it is important to monitor the circulating viruses and include these results in future governmental decisions. ABSTRACT: The introduction of the 4/91 vaccine against infectious bronchitis in Chile, a lineage not described until that time in the country, led to looking for changes induced by this action. This study considers eight isolates obtained from 2009, 2015 and 2017 and uses a maximum likelihood approach to classify the field isolates. Three isolates were selected to analyze antigenic relationships through a virus neutralization test and to perform protection tests measured trough an RT-qPCR. The isolates from 2009 and 2015 showed a relationship with GI-16 while those from 2017 were related to GI-13. Though the field isolates were classified in two different phylogenetic lineages, all of them showed only minor variations in subtype. The 13885R-17 isolate from 2017 exhibited high antigenic relatedness to the 4/91 vaccine. As expected, 4/91 and Massachusetts vaccines were not antigenically related. Vaccinated birds with the 4/91 vaccine showed less tracheal virus replication for the 13885R-17 from 2017 challenge than for the 12101SP-09 from 2009 and 13347SP-15 from 2015 isolates. The results indicated genetic and antigenic diversity in the most recent infectious bronchitis virus (IBV) isolates in Chile. Moreover, the 4/91 vaccine would be involved in the generation of some current field viruses, which must be considered in vaccination programs and public policies.",2019 Sep 5,"['Guzmán, Miguel', 'Sáenz, Leonardo', 'Hidalgo, Héctor']",Animals (Basel),,,True
0435b8c5081db34e2c6c62b8f7b998927fa28776,PMC,"The Redox Role of G6PD in Cell Growth, Cell Death, and Cancer",http://dx.doi.org/10.3390/cells8091055,PMC6770671,31500396,CC BY,"The generation of reducing equivalent NADPH via glucose-6-phosphate dehydrogenase (G6PD) is critical for the maintenance of redox homeostasis and reductive biosynthesis in cells. NADPH also plays key roles in cellular processes mediated by redox signaling. Insufficient G6PD activity predisposes cells to growth retardation and demise. Severely lacking G6PD impairs embryonic development and delays organismal growth. Altered G6PD activity is associated with pathophysiology, such as autophagy, insulin resistance, infection, inflammation, as well as diabetes and hypertension. Aberrant activation of G6PD leads to enhanced cell proliferation and adaptation in many types of cancers. The present review aims to update the existing knowledge concerning G6PD and emphasizes how G6PD modulates redox signaling and affects cell survival and demise, particularly in diseases such as cancer. Exploiting G6PD as a potential drug target against cancer is also discussed.",2019 Sep 8,"['Yang, Hung-Chi', 'Wu, Yi-Hsuan', 'Yen, Wei-Chen', 'Liu, Hui-Ya', 'Hwang, Tsong-Long', 'Stern, Arnold', 'Chiu, Daniel Tsun-Yee']",Cells,,,True
82ebbe8f7da98684d3f627254627253f080e09b5,PMC,Allele-Specific Expression of CD4(+) T Cells in Response to Marek’s Disease Virus Infection,http://dx.doi.org/10.3390/genes10090718,PMC6770979,31533276,CC BY,"Marek’s disease (MD) is a T cell lymphoma disease induced by Marek’s disease virus (MDV), a highly oncogenic α herpesvirus primarily affecting chickens. MD is a chronic infectious disease that threatens the poultry industry. However, the mechanisms of genetic resistance for MD are complex and not completely understood. In this study, to identify high-confidence candidate genes of MD genetic resistance, high throughput sequencing (RNA-seq) was used to obtain transcriptomic data of CD4(+) T cells isolated from MDV-infected and non-infected groups of two reciprocal crosses of individuals mating by two highly inbred chicken lines (6(3) MD-resistant and 7(2) MD-susceptible). After RNA-seq analysis with two biological replicates in each group, we identified 61 and 123 single nucleotide polymorphisms (SNPs) (false discovery rate (FDR) < 0.05) annotated in 39 and 132 genes in intercrosses 6(3) × 7(2) and 7(2) × 6(3), respectively, which exhibited allele-specific expression (ASE) in response to MDV infection. Similarly, we identified 62 and 79 SNPs annotated in 66 and 96 genes in infected and non-infected groups, respectively. We identified 534 and 1543 differentially expressed genes (DEGs) (FDR < 0.05) related to MDV infection in intercrosses 6(3) × 7(2) and 7(2) × 6(3), respectively. We also identified 328 and 20 DEGs in infected and non-infected groups, respectively. The qRT-PCR using seven DEGs further verified our results of RNA-seq analysis. The qRT-PCR of 11 important ASE genes was performed for gene functional validation in CD4(+) T cells and tumors. Combining the analyses, six genes (MCL1, SLC43A2, PDE3B, ADAM33, BLB1, and DMB2), especially MCL1, were highlighted as the candidate genes with the potential to be involved in MDV infection. Gene-set enrichment analysis revealed that many ASE genes are linked to T cell activation, T cell receptor (TCR), B cell receptor (BCR), ERK/MAPK, and PI3K/AKT-mTOR signaling pathways, which play potentially important roles in MDV infection. Our approach underlines the importance of comprehensive functional studies for gaining valuable biological insight into the genetic factors behind MD and other complex traits, and our findings provide additional insights into the mechanisms of MD and disease resistance breeding in poultry.",2019 Sep 17,"['Bai, Hao', 'He, Yanghua', 'Ding, Yi', 'Carrillo, José A.', 'Selvaraj, Ramesh K.', 'Zhang, Huanmin', 'Chen, Jilan', 'Song, Jiuzhou']",Genes (Basel),,,True
25d0bd17e76d262df4c2948ef2d8a5270f00871a,PMC,Transcriptome analysis of PK-15 cells in innate immune response to porcine deltacoronavirus infection,http://dx.doi.org/10.1371/journal.pone.0223177,PMC6773216,31574122,CC BY,"Porcine deltacoronavirus (PDCoV) is a newly emerged swine enteropathogenic coronavirus affecting pigs of all ages and causing diarrhea problems. Research findings indicate that PDCoV has evolved strategies to escape innate immune response in host cells, but mechanism of PDCoV in innate immune modulation is not well understood. In this study, we report our findings on identifying the alterations of host cell innate immune response affected by PDCoV infection and exploring the gene expression profiles of PK-15 cells at 0, 24, and 36 h PDCoV post infection by RNA sequencing. A total of 3,762 and 560 differentially expressed genes (DEGs) were screened by comparison of uninfected PK-15 cells and infected PK-15 cells at 24 h post infection (hpi) (INF_24h versus NC), and also comparison of infected PK-15 cells between 24 and 36 hpi (INF_36h versus INF_24h), which included 156 and 23 porcine innate immune-related genes in the DEGs of INF_24h versus NC and INF_36h versus INF_24h, respectively. Gene Ontology function classification and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analysis were performed based on the DEGs that exhibited the same expression tendencies with most of the innate immune-associated genes among these PK-15 cell samples described above. The enrichment results indicated that extensive gene functions and signaling pathways including innate immune-associated functions and pathways were affected by PDCoV infection. Particularly, 4 of 5 innate immune signaling pathways, which were primarily affected by PDCoV, played important roles in I-IFN’s antiviral function in innate immune response. Additionally, 16 of the host cell endogenous miRNAs were predicted as potential contributors to the modulation of innate immune response affected by PDCoV. Our research findings indicated that the innate immune-associated genes and signaling pathways in PK-15 cells could be modified by the infection of PDCoV, which provides a fundamental foundation for further studies to better understand the mechanism of PDCoV infections, so as to effectively control and prevent PDCoV-induced swine diarrheal disease outbreaks.",2019 Oct 1,"['Jiang, Shan', 'Li, Fuqiang', 'Li, Xiuli', 'Wang, Lili', 'Zhang, Li', 'Lu, Chao', 'Zheng, Li', 'Yan, Minghua']",PLoS One,,,True
11bf75e973011d86b1039b707ed086b98deb5642,PMC,Human Monoclonal Antibodies as Adjuvant Treatment of Chronic Hepatitis B Virus Infection,http://dx.doi.org/10.3389/fimmu.2019.02290,PMC6773823,31608071,CC BY,"Despite the availability of an effective prophylactic vaccine leading to sterilizing immunity, hepatitis B virus (HBV) is responsible for chronic liver disease in more than 250 million individuals, potentially leading to cirrhosis and hepatocellular carcinoma. Antiviral drugs able to completely suppress virus replication are indeed available but they are, by and large, unable to eradicate the virus. Several alternative new treatment approaches are currently being developed but none have so far captured the interest of clinicians for possible clinical development. A constant feature of chronic HBV infection is T-cell exhaustion resulting from persistent exposure to high antigen concentrations as shown by the high expression of programmed cell death protein 1 (PD-1) by HBV-specific CD8 T cells. One way of tackling this problem is to develop HBV-specific neutralizing antibodies that would clear excess envelope proteins from the circulation, allowing for nucleos(t)ide analogs or other antiviral drugs now in preclinical and early clinical development to take advantage of a reconstituted adaptive immunity. Several fully human monoclonal antibodies (mAb) have been developed from HBV-vaccinated and subjects convalescent from acute hepatitis B that show different properties and specificities. It is envisaged that such neutralizing mAb may be used as adjuvant treatment to reduce viral protein load, thus rescuing adaptive immunity in an effort to optimize the effect of antiviral drugs.",2019 Sep 25,"['Cerino, Antonella', 'Mantovani, Stefania', 'Mele, Dalila', 'Oliviero, Barbara', 'Varchetta, Stefania', 'Mondelli, Mario U.']",Front Immunol,,,True
c4f28354c6015236a080fc0d67b0fc9d193c70d6,PMC,Circular RNA CircEZH2 Suppresses Transmissible Gastroenteritis Coronavirus-induced Opening of Mitochondrial Permeability Transition Pore via Targeting MiR-22 in IPEC-J2,http://dx.doi.org/10.7150/ijbs.36532,PMC6775298,31592229,CC BY,"Transmissible gastroenteritis (TGE) is a contagious and infectious disease that is characterized by severe vomiting and diarrhea of swine , especially piglet, and caused by transmissible gastroenteritis coronavirus (TGEV) . TGEV infection provokes mitochondrial damage of porcine intestinal epthelial cell (IPEC), which is responsible for inflammation and cell death. In our previous study, we have demonstrated that circular RNA circEZH2 was down-regulated during TGEV infection and promoted the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) via targeting miR-22 in porcine intestinal epithelial cell line (IPEC-J2). Activation of NF-κB is an important factor for mitochondrial damage. Mitochondrial permeability transition pore (mPTP) opening is a key reason for mitochondrial damage. So, we speculate that circEZH2 may regulate TGEV-induced mPTP opening via NF-kB pathway. In the present study, we found that mPTP opening of IPEC-J2 was occured during TGEV infection and suppressed by circEZH2 via attaching miR-22. Hexokinase 2 (HK2) and interleukin 6 (IL-6) were identified as the targets of miR-22. Silencing HK2 enhanced TGEV-induced mPTP opening, while no effect on NF-κB pathway. Silencing IL-6 promoted TGEV-induced mPTP opening and inhibited NF-κB pathway. Inhibitor of NF-κB increased TGEV-induced mPTP opening. The data revealed that TGEV-induced mPTP opening was regulated via two pathways: circEZH2/miR-22/HK2 axis and circEZH2/miR-22/IL-6/NF-κB axis.",2019 Jul 25,"['Zhao, Xiaomin', 'Ma, Xuelian', 'Guo, Jianxiong', 'Mi, Mi', 'Wang, Kaili', 'Zhang, Chuyi', 'Tang, Xiaoyi', 'Chang, Lingling', 'Huang, Yong', 'Tong, Dewen']",Int J Biol Sci,,,True
d59fa3076206ec958f96dfe7456da8b10c6b93df,PMC,Circular RNA CircEZH2 Suppresses Transmissible Gastroenteritis Coronavirus-induced Opening of Mitochondrial Permeability Transition Pore via Targeting MiR-22 in IPEC-J2,http://dx.doi.org/10.7150/ijbs.36532,PMC6775298,31592229,CC BY,"Transmissible gastroenteritis (TGE) is a contagious and infectious disease that is characterized by severe vomiting and diarrhea of swine , especially piglet, and caused by transmissible gastroenteritis coronavirus (TGEV) . TGEV infection provokes mitochondrial damage of porcine intestinal epthelial cell (IPEC), which is responsible for inflammation and cell death. In our previous study, we have demonstrated that circular RNA circEZH2 was down-regulated during TGEV infection and promoted the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) via targeting miR-22 in porcine intestinal epithelial cell line (IPEC-J2). Activation of NF-κB is an important factor for mitochondrial damage. Mitochondrial permeability transition pore (mPTP) opening is a key reason for mitochondrial damage. So, we speculate that circEZH2 may regulate TGEV-induced mPTP opening via NF-kB pathway. In the present study, we found that mPTP opening of IPEC-J2 was occured during TGEV infection and suppressed by circEZH2 via attaching miR-22. Hexokinase 2 (HK2) and interleukin 6 (IL-6) were identified as the targets of miR-22. Silencing HK2 enhanced TGEV-induced mPTP opening, while no effect on NF-κB pathway. Silencing IL-6 promoted TGEV-induced mPTP opening and inhibited NF-κB pathway. Inhibitor of NF-κB increased TGEV-induced mPTP opening. The data revealed that TGEV-induced mPTP opening was regulated via two pathways: circEZH2/miR-22/HK2 axis and circEZH2/miR-22/IL-6/NF-κB axis.",2019 Jul 25,"['Zhao, Xiaomin', 'Ma, Xuelian', 'Guo, Jianxiong', 'Mi, Mi', 'Wang, Kaili', 'Zhang, Chuyi', 'Tang, Xiaoyi', 'Chang, Lingling', 'Huang, Yong', 'Tong, Dewen']",Int J Biol Sci,,,False
0712e5735c51991b7e0ce4bd5e63882703863459,PMC,"On the Emergence of Cryptococcus gattii in the Pacific Northwest: Ballast Tanks, Tsunamis, and Black Swans",http://dx.doi.org/10.1128/mBio.02193-19,PMC6775458,31575770,CC BY,"The appearance of Cryptococcus gattii in the North American Pacific Northwest (PNW) in 1999 was an unexpected and is still an unexplained event. Recent phylogenomic analyses strongly suggest that this pathogenic fungus arrived in the PNW approximately 7 to 9 decades ago. In this paper, we theorize that the ancestors of the PNW C. gattii clones arrived in the area by shipborne transport, possibly in contaminated ballast, and established themselves in coastal waters early in the 20th century. In 1964, a tsunami flooded local coastal regions, transporting C. gattii to land. The occurrence of cryptococcosis in animals and humans 3 decades later suggests that adaptation to local environs took time, possibly requiring an increase in virulence and further dispersal. Tsunamis as a mechanism for the seeding of land with pathogenic waterborne microbes may have important implications for our understanding of how infectious diseases emerge in certain regions. This hypothesis suggests experimental work for its validation or refutation.",2019 Oct 1,"['Engelthaler, David M.', 'Casadevall, Arturo']",mBio,,,True
fccc2cff358d6c08f512003b88bab9934e4ffa7a,PMC,The Underlying Mechanism of 3-Hydroxyphthalic Anhydride-Modified Bovine Beta-Lactoglobulin to Block Human Papillomavirus Entry Into the Host Cell,http://dx.doi.org/10.3389/fmicb.2019.02188,PMC6775479,31611852,CC BY,"We have previously demonstrated that 3-hydroxyphthalic anhydride (3HP)-modified bovine beta-lactoglobulin (3HP-β-LG) is highly effective in inhibiting entry of pseudovirus (PsV) of high- and low-risk human papillomavirus (HPV) into the target cell. Intravaginally applied 3HP-β-LG-containing vaginal gel could significantly inhibit HPV infection and reduce viral load in the cervical region. However, we still do not understand the underlying molecular mechanism by which 3HP-β-LG is able to inhibit HPV infection. Here, though, we showed that 3HP-β-LG did not inactivate HPV PsV, but rather blocked entry of HPV PsV into the target cell via its interaction with virus, not cell. It bound to the positively charged region in the HPV L1 protein, suggesting that 3HP-β-LG binds to HPV L1 protein through the interaction between the negatively charged region in 3HP-β-LG and the positively charged region in HPV L1 protein, thus competitively blocking the binding of HPV to the receptor on the basement membrane in vaginal mucosa. Although 3HP-modified chicken ovalbumin (3HP-OVA) also carries high net negative charges, it exhibited no anti-HPV activity, suggesting that the interaction between 3HP-modified protein and HPV L1 protein relies on both electrostatic and matchable conformation of the binding sites in both proteins. When topically applied, 3HP-β-LG did not enter the host cell or blood circulation. These findings suggest that 3HP-β-LG targets HPV L1 protein and blocks HPV entry into the host cell, thus being safe and effective for topical application in the treatment of HPV infection.",2019 Sep 26,"['Hua, Chen', 'Zhu, Yun', 'Wu, Congquan', 'Si, Lulu', 'Wang, Qian', 'Sui, Long', 'Jiang, Shibo']",Front Microbiol,,,True
13580111f45eb6e4af4142774eb95f0e52350e92,PMC,Virome heterogeneity and connectivity in waterfowl and shorebird communities,http://dx.doi.org/10.1038/s41396-019-0458-0,PMC6775988,31239538,CC BY,"Models of host-microbe dynamics typically assume a single-host population infected by a single pathogen. In reality, many hosts form multi-species aggregations and may be infected with an assemblage of pathogens. We used a meta-transcriptomic approach to characterize the viromes of nine avian species in the Anseriformes (ducks) and Charadriiformes (shorebirds). This revealed the presence of 27 viral species, of which 24 were novel, including double-stranded RNA viruses (Picobirnaviridae and Reoviridae), single-stranded RNA viruses (Astroviridae, Caliciviridae, Picornaviridae), a retro-transcribing DNA virus (Hepadnaviridae), and a single-stranded DNA virus (Parvoviridae). These viruses comprise multi-host generalist viruses and those that are host-specific, indicative of both virome connectivity (host sharing) and heterogeneity (host specificity). Virome connectivity was apparent in two well described multi-host virus species -avian coronavirus and influenza A virus- and a novel Rotavirus species that were shared among some Anseriform species, while virome heterogeneity was reflected in the absence of viruses shared between Anseriformes and Charadriiformes, as well as differences in viral abundance and alpha diversity among species. Overall, we demonstrate complex virome structures across host species that co-exist in multi-species aggregations.",2019 Oct 25,"['Wille, Michelle', 'Shi, Mang', 'Klaassen, Marcel', 'Hurt, Aeron C.', 'Holmes, Edward C.']",ISME J,,,True
e8108cdb4654206b4d0e053ce95255aaf71f3303,PMC,Virome heterogeneity and connectivity in waterfowl and shorebird communities,http://dx.doi.org/10.1038/s41396-019-0458-0,PMC6775988,31239538,CC BY,"Models of host-microbe dynamics typically assume a single-host population infected by a single pathogen. In reality, many hosts form multi-species aggregations and may be infected with an assemblage of pathogens. We used a meta-transcriptomic approach to characterize the viromes of nine avian species in the Anseriformes (ducks) and Charadriiformes (shorebirds). This revealed the presence of 27 viral species, of which 24 were novel, including double-stranded RNA viruses (Picobirnaviridae and Reoviridae), single-stranded RNA viruses (Astroviridae, Caliciviridae, Picornaviridae), a retro-transcribing DNA virus (Hepadnaviridae), and a single-stranded DNA virus (Parvoviridae). These viruses comprise multi-host generalist viruses and those that are host-specific, indicative of both virome connectivity (host sharing) and heterogeneity (host specificity). Virome connectivity was apparent in two well described multi-host virus species -avian coronavirus and influenza A virus- and a novel Rotavirus species that were shared among some Anseriform species, while virome heterogeneity was reflected in the absence of viruses shared between Anseriformes and Charadriiformes, as well as differences in viral abundance and alpha diversity among species. Overall, we demonstrate complex virome structures across host species that co-exist in multi-species aggregations.",2019 Oct 25,"['Wille, Michelle', 'Shi, Mang', 'Klaassen, Marcel', 'Hurt, Aeron C.', 'Holmes, Edward C.']",ISME J,,,True
8ad351ba522675d0ec4fa73713649bcfa9453447,PMC,Improved survival rates in patients with H1N1 acute respiratory failure in Korea between 2009 and 2016,http://dx.doi.org/10.1371/journal.pone.0223323,PMC6776345,31581263,CC BY,"There was a pandemic of influenza A (H1N1) in 2009; in Korea, there was also an H1N1 epidemic in 2016. We aim to investigate whether survival had improved in the setting of recent advances in intensive care unit (ICU) management. We conducted a retrospective analysis of acute respiratory failure patients with H1N1 influenza pneumonia in 2016 and 2009 respectively at two tertiary referral hospitals in Korea. A total of 28 patients were treated in 2016, and 34 in 2009. There was no significant difference in SOFA scores on ICU admission day. In-hospital mortality was significantly lower in patients of 2016 compared to those of 2009 (18% vs. 44% P = 0.028). By multivariable analyses, the treatment year 2016 was associated with a greater likelihood of survival. Compared to the patients treated in 2009, those treated in 2016 were one seventh as likely to die after adjusting for other clinical variables (hazard ratio for mortality, 0.15; 95% confidence interval. 0.03–0.63, P = 0.010). Improved survival in patients who underwent extracorporeal membrane oxygenation treatment (in-hospital mortality, 17% vs. 60%, P = 0.242) and decreased tidal volumes during mechanical ventilation (median 5.4 mL/kg vs. median 9.2 mL/kg, P = 0.018) were observed in 2016 compared to 2009. Treatment outcomes for patients with H1N1 acute respiratory failure improved from 2009 to 2016 in two tertiary referral centers in South Korea.",2019 Oct 3,"['Choi, Hayoung', 'Ko, Ui Won', 'Lee, Hyun', 'Hong, Sang-Bum', 'Chung, Chi Ryang']",PLoS One,,,True
81bc2f3c1d93804b0abc16686fe66673dda487f7,PMC,Evolutionary Analysis of the VP1 and RNA-Dependent RNA Polymerase Regions of Human Norovirus GII.P17-GII.17 in 2013–2017,http://dx.doi.org/10.3389/fmicb.2019.02189,PMC6777354,31611853,CC BY,"Human norovirus (HuNoV) GII.P17-GII.17 (Kawasaki2014 variant) reportedly emerged in 2014 and caused gastroenteritis outbreaks worldwide. To clarify the evolution of both VP1 and RNA-dependent RNA polymerase (RdRp) regions of GII.P17-GII.17, we analyzed both global and novel Japanese strains detected during 2013–2017. Time-scaled phylogenetic trees revealed that the ancestral GII.17 VP1 region diverged around 1949, while the ancestral GII.P17 RdRp region diverged around 2010. The evolutionary rates of the VP1 and RdRp regions were estimated at ~2.7 × 10(−3) and ~2.3 × 10(−3) substitutions/site/year, respectively. The phylogenetic distances of the VP1 region exhibited no overlaps between intra-cluster and inter-cluster peaks in the GII.17 strains, whereas those of the RdRp region exhibited a unimodal distribution in the GII.P17 strains. Conformational epitope positions in the VP1 protein of the GII.P17-GII.17 strains were similar, although some substitutions, insertions and deletions had occurred. Strains belonging to the same cluster also harbored substitutions around the binding sites for the histo-blood group antigens of the VP1 protein. Moreover, some amino acid substitutions were estimated to be near the interface between monomers and the active site of the RdRp protein. These results suggest that the GII.P17-GII.17 virus has produced variants with the potential to alter viral antigenicity, host-binding capability, and replication property over the past 10 years.",2019 Sep 27,"['Matsushima, Yuki', 'Mizukoshi, Fuminori', 'Sakon, Naomi', 'Doan, Yen Hai', 'Ueki, Yo', 'Ogawa, Yasutaka', 'Motoya, Takumi', 'Tsukagoshi, Hiroyuki', 'Nakamura, Noriko', 'Shigemoto, Naoki', 'Yoshitomi, Hideaki', 'Okamoto-Nakagawa, Reiko', 'Suzuki, Rieko', 'Tsutsui, Rika', 'Terasoma, Fumio', 'Takahashi, Tomoko', 'Sadamasu, Kenji', 'Shimizu, Hideaki', 'Okabe, Nobuhiko', 'Nagasawa, Koo', 'Aso, Jumpei', 'Ishii, Haruyuki', 'Kuroda, Makoto', 'Ryo, Akihide', 'Katayama, Kazuhiko', 'Kimura, Hirokazu']",Front Microbiol,,,True
e4813a9f4fee2d74c954d90bed67e8738047a390,PMC,A Peptide-Based Virus Inactivator Protects Male Mice Against Zika Virus-Induced Damage of Testicular Tissue,http://dx.doi.org/10.3389/fmicb.2019.02250,PMC6777420,31611865,CC BY,"Zika virus (ZIKV) was a re-emerging arbovirus associated with Guillain–Barré Syndrome in adult and congenital Zika syndrome in fetus and infant. Although ZIKV was mainly transmitted by mosquito bites, many sexual transmission cases have been reported since the outbreak in 2015. ZIKV can persist in testis and semen for a long time, causing testicular tissue damage and reducing sperm quality. However, no drug has been approved for prevention or treatment of ZIKV infection, especially infection in male testicular tissue. Previously reported peptide Z2 could inactivate ZIKV, inhibiting ZIKV infection in vitro and in vivo. Importantly, Z2 could inhibit vertical transmission of ZIKV in pregnant mice, reducing ZIKV infection in fetus. Here we showed that intraperitoneally administered Z2 could also be distributed to testis and epididymis, resulting in the reduction of ZIKV RNA copies in testicular tissue and protection of testis and epididymis against ZIKV-induced pathological damage and poor sperm quality in type I interferon receptor-deficient A129 mice. Thus, Z2, a ZIKV inactivator, could serve as an antiviral agent for treatment of ZIKV infection and attenuation of ZIKV-induced testicular tissue damage.",2019 Sep 27,"['Si, Lulu', 'Meng, Yu', 'Tian, Fang', 'Li, Weihua', 'Zou, Peng', 'Wang, Qian', 'Xu, Wei', 'Wang, Yuzhu', 'Xia, Minjie', 'Hu, Jingying', 'Jiang, Shibo', 'Lu, Lu']",Front Microbiol,,,True
04510f144938a17bf2c2a9683ce3479ff0246b94,PMC,The protective role of microRNA-21 against coxsackievirus B3 infection through targeting the MAP2K3/P38 MAPK signaling pathway,http://dx.doi.org/10.1186/s12967-019-2077-y,PMC6778380,31585536,CC BY,"BACKGROUND: The P38 mitogen-activated protein kinase (MAPK) pathway plays an essential role in CVB3-induced diseases. We previously demonstrated microRNA-21 has potential inhibitory effect on the MAP2K3 which locates upstream of P38 MAPK and was upregulated in mouse hearts upon CVB3 infection. However, the effect and underlying mechanism of miRNA-21 on CVB3 infection remain unclear. METHODS: We detected continuous changes of cellular miRNA-21 and P38 MAPK proteins expression profiling post CVB3 infection in vitro within 12 h. P38 MAPK signaling was inhibited by the specific inhibitor, small interfering RNA and miRNA-21 mimic in vitro, CVB3 replication, cell apoptosis rate and proliferation were detected. Viral load in the mice heart, cardiomyocyte apoptosis rate and histological of the heart were also detected in the mice model of viral myocarditis pretreated with miRNA-21-lentivirus. RESULTS: We observed significant upregulation of miRNA-21 expression followed by suppression of the MAP2K3/P38 MAPK signaling in CVB3-infected Hela cells. The inactivation of the MAP2K3/P38 MAPK signaling by P38 MAPK specific inhibitor, small interfering RNA against MAP2K3, or miRNA-21 overexpression significantly inhibited viral progeny release from CVB3-infected cells. Mechanistically, when compared with control miRNA, miRNA-21 showed no effect on capsid protein VP1 expression and viral load within host cells, while significantly reversing CVB3-induced caspase-3 activation and cell apoptosis rate, further promoting proliferation of infected cells, which indicates the inhibitory effect of miRNA-21 on CVB3 progeny release. In the in vivo study, when compared with control miRNA, miRNA-21 pretreatment remarkably inactivated the MAP2K3/P38 MAPK signaling in mice and protected them against CVB3 infection as evidenced by significantly alleviated cell apoptosis rate, reduced viral titers, necrosis in the heart as well as by remarkably prolonged survival time. CONCLUSIONS: miRNA-21 were reverse correlated with P38 MAPK activation post CVB3 infection, miRNA-21 overexpression significantly inhibited viral progeny release and decreased myocytes apoptosis rate in vitro and in vivo, suggesting that miRNA-21 may serve as a potential therapeutic agent against CVB3 infection through targeting the MAP2K3/P38 MAPK signaling.",2019 Oct 4,"['He, Feng', 'Xiao, Zonghui', 'Yao, Hailan', 'Li, Sen', 'Feng, Miao', 'Wang, Wei', 'Liu, Zhewei', 'Liu, Zhuo', 'Wu, Jianxin']",J Transl Med,,,True
76b96ffbbdea59714eba9d891362ceb32731ad90,PMC,Tandem mass tag-based quantitative proteomic analysis of lycorine treatment in highly pathogenic avian influenza H5N1 virus infection,http://dx.doi.org/10.7717/peerj.7697,PMC6778435,31592345,CC BY,"Highly pathogenic H5N1 influenza viruses (HPAIV) cause rapid systemic illness and death in susceptible animals, leading to a disease with high morbidity and mortality rates. Although vaccines and drugs are the best solution to prevent this threat, a more effective treatment for H5 strains of influenza has yet to be developed. Therefore, the development of therapeutics/drugs that combat H5N1 influenza virus infection is becoming increasingly important. Lycorine, the major component of Amaryllidaceae alkaloids, exhibits better protective effects against A/CK/GD/178/04 (H5N1) (GD178) viruses than the commercial neuraminidase (NA) inhibitor oseltamivir in our prior study. Lycorine demonstrates outstanding antiviral activity because of its inhibitory activity against the export of viral ribonucleoprotein complexes (vRNPs) from the nucleus. However, how lycorine affects the proteome of AIV infected cells is unknown. Therefore, we performed a comparative proteomic analysis to identify changes in protein expression in AIV-infected Madin-Darby Canine Kidney cells treated with lycorine. Three groups were designed: mock infection group (M), virus infection group (V), and virus infection and lycorine-treated after virus infection group (L). The multiplexed tandem mass tag (TMT) approach was employed to analyze protein level in this study. In total, 5,786 proteins were identified from the three groups of cells by using TMT proteomic analysis. In the V/M group, 1,101 proteins were identified, of which 340 differentially expressed proteins (DEPs) were determined during HPAIV infection; among the 1,059 proteins identified from the lycorine-treated group, 258 proteins presented significant change. Here, 71 proteins showed significant upregulation or downregulation of expression in the virus-infected/mock and virus-infected/lycorine-treated comparisons, and the proteins in each fraction were functionally classified further. Interestingly, lycorine treatment decreased the levels of the nuclear pore complex protein 93 (Nup93, E2RSV7), which is associated with nuclear–cytoplasmic transport. In addition, Western blot experiments confirmed that the expression of Nup93 was significantly downregulated in lycorine treatment but induced after viral infection. Our results may provide new insights into how lycorine may trap vRNPs in the nucleus and suggest new potential therapeutic targets for influenza virus.",2019 Oct 2,"['Yang, Li', 'Zhang, Jia Hao', 'Zhang, Xiao Li', 'Lao, Guang Jie', 'Su, Guan Ming', 'Wang, Lei', 'Li, Yao Lan', 'Ye, Wen Cai', 'He, Jun']",PeerJ,,,True
e4b641feebcb6d2c1c6b6ce1132007951f75f84a,PMC,Tandem mass tag-based quantitative proteomic analysis of lycorine treatment in highly pathogenic avian influenza H5N1 virus infection,http://dx.doi.org/10.7717/peerj.7697,PMC6778435,31592345,CC BY,"Highly pathogenic H5N1 influenza viruses (HPAIV) cause rapid systemic illness and death in susceptible animals, leading to a disease with high morbidity and mortality rates. Although vaccines and drugs are the best solution to prevent this threat, a more effective treatment for H5 strains of influenza has yet to be developed. Therefore, the development of therapeutics/drugs that combat H5N1 influenza virus infection is becoming increasingly important. Lycorine, the major component of Amaryllidaceae alkaloids, exhibits better protective effects against A/CK/GD/178/04 (H5N1) (GD178) viruses than the commercial neuraminidase (NA) inhibitor oseltamivir in our prior study. Lycorine demonstrates outstanding antiviral activity because of its inhibitory activity against the export of viral ribonucleoprotein complexes (vRNPs) from the nucleus. However, how lycorine affects the proteome of AIV infected cells is unknown. Therefore, we performed a comparative proteomic analysis to identify changes in protein expression in AIV-infected Madin-Darby Canine Kidney cells treated with lycorine. Three groups were designed: mock infection group (M), virus infection group (V), and virus infection and lycorine-treated after virus infection group (L). The multiplexed tandem mass tag (TMT) approach was employed to analyze protein level in this study. In total, 5,786 proteins were identified from the three groups of cells by using TMT proteomic analysis. In the V/M group, 1,101 proteins were identified, of which 340 differentially expressed proteins (DEPs) were determined during HPAIV infection; among the 1,059 proteins identified from the lycorine-treated group, 258 proteins presented significant change. Here, 71 proteins showed significant upregulation or downregulation of expression in the virus-infected/mock and virus-infected/lycorine-treated comparisons, and the proteins in each fraction were functionally classified further. Interestingly, lycorine treatment decreased the levels of the nuclear pore complex protein 93 (Nup93, E2RSV7), which is associated with nuclear–cytoplasmic transport. In addition, Western blot experiments confirmed that the expression of Nup93 was significantly downregulated in lycorine treatment but induced after viral infection. Our results may provide new insights into how lycorine may trap vRNPs in the nucleus and suggest new potential therapeutic targets for influenza virus.",2019 Oct 2,"['Yang, Li', 'Zhang, Jia Hao', 'Zhang, Xiao Li', 'Lao, Guang Jie', 'Su, Guan Ming', 'Wang, Lei', 'Li, Yao Lan', 'Ye, Wen Cai', 'He, Jun']",PeerJ,,,False
ccb33929d203954acdf6022791f7b782f9f9dfe3,PMC,Tandem mass tag-based quantitative proteomic analysis of lycorine treatment in highly pathogenic avian influenza H5N1 virus infection,http://dx.doi.org/10.7717/peerj.7697,PMC6778435,31592345,CC BY,"Highly pathogenic H5N1 influenza viruses (HPAIV) cause rapid systemic illness and death in susceptible animals, leading to a disease with high morbidity and mortality rates. Although vaccines and drugs are the best solution to prevent this threat, a more effective treatment for H5 strains of influenza has yet to be developed. Therefore, the development of therapeutics/drugs that combat H5N1 influenza virus infection is becoming increasingly important. Lycorine, the major component of Amaryllidaceae alkaloids, exhibits better protective effects against A/CK/GD/178/04 (H5N1) (GD178) viruses than the commercial neuraminidase (NA) inhibitor oseltamivir in our prior study. Lycorine demonstrates outstanding antiviral activity because of its inhibitory activity against the export of viral ribonucleoprotein complexes (vRNPs) from the nucleus. However, how lycorine affects the proteome of AIV infected cells is unknown. Therefore, we performed a comparative proteomic analysis to identify changes in protein expression in AIV-infected Madin-Darby Canine Kidney cells treated with lycorine. Three groups were designed: mock infection group (M), virus infection group (V), and virus infection and lycorine-treated after virus infection group (L). The multiplexed tandem mass tag (TMT) approach was employed to analyze protein level in this study. In total, 5,786 proteins were identified from the three groups of cells by using TMT proteomic analysis. In the V/M group, 1,101 proteins were identified, of which 340 differentially expressed proteins (DEPs) were determined during HPAIV infection; among the 1,059 proteins identified from the lycorine-treated group, 258 proteins presented significant change. Here, 71 proteins showed significant upregulation or downregulation of expression in the virus-infected/mock and virus-infected/lycorine-treated comparisons, and the proteins in each fraction were functionally classified further. Interestingly, lycorine treatment decreased the levels of the nuclear pore complex protein 93 (Nup93, E2RSV7), which is associated with nuclear–cytoplasmic transport. In addition, Western blot experiments confirmed that the expression of Nup93 was significantly downregulated in lycorine treatment but induced after viral infection. Our results may provide new insights into how lycorine may trap vRNPs in the nucleus and suggest new potential therapeutic targets for influenza virus.",2019 Oct 2,"['Yang, Li', 'Zhang, Jia Hao', 'Zhang, Xiao Li', 'Lao, Guang Jie', 'Su, Guan Ming', 'Wang, Lei', 'Li, Yao Lan', 'Ye, Wen Cai', 'He, Jun']",PeerJ,,,False
6d33e8387fbdbff5a349ec0e5819bd02b3a0780c,PMC,Tandem mass tag-based quantitative proteomic analysis of lycorine treatment in highly pathogenic avian influenza H5N1 virus infection,http://dx.doi.org/10.7717/peerj.7697,PMC6778435,31592345,CC BY,"Highly pathogenic H5N1 influenza viruses (HPAIV) cause rapid systemic illness and death in susceptible animals, leading to a disease with high morbidity and mortality rates. Although vaccines and drugs are the best solution to prevent this threat, a more effective treatment for H5 strains of influenza has yet to be developed. Therefore, the development of therapeutics/drugs that combat H5N1 influenza virus infection is becoming increasingly important. Lycorine, the major component of Amaryllidaceae alkaloids, exhibits better protective effects against A/CK/GD/178/04 (H5N1) (GD178) viruses than the commercial neuraminidase (NA) inhibitor oseltamivir in our prior study. Lycorine demonstrates outstanding antiviral activity because of its inhibitory activity against the export of viral ribonucleoprotein complexes (vRNPs) from the nucleus. However, how lycorine affects the proteome of AIV infected cells is unknown. Therefore, we performed a comparative proteomic analysis to identify changes in protein expression in AIV-infected Madin-Darby Canine Kidney cells treated with lycorine. Three groups were designed: mock infection group (M), virus infection group (V), and virus infection and lycorine-treated after virus infection group (L). The multiplexed tandem mass tag (TMT) approach was employed to analyze protein level in this study. In total, 5,786 proteins were identified from the three groups of cells by using TMT proteomic analysis. In the V/M group, 1,101 proteins were identified, of which 340 differentially expressed proteins (DEPs) were determined during HPAIV infection; among the 1,059 proteins identified from the lycorine-treated group, 258 proteins presented significant change. Here, 71 proteins showed significant upregulation or downregulation of expression in the virus-infected/mock and virus-infected/lycorine-treated comparisons, and the proteins in each fraction were functionally classified further. Interestingly, lycorine treatment decreased the levels of the nuclear pore complex protein 93 (Nup93, E2RSV7), which is associated with nuclear–cytoplasmic transport. In addition, Western blot experiments confirmed that the expression of Nup93 was significantly downregulated in lycorine treatment but induced after viral infection. Our results may provide new insights into how lycorine may trap vRNPs in the nucleus and suggest new potential therapeutic targets for influenza virus.",2019 Oct 2,"['Yang, Li', 'Zhang, Jia Hao', 'Zhang, Xiao Li', 'Lao, Guang Jie', 'Su, Guan Ming', 'Wang, Lei', 'Li, Yao Lan', 'Ye, Wen Cai', 'He, Jun']",PeerJ,,,False
26f8c5fbd310c95c2e1fb04c34ed6f5d10901d07,PMC,Evaluating the potential impact of targeted vaccination strategies against severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks in the healthcare setting,http://dx.doi.org/10.1186/s12976-019-0112-6,PMC6778978,31587665,CC BY,"BACKGROUND: Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are two coronaviruses with demonstrated potential to generate significant nosocomial outbreaks. In particular, MERS continues to pose a significant threat in the Middle East since 2012. Currently, no licensed vaccine or drug treatment is available to treat patients infected with either coronavirus. However, there are some MERS vaccines in the preclinical stage of development. We sought to evaluate the potential impact of targeted vaccination strategies for mitigating SARS and MERS outbreaks in healthcare settings using simple mathematical models and detailed historic transmission trees describing the progression of past nosocomial outbreaks of SARS and MERS. RESULTS: Our findings suggest that vaccination strategies targeting patients and healthcare workers, which have been disproportionately affected during past outbreaks, and assuming two vaccination coverage levels at 50 and 75% have the potential to avert nearly 50% or more of MERS or SARS cases. CONCLUSION: Our modeling results informed by historic outbreak data for SARS and MERS suggest that vaccination strategies targeting patients could be an effective measure to mitigate and prevent outbreaks in the healthcare setting. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12976-019-0112-6) contains supplementary material, which is available to authorized users.",2019 Oct 7,"['Abdirizak, Fatima', 'Lewis, Rayleen', 'Chowell, Gerardo']",Theor Biol Med Model,,,True
150e648964270067a1ea14caffbc3427f756dafb,PMC,Epidemiological and Evolutionary Analysis of Dengue-1 Virus Detected in Guangdong during 2014: Recycling of Old and Formation of New Lineages,http://dx.doi.org/10.4269/ajtmh.18-0951,PMC6779206,31392945,CC BY,"The incidence of dengue is increasing in Guangdong, China, with the largest outbreak to date in 2014. Widespread awareness of epidemiological and molecular characteristics of the dengue virus (DENV) is required. In 2014, we isolated the virus from patients and sequenced its genome. The sequences of DENV isolated from Guangdong and other countries screened since 2005 were studied to establish molecular evolutionary databases along with epidemiological data to explore its epidemiological, phylogenetic, and molecular characteristics. Causes underlying the occurrence of the dengue epidemic included importation and localization of the virus. The number of indigenous cases significantly exceeded that of imported cases. Dengue virus 1 is the most important serotype and caused the long-term epidemic locally. Based on the data available since 2005, DENV1 was divided into three genotypes (I, IV, and V). Only genotypes I and V were detected in 2014. In 2014, an epidemic involving old lineages of DENV1 genotype V occurred after 2 years of silence. The genotype was previously detected from 2009 to 2011. Genotype I, which caused recent epidemics, demonstrated a continuation of new lineages, and a predictive pattern of molecular evolution since 2005 among the four lineages was present. The DENV isolated from Guangdong was closely related to those causing large-scale epidemics in neighboring countries, suggesting the possibility of its import from these countries. The lack of sufficient epidemiological data and evidence on the local mosquito-borne DENV emphasizes the importance of studying the molecular evolutionary features and establishing a well-established phylogenetic tree for dengue prevention and control in Guangdong.",2019 Oct 5,"['Yu, Jianhai', 'Li, Xujuan', 'He, Xiaoen', 'Liu, Xuling', 'Zhong, Zhicheng', 'Xie, Qian', 'Zhu, Li', 'Jia, Fengyun', 'Mao, Yingxue', 'Chen, Zongqiu', 'Wen, Ying', 'Ma, Danjuan', 'Yu, Linzhong', 'Zhang, Bao', 'Zhao, Wei', 'Xiao, Weiwei']",Am J Trop Med Hyg,,,True
cf12680358351109a975a23165bbb48620b578a5,PMC,Development of a recombinant replication-deficient rabies virus-based bivalent-vaccine against MERS-CoV and rabies virus and its humoral immunogenicity in mice,http://dx.doi.org/10.1371/journal.pone.0223684,PMC6779238,31589656,CC BY,"Middle East respiratory syndrome-coronavirus (MERS-CoV) is an emerging virus that causes severe disease with fatal outcomes; however, there are currently no approved vaccines or specific treatments against MERS-CoV. Here, we developed a novel bivalent vaccine against MERS-CoV and rabies virus (RV) using the replication-incompetent P-gene-deficient RV (RVΔP), which has been previously established as a promising and safe viral vector. MERS-CoV spike glycoprotein comprises S1 and S2 subunits, with the S1 subunit being a primary target of neutralizing antibodies. Recombinant RVΔP, which expresses S1 fused with transmembrane and cytoplasmic domains together with 14 amino acids from the ectodomains of the RV-glycoprotein (RV-G), was developed using a reverse genetics method and named RVΔP-MERS/S1. Following generation of RVΔP-MERS/S1 and RVΔP, our analysis revealed that they shared similar growth properties, with the expression of S1 in RVΔP-MERS/S1-infected cells confirmed by immunofluorescence and western blot, and the immunogenicity and pathogenicity evaluated using mouse infection experiments. We observed no rabies-associated signs or symptoms in mice inoculated with RVΔP-MERS/S1. Moreover, virus-specific neutralizing antibodies against both MERS-CoV and RV were induced in mice inoculated intraperitoneally with RVΔP-MERS/S1. These findings indicate that RVΔP-MERS/S1 is a promising and safe bivalent-vaccine candidate against both MERS-CoV and RV.",2019 Oct 7,"['Kato, Hirofumi', 'Takayama-Ito, Mutsuyo', 'Iizuka-Shiota, Itoe', 'Fukushi, Shuetsu', 'Posadas-Herrera, Guillermo', 'Horiya, Madoka', 'Satoh, Masaaki', 'Yoshikawa, Tomoki', 'Yamada, Souichi', 'Harada, Shizuko', 'Fujii, Hikaru', 'Shibamura, Miho', 'Inagaki, Takuya', 'Morimoto, Kinjiro', 'Saijo, Masayuki', 'Lim, Chang-Kweng']",PLoS One,,,True
8d0367ee4b4bcd6fea276d8daa9bd2f50e401a34,PMC,Human virome in nasopharynx and tracheal secretion samples,http://dx.doi.org/10.1590/0074-02760190198,PMC6779266,31596309,CC BY,"BACKGROUND: In Brazil the implementation of the Sentinel Surveillance System of Influenza began in 2000. Central public health laboratories use reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for diagnosis of respiratory viruses, but this protocol identifies only specific targets, resulted in inconclusive diagnosis for many samples. Thus, high-throughput sequencing (HTS) would be complementary method in the identification of pathogens in inconclusive samples for RT-qPCR or other specific detection protocols. OBJECTIVES: This study aimed to detect unidentified viruses using HTS approach in negative samples of nasopharynx/tracheal secretions by the standard RT-qPCR collected in the Federal District, Brazil. METHODS: Nucleic acids were extracted from samples collected in winter period of 2016 and subjected to HTS. The results were confirmed by the multiplex PR21 RT-qPCR, which identifies 21 respiratory pathogens. FINDINGS: The main viruses identified by HTS were of families Herpesviridae, Coronaviridae, Parvoviridae and Picornaviridae, with the emphasis on rhinoviruses. The presence of respiratory viruses in the samples was confirmed by the PR21 multiplex RT-qPCR. Coronavirus, enterovirus, bocavirus and rhinovirus were found by multiplex RT-qPCR as well as by HTS analyses. MAIN CONCLUSIONS: Wide virus diversity was found by different methodologies and high frequency of rhinovirus occurrence was confirmed in population in winter, showing its relevance for public health.",2019 Oct 3,"['Souza, Larissa da Costa', 'Blawid, Rosana', 'Silva, João Marcos Fagundes', 'Nagata, Tatsuya']",Mem Inst Oswaldo Cruz,,,True
5b6a62811eb3feb32f20a0193f43c435292fb6ec,PMC,Human virome in nasopharynx and tracheal secretion samples,http://dx.doi.org/10.1590/0074-02760190198,PMC6779266,31596309,CC BY,"BACKGROUND: In Brazil the implementation of the Sentinel Surveillance System of Influenza began in 2000. Central public health laboratories use reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for diagnosis of respiratory viruses, but this protocol identifies only specific targets, resulted in inconclusive diagnosis for many samples. Thus, high-throughput sequencing (HTS) would be complementary method in the identification of pathogens in inconclusive samples for RT-qPCR or other specific detection protocols. OBJECTIVES: This study aimed to detect unidentified viruses using HTS approach in negative samples of nasopharynx/tracheal secretions by the standard RT-qPCR collected in the Federal District, Brazil. METHODS: Nucleic acids were extracted from samples collected in winter period of 2016 and subjected to HTS. The results were confirmed by the multiplex PR21 RT-qPCR, which identifies 21 respiratory pathogens. FINDINGS: The main viruses identified by HTS were of families Herpesviridae, Coronaviridae, Parvoviridae and Picornaviridae, with the emphasis on rhinoviruses. The presence of respiratory viruses in the samples was confirmed by the PR21 multiplex RT-qPCR. Coronavirus, enterovirus, bocavirus and rhinovirus were found by multiplex RT-qPCR as well as by HTS analyses. MAIN CONCLUSIONS: Wide virus diversity was found by different methodologies and high frequency of rhinovirus occurrence was confirmed in population in winter, showing its relevance for public health.",2019 Oct 3,"['Souza, Larissa da Costa', 'Blawid, Rosana', 'Silva, João Marcos Fagundes', 'Nagata, Tatsuya']",Mem Inst Oswaldo Cruz,,,False
e8ae86b48db5e9860652f9c78c61f13c1b41c700,PMC,Zinc Chelation Specifically Inhibits Early Stages of Dengue Virus Replication by Activation of NF-κB and Induction of Antiviral Response in Epithelial Cells,http://dx.doi.org/10.3389/fimmu.2019.02347,PMC6779808,31632411,CC BY,"Zinc is an essential micronutrient which regulates diverse physiological functions and has been shown to play a crucial role in viral infections. Zinc has a necessary role in the replication of many viruses, however, antiviral action of zinc has also been demonstrated in in vitro infection models most likely through induction of host antiviral responses. Therefore, depending on the host machinery that the virus employs at different stages of infection, zinc may either facilitate, or inhibit virus infection. In this study, we show that zinc plays divergent roles in rotavirus and dengue virus infections in epithelial cells. Dengue virus infection did not perturb the epithelial barrier functions despite the release of virus from the basolateral surface whereas rotavirus infection led to disruption of epithelial junctions. In rotavirus infection, zinc supplementation post-infection did not block barrier disruption suggesting that zinc does not affect rotavirus life-cycle or protects epithelial barriers post-infection suggesting the involvement of cellular pathways in the beneficial effect of zinc supplementation in enteric infections. Zinc depletion by N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN) inhibited dengue virus and Japanese encephalitis virus (JEV) infection but had no effect on rotavirus. Time-of-addition experiments suggested that zinc chelation affected both early and late stages of dengue virus infectious cycle and zinc chelation abrogated dengue virus RNA replication. We show that transient zinc chelation induces ER stress and antiviral response by activating NF-kappaB leading to induction of interferon signaling. These results suggest that modulation of zinc homeostasis during virus infection could be a component of host antiviral response and altering zinc homeostasis may act as a potent antiviral strategy against flaviviruses.",2019 Oct 1,"['Kar, Meenakshi', 'Khan, Naseem Ahmed', 'Panwar, Aleksha', 'Bais, Sachendra S.', 'Basak, Soumen', 'Goel, Renu', 'Sopory, Shailaja', 'Medigeshi, Guruprasad R.']",Front Immunol,,,True
36bb7f8a45356e1a6d2da97b78155d0d45646cc0,PMC,Disparate Entry of Adenoviruses Dictates Differential Innate Immune Responses on the Ocular Surface,http://dx.doi.org/10.3390/microorganisms7090351,PMC6780103,31540200,CC BY,"Human adenovirus infection of the ocular surface is associated with severe keratoconjunctivitis and the formation of subepithelial corneal infiltrates, which may persist and impair vision for months to years following infection. Long term pathology persists well beyond the resolution of viral replication, indicating that the prolonged immune response is not virus-mediated. However, it is not clear how these responses are sustained or even initiated following infection. This review discusses recent work from our laboratory and others which demonstrates different entry pathways specific to both adenovirus and cell type. These findings suggest that adenoviruses may stimulate specific pattern recognition receptors in an entry/trafficking-dependent manner, leading to distinct immune responses dependent on the virus/cell type combination. Additional work is needed to understand the specific connections between adenoviral entry and the stimulation of innate immune responses by the various cell types present on the ocular surface.",2019 Sep 13,"['Pennington, Matthew R.', 'Saha, Amrita', 'Painter, David F.', 'Gavazzi, Christina', 'Ismail, Ashrafali M.', 'Zhou, Xiaohong', 'Chodosh, James', 'Rajaiya, Jaya']",Microorganisms,,,True
01be6aef7ae6555eef2062bddb57f8643d1244e9,PMC,"Antiviral Activity of Exopolysaccharides Produced by Lactic Acid Bacteria of the Genera Pediococcus, Leuconostoc and Lactobacillus against Human Adenovirus Type 5",http://dx.doi.org/10.3390/medicina55090519,PMC6780409,31443536,CC BY,"Background and objectives: The use of antagonistic probiotic microorganisms and their byproducts represents a promising approach for the treatment of viral diseases. In the current work, the effect of exopolysaccharides (EPSs) produced by lactic acid bacteria from different genera on the structural and functional characteristics of cells and the development of adenoviral infection in vitro was studied. Materials and Methods: Cytotoxicity of six EPSs of lactic acid bacteria of the genera Lactobacillus, Leuconostoc and Pediococcus was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. The influence of the EPSs on the infectivity of human adenovirus type 5 (HAdV-5) and on the cell cycle under a condition of adenovirus infection was studied using plaque reduction assay and flow cytometric analysis, respectively. Results: It was shown that exopolysaccharides were non-toxic to Madin-Darby bovine kidney cells (MDBK) as they reduced their viability by 3–17%. A change in the distribution of the cell cycle phases in the non-infected cell population treated with EPSs was observed. The analysis demonstrated an increase in the number of cells in the S phase by 47% when using EPSs 15a and a decrease in the number of cells in the G1 phase by 20–27% when treated with the EPSs 15a, 33a, and 19s. The use of EPSs did not led to the normalization of the life cycle of HAdV-5 infected cells to the level of non-infected cells. The EPSs showed low virucidal activity and reduced the HAdV-5 infectivity to 85%. Among the studied exopolysaccharides, anti-adenovirus activity was found for EPS 26a that is produced by Lactobacillus spp. strain. The treatment of cells with the EPS following virus adsorption completely (100%) suppressed the formation and release of HAdV-5 infectious. Conclusions: EPS 26a possessed distinct anti-HAdV-5 activity and the obtained data demonstrate the potential of using exopolysaccharides as anti-adenoviral agents.",2019 Aug 22,"['Biliavska, Liubov', 'Pankivska, Yulia', 'Povnitsa, Olga', 'Zagorodnya, Svitlana']",Medicina (Kaunas),,,True
bd9937d46e1e7947e28497ca098b76703981d2d9,PMC,"Impact of an Infectious Disease Specialist on an Antimicrobial Stewardship Program at a Resource-Limited, Non-Academic Community Hospital in Korea",http://dx.doi.org/10.3390/jcm8091293,PMC6780603,31450837,CC BY,"Background: Implementing a successful antimicrobial stewardship program (ASP) is difficult for non-academic community (NAC) hospitals due to insufficient infrastructure. Aim: We evaluated the impact of an infectious disease specialist (IDS) on implementing an ASP in a resource-limited setting in Korea. Methods: A retrospective study was performed at a NAC hospital between June 2015 and August 2018. An IDS has led an ASP at the hospital since June 2017. We used an interrupted time series analysis to evaluate longitudinal effects of the IDS-led ASP on the amount of antibiotic use and incidence of multidrug-resistant organism (MDRO) acquisition. Findings: Total antibiotic use changed from 698.82 ± 74.41 to 602.09 ± 69.94 defined daily dose/1000 patient-days (PDs) after intervention. An immediate reduction in the use of carbapenems, glycopeptides, penicillins, and other antibiotics followed the IDS-led ASP. The 3rd/4th generation cephalosporins and carbapenems prescription rates decreased in slope after the intervention. Incidence of MDRO acquisition changed from 1.38, 0.78, and 0.21/1000 PDs to 1.06, 0.15, and 0.32/1000 PDs in methicillin-resistant Staphylococcus aureus, multidrug-resistant Acinetobacter baumannii, and multidrug-resistant Pseudomonas aeruginosa, respectively. The incidence of methicillin-resistant Staphylococcus aureus and multidrug-resistant Acinetobacter baumannii acquisition immediately decreased following intervention. Conclusion: An IDS can implement a successful ASP by reducing antibiotic consumption and MDRO acquisition at resource-limited NAC hospitals.",2019 Aug 23,"['Kim, Yong Chan', 'Kim, Eun Jin', 'Heo, Jung Yeon', 'Choi, Young Hwa', 'Ahn, Jin Young', 'Jeong, Su Jin', 'Ku, Nam Su', 'Choi, Jun Yong', 'Yeom, Joon-sup', 'Kim, Ha Yan']",J Clin Med,,,True
17b56b4742fcfc1cea6170a61ffd5c06bd0fbab1,PMC,"Impact of an Infectious Disease Specialist on an Antimicrobial Stewardship Program at a Resource-Limited, Non-Academic Community Hospital in Korea",http://dx.doi.org/10.3390/jcm8091293,PMC6780603,31450837,CC BY,"Background: Implementing a successful antimicrobial stewardship program (ASP) is difficult for non-academic community (NAC) hospitals due to insufficient infrastructure. Aim: We evaluated the impact of an infectious disease specialist (IDS) on implementing an ASP in a resource-limited setting in Korea. Methods: A retrospective study was performed at a NAC hospital between June 2015 and August 2018. An IDS has led an ASP at the hospital since June 2017. We used an interrupted time series analysis to evaluate longitudinal effects of the IDS-led ASP on the amount of antibiotic use and incidence of multidrug-resistant organism (MDRO) acquisition. Findings: Total antibiotic use changed from 698.82 ± 74.41 to 602.09 ± 69.94 defined daily dose/1000 patient-days (PDs) after intervention. An immediate reduction in the use of carbapenems, glycopeptides, penicillins, and other antibiotics followed the IDS-led ASP. The 3rd/4th generation cephalosporins and carbapenems prescription rates decreased in slope after the intervention. Incidence of MDRO acquisition changed from 1.38, 0.78, and 0.21/1000 PDs to 1.06, 0.15, and 0.32/1000 PDs in methicillin-resistant Staphylococcus aureus, multidrug-resistant Acinetobacter baumannii, and multidrug-resistant Pseudomonas aeruginosa, respectively. The incidence of methicillin-resistant Staphylococcus aureus and multidrug-resistant Acinetobacter baumannii acquisition immediately decreased following intervention. Conclusion: An IDS can implement a successful ASP by reducing antibiotic consumption and MDRO acquisition at resource-limited NAC hospitals.",2019 Aug 23,"['Kim, Yong Chan', 'Kim, Eun Jin', 'Heo, Jung Yeon', 'Choi, Young Hwa', 'Ahn, Jin Young', 'Jeong, Su Jin', 'Ku, Nam Su', 'Choi, Jun Yong', 'Yeom, Joon-sup', 'Kim, Ha Yan']",J Clin Med,,,False
7bbe8c4f7a911194a8901fb24e87204b508e7715,PMC,Vδ2 T-Cells Kill ZIKV-Infected Cells by NKG2D-Mediated Cytotoxicity,http://dx.doi.org/10.3390/microorganisms7090350,PMC6781265,31547470,CC BY,"An expansion of effector/activated Vδ2 T-cells was recently described in acute Zika virus (ZIKV)-infected patients, but their role in the protective immune response was not clarified. The aim of this study was to define the antiviral activity of Vδ2 T-cells against ZIKV-infected cells. The Vδ2 T-cells expansion and their cytotoxic activity against ZIKV-infected cells were tested in vitro and analyzed by RT-PCR and flow cytometry. We found that ZIKV infection was able to induce Vδ2 T-cells expansion and sensitized A549 cells to Vδ2-mediated killing. Indeed, expanded Vδ2 T-cells killed ZIKV-infected cells through degranulation and perforin release. Moreover, ZIKV infection was able to increase the expression on A549 cells of NKG2D ligands (NKG2DLs), namely MICA, MICB, and ULBP2, at both the mRNA and protein levels, suggesting the possible involvement of these molecules in the recognition by NKG2D-expressing Vδ2 T-cells. Indeed, the killing of ZIKV-infected cells by expanded Vδ2 T-cells was mediated by NKG2D/NKG2DL interaction as NKG2D neutralization abrogated Vδ2 cytotoxicity. Our data showed a strong antiviral activity of Vδ2 T-cells against ZIKV-infected cells, suggesting their involvement in the protective immune response. Other studies are necessary to investigate whether the lack of Vδ2 T-cells expansion in vivo may be associated with disease complications.",2019 Sep 12,"['Cimini, Eleonora', 'Sacchi, Alessandra', 'De Minicis, Sara', 'Bordoni, Veronica', 'Casetti, Rita', 'Grassi, Germana', 'Colavita, Francesca', 'Castilletti, Concetta', 'Capobianchi, Maria Rosaria', 'Ippolito, Giuseppe', 'Desimio, Maria Giovanna', 'Doria, Margherita', 'Agrati, Chiara']",Microorganisms,,,True
585e27107bd360c6d5a6519bbafe7006a1ce7cce,PMC,Comprehensive Analysis of the Safety Profile of a Single-Stranded RNA Nano-Structure Adjuvant,http://dx.doi.org/10.3390/pharmaceutics11090464,PMC6781302,31500241,CC BY,"Adjuvants enhance the efficacy of vaccines by stimulating immune response-related gene expression and pathways. Although some adjuvants have been approved for commercial use in human vaccines (e.g., Alum, MF59, and AS03), they might elicit adverse side effects, such as autoimmune diseases. Recently, we developed a novel single-stranded RNA (ssRNA) nano-structure adjuvant, which can stimulate both Th1 and Th2 responses. In this study, we evaluated the safety and toxicological profiles of this ssRNA nano-structure adjuvant in vitro and in vivo. Mice were intramuscularly immunized with the ssRNA nano-structure adjuvant three times, once every 2 weeks. The results indicate no significant differences in hematological and serum biochemistry parameters between the ssRNA-treated groups and the control group. From a histopathological perspective, no evidence of tissue damage was found in any group. The levels of IgE and anti-nuclear antibodies, which are markers of autoimmune disease, were not different between the ssRNA-treated groups and the control group. The findings of this study suggest that the ssRNA nano-structure can be used as a safe adjuvant to increase vaccine efficacies.",2019 Sep 7,"['Park, Hyeong-Jun', 'Ko, Hae Li', 'Won, Dong-Hoon', 'Hwang, Da-Bin', 'Shin, Yoo-Sub', 'Kwak, Hye-Won', 'Kim, Hye-Jung', 'Yun, Jun-Won', 'Nam, Jae-Hwan']",Pharmaceutics,,,True
6fed47e670b39c02abfa32b11b8107c1079b378a,PMC,Comprehensive Analysis of the Safety Profile of a Single-Stranded RNA Nano-Structure Adjuvant,http://dx.doi.org/10.3390/pharmaceutics11090464,PMC6781302,31500241,CC BY,"Adjuvants enhance the efficacy of vaccines by stimulating immune response-related gene expression and pathways. Although some adjuvants have been approved for commercial use in human vaccines (e.g., Alum, MF59, and AS03), they might elicit adverse side effects, such as autoimmune diseases. Recently, we developed a novel single-stranded RNA (ssRNA) nano-structure adjuvant, which can stimulate both Th1 and Th2 responses. In this study, we evaluated the safety and toxicological profiles of this ssRNA nano-structure adjuvant in vitro and in vivo. Mice were intramuscularly immunized with the ssRNA nano-structure adjuvant three times, once every 2 weeks. The results indicate no significant differences in hematological and serum biochemistry parameters between the ssRNA-treated groups and the control group. From a histopathological perspective, no evidence of tissue damage was found in any group. The levels of IgE and anti-nuclear antibodies, which are markers of autoimmune disease, were not different between the ssRNA-treated groups and the control group. The findings of this study suggest that the ssRNA nano-structure can be used as a safe adjuvant to increase vaccine efficacies.",2019 Sep 7,"['Park, Hyeong-Jun', 'Ko, Hae Li', 'Won, Dong-Hoon', 'Hwang, Da-Bin', 'Shin, Yoo-Sub', 'Kwak, Hye-Won', 'Kim, Hye-Jung', 'Yun, Jun-Won', 'Nam, Jae-Hwan']",Pharmaceutics,,,False
2d21f74120d056518c96f23fc9df39320c2d598a,PMC,"Enterovirus D68-associated respiratory and neurological illness in Spain, 2014–2018",http://dx.doi.org/10.1080/22221751.2019.1668243,PMC6781473,31571527,CC BY,"During 2014, enterovirus D68 (EV-D68) outbreaks were described globally, causing severe respiratory diseases in children and, in some cases, subsequent paralysis. In this study, the type characterization of enterovirus (EV) detected in respiratory illnesses and the epidemiology and clinical association of EV-D68 infections in Spain over a five-year period were described. A total of 546 EV-positive samples from hospitalized patients with respiratory infections were included. EV-D68 was the most frequently detected type (46.6%, 191/410 typed EV). Other EV from species A (25.1%), B (27.8%) and C (0.5%) were also identified. EV-D68 infections were more associated with bronchitis while EV-A/B types were more frequent in upper respiratory illness (p < 0.01). EV-D68 was also detected in patients with neurological symptoms (nine meningitis/meningoencephalitis and eight acute flaccid paralysis cases). Phylogenetic analysis of 3′-VP1 region showed most Spanish EV-D68 sequences from 2014 to 2016 belonged to subclades B2/B3, as other American and European strains circulating during the same period. However, those detected in 2017 and 2018 clustered to the emerged subclade D1. In summary, different EV can cause respiratory infections but EV-D68 was the most prevalent, with several strains circulating in Spain at least since 2014. Association between EV-D68 infection and neurological disease was also described.",2019 Oct 1,"['González-Sanz, Rubén', 'Taravillo, Irene', 'Reina, Jordi', 'Navascués, Ana', 'Moreno-Docón, Antonio', 'Aranzamendi, Maitane', 'Romero, María Pilar', 'del Cuerpo, Margarita', 'Pérez-González, Carmen', 'Pérez-Castro, Sonia', 'Otero, Almudena', 'Cabrerizo, María']",Emerg Microbes Infect,,,True
8e29fa03ad2ae833e99f41652cc543877d415c44,PMC,Syrian Hamster as an Animal Model for the Study on Infectious Diseases,http://dx.doi.org/10.3389/fimmu.2019.02329,PMC6781508,31632404,CC BY,"Infectious diseases still remain one of the biggest challenges for human health. In order to gain a better understanding of the pathogenesis of infectious diseases and develop effective diagnostic tools, therapeutic agents, and preventive vaccines, a suitable animal model which can represent the characteristics of infectious is required. The Syrian hamster immune responses to infectious pathogens are similar to humans and as such, this model is advantageous for studying pathogenesis of infection including post-bacterial, viral and parasitic pathogens, along with assessing the efficacy and interactions of medications and vaccines for those pathogens. This review summarizes the current status of Syrian hamster models and their use for understanding the underlying mechanisms of pathogen infection, in addition to their use as a drug discovery platform and provides a strong rationale for the selection of Syrian hamster as animal models in biomedical research. The challenges of using Syrian hamster as an alternative animal model for the research of infectious diseases are also addressed.",2019 Oct 1,"['Miao, Jinxin', 'Chard, Louisa S.', 'Wang, Zhimin', 'Wang, Yaohe']",Front Immunol,,,True
2835b0f9f06e3e829cfa7d3f1e3805af94249d65,PMC,Oral Immunization of Chickens With Recombinant Lactobacillus plantarum Vaccine Against Early ALV-J Infection,http://dx.doi.org/10.3389/fimmu.2019.02299,PMC6783503,31632395,CC BY,"In this study, a novel oral vaccine of recombinant Lactobacillus plantarum (L. plantarum) containing the gp85 protein was explored, and the effects of this vaccine on the prevention of subgroup J Avian Leukosis Virus (ALV-J) infection were assessed. In the current study, the gp85 protein of ALV-J was expressed on the surface of L. plantarum with the surface-display motif, pgsA, by constructing a shuttle vector pMG36e:pgsA:gp85. Surface localization of the fusion protein was verified by western blotting and flow cytometry. Subsequently, Specific Pathogen Free Hy-Line Brown layer chickens were orally vaccinated with the recombinant L. plantarum and presented with high levels of serum immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA) titers in bile and duodenal-mucosal fluid. After challenged with ALV-J of a 3 × 10(3) 50% tissue culture infective dose (TCID50), serum samples of the chickens were collected and viremia was analyzed. Results showed that, compared to the L. plantarum and PBS control group, the recombinant L. plantarum group showed a significant rise in antibody levels after inoculation, and provide improved protection against ALV-J according to viremia detection. These results indicate that oral immunization with the recombinant L. plantarum provided an effective means for eliciting protective immune response against early ALV-J infection.",2019 Oct 2,"['Wang, Shenghua', 'Geng, Na', 'Zhou, Dong', 'Qu, Yi', 'Shi, Mengke', 'Xu, Yuliang', 'Liu, Kangping', 'Liu, Yongxia', 'Liu, Jianzhu']",Front Immunol,,,True
821adc5f0139622999cf4d6a2f622b51b15a07bc,PMC,First Isolation and Rapid Identification of Newcastle Disease Virus from Aborted Fetus of Dromedary Camel Using Next-Generation Sequencing,http://dx.doi.org/10.3390/v11090810,PMC6783818,31480604,CC BY,"Newcastle disease virus (NDV) causes morbidities and mortalities in wild and domestic birds globally. For humans, exposure to infected birds can cause conjunctivitis and influenza-like symptoms. NDV infections in mammals are rarely reported. In this study, using next-generation sequencing, an NDV was identified and isolated from Vero cells inoculated with the nasal swab of an aborted dromedary fetus in Dubai, during the time when an NDV outbreak occurred in a pigeon farm located in close proximity to the dairy camel farm where the mother of the aborted dromedary fetus resided, and there were a lot of pigeons in the camel farm. Genome analysis revealed that the structurally and functionally important features of other NDVs were also present in this dromedary NDV genome. Phylogenetic analysis based on the nucleotide sequences of fusion protein (F), hemagglutinin-neuraminidase protein (HN) and complete polyprotein showed that the virus belonged to sub-genotype VIg of class II NDV and is most closely related to pigeon NDVs in Egypt in the same year. The present study is the first that demonstrated isolation of NDV in dromedaries. Further study is warranted to investigate the relationship between NDV infection and abortion.",2019 Sep 1,"['Teng, Jade Lee Lee', 'Wernery, Ulrich', 'Lee, Hwei Huih', 'Joseph, Sunitha', 'Fung, Joshua', 'Elizabeth, Shyna Korah', 'Yeong, Kai Yan', 'Kinne, Joerg', 'Chan, Kwok-Hung', 'Lau, Susanna Kar Pui', 'Woo, Patrick Chiu Yat']",Viruses,,,True
9929eccac234fdba1b0c1eb46f7923c87bc9f612,PMC,First Isolation and Rapid Identification of Newcastle Disease Virus from Aborted Fetus of Dromedary Camel Using Next-Generation Sequencing,http://dx.doi.org/10.3390/v11090810,PMC6783818,31480604,CC BY,"Newcastle disease virus (NDV) causes morbidities and mortalities in wild and domestic birds globally. For humans, exposure to infected birds can cause conjunctivitis and influenza-like symptoms. NDV infections in mammals are rarely reported. In this study, using next-generation sequencing, an NDV was identified and isolated from Vero cells inoculated with the nasal swab of an aborted dromedary fetus in Dubai, during the time when an NDV outbreak occurred in a pigeon farm located in close proximity to the dairy camel farm where the mother of the aborted dromedary fetus resided, and there were a lot of pigeons in the camel farm. Genome analysis revealed that the structurally and functionally important features of other NDVs were also present in this dromedary NDV genome. Phylogenetic analysis based on the nucleotide sequences of fusion protein (F), hemagglutinin-neuraminidase protein (HN) and complete polyprotein showed that the virus belonged to sub-genotype VIg of class II NDV and is most closely related to pigeon NDVs in Egypt in the same year. The present study is the first that demonstrated isolation of NDV in dromedaries. Further study is warranted to investigate the relationship between NDV infection and abortion.",2019 Sep 1,"['Teng, Jade Lee Lee', 'Wernery, Ulrich', 'Lee, Hwei Huih', 'Joseph, Sunitha', 'Fung, Joshua', 'Elizabeth, Shyna Korah', 'Yeong, Kai Yan', 'Kinne, Joerg', 'Chan, Kwok-Hung', 'Lau, Susanna Kar Pui', 'Woo, Patrick Chiu Yat']",Viruses,,,False
eb5cf729cc61df11fa28230ff5f15bc1ec559bc5,PMC,Evolution and Genetic Diversity of Porcine Circovirus 3 in China,http://dx.doi.org/10.3390/v11090786,PMC6783837,31461875,CC BY,"The identification of a new circovirus (Porcine Circovirus 3, PCV3) has raised concern because its impact on swine health is not fully known. In Fujian Province in eastern China, even its circulating status and genetic characteristics are unclear. Here, we tested 127 tissue samples from swine from Fujian Province that presented respiratory symptoms. All of the PCV3 positive samples were negative for many other pathogens involved in respiratory diseases like PCV2, PRRSV, and CSFV, suggesting that PCV3 is potentially pathogenic. From phylogenetic analysis, PCV3 strains are divided into two main clades and five sub-clades; PCV3a-1, PCV3a-2, PCV3a-3, PCV3b-1, and PCV3b-2. Our identified strains belong to genotypes PCV3a-1, PCV3a-2, PCV3a-3, and PCV3b-2, indicating a high degree of genetic diversity of PCV3 in Fujian province until 2019. Interestingly, we found the time of the most recent common ancestor (tMRCA) of PCV3 was dated to the 1950s, and PCV3 has a similar evolutionary rate as PCV2 (the main epidemic genotypes PCV2b and PCV2d). In addition, positive selection sites N56D/S and S77T/N on the capsid gene are located on the PCV3 antigen epitope, indicating that PCV3 is gradually adaptive in swine. In summary, our results provide important insights into the epidemiology of PCV3.",2019 Aug 27,"['Chen, Ye', 'Xu, Quanming', 'Chen, Hong', 'Luo, Xian', 'Wu, Qi', 'Tan, Chen', 'Pan, Qidong', 'Chen, Ji-Long']",Viruses,,,True
e1e619d488e5bde5fce5b538540333b0a9a69718,PMC,Evolution and Genetic Diversity of Porcine Circovirus 3 in China,http://dx.doi.org/10.3390/v11090786,PMC6783837,31461875,CC BY,"The identification of a new circovirus (Porcine Circovirus 3, PCV3) has raised concern because its impact on swine health is not fully known. In Fujian Province in eastern China, even its circulating status and genetic characteristics are unclear. Here, we tested 127 tissue samples from swine from Fujian Province that presented respiratory symptoms. All of the PCV3 positive samples were negative for many other pathogens involved in respiratory diseases like PCV2, PRRSV, and CSFV, suggesting that PCV3 is potentially pathogenic. From phylogenetic analysis, PCV3 strains are divided into two main clades and five sub-clades; PCV3a-1, PCV3a-2, PCV3a-3, PCV3b-1, and PCV3b-2. Our identified strains belong to genotypes PCV3a-1, PCV3a-2, PCV3a-3, and PCV3b-2, indicating a high degree of genetic diversity of PCV3 in Fujian province until 2019. Interestingly, we found the time of the most recent common ancestor (tMRCA) of PCV3 was dated to the 1950s, and PCV3 has a similar evolutionary rate as PCV2 (the main epidemic genotypes PCV2b and PCV2d). In addition, positive selection sites N56D/S and S77T/N on the capsid gene are located on the PCV3 antigen epitope, indicating that PCV3 is gradually adaptive in swine. In summary, our results provide important insights into the epidemiology of PCV3.",2019 Aug 27,"['Chen, Ye', 'Xu, Quanming', 'Chen, Hong', 'Luo, Xian', 'Wu, Qi', 'Tan, Chen', 'Pan, Qidong', 'Chen, Ji-Long']",Viruses,,,True
9e0828fc0cba2f4c01abe363c059bb7c0036176d,PMC,Interaction of a Densovirus with Glycans of the Peritrophic Matrix Mediates Oral Infection of the Lepidopteran Pest Spodoptera frugiperda,http://dx.doi.org/10.3390/v11090870,PMC6783882,31533310,CC BY,"The success of oral infection by viruses depends on their capacity to overcome the gut epithelial barrier of their host to crossing over apical, mucous extracellular matrices. As orally transmitted viruses, densoviruses, are also challenged by the complexity of the insect gut barriers, more specifically by the chitinous peritrophic matrix, that lines and protects the midgut epithelium; how capsids stick to and cross these barriers to reach their final cell destination where replication goes has been poorly studied in insects. Here, we analyzed the early interaction of the Junonia coenia densovirus (JcDV) with the midgut barriers of caterpillars from the pest Spodoptera frugiperda. Using combination of imaging, biochemical, proteomic and transcriptomic analyses, we examined in vitro, ex vivo and in vivo the early interaction of the capsids with the peritrophic matrix and the consequence of early oral infection on the overall gut function. We show that the JcDV particle rapidly adheres to the peritrophic matrix through interaction with different glycans including chitin and glycoproteins, and that these interactions are necessary for oral infection. Proteomic analyses of JcDV binding proteins of the peritrophic matrix revealed mucins and non-mucins proteins including enzymes already known to act as receptors for several insect pathogens. In addition, we show that JcDV early infection results in an arrest of N-Acetylglucosamine secretion and a disruption in the integrity of the peritrophic matrix, which may help viral particles to pass through. Finally, JcDV early infection induces changes in midgut genes expression favoring an increased metabolism including an increased translational activity. These dysregulations probably participate to the overall dysfunction of the gut barrier in the early steps of viral pathogenesis. A better understanding of early steps of densovirus infection process is crucial to build biocontrol strategies against major insect pests.",2019 Sep 17,"['Pigeyre, Laetitia', 'Schatz, Malvina', 'Ravallec, Marc', 'Gasmi, Leila', 'Nègre, Nicolas', 'Clouet, Cécile', 'Seveno, Martial', 'El Koulali, Khadija', 'Decourcelle, Mathilde', 'Guerardel, Yann', 'Cot, Didier', 'Dupressoir, Thierry', 'Gosselin-Grenet, Anne-Sophie', 'Ogliastro, Mylène']",Viruses,,,True
4b4ac4cf566b08058a36a9ed00b7fb66f1623ae3,PMC,Selection and Characterization of Monoclonal Antibodies Targeting Middle East Respiratory Syndrome Coronavirus through a Human Synthetic Fab Phage Display Library Panning,http://dx.doi.org/10.3390/antib8030042,PMC6783954,31544848,CC BY,"Since its first report in the Middle East in 2012, the Middle East respiratory syndrome-coronavirus (MERS-CoV) has become a global concern due to the high morbidity and mortality of individuals infected with the virus. Although the majority of MERS-CoV cases have been reported in Saudi Arabia, the overall risk in areas outside the Middle East remains significant as inside Saudi Arabia. Additional pandemics of MERS-CoV are expected, and thus novel tools and reagents for therapy and diagnosis are urgently needed. Here, we used phage display to develop novel monoclonal antibodies (mAbs) that target MERS-CoV. A human Fab phage display library was panned against the S2 subunit of the MERS-CoV spike protein (MERS-S2P), yielding three unique Fabs (S2A3, S2A6, and S2D5). The Fabs had moderate apparent affinities (Half maximal effective concentration (EC(50) = 123–421 nM) for MERS-S2P, showed no cross-reactivity to spike proteins from other CoVs, and were non-aggregating and thermostable (T(m) = 61.5–80.4 °C). Reformatting the Fabs into IgGs (Immunoglobulin Gs) greatly increased their apparent affinities (K(D) = 0.17–1.2 nM), presumably due to the effects of avidity. These apparent affinities were notably higher than that of a previously reported anti-MERS-CoV S2 reference mAb (K(D) = 8.7 nM). Furthermore, two of the three mAbs (S2A3 and S2D5) bound only MERS-CoV (Erasmus Medical Center (EMC)) and not other CoVs, reflecting their high binding specificity. However, the mAbs lacked MERS-CoV neutralizing activity. Given their high affinity, specificity, and desirable stabilities, we anticipate that these anti-MERS-CoV mAbs would be suitable reagents for developing antibody-based diagnostics in laboratory or hospital settings for point-of-care testing.",2019 Jul 31,"['Kim, Yoonji', 'Lee, Hansaem', 'Park, Keunwan', 'Park, Sora', 'Lim, Ju-Hyeon', 'So, Min Kyung', 'Woo, Hye-Min', 'Ko, Hyemin', 'Lee, Jeong-Min', 'Lim, Sun Hee', 'Ko, Byoung Joon', 'Park, Yeon-Su', 'Choi, So-Young', 'Song, Du Hyun', 'Lee, Joo-Yeon', 'Kim, Sung Soon', 'Kim, Dae Young']",Antibodies (Basel),,,True
f779584a7b398e7e60721ce5cfe96fd2d0058a6b,PMC,Selection and Characterization of Monoclonal Antibodies Targeting Middle East Respiratory Syndrome Coronavirus through a Human Synthetic Fab Phage Display Library Panning,http://dx.doi.org/10.3390/antib8030042,PMC6783954,31544848,CC BY,"Since its first report in the Middle East in 2012, the Middle East respiratory syndrome-coronavirus (MERS-CoV) has become a global concern due to the high morbidity and mortality of individuals infected with the virus. Although the majority of MERS-CoV cases have been reported in Saudi Arabia, the overall risk in areas outside the Middle East remains significant as inside Saudi Arabia. Additional pandemics of MERS-CoV are expected, and thus novel tools and reagents for therapy and diagnosis are urgently needed. Here, we used phage display to develop novel monoclonal antibodies (mAbs) that target MERS-CoV. A human Fab phage display library was panned against the S2 subunit of the MERS-CoV spike protein (MERS-S2P), yielding three unique Fabs (S2A3, S2A6, and S2D5). The Fabs had moderate apparent affinities (Half maximal effective concentration (EC(50) = 123–421 nM) for MERS-S2P, showed no cross-reactivity to spike proteins from other CoVs, and were non-aggregating and thermostable (T(m) = 61.5–80.4 °C). Reformatting the Fabs into IgGs (Immunoglobulin Gs) greatly increased their apparent affinities (K(D) = 0.17–1.2 nM), presumably due to the effects of avidity. These apparent affinities were notably higher than that of a previously reported anti-MERS-CoV S2 reference mAb (K(D) = 8.7 nM). Furthermore, two of the three mAbs (S2A3 and S2D5) bound only MERS-CoV (Erasmus Medical Center (EMC)) and not other CoVs, reflecting their high binding specificity. However, the mAbs lacked MERS-CoV neutralizing activity. Given their high affinity, specificity, and desirable stabilities, we anticipate that these anti-MERS-CoV mAbs would be suitable reagents for developing antibody-based diagnostics in laboratory or hospital settings for point-of-care testing.",2019 Jul 31,"['Kim, Yoonji', 'Lee, Hansaem', 'Park, Keunwan', 'Park, Sora', 'Lim, Ju-Hyeon', 'So, Min Kyung', 'Woo, Hye-Min', 'Ko, Hyemin', 'Lee, Jeong-Min', 'Lim, Sun Hee', 'Ko, Byoung Joon', 'Park, Yeon-Su', 'Choi, So-Young', 'Song, Du Hyun', 'Lee, Joo-Yeon', 'Kim, Sung Soon', 'Kim, Dae Young']",Antibodies (Basel),,,False
f2d560b5f6bd9fcad15c0b5e6e4284cfe9386e3c,PMC,Long-Acting HIV-1 Fusion Inhibitory Peptides and their Mechanisms of Action,http://dx.doi.org/10.3390/v11090811,PMC6784077,31480738,CC BY,"The clinical application of HIV fusion inhibitor, enfuvirtide (T20), was limited mainly because of its short half-life. Here we designed and synthesized two PEGylated C34 peptides, PEG2kC34 and PEG5kC34, with the PEG chain length of 2 and 5 kDa, respectively, and evaluated their anti-HIV-1 activity and mechanisms of action. We found that these two PEGylated peptides could bind to the HIV-1 peptide N36 to form high affinity complexes with high α-helicity. The peptides PEG2kC34 and PEG5kC34 effectively inhibited HIV-1 Env-mediated cell–cell fusion with an effective concentration for 50% inhibition (EC(50)) of about 36 nM. They also inhibited infection of the laboratory-adapted HIV-1 strain NL4-3 with EC(50) of about 4–5 nM, and against 47 HIV-1 clinical isolates circulating in China with mean EC(50) of PEG2kC34 and PEG5kC34 of about 26 nM and 32 nM, respectively. The plasma half-life (t(1/2)) of PEG2kC34 and PEG5kC34 was 2.6 h and 5.1 h, respectively, and the t(1/2) of PEGylated C34 was about 2.4-fold and 4.6-fold longer than C34 (~1.1 h), respectively. These findings suggest that PEGylated C34 with broad-spectrum anti-HIV-1 activity and prolonged half-life can be further developed as a peptide fusion inhibitor-based long-acting anti-HIV drug for clinical use to treat HIV-infected patients who have failed to respond to current anti-retrovirus drugs.",2019 Sep 2,"['Wang, Chen', 'Cheng, Shuihong', 'Zhang, Yuanyuan', 'Ding, Yibo', 'Chong, Huihui', 'Xing, Hui', 'Jiang, Shibo', 'Li, Xuebing', 'Ma, Liying']",Viruses,,,True
5bbf8689ab8b16eeb47592fc469a390f63fa232e,PMC,A Methodology for Determining Which Diseases Warrant Care in a High-Level Containment Care Unit †,http://dx.doi.org/10.3390/v11090773,PMC6784089,31443440,CC BY,"Although the concept of high-level containment care (HLCC or ‘biocontainment’), dates back to 1969, the 2014–2016 outbreak of Ebola virus disease (EVD) brought with it a renewed emphasis on the use of specialized HLCC units in the care of patients with EVD. Employment of these units in the United States and Western Europe resulted in a significant decrease in mortality compared to traditional management in field settings. Moreover, this employment appeared to significantly lessen the risk of nosocomial transmission of disease; no secondary cases occurred among healthcare workers in these units. While many now accept the wisdom of utilizing HLCC units and principles in the management of EVD (and, presumably, of other transmissible and highly hazardous viral hemorrhagic fevers, such as those caused by Marburg and Lassa viruses), no consensus exists regarding additional diseases that might warrant HLCC. We propose here a construct designed to make such determinations for existing and newly discovered diseases. The construct examines infectivity (as measured by the infectious dose needed to infect 50% of a given population (ID(50))), communicability (as measured by the reproductive number (R(0))), and hazard (as measured by morbidity and mortality). Diseases fulfilling all three criteria (i.e., those that are highly infectious, communicable, and highly hazardous) are considered candidates for HLCC management if they also meet a fourth criterion, namely that they lack effective and available licensed countermeasures.",2019 Aug 22,"['Cieslak, Theodore J.', 'Herstein, Jocelyn J.', 'Kortepeter, Mark G.', 'Hewlett, Angela L.']",Viruses,,,True
89fc23ed55ad474b4b4056c0a3dadd315573f57e,PMC,A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice,http://dx.doi.org/10.3390/v11090799,PMC6784119,31470645,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV), a new coronavirus that has been causing severe and fatal acute respiratory illnesses in humans since its outbreak in 2012, has raised public fear worldwide. The development of prophylactics and therapeutics is urgently needed to prevent and control MERS-CoV infections. In this study, a bacterium (Lactococcus lactis)-like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). The designs included different numbers of lysin motif (LysM) repeats in the PAs linked by linkers (RBD-linker-PA2 (RLP(2)), RBD-linker-PA3 (RLP(3)) and RBD-PA3 (RP(3))), and three LysM repeats and a linker in the fusion proteins increased the binding activity to the RBD. The specific immune responses were tested by intranasally immunizing mice with RLP(3)-GEM with or without the adjuvant GEL01. The results showed that GEL01-adjuvanted RLP(3)-GEM increased the systemic humoral, cellular and local mucosal immune responses in the mouse model, especially in the intestinal tract. The above results indicate that the MERS-CoV BLP product has the potential to be developed into a promising mucosal candidate vaccine to protect against MERS-CoV infections.",2019 Aug 29,"['Li, Entao', 'Chi, Hang', 'Huang, Pei', 'Yan, Feihu', 'Zhang, Ying', 'Liu, Chuanyu', 'Wang, Zhenshan', 'Li, Guohua', 'Zhang, Shengnan', 'Mo, Ruo', 'Jin, Hongli', 'Wang, Hualei', 'Feng, Na', 'Wang, Jianzhong', 'Bi, Yuhai', 'Wang, Tiecheng', 'Sun, Weiyang', 'Gao, Yuwei', 'Zhao, Yongkun', 'Yang, Songtao', 'Xia, Xianzhu']",Viruses,,,True
c0bf3eba76bbd23ffe7c259b7de7f7c66886f22c,PMC,Fusogenicity of the Ghana Virus (Henipavirus: Ghanaian bat henipavirus) Fusion Protein is Controlled by the Cytoplasmic Domain of the Attachment Glycoprotein,http://dx.doi.org/10.3390/v11090800,PMC6784138,31470664,CC BY,"The Ghana virus (GhV) is phylogenetically related to the zoonotic henipaviruses Nipah (NiV) and Hendra virus. Although GhV uses the highly conserved receptor ephrin-B2, the fusogenicity is restricted to cell lines of bat origin. Furthermore, the surface expression of the GhV attachment glycoprotein (G) is reduced compared to NiV and most of this protein is retained in the endoplasmic reticulum (ER). Here, we generated truncated as well as chimeric GhV G proteins and investigated the influence of the structural domains (cytoplasmic tail, transmembrane domain, ectodomain) of this protein on the intracellular transport and the fusogenicity following coexpression with the GhV fusion protein (F). We demonstrate that neither the cytoplasmic tail nor the transmembrane domain is responsible for the intracellular retention of GhV G. Furthermore, the cytoplasmic tail of GhV G modulates the fusogenicity of GhV F and therefore controls the species-restricted fusogenicity of the GhV surface glycoproteins.",2019 Aug 29,"['Voigt, Kathleen', 'Hoffmann, Markus', 'Drexler, Jan Felix', 'Müller, Marcel Alexander', 'Drosten, Christian', 'Herrler, Georg', 'Krüger, Nadine']",Viruses,,,True
22a7db49b1d6a2856d8737d3739af18b715cd399,PMC,"Recombination in Enteroviruses, a Multi-Step Modular Evolutionary Process",http://dx.doi.org/10.3390/v11090859,PMC6784155,31540135,CC BY,"RNA recombination is a major driving force in the evolution and genetic architecture shaping of enteroviruses. In particular, intertypic recombination is implicated in the emergence of most pathogenic circulating vaccine-derived polioviruses, which have caused numerous outbreaks of paralytic poliomyelitis worldwide. Recent experimental studies that relied on recombination cellular systems mimicking natural genetic exchanges between enteroviruses provided new insights into the molecular mechanisms of enterovirus recombination and enabled to define a new model of genetic plasticity for enteroviruses. Homologous intertypic recombinant enteroviruses that were observed in nature would be the final products of a multi-step process, during which precursor nonhomologous recombinant genomes are generated through an initial inter-genomic RNA recombination event and can then evolve into a diversity of fitter homologous recombinant genomes over subsequent intra-genomic rearrangements. Moreover, these experimental studies demonstrated that the enterovirus genome could be defined as a combination of genomic modules that can be preferentially exchanged through recombination, and enabled defining the boundaries of these recombination modules. These results provided the first experimental evidence supporting the theoretical model of enterovirus modular evolution previously elaborated from phylogenetic studies of circulating enterovirus strains. This review summarizes our current knowledge regarding the mechanisms of recombination in enteroviruses and presents a new evolutionary process that may apply to other RNA viruses.",2019 Sep 14,"['Muslin, Claire', 'Mac Kain, Alice', 'Bessaud, Maël', 'Blondel, Bruno', 'Delpeyroux, Francis']",Viruses,,,True
9ce30445b5bd0de8a1b013393e53d17aa8bcb409,PMC,Pulmonary Involvement during the Ebola Virus Disease,http://dx.doi.org/10.3390/v11090780,PMC6784166,31450596,CC BY,"Filoviruses have become a worldwide public health concern, especially during the 2013–2016 Western Africa Ebola virus disease (EVD) outbreak—the largest outbreak, both by number of cases and geographical extension, recorded so far in medical history. EVD is associated with pathologies in several organs, including the liver, kidney, and lung. During the 2013–2016 Western Africa outbreak, Ebola virus (EBOV) was detected in the lung of infected patients suggesting a role in lung pathogenesis. However, little is known about lung pathogenesis and the controversial issue of aerosol transmission in EVD. This review highlights the pulmonary involvement in EVD, with a special focus on the new data emerging from the 2013–2016 Ebola outbreak.",2019 Aug 24,"['Lalle, Eleonora', 'Biava, Mirella', 'Nicastri, Emanuele', 'Colavita, Francesca', 'Di Caro, Antonino', 'Vairo, Francesco', 'Lanini, Simone', 'Castilletti, Concetta', 'Langer, Martin', 'Zumla, Alimuddin', 'Kobinger, Gary', 'Capobianchi, Maria R.', 'Ippolito, Giuseppe']",Viruses,,,True
4bf70dfd0cd0819f2eb424d977abedc85f5444d1,PMC,A Fusion Peptide in the Spike Protein of MERS Coronavirus,http://dx.doi.org/10.3390/v11090825,PMC6784214,31491938,CC BY,"Coronaviruses represent current and emerging threats for many species, including humans. Middle East respiratory syndrome-related coronavirus (MERS-CoV) is responsible for sporadic infections in mostly Middle Eastern countries, with occasional transfer elsewhere. A key step in the MERS-CoV replication cycle is the fusion of the virus and host cell membranes mediated by the virus spike protein, S. The location of the fusion peptide within the MERS S protein has not been precisely mapped. We used isolated peptides and giant unilamellar vesicles (GUV) to demonstrate membrane binding for a peptide located near the N-terminus of the S2 domain. Key residues required for activity were mapped by amino acid replacement and their relevance in vitro tested by their introduction into recombinant MERS S protein expressed in mammalian cells. Mutations preventing membrane binding in vitro also abolished S-mediated syncytium formation consistent with the identified peptide acting as the fusion peptide for the S protein of MERS-CoV.",2019 Sep 5,"['Alsaadi, Entedar A. J.', 'Neuman, Benjamin W.', 'Jones, Ian M.']",Viruses,,,True
c4a909da9b4ab2d9a0a9f4305e1cdc4bc66f9d03,PMC,Discovery and Characterization of Novel RNA Viruses in Aquatic North American Wild Birds,http://dx.doi.org/10.3390/v11090768,PMC6784231,31438486,CC BY,"Wild birds are recognized viral reservoirs but our understanding about avian viral diversity is limited. We describe here three novel RNA viruses that we identified in oropharyngeal/cloacal swabs collected from wild birds. The complete genome of a novel gull metapneumovirus (GuMPV B29) was determined. Phylogenetic analyses indicated that this virus could represent a novel avian metapneumovirus (AMPV) sub-group, intermediate between AMPV-C and the subgroup of the other AMPVs. This virus was detected in an American herring (1/24, 4.2%) and great black-backed (4/26, 15.4%) gulls. A novel gull coronavirus (GuCoV B29) was detected in great black-backed (3/26, 11.5%) and American herring (2/24, 8.3%) gulls. Phylogenetic analyses of GuCoV B29 suggested that this virus could represent a novel species within the genus Gammacoronavirus, close to other recently identified potential novel avian coronaviral species. One GuMPV–GuCoV co-infection was detected. A novel duck calicivirus (DuCV-2 B6) was identified in mallards (2/5, 40%) and American black ducks (7/26, 26.9%). This virus, of which we identified two different types, was fully sequenced and was genetically closest to other caliciviruses identified in Anatidae, but more distant to other caliciviruses from birds in the genus Anas. These discoveries increase our knowledge about avian virus diversity and host distributions.",2019 Aug 21,"['Canuti, Marta', 'Kroyer, Ashley N. K.', 'Ojkic, Davor', 'Whitney, Hugh G.', 'Robertson, Gregory J.', 'Lang, Andrew S.']",Viruses,,,True
9cdd0959f4a3ba21a9d0b4c5e8707780f5c464ef,PMC,Discovery and Characterization of Novel RNA Viruses in Aquatic North American Wild Birds,http://dx.doi.org/10.3390/v11090768,PMC6784231,31438486,CC BY,"Wild birds are recognized viral reservoirs but our understanding about avian viral diversity is limited. We describe here three novel RNA viruses that we identified in oropharyngeal/cloacal swabs collected from wild birds. The complete genome of a novel gull metapneumovirus (GuMPV B29) was determined. Phylogenetic analyses indicated that this virus could represent a novel avian metapneumovirus (AMPV) sub-group, intermediate between AMPV-C and the subgroup of the other AMPVs. This virus was detected in an American herring (1/24, 4.2%) and great black-backed (4/26, 15.4%) gulls. A novel gull coronavirus (GuCoV B29) was detected in great black-backed (3/26, 11.5%) and American herring (2/24, 8.3%) gulls. Phylogenetic analyses of GuCoV B29 suggested that this virus could represent a novel species within the genus Gammacoronavirus, close to other recently identified potential novel avian coronaviral species. One GuMPV–GuCoV co-infection was detected. A novel duck calicivirus (DuCV-2 B6) was identified in mallards (2/5, 40%) and American black ducks (7/26, 26.9%). This virus, of which we identified two different types, was fully sequenced and was genetically closest to other caliciviruses identified in Anatidae, but more distant to other caliciviruses from birds in the genus Anas. These discoveries increase our knowledge about avian virus diversity and host distributions.",2019 Aug 21,"['Canuti, Marta', 'Kroyer, Ashley N. K.', 'Ojkic, Davor', 'Whitney, Hugh G.', 'Robertson, Gregory J.', 'Lang, Andrew S.']",Viruses,,,True
dcbe31a68ac67d38ccdae0615ebabd8461bd7095,PMC,"To Go or Stay: The Development, Benefit, and Detriment of Tissue-Resident Memory CD8 T Cells during Central Nervous System Viral Infections",http://dx.doi.org/10.3390/v11090842,PMC6784233,31514273,CC BY,"CD8 T cells coordinate immune defenses against viral infections of the central nervous system (CNS). Virus-specific CD8 T cells infiltrate the CNS and differentiate into brain-resident memory CD8 T cells (CD8 bT(RM)). CD8 bT(RM) are characterized by a lack of recirculation and expression of phenotypes and transcriptomes distinct from other CD8 T cell memory subsets. CD8 bT(RM) have been shown to provide durable, autonomous protection against viral reinfection and the resurgence of latent viral infections. CD8 T cells have also been implicated in the development of neural damage following viral infection, which demonstrates that the infiltration of CD8 T cells into the brain can also be pathogenic. In this review, we will explore the residency and maintenance requirements for CD8 bT(RM) and discuss their roles in controlling viral infections of the brain.",2019 Sep 11,"['Mockus, Taryn E.', 'Ren, Heather M.', 'Shwetank,', 'Lukacher, Aron E.']",Viruses,,,True
f7453f0f1f131d4f8603bf708f8c08d9b9e8806f,PMC,The Proteolytic Regulation of Virus Cell Entry by Furin and Other Proprotein Convertases,http://dx.doi.org/10.3390/v11090837,PMC6784293,31505793,CC BY,"A wide variety of viruses exploit furin and other proprotein convertases (PCs) of the constitutive protein secretion pathway in order to regulate their cell entry mechanism and infectivity. Surface proteins of enveloped, as well as non-enveloped, viruses become processed by these proteases intracellularly during morphogenesis or extracellularly after egress and during entry in order to produce mature virions activated for infection. Although viruses also take advantage of other proteases, it is when some viruses become reactive with PCs that they may develop high pathogenicity. Besides reacting with furin, some viruses may also react with the PCs of the other specificity group constituted by PC4/PC5/PACE4/PC7. The targeting of PCs for inhibition may result in a useful strategy to treat infections with some highly pathogenic viruses. A wide variety of PC inhibitors have been developed and tested for their antiviral activity in cell-based assays.",2019 Sep 9,"Izaguirre, Gonzalo",Viruses,,,True
db5d43606d70dcc0d0c32778aed4611d699b909d,PMC,Tick-borne encephalitis virus inhibits rRNA synthesis and host protein production in human cells of neural origin,http://dx.doi.org/10.1371/journal.pntd.0007745,PMC6785130,31560682,CC BY,"Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus (Flaviviridae), is a causative agent of a severe neuroinfection. Recently, several flaviviruses have been shown to interact with host protein synthesis. In order to determine whether TBEV interacts with this host process in its natural target cells, we analysed de novo protein synthesis in a human cell line derived from cerebellar medulloblastoma (DAOY HTB-186). We observed a significant decrease in the rate of host protein synthesis, including the housekeeping genes HPRT1 and GAPDH and the known interferon-stimulated gene viperin. In addition, TBEV infection resulted in a specific decrease of RNA polymerase I (POLR1) transcripts, 18S and 28S rRNAs and their precursor, 45-47S pre-rRNA, but had no effect on the POLR3 transcribed 5S rRNA levels. To our knowledge, this is the first report of flavivirus-induced decrease of specifically POLR1 rRNA transcripts accompanied by host translational shut-off.",2019 Sep 27,"['Selinger, Martin', 'Tykalová, Hana', 'Štěrba, Ján', 'Věchtová, Pavlína', 'Vavrušková, Zuzana', 'Lieskovská, Jaroslava', 'Kohl, Alain', 'Schnettler, Esther', 'Grubhoffer, Libor']",PLoS Negl Trop Dis,,,True
4e34e10d336bfc70e73855fd7714534f78595ebe,PMC,Tick-borne encephalitis virus inhibits rRNA synthesis and host protein production in human cells of neural origin,http://dx.doi.org/10.1371/journal.pntd.0007745,PMC6785130,31560682,CC BY,"Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus (Flaviviridae), is a causative agent of a severe neuroinfection. Recently, several flaviviruses have been shown to interact with host protein synthesis. In order to determine whether TBEV interacts with this host process in its natural target cells, we analysed de novo protein synthesis in a human cell line derived from cerebellar medulloblastoma (DAOY HTB-186). We observed a significant decrease in the rate of host protein synthesis, including the housekeeping genes HPRT1 and GAPDH and the known interferon-stimulated gene viperin. In addition, TBEV infection resulted in a specific decrease of RNA polymerase I (POLR1) transcripts, 18S and 28S rRNAs and their precursor, 45-47S pre-rRNA, but had no effect on the POLR3 transcribed 5S rRNA levels. To our knowledge, this is the first report of flavivirus-induced decrease of specifically POLR1 rRNA transcripts accompanied by host translational shut-off.",2019 Sep 27,"['Selinger, Martin', 'Tykalová, Hana', 'Štěrba, Ján', 'Věchtová, Pavlína', 'Vavrušková, Zuzana', 'Lieskovská, Jaroslava', 'Kohl, Alain', 'Schnettler, Esther', 'Grubhoffer, Libor']",PLoS Negl Trop Dis,,,False
aefd3e6661ed4befc6dd11d15cb80a66e025102e,PMC,"Prevalence, clinical outcomes and rainfall association of acute respiratory infection by human metapneumovirus in children in Bogotá, Colombia",http://dx.doi.org/10.1186/s12887-019-1734-x,PMC6785857,31601181,CC BY,"BACKGROUND: Acute respiratory infections (ARIs) are one of the main causes of morbidity and mortality in children. Viruses are the main etiological agents, and their behavior tends to be seasonal and vary by geographical location. Human metapneumovirus (HMPV) has recently been described as a cause of severe acute respiratory infection and its prevalence and clinical behavior in children at moderate altitudes is unknown. METHODS: A cross-sectional study was carried out on patients seen at a university hospital in Bogotá, Colombia between October 2015 and December 2017 in a city at a moderate altitude above sea level. Children with acute respiratory infections who had had a multiplex RT-PCR assay were selected. The prevalence of HMPV infection, its clinical outcomes and its relationship to rainfall were evaluated. RESULTS: Out of a total of 14,760 discharged patients, multiplex RT-PCR was performed on 502 and a virus was detected in 420 children with acute respiratory infection (ARI). The study group had a median age of 21 months (IQR 7–60), with similar proportion of males and females (56.4 and 43.6% respectively) and 5.2% (CI 95 3.3–7.8%) prevalence of HMPV infection. The group with HMPV infection showed a greater frequency of viral coinfection (22.7% vs 14% P = 0.03) compared with ARI caused by other viruses. The rate of bacterial coinfection (P = 0.31), presence of comorbidities (p = 0.75), length of hospital stay (P = 0.42), need for mechanical ventilation (P = 0.75) and mortality (P = 0.22) were similar for HMPV and other viral infections. A moderate correlation was established between HMPV infection and rainfall peaks (Spearman’s Rho 0.44 p = 0.02). CONCLUSIONS: Human metapneumovirus was the fifth most frequently isolated virus in children with ARI, had similar clinical behavior and severity to other viruses but a higher rate of viral coinfection. Its peaks seem to correlate to rainy seasons.",2019 Oct 10,"['Evelyn, Obando', 'Jaime, Fernández-Sarmiento', 'David, Montoya', 'Lorena, Acevedo', 'Jenifer, Arroyave', 'Oscar, Gamboa']",BMC Pediatr,,,True
71d047965ff6d3d2dc68d07cb90770fce84edcb8,PMC,Recent advances in delivery of veterinary DNA vaccines against avian pathogens,http://dx.doi.org/10.1186/s13567-019-0698-z,PMC6785882,31601266,CC BY,"Veterinary vaccines need to have desired characteristics, such as being effective, inexpensive, easy to administer, suitable for mass vaccination and stable under field conditions. DNA vaccines have been proposed as potential solutions for poultry diseases since they are subunit vaccines with no risk of infection or reversion to virulence. DNA vaccines can be utilized for simultaneous immunizations against multiple pathogens and are relatively easy to design and inexpensive to manufacture and store. Administration of DNA vaccines has been shown to stimulate immune responses and provide protection from challenges in different animal models. Although DNA vaccines offer advantages, setbacks including the inability to induce strong immunity, and the fact that they are not currently applicable for mass vaccination impede the use of DNA vaccines in the poultry industry. The use of either biological or physical carriers has been proposed as a solution to overcome the current delivery limitations of DNA vaccines for veterinary applications. This review presents an overview of the recent development of carriers for delivery of veterinary DNA vaccines against avian pathogens.",2019 Oct 10,"['Jazayeri, Seyed Davoud', 'Poh, Chit Laa']",Vet Res,,,True
8538c23b7be59b19a8376c51d6ec269c00b34bec,PMC,"Pathogen surveillance in the informal settlement, Kibera, Kenya, using a metagenomics approach",http://dx.doi.org/10.1371/journal.pone.0222531,PMC6786639,31600207,CC0,"BACKGROUND: Worldwide, the number of emerging and re-emerging infectious diseases is increasing, highlighting the importance of global disease pathogen surveillance. Traditional population-based methods may fail to capture important events, particularly in settings with limited access to health care, such as urban informal settlements. In such environments, a mixture of surface water runoff and human feces containing pathogenic microorganisms could be used as a surveillance surrogate. METHOD: We conducted a temporal metagenomic analysis of urban sewage from Kibera, an urban informal settlement in Nairobi, Kenya, to detect and quantify bacterial and associated antimicrobial resistance (AMR) determinants, viral and parasitic pathogens. Data were examined in conjunction with data from ongoing clinical infectious disease surveillance. RESULTS: A large variation of read abundances related to bacteria, viruses, and parasites of medical importance, as well as bacterial associated antimicrobial resistance genes over time were detected. Significant increased abundances were observed for a number of bacterial pathogens coinciding with higher abundances of AMR genes. Vibrio cholerae as well as rotavirus A, among other virus peaked in several weeks during the study period whereas Cryptosporidium spp. and Giardia spp, varied more over time. CONCLUSION: The metagenomic surveillance approach for monitoring circulating pathogens in sewage was able to detect putative pathogen and resistance loads in an urban informal settlement. Thus, valuable if generated in real time to serve as a comprehensive infectious disease agent surveillance system with the potential to guide disease prevention and treatment. The approach may lead to a paradigm shift in conducting real-time global genomics-based surveillance in settings with limited access to health care.",2019 Oct 10,"['Hendriksen, Rene S.', 'Lukjancenko, Oksana', 'Munk, Patrick', 'Hjelmsø, Mathis H.', 'Verani, Jennifer R.', 'Ng’eno, Eric', 'Bigogo, Godfrey', 'Kiplangat, Samuel', 'Oumar, Traoré', 'Bergmark, Lasse', 'Röder, Timo', 'Neatherlin, John C.', 'Clayton, Onyango', 'Hald, Tine', 'Karlsmose, Susanne', 'Pamp, Sünje J.', 'Fields, Barry', 'Montgomery, Joel M.', 'Aarestrup, Frank M.']",PLoS One,,,True
35dd113e67ede7d921128d82d5a0077071a8ee78,PMC,Thermodynamic control of −1 programmed ribosomal frameshifting,http://dx.doi.org/10.1038/s41467-019-12648-x,PMC6787027,31601802,CC BY,"mRNA contexts containing a ‘slippery’ sequence and a downstream secondary structure element stall the progression of the ribosome along the mRNA and induce its movement into the −1 reading frame. In this study we build a thermodynamic model based on Bayesian statistics to explain how −1 programmed ribosome frameshifting can work. As training sets for the model, we measured frameshifting efficiencies on 64 dnaX mRNA sequence variants in vitro and also used 21 published in vivo efficiencies. With the obtained free-energy difference between mRNA-tRNA base pairs in the 0 and −1 frames, the frameshifting efficiency of a given sequence can be reproduced and predicted from the tRNA−mRNA base pairing in the two frames. Our results further explain how modifications in the tRNA anticodon modulate frameshifting and show how the ribosome tunes the strength of the base-pair interactions.",2019 Oct 10,"['Bock, Lars V.', 'Caliskan, Neva', 'Korniy, Natalia', 'Peske, Frank', 'Rodnina, Marina V.', 'Grubmüller, Helmut']",Nat Commun,,,True
e6cf2b64c780ee6a1077c087d270ce896d35ede2,PMC,Thermodynamic control of −1 programmed ribosomal frameshifting,http://dx.doi.org/10.1038/s41467-019-12648-x,PMC6787027,31601802,CC BY,"mRNA contexts containing a ‘slippery’ sequence and a downstream secondary structure element stall the progression of the ribosome along the mRNA and induce its movement into the −1 reading frame. In this study we build a thermodynamic model based on Bayesian statistics to explain how −1 programmed ribosome frameshifting can work. As training sets for the model, we measured frameshifting efficiencies on 64 dnaX mRNA sequence variants in vitro and also used 21 published in vivo efficiencies. With the obtained free-energy difference between mRNA-tRNA base pairs in the 0 and −1 frames, the frameshifting efficiency of a given sequence can be reproduced and predicted from the tRNA−mRNA base pairing in the two frames. Our results further explain how modifications in the tRNA anticodon modulate frameshifting and show how the ribosome tunes the strength of the base-pair interactions.",2019 Oct 10,"['Bock, Lars V.', 'Caliskan, Neva', 'Korniy, Natalia', 'Peske, Frank', 'Rodnina, Marina V.', 'Grubmüller, Helmut']",Nat Commun,,,False
f21e37eb61b6a339d38fb7bd9a350faa23fb676c,PMC,Thermodynamic control of −1 programmed ribosomal frameshifting,http://dx.doi.org/10.1038/s41467-019-12648-x,PMC6787027,31601802,CC BY,"mRNA contexts containing a ‘slippery’ sequence and a downstream secondary structure element stall the progression of the ribosome along the mRNA and induce its movement into the −1 reading frame. In this study we build a thermodynamic model based on Bayesian statistics to explain how −1 programmed ribosome frameshifting can work. As training sets for the model, we measured frameshifting efficiencies on 64 dnaX mRNA sequence variants in vitro and also used 21 published in vivo efficiencies. With the obtained free-energy difference between mRNA-tRNA base pairs in the 0 and −1 frames, the frameshifting efficiency of a given sequence can be reproduced and predicted from the tRNA−mRNA base pairing in the two frames. Our results further explain how modifications in the tRNA anticodon modulate frameshifting and show how the ribosome tunes the strength of the base-pair interactions.",2019 Oct 10,"['Bock, Lars V.', 'Caliskan, Neva', 'Korniy, Natalia', 'Peske, Frank', 'Rodnina, Marina V.', 'Grubmüller, Helmut']",Nat Commun,,,False
c0bf910304f6b63067f1f28709b964272cd6c182,PMC,Thermodynamic control of −1 programmed ribosomal frameshifting,http://dx.doi.org/10.1038/s41467-019-12648-x,PMC6787027,31601802,CC BY,"mRNA contexts containing a ‘slippery’ sequence and a downstream secondary structure element stall the progression of the ribosome along the mRNA and induce its movement into the −1 reading frame. In this study we build a thermodynamic model based on Bayesian statistics to explain how −1 programmed ribosome frameshifting can work. As training sets for the model, we measured frameshifting efficiencies on 64 dnaX mRNA sequence variants in vitro and also used 21 published in vivo efficiencies. With the obtained free-energy difference between mRNA-tRNA base pairs in the 0 and −1 frames, the frameshifting efficiency of a given sequence can be reproduced and predicted from the tRNA−mRNA base pairing in the two frames. Our results further explain how modifications in the tRNA anticodon modulate frameshifting and show how the ribosome tunes the strength of the base-pair interactions.",2019 Oct 10,"['Bock, Lars V.', 'Caliskan, Neva', 'Korniy, Natalia', 'Peske, Frank', 'Rodnina, Marina V.', 'Grubmüller, Helmut']",Nat Commun,,,True
65ca70396d041072aeab57a007cffef0870897cf,PMC,Common Nodes of Virus–Host Interaction Revealed Through an Integrated Network Analysis,http://dx.doi.org/10.3389/fimmu.2019.02186,PMC6787150,31636628,CC BY,"Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.",2019 Oct 4,"['Bösl, Korbinian', 'Ianevski, Aleksandr', 'Than, Thoa T.', 'Andersen, Petter I.', 'Kuivanen, Suvi', 'Teppor, Mona', 'Zusinaite, Eva', 'Dumpis, Uga', 'Vitkauskiene, Astra', 'Cox, Rebecca J.', 'Kallio-Kokko, Hannimari', 'Bergqvist, Anders', 'Tenson, Tanel', 'Merits, Andres', 'Oksenych, Valentyn', 'Bjørås, Magnar', 'Anthonsen, Marit W.', 'Shum, David', 'Kaarbø, Mari', 'Vapalahti, Olli', 'Windisch, Marc P.', 'Superti-Furga, Giulio', 'Snijder, Berend', 'Kainov, Denis', 'Kandasamy, Richard K.']",Front Immunol,,,True
17e332ee9749801d74a9cf58512014289688801c,PMC,CD206(+) tumor-associated macrophages promote proliferation and invasion in oral squamous cell carcinoma via EGF production,http://dx.doi.org/10.1038/s41598-019-51149-1,PMC6787225,31601953,CC BY,"Tumor-associated macrophages (TAMs) promote tumor progression and inhibit anti-tumor immune response by producing various mediators and preferentially express CD163, CD204, and CD206. However, the role of these TAM subsets in oral squamous cell carcinoma (OSCC) remains unclear. Here we investigated the expression and function of TAM subsets in OSCC, especially in cancer cell proliferation. Biopsy sample from 44 patients with OSCC were examined for the expression of TAM markers and EGF by immunohistochemistry. EGF production of TAM subsets isolated from OSCC patients was assessed by flow cytometry. We also examined the effect of conditioned medium from TAM subsets on the proliferation of OSCC cells. CD163(+) cells were detected diffusely all over the tumor and connective tissue area, while CD204(+) and CD206(+) cells were mainly detected in/around the tumors. Flow cytometric analysis found that CD206(+) TAMs strongly produced EGF compared with CD163(+) and CD204(+) TAMs. Cell proliferation and invasion of OSCC cells cultured with conditioned medium of CD206(+) TAMs were strongly enhanced and inhibited by anti-EGFR. The number of CD206(+) TAMs positively correlated with worse clinical prognosis. Our results revealed differences in localization and EGF production among these TAM subsets. CD206(+) TAMs might play a critical role in the proliferation of OSCC via EGF production.",2019 Oct 10,"['Haque, A. S. M. Rafiul', 'Moriyama, Masafumi', 'Kubota, Keigo', 'Ishiguro, Noriko', 'Sakamoto, Mizuki', 'Chinju, Akira', 'Mochizuki, Keita', 'Sakamoto, Taiki', 'Kaneko, Naoki', 'Munemura, Ryusuke', 'Maehara, Takashi', 'Tanaka, Akihiko', 'Hayashida, Jun-Nosuke', 'Kawano, Shintaro', 'Kiyoshima, Tamotsu', 'Nakamura, Seiji']",Sci Rep,,,False
310c97d16197e1ab6ff3227b706bed41f079b8ae,PMC,CD206(+) tumor-associated macrophages promote proliferation and invasion in oral squamous cell carcinoma via EGF production,http://dx.doi.org/10.1038/s41598-019-51149-1,PMC6787225,31601953,CC BY,"Tumor-associated macrophages (TAMs) promote tumor progression and inhibit anti-tumor immune response by producing various mediators and preferentially express CD163, CD204, and CD206. However, the role of these TAM subsets in oral squamous cell carcinoma (OSCC) remains unclear. Here we investigated the expression and function of TAM subsets in OSCC, especially in cancer cell proliferation. Biopsy sample from 44 patients with OSCC were examined for the expression of TAM markers and EGF by immunohistochemistry. EGF production of TAM subsets isolated from OSCC patients was assessed by flow cytometry. We also examined the effect of conditioned medium from TAM subsets on the proliferation of OSCC cells. CD163(+) cells were detected diffusely all over the tumor and connective tissue area, while CD204(+) and CD206(+) cells were mainly detected in/around the tumors. Flow cytometric analysis found that CD206(+) TAMs strongly produced EGF compared with CD163(+) and CD204(+) TAMs. Cell proliferation and invasion of OSCC cells cultured with conditioned medium of CD206(+) TAMs were strongly enhanced and inhibited by anti-EGFR. The number of CD206(+) TAMs positively correlated with worse clinical prognosis. Our results revealed differences in localization and EGF production among these TAM subsets. CD206(+) TAMs might play a critical role in the proliferation of OSCC via EGF production.",2019 Oct 10,"['Haque, A. S. M. Rafiul', 'Moriyama, Masafumi', 'Kubota, Keigo', 'Ishiguro, Noriko', 'Sakamoto, Mizuki', 'Chinju, Akira', 'Mochizuki, Keita', 'Sakamoto, Taiki', 'Kaneko, Naoki', 'Munemura, Ryusuke', 'Maehara, Takashi', 'Tanaka, Akihiko', 'Hayashida, Jun-Nosuke', 'Kawano, Shintaro', 'Kiyoshima, Tamotsu', 'Nakamura, Seiji']",Sci Rep,,,True
8778a5efe2618f5d7c1873b4f1d6c6b49464e2c6,PMC,VCP/p97 Is a Proviral Host Factor for Replication of Chikungunya Virus and Other Alphaviruses,http://dx.doi.org/10.3389/fmicb.2019.02236,PMC6787436,31636613,CC BY,"The evolutionarily conserved AAA+ ATPase valosin-containing protein (VCP) was previously shown to be a proviral host factor for several viruses from different viral families such as Flaviviridae, Picornaviridae, and Herpesviridae. VCP was shown to affect trafficking of Sindbis virus receptor and functions as a component of Semliki Forest virus (SFV) replicase compartment. However, the role of this cellular protein was not evaluated during replication of alphaviruses including chikungunya virus (CHIKV). Using siRNA, chemical inhibitors, and trans-replication assays, we show here that VCP is a proviral factor involved in the replication of CHIKV. Immunofluorescence assays confirmed that VCP co-localized with non-structural replicase proteins but not with dsRNA foci possibly due to VCP epitope unavailability. VCP pro-viral role is also observed with other alphaviruses such as o’nyong’nyong virus (ONNV) and SFV in different human cell lines. VCP proviral roles on several viral families now extend to replication of alphaviruses CHIKV and ONNV, emphasizing the pivotal role of VCP in virus–host interaction biology.",2019 Sep 24,"['Carissimo, Guillaume', 'Chan, Yi-Hao', 'Utt, Age', 'Chua, Tze-Kwang', 'Bakar, Farhana Abu', 'Merits, Andres', 'Ng, Lisa F. P.']",Front Microbiol,,,True
ad68e5f84b2feb5e50d799f3a1eedf293fb19961,PMC,IFNL4 Genotypes Predict Clearance of RNA Viruses in Rwandan Children With Upper Respiratory Tract Infections,http://dx.doi.org/10.3389/fcimb.2019.00340,PMC6787560,31637221,CC BY,"Polymorphisms in the interferon lambda gene locus (IFNL) such as the IFNL4 genetic variants rs12979860 and rs368234815 are predictive of resolution of hepatitis C virus infection, but information about the impact of these variants in other infections is scarce. This study aimed at determining the potential impact of IFNL4 variation for the clearance of respiratory tract pathogens in Rwandan children (≤5 years old, n = 480) seeking medical care for acute respiratory infections. Nasopharyngeal swabs were retrieved from all children at the first hospital referral and from 161 children at follow-up visits 2 weeks later. The swabs were analyzed for pathogens by real-time PCR and for host cell IFNL4 genotype at rs12979860 and rs368234815. Approximately 1/3 of the children were homozygous for the rs12979860 T allele and the rs368234815 ΔG allele, which are overrepresented in subjects of African descent. These IFNL4 variants were significantly associated with reduced clearance of RNA viruses. Our results suggest that IFNL4 genotypes that are common among subjects of African descent may determine inefficacious clearance of RNA viruses from the respiratory tract.",2019 Oct 4,"['Rugwizangoga, Belson', 'Andersson, Maria E.', 'Kabayiza, Jean-Claude', 'Nilsson, Malin S.', 'Ármannsdóttir, Brynja', 'Aurelius, Johan', 'Nilsson, Staffan', 'Hellstrand, Kristoffer', 'Lindh, Magnus', 'Martner, Anna']",Front Cell Infect Microbiol,,,True
3e337761fbc884c46ccd834207c310a1b78f0e42,PMC,Luciferase-Based Detection of Antibodies for the Diagnosis of HPV-Associated Head and Neck Squamous Cell Carcinoma,http://dx.doi.org/10.3390/diagnostics9030089,PMC6787723,31390810,CC BY,"Point-of-care tests are needed for the screening of head and neck squamous cell carcinoma (HNSCC) and other malignancies. Luciferase immunoprecipitation systems (LIPS), employing light-emitting proteins, were used to examine serum antibodies against several cancer-associated targets in blood donor controls and subjects with colon cancer (CC) and HNSCC. The assessment of antibodies against the wild type p53 tumor antigen showed that approximately 25% of the CC and 20% of the HNSCC patients were seropositive. In addition, humoral responses against two p53 mutants, p53-R175H and p53-R273H, generally tracked the antibody responses seen against wild type p53. Analysis of antibodies against highly specific biomarkers of HPV-16-associated malignancy, E2, E6, and E7 oncoproteins, revealed no seropositivity in blood donors and CC patients. However, 45% (9/20) of the HNSCC patients showed E6 seropositivity, which overlapped all the detectable E2 (40%; 8/20) and E7 seropositive subjects (35%; 7/20). Using neodymium magnets, ultrarapid LIPSTICKS testing of HPV-16 E6 antibodies in <60 s per HNSCC sample demonstrated almost the same diagnostic performance (40% sensitivity and 100% specificity) as LIPS testing in 2.5 h. While additional improvements and standardization are needed, these results highlight the possibility of using these approaches for the diagnosis of HPV-16-associated HNSCC.",2019 Aug 6,"['Burbelo, Peter D.', 'Chaturvedi, Adrija', 'Notkins, Abner L.', 'Gunti, Sreenivasulu']",Diagnostics (Basel),,,True
a74504e83f52c1ed91c0e52adc5af8830d71ae5f,PMC,Impact and clinical profiles of Mycoplasma pneumoniae co-detection in childhood community-acquired pneumonia,http://dx.doi.org/10.1186/s12879-019-4426-0,PMC6788033,31601192,CC BY,"BACKGROUND: Increasing number of hospitalized children with community acquired pneumonia (CAP) is co-detected with Mycoplasma pneumoniae (Mp). The clinical characteristics and impact of Mp co-detected with other bacterial and/or viral pathogens remain poorly understood. The purpose of this study was to evaluate the demographic and clinical features of CAP children with Mp mono-detection and Mp co-detection. METHODS: A total of 4148 hospitalized children with CAP were recruited from January to December 2017 at the Children’s Hospital of Hebei Province, affiliated to Hebei Medical University. A variety of respiratory viruses, bacteria and Mp were detected using multiple modalities. The demographic and clinical features of CAP children with Mp mono-detection and Mp co-detection were recorded and analyzed. RESULTS: Among the 110 CAP children with Mp positive, 42 (38.18%) of them were co-detected with at least one other pathogen. Co-detection was more common among children aged ≤3 years. No significant differences were found in most clinical symptoms, complications, underlying conditions and disease severity parameters among various etiological groups, with the following exceptions. First, prolonged duration of fever, lack of appetite and runny nose were more prevalent among CAP children with Mp-virus co-detection. Second, Mp-virus (excluding HRV) co-detected patients were more likely to present with prolonged duration of fever. Third, patients co-detected with Mp-bacteria were more likely to have abnormal blood gases. Additionally, CAP children with Mp-HRV co-detection were significantly more likely to report severe runny nose compared to those with Mp mono-detection. CONCLUSION: Mp co-detection with viral and/or bacterial pathogens is common in clinical practice. However, there are no apparent differences between Mp mono-detection and Mp co-detections in terms of clinical features and disease severity.",2019 Oct 11,"['Zhao, Meng-chuan', 'Wang, Le', 'Qiu, Fang-zhou', 'Zhao, Li', 'Guo, Wei-wei', 'Yang, Shuo', 'Feng, Zhi-shan', 'Li, Gui-xia']",BMC Infect Dis,,,True
9cd6f7eef808b5362ce36f7b92a50cb28238136c,PMC,Isolation and Identification of Porcine Epidemic Diarrhea Virus and Its Effect on Host Natural Immune Response,http://dx.doi.org/10.3389/fmicb.2019.02272,PMC6788300,31636617,CC BY,"Porcine epidemic diarrhea (PED) is a highly infectious intestinal disease caused by porcine epidemic diarrhea virus (PEDV). A PEDV strain was isolated from the piglet intestinal tract in Vero cells in Jiangsu Province, designated as the JS-A strain. PEDV was identified as the isolated virus by cytopathology, immunofluorescence assay, western blotting, transmission electron microscopy, and sequence analysis. The full-length genome of the JS-A isolate and the S gene were systematically analyzed, indicating that PEDV JS-A belongs to the G2a subtype, which is closely related to the prevalent PEDV in many countries and different from many current vaccines. Animal regression tests showed that piglets that are orally infected with the virus continue to develop diarrhea with yellowish and unpleasant odors. Further, piglets showed reduced food consumption and weight loss in the challenged group, while there were no abnormalities in the control group. In addition, Toll-like receptors (TLRs), RIG-I, and the downstream medium gene in the intestinal mucosa of newborn pigs infected with PEDV JS-A strain were studied. The neonatal Fc receptor (FcRn) was the only IgG transport receptor and protected IgG from degradation. Therefore, PEDV JS-A infection might inhibit FcRn expression by down-regulating TLRs and downstream signaling molecules. Taken together, isolation of the JS-A variant contributes to evolutionary analysis of the diarrhea virus. Further, the experimental infection model lays a foundation for further research related to vaccine development and the antiviral natural immune response of infected piglets, which helps us to better understand PEDV pathogenesis and immune mechanism.",2019 Oct 4,"['Qian, Shaoju', 'Zhang, Weida', 'Jia, Xiangchao', 'Sun, Zhijian', 'Zhang, Yang', 'Xiao, Yuncai', 'Li, Zili']",Front Microbiol,,,True
7a8f035845b43c4e3b01a3034bff85a7ae9b8dfc,PMC,Zika Vaccine Development—Current Progress and Challenges for the Future,http://dx.doi.org/10.3390/tropicalmed4030104,PMC6789600,31337115,CC BY,"Zika virus is an emergent pathogen that gained significant importance during the epidemic in South and Central America as unusual and alarming complications of infection were recognized. Although initially considered a self-limited benign infection, a panoply of neurologic complications were recognized including a Guillain–Barré-like syndrome and in-utero fetal infection causing microcephaly, blindness, and other congenital neurologic complications. Numerous Zika virus vaccines were developed, with nine different vaccines representing five different platforms entered into clinical trials, one progressing to Phase II. Here we review the current landscape and challenges confronting Zika virus vaccine development.",2019 Jul 14,"Maslow, Joel N.",Trop Med Infect Dis,,,True
da841082920197ef43a5d5bdb05b38ed7cccf9fe,PMC,Antiviral Effect of Lithium Chloride and Diammonium Glycyrrhizinate on Porcine Deltacoronavirus In Vitro,http://dx.doi.org/10.3390/pathogens8030144,PMC6789623,31505777,CC BY,"Porcine deltacoronavirus (PDCoV) is an emerging global swine virus that has a propensity for interspecies transmission. It was identified in Hong Kong in 2012. Given that neither specific antiviral drugs nor vaccines are available for newly emerging porcine deltacoronavirus, searching for effective antiviral drugs is a high priority. In this study, lithium chloride (LiCl) and diammonium glycyrrhizinate (DG), which are host-acting antivirals (HAAs), were tested against PDCoV. We found that LiCl and DG inhibited PDCoV replication in LLC-PK1 cells in a dose-dependent manner. The antiviral effects of LiCl and DG occurred at the early stage of PDCoV replication, and DG also inhibited virus attachment to the cells. Moreover, both drugs inhibited PDCoV-induced apoptosis in LLC-PK1 cells. This study suggests LiCl and DG as new drugs for the treatment of PDCoV infection.",2019 Sep 9,"['Zhai, Xiaofeng', 'Wang, Shilei', 'Zhu, Mengyan', 'He, Wei', 'Pan, Zhongzhou', 'Su, Shuo']",Pathogens,,,True
c9c113247df3932d3dbbabc25b9b927efa03c115,PMC,Moving from Empirical to Rational Vaccine Design in the ‘Omics’ Era,http://dx.doi.org/10.3390/vaccines7030089,PMC6789792,31416125,CC BY,"An ideal vaccine provides long lasting protection against a pathogen by eliciting a well-rounded immune response which engages both innate and adaptive immunity. However, we have a limited understanding of how components of innate immunity, antibody and cell-mediated adaptive immunity interact and function together at a systems level. With advances in high-throughput ‘Omics’ methodologies it has become possible to capture global changes in the host, at a cellular and molecular level, that are induced by vaccination and infection. Analysis of these datasets has shown the promise of discovering mechanisms behind vaccine mediated protection, immunological memory, adverse effects as well as development of more efficient antigens and adjuvants. In this review, we will discuss how systems vaccinology takes advantage of new technology platforms and big data analysis, to enable the rational development of better vaccines.",2019 Aug 14,"['Sharma, Mansi', 'Krammer, Florian', 'García-Sastre, Adolfo', 'Tripathi, Shashank']",Vaccines (Basel),,,True
09b0945d4963d363bb670d75070c19a328fbfce6,PMC,Paramyxo- and Coronaviruses in Rwandan Bats,http://dx.doi.org/10.3390/tropicalmed4030099,PMC6789848,31269631,CC BY,"A high diversity of corona- and paramyxoviruses have been detected in different bat species at study sites worldwide, including Africa, however no biosurveillance studies from Rwanda have been reported. In this study, samples from bats collected from caves in Ruhengeri, Rwanda, were tested for the presence of corona- and paramyxoviral RNA using reverse transcription PCR assays. Positive results were further characterized by DNA sequencing and phylogenetic analysis. In addition to morphological identification of bat species, we also did molecular confirmation of species identities, contributing to the known genetic database available for African bat species. We detected a novel Betacoronavirus in two Geoffroy’s horseshoe bats (Rhinolophus clivosus) bats. We also detected several different paramyxoviral species from various insectivorous bats. One of these viral species was found to be homologous to the genomes of viruses belonging to the Jeilongvirus genus. Additionally, a Henipavirus-related sequence was detected in an Egyptian rousette fruit bat (Rousettus aegyptiacus). These results expand on the known diversity of corona- and paramyxoviruses and their geographical distribution in Africa.",2019 Jul 2,"['Markotter, Wanda', 'Geldenhuys, Marike', 'Jansen van Vuren, Petrus', 'Kemp, Alan', 'Mortlock, Marinda', 'Mudakikwa, Antoine', 'Nel, Louis', 'Nziza, Julius', 'Paweska, Janusz', 'Weyer, Jacqueline']",Trop Med Infect Dis,,,True
09ed89677cb73f2993d2c1eb0282fa829d377095,PMC,Paramyxo- and Coronaviruses in Rwandan Bats,http://dx.doi.org/10.3390/tropicalmed4030099,PMC6789848,31269631,CC BY,"A high diversity of corona- and paramyxoviruses have been detected in different bat species at study sites worldwide, including Africa, however no biosurveillance studies from Rwanda have been reported. In this study, samples from bats collected from caves in Ruhengeri, Rwanda, were tested for the presence of corona- and paramyxoviral RNA using reverse transcription PCR assays. Positive results were further characterized by DNA sequencing and phylogenetic analysis. In addition to morphological identification of bat species, we also did molecular confirmation of species identities, contributing to the known genetic database available for African bat species. We detected a novel Betacoronavirus in two Geoffroy’s horseshoe bats (Rhinolophus clivosus) bats. We also detected several different paramyxoviral species from various insectivorous bats. One of these viral species was found to be homologous to the genomes of viruses belonging to the Jeilongvirus genus. Additionally, a Henipavirus-related sequence was detected in an Egyptian rousette fruit bat (Rousettus aegyptiacus). These results expand on the known diversity of corona- and paramyxoviruses and their geographical distribution in Africa.",2019 Jul 2,"['Markotter, Wanda', 'Geldenhuys, Marike', 'Jansen van Vuren, Petrus', 'Kemp, Alan', 'Mortlock, Marinda', 'Mudakikwa, Antoine', 'Nel, Louis', 'Nziza, Julius', 'Paweska, Janusz', 'Weyer, Jacqueline']",Trop Med Infect Dis,,,False
ca8476b6429d8fb8ea4d3e094c222fbd5a7f6304,PMC,Understudied Factors Influencing Fc-Mediated Immune Responses against Viral Infections,http://dx.doi.org/10.3390/vaccines7030103,PMC6789852,31480293,CC BY,"Antibodies play a crucial role in host defense against viruses, both by preventing infection and by controlling viral replication. Besides their capacity to neutralize viruses, antibodies also exert their antiviral effects by crystallizable fragment (Fc)-mediated effector mechanisms. This involves a bridge between innate and adaptive immune systems, wherein antibodies form immune complexes that drive numerous innate immune effector functions, including antibody-dependent cellular cytotoxicity, antibody-dependent complement-mediated lysis, and antibody-dependent phagocytosis. Here, we review certain mechanisms that modulate these antibody-mediated effector functions against virally infected cells, such as viral glycoprotein shedding, viral glycoprotein internalization, antibody cooperativity, and antibody glycosylation. These mechanisms can either protect viral replication or enhance infected cell clearance. Here we discuss the importance of these understudied factors in modulating Fc-mediated effector functions.",2019 Aug 30,"['Anand, Sai Priya', 'Finzi, Andrés']",Vaccines (Basel),,,True
3b3bb498af6f356f4389825f4f3b026edcaef4f0,PMC,Semi-quantitative visual assessment of chest radiography is associated with clinical outcomes in critically ill patients,http://dx.doi.org/10.1186/s12931-019-1201-0,PMC6790038,31606045,CC BY,"BACKGROUND: Respiratory pathology is a major driver of mortality in the intensive care unit (ICU), even in the absence of a primary respiratory diagnosis. Prior work has demonstrated that a visual scoring system applied to chest radiographs (CXR) is associated with adverse outcomes in ICU patients with Acute Respiratory Distress Syndrome (ARDS). We hypothesized that a simple, semi-quantitative CXR score would be associated with clinical outcomes for the general ICU population, regardless of underlying diagnosis. METHODS: All individuals enrolled in the Registry of Critical Illness at Brigham and Women’s Hospital between June 2008 and August 2018 who had a CXR within 24 h of admission were included. Each patient’s CXR was assigned an opacification score of 0–4 in each of four quadrants with the total score being the sum of all four quadrants. Multivariable negative binomial, logistic, and Cox regression, adjusted for age, sex, race, immunosuppression, a history of chronic obstructive pulmonary disease, a history of congestive heart failure, and APACHE II scores, were used to assess the total score’s association with ICU length of stay (LOS), duration of mechanical ventilation, in-hospital mortality, 60-day mortality, and overall mortality, respectively. RESULTS: A total of 560 patients were included. Higher CXR scores were associated with increased mortality; for every one-point increase in score, in-hospital mortality increased 10% (OR 1.10, CI 1.05–1.16, p < 0.001) and 60-day mortality increased by 12% (OR 1.12, CI 1.07–1.17, p < 0.001). CXR scores were also independently associated with both ICU length of stay (rate ratio 1.06, CI 1.04–1.07, p < 0.001) and duration of mechanical ventilation (rate ratio 1.05, CI 1.02–1.07, p < 0.001). CONCLUSIONS: Higher values on a simple visual score of a patient’s CXR on admission to the medical ICU are associated with increased in-hospital mortality, 60-day mortality, overall mortality, length of ICU stay, and duration of mechanical ventilation.",2019 Oct 12,"['Mason, Stefanie E.', 'Dieffenbach, Paul B.', 'Englert, Joshua A.', 'Rogers, Angela A.', 'Massaro, Anthony F.', 'Fredenburgh, Laura E.', 'Higuera, Angelica', 'Pinilla-Vera, Mayra', 'Vilas, Marta', 'San Jose Estepar, Raul', 'Washko, George R.', 'Baron, Rebecca M.', 'Ash, Samuel Y.']",Respir Res,,,True
78cc0a828b438df4987059241b39f933a1dfdfd0,PMC,Sample descriptors linked to metagenomic sequencing data from human and animal enteric samples from Vietnam,http://dx.doi.org/10.1038/s41597-019-0215-2,PMC6794271,31615980,CC BY,"There is still limited information on the diversity of viruses co-circulating in humans and animals. Here, we report data obtained from a large field collection of enteric samples taken from humans, pigs, rodents and other mammal hosts in Vietnam between 2012 and 2016. Each of 2100 stool or rectal swab samples was subjected to virally-enriched agnostic metagenomic sequencing; the short read sequence data are accessible from the European Nucleotide Archive (ENA). We link the sequence data to metadata on host type and demography and geographic location, distinguishing hospital patients, members of a cohort identified as a high risk of zoonotic infections (e.g. abattoir workers, rat traders) and animals. These data are suitable for further studies of virus diversity and virus discovery in humans and animals from Vietnam and to identify viruses found in multiple hosts that are potentially zoonotic.",2019 Oct 15,"['Woolhouse, Mark', 'Ashworth, Jordan', 'Bogaardt, Carlijn', 'Tue, Ngo Tri', 'Baker, Steve', 'Thwaites, Guy', 'Phuc, Tran My']",Sci Data,,,True
e7482377b6836c860bc4ea714ea5dd757a293ad0,PMC,Protective Efficacy of Different Live Attenuated Infectious Bronchitis Virus Vaccination Regimes Against Challenge With IBV Variant-2 Circulating in the Middle East,http://dx.doi.org/10.3389/fvets.2019.00341,PMC6794438,31649942,CC BY,"Six vaccination regimes using classical (Mass-type) and variant (IB-VAR2 and IB-793B) live vaccines were evaluated against Middle Eastern variant-2 infectious bronchitis virus challenge. Six groups of SPF chicks (30 birds/group) were vaccinated using prime-boost regimes at day-1 and day-14 using; IB-M41:IB-VAR2, IB-VAR2:IB-VAR2, IB-VAR2:IB-M41, IB-Ma5:IB-793B, IB-793B:IB-793B, and IB-793B:IB-Ma5, respectively. Ciliostasis and lesion scores were evaluated at day-5 after each vaccination. Birds were challenged intranasally at 14-day post 2nd vaccination using 10(5)EID(50)/0.1 ml/bird of wild-type IBV (Eg/1212B/2012). At 3, 5, and 7-day post challenge (DPC) virus shedding was monitored by real-time RT-PCR. Five chicks/group were euthanized at 7DPC for ciliostasis and lesion scoring and histopathology was conducted on 3 chicks/group. Seroconversion was evaluated at 14 DPC. All groups primed with the 793B vaccine showed relatively higher ciliostasis scores compared to other groups. The IB-VAR2 vaccinated groups showed the highest protection rates (80–100%) and high protection score (67.6–73.2%) compared to the 793B vaccine groups (50–60%). The virus shedding was significantly reduced at 3 and 5DPC in groups received the IBV-VAR2 (prime or booster) compared to those received the 793B vaccine. In conclusion, the homologous IBV-VAR2 vaccine showed superior results compared to 793B or Mass-type vaccines confirming the importance of IBV vaccine seed homology to the circulating IBV strains.",2019 Oct 9,"['Sultan, Hesham A.', 'Ali, Ahmed', 'El Feil, Wael K.', 'Bazid, Abdel Hamid I.', 'Zain El-Abideen, Mohamed A.', 'Kilany, Walid H.']",Front Vet Sci,,,True
5a7eaaf283f1005f17f029f26a9ec33eebe566bc,PMC,Tissue-specific responses of antioxidant pathways to poor hygiene conditions in growing pigs divergently selected for feed efficiency,http://dx.doi.org/10.1186/s12917-019-2107-2,PMC6794813,31619228,CC BY,"BACKGROUND: Poor hygiene of housing induces a systemic inflammatory response. Because inflammation and oxidative stress are processes that can sustain each other, the ways pigs are able to activate their antioxidant defenses are critical for production performance and health during periods when the immune system is solicited. Selection for production performance can also influence reactive oxygen species (ROS) production and expression levels of genes involved in cellular response to oxidative stress in different tissues. To establish the extent by which poor hygiene and selection for feed efficiency affected redox status, pigs divergently selected for residual feed intake (RFI) were housed in poor or good hygiene during 6 weeks. At the end, blood was collected in all pigs, and half of them were killed for tissue sampling. The remaining pigs were reared in good hygiene conditions during a recovery period of 7–8 weeks. RESULTS: At week 6, poor hygiene was associated with a lower total antioxidant capacity assessed by plasma ferric reducing ability in all pigs, and with greater plasma levels of hydrogen peroxides in the high RFI pigs (less efficient). Adipose tissue of high RFI pigs exhibited higher activities of catalase and glutathione reductase, and greater thiobarbituric acid reactive substances (TBARS) concentrations when compared with the low RFI pigs (more efficient). Poor hygiene conditions activated the antioxidant enzymes activities (glutathione reductase, superoxide dismutase and catalase) in adipose tissue of both lines, but led to higher ROS production by mature adipocytes isolated from the high RFI pigs only. In liver and muscle, there were only minor changes in antioxidant molecules due to genetics and hygiene conditions. After the resilience period, adipose tissue of pigs previously challenged by poor hygiene maintained higher antioxidant enzyme activities, and for the high RFI line, displayed higher TBARS concentrations. CONCLUSIONS: Pigs selected for improved feed efficiency showed a lower susceptibility to oxidative stress induced by poor hygiene conditions. This could led to a lower inflammatory response and less impaired growth when these pigs are facing sanitary challenges during the production period.",2019 Oct 16,"['Sierżant, K.', 'Perruchot, M-H.', 'Merlot, E.', 'Le Floc’h, N.', 'Gondret, F.']",BMC Vet Res,,,True
8d67e5c1683885f28d8b023224e65998d8e73411,PMC,"Evaluation of the efficacy of a trivalent vaccine mixture against a triple challenge with Mycoplasma hyopneumoniae, PCV2, and PRRSV and the efficacy comparison of the respective monovalent vaccines against a single challenge",http://dx.doi.org/10.1186/s12917-019-2091-6,PMC6794872,31619295,CC BY,"BACKGROUND: The objective of this study was to assess the efficacy of a trivalent vaccine mixture and compare it to the respective monovalent vaccines against Mycoplasma hyopneumoniae, porcine circovirus type 2 (PCV2), and porcine reproductive and respiratory syndrome virus (PRRSV). RESULTS: Pigs that were triple challenged with M. hyopneumoniae, PCV2, and PRRSV following vaccination with the trivalent vaccine mixture exhibited a significantly better growth performance when compared to unvaccinated and challenged pigs. A statistical difference was not found when comparing pig populations which were vaccinated with the trivalent vaccine followed by a triple challenge and pigs vaccinated with monovalent M hyopneumoniae vaccine followed by mycoplasmal single challenge in the following areas: M. hyopneumoniae nasal shedding, the number of M. hyopneumoniae-specific interferon-γ secreting cells (IFN-γ-SC), and mycoplasmal lung lesion scores. Pigs vaccinated with the trivalent vaccine mixture followed by a triple challenge resulted in a similar reduction of PCV2 viremia, an increase in the number of PCV2-specific IFN-γ-SC and reduction in interstitial lung lesion scores when compared to pigs vaccinated with a PCV-2 vaccine and challenged with PCV2 only. Lastly, there was a significant difference in the reduction of PRRSV viremia, an increase in PRRSV-specific IFN-γ-SC and a reduction of interstitial lung lesion scores between pigs vaccinated with the trivalent vaccine mixture followed by a triple challenge and pigs vaccinated with a monovalent PRRSV vaccine followed by PRRSV challenge only. CONCLUSION: The trivalent vaccine mixture was efficacious against a triple challenge of M. hyopneumoniae, PCV2, and PRRSV. The trivalent vaccine mixture, however, did not result in equal protection when compared against each respective monovalent vaccine, with the largest vaccine occurring within PRRSV.",2019 Oct 16,"['Oh, Taehwan', 'Park, Kee Hwan', 'Yang, Siyeon', 'Jeong, Jiwoon', 'Kang, Ikjae', 'Park, Changhoon', 'Chae, Chanhee']",BMC Vet Res,,,True
37ce6523b9d7806ed86759bc36b5c6efcfa6dda3,PMC,Fine epitope mapping of glycoprotein Gn in Guertu virus,http://dx.doi.org/10.1371/journal.pone.0223978,PMC6795428,31618247,CC BY,"Guertu virus (GTV) is a tick-borne phleboviruses (TBPVs) which belongs to the genus Banyangvirus in the family of Phenuiviridae. In vitro and in vivo studies of GTV demonstrated that it was able to infect animal and human cell lines and could cause pathological lesions in mice. Glycoproteins (GP, including Gn and Gc) on the surface of Guertu virus (GTV) could bind to receptors on host cells and induce protective immunity in the host, but knowledge is now lacking on the information of B cell epitopes (BCEs) present on GTV-GP protein. The aim of this study was to identify all BCEs on Gn of the GTV DXM strain using rabbit pAbs against GTV-Gn. Seven fine BCEs and two antigenic peptides (APs) from nine reactive 16mer-peptides were identified, which are E(Gn)1 ((2)PIICEGLTHS(11)), E(Gn)2 ((135)CSQDSGT(141)), E(Gn)3 ((165)IP EDVF(170)), E(Gn)4 ((169)VFQEL K(174)), E(Gn)5 ((187)IDGILFN(193)), E(Gn)6 ((223)QTKWIQ(228)), E(Gn)7 ((237)CHKDGIGPC(245)), AP-8 ((299)GVRVRPKCYGFSRMMA(314)) and AP-9 ((355)CASH FCSSAESGKKNT(370)), of which six of mapped BCEs were recognized by the IgG-positive sheep serum obtained from sheep GTV-infected naturally. Multiple sequence alignments (MSA) based on each mapped BCE motif identified that the most of identified BCEs and APs are highly conserved among 10 SFTSV strains from different countries and lineages that share relatively close evolutionary relationships with GTV. The fine epitope mapping of the GTV-Gn would provide basic data with which to explore the GTV-Gn antigen structure and pathogenic mechanisms, and it could lay the foundation for the design and development of a GTV multi-epitope peptide vaccine and detection antigen.",2019 Oct 16,"['Zhang, Jingyuan', 'Moming, Abulimiti', 'Yue, Xihong', 'Shen, Shu', 'Liu, Dongliang', 'Xu, Wan-xiang', 'Wang, Chen', 'Ding, Juntao', 'Li, Yijie', 'Deng, Fei', 'Zhang, Yujiang', 'Sun, Surong']",PLoS One,,,True
afd83a90943b4d9103daaf9507267b65e257c85c,PMC,TSEN54 missense variant in Standard Schnauzers with leukodystrophy,http://dx.doi.org/10.1371/journal.pgen.1008411,PMC6795476,31584937,CC BY,"We report a hereditary leukodystrophy in Standard Schnauzer puppies. Clinical signs occurred shortly after birth or started at an age of under 4 weeks and included apathy, dysphoric vocalization, hypermetric ataxia, intension tremor, head tilt, circling, proprioceptive deficits, seizures and ventral strabismus consistent with a diffuse intracranial lesion. Magnetic resonance imaging revealed a diffuse white matter disease without mass effect. Macroscopically, the cerebral white matter showed a gelatinous texture in the centrum semiovale. A mild hydrocephalus internus was noted. Histopathologically, a severe multifocal reduction of myelin formation and moderate diffuse edema without inflammation was detected leading to the diagnosis of leukodystrophy. Combined linkage analysis and homozygosity mapping in two related families delineated critical intervals of approximately 29 Mb. The comparison of whole genome sequence data of one affected Standard Schnauzer to 221 control genomes revealed a single private homozygous protein changing variant in the critical intervals, TSEN54:c.371G>A or p.(Gly124Asp). TSEN54 encodes the tRNA splicing endonuclease subunit 54. In humans, several variants in TSEN54 were reported to cause different types of pontocerebellar hypoplasia. The genotypes at the c.371G>A variant were perfectly associated with the leukodystrophy phenotype in 12 affected Standard Schnauzers and almost 1000 control dogs from different breeds. These results suggest that TSEN54:c.371G>A causes the leukodystrophy. The identification of a candidate causative variant enables genetic testing so that the unintentional breeding of affected Standard Schnauzers can be avoided in the future. Our findings extend the known genotype-phenotype correlation for TSEN54 variants.",2019 Oct 4,"['Störk, Theresa', 'Nessler, Jasmin', 'Anderegg, Linda', 'Hünerfauth, Enrice', 'Schmutz, Isabelle', 'Jagannathan, Vidhya', 'Kyöstilä, Kaisa', 'Lohi, Hannes', 'Baumgärtner, Wolfgang', 'Tipold, Andrea', 'Leeb, Tosso']",PLoS Genet,,,True
e9cc0f100e2de3e0eede526b1182c4de51334f78,PMC,TSEN54 missense variant in Standard Schnauzers with leukodystrophy,http://dx.doi.org/10.1371/journal.pgen.1008411,PMC6795476,31584937,CC BY,"We report a hereditary leukodystrophy in Standard Schnauzer puppies. Clinical signs occurred shortly after birth or started at an age of under 4 weeks and included apathy, dysphoric vocalization, hypermetric ataxia, intension tremor, head tilt, circling, proprioceptive deficits, seizures and ventral strabismus consistent with a diffuse intracranial lesion. Magnetic resonance imaging revealed a diffuse white matter disease without mass effect. Macroscopically, the cerebral white matter showed a gelatinous texture in the centrum semiovale. A mild hydrocephalus internus was noted. Histopathologically, a severe multifocal reduction of myelin formation and moderate diffuse edema without inflammation was detected leading to the diagnosis of leukodystrophy. Combined linkage analysis and homozygosity mapping in two related families delineated critical intervals of approximately 29 Mb. The comparison of whole genome sequence data of one affected Standard Schnauzer to 221 control genomes revealed a single private homozygous protein changing variant in the critical intervals, TSEN54:c.371G>A or p.(Gly124Asp). TSEN54 encodes the tRNA splicing endonuclease subunit 54. In humans, several variants in TSEN54 were reported to cause different types of pontocerebellar hypoplasia. The genotypes at the c.371G>A variant were perfectly associated with the leukodystrophy phenotype in 12 affected Standard Schnauzers and almost 1000 control dogs from different breeds. These results suggest that TSEN54:c.371G>A causes the leukodystrophy. The identification of a candidate causative variant enables genetic testing so that the unintentional breeding of affected Standard Schnauzers can be avoided in the future. Our findings extend the known genotype-phenotype correlation for TSEN54 variants.",2019 Oct 4,"['Störk, Theresa', 'Nessler, Jasmin', 'Anderegg, Linda', 'Hünerfauth, Enrice', 'Schmutz, Isabelle', 'Jagannathan, Vidhya', 'Kyöstilä, Kaisa', 'Lohi, Hannes', 'Baumgärtner, Wolfgang', 'Tipold, Andrea', 'Leeb, Tosso']",PLoS Genet,,,False
52075e1e28bc2952fb7a2360fae88c76b36c722a,PMC,Presumptive Development of Fibrotic Lung Disease From Bordetella bronchiseptica and Post-infectious Bronchiolitis Obliterans in a Dog,http://dx.doi.org/10.3389/fvets.2019.00352,PMC6795681,31649945,CC BY,"A 7-month-old Miniature Poodle acquired from a pet store developed cough and subsequently respiratory distress compatible with Bordetella bronchiseptica infection. Partial but incomplete resolution of clinical signs and thoracic radiographic/computed tomographic imaging lesions were noted with use of susceptibility-guided antimicrobials. Additionally, a concern for an infectious nidus led to left cranial lung lobectomy at 9 months of age. Histopathology predominantly revealed polypoid and constrictive bronchiolitis obliterans (i.e., small airway disease). Intermittent antimicrobial administration over the next 5 years failed to blunt progressive clinical signs. At 8 years, necropsy confirmed severe airway-centered interstitial fibrosis. This pattern of fibrosis was strongly suggestive of underlying small airway disease as the trigger. In retrospect, post-infectious bronchiolitis obliterans (PIBO), a syndrome in young children caused by pulmonary infections but not yet recognized in pet dogs, likely initiated a pathway of fibrosis in this dog. In dogs with risk factors for community-acquired pathogens such as Bordetella bronchiseptica, PIBO is a differential diagnosis with development of severe, persistent respiratory signs incompletely responsive to appropriate antimicrobials. Untreated PIBO may lead to airway-centered interstitial fibrosis. Future study is required to determine if targeted therapy of PIBO could alter the course of end-stage pulmonary fibrosis.",2019 Oct 10,"['Jaffey, Jared A.', 'Harmon, Mark', 'Masseau, Isabelle', 'Williams, Kurt J.', 'Reinero, Carol']",Front Vet Sci,,,True
88f00457544e21a031e4b643cd71affe006a5d7e,PMC,Clinical outcomes of patients treated with intravenous zanamivir for severe influenza A(H1N1)pdm09 infection: a case report series,http://dx.doi.org/10.1186/s12879-019-4530-1,PMC6796355,31619209,CC BY,"BACKGROUND: Intravenous (IV) zanamivir could be a suitable alternative for the treatment of severe influenza A(H1N1)pdm09 infection in patients who are unable to take oral or inhaled medication, for example, those on mechanical ventilation and extracorporeal membrane oxygenation (ECMO). However, data on the clinical outcomes of such patients is limited. CASE PRESENTATION: We report the clinical outcomes of four patients who were admitted at the intensive care unit during the 2017–2018 influenza season with severe sepsis (SOFA score > 11) and acute respiratory distress syndrome requiring ECMO and mechanical ventilation. Two patients were immune-compromised. The A(H1N1)pdm09 genome was confirmed by polymerase chain reaction (PCR) on nasopharyngeal specimen swabs prior to administration of IV zanamivir at a dose of 600 mg twice daily. Weekly qualitative PCR analysis was done to monitor viral clearance, with zanamivir treatment being discontinued upon receipt of negative results. In addition, the patients were managed for concomitant multidrug-resistant bacterial infections, with infection resolution confirmed with blood cultures. The median time for zanamivir treatment was 10 days (IQR 10–17). The clinical outcome was favourable with all four patients surviving and improving clinically. All four patients achieved viral clearance of A(H1N1)pdm09 genome, and resolution of multidrug-resistant bacterial infections. CONCLUSIONS: IV zanamivir could be a good therapeutic option in patients with severe influenza A(H1N1)pdm09 infection who are unable to take oral or aerosolised antiviral medication. We recommend prospective randomized control trials to support this hypothesis.",2019 Oct 16,"['Torti, Carlo', 'Mazzitelli, Maria', 'Longhini, Federico', 'Garofalo, Eugenio', 'Bruni, Andrea', 'Giancotti, Aida', 'Barreca, Giorgio Settimo', 'Quirino, Angela', 'Liberto, Maria Carla', 'Serapide, Francesca', 'Matera, Giovanni', 'Trecarichi, Enrico Maria', 'Navalesi, Paolo', None]",BMC Infect Dis,,,True
712c86986815982dc6d918b660f70f5e05616643,PMC,Respiratory syncytial virus nonstructural proteins 1 and 2: Exceptional disrupters of innate immune responses,http://dx.doi.org/10.1371/journal.ppat.1007984,PMC6797084,31622448,CC BY,"Human respiratory syncytial virus (RSV) is the most important cause of acute lower respiratory tract disease in infants worldwide. As a first line of defense against respiratory infections, innate immune responses, including the production of type I and III interferons (IFNs), play an important role. Upon infection with RSV, multiple pattern recognition receptors (PRRs) can recognize RSV-derived pathogen-associated molecular patterns (PAMPs) and mount innate immune responses. Retinoic-acid-inducible gene-I (RIG-I) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) have been identified as important innate receptors to mount type I IFNs during RSV infection. However, type I IFN levels remain surprisingly low during RSV infection despite strong viral replication. The poor induction of type I IFNs can be attributed to the cooperative activity of 2 unique, nonstructural (NS) proteins of RSV, i.e., NS1 and NS2. These viral proteins have been shown to suppress both the production and signaling of type I and III IFNs by counteracting a plethora of key host innate signaling proteins. Moreover, increasing numbers of IFN-stimulated genes (ISGs) are being identified as targets of the NS proteins in recent years, highlighting an underexplored protein family in the identification of NS target proteins. To understand the diverse effector functions of NS1 and NS2, Goswami and colleagues proposed the hypothesis of the NS degradasome (NSD) complex, a multiprotein complex made up of, at least, NS1 and NS2. Furthermore, the crystal structure of NS1 was resolved recently and, remarkably, identified NS1 as a structural paralogue of the RSV matrix protein. Unfortunately, no structural data on NS2 have been published so far. In this review, we briefly describe the PRRs that mount innate immune responses upon RSV infection and provide an overview of the various effector functions of NS1 and NS2. Furthermore, we discuss the ubiquitination effector functions of NS1 and NS2, which are in line with the hypothesis that the NSD shares features with the canonical 26S proteasome.",2019 Oct 17,"['Sedeyn, Koen', 'Schepens, Bert', 'Saelens, Xavier']",PLoS Pathog,,,True
7c28a8c1dfe1e35116be3903159e5230bd0b9403,PMC,Viral respiratory infections and the oropharyngeal bacterial microbiota in acutely wheezing children,http://dx.doi.org/10.1371/journal.pone.0223990,PMC6797130,31622414,CC BY,"Acute viral wheeze in children is a major cause of hospitalisation and a major risk factor for the development of asthma. However, the role of the respiratory tract microbiome in the development of acute wheeze is unclear. To investigate whether severe wheezing episodes in children are associated with bacterial dysbiosis in the respiratory tract, oropharyngeal swabs were collected from 109 children with acute wheezing attending the only tertiary paediatric hospital in Perth, Australia. The bacterial community from these samples was explored using next generation sequencing and compared to samples from 75 non-wheezing controls. No significant difference in bacterial diversity was observed between samples from those with wheeze and healthy controls. Within the wheezing group, attendance at kindergarten or preschool was however, associated with increased bacterial diversity. Rhinovirus (RV) infection did not have a significant effect on bacterial community composition. A significant difference in bacterial richness was observed between children with RV-A and RV-C infection, however this is likely due to the differences in age group between the patient cohorts. The bacterial community within the oropharynx was found to be diverse and heterogeneous. Age and attendance at day care or kindergarten were important factors in driving bacterial diversity. However, wheeze and viral infection were not found to significantly relate to the bacterial community. Bacterial airway microbiome is highly variable in early life and its role in wheeze remains less clear than viral influences.",2019 Oct 17,"['Cuthbertson, Leah', 'Oo, Stephen W. C.', 'Cox, Michael J.', 'Khoo, Siew-Kim', 'Cox, Des W.', 'Chidlow, Glenys', 'Franks, Kimberley', 'Prastanti, Franciska', 'Borland, Meredith L.', 'Gern, James E.', 'Smith, David W.', 'Bizzintino, Joelene A.', 'Laing, Ingrid A.', 'Le Souëf, Peter N.', 'Moffatt, Miriam F.', 'Cookson, William O. C.']",PLoS One,,,True
c1c3f2e22e7af46ef16acb516bdbaa8118d3c992,PMC,Viral respiratory infections and the oropharyngeal bacterial microbiota in acutely wheezing children,http://dx.doi.org/10.1371/journal.pone.0223990,PMC6797130,31622414,CC BY,"Acute viral wheeze in children is a major cause of hospitalisation and a major risk factor for the development of asthma. However, the role of the respiratory tract microbiome in the development of acute wheeze is unclear. To investigate whether severe wheezing episodes in children are associated with bacterial dysbiosis in the respiratory tract, oropharyngeal swabs were collected from 109 children with acute wheezing attending the only tertiary paediatric hospital in Perth, Australia. The bacterial community from these samples was explored using next generation sequencing and compared to samples from 75 non-wheezing controls. No significant difference in bacterial diversity was observed between samples from those with wheeze and healthy controls. Within the wheezing group, attendance at kindergarten or preschool was however, associated with increased bacterial diversity. Rhinovirus (RV) infection did not have a significant effect on bacterial community composition. A significant difference in bacterial richness was observed between children with RV-A and RV-C infection, however this is likely due to the differences in age group between the patient cohorts. The bacterial community within the oropharynx was found to be diverse and heterogeneous. Age and attendance at day care or kindergarten were important factors in driving bacterial diversity. However, wheeze and viral infection were not found to significantly relate to the bacterial community. Bacterial airway microbiome is highly variable in early life and its role in wheeze remains less clear than viral influences.",2019 Oct 17,"['Cuthbertson, Leah', 'Oo, Stephen W. C.', 'Cox, Michael J.', 'Khoo, Siew-Kim', 'Cox, Des W.', 'Chidlow, Glenys', 'Franks, Kimberley', 'Prastanti, Franciska', 'Borland, Meredith L.', 'Gern, James E.', 'Smith, David W.', 'Bizzintino, Joelene A.', 'Laing, Ingrid A.', 'Le Souëf, Peter N.', 'Moffatt, Miriam F.', 'Cookson, William O. C.']",PLoS One,,,False
fc212dc72c96fcedc6e724394fe67ff77087a5d5,PMC,Strategies for Success. Viral Infections and Membraneless Organelles,http://dx.doi.org/10.3389/fcimb.2019.00336,PMC6797609,31681621,CC BY,"Regulation of RNA homeostasis or “RNAstasis” is a central step in eukaryotic gene expression. From transcription to decay, cellular messenger RNAs (mRNAs) associate with specific proteins in order to regulate their entire cycle, including mRNA localization, translation and degradation, among others. The best characterized of such RNA-protein complexes, today named membraneless organelles, are Stress Granules (SGs) and Processing Bodies (PBs) which are involved in RNA storage and RNA decay/storage, respectively. Given that SGs and PBs are generally associated with repression of gene expression, viruses have evolved different mechanisms to counteract their assembly or to use them in their favor to successfully replicate within the host environment. In this review we summarize the current knowledge about the viral regulation of SGs and PBs, which could be a potential novel target for the development of broad-spectrum antiviral therapies.",2019 Oct 11,"['Gaete-Argel, Aracelly', 'Márquez, Chantal L.', 'Barriga, Gonzalo P.', 'Soto-Rifo, Ricardo', 'Valiente-Echeverría, Fernando']",Front Cell Infect Microbiol,,,True
359e2466c6424f9b5ca2f4eb46fbf2a011a9a6c5,PMC,Sustained Egr-1 Response via p38 MAP Kinase Signaling Modulates Early Immune Responses of Dendritic Cells Parasitized by Toxoplasma gondii,http://dx.doi.org/10.3389/fcimb.2019.00349,PMC6797980,31681626,CC BY,"As a response to a diverse array of external stimuli, early growth response protein 1 (Egr-1) plays important roles in the transcriptional regulation of inflammation and the cellular immune response. However, a number of intracellular pathogens colonize immune cells and the implication of Egr-1 in the host-pathogen interplay has remained elusive. Here, we have characterized the Egr-1 responses of primary murine and human dendritic cells (DCs) upon challenge with the obligate intracellular parasite Toxoplasma gondii. We report that live intracellular parasites induce a sustained high expression of Egr-1 in DCs, different from the immediate-early Egr-1 response to parasite lysates, inactivated parasites or LPS. Moreover, a distinct nuclear localization of elevated amounts of Egr-1 protein was detected in infected DCs, but not in by-stander DCs. The ERK1/2 MAPK signaling pathway mediated the canonical immediate-early Egr-1 response to soluble antigens in a MyD88/TLR-dependent fashion. In contrast, a non-canonical extended Egr-1 response that relied primarily on p38 MAPK signaling was induced by intracellular parasites and was exhibited similarly by MyD88-deficient and wildtype DCs. The extended phase Egr-1 response was dramatically reduced upon challenge of DCs with T. gondii parasites deficient in GRA24, a secreted p38-interacting protein. Further, Egr-1-silenced primary DCs maintained their migratory responses upon T. gondii challenge. Importantly, Egr-1 silencing led to elevated expression of co-stimulatory molecules (CD40, CD80) in Toxoplasma-infected DCs and in LPS-challenged immature DCs, indicating that Egr-1 responses suppressed maturation of DCs. Moreover, the IL-12 and IL-2 responses of Toxoplasma-challenged DCs were modulated in a GRA24-dependent fashion. Jointly, the data show that the Egr-1 responses of DCs to microbial external stimuli and intracellular stimuli can be selectively mediated by ERK1/2 or p38 MAPK signaling, and that Egr-1 can act as an intrinsic negative modulator of maturation in primary DCs.",2019 Oct 11,"['ten Hoeve, Arne L.', 'Hakimi, Mohamed-Ali', 'Barragan, Antonio']",Front Cell Infect Microbiol,,,True
3518ccc719fac30ad9a95930985cb000a0018ae5,PMC,What makes health systems resilient against infectious disease outbreaks and natural hazards? Results from a scoping review,http://dx.doi.org/10.1186/s12889-019-7707-z,PMC6798426,31623594,CC BY,"BACKGROUND: The 2014–2016 Ebola outbreak was a wake-up call regarding the critical importance of resilient health systems. Fragile health systems can become overwhelmed during public health crises, further exacerbating the human, economic, and political toll. Important work has been done to describe the general attributes of a health system resilient to these crises, and the next step will be to identify the specific capacities that health systems need to develop and maintain to achieve resiliency. METHODS: We conducted a scoping review of the literature to identify recurring themes and capacities needed for health system resiliency to infectious disease outbreaks and natural hazards and any existing implementation frameworks that highlight these capacities. We also sought to identify the overlap of the identified themes and capacities with those highlighted in the World Health Organization’s Joint External Evaluation. Sources of evidence included PubMed, Web of Science, OAIster, and the websites of relevant major public health organizations. RESULTS: We identified 16 themes of health system resilience, including: the need to develop plans for altered standards of care during emergencies, the need to develop plans for post-event recovery, and a commitment to quality improvement. Most of the literature described the general attributes of a resilient health system; no implementation frameworks were identified that could translate these elements into specific capacities that health system actors can employ to improve resilience to outbreaks and natural hazards in a variety of settings. CONCLUSIONS: An implementation-oriented health system resilience framework could help translate the important components of a health system identified in this review into specific capacities that actors in the health system could work to develop to improve resilience to public health crises. However, there remains a need to further refine the concept of resilience so that health systems can simultaneously achieve sustainable transformations in healthcare practice and health service delivery as well as improve their preparedness for emergencies.",2019 Oct 17,"['Nuzzo, Jennifer B.', 'Meyer, Diane', 'Snyder, Michael', 'Ravi, Sanjana J.', 'Lapascu, Ana', 'Souleles, Jon', 'Andrada, Carolina I.', 'Bishai, David']",BMC Public Health,,,True
96f0cf86f03bfe173c1b161ae5936757fb6a9b0e,PMC,A field‐deployable insulated isothermal RT‐PCR assay for identification of influenza A (H7N9) shows good performance in the laboratory,http://dx.doi.org/10.1111/irv.12646,PMC6800302,31487118,CC BY,"BACKGROUND: Avian influenza A (H7N9) remains circulating in China. For countries at risk of introduction of H7N9, such as Vietnam, early detection of H7N9 virus is essential for the early containment of the virus. Insulated isothermal reverse transcriptase PCR (iiRT‐PCR) is a portable PCR system that can be deployed under field conditions to identify pathogens at the sampling site. Applying PCR at the sampling site will greatly reduce the time to obtain a diagnostic result which allows the veterinary authority to take immediate action to contain disease spreading. OBJECTIVE: To determine analytical and diagnostic sensitivity and specificity of the portable iiRT‐PCR for H7N9 virus detection. METHODS: A panel of 59 virus isolates, including H7N9, avian influenza viruses of subtype H1 to H13, swine and human influenza viruses, Newcastle disease virus, and infectious bursal disease virus, were tested by H7 and N9 iiRT‐PCR reagents, using probes and primers specific to H7 or N9, in comparison with laboratory‐based real‐time RT‐PCR assays to determine analytical sensitivity and specificity. Fifty oropharyngeal samples from experimentally infected chicken and ducks with H7N9 and 50 non‐infected control swabs were tested by the H7 iiRT‐PCR to determine diagnostic sensitivity and specificity. RESULTS: The H7 and N9 iiRT‐PCR reagents yielded comparable levels of analytical sensitivity and specificity with real‐time RT‐PCR for the detection of H7N9 virus. Diagnostic sensitivity and specificity of H7 iiRT‐PCR were 98% and 100%, respectively. CONCLUSION: The observed high sensitivity and specificity of iiRT‐PCR for H7N9 detection show its potential for early detection of H7N9 in risk‐based surveillance.",2019 Nov 5,"['Inui, Ken', 'Nguyen, Tung', 'Tseng, Hsin‐Jou', 'Tsai, ChuanFu Mark', 'Tsai, Yun‐Long', 'Chung, Simon', 'Padungtod, Pawin', 'Zhu, Huachen', 'Guan, Yi', 'Kalpravidh, Wantanee', 'Claes, Filip']",Influenza Other Respir Viruses,,,True
4a57f2f528842aa5dc0fd95788f524bc9b4b03bd,PMC,Improving immunological insights into the ferret model of human viral infectious disease,http://dx.doi.org/10.1111/irv.12687,PMC6800307,31583825,CC BY,"Ferrets are a well‐established model for studying both the pathogenesis and transmission of human respiratory viruses and evaluation of antiviral vaccines. Advanced immunological studies would add substantial value to the ferret models of disease but are hindered by the low number of ferret‐reactive reagents available for flow cytometry and immunohistochemistry. Nevertheless, progress has been made to understand immune responses in the ferret model with a limited set of ferret‐specific reagents and assays. This review examines current immunological insights gained from the ferret model across relevant human respiratory diseases, with a focus on influenza viruses. We highlight key knowledge gaps that need to be bridged to advance the utility of ferrets for immunological studies.",2019 Nov 3,"['Wong, Julius', 'Layton, Daniel', 'Wheatley, Adam K.', 'Kent, Stephen J.']",Influenza Other Respir Viruses,,,True
84bdc3ec8b4e9ba8a0c4eac3105208064704d50f,PMC,New frontiers in applied veterinary point‐of‐capture diagnostics: Toward early detection and control of zoonotic influenza,http://dx.doi.org/10.1111/irv.12648,PMC6800308,31334612,CC BY,"Among the chief limitations in achieving early detection and control of animal‐origin influenza of pandemic potential in high‐risk livestock populations is the existing lag time between sample collection and diagnostic result. Advances in molecular diagnostics are permitting deployment of affordable, rapid, highly sensitive, and specific point‐of‐capture assays, providing opportunities for targeted surveillance driving containment strategies with potentially compelling returns on investment. Interrupting disease transmission at source holds promise of disrupting cycles of animal‐origin influenza incursion to endemicity and limiting impact on animal production, food security, and public health. Adoption of new point‐of‐capture diagnostics should be undertaken in the context of promoting robust veterinary services systems and parallel support for operationalizing pre‐authorized plans and communication strategies that will ensure that the full potential of these new platforms is realized.",2019 Nov 23,"['Schar, Daniel', 'Padungtod, Pawin', 'Tung, Nguyen', 'O’Leary, Michael', 'Kalpravidh, Wantanee', 'Claes, Filip']",Influenza Other Respir Viruses,,,True
86dfb3c7e72f3aec8bc2f425f4fd5c4c3aab2ca4,PMC,Evaluation of bioaerosol samplers for the detection and quantification of influenza virus from artificial aerosols and influenza virus–infected ferrets,http://dx.doi.org/10.1111/irv.12678,PMC6800310,31541519,CC BY,"BACKGROUND: Bioaerosol sampling devices are necessary for the characterization of infectious bioaerosols emitted by naturally‐infected hosts with acute respiratory virus infections. Assessment of these devices under multiple experimental conditions will provide insight for device use. OBJECTIVES: The primary objective of this study was to assess and compare bioaerosol sampling devices using a) an in vitro, environmentally‐controlled artificial bioaerosol system at a range of different RH conditions and b) an in vivo bioaerosol system of influenza virus‐infected ferrets under controlled environmental conditions. Secondarily, we also sought to examine the impact of NSAIDs on bioaerosol emission in influenza virus‐infected ferrets to address its potential as a determinant of bioaerosol emission. METHODS: We examined the performance of low and moderate volume bioaerosol samplers for the collection of viral RNA and infectious influenza virus in vitroand in vivo using artificial bioaerosols and the ferret model of influenza virus infection. The following samplers were tested: the polytetrafluoroethylene filter (PTFE filter), the 2‐stage National Institute of Occupational Safety and Health cyclone sampler (NIOSH cyclone sampler) and the 6‐stage viable Andersen impactor (Andersen impactor). RESULTS: The PTFE filter and NIOSH cyclone sampler collected similar amounts of viral RNA and infectious virus from artificially‐generated aerosols under a range of relative humidities (RH). Using the ferret model, the PTFE filter, NIOSH cyclone sampler and the Andersen impactor collected up to 3.66 log(10)copies of RNA/L air, 3.84 log(10)copies of RNA/L air and 6.09 log(10)copies of RNA/L air respectively at peak recovery. Infectious virus was recovered from the PTFE filter and NIOSH cyclone samplers on the peak day of viral RNA recovery. CONCLUSION: The PTFE filter and NIOSH cyclone sampler are useful for influenza virus RNA and infectious virus collection and may be considered for clinical and environmental settings.",2019 Nov 21,"['Bekking, Christian', 'Yip, Lily', 'Groulx, Nicolas', 'Doggett, Nathan', 'Finn, Mairead', 'Mubareka, Samira']",Influenza Other Respir Viruses,,,True
15f3676a843fc2b08f47c1e0c49d78f63519caeb,PMC,Feline immunodeficiency virus in puma: Estimation of force of infection reveals insights into transmission,http://dx.doi.org/10.1002/ece3.5584,PMC6802039,31641451,CC BY,"1. Determining parameters that govern pathogen transmission (such as the force of infection, FOI), and pathogen impacts on morbidity and mortality, is exceptionally challenging for wildlife. Vital parameters can vary, for example across host populations, between sexes and within an individual's lifetime. 2. Feline immunodeficiency virus (FIV) is a lentivirus affecting domestic and wild cat species, forming species‐specific viral–host associations. FIV infection is common in populations of puma (Puma concolor), yet uncertainty remains over transmission parameters and the significance of FIV infection for puma mortality. In this study, the age‐specific FOI of FIV in pumas was estimated from prevalence data, and the evidence for disease‐associated mortality was assessed. 3. We fitted candidate models to FIV prevalence data and adopted a maximum likelihood method to estimate parameter values in each model. The models with the best fit were determined to infer the most likely FOI curves. We applied this strategy for female and male pumas from California, Colorado, and Florida. 4. When splitting the data by sex and area, our FOI modeling revealed no evidence of disease‐associated mortality in any population. Both sex and location were found to influence the FOI, which was generally higher for male pumas than for females. For female pumas at all sites, and male pumas from California and Colorado, the FOI did not vary with puma age, implying FIV transmission can happen throughout life; this result supports the idea that transmission can occur from mothers to cubs and also throughout adult life. For Florida males, the FOI was a decreasing function of puma age, indicating an increased risk of infection in the early years, and a decreased risk at older ages. 5. This research provides critical insight into pathogen transmission and impact in a secretive and solitary carnivore. Our findings shed light on the debate on whether FIV causes mortality in wild felids like puma, and our approach may be adopted for other diseases and species. The methodology we present can be used for identifying likely transmission routes of a pathogen and also estimating any disease‐associated mortality, both of which can be difficult to establish for wildlife diseases in particular.",2019 Sep 26,"['Reynolds, Jennifer J. H.', 'Carver, Scott', 'Cunningham, Mark W.', 'Logan, Ken A.', 'Vickers, Winston', 'Crooks, Kevin R.', 'VandeWoude, Sue', 'Craft, Meggan E.']",Ecol Evol,,,True
9c14ddc3ada412e1f66c1aec73f8ca320f3b2cee,PMC,Safety and efficacy of ChAdOx1 RVF vaccine against Rift Valley fever in pregnant sheep and goats,http://dx.doi.org/10.1038/s41541-019-0138-0,PMC6802222,31646004,CC BY,"Rift Valley fever virus (RVFV) is a zoonotic mosquito-borne virus that was first discovered in Kenya in 1930 and has since spread to become endemic in much of Africa and the Arabian Peninsula. Rift Valley fever (RVF) causes recurrent outbreaks of febrile illness associated with high levels of mortality and poor outcomes during pregnancy—including foetal malformations, spontaneous abortion and stillbirths—in livestock, and associated with miscarriage in humans. No vaccines are available for human use and those licensed for veterinary use have potential drawbacks, including residual virulence that may contraindicate their use in pregnancy. To address this gap, we previously developed a simian adenovirus vectored vaccine, ChAdOx1 RVF, that encodes RVFV envelope glycoproteins. ChAdOx1 RVF is fully protective against RVF in non-pregnant livestock and is also under development for human use. Here, we now demonstrate that when administered to pregnant sheep and goats, ChAdOx1 RVF is safe, elicits high titre RVFV neutralizing antibody, and provides protection against viraemia and foetal loss, although this protection is not as robust for the goats. In addition, we provide a description of RVFV challenge in pregnant goats and contrast this to the pathology observed in pregnant sheep. Together, our data further support the ongoing development of ChAdOx1 RVF vaccine for use in livestock and humans.",2019 Oct 18,"['Stedman, Anna', 'Wright, Daniel', 'Wichgers Schreur, Paul J.', 'Clark, Madeleine H. A.', 'Hill, Adrian V. S.', 'Gilbert, Sarah C.', 'Francis, Michael J.', 'van Keulen, Lucien', 'Kortekaas, Jeroen', 'Charleston, Bryan', 'Warimwe, George M.']",NPJ Vaccines,,,False
be960dfd985a96e972597ef4de9d0872ab708f99,PMC,Safety and efficacy of ChAdOx1 RVF vaccine against Rift Valley fever in pregnant sheep and goats,http://dx.doi.org/10.1038/s41541-019-0138-0,PMC6802222,31646004,CC BY,"Rift Valley fever virus (RVFV) is a zoonotic mosquito-borne virus that was first discovered in Kenya in 1930 and has since spread to become endemic in much of Africa and the Arabian Peninsula. Rift Valley fever (RVF) causes recurrent outbreaks of febrile illness associated with high levels of mortality and poor outcomes during pregnancy—including foetal malformations, spontaneous abortion and stillbirths—in livestock, and associated with miscarriage in humans. No vaccines are available for human use and those licensed for veterinary use have potential drawbacks, including residual virulence that may contraindicate their use in pregnancy. To address this gap, we previously developed a simian adenovirus vectored vaccine, ChAdOx1 RVF, that encodes RVFV envelope glycoproteins. ChAdOx1 RVF is fully protective against RVF in non-pregnant livestock and is also under development for human use. Here, we now demonstrate that when administered to pregnant sheep and goats, ChAdOx1 RVF is safe, elicits high titre RVFV neutralizing antibody, and provides protection against viraemia and foetal loss, although this protection is not as robust for the goats. In addition, we provide a description of RVFV challenge in pregnant goats and contrast this to the pathology observed in pregnant sheep. Together, our data further support the ongoing development of ChAdOx1 RVF vaccine for use in livestock and humans.",2019 Oct 18,"['Stedman, Anna', 'Wright, Daniel', 'Wichgers Schreur, Paul J.', 'Clark, Madeleine H. A.', 'Hill, Adrian V. S.', 'Gilbert, Sarah C.', 'Francis, Michael J.', 'van Keulen, Lucien', 'Kortekaas, Jeroen', 'Charleston, Bryan', 'Warimwe, George M.']",NPJ Vaccines,,,False
5148320311832c95cb1c8b4fa32569e5a7945ff9,PMC,Safety and efficacy of ChAdOx1 RVF vaccine against Rift Valley fever in pregnant sheep and goats,http://dx.doi.org/10.1038/s41541-019-0138-0,PMC6802222,31646004,CC BY,"Rift Valley fever virus (RVFV) is a zoonotic mosquito-borne virus that was first discovered in Kenya in 1930 and has since spread to become endemic in much of Africa and the Arabian Peninsula. Rift Valley fever (RVF) causes recurrent outbreaks of febrile illness associated with high levels of mortality and poor outcomes during pregnancy—including foetal malformations, spontaneous abortion and stillbirths—in livestock, and associated with miscarriage in humans. No vaccines are available for human use and those licensed for veterinary use have potential drawbacks, including residual virulence that may contraindicate their use in pregnancy. To address this gap, we previously developed a simian adenovirus vectored vaccine, ChAdOx1 RVF, that encodes RVFV envelope glycoproteins. ChAdOx1 RVF is fully protective against RVF in non-pregnant livestock and is also under development for human use. Here, we now demonstrate that when administered to pregnant sheep and goats, ChAdOx1 RVF is safe, elicits high titre RVFV neutralizing antibody, and provides protection against viraemia and foetal loss, although this protection is not as robust for the goats. In addition, we provide a description of RVFV challenge in pregnant goats and contrast this to the pathology observed in pregnant sheep. Together, our data further support the ongoing development of ChAdOx1 RVF vaccine for use in livestock and humans.",2019 Oct 18,"['Stedman, Anna', 'Wright, Daniel', 'Wichgers Schreur, Paul J.', 'Clark, Madeleine H. A.', 'Hill, Adrian V. S.', 'Gilbert, Sarah C.', 'Francis, Michael J.', 'van Keulen, Lucien', 'Kortekaas, Jeroen', 'Charleston, Bryan', 'Warimwe, George M.']",NPJ Vaccines,,,True
8bb39b846b0bd9548526bad9e74fed1e4a8ac4cb,PMC,Molecular epidemiology of respiratory viruses in commercial chicken flocks in Pakistan from 2014 through to 2016,http://dx.doi.org/10.1186/s12917-019-2103-6,PMC6802313,31638995,CC BY,"BACKGROUND: Viral diseases are a matter of great concern for poultry farmers in Pakistan. Multiple common viral respiratory diseases (CVRDs) cause huge economic losses in the poultry industry. The prevalence of CVRDs in many countries, including Pakistan, is not clearly understood. RESULTS: Incidences of 5 chicken respiratory viruses: avian influenza virus (AIV), Newcastle disease virus (NDV/AAVV-1), infectious bronchitis virus (IBV), avian metapneumovirus (aMPV) and infectious laryngotracheitis virus (ILTV) were assessed on commercial Pakistani farms with respiratory problems from 2014 through to 2016. While AIV and AAVV-1 were frequently detected (16 to 17% of farms), IBV and aMPV were rarely detected (in 3 to 5% of farms) and ILTV was not detected. We characterized H9 AIV of the G1 lineage, genotype VII AAVV-1, GI-13 IBV, and type B aMPV strains with very little genetic variability in the 2-year study period. Co-infections with AIV and AAVV-1 were common and wild type AAVV-1 was detected despite the use of vaccines. Control measures to limit the virus burden in chicken flocks are discussed. CONCLUSIONS: Our data shows that AIV (H9), AAVV-1, IBV and aMPV are prevalent in commercial poultry in Pakistan. Further studies are necessary to assess circulating strains, economic losses caused by infections and coinfections of these pathogens, and the costs and benefits of countermeasures. Furthermore, veterinarians and farmers should be informed of the pathogens circulating in the field and hence advised on the use of vaccines.",2019 Oct 21,"['Umar, Sajid', 'Teillaud, Angélique', 'Aslam, Hassan Bin', 'Guerin, Jean-Luc', 'Ducatez, Mariette F.']",BMC Vet Res,,,True
2f5fb10362e86dbf302d8677f4c106c5287bf704,PMC,Unraveling the Molecular Mechanism of Traditional Chinese Medicine: Formulas Against Acute Airway Viral Infections as Examples,http://dx.doi.org/10.3390/molecules24193505,PMC6804036,31569633,CC BY,"Herbal medicine, including traditional Chinese medicine (TCM), is widely used worldwide. Herbs and TCM formulas contain numerous active molecules. Basically, they are a kind of cocktail therapy. Herb-drug, herb-food, herb-herb, herb-microbiome, and herb-disease interactions are complex. There is potential for both benefit and harm, so only after understanding more of their mechanisms and clinical effects can herbal medicine and TCM be helpful to users. Many pharmacologic studies have been performed to unravel the molecular mechanisms; however, basic and clinical studies of good validity are still not enough to translate experimental results into clinical understanding and to provide tough evidence for better use of herbal medicines. There are still issues regarding the conflicting pharmacologic effects, pharmacokinetics, drug interactions, adverse and clinical effects of herbal medicine and TCM. Understanding study validation, pharmacologic effects, drug interactions, indications and clinical effects, adverse effects and limitations, can all help clinicians in providing adequate suggestions to patients. At present, it would be better to use herbs and TCM formulas according to their traditional indications matching the disease pathophysiology and their molecular mechanisms. To unravel the molecular mechanisms and understand the benefits and harms of herbal medicine and TCM, there is still much work to be done.",2019 Sep 27,"['Eng, Yi Shin', 'Lee, Chien Hsing', 'Lee, Wei Chang', 'Huang, Ching Chun', 'Chang, Jung San']",Molecules,,,True
09d2a697632210efee7bf9fe6ee07b66bb7248f2,PMC,Novel Antiretroviral Structures from Marine Organisms,http://dx.doi.org/10.3390/molecules24193486,PMC6804230,31561445,CC BY,"In spite of significant advancements and success in antiretroviral therapies directed against HIV infection, there is no cure for HIV, which scan persist in a human body in its latent form and become reactivated under favorable conditions. Therefore, novel antiretroviral drugs with different modes of actions are still a major focus for researchers. In particular, novel lead structures are being sought from natural sources. So far, a number of compounds from marine organisms have been identified as promising therapeutics for HIV infection. Therefore, in this paper, we provide an overview of marine natural products that were first identified in the period between 2013 and 2018 that could be potentially used, or further optimized, as novel antiretroviral agents. This pipeline includes the systematization of antiretroviral activities for several categories of marine structures including chitosan and its derivatives, sulfated polysaccharides, lectins, bromotyrosine derivatives, peptides, alkaloids, diterpenes, phlorotannins, and xanthones as well as adjuvants to the HAART therapy such as fish oil. We critically discuss the structures and activities of the most promising new marine anti-HIV compounds.",2019 Sep 26,"['Wittine, Karlo', 'Saftić, Lara', 'Peršurić, Željka', 'Kraljević Pavelić, Sandra']",Molecules,,,True
efdfec9626b7961580cf4ecea75e8d4fde27980d,PMC,The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self versus non-self translation,http://dx.doi.org/10.1371/journal.ppat.1008093,PMC6805002,31600344,CC BY,"ISG20 is a broad spectrum antiviral protein thought to directly degrade viral RNA. However, this mechanism of inhibition remains controversial. Using the Vesicular Stomatitis Virus (VSV) as a model RNA virus, we show here that ISG20 interferes with viral replication by decreasing protein synthesis in the absence of RNA degradation. Importantly, we demonstrate that ISG20 exerts a translational control over a large panel of non-self RNA substrates including those originating from transfected DNA, while sparing endogenous transcripts. This activity correlates with the protein’s ability to localize in cytoplasmic processing bodies. Finally, these functions are conserved in the ISG20 murine ortholog, whose genetic ablation results in mice with increased susceptibility to viral infection. Overall, our results posit ISG20 as an important defense factor able to discriminate the self/non-self origins of the RNA through translation modulation.",2019 Oct 10,"['Wu, Nannan', 'Nguyen, Xuan-Nhi', 'Wang, Li', 'Appourchaux, Romain', 'Zhang, Chengfei', 'Panthu, Baptiste', 'Gruffat, Henri', 'Journo, Chloé', 'Alais, Sandrine', 'Qin, Juliang', 'Zhang, Na', 'Tartour, Kevin', 'Catez, Frédéric', 'Mahieux, Renaud', 'Ohlmann, Theophile', 'Liu, Mingyao', 'Du, Bing', 'Cimarelli, Andrea']",PLoS Pathog,,,True
8e30d311467bd72abd1a319a9f841158b6b685fc,PMC,A systematic review and evaluation of Zika virus forecasting and prediction research during a public health emergency of international concern,http://dx.doi.org/10.1371/journal.pntd.0007451,PMC6805005,31584946,CC0,"INTRODUCTION: Epidemic forecasting and prediction tools have the potential to provide actionable information in the midst of emerging epidemics. While numerous predictive studies were published during the 2016–2017 Zika Virus (ZIKV) pandemic, it remains unknown how timely, reproducible, and actionable the information produced by these studies was. METHODS: To improve the functional use of mathematical modeling in support of future infectious disease outbreaks, we conducted a systematic review of all ZIKV prediction studies published during the recent ZIKV pandemic using the PRISMA guidelines. Using MEDLINE, EMBASE, and grey literature review, we identified studies that forecasted, predicted, or simulated ecological or epidemiological phenomena related to the Zika pandemic that were published as of March 01, 2017. Eligible studies underwent evaluation of objectives, data sources, methods, timeliness, reproducibility, accessibility, and clarity by independent reviewers. RESULTS: 2034 studies were identified, of which n = 73 met the eligibility criteria. Spatial spread, R(0) (basic reproductive number), and epidemic dynamics were most commonly predicted, with few studies predicting Guillain-Barré Syndrome burden (4%), sexual transmission risk (4%), and intervention impact (4%). Most studies specifically examined populations in the Americas (52%), with few African-specific studies (4%). Case count (67%), vector (41%), and demographic data (37%) were the most common data sources. Real-time internet data and pathogen genomic information were used in 7% and 0% of studies, respectively, and social science and behavioral data were typically absent in modeling efforts. Deterministic models were favored over stochastic approaches. Forty percent of studies made model data entirely available, 29% provided all relevant model code, 43% presented uncertainty in all predictions, and 54% provided sufficient methodological detail to allow complete reproducibility. Fifty-one percent of predictions were published after the epidemic peak in the Americas. While the use of preprints improved the accessibility of ZIKV predictions by a median of 119 days sooner than journal publication dates, they were used in only 30% of studies. CONCLUSIONS: Many ZIKV predictions were published during the 2016–2017 pandemic. The accessibility, reproducibility, timeliness, and incorporation of uncertainty in these published predictions varied and indicates there is substantial room for improvement. To enhance the utility of analytical tools for outbreak response it is essential to improve the sharing of model data, code, and preprints for future outbreaks, epidemics, and pandemics.",2019 Oct 4,"['Kobres, Pei-Ying', 'Chretien, Jean-Paul', 'Johansson, Michael A.', 'Morgan, Jeffrey J.', 'Whung, Pai-Yei', 'Mukundan, Harshini', 'Del Valle, Sara Y.', 'Forshey, Brett M.', 'Quandelacy, Talia M.', 'Biggerstaff, Matthew', 'Viboud, Cecile', 'Pollett, Simon']",PLoS Negl Trop Dis,,,True
c46b51e5657b05d7af97e9006d2033353ccd9512,PMC,Rotavirus C: prevalence in suckling piglets and development of virus-like particles to assess the influence of maternal immunity on the disease development,http://dx.doi.org/10.1186/s13567-019-0705-4,PMC6805359,31640807,CC BY,"Rotavirus C (RVC) has been detected increasingly in humans and swine in different countries, including the US. It is associated with significant economic losses due to diarrheal disease in nursing piglets. In this study we aimed: (1) to determine the prevalence of RVC in healthy and diarrheic suckling piglets on US farms; and (2) to evaluate if maternal antibody (Ab) levels were associated with protection of newborn suckling piglets against RVC. There was a significantly higher prevalence (p = 0.0002) of litters with diarrhea born to gilts compared with those born to multiparous sows. Of 113 nursing piglet fecal samples tested, 76.1% were RVC RNA positive. Fecal RVC RNA was detected in significantly (p = 0.0419) higher quantities and more frequently in piglets with diarrhea compared with healthy ones (82.5 vs. 69.9%). With the exception of the historic strain Cowden (G1 genotype), field RVC strains do not replicate in cell culture, which is a major impediment for studying RVC pathogenesis and immunity. To circumvent this, we generated RVC virus-like particles (VLPs) for Cowden (G1), RV0104 (G3) and RV0143 (G6) and used them as antigens in ELISA to detect swine RVC Abs in serum and milk from the sows. Using RVC-VLP Ab ELISA we demonstrated that sows with diarrheic litters had significantly lower RVC IgA and IgG Ab titers in milk compared to those with healthy litters. Thus, our data suggest that insufficient lactogenic protection provided by gilts plays a key role in the development of and the increased prevalence of clinical RVC disease.",2019 Oct 22,"['Chepngeno, Juliet', 'Diaz, Annika', 'Paim, Francine C.', 'Saif, Linda J.', 'Vlasova, Anastasia N.']",Vet Res,,,True
357d43fba827a0d33c5810a56e193149df4777f7,PMC,"Outbreak of macrolide-resistant mycoplasma pneumoniae in a primary school in Beijing, China in 2018",http://dx.doi.org/10.1186/s12879-019-4473-6,PMC6805422,31640591,CC BY,"BACKGROUND: On 7th June, 2018, a primary school in Beijing, China notified Shunyi CDC of an outbreak of acute respiratory disease characterized by fever and cough among students and resulting in nine hospitalization cases during the preceding 2 weeks. We started an investigation to identify the etiologic agent, find additional cases, develop and implement control measures. METHODS: We defined probable cases as students, teachers and other staffs in the school developed fever (T ≥ 37.5 °C) with cough or sore throat; or a diagnosis of pneumonia during May 1–June 31, 2018. Confirmed cases were probable cases with Mycoplasma pneumoniae detected in oropharyngeal (OP) swabs by quantitative real-time polymerase chain reaction (qPCR). We searched case by reviewing school absenteeism records and interviewing students, teachers and staff in this school. Oropharyngeal swabs were collected from symptomatic students. Two qPCR) assay, a duplex qPCR assay, and sequencing were performed to determine the pathogen, genotype and macrolide resistance at the gene level, respectively. RESULTS: From May 1st to June 31st, 2018, we identified 55 cases (36 probable and 19 confirmed), of whom 25 (45%) were hospitalized for complications. All cases were students, none of the teachers and other staffs in the school were with similar symptoms. The attack rate (AR) was 3.9% (55/1398) for all students. The cases were mainly male (58%), with an age range of 7–8 years (median: 7 years). 72% (18/25) of inpatients had radiograph findings consistent with pneumonia, and some cases were hospitalized for up to 4 weeks. Pathogen detection results indicated that Mycoplasma pneumonia (M. pneumoniae) P1 type 1 was the causative agent in this outbreak, and the strain harbored one point mutation of A to G at position 2063. CONCLUSIONS: The infections by macrolide-resistant M. pneumoniae are not always mild and pneumonia was common and M. pneumoniae could causes serious complications which require long-term hospitalization. In the future infectious disease prevention and control practice, M. pneumoniae should be paid more attention. It is necessary to establish and improve the pathogen and drug resistance surveillance system in order to prevent and control such mutated strains of M. pneumoniae from causing future outbreaks or epidemics in China.",2019 Oct 22,"['Zhang, Wen-Zeng', 'Zhang, Song-Jian', 'Wang, Quan-Yi', 'Li, Yin-Dong', 'Jing, Hong-Bo', 'Hu, Guang-Yi', 'Wu, Dan']",BMC Infect Dis,,,True
3d9e369c8f1067d661cae62fd1b37257c4e88742,PMC,Recombinant baculovirus expressing the FrC-OVA protein induces protective antitumor immunity in an EG7-OVA mouse model,http://dx.doi.org/10.1186/s13036-019-0207-y,PMC6805443,31649751,CC BY,"BACKGROUND: The baculovirus (BV) Autographa californica multiple nuclear polyhedrosis virus has been used in numerous protein expression systems because of its ability to infect insect cells and serves as a useful vaccination vector with several benefits, such as its low clinical risks and posttranslational modification ability. We recently reported that dendritic cells (DCs) infected with BV stimulated antitumor immunity. The recombinant BV (rBV) also strongly stimulated peptide-specific T-cells and antitumor immunity. In this study, the stimulation of an immune response against EG7-OVA tumors in mice by a recombinant baculovirus-based combination vaccine expressing fragment C-ovalbumin (FrC-OVA-BV; rBV) was evaluated. RESULTS: We constructed an rBV expressing fragment C (FrC) of tetanus toxin containing a promiscuous MHC II-binding sequence and a p30-ovalbumin (OVA) peptide that functions in the MHC I pathway. The results showed that rBV activated the CD8(+) T-cell-mediated response much more efficiently than the wild-type BV (wtBV). Experiments with EG7-OVA tumor mouse models showed that rBV significantly decreased tumor volume and increased survival compared with those in the wild-type BV or FrC-OVA DNA vaccine groups. In addition, a significant antitumor effect of classic prophylactic or therapeutic vaccinations was observed for rBV against EG7-OVA-induced tumors compared with that in the controls. CONCLUSION: Our findings showed that FrC-OVA-BV (rBV) induced antitumor immunity, paving the way for its use in BV immunotherapy against malignancies.",2019 Oct 22,"['Kondou, Keigo', 'Suzuki, Tomoyuki', 'Chang, Myint Oo', 'Takaku, Hiroshi']",J Biol Eng,,,False
00b88130d2a7c8489e209742494303b6731d7544,PMC,Recombinant baculovirus expressing the FrC-OVA protein induces protective antitumor immunity in an EG7-OVA mouse model,http://dx.doi.org/10.1186/s13036-019-0207-y,PMC6805443,31649751,CC BY,"BACKGROUND: The baculovirus (BV) Autographa californica multiple nuclear polyhedrosis virus has been used in numerous protein expression systems because of its ability to infect insect cells and serves as a useful vaccination vector with several benefits, such as its low clinical risks and posttranslational modification ability. We recently reported that dendritic cells (DCs) infected with BV stimulated antitumor immunity. The recombinant BV (rBV) also strongly stimulated peptide-specific T-cells and antitumor immunity. In this study, the stimulation of an immune response against EG7-OVA tumors in mice by a recombinant baculovirus-based combination vaccine expressing fragment C-ovalbumin (FrC-OVA-BV; rBV) was evaluated. RESULTS: We constructed an rBV expressing fragment C (FrC) of tetanus toxin containing a promiscuous MHC II-binding sequence and a p30-ovalbumin (OVA) peptide that functions in the MHC I pathway. The results showed that rBV activated the CD8(+) T-cell-mediated response much more efficiently than the wild-type BV (wtBV). Experiments with EG7-OVA tumor mouse models showed that rBV significantly decreased tumor volume and increased survival compared with those in the wild-type BV or FrC-OVA DNA vaccine groups. In addition, a significant antitumor effect of classic prophylactic or therapeutic vaccinations was observed for rBV against EG7-OVA-induced tumors compared with that in the controls. CONCLUSION: Our findings showed that FrC-OVA-BV (rBV) induced antitumor immunity, paving the way for its use in BV immunotherapy against malignancies.",2019 Oct 22,"['Kondou, Keigo', 'Suzuki, Tomoyuki', 'Chang, Myint Oo', 'Takaku, Hiroshi']",J Biol Eng,,,True
058f046fec5eee31c9ed0bdacd37aa22ba485993,PMC,Clinical outcomes among hospital patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection,http://dx.doi.org/10.1186/s12879-019-4555-5,PMC6805532,31640578,CC BY,"BACKGROUND: Mortality is high among patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. We aimed to determine hospital mortality and the factors associated with it in a cohort of MERS-CoV patients. METHODS: We reviewed hospital records of confirmed cases (detection of virus by polymerase chain reaction from respiratory tract samples) of MERS-CoV patients (n = 63) admitted to Buraidah Central Hospital in Al-Qassim, Saudi Arabia between 2014 and 2017. We abstracted data on demography, vital signs, associated conditions presented on admission, pre-existing chronic diseases, treatment, and vital status. Bi-variate comparisons and multiple logistic regressions were the choice of data analyses. RESULTS: The mean age was 60 years (SD = 18.2); most patients were male (74.6%) and Saudi citizens (81%). All but two patients were treated with Ribavirin plus Interferon. Hospital mortality was 25.4%. Patients who were admitted with septic shock and/or organ failure were significantly more likely to die than patients who were admitted with pneumonia and/or acute respiratory distress syndrome (OR = 47.9, 95% CI = 3.9, 585.5, p-value 0.002). Age, sex, and presence of chronic conditions were not significantly associated with mortality. CONCLUSION: Hospital mortality was 25%; septic shock/organ failure at admittance was a significant predictor of mortality.",2019 Oct 22,"['Habib, Abdulrahman Mohammed G.', 'Ali, Mohamed Abd Elghafour', 'Zouaoui, Baha R.', 'Taha, Mustafa Ahmed H.', 'Mohammed, Bassem Sahsah', 'Saquib, Nazmus']",BMC Infect Dis,,,True
75fef1b487aa86d9904a1860ff8a0bc953a2856c,PMC,Force of infection of Middle East respiratory syndrome in dromedary camels in Kenya,http://dx.doi.org/10.1017/S0950268819001663,PMC6805735,31547888,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic disease transmitted from dromedary camels to people, which can result in outbreaks with human-to-human transmission. Because it is a subclinical infection in camels, epidemiological measures other than prevalence are challenging to assess. This study estimated the force of infection (FOI) of MERS-CoV in camel populations from age-stratified serological data. A cross-sectional study of MERS-CoV was conducted in Kenya from July 2016 to July 2017. Seroprevalence was stratified into four age groups: <1, 1–2, 2–3 and >3 years old. Age-independent and age-dependent linear and quadratic generalised linear models were used to estimate FOI in pastoral and ranching camel herds. Models were compared based on computed AIC values. Among pastoral herds, the age-dependent quadratic FOI was the best fit model, while the age-independent FOI was the best fit for the ranching herd data. FOI provides an indirect estimate of infection risk, which is especially valuable where direct estimates of incidence and other measures of infection are challenging to obtain. The FOIs estimated in this study provide important insight about MERS-CoV dynamics in the reservoir species, and contribute to our understanding of the zoonotic risks of this important public health threat.",2019 Sep 24,"['Gardner, E. G.', 'Kiambi, S.', 'Sitawa, R.', 'Kelton, D.', 'Kimutai, J.', 'Poljak, Z.', 'Tadesse, Z.', 'Von Dobschuetz, S.', 'Wiersma, L.', 'Greer, A. L.']",Epidemiol Infect,,,True
9736b5e6c933555a1afd1a78ec449757476278a6,PMC,"Acceptability of community quarantine in contexts of communicable disease epidemics: perspectives of literate lay people living in Conakry, Guinea",http://dx.doi.org/10.1017/S0950268819001419,PMC6805739,,CC BY,"During the 2014–2016 Ebola epidemic in West Africa, some communities reacted hostilely to the implementation of quarantine measures. This study's aim was to examine the views of lay people in Guinea on the acceptability of community quarantine. From June to August 2016, 302 adults indicated the acceptability of quarantine in 36 scenarios varying as a function of four factors: the infectious disease's level of contagiousness, its level of lethality, the number of cases in the community and whether persons in quarantine are provided with support services. Five clusters were identified: (1) for 18% of the participants, quarantine is never acceptable; (2) 16% considered, in contrast, that quarantine is always acceptable; (3) for 14%, it depends on the disease's level of contagiousness and lethality; (4) 36% based their judgement not only on the levels of contagiousness and lethality, but also on whether those in quarantine are provided with support services; and (5) 16% had no opinion. Interventions to increase voluntary compliance with community quarantine in Guinea must not be ‘one size fits all’, but must be multifaceted and tailored in design and implementation to match the diversity of people's concerns and needs.",2019 Aug 1,"['Kpanake, Lonzozou', 'Leno, Jean-Pierre', 'Sorum, Paul Clay', 'Mullet, Etienne']",Epidemiol Infect,,,True
850d93fde366090620b90ed908b64de128048119,PMC,Risk factors and patterns of household clusters of respiratory viruses in rural Nepal,http://dx.doi.org/10.1017/S0950268819001754,PMC6805793,31607271,CC BY,"Viral pneumonia is an important cause of death and morbidity among infants worldwide. Transmission of non-influenza respiratory viruses in households can inform preventative interventions and has not been well-characterised in South Asia. From April 2011 to April 2012, household members of pregnant women enrolled in a randomised trial of influenza vaccine in rural Nepal were surveyed weekly for respiratory illness until 180 days after birth. Nasal swabs were tested by polymerase chain reaction for respiratory viruses in symptomatic individuals. A transmission event was defined as a secondary case of the same virus within 14 days of initial infection within a household. From 555 households, 825 initial viral illness episodes occurred, resulting in 79 transmission events. The overall incidence of transmission was 1.14 events per 100 person-weeks. Risk of transmission incidence was associated with an index case age 1–4 years (incidence rate ratio (IRR) 2.35; 95% confidence interval (CI) 1.40–3.96), coinfection as initial infection (IRR 1.94; 95% CI 1.05–3.61) and no electricity in household (IRR 2.70; 95% CI 1.41–5.00). Preventive interventions targeting preschool-age children in households in resource-limited settings may decrease the risk of transmission to vulnerable household members, such as young infants.",2019 Oct 14,"['Scott, E. M.', 'Magaret, A.', 'Kuypers, J.', 'Tielsch, J. M.', 'Katz, J.', 'Khatry, S. K.', 'Stewart, L.', 'Shrestha, L.', 'LeClerq, S. C.', 'Englund, J. A.', 'Chu, H. Y.']",Epidemiol Infect,,,True
93838e0710ceaab223e33a42dd309f4b6f90d6b9,PMC,Vitamin A deficiency impairs the immune response to intranasal vaccination and RSV infection in neonatal calves,http://dx.doi.org/10.1038/s41598-019-51684-x,PMC6805856,31641172,CC BY,"Respiratory syncytial virus (RSV) infection is a leading cause of severe acute lower respiratory tract infection in infants and children worldwide. Vitamin A deficiency (VAD) is one of the most prevalent nutrition-related health problems in the world and is a significant risk factor in the development of severe respiratory infections in infants and young children. Bovine RSV (BRSV) is a primary cause of lower respiratory tract disease in young cattle. The calf model of BRSV infection is useful to understand the immune response to human RSV infection. We have previously developed an amphiphilic polyanhydride nanoparticle (NP)-based vaccine (i.e., nanovaccine) encapsulating the fusion and attachment proteins from BRSV (BRSV-NP). Calves receiving a single, intranasal dose of the BRSV-NP vaccine are partially protected from BRSV challenge. Here, we evaluated the impact of VAD on the immune response to the BRSV-NP vaccine and subsequent challenge with BRSV. Our results show that VAD calves are unable to respond to the mucosal BRSV-NP vaccine, are afforded no protection from BRSV challenge and have significant abnormalities in the inflammatory response in the infected lung. We further show that acute BRSV infection negatively impacts serum and liver retinol, rendering even well-nourished individuals susceptible to VAD. Our results support the use of the calf model for elucidating the impact of nutritional status on mucosal immunity and respiratory viral infection in infants and underline the importance of VA in regulating immunity in the respiratory mucosa.",2019 Oct 22,"['McGill, Jodi L.', 'Kelly, Sean M.', 'Guerra-Maupome, Mariana', 'Winkley, Emma', 'Henningson, Jamie', 'Narasimhan, Balaji', 'Sacco, Randy E.']",Sci Rep,,,False
9c3a27a40bb77b4b2663e8033413b4036b1ef43c,PMC,Vitamin A deficiency impairs the immune response to intranasal vaccination and RSV infection in neonatal calves,http://dx.doi.org/10.1038/s41598-019-51684-x,PMC6805856,31641172,CC BY,"Respiratory syncytial virus (RSV) infection is a leading cause of severe acute lower respiratory tract infection in infants and children worldwide. Vitamin A deficiency (VAD) is one of the most prevalent nutrition-related health problems in the world and is a significant risk factor in the development of severe respiratory infections in infants and young children. Bovine RSV (BRSV) is a primary cause of lower respiratory tract disease in young cattle. The calf model of BRSV infection is useful to understand the immune response to human RSV infection. We have previously developed an amphiphilic polyanhydride nanoparticle (NP)-based vaccine (i.e., nanovaccine) encapsulating the fusion and attachment proteins from BRSV (BRSV-NP). Calves receiving a single, intranasal dose of the BRSV-NP vaccine are partially protected from BRSV challenge. Here, we evaluated the impact of VAD on the immune response to the BRSV-NP vaccine and subsequent challenge with BRSV. Our results show that VAD calves are unable to respond to the mucosal BRSV-NP vaccine, are afforded no protection from BRSV challenge and have significant abnormalities in the inflammatory response in the infected lung. We further show that acute BRSV infection negatively impacts serum and liver retinol, rendering even well-nourished individuals susceptible to VAD. Our results support the use of the calf model for elucidating the impact of nutritional status on mucosal immunity and respiratory viral infection in infants and underline the importance of VA in regulating immunity in the respiratory mucosa.",2019 Oct 22,"['McGill, Jodi L.', 'Kelly, Sean M.', 'Guerra-Maupome, Mariana', 'Winkley, Emma', 'Henningson, Jamie', 'Narasimhan, Balaji', 'Sacco, Randy E.']",Sci Rep,,,True
994092a8834f03ac67d9de573345318ef8e254c6,PMC,"Patterns of human social contact and contact with animals in Shanghai, China",http://dx.doi.org/10.1038/s41598-019-51609-8,PMC6805924,31641189,CC BY,"East Asia is as a principal hotspot for emerging zoonotic infections. Understanding the likely pathways for their emergence and spread requires knowledge on human-human and human-animal contacts, but such studies are rare. We used self-completed and interviewer-completed contact diaries to quantify patterns of these contacts for 965 individuals in 2017/2018 in a high-income densely-populated area of China, Shanghai City. Interviewer-completed diaries recorded more social contacts (19.3 vs. 18.0) and longer social contact duration (35.0 vs. 29.1 hours) than self-reporting. Strong age-assortativity was observed in all age groups especially among young participants (aged 7–20) and middle aged participants (25–55 years). 17.7% of participants reported touching animals (15.3% (pets), 0.0% (poultry) and 0.1% (livestock)). Human-human contact was very frequent but contact with animals (especially poultry) was rare although associated with frequent human-human contact. Hence, this densely populated area is more likely to act as an accelerator for human-human spread but less likely to be at the source of a zoonosis outbreak. We also propose that telephone interview at the end of reporting day is a potential improvement of the design of future contact surveys.",2019 Oct 22,"['Zhang, Juanjuan', 'Klepac, Petra', 'Read, Jonathan M.', 'Rosello, Alicia', 'Wang, Xiling', 'Lai, Shengjie', 'Li, Meng', 'Song, Yujian', 'Wei, Qingzhen', 'Jiang, Hao', 'Yang, Juan', 'Lynn, Henry', 'Flasche, Stefan', 'Jit, Mark', 'Yu, Hongjie']",Sci Rep,,,False
513bf780b2d2a5af6a194122cd3dd98c7b507fbe,PMC,"Patterns of human social contact and contact with animals in Shanghai, China",http://dx.doi.org/10.1038/s41598-019-51609-8,PMC6805924,31641189,CC BY,"East Asia is as a principal hotspot for emerging zoonotic infections. Understanding the likely pathways for their emergence and spread requires knowledge on human-human and human-animal contacts, but such studies are rare. We used self-completed and interviewer-completed contact diaries to quantify patterns of these contacts for 965 individuals in 2017/2018 in a high-income densely-populated area of China, Shanghai City. Interviewer-completed diaries recorded more social contacts (19.3 vs. 18.0) and longer social contact duration (35.0 vs. 29.1 hours) than self-reporting. Strong age-assortativity was observed in all age groups especially among young participants (aged 7–20) and middle aged participants (25–55 years). 17.7% of participants reported touching animals (15.3% (pets), 0.0% (poultry) and 0.1% (livestock)). Human-human contact was very frequent but contact with animals (especially poultry) was rare although associated with frequent human-human contact. Hence, this densely populated area is more likely to act as an accelerator for human-human spread but less likely to be at the source of a zoonosis outbreak. We also propose that telephone interview at the end of reporting day is a potential improvement of the design of future contact surveys.",2019 Oct 22,"['Zhang, Juanjuan', 'Klepac, Petra', 'Read, Jonathan M.', 'Rosello, Alicia', 'Wang, Xiling', 'Lai, Shengjie', 'Li, Meng', 'Song, Yujian', 'Wei, Qingzhen', 'Jiang, Hao', 'Yang, Juan', 'Lynn, Henry', 'Flasche, Stefan', 'Jit, Mark', 'Yu, Hongjie']",Sci Rep,,,True
a1ccc7fe4c6c4ae77f84bb48011f0ee0b5900045,PMC,"Patterns of human social contact and contact with animals in Shanghai, China",http://dx.doi.org/10.1038/s41598-019-51609-8,PMC6805924,31641189,CC BY,"East Asia is as a principal hotspot for emerging zoonotic infections. Understanding the likely pathways for their emergence and spread requires knowledge on human-human and human-animal contacts, but such studies are rare. We used self-completed and interviewer-completed contact diaries to quantify patterns of these contacts for 965 individuals in 2017/2018 in a high-income densely-populated area of China, Shanghai City. Interviewer-completed diaries recorded more social contacts (19.3 vs. 18.0) and longer social contact duration (35.0 vs. 29.1 hours) than self-reporting. Strong age-assortativity was observed in all age groups especially among young participants (aged 7–20) and middle aged participants (25–55 years). 17.7% of participants reported touching animals (15.3% (pets), 0.0% (poultry) and 0.1% (livestock)). Human-human contact was very frequent but contact with animals (especially poultry) was rare although associated with frequent human-human contact. Hence, this densely populated area is more likely to act as an accelerator for human-human spread but less likely to be at the source of a zoonosis outbreak. We also propose that telephone interview at the end of reporting day is a potential improvement of the design of future contact surveys.",2019 Oct 22,"['Zhang, Juanjuan', 'Klepac, Petra', 'Read, Jonathan M.', 'Rosello, Alicia', 'Wang, Xiling', 'Lai, Shengjie', 'Li, Meng', 'Song, Yujian', 'Wei, Qingzhen', 'Jiang, Hao', 'Yang, Juan', 'Lynn, Henry', 'Flasche, Stefan', 'Jit, Mark', 'Yu, Hongjie']",Sci Rep,,,True
446f9b4e60a351d21b23f54b58628013aa8697d2,PMC,"Patterns of human social contact and contact with animals in Shanghai, China",http://dx.doi.org/10.1038/s41598-019-51609-8,PMC6805924,31641189,CC BY,"East Asia is as a principal hotspot for emerging zoonotic infections. Understanding the likely pathways for their emergence and spread requires knowledge on human-human and human-animal contacts, but such studies are rare. We used self-completed and interviewer-completed contact diaries to quantify patterns of these contacts for 965 individuals in 2017/2018 in a high-income densely-populated area of China, Shanghai City. Interviewer-completed diaries recorded more social contacts (19.3 vs. 18.0) and longer social contact duration (35.0 vs. 29.1 hours) than self-reporting. Strong age-assortativity was observed in all age groups especially among young participants (aged 7–20) and middle aged participants (25–55 years). 17.7% of participants reported touching animals (15.3% (pets), 0.0% (poultry) and 0.1% (livestock)). Human-human contact was very frequent but contact with animals (especially poultry) was rare although associated with frequent human-human contact. Hence, this densely populated area is more likely to act as an accelerator for human-human spread but less likely to be at the source of a zoonosis outbreak. We also propose that telephone interview at the end of reporting day is a potential improvement of the design of future contact surveys.",2019 Oct 22,"['Zhang, Juanjuan', 'Klepac, Petra', 'Read, Jonathan M.', 'Rosello, Alicia', 'Wang, Xiling', 'Lai, Shengjie', 'Li, Meng', 'Song, Yujian', 'Wei, Qingzhen', 'Jiang, Hao', 'Yang, Juan', 'Lynn, Henry', 'Flasche, Stefan', 'Jit, Mark', 'Yu, Hongjie']",Sci Rep,,,True
d7528a14c4876dbffb163105631a9dea22f20f83,PMC,Glycosylator: a Python framework for the rapid modeling of glycans,http://dx.doi.org/10.1186/s12859-019-3097-6,PMC6806574,31640540,CC BY,"BACKGROUND: Carbohydrates are a class of large and diverse biomolecules, ranging from a simple monosaccharide to large multi-branching glycan structures. The covalent linkage of a carbohydrate to the nitrogen atom of an asparagine, a process referred to as N-linked glycosylation, plays an important role in the physiology of many living organisms. Most software for glycan modeling on a personal desktop computer requires knowledge of molecular dynamics to interface with specialized programs such as CHARMM or AMBER. There are a number of popular web-based tools that are available for modeling glycans (e.g., GLYCAM-WEB (http://https://dev.glycam.org/gp/) or Glycosciences.db (http://www.glycosciences.de/)). However, these web-based tools are generally limited to a few canonical glycan conformations and do not allow the user to incorporate glycan modeling into their protein structure modeling workflow. RESULTS: Here, we present Glycosylator, a Python framework for the identification, modeling and modification of glycans in protein structure that can be used directly in a Python script through its application programming interface (API) or through its graphical user interface (GUI). The GUI provides a straightforward two-dimensional (2D) rendering of a glycoprotein that allows for a quick visual inspection of the glycosylation state of all the sequons on a protein structure. Modeled glycans can be further refined by a genetic algorithm for removing clashes and sampling alternative conformations. Glycosylator can also identify specific three-dimensional (3D) glycans on a protein structure using a library of predefined templates. CONCLUSIONS: Glycosylator was used to generate models of glycosylated protein without steric clashes. Since the molecular topology is based on the CHARMM force field, new complex sugar moieties can be generated without modifying the internals of the code. Glycosylator provides more functionality for analyzing and modeling glycans than any other available software or webserver at present. Glycosylator will be a valuable tool for the glycoinformatics and biomolecular modeling communities.",2019 Oct 22,"['Lemmin, Thomas', 'Soto, Cinque']",BMC Bioinformatics,,,True
cbdc601a2f84e6e9749f437d5f25758f145c9137,PMC,Behavioral predictors of subsequent respiratory illness signs in dogs admitted to an animal shelter,http://dx.doi.org/10.1371/journal.pone.0224252,PMC6808433,31644583,CC BY,"Individual variability is evident in behavior and physiology of animals. Determining whether behavior at intake may predict subsequent illness in the animal shelter may influence the management of dogs housed at animal shelters and reduce overall disease. While normally associated with mild disease and low mortality rates, respiratory disease nevertheless poses significant challenges to the management of dogs in the stressful environment of animal shelters due to its highly infectious nature. Therefore, the aim of the study was to explore whether behavior at intake can predict subsequent occurrence and progression of upper respiratory disease in dogs at animal shelters. In a correlational study, 84 dogs were assessed throughout their stay at a city animal shelter. The dogs were subjected to a behavioral assessment, 1 min in-kennel behavioral observations across two observation periods, and the collection of urinary cortisol:creatinine (C:C) ratio. The occurrence and progression of upper respiratory disease was monitored through repeated clinical exams (rectal temperature and the occurrence of nasal and ocular discharge, and presence of coughing and sneezing). A basic PLS Path regression model revealed that time in the shelter (estimate = .53, p < .001), and sociability (estimate = .24, p < .001) and curiosity scores (estimate = .09, p = .026) were associated with increased illness. Activity and anxiety scores, however, were not associated with illness. Urinary C:C, taken on the first full day, did not predict subsequent illness when accounting for time. Limitations included attrition of dogs, a small percentage receiving vaccinations, and continuous and non-systematic rotation of dogs in the kennels. Understanding if behavior can predict subsequent illness may improve shelter management practices, and in turn, result in improved live-release outcomes.",2019 Oct 23,"['Protopopova, Alexandra', 'Hall, Nathaniel J.', 'Brown, Kelsea M.', 'Andrukonis, Allison S.', 'Hekman, Jessica P.']",PLoS One,,,True
686258462f76bc196e1b056ebbbb93a6f53c982e,PMC,IFN-Lambda 3 Mediates Antiviral Protection Against Porcine Epidemic Diarrhea Virus by Inducing a Distinct Antiviral Transcript Profile in Porcine Intestinal Epithelia,http://dx.doi.org/10.3389/fimmu.2019.02394,PMC6811514,31681286,CC BY,"Type III interferon-lambda (IFN-λ) plays a critical role against infection, particularly in mucosal infection in the respiratory and gastrointestinal tract. Our study and other previous studies have shown that porcine IFN-λ more efficiently curtails the infection of porcine epidemic diarrhea virus (PEDV) in the intestine epithelia than type I IFN, whereas IFN-λ3 exerts a more potent effect than IFN-λ1. However, the underlying mechanism remains elusive, and in particular, the transcriptional profile induced by IFN-λ3 has not been reported. Here, to resolve the mechanism responsible for the disparity between IFN-λ3 and type I IFN in anti-mucosal virus infection, we compared the transcription profiles induced by the two IFNs in porcine intestinal epithelial (IPEC-J2) cells by RNA-Seq. Our results showed that the pretreatment of IPEC-J2 cells with IFN-λ3 resulted in the differential expression of 983 genes. In contrast, IFN-α only modified the expression of 134 genes, and 110 of these genes were also observed in the response to IFN-λ3. A transcriptional enrichment analysis indicated that IFN-λ3 or IFN-α regulates multiple cellular processes and that IFN-λ3 activates more robust signaling pathways, particularly the antiviral Jak-STAT signaling pathway, than IFN-α. Furthermore, we verified the RNA-Seq results through an RT-qPCR analysis of IPEC-J2 cells and porcine enteroids. Moreover, transient expression of the porcine rsad2 and mx2 genes among the top 10 genes induced by IFN-λ3 significantly inhibited PEDV infection. Collectively, the data showed that IFN-λ3 induces a unique transcriptional profile that does not completely overlap with that induced by IFN-α and strongly elicits a set of genes responsible for the antiviral activity of IFN-λ3. These findings provide important knowledge regarding the elicited ISGs of type I and III IFNs in restricting porcine intestinal viral infection.",2019 Oct 17,"['Li, Liang', 'Xue, Mei', 'Fu, Fang', 'Yin, Lingdan', 'Feng, Li', 'Liu, Pinghuang']",Front Immunol,,,True
50c268968326f133eeacd3745e43a4226d867ce8,PMC,In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine,http://dx.doi.org/10.1038/s41598-019-51679-8,PMC6811573,31645650,CC BY,"Human papillomavirus (HPV) is the most common sexually transmitted infection in the world and the main cause of cervical cancer. Nowadays, the virus-like particles (VLPs) based on L1 proteins have been considered as the best candidate for vaccine development against HPV infections. Two commercial HPV (Gardasil and Cervarix) are available. These HPV VLP vaccines induce genotype-limited protection. The major impediments such as economic barriers especially gaps in financing obstructed the optimal delivery of vaccines in developing countries. Thus, many efforts are underway to develop the next generation of vaccines against other types of high-risk HPV. In this study, we developed DNA constructs (based on L1 and L2 genes) that were potentially immunogenic and highly conserved among the high-risk HPV types. The framework of analysis include (1) B-cell epitope mapping, (2) T-cell epitope mapping (i.e., CD4(+) and CD8(+) T cells), (3) allergenicity assessment, (4) tap transport and proteasomal cleavage, (5) population coverage, (6) global and template-based docking, and (7) data collection, analysis, and design of the L1 and L2 DNA constructs. Our data indicated the 8-epitope candidates for helper T-cell and CTL in L1 and L2 sequences. For the L1 and L2 constructs, combination of these peptides in a single universal vaccine could involve all world population by the rate of 95.55% and 96.33%, respectively. In vitro studies showed high expression rates of multiepitope L1 (~57.86%) and L2 (~68.42%) DNA constructs in HEK-293T cells. Moreover, in vivo studies indicated that the combination of L1 and L2 DNA constructs without any adjuvant or delivery system induced effective immune responses, and protected mice against C3 tumor cells (the percentage of tumor-free mice: ~66.67%). Thus, the designed L1 and L2 DNA constructs would represent promising applications for HPV vaccine development.",2019 Oct 23,"['Namvar, Ali', 'Bolhassani, Azam', 'Javadi, Gholamreza', 'Noormohammadi, Zahra']",Sci Rep,,,True
c112383dc204e7d830cc2094b2c5637c9d99b7d7,PMC,"Correlates of parasites and pseudoparasites in wolves (Canis lupus) across continents: A comparison among Yellowstone (USA), Abruzzo (IT) and Mercantour (FR) national parks",http://dx.doi.org/10.1016/j.ijppaw.2019.09.002,PMC6812024,31667082,CC BY,"Little is known about the impact of infectious diseases on large carnivores. We investigated factors structuring the helminth and protozoan infections of wolves (Canis lupus) by using coprological analyses. Faecal samples (n = 342) were analysed from 11 wolf packs belonging to three different geographical and ecological settings in Italy (Abruzzo, Lazio e Molise National Park, PNALM: 4 packs, 88 samples), in France (Mercantour National Park, PNM: 4 packs, 68 samples) and in the U.S.A. (Yellowstone National Park, YNP: 3 packs, 186 samples). Parasites were found in 29.4%–88.6% of the samples and parasite taxa ranged from four to ten in each study area. Taeniidae (Taenia/Echinococcus), Sarcocystis spp. and Toxascaris leonina were most common in faecal samples from YNP, whereas Capillaria spp., Taeniidae and Uncinaria stenocephala were predominant in PNALM. We used generalised linear mixed models to assess the relationship between parasite infection or the number of parasite taxa and selected ecological drivers across study areas. Significant effects illustrated the importance of the ecological factors such as occurrence of free-ranging dogs, diet composition and wolf density, as well as the ancestry of the wolf populations, in shaping parasite-wolf communities. Additional investigations are needed to elucidate the impact of parasitic infections on wolf populations, as well as the role of anthropogenic factors in facilitating parasitic diffusion to apex predators.",2019 Sep 12,"['Molnar, Barbara', 'Ciucci, Paolo', 'Mastrantonio, Gianluca', 'Betschart, Bruno']",Int J Parasitol Parasites Wildl,,,False
085d2f0a23b102cb7492350434746878eb834785,PMC,The respiratory virome and exacerbations in patients with chronic obstructive pulmonary disease,http://dx.doi.org/10.1371/journal.pone.0223952,PMC6812800,31647831,CC BY,"INTRODUCTION: Exacerbations are major contributors to morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), and respiratory bacterial and viral infections are an important trigger. However, using conventional diagnostic techniques, a causative agent is not always found. Metagenomic next-generation sequencing (mNGS) allows analysis of the complete virome, but has not yet been applied in COPD exacerbations. OBJECTIVES: To study the respiratory virome in nasopharyngeal samples during COPD exacerbations using mNGS. STUDY DESIGN: 88 nasopharyngeal swabs from 63 patients from the Bergen COPD Exacerbation Study (2006–2010) were analysed by mNGS and in-house qPCR for respiratory viruses. Both DNA and RNA were sequenced simultaneously using an Illumina library preparation protocol with in-house adaptations. RESULTS: By mNGS, 24/88 samples tested positive. Sensitivity and specificity, as compared with PCR, were 96% and 98% for diagnostic targets (23/24 and 1093/1120, respectively). Additional viral pathogens detected by mNGS were herpes simplex virus type 1 and coronavirus OC43. A positive correlation was found between Cq value and mNGS viral normalized species reads (log value) (p = 0.002). Patients with viral pathogens had lower percentages of bacteriophages (p<0.001). No correlation was found between viral reads and clinical markers. CONCLUSIONS: The mNGS protocol used was highly sensitive and specific for semi-quantitative detection of respiratory viruses. Excellent negative predictive value implicates the power of mNGS to exclude any pathogenic respiratory viral infectious cause in one test, with consequences for clinical decision making. Reduced abundance of bacteriophages in COPD patients with viral pathogens implicates skewing of the virome during infection, with potential consequences for the bacterial populations, during infection.",2019 Oct 24,"['van Rijn, Anneloes L.', 'van Boheemen, Sander', 'Sidorov, Igor', 'Carbo, Ellen C.', 'Pappas, Nikos', 'Mei, Hailiang', 'Feltkamp, Mariet', 'Aanerud, Marianne', 'Bakke, Per', 'Claas, Eric C. J.', 'Eagan, Tomas M.', 'Hiemstra, Pieter S.', 'Kroes, Aloys C. M.', 'de Vries, Jutte J. C.']",PLoS One,,,True
5292c918c5d12afda175d53424b40633166081bb,PMC,The Tudor SND1 protein is an m(6)A RNA reader essential for replication of Kaposi’s sarcoma-associated herpesvirus,http://dx.doi.org/10.7554/eLife.47261,PMC6812964,31647415,CC BY,"N(6)-methyladenosine (m(6)A) is the most abundant internal RNA modification of cellular mRNAs. m(6)A is recognised by YTH domain-containing proteins, which selectively bind to m(6)A-decorated RNAs regulating their turnover and translation. Using an m(6)A-modified hairpin present in the Kaposi’s sarcoma associated herpesvirus (KSHV) ORF50 RNA, we identified seven members from the ‘Royal family’ as putative m(6)A readers, including SND1. RIP-seq and eCLIP analysis characterised the SND1 binding profile transcriptome-wide, revealing SND1 as an m(6)A reader. We further demonstrate that the m(6)A modification of the ORF50 RNA is critical for SND1 binding, which in turn stabilises the ORF50 transcript. Importantly, SND1 depletion leads to inhibition of KSHV early gene expression showing that SND1 is essential for KSHV lytic replication. This work demonstrates that members of the ‘Royal family’ have m(6)A-reading ability, greatly increasing their epigenetic functions beyond protein methylation.",,"['Baquero-Perez, Belinda', 'Antanaviciute, Agne', 'Yonchev, Ivaylo D', 'Carr, Ian M', 'Wilson, Stuart A', 'Whitehouse, Adrian']",eLife.; 8:e47261,,,True
198bdc284caeafc6bbff6f925f36eec10d3d033c,PMC,Production of Defective Interfering Particles of Influenza A Virus in Parallel Continuous Cultures at Two Residence Times—Insights From qPCR Measurements and Viral Dynamics Modeling,http://dx.doi.org/10.3389/fbioe.2019.00275,PMC6813217,31681751,CC BY,"Defective interfering particles (DIPs) are a natural byproduct of influenza A virus (IAV) replication. DIPs interfere with the propagation and spread of infectious standard virus (STV), reduce virus yields by competing for viral and cellular resources, and induce antiviral responses. These properties open exciting possibilities for the development of DIP-based antivirals. Exploring options for cell culture-based DIP production, we have established a fully continuous cultivation process, where one bioreactor is used to grow cells that are fed to two bioreactors operated in parallel for virus production. This system allows head-to-head comparisons of STV and DIP replication dynamics over extended time periods. Cultivations were performed at two residence times (RT, 22 and 36 h) using MDCK suspension cells grown in a fully defined medium. For infection, we used a virus seed generated by reverse genetics containing STVs and a known DIP carrying a deletion in segment 1 (delS1(1)). Four days post infection, DIPs achieved maximum concentrations of 7.0·10(9) virions/mL and 8.4·10(9) virions/mL for RTs of 22 and 36 h, respectively. Furthermore, oscillations in virus titers with two to three maxima were found for DIP accumulation at 36 and 22 h RT, respectively. To complement the study, a basic mathematical model using simple kinetics and a reasonable number of parameters to describe DIP-propagation in continuous cultures was established. Upon fitting the model individually to each of the two data sets, oscillations in the viral dynamics and the cell population dynamics were described well. Modeling suggests that both STV inactivation and virus degradation have to be taken into account to achieve good agreement of simulations and experimental data for longer RTs. Together, the high DIP titers obtained, and the successful simulation of the experimental data showed that the combination of continuous bioreactors and mathematical models can enable studies regarding DIP dynamics over extended time periods and allow large scale manufacturing of DIP-based antivirals.",2019 Oct 18,"['Tapia, Felipe', 'Laske, Tanja', 'Wasik, Milena A.', 'Rammhold, Markus', 'Genzel, Yvonne', 'Reichl, Udo']",Front Bioeng Biotechnol,,,True
08ac78608c5be04ef1cff3fba52a3c7648bfa21a,PMC,Hematological and biochemical reference values of Asian house shrews (Suncus murinus) in Bangladesh,http://dx.doi.org/10.14202/vetworld.2019.1514-1518,PMC6813616,31749590,CC BY,"BACKGROUND AND AIM: Determining reference values for hematological and biochemical parameters of Asian house shrew (Suncus murinus) is important for wildlife research to protect human health in surrounding communities. This study aimed to establish the reference values for selected hematology and serum clinical chemistry analyses that may contribute to research on shrew in future. MATERIALS AND METHODS: Blood samples (n=51) were collected from shrews between July and December 2015, Bangladesh, to estimate the levels of hemoglobin (Hb), packed cell volume (PCV), total leukocyte count (TLC), total erythrocyte count (TEC), lymphocyte, monocyte, neutrophil, eosinophil, basophil, calcium, phosphorus (P), sodium (Na), chloride (Cl), urea, glucose, total protein (TP), creatinine, and alanine transaminase (ALT). RESULTS: Although the values did not differ significantly among sexes, age was found to be a significant factor. Hb, PCV, TEC, glucose, and P were higher in males; eosinophil, Na, Cl, TP, and ALT were higher among females. Adults had significantly greater urea and glucose (p<0.05) while juveniles had insignificantly higher values for TLC, PCV, neutrophil, P, and TP. CONCLUSION: This study provides the first reference values for this species in Bangladesh and can be used to guide wildlife research studies.",2019 Sep,"['Rahman, Md. Kaisar', 'Islam, Shariful', 'Rahman, Mizanur', 'Ferdous, Jinnat', 'Akter, Sazeda', 'Rahaman, Md. Mustafizur', 'Hossain, Mohammad Alamgir', 'Hassan, Mohammad Mahmudul', 'Islam, Ariful']",Vet World,,,True
b42f394d5ea15733d96063ffabef231a98ce5429,PMC,A structure-based rationale for sialic acid independent host-cell entry of Sosuga virus,http://dx.doi.org/10.1073/pnas.1906717116,PMC6815108,31591233,CC BY,"The bat-borne paramyxovirus, Sosuga virus (SosV), is one of many paramyxoviruses recently identified and classified within the newly established genus Pararubulavirus, family Paramyxoviridae. The envelope surface of SosV presents a receptor-binding protein (RBP), SosV-RBP, which facilitates host-cell attachment and entry. Unlike closely related hemagglutinin neuraminidase RBPs from other genera of the Paramyxoviridae, SosV-RBP and other pararubulavirus RBPs lack many of the stringently conserved residues required for sialic acid recognition and hydrolysis. We determined the crystal structure of the globular head region of SosV-RBP, revealing that while the glycoprotein presents a classical paramyxoviral six-bladed β-propeller fold and structurally classifies in close proximity to paramyxoviral RBPs with hemagglutinin-neuraminidase (HN) functionality, it presents a receptor-binding face incongruent with sialic acid recognition. Hemadsorption and neuraminidase activity analysis confirms the limited capacity of SosV-RBP to interact with sialic acid in vitro and indicates that SosV-RBP undergoes a nonclassical route of host-cell entry. The close overall structural conservation of SosV-RBP with other classical HN RBPs supports a model by which pararubulaviruses only recently diverged from sialic acid binding functionality.",2019 Oct 22,"['Stelfox, Alice J.', 'Bowden, Thomas A.']",Proc Natl Acad Sci U S A,,,True
eddb4ccfc3420d4cdaafabbc081bec8758930e53,PMC,A structure-based rationale for sialic acid independent host-cell entry of Sosuga virus,http://dx.doi.org/10.1073/pnas.1906717116,PMC6815108,31591233,CC BY,"The bat-borne paramyxovirus, Sosuga virus (SosV), is one of many paramyxoviruses recently identified and classified within the newly established genus Pararubulavirus, family Paramyxoviridae. The envelope surface of SosV presents a receptor-binding protein (RBP), SosV-RBP, which facilitates host-cell attachment and entry. Unlike closely related hemagglutinin neuraminidase RBPs from other genera of the Paramyxoviridae, SosV-RBP and other pararubulavirus RBPs lack many of the stringently conserved residues required for sialic acid recognition and hydrolysis. We determined the crystal structure of the globular head region of SosV-RBP, revealing that while the glycoprotein presents a classical paramyxoviral six-bladed β-propeller fold and structurally classifies in close proximity to paramyxoviral RBPs with hemagglutinin-neuraminidase (HN) functionality, it presents a receptor-binding face incongruent with sialic acid recognition. Hemadsorption and neuraminidase activity analysis confirms the limited capacity of SosV-RBP to interact with sialic acid in vitro and indicates that SosV-RBP undergoes a nonclassical route of host-cell entry. The close overall structural conservation of SosV-RBP with other classical HN RBPs supports a model by which pararubulaviruses only recently diverged from sialic acid binding functionality.",2019 Oct 22,"['Stelfox, Alice J.', 'Bowden, Thomas A.']",Proc Natl Acad Sci U S A,,,True
4631d1a1d9384ce4aa9d96d6695417357855ce84,PMC,Population-based surveys and interventions for mental health literacy in China during 1997–2018: a scoping review,http://dx.doi.org/10.1186/s12888-019-2307-0,PMC6815452,31655552,CC BY,"BACKGROUND: This scoping review maps population-based surveys and mental health literacy (MHL) interventions undertaken in China during 1997–2018 in order to identify research gaps. METHOD: Following Arksey and O’Malley’s framework for a scoping review, five English databases (Medline, PsycINFO, Cochrane library, Web of Science and CINAHL) and two Chinese ones (CNKI and WanFang) were systematically searched, identifying both reports of surveys and evaluation of interventions from Jan 1997 to Oct 2018. RESULTS: MHL research has developed rapidly in China in terms of numbers of studies and geographic coverage over the past two decades. There were 350 peer-reviewed publications included in this review, covering diverse settings and participants. Of these publications, 313 (89.4%) were published in Chinese-language journals and 37 in English-language journals; 303 (86.6%) reported on survey findings and 47 reported on the evaluation of MHL interventions. MHL research in China has mainly focused on the assessment of mental health-related knowledge and beliefs. Much less attention has been given to developing and evaluating relevant interventions. MHL related to general mental health and suicide were most commonly studied, with less focus on specific disorders, although some studies covered depression, psychosis and anxiety disorders. The majority of MHL tools utilized in the studies reported in this review were developed in China (n = 97, 80.2% ) and almost half of these studies (57.8%) did not provide enough details concerning psychometrics. CONCLUSIONS: More interventions targeting the general public and aiming to improve MHL and promote behaviour change, are needed in China. These should be evaluated with high-quality study designs, such as randomised controlled trials. Proper validation of tools used for measuring MHL should also be addressed in future studies.",2019 Oct 26,"['Lu, Shurong', 'Oldenburg, Brian', 'Li, Wenjing', 'He, Yanling', 'Reavley, Nicola']",BMC Psychiatry,,,True
ca34ce0dd508d0f8777cc259e1b2fd4a58b73491,PMC,Contamination of hospital surfaces with respiratory pathogens in Bangladesh,http://dx.doi.org/10.1371/journal.pone.0224065,PMC6816543,31658279,CC0,"With limited infection control practices in overcrowded Bangladeshi hospitals, surfaces may play an important role in the transmission of respiratory pathogens in hospital wards and pose a serious risk of infection for patients, health care workers, caregivers and visitors. In this study, we aimed to identify if surfaces near hospitalized patients with respiratory infections were contaminated with respiratory pathogens and to identify which surfaces were most commonly contaminated. Between September-November 2013, we collected respiratory (nasopharyngeal and oropharyngeal) swabs from patients hospitalized with respiratory illness in adult medicine and paediatric medicine wards at two public tertiary care hospitals in Bangladesh. We collected surface swabs from up to five surfaces near each case-patient including: the wall, bed rail, bed sheet, clinical file, and multipurpose towel used for care giving purposes. We tested swabs using real-time multiplex PCR for 19 viral and 12 bacterial pathogens. Case-patients with at least one pathogen detected had corresponding surface swabs tested for those same pathogens. Of 104 patients tested, 79 had a laboratory-confirmed respiratory pathogen. Of the 287 swabs collected from surfaces near these patients, 133 (46%) had evidence of contamination with at least one pathogen. The most commonly contaminated surfaces were the bed sheet and the towel. Sixty-two percent of patients with a laboratory-confirmed respiratory pathgen (49/79) had detectable viral or bacterial nucleic acid on at least one surface. Klebsiella pneumoniae was the most frequently detected pathogen on both respiratory swabs (32%, 33/104) and on surfaces near patients positive for this organism (97%, 32/33). Surfaces near patients hospitalized with respiratory infections were frequently contaminated by pathogens, with Klebsiella pneumoniae being most common, highlighting the potential for transmission of respiratory pathogens via surfaces. Efforts to introduce routine cleaning in wards may be a feasible strategy to improve infection control, given that severe space constraints prohibit cohorting patients with respiratory illness.",2019 Oct 28,"['Hassan, Md. Zakiul', 'Sturm-Ramirez, Katharine', 'Rahman, Mohammad Ziaur', 'Hossain, Kamal', 'Aleem, Mohammad Abdul', 'Bhuiyan, Mejbah Uddin', 'Islam, Md. Muzahidul', 'Rahman, Mahmudur', 'Gurley, Emily S.']",PLoS One,,,True
5c313555924b8f0f82f082673f42b56ef736c20a,PMC,Evidence-Based Process for Prioritizing Positive Behaviors for Promotion: Zika Prevention in Latin America and the Caribbean and Applicability to Future Health Emergency Responses,http://dx.doi.org/10.9745/GHSP-D-19-00188,PMC6816817,31558597,CC BY,"Since the 2015 Zika outbreak in Latin America and the Caribbean, a plethora of behavior change messages have been promoted to reduce Zika transmission. One year after the United States Agency for International Development (USAID) initiated its Zika response, more than 30 variants of preventive behaviors were being promoted. This situation challenged social and behavior change (SBC) programming efforts that require a coordinated response and agreed upon set of focus behaviors to be effective. To support USAID implementing partners in harmonizing prevention efforts to reduce Zika infection, we developed an evidence-based process to identify behaviors with the highest potential to reduce Zika infection and transmission. We compiled a full list of behaviors and selected the most promising for a full evidence review. The review included systematic keyword searches on Google Scholar, extraction of all relevant published articles on Aedes-borne diseases between 2012 and 2018, review of seminal papers, and review of gray literature. We examined articles to determine each behavior's potential effectiveness in preventing Zika transmission or reducing the Aedes aegypti population. We also developed assessment criteria to delineate the ease with which the target population could adopt each behavior, including: (1) required frequency; (2) feasibility of the behavior; and (3) accessibility and cost of the necessary materials in the setting. These behaviors were refined through a consensus-building process with USAID's Zika implementing partners, considering contextual factors. The resulting 7 evidence-based preventive behaviors have high potential to strengthen SBC programming's impact in USAID's Zika response: (1) apply mosquito repellent, (2) use condoms during pregnancy, (3) remove standing water, (4) cover water storage containers, (5) clean/remove mosquito eggs from water containers, (6) seek antenatal care, and (7) seek family planning counseling. This case study documents a flexible process that can be adapted to inform the prioritization of behaviors when there is limited evidence available, as during many emergency responses.",2019 Sep 23,"['Pinchoff, Jessie', 'Serino, Arianna', 'Merritt, Alice Payne', 'Hunter, Gabrielle', 'Silva, Martha', 'Parikh, Priya', 'Hewett, Paul C.']",Glob Health Sci Pract,,,True
52a61f0348480cb8c5b29d22307b8a1449e64f0e,PMC,A Minimally Replicative Vaccine Protects Vaccinated Piglets Against Challenge With the Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.3389/fvets.2019.00347,PMC6817509,31696121,CC BY,"Porcine epidemic diarrhea virus (PEDV), is an economically important enteric coronavirus, with over a 90% mortality rate in neonatal piglets. The virus emerged in the US in 2013, resulting in severe production losses. Effective vaccine development against PEDV is a challenge. Inactivated vaccines are of questionable efficacy. Attenuated vaccines, while more effective, require a relatively long lead development time, are associated with safety concerns and are also unable to prevent new field outbreaks. To combine the safety and efficacy advantages of inactivated and attenuated PEDV vaccines, respectively, in this study, we tested the hypothesis that subjecting PEDV virions to heat treatment at 44°C for 10 min to reversibly unfold structural proteins, followed by exposure to RNAse to fragment the genome, would result in a vaccine preparation with intact viral structure/antigenicity but highly diminished replicative abilities. We expected the vaccine to be both safe and effective in a piglet challenge model. Following the heat and RNAse treatment, PEDV virions had an intact electron microscopic ultrastructure and were amplified only in the 3rd passage in Vero cells, indicating that diminished replication was achieved in vitro. Strong PEDV spike-protein specific and virus neutralizing antibody responses were elicited in vaccinated piglets. Upon challenge, all vaccinated pigs were protected against fecal viral shedding and intestinal pathology, while the unvaccinated controls were not. The vaccine virus was not detected in the fecal matter of vaccinated pigs prior to challenge; nor did they develop intestinal lesions. Thus, the described approach has significant promise in improving current approaches for PEDV immunization.",2019 Oct 22,"['Singh, Gagandeep', 'Singh, Pankaj', 'Pillatzki, Angela', 'Nelson, Eric', 'Webb, Brett', 'Dillberger-Lawson, Steven', 'Ramamoorthy, Sheela']",Front Vet Sci,,,True
2f314a77ea26734587af46d6ed32345b0160760e,PMC,Dudleya brittonii extract promotes survival rate and M2-like metabolic change in porcine 3D4/31 alveolar macrophages,http://dx.doi.org/10.5713/ajas.19.0251,PMC6817779,31208190,CC BY,"OBJECTIVE: Although alveolar macrophages play a key role in the respiratory immunity of livestock, studies on the mechanism of differentiation and survival of alveolar macrophages are lacking. Therefore, we undertook to investigate changes in the lipid metabolism and survival rate, using 3D4/31 macrophages and Dudleya brittonii which has been used as a traditional asthma treatment. METHODS: 3D4/31 macrophages were used as the in vitro porcine alveolar macrophages model. The cells were activated by exposure to phorbol 12-myristate 13-acetate (PMA). Dudleya brittonii extraction was performed with distilled water. For evaluating the cell survival rate, we performed the water-soluble tetrazolium salt cell viability assay and growth curve analysis. To confirm cell death, cell cycle and intracellular reactive oxygen species (ROS) levels were measured using flow cytometric analysis by applying fluorescence dye dichlorofluorescein diacetate and propidium iodide. Furthermore, we also evaluated cellular lipid accumulation with oil red O staining, and fatty acid synthesis related genes expression levels using quantitative polymerase chain reaction (qPCR) with SYBR green dye. Glycolysis, fatty acid oxidation, and tricarboxylic acid (TCA) cycle related gene expression levels were measured using qPCR after exposure to Dudleya brittonii extract (DB) for 12 h. RESULTS: The ROS production and cell death were induced by PMA treatment, and exposure to DB reduced the PMA induced downregulation of cell survival. The PMA and DB treatments upregulated the lipid accumulation, with corresponding increase in the acetyl-CoA carboxylase alpha, fatty acid synthase mRNA expressions. DB-PMA co-treatment reduced the glycolysis genes expression, but increased the expressions of fatty acid oxidation and TCA cycle genes. CONCLUSION: This study provides new insights and directions for further research relating to the immunity of porcine respiratory system, by employing a model based on alveolar macrophages and natural materials.",2019 Nov 27,"['Kim, Hyungkuen', 'Jeon, Eek Hyung', 'Park, Byung-Chul', 'Kim, Sung-Jo']",Asian-Australas J Anim Sci,,,True
950476a6a916a066fb215b34bdf68f4ff79f2928,PMC,Engineered amphiphilic peptides enable delivery of proteins and CRISPR-associated nucleases to airway epithelia,http://dx.doi.org/10.1038/s41467-019-12922-y,PMC6817825,31659165,CC BY,"The delivery of biologic cargoes to airway epithelial cells is challenging due to the formidable barriers imposed by its specialized and differentiated cells. Among cargoes, recombinant proteins offer therapeutic promise but the lack of effective delivery methods limits their development. Here, we achieve protein and SpCas9 or AsCas12a ribonucleoprotein (RNP) delivery to cultured human well-differentiated airway epithelial cells and mouse lungs with engineered amphiphilic peptides. These shuttle peptides, non-covalently combined with GFP protein or CRISPR-associated nuclease (Cas) RNP, allow rapid entry into cultured human ciliated and non-ciliated epithelial cells and mouse airway epithelia. Instillation of shuttle peptides combined with SpCas9 or AsCas12a RNP achieves editing of loxP sites in airway epithelia of ROSA(mT/mG) mice. We observe no evidence of short-term toxicity with a widespread distribution restricted to the respiratory tract. This peptide-based technology advances potential therapeutic avenues for protein and Cas RNP delivery to refractory airway epithelial cells.",2019 Oct 28,"['Krishnamurthy, Sateesh', 'Wohlford-Lenane, Christine', 'Kandimalla, Suhas', 'Sartre, Gilles', 'Meyerholz, David K.', 'Théberge, Vanessa', 'Hallée, Stéphanie', 'Duperré, Anne-Marie', 'Del’Guidice, Thomas', 'Lepetit-Stoffaes, Jean-Pascal', 'Barbeau, Xavier', 'Guay, David', 'McCray, Paul B.']",Nat Commun,,,False
1cdf5f7fb665c7d9efaf8562af501d3b3bdd9273,PMC,Engineered amphiphilic peptides enable delivery of proteins and CRISPR-associated nucleases to airway epithelia,http://dx.doi.org/10.1038/s41467-019-12922-y,PMC6817825,31659165,CC BY,"The delivery of biologic cargoes to airway epithelial cells is challenging due to the formidable barriers imposed by its specialized and differentiated cells. Among cargoes, recombinant proteins offer therapeutic promise but the lack of effective delivery methods limits their development. Here, we achieve protein and SpCas9 or AsCas12a ribonucleoprotein (RNP) delivery to cultured human well-differentiated airway epithelial cells and mouse lungs with engineered amphiphilic peptides. These shuttle peptides, non-covalently combined with GFP protein or CRISPR-associated nuclease (Cas) RNP, allow rapid entry into cultured human ciliated and non-ciliated epithelial cells and mouse airway epithelia. Instillation of shuttle peptides combined with SpCas9 or AsCas12a RNP achieves editing of loxP sites in airway epithelia of ROSA(mT/mG) mice. We observe no evidence of short-term toxicity with a widespread distribution restricted to the respiratory tract. This peptide-based technology advances potential therapeutic avenues for protein and Cas RNP delivery to refractory airway epithelial cells.",2019 Oct 28,"['Krishnamurthy, Sateesh', 'Wohlford-Lenane, Christine', 'Kandimalla, Suhas', 'Sartre, Gilles', 'Meyerholz, David K.', 'Théberge, Vanessa', 'Hallée, Stéphanie', 'Duperré, Anne-Marie', 'Del’Guidice, Thomas', 'Lepetit-Stoffaes, Jean-Pascal', 'Barbeau, Xavier', 'Guay, David', 'McCray, Paul B.']",Nat Commun,,,True
f04518627b8397d11241046b09b3925ce3cd31ac,PMC,Engineered amphiphilic peptides enable delivery of proteins and CRISPR-associated nucleases to airway epithelia,http://dx.doi.org/10.1038/s41467-019-12922-y,PMC6817825,31659165,CC BY,"The delivery of biologic cargoes to airway epithelial cells is challenging due to the formidable barriers imposed by its specialized and differentiated cells. Among cargoes, recombinant proteins offer therapeutic promise but the lack of effective delivery methods limits their development. Here, we achieve protein and SpCas9 or AsCas12a ribonucleoprotein (RNP) delivery to cultured human well-differentiated airway epithelial cells and mouse lungs with engineered amphiphilic peptides. These shuttle peptides, non-covalently combined with GFP protein or CRISPR-associated nuclease (Cas) RNP, allow rapid entry into cultured human ciliated and non-ciliated epithelial cells and mouse airway epithelia. Instillation of shuttle peptides combined with SpCas9 or AsCas12a RNP achieves editing of loxP sites in airway epithelia of ROSA(mT/mG) mice. We observe no evidence of short-term toxicity with a widespread distribution restricted to the respiratory tract. This peptide-based technology advances potential therapeutic avenues for protein and Cas RNP delivery to refractory airway epithelial cells.",2019 Oct 28,"['Krishnamurthy, Sateesh', 'Wohlford-Lenane, Christine', 'Kandimalla, Suhas', 'Sartre, Gilles', 'Meyerholz, David K.', 'Théberge, Vanessa', 'Hallée, Stéphanie', 'Duperré, Anne-Marie', 'Del’Guidice, Thomas', 'Lepetit-Stoffaes, Jean-Pascal', 'Barbeau, Xavier', 'Guay, David', 'McCray, Paul B.']",Nat Commun,,,True
33fbcefc12a3f06bf2e20b88ac1b69d481746250,PMC,Serological evidence of MERS-CoV and HKU8-related CoV co-infection in Kenyan camels,http://dx.doi.org/10.1080/22221751.2019.1679610,PMC6818114,31645223,CC BY,"Dromedary camels are important reservoir hosts of various coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV) that cause human infections. CoV genomes regularly undergo recombination during infection as observed in bat SARS-related CoVs. Here we report for the first time that only a small proportion of MERS-CoV receptor-binding domain positive (RBD) of spike protein positive camel sera in Kenya were also seropositive to MERS-CoV nucleocapsid (NP). In contrast, many of them contain antibodies against bat HKU8-related (HKU8r)-CoVs. Among 584 camel samples that were positive against MERS-CoV RBD, we found only 0.48 (8.22%) samples were also positive for NP. Furthermore, we found bat HKU8r-CoV NP antibody in 73 (12.5%) of the MERS-CoV RBD positive and NP negative samples, yet found only 3 (0.43%) of the HKU8r-CoV S1 antibody in the same samples. These findings may indicate co-infection with MERS-CoV and a HKU8r-CoV in camels. It may also raise the possibility of the circulation of a recombinant coronavirus virus with the spike of MERS-CoV and the NP of a HKU8r-CoV in Kenya. We failed to find molecular evidence of an HKU8r-CoV or a putative recombinant virus. Our findings should alert other investigators to look for molecular evidence of HKU8r-CoV or recombinants.",2019 Oct 24,"['Zhang, Wei', 'Zheng, Xiao-Shuang', 'Agwanda, Bernard', 'Ommeh, Sheila', 'Zhao, Kai', 'Lichoti, Jacqueline', 'Wang, Ning', 'Chen, Jing', 'Li, Bei', 'Yang, Xing-Lou', 'Mani, Shailendra', 'Ngeiywa, Kisa-Juma', 'Zhu, Yan', 'Hu, Ben', 'Onyuok, Samson Omondi', 'Yan, Bing', 'Anderson, Danielle E.', 'Wang, Lin-Fa', 'Zhou, Peng', 'Shi, Zheng-Li']",Emerg Microbes Infect,,,True
61baa9b1ae842b28e3e7aa90a3e8034d96ba9aa9,PMC,The Nsp12-coding region of type 2 PRRSV is required for viral subgenomic mRNA synthesis,http://dx.doi.org/10.1080/22221751.2019.1679010,PMC6818116,31631782,CC BY,"As one of many nonstructural proteins of porcine reproductive and respiratory syndrome virus (PRRSV), nonstructural protein 12 (Nsp12) has received relatively little attention, and its role in virus replication, if any, is essentially unknown. By the application of reverse genetic manipulation of an infectious PRRSV clone, the current study is the first to demonstrate that Nsp12 is a key component of PRRSV replication. In addition, the biochemical properties of Nsp12 were evaluated, revealing that Nsp12 forms dimers when exposed to oxidative conditions. Furthermore, we systemically analyzed the function of Nsp12 in PRRSV RNA synthesis using a strand-specific PCR method. To our surprise, Nsp12 was not found to be involved in minus-strand genomic RNA (-gRNA) synthesis; importantly, our results indicate that Nsp12 is involved in the synthesis of both plus- and minus-strand subgenomic mRNAs (+sgmRNA and -sgmRNA). Finally, we found that the combination of cysteine 35 and cysteine 79 in Nsp12 is required for sgmRNA synthesis. To our knowledge, we are the first to report the biological role of Nsp12 in the PRRSV lifecycle, and we conclude that Nsp12 is involved in the synthesis of both + sgRNA and -sgRNA.",2019 Oct 21,"['Wang, Tong-Yun', 'Fang, Qiong-Qiong', 'Cong, Feng', 'Liu, Yong-Gang', 'Wang, Hai-Ming', 'Zhang, Hong-Liang', 'Tian, Zhi-Jun', 'Tang, Yan-Dong', 'Cai, Xue-Hui']",Emerg Microbes Infect,,,True
19df6a2ae9a9070dd15404465eed98ad222b27f0,PMC,"GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus",http://dx.doi.org/10.1080/22221751.2019.1677446,PMC6818130,31631785,CC BY,"Interferons (IFNs) control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication. We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses. Specifically, we demonstrated that GILT was constitutively expressed in lung epithelial cells and fibroblasts and its expression could be further induced by type II interferon. While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins. Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry. We also found that the induction of GILT expression reduced the level and activity of cathepsin L, which is required for the entry of these RNA viruses in lysosomes. Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.",2019 Oct 21,"['Chen, Danying', 'Hou, Zhifei', 'Jiang, Dong', 'Zheng, Mei', 'Li, Guoli', 'Zhang, Yue', 'Li, Rui', 'Lin, Hanxin', 'Chang, Jinhong', 'Zeng, Hui', 'Guo, Ju-Tao', 'Zhao, Xuesen']",Emerg Microbes Infect,,,True
3819c9d30c75527e915470a797c69fa83934fa06,PMC,P200 family protein IFI204 negatively regulates type I interferon responses by targeting IRF7 in nucleus,http://dx.doi.org/10.1371/journal.ppat.1008079,PMC6818788,31603949,CC BY,"Interferon-inducible p200 family protein IFI204 was reported to be involved in DNA sensing, and subsequently induces the production of type I interferons and proinflammatory mediators. However, its function in the regulation of antiviral innate immune signaling pathway remains unclear. Here we reported a novel role of IFI204 that specifically inhibits the IRF7-mediated type I interferons response during viral infection. IFI204 and other p200 family proteins are highly expressed in mouse hepatitis coronavirus-infected bone marrow-derived dendritic cells. The abundant IFI204 could significantly interact with IRF7 in nucleus by its HIN domain and prevent the binding of IRF7 with its corresponding promoter. Moreover, other p200 family proteins that possess HIN domain could also inhibit the IRF7-mediated type I interferons. These results reveal that, besides the positive regulation function in type I interferon response at the early stage of DNA virus infection, the interferon-inducible p200 family proteins such as IFI204 could also negatively regulate the IRF7-mediated type I interferon response after RNA virus infection to avoid unnecessary host damage from hyper-inflammatory responses.",2019 Oct 11,"['Cao, Liu', 'Ji, Yanxi', 'Zeng, Lanyi', 'Liu, Qianyun', 'Zhang, Zhen', 'Guo, Shuting', 'Guo, Xiaolong', 'Tong, Yongjia', 'Zhao, Xiaolu', 'Li, Chun-Mei', 'Chen, Yu', 'Guo, Deyin']",PLoS Pathog,,,True
40c15d7dfd277d6c181783e56c9c996664c2ba5b,PMC,Preparing intensive care for the next pandemic influenza,http://dx.doi.org/10.1186/s13054-019-2616-1,PMC6819413,31665057,CC BY,"Few viruses have shaped the course of human history more than influenza viruses. A century since the 1918–1919 Spanish influenza pandemic—the largest and deadliest influenza pandemic in recorded history—we have learned much about pandemic influenza and the origins of antigenic drift among influenza A viruses. Despite this knowledge, we remain largely underprepared for when the next major pandemic occurs. While emergency departments are likely to care for the first cases of pandemic influenza, intensive care units (ICUs) will certainly see the sickest and will likely have the most complex issues regarding resource allocation. Intensivists must therefore be prepared for the next pandemic influenza virus. Preparation requires multiple steps, including careful surveillance for new pandemics, a scalable response system to respond to surge capacity, vaccine production mechanisms, coordinated communication strategies, and stream-lined research plans for timely initiation during a pandemic. Conservative models of a large-scale influenza pandemic predict more than 170% utilization of ICU-level resources. When faced with pandemic influenza, ICUs must have a strategy for resource allocation as strain increases on the system. There are several current threats, including avian influenza A(H5N1) and A(H7N9) viruses. As humans continue to live in closer proximity to each other, travel more extensively, and interact with greater numbers of birds and livestock, the risk of emergence of the next pandemic influenza virus mounts. Now is the time to prepare and coordinate local, national, and global efforts.",2019 Oct 30,"['Kain, Taylor', 'Fowler, Robert']",Crit Care,,,True
0f5a26ea1de2f221c64ee9dc06fa4a9b41bbb1a7,PMC,Macrophage migration inhibitory factor of Syrian golden hamster shares structural and functional similarity with human counterpart and promotes pancreatic cancer,http://dx.doi.org/10.1038/s41598-019-51947-7,PMC6820718,31664114,CC BY,"Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that increasingly is being studied in cancers and inflammatory diseases. Though murine models have been instrumental in understanding the functional role of MIF in different pathological conditions, the information obtained from these models is biased towards a specific species. In experimental science, results obtained from multiple clinically relevant animal models always provide convincing data that might recapitulate in humans. Syrian golden hamster (Mesocricetus auratus), is a clinically relevant animal model for multiple human diseases. Hence, the major objectives of this study were to characterize the structure and function of Mesocricetus auratus MIF (MaMIF) and finally evaluate its effect on pancreatic tumor growth in vivo. Initially, the recombinant MaMIF was cloned, expressed and purified in a bacterial expression system. The MaMIF primary sequence, biochemical properties, and crystal structure analysis showed greater similarity with human MIF. The crystal structure of MaMIF illustrates that it forms a homotrimer as known in human and mouse. However, MaMIF exhibits some minor structural variations when compared to human and mouse MIF. The in vitro functional studies show that MaMIF has tautomerase activity and enhances activation and migration of hamster peripheral blood mononuclear cells (PBMCs). Interestingly, injection of MaMIF into HapT1 pancreatic tumor-bearing hamsters significantly enhanced the tumor growth and tumor-associated angiogenesis. Together, the current study shows a structural and functional similarity between the hamster and human MIF. Moreover, it has demonstrated that a high level of circulating MIF originating from non-tumor cells might also promote pancreatic tumor growth in vivo.",2019 Oct 29,"['Suresh, Voddu', 'Sundaram, Rajivgandhi', 'Dash, Pujarini', 'Sabat, Surendra Chandra', 'Mohapatra, Debasish', 'Mohanty, Sneha', 'Vasudevan, Dileep', 'Senapati, Shantibhusan']",Sci Rep,,,False
8a2a859f5920d1a81d0ab2e619f00f729331fedc,PMC,Macrophage migration inhibitory factor of Syrian golden hamster shares structural and functional similarity with human counterpart and promotes pancreatic cancer,http://dx.doi.org/10.1038/s41598-019-51947-7,PMC6820718,31664114,CC BY,"Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that increasingly is being studied in cancers and inflammatory diseases. Though murine models have been instrumental in understanding the functional role of MIF in different pathological conditions, the information obtained from these models is biased towards a specific species. In experimental science, results obtained from multiple clinically relevant animal models always provide convincing data that might recapitulate in humans. Syrian golden hamster (Mesocricetus auratus), is a clinically relevant animal model for multiple human diseases. Hence, the major objectives of this study were to characterize the structure and function of Mesocricetus auratus MIF (MaMIF) and finally evaluate its effect on pancreatic tumor growth in vivo. Initially, the recombinant MaMIF was cloned, expressed and purified in a bacterial expression system. The MaMIF primary sequence, biochemical properties, and crystal structure analysis showed greater similarity with human MIF. The crystal structure of MaMIF illustrates that it forms a homotrimer as known in human and mouse. However, MaMIF exhibits some minor structural variations when compared to human and mouse MIF. The in vitro functional studies show that MaMIF has tautomerase activity and enhances activation and migration of hamster peripheral blood mononuclear cells (PBMCs). Interestingly, injection of MaMIF into HapT1 pancreatic tumor-bearing hamsters significantly enhanced the tumor growth and tumor-associated angiogenesis. Together, the current study shows a structural and functional similarity between the hamster and human MIF. Moreover, it has demonstrated that a high level of circulating MIF originating from non-tumor cells might also promote pancreatic tumor growth in vivo.",2019 Oct 29,"['Suresh, Voddu', 'Sundaram, Rajivgandhi', 'Dash, Pujarini', 'Sabat, Surendra Chandra', 'Mohapatra, Debasish', 'Mohanty, Sneha', 'Vasudevan, Dileep', 'Senapati, Shantibhusan']",Sci Rep,,,True
7d9e398e0de06f3fc877f3d67489e798b7c31c20,PMC,Pertussis hospitalizations among term and preterm infants: clinical course and vaccine effectiveness,http://dx.doi.org/10.1186/s12879-019-4563-5,PMC6820906,31664950,CC BY,"BACKGROUND: Pertussis causes severe disease in young unvaccinated infants, with preterms potentially at highest risk. We studied pertussis in hospitalized infants as related to gestational age (GA) and vaccination history. METHODS: Medical record data of 0-2y old patients hospitalized for pertussis during 2005–2014 were linked to vaccination data. Multivariable logistic regression was used to study the association between GA and vaccination history on the clinical disease course. We compared vaccine effectiveness (VE) against hospitalization for pertussis between term and preterm infants (i.e., <37w GA) using the screening method as developed by Farrington. RESULTS: Of 1187 records, medical data from 676 were retrieved. Of these, 12% concerned preterms, whereas they are 8% of Dutch birth cohorts. Median age at admission was 3 m for preterms and 2 m for terms (p < 0.001). Preterms more often had received pertussis vaccination (62% vs 44%; p = 0.01) and more often had coinfections (37% vs 21%; p = 0.01). Preterms tended more often to have complications, to require artificial respiration or to need admittance to the intensive care unit (ICU). Preterms had longer ICU stays (15d vs 9d; p = 0.004). Vaccinated preterms and terms had a lower median length of hospital stay and lower crude risks of apneas and the need for artificial respiration, additional oxygen, and ICU admittance than those not vaccinated. After adjustment for presence of coinfections and age at admittance, these differences were not significant, except the lower need of oxygen treatment in vaccinated terms. Effectiveness of the first vaccination against pertussis hospitalizations was 95% (95% CI 93–96%) and 73% (95% CI 20–91%) in terms and preterms, respectively. Effectiveness of the second dose of the primary vaccination series was comparable in both groups (86 and 99%, respectively). CONCLUSIONS: Infants hospitalized for pertussis suffer from severe disease. Preterms were overrepresented, with higher need for intensive treatment and less VE of first vaccination. These findings stress the need for alternative prevention, in particular prenatal vaccination of mothers, to reduce pertussis in both groups.",2019 Oct 29,"['van der Maas, Nicoline A. T.', 'Sanders, Elisabeth A. M.', 'Versteegh, Florens G. A.', 'Baauw, Albertine', 'Westerhof, Anneke', 'de Melker, Hester E.']",BMC Infect Dis,,,True
c121bff36744aaaa59d19e21bb04b7f776cbeb42,PMC,Development of a Potent and Protective Germline-Like Antibody Lineage Against Zika Virus in a Convalescent Human,http://dx.doi.org/10.3389/fimmu.2019.02424,PMC6821881,31708914,CC BY,"Zika virus (ZIKV) specific neutralizing antibodies hold great promise for antibody-based interventions and vaccine design against ZIKV infection. However, their development in infected patients remains unclear. Here, we applied next-generation sequencing (NGS) to probe the dynamic development of a potent and protective ZIKV E DIII-specific antibody ZK2B10 isolated from a ZIKV convalescent individual. The unbiased repertoire analysis showed dramatic changes in the usage of antibody variable region germline genes. However, lineage tracing of ZK2B10 revealed limited somatic hypermutation and transient expansion during the 12 months following the onset of symptoms. The NGS-derived, germline-like ZK2B10 somatic variants neutralized ZIKV potently and protected mice from lethal challenge of ZIKV without detectable cross-reactivity with Dengue virus (DENV). Site-directed mutagenesis identified two residues within the λ chain, N31 and S91, that are essential to the functional maturation of ZK2B10. The repertoire and lineage features unveiled here will help elucidate the developmental process and protective potential of E DIII-directed antibodies against ZIKV infection.",2019 Oct 24,"['Gao, Fei', 'Lin, Xiaohe', 'He, Linling', 'Wang, Ruoke', 'Wang, Han', 'Shi, Xuanling', 'Zhang, Fuchun', 'Yin, Chibiao', 'Zhang, Linqi', 'Zhu, Jiang', 'Yu, Lei']",Front Immunol,,,True
794f8c40e63dc3f6a3a6893a0acdc4731126db1c,PMC,Development of a Potent and Protective Germline-Like Antibody Lineage Against Zika Virus in a Convalescent Human,http://dx.doi.org/10.3389/fimmu.2019.02424,PMC6821881,31708914,CC BY,"Zika virus (ZIKV) specific neutralizing antibodies hold great promise for antibody-based interventions and vaccine design against ZIKV infection. However, their development in infected patients remains unclear. Here, we applied next-generation sequencing (NGS) to probe the dynamic development of a potent and protective ZIKV E DIII-specific antibody ZK2B10 isolated from a ZIKV convalescent individual. The unbiased repertoire analysis showed dramatic changes in the usage of antibody variable region germline genes. However, lineage tracing of ZK2B10 revealed limited somatic hypermutation and transient expansion during the 12 months following the onset of symptoms. The NGS-derived, germline-like ZK2B10 somatic variants neutralized ZIKV potently and protected mice from lethal challenge of ZIKV without detectable cross-reactivity with Dengue virus (DENV). Site-directed mutagenesis identified two residues within the λ chain, N31 and S91, that are essential to the functional maturation of ZK2B10. The repertoire and lineage features unveiled here will help elucidate the developmental process and protective potential of E DIII-directed antibodies against ZIKV infection.",2019 Oct 24,"['Gao, Fei', 'Lin, Xiaohe', 'He, Linling', 'Wang, Ruoke', 'Wang, Han', 'Shi, Xuanling', 'Zhang, Fuchun', 'Yin, Chibiao', 'Zhang, Linqi', 'Zhu, Jiang', 'Yu, Lei']",Front Immunol,,,False
6d06153cd1a8bff48ea762c95c01acc5a53453f2,PMC,Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain,http://dx.doi.org/10.1186/s12974-019-1569-2,PMC6822372,31672161,CC BY,"BACKGROUND: Neuroinflammation can modulate brain development; however, the influence of an acute peripheral immune challenge on neuroinflammatory responses in the early postnatal brain is not well characterized. To address this gap in knowledge, we evaluated the peripheral and central nervous system (CNS) immune responses to a mixed immune challenge in early postnatal rats of varying strains and sex. METHODS: On postnatal day 10 (P10), male and female Lewis and Brown Norway rats were injected intramuscularly with either a mix of bacterial and viral components in adjuvant, adjuvant-only, or saline. Immune responses were evaluated at 2 and 5 days post-challenge. Cytokine and chemokine levels were evaluated in serum and in multiple brain regions using a Luminex multiplex assay. Multi-factor ANOVAs were used to compare analyte levels across treatment groups within strain, sex, and day of sample collection. Numbers and activation status of astrocytes and microglia were also analyzed in the cortex and hippocampus by quantifying immunoreactivity for GFAP, IBA-1, and CD68 in fixed brain slices. Immunohistochemical data were analyzed using a mixed-model regression analysis. RESULTS: Acute peripheral immune challenge differentially altered cytokine and chemokine levels in the serum versus the brain. Within the brain, the cytokine and chemokine response varied between strains, sexes, and days post-challenge. Main findings included differences in T helper (Th) type cytokine responses in various brain regions, particularly the cortex, with respect to IL-4, IL-10, and IL-17 levels. Additionally, peripheral immune challenge altered GFAP and IBA-1 immunoreactivity in the brain in a strain- and sex-dependent manner. CONCLUSIONS: These findings indicate that genetic background and sex influence the CNS response to an acute peripheral immune challenge during early postnatal development. Additionally, these data reinforce that the developmental time point during which the challenge occurs has a distinct effect on the activation of CNS-resident cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-019-1569-2) contains supplementary material, which is available to authorized users.",2019 Oct 31,"['Bruce, Matthew', 'Streifel, Karin M.', 'Boosalis, Casey A.', 'Heuer, Luke', 'González, Eduardo A.', 'Li, Shuyang', 'Harvey, Danielle J.', 'Lein, Pamela J.', 'Van de Water, Judy']",J Neuroinflammation,,,True
2eb55c914df79a8b8cee977bac85d06eb07507d4,PMC,Risk of transmission via medical employees and importance of routine infection-prevention policy in a nosocomial outbreak of Middle East respiratory syndrome (MERS): a descriptive analysis from a tertiary care hospital in South Korea,http://dx.doi.org/10.1186/s12890-019-0940-5,PMC6822455,31666061,CC BY,"BACKGROUND: In 2015, South Korea experienced an outbreak of Middle East respiratory syndrome (MERS), and our hospital experienced a nosocomial MERS infection. We performed a comprehensive analysis to identify the MERS transmission route and the ability of our routine infection-prevention policy to control this outbreak. METHODS: This is a case–cohort study of retrospectively analysed data from medical charts, closed-circuit television, personal interviews and a national database. We analysed data of people at risk of MERS transmission including 228 in the emergency department (ED) and 218 in general wards (GW). Data of personnel location and movement, personal protection equipment and hand hygiene was recorded. Transmission risk was determined as the extent of exposure to the index patient: 1) high risk: staying within 2 m; 2) intermediate risk: staying in the same room at same time; and 3) low risk: only staying in the same department without contact. RESULTS: The index patient was an old patient admitted to our hospital. 11 transmissions from the index patient were identified; 4 were infected in our hospital. Personnel in the ED exhibited higher rates of compliance with routine infection-prevention methods as observed objectively: 93% wore a surgical mask and 95.6% washed their hands. Only 1.8% of personnel were observed to wear a surgical mask in the GW. ED had a higher percentage of high-risk individuals compared with the GW (14.5% vs. 2.8%), but the attack rate was higher in the GW (16.7%; l/6) than in the ED (3%; 1/33). There were no transmissions in the intermediate- and low-risk groups in the ED. Otherwise 2 patients were infected in the GW among the low-risk group. MERS were transmitted to them indirectly by staff who cared for the index patient. CONCLUSIONS: Our study provide compelling evidence that routine infection-prevention policies can greatly reduce nosocomial transmission of MERS. Conventional isolation is established mainly from contact tracing of patients during a MERS outbreak. But it should be extended to all people treated by any medical employee who has contact with MERS patients. TRIAL REGISTRATION: NCT02605109, date of registration: 11th November 2015.",2019 Oct 30,"['Ki, Hyun Kyun', 'Han, Sang Kuk', 'Son, Jun Seong', 'Park, Sang O']",BMC Pulm Med,,,True
c79cfa0bb8017217a2626f1b4aafdfdab162a8ce,PMC,Quantitative Proteomics Reveal Peroxiredoxin Perturbation Upon Persistent Lymphocytic Choriomeningitis Virus Infection in Human Cells,http://dx.doi.org/10.3389/fmicb.2019.02438,PMC6823195,31708904,CC BY,"Experimental data indicate that during persistent infection, lymphocytic choriomeningitis virus (LCMV) may both directly or indirectly modulate regulatory cellular processes and alter cellular functions that are not critical for survival, but are essential for cell homeostasis. In order to shed more light on these processes, two-dimensional differential in-gel electrophoresis (2D-DIGE) and MALDI-TOF tandem mass spectrometry were used to determine the proteome response of the HeLa cell line to persistent LCMV infection. Quantitative analysis revealed 24 differentially abundant proteins. Functional analysis showed that LCMV-responsive proteins were primarily involved in metabolism, stress, and the defense response. Among identified proteins, we discovered significant changes for peroxiredoxins, a family of antioxidant enzymes. Decreased amount of these antioxidant proteins correlated with elevation of reactive oxygen species (ROS) in infected cells. Increased levels of ROS were accompanied by changes in the pattern of telomere restriction fragments (TRFs) in infected cells and mediated activation of hypoxia-inducible transcription factor-1 (HIF-1) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. Moreover, treatment with antioxidants resulted in reduced levels of viral nucleoprotein, indicating a connection between ROS-dependent signaling and viral replication.",2019 Oct 25,"['Benej, Martin', 'Danchenko, Maksym', 'Oveckova, Ingrid', 'Cervenak, Filip', 'Tomaska, Lubomir', 'Grossmannova, Katarina', 'Polcicova, Katarina', 'Golias, Tereza', 'Tomaskova, Jana']",Front Microbiol,,,True
91dc59536a7c1113cc9bef3fbb8972ea8555b0f6,PMC,GLIPR1L1 is an IZUMO-binding protein required for optimal fertilization in the mouse,http://dx.doi.org/10.1186/s12915-019-0701-1,PMC6824042,31672133,CC BY,"BACKGROUND: The sperm protein IZUMO1 (Izumo sperm-egg fusion 1) and its recently identified binding partner on the oolemma, IZUMO1R, are among the first ligand-receptor pairs shown to be essential for gamete recognition and adhesion. However, the IZUMO1-IZUMO1R interaction does not appear to be directly responsible for promoting the fusion of the gamete membranes, suggesting that this critical phase of the fertilization cascade requires the concerted action of alternative fusogenic machinery. It has therefore been proposed that IZUMO1 may play a secondary role in the organization and/or stabilization of higher-order heteromeric complexes in spermatozoa that are required for membrane fusion. RESULTS: Here, we show that fertilization-competent (acrosome reacted) mouse spermatozoa harbor several high molecular weight protein complexes, a subset of which are readily able to adhere to solubilized oolemmal proteins. At least two of these complexes contain IZUMO1 in partnership with GLI pathogenesis-related 1 like 1 (GLIPR1L1). This interaction is associated with lipid rafts and is dynamically remodeled upon the induction of acrosomal exocytosis in preparation for sperm adhesion to the oolemma. Accordingly, the selective ablation of GLIPR1L1 leads to compromised sperm function characterized by a reduced ability to undergo the acrosome reaction and a failure of IZUMO1 redistribution. CONCLUSIONS: Collectively, this study characterizes multimeric protein complexes on the sperm surface and identifies GLIPRL1L1 as a physiologically relevant regulator of IZUMO1 function and the fertilization process.",2019 Oct 31,"['Gaikwad, Avinash S.', 'Anderson, Amanda L.', 'Merriner, D. Jo', 'O’Connor, Anne E.', 'Houston, Brendan J.', 'Aitken, R. John', 'O’Bryan, Moira K.', 'Nixon, Brett']",BMC Biol,,,True
1275c64d711b3973f7e25ebc72bbc7c99341dd00,PMC,Alphaherpesvirus infection of mice primes PNS neurons to an inflammatory state regulated by TLR2 and type I IFN signaling,http://dx.doi.org/10.1371/journal.ppat.1008087,PMC6824567,31675371,CC BY,"Pseudorabies virus (PRV), an alphaherpesvirus closely related to Varicella-Zoster virus (VZV) and Herpes simplex type 1 (HSV1) infects mucosa epithelia and the peripheral nervous system (PNS) of its host. We previously demonstrated that PRV infection induces a specific and lethal inflammatory response, contributing to severe neuropathy in mice. So far, the mechanisms that initiate this neuroinflammation remain unknown. Using a mouse footpad inoculation model, we found that PRV infection rapidly and simultaneously induces high G-CSF and IL-6 levels in several mouse tissues, including the footpad, PNS and central nervous system (CNS) tissues. Interestingly, this global increase occurred before PRV had replicated in dorsal root ganglia (DRGs) neurons and also was independent of systemic inflammation. These high G-CSF and IL-6 levels were not caused by neutrophil infiltration in PRV infected tissues, as we did not detect any neutrophils. Efficient PRV replication and spread in the footpad was sufficient to activate DRGs to produce cytokines. Finally, by using knockout mice, we demonstrated that TLR2 and IFN type I play crucial roles in modulating the early neuroinflammatory response and clinical outcome of PRV infection in mice. Overall, these results give new insights into the initiation of virus-induced neuroinflammation during herpesvirus infections.",2019 Nov 1,"['Laval, Kathlyn', 'Van Cleemput, Jolien', 'Vernejoul, Jonah B.', 'Enquist, Lynn W.']",PLoS Pathog,,,True
80ae0645a59c66f34ce7fe53fba4a00404b1c740,PMC,A bibliometric analysis of IL-35 research from 2009 to 2018,http://dx.doi.org/10.7717/peerj.7992,PMC6825408,31687283,CC BY,"BACKGROUND: Interleukin-35 (IL-35) is a recently discovered cytokine that plays a role in immune suppression and has therefore been the subject of a great deal of research. A bibliometric analysis of the global research concerning IL-35, however, is rare. OBJECTIVES: The aim of this research was to assess the international scientific output of IL-35 research and explore its hotspots and frontiers from 2009 to 2018 by bibliometric analysis. METHODS: Publications about IL-35 research from 2009 to 2018 were retrieved from the Web of Science Core Collection (WoSCC). Citespace V was used to analyze years, journals, countries, research institutions, areas of exploration, research hotspots, and trends of publication. RESULTS: We retrieved a total of 416 publications and observed a trend of publications increasing over the past decade. Original articles (351) were the most frequently occurring document type. The largest number of publications belonging to one country and one institution, respectively, was China (202) and Tianjin Medical University (17). Trending keywords may indicate frontier topics, including “infectious tolerance,” “autoimmune,” and “central nervous system.” CONCLUSION: This study provides valuable information on the study of IL-35 so that researchers may identify new research fields.",2019 Oct 30,"['Cai, Xulong', 'Zhou, Chenrong', 'Zhou, Li', 'Xu, Qiaolan']",PeerJ,,,True
0116dea9b6d4c58748d1a38b69b4fe6e06868aa4,PMC,Heterogeneity and plasticity of porcine alveolar macrophage and pulmonary interstitial macrophage isolated from healthy pigs in vitro,http://dx.doi.org/10.1242/bio.046342,PMC6826289,31615770,CC BY,"This study investigated the heterogeneity and plasticity of porcine alveolar macrophages (PAM) and pulmonary interstitial macrophages (IM) isolated from healthy pigs, including phenotype, function and gene expression. Dynamic changes of nitric oxide (NO) levels secreted by PAM and IM with stimulation of different doses of lipopolysaccharide (LPS) were investigated by Griess method, and the viability of the PAM and IM cells was investigated by MTT assay. Flow cytometry, fluorescence quantitative PCR and ELISA techniques were used to measure cell phenotype, gene expression and cytokine secretion, respectively. The PAM and IM cells in normal healthy pigs showed heterogeneity with 95.42±1.51% and 31.99±5.84% of CD163+ macrophage, respectively. The NO level in IM was significantly higher versus PAM after LPS treatment. Consistently, the ratio of Arg I/iNOS in IM was much lower than that in PAM, suggesting that the PAM belong to M2 macrophages and the IM belong to M1 macrophages. The PAM and IM cells in normal healthy pigs also showed plasticity. The Arg I/iNOS ratio and TIMP1/MMP12 ratio were significantly decreased in LPS- or LPS+IFNγ-treated PAM and IM, suggesting that cells were polarized towards M1 macrophages under LPS or LPS+IFNγ stimulation. On the contrary, IL-4 and IL-13 stimulation on PAM and IM lead to M2 polarization. A similar result was found in IL-1β gene expression and TNFα secretion. In conclusion, porcine macrophages have shown heterogeneity and plasticity on polarization under the stimulation of LPS, IFNγ, IL-4 and IL-13.",2019 Oct 15,"['Liu, Huan', 'Liu, Jia', 'Huang, Jing', 'Bai, Xianchang', 'Wang, Qinfu']",Biol Open,,,True
088207699688d96fe973df88c1add87ac8339645,PMC,Immunostimulants in respiratory diseases: focus on Pidotimod,http://dx.doi.org/10.1186/s40248-019-0195-2,PMC6827234,31700623,CC BY,"Usefulness of Pidotimod and its role as immunostimulant, has been discussed, we know, for several decades. Nevertheless, there is still much to know. Understanding its mechanisms and its potential usefulness in airway infections and its prevention, asthma both Th2 and non Th2 type, bronchiectasis, as adjuvant in vaccination and in allergen immunotherapy still remains to clearly unveil. The aim of this paper was to provide a useful updated review of the role of the main available immunostimulants, giving particular focus on Pidotimod use and its potentials utility in respiratory diseases. Pidotimod showed its usefulness in reducing need for antibiotics in airway infections, increasing the level of immunoglobulins (IgA, IgM, IgG) and T-lymphocyte subsets (CD3+, CD4+) endowed with immunomodulatory activity that affect both innate and adaptive immune responses. Higher expression of TLR2 and of HLA-DR molecules, induction of dendritic cell maturation and release of pro-inflammatory molecules, stimulation of T lymphocyte proliferation and differentiation toward a Th1 phenotype, as well as an increase of the phagocytosis have been demonstrated to be associated with Pidotimod in in vitro studies. All these activities are potentially useful for several respiratory conditions such as asthma, COPD, and recurrent respiratory tract infections.",2019 Nov 4,"['Puggioni, Francesca', 'Alves-Correia, Magna', 'Mohamed, Manar-Farouk', 'Stomeo, Niccolò', 'Mager, Riccardo', 'Marinoni, Massimiliano', 'Racca, Francesca', 'Paoletti, Giovanni', 'Varricchi, Gilda', 'Giorgis, Veronica', 'Melioli, Giovanni', 'Canonica, Giorgio Walter', 'Heffler, Enrico']",Multidiscip Respir Med,,,True
522970c3ab7dfd56f03358b19739d66ce7219097,PMC,"Using Non-Invasive Monitoring Technologies to Capture Behavioural, Physiological and Health Responses of Dairy Calves to Different Nutritional Regimes during the First Ten Weeks of Life",http://dx.doi.org/10.3390/ani9100760,PMC6827363,31581685,CC BY,"SIMPLE SUMMARY: Recent research has debated the effects of milk and forage feeding regimes in the first weeks of life on the future performance of dairy calves. However, little is known about how feeding regime can affect behavioural and physiological responses, which have the potential to impact on calf health and well-being. Traditional methods of assessing calf health and welfare such as behavioural observations and blood sampling can be time consuming and impractical for producers and invasive for animals involved. Developments in technology have increased the availability of on-farm non-invasive devices which allow automatic and remote collection of behavioural and physiological data linked to animal health and welfare. This study aimed to use devices to measure lying behaviour, heart rate, heart rate variability and infrared temperature of calves offered high or low levels of milk replacer and different types of forage throughout the first ten weeks of life. Calves displayed changes in lying behaviour and heart rate variability as a result of changes in milk replacer feeding frequency. Additionally, infrared temperature changes were detected during periods of vaccination which corresponded with a rise in core body temperature. Results have highlighted that these sensors can provide important and useable data regarding overall calf well-being on commercial farms. ABSTRACT: This study aimed to examine the use of non-invasive monitoring technologies as a means of capturing behavioural, physiological and health responses of calves allocated to different nutritional regimes. Seventy-four Holstein Friesian calves were individually penned and allocated to receive either high (HML) or conventional (CML) milk replacer (MR) levels between 5–70 days of age. Additionally calves were allocated to one of four forage treatments: (i) chopped straw offered between 14–70 days of age (CS14), (ii) chopped straw offered between 56–70 days of age (CS56), (iii) grass silage offered between 56–70 days of age (GS56), and (iv) no forage in the pre-wean period (NF). A representative sample of calves from each treatment were fitted with activity sensors and heart rate monitors throughout the experimental period to examine lying behaviour and heart rate variability, respectively. Thermal images of the eye and rectal area of each calf were taken 5 days/week between 5–77 days of age. Faecal and respiratory scoring of each individual calf was carried out on a daily basis throughout the experimental period. Milk replacer feeding level had limited effects on measures of calf health, although HML calves tended to have an increased likelihood for receiving treatment for scour than CML calves. Daily lying time (min/d) was lower in HML calves following reduction in MR feeding frequency at 43 days of age and weaning at 71 days of age when compared with CML calves. Additionally, HML calves displayed a lower heart rate variability following weaning, this suggestive of increased stress load. There were limited effects of forage treatment, however, CS14 calves displayed a greater daily lying time following MR step-down at 68 days of age, this potentially indicating increased rumination. Results of the present study highlight the benefits of using remote monitoring technologies as a means of detecting behavioural and physiological changes as a result of nutritional management strategy in individually housed dairy calves.",2019 Oct 2,"['Scoley, Gillian', 'Gordon, Alan', 'Morrison, Steven']",Animals (Basel),,,True
4b01f4156e98d50e6d1dc147d1f1319b56fc3a05,PMC,"Using Non-Invasive Monitoring Technologies to Capture Behavioural, Physiological and Health Responses of Dairy Calves to Different Nutritional Regimes during the First Ten Weeks of Life",http://dx.doi.org/10.3390/ani9100760,PMC6827363,31581685,CC BY,"SIMPLE SUMMARY: Recent research has debated the effects of milk and forage feeding regimes in the first weeks of life on the future performance of dairy calves. However, little is known about how feeding regime can affect behavioural and physiological responses, which have the potential to impact on calf health and well-being. Traditional methods of assessing calf health and welfare such as behavioural observations and blood sampling can be time consuming and impractical for producers and invasive for animals involved. Developments in technology have increased the availability of on-farm non-invasive devices which allow automatic and remote collection of behavioural and physiological data linked to animal health and welfare. This study aimed to use devices to measure lying behaviour, heart rate, heart rate variability and infrared temperature of calves offered high or low levels of milk replacer and different types of forage throughout the first ten weeks of life. Calves displayed changes in lying behaviour and heart rate variability as a result of changes in milk replacer feeding frequency. Additionally, infrared temperature changes were detected during periods of vaccination which corresponded with a rise in core body temperature. Results have highlighted that these sensors can provide important and useable data regarding overall calf well-being on commercial farms. ABSTRACT: This study aimed to examine the use of non-invasive monitoring technologies as a means of capturing behavioural, physiological and health responses of calves allocated to different nutritional regimes. Seventy-four Holstein Friesian calves were individually penned and allocated to receive either high (HML) or conventional (CML) milk replacer (MR) levels between 5–70 days of age. Additionally calves were allocated to one of four forage treatments: (i) chopped straw offered between 14–70 days of age (CS14), (ii) chopped straw offered between 56–70 days of age (CS56), (iii) grass silage offered between 56–70 days of age (GS56), and (iv) no forage in the pre-wean period (NF). A representative sample of calves from each treatment were fitted with activity sensors and heart rate monitors throughout the experimental period to examine lying behaviour and heart rate variability, respectively. Thermal images of the eye and rectal area of each calf were taken 5 days/week between 5–77 days of age. Faecal and respiratory scoring of each individual calf was carried out on a daily basis throughout the experimental period. Milk replacer feeding level had limited effects on measures of calf health, although HML calves tended to have an increased likelihood for receiving treatment for scour than CML calves. Daily lying time (min/d) was lower in HML calves following reduction in MR feeding frequency at 43 days of age and weaning at 71 days of age when compared with CML calves. Additionally, HML calves displayed a lower heart rate variability following weaning, this suggestive of increased stress load. There were limited effects of forage treatment, however, CS14 calves displayed a greater daily lying time following MR step-down at 68 days of age, this potentially indicating increased rumination. Results of the present study highlight the benefits of using remote monitoring technologies as a means of detecting behavioural and physiological changes as a result of nutritional management strategy in individually housed dairy calves.",2019 Oct 2,"['Scoley, Gillian', 'Gordon, Alan', 'Morrison, Steven']",Animals (Basel),,,False
315f0a94d6ac0655e0e5defec4f9526641c76037,PMC,Role of rhesus macaque IFITM3(2) in simian immunodeficiency virus infection of macaques,http://dx.doi.org/10.1371/journal.pone.0224082,PMC6827983,31682595,CC BY,"The experimental infection of rhesus macaques (rh) with simian immunodeficiency virus (SIV) is an important model for human immunodeficiency virus (HIV) infection of humans. The interferon-induced transmembrane protein 3 (IFITM3) inhibits HIV and SIV infection at the stage of host cell entry. However, it is still unclear to what extent the antiviral activity of IFITM3 observed in cell culture translates into inhibition of HIV/SIV spread in the infected host. We have shown previously that although rhIFITM3 inhibits SIV entry into cultured cells, polymorphisms in the rhIFITM3 gene are not strongly associated with viral load or disease progression in SIV infected macaques. Here, we examined whether rhIFITM3(2), which is closely related to rhIFITM3 at the sequence level, exerts antiviral activity and whether polymorphisms in the rhIFITM3(2) gene impact the course of SIV infection. We show that expression of rhIFITM3(2) is interferon-inducible and inhibits SIV entry into cells, although with reduced efficiency as compared to rhIFITM3. We further report the identification of 19 polymorphisms in the rhIFITM3(2) gene. However, analysis of a well characterized cohort of SIV infected macaques revealed that none of the polymorphisms had a significant impact upon the course of SIV infection. These results and our previous work suggest that polymorphisms in the rhIFITM3 and rhIFITM3(2) genes do not strongly modulate the course of SIV infection in macaques.",2019 Nov 4,"['Winkler, Michael', 'Gärtner, Sabine', 'Markus, Lara', 'Hoffmann, Markus', 'Nehlmeier, Inga', 'Krawczak, Michael', 'Sauermann, Ulrike', 'Pöhlmann, Stefan']",PLoS One,,,True
43a1c13f98e327bba213c8d8280dafdc50d11f83,PMC,Role of rhesus macaque IFITM3(2) in simian immunodeficiency virus infection of macaques,http://dx.doi.org/10.1371/journal.pone.0224082,PMC6827983,31682595,CC BY,"The experimental infection of rhesus macaques (rh) with simian immunodeficiency virus (SIV) is an important model for human immunodeficiency virus (HIV) infection of humans. The interferon-induced transmembrane protein 3 (IFITM3) inhibits HIV and SIV infection at the stage of host cell entry. However, it is still unclear to what extent the antiviral activity of IFITM3 observed in cell culture translates into inhibition of HIV/SIV spread in the infected host. We have shown previously that although rhIFITM3 inhibits SIV entry into cultured cells, polymorphisms in the rhIFITM3 gene are not strongly associated with viral load or disease progression in SIV infected macaques. Here, we examined whether rhIFITM3(2), which is closely related to rhIFITM3 at the sequence level, exerts antiviral activity and whether polymorphisms in the rhIFITM3(2) gene impact the course of SIV infection. We show that expression of rhIFITM3(2) is interferon-inducible and inhibits SIV entry into cells, although with reduced efficiency as compared to rhIFITM3. We further report the identification of 19 polymorphisms in the rhIFITM3(2) gene. However, analysis of a well characterized cohort of SIV infected macaques revealed that none of the polymorphisms had a significant impact upon the course of SIV infection. These results and our previous work suggest that polymorphisms in the rhIFITM3 and rhIFITM3(2) genes do not strongly modulate the course of SIV infection in macaques.",2019 Nov 4,"['Winkler, Michael', 'Gärtner, Sabine', 'Markus, Lara', 'Hoffmann, Markus', 'Nehlmeier, Inga', 'Krawczak, Michael', 'Sauermann, Ulrike', 'Pöhlmann, Stefan']",PLoS One,,,False
413d8c5b923d8572615bfb6d7199dad41f4ad370,PMC,Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody,http://dx.doi.org/10.3390/ijms20205073,PMC6829326,31614869,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe aggravating respiratory failure in infected patients, frequently resulting in mechanical ventilation. As limited therapeutic antibody is accumulated in lung tissue following systemic administration, inhalation is newly recognized as an alternative, possibly better, route of therapeutic antibody for pulmonary diseases. The nebulization process, however, generates diverse physiological stresses, and thus, the therapeutic antibody must be resistant to these stresses, remain stable, and form minimal aggregates. We first isolated a MERS-CoV neutralizing antibody that is reactive to the receptor-binding domain (RBD) of spike (S) glycoprotein. To increase stability, we introduced mutations into the complementarity-determining regions (CDRs) of the antibody. In the HCDRs (excluding HCDR3) in this clone, two hydrophobic residues were replaced with Glu, two residues were replaced with Asp, and four residues were replaced with positively charged amino acids. In LCDRs, only two Leu residues were replaced with Val. These modifications successfully generated a clone with significantly greater stability and equivalent reactivity and neutralizing activity following nebulization compared to the original clone. In summary, we generated a MERS-CoV neutralizing human antibody that is reactive to recombinant MERS-CoV S RBD protein for delivery via a pulmonary route by introducing stabilizing mutations into five CDRs.",2019 Oct 12,"['Kim, Sang Il', 'Kim, Sujeong', 'Kim, Jinhee', 'Chang, So Young', 'Shim, Jung Min', 'Jin, Jongwha', 'Lim, Chungsu', 'Baek, Songyi', 'Min, Ji-Young', 'Park, Wan Beom', 'Oh, Myoung-don', 'Kim, Seungtaek', 'Chung, Junho']",Int J Mol Sci,,,True
7ca37fbcd96160332aa69e3bcfade9d9f1bc7210,PMC,Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody,http://dx.doi.org/10.3390/ijms20205073,PMC6829326,31614869,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe aggravating respiratory failure in infected patients, frequently resulting in mechanical ventilation. As limited therapeutic antibody is accumulated in lung tissue following systemic administration, inhalation is newly recognized as an alternative, possibly better, route of therapeutic antibody for pulmonary diseases. The nebulization process, however, generates diverse physiological stresses, and thus, the therapeutic antibody must be resistant to these stresses, remain stable, and form minimal aggregates. We first isolated a MERS-CoV neutralizing antibody that is reactive to the receptor-binding domain (RBD) of spike (S) glycoprotein. To increase stability, we introduced mutations into the complementarity-determining regions (CDRs) of the antibody. In the HCDRs (excluding HCDR3) in this clone, two hydrophobic residues were replaced with Glu, two residues were replaced with Asp, and four residues were replaced with positively charged amino acids. In LCDRs, only two Leu residues were replaced with Val. These modifications successfully generated a clone with significantly greater stability and equivalent reactivity and neutralizing activity following nebulization compared to the original clone. In summary, we generated a MERS-CoV neutralizing human antibody that is reactive to recombinant MERS-CoV S RBD protein for delivery via a pulmonary route by introducing stabilizing mutations into five CDRs.",2019 Oct 12,"['Kim, Sang Il', 'Kim, Sujeong', 'Kim, Jinhee', 'Chang, So Young', 'Shim, Jung Min', 'Jin, Jongwha', 'Lim, Chungsu', 'Baek, Songyi', 'Min, Ji-Young', 'Park, Wan Beom', 'Oh, Myoung-don', 'Kim, Seungtaek', 'Chung, Junho']",Int J Mol Sci,,,False
eacaf861a42b91fc9ed93bfffc97a13685747c40,PMC,Glycosylation of Zika Virus is Important in Host–Virus Interaction and Pathogenic Potential,http://dx.doi.org/10.3390/ijms20205206,PMC6829355,31640124,CC BY,"Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults. ZIKV uses glycosylation of its envelope (E) protein to interact with host cell receptors to facilitate entry; these interactions could also be important for designing therapeutics and vaccines. Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells. We found ZIKV E proteins being extensively modified with oligomannose, hybrid and complex N-glycans of a highly heterogeneous nature. Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV. Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.",2019 Oct 21,"['Routhu, Nanda Kishore', 'Lehoux, Sylvain D.', 'Rouse, Emily A.', 'Bidokhti, Mehdi R. M.', 'Giron, Leila B.', 'Anzurez, Alitzel', 'Reid, St Patrick', 'Abdel-Mohsen, Mohamed', 'Cummings, Richard D.', 'Byrareddy, Siddappa N.']",Int J Mol Sci,,,True
e4f2e55e5c44e9cd0817cb53be28534a09089673,PMC,Glycosylation of Zika Virus is Important in Host–Virus Interaction and Pathogenic Potential,http://dx.doi.org/10.3390/ijms20205206,PMC6829355,31640124,CC BY,"Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults. ZIKV uses glycosylation of its envelope (E) protein to interact with host cell receptors to facilitate entry; these interactions could also be important for designing therapeutics and vaccines. Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells. We found ZIKV E proteins being extensively modified with oligomannose, hybrid and complex N-glycans of a highly heterogeneous nature. Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV. Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.",2019 Oct 21,"['Routhu, Nanda Kishore', 'Lehoux, Sylvain D.', 'Rouse, Emily A.', 'Bidokhti, Mehdi R. M.', 'Giron, Leila B.', 'Anzurez, Alitzel', 'Reid, St Patrick', 'Abdel-Mohsen, Mohamed', 'Cummings, Richard D.', 'Byrareddy, Siddappa N.']",Int J Mol Sci,,,False
02480623218229a12cdbc4800defc262f7cc175c,PMC,Breast Cancer Resistance Protein (BCRP/ABCG2) Inhibits Extra Villous Trophoblast Migration: The Impact of Bacterial and Viral Infection,http://dx.doi.org/10.3390/cells8101150,PMC6829363,31561453,CC BY,"Extravillous trophoblasts (EVT) migration into the decidua is critical for establishing placental perfusion and when dysregulated, may lead to pre-eclampsia (PE) and intrauterine growth restriction (IUGR). The breast cancer resistance protein (BCRP; encoded by ABCG2) regulates the fusion of cytotrophoblasts into syncytiotrophoblasts and protects the fetus from maternally derived xenobiotics. Information about BCRP function in EVTs is limited, however placental exposure to bacterial/viral infection leads to BCRP downregulation in syncitiotrophoblasts. We hypothesized that BCRP is involved in the regulation of EVT function and is modulated by infection/inflammation. We report that besides syncitiotrophoblasts and cytotrophoblasts, BCRP is also expressed in EVTs. BCRP inhibits EVT cell migration in HTR8/SVneo (human EVT-like) cells and in human EVT explant cultures, while not affecting cell proliferation. We have also shown that bacterial—lipopolysaccharide (LPS)—and viral antigens—single stranded RNA (ssRNA)—have a profound effect in downregulating ABCG2 and BCRP levels, whilst simultaneously increasing the migration potential of EVT-like cells. Our study reports a novel function of BCRP in early placentation and suggests that exposure of EVTs to maternal infection/inflammation could disrupt their migration potential via the downregulation of BCRP. This could negatively influence placental development/function, contribute to existing obstetric pathologies, and negatively impact pregnancy outcomes and maternal/neonatal health.",2019 Sep 26,"['Lye, Phetcharawan', 'Bloise, Enrrico', 'Nadeem, Lubna', 'Peng, Chun', 'Gibb, William', 'Ortiga-Carvalho, Tania M.', 'Lye, Stephen J.', 'Matthews, Stephen G.']",Cells,,,True
ad58a9c8fca5baf158c0c25aa68a08dc7265d3c8,PMC,Identification and analysis of long non-coding RNAs that are involved in inflammatory process in response to transmissible gastroenteritis virus infection,http://dx.doi.org/10.1186/s12864-019-6156-5,PMC6829948,31684870,CC BY,"BACKGROUND: Transmissible gastroenteritis virus (TGEV) infection can cause acute inflammation. Long noncoding RNAs (lncRNAs) play important roles in a number of biological process including inflammation response. However, whether lncRNAs participate in TGEV-induced inflammation in porcine intestinal epithelial cells (IPECs) is largely unknown. RESULTS: In this study, the next-generation sequencing (NGS) technology was used to analyze the profiles of lncRNAs in Mock and TGEV-infected porcine intestinal epithelial cell-jejunum 2 (IPEC-J2) cell line. A total of 106 lncRNAs were differentially expressed. Many differentially expressed lncRNAs act as elements to competitively attach microRNAs (miRNAs) which target to messenger RNA (mRNAs) to mediate expression of genes that related to toll-like receptors (TLRs), NOD-like receptors (NLRs), tumor necrosis factor (TNF), and RIG-I-like receptors (RLRs) pathways. Functional analysis of the binding proteins and the up/down-stream genes of the differentially expressed lncRNAs revealed that lncRNAs were principally related to inflammatory response. Meanwhile, we found that the differentially expressed lncRNA TCONS_00058367 might lead to a reduction of phosphorylation of transcription factor p65 (p-p65) in TGEV-infected IPEC-J2 cells by negatively regulating its antisense gene promyelocytic leukemia (PML). CONCLUSIONS: The data showed that differentially expressed lncRNAs might be involved in inflammatory response induced by TGEV through acting as miRNA sponges, regulating their up/down-stream genes, or directly binding proteins.",2019 Nov 4,"['Ma, Xuelian', 'Zhao, Xiaomin', 'Wang, Kaili', 'Tang, Xiaoyi', 'Guo, Jianxiong', 'Mi, Mi', 'Qi, Yanping', 'Chang, Lingling', 'Huang, Yong', 'Tong, Dewen']",BMC Genomics,,,True
318aa9dadfa31d9fd971e0a5b074bc37ee44a012,PMC,A binning tool to reconstruct viral haplotypes from assembled contigs,http://dx.doi.org/10.1186/s12859-019-3138-1,PMC6829986,31684876,CC BY,"BACKGROUND: Infections by RNA viruses such as Influenza, HIV still pose a serious threat to human health despite extensive research on viral diseases. One challenge for producing effective prevention and treatment strategies is high intra-species genetic diversity. As different strains may have different biological properties, characterizing the genetic diversity is thus important to vaccine and drug design. Next-generation sequencing technology enables comprehensive characterization of both known and novel strains and has been widely adopted for sequencing viral populations. However, genome-scale reconstruction of haplotypes is still a challenging problem. In particular, haplotype assembly programs often produce contigs rather than full genomes. As a mutation in one gene can mask the phenotypic effects of a mutation at another locus, clustering these contigs into genome-scale haplotypes is still needed. RESULTS: We developed a contig binning tool, VirBin, which clusters contigs into different groups so that each group represents a haplotype. Commonly used features based on sequence composition and contig coverage cannot effectively distinguish viral haplotypes because of their high sequence similarity and heterogeneous sequencing coverage for RNA viruses. VirBin applied prototype-based clustering to cluster regions that are more likely to contain mutations specific to a haplotype. The tool was tested on multiple simulated sequencing data with different haplotype abundance distributions and contig sizes, and also on mock quasispecies sequencing data. The benchmark results with other contig binning tools demonstrated the superior sensitivity and precision of VirBin in contig binning for viral haplotype reconstruction. CONCLUSIONS: In this work, we presented VirBin, a new contig binning tool for distinguishing contigs from different viral haplotypes with high sequence similarity. It competes favorably with other tools on viral contig binning. The source codes are available at: https://github.com/chjiao/VirBin.",2019 Nov 4,"['Chen, Jiao', 'Shang, Jiayu', 'Wang, Jianrong', 'Sun, Yanni']",BMC Bioinformatics,,,False
37d2a557fe2029d7bf6e32dde8fe5728e27ba4a3,PMC,A binning tool to reconstruct viral haplotypes from assembled contigs,http://dx.doi.org/10.1186/s12859-019-3138-1,PMC6829986,31684876,CC BY,"BACKGROUND: Infections by RNA viruses such as Influenza, HIV still pose a serious threat to human health despite extensive research on viral diseases. One challenge for producing effective prevention and treatment strategies is high intra-species genetic diversity. As different strains may have different biological properties, characterizing the genetic diversity is thus important to vaccine and drug design. Next-generation sequencing technology enables comprehensive characterization of both known and novel strains and has been widely adopted for sequencing viral populations. However, genome-scale reconstruction of haplotypes is still a challenging problem. In particular, haplotype assembly programs often produce contigs rather than full genomes. As a mutation in one gene can mask the phenotypic effects of a mutation at another locus, clustering these contigs into genome-scale haplotypes is still needed. RESULTS: We developed a contig binning tool, VirBin, which clusters contigs into different groups so that each group represents a haplotype. Commonly used features based on sequence composition and contig coverage cannot effectively distinguish viral haplotypes because of their high sequence similarity and heterogeneous sequencing coverage for RNA viruses. VirBin applied prototype-based clustering to cluster regions that are more likely to contain mutations specific to a haplotype. The tool was tested on multiple simulated sequencing data with different haplotype abundance distributions and contig sizes, and also on mock quasispecies sequencing data. The benchmark results with other contig binning tools demonstrated the superior sensitivity and precision of VirBin in contig binning for viral haplotype reconstruction. CONCLUSIONS: In this work, we presented VirBin, a new contig binning tool for distinguishing contigs from different viral haplotypes with high sequence similarity. It competes favorably with other tools on viral contig binning. The source codes are available at: https://github.com/chjiao/VirBin.",2019 Nov 4,"['Chen, Jiao', 'Shang, Jiayu', 'Wang, Jianrong', 'Sun, Yanni']",BMC Bioinformatics,,,True
1a07962f8472f03e5159e01b742cf39295db17f5,PMC,Antiviral Activity Against Infectious Bronchitis Virus and Bioactive Components of Hypericum perforatum L.,http://dx.doi.org/10.3389/fphar.2019.01272,PMC6830131,31736754,CC BY,"Hypericum perforatum L., also known as Saint John’s Wort, has been well studied for its chemical composition and pharmacological activity. In this study, the antiviral activities of H. perforatum on infectious bronchitis virus (IBV) were evaluated in vitro and in vivo for the first time. The results of in vitro experiments confirmed that the antiviral component of H. perforatum was ethyl acetate extraction section (HPE), and results showed that treatment with HPE significantly reduced the relative messenger ribonucleic acid (mRNA) expression and virus titer of IBV, and reduced positive green immunofluorescence signal of IBV in chicken embryo kidney (CEK) cells. HPE treatment at doses of 480–120 mg/kg for 5 days, reduced IBV induced injury in the trachea and kidney, moreover, reduced the mRNA expression level of IBV in the trachea and kidney in vivo. The mRNA expression levels of IL-6, tumor necrosis factor alpha (TNF-α), and nuclear factor kappa beta (NF-κB) significantly decreased, but melanoma differentiation-associated protein 5 (MDA5), mitochondrial antiviral signaling gene, interferon alpha (IFN-α), and interferon beta (IFN-β) mRNA levels significantly increased in vitro and in vivo. Our findings demonstrated that HPE had significant anti-IBV effects in vitro and in vivo, respectively. In addition, it is possible owing to up-regulate mRNA expression of type I interferon through the MDA5 signaling pathway and down-regulate mRNA expression of IL-6 and TNF-α via the NF-κB signaling pathway. Moreover, the mainly active compositions of HPE analyzed by high-performance liquid chromatography/electrospray ionization–mass spectroscopy (ESI-MS) are hyperoside, quercitrin, quercetin, pseudohypericin, and hypericin, and a combination of these compounds could mediate the antiviral activities. This might accelerate our understanding of the antiviral effect of H. perforatum and provide new insights into the development of effective therapeutic strategies.",2019 Oct 29,"['Chen, Huijie', 'Muhammad, Ishfaq', 'Zhang, Yue', 'Ren, Yudong', 'Zhang, Ruili', 'Huang, Xiaodan', 'Diao, Lei', 'Liu, Haixin', 'Li, Xunliang', 'Sun, Xiaoqi', 'Abbas, Ghulam', 'Li, Guangxing']",Front Pharmacol,,,True
da00316edfd01f02f8628c4e5740e0b825137634,PMC,"Nipah virus: epidemiology, pathology, immunobiology and advances in diagnosis, vaccine designing and control strategies – a comprehensive review",http://dx.doi.org/10.1080/01652176.2019.1580827,PMC6830995,31006350,CC BY,"Nipah (Nee-pa) viral disease is a zoonotic infection caused by Nipah virus (NiV), a paramyxovirus belonging to the genus Henipavirus of the family Paramyxoviridae. It is a biosafety level-4 pathogen, which is transmitted by specific types of fruit bats, mainly Pteropus spp. which are natural reservoir host. The disease was reported for the first time from the Kampung Sungai Nipah village of Malaysia in 1998. Human-to-human transmission also occurs. Outbreaks have been reported also from other countries in South and Southeast Asia. Phylogenetic analysis affirmed the circulation of two major clades of NiV as based on currently available complete N and G gene sequences. NiV isolates from Malaysia and Cambodia clustered together in NiV-MY clade, whereas isolates from Bangladesh and India clusterered within NiV-BD clade. NiV isolates from Thailand harboured mixed population of sequences. In humans, the virus is responsible for causing rapidly progressing severe illness which might be characterized by severe respiratory illness and/or deadly encephalitis. In pigs below six months of age, respiratory illness along with nervous symptoms may develop. Different types of enzyme-linked immunosorbent assays along with molecular methods based on polymerase chain reaction have been developed for diagnostic purposes. Due to the expensive nature of the antibody drugs, identification of broad-spectrum antivirals is essential along with focusing on small interfering RNAs (siRNAs). High pathogenicity of NiV in humans, and lack of vaccines or therapeutics to counter this disease have attracted attention of researchers worldwide for developing effective NiV vaccine and treatment regimens.",2019 Apr 22,"['Singh, Raj Kumar', 'Dhama, Kuldeep', 'Chakraborty, Sandip', 'Tiwari, Ruchi', 'Natesan, Senthilkumar', 'Khandia, Rekha', 'Munjal, Ashok', 'Vora, Kranti Suresh', 'Latheef, Shyma K.', 'Karthik, Kumaragurubaran', 'Singh Malik, Yashpal', 'Singh, Rajendra', 'Chaicumpa, Wanpen', 'Mourya, Devendra T.']",Vet Q,,,True
bbb4038e28cab7e031d4a60ee4501989aef467aa,PMC,Haploidentical Stem Cell Transplantation in Children With Hematological Malignancies Using αβ(+) T-Cell Receptor and CD19(+) Cell Depleted Grafts: High CD56(dim)/CD56(bright) NK Cell Ratio Early Following Transplantation Is Associated With Lower Relapse Incidence and Better Outcome,http://dx.doi.org/10.3389/fimmu.2019.02504,PMC6831520,31736949,CC BY,"We prospectively analyzed outcomes of haploidentical hematopoietic stem cell transplantation using αβ(+) T-cell receptor/CD19(+) depleted grafts. Sixty-three transplantations were performed in 60 patients. Twenty-eight patients were diagnosed with acute lymphoblastic leukemia (ALL), 27 patients were diagnosed with acute myelogenous leukemia, and in eight other hematological malignancies were diagnosed. Twenty-three were in first complete remission (CR), 20 in second CR, 20 beyond second CR. Four patients developed graft failure. Median time to neutrophil and platelet recovery was 14 (range 9–25) and 10 days (range 7–30), respectively. The probability of non-relapse mortality (NRM) by day +100 after transplantation was 10 ± 4%. With a median follow-up of 28 months, the probability of relapse was 32 ± 6% and disease-free survival was 52 ± 6%. Immune reconstitution was leaded by NK cells. As such, a high CD56(dim/)CD56(bright) NK cell ratio early after transplantation was associated with better disease-free survival (DFS) (≥3.5; 77 ± 8% vs. <3.5; 28 ± 5%; p = 0.001) due to lower relapse incidence (≥3.5; 15 ± 7% vs. <3.5; 37 ± 9%; p = 0.04). T-cell reconstitution was delayed and associated with severe infections after transplant. Viral reactivation/disease and presence of venooclusive disease of liver in the non-caucasian population had a significant impact on NRM. αβ(+) T-cell receptor/CD19(+) cell-depleted haploidentical transplant is associated with good outcomes especially in patients in early phase of disease. A rapid expansion of “mature” natural killer cells early after transplantation resulted on lower probability of relapse, suggesting a graft vs. leukemia effect independent from graft-vs.-host reactions.",2019 Oct 30,"['Diaz, Miguel A.', 'Zubicaray, Josune', 'Molina, Blanca', 'Abad, Lorea', 'Castillo, Ana', 'Sebastian, Elena', 'Galvez, Eva', 'Ruiz, Julia', 'Vicario, Jose Luis', 'Ramirez, Manuel', 'Sevilla, Julian', 'González-Vicent, Marta']",Front Immunol,,,True
bfd00a5ebdeb263fd711f47d41e658d98d10a666,PMC,Haploidentical Stem Cell Transplantation in Children With Hematological Malignancies Using αβ(+) T-Cell Receptor and CD19(+) Cell Depleted Grafts: High CD56(dim)/CD56(bright) NK Cell Ratio Early Following Transplantation Is Associated With Lower Relapse Incidence and Better Outcome,http://dx.doi.org/10.3389/fimmu.2019.02504,PMC6831520,31736949,CC BY,"We prospectively analyzed outcomes of haploidentical hematopoietic stem cell transplantation using αβ(+) T-cell receptor/CD19(+) depleted grafts. Sixty-three transplantations were performed in 60 patients. Twenty-eight patients were diagnosed with acute lymphoblastic leukemia (ALL), 27 patients were diagnosed with acute myelogenous leukemia, and in eight other hematological malignancies were diagnosed. Twenty-three were in first complete remission (CR), 20 in second CR, 20 beyond second CR. Four patients developed graft failure. Median time to neutrophil and platelet recovery was 14 (range 9–25) and 10 days (range 7–30), respectively. The probability of non-relapse mortality (NRM) by day +100 after transplantation was 10 ± 4%. With a median follow-up of 28 months, the probability of relapse was 32 ± 6% and disease-free survival was 52 ± 6%. Immune reconstitution was leaded by NK cells. As such, a high CD56(dim/)CD56(bright) NK cell ratio early after transplantation was associated with better disease-free survival (DFS) (≥3.5; 77 ± 8% vs. <3.5; 28 ± 5%; p = 0.001) due to lower relapse incidence (≥3.5; 15 ± 7% vs. <3.5; 37 ± 9%; p = 0.04). T-cell reconstitution was delayed and associated with severe infections after transplant. Viral reactivation/disease and presence of venooclusive disease of liver in the non-caucasian population had a significant impact on NRM. αβ(+) T-cell receptor/CD19(+) cell-depleted haploidentical transplant is associated with good outcomes especially in patients in early phase of disease. A rapid expansion of “mature” natural killer cells early after transplantation resulted on lower probability of relapse, suggesting a graft vs. leukemia effect independent from graft-vs.-host reactions.",2019 Oct 30,"['Diaz, Miguel A.', 'Zubicaray, Josune', 'Molina, Blanca', 'Abad, Lorea', 'Castillo, Ana', 'Sebastian, Elena', 'Galvez, Eva', 'Ruiz, Julia', 'Vicario, Jose Luis', 'Ramirez, Manuel', 'Sevilla, Julian', 'González-Vicent, Marta']",Front Immunol,,,False
04d02a37dcbb17916d2a5c03288cb9b59000ebba,PMC,"Seroprevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) in public health workers responding to a MERS outbreak in Seoul, Republic of Korea, in 2015",http://dx.doi.org/10.5365/wpsar.2018.9.3.002,PMC6831962,31720054,CC BY,,2019 Jun 6,"['Ryu, Boyeong', 'Cho, Sung-Il', 'Oh, Myoung-don', 'Lee, Jong-Koo', 'Lee, Jaein', 'Hwang, Young-Ok', 'Yang, Jeong-Sun', 'Kim, Sung Soon', 'Bang, Ji Hwan']",Western Pac Surveill Response J,,,True
ad71472308fc72f2b3fe0044ac4bc2f08c4481b6,PMC,Mucosal Immune Response to Feline Enteric Coronavirus Infection,http://dx.doi.org/10.3390/v11100906,PMC6832150,31569783,CC BY,"Feline infectious peritonitis is a devastating, fatal disease of domestic cats caused by a pathogenic mutant virus derived from the ubiquitous feline enteric coronavirus (FECV). Infection by FECV is generally subclinical, and little is known about the mucosal immune response that controls and eliminates the virus. We investigated the mucosal immune response against FECV in an endemically infected breeding colony over a seven-month period. Thirty-three cats were grouped according to FECV seropositivity and fecal virus shedding into naïve/immunologically quiescent, convalescent and actively infected groups. Blood, fecal samples and colon biopsies were collected to assess the mucosal and systemic immunologic and virologic profile. Results showed that cats with active FECV infections have strong systemic IgG and mucosal IgA responses that wane after virus clearance. Significant FECV-specific mucosal T cell IFNγ responses were not detected in any of the three groups. A shift toward an inflammatory state in the mucosa was suggested by increased IL17:FoxP3 expression. However, no histologic abnormalities were observed, and no shifts in lymphocyte subpopulation phenotype or proliferation were noted. Together, the results suggest that control of FECV is mediated by humoral mucosal and systemic responses and that perturbations in the primary reservoir organ (colon) are minimal.",2019 Sep 27,"['Pearson, Morgan', 'LaVoy, Alora', 'Evans, Samantha', 'Vilander, Allison', 'Webb, Craig', 'Graham, Barbara', 'Musselman, Esther', 'LeCureux, Jonathan', 'VandeWoude, Sue', 'Dean, Gregg A.']",Viruses,,,True
ca304a18a0dfe1a3d8db68789a94edbe6359d8b9,PMC,Mucosal Immune Response to Feline Enteric Coronavirus Infection,http://dx.doi.org/10.3390/v11100906,PMC6832150,31569783,CC BY,"Feline infectious peritonitis is a devastating, fatal disease of domestic cats caused by a pathogenic mutant virus derived from the ubiquitous feline enteric coronavirus (FECV). Infection by FECV is generally subclinical, and little is known about the mucosal immune response that controls and eliminates the virus. We investigated the mucosal immune response against FECV in an endemically infected breeding colony over a seven-month period. Thirty-three cats were grouped according to FECV seropositivity and fecal virus shedding into naïve/immunologically quiescent, convalescent and actively infected groups. Blood, fecal samples and colon biopsies were collected to assess the mucosal and systemic immunologic and virologic profile. Results showed that cats with active FECV infections have strong systemic IgG and mucosal IgA responses that wane after virus clearance. Significant FECV-specific mucosal T cell IFNγ responses were not detected in any of the three groups. A shift toward an inflammatory state in the mucosa was suggested by increased IL17:FoxP3 expression. However, no histologic abnormalities were observed, and no shifts in lymphocyte subpopulation phenotype or proliferation were noted. Together, the results suggest that control of FECV is mediated by humoral mucosal and systemic responses and that perturbations in the primary reservoir organ (colon) are minimal.",2019 Sep 27,"['Pearson, Morgan', 'LaVoy, Alora', 'Evans, Samantha', 'Vilander, Allison', 'Webb, Craig', 'Graham, Barbara', 'Musselman, Esther', 'LeCureux, Jonathan', 'VandeWoude, Sue', 'Dean, Gregg A.']",Viruses,,,False
c549c2bfbb9c30559757547bb42f2999cf286723,PMC,Hepatitis E Virus Entry,http://dx.doi.org/10.3390/v11100883,PMC6832200,31547135,CC BY,"Hepatitis E virus (HEV) infection is a major cause of acute hepatitis worldwide. It is transmitted enterically but replicates in the liver. Recent studies indicate that HEV exists in two forms: naked, nonenveloped virions that are shed into feces to mediate inter-host transmission, and membrane-cloaked, quasienveloped virions that circulate in the bloodstream to mediate virus spread within a host. Both virion types are infectious, but differ in the way they infect cells. Elucidating the entry mechanism for both virion types is essential to understand HEV biology and pathogenesis, and is relevant to the development of treatments and preventions for HEV. This review summarizes the current understanding of the cell entry mechanism for these two HEV virion types.",2019 Sep 20,"['Yin, Xin', 'Feng, Zongdi']",Viruses,,,True
356f0fd788357570d8316ea566c88002554745b0,PMC,Characterizing the PRRSV nsp2 Deubiquitinase Reveals Dispensability of Cis-Activity for Replication and a Link of nsp2 to Inflammation Induction,http://dx.doi.org/10.3390/v11100896,PMC6832237,31561412,CC BY,"The papain-like cysteine protease 2 (PLP2) within the N-terminus of the porcine reproductive and respiratory syndrome virus (PRRSV) nsp2 replicase protein specifies a deubiquitinating enzyme (DUB), but its biochemical properties and the role in infection have remained poorly defined. By using in vitro assays, we found that the purified PLP2 could efficiently cleave K63 and K48 linked polyubiquitin chains Ub3-7 in vitro although displaying a differential activity in converting the respective ubiquitin dimers to monomer. The subsequent mutagenesis analyses revealed that the requirement for PLP2 DUB activity surprisingly resembled that for cis-cleavage activity, as several mutations (e.g., D91R, D85R, etc.) that largely ablated the DUB function also blocked the cis- but not trans-proteolytic cleavage of nsp2/3 polyprotein. Moreover, the analyses identified key mutations that could differentiate DUB from PLP2 cis- and trans-cleavage activities. Further reverse genetics analyses revealed the following findings: (i) mutations that largely blocked the DUB activity were all lethal to the virus, (ii) a point mutation T88G that selectively blocked the cis-cleavage activity of PLP2 did not affect viral viability in cell culture, and (iii) an E90Q mutation that did not affect either of the PLP2 activities led to rescue of WT-like virus but displayed significantly reduced ability to induce TNF-α production. Our findings support the possibility that the PLP2 DUB activity, but not cis-cleavage activity, is essential for PRRSV replication. The data also establish a strong link of nsp2 to pro-inflammatory cytokine induction during infection that operates in a manner independent of PLP2 DUB activity.",2019 Sep 26,"['Zhou, Shaochuan', 'Ge, Xinna', 'Kong, Can', 'Liu, Teng', 'Liu, Aijing', 'Gao, Peng', 'Song, Jiangwei', 'Zhou, Lei', 'Guo, Xin', 'Han, Jun', 'Yang, Hanchun']",Viruses,,,True
678d8b16a3e1f7765affe97bf1cc5180fe53abb9,PMC,Characterizing the PRRSV nsp2 Deubiquitinase Reveals Dispensability of Cis-Activity for Replication and a Link of nsp2 to Inflammation Induction,http://dx.doi.org/10.3390/v11100896,PMC6832237,31561412,CC BY,"The papain-like cysteine protease 2 (PLP2) within the N-terminus of the porcine reproductive and respiratory syndrome virus (PRRSV) nsp2 replicase protein specifies a deubiquitinating enzyme (DUB), but its biochemical properties and the role in infection have remained poorly defined. By using in vitro assays, we found that the purified PLP2 could efficiently cleave K63 and K48 linked polyubiquitin chains Ub3-7 in vitro although displaying a differential activity in converting the respective ubiquitin dimers to monomer. The subsequent mutagenesis analyses revealed that the requirement for PLP2 DUB activity surprisingly resembled that for cis-cleavage activity, as several mutations (e.g., D91R, D85R, etc.) that largely ablated the DUB function also blocked the cis- but not trans-proteolytic cleavage of nsp2/3 polyprotein. Moreover, the analyses identified key mutations that could differentiate DUB from PLP2 cis- and trans-cleavage activities. Further reverse genetics analyses revealed the following findings: (i) mutations that largely blocked the DUB activity were all lethal to the virus, (ii) a point mutation T88G that selectively blocked the cis-cleavage activity of PLP2 did not affect viral viability in cell culture, and (iii) an E90Q mutation that did not affect either of the PLP2 activities led to rescue of WT-like virus but displayed significantly reduced ability to induce TNF-α production. Our findings support the possibility that the PLP2 DUB activity, but not cis-cleavage activity, is essential for PRRSV replication. The data also establish a strong link of nsp2 to pro-inflammatory cytokine induction during infection that operates in a manner independent of PLP2 DUB activity.",2019 Sep 26,"['Zhou, Shaochuan', 'Ge, Xinna', 'Kong, Can', 'Liu, Teng', 'Liu, Aijing', 'Gao, Peng', 'Song, Jiangwei', 'Zhou, Lei', 'Guo, Xin', 'Han, Jun', 'Yang, Hanchun']",Viruses,,,False
30793ddad13205696658bbb0a2083c1cd400aab7,PMC,Polyphenol-Rich Extracts from Toona sinensis Bark and Fruit Ameliorate Free Fatty Acid-Induced Lipogenesis through AMPK and LC3 Pathways,http://dx.doi.org/10.3390/jcm8101664,PMC6832244,31614650,CC BY,"Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease found worldwide. The present study aimed to evaluate the mechanisms of inhibiting lipid accumulation in free fatty acid (FFA)-treated HepG2 cells caused by bark and fruit extracts of Toona sinensis (TSB and TSF). FFA induced lipid and triglyceride (TG) accumulation, which was attenuated by TSB and TSF. TSB and/or TSF promoted phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-coA carboxylase and peroxisome proliferator-activated receptor alpha upregulation. Furthermore, TSB and TSF suppressed FFA-induced liver X receptor, sterol regulatory element-binding transcription protein 1, fatty acid synthase, and stearoyl-CoA desaturase 1 protein expression. Moreover, TSB and/or TSF induced phosphorylation of Unc-51 like autophagy-activating kinase and microtubule-associated protein 1A/1B-light chain 3 expressions. Therefore, TSB and TSF relieve lipid accumulation by attenuating lipogenic protein expression, activating the AMPK pathway, and upregulating the autophagic flux to enhance lipid metabolism. Moreover, TSB and TSF reduced TG contents, implying the therapeutic use of TSB and TSF in NAFLD.",2019 Oct 11,"['Chen, Yung-Chia', 'Chen, Hsin-Ju', 'Huang, Bu-Miin', 'Chen, Yu-Chi', 'Chang, Chi-Fen']",J Clin Med,,,True
e2c3f343a974cf7b8d164aee5c680ff65ad8aa71,PMC,Polyphenol-Rich Extracts from Toona sinensis Bark and Fruit Ameliorate Free Fatty Acid-Induced Lipogenesis through AMPK and LC3 Pathways,http://dx.doi.org/10.3390/jcm8101664,PMC6832244,31614650,CC BY,"Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease found worldwide. The present study aimed to evaluate the mechanisms of inhibiting lipid accumulation in free fatty acid (FFA)-treated HepG2 cells caused by bark and fruit extracts of Toona sinensis (TSB and TSF). FFA induced lipid and triglyceride (TG) accumulation, which was attenuated by TSB and TSF. TSB and/or TSF promoted phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-coA carboxylase and peroxisome proliferator-activated receptor alpha upregulation. Furthermore, TSB and TSF suppressed FFA-induced liver X receptor, sterol regulatory element-binding transcription protein 1, fatty acid synthase, and stearoyl-CoA desaturase 1 protein expression. Moreover, TSB and/or TSF induced phosphorylation of Unc-51 like autophagy-activating kinase and microtubule-associated protein 1A/1B-light chain 3 expressions. Therefore, TSB and TSF relieve lipid accumulation by attenuating lipogenic protein expression, activating the AMPK pathway, and upregulating the autophagic flux to enhance lipid metabolism. Moreover, TSB and TSF reduced TG contents, implying the therapeutic use of TSB and TSF in NAFLD.",2019 Oct 11,"['Chen, Yung-Chia', 'Chen, Hsin-Ju', 'Huang, Bu-Miin', 'Chen, Yu-Chi', 'Chang, Chi-Fen']",J Clin Med,,,False
96775ec12c4441b3acb9b9743a9827cc381471cc,PMC,Nosocomial Transmission of Emerging Viruses via Aerosol-Generating Medical Procedures,http://dx.doi.org/10.3390/v11100940,PMC6832307,31614743,CC BY,"Recent nosocomial transmission events of emerging and re-emerging viruses, including Ebola virus, Middle East respiratory syndrome coronavirus, Nipah virus, and Crimean–Congo hemorrhagic fever orthonairovirus, have highlighted the risk of nosocomial transmission of emerging viruses in health-care settings. In particular, concerns and precautions have increased regarding the use of aerosol-generating medical procedures when treating patients with such viral infections. In spite of increasing associations between aerosol-generating medical procedures and the nosocomial transmission of viruses, we still have a poor understanding of the risks of specific procedures and viruses. In order to identify which aerosol-generating medical procedures and emerging viruses pose a high risk to health-care workers, we explore the mechanisms of aerosol-generating medical procedures, as well as the transmission pathways and characteristics of highly pathogenic viruses associated with nosocomial transmission. We then propose how research, both in clinical and experimental settings, could advance current infection control guidelines.",2019 Oct 12,"['Judson, Seth D.', 'Munster, Vincent J.']",Viruses,,,True
ba44a0c7d9af83e5fe417c92353af491ce4dc035,PMC,The S2 Subunit of QX-type Infectious Bronchitis Coronavirus Spike Protein Is an Essential Determinant of Neurotropism,http://dx.doi.org/10.3390/v11100972,PMC6832359,31652591,CC BY,"Some coronaviruses (CoVs) have an extra furin cleavage site (RRKR/S, furin-S2′ site) upstream of the fusion peptide in the spike protein, which plays roles in virion adsorption and fusion. Mutation of the S2′ site of QX genotype (QX-type) infectious bronchitis virus (IBV) spike protein (S) in a recombinant virus background results in higher pathogenicity, pronounced neural symptoms and neurotropism when compared with conditions in wild-type IBV (WT-IBV) infected chickens. In this study, we present evidence suggesting that recombinant IBV with a mutant S2′ site (furin-S2′ site) leads to higher mortality. Infection with mutant IBV induces severe encephalitis and breaks the blood–brain barrier. The results of a neutralization test and immunoprotection experiment show that an original serum and vaccine can still provide effective protection in vivo and in vitro. This is the first demonstration of IBV-induced neural symptoms in chickens with encephalitis and the furin-S2′ site as a determinant of neurotropism.",2019 Oct 22,"['Cheng, Jinlong', 'Zhao, Ye', 'Xu, Gang', 'Zhang, Keran', 'Jia, Wenfeng', 'Sun, Yali', 'Zhao, Jing', 'Xue, Jia', 'Hu, Yanxin', 'Zhang, Guozhong']",Viruses,,,True
dcd7ba50d2dd32e9237d69e920ce1c4fa91f4df9,PMC,Epidemiology of Deltacoronaviruses (δ-CoV) and Gammacoronaviruses (γ-CoV) in Wild Birds in the United States,http://dx.doi.org/10.3390/v11100897,PMC6832366,31561462,CC BY,"Porcine deltacoronavirus (δ-CoV) is the object of extensive research in several countries including the United States. In contrast, the epidemiology of δ-CoVs in wild birds in the US is largely unknown. Our aim was to comparatively assess the prevalence of δ- and γ-CoVs in wild migratory terrestrial and aquatic birds in Arkansas, Illinois, Indiana, Maryland, Mississippi, Missouri, Ohio, Tennessee and Wisconsin. A total of 1236 cloacal/fecal swabs collected during the period 2015–2018 were tested for γ- and δ-CoVs using genus-specific reverse transcription-PCR assays. A total of 61 (4.99%) samples were γ-CoV positive, with up to 29 positive samples per state. In contrast, only 14 samples were positive for δ-CoV (1.14%) with only 1–4 originating from the same state. Thus, unlike previous reports from Asia, γ-CoVs are more prevalent than δ-CoVs in the US, suggesting that δ-CoVs may spread in birds with lower efficiency. This may indicate δ-CoV emerging status and incomplete adaptation to new host species limiting its spread. Phylogenetic analysis of the partial N gene revealed that the newly identified δ-CoV strains were most closely related to the HKU20 (wigeon) strain. Further studies are necessary to investigate the role of aquatic bird δ-CoVs in the epidemiology of δ-CoVs in swine and terrestrial birds.",2019 Sep 26,"['Paim, Francine C.', 'Bowman, Andrew S.', 'Miller, Lauren', 'Feehan, Brandi J.', 'Marthaler, Douglas', 'Saif, Linda J.', 'Vlasova, Anastasia N.']",Viruses,,,True
cb2653d6bccc8ea8da3bb3abef1840d3ba2b9701,PMC,Viral Innate Immune Evasion and the Pathogenesis of Emerging RNA Virus Infections,http://dx.doi.org/10.3390/v11100961,PMC6832425,31635238,CC BY,"Positive-sense single-stranded RNA (+ssRNA) viruses comprise many (re-)emerging human pathogens that pose a public health problem. Our innate immune system and, in particular, the interferon response form the important first line of defence against these viruses. Given their genetic flexibility, these viruses have therefore developed multiple strategies to evade the innate immune response in order to optimize their replication capacity. Already many molecular mechanisms of innate immune evasion by +ssRNA viruses have been identified. However, research addressing the effect of host innate immune evasion on the pathology caused by viral infections is less prevalent in the literature, though very relevant and interesting. Since interferons have been implicated in inflammatory diseases and immunopathology in addition to their protective role in infection, antagonizing the immune response may have an ambiguous effect on the clinical outcome of the viral disease. Therefore, this review discusses what is currently known about the role of interferons and host immune evasion in the pathogenesis of emerging coronaviruses, alphaviruses and flaviviruses.",2019 Oct 18,"['Nelemans, Tessa', 'Kikkert, Marjolein']",Viruses,,,True
b1ebb695b7eb5d98f551f2c3ffd027cc0bab2016,PMC,Viruses in Horses with Neurologic and Respiratory Diseases,http://dx.doi.org/10.3390/v11100942,PMC6832430,31614994,CC BY,"Metagenomics was used to identify viral sequences in the plasma and CSF (cerobrospinal fluid) of 13 horses with unexplained neurological signs and in the plasma and respiratory swabs of 14 horses with unexplained respiratory signs. Equine hepacivirus and two copiparvoviruses (horse parvovirus-CSF and a novel parvovirus) were detected in plasma from neurological cases. Plasma from horses with respiratory signs contained the same two copiparvoviruses plus equine pegivirus D and respiratory swabs contained equine herpes virus 2 and 5. Based on genetic distances the novel copiparvovirus qualified as a member of a new parvovirus species we named Eqcopivirus. These samples plus another 41 plasma samples from healthy horses were tested by real-time PCRs for multiple equine parvoviruses and hepacivirus. Over half the samples tested were positive for one to three viruses with eqcopivirus DNA detected in 20.5%, equine hepacivirus RNA and equine parvovirus-H DNA in 16% each, and horse parvovirus-CSF DNA in 12% of horses. Comparing viral prevalence in plasma none of the now three genetically characterized equine parvoviruses (all in the copiparvovirus genus) was significantly associated with neurological and respiratory signs in this limited sampling.",2019 Oct 14,"['Altan, Eda', 'Li, Yanpeng', 'Sabino-Santos Jr, Gilberto', 'Sawaswong, Vorthon', 'Barnum, Samantha', 'Pusterla, Nicola', 'Deng, Xutao', 'Delwart, Eric']",Viruses,,,True
88511032b2c7ac3a42adf31909cb0c281c079922,PMC,An Exploration of Machine Learning Methods for Robust Boredom Classification Using EEG and GSR Data,http://dx.doi.org/10.3390/s19204561,PMC6832442,31635194,CC BY,"In recent years, affective computing has been actively researched to provide a higher level of emotion-awareness. Numerous studies have been conducted to detect the user’s emotions from physiological data. Among a myriad of target emotions, boredom, in particular, has been suggested to cause not only medical issues but also challenges in various facets of daily life. However, to the best of our knowledge, no previous studies have used electroencephalography (EEG) and galvanic skin response (GSR) together for boredom classification, although these data have potential features for emotion classification. To investigate the combined effect of these features on boredom classification, we collected EEG and GSR data from 28 participants using off-the-shelf sensors. During data acquisition, we used a set of stimuli comprising a video clip designed to elicit boredom and two other video clips of entertaining content. The collected samples were labeled based on the participants’ questionnaire-based testimonies on experienced boredom levels. Using the collected data, we initially trained 30 models with 19 machine learning algorithms and selected the top three candidate classifiers. After tuning the hyperparameters, we validated the final models through 1000 iterations of 10-fold cross validation to increase the robustness of the test results. Our results indicated that a Multilayer Perceptron model performed the best with a mean accuracy of 79.98% (AUC: 0.781). It also revealed the correlation between boredom and the combined features of EEG and GSR. These results can be useful for building accurate affective computing systems and understanding the physiological properties of boredom.",2019 Oct 20,"['Seo, Jungryul', 'Laine, Teemu H.', 'Sohn, Kyung-Ah']",Sensors (Basel),,,True
b73ed47108764542fff45d065e68ec160f10432a,PMC,High Resolution Analysis of Respiratory Syncytial Virus Infection In Vivo,http://dx.doi.org/10.3390/v11100926,PMC6832471,31658630,CC BY,"Human respiratory syncytial virus (HRSV) is a major cause of pediatric infection and also causes disease in the elderly and those with underlying respiratory problems. There is no vaccine for HRSV and anti-viral therapeutics are not broadly applicable. To investigate the effect of HRSV biology in children, nasopharyngeal aspirates were taken from children with different viral loads and a combined high throughput RNAseq and label free quantitative proteomics approach was used to characterize the nucleic acid and proteins in these samples. HRSV proteins were identified in the nasopharyngeal aspirates from infected children, and their abundance correlated with viral load (Ct value), confirming HRSV infection. Analysis of the HRSV genome indicated that the children were infected with sub-group A virus and that minor variants in nucleotide frequency occurred in discrete clusters along the HRSV genome, and within a patient clustered distinctly within the glycoprotein gene. Data from the samples were binned into four groups; no-HRSV infection (control), high viral load (Ct < 20), medium viral load (Ct = 20–25), and low viral load (Ct > 25). Cellular proteins associated with the anti-viral response (e.g., ISG15) were identified in the nasopharyngeal aspirates and their abundance was correlated with viral load. These combined approaches have not been used before to study HRSV biology in vivo and can be readily applied to the study the variation of virus host interactions.",2019 Oct 10,"['Aljabr, Waleed', 'Armstrong, Stuart', 'Rickett, Natasha Y.', 'Pollakis, Georgios', 'Touzelet, Olivier', 'Cloutman-Green, Elaine', 'Matthews, David A.', 'Hiscox, Julian A.']",Viruses,,,True
2718d50101d585d27c5c817dfe2fb1dded056e1a,PMC,Environmental Contamination and Hygienic Measures After Feline Calicivirus Field Strain Infections of Cats in a Research Facility,http://dx.doi.org/10.3390/v11100958,PMC6832521,31627345,CC BY,"Feline calicivirus (FCV) can cause painful oral ulcerations, salivation, gingivitis/stomatitis, fever and depression in infected cats; highly virulent virus variants can lead to fatal epizootic outbreaks. Viral transmission occurs directly or indirectly via fomites. The aim of this study was to investigate the presence and viability of FCV in the environment after sequential oronasal infections of specified pathogen-free cats with two FCV field strains in a research facility. Replicating virus was detected in saliva swabs from all ten cats after the first and in four out of ten cats after the second FCV exposure using virus isolation to identify FCV shedders. In the environment, where cleaning, but no disinfection took place, FCV viral RNA was detectable using RT-qPCR on all tested items and surfaces, including cat hair. However, only very limited evidence was found of replicating virus using virus isolation. Viral RNA remained demonstrable for at least 28 days after shedding had ceased in all cats. Disinfection with 5% sodium bicarbonate (and Incidin(TM) Plus) and barrier measures were effective in that no viral RNA was detectable outside the cat rooms. Our findings are important for any multicat environment to optimize hygienic measures against FCV infection.",2019 Oct 17,"['Spiri, Andrea Monika', 'Meli, Marina Luisa', 'Riond, Barbara', 'Herbert, Imogen', 'Hosie, Margaret J.', 'Hofmann-Lehmann, Regina']",Viruses,,,True
d5dd18b98d06fac67015e3619c8e501ec02ad5a8,PMC,High Diversity and Novel Enteric Viruses in Fecal Viromes of Healthy Wild and Captive Thai Cynomolgus Macaques (Macaca fascicularis),http://dx.doi.org/10.3390/v11100971,PMC6832579,31652508,CC BY,"Cynomolgus macaques are common across South East Asian countries including Thailand. The National Primate Research Center of Thailand, Chulalongkorn University (NPRCT-CU) captures wild-borne cynomolgus macaque for research use. Limited information is available on the enteric viruses and possible zoonotic infections into or from cynomolgus macaques. We characterized and compare the fecal virome of two populations; healthy wild-originated captive cynomolgus macaques (n = 43) reared in NPRCT-CU and healthy wild cynomolgus macaques (n = 35). Over 90% of recognized viral sequence reads amplified from feces were from bacterial viruses. Viruses from seven families of mammalian viruses were also detected (Parvoviridae, Anelloviridae, Picornaviridae, Adenoviridae, Papillomaviridae, Herpesviridae, and Caliciviridae). The genomes of a member of a new picornavirus genus we named Mafapivirus, a primate chapparvovirus, and a circular Rep-encoding single-strand (CRESS) DNA virus were also characterized. Higher abundance of CRESS DNA viruses of unknown tropism and invertebrate-tropic ambidensovirus were detected in wild versus captive macaques likely reflecting dietary differences. Short term rearing in captivity did not have a pronounced effect on the diversity of mammalian viruses of wild cynomolgus macaques. This study is the first report of the fecal virome of cynomolgus macaques, non-human primates frequently used in biomedical research and vaccination studies.",2019 Oct 22,"['Sawaswong, Vorthon', 'Fahsbender, Elizabeth', 'Altan, Eda', 'Kemthong, Taratorn', 'Deng, Xutao', 'Malaivijitnond, Suchinda', 'Payungporn, Sunchai', 'Delwart, Eric']",Viruses,,,True
e0d2f1d5518c3f12943758f45d87e91ddf271c9a,PMC,"Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine",http://dx.doi.org/10.3390/v11100964,PMC6832696,31635418,CC BY,"Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Repurposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FLUAV), niclosamide against HSV-2, brequinar against human immunodeficiency virus 1 (HIV-1), and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vitro and in vivo tests.",2019 Oct 18,"['Andersen, Petter I.', 'Krpina, Klara', 'Ianevski, Aleksandr', 'Shtaida, Nastassia', 'Jo, Eunji', 'Yang, Jaewon', 'Koit, Sandra', 'Tenson, Tanel', 'Hukkanen, Veijo', 'Anthonsen, Marit W.', 'Bjoras, Magnar', 'Evander, Magnus', 'Windisch, Marc P.', 'Zusinaite, Eva', 'Kainov, Denis E.']",Viruses,,,True
46e5064094ed75015cad5a226c704a0dc21b15c1,PMC,Feline Virome—A Review of Novel Enteric Viruses Detected in Cats,http://dx.doi.org/10.3390/v11100908,PMC6832874,31575055,CC BY,"Recent advances in the diagnostic and metagenomic investigations of the feline enteric environment have allowed the identification of several novel viruses that have been associated with gastroenteritis in cats. In the last few years, noroviruses, kobuviruses, and novel parvoviruses have been repetitively detected in diarrheic cats as alone or in mixed infections with other pathogens, raising a number of questions, with particular regards to their pathogenic attitude and clinical impact. In the present article, the current available literature on novel potential feline enteric viruses is reviewed, providing a meaningful update on the etiology, epidemiologic, pathogenetic, clinical, and diagnostic aspects of the infections caused by these pathogens.",2019 Sep 30,"['Di Martino, Barbara', 'Di Profio, Federica', 'Melegari, Irene', 'Marsilio, Fulvio']",Viruses,,,True
7d61637d10c1a4141e24723bb7650f4a73865bc9,PMC,Viruses and Bats,http://dx.doi.org/10.3390/v11100884,PMC6832948,31546572,CC BY,,2019 Sep 21,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.']",Viruses,,,True
eee5a9068ade4c6776f189045115a90a5785e983,PMC,The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland,http://dx.doi.org/10.3390/v11100946,PMC6832964,31615132,CC BY,"The objective of this study was to investigate the presence of equine coronavirus (ECoV) in clinical samples submitted to a diagnostic laboratory in Ireland. A total of 424 clinical samples were examined from equids with enteric disease in 24 Irish counties between 2011 and 2015. A real-time reverse transcription polymerase chain reaction was used to detect ECoV RNA. Nucleocapsid, spike and the region from the p4.7 to p12.7 genes of positive samples were sequenced, and sequence and phylogenetic analyses were conducted. Five samples (1.2%) collected in 2011 and 2013 tested positive for ECoV. Positive samples were collected from adult horses, Thoroughbred foals and a donkey foal. Sequence and/or phylogenetic analysis showed that nucleocapsid, spike and p12.7 genes were highly conserved and were closely related to ECoVs identified in other countries. In contrast, the region from p4.7 and the non-coding region following the p4.7 gene had deletions or insertions. The differences in the p4.7 region between the Irish ECoVs and other ECoVs indicated that the Irish viruses were distinguishable from those circulating in other countries. This is the first report of ECoV detected in both foals and adult horses in Ireland.",2019 Oct 14,"['Nemoto, Manabu', 'Schofield, Warren', 'Cullinane, Ann']",Viruses,,,True
a5116f2570b7d634280893d327aa65b3b67fe8e1,PMC,The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland,http://dx.doi.org/10.3390/v11100946,PMC6832964,31615132,CC BY,"The objective of this study was to investigate the presence of equine coronavirus (ECoV) in clinical samples submitted to a diagnostic laboratory in Ireland. A total of 424 clinical samples were examined from equids with enteric disease in 24 Irish counties between 2011 and 2015. A real-time reverse transcription polymerase chain reaction was used to detect ECoV RNA. Nucleocapsid, spike and the region from the p4.7 to p12.7 genes of positive samples were sequenced, and sequence and phylogenetic analyses were conducted. Five samples (1.2%) collected in 2011 and 2013 tested positive for ECoV. Positive samples were collected from adult horses, Thoroughbred foals and a donkey foal. Sequence and/or phylogenetic analysis showed that nucleocapsid, spike and p12.7 genes were highly conserved and were closely related to ECoVs identified in other countries. In contrast, the region from p4.7 and the non-coding region following the p4.7 gene had deletions or insertions. The differences in the p4.7 region between the Irish ECoVs and other ECoVs indicated that the Irish viruses were distinguishable from those circulating in other countries. This is the first report of ECoV detected in both foals and adult horses in Ireland.",2019 Oct 14,"['Nemoto, Manabu', 'Schofield, Warren', 'Cullinane, Ann']",Viruses,,,False
0586c9a5cbb333e62fb7e18d5239eae3be34d42a,PMC,"Genetic Analysis of Avian Coronavirus Infectious Bronchitis Virus in Yellow Chickens in Southern China over the Past Decade: Revealing the Changes of Genetic Diversity, Dominant Genotypes, and Selection Pressure",http://dx.doi.org/10.3390/v11100898,PMC6833030,31561498,CC BY,"The high mutation rates of infectious bronchitis virus (IBV) pose economic threats to the poultry industry. In order to track the genetic evolutionary of IBV isolates circulating in yellow chickens, we continued to conduct the genetic analyses of the structural genes S1, E, M, and N from 64 IBV isolates in southern China during 2009–2017. The results showed that the dominant genotypes based on the four genes had changed when compared with those during 1985–2008. Based on the S1 gene phylogenetic tree, LX4-type (GI-19) was the most dominant genotype, which was different from that during 1985–2008. The second most dominant genotype was LDT3-A-type, but this genotype disappeared after 2012. New-type 1 (GVI-1) isolates showed increasing tendency and there were four aa (QKEP) located in the hypervariable region (HVR) III and one aa (S) insertion in all the New-type 1 isolates. Both the analyses of amino acid entropy and molecular evolutionary rate revealed that the variations from large to small were S1, E, M, and N. Purifying selection was detected in the S1, E, M, and N gene proteins, which was different from the positive selection during 1985–2008. Six isolates were confirmed to be recombinants, possibly generated from a vaccine virus of the 4/91-type or LDT3-A-type and a circulating virus. The estimated times for the most recent common ancestors based on the S1, E, M, and N genes were the years of 1744, 1893, 1940, and 1945, respectively. Bayesian skyline analysis revealed a sharp decrease in genetic diversity of all the four structural genes after 2010 and since late 2015, the viral population rapidly rose. In conclusion, the IBVs circulating in southern China over the past decade have experienced a remarkable change in genetic diversity, dominant genotypes, and selection pressure, indicating the importance of permanent monitoring of circulating strains and the urgency for developing new vaccines to counteract the emerging LX4-type and New-type IBVs.",2019 Sep 26,"['Fan, Wensheng', 'Tang, Ning', 'Dong, Zhihua', 'Chen, Jiming', 'Zhang, Wen', 'Zhao, Changrun', 'He, Yining', 'Li, Meng', 'Wu, Cuilan', 'Wei, Tianchao', 'Huang, Teng', 'Mo, Meilan', 'Wei, Ping']",Viruses,,,True
f6c3322832e870befdabba94767a6422dfd67d2b,PMC,Nanoparticle-based vaccine development and evaluation against viral infections in pigs,http://dx.doi.org/10.1186/s13567-019-0712-5,PMC6833244,31694705,CC BY,"Virus infections possess persistent health challenges in swine industry leading to severe economic losses worldwide. The economic burden caused by virus infections such as Porcine Reproductive and Respiratory Syndrome Virus, Swine influenza virus, Porcine Epidemic Diarrhea Virus, Porcine Circovirus 2, Foot and Mouth Disease Virus and many others are associated with severe morbidity, mortality, loss of production, trade restrictions and investments in control and prevention practices. Pigs can also have a role in zoonotic transmission of some viral infections to humans. Inactivated and modified-live virus vaccines are available against porcine viral infections with variable efficacy under field conditions. Thus, improvements over existing vaccines are necessary to: (1) Increase the breadth of protection against evolving viral strains and subtypes; (2) Control of emerging and re-emerging viruses; (3) Eradicate viruses localized in different geographic areas; and (4) Differentiate infected from vaccinated animals to improve disease control programs. Nanoparticles (NPs) generated from virus-like particles, biodegradable and biocompatible polymers and liposomes offer many advantages as vaccine delivery platform due to their unique physicochemical properties. NPs help in efficient antigen internalization and processing by antigen presenting cells and activate them to elicit innate and adaptive immunity. Some of the NPs-based vaccines could be delivered through both parenteral and mucosal routes to trigger efficient mucosal and systemic immune responses and could be used to target specific immune cells such as mucosal microfold (M) cells and dendritic cells (DCs). In conclusion, NPs-based vaccines can serve as novel candidate vaccines against several porcine viral infections with the potential to enhance the broader protective efficacy under field conditions. This review highlights the recent developments in NPs-based vaccines against porcine viral pathogens and how the NPs-based vaccine delivery system induces innate and adaptive immune responses resulting in varied level of protective efficacy.",2019 Nov 6,"['Dhakal, Santosh', 'Renukaradhya, Gourapura J.']",Vet Res,,,True
8c44e37bccf0c2a493e1b1754081384fc802d3d9,PMC,The metaRbolomics Toolbox in Bioconductor and beyond,http://dx.doi.org/10.3390/metabo9100200,PMC6835268,31548506,CC BY,"Metabolomics aims to measure and characterise the complex composition of metabolites in a biological system. Metabolomics studies involve sophisticated analytical techniques such as mass spectrometry and nuclear magnetic resonance spectroscopy, and generate large amounts of high-dimensional and complex experimental data. Open source processing and analysis tools are of major interest in light of innovative, open and reproducible science. The scientific community has developed a wide range of open source software, providing freely available advanced processing and analysis approaches. The programming and statistics environment R has emerged as one of the most popular environments to process and analyse Metabolomics datasets. A major benefit of such an environment is the possibility of connecting different tools into more complex workflows. Combining reusable data processing R scripts with the experimental data thus allows for open, reproducible research. This review provides an extensive overview of existing packages in R for different steps in a typical computational metabolomics workflow, including data processing, biostatistics, metabolite annotation and identification, and biochemical network and pathway analysis. Multifunctional workflows, possible user interfaces and integration into workflow management systems are also reviewed. In total, this review summarises more than two hundred metabolomics specific packages primarily available on CRAN, Bioconductor and GitHub.",2019 Sep 23,"['Stanstrup, Jan', 'Broeckling, Corey D.', 'Helmus, Rick', 'Hoffmann, Nils', 'Mathé, Ewy', 'Naake, Thomas', 'Nicolotti, Luca', 'Peters, Kristian', 'Rainer, Johannes', 'Salek, Reza M.', 'Schulze, Tobias', 'Schymanski, Emma L.', 'Stravs, Michael A.', 'Thévenot, Etienne A.', 'Treutler, Hendrik', 'Weber, Ralf J. M.', 'Willighagen, Egon', 'Witting, Michael', 'Neumann, Steffen']",Metabolites,,,True
6fa76790be17b5874ff6402f20c43a89e5caaf43,PMC,"Griffithsin, a Highly Potent Broad-Spectrum Antiviral Lectin from Red Algae: From Discovery to Clinical Application",http://dx.doi.org/10.3390/md17100567,PMC6835697,31590428,CC BY,"Virus entry into a susceptible host cell is the first step in the formation of all viral diseases. Controlling viral infections by disrupting viral entry is advantageous for antibody-mediated neutralization by the host’s immune system and as a preventive and therapeutic antiviral strategy. Recently, several plant-derived carbohydrate-binding proteins (lectins) have emerged as a new class of antiviral biologics by taking advantage of a unique glycosylation pattern only found on the surface of viruses. In particular, a red algae-derived griffithsin (GRFT) protein has demonstrated superior in vitro and in vivo antiviral activity with minimum host toxicity against a variety of clinically relevant, enveloped viruses. This review examines the structural characteristics of GRFT, focusing on its carbohydrate-binding capability. Its in vitro antiviral profiles against human immunodeficiency virus (HIV) are also discussed followed by a description of the results from a combination study using anti-HIV drugs. The results of several studies regarding its novel antiviral mechanism of action are provided in conjunction with an explanation of viral resistance profiles to GRFT. In addition, its in vitro and in vivo host toxicity profiles are summarized with its pharmacokinetic behavior using in vivo efficacy study results. Also, a large-scale production and formulation strategy, as well as a drug delivery strategy, for GRFT as a new class of broad-spectrum microbicides is discussed. Finally, results from two ongoing clinical studies examining GRFT’s effects on viruses are presented.",2019 Oct 6,"Lee, Choongho",Mar Drugs,,,True
40d1dd0f992de32e06c688811ecc8445826cee20,PMC,Recent Advances in Nanovaccines Using Biomimetic Immunomodulatory Materials,http://dx.doi.org/10.3390/pharmaceutics11100534,PMC6835828,31615112,CC BY,"The development of vaccines plays a vital role in the effective control of several fatal diseases. However, effective prophylactic and therapeutic vaccines have yet to be developed for completely curing deadly diseases, such as cancer, malaria, HIV, and serious microbial infections. Thus, suitable vaccine candidates need to be designed to elicit appropriate immune responses. Nanotechnology has been found to play a unique role in the design of vaccines, providing them with enhanced specificity and potency. Nano-scaled materials, such as virus-like particles, liposomes, polymeric nanoparticles (NPs), and protein NPs, have received considerable attention over the past decade as potential carriers for the delivery of vaccine antigens and adjuvants, due to their beneficial advantages, like improved antigen stability, targeted delivery, and long-time release, for which antigens/adjuvants are either encapsulated within, or decorated on, the NP surface. Flexibility in the design of nanomedicine allows for the programming of immune responses, thereby addressing the many challenges encountered in vaccine development. Biomimetic NPs have emerged as innovative natural mimicking biosystems that can be used for a wide range of biomedical applications. In this review, we discuss the recent advances in biomimetic nanovaccines, and their use in anti-bacterial therapy, anti-HIV therapy, anti-malarial therapy, anti-melittin therapy, and anti-tumor immunity.",2019 Oct 14,"['Vijayan, Veena', 'Mohapatra, Adityanarayan', 'Uthaman, Saji', 'Park, In-Kyu']",Pharmaceutics,,,True
2d2670b7397637426c285d293f7e5671d95e0e80,PMC,MHC class I allele diversity in cynomolgus macaques of Vietnamese origin,http://dx.doi.org/10.7717/peerj.7941,PMC6836755,31720104,CC BY,"Cynomolgus macaques (Macaca fascicularis, Mafa) have been used as important experimental animal models for carrying out biomedical researches. The results of biomedical experiments strongly depend on the immunogenetic background of animals, especially on the diversity of major histocompatibility complex (MHC) alleles. However, there is much less information available on the polymorphism of MHC class I genes in cynomolgus macaques, than is currently available for humans. In this study, we have identified 40 Mafa-A and 60 Mafa-B exons 2 and 3 sequences from 30 unrelated cynomolgus macaques of Vietnamese origin. Among these alleles, 28 are novel. As for the remaining 72 known alleles, 15 alleles are shared with other cynomolgus macaque populations and 32 are identical to alleles previously reported in other macaque species. A potential recombination event was observed between Mafa-A1*091:02 and Mafa-A1*057:01. In addition, the Mafa-A1 genes were found to be more diverse than human HLA-A and the functional residues for peptide binding sites (PBS) or TCR binding sites (TBS) in Mafa-A1 have greater variability than that for non-PBS or non-TBS regions. Overall, this study provides important information on the diversity of Mafa-A and Mafa-B alleles from Vietnamese origin, which may help researchers to choose the most appropriate animals for their studies.",2019 Nov 4,"['Huang, Shuting', 'Huang, Xia', 'Li, Shuang', 'Zhu, Mingjun', 'Zhuo, Min']",PeerJ,,,True
e66a8fe189238b1b6ad95b5666df297060bd503c,PMC,MHC class I allele diversity in cynomolgus macaques of Vietnamese origin,http://dx.doi.org/10.7717/peerj.7941,PMC6836755,31720104,CC BY,"Cynomolgus macaques (Macaca fascicularis, Mafa) have been used as important experimental animal models for carrying out biomedical researches. The results of biomedical experiments strongly depend on the immunogenetic background of animals, especially on the diversity of major histocompatibility complex (MHC) alleles. However, there is much less information available on the polymorphism of MHC class I genes in cynomolgus macaques, than is currently available for humans. In this study, we have identified 40 Mafa-A and 60 Mafa-B exons 2 and 3 sequences from 30 unrelated cynomolgus macaques of Vietnamese origin. Among these alleles, 28 are novel. As for the remaining 72 known alleles, 15 alleles are shared with other cynomolgus macaque populations and 32 are identical to alleles previously reported in other macaque species. A potential recombination event was observed between Mafa-A1*091:02 and Mafa-A1*057:01. In addition, the Mafa-A1 genes were found to be more diverse than human HLA-A and the functional residues for peptide binding sites (PBS) or TCR binding sites (TBS) in Mafa-A1 have greater variability than that for non-PBS or non-TBS regions. Overall, this study provides important information on the diversity of Mafa-A and Mafa-B alleles from Vietnamese origin, which may help researchers to choose the most appropriate animals for their studies.",2019 Nov 4,"['Huang, Shuting', 'Huang, Xia', 'Li, Shuang', 'Zhu, Mingjun', 'Zhuo, Min']",PeerJ,,,False
008d980cbcc283a9b707de3d9a02573dde8528ac,PMC,"A pilot study—genetic diversity and population structure of snow leopards of Gilgit-Baltistan, Pakistan, using molecular techniques",http://dx.doi.org/10.7717/peerj.7672,PMC6836756,31720096,CC BY,"BACKGROUND: The Hindu Kush and Karakoram mountain ranges in Pakistan’s northern areas are a natural habitat of the snow leopard (Panthera uncia syn. Uncia uncia) but the ecological studies on this animal are scarce since it is human shy by nature and lives in difficult mountainous tracts. The pilot study is conducted to exploit the genetic diversity and population structure of the snow leopard in this selected natural habitat of the member of the wildcat family in Pakistan. METHOD: About 50 putative scat samples of snow leopard from five localities of Gilgit-Baltistan (Pakistan) along with a control sample of zoo maintained male snow leopard were collected for comparison. Significant quality and quantity of genomic DNA was extracted from scat samples using combined Zhang–phenol–chloroform method and successful amplification of cytochrome c oxidase I gene (190 bp) using mini-barcode primers, seven simple sequence repeats (SSR) markers and Y-linked AMELY gene (200 bp) was done. RESULTS: Cytochrome c oxidase I gene sequencing suggested that 33/50 (66%) scat samples were of snow leopard. AMELY primer suggested that out of 33 amplified samples, 21 (63.63%) scats were from male and 12 (36.36%) from female leopards. Through successful amplification of DNA of 25 out of 33 (75.75%) scat samples using SSR markers, a total of 68 alleles on seven SSR loci were identified, showing low heterozygosity, while high gene flow between population. DISCUSSION: The low gene flow rate among the population results in low genetic diversity causing decreased diversification. This affects the adaptability to climatic changes, thus ultimately resulting in decreased population size of the species.",2019 Nov 4,"['Aruge, Samreen', 'Batool, Hafsa', 'Khan, Fida M.', 'Fakhar-i-Abbas,', 'Janjua, Safia']",PeerJ,,,True
94305928dcc0731a946af0b72fa89c5e79a86546,PMC,Pharmacotherapy of Lower Respiratory Tract Infections in Elderly—Focused on Antibiotics,http://dx.doi.org/10.3389/fphar.2019.01237,PMC6836807,31736751,CC BY,"Lower respiratory tract infections (LRTIs) refer to the inflammation of the trachea, bronchi, bronchioles, and lung tissue. Old people have an increased risk of developing LRTIs compared to young adults. The prevalence of LRTIs in the elderly population is not only related to underlying diseases and aging itself, but also to a variety of clinical issues, such as history of hospitalization, previous antibacterial therapy, mechanical ventilation, antibiotic resistance. These factors mentioned above have led to an increase in the prevalence and mortality of LRTIs in the elderly, and new medical strategies targeting LRTIs in this population are urgently needed. After a systematic review of the current randomized controlled trials and related studies, we recommend novel pharmacotherapies that demonstrate advantages for the management of LRTIs in people over the age of 65. We also briefly reviewed current medications for respiratory communicable diseases in the elderly. Various sources of information were used to ensure all relevant studies were included. We searched Pubmed, MEDLINE (OvidSP), EMBASE (OvidSP), and ClinicalTrials.gov. Strengths and limitations of these drugs were evaluated based on whether they have novelty of mechanism, favorable pharmacokinetic/pharmacodynamic profiles, avoidance of interactions and intolerance, simplicity of dosing, and their ability to cope with challenges which was mainly evaluated by the primary and secondary endpoints. The purpose of this review is to recommend the most promising antibiotics for treatment of LRTIs in the elderly (both in hospital and in the outpatient setting) based on the existing results of clinical studies with the novel antibiotics, and to briefly review current medications for respiratory communicable diseases in the elderly, aiming to a better management of LRTIs in clinical practice.",2019 Oct 31,"['Liu, Yang', 'Zhang, Yan', 'Zhao, Wanyu', 'Liu, Xiaolei', 'Hu, Fengjuan', 'Dong, Birong']",Front Pharmacol,,,True
18592fbe580d07f487157c4f81de8baecd9700e9,PMC,"Infectious vaccine-derived rubella viruses emerge, persist, and evolve in cutaneous granulomas of children with primary immunodeficiencies",http://dx.doi.org/10.1371/journal.ppat.1008080,PMC6837625,31658304,CC0,"Rubella viruses (RV) have been found in an association with granulomas in children with primary immune deficiencies (PID). Here, we report the recovery and characterization of infectious immunodeficiency-related vaccine-derived rubella viruses (iVDRV) from diagnostic skin biopsies of four patients. Sequence evolution within PID hosts was studied by comparison of the complete genomic sequences of the iVDRVs with the genome of the vaccine virus RA27/3. The degree of divergence of each iVDRV correlated with the duration of persistence indicating continuous intrahost evolution. The evolution rates for synonymous and nonsynonymous substitutions were estimated to be 5.7 x 10(−3) subs/site/year and 8.9 x 10(−4) subs/site/year, respectively. Mutational spectra and signatures indicated a major role for APOBEC cytidine deaminases and a secondary role for ADAR adenosine deaminases in generating diversity of iVDRVs. The distributions of mutations across the genes and 3D hotspots for amino acid substitutions in the E1 glycoprotein identified regions that may be under positive selective pressure. Quasispecies diversity was higher in granulomas than in recovered infectious iVDRVs. Growth properties of iVDRVs were assessed in WI-38 fibroblast cultures. None of the iVDRV isolates showed complete reversion to wild type phenotype but the replicative and persistence characteristics of iVDRVs were different from those of the RA27/3 vaccine strain, making predictions of iVDRV transmissibility and teratogenicity difficult. However, detection of iVDRV RNA in nasopharyngeal specimen and poor neutralization of some iVDRV strains by sera from vaccinated persons suggests possible public health risks associated with iVDRV carriers. Detection of IgM antibody to RV in sera of two out of three patients may be a marker of virus persistence, potentially useful for identifying patients with iVDRV before development of lesions. Studies of the evolutionary dynamics of iVDRV during persistence will contribute to development of infection control strategies and antiviral therapies.",2019 Oct 28,"['Perelygina, Ludmila', 'Chen, Min-hsin', 'Suppiah, Suganthi', 'Adebayo, Adebola', 'Abernathy, Emily', 'Dorsey, Morna', 'Bercovitch, Lionel', 'Paris, Kenneth', 'White, Kevin P.', 'Krol, Alfons', 'Dhossche, Julie', 'Torshin, Ivan Y.', 'Saini, Natalie', 'Klimczak, Leszek J.', 'Gordenin, Dmitry A.', 'Zharkikh, Andrey', 'Plotkin, Stanley', 'Sullivan, Kathleen E.', 'Icenogle, Joseph']",PLoS Pathog,,,True
a0682c2b9aabc40d6daca4496ceec2ccd0583aab,PMC,Epitope‐based peptide vaccine design and target site depiction against Middle East Respiratory Syndrome Coronavirus: an immune-informatics study,http://dx.doi.org/10.1186/s12967-019-2116-8,PMC6839065,31703698,CC BY,"BACKGROUND: Middle East Respiratory Syndrome Coronavirus (MERS-COV) is the main cause of lung and kidney infections in developing countries such as Saudi Arabia and South Korea. This infectious single-stranded, positive (+) sense RNA virus enters the host by binding to dipeptidyl-peptide receptors. Since no vaccine is yet available for MERS-COV, rapid case identification, isolation, and infection prevention strategies must be used to combat the spreading of MERS-COV infection. Additionally, there is a desperate need for vaccines and antiviral strategies. METHODS: The present study used immuno-informatics and computational approaches to identify conserved B- and T cell epitopes for the MERS-COV spike (S) protein that may perform a significant role in eliciting the resistance response to MERS-COV infection. RESULTS: Many conserved cytotoxic T-lymphocyte epitopes and discontinuous and linear B-cell epitopes were predicted for the MERS-COV S protein, and their antigenicity and interactions with the human leukocyte antigen (HLA) B7 allele were estimated. Among B-cell epitopes, QLQMGFGITVQYGT displayed the highest antigenicity-score, and was immensely immunogenic. Among T-cell epitopes, MHC class-I peptide YKLQPLTFL and MHC class-II peptide YCILEPRSG were identified as highly antigenic. Furthermore, docking analyses revealed that the predicted peptides engaged in strong bonding with the HLA-B7 allele. CONCLUSION: The present study identified several MERS-COV S protein epitopes that are conserved among various isolates from different countries. The putative antigenic epitopes may prove effective as novel vaccines for eradication and combating of MERS-COV infection.",2019 Nov 8,"['Tahir ul Qamar, Muhammad', 'Saleem, Saman', 'Ashfaq, Usman Ali', 'Bari, Amna', 'Anwar, Farooq', 'Alqahtani, Safar']",J Transl Med,,,True
1fb6893b7abf4b147f4185c6f94a06c79773d3ec,PMC,Temporal Dynamics of Co-circulating Lineages of Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.3389/fmicb.2019.02486,PMC6839445,31736919,CC BY,"Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is the most important endemic pathogen in the U.S. swine industry. Despite control efforts involving improved biosecurity and different vaccination protocols, the virus continues to circulate and evolve. One of the foremost challenges in its control is high levels of genetic and antigenic diversity. Here, we quantify the co-circulation, emergence and sequential turnover of multiple PRRSV lineages in a single swine-producing region in the United States over a span of 9 years (2009–2017). By classifying over 4,000 PRRSV sequences (open-reading frame 5) into phylogenetic lineages and sub-lineages, we document the ongoing diversification and temporal dynamics of the PRRSV population, including the rapid emergence of a novel sub-lineage that appeared to be absent globally pre-2008. In addition, lineage 9 was the most prevalent lineage from 2009 to 2010, but its occurrence fell to 0.5% of all sequences identified per year after 2014, coinciding with the emergence or re-emergence of lineage 1 as the dominant lineage. The sequential dominance of different lineages, as well as three different sub-lineages within lineage 1, is consistent with the immune-mediated selection hypothesis for the sequential turnover in the dominant lineage. As host populations build immunity through natural infection or vaccination toward the most common variant, this dominant (sub-) lineage may be replaced by an emerging variant to which the population is more susceptible. An analysis of patterns of non- synonymous and synonymous mutations revealed evidence of positive selection on immunologically important regions of the genome, further supporting the potential that immune-mediated selection shapes the evolutionary and epidemiological dynamics for this virus. This has important implications for patterns of emergence and re-emergence of genetic variants of PRRSV that have negative impacts on the swine industry. Constant surveillance on PRRSV occurrence is crucial to a better understanding of the epidemiological and evolutionary dynamics of co-circulating viral lineages. Further studies utilizing whole genome sequencing and exploring the extent of cross-immunity between heterologous PRRS viruses could shed further light on PRRSV immunological response and aid in developing strategies that might be able to diminish disease impact.",2019 Nov 1,"['Paploski, Igor Adolfo Dexheimer', 'Corzo, Cesar', 'Rovira, Albert', 'Murtaugh, Michael P.', 'Sanhueza, Juan Manuel', 'Vilalta, Carles', 'Schroeder, Declan C.', 'VanderWaal, Kimberly']",Front Microbiol,,,True
3d1f93d7609417541850546329b3ed113f7aef3c,PMC,"Feline bocavirus-1 associated with outbreaks of hemorrhagic enteritis in household cats: potential first evidence of a pathological role, viral tropism and natural genetic recombination",http://dx.doi.org/10.1038/s41598-019-52902-2,PMC6841677,31705016,CC BY,"Feline bocavirus-1 (FBoV-1) was identified in cats from different households with hemorrhagic enteritis during outbreaks of an unusual clinical presentation of feline panleukopenia virus (FPLV) in Thailand. Use of polymerase chain reaction revealed the presence of the FBoV-1 DNA in several tissues, suggesting hematogenous viremia, with the viral nucleic acid, detected by in situ hybridization (ISH), was localized in intestinal cells and vascular endothelium of intestinal mucosa and serosa, and in necrosis areas primarily in various lymph nodes while FPLV-immunohistochemical analysis revealed viral localization only in cryptal cells, neurons, and limited to leukocytes in the mesenteric lymph node. Full-length coding genome analysis of the Thai FBoV-1 strains isolated from moribund cats revealed three distinct strains with a high between-strain genetic diversity, while genetic recombination in one of the three FBoV-1 strains within the NS1 gene. This is the first report identifying natural genetic recombination of the FBoV-1 and describing the pathology and viral tropism of FBoV-1 infection in cats. Although the role of FBoV-1 associated with systemic infection of these cats remained undetermined, a contributory role of enteric infection of FBoV-1 is possible. Synergistic effects of dual infection with FPLV and FBoV-1 are hypothesized, suggesting more likely severe clinical presentations.",2019 Nov 8,"['Piewbang, Chutchai', 'Kasantikul, Tanit', 'Pringproa, Kidsadagon', 'Techangamsuwan, Somporn']",Sci Rep,,,False
e197a8c2fc80727b35e38ea7aca28d8e6edfb27a,PMC,"Feline bocavirus-1 associated with outbreaks of hemorrhagic enteritis in household cats: potential first evidence of a pathological role, viral tropism and natural genetic recombination",http://dx.doi.org/10.1038/s41598-019-52902-2,PMC6841677,31705016,CC BY,"Feline bocavirus-1 (FBoV-1) was identified in cats from different households with hemorrhagic enteritis during outbreaks of an unusual clinical presentation of feline panleukopenia virus (FPLV) in Thailand. Use of polymerase chain reaction revealed the presence of the FBoV-1 DNA in several tissues, suggesting hematogenous viremia, with the viral nucleic acid, detected by in situ hybridization (ISH), was localized in intestinal cells and vascular endothelium of intestinal mucosa and serosa, and in necrosis areas primarily in various lymph nodes while FPLV-immunohistochemical analysis revealed viral localization only in cryptal cells, neurons, and limited to leukocytes in the mesenteric lymph node. Full-length coding genome analysis of the Thai FBoV-1 strains isolated from moribund cats revealed three distinct strains with a high between-strain genetic diversity, while genetic recombination in one of the three FBoV-1 strains within the NS1 gene. This is the first report identifying natural genetic recombination of the FBoV-1 and describing the pathology and viral tropism of FBoV-1 infection in cats. Although the role of FBoV-1 associated with systemic infection of these cats remained undetermined, a contributory role of enteric infection of FBoV-1 is possible. Synergistic effects of dual infection with FPLV and FBoV-1 are hypothesized, suggesting more likely severe clinical presentations.",2019 Nov 8,"['Piewbang, Chutchai', 'Kasantikul, Tanit', 'Pringproa, Kidsadagon', 'Techangamsuwan, Somporn']",Sci Rep,,,True
7958b1ebf2a14c0fa7482e96e7cc0b43fe156b2e,PMC,Humoral Immunogenicity and Efficacy of a Single Dose of ChAdOx1 MERS Vaccine Candidate in Dromedary Camels,http://dx.doi.org/10.1038/s41598-019-52730-4,PMC6841732,31705137,CC BY,"MERS-CoV seronegative and seropositive camels received a single intramuscular dose of ChAdOx1 MERS, a replication-deficient adenoviral vectored vaccine expressing MERS-CoV spike protein, with further groups receiving control vaccinations. Infectious camels with active naturally acquired MERS-CoV infection, were co-housed with the vaccinated camels at a ratio of 1:2 (infected:vaccinated); nasal discharge and virus titres were monitored for 14 days. Overall, the vaccination reduced virus shedding and nasal discharge (p = 0.0059 and p = 0.0274, respectively). Antibody responses in seropositive camels were enhancedby the vaccine; these camels had a higher average age than seronegative. Older seronegative camels responded more strongly to vaccination than younger animals; and neutralising antibodies were detected in nasal swabs. Further work is required to optimise vaccine regimens for younger seronegative camels.",2019 Nov 8,"['Alharbi, Naif Khalaf', 'Qasim, Ibrahim', 'Almasoud, Abdulrahman', 'Aljami, Haya A.', 'Alenazi, Mohamed W.', 'Alhafufi, Ali', 'Aldibasi, Omar S.', 'Hashem, Anwar M.', 'Kasem, Samy', 'Albrahim, Raed', 'Aldubaib, Musaad', 'Almansour, Ali', 'Temperton, Nigel J.', 'Kupke, Alexandra', 'Becker, Stephan', 'Abu-obaidah, Ali', 'Alkarar, Ali', 'Yoon, In-Kyu', 'Azhar, Esam', 'Lambe, Teresa', 'Bayoumi, Faisal', 'Aldowerij, Ali', 'Ibrahim, Osman H.', 'Gilbert, Sarah C.', 'Balkhy, Hanan H.']",Sci Rep,,,True
f7de41208aece195ba22060365f3e3eb91e43d88,PMC,Humoral Immunogenicity and Efficacy of a Single Dose of ChAdOx1 MERS Vaccine Candidate in Dromedary Camels,http://dx.doi.org/10.1038/s41598-019-52730-4,PMC6841732,31705137,CC BY,"MERS-CoV seronegative and seropositive camels received a single intramuscular dose of ChAdOx1 MERS, a replication-deficient adenoviral vectored vaccine expressing MERS-CoV spike protein, with further groups receiving control vaccinations. Infectious camels with active naturally acquired MERS-CoV infection, were co-housed with the vaccinated camels at a ratio of 1:2 (infected:vaccinated); nasal discharge and virus titres were monitored for 14 days. Overall, the vaccination reduced virus shedding and nasal discharge (p = 0.0059 and p = 0.0274, respectively). Antibody responses in seropositive camels were enhancedby the vaccine; these camels had a higher average age than seronegative. Older seronegative camels responded more strongly to vaccination than younger animals; and neutralising antibodies were detected in nasal swabs. Further work is required to optimise vaccine regimens for younger seronegative camels.",2019 Nov 8,"['Alharbi, Naif Khalaf', 'Qasim, Ibrahim', 'Almasoud, Abdulrahman', 'Aljami, Haya A.', 'Alenazi, Mohamed W.', 'Alhafufi, Ali', 'Aldibasi, Omar S.', 'Hashem, Anwar M.', 'Kasem, Samy', 'Albrahim, Raed', 'Aldubaib, Musaad', 'Almansour, Ali', 'Temperton, Nigel J.', 'Kupke, Alexandra', 'Becker, Stephan', 'Abu-obaidah, Ali', 'Alkarar, Ali', 'Yoon, In-Kyu', 'Azhar, Esam', 'Lambe, Teresa', 'Bayoumi, Faisal', 'Aldowerij, Ali', 'Ibrahim, Osman H.', 'Gilbert, Sarah C.', 'Balkhy, Hanan H.']",Sci Rep,,,True
2edac72833ca59baf4ad11ecf3b0f2a3eda2bd8f,PMC,Evolution of infectious bronchitis virus in the field after homologous vaccination introduction,http://dx.doi.org/10.1186/s13567-019-0713-4,PMC6842459,31706335,CC BY,"Despite the fact that vaccine resistance has been typically considered a rare phenomenon, some episodes of vaccine failure have been reported with increasing frequency in intensively-raised livestock. Infectious bronchitis virus (IBV) is a widespread avian coronavirus, whose control relies mainly on extensive vaccine administration. Unfortunately, the continuous emergence of new vaccine-immunity escaping variants prompts the development of new vaccines. In the present work, a molecular epidemiology study was performed to evaluate the potential role of homologous vaccination in driving IBV evolution. This was undertaken by assessing IBV viral RNA sequences from the ORF encoding the S1 portion of viral surface glycoprotein (S) before and after the introduction of a new live vaccine on broiler farms in northern-Italy. The results of several biostatistics analyses consistently demonstrate the presence of a higher pressure in the post-vaccination period. Natural selection was detected essentially on sites located on the protein surface, within or nearby domains involved in viral attachment or related functions. This evidence strongly supports the action of vaccine-induced immunity in conditioning viral evolution, potentially leading to the emergence of new vaccine-escape variants. The great plasticity of rapidly-evolving RNA-viruses in response to human intervention, which extends beyond the poultry industry, is demonstrated, claiming further attention due to their relevance for animal and especially human health.",2019 Nov 9,"['Franzo, Giovanni', 'Legnardi, Matteo', 'Tucciarone, Claudia Maria', 'Drigo, Michele', 'Martini, Marco', 'Cecchinato, Mattia']",Vet Res,,,False
a4a12b6a24f165bf7a519a2bfa758862ff0c8331,PMC,Evolution of infectious bronchitis virus in the field after homologous vaccination introduction,http://dx.doi.org/10.1186/s13567-019-0713-4,PMC6842459,31706335,CC BY,"Despite the fact that vaccine resistance has been typically considered a rare phenomenon, some episodes of vaccine failure have been reported with increasing frequency in intensively-raised livestock. Infectious bronchitis virus (IBV) is a widespread avian coronavirus, whose control relies mainly on extensive vaccine administration. Unfortunately, the continuous emergence of new vaccine-immunity escaping variants prompts the development of new vaccines. In the present work, a molecular epidemiology study was performed to evaluate the potential role of homologous vaccination in driving IBV evolution. This was undertaken by assessing IBV viral RNA sequences from the ORF encoding the S1 portion of viral surface glycoprotein (S) before and after the introduction of a new live vaccine on broiler farms in northern-Italy. The results of several biostatistics analyses consistently demonstrate the presence of a higher pressure in the post-vaccination period. Natural selection was detected essentially on sites located on the protein surface, within or nearby domains involved in viral attachment or related functions. This evidence strongly supports the action of vaccine-induced immunity in conditioning viral evolution, potentially leading to the emergence of new vaccine-escape variants. The great plasticity of rapidly-evolving RNA-viruses in response to human intervention, which extends beyond the poultry industry, is demonstrated, claiming further attention due to their relevance for animal and especially human health.",2019 Nov 9,"['Franzo, Giovanni', 'Legnardi, Matteo', 'Tucciarone, Claudia Maria', 'Drigo, Michele', 'Martini, Marco', 'Cecchinato, Mattia']",Vet Res,,,False
f318a546b4911926e2f558a8bc14b11f0ab37648,PMC,Evolution of infectious bronchitis virus in the field after homologous vaccination introduction,http://dx.doi.org/10.1186/s13567-019-0713-4,PMC6842459,31706335,CC BY,"Despite the fact that vaccine resistance has been typically considered a rare phenomenon, some episodes of vaccine failure have been reported with increasing frequency in intensively-raised livestock. Infectious bronchitis virus (IBV) is a widespread avian coronavirus, whose control relies mainly on extensive vaccine administration. Unfortunately, the continuous emergence of new vaccine-immunity escaping variants prompts the development of new vaccines. In the present work, a molecular epidemiology study was performed to evaluate the potential role of homologous vaccination in driving IBV evolution. This was undertaken by assessing IBV viral RNA sequences from the ORF encoding the S1 portion of viral surface glycoprotein (S) before and after the introduction of a new live vaccine on broiler farms in northern-Italy. The results of several biostatistics analyses consistently demonstrate the presence of a higher pressure in the post-vaccination period. Natural selection was detected essentially on sites located on the protein surface, within or nearby domains involved in viral attachment or related functions. This evidence strongly supports the action of vaccine-induced immunity in conditioning viral evolution, potentially leading to the emergence of new vaccine-escape variants. The great plasticity of rapidly-evolving RNA-viruses in response to human intervention, which extends beyond the poultry industry, is demonstrated, claiming further attention due to their relevance for animal and especially human health.",2019 Nov 9,"['Franzo, Giovanni', 'Legnardi, Matteo', 'Tucciarone, Claudia Maria', 'Drigo, Michele', 'Martini, Marco', 'Cecchinato, Mattia']",Vet Res,,,False
f8e6c1da1ba9b222863bb9369bfc92a7a908b6e0,PMC,Evolution of infectious bronchitis virus in the field after homologous vaccination introduction,http://dx.doi.org/10.1186/s13567-019-0713-4,PMC6842459,31706335,CC BY,"Despite the fact that vaccine resistance has been typically considered a rare phenomenon, some episodes of vaccine failure have been reported with increasing frequency in intensively-raised livestock. Infectious bronchitis virus (IBV) is a widespread avian coronavirus, whose control relies mainly on extensive vaccine administration. Unfortunately, the continuous emergence of new vaccine-immunity escaping variants prompts the development of new vaccines. In the present work, a molecular epidemiology study was performed to evaluate the potential role of homologous vaccination in driving IBV evolution. This was undertaken by assessing IBV viral RNA sequences from the ORF encoding the S1 portion of viral surface glycoprotein (S) before and after the introduction of a new live vaccine on broiler farms in northern-Italy. The results of several biostatistics analyses consistently demonstrate the presence of a higher pressure in the post-vaccination period. Natural selection was detected essentially on sites located on the protein surface, within or nearby domains involved in viral attachment or related functions. This evidence strongly supports the action of vaccine-induced immunity in conditioning viral evolution, potentially leading to the emergence of new vaccine-escape variants. The great plasticity of rapidly-evolving RNA-viruses in response to human intervention, which extends beyond the poultry industry, is demonstrated, claiming further attention due to their relevance for animal and especially human health.",2019 Nov 9,"['Franzo, Giovanni', 'Legnardi, Matteo', 'Tucciarone, Claudia Maria', 'Drigo, Michele', 'Martini, Marco', 'Cecchinato, Mattia']",Vet Res,,,True
b0d184b70a7b546420ea145dbad4816b90e795eb,PMC,A large-scale genomic investigation of susceptibility to infection and its association with mental disorders in the Danish population,http://dx.doi.org/10.1038/s41398-019-0622-3,PMC6848113,31712607,CC BY,"Infections and mental disorders are two of the major global disease burdens. While correlations between mental disorders and infections have been reported, the possible genetic links between them have not been assessed in large-scale studies. Moreover, the genetic basis of susceptibility to infection is largely unknown, as large-scale genome-wide association studies of susceptibility to infection have been lacking. We utilized a large Danish population-based sample (N = 65,534) linked to nationwide population-based registers to investigate the genetic architecture of susceptibility to infection (heritability estimation, polygenic risk analysis, and a genome-wide association study (GWAS)) and examined its association with mental disorders (comorbidity analysis and genetic correlation). We found strong links between having at least one psychiatric diagnosis and the occurrence of infection (P = 2.16 × 10(−208), OR = 1.72). The SNP heritability of susceptibility to infection ranged from ~2 to ~7% in samples of differing psychiatric diagnosis statuses (suggesting the environment as a major contributor to susceptibility), and polygenic risk scores moderately but significantly explained infection status in an independent sample. We observed a genetic correlation of 0.496 (P = 2.17 × 10(−17)) between a diagnosis of infection and a psychiatric diagnosis. While our GWAS did not identify genome-wide significant associations, we found 90 suggestive (P ≤ 10(−5)) associations for susceptibility to infection. Our findings suggest a genetic component in susceptibility to infection and indicate that the occurrence of infections in individuals with mental illness may be in part genetically driven.",2019 Nov 11,"['Nudel, Ron', 'Wang, Yunpeng', 'Appadurai, Vivek', 'Schork, Andrew J.', 'Buil, Alfonso', 'Agerbo, Esben', 'Bybjerg-Grauholm, Jonas', 'Børglum, Anders D.', 'Daly, Mark J.', 'Mors, Ole', 'Hougaard, David M.', 'Mortensen, Preben B.', 'Werge, Thomas', 'Nordentoft, Merete', 'Thompson, Wesley K.', 'Benros, Michael E.']",Transl Psychiatry,,,False
5a0d8474822c0a07e6a8cd805f0fbf2e17a38680,PMC,A large-scale genomic investigation of susceptibility to infection and its association with mental disorders in the Danish population,http://dx.doi.org/10.1038/s41398-019-0622-3,PMC6848113,31712607,CC BY,"Infections and mental disorders are two of the major global disease burdens. While correlations between mental disorders and infections have been reported, the possible genetic links between them have not been assessed in large-scale studies. Moreover, the genetic basis of susceptibility to infection is largely unknown, as large-scale genome-wide association studies of susceptibility to infection have been lacking. We utilized a large Danish population-based sample (N = 65,534) linked to nationwide population-based registers to investigate the genetic architecture of susceptibility to infection (heritability estimation, polygenic risk analysis, and a genome-wide association study (GWAS)) and examined its association with mental disorders (comorbidity analysis and genetic correlation). We found strong links between having at least one psychiatric diagnosis and the occurrence of infection (P = 2.16 × 10(−208), OR = 1.72). The SNP heritability of susceptibility to infection ranged from ~2 to ~7% in samples of differing psychiatric diagnosis statuses (suggesting the environment as a major contributor to susceptibility), and polygenic risk scores moderately but significantly explained infection status in an independent sample. We observed a genetic correlation of 0.496 (P = 2.17 × 10(−17)) between a diagnosis of infection and a psychiatric diagnosis. While our GWAS did not identify genome-wide significant associations, we found 90 suggestive (P ≤ 10(−5)) associations for susceptibility to infection. Our findings suggest a genetic component in susceptibility to infection and indicate that the occurrence of infections in individuals with mental illness may be in part genetically driven.",2019 Nov 11,"['Nudel, Ron', 'Wang, Yunpeng', 'Appadurai, Vivek', 'Schork, Andrew J.', 'Buil, Alfonso', 'Agerbo, Esben', 'Bybjerg-Grauholm, Jonas', 'Børglum, Anders D.', 'Daly, Mark J.', 'Mors, Ole', 'Hougaard, David M.', 'Mortensen, Preben B.', 'Werge, Thomas', 'Nordentoft, Merete', 'Thompson, Wesley K.', 'Benros, Michael E.']",Transl Psychiatry,,,True
1a383f04a8ddfeba2113f27e82c41d0582feb276,PMC,Equine Rhinitis A Virus Infection in Thoroughbred Racehorses—A Putative Role in Poor Performance?,http://dx.doi.org/10.3390/v11100963,PMC6848918,31635401,CC BY,"The aim of this study was to identify respiratory viruses circulating amongst elite racehorses in a training yard by serological testing of serial samples and to determine their impact on health status and ability to race. A six-month longitudinal study was conducted in 30 Thoroughbred racehorses (21 two-year-olds, five three-year-olds and four four-year-olds) during the Flat racing season. Sera were tested for the presence of antibodies against equine herpesvirus 1 and 4 (EHV-1 and EHV-4) and equine rhinitis viruses A and B (ERAV and ERBV) by complement fixation (CF) and equine arteritis virus (EAV) by ELISA. Antibodies against equine influenza (EI) were measured by haemagglutination inhibition (HI). Only ERAV was circulating in the yard throughout the six-month study period. Seroconversion to ERAV frequently correlated with clinical respiratory disease and was significantly associated with subsequent failure to race (p = 0.0009). Over 55% of the two-year-olds in the study seroconverted to ERAV in May and June. In contrast, only one seroconversion to ERAV was observed in the older horses. They remained free of any signs of respiratory disease and raced successfully throughout the study period. The importance of ERAV as a contributory factor in the interruption of training programmes for young horses may be underestimated.",2019 Oct 18,"['Back, Helena', 'Weld, John', 'Walsh, Cathal', 'Cullinane, Ann']",Viruses,,,True
05620ea699e7dcf77f750bbb52911ea18b005d8f,PMC,Infectious Disease Risk Across the Growing Human-Non Human Primate Interface: A Review of the Evidence,http://dx.doi.org/10.3389/fpubh.2019.00305,PMC6849485,31828053,CC BY,"Most of the human pandemics reported to date can be classified as zoonoses. Among these, there is a long history of infectious diseases that have spread from non-human primates (NHP) to humans. For millennia, indigenous groups that depend on wildlife for their survival were exposed to the risk of NHP pathogens' transmission through animal hunting and wild meat consumption. Usually, exposure is of no consequence or is limited to mild infections. In rare situations, it can be more severe or even become a real public health concern. Since the emergence of acquired immune deficiency syndrome (AIDS), nobody can ignore that an emerging infectious diseases (EID) might spread from NHP into the human population. In large parts of Central Africa and Asia, wildlife remains the primary source of meat and income for millions of people living in rural areas. However, in the past few decades the risk of exposure to an NHP pathogen has taken on a new dimension. Unprecedented breaking down of natural barriers between NHP and humans has increased exposure to health risks for a much larger population, including people living in urban areas. There are several reasons for this: (i) due to road development and massive destruction of ecosystems for agricultural needs, wildlife and humans come into contact more frequently; (ii) due to ecological awareness, many long distance travelers are in search of wildlife discovery, with a particular fascination for African great apes; (iii) due to the attraction for ancient temples and mystical practices, others travelers visit Asian places colonized by NHP. In each case, there is a risk of pathogen transmission through a bite or another route of infection. Beside the individual risk of contracting a pathogen, there is also the possibility of starting a new pandemic. This article reviews the known cases of NHP pathogens' transmission to humans whether they are hunters, travelers, ecotourists, veterinarians, or scientists working on NHP. Although pathogen transmission is supposed to be a rare outcome, Rabies virus, Herpes B virus, Monkeypox virus, Ebola virus, or Yellow fever virus infections are of greater concern and require quick countermeasures from public health professionals.",2019 Nov 5,"['Devaux, Christian A.', 'Mediannikov, Oleg', 'Medkour, Hacene', 'Raoult, Didier']",Front Public Health,,,True
bc343b504f04146857602c5800c99ab7d08162d1,PMC,Immunity‐targeted approaches to the management of chronic and recurrent upper respiratory tract disorders in children,http://dx.doi.org/10.1111/coa.13335,PMC6850198,30920131,CC BY,"BACKGROUND: Upper respiratory tract infections (URTIs), including rhinitis, nasopharyngitis, tonsillitis and otitis media (OM), comprise of 88% of total respiratory infections, especially in children. Therefore effective prevention and treatment of RTIs remain a high priority worldwide. Preclinical and clinical data highlight the rationale for the use and effectiveness of immunity‐targeted approaches, including targeted immunisations and non‐specific immunomodulation in the prevention and management of recurrent upper RTIs. OBJECTIVE OF REVIEW: The idea of this review was to summarise the current evidence and address key questions concerning the use of conservative and immunity‐targeted approaches to recurrent and chronic URTIs, with a focus on the paediatric population. SEARCH STRATEGY/EVALUATION METHOD: Literature searches were conducted in March 2017 and updated in September 2017 using: Academic Search Complete; CENTRAL; Health Source: Nursing/Academic Edition; MEDLINE; clinicaltrials.gov; and Cochrane databases. In total, 84 articles were retrieved and reviewed. Two independent researchers focused on primary and secondary endpoints in systematic reviews, meta‐analyses and randomised, controlled trials, using immunity‐directed strategies as the control group or within a subpopulation of larger studies. Existing guidelines and interventional/observational studies on novel applications were also included. RESULTS: Children are particularly susceptible to RTIs due to the relative immaturity of their immune systems, as well as other potential predisposing factors such as day care attendance and/or toxic environmental factors (eg increased pathogenic microbial exposure and air pollutants). Recurrent URTIs can affect otherwise healthy children, leading to clinical sequelae and complications, including the development of chronic conditions or the need for surgery. Available pre‐clinical and clinical data highlight the rationale for the use and effectiveness of immunity‐targeted approaches, including targeted immunisations (flu and pneumococcal vaccines) and non‐specific immunomodulation (bacterial lysates), in the prevention and management of recurrent croup, tonsillitis, otitis media, recurrent acute rhinosinusitis and chronic rhinosinusitis. CONCLUSIONS: In this review, we summarise the current evidence and provide data demonstrating that some immunity‐targeted strategies, including vaccination and immunomodulation, have proved effective in the treatment and prevention of recurrent and chronic URTIs in children.",2019 Jul 14,"['Feleszko, Wojciech', 'Marengo, Ricardo', 'Vieira, Antonio Sousa', 'Ratajczak, Karol', 'Mayorga Butrón, José Luis']",Clin Otolaryngol,,,True
7bd930b9d1e7df14ab7f3e97fd56dafe3466ad91,PMC,"A Multicompartment SIS Stochastic Model with Zonal Ventilation for the Spread of Nosocomial Infections: Detection, Outbreak Management, and Infection Control",http://dx.doi.org/10.1111/risa.13300,PMC6850612,30925211,CC BY,"In this work, we study the environmental and operational factors that influence airborne transmission of nosocomial infections. We link a deterministic zonal ventilation model for the airborne distribution of infectious material in a hospital ward, with a Markovian multicompartment SIS model for the infection of individuals within this ward, in order to conduct a parametric study on ventilation rates and their effect on the epidemic dynamics. Our stochastic model includes arrival and discharge of patients, as well as the detection of the outbreak by screening events or due to symptoms being shown by infective patients. For each ventilation setting, we measure the infectious potential of a nosocomial outbreak in the hospital ward by means of a summary statistic: the number of infections occurred within the hospital ward until end or declaration of the outbreak. We analytically compute the distribution of this summary statistic, and carry out local and global sensitivity analysis in order to identify the particular characteristics of each ventilation regime with the largest impact on the epidemic spread. Our results show that ward ventilation can have a significant impact on the infection spread, especially under slow detection scenarios or in overoccupied wards, and that decreasing the infection risk for the whole hospital ward might increase the risk in specific areas of the health‐care facility. Moreover, the location of the initial infective individual and the protocol in place for outbreak declaration both form an interplay with ventilation of the ward.",2019 Aug 29,"['López‐García, Martín', 'King, Marco‐Felipe', 'Noakes, Catherine J.']",Risk Anal,,,True
cc7d924053530c0856e59387595309b8b1ea918e,PMC,"A Multicompartment SIS Stochastic Model with Zonal Ventilation for the Spread of Nosocomial Infections: Detection, Outbreak Management, and Infection Control",http://dx.doi.org/10.1111/risa.13300,PMC6850612,30925211,CC BY,"In this work, we study the environmental and operational factors that influence airborne transmission of nosocomial infections. We link a deterministic zonal ventilation model for the airborne distribution of infectious material in a hospital ward, with a Markovian multicompartment SIS model for the infection of individuals within this ward, in order to conduct a parametric study on ventilation rates and their effect on the epidemic dynamics. Our stochastic model includes arrival and discharge of patients, as well as the detection of the outbreak by screening events or due to symptoms being shown by infective patients. For each ventilation setting, we measure the infectious potential of a nosocomial outbreak in the hospital ward by means of a summary statistic: the number of infections occurred within the hospital ward until end or declaration of the outbreak. We analytically compute the distribution of this summary statistic, and carry out local and global sensitivity analysis in order to identify the particular characteristics of each ventilation regime with the largest impact on the epidemic spread. Our results show that ward ventilation can have a significant impact on the infection spread, especially under slow detection scenarios or in overoccupied wards, and that decreasing the infection risk for the whole hospital ward might increase the risk in specific areas of the health‐care facility. Moreover, the location of the initial infective individual and the protocol in place for outbreak declaration both form an interplay with ventilation of the ward.",2019 Aug 29,"['López‐García, Martín', 'King, Marco‐Felipe', 'Noakes, Catherine J.']",Risk Anal,,,True
83e2abcbaa73c0654cdfcd23bf817beeafbc6e37,PMC,Anti-TGEV Miller Strain Infection Effect of Lactobacillus plantarum Supernatant Based on the JAK-STAT1 Signaling Pathway,http://dx.doi.org/10.3389/fmicb.2019.02540,PMC6851170,31781061,CC BY,"Transmissible gastroenteritis (TGE), caused by transmissible gastroenteritis virus (TGEV), is one many gastrointestinal inflections in piglets, characterized by diarrhea, and high mortality. Probiotics are ubiquitous bacteria in animal intestines, which have many functions, such as promoting intestinal peristalsis and maintaining the intestinal balance. We found that the supernatant of the Lp-1 strain of Lactobacillus plantarum, isolated in our laboratory, and named Lp-1s had marked anti-TGEV effect on IPEC-J2 cells. Lp-1s could induce large amounts of interferon-β in IPEC-J2 cells in the early stage (6 h) of infection with TGEV, and increased the level of phosphorylated signal transducer and activator of transcription and its nuclear translocation in the late stage (24–48 h) of infection. This resulted in upregulated expression of interferon-stimulated genes, and increased the transcription and protein expression of antiviral proteins, resulting in an anti-TGEV effect.",2019 Nov 6,"['Wang, Kai', 'Ran, Ling', 'Yan, Tao', 'Niu, Zheng', 'Kan, Zifei', 'Zhang, Yiling', 'Yang, Yang', 'Xie, Luyi', 'Huang, Shilei', 'Yu, Qiuhan', 'Wu, Di', 'Song, Zhenhui']",Front Microbiol,,,True
4d1f54f77265414c23216e284e9bdb257a8e7e26,PMC,Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling,http://dx.doi.org/10.1128/mBio.02414-19,PMC6851283,31719180,CC BY,"Bats are reservoirs for many RNA viruses that are highly pathogenic in humans yet relatively apathogenic in the natural host. It has been suggested that differences in innate immunity are responsible. The antiviral OAS-RNase L pathway is well characterized in humans, but there is little known about its activation and antiviral activity in bats. During infection, OASs, upon sensing double-stranded RNA (dsRNA), produce 2′-5′ oligoadenylates (2-5A), leading to activation of RNase L which degrades viral and host RNA, limiting viral replication. Humans encode three active OASs (OAS1 to -3). Analysis of the Egyptian Rousette bat genome combined with mRNA sequencing from bat RoNi/7 cells revealed three homologous OAS proteins. Interferon alpha treatment or viral infection induced all three OAS mRNAs, but RNase L mRNA is constitutively expressed. Sindbis virus (SINV) or vaccinia virus (VACVΔE3L) infection of wild-type (WT) or OAS1-KO (knockout), OAS2-KO, or MAVS-KO RoNi/7 cells, but not RNase L-KO or OAS3-KO cells, induces robust RNase L activation. SINV replication is 100- to 200-fold higher in the absence of RNase L or OAS3 than in WT cells. However, MAVS-KO had no detectable effect on RNA degradation or replication. Thus, in RoNi/7 bat cells, as in human cells, activation of RNase L during infection and its antiviral activity are dependent primarily on OAS3 while MAVS signaling is not required for the activation of RNase L and restriction of infection. Our findings indicate that OAS proteins serve as pattern recognition receptors (PRRs) to recognize viral dsRNA and that this pathway is a primary response to virus rather than a secondary effect of interferon signaling.",2019 Nov 12,"['Li, Yize', 'Dong, Beihua', 'Wei, Zuzhang', 'Silverman, Robert H.', 'Weiss, Susan R.']",mBio,,,True
c0a3fa45a3d4599c5d0ccd212e4bde23a4253717,PMC,"Performance of surveillance case definitions for respiratory syncytial virus infections through the sentinel influenza surveillance system, Portugal, 2010 to 2018",http://dx.doi.org/10.2807/1560-7917.ES.2019.24.45.1900140,PMC6852315,31718741,CC BY,"BACKGROUND: Well-established influenza surveillance systems (ISS) can be used for respiratory syncytial virus (RSV) surveillance. In Portugal, RSV cases are detected through the ISS using the European Union (EU) influenza-like illness (ILI) case definition. AIM: To investigate clinical predictors for RSV infection and how three case definitions (EU ILI, a modified EU acute respiratory infection, and one respiratory symptom) performed in detecting RSV infections in Portugal. METHODS: This observational retrospective study used epidemiological and laboratory surveillance data (October 2010–May 2018). Associations between clinical characteristics and RSV detection were analysed using logistic regression. Accuracy of case definitions was assessed through sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). A 0.05 significance level was accepted. RESULTS: The study involved 6,523 persons, including 190 (2.9%) RSV cases. Among 183 cases with age information, RSV infection was significantly more frequent among individuals < 5 years (n = 23; 12.6%) and ≥ 65 years (n = 45; 24.6%) compared with other age groups (p < 0.0001). Cough (odds ratio (OR): 2.4; 95% confidence interval (CI): 1.2–6.5) was the best RSV-infection predictor considering all age groups, while shortness of breath was particularly associated with RSV-positivity among ≤ 14 year olds (OR: 6.7; 95% CI: 2.6–17.4 for 0–4 year olds and OR: 6.7; 95% CI: 1.5–28.8 for 5–14 year olds). Systemic symptoms were significantly associated with RSV-negative and influenza-positive cases. None of the case definitions were suitable to detect RSV infections (AUC = 0.51). CONCLUSION: To avoid underestimating the RSV disease burden, RSV surveillance within the Portuguese sentinel ISS would require a more sensitive case definition than ILI and, even a different case definition according to age.",2019 Nov 7,"['Sáez-López, Emma', 'Pechirra, Pedro', 'Costa, Inês', 'Cristóvão, Paula', 'Conde, Patrícia', 'Machado, Ausenda', 'Rodrigues, Ana Paula', 'Guiomar, Raquel']",Euro Surveill,,,True
b04c8cddba2dfb4f953daac916d936924976392d,PMC,Risk factors of 90-day rehospitalization following discharge of pediatric patients hospitalized with mycoplasma Pneumoniae pneumonia,http://dx.doi.org/10.1186/s12879-019-4616-9,PMC6852903,31718584,CC BY,"BACKGROUND: Among pediatric patients hospitalized for Mycoplasma pneumoniae pneumonia (MPP), the risk factors for 90-day readmission after discharge is undefined. METHODS: We conducted a retrospective observational study of patients <14 years of age who were discharged with a diagnosis of MPP between January 2016 and February 2017. We collected clinical, laboratory and radiographic variables at the time of initial admission. We assessed pneumonia-related readmission within 90-day after discharge. Risk factors independently associated with rehospitalization were identified using multiple logistic regression models. RESULTS: Of the 424 MPP hospitalizations, 48 (11.3%) were readmitted within 90 days and were mainly diagnosed with pneumonia. Patients with younger age or coinfection with influenza A were more likely to be readmitted. In addition, compared with children without readmission, the readmission ones showed different clinical and laboratory characteristics at the index hospital admission. Multiple logistic regression analysis identified age (OR 0.815, 95%CI 0.706–0.940) and body temperature (OR 0.659, 95%CI 0.518–0.839) were significantly associated with lower risk of 90-day readmission. Coinfection with influenza was independently associated with a greater likelihood of 90-day readmission (OR 4.746, 95%CI 1.191–18.913). CONCLUSIONS: Readmission after MPP are common and is related to patients’ age, body temperature and influenza A coinfection during initial hospital stay, indicating potential targets could be noticed to reduce the rehospitalization after pediatric MPP.",2019 Nov 12,"['Wang, Le', 'Feng, Zhishan', 'Shuai, Jinfeng', 'Liu, Jianhua', 'Li, Guixia']",BMC Infect Dis,,,True
e48be328050790f8d642f93c224a2bf0d89c19bd,PMC,Development of indirect enzyme-linked immunosorbent assay for detection of porcine epidemic diarrhea virus specific antibodies (IgG) in serum of naturally infected pigs,http://dx.doi.org/10.1186/s12917-019-2123-2,PMC6852973,31718620,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV) infection is a highly contagious infectious disease causing watery diarrhea, vomiting, dehydration and high mortality rate in newborn piglets. PEDV infection can cause high economic losses in pig industry. In Japan, a PEDV outbreak occurred with high mortality from 2013 to 2015. Even though until now, PEDV infection occurs sporadically. For the control and monitoring of PEDV infection, not only symptomatic pigs, but also asymptomatic pigs should be identified. The objective of this study is to develop and optimize novel indirect ELISA as a simple, rapid, sensitive and specific method for the detection of anti-PEDV antibodies and evaluate the efficacy of the assay as a diagnostic method for PED. RESULTS: One hundred sixty-two serum samples, consisting of 81 neutralization test (NT) positive and 81 NT negative sera, were applied to the assay. Indirect ELISA test based on whole virus antigen (NK94P6 strain) derived from Vero cell culture was evaluated by receiver operating characteristic (ROC) analysis with neutralization test (NT) as a reference method, and cut-off value was determined as 0.320 with sensitivity and specificity of 92.6 and 90.1%, respectively. The area under curve (AUC) was 0.949, indicating excellent accuracy of indirect ELISA test. There was significant positive correlation between indirect ELISA and neutralization test (R = 0.815, P < 0.05). Furthermore, the kappa statics showed the excellent agreement between these two tests (kappa value = 0.815). In addition, the sensitivity and specificity of preserved plates with different periods (1 day, 2 weeks, 1, 2, 3, 4, 5 and 6 months) after drying antigen coated plates were 100% and 80–100%, respectively. CONCLUSIONS: The developed indirect ELISA test in our study would be useful as a reliable test for serological survey and disease control of PEDV infection, and our pre-antigen coated ELISA plates can be preserved at 4 °C until at least 6 months.",2019 Nov 12,"['Myint, Ohnmar', 'Yoshida, Ayako', 'Sekiguchi, Satoshi', 'Van Diep, Nguyen', 'Fuke, Naoyuki', 'Izzati, Uda Zahli', 'Hirai, Takuya', 'Yamaguchi, Ryoji']",BMC Vet Res,,,True
d46d1cea1f8f20ffee27303fc83fb2517e4c23fc,PMC,Blocking transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) in llamas by vaccination with a recombinant spike protein,http://dx.doi.org/10.1080/22221751.2019.1685912,PMC6853226,31711379,CC BY,"The ongoing Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks pose a worldwide public health threat. Blocking MERS-CoV zoonotic transmission from dromedary camels, the animal reservoir, could potentially reduce the number of primary human cases. Here we report MERS-CoV transmission from experimentally infected llamas to naïve animals. Directly inoculated llamas shed virus for at least 6 days and could infect all in-contact naïve animals 4–5 days after exposure. With the aim to block virus transmission, we examined the efficacy of a recombinant spike S1-protein vaccine. In contrast to naïve animals, in-contact vaccinated llamas did not shed infectious virus upon exposure to directly inoculated llamas, consistent with the induction of strong virus neutralizing antibody responses. Our data provide further evidence that vaccination of the reservoir host may impede MERS-CoV zoonotic transmission to humans.",2019 Nov 12,"['Rodon, Jordi', 'Okba, Nisreen M. A.', 'Te, Nigeer', 'van Dieren, Brenda', 'Bosch, Berend-Jan', 'Bensaid, Albert', 'Segalés, Joaquim', 'Haagmans, Bart L.', 'Vergara-Alert, Júlia']",Emerg Microbes Infect,,,True
66183bae84bd67df555f2067d092f4da0f979770,PMC,Editorial: Nanoparticle Vaccines Against Infectious Diseases,http://dx.doi.org/10.3389/fimmu.2019.02615,PMC6853890,31787982,CC BY,,2019 Nov 7,"['Reljic, Rajko', 'González-Fernández, África']",Front Immunol,,,False
2b2903114784318062dabce86e330fbbe9309aa8,PMC,The 3.1-Angstrom Cryo-electron Microscopy Structure of the Porcine Epidemic Diarrhea Virus Spike Protein in the Prefusion Conformation,http://dx.doi.org/10.1128/JVI.00923-19,PMC6854500,31534041,CC BY,"Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus that has a significant agricultural and economic impact due to the high mortality rate associated with infection of neonatal piglets. Like other coronaviruses, PEDV makes use of a large, trimeric spike (S) glycoprotein to mediate membrane fusion and gain entry into host cells. Despite the importance of the spike protein in viral entry and host immune responses, high-resolution structural information concerning this large macromolecular machine has been difficult to obtain. Here, we report the cryo-electron microscopy structure of the PEDV S protein in the prefusion conformation at a resolution of 3.1 Å. Our studies revealed that the sialic acid-binding domain at the N terminus of the S1 subunit has an orientation that is substantially different from that observed in the previously determined spike structure from human alphacoronavirus NL63. We also observed dissociated S1 subunit trimers wherein the putative receptor-binding domains exist in a conformation differing from that observed in the intact spike proteins, suggesting that the PEDV receptor-binding domain undergoes conformational rearrangements akin to those that have been described in the related betacoronaviruses. Collectively, these data provide new insights into the biological processes that mediate alphacoronavirus attachment, receptor engagement, and fusion triggering while also identifying a source of conformational heterogeneity that could be manipulated to improve PEDV vaccine antigens. IMPORTANCE Coronavirus spike proteins are large, densely glycosylated macromolecular machines that mediate receptor binding and membrane fusion to facilitate entry into host cells. This report describes the atomic-resolution structure of the spike protein from porcine epidemic diarrhea virus, a pathogenic alphacoronavirus that causes severe agricultural damage. The structure reveals a novel position for the sialic acid-binding attachment domain in the intact spike. We also observed shed fusion-suppressive capping subunits that displayed the putative receptor-binding domain in an accessible conformation. These observations provide a basis for understanding the molecular mechanisms that drive the earliest stages of alphacoronavirus infection and will inform future efforts to rationally design vaccines.",2019 Nov 13,"['Wrapp, Daniel', 'McLellan, Jason S.']",J Virol,,,True
92d48e929d926e032e132ddbe779c20d39bf814d,PMC,The 3.1-Angstrom Cryo-electron Microscopy Structure of the Porcine Epidemic Diarrhea Virus Spike Protein in the Prefusion Conformation,http://dx.doi.org/10.1128/JVI.00923-19,PMC6854500,31534041,CC BY,"Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus that has a significant agricultural and economic impact due to the high mortality rate associated with infection of neonatal piglets. Like other coronaviruses, PEDV makes use of a large, trimeric spike (S) glycoprotein to mediate membrane fusion and gain entry into host cells. Despite the importance of the spike protein in viral entry and host immune responses, high-resolution structural information concerning this large macromolecular machine has been difficult to obtain. Here, we report the cryo-electron microscopy structure of the PEDV S protein in the prefusion conformation at a resolution of 3.1 Å. Our studies revealed that the sialic acid-binding domain at the N terminus of the S1 subunit has an orientation that is substantially different from that observed in the previously determined spike structure from human alphacoronavirus NL63. We also observed dissociated S1 subunit trimers wherein the putative receptor-binding domains exist in a conformation differing from that observed in the intact spike proteins, suggesting that the PEDV receptor-binding domain undergoes conformational rearrangements akin to those that have been described in the related betacoronaviruses. Collectively, these data provide new insights into the biological processes that mediate alphacoronavirus attachment, receptor engagement, and fusion triggering while also identifying a source of conformational heterogeneity that could be manipulated to improve PEDV vaccine antigens. IMPORTANCE Coronavirus spike proteins are large, densely glycosylated macromolecular machines that mediate receptor binding and membrane fusion to facilitate entry into host cells. This report describes the atomic-resolution structure of the spike protein from porcine epidemic diarrhea virus, a pathogenic alphacoronavirus that causes severe agricultural damage. The structure reveals a novel position for the sialic acid-binding attachment domain in the intact spike. We also observed shed fusion-suppressive capping subunits that displayed the putative receptor-binding domain in an accessible conformation. These observations provide a basis for understanding the molecular mechanisms that drive the earliest stages of alphacoronavirus infection and will inform future efforts to rationally design vaccines.",2019 Nov 13,"['Wrapp, Daniel', 'McLellan, Jason S.']",J Virol,,,False
b75e7f3f923023185daed6f29e5beca4eddfc109,PMC,Comprehensive Interactome Analysis Reveals that STT3B Is Required for N-Glycosylation of Lassa Virus Glycoprotein,http://dx.doi.org/10.1128/JVI.01443-19,PMC6854512,31511384,CC BY,"Lassa virus (LASV) is the causative agent of a fatal hemorrhagic fever in humans. The glycoprotein (GP) of LASV mediates viral entry into host cells, and correct processing and modification of GP by host factors is a prerequisite for virus replication. Here, using an affinity purification-coupled mass spectrometry (AP-MS) strategy, 591 host proteins were identified as interactors of LASV GP. Gene ontology analysis was performed to functionally annotate these proteins, and the oligosaccharyltransferase (OST) complex was highly enriched. Functional studies conducted by using CRISPR-Cas9-mediated knockouts showed that STT3A and STT3B, the two catalytically active isoforms of the OST complex, are essential for the propagation of the recombinant arenavirus rLCMV/LASV glycoprotein precursor, mainly via affecting virus infectivity. Knockout of STT3B, but not STT3A, caused hypoglycosylation of LASV GP, indicating a preferential requirement of LASV for the STT3B-OST isoform. Furthermore, double knockout of magnesium transporter 1 (MAGT1) and tumor suppressor candidate 3 (TUSC3), two specific subunits of STT3B-OST, also caused hypoglycosylation of LASV GP and affected virus propagation. Site-directed mutagenesis analysis revealed that the oxidoreductase CXXC active-site motif of MAGT1 or TUSC3 is essential for the glycosylation of LASV GP. NGI-1, a small-molecule OST inhibitor, can effectively reduce virus infectivity without affecting cell viability. The STT3B-dependent N-glycosylation of GP is conserved among other arenaviruses, including both the Old World and New World groups. Our study provided a systematic view of LASV GP-host interactions and revealed the preferential requirement of STT3B for LASV GP N-glycosylation. IMPORTANCE Glycoproteins play vital roles in the arenavirus life cycle by facilitating virus entry and participating in the virus budding process. N-glycosylation of GPs is responsible for their proper functioning; however, little is known about the host factors on which the virus depends for this process. In this study, a comprehensive LASV GP interactome was characterized, and further study revealed that STT3B-dependent N-glycosylation was preferentially required by arenavirus GPs and critical for virus infectivity. The two specific thioredoxin subunits of STT3B-OST MAGT1 and TUSC3 were found to be essential for the N-glycosylation of viral GP. NGI-1, a small-molecule inhibitor of OST, also showed a robust inhibitory effect on arenavirus. Our study provides new insights into LASV GP-host interactions and extends the potential targets for the development of novel therapeutics against Lassa fever in the future.",2019 Nov 13,"['Zhu, Shenglin', 'Wan, Weiwei', 'Zhang, Yanjun', 'Shang, Weijuan', 'Pan, Xiaoyan', 'Zhang, Lei-Ke', 'Xiao, Gengfu']",J Virol,,,True
fd5019fe920bf1eadf48d4d8e9b2f965966b1f75,PMC,"Cicadidae Periostracum, the Cast-Off Skin of Cicada, Protects Dopaminergic Neurons in a Model of Parkinson's Disease",http://dx.doi.org/10.1155/2019/5797512,PMC6854990,31772707,CC BY,"Parkinson's disease (PD) is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta (SNPC) and the striatum. Nuclear receptor-related 1 protein (Nurr1) is a nuclear hormone receptor implicated in limiting mitochondrial dysfunction, apoptosis, and inflammation in the central nervous system and protecting dopaminergic neurons and a promising therapeutic target for PD. Cicadidae Periostracum (CP), the cast-off skin of Cryptotympana pustulata Fabricius, has been used in traditional medicine for its many clinical pharmacological effects, including the treatment of psychological symptoms in PD. However, scientific evidence for the use of CP in neurodegenerative diseases, including PD, is lacking. Here, we investigated the protective effects of CP on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced PD in mice and explored the underlying mechanisms of action, focusing on Nurr1. CP increased the expression levels of Nurr1, tyrosine hydroxylase, DOPA decarboxylase, dopamine transporter, and vesicular monoamine transporter 2 via extracellular signal-regulated kinase phosphorylation in differentiated PC12 cells and the mouse SNPC. In MPTP-induced PD, CP promoted recovery from movement impairments. CP prevented dopamine depletion and protected against dopaminergic neuronal degradation via mitochondria-mediated apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X, cytochrome c, and cleaved caspase-9 and caspase-3 by inhibiting MPTP-induced neuroinflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase 2, and glial/microglial activation. Moreover, CP inhibited lipopolysaccharide-induced neuroinflammatory cytokines and response levels and glial/microglial activation in BV2 microglia and the mouse brain. Our findings suggest that CP might contribute to neuroprotective signaling by regulating neurotrophic factors primarily via Nurr1 signaling, neuroinflammation, and mitochondria-mediated apoptosis.",2019 Oct 24,"['Lim, Hye-Sun', 'Kim, Joong-Sun', 'Moon, Byeong Cheol', 'Choi, Goya', 'Ryu, Seung Mok', 'Lee, Jun', 'Ang, Mary Jasmin', 'Jeon, Mijin', 'Moon, Changjong', 'Park, Gunhyuk']",Oxid Med Cell Longev,,,False
bd6dd93085fa736cac9569090a8cb88324daf18f,PMC,"Cicadidae Periostracum, the Cast-Off Skin of Cicada, Protects Dopaminergic Neurons in a Model of Parkinson's Disease",http://dx.doi.org/10.1155/2019/5797512,PMC6854990,31772707,CC BY,"Parkinson's disease (PD) is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta (SNPC) and the striatum. Nuclear receptor-related 1 protein (Nurr1) is a nuclear hormone receptor implicated in limiting mitochondrial dysfunction, apoptosis, and inflammation in the central nervous system and protecting dopaminergic neurons and a promising therapeutic target for PD. Cicadidae Periostracum (CP), the cast-off skin of Cryptotympana pustulata Fabricius, has been used in traditional medicine for its many clinical pharmacological effects, including the treatment of psychological symptoms in PD. However, scientific evidence for the use of CP in neurodegenerative diseases, including PD, is lacking. Here, we investigated the protective effects of CP on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced PD in mice and explored the underlying mechanisms of action, focusing on Nurr1. CP increased the expression levels of Nurr1, tyrosine hydroxylase, DOPA decarboxylase, dopamine transporter, and vesicular monoamine transporter 2 via extracellular signal-regulated kinase phosphorylation in differentiated PC12 cells and the mouse SNPC. In MPTP-induced PD, CP promoted recovery from movement impairments. CP prevented dopamine depletion and protected against dopaminergic neuronal degradation via mitochondria-mediated apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X, cytochrome c, and cleaved caspase-9 and caspase-3 by inhibiting MPTP-induced neuroinflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase 2, and glial/microglial activation. Moreover, CP inhibited lipopolysaccharide-induced neuroinflammatory cytokines and response levels and glial/microglial activation in BV2 microglia and the mouse brain. Our findings suggest that CP might contribute to neuroprotective signaling by regulating neurotrophic factors primarily via Nurr1 signaling, neuroinflammation, and mitochondria-mediated apoptosis.",2019 Oct 24,"['Lim, Hye-Sun', 'Kim, Joong-Sun', 'Moon, Byeong Cheol', 'Choi, Goya', 'Ryu, Seung Mok', 'Lee, Jun', 'Ang, Mary Jasmin', 'Jeon, Mijin', 'Moon, Changjong', 'Park, Gunhyuk']",Oxid Med Cell Longev,,,True
3a83391556631ba5fbdbef16900ceed1619d69f3,PMC,Effective methods for the inactivation of Francisella tularensis,http://dx.doi.org/10.1371/journal.pone.0225177,PMC6855423,31725770,CC BY,"Francisella tularensis (F. tularensis) is highly pathogenic to humans and must be handled under biosafety level 3 conditions. Samples used for the diagnosis and experimental analysis must be completely inactivated, although methods for the inactivation of F. tularensis are limited. In this study, effective methods for the inactivation of F. tularensis SCHU P9 and five other strains were determined by comparisons of colony-forming units between treated and control samples. The results showed that F. tularensis SCHU P9 was denatured by heat treatment (94°C for 3 min and 56°C for 30 min), filtration with a 0.22 μm filter, and the use of various solutions (i.e. >70% ethanol, methanol, acetone, and 4% paraformaldehyde). F. tularensis SCHU P9 remained viable after treatment with 50% ethanol for 1 min, filtration with a 0.45 μm filter, and treatments with detergents (i.e. 1% lithium dodecyl sulfate buffer, 1% Triton X-100 and 1% Nonidet P-40) at 4°C for 24 h. Additionally, F. tularensis SCHU P9 suspended in fetal bovine serum in plastic tubes was highly resistant to ultraviolet radiation compared to suspensions in water and chemically defined medium. The methods for inactivation of F. tularensis SCHU P9 was applicable to the other five strains of F. tularensis. The data presented in this study could be useful for the establishment of guidelines and standard operating procedures (SOP) to inactivate the contaminated samples in not only F. tularensis but also other bacteria.",2019 Nov 14,"['Azaki, Mika', 'Uda, Akihiko', 'Tian, Deyu', 'Nakazato, Katsuyoshi', 'Hotta, Akitoyo', 'Kawai, Yasuhiro', 'Ishijima, Keita', 'Kuroda, Yudai', 'Maeda, Ken', 'Morikawa, Shigeru']",PLoS One,,,True
025509677d6507aaf63c46fc8efbe60b6d63a820,PMC,Subclinical in utero Zika virus infection is associated with interferon alpha sequelae and sex-specific molecular brain pathology in asymptomatic porcine offspring,http://dx.doi.org/10.1371/journal.ppat.1008038,PMC6855438,31725819,CC BY,"Zika virus (ZIKV) infection during human pregnancy may lead to severe fetal pathology and debilitating impairments in offspring. However, the majority of infections are subclinical and not associated with evident birth defects. Potentially detrimental life-long health outcomes in asymptomatic offspring evoke high concerns. Thus, animal models addressing sequelae in offspring may provide valuable information. To induce subclinical infection, we inoculated selected porcine fetuses at the mid-stage of development. Inoculation resulted in trans-fetal virus spread and persistent infection in the placenta and fetal membranes for two months. Offspring did not show congenital Zika syndrome (e.g., microcephaly, brain calcifications, congenital clubfoot, arthrogryposis, seizures) or other visible birth defects. However, a month after birth, a portion of offspring exhibited excessive interferon alpha (IFN-α) levels in blood plasma in a regular environment. Most affected offspring also showed dramatic IFN-α shutdown during social stress providing the first evidence for the cumulative impact of prenatal ZIKV exposure and postnatal environmental insult. Other eleven cytokines tested before and after stress were not altered suggesting the specific IFN-α pathology. While brains from offspring did not have histopathology, lesions, and ZIKV, the whole genome expression analysis of the prefrontal cortex revealed profound sex-specific transcriptional changes that most probably was the result of subclinical in utero infection. RNA-seq analysis in the placenta persistently infected with ZIKV provided independent support for the sex-specific pattern of in utero-acquired transcriptional responses. Collectively, our results provide strong evidence that two hallmarks of fetal ZIKV infection, altered type I IFN response and molecular brain pathology can persist after birth in offspring in the absence of congenital Zika syndrome.",2019 Nov 14,"['Trus, Ivan', 'Udenze, Daniel', 'Cox, Brian', 'Berube, Nathalie', 'Nordquist, Rebecca E.', 'van der Staay, Franz Josef', 'Huang, Yanyun', 'Kobinger, Gary', 'Safronetz, David', 'Gerdts, Volker', 'Karniychuk, Uladzimir']",PLoS Pathog,,,True
9ade0372676abdf2b9bcc87c5d924bc945be0a92,PMC,"Genome Sequences of Human Coronavirus OC43 and NL63, Associated with Respiratory Infections in Kilifi, Kenya",http://dx.doi.org/10.1128/MRA.00730-19,PMC6856263,31727697,CC BY,"Coding-complete genomes of two human coronavirus OC43 strains and one NL63 strain were obtained by metagenomic sequencing of clinical samples collected in 2017 and 2018 in Kilifi, Kenya. Maximum likelihood phylogenies showed that the OC43 strains were genetically dissimilar and that the NL63 strain was closely related to NL63 genotype B viruses.",2019 Nov 14,"['Kamau, Everlyn', 'Luka, Martha M.', 'de Laurent, Zaydah R.', 'Adema, Irene', 'Agoti, Charles N.', 'Nokes, D. James']",Microbiol Resour Announc,,,True
3e9d0220802e3e3fba0b25f1e2cd46b9412c4317,PMC,CLEC4M is associated with poor prognosis and promotes cisplatin resistance in NSCLC patients,http://dx.doi.org/10.7150/jca.30139,PMC6856750,31772670,CC BY,"Cisplatin-based chemotherapy is the foundation of treatment for major non-small cell lung cancer (NSCLC) patients. However, cisplatin resistance is still a challenging issue, and the molecular mechanisms underlying this resistance remain to be fully explored. CLEC4M, a Ca(2+)-dependent C-type lectin, has recently been found to correlate with tumourigenesis. This study mainly focused on whether CLEC4M impacts clinical prognosis and how CLEC4M contributes to cisplatin resistance in NSCLC. Our results found that CLEC4M was correlated with poor prognosis in patients with lung cancer. In addition, a positive association between CLEC4M expression and the IC50 values of cisplatin was found, which suggests that CLEC4M may impact cisplatin sensitivity. In vitro results from cultured A549 and H1299 cells confirmed that CLEC4M could enhance cisplatin resistance, while CLEC4M knockdown led to higher sensitivity to cisplatin in these cells. Further experiments showed that the underlying mechanisms included inhibition of cisplatin-induced cell apoptosis by CLEC4M and improved DNA repair capacity by upregulating XPA and ERCC1 expression. In addition, CLEC4M was able to promote cell migration with or without cisplatin treatment. Collectively, these findings suggest the potential clinical significance of CLEC4M inhibition in overcoming cisplatin resistance in NSCLC patients.",2019 Oct 19,"['Tan, Li-Ming', 'Li, Xi', 'Qiu, Cheng-Feng', 'Zhu, Tao', 'Hu, Cheng-Ping', 'Yin, Ji-Ye', 'Zhang, Wei', 'Zhou, Hong-Hao', 'Liu, Zhao-Qian']",J Cancer,,,True
ae55b8ea5dd2bf957694f5dc1317addb5087433a,PMC,CLEC4M is associated with poor prognosis and promotes cisplatin resistance in NSCLC patients,http://dx.doi.org/10.7150/jca.30139,PMC6856750,31772670,CC BY,"Cisplatin-based chemotherapy is the foundation of treatment for major non-small cell lung cancer (NSCLC) patients. However, cisplatin resistance is still a challenging issue, and the molecular mechanisms underlying this resistance remain to be fully explored. CLEC4M, a Ca(2+)-dependent C-type lectin, has recently been found to correlate with tumourigenesis. This study mainly focused on whether CLEC4M impacts clinical prognosis and how CLEC4M contributes to cisplatin resistance in NSCLC. Our results found that CLEC4M was correlated with poor prognosis in patients with lung cancer. In addition, a positive association between CLEC4M expression and the IC50 values of cisplatin was found, which suggests that CLEC4M may impact cisplatin sensitivity. In vitro results from cultured A549 and H1299 cells confirmed that CLEC4M could enhance cisplatin resistance, while CLEC4M knockdown led to higher sensitivity to cisplatin in these cells. Further experiments showed that the underlying mechanisms included inhibition of cisplatin-induced cell apoptosis by CLEC4M and improved DNA repair capacity by upregulating XPA and ERCC1 expression. In addition, CLEC4M was able to promote cell migration with or without cisplatin treatment. Collectively, these findings suggest the potential clinical significance of CLEC4M inhibition in overcoming cisplatin resistance in NSCLC patients.",2019 Oct 19,"['Tan, Li-Ming', 'Li, Xi', 'Qiu, Cheng-Feng', 'Zhu, Tao', 'Hu, Cheng-Ping', 'Yin, Ji-Ye', 'Zhang, Wei', 'Zhou, Hong-Hao', 'Liu, Zhao-Qian']",J Cancer,,,False
74c245d5a0275629dce204354579d47071dffb85,PMC,"The global burden of premature mortality due to the Middle East respiratory syndrome (MERS) using standard expected years of life lost, 2012 to 2019",http://dx.doi.org/10.1186/s12889-019-7899-2,PMC6857218,31727042,CC BY,"BACKGROUND: It has been 8 years since the first case of Middle East respiratory syndrome coronavirus (MERS-CoV) was reported in Saudi Arabia and the disease is still being reported in 27 countries; however, there is no international study to estimate the overall burden related of this emerging infectious disease. The present study was conducted to assess the burden of premature mortality due to Middle East respiratory syndrome (MERS) worldwide. METHODS: In this retrospective analysis, we have utilized publicly available data from the WHO website related to 1789 MERS patients reported between September 23, 2012 and May 17, 2019. To calculate the standard expected years of life lost (SEYLL), life expectancy at birth was set according to the 2000 global burden of disease study on levels 25 and 26 of West model life tables from Coale-Demeny at 82.5 and 80 years for females and males, respectively. RESULTS: Overall, the total SEYLL in males and females was 10,702 and 3817.5 years, respectively. The MERS patients within the age range of 30–59 year-olds had the highest SEYLL (8305.5 years) in comparison to the patients within the age groups 0–29 (SEYLL = 3744.5 years) and ≥ 60 years (SEYLL = 2466.5 years). The total SEYLL in all age groups in 2012, 2013, 2014, 2015, 2016, 2017, 2018, and 2019 were 71.5, 2006.5, 3162, 4425.5, 1809.5, 878, 1257.5 and 909 years, respectively. The most SEYLL related to MERS-CoV infection was in the early four years of the onset of the pandemic (2012 to 2015) and in the last four years of the MERS-CoV pandemic (216 to 2019), a significant reduction was observed in the SEYLL related to MERS-CoV infection in the MERS patients. CONCLUSION: We believe that the findings of this study will shed light about the burden of premature mortality due to MERS infection in the world and the results may provide necessary information for policy-makers to prevent, control, and make a quick response to the outbreak of MERS-CoV disease.",2019 Nov 14,"['Salamatbakhsh, Maryam', 'Mobaraki, Kazhal', 'Sadeghimohammadi, Sara', 'Ahmadzadeh, Jamal']",BMC Public Health,,,True
18f16a7deabb66575691925b8648999c01a3f21e,PMC,Rhesus Theta Defensin 1 Promotes Long Term Survival in Systemic Candidiasis by Host Directed Mechanisms,http://dx.doi.org/10.1038/s41598-019-53402-z,PMC6858451,31729441,CC BY,"Invasive candidiasis is an increasingly frequent cause of serious and often fatal infections in hospitalized and immunosuppressed patients. Mortality rates associated with these infections have risen sharply due to the emergence of multidrug resistant (MDR) strains of C. albicans and other Candida spp., highlighting the urgent need of new antifungal therapies. Rhesus theta (θ) defensin-1 (RTD-1), a natural macrocyclic antimicrobial peptide, was recently shown to be rapidly fungicidal against clinical isolates of MDR C. albicans in vitro. Here we found that RTD-1 was rapidly fungicidal against blastospores of fluconazole/caspofungin resistant C. albicans strains, and was active against established C. albicans biofilms in vitro. In vivo, systemic administration of RTD-1, initiated at the time of infection or 24 h post-infection, promoted long term survival in candidemic mice whether infected with drug-sensitive or MDR strains of C. albicans. RTD-1 induced an early (4 h post treatment) increase in neutrophils in naive and infected mice. In vivo efficacy was associated with fungal clearance, restoration of dysregulated inflammatory cytokines including TNF-α, IL-1β, IL-6, IL-10, and IL-17, and homeostatic reduction in numbers of circulating neutrophils and monocytes. Because these effects occurred using peptide doses that produced maximal plasma concentrations (Cmax) of less than 1% of RTD-1 levels required for in vitro antifungal activity in 50% mouse serum, while inducing a transient neutrophilia, we suggest that RTD-1 mediates its antifungal effects in vivo by host directed mechanisms rather than direct fungicidal activity. Results of this study suggest that θ-defensins represent a new class of host-directed compounds for treatment of disseminated candidiasis.",2019 Nov 15,"['Basso, Virginia', 'Tran, Dat Q.', 'Schaal, Justin B.', 'Tran, Patti', 'Eriguchi, Yoshihiro', 'Ngole, Diana', 'Cabebe, Anthony E.', 'Park, A. young', 'Beringer, Paul M.', 'Ouellette, André J.', 'Selsted, Michael E.']",Sci Rep,,,False
eb289af3995ebdf5654f8553444b4dbc6ca30667,PMC,Rhesus Theta Defensin 1 Promotes Long Term Survival in Systemic Candidiasis by Host Directed Mechanisms,http://dx.doi.org/10.1038/s41598-019-53402-z,PMC6858451,31729441,CC BY,"Invasive candidiasis is an increasingly frequent cause of serious and often fatal infections in hospitalized and immunosuppressed patients. Mortality rates associated with these infections have risen sharply due to the emergence of multidrug resistant (MDR) strains of C. albicans and other Candida spp., highlighting the urgent need of new antifungal therapies. Rhesus theta (θ) defensin-1 (RTD-1), a natural macrocyclic antimicrobial peptide, was recently shown to be rapidly fungicidal against clinical isolates of MDR C. albicans in vitro. Here we found that RTD-1 was rapidly fungicidal against blastospores of fluconazole/caspofungin resistant C. albicans strains, and was active against established C. albicans biofilms in vitro. In vivo, systemic administration of RTD-1, initiated at the time of infection or 24 h post-infection, promoted long term survival in candidemic mice whether infected with drug-sensitive or MDR strains of C. albicans. RTD-1 induced an early (4 h post treatment) increase in neutrophils in naive and infected mice. In vivo efficacy was associated with fungal clearance, restoration of dysregulated inflammatory cytokines including TNF-α, IL-1β, IL-6, IL-10, and IL-17, and homeostatic reduction in numbers of circulating neutrophils and monocytes. Because these effects occurred using peptide doses that produced maximal plasma concentrations (Cmax) of less than 1% of RTD-1 levels required for in vitro antifungal activity in 50% mouse serum, while inducing a transient neutrophilia, we suggest that RTD-1 mediates its antifungal effects in vivo by host directed mechanisms rather than direct fungicidal activity. Results of this study suggest that θ-defensins represent a new class of host-directed compounds for treatment of disseminated candidiasis.",2019 Nov 15,"['Basso, Virginia', 'Tran, Dat Q.', 'Schaal, Justin B.', 'Tran, Patti', 'Eriguchi, Yoshihiro', 'Ngole, Diana', 'Cabebe, Anthony E.', 'Park, A. young', 'Beringer, Paul M.', 'Ouellette, André J.', 'Selsted, Michael E.']",Sci Rep,,,True
347f19fee8147e17a853627c99decbeada4660dc,PMC,"Paramyxoviruses respiratory syncytial virus, parainfluenza virus, and human metapneumovirus infection in pediatric hospitalized patients and climate correlation in a subtropical region of southern China: a 7-year survey",http://dx.doi.org/10.1007/s10096-019-03693-x,PMC6858468,31489496,CC BY,"To investigate the features of paramyxovirus respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (HMPV) infection and determine the effect of meteorological conditions in Guangzhou, a subtropical region of southern China. We collected 11,398 respiratory samples from hospitalized pediatric patients with acute respiratory illness between July 2009 and June 2016 in Guangzhou. The samples were tested simultaneously for 18 respiratory pathogens using real-time PCR. Local meteorological data were also collected for correlation analysis. Of 11,398 patients tested, 5606 (49.2%) patients tested positive for one or more pathogens; RSV, PIV, and HMPV were the first, sixth, and ninth most frequently detected pathogens, in 1690 (14.8%), 502 (4.4%), and 321 (2.8%) patients, respectively. A total 17.9% (4605/5606) of patients with positive results had coinfection with other pathogens. Significant differences were found in the prevalence of RSV, PIV, and HMPV among all age groups (p < 0.001). RSV and HMPV had similar seasonal patterns, with two prevalence peaks every year. PIV appeared alternatively with RSV and HMPV. Multiple linear regression models were established for RSV, PIV, and HMPV prevalence and meteorological factors (p < 0.05). RSV and PIV incidence was negatively correlated with monthly mean relative humidity; RSV and HMPV incidence was negatively correlated with sunshine duration; PIV incidence was positively correlated with mean temperature. We described the features of paramyxovirus infection in a subtropical region of China and highlighted the correlation with meteorological factors. These findings will assist public health authorities and clinicians in improving strategies for controlling paramyxovirus infection.",2019 Sep 5,"['Liu, Wen-Kuan', 'Chen, De-Hui', 'Tan, Wei-Ping', 'Qiu, Shu-Yan', 'Xu, Duo', 'Zhang, Li', 'Gu, Shu-Jun', 'Zhou, Rong', 'Liu, Qian']",Eur J Clin Microbiol Infect Dis,,,True
f6610246f9b5c9535a4ad4e96fa4bee87624cbc1,PMC,Pseudomonas aeruginosa lectin LecB impairs keratinocyte fitness by abrogating growth factor signalling,http://dx.doi.org/10.26508/lsa.201900422,PMC6858607,31732693,CC BY,"Lectins are glycan-binding proteins with no catalytic activity and ubiquitously expressed in nature. Numerous bacteria use lectins to efficiently bind to epithelia, thus facilitating tissue colonisation. Wounded skin is one of the preferred niches for Pseudomonas aeruginosa, which has developed diverse strategies to impair tissue repair processes and promote infection. Here, we analyse the effect of the P. aeruginosa fucose-binding lectin LecB on human keratinocytes and demonstrate that it triggers events in the host, upon binding to fucosylated residues on cell membrane receptors, which extend beyond its role as an adhesion molecule. We found that LecB associates with insulin-like growth factor-1 receptor and dampens its signalling, leading to the arrest of cell cycle. In addition, we describe a novel LecB-triggered mechanism to down-regulate host cell receptors by showing that LecB leads to insulin-like growth factor-1 receptor internalisation and subsequent missorting towards intracellular endosomal compartments, without receptor activation. Overall, these data highlight that LecB is a multitask virulence factor that, through subversion of several host pathways, has a profound impact on keratinocyte proliferation and survival.",2019 Nov 15,"['Landi, Alessia', 'Mari, Muriel', 'Kleiser, Svenja', 'Wolf, Tobias', 'Gretzmeier, Christine', 'Wilhelm, Isabel', 'Kiritsi, Dimitra', 'Thünauer, Roland', 'Geiger, Roger', 'Nyström, Alexander', 'Reggiori, Fulvio', 'Claudinon, Julie', 'Römer, Winfried']",Life Sci Alliance,,,True
082892d44934e61adfef5cd6d5867439e30b183b,PMC,Pseudomonas aeruginosa lectin LecB impairs keratinocyte fitness by abrogating growth factor signalling,http://dx.doi.org/10.26508/lsa.201900422,PMC6858607,31732693,CC BY,"Lectins are glycan-binding proteins with no catalytic activity and ubiquitously expressed in nature. Numerous bacteria use lectins to efficiently bind to epithelia, thus facilitating tissue colonisation. Wounded skin is one of the preferred niches for Pseudomonas aeruginosa, which has developed diverse strategies to impair tissue repair processes and promote infection. Here, we analyse the effect of the P. aeruginosa fucose-binding lectin LecB on human keratinocytes and demonstrate that it triggers events in the host, upon binding to fucosylated residues on cell membrane receptors, which extend beyond its role as an adhesion molecule. We found that LecB associates with insulin-like growth factor-1 receptor and dampens its signalling, leading to the arrest of cell cycle. In addition, we describe a novel LecB-triggered mechanism to down-regulate host cell receptors by showing that LecB leads to insulin-like growth factor-1 receptor internalisation and subsequent missorting towards intracellular endosomal compartments, without receptor activation. Overall, these data highlight that LecB is a multitask virulence factor that, through subversion of several host pathways, has a profound impact on keratinocyte proliferation and survival.",2019 Nov 15,"['Landi, Alessia', 'Mari, Muriel', 'Kleiser, Svenja', 'Wolf, Tobias', 'Gretzmeier, Christine', 'Wilhelm, Isabel', 'Kiritsi, Dimitra', 'Thünauer, Roland', 'Geiger, Roger', 'Nyström, Alexander', 'Reggiori, Fulvio', 'Claudinon, Julie', 'Römer, Winfried']",Life Sci Alliance,,,True
7fd8ed092a2b2e87a796cc59ccf3f7122c05fd44,PMC,Classical Swine Fever Virus Infection Induces Endoplasmic Reticulum Stress-Mediated Autophagy to Sustain Viral Replication in vivo and in vitro,http://dx.doi.org/10.3389/fmicb.2019.02545,PMC6861840,31798542,CC BY,"Endoplasmic reticulum (ER) stress-mediated autophagy plays significant roles in replication and pathogenesis of many animal viruses. However, the relationship between ER stress, autophagy, and viral replication during in vivo and in vitro infection of classical swine fever virus (CSFV) remains unclear. In this study, we established a pig model for CSFV infection and found that viral loads of CSFV differed in 10 kinds of infected organs, and that the degree of tissue lesions was to some extent positively correlated with CSFV replication in vivo. Next, we found that CSFV infection not only induced ER stress and subsequently activated three unfolded protein responses (UPR) pathways including protein kinase R-like ER kinase (PERK), inositol requiring enzyme 1 (IRE1), and activating transcription factor-6 (ATF-6) pathways, but also triggered complete autophagy in main immune organs and partial nonimmune organs exhibiting severer pathological injuries and higher viral loads. However, only the IRE1 pathway and no autophagy were activated in some other nonimmune organs with slighter pathologies and lower viral loads. These results indicate a potential link between CSFV-induced ER stress and autophagy, both of which are associated with the CSFV replication in vivo. We further performed in vitro experiments and found that CSFV infection activates the PERK and IRE1 pathways and autophagy in cultured porcine kidney cell lines (PK-15) and macrophage cell lines (3D4/2), and pharmacological regulation of ER stress remarkably changed autophagic activities induced by CSFV, suggesting that CSFV-induced autophagy can be mediated by ER stress possibly via the PERK and IRE1 pathway. Furthermore, treatment with ER stress regulators significantly altered copy numbers of NS5B genes, expression of Npro proteins, and viral titers in CSFV-infected cells or in cells treated with autophagy regulators prior to CSFV infection, suggesting the requirement of ER stress-mediated autophagy for CSFV replication in vitro. Collectively, our data demonstrate that CSFV induces ER stress-mediated autophagy to sustain its replication in vivo and in vitro, which may be one of the potential strategies exploited by CSFV for immune evasion. This finding will provide new insights into mechanisms of replication and pathogenesis of CSFV, and development of new strategies for controlling CSF.",2019 Nov 12,"['Zhu, Erpeng', 'Chen, Wenxian', 'Qin, Yuwei', 'Ma, Shengming', 'Fan, Shuangqi', 'Wu, Keke', 'Li, Wenhui', 'Fan, Jindai', 'Yi, Lin', 'Ding, Hongxing', 'Chen, Jinding', 'Zhao, Mingqiu']",Front Microbiol,,,True
87cc7c4ce4f857e235f5fe0fffc2513cf9e653d9,PMC,Emerging Highly Virulent Porcine Epidemic Diarrhea Virus: Molecular Mechanisms of Attenuation and Rational Design of Live Attenuated Vaccines,http://dx.doi.org/10.3390/ijms20215478,PMC6862049,31689903,CC BY,"The highly virulent porcine epidemic diarrhea virus (PEDV) emerged in China in 2010. It infects pigs of all ages, and causes severe diarrhea and high mortality rates in newborn pigs, leading to devastating economic losses in the pork industry worldwide. Effective and safe vaccines against highly virulent PEDV strains are still unavailable, hampering the further prevention, control and eradication of the disease in herds. Vaccination of pregnant sows with live attenuated vaccines (LAVs) is the most effective strategy to induce lactogenic immunity in the sows, which provides A passive protection of suckling piglets against PEDV via the colostrum (beestings, or first milk) and milk. Several LAV candidates have been developed via serially passaging the highly virulent PEDV isolates in non-porcine Vero cells. However, their efficacies in the induction of sufficient protection against virulent PEDV challenge vary in vivo. In this review, we summarize the current knowledge of the virulence-related mutations of PEDV and their potential roles in PEDV attenuation in vivo. With the successful development of reverse genetics systems for PEDV, we also discuss how to use them to generate promising LAV candidates that are safe, effective and genetically stable. This article provides timely insight into the rational design of effective and safe PEDV LAV candidates.",2019 Nov 4,"['Hou, Yixuan', 'Wang, Qiuhong']",Int J Mol Sci,,,True
75e12afbacd0c6dcdb20697a093ed0835e9bbead,PMC,Microglia Are Essential to Protective Antiviral Immunity: Lessons From Mouse Models of Viral Encephalitis,http://dx.doi.org/10.3389/fimmu.2019.02656,PMC6863772,31798586,CC BY,"Viral encephalitis is a rare but clinically serious consequence of viral invasion of the brain and insight into its pathogenesis is urgently needed. Important research questions concern the involvement of the host innate immune response in pathogenesis, key to which is the role played by microglia, resident macrophages of the brain parenchyma. Do microglia have a protective function, by coordinating the innate immune response to viral infection, or do they drive pathogenic neuroinflammation? Here we synthesize recent data from mouse models of acute viral encephalitis, which reveal an unambiguously protective role for microglia. Depletion of microglia, via blockade of colony-stimulating factor 1 receptor (CSF1R) signaling, led to increased viral replication accompanied by more severe neurological disease and heightened mortality. Whilst the underlying mechanism(s) remain to be defined, microglial interactions with T cells and phagocytosis of infected neurones appear to play a role. Paradoxically, the production of inflammatory cytokines was increased in several instances following viral infection in microglia-depleted brains, suggesting that: (i) cells other than microglia mediate inflammatory responses and/or (ii) microglia may exert a regulatory function. Under certain circumstances the microglial antiviral response might contribute negatively to longer-term neurological sequelae, although fewer studies have focused on this aspect in encephalitis models. Understanding regulation of the microglial response, and how it contributes to disease is therefore a priority for future studies. Collectively, these findings demonstrate the central role of microglia in pathogenesis, suggesting the exciting possibility that defects of microglial function might contribute to encephalitis susceptibility and/or outcome in humans.",2019 Nov 13,"['Hatton, Catherine F.', 'Duncan, Christopher J. A.']",Front Immunol,,,True
e8d7fb48d727d602587af256f10d5b389af1d7a1,PMC,"Synthetic, Structural, and Anticancer Activity Evaluation Studies on Novel Pyrazolylnucleosides",http://dx.doi.org/10.3390/molecules24213922,PMC6864788,31671703,CC BY,"The synthesis of novel pyrazolylnucleosides 3a–e, 4a–e, 5a–e, and 6a–e are described. The structures of the regioisomers were elucidated by using extensive NMR studies. The pyrazolylnucleosides 5a–e and 6a–e were screened for anticancer activities on sixty human tumor cell lines. The compound 6e showed good activity against 39 cancer cell lines. In particular, it showed significant inhibition against the lung cancer cell line Hop-92 (GI(50) 9.3 µM) and breast cancer cell line HS 578T (GI(50) 3.0 µM).",2019 Oct 30,"['Yadav, Yogesh', 'Sharma, Deepti', 'Kaushik, Kumar', 'Kumar, Vineet', 'Jha, Amitabh', 'Prasad, Ashok K.', 'Len, Christophe', 'Malhotra, Sanjay V.', 'Wengel, Jesper', 'Parmar, Virinder S.']",Molecules,,,True
b71acc02a9c8dfe1b85de4fa2eb33c10069c5556,PMC,"Synthetic, Structural, and Anticancer Activity Evaluation Studies on Novel Pyrazolylnucleosides",http://dx.doi.org/10.3390/molecules24213922,PMC6864788,31671703,CC BY,"The synthesis of novel pyrazolylnucleosides 3a–e, 4a–e, 5a–e, and 6a–e are described. The structures of the regioisomers were elucidated by using extensive NMR studies. The pyrazolylnucleosides 5a–e and 6a–e were screened for anticancer activities on sixty human tumor cell lines. The compound 6e showed good activity against 39 cancer cell lines. In particular, it showed significant inhibition against the lung cancer cell line Hop-92 (GI(50) 9.3 µM) and breast cancer cell line HS 578T (GI(50) 3.0 µM).",2019 Oct 30,"['Yadav, Yogesh', 'Sharma, Deepti', 'Kaushik, Kumar', 'Kumar, Vineet', 'Jha, Amitabh', 'Prasad, Ashok K.', 'Len, Christophe', 'Malhotra, Sanjay V.', 'Wengel, Jesper', 'Parmar, Virinder S.']",Molecules,,,False
8ad769c159358842b5ccacbd383987335844ad86,PMC,Factors Associated With Measles Transmission in the United States During the Postelimination Era,http://dx.doi.org/10.1001/jamapediatrics.2019.4357,PMC6865326,31738391,CC BY,"IMPORTANCE: Measles cases and outbreaks continue to occur in the United States after the introduction of measles from endemic settings. OBJECTIVE: To discern the factors associated with measles transmission in the United States after measles had been eliminated. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted from January 1, 2001, to December 31, 2017, in the United States among US residents and international visitors with confirmed measles. A maximum likelihood algorithm that uses the observed dates of rash onset and the known distribution of the serial interval (time between symptom onset in related consecutive cases) was applied to outbreak notification data to estimate the effective reproduction number (R), or the mean number of new infections generated per case. Transmissibility was assessed by comparing R based on the characteristics of primary and secondary cases of measles. EXPOSURES: Measles virus. MAIN OUTCOMES AND MEASURES: Effective reproduction number (R), or the mean number of successful transmission events per case of measles (ie, the mean number of persons to whom each patient with measles spreads measles). RESULTS: A total of 2218 individuals with confirmed measles cases (1025 female, 1176 male, and 17 sex not reported; median age, 15 years [range, 0-89 years]) reported from 2001 to 2017 were evaluated. Among patients who received no doses of measles vaccine, R was 0.76 (95% CI, 0.71-0.81); among patients who received 1 dose of measles vaccine, R was 0.17 (95% CI, 0.11-0.26); among patients who received 2 doses or more of measles vaccine, R was 0.27 (95% CI, 0.17-0.39); and among patients with unknown vaccination status, R was 0.52 (95% CI, 0.44-0.60). Among patients born before 1957, R was 0.35 (95% CI, 0.20-0.58), and among those born on or after 1957, R was 0.64 (95% CI, 0.61-0.68). R was higher when primary and secondary cases of measles were patients aged 5 to 17 years (0.36 [95% CI, 0.31-0.42]) compared with assortative transmission in other age groups (<1 year, 0.14 [95% CI, 0.10-0.20]; 1-4 years, 0.25 [95% CI, 0.20-0.30]; 18-29 years, 0.19 [95% CI, 0.15-0.24]; 30-49 years, 0.15 [95% CI, 0.11-0.20]; ≥50 years, 0.04 [95% CI, 0.01-0.10]). CONCLUSIONS AND RELEVANCE: The findings of this study support having high targets for 2-dose measles vaccine coverage, particularly among school-aged children in the United States.",2020 Jan 18,"['Gastañaduy, Paul A.', 'Funk, Sebastian', 'Lopman, Benjamin A.', 'Rota, Paul A.', 'Gambhir, Manoj', 'Grenfell, Bryan', 'Paul, Prabasaj']",JAMA Pediatr,,,True
3c9db7ee30074667f9fe308de9910b013aa1f163,PMC,Recombinant adenoviral vaccine encoding the spike 1 subunit of the Middle East Respiratory Syndrome Coronavirus elicits strong humoral and cellular immune responses in mice,http://dx.doi.org/10.14202/vetworld.2019.1554-1562,PMC6868266,31849416,CC BY,"BACKGROUND AND AIM: Middle East respiratory syndrome coronavirus (MERS-CoV) has rapidly spread throughout the Middle East since its discovery in 2012. The virus poses a significant global public health threat with potentially devastating effects. In this study, a recombinant adenoviral-based vaccine encoding the spike 1 (S1) subunit of the MERS-CoV genome was constructed, and its humoral, and cellular immune responses were evaluated in mice. MATERIALS AND METHODS: Mice were immunized initially by intramuscular injection and boosted 3 weeks later by intranasal application. Expression of the S1 protein in the lungs and kidneys was detected using conventional polymerase chain reaction (PCR) and immunohistochemistry (IHC) targeting specific regions within the S1 subunit at weeks 3, 4, 5, and 6 after the first vaccination. Antigen-specific humoral and cellular immune responses were evaluated in serum and in cell culture following in vitro stimulation with a specific 9-mer epitope within the S1 protein (CYSSLILDY). RESULTS: S1 protein expression was only detected by IHC in the kidneys of the Ad-MERS-S1 group at week 6 from first immunization, and in both lungs and kidneys of Ad-MERS-S1 group by conventional PCR at weeks 3 and 5 post-prime. The vaccine elicited a specific S1-immunoglobulin G antibody response, which was detected in the sera of the vaccinated mice at weeks 4 and 6 from the onset of the first immunization. There was a significant increase in the amount of Th1-related cytokines (interferon-γ and interleukin [IL] 12), and a significant decrease in the Th2-related cytokine IL-4 in splenocyte cell culture of the vaccinated group compared with the control groups. CONCLUSION: The results of this study suggest that this recombinant adenovirus vaccine encoding the S1 subunit of MERS-CoV elicits potentially protective antigen-specific humoral and cellular immune responses in mice. This study demonstrates a promising vaccine for the control and/or prevention of MERS-CoV infection in humans.",2019 Oct 11,"['Ababneh, Mustafa', 'Alrwashdeh, Mu’men', 'Khalifeh, Mohammad']",Vet World,,,True
74d95e321596279f3e8fcf1ad1f04508f48552e2,PMC,Procalcitonin as a prognostic marker for sepsis based on SEPSIS‐3,http://dx.doi.org/10.1002/jcla.22996,PMC6868407,31420921,CC BY,"BACKGROUND: The revised definition of sepsis is life‐threatening organ dysfunction caused by a dysregulated host response to infection (SEPSIS‐3). The objective of this study was to evaluate procalcitonin (PCT) for the diagnosis and prognosis of sepsis using SEPSIS‐3. METHODS: We enrolled 248 patients, who were admitted to the emergency department with suspected bacterial infection from June 2016 to February 2017. Definite bacterial infection was defined by proven culture results, and probable bacterial infection was based on diagnostic modalities other than culture. The sequential organ failure assessment (SOFA) score of 2 points or more from the baseline was diagnosed as sepsis. PCT was measured by the AFIAS‐6 immunoassay system (Boditech Med Inc.) using whole blood. White blood cell (WBC), C‐reactive protein (CRP), and erythrocyte sedimentation rate (ERS) were evaluated. RESULTS: The final diagnosis was sepsis in 185 patients with infection of respiratory and genitourinary tract constituted 84.6%. The area under the receiver operating characteristic curve (AUROC) with 95% confidence interval (CI) was as follows: PCT, 0.682 (0.589‐0.765); CRP, 0.583 (0.487‐0.673); ESR, 0.540 (0.515‐0.699); and WBC, 0.611 (0.455‐0.633), respectively. In multivariate analysis, age, SOFA, and PCT (log scale) predicted non‐survivors with an odds ratio with 95% confidence interval of 1.055 (1.008‐1.105), 1.303 (1.142‐1.486), and 2.004 (1.240‐3.238), respectively. Among sepsis group, initial PCT was increased in non‐survivor (23.2 ng/dL) compared to survivor group (8.1 ng/dL) with statistical significance (P = .005). CONCLUSIONS: PCT could support and predict the unfavorable prognosis of sepsis based on SEPSIS‐3, whereas diagnostic potential of PCT requires further evaluations.",2019 Aug 16,"['Jekarl, Dong Wook', 'Lee, Seungok', 'Kim, Myungshin', 'Kim, Yonggoo', 'Woo, Seon Hee', 'Lee, Woon Jeong']",J Clin Lab Anal,,,True
fa137f1562d599f03605b83bc68f91e5105110d9,PMC,Pharmacological plasticity—How do you hit a moving target?,http://dx.doi.org/10.1002/prp2.532,PMC6868654,31768257,CC BY,"Paul Ehrlich's concept of the magic bullet, by which a single drug induces pharmacological effects by interacting with a single receptor has been a strong driving force in pharmacology for a century. It is continually thwarted, though, by the fact that the treated organism is highly dynamic and the target molecule(s) is (are) never static. In this article, we address some of the factors that modify and cause the mobility and plasticity of drug targets and their interactions with ligands and discuss how these can lead to unexpected (lack of) effects of drugs. These factors include genetic, epigenetic, and phenotypic variability, cellular plasticity, chronobiological rhythms, time, age and disease resolution, sex, drug metabolism, and distribution. We emphasize four existing approaches that can be taken, either singly or in combination, to try to minimize effects of pharmacological plasticity. These are firstly, to enhance specificity using target conditions close to those in diseases, secondly, by simultaneously or thirdly, sequentially aiming at multiple targets, and fourthly, in synchronization with concurrent dietary, psychological, training, and biorhythm‐synchronizing procedures to optimize drug therapy.",2019 Nov 21,"['Parnham, Michael J.', 'Geisslinger, Gerd']",Pharmacol Res Perspect,,,True
c25e535e8cb1fa2ff9e24c6e582d261d09551632,PMC,Melatonin is responsible for rice resistance to rice stripe virus infection through a nitric oxide-dependent pathway,http://dx.doi.org/10.1186/s12985-019-1228-3,PMC6869260,31752902,CC BY,"Rice stripe virus (RSV) causes one of the most important rice virus diseases of plants in East Asia. However, the molecular mechanisms controlling rice resistance to RSV infection are largely unknown. Recently, several studies presented a novel model that melatonin (MT) and nitric oxide (NO) participate in the plant-pathogen interaction in a synergetic manner. In this study, there was a difference in MT content between two rice varieties that correlated with one being susceptible and one being resistant to RSV, which suggested that MT is related to RSV resistance. In addition, a test with two NO biosynthesis inhibitors revealed that NO inhibitor were able to increase the disease incidence of RSV. A pharmacological experiment with exogenous MT and NO showed that increased MT and NO in the MT-pretreated plants led to lower disease incidences; however, only NO increased in a NO-releasing reagent [sodium nitroprusside (SNP)] pretreated plants. The expressions level of OsPR1b and OsWRKY 45 were significantly induced by MT and NO. These results suggest that rice resistance to RSV can be improved by increased MT through a NO-dependent pathway.",2019 Nov 21,"['Lu, Rongfei', 'Liu, Zhiyang', 'Shao, Yudong', 'Sun, Feng', 'Zhang, Yali', 'Cui, Jin', 'Zhou, Yijun', 'Shen, Wenbiao', 'Zhou, Tong']",Virol J,,,True
bad0e9f737316570c33138d5cc95cc233cd937ab,PMC,"Molecular detection of respiratory pathogens among children aged younger than 5 years hospitalized with febrile acute respiratory infections: A prospective hospital‐based observational study in Niamey, Niger",http://dx.doi.org/10.1002/hsr2.137,PMC6869554,31768420,CC BY,"BACKGROUND AND AIMS: In Niger, acute respiratory infections (ARIs) are the second most common cause of death in children aged younger than 5 years. However, the etiology of ARI is poorly understood in the country. This study aims to describe viral and bacterial infections among children aged younger than 5 years hospitalized with febrile ARI at two hospitals in Niamey, Niger's capital city, and the reported clinical procedures. METHODS: We conducted a prospective study among children aged younger than 5 years hospitalized with febrile ARI at two national hospitals in Niamey between January and December 2015. Clinical presentation and procedures during admission were documented using a standardized case investigation form. Nasopharyngeal specimens collected from each patient were tested for a panel of respiratory viruses and bacteria using the Fast Track Diagnostic 21 Plus kit. RESULTS: We enrolled and tested 638 children aged younger than 5 years, of whom 411 (64.4%) were aged younger than 1 year, and 15 (2.4%) died during the study period. Overall, 496/638 (77.7%) specimens tested positive for at least one respiratory virus or bacterium; of these, 195 (39.3%) tested positive for respiratory viruses, 126 (25.4%) tested positive for respiratory bacteria, and 175 (35.3%) tested positive for both respiratory viruses and bacteria. The predominant viruses detected were respiratory syncytial virus (RSV) (149/638; 23.3%), human parainfluenza virus (HPIV) types 1 to 4 (78/638; 12.2%), human rhinovirus (HRV) (62/638; 9.4%), human adenovirus (HAV) (60/638; 9.4%), and influenza virus (INF) (52/638; 8.1%). Streptococcus pneumoniae (249/638; 39.0%) was the most frequently detected bacterium, followed by Staphylococcus aureus (112/638; 12.2%) and Haemophilus influenzae type B (16/638; 2.5%). Chest X‐rays were performed at the discretion of the attending physician on 301 (47.2%) case patients. Of these patients, 231 (76.7%) had abnormal radiological findings. A total of 135/638 (21.2%) and 572/638 (89.7%) children received antibiotic treatment prior to admission and during admission, respectively. CONCLUSION: A high proportion of respiratory viruses was detected among children aged younger than 5 years with febrile ARI, raising concerns about excessive use of antibiotics in Niger.",2019 Oct 11,"['Lagare, Adamou', 'Ousmane, Sani', 'Dano, Ibrahim Dan', 'Issaka, Bassira', 'Issa, Idi', 'Mainassara, Halima Boubacar', 'Testa, Jean', 'Tempia, Stefano', 'Mamadou, Saidou']",Health Sci Rep,,,True
b6277684930fa5819fe101a39441601ab89da85a,PMC,iTRAQ-based high-throughput proteomics analysis reveals alterations of plasma proteins in patients infected with human bocavirus,http://dx.doi.org/10.1371/journal.pone.0225261,PMC6872134,31751365,CC BY,"Human bocavirus (HBoV) is a member of the genus Bocavirus, family Parvoviridae, and subfamily Parvovirus and was first identified in nasopharyngeal aspirates of Swedish children with acute respiratory tract infection (ARTI) in 2005. It is the causative agent of nasopharyngeal aspirate disease and death in children. The HboV genomic structure is a linear single-stranded DNA (ssDNA). Its clinical pathogenic characteristics have been extensively studied, however, at present the molecular mechanism underlying the pathogenesis of HBoV infection is not completely clear. In this study, a total of 293 differentially expressed proteins (DEPs) between ARTI cases and healthy plasma samples were characterized using isobaric tags for relative and absolute quantitation (iTRAQ)-coupled bioinformatics analysis, among which 148 were up-regulated and 135 were down-regulated. Gene Ontology (GO) and Cluster of Orthologous Groups of proteins (COG) annotated an enrichment of DEPs in complement activation and biological processes like immunity, inflammation, signal transduction, substance synthesis, and metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis enriched DEPs mainly in the Wnt signaling pathway (ko04310), PPAR signaling pathway (ko03320), intestinal immune network for IgA production (ko04672), complement and coagulation cascades (ko04610), Toll-like receptor signaling pathway (ko04620) and B cell receptor signaling pathway (ko04662). Further, expression levels of three candidate proteins (upregulated PPP2R1A and CUL1, and downregulated CETP) were validated using western blotting. Our investigation is the first analysis of the proteomic profile of HBoV-infected ARTI cases using the iTRAQ approach, providing a foundation for a better molecular understanding of the pathogenesis of ARTI in children.",2019 Nov 21,"['Bian, Junmei', 'Liang, Min', 'Ding, Shuxian', 'Wang, Liyan', 'Ni, Wenchang', 'Xiong, Shisi', 'Li, Wan', 'Bao, Xingxing', 'Gao, Xue', 'Wang, Rong']",PLoS One,,,True
12c70c4d576fce0b20fce2b35e47b05baea97e35,PMC,Measuring inequalities in the public health workforce at county-level Centers for Disease Control and Prevention in China,http://dx.doi.org/10.1186/s12939-019-1073-4,PMC6873429,31752854,CC BY,"BACKGROUND: The public health workforce (PHW) is a key component of a country’s public health system. Since the outbreak of SARS (severe acute respiratory syndrome) in 2003, the scale of PHW in China has been continuously expanding, but policymakers and researchers still focus on the distribution of public health personnel, especially the regional inequality in such distribution. We aimed to identify the root cause of PHW inequality by decomposing different geographical units in China. METHODS: This study was based on data from a nationwide survey, which included 2712 county-level data. The distribution of the PHW in geographical units was evaluated by the Gini coefficient and Theil T index, and inequalities at regional, provincial, and municipal levels were decomposed to identify the root causes of inequalities in the PHW. Additionally, the contextual factors affecting the distribution of the PHW were determined through regression analysis. RESULTS: The overall inequality results show that health professional and field epidemiological investigators faced worse inequality than the staff. In particular, field epidemiological investigators had a Gini coefficient close to 0.4. Step decomposition showed that within-region inequalities accounted for 98.5% or more of overall inter-county inequality in the distribution of all PHW categories; provincial decomposition showed that at least 74% of inequality is still distributed within provinces; the overall contribution of within-municipal inequality and between-municipal inequality was basically the same. Further, the contextual factor that influenced between-municipality and within-municipality inequality for all three categories of PHWs was the agency building area per employee. Per capita GDP had a similar effect, except for between-municipality inequality of professionals and within-municipality inequality of field epidemiological investigators. CONCLUSIONS: The successive decomposition showed that inequality is mainly concentrated in counties at the within-province and within-municipal levels. This study clearly suggests that the government, especially the municipal government at the provincial level, should increase financial investment in Centers for Disease Control and Prevention (CDCs) with worse resource allocation in their jurisdiction through various ways of compensation and incentives, enhance their infrastructure, and improve the salary of personnel in these institutions, to attract more public health professionals to these institutions.",2019 Nov 21,"['Cai, Weiqin', 'Li, Chengyue', 'Sun, Mei', 'Hao, Mo']",Int J Equity Health,,,True
3c4505f3ce59be775697d87a10f448ac2afc7ad7,PMC,Global scientific trends on aflatoxin research during 1998–2017: a bibliometric and visualized study,http://dx.doi.org/10.1186/s12995-019-0248-7,PMC6873441,31832075,CC BY,"BACKGROUND: Aflatoxins are fungal metabolites associated with contaminated food products. Intake of aflatoxin-contaminated food results in serious health hazards and even death. Therefore, the aim of this study is to evaluate the global scientific output of research of aflatoxin by using bibliometric techniques. METHODS: This bibliometric study was conducted using Scopus database and classified the retrieved publications were classified from different aspects, including the countries/region of focus, journals, authors, institutes, citations, and content analysis to discover any hot and emerging topics. In addition, the bibliometric analysis of the international collaborative network and hot research topics were generated by VOSviewer© software version 1.6.10. The publication period was restricted in the search for two decades (1998–2017). RESULTS: The search engine of the Scopus database found 9845 documents published in the field of aflatoxin. The USA is the top publishing source in the world (22.85%), followed by China (11.85%), India (9.32%), and Italy (5.25%). In earlier years, researchers focused on terms related to the topics of “sources and biosynthesis of aflatoxin”, “health effects by aflatoxin”, and “detoxification and treatment of aflatoxin”. However, in recent years, researchers pay more attention to the topic of detection and quantification of aflatoxin. CONCLUSIONS: The quantity of research in global aflatoxin has substantially increased over the past two decades. The evaluation of the historical status and development trend in aflatoxin scientific research can guide future research, and ultimately provide the basis for improving management procedures for governmental decisions, healthcare, industries, and educational institutions.",2019 Nov 21,"Zyoud, Sa’ed H.",J Occup Med Toxicol,,,True
cbf67540b068488c423bd787d23143b5246a432d,PMC,Zinc Supplementation Promotes a Th1 Response and Improves Clinical Symptoms in Fewer Hours in Children With Pneumonia Younger Than 5 Years Old. A Randomized Controlled Clinical Trial,http://dx.doi.org/10.3389/fped.2019.00431,PMC6874056,31803694,CC BY,"Background: Pneumonia caused 704,000 deaths in children younger than 5 years in 2015. Zinc is an important micronutrient due to its role in immune function. Since 2004, WHO recommends zinc supplementation for children with diarrhea to shorten the duration and decrease severity. Zinc supplementation for children with pneumonia is controversial. Methods: A randomized controlled clinical trial was conducted, and 103 children 1 month to 5 years old with pneumonia were included. Zinc or placebo was given during hospitalization. Clinical symptoms were recorded, and a blood draw was obtained to determine serum zinc levels, lymphoproliferation, and cytokines at hospitalization and at discharge of the patient; a nasal wash was obtained to detect viral or bacterial pathogens by multiplex RT-PCR. Results: Zinc supplementation improved in fewer hours the clinical status (76 ± 7 vs. 105 ± 8, p = 0.01), the respiratory rate (37 ± 6 vs. 57 ± 7, p = 0.04), and the oxygen saturation (53 ± 7 vs. 87 ± 9, p = 0.007) compared to the placebo group. An increase in IFNγ and IL-2 after treatment in the zinc group was observed. Conclusions: Zinc supplementation improved some clinical symptoms in children with pneumonia in fewer hours and induced a cellular immune response. Clinical Trial Registration: The trial was retrospectively registered in ClinicalTrials.gov, identifier NCT03690583, URL https://clinicaltrials.gov/ct2/show/NCT03690583?term=zinc+children&cond=Pneumonia&draw=2&rank=1.",2019 Nov 14,"['Acevedo-Murillo, Jorge Alberto', 'García León, Miguel Leonardo', 'Firo-Reyes, Verónica', 'Santiago-Cordova, Jorge Luis', 'Gonzalez-Rodriguez, Alejandra Pamela', 'Wong-Chew, Rosa María']",Front Pediatr,,,True
0dfd60c077b6b77963af16759c67fe4c23559714,PMC,Zinc Supplementation Promotes a Th1 Response and Improves Clinical Symptoms in Fewer Hours in Children With Pneumonia Younger Than 5 Years Old. A Randomized Controlled Clinical Trial,http://dx.doi.org/10.3389/fped.2019.00431,PMC6874056,31803694,CC BY,"Background: Pneumonia caused 704,000 deaths in children younger than 5 years in 2015. Zinc is an important micronutrient due to its role in immune function. Since 2004, WHO recommends zinc supplementation for children with diarrhea to shorten the duration and decrease severity. Zinc supplementation for children with pneumonia is controversial. Methods: A randomized controlled clinical trial was conducted, and 103 children 1 month to 5 years old with pneumonia were included. Zinc or placebo was given during hospitalization. Clinical symptoms were recorded, and a blood draw was obtained to determine serum zinc levels, lymphoproliferation, and cytokines at hospitalization and at discharge of the patient; a nasal wash was obtained to detect viral or bacterial pathogens by multiplex RT-PCR. Results: Zinc supplementation improved in fewer hours the clinical status (76 ± 7 vs. 105 ± 8, p = 0.01), the respiratory rate (37 ± 6 vs. 57 ± 7, p = 0.04), and the oxygen saturation (53 ± 7 vs. 87 ± 9, p = 0.007) compared to the placebo group. An increase in IFNγ and IL-2 after treatment in the zinc group was observed. Conclusions: Zinc supplementation improved some clinical symptoms in children with pneumonia in fewer hours and induced a cellular immune response. Clinical Trial Registration: The trial was retrospectively registered in ClinicalTrials.gov, identifier NCT03690583, URL https://clinicaltrials.gov/ct2/show/NCT03690583?term=zinc+children&cond=Pneumonia&draw=2&rank=1.",2019 Nov 14,"['Acevedo-Murillo, Jorge Alberto', 'García León, Miguel Leonardo', 'Firo-Reyes, Verónica', 'Santiago-Cordova, Jorge Luis', 'Gonzalez-Rodriguez, Alejandra Pamela', 'Wong-Chew, Rosa María']",Front Pediatr,,,False
687da34d9c50dd79ad55b5067ffdbb7282c03d35,PMC,"NEDD4 family ubiquitin ligases associate with LCMV Z’s PPXY domain and are required for virus budding, but not via direct ubiquitination of Z",http://dx.doi.org/10.1371/journal.ppat.1008100,PMC6874086,31710650,CC BY,"Viral late domains are used by many viruses to recruit the cellular endosomal sorting complex required for transport (ESCRT) to mediate membrane scission during viral budding. Unlike the P(S/T)AP and YPX((1–3))L late domains, which interact directly with the ESCRT proteins Tsg101 and ALIX, the molecular linkage connecting the PPXY late domain to ESCRT proteins is unclear. The mammarenavirus lymphocytic choriomeningitis virus (LCMV) matrix protein, Z, contains only one late domain, PPXY. We previously found that this domain in LCMV Z, as well as the ESCRT pathway, are required for the release of defective interfering (DI) particles but not infectious virus. To better understand the molecular mechanism of ESCRT recruitment by the PPXY late domain, affinity purification-mass spectrometry was used to identify host proteins that interact with the Z proteins of the Old World mammarenaviruses LCMV and Lassa virus. Several Nedd4 family E3 ubiquitin ligases interact with these matrix proteins and in the case of LCMV Z, the interaction was PPXY-dependent. We demonstrated that these ligases directly ubiquitinate LCMV Z and mapped the specific lysine residues modified. A recombinant LCMV containing a Z that cannot be ubiquitinated maintained its ability to produce both infectious virus and DI particles, suggesting that direct ubiquitination of LCMV Z alone is insufficient for recruiting ESCRT proteins to mediate virus release. However, Nedd4 ligases appear to be important for DI particle release suggesting that ubiquitination of targets other than the Z protein itself is required for efficient viral ESCRT recruitment.",2019 Nov 11,"['Ziegler, Christopher M.', 'Dang, Loan', 'Eisenhauer, Philip', 'Kelly, Jamie A.', 'King, Benjamin R.', 'Klaus, Joseph P.', 'Manuelyan, Inessa', 'Mattice, Ethan B.', 'Shirley, David J.', 'Weir, Marion E.', 'Bruce, Emily A.', 'Ballif, Bryan A.', 'Botten, Jason']",PLoS Pathog,,,True
5909957e376b289b8aa76f7c40ac4db57084ac52,PMC,Manipulation of Intestinal Antiviral Innate Immunity and Immune Evasion Strategies of Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.1155/2019/1862531,PMC6874955,31781594,CC BY,"Porcine epidemic diarrhea virus (PEDV) infection causes watery diarrhea, dehydration, and high mortality in neonatal pigs, due to its clinical pathogenesis of the intestinal mucosal barrier dysfunction. The host's innate immune system is the first line of defence upon virus invasion of the small intestinal epithelial cells. In turn, the virus has evolved to modulate the host's innate immunity during infection, resulting in pathogen virulence, survival, and the establishment of successful infection. In this review, we gather current knowledge concerning the interplay between PEDV and components of host innate immunity, focusing on the role of cytokines and interferons in intestinal antiviral innate immunity, and the mechanisms underlying the immune evasion strategies of PEDV invasion. Finally, we provide some perspectives on the potential prevention and treatment for PEDV infection.",2019 Nov 3,"['Du, Jian', 'Luo, Junqiu', 'Yu, Jie', 'Mao, Xiangbing', 'Luo, Yuheng', 'Zheng, Ping', 'He, Jun', 'Yu, Bing', 'Chen, Daiwen']",Biomed Res Int,,,True
8c401abe39d57c49059788cdc3b95bbcceaa7d40,PMC,Medical Management of Hemorrhagic Bowel Syndrome in a Beef Bull,http://dx.doi.org/10.1155/2019/9209705,PMC6875306,31781470,CC BY,"A two and a half-year old Simmental bull was presented to Iowa State University's Food Animal and Camelid Hospital for anorexia and lethargy of several days. Clostridium perfringens type A was identified via fecal culture and toxin genotyping. Hemorrhagic bowel syndrome (HBS) was diagnosed based on microbiological results along with abdominal ultrasonography, complete blood count, and serum biochemistry. Aggressive multi-modal therapy was employed including intravenously administered fluid therapy, potassium penicillin, lidocaine, flunixin, and pantoprazole among other supportive care. The bull was discharged after 15 days of hospitalization and recovered uneventfully to full function by the next breeding season. Currently all case reports with regard to HBS in beef cattle describe mortality. While the dairy cattle literature demonstrates that HBS has a high mortality rate, and suggests that surgical intervention has a higher prognosis when compared to medical therapy in dairy cattle. Our case would provide support to aggressive medical treatment for HBS in beef cattle.",2019 Nov 3,"['Smith, Joe S.', 'Zhou, Xueying', 'Merkatoris, Paul T.', 'Klostermann, Cassandra A.', 'Breuer, Ryan M.']",Case Rep Vet Med,,,True
85bab4f8869727adbe47f5ddc6e18af508dc57a0,PMC,eIF2α-CHOP-BCl-2/JNK and IRE1α-XBP1/JNK signaling promote apoptosis and inflammation and support the proliferation of Newcastle disease virus,http://dx.doi.org/10.1038/s41419-019-2128-6,PMC6877643,31767828,CC BY,"Newcastle disease virus (NDV) causes severe infectious disease in poultry and selectively kills tumor cells, by inducing apoptosis and cytokines secretion. In this report, we study the mechanisms underlying NDV-induced apoptosis by investigating the unfolded protein response (UPR). We found that NDV infection activated all three branches of the UPR signaling (PERK-eIF2α, ATF6, and IRE1α) and triggered apoptosis, in avian cells (DF-1 and CEF) and in various human cancer cell types (HeLa, Cal27, HN13, A549, H1299, Huh7, and HepG2). Interestingly, the suppression of either apoptosis or UPR led to impaired NDV proliferation. Meanwhile, the inhibition of UPR by 4-PBA protected cells from NDV-induced apoptosis. Further study revealed that activation of PERK-eIF2α induced the expression of transcription factor CHOP, which subsequently promoted apoptosis by downregulating BCL-2/MCL-1, promoting JNK signaling and suppressing AKT signaling. In parallel, IRE1α mediated the splicing of XBP1 mRNA and resulted in the translation and nuclear translocation of XBP1s, thereby promoting the transcription of ER chaperones and components of ER-associated degradation (ERAD). Furthermore, IRE1α promoted apoptosis and cytokines secretion via the activation of JNK signaling. Knock down and overexpression studies showed that CHOP, IRE1α, XBP1, and JNK supported efficient virus proliferation. Our study demonstrates that the induction of eIF2α-CHOP-BCL-2/JNK and IRE1α-XBP1/JNK signaling cascades promote apoptosis and cytokines secretion, and these signaling cascades support NDV proliferation.",2019 Nov 26,"['Li, Yanrong', 'Jiang, Weiyu', 'Niu, Qiaona', 'Sun, Yingjie', 'Meng, Chunchun', 'Tan, Lei', 'Song, Cuiping', 'Qiu, Xusheng', 'Liao, Ying', 'Ding, Chan']",Cell Death Dis,,,True
e6846e658261dafd5aff4d0433bafa8118d6fa7d,PMC,Macrophage Coordination of the Interferon Lambda Immune Response,http://dx.doi.org/10.3389/fimmu.2019.02674,PMC6878940,31798594,CC BY,"Lambda interferons (IFN-λs) are a major component of the innate immune defense to viruses, bacteria, and fungi. In human liver, IFN-λ not only drives antiviral responses, but also promotes inflammation and fibrosis in viral and non-viral diseases. Here we demonstrate that macrophages are primary responders to IFN-λ, uniquely positioned to bridge the gap between IFN-λ producing cells and lymphocyte populations that are not intrinsically responsive to IFN-λ. While CD14(+) monocytes do not express the IFN-λ receptor, IFNLR1, sensitivity is quickly gained upon differentiation to macrophages in vitro. IFN-λ stimulates macrophage cytotoxicity and phagocytosis as well as the secretion of pro-inflammatory cytokines and interferon stimulated genes that mediate immune cell chemotaxis and effector functions. In particular, IFN-λ induced CCR5 and CXCR3 chemokines, stimulating T and NK cell migration, as well as subsequent NK cell cytotoxicity. Using immunofluorescence and cell sorting techniques, we confirmed that human liver macrophages expressing CD14 and CD68 are highly responsive to IFN-λ ex vivo. Together, these data highlight a novel role for macrophages in shaping IFN-λ dependent immune responses both directly through pro-inflammatory activity and indirectly by recruiting and activating IFN-λ unresponsive lymphocytes.",2019 Nov 19,"['Read, Scott A.', 'Wijaya, Ratna', 'Ramezani-Moghadam, Mehdi', 'Tay, Enoch', 'Schibeci, Steve', 'Liddle, Christopher', 'Lam, Vincent W. T.', 'Yuen, Lawrence', 'Douglas, Mark W.', 'Booth, David', 'George, Jacob', 'Ahlenstiel, Golo']",Front Immunol,,,True
572e7221874d7e5d1c4ed293e60f021ba1d59367,PMC,Tissue tropism and transmission ecology predict virulence of human RNA viruses,http://dx.doi.org/10.1371/journal.pbio.3000206,PMC6879112,31770368,CC BY,"Novel infectious diseases continue to emerge within human populations. Predictive studies have begun to identify pathogen traits associated with emergence. However, emerging pathogens vary widely in virulence, a key determinant of their ultimate risk to public health. Here, we use structured literature searches to review the virulence of each of the 214 known human-infective RNA virus species. We then use a machine learning framework to determine whether viral virulence can be predicted by ecological traits, including human-to-human transmissibility, transmission routes, tissue tropisms, and host range. Using severity of clinical disease as a measurement of virulence, we identified potential risk factors using predictive classification tree and random forest ensemble models. The random forest approach predicted literature-assigned disease severity of test data with mean accuracy of 89.4% compared to a null accuracy of 74.2%. In addition to viral taxonomy, the ability to cause systemic infection was the strongest predictor of severe disease. Further notable predictors of severe disease included having neural and/or renal tropism, direct contact or respiratory transmission, and limited (0 < R(0) ≤ 1) human-to-human transmissibility. We present a novel, to our knowledge, comparative perspective on the virulence of all currently known human RNA virus species. The risk factors identified may provide novel perspectives in understanding the evolution of virulence and elucidating molecular virulence mechanisms. These risk factors could also improve planning and preparedness in public health strategies as part of a predictive framework for novel human infections.",2019 Nov 26,"['Brierley, Liam', 'Pedersen, Amy B.', 'Woolhouse, Mark E. J.']",PLoS Biol,,,True
14ea8a52ed2b45376470ccf6f26da639daead456,PMC,Tissue tropism and transmission ecology predict virulence of human RNA viruses,http://dx.doi.org/10.1371/journal.pbio.3000206,PMC6879112,31770368,CC BY,"Novel infectious diseases continue to emerge within human populations. Predictive studies have begun to identify pathogen traits associated with emergence. However, emerging pathogens vary widely in virulence, a key determinant of their ultimate risk to public health. Here, we use structured literature searches to review the virulence of each of the 214 known human-infective RNA virus species. We then use a machine learning framework to determine whether viral virulence can be predicted by ecological traits, including human-to-human transmissibility, transmission routes, tissue tropisms, and host range. Using severity of clinical disease as a measurement of virulence, we identified potential risk factors using predictive classification tree and random forest ensemble models. The random forest approach predicted literature-assigned disease severity of test data with mean accuracy of 89.4% compared to a null accuracy of 74.2%. In addition to viral taxonomy, the ability to cause systemic infection was the strongest predictor of severe disease. Further notable predictors of severe disease included having neural and/or renal tropism, direct contact or respiratory transmission, and limited (0 < R(0) ≤ 1) human-to-human transmissibility. We present a novel, to our knowledge, comparative perspective on the virulence of all currently known human RNA virus species. The risk factors identified may provide novel perspectives in understanding the evolution of virulence and elucidating molecular virulence mechanisms. These risk factors could also improve planning and preparedness in public health strategies as part of a predictive framework for novel human infections.",2019 Nov 26,"['Brierley, Liam', 'Pedersen, Amy B.', 'Woolhouse, Mark E. J.']",PLoS Biol,,,False
64e6f7f7543033b48abf83a689cfaebec72626ab,PMC,Tissue tropism and transmission ecology predict virulence of human RNA viruses,http://dx.doi.org/10.1371/journal.pbio.3000206,PMC6879112,31770368,CC BY,"Novel infectious diseases continue to emerge within human populations. Predictive studies have begun to identify pathogen traits associated with emergence. However, emerging pathogens vary widely in virulence, a key determinant of their ultimate risk to public health. Here, we use structured literature searches to review the virulence of each of the 214 known human-infective RNA virus species. We then use a machine learning framework to determine whether viral virulence can be predicted by ecological traits, including human-to-human transmissibility, transmission routes, tissue tropisms, and host range. Using severity of clinical disease as a measurement of virulence, we identified potential risk factors using predictive classification tree and random forest ensemble models. The random forest approach predicted literature-assigned disease severity of test data with mean accuracy of 89.4% compared to a null accuracy of 74.2%. In addition to viral taxonomy, the ability to cause systemic infection was the strongest predictor of severe disease. Further notable predictors of severe disease included having neural and/or renal tropism, direct contact or respiratory transmission, and limited (0 < R(0) ≤ 1) human-to-human transmissibility. We present a novel, to our knowledge, comparative perspective on the virulence of all currently known human RNA virus species. The risk factors identified may provide novel perspectives in understanding the evolution of virulence and elucidating molecular virulence mechanisms. These risk factors could also improve planning and preparedness in public health strategies as part of a predictive framework for novel human infections.",2019 Nov 26,"['Brierley, Liam', 'Pedersen, Amy B.', 'Woolhouse, Mark E. J.']",PLoS Biol,,,False
7f62c112f606fca650a3a8390d4634b7545e0016,PMC,Tissue tropism and transmission ecology predict virulence of human RNA viruses,http://dx.doi.org/10.1371/journal.pbio.3000206,PMC6879112,31770368,CC BY,"Novel infectious diseases continue to emerge within human populations. Predictive studies have begun to identify pathogen traits associated with emergence. However, emerging pathogens vary widely in virulence, a key determinant of their ultimate risk to public health. Here, we use structured literature searches to review the virulence of each of the 214 known human-infective RNA virus species. We then use a machine learning framework to determine whether viral virulence can be predicted by ecological traits, including human-to-human transmissibility, transmission routes, tissue tropisms, and host range. Using severity of clinical disease as a measurement of virulence, we identified potential risk factors using predictive classification tree and random forest ensemble models. The random forest approach predicted literature-assigned disease severity of test data with mean accuracy of 89.4% compared to a null accuracy of 74.2%. In addition to viral taxonomy, the ability to cause systemic infection was the strongest predictor of severe disease. Further notable predictors of severe disease included having neural and/or renal tropism, direct contact or respiratory transmission, and limited (0 < R(0) ≤ 1) human-to-human transmissibility. We present a novel, to our knowledge, comparative perspective on the virulence of all currently known human RNA virus species. The risk factors identified may provide novel perspectives in understanding the evolution of virulence and elucidating molecular virulence mechanisms. These risk factors could also improve planning and preparedness in public health strategies as part of a predictive framework for novel human infections.",2019 Nov 26,"['Brierley, Liam', 'Pedersen, Amy B.', 'Woolhouse, Mark E. J.']",PLoS Biol,,,False
338d5cc4af296ec1ecd8ed7c63f6ac522ff583db,PMC,The in vivo ISGylome links ISG15 to metabolic pathways and autophagy upon Listeria monocytogenes infection,http://dx.doi.org/10.1038/s41467-019-13393-x,PMC6879477,31772204,CC BY,"ISG15 is an interferon-stimulated, ubiquitin-like protein, with anti-viral and anti-bacterial activity. Here, we map the endogenous in vivo ISGylome in the liver following Listeria monocytogenes infection by combining murine models of reduced or enhanced ISGylation with quantitative proteomics. Our method identifies 930 ISG15 sites in 434 proteins and also detects changes in the host ubiquitylome. The ISGylated targets are enriched in proteins which alter cellular metabolic processes, including upstream modulators of the catabolic and antibacterial pathway of autophagy. Computational analysis of substrate structures reveals that a number of ISG15 modifications occur at catalytic sites or dimerization interfaces of enzymes. Finally, we demonstrate that animals and cells with enhanced ISGylation have increased basal and infection-induced autophagy through the modification of mTOR, WIPI2, AMBRA1, and RAB7. Taken together, these findings ascribe a role of ISGylation to temporally reprogram organismal metabolism following infection through direct modification of a subset of enzymes in the liver.",2019 Nov 26,"['Zhang, Yifeng', 'Thery, Fabien', 'Wu, Nicholas C.', 'Luhmann, Emma K.', 'Dussurget, Olivier', 'Foecke, Mariko', 'Bredow, Clara', 'Jiménez-Fernández, Daniel', 'Leandro, Kevin', 'Beling, Antje', 'Knobeloch, Klaus-Peter', 'Impens, Francis', 'Cossart, Pascale', 'Radoshevich, Lilliana']",Nat Commun,,,True
bae10a20bc6c70403e8f6ab4dbe4b8f56db964d3,PMC,The in vivo ISGylome links ISG15 to metabolic pathways and autophagy upon Listeria monocytogenes infection,http://dx.doi.org/10.1038/s41467-019-13393-x,PMC6879477,31772204,CC BY,"ISG15 is an interferon-stimulated, ubiquitin-like protein, with anti-viral and anti-bacterial activity. Here, we map the endogenous in vivo ISGylome in the liver following Listeria monocytogenes infection by combining murine models of reduced or enhanced ISGylation with quantitative proteomics. Our method identifies 930 ISG15 sites in 434 proteins and also detects changes in the host ubiquitylome. The ISGylated targets are enriched in proteins which alter cellular metabolic processes, including upstream modulators of the catabolic and antibacterial pathway of autophagy. Computational analysis of substrate structures reveals that a number of ISG15 modifications occur at catalytic sites or dimerization interfaces of enzymes. Finally, we demonstrate that animals and cells with enhanced ISGylation have increased basal and infection-induced autophagy through the modification of mTOR, WIPI2, AMBRA1, and RAB7. Taken together, these findings ascribe a role of ISGylation to temporally reprogram organismal metabolism following infection through direct modification of a subset of enzymes in the liver.",2019 Nov 26,"['Zhang, Yifeng', 'Thery, Fabien', 'Wu, Nicholas C.', 'Luhmann, Emma K.', 'Dussurget, Olivier', 'Foecke, Mariko', 'Bredow, Clara', 'Jiménez-Fernández, Daniel', 'Leandro, Kevin', 'Beling, Antje', 'Knobeloch, Klaus-Peter', 'Impens, Francis', 'Cossart, Pascale', 'Radoshevich, Lilliana']",Nat Commun,,,False
3ff80f738629339b9e16ebe2a12a10dcbf325aa0,PMC,The in vivo ISGylome links ISG15 to metabolic pathways and autophagy upon Listeria monocytogenes infection,http://dx.doi.org/10.1038/s41467-019-13393-x,PMC6879477,31772204,CC BY,"ISG15 is an interferon-stimulated, ubiquitin-like protein, with anti-viral and anti-bacterial activity. Here, we map the endogenous in vivo ISGylome in the liver following Listeria monocytogenes infection by combining murine models of reduced or enhanced ISGylation with quantitative proteomics. Our method identifies 930 ISG15 sites in 434 proteins and also detects changes in the host ubiquitylome. The ISGylated targets are enriched in proteins which alter cellular metabolic processes, including upstream modulators of the catabolic and antibacterial pathway of autophagy. Computational analysis of substrate structures reveals that a number of ISG15 modifications occur at catalytic sites or dimerization interfaces of enzymes. Finally, we demonstrate that animals and cells with enhanced ISGylation have increased basal and infection-induced autophagy through the modification of mTOR, WIPI2, AMBRA1, and RAB7. Taken together, these findings ascribe a role of ISGylation to temporally reprogram organismal metabolism following infection through direct modification of a subset of enzymes in the liver.",2019 Nov 26,"['Zhang, Yifeng', 'Thery, Fabien', 'Wu, Nicholas C.', 'Luhmann, Emma K.', 'Dussurget, Olivier', 'Foecke, Mariko', 'Bredow, Clara', 'Jiménez-Fernández, Daniel', 'Leandro, Kevin', 'Beling, Antje', 'Knobeloch, Klaus-Peter', 'Impens, Francis', 'Cossart, Pascale', 'Radoshevich, Lilliana']",Nat Commun,,,True
5d36857d0cdaff4320e21e718bdc2e12599ef124,PMC,Development and comparison of enzyme-linked immunosorbent assays based on recombinant trimeric full-length and truncated spike proteins for detecting antibodies against porcine epidemic diarrhea virus,http://dx.doi.org/10.1186/s12917-019-2171-7,PMC6880432,31775769,CC BY,"BACKGROUND: Since 2010, outbreaks of genotype 2 (G2) porcine epidemic diarrhea virus (PEDV) have caused high mortality in neonatal piglets and have had devastating impacts on the swine industry in many countries. A reliable serological assay for evaluating the PEDV-specific humoral and mucosal immune response is important for disease survey, monitoring the efficacy of immunization, and designing strategies for the prevention and control of PED. Two PEDV spike (S) glycoprotein-based indirect enzyme-linked immunosorbent assays (ELISAs) were developed using G2b PEDV-Pintung 52 (PEDV-PT) trimeric full-length S and truncated S(1–501) proteins derived from the human embryonic kidney (HEK)-293 cell expression system. The truncated S(1–501) protein was selected from a superior expressed stable cell line. The sensitivity and specificity of these two ELISAs were compared to immunostaining of G2b PEDV-PT infected cells and to a commercial nucleocapsid (N)-based indirect ELISA kit using a panel of PEDV negative and hyperimmune sera. RESULTS: The commercial N-based ELISA exhibited a sensitivity of 37%, a specificity of 100%, and a fair agreement (kappa = 0.37) with the immunostaining result. In comparison, the full-length S-based ELISA showed a sensitivity of 97.8%, a specificity of 94%, and an almost perfect agreement (kappa = 0.90) with the immunostaining result. Interestingly, the S(1–501)-based ELISA had even higher sensitivity of 98.9% and specificity of 99.1%, and an almost perfect agreement (kappa = 0.97) with the immunostaining result. A fair agreement (kappa< 0.4) was seen between the commercial N-based ELISA and either of our S-based ELISAs. However, the results of the full-length S-based ELISA shared an almost perfect agreement (kappa = 0.92) with that of S(1–501)-based ELISA. CONCLUSIONS: Both full-length S-based and S(1–501)-based ELISAs exhibit high sensitivity and high specificity for detecting antibodies against PEDVs. Considering the high protein yield and cost-effectiveness, the S(1–501)-based ELISA could be used as a reliable, sensitive, specific, and economic serological test for PEDV.",2019 Nov 27,"['Chang, Chia-Yu', 'Peng, Ju-Yi', 'Cheng, Yun-Han', 'Chang, Yen-Chen', 'Wu, Yen-Tse', 'Tsai, Pei-Shiue', 'Chiou, Hue-Ying', 'Jeng, Chian-Ren', 'Chang, Hui-Wen']",BMC Vet Res,,,True
c6ee9f876eedfbe7aa60473dcad1e8fcdc4c3a2d,PMC,Molecular Detection and Genetic Characterization of Novel RNA Viruses in Wild and Synanthropic Rodents and Shrews in Kenya,http://dx.doi.org/10.3389/fmicb.2019.02696,PMC6881279,31824465,CC BY,"The majority of emerging and reemerging zoonotic viral pathogens are RNA viruses. Pathogen discovery programs of emerging infectious diseases (EIDs) in wildlife have implicated rodents and shrews as hosts of diverse human pathogens, such as hantaviruses, arenaviruses, paramyxoviruses, etc. Despite these threats, little is known about the diversity of viruses circulating among rodents and shrews in Kenya, meaning the risk of infectious disease outbreak from these small mammals could be oblivious. This study reports the first surveillance toward understanding the diversity of RNA viruses carried by rodents and shrews in areas of high-potential contact with humans in Kenya through molecular detection. A total of 617 samples comprising fecal, urine, and tissues from 138 rodents and 5 shrews were screened for eight different families of viruses using RT-PCR assays. The results highlight the presence of diverse astroviruses, paramyxoviruses, hepeviruses, and arenavirus, circulating in both wild and synanthropic Kenyan rodents and shrews. Most of the viruses detected in this study are novel strains and some belong to the families that contain important human viral pathogens. Notably, a novel arenavirus was detected in Grammomys macmillani, a rodent species newly identified to harbor arenavirus, and it potentially represent a novel arenavirus species. Our findings demonstrate the need for continued pathogen surveillance among these small mammals as well as among the vulnerable and exposed livestock and humans. This would help in development and implementation of effective preventive and control strategies on EIDs in countries with rich wildlife biodiversity like Kenya.",2019 Nov 21,"['Onyuok, Samson Omondi', 'Hu, Ben', 'Li, Bei', 'Fan, Yi', 'Kering, Kelvin', 'Ochola, Griphin Ochieng', 'Zheng, Xiao-Shuang', 'Obanda, Vincent', 'Ommeh, Sheila', 'Yang, Xing-Lou', 'Agwanda, Bernard', 'Shi, Zheng-Li']",Front Microbiol,,,True
54c8da2f34d0e830818e213cfa74e105e10dac38,PMC,The dynamics and interactions of respiratory pathogen carriage among French pilgrims during the 2018 Hajj,http://dx.doi.org/10.1080/22221751.2019.1693247,PMC6882464,31749410,CC BY,"We conducted this study to describe the dynamics of the acquisition of respiratory pathogens, their potential interactions and risk factors for possible lower respiratory tract infection symptoms (LRTI) among French pilgrims during the 2018 Hajj. Each participant underwent four successive systematic nasopharyngeal swabs before and during their stay in Saudi Arabia. Carriage of the main respiratory pathogens was assessed by PCR. 121 pilgrims were included and 93.4% reported respiratory symptoms during the study period. The acquisition of rhinovirus, coronaviruses and Staphylococcus aureus occurred soon after arrival in Saudi Arabia and rates decreased gradually after days 5 and 6. In contrast, Streptococcus pneumoniae and Klebsiella pneumoniae carriage increased progressively until the end of the stay in Saudi Arabia. Haemophilus influenzae and Moraxella catarrhalis carriage increased starting around days 12 and 13, following an initial clearance. Influenza viruses were rarely isolated. We observed an independent positive mutual association between S. aureus and rhinovirus carriage and between H. influenzae and M. catarrhalis carriage. Dual carriage of H. influenzae and M. catarrhalis was strongly associated with S. pneumoniae carriage (OR = 6.22). Finally, our model showed that M. catarrhalis carriage was negatively associated with K. pneumoniae carriage. Chronic respiratory disease was associated with symptoms of LRTI. K. pneumoniae, M. catarrhalis-S. aureus and H. influenzae-rhinovirus dual carriage was associated with LRTI symptoms. Our data suggest that RTIs at the Hajj are a result of complex interactions between a number of respiratory viruses and bacteria.",2019 Nov 21,"['Hoang, Van-Thuan', 'Dao, Thi-Loi', 'Ly, Tran Duc Anh', 'Belhouchat, Khadidja', 'Chaht, Kamel Larbi', 'Gaudart, Jean', 'Mrenda, Bakridine Mmadi', 'Drali, Tassadit', 'Yezli, Saber', 'Alotaibi, Badriah', 'Fournier, Pierre-Edouard', 'Raoult, Didier', 'Parola, Philippe', 'de Santi, Vincent Pommier', 'Gautret, Philippe']",Emerg Microbes Infect,,,True
48370f9638e4b2f33483c33a50168c18009cd9b4,PMC,A real-time spatio-temporal syndromic surveillance system with application to small companion animals,http://dx.doi.org/10.1038/s41598-019-53352-6,PMC6882870,31780686,CC BY,"Lack of disease surveillance in small companion animals worldwide has contributed to a deficit in our ability to detect and respond to outbreaks. In this paper we describe the first real-time syndromic surveillance system that conducts integrated spatio-temporal analysis of data from a national network of veterinary premises for the early detection of disease outbreaks in small animals. We illustrate the system’s performance using data relating to gastrointestinal disease in dogs and cats. The data consist of approximately one million electronic health records for dogs and cats, collected from 458 UK veterinary premises between March 2014 and 2016. For this illustration, the system predicts the relative reporting rate of gastrointestinal disease amongst all presentations, and updates its predictions as new data accrue. The system was able to detect simulated outbreaks of varying spatial geometry, extent and severity. The system is flexible: it generates outcomes that are easily interpretable; the user can set their own outbreak detection thresholds. The system provides the foundation for prompt detection and control of health threats in companion animals.",2019 Nov 28,"['Hale, Alison C.', 'Sánchez-Vizcaíno, Fernando', 'Rowlingson, Barry', 'Radford, Alan D.', 'Giorgi, Emanuele', 'O’Brien, Sarah J.', 'Diggle, Peter J.']",Sci Rep,,,False
491b2bd6232dd000fc79008d3d7044c2a1fece64,PMC,A real-time spatio-temporal syndromic surveillance system with application to small companion animals,http://dx.doi.org/10.1038/s41598-019-53352-6,PMC6882870,31780686,CC BY,"Lack of disease surveillance in small companion animals worldwide has contributed to a deficit in our ability to detect and respond to outbreaks. In this paper we describe the first real-time syndromic surveillance system that conducts integrated spatio-temporal analysis of data from a national network of veterinary premises for the early detection of disease outbreaks in small animals. We illustrate the system’s performance using data relating to gastrointestinal disease in dogs and cats. The data consist of approximately one million electronic health records for dogs and cats, collected from 458 UK veterinary premises between March 2014 and 2016. For this illustration, the system predicts the relative reporting rate of gastrointestinal disease amongst all presentations, and updates its predictions as new data accrue. The system was able to detect simulated outbreaks of varying spatial geometry, extent and severity. The system is flexible: it generates outcomes that are easily interpretable; the user can set their own outbreak detection thresholds. The system provides the foundation for prompt detection and control of health threats in companion animals.",2019 Nov 28,"['Hale, Alison C.', 'Sánchez-Vizcaíno, Fernando', 'Rowlingson, Barry', 'Radford, Alan D.', 'Giorgi, Emanuele', 'O’Brien, Sarah J.', 'Diggle, Peter J.']",Sci Rep,,,True
7bc864bf9c487c23ecb9213cffedfa9590e6d56a,PMC,Causes and countermeasures for repeated outbreaks of hepatitis A among adults in Korea,http://dx.doi.org/10.4178/epih.e2019038,PMC6883026,31715685,CC BY,"The 2019 hepatitis A outbreak has become increasingly prevalent among adults in Korea and is the largest outbreak since that in 2009-2010. The incidence in the current outbreak is highest among adults aged 35-44 years, corresponding to the peak incidence among those aged 25-34 years 10 years ago. This may indicate a cohort effect in the corresponding age group. Causes of these repeated outbreaks of hepatitis A in Korea are low level of immunity among adults, Korean food culture that consumes raw seafood such as salted clam and inadequate public health system. Among countermeasures, along with general infectious disease control measures including control of the infectious agent, infection spread, and host, urgent actions are needed to review the vaccination policy and establish an adequate public health system.",2019 Sep 22,"['Ki, Moran', 'Son, Hyunjin', 'Choi, Bo Youl']",Epidemiol Health,,,True
56119c20c98afd894ba2a4433ad9636ed60ce2ee,PMC,Causes and countermeasures for repeated outbreaks of hepatitis A among adults in Korea,http://dx.doi.org/10.4178/epih.e2019038,PMC6883026,31715685,CC BY,"The 2019 hepatitis A outbreak has become increasingly prevalent among adults in Korea and is the largest outbreak since that in 2009-2010. The incidence in the current outbreak is highest among adults aged 35-44 years, corresponding to the peak incidence among those aged 25-34 years 10 years ago. This may indicate a cohort effect in the corresponding age group. Causes of these repeated outbreaks of hepatitis A in Korea are low level of immunity among adults, Korean food culture that consumes raw seafood such as salted clam and inadequate public health system. Among countermeasures, along with general infectious disease control measures including control of the infectious agent, infection spread, and host, urgent actions are needed to review the vaccination policy and establish an adequate public health system.",2019 Sep 22,"['Ki, Moran', 'Son, Hyunjin', 'Choi, Bo Youl']",Epidemiol Health,,,False
6c38d70883a1c03b826da59f7169e63ac854a86e,PMC,Causes and countermeasures for repeated outbreaks of hepatitis A among adults in Korea,http://dx.doi.org/10.4178/epih.e2019038,PMC6883026,31715685,CC BY,"The 2019 hepatitis A outbreak has become increasingly prevalent among adults in Korea and is the largest outbreak since that in 2009-2010. The incidence in the current outbreak is highest among adults aged 35-44 years, corresponding to the peak incidence among those aged 25-34 years 10 years ago. This may indicate a cohort effect in the corresponding age group. Causes of these repeated outbreaks of hepatitis A in Korea are low level of immunity among adults, Korean food culture that consumes raw seafood such as salted clam and inadequate public health system. Among countermeasures, along with general infectious disease control measures including control of the infectious agent, infection spread, and host, urgent actions are needed to review the vaccination policy and establish an adequate public health system.",2019 Sep 22,"['Ki, Moran', 'Son, Hyunjin', 'Choi, Bo Youl']",Epidemiol Health,,,False
8142d13b88328405d5302f1e899e5c2a8c1df196,PMC,Roles of aminoacyl-tRNA synthetases in immune regulation and immune diseases,http://dx.doi.org/10.1038/s41419-019-2145-5,PMC6883034,31780718,CC BY,"Aminoacyl-tRNA synthetases (ARSs) play a vital role in protein synthesis by linking amino acids to their cognate transfer RNAs (tRNAs). This typical function has been well recognized over the past few decades. However, accumulating evidence reveals that ARSs are involved in a wide range of physiological and pathological processes apart from translation. Strikingly, certain ARSs are closely related to different types of immune responses. In this review, we address the infection and immune responses induced by pathogen ARSs, as well as the potential anti-infective compounds that target pathogen ARSs. Meanwhile, we describe the functional mechanisms of ARSs in the development of immune cells. In addition, we focus on the roles of ARSs in certain immune diseases, such as autoimmune diseases, infectious diseases, and tumor immunity. Although our knowledge of ARSs in the immunological context is still in its infancy, research in this field may provide new ideas for the treatment of immune-related diseases.",2019 Nov 28,"['Nie, Anzheng', 'Sun, Bao', 'Fu, Zhihui', 'Yu, Dongsheng']",Cell Death Dis,,,True
892e0a43f862ce5adb7611e7f5243e2a30724800,PMC,Respiratory tract infections among French Hajj pilgrims from 2014 to 2017,http://dx.doi.org/10.1038/s41598-019-54370-0,PMC6883043,31780750,CC BY,"Respiratory tract infections (RTIs) are common among Hajj pilgrims, but risk factors for RTIs and respiratory pathogen acquisition during the Hajj are not clearly identified. Based on previous studies, most frequent pathogens acquired by Hajj pilgrims were investigated: rhinovirus, human coronaviruses, influenza viruses, Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae and Haemophilus influenzae. 485 pilgrims were included. 82.1% presented with RTIs. Respiratory chronic diseases were associated with cough, Influenza-like illness (ILI) and the acquisition of H. influenzae. Vaccination against invasive pneumococcal diseases (IPD) and influenza was associated with a decrease in the acquisition of S. pneumoniae and prevalence of ILI (aRR = 0.53, 95%CI [0.39–0.73] and aRR = 0.69, 95%CI [0.52–0.92] respectively). Individuals carrying rhinovirus and H. influenzae-S. pneumoniae together were respectively twice and five times more likely to have respiratory symptoms. Individual with H. influenzae-K. pneumoniae carriage were twice (p = 0.04) as likely to develop a cough. The use of disposable handkerchiefs was associated with a decrease in the acquisition of S. aureus (aRR = 0.75, 95%CI [0.57–0.97]). Results could be used to identify pilgrims at increased risk of RTIs and acquisition of respiratory pathogens. Results also confirm the effectiveness of influenza and IPD vaccinations in reducing ILI symptoms and acquisition of S. pneumoniae carriage respectively.",2019 Nov 28,"['Hoang, Van-Thuan', 'Ali-Salem, Saliha', 'Belhouchat, Khadidja', 'Meftah, Mohammed', 'Sow, Doudou', 'Dao, Thi-Loi', 'Ly, Tran Duc Anh', 'Drali, Tassadit', 'Ninove, Laetitia', 'Yezli, Saber', 'Alotaibi, Badriah', 'Raoult, Didier', 'Parola, Philippe', 'Pommier de Santi, Vincent', 'Gautret, Philippe']",Sci Rep,,,True
6e7a017e7e61ae4634cd4be5ad5646470e43054d,PMC,Posters Have Limited Utility in Conveying a Message of Antimicrobial Stewardship to Pet Owners,http://dx.doi.org/10.3389/fvets.2019.00421,PMC6883349,31824973,CC BY,"Pet owners frequently administer antimicrobials to their pets and therefore have an important role to play in promoting antimicrobial stewardship in veterinary medicine. However, best methods of educating pet owners about antimicrobial stewardship have yet to be defined. While visual materials such as brochures and posters are often used in health promotion campaigns, their effectiveness in veterinary medicine is unknown. The objective of this study was to determine whether pet owners noticed and retained the message of a poster with an antimicrobial stewardship message placed in veterinary clinic exam rooms. A total of 111 pet owners from five veterinary clinics (three general practices, two low-cost clinics) in the greater Philadelphia area participated in the study. Participants completed a survey asking whether they noticed the poster and if they could paraphrase its message. In a follow-up survey, an antibiotic knowledge score was calculated from answers to questions assessing their knowledge of the poster message. Baseline knowledge was assessed by asking participants to define antibiotic resistance. At the end of the study, veterinarians at participating clinics were interviewed about their experiences with the poster. Only 51 (46.4%) participants noticed the poster, and only 11 (9.9%) could partially or completely reproduce its message. No demographic or clinic-level factors were significantly associated with noticing the poster or recalling its message. Antibiotic knowledge scores were highly correlated (ρ = 0.87, p < 0.001) with baseline knowledge and not affected by viewing the poster (p = 0.955). Veterinarians expressed skepticism that the poster was effective in conveying a message of judicious antibiotic use to clients and noted no difference in the frequency with which they discussed antibiotic resistance or felt pressured to prescribe antibiotics by their clients. Posters alone will likely have limited impact in conveying a message of judicious antibiotic use to pet owners. However, they might be useful as part of an active, multi-modal education strategy, especially if complemented by veterinarian actions.",2019 Nov 22,"['Redding, Laurel E.', 'Cole, Stephen D.']",Front Vet Sci,,,True
a56b804d0fb9dfe5c6e194c8a4e5b68d0c040adb,PMC,The Usefulness of Lung Ultrasound for the Aetiological Diagnosis of Community-Acquired Pneumonia in Children,http://dx.doi.org/10.1038/s41598-019-54499-y,PMC6884636,31784642,CC BY,"The aetiology of community-acquired pneumonia (CAP) is not easy to establish. As lung ultrasound (LUS) has already proved to be an excellent diagnostic tool for CAP, we analysed its usefulness for discriminating between the aetiologically different types of CAP in children. We included 147 children hospitalized because of CAP. LUS was performed in all patients at admission, and follow-up LUS was performed in most patients. LUS-detected consolidations in viral CAP were significantly smaller, with a median diameter of 15 mm, compared to 20 mm in atypical bacterial CAP (p = 0.05) and 30 mm in bacterial CAP (p < 0.001). Multiple consolidations were detected in 65.4% of patients with viral CAP and in 17.3% of patients with bacterial CAP (p < 0.001). Bilateral consolidations were also more common in viral CAP than in bacterial CAP (51.9% vs. 8.0%, p < 0.001). At follow-up, a regression of consolidations was observed in 96.6% of patients with bacterial CAP and in 33.3% of patients with viral CAP (p < 0.001). We found LUS to be especially suitable for differentiating bacterial CAP from CAP due to other aetiologies. However, LUS must be interpreted in light of clinical and laboratory findings.",2019 Nov 29,"['Berce, Vojko', 'Tomazin, Maja', 'Gorenjak, Mario', 'Berce, Tadej', 'Lovrenčič, Barbara']",Sci Rep,,,True
097b9b4ada3e89942ea196c59226e95da1b7969f,PMC,Oral vitamin A supplementation of porcine epidemic diarrhea virus infected gilts enhances IgA and lactogenic immune protection of nursing piglets,http://dx.doi.org/10.1186/s13567-019-0719-y,PMC6884901,31783923,CC BY,"Vitamin A (VA) has pleiotropic effects on the immune system and is critical for mucosal immune function and intestinal lymphocyte trafficking. We hypothesized that oral VA supplementation of porcine epidemic diarrhea virus (PEDV)-infected pregnant gilts would enhance the gut-mammary gland-secretory IgA axis to boost lactogenic immunity and passive protection of nursing piglets against PEDV challenge. Gilts received daily oral retinyl acetate (30 000 IU) starting at gestation day 76 throughout lactation. At 3–4 weeks pre-partum, VA-supplemented (PEDV + VA) and non-supplemented (PEDV) gilts were PEDV or mock inoculated (mock + VA and mock, respectively). PEDV + VA gilts had decreased mean PEDV RNA shedding titers and diarrhea scores. To determine if lactogenic immunity correlated with protection, all piglets were PEDV-challenged at 3–5 days post-partum. The survival rate of PEDV + VA litters was 74.2% compared with 55.9% in PEDV litters. Mock and mock + VA litter survival rates were 5.7% and 8.3%, respectively. PEDV + VA gilts had increased PEDV IgA antibody secreting cells and PEDV IgA antibodies in serum pre-partum and IgA(+)β7(+) (gut homing) cells in milk post piglet challenge compared with PEDV gilts. Our findings suggest that oral VA supplementation may act as an adjuvant during pregnancy, enhancing maternal IgA and lactogenic immune protection in nursing piglets.",2019 Nov 29,"['Langel, Stephanie N.', 'Paim, Francine Chimelo', 'Alhamo, Moyasar A.', 'Lager, Kelly M.', 'Vlasova, Anastasia N.', 'Saif, Linda J.']",Vet Res,,,True
69735aa238c755d99f12f259ae3d7ac5a6210978,PMC,Rhinovirus species and tonsillar immune responses,http://dx.doi.org/10.1186/s13601-019-0302-7,PMC6886181,31827765,CC BY,"BACKGROUND: Rhinovirus A and C infections are important contributors to asthma induction and exacerbations. No data exist on the interaction of local immune responses in rhinovirus infection. Therefore, we aimed to determine the tonsillar immune responses according to rhinovirus A, B and C infections. METHODS: We collected tonsillar samples, nasopharyngeal aspirates and peripheral blood from 42 rhinovirus positive tonsillectomy patients. Fifteen respiratory viruses or their types were investigated from nasopharynx and tonsil tissue, and rhinovirus species were typed. The expression of 10 cytokines and 4 transcription factors (IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2 and Tbet) were studied from tonsil tissue by quantitative PCR. A standard questionnaire of respiratory symptoms and health was filled by the patient or his/her guardian. The patients were divided into three groups by the determination of rhinovirus species. RESULTS: Overall, 16 patients had rhinovirus A, 12 rhinovirus B and 14 rhinovirus C infection. In rhinovirus B positive group there were significantly less men (P = 0.0072), less operated in spring (P = 0.0096) and more operated in fall (P = 0.030) than in rhinovirus A or C groups. Rhinovirus A positive patients had more respiratory symptoms (P = 0.0074) and particularly rhinitis (P = 0.036) on the operation day. There were no significant differences between the groups in virus codetection. In adjusted analysis, rhinovirus C infections were associated with increased IFN-α (P = 0.045) and decreased RORC2 expression (P = 0.025). CONCLUSIONS: Rhinovirus species associated differently with clinical characteristics and tonsillar cytokine responses.",2019 Dec 2,"['Mikola, Emilia', 'Palomares, Oscar', 'Turunen, Riitta', 'Waris, Matti', 'Ivaska, Lotta E.', 'Silvoniemi, Antti', 'Puhakka, Tuomo', 'Rückert, Beate', 'Vuorinen, Tytti', 'Akdis, Mübeccel', 'Akdis, Cezmi A.', 'Jartti, Tuomas']",Clin Transl Allergy,,,True
ae94601843c7f14fc95e723c9bce16232b0bfd70,PMC,Insulin-Like Growth Factor 1 Regulates Acute Inflammatory Lung Injury Mediated by Influenza Virus Infection,http://dx.doi.org/10.3389/fmicb.2019.02541,PMC6887893,31849847,CC BY,"The acute inflammatory lung injury is an important cause of death due to influenza A virus (IAV) infection. Insulin-like growth factor 1 (IGF1) played an important role in the regulation of inflammation in the immune system. To investigate the role of IGF1 in IAV-mediated acute inflammatory lung injury, the expression of IGF1 and inflammatory cytokines was tested after IAV A/Puerto Rico/8/1934 (H1N1; abbreviated as PR8) infection in A549 cells. Then, a BALB/c mouse model of PR8 infection was established. On days 3, 5, 7, and 9 post-infection, the mice lung tissue was collected to detect the expression changes in IGF1 mRNA and protein. The mice were divided into four groups: (1) PBS (abbreviation of phosphate buffered saline); (2) PR8 + PBS; (3) PR8 + IGF1; and (4) PR8 + PPP (abbreviation of picropodophyllin, the IGF1 receptor inhibitor). The body weight and survival rate of the mice were monitored daily, and the clinical symptoms of the mice were recorded. On day 5 post-infection, the mice were sacrificed to obtain the serum and lung tissues. The expression of inflammatory cytokines in the serum was detected by enzyme linked immunosorbent assay; lung injury was observed by hematoxylin-eosin staining; the viral proliferation in the lung was detected by real-time quantitative PCR; and the protein expression of the main molecules in the phosphatidylinositol-3-kinases/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling pathways was detected by Western blot. It was found that IGF1 expression is upregulated in A549 cells and BALB/c mice infected with PR8, whereas IGF1 regulated the expression of inflammatory cytokines induced by PR8 infection. Overexpression of IGF1 aggravated the IAV-mediated inflammatory response, whereas the inhibition of IGF1 receptor reduced such inflammatory response. The phosphorylation of IGF1 receptor triggered the PI3K/AKT and MAPK signaling pathways to induce an inflammatory response after IAV infection. Therefore, IGF1 plays an important immune function in IAV-mediated acute inflammatory lung injury. IGF1 may provide a therapeutic target for humans in response to an influenza outbreak, and inhibition of IGF1 or IGF1 receptor may represent a novel approach to influenza treatment.",2019 Nov 26,"['Li, Guiping', 'Zhou, Lijuan', 'Zhang, Can', 'Shi, Yun', 'Dong, Derong', 'Bai, Miao', 'Wang, Rong', 'Zhang, Chuanfu']",Front Microbiol,,,True
4716aa61386cb52b7aa834b557cb4e2ac7ec4cad,PMC,The Role of the Lung’s Microbiome in the Pathogenesis and Progression of Idiopathic Pulmonary Fibrosis,http://dx.doi.org/10.3390/ijms20225618,PMC6888416,31717661,CC BY,"Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease that commonly affects older adults and is associated with the histopathological and/or radiological patterns of usual interstitial pneumonia (UIP). Despite significant advances in our understanding of disease pathobiology and natural history, what causes IPF remains unknown. A potential role for infection in the disease’s pathogenesis and progression or as a trigger of acute exacerbation has long been postulated, but initial studies based on traditional culture methods have yielded inconsistent results. The recent application to IPF of culture-independent techniques for microbiological analysis has revealed previously unappreciated alterations of the lung microbiome, as well as an increased bacterial burden in the bronchoalveolar lavage (BAL) of IPF patients, although correlation does not necessarily entail causation. In addition, the lung microbiome remains only partially characterized and further research should investigate organisms other than bacteria and viruses, including fungi. The clarification of the role of the microbiome in the pathogenesis and progression of IPF may potentially allow its manipulation, providing an opportunity for targeted therapeutic intervention.",2019 Nov 10,"['Spagnolo, Paolo', 'Molyneaux, Philip L.', 'Bernardinello, Nicol', 'Cocconcelli, Elisabetta', 'Biondini, Davide', 'Fracasso, Federico', 'Tiné, Mariaenrica', 'Saetta, Marina', 'Maher, Toby M.', 'Balestro, Elisabetta']",Int J Mol Sci,,,True
dfbb7bb506552b06794dbcefe56911e2a91a908b,PMC,"Assessment of Knowledge, Attitude and Practice towards Prevention of Respiratory Tract Infections among Hajj and Umrah Pilgrims from Malaysia in 2018",http://dx.doi.org/10.3390/ijerph16224569,PMC6888533,31752224,CC BY,"Respiratory tract infection (RTI) is a major public health challenge during the Muslim pilgrimage to Makkah. This study aims to evaluate the knowledge, attitude, and practice of Malaysian Hajj and Umrah pilgrims towards the prevention of RTIs in 2018 and determine correlations among three domains. A cross-sectional study was conducted among 225 Umrah and Hajj pilgrims. Knowledge, attitude, and practice (KAP) towards RTI prevention was assessed by using a validated self-administered questionnaire among pilgrims attending a weekly orientation course organized by private Hajj/Umrah companies. Out of 225 participants, 65.9% of respondents were female with the mean (SD) age of 46.74 (13.38) years. The interquartile range (IQR) score for knowledge is 18.0 (6.0), the mean scores of attitude and practice are 32.65 (4.72) and 25.30 (4.9). respectively. Significant and negative linear correlations between knowledge and practice (r = −0.232, p < 0.001), and attitude and practice (r = 0.134, p = 0.045) were observed. Results from the current study showed good knowledge of RTIs among Malaysian pilgrims. However, a poor attitude was reflected in their preventive practice behaviors. This will further help in the prevention and management of RTIs during Hajj and Umrah. Therefore, an extensive educational health campaign should be provided to pilgrims to create awareness.",2019 Nov 18,"['Dauda Goni, Mohammed', 'Hasan, Habsah', 'Naing, Nyi Nyi', 'Wan-Arfah, Nadiah', 'Zeiny Deris, Zakuan', 'Nor Arifin, Wan', 'Abubakar Baaba, Aisha']",Int J Environ Res Public Health,,,True
4e30ead25a8574d9013af8ea6f6d5a1be19e41b1,PMC,"Low to medium-low risk perception for dengue, chikungunya and Zika outbreaks by infectious diseases physicians in France, Western Europe",http://dx.doi.org/10.1186/s12889-019-7317-9,PMC6889449,31366341,CC BY,"BACKGROUND: Many tropical countries are currently experiencing dengue (DEN), chikungunya (CHIK) and also more recently Zika (ZIKA) epidemics (particularly in Latin America). Although the risk of transmission and spread of these infections in temperate regions remains a controversial issue, vector-borne diseases have been widely reported in the media and have been the focus of preventive strategies by national and international policy-makers and public health authorities. In this context, we wanted to determine the extent of risk perception in infectious diseases (ID) physicians of the current and future risk of arboviral disease introduction, autochthonous case development and epidemic scenarios in France, Western Europe. METHODS: To this aim, we developed an original standardized questionnaire survey which was disseminated by the French Infectious Diseases Society to ID physician members. RESULTS: We found that ID physicians perceived the risk of introduction and outbreak development of DEN, CHIK and ZIKA in France to be low to medium-low. Generalized Linear Model(s) identified medical school training, the extent of professional experience, and awareness of the French national plan regarding arboviral infections as significant predictors for lower risk perception among respondents. CONCLUSION: Despite the fact that arboviral diseases are increasingly being imported into France, sometimes resulting in sporadic autochtonous transmission, French ID physicians do not perceive the risk as high. Better communication and education targeting health professionals and citizens will be needed to enhance the effectiveness of the French national plan to prepare against arboviral diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-019-7317-9) contains supplementary material, which is available to authorized users.",2019 Jul 31,"['Le Tyrant, Marion', 'Bley, Daniel', 'Leport, Catherine', 'Alfandari, Serge', 'Guégan, Jean-François']",BMC Public Health,,,True
23d0641f1f78528bbf3fa7b0b749abc1299a9cb4,PMC,Local risk perception enhances epidemic control,http://dx.doi.org/10.1371/journal.pone.0225576,PMC6890219,31794551,CC BY,"As infectious disease outbreaks emerge, public health agencies often enact vaccination and social distancing measures to slow transmission. Their success depends on not only strategies and resources, but also public adherence. Individual willingness to take precautions may be influenced by global factors, such as news media, or local factors, such as infected family members or friends. Here, we compare three modes of epidemiological decision-making in the midst of a growing outbreak using network-based mathematical models that capture plausible heterogeneity in human contact patterns. Individuals decide whether to adopt a recommended intervention based on overall disease prevalence, the proportion of social contacts infected, or the number of social contacts infected. While all strategies can substantially mitigate transmission, vaccinating (or self isolating) based on the number of infected acquaintances is expected to prevent the most infections while requiring the fewest intervention resources. Unlike the other strategies, it has a substantial herd effect, providing indirect protection to a large fraction of the population.",2019 Dec 3,"['Herrera-Diestra, José L.', 'Meyers, Lauren Ancel']",PLoS One,,,True
9be8c80283a7fed59057d7788eb2850708f45450,PMC,Curcumin to Promote the Synthesis of Silver NPs and their Self-Assembly with a Thermoresponsive Polymer in Core-Shell Nanohybrids,http://dx.doi.org/10.1038/s41598-019-54752-4,PMC6890765,31796864,CC BY,"This work presents a simple one-pot protocol to achieve core-doped shell nanohybrids comprising silver nanoparticles, curcumin and thermoresponsive polymeric shell taking advantage of the reducing properties of phenolic curcumin substance and its ability to decorate metallic surfaces. Silver nanoparticles were synthesized, via sodium citrate and silver nitrate addition into a boiling aqueous solution of curcumin, monomers and surfactant. Curcumin and sodium citrate promoted silver nucleation, acting as reducing and stabilizing agents. These curcumin-capped AgNPs enabled, after adding the radical polymerization initiator, the assembling of the growing polymer chains around the hydrophobic AgNP surface. The resultant core-doped shell nanohybrids exhibit plasmonic, luminescent and volume thermoresponsive properties, with improved possibilities to be used as successful therapeutic platforms. In fact, the possibility to nanoconfine the synergistic antioxidant, antiviral, antibacterial features of silver and curcumin in one bioavailable hybrid paves the way to promising applications in the biomedical field.",2019 Dec 3,"['Soto-Quintero, Albanelly', 'Guarrotxena, Nekane', 'García, Olga', 'Quijada-Garrido, Isabel']",Sci Rep,,,True
f635dd0f13ee3859c7e4b653398c9b9dba9895d8,PMC,Evaluation of antiviral activity of Bacillus licheniformis-fermented products against porcine epidemic diarrhea virus,http://dx.doi.org/10.1186/s13568-019-0916-0,PMC6890879,31797149,CC BY,"Bacillus licheniformis (B. licheniformis) is commonly used as probiotic and its secondary metabolites are attractive anti-microbial candidate. In the present study, we aimed to evaluate the antiviral activity of crude extracts from B. licheniformis against porcine epidemic diarrhea virus (PEDV), a highly contagious enveloped porcine virus that has caused great economic loss in pigs. In vivo, PEDV-infected piglets supplemented with air-dried solid state fermentative cultivate containing B. licheniformis-fermented products (BLFP) showed milder clinical symptoms and decreased viral shedding. Importantly, no significant systemic pathological lesions and no reduction in average daily gain were noted in pigs supplemented with the BLFP, which suggests that it is safe for use in pigs. In vitro experiments revealed that while B. licheniformis crude extracts exhibited no toxicity in Vero cells, co-cultivation of B. licheniformis crude extracts with PEDV significantly reduced viral infection and replication. Summarized current results suggest that the B. licheniformis-fermented products could be a novel candidate food additive for reducing the impact of PED on the swine industry.",2019 Dec 3,"['Peng, Ju-Yi', 'Horng, Yi-Bing', 'Wu, Ching-Ho', 'Chang, Chia-Yu', 'Chang, Yen-Chen', 'Tsai, Pei-Shiue', 'Jeng, Chian-Ren', 'Cheng, Yeong-Hsiang', 'Chang, Hui-Wen']",AMB Express,,,True
2448743a5de075f6a1816e46fe72b69cc791da18,PMC,"Expression of 9-O- and 7,9-O-Acetyl Modified Sialic Acid in Cells and Their Effects on Influenza Viruses",http://dx.doi.org/10.1128/mBio.02490-19,PMC6890989,31796537,CC BY,"Sialic acids (Sia) are widely displayed on the surfaces of cells and tissues. Sia come in a variety of chemically modified forms, including those with acetyl modifications at the C-7, C-8, and C-9 positions. Here, we analyzed the distribution and amounts of these acetyl modifications in different human and canine cells. Since Sia or their variant forms are receptors for influenza A, B, C, and D viruses, we examined the effects of these modifications on virus infections. We confirmed that 9-O-acetyl and 7,9-O-acetyl modified Sia are widely but variably expressed across cell lines from both humans and canines. Although they were expressed on the cell surfaces of canine MDCK cell lines, they were located primarily within the Golgi compartment of human HEK-293 and A549 cells. The O-acetyl modified Sia were expressed at low levels of 1 to 2% of total Sia in these cell lines. We knocked out and overexpressed the sialate O-acetyltransferase gene (CasD1) and knocked out the sialate O-acetylesterase gene (SIAE) using CRISPR/Cas9 editing. Knocking out CasD1 removed 7,9-O- and 9-O-acetyl Sia expression, confirming previous reports. However, overexpression of CasD1 and knockout of SIAE gave only modest increases in 9-O-acetyl levels in cells and no change in 7,9-O-acetyl levels, indicating that there are complex regulations of these modifications. These modifications were essential for influenza C and D infection but had no obvious effect on influenza A and B infection.",2019 Dec 3,"['Barnard, Karen N.', 'Wasik, Brian R.', 'LaClair, Justin R.', 'Buchholz, David W.', 'Weichert, Wendy S.', 'Alford-Lawrence, Brynn K.', 'Aguilar, Hector C.', 'Parrish, Colin R.']",mBio,,,True
1e912d2c58583bb9540a560d237fca233aefde70,PMC,"Biotechnological Potential of Bacteria Isolated from the Sea Cucumber Holothuria leucospilota and Stichopus vastus from Lampung, Indonesia",http://dx.doi.org/10.3390/md17110635,PMC6891442,31717405,CC BY,"In order to minimize re-discovery of already known anti-infective compounds, we focused our screening approach on understudied, almost untapped marine environments including marine invertebrates and their associated bacteria. Therefore, two sea cucumber species, Holothuria leucospilota and Stichopus vastus, were collected from Lampung (Indonesia), and 127 bacterial strains were identified by partial 16S rRNA-gene sequencing analysis and compared with the NCBI database. In addition, the overall bacterial diversity from tissue samples of the sea cucumbers H. leucospilota and S. vastus was analyzed using the cultivation-independent Illumina MiSEQ analysis. Selected bacterial isolates were grown to high densities and the extracted biomass was tested against a selection of bacteria and fungi as well as the hepatitis C virus (HCV). Identification of putative bioactive bacterial-derived compounds were performed by analyzing the accurate mass of the precursor/parent ions (MS(1)) as well as product/daughter ions (MS(2)) using high resolution mass spectrometry (HRMS) analysis of all active fractions. With this attempt we were able to identify 23 putatively known and two previously unidentified precursor ions. Moreover, through 16S rRNA-gene sequencing we were able to identify putatively novel bacterial species from the phyla Actinobacteria, Proteobacteria and also Firmicutes. Our findings suggest that sea cucumbers like H. leucospilota and S. vastus are promising sources for the isolation of novel bacterial species that produce compounds with potentially high biotechnological potential.",2019 Nov 8,"['Wibowo, Joko T.', 'Kellermann, Matthias Y.', 'Versluis, Dennis', 'Putra, Masteria Y.', 'Murniasih, Tutik', 'Mohr, Kathrin I.', 'Wink, Joachim', 'Engelmann, Michael', 'Praditya, Dimas F.', 'Steinmann, Eike', 'Schupp, Peter J.']",Mar Drugs,,,True
cf997a9d856f8c044b352dad4b62e6718fbe93d3,PMC,"Biotechnological Potential of Bacteria Isolated from the Sea Cucumber Holothuria leucospilota and Stichopus vastus from Lampung, Indonesia",http://dx.doi.org/10.3390/md17110635,PMC6891442,31717405,CC BY,"In order to minimize re-discovery of already known anti-infective compounds, we focused our screening approach on understudied, almost untapped marine environments including marine invertebrates and their associated bacteria. Therefore, two sea cucumber species, Holothuria leucospilota and Stichopus vastus, were collected from Lampung (Indonesia), and 127 bacterial strains were identified by partial 16S rRNA-gene sequencing analysis and compared with the NCBI database. In addition, the overall bacterial diversity from tissue samples of the sea cucumbers H. leucospilota and S. vastus was analyzed using the cultivation-independent Illumina MiSEQ analysis. Selected bacterial isolates were grown to high densities and the extracted biomass was tested against a selection of bacteria and fungi as well as the hepatitis C virus (HCV). Identification of putative bioactive bacterial-derived compounds were performed by analyzing the accurate mass of the precursor/parent ions (MS(1)) as well as product/daughter ions (MS(2)) using high resolution mass spectrometry (HRMS) analysis of all active fractions. With this attempt we were able to identify 23 putatively known and two previously unidentified precursor ions. Moreover, through 16S rRNA-gene sequencing we were able to identify putatively novel bacterial species from the phyla Actinobacteria, Proteobacteria and also Firmicutes. Our findings suggest that sea cucumbers like H. leucospilota and S. vastus are promising sources for the isolation of novel bacterial species that produce compounds with potentially high biotechnological potential.",2019 Nov 8,"['Wibowo, Joko T.', 'Kellermann, Matthias Y.', 'Versluis, Dennis', 'Putra, Masteria Y.', 'Murniasih, Tutik', 'Mohr, Kathrin I.', 'Wink, Joachim', 'Engelmann, Michael', 'Praditya, Dimas F.', 'Steinmann, Eike', 'Schupp, Peter J.']",Mar Drugs,,,True
8a2ca0a9b9108a56a79d6a610c6537102c124697,PMC,Novel Isoxazolidine and γ-Lactam Analogues of Homonucleosides,http://dx.doi.org/10.3390/molecules24224014,PMC6891762,31698778,CC BY,"Homonucleoside analogues cis-16 and trans-17 having a (5-methoxycarbonyl)isoxazolidine framework were synthesized via the 1,3-dipolar cycloaddition of nucleobase-derived nitrones with methyl acrylate. Hydrogenolysis of the isoxazolidines containing thymine, dihydrouracil, theophylline and adenine moieties efficiently led to the formation of the respective γ-lactam analogues. γ-Lactam analogues having 5-bromouracil and 5-chlorouracil fragments were synthesized by treatment of uracil-containing γ-lactams with NBS and NCS. Isoxazolidine and γ-lactam analogues of homonucleosides obtained herein were evaluated for activity against a broad range of DNA and RNA viruses. None of the compounds that were tested exhibited antiviral or cytotoxic activity at concentrations up to 100 µM. The cytostatic activities of all compounds toward nine cancerous cell lines was tested. γ-Lactams trans-15e (Cl-Ura) and cis-15h (Theo) appeared the most active toward pancreatic adenocarcinoma cells (Capan-1), showing IC(50) values 21.5 and 18.2 µM, respectively. Isoxazolidine cis-15e (Cl-Ura) inhibited the proliferation of colorectal carcinoma (HCT-116).",2019 Nov 6,"['Piotrowska, Dorota G.', 'Głowacka, Iwona E.', 'Schols, Dominique', 'Snoeck, Robert', 'Andrei, Graciela', 'Gotkowska, Joanna']",Molecules,,,True
7037e1fbb04e2f1299b12d0f5c7ee9a6d6c8973f,PMC,Novel Isoxazolidine and γ-Lactam Analogues of Homonucleosides,http://dx.doi.org/10.3390/molecules24224014,PMC6891762,31698778,CC BY,"Homonucleoside analogues cis-16 and trans-17 having a (5-methoxycarbonyl)isoxazolidine framework were synthesized via the 1,3-dipolar cycloaddition of nucleobase-derived nitrones with methyl acrylate. Hydrogenolysis of the isoxazolidines containing thymine, dihydrouracil, theophylline and adenine moieties efficiently led to the formation of the respective γ-lactam analogues. γ-Lactam analogues having 5-bromouracil and 5-chlorouracil fragments were synthesized by treatment of uracil-containing γ-lactams with NBS and NCS. Isoxazolidine and γ-lactam analogues of homonucleosides obtained herein were evaluated for activity against a broad range of DNA and RNA viruses. None of the compounds that were tested exhibited antiviral or cytotoxic activity at concentrations up to 100 µM. The cytostatic activities of all compounds toward nine cancerous cell lines was tested. γ-Lactams trans-15e (Cl-Ura) and cis-15h (Theo) appeared the most active toward pancreatic adenocarcinoma cells (Capan-1), showing IC(50) values 21.5 and 18.2 µM, respectively. Isoxazolidine cis-15e (Cl-Ura) inhibited the proliferation of colorectal carcinoma (HCT-116).",2019 Nov 6,"['Piotrowska, Dorota G.', 'Głowacka, Iwona E.', 'Schols, Dominique', 'Snoeck, Robert', 'Andrei, Graciela', 'Gotkowska, Joanna']",Molecules,,,False
b9636d270e8b284dc94c0e372004e24ce85f2340,PMC,"Middle East respiratory syndrome coronavirus (MERS-CoV) neutralising antibodies in a high-risk human population, Morocco, November 2017 to January 2018",http://dx.doi.org/10.2807/1560-7917.ES.2019.24.48.1900244,PMC6891945,31796154,CC BY,"BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) remains a major concern for global public health. Dromedaries are the source of human zoonotic infection. MERS-CoV is enzootic among dromedaries on the Arabian Peninsula, the Middle East and in Africa. Over 70% of infected dromedaries are found in Africa. However, all known zoonotic cases of MERS have occurred in the Arabian Peninsula with none being reported in Africa. AIM: We aimed to investigate serological evidence of MERS-CoV infection in humans living in camel-herding areas in Morocco to provide insights on whether zoonotic transmission is taking place. METHODS: We carried out a cross sectional seroprevalence study from November 2017 through January 2018. We adapted a generic World Health Organization MERS-CoV questionnaire and protocol to assess demographic and risk factors of infection among a presumed high-risk population. ELISA, MERS-CoV spike pseudoparticle neutralisation tests (ppNT) and plaque neutralisation tests (PRNT) were used to assess MERS-CoV seropositivity. RESULTS: Serum samples were collected from camel slaughterhouse workers (n = 137), camel herders (n = 156) and individuals of the general population without occupational contact with camels but living in camel herding areas (n = 186). MERS-CoV neutralising antibodies with ≥ 90% reduction of plaque numbers were detected in two (1.5%) slaughterhouse workers, none of the camel herders and one individual from the general population (0.5%). CONCLUSIONS: This study provides evidence of zoonotic transmission of MERS-CoV in Morocco in people who have direct or indirect exposure to dromedary camels.",2019 Nov 28,"['Abbad, Anass', 'Perera, Ranawaka APM', 'Anga, Latifa', 'Faouzi, Abdellah', 'Minh, Nhu Nguyen Tran', 'Malik, Sk Md Mamunur Rahman', 'Iounes, Nadia', 'Maaroufi, Abderrahmane', 'Van Kerkhove, Maria D', 'Peiris, Malik', 'Nourlil, Jalal']",Euro Surveill,,,False
290c2714886f1aaa00c374d3315381b0f0aa8033,PMC,"Middle East respiratory syndrome coronavirus (MERS-CoV) neutralising antibodies in a high-risk human population, Morocco, November 2017 to January 2018",http://dx.doi.org/10.2807/1560-7917.ES.2019.24.48.1900244,PMC6891945,31796154,CC BY,"BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) remains a major concern for global public health. Dromedaries are the source of human zoonotic infection. MERS-CoV is enzootic among dromedaries on the Arabian Peninsula, the Middle East and in Africa. Over 70% of infected dromedaries are found in Africa. However, all known zoonotic cases of MERS have occurred in the Arabian Peninsula with none being reported in Africa. AIM: We aimed to investigate serological evidence of MERS-CoV infection in humans living in camel-herding areas in Morocco to provide insights on whether zoonotic transmission is taking place. METHODS: We carried out a cross sectional seroprevalence study from November 2017 through January 2018. We adapted a generic World Health Organization MERS-CoV questionnaire and protocol to assess demographic and risk factors of infection among a presumed high-risk population. ELISA, MERS-CoV spike pseudoparticle neutralisation tests (ppNT) and plaque neutralisation tests (PRNT) were used to assess MERS-CoV seropositivity. RESULTS: Serum samples were collected from camel slaughterhouse workers (n = 137), camel herders (n = 156) and individuals of the general population without occupational contact with camels but living in camel herding areas (n = 186). MERS-CoV neutralising antibodies with ≥ 90% reduction of plaque numbers were detected in two (1.5%) slaughterhouse workers, none of the camel herders and one individual from the general population (0.5%). CONCLUSIONS: This study provides evidence of zoonotic transmission of MERS-CoV in Morocco in people who have direct or indirect exposure to dromedary camels.",2019 Nov 28,"['Abbad, Anass', 'Perera, Ranawaka APM', 'Anga, Latifa', 'Faouzi, Abdellah', 'Minh, Nhu Nguyen Tran', 'Malik, Sk Md Mamunur Rahman', 'Iounes, Nadia', 'Maaroufi, Abderrahmane', 'Van Kerkhove, Maria D', 'Peiris, Malik', 'Nourlil, Jalal']",Euro Surveill,,,True
3083af632db7cfbddd6ac1b939fcf076d545e783,PMC,Portable sequencer in the fight against infectious disease,http://dx.doi.org/10.1038/s10038-019-0675-4,PMC6892364,31582773,CC BY,"Infectious disease is still a major threat in the world today. Five decades ago, it was considered soon to be eradicated, but the adaptation of pathogens to environmental pressure, such as antimicrobials, encouraged the emergence and reemergence of infectious disease. The fight with infectious disease starts with prevention, diagnosis, and treatment. Diagnosis can be upheld by observing the cause of disease under the microscope or detecting the presence of nucleic acid and proteins of the pathogens. The molecular techniques span from classical polymerase chain reaction (PCR) to sequencing the nucleic acid composition. Here, we are reviewing the works have been undertaken to utilize a portable sequencer, MinION, in various aspects of infectious disease management.",2020 Oct 3,"['Mongan, Arthur Elia', 'Tuda, Josef Sem Berth', 'Runtuwene, Lucky Ronald']",J Hum Genet,,,True
d5d29d1d48e1a4fe8f39d38639766c86dc976e5e,PMC,Factors that enable effective One Health collaborations - A scoping review of the literature,http://dx.doi.org/10.1371/journal.pone.0224660,PMC6892547,31800579,CC BY,"Advocates for a One Health approach recognize that global health challenges require multidisciplinary collaborative efforts. While past publications have looked at interdisciplinary competency training for collaboration, few have identified the factors and conditions that enable operational One Health. Through a scoping review of the literature, a multidisciplinary team of researchers analyzed peer-reviewed publications describing multisectoral collaborations around infectious disease-related health events. The review identified 12 factors that support successful One Health collaborations and a coordinated response to health events across three levels: two individual factors (education & training and prior experience & existing relationships), four organizational factors (organizational structures, culture, human resources and, communication), and six network factors (network structures, relationships, leadership, management, available & accessible resources, political environment). The researchers also identified the stage of collaboration during which these factors were most critical, further organizing into starting condition or process-based factors. The research found that publications on multisectoral collaboration for health events do not uniformly report on successes or challenges of collaboration and rarely identify outputs or outcomes of the collaborative process. This paper proposes a common language and framework to enable more uniform reporting, implementation, and evaluation of future One Health collaborations.",2019 Dec 4,"['Errecaborde, Kaylee Myhre', 'Macy, Katelyn Wuebbolt', 'Pekol, Amy', 'Perez, Sol', 'O’Brien, Mary Katherine', 'Allen, Ian', 'Contadini, Francesca', 'Lee, Julia Yeri', 'Mumford, Elizabeth', 'Bender, Jeff B.', 'Pelican, Katharine']",PLoS One,,,True
a9f1cb393010b269321cb82a569379a5af380a89,PMC,Measuring Similarity among Protein Sequences Using a New Descriptor,http://dx.doi.org/10.1155/2019/2796971,PMC6893242,31886192,CC BY,"The comparison of protein sequences according to similarity is a fundamental aspect of today's biomedical research. With the developments of sequencing technologies, a large number of protein sequences increase exponentially in the public databases. Famous sequences' comparison methods are alignment based. They generally give excellent results when the sequences under study are closely related and they are time consuming. Herein, a new alignment-free method is introduced. Our technique depends on a new graphical representation and descriptor. The graphical representation of protein sequence is a simple way to visualize protein sequences. The descriptor compresses the primary sequence into a single vector composed of only two values. Our approach gives good results with both short and long sequences within a little computation time. It is applied on nine beta globin, nine ND5 (NADH dehydrogenase subunit 5), and 24 spike protein sequences. Correlation and significance analyses are also introduced to compare our similarity/dissimilarity results with others' approaches, results, and sequence homology.",2019 Nov 22,"['Abo-Elkhier, Mervat M.', 'Abd Elwahaab, Marwa A.', 'Abo El Maaty, Moheb I.']",Biomed Res Int,,,True
de876ac85313b4495ef6f7292ad5cc77cbd1880e,PMC,Erythromycin Estolate Inhibits Zika Virus Infection by Blocking Viral Entry as a Viral Inactivator,http://dx.doi.org/10.3390/v11111064,PMC6893414,31731598,CC BY,"Recently, Zika virus (ZIKV) has attracted much attention in consideration of its association with severe neurological complications including fetal microcephaly. However, there are currently no prophylactic vaccines or therapeutic drugs approved for clinical treatments of ZIKV infection. To determine the potential anti-ZIKV inhibitors, we screened a library of clinical drugs with good safety profiles. Erythromycin estolate (Ery-Est), one of the macrolide antibiotics, was found to effectively inhibit ZIKV infection in different cell types and significantly protect A129 mice from ZIKV-associated neurological signs and mortality. Through further investigation, Ery-Est was verified to inhibit ZIKV entry by disrupting the integrity of the viral membrane which resulted in the loss of ZIKV infectivity. Furthermore, Ery-Est also showed inhibitory activity against dengue virus (DENV) and yellow fever virus (YFV). Thus, Ery-Est may be a promising drug for patients with ZIKV infection, particularly pregnant women.",2019 Nov 15,"['Wang, Xiaohuan', 'Xia, Shuai', 'Zou, Peng', 'Lu, Lu']",Viruses,,,True
16567d4215695851731265d8bf15f445553bc6ae,PMC,Erythromycin Estolate Inhibits Zika Virus Infection by Blocking Viral Entry as a Viral Inactivator,http://dx.doi.org/10.3390/v11111064,PMC6893414,31731598,CC BY,"Recently, Zika virus (ZIKV) has attracted much attention in consideration of its association with severe neurological complications including fetal microcephaly. However, there are currently no prophylactic vaccines or therapeutic drugs approved for clinical treatments of ZIKV infection. To determine the potential anti-ZIKV inhibitors, we screened a library of clinical drugs with good safety profiles. Erythromycin estolate (Ery-Est), one of the macrolide antibiotics, was found to effectively inhibit ZIKV infection in different cell types and significantly protect A129 mice from ZIKV-associated neurological signs and mortality. Through further investigation, Ery-Est was verified to inhibit ZIKV entry by disrupting the integrity of the viral membrane which resulted in the loss of ZIKV infectivity. Furthermore, Ery-Est also showed inhibitory activity against dengue virus (DENV) and yellow fever virus (YFV). Thus, Ery-Est may be a promising drug for patients with ZIKV infection, particularly pregnant women.",2019 Nov 15,"['Wang, Xiaohuan', 'Xia, Shuai', 'Zou, Peng', 'Lu, Lu']",Viruses,,,False
d3618a7956fc136c7183df5b9c665e96a3df8748,PMC,The Porcine Deltacoronavirus Replication Organelle Comprises Double-Membrane Vesicles and Zippered Endoplasmic Reticulum with Double-Membrane Spherules,http://dx.doi.org/10.3390/v11111030,PMC6893519,31694296,CC BY,"Porcine deltacoronavirus (PDCoV) was first identified in Hong Kong in 2012 from samples taken from pigs in 2009. PDCoV was subsequently identified in the USA in 2014 in pigs with a history of severe diarrhea. The virus has now been detected in pigs in several countries around the world. Following the development of tissue culture adapted strains of PDCoV, it is now possible to address questions regarding virus–host cell interactions for this genera of coronavirus. Here, we presented a detailed study of PDCoV-induced replication organelles. All positive-strand RNA viruses induce the rearrangement of cellular membranes during virus replication to support viral RNA synthesis, forming the replication organelle. Replication organelles for the Alpha-, Beta-, and Gammacoronavirus genera have been characterized. All coronavirus genera induced the formation of double-membrane vesicles (DMVs). In addition, Alpha- and Betacoronaviruses induce the formation of convoluted membranes, while Gammacoronaviruses induce the formation of zippered endoplasmic reticulum (ER) with tethered double-membrane spherules. However, the structures induced by Deltacoronaviruses, particularly the presence of convoluted membranes or double-membrane spherules, are unknown. Initially, the dynamics of PDCoV strain OH-FD22 replication were assessed with the onset of viral RNA synthesis, protein synthesis, and progeny particle release determined. Subsequently, virus-induced membrane rearrangements were identified in infected cells by electron microscopy. As has been observed for all other coronaviruses studied to date, PDCoV replication was found to induce the formation of double-membrane vesicles. Significantly, however, PDCoV replication was also found to induce the formation of regions of zippered endoplasmic reticulum, small associated tethered vesicles, and double-membrane spherules. These structures strongly resemble the replication organelle induced by avian Gammacoronavirus infectious bronchitis virus.",2019 Nov 5,"['Doyle, Nicole', 'Hawes, Philippa C.', 'Simpson, Jennifer', 'Adams, Lorin H.', 'Maier, Helena J.']",Viruses,,,True
7a37bc3345060483c49b12bc1db7982573c313be,PMC,Delmarva (DMV/1639) Infectious Bronchitis Virus (IBV) Variants Isolated in Eastern Canada Show Evidence of Recombination,http://dx.doi.org/10.3390/v11111054,PMC6893544,31766215,CC BY,"Infectious bronchitis virus (IBV) infection in chickens can lead to an economically important disease, namely, infectious bronchitis (IB). New IBV variants are continuously emerging, which complicates vaccination-based IB control. In this study, five IBVs were isolated from clinical samples submitted to a diagnostic laboratory in Ontario, Canada, and subjected to detailed molecular characterization. Analysis of the spike (S)1 gene showed that these five IBVs were highly related to the Delmarva (DMV/1639) strain (~97.0% nucleotide sequence similarity) that was firstly isolated from an IB outbreak in the Delmarva peninsula, United States of America (USA), in 2011. However, the complete genomic sequence analysis showed a 93.5–93.7% similarity with the Connecticut (Conn) vaccine strain, suggesting that Conn-like viruses contributed to the evolution of the five Canadian IBV/DMV isolates. A SimPlot analysis of the complete genomic sequence showed evidence of recombination for at least three different IBV strains, including a Conn vaccine-like strain, a 4/91 vaccine-like strain, and one strain that is yet-unidentified. The unidentified strain may have contributed the genomic regions of the S, 3, and membrane (M) genes of the five Canadian IBV/DMV isolates. The study outcomes add to the existing knowledge about involvement of recombination in IBV evolution.",2019 Nov 13,"['Hassan, Mohamed S. H.', 'Ojkic, Davor', 'Coffin, Carla S.', 'Cork, Susan C.', 'van der Meer, Frank', 'Abdul-Careem, Mohamed Faizal']",Viruses,,,True
e60ee94e2aa5025dab4f452cd2b3ce2325f68feb,PMC,Delmarva (DMV/1639) Infectious Bronchitis Virus (IBV) Variants Isolated in Eastern Canada Show Evidence of Recombination,http://dx.doi.org/10.3390/v11111054,PMC6893544,31766215,CC BY,"Infectious bronchitis virus (IBV) infection in chickens can lead to an economically important disease, namely, infectious bronchitis (IB). New IBV variants are continuously emerging, which complicates vaccination-based IB control. In this study, five IBVs were isolated from clinical samples submitted to a diagnostic laboratory in Ontario, Canada, and subjected to detailed molecular characterization. Analysis of the spike (S)1 gene showed that these five IBVs were highly related to the Delmarva (DMV/1639) strain (~97.0% nucleotide sequence similarity) that was firstly isolated from an IB outbreak in the Delmarva peninsula, United States of America (USA), in 2011. However, the complete genomic sequence analysis showed a 93.5–93.7% similarity with the Connecticut (Conn) vaccine strain, suggesting that Conn-like viruses contributed to the evolution of the five Canadian IBV/DMV isolates. A SimPlot analysis of the complete genomic sequence showed evidence of recombination for at least three different IBV strains, including a Conn vaccine-like strain, a 4/91 vaccine-like strain, and one strain that is yet-unidentified. The unidentified strain may have contributed the genomic regions of the S, 3, and membrane (M) genes of the five Canadian IBV/DMV isolates. The study outcomes add to the existing knowledge about involvement of recombination in IBV evolution.",2019 Nov 13,"['Hassan, Mohamed S. H.', 'Ojkic, Davor', 'Coffin, Carla S.', 'Cork, Susan C.', 'van der Meer, Frank', 'Abdul-Careem, Mohamed Faizal']",Viruses,,,False
76f55ebed6baf41823e8d40954a7e2a62e244109,PMC,Identification of a Novel Betacoronavirus (Merbecovirus) in Amur Hedgehogs from China,http://dx.doi.org/10.3390/v11110980,PMC6893546,31653070,CC BY,"While dromedaries are the immediate animal source of Middle East Respiratory Syndrome (MERS) epidemic, viruses related to MERS coronavirus (MERS-CoV) have also been found in bats as well as hedgehogs. To elucidate the evolution of MERS-CoV-related viruses and their interspecies transmission pathway, samples were collected from different mammals in China. A novel coronavirus related to MERS-CoV, Erinaceus amurensis hedgehog coronavirus HKU31 (Ea-HedCoV HKU31), was identified from two Amur hedgehogs. Genome analysis supported that Ea-HedCoV HKU31 represents a novel species under Merbecovirus, being most closely related to Erinaceus CoV from European hedgehogs in Germany, with 79.6% genome sequence identity. Compared to other members of Merbecovirus, Ea-HedCoV HKU31 possessed unique non-structural proteins and putative cleavage sites at ORF1ab. Phylogenetic analysis showed that Ea-HedCoV HKU31 and BetaCoV Erinaceus/VMC/DEU/2012 were closely related to NeoCoV and BatCoV PREDICT from African bats in the spike region, suggesting that the latter bat viruses have arisen from recombination between CoVs from hedgehogs and bats. The predicted HKU31 receptor-binding domain (RBD) possessed only one out of 12 critical amino acid residues for binding to human dipeptidyl peptidase 4 (hDPP4), the MERS-CoV receptor. The structural modeling of the HKU31-RBD-hDPP4 binding interphase compared to that of MERS-CoV and Tylonycteris bat CoV HKU4 (Ty-BatCoV HKU4) suggested that HKU31-RBD is unlikely to bind to hDPP4. Our findings support that hedgehogs are an important reservoir of Merbecovirus, with evidence of recombination with viruses from bats. Further investigations in bats, hedgehogs and related animals are warranted to understand the evolution of MERS-CoV-related viruses.",2019 Oct 24,"['Lau, Susanna K. P.', 'Luk, Hayes K. H.', 'Wong, Antonio C. P.', 'Fan, Rachel Y. Y.', 'Lam, Carol S. F.', 'Li, Kenneth S. M.', 'Ahmed, Syed Shakeel', 'Chow, Franklin W.N.', 'Cai, Jian-Piao', 'Zhu, Xun', 'Chan, Jasper F. W.', 'Lau, Terrence C. K.', 'Cao, Kaiyuan', 'Li, Mengfeng', 'Woo, Patrick C. Y.', 'Yuen, Kwok-Yung']",Viruses,,,True
b857b9b22da00757e3b4804917a89625462be049,PMC,Identification of a Novel Betacoronavirus (Merbecovirus) in Amur Hedgehogs from China,http://dx.doi.org/10.3390/v11110980,PMC6893546,31653070,CC BY,"While dromedaries are the immediate animal source of Middle East Respiratory Syndrome (MERS) epidemic, viruses related to MERS coronavirus (MERS-CoV) have also been found in bats as well as hedgehogs. To elucidate the evolution of MERS-CoV-related viruses and their interspecies transmission pathway, samples were collected from different mammals in China. A novel coronavirus related to MERS-CoV, Erinaceus amurensis hedgehog coronavirus HKU31 (Ea-HedCoV HKU31), was identified from two Amur hedgehogs. Genome analysis supported that Ea-HedCoV HKU31 represents a novel species under Merbecovirus, being most closely related to Erinaceus CoV from European hedgehogs in Germany, with 79.6% genome sequence identity. Compared to other members of Merbecovirus, Ea-HedCoV HKU31 possessed unique non-structural proteins and putative cleavage sites at ORF1ab. Phylogenetic analysis showed that Ea-HedCoV HKU31 and BetaCoV Erinaceus/VMC/DEU/2012 were closely related to NeoCoV and BatCoV PREDICT from African bats in the spike region, suggesting that the latter bat viruses have arisen from recombination between CoVs from hedgehogs and bats. The predicted HKU31 receptor-binding domain (RBD) possessed only one out of 12 critical amino acid residues for binding to human dipeptidyl peptidase 4 (hDPP4), the MERS-CoV receptor. The structural modeling of the HKU31-RBD-hDPP4 binding interphase compared to that of MERS-CoV and Tylonycteris bat CoV HKU4 (Ty-BatCoV HKU4) suggested that HKU31-RBD is unlikely to bind to hDPP4. Our findings support that hedgehogs are an important reservoir of Merbecovirus, with evidence of recombination with viruses from bats. Further investigations in bats, hedgehogs and related animals are warranted to understand the evolution of MERS-CoV-related viruses.",2019 Oct 24,"['Lau, Susanna K. P.', 'Luk, Hayes K. H.', 'Wong, Antonio C. P.', 'Fan, Rachel Y. Y.', 'Lam, Carol S. F.', 'Li, Kenneth S. M.', 'Ahmed, Syed Shakeel', 'Chow, Franklin W.N.', 'Cai, Jian-Piao', 'Zhu, Xun', 'Chan, Jasper F. W.', 'Lau, Terrence C. K.', 'Cao, Kaiyuan', 'Li, Mengfeng', 'Woo, Patrick C. Y.', 'Yuen, Kwok-Yung']",Viruses,,,False
ff03bab2cb87384f817f827dd9331ac2d3cea67d,PMC,Characterization and Pathogenicity of the Porcine Deltacoronavirus Isolated in Southwest China,http://dx.doi.org/10.3390/v11111074,PMC6893596,31752115,CC BY,"Porcine deltacoronavirus (PDCoV) is a newly emerging enteric pathogen in swine that causes diarrhea in neonatal piglets and creates an additional economic burden on porcine industries in Asia and North America. In this study, a PDCoV isolate, CHN-SC2015, was isolated from Sichuan Province in southwest China. The isolate was characterized by a cytopathic effect, immunofluorescence, and electron microscopy. CHN-SC2015 titers in LLC-PK cells ranged from 10(4.31) to 10(8.22) TCID(50)/mL during the first 30 passages. During serial passage, 11 nucleotide mutations occurred in the S gene, resulting in nine amino acid changes. A whole genome sequencing analysis demonstrated that CHN-SC2015 shares 97.5%–99.1% identity with 59 reference strains in GenBank. Furthermore, CHN-SC2015 contained 6-nt deletion and 9-nt insertion in the ORF1ab gene, 3-nt deletion in the S gene and 11-nt deletion in its 3′UTR compared with other reference strains available in GenBank. A phylogenetic analysis showed that CHN-SC2015 is more closely related to other PDCoV strains in China than to the strains from Southeast Asia, USA, Japan, and South Korea, indicating the diversity of genetic relationships and regional and epidemic characteristics among these strains. A recombination analysis indicated that CHN-SC2015 experienced recombination events between SHJS/SL/2016 and TT-1115. In vivo infection demonstrated that CHN-SC2015 is highly pathogenic to sucking piglets, causing diarrhea, vomiting, dehydration, and death. Virus was shed daily in the feces of infected piglets and upon necropsy, was found distributed in the gastrointestinal tract and in multiple organs. CHN-SC2015 is the first systematically characterized strain from southwest China hitherto reported. Our results enrich the body of information on the epidemiology, pathogenicity and molecular evolution associated with PDCoV.",2019 Nov 18,"['Zhao, Yujia', 'Qu, Huan', 'Hu, Jingfei', 'Fu, Jiayu', 'Chen, Rui', 'Li, Cheng', 'Cao, Sanjie', 'Wen, Yiping', 'Wu, Rui', 'Zhao, Qin', 'Yan, Qigui', 'Wen, Xintian', 'Huang, Xiaobo']",Viruses,,,True
aa05b23cbdb62abd6dc349744370d9338a2f4e21,PMC,Isolation and Characterization of Clinical RSV Isolates in Belgium during the Winters of 2016–2018,http://dx.doi.org/10.3390/v11111031,PMC6893609,31698728,CC BY,"Respiratory Syncytial Virus (RSV) is a very important viral pathogen in children, immunocompromised and cardiopulmonary diseased patients and the elderly. Most of the published research with RSV was performed on RSV Long and RSV A2, isolated in 1956 and 1961, yet recent RSV isolates differ from these prototype strains. Additionally, these viruses have been serially passaged in cell culture, which may result in adaptations that affect virus–host interactions. We have isolated RSV from mucosal secretions of 12 patients in the winters 2016–2017 and 2017–2018, of which eight RSV-A subtypes and four RSV-B subtypes. Passage 3 of the isolates was assessed for viral replication kinetics and infectious virus production in HEp-2, A549 and BEAS-2B cells, thermal stability at 37 °C, 32 °C and 4 °C, syncytia formation, neutralization by palivizumab and mucin mRNA expression in infected A549 cells. We observed that viruses isolated in one RSV season show differences on the tested assays. Furthermore, comparison with RSV A2 and RSV B1 reveals for some RSV isolates differences in viral replication kinetics, thermal stability and fusion capacity. Major differences are, however, not observed and differences between the recent isolates and reference strains is, overall, similar to the observed variation in between the recent isolates. One clinical isolate (BE/ANT-A11/17) replicated very efficiently in all cell lines, and remarkably, even better than RSV A2 in the HEp-2 cell line.",2019 Nov 6,"['Van der Gucht, Winke', 'Stobbelaar, Kim', 'Govaerts, Matthias', 'Mangodt, Thomas', 'Barbezange, Cyril', 'Leemans, Annelies', 'De Winter, Benedicte', 'Van Gucht, Steven', 'Caljon, Guy', 'Maes, Louis', 'De Dooy, Jozef', 'Jorens, Philippe', 'Smet, Annemieke', 'Cos, Paul', 'Verhulst, Stijn', 'Delputte, Peter L.']",Viruses,,,True
e7742497150bd3dc1d60ff914d1c0fb05f747a1a,PMC,Nasal Cytokine Profiles of Patients Hospitalised with Respiratory Wheeze Associated with Rhinovirus C,http://dx.doi.org/10.3390/v11111038,PMC6893661,31703379,CC BY,"Background: Rhinovirus C is an important pathogen of asthmatic and non-asthmatic children hospitalised with episodic wheeze. Previous studies on other respiratory viruses have shown that several host cytokines correlate with duration of hospitalisation, but this has yet to be investigated in children with RV-C infection. We determined the nasal cytokine profiles of these children and investigated their relationship with RV-C load and clinical outcome. Flocked nasal swabs were collected from children aged 24–72 months presenting to the Emergency Department at Princess Margaret Hospital with a clinical diagnosis of acute wheeze and an acute upper respiratory tract viral infection. RV-C load was determined by quantitative RT-PCR and cytokine profiles were characterised by a commercial human cytokine 34-plex panel. RV-C was the most commonly detected virus in pre-school-aged children hospitalised with an episodic wheeze. RV-C load did not significantly differ between asthmatic and non-asthmatic patients. Both groups showed a Th2-based cytokine profile. However, Th17 response cytokines IL-17 and IL-1β were only elevated in RV-C-infected children with pre-existing asthma. Neither RV-C load nor any specific cytokines were associated illness severity in this study. Medically attended RV-C-induced wheeze is characterised by a Th2 inflammatory pattern, independent of viral load. Any therapeutic interventions should be aimed at modulating the host response following infection.",2019 Nov 7,"['Sikazwe, Chisha T.', 'Laing, Ingrid A.', 'Imrie, Allison', 'Smith, David W.']",Viruses,,,True
df98aa1e68c38fdd6376a6e6eac7cb9d365fe8bb,PMC,Nasal Cytokine Profiles of Patients Hospitalised with Respiratory Wheeze Associated with Rhinovirus C,http://dx.doi.org/10.3390/v11111038,PMC6893661,31703379,CC BY,"Background: Rhinovirus C is an important pathogen of asthmatic and non-asthmatic children hospitalised with episodic wheeze. Previous studies on other respiratory viruses have shown that several host cytokines correlate with duration of hospitalisation, but this has yet to be investigated in children with RV-C infection. We determined the nasal cytokine profiles of these children and investigated their relationship with RV-C load and clinical outcome. Flocked nasal swabs were collected from children aged 24–72 months presenting to the Emergency Department at Princess Margaret Hospital with a clinical diagnosis of acute wheeze and an acute upper respiratory tract viral infection. RV-C load was determined by quantitative RT-PCR and cytokine profiles were characterised by a commercial human cytokine 34-plex panel. RV-C was the most commonly detected virus in pre-school-aged children hospitalised with an episodic wheeze. RV-C load did not significantly differ between asthmatic and non-asthmatic patients. Both groups showed a Th2-based cytokine profile. However, Th17 response cytokines IL-17 and IL-1β were only elevated in RV-C-infected children with pre-existing asthma. Neither RV-C load nor any specific cytokines were associated illness severity in this study. Medically attended RV-C-induced wheeze is characterised by a Th2 inflammatory pattern, independent of viral load. Any therapeutic interventions should be aimed at modulating the host response following infection.",2019 Nov 7,"['Sikazwe, Chisha T.', 'Laing, Ingrid A.', 'Imrie, Allison', 'Smith, David W.']",Viruses,,,False
24f3fb94ffa06167fa87ba73f357916cc88359b0,PMC,Detection and Cellular Tropism of Porcine Astrovirus Type 3 on Breeding Farms,http://dx.doi.org/10.3390/v11111051,PMC6893673,31718108,CC BY,"Astroviruses cause disease in a variety of species. Yet, little is known about the epidemiology of a majority of astroviruses including porcine astrovirus type 3 (PoAstV3), which is a putative cause of polioencephalomyelitis in swine. Accordingly, a cross-sectional study was conducted on sow farms with or without reported PoAstV3-associated neurologic disease in growing pigs weaned from those farms. Additionally, a conveniently selected subset of piglets from one farm was selected for gross and histologic evaluation. The distribution of PoAstV3 in the enteric system was evaluated through in situ hybridization. PoAstV3, as detected by RT-qPCR on fecal samples, was frequently detected across sows and piglets (66–90%) on all farms (65–85%). PoAstV3 was detected subsequently at a similar detection frequency (77% vs 85%) on one farm after three months. Viral shedding, as determined by the cycle quantification value, suggests that piglets shed higher quantities of virus than adult swine. No link between gastrointestinal disease and PoAstV3 was found. However, PoAstV3 was detected by in situ in myenteric plexus neurons of piglets elucidating a possible route of spread of the virus from the gastrointestinal tract to the central nervous system. These data suggest PoAstV3 has endemic potential, is shed in the feces at greater quantities by suckling piglets when compared to sows, and infection is widespread on farms in which it is detected.",2019 Nov 12,"['Rawal, Gaurav', 'Ferreyra, Franco Matias', 'Macedo, Nubia R.', 'Bradner, Laura K.', 'Harmon, Karen M.', 'Mueller, Adam', 'Allison, Grant', 'Linhares, Daniel C.L.', 'Arruda, Bailey L.']",Viruses,,,True
3cbeb11d471dd6cebf2b65c42c00fd66a6cb5dc0,PMC,Viral Metagenomics Revealed Sendai Virus and Coronavirus Infection of Malayan Pangolins (Manis javanica),http://dx.doi.org/10.3390/v11110979,PMC6893680,31652964,CC BY,"Pangolins are endangered animals in urgent need of protection. Identifying and cataloguing the viruses carried by pangolins is a logical approach to evaluate the range of potential pathogens and help with conservation. This study provides insight into viral communities of Malayan Pangolins (Manis javanica) as well as the molecular epidemiology of dominant pathogenic viruses between Malayan Pangolin and other hosts. A total of 62,508 de novo assembled contigs were constructed, and a BLAST search revealed 3600 ones (≥300 nt) were related to viral sequences, of which 68 contigs had a high level of sequence similarity to known viruses, while dominant viruses were the Sendai virus and Coronavirus. This is the first report on the viral diversity of pangolins, expanding our understanding of the virome in endangered species, and providing insight into the overall diversity of viruses that may be capable of directly or indirectly crossing over into other mammals.",2019 Oct 24,"['Liu, Ping', 'Chen, Wu', 'Chen, Jin-Ping']",Viruses,,,True
0f93e8fef9ce127337fa00f8b16607d39c6415e8,PMC,A Multi-Omics Study of Chicken Infected by Nephropathogenic Infectious Bronchitis Virus,http://dx.doi.org/10.3390/v11111070,PMC6893681,31744152,CC BY,"Chicken gout resulting from nephropathogenic infectious bronchitis virus (NIBV) has become a serious kidney disease problem in chicken worldwide with alterations of the metabolic phenotypes in multiple metabolic pathways. To investigate the mechanisms in chicken responding to NIBV infection, we examined the global transcriptomic and metabolomic profiles of the chicken’s kidney using RNA-seq and GC–TOF/MS, respectively. Furthermore, we analyzed the alterations in cecal microorganism composition in chickens using 16S rRNA-seq. Integrated analysis of these three phenotypic datasets further managed to create correlations between the altered kidney transcriptomes and metabolome, and between kidney metabolome and gut microbiome. We found that 2868 genes and 160 metabolites were deferentially expressed or accumulated in the kidney during NIBV infection processes. These genes and metabolites were linked to NIBV-infection related processes, including immune response, signal transduction, peroxisome, purine, and amino acid metabolism. In addition, the comprehensive correlations between the kidney metabolome and cecal microbial community showed contributions of gut microbiota in the progression of NIBV-infection. Taken together, our research comprehensively describes the host responses during NIBV infection and provides new clues for further dissection of specific gene functions, metabolite affections, and the role of gut microbiota during chicken gout.",2019 Nov 16,"['Xu, Puzhi', 'Liu, Ping', 'Zhou, Changming', 'Shi, Yan', 'Wu, Qingpeng', 'Yang, Yitian', 'Li, Guyue', 'Hu, Guoliang', 'Guo, Xiaoquan']",Viruses,,,True
7d8b8767e12fc4fee2b29c6473b7dd1f3244b933,PMC,Identification of Novel Natural Products as Effective and Broad-Spectrum Anti-Zika Virus Inhibitors,http://dx.doi.org/10.3390/v11111019,PMC6893700,31684080,CC BY,"Zika virus (ZIKV) infection during pregnancy leads to severe congenital Zika syndrome, which includes microcephaly and other neurological malformations. No therapeutic agents have, so far, been approved for the treatment of ZIKV infection in humans; as such, there is a need for a continuous effort to develop effective and safe antiviral drugs to treat ZIKV-caused diseases. After screening a natural product library, we have herein identified four natural products with anti-ZIKV activity in Vero E6 cells, including gossypol, curcumin, digitonin, and conessine. Except for curcumin, the other three natural products have not been reported before to have anti-ZIKV activity. Among them, gossypol exhibited the strongest inhibitory activity against almost all 10 ZIKV strains tested, including six recent epidemic human strains. The mechanistic study indicated that gossypol could neutralize ZIKV infection by targeting the envelope protein domain III (EDIII) of ZIKV. In contrast, the other natural products inhibited ZIKV infection by targeting the host cell or cell-associated entry and replication stages of ZIKV. A combination of gossypol with any of the three natural products identified in this study, as well as with bortezomib, a previously reported anti-ZIKV compound, exhibited significant combinatorial inhibitory effects against three ZIKV human strains tested. Importantly, gossypol also demonstrated marked potency against all four serotypes of dengue virus (DENV) human strains in vitro. Taken together, this study indicates the potential for further development of these natural products, particularly gossypol, as the lead compound or broad-spectrum inhibitors against ZIKV and other flaviviruses, such as DENV.",2019 Nov 2,"['Gao, Yaning', 'Tai, Wanbo', 'Wang, Ning', 'Li, Xiang', 'Jiang, Shibo', 'Debnath, Asim K.', 'Du, Lanying', 'Chen, Shizhong']",Viruses,,,True
d11bd3933522af3dee86f26a372bb15c01e54043,PMC,Identification of Novel Natural Products as Effective and Broad-Spectrum Anti-Zika Virus Inhibitors,http://dx.doi.org/10.3390/v11111019,PMC6893700,31684080,CC BY,"Zika virus (ZIKV) infection during pregnancy leads to severe congenital Zika syndrome, which includes microcephaly and other neurological malformations. No therapeutic agents have, so far, been approved for the treatment of ZIKV infection in humans; as such, there is a need for a continuous effort to develop effective and safe antiviral drugs to treat ZIKV-caused diseases. After screening a natural product library, we have herein identified four natural products with anti-ZIKV activity in Vero E6 cells, including gossypol, curcumin, digitonin, and conessine. Except for curcumin, the other three natural products have not been reported before to have anti-ZIKV activity. Among them, gossypol exhibited the strongest inhibitory activity against almost all 10 ZIKV strains tested, including six recent epidemic human strains. The mechanistic study indicated that gossypol could neutralize ZIKV infection by targeting the envelope protein domain III (EDIII) of ZIKV. In contrast, the other natural products inhibited ZIKV infection by targeting the host cell or cell-associated entry and replication stages of ZIKV. A combination of gossypol with any of the three natural products identified in this study, as well as with bortezomib, a previously reported anti-ZIKV compound, exhibited significant combinatorial inhibitory effects against three ZIKV human strains tested. Importantly, gossypol also demonstrated marked potency against all four serotypes of dengue virus (DENV) human strains in vitro. Taken together, this study indicates the potential for further development of these natural products, particularly gossypol, as the lead compound or broad-spectrum inhibitors against ZIKV and other flaviviruses, such as DENV.",2019 Nov 2,"['Gao, Yaning', 'Tai, Wanbo', 'Wang, Ning', 'Li, Xiang', 'Jiang, Shibo', 'Debnath, Asim K.', 'Du, Lanying', 'Chen, Shizhong']",Viruses,,,False
5a2b335f389f88025ca1994a95e220479646d581,PMC,Diagnosis of Feline Infectious Peritonitis: A Review of the Current Literature,http://dx.doi.org/10.3390/v11111068,PMC6893704,31731711,CC BY,"Feline infectious peritonitis (FIP) is a fatal disease that poses several challenges for veterinarians: clinical signs and laboratory changes are non-specific, and there are two pathotypes of the etiologic agent feline coronavirus (FCoV), sometimes referred to as feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV) that vary fundamentally in their virulence, but are indistinguishable by a number of diagnostic methods. This review focuses on all important steps every veterinary practitioner has to deal with and new diagnostic tests that can be considered when encountering a cat with suspected FIP with the aim to establish a definitive diagnosis. It gives an overview on all available direct and indirect diagnostic tests and their sensitivity and specificity reported in the literature in different sample material. By providing summarized data for sensitivity and specificity of each diagnostic test and each sample material, which can easily be accessed in tables, this review can help to facilitate the interpretation of different diagnostic tests and raise awareness of their advantages and limitations. Additionally, diagnostic trees depict recommended diagnostic steps that should be performed in cats suspected of having FIP based on their clinical signs or clinicopathologic abnormalities. These steps can easily be followed in clinical practice.",2019 Nov 15,"['Felten, Sandra', 'Hartmann, Katrin']",Viruses,,,True
13ab857b7b076f5a00bb3becf27e9780fcecf26e,PMC,In-Vitro Subtype-Specific Modulation of HIV-1 Trans-Activator of Transcription (Tat) on RNAi Silencing Suppressor Activity and Cell Death,http://dx.doi.org/10.3390/v11110976,PMC6893708,31652847,CC BY,"Human immunodeficiency virus (HIV) is a global health concern affecting millions of individuals with a wide variety of currently circulating subtypes affecting various regions of the globe. HIV relies on multiple regulatory proteins to modify the host cell to promote replication in infected T cells, and these regulatory proteins can have subtle phenotypic differences between subtypes. One of these proteins, HIV-1 Trans-Activator of Transcription (Tat), is capable of RNA interference (RNAi) Silencing Suppressor (RSS) activity and induction of cell death in T cells. However, the subtype-specific RSS activity and induction of cell death have not been explored. We investigated the ability of Tat subtypes and variants to induce RSS activity and cell death. TatB, from HIV-1 subtype B, was found to be a potent RSS activator by 40% whereas TatC, from HIV-1 subtype C, showed 15% RSS activity while subtype TatC variants exhibited varying levels. A high level of cell death (50–53%) was induced by subtype TatB when compared to subtype TatC (25–28%) and varying levels were observed with subtype TatC variants. These differential activities could be due to variations in the functional domains of Tat. These observations further our understanding of subtype-specific augmentation of Tat in HIV-1 replication and pathogenesis.",2019 Oct 23,"['Ronsard, Larance', 'S. Yousif, Ashraf', 'Ramesh, Janani', 'Sumi, N.', 'Gorman, Matthew', 'G. Ramachandran, Vishnampettai', 'C. Banerjea, Akhil']",Viruses,,,True
05f1c02ecdb1798e85e750ddfa81ede861f94cf6,PMC,"The Rescue and Characterization of Recombinant, Microcephaly-Associated Zika Viruses as Single-Round Infectious Particles",http://dx.doi.org/10.3390/v11111005,PMC6893733,31683628,CC BY,"Zika virus (ZIKV) is transmitted by Aedes mosquitoes and exhibits genetic variation with African and Asian lineages. ZIKV Natal RGN strain, an Asian-lineage virus, has been identified in brain tissues from fetal autopsy cases with microcephaly and is suggested to be a neurotropic variant. However, ZIKV Natal RGN strain has not been isolated; its biological features are not yet illustrated. This study rescued and characterized recombinant, single-round infectious particles (SRIPs) of the ZIKV Natal RGN strain using reverse genetic and synthetic biology techniques. The DNA-launched replicon of ZIKV Natal RGN was constructed and contains the EGFP reporter, lacks prM-E genes, and replicates under CMV promoter control. The peak in the ZIKV Natal RGN SRIP titer reached 6.25 × 10(6) TCID50/mL in the supernatant of prM-E-expressing packaging cells 72 h post-transfection with a ZIKV Natal RGN replicon. The infectivity of ZIKV Natal RGN SRIPs has been demonstrated to correlate with the green florescence intensity of the EGFP reporter, the SRIP-induced cytopathic effect, and ZIKV’s non-structural protein expression. Moreover, ZIKV Natal RGN SRIPs effectively self-replicated in rhabdomyosarcoma/muscle, glioblastoma/astrocytoma, and retinal pigmented epithelial cells, displaying unique cell susceptibility with differential attachment activity. Therefore, the recombinant ZIKV Natal RGN strain was rescued as SRIPs that could be used to elucidate the biological features of a neurotropic strain regarding cell tropism and pathogenic components, apply for antiviral agent screening, and develop vaccine candidates.",2019 Oct 31,"['Lu, Chien-Yi', 'Lin, Chen-Sheng', 'Lai, Hsueh-Chou', 'Yu, Ya-Wen', 'Liao, Chih-Yi', 'Su, Wen-Chi', 'Ko, Bo-Han', 'Chang, Young-Sheng', 'Huang, Su-Hua', 'Lin, Cheng-Wen']",Viruses,,,True
9d343eb083c8716c946575e15df1688e58d0b288,PMC,"The Rescue and Characterization of Recombinant, Microcephaly-Associated Zika Viruses as Single-Round Infectious Particles",http://dx.doi.org/10.3390/v11111005,PMC6893733,31683628,CC BY,"Zika virus (ZIKV) is transmitted by Aedes mosquitoes and exhibits genetic variation with African and Asian lineages. ZIKV Natal RGN strain, an Asian-lineage virus, has been identified in brain tissues from fetal autopsy cases with microcephaly and is suggested to be a neurotropic variant. However, ZIKV Natal RGN strain has not been isolated; its biological features are not yet illustrated. This study rescued and characterized recombinant, single-round infectious particles (SRIPs) of the ZIKV Natal RGN strain using reverse genetic and synthetic biology techniques. The DNA-launched replicon of ZIKV Natal RGN was constructed and contains the EGFP reporter, lacks prM-E genes, and replicates under CMV promoter control. The peak in the ZIKV Natal RGN SRIP titer reached 6.25 × 10(6) TCID50/mL in the supernatant of prM-E-expressing packaging cells 72 h post-transfection with a ZIKV Natal RGN replicon. The infectivity of ZIKV Natal RGN SRIPs has been demonstrated to correlate with the green florescence intensity of the EGFP reporter, the SRIP-induced cytopathic effect, and ZIKV’s non-structural protein expression. Moreover, ZIKV Natal RGN SRIPs effectively self-replicated in rhabdomyosarcoma/muscle, glioblastoma/astrocytoma, and retinal pigmented epithelial cells, displaying unique cell susceptibility with differential attachment activity. Therefore, the recombinant ZIKV Natal RGN strain was rescued as SRIPs that could be used to elucidate the biological features of a neurotropic strain regarding cell tropism and pathogenic components, apply for antiviral agent screening, and develop vaccine candidates.",2019 Oct 31,"['Lu, Chien-Yi', 'Lin, Chen-Sheng', 'Lai, Hsueh-Chou', 'Yu, Ya-Wen', 'Liao, Chih-Yi', 'Su, Wen-Chi', 'Ko, Bo-Han', 'Chang, Young-Sheng', 'Huang, Su-Hua', 'Lin, Cheng-Wen']",Viruses,,,False
3d758d41ef57c3d1e9ffe346ece0dd6b59e68cd8,PMC,Parechovirus A Pathogenesis and the Enigma of Genotype A-3,http://dx.doi.org/10.3390/v11111062,PMC6893760,31739613,CC BY,"Parechovirus A is a species in the Parechovirus genus within the Picornaviridae family that can cause severe disease in children. Relatively little is known on Parechovirus A epidemiology and pathogenesis. This review aims to explore the Parechovirus A literature and highlight the differences between Parechovirus A genotypes from a pathogenesis standpoint. In particular, the curious case of Parechovirus-A3 and the genotype-specific disease association will be discussed. Finally, a brief outlook on Parechovirus A research is provided.",2019 Nov 14,"['Sridhar, Adithya', 'Karelehto, Eveliina', 'Brouwer, Lieke', 'Pajkrt, Dasja', 'Wolthers, Katja C.']",Viruses,,,True
3f2d44465b679efa6237f96e001dcf8a9e9bd6ff,PMC,Zika Virus Non-Structural Protein NS5 Inhibits the RIG-I Pathway and Interferon Lambda 1 Promoter Activation by Targeting IKK Epsilon,http://dx.doi.org/10.3390/v11111024,PMC6893776,31690057,CC BY,"The Zika virus (ZIKV) is a member of the Flaviviridae family and an important human pathogen. Most pathogenic viruses encode proteins that interfere with the activation of host innate immune responses. Like other flaviviruses, ZIKV interferes with the expression of interferon (IFN) genes and inhibits IFN-induced antiviral responses. ZIKV infects through epithelial barriers where IFN-λ1 is an important antiviral molecule. In this study, we analyzed the effects of ZIKV proteins on the activation of IFN-λ1 promoter. All ZIKV proteins were cloned and transiently expressed. ZIKV NS5, but no other ZIKV protein, was able to interfere with the RIG-I signaling pathway. This inhibition took place upstream of interferon regulatory factor 3 (IRF3) resulting in reduced phosphorylation of IRF3 and reduced activation of IFN-λ1 promoter. Furthermore, we showed that ZIKV NS5 interacts with the protein kinase IKKε, which is likely critical to the observed inhibition of phosphorylation of IRF3.",2019 Nov 4,"['Lundberg, Rickard', 'Melén, Krister', 'Westenius, Veera', 'Jiang, Miao', 'Österlund, Pamela', 'Khan, Hira', 'Vapalahti, Olli', 'Julkunen, Ilkka', 'Kakkola, Laura']",Viruses,,,True
9764af198bccd196d117b460ad8112059b4f6b00,PMC,Pan-European Study on the Prevalence of the Feline Leukaemia Virus Infection – Reported by the European Advisory Board on Cat Diseases (ABCD Europe),http://dx.doi.org/10.3390/v11110993,PMC6893802,31671816,CC BY,"Feline leukaemia virus (FeLV) is a retrovirus associated with fatal disease in progressively infected cats. While testing/removal and vaccination led to a decreased prevalence of FeLV, recently, this decrease has reportedly stagnated in some countries. This study aimed to prospectively determine the prevalence of FeLV viraemia in cats taken to veterinary facilities in 32 European countries. FeLV viral RNA was semiquantitatively detected in saliva, using RT-qPCR as a measure of viraemia. Risk and protective factors were assessed using an online questionnaire to report geographic, demographic, husbandry, FeLV vaccination, and clinical data. The overall prevalence of FeLV viraemia in cats visiting a veterinary facility, of which 10.4% were shelter and rescue cats, was 2.3% (141/6005; 95% CI: 2.0%–2.8%) with the highest prevalences in Portugal, Hungary, and Italy/Malta (5.7%–8.8%). Using multivariate analysis, seven risk factors (Southern Europe, male intact, 1–6 years of age, indoor and outdoor or outdoor-only living, living in a group of ≥5 cats, illness), and three protective factors (Northern Europe, Western Europe, pedigree cats) were identified. Using classification and regression tree (CART) analysis, the origin of cats in Europe, pedigree, and access to outdoors were important predictors of FeLV status. FeLV-infected sick cats shed more viral RNA than FeLV-infected healthy cats, and they suffered more frequently from anaemia, anorexia, and gingivitis/stomatitis than uninfected sick cats. Most cats had never been FeLV-vaccinated; vaccination rates were indirectly associated with the gross domestic product (GDP) per capita. In conclusion, we identified countries where FeLV was undetectable, demonstrating that the infection can be eradicated and highlighting those regions where awareness and prevention should be increased.",2019 Oct 29,"['Studer, Nadine', 'Lutz, Hans', 'Saegerman, Claude', 'Gönczi, Enikö', 'Meli, Marina L.', 'Boo, Gianluca', 'Hartmann, Katrin', 'Hosie, Margaret J.', 'Moestl, Karin', 'Tasker, Séverine', 'Belák, Sándor', 'Lloret, Albert', 'Boucraut-Baralon, Corine', 'Egberink, Herman F.', 'Pennisi, Maria-Grazia', 'Truyen, Uwe', 'Frymus, Tadeusz', 'Thiry, Etienne', 'Marsilio, Fulvio', 'Addie, Diane', 'Hochleithner, Manfred', 'Tkalec, Filip', 'Vizi, Zsuzsanna', 'Brunetti, Anna', 'Georgiev, Boyko', 'Ludwig-Begall, Louisa F.', 'Tschuor, Flurin', 'Mooney, Carmel T.', 'Eliasson, Catarina', 'Orro, Janne', 'Johansen, Helle', 'Juuti, Kirsi', 'Krampl, Igor', 'Kovalenko, Kaspars', 'Šengaut, Jakov', 'Sobral, Cristina', 'Borska, Petra', 'Kovaříková, Simona', 'Hofmann-Lehmann, Regina']",Viruses,,,True
9633dd466a1f1c402c18d7db00bae7bf1eea5250,PMC,Clinical and epidemiological characteristics of imported dengue fever among inbound passengers: Infrared thermometer–based active surveillance at an international airport,http://dx.doi.org/10.1371/journal.pone.0225840,PMC6894787,31805101,CC BY,"BACKGROUND: Dengue fever is endemic in tropical and subtropical areas, especially Southeast Asia. International air travel facilitates the spread of dengue across and within borders. To date, no predictive factors have been established for assessing risk of dengue among febrile travelers. METHODS: Since 2006, Taiwan has operated a program of infrared thermometer–based non-contact active surveillance at Taoyuan International Airport (TPE). All inbound passengers from dengue-endemic countries who are febrile (tympanic temperature ≥38°C) undergo routine laboratory testing for dengue. We analyzed clinical and epidemiological characteristics of all tested passengers entering Taiwan via TPE in 2011 to identify the predictive factors of dengue infection. RESULTS: In 2011, of the 3,719 febrile passengers from dengue-endemic countries, 74 (2.0%) had laboratory-confirmed dengue infection. Multivariable logistic regression analysis revealed that those who were aged ≥60 years (adjusted odds ratio [aOR], 8.7; 95% confidence interval [CI], 2.6–29.6) and had self-reported fever (aOR, 2.5; 95% CI, 1.5–4.1), skin rashes (aOR, 11.0; 95% CI, 3.4–35.1), or a tympanic temperature ≥39°C (aOR, 2.9; 95% CI, 1.7–4.9) were significantly more likely to have dengue (all p values < 0.05). Compared with travelers who stayed in dengue-endemic countries for ≤7 days, those who traveled 8–14, 15–21, 22–28, and ≥29 days were also more likely to be infected (aORs of 10.2, 14.9, 39.0 and 12.0, respectively). CONCLUSION: These clinical and epidemiological features can facilitate timely recognition and diagnosis of imported dengue in febrile inbound passengers and therefore help prevent domestic transmission of dengue virus.",2019 Dec 5,"['Su, Chia-ping', 'Wang, Ying-Yun', 'Ku, Kuei-Chu', 'Fang, Chi-Tai']",PLoS One,,,True
06753b3e708ad76787b100b9009ccec622f267ae,PMC,Emodin Inhibits EBV Reactivation and Represses NPC Tumorigenesis,http://dx.doi.org/10.3390/cancers11111795,PMC6896023,31731581,CC BY,"Nasopharyngeal carcinoma (NPC) is a unique malignancy derived from the epithelium of the nasopharynx. Despite great advances in the development of radiotherapy and chemotherapy, relapse and metastasis in NPC patients remain major causes of mortality. Evidence accumulated over recent years indicates that Epstein-Barr virus (EBV) lytic replication plays an important role in the pathogenesis of NPC and inhibition of EBV reactivation is now being considered as a goal for the therapy of EBV-associated cancers. With this in mind, a panel of dietary compounds was screened and emodin was found to have potential anti-EBV activity. Through Western blotting, immunofluorescence, and flow cytometric analysis, we show that emodin inhibits the expression of EBV lytic proteins and blocks virion production in EBV- positive epithelial cell lines. In investigating the underlying mechanism, reporter assays indicated that emodin represses Zta promoter (Zp) and Rta promoter (Rp) activities, triggered by various inducers. Mapping of the Zp construct reveals that the SP1 binding region is important for emodin-triggered repression and emodin is shown to be able to inhibit SP1 expression, suggesting that it likely inhibits EBV reactivation by suppression of SP1 expression. Moreover, we also show that emodin inhibits the tumorigenic properties induced by repeated EBV reactivation, including micronucleus formation, cell proliferation, migration, and matrigel invasiveness. Emodin administration also represses the tumor growth in mice which is induced by EBV activation. Taken together, our results provide a potential chemopreventive agent in restricting EBV reactivation and NPC recurrence.",2019 Nov 15,"['Wu, Chung-Chun', 'Chen, Mei-Shu', 'Cheng, Yu-Jhen', 'Ko, Ying-Chieh', 'Lin, Su-Fang', 'Chiu, Ing-Ming', 'Chen, Jen-Yang']",Cancers (Basel),,,True
c7c5ce7b19ccf87effd293c9ef58e343835b4728,PMC,Emodin Inhibits EBV Reactivation and Represses NPC Tumorigenesis,http://dx.doi.org/10.3390/cancers11111795,PMC6896023,31731581,CC BY,"Nasopharyngeal carcinoma (NPC) is a unique malignancy derived from the epithelium of the nasopharynx. Despite great advances in the development of radiotherapy and chemotherapy, relapse and metastasis in NPC patients remain major causes of mortality. Evidence accumulated over recent years indicates that Epstein-Barr virus (EBV) lytic replication plays an important role in the pathogenesis of NPC and inhibition of EBV reactivation is now being considered as a goal for the therapy of EBV-associated cancers. With this in mind, a panel of dietary compounds was screened and emodin was found to have potential anti-EBV activity. Through Western blotting, immunofluorescence, and flow cytometric analysis, we show that emodin inhibits the expression of EBV lytic proteins and blocks virion production in EBV- positive epithelial cell lines. In investigating the underlying mechanism, reporter assays indicated that emodin represses Zta promoter (Zp) and Rta promoter (Rp) activities, triggered by various inducers. Mapping of the Zp construct reveals that the SP1 binding region is important for emodin-triggered repression and emodin is shown to be able to inhibit SP1 expression, suggesting that it likely inhibits EBV reactivation by suppression of SP1 expression. Moreover, we also show that emodin inhibits the tumorigenic properties induced by repeated EBV reactivation, including micronucleus formation, cell proliferation, migration, and matrigel invasiveness. Emodin administration also represses the tumor growth in mice which is induced by EBV activation. Taken together, our results provide a potential chemopreventive agent in restricting EBV reactivation and NPC recurrence.",2019 Nov 15,"['Wu, Chung-Chun', 'Chen, Mei-Shu', 'Cheng, Yu-Jhen', 'Ko, Ying-Chieh', 'Lin, Su-Fang', 'Chiu, Ing-Ming', 'Chen, Jen-Yang']",Cancers (Basel),,,False
11914635e8fc7c041e815263d5e20ca4ad9166bb,PMC,Evaluation of bacteriophage efficacy in reducing the impact of single and mixed infections with Escherichia coli and infectious bronchitis in chickens,http://dx.doi.org/10.1080/20008686.2019.1686822,PMC6896464,31839902,CC BY,"Infectious bronchitis virus (IBV) represents a major threat to poultry production worldwide particularly when complicated with bacterial infection. In the present study samples were collected from forty broiler farms with respiratory manifestations to characterize IBV and E. coli. Bacteriophages were isolated and enriched from sampled farms to study its efficacy to control single and mixed infections with E. coli and IBV in vivo. Twelve out of forty farms were positive for IBV. Phylogenetic analysis of partial spike protein revealed that all positive cases clustered within the GI-23 genotype. Eight out of forty farms were positive for E. coli serogroups O26, O78, O86, O114, O119, with O125 found on three farms. Bacteriophage treatment delayed the onset and reduced the severity of clinical signs, and prevented the mortality associated with single and mixed infection with IBV and E. coli. Furthermore, in mixed infections, bacteriophage treatment significantly reduced E. coli as well as IBV shedding. Groups treated with bacteriophages showed a significant reduction of E. coli shedding that gradually decreased over time, in contrast to higher and gradually increasing shedding without bacteriophage treatment. In conclusion, bacteriophage treatment significantly reduced the pathogenicity and shedding of IBVand E. coli in mixed infections.",2019 Nov 29,"['Tawakol, Maram M.', 'Nabil, Nehal M.', 'Samy, Ahmed']",Infect Ecol Epidemiol,,,True
b9fb16bb3df1fc1af7dd479e06c120f376362880,PMC,High levels of unreported intraspecific diversity among RNA viruses in faeces of neonatal piglets with diarrhoea,http://dx.doi.org/10.1186/s12917-019-2204-2,PMC6896758,31805938,CC BY,"BACKGROUND: Diarrhoea is a major cause of death in neonate pigs and most of the viruses that cause it are RNA viruses. Next Generation Sequencing (NGS) deeply characterize the genetic diversity among rapidly mutating virus populations at the interspecific as well as the intraspecific level. The diversity of RNA viruses present in faeces of neonatal piglets suffering from diarrhoea in 47 farms, plus 4 samples from non-diarrhoeic piglets has been evaluated by NGS. Samples were selected among the cases submitted to the Veterinary Diagnostic Laboratories of Infectious Diseases of the Universitat Autònoma de Barcelona (Barcelona, Spain) and Universidad de León (León, Spain). RESULTS: The analyses identified the presence of 12 virus species corresponding to 8 genera of RNA viruses. Most samples were co-infected by several viruses. Kobuvirus and Rotavirus were more commonly reported, with Sapovirus, Astrovirus 3, 4 and 5, Enterovirus G, Porcine epidemic diarrhoea virus, Pasivirus and Posavirus being less frequently detected. Most sequences showed a low identity with the sequences deposited in GenBank, allowing us to propose several new VP4 and VP7 genotypes for Rotavirus B and Rotavirus C. CONCLUSIONS: Among the cases analysed, Rotaviruses were the main aetiological agents of diarrhoea in neonate pigs. Besides, in a small number of cases Kobuvirus and Sapovirus may also have an aetiological role. Even most animals were co-infected in early life, the association with enteric disease among the other examined viruses was unclear. The NGS method applied successfully characterized the RNA virome present in faeces and detected a high level of unreported intraspecific diversity.",2019 Dec 5,"['Cortey, Martí', 'Díaz, Ivan', 'Vidal, Anna', 'Martín-Valls, Gerard', 'Franzo, Giovanni', 'Gómez de Nova, Pedro José', 'Darwich, Laila', 'Puente, Héctor', 'Carvajal, Ana', 'Martín, Marga', 'Mateu, Enric']",BMC Vet Res,,,True
1d8d4fed8118f54a4a5db8892cc5e5bbbf19afa4,PMC,Improvement in Clinical Symptoms and Fecal Microbiome After Fecal Microbiota Transplantation in a Dog with Inflammatory Bowel Disease,http://dx.doi.org/10.2147/VMRR.S230862,PMC6898721,31819862,CC BY,"PURPOSE: Recently, fecal microbiota transplantation (FMT) has been tested in veterinary medicine as a treatment option for multiple gastrointestinal (GI) diseases, such as inflammatory bowel disease (IBD). However, there are no reports of changes in the microbial diversity of fecal microbiome after treatment with FMT in canine IBD cases. Moreover, little is known about the long-term efficacy and safety of FMT treatment for dogs. Herein, we present a case of canine intractable IBD treated with repeated, long-term FMT. PATIENTS AND METHODS: The patient was a 10-year-old, neutered, male, 4-kg Toy Poodle with a prolonged history of vomiting and diarrhea. Fecal examination for pathogens was negative. Despite treatment with multiple antibacterial and antidiarrheal agents, the patient showed no improvement. Endoscopic mucus sampling diagnosed a case of lymphocytic-plasmacytic duodenitis, ie, idiopathic IBD. Eventually, we performed periodic, long-term fecal microbiota transplantation of fresh donor feces collected from a 4-year-old, 32.8-kg, neutered male Golden Retriever by rectal enema. Additionally, we performed 16S rRNA sequence analysis, before and after FMT, to evaluate the microbiome diversity. RESULTS: Fecal microbiome diversity after FMT resembled that of the healthy donor dog’s fecal microbiome, before FMT, which led us to conclude that the fecal microbiome in our patient normalized with FMT. Moreover, the clinical symptoms improved remarkably with regard to the changes in the fecal microbiome. Additionally, we noted no observable side effects during FMT treatment. CONCLUSION: This report indicates the efficacy and safety of long-term, periodic FMT for a case of canine IBD based on attenuation of clinical symptoms and changes in fecal microbiome diversity. Therefore, FMT could be chosen as a treatment option for IBD in canines in the future.",2019 Dec 2,"['Niina, Ayaka', 'Kibe, Ryoko', 'Suzuki, Ryohei', 'Yuchi, Yunosuke', 'Teshima, Takahiro', 'Matsumoto, Hirotaka', 'Kataoka, Yasushi', 'Koyama, Hidekazu']",Vet Med (Auckl),,,True
1cc16427f0accab0051485dbbb73dbce1d0848e4,PMC,A systematic review of MERS-CoV seroprevalence and RNA prevalence in dromedary camels: Implications for animal vaccination,http://dx.doi.org/10.1016/j.epidem.2019.100350,PMC6899506,31201040,CC BY,"Human infection with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is driven by recurring dromedary-to-human spill-over events, leading decision-makers to consider dromedary vaccination. Dromedary vaccine candidates in the development pipeline are showing hopeful results, but gaps in our understanding of the epidemiology of MERS-CoV in dromedaries must be addressed to design and evaluate potential vaccination strategies. We aim to bring together existing measures of MERS-CoV infection in dromedary camels to assess the distribution of infection, highlighting knowledge gaps and implications for animal vaccination. We systematically reviewed the published literature on MEDLINE, EMBASE and Web of Science that reported seroprevalence and/or prevalence of active MERS-CoV infection in dromedary camels from both cross-sectional and longitudinal studies. 60 studies met our eligibility criteria. Qualitative syntheses determined that MERS-CoV seroprevalence increased with age up to 80–100% in adult dromedaries supporting geographically widespread endemicity of MERS-CoV in dromedaries in both the Arabian Peninsula and countries exporting dromedaries from Africa. The high prevalence of active infection measured in juveniles and at sites where dromedary populations mix should guide further investigation – particularly of dromedary movement – and inform vaccination strategy design and evaluation through mathematical modelling.",2019 Dec,"['Dighe, Amy', 'Jombart, Thibaut', 'Van Kerkhove, Maria D.', 'Ferguson, Neil']",Epidemics,,,False
8b264d2d749532dff506b14356b606029bb94035,PMC,Poultry trading behaviours in Vietnamese live bird markets as risk factors for avian influenza infection in chickens,http://dx.doi.org/10.1111/tbed.13308,PMC6899644,31357255,CC BY,"Vietnamese poultry are host to co‐circulating subtypes of avian influenza viruses, including H5N1 and H9N2, which pose a great risk to poultry productivity and to human health. AIVs circulate throughout the poultry trade network in Vietnam, with live bird markets being an integral component to this network. Traders at LBMs exhibit a variety of trading practices, which may influence the transmission of AIVs. We identified trading practices that impacted on AIV prevalence in chickens marketed in northern Vietnamese LBMs. We generated sequencing data for 31 H9N2 and two H5N6 viruses. Viruses isolated in the same LBM or from chickens sourced from the same province were genetically closer than viruses isolated in different LBMs or from chickens sourced in different provinces. The position of a vendor in the trading network impacted on their odds of having AIV‐infected chickens. Being a retailer and purchasing chickens from middlemen was associated with increased odds of infection, whereas odds decreased if vendors purchased chickens directly from large farms. Odds of infection were also higher for vendors having a greater volume of ducks unsold per day. These results indicate how the spread of AIVs is influenced by the structure of the live poultry trading network.",2019 Nov 9,"['Sealy, Joshua E.', 'Fournie, Guillaume', 'Trang, Pham Hong', 'Dang, Nguyen Hoang', 'Sadeyen, Jean‐Remy', 'Thanh, To Long', 'van Doorn, H. Rogier', 'Bryant, Juliet E.', 'Iqbal, Munir']",Transbound Emerg Dis,,,True
6f9149e2caa1229df655448839a15cafab5a03e0,PMC,Old World camels in a modern world – a balancing act between conservation and genetic improvement,http://dx.doi.org/10.1111/age.12858,PMC6899786,31532019,CC BY,"Old World camels have served humans in cross‐continental caravans, transporting people and goods, connecting different cultures and providing milk, meat, wool and draught since their domestication around 3000–6000 years ago. In a world of modern transport and fast connectivity, these beasts of burden seem to be out‐dated. However, a growing demand for sustainable milk and meat production, especially in countries affected by climate change and increasing desertification, brings dromedaries (Camelus dromedarius) and Bactrian camels (Camelus bactrianus) back onstage and into the focus of animal breeders and scientists. In this review on the molecular genetics of these economically important species we give an overview about the evolutionary history, domestication and dispersal of Old World camels, whereas highlighting the need for conservation of wild two‐humped camels (Camelus ferus) as an evolutionarily unique and highly endangered species. We provide cutting‐edge information on the current molecular resources and on‐going sequencing projects. We cannot emphasise enough the importance of balancing the need for improving camel production traits with maintaining the genetic diversity in two domestic species with specific physiological adaptation to a desert environment.",2019 Dec 18,"['Burger, P. A.', 'Ciani, E.', 'Faye, B.']",Anim Genet,,,True
d10f84b9e2232aef0a3d90771b3f861208456d2d,PMC,"The Emerging Role of Rhinoviruses in Lower Respiratory Tract Infections in Children – Clinical and Molecular Epidemiological Study From Croatia, 2017–2019",http://dx.doi.org/10.3389/fmicb.2019.02737,PMC6901631,31849887,CC BY,"Rhinoviruses (RVs) are increasingly implicated not only in mild upper respiratory tract infections, but also in more severe lower respiratory tract infections; however, little is known about species diversity and viral epidemiology of RVs among the infected children. Therefore, we investigated the rhinovirus (RV) infection prevalence over a 2-year period, compared it with prevalence patterns of other common respiratory viruses, and explored clinical and molecular epidemiology of RV infections among 590 children hospitalized with acute respiratory infection in north-western and central parts of Croatia. For respiratory virus detection, nasopharyngeal and pharyngeal flocked swabs were taken from each patient and subsequently analyzed with multiplex RT-PCR. To determine the RV species in a subset of positive children, 5′UTR in RV-positive samples has been sequenced. Nucleotide sequences of referent RV strains were retrieved by searching the database with Basic Local Alignment Tool, and used to construct alignments and phylogenetic trees using MAFFT multiple sequence alignment tool and the maximum likelihood method, respectively. In our study population RV was the most frequently detected virus, diagnosed in 197 patients (33.4%), of which 60.4% was detected as a monoinfection. Median age of RV-infected children was 2.25 years, and more than half of children infected with RV (55.8%) presented with lower respiratory tract infections. Most RV cases were detected from September to December, and all three species co-circulated during the analyzed period (2017–2019). Sequence analysis based on 5′UTR region yielded 69 distinct strains; the most prevalent was RV-C (47.4%) followed by RV-A (44.7%) and RV-B (7.9%). Most of RV-A sequences formed a distinct phylogenetic group; only strains RI/HR409-18 (along with a reference strain MF978777) clustered with RV-C strains. Strains belonging to the group C were the most diverse (41.6% identity among strains), while group B was the most conserved (71.5% identity among strains). Despite such differences in strain groups (hitherto undescribed in Croatia), clinical presentation of infected children was rather similar. Our results are consistent with newer studies that investigated the etiology of acute respiratory infections, especially those focused on children with lower respiratory tract infections, where RVs should always be considered as potentially serious pathogens.",2019 Dec 3,"['Ljubin-Sternak, Sunčanica', 'Meštrović, Tomislav', 'Ivković-Jureković, Irena', 'Kolarić, Branko', 'Slović, Anamarija', 'Forčić, Dubravko', 'Tot, Tatjana', 'Mijač, Maja', 'Vraneš, Jasmina']",Front Microbiol,,,True
475d4a59b08bc0524da46806dae55989e57dac4e,PMC,Clinical Features Predicting Mortality Risk in Patients With Viral Pneumonia: The MuLBSTA Score,http://dx.doi.org/10.3389/fmicb.2019.02752,PMC6901688,31849894,CC BY,"OBJECTIVE: The aim of this study was to further clarify clinical characteristics and predict mortality risk among patients with viral pneumonia. METHODS: A total of 528 patients with viral pneumonia at RuiJin hospital in Shanghai from May 2015 to May 2019 were recruited. Multiplex real-time RT-PCR was used to detect respiratory viruses. Demographic information, comorbidities, routine laboratory examinations, immunological indexes, etiological detections, radiological images and treatment were collected on admission. RESULTS: 76 (14.4%) patients died within 90 days in hospital. A predictive MuLBSTA score was calculated on the basis of a multivariate logistic regression model in order to predict mortality with a weighted score that included multilobular infiltrates (OR = 5.20, 95% CI 1.41–12.52, p = 0.010; 5 points), lymphocyte ≤ 0.8(∗)10(9)/L (OR = 4.53, 95% CI 2.55–8.05, p < 0.001; 4 points), bacterial coinfection (OR = 3.71, 95% CI 2.11–6.51, p < 0.001; 4 points), acute-smoker (OR = 3.19, 95% CI 1.34–6.26, p = 0.001; 3 points), quit-smoker (OR = 2.18, 95% CI 0.99–4.82, p = 0.054; 2 points), hypertension (OR = 2.39, 95% CI 1.55–4.26, p = 0.003; 2 points) and age ≥60 years (OR = 2.14, 95% CI 1.04–4.39, p = 0.038; 2 points). 12 points was used as a cut-off value for mortality risk stratification. This model showed sensitivity of 0.776, specificity of 0.778 and a better predictive ability than CURB-65 (AUROC = 0.773 vs. 0.717, p < 0.001). CONCLUSION: Here, we designed an easy-to-use clinically predictive tool for assessing 90-day mortality risk of viral pneumonia. It can accurately stratify hospitalized patients with viral pneumonia into relevant risk categories and could provide guidance to make further clinical decisions.",2019 Dec 3,"['Guo, Lingxi', 'Wei, Dong', 'Zhang, Xinxin', 'Wu, Yurong', 'Li, Qingyun', 'Zhou, Min', 'Qu, Jieming']",Front Microbiol,,,True
7f85b3d05b0140dcee8a2d7e75603ddda63dcd2e,PMC,Zebrafish TRIM25 Promotes Innate Immune Response to RGNNV Infection by Targeting 2CARD and RD Regions of RIG-I for K63-Linked Ubiquitination,http://dx.doi.org/10.3389/fimmu.2019.02805,PMC6901795,31849979,CC BY,"RIG-I-like receptors (RLRs) play important roles in response to virus infection by regulating host innate immune signaling pathways. Meanwhile, the RLR signaling pathway is also tightly regulated by host and virus to achieve the immune homeostasis between antiviral responses and virus survival. Here, we found that zebrafish TRIM25 (zbTRIM25) functioned as a positive regulator of RLR signaling pathway during red spotted grouper nervous necrosis virus (RGNNV) infection. Post-RGNNV infection, zbTRIM25 expression was obviously inhibited and ectopic expression of zbTRIM25 led to enhanced expression of RLR signaling pathway-related genes. Overexpression and knockdown analysis revealed that zbTRIM25 promoted zebrafish RIG-I (zbRIG-I)-mediated IFN signaling and inhibited RGNNV replication. Mechanistically, zbTRIM25 bound to zbRIG-I; in particular, the SPRY domain of zbTRIM25 interacted with the tandem caspase activation and recruitment domains (2CARD) and repressor domain (RD) regions of zbRIG-I. zbTRIM25 promoted the K63 polyubiquitination of 2CARD and RD regions of zbRIG-I. Furthermore, zbTRIM25-mediated zbRIG-I activation of IFN production was enhanced by K63-linked ubiquitin, indicating that zbTRIM25-mediated zbRIG-I polyubiquitination was essential for RIG-I-triggered IFN induction. In conclusion, these findings reveal a novel mechanism that zbTRIM25 positively regulates the innate immune response by targeting and promoting the K63-linked polyubiquitination of zbRIG-I.",2019 Dec 3,"['Jin, Yilin', 'Jia, Kuntong', 'Zhang, Wanwan', 'Xiang, Yangxi', 'Jia, Peng', 'Liu, Wei', 'Yi, Meisheng']",Front Immunol,,,False
9a87a6bf36af7342e6bbb2e13da6181a8c0bab27,PMC,Zebrafish TRIM25 Promotes Innate Immune Response to RGNNV Infection by Targeting 2CARD and RD Regions of RIG-I for K63-Linked Ubiquitination,http://dx.doi.org/10.3389/fimmu.2019.02805,PMC6901795,31849979,CC BY,"RIG-I-like receptors (RLRs) play important roles in response to virus infection by regulating host innate immune signaling pathways. Meanwhile, the RLR signaling pathway is also tightly regulated by host and virus to achieve the immune homeostasis between antiviral responses and virus survival. Here, we found that zebrafish TRIM25 (zbTRIM25) functioned as a positive regulator of RLR signaling pathway during red spotted grouper nervous necrosis virus (RGNNV) infection. Post-RGNNV infection, zbTRIM25 expression was obviously inhibited and ectopic expression of zbTRIM25 led to enhanced expression of RLR signaling pathway-related genes. Overexpression and knockdown analysis revealed that zbTRIM25 promoted zebrafish RIG-I (zbRIG-I)-mediated IFN signaling and inhibited RGNNV replication. Mechanistically, zbTRIM25 bound to zbRIG-I; in particular, the SPRY domain of zbTRIM25 interacted with the tandem caspase activation and recruitment domains (2CARD) and repressor domain (RD) regions of zbRIG-I. zbTRIM25 promoted the K63 polyubiquitination of 2CARD and RD regions of zbRIG-I. Furthermore, zbTRIM25-mediated zbRIG-I activation of IFN production was enhanced by K63-linked ubiquitin, indicating that zbTRIM25-mediated zbRIG-I polyubiquitination was essential for RIG-I-triggered IFN induction. In conclusion, these findings reveal a novel mechanism that zbTRIM25 positively regulates the innate immune response by targeting and promoting the K63-linked polyubiquitination of zbRIG-I.",2019 Dec 3,"['Jin, Yilin', 'Jia, Kuntong', 'Zhang, Wanwan', 'Xiang, Yangxi', 'Jia, Peng', 'Liu, Wei', 'Yi, Meisheng']",Front Immunol,,,True
2aa31ef3d9d80509a965846122911a3fc53f7a99,PMC,Biological Activities of Secretory RNases: Focus on Their Oligomerization to Design Antitumor Drugs,http://dx.doi.org/10.3389/fimmu.2019.02626,PMC6901985,31849926,CC BY,"Ribonucleases (RNases) are a large number of enzymes gathered into different bacterial or eukaryotic superfamilies. Bovine pancreatic RNase A, bovine seminal BS-RNase, human pancreatic RNase 1, angiogenin (RNase 5), and amphibian onconase belong to the pancreatic type superfamily, while binase and barnase are in the bacterial RNase N1/T1 family. In physiological conditions, most RNases secreted in the extracellular space counteract the undesired effects of extracellular RNAs and become protective against infections. Instead, if they enter the cell, RNases can digest intracellular RNAs, becoming cytotoxic and having advantageous effects against malignant cells. Their biological activities have been investigated either in vitro, toward a number of different cancer cell lines, or in some cases in vivo to test their potential therapeutic use. However, immunogenicity or other undesired effects have sometimes been associated with their action. Nevertheless, the use of RNases in therapy remains an appealing strategy against some still incurable tumors, such as mesothelioma, melanoma, or pancreatic cancer. The RNase inhibitor (RI) present inside almost all cells is the most efficacious sentry to counteract the ribonucleolytic action against intracellular RNAs because it forms a tight, irreversible and enzymatically inactive complex with many monomeric RNases. Therefore, dimerization or multimerization could represent a useful strategy for RNases to exert a remarkable cytotoxic activity by evading the interaction with RI by steric hindrance. Indeed, the majority of the mentioned RNases can hetero-dimerize with antibody derivatives, or even homo-dimerize or multimerize, spontaneously or artificially. This can occur through weak interactions or upon introducing covalent bonds. Immuno-RNases, in particular, are fusion proteins representing promising drugs by combining high target specificity with easy delivery in tumors. The results concerning the biological features of many RNases reported in the literature are described and discussed in this review. Furthermore, the activities displayed by some RNases forming oligomeric complexes, the mechanisms driving toward these supramolecular structures, and the biological rebounds connected are analyzed. These aspects are offered with the perspective to suggest possible efficacious therapeutic applications for RNases oligomeric derivatives that could contemporarily lack, or strongly reduce, immunogenicity and other undesired side-effects.",2019 Nov 26,"['Gotte, Giovanni', 'Menegazzi, Marta']",Front Immunol,,,True
367aa0244a4b97d04590b92ba9dba13fccd07ce3,PMC,"Evaluation of the influenza sentinel surveillance system in the Democratic Republic of Congo, 2012–2015",http://dx.doi.org/10.1186/s12889-019-8008-2,PMC6902419,31823763,CC BY,"BACKGROUND: The World Health Organization recommends periodic evaluations of influenza surveillance systems to identify areas for improvement and provide evidence of data reliability for policymaking. However, data about the performance of established influenza surveillance systems are limited in Africa, including in the Democratic Republic of Congo (DRC). METHODS: We used the Centers for Disease Control and Prevention guidelines to evaluate the performance of the influenza sentinel surveillance system (ISSS) in DRC during 2012–2015. The performance of the system was evaluated using eight surveillance attributes: (i) data quality and completeness for key variables, (ii) timeliness, (iii) representativeness, (iv) flexibility, (v) simplicity, (vi) acceptability, (vii) stability and (viii) utility. For each attribute, specific indicators were developed and described using quantitative and qualitative methods. Scores for each indicator were as follows: < 60% weak performance; 60–79% moderate performance; ≥80% good performance. RESULTS: During 2012–2015, we enrolled and tested 4339 patients with influenza-like illness (ILI) and 2869 patients with severe acute respiratory illness (SARI) from 11 sentinel sites situated in 5 of 11 provinces. Influenza viruses were detected in 446 (10.3%) samples from patients with ILI and in 151 (5.5%) samples from patients with SARI with higher detection during December–May. Data quality and completeness was > 90% for all evaluated indicators. Other strengths of the system were timeliness, simplicity, stability and utility that scored > 70% each. Representativeness, flexibility and acceptability had moderate performance. It was reported that the ISSS contributed to: (i) a better understanding of the epidemiology, circulating patterns and proportional contribution of influenza virus among patients with ILI or SARI; (ii) acquisition of new key competences related to influenza surveillance and diagnosis; and (iii) continuous education of surveillance staff and clinicians at sentinel sites about influenza. However, due to limited resources no actions were undertaken to mitigate the impact of seasonal influenza epidemics. CONCLUSIONS: The system performed overall satisfactorily and provided reliable and timely data about influenza circulation in DRC. The simplicity of the system contributed to its stability. A better use of the available data could be made to inform and promote prevention interventions especially among the most vulnerable groups.",2019 Dec 10,"['Babakazo, Pélagie', 'Kabamba-Tshilobo, Joelle', 'Wemakoy, Emile Okitolonda', 'Lubula, Léopold', 'Manya, Léonie Kitoko', 'Ilunga, Benoit Kebela', 'Disasuani, Wally', 'Nkwembe, Edith', 'Kavunga-Membo, Hugo', 'Changachanga, Jean-Claude', 'Muhemedi, Saleh', 'Tamfum, Jean-Jacques Muyembe', 'Tempia, Stefano']",BMC Public Health,,,True
9d7be8a36427c181f25d57999d889ac99807ece3,PMC,Influenza virus detection: driving change in public health laboratories in the Western Pacific Region,http://dx.doi.org/10.5365/wpsar.2018.9.5.006,PMC6902649,31832255,CC BY,,2018 Sep 5,"['Squires, Raynal C', 'Reading, Patrick C', 'Sullivan, Sheena G', 'Barr, Ian G', 'Konings, Frank']",Western Pac Surveill Response J,,,True
71d8abeec95c4d64d23aebfb95379158d85253e3,PMC,Learning from recent outbreaks to strengthen risk communication capacity for the next influenza pandemic in the Western Pacific Region,http://dx.doi.org/10.5365/wpsar.2018.9.5.013,PMC6902657,31832249,CC BY,,2019 Feb 19,"['O’Connor, Lauren J', 'Peters, Lisa', 'Aynsley, Rose']",Western Pac Surveill Response J,,,True
d933299806fcd4e9e8a61e7760267154926c05ee,PMC,"Timeliness of infectious disease reporting, the Netherlands, 2003 to 2017: law change reduced reporting delay, disease identification delay is next",http://dx.doi.org/10.2807/1560-7917.ES.2019.24.49.1900237,PMC6905299,31822327,CC BY,"BACKGROUND: Timely notification of infectious diseases is essential for effective disease control and needs regular evaluation. AIM: Our objective was to evaluate the effects that statutory adjustments in the Netherlands in 2008 and raising awareness during outbreaks had on notification timeliness. METHODS: In a retrospective analyses of routine surveillance data obtained between July 2003 and November 2017, delays between disease onset and laboratory confirmation (disease identification delay), between laboratory confirmation and notification to Municipal Health Services (notification delay) and between notification and reporting to the National Institute for Public Health and the Environment (reporting delay) were analysed for 28 notifiable diseases. Delays before (period 1) and after the law change (periods 2 and 3) were compared with legal timeframes. We studied the effect of outbreak awareness in 10 outbreaks and the effect of specific guidance messages on disease identification delay for two diseases. RESULTS: We included 144,066 notifications. Average notification delay decreased from 1.4 to 0.4 days across the three periods (six diseases; p < 0.05), reporting delay decreased mainly in period 2 (from 0.5 to 0.1 days, six diseases; p < 0.05). In 2016–2017, legal timeframes were met overall. Awareness resulted in decreased disease identification delay for three diseases: measles and rubella (outbreaks) and psittacosis (specific guidance messages). CONCLUSIONS: Legal adjustments decreased notification and reporting delays, increased awareness reduced identification delays. As disease identification delay dominates the notification chain, insight in patient, doctor and laboratory delay is necessary to further improve timeliness and monitor the impact of control measures during outbreaks.",2019 Dec 5,"['Swaan, Corien M', 'Wong, Albert', 'Bonačić Marinović, Axel', 'Kretzschmar, Mirjam EE', 'van Steenbergen, Jim E']",Euro Surveill,,,True
29e94dee0df31f591c6f09c590e4c3523a14e647,PMC,IL-4/IL-13 polarization of macrophages enhances Ebola virus glycoprotein-dependent infection,http://dx.doi.org/10.1371/journal.pntd.0007819,PMC6905523,31825972,CC BY,"BACKGROUND: Ebolavirus (EBOV) outbreaks, while sporadic, cause tremendous morbidity and mortality. No therapeutics or vaccines are currently licensed; however, a vaccine has shown promise in clinical trials. A critical step towards development of effective therapeutics is a better understanding of factors that govern host susceptibility to this pathogen. As macrophages are an important cell population targeted during virus replication, we explore the effect of cytokine polarization on macrophage infection. METHODS/MAIN FINDINGS: We utilized a BSL2 EBOV model virus, infectious, recombinant vesicular stomatitis virus encoding EBOV glycoprotein (GP) (rVSV/EBOV GP) in place of its native glycoprotein. Macrophages polarized towards a M2-like anti-inflammatory state by combined IL-4 and IL-13 treatment were more susceptible to rVSV/EBOV GP, but not to wild-type VSV (rVSV/G), suggesting that EBOV GP-dependent entry events were enhanced by these cytokines. Examination of RNA expression of known surface receptors that bind and internalize filoviruses demonstrated that IL-4/IL-13 stimulated expression of the C-type lectin receptor DC-SIGN in human macrophages and addition of the competitive inhibitor mannan abrogated IL-4/IL-13 enhanced infection. Two murine DC-SIGN-like family members, SIGNR3 and SIGNR5, were upregulated by IL-4/IL-13 in murine macrophages, but only SIGNR3 enhanced virus infection in a mannan-inhibited manner, suggesting that murine SIGNR3 plays a similar role to human DC-SIGN. In vivo IL-4/IL-13 administration significantly increased virus-mediated mortality in a mouse model and transfer of ex vivo IL-4/IL-13-treated murine peritoneal macrophages into the peritoneal cavity of mice enhanced pathogenesis. SIGNIFICANCE: These studies highlight the ability of macrophage polarization to influence EBOV GP-dependent virus replication in vivo and ex vivo, with M2a polarization upregulating cell surface receptor expression and thereby enhancing virus replication. Our findings provide an increased understanding of the host factors in macrophages governing susceptibility to filoviruses and identify novel murine receptors mediating EBOV entry.",2019 Dec 11,"['Rogers, Kai J.', 'Brunton, Bethany', 'Mallinger, Laura', 'Bohan, Dana', 'Sevcik, Kristina M.', 'Chen, Jing', 'Ruggio, Natalie', 'Maury, Wendy']",PLoS Negl Trop Dis,,,True
02276a07ed2aa49afe07d97e7d7286b2b6fea532,PMC,Intracellular sensing of viral genomes and viral evasion,http://dx.doi.org/10.1038/s12276-019-0299-y,PMC6906418,31827068,CC BY,"During viral infection, virus-derived cytosolic nucleic acids are recognized by host intracellular specific sensors. The efficacy of this recognition system is crucial for triggering innate host defenses, which then stimulate more specific adaptive immune responses against the virus. Recent studies show that signal transduction pathways activated by sensing proteins are positively or negatively regulated by many modulators to maintain host immune homeostasis. However, viruses have evolved several strategies to counteract/evade host immune reactions. These systems involve viral proteins that interact with host sensor proteins and prevent them from detecting the viral genome or from initiating immune signaling. In this review, we discuss key regulators of cytosolic sensor proteins and viral proteins based on experimental evidence.",2019 Dec 11,"['Lee, Hyun-Cheol', 'Chathuranga, Kiramage', 'Lee, Jong-Soo']",Exp Mol Med,,,True
5372cbd6942c5451b9a48d018a2bd0b44207b469,PMC,Possible role of highly activated mucosal NK cells against viral respiratory infections in children undergoing haematopoietic stem cell transplantation,http://dx.doi.org/10.1038/s41598-019-55398-y,PMC6906525,31827202,CC BY,"Infection is the leading cause of non-relapse-related mortality after allogeneic haematopoietic stem cell transplantation (HSCT). Altered functions of immune cells in nasal secretions may influence post HSCT susceptibility to viral respiratory infections. In this prospective study, we determined T and NK cell numbers together with NK activation status in nasopharyngeal aspirates (NPA) in HSCT recipients and healthy controls using multiparametric flow cytometry. We also determined by polymerase chain reaction (PCR) the presence of 16 respiratory viruses. Samples were collected pre-HSCT, at day 0, +10, +20 and +30 after HSCT. Peripheral blood (PB) was also analyzed to determine T and NK cell numbers. A total of 27 pediatric HSCT recipients were enrolled and 16 of them had at least one viral detection (60%). Rhinovirus was the most frequent pathogen (84% of positive NPAs). NPAs of patients contained fewer T and NK cells compared to healthy controls (p = 0.0132 and p = 0.120, respectively). Viral PCR + patients showed higher NK cell number in their NPAs. The activating receptors repertoire expressed by NK cells was also higher in NPA samples, especially NKp44 and NKp46. Our study supports NK cells relevance for the immune defense against respiratory viruses in HSCT recipients.",2019 Dec 11,"['Vela, Maria', 'del Rosal, Teresa', 'Pérez-Martínez, Antonio', 'Valentín, Jaime', 'Casas, Inmaculada', 'Pozo, Francisco', 'Reinoso-Barbero, Francisco', 'Bueno, David', 'Corral, Dolores', 'Méndez-Echevarría, Ana', 'Mozo, Yasmina', 'Calvo, Cristina']",Sci Rep,,,False
0741533a3a9c97880fb1d7f184d569a6e5191ef1,PMC,Possible role of highly activated mucosal NK cells against viral respiratory infections in children undergoing haematopoietic stem cell transplantation,http://dx.doi.org/10.1038/s41598-019-55398-y,PMC6906525,31827202,CC BY,"Infection is the leading cause of non-relapse-related mortality after allogeneic haematopoietic stem cell transplantation (HSCT). Altered functions of immune cells in nasal secretions may influence post HSCT susceptibility to viral respiratory infections. In this prospective study, we determined T and NK cell numbers together with NK activation status in nasopharyngeal aspirates (NPA) in HSCT recipients and healthy controls using multiparametric flow cytometry. We also determined by polymerase chain reaction (PCR) the presence of 16 respiratory viruses. Samples were collected pre-HSCT, at day 0, +10, +20 and +30 after HSCT. Peripheral blood (PB) was also analyzed to determine T and NK cell numbers. A total of 27 pediatric HSCT recipients were enrolled and 16 of them had at least one viral detection (60%). Rhinovirus was the most frequent pathogen (84% of positive NPAs). NPAs of patients contained fewer T and NK cells compared to healthy controls (p = 0.0132 and p = 0.120, respectively). Viral PCR + patients showed higher NK cell number in their NPAs. The activating receptors repertoire expressed by NK cells was also higher in NPA samples, especially NKp44 and NKp46. Our study supports NK cells relevance for the immune defense against respiratory viruses in HSCT recipients.",2019 Dec 11,"['Vela, Maria', 'del Rosal, Teresa', 'Pérez-Martínez, Antonio', 'Valentín, Jaime', 'Casas, Inmaculada', 'Pozo, Francisco', 'Reinoso-Barbero, Francisco', 'Bueno, David', 'Corral, Dolores', 'Méndez-Echevarría, Ana', 'Mozo, Yasmina', 'Calvo, Cristina']",Sci Rep,,,True
4bcd826716cefe4fbd8aecfda57a14ce69c4f7e5,PMC,Survey of Traveler's Diarrhea: Epidemiology and Testing Reveal the Source,http://dx.doi.org/10.1155/2019/3569840,PMC6906815,31871514,CC BY,"OBJECTIVE: To understand the causes and transmission routes of, as well as risk factors, for a Salmonella outbreak in a tour group. METHOD: A retrospective cohort design was used to conduct an epidemiological field investigation. Real-time fluorescent quantitative PCR, bacterial culture, and serological identification methods were used for pathogen detection and identification. RESULT: There were 7 cases of illness, and the attack rate was 46.67%. The onset date was concentrated on May 9 and 10. All cases were found in the tour group, and no cases occurred in the nontour group. The results of this retrospective cohort study showed that the consumption of boiled eggs for breakfast on May 9 was a common factor (R(2) = 6.67, P=0.023). Salmonella enteritidis was identified from the patients' stool and vomit. CONCLUSION: The food poisoning epidemic was caused by Salmonella enteritidis. In the summer and autumn, attention should be paid to preservation, processing, and cooking of food to avoid bacterial contamination. To prevent sickness, travelers should know the disease prevalence at their destinations in advance.",2019 Nov 29,"['Gao, Zhenguo', 'Mahe, Muti', 'Tuohetamu, Shabiremu', 'Li, Fang', 'Zhang, Jian', 'Xia, Yidan', 'Sun, Xiaona', 'Naerkezi, Abuzhalihan', 'Huang, Ruifang', 'Liu, Hongbin', 'Ni, Daxin', 'Zhang, Rong']",Can J Infect Dis Med Microbiol,,,True
2cd9b37d110968368ce6f837e002788ac6158af8,PMC,Under-reporting of TB cases and associated factors: a case study in China,http://dx.doi.org/10.1186/s12889-019-8009-1,PMC6907198,31829147,CC BY,"BACKGROUND: Tuberculosis is a leading cause of death worldwide and has become a high global health priority. Accurate country level surveillance is critical to ending the pandemic. Effective routine reporting systems which track the course of the epidemic are vital in addressing TB. China, which has the third largest TB epidemic in the world and has developed a reporting system to help with the control and prevention of TB, this study examined its effectiveness in Eastern China. METHODS: The number of TB cases reported internally in two hospitals in Eastern China were compared to the number TB cases reported by these same hospitals in the national reporting systems in order to assess the accuracy of reporting. Qualitative data from interviews with key health officials and researcher experience using the TB reporting systems were used to identify factors affecting the accuracy of TB cases being reported in the national systems. RESULTS: This study found that over a quarter of TB cases recorded in the internal hospital records were not entered into the national TB reporting systems, leading to an under representation of national TB cases. Factors associated with underreporting included unqualified and overworked health personnel, poor supervision and accountability at local and national levels, and a complicated incohesive health information management system. CONCLUSIONS: This study demonstrates that TB in Eastern China is being underreported. Given that Eastern China is a developed province, one could assume similar problems may be found in other parts of China with fewer resources as well as many low- and middle-income countries. Having an accurate account of the number of national TB cases is essential to understanding the national and global burden of the disease and in managing TB prevention and control efforts. As such, factors associated with underreporting need to be addressed in order to reduce underreporting.",2019 Dec 11,"['Zhou, Danju', 'Pender, Michelle', 'Jiang, Weixi', 'Mao, Wenhui', 'Tang, Shenglan']",BMC Public Health,,,True
a57080f174e3ede5138af08070a2b9db8f9c36a7,PMC,Bat IFITM3 restriction depends on S-palmitoylation and a polymorphic site within the CD225 domain,http://dx.doi.org/10.26508/lsa.201900542,PMC6907390,31826928,CC BY,"Host interferon-induced transmembrane proteins (IFITMs) are broad-spectrum antiviral restriction factors. Of these, IFITM3 potently inhibits viruses that enter cells through acidic endosomes, many of which are zoonotic and emerging viruses with bats (order Chiroptera) as their natural hosts. We previously demonstrated that microbat IFITM3 is antiviral. Here, we show that bat IFITMs are characterized by strong adaptive evolution and identify a highly variable and functionally important site—codon 70—within the conserved CD225 domain of IFITMs. Mutation of this residue in microbat IFITM3 impairs restriction of representatives of four different virus families that enter cells via endosomes. This mutant shows altered subcellular localization and reduced S-palmitoylation, a phenotype copied by mutation of conserved cysteine residues in microbat IFITM3. Furthermore, we show that microbat IFITM3 is S-palmitoylated on cysteine residues C71, C72, and C105, mutation of each cysteine individually impairs virus restriction, and a triple C71A-C72A-C105A mutant loses all restriction activity, concomitant with subcellular re-localization of microbat IFITM3 to Golgi-associated sites. Thus, we propose that S-palmitoylation is critical for Chiropteran IFITM3 function and identify a key molecular determinant of IFITM3 S-palmitoylation.",2019 Dec 11,"['Benfield, Camilla TO', 'MacKenzie, Farrell', 'Ritzefeld, Markus', 'Mazzon, Michela', 'Weston, Stuart', 'Tate, Edward', 'Teo, Boon Han', 'Smith, Sarah E', 'Kellam, Paul', 'Holmes, Edward C', 'Marsh, Mark']",Life Sci Alliance,,,True
bd279c5846e21d317f62e33d3bd1d978c68a20e4,PMC,Bat IFITM3 restriction depends on S-palmitoylation and a polymorphic site within the CD225 domain,http://dx.doi.org/10.26508/lsa.201900542,PMC6907390,31826928,CC BY,"Host interferon-induced transmembrane proteins (IFITMs) are broad-spectrum antiviral restriction factors. Of these, IFITM3 potently inhibits viruses that enter cells through acidic endosomes, many of which are zoonotic and emerging viruses with bats (order Chiroptera) as their natural hosts. We previously demonstrated that microbat IFITM3 is antiviral. Here, we show that bat IFITMs are characterized by strong adaptive evolution and identify a highly variable and functionally important site—codon 70—within the conserved CD225 domain of IFITMs. Mutation of this residue in microbat IFITM3 impairs restriction of representatives of four different virus families that enter cells via endosomes. This mutant shows altered subcellular localization and reduced S-palmitoylation, a phenotype copied by mutation of conserved cysteine residues in microbat IFITM3. Furthermore, we show that microbat IFITM3 is S-palmitoylated on cysteine residues C71, C72, and C105, mutation of each cysteine individually impairs virus restriction, and a triple C71A-C72A-C105A mutant loses all restriction activity, concomitant with subcellular re-localization of microbat IFITM3 to Golgi-associated sites. Thus, we propose that S-palmitoylation is critical for Chiropteran IFITM3 function and identify a key molecular determinant of IFITM3 S-palmitoylation.",2019 Dec 11,"['Benfield, Camilla TO', 'MacKenzie, Farrell', 'Ritzefeld, Markus', 'Mazzon, Michela', 'Weston, Stuart', 'Tate, Edward', 'Teo, Boon Han', 'Smith, Sarah E', 'Kellam, Paul', 'Holmes, Edward C', 'Marsh, Mark']",Life Sci Alliance,,,False
ab3c4f88e655875b72719f078f4e1e4fd4459445,PMC,"A randomised clinical trial to evaluate the safety, fit, comfort of a novel N95 mask in children",http://dx.doi.org/10.1038/s41598-019-55451-w,PMC6908682,31831801,CC BY,"Children are more vulnerable to the risks of air pollution, including susceptibility to acquiring chronic diseases in their developing lungs. Despite these, there are no specific masks designed for and tested in children that are available to protect our young from the common particulate air pollutants today. We evaluated safety, fit and comfort of a specially designed paediatric N95 mask with an optional micro ventilator (micro fan, MF) in healthy children aged 7–14 years, in a randomized, two-period crossover design. The subjects’ cardiorespiratory physiological measurements were assessed in different states of physical activity under different interventions (mask without and with MF). A total of 106 subjects were recruited between July-August 2016. The use of the mask without MF increased the End-Tidal CO(2) (ETCO(2)) and Fractional concentration of Inspired CO(2) (FICO(2)) at rest and on mild exertion, as expected. The use of the mask with MF brought FICO(2) levels comparably closer to baseline levels without the mask for both activities. The mask, with or without the MF, was found to be well fitting, comfortable and safe for use in children at rest and on mild exertion. The N95 mask tested offers a promising start for more studies in the paediatric population.",2019 Dec 12,"['Goh, Daniel Yam Thiam', 'Mun, Meng Wai', 'Lee, Wei Liang Jerome', 'Teoh, Oon Hoe', 'Rajgor, Dimple D.']",Sci Rep,,,True
b8b5777e309626389bb1a1565dc36b2076733b0d,PMC,Effect of carbonization degree of carbon dots on cytotoxicity and photo-induced toxicity to cells,http://dx.doi.org/10.1016/j.heliyon.2019.e02940,PMC6909074,31872119,CC BY,"BACKGROUND: Pristine carbon dots (CDs) derived from citric acid pyrolysis are used in a variety of biomedical research such as imaging and drug delivery. However, potential cytotoxic effects of pyrolysis temperature on cells is underexplored. To address this need, we studied toxicity of the CDs to breast cancer cells using MTT and LDH assays. In addition, we investigated photo-induced cytotoxicity of the synthesized CDs in a wide concentration range under white light. RESULTS: Our results suggest little cytotoxicity of the CDs after 24 h exposure of cells. Only the high quantum yield CDs caused a significant toxicity to cells at the highest concentrations of 2.0 and 1.5 mg/ml compared to other CDs at similar concentrations. The synthesized CDs entered the cells without any significant cytotoxicity. The CDs also caused a concentration- and irradiation time-dependent photo-induced cytotoxicity. CONCLUSION: The optimization of synthesis conditions from this study may help develop safe and efficient CDs for imaging and drug delivery.",2019 Dec 5,"['Esfandiari, Neda', 'Bagheri, Zeinab', 'Ehtesabi, Hamide', 'Fatahi, Zahra', 'Tavana, Hossein', 'Latifi, Hamid']",Heliyon,,,False
9e953d462385492fa9cc2ada05c1fd357de8afed,PMC,CLEC2 and CLEC5A: Pathogenic Host Factors in Acute Viral Infections,http://dx.doi.org/10.3389/fimmu.2019.02867,PMC6909378,31867016,CC BY,"The protective roles of endosomal toll-like receptors (TLRs) and cytosolic nucleic acid sensors are well elucidated, but the pathogenic host factors during viral infections remain unclear. Spleen tyrosine kinase (Syk)-coupled C-type lectins (CLECs) CLEC2 and CLEC5A are highly expressed on platelets and myeloid cells, respectively. CLEC2 has been shown to recognize snake venom aggretin and the endogenous ligand podoplanin and acts as a critical regulator in the development and immunothrombosis. Although CLEC2 has been reported to interact with type I immunodeficiency virus (HIV-1), its role in viral infections is still unclear. CLEC5A binds to fucose and mannose moieties of dengue virus membrane glycans, as well as to N-acetylglucosamine (GlcNAc)/N-acetylmuramic acid (MurNAc) disaccharides that form the backbone of L. monocytogenes peptidoglycans. Recently, we demonstrated that both CLEC2 and CLEC5A are critical in microbe-induced “neutrophil extracellular trap” (NET) formation and proinflammatory cytokine production. Moreover, activation of CLEC2 by dengue virus (DV) and H5N1 influenza virus (IAV) induces the release of extracellular vesicles (EVs), which further enhance NETosis and proinflammatory cytokine production via CLEC5A and Toll-like receptor 2 (TLR2). These findings not only illustrate the immunomodulatory effects of EVs during platelet-leukocyte interactions, but also demonstrate the critical roles of CLEC2 and CLEC5A in acute viral infections.",2019 Dec 6,"['Sung, Pei-Shan', 'Hsieh, Shie-Liang']",Front Immunol,,,True
c38bc4bdbec2199031430ac3813398806a13a0a9,PMC,Development of Small-Molecule Inhibitors Against Zika Virus Infection,http://dx.doi.org/10.3389/fmicb.2019.02725,PMC6909824,31866959,CC BY,"In recent years, the outbreak of infectious disease caused by Zika virus (ZIKV) has posed a major threat to global public health, calling for the development of therapeutics to treat ZIKV disease. Here, we have described the different stages of the ZIKV life cycle and summarized the latest progress in the development of small-molecule inhibitors against ZIKV infection. We have also discussed some general strategies for the discovery of small-molecule ZIKV inhibitors.",2019 Dec 6,"['Wang, Lili', 'Liang, Ruiying', 'Gao, Yaning', 'Li, Yanbai', 'Deng, Xiaoqian', 'Xiang, Rong', 'Zhang, Yina', 'Ying, Tianlei', 'Jiang, Shibo', 'Yu, Fei']",Front Microbiol,,,True
70afb22f932f20c402dd57e6b09ea9c658a1b3a4,PMC,Occupational Animal Contact in Southern and Central Vietnam,http://dx.doi.org/10.1007/s10393-019-01444-0,PMC6910886,31720941,CC BY,"Despite the global zoonotic disease burden, the underlying exposures that drive zoonotic disease emergence are not understood. Here, we aimed to assess exposures to potential sources of zoonotic disease and investigate the demographics, attitudes, and behavior of individuals with sustained occupational animal contact in Vietnam. We recruited 581 animal workers (animal-raising farmers, slaughterers, animal health workers, and rat traders) and their families in southern and central Vietnam into a cohort. Cohort members were followed for 3 years and interviewed annually regarding (1) demography and attitudes regarding zoonotic disease, (2) medical history, (3) specific exposures to potential zoonotic infection sources, and (4) socioeconomic status. Interview information over the 3 years was combined and analyzed as cross-sectional data. Of the 297 cohort members interviewed, the majority (79.8%; 237/297) reported raising livestock; almost all (99.6%; 236/237) reported being routinely exposed to domestic animals, and more than a quarter (28.7%; 68/237) were exposed to exotic animals. Overall, 70% (208/297) reported slaughtering exotic animals; almost all (99.5%; 207/208) reported consuming such animals. The consumption of raw blood and meat was common (24.6%; 73/297 and 37%; 110/297, respectively). Over half (58.6%; 174/297) reported recent occupational animal-induced injuries that caused bleeding; the use of personal protective equipment (PPE) was limited. Our work demonstrates that individuals working with animals in Vietnam are exposed to a wide range of species, and there are limited procedures for reducing potential zoonotic disease exposures. We advocate better education, improved animal security, and enforced legislation of PPE for those with occupational animal exposure in Vietnam.",2019 Nov 13,"['Tu, Nguyen Thi Kha', 'Tue, Ngo Tri', 'Vapalahti, Olli', 'Virtala, Anna-Maija K.', 'Van Tan, Le', 'Rabaa, Maia A.', 'Carrique-Mas, Juan', 'Thwaites, Guy E.', 'Baker, Stephen', None]",Ecohealth,,,True
3f7bd4a924c211d594079b72b3bc699bdb086880,PMC,Structural insights into ubiquitin recognition and Ufd1 interaction of Npl4,http://dx.doi.org/10.1038/s41467-019-13697-y,PMC6910952,31836717,CC BY,"Npl4 is likely to be the most upstream factor recognizing Lys48-linked polyubiquitylated substrates in the proteasomal degradation pathway in yeast. Along with Ufd1, Npl4 forms a heterodimer (UN), and functions as a cofactor for the Cdc48 ATPase. Here, we report the crystal structures of yeast Npl4 in complex with Lys48-linked diubiquitin and with the Npl4-binding motif of Ufd1. The distal and proximal ubiquitin moieties of Lys48-linked diubiquitin primarily interact with the C-terminal helix and N-terminal loop of the Npl4 C-terminal domain (CTD), respectively. Mutational analysis suggests that the CTD contributes to linkage selectivity and initial binding of ubiquitin chains. Ufd1 occupies a hydrophobic groove of the Mpr1/Pad1 N-terminal (MPN) domain of Npl4, which corresponds to the catalytic groove of the MPN domain of JAB1/MPN/Mov34 metalloenzyme (JAMM)-family deubiquitylating enzyme. This study provides important structural insights into the polyubiquitin chain recognition by the Cdc48–UN complex and its assembly.",2019 Dec 13,"['Sato, Yusuke', 'Tsuchiya, Hikaru', 'Yamagata, Atsushi', 'Okatsu, Kei', 'Tanaka, Keiji', 'Saeki, Yasushi', 'Fukai, Shuya']",Nat Commun,,,False
7e9276889019ffaa4ca7bf5ac98673b07e60b147,PMC,Structural insights into ubiquitin recognition and Ufd1 interaction of Npl4,http://dx.doi.org/10.1038/s41467-019-13697-y,PMC6910952,31836717,CC BY,"Npl4 is likely to be the most upstream factor recognizing Lys48-linked polyubiquitylated substrates in the proteasomal degradation pathway in yeast. Along with Ufd1, Npl4 forms a heterodimer (UN), and functions as a cofactor for the Cdc48 ATPase. Here, we report the crystal structures of yeast Npl4 in complex with Lys48-linked diubiquitin and with the Npl4-binding motif of Ufd1. The distal and proximal ubiquitin moieties of Lys48-linked diubiquitin primarily interact with the C-terminal helix and N-terminal loop of the Npl4 C-terminal domain (CTD), respectively. Mutational analysis suggests that the CTD contributes to linkage selectivity and initial binding of ubiquitin chains. Ufd1 occupies a hydrophobic groove of the Mpr1/Pad1 N-terminal (MPN) domain of Npl4, which corresponds to the catalytic groove of the MPN domain of JAB1/MPN/Mov34 metalloenzyme (JAMM)-family deubiquitylating enzyme. This study provides important structural insights into the polyubiquitin chain recognition by the Cdc48–UN complex and its assembly.",2019 Dec 13,"['Sato, Yusuke', 'Tsuchiya, Hikaru', 'Yamagata, Atsushi', 'Okatsu, Kei', 'Tanaka, Keiji', 'Saeki, Yasushi', 'Fukai, Shuya']",Nat Commun,,,False
b02a2c1726c3d4dc716391bbe282874a57165ed1,PMC,Structural insights into ubiquitin recognition and Ufd1 interaction of Npl4,http://dx.doi.org/10.1038/s41467-019-13697-y,PMC6910952,31836717,CC BY,"Npl4 is likely to be the most upstream factor recognizing Lys48-linked polyubiquitylated substrates in the proteasomal degradation pathway in yeast. Along with Ufd1, Npl4 forms a heterodimer (UN), and functions as a cofactor for the Cdc48 ATPase. Here, we report the crystal structures of yeast Npl4 in complex with Lys48-linked diubiquitin and with the Npl4-binding motif of Ufd1. The distal and proximal ubiquitin moieties of Lys48-linked diubiquitin primarily interact with the C-terminal helix and N-terminal loop of the Npl4 C-terminal domain (CTD), respectively. Mutational analysis suggests that the CTD contributes to linkage selectivity and initial binding of ubiquitin chains. Ufd1 occupies a hydrophobic groove of the Mpr1/Pad1 N-terminal (MPN) domain of Npl4, which corresponds to the catalytic groove of the MPN domain of JAB1/MPN/Mov34 metalloenzyme (JAMM)-family deubiquitylating enzyme. This study provides important structural insights into the polyubiquitin chain recognition by the Cdc48–UN complex and its assembly.",2019 Dec 13,"['Sato, Yusuke', 'Tsuchiya, Hikaru', 'Yamagata, Atsushi', 'Okatsu, Kei', 'Tanaka, Keiji', 'Saeki, Yasushi', 'Fukai, Shuya']",Nat Commun,,,False
aed0e70359bffd12f9748dc4d900d9ec3a170422,PMC,Structural insights into ubiquitin recognition and Ufd1 interaction of Npl4,http://dx.doi.org/10.1038/s41467-019-13697-y,PMC6910952,31836717,CC BY,"Npl4 is likely to be the most upstream factor recognizing Lys48-linked polyubiquitylated substrates in the proteasomal degradation pathway in yeast. Along with Ufd1, Npl4 forms a heterodimer (UN), and functions as a cofactor for the Cdc48 ATPase. Here, we report the crystal structures of yeast Npl4 in complex with Lys48-linked diubiquitin and with the Npl4-binding motif of Ufd1. The distal and proximal ubiquitin moieties of Lys48-linked diubiquitin primarily interact with the C-terminal helix and N-terminal loop of the Npl4 C-terminal domain (CTD), respectively. Mutational analysis suggests that the CTD contributes to linkage selectivity and initial binding of ubiquitin chains. Ufd1 occupies a hydrophobic groove of the Mpr1/Pad1 N-terminal (MPN) domain of Npl4, which corresponds to the catalytic groove of the MPN domain of JAB1/MPN/Mov34 metalloenzyme (JAMM)-family deubiquitylating enzyme. This study provides important structural insights into the polyubiquitin chain recognition by the Cdc48–UN complex and its assembly.",2019 Dec 13,"['Sato, Yusuke', 'Tsuchiya, Hikaru', 'Yamagata, Atsushi', 'Okatsu, Kei', 'Tanaka, Keiji', 'Saeki, Yasushi', 'Fukai, Shuya']",Nat Commun,,,True
90d54e33891390c4539182390d2976123d5ddc2a,PMC,A database of geopositioned Middle East Respiratory Syndrome Coronavirus occurrences,http://dx.doi.org/10.1038/s41597-019-0330-0,PMC6911100,31836720,CC BY,"As a World Health Organization Research and Development Blueprint priority pathogen, there is a need to better understand the geographic distribution of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and its potential to infect mammals and humans. This database documents cases of MERS-CoV globally, with specific attention paid to zoonotic transmission. An initial literature search was conducted in PubMed, Web of Science, and Scopus; after screening articles according to the inclusion/exclusion criteria, a total of 208 sources were selected for extraction and geo-positioning. Each MERS-CoV occurrence was assigned one of the following classifications based upon published contextual information: index, unspecified, secondary, mammal, environmental, or imported. In total, this database is comprised of 861 unique geo-positioned MERS-CoV occurrences. The purpose of this article is to share a collated MERS-CoV database and extraction protocol that can be utilized in future mapping efforts for both MERS-CoV and other infectious diseases. More broadly, it may also provide useful data for the development of targeted MERS-CoV surveillance, which would prove invaluable in preventing future zoonotic spillover.",2019 Dec 13,"['Ramshaw, Rebecca E.', 'Letourneau, Ian D.', 'Hong, Amy Y.', 'Hon, Julia', 'Morgan, Julia D.', 'Osborne, Joshua C. P.', 'Shirude, Shreya', 'Van Kerkhove, Maria D.', 'Hay, Simon I.', 'Pigott, David M.']",Sci Data,,,True
6a6032614741732c373d0a939ce85785519c3fa6,PMC,Recombinant Rotaviruses Rescued by Reverse Genetics Reveal the Role of NSP5 Hyperphosphorylation in the Assembly of Viral Factories,http://dx.doi.org/10.1128/JVI.01110-19,PMC6912106,31619556,CC BY,"Rotavirus (RV) replicates in round-shaped cytoplasmic viral factories, although how they assemble remains unknown. During RV infection, NSP5 undergoes hyperphosphorylation, which is primed by the phosphorylation of a single serine residue. The role of this posttranslational modification in the formation of viroplasms and its impact on virus replication remain obscure. Here, we investigated the role of NSP5 during RV infection by taking advantage of a modified fully tractable reverse-genetics system. A trans-complementing cell line stably producing NSP5 was used to generate and characterize several recombinant rotaviruses (rRVs) with mutations in NSP5. We demonstrate that an rRV lacking NSP5 was completely unable to assemble viroplasms and to replicate, confirming its pivotal role in rotavirus replication. A number of mutants with impaired NSP5 phosphorylation were generated to further interrogate the function of this posttranslational modification in the assembly of replication-competent viroplasms. We showed that the rRV mutant strains exhibited impaired viral replication and the ability to assemble round-shaped viroplasms in MA104 cells. Furthermore, we investigated the mechanism of NSP5 hyperphosphorylation during RV infection using NSP5 phosphorylation-negative rRV strains, as well as MA104-derived stable transfectant cell lines expressing either wild-type NSP5 or selected NSP5 deletion mutants. Our results indicate that NSP5 hyperphosphorylation is a crucial step for the assembly of round-shaped viroplasms, highlighting the key role of the C-terminal tail of NSP5 in the formation of replication-competent viral factories. Such a complex NSP5 phosphorylation cascade may serve as a paradigm for the assembly of functional viral factories in other RNA viruses. IMPORTANCE The rotavirus (RV) double-stranded RNA genome is replicated and packaged into virus progeny in cytoplasmic structures termed viroplasms. The nonstructural protein NSP5, which undergoes a complex hyperphosphorylation process during RV infection, is required for the formation of these virus-induced organelles. However, its roles in viroplasm formation and RV replication have never been directly assessed due to the lack of a fully tractable reverse-genetics (RG) system for rotaviruses. Here, we show a novel application of a recently developed RG system by establishing a stable trans-complementing NSP5-producing cell line required to rescue rotaviruses with mutations in NSP5. This approach allowed us to provide the first direct evidence of the pivotal role of this protein during RV replication. Furthermore, using recombinant RV mutants, we shed light on the molecular mechanism of NSP5 hyperphosphorylation during infection and its involvement in the assembly and maturation of replication-competent viroplasms.",2019 Dec 12,"['Papa, Guido', 'Venditti, Luca', 'Arnoldi, Francesca', 'Schraner, Elisabeth M.', 'Potgieter, Christiaan', 'Borodavka, Alexander', 'Eichwald, Catherine', 'Burrone, Oscar R.']",J Virol,,,True
18f3146e3ad376486f1ade8e5c89c086d434620a,PMC,Recent Advances in EPAC-Targeted Therapies: A Biophysical Perspective,http://dx.doi.org/10.3390/cells8111462,PMC6912387,31752286,CC BY,"The universal second messenger cAMP regulates diverse intracellular processes by interacting with ubiquitously expressed proteins, such as Protein Kinase A (PKA) and the Exchange Protein directly Activated by cAMP (EPAC). EPAC is implicated in multiple pathologies, thus several EPAC-specific inhibitors have been identified in recent years. However, the mechanisms and molecular interactions underlying the EPAC inhibition elicited by such compounds are still poorly understood. Additionally, being hydrophobic low molecular weight species, EPAC-specific inhibitors are prone to forming colloidal aggregates, which result in non-specific aggregation-based inhibition (ABI) in aqueous systems. Here, we review from a biophysical perspective the molecular basis of the specific and non-specific interactions of two EPAC antagonists—CE3F4R, a non-competitive inhibitor, and ESI-09, a competitive inhibitor of EPAC. Additionally, we discuss the value of common ABI attenuators (e.g., TX and HSA) to reduce false positives at the expense of introducing false negatives when screening aggregation-prone compounds. We hope this review provides the EPAC community effective criteria to evaluate similar compounds, aiding in the optimization of existing drug leads, and informing the development of the next generation of EPAC-specific inhibitors.",2019 Nov 19,"['Ahmed, Alveena', 'Boulton, Stephen', 'Shao, Hongzhao', 'Akimoto, Madoka', 'Natarajan, Amarnath', 'Cheng, Xiaodong', 'Melacini, Giuseppe']",Cells,,,True
ad24f286c7ec0d2bc7da77cc35036a3c14982221,PMC,Role for migratory domestic poultry and/or wild birds in the global spread of avian influenza?,http://dx.doi.org/10.1080/01652176.2019.1697013,PMC6913625,31752591,CC BY,,2019 Nov 22,"van der Kolk, Johannes H.",Vet Q,,,True
ea1eff3e4dd61110688eb2c07a616443dee8867b,PMC,Co-infection with Bartonella henselae and Sarcocystis sp. in a 6-year-old male neutered domestic longhair cat with progressive multifocal neurological signs,http://dx.doi.org/10.1080/01652176.2019.1697012,PMC6913637,31822209,CC BY,,2019 Dec 10,"['Castel, Aude', 'Olby, Natasha J.', 'Breitschwerdt, Edward B.', 'Thomas, Brittany', 'Maggi, Ricardo G.', 'Shelton, G. Diane']",Vet Q,,,True
b0b3e5ed41b073e7b77364c196beba10827b1df4,PMC,Trustworthy Health-Related Tweets on Social Media in Saudi Arabia: Tweet Metadata Analysis,http://dx.doi.org/10.2196/14731,PMC6914129,31596242,CC BY,"BACKGROUND: Social media platforms play a vital role in the dissemination of health information. However, evidence suggests that a high proportion of Twitter posts (ie, tweets) are not necessarily accurate, and many studies suggest that tweets do not need to be accurate, or at least evidence based, to receive traction. This is a dangerous combination in the sphere of health information. OBJECTIVE: The first objective of this study is to examine health-related tweets originating from Saudi Arabia in terms of their accuracy. The second objective is to find factors that relate to the accuracy and dissemination of these tweets, thereby enabling the identification of ways to enhance the dissemination of accurate tweets. The initial findings from this study and methodological improvements will then be employed in a larger-scale study that will address these issues in more detail. METHODS: A health lexicon was used to extract health-related tweets using the Twitter application programming interface and the results were further filtered manually. A total of 300 tweets were each labeled by two medical doctors; the doctors agreed that 109 tweets were either accurate or inaccurate. Other measures were taken from these tweets’ metadata to see if there was any relationship between the measures and either the accuracy or the dissemination of the tweets. The entire range of this metadata was analyzed using Python, version 3.6.5 (Python Software Foundation), to answer the research questions posed. RESULTS: A total of 34 out of 109 tweets (31.2%) in the dataset used in this study were classified as untrustworthy health information. These came mainly from users with a non-health care background and social media accounts that had no corresponding physical (ie, organization) manifestation. Unsurprisingly, we found that traditionally trusted health sources were more likely to tweet accurate health information than other users. Likewise, these provisional results suggest that tweets posted in the morning are more trustworthy than tweets posted at night, possibly corresponding to official and casual posts, respectively. Our results also suggest that the crowd was quite good at identifying trustworthy information sources, as evidenced by the number of times a tweet’s author was tagged as favorited by the community. CONCLUSIONS: The results indicate some initially surprising factors that might correlate with the accuracy of tweets and their dissemination. For example, the time a tweet was posted correlated with its accuracy, which may reflect a difference between professional (ie, morning) and hobbyist (ie, evening) tweets. More surprisingly, tweets containing a kashida—a decorative element in Arabic writing used to justify the text within lines—were more likely to be disseminated through retweets. These findings will be further assessed using data analysis techniques on a much larger dataset in future work.",2019 Oct 8,"['Albalawi, Yahya', 'Nikolov, Nikola S', 'Buckley, Jim']",J Med Internet Res,,,False
772c168e0f1f2665813a4fd00565caddbbd89750,PMC,Trustworthy Health-Related Tweets on Social Media in Saudi Arabia: Tweet Metadata Analysis,http://dx.doi.org/10.2196/14731,PMC6914129,31596242,CC BY,"BACKGROUND: Social media platforms play a vital role in the dissemination of health information. However, evidence suggests that a high proportion of Twitter posts (ie, tweets) are not necessarily accurate, and many studies suggest that tweets do not need to be accurate, or at least evidence based, to receive traction. This is a dangerous combination in the sphere of health information. OBJECTIVE: The first objective of this study is to examine health-related tweets originating from Saudi Arabia in terms of their accuracy. The second objective is to find factors that relate to the accuracy and dissemination of these tweets, thereby enabling the identification of ways to enhance the dissemination of accurate tweets. The initial findings from this study and methodological improvements will then be employed in a larger-scale study that will address these issues in more detail. METHODS: A health lexicon was used to extract health-related tweets using the Twitter application programming interface and the results were further filtered manually. A total of 300 tweets were each labeled by two medical doctors; the doctors agreed that 109 tweets were either accurate or inaccurate. Other measures were taken from these tweets’ metadata to see if there was any relationship between the measures and either the accuracy or the dissemination of the tweets. The entire range of this metadata was analyzed using Python, version 3.6.5 (Python Software Foundation), to answer the research questions posed. RESULTS: A total of 34 out of 109 tweets (31.2%) in the dataset used in this study were classified as untrustworthy health information. These came mainly from users with a non-health care background and social media accounts that had no corresponding physical (ie, organization) manifestation. Unsurprisingly, we found that traditionally trusted health sources were more likely to tweet accurate health information than other users. Likewise, these provisional results suggest that tweets posted in the morning are more trustworthy than tweets posted at night, possibly corresponding to official and casual posts, respectively. Our results also suggest that the crowd was quite good at identifying trustworthy information sources, as evidenced by the number of times a tweet’s author was tagged as favorited by the community. CONCLUSIONS: The results indicate some initially surprising factors that might correlate with the accuracy of tweets and their dissemination. For example, the time a tweet was posted correlated with its accuracy, which may reflect a difference between professional (ie, morning) and hobbyist (ie, evening) tweets. More surprisingly, tweets containing a kashida—a decorative element in Arabic writing used to justify the text within lines—were more likely to be disseminated through retweets. These findings will be further assessed using data analysis techniques on a much larger dataset in future work.",2019 Oct 8,"['Albalawi, Yahya', 'Nikolov, Nikola S', 'Buckley, Jim']",J Med Internet Res,,,False
98f9843f4b024272b6514db6e53546839101a839,PMC,Spatially Adjusted Time-varying Reproductive Numbers: Understanding the Geographical Expansion of Urban Dengue Outbreaks,http://dx.doi.org/10.1038/s41598-019-55574-0,PMC6914775,31844099,CC BY,"The basic reproductive number (R(0)) is a fundamental measure used to quantify the transmission potential of an epidemic in public health practice. However, R(0) cannot reflect the time-varying nature of an epidemic. A time-varying effective reproductive number R(t) can provide more information because it tracks the subsequent evolution of transmission. However, since it neglects individual-level geographical variations in exposure risk, R(t) may smooth out interpersonal heterogeneous transmission potential, obscure high-risk spreaders, and hence hamper the effectiveness of control measures in spatial dimension. Therefore, this study proposes a new method for quantifying spatially adjusted (time-varying) reproductive numbers that reflects spatial heterogeneity in transmission potential among individuals. This new method estimates individual-level effective reproductive numbers (R(j)) and a summarized indicator for population-level time-varying reproductive number (R(t)). Data from the five most severe dengue outbreaks in southern Taiwan from 1998–2015 were used to demonstrate the ability of the method to highlight early spreaders contributing to the geographic expansion of dengue transmission. Our results show spatial heterogeneity in the transmission potential of dengue among individuals and identify the spreaders with the highest R(j) during the epidemic period. The results also reveal that super-spreaders are usually early spreaders that locate at the edges of the epidemic foci, which means that these cases could be the drivers of the expansion of the outbreak. Therefore, our proposed method depicts a more detailed spatial-temporal dengue transmission process and identifies the significant role of the edges of the epidemic foci, which could be weak spots in disease control and prevention.",2019 Dec 16,"['Ng, Ta-Chou', 'Wen, Tzai-Hung']",Sci Rep,,,True
0ca5279816f66f7fd8c0bdb09d15f5953e019b68,PMC,Comparative Study of Microbiological Monitoring Results from Three Types of Sampling Methods after Gastrointestinal Endoscope Reprocessing,http://dx.doi.org/10.1155/2019/7940468,PMC6914964,31886251,CC BY,"OBJECTIVE: Compare the effects of three sampling methods on the microbiological monitoring results after reprocessing of gastrointestinal endoscopes, providing scientific basis for improving the monitoring quality of gastrointestinal endoscope cleaning and disinfection. METHOD: Gastrointestinal endoscopes after reprocessing were selected randomly at the gastrointestinal endoscopy center of a tertiary hospital in Shanghai from October 2018 to February 2019. The endoscopes selected were all sampled in three different methods under continuous sampling and intermittent sampling respectively. Methods used includes, the biopsy channel group (Group A), the entire channel group (Group B), and the disc brush group (Group C). Then the colony forming units (CFU/piece) were counted in the laboratory. RESULTS: A total of 12 endoscopes were sampled by using continuous sampling approach, in which the detection rate of bacteria in disc brush group (33.3%) and entire channel group (33.3%) was higher than biopsy channel group (8.3%). Among the 12 endoscopes sampled with intermittent approach, the detection rate of bacteria from high to low was the disc brush group (50%), the entire channel group (41.7%), and the biopsy channel group (8.3%). CONCLUSION: Different sampling methods will lead to the difference of microbiological culture results after reprocessing of gastrointestinal endoscope, indicating that the improved sampling method is beneficial to objectively reflect the endoscope cleaning and disinfection effect, and improve the monitoring quality of endoscope disinfection.",2019 Dec 3,"['Ma, Su', 'Feng, Lili', 'Jiang, Ziyi', 'Gao, Xian', 'Long, Xisha', 'Zhuang, Shaonan', 'Ding, Wenxia', 'Chen, Taiyao', 'Li, Zhaoshen', 'Zhang, Lingjuan', 'Xi, Huijun', 'Zhang, Hongzhi']",Biomed Res Int,,,True
0c1318a0ed68a50f13ef04c2cd0741d2e7016104,PMC,Cas12a-Based On-Site and Rapid Nucleic Acid Detection of African Swine Fever,http://dx.doi.org/10.3389/fmicb.2019.02830,PMC6916198,31921018,CC BY,"The mortality rate of hemorrhagic African swine fever (ASF), which targets domestic pigs and wild boars is caused by African swine fever virus (ASFV), can reach 100%. Since the first confirmed ASF outbreak in China on 3 August 2018, 156 ASF outbreaks were detected in 32 provinces. About 1,170,000 pigs were culled in order to halt further spread. There is no effective treatment or vaccine for it and the present molecular diagnosis technologies have trade-offs in sensitivity, specificity, cost and speed, and none of them cater perfectly to ASF control. Thus, a technology that overcomes the need for laboratory facilities, is relatively low cost, and rapidly and sensitively detects ASFV would be highly valuable. Here, we describe an RAA-Cas12a-based system that combines recombinase aided amplification (RAA) and CRISPR/Cas12a for ASFV detection. The fluorescence intensity readout of this system detected ASFV p72 gene levels as low as 10 aM. For on-site ASFV detection, lateral-flow strip readout was introduced for the first time in the RAA-Cas12a based system (named CORDS, Cas12a-based On-site and Rapid Detection System). We used CORDS to detect target DNA highly specifically using the lateral-flow strip readout and the assay displayed no cross-reactivity to other 13 swine viruses including classical swine fever (CSF). CORDS could identify the ASFV DNA target at femtomolar sensitivity in an hour at 37°C, and only requires an incubator. For ease of use, the reagents of CORDS were lyophilized to three tubes and remained the same sensitivity when stored at 4°C for at least 7 days. Thus, CORDS provide a rapid, sensitive and easily operable method for ASFV on-site detection. Lyophilized CORDS can withstand long-term transportation and storage, and is ready for field-based applications.",2019 Dec 10,"['Bai, Jing', 'Lin, Haosi', 'Li, Haojian', 'Zhou, Yang', 'Liu, Junshan', 'Zhong, Guorui', 'Wu, Luting', 'Jiang, Weifan', 'Du, Hongli', 'Yang, Jinyi', 'Xie, Qingmei', 'Huang, Lizhen']",Front Microbiol,,,True
6eb1223ecff4a2f876742c88220cbfbc4e27d0e9,PMC,Genetic deletion of Sphk2 confers protection against Pseudomonas aeruginosa mediated differential expression of genes related to virulent infection and inflammation in mouse lung,http://dx.doi.org/10.1186/s12864-019-6367-9,PMC6916461,31842752,CC BY,"BACKGROUND: Pseudomonas aeruginosa (PA) is an opportunistic Gram-negative bacterium that causes serious life threatening and nosocomial infections including pneumonia. PA has the ability to alter host genome to facilitate its invasion, thus increasing the virulence of the organism. Sphingosine-1- phosphate (S1P), a bioactive lipid, is known to play a key role in facilitating infection. Sphingosine kinases (SPHK) 1&2 phosphorylate sphingosine to generate S1P in mammalian cells. We reported earlier that Sphk2(−/−) mice offered significant protection against lung inflammation, compared to wild type (WT) animals. Therefore, we profiled the differential expression of genes between the protected group of Sphk2(−/−) and the wild type controls to better understand the underlying protective mechanisms related to the Sphk2 deletion in lung inflammatory injury. Whole transcriptome shotgun sequencing (RNA-Seq) was performed on mouse lung tissue using NextSeq 500 sequencing system. RESULTS: Two-way analysis of variance (ANOVA) analysis was performed and differentially expressed genes following PA infection were identified using whole transcriptome of Sphk2(−/−) mice and their WT counterparts. Pathway (PW) enrichment analyses of the RNA seq data identified several signaling pathways that are likely to play a crucial role in pneumonia caused by PA such as those involved in: 1. Immune response to PA infection and NF-κB signal transduction; 2. PKC signal transduction; 3. Impact on epigenetic regulation; 4. Epithelial sodium channel pathway; 5. Mucin expression; and 6. Bacterial infection related pathways. Our genomic data suggests a potential role for SPHK2 in PA-induced pneumonia through elevated expression of inflammatory genes in lung tissue. Further, validation by RT-PCR on 10 differentially expressed genes showed 100% concordance in terms of vectoral changes as well as significant fold change. CONCLUSION: Using Sphk2(−/−) mice and differential gene expression analysis, we have shown here that S1P/SPHK2 signaling could play a key role in promoting PA pneumonia. The identified genes promote inflammation and suppress others that naturally inhibit inflammation and host defense. Thus, targeting SPHK2/S1P signaling in PA-induced lung inflammation could serve as a potential therapy to combat PA-induced pneumonia.",2019 Dec 16,"['Ebenezer, David L.', 'Fu, Panfeng', 'Krishnan, Yashaswin', 'Maienschein-Cline, Mark', 'Hu, Hong', 'Jung, Segun', 'Madduri, Ravi', 'Arbieva, Zarema', 'Harijith, Anantha', 'Natarajan, Viswanathan']",BMC Genomics,,,False
52e083e335c8c29b8867ac67d5090b71348f2eac,PMC,Genetic deletion of Sphk2 confers protection against Pseudomonas aeruginosa mediated differential expression of genes related to virulent infection and inflammation in mouse lung,http://dx.doi.org/10.1186/s12864-019-6367-9,PMC6916461,31842752,CC BY,"BACKGROUND: Pseudomonas aeruginosa (PA) is an opportunistic Gram-negative bacterium that causes serious life threatening and nosocomial infections including pneumonia. PA has the ability to alter host genome to facilitate its invasion, thus increasing the virulence of the organism. Sphingosine-1- phosphate (S1P), a bioactive lipid, is known to play a key role in facilitating infection. Sphingosine kinases (SPHK) 1&2 phosphorylate sphingosine to generate S1P in mammalian cells. We reported earlier that Sphk2(−/−) mice offered significant protection against lung inflammation, compared to wild type (WT) animals. Therefore, we profiled the differential expression of genes between the protected group of Sphk2(−/−) and the wild type controls to better understand the underlying protective mechanisms related to the Sphk2 deletion in lung inflammatory injury. Whole transcriptome shotgun sequencing (RNA-Seq) was performed on mouse lung tissue using NextSeq 500 sequencing system. RESULTS: Two-way analysis of variance (ANOVA) analysis was performed and differentially expressed genes following PA infection were identified using whole transcriptome of Sphk2(−/−) mice and their WT counterparts. Pathway (PW) enrichment analyses of the RNA seq data identified several signaling pathways that are likely to play a crucial role in pneumonia caused by PA such as those involved in: 1. Immune response to PA infection and NF-κB signal transduction; 2. PKC signal transduction; 3. Impact on epigenetic regulation; 4. Epithelial sodium channel pathway; 5. Mucin expression; and 6. Bacterial infection related pathways. Our genomic data suggests a potential role for SPHK2 in PA-induced pneumonia through elevated expression of inflammatory genes in lung tissue. Further, validation by RT-PCR on 10 differentially expressed genes showed 100% concordance in terms of vectoral changes as well as significant fold change. CONCLUSION: Using Sphk2(−/−) mice and differential gene expression analysis, we have shown here that S1P/SPHK2 signaling could play a key role in promoting PA pneumonia. The identified genes promote inflammation and suppress others that naturally inhibit inflammation and host defense. Thus, targeting SPHK2/S1P signaling in PA-induced lung inflammation could serve as a potential therapy to combat PA-induced pneumonia.",2019 Dec 16,"['Ebenezer, David L.', 'Fu, Panfeng', 'Krishnan, Yashaswin', 'Maienschein-Cline, Mark', 'Hu, Hong', 'Jung, Segun', 'Madduri, Ravi', 'Arbieva, Zarema', 'Harijith, Anantha', 'Natarajan, Viswanathan']",BMC Genomics,,,True
1d105041da2d3a6e6e16cd0dce1f0a672066d407,PMC,Development of an Immunochromatographic Strip for Rapid Detection of Canine Adenovirus,http://dx.doi.org/10.3389/fmicb.2019.02882,PMC6917642,31921060,CC BY,"Although canine adenovirus (CAdV) is highly prevalent in dogs, there is currently a lack of a quick diagnostic method. In this study, we developed a rapid immunochromatographic strip (ICS) assay using colloidal gold coupled to CAdV-2-specific monoclonal antibodies (mAbs). BALB/c mice were immunized with a purified CAdV-2 suspension, and four mAbs (belonging to two different epitopes) were generated and designated as 2C1, 7D7, 10D1, and 4G1. Western blot and protein spectral analysis indicated that the hexon protein of CAdV-2 recognized all four mAbs. The colloidal gold-coupled 7D7 and 2C1 mAbs were chosen for inclusion in the rapid ICS assay. The optimal concentrations of the coating antibody (2C1), the capture antibody (7D7), and the goat anti-mouse antibody were 1.0 mg/ml, 10 μg/ml, and 2.0 mg/ml, respectively. The limit of detection was approximately 2.0 × 10(2) tissue culture infective dose (TCID(50))/ml. Other common canine viruses were tested to evaluate the specificity of the ICS, and positive results were observed for only CAdV-1 and CAdV-2. The ICS test was conducted on 360 samples to detect CAdV, and the results were compared with those of polymerase chain reaction (PCR) tests. The ICS test was found to be a sufficiently sensitive and specific detection method for the convenient and rapid detection of CAdV.",2019 Dec 11,"['Wang, Shujie', 'Wen, Yongjun', 'An, Tongqing', 'Duan, Guixin', 'Sun, MingXia', 'Ge, Jinying', 'Li, Xi', 'Yang, Kongbin', 'Cai, Xuehui']",Front Microbiol,,,True
9235abaf9b34976f68a8d0031a94201fe371d364,PMC,SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection,http://dx.doi.org/10.1038/s41467-019-13659-4,PMC6920372,31852899,CC BY,"Autophagy is an essential cellular process affecting virus infections and other diseases and Beclin1 (BECN1) is one of its key regulators. Here, we identified S-phase kinase-associated protein 2 (SKP2) as E3 ligase that executes lysine-48-linked poly-ubiquitination of BECN1, thus promoting its proteasomal degradation. SKP2 activity is regulated by phosphorylation in a hetero-complex involving FKBP51, PHLPP, AKT1, and BECN1. Genetic or pharmacological inhibition of SKP2 decreases BECN1 ubiquitination, decreases BECN1 degradation and enhances autophagic flux. Middle East respiratory syndrome coronavirus (MERS-CoV) multiplication results in reduced BECN1 levels and blocks the fusion of autophagosomes and lysosomes. Inhibitors of SKP2 not only enhance autophagy but also reduce the replication of MERS-CoV up to 28,000-fold. The SKP2-BECN1 link constitutes a promising target for host-directed antiviral drugs and possibly other autophagy-sensitive conditions.",2019 Dec 18,"['Gassen, Nils C.', 'Niemeyer, Daniela', 'Muth, Doreen', 'Corman, Victor M.', 'Martinelli, Silvia', 'Gassen, Alwine', 'Hafner, Kathrin', 'Papies, Jan', 'Mösbauer, Kirstin', 'Zellner, Andreas', 'Zannas, Anthony S.', 'Herrmann, Alexander', 'Holsboer, Florian', 'Brack-Werner, Ruth', 'Boshart, Michael', 'Müller-Myhsok, Bertram', 'Drosten, Christian', 'Müller, Marcel A.', 'Rein, Theo']",Nat Commun,,,True
0a0afb5dc02afa81689e0e75afe2f9a21ce09e70,PMC,SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection,http://dx.doi.org/10.1038/s41467-019-13659-4,PMC6920372,31852899,CC BY,"Autophagy is an essential cellular process affecting virus infections and other diseases and Beclin1 (BECN1) is one of its key regulators. Here, we identified S-phase kinase-associated protein 2 (SKP2) as E3 ligase that executes lysine-48-linked poly-ubiquitination of BECN1, thus promoting its proteasomal degradation. SKP2 activity is regulated by phosphorylation in a hetero-complex involving FKBP51, PHLPP, AKT1, and BECN1. Genetic or pharmacological inhibition of SKP2 decreases BECN1 ubiquitination, decreases BECN1 degradation and enhances autophagic flux. Middle East respiratory syndrome coronavirus (MERS-CoV) multiplication results in reduced BECN1 levels and blocks the fusion of autophagosomes and lysosomes. Inhibitors of SKP2 not only enhance autophagy but also reduce the replication of MERS-CoV up to 28,000-fold. The SKP2-BECN1 link constitutes a promising target for host-directed antiviral drugs and possibly other autophagy-sensitive conditions.",2019 Dec 18,"['Gassen, Nils C.', 'Niemeyer, Daniela', 'Muth, Doreen', 'Corman, Victor M.', 'Martinelli, Silvia', 'Gassen, Alwine', 'Hafner, Kathrin', 'Papies, Jan', 'Mösbauer, Kirstin', 'Zellner, Andreas', 'Zannas, Anthony S.', 'Herrmann, Alexander', 'Holsboer, Florian', 'Brack-Werner, Ruth', 'Boshart, Michael', 'Müller-Myhsok, Bertram', 'Drosten, Christian', 'Müller, Marcel A.', 'Rein, Theo']",Nat Commun,,,True
d91a90b50edf1fa3390f2b7dedc5284bc7936170,PMC,SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection,http://dx.doi.org/10.1038/s41467-019-13659-4,PMC6920372,31852899,CC BY,"Autophagy is an essential cellular process affecting virus infections and other diseases and Beclin1 (BECN1) is one of its key regulators. Here, we identified S-phase kinase-associated protein 2 (SKP2) as E3 ligase that executes lysine-48-linked poly-ubiquitination of BECN1, thus promoting its proteasomal degradation. SKP2 activity is regulated by phosphorylation in a hetero-complex involving FKBP51, PHLPP, AKT1, and BECN1. Genetic or pharmacological inhibition of SKP2 decreases BECN1 ubiquitination, decreases BECN1 degradation and enhances autophagic flux. Middle East respiratory syndrome coronavirus (MERS-CoV) multiplication results in reduced BECN1 levels and blocks the fusion of autophagosomes and lysosomes. Inhibitors of SKP2 not only enhance autophagy but also reduce the replication of MERS-CoV up to 28,000-fold. The SKP2-BECN1 link constitutes a promising target for host-directed antiviral drugs and possibly other autophagy-sensitive conditions.",2019 Dec 18,"['Gassen, Nils C.', 'Niemeyer, Daniela', 'Muth, Doreen', 'Corman, Victor M.', 'Martinelli, Silvia', 'Gassen, Alwine', 'Hafner, Kathrin', 'Papies, Jan', 'Mösbauer, Kirstin', 'Zellner, Andreas', 'Zannas, Anthony S.', 'Herrmann, Alexander', 'Holsboer, Florian', 'Brack-Werner, Ruth', 'Boshart, Michael', 'Müller-Myhsok, Bertram', 'Drosten, Christian', 'Müller, Marcel A.', 'Rein, Theo']",Nat Commun,,,False
3012e3f833915e67993777c3a69d90013bff8c1e,PMC,SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection,http://dx.doi.org/10.1038/s41467-019-13659-4,PMC6920372,31852899,CC BY,"Autophagy is an essential cellular process affecting virus infections and other diseases and Beclin1 (BECN1) is one of its key regulators. Here, we identified S-phase kinase-associated protein 2 (SKP2) as E3 ligase that executes lysine-48-linked poly-ubiquitination of BECN1, thus promoting its proteasomal degradation. SKP2 activity is regulated by phosphorylation in a hetero-complex involving FKBP51, PHLPP, AKT1, and BECN1. Genetic or pharmacological inhibition of SKP2 decreases BECN1 ubiquitination, decreases BECN1 degradation and enhances autophagic flux. Middle East respiratory syndrome coronavirus (MERS-CoV) multiplication results in reduced BECN1 levels and blocks the fusion of autophagosomes and lysosomes. Inhibitors of SKP2 not only enhance autophagy but also reduce the replication of MERS-CoV up to 28,000-fold. The SKP2-BECN1 link constitutes a promising target for host-directed antiviral drugs and possibly other autophagy-sensitive conditions.",2019 Dec 18,"['Gassen, Nils C.', 'Niemeyer, Daniela', 'Muth, Doreen', 'Corman, Victor M.', 'Martinelli, Silvia', 'Gassen, Alwine', 'Hafner, Kathrin', 'Papies, Jan', 'Mösbauer, Kirstin', 'Zellner, Andreas', 'Zannas, Anthony S.', 'Herrmann, Alexander', 'Holsboer, Florian', 'Brack-Werner, Ruth', 'Boshart, Michael', 'Müller-Myhsok, Bertram', 'Drosten, Christian', 'Müller, Marcel A.', 'Rein, Theo']",Nat Commun,,,True
c1e2ffff403bab75c973812b3bf2e8d5a2f07600,PMC,Human core duplicon gene families: game changers or game players?,http://dx.doi.org/10.1093/bfgp/elz016,PMC6920530,31529038,CC BY,"Illuminating the role of specific gene duplications within the human lineage can provide insights into human-specific adaptations. The so-called human core duplicon gene families have received particular attention in this respect, due to special features, such as expansion along single chromosomes, newly acquired protein domains and signatures of positive selection. Here, we summarize the data available for 10 such families and include some new analyses. A picture emerges that suggests broad functions for these protein families, possibly through modification of core cellular pathways. Still, more dedicated studies are required to elucidate the function of core-duplicons gene families and how they have shaped adaptations and evolution of humans.",2019 Sep 16,"['Bekpen, Cemalettin', 'Tautz, Diethard']",Brief Funct Genomics,,,True
da6eca2ce0887d1ac0cf592d964a42717bcaa33b,PMC,Are Community Acquired Respiratory Viral Infections an Underestimated Burden in Hematology Patients?,http://dx.doi.org/10.3390/microorganisms7110521,PMC6920795,31684063,CC BY,"Despite a plethora of studies demonstrating significant morbidity and mortality due to community-acquired respiratory viral (CRV) infections in intensively treated hematology patients, and despite the availability of evidence-based guidelines for the diagnosis and management of respiratory viral infections in this setting, there is no uniform inclusion of respiratory viral infection management in the clinical hematology routine. Nevertheless, timely diagnosis and systematic management of CRV infections in intensively treated hematology patients has a demonstrated potential to significantly improve outcome. We have briefly summarized the recently published data on CRV infection epidemiology, as well as guidelines on the diagnosis and management of CRV infections in patients intensively treated for hematological malignancies. We have also assessed available treatment options, as well as mentioned novel agents currently in development.",2019 Nov 2,"['Popescu, Cristian-Marian', 'Ursache, Aurora Livia', 'Feketea, Gavriela', 'Bocsan, Corina', 'Jimbu, Laura', 'Mesaros, Oana', 'Edwards, Michael', 'Wang, Hongwei', 'Berceanu, Iulia', 'Neaga, Alexandra', 'Zdrenghea, Mihnea']",Microorganisms,,,True
ba29366173f97f54a22e5c410b3d05e9a9649d28,PMC,Foodborne Transmission of Deformed Wing Virus to Ants (Myrmica rubra),http://dx.doi.org/10.3390/insects10110394,PMC6920936,31703426,CC BY,"Virus host shifts occur frequently, but the whole range of host species and the actual transmission pathways are often poorly understood. Deformed wing virus (DWV), an RNA virus described from honeybees (Apis mellifera), has been shown to have a broad host range. Since ants are often scavenging on dead honeybees, foodborne transmission of these viruses may occur. However, the role of the ant Myrmica rubra as an alternative host is not known and foodborne transmission to ants has not been experimentally addressed yet. Here, we show with a 16-week feeding experiment that foodborne transmission enables DWV type-A and -B to infect M. rubra and that these ants may serve as a virus reservoir. However, the titers of both plus- and minus-sense viral RNA strands decreased over time. Since the ants were fed with highly virus-saturated honeybee pupae, this probably resulted in initial viral peaks, then approaching lower equilibrium titers in infected individuals later. Since DWV infections were also found in untreated field-collected M. rubra colonies, our results support the wide host range of DWV and further suggest foodborne transmission as a so far underestimated spread mechanism.",2019 Nov 7,"['Schläppi, Daniel', 'Lattrell, Patrick', 'Yañez, Orlando', 'Chejanovsky, Nor', 'Neumann, Peter']",Insects,,,True
8ff8f6e5389f4474c5035cd105310a75e6c6e9a1,PMC,Foodborne Transmission of Deformed Wing Virus to Ants (Myrmica rubra),http://dx.doi.org/10.3390/insects10110394,PMC6920936,31703426,CC BY,"Virus host shifts occur frequently, but the whole range of host species and the actual transmission pathways are often poorly understood. Deformed wing virus (DWV), an RNA virus described from honeybees (Apis mellifera), has been shown to have a broad host range. Since ants are often scavenging on dead honeybees, foodborne transmission of these viruses may occur. However, the role of the ant Myrmica rubra as an alternative host is not known and foodborne transmission to ants has not been experimentally addressed yet. Here, we show with a 16-week feeding experiment that foodborne transmission enables DWV type-A and -B to infect M. rubra and that these ants may serve as a virus reservoir. However, the titers of both plus- and minus-sense viral RNA strands decreased over time. Since the ants were fed with highly virus-saturated honeybee pupae, this probably resulted in initial viral peaks, then approaching lower equilibrium titers in infected individuals later. Since DWV infections were also found in untreated field-collected M. rubra colonies, our results support the wide host range of DWV and further suggest foodborne transmission as a so far underestimated spread mechanism.",2019 Nov 7,"['Schläppi, Daniel', 'Lattrell, Patrick', 'Yañez, Orlando', 'Chejanovsky, Nor', 'Neumann, Peter']",Insects,,,False
c60392b55a9acde4311257b1693ce0285a922aae,PMC,Zika and Flavivirus Shell Disorder: Virulence and Fetal Morbidity,http://dx.doi.org/10.3390/biom9110710,PMC6920988,31698857,CC BY,"Zika virus (ZIKV) was first discovered in 1947 in Africa. Since then, sporadic ZIKV infections of humans have been reported in Africa and Asia. For a long time, this virus was mostly unnoticed due to its mild symptoms and low fatality rates. However, during the 2015–2016 epidemic in Central and South America, when millions of people were infected, it was discovered that ZIKV causes microcephaly in the babies of mothers infected during pregnancy. An examination of the M and C proteins of the ZIKV shell using the disorder predictor PONDR VLXT revealed that the M protein contains relatively high disorder levels comparable only to those of the yellow fever virus (YFV). On the other hand, the disorder levels in the C protein are relatively low, which can account for the low case fatality rate (CFR) of this virus in contrast to the more virulent YFV, which is characterized by high disorder in its C protein. A larger variation was found in the percentage of intrinsic disorder (PID) in the C protein of various ZIKV strains. Strains of African lineage are characterized by higher PIDs. Using both in vivo and in vitro experiments, laboratories have also previously shown that strains of African origin have a greater potential to inflict higher fetal morbidity than do strains of Asian lineage, with dengue-2 virus (DENV-2) having the least potential. Strong correlations were found between the potential to inflict fetal morbidity and shell disorder in ZIKV (r(2) = 0.9) and DENV-2 (DENV-2 + ZIKV, r(2) = 0.8). A strong correlation between CFR and PID was also observed when ZIKV was included in an analysis of sets of shell proteins from a variety of flaviviruses (r(2) = 0.8). These observations have potential implications for antiviral vaccine development and for the design of cancer therapeutics in terms of developing therapeutic viruses that penetrate hard-to-reach organs.",2019 Nov 6,"['Goh, Gerard Kian-Meng', 'Dunker, A. Keith', 'Foster, James A.', 'Uversky, Vladimir N.']",Biomolecules,,,True
9dcd0de611607a2ffb8c1fc1ef4a521e05efc35f,PMC,Zika and Flavivirus Shell Disorder: Virulence and Fetal Morbidity,http://dx.doi.org/10.3390/biom9110710,PMC6920988,31698857,CC BY,"Zika virus (ZIKV) was first discovered in 1947 in Africa. Since then, sporadic ZIKV infections of humans have been reported in Africa and Asia. For a long time, this virus was mostly unnoticed due to its mild symptoms and low fatality rates. However, during the 2015–2016 epidemic in Central and South America, when millions of people were infected, it was discovered that ZIKV causes microcephaly in the babies of mothers infected during pregnancy. An examination of the M and C proteins of the ZIKV shell using the disorder predictor PONDR VLXT revealed that the M protein contains relatively high disorder levels comparable only to those of the yellow fever virus (YFV). On the other hand, the disorder levels in the C protein are relatively low, which can account for the low case fatality rate (CFR) of this virus in contrast to the more virulent YFV, which is characterized by high disorder in its C protein. A larger variation was found in the percentage of intrinsic disorder (PID) in the C protein of various ZIKV strains. Strains of African lineage are characterized by higher PIDs. Using both in vivo and in vitro experiments, laboratories have also previously shown that strains of African origin have a greater potential to inflict higher fetal morbidity than do strains of Asian lineage, with dengue-2 virus (DENV-2) having the least potential. Strong correlations were found between the potential to inflict fetal morbidity and shell disorder in ZIKV (r(2) = 0.9) and DENV-2 (DENV-2 + ZIKV, r(2) = 0.8). A strong correlation between CFR and PID was also observed when ZIKV was included in an analysis of sets of shell proteins from a variety of flaviviruses (r(2) = 0.8). These observations have potential implications for antiviral vaccine development and for the design of cancer therapeutics in terms of developing therapeutic viruses that penetrate hard-to-reach organs.",2019 Nov 6,"['Goh, Gerard Kian-Meng', 'Dunker, A. Keith', 'Foster, James A.', 'Uversky, Vladimir N.']",Biomolecules,,,False
168ee484462356a280cd7fe162b1b7a8d81e80c5,PMC,"Natural Bis-Benzylisoquinoline Alkaloids-Tetrandrine, Fangchinoline, and Cepharanthine, Inhibit Human Coronavirus OC43 Infection of MRC-5 Human Lung Cells",http://dx.doi.org/10.3390/biom9110696,PMC6921063,31690059,CC BY,"Stephania tetrandra and other related species of Menispermaceae are the major sources of the bis-benzylisoquinoline alkaloids tetrandrine (TET), fangchinoline (FAN), and cepharanthine (CEP). Although the pharmacological properties of these compounds include anticancer and anti-inflammatory activities, the antiviral effects of these compounds against human coronavirus (HCoV) remain unclear. Hence, the aims of the current study were to assess the antiviral activities of TET, FAN, and CEP and to elucidate the underlying mechanisms in HCoV-OC43-infected MRC-5 human lung cells. These compounds significantly inhibited virus-induced cell death at the early stage of virus infection. TET, FAN, and CEP treatment dramatically suppressed the replication of HCoV-OC43 as well as inhibited viral S and N protein expression. The virus-induced host response was reduced by compound treatment as compared with the vehicle control. Taken together, these findings demonstrate that TET, FAN, and CEP are potential natural antiviral agents for the prevention and treatment of HCoV-OC43 infection.",2019 Nov 4,"['Kim, Dong Eon', 'Min, Jung Sun', 'Jang, Min Seong', 'Lee, Jun Young', 'Shin, Young Sup', 'Park, Chul Min', 'Song, Jong Hwan', 'Kim, Hyoung Rae', 'Kim, Seungtaek', 'Jin, Young-Hee', 'Kwon, Sunoh']",Biomolecules,,,True
8eb3bdc336b90a70201e28477934062f67afcbcf,PMC,When could human challenge trials be deployed to combat emerging infectious diseases? Lessons from the case of a Zika virus human challenge trial,http://dx.doi.org/10.1186/s13063-019-3843-0,PMC6921433,31852506,CC BY,"Human challenge trials (HCTs) deliberately infect participants in order to test vaccines and treatments in a controlled setting, rather than enrolling individuals with natural exposure to a disease. HCTs are therefore potentially powerful tools to prepare for future outbreaks of emerging infectious diseases. Yet when an infectious disease is emerging, there is often substantial risk and uncertainty about its complications, and few available interventions, making an HCT ethically complex. In light of the need to consider ethical issues proactively as a part of epidemic preparedness, we use the case of a Zika virus HCT to explore whether and when HCTs might be ethically justified to combat emerging infectious diseases. We conclude that emerging infectious diseases could be appropriate candidates for HCTs and we identify relevant considerations and provide a case example to illustrate when they might be ethically acceptable.",2019 Dec 19,"['Palacios, Ricardo', 'Shah, Seema K.']",Trials,,,True
9a8ffdaee3a800f0e6867b63ffd109e9c30621b8,PMC,Efficacy of glucocorticoids for the treatment of macrolide refractory mycoplasma pneumonia in children: meta-analysis of randomized controlled trials,http://dx.doi.org/10.1186/s12890-019-0990-8,PMC6921474,31852460,CC BY,"BACKGROUND: Mycoplasma pneumoniae is one of the most common pathogens causing community acquired pneumonia in children. Although the rate of macrolide-refractory Mycoplasma pneumoniae (MRMP) has increased, systemic glucocorticoids as a treatment option has not been validated yet. The purpose of this study was to assess the efficacy of glucocorticoids add-on in the treatment of MRMP in children through systematic review and meta-analysis. METHODS: Data sources A systematic literature search was conducted using ten electronic bibliographic databases including English, Korean, Chinese and Japanese languages, up to March 8, 2018. Study selection The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and selected randomized control trials which compared the efficacy of glucocorticoids add-on to macrolide in the treatment of MRMP in children. Data extraction Two independent reviewers extracted: primary outcomes as hospital days, fever duration, and change in C-reactive protein (CRP) and main analysis was performed through meta-analysis with random effects model. RESULTS: Twenty-four unique randomized controlled trials met the inclusion criteria. The mean length of hospital stay in glucocorticoids treatment group was significantly shorter than that in conventional macrolide-treatment group (Weighted mean difference (WMD) = − 4.03 days). The mean length of fever duration was significantly shorter in the glucocorticoid treatment group in comparison with the conventional treatment group (WMD = -3.32 days). Level of CRP after treatment was significantly lower in the glucocorticoid treatment group than that in the conventional treatment group (WMD = -16.03). Sensitivity analysis and subgroup analysis showed no significant improvement in heterogeneity. As limitations of the study, most of the studies included were from a single country and we were unable to control for heterogeneity across interventions, lack of standardized measures, and different time points of assessments across studies. CONCLUSIONS: Glucocorticoid add-on treatment for MRMP can significantly shorten the duration of fever and hospital stay and decrease the level of CRP. These results should be confirmed by adequately powered studies in the future.",2019 Dec 18,"['Kim, Hwan Soo', 'Sol, In Suk', 'Li, Donghe', 'Choi, Miyoung', 'Choi, Yun Jung', 'Lee, Kyung Suk', 'Seo, Ju Hee', 'Lee, Yong Ju', 'Yang, Hyeon-Jong', 'Kim, Hyun Hee']",BMC Pulm Med,,,True
d3f515c47fec377ecc7f3961948916239e4e079f,PMC,Epstein-Barr Virus Nuclear Antigen 1 Recruits Cyclophilin A to Facilitate the Replication of Viral DNA Genome,http://dx.doi.org/10.3389/fmicb.2019.02879,PMC6923202,31921057,CC BY,"Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1)-mediated DNA episomal genome replication and persistence are essential for the viral pathogenesis. Cyclophilin A (CYPA) is upregulated in EBV-associated nasopharyngeal carcinoma (NPC) with unknown roles. In the present approach, cytosolic CYPA was found to be bound with EBNA1 into the nucleus. The amino acid 376-459 of the EBNA1 domain was important for the binding. CYPA depletion attenuated and ectopic CYPA expression improved EBNA1 expression in EBV-positive cells. The loss of viral copy number was also accelerated by CYPA consumption in daughter cells during culture passages. Mechanistically, CYPA mediated the connection of EBNA1 with oriP (origin of EBV DNA replication) and subsequent oriP transcription, which is a key step for the initiation of EBV genome replication. Moreover, CYPA overexpression markedly antagonized the connection of EBNA1 to Ubiquitin-specific protease 7 (USP7), which is a strong host barrier with a role of inhibiting EBV genome replication. The PPIase activity of CYPA was required for the promotion of oriP transcription and antagonism with USP7. The results revealed a strategy that EBV recruited a host factor to counteract the host defense, thus facilitating its own latent genome replication. This study provides a new insight into EBV pathogenesis and potential virus-targeted therapeutics in EBV-associated NPC, in which CYPA is upregulated at all stages.",2019 Dec 13,"['Xin, Shuyu', 'Du, Shujuan', 'Liu, Lingzhi', 'Xie, Yan', 'Zuo, Lielian', 'Yang, Jing', 'Hu, Jingjin', 'Yue, Wenxing', 'Zhang, Jing', 'Cao, Pengfei', 'Zhu, Fanxiu', 'Lu, Jianhong']",Front Microbiol,,,True
fed2868ea613384ac2cd9744c614a6d8170f0fe0,PMC,Epstein-Barr Virus Nuclear Antigen 1 Recruits Cyclophilin A to Facilitate the Replication of Viral DNA Genome,http://dx.doi.org/10.3389/fmicb.2019.02879,PMC6923202,31921057,CC BY,"Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1)-mediated DNA episomal genome replication and persistence are essential for the viral pathogenesis. Cyclophilin A (CYPA) is upregulated in EBV-associated nasopharyngeal carcinoma (NPC) with unknown roles. In the present approach, cytosolic CYPA was found to be bound with EBNA1 into the nucleus. The amino acid 376-459 of the EBNA1 domain was important for the binding. CYPA depletion attenuated and ectopic CYPA expression improved EBNA1 expression in EBV-positive cells. The loss of viral copy number was also accelerated by CYPA consumption in daughter cells during culture passages. Mechanistically, CYPA mediated the connection of EBNA1 with oriP (origin of EBV DNA replication) and subsequent oriP transcription, which is a key step for the initiation of EBV genome replication. Moreover, CYPA overexpression markedly antagonized the connection of EBNA1 to Ubiquitin-specific protease 7 (USP7), which is a strong host barrier with a role of inhibiting EBV genome replication. The PPIase activity of CYPA was required for the promotion of oriP transcription and antagonism with USP7. The results revealed a strategy that EBV recruited a host factor to counteract the host defense, thus facilitating its own latent genome replication. This study provides a new insight into EBV pathogenesis and potential virus-targeted therapeutics in EBV-associated NPC, in which CYPA is upregulated at all stages.",2019 Dec 13,"['Xin, Shuyu', 'Du, Shujuan', 'Liu, Lingzhi', 'Xie, Yan', 'Zuo, Lielian', 'Yang, Jing', 'Hu, Jingjin', 'Yue, Wenxing', 'Zhang, Jing', 'Cao, Pengfei', 'Zhu, Fanxiu', 'Lu, Jianhong']",Front Microbiol,,,False
4cbebfa064d2b234ab25b2a1d0ffaf97739bcb04,PMC,"Effects of the Toll-like receptor 7 (TLR7) agonist, AZD8848, on allergen-induced responses in patients with mild asthma: a double-blind, randomised, parallel-group study",http://dx.doi.org/10.1186/s12931-019-1252-2,PMC6924002,31856838,CC BY,"BACKGROUND: Although allergic asthma is a complex area with many interacting factors involved, the ‘hygiene hypothesis’ proposes that a lack of exposure to infection during childhood may polarise the immune system towards allergen-reactive Th2-type responses in genetically susceptible individuals. Toll-like receptors (TLRs) play a key role within the innate immune system and TLR7 agonists have previously been shown to up-regulate Th1 responses and down-regulate Th2 responses to allergens in murine models of allergic or chronic asthma. This study aimed to examine the efficacy and safety of the novel TRL7 agonist AZD8848, which has been developed as an antedrug. METHODS: In this double-blind, randomised, parallel-group study, AZD8848 60 μg or placebo was administered intranasally once-weekly for 8 weeks in patients with mild-to-moderate allergic asthma (NCT00999466). Efficacy assessments were performed at 1 and 4 weeks after the last dose. The primary outcome was the late asthmatic response (LAR) fall in forced expiratory volume in 1 s (FEV(1)) after allergen challenge at 1-week post-treatment. RESULTS: AZD8848 significantly reduced average LAR fall in FEV(1) by 27% vs. placebo at 1 week after treatment (p = 0.035). This effect was sustained at 4 weeks post-treatment; however, it did not reach clinical significance. AZD8848 reduced post-allergen challenge methacholine-induced airway hyper-responsiveness (AHR) vs. placebo at 1 week post-dosing (treatment ratio: 2.20, p = 0.024), with no effect at 4 weeks. There was no significant difference between the two groups in plasma cytokine, sputum Th2 cytokine or eosinophil responses post-allergen challenge at 1 week after treatment. The incidence of adverse events was similar in the two groups. AZD8848 was generally well tolerated. CONCLUSIONS AND CLINICAL RELEVANCE: In patients with allergic asthma, TLR7 agonists could potentially reduce allergen responsiveness by stimulating Type 1 interferon responses to down-regulate the dominant Th2 responses. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT00999466.",2019 Dec 19,"['Leaker, Brian R.', 'Singh, Dave', 'Lindgren, Sam', 'Almqvist, Gun', 'Eriksson, Leif', 'Young, Barbara', 'O’Connor, Brian']",Respir Res,,,True
7e157857bd700d014c57fdc0f4d4f9dcb4b3d3f6,PMC,Prediction of novel mouse TLR9 agonists using a random forest approach,http://dx.doi.org/10.1186/s12860-019-0241-0,PMC6924143,31856726,CC BY,"BACKGROUND: Toll-like receptor 9 is a key innate immune receptor involved in detecting infectious diseases and cancer. TLR9 activates the innate immune system following the recognition of single-stranded DNA oligonucleotides (ODN) containing unmethylated cytosine-guanine (CpG) motifs. Due to the considerable number of rotatable bonds in ODNs, high-throughput in silico screening for potential TLR9 activity via traditional structure-based virtual screening approaches of CpG ODNs is challenging. In the current study, we present a machine learning based method for predicting novel mouse TLR9 (mTLR9) agonists based on features including count and position of motifs, the distance between the motifs and graphically derived features such as the radius of gyration and moment of Inertia. We employed an in-house experimentally validated dataset of 396 single-stranded synthetic ODNs, to compare the results of five machine learning algorithms. Since the dataset was highly imbalanced, we used an ensemble learning approach based on repeated random down-sampling. RESULTS: Using in-house experimental TLR9 activity data we found that random forest algorithm outperformed other algorithms for our dataset for TLR9 activity prediction. Therefore, we developed a cross-validated ensemble classifier of 20 random forest models. The average Matthews correlation coefficient and balanced accuracy of our ensemble classifier in test samples was 0.61 and 80.0%, respectively, with the maximum balanced accuracy and Matthews correlation coefficient of 87.0% and 0.75, respectively. We confirmed common sequence motifs including ‘CC’, ‘GG’,‘AG’, ‘CCCG’ and ‘CGGC’ were overrepresented in mTLR9 agonists. Predictions on 6000 randomly generated ODNs were ranked and the top 100 ODNs were synthesized and experimentally tested for activity in a mTLR9 reporter cell assay, with 91 of the 100 selected ODNs showing high activity, confirming the accuracy of the model in predicting mTLR9 activity. CONCLUSION: We combined repeated random down-sampling with random forest to overcome the class imbalance problem and achieved promising results. Overall, we showed that the random forest algorithm outperformed other machine learning algorithms including support vector machines, shrinkage discriminant analysis, gradient boosting machine and neural networks. Due to its predictive performance and simplicity, the random forest technique is a useful method for prediction of mTLR9 ODN agonists.",2019 Dec 20,"['Khanna, Varun', 'Li, Lei', 'Fung, Johnson', 'Ranganathan, Shoba', 'Petrovsky, Nikolai']",BMC Mol Cell Biol,,,False
14356aa23488185481c44d9b60c17afe86d30f29,PMC,Prediction of novel mouse TLR9 agonists using a random forest approach,http://dx.doi.org/10.1186/s12860-019-0241-0,PMC6924143,31856726,CC BY,"BACKGROUND: Toll-like receptor 9 is a key innate immune receptor involved in detecting infectious diseases and cancer. TLR9 activates the innate immune system following the recognition of single-stranded DNA oligonucleotides (ODN) containing unmethylated cytosine-guanine (CpG) motifs. Due to the considerable number of rotatable bonds in ODNs, high-throughput in silico screening for potential TLR9 activity via traditional structure-based virtual screening approaches of CpG ODNs is challenging. In the current study, we present a machine learning based method for predicting novel mouse TLR9 (mTLR9) agonists based on features including count and position of motifs, the distance between the motifs and graphically derived features such as the radius of gyration and moment of Inertia. We employed an in-house experimentally validated dataset of 396 single-stranded synthetic ODNs, to compare the results of five machine learning algorithms. Since the dataset was highly imbalanced, we used an ensemble learning approach based on repeated random down-sampling. RESULTS: Using in-house experimental TLR9 activity data we found that random forest algorithm outperformed other algorithms for our dataset for TLR9 activity prediction. Therefore, we developed a cross-validated ensemble classifier of 20 random forest models. The average Matthews correlation coefficient and balanced accuracy of our ensemble classifier in test samples was 0.61 and 80.0%, respectively, with the maximum balanced accuracy and Matthews correlation coefficient of 87.0% and 0.75, respectively. We confirmed common sequence motifs including ‘CC’, ‘GG’,‘AG’, ‘CCCG’ and ‘CGGC’ were overrepresented in mTLR9 agonists. Predictions on 6000 randomly generated ODNs were ranked and the top 100 ODNs were synthesized and experimentally tested for activity in a mTLR9 reporter cell assay, with 91 of the 100 selected ODNs showing high activity, confirming the accuracy of the model in predicting mTLR9 activity. CONCLUSION: We combined repeated random down-sampling with random forest to overcome the class imbalance problem and achieved promising results. Overall, we showed that the random forest algorithm outperformed other machine learning algorithms including support vector machines, shrinkage discriminant analysis, gradient boosting machine and neural networks. Due to its predictive performance and simplicity, the random forest technique is a useful method for prediction of mTLR9 ODN agonists.",2019 Dec 20,"['Khanna, Varun', 'Li, Lei', 'Fung, Johnson', 'Ranganathan, Shoba', 'Petrovsky, Nikolai']",BMC Mol Cell Biol,,,False
1530303b9363084dc4a77eef5a36ab160a66148e,PMC,Prediction of novel mouse TLR9 agonists using a random forest approach,http://dx.doi.org/10.1186/s12860-019-0241-0,PMC6924143,31856726,CC BY,"BACKGROUND: Toll-like receptor 9 is a key innate immune receptor involved in detecting infectious diseases and cancer. TLR9 activates the innate immune system following the recognition of single-stranded DNA oligonucleotides (ODN) containing unmethylated cytosine-guanine (CpG) motifs. Due to the considerable number of rotatable bonds in ODNs, high-throughput in silico screening for potential TLR9 activity via traditional structure-based virtual screening approaches of CpG ODNs is challenging. In the current study, we present a machine learning based method for predicting novel mouse TLR9 (mTLR9) agonists based on features including count and position of motifs, the distance between the motifs and graphically derived features such as the radius of gyration and moment of Inertia. We employed an in-house experimentally validated dataset of 396 single-stranded synthetic ODNs, to compare the results of five machine learning algorithms. Since the dataset was highly imbalanced, we used an ensemble learning approach based on repeated random down-sampling. RESULTS: Using in-house experimental TLR9 activity data we found that random forest algorithm outperformed other algorithms for our dataset for TLR9 activity prediction. Therefore, we developed a cross-validated ensemble classifier of 20 random forest models. The average Matthews correlation coefficient and balanced accuracy of our ensemble classifier in test samples was 0.61 and 80.0%, respectively, with the maximum balanced accuracy and Matthews correlation coefficient of 87.0% and 0.75, respectively. We confirmed common sequence motifs including ‘CC’, ‘GG’,‘AG’, ‘CCCG’ and ‘CGGC’ were overrepresented in mTLR9 agonists. Predictions on 6000 randomly generated ODNs were ranked and the top 100 ODNs were synthesized and experimentally tested for activity in a mTLR9 reporter cell assay, with 91 of the 100 selected ODNs showing high activity, confirming the accuracy of the model in predicting mTLR9 activity. CONCLUSION: We combined repeated random down-sampling with random forest to overcome the class imbalance problem and achieved promising results. Overall, we showed that the random forest algorithm outperformed other machine learning algorithms including support vector machines, shrinkage discriminant analysis, gradient boosting machine and neural networks. Due to its predictive performance and simplicity, the random forest technique is a useful method for prediction of mTLR9 ODN agonists.",2019 Dec 20,"['Khanna, Varun', 'Li, Lei', 'Fung, Johnson', 'Ranganathan, Shoba', 'Petrovsky, Nikolai']",BMC Mol Cell Biol,,,False
af987eff63f3d7ee36dc7631807d9aac7c165d2d,PMC,Prediction of novel mouse TLR9 agonists using a random forest approach,http://dx.doi.org/10.1186/s12860-019-0241-0,PMC6924143,31856726,CC BY,"BACKGROUND: Toll-like receptor 9 is a key innate immune receptor involved in detecting infectious diseases and cancer. TLR9 activates the innate immune system following the recognition of single-stranded DNA oligonucleotides (ODN) containing unmethylated cytosine-guanine (CpG) motifs. Due to the considerable number of rotatable bonds in ODNs, high-throughput in silico screening for potential TLR9 activity via traditional structure-based virtual screening approaches of CpG ODNs is challenging. In the current study, we present a machine learning based method for predicting novel mouse TLR9 (mTLR9) agonists based on features including count and position of motifs, the distance between the motifs and graphically derived features such as the radius of gyration and moment of Inertia. We employed an in-house experimentally validated dataset of 396 single-stranded synthetic ODNs, to compare the results of five machine learning algorithms. Since the dataset was highly imbalanced, we used an ensemble learning approach based on repeated random down-sampling. RESULTS: Using in-house experimental TLR9 activity data we found that random forest algorithm outperformed other algorithms for our dataset for TLR9 activity prediction. Therefore, we developed a cross-validated ensemble classifier of 20 random forest models. The average Matthews correlation coefficient and balanced accuracy of our ensemble classifier in test samples was 0.61 and 80.0%, respectively, with the maximum balanced accuracy and Matthews correlation coefficient of 87.0% and 0.75, respectively. We confirmed common sequence motifs including ‘CC’, ‘GG’,‘AG’, ‘CCCG’ and ‘CGGC’ were overrepresented in mTLR9 agonists. Predictions on 6000 randomly generated ODNs were ranked and the top 100 ODNs were synthesized and experimentally tested for activity in a mTLR9 reporter cell assay, with 91 of the 100 selected ODNs showing high activity, confirming the accuracy of the model in predicting mTLR9 activity. CONCLUSION: We combined repeated random down-sampling with random forest to overcome the class imbalance problem and achieved promising results. Overall, we showed that the random forest algorithm outperformed other machine learning algorithms including support vector machines, shrinkage discriminant analysis, gradient boosting machine and neural networks. Due to its predictive performance and simplicity, the random forest technique is a useful method for prediction of mTLR9 ODN agonists.",2019 Dec 20,"['Khanna, Varun', 'Li, Lei', 'Fung, Johnson', 'Ranganathan, Shoba', 'Petrovsky, Nikolai']",BMC Mol Cell Biol,,,True
437a7f66e0cb7f9fdf9d6b3ff4da80939e9ac546,PMC,"Seroprevalence and risk factors of bovine respiratory syncytial virus in cattle in the Nineveh Governorate, Iraq",http://dx.doi.org/10.14202/vetworld.2019.1862-1865,PMC6925036,32009767,CC BY,"BACKGROUND AND AIM: Bovine respiratory syncytial virus (BRSV) is one of the main causes of severe pneumonia, interstitial edema, and emphysema in cattle. The current study investigated the prevalence and risk factors of BRSV in cattle in the Nineveh Province, Iraq. MATERIALS AND METHODS: Between September 2017 and September 2018, 450 serum samples were collected from non-vaccinated cattle of different ages and breeds for BRSV testing. The epidemiological information of the animals was recorded. The prevalence of the disease was determined using an indirect enzyme-linked immunosorbent assay kit. RESULTS: The prevalence of BRSV was 83.11%, and it was significantly (p<0.05) higher in cattle aged greater than 7 months-1.5 years than in older animals; in imported cattle than in Native animals; and in animals originating from large herds (100 animals) than in those from smaller herds (40 animals). There was no significant difference between BRSV prevalence in male and female animals. When samples from different regions of the Nineveh Governorate were compared, the northern region was associated with the highest prevalence of the disease. Samples harvested in the winter displayed the highest BRSV titer, compared to those collected during the other seasons. CONCLUSION: BRSV is prevalent in cattle from the Nineveh Governorate. Risk factors such as animal age, origin, herd size, and the herd’s geographical location are associated with an increased prevalence of the disease in this region. Routine vaccination programs should be adopted to reduce the prevalence of BRSV.",2019 Nov 27,"['Hussain, Khder Jassiem', 'Al-Farwachi, Maab Ibrahim', 'Hassan, Sadam Dhahir']",Vet World,,,True
cc03e915afeb7acfe93595b75a38f7b58bf2d752,PMC,Isolation and characterization of avian coronavirus from healthy Eclectus parrots (Eclectus roratus) from Indonesia,http://dx.doi.org/10.14202/vetworld.2019.1797-1805,PMC6925039,32009759,CC BY,"BACKGROUND AND AIM: Avian coronavirus has a wide range of hosts, from chickens and turkeys to wild birds. This virus causes an economically and, possibly, environmentally, important loss in the poultry industry. Therefore, research into the avian coronavirus in various species of birds is required. The Eclectus parrot (Eclectus roratus) is an endemic bird to Indonesia and Northern Australia and often kept as pets. At present, there has been limited information about avian coronavirus infection among birds. This study aimed to determine the presence of and to characterize avian coronavirus isolated from Eclectus parrots in Indonesia. MATERIALS AND METHODS: Cloacal swab samples were taken from 10 healthy Eclectus parrots (E. roratus). Each isolate was propagated into specific pathogen-free embryonated chicken eggs. The presence of avian coronavirus was determined using three sets of primers targeting the 3’ untranslated region (3’-UTR) of avian coronavirus (UTR41+/11−), the N gene of the infectious bronchitis virus (IBVN+/−), and the S1 gene of the IBV (XCE2+/XCE2−). The infectious bronchitis vaccine strain H120 was used as a positive control. Resulting positive bands were sequenced for the S1 gene. RESULTS: None of the isolates was positive for the 3’-UTR, four isolates were positive for the N gene of infectious bronchitis, and two isolates were positive for the S1 gene of the IBV. However, only one isolate (parrot/Indonesia/BX9/16) was sequenced for the partial S1 gene with primers XCE2+/XCE2−. The partial nucleotide sequence of this isolate showed 100% homology with the IBV GI-13 lineage, specifically with a field isolate of the 4/91 variant 1 Israel and the 4/91 vaccine on the hypervariable region 3 site of the S1 gene. CONCLUSION: An IB-like avian coronavirus was isolated from healthy Eclectus parrots. Our results indicate that IBV has a wide range of hosts, which prompt the need to understand the interspecies connection of this virus better.",2019 Nov 19,"['Suryaman, G. K.', 'Soejoedono, R. D.', 'Setiyono, A.', 'Poetri, O. N.', 'Handharyani, E.']",Vet World,,,True
f61c2dbfa5417548e87ffd4da8286b37f9479b09,PMC,Multidose intramuscular allogeneic adipose stem cells decrease the severity of canine atopic dermatitis: A pilot study,http://dx.doi.org/10.14202/vetworld.2019.1747-1754,PMC6925044,32025111,CC BY,"AIM: The aim of this pilot study was to evaluate the therapeutic and safety performance of an intramuscular treatment protocol of multidose of allogeneic adipose stem cells (ASCs) isolated, characterized, and expanded ex vivo from a healthy canine donor. MATERIALS AND METHODS: Twelve dogs diagnosed with canine atopic dermatitis (CAD) were intramuscularly treated with 0.5×10(6) of cryopreserved ASCs from a healthy immunized young canine Ehrlichia canis free donor weekly for 6 weeks. Treatment efficacy was evaluated by the pruritus index and the CAD Lesion Index (CADLI) test. Safety and adverse effects were determined by injection site reaction, weight, blood chemistry, liver function, and whole blood count. RESULTS: Canine ASCs obtained from a donor met the minimum qualities required for this type of cells and showed viability of 90% after thawing. The efficacy of the CADLI score and the pruritus index in 12 dogs with atopic dermatitis was statistically significant efficacy. No adverse reactions were observed at the intramuscular application site, or in relation to animal weight, blood cell populations, or liver and renal function. CONCLUSION: These results suggest that intramuscular administration of cryopreserved ASCs to dogs with atopic dermatitis is a promising cellular therapeutic product for the relief of the symptoms of this disease; however, the duration of the effects obtained with this dose and with other doses should be evaluated, as well as possible immune reactions. As far as we know, this is the first report of the use of multiple intramuscular doses cryopreserved ASCs to treat atopic dermatitis.",2019 Nov 8,"['Enciso, Nathaly', 'Amiel, José', 'Pando, John', 'Enciso, Javier']",Vet World,,,True
17b715fd64ea139c0ed35b555de365b47585da64,PMC,Developing vaccines against epidemic-prone emerging infectious diseases,http://dx.doi.org/10.1007/s00103-019-03061-2,PMC6925075,31776599,CC BY,"Today’s world is characterized by increasing population density, human mobility, urbanization, and climate and ecological change. This global dynamic has various effects, including the increased appearance of emerging infectious diseases (EIDs), which pose a growing threat to global health security. Outbreaks of EIDs, like the 2013–2016 Ebola outbreak in West Africa or the current Ebola outbreak in Democratic Republic of the Congo (DRC), have not only put populations in low- and middle-income countries (LMIC) at risk in terms of morbidity and mortality, but they also have had a significant impact on economic growth in affected regions and beyond. The Coalition for Epidemic Preparedness Innovation (CEPI) is an innovative global partnership between public, private, philanthropic, and civil society organizations that was launched as the result of a consensus that a coordinated, international, and intergovernmental plan was needed to develop and deploy new vaccines to prevent future epidemics. CEPI is focusing on supporting candidate vaccines against the World Health Organization (WHO) Blueprint priority pathogens MERS-CoV, Nipah virus, Lassa fever virus, and Rift Valley fever virus, as well as Chikungunya virus, which is on the WHO watch list. The current vaccine portfolio contains a wide variety of technologies, ranging across recombinant viral vectors, nucleic acids, and recombinant proteins. To support and accelerate vaccine development, CEPI will also support science projects related to the development of biological standards and assays, animal models, epidemiological studies, and diagnostics, as well as build capacities for future clinical trials in risk-prone contexts.",2020 Nov 27,"['Bernasconi, Valentina', 'Kristiansen, Paul A.', 'Whelan, Mike', 'Román, Raúl Gómez', 'Bettis, Alison', 'Yimer, Solomon Abebe', 'Gurry, Céline', 'Andersen, Svein R.', 'Yeskey, Debra', 'Mandi, Henshaw', 'Kumar, Arun', 'Holst, Johan', 'Clark, Carolyn', 'Cramer, Jakob P.', 'Røttingen, John-Arne', 'Hatchett, Richard', 'Saville, Melanie', 'Norheim, Gunnstein']",Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz,,,True
8d3f0c18b7b274179244f57cd8f66e185a009dd5,PMC,Antiviral activity of interleukin-11 as a response to porcine epidemic diarrhea virus infection,http://dx.doi.org/10.1186/s13567-019-0729-9,PMC6925494,31864417,CC BY,"Interleukin-11 (IL-11), a well-known anti-inflammatory factor, provides protection from intestinal epithelium damage caused by physical or chemical factors. However, little is known of the role of IL-11 during viral infections. In this study, IL-11 expression at mRNA and protein levels were found to be high in Vero cells and the jejunum of piglets during porcine epidemic diarrhea virus (PEDV) infection, while IL-11 expression was found to be positively correlated with the level of viral infection. Pretreatment with recombinant porcine IL-11 (pIL-11) was found to suppress PEDV replication in Vero E6 cells, while IL-11 knockdown promoted viral infection. Furthermore, pIL-11 was found to inhibit viral infection by preventing PEDV-mediated apoptosis of cells by activating the IL-11/STAT3 signaling pathway. Conversely, application of a STAT3 phosphorylation inhibitor significantly antagonized the anti-apoptosis function of pIL-11 and counteracted its inhibition of PEDV. Our data suggest that IL-11 is a newfound PEDV-inducible cytokine, and its production enhances the anti-apoptosis ability of epithelial cells against PEDV infection. The potential of IL-11 to be used as a novel therapeutic against devastating viral diarrhea in piglets deserves more attention and study.",2019 Dec 21,"['Li, Yuchen', 'Wu, Qingxin', 'Jin, Yuxin', 'Yang, Qian']",Vet Res,,,True
2aa3a94a43e4f128eed2d9b1190a85cdb39641b7,PMC,Type I Interferon Signaling Disrupts the Hepatic Urea Cycle and Alters Systemic Metabolism to Suppress T Cell Function,http://dx.doi.org/10.1016/j.immuni.2019.10.014,PMC6926485,31784108,CC BY,"Infections induce complex host responses linked to antiviral defense, inflammation, and tissue damage and repair. We hypothesized that the liver, as a central metabolic hub, may orchestrate systemic metabolic changes during infection. We infected mice with chronic lymphocytic choriomeningitis virus (LCMV), performed RNA sequencing and proteomics of liver tissue, and integrated these data with serum metabolomics at different infection phases. Widespread reprogramming of liver metabolism occurred early after infection, correlating with type I interferon (IFN-I) responses. Viral infection induced metabolic alterations of the liver that depended on the interferon alpha/beta receptor (IFNAR1). Hepatocyte-intrinsic IFNAR1 repressed the transcription of metabolic genes, including Otc and Ass1, which encode urea cycle enzymes. This led to decreased arginine and increased ornithine concentrations in the circulation, resulting in suppressed virus-specific CD8(+) T cell responses and ameliorated liver pathology. These findings establish IFN-I-induced modulation of hepatic metabolism and the urea cycle as an endogenous mechanism of immunoregulation. VIDEO ABSTRACT:",2019 Dec 17,"['Lercher, Alexander', 'Bhattacharya, Anannya', 'Popa, Alexandra M.', 'Caldera, Michael', 'Schlapansky, Moritz F.', 'Baazim, Hatoon', 'Agerer, Benedikt', 'Gürtl, Bettina', 'Kosack, Lindsay', 'Májek, Peter', 'Brunner, Julia S.', 'Vitko, Dijana', 'Pinter, Theresa', 'Genger, Jakob-Wendelin', 'Orlova, Anna', 'Pikor, Natalia', 'Reil, Daniela', 'Ozsvár-Kozma, Maria', 'Kalinke, Ulrich', 'Ludewig, Burkhard', 'Moriggl, Richard', 'Bennett, Keiryn L.', 'Menche, Jörg', 'Cheng, Paul N.', 'Schabbauer, Gernot', 'Trauner, Michael', 'Klavins, Kristaps', 'Bergthaler, Andreas']",Immunity,,,False
92288ea020ea1d8c8c0739efe5fa75713d5a9b2a,PMC,Type I Interferon Signaling Disrupts the Hepatic Urea Cycle and Alters Systemic Metabolism to Suppress T Cell Function,http://dx.doi.org/10.1016/j.immuni.2019.10.014,PMC6926485,31784108,CC BY,"Infections induce complex host responses linked to antiviral defense, inflammation, and tissue damage and repair. We hypothesized that the liver, as a central metabolic hub, may orchestrate systemic metabolic changes during infection. We infected mice with chronic lymphocytic choriomeningitis virus (LCMV), performed RNA sequencing and proteomics of liver tissue, and integrated these data with serum metabolomics at different infection phases. Widespread reprogramming of liver metabolism occurred early after infection, correlating with type I interferon (IFN-I) responses. Viral infection induced metabolic alterations of the liver that depended on the interferon alpha/beta receptor (IFNAR1). Hepatocyte-intrinsic IFNAR1 repressed the transcription of metabolic genes, including Otc and Ass1, which encode urea cycle enzymes. This led to decreased arginine and increased ornithine concentrations in the circulation, resulting in suppressed virus-specific CD8(+) T cell responses and ameliorated liver pathology. These findings establish IFN-I-induced modulation of hepatic metabolism and the urea cycle as an endogenous mechanism of immunoregulation. VIDEO ABSTRACT:",2019 Dec 17,"['Lercher, Alexander', 'Bhattacharya, Anannya', 'Popa, Alexandra M.', 'Caldera, Michael', 'Schlapansky, Moritz F.', 'Baazim, Hatoon', 'Agerer, Benedikt', 'Gürtl, Bettina', 'Kosack, Lindsay', 'Májek, Peter', 'Brunner, Julia S.', 'Vitko, Dijana', 'Pinter, Theresa', 'Genger, Jakob-Wendelin', 'Orlova, Anna', 'Pikor, Natalia', 'Reil, Daniela', 'Ozsvár-Kozma, Maria', 'Kalinke, Ulrich', 'Ludewig, Burkhard', 'Moriggl, Richard', 'Bennett, Keiryn L.', 'Menche, Jörg', 'Cheng, Paul N.', 'Schabbauer, Gernot', 'Trauner, Michael', 'Klavins, Kristaps', 'Bergthaler, Andreas']",Immunity,,,False
be570625e254bba4037fddee9d2dd46f892f012e,PMC,Enzootic patterns of Middle East respiratory syndrome coronavirus in imported African and local Arabian dromedary camels: a prospective genomic study,http://dx.doi.org/10.1016/S2542-5196(19)30243-8,PMC6926486,31843456,CC BY,"BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen endemic to the Arabian Peninsula. Dromedary camels are a likely source of infection and the virus probably originated in Africa. We studied the genetic diversity, geographical structure, infection prevalence, and age-associated prevalence among camels at the largest entry port of camels from Africa into the Arabian Peninsula. METHODS: In this prospective genomic study, we took nasal samples from camels imported from Sudan and Djibouti into the Port of Jeddah in Jeddah, Saudi Arabia, over an almost 2-year period and local Arabian camels over 2 months in the year after surveillance of the port. We determined the prevalence of MERS-CoV infection, age-associated patterns of infection, and undertook phylogeographical and migration analyses to determine intercountry virus transmission after local lineage establishment. We compared all virological characteristics between the local and imported cohorts. We compared major gene deletions between African and Arabian strains of the virus. Reproductive numbers were inferred with Bayesian birth death skyline analyses. FINDINGS: Between Aug 10, 2016, and May 3, 2018, we collected samples from 1196 imported camels, of which 868 originated from Sudan and 328 from Djibouti, and between May 1, and June 25, 2018, we collected samples from 472 local camels, of which 189 were from Riyadh and 283 were from Jeddah, Saudi Arabia. Virus prevalence was higher in local camels than in imported camels (224 [47·5%] of 472 vs 157 [13·1%] of 1196; p<0·0001). Infection prevalence peaked among camels older than 1 year and aged up to 2 years in both groups, with 255 (66·9%) of 381 positive cases in this age group. Although the overall geographical distribution of the virus corresponded with the phylogenetic tree topology, some virus exchange was observed between countries corresponding with trade routes in the region. East and west African strains of the virus appear to be geographically separated, with an origin of west African strains in east Africa. African strains of the virus were not re-sampled in Saudi Arabia despite sampling approximately 1 year after importation from Africa. All local Arabian samples contained strains of the virus that belong to a novel recombinant clade (NRC) first detected in 2014 in Saudi Arabia. Reproduction number estimates informed by the sequences suggest sustained endemicity of NRC, with a mean R(e) of 1·16. INTERPRETATION: Despite frequent imports of MERS-CoV with camels from Africa, African lineages of MERS-CoV do not establish themselves in Saudi Arabia. Arabian strains of the virus should be tested for changes in virulence and transmissibility. FUNDING: German Ministry of Research and Education, EU Horizon 2020, and Emerging Diseases Clinical Trials Partnership.",2019 Dec,"['El-Kafrawy, Sherif A', 'Corman, Victor M', 'Tolah, Ahmed M', 'Al Masaudi, Saad B', 'Hassan, Ahmed M', 'Müller, Marcel A', 'Bleicker, Tobias', 'Harakeh, Steve M', 'Alzahrani, Abdulrahman A', 'Alsaaidi, Ghaleb A', 'Alagili, Abdulaziz N', 'Hashem, Anwar M', 'Zumla, Alimuddin', 'Drosten, Christian', 'Azhar, Esam I']",Lancet Planet Health,,,False
f55d236f93a8d11a6265a8c3fdfaa2c32b3af19b,PMC,Association between Hospital Nurses’ Perception of Patient Safety Management and Standard Precaution Adherence: A Cross-Sectional Study,http://dx.doi.org/10.3390/ijerph16234744,PMC6926684,31783559,CC BY,"Standard precautions should be applied to prevent health care-associated infections during every nursing activity. However, adherence to standard precautions was reported to be inadequate. Therefore, this study aimed to identify the rates of standard precaution adherence and the association between perception of patient safety management and standard precaution adherence. In this cross-sectional descriptive study, a convenience sample of nurses was recruited from a university-affiliated teaching hospital in Seoul, Korea. Data were collected using a structured self-report questionnaire. Among the 332 questionnaires returned (response rate: 94.9%), a total of 329 nurses were analyzed. In the present study, the overall standard precaution adherence rate was approximately 53.5%. The multiple linear regression results revealed that participants’ perceptions of patient safety management were only significantly associated with standard precaution adherence after adjusting other covariates (β = 0.412, p < 0.001). Nurse supervisors should focus more on raising awareness about nurses’ perception of patient safety management based on the specific work environment, such as the total number of nurses working together and the nurse-to-patient ratio. Nurse educators should develop integrated curricula to help graduate nurses transition smoothly into professional practice and enhance adherence to standard precautions in diverse health care settings.",2019 Dec 27,"['Lim, Ji-Hye', 'Ahn, Jung-Won', 'Son, Youn-Jung']",Int J Environ Res Public Health,,,True
645773f749cb45b65895645ab7b3c0797566b8b1,PMC,Exit and Entry Screening Practices for Infectious Diseases among Travelers at Points of Entry: Looking for Evidence on Public Health Impact,http://dx.doi.org/10.3390/ijerph16234638,PMC6926871,31766548,CC BY,"A scoping search and a systematic literature review were conducted to give an insight on entry and exit screening referring to travelers at points of entry, by analyzing published evidence on practices, guidelines, and experiences in the past 15 years worldwide. Grey literature, PubMed. and Scopus were searched using specific terms. Most of the available data identified through the systematic literature review concerned entry screening measures at airports. Little evidence is available about entry and exit screening measure implementation and effectiveness at ports and ground crossings. Exit screening was part of the World Health Organisation’s (WHO) temporary recommendations for implementation in certain points of entry, for specific time periods. Exit screening measures for Ebola Virus Disease (EVD) in the three most affected West African countries did not identify any cases and showed zero sensitivity and very low specificity. The percentages of confirmed cases identified out of the total numbers of travelers that passed through entry screening measures in various countries worldwide for Influenza Pandemic (H1N1) and EVD in West Africa were zero or extremely low. Entry screening measures for Severe Acute Respiratory Syndrome (SARS) did not detect any confirmed SARS cases in Australia, Canada, and Singapore. Despite the ineffectiveness of entry and exit screening measures, authors reported several important concomitant positive effects that their impact is difficult to assess, including discouraging travel of ill persons, raising awareness, and educating the traveling public and maintaining operation of flights from/to the affected areas. Exit screening measures in affected areas are important and should be applied jointly with other measures including information strategies, epidemiological investigation, contact tracing, vaccination, and quarantine to achieve a comprehensive outbreak management response. Based on review results, an algorithm about decision-making for entry/exit screening was developed.",2019 Dec 21,"['Mouchtouri, Varvara A.', 'Christoforidou, Eleni P.', 'an der Heiden, Maria', 'Menel Lemos, Cinthia', 'Fanos, Margherita', 'Rexroth, Ute', 'Grote, Ulrike', 'Belfroid, Evelien', 'Swaan, Corien', 'Hadjichristodoulou, Christos']",Int J Environ Res Public Health,,,False
a780aef42860533f02e613494ddb8283b9fbe83d,PMC,Spread of Infectious Disease Modeling and Analysis of Different Factors on Spread of Infectious Disease Based on Cellular Automata,http://dx.doi.org/10.3390/ijerph16234683,PMC6926909,31775236,CC BY,"Infectious diseases are an important cause of human death. The study of the pathogenesis, spread regularity, and development trend of infectious diseases not only provides a theoretical basis for future research on infectious diseases, but also has practical guiding significance for the prevention and control of their spread. In this paper, a controlled differential equation and an objective function of infectious diseases were established by mathematical modeling. Based on cellular automata theory and a compartmental model, the SLIRDS (Susceptible-Latent-Infected-Recovered-Dead-Susceptible) model was constructed, a model which can better reflect the actual infectious process of infectious diseases. Considering the spread of disease in different populations, the model combines population density, sex ratio, and age structure to set the evolution rules of the model. Finally, on the basis of the SLIRDS model, the complex spread process of pandemic influenza A (H1N1) was simulated. The simulation results are similar to the macroscopic characteristics of pandemic influenza A (H1N1) in real life, thus the accuracy and rationality of the SLIRDS model are confirmed.",2019 Dec 25,"['Bin, Sheng', 'Sun, Gengxin', 'Chen, Chih-Cheng']",Int J Environ Res Public Health,,,True
c9895a5f0147dc50b66530f0ffa3a7264559c0a1,PMC,Determining the molecular drivers of species-specific interferon-stimulated gene product 15 interactions with nairovirus ovarian tumor domain proteases,http://dx.doi.org/10.1371/journal.pone.0226415,PMC6927636,31869347,CC0,"Tick-borne nairoviruses (order Bunyavirales) encode an ovarian tumor domain protease (OTU) that suppresses the innate immune response by reversing the post-translational modification of proteins by ubiquitin (Ub) and interferon-stimulated gene product 15 (ISG15). Ub is highly conserved across eukaryotes, whereas ISG15 is only present in vertebrates and shows substantial sequence diversity. Prior attempts to address the effect of ISG15 diversity on viral protein-ISG15 interactions have focused on only a single species’ ISG15 or a limited selection of nairovirus OTUs. To gain a more complete perspective of OTU-ISG15 interactions, we biochemically assessed the relative activities of 14 diverse nairovirus OTUs for 12 species’ ISG15 and found that ISG15 activity is predominantly restricted to particular nairovirus lineages reflecting, in general, known virus-host associations. To uncover the underlying molecular factors driving OTUs affinity for ISG15, X-ray crystal structures of Kupe virus and Ganjam virus OTUs bound to sheep ISG15 were solved and compared to complexes of Crimean-Congo hemorrhagic fever virus and Erve virus OTUs bound to human and mouse ISG15, respectively. Through mutational and structural analysis seven residues in ISG15 were identified that predominantly influence ISG15 species specificity among nairovirus OTUs. Additionally, OTU residues were identified that influence ISG15 preference, suggesting the potential for viral OTUs to adapt to different host ISG15s. These findings provide a foundation to further develop research methods to trace nairovirus-host relationships and delineate the full impact of ISG15 diversity on nairovirus infection.",2019 Dec 23,"['Dzimianski, John V.', 'Scholte, Florine E. M.', 'Williams, Isabelle L.', 'Langley, Caroline', 'Freitas, Brendan T.', 'Spengler, Jessica R.', 'Bergeron, Éric', 'Pegan, Scott D.']",PLoS One,,,True
2cc778640ed3b6327b43f45f83e597a7d912aefd,PMC,Determining the molecular drivers of species-specific interferon-stimulated gene product 15 interactions with nairovirus ovarian tumor domain proteases,http://dx.doi.org/10.1371/journal.pone.0226415,PMC6927636,31869347,CC0,"Tick-borne nairoviruses (order Bunyavirales) encode an ovarian tumor domain protease (OTU) that suppresses the innate immune response by reversing the post-translational modification of proteins by ubiquitin (Ub) and interferon-stimulated gene product 15 (ISG15). Ub is highly conserved across eukaryotes, whereas ISG15 is only present in vertebrates and shows substantial sequence diversity. Prior attempts to address the effect of ISG15 diversity on viral protein-ISG15 interactions have focused on only a single species’ ISG15 or a limited selection of nairovirus OTUs. To gain a more complete perspective of OTU-ISG15 interactions, we biochemically assessed the relative activities of 14 diverse nairovirus OTUs for 12 species’ ISG15 and found that ISG15 activity is predominantly restricted to particular nairovirus lineages reflecting, in general, known virus-host associations. To uncover the underlying molecular factors driving OTUs affinity for ISG15, X-ray crystal structures of Kupe virus and Ganjam virus OTUs bound to sheep ISG15 were solved and compared to complexes of Crimean-Congo hemorrhagic fever virus and Erve virus OTUs bound to human and mouse ISG15, respectively. Through mutational and structural analysis seven residues in ISG15 were identified that predominantly influence ISG15 species specificity among nairovirus OTUs. Additionally, OTU residues were identified that influence ISG15 preference, suggesting the potential for viral OTUs to adapt to different host ISG15s. These findings provide a foundation to further develop research methods to trace nairovirus-host relationships and delineate the full impact of ISG15 diversity on nairovirus infection.",2019 Dec 23,"['Dzimianski, John V.', 'Scholte, Florine E. M.', 'Williams, Isabelle L.', 'Langley, Caroline', 'Freitas, Brendan T.', 'Spengler, Jessica R.', 'Bergeron, Éric', 'Pegan, Scott D.']",PLoS One,,,False
04490b0fff0ad1a55c9ef34663ddeb4a1c430bb9,PMC,Determining the molecular drivers of species-specific interferon-stimulated gene product 15 interactions with nairovirus ovarian tumor domain proteases,http://dx.doi.org/10.1371/journal.pone.0226415,PMC6927636,31869347,CC0,"Tick-borne nairoviruses (order Bunyavirales) encode an ovarian tumor domain protease (OTU) that suppresses the innate immune response by reversing the post-translational modification of proteins by ubiquitin (Ub) and interferon-stimulated gene product 15 (ISG15). Ub is highly conserved across eukaryotes, whereas ISG15 is only present in vertebrates and shows substantial sequence diversity. Prior attempts to address the effect of ISG15 diversity on viral protein-ISG15 interactions have focused on only a single species’ ISG15 or a limited selection of nairovirus OTUs. To gain a more complete perspective of OTU-ISG15 interactions, we biochemically assessed the relative activities of 14 diverse nairovirus OTUs for 12 species’ ISG15 and found that ISG15 activity is predominantly restricted to particular nairovirus lineages reflecting, in general, known virus-host associations. To uncover the underlying molecular factors driving OTUs affinity for ISG15, X-ray crystal structures of Kupe virus and Ganjam virus OTUs bound to sheep ISG15 were solved and compared to complexes of Crimean-Congo hemorrhagic fever virus and Erve virus OTUs bound to human and mouse ISG15, respectively. Through mutational and structural analysis seven residues in ISG15 were identified that predominantly influence ISG15 species specificity among nairovirus OTUs. Additionally, OTU residues were identified that influence ISG15 preference, suggesting the potential for viral OTUs to adapt to different host ISG15s. These findings provide a foundation to further develop research methods to trace nairovirus-host relationships and delineate the full impact of ISG15 diversity on nairovirus infection.",2019 Dec 23,"['Dzimianski, John V.', 'Scholte, Florine E. M.', 'Williams, Isabelle L.', 'Langley, Caroline', 'Freitas, Brendan T.', 'Spengler, Jessica R.', 'Bergeron, Éric', 'Pegan, Scott D.']",PLoS One,,,False
ed92789659fddd64f955bda40d980398b681bb6b,PMC,Are we prepared? The development of performance indicators for public health emergency preparedness using a modified Delphi approach,http://dx.doi.org/10.1371/journal.pone.0226489,PMC6927653,31869359,CC BY,"BACKGROUND: Disasters and emergencies from infectious diseases, extreme weather and anthropogenic events are increasingly common. While risks vary for different communities, disaster and emergency preparedness is recognized as essential for all nation-states. Evidence to inform measurement of preparedness is lacking. The objective of this study was to identify and define a set of public health emergency preparedness (PHEP) indicators to advance performance measurement for local/regional public health agencies. METHODS: A three-round modified Delphi technique was employed to develop indicators for PHEP. The study was conducted in Canada with a national panel of 33 experts and completed in 2018. A list of indicators was derived from the literature. Indicators were rated by importance and actionability until achieving consensus. RESULTS: The scoping review resulted in 62 indicators being included for rating by the panel. Panel feedback provided refinements to indicators and suggestions for new indicators. In total, 76 indicators were proposed for rating across all three rounds; of these, 67 were considered to be important and actionable PHEP indicators. CONCLUSIONS: This study developed an indicator set of 67 PHEP indicators, aligned with a PHEP framework for resilience. The 67 indicators represent important and actionable dimensions of PHEP practice in Canada that can be used by local/regional public health agencies and validated in other jurisdictions to assess readiness and measure improvement in their critical role of protecting community health.",2019 Dec 23,"['Khan, Yasmin', 'Brown, Adalsteinn D.', 'Gagliardi, Anna R.', 'O’Sullivan, Tracey', 'Lacarte, Sara', 'Henry, Bonnie', 'Schwartz, Brian']",PLoS One,,,True
5e3580584a2340a7db087f4115d14f6782e22a36,PMC,The burden and clinical manifestation of hospitalized influenza among different pediatric age‐groups in the tropics,http://dx.doi.org/10.1111/irv.12692,PMC6928028,31608598,CC BY,"INTRODUCTION: In tropical Singapore, influenza occurs all year‐round. This study of influenza‐confirmed hospitalized pediatric patients compared clinical characteristics and complications by age‐group and differences between influenza A and B. METHODS: This was a retrospective study of pediatric inpatients from January 2013 to December 2014. Patients were grouped into: <6 months, 6 months to <5 years, 5‐ to <10‐year and ≥10 years. Complications were classified into neurologic, pulmonary, and other. We also calculated the incidence of hospitalized influenza cases per 100 000 age‐related population. RESULTS: There were a total of 1272 patients with a median age of 37 months. The highest hospitalization rates were in the <6 months age‐group. Majority (75.2%) had no comorbidity; 25.6% had complications: neurologic 11.9%, pulmonary 9.6%, other 4.1%. Patients with other complications were older, male, and had the highest influenza B rates and the longest length of stay. Influenza A comprised 76.9% of cases and had higher complication rates especially neurologic, compared to influenza B. Influenza B patients were older and were more likely to develop other complications. The 6‐month to <5‐year‐age‐group had the highest complication rate (30.6%), especially neurologic. However, ≥10 years old had the highest other complications, ICU/ high‐dependency admissions and influenza B Victoria rates. CONCLUSIONS: Infants <6 months had the highest hospitalization rates for influenza. The 6‐month to <5‐year‐age‐group had the highest complication rate especially neurologic. Influenza A patients were younger, had higher seizure rates and complications compared to influenza B.",2020 Jan 13,"['Chong, Chia‐Yin', 'Yung, Chee‐Fu', 'Gan, Cherie', 'Thio, Szu‐Tien', 'Tan, Natalie Woon‐Hui', 'Tee, Nancy Wen‐Sim', 'Lin, Cui', 'Lin, Raymond Tze‐Pin', 'Thoon, Koh‐Cheng']",Influenza Other Respir Viruses,,,True
e657fc1a1df1ac7f0e7f45a43d405cfda6cda48d,PMC,Lipidomic Profiling Reveals Significant Perturbations of Intracellular Lipid Homeostasis in Enterovirus-Infected Cells,http://dx.doi.org/10.3390/ijms20235952,PMC6928875,31779252,CC BY,"Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) are the most common causes of hand, foot, and mouth disease. Severe EV-A71 and CV-A16 infections may be associated with life-threatening complications. However, the pathogenic mechanisms underlying these severe clinical and pathological features remain incompletely understood. Lipids are known to play critical roles in multiple stages of the virus replication cycle. The specific lipid profile induced upon virus infection is required for optimal virus replication. The perturbations in the host cell lipidomic profiles upon enterovirus infection have not been fully characterized. To this end, we performed ultra-high performance liquid chromatography–electrospray ionization–quadrupole–time of flight-mass spectrometry (UPLC-ESI-Q-TOF-MS)-based lipidomics to characterize the change in host lipidome upon EV-A71 and CV-A16 infections. Our results revealed that 47 lipids within 11 lipid classes were significantly perturbed after EV-A71 and CV-A16 infection. Four polyunsaturated fatty acids (PUFAs), namely, arachidonic acid (AA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and eicosapentaenoic acid (EPA), were consistently upregulated upon EV-A71 and CV-A16 infection. Importantly, exogenously supplying three of these four PUFAs, including AA, DHA, and EPA, in cell cultures significantly reduced EV-A71 and CV-A16 replication. Taken together, our results suggested that enteroviruses might specifically modulate the host lipid pathways for optimal virus replication. Excessive exogenous addition of lipids that disrupted this delicate homeostatic state could prevent efficient viral replication. Precise manipulation of the host lipid profile might be a potential host-targeting antiviral strategy for enterovirus infection.",2019 Nov 26,"['Yan, Bingpeng', 'Zou, Zijiao', 'Chu, Hin', 'Chan, Gabriella', 'Tsang, Jessica Oi-Ling', 'Lai, Pok-Man', 'Yuan, Shuofeng', 'Yip, Cyril Chik-Yan', 'Yin, Feifei', 'Kao, Richard Yi-Tsun', 'Sze, Kong-Hung', 'Lau, Susanna Kar-Pui', 'Chan, Jasper Fuk-Woo', 'Yuen, Kwok-Yung']",Int J Mol Sci,,,True
981110b1eeca795e5d0616f77e56b363178e8887,PMC,Lipidomic Profiling Reveals Significant Perturbations of Intracellular Lipid Homeostasis in Enterovirus-Infected Cells,http://dx.doi.org/10.3390/ijms20235952,PMC6928875,31779252,CC BY,"Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) are the most common causes of hand, foot, and mouth disease. Severe EV-A71 and CV-A16 infections may be associated with life-threatening complications. However, the pathogenic mechanisms underlying these severe clinical and pathological features remain incompletely understood. Lipids are known to play critical roles in multiple stages of the virus replication cycle. The specific lipid profile induced upon virus infection is required for optimal virus replication. The perturbations in the host cell lipidomic profiles upon enterovirus infection have not been fully characterized. To this end, we performed ultra-high performance liquid chromatography–electrospray ionization–quadrupole–time of flight-mass spectrometry (UPLC-ESI-Q-TOF-MS)-based lipidomics to characterize the change in host lipidome upon EV-A71 and CV-A16 infections. Our results revealed that 47 lipids within 11 lipid classes were significantly perturbed after EV-A71 and CV-A16 infection. Four polyunsaturated fatty acids (PUFAs), namely, arachidonic acid (AA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and eicosapentaenoic acid (EPA), were consistently upregulated upon EV-A71 and CV-A16 infection. Importantly, exogenously supplying three of these four PUFAs, including AA, DHA, and EPA, in cell cultures significantly reduced EV-A71 and CV-A16 replication. Taken together, our results suggested that enteroviruses might specifically modulate the host lipid pathways for optimal virus replication. Excessive exogenous addition of lipids that disrupted this delicate homeostatic state could prevent efficient viral replication. Precise manipulation of the host lipid profile might be a potential host-targeting antiviral strategy for enterovirus infection.",2019 Nov 26,"['Yan, Bingpeng', 'Zou, Zijiao', 'Chu, Hin', 'Chan, Gabriella', 'Tsang, Jessica Oi-Ling', 'Lai, Pok-Man', 'Yuan, Shuofeng', 'Yip, Cyril Chik-Yan', 'Yin, Feifei', 'Kao, Richard Yi-Tsun', 'Sze, Kong-Hung', 'Lau, Susanna Kar-Pui', 'Chan, Jasper Fuk-Woo', 'Yuen, Kwok-Yung']",Int J Mol Sci,,,False
4dd9d9ada59d79f3212e4451dd620f25cc84d86d,PMC,Inhibition effects of patchouli alcohol against influenza a virus through targeting cellular PI3K/Akt and ERK/MAPK signaling pathways,http://dx.doi.org/10.1186/s12985-019-1266-x,PMC6929483,31870450,CC BY,"BACKGROUND: Patchouli alcohol (PA) is a tricyclic sesquiterpene extracted from Pogostemonis Herba, which is a traditional Chinese medicine used for therapy of inflammatory diseases. Recent studies have shown that PA has various pharmacological activities, including anti-bacterial and anti-viral effects. METHODS: In this study, the anti-influenza virus (IAV) activities and mechanisms were investigated both in vitro and in vivo. The inhibitory effects of PA against IAV in vitro were evaluated by plaque assay and immunofluorescence assay. The neuraminidase inhibition assay, hemagglutination inhibition (HI) assay, and western blot assay were used to explore the anti-viral mechanisms. The anti-IAV activities in vivo were determined by mice pneumonia model and HE staining. RESULTS: The results showed that PA significantly inhibited different IAV strains multiplication in vitro, and may block IAV infection through inactivating virus particles directly and interfering with some early stages after virus adsorption. Cellular PI3K/Akt and ERK/MAPK signaling pathways may be involved in the anti-IAV actions of PA. Intranasal administration of PA markedly improved mice survival and attenuated pneumonia symptoms in IAV infected mice, comparable to the effects of Oseltamivir. CONCLUSIONS: Therefore, Patchouli alcohol has the potential to be developed into a novel anti-IAV agent in the future.",2019 Dec 23,"['Yu, Yunjia', 'Zhang, Yang', 'Wang, Shuyao', 'Liu, Wei', 'Hao, Cui', 'Wang, Wei']",Virol J,,,True
75356982697a153bdd8610fe024820f7308bb6a2,PMC,Impaired production of immune mediators in dengue virus type 2-infected mononuclear cells of adults with end stage renal disease,http://dx.doi.org/10.1038/s41598-019-56381-3,PMC6930266,31875015,CC BY,"Chronic kidney disease is an epidemiologically identified risk factor for development of severe dengue in dengue-affected patients. However, available data on the immune pathogenesis in end stage renal disease (ESRD) patients affected by dengue is insufficient. We performed an in vitro study to evaluate the sequential immunological reactions and viral load in dengue virus type 2-infected mononuclear cells of patients with ESRD (n = 34) and in healthy controls (n = 30). The concentrations of interleukins (IL)-1 receptor antagonist (Ra), IL-2, IL-6, IL-8, IL-10, IL-12p40, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1b (MIP-1b), vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α and viral load cycle threshold (Ct) were measured in the dengue virus type 2-infected mononuclear cells at 6 h, 24 h, 48 h, and 72 h post-infection. We found in the ESRD group significantly higher GM-CSF and IL-2 levels at 6 h post-infection. However, IL-8, IL-10, IL-12p40, TNF-α, MCP-1, and MIP-1b levels were found significantly lower than in the control group. At 24 h, 48 h, and 72 h post-infection, significantly lower levels of IL-1Ra, IL-6, IL-8, IL-10, IL-12p40, TNF-α, MCP-1, and MIP-1b were detected in ESRD group. Concentration of VEGF at 24 h and 48 h, and of GM-CSF at 48 h and 72 h were also found to be lower in ESRD group than in control group. Compared with controls, the viral load Ct values were significantly lower in ESRD group at 6 h and 24 h post-infection No significant difference in viral load Ct values between two groups was found at 48 h and 72 h post-infection. Our study discloses that the expression of immune mediators of dengue-infected mononuclear cells is impaired in ESRD patients.",2019 Dec 24,"['Lee, Ing-Kit', 'Yang, Zih-Syuan', 'Ng, Hwee-Yeong', 'Li, Lung-Chih', 'Huang, Wen-Chi', 'Chen, Yi-Chun', 'Tsai, Ching-Yen', 'Lee, Chien-Te']",Sci Rep,,,True
30292ad7f0b45c12878cab23e909fcdeb38bdf7e,PMC,Inhibition of Porcine Aminopeptidase M (pAMP) by the Pentapeptide Microginins,http://dx.doi.org/10.3390/molecules24234369,PMC6930480,31795383,CC BY,"Aminopeptidase M (AMP) inhibition is of interest for several diseases, such as highly vascularized cancer types. AMP can be inhibited by linear pentapeptides isolated from Microcystis aeruginosa LTPNA08 (MG7XX). Porcine AMP inhibition—a model for human AMP—activity was spectrophotometrically measured by the formation of p-nitroanilide from L-leucine-p-nitroanilide substrate by AMP. AMP inhibition by MG770 exhibited comparable inhibition levels to amastatin (IC(50) values: 1.20 ± 0.1 μM and 0.98 ± 0.1 μM, respectively), while MG756 was slightly less potent (with IC(50) values of 3.26 ± 0.5 μM). Molecular modelling suggests a potential binding mode, based on the interaction with the Zn(2+) cofactor, where MG770′s extra methyl group contributes to the disturbance of the Zn(2+) cofactor complex and highlights the importance of hydrophobicity for the site.",2019 Nov 29,"['Ferreira, Glaucio Monteiro', 'Kronenberger, Thales', 'de Almeida, Éryka Costa', 'Sampaio, Joseane', 'Terra, Clélia Ferreira', 'Pinto, Ernani', 'Trossini, Gustavo Henrique Goulart']",Molecules,,,True
6802b8466abb3a7c33a5736046c1f5dc373d5ce8,PMC,Inhibition of Porcine Aminopeptidase M (pAMP) by the Pentapeptide Microginins,http://dx.doi.org/10.3390/molecules24234369,PMC6930480,31795383,CC BY,"Aminopeptidase M (AMP) inhibition is of interest for several diseases, such as highly vascularized cancer types. AMP can be inhibited by linear pentapeptides isolated from Microcystis aeruginosa LTPNA08 (MG7XX). Porcine AMP inhibition—a model for human AMP—activity was spectrophotometrically measured by the formation of p-nitroanilide from L-leucine-p-nitroanilide substrate by AMP. AMP inhibition by MG770 exhibited comparable inhibition levels to amastatin (IC(50) values: 1.20 ± 0.1 μM and 0.98 ± 0.1 μM, respectively), while MG756 was slightly less potent (with IC(50) values of 3.26 ± 0.5 μM). Molecular modelling suggests a potential binding mode, based on the interaction with the Zn(2+) cofactor, where MG770′s extra methyl group contributes to the disturbance of the Zn(2+) cofactor complex and highlights the importance of hydrophobicity for the site.",2019 Nov 29,"['Ferreira, Glaucio Monteiro', 'Kronenberger, Thales', 'de Almeida, Éryka Costa', 'Sampaio, Joseane', 'Terra, Clélia Ferreira', 'Pinto, Ernani', 'Trossini, Gustavo Henrique Goulart']",Molecules,,,False
0727980b80bddd2728174a65e08275cf73000f7f,PMC,Iron Transport Tocopheryl Polyethylene Glycol Succinate in Animal Health and Diseases,http://dx.doi.org/10.3390/molecules24234289,PMC6930530,31775281,CC BY,"Gut health is the starting place for maintaining the overall health of an animal. Strategies to maintain gut health are, thus, an important part in achieving the goal of improving animal health. A new strategy to do this involves two molecules: the iron transport protein ovotransferrin (IT) and α-tocopheryl polyethylene glycol succinate (TPGS), which result in the novel formulation of ITPGS. These molecules help reduce gut pathogens, while enhancing the absorption and bioavailability of therapeutic drugs, phytomedicines, and nanomedicines. This, in turn, helps to maintain normal health in animals. Maintaining the gastrointestinal tract (GIT) in its normal condition is key for successful absorption and efficacy of any nutrient. A compromised GIT, due to an imbalance (dysbiosis) in the GIT microbiome, can lead to an impaired GI barrier system with impaired absorption and overall health of the animal. The molecules in ITPGS may address the issue of poor absorption by keeping the GI system healthy by maintaining the normal microbiome and improving the absorption of nutrients through multiple mechanisms involving antioxidative, anti-inflammatory, immunomodulatory, and antimicrobial activities. The ITPGS technology can allow the dose of active pharmaceutical or herbal medicine to be significantly reduced in order to attain equal or better efficacy. With complimentary actions between IT and TPGS, ITPGS presents a novel approach to increase the bioavailability of drugs, phytoconstituents, nutrients, and nanomedicines by enhanced transport to the tissues at the site of action, while reducing gut pathogen load. The ITPGS approach appears to be a novel strategy for maintaining the health of animals by manipulation of microbiota.",2019 Nov 25,"['Srivastava, Ajay', 'Lall, Rajiv', 'Talukder, Jamil', 'DuBourdieu, Dan', 'Gupta, Ramesh C.']",Molecules,,,True
1ee81584a0fbdae5f787c41b02ba330bc46b545c,PMC,A Subcellular Quantitative Proteomic Analysis of Herpes Simplex Virus Type 1-Infected HEK 293T Cells,http://dx.doi.org/10.3390/molecules24234215,PMC6930547,31757042,CC BY,"Herpes simplex virus type 1 (HSV-1) is widespread double-stranded DNA (dsDNA) virus that establishes life-long latency and causes diverse severe symptoms. The mechanisms of HSV-1 infection and HSV-1’s interactions with various host cells have been studied and reviewed extensively. Type I interferons were secreted by host cells upon HSV infection and play a vital role in controlling virus proliferation. A few studies, however, have focused on HSV-1 infection without the presence of interferon (IFN) signaling. In this study, HEK 293T cells with low toll-like receptor (TLR) and stimulator of interferon genes protein (STING) expression were infected with HSV-1 and subjected to a quantitative proteomic analysis. By using a subcellular fractionation strategy and high-performance mass spectrometry, a total of 6607 host proteins were quantified, of which 498 proteins were differentially regulated. A bioinformatics analysis indicated that multiple signaling pathways might be involved in HSV-1 infection. A further functional study indicated the role of Interferon-induced transmembrane protein 3 (IFITM3), Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2), and Tripartite motif-containing protein 27 (TRIM27) in inhibiting viral DNA replication and proliferation. Our data provide a global view of host responses to HSV-1 infection in HEK 293T cells and identify the proteins involved in the HSV-1 infection process.",2019 Nov 20,"['Wan, Weiwei', 'Wang, Liangjie', 'Chen, Xi', 'Zhu, Shenglin', 'Shang, Weijuan', 'Xiao, Gengfu', 'Zhang, Lei-Ke']",Molecules,,,True
fd0757a0cb205513bc3861bcfb52a38eb582b3bc,PMC,"Airport Entry and Exit Screening during the Ebola Virus Disease Outbreak in Sierra Leone, 2014 to 2016",http://dx.doi.org/10.1155/2019/3832790,PMC6930773,31915689,CC BY,"We present entry and exit screening outcomes on all persons passing through Freetown International Airport (FNA) in Sierra Leone during the period 1(st) September 2014 to 4(th) February 2016. A total of 166,242 persons underwent screening for Ebola Virus Disease (EVD) at FNA. Five persons were denied air travel from Sierra Leone after secondary screening. Laboratory testing revealed none were positive for EVD. No cases were identified through entry screening route. The public health value of airport screening for EVD is discussed.",2019 Oct 20,"Wickramage, Kolitha",Biomed Res Int,,,False
8103f6b3e1b33043c0a2836e1e5c45cf80e665a5,PMC,"Airport Entry and Exit Screening during the Ebola Virus Disease Outbreak in Sierra Leone, 2014 to 2016",http://dx.doi.org/10.1155/2019/3832790,PMC6930773,31915689,CC BY,"We present entry and exit screening outcomes on all persons passing through Freetown International Airport (FNA) in Sierra Leone during the period 1(st) September 2014 to 4(th) February 2016. A total of 166,242 persons underwent screening for Ebola Virus Disease (EVD) at FNA. Five persons were denied air travel from Sierra Leone after secondary screening. Laboratory testing revealed none were positive for EVD. No cases were identified through entry screening route. The public health value of airport screening for EVD is discussed.",2019 Oct 20,"Wickramage, Kolitha",Biomed Res Int,,,True
4c0a84d9d35e76db288afca33c1f63c27d436328,PMC,A Mini-Review of Adverse Lung Transplant Outcomes Associated With Respiratory Viruses,http://dx.doi.org/10.3389/fimmu.2019.02861,PMC6930876,31921130,CC BY,"Due to their overall immunocompromised state, lung transplant recipients (LTRs) are at increased risk for the development of viral respiratory infections compared to the general population. Such respiratory infections often lead to poor transplant outcomes. We performed a systematic review of the last 30 years of medical literature to summarize the impact of specific respiratory viruses on LTRs. After screening 2,150 articles for potential inclusion, 39 manuscripts were chosen for final review. We found evidence for an association of respiratory viruses including respiratory syncytial virus (RSV), parainfluenza virus, and influenza viruses with increased morbidity following transplant. Through the literature search, we also documented associations of RSV and adenovirus infections with increased mortality among LTRs. We posit that the medical literature supports aggressive surveillance for respiratory viruses among this population.",2019 Dec 19,"['Bailey, Emily S.', 'Zemke, Juliana N.', 'Choi, Jessica Y.', 'Gray, Gregory C.']",Front Immunol,,,True
8666c802be0f784cd46d8a002832de0d7a2e62e5,PMC,Reprogramming the unfolded protein response for replication by porcine reproductive and respiratory syndrome virus,http://dx.doi.org/10.1371/journal.ppat.1008169,PMC6932825,31738790,CC BY,"The unfolded protein response (UPR) in the endoplasmic reticulum (ER) constitutes a critical component of host innate immunity against microbial infections. In this report, we show that porcine reproductive and respiratory syndrome virus (PRRSV) utilizes the UPR machinery for its own benefit. We provide evidence that the virus targets the UPR central regulator GRP78 for proteasomal degradation via a mechanism that requires viral glycoprotein GP2a, while both IRE1-XBP1s and PERK-eIF2α-ATF4 signaling branches of the UPR are turned on at early stage of infection. The activated effector XBP1s was found to enter the nucleus, but ATF4 was unexpectedly diverted to cytoplasmic viral replication complexes by means of nonstructural proteins nsp2/3 to promote viral RNA synthesis. RNAi knockdown of either ATF4 or XBP1s dramatically attenuated virus titers, while overexpression caused increases. These observations reveal attractive host targets (e.g., ATF4 and XBP1s) for antiviral drugs and have implications in vaccine development.",2019 Nov 18,"['Gao, Peng', 'Chai, Yue', 'Song, Jiangwei', 'Liu, Teng', 'Chen, Peng', 'Zhou, Lei', 'Ge, Xinna', 'Guo, Xin', 'Han, Jun', 'Yang, Hanchun']",PLoS Pathog,,,True
67d23e2a0388959fbee3dfa60b7097acaebfe4dc,PMC,IILLS: predicting virus-receptor interactions based on similarity and semi-supervised learning,http://dx.doi.org/10.1186/s12859-019-3278-3,PMC6933616,31881820,CC BY,"BACKGROUND: Viral infectious diseases are the serious threat for human health. The receptor-binding is the first step for the viral infection of hosts. To more effectively treat human viral infectious diseases, the hidden virus-receptor interactions must be discovered. However, current computational methods for predicting virus-receptor interactions are limited. RESULT: In this study, we propose a new computational method (IILLS) to predict virus-receptor interactions based on Initial Interaction scores method via the neighbors and the Laplacian regularized Least Square algorithm. IILLS integrates the known virus-receptor interactions and amino acid sequences of receptors. The similarity of viruses is calculated by the Gaussian Interaction Profile (GIP) kernel. On the other hand, we also compute the receptor GIP similarity and the receptor sequence similarity. Then the sequence similarity is used as the final similarity of receptors according to the prediction results. The 10-fold cross validation (10CV) and leave one out cross validation (LOOCV) are used to assess the prediction performance of our method. We also compare our method with other three competing methods (BRWH, LapRLS, CMF). CONLUSION: The experiment results show that IILLS achieves the AUC values of 0.8675 and 0.9061 with the 10-fold cross validation and leave-one-out cross validation (LOOCV), respectively, which illustrates that IILLS is superior to the competing methods. In addition, the case studies also further indicate that the IILLS method is effective for the virus-receptor interaction prediction.",2019 Dec 27,"['Yan, Cheng', 'Duan, Guihua', 'Wu, Fang-Xiang', 'Wang, Jianxin']",BMC Bioinformatics,,,True
f73808579d362b40e0f9c8ef0d87868a0e3e3481,PMC,An efficient simulated annealing algorithm for the RNA secondary structure prediction with Pseudoknots,http://dx.doi.org/10.1186/s12864-019-6300-2,PMC6933665,31881969,CC BY,"BACKGROUND: RNA pseudoknot structures play an important role in biological processes. However, existing RNA secondary structure prediction algorithms cannot predict the pseudoknot structure efficiently. Although random matching can improve the number of base pairs, these non-consecutive base pairs cannot make contributions to reduce the free energy. RESULT: In order to improve the efficiency of searching procedure, our algorithm take consecutive base pairs as the basic components. Firstly, our algorithm calculates and archive all the consecutive base pairs in triplet data structure, if the number of consecutive base pairs is greater than given minimum stem length. Secondly, the annealing schedule is adapted to select the optimal solution that has minimum free energy. Finally, the proposed algorithm is evaluated with the real instances in PseudoBase. CONCLUSION: The experimental results have been demonstrated to provide a competitive and oftentimes better performance when compared against some chosen state-of-the-art RNA structure prediction algorithms.",2019 Dec 27,"['Kai, Zhang', 'Yuting, Wang', 'Yulin, Lv', 'Jun, Liu', 'Juanjuan, He']",BMC Genomics,,,True
479ade65b7f5219559c4d8cc48c1c2f90bda977f,PMC,The ability of single genes vs full genomes to resolve time and space in outbreak analysis,http://dx.doi.org/10.1186/s12862-019-1567-0,PMC6933756,31878875,CC BY,"BACKGROUND: Inexpensive pathogen genome sequencing has had a transformative effect on the field of phylodynamics, where ever increasing volumes of data have promised real-time insight into outbreaks of infectious disease. As well as the sheer volume of pathogen isolates being sequenced, the sequencing of whole pathogen genomes, rather than select loci, has allowed phylogenetic analyses to be carried out at finer time scales, often approaching serial intervals for infections caused by rapidly evolving RNA viruses. Despite its utility, whole genome sequencing of pathogens has not been adopted universally and targeted sequencing of loci is common in some pathogen-specific fields. RESULTS: In this study we highlighted the utility of sequencing whole genomes of pathogens by re-analysing a well-characterised collection of Ebola virus sequences in the form of complete viral genomes (≈19 kb long) or the rapidly evolving glycoprotein (GP, ≈2 kb long) gene. We have quantified changes in phylogenetic, temporal, and spatial inference resolution as a result of this reduction in data and compared these to theoretical expectations. CONCLUSIONS: We propose a simple intuitive metric for quantifying temporal resolution, i.e. the time scale over which sequence data might be informative of various processes as a quick back-of-the-envelope calculation of statistical power available to molecular clock analyses.",2019 Dec 26,"['Dudas, Gytis', 'Bedford, Trevor']",BMC Evol Biol,,,True
baae1b488b6763192f01d394138315d92f75c426,PMC,Comparison of the Panther Fusion and Allplex assays for the detection of respiratory viruses in clinical samples,http://dx.doi.org/10.1371/journal.pone.0226403,PMC6934309,31881030,CC BY,"Respiratory viral infections are the most frequent clinical syndrome affecting both children and adults, and early detection is fundamental to avoid infection-related risks and reduce the healthcare costs incurred by unnecessary antibiotic treatments. In this study, performance characteristics of two commercial methods, the Panther Fusion® assay (Hologic Inc., San Diego, CA, USA) were compared to Allplex(™) respiratory panels (Seegene, Seoul, South Korea) for the detection of influenza A (Flu A), influenza B (Flu B), respiratory syncytial virus (RSV), parainfluenza virus (PIV), human metapneumovirus (hMPV), rhinovirus (RV) and adenovirus (AdV) targets. A total of 865 specimens collected prospectively and retrospectively were included, and discordant results were further examined using another commercial product, R-GENE(™) respiratory kits (bioMérieux, Marcy l’Etoile, France). There was high agreement between both methods, with 98.6% concordance and a kappa (k) value of 0.9 (95% CI: 0.89–0.92). A specific analysis of both methods for each viral agent demonstrated comparable sensitivity and specificity, both ranging from 0.83 to 1 with good predictive values for the prospective part of the study. Good agreement between both methods was also found for the κ values obtained (ranging from 97.55% to 98.9%), with the lowest for hMPV (k = 0.83, 95% CI: 0.75–0.91) and RV (k = 0.73, 95% CI: 0.65–0.81). Amplification efficiency, measured according to the value of the cycle threshold (C(t)) obtained in each of the amplifications in both tests, was significantly better with Panther Fusion for Flu A, Flu B, hMPV and RV. Regarding discordant results, R-GENE showed higher agreement with Panther Fusion-positive specimens (negative for Allplex; n = 28/71, 34.9%) than with Allplex-positive samples (negative for Panther Fusion; n = 7/49, 14.3%). In summary, Panther Fusion proved to be a more efficient fully-automated methodology, requiring shorter hands-on and turnaround times than Allplex.",2019 Dec 27,"['Folgueira, Lola', 'Moral, Noelia', 'Pascual, Consuelo', 'Delgado, Rafael']",PLoS One,,,True
e6e057796aa14fa1808ee7076da0109362acb7c9,PMC,Effect of thermal control of dry fomites on regulating the survival of human pathogenic bacteria responsible for nosocomial infections,http://dx.doi.org/10.1371/journal.pone.0226952,PMC6934310,31881059,CC BY,"We monitored the survival of human pathogenic bacteria [Escherichia coli (ATCC), extended-spectrum β-lactamase-producing E. coli (Clinical isolate), New Delhi metallo-β-lactamase-producing E. coli (clinical isolate), Staphylococcus aureus (ATCC)] on dry materials (vinyl chloride, aluminum, plastic, stainless steel) at distinct temperatures (room temperature or 15°C–37°C). These bacteria favored a lower temperature for their prolonged survival on the dry fomites, regardless of the material type. Interestingly, when mixed with S. aureus, E. coli survived for a longer time at a lower temperature. Cardiolipin, which can promote the survival of S. aureus in harsh environments, had no effect on maintaining the survival of E. coli. Although the trends remained unchanged, adjusting the humidity from 40% to 60% affected the survival of bacteria on dry surfaces. Scanning electron microscopic analysis revealed no morphological differences in these bacteria immediately before or after one day of dry conditions. In addition, ATP assessment, a method used to visualize high-touch surfaces in hospitals, was not effective at monitoring bacterial dynamics. A specialized handrail device fitted with a heater, which was maintained at normal human body core temperature, successfully prohibited the prolonged survival of bacteria [Enterococcus faecalis (ATCC), E. coli (ATCC), Pseudomonas aeruginosa (ATCC), S. aureus (ATCC), Acinetobacter baumannii (clinical isolate), and Serratia marcescens (clinical isolate)], with the exception of spore-forming Bacillus subtilis (from our laboratory collection) and the yeast-like fungus Candida albicans (from our laboratory collection)] on dry surfaces. Taken together, we concluded that the tested bacteria favor lower temperatures for their survival in dry environments. Therefore, the thermal control of dry fomites has the potential to control bacterial survival on high-touch surfaces in hospitals.",2019 Dec 27,"['Shimoda, Tomoko', 'Okubo, Torahiko', 'Enoeda, Yoshiki', 'Yano, Rika', 'Nakamura, Shinji', 'Thapa, Jeewan', 'Yamaguchi, Hiroyuki']",PLoS One,,,True
83c7a66903c306729d7726ce6a778bd4c6f24744,PMC,Effect of thermal control of dry fomites on regulating the survival of human pathogenic bacteria responsible for nosocomial infections,http://dx.doi.org/10.1371/journal.pone.0226952,PMC6934310,31881059,CC BY,"We monitored the survival of human pathogenic bacteria [Escherichia coli (ATCC), extended-spectrum β-lactamase-producing E. coli (Clinical isolate), New Delhi metallo-β-lactamase-producing E. coli (clinical isolate), Staphylococcus aureus (ATCC)] on dry materials (vinyl chloride, aluminum, plastic, stainless steel) at distinct temperatures (room temperature or 15°C–37°C). These bacteria favored a lower temperature for their prolonged survival on the dry fomites, regardless of the material type. Interestingly, when mixed with S. aureus, E. coli survived for a longer time at a lower temperature. Cardiolipin, which can promote the survival of S. aureus in harsh environments, had no effect on maintaining the survival of E. coli. Although the trends remained unchanged, adjusting the humidity from 40% to 60% affected the survival of bacteria on dry surfaces. Scanning electron microscopic analysis revealed no morphological differences in these bacteria immediately before or after one day of dry conditions. In addition, ATP assessment, a method used to visualize high-touch surfaces in hospitals, was not effective at monitoring bacterial dynamics. A specialized handrail device fitted with a heater, which was maintained at normal human body core temperature, successfully prohibited the prolonged survival of bacteria [Enterococcus faecalis (ATCC), E. coli (ATCC), Pseudomonas aeruginosa (ATCC), S. aureus (ATCC), Acinetobacter baumannii (clinical isolate), and Serratia marcescens (clinical isolate)], with the exception of spore-forming Bacillus subtilis (from our laboratory collection) and the yeast-like fungus Candida albicans (from our laboratory collection)] on dry surfaces. Taken together, we concluded that the tested bacteria favor lower temperatures for their survival in dry environments. Therefore, the thermal control of dry fomites has the potential to control bacterial survival on high-touch surfaces in hospitals.",2019 Dec 27,"['Shimoda, Tomoko', 'Okubo, Torahiko', 'Enoeda, Yoshiki', 'Yano, Rika', 'Nakamura, Shinji', 'Thapa, Jeewan', 'Yamaguchi, Hiroyuki']",PLoS One,,,False
58654073410779249fcd789d116f5537c87c5357,PMC,Effect of thermal control of dry fomites on regulating the survival of human pathogenic bacteria responsible for nosocomial infections,http://dx.doi.org/10.1371/journal.pone.0226952,PMC6934310,31881059,CC BY,"We monitored the survival of human pathogenic bacteria [Escherichia coli (ATCC), extended-spectrum β-lactamase-producing E. coli (Clinical isolate), New Delhi metallo-β-lactamase-producing E. coli (clinical isolate), Staphylococcus aureus (ATCC)] on dry materials (vinyl chloride, aluminum, plastic, stainless steel) at distinct temperatures (room temperature or 15°C–37°C). These bacteria favored a lower temperature for their prolonged survival on the dry fomites, regardless of the material type. Interestingly, when mixed with S. aureus, E. coli survived for a longer time at a lower temperature. Cardiolipin, which can promote the survival of S. aureus in harsh environments, had no effect on maintaining the survival of E. coli. Although the trends remained unchanged, adjusting the humidity from 40% to 60% affected the survival of bacteria on dry surfaces. Scanning electron microscopic analysis revealed no morphological differences in these bacteria immediately before or after one day of dry conditions. In addition, ATP assessment, a method used to visualize high-touch surfaces in hospitals, was not effective at monitoring bacterial dynamics. A specialized handrail device fitted with a heater, which was maintained at normal human body core temperature, successfully prohibited the prolonged survival of bacteria [Enterococcus faecalis (ATCC), E. coli (ATCC), Pseudomonas aeruginosa (ATCC), S. aureus (ATCC), Acinetobacter baumannii (clinical isolate), and Serratia marcescens (clinical isolate)], with the exception of spore-forming Bacillus subtilis (from our laboratory collection) and the yeast-like fungus Candida albicans (from our laboratory collection)] on dry surfaces. Taken together, we concluded that the tested bacteria favor lower temperatures for their survival in dry environments. Therefore, the thermal control of dry fomites has the potential to control bacterial survival on high-touch surfaces in hospitals.",2019 Dec 27,"['Shimoda, Tomoko', 'Okubo, Torahiko', 'Enoeda, Yoshiki', 'Yano, Rika', 'Nakamura, Shinji', 'Thapa, Jeewan', 'Yamaguchi, Hiroyuki']",PLoS One,,,False
25c042a48810873c4413412f81c4385e78bd6013,PMC,Effect of thermal control of dry fomites on regulating the survival of human pathogenic bacteria responsible for nosocomial infections,http://dx.doi.org/10.1371/journal.pone.0226952,PMC6934310,31881059,CC BY,"We monitored the survival of human pathogenic bacteria [Escherichia coli (ATCC), extended-spectrum β-lactamase-producing E. coli (Clinical isolate), New Delhi metallo-β-lactamase-producing E. coli (clinical isolate), Staphylococcus aureus (ATCC)] on dry materials (vinyl chloride, aluminum, plastic, stainless steel) at distinct temperatures (room temperature or 15°C–37°C). These bacteria favored a lower temperature for their prolonged survival on the dry fomites, regardless of the material type. Interestingly, when mixed with S. aureus, E. coli survived for a longer time at a lower temperature. Cardiolipin, which can promote the survival of S. aureus in harsh environments, had no effect on maintaining the survival of E. coli. Although the trends remained unchanged, adjusting the humidity from 40% to 60% affected the survival of bacteria on dry surfaces. Scanning electron microscopic analysis revealed no morphological differences in these bacteria immediately before or after one day of dry conditions. In addition, ATP assessment, a method used to visualize high-touch surfaces in hospitals, was not effective at monitoring bacterial dynamics. A specialized handrail device fitted with a heater, which was maintained at normal human body core temperature, successfully prohibited the prolonged survival of bacteria [Enterococcus faecalis (ATCC), E. coli (ATCC), Pseudomonas aeruginosa (ATCC), S. aureus (ATCC), Acinetobacter baumannii (clinical isolate), and Serratia marcescens (clinical isolate)], with the exception of spore-forming Bacillus subtilis (from our laboratory collection) and the yeast-like fungus Candida albicans (from our laboratory collection)] on dry surfaces. Taken together, we concluded that the tested bacteria favor lower temperatures for their survival in dry environments. Therefore, the thermal control of dry fomites has the potential to control bacterial survival on high-touch surfaces in hospitals.",2019 Dec 27,"['Shimoda, Tomoko', 'Okubo, Torahiko', 'Enoeda, Yoshiki', 'Yano, Rika', 'Nakamura, Shinji', 'Thapa, Jeewan', 'Yamaguchi, Hiroyuki']",PLoS One,,,False
7b18553b61e946d26174e79b66009ef7e7c6b7f8,PMC,Effect of thermal control of dry fomites on regulating the survival of human pathogenic bacteria responsible for nosocomial infections,http://dx.doi.org/10.1371/journal.pone.0226952,PMC6934310,31881059,CC BY,"We monitored the survival of human pathogenic bacteria [Escherichia coli (ATCC), extended-spectrum β-lactamase-producing E. coli (Clinical isolate), New Delhi metallo-β-lactamase-producing E. coli (clinical isolate), Staphylococcus aureus (ATCC)] on dry materials (vinyl chloride, aluminum, plastic, stainless steel) at distinct temperatures (room temperature or 15°C–37°C). These bacteria favored a lower temperature for their prolonged survival on the dry fomites, regardless of the material type. Interestingly, when mixed with S. aureus, E. coli survived for a longer time at a lower temperature. Cardiolipin, which can promote the survival of S. aureus in harsh environments, had no effect on maintaining the survival of E. coli. Although the trends remained unchanged, adjusting the humidity from 40% to 60% affected the survival of bacteria on dry surfaces. Scanning electron microscopic analysis revealed no morphological differences in these bacteria immediately before or after one day of dry conditions. In addition, ATP assessment, a method used to visualize high-touch surfaces in hospitals, was not effective at monitoring bacterial dynamics. A specialized handrail device fitted with a heater, which was maintained at normal human body core temperature, successfully prohibited the prolonged survival of bacteria [Enterococcus faecalis (ATCC), E. coli (ATCC), Pseudomonas aeruginosa (ATCC), S. aureus (ATCC), Acinetobacter baumannii (clinical isolate), and Serratia marcescens (clinical isolate)], with the exception of spore-forming Bacillus subtilis (from our laboratory collection) and the yeast-like fungus Candida albicans (from our laboratory collection)] on dry surfaces. Taken together, we concluded that the tested bacteria favor lower temperatures for their survival in dry environments. Therefore, the thermal control of dry fomites has the potential to control bacterial survival on high-touch surfaces in hospitals.",2019 Dec 27,"['Shimoda, Tomoko', 'Okubo, Torahiko', 'Enoeda, Yoshiki', 'Yano, Rika', 'Nakamura, Shinji', 'Thapa, Jeewan', 'Yamaguchi, Hiroyuki']",PLoS One,,,False
3d4d1d2ba6ac78dfc07b03629f2f0076e12418c1,PMC,Effect of thermal control of dry fomites on regulating the survival of human pathogenic bacteria responsible for nosocomial infections,http://dx.doi.org/10.1371/journal.pone.0226952,PMC6934310,31881059,CC BY,"We monitored the survival of human pathogenic bacteria [Escherichia coli (ATCC), extended-spectrum β-lactamase-producing E. coli (Clinical isolate), New Delhi metallo-β-lactamase-producing E. coli (clinical isolate), Staphylococcus aureus (ATCC)] on dry materials (vinyl chloride, aluminum, plastic, stainless steel) at distinct temperatures (room temperature or 15°C–37°C). These bacteria favored a lower temperature for their prolonged survival on the dry fomites, regardless of the material type. Interestingly, when mixed with S. aureus, E. coli survived for a longer time at a lower temperature. Cardiolipin, which can promote the survival of S. aureus in harsh environments, had no effect on maintaining the survival of E. coli. Although the trends remained unchanged, adjusting the humidity from 40% to 60% affected the survival of bacteria on dry surfaces. Scanning electron microscopic analysis revealed no morphological differences in these bacteria immediately before or after one day of dry conditions. In addition, ATP assessment, a method used to visualize high-touch surfaces in hospitals, was not effective at monitoring bacterial dynamics. A specialized handrail device fitted with a heater, which was maintained at normal human body core temperature, successfully prohibited the prolonged survival of bacteria [Enterococcus faecalis (ATCC), E. coli (ATCC), Pseudomonas aeruginosa (ATCC), S. aureus (ATCC), Acinetobacter baumannii (clinical isolate), and Serratia marcescens (clinical isolate)], with the exception of spore-forming Bacillus subtilis (from our laboratory collection) and the yeast-like fungus Candida albicans (from our laboratory collection)] on dry surfaces. Taken together, we concluded that the tested bacteria favor lower temperatures for their survival in dry environments. Therefore, the thermal control of dry fomites has the potential to control bacterial survival on high-touch surfaces in hospitals.",2019 Dec 27,"['Shimoda, Tomoko', 'Okubo, Torahiko', 'Enoeda, Yoshiki', 'Yano, Rika', 'Nakamura, Shinji', 'Thapa, Jeewan', 'Yamaguchi, Hiroyuki']",PLoS One,,,False
832b1861e334121672bb60f1d917481353cf4327,PMC,Estimation of temporal covariances in pathogen dynamics using Bayesian multivariate autoregressive models,http://dx.doi.org/10.1371/journal.pcbi.1007492,PMC6934324,31834896,CC BY,"It is well recognised that animal and plant pathogens form complex ecological communities of interacting organisms within their hosts, and there is growing interest in the health implications of such pathogen interactions. Although community ecology approaches have been used to identify pathogen interactions at the within-host scale, methodologies enabling robust identification of interactions from population-scale data such as that available from health authorities are lacking. To address this gap, we developed a statistical framework that jointly identifies interactions between multiple viruses from contemporaneous non-stationary infection time series. Our conceptual approach is derived from a Bayesian multivariate disease mapping framework. Importantly, our approach captures within- and between-year dependencies in infection risk while controlling for confounding factors such as seasonality, demographics and infection frequencies, allowing genuine pathogen interactions to be distinguished from simple correlations. We validated our framework using a broad range of synthetic data. We then applied it to diagnostic data available for five respiratory viruses co-circulating in a major urban population between 2005 and 2013: adenovirus, human coronavirus, human metapneumovirus, influenza B virus and respiratory syncytial virus. We found positive and negative covariances indicative of epidemiological interactions among specific virus pairs. This statistical framework enables a community ecology perspective to be applied to infectious disease epidemiology with important utility for public health planning and preparedness.",2019 Dec 13,"['Mair, Colette', 'Nickbakhsh, Sema', 'Reeve, Richard', 'McMenamin, Jim', 'Reynolds, Arlene', 'Gunson, Rory N.', 'Murcia, Pablo R.', 'Matthews, Louise']",PLoS Comput Biol,,,True
1dcadaca679e086ee5c486c056d0d78969523c50,PMC,Estimation of temporal covariances in pathogen dynamics using Bayesian multivariate autoregressive models,http://dx.doi.org/10.1371/journal.pcbi.1007492,PMC6934324,31834896,CC BY,"It is well recognised that animal and plant pathogens form complex ecological communities of interacting organisms within their hosts, and there is growing interest in the health implications of such pathogen interactions. Although community ecology approaches have been used to identify pathogen interactions at the within-host scale, methodologies enabling robust identification of interactions from population-scale data such as that available from health authorities are lacking. To address this gap, we developed a statistical framework that jointly identifies interactions between multiple viruses from contemporaneous non-stationary infection time series. Our conceptual approach is derived from a Bayesian multivariate disease mapping framework. Importantly, our approach captures within- and between-year dependencies in infection risk while controlling for confounding factors such as seasonality, demographics and infection frequencies, allowing genuine pathogen interactions to be distinguished from simple correlations. We validated our framework using a broad range of synthetic data. We then applied it to diagnostic data available for five respiratory viruses co-circulating in a major urban population between 2005 and 2013: adenovirus, human coronavirus, human metapneumovirus, influenza B virus and respiratory syncytial virus. We found positive and negative covariances indicative of epidemiological interactions among specific virus pairs. This statistical framework enables a community ecology perspective to be applied to infectious disease epidemiology with important utility for public health planning and preparedness.",2019 Dec 13,"['Mair, Colette', 'Nickbakhsh, Sema', 'Reeve, Richard', 'McMenamin, Jim', 'Reynolds, Arlene', 'Gunson, Rory N.', 'Murcia, Pablo R.', 'Matthews, Louise']",PLoS Comput Biol,,,False
3881c1624df0b25cf7e9b0c6a7bd934b169de3f9,PMC,In Vivo Activity of Amodiaquine against Ebola Virus Infection,http://dx.doi.org/10.1038/s41598-019-56481-0,PMC6934550,31882748,CC BY,"During the Ebola virus disease (EVD) epidemic in Western Africa (2013‒2016), antimalarial treatment was administered to EVD patients due to the high coexisting malaria burden in accordance with World Health Organization guidelines. In an Ebola treatment center in Liberia, EVD patients receiving the combination antimalarial artesunate-amodiaquine had a lower risk of death compared to those treated with artemether-lumefantrine. As artemether and artesunate are derivatives of artemisinin, the beneficial anti-Ebola virus (EBOV) effect observed could possibly be attributed to the change from lumefantrine to amodiaquine. Amodiaquine is a widely used antimalarial in the countries that experience outbreaks of EVD and, therefore, holds promise as an approved drug that could be repurposed for treating EBOV infections. We investigated the potential anti-EBOV effect of amodiaquine in a well-characterized nonhuman primate model of EVD. Using a similar 3-day antimalarial dosing strategy as for human patients, plasma concentrations of amodiaquine in healthy animals were similar to those found in humans. However, the treatment regimen did not result in a survival benefit or decrease of disease signs in EBOV-infected animals. While amodiaquine on its own failed to demonstrate efficacy, we cannot exclude potential therapeutic value of amodiaquine when used in combination with artesunate or another antiviral.",2019 Dec 27,"['DeWald, Lisa Evans', 'Johnson, Joshua C.', 'Gerhardt, Dawn M.', 'Torzewski, Lisa M.', 'Postnikova, Elena', 'Honko, Anna N.', 'Janosko, Krisztina', 'Huzella, Louis', 'Dowling, William E.', 'Eakin, Ann E.', 'Osborn, Blaire L.', 'Gahagen, Janet', 'Tang, Liang', 'Green, Carol E.', 'Mirsalis, Jon C.', 'Holbrook, Michael R.', 'Jahrling, Peter B.', 'Dyall, Julie', 'Hensley, Lisa E.']",Sci Rep,,,False
93ad47dfe9435a6c7dac0510494626398fbe5ca2,PMC,In Vivo Activity of Amodiaquine against Ebola Virus Infection,http://dx.doi.org/10.1038/s41598-019-56481-0,PMC6934550,31882748,CC BY,"During the Ebola virus disease (EVD) epidemic in Western Africa (2013‒2016), antimalarial treatment was administered to EVD patients due to the high coexisting malaria burden in accordance with World Health Organization guidelines. In an Ebola treatment center in Liberia, EVD patients receiving the combination antimalarial artesunate-amodiaquine had a lower risk of death compared to those treated with artemether-lumefantrine. As artemether and artesunate are derivatives of artemisinin, the beneficial anti-Ebola virus (EBOV) effect observed could possibly be attributed to the change from lumefantrine to amodiaquine. Amodiaquine is a widely used antimalarial in the countries that experience outbreaks of EVD and, therefore, holds promise as an approved drug that could be repurposed for treating EBOV infections. We investigated the potential anti-EBOV effect of amodiaquine in a well-characterized nonhuman primate model of EVD. Using a similar 3-day antimalarial dosing strategy as for human patients, plasma concentrations of amodiaquine in healthy animals were similar to those found in humans. However, the treatment regimen did not result in a survival benefit or decrease of disease signs in EBOV-infected animals. While amodiaquine on its own failed to demonstrate efficacy, we cannot exclude potential therapeutic value of amodiaquine when used in combination with artesunate or another antiviral.",2019 Dec 27,"['DeWald, Lisa Evans', 'Johnson, Joshua C.', 'Gerhardt, Dawn M.', 'Torzewski, Lisa M.', 'Postnikova, Elena', 'Honko, Anna N.', 'Janosko, Krisztina', 'Huzella, Louis', 'Dowling, William E.', 'Eakin, Ann E.', 'Osborn, Blaire L.', 'Gahagen, Janet', 'Tang, Liang', 'Green, Carol E.', 'Mirsalis, Jon C.', 'Holbrook, Michael R.', 'Jahrling, Peter B.', 'Dyall, Julie', 'Hensley, Lisa E.']",Sci Rep,,,True
bd39af81a52b935dac2a4781c56bb2f501c8de29,PMC,A natural polymorphism in Zika virus NS2A protein responsible of virulence in mice,http://dx.doi.org/10.1038/s41598-019-56291-4,PMC6934710,31882898,CC BY,"Zika virus (ZIKV) infection is currently one of the major concerns in human public health due to its association with neurological disorders. Intensive effort has been implemented for the treatment of ZIKV, however there are not currently approved vaccines or antivirals available to combat ZIKV infection. In this sense, the identification of virulence factors associated with changes in ZIKV virulence could help to develop safe and effective countermeasures to treat ZIKV or to prevent future outbreaks. Here, we have compared the virulence of two related ZIKV strains from the recent outbreak in Brazil (2015), Rio Grande do Norte Natal (RGN) and Paraiba. In spite of both viruses being identified in the same period of time and region, significant differences in virulence and replication were observed using a validated mouse model of ZIKV infection. While ZIKV-RGN has a 50% mouse lethal dose (MLD(50)) of ~10(5) focus forming units (FFUs), ZIKV-Paraiba infection resulted in 100% of lethality with less than 10 FFUs. Combining deep-sequencing analysis and our previously described infectious ZIKV-RGN cDNA clone, we identified a natural polymorphism in the non-structural protein 2 A (NS2A) that increase the virulence of ZIKV. Moreover, results demonstrate that the single amino acid alanine to valine substitution at position 117 (A117V) in the NS2A was sufficient to convert the attenuated rZIKV-RGN in a virulent Paraiba-like virus (MLD(50) < 10 FFU). The mechanism of action was also evaluated and data indicate that substitution A117V in ZIKV NS2A protein reduces host innate immune responses and viral-induced apoptosis in vitro. Therefore, amino acid substitution A117V in ZIKV NS2A could be used as a genetic risk-assessment marker for future ZIKV outbreaks.",2019 Dec 27,"['Ávila-Pérez, Gines', 'Nogales, Aitor', 'Park, Jun-Gyu', 'Márquez-Jurado, Silvia', 'Iborra, Francisco J.', 'Almazan, Fernando', 'Martínez-Sobrido, Luis']",Sci Rep,,,False
a72473db86f1e26d0d1e6db3e7078a3536b9ba65,PMC,A natural polymorphism in Zika virus NS2A protein responsible of virulence in mice,http://dx.doi.org/10.1038/s41598-019-56291-4,PMC6934710,31882898,CC BY,"Zika virus (ZIKV) infection is currently one of the major concerns in human public health due to its association with neurological disorders. Intensive effort has been implemented for the treatment of ZIKV, however there are not currently approved vaccines or antivirals available to combat ZIKV infection. In this sense, the identification of virulence factors associated with changes in ZIKV virulence could help to develop safe and effective countermeasures to treat ZIKV or to prevent future outbreaks. Here, we have compared the virulence of two related ZIKV strains from the recent outbreak in Brazil (2015), Rio Grande do Norte Natal (RGN) and Paraiba. In spite of both viruses being identified in the same period of time and region, significant differences in virulence and replication were observed using a validated mouse model of ZIKV infection. While ZIKV-RGN has a 50% mouse lethal dose (MLD(50)) of ~10(5) focus forming units (FFUs), ZIKV-Paraiba infection resulted in 100% of lethality with less than 10 FFUs. Combining deep-sequencing analysis and our previously described infectious ZIKV-RGN cDNA clone, we identified a natural polymorphism in the non-structural protein 2 A (NS2A) that increase the virulence of ZIKV. Moreover, results demonstrate that the single amino acid alanine to valine substitution at position 117 (A117V) in the NS2A was sufficient to convert the attenuated rZIKV-RGN in a virulent Paraiba-like virus (MLD(50) < 10 FFU). The mechanism of action was also evaluated and data indicate that substitution A117V in ZIKV NS2A protein reduces host innate immune responses and viral-induced apoptosis in vitro. Therefore, amino acid substitution A117V in ZIKV NS2A could be used as a genetic risk-assessment marker for future ZIKV outbreaks.",2019 Dec 27,"['Ávila-Pérez, Gines', 'Nogales, Aitor', 'Park, Jun-Gyu', 'Márquez-Jurado, Silvia', 'Iborra, Francisco J.', 'Almazan, Fernando', 'Martínez-Sobrido, Luis']",Sci Rep,,,True
0b104ed7194e21c4ba47460db675b638b0d29bc4,PMC,Development and validation of an LC-MS/MS method for detection and quantification of in vivo derived metabolites of [Pyr(1)]apelin-13 in humans,http://dx.doi.org/10.1038/s41598-019-56157-9,PMC6934825,31882594,CC BY,"[Pyr(1)]apelin-13 is the predominant apelin peptide isoform in the human cardiovascular system and plasma. To date, few studies have investigated [Pyr(1)]apelin-13 metabolism in vivo in rats with no studies examining its stability in humans. We therefore aimed to develop an LC-MS/MS method for detection and quantification of intact [Pyr(1)]apelin-13 and have used this method to identify the metabolites generated in vivo in humans. [Pyr(1)]apelin-13 (135 nmol/min) was infused into six healthy human volunteers for 120 minutes and blood collected at time 0 and 120 minutes after infusion. Plasma was extracted in the presence of guanidine hydrochloride and analysed by LC-MS/MS. Here we report a highly sensitive, robust and reproducible method for quantification of intact [Pyr(1)]apelin-13 and its metabolites in human plasma. Using this method, we showed that the circulating concentration of intact peptide was 58.3 ± 10.5 ng/ml after 120 minutes infusion. We demonstrated for the first time that in humans, [Pyr(1)]apelin-13 was cleaved from both termini but the C-terminal was more susceptible to cleavage. Consequently, of the metabolites identified, [Pyr(1)]apelin-13((1–12)), [Pyr(1)]apelin-13((1–10)) and [Pyr(1)]apelin-13((1–6)) were the most abundant. These data suggest that apelin peptides designed for use as cardiovascular therapeutics, should include modifications that minimise C-terminal cleavage.",2019 Dec 27,"['Nyimanu, Duuamene', 'Kay, Richard G.', 'Sulentic, Petra', 'Kuc, Rhoda E.', 'Ambery, Philip', 'Jermutus, Lutz', 'Reimann, Frank', 'Gribble, Fiona M.', 'Cheriyan, Joseph', 'Maguire, Janet J.', 'Davenport, Anthony P.']",Sci Rep,,,True
ba755009e5f7330a8344f1b2dd8e65d54b8488e8,PMC,Prevalence and phylogenetic analysis of porcine diarrhea associated viruses in southern China from 2012 to 2018,http://dx.doi.org/10.1186/s12917-019-2212-2,PMC6935106,31881873,CC BY,"BACKGROUND: In China, large-scale outbreaks of severe diarrhea caused by viruses have occurred in pigs since late 2010. To investigate the prevalence and genetic evolution of diarrhea-associated viruses responsible for the outbreaks, a total of 2987 field diarrheal samples collected from 168 pig farms in five provinces in Southern China during 2012–2018 were tested. RESULTS: Porcine epidemic diarrhea virus (PEDV) was most frequently detected virus with prevalence rates between 50.21 and 62.10% in samples, and 96.43% (162/168) in premises, respectively. Porcine deltacoronavirus (PDCoV) was the second prevalent virus with prevalence rates ranging from 19.62 to 29.19% in samples, and 70.24% (118/168) in premises, respectively. Both transmissible gastroenteritis virus (TGEV) and porcine rotavirus (PoRV) were detected at low prevalence rates of < 3% in samples and 10.12% in premises. In this study, we identified a newly emerged swine acute diarrhea syndrome coronavirus (SADS-CoV) in diarrheal samples of piglets from Fujian province in Southern China, and the prevalence rate of SADS-CoV was 10.29% (7/68). Co-infections of these diarrhea-associated viruses were common. The most frequent co-infection was PEDV with PDCoV, with an average detection rate of 12.72% (380/2987, ranging from 8.26–17.33%). Phylogenetic analysis revealed that PEDVs circulating in Southern China during the last 7 years were clustered with the variant strains of PEDV in genotype IIa. The most frequent mutations were present in the collagenase equivalent (COE) and epitope regions of the spike gene of the PEDVs currently circulating in the field. Genetic relationships of PDCoVs were closely related with Chinese strains, other than those present in the USA, South Korea, Thailand and Lao’s public. CONCLUSIONS: The findings of this study indicated that variant PEDV, PDCoV, and SADS-CoV were leading etiologic agents of porcine diarrhea, and either mono-infections or co-infections of pathogenic enteric CoVs were common in pigs in Southern China during 2012–2018. Thus, significant attention should be paid in order to effectively prevent and control porcine viral diarrhea.",2019 Dec 27,"['Zhang, Fanfan', 'Luo, Suxian', 'Gu, Jun', 'Li, Zhiquan', 'Li, Kai', 'Yuan, Weifeng', 'Ye, Yu', 'Li, Hao', 'Ding, Zhen', 'Song, Deping', 'Tang, Yuxin']",BMC Vet Res,,,True
6c4fd19f82c72d0d52f0de8c0290f522646c6da7,PMC,"Zoonotic parasites of dromedary camels: so important, so ignored",http://dx.doi.org/10.1186/s13071-019-3863-3,PMC6935189,31881926,CC BY,"With a global population of about 35 million in 47 countries, dromedary camels play a crucial role in the economy of many marginal, desert areas of the world where they survive under harsh conditions. Nonetheless, there is scarce knowledge regarding camelsʼ parasite fauna which can reduce their milk and meat productions. In addition, only scattered information is available about zoonotic parasites transmitted to humans via contamination (e.g. Cryptosporidium spp., Giardia duodenalis, Balantidium coli, Blastocystis spp. and Enterocytozoon bieneusi), as foodborne infections (e.g. Toxoplasma gondii, Trichinella spp. and Linguatula serrata) or by arthropod vectors (Trypanosoma spp.). Herein, we draw attention of the scientific community and health policy-making organizations to the role camels play in the epidemiology of parasitic zoonotic diseases also in the view of an increase in their farming in desert areas worldwide. [Image: see text]",2019 Dec 27,"['Sazmand, Alireza', 'Joachim, Anja', 'Otranto, Domenico']",Parasit Vectors,,,True
9a30f5474e774545d4d1a2af333c6cbaf64cda4c,PMC,Microbial genomes from non-human primate gut metagenomes expand the primate-associated bacterial tree of life with over 1000 novel species,http://dx.doi.org/10.1186/s13059-019-1923-9,PMC6935492,31883524,CC BY,"BACKGROUND: Humans have coevolved with microbial communities to establish a mutually advantageous relationship that is still poorly characterized and can provide a better understanding of the human microbiome. Comparative metagenomic analysis of human and non-human primate (NHP) microbiomes offers a promising approach to study this symbiosis. Very few microbial species have been characterized in NHP microbiomes due to their poor representation in the available cataloged microbial diversity, thus limiting the potential of such comparative approaches. RESULTS: We reconstruct over 1000 previously uncharacterized microbial species from 6 available NHP metagenomic cohorts, resulting in an increase of the mappable fraction of metagenomic reads by 600%. These novel species highlight that almost 90% of the microbial diversity associated with NHPs has been overlooked. Comparative analysis of this new catalog of taxa with the collection of over 150,000 genomes from human metagenomes points at a limited species-level overlap, with only 20% of microbial candidate species in NHPs also found in the human microbiome. This overlap occurs mainly between NHPs and non-Westernized human populations and NHPs living in captivity, suggesting that host lifestyle plays a role comparable to host speciation in shaping the primate intestinal microbiome. Several NHP-specific species are phylogenetically related to human-associated microbes, such as Elusimicrobia and Treponema, and could be the consequence of host-dependent evolutionary trajectories. CONCLUSIONS: The newly reconstructed species greatly expand the microbial diversity associated with NHPs, thus enabling better interrogation of the primate microbiome and empowering in-depth human and non-human comparative and co-diversification studies.",2019 Dec 28,"['Manara, Serena', 'Asnicar, Francesco', 'Beghini, Francesco', 'Bazzani, Davide', 'Cumbo, Fabio', 'Zolfo, Moreno', 'Nigro, Eleonora', 'Karcher, Nicolai', 'Manghi, Paolo', 'Metzger, Marisa Isabell', 'Pasolli, Edoardo', 'Segata, Nicola']",Genome Biol,,,False
76aaa8d5b23ef9b7fd9cdf457054eee85a2d539a,PMC,Microbial genomes from non-human primate gut metagenomes expand the primate-associated bacterial tree of life with over 1000 novel species,http://dx.doi.org/10.1186/s13059-019-1923-9,PMC6935492,31883524,CC BY,"BACKGROUND: Humans have coevolved with microbial communities to establish a mutually advantageous relationship that is still poorly characterized and can provide a better understanding of the human microbiome. Comparative metagenomic analysis of human and non-human primate (NHP) microbiomes offers a promising approach to study this symbiosis. Very few microbial species have been characterized in NHP microbiomes due to their poor representation in the available cataloged microbial diversity, thus limiting the potential of such comparative approaches. RESULTS: We reconstruct over 1000 previously uncharacterized microbial species from 6 available NHP metagenomic cohorts, resulting in an increase of the mappable fraction of metagenomic reads by 600%. These novel species highlight that almost 90% of the microbial diversity associated with NHPs has been overlooked. Comparative analysis of this new catalog of taxa with the collection of over 150,000 genomes from human metagenomes points at a limited species-level overlap, with only 20% of microbial candidate species in NHPs also found in the human microbiome. This overlap occurs mainly between NHPs and non-Westernized human populations and NHPs living in captivity, suggesting that host lifestyle plays a role comparable to host speciation in shaping the primate intestinal microbiome. Several NHP-specific species are phylogenetically related to human-associated microbes, such as Elusimicrobia and Treponema, and could be the consequence of host-dependent evolutionary trajectories. CONCLUSIONS: The newly reconstructed species greatly expand the microbial diversity associated with NHPs, thus enabling better interrogation of the primate microbiome and empowering in-depth human and non-human comparative and co-diversification studies.",2019 Dec 28,"['Manara, Serena', 'Asnicar, Francesco', 'Beghini, Francesco', 'Bazzani, Davide', 'Cumbo, Fabio', 'Zolfo, Moreno', 'Nigro, Eleonora', 'Karcher, Nicolai', 'Manghi, Paolo', 'Metzger, Marisa Isabell', 'Pasolli, Edoardo', 'Segata, Nicola']",Genome Biol,,,False
e633cc8cbce07eacd478bb25aa824872ad55c59d,PMC,Microbial genomes from non-human primate gut metagenomes expand the primate-associated bacterial tree of life with over 1000 novel species,http://dx.doi.org/10.1186/s13059-019-1923-9,PMC6935492,31883524,CC BY,"BACKGROUND: Humans have coevolved with microbial communities to establish a mutually advantageous relationship that is still poorly characterized and can provide a better understanding of the human microbiome. Comparative metagenomic analysis of human and non-human primate (NHP) microbiomes offers a promising approach to study this symbiosis. Very few microbial species have been characterized in NHP microbiomes due to their poor representation in the available cataloged microbial diversity, thus limiting the potential of such comparative approaches. RESULTS: We reconstruct over 1000 previously uncharacterized microbial species from 6 available NHP metagenomic cohorts, resulting in an increase of the mappable fraction of metagenomic reads by 600%. These novel species highlight that almost 90% of the microbial diversity associated with NHPs has been overlooked. Comparative analysis of this new catalog of taxa with the collection of over 150,000 genomes from human metagenomes points at a limited species-level overlap, with only 20% of microbial candidate species in NHPs also found in the human microbiome. This overlap occurs mainly between NHPs and non-Westernized human populations and NHPs living in captivity, suggesting that host lifestyle plays a role comparable to host speciation in shaping the primate intestinal microbiome. Several NHP-specific species are phylogenetically related to human-associated microbes, such as Elusimicrobia and Treponema, and could be the consequence of host-dependent evolutionary trajectories. CONCLUSIONS: The newly reconstructed species greatly expand the microbial diversity associated with NHPs, thus enabling better interrogation of the primate microbiome and empowering in-depth human and non-human comparative and co-diversification studies.",2019 Dec 28,"['Manara, Serena', 'Asnicar, Francesco', 'Beghini, Francesco', 'Bazzani, Davide', 'Cumbo, Fabio', 'Zolfo, Moreno', 'Nigro, Eleonora', 'Karcher, Nicolai', 'Manghi, Paolo', 'Metzger, Marisa Isabell', 'Pasolli, Edoardo', 'Segata, Nicola']",Genome Biol,,,True
58657873c0bc33b6cbd816292e2d239228cde3a0,PMC,Metagenomic Nanopore Sequencing of Influenza Virus Direct from Clinical Respiratory Samples,http://dx.doi.org/10.1128/JCM.00963-19,PMC6935926,31666364,CC BY,"Influenza is a major global public health threat as a result of its highly pathogenic variants, large zoonotic reservoir, and pandemic potential. Metagenomic viral sequencing offers the potential for a diagnostic test for influenza virus which also provides insights on transmission, evolution, and drug resistance and simultaneously detects other viruses. We therefore set out to apply the Oxford Nanopore Technologies sequencing method to metagenomic sequencing of respiratory samples. We generated influenza virus reads down to a limit of detection of 10(2) to 10(3) genome copies/ml in pooled samples, observing a strong relationship between the viral titer and the proportion of influenza virus reads (P = 4.7 × 10(−5)). Applying our methods to clinical throat swabs, we generated influenza virus reads for 27/27 samples with mid-to-high viral titers (cycle threshold [C(T)] values, <30) and 6/13 samples with low viral titers (C(T) values, 30 to 40). No false-positive reads were generated from 10 influenza virus-negative samples. Thus, Nanopore sequencing operated with 83% sensitivity (95% confidence interval [CI], 67 to 93%) and 100% specificity (95% CI, 69 to 100%) compared to the current diagnostic standard. Coverage of full-length virus was dependent on sample composition, being negatively influenced by increased host and bacterial reads. However, at high influenza virus titers, we were able to reconstruct >99% complete sequences for all eight gene segments. We also detected a human coronavirus coinfection in one clinical sample. While further optimization is required to improve sensitivity, this approach shows promise for the Nanopore platform to be used in the diagnosis and genetic analysis of influenza virus and other respiratory viruses.",2019 Dec 23,"['Lewandowski, Kuiama', 'Xu, Yifei', 'Pullan, Steven T.', 'Lumley, Sheila F.', 'Foster, Dona', 'Sanderson, Nicholas', 'Vaughan, Alison', 'Morgan, Marcus', 'Bright, Nicole', 'Kavanagh, James', 'Vipond, Richard', 'Carroll, Miles', 'Marriott, Anthony C.', 'Gooch, Karen E.', 'Andersson, Monique', 'Jeffery, Katie', 'Peto, Timothy E. A.', 'Crook, Derrick W.', 'Walker, A. Sarah', 'Matthews, Philippa C.']",J Clin Microbiol,,,True
269fd3356f8e79929e7684ee9a433f5685523b97,PMC,Metagenomic Nanopore Sequencing of Influenza Virus Direct from Clinical Respiratory Samples,http://dx.doi.org/10.1128/JCM.00963-19,PMC6935926,31666364,CC BY,"Influenza is a major global public health threat as a result of its highly pathogenic variants, large zoonotic reservoir, and pandemic potential. Metagenomic viral sequencing offers the potential for a diagnostic test for influenza virus which also provides insights on transmission, evolution, and drug resistance and simultaneously detects other viruses. We therefore set out to apply the Oxford Nanopore Technologies sequencing method to metagenomic sequencing of respiratory samples. We generated influenza virus reads down to a limit of detection of 10(2) to 10(3) genome copies/ml in pooled samples, observing a strong relationship between the viral titer and the proportion of influenza virus reads (P = 4.7 × 10(−5)). Applying our methods to clinical throat swabs, we generated influenza virus reads for 27/27 samples with mid-to-high viral titers (cycle threshold [C(T)] values, <30) and 6/13 samples with low viral titers (C(T) values, 30 to 40). No false-positive reads were generated from 10 influenza virus-negative samples. Thus, Nanopore sequencing operated with 83% sensitivity (95% confidence interval [CI], 67 to 93%) and 100% specificity (95% CI, 69 to 100%) compared to the current diagnostic standard. Coverage of full-length virus was dependent on sample composition, being negatively influenced by increased host and bacterial reads. However, at high influenza virus titers, we were able to reconstruct >99% complete sequences for all eight gene segments. We also detected a human coronavirus coinfection in one clinical sample. While further optimization is required to improve sensitivity, this approach shows promise for the Nanopore platform to be used in the diagnosis and genetic analysis of influenza virus and other respiratory viruses.",2019 Dec 23,"['Lewandowski, Kuiama', 'Xu, Yifei', 'Pullan, Steven T.', 'Lumley, Sheila F.', 'Foster, Dona', 'Sanderson, Nicholas', 'Vaughan, Alison', 'Morgan, Marcus', 'Bright, Nicole', 'Kavanagh, James', 'Vipond, Richard', 'Carroll, Miles', 'Marriott, Anthony C.', 'Gooch, Karen E.', 'Andersson, Monique', 'Jeffery, Katie', 'Peto, Timothy E. A.', 'Crook, Derrick W.', 'Walker, A. Sarah', 'Matthews, Philippa C.']",J Clin Microbiol,,,False
0d40afa4fc54a163858aeffbe43be47bf89b6f39,PMC,Development of therapeutic antibodies for the treatment of diseases,http://dx.doi.org/10.1186/s12929-019-0592-z,PMC6939334,31894001,CC BY,"It has been more than three decades since the first monoclonal antibody was approved by the United States Food and Drug Administration (US FDA) in 1986, and during this time, antibody engineering has dramatically evolved. Current antibody drugs have increasingly fewer adverse effects due to their high specificity. As a result, therapeutic antibodies have become the predominant class of new drugs developed in recent years. Over the past five years, antibodies have become the best-selling drugs in the pharmaceutical market, and in 2018, eight of the top ten bestselling drugs worldwide were biologics. The global therapeutic monoclonal antibody market was valued at approximately US$115.2 billion in 2018 and is expected to generate revenue of $150 billion by the end of 2019 and $300 billion by 2025. Thus, the market for therapeutic antibody drugs has experienced explosive growth as new drugs have been approved for treating various human diseases, including many cancers, autoimmune, metabolic and infectious diseases. As of December 2019, 79 therapeutic mAbs have been approved by the US FDA, but there is still significant growth potential. This review summarizes the latest market trends and outlines the preeminent antibody engineering technologies used in the development of therapeutic antibody drugs, such as humanization of monoclonal antibodies, phage display, the human antibody mouse, single B cell antibody technology, and affinity maturation. Finally, future applications and perspectives are also discussed.",2020 Jan 2,"['Lu, Ruei-Min', 'Hwang, Yu-Chyi', 'Liu, I-Ju', 'Lee, Chi-Chiu', 'Tsai, Han-Zen', 'Li, Hsin-Jung', 'Wu, Han-Chung']",J Biomed Sci,,,True
3ca853dca7e2037fb95acf0b90ce59c9776979b1,PMC,Prevalence of Pathogens Related to Bovine Respiratory Disease Before and After Transportation in Beef Steers: Preliminary Results,http://dx.doi.org/10.3390/ani9121093,PMC6940923,31817737,CC BY,"SIMPLE SUMMARY: Bovine respiratory disease (BRD) affects the lower respiratory tract of cattle, causing high mortality. The syndrome has a multifactorial etiology and transport seems to favor pathogen proliferation. This study investigated the prevalence of different pathogens involved in BRD, in the nasal microbiota of beef steers collected before and after a long-distance journey. A total of 56 Limousine animals were included, travelling in three different shipments, on the same route from France to southern Italy in a semitrailer, on three different days from February to April. Prior to shipment (T0) and four days after arrival (T1), two deep nasopharyngeal swabs (DNS)/steer were collected and tested by bimolecular analysis. Neither bovine viral diarrhea virus (BVDV) nor bovine herpesvirus type 1 (BoHV-1) were detected. A higher prevalence of Histophilus somni was observed in the DNS collected during the third shipment in comparison with those registered during the first and the second one, probably due to a higher prevalence at departure. Conversely, the prevalence of bovine coronavirus, bovine respiratory syncytial virus, Mannheimia haemolytica, Mycoplasma bovis and Pasteurella multocida was higher on arrival in comparison with departure, confirming data reported in the literature. Overall, there were nasal microbiota changes in beef steers, with an increase in the prevalence of pathogens associated with BRD after travelling. ABSTRACT: Bovine respiratory disease (BRD) is a serious health and economic problem in the beef industry, which is often associated with transportation and caused by different pathogens. The prevalence of bovine herpesvirus type 1 (BoHV-1), bovine adenovirus (BAdV), bovine viral diarrhea virus (BVDV), bovine coronavirus (BCoV), bovine respiratory syncytial virus (BRSV), bovine parainfluenza virus (BPiV), Pasteurella multocida, Mannheimia haemolytica, Histophilus somni, Mycoplasma bovis, in the nasal microbiota of beef steers before and after the same long-distance journey from France to southern Italy was documented. Fifty-six Limousine animals of three different shipments, travelling on three different days from February to April, were included. Prior to shipment (T0) and four days after arrival (T1), two DNS/animal were collected and tested by Real Time quantitative PCR (qPCR). Univariate logistic regression was carried out, considering time and day as fixed factors and the outcome of qPCR for each pathogen as a dependent categorical dichotomous variable (positive/negative, 1/0). The fact that the number of H. somni positive animals were found to be higher in the third shipment than the first and second one, indicating that this pathogen was already present before loading, is relevant. The prevalence of BCoV, BRSV, M. haemolytica, M. bovis, P. multocida was higher at T1 than T0, suggesting that other factors, such as stress and the epidemiological status of the arrival farm, played a role. The tested animals were not treated before and after transport, and our results are in agreement with the current literature, supporting the hypothesis that the prevalence of pathogens related to BRD would increase after travelling, with an increased risk of pathogens shedding.",2019 Dec 6,"['Cirone, Francesco', 'Padalino, Barbara', 'Tullio, Daniele', 'Capozza, Paolo', 'Losurdo, Michele', 'Lanave, Gianvito', 'Pratelli, Annamaria']",Animals (Basel),,,True
71bad412cdb733dfe9f8d26251bda5ea331d20fa,PMC,Prevalence of Pathogens Related to Bovine Respiratory Disease Before and After Transportation in Beef Steers: Preliminary Results,http://dx.doi.org/10.3390/ani9121093,PMC6940923,31817737,CC BY,"SIMPLE SUMMARY: Bovine respiratory disease (BRD) affects the lower respiratory tract of cattle, causing high mortality. The syndrome has a multifactorial etiology and transport seems to favor pathogen proliferation. This study investigated the prevalence of different pathogens involved in BRD, in the nasal microbiota of beef steers collected before and after a long-distance journey. A total of 56 Limousine animals were included, travelling in three different shipments, on the same route from France to southern Italy in a semitrailer, on three different days from February to April. Prior to shipment (T0) and four days after arrival (T1), two deep nasopharyngeal swabs (DNS)/steer were collected and tested by bimolecular analysis. Neither bovine viral diarrhea virus (BVDV) nor bovine herpesvirus type 1 (BoHV-1) were detected. A higher prevalence of Histophilus somni was observed in the DNS collected during the third shipment in comparison with those registered during the first and the second one, probably due to a higher prevalence at departure. Conversely, the prevalence of bovine coronavirus, bovine respiratory syncytial virus, Mannheimia haemolytica, Mycoplasma bovis and Pasteurella multocida was higher on arrival in comparison with departure, confirming data reported in the literature. Overall, there were nasal microbiota changes in beef steers, with an increase in the prevalence of pathogens associated with BRD after travelling. ABSTRACT: Bovine respiratory disease (BRD) is a serious health and economic problem in the beef industry, which is often associated with transportation and caused by different pathogens. The prevalence of bovine herpesvirus type 1 (BoHV-1), bovine adenovirus (BAdV), bovine viral diarrhea virus (BVDV), bovine coronavirus (BCoV), bovine respiratory syncytial virus (BRSV), bovine parainfluenza virus (BPiV), Pasteurella multocida, Mannheimia haemolytica, Histophilus somni, Mycoplasma bovis, in the nasal microbiota of beef steers before and after the same long-distance journey from France to southern Italy was documented. Fifty-six Limousine animals of three different shipments, travelling on three different days from February to April, were included. Prior to shipment (T0) and four days after arrival (T1), two DNS/animal were collected and tested by Real Time quantitative PCR (qPCR). Univariate logistic regression was carried out, considering time and day as fixed factors and the outcome of qPCR for each pathogen as a dependent categorical dichotomous variable (positive/negative, 1/0). The fact that the number of H. somni positive animals were found to be higher in the third shipment than the first and second one, indicating that this pathogen was already present before loading, is relevant. The prevalence of BCoV, BRSV, M. haemolytica, M. bovis, P. multocida was higher at T1 than T0, suggesting that other factors, such as stress and the epidemiological status of the arrival farm, played a role. The tested animals were not treated before and after transport, and our results are in agreement with the current literature, supporting the hypothesis that the prevalence of pathogens related to BRD would increase after travelling, with an increased risk of pathogens shedding.",2019 Dec 6,"['Cirone, Francesco', 'Padalino, Barbara', 'Tullio, Daniele', 'Capozza, Paolo', 'Losurdo, Michele', 'Lanave, Gianvito', 'Pratelli, Annamaria']",Animals (Basel),,,False
287daad100931cefff81e066860bac399a008cbb,PMC,Therapeutic applications of nucleic acid aptamers in microbial infections,http://dx.doi.org/10.1186/s12929-019-0611-0,PMC6941257,31900238,CC BY,"Today, the treatment of bacterial infections is a major challenge, due to growing rate of multidrug-resistant bacteria, complication of treatment and increased healthcare costs. Moreover, new treatments for bacterial infections are limited. Oligonucleotide aptamers are single stranded DNAs or RNAs with target-selective high-affinity feature, which considered as nucleic acid-based affinity ligands, replacing monoclonal antibodies. The aptamer-based systems have been found to be talented tools in the treatment of microbial infections, regarding their promising anti-biofilm and antimicrobial activities; they can reduce or inhibit the effects of bacterial toxins, and inhibit pathogen invasion to immune cell, as well as they can be used in drug delivery systems. The focus of this review is on the therapeutic applications of aptamers in infections. In this regard, an introduction of infections and related challenges were presented, first. Then, aptamer definition and selection, with a brief history of aptamers development against various pathogens and toxins were reviewed. Diverse strategies of aptamer application in drug delivery, as well as, the effect of aptamers on the immune system, as the main natural agents of human defense against pathogens, were also discussed. Finally, the future trends in clinical applications of this technology were discussed.",2020 Jan 3,"['Afrasiabi, Shima', 'Pourhajibagher, Maryam', 'Raoofian, Reza', 'Tabarzad, Maryam', 'Bahador, Abbas']",J Biomed Sci,,,True
434358e4287b4199d921096173504d113905b6af,PMC,Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia,http://dx.doi.org/10.1186/s12864-019-6400-z,PMC6941262,31898474,CC BY,"BACKGROUND: Human metapneumovirus (HMPV) is an important cause of acute respiratory illness in young children. Whole genome sequencing enables better identification of transmission events and outbreaks, which is not always possible with sub-genomic sequences. RESULTS: We report a 2-reaction amplicon-based next generation sequencing method to determine the complete genome sequences of five HMPV strains, representing three subgroups (A2, B1 and B2), directly from clinical samples. In addition to reporting five novel HMPV genomes from Africa we examined genetic diversity and sequence patterns of publicly available HMPV genomes. We found that the overall nucleotide sequence identity was 71.3 and 80% for HMPV group A and B, respectively, the diversity between HMPV groups was greater at amino acid level for SH and G surface protein genes, and multiple subgroups co-circulated in various countries. Comparison of sequences between HMPV groups revealed variability in G protein length (219 to 241 amino acids) due to changes in the stop codon position. Genome-wide phylogenetic analysis showed congruence with the individual gene sequence sets except for F and M2 genes. CONCLUSION: This is the first genomic characterization of HMPV genomes from African patients.",2020 Jan 2,"['Kamau, Everlyn', 'Oketch, John W.', 'de Laurent, Zaydah R.', 'Phan, My V. T.', 'Agoti, Charles N.', 'Nokes, D. James', 'Cotten, Matthew']",BMC Genomics,,,False
94e5ba219fbf64f0e98ee34d3c7f10ce55d8d0d8,PMC,Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia,http://dx.doi.org/10.1186/s12864-019-6400-z,PMC6941262,31898474,CC BY,"BACKGROUND: Human metapneumovirus (HMPV) is an important cause of acute respiratory illness in young children. Whole genome sequencing enables better identification of transmission events and outbreaks, which is not always possible with sub-genomic sequences. RESULTS: We report a 2-reaction amplicon-based next generation sequencing method to determine the complete genome sequences of five HMPV strains, representing three subgroups (A2, B1 and B2), directly from clinical samples. In addition to reporting five novel HMPV genomes from Africa we examined genetic diversity and sequence patterns of publicly available HMPV genomes. We found that the overall nucleotide sequence identity was 71.3 and 80% for HMPV group A and B, respectively, the diversity between HMPV groups was greater at amino acid level for SH and G surface protein genes, and multiple subgroups co-circulated in various countries. Comparison of sequences between HMPV groups revealed variability in G protein length (219 to 241 amino acids) due to changes in the stop codon position. Genome-wide phylogenetic analysis showed congruence with the individual gene sequence sets except for F and M2 genes. CONCLUSION: This is the first genomic characterization of HMPV genomes from African patients.",2020 Jan 2,"['Kamau, Everlyn', 'Oketch, John W.', 'de Laurent, Zaydah R.', 'Phan, My V. T.', 'Agoti, Charles N.', 'Nokes, D. James', 'Cotten, Matthew']",BMC Genomics,,,False
60659e38c7b4dc4c37cbefd717209369298e9f92,PMC,Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia,http://dx.doi.org/10.1186/s12864-019-6400-z,PMC6941262,31898474,CC BY,"BACKGROUND: Human metapneumovirus (HMPV) is an important cause of acute respiratory illness in young children. Whole genome sequencing enables better identification of transmission events and outbreaks, which is not always possible with sub-genomic sequences. RESULTS: We report a 2-reaction amplicon-based next generation sequencing method to determine the complete genome sequences of five HMPV strains, representing three subgroups (A2, B1 and B2), directly from clinical samples. In addition to reporting five novel HMPV genomes from Africa we examined genetic diversity and sequence patterns of publicly available HMPV genomes. We found that the overall nucleotide sequence identity was 71.3 and 80% for HMPV group A and B, respectively, the diversity between HMPV groups was greater at amino acid level for SH and G surface protein genes, and multiple subgroups co-circulated in various countries. Comparison of sequences between HMPV groups revealed variability in G protein length (219 to 241 amino acids) due to changes in the stop codon position. Genome-wide phylogenetic analysis showed congruence with the individual gene sequence sets except for F and M2 genes. CONCLUSION: This is the first genomic characterization of HMPV genomes from African patients.",2020 Jan 2,"['Kamau, Everlyn', 'Oketch, John W.', 'de Laurent, Zaydah R.', 'Phan, My V. T.', 'Agoti, Charles N.', 'Nokes, D. James', 'Cotten, Matthew']",BMC Genomics,,,False
f5ae3f66face323615df39d838e056ab5fcc98df,PMC,Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia,http://dx.doi.org/10.1186/s12864-019-6400-z,PMC6941262,31898474,CC BY,"BACKGROUND: Human metapneumovirus (HMPV) is an important cause of acute respiratory illness in young children. Whole genome sequencing enables better identification of transmission events and outbreaks, which is not always possible with sub-genomic sequences. RESULTS: We report a 2-reaction amplicon-based next generation sequencing method to determine the complete genome sequences of five HMPV strains, representing three subgroups (A2, B1 and B2), directly from clinical samples. In addition to reporting five novel HMPV genomes from Africa we examined genetic diversity and sequence patterns of publicly available HMPV genomes. We found that the overall nucleotide sequence identity was 71.3 and 80% for HMPV group A and B, respectively, the diversity between HMPV groups was greater at amino acid level for SH and G surface protein genes, and multiple subgroups co-circulated in various countries. Comparison of sequences between HMPV groups revealed variability in G protein length (219 to 241 amino acids) due to changes in the stop codon position. Genome-wide phylogenetic analysis showed congruence with the individual gene sequence sets except for F and M2 genes. CONCLUSION: This is the first genomic characterization of HMPV genomes from African patients.",2020 Jan 2,"['Kamau, Everlyn', 'Oketch, John W.', 'de Laurent, Zaydah R.', 'Phan, My V. T.', 'Agoti, Charles N.', 'Nokes, D. James', 'Cotten, Matthew']",BMC Genomics,,,True
5f1578a62c27bf79646c2ef894cc185b322c8b4f,PMC,Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-β1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial,http://dx.doi.org/10.1186/s13063-019-3846-x,PMC6942374,31900204,CC BY,"ABSTRACT: The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-β1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-β1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02845843. Registered on 27 July 2016.",2020 Jan 3,"['Arabi, Yaseen M.', 'Asiri, Ayed Y.', 'Assiri, Abdullah M.', 'Aziz Jokhdar, Hani A.', 'Alothman, Adel', 'Balkhy, Hanan H.', 'AlJohani, Sameera', 'Al Harbi, Shmeylan', 'Kojan, Suleiman', 'Al Jeraisy, Majed', 'Deeb, Ahmad M.', 'Memish, Ziad A.', 'Ghazal, Sameeh', 'Al Faraj, Sarah', 'Al-Hameed, Fahad', 'AlSaedi, Asim', 'Mandourah, Yasser', 'Al Mekhlafi, Ghaleb A.', 'Sherbeeni, Nisreen Murad', 'Elzein, Fatehi Elnour', 'Almotairi, Abdullah', 'Al Bshabshe, Ali', 'Kharaba, Ayman', 'Jose, Jesna', 'Al Harthy, Abdulrahman', 'Al Sulaiman, Mohammed', 'Mady, Ahmed', 'Fowler, Robert A.', 'Hayden, Frederick G.', 'Al-Dawood, Abdulaziz', 'Abdelzaher, Mohamed', 'Bajhmom, Wail', 'Hussein, Mohamed A.', None]",Trials,,,True
9c2aa72aa0640f5224c2663ae55c35f75b8889c6,PMC,Virus–Host Coevolution with a Focus on Animal and Human DNA Viruses,http://dx.doi.org/10.1007/s00239-019-09913-4,PMC6943099,31599342,CC BY,"Viruses have been infecting their host cells since the dawn of life, and this extremely long-term coevolution gave rise to some surprising consequences for the entire tree of life. It is hypothesised that viruses might have contributed to the formation of the first cellular life form, or that even the eukaryotic cell nucleus originates from an infection by a coated virus. The continuous struggle between viruses and their hosts to maintain at least a constant fitness level led to the development of an unceasing arms race, where weapons are often shuttled between the participants. In this literature review we try to give a short insight into some general consequences or traits of virus–host coevolution, and after this we zoom in to the viral clades of adenoviruses, herpesviruses, nucleo-cytoplasmic large DNA viruses, polyomaviruses and, finally, circoviruses.",2020 Oct 10,"['Kaján, Győző L.', 'Doszpoly, Andor', 'Tarján, Zoltán László', 'Vidovszky, Márton Z.', 'Papp, Tibor']",J Mol Evol,,,True
d6d7306eb3f303f7461ab6cab965ef0c5d179719,PMC,Risk perception and behavioral change during epidemics: Comparing models of individual and collective learning,http://dx.doi.org/10.1371/journal.pone.0226483,PMC6944362,31905206,CC BY,"Modern societies are exposed to a myriad of risks ranging from disease to natural hazards and technological disruptions. Exploring how the awareness of risk spreads and how it triggers a diffusion of coping strategies is prominent in the research agenda of various domains. It requires a deep understanding of how individuals perceive risks and communicate about the effectiveness of protective measures, highlighting learning and social interaction as the core mechanisms driving such processes. Methodological approaches that range from purely physics-based diffusion models to data-driven environmental methods rely on agent-based modeling to accommodate context-dependent learning and social interactions in a diffusion process. Mixing agent-based modeling with data-driven machine learning has become popularity. However, little attention has been paid to the role of intelligent learning in risk appraisal and protective decisions, whether used in an individual or a collective process. The differences between collective learning and individual learning have not been sufficiently explored in diffusion modeling in general and in agent-based models of socio-environmental systems in particular. To address this research gap, we explored the implications of intelligent learning on the gradient from individual to collective learning, using an agent-based model enhanced by machine learning. Our simulation experiments showed that individual intelligent judgement about risks and the selection of coping strategies by groups with majority votes were outperformed by leader-based groups and even individuals deciding alone. Social interactions appeared essential for both individual learning and group learning. The choice of how to represent social learning in an agent-based model could be driven by existing cultural and social norms prevalent in a modeled society.",2020 Jan 6,"['Abdulkareem, Shaheen A.', 'Augustijn, Ellen-Wien', 'Filatova, Tatiana', 'Musial, Katarzyna', 'Mustafa, Yaseen T.']",PLoS One,,,True
0391c13dbb9949494913c209424ed61d3a652753,PMC,Ultrasensitive haptoglobin biomarker detection based on amplified chemiluminescence of magnetite nanoparticles,http://dx.doi.org/10.1186/s12951-019-0569-9,PMC6945394,31910856,CC BY,"BACKGROUND: Haptoglobin is an acute-phase protein used as predicting diagnostic biomarker both in humans (i.e., diabetes, ovarian cancer, some neurological and cardiovascular disorders) and in animals (e.g., bovine mastitis). The latter is a frequent disease of dairy industry with staggering economical losses upon decreased milk production and increased health care costs. Early stage diagnosis of the associated diseases or inflammation onset is almost impossible by conventional analytical manners. RESULTS: The present study demonstrates a simple, rapid, and cost-effective label-free chemiluminescence bioassay based on magnetite nanoparticles (MNPs) for sensitive detection of haptoglobin by employing the specific interaction of hemoglobin-modified MNPs. The resulting haptoglobin-hemoglobin complex inhibits the peroxidase-like activity of luminol/H(2)O(2)-hemoglobin-MNPs sensing scheme and reduces the chemiluminescence intensities correspondingly to the innate haptoglobin concentrations. Quantitative detection of bovine haptoglobin was obtained within the range of 1 pg mL(−1) to 1 µg mL(−1), while presenting 0.89 pg mL(−1) limit of detection. Moreover, the influence of causative pathogenic bacteria (i.e., Streptococcus dysgalactiae and Escherichia coli) and somatic cell counts (depicting healthy, sub-clinical and clinical mastitis) on the emitted chemiluminescence radiation were established. The presented bioassay quantitative performances correspond with a standardized assay kit in differentiating dissimilar milk qualities. CONCLUSIONS: Overall, the main advantage of the presented sensing concept is the ability to detect haptoglobin, at clinically relevant concentrations within real milk samples for early bio-diagnostic detection of mastitis and hence adjusting the precise treatment, potentially initiating a positive influence on animals’ individual health and hence on dairy farms economy.",2020 Jan 7,"['Nirala, Narsingh R.', 'Harel, Yifat', 'Lellouche, Jean-Paul', 'Shtenberg, Giorgi']",J Nanobiotechnology,,,True
879387ff0282d3823d01dded6b50b383e1741342,PMC,Mating strategy is determinant of adenovirus prevalence in European bats,http://dx.doi.org/10.1371/journal.pone.0226203,PMC6946596,31910439,CC BY,"Adenoviruses are double-strained DNA viruses found in a great number of vertebrates, including humans. In order to understand their transmission dynamics, it is crucial, even from a human health perspective, to investigate how host traits influence their prevalence. Bats are important reservoirs for adenoviruses, and here we use the results of recent screenings in Western Europe to evaluate the association between characteristic traits of bat species and their probability of hosting adenoviruses, taking into account their phylogenetic relationships. Across species, we found an important phylogenetic component in the presence of adenoviruses and mating strategy as the most determinant factor conditioning the prevalence of adenoviruses across bat species. Contrary to other more stable mating strategies (e.g. harems), swarming could hinder transmission of adenoviruses since this strategy implies that contacts between individuals are too short. Alternatively, bat species with more promiscuous behavior may develop a stronger immune system. Outstandingly high prevalence of adenoviruses was reported for the Iberian species Pipistrellus pygmaeus, P. kuhlii and Nyctalus lasiopterus and we found that in the latter, males were more likely to be infected by adenoviruses than females, due to the immunosuppressing consequence of testosterone during the mating season. As a general trend across species, we found that the number of adenoviruses positive individuals was different across localities and that the difference in prevalence between populations was correlated with their geographic distances for two of the three studied bat species (P. pygmaeus and P.kuhlii). These results increase our knowledge about the transmission mechanisms of adenoviruses.",2020 Jan 7,"['Rossetto, Federica', 'Iglesias-Caballero, Maria', 'Liedtke, H. Christoph', 'Gomez-Mestre, Ivan', 'Berciano, Jose M.', 'Pérez-Suárez, Gonzalo', 'de Paz, Oscar', 'Ibáñez, Carlos', 'Echevarría, Juan E.', 'Casas, Inmaculada', 'Juste, Javier']",PLoS One,,,True
1ce01bfd8909920c3da397b92d9803389f043268,PMC,RNA-Dependent RNA Polymerase Speed and Fidelity are not the Only Determinants of the Mechanism or Efficiency of Recombination,http://dx.doi.org/10.3390/genes10120968,PMC6947342,31775299,CC BY,"Using the RNA-dependent RNA polymerase (RdRp) from poliovirus (PV) as our model system, we have shown that Lys-359 in motif-D functions as a general acid in the mechanism of nucleotidyl transfer. A K359H (KH) RdRp derivative is slow and faithful relative to wild-type enzyme. In the context of the KH virus, RdRp-coding sequence evolves, selecting for the following substitutions: I331F (IF, motif-C) and P356S (PS, motif-D). We have evaluated IF-KH, PS-KH, and IF-PS-KH viruses and enzymes. The speed and fidelity of each double mutant are equivalent. Each exhibits a unique recombination phenotype, with IF-KH being competent for copy-choice recombination and PS-KH being competent for forced-copy-choice recombination. Although the IF-PS-KH RdRp exhibits biochemical properties within twofold of wild type, the virus is impaired substantially for recombination in cells. We conclude that there are biochemical properties of the RdRp in addition to speed and fidelity that determine the mechanism and efficiency of recombination. The interwoven nature of speed, fidelity, the undefined property suggested here, and recombination makes it impossible to attribute a single property of the RdRp to fitness. However, the derivatives described here may permit elucidation of the importance of recombination on the fitness of the viral population in a background of constant polymerase speed and fidelity.",2019 Nov 25,"['Kim, Hyejeong', 'Ellis, Victor D.', 'Woodman, Andrew', 'Zhao, Yan', 'Arnold, Jamie J.', 'Cameron, Craig E.']",Genes (Basel),,,True
095424c03a6e78279e47488552d961bc328f9c84,PMC,"Preclinical evaluation of AT-527, a novel guanosine nucleotide prodrug with potent, pan-genotypic activity against hepatitis C virus",http://dx.doi.org/10.1371/journal.pone.0227104,PMC6949113,31914458,CC BY,"Despite the availability of highly effective direct-acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) infections, sustained viral response (SVR) rates remain suboptimal for difficult-to-treat patient populations such as those with HCV genotype 3, cirrhosis or prior treatment experience, warranting development of more potent HCV replication antivirals. AT-527 is the hemi-sulfate salt of AT-511, a novel phosphoramidate prodrug of 2’-fluoro-2’-C-methylguanosine-5'-monophosphate that has potent in vitro activity against HCV. The EC(50) of AT-511, determined using HCV laboratory strains and clinical isolates with genotypes 1–5, ranged from 5–28 nM. The active 5'-triphosphate metabolite, AT-9010, specifically inhibited the HCV RNA-dependent RNA polymerase. AT-511 did not inhibit the replication of other selected RNA or DNA viruses in vitro. AT-511 was approximately 10-fold more active than sofosbuvir (SOF) against a panel of laboratory strains and clinical isolates of HCV genotypes 1–5 and remained fully active against S282T resistance-associated variants, with up to 58-fold more potency than SOF. In vitro, AT-511 did not inhibit human DNA polymerases or elicit cytotoxicity or mitochondrial toxicity at concentrations up to 100 μM. Unlike the other potent guanosine analogs PSI-938 and PSI-661, no mutagenic O(6)-alkylguanine bases were formed when incubated with cytochrome P450 (CYP) 3A4, and AT-511 had IC(50) values ≥25 μM against a panel of CYP enzymes. In hepatocytes from multiple species, the active triphosphate was the predominant metabolite produced from the prodrug, with a half-life of 10 h in human hepatocytes. When given orally to rats and monkeys, AT-527 preferentially delivered high levels of AT-9010 in the liver in vivo. These favorable preclinical attributes support the ongoing clinical development of AT-527 and suggest that, when used in combination with an HCV DAA from a different class, AT-527 may increase SVR rates, especially for difficult-to-treat patient populations, and could potentially shorten treatment duration for all patients.",2020 Jan 8,"['Good, Steven S.', 'Moussa, Adel', 'Zhou, Xiao-Jian', 'Pietropaolo, Keith', 'Sommadossi, Jean-Pierre']",PLoS One,,,True
e724e9c56dedc9430663c4eb447b1b0ec08133e6,PMC,Simian adenovirus vector production for early-phase clinical trials: A simple method applicable to multiple serotypes and using entirely disposable product-contact components,http://dx.doi.org/10.1016/j.vaccine.2019.04.056,PMC6949866,31047679,CC BY,"A variety of Good Manufacturing Practice (GMP) compliant processes have been reported for production of non-replicating adenovirus vectors, but important challenges remain. Most clinical development of adenovirus vectors now uses simian adenoviruses or rare human serotypes, whereas reported manufacturing processes mainly use serotypes such as AdHu5 which are of questionable relevance for clinical vaccine development. Many clinically relevant vaccine transgenes interfere with adenovirus replication, whereas most reported process development uses selected antigens or even model transgenes such as fluorescent proteins which cause little such interference. Processes are typically developed for a single adenovirus serotype – transgene combination, requiring extensive further optimization for each new vaccine. There is a need for rapid production platforms for small GMP batches of non-replicating adenovirus vectors for early-phase vaccine trials, particularly in preparation for response to emerging pathogen outbreaks. Such platforms must be robust to variation in the transgene, and ideally also capable of producing adenoviruses of more than one serotype. It is also highly desirable for such processes to be readily implemented in new facilities using commercially available single-use materials, avoiding the need for development of bespoke tools or cleaning validation, and for them to be readily scalable for later-stage studies. Here we report the development of such a process, using single-use stirred-tank bioreactors, a transgene-repressing HEK293 cell – promoter combination, and fully single-use filtration and ion exchange components. We demonstrate applicability of the process to candidate vaccines against rabies, malaria and Rift Valley fever, each based on a different adenovirus serotype. We compare performance of a range of commercially available ion exchange media, including what we believe to be the first published use of a novel media for adenovirus purification (NatriFlo® HD-Q, Merck). We demonstrate the need for minimal process individualization for each vaccine, and that the product fulfils regulatory quality expectations. Cell-specific yields are at the upper end of those previously reported in the literature, and volumetric yields are in the range 1 × 10(13) – 5 × 10(13) purified virus particles per litre of culture, such that a 2–4 L process is comfortably adequate to produce vaccine for early-phase trials. The process is readily transferable to any GMP facility with the capability for mammalian cell culture and aseptic filling of sterile products.",2019 Nov 8,"['Fedosyuk, Sofiya', 'Merritt, Thomas', 'Peralta-Alvarez, Marco Polo', 'Morris, Susan J', 'Lam, Ada', 'Laroudie, Nicolas', 'Kangokar, Anilkumar', 'Wright, Daniel', 'Warimwe, George M', 'Angell-Manning, Phillip', 'Ritchie, Adam J', 'Gilbert, Sarah C', 'Xenopoulos, Alex', 'Boumlic, Anissa', 'Douglas, Alexander D']",Vaccine,,,False
06f8316b5b1cd5f0737d5ada43c3dd9ebce27a91,PMC,"Caring for Tuberculosis Patients: Understanding the Plight of Nurses at a Regional Hospital in Limpopo Province, South Africa",http://dx.doi.org/10.3390/ijerph16244977,PMC6949926,31817829,CC BY,"Tuberculosis (TB) is a disease which is caused by a relatively large, non-motile, rod-shaped pathogen called Mycobacterium tuberculosis. TB is a major cause of illness and death worldwide, especially in Asia and Africa. Despite the fact that TB is a curable illness, the tragedy is that TB remains the biggest killer in the world as a single pathogen. The aim of this study was to determine the experiences of nurses caring for TB patients at a regional hospital in Limpopo Province, South Africa. Qualitative, exploratory, and descriptive designs were used. A non-probability purposive sampling method was used to select the participants. The personal experiences of six nurses with more than five years’ experience caring for TB patients at a regional hospital were explored, and it was guided by data saturation. Data were collected through in-depth individual interviews. Data were analyzed using Colaizzi’s method. Trustworthiness was ensured and ethical considerations were observed in this study. The research findings revealed six major themes from the raw data: challenges of the working environment, problems impacting on the quality of nursing care, fear, anxiety, stress and risk of contracting infection, nurses’ perceptions towards patients, support structure available in the hospital, and support needs for the nurses. Therefore, there is an urgent need to address the challenges experienced by nurses caring for communicable diseases through provision of a positive practice work environment.",2019 Dec 7,"['Matakanye, Hulisani', 'Ramathuba, Dorah U.', 'Tugli, Augustine K.']",Int J Environ Res Public Health,,,True
d408854267a5f3330fab52531265d9a38a91e60f,PMC,Feline Infectious Peritonitis as a Systemic Inflammatory Disease: Contribution of Liver and Heart to the Pathogenesis,http://dx.doi.org/10.3390/v11121144,PMC6949997,31835559,CC BY,"Feline infectious peritonitis (FIP) is a fatal immune-mediated disease of cats, induced by feline coronavirus (FCoV). A combination of as yet poorly understood host and viral factors combine to cause a minority of FCoV-infected cats to develop FIP. Clinicopathological features include fever, vasculitis, and serositis, with or without effusions; all of which indicate a pro-inflammatory state with cytokine release. As a result, primary immune organs, as well as circulating leukocytes, have thus far been of most interest in previous studies to determine the likely sources of these cytokines. Results have suggested that these tissues alone may not be sufficient to induce the observed inflammation. The current study therefore focussed on the liver and heart, organs with a demonstrated ability to produce cytokines and therefore with huge potential to exacerbate inflammatory processes. The IL-12:IL-10 ratio, a marker of the immune system’s inflammatory balance, was skewed towards the pro-inflammatory IL-12 in the liver of cats with FIP. Both organs were found to upregulate mRNA expression of the inflammatory triad of cytokines IL-1β, IL-6, and TNF-α in FIP. This amplifying step may be one of the missing links in the pathogenesis of this enigmatic disease.",2019 Dec 10,"['Malbon, Alexandra J', 'Fonfara, Sonja', 'Meli, Marina L', 'Hahn, Shelley', 'Egberink, Herman', 'Kipar, Anja']",Viruses,,,True
4bcdac71c12d45032dfb8c6753e7d94643a11283,PMC,A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice,http://dx.doi.org/10.3390/v11121149,PMC6950126,31835785,CC BY,"Sudan virus (SUDV) causes severe lethal hemorrhagic fever in humans and nonhuman primates. The most effective and economical way to protect against Sudan ebolavirus disease is prophylactic vaccination. However, there are no licensed vaccines to prevent SUDV infections. In this study, a bacterium-like particle (BLP)-based vaccine displaying the extracellular domain of the SUDV glycoprotein (eGP) was developed based on a gram-positive enhancer matrix-protein anchor (GEM-PA) surface display system. Expression of the recombinant GEM-displayed eGP (eGP-PA-GEM) was verified by Western blotting and immunofluorescence assays. The SUDV BLPs (SBLPs), which were mixed with Montanide ISA 201VG plus Poly (I:C) combined adjuvant, could induce high SUDV GP-specific IgG titers of up to 1:40,960 and robust virus-neutralizing antibody titers reached 1:460. The SBLP also elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. These data indicate that the SBLP subunit vaccine has the potential to be developed into a promising candidate vaccine against SUDV infections.",2019 Dec 11,"['Xu, Shengnan', 'Jiao, Cuicui', 'Jin, Hongli', 'Li, Wujian', 'Li, Entao', 'Cao, Zengguo', 'Shi, Zhikang', 'Yan, Feihu', 'Zhang, Shengnan', 'He, Hongbin', 'Chi, Hang', 'Feng, Na', 'Zhao, Yongkun', 'Gao, Yuwei', 'Yang, Songtao', 'Wang, Jianzhong', 'Wang, Hualei', 'Xia, Xianzhu']",Viruses,,,True
71f40deaea2448ea82b36aea4b91149e588c39c0,PMC,Identification of Nuclear Localization Signals in the ORF2 Protein of Porcine Circovirus Type 3,http://dx.doi.org/10.3390/v11121086,PMC6950156,31766638,CC BY,"Porcine circovirus type 3 (PCV3) contains two major open reading frames (ORFs) and the ORF2 gene encodes the major structural capsid protein. In this study, nuclear localization of ORF2 was demonstrated by fluorescence observation and subcellular fractionation assays in ORF2-transfected PK-15 cells. The subcellular localization of truncated ORF2 indicated that the 38 N-terminal amino acids were responsible for the nuclear localization of ORF2. The truncated and site-directed mutagenesis of this domain were constructed, and the results demonstrated that the basic amino acid residues at positions 8–32 were essential for the strict nuclear localization. The basic motifs (8)RRR-R-RRR(16) and (16)RRRHRRR(22) were further shown to be the key functional nucleolar localization signals that guide PCV3 ORF2 into nucleoli. Furthermore, sequence analysis showed that the amino acids of PCV3 nuclear localization signals were highly conserved. Overall, this study provides insight into the biological and functional characteristics of the PCV3 ORF2 protein.",2019 Nov 22,"['Mou, Chunxiao', 'Wang, Minmin', 'Pan, Shuonan', 'Chen, Zhenhai']",Viruses,,,True
21823032c216c8f7e08c918373d49518c68aaab1,PMC,A Comparative Analysis of Factors Influencing Two Outbreaks of Middle Eastern Respiratory Syndrome (MERS) in Saudi Arabia and South Korea,http://dx.doi.org/10.3390/v11121119,PMC6950189,31817037,CC BY,"In 2012, an emerging viral infection was identified in Saudi Arabia that subsequently spread to 27 additional countries globally, though cases may have occurred elsewhere. The virus was ultimately named Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV), and has been endemic in Saudi Arabia since 2012. As of September 2019, 2468 laboratory-confirmed cases with 851 associated deaths have occurred with a case fatality rate of 34.4%, according to the World Health Organization. An imported case of MERS occurred in South Korea in 2015, stimulating a multi-month outbreak. Several distinguishing factors emerge upon epidemiological and sociological analysis of the two outbreaks including public awareness of the MERS outbreak, and transmission and synchronization of governing healthcare bodies. South Korea implemented a stringent healthcare model that protected patients and healthcare workers alike through prevention and high levels of public information. In addition, many details about MERS-CoV virology, transmission, pathological progression, and even the reservoir, remain unknown. This paper aims to delineate the key differences between the two regional outbreaks from both a healthcare and personal perspective including differing hospital practices, information and public knowledge, cultural practices, and reservoirs, among others. Further details about differing emergency outbreak responses, public information, and guidelines put in place to protect hospitals and citizens could improve the outcome of future MERS outbreaks.",2019 Dec 3,"['Willman, Marnie', 'Kobasa, Darwyn', 'Kindrachuk, Jason']",Viruses,,,True
dafc5a833630d362e8ac97ce094a669204ef62e5,PMC,Development and Validation of a S1 Protein-Based ELISA for the Specific Detection of Antibodies against Equine Coronavirus,http://dx.doi.org/10.3390/v11121109,PMC6950238,31801275,CC BY,"Equine coronavirus (ECoV) is considered to be involved in enteric diseases in foals. Recently, several outbreaks of ECoV infection have also been reported in adult horses from the USA, France and Japan. Epidemiological studies of ECoV infection are still limited, and the seroprevalence of ECoV infection in Europe is unknown. In this study, an indirect enzyme-linked immunosorbent assay (ELISA) method utilizing ECoV spike S1 protein was developed in two formats, and further validated by analyzing 27 paired serum samples (acute and convalescent sera) from horses involved in an ECoV outbreak and 1084 sera of horses with unknown ECoV exposure. Both formats showed high diagnostic accuracy compared to virus neutralization (VN) assay. Receiver-operating characteristic (ROC) analyses were performed to determine the best cut-off values for both ELISA formats, assuming a test specificity of 99%. Employing the developed ELISA method, we detected seroconversion in 70.4% of horses from an ECoV outbreak. Among the 1084 horse sera, seropositivity varied from 25.9% (young horses) to 82.8% (adult horses) in Dutch horse populations. Further, sera of Icelandic horses were included in this study and a significant number of sera (62%) were found to be positive. Overall, the results demonstrated that the ECoV S1-based ELISA has reliable diagnostic performance compared to the VN assay and is a useful assay to support seroconversion in horses involved with ECoV outbreaks and to estimate ECoV seroprevalence in populations of horses.",2019 Nov 30,"['Zhao, Shan', 'Smits, Constance', 'Schuurman, Nancy', 'Barnum, Samantha', 'Pusterla, Nicola', 'van Kuppeveld, Frank', 'Bosch, Berend-Jan', 'van Maanen, Kees', 'Egberink, Herman']",Viruses,,,True
3727f751c9cf944c8e6ddf578f5644629ed50d45,PMC,Tilapia Lake Virus Does Not Hemagglutinate Avian and Piscine Erythrocytes and NH(4)Cl Does Not Inhibit Viral Replication In Vitro,http://dx.doi.org/10.3390/v11121152,PMC6950307,31842425,CC BY,"Tilapia lake virus (TiLV) is a negative-sense single-stranded RNA (-ssRNA) icosahedral virus classified to be the only member in the family Amnoonviridae. Although TiLV segment-1 shares homology with the influenza C virus PB1 and has four conserved motifs similar to influenza A, B, and C polymerases, it is unknown whether there are other properties shared between TiLV and orthomyxovirus. In the present study, we wanted to determine whether TiLV agglutinated avian and piscine erythrocytes, and whether its replication was inhibited by lysosomotropic agents, such as ammonium chloride (NH(4)Cl), as seen for orthomyxoviruses. Our findings showed that influenza virus strain A/Puerto Rico/8 (PR8) was able to hemagglutinate turkey (Meleagris gallopavo), Atlantic salmon (Salmo salar L), and Nile tilapia (Oreochromis niloticus) red blood cells (RBCs), while infectious salmon anemia virus (ISAV) only agglutinated Atlantic salmon, but not turkey or tilapia, RBCs. In contrast to PR8 and ISAV, TiLV did not agglutinate turkey, Atlantic salmon, or tilapia RBCs. qRT-PCR analysis showed that 30 mM NH(4)Cl, a basic lysosomotropic agent, neither inhibited nor enhanced TiLV replication in E-11 cells. There was no difference in viral quantities in the infected cells with or without NH(4)Cl treatment during virus adsorption or at 1, 2, and 3 h post-infection. Given that hemagglutinin proteins that bind RBCs also serve as ligands that bind host cells during virus entry leading to endocytosis in orthomyxoviruses, the data presented here suggest that TiLV may use mechanisms that are different from orthomyxoviruses for entry and replication in host cells. Therefore, future studies should seek to elucidate the mechanisms used by TiLV for entry into host cells and to determine its mode of replication in infected cells.",2019 Dec 12,"['Chengula, Augustino Alfred', 'Mutoloki, Stephen', 'Evensen, Øystein', 'Munang’andu, Hetron Mweemba']",Viruses,,,True
5367c37ddfee14aaa94c806703361f23e09caffd,PMC,Viral Diversity of Microbats within the South West Botanical Province of Western Australia,http://dx.doi.org/10.3390/v11121157,PMC6950384,31847282,CC BY,"Bats are known reservoirs of a wide variety of viruses that rarely result in overt clinical disease in the bat host. However, anthropogenic influences on the landscape and climate can change species assemblages and interactions, as well as undermine host-resilience. The cumulative result is a disturbance of bat–pathogen dynamics, which facilitate spillover events to sympatric species, and may threaten bat communities already facing synergistic stressors through ecological change. Therefore, characterisation of viral pathogens in bat communities provides important basal information to monitor and predict the emergence of diseases relevant to conservation and public health. This study used targeted molecular techniques, serological assays and next generation sequencing to characterise adenoviruses, coronaviruses and paramyxoviruses from 11 species of insectivorous bats within the South West Botanical Province of Western Australia. Phylogenetic analysis indicated complex ecological interactions including virus–host associations, cross-species infections, and multiple viral strains circulating concurrently within selected bat populations. Additionally, we describe the entire coding sequences for five alphacoronaviruses (representing four putative new species), and one novel adenovirus. Results indicate that viral burden (both prevalence and richness) is not homogeneous among species, with Chalinolobus gouldii identified as a key epidemiological element within the studied communities.",2019 Dec 13,"['Prada, Diana', 'Boyd, Victoria', 'Baker, Michelle L.', 'O’Dea, Mark', 'Jackson, Bethany']",Viruses,,,True
a4f95bc90ea589d614f0e2a70daf60fbd7d23c31,PMC,Antigenic and Pathogenic Characteristics of QX-Type Avian Infectious Bronchitis Virus Strains Isolated in Southwestern China,http://dx.doi.org/10.3390/v11121154,PMC6950461,31847269,CC BY,"The QX-type avian infectious bronchitis virus (IBV) is still a prevalent genotype in Southwestern China. To analyze the antigenicity and pathogenicity characteristics of the dominant genotype strains (QX-type), S1 gene sequence analysis, virus cross-neutralization tests, and pathogenicity test of eight QX-type IBV isolates were conducted. Sequence analysis showed that the nucleotide homology between the eight strains was high, but distantly related to H120 and 4/91 vaccine strains. Cross-neutralization tests showed that all eight strains isolated from 2015 and 2017 belonged to the same serotype, but exhibited antigenic variations over time. The pathogenicity test of the five QX-type IBV isolates showed that only three strains, CK/CH/SC/DYW/16, CK/CH/SC/MS/17, and CK/CH/SC/GH/15, had a high mortality rate with strong respiratory and renal pathogenicity, whereas CK/CH/SC/PZ/17 and CK/CH/SC/DYYJ/17 caused only mild clinical symptoms and tissue lesions. Our results indicate that the prevalent QX-type IBVs displayed antigenic variations and pathogenicity difference. These findings may provide reference for research on the evolution of IBV and vaccine preparation of infectious bronchitis (IB).",2019 Dec 13,"['Li, Shuyun', 'Du, Lijing', 'Xia, Jing', 'Du, Jiteng', 'You, Guojin', 'Wen, Yiping', 'Huang, Xiaobo', 'Zhao, Qing', 'Han, Xinfeng', 'Yan, Qigui', 'Wu, Rui', 'Cui, Min', 'Cao, Sanjie', 'Huang, Yong']",Viruses,,,True
3fd831d05b33dce248e4acee815f719ce3f979dc,PMC,Antigenic and Pathogenic Characteristics of QX-Type Avian Infectious Bronchitis Virus Strains Isolated in Southwestern China,http://dx.doi.org/10.3390/v11121154,PMC6950461,31847269,CC BY,"The QX-type avian infectious bronchitis virus (IBV) is still a prevalent genotype in Southwestern China. To analyze the antigenicity and pathogenicity characteristics of the dominant genotype strains (QX-type), S1 gene sequence analysis, virus cross-neutralization tests, and pathogenicity test of eight QX-type IBV isolates were conducted. Sequence analysis showed that the nucleotide homology between the eight strains was high, but distantly related to H120 and 4/91 vaccine strains. Cross-neutralization tests showed that all eight strains isolated from 2015 and 2017 belonged to the same serotype, but exhibited antigenic variations over time. The pathogenicity test of the five QX-type IBV isolates showed that only three strains, CK/CH/SC/DYW/16, CK/CH/SC/MS/17, and CK/CH/SC/GH/15, had a high mortality rate with strong respiratory and renal pathogenicity, whereas CK/CH/SC/PZ/17 and CK/CH/SC/DYYJ/17 caused only mild clinical symptoms and tissue lesions. Our results indicate that the prevalent QX-type IBVs displayed antigenic variations and pathogenicity difference. These findings may provide reference for research on the evolution of IBV and vaccine preparation of infectious bronchitis (IB).",2019 Dec 13,"['Li, Shuyun', 'Du, Lijing', 'Xia, Jing', 'Du, Jiteng', 'You, Guojin', 'Wen, Yiping', 'Huang, Xiaobo', 'Zhao, Qing', 'Han, Xinfeng', 'Yan, Qigui', 'Wu, Rui', 'Cui, Min', 'Cao, Sanjie', 'Huang, Yong']",Viruses,,,False
1cb0c02329d10e7513faabdc57113172591d5406,PMC,"Rapid, Unbiased PRRSV Strain Detection Using MinION Direct RNA Sequencing and Bioinformatics Tools",http://dx.doi.org/10.3390/v11121132,PMC6950593,31817886,CC BY,"Prompt detection and effective control of porcine reproductive and respiratory syndrome virus (PRRSV) during outbreaks is important given its immense adverse impact on the swine industry. However, the diagnostic process can be challenging due to the high genetic diversity and high mutation rate of PRRSV. A diagnostic method that can provide more detailed genetic information about pathogens is urgently needed. In this study, we evaluated the ability of Oxford Nanopore MinION direct RNA sequencing to generate a PRRSV whole genome sequence and detect and discriminate virus at the strain-level. A nearly full length PRRSV genome was successfully generated from raw sequence reads, achieving an accuracy of 96% after consensus genome generation. Direct RNA sequencing reliably detected the PRRSV strain present with an accuracy of 99.9% using as few as 5 raw sequencing reads and successfully differentiated multiple co-infecting strains present in a sample. In addition, PRRSV strain information was obtained from clinical samples containing 10(4) to 10(6) viral copies or more within 6 hours of sequencing. Overall, direct viral RNA sequencing followed by bioinformatic analysis proves to be a promising approach for identification of the viral strain or strains involved in clinical infections, allowing for more precise prevention and control strategies during PRRSV outbreaks.",2019 Dec 7,"['Tan, Shaoyuan', 'Dvorak, Cheryl M.T.', 'Murtaugh, Michael P.']",Viruses,,,True
e576c57618f99c0f5073d66ebedee4d80e910e0c,PMC,"Distinct Lineages of Feline Parvovirus Associated with Epizootic Outbreaks in Australia, New Zealand and the United Arab Emirates",http://dx.doi.org/10.3390/v11121155,PMC6950618,31847268,CC BY,"Feline panleukopenia (FPL), a frequently fatal disease of cats, is caused by feline parvovirus (FPV) or canine parvovirus (CPV). We investigated simultaneous outbreaks of FPL between 2014 and 2018 in Australia, New Zealand and the United Arab Emirates (UAE) where FPL outbreaks had not been reported for several decades. Case data from 989 cats and clinical samples from additional 113 cats were obtained to determine the cause of the outbreaks and epidemiological factors involved. Most cats with FPL were shelter-housed, 9 to 10 weeks old at diagnosis, unvaccinated, had not completed a primary vaccination series or had received vaccinations noncompliant with current guidelines. Analysis of parvoviral VP2 sequence data confirmed that all FPL cases were caused by FPV and not CPV. Phylogenetic analysis revealed that each of these outbreaks was caused by a distinct FPV, with two virus lineages present in eastern Australia and virus movement between different geographical locations. Viruses from the UAE outbreak formed a lineage of unknown origin. FPV vaccine virus was detected in the New Zealand cases, highlighting the difficulty of distinguishing the co-incidental shedding of vaccine virus in vaccinated cats. Inadequate vaccination coverage in shelter-housed cats was a common factor in all outbreaks, likely precipitating the multiple re-emergence of infection events.",2019 Dec 13,"['Van Brussel, Kate', 'Carrai, Maura', 'Lin, Carrie', 'Kelman, Mark', 'Setyo, Laura', 'Aberdein, Danielle', 'Brailey, Juliana', 'Lawler, Michelle', 'Maher, Simone', 'Plaganyi, Ildiko', 'Lewis, Emily', 'Hawkswell, Adele', 'Allison, Andrew B.', 'Meers, Joanne', 'Martella, Vito', 'Beatty, Julia A.', 'Holmes, Edward C.', 'Decaro, Nicola', 'Barrs, Vanessa R.']",Viruses,,,True
2b46b2e0798f4e27871c942a86515bdcc64a4a44,PMC,Genome editing for disease resistance in pigs and chickens,http://dx.doi.org/10.1093/af/vfz013,PMC6951997,32002257,CC BY,,2019 Jun 25,"['Proudfoot, Chris', 'Lillico, Simon', 'Tait-Burkard, Christine']",Anim Front,,,True
19ebb3ea64083a71dcf7b9c2cd53bc49ec1a90ca,PMC,Infectious disease pandemic planning and response: Incorporating decision analysis,http://dx.doi.org/10.1371/journal.pmed.1003018,PMC6952100,31917786,CC BY,Freya Shearer and co-authors discuss the use of decision analysis in planning for infectious disease pandemics.,2020 Jan 9,"['Shearer, Freya M.', 'Moss, Robert', 'McVernon, Jodie', 'Ross, Joshua V.', 'McCaw, James M.']",PLoS Med,,,True
397fe94fcd6118c9d0b40283a806525300c16156,PMC,Infectious disease pandemic planning and response: Incorporating decision analysis,http://dx.doi.org/10.1371/journal.pmed.1003018,PMC6952100,31917786,CC BY,Freya Shearer and co-authors discuss the use of decision analysis in planning for infectious disease pandemics.,2020 Jan 9,"['Shearer, Freya M.', 'Moss, Robert', 'McVernon, Jodie', 'Ross, Joshua V.', 'McCaw, James M.']",PLoS Med,,,True
f0c4d40e1879dd1a049298f151940ac168b5f5a7,PMC,"Nearly Complete Genome Sequence of an Echovirus 30 Strain from a Cluster of Aseptic Meningitis Cases in California, September 2017",http://dx.doi.org/10.1128/MRA.01085-19,PMC6953510,31672747,CC BY,"We report the nearly complete genome sequence of a human enterovirus, a strain of echovirus 30, obtained from a cerebrospinal fluid specimen from a teenaged patient with aseptic meningitis in September 2017.",2019 Oct 31,"['Pan, Chao-Yang', 'Huynh, Thalia', 'Padilla, Tasha', 'Chen, Alice', 'Ng, Terry Fei Fan', 'Marine, Rachel L.', 'Castro, Christina J.', 'Nix, W. Allan', 'Wadford, Debra A.']",Microbiol Resour Announc,,,True
7c4bdc3231574dc0086b9ebfd3729823a92cc63b,PMC,"Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV",http://dx.doi.org/10.1038/s41467-019-13940-6,PMC6954302,31924756,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.",2020 Jan 10,"['Sheahan, Timothy P.', 'Sims, Amy C.', 'Leist, Sarah R.', 'Schäfer, Alexandra', 'Won, John', 'Brown, Ariane J.', 'Montgomery, Stephanie A.', 'Hogg, Alison', 'Babusis, Darius', 'Clarke, Michael O.', 'Spahn, Jamie E.', 'Bauer, Laura', 'Sellers, Scott', 'Porter, Danielle', 'Feng, Joy Y.', 'Cihlar, Tomas', 'Jordan, Robert', 'Denison, Mark R.', 'Baric, Ralph S.']",Nat Commun,,,False
ba8e90adc7a5db77455efde430950daf16d3217f,PMC,"Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV",http://dx.doi.org/10.1038/s41467-019-13940-6,PMC6954302,31924756,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.",2020 Jan 10,"['Sheahan, Timothy P.', 'Sims, Amy C.', 'Leist, Sarah R.', 'Schäfer, Alexandra', 'Won, John', 'Brown, Ariane J.', 'Montgomery, Stephanie A.', 'Hogg, Alison', 'Babusis, Darius', 'Clarke, Michael O.', 'Spahn, Jamie E.', 'Bauer, Laura', 'Sellers, Scott', 'Porter, Danielle', 'Feng, Joy Y.', 'Cihlar, Tomas', 'Jordan, Robert', 'Denison, Mark R.', 'Baric, Ralph S.']",Nat Commun,,,False
ba54bfe08b8b1209af6aed6ade15876106f0dabd,PMC,"Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV",http://dx.doi.org/10.1038/s41467-019-13940-6,PMC6954302,31924756,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.",2020 Jan 10,"['Sheahan, Timothy P.', 'Sims, Amy C.', 'Leist, Sarah R.', 'Schäfer, Alexandra', 'Won, John', 'Brown, Ariane J.', 'Montgomery, Stephanie A.', 'Hogg, Alison', 'Babusis, Darius', 'Clarke, Michael O.', 'Spahn, Jamie E.', 'Bauer, Laura', 'Sellers, Scott', 'Porter, Danielle', 'Feng, Joy Y.', 'Cihlar, Tomas', 'Jordan, Robert', 'Denison, Mark R.', 'Baric, Ralph S.']",Nat Commun,,,False
6c3e8d0fde7d37c97f68675d4d8012c9445be551,PMC,"Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV",http://dx.doi.org/10.1038/s41467-019-13940-6,PMC6954302,31924756,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.",2020 Jan 10,"['Sheahan, Timothy P.', 'Sims, Amy C.', 'Leist, Sarah R.', 'Schäfer, Alexandra', 'Won, John', 'Brown, Ariane J.', 'Montgomery, Stephanie A.', 'Hogg, Alison', 'Babusis, Darius', 'Clarke, Michael O.', 'Spahn, Jamie E.', 'Bauer, Laura', 'Sellers, Scott', 'Porter, Danielle', 'Feng, Joy Y.', 'Cihlar, Tomas', 'Jordan, Robert', 'Denison, Mark R.', 'Baric, Ralph S.']",Nat Commun,,,True
b9642bbf29d039de465c0b9cd7ab98ba0b81cd09,PMC,Infectious Diseases among Refugee Children,http://dx.doi.org/10.3390/children6120129,PMC6955676,31783605,CC BY,"In recent years, there has been a substantial increase in refugee and asylum-seeking adults, adolescents and children to high-income countries. Infectious diseases remain the most frequently identified medical diagnosis among U.S.-bound refugee children. Medical screening and immunization are key strategies to reduce the risk of infectious diseases in refugee, internationally adopted, and immigrant children. Notable infectious diseases affecting refugee and other newly arriving migrants include latent or active tuberculosis, human immunodeficiency virus type 1 (HIV), hepatitis B, hepatitis C, vaccine-preventable diseases, malaria, and other parasitic infections. The U.S. Centers for Disease Control and Prevention and the American Academy of Pediatrics have published guidelines for health assessment of newly arriving immigrant, refugee, and internationally adopted children. Although, data on the health risks and needs of refugee exists in some high-income countries, there is an urgent need to develop robust evidence-informed guidance on screening for infectious diseases and vaccination strategies on a broader scale to inform national policies. Innovative approaches to reach migrant communities in the host nations, address health and other complex barriers to improve access to high-quality integrated health services, and strong advocacy to mobilize resources to improve health, safety, and wellbeing for refugee children and their families are urgent priorities.",2019 Nov 27,"Shetty, Avinash K.",Children (Basel),,,True
8e89329ba5682ffd98598d5b5c6ccd2067abdd12,PMC,Advances in Directly Amplifying Nucleic Acids from Complex Samples,http://dx.doi.org/10.3390/bios9040117,PMC6955841,31574959,CC BY,"Advances in nucleic acid amplification technologies have revolutionized diagnostics for systemic, inherited, and infectious diseases. Current assays and platforms, however, often require lengthy experimental procedures and multiple instruments to remove contaminants and inhibitors from clinically-relevant, complex samples. This requirement of sample preparation has been a bottleneck for using nucleic acid amplification tests (NAATs) at the point of care (POC), though advances in “lab-on-chip” platforms that integrate sample preparation and NAATs have made great strides in this space. Alternatively, direct NAATs—techniques that minimize or even bypass sample preparation—present promising strategies for developing POC diagnostic tools for analyzing real-world samples. In this review, we discuss the current status of direct NAATs. Specifically, we surveyed potential testing systems published from 1989 to 2017, and analyzed their performances in terms of robustness, sensitivity, clinical relevance, and suitability for POC diagnostics. We introduce bubble plots to facilitate our analysis, as bubble plots enable effective visualization of the performances of these direct NAATs. Through our review, we hope to initiate an in-depth examination of direct NAATs and their potential for realizing POC diagnostics, and ultimately transformative technologies that can further enhance healthcare.",2019 Sep 30,"['Walker, Faye M.', 'Hsieh, Kuangwen']",Biosensors (Basel),,,True
604491e627b3cb8661ee7f8747623eb4c61f0315,PMC,A Case History in Cooperative Biological Research: Compendium of Studies and Program Analyses in Kazakhstan,http://dx.doi.org/10.3390/tropicalmed4040136,PMC6958332,31717575,CC BY,"Kazakhstan and the United States have partnered since 2003 to counter the proliferation of weapons of mass destruction. The US Department of Defense (US DoD) has funded threat reduction programs to eliminate biological weapons, secure material in repositories that could be targeted for theft, and enhance surveillance systems to monitor infectious disease outbreaks that would affect national security. The cooperative biological research (CBR) program of the US DoD’s Biological Threat Reduction Program has provided financing, mentorship, infrastructure, and biologic research support to Kazakhstani scientists and research institutes since 2005. The objective of this paper is to provide a historical perspective for the CBR involvement in Kazakhstan, including project chronology, successes and challenges to allow lessons learned to be applied to future CBR endeavors. A project compendium from open source data and interviews with partner country Kazakhstani participants, project collaborators, and stakeholders was developed utilizing studies from 2004 to the present. An earlier project map was used as a basis to determine project linkages and continuations during the evolution of the CBR program. It was determined that consistent and effective networking increases the chances to collaborate especially for competitive funding opportunities. Overall, the CBR program has increased scientific capabilities in Kazakhstan while reducing their risk of biological threats. However, there is still need for increased scientific transparency and an overall strategy to develop a capability-based model to better enhance and sustain future research. Finally, we offer a living perspective that can be applied to further link related studies especially those related to One Health and zoonoses and the assessment of similar capability-building programs.",2019 Nov 9,"['Yeh, Kenneth B.', 'Parekh, Falgunee K.', 'Musralina, Lyazzat', 'Sansyzbai, Ablay', 'Tabynov, Kairat', 'Shapieva, Zhanna', 'Richards, Allen L.', 'Hay, John']",Trop Med Infect Dis,,,True
7e5ab55e74c377b2a3bd936030ffe0f92d4c2a78,PMC,Candida auris: A Review of Recommendations for Detection and Control in Healthcare Settings,http://dx.doi.org/10.3390/jof5040111,PMC6958335,31795175,CC BY,"Candida auris is an emerging multidrug-resistant fungal pathogen. Since first reported in 2009, C. auris has caused healthcare outbreaks around the world, often involving high mortality. Identification of C. auris has been a major challenge as many common conventional laboratory methods cannot accurately detect it. Early detection and implementation of infection control practices can prevent its spread. The aim of this review is to describe recommendations for the detection and control of C. auris in healthcare settings.",2019 Nov 28,"['Caceres, Diego H.', 'Forsberg, Kaitlin', 'Welsh, Rory M.', 'Sexton, David Joseph', 'Lockhart, Shawn R.', 'Jackson, Brendan R.', 'Chiller, Tom']",J Fungi (Basel),,,True
ac433e9c802d7f78f6b05a4ac8aedf3aee005086,PMC,Ongoing Challenges with Healthcare-Associated Candida auris Outbreaks in Oman,http://dx.doi.org/10.3390/jof5040101,PMC6958405,31652825,CC BY,"Candida auris has emerged in the past decade as a multi-drug resistant public health threat causing health care outbreaks. Here we report epidemiological, clinical, and microbiological investigations of a C. auris outbreak in a regional Omani hospital between April 2018 and April 2019. The outbreak started in the intensive care areas (intensive care unit (ICU), coronary care unit (CCU), and high dependency unit) but cases were subsequently diagnosed in other medical and surgical units. In addition to the patients’ clinical and screening samples, environmental swabs from high touch areas and from the hands of 35 staff were collected. All the positive samples from patients and environmental screening were confirmed using MALDI-TOF, and additional ITS-rDNA sequencing was done for ten clinical and two environmental isolates. There were 32 patients positive for C. auris of which 14 (43.8%) had urinary tract infection, 11 (34.4%) had candidemia, and 7 (21.8%) had asymptomatic skin colonization. The median age was 64 years (14–88) with 17 (53.1%) male and 15 (46.9%) female patients. Prior to diagnosis, 21 (65.6%) had been admitted to the intensive care unit, and 11 (34.4%) had been nursed in medical or surgical wards. The crude mortality rate in our patient’s cohort was 53.1. Two swabs collected from a ventilator in two different beds in the ICU were positive for C. auris. None of the health care worker samples were positive. Molecular typing showed that clinical and environmental isolates were genetically similar and all belonged to the South Asian C. auris clade I. Most isolates had non-susceptible fluconazole (100%) and amphotericin B (33%) minimal inhibitory concentrations (MICs), but had low echinocandin and voriconazole MICs. Despite multimodal infection prevention and control measures, new cases continued to appear, challenging all the containment efforts.",2019 Oct 23,"['Al Maani, Amal', 'Paul, Hema', 'Al-Rashdi, Azza', 'Al Wahaibi, Adil', 'Al-Jardani, Amina', 'Al Abri, Asma M. Ali', 'AlBalushi, Mariam A. H.', 'Al Abri, Seif', 'Al Reesi, Mohammed', 'Al Maqbali, Ali', 'Al Kasaby, Nashwa M.', 'de Groot, Theun', 'F. Meis, Jacques', 'Al-Hatmi, Abdullah M. S.']",J Fungi (Basel),,,True
871bc5983e4188a32f9cfda1adb07fdbf760f891,PMC,"Alternative Experimental Models for Studying Influenza Proteins, Host–Virus Interactions and Anti-Influenza Drugs",http://dx.doi.org/10.3390/ph12040147,PMC6958409,31575020,CC BY,"Ninety years after the discovery of the virus causing the influenza disease, this malady remains one of the biggest public health threats to mankind. Currently available drugs and vaccines only partially reduce deaths and hospitalizations. Some of the reasons for this disturbing situation stem from the sophistication of the viral machinery, but another reason is the lack of a complete understanding of the molecular and physiological basis of viral infections and host–pathogen interactions. Even the functions of the influenza proteins, their mechanisms of action and interaction with host proteins have not been fully revealed. These questions have traditionally been studied in mammalian animal models, mainly ferrets and mice (as well as pigs and non-human primates) and in cell lines. Although obviously relevant as models to humans, these experimental systems are very complex and are not conveniently accessible to various genetic, molecular and biochemical approaches. The fact that influenza remains an unsolved problem, in combination with the limitations of the conventional experimental models, motivated increasing attempts to use the power of other models, such as low eukaryotes, including invertebrate, and primary cell cultures. In this review, we summarized the efforts to study influenza in yeast, Drosophila, zebrafish and primary human tissue cultures and the major contributions these studies have made toward a better understanding of the disease. We feel that these models are still under-utilized and we highlight the unique potential each model has for better comprehending virus–host interactions and viral protein function.",2019 Sep 30,"['Chua, Sonja C. J. H.', 'Tan, Hui Qing', 'Engelberg, David', 'Lim, Lina H. K.']",Pharmaceuticals (Basel),,,True
efad73082938e5a567397ede3fc326988ea72bb8,PMC,"Influence of Colostrum and Vitamins A, D(3), and E on Early Intestinal Colonization of Neonatal Holstein Calves Infected with Mycobacterium avium subsp. paratuberculosis",http://dx.doi.org/10.3390/vetsci6040093,PMC6958420,31756892,CC BY,"Exposure of neonates to Mycobacterium avium subsp. paratuberculosis (MAP) via infected dams is the primary mode of transmission of Johne’s disease. Little is known about the impacts of feeding colostrum and supplemental vitamins on the gut microbiome in calves exposed to MAP. In the present study, calves were assigned at birth to one of six treatment groups: (1) Colostrum deprived (CD), no vitamins; (2) colostrum replacer (CR), no vitamins; (3) CR, vitamin A; (4) CR, vitamin D(3); (5) CR, vitamin E; (6) CR, vitamins A, D(3), E, with five calves per treatment in a 14-day study. All calves were orally inoculated with MAP on days 1 and 3 of the study. Differences due to vitamin supplementation were not significant but treatment groups CR-A, CR-E, and CR-ADE had higher numbers of MAP-positive tissues overall. Shannon diversity indices demonstrated regional differences in microbial communities, primarily Proteobacteria, Bacteroidetes, and Firmicutes, between the ileum, cecum, and spiral colon of all calves. CD calves exhibited increased richness compared with CR calves in the cecum and spiral colon and harbored increased Proteobacteria and decreased Bacteroidetes in the mucosa compared with the lumen for all three tissues. Overall, supplementation with vitamins did not appear to influence gut microbiome or impact MAP infection. Feeding of colostrum influenced gut microbiome and resulted in fewer incidences of dysbiosis.",2019 Nov 20,"['Stabel, Judith', 'Krueger, Lucas', 'Jenvey, Caitlin', 'Wherry, Taylor', 'Hostetter, Jesse', 'Beitz, Donald']",Vet Sci,,,True
cbe57a2150ad229d69d2ea7154d9245620c846c3,PMC,Future Pandemic Influenza Virus Detection Relies on the Existing Influenza Surveillance Systems: A Perspective from Australia and New Zealand,http://dx.doi.org/10.3390/tropicalmed4040121,PMC6958477,31547606,CC BY,"The anniversary of the 1918–1919 influenza pandemic has allowed a refocusing on the global burden of influenza and the importance of co-ordinated international surveillance for both seasonal influenza and the identification of control strategies for future pandemics. Since the introduction of the International Health Regulations (IHR), progress had been slow, until the emergence of the novel influenza A(H1N1)2009 virus and its global spread, which has led to the World Health Organization (WHO) developing a series of guidance documents on global influenza surveillance procedures, severity and risk assessments, and essential measurements for the determination of national pandemic responses. However, the greatest burden of disease from influenza occurs between pandemics during seasonal influenza outbreaks and epidemics. Both Australia and New Zealand utilise seasonal influenza surveillance to support national influenza awareness programs focused on seasonal influenza vaccination education and promotion. These programs also serve to promote the importance of pandemic preparedness.",2019 Sep 23,"['Jennings, Lance C.', 'Barr, Ian G.']",Trop Med Infect Dis,,,True
2c7260dadc28671d3ba4e14120b63a5232765805,PMC,"Meningococcal Vaccine for Hajj Pilgrims: Compliance, Predictors, and Barriers",http://dx.doi.org/10.3390/tropicalmed4040127,PMC6958484,31618945,CC BY,"Background: Major intercontinental outbreaks of invasive meningococcal disease associated with the Hajj occurred in 1987, 2000, and 2001. Mandatory meningococcal vaccination for all pilgrims against serogroups A and C and, subsequently, A, C, W, and Y controlled the epidemics. Overseas pilgrims show excellent adherence to the policy; however, vaccine uptake among domestic pilgrims is suboptimal. This survey aimed to evaluate meningococcal vaccine uptake among Hajj pilgrims and to identify key factors affecting this. Methods: An anonymous cross-sectional survey was conducted among pilgrims in Greater Makkah during the Hajj in 2017–2018. Data on socio-demographic characteristics, vaccination status, cost of vaccination, and reasons behind non-receipt of the vaccine were collected. Results: A total of 509 respondents aged 13 to 82 (median 33.8) years participated in the survey: 86% male, 85% domestic pilgrims. Only 389/476 (81.7%) confirmed their meningococcal vaccination status; 64 individuals (13.4%), all domestic pilgrims, did not receive the vaccine, and 23 (4.8%) were unsure. Among overseas pilgrims, 93.5% certainly received the vaccine (6.5% were unsure) compared to 80.9% of domestic pilgrims (p < 0.01). Being employed and having a tertiary qualification were significant predictors of vaccination adherence (odds ratio (OR) = 2.2, 95% confidence interval (CI) = 1.3–3.8, p < 0.01; and OR = 1.7, CI = 1–2.5, p < 0.05, respectively). Those who obtained pre-Hajj health advice were more than three times as likely to be vaccinated than those who did not (OR = 3.3, CI = 1.9–5.9, p < 0.001). Lack of awareness (63.2%, 36/57) and lack of time (15.8%, 9/57) were the most common reasons reported for non-receipt of vaccine. Conclusion: Many domestic pilgrims missed the compulsory meningococcal vaccine; in this regard, lack of awareness is a key barrier. Being an overseas pilgrim (or living at a distance from Makkah), receipt of pre-Hajj health advice, and employment were predictors of greater compliance with the vaccination policy. Opportunities remain to reduce the policy–practice gap among domestic pilgrims.",2019 Oct 15,"['Badahdah, Al-Mamoon', 'Alghabban, Fatimah', 'Falemban, Wajd', 'Albishri, Abdullah', 'Rani Banik, Gouri', 'Alhawassi, Tariq', 'Abuelizz, Hatem', 'Bakarman, Marwan A.', 'Khatami, Ameneh', 'Booy, Robert', 'Rashid, Harunor']",Trop Med Infect Dis,,,True
9998f6aa94bb384f3a93381c404f85506d2a8f7d,PMC,"An evaluation of the Zambia influenza sentinel surveillance system, 2011–2017",http://dx.doi.org/10.1186/s12913-019-4884-5,PMC6958603,31931793,CC BY,"BACKGROUND: Over the past decade, influenza surveillance has been established in several African countries including Zambia. However, information on the on data quality and reliability of established influenza surveillance systems in Africa are limited. Such information would enable countries to assess the performance of their surveillance systems, identify shortfalls for improvement and provide evidence of data reliability for policy making and public health interventions. METHODS: We used the Centers for Disease Control and Prevention guidelines to evaluate the performance of the influenza surveillance system (ISS) in Zambia during 2011–2017 using 9 attributes: (i) data quality and completeness, (ii) timeliness, (iii) representativeness, (iv) flexibility, (v) simplicity, (vi) acceptability, (vii) stability, (viii) utility, and (ix) sustainability. Each attribute was evaluated using pre-defined indicators. For each indicator we obtained the proportion (expressed as percentage) of the outcome of interest over the total. A scale from 1 to 3 was used to provide a score for each attribute as follows: < 60% (as obtained in the calculation above) scored 1 (weak performance); 60–79% scored 2 (moderate performance); ≥80% scored 3 (good performance). An overall score for each attribute and the ISS was obtained by averaging the scores of all evaluated attributes. RESULTS: The overall mean score for the ISS in Zambia was 2.6. Key strengths of the system were the quality of data generated (score: 2.9), its flexibility (score: 3.0) especially to monitor viral pathogens other than influenza viruses, its simplicity (score: 2.8), acceptability (score: 3.0) and stability (score: 2.6) over the review period and its relatively low cost ($310,000 per annum). Identified weaknesses related mainly to geographic representativeness (score: 2.0), timeliness (score: 2.5), especially in shipment of samples from remote sites, and sustainability (score: 1.0) in the absence of external funds. CONCLUSIONS: The system performed moderately well in our evaluation. Key improvements would include improvements in the timeliness of samples shipments and geographical coverage. However, these improvements would result in increased cost and logistical complexity. The ISSS in Zambia is largely reliant on external funds and the acceptability of maintaining the surveillance system through national funds would require evaluation.",2020 Jan 13,"['Simusika, Paul', 'Tempia, Stefano', 'Chentulo, Edward', 'Polansky, Lauren', 'Mazaba, Mazyanga Lucy', 'Ndumba, Idah', 'Mbewe, Quinn K.', 'Monze, Mwaka']",BMC Health Serv Res,,,True
78b06344bf1d834407a41bceb4999839085b0082,PMC,Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I),http://dx.doi.org/10.3389/fimmu.2019.02995,PMC6960135,31969884,CC BY,"To investigate CTL epitope applications in swine, SLA-1(*)1502-restricted peptide epitopes matching porcine reproductive and respiratory syndrome virus (PRRSV) strains were explored by crystallography, biochemistry, and the specific pathogen-free (SPF) swine experiments. First, nine predicted PRRSV peptides were tested by assembly of the peptide-SLA-1(*)1502 (pSLA-1(*)1502) complexes, and the crystal structure of the SLA-1(*)1502 complex with one peptide (NSP9-TMP9) was determined. The NSP9-TMP9 peptide conformation presented by pSLA-1(*)1502 is different from that of the peptides presented by the known pSLA-1(*)0401 and pSLA-3(*)hs0202 complexes. Two consecutive Pro residues make the turn between P3 and P4 of NSP9-TMP9 much sharper. The D pocket of pSLA-1(*)1502 is unique and is important for peptide binding. Next, the potential SLA-1(*)1502-restricted peptide epitopes matching four typical genetic PRRSV strains were identified based on the peptide-binding motif of SLA-1(*)1502 determined by structural analysis and alanine scanning of the NSP9-TMP9 peptide. The tetrameric complex of SLA-1(*)1502 and NSP9-TMP9 was constructed and examined. Finally, taking NSP9-TMP9 as an example, the CTL immunogenicity of the identified PRRSV peptide epitope was evaluated. The SPF swine expressing the SLA-1(*)1502 alleles were divided into three groups: modified live vaccine (MLV), MLV+NSP9-TMP9, and the blank control group. NSP9-TMP9 was determined as a PRRSV CTL epitope with strong immunogenicity by flow cytometry and IFN-γ expression. Our study developed an integrated approach to identify SLA-I-restricted CTL epitopes from various important viruses and is helpful in designing and applying effective peptide-based vaccines for swine.",2020 Jan 8,"['Pan, Xiaocheng', 'Zhang, Nianzhi', 'Wei, Xiaohui', 'Jiang, Yinan', 'Chen, Rong', 'Li, Qirun', 'Liang, Ruiying', 'Zhang, Lijie', 'Ma, Lizhen', 'Xia, Chun']",Front Immunol,,,True
e24e562b0fc39ee100724833115384f3c56ffd6d,PMC,Note from the editors: Don’t stop thinking about tomorrow,http://dx.doi.org/10.2807/1560-7917.ES.2020.25.1.2001091,PMC6961261,31937393,CC BY,,2020 Jan 9,,Euro Surveill,,,True
54775274bbf4947d5312a62a87bedfb1264d7f87,PMC,"The impact of repeated vaccination using 10-year vaccination history on protection against influenza in older adults: a test-negative design study across the 2010/11 to 2015/16 influenza seasons in Ontario, Canada",http://dx.doi.org/10.2807/1560-7917.ES.2020.25.1.1900245,PMC6961264,31937397,CC BY,"INTRODUCTION: Annual influenza vaccination is recommended for older adults, but evidence regarding the impact of repeated vaccination has been inconclusive. AIM: We investigated vaccine effectiveness (VE) against laboratory-confirmed influenza and the impact of repeated vaccination over 10 previous seasons on current season VE among older adults. METHODS: We conducted an observational test-negative study in community-dwelling adults aged > 65 years in Ontario, Canada for the 2010/11 to 2015/16 seasons by linking laboratory and health administrative data. We estimated VE using multivariable logistic regression. We assessed the impact of repeated vaccination by stratifying by previous vaccination history. RESULTS: We included 58,304 testing episodes for respiratory viruses, with 11,496 (20%) testing positive for influenza and 31,004 (53%) vaccinated. Adjusted VE against laboratory-confirmed influenza for the six seasons combined was 21% (95% confidence interval (CI): 18 to 24%). Patients who were vaccinated in the current season, but had received no vaccinations in the previous 10 seasons, had higher current season VE (34%; 95%CI: 9 to 52%) than patients who had received 1–3 (26%; 95%CI: 13 to 37%), 4–6 (24%; 95%CI: 15 to 33%), 7–8 (13%; 95%CI: 2 to 22%), or 9–10 (7%; 95%CI: −4 to 16%) vaccinations (trend test p = 0.001). All estimates were higher after correcting for misclassification of current season vaccination status. For patients who were not vaccinated in the current season, residual protection rose significantly with increasing numbers of vaccinations received previously. CONCLUSIONS: Although VE appeared to decrease with increasing numbers of previous vaccinations, current season vaccination likely provides some protection against influenza regardless of the number of vaccinations received over the previous 10 influenza seasons.",2020 Jan 9,"['Kwong, Jeffrey C', 'Chung, Hannah', 'Jung, James KH', 'Buchan, Sarah A', 'Campigotto, Aaron', 'Campitelli, Michael A', 'Crowcroft, Natasha S', 'Gubbay, Jonathan B', 'Karnauchow, Timothy', 'Katz, Kevin', 'McGeer, Allison J', 'McNally, J Dayre', 'Richardson, David C', 'Richardson, Susan E', 'Rosella, Laura C', 'Schwartz, Kevin L', 'Simor, Andrew', 'Smieja, Marek', 'Zahariadis, George', None]",Euro Surveill,,,False
20317b47f1178792d735b4202fc343721d1ff4a5,PMC,"The impact of repeated vaccination using 10-year vaccination history on protection against influenza in older adults: a test-negative design study across the 2010/11 to 2015/16 influenza seasons in Ontario, Canada",http://dx.doi.org/10.2807/1560-7917.ES.2020.25.1.1900245,PMC6961264,31937397,CC BY,"INTRODUCTION: Annual influenza vaccination is recommended for older adults, but evidence regarding the impact of repeated vaccination has been inconclusive. AIM: We investigated vaccine effectiveness (VE) against laboratory-confirmed influenza and the impact of repeated vaccination over 10 previous seasons on current season VE among older adults. METHODS: We conducted an observational test-negative study in community-dwelling adults aged > 65 years in Ontario, Canada for the 2010/11 to 2015/16 seasons by linking laboratory and health administrative data. We estimated VE using multivariable logistic regression. We assessed the impact of repeated vaccination by stratifying by previous vaccination history. RESULTS: We included 58,304 testing episodes for respiratory viruses, with 11,496 (20%) testing positive for influenza and 31,004 (53%) vaccinated. Adjusted VE against laboratory-confirmed influenza for the six seasons combined was 21% (95% confidence interval (CI): 18 to 24%). Patients who were vaccinated in the current season, but had received no vaccinations in the previous 10 seasons, had higher current season VE (34%; 95%CI: 9 to 52%) than patients who had received 1–3 (26%; 95%CI: 13 to 37%), 4–6 (24%; 95%CI: 15 to 33%), 7–8 (13%; 95%CI: 2 to 22%), or 9–10 (7%; 95%CI: −4 to 16%) vaccinations (trend test p = 0.001). All estimates were higher after correcting for misclassification of current season vaccination status. For patients who were not vaccinated in the current season, residual protection rose significantly with increasing numbers of vaccinations received previously. CONCLUSIONS: Although VE appeared to decrease with increasing numbers of previous vaccinations, current season vaccination likely provides some protection against influenza regardless of the number of vaccinations received over the previous 10 influenza seasons.",2020 Jan 9,"['Kwong, Jeffrey C', 'Chung, Hannah', 'Jung, James KH', 'Buchan, Sarah A', 'Campigotto, Aaron', 'Campitelli, Michael A', 'Crowcroft, Natasha S', 'Gubbay, Jonathan B', 'Karnauchow, Timothy', 'Katz, Kevin', 'McGeer, Allison J', 'McNally, J Dayre', 'Richardson, David C', 'Richardson, Susan E', 'Rosella, Laura C', 'Schwartz, Kevin L', 'Simor, Andrew', 'Smieja, Marek', 'Zahariadis, George', None]",Euro Surveill,,,True
0d83a837839b75104b3925a1a0be27ea2883b419,PMC,Estimating epidemic exponential growth rate and basic reproduction number,http://dx.doi.org/10.1016/j.idm.2019.12.009,PMC6962332,31956741,CC BY,"The initial exponential growth rate of an epidemic is an important measure of the severeness of the epidemic, and is also closely related to the basic reproduction number. Estimating the growth rate from the epidemic curve can be a challenge, because of its decays with time. For fast epidemics, the estimation is subject to over-fitting due to the limited number of data points available, which also limits our choice of models for the epidemic curve. We discuss the estimation of the growth rate using maximum likelihood method and simple models.",2020 Jan 8,"Ma, Junling",Infect Dis Model,,,False
8857ba8944f2ae93f5af2424992a8cfcac85765a,PMC,Infection Prevention Measures for Surgical Procedures during a Middle East Respiratory Syndrome Outbreak in a Tertiary Care Hospital in South Korea,http://dx.doi.org/10.1038/s41598-019-57216-x,PMC6962363,31941957,CC BY,"In 2015, we experienced the largest in-hospital Middle East respiratory syndrome (MERS) outbreak outside the Arabian Peninsula. We share the infection prevention measures for surgical procedures during the unexpected outbreak at our hospital. We reviewed all forms of related documents and collected information through interviews with healthcare workers of our hospital. After the onset of outbreak, a multidisciplinary team devised institutional MERS-control guidelines. Two standard operating rooms were converted to temporary negative-pressure rooms by physically decreasing the inflow air volume (−4.7 Pa in the main room and −1.2 Pa in the anteroom). Healthcare workers were equipped with standard or enhanced personal protective equipment according to the MERS-related patient’s profile and symptoms. Six MERS-related patients underwent emergency surgery, including four MERS-exposed and two MERS-confirmed patients. Negative conversion of MERS-CoV polymerase chain reaction tests was noticed for MERS-confirmed patients before surgery. MERS-exposed patients were also tested twice preoperatively, all of which were negative. All operative procedures in MERS-related patients were performed without specific adverse events or perioperative MERS transmission. Our experience with setting up a temporary negative-pressure operation room and our conservative approach for managing MERS-related patients can be referred in cases of future unexpected MERS outbreaks in non-endemic countries.",2020 Jan 15,"['Park, Jiyeon', 'Yoo, Seung Yeon', 'Ko, Jae-Hoon', 'Lee, Sangmin M.', 'Chung, Yoon Joo', 'Lee, Jong-Hwan', 'Peck, Kyong Ran', 'Min, Jeong Jin']",Sci Rep,,,True
111e82fd55d8b42cd523cf365b53dfcdaa2165d3,PMC,A Recombinant La Sota Vaccine Strain Expressing Multiple Epitopes of Infectious Bronchitis Virus (IBV) Protects Specific Pathogen-Free (SPF) Chickens against IBV and NDV Challenges,http://dx.doi.org/10.3390/vaccines7040170,PMC6963182,31683905,CC BY,"Infectious bronchitis (IB) and Newcastle disease (ND) are two major infectious diseases that are a threat to the domestic poultry industry. In this study, we successfully generated a recombinant LaSota candidate vaccine strain, rNDV-IBV-T/B, which expresses a short, synthetic, previously identified IBV S1 multi-epitope cassette using the reverse genetic system. The recombinant virus was propagated in nine-day-old embryonated chicken eggs for 20 passages and genetic stability was confirmed by whole genome DNA sequencing. The recombinant virus had a hemagglutination (HA) titer of 2(10), mean death time (MDT) of 118 hours, and intracerebral pathogenicity index (ICPI) of 0.05. None of these were significantly different from the parental Newcastle disease virus (NDV) LaSota strain (p > 0.05). Vaccination of white leghorn chickens at one day of age with 10(6) EID(50) rNDV-IBV-T/B provided 90% protection against virulent IBV M41 challenge at three weeks of age, which was significantly higher than the protection of the control group vaccinated with phosphate-buffered saline (PBS) (p < 0.05). The ciliostasis scores of rNDV-IBV-T/B-vaccinated and LaSota-vaccinated groups were 4.2 and 37.6, respectively, which indicated that rNDV-IBV-T/B vaccination reduced the pathogenicity of IBV toward the trachea. Furthermore, real-time RT-PCR assay showed that the rNDV-IBV-T/B vaccination resulted in low levels of viral load (647.80 ± 49.65 RNA copies) in the trachea four days post-challenge, which is significantly lower than groups vaccinated with PBS (8591.25 ± 311.10 RNA copies) or LaSota (7742.60 ± 298.50 RNA copies) (p < 0.05). Meanwhile, the same dose of rNDV-IBV-T/B vaccination provided complete protection against velogenic NDV F48E9 challenge. These results demonstrate that the rNDV-IBV-T/B strain is a promising vaccine candidate to control both IB and ND simultaneously. Furthermore, epitope-based live vector vaccines provide an alternative strategy for the development of cost-effective and, broadly, cross-protective vaccines.",2019 Nov 1,"['Tan, Lei', 'Wen, Guoyuan', 'Qiu, Xusheng', 'Yuan, Yanmei', 'Meng, Chunchun', 'Sun, Yingjie', 'Liao, Ying', 'Song, Cuiping', 'Liu, Weiwei', 'Shi, Yonghong', 'Shao, Huabin', 'Ding, Chan']",Vaccines (Basel),,,True
22450e467873a3cf4f2627d36d6f71aa779520c4,PMC,Post-Glycosylation Modification of Sialic Acid and Its Role in Virus Pathogenesis,http://dx.doi.org/10.3390/vaccines7040171,PMC6963189,31683930,CC BY,"Sialic acids are a family of nine carbon keto-aldononulosonic acids presented at the terminal ends of glycans on cellular membranes. α-Linked sialoglycoconjugates often undergo post-glycosylation modifications, among which O-acetylation of N-acetyl neuraminic acid (Neu5Ac) is the most common in mammalian cells. Isoforms of sialic acid are critical determinants of virus pathogenesis. To date, the focus of viral receptor-mediated attachment has been on Neu5Ac. O-Acetylated Neu5Acs have been largely ignored as receptor determinants of virus pathogenesis, although it is ubiquitous across species. Significantly, the array of structures resulting from site-specific O-acetylation by sialic acid O-acetyltransferases (SOATs) provides a means to examine specificity of viral binding to host cells. Specifically, C(4) O-acetylated Neu5Ac can influence virus pathogenicity. However, the biological implications of only O-acetylated Neu5Ac at C(7–9) have been explored extensively. This review will highlight the biological significance, extraction methods, and synthetic modifications of C(4) O-acetylated Neu5Ac that may provide value in therapeutic developments and targets to prevent virus related diseases.",2019 Nov 1,"Park, Simon S.",Vaccines (Basel),,,True
29ffe6751373335a54c9d02cec1af4cfdf049ea8,PMC,A Single and Un-Adjuvanted Dose of a Chimpanzee Adenovirus-Vectored Vaccine against Chikungunya Virus Fully Protects Mice from Lethal Disease,http://dx.doi.org/10.3390/pathogens8040231,PMC6963200,31718104,CC BY,"The mosquito-borne chikungunya virus (CHIKV) has become a major global health problem. Upon infection, chikungunya fever (CHIKF) can result in long-term joint pain and arthritis, and despite intense research, no licensed vaccine for CHIKV is available. We have developed two recombinant chimpanzee adenovirus-vectored vaccines (ChAdOx1) that induce swift and robust anti-CHIKV immune responses with a single dose, without the need for adjuvants or booster vaccines. Here, we report the vaccines’ protective efficacies against CHIKV infection in a lethal A129 mouse model. Our results indicate that a single, un-adjuvanted ChAdOx1 Chik or ChAdOx1 Chik ΔCap dose provided complete protection against a lethal virus challenge and prevented CHIKV-associated severe inflammation. These candidate vaccines supported survival equal to the attenuated 181/25 CHIKV reference vaccine but without the vaccine-related side effects, such as weight loss. Vaccination with either ChAdOx1 Chik or ChAdOx1 Chik ΔCap resulted in high titers of neutralizing antibodies that are associated with protection, indicating that the presence of the capsid within the vaccine construct may not be essential to afford protection under the conditions tested. We conclude that both replication-deficient ChAdOx1 Chik vaccines are safe even when used in A129 mice and afford complete protection from a lethal challenge.",2019 Nov 12,"['Campos, Rafael Kroon', 'Preciado-Llanes, Lorena', 'Azar, Sasha R.', 'Lopez-Camacho, Cesar', 'Reyes-Sandoval, Arturo', 'Rossi, Shannan L.']",Pathogens,,,True
f8fe842dd87dd363a218e07c79e0dcfeb60a32d2,PMC,A Single and Un-Adjuvanted Dose of a Chimpanzee Adenovirus-Vectored Vaccine against Chikungunya Virus Fully Protects Mice from Lethal Disease,http://dx.doi.org/10.3390/pathogens8040231,PMC6963200,31718104,CC BY,"The mosquito-borne chikungunya virus (CHIKV) has become a major global health problem. Upon infection, chikungunya fever (CHIKF) can result in long-term joint pain and arthritis, and despite intense research, no licensed vaccine for CHIKV is available. We have developed two recombinant chimpanzee adenovirus-vectored vaccines (ChAdOx1) that induce swift and robust anti-CHIKV immune responses with a single dose, without the need for adjuvants or booster vaccines. Here, we report the vaccines’ protective efficacies against CHIKV infection in a lethal A129 mouse model. Our results indicate that a single, un-adjuvanted ChAdOx1 Chik or ChAdOx1 Chik ΔCap dose provided complete protection against a lethal virus challenge and prevented CHIKV-associated severe inflammation. These candidate vaccines supported survival equal to the attenuated 181/25 CHIKV reference vaccine but without the vaccine-related side effects, such as weight loss. Vaccination with either ChAdOx1 Chik or ChAdOx1 Chik ΔCap resulted in high titers of neutralizing antibodies that are associated with protection, indicating that the presence of the capsid within the vaccine construct may not be essential to afford protection under the conditions tested. We conclude that both replication-deficient ChAdOx1 Chik vaccines are safe even when used in A129 mice and afford complete protection from a lethal challenge.",2019 Nov 12,"['Campos, Rafael Kroon', 'Preciado-Llanes, Lorena', 'Azar, Sasha R.', 'Lopez-Camacho, Cesar', 'Reyes-Sandoval, Arturo', 'Rossi, Shannan L.']",Pathogens,,,False
ac8b5e9b4a49a1062eddf4fc48a19778e66e9a78,PMC,The Interplay between Dengue Virus and the Human Innate Immune System: A Game of Hide and Seek,http://dx.doi.org/10.3390/vaccines7040145,PMC6963221,31658677,CC BY,"With 40% of the world population at risk, infections with dengue virus (DENV) constitute a serious threat to public health. While there is no antiviral therapy available against this potentially lethal disease, the efficacy of the only approved vaccine is not optimal and its safety has been recently questioned. In order to develop better vaccines based on attenuated and/or chimeric viruses, one must consider how the human immune system is engaged during DENV infection. The activation of the innate immunity through the detection of viruses by cellular sensors is the first line of defence against those pathogens. This triggers a cascade of events which establishes an antiviral state at the cell level and leads to a global immunological response. However, DENV has evolved to interfere with the innate immune signalling at multiple levels, hence dampening antiviral responses and favouring viral replication and dissemination. This review elaborates on the interplay between DENV and the innate immune system. A special focus is given on the viral countermeasure mechanisms reported over the last decade which should be taken into consideration during vaccine development.",2019 Oct 10,"['Tremblay, Nicolas', 'Freppel, Wesley', 'Sow, Aïssatou Aïcha', 'Chatel-Chaix, Laurent']",Vaccines (Basel),,,True
02a29bd2f39ecdbbb5e51a003c0bc7818029f384,PMC,A Recombinant Influenza A/H1N1 Carrying A Short Immunogenic Peptide of MERS-CoV as Bivalent Vaccine in BALB/c Mice,http://dx.doi.org/10.3390/pathogens8040281,PMC6963271,31810359,CC BY,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) became a global human health threat since its first documentation in humans in 2012. An efficient vaccine for the prophylaxis of humans in hotspots of the infection (e.g., Saudi Arabia) is necessary but no commercial vaccines are yet approved. In this study, a chimeric DNA construct was designed to encode an influenza A/H1N1 NA protein which is flanking immunogenic amino acids (aa) 736–761 of MERS-CoV spike protein. Using the generated chimeric construct, a novel recombinant vaccine strain against pandemic influenza A virus (H1N1pdm09) and MERS-CoV was generated (chimeric bivalent 5 + 3). The chimeric bivalent 5 + 3 vaccine strain comprises a recombinant PR8-based vaccine, expressing the PB1, HA, and chimeric NA of pandemic 2009 H1N1. Interestingly, an increase in replication efficiency of the generated vaccine strain was observed when compared to the PR8-based 5 + 3 H1N1pdm09 vaccine strain that lacks the MERS-CoV spike peptide insert. In BALB/c mice, the inactivated chimeric bivalent vaccine induced potent and specific neutralizing antibodies against MERS-CoV and H1N1pdm09. This novel approach succeeded in developing a recombinant influenza virus with potential use as a bivalent vaccine against H1N1pdm09 and MERS-CoV. This approach provides a basis for the future development of chimeric influenza-based vaccines against MERS-CoV and other viruses.",2019 Dec 2,"['Shehata, Mahmoud M.', 'Kandeil, Ahmed', 'Mostafa, Ahmed', 'Mahmoud, Sara H.', 'Gomaa, Mokhtar R.', 'El-Shesheny, Rabeh', 'Webby, Richard', 'Kayali, Ghazi', 'A. Ali, Mohamed']",Pathogens,,,True
0899b0f8df5f20c6a46ba1dc7675c85858b59a68,PMC,Recombinant Lactobacillus casei Expressing Capsid Protein VP60 can Serve as Vaccine Against Rabbit Hemorrhagic Disease Virus in Rabbits,http://dx.doi.org/10.3390/vaccines7040172,PMC6963290,31684059,CC BY,"Rabbit hemorrhagic disease virus (RHDV) is the causative agent of rabbit hemorrhagic disease (RHD). RHD, characterized by hemorrhaging, liver necrosis, and high morbidity and mortality in rabbits and hares, causes severe economic losses in the rabbit industry worldwide. Due to the lack of an efficient in-vitro propagation system for RHDV, the current vaccine is produced via chemical inactivation of crude RHDV preparation derived from the livers of infected rabbits. Inactivated vaccines are effective for controlling RHD, but the potential problems of biosafety and animal welfare have negative effects on the application of inactivated vaccines. In this study, an oral Lactobacillus casei (L. casei) vaccine was used as an antigen delivery system to express RHDV capsid protein VP60(VP1)-eGFP fusion protein. The expression of the recombinant protein was confirmed via western blotting and immunofluorescence (IFA). Our results indicate that oral administration of this probiotic vaccine can stimulate secretory immunoglobulin A (SIgA)-based mucosal and IgG-based humoral immune responses in rabbits. The immunized rabbits were completely protected against challenge with RHDV. Our findings indicate that the L. casei expression system is a new strategy for the development of a safe and efficient vaccine against RHDV.",2019 Nov 2,"['Wang, Li', 'Xia, Tian', 'Guo, Tiantian', 'Ru, Yi', 'Jiang, Yanping', 'Cui, Wen', 'Zhou, Han', 'Qiao, Xinyuan', 'Tang, Lijie', 'Xu, Yigang', 'Li, Yijing']",Vaccines (Basel),,,True
d213253353b62aa454d0bb02a7651a0ef7c0d34f,PMC,Vaccination against Paediatric Respiratory Pathogens,http://dx.doi.org/10.3390/vaccines7040168,PMC6963365,31683882,CC BY,"Acute respiratory infections (ARIs) are extremely common in children, especially those under 5 years old. They can lead to complications, super-infection, respiratory failure, and even compromised respiratory function in adulthood. For some of the responsible pathogens, vaccines are available. This review reports current issues about vaccines against the main respiratory pathogens to highlight the available strategies to reduce the burden of paediatric respiratory disease. The optimal use of influenza, pneumococcal, pertussis and measles vaccines is required in order to reduce ARI burden. Vaccination coverage rates must be improved to achieve the full benefits of these vaccines. Recently, advances in the knowledge of respiratory syncytial virus structural biology and immunology as well as the development of new techniques to generate vaccine candidates have increased the number of promising vaccines even against this harmful pathogen.",2019 Nov 1,"['Bianchini, Sonia', 'Argentiero, Alberto', 'Camilloni, Barbara', 'Silvestri, Ettore', 'Alunno, Anna', 'Esposito, Susanna']",Vaccines (Basel),,,True
306d48f87402c3759c22d1c5fbfe4ddce3fd5967,PMC,Antimicrobial Stewardship Programs in Community Health Systems Perceived by Physicians and Pharmacists: A Qualitative Study with Gap Analysis,http://dx.doi.org/10.3390/antibiotics8040252,PMC6963390,31817468,CC BY,"Antimicrobial stewardship program (ASP) is one of the most important strategies for managing infectious disease treatment and preventing antimicrobial resistance. The successful implementation of ASP in the community health system (CHS) has been challenging. We evaluated perceptions of current ASP, potential setbacks of ASP implementation, and future demands on ASP services among physicians and pharmacists in the CHS. The qualitative research was conducted through in-depth individual interviews and focus group discussions with 11 physicians and 11 pharmacists. In addition, a quantitative gap analysis was conducted to assess the different awareness and demands on services of ASP and preferred antimicrobial-related problems (ARP). In overall, perceptions of ASP varied by profession. The identified setbacks were unorganized institutional leadership, the undefined roles of healthcare professionals, a lack of reimbursement, the hierarchical structure of the health system, and the labor-intensive working environment of pharmacy services. Although demands for ASP improvement were similar among professionals, they had different preferences in prioritizing each service item of ASP/ARP development and the profession responsible for each service. Continuous administrative and financial investments, understanding ASP contents, ASP-specific information technology, and interdisciplinary collaboration with good communication among healthcare professions are needed to continue the progression of ASP.",2019 Dec 5,"['Park, Sohyun', 'Kang, Ji Eun', 'Choi, Hee Jung', 'Kim, Chung-Jong', 'Chung, Eun Kyoung', 'Kim, Sun Ah', 'Rhie, Sandy Jeong']",Antibiotics (Basel),,,True
014d7df59dc6c5ed456bf19b76b394e920d3a9dc,PMC,Entry of Scotophilus Bat Coronavirus-512 and Severe Acute Respiratory Syndrome Coronavirus in Human and Multiple Animal Cells,http://dx.doi.org/10.3390/pathogens8040259,PMC6963420,31766704,CC BY,"Bats are natural reservoirs of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV). Scotophilus bat CoV-512 demonstrates potential for cross-species transmission because its viral RNA and specific antibodies have been detected in three bat species of Taiwan. Understanding the cell tropism of Scotophilus bat CoV-512 is the first step for studying the mechanism of cross-species transmission. In this study, a lentivirus-based pseudovirus was produced using the spike (S) protein of Scotophilus bat CoV-512 or SARS-CoV as a surface protein to test the interaction between coronaviral S protein and its cell receptor on 11 different cells. Susceptible cells expressed red fluorescence protein (RFP) after the entry of RFP-bound green fluorescence protein (GFP)-fused S protein of Scotophilus bat CoV-512 (RFP-Sco-S-eGFP) or RFP-SARS-S pseudovirus, and firefly luciferase (FLuc) activity expressed by cells infected with FLuc-Sco-S-eGFP or FLuc-SARS-S pseudovirus was quantified. Scotophilus bat CoV-512 pseudovirus had significantly higher entry efficiencies in Madin Darby dog kidney epithelial cells (MDCK), black flying fox brain cells (Pabr), and rat small intestine epithelial cells (IEC-6). SARS-CoV pseudovirus had significantly higher entry efficiencies in human embryonic kidney epithelial cells (HEK-293T), pig kidney epithelial cells (PK15), and MDCK cells. These findings demonstrated that Scotophilus bat CoV-512 had a broad host range for cross-species transmission like SARS-CoV.",2019 Nov 22,"['Chen, Yi-Ning', 'Hsu, Hsiao-Chin', 'Wang, Sheng-Wei', 'Lien, Hao-Chiang', 'Lu, Hsin-Ti', 'Peng, Sheng-Kai']",Pathogens,,,True
7242f572560ed67b41d262669f2dc343d268eb58,PMC,Entry of Scotophilus Bat Coronavirus-512 and Severe Acute Respiratory Syndrome Coronavirus in Human and Multiple Animal Cells,http://dx.doi.org/10.3390/pathogens8040259,PMC6963420,31766704,CC BY,"Bats are natural reservoirs of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV). Scotophilus bat CoV-512 demonstrates potential for cross-species transmission because its viral RNA and specific antibodies have been detected in three bat species of Taiwan. Understanding the cell tropism of Scotophilus bat CoV-512 is the first step for studying the mechanism of cross-species transmission. In this study, a lentivirus-based pseudovirus was produced using the spike (S) protein of Scotophilus bat CoV-512 or SARS-CoV as a surface protein to test the interaction between coronaviral S protein and its cell receptor on 11 different cells. Susceptible cells expressed red fluorescence protein (RFP) after the entry of RFP-bound green fluorescence protein (GFP)-fused S protein of Scotophilus bat CoV-512 (RFP-Sco-S-eGFP) or RFP-SARS-S pseudovirus, and firefly luciferase (FLuc) activity expressed by cells infected with FLuc-Sco-S-eGFP or FLuc-SARS-S pseudovirus was quantified. Scotophilus bat CoV-512 pseudovirus had significantly higher entry efficiencies in Madin Darby dog kidney epithelial cells (MDCK), black flying fox brain cells (Pabr), and rat small intestine epithelial cells (IEC-6). SARS-CoV pseudovirus had significantly higher entry efficiencies in human embryonic kidney epithelial cells (HEK-293T), pig kidney epithelial cells (PK15), and MDCK cells. These findings demonstrated that Scotophilus bat CoV-512 had a broad host range for cross-species transmission like SARS-CoV.",2019 Nov 22,"['Chen, Yi-Ning', 'Hsu, Hsiao-Chin', 'Wang, Sheng-Wei', 'Lien, Hao-Chiang', 'Lu, Hsin-Ti', 'Peng, Sheng-Kai']",Pathogens,,,False
e0e8ee783d4c465b22a44cb27e7e0f1b0d073245,PMC,Significant Interference with Porcine Epidemic Diarrhea Virus Pandemic and Classical Strain Replication in Small-Intestine Epithelial Cells Using an shRNA Expression Vector,http://dx.doi.org/10.3390/vaccines7040173,PMC6963423,31684062,CC BY,"Porcine epidemic diarrhea (PED) re-emerged in China in 2010 and is now widespread. Evidence indicates that highly virulent porcine epidemic diarrhea virus (PEDV) strains belonging to genotype G2 caused a large-scale outbreak of diarrhea. Currently, vaccines derived from PEDV classical strains do not effectively prevent infection by virulent PEDV strains, and no specific drug is available to treat the disease. RNA interference (RNAi) is a novel and effective way to cure a wide range of viruses. We constructed three short hairpin RNA (shRNA)-expressing plasmids (shR-N307, shR-N463, and shR-N1071) directed against nucleocapsid (N) and determined their antiviral activities in intestine epithelial cells infected with a classical CV777 strain and LNCT2. We verified that shR-N307, shR-N463, and shR-N1071 effectively inhibited the expression of the transfected N gene in vitro, comparable to the control shRNA. We further demonstrated the shRNAs markedly reduced PEDV CV777 and LNCT2 replication upon downregulation of N production. Therefore, this study provides a new strategy for the design of antiviral methods against coronaviruses by targeting their processivity factors.",2019 Nov 2,"['Shi, Da', 'Wang, Xiaobo', 'Shi, Hongyan', 'Zhang, Jiyu', 'Han, Yuru', 'Chen, Jianfei', 'Zhang, Xin', 'Liu, Jianbo', 'Zhang, Jialin', 'Ji, Zhaoyang', 'Jing, Zhaoyang', 'Feng, Li']",Vaccines (Basel),,,True
8f8bd6796570957dcf2c62e70faa1f1ca3769182,PMC,"Analysis of Resistance of Ebola Virus Glycoprotein-Driven Entry Against MDL28170, An Inhibitor of Cysteine Cathepsins",http://dx.doi.org/10.3390/pathogens8040192,PMC6963435,31618932,CC BY,"Ebola virus (EBOV) infection can cause severe and frequently fatal disease in human patients. The EBOV glycoprotein (GP) mediates viral entry into host cells. For this, GP depends on priming by the pH-dependent endolysosomal cysteine proteases cathepsin B (CatB) and, to a lesser degree, cathepsin L (CatL), at least in most cell culture systems. However, there is limited information on whether and how EBOV-GP can acquire resistance to CatB/L inhibitors. Here, we addressed this question using replication-competent vesicular stomatitis virus bearing EBOV-GP. Five passages of this virus in the presence of the CatB/CatL inhibitor MDL28170 were sufficient to select resistant viral variants and sequencing revealed that all GP sequences contained a V37A mutation, which, in the context of native GP, is located in the base of the GP surface unit. In addition, some GP sequences harbored mutation S195R in the receptor-binding domain. Finally, mutational analysis demonstrated that V37A but not S195R conferred resistance against MDL28170 and other CatB/CatL inhibitors. Collectively, a single amino acid substitution in GP is sufficient to confer resistance against CatB/CatL inhibitors, suggesting that usage of CatB/CatL inhibitors for antiviral therapy may rapidly select for resistant viral variants.",2019 Oct 15,"['Hoffmann, Markus', 'Kaufmann, Svenja Victoria', 'Fischer, Carina', 'Maurer, Wiebke', 'Moldenhauer, Anna-Sophie', 'Pöhlmann, Stefan']",Pathogens,,,True
14626b4b98947a5534bdcc578b6659c258f7e7dd,PMC,Immunogenicity and Protection from Receptor-Binding Domains of Toxins as Potential Vaccine Candidates for Clostridium difficile,http://dx.doi.org/10.3390/vaccines7040180,PMC6963439,31717334,CC BY,"The receptor-binding domains (RBDs) located in toxin A and toxin B of Clostridium difficile are known to be nontoxic and immunogenic. We need to develop a new type vaccine based on RBDs. In this study, we expressed and purified recombinant proteins (named RBD-TcdA and RBD-TcdB) as vaccine candidates containing the RBDs of toxin A and toxin B, respectively, from the C. difficile reference strain VPI10463. The immunogenicity and protection of the vaccine candidates RBD-TcdA, RBD-TcdB, and RBD-TcdA/B was evaluated by ELISA and survival assays. The data indicated that mice immunized with all vaccine candidates displayed potent levels of RBD-specific serum IgG. Following intramuscular immunization of mice with RBD-TcdA and/or RBD-TcdB, these vaccine candidates triggered immune responses that protected mice compared to mice immunized with aluminum hydroxide alone. Taken together, the results of this study reveal that recombinant proteins containing RBDs of C. difficile toxins can be used for vaccine development. Additionally, we found that an RBD-TcdA/B vaccine can elicit a stronger humoral immune response and provide better immunoprotection than the univalent vaccines. This RBD vaccine candidate conferred significant protection against disease symptoms and death caused by toxins from a wild-type C. difficile strain.",2019 Nov 8,"['Luo, Deyan', 'Liu, Xuechao', 'Xing, Li', 'Sun, Yakun', 'Huang, Jie', 'Zhang, Liangyan', 'Li, Jiajia', 'Wang, Hui']",Vaccines (Basel),,,True
5947b4f84c6a5a8b5aa552794cdafd1943615f26,PMC,Immunogenicity and Protection from Receptor-Binding Domains of Toxins as Potential Vaccine Candidates for Clostridium difficile,http://dx.doi.org/10.3390/vaccines7040180,PMC6963439,31717334,CC BY,"The receptor-binding domains (RBDs) located in toxin A and toxin B of Clostridium difficile are known to be nontoxic and immunogenic. We need to develop a new type vaccine based on RBDs. In this study, we expressed and purified recombinant proteins (named RBD-TcdA and RBD-TcdB) as vaccine candidates containing the RBDs of toxin A and toxin B, respectively, from the C. difficile reference strain VPI10463. The immunogenicity and protection of the vaccine candidates RBD-TcdA, RBD-TcdB, and RBD-TcdA/B was evaluated by ELISA and survival assays. The data indicated that mice immunized with all vaccine candidates displayed potent levels of RBD-specific serum IgG. Following intramuscular immunization of mice with RBD-TcdA and/or RBD-TcdB, these vaccine candidates triggered immune responses that protected mice compared to mice immunized with aluminum hydroxide alone. Taken together, the results of this study reveal that recombinant proteins containing RBDs of C. difficile toxins can be used for vaccine development. Additionally, we found that an RBD-TcdA/B vaccine can elicit a stronger humoral immune response and provide better immunoprotection than the univalent vaccines. This RBD vaccine candidate conferred significant protection against disease symptoms and death caused by toxins from a wild-type C. difficile strain.",2019 Nov 8,"['Luo, Deyan', 'Liu, Xuechao', 'Xing, Li', 'Sun, Yakun', 'Huang, Jie', 'Zhang, Liangyan', 'Li, Jiajia', 'Wang, Hui']",Vaccines (Basel),,,False
424ea1927a270902bd78e27db83dd9411b4ea9a6,PMC,Differential Immune Responses to Hemorrhagic Fever-Causing Arenaviruses,http://dx.doi.org/10.3390/vaccines7040138,PMC6963578,31581720,CC BY,"The family Arenaviridae contains several pathogens of major clinical importance. The Old World (OW) arenavirus Lassa virus is endemic in West Africa and is estimated to cause up to 300,000 infections each year. The New World (NW) arenaviruses Junín and Machupo periodically cause hemorrhagic fever outbreaks in South America. While these arenaviruses are highly pathogenic in humans, recent evidence indicates that pathogenic OW and NW arenaviruses interact with the host immune system differently, which may have differential impacts on viral pathogenesis. Severe Lassa fever cases are characterized by profound immunosuppression. In contrast, pathogenic NW arenavirus infections are accompanied by elevated levels of Type I interferon and pro-inflammatory cytokines. This review aims to summarize recent findings about interactions of these pathogenic arenaviruses with the innate immune machinery and the subsequent effects on adaptive immunity, which may inform the development of vaccines and therapeutics against arenavirus infections.",2019 Oct 2,"['Mantlo, Emily', 'Paessler, Slobodan', 'Huang, Cheng']",Vaccines (Basel),,,True
71e571db52c00a9c67fffc6f075580fe0732cde1,PMC,Effects of Adjuvants on the Immunogenicity and Efficacy of a Zika Virus Envelope Domain III Subunit Vaccine,http://dx.doi.org/10.3390/vaccines7040161,PMC6963592,31717890,CC BY,"Zika virus (ZIKV), a mosquito-borne flavivirus, has attracted global attention due to its close association with congenital Zika syndrome and neurological diseases, and transmission through additional routes, such as sexual contact. Currently there are no vaccines approved for ZIKV, and thus, there is an urgent need to develop an effective and safe ZIKV vaccine. Domain III (DIII) of the ZIKV envelope (E) protein is an important vaccine target, and a vaccine developed using a mutant DIII of E (EDIII) protein protects adult and pregnant mice, and unborn offspring, against ZIKV infection. Here, we have used immunocompetent BALB/c mice treated with anti-interferon-α/β receptor 1 (Ifnar1) antibodies to investigate whether three adjuvants (aluminum (Alum), monophosphoryl lipid A (MPL), and MF59), either alone or in combination, could improve the efficacy of this EDIII subunit vaccine. Our data show that, although vaccine formulated with a single adjuvant induced a specific antibody and cellular immune response, and reduced viral load in mice challenged with ZIKV, the combination of Alum and MPL adjuvants led to a more robust and balanced immune response, stronger neutralizing activity against three recent ZIKV human strains, and greater protection against a high-dose ZIKV challenge. Particularly, the combination of Alum with MPL significantly reduced viral titers and viral RNA copy numbers in sera and tissues, including the male reproductive organs. Overall, this study has identified the combination of Alum and MPL as the most effective adjuvant for ZIKV EDIII subunit vaccines, and it has important implications for subunit vaccines against other enveloped viruses, including non-ZIKV flaviviruses.",2019 Oct 27,"['Wang, Xinyi', 'Tai, Wanbo', 'Zhang, Xiaolu', 'Zhou, Yusen', 'Du, Lanying', 'Shen, Chuanlai']",Vaccines (Basel),,,True
328b36edcc6169a2aceba2c7e6859d1770d6a81d,PMC,"Combating Antimicrobial Resistance in Singapore: A Qualitative Study Exploring the Policy Context, Challenges, Facilitators, and Proposed Strategies",http://dx.doi.org/10.3390/antibiotics8040201,PMC6963657,31671826,CC BY,"Antimicrobial resistance (AMR) is a global public health threat that warrants urgent attention. However, the multifaceted nature of AMR often complicates the development and implementation of comprehensive policies. In this study, we describe the policy context and explore experts’ perspectives on the challenges, facilitators, and strategies for combating AMR in Singapore. We conducted semi-structured interviews with 21 participants. Interviews were transcribed verbatim and were analyzed thematically, adopting an interpretative approach. Participants reported that the Ministry of Health (MOH) has effectively funded AMR control programs and research in all public hospitals. In addition, a preexisting One Health platform, among MOH, Agri-Food & Veterinary Authority (restructured to form the Singapore Food Agency and the Animal & Veterinary Service under NParks in April 2019), National Environment Agency, and Singapore’s National Water Agency, was perceived to have facilitated the coordination and formulation of Singapore’s AMR strategies. Nonetheless, participants highlighted that the success of AMR strategies is compounded by various challenges such as surveillance in private clinics, resource constraints at community-level health facilities, sub-optimal public awareness, patchy regulation on antimicrobial use in animals, and environmental contamination. This study shows that the process of planning and executing AMR policies is complicated even in a well-resourced country such as Singapore. It has also highlighted the increasing need to address the social, political, cultural, and behavioral aspects influencing AMR. Ultimately, it will be difficult to design policy interventions that cater for the needs of individuals, families, and the community, unless we understand how all these aspects interact and shape the AMR response.",2019 Oct 29,"['Singh, Shweta Rajkumar', 'Chua, Alvin Qijia', 'Tan, Sok Teng', 'Tam, Clarence C.', 'Hsu, Li Yang', 'Legido-Quigley, Helena']",Antibiotics (Basel),,,True
e984ba610fad579e96c611e869274dd3b8deb77e,PMC,"Combating Antimicrobial Resistance in Singapore: A Qualitative Study Exploring the Policy Context, Challenges, Facilitators, and Proposed Strategies",http://dx.doi.org/10.3390/antibiotics8040201,PMC6963657,31671826,CC BY,"Antimicrobial resistance (AMR) is a global public health threat that warrants urgent attention. However, the multifaceted nature of AMR often complicates the development and implementation of comprehensive policies. In this study, we describe the policy context and explore experts’ perspectives on the challenges, facilitators, and strategies for combating AMR in Singapore. We conducted semi-structured interviews with 21 participants. Interviews were transcribed verbatim and were analyzed thematically, adopting an interpretative approach. Participants reported that the Ministry of Health (MOH) has effectively funded AMR control programs and research in all public hospitals. In addition, a preexisting One Health platform, among MOH, Agri-Food & Veterinary Authority (restructured to form the Singapore Food Agency and the Animal & Veterinary Service under NParks in April 2019), National Environment Agency, and Singapore’s National Water Agency, was perceived to have facilitated the coordination and formulation of Singapore’s AMR strategies. Nonetheless, participants highlighted that the success of AMR strategies is compounded by various challenges such as surveillance in private clinics, resource constraints at community-level health facilities, sub-optimal public awareness, patchy regulation on antimicrobial use in animals, and environmental contamination. This study shows that the process of planning and executing AMR policies is complicated even in a well-resourced country such as Singapore. It has also highlighted the increasing need to address the social, political, cultural, and behavioral aspects influencing AMR. Ultimately, it will be difficult to design policy interventions that cater for the needs of individuals, families, and the community, unless we understand how all these aspects interact and shape the AMR response.",2019 Oct 29,"['Singh, Shweta Rajkumar', 'Chua, Alvin Qijia', 'Tan, Sok Teng', 'Tam, Clarence C.', 'Hsu, Li Yang', 'Legido-Quigley, Helena']",Antibiotics (Basel),,,False
0ae65070d7cbfa7b5454181af026a8ea7391d5d2,PMC,Assessment of Immunogenicity and Efficacy of a Zika Vaccine Using Modified Vaccinia Ankara Virus as Carriers,http://dx.doi.org/10.3390/pathogens8040216,PMC6963679,31684117,CC BY,"Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has spread to more than 70 countries worldwide since 2015. Despite active research, there are currently no licensed vaccines or therapeutics. We have previously reported the development of various adenoviral vectored vaccine candidates (ChAdOx1 ZIKV) with the ability to stimulate effective immunity in mice and provide protection upon a ZIKV challenge model, using a non-adjuvanted single vaccination approach. In this study, we constructed various modified vaccinia Ankara (MVA) viruses to express the ZIKV Envelope (E) with modifications on the precursor membrane (prM) or on the C-terminus envelope transmembrane domain (TM), similar to our ChAdOx1 vaccine candidates. MVA-ZIKV vaccine candidates were evaluated as a non-adjuvanted single vaccination regimen against a ZIKV Brazilian isolate, using viraemia as the correlate of protection. Here, we report the induction of a modest level of anti-ZIKV E antibodies by all MVA vectored vaccines and sub-optimal efficacy in a ZIKV challenge model. Our results indicate the requirement of additional strategies when using MVA-ZIKV vaccines to afford sterile protection upon a non-adjuvanted and single vaccination regime.",2019 Nov 2,"['López-Camacho, César', 'Kim, Young Chan', 'Abbink, Peter', 'Larocca, Rafael A.', 'Huiskonen, Juha T.', 'Barouch, Dan H.', 'Reyes-Sandoval, Arturo']",Pathogens,,,True
a912f654028e787673b235c9ba2eb2d161e372aa,PMC,Endocytic Pathway of Feline Coronavirus for Cell Entry: Differences in Serotype-Dependent Viral Entry Pathway,http://dx.doi.org/10.3390/pathogens8040300,PMC6963708,31888266,CC BY,"Feline coronavirus (FCoV) is a pathogen causing a lethal infectious disease in cats, feline infectious peritonitis. It has two serotypes (type I FCoV and type II FCoV). According to our previous study, type I FCoV infection is inhibited by compounds inducing intracellular cholesterol accumulation, whereas type II FCoV infection is not inhibited. Intracellular cholesterol accumulation was reported to disrupt late endosome function. Based on these findings, types I and II FCoV are considered to enter the cytosol through late and early endosomes, respectively. We investigated whether the antiviral activities of a late endosome trafficking inhibitor and cholesterol-accumulating agents are different between the FCoV serotypes. The late endosome trafficking inhibitor did not inhibit type II FCoV infection, but it inhibited type I FCoV infection. Type I FCoV infection was inhibited by cholesterol-accumulating triazoles, but not by non-cholesterol-accumulating triazoles. These phenomena were observed in both feline cell lines and feline primary macrophages. This study provides additional information on the differences in intracellular reproductive cycle between type I and type II FCoV.",2019 Dec 16,"['Takano, Tomomi', 'Wakayama, Yumeho', 'Doki, Tomoyoshi']",Pathogens,,,True
546de9ee7a4ee26a482af31e1b374ee85242e0c5,PMC,Engineering a Novel Antibody-Peptide Bispecific Fusion Protein Against MERS-CoV,http://dx.doi.org/10.3390/antib8040053,PMC6963733,31690009,CC BY,"In recent years, tremendous efforts have been made in the engineering of bispecific or multi-specific antibody-based therapeutics by combining two or more functional antigen-recognizing elements into a single construct. However, to the best of our knowledge there has been no reported cases of effective antiviral antibody-peptide bispecific fusion proteins. We previously developed potent fully human monoclonal antibodies and inhibitory peptides against Middle East Respiratory Syndrome Coronavirus (MERS-CoV), a novel coronavirus that causes severe acute respiratory illness with high mortality. Here, we describe the generation of antibody-peptide bispecific fusion proteins, each of which contains an anti-MERS-CoV single-chain antibody m336 (or normal human IgG1 CH3 domain as a control) linked with, or without, a MERS-CoV fusion inhibitory peptide HR2P. We found that one of these fusion proteins, designated as m336 diabody-pep, exhibited more potent inhibitory activity than the antibody or the peptide alone against pseudotyped MERS-CoV infection and MERS-CoV S protein-mediated cell-cell fusion, suggesting its potential to be developed as an effective bispecific immunotherapeutic for clinical use.",2019 Nov 4,"['Wang, Lili', 'Xu, Jiyan', 'Kong, Yu', 'Liang, Ruiying', 'Li, Wei', 'Li, Jinyao', 'Lu, Jun', 'Dimitrov, Dimiter S.', 'Yu, Fei', 'Wu, Yanling', 'Ying, Tianlei']",Antibodies (Basel),,,True
85efed2c84dba208203669ef115bb9dc750e24c1,PMC,Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans,http://dx.doi.org/10.3390/pathogens8040168,PMC6963926,31574965,CC BY,"A large number of human genes associated with viral infections contain single nucleotide polymorphisms (SNPs), which represent a genetic variation caused by the change of a single nucleotide in the DNA sequence. SNPs are located in coding or non-coding genomic regions and can affect gene expression or protein function by different mechanisms. Furthermore, they have been linked to multiple human diseases, highlighting their medical relevance. Therefore, the identification and analysis of this kind of polymorphisms in the human genome has gained high importance in the research community, and an increasing number of studies have been published during the last years. As a consequence of this exhaustive exploration, an association between the presence of some specific SNPs and the susceptibility or severity of many infectious diseases in some risk population groups has been found. In this review, we discuss the relevance of SNPs that are important to understand the pathology derived from influenza A virus (IAV) infections in humans and the susceptibility of some individuals to suffer more severe symptoms. We also discuss the importance of SNPs for IAV vaccine effectiveness.",2019 Sep 30,"['Nogales, Aitor', 'L. DeDiego, Marta']",Pathogens,,,True
185e505daa1da8ee7ece18212693b2550410a190,PMC,In vivo rescue of recombinant Zika virus from an infectious cDNA clone and its implications in vaccine development,http://dx.doi.org/10.1038/s41598-020-57545-2,PMC6965646,31949262,CC BY,"Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family that has been known to circulate for decades causing mild febrile illness. The more recent ZIKV outbreaks in the Americas and the Caribbean associated with congenital malformations and Guillain-Barré syndrome in adults have placed public health officials in high alert and highlight the significant impact of ZIKV on human health. New technologies to study the biology of ZIKV and to develop more effective prevention options are highly desired. In this study we demonstrate that direct delivery in mice of an infectious ZIKV cDNA clone allows the rescue of recombinant (r)ZIKV in vivo. A bacterial artificial chromosome containing the sequence of ZIKV strain Paraiba/2015 under the control of the cytomegalovirus promoter was complexed with a commercial transfection reagent and administrated using different routes in type-I interferon receptor deficient A129 mice. Clinical signs and death associated with ZIKV viremia were observed in mice. The rZIKV recovered from these mice remained fully virulent in a second passage in mice. Interestingly, infectious rZIKV was also recovered after intraperitoneal inoculation of the rZIKV cDNA in the absence of transfection reagent. Further expanding these studies, we demonstrate that a single intraperitoneal inoculation of a cDNA clone encoding an attenuated rZIKV was safe, highly immunogenic, and provided full protection against lethal ZIKV challenge. This novel in vivo reverse genetics method is a potentially suitable delivery platform for the study of wild-type and live-attenuated ZIKV devoid of confounding factors typical associated with in vitro systems. Moreover, our results open the possibility of employing similar in vivo reverse genetic approaches for the generation of other viruses and, therefore, change the way we will use reverse genetics in the future.",2020 Jan 16,"['Ávila-Pérez, Gines', 'Nogales, Aitor', 'Park, Jun-Gyu', 'Vasquez, Desarey Morales', 'Dean, David A.', 'Barravecchia, Michael', 'Perez, Daniel R.', 'Almazán, Fernando', 'Martínez-Sobrido, Luis']",Sci Rep,,,True
c3de717508f4b790f53e9e998ef61c5f27b00ce7,PMC,Strategies to Target Specific Components of the Ubiquitin Conjugation/Deconjugation Machinery,http://dx.doi.org/10.3389/fchem.2019.00914,PMC6966607,31998698,CC BY,"The regulation of ubiquitination status in the cell is controlled by ubiquitin ligases acting in tandem with deubiquitinating enzymes. Ubiquitination controls many key processes in the cell from division to death making its tight regulation key to optimal cell function. Activity based protein profiling has emerged as a powerful technique to study these important enzymes. With around 100 deubiquitinating enzymes and 600 ubiquitin ligases in the human genome targeting a subclass of these enzymes or even a single enzyme is a compelling strategy to unpick this complex system. In this review we will discuss different approaches adopted, including activity-based probes centered around ubiquitin-protein, ubiquitin-peptide and mutated ubiquitin scaffolds. We examine challenges faced and opportunities presented to increase specificity in activity-based protein profiling of the ubiquitin conjugation/deconjugation machinery.",2020 Jan 10,"['Taylor, Neil C.', 'McGouran, Joanna F.']",Front Chem,,,True
2883a8e6fafe65f0dc49b8e2aa1b1f4640f1a8d7,PMC,A Circulating miRNA Signature for Stratification of Breast Lesions among Women with Abnormal Screening Mammograms,http://dx.doi.org/10.3390/cancers11121872,PMC6966622,31769433,CC BY,"Although mammography is the gold standard for breast cancer screening, the high rates of false-positive mammograms remain a concern. Thus, there is an unmet clinical need for a non-invasive and reliable test to differentiate between malignant and benign breast lesions in order to avoid subjecting patients with abnormal mammograms to unnecessary follow-up diagnostic procedures. Serum samples from 116 malignant breast lesions and 64 benign breast lesions were comprehensively profiled for 2,083 microRNAs (miRNAs) using next-generation sequencing. Of the 180 samples profiled, three outliers were removed based on the principal component analysis (PCA), and the remaining samples were divided into training (n = 125) and test (n = 52) sets at a 70:30 ratio for further analysis. In the training set, significantly differentially expressed miRNAs (adjusted p < 0.01) were identified after correcting for multiple testing using a false discovery rate. Subsequently, a predictive classification model using an eight-miRNA signature and a Bayesian logistic regression algorithm was developed. Based on the receiver operating characteristic (ROC) curve analysis in the test set, the model could achieve an area under the curve (AUC) of 0.9542. Together, this study demonstrates the potential use of circulating miRNAs as an adjunct test to stratify breast lesions in patients with abnormal screening mammograms.",2019 Nov 26,"['Loke, Sau Yeen', 'Munusamy, Prabhakaran', 'Koh, Geok Ling', 'Chan, Claire Hian Tzer', 'Madhukumar, Preetha', 'Thung, Jee Liang', 'Tan, Kiat Tee Benita', 'Ong, Kong Wee', 'Yong, Wei Sean', 'Sim, Yirong', 'Oey, Chung Lie', 'Lim, Sue Zann', 'Chan, Mun Yew Patrick', 'Ho, Teng Swan Juliana', 'Khoo, Boon Kheng James', 'Wong, Su Lin Jill', 'Thng, Choon Hua', 'Chong, Bee Kiang', 'Tan, Ern Yu', 'Tan, Veronique Kiak-Mien', 'Lee, Ann Siew Gek']",Cancers (Basel),,,True
bca749d4eb523bb4cb95ac750704bf2b02278964,PMC,A Circulating miRNA Signature for Stratification of Breast Lesions among Women with Abnormal Screening Mammograms,http://dx.doi.org/10.3390/cancers11121872,PMC6966622,31769433,CC BY,"Although mammography is the gold standard for breast cancer screening, the high rates of false-positive mammograms remain a concern. Thus, there is an unmet clinical need for a non-invasive and reliable test to differentiate between malignant and benign breast lesions in order to avoid subjecting patients with abnormal mammograms to unnecessary follow-up diagnostic procedures. Serum samples from 116 malignant breast lesions and 64 benign breast lesions were comprehensively profiled for 2,083 microRNAs (miRNAs) using next-generation sequencing. Of the 180 samples profiled, three outliers were removed based on the principal component analysis (PCA), and the remaining samples were divided into training (n = 125) and test (n = 52) sets at a 70:30 ratio for further analysis. In the training set, significantly differentially expressed miRNAs (adjusted p < 0.01) were identified after correcting for multiple testing using a false discovery rate. Subsequently, a predictive classification model using an eight-miRNA signature and a Bayesian logistic regression algorithm was developed. Based on the receiver operating characteristic (ROC) curve analysis in the test set, the model could achieve an area under the curve (AUC) of 0.9542. Together, this study demonstrates the potential use of circulating miRNAs as an adjunct test to stratify breast lesions in patients with abnormal screening mammograms.",2019 Nov 26,"['Loke, Sau Yeen', 'Munusamy, Prabhakaran', 'Koh, Geok Ling', 'Chan, Claire Hian Tzer', 'Madhukumar, Preetha', 'Thung, Jee Liang', 'Tan, Kiat Tee Benita', 'Ong, Kong Wee', 'Yong, Wei Sean', 'Sim, Yirong', 'Oey, Chung Lie', 'Lim, Sue Zann', 'Chan, Mun Yew Patrick', 'Ho, Teng Swan Juliana', 'Khoo, Boon Kheng James', 'Wong, Su Lin Jill', 'Thng, Choon Hua', 'Chong, Bee Kiang', 'Tan, Ern Yu', 'Tan, Veronique Kiak-Mien', 'Lee, Ann Siew Gek']",Cancers (Basel),,,False
f0f89b444071b6fa4be64b86e5d70a4cab8cb492,PMC,Longitudinal analysis of the antibody repertoire of a Zika virus-infected patient revealed dynamic changes in antibody response,http://dx.doi.org/10.1080/22221751.2019.1701953,PMC6968589,31906823,CC BY,"The Zika virus (ZIKV) is a mosquito-borne flavivirus that causes neonatal abnormalities and other disorders. Antibodies to the ZIKV envelope (E) protein can block infection. In this study, next-generation sequencing (NGS) of immunoglobulin heavy chain (IgH) mRNA transcripts was combined with single-cell PCR cloning of E-binding monoclonal antibodies for analysing antibody response in a patient from the early stages of infection to more than one year after the clearance of the virus. The patient's IgH repertoire 14 and 64 days after symptom onset showed dramatic dominant clonal expansion but low clonal diversity. IgH repertoire 6 months after disease-free status had few dominant clones but increased diversity. E-binding antibodies appeared abundantly in the repertoire during the early stages of infection but quickly declined after clearance of the virus. Certain VH genes such as VH5-10-1 and VH4-39 appeared to be preferentially enlisted for a rapid antibody response to ZIKV infection. Most of these antibodies require relatively few somatic hypermutations to acquire the ability to bind to the E protein, pointing to a possible mechanism for rapid defence against ZIKV infection. This study provides a unique and holistic view of the dynamic changes and characteristics of the antibody response to ZIKV infection.",2020 Jan 6,"['Niu, Xuefeng', 'Yan, Qihong', 'Yao, Zhipeng', 'Zhang, Fan', 'Qu, Linbing', 'Wang, Chunlin', 'Wang, Chengrui', 'Lei, Hui', 'Chen, Chaoming', 'Liang, Renshan', 'Luo, Jia', 'Wang, Qian', 'Zhao, Lingzhai', 'Zhang, Yudi', 'Luo, Kun', 'Wang, Longyu', 'Wu, Hongkai', 'Liu, Tingting', 'Li, Pingchao', 'Zheng, Zhiqiang', 'Tan, Yee Joo', 'Feng, Liqiang', 'Zhang, Zhenhai', 'Han, Jian', 'Zhang, Fuchun', 'Chen, Ling']",Emerg Microbes Infect,,,True
3cf41b596058f2d1b07760563aa6c5316b014af2,PMC,Genetic manipulation of porcine deltacoronavirus reveals insights into NS6 and NS7 functions: a novel strategy for vaccine design,http://dx.doi.org/10.1080/22221751.2019.1701391,PMC6968670,31859605,CC BY,"Porcine deltacoronavirus (PDCoV) is an emerging swine coronavirus that causes severe diarrhea, resulting in high mortality in neonatal piglets. Despite widespread outbreaks in many countries, no effective PDCoV vaccines are currently available. Here, we generated, for the first time, a full-length infectious cDNA clone of PDCoV. We further manipulated the infectious clone by replacing the NS6 gene with a green fluorescent protein (GFP) to generate rPDCoV-ΔNS6-GFP; likewise, rPDCoV-ΔNS7 was constructed by removing the ATG start codons of the NS7 gene. Growth kinetics studies suggest that rPDCoV-ΔNS7 could replicate similarly to that of the wild-type PDCoV, whereas rPDCoV-ΔNS6-GFP exhibited a substantial reduction of viral titer in vitro and in vivo. Piglets inoculated with rPDCoV-ΔNS7 or wild-type PDCoV showed similar diarrheic scores and pathological injury. In contrast, rPDCoV-ΔNS6-GFP-infected piglets did not show any clinical signs, indicating that the NS6 protein is an important virulence factor of PDCoV and that the NS6-deficient mutant virus might be a promising live-attenuated vaccine candidate. Taken together, the reverse genetics platform described here not only provides more insights into the role of PDCoV accessory proteins in viral replication and pathogenesis, but also allows the development of novel vaccines against PDCoV infection.",2019 Dec 20,"['Zhang, Mengjia', 'Li, Wan', 'Zhou, Peng', 'Liu, Dejian', 'Luo, Rui', 'Jongkaewwattana, Anan', 'He, Qigai']",Emerg Microbes Infect,,,True
3ce03de615e79f44ac9d8193429f9f6be86be3a5,PMC,Validation of the easyscreen flavivirus dengue alphavirus detection kit based on 3base amplification technology and its application to the 2016/17 Vanuatu dengue outbreak,http://dx.doi.org/10.1371/journal.pone.0227550,PMC6968865,31951602,CC BY,"BACKGROUND: The family flaviviridae and alphaviridae contain a diverse group of pathogens that cause significant morbidity and mortality worldwide. Diagnosis of the virus responsible for disease is essential to ensure patients receive appropriate clinical management. Very few real-time RT-PCR based assays are able to detect the presence of all members of these families using a single primer and probe set. We have developed a novel chemistry, 3base, which simplifies the viral nucleic acids allowing the design of RT-PCR assays capable of pan-family identification. METHODOLOGY/PRINCIPAL FINDING: Synthetic constructs, viral nucleic acids, intact viral particles and characterised reference materials were used to determine the specificity and sensitivity of the assays. Synthetic constructs demonstrated the sensitivities of the pan-flavivirus detection component were in the range of 13 copies per PCR. The pan-alphavirus assay had a sensitivity range of 10–25 copies per reaction depending on the viral strain. Lower limit of detection studies using whole virus particles demonstrated that sensitivity for assays was in the range of 1–2 copies per reaction. No cross reactivity was observed with a number of commonly encountered viral strains. Proficiency panels showed 100% concordance with the expected results and the assays performed as well as, if not better than, other assays used in laboratories worldwide. After initial assay validation the pan-viral assays were then tested during the 2016–2017 Vanuatu dengue-2 outbreak. Positive results were detected in 116 positives from a total of 187 suspected dengue samples. CONCLUSIONS/SIGNIFICANCE: The pan-viral screening assays described here utilise a novel 3base technology and are shown to provide a sensitive and specific method to screen and thereafter speciate flavi- and/or alpha- viruses in clinical samples. The assays performed well in an outbreak situation and can be used to detect positive clinical samples containing any flavivirus or alphavirus in approximately 3 hours 30 minutes.",2020 Jan 17,"['Garae, Crystal', 'Kalo, Kalkoa', 'Pakoa, George Junior', 'Baker, Rohan', 'Isaacs, Phill', 'Millar, Douglas Spencer']",PLoS One,,,True
d8d17ed0a635b0771ab27b88b15e868759b1dfb2,PMC,Investigations into the presence of nidoviruses in pythons,http://dx.doi.org/10.1186/s12985-020-1279-5,PMC6969405,31952524,CC BY,"BACKGROUND: Pneumonia and stomatitis represent severe and often fatal diseases in different captive snakes. Apart from bacterial infections, paramyxo-, adeno-, reo- and arenaviruses cause these diseases. In 2014, new viruses emerged as the cause of pneumonia in pythons. In a few publications, nidoviruses have been reported in association with pneumonia in ball pythons and a tiger python. The viruses were found using new sequencing methods from the organ tissue of dead animals. METHODS: Severe pneumonia and stomatitis resulted in a high mortality rate in a captive breeding collection of green tree pythons. Unbiased deep sequencing lead to the detection of nidoviral sequences. A developed RT-qPCR was used to confirm the metagenome results and to determine the importance of this virus. A total of 1554 different boid snakes, including animals suffering from respiratory diseases as well as healthy controls, were screened for nidoviruses. Furthermore, in addition to two full-length sequences, partial sequences were generated from different snake species. RESULTS: The assembled full-length snake nidovirus genomes share only an overall genome sequence identity of less than 66.9% to other published snake nidoviruses and new partial sequences vary between 99.89 and 79.4%. Highest viral loads were detected in lung samples. The snake nidovirus was not only present in diseased animals, but also in snakes showing no typical clinical signs. CONCLUSIONS: Our findings further highlight the possible importance of snake nidoviruses in respiratory diseases and proof multiple circulating strains with varying disease potential. Nidovirus detection in clinical healthy individuals might represent testing during the incubation period or reconvalescence. Our investigations show new aspects of nidovirus infections in pythons. Nidoviruses should be included in routine diagnostic workup of diseased reptiles.",2020 Jan 17,"['Blahak, Silvia', 'Jenckel, Maria', 'Höper, Dirk', 'Beer, Martin', 'Hoffmann, Bernd', 'Schlottau, Kore']",Virol J,,,True
faac6cddc8f0126d5f93e948689eead41f54ad1f,PMC,Tonsillar hypertrophy and prolapse in a child – is epiglottitis a predisposing factor for sudden unexpected death?,http://dx.doi.org/10.1186/s12887-020-1927-3,PMC6970282,31959132,CC BY,"BACKGROUND: Tonsillitis, with associated tonsillar hypertrophy, is a common disease of childhood, yet it is rarely associated with sudden death due to airway obstruction. Lethal complications involving the inflamed tonsils include haemorrhage, retropharyngeal abscess and disseminated sepsis. CASE PRESENTATION: We report on a case of sudden and unexpected death in an 8-year-old female who was diagnosed with and treated for tonsillitis. The child was diagnosed with acute tonsillitis 2 days prior to her collapse and was placed on a course of oral antibiotics. There were no signs of upper or lower airway obstruction. She was found to be unresponsive by her caregiver and gasping for air in her bed in the early hours of the second morning after the start of treatment. Autopsy showed massive and symmetrically enlarged palatine tonsils. The tonsils filled the pharynx almost completely. The epiglottis and laryngeal mucosa at the base of the epiglottis in the vicinity of the aryepiglottic membrane and the superior aspect of the larynx displayed red-purple discoloration, with mucosal swelling and edema. Histological examination of the palatine tonsils revealed prominent lymphoid hyperplasia, but no evidence of acute inflammation. CONCLUSION: Palatine tonsillar hypertrophy in infants is a common feature of both viral and bacterial tonsillitis and has been postulated as a possible risk factor for Sudden and Unexplained Death in Infancy (SUDI), based on the theory of mechanical impediment of breathing by narrowing of the upper airway. The rounded shape of the tonsils may facilitate some airflow past the enlarged structures and hence protect against asphyxial death when the enlarged tonsils fill the laryngo-pharynx. Epiglottal and proximal laryngeal edema may play a more significant role in asphyxial unexpected deaths in cases of tonsillitis with tonsillar hypertrophy than previously suspected. This focusses the importance of careful examination of the epiglottis and proximal laryngeal mucosa, as part of a thorough examination of the laryngo-pharynx in cases of sudden death associated with tonsillar hypertrophy.",2020 Jan 20,"['Nieuwoudt, I.', 'Goussard, P.', 'Verster, J.', 'Dempers, J.']",BMC Pediatr,,,True
6091444b4f7495b1b4cb0c72b6f30da73ccf867d,PMC,The human coronavirus HCoV-229E S-protein structure and receptor binding,http://dx.doi.org/10.7554/eLife.51230,PMC6970540,31650956,CC BY,"The coronavirus S-protein mediates receptor binding and fusion of the viral and host cell membranes. In HCoV-229E, its receptor binding domain (RBD) shows extensive sequence variation but how S-protein function is maintained is not understood. Reported are the X-ray crystal structures of Class III-V RBDs in complex with human aminopeptidase N (hAPN), as well as the electron cryomicroscopy structure of the 229E S-protein. The structures show that common core interactions define the specificity for hAPN and that the peripheral RBD sequence variation is accommodated by loop plasticity. The results provide insight into immune evasion and the cross-species transmission of 229E and related coronaviruses. We also find that the 229E S-protein can expose a portion of its helical core to solvent. This is undoubtedly facilitated by hydrophilic subunit interfaces that we show are conserved among coronaviruses. These interfaces likely play a role in the S-protein conformational changes associated with membrane fusion.",,"['Li, Zhijie', 'Tomlinson, Aidan CA', 'Wong, Alan HM', 'Zhou, Dongxia', 'Desforges, Marc', 'Talbot, Pierre J', 'Benlekbir, Samir', 'Rubinstein, John L', 'Rini, James M']",eLife.; 8:e51230,,,True
486ad1536fb8f8a3ac0f4a38ee97fc8af2435cc0,PMC,Transmissible gastroenteritis virus targets Paneth cells to inhibit the self-renewal and differentiation of Lgr5 intestinal stem cells via Notch signaling,http://dx.doi.org/10.1038/s41419-020-2233-6,PMC6971083,31959773,CC BY,"Infection with transmissible gastroenteritis virus (TGEV) has been associated with villous atrophy within 48 h, which seriously disrupts intestinal homeostasis. However, the underlying mechanisms remain elusive. In this study, we found that TGEV infection severely disrupted intestinal homeostasis via inhibition of self-renewal and differentiation in Lgr5 intestinal stem cells (ISCs). Profoundly, TGEV-encoded NSP10/NSP16 protein complex-mediated the inactivation of Notch signaling provided a mechanistic explanation for this phenomenon. Initial invasions by TGEV-targeted Paneth cells through aminopeptidase N (APN) receptor, then inducing mitochondrial damage and ROS generation in them, ultimately causing Paneth cell decrease and loss of Notch factors (DII4 and Hes5), which are essential for Lgr5 ISCs self-renewal and differentiation. Interestingly, loss of Notch signaling induced goblet cells differentiation at the cost of absorptive enterocytes and promoted mucins secretion, which accelerated TGEV replication. Therefore, the more differentiation of goblet cells, the greater TGEV infection in jejunum. These results provide a detailed mechanistic pathway by which villous atrophy sharply occurs in TGEV-infected jejunum within 48 h. Thus, the pathogenesis of TGEV can be described as a “bottom up scenario”, which is contrary to the traditional “top down” hypothesis. Together, our findings provide a potential link between diarrheal virus infection and crypt cells response that regulates Paneth cells function and Lgr5 ISCs fate and could be exploited for therapeutic application.",2020 Jan 20,"['Wu, Aimin', 'Yu, Bing', 'Zhang, Keying', 'Xu, Zhiwen', 'Wu, De', 'He, Jun', 'Luo, Junqiu', 'Luo, Yuheng', 'Yu, Jie', 'Zheng, Ping', 'Che, Lianqiang', 'Mao, Xiangbing', 'Huang, Zhiqing', 'Wang, Lan', 'Zhao, Jun', 'Chen, Daiwen']",Cell Death Dis,,,True
efcc12819b414659eff848729482b1a3958d10cd,PMC,A self-aggregating peptide: implications for the development of thermostable vaccine candidates,http://dx.doi.org/10.1186/s12896-019-0592-9,PMC6971912,31959159,CC BY,"BACKGROUND: The use of biomaterials has been expanded to improve the characteristics of vaccines. Recently we have identified that the peptide PH((1–110)) from polyhedrin self-aggregates and incorporates foreign proteins to form particles. We have proposed that this peptide can be used as an antigen carrying system for vaccines. However, the immune response generated by the antigen fused to the peptide has not been fully characterized. In addition, the adjuvant effect and thermostability of the particles has not been evaluated. RESULTS: In the present study we demonstrate the use of a system developed to generate nano and microparticles carrying as a fusion protein peptides or proteins of interest to be used as vaccines. These particles are purified easily by centrifugation. Immunization of animals with the particles in the absence of adjuvant result in a robust and long-lasting immune response. Proteins contained inside the particles are maintained for over 1 year at ambient temperature, preserving their immunological properties. CONCLUSION: The rapid and efficient production of the particles in addition to the robust immune response they generate position this system as an excellent method for the rapid response against emerging diseases. The thermostability conferred by the particle system facilitates the distribution of the vaccines in developing countries or areas with no electricity.",2020 Jan 21,"['Cruz-Reséndiz, Adolfo', 'Zepeda-Cervantes, Jesús', 'Sampieri, Alicia', 'Bastián-Eugenio, Carlos', 'Acero, Gonzalo', 'Sánchez-Betancourt, J. Iván', 'Gevorkian, Goar', 'Vaca, Luis']",BMC Biotechnol,,,False
9686412e86273bfd8744496f910f0cbed499e701,PMC,A self-aggregating peptide: implications for the development of thermostable vaccine candidates,http://dx.doi.org/10.1186/s12896-019-0592-9,PMC6971912,31959159,CC BY,"BACKGROUND: The use of biomaterials has been expanded to improve the characteristics of vaccines. Recently we have identified that the peptide PH((1–110)) from polyhedrin self-aggregates and incorporates foreign proteins to form particles. We have proposed that this peptide can be used as an antigen carrying system for vaccines. However, the immune response generated by the antigen fused to the peptide has not been fully characterized. In addition, the adjuvant effect and thermostability of the particles has not been evaluated. RESULTS: In the present study we demonstrate the use of a system developed to generate nano and microparticles carrying as a fusion protein peptides or proteins of interest to be used as vaccines. These particles are purified easily by centrifugation. Immunization of animals with the particles in the absence of adjuvant result in a robust and long-lasting immune response. Proteins contained inside the particles are maintained for over 1 year at ambient temperature, preserving their immunological properties. CONCLUSION: The rapid and efficient production of the particles in addition to the robust immune response they generate position this system as an excellent method for the rapid response against emerging diseases. The thermostability conferred by the particle system facilitates the distribution of the vaccines in developing countries or areas with no electricity.",2020 Jan 21,"['Cruz-Reséndiz, Adolfo', 'Zepeda-Cervantes, Jesús', 'Sampieri, Alicia', 'Bastián-Eugenio, Carlos', 'Acero, Gonzalo', 'Sánchez-Betancourt, J. Iván', 'Gevorkian, Goar', 'Vaca, Luis']",BMC Biotechnol,,,False
8345ee4320bbcf9be8ca2847f71fc7f05e45525a,PMC,A self-aggregating peptide: implications for the development of thermostable vaccine candidates,http://dx.doi.org/10.1186/s12896-019-0592-9,PMC6971912,31959159,CC BY,"BACKGROUND: The use of biomaterials has been expanded to improve the characteristics of vaccines. Recently we have identified that the peptide PH((1–110)) from polyhedrin self-aggregates and incorporates foreign proteins to form particles. We have proposed that this peptide can be used as an antigen carrying system for vaccines. However, the immune response generated by the antigen fused to the peptide has not been fully characterized. In addition, the adjuvant effect and thermostability of the particles has not been evaluated. RESULTS: In the present study we demonstrate the use of a system developed to generate nano and microparticles carrying as a fusion protein peptides or proteins of interest to be used as vaccines. These particles are purified easily by centrifugation. Immunization of animals with the particles in the absence of adjuvant result in a robust and long-lasting immune response. Proteins contained inside the particles are maintained for over 1 year at ambient temperature, preserving their immunological properties. CONCLUSION: The rapid and efficient production of the particles in addition to the robust immune response they generate position this system as an excellent method for the rapid response against emerging diseases. The thermostability conferred by the particle system facilitates the distribution of the vaccines in developing countries or areas with no electricity.",2020 Jan 21,"['Cruz-Reséndiz, Adolfo', 'Zepeda-Cervantes, Jesús', 'Sampieri, Alicia', 'Bastián-Eugenio, Carlos', 'Acero, Gonzalo', 'Sánchez-Betancourt, J. Iván', 'Gevorkian, Goar', 'Vaca, Luis']",BMC Biotechnol,,,False
2944d68620dca1f4b8786fd684d4481db920a646,PMC,A self-aggregating peptide: implications for the development of thermostable vaccine candidates,http://dx.doi.org/10.1186/s12896-019-0592-9,PMC6971912,31959159,CC BY,"BACKGROUND: The use of biomaterials has been expanded to improve the characteristics of vaccines. Recently we have identified that the peptide PH((1–110)) from polyhedrin self-aggregates and incorporates foreign proteins to form particles. We have proposed that this peptide can be used as an antigen carrying system for vaccines. However, the immune response generated by the antigen fused to the peptide has not been fully characterized. In addition, the adjuvant effect and thermostability of the particles has not been evaluated. RESULTS: In the present study we demonstrate the use of a system developed to generate nano and microparticles carrying as a fusion protein peptides or proteins of interest to be used as vaccines. These particles are purified easily by centrifugation. Immunization of animals with the particles in the absence of adjuvant result in a robust and long-lasting immune response. Proteins contained inside the particles are maintained for over 1 year at ambient temperature, preserving their immunological properties. CONCLUSION: The rapid and efficient production of the particles in addition to the robust immune response they generate position this system as an excellent method for the rapid response against emerging diseases. The thermostability conferred by the particle system facilitates the distribution of the vaccines in developing countries or areas with no electricity.",2020 Jan 21,"['Cruz-Reséndiz, Adolfo', 'Zepeda-Cervantes, Jesús', 'Sampieri, Alicia', 'Bastián-Eugenio, Carlos', 'Acero, Gonzalo', 'Sánchez-Betancourt, J. Iván', 'Gevorkian, Goar', 'Vaca, Luis']",BMC Biotechnol,,,False
c31bc0c789d1d20a5fcdc865f73f01ed4d75bfc7,PMC,A self-aggregating peptide: implications for the development of thermostable vaccine candidates,http://dx.doi.org/10.1186/s12896-019-0592-9,PMC6971912,31959159,CC BY,"BACKGROUND: The use of biomaterials has been expanded to improve the characteristics of vaccines. Recently we have identified that the peptide PH((1–110)) from polyhedrin self-aggregates and incorporates foreign proteins to form particles. We have proposed that this peptide can be used as an antigen carrying system for vaccines. However, the immune response generated by the antigen fused to the peptide has not been fully characterized. In addition, the adjuvant effect and thermostability of the particles has not been evaluated. RESULTS: In the present study we demonstrate the use of a system developed to generate nano and microparticles carrying as a fusion protein peptides or proteins of interest to be used as vaccines. These particles are purified easily by centrifugation. Immunization of animals with the particles in the absence of adjuvant result in a robust and long-lasting immune response. Proteins contained inside the particles are maintained for over 1 year at ambient temperature, preserving their immunological properties. CONCLUSION: The rapid and efficient production of the particles in addition to the robust immune response they generate position this system as an excellent method for the rapid response against emerging diseases. The thermostability conferred by the particle system facilitates the distribution of the vaccines in developing countries or areas with no electricity.",2020 Jan 21,"['Cruz-Reséndiz, Adolfo', 'Zepeda-Cervantes, Jesús', 'Sampieri, Alicia', 'Bastián-Eugenio, Carlos', 'Acero, Gonzalo', 'Sánchez-Betancourt, J. Iván', 'Gevorkian, Goar', 'Vaca, Luis']",BMC Biotechnol,,,False
e1f2c0859f44eaf3e7a2110a5ca98ac0104815bc,PMC,A self-aggregating peptide: implications for the development of thermostable vaccine candidates,http://dx.doi.org/10.1186/s12896-019-0592-9,PMC6971912,31959159,CC BY,"BACKGROUND: The use of biomaterials has been expanded to improve the characteristics of vaccines. Recently we have identified that the peptide PH((1–110)) from polyhedrin self-aggregates and incorporates foreign proteins to form particles. We have proposed that this peptide can be used as an antigen carrying system for vaccines. However, the immune response generated by the antigen fused to the peptide has not been fully characterized. In addition, the adjuvant effect and thermostability of the particles has not been evaluated. RESULTS: In the present study we demonstrate the use of a system developed to generate nano and microparticles carrying as a fusion protein peptides or proteins of interest to be used as vaccines. These particles are purified easily by centrifugation. Immunization of animals with the particles in the absence of adjuvant result in a robust and long-lasting immune response. Proteins contained inside the particles are maintained for over 1 year at ambient temperature, preserving their immunological properties. CONCLUSION: The rapid and efficient production of the particles in addition to the robust immune response they generate position this system as an excellent method for the rapid response against emerging diseases. The thermostability conferred by the particle system facilitates the distribution of the vaccines in developing countries or areas with no electricity.",2020 Jan 21,"['Cruz-Reséndiz, Adolfo', 'Zepeda-Cervantes, Jesús', 'Sampieri, Alicia', 'Bastián-Eugenio, Carlos', 'Acero, Gonzalo', 'Sánchez-Betancourt, J. Iván', 'Gevorkian, Goar', 'Vaca, Luis']",BMC Biotechnol,,,True
c7c6c6ff7580f79ffba12017575ac3ccca4bc9b7,PMC,Endoplasmic reticulum: a focal point of Zika virus infection,http://dx.doi.org/10.1186/s12929-020-0618-6,PMC6971992,31959174,CC BY,"Zika virus (ZIKV) belongs to the Flavivirus genus of the Flaviviridae family. It is an arbovirus that can cause congenital abnormalities and is sexually transmissible. A series of outbreaks accompanied by unexpected severe clinical complications have captured medical attention to further characterize the clinical features of congenital ZIKV syndrome and its underlying pathophysiological mechanisms. Endoplasmic reticulum (ER) and ER-related proteins are essential in ZIKV genome replication. This review highlights the subcellular localization of ZIKV to the ER and ZIKV modulation on the architecture of the ER. This review also discusses ZIKV interaction with ER proteins such as signal peptidase complex subunit 1 (SPCS1), ER membrane complex (EMC) subunits, and ER translocon for viral replication. Furthermore, the review covers several important resulting effects of ZIKV infection to the ER and cellular processes including ER stress, reticulophagy, and paraptosis-like death. Pharmacological targeting of ZIKV-affected ER-resident proteins and ER-associated components demonstrate promising signs of combating ZIKV infection and rescuing host organisms from severe neurologic sequelae.",2020 Jan 20,"['Mohd Ropidi, Muhammad Izzuddin', 'Khazali, Ahmad Suhail', 'Nor Rashid, Nurshamimi', 'Yusof, Rohana']",J Biomed Sci,,,True
881739c1040a5d2fa7024857e21aec68e4d25230,PMC,Ebola in the Eastern Democratic Republic of Congo: One Health approach to infectious disease control,http://dx.doi.org/10.1016/j.onehlt.2019.100117,PMC6976930,31993475,CC BY,"The Democratic Republic of Congo (DRC) is facing its tenth outbreak of Ebola virus disease (EVD), in North-Kivu and Ituri provinces. This is the second most deadly EVD outbreak in history, after the one that occurred in West Africa in 2014. The DRC Ministry of Health (MoH), supported by the World Health Organization (WHO) and a range of regional and international partners, are implementing EVD response plans in these affected areas such as screening of suspect cases at points of entry, case detection, contact tracing, laboratory testing, case management and infection prevention and control, safe and dignified burials, ring vaccination (this involves vaccination of infected individuals, direct contacts of infected individuals and contacts of their contacts), and therapeutics, community mobilization and free access to healthcare services. Despite these efforts, there has been a sharp rise in the number of confirmed cases within the identified affected areas, and due to a number of challenges unique to DRC, there has been an expansion in the geographical extent of transmission. The significance of the proximity of these regions to wildlife and the Virunga National Park is questionable in the EVD transmission dynamics. The close interaction between human, animal, and environmental factors, in combination with high population movement due to regular rebel attacks in these regions, suggest the need for the integration of the One Health approach in the holistic response plans for control and prevention of EVD. This paper seeks to highlight the implications and importance of a One Health–based approach into the infectious diseases control program implementation in DRC.",2019 Dec 5,"['Sikakulya, Franck katembo', 'Mulisya, Olivier', 'Munyambalu, Dalton Kambale', 'Bunduki, Gabriel Kambale']",One Health,,,False
036bbd8c099c5721274abb4067872f2a68b6193a,PMC,Middle East Respiratory Syndrome Coronavirus Antibodies in Bactrian and Hybrid Camels from Dubai,http://dx.doi.org/10.1128/mSphere.00898-19,PMC6977179,31969478,CC BY,"So far, dromedary camels are the only known animal reservoir for Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV). Previous published serological studies showed that sera of Bactrian camels were all negative for MERS-CoV antibodies. However, a recent study revealed that direct inoculation of Bactrian camels intranasally with MERS-CoV can lead to infection with abundant virus shedding and seroconversion. In this study, we examined the presence of MERS-CoV antibodies in Bactrian and hybrid camels in Dubai, the United Arab Emirates (where dromedaries are also present), and Bactrian camels in Xinjiang, China (where dromedaries are absent). For the 29 serum samples from Bactrian camels in Dubai tested by the MERS-CoV spike (S) protein-based enzyme-linked immunosorbent assay (S-ELISA) and neutralization antibody test, 14 (48%) and 12 (41%), respectively, were positive for MERS-CoV antibodies. All the 12 serum samples that were positive with the neutralization antibody test were also positive for the S-ELISA. For the 11 sera from hybrid camels in Dubai tested with the S-ELISA and neutralization antibody test, 6 (55%) and 9 (82%), respectively, were positive for MERS-CoV antibodies. All the 6 serum samples that were positive for the S-ELISA were also positive with the neutralization antibody test. There was a strong correlation between the antibody levels detected by S-ELISA and neutralizing antibody titers, with a Spearman coefficient of 0.6262 (P < 0.0001; 95% confidence interval, 0.5062 to 0.7225). All 92 Bactrian camel serum samples from Xinjiang were negative for MERS-CoV antibodies tested using both S-ELISA and the neutralization antibody test. Bactrian and hybrid camels are potential sources of MERS-CoV infection. IMPORTANCE Since its first appearance in 2012, Middle East respiratory syndrome (MERS) has affected >25 countries, with >2,400 cases and an extremely high fatality rate of >30%. The total number of mortalities due to MERS is already greater than that due to severe acute respiratory syndrome. MERS coronavirus (MERS-CoV) has been confirmed to be the etiological agent. So far, dromedaries are the only known animal reservoir for MERS-CoV. Previously published serological studies showed that sera of Bactrian camels were all negative for MERS-CoV antibodies. In this study, we observed that 41% of the Bactrian camel sera and 55% of the hybrid camel sera from Dubai (where dromedaries are also present), but none of the sera from Bactrian camels in Xinjiang (where dromedaries are absent), were positive for MERS-CoV antibodies. Based on these results, we conclude that in addition to dromedaries, Bactrian and hybrid camels are also potential sources of MERS-CoV infection.",2020 Jan 22,"['Lau, Susanna K. P.', 'Li, Kenneth S. M.', 'Luk, Hayes K. H.', 'He, Zirong', 'Teng, Jade L. L.', 'Yuen, Kwok-Yung', 'Wernery, Ulrich', 'Woo, Patrick C. Y.']",mSphere,,,True
5349f364152c9a5e133f282cf5a1bd2449f8930b,PMC,Evaluation of a multiplex PCR assay for detection of respiratory viruses and Mycoplasma pneumoniae in oropharyngeal swab samples from outpatients,http://dx.doi.org/10.1002/jcla.23032,PMC6977335,31628684,CC BY,"BACKGROUND: Respiratory viruses, such as influenza viruses, initially infect the upper airways but can manifest as severe lower respiratory tract infections in high‐risk patients with significant morbidity and mortality. For syndromic diagnosis, several multiplex nucleic acid amplification tests have been developed for clinics, of which SureX 13 Respiratory Pathogen Multiplex Kit (ResP) can simultaneously detect 13 pathogens directly from airway secretion specimens. The organisms identified are influenza virus A, influenza virus A pdmH1N1 (2009), influenza virus A H3N2, influenza virus B, adenovirus, boca virus, rhinovirus, parainfluenza virus, coronavirus, respiratory syncytial virus, human metapneumovirus, Mycoplasma pneumoniae, and Chlamydia. METHODS: This study provides performance evaluation data of this assay by comparing with pathogen‐specific PCRs from oropharyngeal swab samples. RESULTS: Ten pathogens were detected in this assay, of which rhinovirus, adenovirus, and influenza virus A pdmH1N1 (2009) were the most common. The overall agreement between the ResP and the comparator tests was 93.8%. The ResP demonstrated 86.5% agreement for positive results and 97.8% agreement for negative results. CONCLUSION: The ResP assay demonstrated a highly concordant performance comparing with pathogen‐specific PCRs for detection of respiratory pathogens in oropharyngeal swabs from outpatients and could aid in the diagnosis of respiratory infections in a variety of clinical scenarios.",2019 Oct 19,"['Zhang, Ying', 'Cao, Lan', 'Xu, Zhi', 'Zhu, Pingting', 'Huang, Bing', 'Li, Kuibiao', 'Xu, Yang', 'Zhang, Zhoubin', 'Wu, Yong', 'Di, Biao']",J Clin Lab Anal,,,True
6d002db4a643cb5525e9a3b80954b75973706d6b,PMC,"Willingness to Self-Isolate When Facing a Pandemic Risk: Model, Empirical Test, and Policy Recommendations",http://dx.doi.org/10.3390/ijerph17010197,PMC6981847,31892171,CC BY,"Infected people are isolated to minimize the spread of pandemic diseases. Therefore, the factors related to self-isolation (SI) should not be neglected, and it is important to investigate the factors leading the infected (or possibly infected) people to choose to self-isolate. In this paper, we tried to show that the theory of planned behavior provides a useful conceptual framework for SI when facing a pandemic risk, and a regression method with Chinese provincial (Guangdong Province) data was applied to investigate how attitude (ATT), subjective norms (SN), and perceived behavioral control (PBC) influence SI when facing a pandemic emergency. The results and the robustness tests confirm that ATT, SN, and PBC have a significant positive influence on SI when facing a pandemic emergency. ATT plays the most important role, followed by SN and then PBC. Based on the factors of SI, we found, through theoretical and empirical analyses, at least three important aspects that local governments need to consider to encourage citizens to self-isolate when facing a pandemic.",2020 Jan 27,"['Zhang, Xiaojun', 'Wang, Fanfan', 'Zhu, Changwen', 'Wang, Zhiqiang']",Int J Environ Res Public Health,,,True
7df37eb3cc184f38b1d97fe12f7176b5da78f77f,PMC,Effect of Information Disclosure Policy on Control of Infectious Disease: MERS-CoV Outbreak in South Korea,http://dx.doi.org/10.3390/ijerph17010305,PMC6981968,31906369,CC BY,"This study examined the effect of disclosing a list of hospitals with Middle East respiratory syndrome coronavirus (MERS-CoV) patients on the number of laboratory-confirmed MERS-CoV cases in South Korea. MERS-CoV data from 20 May 2015 to 5 July 2015 were from the Korean Ministry of Health & Welfare website and analyzed using segmented linear autoregressive error models for interrupted time series. This study showed that the number of laboratory-confirmed cases was increased by 9.632 on 5 June (p < 0.001). However, this number was significantly decreased following disclosure of a list of hospitals with MERS-CoV cases (Estimate = −0.699; p < 0.001). Disclosing the list of hospitals exposed to MERS-CoV was critical to the prevention of further infection. It reduced the number of confirmed MERS-CoV cases. Thus, providing accurate and timely information is a key to critical care response.",2020 Jan 1,"['Noh, Jin-Won', 'Yoo, Ki-Bong', 'Kwon, Young Dae', 'Hong, Jin Hyuk', 'Lee, Yejin', 'Park, Kisoo']",Int J Environ Res Public Health,,,True
3c7d045c73a10e8b81cc58d86d7cf5d144f83b1b,PMC,Mechanistic Insight of Na/K-ATPase Signaling and HO-1 into Models of Obesity and Nonalcoholic Steatohepatitis,http://dx.doi.org/10.3390/ijms21010087,PMC6982200,31877680,CC BY,"Obesity is a multifaceted pathophysiological condition that has been associated with lipid accumulation, adipocyte dysfunction, impaired mitochondrial biogenesis and an altered metabolic profile. Redox imbalance and excessive release of inflammatory mediators have been intricately linked in obesity-associated phenotypes. Hence, understanding the mechanisms of redox signaling pathways and molecular targets exacerbating oxidative stress is crucial in improving health outcomes. The activation of Na/K-ATPase/Src signaling, and its downstream pathways, by reactive oxygen species (ROS) has been recently implicated in obesity and subsequent nonalcoholic steatohepatitis (NASH), which causes further production of ROS creating an oxidant amplification loop. Apart from that, numerous studies have also characterized antioxidant properties of heme oxygenase 1 (HO-1), which is suppressed in an obese state. The induction of HO-1 restores cellular redox processes, which contributes to inhibition of the toxic milieu. The novelty of these independent mechanisms presents a unique opportunity to unravel their potential as molecular targets for redox regulation in obesity and NASH. The attenuation of oxidative stress, by understanding the underlying molecular mechanisms and associated mediators, with a targeted treatment modality may provide for improved therapeutic options to combat clinical disorders.",2019 Dec 21,"['Pratt, Rebecca', 'Lakhani, Hari Vishal', 'Zehra, Mishghan', 'Desauguste, Rutmann', 'Pillai, Sneha S.', 'Sodhi, Komal']",Int J Mol Sci,,,True
fadd90c71b61efc6c47a0117d160ca9c77a914ec,PMC,A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs,http://dx.doi.org/10.3390/ijms21010302,PMC6982300,31906285,CC BY,"In late 2012 it was evidenced that most of the human genome is transcribed but only a small percentage of the transcripts are translated. This observation supported the importance of non-coding RNAs and it was confirmed in several organisms. The most abundant non-translated transcripts are long non-coding RNAs (lncRNAs). In contrast to protein-coding RNAs, they show a more cell-specific expression. To understand the function of lncRNAs, it is fundamental to investigate in which cells they are preferentially expressed and to detect their subcellular localization. Recent improvements of techniques that localize single RNA molecules in tissues like single-cell RNA sequencing and fluorescence amplification methods have given a considerable boost in the knowledge of the lncRNA functions. In recent years, single-cell transcription variability was associated with non-coding RNA expression, revealing this class of RNAs as important transcripts in the cell lineage specification. The purpose of this review is to collect updated information about lncRNA classification and new findings on their function derived from single-cell analysis. We also retained useful for all researchers to describe the methods available for single-cell analysis and the databases collecting single-cell and lncRNA data. Tables are included to schematize, describe, and compare exposed concepts.",2020 Jan 1,"['Alessio, Enrico', 'Bonadio, Raphael Severino', 'Buson, Lisa', 'Chemello, Francesco', 'Cagnin, Stefano']",Int J Mol Sci,,,True
300738e128112ee5721442ca851bc5769f1a9b64,PMC,Lignans and Their Derivatives from Plants as Antivirals,http://dx.doi.org/10.3390/molecules25010183,PMC6982783,31906391,CC BY,"Lignans are widely produced by various plant species; they are a class of natural products that share structural similarity. They usually contain a core scaffold that is formed by two or more phenylpropanoid units. Lignans possess diverse pharmacological properties, including their antiviral activities that have been reported in recent years. This review discusses the distribution of lignans in nature according to their structural classification, and it provides a comprehensive summary of their antiviral activities. Among them, two types of antiviral lignans—podophyllotoxin and bicyclol, which are used to treat venereal warts and chronic hepatitis B (CHB) in clinical, serve as examples of using lignans for antivirals—are discussed in some detail. Prospects of lignans in antiviral drug discovery are also discussed.",2020 Jan 1,"['Cui, Qinghua', 'Du, Ruikun', 'Liu, Miaomiao', 'Rong, Lijun']",Molecules,,,True
aefeb0e9f2d0db1868113232cdb87597e7614068,PMC,Aptamers Chemistry: Chemical Modifications and Conjugation Strategies,http://dx.doi.org/10.3390/molecules25010003,PMC6982925,31861277,CC BY,"Soon after they were first described in 1990, aptamers were largely recognized as a new class of biological ligands that can rival antibodies in various analytical, diagnostic, and therapeutic applications. Aptamers are short single-stranded RNA or DNA oligonucleotides capable of folding into complex 3D structures, enabling them to bind to a large variety of targets ranging from small ions to an entire organism. Their high binding specificity and affinity make them comparable to antibodies, but they are superior regarding a longer shelf life, simple production and chemical modification, in addition to low toxicity and immunogenicity. In the past three decades, aptamers have been used in a plethora of therapeutics and drug delivery systems that involve innovative delivery mechanisms and carrying various types of drug cargos. However, the successful translation of aptamer research from bench to bedside has been challenged by several limitations that slow down the realization of promising aptamer applications as therapeutics at the clinical level. The main limitations include the susceptibility to degradation by nucleases, fast renal clearance, low thermal stability, and the limited functional group diversity. The solution to overcome such limitations lies in the chemistry of aptamers. The current review will focus on the recent arts of aptamer chemistry that have been evolved to refine the pharmacological properties of aptamers. Moreover, this review will analyze the advantages and disadvantages of such chemical modifications and how they impact the pharmacological properties of aptamers. Finally, this review will summarize the conjugation strategies of aptamers to nanocarriers for developing targeted drug delivery systems.",2019 Dec 18,"['Odeh, Fadwa', 'Nsairat, Hamdi', 'Alshaer, Walhan', 'Ismail, Mohammad A.', 'Esawi, Ezaldeen', 'Qaqish, Baraa', 'Bawab, Abeer Al', 'Ismail, Said I.']",Molecules,,,True
91895a1125e6b20cc3e8439e5a223763b5cb694e,PMC,Prediction of RNA-protein interactions using conjoint triad feature and chaos game representation,http://dx.doi.org/10.1080/21655979.2018.1470721,PMC6984769,30117758,CC BY,"RNA-protein interactions (RPIs) play a very important role in a wide range of post-transcriptional regulations, and identifying whether a given RNA-protein pair can form interactions or not is a vital prerequisite for dissecting the regulatory mechanisms of functional RNAs. Currently, expensive and time-consuming biological assays can only determine a very small portion of all RPIs, which calls for computational approaches to help biologists efficiently and correctly find candidate RPIs. Here, we integrated a successful computing algorithm, conjoint triad feature (CTF), and another method, chaos game representation (CGR), for representing RNA-protein pairs and by doing so developed a prediction model based on these representations and random forest (RF) classifiers. When testing two benchmark datasets, RPI369 and RPI2241, the combined method (CTF+CGR) showed some superiority compared with four existing tools. Especially on RPI2241, the CTF+CGR method improved prediction accuracy (ACC) from 0.91 (the best record of all published works) to 0.95. When independently testing a newly constructed dataset, RPI1449, which only contained experimentally validated RPIs released between 2014 and 2016, our method still showed some generalization capability with an ACC of 0.75. Accordingly, we believe that our hybrid CTF+CGR method will be an important tool for predicting RPIs in the future.",2018 Aug 17,"['Wang, Hongchu', 'Wu, Pengfei']",Bioengineered,,,True
f261de4ce70f551ec9bdc573256bef4a61f43174,PMC,Droplet-Transmitted Infection Risk Ranking Based on Close Proximity Interaction,http://dx.doi.org/10.3389/fnbot.2019.00113,PMC6985151,32038220,CC BY,"We propose an automatic method to identify people who are potentially-infected by droplet-transmitted diseases. This high-risk group of infection was previously identified by conducting large-scale visits/interviews, or manually screening among tons of recorded surveillance videos. Both are time-intensive and most likely to delay the control of communicable diseases like influenza. In this paper, we address this challenge by solving a multi-tasking problem from the captured surveillance videos. This multi-tasking framework aims to model the principle of Close Proximity Interaction and thus infer the infection risk of individuals. The complete workflow includes three essential sub-tasks: (1) person re-identification (REID), to identify the diagnosed patient and infected individuals across different cameras, (2) depth estimation, to provide a spatial knowledge of the captured environment, (3) pose estimation, to evaluate the distance between the diagnosed and potentially-infected subjects. Our method significantly reduces the time and labor costs. We demonstrate the advantages of high accuracy and efficiency of our method. Our method is expected to be effective in accelerating the process of identifying the potentially infected group and ultimately contribute to the well-being of public health.",2020 Jan 21,"['Guo, Shihui', 'Yu, Jubo', 'Shi, Xinyu', 'Wang, Hongran', 'Xie, Feibin', 'Gao, Xing', 'Jiang, Min']",Front Neurorobot,,,True
2522231ac6a1faeccfaf8f71e1bdc7cc81c7c647,PMC,Characterization of Influenza A Virus Infection in Mouse Pulmonary Stem/Progenitor Cells,http://dx.doi.org/10.3389/fmicb.2019.02942,PMC6985155,32038512,CC BY,"The pulmonary stem/progenitor cells, which could be differentiated into downstream cells to repair tissue damage caused by influenza A virus, have also been shown to be the target cells of influenza virus infection. In this study, mouse pulmonary stem/progenitor cells (mPSCs) with capability to differentiate into type I or type II alveolar cells were used as an in vitro cell model to characterize replication and pathogenic effects of influenza viruses in PSCs. First, mPSCs and its immortalized cell line mPSCs(Oct4+) were shown to be susceptible to PR8, seasonal H1N1, 2009 pandemic H1N1, and H7N9 influenza viruses and can generate infectious virus particles, although with a lower virus titer, which could be attributed by the reduced vRNA replication and nucleoprotein (NP) aggregation in the cytoplasm. Nevertheless, a significant increase of interleukin (IL)-6 and interferon (IFN)-γ at 12 h and IFN-β at 24 h post infection in mPSCs implicates that mPSCs might function as a sensor to modulate immune responses to influenza virus infection. In summary, our results demonstrated mPSCs, as one of the target cells for influenza A viruses, could modulate early proinflammatory responses to influenza virus infection.",2020 Jan 21,"['Chao, Tai-Ling', 'Gu, Sing-Yi', 'Lin, Pi-Han', 'Chou, Yu-Tien', 'Ling, Thai-Yen', 'Chang, Sui-Yuan']",Front Microbiol,,,True
b0ece8ef777c5e15e41c4140cb6be2a8944af191,PMC,Strategies to Target ISG15 and USP18 Toward Therapeutic Applications,http://dx.doi.org/10.3389/fchem.2019.00923,PMC6985271,32039148,CC BY,"The interferon (IFN)-stimulated gene product 15 (ISG15) represents an ubiquitin-like protein (Ubl), which in a process termed ISGylation can be covalently linked to target substrates via a cascade of E1, E2, and E3 enzymes. Furthermore, ISG15 exerts functions in its free form both, as an intracellular and as a secreted protein. In agreement with its role as a type I IFN effector, most functions of ISG15 and ISGylation are linked to the anti-pathogenic response. However, also key roles in other cellular processes such as protein translation, cytoskeleton dynamics, exosome secretion, autophagy or genome stability and cancer were described. Ubiquitin-specific protease 18 (USP18) constitutes the major ISG15 specific protease which counteracts ISG15 conjugation. Remarkably, USP18 also functions as a critical negative regulator of the IFN response irrespective of its enzymatic activity. Concordantly, lack of USP18 function causes fatal interferonopathies in humans and mice. The negative regulatory function of USP18 in IFN signaling is regulated by various protein–protein interactions and its stability is controlled via proteasomal degradation. The broad repertoire of physiological functions and regulation of ISG15 and USP18 offers a variety of potential intervention strategies which might be of therapeutic use. Due to the high mutation rates of pathogens which are often species specific and constantly give rise to a variety of immune evasion mechanisms, immune effector systems are under constant evolutionarily pressure. Therefore, it is not surprising that considerable differences in ISG15 with respect to function and sequence exist even among closely related species. Hence, it is essential to thoroughly evaluate the translational potential of results obtained in model organisms especially for therapeutic strategies. This review covers existing and conceptual assay systems to target and identify modulators of ISG15, ISGylation, USP18 function, and protein–protein interactions within this context. Strategies comprise mouse models for translational perspectives, cell-based and biochemical assays as well as chemical probes.",2020 Jan 21,"['Jiménez Fernández, Daniel', 'Hess, Sandra', 'Knobeloch, Klaus-Peter']",Front Chem,,,True
55f72abf2de5e0b70b27e9ed512b9e456407b680,PMC,Analysis of the Potential for N(4)-Hydroxycytidine To Inhibit Mitochondrial Replication and Function,http://dx.doi.org/10.1128/AAC.01719-19,PMC6985706,31767721,CC BY,"N(4)-Hydroxycytidine (NHC) is an antiviral ribonucleoside analog that acts as a competitive alternative substrate for virally encoded RNA-dependent RNA polymerases. It exhibits measurable levels of cytotoxicity, with 50% cytotoxic concentration values ranging from 7.5 μM in CEM cells and up to >100 μM in other cell lines. The mitochondrial DNA-dependent RNA polymerase (POLRMT) has been shown to incorporate some nucleotide analogs into mitochondrial RNAs, resulting in substantial mitochondrial toxicity. NHC was tested in multiple assays intended to determine its potential to cause mitochondrial toxicity. NHC showed similar cytotoxicity in HepG2 cells incubated in a glucose-free and glucose-containing media, suggesting that NHC does not impair mitochondrial function in this cell line based on the Crabtree effect. We demonstrate that the 5′-triphosphate of NHC can be used by POLRMT for incorporation into nascent RNA chain but does not cause immediate chain termination. In PC-3 cells treated with NHC, the 50% inhibitory concentrations of mitochondrial protein expression inhibition were 2.7-fold lower than those for nuclear-encoded protein expression, but this effect did not result in selective mitochondrial toxicity. A 14-day incubation of HepG2 cells with NHC had no effect on mitochondrial DNA copy number or extracellular lactate levels. In CEM cells treated with NHC at 10 μM, a slight decrease (by ∼20%) in mitochondrial DNA copy number and a corresponding slight increase in extracellular lactate levels were detected, but these effects were not enhanced by an increase in NHC treatment concentration. In summary, the results indicate that mitochondrial impairment by NHC is not the main contributor to the compound’s observed cytotoxicity in these cell lines.",2020 Jan 27,"['Sticher, Zachary M.', 'Lu, Gaofei', 'Mitchell, Deborah G.', 'Marlow, Joshua', 'Moellering, Levi', 'Bluemling, Gregory R.', 'Guthrie, David B.', 'Natchus, Michael G.', 'Painter, George R.', 'Kolykhalov, Alexander A.']",Antimicrob Agents Chemother,,,True
bf30ca226d68a47371af20b85605f7c8550d2dd4,PMC,Analysis of the Potential for N(4)-Hydroxycytidine To Inhibit Mitochondrial Replication and Function,http://dx.doi.org/10.1128/AAC.01719-19,PMC6985706,31767721,CC BY,"N(4)-Hydroxycytidine (NHC) is an antiviral ribonucleoside analog that acts as a competitive alternative substrate for virally encoded RNA-dependent RNA polymerases. It exhibits measurable levels of cytotoxicity, with 50% cytotoxic concentration values ranging from 7.5 μM in CEM cells and up to >100 μM in other cell lines. The mitochondrial DNA-dependent RNA polymerase (POLRMT) has been shown to incorporate some nucleotide analogs into mitochondrial RNAs, resulting in substantial mitochondrial toxicity. NHC was tested in multiple assays intended to determine its potential to cause mitochondrial toxicity. NHC showed similar cytotoxicity in HepG2 cells incubated in a glucose-free and glucose-containing media, suggesting that NHC does not impair mitochondrial function in this cell line based on the Crabtree effect. We demonstrate that the 5′-triphosphate of NHC can be used by POLRMT for incorporation into nascent RNA chain but does not cause immediate chain termination. In PC-3 cells treated with NHC, the 50% inhibitory concentrations of mitochondrial protein expression inhibition were 2.7-fold lower than those for nuclear-encoded protein expression, but this effect did not result in selective mitochondrial toxicity. A 14-day incubation of HepG2 cells with NHC had no effect on mitochondrial DNA copy number or extracellular lactate levels. In CEM cells treated with NHC at 10 μM, a slight decrease (by ∼20%) in mitochondrial DNA copy number and a corresponding slight increase in extracellular lactate levels were detected, but these effects were not enhanced by an increase in NHC treatment concentration. In summary, the results indicate that mitochondrial impairment by NHC is not the main contributor to the compound’s observed cytotoxicity in these cell lines.",2020 Jan 27,"['Sticher, Zachary M.', 'Lu, Gaofei', 'Mitchell, Deborah G.', 'Marlow, Joshua', 'Moellering, Levi', 'Bluemling, Gregory R.', 'Guthrie, David B.', 'Natchus, Michael G.', 'Painter, George R.', 'Kolykhalov, Alexander A.']",Antimicrob Agents Chemother,,,True
1f05e1ead21fddf2eda7d8b969bc8c7ecd873be8,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.20.010220,PMC6986229,32015575,CC BY,,2020 Feb 1,,Bull World Health Organ,,,False
55442eff1ea9166574f300753f493d7ac7ca6987,PMC,Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR,http://dx.doi.org/10.2807/1560-7917.ES.2020.25.3.2000045,PMC6988269,31992387,CC BY,"BACKGROUND: The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. AIM: We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. METHODS: Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. RESULTS: The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. CONCLUSION: The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.",2020 Jan 23,"['Corman, Victor M', 'Landt, Olfert', 'Kaiser, Marco', 'Molenkamp, Richard', 'Meijer, Adam', 'Chu, Daniel KW', 'Bleicker, Tobias', 'Brünink, Sebastian', 'Schneider, Julia', 'Schmidt, Marie Luisa', 'Mulders, Daphne GJC', 'Haagmans, Bart L', 'van der Veer, Bas', 'van den Brink, Sharon', 'Wijsman, Lisa', 'Goderski, Gabriel', 'Romette, Jean-Louis', 'Ellis, Joanna', 'Zambon, Maria', 'Peiris, Malik', 'Goossens, Herman', 'Reusken, Chantal', 'Koopmans, Marion PG', 'Drosten, Christian']",Euro Surveill,,,False
ee6e4fcb9272a59d35f6ec53be5a8cff4d8c0b21,PMC,Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR,http://dx.doi.org/10.2807/1560-7917.ES.2020.25.3.2000045,PMC6988269,31992387,CC BY,"BACKGROUND: The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. AIM: We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. METHODS: Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. RESULTS: The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. CONCLUSION: The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.",2020 Jan 23,"['Corman, Victor M', 'Landt, Olfert', 'Kaiser, Marco', 'Molenkamp, Richard', 'Meijer, Adam', 'Chu, Daniel KW', 'Bleicker, Tobias', 'Brünink, Sebastian', 'Schneider, Julia', 'Schmidt, Marie Luisa', 'Mulders, Daphne GJC', 'Haagmans, Bart L', 'van der Veer, Bas', 'van den Brink, Sharon', 'Wijsman, Lisa', 'Goderski, Gabriel', 'Romette, Jean-Louis', 'Ellis, Joanna', 'Zambon, Maria', 'Peiris, Malik', 'Goossens, Herman', 'Reusken, Chantal', 'Koopmans, Marion PG', 'Drosten, Christian']",Euro Surveill,,,True
d958168df85240e544a918d843a14e887dc41d2b,PMC,Note from the editors: novel coronavirus (2019-nCoV),http://dx.doi.org/10.2807/1560-7917.ES.2020.25.3.2001231,PMC6988271,31992390,CC BY,,2020 Jan 23,,Euro Surveill,,,True
28223ad437aa22ac2285bd9dd775e1415a69411a,PMC,"Real-time tentative assessment of the epidemiological characteristics of novel coronavirus infections in Wuhan, China, as at 22 January 2020",http://dx.doi.org/10.2807/1560-7917.ES.2020.25.3.2000044,PMC6988272,31992388,CC BY,"A novel coronavirus (2019-nCoV) causing severe acute respiratory disease emerged recently in Wuhan, China. Information on reported cases strongly indicates human-to-human spread, and the most recent information is increasingly indicative of sustained human-to-human transmission. While the overall severity profile among cases may change as more mild cases are identified, we estimate a risk of fatality among hospitalised cases at 14% (95% confidence interval: 3.9–32%).",2020 Jan 23,"['Wu, Peng', 'Hao, Xinxin', 'Lau, Eric H Y', 'Wong, Jessica Y', 'Leung, Kathy S M', 'Wu, Joseph T', 'Cowling, Benjamin J', 'Leung, Gabriel M']",Euro Surveill,,,True
731a1455688921b0d728c1ca833b7fa918c1e435,PMC,"Geospatial Science and Point-of-Care Testing: Creating Solutions for Population Access, Emergencies, Outbreaks, and Disasters",http://dx.doi.org/10.3389/fpubh.2019.00329,PMC6988819,32039125,CC BY,"Objectives: (a) To understand how to integrate geospatial concepts when implementing point-of-care testing (POCT); (b) to facilitate emergency, outbreak, and disaster preparedness and emergency management in healthcare small-world networks; (c) to enhance community resilience by using POCT in tandem with geographic information systems (GISs) and other geospatial tools; and (d) to advance crisis standards of care at points of need, adaptable and scalable for public health practice in limited-resource countries and other global settings. Content: Visual logistics help integrate and synthesize POCT and geospatial concepts. The resulting geospatial solutions presented here comprise: (1) small-world networks and regional topography; (2) space-time transformation, hubs, and asset mapping; (3) spatial and geospatial care paths™; (4) GIS-POCT; (5) isolation laboratories, diagnostics isolators, and mobile laboratories for highly infectious diseases; (6) alternate care facilities; (7) roaming POCT—airborne, ambulances, space, and wearables; (8) connected and wireless POCT outside hospitals; (9) unmanned aerial vehicles; (10) geospatial practice—demographic care unit resource scoring, geographic risk assessment, and national POCT policy and guidelines; (11) the hybrid laboratory; and (12) point-of-careology. Value: Small-world networks and their connectivity facilitate efficient and effective placement of POCT for optimal response, rescue, diagnosis, and treatment. Spatial care paths™ speed transport from primary encounters to referral centers bypassing topographic bottlenecks, process gaps, and time-consuming interruptions. Regional GISs position POCT close to where patients live to facilitate rapid triage, decrease therapeutic turnaround time, and conserve economic resources. Geospatial care paths™ encompass demographic and population access features. Timeliness creates value during acute illness, complex crises, and unexpected disasters. Isolation laboratories equipped with POCT help stop outbreaks and safely support critically ill patients with highly infectious diseases. POCT-enabled spatial grids can map sentinel cases and establish geographic limits of epidemics for ring vaccination. Impact: Geospatial solutions generate inherently optimal and logical placement of POCT conceptually, physically, and temporally as a means to improve crisis response and spatial resilience. If public health professionals, geospatial scientists, and POCT specialists join forces, new collaborative teamwork can create faster response and higher impact during disasters, complex crises, outbreaks, and epidemics, as well as more efficient primary, urgent, and emergency community care.",2019 Nov 26,"Kost, Gerald J.",Front Public Health,,,True
570259cab68c41a50bbfd4c998042c397bc8af33,PMC,Molecular survey and interaction of common respiratory pathogens in chicken flocks (field perspective),http://dx.doi.org/10.14202/vetworld.2019.1975-1986,PMC6989313,32095050,CC BY,"AIM: The present study was designed for the detection of the most prevalent respiratory infections in chicken flocks and clarifying their interaction and impact on flock health. MATERIALS AND METHODS: A total of 359 serum samples were collected from 55 backyard chickens and tested using commercial enzyme-linked immunosorbent assay kits to determine the seroprevalence of Newcastle disease virus (NDV), infectious bronchitis virus (IBV), influenza type A, Mycoplasma gallisepticum (MG), and Mycoplasma synoviae (MS). Molecular prevalence of NDV, IBV, low pathogenic avian influenza virus (LPAIV) H9N2, MG, and MS was carried out on swab, and tissue samples collected from 55 backyard flocks and 11 commercial broiler flocks suffered from respiratory infections using polymerase chain reaction (PCR) and reverse transcription-PCR. RESULTS: Seroprevalence of NDV, IBV, Influenza type A virus, MG, and MS in chicken backyard flocks was 56.4%, 50.9%, 12.7%, 14.5%, and 3.6%, respectively. Specific antibodies against one or more respiratory viruses and mycoplasma were detected in 36.4% of backyard flocks, indicating concurrent viral infections. The molecular survey showed that 90.9% of chicken backyard flocks were infected with common respiratory viruses (NDV, IBV, and LPAIV H9N2) while 81.8% of commercial broiler flocks were infected. The molecular prevalence rate of NDV, IBV, and LPAIV H9N2 was 46.97%, 56.1%, and 19.7% in backyard flocks, respectively. Combined viral and bacterial infection represented 40% and 63.6% of the respiratory infections, resulting in enhanced pathogenicity and increased mortalities of up to 87.5% and 27.8% in backyard and commercial flocks, respectively. Mixed infection of IBV, LPAIV H9N2, and/or Escherichia coli is the most prevalent mixed infection in broiler flocks, inducing severe clinical outcomes. Avian pathogenic E. coli was, respectively, isolated from 40% of backyard flocks and 81.82% of broiler flocks. Staphylococcus aureus was isolated from three backyard chicken flocks mixed with other respiratory pathogens with elevated mortality. Mixed infection of E. coli and MG reported in 9.1% of broiler flock. MG was detected in 14.5% of backyard flocks and 9.1% of broiler flocks while MS was detected only in 3.6% of backyard chickens mixed with E. coli, and other viruses. CONCLUSION: Our results confirm that mixed infections are more commonly prevalent and associated with dramatic exacerbation in clinical outcomes than a single infection. Bidirectional synergistic interaction between these concurrently interacted respiratory pathogens explains the severe clinical impact and high mortality rate. The high prevalence of IBV (either as a single or combined infection) with LPAIV H9N2 and/or E. coli, in spite of intensive use of commercial vaccines, increases the need for revising vaccination programs and the application of standard biosecurity measures. Backyard chickens impose a great risk and threaten commercial flocks due to the high prevalence of viral respiratory pathogens.",2019 Dec 16,"['Abdelaziz, Adel M.', 'Mohamed, Mahmoud H. A.', 'Fayez, Mahmoud M.', 'Al-Marri, Theeb', 'Qasim, Ibrahim', 'Al-Amer, Abdul Aziz']",Vet World,,,True
47ebee5001b67e76858ed1b783712a6095d00ea6,PMC,Hepatitis E Virus Cysteine Protease Has Papain Like Properties Validated by in silico Modeling and Cell-Free Inhibition Assays,http://dx.doi.org/10.3389/fcimb.2019.00478,PMC6989534,32039053,CC BY,"Hepatitis E virus (HEV) has emerged as a global health concern during the last decade. In spite of a high mortality rate in pregnant women with fulminant hepatitis, no antiviral drugs or licensed vaccine is available in India. HEV-protease is a pivotal enzyme responsible for ORF1 polyprotein processing leading to cleavage of the non-structural enzymes involved in virus replication. HEV-protease region encoding 432–592 amino acids of Genotype-1 was amplified, expressed in Sf21 cells and purified in its native form. The recombinant enzyme was biochemically characterized using SDS-PAGE, Western blotting and Immunofluorescence. The enzyme activity and the inhibition studies were conducted using Zymography, FTC-casein based protease assay and ORF1 polyprotein digestion. To conduct ORF1 digestion assay, the polyprotein, natural substrate of HEV-protease, was expressed in E. coli and purified. Cleavage of 186 kDa ORF1 polyprotein by the recombinant HEV-protease lead to appearance of non-structural proteins viz. Methyltransferase, Protease, Helicase and RNA dependent RNA polymerase which were confirmed through immunoblotting using antibodies generated against specific epitopes of the enzymes. FTC-casein substrate was used for kinetic studies to determine Km and Vmax of the enzyme and also the effect of different metal ions and other protease inhibitors. A 95% inhibition was observed with E-64 which was validated through in silico analysis. The correlation coefficient between inhibition and docking score of Inhibitors was found to have a significant value of r(2) = 0.75. The predicted 3D model showed two domain architecture structures similar to Papain like cysteine protease though they differed in arrangements of alpha helices and beta sheets. Hence, we propose that HEV-protease has characteristics of “Papain-like cysteine protease,” as determined through structural homology, active site residues and class-specific inhibition. However, conclusive nature of the enzyme remains to be established.",2020 Jan 23,"['Saraswat, Shweta', 'Chaudhary, Meenakshi', 'Sehgal, Deepak']",Front Cell Infect Microbiol,,,False
ac5854f7ef4751d0a621fafd02e4cd05b08321cb,PMC,Hepatitis E Virus Cysteine Protease Has Papain Like Properties Validated by in silico Modeling and Cell-Free Inhibition Assays,http://dx.doi.org/10.3389/fcimb.2019.00478,PMC6989534,32039053,CC BY,"Hepatitis E virus (HEV) has emerged as a global health concern during the last decade. In spite of a high mortality rate in pregnant women with fulminant hepatitis, no antiviral drugs or licensed vaccine is available in India. HEV-protease is a pivotal enzyme responsible for ORF1 polyprotein processing leading to cleavage of the non-structural enzymes involved in virus replication. HEV-protease region encoding 432–592 amino acids of Genotype-1 was amplified, expressed in Sf21 cells and purified in its native form. The recombinant enzyme was biochemically characterized using SDS-PAGE, Western blotting and Immunofluorescence. The enzyme activity and the inhibition studies were conducted using Zymography, FTC-casein based protease assay and ORF1 polyprotein digestion. To conduct ORF1 digestion assay, the polyprotein, natural substrate of HEV-protease, was expressed in E. coli and purified. Cleavage of 186 kDa ORF1 polyprotein by the recombinant HEV-protease lead to appearance of non-structural proteins viz. Methyltransferase, Protease, Helicase and RNA dependent RNA polymerase which were confirmed through immunoblotting using antibodies generated against specific epitopes of the enzymes. FTC-casein substrate was used for kinetic studies to determine Km and Vmax of the enzyme and also the effect of different metal ions and other protease inhibitors. A 95% inhibition was observed with E-64 which was validated through in silico analysis. The correlation coefficient between inhibition and docking score of Inhibitors was found to have a significant value of r(2) = 0.75. The predicted 3D model showed two domain architecture structures similar to Papain like cysteine protease though they differed in arrangements of alpha helices and beta sheets. Hence, we propose that HEV-protease has characteristics of “Papain-like cysteine protease,” as determined through structural homology, active site residues and class-specific inhibition. However, conclusive nature of the enzyme remains to be established.",2020 Jan 23,"['Saraswat, Shweta', 'Chaudhary, Meenakshi', 'Sehgal, Deepak']",Front Cell Infect Microbiol,,,True
be5a6b0a0bff9b130578c5ad71a6be32d16525d6,PMC,Transmissible Gastroenteritis Virus Infection Up-Regulates FcRn Expression via Nucleocapsid Protein and Secretion of TGF-β in Porcine Intestinal Epithelial Cells,http://dx.doi.org/10.3389/fmicb.2019.03085,PMC6990134,32038538,CC BY,"Transmissible gastroenteritis virus (TGEV) is a porcine intestinal coronavirus that causes fatal severe watery diarrhea in piglets. The neonatal Fc receptor (FcRn) is the only IgG transport receptor, its expression on mucosal surfaces is triggered upon viral stimulation, which significantly enhances mucosal immunity. We utilized TGEV as a model pathogen to explore the role of FcRn in resisting viral invasion in overall intestinal mucosal immunity. TGEV induced FcRn expression by activating NF-κB signaling in porcine small intestinal epithelial (IPEC-J2) cells, however, the underlying mechanisms are unclear. First, using small interfering RNAs, we found that TGEV up-regulated FcRn expression via TLR3, TLR9 and RIG-I. Moreover, TGEV induced IL-1β, IL-6, IL-8, TGF-β, and TNF-α production. TGF-β-stimulated IPEC-J2 cells highly up-regulated FcRn expression, while treatment with a JNK-specific inhibitor down-regulated the expression. TGEV nucleocapsid (N) protein also enhanced FcRn promoter activity via the NF-κB signaling pathway and its central region (aa 128–252) was essential for FcRn activation. Additionally, N protein-mediated FcRn up-regulation promotes IgG transcytosis. Thus, TGEV N protein and TGF-β up-regulated FcRn expression, further clarifying the molecular mechanism of up-regulation of FcRn expression by TGEV.",2020 Jan 21,"['Qian, Shaoju', 'Gao, Zitong', 'Cao, Rui', 'Yang, Kang', 'Cui, Yijie', 'Li, Shaowen', 'Meng, Xianrong', 'He, Qigai', 'Li, Zili']",Front Microbiol,,,True
7bd92243bc19bc49fe89f6dc278614adf8cbdf4b,PMC,"The year 2020, a milestone in breaking the vicious cycle of poverty and illness in China",http://dx.doi.org/10.1186/s40249-020-0626-5,PMC6990531,31996258,CC BY,"Marking the end of the five-year programme initiated by the Chinese Government to lift more than 70 million people out of poverty, the year 2020 is a milestone. Poverty alleviation has moved strongly forward in China and the major health indicators are now better than the average of all middle- and high-income countries. However, the dual burden of infectious and chronic diseases remains a challenge with respect to achieving the health target in the United Nations 2030 Agenda for sustainable development goals (SDGs). In 2015, about 44% of the poor population in China were impoverished by illness but already in 2018, multi-sectoral actions delivered by the Health-related Poverty Alleviation programme had reduced the number almost by half. In the past three years 15 million poor people (98% of the poor population) with infectious and chronic diseases had been treated and taken care of thanks to financial support through multiple health insurance schemes and other governmental subsidies. This article discusses the lessons learnt with regard to health-related poverty alleviation in China with special reference to those still remaining impoverished by illness. Consolidation of the achievements reached and provision of basic needs to those still disadvantaged and in poor health will require a major improvement of accessibility to, and affordability of, health services. The next step towards enhanced productivity and better living conditions will involve upgrading of the capacity of health professionals in the poor regions, promotion of coherent efforts in health-related poverty alleviation and rural revitalization measures. As an additional measure, data monitoring and research on health poverty alleviation should be strengthened as they are essential to generate the evidence and knowledge needed to support the move in the direction envisioned by the SDGs, and the new Healthy China 2030 programme.",2020 Jan 30,"['Wang, Yun-Ping', 'Zhou, Xiao-Nong']",Infect Dis Poverty,,,True
38c9ad4d6eb48945732f8519c795b39b4bdb0c93,PMC,Reassessing therapeutic antibodies for neglected and tropical diseases,http://dx.doi.org/10.1371/journal.pntd.0007860,PMC6991954,31999695,CC BY,"In the past two decades there has been a significant expansion in the number of new therapeutic monoclonal antibodies (mAbs) that are approved by regulators. The discovery of these new medicines has been driven primarily by new approaches in inflammatory diseases and oncology, especially in immuno-oncology. Other recent successes have included new antibodies for use in viral diseases, including HIV. The perception of very high costs associated with mAbs has led to the assumption that they play no role in prophylaxis for diseases of poverty. However, improvements in antibody-expression yields and manufacturing processes indicate this is a cost-effective option for providing protection from many types of infection that should be revisited. Recent technology developments also indicate that several months of protection could be achieved with a single dose. Moreover, new methods in B cell sorting now enable the systematic identification of high-quality antibodies from humanized mice, or patients. This Review discusses the potential for passive immunization against schistosomiasis, fungal infections, dengue, and other neglected diseases.",2020 Jan 30,"['Hooft van Huijsduijnen, Rob', 'Kojima, Somei', 'Carter, Dee', 'Okabe, Hisafumi', 'Sato, Akihide', 'Akahata, Wataru', 'Wells, Timothy N. C.', 'Katsuno, Kei']",PLoS Negl Trop Dis,,,True
c2952e4d56bd9bf5c6eee0aaa733557471e60a92,PMC,Discovery of Bat Coronaviruses through Surveillance and Probe Capture-Based Next-Generation Sequencing,http://dx.doi.org/10.1128/mSphere.00807-19,PMC6992374,31996413,CC BY,"Coronaviruses (CoVs) of bat origin have caused two pandemics in this century. Severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV both originated from bats, and it is highly likely that bat coronaviruses will cause future outbreaks. Active surveillance is both urgent and essential to predict and mitigate the emergence of these viruses in humans. Next-generation sequencing (NGS) is currently the preferred methodology for virus discovery to ensure unbiased sequencing of bat CoVs, considering their high genetic diversity. However, unbiased NGS is an expensive methodology and is prone to missing low-abundance CoV sequences due to the high background level of nonviral sequences present in surveillance field samples. Here, we employ a capture-based NGS approach using baits targeting most of the CoV species. Using this technology, we effectively reduced sequencing costs by increasing the sensitivity of detection. We discovered nine full genomes of bat CoVs in this study and revealed great genetic diversity for eight of them. IMPORTANCE Active surveillance is both urgent and essential to predict and mitigate the emergence of bat-origin CoV in humans and livestock. However, great genetic diversity increases the chance of homologous recombination among CoVs. Performing targeted PCR, a common practice for many surveillance studies, would not reflect this diversity. NGS, on the other hand, is an expensive methodology and is prone to missing low-abundance CoV sequences. Here, we employ a capture-based NGS approach using baits targeting all CoVs. Our work demonstrates that targeted, cost-effective, large-scale, genome-level surveillance of bat CoVs is now highly feasible.",2020 Jan 29,"['Li, Bei', 'Si, Hao-Rui', 'Zhu, Yan', 'Yang, Xing-Lou', 'Anderson, Danielle E.', 'Shi, Zheng-Li', 'Wang, Lin-Fa', 'Zhou, Peng']",mSphere,,,True
b7b122d6d4cc409f7a22bec63936640b4cd0f334,PMC,"Regulation of the ER Stress Response by the Ion Channel Activity of the Infectious Bronchitis Coronavirus Envelope Protein Modulates Virion Release, Apoptosis, Viral Fitness, and Pathogenesis",http://dx.doi.org/10.3389/fmicb.2019.03022,PMC6992538,32038520,CC BY,"Coronavirus (CoV) envelope (E) protein is a small structural protein critical for virion morphogenesis and release. The recently characterized E protein ion channel activity (EIC) has also been implicated in modulating viral pathogenesis. In this study, we used infectious bronchitis coronavirus (IBV) as a model to study EIC. Two recombinant IBVs (rIBVs) harboring EIC-inactivating mutations – rT16A and rA26F – were serially passaged, and several compensatory mutations were identified in the transmembrane domain (TMD). Two rIBVs harboring these putative EIC-reverting mutations – rT16A/A26V and rA26F/F14N – were recovered. Compared with the parental rIBV-p65 control, all four EIC mutants exhibited comparable levels of intracellular RNA synthesis, structural protein production, and virion assembly. Our results showed that the IBV EIC contributed to the induction of ER stress response, as up-regulation of ER stress-related genes was markedly reduced in cells infected with the EIC-defective mutants. EIC-defective mutants also formed smaller plaques, released significantly less infectious virions into the culture supernatant, and had lower levels of viral fitness in cell culture. Significantly, all these defective phenotypes were restored in cells infected with the putative EIC revertants. EIC mutations were also implicated in regulating IBV-induced apoptosis, induction of pro-inflammatory cytokines, and viral pathogenicity in vivo. Taken together, this study highlights the importance of CoV EIC in modulating virion release and various aspects of CoV – host interaction.",2020 Jan 24,"['Li, Shumin', 'Yuan, Lixia', 'Dai, Guo', 'Chen, Rui Ai', 'Liu, Ding Xiang', 'Fung, To Sing']",Front Microbiol,,,True
6d756b7df1778be58daa0e30caefc968807d6a80,PMC,"A chromosome-scale genome assembly of Isatis indigotica, an important medicinal plant used in traditional Chinese medicine: An Isatis genome",http://dx.doi.org/10.1038/s41438-020-0240-5,PMC6994597,32025321,CC BY,"Isatis indigotica (2n = 14) is an important medicinal plant in China. Its dried leaves and roots (called Isatidis Folium and Isatidis Radix, respectively) are broadly used in traditional Chinese medicine for curing diseases caused by bacteria and viruses such as influenza and viral pneumonia. Various classes of compounds isolated from this species have been identified as effective ingredients. Previous studies based on transcriptomes revealed only a few candidate genes for the biosynthesis of these active compounds in this medicinal plant. Here, we report a high-quality chromosome-scale genome assembly of I. indigotica with a total size of 293.88 Mb and scaffold N50 = 36.16 Mb using single-molecule real-time long reads and high-throughput chromosome conformation capture techniques. We annotated 30,323 high-confidence protein-coding genes. Based on homolog searching and functional annotations, we identified many candidate genes involved in the biosynthesis of main active components such as indoles, terpenoids, and phenylpropanoids. In addition, we found that some key enzyme-coding gene families related to the biosynthesis of these components were expanded due to tandem duplications, which likely drove the production of these major active compounds and explained why I. indigotica has excellent antibacterial and antiviral activities. Our results highlighted the importance of genome sequencing in identifying candidate genes for metabolite synthesis in medicinal plants.",2020 Feb 1,"['Kang, Minghui', 'Wu, Haolin', 'Yang, Qiao', 'Huang, Li', 'Hu, Quanjun', 'Ma, Tao', 'Li, Zaiyun', 'Liu, Jianquan']",Hortic Res,,,True
26300f1df41b1308ba14cd9d83f7729a52283e7f,PMC,Cyclodextrins: Emerging Medicines of the New Millennium,http://dx.doi.org/10.3390/biom9120801,PMC6995511,31795222,CC BY,"Cyclodextrins, since their discovery in the late 19th century, were mainly regarded as excipients. Nevertheless, developments in cyclodextrin research have shown that some of these hosts can capture and include biomolecules, highlighting fatty acids and cholesterol, which implies that they are not inert and that their action may be used in specific medicinal purposes. The present review, centered on literature reports from the year 2000 until the present day, presents a comprehensive description of the known biological activities of cyclodextrins and their implications for medicinal applications. The paper is divided into two main sections, one devoted to the properties and applications of cyclodextrins as active pharmaceutical ingredients in a variety of pathologies, from infectious ailments to cardiovascular dysfunctions and metabolic diseases. The second section is dedicated to the use of cyclodextrins in a range of biomedical technologies.",2019 Nov 28,"Braga, Susana Santos",Biomolecules,,,True
c56e3599cec6dd5161af736e9d9cbd0e58c86315,PMC,Novel Variants of Angiotensin Converting Enzyme-2 of Shorter Molecular Size to Target the Kidney Renin Angiotensin System,http://dx.doi.org/10.3390/biom9120886,PMC6995632,31861139,CC BY,"ACE2 is a monocarboxypeptidase which generates Angiotensin (1–7) from Angiotensin II (1–8). Attempts to target the kidney Renin Angiotensin System using native ACE2 to treat kidney disease are hampered by its large molecular size, 100 kDa, which precludes its glomerular filtration and subsequent tubular uptake. Here, we show that both urine and kidney lysates are capable of digesting native ACE2 into shorter proteins of ~60–75 kDa and then demonstrate that they are enzymatically very active. We then truncated the native ACE2 by design from the C-terminus to generate two short recombinant (r)ACE2 variants (1-605 and 1-619AA). These two truncates have a molecular size of ~70 kDa, as expected from the amino acid sequence and as shown by Western blot. ACE2 enzyme activity, measured using a specific substrate, was higher than that of the native rACE2 (1-740 AA). When infused to mice with genetic ACE2 deficiency, a single i.v. injection of 1-619 resulted in detectable ACE2 activity in urine, whereas infusion of the native ACE2 did not. Moreover, ACE2 activity was recovered in harvested kidneys from ACE2-deficient mice infused with 1-619, but not in controls (23.1 ± 4.3 RFU/µg creatinine/h and 1.96 ± 0.73 RFU/µg protein/hr, respectively). In addition, the kidneys of ACE2-null mice infused with 1-619 studied ex vivo formed more Ang (1–7) from exogenous Ang II than those infused with vehicle (AUC 8555 ± 1933 vs. 3439 ± 753 ng/mL, respectively, p < 0.05) further demonstrating the functional effect of increasing kidney ACE2 activity after the infusion of our short ACE2 1-619 variant. We conclude that our novel short recombinant ACE2 variants undergo glomerular filtration, which is associated with kidney uptake of enzymatically active proteins that can enhance the formation of Ang (1–7) from Ang II. These small ACE2 variants may offer a potentially useful approach to target kidney RAS overactivity to combat kidney injury.",2019 Dec 17,"['Wysocki, Jan', 'Schulze, Arndt', 'Batlle, Daniel']",Biomolecules,,,True
b0ac4fa0057eccfcc5b495fb2172045d301876be,PMC,Novel Variants of Angiotensin Converting Enzyme-2 of Shorter Molecular Size to Target the Kidney Renin Angiotensin System,http://dx.doi.org/10.3390/biom9120886,PMC6995632,31861139,CC BY,"ACE2 is a monocarboxypeptidase which generates Angiotensin (1–7) from Angiotensin II (1–8). Attempts to target the kidney Renin Angiotensin System using native ACE2 to treat kidney disease are hampered by its large molecular size, 100 kDa, which precludes its glomerular filtration and subsequent tubular uptake. Here, we show that both urine and kidney lysates are capable of digesting native ACE2 into shorter proteins of ~60–75 kDa and then demonstrate that they are enzymatically very active. We then truncated the native ACE2 by design from the C-terminus to generate two short recombinant (r)ACE2 variants (1-605 and 1-619AA). These two truncates have a molecular size of ~70 kDa, as expected from the amino acid sequence and as shown by Western blot. ACE2 enzyme activity, measured using a specific substrate, was higher than that of the native rACE2 (1-740 AA). When infused to mice with genetic ACE2 deficiency, a single i.v. injection of 1-619 resulted in detectable ACE2 activity in urine, whereas infusion of the native ACE2 did not. Moreover, ACE2 activity was recovered in harvested kidneys from ACE2-deficient mice infused with 1-619, but not in controls (23.1 ± 4.3 RFU/µg creatinine/h and 1.96 ± 0.73 RFU/µg protein/hr, respectively). In addition, the kidneys of ACE2-null mice infused with 1-619 studied ex vivo formed more Ang (1–7) from exogenous Ang II than those infused with vehicle (AUC 8555 ± 1933 vs. 3439 ± 753 ng/mL, respectively, p < 0.05) further demonstrating the functional effect of increasing kidney ACE2 activity after the infusion of our short ACE2 1-619 variant. We conclude that our novel short recombinant ACE2 variants undergo glomerular filtration, which is associated with kidney uptake of enzymatically active proteins that can enhance the formation of Ang (1–7) from Ang II. These small ACE2 variants may offer a potentially useful approach to target kidney RAS overactivity to combat kidney injury.",2019 Dec 17,"['Wysocki, Jan', 'Schulze, Arndt', 'Batlle, Daniel']",Biomolecules,,,False
0fdba4c24e81ec738a498e2ffa501d46c22745a6,PMC,The expression patterns of immune response genes in the Peripheral Blood Mononuclear cells of pregnant women presenting with subclinical or clinical HEV infection are different and trimester-dependent: A whole transcriptome analysis,http://dx.doi.org/10.1371/journal.pone.0228068,PMC6996850,32012176,CC BY,"Hepatitis E is an enteric disease highly prevalent in the developing countries. The basis for high mortality among pregnant hepatitis E patients remains unclear. Importantly, a large proportion of infected pregnant women present with subclinical infection as well. In order to understand the possible mechanisms influencing clinical presentation of hepatitis E in pregnant women, we explored a system biology approach. For this, PBMCs from various categories were subjected to RNAseq analysis. These included non-pregnant (NPR, acute and convalescent phases) and pregnant (PR, 2(nd) and 3(rd) trimesters, acute phase and subclinical HEV infections) patients and corresponding healthy controls. The current study deals with immune response genes. In contrast to exclusive up-regulation of nonspecific, early immune response transcripts in the NPR patients, the PR patients exhibited broader and heightened expression of genes associated with innate as well as adaptive T and B cell responses. The study identified for the first time (1) inverse relationship of immunoglobulin (Ig) genes overexpression and (2) association of differential expression of S100 series genes with disease presentation. The data suggests possible involvement of TLR4 and NOD1 in pregnant patients and alpha defensins in all patient categories suggesting a role in protection. Induction of IFNγ gene was not detected during the acute phase irrespective of pregnancy. Association of response to vitamin D, transcripts related to NK/NKT and regulatory T cells during subclinical infection are noteworthy. The data obtained here could be correlated with several studies reported earlier in hepatitis E patients suggesting utility of PBMCs as an alternate specimen. The extensive, informative data provided here for the first time should form basis for future studies that will help in understanding pathogenesis of fulminant hepatitis E.",2020 Feb 3,"['Ramdasi, Ashwini Y.', 'Arankalle, Vidya A.']",PLoS One,,,True
98f3c099dcd497b42efa3082b1e631d07378a5e5,PMC,Qualitative Research: Institutional Preparedness During Threats of Infectious Disease Outbreaks,http://dx.doi.org/10.1155/2020/5861894,PMC6998699,32090099,CC BY,"BACKGROUND: As demonstrated during the global Ebola crisis of 2014–2016, healthcare institutions in high resource settings need support concerning preparedness during threats of infectious disease outbreaks. This study aimed to exploratively develop a standardized preparedness system to use during unfolding threats of severe infectious diseases. METHODS: A qualitative three-step study among infectious disease prevention and control experts was performed. First, interviews (n = 5) were conducted to identify which factors trigger preparedness activities during an unfolding threat. Second, these triggers informed the design of a phased preparedness system which was tested in a focus group discussion (n = 5) were conducted to identify which factors trigger preparedness activities during an unfolding threat. Second, these triggers informed the design of a phased preparedness system which was tested in a focus group discussion (n = 5) were conducted to identify which factors trigger preparedness activities during an unfolding threat. Second, these triggers informed the design of a phased preparedness system which was tested in a focus group discussion ( RESULTS: Four preparedness phases were identified: preparedness phase green is a situation without the presence of the infectious disease threat that requires centralized care, anywhere in the world. Phase yellow is an outbreak in the world with some likelihood of imported cases. Phase orange is a realistic chance of an unexpected case within the country, or unrest developing among population or staff; phase red is cases admitted to hospitals in the country, potentially causing a shortage of resources. Specific preparedness activities included infection prevention, diagnostics, patient care, staff, and communication. Consensus was reached on the need for the development of a preparedness system and national coordination during threats. CONCLUSIONS: In this study, we developed a standardized system to support institutional preparedness during an increasing threat. Use of this system by both curative healthcare institutions and the (municipal) public health service, could help to effectively communicate and align preparedness activities during future threats of severe infectious diseases.",2020 Jan 23,"['de Rooij, Doret', 'Belfroid, Evelien', 'Eilers, Renske', 'Roßkamp, Dorothee', 'Swaan, Corien', 'Timen, Aura']",Biomed Res Int,,,True
acae9ff2aa45fe67cf994e18c4e7e8d95353b0c2,PMC,Plasmodium falciparum pre-erythrocytic stage vaccine development,http://dx.doi.org/10.1186/s12936-020-3141-z,PMC6998842,32013956,CC BY,"Worldwide strategies between 2010 and 2017 aimed at controlling malarial parasites (mainly Plasmodium falciparum) led to a reduction of just 18% regarding disease incidence rates. Many biologically-derived anti-malarial vaccine candidates have been developed to date; this has involved using many experimental animals, an immense amount of work and the investment of millions of dollars. This review provides an overview of the current state and the main results of clinical trials for sporozoite-targeting vaccines (i.e. the parasite stage infecting the liver) carried out by research groups in areas having variable malaria transmission rates. However, none has led to promising results regarding the effective control of the disease, thereby making it necessary to complement such efforts at finding/introducing new vaccine candidates by adopting a multi-epitope, multi-stage approach, based on minimal subunits of the main sporozoite proteins involved in the invasion of the liver.",2020 Feb 3,"['Molina-Franky, Jessica', 'Cuy-Chaparro, Laura', 'Camargo, Anny', 'Reyes, César', 'Gómez, Marcela', 'Salamanca, David Ricardo', 'Patarroyo, Manuel Alfonso', 'Patarroyo, Manuel Elkin']",Malar J,,,True
6f67e5b5e61f9ce94ddc8aaae34799a81c4c213d,PMC,Porcine β-defensin 2 inhibits proliferation of pseudorabies virus in vitro and in transgenic mice,http://dx.doi.org/10.1186/s12985-020-1288-4,PMC6998849,32014007,CC BY,"BACKGROUND: Porcine β-defensin 2 (PBD-2), produced by host cells, is an antimicrobial cysteine-rich cationic peptide with multi-functions. Previous studies have demonstrated that PBD-2 can kill various bacteria, regulate host immune responses and promote growth of piglets. However, the antiviral role of PBD-2 is rarely investigated. This study aimed to reveal the antiviral ability of PBD-2 against pseudorabies virus (PRV), the causative pathogen of Aujeszky’s disease, in PK-15 cells and in a PBD-2 expressing transgenic (TG) mouse model. METHODS: In this study, the cytotoxicity of PBD-2 on PK-15 cells was measured by CCK-8 assay. PK-15 cells were incubated with PRV pre-treated with different concentrations of PBD-2 and PRV titers in cell culture supernatants were determined by real-time quantitative PCR (RT-qPCR). TG mice and wild-type (WT) mice were intraperitoneally injected with PRV and the survival rate was recorded for 10 days. Meanwhile, tissue lesions in brain, spleen and liver of infected mice were observed and the viral loads of PRV in brain, liver and lung were analyzed by RT-qPCR. RESULTS: PBD-2 at a maximum concentration of 80 μg/mL displayed no significant cytotoxicity on PK-15 cells. A threshold concentration of PBD-2 at 40 μg/mL was required to inhibit PRV proliferation in PK-15 cells. The survival rate in PBD-2 TG mice was 50% higher than that of WT mice. In addition, TG mice showed alleviated tissue lesions in brain, spleen and liver compared with their WT littermates after PRV challenge, while viral loads of PRV in brain, liver and lung of TG mice were significantly lower than that of WT mice. CONCLUSIONS: PBD-2 could inhibit PRV proliferation in PK-15 cells and protect mice from PRV infection, which confirmed the antiviral ability of PBD-2 both in vitro and in vivo. The application of PBD-2 in developing anti-viral drugs or disease-resistant animals can be further investigated.",2020 Feb 3,"['Huang, Jing', 'Qi, Yanhua', 'Wang, Antian', 'Huang, Chao', 'Liu, Xiao', 'Yang, Xi', 'Li, Lu', 'Zhou, Rui']",Virol J,,,True
c9fee561c2a3834645dbb61dc4ae6448051da492,PMC,Comprehensive Genomic Characterization Analysis of lncRNAs in Cells With Porcine Delta Coronavirus Infection,http://dx.doi.org/10.3389/fmicb.2019.03036,PMC6999024,32063887,CC BY,"Porcine delta coronavirus (PDCoV) is a novel emerging enterocytetropic virus causing diarrhea, vomiting, dehydration, and mortality in suckling piglets. Long non-coding RNAs (lncRNAs) are known to be important regulators during virus infection. Here, we describe a comprehensive transcriptome profile of lncRNA in PDCoV-infected swine testicular (ST) cells. In total, 1,308 annotated and 1,190 novel lncRNA candidate sequences were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these lncRNAs might be involved in numerous biological processes. Clustering analysis of differentially expressed lncRNAs showed that 454 annotated and 376 novel lncRNAs were regulated after PDCoV infection. Furthermore, we constructed a lncRNA-protein-coding gene co-expression interaction network. The KEGG analysis of the co-expressed genes showed that these differentially expressed lncRNAs were enriched in pathways related to metabolism and TNF signaling. Our study provided comprehensive information about lncRNAs that would be a useful resource for studying the pathogenesis of and designing antiviral therapy for PDCoV infection.",2020 Jan 28,"['Liu, Junli', 'Wang, Fangfang', 'Du, Liuyang', 'Li, Juan', 'Yu, Tianqi', 'Jin, Yulan', 'Yan, Yan', 'Zhou, Jiyong', 'Gu, Jinyan']",Front Microbiol,,,True
eddf68bf069ab23f6fbe7c7ab16c1c49335f4de9,PMC,Magnetic Nanotrap Particles Preserve the Stability of Venezuelan Equine Encephalitis Virus in Blood for Laboratory Detection,http://dx.doi.org/10.3389/fvets.2019.00509,PMC6999085,32064269,CC BY,"Most of the modern techniques used for identification of viral-induced disease are based on identification of viral antigens and/or nucleic acids in patient's blood. Diagnosis in the field or in remote locations can be challenging and alternatively samples are shipped to diagnostic labs for testing. Shipments must occur under controlled temperature conditions to prevent loss of sample integrity. We have tested the ability of magnetic Nanotrap® (NT) particles to improve stability and detection of Venezuelan equine encephalitis virus (VEEV), viral capsid protein, and viral genomic RNA in whole human blood at elevated temperature and prolonged storage conditions. NT particles have previously been shown to capture and enrich multiple pathogens including respiratory syncytial virus, influenza virus, coronavirus, and Rift Valley fever virus. Our study indicates that samples incubated with NT particles had detectable levels of infectious VEEV in blood equal to or greater than samples without NT treatment across all temperatures. Viral RNA detection was increased in the presence of NT particles at later time points (72 h) and higher temperature (40°C) conditions. Likewise, detection of VEEV capsid protein was enhanced in the presence of NT particles up to 72 h at 40°C. Finally, we intranasally infected C3H mice with TC-83, the live attenuated vaccine strain of VEEV, and demonstrated that NT particles could substantially increase the detection of VEEV capsid in infected blood incubated up to 72 h at 40°C. Samples without NT particles had undetectable capsid protein levels. Taken together, our data demonstrate the ability of NT particles to preserve and enable detection of VEEV in human and mouse blood samples over time and at elevated temperatures.",2020 Jan 28,"['Akhrymuk, Ivan', 'Lin, Shih-Chao', 'Sun, Mei', 'Patnaik, Anurag', 'Lehman, Caitlin', 'Altamura, Louis', 'Minogue, Timothy', 'Lepene, Ben', 'van Hoek, Monique L.', 'Kehn-Hall, Kylene']",Front Vet Sci,,,True
5503464f5c8ac4db987ce87b05f224a7aaafc1a7,PMC,Isolation and Selection of Duck Primary Cells as Pathogenic and Innate Immunologic Cell Models for Duck Plague Virus,http://dx.doi.org/10.3389/fimmu.2019.03131,PMC6999086,32063900,CC BY,"Duck plague virus (DPV) is a representative pathogen transmitted among aquatic animals that causes gross lesions and immune inhibition in geese and ducks. The mechanism of organ tropism and innate immune evasion of DPV has not been completely deciphered due to a lack of cell models to study the innate immune manipulation and pathogenicity of aquatic viruses. In the present study, we isolated five types of duck primary cells [duck embryo fibroblasts (DEFs), neurons, astrocytes, peripheral blood mononuclear cells (PBMCs), and monocytes/macrophages] to identify appropriate cell models for DPV, using tropism infection and innate immunologic assays. Cells responded differently to stimulation with DNA viruses or RNA virus analogs. DPV infection exhibited broad tropism, as the recombinant virulent strain (CHv-GFP) infected DEFs, neurons, astrocytes, and monocytes/macrophages, but not the PBMCs, as the expression of EGFP was negligible. The basal levels of innate immunity molecules were highest in monocytes/macrophages and lower in DEFs and astrocytes. Conversely, the titer and genomic copy number of the attenuated virus strain was higher in DEFs and astrocytes than in neurons and monocytes/macrophages. The titer and genomic copy number of the attenuated virus strain were higher compared with the virulent strain in DEFs, neurons, and astrocytes. The innate immune response was not significantly induced by either DPV strain in DEFs, neurons, or astrocytes. The virulent strain persistently infected monocytes/macrophages, but the attenuated strain did so abortively, and this was accompanied by the phenomenon of innate immune inhibition and activation by the virulent and attenuated strains, respectively. Blockage of IFNAR signaling promoted replication of the attenuated strain. Pre-activation of IFNAR signaling inhibited infection by the virulent strain. The selection assay results indicated that induction of innate immunity plays an essential role in controlling DPV infection, and monocytes/macrophages are an important cell model for further investigations. Our study provided practical methods for isolating and culturing duck primary cells, and our results will facilitate further investigations of organ tropism, innate immune responses, latent infection, and the effectiveness of antiviral drugs for treating DPV and potentially other aerial bird pathogens.",2020 Jan 28,"['Tian, Bin', 'Cai, Dongjie', 'He, Tianqiong', 'Deng, Liyao', 'Wu, Liping', 'Wang, Mingshu', 'Jia, Renyong', 'Zhu, Dekang', 'Liu, Mafeng', 'Yang, Qiao', 'Wu, Ying', 'Zhao, Xinxin', 'Chen, Shun', 'Zhang, Shaqiu', 'Huang, Juan', 'Ou, Xumin', 'Mao, Sai', 'Yu, Yanling', 'Zhang, Ling', 'Liu, Yunya', 'Cheng, Anchun']",Front Immunol,,,True
d8ffe10c4c92236a38d1d27b1c0d7575b7672ed0,PMC,"Viral etiology of pneumonia among severely malnourished under-five children in an urban hospital, Bangladesh",http://dx.doi.org/10.1371/journal.pone.0228329,PMC6999894,32017782,CC BY,"BACKGROUND: In Bangladesh, pneumonia has a higher mortality among malnourished children aged <5 years. Evaluating pneumonia etiology among malnourished children may help improve empiric treatment guidelines. METHODS: During April 2015—December 2017, we conducted a case-control study among severe acute malnourished (SAM) children aged <5 years admitted to the Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). We enrolled hospital admitted SAM children with clinical or radiological pneumonia as cases (during April 2015 to March 2017) and hospital admitted SAM children without any respiratory symptom in the past 10 days before admission as controls (during February 2016 to December 2017). We tested nasopharyngeal wash from both case and control for respiratory syncytial virus (RSV), human metapneumovirus (HMPV), influenza viruses, human parainfluenza viruses (HPIV), rhinovirus and adenovirus by singleplex real-time reverse transcriptase polymerase chain reaction. To identify the independent association of pneumonia with viral pathogens during February 2016 to March 2017, we used multivariable logistic regression for calculating adjusted odds ratios. RESULTS: We enrolled 360 cases and 334 controls. For case and control the median age was 8 months (IQR: 5–13) and 11 months (IQR: 6–18) (p = 0.001) respectively. Weight/age Z-score was -4.3 (SD ±0.7) for cases and -4.1 (SD ±1.1) for controls (p = 0.01). Among cases 68% had both clinical and radiological pneumonia, 1% had clinical pneumonia and 31% had only radiological pneumonia. Respiratory virus detection was high in cases compared to controls [69.9% (251) vs. 44.8% (148), p = 0.0001]. The most frequently detected viruses among cases were rhinoviruses (79, 22.0%) followed by RSV (32, 8.9%), adenovirus (23, 6.4%), HPIV (22, 6.1%), influenza virus (16, 4.5%), and HMPV (16, 4.5%). Among the controls, rhinoviruses (82, 24.8%) were most commonly detected one followed by adenovirus (26,7.9%), HMPV (5, 1.5%), HPIV (4, 1.2%), RSV (3, 0.9%), and influenza virus (2, 0.6%). RSV (OR 13.1; 95% CI: 1.6, 106.1), influenza virus (OR 8.7; 95% CI: 1.0, 78.9), HPIV (3.8; 95% CI: 1.0, 14.8), and HMPV (2.7; 95% CI: 1.3, 5.5) were independently associated with pneumonia while compared between 178 cases and 174 controls. CONCLUSION: Viral etiology of pneumonia in SAM children were mainly attributable to RSV, influenza, HPIV and HMPV. Our study findings may help in planning further studies targeting vaccines or drugs against common respiratory viruses responsible for pneumonia among SAM children.",2020 Feb 4,"['Chowdhury, Fahmida', 'Shahid, Abu Sadat Mohammad Sayeem Bin', 'Ghosh, Probir Kumar', 'Rahman, Mustafizur', 'Hassan, Md. Zakiul', 'Akhtar, Zubair', 'Muneer, S. Mah-E-', 'Shahrin, Lubaba', 'Ahmed, Tahmeed', 'Chisti, Mohammod Jobayer']",PLoS One,,,True
cac106b063755a144ec1154f593d78d5a4f6f4c1,PMC,Porcine transmissible gastroenteritis virus nonstructural protein 2 contributes to inflammation via NF-κB activation,http://dx.doi.org/10.1080/21505594.2018.1536632,PMC7000202,30322331,CC BY,"Transmissible gastroenteritis virus (TGEV) infection causes acute enteritis in swine of all ages, and especially in suckling piglets. Small intestinal inflammation is considered a central event in the pathogenesis of TGEV infections, and nuclear factor-kappa B (NF-κB) is a key transcription factor in the inflammatory response. However, it is unclear whether NF-κB is crucial for inducing inflammation during a TGEV infection. Our results show that NF-κB was activated in swine testicular (ST) cells and intestinal epithelial cell lines J2 (IPEC-J2) cells infected with TGEV, which is consistent with the up-regulation of pro-inflammatory cytokines. Treatment of TGEV-infected ST cells and IPEC-J2 cells with the NF-κB-specific inhibitor caused the down-regulation of pro-inflammatory cytokine expression, but did not significantly affect TGEV replication. Individual TGEV protein screening results demonstrated that Nsp2 exhibited a high potential for activating NF-κB and enhancing the expression of pro-inflammatory cytokines. Functional domain analyzes indicated that the first 120 amino acid residues of Nsp2 were essential for NF-κB activation. Taken together, these data suggested that NF-κB activation was a major contributor to TGEV infection-induced inflammation, and that Nsp2 was the key viral protein involved in the regulation of inflammation, with amino acids 1–120 playing a critical role in activating NF-κB. Abbreviations: TCID50: 50% tissue culture infectious dose; DMEM: Dulbecco’s Modified Eagle Medium; eNOS: Endothelial nitric oxide synthase; FBS: fetal bovine serum; IFA: Indirect immunofluorescence; IκB: inhibitor of nuclear factor kappa-B; IL: interleukin; IPEC-J2: intestinal epithelial cell lines J2; IKK: IκB kinase; Luc: luciferase reporter gene; mAbs: monoclonal antibodies; MOI: multiple of infection; Nsp: nonstructural protein; NF-κB: nuclear factor-kappa ; ORFs: open reading frames; PBS: phosphate-buffered saline; p65 p-p65: phosphorylated; RT-PCR: reverse transcription PC; SeV: Sendai virus; ST: swine testicular; TGEV: Transmissible gastroenteritis virus; TNF-α: tumor necrosis factor α; UV-TGEV: Ultraviolet light-inactivated TGEV; ZnF: zinc finger",2018 Oct 29,"['Wang, Li', 'Qiao, Xinyuan', 'Zhang, Sijia', 'Qin, Yue', 'Guo, Tiantian', 'Hao, Zhenye', 'Sun, Li', 'Wang, Xiaona', 'Wang, Yanan', 'Jiang, Yanping', 'Tang, Lijie', 'Xu, Yigang', 'Li, Yijing']",Virulence,,,True
35b1d29a27113b46ea93b8cd542cb09a9da6a0c1,PMC,Detection methods for influenza A H1N1 virus with special reference to biosensors: a review,http://dx.doi.org/10.1042/BSR20193852,PMC7000365,32016385,CC BY,"H1N1 (Swine flu) is caused by influenza A virus, which is a member of Orthomyxoviridae family. Transmission of H1N1 occurs from human to human through air or sometimes from pigs to humans. The influenza virus has different RNA segments, which can reassert to make new virus strain with the possibility to create an outbreak in unimmunized people. Gene reassortment is a process through which new strains are emerging in pigs, as it has specific receptors for both human influenza and avian influenza viruses. H1N1 binds specifically with an α-2,6 glycosidic bond, which is present in human respiratory tract cells as well as in pigs. Considering the fact of fast multiplication of viruses inside the living cells, rapid detection methods need an hour. Currently, WHO recommended methods for the detection of swine flu include real-time PCR in specific testing centres that take 3–4 h. More recently, a number of methods such as Antigen–Antibody or RT-LAMP and DNA biosensors have also been developed that are rapid and more sensitive. This review describes the various challenges in the diagnosis of H1N1, and merits and demerits of conventional vis-à-vis latest methods with special emphasis on biosensors.",2020 Feb 4,"['Ravina,', 'Dalal, Anita', 'Mohan, Hari', 'Prasad, Minakshi', 'Pundir, C.S.']",Biosci Rep,,,True
38a33f302357e8dced322858ad61fe20b876d445,PMC,An assessment of Ebola-related stigma and its association with informal healthcare utilisation among Ebola survivors in Sierra Leone: a cross-sectional study,http://dx.doi.org/10.1186/s12889-020-8279-7,PMC7001224,32020858,CC BY,"BACKGROUND: We examined the magnitude and correlates of Ebola virus disease (EVD)-related stigma among EVD survivors in Sierra Leone since their return to their communities. In addition, we determined whether EVD-related stigma is a predictor of informal health care use among EVD survivors. METHODS: We conducted a cross-sectional study among 358 EVD survivors in five districts across all four geographic regions (Western Area, Northern Province, Eastern Province and Southern Province) of Sierra Leone. Ebola-related stigma was measured by adapting the validated HIV related stigma for people living with HIV/AIDS instrument. We also measured traditional and complementary medicine (T&CM) use (as a measure of informal healthcare use). Data were analysed using descriptive statistics and regression analysis. RESULTS: EVD survivors report higher levels of internalised stigma (0.92 ± 0.77) compared to total enacted stigma (0.71 ± 0.61). Social isolation (0.96 ± 0.88) was the highest reported enacted stigma subscale. Ebola survivors who identified as Christians [AOR = 2.51, 95%CI: 1.15–5.49, p = 0.021], who perceived their health to be fair/poor [AOR = 2.58, 95%CI: 1.39–4.77. p = 0.003] and who reside in the northern region of Sierra Leone [AOR = 2.80, 95%CI: 1.29–6.07, p = 0.009] were more likely to experience internalised stigma. Verbal abuse [AOR = 1.95, 95%CI: 1.09–3.49, p = 0.025] and healthcare neglect [AOR = 2.35, 95%CI: 1.37–4.02, p = 0.002] were independent predictors of T&CM use among EVD survivors. CONCLUSION: Our findings suggest EVD-related stigma (internalised and enacted) is prevalent among EVD survivors since their return to their communities. Religiosity, perceived health status and region were identified as independent predictors of internalised stigma. Verbal abuse and healthcare neglect predict informal healthcare use. EVD survivor-centred and community-driven anti-stigma programs are needed to promote EVD survivors’ recovery and community re-integration.",2020 Feb 5,"['James, Peter Bai', 'Wardle, Jonathan', 'Steel, Amie', 'Adams, Jon']",BMC Public Health,,,True
2765b43f0c431c63acf11a93ddb513f0332ca22b,PMC,"Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020",http://dx.doi.org/10.2807/1560-7917.ES.2020.25.4.2000058,PMC7001239,32019669,CC BY,"Since December 2019, China has been experiencing a large outbreak of a novel coronavirus (2019-nCoV) which can cause respiratory disease and severe pneumonia. We estimated the basic reproduction number R(0) of 2019-nCoV to be around 2.2 (90% high density interval: 1.4–3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and pandemic influenza, indicating a risk of global spread.",2020 Jan 30,"['Riou, Julien', 'Althaus, Christian L.']",Euro Surveill,,,True
9aa730b49e0c21575e0dd8ba78264cce5c0f2f0b,PMC,"Novel coronavirus (2019-nCoV) early-stage importation risk to Europe, January 2020",http://dx.doi.org/10.2807/1560-7917.ES.2020.25.4.2000057,PMC7001240,32019667,CC BY,"As at 27 January 2020, 42 novel coronavirus (2019-nCoV) cases were confirmed outside China. We estimate the risk of case importation to Europe from affected areas in China via air travel. We consider travel restrictions in place, three reported cases in France, one in Germany. Estimated risk in Europe remains high. The United Kingdom, Germany and France are at highest risk. Importation from Beijing and Shanghai would lead to higher and widespread risk for Europe.",2020 Jan 30,"['Pullano, Giulia', 'Pinotti, Francesco', 'Valdano, Eugenio', 'Boëlle, Pierre-Yves', 'Poletto, Chiara', 'Colizza, Vittoria']",Euro Surveill,,,False
82210c1cb5ac59acd1468cedcaf6fb8d951f4903,PMC,"Novel coronavirus (2019-nCoV) early-stage importation risk to Europe, January 2020",http://dx.doi.org/10.2807/1560-7917.ES.2020.25.4.2000057,PMC7001240,32019667,CC BY,"As at 27 January 2020, 42 novel coronavirus (2019-nCoV) cases were confirmed outside China. We estimate the risk of case importation to Europe from affected areas in China via air travel. We consider travel restrictions in place, three reported cases in France, one in Germany. Estimated risk in Europe remains high. The United Kingdom, Germany and France are at highest risk. Importation from Beijing and Shanghai would lead to higher and widespread risk for Europe.",2020 Jan 30,"['Pullano, Giulia', 'Pinotti, Francesco', 'Valdano, Eugenio', 'Boëlle, Pierre-Yves', 'Poletto, Chiara', 'Colizza, Vittoria']",Euro Surveill,,,True
ce0425b48e9b111a10f612fc562a2cd316633c15,PMC,Vaccines and Therapeutics Against Hantaviruses,http://dx.doi.org/10.3389/fmicb.2019.02989,PMC7002362,32082263,CC BY,"Hantaviruses (HVs) are rodent-transmitted viruses that can cause hantavirus cardiopulmonary syndrome (HCPS) in the Americas and hemorrhagic fever with renal syndrome (HFRS) in Eurasia. Together, these viruses have annually caused approximately 200,000 human infections worldwide in recent years, with a case fatality rate of 5–15% for HFRS and up to 40% for HCPS. There is currently no effective treatment available for either HFRS or HCPS. Only whole virus inactivated vaccines against HTNV or SEOV are licensed for use in the Republic of Korea and China, but the protective efficacies of these vaccines are uncertain. To a large extent, the immune correlates of protection against hantavirus are not known. In this review, we summarized the epidemiology, virology, and pathogenesis of four HFRS-causing viruses, HTNV, SEOV, PUUV, and DOBV, and two HCPS-causing viruses, ANDV and SNV, and then discussed the existing knowledge on vaccines and therapeutics against these diseases. We think that this information will shed light on the rational development of new vaccines and treatments.",2020 Jan 30,"['Liu, Rongrong', 'Ma, Hongwei', 'Shu, Jiayi', 'Zhang, Qiang', 'Han, Mingwei', 'Liu, Ziyu', 'Jin, Xia', 'Zhang, Fanglin', 'Wu, Xingan']",Front Microbiol,,,True
d5dc0143ba5f664b7bf724644a70a871388aaf38,PMC,Vaccines and Therapeutics Against Hantaviruses,http://dx.doi.org/10.3389/fmicb.2019.02989,PMC7002362,32082263,CC BY,"Hantaviruses (HVs) are rodent-transmitted viruses that can cause hantavirus cardiopulmonary syndrome (HCPS) in the Americas and hemorrhagic fever with renal syndrome (HFRS) in Eurasia. Together, these viruses have annually caused approximately 200,000 human infections worldwide in recent years, with a case fatality rate of 5–15% for HFRS and up to 40% for HCPS. There is currently no effective treatment available for either HFRS or HCPS. Only whole virus inactivated vaccines against HTNV or SEOV are licensed for use in the Republic of Korea and China, but the protective efficacies of these vaccines are uncertain. To a large extent, the immune correlates of protection against hantavirus are not known. In this review, we summarized the epidemiology, virology, and pathogenesis of four HFRS-causing viruses, HTNV, SEOV, PUUV, and DOBV, and two HCPS-causing viruses, ANDV and SNV, and then discussed the existing knowledge on vaccines and therapeutics against these diseases. We think that this information will shed light on the rational development of new vaccines and treatments.",2020 Jan 30,"['Liu, Rongrong', 'Ma, Hongwei', 'Shu, Jiayi', 'Zhang, Qiang', 'Han, Mingwei', 'Liu, Ziyu', 'Jin, Xia', 'Zhang, Fanglin', 'Wu, Xingan']",Front Microbiol,,,False
197489ce2e74e5566e1cd13fdce4a26b4eba45f6,PMC,Antiviral activity of iridoid glycosides extracted from Fructus Gardeniae against influenza A virus by PACT-dependent suppression of viral RNA replication,http://dx.doi.org/10.1038/s41598-020-58443-3,PMC7002373,32024921,CC BY,"Epidemic and pandemic influenza A virus (IAV) poses a significant threat to human populations worldwide. Iridoid glycosides are principal bioactive components from the Gardenia jasminoides J. Ellis fruit that exhibit antiviral activity against several strains of IAV. In the present study, we evaluated the protective effect of Fructus Gardeniae iridoid glycoside extracts (IGEs) against IAV by cytopathogenic effect(CPE), MTT and a plaque formation assay in vitro and examined the reduction in the pulmonary index (PI), restoration of body weight, reduction in mortality and increases in survival time in vivo. As a host factor, PACT provides protection against the pathogenic influenza A virus by interacting with IAV polymerase and activating the IFN-I response. To verify the whether IGEs suppress IAV replication in a PACT-dependent manner, IAV RNA replication, expression of PACT and the phosphorylation of eIF2α in A549 cells were detected; the levels of IFNβ, PACT and PKR in mouse lung tissues were determined; and the activity of IAV polymerase was evaluated in PACT-compromised cells. The results indicated that IGEs sufficiently alleviated cell damage and suppressed IAV replication in vitro, protecting mice from IAV-induced injury and lethal IAV infection. These anti-IAV effects might be related to disrupted interplay between IVA polymerase and PACT and/or prevention of a PACT-dependent overactivated IFN-I antiviral response. Taken together, our findings reveal a new facet of the mechanisms by which IGEs fight the influenza A virus in a PACT-dependent manner.",2020 Feb 5,"['Guo, Shanshan', 'Bao, Lei', 'Li, Chun', 'Sun, Jing', 'Zhao, Ronghua', 'Cui, Xiaolan']",Sci Rep,,,True
625afb5a588fd265e15b652a437ef9f521682aee,PMC,"Montelukast, an Anti-asthmatic Drug, Inhibits Zika Virus Infection by Disrupting Viral Integrity",http://dx.doi.org/10.3389/fmicb.2019.03079,PMC7002393,32082265,CC BY,"The association of Zika virus (ZIKV) infection and severe complications including neurological sequelae especially fetal microcephaly has aroused global attentions since its outbreak in 2015. Currently, there are no vaccines or therapeutic drugs clinically approved for treatments of ZIKV infection, however. And the drugs used for treating ZIKV in pregnant women require a higher safety profile. Here, we identified an anti-asthmatic drug, montelukast, which is of safety profile for pregnant women and exhibited antiviral efficacy against ZIKV infection in vitro and in vivo. And we showed that montelukast could disrupt the integrity of the virions to release the viral genomic RNA, hence irreversibly inhibiting viral infectivity. In consideration of the neuro-protective activity that montelukast possessed, which was previously reported, it is promising that montelukast could be used for patients with ZIKV infection, particularly for pregnant women.",2020 Jan 30,"['Chen, Yongkang', 'Li, Yuan', 'Wang, Xiaohuan', 'Zou, Peng']",Front Microbiol,,,True
fd28e6d03eef27b0454f13ca539dc1498242a4c2,PMC,A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version),http://dx.doi.org/10.1186/s40779-020-0233-6,PMC7003341,32029004,CC BY,"In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named “2019 novel coronavirus (2019-nCoV)” by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.",2020 Feb 6,"['Jin, Ying-Hui', 'Cai, Lin', 'Cheng, Zhen-Shun', 'Cheng, Hong', 'Deng, Tong', 'Fan, Yi-Pin', 'Fang, Cheng', 'Huang, Di', 'Huang, Lu-Qi', 'Huang, Qiao', 'Han, Yong', 'Hu, Bo', 'Hu, Fen', 'Li, Bing-Hui', 'Li, Yi-Rong', 'Liang, Ke', 'Lin, Li-Kai', 'Luo, Li-Sha', 'Ma, Jing', 'Ma, Lin-Lu', 'Peng, Zhi-Yong', 'Pan, Yun-Bao', 'Pan, Zhen-Yu', 'Ren, Xue-Qun', 'Sun, Hui-Min', 'Wang, Ying', 'Wang, Yun-Yun', 'Weng, Hong', 'Wei, Chao-Jie', 'Wu, Dong-Fang', 'Xia, Jian', 'Xiong, Yong', 'Xu, Hai-Bo', 'Yao, Xiao-Mei', 'Yuan, Yu-Feng', 'Ye, Tai-Sheng', 'Zhang, Xiao-Chun', 'Zhang, Ying-Wen', 'Zhang, Yin-Gao', 'Zhang, Hua-Min', 'Zhao, Yan', 'Zhao, Ming-Juan', 'Zi, Hao', 'Zeng, Xian-Tao', 'Wang, Yong-Yan', 'Wang, Xing-Huan', None]",Mil Med Res,,,True
c68a6448007a158321fd4b610a17e646d77fea95,PMC,Post-pandemic influenza A/H1N1pdm09 is associated with more severe outcomes than A/H3N2 and other respiratory viruses in adult hospitalisations,http://dx.doi.org/10.1017/S095026881900195X,PMC7003621,31775940,CC BY,"This study compares the frequency and severity of influenza A/H1N1pdm09 (A/H1), influenza A/H3N2 (A/H3) and other respiratory virus infections in hospitalised patients. Data from 17 332 adult hospitalised patients admitted to Sir Charles Gairdner Hospital, Perth, Western Australia, with a respiratory illness between 2012 and 2015 were linked with data containing reverse transcription polymerase chain reaction results for respiratory viruses including A/H1, A/H3, influenza B, human metapneumovirus, respiratory syncytial virus and parainfluenza. Of these, 1753 (10.1%) had test results. Multivariable regression analyses were conducted to compare the viruses for clinical outcomes including ICU admission, ventilation, pneumonia, length of stay and death. Patients with A/H1 were more likely to experience severe outcomes such as ICU admission (OR 2.5, 95% CI 1.2–5.5, P = 0.016), pneumonia (OR 3.0, 95% CI 1.6–5.7, P < 0.001) and lower risk of discharge from hospital (indicating longer lengths of hospitalisation; HR 0.64 95% CI 0.47–0.88, P = 0.005), than patients with A/H3. Patients with a non-influenza respiratory virus were less likely to experience severe clinical outcomes than patients with A/H1, however, had similar likelihood when compared to patients with A/H3. Patients hospitalised with A/H1 had higher odds of severe outcomes than patients with A/H3 or other respiratory viruses. Knowledge of circulating influenza strains is important for healthcare preparedness.",,"['Minney-Smith, C. A.', 'Selvey, L. A.', 'Levy, A.', 'Smith, D. W.']",Epidemiol Infect.; 147:e310,,,True
c2a69ec62b5553d158b04c9a91409e451f91e2ee,PMC,Demographic and environmental drivers of metagenomic viral diversity in vampire bats,http://dx.doi.org/10.1111/mec.15250,PMC7004108,31561274,CC BY,"Viruses infect all forms of life and play critical roles as agents of disease, drivers of biochemical cycles and sources of genetic diversity for their hosts. Our understanding of viral diversity derives primarily from comparisons among host species, precluding insight into how intraspecific variation in host ecology affects viral communities or how predictable viral communities are across populations. Here we test spatial, demographic and environmental hypotheses explaining viral richness and community composition across populations of common vampire bats, which occur in diverse habitats of North, Central and South America. We demonstrate marked variation in viral communities that was not consistently predicted by a null model of declining community similarity with increasing spatial or genetic distances separating populations. We also find no evidence that larger bat colonies host greater viral diversity. Instead, viral diversity follows an elevational gradient, is enriched by juvenile‐biased age structure, and declines with local anthropogenic food resources as measured by livestock density. Our results establish the value of linking the modern influx of metagenomic sequence data with comparative ecology, reveal that snapshot views of viral diversity are unlikely to be representative at the species level, and affirm existing ecological theories that link host ecology not only to single pathogen dynamics but also to viral communities.",2020 Jan 23,"['Bergner, Laura M.', 'Orton, Richard J.', 'Benavides, Julio A.', 'Becker, Daniel J.', 'Tello, Carlos', 'Biek, Roman', 'Streicker, Daniel G.']",Mol Ecol,,,True
8ca98b59fa6bb5b1d4dfdb0b89cfcdbcaa1a0474,PMC,Demographic and environmental drivers of metagenomic viral diversity in vampire bats,http://dx.doi.org/10.1111/mec.15250,PMC7004108,31561274,CC BY,"Viruses infect all forms of life and play critical roles as agents of disease, drivers of biochemical cycles and sources of genetic diversity for their hosts. Our understanding of viral diversity derives primarily from comparisons among host species, precluding insight into how intraspecific variation in host ecology affects viral communities or how predictable viral communities are across populations. Here we test spatial, demographic and environmental hypotheses explaining viral richness and community composition across populations of common vampire bats, which occur in diverse habitats of North, Central and South America. We demonstrate marked variation in viral communities that was not consistently predicted by a null model of declining community similarity with increasing spatial or genetic distances separating populations. We also find no evidence that larger bat colonies host greater viral diversity. Instead, viral diversity follows an elevational gradient, is enriched by juvenile‐biased age structure, and declines with local anthropogenic food resources as measured by livestock density. Our results establish the value of linking the modern influx of metagenomic sequence data with comparative ecology, reveal that snapshot views of viral diversity are unlikely to be representative at the species level, and affirm existing ecological theories that link host ecology not only to single pathogen dynamics but also to viral communities.",2020 Jan 23,"['Bergner, Laura M.', 'Orton, Richard J.', 'Benavides, Julio A.', 'Becker, Daniel J.', 'Tello, Carlos', 'Biek, Roman', 'Streicker, Daniel G.']",Mol Ecol,,,True
ce1f762e478087400412172f30e184d92f17d976,PMC,"Prevalence and contribution of respiratory viruses in the community to rates of emergency department visits and hospitalizations with respiratory tract infections, chronic obstructive pulmonary disease and asthma",http://dx.doi.org/10.1371/journal.pone.0228544,PMC7004370,32027687,CC BY,"BACKGROUND: The individual and combined contribution of viral prevalence in the community to Emergency Department (ED) visits and hospitalizations with respiratory tract infections (RTIs), chronic obstructive pulmonary disease (COPD) and asthma is unclear. METHODS: A retrospective analysis on daily viral positive tests and daily ED visits and hospitalizations between 01/01/2003 to 31/12/2013 in Ontario, Canada. Viral data was collected from the Centre for Immunization and Respiratory Infectious Diseases (CIRID). The Canadian Institute for Health Information reports daily ED visits and hospitalizations for RTIs, COPD and asthma as a primary diagnosis. RESULTS: There were 4,365,578 ED visits with RTIs of which 321,719 (7.4%) were admitted to hospital; 817,141 ED visits for COPD of which 260,665 (31.9%) were admitted and 649,666 ED visits with asthma of which 68,626 (10.6%) were admitted. The percentage of positive tests to influenza A and B, respiratory syncytial virus (RSV), parainfluenza and adenovirus prevalence explained 57.4% of ED visits and 63.8% of hospitalizations for RTI, 41.4% of ED visits and 39.2% of hospitalizations with COPD but only 1.5% of ED visits and 2.7% of hospitalizations for asthma. The further addition of human metapneumovirus, rhinovirus and coronavirus over the final 3 years accounted for 66.7% of ED visits and 74.4% of hospitalizations for RTI, 52.5% of visits and 48.2% of hospitalizations for COPD, and only 13.3% of visits and 10.4% of hospitalizations for asthma. CONCLUSIONS: Community respiratory viral epidemics are major drivers of ED visits and hospitalizations with RTIs and COPD but only a modest contributor to asthma.",2020 Feb 6,"['Satia, Imran', 'Cusack, Ruth', 'Greene, Justina M.', 'O’Byrne, Paul M.', 'Killian, Kieran J.', 'Johnston, Neil']",PLoS One,,,True
4363936c1edadc4d1a30103f0dba198354b16051,PMC,Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak,http://dx.doi.org/10.1371/journal.ppat.1007857,PMC7004387,31961906,CC0,"The 2014–2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.",2020 Jan 21,"['Hicks, Joseph T.', 'Lee, Dong-Hun', 'Duvvuri, Venkata R.', 'Kim Torchetti, Mia', 'Swayne, David E.', 'Bahl, Justin']",PLoS Pathog,,,True
ef061b26a6059c2fbd7f00a6420c1b0a40b06202,PMC,Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak,http://dx.doi.org/10.1371/journal.ppat.1007857,PMC7004387,31961906,CC0,"The 2014–2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.",2020 Jan 21,"['Hicks, Joseph T.', 'Lee, Dong-Hun', 'Duvvuri, Venkata R.', 'Kim Torchetti, Mia', 'Swayne, David E.', 'Bahl, Justin']",PLoS Pathog,,,False
1ca0276492c516404664c6c718195cdc7d31c800,PMC,Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak,http://dx.doi.org/10.1371/journal.ppat.1007857,PMC7004387,31961906,CC0,"The 2014–2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.",2020 Jan 21,"['Hicks, Joseph T.', 'Lee, Dong-Hun', 'Duvvuri, Venkata R.', 'Kim Torchetti, Mia', 'Swayne, David E.', 'Bahl, Justin']",PLoS Pathog,,,False
d6bdd3e49b6d7050c1cd9b64214b11dc174527ac,PMC,Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak,http://dx.doi.org/10.1371/journal.ppat.1007857,PMC7004387,31961906,CC0,"The 2014–2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.",2020 Jan 21,"['Hicks, Joseph T.', 'Lee, Dong-Hun', 'Duvvuri, Venkata R.', 'Kim Torchetti, Mia', 'Swayne, David E.', 'Bahl, Justin']",PLoS Pathog,,,False
59945839e23a19be0c95eff73d2661a03624fc00,PMC,Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak,http://dx.doi.org/10.1371/journal.ppat.1007857,PMC7004387,31961906,CC0,"The 2014–2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.",2020 Jan 21,"['Hicks, Joseph T.', 'Lee, Dong-Hun', 'Duvvuri, Venkata R.', 'Kim Torchetti, Mia', 'Swayne, David E.', 'Bahl, Justin']",PLoS Pathog,,,False
a27bb62007adc991189dbf5992e9e0b660053bbb,PMC,Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak,http://dx.doi.org/10.1371/journal.ppat.1007857,PMC7004387,31961906,CC0,"The 2014–2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.",2020 Jan 21,"['Hicks, Joseph T.', 'Lee, Dong-Hun', 'Duvvuri, Venkata R.', 'Kim Torchetti, Mia', 'Swayne, David E.', 'Bahl, Justin']",PLoS Pathog,,,False
c5431ac3894d3a99a30cba37d58b42b38ee7dc65,PMC,Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak,http://dx.doi.org/10.1371/journal.ppat.1007857,PMC7004387,31961906,CC0,"The 2014–2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.",2020 Jan 21,"['Hicks, Joseph T.', 'Lee, Dong-Hun', 'Duvvuri, Venkata R.', 'Kim Torchetti, Mia', 'Swayne, David E.', 'Bahl, Justin']",PLoS Pathog,,,False
a50e01474c7fd48a938089de57f4ad1c7eaa3c1b,PMC,Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak,http://dx.doi.org/10.1371/journal.ppat.1007857,PMC7004387,31961906,CC0,"The 2014–2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.",2020 Jan 21,"['Hicks, Joseph T.', 'Lee, Dong-Hun', 'Duvvuri, Venkata R.', 'Kim Torchetti, Mia', 'Swayne, David E.', 'Bahl, Justin']",PLoS Pathog,,,False
bef454b49d54f26b538864e0237b8f1decbf6332,PMC,Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak,http://dx.doi.org/10.1371/journal.ppat.1007857,PMC7004387,31961906,CC0,"The 2014–2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.",2020 Jan 21,"['Hicks, Joseph T.', 'Lee, Dong-Hun', 'Duvvuri, Venkata R.', 'Kim Torchetti, Mia', 'Swayne, David E.', 'Bahl, Justin']",PLoS Pathog,,,False
1dff39968860a38ee90be26083d801c89ec03ee0,PMC,Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak,http://dx.doi.org/10.1371/journal.ppat.1007857,PMC7004387,31961906,CC0,"The 2014–2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.",2020 Jan 21,"['Hicks, Joseph T.', 'Lee, Dong-Hun', 'Duvvuri, Venkata R.', 'Kim Torchetti, Mia', 'Swayne, David E.', 'Bahl, Justin']",PLoS Pathog,,,False
c8286cc847f9e31a666396cd93f2340753f1ee9f,PMC,Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak,http://dx.doi.org/10.1371/journal.ppat.1007857,PMC7004387,31961906,CC0,"The 2014–2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.",2020 Jan 21,"['Hicks, Joseph T.', 'Lee, Dong-Hun', 'Duvvuri, Venkata R.', 'Kim Torchetti, Mia', 'Swayne, David E.', 'Bahl, Justin']",PLoS Pathog,,,False
621018c6157fb170708e7279c6c6409680e31e94,PMC,Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak,http://dx.doi.org/10.1371/journal.ppat.1007857,PMC7004387,31961906,CC0,"The 2014–2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.",2020 Jan 21,"['Hicks, Joseph T.', 'Lee, Dong-Hun', 'Duvvuri, Venkata R.', 'Kim Torchetti, Mia', 'Swayne, David E.', 'Bahl, Justin']",PLoS Pathog,,,False
eff23011e9eb52a3406db4f052516f6d2639fd82,PMC,Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak,http://dx.doi.org/10.1371/journal.ppat.1007857,PMC7004387,31961906,CC0,"The 2014–2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.",2020 Jan 21,"['Hicks, Joseph T.', 'Lee, Dong-Hun', 'Duvvuri, Venkata R.', 'Kim Torchetti, Mia', 'Swayne, David E.', 'Bahl, Justin']",PLoS Pathog,,,False
87bbb6419983d5bb2d15c56684df2044d900cb63,PMC,Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak,http://dx.doi.org/10.1371/journal.ppat.1007857,PMC7004387,31961906,CC0,"The 2014–2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.",2020 Jan 21,"['Hicks, Joseph T.', 'Lee, Dong-Hun', 'Duvvuri, Venkata R.', 'Kim Torchetti, Mia', 'Swayne, David E.', 'Bahl, Justin']",PLoS Pathog,,,False
0116d6ee49c69bb175b8de793826606dc82f9e78,PMC,Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak,http://dx.doi.org/10.1371/journal.ppat.1007857,PMC7004387,31961906,CC0,"The 2014–2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.",2020 Jan 21,"['Hicks, Joseph T.', 'Lee, Dong-Hun', 'Duvvuri, Venkata R.', 'Kim Torchetti, Mia', 'Swayne, David E.', 'Bahl, Justin']",PLoS Pathog,,,False
11f13e2859eb22b349dbef68fd8124b8ba445aac,PMC,"Initial Public Health Response and Interim Clinical Guidance for the 2019 Novel Coronavirus Outbreak — United States, December 31, 2019–February 4, 2020",http://dx.doi.org/10.15585/mmwr.mm6905e1,PMC7004396,32027631,CC BY,,2020 Feb 7,"['Patel, Anita', 'Jernigan, Daniel B.', None, None, None, 'Abdirizak, Fatuma', 'Abedi, Glen', 'Aggarwal, Sharad', 'Albina, Denise', 'Allen, Elizabeth', 'Andersen, Lauren', 'Anderson, Jade', 'Anderson, Megan', 'Anderson, Tara', 'Anderson, Kayla', 'Bardossy, Ana Cecilia', 'Barry, Vaughn', 'Beer, Karlyn', 'Bell, Michael', 'Berger, Sherri', 'Bertulfo, Joseph', 'Biggs, Holly', 'Bornemann, Jennifer', 'Bornstein, Josh', 'Bower, Willie', 'Bresee, Joseph', 'Brown, Clive', 'Budd, Alicia', 'Buigut, Jennifer', 'Burke, Stephen', 'Burke, Rachel', 'Burns, Erin', 'Butler, Jay', 'Cantrell, Russell', 'Cardemil, Cristina', 'Cates, Jordan', 'Cetron, Marty', 'Chatham-Stephens, Kevin', 'Chatham-Stevens, Kevin', 'Chea, Nora', 'Christensen, Bryan', 'Chu, Victoria', 'Clarke, Kevin', 'Cleveland, Angela', 'Cohen, Nicole', 'Cohen, Max', 'Cohn, Amanda', 'Collins, Jennifer', 'Dahl, Rebecca', 'Daley, Walter', 'Dasari, Vishal', 'Davlantes, Elizabeth', 'Dawson, Patrick', 'Delaney, Lisa', 'Donahue, Matthew', 'Dowell, Chad', 'Dyal, Jonathan', 'Edens, William', 'Eidex, Rachel', 'Epstein, Lauren', 'Evans, Mary', 'Fagan, Ryan', 'Farris, Kevin', 'Feldstein, Leora', 'Fox, LeAnne', 'Frank, Mark', 'Freeman, Brandi', 'Fry, Alicia', 'Fuller, James', 'Galang, Romeo', 'Gerber, Sue', 'Gokhale, Runa', 'Goldstein, Sue', 'Gorman, Sue', 'Gregg, William', 'Greim, William', 'Grube, Steven', 'Hall, Aron', 'Haynes, Amber', 'Hill, Sherrasa', 'Hornsby-Myers, Jennifer', 'Hunter, Jennifer', 'Ionta, Christopher', 'Isenhour, Cheryl', 'Jacobs, Max', 'Slifka, Kara Jacobs', 'Jernigan, Daniel', 'Jhung, Michael', 'Jones-Wormley, Jamie', 'Kambhampati, Anita', 'Kamili, Shifaq', 'Kennedy, Pamela', 'Kent, Charlotte', 'Killerby, Marie', 'Kim, Lindsay', 'Kirking, Hannah', 'Koonin, Lisa', 'Koppaka, Ram', 'Kosmos, Christine', 'Kuhar, David', 'Kuhnert-Tallman, Wendi', 'Kujawski, Stephanie', 'Kumar, Archana', 'Landon, Alexander', 'Lee, Leslie', 'Leung, Jessica', 'Lindstrom, Stephen', 'Link-Gelles, Ruth', 'Lively, Joana', 'Lu, Xiaoyan', 'Lynch, Brian', 'Malapati, Lakshmi', 'Mandel, Samantha', 'Manns, Brian', 'Marano, Nina', 'Marlow, Mariel', 'Marston, Barbara', 'McClung, Nancy', 'McClure, Liz', 'McDonald, Emily', 'McGovern, Oliva', 'Messonnier, Nancy', 'Midgley, Claire', 'Moulia, Danielle', 'Murray, Janna', 'Noelte, Kate', 'Noonan-Smith, Michelle', 'Nordlund, Kristen', 'Norton, Emily', 'Oliver, Sara', 'Pallansch, Mark', 'Parashar, Umesh', 'Patel, Anita', 'Patel, Manisha', 'Pettrone, Kristen', 'Pierce, Taran', 'Pietz, Harald', 'Pillai, Satish', 'Radonovich, Lewis', 'Reagan-Steiner, Sarah', 'Reel, Amy', 'Reese, Heather', 'Rha, Brian', 'Ricks, Philip', 'Rolfes, Melissa', 'Roohi, Shahrokh', 'Roper, Lauren', 'Rotz, Lisa', 'Routh, Janell', 'Sakthivel, Senthil Kumar', 'Sarmiento, Luisa', 'Schindelar, Jessica', 'Schneider, Eileen', 'Schuchat, Anne', 'Scott, Sarah', 'Shetty, Varun', 'Shockey, Caitlin', 'Shugart, Jill', 'Stenger, Mark', 'Stuckey, Matthew', 'Sunshine, Brittany', 'Sykes, Tamara', 'Trapp, Jonathan', 'Uyeki, Timothy', 'Vahey, Grace', 'Valderrama, Amy', 'Villanueva, Julie', 'Walker, Tunicia', 'Wallace, Megan', 'Wang, Lijuan', 'Watson, John', 'Weber, Angie', 'Weinbaum, Cindy', 'Weldon, William', 'Westnedge, Caroline', 'Whitaker, Brett', 'Whitaker, Michael', 'Williams, Alcia', 'Williams, Holly', 'Willams, Ian', 'Wong, Karen', 'Xie, Amy', 'Yousef, Anna']",MMWR Morb Mortal Wkly Rep,,,True
6807bdafe0aadb07814a155a43e4205e0246a2e4,PMC,Insights Into the Role of Endoplasmic Reticulum Stress in Infectious Diseases,http://dx.doi.org/10.3389/fimmu.2019.03147,PMC7005066,32082307,CC BY,"The endoplasmic reticulum (ER) is the major organelle in the cell for protein folding and plays an important role in cellular functions. The unfolded protein response (UPR) is activated in response to misfolded or unfolded protein accumulation in the ER. However, the UPR successfully alleviates the ER stress. If UPR fails to restore ER homeostasis, apoptosis is induced. ER stress plays an important role in innate immune signaling in response to microorganisms. Dysregulation of UPR signaling contributes to the pathogenesis of a variety of infectious diseases. In this review, we summarize the contribution of ER stress to the innate immune response to invading microorganisms and its role in the pathogenesis of infectious diseases.",2020 Jan 31,"['Choi, Ji-Ae', 'Song, Chang-Hwa']",Front Immunol,,,True
0c917c3becd5b37cc4e44ad2c822ba132d339728,PMC,Targeting cancer stem cell pathways for cancer therapy,http://dx.doi.org/10.1038/s41392-020-0110-5,PMC7005297,32047658,CC BY,"Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.",2020 Feb 7,"['Yang, Liqun', 'Shi, Pengfei', 'Zhao, Gaichao', 'Xu, Jie', 'Peng, Wen', 'Zhang, Jiayi', 'Zhang, Guanghui', 'Wang, Xiaowen', 'Dong, Zhen', 'Chen, Fei', 'Cui, Hongjuan']",Signal Transduct Target Ther,,,True
9d3e94d800e4c0263d01a9ceed3cc7b6af5a7478,PMC,Ebola virus disease outbreak in Korea: use of a mathematical model and stochastic simulation to estimate risk,http://dx.doi.org/10.4178/epih.e2019048,PMC7005456,31801320,CC BY,"OBJECTIVES: According to the World Health Organization, there have been frequent reports of Ebola virus disease (EVD) since the 2014 EVD pandemic in West Africa. We aim to estimate the outbreak scale when an EVD infected person arrives in Korea. METHODS: Western Africa EVD epidemic mathematical model SEIJR or SEIJQR was modified to create a Korean EVD outbreak model. The expected number of EVD patients and outbreak duration were calculated by stochastic simulation under the scenarios of Best case, Diagnosis delay, and Case missing. RESULTS: The 2,000 trials of stochastic simulation for each scenario demonstrated the following results: The possible median number of patients is 2 and the estimated maximum number is 11 when the government intervention is proceeded immediately right after the first EVD case is confirmed. With a 6-day delay in diagnosis of the first case, the median number of patients becomes 7, and the maximum, 20. If the first case is missed and the government intervention is not activated until 2 cases of secondary infection occur, the median number of patients is estimated at 15, and the maximum, at 35. CONCLUSIONS: Timely and rigorous diagnosis is important to reduce the spreading scale of infection when a new communicable disease is inflowed into Korea. Moreover, it is imperative to strengthen the local surveillance system and diagnostic protocols to avoid missing cases of secondary infection.",2019 Nov 24,"['Ko, Youngsuk', 'Lee, Seok-Min', 'Kim, Soyoung', 'Ki, Moran', 'Jung, Eunok']",Epidemiol Health,,,True
a05a9d684b2b6de28b18e78a82585b76a973e258,PMC,Ebola virus disease outbreak in Korea: use of a mathematical model and stochastic simulation to estimate risk,http://dx.doi.org/10.4178/epih.e2019048,PMC7005456,31801320,CC BY,"OBJECTIVES: According to the World Health Organization, there have been frequent reports of Ebola virus disease (EVD) since the 2014 EVD pandemic in West Africa. We aim to estimate the outbreak scale when an EVD infected person arrives in Korea. METHODS: Western Africa EVD epidemic mathematical model SEIJR or SEIJQR was modified to create a Korean EVD outbreak model. The expected number of EVD patients and outbreak duration were calculated by stochastic simulation under the scenarios of Best case, Diagnosis delay, and Case missing. RESULTS: The 2,000 trials of stochastic simulation for each scenario demonstrated the following results: The possible median number of patients is 2 and the estimated maximum number is 11 when the government intervention is proceeded immediately right after the first EVD case is confirmed. With a 6-day delay in diagnosis of the first case, the median number of patients becomes 7, and the maximum, 20. If the first case is missed and the government intervention is not activated until 2 cases of secondary infection occur, the median number of patients is estimated at 15, and the maximum, at 35. CONCLUSIONS: Timely and rigorous diagnosis is important to reduce the spreading scale of infection when a new communicable disease is inflowed into Korea. Moreover, it is imperative to strengthen the local surveillance system and diagnostic protocols to avoid missing cases of secondary infection.",2019 Nov 24,"['Ko, Youngsuk', 'Lee, Seok-Min', 'Kim, Soyoung', 'Ki, Moran', 'Jung, Eunok']",Epidemiol Health,,,True
d77d46a447e665ddfcc2fe9a89a28b83f3050c5b,PMC,Ebola virus disease outbreak in Korea: use of a mathematical model and stochastic simulation to estimate risk,http://dx.doi.org/10.4178/epih.e2019048,PMC7005456,31801320,CC BY,"OBJECTIVES: According to the World Health Organization, there have been frequent reports of Ebola virus disease (EVD) since the 2014 EVD pandemic in West Africa. We aim to estimate the outbreak scale when an EVD infected person arrives in Korea. METHODS: Western Africa EVD epidemic mathematical model SEIJR or SEIJQR was modified to create a Korean EVD outbreak model. The expected number of EVD patients and outbreak duration were calculated by stochastic simulation under the scenarios of Best case, Diagnosis delay, and Case missing. RESULTS: The 2,000 trials of stochastic simulation for each scenario demonstrated the following results: The possible median number of patients is 2 and the estimated maximum number is 11 when the government intervention is proceeded immediately right after the first EVD case is confirmed. With a 6-day delay in diagnosis of the first case, the median number of patients becomes 7, and the maximum, 20. If the first case is missed and the government intervention is not activated until 2 cases of secondary infection occur, the median number of patients is estimated at 15, and the maximum, at 35. CONCLUSIONS: Timely and rigorous diagnosis is important to reduce the spreading scale of infection when a new communicable disease is inflowed into Korea. Moreover, it is imperative to strengthen the local surveillance system and diagnostic protocols to avoid missing cases of secondary infection.",2019 Nov 24,"['Ko, Youngsuk', 'Lee, Seok-Min', 'Kim, Soyoung', 'Ki, Moran', 'Jung, Eunok']",Epidemiol Health,,,True
be5d1a017f86407c335f5c76eb69b85d3b81c110,PMC,Causes of fever in Gabonese children: a cross-sectional hospital-based study,http://dx.doi.org/10.1038/s41598-020-58204-2,PMC7005879,32034188,CC BY,"The causes of infections in pediatric populations differ between age groups and settings, particularly in the tropics. Such differences in epidemiology may lead to misdiagnosis and ineffective empirical treatment. Here, we investigated the current spectrum of pathogens causing febrile diseases leading to pediatric hospitalization in Lambaréné, Gabon. From August 2015 to March 2016, we conducted a prospective, cross-sectional, hospital-based study in a provincial hospital. Patients were children ≤ 15 years with fever ≥ 38 °C and required hospitalization. A total of 600 febrile patients were enrolled. Malaria was the main diagnosis found in 52% (311/600) patients. Blood cultures revealed septicemia in 3% (17/593), among them four cases of typhoid fever. The other causes of fever were heterogeneously distributed between both bacteria and viruses. Severe infections identified by Lambaréné Organ Dysfunction Score (LODS) were also most often caused by malaria, but children with danger signs did not have more coinfections than others. In 6% (35/600) of patients, no pathogen was isolated. In Gabon, malaria is still the major cause of fever in children, followed by a bacterial and viral disease. Guidelines for both diagnosis and management should be tailored to the spectrum of pathogens and resources available locally.",2020 Feb 7,"['Fernandes, José Francisco', 'Held, Jana', 'Dorn, Magdalena', 'Lalremruata, Albert', 'Schaumburg, Frieder', 'Alabi, Abraham', 'Agbanrin, Maradona Daouda', 'Kokou, Cosme', 'Ben Adande, Abel', 'Esen, Meral', 'Eibach, Daniel', 'Adegnika, Ayola Akim', 'Agnandji, Sélidji Todagbé', 'Lell, Bertrand', 'Eckerle, Isabella', 'Henrichfreise, Beate', 'Hogan, Benedikt', 'May, Jürgen', 'Kremsner, Peter Gottfried', 'Grobusch, Martin Peter', 'Mordmüller, Benjamin']",Sci Rep,,,True
03ae4b61aa2d9641f38287806612fc16f58d4299,PMC,Causes of fever in Gabonese children: a cross-sectional hospital-based study,http://dx.doi.org/10.1038/s41598-020-58204-2,PMC7005879,32034188,CC BY,"The causes of infections in pediatric populations differ between age groups and settings, particularly in the tropics. Such differences in epidemiology may lead to misdiagnosis and ineffective empirical treatment. Here, we investigated the current spectrum of pathogens causing febrile diseases leading to pediatric hospitalization in Lambaréné, Gabon. From August 2015 to March 2016, we conducted a prospective, cross-sectional, hospital-based study in a provincial hospital. Patients were children ≤ 15 years with fever ≥ 38 °C and required hospitalization. A total of 600 febrile patients were enrolled. Malaria was the main diagnosis found in 52% (311/600) patients. Blood cultures revealed septicemia in 3% (17/593), among them four cases of typhoid fever. The other causes of fever were heterogeneously distributed between both bacteria and viruses. Severe infections identified by Lambaréné Organ Dysfunction Score (LODS) were also most often caused by malaria, but children with danger signs did not have more coinfections than others. In 6% (35/600) of patients, no pathogen was isolated. In Gabon, malaria is still the major cause of fever in children, followed by a bacterial and viral disease. Guidelines for both diagnosis and management should be tailored to the spectrum of pathogens and resources available locally.",2020 Feb 7,"['Fernandes, José Francisco', 'Held, Jana', 'Dorn, Magdalena', 'Lalremruata, Albert', 'Schaumburg, Frieder', 'Alabi, Abraham', 'Agbanrin, Maradona Daouda', 'Kokou, Cosme', 'Ben Adande, Abel', 'Esen, Meral', 'Eibach, Daniel', 'Adegnika, Ayola Akim', 'Agnandji, Sélidji Todagbé', 'Lell, Bertrand', 'Eckerle, Isabella', 'Henrichfreise, Beate', 'Hogan, Benedikt', 'May, Jürgen', 'Kremsner, Peter Gottfried', 'Grobusch, Martin Peter', 'Mordmüller, Benjamin']",Sci Rep,,,True
5b31a92b9c0bbc361c12fb2c00bcb17ff3fab61c,PMC,Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1080/22221751.2020.1713705,PMC7006675,31964246,CC BY,"Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) causes a severe respiratory disease in humans. The MERS-CoV spike (S) glycoprotein mediates viral entry into target cells. For this, MERS-CoV S engages the host cell protein dipeptidyl peptidase 4 (DPP4, CD26) and the interface between MERS-CoV S and DPP4 has been resolved on the atomic level. Here, we asked whether naturally-occurring polymorphisms in DPP4, that alter amino acid residues required for MERS-CoV S binding, influence cellular entry of MERS-CoV. By screening of public databases, we identified fourteen such polymorphisms. Introduction of the respective mutations into DPP4 revealed that all except one (Δ346-348) were compatible with robust DPP4 expression. Four polymorphisms (K267E, K267N, A291P and Δ346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. Two polymorphisms (K267E and A291P) were analyzed in the context of authentic MERS-CoV and were found to attenuate viral replication. Collectively, we identified naturally-occurring polymorphisms in DPP4 that negatively impact cellular entry of MERS-CoV and might thus modulate MERS development in infected patients.",2020 Jan 21,"['Kleine-Weber, Hannah', 'Schroeder, Simon', 'Krüger, Nadine', 'Prokscha, Alexander', 'Naim, Hassan Y.', 'Müller, Marcel A.', 'Drosten, Christian', 'Pöhlmann, Stefan', 'Hoffmann, Markus']",Emerg Microbes Infect,,,True
3cc1733c40062f59a5d1e9c7c9fd318c8041c0a2,PMC,Prevalence of Group A Streptococcus in Primary Care Patients and the Utility of C-Reactive Protein and Clinical Scores for Its Identification in Thailand,http://dx.doi.org/10.4269/ajtmh.19-0502,PMC7008346,31889507,CC BY,"Pharyngitis is usually caused by a viral infection for which antibiotics are often unnecessarily prescribed, adding to the burden of antimicrobial resistance. Identifying who needs antibiotics is challenging; microbiological confirmation and clinical scores are used but have limitations. In a cross-sectional study nested within a randomized controlled trial, we estimated the prevalence and antibiotic susceptibility profiles of group A Streptococcus (GAS) in patients presenting to primary care with a sore throat and fever in northern Thailand. We then evaluated the use of C-reactive protein (CRP) and clinical scores (Centor and FeverPAIN) to identify the presence of GAS. One hundred sixty-nine patients were enrolled, of whom 35 (20.7%) had β-hemolytic Streptococci (BHS) isolated from throat swab culture, and 11 (6.5%) had GAS. All GAS isolates were sensitive to penicillin G. The median CRP of those without BHS isolation was 10 mg/L (interquartile range [IQR] ≤ 8–18), compared with 18 mg/L (IQR 9–71, P = 0.0302) for those with GAS and 14 mg/L (IQR ≤ 8–38, P = 0.0516) for those with any BHS isolated. However, there were no significant relationships between CRP > 8 mg/L (P = 0.112), Centor ≥ 3 (P = 0.212), and FeverPAIN ≥ 4 (P = 1.000), and the diagnosis of GAS compared with no BHS isolation. Identifying who requires antibiotics for pharyngitis remains challenging and necessitates further larger studies. C-reactive protein testing alone, although imperfect, can reduce prescribing compared with routine care. Targeted CRP testing through clinical scoring may be the most cost-effective approach to ruling out GAS infection.",2020 Feb 30,"['Greer, Rachel', 'Althaus, Thomas', 'Ling, Clare', 'Intralawan, Daranee', 'Nedsuwan, Supalert', 'Thaipadungpanit, Janjira', 'Wangrangsimakul, Tri', 'Butler, Christopher', 'Day, Nicolas', 'Lubell, Yoel']",Am J Trop Med Hyg,,,True
60e90014639fac9340b55ac7a08c176393b600bb,PMC,Prevalence of Group A Streptococcus in Primary Care Patients and the Utility of C-Reactive Protein and Clinical Scores for Its Identification in Thailand,http://dx.doi.org/10.4269/ajtmh.19-0502,PMC7008346,31889507,CC BY,"Pharyngitis is usually caused by a viral infection for which antibiotics are often unnecessarily prescribed, adding to the burden of antimicrobial resistance. Identifying who needs antibiotics is challenging; microbiological confirmation and clinical scores are used but have limitations. In a cross-sectional study nested within a randomized controlled trial, we estimated the prevalence and antibiotic susceptibility profiles of group A Streptococcus (GAS) in patients presenting to primary care with a sore throat and fever in northern Thailand. We then evaluated the use of C-reactive protein (CRP) and clinical scores (Centor and FeverPAIN) to identify the presence of GAS. One hundred sixty-nine patients were enrolled, of whom 35 (20.7%) had β-hemolytic Streptococci (BHS) isolated from throat swab culture, and 11 (6.5%) had GAS. All GAS isolates were sensitive to penicillin G. The median CRP of those without BHS isolation was 10 mg/L (interquartile range [IQR] ≤ 8–18), compared with 18 mg/L (IQR 9–71, P = 0.0302) for those with GAS and 14 mg/L (IQR ≤ 8–38, P = 0.0516) for those with any BHS isolated. However, there were no significant relationships between CRP > 8 mg/L (P = 0.112), Centor ≥ 3 (P = 0.212), and FeverPAIN ≥ 4 (P = 1.000), and the diagnosis of GAS compared with no BHS isolation. Identifying who requires antibiotics for pharyngitis remains challenging and necessitates further larger studies. C-reactive protein testing alone, although imperfect, can reduce prescribing compared with routine care. Targeted CRP testing through clinical scoring may be the most cost-effective approach to ruling out GAS infection.",2020 Feb 30,"['Greer, Rachel', 'Althaus, Thomas', 'Ling, Clare', 'Intralawan, Daranee', 'Nedsuwan, Supalert', 'Thaipadungpanit, Janjira', 'Wangrangsimakul, Tri', 'Butler, Christopher', 'Day, Nicolas', 'Lubell, Yoel']",Am J Trop Med Hyg,,,False
1029b20dd40ca982d05b80adad4c125beb10217b,PMC,Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation,http://dx.doi.org/10.1371/journal.pgen.1008537,PMC7010298,31961859,CC BY,"Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin. Regulatory element activity is in turn modulated by genetic variation, resulting in variable transcription rates across individuals. The interplay of these factors, however, is poorly understood. Here we characterize expression and chromatin state dynamics across three tissues—liver, lung, and kidney—in 47 strains of the Collaborative Cross (CC) mouse population, examining the regulation of these dynamics by expression quantitative trait loci (eQTL) and chromatin QTL (cQTL). QTL whose allelic effects were consistent across tissues were detected for 1,101 genes and 133 chromatin regions. Also detected were eQTL and cQTL whose allelic effects differed across tissues, including local-eQTL for Pik3c2g detected in all three tissues but with distinct allelic effects. Leveraging overlapping measurements of gene expression and chromatin accessibility on the same mice from multiple tissues, we used mediation analysis to identify chromatin and gene expression intermediates of eQTL effects. Based on QTL and mediation analyses over multiple tissues, we propose a causal model for the distal genetic regulation of Akr1e1, a gene involved in glycogen metabolism, through the zinc finger transcription factor Zfp985 and chromatin intermediates. This analysis demonstrates the complexity of transcriptional and chromatin dynamics and their regulation over multiple tissues, as well as the value of the CC and related genetic resource populations for identifying specific regulatory mechanisms within cells and tissues.",2020 Jan 21,"['Keele, Gregory R.', 'Quach, Bryan C.', 'Israel, Jennifer W.', 'Chappell, Grace A.', 'Lewis, Lauren', 'Safi, Alexias', 'Simon, Jeremy M.', 'Cotney, Paul', 'Crawford, Gregory E.', 'Valdar, William', 'Rusyn, Ivan', 'Furey, Terrence S.']",PLoS Genet,,,True
f5ed30bc906fca5572d04c5258cfec3d91093058,PMC,Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation,http://dx.doi.org/10.1371/journal.pgen.1008537,PMC7010298,31961859,CC BY,"Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin. Regulatory element activity is in turn modulated by genetic variation, resulting in variable transcription rates across individuals. The interplay of these factors, however, is poorly understood. Here we characterize expression and chromatin state dynamics across three tissues—liver, lung, and kidney—in 47 strains of the Collaborative Cross (CC) mouse population, examining the regulation of these dynamics by expression quantitative trait loci (eQTL) and chromatin QTL (cQTL). QTL whose allelic effects were consistent across tissues were detected for 1,101 genes and 133 chromatin regions. Also detected were eQTL and cQTL whose allelic effects differed across tissues, including local-eQTL for Pik3c2g detected in all three tissues but with distinct allelic effects. Leveraging overlapping measurements of gene expression and chromatin accessibility on the same mice from multiple tissues, we used mediation analysis to identify chromatin and gene expression intermediates of eQTL effects. Based on QTL and mediation analyses over multiple tissues, we propose a causal model for the distal genetic regulation of Akr1e1, a gene involved in glycogen metabolism, through the zinc finger transcription factor Zfp985 and chromatin intermediates. This analysis demonstrates the complexity of transcriptional and chromatin dynamics and their regulation over multiple tissues, as well as the value of the CC and related genetic resource populations for identifying specific regulatory mechanisms within cells and tissues.",2020 Jan 21,"['Keele, Gregory R.', 'Quach, Bryan C.', 'Israel, Jennifer W.', 'Chappell, Grace A.', 'Lewis, Lauren', 'Safi, Alexias', 'Simon, Jeremy M.', 'Cotney, Paul', 'Crawford, Gregory E.', 'Valdar, William', 'Rusyn, Ivan', 'Furey, Terrence S.']",PLoS Genet,,,False
c7d1c17055c7320e8d2a0cca313bddc7dcb3d401,PMC,Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation,http://dx.doi.org/10.1371/journal.pgen.1008537,PMC7010298,31961859,CC BY,"Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin. Regulatory element activity is in turn modulated by genetic variation, resulting in variable transcription rates across individuals. The interplay of these factors, however, is poorly understood. Here we characterize expression and chromatin state dynamics across three tissues—liver, lung, and kidney—in 47 strains of the Collaborative Cross (CC) mouse population, examining the regulation of these dynamics by expression quantitative trait loci (eQTL) and chromatin QTL (cQTL). QTL whose allelic effects were consistent across tissues were detected for 1,101 genes and 133 chromatin regions. Also detected were eQTL and cQTL whose allelic effects differed across tissues, including local-eQTL for Pik3c2g detected in all three tissues but with distinct allelic effects. Leveraging overlapping measurements of gene expression and chromatin accessibility on the same mice from multiple tissues, we used mediation analysis to identify chromatin and gene expression intermediates of eQTL effects. Based on QTL and mediation analyses over multiple tissues, we propose a causal model for the distal genetic regulation of Akr1e1, a gene involved in glycogen metabolism, through the zinc finger transcription factor Zfp985 and chromatin intermediates. This analysis demonstrates the complexity of transcriptional and chromatin dynamics and their regulation over multiple tissues, as well as the value of the CC and related genetic resource populations for identifying specific regulatory mechanisms within cells and tissues.",2020 Jan 21,"['Keele, Gregory R.', 'Quach, Bryan C.', 'Israel, Jennifer W.', 'Chappell, Grace A.', 'Lewis, Lauren', 'Safi, Alexias', 'Simon, Jeremy M.', 'Cotney, Paul', 'Crawford, Gregory E.', 'Valdar, William', 'Rusyn, Ivan', 'Furey, Terrence S.']",PLoS Genet,,,True
ae8b139ede9460926a290fbae525b59fbe0e5c53,PMC,Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation,http://dx.doi.org/10.1371/journal.pgen.1008537,PMC7010298,31961859,CC BY,"Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin. Regulatory element activity is in turn modulated by genetic variation, resulting in variable transcription rates across individuals. The interplay of these factors, however, is poorly understood. Here we characterize expression and chromatin state dynamics across three tissues—liver, lung, and kidney—in 47 strains of the Collaborative Cross (CC) mouse population, examining the regulation of these dynamics by expression quantitative trait loci (eQTL) and chromatin QTL (cQTL). QTL whose allelic effects were consistent across tissues were detected for 1,101 genes and 133 chromatin regions. Also detected were eQTL and cQTL whose allelic effects differed across tissues, including local-eQTL for Pik3c2g detected in all three tissues but with distinct allelic effects. Leveraging overlapping measurements of gene expression and chromatin accessibility on the same mice from multiple tissues, we used mediation analysis to identify chromatin and gene expression intermediates of eQTL effects. Based on QTL and mediation analyses over multiple tissues, we propose a causal model for the distal genetic regulation of Akr1e1, a gene involved in glycogen metabolism, through the zinc finger transcription factor Zfp985 and chromatin intermediates. This analysis demonstrates the complexity of transcriptional and chromatin dynamics and their regulation over multiple tissues, as well as the value of the CC and related genetic resource populations for identifying specific regulatory mechanisms within cells and tissues.",2020 Jan 21,"['Keele, Gregory R.', 'Quach, Bryan C.', 'Israel, Jennifer W.', 'Chappell, Grace A.', 'Lewis, Lauren', 'Safi, Alexias', 'Simon, Jeremy M.', 'Cotney, Paul', 'Crawford, Gregory E.', 'Valdar, William', 'Rusyn, Ivan', 'Furey, Terrence S.']",PLoS Genet,,,True
da2ee9c8dffbd4a2fe553d09e85bc0d99f8a92bf,PMC,Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation,http://dx.doi.org/10.1371/journal.pgen.1008537,PMC7010298,31961859,CC BY,"Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin. Regulatory element activity is in turn modulated by genetic variation, resulting in variable transcription rates across individuals. The interplay of these factors, however, is poorly understood. Here we characterize expression and chromatin state dynamics across three tissues—liver, lung, and kidney—in 47 strains of the Collaborative Cross (CC) mouse population, examining the regulation of these dynamics by expression quantitative trait loci (eQTL) and chromatin QTL (cQTL). QTL whose allelic effects were consistent across tissues were detected for 1,101 genes and 133 chromatin regions. Also detected were eQTL and cQTL whose allelic effects differed across tissues, including local-eQTL for Pik3c2g detected in all three tissues but with distinct allelic effects. Leveraging overlapping measurements of gene expression and chromatin accessibility on the same mice from multiple tissues, we used mediation analysis to identify chromatin and gene expression intermediates of eQTL effects. Based on QTL and mediation analyses over multiple tissues, we propose a causal model for the distal genetic regulation of Akr1e1, a gene involved in glycogen metabolism, through the zinc finger transcription factor Zfp985 and chromatin intermediates. This analysis demonstrates the complexity of transcriptional and chromatin dynamics and their regulation over multiple tissues, as well as the value of the CC and related genetic resource populations for identifying specific regulatory mechanisms within cells and tissues.",2020 Jan 21,"['Keele, Gregory R.', 'Quach, Bryan C.', 'Israel, Jennifer W.', 'Chappell, Grace A.', 'Lewis, Lauren', 'Safi, Alexias', 'Simon, Jeremy M.', 'Cotney, Paul', 'Crawford, Gregory E.', 'Valdar, William', 'Rusyn, Ivan', 'Furey, Terrence S.']",PLoS Genet,,,False
cd57034187ff47256ee511723a6a05b18a923026,PMC,Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation,http://dx.doi.org/10.1371/journal.pgen.1008537,PMC7010298,31961859,CC BY,"Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin. Regulatory element activity is in turn modulated by genetic variation, resulting in variable transcription rates across individuals. The interplay of these factors, however, is poorly understood. Here we characterize expression and chromatin state dynamics across three tissues—liver, lung, and kidney—in 47 strains of the Collaborative Cross (CC) mouse population, examining the regulation of these dynamics by expression quantitative trait loci (eQTL) and chromatin QTL (cQTL). QTL whose allelic effects were consistent across tissues were detected for 1,101 genes and 133 chromatin regions. Also detected were eQTL and cQTL whose allelic effects differed across tissues, including local-eQTL for Pik3c2g detected in all three tissues but with distinct allelic effects. Leveraging overlapping measurements of gene expression and chromatin accessibility on the same mice from multiple tissues, we used mediation analysis to identify chromatin and gene expression intermediates of eQTL effects. Based on QTL and mediation analyses over multiple tissues, we propose a causal model for the distal genetic regulation of Akr1e1, a gene involved in glycogen metabolism, through the zinc finger transcription factor Zfp985 and chromatin intermediates. This analysis demonstrates the complexity of transcriptional and chromatin dynamics and their regulation over multiple tissues, as well as the value of the CC and related genetic resource populations for identifying specific regulatory mechanisms within cells and tissues.",2020 Jan 21,"['Keele, Gregory R.', 'Quach, Bryan C.', 'Israel, Jennifer W.', 'Chappell, Grace A.', 'Lewis, Lauren', 'Safi, Alexias', 'Simon, Jeremy M.', 'Cotney, Paul', 'Crawford, Gregory E.', 'Valdar, William', 'Rusyn, Ivan', 'Furey, Terrence S.']",PLoS Genet,,,False
99ddf002fab47d2cc14cade8dd958079f27de9f1,PMC,Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation,http://dx.doi.org/10.1371/journal.pgen.1008537,PMC7010298,31961859,CC BY,"Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin. Regulatory element activity is in turn modulated by genetic variation, resulting in variable transcription rates across individuals. The interplay of these factors, however, is poorly understood. Here we characterize expression and chromatin state dynamics across three tissues—liver, lung, and kidney—in 47 strains of the Collaborative Cross (CC) mouse population, examining the regulation of these dynamics by expression quantitative trait loci (eQTL) and chromatin QTL (cQTL). QTL whose allelic effects were consistent across tissues were detected for 1,101 genes and 133 chromatin regions. Also detected were eQTL and cQTL whose allelic effects differed across tissues, including local-eQTL for Pik3c2g detected in all three tissues but with distinct allelic effects. Leveraging overlapping measurements of gene expression and chromatin accessibility on the same mice from multiple tissues, we used mediation analysis to identify chromatin and gene expression intermediates of eQTL effects. Based on QTL and mediation analyses over multiple tissues, we propose a causal model for the distal genetic regulation of Akr1e1, a gene involved in glycogen metabolism, through the zinc finger transcription factor Zfp985 and chromatin intermediates. This analysis demonstrates the complexity of transcriptional and chromatin dynamics and their regulation over multiple tissues, as well as the value of the CC and related genetic resource populations for identifying specific regulatory mechanisms within cells and tissues.",2020 Jan 21,"['Keele, Gregory R.', 'Quach, Bryan C.', 'Israel, Jennifer W.', 'Chappell, Grace A.', 'Lewis, Lauren', 'Safi, Alexias', 'Simon, Jeremy M.', 'Cotney, Paul', 'Crawford, Gregory E.', 'Valdar, William', 'Rusyn, Ivan', 'Furey, Terrence S.']",PLoS Genet,,,False
dc6a965892f97d3eab6d2b9e52e36bd3754844c3,PMC,Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation,http://dx.doi.org/10.1371/journal.pgen.1008537,PMC7010298,31961859,CC BY,"Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin. Regulatory element activity is in turn modulated by genetic variation, resulting in variable transcription rates across individuals. The interplay of these factors, however, is poorly understood. Here we characterize expression and chromatin state dynamics across three tissues—liver, lung, and kidney—in 47 strains of the Collaborative Cross (CC) mouse population, examining the regulation of these dynamics by expression quantitative trait loci (eQTL) and chromatin QTL (cQTL). QTL whose allelic effects were consistent across tissues were detected for 1,101 genes and 133 chromatin regions. Also detected were eQTL and cQTL whose allelic effects differed across tissues, including local-eQTL for Pik3c2g detected in all three tissues but with distinct allelic effects. Leveraging overlapping measurements of gene expression and chromatin accessibility on the same mice from multiple tissues, we used mediation analysis to identify chromatin and gene expression intermediates of eQTL effects. Based on QTL and mediation analyses over multiple tissues, we propose a causal model for the distal genetic regulation of Akr1e1, a gene involved in glycogen metabolism, through the zinc finger transcription factor Zfp985 and chromatin intermediates. This analysis demonstrates the complexity of transcriptional and chromatin dynamics and their regulation over multiple tissues, as well as the value of the CC and related genetic resource populations for identifying specific regulatory mechanisms within cells and tissues.",2020 Jan 21,"['Keele, Gregory R.', 'Quach, Bryan C.', 'Israel, Jennifer W.', 'Chappell, Grace A.', 'Lewis, Lauren', 'Safi, Alexias', 'Simon, Jeremy M.', 'Cotney, Paul', 'Crawford, Gregory E.', 'Valdar, William', 'Rusyn, Ivan', 'Furey, Terrence S.']",PLoS Genet,,,False
1688f949c06ead7b1c557f4dea2b71cfa4e6aff8,PMC,Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation,http://dx.doi.org/10.1371/journal.pgen.1008537,PMC7010298,31961859,CC BY,"Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin. Regulatory element activity is in turn modulated by genetic variation, resulting in variable transcription rates across individuals. The interplay of these factors, however, is poorly understood. Here we characterize expression and chromatin state dynamics across three tissues—liver, lung, and kidney—in 47 strains of the Collaborative Cross (CC) mouse population, examining the regulation of these dynamics by expression quantitative trait loci (eQTL) and chromatin QTL (cQTL). QTL whose allelic effects were consistent across tissues were detected for 1,101 genes and 133 chromatin regions. Also detected were eQTL and cQTL whose allelic effects differed across tissues, including local-eQTL for Pik3c2g detected in all three tissues but with distinct allelic effects. Leveraging overlapping measurements of gene expression and chromatin accessibility on the same mice from multiple tissues, we used mediation analysis to identify chromatin and gene expression intermediates of eQTL effects. Based on QTL and mediation analyses over multiple tissues, we propose a causal model for the distal genetic regulation of Akr1e1, a gene involved in glycogen metabolism, through the zinc finger transcription factor Zfp985 and chromatin intermediates. This analysis demonstrates the complexity of transcriptional and chromatin dynamics and their regulation over multiple tissues, as well as the value of the CC and related genetic resource populations for identifying specific regulatory mechanisms within cells and tissues.",2020 Jan 21,"['Keele, Gregory R.', 'Quach, Bryan C.', 'Israel, Jennifer W.', 'Chappell, Grace A.', 'Lewis, Lauren', 'Safi, Alexias', 'Simon, Jeremy M.', 'Cotney, Paul', 'Crawford, Gregory E.', 'Valdar, William', 'Rusyn, Ivan', 'Furey, Terrence S.']",PLoS Genet,,,False
03eb7f4f076037e60c155e827678b17caa56eddb,PMC,Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation,http://dx.doi.org/10.1371/journal.pgen.1008537,PMC7010298,31961859,CC BY,"Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin. Regulatory element activity is in turn modulated by genetic variation, resulting in variable transcription rates across individuals. The interplay of these factors, however, is poorly understood. Here we characterize expression and chromatin state dynamics across three tissues—liver, lung, and kidney—in 47 strains of the Collaborative Cross (CC) mouse population, examining the regulation of these dynamics by expression quantitative trait loci (eQTL) and chromatin QTL (cQTL). QTL whose allelic effects were consistent across tissues were detected for 1,101 genes and 133 chromatin regions. Also detected were eQTL and cQTL whose allelic effects differed across tissues, including local-eQTL for Pik3c2g detected in all three tissues but with distinct allelic effects. Leveraging overlapping measurements of gene expression and chromatin accessibility on the same mice from multiple tissues, we used mediation analysis to identify chromatin and gene expression intermediates of eQTL effects. Based on QTL and mediation analyses over multiple tissues, we propose a causal model for the distal genetic regulation of Akr1e1, a gene involved in glycogen metabolism, through the zinc finger transcription factor Zfp985 and chromatin intermediates. This analysis demonstrates the complexity of transcriptional and chromatin dynamics and their regulation over multiple tissues, as well as the value of the CC and related genetic resource populations for identifying specific regulatory mechanisms within cells and tissues.",2020 Jan 21,"['Keele, Gregory R.', 'Quach, Bryan C.', 'Israel, Jennifer W.', 'Chappell, Grace A.', 'Lewis, Lauren', 'Safi, Alexias', 'Simon, Jeremy M.', 'Cotney, Paul', 'Crawford, Gregory E.', 'Valdar, William', 'Rusyn, Ivan', 'Furey, Terrence S.']",PLoS Genet,,,False
66b3f855c0f3f5005b0f3c1d75571aed8ca64b43,PMC,Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation,http://dx.doi.org/10.1371/journal.pgen.1008537,PMC7010298,31961859,CC BY,"Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin. Regulatory element activity is in turn modulated by genetic variation, resulting in variable transcription rates across individuals. The interplay of these factors, however, is poorly understood. Here we characterize expression and chromatin state dynamics across three tissues—liver, lung, and kidney—in 47 strains of the Collaborative Cross (CC) mouse population, examining the regulation of these dynamics by expression quantitative trait loci (eQTL) and chromatin QTL (cQTL). QTL whose allelic effects were consistent across tissues were detected for 1,101 genes and 133 chromatin regions. Also detected were eQTL and cQTL whose allelic effects differed across tissues, including local-eQTL for Pik3c2g detected in all three tissues but with distinct allelic effects. Leveraging overlapping measurements of gene expression and chromatin accessibility on the same mice from multiple tissues, we used mediation analysis to identify chromatin and gene expression intermediates of eQTL effects. Based on QTL and mediation analyses over multiple tissues, we propose a causal model for the distal genetic regulation of Akr1e1, a gene involved in glycogen metabolism, through the zinc finger transcription factor Zfp985 and chromatin intermediates. This analysis demonstrates the complexity of transcriptional and chromatin dynamics and their regulation over multiple tissues, as well as the value of the CC and related genetic resource populations for identifying specific regulatory mechanisms within cells and tissues.",2020 Jan 21,"['Keele, Gregory R.', 'Quach, Bryan C.', 'Israel, Jennifer W.', 'Chappell, Grace A.', 'Lewis, Lauren', 'Safi, Alexias', 'Simon, Jeremy M.', 'Cotney, Paul', 'Crawford, Gregory E.', 'Valdar, William', 'Rusyn, Ivan', 'Furey, Terrence S.']",PLoS Genet,,,False
b287ba995f0d86627890bf70c5d6aad88deff2c4,PMC,Specific Integration of Temperate Phage Decreases the Pathogenicity of Host Bacteria,http://dx.doi.org/10.3389/fcimb.2020.00014,PMC7010805,32117795,CC BY,"Temperate phages are considered as natural vectors for gene transmission among bacteria due to the ability to integrate their genomes into a host chromosome, therefore, affect the fitness and phenotype of host bacteria. Many virulence genes of pathogenic bacteria were identified in temperate phage genomes, supporting the concept that temperate phages play important roles in increasing the bacterial pathogenicity through delivery of the virulence genes. However, little is known about the roles of temperate phages in attenuation of bacterial virulence. Here, we report a novel Bordetella bronchiseptica temperate phage, vB_BbrS_PHB09 (PHB09), which has a 42,129-bp dsDNA genome with a G+C content of 62.8%. Phylogenetic analysis based on large terminase subunit indicated that phage PHB09 represented a new member of the family Siphoviridae. The genome of PHB09 contains genes encoding lysogen-associated proteins, including integrase and cI protein. The integration site of PHB09 is specifically located within a pilin gene of B. bronchiseptica. Importantly, we found that the integration of phage PHB09 significantly decreased the virulence of parental strain B. bronchiseptica Bb01 in mice, most likely through disruption the expression of pilin gene. Moreover, a single shot of the prophage bearing B. bronchiseptica strain completely protected mice against lethal challenge with wild-type virulent B. bronchiseptica, indicating the vaccine potential of lysogenized strain. Our findings not only indicate the complicated roles of temperate phages in bacterial virulence other than simple delivery of virulent genes but also provide a potential strategy for developing bacterial vaccines.",2020 Feb 4,"['Chen, Yibao', 'Yang, Lan', 'Yang, Dan', 'Song, Jiaoyang', 'Wang, Can', 'Sun, Erchao', 'Gu, Changqin', 'Chen, Huanchun', 'Tong, Yigang', 'Tao, Pan', 'Wu, Bin']",Front Cell Infect Microbiol,,,True
46c464442591d7777212f7ee389bcbfa362ddc8e,PMC,A case for a negative-strand coding sequence in a group of positive-sense RNA viruses,http://dx.doi.org/10.1093/ve/veaa007,PMC7010960,32064120,CC BY,"Positive-sense single-stranded RNA viruses form the largest and most diverse group of eukaryote-infecting viruses. Their genomes comprise one or more segments of coding-sense RNA that function directly as messenger RNAs upon release into the cytoplasm of infected cells. Positive-sense RNA viruses are generally accepted to encode proteins solely on the positive strand. However, we previously identified a surprisingly long (∼1,000-codon) open reading frame (ORF) on the negative strand of some members of the family Narnaviridae which, together with RNA bacteriophages of the family Leviviridae, form a sister group to all other positive-sense RNA viruses. Here, we completed the genomes of three mosquito-associated narnaviruses, all of which have the long reverse-frame ORF. We systematically identified narnaviral sequences in public data sets from a wide range of sources, including arthropod, fungal, and plant transcriptomic data sets. Long reverse-frame ORFs are widespread in one clade of narnaviruses, where they frequently occupy >95 per cent of the genome. The reverse-frame ORFs correspond to a specific avoidance of CUA, UUA, and UCA codons (i.e. stop codon reverse complements) in the forward-frame RNA-dependent RNA polymerase ORF. However, absence of these codons cannot be explained by other factors such as inability to decode these codons or GC3 bias. Together with other analyses, we provide the strongest evidence yet of coding capacity on the negative strand of a positive-sense RNA virus. As these ORFs comprise some of the longest known overlapping genes, their study may be of broad relevance to understanding overlapping gene evolution and de novo origin of genes.",2020 Feb 10,"['Dinan, Adam M', 'Lukhovitskaya, Nina I', 'Olendraite, Ingrida', 'Firth, Andrew E']",Virus Evol,,,True
13af5f3171885fd9385c4320e14ce219aa345022,PMC,An interim review of the epidemiological characteristics of 2019 novel coronavirus,http://dx.doi.org/10.4178/epih.e2020006,PMC7011107,32023775,CC BY,"OBJECTIVES: The 2019 novel coronavirus (2019-nCoV) from Wuhan, China is currently recognized as a public health emergency of global concern. METHODS: We reviewed the currently available literature to provide up-to-date guidance on control measures to be implemented by public health authorities. RESULTS: Some of the epidemiological characteristics of 2019-nCoV have been identified. However, there remain considerable uncertainties, which should be considered when providing guidance to public health authorities on control measures. CONCLUSIONS: Additional studies incorporating more detailed information from confirmed cases would be valuable.",2020 Feb 6,"['Ryu, Sukhyun', 'Chun, Byung Chul', None]",Epidemiol Health,,,True
256425602cf068d42a6473d317890d0c0ac6a464,PMC,Emojis in public health and how they might be used for hand hygiene and infection prevention and control,http://dx.doi.org/10.1186/s13756-020-0692-2,PMC7011445,32041666,CC BY,"Emojis are frequently used picture characters known as possible surrogates for non-verbal aspects of behavior. Considering the ability of emojis to enhance and facilitate communication, there has been a growing interest in studying their effects in scientific and health-related topics over the past few years. Infection prevention and control (IPC) is a field of medicine that is directly associated with specific behaviors. These include hand hygiene, which is the cornerstone of the prevention of healthcare-associated infections, and essential in stemming the spread of antimicrobial resistance. This paper aims to provide an overview of how emojis have been used in the medical and public health literature and proposes their possible use in IPC and hand hygiene to put forth a vision for the future research.",2020 Feb 10,"['Lotfinejad, Nasim', 'Assadi, Reza', 'Aelami, Mohammad Hassan', 'Pittet, Didier']",Antimicrob Resist Infect Control,,,True
35346aa2228281a39b64a6185827e497e57296a3,PMC,"PEDV enters cells through clathrin-, caveolae-, and lipid raft-mediated endocytosis and traffics via the endo-/lysosome pathway",http://dx.doi.org/10.1186/s13567-020-0739-7,PMC7011528,32041637,CC BY,"With the emergence of highly pathogenic variant strains, porcine epidemic diarrhea virus (PEDV) has led to significant economic loss in the global swine industry. Many studies have described how coronaviruses enter cells, but information on PEDV invasion strategies remains insufficient. Given that the differences in gene sequences and pathogenicity between classical and mutant strains of PEDV may lead to diverse invasion mechanisms, this study focused on the cellular entry pathways and cellular transport of the PEDV GI and GII subtype strains in Vero cells and IPEC-J2 cells. We first characterized the kinetics of PEDV entry into cells and found that the highest invasion rate of PEDV was approximately 33% in the IPEC-J2 cells and approximately 100% in the Vero cells. To clarify the specific endocytic pathways, systematic research methods were used and showed that PEDV enters cells via the clathrin- and caveolae-mediated endocytosis pathways, in which dynamin II, clathrin heavy chain, Eps15, cholesterol, and caveolin-1 were indispensably involved. In addition, lipid raft extraction assay showed that PEDV can also enter cells through lipid raft-mediated endocytosis. To investigate the trafficking of internalized PEDV, we found that PEDV entry into cells relied on low pH and internalized virions reached lysosomes through the early endosome–late endosome–lysosome pathway. The results concretely revealed the entry mechanisms of PEDV and provided an insightful theoretical basis for the further understanding of PEDV pathogenesis and guidance for new targets of antiviral drugs.",2020 Feb 10,"['Wei, Xiaona', 'She, Gaoli', 'Wu, Tingting', 'Xue, Chunyi', 'Cao, Yongchang']",Vet Res,,,True
f481624491ae43193cf1229d54d99e8ddcef9479,PMC,Respiratory Barrier as a Safeguard and Regulator of Defense Against Influenza A Virus and Streptococcus pneumoniae,http://dx.doi.org/10.3389/fimmu.2020.00003,PMC7011736,32117216,CC BY,"The primary function of the respiratory system of gas exchange renders it vulnerable to environmental pathogens that circulate in the air. Physical and cellular barriers of the respiratory tract mucosal surface utilize a variety of strategies to obstruct microbe entry. Physical barrier defenses including the surface fluid replete with antimicrobials, neutralizing immunoglobulins, mucus, and the epithelial cell layer with rapidly beating cilia form a near impenetrable wall that separates the external environment from the internal soft tissue of the host. Resident leukocytes, primarily of the innate immune branch, also maintain airway integrity by constant surveillance and the maintenance of homeostasis through the release of cytokines and growth factors. Unfortunately, pathogens such as influenza virus and Streptococcus pneumoniae require hosts for their replication and dissemination, and prey on the respiratory tract as an ideal environment causing severe damage to the host during their invasion. In this review, we outline the host-pathogen interactions during influenza and post-influenza bacterial pneumonia with a focus on inter- and intra-cellular crosstalk important in pulmonary immune responses.",2020 Feb 4,"['LeMessurier, Kim S.', 'Tiwary, Meenakshi', 'Morin, Nicholas P.', 'Samarasinghe, Amali E.']",Front Immunol,,,True
f6fad98294179598664366ea99a8caa991b74340,PMC,Virus interactions with bacteria: Partners in the infectious dance,http://dx.doi.org/10.1371/journal.ppat.1008234,PMC7012391,32045465,CC BY,,2020 Feb 11,"['Neu, Ursula', 'Mainou, Bernardo A.']",PLoS Pathog,,,True
069bf4da8f0f4f540b9f6a16021e007442e7e027,PMC,"MyD88-dependent influx of monocytes and neutrophils impairs lymph node B cell responses to chikungunya virus infection via Irf5, Nos2 and Nox2",http://dx.doi.org/10.1371/journal.ppat.1008292,PMC7012455,31999809,CC0,"Humoral immune responses initiate in the lymph node draining the site of viral infection (dLN). Some viruses subvert LN B cell activation; however, our knowledge of viral hindrance of B cell responses of important human pathogens is lacking. Here, we define mechanisms whereby chikungunya virus (CHIKV), a mosquito-transmitted RNA virus that causes outbreaks of acute and chronic arthritis in humans, hinders dLN antiviral B cell responses. Infection of WT mice with pathogenic, but not acutely cleared CHIKV, induced MyD88-dependent recruitment of monocytes and neutrophils to the dLN. Blocking this influx improved lymphocyte accumulation, dLN organization, and CHIKV-specific B cell responses. Both inducible nitric oxide synthase (iNOS) and the phagocyte NADPH oxidase (Nox2) contributed to impaired dLN organization and function. Infiltrating monocytes expressed iNOS through a local IRF5- and IFNAR1-dependent pathway that was partially TLR7-dependent. Together, our data suggest that pathogenic CHIKV triggers the influx and activation of monocytes and neutrophils in the dLN that impairs virus-specific B cell responses.",2020 Jan 30,"['McCarthy, Mary K.', 'Reynoso, Glennys V.', 'Winkler, Emma S.', 'Mack, Matthias', 'Diamond, Michael S.', 'Hickman, Heather D.', 'Morrison, Thomas E.']",PLoS Pathog,,,True
53da3d32d1193129d3366af8aee4bc9a4224aa46,PMC,"MyD88-dependent influx of monocytes and neutrophils impairs lymph node B cell responses to chikungunya virus infection via Irf5, Nos2 and Nox2",http://dx.doi.org/10.1371/journal.ppat.1008292,PMC7012455,31999809,CC0,"Humoral immune responses initiate in the lymph node draining the site of viral infection (dLN). Some viruses subvert LN B cell activation; however, our knowledge of viral hindrance of B cell responses of important human pathogens is lacking. Here, we define mechanisms whereby chikungunya virus (CHIKV), a mosquito-transmitted RNA virus that causes outbreaks of acute and chronic arthritis in humans, hinders dLN antiviral B cell responses. Infection of WT mice with pathogenic, but not acutely cleared CHIKV, induced MyD88-dependent recruitment of monocytes and neutrophils to the dLN. Blocking this influx improved lymphocyte accumulation, dLN organization, and CHIKV-specific B cell responses. Both inducible nitric oxide synthase (iNOS) and the phagocyte NADPH oxidase (Nox2) contributed to impaired dLN organization and function. Infiltrating monocytes expressed iNOS through a local IRF5- and IFNAR1-dependent pathway that was partially TLR7-dependent. Together, our data suggest that pathogenic CHIKV triggers the influx and activation of monocytes and neutrophils in the dLN that impairs virus-specific B cell responses.",2020 Jan 30,"['McCarthy, Mary K.', 'Reynoso, Glennys V.', 'Winkler, Emma S.', 'Mack, Matthias', 'Diamond, Michael S.', 'Hickman, Heather D.', 'Morrison, Thomas E.']",PLoS Pathog,,,True
9002b1efb25414c9e3ea87ad89e6c9be39fdff24,PMC,Travel-Related Typhoid Fever: Narrative Review of the Scientific Literature,http://dx.doi.org/10.3390/ijerph17020615,PMC7013505,31963643,CC BY,"Enteric fever is a foodborne infectious disease caused by Salmonella enterica serotypes Typhi and Paratyphi A, B and C. The high incidence in low income countries can increase the risk of disease in travelers coming from high income countries. Pre-travel health advice on hygiene and sanitation practices and vaccines can significantly reduce the risk of acquiring infections. Although the majority of the cases are self-limiting, life-threatening complications can occur. Delayed diagnosis and cases of infections caused by multi-drug resistant strains can complicate the clinical management and affect the prognosis. More international efforts are needed to reduce the burden of disease in low income countries, indirectly reducing the risk of travelers in endemic settings. Surveillance activities can help monitor the epidemiology of cases caused by drug-susceptible and resistant strains.",2020 Jan 18,"['Muresu, Narcisa', 'Sotgiu, Giovanni', 'Are, Bianca Maria', 'Cossu, Andrea', 'Cocuzza, Clementina', 'Martinelli, Marianna', 'Babudieri, Sergio', 'Are, Riccardo', 'Dettori, Marco', 'Azara, Antonio', 'Saderi, Laura', 'Piana, Andrea']",Int J Environ Res Public Health,,,True
fd4ab143e7dd8db7255b11177505986e87b50943,PMC,Increased Detection of Viruses in Children with Respiratory Tract Infection Using PCR,http://dx.doi.org/10.3390/ijerph17020564,PMC7013517,31952364,CC BY,"Respiratory viruses are a common cause of respiratory tract infection (RTI), particularly in neonates and children. Rapid and accurate diagnosis of viral infections could improve clinical outcomes and reduce the use of antibiotics and treatment sessions. Advances in diagnostic technology contribute to the accurate detection of viruses. We performed a multiplex real-time polymerase chain reaction (PCR) to investigate the viral etiology in pediatric patients and compared the detection rates with those determined using traditional antigen tests and virus cultures. Fifteen respiratory viruses were included in our investigation: respiratory syncytial virus A/B (RSV), influenza virus A (FluA) and influenza virus B (FluB), human metapneumovirus (MPV), enterovirus (EV), human parainfluenza virus (PIV) types 1–4, human rhinovirus (RV), human coronavirus OC43, NL63, and 229E, human adenovirus (ADV), and human bocavirus (Boca). In total, 474 specimens were collected and tested. Respiratory viruses were detected more frequently by PCR (357, 75.3%) than they were by traditional tests (229, 49.3%). The leading pathogens were RSV (113, 23.8%), RV (72, 15.2%), PIV3 (53, 11.2%), FluA (51, 10.8%), and ADV (48, 10.1%). For children younger than 5 years, RSV and RV were most prevalent; for children older than 5 years, FluA and ADV were the most frequently detected. Of the specimens, 25.8% (92/357) were coinfected with two or more viruses. RV, Boca, PIV2, FluB, and PIV4 had higher rates of coinfection; MPV and PIV1 had the lowest rates of coinfection (9.1% and 5.3%). To conclude, the detection power of PCR was better than that of traditional antigen tests and virus cultures when considering the detection of respiratory viruses. RSV and RV were the leading viral pathogens identified in the respiratory specimens. One-quarter of the positive specimens were coinfected with two or more viruses. In the future, further application of PCR may contribute to the rapid and accurate diagnosis of respiratory viruses and could improve patient outcomes.",2020 Jan 15,"['Lin, Chien-Yu', 'Hwang, David', 'Chiu, Nan-Chang', 'Weng, Li-Chuan', 'Liu, Hsin-Fu', 'Mu, Jung-Jung', 'Liu, Chang-Pan', 'Chi, Hsin']",Int J Environ Res Public Health,,,True
b6b03937c9659ee0caa234835878ed183cf695a1,PMC,Increased Detection of Viruses in Children with Respiratory Tract Infection Using PCR,http://dx.doi.org/10.3390/ijerph17020564,PMC7013517,31952364,CC BY,"Respiratory viruses are a common cause of respiratory tract infection (RTI), particularly in neonates and children. Rapid and accurate diagnosis of viral infections could improve clinical outcomes and reduce the use of antibiotics and treatment sessions. Advances in diagnostic technology contribute to the accurate detection of viruses. We performed a multiplex real-time polymerase chain reaction (PCR) to investigate the viral etiology in pediatric patients and compared the detection rates with those determined using traditional antigen tests and virus cultures. Fifteen respiratory viruses were included in our investigation: respiratory syncytial virus A/B (RSV), influenza virus A (FluA) and influenza virus B (FluB), human metapneumovirus (MPV), enterovirus (EV), human parainfluenza virus (PIV) types 1–4, human rhinovirus (RV), human coronavirus OC43, NL63, and 229E, human adenovirus (ADV), and human bocavirus (Boca). In total, 474 specimens were collected and tested. Respiratory viruses were detected more frequently by PCR (357, 75.3%) than they were by traditional tests (229, 49.3%). The leading pathogens were RSV (113, 23.8%), RV (72, 15.2%), PIV3 (53, 11.2%), FluA (51, 10.8%), and ADV (48, 10.1%). For children younger than 5 years, RSV and RV were most prevalent; for children older than 5 years, FluA and ADV were the most frequently detected. Of the specimens, 25.8% (92/357) were coinfected with two or more viruses. RV, Boca, PIV2, FluB, and PIV4 had higher rates of coinfection; MPV and PIV1 had the lowest rates of coinfection (9.1% and 5.3%). To conclude, the detection power of PCR was better than that of traditional antigen tests and virus cultures when considering the detection of respiratory viruses. RSV and RV were the leading viral pathogens identified in the respiratory specimens. One-quarter of the positive specimens were coinfected with two or more viruses. In the future, further application of PCR may contribute to the rapid and accurate diagnosis of respiratory viruses and could improve patient outcomes.",2020 Jan 15,"['Lin, Chien-Yu', 'Hwang, David', 'Chiu, Nan-Chang', 'Weng, Li-Chuan', 'Liu, Hsin-Fu', 'Mu, Jung-Jung', 'Liu, Chang-Pan', 'Chi, Hsin']",Int J Environ Res Public Health,,,False
67f9fc7574738473d4155929c1637f1e7c36afb2,PMC,Identification of a Novel Linear B-Cell Epitope on the Nucleocapsid Protein of Porcine Deltacoronavirus,http://dx.doi.org/10.3390/ijms21020648,PMC7013544,31963776,CC BY,"Porcine deltacoronavirus (PDCoV), first identified in 2012, is a swine enteropathogen now found in many countries. The nucleocapsid (N) protein, a core component of PDCoV, is essential for virus replication and is a significant candidate in the development of diagnostics for PDCoV. In this study, monoclonal antibodies (mAbs) were generated and tested for reactivity with three truncations of the full protein (N1, N2, N3) that contained partial overlaps; of the five monoclonals chosen tested, each reacted with only the N3 truncation. The antibody designated 4E88 had highest binding affinity with the N protein and was chosen for in-depth examination. The 4E88 epitope was located to amino acids 308-AKPKQQKKPKK-318 by testing the 4E88 monoclonal for reactivity with a series of N3 truncations, then the minimal epitope, 309-KPKQQKKPK-317 (designated EP-4E88), was pinpointed by testing the 4E88 monoclonal for reactivity with a series of synthetic peptides of this region. Homology analysis showed that the EP-4E88 sequence is highly conserved among PDCoV strains, and also shares high similarity with sparrow coronavirus (HKU17), Asian leopard cat coronavirus (ALCCoV), quail coronavirus (UAE-HKU30), and sparrow deltacoronavirus (SpDCoV). Of note, the PDCoV EP-4E88 sequence shared very low similarity (<22.2%) with other porcine coronaviruses (PEDV, TGEV, PRCV, SADS-CoV, PHEV), demonstrating that it is an epitope that can be used for distinguishing PDCoV and other porcine coronavirus. 3D structural analysis revealed that amino acids of EP-4E88 were in close proximity and may be exposed on the surface of the N protein.",2020 Jan 19,"['Fu, Jiayu', 'Chen, Rui', 'Hu, Jingfei', 'Qu, Huan', 'Zhao, Yujia', 'Cao, Sanjie', 'Wen, Xintian', 'Wen, Yiping', 'Wu, Rui', 'Zhao, Qin', 'Ma, Xiaoping', 'Huang, Xiaobo']",Int J Mol Sci,,,True
09e25e413faba97b87efc701d1ab8d2a18386efb,PMC,Effectiveness of airport screening at detecting travellers infected with novel coronavirus (2019-nCoV),http://dx.doi.org/10.2807/1560-7917.ES.2020.25.5.2000080,PMC7014668,32046816,CC BY,"We evaluated effectiveness of thermal passenger screening for 2019-nCoV infection at airport exit and entry to inform public health decision-making. In our baseline scenario, we estimated that 46% (95% confidence interval: 36 to 58) of infected travellers would not be detected, depending on incubation period, sensitivity of exit and entry screening, and proportion of asymptomatic cases. Airport screening is unlikely to detect a sufficient proportion of 2019-nCoV infected travellers to avoid entry of infected travellers.",2020 Feb 6,"['Quilty, Billy J', 'Clifford, Sam', None, 'Flasche, Stefan', 'Eggo, Rosalind M']",Euro Surveill,,,True
975efc500cbcf3160d764fd3808b232bfb9c8673,PMC,Note from the editors: World Health Organization declares novel coronavirus (2019-nCoV) sixth public health emergency of international concern,http://dx.doi.org/10.2807/1560-7917.ES.2020.25.5.200131e,PMC7014669,32019636,CC BY,,2020 Feb 6,,Euro Surveill,,,False
4169c478d00d20c1d3a2a3b5c1684ef749e32041,PMC,"Validation of an Aptima-format Finnish new variant of Chlamydia trachomatis (FI-nvCT) surveillance assay, 2019",http://dx.doi.org/10.2807/1560-7917.ES.2020.25.5.2000038,PMC7014671,32046818,CC BY,"The Finnish new variant of Chlamydia trachomatis (FI-nvCT) is escaping diagnostics in Finland, Norway and Sweden. We have developed and validated an Aptima-format nucleic acid amplification test (NAAT) designed specifically to detect the FI-nvCT. This NAAT has high sensitivity (100%) and specificity (100%) for the FI-nvCT strain, enabling further investigation of the geographic distribution, prevalence and transmission of this diagnostic-escape mutant in screening populations in Europe.",2020 Feb 6,"['Weinbaum, Barbara', 'Williams, Analee', 'Hadad, Ronza', 'Vinluan, Bryan', 'Puolakkainen, Mirja', 'Unemo, Magnus', 'Getman, Damon']",Euro Surveill,,,True
dd41a45ccd8c4801ed131a349aa0ec0bc8f3895c,PMC,"Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020",http://dx.doi.org/10.2807/1560-7917.ES.2020.25.5.2000062,PMC7014672,32046819,CC BY,"A novel coronavirus (2019-nCoV) is causing an outbreak of viral pneumonia that started in Wuhan, China. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan in the early outbreak phase, we estimate the mean incubation period to be 6.4 days (95% credible interval: 5.6–7.7), ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values should help inform 2019-nCoV case definitions and appropriate quarantine durations.",2020 Feb 6,"['Backer, Jantien A', 'Klinkenberg, Don', 'Wallinga, Jacco']",Euro Surveill,,,True
6180801d741a7b821bf100e3040773f298ba4deb,PMC,Unraveling virus relationships by structure-based phylogenetic classification,http://dx.doi.org/10.1093/ve/veaa003,PMC7015158,32064119,CC BY,"Delineation of the intricacies of protein function from macromolecular structure constitutes a continual obstacle in the study of cell and pathogen biology. Structure-based phylogenetic analysis has emerged as a powerful tool for addressing this challenge, allowing the detection and quantification of conserved architectural properties between proteins, including those with low or no detectable sequence homology. With a focus on viral protein structure, we highlight how a number of investigations have utilized this powerful method to infer common functionality and ancestry.",2020 Feb 12,"['Ng, Weng M', 'Stelfox, Alice J', 'Bowden, Thomas A']",Virus Evol,,,True
851a02ef7408469b2f8f97736a4515044daf805c,PMC,Porcine Epidemic Diarrhea Altered Colonic Microbiota Communities in Suckling Piglets,http://dx.doi.org/10.3390/genes11010044,PMC7016528,31905830,CC BY,"Porcine epidemic diarrhea (PED) is a major gastrointestinal disease afflicting suckling pigs that causes huge industrial economic losses. In this study, we investigated microbiota from the colonic mucosa and content in healthy and PED piglets. High-throughput 16S rRNA gene sequencing was performed to identify inter-group differences. Firmicutes, Fusobacteria, Proteobacteria, and Bacteroidetes were the top four affected phyla. The proportion of Proteobacteria was higher in infected than in healthy piglets, and the opposite was observed for Bacteroidetes (more than four-fold higher in the healthy group). In the infected group, Fusobacterium accounted for 36.56% and 21.61% in the colonic mucosa and contents, respectively, while in the healthy group, they comprised 22.53% and 12.67%, respectively. The percentage of Lactobacillus in healthy colons (15.63%) was considerably higher than that in the disease group (<10%). In both the colonic mucosa and contents, functional enrichment differed significantly between healthy and diseased groups. Overall, infection with the PED virus increased the proportion of harmful bacteria and decreased the proportion of beneficial bacteria in the colons of piglets. Targeting intestinal microbiota could be a promising method for PED prevention, thus opening new avenues for future research.",2019 Dec 30,"['Tan, Zhen', 'Dong, Wanting', 'Ding, Yaqun', 'Ding, Xiangdong', 'Zhang, Qin', 'Jiang, Li']",Genes (Basel),,,True
a068f1ec98befb3d767ba602df5f314604f0aee8,PMC,The Ebola Virus Nucleoprotein Recruits the Nuclear RNA Export Factor NXF1 into Inclusion Bodies to Facilitate Viral Protein Expression,http://dx.doi.org/10.3390/cells9010187,PMC7017048,31940815,CC BY,"Ebola virus (EBOV) causes severe outbreaks of viral hemorrhagic fever in humans. While virus-host interactions are promising targets for antivirals, there is only limited knowledge regarding the interactions of EBOV with cellular host factors. Recently, we performed a genome-wide siRNA screen that identified the nuclear RNA export factor 1 (NXF1) as an important host factor for the EBOV life cycle. NXF1 is a major component of the nuclear mRNA export pathway that is usurped by many viruses whose life cycles include nuclear stages. However, the role of NXF1 in the life cycle of EBOV, a virus replicating in cytoplasmic inclusion bodies, remains unknown. In order to better understand the role of NXF1 in the EBOV life cycle, we performed a combination of co-immunoprecipitation and double immunofluorescence assays to characterize the interactions of NXF1 with viral proteins and RNAs. Additionally, using siRNA-mediated knockdown of NXF1 together with functional assays, we analyzed the role of NXF1 in individual aspects of the virus life cycle. With this approach we identified the EBOV nucleoprotein (NP) as a viral interaction partner of NXF1. Further studies revealed that NP interacts with the RNA-binding domain of NXF1 and competes with RNA for this interaction. Co-localization studies showed that RNA binding-deficient, but not wildtype NXF1, accumulates in NP-derived inclusion bodies, and knockdown experiments demonstrated that NXF1 is necessary for viral protein expression, but not for viral RNA synthesis. Finally, our results showed that NXF1 interacts with viral mRNAs, but not with viral genomic RNAs. Based on these results we suggest a model whereby NXF1 is recruited into inclusion bodies to promote the export of viral mRNA:NXF1 complexes from these sites. This would represent a novel function for NXF1 in the life cycle of cytoplasmically replicating viruses, and may provide a basis for new therapeutic approaches against EBOV, and possibly other emerging viruses.",2020 Jan 11,"['Wendt, Lisa', 'Brandt, Janine', 'Bodmer, Bianca S.', 'Reiche, Sven', 'Schmidt, Marie Luisa', 'Traeger, Shelby', 'Hoenen, Thomas']",Cells,,,True
3713ffd44093f5ada28b259799f5202894db25d6,PMC,The Ebola Virus Nucleoprotein Recruits the Nuclear RNA Export Factor NXF1 into Inclusion Bodies to Facilitate Viral Protein Expression,http://dx.doi.org/10.3390/cells9010187,PMC7017048,31940815,CC BY,"Ebola virus (EBOV) causes severe outbreaks of viral hemorrhagic fever in humans. While virus-host interactions are promising targets for antivirals, there is only limited knowledge regarding the interactions of EBOV with cellular host factors. Recently, we performed a genome-wide siRNA screen that identified the nuclear RNA export factor 1 (NXF1) as an important host factor for the EBOV life cycle. NXF1 is a major component of the nuclear mRNA export pathway that is usurped by many viruses whose life cycles include nuclear stages. However, the role of NXF1 in the life cycle of EBOV, a virus replicating in cytoplasmic inclusion bodies, remains unknown. In order to better understand the role of NXF1 in the EBOV life cycle, we performed a combination of co-immunoprecipitation and double immunofluorescence assays to characterize the interactions of NXF1 with viral proteins and RNAs. Additionally, using siRNA-mediated knockdown of NXF1 together with functional assays, we analyzed the role of NXF1 in individual aspects of the virus life cycle. With this approach we identified the EBOV nucleoprotein (NP) as a viral interaction partner of NXF1. Further studies revealed that NP interacts with the RNA-binding domain of NXF1 and competes with RNA for this interaction. Co-localization studies showed that RNA binding-deficient, but not wildtype NXF1, accumulates in NP-derived inclusion bodies, and knockdown experiments demonstrated that NXF1 is necessary for viral protein expression, but not for viral RNA synthesis. Finally, our results showed that NXF1 interacts with viral mRNAs, but not with viral genomic RNAs. Based on these results we suggest a model whereby NXF1 is recruited into inclusion bodies to promote the export of viral mRNA:NXF1 complexes from these sites. This would represent a novel function for NXF1 in the life cycle of cytoplasmically replicating viruses, and may provide a basis for new therapeutic approaches against EBOV, and possibly other emerging viruses.",2020 Jan 11,"['Wendt, Lisa', 'Brandt, Janine', 'Bodmer, Bianca S.', 'Reiche, Sven', 'Schmidt, Marie Luisa', 'Traeger, Shelby', 'Hoenen, Thomas']",Cells,,,False
5da7956e10ac1b78cc0fda6f4043ea034227459e,PMC,Annual and seasonal patterns in etiologies of pediatric community-acquired pneumonia due to respiratory viruses and Mycoplasma pneumoniae requiring hospitalization in South Korea,http://dx.doi.org/10.1186/s12879-020-4810-9,PMC7017508,32050912,CC BY,"BACKGROUND: Community–acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality. Its disease burden varies by age and etiology and is time dependent. We aimed to investigate the annual and seasonal patterns in etiologies of pediatric CAP requiring hospitalization. METHODS: We conducted a retrospective study in 30,994 children (aged 0–18 years) with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified as macrolide-sensitive MP, macrolide-less effective MP (MLEP), and macrolide-refractory MP (MRMP) based on fever duration after initiation of macrolide treatment, regardless of the results of in vitro macrolide sensitivity tests. RESULTS: MP and respiratory syncytial virus (RSV) were the two most commonly identified pathogens of CAP. With the two epidemics of MP pneumonia (2011 and 2015), the rates of clinical MLEP and MRMP pneumonia showed increasing trends of 36.4% of the total MP pneumonia. In children < 2 years of age, RSV (34.0%) was the most common cause of CAP, followed by MP (9.4%); however, MP was the most common cause of CAP in children aged 2–18 years of age (45.3%). Systemic corticosteroid was most commonly administered for MP pneumonia. The rate of hospitalization in intensive care units was the highest for RSV pneumonia, and ventilator care was most commonly needed in cases of adenovirus pneumonia. CONCLUSIONS: The present study provides fundamental data to establish public health policies to decrease the disease burden due to CAP and improve pediatric health.",2020 Feb 12,"['Lee, Eun', 'Kim, Chul-Hong', 'Lee, Yong Ju', 'Kim, Hyo-Bin', 'Kim, Bong-Seong', 'Kim, Hyung Young', 'Kim, Yunsun', 'Kim, Sangyoung', 'Park, Chorong', 'Seo, Ju-Hee', 'Sol, In Suk', 'Sung, Myongsoon', 'Song, Min Seob', 'Song, Dae Jin', 'Ahn, Young Min', 'Oh, Hea Lin', 'Yu, Jinho', 'Jung, Sungsu', 'Lee, Kyung Suk', 'Lee, Ju Suk', 'Jang, Gwang Cheon', 'Jang, Yoon-Young', 'Chung, Eun Hee', 'Chung, Hai Lee', 'Choi, Sung-Min', 'Choi, Yun Jung', 'Han, Man Yong', 'Shim, Jung Yeon', 'Kim, Jin Tack', 'Kim, Chang-Keun', 'Yang, Hyeon-Jong', None]",BMC Infect Dis,,,True
13307409d89468a48a81fca7621cbc7764b39d77,PMC,"Erratum: Vol. 69, No. 5",http://dx.doi.org/10.15585/mmwr.mm6906a5,PMC7017960,32053580,CC BY,,2020 Feb 14,"[None, None, 'Ahmed, Faruque', 'Almendares, Olivia', 'Belludi, Ashwin', 'Benowitz, Isaac', 'Braden, Chris', 'Carlson, Christina', 'Chiou, Howard', 'Clemmons, Nakia', 'Daigle, Dave', 'Desai, Meghna', 'Duca, Lindsey', 'Fischer, Marc', 'Ghinai, Isaac', 'Greene, Carolyn', 'Grigg, Cheri', 'Grills, Ardath', 'Grusich, Katherina', 'Hallowell, Benjamin', 'Hoff, Connor', 'Jacobs, Jesica', 'King, Bradley', 'MacArthur, John', 'Mattison, Claire', 'McDonald, Jason', 'McPherson, Tristan', 'Millman, Alexander', 'Novosad, Shannon', 'Pomeroy, Mary', 'Qualls, Noreen', 'Reynolds, Maryan', 'Rhodes, Heather', 'Sharma, Rajeev', 'Simmonds, Robert', 'Stewart, Rebekah', 'Sunenshine, Rebecca', 'Tenforde, Mark', 'Uzicanin, Amra', 'Verani, Jennifer', 'Whitehill, Florence', 'Wilson, Kathryn', 'Wortham, Jonathan']",MMWR Morb Mortal Wkly Rep,,,False
80a03c5cca3549c6bedad185f73950ce1213bf1b,PMC,"Persons Evaluated for 2019 Novel Coronavirus — United States, January 2020",http://dx.doi.org/10.15585/mmwr.mm6906e1,PMC7017962,32053579,CC BY,,2020 Feb 14,"['Bajema, Kristina L.', 'Oster, Alexandra M.', 'McGovern, Olivia L.', 'Lindstrom, Stephen', 'Stenger, Mark R.', 'Anderson, Tara C.', 'Isenhour,, Cheryl', 'Clarke, Kevin R.', 'Evans, Mary E.', 'Chu, Victoria T.', 'Biggs, Holly M.', 'Kirking, Hannah L.', 'Gerber, Susan I.', 'Hall, Aron J.', 'Fry, Alicia M.', 'Oliver, Sara E.', None, None, None, 'Abedi, Glen', 'Bower, William', 'Chatham-Stephens, Kevin', 'Conklin, Laura', 'Cooley, Laura', 'Cortese, Margaret', 'Curns, Aaron', 'Dooling, Kathleen', 'Gokhale, Runa', 'Gold, Jeremy', 'Grant, Gavin', 'Gutman, Julie', 'Hesse, Elisabeth', 'Kamili, Shifaq', 'Kim, Lindsay', 'Kirkcaldy, Robert', 'Koumans, Emily', 'Kujawski, Stephanie', 'Langley, Gayle', 'Lively, Joana', 'Lu, Xiaoyan', 'Lynch, Brian', 'Lyss, Sheryl', 'Malapati, Lakshmi', 'Martin, Michael', 'Mbaeyi, Sarah', 'McClung, Paul', 'Midgley, Claire', 'Miller, Maureen', 'Morales, Michelle', ""Murray, Janna'"", 'Parker Fiebelkorn, Amy', 'Patel, Manisha', 'Peacock, Georgina', 'Pierce, Taran', 'Rha, Brian', 'Sakthivel, Senthilkumar', 'Schneider, Eileen', 'Siegel, David A.', 'Sunshine, Brittany', 'Wallace, Megan', 'Wang, Lijuan', 'Watson, John', 'Whitaker, Brett', 'Yousaf, Anna']",MMWR Morb Mortal Wkly Rep,,,True
54a6d0d7afc568a29f625c33187e6800b0f72087,PMC,Both ADP-Ribosyl-Binding and Hydrolase Activities of the Alphavirus nsP3 Macrodomain Affect Neurovirulence in Mice,http://dx.doi.org/10.1128/mBio.03253-19,PMC7018654,32047134,CC BY,"Macrodomain (MD), a highly conserved protein fold present in a subset of plus-strand RNA viruses, binds to and hydrolyzes ADP-ribose (ADPr) from ADP-ribosylated proteins. ADPr-binding by the alphavirus nonstructural protein 3 (nsP3) MD is necessary for the initiation of virus replication in neural cells, whereas hydrolase activity facilitates replication complex amplification. To determine the importance of these activities for pathogenesis of alphavirus encephalomyelitis, mutations were introduced into the nsP3 MD of Sindbis virus (SINV), and the effects on ADPr binding and hydrolase activities, virus replication, immune responses, and disease were assessed. Elimination of ADPr-binding and hydrolase activities (G32E) severely impaired in vitro replication of SINV in neural cells and in vivo replication in the central nervous systems of 2-week-old mice with reversion to wild type (WT) (G) or selection of a less compromising change (S) during replication. SINVs with decreased binding and hydrolase activities (G32S and G32A) or with hydrolase deficiency combined with better ADPr-binding (Y114A) were less virulent than WT virus. Compared to the WT, the G32S virus replicated less well in both the brain and spinal cord, induced similar innate responses, and caused less severe disease with full recovery of survivors, whereas the Y114A virus replicated well, induced higher expression of interferon-stimulated and NF-κB-induced genes, and was cleared more slowly from the spinal cord with persistent paralysis in survivors. Therefore, MD function was important for neural cell replication both in vitro and in vivo and determined the outcome from alphavirus encephalomyelitis in mice.",2020 Feb 11,"['Abraham, Rachy', 'McPherson, Robert L.', 'Dasovich, Morgan', 'Badiee, Mohsen', 'Leung, Anthony K. L.', 'Griffin, Diane E.']",mBio,,,True
3fa90782b0cd99871663f5317bb69d255cfde50f,PMC,Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection,http://dx.doi.org/10.1128/mBio.02764-19,PMC7018658,32047128,CC BY,"Coronaviruses (CoVs) are common human and animal pathogens that can transmit zoonotically and cause severe respiratory disease syndromes. CoV infection requires spike proteins, which bind viruses to host cell receptors and catalyze virus-cell membrane fusion. Several CoV strains have spike proteins with two receptor-binding domains, an S1A that engages host sialic acids and an S1B that recognizes host transmembrane proteins. As this bivalent binding may enable broad zoonotic CoV infection, we aimed to identify roles for each receptor in distinct infection stages. Focusing on two betacoronaviruses, murine JHM-CoV and human Middle East respiratory syndrome coronavirus (MERS-CoV), we found that virus particle binding to cells was mediated by sialic acids; however, the transmembrane protein receptors were required for a subsequent virus infection. These results favored a two-step process in which viruses first adhere to sialic acids and then require subsequent engagement with protein receptors during infectious cell entry. However, sialic acids sufficiently facilitated the later stages of virus spread through cell-cell membrane fusion, without requiring protein receptors. This virus spread in the absence of the prototype protein receptors was increased by adaptive S1A mutations. Overall, these findings reveal roles for sialic acids in virus-cell binding, viral spike protein-directed cell-cell fusion, and resultant spread of CoV infections.",2020 Feb 11,"['Qing, Enya', 'Hantak, Michael', 'Perlman, Stanley', 'Gallagher, Tom']",mBio,,,True
23a2c32c86891deabe9176b41434f3ed202a5055,PMC,Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study,http://dx.doi.org/10.1038/s41413-020-0084-5,PMC7018717,32128276,CC BY,"The most severe sequelae after rehabilitation from SARS are femoral head necrosis and pulmonary fibrosis. We performed a 15-year follow-up on the lung and bone conditions of SARS patients. We evaluated the recovery from lung damage and femoral head necrosis in an observational cohort study of SARS patients using pulmonary CT scans, hip joint MRI examinations, pulmonary function tests and hip joint function questionnaires. Eighty medical staff contracted SARS in 2003. Two patients died of SARS, and 78 were enrolled in this study from August 2003 to March 2018. Seventy-one patients completed the 15-year follow-up. The percentage of pulmonary lesions on CT scans diminished from 2003 (9.40 ± 7.83)% to 2004 (3.20 ± 4.78)% (P < 0.001) and remained stable thereafter until 2018 (4.60 ± 6.37)%. Between 2006 and 2018, the proportion of patients with interstitial changes who had improved pulmonary function was lower than that of patients without lesions, as demonstrated by the one-second ratio (FEV(1)/FVC%, t = 2.21, P = 0.04) and mid-flow of maximum expiration (FEF(25%–75%), t = 2.76, P = 0.01). The volume of femoral head necrosis decreased significantly from 2003 (38.83 ± 21.01)% to 2005 (30.38 ± 20.23)% (P = 0.000 2), then declined slowly from 2005 to 2013 (28.99 ± 20.59)% and plateaued until 2018 (25.52 ± 15.51)%. Pulmonary interstitial damage and functional decline caused by SARS mostly recovered, with a greater extent of recovery within 2 years after rehabilitation. Femoral head necrosis induced by large doses of steroid pulse therapy in SARS patients was not progressive and was partially reversible.",2020 Feb 14,"['Zhang, Peixun', 'Li, Jia', 'Liu, Huixin', 'Han, Na', 'Ju, Jiabao', 'Kou, Yuhui', 'Chen, Lei', 'Jiang, Mengxi', 'Pan, Feng', 'Zheng, Yali', 'Gao, Zhancheng', 'Jiang, Baoguo']",Bone Res,,,True
bca258b97648522c7513be8ef70fdfd2ba5e3240,PMC,Large-scale Lassa fever outbreaks in Nigeria: quantifying the association between disease reproduction number and local rainfall,http://dx.doi.org/10.1017/S0950268819002267,PMC7019145,31918780,CC BY,"Lassa fever (LF) is increasingly recognised as an important rodent-borne viral haemorrhagic fever presenting a severe public health threat to sub-Saharan West Africa. In 2017–18, LF caused an unprecedented epidemic in Nigeria and the situation was worsening in 2018–19. This work aims to study the epidemiological features of epidemics in different Nigerian regions and quantify the association between reproduction number (R) and state rainfall. We quantify the infectivity of LF by the reproduction numbers estimated from four different growth models: the Richards, three-parameter logistic, Gompertz and Weibull growth models. LF surveillance data are used to fit the growth models and estimate the Rs and epidemic turning points (τ) in different regions at different time periods. Cochran's Q test is further applied to test the spatial heterogeneity of the LF epidemics. A linear random-effect regression model is adopted to quantify the association between R and state rainfall with various lag terms. Our estimated Rs for 2017–18 (1.33 with 95% CI 1.29–1.37) was significantly higher than those for 2016–17 (1.23 with 95% CI: (1.22, 1.24)) and 2018–19 (ranged from 1.08 to 1.36). We report spatial heterogeneity in the Rs for epidemics in different Nigerian regions. We find that a one-unit (mm) increase in average monthly rainfall over the past 7 months could cause a 0.62% (95% CI 0.20%–1.05%)) rise in R. There is significant spatial heterogeneity in the LF epidemics in different Nigerian regions. We report clear evidence of rainfall impacts on LF epidemics in Nigeria and quantify the impact.",,"['Zhao, Shi', 'Musa, Salihu S.', 'Fu, Hao', 'He, Daihai', 'Qin, Jing']",Epidemiol Infect.; 148:e4,,,True
c21a1e8e2ba8c0faa92fede77b7976f6f1061716,PMC,A Tale of Two Viruses: The Distinct Spike Glycoproteins of Feline Coronaviruses,http://dx.doi.org/10.3390/v12010083,PMC7019228,31936749,CC BY,"Feline coronavirus (FCoV) is a complex viral agent that causes a variety of clinical manifestations in cats, commonly known as feline infectious peritonitis (FIP). It is recognized that FCoV can occur in two different serotypes. However, differences in the S protein are much more than serological or antigenic variants, resulting in the effective presence of two distinct viruses. Here, we review the distinct differences in the S proteins of these viruses, which are likely to translate into distinct biological outcomes. We introduce a new concept related to the non-taxonomical classification and differentiation among FCoVs by analyzing and comparing the genetic, structural, and functional characteristics of FCoV and the FCoV S protein among the two serotypes and FCoV biotypes. Based on our analysis, we suggest that our understanding of FIP needs to consider whether the presence of these two distinct viruses has implications in clinical settings.",2020 Jan 10,"['Jaimes, Javier A.', 'Millet, Jean K.', 'Stout, Alison E.', 'André, Nicole M.', 'Whittaker, Gary R.']",Viruses,,,True
2f2afad5760ec1b8e76725302e58239863c540ad,PMC,A Tale of Two Viruses: The Distinct Spike Glycoproteins of Feline Coronaviruses,http://dx.doi.org/10.3390/v12010083,PMC7019228,31936749,CC BY,"Feline coronavirus (FCoV) is a complex viral agent that causes a variety of clinical manifestations in cats, commonly known as feline infectious peritonitis (FIP). It is recognized that FCoV can occur in two different serotypes. However, differences in the S protein are much more than serological or antigenic variants, resulting in the effective presence of two distinct viruses. Here, we review the distinct differences in the S proteins of these viruses, which are likely to translate into distinct biological outcomes. We introduce a new concept related to the non-taxonomical classification and differentiation among FCoVs by analyzing and comparing the genetic, structural, and functional characteristics of FCoV and the FCoV S protein among the two serotypes and FCoV biotypes. Based on our analysis, we suggest that our understanding of FIP needs to consider whether the presence of these two distinct viruses has implications in clinical settings.",2020 Jan 10,"['Jaimes, Javier A.', 'Millet, Jean K.', 'Stout, Alison E.', 'André, Nicole M.', 'Whittaker, Gary R.']",Viruses,,,False
6049f1c151fa95bc40deaf050225dd7a00880171,PMC,Development of a Multiplex RT-qPCR for the Detection of Different Clades of Avian Influenza in Poultry,http://dx.doi.org/10.3390/v12010100,PMC7019278,31952218,CC BY,"Since the initial detection of H5N1, a highly pathogenic avian influenza (HPAI) virus, in 1996 in China, numerous HPAI H5 lineages have been classified, and they continue to pose a threat to animal and human health. In this study, we developed a novel primer/probe set that can be employed to simultaneously detect pan-H5 HPAI and two clades, 2.3.2.1 and 2.3.4.4, of H5Nx viruses using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The sensitivity and specificity of these primer sets and probes were confirmed with a number of different subtypes of influenza virus and the H5-HA gene plasmid DNA. In particular, the multiplex RT-qPCR assay was successfully applied to the simultaneous detection of H5 HPAI and different virus clades in clinical field samples from a poultry farm. Therefore, this multiplex assay and a novel detection primer set and probes will be useful for the laboratory diagnosis and epidemiological field studies of different circulating H5 HPAI virus clades in poultry and migratory wild birds.",2020 Jan 15,"['Le, Tran Bac', 'Kim, Hye Kwon', 'Na, Woonsung', 'Le, Van Phan', 'Song, Min-Suk', 'Song, Daesub', 'Jeong, Dae Gwin', 'Yoon, Sun-Woo']",Viruses,,,True
246d1372657ab63d6f10a57907fcda07c1ddbc3a,PMC,Virus Metagenomics in Farm Animals: A Systematic Review,http://dx.doi.org/10.3390/v12010107,PMC7019290,31963174,CC BY,"A majority of emerging infectious diseases are of zoonotic origin. Metagenomic Next-Generation Sequencing (mNGS) has been employed to identify uncommon and novel infectious etiologies and characterize virus diversity in human, animal, and environmental samples. Here, we systematically reviewed studies that performed viral mNGS in common livestock (cattle, small ruminants, poultry, and pigs). We identified 2481 records and 120 records were ultimately included after a first and second screening. Pigs were the most frequently studied livestock and the virus diversity found in samples from poultry was the highest. Known animal viruses, zoonotic viruses, and novel viruses were reported in available literature, demonstrating the capacity of mNGS to identify both known and novel viruses. However, the coverage of metagenomic studies was patchy, with few data on the virome of small ruminants and respiratory virome of studied livestock. Essential metadata such as age of livestock and farm types were rarely mentioned in available literature, and only 10.8% of the datasets were publicly available. Developing a deeper understanding of livestock virome is crucial for detection of potential zoonotic and animal pathogens and One Health preparedness. Metagenomic studies can provide this background but only when combined with essential metadata and following the “FAIR” (Findable, Accessible, Interoperable, and Reusable) data principles.",2020 Jan 16,"['Kwok, Kirsty T. T.', 'Nieuwenhuijse, David F.', 'Phan, My V. T.', 'Koopmans, Marion P. G.']",Viruses,,,True
63f58030dbe7e46d82ccf7794885cac6a912351f,PMC,Virus Metagenomics in Farm Animals: A Systematic Review,http://dx.doi.org/10.3390/v12010107,PMC7019290,31963174,CC BY,"A majority of emerging infectious diseases are of zoonotic origin. Metagenomic Next-Generation Sequencing (mNGS) has been employed to identify uncommon and novel infectious etiologies and characterize virus diversity in human, animal, and environmental samples. Here, we systematically reviewed studies that performed viral mNGS in common livestock (cattle, small ruminants, poultry, and pigs). We identified 2481 records and 120 records were ultimately included after a first and second screening. Pigs were the most frequently studied livestock and the virus diversity found in samples from poultry was the highest. Known animal viruses, zoonotic viruses, and novel viruses were reported in available literature, demonstrating the capacity of mNGS to identify both known and novel viruses. However, the coverage of metagenomic studies was patchy, with few data on the virome of small ruminants and respiratory virome of studied livestock. Essential metadata such as age of livestock and farm types were rarely mentioned in available literature, and only 10.8% of the datasets were publicly available. Developing a deeper understanding of livestock virome is crucial for detection of potential zoonotic and animal pathogens and One Health preparedness. Metagenomic studies can provide this background but only when combined with essential metadata and following the “FAIR” (Findable, Accessible, Interoperable, and Reusable) data principles.",2020 Jan 16,"['Kwok, Kirsty T. T.', 'Nieuwenhuijse, David F.', 'Phan, My V. T.', 'Koopmans, Marion P. G.']",Viruses,,,True
8dad44cafa563c90b07152ef2038e530b19edb31,PMC,E3 Ligase ITCH Interacts with the Z Matrix Protein of Lassa and Mopeia Viruses and Is Required for the Release of Infectious Particles,http://dx.doi.org/10.3390/v12010049,PMC7019300,31906112,CC BY,"Lassa virus (LASV) and Mopeia virus (MOPV) are two closely related, rodent-born mammarenaviruses. LASV is the causative agent of Lassa fever, a deadly hemorrhagic fever endemic in West Africa, whereas MOPV is non-pathogenic in humans. The Z matrix protein of arenaviruses is essential to virus assembly and budding by recruiting host factors, a mechanism that remains partially defined. To better characterize the interactions involved, a yeast two-hybrid screen was conducted using the Z proteins from LASV and MOPV as a bait. The cellular proteins ITCH and WWP1, two members of the Nedd4 family of HECT E3 ubiquitin ligases, were found to bind the Z proteins of LASV, MOPV and other arenaviruses. The PPxY late-domain motif of the Z proteins is required for the interaction with ITCH, although the E3 ubiquitin-ligase activity of ITCH is not involved in Z ubiquitination. The silencing of ITCH was shown to affect the replication of the old-world mammarenaviruses LASV, MOPV, Lymphocytic choriomeningitis virus (LCMV) and to a lesser extent Lujo virus (LUJV). More precisely, ITCH was involved in the egress of virus-like particles and the release of infectious progeny viruses. Thus, ITCH constitutes a novel interactor of LASV and MOPV Z proteins that is involved in virus assembly and release.",2019 Dec 31,"['Baillet, Nicolas', 'Krieger, Sophie', 'Carnec, Xavier', 'Mateo, Mathieu', 'Journeaux, Alexandra', 'Merabet, Othmann', 'Caro, Valérie', 'Tangy, Frédéric', 'Vidalain, Pierre-Olivier', 'Baize, Sylvain']",Viruses,,,True
95cd65dbf317e24c13557dbf46ffbaa4c206f8be,PMC,Isolation and Identification of Porcine Deltacoronavirus and Alteration of Immunoglobulin Transport Receptors in the Intestinal Mucosa of PDCoV-Infected Piglets,http://dx.doi.org/10.3390/v12010079,PMC7019308,31936476,CC BY,"Porcine deltacoronavirus (PDCoV) is a porcine enteropathogenic coronavirus that causes watery diarrhea, vomiting, and frequently death in piglets, causing serious economic losses to the pig industry. The strain CHN-JS-2017 was isolated and identified by cytopathology, immunofluorescence assays, transmission electron microscopy, and sequence analysis. A nucleotide sequence alignment showed that the whole genome of CHN-JS-2017 is 97.4%–99.6% identical to other PDCoV strains. The pathogenicity of the CHN-JS-2017 strain was investigated in orally inoculated five-day-old piglets; the piglets developed acute, watery diarrhea, but all recovered and survived. CHN-JS-2017 infection-induced microscopic lesions were observed, and viral antigens were detected mainly by immunohistochemical staining in the small intestine. The neonatal Fc receptor (FcRn) and polymeric immunoglobulin receptor (pIgR) are crucial immunoglobulin (Ig) receptors for the transcytosis ofimmunoglobulin G (IgG), IgA, or IgM. Importantly, CHN-JS-2017 infected five-day-old piglets could significantly down-regulate the expression of FcRn, pIgR, and nuclear factor-kappa B (NF-κB)in the intestinal mucosa. Note that the level of FcRn mRNA in the intestinal mucosa of normal piglets is positively correlated with pIgR and NF-κB. At the same time, the expressions of FcRn, pIgR, and NF-κB mRNA are also positively correlated in infected piglets. These results may help explain the immunological and pathological changes associated with porcine deltacorononirus infection.",2020 Jan 9,"['Qian, Shaoju', 'Jia, Xiangchao', 'Gao, Zitong', 'Zhang, Weida', 'Xu, Qingrong', 'Li, Zili']",Viruses,,,True
7c8fb34411d0ad519167d3940a1f738dcd34d19c,PMC,Isolation and Identification of Porcine Deltacoronavirus and Alteration of Immunoglobulin Transport Receptors in the Intestinal Mucosa of PDCoV-Infected Piglets,http://dx.doi.org/10.3390/v12010079,PMC7019308,31936476,CC BY,"Porcine deltacoronavirus (PDCoV) is a porcine enteropathogenic coronavirus that causes watery diarrhea, vomiting, and frequently death in piglets, causing serious economic losses to the pig industry. The strain CHN-JS-2017 was isolated and identified by cytopathology, immunofluorescence assays, transmission electron microscopy, and sequence analysis. A nucleotide sequence alignment showed that the whole genome of CHN-JS-2017 is 97.4%–99.6% identical to other PDCoV strains. The pathogenicity of the CHN-JS-2017 strain was investigated in orally inoculated five-day-old piglets; the piglets developed acute, watery diarrhea, but all recovered and survived. CHN-JS-2017 infection-induced microscopic lesions were observed, and viral antigens were detected mainly by immunohistochemical staining in the small intestine. The neonatal Fc receptor (FcRn) and polymeric immunoglobulin receptor (pIgR) are crucial immunoglobulin (Ig) receptors for the transcytosis ofimmunoglobulin G (IgG), IgA, or IgM. Importantly, CHN-JS-2017 infected five-day-old piglets could significantly down-regulate the expression of FcRn, pIgR, and nuclear factor-kappa B (NF-κB)in the intestinal mucosa. Note that the level of FcRn mRNA in the intestinal mucosa of normal piglets is positively correlated with pIgR and NF-κB. At the same time, the expressions of FcRn, pIgR, and NF-κB mRNA are also positively correlated in infected piglets. These results may help explain the immunological and pathological changes associated with porcine deltacorononirus infection.",2020 Jan 9,"['Qian, Shaoju', 'Jia, Xiangchao', 'Gao, Zitong', 'Zhang, Weida', 'Xu, Qingrong', 'Li, Zili']",Viruses,,,False
8607aac9046864becdec9a89df48524d61192e09,PMC,A Soluble Version of Nipah Virus Glycoprotein G Delivered by Vaccinia Virus MVA Activates Specific CD8 and CD4 T Cells in Mice,http://dx.doi.org/10.3390/v12010026,PMC7019319,31878180,CC BY,"Nipah virus (NiV) is an emerging zoonotic virus that is transmitted by bats to humans and to pigs, causing severe respiratory disease and often fatal encephalitis. Antibodies directed against the NiV-glycoprotein (G) protein are known to play a major role in clearing NiV infection and in providing vaccine-induced protective immunity. More recently, T cells have been also shown to be involved in recovery from NiV infection. So far, relatively little is known about the role of T cell responses and the antigenic targets of NiV-G that are recognized by CD8 T cells. In this study, NiV-G protein served as the target immunogen to activate NiV-specific cellular immune responses. Modified Vaccinia virus Ankara (MVA), a safety-tested strain of vaccinia virus for preclinical and clinical vaccine research, was used for the generation of MVA–NiV-G candidate vaccines expressing different versions of recombinant NiV-G. Overlapping peptides covering the entire NiV-G protein were used to identify major histocompatibility complex class I/II-restricted T cell responses in type I interferon receptor-deficient (IFNAR−/−) mice after vaccination with the MVA–NiV-G candidate vaccines. We have identified an H2-b-restricted nonamer peptide epitope with CD8 T cell antigenicity and a H2-b 15mer with CD4 T cell antigenicity in the NiV-G protein. The identification of this epitope and the availability of the MVA–NiV-G candidate vaccines will help to evaluate NiV-G-specific immune responses and the potential immune correlates of vaccine-mediated protection in the appropriate murine models of NiV-G infection. Of note, a soluble version of NiV-G was advantageous in activating NiV-G-specific cellular immune responses using these peptides.",2019 Dec 24,"['Kalodimou, Georgia', 'Veit, Svenja', 'Jany, Sylvia', 'Kalinke, Ulrich', 'Broder, Christopher C.', 'Sutter, Gerd', 'Volz, Asisa']",Viruses,,,True
bb40bca4ee06eacfdf5f055cbaf09a54a2f54aff,PMC,Epidemiology and Clinical Characteristics of Influenza C Virus,http://dx.doi.org/10.3390/v12010089,PMC7019359,31941041,CC BY,"Influenza C virus (ICV) is a common yet under-recognized cause of acute respiratory illness. ICV seropositivity has been found to be as high as 90% by 7–10 years of age, suggesting that most people are exposed to ICV at least once during childhood. Due to difficulty detecting ICV by cell culture, epidemiologic studies of ICV likely have underestimated the burden of ICV infection and disease. Recent development of highly sensitive RT-PCR has facilitated epidemiologic studies that provide further insights into the prevalence, seasonality, and course of ICV infection. In this review, we summarize the epidemiology and clinical characteristics of ICV.",2020 Jan 13,"['Sederdahl, Bethany K.', 'Williams, John V.']",Viruses,,,True
bc763a4c1cb0175d61d1332af8d137d0482df73b,PMC,When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses,http://dx.doi.org/10.3390/v12010008,PMC7019426,31861617,CC BY,"Dendritic cells (DCs) are among the first cells that recognize incoming viruses at the mucosal portals of entry. Initial interaction between DCs and viruses facilitates cell activation and migration to secondary lymphoid tissues, where these antigen presenting cells (APCs) prime specific adaptive immune responses. Some viruses, however, have evolved strategies to subvert the migratory capacity of DCs as a way to disseminate infection systemically. Here we focus on the role of Siglec-1, a sialic acid-binding type I lectin receptor potently upregulated by type I interferons on DCs, that acts as a double edge sword, containing viral replication through the induction of antiviral immunity, but also favoring viral spread within tissues. Such is the case for distant enveloped viruses like human immunodeficiency virus (HIV)-1 or Ebola virus (EBOV), which incorporate sialic acid-containing gangliosides on their viral membrane and are effectively recognized by Siglec-1. Here we review how Siglec-1 is highly induced on the surface of human DCs upon viral infection, the way this impacts different antigen presentation pathways, and how enveloped viruses have evolved to exploit these APC functions as a potent dissemination strategy in different anatomical compartments.",2019 Dec 19,"['Perez-Zsolt, Daniel', 'Martinez-Picado, Javier', 'Izquierdo-Useros, Nuria']",Viruses,,,True
7151947d17c83f7764b115d4e21a982738bb12f6,PMC,Loop-Mediated Isothermal Amplification (LAMP) for the Diagnosis of Zika Virus: A Review,http://dx.doi.org/10.3390/v12010019,PMC7019470,31877989,CC BY,"The recent outbreak of Zika virus (ZIKV) in the Americas and its devastating developmental and neurological manifestations has prompted the development of field-based diagnostics that are rapid, reliable, handheld, specific, sensitive, and inexpensive. The gold standard molecular method for lab-based diagnosis of ZIKV, from either patient samples or insect vectors, is reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The method, however, is costly and requires lab-based equipment and expertise, which severely limits its use as a point-of-care (POC) tool in resource-poor settings. Moreover, given the lack of antivirals or approved vaccines for ZIKV infection, a POC diagnostic test is urgently needed for the early detection of new outbreaks and to adequately manage patients. Loop-mediated isothermal amplification (LAMP) is a compelling alternative to RT-qPCR for ZIKV and other arboviruses. This low-cost molecular system can be freeze-dried for distribution and exhibits high specificity, sensitivity, and efficiency. A growing body of evidence suggests that LAMP assays can provide greater accessibility to much-needed diagnostics for ZIKV infections, especially in developing countries where the ZIKV is now endemic. This review summarizes the different LAMP methods that have been developed for the virus and summarizes their features, advantages, and limitations.",2019 Dec 23,"['da Silva, Severino Jefferson Ribeiro', 'Pardee, Keith', 'Pena, Lindomar']",Viruses,,,True
ed22ff950ded9997b793e0cc610c7228fb57e7bb,PMC,Usefulness of Clinical Definitions of Influenza for Public Health Surveillance Purposes,http://dx.doi.org/10.3390/v12010095,PMC7019582,31947696,CC BY,"This study investigated the performance of various case definitions and influenza symptoms in a primary healthcare sentinel surveillance system. A retrospective study of the clinical and epidemiological characteristics of the cases reported by a primary healthcare sentinel surveillance network for eleven years in Catalonia was conducted. Crude and adjusted diagnostic odds ratios (aDORs) and 95% confidence intervals (CIs) of the case definitions and symptoms for all weeks and epidemic weeks were estimated. The most predictive case definition for laboratory-confirmed influenza was the World Health Organization (WHO) case definition for ILI in all weeks (aDOR 2.69; 95% CI 2.42–2.99) and epidemic weeks (aDOR 2.20; 95% CI 1.90–2.54). The symptoms that were significant positive predictors for confirmed influenza were fever, cough, myalgia, headache, malaise, and sudden onset. Fever had the highest aDOR in all weeks (4.03; 95% CI 3.38–4.80) and epidemic weeks (2.78; 95% CI 2.21–3.50). All of the case definitions assessed performed better in patients with comorbidities than in those without. The performance of symptoms varied by age groups, with fever being of high value in older people, and cough being of high value in children. In patients with comorbidities, the performance of fever was the highest (aDOR 5.45; 95% CI 3.43–8.66). No differences in the performance of the case definition or symptoms in influenza cases according to virus type were found.",2020 Jan 14,"['Domínguez, Àngela', 'Soldevila, Núria', 'Torner, Núria', 'Martínez, Ana', 'Godoy, Pere', 'Rius, Cristina', 'Jané, Mireia', None]",Viruses,,,True
ce248b901191d45f3e56f1e6664a0239738aa148,PMC,Discovery and Prevalence of Divergent RNA Viruses in European Field Voles and Rabbits,http://dx.doi.org/10.3390/v12010047,PMC7019641,31906044,CC BY,"The advent of unbiased metagenomic virus discovery has revolutionized studies of virus biodiversity and evolution. Despite this, our knowledge of the virosphere, including in mammalian species, remains limited. We used unbiased metagenomic sequencing to identify RNA viruses in European field voles and rabbits. Accordingly, we identified a number of novel RNA viruses including astrovirus, rotavirus A, picorna-like virus and a narmovirus (paramyxovirus). In addition, we identified a sobemovirus and a novel luteovirus that likely originated from the rabbit diet. These newly discovered viruses were often divergent from those previously described. The novel astrovirus was most closely related to a virus sampled from the rodent-eating European roller bird (Coracias garrulous). PCR screening revealed that the novel narmovirus in the UK field vole had a prevalence of approximately 4%, and shared common ancestry with other rodent narmoviruses sampled globally. Two novel rotavirus A sequences were detected in a UK field vole and a French rabbit, the latter with a prevalence of 5%. Finally, a highly divergent picorna-like virus found in the gut of the French rabbit virus was only ~35% similar to an arilivirus at the amino acid level, suggesting the presence of a novel viral genus within the Picornaviridae.",2019 Dec 31,"['Tsoleridis, Theocharis', 'Chappell, Joseph G.', 'Monchatre-Leroy, Elodie', 'Umhang, Gérald', 'Shi, Mang', 'Bennett, Malcolm', 'Tarlinton, Rachael E.', 'McClure, C. Patrick', 'Holmes, Edward C.', 'Ball, Jonathan K.']",Viruses,,,True
3b999c895074ebfdd61b3f98e0eb6de1daa725a6,PMC,Discovery and Prevalence of Divergent RNA Viruses in European Field Voles and Rabbits,http://dx.doi.org/10.3390/v12010047,PMC7019641,31906044,CC BY,"The advent of unbiased metagenomic virus discovery has revolutionized studies of virus biodiversity and evolution. Despite this, our knowledge of the virosphere, including in mammalian species, remains limited. We used unbiased metagenomic sequencing to identify RNA viruses in European field voles and rabbits. Accordingly, we identified a number of novel RNA viruses including astrovirus, rotavirus A, picorna-like virus and a narmovirus (paramyxovirus). In addition, we identified a sobemovirus and a novel luteovirus that likely originated from the rabbit diet. These newly discovered viruses were often divergent from those previously described. The novel astrovirus was most closely related to a virus sampled from the rodent-eating European roller bird (Coracias garrulous). PCR screening revealed that the novel narmovirus in the UK field vole had a prevalence of approximately 4%, and shared common ancestry with other rodent narmoviruses sampled globally. Two novel rotavirus A sequences were detected in a UK field vole and a French rabbit, the latter with a prevalence of 5%. Finally, a highly divergent picorna-like virus found in the gut of the French rabbit virus was only ~35% similar to an arilivirus at the amino acid level, suggesting the presence of a novel viral genus within the Picornaviridae.",2019 Dec 31,"['Tsoleridis, Theocharis', 'Chappell, Joseph G.', 'Monchatre-Leroy, Elodie', 'Umhang, Gérald', 'Shi, Mang', 'Bennett, Malcolm', 'Tarlinton, Rachael E.', 'McClure, C. Patrick', 'Holmes, Edward C.', 'Ball, Jonathan K.']",Viruses,,,False
8c9c650f233ed3a031c995a887d8dfbc8b41e78c,PMC,Feline Infectious Peritonitis Virus Nsp5 Inhibits Type I Interferon Production by Cleaving NEMO at Multiple Sites,http://dx.doi.org/10.3390/v12010043,PMC7019732,31905881,CC BY,"Feline infectious peritonitis (FIP), caused by virulent feline coronavirus, is the leading infectious cause of death in cats. The type I interferon (type I IFN)-mediated immune responses provide host protection from infectious diseases. Several coronaviruses have been reported to evolve diverse strategies to evade host IFN response. However, whether feline infectious peritonitis virus (FIPV) antagonizes the type I IFN signaling remains unclear. In this study, we demonstrated that FIPV strain DF2 infection not only failed to induce interferon-β (IFN-β) and interferon-stimulated gene (ISG) production, but also inhibited Sendai virus (SEV) or polyinosinic-polycytidylic acid (poly(I:C))-induced IFN-β production. Subsequently, we found that one of the non-structural proteins encoded by the FIPV genome, nsp5, interrupted type I IFN signaling in a protease-dependent manner by cleaving the nuclear factor κB (NF-κB) essential modulator (NEMO) at three sites—glutamine132 (Q132), Q205, and Q231. Further investigation revealed that the cleavage products of NEMO lost the ability to activate the IFN-β promoter. Mechanistically, the nsp5-mediated NEMO cleavage disrupted the recruitment of the TRAF family member-associated NF-κB activator (TANK) to NEMO, which reduced the phosphorylation of interferon regulatory factor 3 (IRF3), leading to the inhibition of type I IFN production. Our research provides new insights into the mechanism for FIPV to counteract host innate immune response.",2019 Dec 30,"['Chen, Si', 'Tian, Jin', 'Li, Zhijie', 'Kang, Hongtao', 'Zhang, Jikai', 'Huang, Jiapei', 'Yin, Hang', 'Hu, Xiaoliang', 'Qu, Liandong']",Viruses,,,True
f51b986600acc015fa48820a1ec11c90ea871d6d,PMC,Interferon-Gamma Modulation of the Local T Cell Response to Alphavirus Encephalomyelitis,http://dx.doi.org/10.3390/v12010113,PMC7019780,31963302,CC BY,"Infection of mice with Sindbis virus (SINV) provides a model for examining the role of the immune response to alphavirus infection of the central nervous system (CNS). Interferon-gamma (IFN-γ) is an important component of this response, and we show that SINV-infected differentiated neurons respond to IFN-γ in vitro by induction of antiviral genes and suppression of virus replication. To determine the in vivo effects of IFN-γ on SINV clearance and T cell responses, C57BL/6 mice lacking IFN-γ or IFN-γ receptor-1 were compared to wild-type (WT) mice after intracranial SINV infection. In WT mice, IFN-γ was first produced in the CNS by natural killer cells and then by CD4(+) and CD8(+) T cells. Mice with impaired IFN-γ signaling initiated clearance of viral RNA earlier than WT mice associated with CNS entry of more granzyme B-producing CD8(+) T cells. However, these mice established fewer CD8(+) tissue-resident memory T (T(RM)) cells and were more likely to experience reactivation of viral RNA synthesis late after infection. Therefore, IFN-γ suppresses the local development of granzyme B-expressing CD8(+) T cells and slows viral RNA clearance but promotes CD8(+) T(RM) cell establishment.",2020 Jan 16,"['Baxter, Victoria K.', 'Griffin, Diane E.']",Viruses,,,True
1a7d600387654c0315c076f74d8479adb4403d75,PMC,Photonic Crystal Nanobeam Cavities for Nanoscale Optical Sensing: A Review,http://dx.doi.org/10.3390/mi11010072,PMC7019810,31936559,CC BY,"The ability to detect nanoscale objects is particular crucial for a wide range of applications, such as environmental protection, early-stage disease diagnosis and drug discovery. Photonic crystal nanobeam cavity (PCNC) sensors have attracted great attention due to high-quality factors and small-mode volumes (Q/V) and good on-chip integrability with optical waveguides/circuits. In this review, we focus on nanoscale optical sensing based on PCNC sensors, including ultrahigh figure of merit (FOM) sensing, single nanoparticle trapping, label-free molecule detection and an integrated sensor array for multiplexed sensing. We believe that the PCNC sensors featuring ultracompact footprint, high monolithic integration capability, fast response and ultrahigh sensitivity sensing ability, etc., will provide a promising platform for further developing lab-on-a-chip devices for biosensing and other functionalities.",2020 Jan 9,"['Yang, Da-Quan', 'Duan, Bing', 'Liu, Xiao', 'Wang, Ai-Qiang', 'Li, Xiao-Gang', 'Ji, Yue-Feng']",Micromachines (Basel),,,True
4393d1b0e0262247c9c6ace6ebda9dcd5395d6fa,PMC,Investigation of the Role of the Spike Protein in Reversing the Virulence of the Highly Virulent Taiwan Porcine Epidemic Diarrhea Virus Pintung 52 Strains and Its Attenuated Counterpart,http://dx.doi.org/10.3390/v12010041,PMC7019868,31905842,CC BY,"Porcine epidemic diarrhea virus (PEDV) has continuously caused severe economic losses to the global swine industries; however, no successful vaccine against PEDV has been developed. In this study, we generated four autologous recombinant viruses, including the highly virulent iPEDVPT-P5, attenuated iPEDVPT-P96, and two chimeric viruses (iPEDVPT-P5-96S and iPEDVPT-P96-5S) with the reciprocally exchanged spike (S) gene, to study the role of the S gene in PEDV pathogenesis. A deeper understanding of PEDV attenuation will aid in the rational design of a live attenuated vaccine (LAV) using reverse genetics system. Our results showed that replacing the S gene from the highly virulent iPEDVPT-P5 led to complete restoration of virulence of the attenuated iPEDVPT-P96, with nearly identical viral shedding, diarrhea pattern, and mortality rate as the parental iPEDVPT-P5. In contrast, substitution of the S gene with that from the attenuated iPEDVPT-P96 resulted in partial attenuation of iPEDVPT-P5, exhibiting similar viral shedding and diarrhea patterns as the parental iPEDVPT-P96 with slightly severe histological lesions and higher mortality rate. Collectively, our data confirmed that the attenuation of the PEDVPT-P96 virus is primarily attributed to mutations in the S gene. However, mutation in S gene alone could not fully attenuate the virulence of iPEDVPT-P5. Gene (s) other than S gene might also play a role in determining virulence.",2019 Dec 30,"['Kao, Chi-Fei', 'Chang, Hui-Wen']",Viruses,,,True
dd0d9655d869cdb29694ca2d45fbf443f77a2d74,PMC,Investigation of the Role of the Spike Protein in Reversing the Virulence of the Highly Virulent Taiwan Porcine Epidemic Diarrhea Virus Pintung 52 Strains and Its Attenuated Counterpart,http://dx.doi.org/10.3390/v12010041,PMC7019868,31905842,CC BY,"Porcine epidemic diarrhea virus (PEDV) has continuously caused severe economic losses to the global swine industries; however, no successful vaccine against PEDV has been developed. In this study, we generated four autologous recombinant viruses, including the highly virulent iPEDVPT-P5, attenuated iPEDVPT-P96, and two chimeric viruses (iPEDVPT-P5-96S and iPEDVPT-P96-5S) with the reciprocally exchanged spike (S) gene, to study the role of the S gene in PEDV pathogenesis. A deeper understanding of PEDV attenuation will aid in the rational design of a live attenuated vaccine (LAV) using reverse genetics system. Our results showed that replacing the S gene from the highly virulent iPEDVPT-P5 led to complete restoration of virulence of the attenuated iPEDVPT-P96, with nearly identical viral shedding, diarrhea pattern, and mortality rate as the parental iPEDVPT-P5. In contrast, substitution of the S gene with that from the attenuated iPEDVPT-P96 resulted in partial attenuation of iPEDVPT-P5, exhibiting similar viral shedding and diarrhea patterns as the parental iPEDVPT-P96 with slightly severe histological lesions and higher mortality rate. Collectively, our data confirmed that the attenuation of the PEDVPT-P96 virus is primarily attributed to mutations in the S gene. However, mutation in S gene alone could not fully attenuate the virulence of iPEDVPT-P5. Gene (s) other than S gene might also play a role in determining virulence.",2019 Dec 30,"['Kao, Chi-Fei', 'Chang, Hui-Wen']",Viruses,,,False
2530bf775255e8026438e91645aba95d0506928e,PMC,A Chimeric Sudan Virus-Like Particle Vaccine Candidate Produced by a Recombinant Baculovirus System Induces Specific Immune Responses in Mice and Horses,http://dx.doi.org/10.3390/v12010064,PMC7019897,31947873,CC BY,"Ebola virus infections lead to severe hemorrhagic fevers in humans and nonhuman primates; and human fatality rates are as high as 67%–90%. Since the Ebola virus was discovered in 1976, the only available treatments have been medical support or the emergency administration of experimental drugs. The absence of licensed vaccines and drugs against the Ebola virus impedes the prevention of viral infection. In this study, we generated recombinant baculoviruses (rBV) expressing the Sudan virus (SUDV) matrix structural protein (VP40) (rBV-VP40-VP40) or the SUDV glycoprotein (GP) (rBV-GP-GP), and SUDV virus-like particles (VLPs) were produced by co-infection of Sf9 cells with rBV-SUDV-VP40 and rBV-SUDV-GP. The expression of SUDV VP40 and GP in SUDV VLPs was demonstrated by IFA and Western blot analysis. Electron microscopy results demonstrated that SUDV VLPs had a filamentous morphology. The immunogenicity of SUDV VLPs produced in insect cells was evaluated by the immunization of mice. The analysis of antibody responses showed that mice vaccinated with SUDV VLPs and the adjuvant Montanide ISA 201 produced SUDV GP-specific IgG antibodies. Sera from SUDV VLP-immunized mice were able to block infection by SUDV GP pseudotyped HIV, indicating that a neutralizing antibody against the SUDV GP protein was produced. Furthermore, the activation of B cells in the group immunized with VLPs mixed with Montanide ISA 201 was significant one week after the primary immunization. Vaccination with the SUDV VLPs markedly increased the frequency of antigen-specific cells secreting type 1 and type 2 cytokines. To study the therapeutic effects of SUDV antibodies, horses were immunized with SUDV VLPs emulsified in Freund’s complete adjuvant or Freund’s incomplete adjuvant. The results showed that horses could produce SUDV GP-specific antibodies and neutralizing antibodies. These results showed that SUDV VLPs demonstrate excellent immunogenicity and represent a promising approach for vaccine development against SUDV infection. Further, these horse anti-SUDV purified immunoglobulins lay a foundation for SUDV therapeutic drug research.",2020 Jan 3,"['Wu, Fangfang', 'Zhang, Shengnan', 'Zhang, Ying', 'Mo, Ruo', 'Yan, Feihu', 'Wang, Hualei', 'Wong, Gary', 'Chi, Hang', 'Wang, Tiecheng', 'Feng, Na', 'Gao, Yuwei', 'Xia, Xianzhu', 'Zhao, Yongkun', 'Yang, Songtao']",Viruses,,,True
d28036629e9cfa447725936de8e8164f37834fe5,PMC,A Chimeric Sudan Virus-Like Particle Vaccine Candidate Produced by a Recombinant Baculovirus System Induces Specific Immune Responses in Mice and Horses,http://dx.doi.org/10.3390/v12010064,PMC7019897,31947873,CC BY,"Ebola virus infections lead to severe hemorrhagic fevers in humans and nonhuman primates; and human fatality rates are as high as 67%–90%. Since the Ebola virus was discovered in 1976, the only available treatments have been medical support or the emergency administration of experimental drugs. The absence of licensed vaccines and drugs against the Ebola virus impedes the prevention of viral infection. In this study, we generated recombinant baculoviruses (rBV) expressing the Sudan virus (SUDV) matrix structural protein (VP40) (rBV-VP40-VP40) or the SUDV glycoprotein (GP) (rBV-GP-GP), and SUDV virus-like particles (VLPs) were produced by co-infection of Sf9 cells with rBV-SUDV-VP40 and rBV-SUDV-GP. The expression of SUDV VP40 and GP in SUDV VLPs was demonstrated by IFA and Western blot analysis. Electron microscopy results demonstrated that SUDV VLPs had a filamentous morphology. The immunogenicity of SUDV VLPs produced in insect cells was evaluated by the immunization of mice. The analysis of antibody responses showed that mice vaccinated with SUDV VLPs and the adjuvant Montanide ISA 201 produced SUDV GP-specific IgG antibodies. Sera from SUDV VLP-immunized mice were able to block infection by SUDV GP pseudotyped HIV, indicating that a neutralizing antibody against the SUDV GP protein was produced. Furthermore, the activation of B cells in the group immunized with VLPs mixed with Montanide ISA 201 was significant one week after the primary immunization. Vaccination with the SUDV VLPs markedly increased the frequency of antigen-specific cells secreting type 1 and type 2 cytokines. To study the therapeutic effects of SUDV antibodies, horses were immunized with SUDV VLPs emulsified in Freund’s complete adjuvant or Freund’s incomplete adjuvant. The results showed that horses could produce SUDV GP-specific antibodies and neutralizing antibodies. These results showed that SUDV VLPs demonstrate excellent immunogenicity and represent a promising approach for vaccine development against SUDV infection. Further, these horse anti-SUDV purified immunoglobulins lay a foundation for SUDV therapeutic drug research.",2020 Jan 3,"['Wu, Fangfang', 'Zhang, Shengnan', 'Zhang, Ying', 'Mo, Ruo', 'Yan, Feihu', 'Wang, Hualei', 'Wong, Gary', 'Chi, Hang', 'Wang, Tiecheng', 'Feng, Na', 'Gao, Yuwei', 'Xia, Xianzhu', 'Zhao, Yongkun', 'Yang, Songtao']",Viruses,,,False
0cfcde84a026bdda19653c843f9da04d2d4ea54f,PMC,The 19th Rocky Mountain Virology Association Meeting,http://dx.doi.org/10.3390/v12010085,PMC7019928,31940824,CC BY,"This autumn, 95 scientists and students from the Rocky Mountain area, along with invited speakers from Colorado, California, Montana, Florida, Louisiana, New York, Maryland, and India, attended the 19th annual meeting of the Rocky Mountain Virology Association that was held at the Colorado State University Mountain Campus located in the Rocky Mountains. The two-day gathering featured 30 talks and 13 posters—all of which focused on specific areas of current virology and prion protein research. The keynote presentation reviewed new tools for microbial discovery and diagnostics. This timely discussion described the opportunities new investigators have to expand the field of microbiology into chronic and acute diseases, the pitfalls of sensitive molecular methods for pathogen discovery, and ways in which microbiology help us understand disruptions in the social fabric that pose pandemic threats at least as real as Ebola or influenza. Other areas of interest included host factors that influence virus replication, in-depth analysis of virus transcription and its effect on host gene expression, and multiple discussions of virus pathology, epidemiology as well as new avenues of diagnosis and treatment. The meeting was held at the peak of fall Aspen colors, surrounded by five mountains >11,000 ft (3.3 km), where the secluded campus provided the ideal setting for extended discussions, outdoor exercise and stargazing. On behalf of the Rocky Mountain Virology Association, this report summarizes 43 selected presentations.",2020 Jan 11,"['Rovnak, Joel', 'St. Clair, Laura A.', 'Lian, Elena', 'McAlister, Carley', 'Perera, Rushika', 'Cohrs, Randall J.']",Viruses,,,False
e63f49d69364214383bb4bd983e941816b11b8da,PMC,Characterization of the Immune Response of MERS-CoV Vaccine Candidates Derived from Two Different Vectors in Mice,http://dx.doi.org/10.3390/v12010125,PMC7019946,31968702,CC BY,"Middle East respiratory syndrome (MERS) is an acute, high-mortality-rate, severe infectious disease caused by an emerging MERS coronavirus (MERS-CoV) that causes severe respiratory diseases. The continuous spread and great pandemic potential of MERS-CoV make it necessarily important to develop effective vaccines. We previously demonstrated that the application of Gram-positive enhancer matrix (GEM) particles as a bacterial vector displaying the MERS-CoV receptor-binding domain (RBD) is a very promising MERS vaccine candidate that is capable of producing potential neutralization antibodies. We have also used the rabies virus (RV) as a viral vector to design a recombinant vaccine by expressing the MERS-CoV S1 (spike) protein on the surface of the RV. In this study, we compared the immunological efficacy of the vaccine candidates in BALB/c mice in terms of the levels of humoral and cellular immune responses. The results show that the rabies virus vector-based vaccine can induce remarkably earlier antibody response and higher levels of cellular immunity than the GEM particles vector. However, the GEM particles vector-based vaccine candidate can induce remarkably higher antibody response, even at a very low dose of 1 µg. These results indicate that vaccines constructed using different vaccine vector platforms for the same pathogen have different rates and trends in humoral and cellular immune responses in the same animal model. This discovery not only provides more alternative vaccine development platforms for MERS-CoV vaccine development, but also provides a theoretical basis for our future selection of vaccine vector platforms for other specific pathogens.",2020 Jan 20,"['Li, Entao', 'Yan, Feihu', 'Huang, Pei', 'Chi, Hang', 'Xu, Shengnan', 'Li, Guohua', 'Liu, Chuanyu', 'Feng, Na', 'Wang, Hualei', 'Zhao, Yongkun', 'Yang, Songtao', 'Xia, Xianzhu']",Viruses,,,True
b788a8861367f5eefe81794e3c77c4a15a872b03,PMC,Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?,http://dx.doi.org/10.3390/v12010014,PMC7020001,31861926,CC BY,"Respiratory viruses infect the human upper respiratory tract, mostly causing mild diseases. However, in vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, causing a more severe disease (e.g., pneumonia). Respiratory viruses can also exacerbate asthma and lead to various types of respiratory distress syndromes. Furthermore, as they can adapt fast and cross the species barrier, some of these pathogens, like influenza A and SARS-CoV, have occasionally caused epidemics or pandemics, and were associated with more serious clinical diseases and even mortality. For a few decades now, data reported in the scientific literature has also demonstrated that several respiratory viruses have neuroinvasive capacities, since they can spread from the respiratory tract to the central nervous system (CNS). Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Like other well-recognized neuroinvasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology). The etiological agent of several neurological disorders remains unidentified. Opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of these disorders whose etiology remains poorly understood. Herein, we present a global portrait of some of the most prevalent or emerging human respiratory viruses that have been associated with possible pathogenic processes in CNS infection, with a special emphasis on human coronaviruses.",2019 Dec 20,"['Desforges, Marc', 'Le Coupanec, Alain', 'Dubeau, Philippe', 'Bourgouin, Andréanne', 'Lajoie, Louise', 'Dubé, Mathieu', 'Talbot, Pierre J.']",Viruses,,,True
98ce22d0a0cab728f1aab48170f1769bb0bc3454,PMC,Population- and Variant-Based Genome Analyses of Viruses from Vaccine-Derived Rabies Cases Demonstrate Product Specific Clusters and Unique Patterns,http://dx.doi.org/10.3390/v12010115,PMC7020022,31963517,CC BY,"Rabies in wildlife has been successfully controlled in parts of Europe and North America using oral rabies vaccination, i.e., the distribution of baits containing live-attenuated virus strains. Occasionally, these vaccines caused vaccine virus-induced rabies cases. To elucidate the mechanisms of genetic selection and the effect of viral populations on these rabies cases, a next generation sequencing approach as well as comprehensive data analyses of the genetic diversity of Street Alabama Dufferin (SAD) and ERA vaccine virus strains and vaccine-induced rabies cases from Canada and several European countries were conducted. As a result, twelve newly generated sets of sequencing data from Canada and Poland were added to a pool of previously investigated samples. While the population-based analysis showed a segregation of viruses of ERA vaccine-induced rabies cases from those of SAD Bern original (SAD Bern(orig))-derived rabies cases, the in-depth variant analysis revealed three distinct combinations of selected variants for the ERA vaccine-induced cases, suggesting the presence of multiple replication-competent haplotypes in the investigated ERA-BHK21 vaccine. Our findings demonstrate the potential of a deep sequencing approach in combination with comprehensive analyses on the consensus, population, and variant level.",2020 Jan 17,"['Calvelage, Sten', 'Smreczak, Marcin', 'Orłowska, Anna', 'Freuling, Conrad Martin', 'Müller, Thomas', 'Fehlner-Gardiner, Christine', 'Nadin-Davis, Susan', 'Höper, Dirk', 'Trębas, Paweł']",Viruses,,,True
549ecd5271e2f5d8e14450001ff82f7c6a0f084d,PMC,Population- and Variant-Based Genome Analyses of Viruses from Vaccine-Derived Rabies Cases Demonstrate Product Specific Clusters and Unique Patterns,http://dx.doi.org/10.3390/v12010115,PMC7020022,31963517,CC BY,"Rabies in wildlife has been successfully controlled in parts of Europe and North America using oral rabies vaccination, i.e., the distribution of baits containing live-attenuated virus strains. Occasionally, these vaccines caused vaccine virus-induced rabies cases. To elucidate the mechanisms of genetic selection and the effect of viral populations on these rabies cases, a next generation sequencing approach as well as comprehensive data analyses of the genetic diversity of Street Alabama Dufferin (SAD) and ERA vaccine virus strains and vaccine-induced rabies cases from Canada and several European countries were conducted. As a result, twelve newly generated sets of sequencing data from Canada and Poland were added to a pool of previously investigated samples. While the population-based analysis showed a segregation of viruses of ERA vaccine-induced rabies cases from those of SAD Bern original (SAD Bern(orig))-derived rabies cases, the in-depth variant analysis revealed three distinct combinations of selected variants for the ERA vaccine-induced cases, suggesting the presence of multiple replication-competent haplotypes in the investigated ERA-BHK21 vaccine. Our findings demonstrate the potential of a deep sequencing approach in combination with comprehensive analyses on the consensus, population, and variant level.",2020 Jan 17,"['Calvelage, Sten', 'Smreczak, Marcin', 'Orłowska, Anna', 'Freuling, Conrad Martin', 'Müller, Thomas', 'Fehlner-Gardiner, Christine', 'Nadin-Davis, Susan', 'Höper, Dirk', 'Trębas, Paweł']",Viruses,,,True
37215fa618869df1820d22f28bace99ea9ceb1fc,PMC,miR-26a Inhibits Feline Herpesvirus 1 Replication by Targeting SOCS5 and Promoting Type I Interferon Signaling,http://dx.doi.org/10.3390/v12010002,PMC7020096,31861450,CC BY,"In response to viral infection, host cells activate various antiviral responses to inhibit virus replication. While feline herpesvirus 1 (FHV-1) manipulates the host early innate immune response in many different ways, the host could activate the antiviral response to counteract it through some unknown mechanisms. MicroRNAs (miRNAs) which serve as a class of regulatory factors in the host, participate in the regulation of the host innate immune response against virus infection. In this study, we found that the expression levels of miR-26a were significantly upregulated upon FHV-1 infection. Furthermore, FHV-1 infection induced the expression of miR-26a via a cGAS-dependent pathway, and knockdown of cellular cGAS significantly blocked the expression of miR-26a induced by poly (dA:dT) or FHV-1 infection. Next, we investigated the biological function of miR-26a during viral infection. miR-26a was able to increase the phosphorylation of STAT1 and promote type I IFN signaling, thus inhibiting viral replication. The mechanism study showed that miR-26a directly targeted host SOCS5. Knockdown of SOCS5 increased the phosphorylation of STAT1 and enhanced the type I IFN-mediated antiviral response, and overexpression of suppressor of the cytokine signalling 5 (SOCS5) decreased the phosphorylation of STAT1 and inhibited the type I IFN-mediated antiviral response. Meanwhile, with the knockdown of SOCS5, the upregulated expression of phosphorylated STAT1 and the anti-virus effect induced by miR-26a were significantly inhibited. Taken together, our data demonstrated a new strategy of host miRNAs against FHV-1 infection by enhancing IFN antiviral signaling.",2019 Dec 18,"['Zhang, Jikai', 'Li, Zhijie', 'Huang, Jiapei', 'Yin, Hang', 'Tian, Jin', 'Qu, Liandong']",Viruses,,,True
bc3dbc06d10839685372f1ac95ce39327854ef48,PMC,miR-26a Inhibits Feline Herpesvirus 1 Replication by Targeting SOCS5 and Promoting Type I Interferon Signaling,http://dx.doi.org/10.3390/v12010002,PMC7020096,31861450,CC BY,"In response to viral infection, host cells activate various antiviral responses to inhibit virus replication. While feline herpesvirus 1 (FHV-1) manipulates the host early innate immune response in many different ways, the host could activate the antiviral response to counteract it through some unknown mechanisms. MicroRNAs (miRNAs) which serve as a class of regulatory factors in the host, participate in the regulation of the host innate immune response against virus infection. In this study, we found that the expression levels of miR-26a were significantly upregulated upon FHV-1 infection. Furthermore, FHV-1 infection induced the expression of miR-26a via a cGAS-dependent pathway, and knockdown of cellular cGAS significantly blocked the expression of miR-26a induced by poly (dA:dT) or FHV-1 infection. Next, we investigated the biological function of miR-26a during viral infection. miR-26a was able to increase the phosphorylation of STAT1 and promote type I IFN signaling, thus inhibiting viral replication. The mechanism study showed that miR-26a directly targeted host SOCS5. Knockdown of SOCS5 increased the phosphorylation of STAT1 and enhanced the type I IFN-mediated antiviral response, and overexpression of suppressor of the cytokine signalling 5 (SOCS5) decreased the phosphorylation of STAT1 and inhibited the type I IFN-mediated antiviral response. Meanwhile, with the knockdown of SOCS5, the upregulated expression of phosphorylated STAT1 and the anti-virus effect induced by miR-26a were significantly inhibited. Taken together, our data demonstrated a new strategy of host miRNAs against FHV-1 infection by enhancing IFN antiviral signaling.",2019 Dec 18,"['Zhang, Jikai', 'Li, Zhijie', 'Huang, Jiapei', 'Yin, Hang', 'Tian, Jin', 'Qu, Liandong']",Viruses,,,False
2089844227bd2ff234044e4b311bf1c2bcb3838c,PMC,Respiratory viruses in mechanically ventilated patients: a pilot study,http://dx.doi.org/10.1186/s12890-020-1082-5,PMC7020345,32054471,CC BY,"BACKGROUND: Respiratory virome is an integral part of the human microbiome and its characterization may contribute to a better understanding of the changes that arise in the disease and, consequently, influence the approach and treatment of patients with acute lower respiratory infections. The aim of this study was to evaluate the presence of respiratory viruses in the lower airways of individuals undergoing invasive mechanical ventilation, with and without acute lower respiratory infection (respectively WRI and WORI groups). METHODS: We studied 44 mini-bronchoalveolar lavage samples (collected with a double catheter, Combicath® kit) from patients with mean age in the seventh decade, 20 from WORI group and 24 from WRI group, who were hospitalized for acute respiratory failure in Intensive Care Units of two hospitals in the Lisbon area. Real-time PCR was applied to verify analyse the presence of 15 common respiratory viruses (adenovirus, human bocavirus, influenza virus A and B, repiratory syncytial virus, human parainfluenza virus types 1, 2, 3 and 4, human enterovirus, human rhinovirus, human metapneumovirus, human coronavirus group 1 (229E, NL63) and 2 (OC43, HKU1). RESULTS: Respiratory viruses were detected in six of the 20 patients in the WORI group: influenza AH3 (n = 2), parainfluenza virus 1/3 (n = 2), human rhinovirus (n = 2), respiratory syncytial virus (n = 1) and human metapneumovirus (n = 1). In the WRI group, respiratory viruses were detected in 12 of the 24 patients: influenza AH3 (n = 3), human rhinovirus (n = 3), respiratory syncytial virus (n = 3), human metapneumovirus (n = 3), human bocavirus (n = 2) and human enterovirus (n = 1). Simultaneous detection of two viruses was recorded in two samples in both groups. CONCLUSIONS: The results of this study suggest the presence of common respiratory viruses in the lower respiratory tract without causing symptomatic infection, even in carefully collected lower samples. This may have important implications on the interpretation of the results on the diagnostic setting.",2020 Feb 13,"['Nazareth, Raquel', 'Chasqueira, Maria-Jesus', 'Rodrigues, Maria-Lúcia', 'Paulino, Carolina', 'Conceição, Catarina', 'Lêdo, Lia', 'Segura, Úrsula', 'Santos, Madalena', 'Messias, António', 'Póvoa, Pedro', 'Paixão, Paulo']",BMC Pulm Med,,,True
f287cdbc6b706443ee5c1a1e50050515d8a613c7,PMC,Detection and characterization of microRNA expression profiling and its target genes in response to canine parvovirus in Crandell Reese Feline Kidney cells,http://dx.doi.org/10.7717/peerj.8522,PMC7023829,32095352,CC BY,"BACKGROUND: MicroRNAs (miRNAs) play an essential role in gene regulators in many biological and molecular phenomena. Unraveling the involvement of miRNA as a key cellular factor during in vitro canine parvovirus (CPV) infection may facilitate the discovery of potential intervention candidates. However, the examination of miRNA expression profiles in CPV in tissue culture systems has not been fully elucidated. METHOD: In the present study, we utilized high-throughput small RNA-seq (sRNA-seq) technology to investigate the altered miRNA profiling in miRNA libraries from uninfected (Control) and CPV-2c infected Crandell Reese Feline Kidney cells. RESULTS: We identified five of known miRNAs (miR-222-5p, miR-365-2-5p, miR-1247-3p, miR-322-5p and miR-361-3p) and three novel miRNAs (Novel 137, Novel 141 and Novel 102) by sRNA-seq with differentially expressed genes in the miRNA repertoire of CPV-infected cells over control. We further predicted the potential target genes of the aforementioned miRNAs using sequence homology algorithms. Notably, the targets of miR-1247-3p exhibited a potential function associated with cellular defense and humoral response to CPV. To extend the probing scheme for gene targets of miR-1247-3p, we explored and performed Gene Ontology (GO) enrichment analysis of its target genes. We discovered 229 putative targets from a total of 38 enriched GO terms. The top over-represented GO enrichment in biological process were lymphocyte activation and differentiation, marginal zone B cell differentiation, negative regulation of cytokine production, negative regulation of programed cell death, and negative regulation of signaling. We next constructed a GO biological process network composed of 28 target genes of miR-1247-3p, of which, some genes, namely BCL6, DLL1, GATA3, IL6, LEF1, LFNG and WNT1 were among the genes with obviously intersected in multiple GO terms. CONCLUSION: The miRNA-1247-3p and its cognate target genes suggested their great potential as novel therapeutic targets or diagnostic biomarkers of CPV or other related viruses.",2020 Feb 12,"['Chuammitri, Phongsakorn', 'Vannamahaxay, Soulasack', 'Sornpet, Benjaporn', 'Pringproa, Kidsadagon', 'Patchanee, Prapas']",PeerJ,,,True
5f28070e492b933fa2cfd460fd67b9f6731c4345,PMC,"Public health event communication under the International Health Regulations (2005) in the Western Pacific Region, September 2006-January 2017",http://dx.doi.org/10.5365/2019.10.1.006,PMC7024699,32110461,CC BY,"• The International Health Regulations, or IHR (2005), establishes timely communication between the World Health Organization (WHO) and Member States to manage acute public health events and protect health security. Experiences of the WHO IHR contact point for the Western Pacific Region demonstrated the communication mechanism has achieved its functions in the Region. • Investment in IHR communication as part of the Asia Pacific Strategy for Emerging Diseases and Public Health Emergencies (APSED III) during peaceful times between public health emergencies builds capacity, confidence and trust in information sharing during emergencies. • IHR communication is integral to the national, regional and global epidemic intelligence and risk assessments system. • Regular simulation exercises (for example, IHR Exercise Crystal) play an important role in testing and strengthening IHR communication. • IHR communication continues to be vital for Member States and WHO country offices to advise on health security.",2019 Sep 27,"['Xi, Li', 'Ailan, Li']",Western Pac Surveill Response J,,,True
b2c1c0ce4885d8a926e9ff2b97aeb3ea220286b0,PMC,Novel Insights Into Immune Systems of Bats,http://dx.doi.org/10.3389/fimmu.2020.00026,PMC7025585,32117225,CC BY,"In recent years, viruses similar to those that cause serious disease in humans and other mammals have been detected in apparently healthy bats. These include filoviruses, paramyxoviruses, and coronaviruses that cause severe diseases such as Ebola virus disease, Marburg haemorrhagic fever and severe acute respiratory syndrome (SARS) in humans. The evolution of flight in bats seem to have selected for a unique set of antiviral immune responses that control virus propagation, while limiting self-damaging inflammatory responses. Here, we summarize our current understanding of antiviral immune responses in bats and discuss their ability to co-exist with emerging viruses that cause serious disease in other mammals. We highlight how this knowledge may help us to predict viral spillovers into new hosts and discuss future directions for the field.",2020 Jan 24,"['Banerjee, Arinjay', 'Baker, Michelle L.', 'Kulcsar, Kirsten', 'Misra, Vikram', 'Plowright, Raina', 'Mossman, Karen']",Front Immunol,,,True
78d5d3279bea15af4aaa52fe9b3302d52f657dc9,PMC,Antiviral Drugs Against Severe Fever With Thrombocytopenia Syndrome Virus Infection,http://dx.doi.org/10.3389/fmicb.2020.00150,PMC7026129,32117168,CC BY,"Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by SFTS virus (SFTSV), which is a novel bunyavirus. SFTSV was first isolated from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction in China. Subsequently, it was found to be widely distributed in Southeast Asia (Korea, Japan, and Vietnam). SFTSV can be transmitted not only from ticks but also from domestic animals, companion animals, and humans. Because the case fatality rate of SFTS is high (6–30%), development of specific and effective treatment for SFTS is required. Studies of potential antiviral drugs for SFTS-specific therapy have been conducted on existing or newly discovered agents in vitro and in vivo, with ribavirin and favipiravir being the most promising candidates. While animal experiments and retrospective studies have demonstrated the limited efficacy of ribavirin, it was also speculated that ribavirin would be effective in patients with a viral load <1 × 10(6) copies/mL. Favipiravir showed higher efficacy than ribavirin against SFTSV in in vitro assays and greater efficacy in animal models, even administrated 3 days after the virus inoculation. Although clinical trials evaluating the efficacy of favipiravir in SFTS patients in Japan are underway, this has yet to be confirmed. Other drugs, including hexachlorophene, calcium channel blockers, 2′-fluoro-2′-deoxycytidine, caffeic acid, amodiaquine, and interferons, have also been evaluated for their inhibitory efficacy against SFTSV. Among them, calcium channel blockers are promising because in addition to their efficacy in vitro and in vivo, retrospective clinical data have indicated that nifedipine, one of the calcium channel blockers, reduced the case fatality rate by >5-fold. Although further research is necessary to develop SFTS-specific therapy, considerable progress has been achieved in this area. Here we summarize and discuss recent advances in antiviral drugs against SFTSV.",2020 Feb 11,"['Takayama-Ito, Mutsuyo', 'Saijo, Masayuki']",Front Microbiol,,,True
bbc8c0fb749a7bac1030cf1301654f7063c612dd,PMC,A nucleobase-binding pocket in a viral RNA-dependent RNA polymerase contributes to elongation complex stability,http://dx.doi.org/10.1093/nar/gkz1170,PMC7026628,31863580,CC BY,"The enterovirus 71 (EV71) 3D(pol) is an RNA-dependent RNA polymerase (RdRP) that plays the central role in the viral genome replication, and is an important target in antiviral studies. Here, we report a crystal structure of EV71 3D(pol) elongation complex (EC) at 1.8 Å resolution. The structure reveals that the 5′-end guanosine of the downstream RNA template interacts with a fingers domain pocket, with the base sandwiched by H44 and R277 side chains through hydrophobic stacking interactions, and these interactions are still maintained after one in-crystal translocation event induced by nucleotide incorporation, implying that the pocket could regulate the functional properties of the polymerase by interacting with RNA. When mutated, residue R277 showed an impact on virus proliferation in virological studies with residue H44 having a synergistic effect. In vitro biochemical data further suggest that mutations at these two sites affect RNA binding, EC stability, but not polymerase catalytic rate (k(cat)) and apparent NTP affinity (K(M,NTP)). We propose that, although rarely captured by crystallography, similar surface pocket interaction with nucleobase may commonly exist in nucleic acid motor enzymes to facilitate their processivity. Potential applications in antiviral drug and vaccine development are also discussed.",2020 Feb 20,"['Shi, Wei', 'Ye, Han-Qing', 'Deng, Cheng-Lin', 'Li, Rui', 'Zhang, Bo', 'Gong, Peng']",Nucleic Acids Res,,,True
331efc82eb143a10c93bb64327998b525bc461a6,PMC,Characterization of Lactic Acid Bacteria Isolated From the Gastrointestinal Tract of a Wild Boar as Potential Probiotics,http://dx.doi.org/10.3389/fvets.2020.00049,PMC7026679,32118070,CC BY,"Lactic acid bacteria (LAB) are major microorganisms used for probiotic purposes and prime parts of the human and mammalian gut microbiota, which exert important health-promoting effects on the host. The present study aimed to evaluate and compare the probiotic potential and safety of LAB strains isolated from the gastrointestinal tract of a wild boar from the Greater Khingan Mountains, China. Amongst all of the isolated LAB strains, five isolates identified as Lactobacillus mucosae, Lactobacillus salivarius, Enterococcus hirae, Enterococcus durans, and Enterococcus faecium, were remarkably resistant to acid and bile salt. The probiotic characteristics (including adhesion capability, antimicrobial activities, autoaggregation, and coaggregation abilities), and safety properties (including hemolytic activity, antibiotic resistance, absence/presence of virulence factors, and in vivo safety) were evaluated. The results showed that all five isolates exhibited high adhesive potential, remarkable aggregation capacity, and antibacterial activities. Upon assessment of the safety, these strains were negative for hemolytic activity and all tested virulence genes. In vivo safety assessment showed no adverse effects of isolated strains supplementation on the body weight gain and organ indices of the treated mice. This study revealed that these LAB isolates, especially L. salivarius M2-71, possess desirable probiotic properties and have great potentials for the development of feed additives for animals to promote health.",2020 Feb 11,"['Li, Miao', 'Wang, Yi', 'Cui, Hongyu', 'Li, Yongfeng', 'Sun, Yuan', 'Qiu, Hua-Ji']",Front Vet Sci,,,True
5d254ed178c092d3639ce70ae9653593acc471f9,PMC,SARS to novel coronavirus – old lessons and new lessons,http://dx.doi.org/10.1017/S0950268820000254,PMC7026896,32019614,CC BY,"The response to the novel coronavirus outbreak in China suggests that many of the lessons from the 2003 SARS epidemic have been implemented and the response improved as a consequence. Nevertheless some questions remain and not all lessons have been successful. The national and international response demonstrates the complex link between public health, science and politics when an outbreak threatens to impact on global economies and reputations. The unprecedented measures implemented in China are a bold attempt to control the outbreak – we need to understand their effectiveness to balance costs and benefits for similar events in the future.",,"['McCloskey, Brian', 'Heymann, David L.']",Epidemiol Infect.; 148:e22,,,True
9816051343f6acf13246fd5957e876a4db2c1ab7,PMC,Resource allocation for biomedical research: analysis of investments by major funders,http://dx.doi.org/10.1186/s12961-020-0532-0,PMC7027210,32066463,CC BY,"BACKGROUND: Data on grants for biomedical research by 10 major funders of health research were collected from the World RePORT platform to explore what is being funded, by whom and where. This analysis is part of the World Health Organization Global Observatory on Health Research and Development’s work with the overall aim to enable evidence-informed deliberations and decisions on new investments in health research and development. The analysis expands on the interactive data visualisations of these data on the Observatory’s website and describes the methods used to enable the categorisation of grants by health categories using automated data-mining techniques. METHODS: Grants data were extracted from the World RePORT platform for 2016, the most recent year with data from all funders. A data-mining algorithm was developed in Java to categorise grants by health category. The analysis explored the distribution of grants by funder, recipient country and organisation, type of grant, health category, average grant duration, and the nature of collaborations between recipients of direct grants and the institutions they collaborated with. RESULTS: Out of a total of 69,420 grants in 2016, the United States of America’s National Institutes of Health funded the greatest number of grants (52,928; 76%) and had the longest average grant duration (6 years and 10 months). Grants for research constituted 70.4% (48,879) of all types of grants, followed by grants for training (13,008; 18.7%) and meetings (2907; 4.2%). Of grant recipients by income group, low-income countries received only 0.2% (165) of all grants. Almost three-quarters of all grants were for non-communicable diseases (72%; 40,035), followed by communicable, maternal, perinatal and nutritional conditions (20%; 11,123), and injuries (6%; 3056). Only 1.1% of grants were for neglected tropical diseases and 0.4% for priority diseases on the WHO list of highly infectious (R&D blueprint) pathogens. CONCLUSIONS: The findings highlight the importance of considering funding decisions by other actors in future health research and capacity-strengthening decisions. This will not only improve efficiency and equity in allocating scarce resources but will also allow informed investment decisions that aim to support research on public health needs and neglected areas.",2020 Feb 17,"['Ralaidovy, Ambinintsoa H.', 'Adam, Taghreed', 'Boucher, Philippe']",Health Res Policy Syst,,,True
b4e276ce333eefee623e9d425f5c538c64b567cc,PMC,The expanding role of mass spectrometry in the field of vaccine development,http://dx.doi.org/10.1002/mas.21571,PMC7027533,29852530,CC BY,"Biological mass spectrometry has evolved as a core analytical technology in the last decade mainly because of its unparalleled ability to perform qualitative as well as quantitative profiling of enormously complex biological samples with high mass accuracy, sensitivity, selectivity and specificity. Mass spectrometry‐based techniques are also routinely used to assess glycosylation and other post‐translational modifications, disulfide bond linkage, and scrambling as well as for the detection of host cell protein contaminants in the field of biopharmaceuticals. The role of mass spectrometry in vaccine development has been very limited but is now expanding as the landscape of global vaccine development is shifting towards the development of recombinant vaccines. In this review, the role of mass spectrometry in vaccine development is presented, some of the ongoing efforts to develop vaccines for diseases with global unmet medical need are discussed and the regulatory challenges of implementing mass spectrometry techniques in a quality control laboratory setting are highlighted.",2020 May 31 Mar-Apr,"['Sharma, Vaneet Kumar', 'Sharma, Ity', 'Glick, James']",Mass Spectrom Rev,,,True
fb8e2e76092de55f4b7f22bd0106f6c3853ca3bd,PMC,Development and characterization of a continuous cell line (EL) from the liver of European eel Anguilla anguilla,http://dx.doi.org/10.1002/cbin.11276,PMC7028054,31814207,CC BY,"In the present study, a new hepatic tissue‐origin cell line from European eel Anguilla anguilla has been developed and characterized. This cell line designated EL has been maintained in Leibovitz L‐15 supplemented with 10% fetal bovine serum over 72 months, and subcultured more than 90 times. The EL cell line consisted predominantly of fibroblast‐like cells, which could survive over 100 days in vitro, and could grow at 15–32°C. The optimum temperature for growth was 27°C. The chromosome analysis revealed a modal diploid karyotype of 2n = 38. The origin of this cell line was confirmed by the 18S recombinant (r)RNA sequencing. The susceptibility test indicated significant cytopathic effects in the EL cells with regard to the Rana grylio virus and the Herpesvirus anguillae. The viral replication was confirmed by transmission electron microscopy and polymerase chain reaction analysis. Following poly (I:C) exposure, the expression levels of the immune‐related molecules interferon regulatory factor‐7 (irf7) and transforming growth factor‐β (TGF‐β) were downregulated in EL cells, whereas the expression levels of the rf3 and the cytochrome P450 (CYP450) were upregulated. All four genes were significantly upregulated following inflammation by lipopolysaccharide (LPS). These data suggested the application of EL cell line for viral identification, as well as for immunodiagnosis and pharmacological targeting.",2020 Mar 19,"['Zheng, Zaiyu', 'Yang, Jinxian', 'Ge, Junqing', 'Chi, Hongshu', 'Chen, Bin', 'Fang, Qinmei', 'Gong, Hui']",Cell Biol Int,,,True
6a8270cbdb7222a8a18248627314bdd6c9823cd4,PMC,Silicone pneumonitis after gluteal filler: a case report and literature review,http://dx.doi.org/10.1002/rcr2.538,PMC7028525,32076554,CC BY,"Liquid silicone (polydimethylsiloxane) is an inert material that is commonly used for cosmetic purpose. Silicone embolization syndrome (SES) can rapidly progress to pneumonitis as a consequence of the injection of nonmedical‐grade liquid silicone. We describe a case of severe silicone pneumonitis complicated with acute respiratory distress syndrome and bilateral pneumothorax secondary to silicone gluteal augmentation. In this case report, we aim to discuss our experience and approach in managing an uncommon case of SES.",2020 Feb 18,"['Ng, Boon Hau', 'Mat, Wan Rahiza Wan', 'Abeed, Nik Nuratiqah Nik', 'Hamid, Mohamed Faisal Abdul', 'Yu‐Lin, Andrea Ban', 'Soo, Chun Ian']",Respirol Case Rep,,,True
059d5acb8af8bd2bedab06b5dcc0510691fe0f1e,PMC,"Laboratory readiness and response for novel coronavirus (2019-nCoV) in expert laboratories in 30 EU/EEA countries, January 2020",http://dx.doi.org/10.2807/1560-7917.ES.2020.25.6.2000082,PMC7029448,32046815,CC BY,"Timely detection of novel coronavirus (2019-nCoV) infection cases is crucial to interrupt the spread of this virus. We assessed the required expertise and capacity for molecular detection of 2019-nCoV in specialised laboratories in 30 European Union/European Economic Area (EU/EEA) countries. Thirty-eight laboratories in 24 EU/EEA countries had diagnostic tests available by 29 January 2020. A coverage of all EU/EEA countries was expected by mid-February. Availability of primers/probes, positive controls and personnel were main implementation barriers.",2020 Feb 13,"['Reusken, Chantal B.E.M.', 'Broberg, Eeva K.', 'Haagmans, Bart', 'Meijer, Adam', 'Corman, Victor M.', 'Papa, Anna', 'Charrel, Remi', 'Drosten, Christian', 'Koopmans, Marion', 'Leitmeyer, Katrin', None]",Euro Surveill,,,True
90de2d957e1960b948b8c38c9877f9eca983f9eb,PMC,Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak,http://dx.doi.org/10.2807/1560-7917.ES.2020.25.6.2000110,PMC7029449,32046814,CC BY,,2020 Feb 13,"['Cowling, Benjamin J', 'Leung, Gabriel M']",Euro Surveill,,,True
c2986721c337e4c827cf3d11c3c9a40bcff4d530,PMC,"First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020",http://dx.doi.org/10.2807/1560-7917.ES.2020.25.6.2000094,PMC7029452,32070465,CC BY,"A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) causing a cluster of respiratory infections (coronavirus disease 2019, COVID-19) in Wuhan, China, was identified on 7 January 2020. The epidemic quickly disseminated from Wuhan and as at 12 February 2020, 45,179 cases have been confirmed in 25 countries, including 1,116 deaths. Strengthened surveillance was implemented in France on 10 January 2020 in order to identify imported cases early and prevent secondary transmission. Three categories of risk exposure and follow-up procedure were defined for contacts. Three cases of COVID-19 were confirmed on 24 January, the first cases in Europe. Contact tracing was immediately initiated. Five contacts were evaluated as at low risk of exposure and 18 at moderate/high risk. As at 12 February 2020, two cases have been discharged and the third one remains symptomatic with a persistent cough, and no secondary transmission has been identified. Effective collaboration between all parties involved in the surveillance and response to emerging threats is required to detect imported cases early and to implement adequate control measures.",2020 Feb 13,"['Bernard Stoecklin, Sibylle', 'Rolland, Patrick', 'Silue, Yassoungo', 'Mailles, Alexandra', 'Campese, Christine', 'Simondon, Anne', 'Mechain, Matthieu', 'Meurice, Laure', 'Nguyen, Mathieu', 'Bassi, Clément', 'Yamani, Estelle', 'Behillil, Sylvie', 'Ismael, Sophie', 'Nguyen, Duc', 'Malvy, Denis', 'Lescure, François Xavier', 'Georges, Scarlett', 'Lazarus, Clément', 'Tabaï, Anouk', 'Stempfelet, Morgane', 'Enouf, Vincent', 'Coignard, Bruno', 'Levy-Bruhl, Daniel', None]",Euro Surveill,,,False
37e17a2bab698f8850dc89f7689eda93502821fb,PMC,"First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020",http://dx.doi.org/10.2807/1560-7917.ES.2020.25.6.2000094,PMC7029452,32070465,CC BY,"A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) causing a cluster of respiratory infections (coronavirus disease 2019, COVID-19) in Wuhan, China, was identified on 7 January 2020. The epidemic quickly disseminated from Wuhan and as at 12 February 2020, 45,179 cases have been confirmed in 25 countries, including 1,116 deaths. Strengthened surveillance was implemented in France on 10 January 2020 in order to identify imported cases early and prevent secondary transmission. Three categories of risk exposure and follow-up procedure were defined for contacts. Three cases of COVID-19 were confirmed on 24 January, the first cases in Europe. Contact tracing was immediately initiated. Five contacts were evaluated as at low risk of exposure and 18 at moderate/high risk. As at 12 February 2020, two cases have been discharged and the third one remains symptomatic with a persistent cough, and no secondary transmission has been identified. Effective collaboration between all parties involved in the surveillance and response to emerging threats is required to detect imported cases early and to implement adequate control measures.",2020 Feb 13,"['Bernard Stoecklin, Sibylle', 'Rolland, Patrick', 'Silue, Yassoungo', 'Mailles, Alexandra', 'Campese, Christine', 'Simondon, Anne', 'Mechain, Matthieu', 'Meurice, Laure', 'Nguyen, Mathieu', 'Bassi, Clément', 'Yamani, Estelle', 'Behillil, Sylvie', 'Ismael, Sophie', 'Nguyen, Duc', 'Malvy, Denis', 'Lescure, François Xavier', 'Georges, Scarlett', 'Lazarus, Clément', 'Tabaï, Anouk', 'Stempfelet, Morgane', 'Enouf, Vincent', 'Coignard, Bruno', 'Levy-Bruhl, Daniel', None]",Euro Surveill,,,True
6a93283b499ae5bc6aaf29f14e701dc8f25138ea,PMC,"Critical care response to a hospital outbreak of the 2019-nCoV infection in Shenzhen, China",http://dx.doi.org/10.1186/s13054-020-2786-x,PMC7029610,32070391,CC BY,,2020 Feb 19,"['Liu, Yong', 'Li, Jinxiu', 'Feng, Yongwen']",Crit Care,,,True
da2e71598a773b197d08b2521a8fb1a2818bdd10,PMC,Villains or heroes? The raison d'être of viruses,http://dx.doi.org/10.1002/cti2.1114,PMC7029637,32099651,CC BY,"The relationship between humans and viruses has a long history. Since the first identification of viruses in the 19th century, we have considered them to be ‘pathogens’ and have studied their mechanisms of replication and pathogenicity to combat the diseases that they cause. However, the relationships between hosts and viruses are various and virus infections do not necessarily cause diseases in their hosts. Rather, recent studies have shown that viral infections sometimes have beneficial effects on the biological functions and/or evolution of hosts. Here, we provide some insight into the positive side of viruses.",2020 Feb 19,"['Watanabe, Tokiko', 'Kawaoka, Yoshihiro']",Clin Transl Immunology,,,True
5a17ed3e4abf295f5820c65f56398266c1baae98,PMC,"Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China",http://dx.doi.org/10.12688/f1000research.22211.2,PMC7029759,32117569,CC BY,"A novel coronavirus (2019-nCoV) originating in Wuhan, China presents a potential respiratory viral pandemic to the world population. Current efforts are focused on containment and quarantine of infected individuals. Ultimately, the outbreak could be controlled with a protective vaccine to prevent 2019-nCoV infection. While vaccine research should be pursued intensely, there exists today no therapy to treat 2019-nCoV upon infection, despite an urgent need to find options to help these patients and preclude potential death. Herein, I review the potential options to treat 2019-nCoV in patients, with an emphasis on the necessity for speed and timeliness in developing new and effective therapies in this outbreak. I consider the options of drug repurposing, developing neutralizing monoclonal antibody therapy, and an oligonucleotide strategy targeting the viral RNA genome, emphasizing the promise and pitfalls of these approaches. Finally, I advocate for the fastest strategy to develop a treatment now, which could be resistant to any mutations the virus may have in the future. The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain (ACE2-Fc), providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. The ACE2-Fc therapy would also supplement decreased ACE2 levels in the lungs during infection, thereby directly treating acute respiratory distress pathophysiology as a third mechanism of action. The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drug today to treat patients under compassionate use, while formal clinical trials are later undertaken. Such a treatment could help infected patients before a protective vaccine is developed and widely available in the coming months to year(s).",2020 Feb 7,"Kruse, Robert L.",F1000Res,,,True
facbfdfa7189ca9ff83dc30e5d241ab22e962dbf,PMC,Frontiers in antiviral therapy and immunotherapy,http://dx.doi.org/10.1002/cti2.1115,PMC7030942,32099652,CC BY,,2020 Feb 19,"Heaton, Steven M",Clin Transl Immunology,,,True
9e8410e170ac72b3ccb909c2807403fc777fdf4c,PMC,Integration of shared-pathogen networks and machine learning reveals the key aspects of zoonoses and predicts mammalian reservoirs,http://dx.doi.org/10.1098/rspb.2019.2882,PMC7031665,32019444,CC BY,"Diseases that spread to humans from animals, zoonoses, pose major threats to human health. Identifying animal reservoirs of zoonoses and predicting future outbreaks are increasingly important to human health and well-being and economic stability, particularly where research and resources are limited. Here, we integrate complex networks and machine learning approaches to develop a new approach to identifying reservoirs. An exhaustive dataset of mammal–pathogen interactions was transformed into networks where hosts are linked via their shared pathogens. We present a methodology for identifying important and influential hosts in these networks. Ensemble models linking network characteristics with phylogeny and life-history traits are then employed to predict those key hosts and quantify the roles they undertake in pathogen transmission. Our models reveal drivers explaining host importance and demonstrate how these drivers vary by pathogen taxa. Host importance is further integrated into ensemble models to predict reservoirs of zoonoses of various pathogen taxa and quantify the extent of pathogen sharing between humans and mammals. We establish predictors of reservoirs of zoonoses, showcasing host influence to be a key factor in determining these reservoirs. Finally, we provide new insight into the determinants of zoonosis-sharing, and contrast these determinants across major pathogen taxa.",2020 Feb 12,"['Wardeh, Maya', 'Sharkey, Kieran J.', 'Baylis, Matthew']",Proc Biol Sci,,,True
7fa5d8f8aad3bd29445e80797c469668a681591a,PMC,Integration of shared-pathogen networks and machine learning reveals the key aspects of zoonoses and predicts mammalian reservoirs,http://dx.doi.org/10.1098/rspb.2019.2882,PMC7031665,32019444,CC BY,"Diseases that spread to humans from animals, zoonoses, pose major threats to human health. Identifying animal reservoirs of zoonoses and predicting future outbreaks are increasingly important to human health and well-being and economic stability, particularly where research and resources are limited. Here, we integrate complex networks and machine learning approaches to develop a new approach to identifying reservoirs. An exhaustive dataset of mammal–pathogen interactions was transformed into networks where hosts are linked via their shared pathogens. We present a methodology for identifying important and influential hosts in these networks. Ensemble models linking network characteristics with phylogeny and life-history traits are then employed to predict those key hosts and quantify the roles they undertake in pathogen transmission. Our models reveal drivers explaining host importance and demonstrate how these drivers vary by pathogen taxa. Host importance is further integrated into ensemble models to predict reservoirs of zoonoses of various pathogen taxa and quantify the extent of pathogen sharing between humans and mammals. We establish predictors of reservoirs of zoonoses, showcasing host influence to be a key factor in determining these reservoirs. Finally, we provide new insight into the determinants of zoonosis-sharing, and contrast these determinants across major pathogen taxa.",2020 Feb 12,"['Wardeh, Maya', 'Sharkey, Kieran J.', 'Baylis, Matthew']",Proc Biol Sci,,,False
30b4f6254119ea425c5370fe40f3def0500fa359,PMC,Integration of shared-pathogen networks and machine learning reveals the key aspects of zoonoses and predicts mammalian reservoirs,http://dx.doi.org/10.1098/rspb.2019.2882,PMC7031665,32019444,CC BY,"Diseases that spread to humans from animals, zoonoses, pose major threats to human health. Identifying animal reservoirs of zoonoses and predicting future outbreaks are increasingly important to human health and well-being and economic stability, particularly where research and resources are limited. Here, we integrate complex networks and machine learning approaches to develop a new approach to identifying reservoirs. An exhaustive dataset of mammal–pathogen interactions was transformed into networks where hosts are linked via their shared pathogens. We present a methodology for identifying important and influential hosts in these networks. Ensemble models linking network characteristics with phylogeny and life-history traits are then employed to predict those key hosts and quantify the roles they undertake in pathogen transmission. Our models reveal drivers explaining host importance and demonstrate how these drivers vary by pathogen taxa. Host importance is further integrated into ensemble models to predict reservoirs of zoonoses of various pathogen taxa and quantify the extent of pathogen sharing between humans and mammals. We establish predictors of reservoirs of zoonoses, showcasing host influence to be a key factor in determining these reservoirs. Finally, we provide new insight into the determinants of zoonosis-sharing, and contrast these determinants across major pathogen taxa.",2020 Feb 12,"['Wardeh, Maya', 'Sharkey, Kieran J.', 'Baylis, Matthew']",Proc Biol Sci,,,True
9bfc043d8a0d90892e9183f75dbe141a30fd68b8,PMC,Comparison of the performance of ITS1 and ITS2 as barcodes in amplicon-based sequencing of bioaerosols,http://dx.doi.org/10.7717/peerj.8523,PMC7032056,32110484,CC BY,"This paper presents the performance of two eukaryotic genomic ribosomal regions, ITS1 and ITS2, in describing fungal diversity in aerosol samples using amplicon-based High-Throughput Sequencing (HTS). Composting sites, biomethanization facilities, and dairy farms, all affected by the presence of fungi, were visited to collect air samples. The amplicon-based HTS approach is a target enrichment method that relies on the amplification of a specific target using particular primers before sequencing. Thus, the results are highly dependent on the quality of amplification. For this reason, the authors of this paper used a shotgun metagenomic approach to compare its outcome with the amplicon-based method. Indeed, shotgun metagenomic does not rely on any amplification prior to sequencing, because all genes are sequenced without a specific target. In addition, culture methods were added to the analyses in biomethanization and dairy farms samples to validate their contribution to fungal diversity of aerosols. The results obtained are unequivocal towards ITS1 outperformance to ITS2 in terms of richness, and taxonomic coverage. The differential abundance analysis did demonstrate that some taxa were exclusively detected only by ITS2, and vice-versa for ITS1. However, the shotgun metagenomic approach showed a taxonomic profile more resembling to ITS1 than ITS2. Based on these results, neither of the barcodes evaluated is perfect in terms of distinguishing all species. Using both barcodes offers a broader view of the fungal aerosol population. However, with the actual knowledge, the authors strongly recommend using ITS1 as a universal fungal barcode for quick general analyses of diversity and when limited financial resources are available, primarily due its ability to capture taxonomic profiles similar to those obtained using the shotgun metagenomic. The culture comparison with amplicon-based sequencing showed the complementarity of both approaches in describing the most abundant taxa.",2020 Feb 17,"['Mbareche, Hamza', 'Veillette, Marc', 'Bilodeau, Guillaume', 'Duchaine, Caroline']",PeerJ,,,True
825b7017130bb5fd2064e841c25f5d01e4da11c5,PMC,Comparison of the performance of ITS1 and ITS2 as barcodes in amplicon-based sequencing of bioaerosols,http://dx.doi.org/10.7717/peerj.8523,PMC7032056,32110484,CC BY,"This paper presents the performance of two eukaryotic genomic ribosomal regions, ITS1 and ITS2, in describing fungal diversity in aerosol samples using amplicon-based High-Throughput Sequencing (HTS). Composting sites, biomethanization facilities, and dairy farms, all affected by the presence of fungi, were visited to collect air samples. The amplicon-based HTS approach is a target enrichment method that relies on the amplification of a specific target using particular primers before sequencing. Thus, the results are highly dependent on the quality of amplification. For this reason, the authors of this paper used a shotgun metagenomic approach to compare its outcome with the amplicon-based method. Indeed, shotgun metagenomic does not rely on any amplification prior to sequencing, because all genes are sequenced without a specific target. In addition, culture methods were added to the analyses in biomethanization and dairy farms samples to validate their contribution to fungal diversity of aerosols. The results obtained are unequivocal towards ITS1 outperformance to ITS2 in terms of richness, and taxonomic coverage. The differential abundance analysis did demonstrate that some taxa were exclusively detected only by ITS2, and vice-versa for ITS1. However, the shotgun metagenomic approach showed a taxonomic profile more resembling to ITS1 than ITS2. Based on these results, neither of the barcodes evaluated is perfect in terms of distinguishing all species. Using both barcodes offers a broader view of the fungal aerosol population. However, with the actual knowledge, the authors strongly recommend using ITS1 as a universal fungal barcode for quick general analyses of diversity and when limited financial resources are available, primarily due its ability to capture taxonomic profiles similar to those obtained using the shotgun metagenomic. The culture comparison with amplicon-based sequencing showed the complementarity of both approaches in describing the most abundant taxa.",2020 Feb 17,"['Mbareche, Hamza', 'Veillette, Marc', 'Bilodeau, Guillaume', 'Duchaine, Caroline']",PeerJ,,,False
6413beddc3f8af0a526e84316ae46e44dab8ee7e,PMC,Fungal diseases as neglected pathogens: A wake-up call to public health officials,http://dx.doi.org/10.1371/journal.pntd.0007964,PMC7032689,32078635,CC BY,,2020 Feb 20,"['Rodrigues, Marcio L.', 'Nosanchuk, Joshua D.']",PLoS Negl Trop Dis,,,True
acdc7132a3cc967450623c8ddcb38ec4214f6850,PMC,Secular trends in incidence of type 1 and type 2 diabetes in Hong Kong: A retrospective cohort study,http://dx.doi.org/10.1371/journal.pmed.1003052,PMC7032690,32078650,CC BY,"BACKGROUND: There is very limited data on the time trend of diabetes incidence in Asia. Using population-level data, we report the secular trend of the incidence of type 1 and type 2 diabetes in Hong Kong between 2002 and 2015. METHODS AND FINDINGS: The Hong Kong Diabetes Surveillance Database hosts clinical information on people with diabetes receiving care under the Hong Kong Hospital Authority, a statutory body that governs all public hospitals and clinics. Sex-specific incidence rates were standardised to the age structure of the World Health Organization population. Joinpoint regression analysis was used to describe incidence trends. A total of 562,022 cases of incident diabetes (type 1 diabetes [n = 2,426]: mean age at diagnosis is 32.5 years, 48.4% men; type 2 diabetes [n = 559,596]: mean age at diagnosis is 61.8 years, 51.9% men) were included. Among people aged <20 years, incidence of both type 1 and type 2 diabetes increased. For type 1 diabetes, the incidence increased from 3.5 (95% CI 2.2–4.9) to 5.3 (95% CI 3.4–7.1) per 100,000 person-years (average annual percentage change [AAPC] 3.6% [95% CI 0.2–7.1], p < 0.05) in boys and from 4.3 (95% CI 2.7–5.8) to 6.4 (95% CI 4.3–8.4) per 100,000 person-years (AAPC 4.7% [95% CI 1.7–7.7], p < 0.05] in girls; for type 2 diabetes, the incidence increased from 4.6 (95% CI 3.2–6.0) to 7.5 (95% CI 5.5–9.6) per 100,000 person-years (AAPC 5.9% [95% CI 3.4–8.5], p < 0.05) in boys and from 5.9 (95% CI 4.3–7.6) to 8.5 (95% CI 6.2–10.8) per 100,000 person-years (AAPC 4.8% [95% CI 2.7–7.0], p < 0.05) in girls. In people aged 20 to <40 years, incidence of type 1 diabetes remained stable, but incidence of type 2 diabetes increased over time from 75.4 (95% CI 70.1–80.7) to 110.8 (95% CI 104.1–117.5) per 100,000 person-years (AAPC 4.2% [95% CI 3.1–5.3], p < 0.05) in men and from 45.0 (95% CI 41.4–48.6) to 62.1 (95% CI 57.8–66.3) per 100,000 person-years (AAPC 3.3% [95% CI 2.3–4.2], p < 0.05) in women. In people aged 40 to <60 years, incidence of type 2 diabetes increased until 2011/2012 and then flattened. In people aged ≥60 years, incidence was stable in men and declined in women after 2011. No trend was identified in the incidence of type 1 diabetes in people aged ≥20 years. The present study is limited by its reliance on electronic medical records for identification of people with diabetes, which may result in incomplete capture of diabetes cases. The differentiation of type 1 and type 2 diabetes was based on an algorithm subject to potential misclassification. CONCLUSIONS: There was an increase in incidence of type 2 diabetes in people aged <40 years and stabilisation in people aged ≥40 years. Incidence of type 1 diabetes continued to climb in people aged <20 years but remained constant in other age groups.",2020 Feb 20,"['Luk, Andrea O. Y.', 'Ke, Calvin', 'Lau, Eric S. H.', 'Wu, Hongjiang', 'Goggins, William', 'Ma, Ronald C. W.', 'Chow, Elaine', 'Kong, Alice P. S.', 'So, Wing-Yee', 'Chan, Juliana C. N.']",PLoS Med,,,True
fbaf6a3ac63158b74ca6b50f01c98d56936a844d,PMC,RNA decay during gammaherpesvirus infection reduces RNA polymerase II occupancy of host promoters but spares viral promoters,http://dx.doi.org/10.1371/journal.ppat.1008269,PMC7032723,32032393,CC BY,"In mammalian cells, widespread acceleration of cytoplasmic mRNA degradation is linked to impaired RNA polymerase II (Pol II) transcription. This mRNA decay-induced transcriptional repression occurs during infection with gammaherpesviruses including Kaposi’s sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV68), which encode an mRNA endonuclease that initiates widespread RNA decay. Here, we show that MHV68-induced mRNA decay leads to a genome-wide reduction of Pol II occupancy at mammalian promoters. This reduced Pol II occupancy is accompanied by down-regulation of multiple Pol II subunits and TFIIB in the nucleus of infected cells, as revealed by mass spectrometry-based global measurements of protein abundance. Viral genes, despite the fact that they require Pol II for transcription, escape transcriptional repression. Protection is not governed by viral promoter sequences; instead, location on the viral genome is both necessary and sufficient to escape the transcriptional repression effects of mRNA decay. We propose a model in which the ability to escape from transcriptional repression is linked to the localization of viral DNA within replication compartments, providing a means for these viruses to counteract decay-induced transcript loss.",2020 Feb 7,"['Hartenian, Ella', 'Gilbertson, Sarah', 'Federspiel, Joel D.', 'Cristea, Ileana M.', 'Glaunsinger, Britt A.']",PLoS Pathog,,,True
21d29c71a5678eaee998b3f23e32887c9d82b7dd,PMC,Inhibition of Porphyromonas gulae and periodontal disease in dogs by a combination of clindamycin and interferon alpha,http://dx.doi.org/10.1038/s41598-020-59730-9,PMC7033253,32080231,CC BY,"Porphyromonas gulae is a major periodontal pathogen in dogs, which can be transmitted to their owners. A major virulence factor of P. gulae consists of a 41-kDa filamentous appendage (FimA) on the cell surface, which is classified into three genotypes: A, B, and C. Thus far, inhibition of periodontal disease in dogs remains difficult. The present study assessed the inhibitory effects of a combination of clindamycin and interferon alpha (IFN-α) formulation against P. gulae and periodontal disease. Growth of P. gulae was significantly inhibited by clindamycin; this inhibition had a greater effect on type C P. gulae than on type A and B isolates. In contrast, the IFN-α formulation inhibited the expression of IL-1β and COX-2 elicited by type A and B isolates, but not that elicited by type C isolates. Furthermore, periodontal recovery was promoted by the administration of both clindamycin and IFN-α formulation to dogs undergoing periodontal treatment; moreover, this combined treatment reduced the number of FimA genotypes in oral specimens from treated dogs. These results suggest that a combination of clindamycin and IFN-α formulation inhibit P. gulae virulence and thus may be effective for the prevention of periodontal disease induced by P. gulae.",2020 Feb 20,"['Nomura, Ryota', 'Inaba, Hiroaki', 'Yasuda, Hidemi', 'Shirai, Mitsuyuki', 'Kato, Yukio', 'Murakami, Masaru', 'Iwashita, Naoki', 'Shirahata, So', 'Yoshida, Sho', 'Matayoshi, Saaya', 'Yasuda, Junya', 'Arai, Nobuaki', 'Asai, Fumitoshi', 'Matsumoto-Nakano, Michiyo', 'Nakano, Kazuhiko']",Sci Rep,,,False
fad068abaa998641db5de8113fced6b3ef3d613f,PMC,Inhibition of Porphyromonas gulae and periodontal disease in dogs by a combination of clindamycin and interferon alpha,http://dx.doi.org/10.1038/s41598-020-59730-9,PMC7033253,32080231,CC BY,"Porphyromonas gulae is a major periodontal pathogen in dogs, which can be transmitted to their owners. A major virulence factor of P. gulae consists of a 41-kDa filamentous appendage (FimA) on the cell surface, which is classified into three genotypes: A, B, and C. Thus far, inhibition of periodontal disease in dogs remains difficult. The present study assessed the inhibitory effects of a combination of clindamycin and interferon alpha (IFN-α) formulation against P. gulae and periodontal disease. Growth of P. gulae was significantly inhibited by clindamycin; this inhibition had a greater effect on type C P. gulae than on type A and B isolates. In contrast, the IFN-α formulation inhibited the expression of IL-1β and COX-2 elicited by type A and B isolates, but not that elicited by type C isolates. Furthermore, periodontal recovery was promoted by the administration of both clindamycin and IFN-α formulation to dogs undergoing periodontal treatment; moreover, this combined treatment reduced the number of FimA genotypes in oral specimens from treated dogs. These results suggest that a combination of clindamycin and IFN-α formulation inhibit P. gulae virulence and thus may be effective for the prevention of periodontal disease induced by P. gulae.",2020 Feb 20,"['Nomura, Ryota', 'Inaba, Hiroaki', 'Yasuda, Hidemi', 'Shirai, Mitsuyuki', 'Kato, Yukio', 'Murakami, Masaru', 'Iwashita, Naoki', 'Shirahata, So', 'Yoshida, Sho', 'Matayoshi, Saaya', 'Yasuda, Junya', 'Arai, Nobuaki', 'Asai, Fumitoshi', 'Matsumoto-Nakano, Michiyo', 'Nakano, Kazuhiko']",Sci Rep,,,True
61dbde818b21b253a6656b32d30b0dfa2bf0e234,PMC,"2019 novel coronavirus of pneumonia in Wuhan, China: emerging attack and management strategies",http://dx.doi.org/10.1186/s40169-020-00271-z,PMC7033263,32078069,CC BY,"An ongoing outbreak of 2019-nCoV pneumonia was first identified in Wuhan, Hubei province, China at the end of 2019. With the spread of the new coronavirus accelerating, person-to-person transmission in family homes or hospitals, and intercity spread of 2019-nCoV occurred. At least 40,261 cases confirmed, 23,589 cases suspected, 909 cases death and 3444 cases cured in China and worldwide 24 countries confirmed 383 cases being diagnosed, 1 case death in February 10th, 2020. At present, the mortality of 2019-nCoV in China is 2.3%, compared with 9.6% of SARS and 34.4% of MERS reported by WHO. It seems the new virus is not as fatal as many people thought. Chinese authorities improved surveillance network, made the laboratory be able to recognize the outbreak within a few weeks and announced the virus genome that provide efficient epidemiological control. More comprehensive information is required to understand 2019-nCoV feature, the epidemiology of origin and spreading, and the clinical phenomina. According to the current status, blocking transmission, isolation, protection, and alternative medication are the urgent management strategies against 2019-nCoV.",2020 Feb 20,"['She, Jun', 'Jiang, Jinjun', 'Ye, Ling', 'Hu, Lijuan', 'Bai, Chunxue', 'Song, Yuanlin']",Clin Transl Med,,,True
74e492f5464ab2ba5cc8d99b33223b6bc71956d8,PMC,Complete Genome Sequences of Five Human Coronavirus NL63 Strains Causing Respiratory Illness in Hospitalized Children in China,http://dx.doi.org/10.1128/MRA.01597-19,PMC7033275,32079638,CC BY,"We report the complete genome sequences of five human coronavirus NL63 (HCoV-NL63) strains obtained using next-generation sequencing. The five HCoV-NL63 strains were obtained from hospitalized children with severe acute respiratory infection detected in Guangdong, China. This study provides several complete genomes of HCoV-NL63 and improves our understanding of HCoV-NL63 evolution in China.",2020 Feb 20,"['Zhang, Lu', 'Gan, Mian', 'Zhang, Zhaoyong', 'Li, Xin', 'Liu, Wenkuan', 'Zhu, Airu', 'Sun, Jing', 'Li, Fang', 'Wang, Yanqun', 'Zhang, Fuchun', 'Zhao, Jingxian', 'Zhou, Rong', 'Zhao, Jincun']",Microbiol Resour Announc,,,True
9267b60cb1ef8cf0cff3abb351e73dac5d7d7dea,PMC,HIV-1 did not contribute to the 2019-nCoV genome,http://dx.doi.org/10.1080/22221751.2020.1727299,PMC7033698,32056509,CC BY,,2020 Feb 14,"['Xiao, Chuan', 'Li, Xiaojun', 'Liu, Shuying', 'Sang, Yongming', 'Gao, Shou-Jiang', 'Gao, Feng']",Emerg Microbes Infect,,,True
aa8d35501e36393df4a38d6c5ec187c7b1710a94,PMC,"An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies",http://dx.doi.org/10.1080/22221751.2020.1723441,PMC7033706,32005086,CC BY,,2020 Jan 31,"['Jiang, Shibo', 'Du, Lanying', 'Shi, Zhengli']",Emerg Microbes Infect,,,True
52dfa9fbd6dcf7c51fac5cb85a88fb154506a722,PMC,RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak,http://dx.doi.org/10.1080/22221751.2020.1725399,PMC7033720,32020836,CC BY,"From December 2019, an outbreak of unusual pneumonia was reported in Wuhan with many cases linked to Huanan Seafood Market that sells seafood as well as live exotic animals. We investigated two patients who developed acute respiratory syndromes after independent contact history with this market. The two patients shared common clinical features including fever, cough, and multiple ground-glass opacities in the bilateral lung field with patchy infiltration. Here, we highlight the use of a low-input metagenomic next-generation sequencing (mNGS) approach on RNA extracted from bronchoalveolar lavage fluid (BALF). It rapidly identified a novel coronavirus (named 2019-nCoV according to World Health Organization announcement) which was the sole pathogens in the sample with very high abundance level (1.5% and 0.62% of total RNA sequenced). The entire viral genome is 29,881 nt in length (GenBank MN988668 and MN988669, Sequence Read Archive database Bioproject accession PRJNA601736) and is classified into β-coronavirus genus. Phylogenetic analysis indicates that 2019-nCoV is close to coronaviruses (CoVs) circulating in Rhinolophus (Horseshoe bats), such as 98.7% nucleotide identity to partial RdRp gene of bat coronavirus strain BtCoV/4991 (GenBank KP876546, 370 nt sequence of RdRp and lack of other genome sequence) and 87.9% nucleotide identity to bat coronavirus strain bat-SL-CoVZC45 and bat-SL-CoVZXC21. Evolutionary analysis based on ORF1a/1b, S, and N genes also suggests 2019-nCoV is more likely a novel CoV independently introduced from animals to humans.",2020 Feb 5,"['Chen, Liangjun', 'Liu, Weiyong', 'Zhang, Qi', 'Xu, Ke', 'Ye, Guangming', 'Wu, Weichen', 'Sun, Ziyong', 'Liu, Fang', 'Wu, Kailang', 'Zhong, Bo', 'Mei, Yi', 'Zhang, Wenxia', 'Chen, Yu', 'Li, Yirong', 'Shi, Mang', 'Lan, Ke', 'Liu, Yingle']",Emerg Microbes Infect,,,True
b50c31a428792413355bec3fe2f5eaa30e73fefe,PMC,Characteristics of fever and response to antipyretic therapy in military personnel with adenovirus-positive community-acquired pneumonia,http://dx.doi.org/10.1186/s40779-020-00235-x,PMC7033854,32079545,CC BY,"BACKGROUND: In 2014, an outbreak of adenoviral pneumonia occurred in the Korean military training center. However, there are limited data on the characteristics of the fever and its response to antipyretic therapy in immunocompetent adults with adenovirus-positive community-acquired pneumonia (CAP). METHODS: The medical records of the patients who were admitted to the Armed Forces Chuncheon Hospital for the treatment of CAP between January 2014 and December 2016 were retrospectively analyzed. The patients were divided into three groups, namely, the adenovirus-positive (Adv) group, the adenovirus-negative (Non-Adv) group and the unknown pathogen group, according to the results of a polymerase chain reaction (PCR) test and sputum culture used to measure adenovirus and other bacteria or viruses in respiratory specimens. We evaluated and compared the demographics, clinicolaboratory findings and radiological findings upon admission between the two groups. RESULTS: Out of the 251 military personnel with CAP during the study periods, 67 were classified into the Adv group, while 134 were classified into the Non-Adv group and 50 were classified into the unknown pathogen group. The patients in the Adv group had a longer duration of fever after admission (3.2 ± 1.6 vs. 1.9 ± 1.2 vs. 2.2 ± 1.5 days, P = 0.018) and symptom onset (5.8 ± 2.2 vs. 3.9 ± 2.5 vs. 3.7 ± 2.0 days, P = 0.006) than patients in the Non-Adv and unknown pathogen groups, respectively. The patients in the Adv group had a higher mean temperature at admission (37.8 ± 0.3 vs. 37.3 ± 0.3 vs. 37.3 ± 0.3, P = 0.005), and more patients were observed over 40 and 39 to 40(14.9% vs. 2.2% vs. 4.0%, 35.8% vs. 3.7% vs. 6.0%, P <  0.001) than those in the Non-Adv and unknown pathogen groups, respectively. The Adv group more commonly had no response or exhibited adverse events after antipyretic treatment compared to the Non-Adv group (17.9% vs. 1.5%, 35.0% vs. 4.3%, P <  0.001, P = 0.05, respectively). In addition, the time from admission to overall clinical stabilization was significantly longer in the patients in the Adv group than in those in the Non-Adv group (4.3 ± 2.8 vs. 2.9 ± 1.8 days, P = 0.034, respectively). Furthermore, no significant difference in the length of hospital stay was observed between the two groups, and no patient died in either group. CONCLUSION: In this study, Adv-positive CAP in immunocompetent military personnel patients had distinct fever characteristics and responses to antipyretic treatment.",2020 Feb 21,"['Yoo, Hongseok', 'Oh, Jimi', 'Park, Chul']",Mil Med Res,,,True
0188acc1eba8c0a3adef55aeada7de552cf855be,PMC,"Discovery of a subgenotype of human coronavirus NL63 associated with severe lower respiratory tract infection in China, 2018",http://dx.doi.org/10.1080/22221751.2020.1717999,PMC7034077,31996093,CC BY,"Human coronavirus NL63 (HCoV-NL63) is primarily associated with common cold in children, elderly and immunocompromised individuals. Outbreaks caused by HCoV-NL63 are rare. Here we report a cluster of HCoV-NL63 cases with severe lower respiratory tract infection that arose in Guangzhou, China, in 2018. Twenty-three hospitalized children were confirmed to be HCoV-NL63 positive, and most of whom were hospitalized with severe pneumonia or acute bronchitis. Whole genomes of HCoV-NL63 were obtained using next-generation sequencing. Phylogenetic and single amino acid polymorphism analyses showed that this outbreak was associated with two subgenotypes (C3 and B) of HCoV-NL63. Half of patients were identified to be related to a new subgenotype C3. One unique amino acid mutation at I507 L in spike protein receptor binding domain (RBD) was detected, which segregated this subgenotype C3 from other known subgenotypes. Pseudotyped virus bearing the I507 L mutation in RBD showed enhanced entry into host cells as compared to the prototype virus. This study proved that HCoV-NL63 was undergoing continuous mutation and has the potential to cause severe lower respiratory disease in humans.",2020 Jan 29,"['Wang, Yanqun', 'Li, Xin', 'Liu, Wenkuan', 'Gan, Mian', 'Zhang, Lu', 'Wang, Jin', 'Zhang, Zhaoyong', 'Zhu, Airu', 'Li, Fang', 'Sun, Jing', 'Zhang, Guoxian', 'Zhuang, Zhen', 'Luo, Jiaying', 'Chen, Dehui', 'Qiu, Shuyan', 'Zhang, Li', 'Xu, Duo', 'Mok, Chris Ka Pun', 'Zhang, Fuchun', 'Zhao, Jingxian', 'Zhou, Rong', 'Zhao, Jincun']",Emerg Microbes Infect,,,True
2f38704ef0009750d4c48d1cd7ac81e898023527,PMC,Multiple Family Members With Delayed Cord Separtion and Combined Immunodeficiency With Novel Mutation in IKBKB,http://dx.doi.org/10.3389/fped.2020.00009,PMC7034298,32117824,CC BY,"Background: Inhibitor of kappa kinase 2 (IKK2) deficiency is a recently described combined immunodeficiency. It undermines the nuclear factor-kappa B (NF-κB) activation pathway. Methods: The clinical and immunological data of four patients diagnosed with combined immunodeficiency (CID) from two related Saudi families were collected. Autozygosity mapping of all available members and whole exome sequencing of the index case were performed to define the genetic etiology. Results: The patients had early onset (2–4 months of age) severe infections caused by viruses, bacteria, mycobacteria, and fungi. They all had hypogammaglobulinemia and low absolute lymphocyte count. Their lymphocytes failed to respond to PHA mitogen stimulation. A novel homozygous non-sense mutation in the IKBKB gene, c.850C>T (p. Arg284*) was identified in the index patient and segregated with the disease in the rest of the family. He underwent hematopoietic stem cell transplantation (HSCT) from a fully matched sibling with no conditioning. The other three patients succumbed to their disease. Interestingly, all patients had delayed umbilical cord separation. Conclusion: IKK2 deficiency causes CID with high mortality. Immune reconstitution with HSCT should be considered as early as possible. Delayed umbilical cord separation in CID patients may be a clue to IKK2 deficiency.",2020 Feb 14,"['Alsum, Zobaida', 'AlZahrani, Mofareh S.', 'Al-Mousa, Hamoud', 'Alkhamis, Nouf', 'Alsalemi, Abdulkareem A.', 'Shamseldin, Hanan E.', 'Alkuraya, Fowzan S.', 'Alangari, Abdullah A.']",Front Pediatr,,,True
170fc4f86244f8f795de48b349db6759add5a834,PMC,Emergency nurses’ perceptions regarding the risks appraisal of the threat of the emerging infectious disease situation in emergency departments,http://dx.doi.org/10.1080/17482631.2020.1718468,PMC7034460,31975652,CC BY,"Purpose: Emerging infectious diseases are considered as a pressing challenge to global public health. Throughout public health response to emerging infectious diseases, emergency nurses are situated at the forefront of the healthcare system. The present study has explored emergency nurses’ perceptions regarding the risks appraisal of the threat of the emerging infectious disease situation in emergency department context. Methods: The present study used a qualitative descriptive approach. A purposive sampling method was employed to recruit emergency nurses who worked in public hospitals in Hong Kong. Semi-structured interviews were conducted to 24 emergency nurses. The data were interpreted using a thematic analysis strategy. Results: Five overarching themes emerged from the data: (1) the novelty of an emerging infectious disease, (2) the severity of an emerging infectious disease, (3) the proximity to an emerging infectious disease, (4) the complexity of an emerging infectious disease situation, and (5) the response levels towards an emerging infectious disease situation. Conclusion: It is anticipated that the information may help to predict the attitudes and behaviours of emergency nurses in future impending epidemic events, enhancing emergency nurses’ preparedness towards in such situations. Abbreviations: EID: Emerging infectious disease; ED: Emergency department; SARS: Severe acute respiratory syndrome; MERS: Middle East respiratory syndrome; WHO: World Health Organization; RN: Registered nurse; APN: Advanced practice nurse; NO: Nursing officer",2020 Jan 24,"['Lam, Stanley Kam Ki', 'Kwong, Enid Wai Yung', 'Hung, Maria Shuk Yu', 'Chien, Wai Tong']",Int J Qual Stud Health Well-being,,,True
52d222becd8912fcd1a81cf956a18f88b738c2ee,PMC,Long-term trends in seasonality of mortality in urban Madagascar: the role of the epidemiological transition,http://dx.doi.org/10.1080/16549716.2020.1717411,PMC7034494,32027239,CC BY,"Background: Seasonal patterns of mortality have been identified in Sub-Saharan Africa but their changes over time are not well documented. Objective: Based on death notification data from Antananarivo, the capital city of Madagascar, this study assesses seasonal patterns of all-cause and cause-specific mortality by age groups and evaluates how these patterns changed over the period 1976–2015. Methods: Monthly numbers of deaths by cause were obtained from death registers maintained by the Municipal Hygiene Office in charge of verifying deaths before the issuance of burial permits. Generalized Additive Mixed regression models (GAMM) were used to test for seasonality in mortality and its changes over the last four decades, controlling for long-term trends in mortality. Results: Among children, risks of dying were the highest during the hot and rainy season, but seasonality in child mortality has significantly declined since the mid-1970s, as a result of declines in the burden of infectious diseases and nutritional deficiencies. In adults aged 60 and above, all-cause mortality rates are the highest in the dry and cold season, due to peaks in cardiovascular diseases, with little change over time. Overall, changes in the seasonality of all-cause mortality have been driven by shifts in the hierarchy of causes of death, while changes in the seasonality within broad categories of causes of death have been modest. Conclusion: Shifts in disease patterns brought about by the epidemiological transition, rather than changes in seasonal variation in cause-specific mortality, are the main drivers of trends in the seasonality of all-cause mortality.",2020 Feb 6,"['Schlüter, Benjamin-Samuel', 'Masquelier, Bruno', 'Metcalf, C. Jessica E.', 'Rasoanomenjanahary, Anjarasoa']",Glob Health Action,,,True
cc9c7b2c3bf9ccf4122153d1d1c4269c902cb0a1,PMC,Long-term trends in seasonality of mortality in urban Madagascar: the role of the epidemiological transition,http://dx.doi.org/10.1080/16549716.2020.1717411,PMC7034494,32027239,CC BY,"Background: Seasonal patterns of mortality have been identified in Sub-Saharan Africa but their changes over time are not well documented. Objective: Based on death notification data from Antananarivo, the capital city of Madagascar, this study assesses seasonal patterns of all-cause and cause-specific mortality by age groups and evaluates how these patterns changed over the period 1976–2015. Methods: Monthly numbers of deaths by cause were obtained from death registers maintained by the Municipal Hygiene Office in charge of verifying deaths before the issuance of burial permits. Generalized Additive Mixed regression models (GAMM) were used to test for seasonality in mortality and its changes over the last four decades, controlling for long-term trends in mortality. Results: Among children, risks of dying were the highest during the hot and rainy season, but seasonality in child mortality has significantly declined since the mid-1970s, as a result of declines in the burden of infectious diseases and nutritional deficiencies. In adults aged 60 and above, all-cause mortality rates are the highest in the dry and cold season, due to peaks in cardiovascular diseases, with little change over time. Overall, changes in the seasonality of all-cause mortality have been driven by shifts in the hierarchy of causes of death, while changes in the seasonality within broad categories of causes of death have been modest. Conclusion: Shifts in disease patterns brought about by the epidemiological transition, rather than changes in seasonal variation in cause-specific mortality, are the main drivers of trends in the seasonality of all-cause mortality.",2020 Feb 6,"['Schlüter, Benjamin-Samuel', 'Masquelier, Bruno', 'Metcalf, C. Jessica E.', 'Rasoanomenjanahary, Anjarasoa']",Glob Health Action,,,False
9f6c32146a34cb8bf7ca8f3fe3417d315d6baf71,PMC,Long-term trends in seasonality of mortality in urban Madagascar: the role of the epidemiological transition,http://dx.doi.org/10.1080/16549716.2020.1717411,PMC7034494,32027239,CC BY,"Background: Seasonal patterns of mortality have been identified in Sub-Saharan Africa but their changes over time are not well documented. Objective: Based on death notification data from Antananarivo, the capital city of Madagascar, this study assesses seasonal patterns of all-cause and cause-specific mortality by age groups and evaluates how these patterns changed over the period 1976–2015. Methods: Monthly numbers of deaths by cause were obtained from death registers maintained by the Municipal Hygiene Office in charge of verifying deaths before the issuance of burial permits. Generalized Additive Mixed regression models (GAMM) were used to test for seasonality in mortality and its changes over the last four decades, controlling for long-term trends in mortality. Results: Among children, risks of dying were the highest during the hot and rainy season, but seasonality in child mortality has significantly declined since the mid-1970s, as a result of declines in the burden of infectious diseases and nutritional deficiencies. In adults aged 60 and above, all-cause mortality rates are the highest in the dry and cold season, due to peaks in cardiovascular diseases, with little change over time. Overall, changes in the seasonality of all-cause mortality have been driven by shifts in the hierarchy of causes of death, while changes in the seasonality within broad categories of causes of death have been modest. Conclusion: Shifts in disease patterns brought about by the epidemiological transition, rather than changes in seasonal variation in cause-specific mortality, are the main drivers of trends in the seasonality of all-cause mortality.",2020 Feb 6,"['Schlüter, Benjamin-Samuel', 'Masquelier, Bruno', 'Metcalf, C. Jessica E.', 'Rasoanomenjanahary, Anjarasoa']",Glob Health Action,,,False
f646e9089878460f2724febaf5b69270c26a0a25,PMC,Long-term trends in seasonality of mortality in urban Madagascar: the role of the epidemiological transition,http://dx.doi.org/10.1080/16549716.2020.1717411,PMC7034494,32027239,CC BY,"Background: Seasonal patterns of mortality have been identified in Sub-Saharan Africa but their changes over time are not well documented. Objective: Based on death notification data from Antananarivo, the capital city of Madagascar, this study assesses seasonal patterns of all-cause and cause-specific mortality by age groups and evaluates how these patterns changed over the period 1976–2015. Methods: Monthly numbers of deaths by cause were obtained from death registers maintained by the Municipal Hygiene Office in charge of verifying deaths before the issuance of burial permits. Generalized Additive Mixed regression models (GAMM) were used to test for seasonality in mortality and its changes over the last four decades, controlling for long-term trends in mortality. Results: Among children, risks of dying were the highest during the hot and rainy season, but seasonality in child mortality has significantly declined since the mid-1970s, as a result of declines in the burden of infectious diseases and nutritional deficiencies. In adults aged 60 and above, all-cause mortality rates are the highest in the dry and cold season, due to peaks in cardiovascular diseases, with little change over time. Overall, changes in the seasonality of all-cause mortality have been driven by shifts in the hierarchy of causes of death, while changes in the seasonality within broad categories of causes of death have been modest. Conclusion: Shifts in disease patterns brought about by the epidemiological transition, rather than changes in seasonal variation in cause-specific mortality, are the main drivers of trends in the seasonality of all-cause mortality.",2020 Feb 6,"['Schlüter, Benjamin-Samuel', 'Masquelier, Bruno', 'Metcalf, C. Jessica E.', 'Rasoanomenjanahary, Anjarasoa']",Glob Health Action,,,False
cc15d22c79a76e8d6c70f3d1f607100d83aa27b2,PMC,Long-term trends in seasonality of mortality in urban Madagascar: the role of the epidemiological transition,http://dx.doi.org/10.1080/16549716.2020.1717411,PMC7034494,32027239,CC BY,"Background: Seasonal patterns of mortality have been identified in Sub-Saharan Africa but their changes over time are not well documented. Objective: Based on death notification data from Antananarivo, the capital city of Madagascar, this study assesses seasonal patterns of all-cause and cause-specific mortality by age groups and evaluates how these patterns changed over the period 1976–2015. Methods: Monthly numbers of deaths by cause were obtained from death registers maintained by the Municipal Hygiene Office in charge of verifying deaths before the issuance of burial permits. Generalized Additive Mixed regression models (GAMM) were used to test for seasonality in mortality and its changes over the last four decades, controlling for long-term trends in mortality. Results: Among children, risks of dying were the highest during the hot and rainy season, but seasonality in child mortality has significantly declined since the mid-1970s, as a result of declines in the burden of infectious diseases and nutritional deficiencies. In adults aged 60 and above, all-cause mortality rates are the highest in the dry and cold season, due to peaks in cardiovascular diseases, with little change over time. Overall, changes in the seasonality of all-cause mortality have been driven by shifts in the hierarchy of causes of death, while changes in the seasonality within broad categories of causes of death have been modest. Conclusion: Shifts in disease patterns brought about by the epidemiological transition, rather than changes in seasonal variation in cause-specific mortality, are the main drivers of trends in the seasonality of all-cause mortality.",2020 Feb 6,"['Schlüter, Benjamin-Samuel', 'Masquelier, Bruno', 'Metcalf, C. Jessica E.', 'Rasoanomenjanahary, Anjarasoa']",Glob Health Action,,,False
8be9f1b18de44f61ed5a342dac1e47d12c943dca,PMC,Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation,http://dx.doi.org/10.1371/journal.pcbi.1007587,PMC7034926,32040506,CC BY,"Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have been targeted. Identification of host factors on a pan-pathogen level, i.e., genes that are crucial for the replication of a diverse group of pathogens has received relatively little attention, despite the fact that such common host factors would be highly relevant, for instance, for devising broad-spectrum anti-pathogenic drugs. Here, we present a novel two-stage procedure for the identification of host factors involved in the replication of different viruses using a combination of random effects models and Markov random walks on a functional interaction network. We first infer candidate genes by jointly analyzing multiple perturbations screens while at the same time adjusting for high variance inherent in these screens. Subsequently the inferred estimates are spread across a network of functional interactions thereby allowing for the analysis of missing genes in the biological studies, smoothing the effect sizes of previously found host factors, and considering a priori pathway information defined over edges of the network. We applied the procedure to RNAi screening data of four different positive-sense single-stranded RNA viruses, Hepatitis C virus, Chikungunya virus, Dengue virus and Severe acute respiratory syndrome coronavirus, and detected novel host factors, including UBC, PLCG1, and DYRK1B, which are predicted to significantly impact the replication cycles of these viruses. We validated the detected host factors experimentally using pharmacological inhibition and an additional siRNA screen and found that some of the predicted host factors indeed influence the replication of these pathogens.",2020 Feb 10,"['Dirmeier, Simon', 'Dächert, Christopher', 'van Hemert, Martijn', 'Tas, Ali', 'Ogando, Natacha S.', 'van Kuppeveld, Frank', 'Bartenschlager, Ralf', 'Kaderali, Lars', 'Binder, Marco', 'Beerenwinkel, Niko']",PLoS Comput Biol,,,True
746ffda232ee86701bad4e0a148cfc9ad8542bc2,PMC,Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation,http://dx.doi.org/10.1371/journal.pcbi.1007587,PMC7034926,32040506,CC BY,"Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have been targeted. Identification of host factors on a pan-pathogen level, i.e., genes that are crucial for the replication of a diverse group of pathogens has received relatively little attention, despite the fact that such common host factors would be highly relevant, for instance, for devising broad-spectrum anti-pathogenic drugs. Here, we present a novel two-stage procedure for the identification of host factors involved in the replication of different viruses using a combination of random effects models and Markov random walks on a functional interaction network. We first infer candidate genes by jointly analyzing multiple perturbations screens while at the same time adjusting for high variance inherent in these screens. Subsequently the inferred estimates are spread across a network of functional interactions thereby allowing for the analysis of missing genes in the biological studies, smoothing the effect sizes of previously found host factors, and considering a priori pathway information defined over edges of the network. We applied the procedure to RNAi screening data of four different positive-sense single-stranded RNA viruses, Hepatitis C virus, Chikungunya virus, Dengue virus and Severe acute respiratory syndrome coronavirus, and detected novel host factors, including UBC, PLCG1, and DYRK1B, which are predicted to significantly impact the replication cycles of these viruses. We validated the detected host factors experimentally using pharmacological inhibition and an additional siRNA screen and found that some of the predicted host factors indeed influence the replication of these pathogens.",2020 Feb 10,"['Dirmeier, Simon', 'Dächert, Christopher', 'van Hemert, Martijn', 'Tas, Ali', 'Ogando, Natacha S.', 'van Kuppeveld, Frank', 'Bartenschlager, Ralf', 'Kaderali, Lars', 'Binder, Marco', 'Beerenwinkel, Niko']",PLoS Comput Biol,,,False
054bc6dfc8aa4286237c23dc0aafc10fc15b104a,PMC,Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation,http://dx.doi.org/10.1371/journal.pcbi.1007587,PMC7034926,32040506,CC BY,"Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have been targeted. Identification of host factors on a pan-pathogen level, i.e., genes that are crucial for the replication of a diverse group of pathogens has received relatively little attention, despite the fact that such common host factors would be highly relevant, for instance, for devising broad-spectrum anti-pathogenic drugs. Here, we present a novel two-stage procedure for the identification of host factors involved in the replication of different viruses using a combination of random effects models and Markov random walks on a functional interaction network. We first infer candidate genes by jointly analyzing multiple perturbations screens while at the same time adjusting for high variance inherent in these screens. Subsequently the inferred estimates are spread across a network of functional interactions thereby allowing for the analysis of missing genes in the biological studies, smoothing the effect sizes of previously found host factors, and considering a priori pathway information defined over edges of the network. We applied the procedure to RNAi screening data of four different positive-sense single-stranded RNA viruses, Hepatitis C virus, Chikungunya virus, Dengue virus and Severe acute respiratory syndrome coronavirus, and detected novel host factors, including UBC, PLCG1, and DYRK1B, which are predicted to significantly impact the replication cycles of these viruses. We validated the detected host factors experimentally using pharmacological inhibition and an additional siRNA screen and found that some of the predicted host factors indeed influence the replication of these pathogens.",2020 Feb 10,"['Dirmeier, Simon', 'Dächert, Christopher', 'van Hemert, Martijn', 'Tas, Ali', 'Ogando, Natacha S.', 'van Kuppeveld, Frank', 'Bartenschlager, Ralf', 'Kaderali, Lars', 'Binder, Marco', 'Beerenwinkel, Niko']",PLoS Comput Biol,,,False
3f950076ddcc14669519255515cb454a8689acda,PMC,Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation,http://dx.doi.org/10.1371/journal.pcbi.1007587,PMC7034926,32040506,CC BY,"Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have been targeted. Identification of host factors on a pan-pathogen level, i.e., genes that are crucial for the replication of a diverse group of pathogens has received relatively little attention, despite the fact that such common host factors would be highly relevant, for instance, for devising broad-spectrum anti-pathogenic drugs. Here, we present a novel two-stage procedure for the identification of host factors involved in the replication of different viruses using a combination of random effects models and Markov random walks on a functional interaction network. We first infer candidate genes by jointly analyzing multiple perturbations screens while at the same time adjusting for high variance inherent in these screens. Subsequently the inferred estimates are spread across a network of functional interactions thereby allowing for the analysis of missing genes in the biological studies, smoothing the effect sizes of previously found host factors, and considering a priori pathway information defined over edges of the network. We applied the procedure to RNAi screening data of four different positive-sense single-stranded RNA viruses, Hepatitis C virus, Chikungunya virus, Dengue virus and Severe acute respiratory syndrome coronavirus, and detected novel host factors, including UBC, PLCG1, and DYRK1B, which are predicted to significantly impact the replication cycles of these viruses. We validated the detected host factors experimentally using pharmacological inhibition and an additional siRNA screen and found that some of the predicted host factors indeed influence the replication of these pathogens.",2020 Feb 10,"['Dirmeier, Simon', 'Dächert, Christopher', 'van Hemert, Martijn', 'Tas, Ali', 'Ogando, Natacha S.', 'van Kuppeveld, Frank', 'Bartenschlager, Ralf', 'Kaderali, Lars', 'Binder, Marco', 'Beerenwinkel, Niko']",PLoS Comput Biol,,,False
33501088254357a2932ff4ed14c0e14431ea1b86,PMC,Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation,http://dx.doi.org/10.1371/journal.pcbi.1007587,PMC7034926,32040506,CC BY,"Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have been targeted. Identification of host factors on a pan-pathogen level, i.e., genes that are crucial for the replication of a diverse group of pathogens has received relatively little attention, despite the fact that such common host factors would be highly relevant, for instance, for devising broad-spectrum anti-pathogenic drugs. Here, we present a novel two-stage procedure for the identification of host factors involved in the replication of different viruses using a combination of random effects models and Markov random walks on a functional interaction network. We first infer candidate genes by jointly analyzing multiple perturbations screens while at the same time adjusting for high variance inherent in these screens. Subsequently the inferred estimates are spread across a network of functional interactions thereby allowing for the analysis of missing genes in the biological studies, smoothing the effect sizes of previously found host factors, and considering a priori pathway information defined over edges of the network. We applied the procedure to RNAi screening data of four different positive-sense single-stranded RNA viruses, Hepatitis C virus, Chikungunya virus, Dengue virus and Severe acute respiratory syndrome coronavirus, and detected novel host factors, including UBC, PLCG1, and DYRK1B, which are predicted to significantly impact the replication cycles of these viruses. We validated the detected host factors experimentally using pharmacological inhibition and an additional siRNA screen and found that some of the predicted host factors indeed influence the replication of these pathogens.",2020 Feb 10,"['Dirmeier, Simon', 'Dächert, Christopher', 'van Hemert, Martijn', 'Tas, Ali', 'Ogando, Natacha S.', 'van Kuppeveld, Frank', 'Bartenschlager, Ralf', 'Kaderali, Lars', 'Binder, Marco', 'Beerenwinkel, Niko']",PLoS Comput Biol,,,False
ba0be43c1d8516c01e5a21767b7ac9d71e296cff,PMC,Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation,http://dx.doi.org/10.1371/journal.pcbi.1007587,PMC7034926,32040506,CC BY,"Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have been targeted. Identification of host factors on a pan-pathogen level, i.e., genes that are crucial for the replication of a diverse group of pathogens has received relatively little attention, despite the fact that such common host factors would be highly relevant, for instance, for devising broad-spectrum anti-pathogenic drugs. Here, we present a novel two-stage procedure for the identification of host factors involved in the replication of different viruses using a combination of random effects models and Markov random walks on a functional interaction network. We first infer candidate genes by jointly analyzing multiple perturbations screens while at the same time adjusting for high variance inherent in these screens. Subsequently the inferred estimates are spread across a network of functional interactions thereby allowing for the analysis of missing genes in the biological studies, smoothing the effect sizes of previously found host factors, and considering a priori pathway information defined over edges of the network. We applied the procedure to RNAi screening data of four different positive-sense single-stranded RNA viruses, Hepatitis C virus, Chikungunya virus, Dengue virus and Severe acute respiratory syndrome coronavirus, and detected novel host factors, including UBC, PLCG1, and DYRK1B, which are predicted to significantly impact the replication cycles of these viruses. We validated the detected host factors experimentally using pharmacological inhibition and an additional siRNA screen and found that some of the predicted host factors indeed influence the replication of these pathogens.",2020 Feb 10,"['Dirmeier, Simon', 'Dächert, Christopher', 'van Hemert, Martijn', 'Tas, Ali', 'Ogando, Natacha S.', 'van Kuppeveld, Frank', 'Bartenschlager, Ralf', 'Kaderali, Lars', 'Binder, Marco', 'Beerenwinkel, Niko']",PLoS Comput Biol,,,False
5b63cc870fbd0939825731e6b589ff08e808cb7a,PMC,Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation,http://dx.doi.org/10.1371/journal.pcbi.1007587,PMC7034926,32040506,CC BY,"Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have been targeted. Identification of host factors on a pan-pathogen level, i.e., genes that are crucial for the replication of a diverse group of pathogens has received relatively little attention, despite the fact that such common host factors would be highly relevant, for instance, for devising broad-spectrum anti-pathogenic drugs. Here, we present a novel two-stage procedure for the identification of host factors involved in the replication of different viruses using a combination of random effects models and Markov random walks on a functional interaction network. We first infer candidate genes by jointly analyzing multiple perturbations screens while at the same time adjusting for high variance inherent in these screens. Subsequently the inferred estimates are spread across a network of functional interactions thereby allowing for the analysis of missing genes in the biological studies, smoothing the effect sizes of previously found host factors, and considering a priori pathway information defined over edges of the network. We applied the procedure to RNAi screening data of four different positive-sense single-stranded RNA viruses, Hepatitis C virus, Chikungunya virus, Dengue virus and Severe acute respiratory syndrome coronavirus, and detected novel host factors, including UBC, PLCG1, and DYRK1B, which are predicted to significantly impact the replication cycles of these viruses. We validated the detected host factors experimentally using pharmacological inhibition and an additional siRNA screen and found that some of the predicted host factors indeed influence the replication of these pathogens.",2020 Feb 10,"['Dirmeier, Simon', 'Dächert, Christopher', 'van Hemert, Martijn', 'Tas, Ali', 'Ogando, Natacha S.', 'van Kuppeveld, Frank', 'Bartenschlager, Ralf', 'Kaderali, Lars', 'Binder, Marco', 'Beerenwinkel, Niko']",PLoS Comput Biol,,,False
2258c31ef091905d7319d5c894bd045f20cc8613,PMC,Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation,http://dx.doi.org/10.1371/journal.pcbi.1007587,PMC7034926,32040506,CC BY,"Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have been targeted. Identification of host factors on a pan-pathogen level, i.e., genes that are crucial for the replication of a diverse group of pathogens has received relatively little attention, despite the fact that such common host factors would be highly relevant, for instance, for devising broad-spectrum anti-pathogenic drugs. Here, we present a novel two-stage procedure for the identification of host factors involved in the replication of different viruses using a combination of random effects models and Markov random walks on a functional interaction network. We first infer candidate genes by jointly analyzing multiple perturbations screens while at the same time adjusting for high variance inherent in these screens. Subsequently the inferred estimates are spread across a network of functional interactions thereby allowing for the analysis of missing genes in the biological studies, smoothing the effect sizes of previously found host factors, and considering a priori pathway information defined over edges of the network. We applied the procedure to RNAi screening data of four different positive-sense single-stranded RNA viruses, Hepatitis C virus, Chikungunya virus, Dengue virus and Severe acute respiratory syndrome coronavirus, and detected novel host factors, including UBC, PLCG1, and DYRK1B, which are predicted to significantly impact the replication cycles of these viruses. We validated the detected host factors experimentally using pharmacological inhibition and an additional siRNA screen and found that some of the predicted host factors indeed influence the replication of these pathogens.",2020 Feb 10,"['Dirmeier, Simon', 'Dächert, Christopher', 'van Hemert, Martijn', 'Tas, Ali', 'Ogando, Natacha S.', 'van Kuppeveld, Frank', 'Bartenschlager, Ralf', 'Kaderali, Lars', 'Binder, Marco', 'Beerenwinkel, Niko']",PLoS Comput Biol,,,False
80a15b6182cd9f6e0ac59d0e78857fdde6853fcf,PMC,Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation,http://dx.doi.org/10.1371/journal.pcbi.1007587,PMC7034926,32040506,CC BY,"Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have been targeted. Identification of host factors on a pan-pathogen level, i.e., genes that are crucial for the replication of a diverse group of pathogens has received relatively little attention, despite the fact that such common host factors would be highly relevant, for instance, for devising broad-spectrum anti-pathogenic drugs. Here, we present a novel two-stage procedure for the identification of host factors involved in the replication of different viruses using a combination of random effects models and Markov random walks on a functional interaction network. We first infer candidate genes by jointly analyzing multiple perturbations screens while at the same time adjusting for high variance inherent in these screens. Subsequently the inferred estimates are spread across a network of functional interactions thereby allowing for the analysis of missing genes in the biological studies, smoothing the effect sizes of previously found host factors, and considering a priori pathway information defined over edges of the network. We applied the procedure to RNAi screening data of four different positive-sense single-stranded RNA viruses, Hepatitis C virus, Chikungunya virus, Dengue virus and Severe acute respiratory syndrome coronavirus, and detected novel host factors, including UBC, PLCG1, and DYRK1B, which are predicted to significantly impact the replication cycles of these viruses. We validated the detected host factors experimentally using pharmacological inhibition and an additional siRNA screen and found that some of the predicted host factors indeed influence the replication of these pathogens.",2020 Feb 10,"['Dirmeier, Simon', 'Dächert, Christopher', 'van Hemert, Martijn', 'Tas, Ali', 'Ogando, Natacha S.', 'van Kuppeveld, Frank', 'Bartenschlager, Ralf', 'Kaderali, Lars', 'Binder, Marco', 'Beerenwinkel, Niko']",PLoS Comput Biol,,,False
8b5e4c4fab06cff618a42937089c20f419db41a5,PMC,Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation,http://dx.doi.org/10.1371/journal.pcbi.1007587,PMC7034926,32040506,CC BY,"Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have been targeted. Identification of host factors on a pan-pathogen level, i.e., genes that are crucial for the replication of a diverse group of pathogens has received relatively little attention, despite the fact that such common host factors would be highly relevant, for instance, for devising broad-spectrum anti-pathogenic drugs. Here, we present a novel two-stage procedure for the identification of host factors involved in the replication of different viruses using a combination of random effects models and Markov random walks on a functional interaction network. We first infer candidate genes by jointly analyzing multiple perturbations screens while at the same time adjusting for high variance inherent in these screens. Subsequently the inferred estimates are spread across a network of functional interactions thereby allowing for the analysis of missing genes in the biological studies, smoothing the effect sizes of previously found host factors, and considering a priori pathway information defined over edges of the network. We applied the procedure to RNAi screening data of four different positive-sense single-stranded RNA viruses, Hepatitis C virus, Chikungunya virus, Dengue virus and Severe acute respiratory syndrome coronavirus, and detected novel host factors, including UBC, PLCG1, and DYRK1B, which are predicted to significantly impact the replication cycles of these viruses. We validated the detected host factors experimentally using pharmacological inhibition and an additional siRNA screen and found that some of the predicted host factors indeed influence the replication of these pathogens.",2020 Feb 10,"['Dirmeier, Simon', 'Dächert, Christopher', 'van Hemert, Martijn', 'Tas, Ali', 'Ogando, Natacha S.', 'van Kuppeveld, Frank', 'Bartenschlager, Ralf', 'Kaderali, Lars', 'Binder, Marco', 'Beerenwinkel, Niko']",PLoS Comput Biol,,,False
67a3211afe5728fa8b77dff83e360cdfffbfc907,PMC,Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation,http://dx.doi.org/10.1371/journal.pcbi.1007587,PMC7034926,32040506,CC BY,"Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have been targeted. Identification of host factors on a pan-pathogen level, i.e., genes that are crucial for the replication of a diverse group of pathogens has received relatively little attention, despite the fact that such common host factors would be highly relevant, for instance, for devising broad-spectrum anti-pathogenic drugs. Here, we present a novel two-stage procedure for the identification of host factors involved in the replication of different viruses using a combination of random effects models and Markov random walks on a functional interaction network. We first infer candidate genes by jointly analyzing multiple perturbations screens while at the same time adjusting for high variance inherent in these screens. Subsequently the inferred estimates are spread across a network of functional interactions thereby allowing for the analysis of missing genes in the biological studies, smoothing the effect sizes of previously found host factors, and considering a priori pathway information defined over edges of the network. We applied the procedure to RNAi screening data of four different positive-sense single-stranded RNA viruses, Hepatitis C virus, Chikungunya virus, Dengue virus and Severe acute respiratory syndrome coronavirus, and detected novel host factors, including UBC, PLCG1, and DYRK1B, which are predicted to significantly impact the replication cycles of these viruses. We validated the detected host factors experimentally using pharmacological inhibition and an additional siRNA screen and found that some of the predicted host factors indeed influence the replication of these pathogens.",2020 Feb 10,"['Dirmeier, Simon', 'Dächert, Christopher', 'van Hemert, Martijn', 'Tas, Ali', 'Ogando, Natacha S.', 'van Kuppeveld, Frank', 'Bartenschlager, Ralf', 'Kaderali, Lars', 'Binder, Marco', 'Beerenwinkel, Niko']",PLoS Comput Biol,,,False
7a0eec55459d559c64041c24ca368e48b431da19,PMC,Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation,http://dx.doi.org/10.1371/journal.pcbi.1007587,PMC7034926,32040506,CC BY,"Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have been targeted. Identification of host factors on a pan-pathogen level, i.e., genes that are crucial for the replication of a diverse group of pathogens has received relatively little attention, despite the fact that such common host factors would be highly relevant, for instance, for devising broad-spectrum anti-pathogenic drugs. Here, we present a novel two-stage procedure for the identification of host factors involved in the replication of different viruses using a combination of random effects models and Markov random walks on a functional interaction network. We first infer candidate genes by jointly analyzing multiple perturbations screens while at the same time adjusting for high variance inherent in these screens. Subsequently the inferred estimates are spread across a network of functional interactions thereby allowing for the analysis of missing genes in the biological studies, smoothing the effect sizes of previously found host factors, and considering a priori pathway information defined over edges of the network. We applied the procedure to RNAi screening data of four different positive-sense single-stranded RNA viruses, Hepatitis C virus, Chikungunya virus, Dengue virus and Severe acute respiratory syndrome coronavirus, and detected novel host factors, including UBC, PLCG1, and DYRK1B, which are predicted to significantly impact the replication cycles of these viruses. We validated the detected host factors experimentally using pharmacological inhibition and an additional siRNA screen and found that some of the predicted host factors indeed influence the replication of these pathogens.",2020 Feb 10,"['Dirmeier, Simon', 'Dächert, Christopher', 'van Hemert, Martijn', 'Tas, Ali', 'Ogando, Natacha S.', 'van Kuppeveld, Frank', 'Bartenschlager, Ralf', 'Kaderali, Lars', 'Binder, Marco', 'Beerenwinkel, Niko']",PLoS Comput Biol,,,False
e8932f392336c730172233c2ea31ffcf7901cc46,PMC,Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation,http://dx.doi.org/10.1371/journal.pcbi.1007587,PMC7034926,32040506,CC BY,"Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have been targeted. Identification of host factors on a pan-pathogen level, i.e., genes that are crucial for the replication of a diverse group of pathogens has received relatively little attention, despite the fact that such common host factors would be highly relevant, for instance, for devising broad-spectrum anti-pathogenic drugs. Here, we present a novel two-stage procedure for the identification of host factors involved in the replication of different viruses using a combination of random effects models and Markov random walks on a functional interaction network. We first infer candidate genes by jointly analyzing multiple perturbations screens while at the same time adjusting for high variance inherent in these screens. Subsequently the inferred estimates are spread across a network of functional interactions thereby allowing for the analysis of missing genes in the biological studies, smoothing the effect sizes of previously found host factors, and considering a priori pathway information defined over edges of the network. We applied the procedure to RNAi screening data of four different positive-sense single-stranded RNA viruses, Hepatitis C virus, Chikungunya virus, Dengue virus and Severe acute respiratory syndrome coronavirus, and detected novel host factors, including UBC, PLCG1, and DYRK1B, which are predicted to significantly impact the replication cycles of these viruses. We validated the detected host factors experimentally using pharmacological inhibition and an additional siRNA screen and found that some of the predicted host factors indeed influence the replication of these pathogens.",2020 Feb 10,"['Dirmeier, Simon', 'Dächert, Christopher', 'van Hemert, Martijn', 'Tas, Ali', 'Ogando, Natacha S.', 'van Kuppeveld, Frank', 'Bartenschlager, Ralf', 'Kaderali, Lars', 'Binder, Marco', 'Beerenwinkel, Niko']",PLoS Comput Biol,,,False
7dedea169a8f7fbec2967b473cb6d877b12e715b,PMC,Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation,http://dx.doi.org/10.1371/journal.pcbi.1007587,PMC7034926,32040506,CC BY,"Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have been targeted. Identification of host factors on a pan-pathogen level, i.e., genes that are crucial for the replication of a diverse group of pathogens has received relatively little attention, despite the fact that such common host factors would be highly relevant, for instance, for devising broad-spectrum anti-pathogenic drugs. Here, we present a novel two-stage procedure for the identification of host factors involved in the replication of different viruses using a combination of random effects models and Markov random walks on a functional interaction network. We first infer candidate genes by jointly analyzing multiple perturbations screens while at the same time adjusting for high variance inherent in these screens. Subsequently the inferred estimates are spread across a network of functional interactions thereby allowing for the analysis of missing genes in the biological studies, smoothing the effect sizes of previously found host factors, and considering a priori pathway information defined over edges of the network. We applied the procedure to RNAi screening data of four different positive-sense single-stranded RNA viruses, Hepatitis C virus, Chikungunya virus, Dengue virus and Severe acute respiratory syndrome coronavirus, and detected novel host factors, including UBC, PLCG1, and DYRK1B, which are predicted to significantly impact the replication cycles of these viruses. We validated the detected host factors experimentally using pharmacological inhibition and an additional siRNA screen and found that some of the predicted host factors indeed influence the replication of these pathogens.",2020 Feb 10,"['Dirmeier, Simon', 'Dächert, Christopher', 'van Hemert, Martijn', 'Tas, Ali', 'Ogando, Natacha S.', 'van Kuppeveld, Frank', 'Bartenschlager, Ralf', 'Kaderali, Lars', 'Binder, Marco', 'Beerenwinkel, Niko']",PLoS Comput Biol,,,False
9dc436e46261781fe2991baeff4ddc7dd2e96c9b,PMC,Cryo-EM Studies of Virus-Antibody Immune Complexes,http://dx.doi.org/10.1007/s12250-019-00190-5,PMC7035235,31916022,CC BY,"Antibodies play critical roles in neutralizing viral infections and are increasingly used as therapeutic drugs and diagnostic tools. Structural studies on virus-antibody immune complexes are important for better understanding the molecular mechanisms of antibody-mediated neutralization and also provide valuable information for structure-based vaccine design. Cryo-electron microscopy (cryo-EM) has recently matured as a powerful structural technique for studying bio-macromolecular complexes. When combined with X-ray crystallography, cryo-EM provides a routine approach for structurally characterizing the immune complexes formed between icosahedral viruses and their antibodies. In this review, recent advances in the structural understanding of virus-antibody interactions are outlined for whole virions with icosahedral T = pseudo 3 (picornaviruses) and T = 3 (flaviviruses) architectures, focusing on the dynamic nature of viral shells in different functional states. Glycoprotein complexes from pleomorphic enveloped viruses are also discussed as immune complex antigens. Improving our understanding of viral epitope structures using virus-based platforms would provide a fundamental road map for future vaccine development.",2020 Jan 8,"['Li, Na', 'Li, Zhiqiang', 'Fu, Yan', 'Cao, Sheng']",Virol Sin,,,True
e827d65c421e5a5ed761cc56cc2a5f06a3545a82,PMC,Potential benefits of precise corticosteroids therapy for severe 2019-nCoV pneumonia,http://dx.doi.org/10.1038/s41392-020-0127-9,PMC7035340,32133159,CC BY,,2020 Feb 21,"['Zhou, Wei', 'Liu, Yisi', 'Tian, Dongdong', 'Wang, Cheng', 'Wang, Sa', 'Cheng, Jing', 'Hu, Ming', 'Fang, Minghao', 'Gao, Yue']",Signal Transduct Target Ther,,,True
c83b149dc7f5339bd3efa3128d991bb9b802b909,PMC,Management and biosecurity practices on pig farms in the Western Highlands of Cameroon (Central Africa),http://dx.doi.org/10.1002/vms3.211,PMC7036310,31682081,CC BY,"African swine fever (ASF), erysipelas and many other infectious and parasitic diseases have seriously compromised the future of pig industry in the Western Highlands of Cameroon. Since implementation of biosecurity measures (BM) is known to reduce the risk of disease transmission, the objective of this study was to describe the pig farming management system as well as the biosecurity practices on pig farms in the Western Highlands of Cameroon. Therefore, 97 farms were investigated using a face‐to‐face interview‐based questionnaire. Biosecurity practices were divided in three components: isolation, traffic control and sanitation. The results revealed that the majority of farms were extensive (73.22%), farrow‐to‐finish farms (59.79%) and essentially raising crossed‐bred (72.75%). The most practiced BM regarding ‘isolation’ were as follows: maintenance of the minimum distance between farms (56.06%) and dispatching of animals of same age in the same room (97.16%); for ‘traffic control’, the measures included the following: assignment of specific tools and equipment (96.86%) to a specific piggery; concerning ‘sanitation’, daily cleaning (97.06%), as well as using disinfectants (89.13%) were mostly implemented. The measures less implemented for ‘isolation’ included fencing (11.83%), compliance with the all‐in all‐out principle (10.11%), use of specific clothing (6.03%) and quarantine (7.69%); for ‘traffic control’, the less adopted measures comprised visitor hands washed before animal handling (11.65%), respect of linear flow principle (13.52%). Concerning ‘sanitation’, these measures included functional footbath (29.90%), processing of drinking water (27.84%) and cleanout (18.14%). The biosecurity level was low, intermediate and high for 73.71, 21.55 and 4.73% of farms, respectively. This low level suggests that ASF and other diseases are likely to remain endemic. The most important measures of concern and to improve are as follows: not feeding kitchen waste to pigs; keeping other livestock species away from pigs; fencing pig barn; keeping newly arrived animals in quarantine, not exchanging boars; not selling sick animals.",2019 Nov 4,"['Kouam, Marc K.', 'Jacouba, Manjeli', 'Moussala, Junior O.']",Vet Med Sci,,,True
c9306dcd544f76f65824fec6810b03d0c4dfe5a9,PMC,Severe Pulmonary Infection in a 20-Month-Old Female,http://dx.doi.org/10.1155/2020/7301617,PMC7037976,32099701,CC BY,"Community-Acquired Pneumonia (CAP) is a common reason for hospitalization of a pediatric patient. We report a 20-month-old female admitted for suspected CAP. History included a week-long cough, fever, dyspnea, single occurrence of seizure-like activity, and a sick contact. Initial chest X-ray (CXR) showed left lower lobe pneumonia and parapneumonic effusion with a complex left pleural effusion. Ultrasound findings prompted the need for contrast-enhanced computed tomography (CT) of the chest. Contrast-enhanced CT of the chest confirmed a large pleural effusion with major atelectasis and mediastinal shift. The patient was treated with empiric antibiotics, video-assisted thoracoscopic surgical (VATS) decortication of empyema, and chest tube placement. Due to intraoperative complications, the VATS decortication was aborted and patient was transferred to the pediatric intensive care unit (PICU). A thoracentesis with culture failed to isolate a bacterial organism. Dexamethasone was started after repeat CXR showed persistent infiltrate. Subsequent contrast-enhanced CT of the chest showed a large collection of air and persistent consolidation. The patient received repeat VATS decortication and reinsertion of a chest tube. Repeat pleural fluid cultures failed to isolate a bacterial organism. Infectious disease (ID) consult recommended linezolid 140 mg Q8H for 4 weeks. Seven days after second VATS, a respiratory pathogen panel was positive for rhinovirus/enterovirus. With resolution of leukocytosis and clinical improvement, the patient was discharged with the chest tube in place and pediatric surgery outpatient follow-up. After three months, sequalae from both the infection and interventions presented .",2020 Feb 12,"['Mann, Yasmeen', 'Zeller, Paul', 'Carrillo-Kappus, Kristen', 'Victor, Melissa', 'Moore, Mary']",Case Rep Infect Dis,,,True
c11eac2f07f5ad430230013f3eba74ff74a5c8a2,PMC,A Review of Small Molecule Inhibitors and Functional Probes of Human Cathepsin L,http://dx.doi.org/10.3390/molecules25030698,PMC7038230,32041276,CC BY,"Human cathepsin L belongs to the cathepsin family of proteolytic enzymes with primarily an endopeptidase activity. Although its primary functions were originally thought to be only of a housekeeping enzyme that degraded intracellular and endocytosed proteins in lysosome, numerous recent studies suggest that it plays many critical and specific roles in diverse cellular settings. Not surprisingly, the dysregulated function of cathepsin L has manifested itself in several human diseases, making it an attractive target for drug development. Unfortunately, several redundant and isoform-specific functions have recently emerged, adding complexities to the drug discovery process. To address this, a series of chemical biology tools have been developed that helped define cathepsin L biology with exquisite precision in specific cellular contexts. This review elaborates on the recently developed small molecule inhibitors and probes of human cathepsin L, outlining their mechanisms of action, and describing their potential utilities in dissecting unknown function.",2020 Feb 6,"['Dana, Dibyendu', 'Pathak, Sanjai K.']",Molecules,,,True
e9c51ce7b8c15bff3f9cb4de5afc2c862d5544bf,PMC,Screening of Natural Extracts for Inhibitors against Japanese Encephalitis Virus Infection,http://dx.doi.org/10.1128/AAC.02373-19,PMC7038234,31871089,CC BY,"The mosquito-borne Japanese encephalitis virus (JEV) causes serious illness worldwide that is associated with high morbidity and mortality. Currently, there are no effective drugs approved for the treatment of JEV infection. Drug-repurposing screening is an alternative approach to discover potential antiviral agents. In this study, high-content screening (HCS) of a natural extracts library was performed, and two hit FDA-approved Na(+)/K(+)-ATPase inhibitors, ouabain and digoxin, were identified as having robust efficiency against JEV infection with the selectivity indexes over 1,000. The results indicated that ouabain and digoxin blocked the JEV infection at the replication stage by targeting the Na(+)/K(+)-ATPase. Furthermore, it was proven that ouabain significantly reduced the morbidity and mortality caused by JEV in a BALB/c mouse model. This work demonstrated that Na(+)/K(+)-ATPase could serve as the target of treatment of JEV infection, and ouabain has the potential to be developed as an effective anti-JEV drug.",2020 Feb 21,"['Guo, Jiao', 'Jia, Xiaoying', 'Liu, Yang', 'Wang, Shaobo', 'Cao, Junyuan', 'Zhang, Bo', 'Xiao, Gengfu', 'Wang, Wei']",Antimicrob Agents Chemother,,,True
6abb30ae61aa5e41f16a28b9437940d5d76d745b,PMC,"Phase-adjusted estimation of the number of Coronavirus Disease 2019 cases in Wuhan, China",http://dx.doi.org/10.1038/s41421-020-0148-0,PMC7039910,32133152,CC BY,"An outbreak of clusters of viral pneumonia due to a novel coronavirus (2019-nCoV/SARS-CoV-2) happened in Wuhan, Hubei Province in China in December 2019. Since the outbreak, several groups reported estimated R(0) of Coronavirus Disease 2019 (COVID-19) and generated valuable prediction for the early phase of this outbreak. After implementation of strict prevention and control measures in China, new estimation is needed. An infectious disease dynamics SEIR (Susceptible, Exposed, Infectious, and Removed) model was applied to estimate the epidemic trend in Wuhan, China under two assumptions of R(t). In the first assumption, R(t) was assumed to maintain over 1. The estimated number of infections would continue to increase throughout February without any indication of dropping with R(t) = 1.9, 2.6, or 3.1. The number of infections would reach 11,044, 70,258, and 227,989, respectively, by 29 February 2020. In the second assumption, R(t) was assumed to gradually decrease at different phases from high level of transmission (R(t) = 3.1, 2.6, and 1.9) to below 1 (R(t) = 0.9 or 0.5) owing to increasingly implemented public health intervention. Several phases were divided by the dates when various levels of prevention and control measures were taken in effect in Wuhan. The estimated number of infections would reach the peak in late February, which is 58,077–84,520 or 55,869–81,393. Whether or not the peak of the number of infections would occur in February 2020 may be an important index for evaluating the sufficiency of the current measures taken in China. Regardless of the occurrence of the peak, the currently strict measures in Wuhan should be continuously implemented and necessary strict public health measures should be applied in other locations in China with high number of COVID-19 cases, in order to reduce R(t) to an ideal level and control the infection.",2020 Feb 24,"['Wang, Huwen', 'Wang, Zezhou', 'Dong, Yinqiao', 'Chang, Ruijie', 'Xu, Chen', 'Yu, Xiaoyue', 'Zhang, Shuxian', 'Tsamlag, Lhakpa', 'Shang, Meili', 'Huang, Jinyan', 'Wang, Ying', 'Xu, Gang', 'Shen, Tian', 'Zhang, Xinxin', 'Cai, Yong']",Cell Discov,,,True
7c567cd1c7c9e6cb5b4dcb5e4e62316cea63e593,PMC,High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa,http://dx.doi.org/10.1038/s41368-020-0074-x,PMC7039956,32094336,CC BY,"It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. To investigate the potential route of 2019-nCov infection on the mucosa of oral cavity, bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas (TCGA) and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression (FANTOM5 CAGE) dataset were collected. RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA and 14 organ types with normal tissues from FANTOM5 CAGE were analyzed in order to explore and validate the expression of ACE2 on the mucosa of oral cavity. Further, single-cell transcriptomes from an independent data generated in-house were used to identify and confirm the ACE2-expressing cell composition and proportion in oral cavity. The results demonstrated that the ACE2 expressed on the mucosa of oral cavity. Interestingly, this receptor was highly enriched in epithelial cells of tongue. Preliminarily, those findings have explained the basic mechanism that the oral cavity is a potentially high risk for 2019-nCoV infectious susceptibility and provided a piece of evidence for the future prevention strategy in dental clinical practice as well as daily life.",2020 Feb 24,"['Xu, Hao', 'Zhong, Liang', 'Deng, Jiaxin', 'Peng, Jiakuan', 'Dan, Hongxia', 'Zeng, Xin', 'Li, Taiwen', 'Chen, Qianming']",Int J Oral Sci,,,True
53eccda7977a31e3d0f565c884da036b1e85438e,PMC,Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations,http://dx.doi.org/10.1038/s41421-020-0147-1,PMC7040011,32133153,CC BY,,2020 Feb 24,"['Cao, Yanan', 'Li, Lin', 'Feng, Zhimin', 'Wan, Shengqing', 'Huang, Peide', 'Sun, Xiaohui', 'Wen, Fang', 'Huang, Xuanlin', 'Ning, Guang', 'Wang, Weiqing']",Cell Discov,,,True
372caa549b07492de5fd7064e9cadc62bef0f478,PMC,NLRP3 Inflammasome—A Key Player in Antiviral Responses,http://dx.doi.org/10.3389/fimmu.2020.00211,PMC7040071,32133002,CC BY,"The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is an oligomeric complex comprised of the NOD-like receptor NLRP3, the adaptor ASC, and caspase-1. This complex is crucial to the host's defense against microbes as it promotes IL-1β and IL-18 secretion and induces pyroptosis. NLRP3 recognizes variety of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) generated during viral replication that triggers the NLRP3 inflammasome-dependent antiviral immune responses and facilitates viral eradication. Meanwhile, several viruses have evolved elaborate strategies to evade the immune system by targeting the NLRP3 inflammasome. In this review, we will focus on the crosstalk between the NLRP3 inflammasome and viruses, provide an overview of viral infection-induced NLRP3 inflammasome activation, and the immune escape strategies of viruses through their modulation of the NLRP3 inflammasome activity.",2020 Feb 18,"['Zhao, Chunyuan', 'Zhao, Wei']",Front Immunol,,,True
b6c38211730ff7826aa6a52aff9e3be848f8e738,PMC,Expression Pattern Analysis of Antiviral Genes and Inflammatory Cytokines in PEDV-Infected Porcine Intestinal Epithelial Cells,http://dx.doi.org/10.3389/fvets.2020.00075,PMC7040077,32133381,CC BY,"Porcine diarrhea disease in newborn and suckling piglets due to infection with porcine epidemic diarrhea virus (PEDV) is a leading cause of economic loss in the pig industry globally. In this study, we investigated the molecular mechanism of the host innate immune response to PEDV infection. The expression dynamics of antiviral genes (e.g., RIG-1, PKR, OAS1, Mx1, and Mx2) and inflammatory cytokines (e.g., IFN-α, IFN-β, TNF-α, IL-6, IL-8, and IL-12) in porcine small intestinal epithelial (IPEC-J2) cells were analyzed following PEDV stimulation. The results showed that the expression of antiviral genes (e.g., PKR, OAS1, and Mx2) and inflammatory cytokines (e.g., IFN-α and TNF-α) were significantly reduced within 0–4 h post-infection (P < 0.05). However, all antiviral genes and inflammatory cytokines were up-regulated from 12 to 24 h (P < 0.05), and cytopathic changes were observed during this time. The expression of RIG-1, PKR, OAS1, Mx1, and Mx2 were significantly and positively correlated to each other during the entire infection (P < 0.01). The results suggested that the RIG-1, PKR, OAS1, Mx1, and Mx2 genes may play an important role in PEDV infection in piglets. Initially, PEDV displayed cellular invasion by inhibiting IFN-α transcription and interfering with the antiviral function of PKR, OAS1, and Mx2, ultimately induced an intense inflammatory response. The relationship between antiviral genes and inflammatory cytokines with PEDV infection at the cellular level provides a reference for studying the mechanism of resistance to PEDV infection in piglets.",2020 Feb 18,"['Wang, Shiqin', 'Wu, Jiayun', 'Wang, Fang', 'Wang, Haifei', 'Wu, Zhengchang', 'Wu, Shenglong', 'Bao, Wenbin']",Front Vet Sci,,,True
3fd4c59ae94e2ecc44c0c40d678dd18e31ddb7c7,PMC,Human matriptase/ST 14 proteolytically cleaves H7N9 hemagglutinin and facilitates the activation of influenza A/Shanghai/2/2013 virus in cell culture,http://dx.doi.org/10.1111/irv.12707,PMC7040964,31820577,CC BY,"BACKGROUND: Influenza is a zoonotic disease that infects millions of people each year resulting in hundreds of thousands of deaths, and in turn devastating pandemics. Influenza is caused by influenza viruses, including influenza A virus (IAV). There are many subtypes of IAV but only a few seem to be able to adapt to humans and to cause disease. In 2013, an H7N9 IAV subtype emerged in China that does not cause clinical symptoms in its chicken host but leads to severe infections when transmitted into humans. Since 2013, there have been six epidemic waves of H7N9 with 1567 laboratory‐confirmed human infections and 615 deaths. Pathogenicity of IAV is complex, but a crucial feature contributing to virulence is the activation of the hemagglutinin (HA) fusion protein by host proteases that triggers membrane fusion and leads to subsequent virus propagation. METHODS: 293T, VERO, and MDCK cells were used to conduct Western blot analysis, immunofluorescence assays, and pseudoparticle and live virus infections, and to evaluate H7N9 HA cleavage‐activation. RESULTS/CONCLUSIONS: We show that human matriptase/ST 14 is able to cleave H7N9 HA. Cleavage of H7N9 HA expressed in cell culture results in fusogenic HA and syncytia formation. In infection studies with viral pseudoparticles carrying matriptase/ST 14‐activated H7N9 HA, we observed a high infectivity of cells. Finally, human matriptase/ST 14 also activated H7N9 live virus which resulted in high infectivity. Our data demonstrate that human matriptase/ST 14 is a likely candidate protease to promote H7N9 infections in humans.",2020 Mar 9,"['Whittaker, Gary R.', 'Straus, Marco R.']",Influenza Other Respir Viruses,,,True
0293ec2b1cf8097392297cffd06854d2f37348f4,PMC,"Rapid detection of respiratory organisms with FilmArray respiratory panel and its impact on clinical decisions in Shanghai, China, 2016‐2018",http://dx.doi.org/10.1111/irv.12701,PMC7040966,31786832,CC BY,"BACKGROUND: In this study, we evaluated the diagnostic potential and clinical impact of an automated multiplex PCR platform (the FilmArray Respiratory Panel; FA‐RP), specially designed for pathogen detection in respiratory tract infections in adults with unexplained pneumonia (UP). METHODS: A total of 112 UP patients in Shanghai, China, were enrolled prospectively and assessed using the FA‐RP from October 2016 to March 2018. We examined the test results and their influence on clinical decisions. Furthermore, as a control group, we retrospectively obtained the clinical data of 70 UP patients between October 2014 and March 2016 (before the FA‐RP was available). The two patient groups were compared with respect to factors, including general antimicrobial use and defined daily dose (DDD) numbers. RESULTS: Between October 2016 and March 2018, the positive rate obtained using FA‐RP for UP was 76.8%. The primary pathogens in adults with UP were Influenza A/B (47.3%, 53/112). Compared with the patients before FA‐RP was available, patients who underwent FA‐RP testing had higher rates of antiviral drug use and antibiotic de‐escalation during clinical treatment. FA‐RP significantly decreased the total DDDs of antibiotic or antifungal drugs DDDs by 7 days after admission (10.6 ± 2.5 vs 14.1 ± 8.8, P < .01). CONCLUSIONS: The FA‐RP is a rapid and sensitive nucleic acid amplification test method for UP diagnosis in adults. The application of FA‐RP may lead to a more accurately targeted antimicrobial treatment and reduced use of antibiotic/antifungal drugs.",2020 Mar 1,"['Qian, Yiyi', 'Ai, Jingwen', 'Wu, Jing', 'Yu, Shenglei', 'Cui, Peng', 'Gao, Yan', 'Jin, Jialin', 'Weng, Xinhua', 'Zhang, Wenhong']",Influenza Other Respir Viruses,,,True
98aca16ac6513c25abcf54bc1dbe7b6fe65e9c49,PMC,"Comparison of suspension MDCK cells, adherent MDCK cells, and LLC‐MK2 cells for selective isolation of influenza viruses to be used as vaccine seeds",http://dx.doi.org/10.1111/irv.12694,PMC7040968,31651085,CC BY,"BACKGROUND: Cell‐based influenza vaccines can solve the problem of the frequent occurrence of egg adaptation–associated antigenic changes observed in egg‐based vaccines. Seed viruses for cell‐based vaccines can be prepared from clinical specimens by cell culture; however, clinical samples risk harboring respiratory viruses other than influenza virus. Therefore, it is necessary to investigate the patterns of co‐infection in clinical samples and explore whether cell culture technology can selectively propagate influenza viruses from samples containing other respiratory viruses. METHODS: A total of 341 clinical specimens were collected from patients with influenza or influenza‐like illness and analyzed by ResPlex II assay to detect 18 respiratory viruses. The patterns of co‐infection were statistically analyzed with Fisher's exact test. The samples with double or triple infections were passaged in suspension MDCK cells (MDCK‐S), adherent MDCK cells (MDCK‐A), and LLC‐MK2D cells. Cell‐passaged samples were analyzed by ResPlex II assay again to investigate whether each cell line could amplify influenza viruses and eliminate other respiratory viruses. RESULTS: Double infections were detected in 8.5% and triple infections in 0.9% of the collected clinical specimens. We identified four pairs of viruses with significant correlation. For all samples with double and triple infection, MDCK‐S and MDCK‐A could selectively propagate influenza viruses, while eliminating all contaminating viruses. In contrast, LLC‐MK2D showed lower isolation efficiency for influenza virus and higher isolation efficiency for coxsackievirus/echovirus than MDCK‐S and MDCK‐A. CONCLUSIONS: Both MDCK‐S and MDCK‐A are considered suitable for the preparation of influenza vaccine seed viruses without adventitious agents or egg‐adaptation mutations.",2020 Mar 25,"['Harada, Yuichi', 'Takahashi, Hitoshi', 'Trusheim, Heidi', 'Roth, Bernhard', 'Mizuta, Katsumi', 'Hirata‐Saito, Asumi', 'Ogane, Teruko', 'Odagiri, Takato', 'Tashiro, Masato', 'Yamamoto, Norio']",Influenza Other Respir Viruses,,,True
6a8d67876f9d695b2ad3251846bb303a9cc46ba1,PMC,"Strengthening timely detection and reporting of unusual respiratory events from health facilities in Yaoundé, Cameroon",http://dx.doi.org/10.1111/irv.12684,PMC7040971,31923349,CC BY,"BACKGROUND: The International Health Regulations state that early detection and immediate reporting of unusual health events is important for early warning and response systems. OBJECTIVE: To describe a pilot surveillance program established in health facilities in Yaoundé, Cameroon in 2017 which aimed to enable detection and reporting of public health events. METHODS: Cameroon’s Ministry of Health, in partnership with the US Centers for Disease Control and Prevention, Cameroon Pasteur Center, and National Public Health Laboratory, implemented event‐based surveillance (EBS) in nine Yaoundé health facilities. Four signals were defined that could indicate possible public health events, and a reporting, triage, and verification system was established among partner organizations. A pre‐defined laboratory algorithm was defined, and a series of workshops trained health facilities, laboratory, and public health staff for surveillance implementation. RESULTS: From May 2017 to January 2018, 30 signals were detected, corresponding to 15 unusual respiratory events. All health facilities reported a signal at least once, and more than three‐quarters of health facilities reported ≥2 times. Among specimens tested, the pathogens detected included Klebsiella pneumoniae, Moraxella catarrhalis, Streptococcus pneumoniae, Haemophilus influenza, Staphylococcus aureus, Pneumocystis jiroveci, influenza A (H1N1) virus, rhinovirus, and adenovirus. CONCLUSIONS: The events detected in this pilot were caused by routine respiratory bacteria and viruses, and no novel influenza viruses or other emerging respiratory threats were identified. The surveillance system, however, strengthened relationships and communication linkages between health facilities and public health authorities. Astute clinicians can play a critical role in early detection and EBS is one approach that may enable reporting of emerging outbreaks and public health events.",2020 Mar 10,"['Alroy, Karen A.', 'Gwom, Luc Christian', 'Ndongo, Chanceline Bilounga', 'Kenmoe, Sebastien', 'Monamele, Gwladys', 'Clara, Alexey', 'Whitaker, Brett', 'Manga, Henri', 'Tayimetha, Carolle Yanique', 'Tseuko, Dorine', 'Etogo, Bienvenu', 'Pasi, Omer', 'Etoundi, Alain Georges', 'Seukap, Elise', 'Njouom, Richard', 'Balajee, Arunmozhi']",Influenza Other Respir Viruses,,,True
1e0851ed44e0459ff83448af23b81560a41ede72,PMC,Late viral or bacterial respiratory infections in lung transplanted patients: impact on respiratory function,http://dx.doi.org/10.1186/s12879-020-4877-3,PMC7041086,32093612,CC BY,"BACKGROUND: Respiratory infections are a major threat for lung recipients. We aimed to compare with a monocentric study the impact of late viral and bacterial respiratory infections on the graft function. METHODS: Patients, who survived 6 months or more following lung transplantation that took place between 2009 and 2014, were classified into three groups: a viral infection group (VIG) (without any respiratory bacteria), a bacterial infection group (BIG) (with or without any respiratory viruses), and a control group (CG) (no documented infection). Chronic lung allograft dysfunction (CLAD) and acute rejection were analysed 6 months after the inclusion in the study. RESULTS: Among 99 included lung recipients, 57 (58%) had at least one positive virological respiratory sample during the study period. Patients were classified as follows: 38 in the VIG, 25 in the BIG (among which 19 co-infections with a virus) and 36 in the CG. The BIG presented a higher initial deterioration in lung function (p = 0.05) than the VIG. But 6 months after the infection, only the VIG presented a median decrease of forced expiratory volume in 1 s; − 35 mL (IQR; − 340; + 80) in the VIG, + 140 mL (+ 60;+ 330) in the BIG and + 10 (− 84;+ 160) in the CG, p < 0.01. Acute rejection was more frequent in the VIG (n = 12 (32%)), than the BIG (n = 6 (24%)) and CG (n = 3 (8%)), p < 0.05, despite presenting no more CLAD (p = 0.21). CONCLUSIONS: Despite a less severe initial presentation, single viral respiratory infections seem to lead to a greater deterioration in lung function, and to more acute rejection, than bacterial infections.",2020 Feb 24,"['Dubert, Marie', 'Visseaux, Benoit', 'Birgy, André', 'Mordant, Pierre', 'Metivier, Anne-Cécile', 'Dauriat, Gaelle', 'Fidouh, Nadhira', 'Yazdanpanah, Yazdan', 'Grall, Nathalie', 'Castier, Yves', 'Mal, Hervé', 'Thabut, Gabriel', 'Lescure, François-Xavier']",BMC Infect Dis,,,True
44a5bfa3f7ab0f7df199e81440995ab24b8e1c58,PMC,"Overnutrition in Infants Is Associated With High Level of Leptin, Viral Coinfection and Increased Severity of Respiratory Infections: A Cross-Sectional Study",http://dx.doi.org/10.3389/fped.2020.00044,PMC7041426,32133330,CC BY,"Objective: To investigate the relationship of overnutrition (obese and overweight) with severity of illness in children hospitalized with acute lower respiratory infections (ALRIs), frequency of viral coinfections and leptin levels. Methods: We studied 124 children <2 years old that were hospitalized for ALRI. Nutritional status was calculated by z-scores according to weight-for-age z-scores, length or height-for-age z-scores, and weight-for-height z-scores. Nasopharyngeal aspirates (NPAs) were obtained and viral respiratory pathogens were identified using reverse transcription polymerase chain reactions (RT-PCR). Respiratory syncytial virus (RSV) load was assessed using quantitative RT-PCR. NPA and plasma leptin level were measured. Clinical data and nutritional status were recorded, and patients were followed up until hospital discharge. Viral coinfection was defined as the presence of two or more viruses detected in the same respiratory sample. Severity of illness was determined by length of hospitalization and duration of oxygen therapy. Results: Children with overnutrition showed a greater frequency of viral coinfection than those with normal weight (71% obese vs. 37% normal weight p = 0.013; 68% overweight vs. 37% normal weight p = 0.004). A lower RSV load was found in obese (5.91 log(10) copies/mL) and overweight children (6.49 log(10) copies/mL) compared to normal weight children (8.06 log(10) copies/mL; p = 0.021 in both cases). In multivariate analysis, obese, and overweight infants <6 months old were associated with longer hospital stays (RR = 1.68; CI: 1.30–2.15 and obese: RR = 1.68; CI: 1.01–2.71, respectively) as well as a greater duration of oxygen therapy (RR = 1.80; IC: 1.41–2.29 and obese: RR = 1.91; CI: 1.15–3.15, respectively). Obese children <6 months showed higher plasma leptin level than normal weight children (7.58 vs. 5.12 ng/μl; p <0.046). Conclusions: In infants younger than 6 months, overnutrition condition was related to increased severity of infections and high plasma leptin level. Also, children with overnutrition showed a greater frequency of viral coinfection and low RSV viral load compared to normal weights children. These findings further contribute to the already existent evidence supporting the importance of overnutrition prevention in pediatric populations.",2020 Feb 18,"['Arias-Bravo, Guisselle', 'Valderrama, Gustavo', 'Inostroza, Jaime', 'Reyes-Farías, Marjorie', 'Garcia-Diaz, Diego F.', 'Zorondo-Rodríguez, Francisco', 'Fuenzalida, Loreto F.']",Front Pediatr,,,True
db3f6cc774e724f7e9be22d7e76d489a1c131a46,PMC,Spontaneous lung pathology in a captive common marmoset colony (Callithrix jacchus),http://dx.doi.org/10.5194/pb-4-17-2017,PMC7041528,32110688,CC BY,"Data on spontaneous pathology are substantially scarce for common marmosets, compared to other laboratory animals, but is essential for the interpretation of histological findings in the context of toxicological and experimental studies. Especially if common marmosets are used as experimental animals in respiratory research, detailed knowledge on the spectrum, occurrence, and incidence of spontaneous histopathological pulmonary lesions in this non-human primate species is required. In this study, lung tissue of 638 common marmosets from the marmoset colony of the German Primate Center was examined histologically. The analysis revealed a high incidence of predominantly mild and multifocal interstitial pneumonia (32.99 %) of unknown etiology in most cases. Only few marmosets exhibited lobar pneumonia (1.41 %) and bronchopneumonia (0.94), which were mainly caused by bacterial pathogens such as Bordetella bronchiseptica and Klebsiella pneumoniae. Lung immaturity and atelectasis were common histological findings in newborn marmosets. Typical background lesions included anthracosis (8.15 %), hemosiderosis (1.72 %), extramedullary hematopoiesis (11.6 %), mineralization (10.97 %), and inflammatory cell foci (10.34 %). In addition, three cases of pulmonary arteriopathy (0.47 %) and 1 case of foreign-body granuloma (0.16 %) were detected in the marmoset study cohort. The high prevalence of circulatory disturbances (congestion, edema, hemorrhage) and changes in air content (secondary atelectasis, alveolar emphysema) could partly be explained by euthanasia-related artifacts or agonal changes. The present study provides a comprehensive overview of the range and incidence of spontaneous pulmonary histopathology in common marmosets, serving as valuable reference data for the interpretation of lung lesions in toxicological and experimental marmoset studies.",2017 Mar 1,"['Bleyer, Martina', 'Kunze, Marius', 'Gruber-Dujardin, Eva', 'Mätz-Rensing, Kerstin']",Primate Biol,,,True
3bb907cbe9deee5e9585de1c0c7f04d15a82fafd,PMC,Plans and prospects for the 2020s: Beyond peak health?,http://dx.doi.org/10.1371/journal.pmed.1003075,PMC7041788,32097415,CC BY,The PLOS Medicine editors discuss prospects for health and development in the coming decade.,2020 Feb 25,,PLoS Med,,,True
d45434768bff438c55a2ec36d9821e40fe7ddc7d,PMC,Discovery of antitumor lectins from rainforest tree root transcriptomes,http://dx.doi.org/10.1371/journal.pone.0229467,PMC7041804,32097449,CC BY,"Glycans are multi-branched sugars that are displayed from lipids and proteins. Through their diverse polysaccharide structures they can potentiate a myriad of cellular signaling pathways involved in development, growth, immuno-communication and survival. Not surprisingly, disruption of glycan synthesis is fundamental to various human diseases; including cancer, where aberrant glycosylation drives malignancy. Here, we report the discovery of a novel mannose-binding lectin, ML6, which selectively recognizes and binds to these irregular tumor-specific glycans to elicit potent and rapid cancer cell death. This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence. Remarkably, ML6 displays antitumor activity that is >10(5) times more potent than standard chemotherapeutics, while being almost completely inactive towards non-transformed, healthy cells. This activity, in combination with results from glycan binding studies, suggests ML6 differentiates healthy and malignant cells by exploiting divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors. Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies. Further, understanding how nature evolves proteins, like ML6, to combat the changing defenses of competing microorganisms may allow for fundamental advances in the way we approach combinatorial therapies to fight therapeutic resistance in cancer.",2020 Feb 25,"['Lawanprasert, Atip', 'Guinan, Caitlin A.', 'Langford, Erica A.', 'Hawkins, Carly E.', 'Sloand, Janna N.', 'Fescemyer, Howard W.', 'Aronson, Matthew R.', 'Halle, Jacob A.', 'Marden, James H.', 'Medina, Scott H.']",PLoS One,,,True
b653e8b305251ed9a72601e909d232286409cb73,PMC,Natural selection supports escape from concerted evolution of a recently duplicated CEACAM1 paralog in the ruminant CEA gene family,http://dx.doi.org/10.1038/s41598-020-60425-4,PMC7042247,32099040,CC BY,"Concerted evolution is often observed in multigene families such as the CEA gene family. As a result, sequence similarity of paralogous genes is significantly higher than expected from their evolutionary distance. Gene conversion, a “copy paste” DNA repair mechanism that transfers sequences from one gene to another and homologous recombination are drivers of concerted evolution. Nevertheless, some gene family members escape concerted evolution and acquire sufficient sequence differences that orthologous genes can be assigned in descendant species. Reasons why some gene family members can escape while others are captured by concerted evolution are poorly understood. By analyzing the entire CEA gene family in cattle (Bos taurus) we identified a member (CEACAM32) that was created by gene duplication and cooption of a unique transmembrane domain exon in the most recent ancestor of ruminants. CEACAM32 shows a unique, testis-specific expression pattern. Phylogenetic analysis indicated that CEACAM32 is not involved in concerted evolution of CEACAM1 paralogs in ruminants. However, analysis of gene conversion events revealed that CEACAM32 is subject to gene conversion but remarkably, these events are found in the leader exon and intron sequences but not in exons coding for the Ig-like domains. These findings suggest that natural selection hinders gene conversion affecting protein sequences of the mature protein and thereby support escape of CEACAM32 from concerted evolution.",2020 Feb 25,"['Hänske, Jana', 'Hammacher, Tim', 'Grenkowitz, Franziska', 'Mansfeld, Martin', 'Dau, Tung Huy', 'Maksimov, Pavlo', 'Friedrich, Christin', 'Zimmermann, Wolfgang', 'Kammerer, Robert']",Sci Rep,,,False
2e45e30b65fd34a5727e967dda22436bffc2b57e,PMC,Natural selection supports escape from concerted evolution of a recently duplicated CEACAM1 paralog in the ruminant CEA gene family,http://dx.doi.org/10.1038/s41598-020-60425-4,PMC7042247,32099040,CC BY,"Concerted evolution is often observed in multigene families such as the CEA gene family. As a result, sequence similarity of paralogous genes is significantly higher than expected from their evolutionary distance. Gene conversion, a “copy paste” DNA repair mechanism that transfers sequences from one gene to another and homologous recombination are drivers of concerted evolution. Nevertheless, some gene family members escape concerted evolution and acquire sufficient sequence differences that orthologous genes can be assigned in descendant species. Reasons why some gene family members can escape while others are captured by concerted evolution are poorly understood. By analyzing the entire CEA gene family in cattle (Bos taurus) we identified a member (CEACAM32) that was created by gene duplication and cooption of a unique transmembrane domain exon in the most recent ancestor of ruminants. CEACAM32 shows a unique, testis-specific expression pattern. Phylogenetic analysis indicated that CEACAM32 is not involved in concerted evolution of CEACAM1 paralogs in ruminants. However, analysis of gene conversion events revealed that CEACAM32 is subject to gene conversion but remarkably, these events are found in the leader exon and intron sequences but not in exons coding for the Ig-like domains. These findings suggest that natural selection hinders gene conversion affecting protein sequences of the mature protein and thereby support escape of CEACAM32 from concerted evolution.",2020 Feb 25,"['Hänske, Jana', 'Hammacher, Tim', 'Grenkowitz, Franziska', 'Mansfeld, Martin', 'Dau, Tung Huy', 'Maksimov, Pavlo', 'Friedrich, Christin', 'Zimmermann, Wolfgang', 'Kammerer, Robert']",Sci Rep,,,True
c4943b5cc55140da6a5bbf9e5ecb5d6729f0728d,PMC,A Mini-Review on the Epidemiology of Canine Parvovirus in China,http://dx.doi.org/10.3389/fvets.2020.00005,PMC7044151,,CC BY,"Canine viral diarrhea is a severe disease in dogs worldwide. The role of canine parvovirus (CPV) in canine viral diarrhea is a common health problem in dogs, attracting major concern from veterinarians and dog owners across China. In this mini-review, we summarize the CPV epidemiology in China, including its origin, prevalence, coinfection, and the genetic evolution of the virus. The review reveals the correlation between CPV-2 infection and seasonality, a dog's age/gender/breed/vaccination; that CPV-2 is the main causative agent of canine diarrhea in Northeast China and that coinfection with other pathogens is a common occurrence; the predominant CPV epidemic strains were the new CPV-2a, and CPV-2c has shown significant growth trends since 2010. This mini-review will provide valuable information for CPV infections across China and other countries.",2020 Feb 20,"['Qi, Shanshan', 'Zhao, Jianjun', 'Guo, Donghua', 'Sun, Dongbo']",Front Vet Sci,,,True
29e29db383421f822834a63f2722bfceff5a0625,PMC,B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction,http://dx.doi.org/10.1038/s41467-020-14867-z,PMC7044196,32103002,CC BY,"Angiotensin-converting enzyme 2 (ACE2) is critically involved in cardiovascular physiology and pathology, and is currently clinically evaluated to treat acute lung failure. Here we show that the B38-CAP, a carboxypeptidase derived from Paenibacillus sp. B38, is an ACE2-like enzyme to decrease angiotensin II levels in mice. In protein 3D structure analysis, B38-CAP homolog shares structural similarity to mammalian ACE2 with low sequence identity. In vitro, recombinant B38-CAP protein catalyzed the conversion of angiotensin II to angiotensin 1–7, as well as other known ACE2 target peptides. Treatment with B38-CAP suppressed angiotensin II-induced hypertension, cardiac hypertrophy, and fibrosis in mice. Moreover, B38-CAP inhibited pressure overload-induced pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction in mice. Our data identify the bacterial B38-CAP as an ACE2-like carboxypeptidase, indicating that evolution has shaped a bacterial carboxypeptidase to a human ACE2-like enzyme. Bacterial engineering could be utilized to design improved protein drugs for hypertension and heart failure.",2020 Feb 26,"['Minato, Takafumi', 'Nirasawa, Satoru', 'Sato, Teruki', 'Yamaguchi, Tomokazu', 'Hoshizaki, Midori', 'Inagaki, Tadakatsu', 'Nakahara, Kazuhiko', 'Yoshihashi, Tadashi', 'Ozawa, Ryo', 'Yokota, Saki', 'Natsui, Miyuki', 'Koyota, Souichi', 'Yoshiya, Taku', 'Yoshizawa-Kumagaye, Kumiko', 'Motoyama, Satoru', 'Gotoh, Takeshi', 'Nakaoka, Yoshikazu', 'Penninger, Josef M.', 'Watanabe, Hiroyuki', 'Imai, Yumiko', 'Takahashi, Saori', 'Kuba, Keiji']",Nat Commun,,,False
f93d4e67a3ec41e2f304b0af5955d84b548ab53c,PMC,B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction,http://dx.doi.org/10.1038/s41467-020-14867-z,PMC7044196,32103002,CC BY,"Angiotensin-converting enzyme 2 (ACE2) is critically involved in cardiovascular physiology and pathology, and is currently clinically evaluated to treat acute lung failure. Here we show that the B38-CAP, a carboxypeptidase derived from Paenibacillus sp. B38, is an ACE2-like enzyme to decrease angiotensin II levels in mice. In protein 3D structure analysis, B38-CAP homolog shares structural similarity to mammalian ACE2 with low sequence identity. In vitro, recombinant B38-CAP protein catalyzed the conversion of angiotensin II to angiotensin 1–7, as well as other known ACE2 target peptides. Treatment with B38-CAP suppressed angiotensin II-induced hypertension, cardiac hypertrophy, and fibrosis in mice. Moreover, B38-CAP inhibited pressure overload-induced pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction in mice. Our data identify the bacterial B38-CAP as an ACE2-like carboxypeptidase, indicating that evolution has shaped a bacterial carboxypeptidase to a human ACE2-like enzyme. Bacterial engineering could be utilized to design improved protein drugs for hypertension and heart failure.",2020 Feb 26,"['Minato, Takafumi', 'Nirasawa, Satoru', 'Sato, Teruki', 'Yamaguchi, Tomokazu', 'Hoshizaki, Midori', 'Inagaki, Tadakatsu', 'Nakahara, Kazuhiko', 'Yoshihashi, Tadashi', 'Ozawa, Ryo', 'Yokota, Saki', 'Natsui, Miyuki', 'Koyota, Souichi', 'Yoshiya, Taku', 'Yoshizawa-Kumagaye, Kumiko', 'Motoyama, Satoru', 'Gotoh, Takeshi', 'Nakaoka, Yoshikazu', 'Penninger, Josef M.', 'Watanabe, Hiroyuki', 'Imai, Yumiko', 'Takahashi, Saori', 'Kuba, Keiji']",Nat Commun,,,False
ffbb656b0fcfaa8c5853f64b9cc2bbc37f5034b5,PMC,B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction,http://dx.doi.org/10.1038/s41467-020-14867-z,PMC7044196,32103002,CC BY,"Angiotensin-converting enzyme 2 (ACE2) is critically involved in cardiovascular physiology and pathology, and is currently clinically evaluated to treat acute lung failure. Here we show that the B38-CAP, a carboxypeptidase derived from Paenibacillus sp. B38, is an ACE2-like enzyme to decrease angiotensin II levels in mice. In protein 3D structure analysis, B38-CAP homolog shares structural similarity to mammalian ACE2 with low sequence identity. In vitro, recombinant B38-CAP protein catalyzed the conversion of angiotensin II to angiotensin 1–7, as well as other known ACE2 target peptides. Treatment with B38-CAP suppressed angiotensin II-induced hypertension, cardiac hypertrophy, and fibrosis in mice. Moreover, B38-CAP inhibited pressure overload-induced pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction in mice. Our data identify the bacterial B38-CAP as an ACE2-like carboxypeptidase, indicating that evolution has shaped a bacterial carboxypeptidase to a human ACE2-like enzyme. Bacterial engineering could be utilized to design improved protein drugs for hypertension and heart failure.",2020 Feb 26,"['Minato, Takafumi', 'Nirasawa, Satoru', 'Sato, Teruki', 'Yamaguchi, Tomokazu', 'Hoshizaki, Midori', 'Inagaki, Tadakatsu', 'Nakahara, Kazuhiko', 'Yoshihashi, Tadashi', 'Ozawa, Ryo', 'Yokota, Saki', 'Natsui, Miyuki', 'Koyota, Souichi', 'Yoshiya, Taku', 'Yoshizawa-Kumagaye, Kumiko', 'Motoyama, Satoru', 'Gotoh, Takeshi', 'Nakaoka, Yoshikazu', 'Penninger, Josef M.', 'Watanabe, Hiroyuki', 'Imai, Yumiko', 'Takahashi, Saori', 'Kuba, Keiji']",Nat Commun,,,False
95f3513f4173df6761cba6c75b1b518b66ce5502,PMC,B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction,http://dx.doi.org/10.1038/s41467-020-14867-z,PMC7044196,32103002,CC BY,"Angiotensin-converting enzyme 2 (ACE2) is critically involved in cardiovascular physiology and pathology, and is currently clinically evaluated to treat acute lung failure. Here we show that the B38-CAP, a carboxypeptidase derived from Paenibacillus sp. B38, is an ACE2-like enzyme to decrease angiotensin II levels in mice. In protein 3D structure analysis, B38-CAP homolog shares structural similarity to mammalian ACE2 with low sequence identity. In vitro, recombinant B38-CAP protein catalyzed the conversion of angiotensin II to angiotensin 1–7, as well as other known ACE2 target peptides. Treatment with B38-CAP suppressed angiotensin II-induced hypertension, cardiac hypertrophy, and fibrosis in mice. Moreover, B38-CAP inhibited pressure overload-induced pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction in mice. Our data identify the bacterial B38-CAP as an ACE2-like carboxypeptidase, indicating that evolution has shaped a bacterial carboxypeptidase to a human ACE2-like enzyme. Bacterial engineering could be utilized to design improved protein drugs for hypertension and heart failure.",2020 Feb 26,"['Minato, Takafumi', 'Nirasawa, Satoru', 'Sato, Teruki', 'Yamaguchi, Tomokazu', 'Hoshizaki, Midori', 'Inagaki, Tadakatsu', 'Nakahara, Kazuhiko', 'Yoshihashi, Tadashi', 'Ozawa, Ryo', 'Yokota, Saki', 'Natsui, Miyuki', 'Koyota, Souichi', 'Yoshiya, Taku', 'Yoshizawa-Kumagaye, Kumiko', 'Motoyama, Satoru', 'Gotoh, Takeshi', 'Nakaoka, Yoshikazu', 'Penninger, Josef M.', 'Watanabe, Hiroyuki', 'Imai, Yumiko', 'Takahashi, Saori', 'Kuba, Keiji']",Nat Commun,,,True
3078165241b24fed34596efa9f563661f1caa00c,PMC,MiR-10a-5p-Mediated Syndecan 1 Suppression Restricts Porcine Hemagglutinating Encephalomyelitis Virus Replication,http://dx.doi.org/10.3389/fmicb.2020.00105,PMC7044266,,CC BY,"Porcine hemagglutinating encephalomyelitis virus (PHEV) is a single-stranded RNA coronavirus that causes nervous dysfunction in the infected hosts and leads to widespread alterations in the host transcriptome by modulating specific microRNA (miRNA) levels. MiRNAs contribute to RNA virus pathogenesis by promoting antiviral immune response, enhancing viral replication, or altering miRNA-mediated host gene regulation. Thus, exploration of the virus–miRNA interactions occurring in PHEV-infected host may lead to the identification of novel mechanisms combating the virus life cycle or pathogenesis. Here, we discovered that the expression of miR-10a-5p was constitutively up-regulated by PHEV in both the N2a cells in vitro and mice brain in vivo. Treatment with miR-10a-5p mimics allowed miR-10a-5p enrichment and resulted in a significant restriction in PHEV replication, suggesting widespread negative regulation of the RNA virus infection by miR-10a-5p. The outcomes were also evidenced by miR-10a-5p inhibitor over-expression. Luciferase reporter, quantitative real-time PCR (qRT-PCR), and western blotting analysis further showed that Syndecan 1 (SDC1), a cell surface proteoglycan associated with host defense mechanisms, acts as a target gene of miR-10a-5p during PHEV infection. Naturally, siRNA-mediated knockdown of SDC1 leads to a reduction in viral replication, implying that SDC1 expression is likely a favorable condition for viral replication. Together, the findings demonstrated that the abundant miR-10a-5p leads to downstream suppression of SDC1, and it functions as an antiviral mechanism in the PHEV-induced disease, providing a potential strategy for the prevention and treatment of PHEV infection in the future work.",2020 Feb 20,"['Hu, Shiyu', 'Li, Zi', 'Lan, Yungang', 'Guan, Jiyu', 'Zhao, Kui', 'Chu, Dianfeng', 'Fan, Gencheng', 'Guo, Yuguang', 'Gao, Feng', 'He, Wenqi']",Front Microbiol,,,True
9d63191505e7cdb2dc1436228923fc97515e2ea1,PMC,16S rRNA gene sequencing reveals an altered composition of the gut microbiota in chickens infected with a nephropathogenic infectious bronchitis virus,http://dx.doi.org/10.1038/s41598-020-60564-8,PMC7044311,32103130,CC BY,"Infectious bronchitis virus (IBV), a member of the Coronaviridae family, causes serious losses to the poultry industry. Intestinal microbiota play an important role in chicken health and contribute to the defence against colonization by invading pathogens. The aim of this study was to investigate the link between the intestinal microbiome and nephropathogenic IBV (NIBV) infection. Initially, chickens were randomly distributed into 2 groups: the normal group (INC) and the infected group (IIBV). The ilea were collected for morphological assessment, and the ileal contents were collected for 16S rRNA gene sequencing analysis. The results of the IIBV group analyses showed a significant decrease in the ratio of villus height to crypt depth (P < 0.05), while the goblet cells increased compared to those in the INC group. Furthermore, the microbial diversity in the ilea decreased and overrepresentation of Enterobacteriaceae and underrepresentation of Chloroplast and Clostridia was found in the NIBV-infected chickens. In conclusion, these results showed that the significant separation of the two groups and the characterization of the gut microbiome profiles of the chickens with NIBV infection may provide valuable information and promising biomarkers for the diagnosis of this disease.",2020 Feb 26,"['Xu, Puzhi', 'Shi, Yan', 'Liu, Ping', 'Yang, Yitian', 'Zhou, Changming', 'Li, Guyue', 'Luo, Junrong', 'Zhang, Caiying', 'Cao, Huabin', 'Hu, Guoliang', 'Guo, Xiaoquan']",Sci Rep,,,True
fca0580d965f2ac6c66e345eab40c436d6468c66,PMC,Assessment of correlates of hand hygiene compliance among final year medical students: a cross-sectional study in the Netherlands,http://dx.doi.org/10.1136/bmjopen-2019-029484,PMC7045092,32054622,CC BY,"OBJECTIVES: To identify the factors that influence the hand hygiene compliance of final year medical students, using a theoretical behavioural framework. DESIGN: Cross-sectional survey assessing self-reported compliance and its behavioural correlates. SETTING: Internships of medical students in the Netherlands. PARTICIPANTS: 322 medical students of the Erasmus Medical Center were recruited over a period of 12 months during the Public Health internship, which is the final compulsory internship after an 18-month rotation schedule in all major specialities. PRIMARY AND SECONDARY OUTCOME MEASURES: Behavioural factors influencing compliance to hand hygiene guidelines were measured by means of a questionnaire based on the Theory of Planned Behaviour and Social Ecological Models. Multiple linear regression analysis was used to identify the effect of including attitudes, social norms, self-efficacy, knowledge, risk perception and habit on hand hygiene compliance. RESULTS: We included 313 students in the analysis (response rate 97%). The behavioural model explained 40% of the variance in self-reported compliance (adjusted R(2)=0.40). Hand hygiene compliance was strongly influenced by attitudes (perceived outcomes of preventive actions), self-efficacy (perception of the ability to perform hand hygiene at the clinical ward) and habit, but was not associated with knowledge and risk perception. CONCLUSIONS: Targeting medical students’ behaviour should focus on the empowerment of these juniors and provide them with evidence on the health benefits of prevention, rather than increasing their factual knowledge of procedures. Clinical teaching environments could help them form good patient safety habits during this vital phase of their career.",2020 Feb 12,"['Erasmus, Vicki', 'Otto, Suzie', 'De Roos, Emmely', 'van Eijsden, Rianne', 'Vos, Margreet C', 'Burdorf, Alex', 'van Beeck, Ed']",BMJ Open,,,True
334dad2c93659c3ffac791c39b0282e7fbe18c52,PMC,Assessment of correlates of hand hygiene compliance among final year medical students: a cross-sectional study in the Netherlands,http://dx.doi.org/10.1136/bmjopen-2019-029484,PMC7045092,32054622,CC BY,"OBJECTIVES: To identify the factors that influence the hand hygiene compliance of final year medical students, using a theoretical behavioural framework. DESIGN: Cross-sectional survey assessing self-reported compliance and its behavioural correlates. SETTING: Internships of medical students in the Netherlands. PARTICIPANTS: 322 medical students of the Erasmus Medical Center were recruited over a period of 12 months during the Public Health internship, which is the final compulsory internship after an 18-month rotation schedule in all major specialities. PRIMARY AND SECONDARY OUTCOME MEASURES: Behavioural factors influencing compliance to hand hygiene guidelines were measured by means of a questionnaire based on the Theory of Planned Behaviour and Social Ecological Models. Multiple linear regression analysis was used to identify the effect of including attitudes, social norms, self-efficacy, knowledge, risk perception and habit on hand hygiene compliance. RESULTS: We included 313 students in the analysis (response rate 97%). The behavioural model explained 40% of the variance in self-reported compliance (adjusted R(2)=0.40). Hand hygiene compliance was strongly influenced by attitudes (perceived outcomes of preventive actions), self-efficacy (perception of the ability to perform hand hygiene at the clinical ward) and habit, but was not associated with knowledge and risk perception. CONCLUSIONS: Targeting medical students’ behaviour should focus on the empowerment of these juniors and provide them with evidence on the health benefits of prevention, rather than increasing their factual knowledge of procedures. Clinical teaching environments could help them form good patient safety habits during this vital phase of their career.",2020 Feb 12,"['Erasmus, Vicki', 'Otto, Suzie', 'De Roos, Emmely', 'van Eijsden, Rianne', 'Vos, Margreet C', 'Burdorf, Alex', 'van Beeck, Ed']",BMJ Open,,,True
f7955bd0f0bef58a43cc6bb253442f198aa00fbb,PMC,Assessment of correlates of hand hygiene compliance among final year medical students: a cross-sectional study in the Netherlands,http://dx.doi.org/10.1136/bmjopen-2019-029484,PMC7045092,32054622,CC BY,"OBJECTIVES: To identify the factors that influence the hand hygiene compliance of final year medical students, using a theoretical behavioural framework. DESIGN: Cross-sectional survey assessing self-reported compliance and its behavioural correlates. SETTING: Internships of medical students in the Netherlands. PARTICIPANTS: 322 medical students of the Erasmus Medical Center were recruited over a period of 12 months during the Public Health internship, which is the final compulsory internship after an 18-month rotation schedule in all major specialities. PRIMARY AND SECONDARY OUTCOME MEASURES: Behavioural factors influencing compliance to hand hygiene guidelines were measured by means of a questionnaire based on the Theory of Planned Behaviour and Social Ecological Models. Multiple linear regression analysis was used to identify the effect of including attitudes, social norms, self-efficacy, knowledge, risk perception and habit on hand hygiene compliance. RESULTS: We included 313 students in the analysis (response rate 97%). The behavioural model explained 40% of the variance in self-reported compliance (adjusted R(2)=0.40). Hand hygiene compliance was strongly influenced by attitudes (perceived outcomes of preventive actions), self-efficacy (perception of the ability to perform hand hygiene at the clinical ward) and habit, but was not associated with knowledge and risk perception. CONCLUSIONS: Targeting medical students’ behaviour should focus on the empowerment of these juniors and provide them with evidence on the health benefits of prevention, rather than increasing their factual knowledge of procedures. Clinical teaching environments could help them form good patient safety habits during this vital phase of their career.",2020 Feb 12,"['Erasmus, Vicki', 'Otto, Suzie', 'De Roos, Emmely', 'van Eijsden, Rianne', 'Vos, Margreet C', 'Burdorf, Alex', 'van Beeck, Ed']",BMJ Open,,,False
c351ce11cb0157d1118dfcbb55cf9f8bab0ad35d,PMC,A realistic two-strain model for MERS-CoV infection uncovers the high risk for epidemic propagation,http://dx.doi.org/10.1371/journal.pntd.0008065,PMC7046297,32059047,CC BY,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory illness with a case fatality rate (CFR) of 35,5%. The highest number of MERS-CoV cases are from Saudi-Arabia, the major worldwide hotspot for this disease. In the absence of neither effective treatment nor a ready-to-use vaccine and with yet an incomplete understanding of its epidemiological cycle, prevention and containment measures can be derived from mathematical models of disease epidemiology. We constructed 2-strain models to predict past outbreaks in the interval 2012–2016 and derive key epidemiological information for Macca, Madina and Riyadh. We approached variability in infection through three different disease incidence functions capturing social behavior in response to an epidemic (e.g. Bilinear, BL; Non-monotone, NM; and Saturated, SAT models). The best model combination successfully anticipated the total number of MERS-CoV clinical cases for the 2015–2016 season and accurately predicted both the number of cases at the peak of seasonal incidence and the overall shape of the epidemic cycle. The evolution in the basic reproduction number (R(0)) warns that MERS-CoV may easily take an epidemic form. The best model correctly captures this feature, indicating a high epidemic risk (1≤R(0)≤2,5) in Riyadh and Macca and confirming the alleged co-circulation of more than one strain. Accurate predictions of the future MERS-CoV peak week, as well as the number of cases at the peak are now possible. These results indicate public health agencies should be aware that measures for strict containment are urgently needed before new epidemics take off in the region.",2020 Feb 14,"['Sardar, Tridip', 'Ghosh, Indrajit', 'Rodó, Xavier', 'Chattopadhyay, Joydev']",PLoS Negl Trop Dis,,,True
9788dc8167b08ed6cfba73a0a4606b5e53bc5e37,PMC,Emerging zoonoses: A one health challenge,http://dx.doi.org/10.1016/j.eclinm.2020.100300,PMC7046497,32140676,CC BY,,2020 Feb 26,,EClinicalMedicine,,,False
b7fe30b45be18287177cb44e2add69ae4ba54486,PMC,In this month’s Bulletin,http://dx.doi.org/10.2471/BLT.20.000320,PMC7047026,,CC BY,,2020 Mar 1,,Bull World Health Organ,,,False
7fd305aac7f42ec53e85db85ac74f2d2a8ba8dd6,PMC,Data sharing for novel coronavirus (COVID-19),http://dx.doi.org/10.2471/BLT.20.251561,PMC7047033,32132744,CC BY,,2020 Mar 1,"['Moorthy, Vasee', 'Henao Restrepo, Ana Maria', 'Preziosi, Marie-Pierre', 'Swaminathan, Soumya']",Bull World Health Organ,,,True
abb1c76b75ee9533b66c235f6fafdd95489cc414,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.20.010320,PMC7047037,32132747,CC BY,,2020 Mar 1,,Bull World Health Organ,,,False
78360444f3b4540339efc9e7e5f2610a7e46c023,PMC,Q&A: The novel coronavirus outbreak causing COVID-19,http://dx.doi.org/10.1186/s12916-020-01533-w,PMC7047369,32106852,CC BY,,2020 Feb 28,"['Fisher, Dale', 'Heymann, David']",BMC Med,,,True
018269476cd191365d6b8bed046078aea07c8c01,PMC,A mathematical model for simulating the phase-based transmissibility of a novel coronavirus,http://dx.doi.org/10.1186/s40249-020-00640-3,PMC7047374,32111262,CC BY,"BACKGROUND: As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. The virus was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by International Committee on Taxonomy of Viruses on 11 February, 2020. This study aimed to develop a mathematical model for calculating the transmissibility of the virus. METHODS: In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probably be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market (reservoir) to people, we simplified the model as Reservoir-People (RP) transmission network model. The next generation matrix approach was adopted to calculate the basic reproduction number (R(0)) from the RP model to assess the transmissibility of the SARS-CoV-2. RESULTS: The value of R(0) was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58. CONCLUSIONS: Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries, similar to severe acute respiratory syndrome, but lower than MERS in the Republic of Korea.",2020 Feb 28,"['Chen, Tian-Mu', 'Rui, Jia', 'Wang, Qiu-Peng', 'Zhao, Ze-Yu', 'Cui, Jing-An', 'Yin, Ling']",Infect Dis Poverty,,,True
b676de09cf12905dea5d204930150599d5256cde,PMC,A Bayesian approach for detecting a disease that is not being modeled,http://dx.doi.org/10.1371/journal.pone.0229658,PMC7048291,32109254,CC BY,"Over the past decade, outbreaks of new or reemergent viruses such as severe acute respiratory syndrome (SARS) virus, Middle East respiratory syndrome (MERS) virus, and Zika have claimed thousands of lives and cost governments and healthcare systems billions of dollars. Because the appearance of new or transformed diseases is likely to continue, the detection and characterization of emergent diseases is an important problem. We describe a Bayesian statistical model that can detect and characterize previously unknown and unmodeled diseases from patient-care reports and evaluate its performance on historical data.",2020 Feb 28,"['Aronis, John M.', 'Ferraro, Jeffrey P.', 'Gesteland, Per H.', 'Tsui, Fuchiang', 'Ye, Ye', 'Wagner, Michael M.', 'Cooper, Gregory F.']",PLoS One,,,True
427e89aef2f0493c243bff2260969a8f845308da,PMC,A Bayesian approach for detecting a disease that is not being modeled,http://dx.doi.org/10.1371/journal.pone.0229658,PMC7048291,32109254,CC BY,"Over the past decade, outbreaks of new or reemergent viruses such as severe acute respiratory syndrome (SARS) virus, Middle East respiratory syndrome (MERS) virus, and Zika have claimed thousands of lives and cost governments and healthcare systems billions of dollars. Because the appearance of new or transformed diseases is likely to continue, the detection and characterization of emergent diseases is an important problem. We describe a Bayesian statistical model that can detect and characterize previously unknown and unmodeled diseases from patient-care reports and evaluate its performance on historical data.",2020 Feb 28,"['Aronis, John M.', 'Ferraro, Jeffrey P.', 'Gesteland, Per H.', 'Tsui, Fuchiang', 'Ye, Ye', 'Wagner, Michael M.', 'Cooper, Gregory F.']",PLoS One,,,False
3e7042ac51bcdbd64db05d998292e8ed45ebfc07,PMC,Structure of the host cell recognition and penetration machinery of a Staphylococcus aureus bacteriophage,http://dx.doi.org/10.1371/journal.ppat.1008314,PMC7048315,32069326,CC0,"Staphylococcus aureus is a common cause of infections in humans. The emergence of virulent, antibiotic-resistant strains of S. aureus is a significant public health concern. Most virulence and resistance factors in S. aureus are encoded by mobile genetic elements, and transduction by bacteriophages represents the main mechanism for horizontal gene transfer. The baseplate is a specialized structure at the tip of bacteriophage tails that plays key roles in host recognition, cell wall penetration, and DNA ejection. We have used high-resolution cryo-electron microscopy to determine the structure of the S. aureus bacteriophage 80α baseplate at 3.75 Å resolution, allowing atomic models to be built for most of the major tail and baseplate proteins, including two tail fibers, the receptor binding protein, and part of the tape measure protein. Our structure provides a structural basis for understanding host recognition, cell wall penetration and DNA ejection in viruses infecting Gram-positive bacteria. Comparison to other phages demonstrates the modular design of baseplate proteins, and the adaptations to the host that take place during the evolution of staphylococci and other pathogens.",2020 Feb 18,"['Kizziah, James L.', 'Manning, Keith A.', 'Dearborn, Altaira D.', 'Dokland, Terje']",PLoS Pathog,,,True
3f73c3375dc23ff5ae0342af92a57a9a3256f8f3,PMC,Structure of the host cell recognition and penetration machinery of a Staphylococcus aureus bacteriophage,http://dx.doi.org/10.1371/journal.ppat.1008314,PMC7048315,32069326,CC0,"Staphylococcus aureus is a common cause of infections in humans. The emergence of virulent, antibiotic-resistant strains of S. aureus is a significant public health concern. Most virulence and resistance factors in S. aureus are encoded by mobile genetic elements, and transduction by bacteriophages represents the main mechanism for horizontal gene transfer. The baseplate is a specialized structure at the tip of bacteriophage tails that plays key roles in host recognition, cell wall penetration, and DNA ejection. We have used high-resolution cryo-electron microscopy to determine the structure of the S. aureus bacteriophage 80α baseplate at 3.75 Å resolution, allowing atomic models to be built for most of the major tail and baseplate proteins, including two tail fibers, the receptor binding protein, and part of the tape measure protein. Our structure provides a structural basis for understanding host recognition, cell wall penetration and DNA ejection in viruses infecting Gram-positive bacteria. Comparison to other phages demonstrates the modular design of baseplate proteins, and the adaptations to the host that take place during the evolution of staphylococci and other pathogens.",2020 Feb 18,"['Kizziah, James L.', 'Manning, Keith A.', 'Dearborn, Altaira D.', 'Dokland, Terje']",PLoS Pathog,,,False
cfdebdd5e1bb6824451bd0336a8955201fc56589,PMC,Structure of the host cell recognition and penetration machinery of a Staphylococcus aureus bacteriophage,http://dx.doi.org/10.1371/journal.ppat.1008314,PMC7048315,32069326,CC0,"Staphylococcus aureus is a common cause of infections in humans. The emergence of virulent, antibiotic-resistant strains of S. aureus is a significant public health concern. Most virulence and resistance factors in S. aureus are encoded by mobile genetic elements, and transduction by bacteriophages represents the main mechanism for horizontal gene transfer. The baseplate is a specialized structure at the tip of bacteriophage tails that plays key roles in host recognition, cell wall penetration, and DNA ejection. We have used high-resolution cryo-electron microscopy to determine the structure of the S. aureus bacteriophage 80α baseplate at 3.75 Å resolution, allowing atomic models to be built for most of the major tail and baseplate proteins, including two tail fibers, the receptor binding protein, and part of the tape measure protein. Our structure provides a structural basis for understanding host recognition, cell wall penetration and DNA ejection in viruses infecting Gram-positive bacteria. Comparison to other phages demonstrates the modular design of baseplate proteins, and the adaptations to the host that take place during the evolution of staphylococci and other pathogens.",2020 Feb 18,"['Kizziah, James L.', 'Manning, Keith A.', 'Dearborn, Altaira D.', 'Dokland, Terje']",PLoS Pathog,,,False
3e4de1d7982eb2ce67d340a63175adfdab398686,PMC,Distribution and genetic diversity of adeno-associated viruses in bats from coastal areas of Southeast China,http://dx.doi.org/10.1038/s41598-020-60721-z,PMC7048818,32111911,CC BY,"Bats are associated with several important zoonotic viruses from different families. One example includes adeno-associated viruses (AAVs), that are extensively detected in several animals, especially primates. To understand AAVs distribution and genetic diversity in the coastal areas of Southeast China, a total of 415 intestine samples were mostly collected from two provinces of southeast China, i.e., Zhejiang and Fujian province. Intestine samples from five bat species were collected for AAVs detection. The average prevalence rate for AAV detection among these samples was 18.6% (77 positives out of 415 samples) and ranged from 11.8 to 28.9% between the five bat species. This suggests that AAVs are widely distributed in diverse bat populations in southeast coastal areas of China. Based on the genome sequence of bat adeno-associated virus-CXC1(BtAAV-CXC1) from one AAV-positive sample, the genetic diversity of the detected AAVs were assessed and analyzed. Phylogenetic analysis revealed that BtAAV-CXC1 was comparatively distant to other major AAVs from mammals and non-mammals, with only a 52.9~64.7% nucleotide identity. However, they were phylogenetically closer to Rhinolophus sinicus bat adeno-associated virus (Rs-BtAAV1), with a 74.5% nt similarity. Partial analysis of the rep and cap overlapping open reading frame (ORF) sequences from bat AAV samples revealed 48 partial rep sequences and 23 partial cap sequences from positive samples shared 86.9 to 100% and 72.3 to 98.8% nucleotide identities among themselves, respectively. This suggests that the detected AAVs had a distinctly high genetic diversity. These findings led us to conclude that diverse AAVs may be widely distributed in bat populations from the southeast regions of China.",2020 Feb 28,"['Zhu, Changqiang', 'Wang, Chunhui', 'Wu, Jiahong', 'Ye, Fuqiang', 'Lv, Ruichen', 'Hu, Dan', 'Ai, Lele', 'Yang, Lu', 'Wu, Ting', 'Li, Bo', 'Ding, Chenxi', 'Zhang, Bin', 'Lv, Heng', 'Wang, Changjun', 'Tan, Weilong']",Sci Rep,,,True
7e0925a800d4d09380ac44584b5be257d83531d3,PMC,Molecular Diagnosis of Pneumonia Using Multiplex Real-Time PCR Assay RespiFinder® SMART 22 FAST in a Group of Moroccan Infants,http://dx.doi.org/10.1155/2020/6212643,PMC7049438,32148499,CC BY,"BACKGROUND: In Morocco, pediatric pneumonia remains a serious public health problem, as it constitutes the first cause of mortality due to infectious diseases. The etiological diagnosis of acute respiratory tract infections is difficult. Therefore, it is necessary to use Multiplex real-time polymerase chain reaction assay tests in a routine setting for exact and fast identification. OBJECTIVES: In this paper, we present the clinical results of pediatric pneumonia and describe their etiology by using molecular diagnosis. Study design: Tracheal secretion was collected from infants presenting respiratory distress isolated or associated with systemic signs, attending the unit of Neonatology between December 1, 2016, and Mai 31, 2018. Samples were tested with the multiplex RespiFinder® SMART 22 FAST which potentially detects 18 viruses and 4 bacteria. RESULTS: Of the 86 infants considered in this study (mean age 31 ± 19 days) suspected of acute respiratory tract infections, 71 (83%) were positive for one or multiple viruses or/and bacteria. The majority of acute respiratory tract infections had a viral origin (95%): respiratory syncytial viruses (A and B) (49%), rhinovirus (21%), coronaviruses 229E (11%), humain metapneumovirus (5%), influenza A (3%), influenza H1N1 (1%), adenovirus (2%), and parainfluenza virus type 4 (2%). Among our patients, 6% had Mycoplasma pneumoniae. Coinfections were not associated with severe respiratory symptoms. CONCLUSION: The clinical spectrum of respiratory infections is complex and often nonspecific. Thus, the early and fast detection of related causative agents is crucial. The use of multiplex real time polymerase chain reaction may help choose an accurate treatment, reduce the overall use of unnecessary antibiotics, preserve intestinal flora, and decrease nosocomial infection by reducing the length of hospitalization.",2020 Feb 18,"['Hattoufi, Kenza', 'Tligui, Houssain', 'Obtel, Majdouline', 'El Ftouh, Sobha', 'Kharbach, Aicha', 'Barkat, Amina']",Adv Virol,,,True
b9fe40055b01585084db291401c57f26d25fe478,PMC,"Modelling the effective reproduction number of vector-borne diseases: the yellow fever outbreak in Luanda, Angola 2015–2016 as an example",http://dx.doi.org/10.7717/peerj.8601,PMC7049463,32149023,CC BY,"The burden of vector-borne diseases (Dengue, Zika virus, yellow fever, etc.) gradually increased in the past decade across the globe. Mathematical modelling on infectious diseases helps to study the transmission dynamics of the pathogens. Theoretically, the diseases can be controlled and eventually eradicated by maintaining the effective reproduction number, ([Image: see text] ), strictly less than 1. We established a vector-host compartmental model, and derived ([Image: see text] ) for vector-borne diseases. The analytic form of the ([Image: see text] ) was found to be the product of the basic reproduction number and the geometric average of the susceptibilities of the host and vector populations. The ([Image: see text] ) formula was demonstrated to be consistent with the estimates of the 2015–2016 yellow fever outbreak in Luanda, and distinguished the second minor epidemic wave. For those using the compartmental model to study the vector-borne infectious disease epidemics, we further remark that it is important to be aware of whether one or two generations is considered for the transition “from host to vector to host” in reproduction number calculation.",2020 Feb 27,"['Zhao, Shi', 'Musa, Salihu S.', 'Hebert, Jay T.', 'Cao, Peihua', 'Ran, Jinjun', 'Meng, Jiayi', 'He, Daihai', 'Qin, Jing']",PeerJ,,,True
edee452881f826fb72c58ee68a982789b12aa99d,PMC,Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory,http://dx.doi.org/10.1155/2020/9629747,PMC7049846,32149148,CC BY,"Introduction. Middle East respiratory syndrome coronavirus was first recognized in September 2012 in Saudi Arabia. The clinical presentations of MERS and non-MERS SARI are often similar. Therefore, the identification of suspected cases that may have higher chances of being diagnosed as cases of MERS-CoV is essential. However, the real challenge is to flag these patients through some demographic markers. The nature of these markers has not previously been investigated in Saudi Arabia, and hence, this study aims to identify them. METHODS: It was a surveillance system-based study, for which data from a total of 23,646 suspected patients in Riyadh and Al Qassim regions were analyzed from January 2017 until December 2017 to estimate the prevalence of MERS-CoV among suspected cases and to determine potential demographic risk factors related to the confirmation of the diagnosis. RESULTS: Of 23,646 suspected cases, 119 (0.5%) were confirmed by laboratory results. These confirmed cases (67.2% of which were males) had a mean age of 43.23 years (SD ± 22.8). Around 42.2% of the confirmed cases were aged between 41 and 60 years and about 47% of confirmed cases had their suspected specimen tested in the summer. The study identified three significant and independent predictors for confirmation of the disease: an age between 41 and 60 years, male gender, and summer season admission. CONCLUSION: The study provides evidence that the MERS-CoV epidemic in the subject regions has specific characteristics that might help future plans for the prevention and management of such a contagious disease. Future studies should aim to confirm such findings in other regions of Saudi Arabia as well and explore potential preventable risk factors.",2020 Feb 19,"['Altamimi, Asmaa', 'Abu-Saris, Raghib', 'El-Metwally, Ashraf', 'Alaifan, Taghreed', 'Alamri, Aref']",Biomed Res Int,,,True
7fb385f3c0c5ce04f1c3d3c4f20678c0ae3a7031,PMC,"Development and validation of knowledge, attitude and practice questionnaire for prevention of respiratory tract infections among Malaysian Hajj pilgrims",http://dx.doi.org/10.1186/s12889-020-8269-9,PMC7050115,32114986,CC BY,"BACKGROUND: Hajj pilgrimage faces numerous challenges including a high prevalence of respiratory tract infection as well as its prevention strategies. The aim of this study was to develop and validate a questionnaire to evaluate knowledge, attitude and practice (KAP) towards respiratory tract infections (RTIs) prevention among Malaysian Hajj pilgrims. METHODS: This study was conducted among Malaysian Umrah pilgrims in Malaysia from Kuala Lumpur and Kelantan. The questionnaire then underwent a series of validation process that included content, face validity and exploratory part. Item response theory (IRT) analysis was utilized for the validation of the knowledge domain. The attitude and practice were validated using the exploratory factor analysis (EFA). RESULTS: The validation process resulted in a questionnaire that comprised of four main sections: demography, knowledge, attitude, and practice. Following IRT analysis of the knowledge domain, all items analyzed were within the acceptable range of difficulty and discrimination. The Kaiser-Meyer-Olkin measure of sampling adequacy (KMO) was 0.72 and 0.84 for attitude and practice domain respectively and Bartlett’s test of Sphericity for both domains were highly significant (P < 0.001). The factor analysis resulted in two factors with total of 12 items in attitude domain, and 2 factors with total of 13 items in the practice domain with satisfactory factor loading (> 0.3). The Cronbach’s alpha for reliability of the knowledge, attitude and practice domains all showed acceptable values of > 0.6 (0.92, 0.77 and 0.85). CONCLUSION: The findings of this validation and reliability study showed that the developed questionnaire had a satisfactory psychometric property for measuring KAP of Malaysian Hajj pilgrims.",2020 Mar 2,"['Goni, Mohammed Dauda', 'Naing, Nyi Nyi', 'Hasan, Habsah', 'Wan-Arfah, Nadiah', 'Deris, Zakuan Zainy', 'Arifin, Wan Nor', 'Hussin, Tengku Mohammad Ariff Raja', 'Abdulrahman, Abdulwali Sabo', 'Baaba, Aisha Abubakar', 'Arshad, Muhammad Rafie']",BMC Public Health,,,True
e5a10a7f2c9bb07f74fcce076a62f63f859cf3a4,PMC,Global Critical Care: Moving Forward in Resource-Limited Settings,http://dx.doi.org/10.5334/aogh.2413,PMC7052346,30741504,CC BY,"Caring for critically ill patients is challenging in resource-limited settings, where the burden of disease and mortality from potentially treatable illnesses is higher than in resource-rich areas. Barriers to delivering quality critical care in these settings include lack of epidemiologic data and context-specific evidence for medical decision-making, deficiencies in health systems organization and resources, and institutional obstacles to implementation of life-saving interventions. Potential solutions include the development of common definitions for intensive care unit (ICU), intensivist, and intensive care to create a universal ICU organization framework; development of educational programs for capacity building of health care professionals working in resource-limited settings; global prioritization of epidemiologic and clinical research in resource-limited settings to conduct timely and ethical studies in response to emerging threats; adaptation of international guidelines to promote implementation of evidence-based care; and strengthening of health systems that integrates these interventions. This manuscript reviews the field of global critical care, barriers to safe high-quality care, and potential solutions to existing challenges. We also suggest a roadmap for improving the treatment of critically ill patients in resource-limited settings.",,"['Diaz, Janet V.', 'Riviello, Elisabeth D.', 'Papali, Alfred', 'Adhikari, Neill K. J.', 'Ferreira, Juliana C.']",Ann Glob Health.; 85(1):3,,,True
d52f110a68d9cedde89f2e523e072bcecd51dcab,PMC,Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro,http://dx.doi.org/10.1038/s41422-020-0282-0,PMC7054408,32020029,CC BY,,2020 Mar 4,"['Wang, Manli', 'Cao, Ruiyuan', 'Zhang, Leike', 'Yang, Xinglou', 'Liu, Jia', 'Xu, Mingyue', 'Shi, Zhengli', 'Hu, Zhihong', 'Zhong, Wu', 'Xiao, Gengfu']",Cell Res,,,False
acb678bdd7634055de18d0b89bb6a4890e6a0306,PMC,Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro,http://dx.doi.org/10.1038/s41422-020-0282-0,PMC7054408,32020029,CC BY,,2020 Mar 4,"['Wang, Manli', 'Cao, Ruiyuan', 'Zhang, Leike', 'Yang, Xinglou', 'Liu, Jia', 'Xu, Mingyue', 'Shi, Zhengli', 'Hu, Zhihong', 'Zhong, Wu', 'Xiao, Gengfu']",Cell Res,,,True
a70e7c4d8ee484ce956e91c8700d0c9310bbdbbc,PMC,Estimated effectiveness of symptom and risk screening to prevent the spread of COVID-19,http://dx.doi.org/10.7554/eLife.55570,PMC7060038,32091395,CC BY,"Traveller screening is being used to limit further spread of COVID-19 following its recent emergence, and symptom screening has become a ubiquitous tool in the global response. Previously, we developed a mathematical model to understand factors governing the effectiveness of traveller screening to prevent spread of emerging pathogens (Gostic et al., 2015). Here, we estimate the impact of different screening programs given current knowledge of key COVID-19 life history and epidemiological parameters. Even under best-case assumptions, we estimate that screening will miss more than half of infected people. Breaking down the factors leading to screening successes and failures, we find that most cases missed by screening are fundamentally undetectable, because they have not yet developed symptoms and are unaware they were exposed. Our work underscores the need for measures to limit transmission by individuals who become ill after being missed by a screening program. These findings can support evidence-based policy to combat the spread of COVID-19, and prospective planning to mitigate future emerging pathogens.",,"['Gostic, Katelyn', 'Gomez, Ana CR', 'Mummah, Riley O', 'Kucharski, Adam J', 'Lloyd-Smith, James O']",eLife.; 9:e55570,,,True
7e4cd1fd8b248bf8d5609751a2c3c32240e5b592,PMC,Estimated effectiveness of symptom and risk screening to prevent the spread of COVID-19,http://dx.doi.org/10.7554/eLife.55570,PMC7060038,32091395,CC BY,"Traveller screening is being used to limit further spread of COVID-19 following its recent emergence, and symptom screening has become a ubiquitous tool in the global response. Previously, we developed a mathematical model to understand factors governing the effectiveness of traveller screening to prevent spread of emerging pathogens (Gostic et al., 2015). Here, we estimate the impact of different screening programs given current knowledge of key COVID-19 life history and epidemiological parameters. Even under best-case assumptions, we estimate that screening will miss more than half of infected people. Breaking down the factors leading to screening successes and failures, we find that most cases missed by screening are fundamentally undetectable, because they have not yet developed symptoms and are unaware they were exposed. Our work underscores the need for measures to limit transmission by individuals who become ill after being missed by a screening program. These findings can support evidence-based policy to combat the spread of COVID-19, and prospective planning to mitigate future emerging pathogens.",,"['Gostic, Katelyn', 'Gomez, Ana CR', 'Mummah, Riley O', 'Kucharski, Adam J', 'Lloyd-Smith, James O']",eLife.; 9:e55570,,,False
c1ad13d83e926979dbf2bbe52e4944082f28dfea,PMC,Antisense-induced ribosomal frameshifting,http://dx.doi.org/10.1093/nar/gkl531,PMC1616946,16920740,CC BY-NC,"Programmed ribosomal frameshifting provides a mechanism to decode information located in two overlapping reading frames by diverting a proportion of translating ribosomes into a second open reading frame (ORF). The result is the production of two proteins: the product of standard translation from ORF1 and an ORF1–ORF2 fusion protein. Such programmed frameshifting is commonly utilized as a gene expression mechanism in viruses that infect eukaryotic cells and in a subset of cellular genes. RNA secondary structures, consisting of pseudoknots or stem–loops, located downstream of the shift site often act as cis-stimulators of frameshifting. Here, we demonstrate for the first time that antisense oligonucleotides can functionally mimic these RNA structures to induce +1 ribosomal frameshifting when annealed downstream of the frameshift site, UCC UGA. Antisense-induced shifting of the ribosome into the +1 reading frame is highly efficient in both rabbit reticulocyte lysate translation reactions and in cultured mammalian cells. The efficiency of antisense-induced frameshifting at this site is responsive to the sequence context 5′ of the shift site and to polyamine levels.",2006 Sep 18,"['Henderson, Clark M.', 'Anderson, Christine B.', 'Howard, Michael T.']",Nucleic Acids Res,,,True
25fd0362dfe0a62ca9ee6f9f634e24ef9a527dfc,PMC,The gene of an archaeal α-l-fucosidase is expressed by translational frameshifting,http://dx.doi.org/10.1093/nar/gkl574,PMC1616953,16920738,CC BY-NC,"The standard rules of genetic translational decoding are altered in specific genes by different events that are globally termed recoding. In Archaea recoding has been unequivocally determined so far only for termination codon readthrough events. We study here the mechanism of expression of a gene encoding for a α-l-fucosidase from the archaeon Sulfolobus solfataricus (fucA1), which is split in two open reading frames separated by a −1 frameshifting. The expression in Escherichia coli of the wild-type split gene led to the production by frameshifting of full-length polypeptides with an efficiency of 5%. Mutations in the regulatory site where the shift takes place demonstrate that the expression in vivo occurs in a programmed way. Further, we identify a full-length product of fucA1 in S.solfataricus extracts, which translate this gene in vitro by following programmed −1 frameshifting. This is the first experimental demonstration that this kind of recoding is present in Archaea.",2006 Sep 18,"['Cobucci-Ponzano, Beatrice', 'Conte, Fiorella', 'Benelli, Dario', 'Londei, Paola', 'Flagiello, Angela', 'Monti, Maria', 'Pucci, Piero', 'Rossi, Mosè', 'Moracci, Marco']",Nucleic Acids Res,,,True
d230ca9dcc54e1d5c0ed4503752774eb44711dff,PMC,Role of RNA helicases in HIV-1 replication,http://dx.doi.org/10.1093/nar/gkl398,PMC1616970,16935887,CC BY-NC,"Viruses are replication competent genomes which are relatively gene-poor. Even the largest viruses (i.e. Herpesviruses) encode only slightly >200 open reading frames (ORFs). However, because viruses replicate obligatorily inside cells, and considering that evolution may be driven by a principle of economy of scale, it is reasonable to surmise that many viruses have evolved the ability to co-opt cell-encoded proteins to provide needed surrogate functions. An in silico survey of viral sequence databases reveals that most positive-strand and double-stranded RNA viruses have ORFs for RNA helicases. On the other hand, the genomes of retroviruses are devoid of virally-encoded helicase. Here, we review in brief the notion that the human immunodeficiency virus (HIV-1) has adopted the ability to use one or more cellular RNA helicases for its replicative life cycle.",2006 Sep 25,"['Jeang, Kuan-Teh', 'Yedavalli, Venkat']",Nucleic Acids Res,,,True
d25529180f950874e0b4f62a976959d683a2ceaf,PMC,Amino acid residues critical for RNA-binding in the N-terminal domain of the nucleocapsid protein are essential determinants for the infectivity of coronavirus in cultured cells,http://dx.doi.org/10.1093/nar/gkl650,PMC1635287,16971454,CC BY-NC,"The N-terminal domain of the coronavirus nucleocapsid (N) protein adopts a fold resembling a right hand with a flexible, positively charged β-hairpin and a hydrophobic palm. This domain was shown to interact with the genomic RNA for coronavirus infectious bronchitis virus (IBV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Based on its 3D structure, we used site-directed mutagenesis to identify residues essential for the RNA-binding activity of the IBV N protein and viral infectivity. Alanine substitution of either Arg-76 or Tyr-94 in the N-terminal domain of IBV N protein led to a significant decrease in its RNA-binding activity and a total loss of the infectivity of the viral RNA to Vero cells. In contrast, mutation of amino acid Gln-74 to an alanine, which does not affect the binding activity of the N-terminal domain, showed minimal, if any, detrimental effect on the infectivity of IBV. This study thus identifies residues critical for RNA binding on the nucleocapsid surface, and presents biochemical and genetic evidence that directly links the RNA binding capacity of the coronavirus N protein to the viral infectivity in cultured cells. This information would be useful in development of preventive and treatment approaches against coronavirus infection.",2006 Oct 13,"['Tan, Yong Wah', 'Fang, Shouguo', 'Fan, Hui', 'Lescar, Julien', 'Liu, D.X.']",Nucleic Acids Res,,,True
4eb6e165ee705e2ae2a24ed2d4e67da42831ff4a,PMC,Automated identification of multiple micro-organisms from resequencing DNA microarrays,http://dx.doi.org/10.1093/nar/gkl565,PMC1636417,17012284,CC BY-NC,"There is an increasing recognition that detailed nucleic acid sequence information will be useful and even required in the diagnosis, treatment and surveillance of many significant pathogens. Because generating detailed information about pathogens leads to significantly larger amounts of data, it is necessary to develop automated analysis methods to reduce analysis time and to standardize identification criteria. This is especially important for multiple pathogen assays designed to reduce assay time and costs. In this paper, we present a successful algorithm for detecting pathogens and reporting the maximum level of detail possible using multi-pathogen resequencing microarrays. The algorithm filters the sequence of base calls from the microarray and finds entries in genetic databases that most closely match. Taxonomic databases are then used to relate these entries to each other so that the microorganism can be identified. Although developed using a resequencing microarray, the approach is applicable to any assay method that produces base call sequence information. The success and continued development of this approach means that a non-expert can now perform unassisted analysis of the results obtained from partial sequence data.",2006 Oct 29,"['Malanoski, Anthony P.', 'Lin, Baochuan', 'Wang, Zheng', 'Schnur, Joel M.', 'Stenger, David A.']",Nucleic Acids Res,,,True
cdcec3941d02aa6c75adfdeb1bbffd91271e6dd7,PMC,Automated identification of multiple micro-organisms from resequencing DNA microarrays,http://dx.doi.org/10.1093/nar/gkl565,PMC1636417,17012284,CC BY-NC,"There is an increasing recognition that detailed nucleic acid sequence information will be useful and even required in the diagnosis, treatment and surveillance of many significant pathogens. Because generating detailed information about pathogens leads to significantly larger amounts of data, it is necessary to develop automated analysis methods to reduce analysis time and to standardize identification criteria. This is especially important for multiple pathogen assays designed to reduce assay time and costs. In this paper, we present a successful algorithm for detecting pathogens and reporting the maximum level of detail possible using multi-pathogen resequencing microarrays. The algorithm filters the sequence of base calls from the microarray and finds entries in genetic databases that most closely match. Taxonomic databases are then used to relate these entries to each other so that the microorganism can be identified. Although developed using a resequencing microarray, the approach is applicable to any assay method that produces base call sequence information. The success and continued development of this approach means that a non-expert can now perform unassisted analysis of the results obtained from partial sequence data.",2006 Oct 29,"['Malanoski, Anthony P.', 'Lin, Baochuan', 'Wang, Zheng', 'Schnur, Joel M.', 'Stenger, David A.']",Nucleic Acids Res,,,False
d4f0247db5e916c20eae3f6d772e8572eb828236,PMC,Automated identification of multiple micro-organisms from resequencing DNA microarrays,http://dx.doi.org/10.1093/nar/gkl565,PMC1636417,17012284,CC BY-NC,"There is an increasing recognition that detailed nucleic acid sequence information will be useful and even required in the diagnosis, treatment and surveillance of many significant pathogens. Because generating detailed information about pathogens leads to significantly larger amounts of data, it is necessary to develop automated analysis methods to reduce analysis time and to standardize identification criteria. This is especially important for multiple pathogen assays designed to reduce assay time and costs. In this paper, we present a successful algorithm for detecting pathogens and reporting the maximum level of detail possible using multi-pathogen resequencing microarrays. The algorithm filters the sequence of base calls from the microarray and finds entries in genetic databases that most closely match. Taxonomic databases are then used to relate these entries to each other so that the microorganism can be identified. Although developed using a resequencing microarray, the approach is applicable to any assay method that produces base call sequence information. The success and continued development of this approach means that a non-expert can now perform unassisted analysis of the results obtained from partial sequence data.",2006 Oct 29,"['Malanoski, Anthony P.', 'Lin, Baochuan', 'Wang, Zheng', 'Schnur, Joel M.', 'Stenger, David A.']",Nucleic Acids Res,,,True
b79db3d6eca01b53a667d32ce59b3f33b40a81ae,PMC,A DNA biochip for on-the-spot multiplexed pathogen identification,http://dx.doi.org/10.1093/nar/gkl702,PMC1636451,17000638,CC BY-NC,"Miniaturized integrated DNA analysis systems have largely been based on a multi-chamber design with microfluidic control to process the sample sequentially from one module to another. This microchip design in connection with optics involved hinders the deployment of this technology for point-of-care applications. In this work, we demonstrate the implementation of sample preparation, DNA amplification, and electrochemical detection in a single silicon and glass-based microchamber and its application for the multiplexed detection of Escherichia coli and Bacillus subtilis cells. The microdevice has a thin-film heater and temperature sensor patterned on the silicon substrate. An array of indium tin oxide (ITO) electrodes was constructed within the microchamber as the transduction element. Oligonucleotide probes specific to the target amplicons are individually positioned at each ITO surface by electrochemical copolymerization of pyrrole and pyrrole−probe conjugate. These immobilized probes were stable to the thermal cycling process and were highly selective. The DNA-based identification of the two model pathogens involved a number of steps including a thermal lysis step, magnetic particle-based isolation of the target genomes, asymmetric PCR, and electrochemical sequence-specific detection using silver-enhanced gold nanoparticles. The microchamber platform described here offers a cost-effective and sample-to-answer technology for on-site monitoring of multiple pathogens.",2006 Oct 25,"['Yeung, Siu-Wai', 'Lee, Thomas Ming-Hung', 'Cai, Hong', 'Hsing, I-Ming']",Nucleic Acids Res,,,True
ad9ac0ac5e7da097253fd545b56e2b15ee9de34f,PMC,Molecular dynamics simulations of human [Formula: see text]: the role of modified bases in mRNA recognition,http://dx.doi.org/10.1093/nar/gkl580,PMC1636460,17012271,CC BY-NC,"Accuracy in translation of the genetic code into proteins depends upon correct tRNA–mRNA recognition in the context of the ribosome. In human [Formula: see text] three modified bases are present in the anticodon stem–loop—2-methylthio-N6-threonylcarbamoyladenosine at position 37 (ms(2)t(6)A37), 5-methoxycarbonylmethyl-2-thiouridine at position 34 (mcm(5)s(2)U34) and pseudouridine (ψ) at position 39—two of which, ms(2)t(6)A37 and mcm(5)s(2)U34, are required to achieve wild-type binding activity of wild-type human [Formula: see text] [C. Yarian, M. Marszalek, E. Sochacka, A. Malkiewicz, R. Guenther, A. Miskiewicz and P. F. Agris (2000) Biochemistry, 39, 13390–13395]. Molecular dynamics simulations of nine tRNA anticodon stem–loops with different combinations of nonstandard bases were performed. The wild-type simulation exhibited a canonical anticodon stair-stepped conformation. The ms(2)t(6) modification at position 37 is required for maintenance of this structure and reduces solvent accessibility of U36. Ms(2)t(6)A37 generally hydrogen bonds across the loop and may prevent U36 from rotating into solution. A water molecule does coordinate to ψ39 most of the simulation time but weakly, as most of the residence lifetimes are <40 ps.",2006 Nov 29,"['McCrate, Nina E.', 'Varner, Mychel E.', 'Kim, Kenneth I.', 'Nagan, Maria C.']",Nucleic Acids Res,,,True
daee7f7d31f4bf1c0ef883bcd6c124b6e94cbee7,PMC,Molecular dynamics simulations of human [Formula: see text]: the role of modified bases in mRNA recognition,http://dx.doi.org/10.1093/nar/gkl580,PMC1636460,17012271,CC BY-NC,"Accuracy in translation of the genetic code into proteins depends upon correct tRNA–mRNA recognition in the context of the ribosome. In human [Formula: see text] three modified bases are present in the anticodon stem–loop—2-methylthio-N6-threonylcarbamoyladenosine at position 37 (ms(2)t(6)A37), 5-methoxycarbonylmethyl-2-thiouridine at position 34 (mcm(5)s(2)U34) and pseudouridine (ψ) at position 39—two of which, ms(2)t(6)A37 and mcm(5)s(2)U34, are required to achieve wild-type binding activity of wild-type human [Formula: see text] [C. Yarian, M. Marszalek, E. Sochacka, A. Malkiewicz, R. Guenther, A. Miskiewicz and P. F. Agris (2000) Biochemistry, 39, 13390–13395]. Molecular dynamics simulations of nine tRNA anticodon stem–loops with different combinations of nonstandard bases were performed. The wild-type simulation exhibited a canonical anticodon stair-stepped conformation. The ms(2)t(6) modification at position 37 is required for maintenance of this structure and reduces solvent accessibility of U36. Ms(2)t(6)A37 generally hydrogen bonds across the loop and may prevent U36 from rotating into solution. A water molecule does coordinate to ψ39 most of the simulation time but weakly, as most of the residence lifetimes are <40 ps.",2006 Nov 29,"['McCrate, Nina E.', 'Varner, Mychel E.', 'Kim, Kenneth I.', 'Nagan, Maria C.']",Nucleic Acids Res,,,True
52566dccb4bd8044edc87b1a0aa268320a6ea3d4,PMC,A novel endonuclease IV post-PCR genotyping system,http://dx.doi.org/10.1093/nar/gkl679,PMC1636472,17012270,CC BY-NC,"Here we describe a novel endonuclease IV (Endo IV) based assay utilizing a substrate that mimics the abasic lesions that normally occur in double-stranded DNA. The three component substrate is characterized by single-stranded DNA target, an oligonucleotide probe, separated from a helper oligonucleotide by a one base gap. The oligonucleotide probe contains a non-fluorescent quencher at the 5′ end and fluorophore attached to the 3′ end through a special rigid linker. Fluorescence of the oligonucleotide probe is efficiently quenched by the interaction of terminal dye and quencher when not hybridized. Upon hybridization of the oligonucleotide probe and helper probe to their complementary target, the phosphodiester linkage between the rigid linker and the 3′ end of the probe is efficiently cleaved, generating a fluorescent signal. In this study, the use of the Endo IV assay as a post-PCR amplification detection system is demonstrated. High sensitivity and specificity are illustrated using single nucleotide polymorphism detection.",2006 Nov 29,"['Kutyavin, Igor V.', 'Milesi, Dave', 'Belousov, Yevgeniy', 'Podyminogin, Mikhail', 'Vorobiev, Alexei', 'Gorn, Vladimir', 'Lukhtanov, Eugeny A.', 'Vermeulen, Nicolaas M. J.', 'Mahoney, Walt']",Nucleic Acids Res,,,True
8b39433dd865c0f71c7b2f333e1f506b73d722f1,PMC,A novel endonuclease IV post-PCR genotyping system,http://dx.doi.org/10.1093/nar/gkl679,PMC1636472,17012270,CC BY-NC,"Here we describe a novel endonuclease IV (Endo IV) based assay utilizing a substrate that mimics the abasic lesions that normally occur in double-stranded DNA. The three component substrate is characterized by single-stranded DNA target, an oligonucleotide probe, separated from a helper oligonucleotide by a one base gap. The oligonucleotide probe contains a non-fluorescent quencher at the 5′ end and fluorophore attached to the 3′ end through a special rigid linker. Fluorescence of the oligonucleotide probe is efficiently quenched by the interaction of terminal dye and quencher when not hybridized. Upon hybridization of the oligonucleotide probe and helper probe to their complementary target, the phosphodiester linkage between the rigid linker and the 3′ end of the probe is efficiently cleaved, generating a fluorescent signal. In this study, the use of the Endo IV assay as a post-PCR amplification detection system is demonstrated. High sensitivity and specificity are illustrated using single nucleotide polymorphism detection.",2006 Nov 29,"['Kutyavin, Igor V.', 'Milesi, Dave', 'Belousov, Yevgeniy', 'Podyminogin, Mikhail', 'Vorobiev, Alexei', 'Gorn, Vladimir', 'Lukhtanov, Eugeny A.', 'Vermeulen, Nicolaas M. J.', 'Mahoney, Walt']",Nucleic Acids Res,,,True
2cf60380bb05becd140053f71fa4cc4e4eaa0d5f,PMC,PATRIC: The VBI PathoSystems Resource Integration Center,http://dx.doi.org/10.1093/nar/gkl858,PMC1669763,17142235,CC BY-NC,"The PathoSystems Resource Integration Center (PATRIC) is one of eight Bioinformatics Resource Centers (BRCs) funded by the National Institute of Allergy and Infection Diseases (NIAID) to create a data and analysis resource for selected NIAID priority pathogens, specifically proteobacteria of the genera Brucella, Rickettsia and Coxiella, and corona-, calici- and lyssaviruses and viruses associated with hepatitis A and E. The goal of the project is to provide a comprehensive bioinformatics resource for these pathogens, including consistently annotated genome, proteome and metabolic pathway data to facilitate research into counter-measures, including drugs, vaccines and diagnostics. The project's curation strategy has three prongs: ‘breadth first’ beginning with whole-genome and proteome curation using standardized protocols, a ‘targeted’ approach addressing the specific needs of researchers and an integrative strategy to leverage high-throughput experimental data (e.g. microarrays, proteomics) and literature. The PATRIC infrastructure consists of a relational database, analytical pipelines and a website which supports browsing, querying, data visualization and the ability to download raw and curated data in standard formats. At present, the site warehouses complete sequences for 17 bacterial and 332 viral genomes. The PATRIC website () will continually grow with the addition of data, analysis and functionality over the course of the project.",2007 Jan 16,"['Snyder, E. E.', 'Kampanya, N.', 'Lu, J.', 'Nordberg, E. K.', 'Karur, H. R.', 'Shukla, M.', 'Soneja, J.', 'Tian, Y.', 'Xue, T.', 'Yoo, H.', 'Zhang, F.', 'Dharmanolla, C.', 'Dongre, N. V.', 'Gillespie, J. J.', 'Hamelius, J.', 'Hance, M.', 'Huntington, K. I.', 'Jukneliene, D.', 'Koziski, J.', 'Mackasmiel, L.', 'Mane, S. P.', 'Nguyen, V.', 'Purkayastha, A.', 'Shallom, J.', 'Yu, G.', 'Guo, Y.', 'Gabbard, J.', 'Hix, D.', 'Azad, A. F.', 'Baker, S. C.', 'Boyle, S. M.', 'Khudyakov, Y.', 'Meng, X. J.', 'Rupprecht, C.', 'Vinje, J.', 'Crasta, O. R.', 'Czar, M. J.', 'Dickerman, A.', 'Eckart, J. D.', 'Kenyon, R.', 'Will, R.', 'Setubal, J. C.', 'Sobral, B. W. S.']",Nucleic Acids Res,,,True
c62da850c36f3f10a1fa9289548460fa51b95f26,PMC,MMDB: annotating protein sequences with Entrez's 3D-structure database,http://dx.doi.org/10.1093/nar/gkl952,PMC1751549,17135201,CC BY-NC,"Three-dimensional (3D) structure is now known for a large fraction of all protein families. Thus, it has become rather likely that one will find a homolog with known 3D structure when searching a sequence database with an arbitrary query sequence. Depending on the extent of similarity, such neighbor relationships may allow one to infer biological function and to identify functional sites such as binding motifs or catalytic centers. Entrez's 3D-structure database, the Molecular Modeling Database (MMDB), provides easy access to the richness of 3D structure data and its large potential for functional annotation. Entrez's search engine offers several tools to assist biologist users: (i) links between databases, such as between protein sequences and structures, (ii) pre-computed sequence and structure neighbors, (iii) visualization of structure and sequence/structure alignment. Here, we describe an annotation service that combines some of these tools automatically, Entrez's ‘Related Structure’ links. For all proteins in Entrez, similar sequences with known 3D structure are detected by BLAST and alignments are recorded. The ‘Related Structure’ service summarizes this information and presents 3D views mapping sequence residues onto all 3D structures available in MMDB ().",2007 Jan 29,"['Wang, Yanli', 'Addess, Kenneth J.', 'Chen, Jie', 'Geer, Lewis Y.', 'He, Jane', 'He, Siqian', 'Lu, Shennan', 'Madej, Thomas', 'Marchler-Bauer, Aron', 'Thiessen, Paul A.', 'Zhang, Naigong', 'Bryant, Stephen H.']",Nucleic Acids Res,,,True
20f863c8fc0ff956ea9f902a2f9d1299ab8514a6,PMC,Genome Information Broker for Viruses (GIB-V): database for comparative analysis of virus genomes,http://dx.doi.org/10.1093/nar/gkl1004,PMC1781101,17158166,CC BY-NC,"Genome Information Broker for Viruses (GIB-V) is a comprehensive virus genome/segment database. We extracted 18 418 complete virus genomes/segments from the International Nucleotide Sequence Database Collaboration (INSDC, ) by DNA Data Bank of Japan (DDBJ), EMBL and GenBank and stored them in our system. The list of registered viruses is arranged hierarchically according to taxonomy. Keyword searches can be performed for genome/segment data or biological features of any virus stored in GIB-V. GIB-V is equipped with a BLAST search function, and search results are displayed graphically or in list form. Moreover, the BLAST results can be used online with the ClustalW feature of the DDBJ. All available virus genome/segment data can be collected by the GIB-V download function. GIB-V can be accessed at no charge at .",2007 Jan 7,"['Hirahata, Masaki', 'Abe, Takashi', 'Tanaka, Naoto', 'Kuwana, Yoshikazu', 'Shigemoto, Yasumasa', 'Miyazaki, Satoru', 'Suzuki, Yoshiyuki', 'Sugawara, Hideaki']",Nucleic Acids Res,,,True
2606e22c2560b4cc0909c102ee356d562d78a9f3,PMC,"Identification of functional, endogenous programmed −1 ribosomal frameshift signals in the genome of Saccharomyces cerevisiae",http://dx.doi.org/10.1093/nar/gkl1033,PMC1802563,17158156,CC BY-NC,"In viruses, programmed −1 ribosomal frameshifting (−1 PRF) signals direct the translation of alternative proteins from a single mRNA. Given that many basic regulatory mechanisms were first discovered in viral systems, the current study endeavored to: (i) identify −1 PRF signals in genomic databases, (ii) apply the protocol to the yeast genome and (iii) test selected candidates at the bench. Computational analyses revealed the presence of 10 340 consensus −1 PRF signals in the yeast genome. Of the 6353 yeast ORFs, 1275 contain at least one strong and statistically significant −1 PRF signal. Eight out of nine selected sequences promoted efficient levels of PRF in vivo. These findings provide a robust platform for high throughput computational and laboratory studies and demonstrate that functional −1 PRF signals are widespread in the genome of Saccharomyces cerevisiae. The data generated by this study have been deposited into a publicly available database called the PRFdb. The presence of stable mRNA pseudoknot structures in these −1 PRF signals, and the observation that the predicted outcomes of nearly all of these genomic frameshift signals would direct ribosomes to premature termination codons, suggest two possible mRNA destabilization pathways through which −1 PRF signals could post-transcriptionally regulate mRNA abundance.",2007 Jan 7,"['Jacobs, Jonathan L.', 'Belew, Ashton T.', 'Rakauskaite, Rasa', 'Dinman, Jonathan D.']",Nucleic Acids Res,,,True
b0a0f45be3069a32ba190502ab88b6df6d520199,PMC,Positional clustering improves computational binding site detection and identifies novel cis-regulatory sites in mammalian GABA(A) receptor subunit genes,http://dx.doi.org/10.1093/nar/gkl1062,PMC1807961,17204484,CC BY-NC,"Understanding transcription factor (TF) mediated control of gene expression remains a major challenge at the interface of computational and experimental biology. Computational techniques predicting TF-binding site specificity are frequently unreliable. On the other hand, comprehensive experimental validation is difficult and time consuming. We introduce a simple strategy that dramatically improves robustness and accuracy of computational binding site prediction. First, we evaluate the rate of recurrence of computational TFBS predictions by commonly used sampling procedures. We find that the vast majority of results are biologically meaningless. However clustering results based on nucleotide position improves predictive power. Additionally, we find that positional clustering increases robustness to long or imperfectly selected input sequences. Positional clustering can also be used as a mechanism to integrate results from multiple sampling approaches for improvements in accuracy over each one alone. Finally, we predict and validate regulatory sequences partially responsible for transcriptional control of the mammalian type A γ-aminobutyric acid receptor (GABA(A)R) subunit genes. Positional clustering is useful for improving computational binding site predictions, with potential application to improving our understanding of mammalian gene expression. In particular, predicted regulatory mechanisms in the mammalian GABA(A)R subunit gene family may open new avenues of research towards understanding this pharmacologically important neurotransmitter receptor system.",2007 Feb 3,"['Reddy, Timothy E.', 'Shakhnovich, Boris E.', 'Roberts, Daniel S.', 'Russek, Shelley J.', 'DeLisi, Charles']",Nucleic Acids Res,,,True
810e609cbc20ab7c1543f7131f18b7fd0a3e2ca8,PMC,Dual priming oligonucleotide system for the multiplex detection of respiratory viruses and SNP genotyping of CYP2C19 gene,http://dx.doi.org/10.1093/nar/gkm051,PMC1874606,17287288,CC BY-NC,"Successful PCR starts with proper priming between an oligonucleotide primer and the template DNA. However, the inevitable risk of mismatched priming cannot be avoided in the currently used primer system, even though considerable time and effort are devoted to primer design and optimization of reaction conditions. Here, we report a novel dual priming oligonucleotide (DPO) which contains two separate priming regions joined by a polydeoxyinosine linker. The linker assumes a bubble-like structure which itself is not involved in priming, but rather delineates the boundary between the two parts of the primer. This structure results in two primer segments with distinct annealing properties: a longer 5′-segment that initiates stable priming, and a short 3′-segment that determines target-specific extension. This DPO-based system is a fundamental tool for blocking extension of non-specifically primed templates, and thereby generates consistently high PCR specificity even under less than optimal PCR conditions. The strength and utility of the DPO system are demonstrated here using multiplex PCR and SNP genotyping PCR.",2007 Mar 7,"['Chun, Jong-Yoon', 'Kim, Kyoung-Joong', 'Hwang, In-Taek', 'Kim, Yun-Jee', 'Lee, Dae-Hoon', 'Lee, In-Kyoung', 'Kim, Jong-Kee']",Nucleic Acids Res,,,True
4b938c2f60ce863541ac9ca19fe0a98cd9a8730e,PMC,Selective redox regulation of cytokine receptor signaling by extracellular thioredoxin-1,http://dx.doi.org/10.1038/sj.emboj.7601746,PMC1914094,17557078,CC BY-NC-ND,"The thiol-disulfide oxidoreductase thioredoxin-1 (Trx1) is known to be secreted by leukocytes and to exhibit cytokine-like properties. Extracellular effects of Trx1 require a functional active site, suggesting a redox-based mechanism of action. However, specific cell surface proteins and pathways coupling extracellular Trx1 redox activity to cellular responses have not been identified so far. Using a mechanism-based kinetic trapping technique to identify disulfide exchange interactions on the intact surface of living lymphocytes, we found that Trx1 catalytically interacts with a single principal target protein. This target protein was identified as the tumor necrosis factor receptor superfamily member 8 (TNFRSF8/CD30). We demonstrate that the redox interaction is highly specific for both Trx1 and CD30 and that the redox state of CD30 determines its ability to engage the cognate ligand and transduce signals. Furthermore, we confirm that Trx1 affects CD30-dependent changes in lymphocyte effector function. Thus, we conclude that receptor–ligand signaling interactions can be selectively regulated by an extracellular redox catalyst.",2007 Jul 11,"['Schwertassek, Ulla', 'Balmer, Yves', 'Gutscher, Marcus', 'Weingarten, Lars', 'Preuss, Marc', 'Engelhard, Johanna', 'Winkler, Monique', 'Dick, Tobias P']",EMBO J,,,True
163ed638c72f8fa3b0637416fbe5084c41c7baab,PMC,Selective redox regulation of cytokine receptor signaling by extracellular thioredoxin-1,http://dx.doi.org/10.1038/sj.emboj.7601746,PMC1914094,17557078,CC BY-NC-ND,"The thiol-disulfide oxidoreductase thioredoxin-1 (Trx1) is known to be secreted by leukocytes and to exhibit cytokine-like properties. Extracellular effects of Trx1 require a functional active site, suggesting a redox-based mechanism of action. However, specific cell surface proteins and pathways coupling extracellular Trx1 redox activity to cellular responses have not been identified so far. Using a mechanism-based kinetic trapping technique to identify disulfide exchange interactions on the intact surface of living lymphocytes, we found that Trx1 catalytically interacts with a single principal target protein. This target protein was identified as the tumor necrosis factor receptor superfamily member 8 (TNFRSF8/CD30). We demonstrate that the redox interaction is highly specific for both Trx1 and CD30 and that the redox state of CD30 determines its ability to engage the cognate ligand and transduce signals. Furthermore, we confirm that Trx1 affects CD30-dependent changes in lymphocyte effector function. Thus, we conclude that receptor–ligand signaling interactions can be selectively regulated by an extracellular redox catalyst.",2007 Jul 11,"['Schwertassek, Ulla', 'Balmer, Yves', 'Gutscher, Marcus', 'Weingarten, Lars', 'Preuss, Marc', 'Engelhard, Johanna', 'Winkler, Monique', 'Dick, Tobias P']",EMBO J,,,False
281b4272005dbc998e36b034b7fb528c9ba038cd,PMC,s-RT-MELT for rapid mutation scanning using enzymatic selection and real time DNA-melting: new potential for multiplex genetic analysis,http://dx.doi.org/10.1093/nar/gkm403,PMC1919510,17545195,CC BY-NC,"The rapidly growing understanding of human genetic pathways, including those that mediate cancer biology and drug response, leads to an increasing need for extensive and reliable mutation screening on a population or on a single patient basis. Here we describe s-RT-MELT, a novel technology that enables highly expanded enzymatic mutation scanning in human samples for germline or low-level somatic mutations, or for SNP discovery. GC-clamp-containing PCR products from interrogated and wild-type samples are hybridized to generate mismatches at the positions of mutations over one or multiple sequences in-parallel. Mismatches are converted to double-strand breaks using a DNA endonuclease (Surveyor™) and oligonucleotide tails are enzymatically attached at the position of mutations. A novel application of PCR enables selective amplification of mutation-containing DNA fragments. Subsequently, melting curve analysis, on conventional or nano-technology real-time PCR platforms, detects the samples that contain mutations in a high-throughput and closed-tube manner. We apply s-RT-MELT in the screening of p53 and EGFR mutations in cell lines and clinical samples and demonstrate its advantages for rapid, multiplexed mutation scanning in cancer and for genetic variation screening in biology and medicine.",2007 Jun 1,"['Li, Jin', 'Berbeco, Ross', 'Distel, Robert J.', 'Jänne, Pasi A.', 'Wang, Lilin', 'Makrigiorgos, G. Mike']",Nucleic Acids Res,,,True
f3bb0e1694f0ef38fa9cfd386aed18174d0b6b58,PMC,s-RT-MELT for rapid mutation scanning using enzymatic selection and real time DNA-melting: new potential for multiplex genetic analysis,http://dx.doi.org/10.1093/nar/gkm403,PMC1919510,17545195,CC BY-NC,"The rapidly growing understanding of human genetic pathways, including those that mediate cancer biology and drug response, leads to an increasing need for extensive and reliable mutation screening on a population or on a single patient basis. Here we describe s-RT-MELT, a novel technology that enables highly expanded enzymatic mutation scanning in human samples for germline or low-level somatic mutations, or for SNP discovery. GC-clamp-containing PCR products from interrogated and wild-type samples are hybridized to generate mismatches at the positions of mutations over one or multiple sequences in-parallel. Mismatches are converted to double-strand breaks using a DNA endonuclease (Surveyor™) and oligonucleotide tails are enzymatically attached at the position of mutations. A novel application of PCR enables selective amplification of mutation-containing DNA fragments. Subsequently, melting curve analysis, on conventional or nano-technology real-time PCR platforms, detects the samples that contain mutations in a high-throughput and closed-tube manner. We apply s-RT-MELT in the screening of p53 and EGFR mutations in cell lines and clinical samples and demonstrate its advantages for rapid, multiplexed mutation scanning in cancer and for genetic variation screening in biology and medicine.",2007 Jun 1,"['Li, Jin', 'Berbeco, Ross', 'Distel, Robert J.', 'Jänne, Pasi A.', 'Wang, Lilin', 'Makrigiorgos, G. Mike']",Nucleic Acids Res,,,False
6f7b39ecfc90c29ae92f607ebe37c55a1d4f575d,PMC,s-RT-MELT for rapid mutation scanning using enzymatic selection and real time DNA-melting: new potential for multiplex genetic analysis,http://dx.doi.org/10.1093/nar/gkm403,PMC1919510,17545195,CC BY-NC,"The rapidly growing understanding of human genetic pathways, including those that mediate cancer biology and drug response, leads to an increasing need for extensive and reliable mutation screening on a population or on a single patient basis. Here we describe s-RT-MELT, a novel technology that enables highly expanded enzymatic mutation scanning in human samples for germline or low-level somatic mutations, or for SNP discovery. GC-clamp-containing PCR products from interrogated and wild-type samples are hybridized to generate mismatches at the positions of mutations over one or multiple sequences in-parallel. Mismatches are converted to double-strand breaks using a DNA endonuclease (Surveyor™) and oligonucleotide tails are enzymatically attached at the position of mutations. A novel application of PCR enables selective amplification of mutation-containing DNA fragments. Subsequently, melting curve analysis, on conventional or nano-technology real-time PCR platforms, detects the samples that contain mutations in a high-throughput and closed-tube manner. We apply s-RT-MELT in the screening of p53 and EGFR mutations in cell lines and clinical samples and demonstrate its advantages for rapid, multiplexed mutation scanning in cancer and for genetic variation screening in biology and medicine.",2007 Jun 1,"['Li, Jin', 'Berbeco, Ross', 'Distel, Robert J.', 'Jänne, Pasi A.', 'Wang, Lilin', 'Makrigiorgos, G. Mike']",Nucleic Acids Res,,,False
71483655659aa67d782f72923d0e1dff006c7319,PMC,s-RT-MELT for rapid mutation scanning using enzymatic selection and real time DNA-melting: new potential for multiplex genetic analysis,http://dx.doi.org/10.1093/nar/gkm403,PMC1919510,17545195,CC BY-NC,"The rapidly growing understanding of human genetic pathways, including those that mediate cancer biology and drug response, leads to an increasing need for extensive and reliable mutation screening on a population or on a single patient basis. Here we describe s-RT-MELT, a novel technology that enables highly expanded enzymatic mutation scanning in human samples for germline or low-level somatic mutations, or for SNP discovery. GC-clamp-containing PCR products from interrogated and wild-type samples are hybridized to generate mismatches at the positions of mutations over one or multiple sequences in-parallel. Mismatches are converted to double-strand breaks using a DNA endonuclease (Surveyor™) and oligonucleotide tails are enzymatically attached at the position of mutations. A novel application of PCR enables selective amplification of mutation-containing DNA fragments. Subsequently, melting curve analysis, on conventional or nano-technology real-time PCR platforms, detects the samples that contain mutations in a high-throughput and closed-tube manner. We apply s-RT-MELT in the screening of p53 and EGFR mutations in cell lines and clinical samples and demonstrate its advantages for rapid, multiplexed mutation scanning in cancer and for genetic variation screening in biology and medicine.",2007 Jun 1,"['Li, Jin', 'Berbeco, Ross', 'Distel, Robert J.', 'Jänne, Pasi A.', 'Wang, Lilin', 'Makrigiorgos, G. Mike']",Nucleic Acids Res,,,False
143381fcb7566228ad053f619d03efdfbc2668b3,PMC,RE-MuSiC: a tool for multiple sequence alignment with regular expression constraints,http://dx.doi.org/10.1093/nar/gkm275,PMC1933182,17488842,CC BY-NC,"RE-MuSiC is a web-based multiple sequence alignment tool that can incorporate biological knowledge about structure, function, or conserved patterns regarding the sequences of interest. It accepts amino acid or nucleic acid sequences and a set of constraints as inputs. The constraints are pattern descriptions, instead of exact positions of fragments to be aligned together. The output is an alignment where for each pattern (constraint), an occurrence on each sequence can be found aligned together with those on the other sequences, in a manner that the overall alignment is optimized. Its predecessor, MuSiC, has been found useful by researchers since its release in 2004. However, it is noticed in applications that the pattern formulation adopted in MuSiC, namely, plain strings allowing mismatches, is not expressive and flexible enough. The constraint formulation adopted in RE-MuSiC is therefore enhanced to be regular expressions, which is convenient in expressing many biologically significant patterns like those collected in the PROSITE database, or structural consensuses that often involve variable ranges between conserved parts. Experiments demonstrate that RE-MuSiC can be used to help predict important residues and locate phylogenetically conserved structural elements. RE-MuSiC is available on-line at http://140.113.239.131/RE-MUSIC.",2007 Jul 8,"['Chung, Yun-Sheng', 'Lee, Wei-Hsun', 'Tang, Chuan Yi', 'Lu, Chin Lung']",Nucleic Acids Res,,,True
6d53690848c0b900e6d766993d9fefd2c4c27c48,PMC,pknotsRG: RNA pseudoknot folding including near-optimal structures and sliding windows,http://dx.doi.org/10.1093/nar/gkm258,PMC1933184,17478505,CC BY-NC,"RNA pseudoknots are an important structural feature of RNAs, but often neglected in computer predictions for reasons of efficiency. Here, we present the pknotsRG Web Server for single sequence RNA secondary structure prediction including pseudoknots. pknotsRG employs the newest Turner energy rules for finding the structure of minimal free energy. The algorithm has been improved in several ways recently. First, it has been reimplemented in the C programming language, resulting in a 60-fold increase in speed. Second, all suboptimal foldings up to a user-defined threshold can be enumerated. For large scale analysis, a fast sliding window mode is available. Further improvements of the Web Server are a new output visualization using the PseudoViewer Web Service or RNAmovies for a movie like animation of several suboptimal foldings. The tool is available as source code, binary executable, online tool or as Web Service. The latter alternative allows for an easy integration into bio-informatics pipelines. pknotsRG is available at the Bielefeld Bioinformatics Server (http://bibiserv.techfak.uni-bielefeld.de/pknotsrg).",2007 Jul 3,"['Reeder, Jens', 'Steffen, Peter', 'Giegerich, Robert']",Nucleic Acids Res,,,True
b07181f9086788a6a4f7de90129118352320e993,PMC,Miniaturized PCR chips for nucleic acid amplification and analysis: latest advances and future trends,http://dx.doi.org/10.1093/nar/gkm389,PMC1934988,17576684,CC BY-NC,"The possibility of performing fast and small-volume nucleic acid amplification and analysis on a single chip has attracted great interest. Devices based on this idea, referred to as micro total analysis, microfluidic analysis, or simply ‘Lab on a chip’ systems, have witnessed steady advances over the last several years. Here, we summarize recent research on chip substrates, surface treatments, PCR reaction volume and speed, architecture, approaches to eliminating cross-contamination and control and measurement of temperature and liquid flow. We also discuss product-detection methods, integration of functional components, biological samples used in PCR chips, potential applications and other practical issues related to implementation of lab-on-a-chip technologies.",2007 Jul 18,"['Zhang, Chunsun', 'Xing, Da']",Nucleic Acids Res,,,True
d429ec26fa0c9d7bcb427bd485a6ae042add26cc,PMC,Cell-penetrating peptides as transporters for morpholino oligomers: effects of amino acid composition on intracellular delivery and cytotoxicity,http://dx.doi.org/10.1093/nar/gkm478,PMC1976451,17670797,CC BY-NC,"Arginine-rich cell-penetrating peptides (CPPs) are promising transporters for intracellular delivery of antisense morpholino oligomers (PMO). Here, we determined the effect of L-arginine, D-arginine and non-α amino acids on cellular uptake, splice-correction activity, cellular toxicity and serum binding for 24 CPP−PMOs. Insertion of 6-aminohexanoic acid (X) or β-alanine (B) residues into oligoarginine R(8) decreased the cellular uptake but increased the splice-correction activity of the resulting compound, with a greater increase for the sequences containing more X residues. Cellular toxicity was not observed for any of the conjugates up to 10 μM. Up to 60 μM, only the conjugates with ⩾ 5 Xs exhibited time- and concentration-dependent toxicity. Substitution of L-arginine with D-arginine did not increase uptake or splice-correction activity. High concentration of serum significantly decreased the uptake and splice-correction activity of oligoarginine conjugates, but had much less effect on the conjugates containing X or B. In summary, incorporation of X/B into oligoarginine enhanced the antisense activity and serum-binding profile of CPP−PMO. Toxicity of X/B-containing conjugates was affected by the number of Xs, treatment time and concentration. More active, stable and less toxic CPPs can be designed by optimizing the position and number of R, D-R, X and B residues.",2007 Aug 1,"['Wu, Rebecca P.', 'Youngblood, Derek S.', 'Hassinger, Jed N.', 'Lovejoy, Candace E.', 'Nelson, Michelle H.', 'Iversen, Patrick L.', 'Moulton, Hong M.']",Nucleic Acids Res,,,True
6ff8826ca04c185f3a88ab4b0d5a912aea4ab1a6,PMC,Electrospray ionisation-cleavable tandem nucleic acid mass tag–peptide nucleic acid conjugates: synthesis and applications to quantitative genomic analysis using electrospray ionisation-MS/MS,http://dx.doi.org/10.1093/nar/gkl1123,PMC1994780,17259215,CC BY-NC,"The synthesis and characterization of isotopomer tandem nucleic acid mass tag–peptide nucleic acid (TNT–PNA) conjugates is described along with their use as electrospray ionisation-cleavable (ESI-Cleavable) hybridization probes for the detection and quantification of target DNA sequences by electrospray ionisation tandem mass spectrometry (ESI-MS/MS). ESI-cleavable peptide TNT isotopomers were introduced into PNA oligonucleotide sequences in a total synthesis approach. These conjugates were evaluated as hybridization probes for the detection and quantification of immobilized synthetic target DNAs using ESI-MS/MS. In these experiments, the PNA portion of the conjugate acts as a hybridization probe, whereas the peptide TNT is released in a collision-based process during the ionization of the probe conjugate in the electrospray ion source. The cleaved TNT acts as a uniquely resolvable marker to identify and quantify a unique target DNA sequence. The method should be applicable to a wide variety of assays requiring highly multiplexed, quantitative DNA/RNA analysis, including gene expression monitoring, genetic profiling and the detection of pathogens.",2007 Feb 26,"['Thompson, Andrew', 'Prescott, Mark', 'Chelebi, Noorhan', 'Smith, John', 'Brown, Tom', 'Schmidt, Günter']",Nucleic Acids Res,,,True
ac8fb04ef901727de6945ff40313cd94423d1da3,PMC,Thirty Years into the Genomics Era: Tumor Viruses Led the Way,,PMC1994808,17940630,CC BY-NC,,2006 Dec,"['DiMaio, Daniel', 'Miller, George']",Yale J Biol Med,,,True
6a3c7595bc8fa30e3f74fd3d350d7cb7e3a1668b,PMC,"The three transfer RNAs occupying the A, P and E sites on the ribosome are involved in viral programmed -1 ribosomal frameshift",http://dx.doi.org/10.1093/nar/gkm578,PMC2018615,17704133,CC BY-NC,"The -1 programmed ribosomal frameshifts (PRF), which are used by many viruses, occur at a heptanucleotide slippery sequence and are currently thought to involve the tRNAs interacting with the ribosomal P- and A-site codons. We investigated here whether the tRNA occupying the ribosomal E site that precedes a slippery site influences -1 PRF. Using the human immunodeficiency virus type 1 (HIV-1) frameshift region, we found that mutating the E-site codon altered the -1 PRF efficiency. When the HIV-1 slippery sequence was replaced with other viral slippery sequences, mutating the E-site codon also altered the -1 PRF efficiency. Because HIV-1 -1 PRF can be recapitulated in bacteria, we used a bacterial ribosome system to select, by random mutagenesis, 16S ribosomal RNA (rRNA) mutations that modify the expression of a reporter requiring HIV-1 -1 PRF. Three mutants were isolated, which are located in helices 21 and 22 of 16S rRNA, a region involved in translocation and E-site tRNA binding. We propose a novel model where -1 PRF is triggered by an incomplete translocation and depends not only on the tRNAs interacting with the P- and A-site codons, but also on the tRNA occupying the E site.",2007 Aug 17,"['Léger, Mélissa', 'Dulude, Dominic', 'Steinberg, Sergey V.', 'Brakier-Gingras, Léa']",Nucleic Acids Res,,,True
e3dd1ad4bb9542f0f8fc13f5faab78ee531ae89b,PMC,Hairpin structure within the 3′UTR of DNA polymerase β mRNA acts as a post-transcriptional regulatory element and interacts with Hax-1,http://dx.doi.org/10.1093/nar/gkm502,PMC2018635,17704138,CC BY-NC,"Aberrant expression of DNA polymerase β, a key enzyme involved in base excision repair, leads to genetic instability and carcinogenesis. Pol β expression has been previously shown to be regulated at the level of transcription, but there is also evidence of post-transcriptional regulation, since rat transcripts undergo alternative polyadenylation, and the resulting 3′UTR contain at least one regulatory element. Data presented here indicate that RNA of the short 3′UTR folds to form a strong secondary structure (hairpin). Its regulatory role was established utilizing a luciferase-based reporter system. Further studies led to the identification of a protein factor, which binds to this element—the anti-apoptotic, cytoskeleton-related protein Hax-1. The results of in vitro binding analysis indicate that the formation of the RNA–protein complex is significantly impaired by disruption of the hairpin motif. We demonstrate that Hax-1 binds to Pol β mRNA exclusively in the form of a dimer. Biochemical analysis revealed the presence of Hax-1 in mitochondria, but also in the nuclear matrix, which, along with its transcript-binding properties, suggests that Hax-1 plays a role in post-transcriptional regulation of expression of Pol β.",2007 Aug 17,"['Sarnowska, Elżbieta', 'Grzybowska, Ewa A.', 'Sobczak, Krzysztof', 'Konopiński, Ryszard', 'Wilczyńska, Anna', 'Szwarc, Maria', 'Sarnowski, Tomasz J.', 'Krzyżosiak, Włodzimierz J.', 'Siedlecki, Janusz A.']",Nucleic Acids Res,,,True
616d2117cb63fecdaa5ae2901cca9d1b610dd799,PMC,AN ELECTRON MICROSCOPE STUDY OF THE DEVELOPMENT OF A MOUSE HEPATITIS VIRUS IN TISSUE CULTURE CELLS,,PMC2106561,14286297,CC BY-NC-SA,"Samples taken at different intervals of time from suspension cultures of the NCTC 1469 line of mouse liver—derived (ML) cells infected with a mouse hepatitis virus have been studied with the electron microscope. The experiments revealed that the viruses are incorporated into the cells by viropexis within 1 hour after being added to the culture. An increasing number of particles are found later inside dense cytoplasmic corpuscles similar to lysosomes. In the cytoplasm of the cells from the samples taken 7 hours after inoculation, two organized structures generally associated and never seen in the controls are observed: one consists of dense material arranged in a reticular disposition (reticular inclusion); the other is formed by small tubules organized in a complex pattern (tubular body). No evidence has been found concerning their origin. Their significance is discussed. With the progression of the infection a system of membrane-bounded tubules and cisternae is differentiated in the cytoplasm of the ML cells. In the lumen of these tubules or cisternae, which are occupied by a dense material, numerous virus particles are observed. The virus particles which originate in association with the limiting membranes of tubules and cisternae are released into their lumen by a ""budding"" process. The virus particles are 75 mµ in diameter and possess a nucleoid constituted of dense particles or rods limiting an electron transparent core. The virus limiting membrane is sometimes covered by an outer layer of a dense material. In the cells from the samples taken 14 to 20 hours after inoculation, larger zones of the cell cytoplasm are occupied by inclusion bodies formed by channels or cisternae with their lumens containing numerous virus particles. In the samples taken 20 hours or more after the inoculation numerous cells show evident signs of degeneration.",1965 Jan 1,"['David-Ferreira, J. F.', 'Manaker, R. A.']",J Cell Biol,,,True
1a3ac4ed56c42714b04e97e0e5e11a93c5a91508,PMC,Biosynthesis and processing of ribophorins in the endoplasmic reticulum,,PMC2113407,6470038,CC BY-NC-SA,"Ribophorins are two transmembrane glycoproteins characteristic of the rough endoplasmic reticulum, which are thought to be involved in the binding of ribosomes. Their biosynthesis was studied in vivo using lines of cultured rat hepatocytes (clone 9) and pituitary cells (GH 3.1) and in cell-free synthesis experiments. In vitro translation of mRNA extracted from free and bound polysomes of clone 9 cells demonstrated that ribophorins are made exclusively on bound polysomes. The primary translation products of ribophorin messengers obtained from cultured hepatocytes or from regenerating livers co-migrated with the respective mature proteins, but had slightly higher apparent molecular weights (2,000) than the unglycosylated forms immunoprecipitated from cells treated with tunicamycin. This indicates that ribophorins, in contrast to all other endoplasmic reticulum membrane proteins previously studied, contain transient amino-terminal insertion signals which are removed co-translationally. Kinetic and pulse-chase experiments with [35S]methionine and [3H]mannose demonstrated that ribophorins are not subjected to electrophoretically detectable posttranslational modifications, such as proteolytic cleavage or trimming and terminal glycosylation of oligosaccharide side chain(s). Direct analysis of the oligosaccharides of ribophorin l showed that they do not contain the terminal sugars characteristic of complex oligosaccharides and that they range in composition from Man8GlcNAc to Man5GlcNAc. These findings, as well as the observation that the mature proteins are sensitive to endoglycosidase H and insensitive to endoglycosidase D, are consistent with the notion that the biosynthetic pathway of the ribophorins does not require a stage of passage through the Golgi apparatus.",1984 Sep 1,,J Cell Biol,,,True
e2e23d6985639b6aa9671a1006fe80a41abded5c,PMC,Specific asparagine-linked oligosaccharides are not required for certain neuron-neuron and neuron-Schwann cell interactions,,PMC2113797,3522602,CC BY-NC-SA,"To determine whether specific asparagine-linked (N-linked) oligosaccharides present in cell surface glycoproteins are required for cell-cell interactions within the peripheral nervous system, we have used castanospermine to inhibit maturation of N-linked sugars in cell cultures of neurons or neurons plus Schwann cells. Maximally 10-15% of the N-linked oligosaccharides on neuronal proteins have normal structure when cells are cultured in the presence of 250 micrograms/ml castanospermine; the remaining oligosaccharides are present as immature carbohydrate chains not normally found in these glycoproteins. Although cultures were treated for 2 wk with castanospermine, cells always remained viable and appeared healthy. We have analyzed several biological responses of embryonic dorsal root ganglion neurons, with or without added purified populations of Schwann cells, in the presence of castanospermine. We have observed that a normal complement of mature, N- linked sugars are not required for neurite outgrowth, neuron-Schwann cell adhesion, neuron-induced Schwann cell proliferation, or ensheathment of neurites by Schwann cells. Treatment of neuronal cultures with castanospermine increases the propensity of neurites to fasciculate. Extracellular matrix deposition by Schwann cells and myelination of neurons by Schwann cells are greatly diminished in the presence of castanospermine as assayed by electron microscopy and immunocytochemistry, suggesting that specific N-linked oligosaccharides are required for the expression of these cellular functions.",1986 Jul 1,,J Cell Biol,,,True
8f4348a9455035db6487252e4fb48c65708a1e1f,PMC,Biochemical studies on cell fusion. II. Control of fusion response by lipid alteration,,PMC2113917,4044646,CC BY-NC-SA,"The preceding communication (Roos, D.S. and P.W. Choppin, 1985, J. Cell Biol. 101:1578-1590) described the lipid composition of a series of mouse fibroblast cell lines which vary in susceptibility to the fusogenic effects of polyethylene glycol (PEG). Two alterations in lipid content were found to be directly correlated with resistance to PEG-induced cell fusion: increases in fatty acyl chain saturation, and the elevation of neutral glycerides, including an unusual ether-linked compound. In this study, we have probed the association between lipid composition and cell fusion through the use of fatty acid supplements to the cellular growth medium, and show that the fusibility of cells can be controlled by altering their acyl chain composition. The parental Clone 1D cells contain moderately unsaturated fatty acids with a ratio of saturates to polyunsaturates (S/P) approximately 1 and fuse virtually to completion following a standard PEG treatment. By contrast, the lipids of a highly fusion-resistant mutant cell line, F40, are highly saturated (S/P approximately 4). When the S/P ratio of Clone 1D cells was increased to approximate that normally found in F40 cells by growth in the presence of high concentrations of saturated fatty acids, they became highly resistant to PEG. Reduction of the S/P ratio of F40 cells by growth in cis-polyunsaturated fatty acids rendered them susceptible to fusion. Cell lines F8, F16, etc., which are normally intermediate between Clone 1D and F40 in both lipid composition and fusion response, can be altered in either direction (towards either increased or decreased susceptibility to fusion) by the addition of appropriate fatty acids to the growth medium. Although trans-unsaturated fatty acids have phase-transition temperatures roughly similar to saturated compounds, and might therefore be expected to affect membrane fluidity in a similar manner, trans-unsaturated fatty acids exerted the same effect as cis-unsaturates on the control of PEG-induced cell fusion. This observation suggests that the control of cell fusion by alteration of fatty acid content is not due to changes in membrane fluidity, and thus that the fatty acids are involved in some other way in the modulation of cell fusion.",1985 Oct 1,,J Cell Biol,,,True
c838ca724d9916867c83ad89c823ca61027bd046,PMC,"Deletions into an NH2-terminal hydrophobic domain result in secretion of rotavirus VP7, a resident endoplasmic reticulum membrane glycoprotein",,PMC2113985,2999159,CC BY-NC-SA,"Rotavirus, a non-enveloped reovirus, buds into the rough endoplasmic reticulum and transiently acquires a membrane. The structural glycoprotein, VP7, a 38-kD integral membrane protein of the endoplasmic reticulum (ER), presumably transfers to virus in this process. The gene for VP7 potentially encodes a protein of 326 amino acids which has two tandem hydrophobic domains at the NH2-terminal, each preceded by an in- frame ATG codon. A series of deletion mutants constructed from a full- length cDNA clone of the Simian 11 rotavirus VP7 gene were expressed in COS 7 cells. Products from wild-type, and mutants which did not affect the second hydrophobic domain of VP7, were localized by immunofluorescence to elements of the ER only. However, deletions affecting the second hydrophobic domain (mutants 42-61, 43-61, 47-61) showed immunofluorescent localization of VP7 which coincided with that of wheat germ agglutinin, indicating transport to the Golgi apparatus. Immunoprecipitable wild-type protein, or an altered protein lacking the first hydrophobic sequence, remained intracellular and endo-beta-N- acetylglucosaminidase H sensitive. In contrast, products of mutants 42- 61, 43-61, and 47-61 were transported from the ER, and secreted. Glycosylation of the secreted molecules was inhibited by tunicamycin, resistant to endo-beta-N-acetylglucosaminidase H digestion and therefore of the N-linked complex type. An unglycosylated version of VP7 was also secreted. We suggest that the second hydrophobic domain contributes to a positive signal for ER location and a membrane anchor function. Secretion of the mutant glycoprotein implies that transport can be constitutive with the destination being dictated by an overriding compartmentalization signal.",1985 Dec 1,,J Cell Biol,,,True
6328beb961554b05276359e9c5b26d2e57cd52e9,PMC,Cytoplasmic domains of cellular and viral integral membrane proteins substitute for the cytoplasmic domain of the vesicular stomatitis virus glycoprotein in transport to the plasma membrane,,PMC2114239,3011809,CC BY-NC-SA,"Oligonucleotide-directed mutagenesis was used to construct chimeric cDNAs that encode the extracellular and transmembrane domains of the vesicular stomatitis virus glycoprotein (G) linked to the cytoplasmic domain of either the immunoglobulin mu membrane heavy chain, the hemagglutinin glycoprotein of influenza virus, or the small glycoprotein (p23) of infectious bronchitis virus. Biochemical analyses and immunofluorescence microscopy demonstrated that these hybrid genes were correctly expressed in eukaryotic cells and that the hybrid proteins were transported to the plasma membrane. The rate of transport to the Golgi complex of G protein with an immunoglobulin mu membrane cytoplasmic domain was approximately sixfold slower than G protein with its normal cytoplasmic domain. However, this rate was virtually identical to the rate of transport of micron heavy chain molecules measured in the B cell line WEHI 231. The rate of transport of G protein with a hemagglutinin cytoplasmic domain was threefold slower than wild type G protein and G protein with a p23 cytoplasmic domain, which were transported at similar rates. The combined results underscore the importance of the amino acid sequence in the cytoplasmic domain for efficient transport of G protein to the cell surface. Also, normal cytoplasmic domains from other transmembrane glycoproteins can substitute for the G protein cytoplasmic domain in transport of G protein to the plasma membrane. The method of constructing precise hybrid proteins described here will be useful in defining functions of specific domains of viral and cellular integral membrane proteins.",1986 Jun 1,,J Cell Biol,,,True
67f40427adfd7f712e114a8f5da4a33158fc9f37,PMC,Signal recognition particle-dependent membrane insertion of mouse invariant chain: a membrane-spanning protein with a cytoplasmically exposed amino terminus,,PMC2114261,3458708,CC BY-NC-SA,"Invariant (Ii) chain is a membrane-spanning protein that is found associated intracellularly with class II histocompatibility antigens. In the endoplasmic reticulum Ii chain spans the membrane and exposes the NH2 terminus on the cytoplasmic and the COOH terminus on the lumenal side. This orientation across the membrane is demonstrated directly with the monoclonal antibody In-1, which exclusively recognizes the NH2 terminal cytoplasmically exposed part of Ii chain. Membrane insertion of Ii chain requires signal recognition particle and docking protein. When tested in a wheat germ cell free system, signal recognition particle arrests translation of Ii chain. No signal sequence is cleaved from Ii chain upon membrane insertion.",1986 Jun 1,,J Cell Biol,,,True
f1b5cde5a242e912703bae5311866136ef780c9d,PMC,Sorting of progeny coronavirus from condensed secretory proteins at the exit from the trans-Golgi network of AtT20 cells,,PMC2114808,2821011,CC BY-NC-SA,"Murine hepatitis virus (strain A59), (MHV-A59) is a coronavirus that buds into pre-Golgi compartments and then exploits the exocytic pathway of the host cell to reach the exterior. The fibroblastic cells in which replication of this virus is usually studied have only a constitutive exocytic pathway that the virus uses. MHV-A59 also infects, albeit inefficiently, AtT20 cells, murine pituitary tumor cells with a regulated as well as a constitutive exocytic pathway. Here we examine AtT20 cells at early times after the infection, when the Golgi apparatus retains its morphological and biochemical integrity. We observe that progeny coronavirus and secretory protein destined for the secretory granules of the regulated exocytic pathway traverse the same Golgi stacks and accumulate in the trans-Golgi network. Their pathways diverge at this site, the condensed secretory proteins including the ACTH going to the secretory granules and the coronavirus to post-Golgi transport vesicles devoid of ACTH. On very rare occasions there is missorting such that aggregates of condensed secretory proteins and viruses occur together in post-Golgi vesicles. We conclude that the constitutive and regulated exocytic pathways, identified respectively by the progeny virions and the secretory protein ACTH, diverge at the exit from the trans-Golgi network.",1987 Sep 1,,J Cell Biol,,,True
3ac5e3619d6decbe8deedc18bb939bbfbf0c707c,PMC,A specific transmembrane domain of a coronavirus E1 glycoprotein is required for its retention in the Golgi region,,PMC2114809,2821010,CC BY-NC-SA,"The E1 glycoprotein of the avian coronavirus infectious bronchitis virus contains a short, glycosylated amino-terminal domain, three membrane-spanning domains, and a long carboxy-terminal cytoplasmic domain. We show that E1 expressed from cDNA is targeted to the Golgi region, as it is in infected cells. E1 proteins with precise deletions of the first and second or the second and third membrane-spanning domains were glycosylated, thus suggesting that either the first or third transmembrane domain can function as an internal signal sequence. The mutant protein with only the first transmembrane domain accumulated intracellularly like the wild-type protein, but the mutant protein with only the third transmembrane domain was transported to the cell surface. This result suggests that information specifying accumulation in the Golgi region resides in the first transmembrane domain, and provides the first example of an intracellular membrane protein that is transported to the plasma membrane after deletion of a specific domain.",1987 Sep 1,,J Cell Biol,,,True
bbccfb72296dcfb544b20996414b7b70622214da,PMC,Site of addition of N-acetyl-galactosamine to the E1 glycoprotein of mouse hepatitis virus-A59,,PMC2115043,2836431,CC BY-NC-SA,"By pulse-chase labeling with [35S]methionine and long-term labeling with 3H-sugars, the E1 glycoprotein of coronavirus MHV-A59 has been shown to acquire O-linked oligosaccharides in a two-step process. About 10 min after synthesis of the E1 protein, N-acetyl-galactosamine was added. This was followed approximately 10 min later by the addition of both galactose and sialic acid to give the mature oligosaccharides. This sequence of additions was confirmed by analyzing the 3H-labeled oligosaccharides bound to each of the E1 forms using gel filtration on P4 columns. The intracellular location of the first step was determined by exploiting the temperature sensitivity of virus release. The virus normally buds first into a smooth membrane compartment lying between the rough endoplasmic reticulum and the cis side of the Golgi stack (Tooze et al., 1984). At 31 degrees C the virus is assembled but does not appear to enter the Golgi stacks. The addition of N-acetyl- galactosamine is unaffected although the addition of galactose and sialic acid is inhibited. These results strongly suggest that addition of N-acetyl-galactosamine occurs in this budding compartment, the morphology of which is similar to that of transitional elements and vesicles.",1988 May 1,,J Cell Biol,,,True
d256d493f1987779fa7f2b417941d497bed6b878,PMC,Integration of membrane proteins into the endoplasmic reticulum requires GTP,,PMC2115162,2839521,CC BY-NC-SA,"We have examined the requirement for ribonucleotides and ribonucleotide triphosphate hydrolysis during early events in the membrane integration of two membrane proteins: the G protein of vesicular stomatitis virus and the hemagglutinin-neuraminidase (HN) glycoprotein of Newcastle disease virus. Both proteins contain a single transmembrane-spanning segment but are integrated in the membrane with opposite orientations. The G protein has an amino-terminal signal sequence and a stop-transfer sequence located near the carboxy terminus. The HN glycoprotein has a single sequence near the amino terminus that functions as both a signal- sequence and a transmembrane-spanning segment. Membrane insertion was explored using a cell-free system directed by transcribed mRNAs encoding amino-terminal segments of the two proteins. Ribosome-bound nascent polypeptides were assembled, ribonucleotides were removed by gel filtration chromatography, and the ribosomes were incubated with microsomal membranes under conditions of defined ribonucleotide content. Nascent chain insertion into the membrane required the presence of both the signal recognition particle and a functional signal recognition particle receptor. In the absence of ribonucleotides, insertion of nascent membrane proteins was not detected. GTP or nonhydrolyzable GTP analogues promoted efficient insertion, while ATP was comparatively ineffective. Surprisingly, the majority of the HN nascent chain remained ribosome associated after puromycin treatment. Ribosome-associated HN nascent chains remained competent for membrane insertion, while free HN chains were not competent. We conclude that a GTP binding protein performs an essential function during ribosome-dependent insertion of membrane proteins into the endoplasmic reticulum that is unrelated to protein synthesis.",1988 Jul 1,,J Cell Biol,,,True
26b49bdf0c3d50386ae603783e9674b7349852df,PMC,Primary sequence domains required for the retention of rotavirus VP7 in the endoplasmic reticulum,,PMC2115309,2846584,CC BY-NC-SA,"Rotavirus VP7 is a membrane-associated protein of the endoplasmic reticulum (ER). It is the product of rotavirus gene 9 which potentially encodes a protein of 326 amino acids that contains two amino terminal hydrophobic domains, h1 and h2, each preceded by an initiation codon. Comparison of the size of products derived from altered genes containing coding sequences for both h1 and h2 with those lacking the h1 sequence ('dhl' mutants), indicates that initiation takes place at M30 immediately preceding h2 (residues F32 to L48) and that h2 is cleaved, confirming the studies of others (Stirzaker, S.C., P.L. Whitfeld, D.L. Christie, A.R. Bellamy, and G.W. Both. 1987. J. Cell Biol. 105:2897-2903). Our previous work had shown that deletions in the carboxy end of h2, extending to amino acid 61 in the open reading frame, resulted in secretion of VP7. The region from amino acid number 51-61, present in wild-type VP7 but missing in the secreted mutant delta 47-61, was thus implicated to have a role in ER retention. To test this, a series of chimeric genes were constructed by fusing the first 63 codons of wild-type VP7, delta 1-14 or delta 51-61/dhl, to the mouse salivary alpha-amylase gene, a secretory protein, such that the fusion junction was located at the exact mature terminus of amylase. The chimeric proteins VP7(63)/amylase, delta 1-14(63)/amylase and delta 51-61(63)/dhl/amylase were secreted when expressed in cells and the h2 domain was cleaved when mRNA was translated in vitro. These results imply that the sequence 51-61 is necessary but not sufficient for ER retention. When a second series of VP7/amylase chimera were constructed extending the VP7 contribution to amino acid 111, the product expressed by delta 1-14(111)/amylase was not secreted whereas that of delta 47- 61(111)/amylase was. Significantly, the intracellular delta 1- 14(111)/amylase product exhibited an amylase enzymatic specific activity that was similar to that of the wild-type amylase product. We conclude that two regions of VP7 mediate its retention in the ER, the first lies within the sequence 51-61 and the second within the sequence 62-111, which contains the glycosylation site for VP7. Both regions are necessary for retention, though neither is sufficient alone.",1988 Nov 1,,J Cell Biol,,,True
6485112a971484dfa041b32b35b25707954807db,PMC,The dynamic nature of the Golgi complex,,PMC2115421,2537312,CC BY-NC-SA,"The intracellular transport of newly synthesized G protein of vesicular stomatitis virus is blocked at 20 degrees C and this spanning membrane glycoprotein accumulates in the last Golgi compartment, the trans Golgi- network (TGN). Previous morphological evidence suggested that the TGN enlarged significantly under this condition. In the present study we have used stereological procedures to estimate the volume and surface area of the Golgi stack and the TGN of baby hamster kidney cells under different conditions. The results indicate that the increase in the size of the TGN at 20 degrees C is accompanied by a significant decrease in the surface area and volume of the preceding Golgi compartments. A similar effect is also seen in uninfected cells at 20 degrees C, as well as during normal (37 degrees C) infection with Semliki Forest virus. In the latter case, however, the decrease in the size of the Golgi stack and the increase in that of the TGN is not accompanied by inhibition of transport from the Golgi complex to the cell surface. The results indicate that the Golgi stack and the TGN are dynamic and interrelated structures that are capable of rapid alteration in total surface area in response to changes in the rates of membrane transport.",1989 Feb 1,,J Cell Biol,,,True
a7a5f2d3cff5287f3c65c24cb77de1caf5872687,PMC,"Structure, biosynthesis, and localization of dipeptidyl aminopeptidase B, an integral membrane glycoprotein of the yeast vacuole",,PMC2115513,2647766,CC BY-NC-SA,"We have characterized the structure, biogenesis, and localization of dipeptidyl aminopeptidase B (DPAP B), a membrane protein of the yeast vacuole. An antibody specific for DPAP B recognizes a 120-kD glycoprotein in yeast that behaves like an integral membrane protein in that it is not removed from membranes by high pH Na2CO3 treatment. Inspection of the deduced amino acid sequence of DPAP B reveals a hydrophobic domain near the NH2 terminus that could potentially span a lipid bilayer. The in vitro enzymatic activity and apparent molecular weight of DPAP B are unaffected by the allelic state of PEP4, a gene essential for the proteolytic activation of a number of soluble vacuolar hydrolases. DPAP B is synthesized as a glycosylated precursor that is converted to the mature 120-kD species by carbohydrate addition. The precursor form of DPAP B accumulates in sec mutants (Novick, P., C. Field, and R. Schekman. 1980. Cell. 21:205-215) that are blocked at the ER (sec18) or Golgi apparatus (sec7), but not at secretory vesicles (sec1). Immunolocalization of DPAP B in wild-type or sec1 mutant cells shows that the protein resides in the vacuolar membrane. However, it is present in non-vacuolar compartments in sec18 and sec7 cells, confirming that the delivery of DPAP B is blocked in these mutants. Interestingly, DPAP B appears to stain the nuclear envelope in a sec18 mutant, which is consistent with the accumulation of DPAP B in the ER membrane at the restrictive temperature. These results suggest that soluble and membrane-bound vacuolar proteins use the same stages of the secretory pathway for their transport.",1989 Apr 1,,J Cell Biol,,,True
aeb155140e7a792d4af481ce9d14376046ba856d,PMC,The propeptide of preprosomatostatin mediates intracellular transport and secretion of alpha-globin from mammalian cells,,PMC2115535,2565905,CC BY-NC-SA,"We have investigated the role of the somatostatin propeptide in mediating intracellular transport and sorting to the regulated secretory pathway. Using a retroviral expression vector, two fusion proteins were expressed in rat pituitary (GH3) cells: a control protein consisting of the beta-lactamase signal peptide fused to chimpanzee alpha-globin (142 amino acids); and a chimera of the somatostatin signal peptide and proregion (82 amino acids) fused to alpha-globin. Control globin was translocated into the endoplasmic reticulum as determined by accurate cleavage of its signal peptide; however, alpha- globin was not secreted but was rapidly and quantitatively degraded intracellularly with a t 1/2 of 4-5 min. Globin degradation was insensitive to chloroquine, a drug which inhibits lysosomal proteases, but was inhibited at 16 degrees C suggesting proteolysis occurred during transport to the cis-Golgi apparatus. In contrast to the control globin, approximately 30% of the somatostatin propeptide-globin fusion protein was transported to the distal elements of the Golgi apparatus where it was endoproteolytically processed. Processing of the chimera occurred in an acidic intracellular compartment since cleavage was inhibited by 25 microM chloroquine. 60% of the transported chimera was cleaved at the Arg-Lys processing site in native prosomatostatin yielding ""mature"" alpha-globin. Most significantly, approximately 50% of processed alpha-globin was sorted to the regulated pathway and secreted in response to 8-Br-cAMP. We conclude that the somatostatin propeptide mediated transport of alpha-globin from the endoplasmic reticulum to the trans-Golgi network by protecting molecules from degradation and in addition, facilitated packaging of alpha-globin into vesicles whose secretion was stimulated by cAMP.",1989 May 1,,J Cell Biol,,,True
27c190c3d4fc0884a3b9d79774ee61a0c305c540,PMC,"In vitro membrane assembly of a polytopic, transmembrane protein results in an enzymatically active conformation",,PMC2115569,2654138,CC BY-NC-SA,"In vitro integration of the polytopic, transmembrane lactose permease into membrane vesicles from Escherichia coli is demonstrated. To this end the enzyme was synthesized in a homologous, cell-free transcription- translation system. In this system, synthesis occurred in an essentially membrane-free environment leading to the formation of lactose permease aggregates, which were resistant to protease digestion and detergent solubilization. However, if inverted membrane vesicles from E. coli were included in the synthesis reaction, most de novo- synthesized lactose permease could be recovered from a membrane- containing subfraction (enriched in leader [signal] peptidase activity). This membrane association of lactose permease was Na2CO3 resistant, detergent sensitive, and yielded a distinct pattern of proteolytic cleavage peptides. Moreover, membrane vesicles when present cotranslationally during synthesis of lactose permease, acquired the capability to accumulate lactose, strongly suggesting a correct in vitro assembly of the enzyme. Because of the extensive aggregation of lactose permease synthesized in the absence of membranes, only low amounts originating from the soluble enzyme pool integrated posttranslationally into the membrane vesicles. Unlike the translocation of the outer membrane protein LamB into membrane vesicles, integration of lactose permease was found to be independent of the H+-motive force.",1989 May 1,,J Cell Biol,,,True
13cc84dcf620af030f92f4240637ba43a84004e9,PMC,Selective anchoring in the specific plasma membrane domain: a role in epithelial cell polarity,,PMC2115698,3198691,CC BY-NC-SA,"We have studied the role of restrictions to lateral mobility in the segregation of proteins to apical and basolateral domains of MDCK epithelial cells. Radioimmunoassay and semiquantitative video analysis of immunofluorescence on frozen sections showed that one apical and three basolateral glycoproteins, defined by monoclonal antibodies and binding of beta-2-microglobulin, were incompletely extracted with 0.5% Triton X-100 in a buffer that preserves the cortical cytoskeleton (Fey, E. G., K. M. Wan, and S. Penman. 1984. J. Cell Biol. 98:1973-1984; Nelson, W. T. and P. J. Veshnock. 1986. J. Cell Biol. 103:1751-1766). The marker proteins were preferentially extracted from the ""incorrect"" domain (i.e., the apical domain for a basolateral marker), indicating that the cytoskeletal anchoring was most effective on the ""correct"" domain. The two basolateral markers were unpolarized and almost completely extractable in cells prevented from establishing cell-cell contacts by incubation in low Ca++ medium, while an apical marker was only extracted from the basal surface under the same conditions. Procedures were developed to apply fluorescent probes to either the apical or the basolateral surface of live cells grown on native collagen gels. Fluorescence recovery after photobleaching of predominantly basolateral antigens showed a large percent of cells (28- 52%) with no recoverable fluorescence on the basal domain but normal fluorescence recovery on the apical surface of most cells (92-100%). Diffusion coefficients in cells with normal fluorescence recovery were in the order of 1.1 x 10(-9) cm2/s in the apical domain and 0.6-0.9 x 10(-9) cm2/s in the basal surface, but the difference was not significant. The data from both techniques indicate (a) the existence of mobile and immobile protein fractions in both plasma membrane domains, and (b) that linkage to a domain specific submembrane cytoskeleton plays an important role in the maintenance of epithelial cell surface polarity.",1988 Dec 1,,J Cell Biol,,,True
c4a46bccbf43ff75b7e20f5081f3c5b7a31b7b29,PMC,In vivo analysis of glial cell phenotypes during a viral demyelinating disease in mice,,PMC2115831,2553746,CC BY-NC-SA,"C57 BL/6N mice injected intracranially with the A59 strain of mouse hepatitis virus exhibit extensive viral replication in glial cells of the spinal cord and develop demyelinating lesions followed by virus clearing and remyelination. To study how different glial cell types are affected by the disease process, we combine three-color immunofluorescence labeling with tritiated thymidine autoradiography on 1-micron frozen sections of spinal cord. We use three different glial cell specific antibodies (a) to 2',3' cyclic-nucleotide 3' phosphohydrolase (CNP) expressed by oligodendrocytes, (b) to glial fibrillary acidic protein (GFAP) expressed by astrocytes, and (c) the O4 antibody which binds to O-2A progenitor cells in the rat. These progenitor cells, which give rise to oligodendrocytes and type 2 astrocytes and react with the O4 antibody in the adult central nervous system, were present but rare in the spinal cord of uninfected mice. In contrast, cells with the O-2A progenitor phenotype (O4 + only) were increased in number at one week post viral inoculation (1 WPI) and were the only immunostained cells labeled at that time by a 2-h in vivo pulse of tritiated thymidine. Both GFAP+ only and GFAP+, O4+ astrocytes were also increased in the spinal cord at 1 WPI. Between two and four WPI, the infected spinal cord was characterized by the loss of (CNP+, O4+) oligodendrocytes within demyelinating lesions and the presence of O-2A progenitor cells and O4+, GFAP+ astrocytes, both of which could be labeled with thymidine. As remyelination proceeded, CNP immunostaining returned to near normal and tritiated thymidine injected previously during the demyelinating phase now appeared in CNP+ oligodendrocytes. Thus O4 positive O-2A progenitor cells proliferate early in the course of the demyelinating disease, while CNP positive oligodendrocytes do not. The timing of events suggests that the O-2A progenitors may give rise to new oligodendrocytes and to type 2 astrocytes, both of which are likely to be instrumental in the remyelination process.",1989 Nov 1,,J Cell Biol,,,True
44ca0c52f79a893a551da92dd78e599fbc74b060,PMC,Translational diffusion of class II major histocompatibility complex molecules is constrained by their cytoplasmic domains,,PMC2115898,2557353,CC BY-NC-SA,"Site-directed mutagenesis in vitro was used to introduce stop codons in the genomic DNA of the alpha and beta chains of the murine class II major histocompatibility complex antigen, I-Ak. Mutated DNA was transfected into B lymphoma cells that were then selected by neomycin resistance and for their ability to express I-Ak molecules on their plasma membrane. The translational diffusion coefficient (Dlat) of I-Ak molecules composed of a wild-type beta chain paired with an alpha chain missing either 6 or 12 amino acids from the cytoplasmic domain is on the average threefold higher than the Dlat of wild-type I-Ak molecules as measured by fluorescence photobleaching and recovery. The removal of 12 amino acids from the cytoplasmic domain of the beta chain did not change the Dlat value from that of wild-type I-Ak if the truncated beta chain was paired with a wild-type alpha chain. Removing all amino acids of the cytoplasmic domains of both the alpha and beta chains resulted in a 10-fold increase in the Dlat, the highest value for any of the truncated I-Ak molecules tested. These data indicate that the carboxy- terminal six amino acids of the cytoplasmic domain of the alpha chain and the six plasma membrane-proximal amino acids of the beta chain are important in constraining the translational diffusion of I-Ak molecules in the plasma membrane.",1989 Dec 1,,J Cell Biol,,,True
26b944ce8d2f033704c7aeef38b0c128c0dd18be,PMC,Sorting within the regulated secretory pathway occurs in the trans- Golgi network,,PMC2115992,2295680,CC BY-NC-SA,"Bioactive peptides cleaved from the egg-laying hormone precursor in the bag cell neurons of Aplysia are sorted into distinct dense core vesicle classes (DCVs). Bag cell prohormone processing can be divided into two stages, an initial cleavage occurring in a late Golgi compartment, which is not blocked by monensin, and later cleavages that occur within DCVs and are blocked by monensin. Prohormone intermediates are sorted in the trans-Golgi network. The large soma-specific DCVs turn over, while the small DCVs are transported to processes for regulated release. Thus, protein trafficking differentially regulates the levels and localization of multiple biologically active peptides derived from a common prohormone.",1990 Jan 1,,J Cell Biol,,,True
63aed9fa99e7df7846c24993fbf4d7aebb4d957a,PMC,In vitro analysis of the oligodendrocyte lineage in mice during demyelination and remyelination,,PMC2116277,2167897,CC BY-NC-SA,"A demyelinating disease induced in C57B1/6N mice by intracranial injection of a coronavirus (murine hepatitis virus strain A59) is followed by functional recovery and efficient CNS myelin repair. To study the biological properties of the cells involved in this repair process, glial cells were isolated and cultured from spinal cords of these young adult mice during demyelination and remyelination. Using three-color immunofluorescence combined with [3H]thymidine autoradiography, we have analyzed the antigenic phenotype and mitotic potential of individual glial cells. We identified oligodendrocytes with an antibody to galactocerebroside, astrocytes with an antibody to glial fibrillary acidic protein, and oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells with the O4 antibody. Cultures from demyelinated tissue differed in several ways from those of age-matched controls: first, the total number of O-2A lineage cells was strikingly increased; second, the O-2A population consisted of a higher proportion of O4-positive astrocytes and cells of mixed oligodendrocyte-astrocyte phenotype; and third, all the cell types within the O-2A lineage showed enhanced proliferation. This proliferation was not further enhanced by adding PDGF, basic fibroblast growth factor (bFGF), or insulin-like growth factor I (IGF-I) to the defined medium. However, bFGF and IGF-I seemed to influence the fate of O-2A lineage cells in cultures of demyelinated tissue. Basic FGF decreased the percentage of cells expressing galactocerebroside. In contrast, IGF-I increased the relative proportion of oligodendrocytes. Thus, O-2A lineage cells from adult mice display greater phenotypic plasticity and enhanced mitotic potential in response to an episode of demyelination. These properties may be linked to the efficient remyelination achieved in this demyelinating disease.",1990 Sep 1,,J Cell Biol,,,True
4b1b2e95b29b2fb4926c6c0191689f86537985bb,PMC,The signal sequence of the p62 protein of Semliki Forest virus is involved in initiation but not in completing chain translocation,,PMC2116283,2391367,CC BY-NC-SA,"So far it has been demonstrated that the signal sequence of proteins which are made at the ER functions both at the level of protein targeting to the ER and in initiation of chain translocation across the ER membrane. However, its possible role in completing the process of chain transfer (see Singer, S. J., P. A. Maher, and M. P. Yaffe. Proc. Natl. Acad. Sci. USA. 1987. 84:1015-1019) has remained elusive. In this work we show that the p62 protein of Semliki Forest virus contains an uncleaved signal sequence at its NH2-terminus and that this becomes glycosylated early during synthesis and translocation of the p62 polypeptide. As the glycosylation of the signal sequence most likely occurs after its release from the ER membrane our results suggest that this region has no role in completing the transfer process.",1990 Sep 1,,J Cell Biol,,,True
6755e8b9e6792097d1be5bdf0041c3df1980ec60,PMC,Compartmentation of the Golgi complex: brefeldin-A distinguishes trans- Golgi cisternae from the trans-Golgi network,,PMC2116293,2167898,CC BY-NC-SA,"The Golgi complex is composed of at least four distinct compartments, termed the cis-, medial, and trans-Golgi cisternae and the trans-Golgi network (TGN). It has recently been reported that the organization of the Golgi complex is disrupted in cells treated with the fungal metabolite, brefeldin-A. Under these conditions, it was shown that resident enzymes of the cis-, medial, and trans-Golgi return to the ER. We report here that 300-kD mannose 6-phosphate receptors, when pulse- labeled within the ER of brefeldin-A-treated cells, acquired numerous N- linked galactose residues with a half time of approximately 2 h, as measured by their ability to bind to RCA-I lectin affinity columns. In contrast, Limax flavus lectin chromatography revealed that less than 10% of these receptors acquired sialic acid after 8 h in brefeldin-A. Two lines of evidence suggested that proteins within and beyond the TGN did not return to the ER in the presence of brefeldin-A. First, the majority of 300-kD mannose 6-phosphate receptors present in the TGN and endosomes did not return to the ER after up to 6 h in brefeldin-A, as determined by their failure to contact galactosyltransferase that had relocated there. Moreover, although mannose 6-phosphate receptors did not acquire sialic acid when present in the ER of brefeldin-A-treated cells, they were readily sialylated when labeled at the cell surface and transported to the TGN. These experiments indicate that galactosyltransferase, a trans-Golgi enzyme, returns to the endoplasmic reticulum in the presence of brefeldin-A, while the bulk of sialyltransferase, a resident of the TGN, does not. Our findings support the proposal that the TGN is a distinct, fourth compartment of the Golgi apparatus that is insensitive to brefeldin-A.",1990 Sep 1,,J Cell Biol,,,True
a2986c7d52f824dd89fc02e5c1fcab46b3f37524,PMC,A novel subset of putative stem/progenitor CD34(+)Oct-4(+) cells is the major target for SARS coronavirus in human lung,http://dx.doi.org/10.1084/jem.20070462,PMC2118498,17923501,CC BY-NC-SA,"Identification of the nature of severe acute respiratory syndrome (SARS)-infected cells is crucial toward understanding the pathogenesis. Using multicolor colocalization techniques, we previously reported that SARS(+) cells in the lung of fatally infected patients expressed the only known functional receptor, angiotensin-converting enzyme 2, and also a binding receptor, liver/lymph node–specific ICAM-3–grabbing non-integrin (CD209L). In this study, we show that SARS-infected cells also express the stem/progenitor cell markers CD34 and Oct-4, and do not express cytokeratin or surfactant. These putative lung stem/progenitor cells can also be identified in some non-SARS individuals and can be infected by SARS-coronavirus ex vivo. Infection of these cells may contribute to the loss of lung repair capacity that leads to respiratory failure as clinically observed.",2007 Oct 29,"['Chen, Yongxiong', 'Chan, Vera Sau-Fong', 'Zheng, Bojian', 'Chan, Kelvin Yuen-Kwong', 'Xu, Xiaoning', 'To, Leo Yuk-Fai', 'Huang, Fang-Ping', 'Khoo, Ui-Soon', 'Lin, Chen-Lung Steve']",J Exp Med,,,True
c055818c61327ee072c403cb911793c9c49ca7bf,PMC,"Effect of antigen/antibody ratio on macrophage uptake, processing, and presentation to T cells of antigen complexed with polyclonal antibodies",,PMC2118742,1985125,CC BY-NC-SA,"Activation of a galactosidase-specific murine T hybridoma clone and of a human tetanus toxoid-specific T clone by antigen-presenting cells (APC) was used to evaluate the regulatory function of antibodies complexed with the relevant antigen. Complexed antigen, in fact, is taken up with high efficiency thanks to Fc receptors borne by APC. Antibody/antigen ratio in the complexes proved to be a critical parameter in enhancing antigen presentation. Complexes in moderate antibody excess provided optimal T cell activation independently of the physical state of the complexes (precipitated by a second antibody or solubilized by complement). Complexes in extreme antibody excess, on the contrary, did not yield T cell activation although taken up by APC efficiently. The effect of antibodies at extreme excess was observed with substimulatory dose of antigen (loss of potentiation) and with optimal dose of antigen (loss of stimulation). An excess of specific polyclonal antibodies hampers proteolytic degradation of antigen in vitro, supporting the view that a similar mechanism may operate within the APC that have internalized immune complexes in extreme antibody excess. The possibility that immune complex forming in extreme antibody excess may turn off the T cell response is proposed as a regulatory mechanism.",1991 Jan 1,,J Exp Med,,,True
cf6a16717c4b118d2e8bca72fe7dd28c2f2c2cdb,PMC,Transferrin receptor mediates uptake and presentation of hepatitis B envelope antigen by T lymphocytes,,PMC2119224,1569393,CC BY-NC-SA,"Human activated T lymphocytes expressing class II molecules are able to present only complex antigens that bind to their own surface receptors, and thus can be captured, internalized, and processed through the class II major histocompatibility complex processing pathway. We have used the antigen-presenting T cell system to identify the viral receptor used by hepatitis B virus (HBV) to enter cells, as well as the sequence of HB envelope antigen (HBenvAg) involved in this interaction. Results show that both CD4+ and CD8+ T clones can process and present HBenvAg to class II-restricted cytotoxic T lymphocytes and that the CD71 transferrin receptor (TfR) is involved in efficient HBenvAg uptake by T cells. Moreover, we provide evidence that the HBenvAg sequence interacting with the T cell surface is contained within the pre-S2 region. Since TfR is also expressed on hepatocytes, it might represent a portal of cellular entry for HBV infection. This system of antigen presentation by T cells may serve as a model to study both lymphocyte receptors used by lymphocytotropic viruses and viral proteins critical to bind them.",1992 May 1,,J Exp Med,,,True
9363422a0f9b40cd6bb8f6c7fbbcaadf146f20a6,PMC,Monoclonal antiprothrombinase (3D4.3) prevents mortality from murine hepatitis virus (MHV-3) infection,,PMC2119354,1324969,CC BY-NC-SA,"The induction of monocyte/macrophage procoagulant activity (PCA) has been implicated in the pathogenesis of murine hepatitis virus strain 3 (MHV-3) infection and disease. Previously, we have shown that induction of PCA by MHV-3 correlated with resistance/susceptibility to infection in different mouse strains. In this study, all BALB/cJ mice that were infected with 10(3) plaque-forming units of MHV-3 developed severe liver disease and died within 96-120 h. Examination of the livers of these animals showed marked hepatic necrosis, deposition of fibrin, and cellular expression of PCA by direct immunofluorescence staining in areas of necrosis as well as in hepatic sinusoids. Splenic mononuclear cells recovered from these mice expressed high concentrations of PCA with time after infection. Infusion into mice of a high-titered monoclonal antibody that neutralized PCA (3D4.3) attenuated the development of hepatic necrosis and enhanced survival in a dose- dependent manner. All of the animals receiving 100 micrograms, and 44% and 22% of the animals that received 50 and 25 micrograms per day, respectively, survived for 10 d and made a full recovery. Administration of the antibody resulted in a dose-dependent reduction in fibrin deposition, PCA expression as detected by direct immunofluorescence staining and by a functional assay. In animals treated with high concentrations of antibody, titers of antibody to PCA fell from 87 +/- 15 micrograms/ml to 100 +/- 7 ng/ml during the active phase of the disease, consistent with sequestration due to binding of the immunoglobulin to cells expressing PCA. Surviving animals, when rechallenged with MHV-3, had a 40% mortality, consistent with the known rates of metabolism of immunoglobulin. This further suggested that protection was by a passive mechanism. The results reported here demonstrate that a neutralizing antibody to PCA protects animals from fulminant hepatitis and death associated with MHV-3 infection, and supports the notion that PCA is a potent inflammatory mediator that plays a pivotal role in the pathogenesis of liver injury resulting from MHV-3 infection.",1992 Sep 1,,J Exp Med,,,True
e0d4c25b7e80c41abb0a816770a803b29746b2ee,PMC,Triggering through CD16 or phorbol esters enhances adhesion of NK cells to laminin via very late antigen 6,,PMC2119439,1402670,CC BY-NC-SA,"Very late antigens VLA-1, VLA-2, VLA-3, and VLA-6, belonging to the beta 1 subfamily of integrins, have been identified as receptors for different binding domains of laminin (LM). We have detected VLA-6, but not VLA-1 and VLA-2 on a subset (50-70%) of fresh peripheral blood CD3- , CD16+, CD56+ human natural killer (NK) cells by immunofluorimetric and biochemical analysis. Binding assays performed on LM-coated plates showed that 10-15% of NK cells spontaneously adhere to LM, and this adhesion is mediated by VLA-6. Activation of NK cells through CD16 triggering or by phorbol ester results in a rapid increase of adhesion to LM, which is still mediated by VLA-6. The enhanced adhesiveness is not associated with changes in beta 1 LM receptor expression, while it correlates with changes in the phosphorylation status of alpha 6 subunit. The expression of VLA-6 on NK cells and the modulation of its avidity by activating stimuli may be relevant for NK cell migration and tissue location during inflammation or immune response.",1992 Nov 1,,J Exp Med,,,True
5dd80841cfa8fbf952df8516dd9ff3e4233b977f,PMC,The first membrane spanning region of the lamin B receptor is sufficient for sorting to the inner nuclear membrane,,PMC2119546,8381121,CC BY-NC-SA,"The lamin B receptor (LBR) is a polytopic integral membrane protein localized exclusively in the inner nuclear membrane domain of the nuclear envelope. Its cDNA deduced primary structure consists of a highly charged amino-terminal domain of 205 residues that faces the nucleoplasm followed by a hydrophobic domain with eight potential transmembrane segments. To identify determinants that sort LBR from its site of integration (RER and outer nuclear membrane) to the inner nuclear membrane, we prepared full-length, truncated, and chimeric cDNA constructs of chick LBR, transfected these into mammalian cells and detected the expressed protein by immunofluorescence microscopy using appropriate antibodies. Surprisingly, we found that the determinants for sorting of LBR to the inner nuclear membrane reside in a region comprising its first transmembrane sequence plus flanking residues on either side. The other transmembrane regions as well as the nucleoplasmic domain are not required for sorting. We propose that the first transmembrane segment of LBR interacts specifically with another transmembrane segment and consider several mechanisms by which such specific interaction could result in sorting to the inner nuclear membrane.",1993 Feb 1,,J Cell Biol,,,True
377e2c575da8f034d4f9f34d7ad6c4395487f348,PMC,Assembly of vaccinia virus: role of the intermediate compartment between the endoplasmic reticulum and the Golgi stacks,,PMC2119557,8486734,CC BY-NC-SA,"Vaccinia virus, the prototype of the Poxviridae, is a large DNA virus which replicates in the cytoplasm of the host cell. The assembly pathway of vaccinia virus displays several unique features, such as the production of two structurally distinct, infectious forms. One of these, termed intracellular naked virus (INV), remains cells associated while the other, termed extracellular enveloped virus (EEV), is released from the cell. In addition, it has long been believed that INVs acquire their lipid envelopes by a unique example of de novo membrane biogenesis. To examine the structure and assembly of vaccinia virus we have used immunoelectron microscopy using antibodies to proteins of different subcellular compartments as well as a phospholipid analysis of purified INV and EEV. Our data are not consistent with the de novo model of viral membrane synthesis but rather argue that the vaccinia virus DNA becomes enwrapped by a membrane cisterna derived from the intermediate compartment between the ER and the Golgi stacks, thus acquiring two membranes in one step. Phospholipid analysis of purified INV supports its derivation from an early biosynthetic compartment. This unique assembly process is repeated once more when the INV becomes enwrapped by an additional membrane cisterna, in agreement with earlier reports. The available data suggest that after fusion between the outer envelope and the plasma membrane, mature EEV is released from the cell.",1993 May 1,,J Cell Biol,,,True
05b5ca303bd262f2a8e7d9d05d203f023867d0ed,PMC,Membrane protein retention in the yeast Golgi apparatus: dipeptidyl aminopeptidase A is retained by a cytoplasmic signal containing aromatic residues,,PMC2119699,8509444,CC BY-NC-SA,"The mechanism by which yeast dipeptidyl aminopeptidase (DPAP) A, type II integral membrane protein, is retained in the late Golgi apparatus has been investigated. Prior work demonstrated that the 118-amino acid cytoplasmic domain is both necessary and sufficient for Golgi retention and that mutant or overexpressed DPAP A no longer retained in the Golgi was delivered directly to the vacuolar membrane (Roberts, C. J., S. F. Nothwehr, and T. H. Stevens. 1992. J. Cell Biol. 119:69-83). Replacement of the DPAP A transmembrane domain with a synthetic hydrophobic sequence did not affect either Golgi retention of DPAP A or vacuolar delivery of the retention-defective form of DPAP A. These results indicate that the DPAP A transmembrane domain is not involved in either Golgi retention or targeting of this membrane protein. A detailed mutational analysis of the cytoplasmic domain of DPAP A indicated that the most important elements for retention were within the eight residue stretch 85-92. A 10-amino acid region from DPAP A (81- 90) was sufficient for Golgi retention of alkaline phosphatase, a type II vacuolar membrane protein. Detailed mutational analysis within this 10-amino acid sufficient region demonstrated that a Phe-X-Phe-X-Asp motif was absolutely required for efficient retention. The efficiency of Golgi retention via the DPAP A signal could be diminished by overexpression of wild type but not retention-defective versions of Kex2p, another late Golgi membrane protein, suggesting that multiple Golgi membrane proteins may be retained by a common machinery. These results imply a role for a cytoplasmic signal involving aromatic residues in retention of late Golgi membrane proteins in the yeast Saccharomyces cerevisiae.",1993 Jun 2,,J Cell Biol,,,True
e984059fedde6d22ac47555e59c76449a5d8a589,PMC,The amino-terminal domain of the lamin B receptor is a nuclear envelope targeting signal,,PMC2119726,7679672,CC BY-NC-SA,"The lamin B receptor (LBR) is a polytopic protein of the inner nuclear membrane. It is synthesized without a cleavable amino-terminal signal sequence and composed of a nucleoplasmic amino-terminal domain of 204 amino acids followed by a hydrophobic domain with eight putative transmembrane segments. To identify a nuclear envelope targeting signal, we have examined the cellular localization by immunofluorescence microscopy of chicken LBR, its amino-terminal domain and chimeric proteins transiently expressed in transfected COS-7. Full- length LBR was targeted to the nuclear envelope. The amino-terminal domain, without any transmembrane segments, was transported to the nucleus but excluded from the nucleolus. When the amino-terminal domain of LBR was fused to the amino-terminal side of a transmembrane segment of a type II integral membrane protein of the ER/plasma membrane, the chimeric protein was targeted to the nuclear envelope, likely the inner nuclear membrane. When the amino-terminal domain was deleted from LBR and replaced by alpha-globin, the chimeric protein was retained in the ER. These findings demonstrate that the amino-terminal domain of LBR is targeted to the nucleus after synthesis in the cytoplasm and that this polypeptide can function as a nuclear envelope targeting signal when located at the amino terminus of a type II integral membrane protein synthesized on the ER.",1993 Mar 1,,J Cell Biol,,,True
9c0ebc47e2a6b0592a18266c968e2aa28da9575e,PMC,Localization of TGN38 to the trans-Golgi network: involvement of a cytoplasmic tyrosine-containing sequence,,PMC2119736,8436587,CC BY-NC-SA,"Protein localization to the TGN was investigated by examining the subcellular distribution of chimeric proteins in which the cytoplasmic and/or transmembrane domains of the TGN protein, TGN38, were substituted for the analogous domains of the plasma membrane protein, Tac. Using immunofluorescence and immunoelectron microscopy, the COOH- terminal cytoplasmic domain of TGN38 was found to be sufficient for localization of the chimeric proteins to the TGN. Deletion analysis identified an 11-amino acid segment containing the critical sequence, YQRL, as being sufficient for TGN localization. TGN localization was abrogated by mutation of the tyrosine or leucine residues in this sequence to alanine, or of the arginine residue to aspartate. In addition to specifying TGN localization, the 11-amino acid segment was active as an internalization signal, although the property of internalization alone was insufficient to confer TGN localization. Overexpression of chimeric proteins containing TGN localization determinants resulted in their detection at the plasma membrane and in intracellular vesicles, and abolished detection of endogenous TGN38. These results suggest that discrete cytoplasmic determinants can mediate protein localization to the TGN, and reveal a novel role for tyrosine-based motifs in this process.",1993 Mar 1,,J Cell Biol,,,True
a621b8667d221681dda8e3291d8b2c99a3636868,PMC,Effect of caffeine and reduced temperature (20 degrees C) on the organization of the pre-Golgi and the Golgi stack membranes,,PMC2119759,8449979,CC BY-NC-SA,"In the present study we have dissected the transport pathways between the ER and the Golgi complex using a recently introduced (Kuismanen, E., J. Jantti, V. Makiranta, and M. Sariola. 1992. J. Cell Sci. 102:505- 513) inhibition of transport by caffeine at 20 degrees C. Recovery of the Golgi complex from brefeldin A (BFA) treatment was inhibited by caffeine at reduced temperature (20 degrees C) suggesting that caffeine inhibits the membrane traffic between the ER and the Golgi complex. Caffeine at 20 degrees C did not inhibit the BFA-induced retrograde movement of the Golgi membranes. Further, incubation of the cells in 10 mM caffeine at 20 degrees C had profound effects on the distribution and the organization of the pre-Golgi and the Golgi stack membranes. Caffeine treatment at 20 degrees C resulted in a selective and reversible translocation of the pre- and cis-Golgi marker protein (p58) to the periphery of the cell. This caffeine-induced effect on the Golgi complex was different from that induced by BFA, since mannosidase II, a Golgi stack marker, remained perinuclearly located and the Golgi stack coat protein, beta-COP, was not detached from Golgi membranes in the presence of 10 mM caffeine at 20 degrees C. Electron microscopic analysis showed that, in the presence of caffeine at 20 degrees C, the morphology of the Golgi stack was altered and accumulation of numerous small vesicles in the Golgi region was observed. The results in the present study suggest that caffeine at reduced temperature (20 degrees C) reveals a functional interface between the pre-Golgi and the Golgi stack.",1993 Mar 2,,J Cell Biol,,,True
1bfeba839c9c98eb6e49ceb13cfcdba28620a61d,PMC,Oligomerization of a membrane protein correlates with its retention in the Golgi complex,,PMC2119850,8397214,CC BY-NC-SA,"The first membrane-spanning domain (m1) of the M glycoprotein of avian coronavirus (formerly called E1) is sufficient to retain this protein in the cis-Golgi. When the membrane-spanning domain of a protein which is efficiently delivered to the plasma membrane (VSV G protein) is replaced with m1, the resulting chimera (Gm1) is retained in the Golgi (Swift, A. M., and C. E. Machamer. 1991. J. Cell Biol. 115:19-30). When assayed in sucrose gradients, we observed that Gm1 formed a large oligomer, and that much of this oligomer was SDS resistant and stayed near the top of the stacking gel of an SDS-polyacrylamide gel. The unusual stability of the oligomer allowed it to be detected easily. Gm1 mutants with single amino acid substitutions in the m1 domain that were retained in the Golgi complex formed SDS-resistant oligomers, whereas mutants that were rapidly released to the plasma membrane did not. Oligomerization was not detected immediately after synthesis of Gm1, but occurred gradually with a lag of approximately 10 min, suggesting that it is not merely aggregation of misfolded proteins. Furthermore, oligomerization did not occur under several conditions that block ER to Golgi transport. The lumenal domain was not required for oligomerization since another chimera (alpha m1G), where the lumenal domain of Gm1 was replaced by the alpha subunit of human chorionic gonadotropin, also formed an SDS-resistant oligomer, and was able to form hetero-oligomers with Gm1 as revealed by coprecipitation experiments. SDS resistance was conferred by the cytoplasmic tail of VSV G, because proteolytic digestion of the tail in microsomes containing Gm1 oligomers resulted in loss of SDS resistance, although the protease-treated material continued to migrate as a large oligomer on sucrose gradients. Interestingly, treatment of cells with cytochalasin D blocked formation of SDS-resistant (but not SDS- sensitive) oligomers. Our data suggest that SDS-resistant oligomers form as newly synthesized molecules of Gm1 arrive at the Golgi complex and may interact (directly or indirectly) with an actin-based cytoskeletal matrix. The oligomerization of Gm1 and other resident proteins could serve as a mechanism for their retention in the Golgi complex.",1993 Sep 2,,J Cell Biol,,,True
1fe6e8c22714c1484434a2b5b334bedf7f216739,PMC,Characterization of the budding compartment of mouse hepatitis virus: evidence that transport from the RER to the Golgi complex requires only one vesicular transport step,,PMC2119890,8294506,CC BY-NC-SA,"Mouse hepatitis coronavirus (MHV) buds into pleomorphic membrane structures with features expected of the intermediate compartment between the ER and the Golgi complex. Here, we characterize the MHV budding compartment in more detail in mouse L cells using streptolysin O (SLO) permeabilization which allowed us to better visualize the membrane structures at the ER-Golgi boundary. The MHV budding compartment shares membrane continuities with the rough ER as well as with cisternal elements on one side of the Golgi stack. It also labeled with p58 and rab2, two markers of the intermediate compartment, and with PDI, usually considered to be a marker of the rough ER. The membranes of the budding compartment, as well as the budding virions themselves, but not the rough ER, labeled with the N-acetyl- galactosamine (GalNAc)-specific lectin Helix pomatia. When the SLO- permeabilized cells were treated with guanosine 5'-(3-O- thio)triphosphate (GTP gamma S), the budding compartment accumulated a large number of beta-cop-containing buds and vesicular profiles. Complementary biochemical experiments were carried out to determine whether vesicular transport was required for the newly synthesized M protein, that contains only O-linked oligosaccharides, to acquire first, GalNAc and second, the Golgi modifications galactose and sialic acid. The results from both in vivo studies and from the use of SLO- permeabilized cells showed that, while GalNAc addition occurred under conditions which block vesicular transport, both cytosol and ATP were prerequisites for the M protein oligosaccharides to acquire Golgi modifications. Collectively, our data argue that transport from the rough ER to the Golgi complex requires only one vesicular transport step and that the intermediate compartment is a specialized domain of the endoplasmatic reticulum that extends to the first cisterna on the cis side of the Golgi stack.",1994 Jan 1,,J Cell Biol,,,True
c40185936592afcdc0681000e25585dd58f5ef41,PMC,The TGN38 glycoprotein contains two non-overlapping signals that mediate localization to the trans-Golgi network,,PMC2120028,8163544,CC BY-NC-SA,"The membrane-spanning and cytoplasmic domains of CD4 and CD8 were replaced by those of TGN38. After transient expression in HeLa cells, the location of the hybrid proteins was determined using immunofluorescence and quantitative immuno-electron microscopy, FACS analysis and metabolic labeling. The membrane-spanning domain was found to contain a signal that localized hybrid proteins to the TGN. This was in addition to the signal previously identified in the cytoplasmic domain (Bos, K., C. Wraight, and K. Stanley. 1993. EMBO (Eur. Mol. Biol. Organ) J. 12:2219-2228. Humphrey, J. S., P. J. Peters, L. C. Yuan, and J. S. Bonifacino. 1993. J. Cell Biol. 120:1123-1135. Wong, S. H., and W. Hong. 1993. J. Biol. Chem. 268:22853-22862). The different properties of these two signals suggest that each operates by a different mechanism.",1994 Apr 2,,J Cell Biol,,,True
153c3a86e8939de3ca0331ea95b68f8bb4a3e395,PMC,Rab1 and Ca2+ are required for the fusion of carrier vesicles mediating endoplasmic reticulum to Golgi transport,,PMC2120032,8163543,CC BY-NC-SA,"Members of the rab/YPT1/SEC4 gene family of small molecular weight GTPases play key roles in the regulation of vesicular traffic between compartments of the exocytic pathway. Using immunoelectron microscopy, we demonstrate that a dominant negative rab1a mutant, rab1a(N124I), defective for guanine nucleotide binding in vitro, leads to the accumulation of vesicular stomatitis virus glycoprotein (VSV-G) in numerous pre-cis-Golgi vesicles and vesicular-tubular clusters containing rab1 and beta-COP, a subunit of the coatomer complex. Similar to previous observations (Balch et al. 1994. Cell. 76:841-852), VSV-G was concentrated nearly 5-10-fold in vesicular carriers that accumulate in the presence of the rab1a(N124I) mutant. VSV-G containing vesicles and vesicular-tubular clusters were also found to accumulate in the presence of a rab1a effector domain peptide mimetic that inhibits endoplasmic reticulum to Golgi transport, as well as in the absence of Ca2+. These results suggest that the combined action of a Ca(2+)-dependent protein and conformational changes associated with the GTPase cycle of rab1 are essential for a late targeting/fusion step controlling the delivery of vesicles to Golgi compartments.",1994 Apr 2,,J Cell Biol,,,True
17c30925f6e62319c5049126e8fddbc1410e9983,PMC,Distinct molecular mechanisms for protein sorting within immature secretory granules of pancreatic beta-cells,,PMC2120086,8027188,CC BY-NC-SA,"In the beta-cells of pancreatic islets, insulin is stored as the predominant protein within storage granules that undergo regulated exocytosis in response to glucose. By pulse-chase analysis of radiolabeled protein condensation in beta-cells, the formation of insoluble aggregates of regulated secretory protein lags behind the conversion of proinsulin to insulin. Condensation occurs within immature granules (IGs), accounting for passive protein sorting as demonstrated by constitutive-like secretion of newly synthesized C- peptide in stoichiometric excess of insulin (Kuliawat, R., and P. Arvan. J. Cell Biol. 1992. 118:521-529). Experimental manipulation of condensation conditions in vivo reveals a direct relationship between sorting of regulated secretory protein and polymer assembly within IGs. By contrast, entry from the trans-Golgi network into IGs does not appear especially selective for regulated secretory proteins. Specifically, in normal islets, lysosomal enzyme precursors enter the stimulus-dependent secretory pathway with comparable efficiency to that of proinsulin. However, within 2 h after synthesis (the same period during which proinsulin processing occurs), newly synthesized hydrolases are fairly efficiently relocated out of the stimulus- dependent pathway. In tunicamycin-treated islets, while entry of new lysosomal enzymes into the regulated secretory pathway continues unperturbed, exit of nonglycosylated hydrolases from this pathway does not occur. Consequently, the ultimate targeting of nonglycosylated hydrolases in beta-cells is to storage granules rather than lysosomes. These results implicate a post-Golgi mechanism for the active removal of lysosomal hydrolases away from condensed granule contents during the storage process for regulated secretory proteins.",1994 Jul 1,,J Cell Biol,,,True
d657cc5e24009f5081425da4d8c3b6467b85df1d,PMC,Retention of p63 in an ER-Golgi intermediate compartment depends on the presence of all three of its domains and on its ability to form oligomers,,PMC2120087,8027183,CC BY-NC-SA,"The type II membrane protein p63 is a resident protein of a membrane network interposed between rough ER and Golgi apparatus. To study the retention of p63, mutant forms were expressed in COS cells and the intracellular distribution determined by immunofluorescence microscopy. Investigation of chimeric constructs between p63 and the plasma membrane protein dipeptidylpeptidase IV showed that protein sequences from all three domains of the p63 protein are required to achieve complete intracellular retention. Mutational analysis of the 106-amino acid cytoplasmic tail of p63 revealed that the NH2-terminal 23 amino acids are necessary for retention. When p63 was solubilized with Triton X-100 and subjected to centrifugation at 100,000 g, it formed large, insoluble oligomers, particularly at neutral pH and below. A comparison of the behavior of wildtype and mutant p63 proteins in this assay revealed a perfect correlation between the formation of large oligomers and correct intracellular retention. These results suggest that self- association may be a major mechanism by which p63 is retained between the rough ER and the Golgi apparatus.",1994 Jul 1,,J Cell Biol,,,True
8acd6f32fca98b572ad9c5cce743dd21d26b115e,PMC,Membrane insertion of gap junction connexins: polytopic channel forming membrane proteins,,PMC2120216,7929580,CC BY-NC-SA,"Connexins, the proteins that form gap junction channels, are polytopic plasma membrane (PM) proteins that traverse the plasma membrane bilayer four times. The insertion of five different connexins into the membrane of the ER was studied by synthesizing connexins in translation- competent cell lysates supplemented with pancreatic ER-derived microsomes, and by expressing connexins in vivo in several eucaryotic cell types. In addition, the subcellular distribution of the connexins was determined. In vitro-synthesis in the presence of microsomes resulted in the signal recognition particle-dependent membrane insertion of the connexins. The membrane insertion of all connexins was accompanied by an efficient proteolytic processing that was dependent on the microsome concentration. Endogenous unprocessed connexins were detectable in the microsomes used, indicating that the pancreatic microsomes serve as a competent recipient in vivo for unprocessed full length connexins. Although oriented with their amino terminus in the cytoplasm, the analysis of the cleavage reaction indicated that an unprecedented processing by signal peptidase resulted in the removal of an amino-terminal portion of the connexins. Variable amounts of similar connexin cleavage products were also identified in the ER membranes of connexin overexpressing cells. The amount generated correlated with the level of protein expression. These results demonstrate that the connexins contain a cryptic signal peptidase cleavage site that can be processed by this enzyme in vitro and in vivo in association with their membrane insertion. Consequently, a specific factor or condition must be required to prevent this aberrant processing of connexins under normal conditions in the cell.",1994 Oct 2,,J Cell Biol,,,True
aa09cbc24e8aa582a402d4542656f0a5b49963bb,PMC,"Clathrin-dependent localization of alpha 1,3 mannosyltransferase to the Golgi complex of Saccharomyces cerevisiae",,PMC2120240,7962051,CC BY-NC-SA,"Posttranslational modification of yeast glycoproteins with alpha 1,3- linked mannose is initiated within a Golgi compartment analogous to the medial Golgi cisternae of higher eukaryotes. We have characterized the synthesis, posttranslational modification, and localization of the yeast alpha 1,3 mannosyltransferase (Mnn1p) using antibodies prepared against a segment of this protein expressed in bacteria. Mnn1p is initially synthesized as a 98.5-kD, type II integral membrane glycoprotein that is modified with both N- and O-linked oligosaccharides. It is subject to a slow, incremental increase in molecular mass that is dependent upon protein transport to the Golgi complex. Self-modification of Mnn1p with alpha 1,3 mannose epitopes, primarily on O-linked oligosaccharides, is at least partly responsible for the incremental increase in molecular mass. Mnn1p is a resident protein of the Golgi complex and colocalizes with guanosine diphosphatase to at least two physically distinct Golgi compartments by sucrose gradient fractionation, one of which may be a late Golgi compartment that also contains the Kex2 endopeptidase. Surprisingly, we found that a significant fraction of Mnn1p is mislocalized to the plasma membrane in a clathrin heavy chain temperature sensitive mutant while guanosine diphosphatase remains intracellular. A mutant Mnn1p that lacks the NH2-terminal cytoplasmic tail is properly localized to the Golgi complex, indicating that clathrin does not mediate Mnnlp Golgi retention by a direct interaction with the Mnn1p cytoplasmic tail. These results indicate that clathrin plays a broader role in the localization of Golgi proteins than anticipated.",1994 Nov 1,,J Cell Biol,,,True
f0813fe3f70fb9a52ec5944b43bdd953a08cc49a,PMC,The v-sis oncoprotein loses transforming activity when targeted to the early Golgi complex,,PMC2120273,7806564,CC BY-NC-SA,"The location of autocrine interactions between the v-sis protein and PDGF receptors remains uncertain and controversial. To examine whether receptor-ligand interactions can occur intracellularly, we have constructed fusion proteins that anchor v-sis to specific intracellular membranes. Fusion of a cis-Golgi retention signal from a coronavirus E1 glycoprotein to v-sis protein completely abolished its transforming ability when transfected into NIH3T3 cells. Fusion proteins incorporating mutations in this retention signal were not retained within the Golgi complex but instead were transported to the cell surface, resulting in efficient transformation. All chimeric proteins were shown to dimerize properly. Derivatives of some of these constructs were also constructed bearing the cytoplasmic tail from the glycoprotein of vesicular stomatitis virus (VSV-G). These constructs allowed examination of subcellular localization by double-label immunofluorescence, using antibodies that distinguish between the extracellular PDGF-related domain and the VSV-G cytoplasmic tail. Colocalization of sis-E1-G with Golgi markers confirmed its targeting to the early Golgi complex. The sis-E1 constructs, targeted to the early Golgi complex, exhibited no proteolytic processing whereas the mutant forms of sis-E1 exhibited normal proteolytic processing. Treatment with suramin, a polyanionic compound that disrupts ligand/receptor interactions at the cell surface, was able to revert the transformed phenotype induced by the mutant sis-E1 constructs described here. Our results demonstrate that autocrine interactions between the v-sis oncoprotein and PDGF receptors within the early Golgi complex do not result in functional signal transduction. Another v-sis fusion protein was constructed by attaching the transmembrane domain and COOH-terminus of TGN38, a protein that localizes to the trans-Golgi network (TGN). This construct was primarily retained intracellularly, although some of the fusion protein reached the surface. Deletion of the COOH-terminal region of the TGN38 retention signal abrogated the TGN-localization, as evidenced by very prominent cell surface localization, and resulted in increased transforming activity. The behavior of the sis-TGN38 derivatives is discussed within the context of the properties of TGN38 itself, which is known to recycle from the cell surface to the TGN.",1994 Dec 2,,J Cell Biol,,,True
e14c267f2323c8a137e2698dcf29a87713898166,PMC,"Localization of the Lys, Asp, Glu, Leu tetrapeptide receptor to the Golgi complex and the intermediate compartment in mammalian cells",,PMC2120279,7798312,CC BY-NC-SA,"The carboxyl-terminal Lys-Asp-Glu-Leu (KDEL), or a closely-related sequence, is important for ER localization of both lumenal as well as type II membrane proteins. This sequence functions as a retrieval signal at post-ER compartment(s), but the exact compartment(s) where the retrieval occurs remains unresolved. With an affinity-purified antibody against the carboxyl-terminal sequence of the mammalian KDEL receptor, we have investigated its subcellular localization using immunogold labeling on thawed cryosections of different tissues, such as mouse spermatids and rat pancreas, as well as HeLa, Vero, NRK, and mouse L cells. We show that rab1 is an excellent marker of the intermediate compartment, and we use this marker, as well as budding profiles of the mouse hepatitis virus (MHV) in cells infected with this virus, to identify this compartment. Our results demonstrate that the KDEL receptor is concentrated in the intermediate compartment, as well as in the Golgi stack. Lower but significant labeling was detected in the rough ER. In general, only small amounts of the receptor were detected on the trans side of the Golgi stack, including the trans- Golgi network (TGN) of normal cells and tissues. However, some stress conditions, such as infection with vaccinia virus or vesicular stomatitis virus, as well as 20 degrees C or 43 degrees C treatment, resulted in a significant shift of the distribution towards the trans- TGN side of the Golgi stack. This shift could be quantified in HeLa cells stably expressing a TGN marker. No significant labeling was detected in structures distal to the TGN under all conditions tested. After GTP gamma S treatment of permeabilized cells, the receptor was detected in the beta-COP-containing buds/vesicles that accumulate after this treatment, suggesting that these vesicles may transport the receptor between compartments. We propose that retrieval of KDEL- containing proteins occurs at multiple post-ER compartments up to the TGN along the exocytotic pathway, and that within this pathway, the amounts of the receptor in different compartments varies according to physiological conditions.",1994 Dec 2,,J Cell Biol,,,True
6050d0c1b7c6990972e6cdfca89f79745b13cc14,PMC,Targeting of protein ERGIC-53 to the ER/ERGIC/cis-Golgi recycling pathway,,PMC2120588,7559786,CC BY-NC-SA,"ERGIC-53 is a lectin-type membrane protein that continuously recycles between the ER, ER-Golgi intermediate compartment (ERGIC) and the cis- Golgi. To identify the targeting signals that mediate this recycling, N- glycosylated and myc-tagged variants of ERGIC-53 were constructed. By monitoring endoglycosidase H resistance, we measured the loss from the ER-ERGIC-cis-Golgi cycle of ERGIC-53. A domain exchange approach with the plasma membrane reporter protein CD4 showed that the transmembrane and the lumenal domains are not sufficient, while the cytoplasmic domain of ERGIC-53 is required and sufficient for pre-medial-Golgi localization. However, the ERGIC-53 cytoplasmic domain on CD4 lead to increased ER-staining by immunofluorescence microscopy indicating that this domain alone cannot provide for unbiased recycling through the ER- ERGIC-cis-Golgi compartments. Complete progress through the ER-ERGIC- cis-Golgi recycling pathway requires the cytoplasmic domain acting together with the lumenal domain of ERGIC-53. Dissection of the cytoplasmic domain revealed a COOH-terminal di-lysine ER-retrieval signal, KKFF, and an RSQQE targeting determinant adjacent to the transmembrane domain. Surprisingly, the two COOH-terminal phenylalanines influence the targeting. They reduce the ER-retrieval capacity of the di-lysine signal and modulate the RSQQE determinant.",1995 Oct 1,,J Cell Biol,,,True
bfaf24a34273d866bfa8ca32accf91d6a928c163,PMC,"Localization of a yeast early Golgi mannosyltransferase, Och1p, involves retrograde transport",,PMC2120767,8601597,CC BY-NC-SA,"To analyze the mechanism of integral membrane protein localization in the early Golgi apparatus of Saccharomyces cerevisiae, we have used Och1p, a cis-Golgi mannosyltransferase. A series of influenza virus hemagglutinin (HA) epitope-tagged fusion proteins was constructed in which invertase is appended to the Golgi-luminal carboxy terminus of full-length Och1p. Several constructs included a Kex2p cleavage site between the Och1p and invertase moieties to monitor transit to the Kex2p-containing TGN. Cells expressing an Och1p-invertase fusion do not secrete invertase, but those expressing an Och1p-Kex2p site-invertase fusion protein secrete high levels of invertase in a Kex2p-dependent manner. The Och1p-Kex2p site-invertase fusion protein is cleaved with a half-time of 5 min, and the process proceeds to completion. Before cleavage the protein receives glycosyl modifications indicative of passage through the medial- and trans-Golgi, therefore cleavage occurs after ordered anterograde transport through the Golgi to the TGN. Transit to distal compartments is not induced by the invertase moiety, since noninvertase fusion constructs encounter the same glycosyltransferases and Kex2p as well. The Och1p-HA moiety, irrespective of whether it is generated by cleavage of the fusion protein in the TGN or synthesized de novo, is degraded with a half-time of about 60 min. Thus, the half-time of degradation is 12-fold longer than the time required to reach the TGN. At steady state, de novo- synthesized and TGN-generated HA epitope-tagged Och1p reside in a compartment with a buoyant density identical to that of wild-type Och1p and distinct from that of the vacuole or the TGN. Finally, och1 null cells that express an Ochlp fusion construct known to rapidly encounter the TGN glycosylate invertase to the same extent as wild-type cells, indicating that they have phenotypically wild-type Och1p activity. These results lead us to propose a model for Och1p-HA localization that involves movement to distal compartments, at least as far as the TGN, followed by retrieval to the cis compartment, presumably by vesicular transport.",1996 Mar 2,,J Cell Biol,,,True
2a771153af1b6fd5e71dc23f5db7c83bb5a3f231,PMC,Endoplasmic reticulum localization of Sec12p is achieved by two mechanisms: Rer1p-dependent retrieval that requires the transmembrane domain and Rer1p-independent retention that involves the cytoplasmic domain,,PMC2120888,8707815,CC BY-NC-SA,"Yeast Sec12p is a type II transmembrane protein in the ER, which is essential for the formation of transport vesicles. From biochemical and morphological lines of evidence, we have proposed that Sec12p is localized to the ER by two mechanisms: static retention in the ER and dynamic retrieval from the early Golgi compartment. We have also shown that Rer1p, a membrane protein in the Golgi, is required for correct localization of Sec12p. In the present study, we have performed a systematic analysis to determine the ER localization signals in Sec12p corresponding to these two mechanisms. Both the transmembrane domain (TMD) and the NH2-terminal cytoplasmic domain of Sec12p show the ability to localize the protein to the ER. The effect of the TMD is potent and sufficient by itself for the ER localization and is strongly dependent on Rer1p. On the other hand, the cytoplasmic domain shows a moderate ER-localization capability which is independent of Rer1p. The rate of mannosyl modification has been measured to distinguish between retention and retrieval. The cytoplasmic domain significantly delays the transport from the ER to the cis-Golgi. In contrast, the TMD shows only a subtle retardation in the transport from the ER to the cis-Golgi but strictly prevents the transport beyond there. From these observations, we conclude that the TMD mainly acts as the retrieval signal and the cytoplasmic domain contains the retention signal. This study not only supports the two-mechanisms hypothesis but also provides powerful tools to dissect the two.",1996 Jul 2,,J Cell Biol,,,True
077d5a9302762a66842c6bdf13912433954ca723,PMC,The organization of endoplasmic reticulum export complexes,,PMC2121027,8858160,CC BY-NC-SA,"Export of cargo from the ER occurs through the formation of 60-70nm COPII-coated vesicular carriers. We have applied serial-thin sectioning and stereology to quantitatively characterize the three-dimensional organization of ER export sites in vivo and in vitro. We find that ER buds in vivo are nonrandomly distributed, being concentrated in regional foci we refer to as export complexes. The basic organization of an export complex can be divided into an active COPII-containing budding zone on a single ER cisterna, which is adjacent to budding zones found on distantly connected ER cisternae. These budding foci surround and face a central cluster of morphologically independent vesicular-tubular elements that contain COPI coats involved in retrograde transport. Vesicles within these export complexes contain concentrated cargo molecules. The structure of vesicular-tubular clusters in export complexes is particularly striking in replicas generated using a quick-freeze, deep-etch approach to visualize for the first time their three-dimensional organization and cargo composition. We conclude that budding from the ER through recruitment of COPII is confined to highly specialized export complexes that topologically restrict anterograde transport to regional foci to facilitate efficient coupling to retrograde recycling by COPI.",1996 Oct 1,,J Cell Biol,,,True
3e2e2a0b86f45e26fbd4724a26d74b62a5f7b0e3,PMC,A pathway for targeting soluble misfolded proteins to the yeast vacuole,,PMC2121066,8909538,CC BY-NC-SA,"We have evaluated the fate of misfolded protein domains in the Saccharomyces cerevisiae secretory pathway by fusing mutant forms of the NH2-terminal domain of lambda repressor protein to the secreted protein invertase. The hybrid protein carrying the wild-type repressor domain is mostly secreted to the cell surface, whereas hybrid proteins with amino acid substitutions that cause the repressor domain to be thermodynamically unstable are retained intracellularly. Surprisingly, the retained hybrids are found in the vacuole, where the repressor moiety is degraded by vacuolar proteases. The following observations indicate that receptor-mediated recognition of the mutant repressor domain in the Golgi lumen targets these hybrid fusions to the vacuole. (a) The invertase-repressor fusions, like wild-type invertase, behave as soluble proteins in the ER lumen. (b) Targeting to the vacuole is saturable since overexpression of the hybrids carrying mutant repressor increases the fraction of fusion protein that appears at the cell surface. (c) Finally, deletion of the VPS10 gene, which encodes the transmembrane Golgi receptor responsible for targeting carboxypeptidase Y to the vacuole, causes the mutant hybrids to be diverted to the cell surface. Together these findings suggest that yeast have a salvage pathway for degradation of nonnative luminal proteins by receptor- mediated transport to the vacuole.",1996 Nov 1,,J Cell Biol,,,True
3b8ec6abf589bfc9738475e02cb3a6d18eaba5b7,PMC,Protective immune responses against West Nile virus are primed by distinct complement activation pathways,http://dx.doi.org/10.1084/jem.20052388,PMC2121216,16651386,CC BY-NC-SA,"West Nile virus (WNV) causes a severe infection of the central nervous system in several vertebrate animals including humans. Prior studies have shown that complement plays a critical role in controlling WNV infection in complement (C) 3(−/−) and complement receptor 1/2(−/−) mice. Here, we dissect the contributions of the individual complement activation pathways to the protection from WNV disease. Genetic deficiencies in C1q, C4, factor B, or factor D all resulted in increased mortality in mice, suggesting that all activation pathways function together to limit WNV spread. In the absence of alternative pathway complement activation, WNV disseminated into the central nervous system at earlier times and was associated with reduced CD8(+) T cell responses yet near normal anti-WNV antibody profiles. Animals lacking the classical and lectin pathways had deficits in both B and T cell responses to WNV. Finally, and somewhat surprisingly, C1q was required for productive infection in the spleen but not for development of adaptive immune responses after WNV infection. Our results suggest that individual pathways of complement activation control WNV infection by priming adaptive immune responses through distinct mechanisms.",2006 May 15,"['Mehlhop, Erin', 'Diamond, Michael S.']",J Exp Med,,,True
46c58d9482fd8d00108402c45033131561eb8921,PMC,A Transfected Sialyltransferase That Is Elevated in Breast Cancer and Localizes to the medial/trans-Golgi Apparatus Inhibits the Development of core-2–based O-Glycans,,PMC2132526,9182658,CC BY-NC-SA,"The α2,3 sialyltransferase, α2,3 SAT (O), catalyzes the transfer of sialic acid to Galβ1,3 N-acetyld-galactosamine (GalNAc) (core-1) in mucin type O-glycosylation, and thus terminates chain extension. A Core-2 branch can also be formed from core-1 by the core-2 β1,6 N-acetyl-d-glucosamine transferase (β1,6 GlcNAc T) that leads to chain extension. Increased levels of the α2,3 SAT (O) and decreased levels of the core-2 β1,6 GlcNAc T are seen in breast cancer cells and correlate with differences in the structure of the O-glycans synthesized (Brockhausen et al., 1995; Lloyd et al., 1996). Since in mucin type O-glycosylation sugars are added individually and sequentially in the Golgi apparatus, the position of the transferases, as well as their activity, can determine the final structure of the O-glycans synthesized. A cDNA coding for the human α2,3 SAT (O) tagged with an immunoreactive epitope from the myc gene has been used to map the position of the glycosyltransferase in nontumorigenic (MTSV1-7) and malignant (T47D) breast epithelial cell lines. Transfectants were analyzed for expression of the enzyme at the level of message and protein, as well as for enzymic activity. In T47D cells, which do not express core-2 β1,6 GlcNAc T, the increased activity of the sialyltransferase correlated with increased sialylation of core-1 O-glycans on the epithelial mucin MUC1. Furthermore, in MTSV1-7 cells, which do express core-2 β1,6 GlcNAc T, an increase in sialylated core-1 structures is accompanied by a reduction in the ratio of GlcNAc: GalNAc in the O-glycans attached to MUC1, implying a decrease in branching. Using quantitative immunoelectron microscopy, the sialyltransferase was mapped to the medial- and trans-Golgi cisternae, with some being present in the TGN. The data represent the first fine mapping of a sialyltransferase specifically active in O-glycosylation and demonstrate that the structure of O-glycans synthesized by a cell can be manipulated by transfecting with recombinant glycosyltransferases.",1997 Jun 16,"['Whitehouse, Caroline', 'Burchell, Joy', 'Gschmeissner, Stephen', 'Brockhausen, Inka', 'Lloyd, Kenneth O.', 'Taylor-Papadimitriou, Joyce']",J Cell Biol,,,True
f39b51bbd9ece044b1af4f83b6ff05053810e7d9,PMC,"Ceramide Accumulation Uncovers a Cycling Pathway for the cis-Golgi Network Marker, Infectious Bronchitis Virus M Protein",,PMC2132625,9396747,CC BY-NC-SA,"The M glycoprotein from the avian coronavirus, infectious bronchitis virus (IBV), contains information for localization to the cis-Golgi network in its first transmembrane domain. We hypothesize that localization to the Golgi complex may depend in part on specific interactions between protein transmembrane domains and membrane lipids. Because the site of sphingolipid synthesis overlaps the localization of IBV M, we asked whether perturbation of sphingolipids affected localization of IBV M. Short-term treatment with two inhibitors of sphingolipid synthesis had no effect on localization of IBV M or other Golgi markers. Thus, ongoing synthesis of these lipids was not required for proper localization. Surprisingly, a third inhibitor, d,l-threo-1-phenyl-2-decanoylamino-3-morpholino- 1-propanol (PDMP), shifted the steady-state distribution of IBV M from the Golgi complex to the ER. This effect was rapid and reversible and was also observed for ERGIC-53 but not for Golgi stack proteins. At the concentration of PDMP used, conversion of ceramide into both glucosylceramide and sphingomyelin was inhibited. Pretreatment with upstream inhibitors partially reversed the effects of PDMP, suggesting that ceramide accumulation mediates the PDMP-induced alterations. Indeed, an increase in cellular ceramide was measured in PDMP-treated cells. We propose that IBV M is at least in part localized by retrieval mechanisms. Further, ceramide accumulation reveals this cycle by upsetting the balance of anterograde and retrograde traffic and/ or disrupting retention by altering bilayer dynamics.",1997 Dec 15,"['Maceyka, Michael', 'Machamer, Carolyn E.']",J Cell Biol,,,True
92a4cbcc55d992b5fd6f9c77de0fb4f5030a566a,PMC,Specific Single or Double Proline Substitutions in the “Spring-loaded” Coiled-Coil Region of the Influenza Hemagglutinin Impair or Abolish Membrane Fusion Activity,,PMC2132786,9628890,CC BY-NC-SA,"We tested the role of the “spring-loaded” conformational change in the fusion mechanism of the influenza hemagglutinin (HA) by assessing the effects of 10 point mutants in the region of high coiled-coil propensity, HA2 54–81. The mutants included proline substitutions at HA2 55, 71, and 80, as well as a double proline substitution at residues 55 and 71. Mutants were expressed in COS or 293T cells and assayed for cell surface expression and structural features as well as for their ability to change conformation and induce fusion at low pH. We found the following: Specific mutations affected the precise carbohydrate structure and folding of the HA trimer. All of the mutants, however, formed trimers that could be expressed at the cell surface in a form that could be proteolytically cleaved from the precursor, HA0, to the fusion-permissive form, HA1-S-S-HA2. All mutants reacted with an antibody against the major antigenic site and bound red blood cells. Seven out of ten mutants displayed a wild-type (wt) or moderately elevated pH dependence for the conformational change. V55P displayed a substantial reduction (∼60– 80%) in the initial rate of lipid mixing. The other single mutants displayed efficient fusion with the same pH dependence as wt-HA. The double proline mutant V55P/ S71P displayed no fusion activity despite being well expressed at the cell surface as a proteolytically cleaved trimer that could bind red blood cells and change conformation at low pH. The impairment in fusion for both V55P and V55P/S71P was at the level of outer leaflet lipid mixing. We interpret our results in support of the hypothesis that the spring-loaded conformational change is required for fusion. An alternate model is discussed.",1998 Jun 15,"['Qiao, Hui', 'Pelletier, Sandra L.', 'Hoffman, Lucas', 'Hacker, Jill', 'Armstrong, R. Todd', 'White, Judith M.']",J Cell Biol,,,True
f342d276133084c4e742dfa29ee97481fc03e7f7,PMC,An Unconventional Role for Cytoplasmic Disulfide Bonds in Vaccinia Virus Proteins,,PMC2132897,9922453,CC BY-NC-SA,"Previous data have shown that reducing agents disrupt the structure of vaccinia virus (vv). Here, we have analyzed the disulfide bonding of vv proteins in detail. In vv-infected cells cytoplasmically synthesized vv core proteins became disulfide bonded in the newly assembled intracellular mature viruses (IMVs). vv membrane proteins also assembled disulfide bonds, but independent of IMV formation and to a large extent on their cytoplasmic domains. If disulfide bonding was prevented, virus assembly was only partially impaired as shown by electron microscopy as well as a biochemical assay of IMV formation. Under these conditions, however, the membranes around the isolated particles appeared less stable and detached from the underlying core. During the viral infection process the membrane proteins remained disulfide bonded, whereas the core proteins were reduced, concomitant with delivery of the cores into the cytoplasm. Our data show that vv has evolved an unique system for the assembly of cytoplasmic disulfide bonds that are localized both on the exterior and interior parts of the IMV.",1999 Jan 25,"['Locker, Jacomine Krijnse', 'Griffiths, Gareth']",J Cell Biol,,,True
ed836dbe62d537006fc207428b489d208836a949,PMC,Targeting of Moloney murine leukemia virus gag precursor to the site of virus budding,,PMC2133957,8991095,CC BY-NC-SA,"Retrovirus Moloney murine leukemia virus (M-MuLV) matures by budding at the cell surface. Central to the budding process is the myristoylated viral core protein precursor Gag which, even in the absence of all other viral components, is capable of associating with the cytoplasmic leaflet of the plasma membrane and assembling into extracellular virus- like particles. In this paper we have used heterologous, Semliki Forest virus-driven, expression of M-MuLV Gag to study the mechanism by which this protein is targeted to the cell surface. In pulse-chase experiments, BFA, monensin, and 20 degrees C block did not affect incorporation of Gag into extracellular particles thereby indicating that the secretory pathway is not involved in targeting of Gag to the cell surface. Subcellular fractionation studies demonstrated that newly synthesized Gag became rapidly and efficiently associated with membranes which had a density similar to that of plasma membrane- derived vesicles. Protease-protection studies confirmed that the Gag- containing membranes were of plasma membrane origin, since in crude cell homogenates, the bulk of newly synthesized Gag was protease- resistant as expected of a protein that binds to the cytoplasmic leaflet of the plasma membrane. Taken together these data indicate that targeting of M-MuLV Gag to the cell surface proceeds via direct insertion of the protein to the cytoplasmic side of the plasma membrane. Furthermore, since the membrane insertion reaction is highly efficient and specific, this suggests that the reaction is dependent on as-yet-unidentified cellular factors.",1996 Dec 2,,J Cell Biol,,,True
8f64ab87b255d034c48a5a7c8a8a82a4ea81e67b,PMC,Two Separate Signals Act Independently to Localize a Yeast Late Golgi Membrane Protein through a Combination of Retrieval and Retention,,PMC2134822,9015300,CC BY-NC-SA,"The localization of proteins to late-Golgi membranes (TGN) of Saccharomyces cerevisiae is conferred by targeting motifs containing aromatic residues in the cytosolic domains of these proteins. These signals could act by directing retrieval from a post-Golgi compartment or by preventing exit from the TGN. To investigate the mechanism of localization of yeast TGN proteins, we used the heterologous protein A-ALP (consisting of the cytosolic domain of dipeptidyl aminopeptidase A [DPAP A] fused to the transmembrane and luminal domains of the vacuolar protein alkaline phosphatase [ALP]), which localizes to the yeast TGN. Insertion of the aromatic residue–based TGN localization motif (FXFXD) of DPAP A into the cytosolic domain of ALP results in a protein that resides in the TGN. We demonstrate that the FXFXD motif confers Golgi localization through retrieval from a post-Golgi compartment by detecting a post-Golgi processed form of this protein in the TGN. We present an assay that uncouples retrieval-mediated Golgi localization from static retention-based localization, allowing measurement of the rate at which proteins exit the yeast TGN. We also demonstrate that the cytosolic domain of DPAP A contains additional information, separate from the retrieval motif, that slows exit from the TGN. We propose a model for DPAP A localization that involves two distinct mechanisms: one in which the FXFXD motif directs retrieval from a post-Golgi compartment, and a second that slows the rate at which DPAP A exits the TGN.",1997 Jan 27,"['Bryant, Nia J.', 'Stevens, Tom H.']",J Cell Biol,,,True
341b4e78cf80dacd62c031f96ff716fff728deb9,PMC,ACUTE HEPATITIS ASSOCIATED WITH MOUSE LEUKEMIA : V. THE NEUROTROPIC PROPERTIES OF THE CAUSAL VIRUS,,PMC2136532,13271673,CC BY-NC-SA,"Observations on the behavior of MHV (Pr) in the cerebral tissue of Princeton and Swiss weanling mice indicated a limited neurotropism. The virus migrated to the brain on intraperitoneal injection and was established there by cranial passage, though with difficulty in Swiss mice. Intracerebral multiplication was rarely followed by outward signs of nervous disorder. A slight pathologic reaction occurred in the brains of intracerebrally injected Princeton mice, but it was negligible compared with that of the ensuing hepatitis. In Swiss mice, injected intracerebrally with a mixture of MHV (Pr) and Eperythrozoon coccoides, a related virus with restricted pathogenicity and host range, possibly a mutant, was isolated from the liver and brain. MHV (C), an actively hepatotropic virus recovered from leukemic Balb C mice, was much more neurotropic than MHV (Pr). Intracerebral injection of Balb C and Swiss weanling mice was attended by marked leptomeningeal and encephalitic lesions. Paralysis of the extremities occurred in some of the animals. The virus was essentially inactive in Princeton mice. During the intracerebral passage of MHV (C) in Swiss mice a pleuropneumonia-like organism was isolated from the brain. In conjunction with the virus this organism produced a vigorous leukocytic reaction.",1955 Oct 31,"Nelson, John B.",J Exp Med,,,False
0a19aacc124c9c42d66d481a9d0c837a76a252e6,PMC,THE ENHANCING EFFECT OF MURINE HEPATITIS VIRUS ON THE CEREBRAL ACTIVITY OF PLEUROPNEUMONIA-LIKE ORGANISMS IN MICE,,PMC2136741,13449230,CC BY-NC-SA,"Pleuropneumoma-like organisms (PPLO) of the catarrhal type were isolated from the brain of a Swiss mouse during the cranial passage of mouse hepatitis virus-MHV(C). Cranial injection of the PPLO alone in Swiss and Princeton weanlings was attended by a meagre growth of the organisms in the brain, with no pathologic change. The growth of both catarrhal and conjunctival strains of PPLO in the brains of Swiss mice was greatly enhanced by the simultaneous injection of MHV(C). Rolling was not a characteristic sign prior to autopsy. Brain sections regularly showed a vigorous leukocytic response, commonly accompanied by the destruction of nerve cells in the anterior horns of the cerebrum. Injected in Princeton mice together with the virus, the organisms barely survived and were inactive. MHV(Pr) enhanced the growth and pathogenicity of PPLO in the brains of Princeton mice but failed to do so in Swiss. The behavior of PPLO in the brain was likewise affected by the presence of agar, as earlier observed by Findlay et al. In comparison with the effect of MHV, the enhancement was reduced in rate in both strains of mice and was not accompanied by outward signs of nervous disorder. Hydrocephalus which often followed injection of the PPLO-agar mixture was also produced by agar-bouillon alone.",1957 Aug 1,"Nelson, John B.",J Exp Med,,,True
e24e6736123c670928dd233196d473f81e998b24,PMC,THE CELLULAR NATURE OF GENETIC SUSCEPTIBILITY TO A VIRUS,,PMC2137639,14030664,CC BY-NC-SA,"Using peritoneal macrophage cultures it was found that both PRI mice and their macrophages in culture were susceptible to mouse hepatitis virus and that C(3)H mice and macrophages were resistant. All F(1) macrophages and some back-cross cell cultures were susceptible. The degeneration of F(1) and back-cross macrophages obtained either from adult mouse peritoneal exudate or newborn mouse liver, occurred more slowly than PRI macrophages. Segregation of susceptibility occurred in the first back-cross generation. Tests of three back-cross generations from susceptible mice yielded about one-quarter of the mice shown to be susceptible either by direct test or test of their macrophages. A clear correlation between susceptibility in vivo and in vitro was established both in the test of the percentage segregation and in tests of individual back-cross mice. A small series of tests, however, indicated that 50 per cent of the back-cross mice had the genetic capacity to transmit susceptibility. Thus a hypothesis of two genes for susceptibility, although not excluded, may yield to a hypothesis of a single dominant gene, incompletely expressed. Resistant cells were converted into susceptible cells by ingestion of a relatively large particle containing a heat-stable substance. This susceptibility, although complete, was temporary. The nature of the factor causing the change has been discussed.",1963 May 1,"['Kantoch, M.', 'Warwick, A.', 'Bang, F. B.']",J Exp Med,,,True
1863b855d1e87b1a2b85a88c71c0b8753619f0b2,PMC,Novel Genes Involved in Endosomal Traffic in Yeast Revealed by Suppression of a Targeting-defective Plasma Membrane ATPase Mutant,,PMC2138039,9265642,CC BY-NC-SA,"A novel genetic selection was used to identify genes regulating traffic in the yeast endosomal system. We took advantage of a temperature-sensitive mutant in PMA1, encoding the plasma membrane ATPase, in which newly synthesized Pma1 is mislocalized to the vacuole via the endosome. Diversion of mutant Pma1 from vacuolar delivery and rerouting to the plasma membrane is a major mechanism of suppression of pma1(ts). 16 independent suppressor of pma1 (sop) mutants were isolated. Identification of the corresponding genes reveals eight that are identical with VPS genes required for delivery of newly synthesized vacuolar proteins. A second group of SOP genes participates in vacuolar delivery of mutant Pma1 but is not essential for delivery of the vacuolar protease carboxypeptidase Y. Because the biosynthetic pathway to the vacuole intersects with the endocytic pathway, internalization of a bulk membrane endocytic marker FM 4-64 was assayed in the sop mutants. By this means, defective endosome-to-vacuole trafficking was revealed in a subset of sop mutants. Another subset of sop mutants displays perturbed trafficking between endosome and Golgi: impaired pro-α factor processing in these strains was found to be due to defective recycling of the trans-Golgi protease Kex2. One of these strains defective in Kex2 trafficking carries a mutation in SOP2, encoding a homologue of mammalian synaptojanin (implicated in synaptic vesicle endocytosis and recycling). Thus, cell surface delivery of mutant Pma1 can occur as a consequence of disturbances at several different sites in the endosomal system.",1997 Aug 25,"['Luo, Wen-jie', 'Chang, Amy']",J Cell Biol,,,True
03afd58d8d29e1c6d008e06e38553079bbdc4d02,PMC,ONTOGENY OF MACROPHAGE RESISTANCE TO MOUSE HEPATITIS IN VIVO AND IN VITRO,,PMC2138373,4289738,CC BY-NC-SA,"Adult or weanling C(3)H mice were found to be genetically resistant to a strain of mouse hepatitis virus. Infant C(3)H mice, however, developed infection and died from mouse hepatitis virus when minimal infectious doses of virus were given to them. There was a delay in the time of death compared to that of the genetically susceptible strain, and the virus recovered from these mice had increased pathogenicity for C(3)H mice. The ontogeny of resistance to hepatitis in the C(3)H mice thus progresses from delayed susceptibility to complete resistance as the age of the host increases. It is reflected in increased resistance of macrophages derived in vitro from liver cultures of infant mice of different ages. This increase in resistance with age was reduced by maintaining the cultures for a longer period of time before inoculation, or by increasing the number of explants in a given culture. Resistant cells were uniformly furnished by mice age 16 days, or more. It is concluded that a process of maturation of resistance of the cells takes place after the mice are born, but that this does not continue under in vitro conditions, and that it may be modified by the environment of the cells.",1967 Mar 31,"['Gallily, Ruth', 'Warwick, Anne', 'Bang, Frederik B.']",J Exp Med,,,True
157d6b204fdc9b7ea26cdbffea19197b0faaa31f,PMC,IN VITRO INTERACTION OF MOUSE HEPATITIS VIRUS AND MACROPHAGES FROM GENETICALLY RESISTANT MICE : II. BIOLOGICAL CHARACTERIZATION OF A VARIANT VIRUS MHV(C(3)H) ISOLATED FROM STOCKS OF MHV(PRI),,PMC2138776,4317220,CC BY-NC-SA,"A variant mouse hepatitis virus MHV(C(3)H) to which cultured peritoneal macrophages from both PRI and C(3)H mice were susceptible was isolated from stocks of the MHV(PRI) strain of mouse hepatitis virus. It was cloned on C(3)H macrophage monolayers and killed both adult PRI and C(3)H mice when injected intraperitoneally. This new variant was antigenically indistinguishable from the wild type virus. While the emergence of the variant virus was delayed in the course of infecting C(3)H macrophages with large inocula of MHV(PRI), the second passage grew to a high titer in both cell types without delay. Thus, adaptation to the new host was immediate. Interference, apparently not interferon-mediated, between the two variant viruses may have been the cause for the delay in the emergence of the variant virus. The delayed destruction of C(3)H-cultured macrophages by large inocula of MHV(PRI) uniformly resulted in the emergence of MHV(C(3)H). Whether the new variant emerged as a result of a selection of a pre-existing stable mutant or was conditioned by ""growth"" in the resistant host was not determined.",1970 Mar 31,"['Shif, Ilan', 'Bang, Frederik B.']",J Exp Med,,,True
687611906b82bcee9941de1cf6543e8e7871da06,PMC,IN VITRO INTERACTION OF MOUSE HEPATITIS VIRUS AND MACROPHAGES FROM GENETICALLY RESISTANT MICE : I. ADSORPTION OF VIRUS AND GROWTH CURVES,,PMC2138781,4317219,CC BY-NC-SA,"Peritoneal macrophages from genetically resistant C(3)H mice and genetically susceptible Princeton (PRI) mice adsorbed the MHV (PRI) strain of mouse hepatitis virus equally well. The difference between the permissive cells and the nonpermissive ones seems to reside in the ability of the former to ""eclipse"" the virus and, subsequently, support virus replication. C(3)H cells exposed to low multiplicities of the virus remained intact with no demonstrable viral replication. Virus, taken up by the resistant cells, was protected from heat and underwent slow inactivation while few or no virus particles were released into the medium.",1970 Mar 31,"['Shif, Ilan', 'Bang, Frederik B.']",J Exp Med,,,True
ccfba5ba6e11eff35a72dead3fac7f7daebda11d,PMC,"Mannose 6–Phosphate Receptors Are Sorted from Immature Secretory Granules via Adaptor Protein AP-1, Clathrin, and Syntaxin 6–positive Vesicles",,PMC2148452,9548715,CC BY-NC-SA,"The occurrence of clathrin-coated buds on immature granules (IGs) of the regulated secretory pathway suggests that specific transmembrane proteins are sorted into these buds through interaction with cytosolic adaptor proteins. By quantitative immunoelectron microscopy of rat endocrine pancreatic β cells and exocrine parotid and pancreatic cells, we show for the first time that the mannose 6–phosphate receptors (MPRs) for lysosomal enzyme sorting colocalize with the AP-1 adaptor in clathrin-coated buds on IGs. Furthermore, the concentrations of both MPR and AP-1 decline by ∼90% as the granules mature. Concomitantly, in exocrine secretory cells lysosomal proenzymes enter and then are sorted out of IGs, just as was previously observed in β cells (Kuliawat, R., J. Klumperman, T. Ludwig, and P. Arvan. 1997. J. Cell Biol. 137:595–608). The exit of MPRs in AP-1/clathrin-coated buds is selective, indicated by the fact that the membrane protein phogrin is not removed from maturing granules. We have also made the first observation of a soluble N-ethylmaleimide–sensitive factor attachment protein receptor, syntaxin 6, which has been implicated in clathrin-coated vesicle trafficking from the TGN to endosomes (Bock, J.B., J. Klumperman, S. Davanger, and R.H. Scheller. 1997. Mol. Biol. Cell. 8:1261–1271) that enters and then exits the regulated secretory pathway during granule maturation. Thus, we hypothesize that during secretory granule maturation, MPR–ligand complexes and syntaxin 6 are removed from IGs by AP-1/clathrin-coated vesicles, and then delivered to endosomes.",1998 Apr 20,"['Klumperman, Judith', 'Kuliawat, Regina', 'Griffith, Janice M.', 'Geuze, Hans J.', 'Arvan, Peter']",J Cell Biol,,,True
8931fabdc25094445ab2450c3a5117dab632e868,PMC,Cooh-Terminal Truncations Promote Proteasome-Dependent Degradation of Mature Cystic Fibrosis Transmembrane Conductance Regulator from Post-Golgi Compartments,,PMC2174331,11381082,CC BY-NC-SA,"Impaired biosynthetic processing of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), a cAMP-regulated chloride channel, constitutes the most common cause of CF. Recently, we have identified a distinct category of mutation, caused by premature stop codons and frameshift mutations, which manifests in diminished expression of COOH-terminally truncated CFTR at the cell surface. Although the biosynthetic processing and plasma membrane targeting of truncated CFTRs are preserved, the turnover of the complex-glycosylated mutant is sixfold faster than its wild-type (wt) counterpart. Destabilization of the truncated CFTR coincides with its enhanced susceptibility to proteasome-dependent degradation from post-Golgi compartments globally, and the plasma membrane specifically, determined by pulse–chase analysis in conjunction with cell surface biotinylation. Proteolytic cleavage of the full-length complex-glycosylated wt and degradation intermediates derived from both T70 and wt CFTR requires endolysosomal proteases. The enhanced protease sensitivity in vitro and the decreased thermostability of the complex-glycosylated T70 CFTR in vivo suggest that structural destabilization may account for the increased proteasome susceptibility and the short residence time at the cell surface. These in turn are responsible, at least in part, for the phenotypic manifestation of CF. We propose that the proteasome-ubiquitin pathway may be involved in the peripheral quality control of other, partially unfolded membrane proteins as well.",2001 May 28,"['Benharouga, Mohamed', 'Haardt, Martin', 'Kartner, Norbert', 'Lukacs, Gergely L.']",J Cell Biol,,,True
671f008a0c8884f741c6500eb243db4d06391004,PMC,"Pex19 Binds Multiple Peroxisomal Membrane Proteins, Is Predominantly Cytoplasmic, and Is Required for Peroxisome Membrane Synthesis",,PMC2174547,10704444,CC BY-NC-SA,"Peroxisomes are components of virtually all eukaryotic cells. While much is known about peroxisomal matrix protein import, our understanding of how peroxisomal membrane proteins (PMPs) are targeted and inserted into the peroxisome membrane is extremely limited. Here, we show that PEX19 binds a broad spectrum of PMPs, displays saturable PMP binding, and interacts with regions of PMPs required for their targeting to peroxisomes. Furthermore, mislocalization of PEX19 to the nucleus leads to nuclear accumulation of newly synthesized PMPs. At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of the protein in the cytoplasm. We propose that PEX19 may bind newly synthesized PMPs and facilitate their insertion into the peroxisome membrane. This hypothesis is supported by the observation that the loss of PEX19 results in degradation of PMPs and/or mislocalization of PMPs to the mitochondrion.",2000 Mar 6,"['Sacksteder, Katherine A.', 'Jones, Jacob M.', 'South, Sarah T.', 'Li, Xiaoling', 'Liu, Yifei', 'Gould, Stephen J.']",J Cell Biol,,,True
63c64ba93501a9ec60ab113b55c23d5bc602a13c,PMC,A bioinformatic filter for improved base-call accuracy and polymorphism detection using the Affymetrix GeneChip® whole-genome resequencing platform,http://dx.doi.org/10.1093/nar/gkm918,PMC2175352,18006572,CC BY-NC,"DNA resequencing arrays enable rapid acquisition of high-quality sequence data. This technology represents a promising platform for rapid high-resolution genotyping of microorganisms. Traditional array-based resequencing methods have relied on the use of specific PCR-amplified fragments from the query samples as hybridization targets. While this specificity in the target DNA population reduces the potential for artifacts caused by cross-hybridization, the subsampling of the query genome limits the sequence coverage that can be obtained and therefore reduces the technique's resolution as a genotyping method. We have developed and validated an Affymetrix Inc. GeneChip® array-based, whole-genome resequencing platform for Francisella tularensis, the causative agent of tularemia. A set of bioinformatic filters that targeted systematic base-calling errors caused by cross-hybridization between the whole-genome sample and the array probes and by deletions in the sample DNA relative to the chip reference sequence were developed. Our approach eliminated 91% of the false-positive single-nucleotide polymorphism calls identified in the SCHU S4 query sample, at the cost of 10.7% of the true positives, yielding a total base-calling accuracy of 99.992%.",2007 Dec 15,"['Pandya, Gagan A.', 'Holmes, Michael H.', 'Sunkara, Sirisha', 'Sparks, Andrew', 'Bai, Yun', 'Verratti, Kathleen', 'Saeed, Kelly', 'Venepally, Pratap', 'Jarrahi, Behnam', 'Fleischmann, Robert D.', 'Peterson, Scott N.']",Nucleic Acids Res,,,True
20c05a8e1616b61a78300ee5911bc70bd1c952d3,PMC,Antidiabetes and Anti-obesity Activity of Lagerstroemia speciosa,http://dx.doi.org/10.1093/ecam/nem013,PMC2176148,18227906,CC BY-NC,"The leaves of Lagerstroemia speciosa (Lythraceae), a Southeast Asian tree more commonly known as banaba, have been traditionally consumed in various forms by Philippinos for treatment of diabetes and kidney related diseases. In the 1990s, the popularity of this herbal medicine began to attract the attention of scientists worldwide. Since then, researchers have conducted numerous in vitro and in vivo studies that consistently confirmed the antidiabetic activity of banaba. Scientists have identified different components of banaba to be responsible for its activity. Using tumor cells as a cell model, corosolic acid was isolated from the methanol extract of banaba and shown to be an active compound. More recently, a different cell model and the focus on the water soluble fraction of the extract led to the discovery of other compounds. The ellagitannin Lagerstroemin was identified as an effective component of the banaba extract responsible for the activity. In a different approach, using 3T3-L1 adipocytes as a cell model and a glucose uptake assay as the functional screening method, Chen et al. showed that the banaba water extract exhibited an insulin-like glucose transport inducing activity. Coupling HPLC fractionation with a glucose uptake assay, gallotannins were identified in the banaba extract as components responsible for the activity, not corosolic acid. Penta-O-galloyl-glucopyranose (PGG) was identified as the most potent gallotannin. A comparison of published data with results obtained for PGG indicates that PGG has a significantly higher glucose transport stimulatory activity than Lagerstroemin. Chen et al. have also shown that PGG exhibits anti-adipogenic properties in addition to stimulating the glucose uptake in adipocytes. The combination of glucose uptake and anti-adipogenesis activity is not found in the current insulin mimetic drugs and may indicate a great therapeutic potential of PGG.",2007 Dec 14,"['Klein, Guy', 'Kim, Jaekyung', 'Himmeldirk, Klaus', 'Cao, Yanyan', 'Chen, Xiaozhuo']",Evid Based Complement Alternat Med,,,True
b0d63875dbdde9df204257c33b47d6277c81b869,PMC,Enhancement of IgE-mediated histamine release from human basophils by viruses: role of interferon,,PMC2180621,67173,CC BY-NC-SA,"Human leukocytes maintained in culture are induced to release histamine when exposed to ragweed antigen E or anti-IgE. Leukocyte cultures incubated with virus (i.e. HSV-1, Influenza A, and Adeno-1) but not exposed to ragweed antigen E or anti-IgE fail to release histamine. If, however, leukocyte cultures are first exposed to virus and then to ragweed antigen E or anti-IgE, significant enhancement of histamine release occurs. Both infectious and inactivated virus enhance histamine release and the degree of enhancement is related to the concentration of virus and the length of the incubation. Tissue culture fluid harvested 8 h after exposure of leukocytes to virus contains a soluble factor which is capable of enhancing histamine release when added to fresh leukocyte cultures. This factor has all the properties of interferon including species specificity and cannot be dissociated from the antiviral activity of interferon. Moreover, both known inducers of interferon (poly I:poly C) and standard preparations of interferon are capable of enhancing histamine release. The enhancement of histamine release by interferon represents a new biological role for interferon.",1977 Apr 1,,J Exp Med,,,True
715fec9052e391ea2d2bd055e7fea736b2882bc7,PMC,In vitro macrophage manifestation of cortisone-induced decrease in resistance to mouse hepatitis virus,,PMC2186118,6265581,CC BY-NC-SA,"Genetically resistant G3H mice routinely yielded macrophages that were resistant when grown in 90% horse serum. These mice also routinely yielded macrophages that were susceptible to the same virus, MHV (PRI), in vitro after the mice had been treated with three intraperitoneal doses, of hydrocortisone. Dexamethasone and prednisolone when similarly administered also increased the susceptibility of C3H macrophages taken from the treated animal, but progesterone and testosterone did not. In addition, spleen cells from mice treated with cortisone made the resistant C3H macrophages 100 times more susceptible in vitro. Increased in vitro susceptibility induced in this way by hydrocortisone was reversed by exposure to supernatant fluid removed from cultures of concanavalin A-treated spleen cells.",1981 Mar 1,,J Exp Med,,,True
0b90f302993b075229dbe5f9bc03a180b2e2632f,PMC,Mouse hepatitis virus type 4 (JHM strains). induced fatal central nervous system disease. I. genetic control and murine neuron as the susceptible site of disease,,PMC2186133,6265583,CC BY-NC-SA,"Mouse hepatitis virus (JHM strain) type 4 induces acute encephalitis followed by death in many strains of laboratory mice. Immunohistochemical study in vivo and analysis of mouse neuronal cells in vitro both indicate that the target cells in this infection is the neuron. Further, examination of several inbred mouse strains and neuronal cells from them shows that disease expression is controlled by a single autosomal gene action at the level of the neuronal cell. Susceptibility is dominant but not H-2 linked. However, cultured neuronal cells and macrophages from SJL/J mice, which are resistant to this infection, fail to make significant amounts of infectious virus after an appropriate viral inoculation. Apparently the defect is not at the level of the virus-cell receptor, because these cells, in part, express viral antigens.",1981 Apr 1,,J Exp Med,,,True
ba4ec5cbbb67efa5caafb7f69b6591a83d59d3a7,PMC,Induction of monocyte procoagulant activity by murine hepatitis virus type 3 parallels disease susceptibility in mice,,PMC2186492,6270227,CC BY-NC-SA,"The in vitro induction of procoagulant activity (PCA) in murine peripheral blood mononuclear cells (PBM) by murine hepatitis virus type 3 (MHV-3) correlates with the disease susceptibility in three strains of mice. PBM from BALB/c mice, a strain in which MHV-3 infection results in fatal acute fulminant hepatitis, responds to the virus with a robust PCA response, whereas PBM from C3H/St mice, a strain which develops mild acute hepatitis followed by chronic hepatitis, only exhibit a modest PCA response. In contrast, PBM from A/J mice, a strain fully resistant to MHV-3, generate no increase in PCA above control levels. The induction phase of MHV-3 PCA is rapid, with an increase within 1-1.5 h, with maximum activity at 18h, and it precedes MHV-3 replication in either 17 CL1 cells, a fully permissive cell line, or in monocytes from these strains of mice. The PCA response of BALB/c PBM exceeds the response to any other known stimulus. No induction occurs upon direct stimulation of monocytes by MHV-3, but in the presence of lymphocyte collaboration, the PCA response is observed first at a lymphocyte:monocyte ratio of 2:1 and reaches a maximum as the lymphocyte:monocyte ratio approaches 4:1. This response appears to provide a functional marker for susceptibility to MHV-3 infection in inbred strains of mice and could be important in the pathogenesis of MHV-3-induced disease.",1981 Oct 1,,J Exp Med,,,True
2176706829fb93fa471a706137b138e8766b4f32,PMC,Graft-versus-host disease in cyclosporin A-treated rats after syngeneic and autologous bone marrow reconstitution,,PMC2187068,6345713,CC BY-NC-SA,"Lethally irradiated rats treated with cyclosporin A (CsA) for 20-40 d develop classic graft-versus-host disease (GVHD) when reconstituted with syngeneic or autologous bone marrow, upon discontinuation of CsA, whereas normal rats do not. Syngeneic GVHD may be transferred to irradiated but not normal syngeneic recipients. Normal spleen cells fail to prevent the development or adoptive transfer of syngeneic GVHD.",1983 Jul 1,,J Exp Med,,,True
bbaa88d5b0e10a260606dc92d0774816a3bb5861,PMC,Age-related factors in cyclosporine-induced syngeneic graft-versus-host disease: regulatory role of marrow-derived T lymphocytes,,PMC2188172,2358786,CC BY-NC-SA,"The present studies have evaluated the effect of age on the induction of syngeneic graft-versus-host disease (SGVHD) after syngeneic bone marrow transplantation (BMT) and cyclosporine (CsA) therapy. The results clearly document an inverse correlation of age with the incidence of SGVHD. Virtually a 100% incidence of SGVHD occurs in Lewis rats when syngeneic BMT and CsA therapy are started when the animals are 4 wk of age. Thereafter, there is a dramatic decline in the incidence of SGVHD with the increasing age of the animals. Although the age of the recipient was important, the most significant effect was the age of the marrow donor. Marrow from animals 6 mo of age was virtually incapable of eliciting SGVHD after BMT and CsA therapy. Furthermore, mixing the marrow from mature and immature animals resulted in a decreased incidence of SGVHD, implicating a regulatory effect present in the marrow from older rats. This regulatory effect was due to the presence of mature T cells in the marrow from animals 6 mo of age. Despite the fact that marrow from young animals possesses mature T lymphocytes, this regulatory activity was absent, suggesting that the host resistance mediated by T lymphocytes develops as the animal ages. These data further implicate the importance of a host resistance mechanism in preventing the induction of SGVHD with CsA, which appears to be mediated by the clonal inactivation of autoreactive cells.",1990 Jul 1,,J Exp Med,,,True
61f4cc62aa5a8b65d63664101a7e4af71a7c1df4,PMC,Double isotype production by a neoplastic B cell line. II. Allelically excluded production of mu and gamma 1 heavy chains without CH gene rearrangement,,PMC2188233,3088208,CC BY-NC-SA,"In our accompanying paper, we described a switch variant (BCL1.2.58) that expresses membrane and secreted forms of IgM and IgG1. Both IgM and IgG1 share the same idiotype and use the same VDJ rearrangement. Here, a detailed Southern blot analysis of the entire constant region of the Ig heavy chain (Ig CH) locus of parental (BCL1.B1) and variants (BCL1.B2) DNA showed no detectable rearrangement. Similar analysis of the JH-C mu region led to the conclusion that two heavy chain alleles present in the IgM/IgG1-producing variants carried the same VDJ rearrangement but differed in their 3' flanking regions. One chromosome 12 did not carry any Ig CH genes, whereas, the other chromosome 12 carried one copy of CH genes. In BCL1.B1, however, each of the chromosome 12 alleles carried a full copy of CH genes. Karyotypic analysis confirmed the presence of two translocated t(12;16) chromosomes in both BCL1.2.58 and BCL1.B1 cells, with a break 5' to the VH locus at the distal region (12F2) of chromosome 12, and at the proximal region below the centromere (16B3) of chromosome 16. We conclude that double production of IgM and IgG1 in BCL1.B2 is accomplished by transcription of the corresponding CH genes in germline configuration using a single VDJ on the same chromosome 12.",1986 Aug 1,,J Exp Med,,,True
b1870c85dae2f3bd004c29206c9a0281f4a9a249,PMC,Effect of olfactory bulb ablation on spread of a neurotropic coronavirus into the mouse brain,,PMC2188595,1698910,CC BY-NC-SA,"Previous results suggested that, after intranasal inoculation, mouse hepatitis virus (MHV), a neurotropic coronavirus, entered the central nervous system (CNS) via the olfactory and trigeminal nerves. To prove this hypothesis, the effect of interruption of the olfactory pathway on spread of the virus was studied using in situ hybridization. Unilateral surgical ablation of this pathway prevented spread of the virus via the olfactory tract on the side of the lesion. MHV RNA could be detected, however, at distal sites on the operated side, indicating that the virus spread via well-described circuits involving the anterior commissure from the control (intact) side of the brain. Viral transport via the trigeminal nerve was not affected by removal of the olfactory bulb, showing that the surgical procedure was specific for the olfactory pathway. These results prove conclusively that MHV gains entry to the CNS via a transneuronal route, and spreads to additional sites in the brain via known neuroanatomic pathways.",1990 Oct 1,,J Exp Med,,,True
ec0a48de352326aecc319e76ea1f47b989ffcd8f,PMC,Inducibility of Ia antigen on astrocytes by murine coronavirus JHM is rat strain dependent,,PMC2188644,3036995,CC BY-NC-SA,"Inducibility of Ia molecules on cultivated astrocytes by JHM virus correlates with demyelinating disease susceptibility of animals from which these astrocytes are derived. On the contrary, class I induction of both astrocytes and oligodendrocytes occurs as a consequence of normal cultivation procedures in both susceptible and resistant strains. Increased expression of class I antigens on rat astrocytes and oligodendrocytes is not related to JHM viral infection as it is in the mouse. These data indicate that strain differences in Ia inducibility, rather than inducibility of class I antigens, by JHM virus may explain higher levels of T cell-mediated damage to myelin during infection in susceptible rat strains compared with resistant strains.",1987 Jul 1,,J Exp Med,,,True
653ebe846e79113660523aeb3d87942c3890cd05,PMC,"Development of graft-vs.-host disease-like syndrome in cyclosporine- treated rats after syngeneic bone marrow transplantation. I. Development of cytotoxic T lymphocytes with apparent polyclonal anti-Ia specificity, including autoreactivity",,PMC2189060,2580038,CC BY-NC-SA,"Lethally irradiated rats reconstituted with syngeneic bone marrow and treated with cyclosporine (CsA) for 40 d develop a graft-vs.-host disease-like syndrome (GVHD) after CsA therapy. We attempted to assess the development of autoreactivity in these animals. Results revealed that a majority of the animals with syngeneic GVHD develop autocytotoxic T lymphocytes of the OX8 phenotype. In addition to reactivity with self, these cells were capable of lysing appropriate target cells from a variety of different rat strains. The target antigens appeared to be class II major histocompatibility antigens, because lysis could be effectively blocked by an anti-Ia monoclonal antibody. Cold target inhibition studies indicated that one effector cell was capable of lysing various target cells, and provided evidence against a polyclonal activation of multiple anti-Ia-reactive cells. These results suggested that the anti-class II autoreactive cell associated with syngeneic GVHD either recognizes a common class II determinant (""public"" epitope) shared by multiple strains of rats, or was polyspecific with respect to ""private"" class II determinants.",1985 Apr 1,,J Exp Med,,,True
6bc8969058239852857384c5a87a7e75f41193b6,PMC,Requirements for the induction and adoptive transfer of cyclosporine- induced syngeneic graft-versus-host disease,,PMC2189285,2647891,CC BY-NC-SA,"These studies further delineate the requirements for the establishment and transfer of SGVHD. We show that (a) two mechanisms distinguishable by radiation and drug sensitivities exist, (b) lethal irradiation correlates with a 100% incidence in the induction of SGVHD, whereas (c) both sublethal or lethal irradiation and cytoxan therapy are effective in ablating the host autoregulatory system in order to transfer autoreactivity, (d) unfractionated as well as nylon wool-nonadherent splenocytes effectively inhibit the transfer of autoimmunity, and (e) OX19 depletion of that population, however, destroys the autoregulatory effect present in normal splenocytes. To demonstrate complete inhibition of immune reactivity, twice the number of unfractionated splenocytes from normal animals was required for every splenocyte from autoimmune donors. Last, the infusion of effector splenocytes on 4, 7, and 14 d after transplantation correlates to a decrease from 100%, 70 to 0% incidence of SGVHD, thus emulating the incidence obtained in a pretransplant rat within 2 wk. These findings further clarify the immunobiological complexity of SGVHD and suggest that since autoregulatory cells already exist in normal animals that CsA-induced autoimmunity is a reflection of not an induced reactivity specific to one therapeutic reagent but the uncoupling of normal immunologic mechanisms essential in controlling autoimmunity.",1989 Mar 1,,J Exp Med,,,True
ff6d57f2aad99be129432058665b361dc18747e8,PMC,Macrophages genetically resistant to mouse hepatitis virus converted in vitro to susceptible macrophages,,PMC2190139,175127,CC BY-NC-SA,"Genetic resistance to mouse hepatitis, which resides largely in the macrophages of resistant C3H mice, may be altered by exposing the cells in vitro to fluid from allogeneic mixed lymphocytes. A 1,000-fold increase in susceptibility was produced in these genetically resistant cells by exposure to this fluid. This presumed lymphokine was effective without producing any change in host adaption of the virus.",1976 Mar 1,,J Exp Med,,,True
1425915f5f44c6e2bb0753cbe0531cbcbad46d13,PMC,Differential tumor necrosis factor alpha expression by astrocytes from experimental allergic encephalomyelitis-susceptible and -resistant rat strains,,PMC2190814,1901078,CC BY-NC-SA,"There is evidence that the cytokine tumor necrosis factor alpha (TNF- alpha) contributes to the pathogenesis of neurological autoimmune diseases such as multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). TNF-alpha exerts damaging effects on oligodendrocytes, the myelin-producing cell of the central nervous system (CNS), and myelin itself. We have recently demonstrated TNF- alpha expression from astrocytes induced by lipopolysaccharide (LPS), interferon gamma (IFN-gamma), and interleukin 1 beta (IL-1 beta). Astrocytes secrete TNF-alpha in response to LPS alone, and can be primed by IFN-gamma to enhance LPS-induced TNF-alpha production. IFN- gamma and IL-1 beta, cytokines known to be present in the CNS during neurological disease states, do not induce TNF-alpha production alone, but act synergistically to stimulate astrocyte TNF-alpha expression. Inbred Lewis and Brown-Norway (BN) rats differ in genetic susceptibility to EAE, which is controlled in part by major histocompatibility complex (MHC) genes. We examined TNF-alpha gene expression by astrocytes derived from BN rats (resistant to EAE) and Lewis rats (highly susceptible). Astrocytes from BN rats express TNF- alpha mRNA and protein in response to LPS alone, yet IFN-gamma does not significantly enhance LPS-induced TNF-alpha expression, nor do they express appreciable TNF-alpha in response to the combined stimuli of IFN-gamma/IL-1 beta. In contrast, astrocytes from Lewis rats express low levels of TNF-alpha mRNA and protein in response to LPS, and are extremely responsive to the priming effect of IFN-gamma for subsequent TNF-alpha gene expression. Also, Lewis astrocytes produce TNF-alpha in response to IFN-gamma/IL-1 beta. The differential TNF-alpha production by astrocytes from BN and Lewis strains is not due to the suppressive effect of prostaglandins, because the addition of indomethacin does not alter the differential pattern of TNF-alpha expression. Furthermore, Lewis and BN astrocytes produce another cytokine, IL-6, in response to LPS, IFN-gamma, and IL-1 beta in a comparable fashion. Peritoneal macrophages and neonatal microglia from Lewis and BN rats are responsive to both LPS and IFN-gamma priming signals for subsequent TNF- alpha production, suggesting that differential TNF-alpha expression by the astrocyte is cell type specific. Taken together, these results suggest that differential TNF-alpha gene expression in response to LPS and IFN-gamma is strain and cell specific, and reflects both transcriptional and post-transcriptional control mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)",1991 Apr 1,,J Exp Med,,,True
2a0861490e83f24375ca14187de9617594666850,PMC,Molecular characterization of two human autoantigens: unique cDNAs encoding 95- and 160-kD proteins of a putative family in the Golgi complex,,PMC2191081,8315394,CC BY-NC-SA,"Serum autoantibodies from a patient with autoantibodies directed against the Golgi complex were used to screen clones from a HepG2 lambda Zap cDNA library. Three related clones, designated SY2, SY10, and SY11, encoding two distinct polypeptides were purified for further analysis. Antibodies affinity purified by adsorption to the lambda Zap- cloned recombinant proteins and antibodies from NZW rabbits immunized with purified recombinant proteins reproduced Golgi staining and bound two different proteins, 95 and 160 kD, from whole cell extracts. The SY11 protein was provisionally named golgin-95 and the SY2/SY10 protein was named golgin-160. The deduced amino acid sequence of the cDNA clone of SY2 and SY11 represented 58.7- and 70-kD proteins of 568 and 620 amino acids. The in vitro translation products of SY2 and SY11 cDNAs migrated in SDS-PAGE at 65 and 95 kD, respectively. The in vitro translated proteins were immunoprecipitated by human anti-Golgi serum or immune rabbit serum, but not by normal human serum or preimmune rabbit serum. Features of the cDNA suggested that SY11 was a full- length clone encoding golgin-95 but SY2 and SY10 together encoded a partial sequence of golgin-160. Analysis of the SY11 recombinant protein identified a leucine zipper spanning positions 419-455, a glutamic acid-rich tract spanning positions 322-333, and a proline-rich tract spanning positions 67-73. A search of the SwissProt data bank indicated sequence similarity of SY11 to human restin, the heavy chain of kinesin, and the heavy chain of myosin. SY2 shared sequence similarity with the heavy chain of myosin, the USO1 transport protein from yeast, and the 150-kD cytoplasmic dynein-associated polypeptide. Sequence analysis demonstrated that golgin-95 and golgin-160 share 43% sequence similarity and, therefore, may be functionally related proteins.",1993 Jul 1,,J Exp Med,,,True
8c4233100da83790ea6544851b543977da15a4ca,PMC,Susceptibility to cytotoxic T lymphocyte-induced apoptosis is a function of the proliferative status of the target,,PMC2191380,8294885,CC BY-NC-SA,"Cytotoxic T lymphocytes (CTL) kill cells by perturbing the target's plasma membrane and by inducing the disintegration of the target cell's DNA into oligonucleosomal fragments, a process characteristic of apoptosis. We show that the DNA fragmentation event is distinct from the membrane lysis event and is dependent on the state of target cell activation or commitment into the mitotic cycle. Quiescent cells were refractory to DNA fragmentation, but not to membrane lysis. Log phase growth, transformation with c-myc, or infection of quiescent G0 targets with herpes simplex virus-1, which induces a competent state for DNA synthesis, all enhanced target cell susceptibility to CTL-induced DNA fragmentation without altering the membrane lysis. These results suggest that G0 cells are resistant to CTL-induced apoptosis, but that entry into G1 or a G1-like state by growth factors, cellular transformation, or DNA virus infection renders them competent to enter the apoptotic pathway(s).",1994 Feb 1,,J Exp Med,,,True
aa51356108ada576b1b3a23b26c006b4e8d6cd4a,PMC,Coronavirus induction of class I major histocompatibility complex expression in murine astrocytes is virus strain specific,,PMC2191627,8064222,CC BY-NC-SA,"Neurotropic strains of mouse hepatitis viruses (MHV) such as MHV-A59 (A59) and MHV-4 (JHMV) cause acute and chronic encephalomyelitis and demyelination in susceptible strains of mice and rats. They are widely used as models of human demyelinating diseases such as multiple sclerosis (MS), in which immune mechanisms are thought to participate in the development of lesions in the central nervous system (CNS). The effects of MHV infection on target cell functions in the CNS are not well understood, but A59 has been shown to induce the expression of MHC class I molecules in glial cells after in vivo and in vitro infection. Changes in class I expression in infected cells may contribute to the immunopathogenesis of MHV infection in the CNS. In this communication, a large panel of MHV strains was tested for their ability to stimulate class I expression in primary astrocytes in vitro. The data show that the more hepatotropic strains, such as MHV-A59, MHV-1, MHV-2, MHV-3, MHV-D, MHV-K, and MHV-NuU, were potent inducers of class I expression in astrocytes during acute infection, measured by radioimmunoassay. The Kb molecule was preferentially expressed over Db. By contrast, JHMV and several viral strains derived from it did not stimulate the expression of class I molecules. Assays of virus infectivity indicated that the class I-inducing activity did not correlate with the ability of the individual viral strain to replicate in astrocytes. However, exposure of the viruses or the supernatants from infected astrocytes to ultraviolet light abolished the class I-inducing activity, indicating that infectious virus is required for class I expression. These data also suggest that class I expression was induced directly by virus infection, and not by the secretion of a soluble substance into the medium by infected astrocytes. Finally, analyses of A59/JHMV recombinant viral strains suggest that class I-inducing activity resides in one of the A59 structural genes.",1994 Sep 1,,J Exp Med,,,True
daf06fe518af2567566bd71fca278c8bc5fecddf,PMC,Human Mig chemokine: biochemical and functional characterization,,PMC2192190,7595201,CC BY-NC-SA,"Mig is a chemokine of the CXC subfamily that was discovered by differential screening of a cDNA library prepared from lymphokine- activated macrophages. The mig gene is inducible in macrophages and in other cells in response to interferon (IFN)-gamma. We have transfected Chinese hamster ovary (CHO) cells with cDNA encoding human Mig and we have derived CHO cell lines from which we have purified recombinant human Mig (rHuMig). rHuMig induced the transient elevation of [Ca2+]i in human tumor-infiltrating T lymphocytes (TIL) and in cultured, activated human peripheral blood-derived lymphocytes. No responses were seen in human neutrophils, monocytes, or Epstein-Barr virus-transformed B lymphoblastoid cell lines. rHuMig was chemotactic for TIL by a modified Boyden chamber assay but rHuMig was not chemotactic for neutrophils or monocytes. The CHO cell lines, IFN-gamma-treated human peripheral-blood monocytes, and IFN-gamma-treated cells of the human monocytic cell line THP-1 all secreted multiple and identical HuMig species as revealed by SDS-PAGE. Using the CHO-derived rHuMig, we have shown that the species' heterogeneity is due to proteolytic cleavage at basic carboxy-terminal residues, and that the proteolysis occurs before and not after rHuMig secretion by the CHO cells. The major species of secreted rHuMig ranged from 78 to 103 amino acids in length, the latter corresponding to the full-length secreted protein predicted from the HuMig cDNA. Carboxy-terminal-truncated forms of rHuMig were of lower specific activity compared to full-length rHuMig in the calcium flux assay, and the truncated species did not block the activity of the full- length species. It is likely that HuMig plays a role in T cell trafficking and perhaps in other aspects of the physiology of activated T cells.",1995 Nov 1,,J Exp Med,,,True
b41e1c74739ae2195dc07a54fd9decaff5639b45,PMC,Mice Lacking Expression of Secondary Lymphoid Organ Chemokine Have Defects in Lymphocyte Homing and Dendritic Cell Localization,,PMC2192914,9927507,CC BY-NC-SA,"Secondary lymphoid organ chemokine (SLC) is expressed in high endothelial venules and in T cell zones of spleen and lymph nodes (LNs) and strongly attracts naive T cells. In mice homozygous for the paucity of lymph node T cell (plt) mutation, naive T cells fail to home to LNs or the lymphoid regions of spleen. Here we demonstrate that expression of SLC is undetectable in plt mice. In addition to the defect in T cell homing, we demonstrate that dendritic cells (DCs) fail to accumulate in spleen and LN T cell zones of plt mice. DC migration to LNs after contact sensitization is also substantially reduced. The physiologic significance of these abnormalities in plt mice is indicated by a markedly increased sensitivity to infection with murine hepatitis virus. The plt mutation maps to the SLC locus; however, the sequence of SLC introns and exons in plt mice is normal. These findings suggest that the abnormalities in plt mice are due to a genetic defect in the expression of SLC and that SLC mediates the entry of naive T cells and antigen-stimulated DCs into the T cell zones of secondary lymphoid organs.",1999 Feb 1,"['Gunn, Michael D.', 'Kyuwa, Shigeru', 'Tam, Carmen', 'Kakiuchi, Terutaka', 'Matsuzawa, Akio', 'Williams, Lewis T.', 'Nakano, Hideki']",J Exp Med,,,True
57b32baae9c8cfd1be336a341fe0df2a55ad57bb,PMC,In Situ Tolerance within the Central Nervous System as a Mechanism for Preventing Autoimmunity,,PMC2193284,10993917,CC BY-NC-SA,"Multiple sclerosis (MS) is believed to be an autoimmune disease in which autoreactive T cells infiltrate the central nervous system (CNS). Animal models of MS have shown that CNS-specific T cells are present in the peripheral T cell repertoire of healthy mice and cause autoimmune disease only when they are activated by immunization. T cell entry into the CNS is thought to require some form of peripheral activation because the blood–brain barrier prohibits trafficking of this tissue by naive cells. We report here that naive T cells can traffic to the CNS without prior activation. Comparable numbers of T cells are found in the CNS of both healthy recombinase activating gene (Rag)(−/)− T cell receptor (TCR) transgenic mice and nontransgenic mice even when the transgenic TCR is specific for a CNS antigen. Transgenic T cells isolated from the CNS that are specific for non-CNS antigens are phenotypically naive and proliferate robustly to antigenic stimulation in vitro. Strikingly, transgenic T cells isolated from the CNS that are specific for myelin basic protein (MBP) are also primarily phenotypically naive but are unresponsive to antigenic stimulation in vitro. Mononuclear cells from the CNS of MBP TCR transgenic but not nontransgenic mice can suppress the response of peripheral MBP-specific T cells in vitro. These results indicate that naive MBP-specific T cells can traffic to the CNS but do not trigger autoimmunity because they undergo tolerance induction in situ.",2000 Sep 18,"['Brabb, Thea', 'von Dassow, Peter', 'Ordonez, Nadia', 'Schnabel, Bryan', 'Duke, Blythe', 'Goverman, Joan']",J Exp Med,,,True
fb4f03ec469640093e45b1bf924456d1cf05c07b,PMC,Murine Cytomegalovirus Is Regulated by a Discrete Subset of Natural Killer Cells Reactive with Monoclonal Antibody to Ly49h,,PMC2193438,11435470,CC BY-NC-SA,"Antiviral roles of natural killer (NK) cell subsets were examined in C57BL/6 mice infected with murine cytomegalovirus (MCMV) and other viruses, including lymphocytic choriomeningitis virus (LCMV), vaccinia virus (VV), and mouse hepatitis virus (MHV). Each virus vigorously induced an NK cell infiltrate into the peritoneal cavity and liver, causing some redistributions of NK cell subsets defined by monoclonal antibody (mAb) directed against Ly49A, C/I, D, and G2. Striking results were seen with a mAb (1F8) reactive with the positively signaling molecule Ly49H, present in MCMV-resistant C57BL/6 mice. mAb 1F8 also stains Ly49 C and I, but exclusion of those reactivities with mAb 5E6, which recognizes Ly49 C and I, indicated that Ly49H(+) cells infiltrated the peritoneal cavity and liver and were particularly effective at synthesizing interferon γ. Depletion of 1F8(+) but not 5E6(+) cells in vivo by mAb injections enhanced MCMV titers by 20-1,000-fold in the spleen and approximately fivefold in the liver. Titers of LCMV or VV were not enhanced. These anti-MCMV effects were attributed to prototypical NK1.1(+)CD3(−) NK cells and not to NK1.1(+)CD3(+) “NK/T” cells. This is the first evidence that control of a virus infection in vivo is mediated by a distinct NK cell subset.",2001 Jul 2,"['Daniels, Keith A.', 'Devora, Gene', 'Lai, Wayne C.', ""O'Donnell, Carey L."", 'Bennett, Michael', 'Welsh, Raymond M.']",J Exp Med,,,True
46eecf9daff1ef854fd51a8e6963d58126d35a2b,PMC,Molecular Mimicry of Human Cytochrome P450 by Hepatitis C Virus at the Level of Cytotoxic T Cell Recognition,,PMC2195568,10432280,CC BY-NC-SA,"Hepatitis C virus (HCV) is thought to be involved in the pathogenesis of autoimmune hepatitis (AIH) type 2, which is defined by the presence of type I antiliver kidney microsome autoantibodies directed mainly against cytochrome P450 (CYP)2D6 and by autoreactive liver infiltrating T cells. Virus-specific CD8(+) cytotoxic T lymphocytes (CTLs) that recognize infected cells and contribute to viral clearance and tissue injury during HCV infection could be involved in the induction of AIH. To explore whether the antiviral cellular immunity may turn against self-antigens, we characterized the primary CTL response against an HLA-A*0201–restricted HCV-derived epitope, i.e., HCV core 178–187, which shows sequence homology with human CYP2A6 and CYP2A7 8–17. To determine the relevance of these homologies for the pathogenesis of HCV-associated AIH, we used synthetic peptides to induce primary CTL responses in peripheral blood mononuclear cells of healthy blood donors and patients with chronic HCV infection. We found that the naive CTL repertoire of both groups contains cross-reactive CTLs inducible by the HCV peptide recognizing both CYP2A6 and CYP2A7 peptides as well as endogenously processed CYP2A6 protein. Importantly, we failed to induce CTLs with the CYP-derived peptides that showed a lower capacity to form stable complexes with the HLA-A2 molecule. These findings demonstrate the potential of HCV to induce autoreactive CD8(+) CTLs by molecular mimicry, possibly contributing to virus-associated autoimmunity.",1999 Jul 19,"['Kammer, Andreas R.', 'van der Burg, Sjoerd H.', 'Grabscheid, Benno', 'Hunziker, Isabelle P.', 'Kwappenberg, Kitty M.C.', 'Reichen, Jürg', 'Melief, Cornelis J.M.', 'Cerny, Andreas']",J Exp Med,,,True
d8ece7a7ece002e0a2fcdb9be3f1a85194079c1e,PMC,Homologue Scanning Mutagenesis Reveals Cd66 Receptor Residues Required for Neisserial Opa Protein Binding,,PMC2195581,10430622,CC BY-NC-SA,"The immunoglobulin-like family of CD66 antigens, present on human neutrophils and epithelial cells, are used as receptors for adhesins expressed by the pathogenic Neisseriae. N. gonorrhoeae strain MS11 can express 11 isoforms of these adhesins, called opacity-related (Opa) proteins. Each MS11 Opa protein recognizes a distinct spectrum of CD66 receptors. CD66–Opa binding is mediated by the NH(2)-terminal domain of the receptor and occurs through protein–protein interactions. In this report, we have investigated the molecular basis for the binding between the CD66 and Opa protein families by mapping amino acids in CD66 receptors that determine Opa protein binding. We performed homologue scanning mutagenesis between CD66e, which binds multiple Opa variants, and CD66b, which binds none, and tested both loss-of-function by CD66e and gain-of-function by CD66b in solution assays and in assays involving full-length receptors expressed by epithelial cells. We found that three residues in the CD66e N-domain are required for maximal Opa protein receptor activity. Opa proteins that recognize the same spectrum of native CD66 molecules showed differential binding of receptors with submaximal activity, indicating that the binding characteristics of these Opa proteins are actually slightly different. These data provide a first step toward resolving the structural requirements for Opa–CD66 interaction.",1999 Aug 2,"['Bos, Martine P.', 'Hogan, Daniel', 'Belland, Robert J.']",J Exp Med,,,True
ba4c40b65eb342713e70c96a8d6336b22cca54fc,PMC,9-O-Acetylation of Sialomucins: A Novel Marker of Murine CD4 T Cells that Is Regulated during Maturation and Activation,,PMC2196344,9166429,CC BY-NC-SA,"Terminal sialic acids on cell surface glycoconjugates can carry 9-O-acetyl esters. For technical reasons, it has previously been difficult to determine their precise distribution on different cell types. Using a recombinant soluble form of the Influenza C virus hemagglutinin-esterase as a probe for 9-O-acetylated sialic acids, we demonstrate here their preferential expression on the CD4 T cell lineage in normal B10.A mouse lymphoid organs. Of total thymocytes, 8–10% carry 9-O-acetylation; the great majority of these are the more mature PNA(−), HSA(−), and TCR(hi) medullary cells. While low levels of 9-O-acetylation are seen on some CD4/CD8 double positive (DP) and CD8 single positive (SP) cells, high levels are present primarily on 80– 85% of CD4 SP cells. Correlation with CD4 and CD8 levels suggests that 9-O-acetylation appears as an early differentiation marker as cells mature from the DP to the CD4 SP phenotype. This high degree of 9-O-acetylation is also present on 90–95% of peripheral spleen and lymph node CD4 T cells. In contrast, only a small minority of CD8 T cells and B cells show such levels of 9-O-acetylation. Among mature peripheral CD4 T lymphocytes, the highly O-acetylated cells are Mel 14(hi), CD44(lo), and CD45R(exon B)(hi), features typical of naive cells. Digestions with trypsin and O-sialoglycoprotease (OSGPase) and ELISA studies of lipid extracts indicate that the 9-O-acetylated sialic acids on peripheral CD4 T cells are predominantly on O-linked mucintype glycoproteins and to a lesser degree, on sialylated glycolipids (gangliosides). In contrast, sialic acids on mucin type molecules of CD8 T cells are not O-acetylated; instead these molecules mask the recognition of O-acetylated gangliosides that seem to be present at similar levels as on CD4 cells. The 9-O-acetylated gangliosides on mouse T cells are not bound by CD60 antibodies, which recognize O-acetylated gangliosides in human T cells. Tethering 9-O-acetylated mucins with the Influenza C probe with or without secondary cross-linking did not cause activation of CD4 T cells. However, activation by other stimuli including TCR ligation is associated with a substantial decrease in surface 9-O-acetylation, primarily in the mucin glycoprotein component. Thus, 9-O-acetylation of sialic acids on cell surface mucins is a novel marker on CD4 T cells that appears on maturation and is modulated downwards upon activation.",1997 Jun 2,"['Krishna, Murli', 'Varki, Ajit']",J Exp Med,,,True
8cd6d7c2eeb732eeecb6b7618d02eafe82aa62a4,PMC,Viral Infection of Transgenic Mice Expressing a Viral Protein in Oligodendrocytes Leads to Chronic Central Nervous System Autoimmune Disease,,PMC2196376,8976191,CC BY-NC-SA,"One hypothesis for the etiology of central nervous system (CNS) autoimmune disease is that infection by a virus sharing antigenic epitopes with CNS antigens (molecular mimicry) elicits a virus-specific immune response that also recognizes self-epitopes. To address this hypothesis, transgenic mice were generated that express the nucleoprotein or glycoprotein of lymphocytic choriomeningitis virus (LCMV) as self in oligodendrocytes. Intraperitoneal infection with LCMV strain Armstrong led to infection of tissues in the periphery but not the CNS, and the virus was cleared within 7–14 d. After clearance, a chronic inflammation of the CNS resulted, accompanied by upregulation of CNS expression of MHC class I and II molecules. A second LCMV infection led to enhanced CNS pathology, characterized by loss of myelin and clinical motor dysfunction. Disease enhancement also occurred after a second infection with unrelated viruses that cross-activated LCMV-specific memory T cells. These findings indicate that chronic CNS autoimmune disease may be induced by infection with a virus sharing epitopes with a protein expressed in oligodendrocytes and this disease may be enhanced by a second infection with the same or an unrelated virus. These results may explain the association of several different viruses with some human autoimmune diseases.",1996 Dec 1,"['Evans, Claire F.', 'Horwitz, Marc S.', 'Hobbs, Monte V.', 'Oldstone, Michael B.A.']",J Exp Med,,,True
1e5d47af3cdfd8ce02f55653005d7c8b75017e91,PMC,trans-Golgi retention of a plasma membrane protein: mutations in the cytoplasmic domain of the asialoglycoprotein receptor subunit H1 result in trans-Golgi retention,,PMC2199941,7615632,CC BY-NC-SA,"Unlike the wild-type asialoglycoprotein receptor subunit H1 which is transported to the cell surface, endocytosed and recycled, a mutant lacking residues 4-33 of the 40-amino acid cytoplasmic domain was found to be retained intracellularly upon expression in different cell lines. The mutant protein accumulated in the trans-Golgi, as judged from the acquisition of trans-Golgi-specific modifications of the protein and from the immunofluorescence staining pattern. It was localized to juxtanuclear, tubular structures that were also stained by antibodies against galactosyltransferase and gamma-adaptin. The results of further mutagenesis in the cytoplasmic domain indicated that the size rather than the specific sequence of the cytoplasmic domain determines whether H1 is retained in the trans-Golgi or transported to the cell surface. Truncation to less than 17 residues resulted in retention, and extension of a truncated tail by an unrelated sequence restored surface transport. The transmembrane segment of H1 was not sufficient for retention of a reporter molecule and it could be replaced by an artificial apolar sequence without affecting Golgi localization. The cytoplasmic domain thus appears to inhibit interaction(s) of the exoplasmic portion of H1 with trans-Golgi component(s) for example by steric hindrance or by changing the positioning of the protein in the membrane. This mechanism may also be functional in other proteins.",1995 Jul 2,,J Cell Biol,,,True
649b681845a59b87d339917c75ef51c6c55b3a46,PMC,Envelope glycoprotein interactions in coronavirus assembly,,PMC2199982,7593163,CC BY-NC-SA,"Coronaviruses are assembled by budding into smooth membranes of the intermediate ER-to-Golgi compartment. We have studied the association of the viral membrane glycoproteins M and S in the formation of the virion envelope. Using coimmunoprecipitation analysis we demonstrated that the M and S proteins of mouse hepatitis virus (MHV) interact specifically forming heteromultimeric complexes in infected cells. These could be detected only when the detergents used for their solubilization from cells or virions were carefully chosen: a combination of nonionic (NP-40) and ionic (deoxycholic acid) detergents proved to be optimal. Pulse-chase experiments revealed that newly made M and S proteins engaged in complex formation with different kinetics. Whereas the M protein appeared in complexes immediately after its synthesis, newly synthesized S protein did so only after a lag phase of > 20 min. Newly made M was incorporated into virus particles faster than S, which suggests that it associates with preexisting S molecules. Using the vaccinia virus T7-driven coexpression of M and S we also demonstrate formation of M/S complexes in the absence of other coronaviral proteins. Pulse-chase labelings and coimmunoprecipitation analyses revealed that M and S associate in pre-Golgi membranes because the unglycosylated form of M appeared in M/S complexes rapidly. Since no association of M and S was detected when protein export from the ER was blocked by brefeldin A, stable complexes most likely arise in the ER-to-Golgi intermediate compartment. Sucrose velocity gradient analysis showed the M/S complexes to be heterogeneous and of higher order, suggesting that they are maintained by homo- and heterotypic interactions. M/S complexes colocalized with alpha-mannosidase II, a resident Golgi protein. They acquired Golgi-specific oligosaccharide modifications but were not detected at the cell surface. Thus, the S protein, which on itself was transported to the plasma membrane, was retained in the Golgi complex by its association with the M protein. Because coronaviruses bud at pre-Golgi membranes, this result implies that the envelope glycoprotein complexes do not determine the site of budding. Yet, the self-association of the MHV envelope glycoproteins into higher order complexes is indicative of its role in the sorting of the viral membrane proteins and in driving the formation of the viral lipoprotein coat in virus assembly.",1995 Oct 2,,J Cell Biol,,,True
e3f5b91907bbd807d31fa063a9d629e574b4dbde,PMC,"Localization and targeting of the Saccharomyces cerevisiae Kre2p/Mnt1p alpha 1,2-mannosyltransferase to a medial-Golgi compartment",,PMC2200012,7490293,CC BY-NC-SA,"The yeast Kre2p/Mnt1p alpha 1,2-mannosyltransferase is a type II membrane protein with a short cytoplasmic amino terminus, a membrane- spanning region, and a large catalytic luminal domain containing one N- glycosylation site. Anti-Kre2p/Mnt1p antibodies identify a 60-kD integral membrane protein that is progressively N-glycosylated in an MNN1-dependent manner. Kre2p/Mnt1p is localized in a Golgi compartment that overlaps with that containing the medial-Golgi mannosyltransferase Mnn1p, and distinct from that including the late Golgi protein Kex1p. To determine which regions of Kre2p/Mnt1p are required for Golgi localization, Kre2p/Mnt1p mutant proteins were assembled by substitution of Kre2p domains with equivalent sequences from the vacuolar proteins DPAP B and Pho8p. Chimeric proteins were tested for correct topology, in vitro and in vivo activity, and were localized intracellularly by indirect immunofluorescence. The results demonstrate that the NH2-terminal cytoplasmic domain is necessary for correct Kre2p Golgi localization whereas, the membrane-spanning and stem domains are dispensable. However, in a test of targeting sufficiency, the presence of the entire Kre2p cytoplasmic tail, plus the transmembrane domain and a 36-amino acid residue luminal stem region was required to localize a Pho8p reporter protein to the yeast Golgi.",1995 Nov 2,,J Cell Biol,,,True
fb776803a925865af38ca4de4f23e94668455a02,PMC,Sequential coupling between COPII and COPI vesicle coats in endoplasmic reticulum to Golgi transport,,PMC2200014,7490291,CC BY-NC-SA,"COPI and COPII are vesicle coat complexes whose assembly is regulated by the ARF1 and Sar1 GTPases, respectively. We show that COPI and COPII coat complexes are recruited separately and independently to ER (COPII), pre-Golgi (COPI, COPII), and Golgi (COPI) membranes of mammalian cells. To address their individual roles in ER to Golgi transport, we used stage specific in vitro transport assays to synchronize movement of cargo to and from pre-Golgi intermediates, and GDP- and GTP-restricted forms of Sar1 and ARF1 proteins to control coat recruitment. We find that COPII is solely responsible for export from the ER, is lost rapidly following vesicle budding and mediates a vesicular step required for the build-up of pre-Golgi intermediates composed of clusters of vesicles and small tubular elements. COPI is recruited onto pre-Golgi intermediates where it initiates segregation of the anterograde transported protein vesicular stomatitis virus glycoprotein (VSV-G) from the retrograde transported protein p58, a protein which actively recycles between the ER and pre-Golgi intermediates. We propose that sequential coupling between COPII and COPI coats is essential to coordinate and direct bi-directional vesicular traffic between the ER and pre-Golgi intermediates involved in transport of protein to the Golgi complex.",1995 Nov 2,,J Cell Biol,,,True
6220d2580a3a4a5c86ea58944be947b5d4c0bc0b,PMC,Sorting signals in the MHC class II invariant chain cytoplasmic tail and transmembrane region determine trafficking to an endocytic processing compartment,,PMC2200027,8034737,CC BY-NC-SA,"Targeting of MHC class II molecules to the endocytic compartment where they encounter processed antigen is determined by the invariant chain (Ii). By analysis of Ii-transferrin receptor (TR) chimera trafficking, we have identified sorting signals in the Ii cytoplasmic tail and transmembrane region that mediate this process. Two non-tyrosine-based sorting signals in the Ii cytoplasmic tail were identified that mediate localization to plasma membrane clathrin-coated pits and promote rapid endocytosis. Leu7 and Ile8 were required for the activity of the signal most distal to the cell membrane whereas Pro15 Met16 Leu17 were important for the membrane-proximal signal. The same or overlapping non- tyrosine-based sorting signals are essential for delivery of Ii-TR chimeras, either by an intracellular route or via the plasma membrane, to an endocytic compartment where they are rapidly degraded. The Ii transmembrane region is also required for efficient delivery to this endocytic processing compartment and contains a signal distinct from the Ii cytoplasmic tail. More than 80% of the Ii-TR chimera containing the Ii cytoplasmic tail and transmembrane region is delivered directly to the endocytic pathway by an intracellular route, implying that the Ii sorting signals are efficiently recognized by sorting machinery located in the trans-Golgi.",1994 Jul 2,,J Cell Biol,,,True
5ed43fc646fb368da6a9cf9d0029891a4b8248d1,PMC,An ion-transporting ATPase encodes multiple apical localization signals,,PMC2200096,8385670,CC BY-NC-SA,"Epithelial cells accumulate distinct populations of membrane proteins at their two plasmalemmal domains. We have examined the molecular signals which specify the differential subcellular distributions of two closely related ion pumps. The Na,K-ATPase is normally restricted to the basolateral membranes of numerous epithelial cell types, whereas the H,K-ATPase is a component of the apical surfaces of the parietal cells of the gastric epithelium. We have expressed full length and chimeric H,K-ATPase/Na,K-ATPase cDNAs in polarized renal proximal tubular epithelial cells (LLC-PK1). We find that both the alpha and beta subunits of the H,K-ATPase encode independent signals that specify apical localization. Furthermore, the H,K-ATPase beta-subunit possesses a sequence which mediates its participation in the endocytic pathway. The interrelationship between epithelial sorting and endocytosis signals suggested by these studies supports the redefinition of apical and basolateral as functional, rather than simply topographic domains.",1993 Apr 2,,J Cell Biol,,,True
defb6d472091880138cc95da0589cb3bccbd51b2,PMC,The rubella virus E2 and E1 spike glycoproteins are targeted to the Golgi complex,,PMC2200098,8468347,CC BY-NC-SA,"Rubella virus (RV) has been reported to bud from intracellular membranes in certain cell types. In this study the intracellular site of targeting of RV envelope E2 and E1 glycoproteins has been investigated in three different cell types (CHO, BHK-21 and Vero cells) transfected with a cDNA encoding the two glycoproteins. By indirect immunofluorescence, E2 and E1 were localized to the Golgi region of all three cell types, and their distribution was disrupted by treatment with BFA or nocodazole. Immunogold labeling demonstrated that E2 and E1 were localized to Golgi cisternae and indicated that the glycoproteins were distributed across the Golgi stack. Analysis of immunoprecipitates obtained from stably transfected CHO cells revealed that E2 and E1 become endo H resistant and undergo sialylation without being transported to the cell surface. Transport of RV glycoproteins to the Golgi complex was relatively slow (t1/2 = 60-90 min). Coprecipitation experiments indicated that E2 and E1 form a heterodimer in the RER. E1 was found to fold much more slowly than E2, suggesting that the delay in transport of the heterodimer to the Golgi may be due to the slow maturation of E1 in the ER. These results indicate that RV glycoproteins behave as integral membrane proteins of the Golgi complex and thus provide a useful model to study targeting and turnover of type I membrane proteins in this organelle.",1993 Apr 2,,J Cell Biol,,,True
0994b9aa851f17dc1c6af309973fe189118ab6c5,PMC,"Secretory Leukocyte Protease Inhibitor Binds to Annexin II, a Cofactor for Macrophage HIV-1 Infection",http://dx.doi.org/10.1084/jem.20041115,PMC2211913,15545357,CC BY-NC-SA,"The distribution of secretory leukocyte protease inhibitor (SLPI) at entry portals indicates its involvement in defending the host from pathogens, consistent with the ability of SLPI to inhibit human immunodeficiency virus (HIV)-1 infection by an unknown mechanism. We now demonstrate that SLPI binds to the membrane of human macrophages through the phospholipid-binding protein, annexin II. Based on the recent identification of human cell membrane phosphatidylserine (PS) in the outer coat of HIV-1, we define a novel role for annexin II, a PS-binding moiety, as a cellular cofactor supporting macrophage HIV-1 infection. Moreover, this HIV-1 PS interaction with annexin II can be disrupted by SLPI or other annexin II–specific inhibitors. The PS–annexin II connection may represent a new target to prevent HIV-1 infection.",2004 Nov 15,"['Ma, Ge', 'Greenwell-Wild, Teresa', 'Lei, Kejian', 'Jin, Wenwen', 'Swisher, Jennifer', 'Hardegen, Neil', 'Wild, Carl T.', 'Wahl, Sharon M.']",J Exp Med,,,True
c761570812ca07ce01397ebabc220556f51e786e,PMC,Private specificities of CD8 T cell responses control patterns of heterologous immunity,http://dx.doi.org/10.1084/jem.20041337,PMC2213046,15710651,CC BY-NC-SA,"CD8 T cell cross-reactivity between viruses can play roles in protective heterologous immunity and damaging immunopathology. This cross-reactivity is sometimes predictable, such as between lymphocytic choriomeningitis virus (LCMV) and Pichinde virus, where cross-reactive epitopes share six out of eight amino acids. Here, however, we demonstrate more subtle and less predictable cross-reactivity between LCMV and the unrelated vaccinia virus (VV). Epitope-specific T cell receptor usage differed between individual LCMV-infected C57BL/6 mice, even though the mice had similar epitope-specific T cell hierarchies. LCMV-immune mice challenged with VV showed variations, albeit in a distinct hierarchy, in proliferative expansions of and down-regulation of IL-7Rα by T cells specific to different LCMV epitopes. T cell responses to a VV-encoded epitope that is cross-reactive with LCMV fluctuated greatly in VV-infected LCMV-immune mice. Adoptive transfers of splenocytes from individual LCMV-immune donors resulted in nearly identical VV-induced responses in each of several recipients, but responses differed depending on the donor. This indicates that the specificities of T cell responses that are not shared between individuals may influence cross-reactivity with other antigens and play roles in heterologous immunity upon encounter with another pathogen. This variability in cross-reactive T cell expansion that is unique to the individual may underlie variation in the pathogenesis of infectious diseases.",2005 Feb 21,"['Kim, Sung-Kwon', 'Cornberg, Markus', 'Wang, Xiaoting Z.', 'Chen, Hong D.', 'Selin, Liisa K.', 'Welsh, Raymond M.']",J Exp Med,,,True
acec6ab753cc4f3bdc2dd1e9b63d3ae8e32a3bae,PMC,Multiple organ infection and the pathogenesis of SARS,http://dx.doi.org/10.1084/jem.20050828,PMC2213088,16043521,CC BY-NC-SA,"After >8,000 infections and >700 deaths worldwide, the pathogenesis of the new infectious disease, severe acute respiratory syndrome (SARS), remains poorly understood. We investigated 18 autopsies of patients who had suspected SARS; 8 cases were confirmed as SARS. We evaluated white blood cells from 22 confirmed SARS patients at various stages of the disease. T lymphocyte counts in 65 confirmed and 35 misdiagnosed SARS cases also were analyzed retrospectively. SARS viral particles and genomic sequence were detected in a large number of circulating lymphocytes, monocytes, and lymphoid tissues, as well as in the epithelial cells of the respiratory tract, the mucosa of the intestine, the epithelium of the renal distal tubules, the neurons of the brain, and macrophages in different organs. SARS virus seemed to be capable of infecting multiple cell types in several organs; immune cells and pulmonary epithelium were identified as the main sites of injury. A comprehensive theory of pathogenesis is proposed for SARS with immune and lung damage as key features.",2005 Aug 1,"['Gu, Jiang', 'Gong, Encong', 'Zhang, Bo', 'Zheng, Jie', 'Gao, Zifen', 'Zhong, Yanfeng', 'Zou, Wanzhong', 'Zhan, Jun', 'Wang, Shenglan', 'Xie, Zhigang', 'Zhuang, Hui', 'Wu, Bingquan', 'Zhong, Haohao', 'Shao, Hongquan', 'Fang, Weigang', 'Gao, Dongshia', 'Pei, Fei', 'Li, Xingwang', 'He, Zhongpin', 'Xu, Danzhen', 'Shi, Xeying', 'Anderson, Virginia M.', 'Leong, Anthony S.-Y.']",J Exp Med,,,True
59a6b0bbb0666fddb456723c185f04bb97858b08,PMC,T cell aging: naive but not young,http://dx.doi.org/10.1084/jem.20050341,PMC2213096,15781575,CC BY-NC-SA,"The immune system exhibits profound age-related changes, collectively termed immunosenescence. The most visible of these is the decline in protective immunity, which results from a complex interaction of primary immune defects and compensatory homeostatic mechanisms. The sum of these changes is a dysregulation of many processes that normally ensure optimal immune function. Recent advances suggest that old mice can produce fully functional new T cells, opening both intriguing inquiry avenues and raising critical questions to be pursued.",2005 Mar 21,"Nikolich-Žugich, Janko",J Exp Med,,,True
0cea2b0d9b7187e2c5a596ed433be46208186d32,PMC,IDBD: Infectious Disease Biomarker Database,http://dx.doi.org/10.1093/nar/gkm925,PMC2238845,17982173,CC BY-NC,"Biomarkers enable early diagnosis, guide molecularly targeted therapy and monitor the activity and therapeutic responses across a variety of diseases. Despite intensified interest and research, however, the overall rate of development of novel biomarkers has been falling. Moreover, no solution is yet available that efficiently retrieves and processes biomarker information pertaining to infectious diseases. Infectious Disease Biomarker Database (IDBD) is one of the first efforts to build an easily accessible and comprehensive literature-derived database covering known infectious disease biomarkers. IDBD is a community annotation database, utilizing collaborative Web 2.0 features, providing a convenient user interface to input and revise data online. It allows users to link infectious diseases or pathogens to protein, gene or carbohydrate biomarkers through the use of search tools. It supports various types of data searches and application tools to analyze sequence and structure features of potential and validated biomarkers. Currently, IDBD integrates 611 biomarkers for 66 infectious diseases and 70 pathogens. It is publicly accessible at http://biomarker.cdc.go.kr and http://biomarker.korea.ac.kr.",2008 Jan 3,"['Yang, In Seok', 'Ryu, Chunsun', 'Cho, Ki Joon', 'Kim, Jin Kwang', 'Ong, Swee Hoe', 'Mitchell, Wayne P.', 'Kim, Bong Su', 'Oh, Hee-Bok', 'Kim, Kyung Hyun']",Nucleic Acids Res,,,True
85c04886b69b27eeddd4a72c74e2e1727a80598f,PMC,CoVDB: a comprehensive database for comparative analysis of coronavirus genes and genomes,http://dx.doi.org/10.1093/nar/gkm754,PMC2238867,17913743,CC BY-NC,"The recent SARS epidemic has boosted interest in the discovery of novel human and animal coronaviruses. By July 2007, more than 3000 coronavirus sequence records, including 264 complete genomes, are available in GenBank. The number of coronavirus species with complete genomes available has increased from 9 in 2003 to 25 in 2007, of which six, including coronavirus HKU1, bat SARS coronavirus, group 1 bat coronavirus HKU2, groups 2c and 2d coronaviruses, were sequenced by our laboratory. To overcome the problems we encountered in the existing databases during comparative sequence analysis, we built a comprehensive database, CoVDB (http://covdb.microbiology.hku.hk), of annotated coronavirus genes and genomes. CoVDB provides a convenient platform for rapid and accurate batch sequence retrieval, the cornerstone and bottleneck for comparative gene or genome analysis. Sequences can be directly downloaded from the website in FASTA format. CoVDB also provides detailed annotation of all coronavirus sequences using a standardized nomenclature system, and overcomes the problems of duplicated and identical sequences in other databases. For complete genomes, a single representative sequence for each species is available for comparative analysis such as phylogenetic studies. With the annotated sequences in CoVDB, more specific blast search results can be generated for efficient downstream analysis.",2008 Jan 2,"['Huang, Yi', 'Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Yuen, Kwok-yung']",Nucleic Acids Res,,,True
c5f1c29433d6c5e4bed3a83ee1c94f003f597ea4,PMC,An emerging cyberinfrastructure for biodefense pathogen and pathogen–host data,http://dx.doi.org/10.1093/nar/gkm903,PMC2239001,17984082,CC BY-NC,"The NIAID-funded Biodefense Proteomics Resource Center (RC) provides storage, dissemination, visualization and analysis capabilities for the experimental data deposited by seven Proteomics Research Centers (PRCs). The data and its publication is to support researchers working to discover candidates for the next generation of vaccines, therapeutics and diagnostics against NIAID's Category A, B and C priority pathogens. The data includes transcriptional profiles, protein profiles, protein structural data and host–pathogen protein interactions, in the context of the pathogen life cycle in vivo and in vitro. The database has stored and supported host or pathogen data derived from Bacillus, Brucella, Cryptosporidium, Salmonella, SARS, Toxoplasma, Vibrio and Yersinia, human tissue libraries, and mouse macrophages. These publicly available data cover diverse data types such as mass spectrometry, yeast two-hybrid (Y2H), gene expression profiles, X-ray and NMR determined protein structures and protein expression clones. The growing database covers over 23 000 unique genes/proteins from different experiments and organisms. All of the genes/proteins are annotated and integrated across experiments using UniProt Knowledgebase (UniProtKB) accession numbers. The web-interface for the database enables searching, querying and downloading at the level of experiment, group and individual gene(s)/protein(s) via UniProtKB accession numbers or protein function keywords. The system is accessible at http://www.proteomicsresource.org/.",2008 Jan 4,"['Zhang, C.', 'Crasta, O.', 'Cammer, S.', 'Will, R.', 'Kenyon, R.', 'Sullivan, D.', 'Yu, Q.', 'Sun, W.', 'Jha, R.', 'Liu, D.', 'Xue, T.', 'Zhang, Y.', 'Moore, M.', 'McGarvey, P.', 'Huang, H.', 'Chen, Y.', 'Zhang, J.', 'Mazumder, R.', 'Wu, C.', 'Sobral, B.']",Nucleic Acids Res,,,True
ad7e256a901378cfdb314e11ab3504eda659df42,PMC,Comprehensive viral oligonucleotide probe design using conserved protein regions,http://dx.doi.org/10.1093/nar/gkm1106,PMC2248741,18079152,CC BY-NC,"Oligonucleotide microarrays have been applied to microbial surveillance and discovery where highly multiplexed assays are required to address a wide range of genetic targets. Although printing density continues to increase, the design of comprehensive microbial probe sets remains a daunting challenge, particularly in virology where rapid sequence evolution and database expansion confound static solutions. Here, we present a strategy for probe design based on protein sequences that is responsive to the unique problems posed in virus detection and discovery. The method uses the Protein Families database (Pfam) and motif finding algorithms to identify oligonucleotide probes in conserved amino acid regions and untranslated sequences. In silico testing using an experimentally derived thermodynamic model indicated near complete coverage of the viral sequence database.",2008 Jan 13,"['Jabado, Omar J.', 'Liu, Yang', 'Conlan, Sean', 'Quan, P. Lan', 'Hegyi, Hédi', 'Lussier, Yves', 'Briese, Thomas', 'Palacios, Gustavo', 'Lipkin, W. I.']",Nucleic Acids Res,,,True
c55e262b24b28cbd200cae613d6de88c35807deb,PMC,The presence of the TAR RNA structure alters the programmed -1 ribosomal frameshift efficiency of the human immunodeficiency virus type 1 (HIV-1) by modifying the rate of translation initiation,http://dx.doi.org/10.1093/nar/gkm906,PMC2248755,17984074,CC BY-NC,"HIV-1 uses a programmed -1 ribosomal frameshift to synthesize the precursor of its enzymes, Gag-Pol. The frameshift efficiency that is critical for the virus replication, is controlled by an interaction between the ribosome and a specific structure on the viral mRNA, the frameshift stimulatory signal. The rate of cap-dependent translation initiation is known to be altered by the TAR RNA structure, present at the 5′ and 3′ end of all HIV-1 mRNAs. Depending upon its concentration, TAR activates or inhibits the double-stranded RNA-dependent protein kinase (PKR). We investigated here whether changes in translation initiation caused by TAR affect HIV-1 frameshift efficiency. CD4+ T cells and 293T cells were transfected with a dual-luciferase construct where the firefly luciferase expression depends upon the HIV-1 frameshift. Translation initiation was altered by adding TAR in cis or trans of the reporter mRNA. We show that HIV-1 frameshift efficiency correlates negatively with changes in the rate of translation initiation caused by TAR and mediated by PKR. A model is presented where changes in the rate of initiation affect the probability of frameshifting by altering the distance between elongating ribosomes on the mRNA, which influences the frequency of encounter between these ribosomes and the frameshift stimulatory signal.",2008 Jan 5,"['Gendron, Karine', 'Charbonneau, Johanie', 'Dulude, Dominic', 'Heveker, Nikolaus', 'Ferbeyre, Gerardo', 'Brakier-Gingras, Léa']",Nucleic Acids Res,,,True
e656205a61b48b8617e2ceb45b63b9caf753d2e3,PMC,"Constitutive and basal secretion from the endocrine cell line, AtT-20",,PMC2288887,1847928,CC BY-NC-SA,"A variant of the ACTH-secreting pituitary cell line, AtT-20, has been isolated that does not make ACTH, sulfated proteins characteristic of the regulated secretory pathway, or dense-core secretory granules but retains constitutive secretion. Unlike wild type AtT-20 cells, the variant cannot store or release on stimulation, free glycosaminoglycan (GAG) chains. In addition, the variant cells cannot store trypsinogen or proinsulin, proteins that are targeted to dense core secretory granules in wild type cells. The regulated pathway could not be restored by transfecting with DNA encoding trypsinogen, a soluble regulated secretory protein targeted to secretory granules. A comparison of secretion from variant and wild type cells allows a distinction to be made between constitutive secretion and basal secretion, the spontaneous release of regulated proteins that occurs in the absence of stimulation.",1991 Mar 1,,J Cell Biol,,,True
f94c7a970b81de90b8594683b77db556e15ebd9f,PMC,"PtK1 cells contain a nondiffusible, dominant factor that makes the Golgi apparatus resistant to brefeldin A",,PMC2289003,1710224,CC BY-NC-SA,"Brefeldin A (BFA) was shown in earlier studies of numerous cell types to inhibit secretion, induce enzymes of the Golgi stacks to redistribute into the ER, and to cause the Golgi cisternae to disappear. Here, we demonstrate that the PtK1 line of rat kangaroo kidney cells is resistant to BFA. The drug did not disrupt the morphology of the Golgi complex in PtK1 cells, as judged by immunofluorescence using antibodies to 58- (58K) and 110-kD (beta-COP) Golgi proteins, and by fluorescence microscopy of live cells labeled with C6-NBD-ceramide. In addition, BFA did not inhibit protein secretion, not alter the kinetics or extent of glycosylation of the vesicular stomatitis virus (VSV) glycoprotein (G-protein) in VSV- infected PtK1 cells. To explore the mechanism of resistance to BFA, PtK1 cells were fused with BFA-sensitive CV-1 cells that had been infected with a recombinant SV-40 strain containing the gene for VSV G- protein and, at various times following fusion, the cultures were exposed to BFA. Shortly after cell fusion, heterokaryons contained one Golgi complex associated with each nucleus. Golgi membranes derived from CV-1 cells were sensitive to BFA, whereas those of PtK1 origin were BFA resistant. A few hours after fusion, most heterokaryons contained a single, large Golgi apparatus that was resistant to BFA and contained CV-1 galactosyltransferase. In unfused cells that had been perforated using nitrocellulose filters, retention of beta-COP on the Golgi was optimal in the presence of cytosol, ATP, and GTP. In perforated cell models of the BFA-sensitive MA104 line, BFA caused beta- COP to be released from the Golgi complex in the presence of nucleotides, and either MA104 or PtK1 cytosol. In contrast, when perforated PtK1 cells were incubated with BFA, nucleotides, and cytosol from either cell type, beta-COP remained bound to the Golgi complex. We conclude that PtK1 cells contain a nondiffusible factor, which is located on or very close to the Golgi complex, and confers a dominant resistance to BFA. It is possible that this factor is homologous to the target of BFA in cells that are sensitive to the drug.",1991 Jun 1,,J Cell Biol,,,True
2a0dccbe06cd6c48fdafcae920f220b3fdccab41,PMC,"Milieu-induced, selective aggregation of regulated secretory proteins in the trans-Golgi network",,PMC2289203,1757460,CC BY-NC-SA,"Regulated secretory proteins are thought to be sorted in the trans- Golgi network (TGN) via selective aggregation. The factors responsible for this aggregation are unknown. We show here that two widespread regulated secretory proteins, chromogranin B and secretogranin II (granins), remain in an aggregated state when TGN vesicles from neuroendocrine cells (PC12) are permeabilized at pH 6.4 in 1-10 mM calcium, conditions believed to exist in this compartment. Permeabilization of immature secretory granules under these conditions allowed the recovery of electron dense cores. The granin aggregates in the TGN largely excluded glycosaminoglycan chains which served as constitutively secreted bulk flow markers. The low pH, high calcium milieu was sufficient to induce granin aggregation in the RER. In the TGN of pituitary GH4C1 cells, the proportion of granins conserved as aggregates was higher upon hormonal treatment known to increase secretory granule formation. Our data suggest that a decrease in pH and an increase in calcium are sufficient to trigger the selective aggregation of the granins in the TGN, segregating them from constitutive secretory proteins.",1991 Dec 2,,J Cell Biol,,,True
eb136cf532bef626a3f5d4d32fef88e7b43ef3fb,PMC,"Isolation, characterization, and expression of cDNAs encoding murine alpha-mannosidase II, a Golgi enzyme that controls conversion of high mannose to complex N-glycans",,PMC2289207,1757461,CC BY-NC-SA,"Golgi alpha-mannosidase II (GlcNAc transferase I-dependent alpha 1,3[alpha 1,6] mannosidase, EC 3.2.1.114) catalyzes the final hydrolytic step in the N-glycan maturation pathway acting as the committed step in the conversion of high mannose to complex type structures. We have isolated overlapping clones from a murine cDNA library encoding the full length alpha-mannosidase II open reading frame and most of the 5' and 3' untranslated region. The coding sequence predicts a type II transmembrane protein with a short cytoplasmic tail (five amino acids), a single transmembrane domain (21 amino acids), and a large COOH-terminal catalytic domain (1,124 amino acids). This domain organization which is shared with the Golgi glycosyl-transferases suggests that the common structural motifs may have a functional role in Golgi enzyme function or localization. Three sets of polyadenylated clones were isolated extending 3' beyond the open reading frame by as much as 2,543 bp. Northern blots suggest that these polyadenylated clones totaling 6.1 kb in length correspond to minor message species smaller than the full length message. The largest and predominant message on Northern blots (7.5 kb) presumably extends another approximately 1.4-kb downstream beyond the longest of the isolated clones. Transient expression of the alpha-mannosidase II cDNA in COS cells resulted in 8-12-fold overexpression of enzyme activity, and the appearance of cross-reactive material in a perinuclear membrane array consistent with a Golgi localization. A region within the catalytic domain of the alpha-mannosidase II open reading frame bears a strong similarity to a corresponding sequence in the rat liver endoplasmic reticulum alpha-mannosidase and the vacuolar alpha- mannosidase of Saccharomyces cerevisiae. Partial human alpha- mannosidase II cDNA clones were also isolated and the gene was localized to human chromosome 5.",1991 Dec 2,,J Cell Biol,,,True
5b355d4f9adcfca08906339ef42a4990b1e9c8b0,PMC,Uncoupling of chondroitin sulfate glycosaminoglycan synthesis by brefeldin A,,PMC2289244,1955486,CC BY-NC-SA,"Brefeldin A has dramatic, well-documented, effects on the structural and functional organization of the Golgi complex. We have examined the effects of brefeldin A (BFA) on the Golgi-localized synthesis and addition of chondroitin sulfate glycosaminoglycan carbohydrate side chains. BFA caused a dose-dependent inhibition of chondroitin sulfate glycosaminoglycan elongation and sulfation onto the core proteins of the melanoma-associated proteoglycan and the major histocompatibility complex class II-associated invariant chain. In the presence of BFA, the melanoma proteoglycan core protein was retained in the ER but still acquired complex, sialylated, N-linked oligosaccharides, as measured by digestion with endoglycosidase H and neuraminidase. The initiation of glycosaminoglycan synthesis was not affected by BFA, as shown by the incorporation of [6-3H]galactose into a protein-carbohydrate linkage region that was sensitive to beta-elimination. The ability of cells to use an exogenous acceptor, p-nitrophenyl-beta-D-xyloside, to elongate and sulfate core protein-free glycosaminoglycans, was completely inhibited by BFA. The effects of BFA were completely reversible in the absence of new protein synthesis. These experiments indicate that BFA effectively uncouples chondroitin sulfate glycosaminoglycan synthesis by segregating initiation reactions from elongation and sulfation events. Our findings support the proposal that glycosaminoglycan elongation and sulfation reactions are associated with the trans-Golgi network, a BFA-resistant, Golgi subcompartment.",1991 Dec 1,,J Cell Biol,,,True
ff83907653a4c4500e8c509ca28169e924742b40,PMC,Identification of a subdomain of CENP-B that is necessary and sufficient for localization to the human centromere,,PMC2289363,1740467,CC BY-NC-SA,"We have combined in vivo and in vitro approaches to investigate the function of CENP-B, a major protein of human centromeric heterochromatin. Expression of epitope-tagged deletion derivatives of CENP-B in HeLa cells revealed that a single domain less than 158 residues from the amino terminus of the protein is sufficient to localize CENP-B to centromeres. Centromere localization was abolished if as few as 28 amino acids were removed from the amino terminus of CENP-B. The centromere localization signal of CENP-B can function in an autonomous fashion, relocating a fused bacterial enzyme to centromeres. The centromere localization domain of CENP-B specifically binds in vitro to a subset of alpha-satellite DNA monomers. These results suggest that the primary mechanism for localization of CENP-B to centromeres involves the recognition of a DNA sequence found at centromeres. Analysis of the distribution of this sequence in alpha- satellite DNA suggests that CENP-B binding may have profound effects on chromatin structure at centromeres.",1992 Mar 1,,J Cell Biol,,,True
885674f9e88e504ac2fed625ec9c64fdc3ad71f0,PMC,"The 17-residue transmembrane domain of beta-galactoside alpha 2,6- sialyltransferase is sufficient for Golgi retention",,PMC2289426,1560026,CC BY-NC-SA,"beta-Galactoside alpha 2,6-sialyltransferase (ST) is a type II integral membrane protein of the Golgi apparatus involved in the sialylation of N-linked glycans. A series of experiments has shown that the 17-residue transmembrane domain of ST is sufficient to confer localization to the Golgi apparatus when transferred to the corresponding region of a cell surface type II integral membrane protein. Lectin affinity chromatography of chimeric proteins bearing this 17-residue sequence suggests that these chimeric proteins are localized in the trans-Golgi cisternae and/or trans-Golgi network. Further experiments suggest that this 17-residue sequence functions as a retention signal for the Golgi apparatus.",1992 Apr 2,,J Cell Biol,,,True
23b89b2ee6a5870dd94c479b892cda6a54c8ab6f,PMC,Intermediates in the constitutive and regulated secretory pathways released in vitro from semi-intact cells,,PMC2289447,1572894,CC BY-NC-SA,"Regulated secretory cells have two pathways that transport secreted proteins from the Golgi complex to the cell surface. To identify carrier vesicles involved in regulated and constitutive secretion, PC12 pheochromocytoma cells were labeled with [35S]sulfate to identify markers for the two secretory pathways, then mechanically permeabilized and incubated in vitro. Small constitutive secretory vesicles, containing mostly sulfated proteoglycans, accumulated during an in vitro incubation with ATP. In the presence of GTP gamma S, the constitutive vesicles became significantly more dense, suggesting that a coated intermediate was stabilized. Larger immature regulated secretory granules, enriched in sulfated secretogranin II, also escaped from the permeabilized cells in vitro. During granule maturation, their density increased and the amount of cofractionating proteoglycans diminished. The data suggest that sorting continues during secretory granule maturation.",1992 May 1,,J Cell Biol,,,True
3041dc5ba951755241ae7e75ade271188033d4de,PMC,O-glycosylation of intact and truncated ribophorins in brefeldin A- treated cells: newly synthesized intact ribophorins are only transiently accessible to the relocated glycosyltransferases,,PMC2289488,1577870,CC BY-NC-SA,"Ribophorins I and II are type I transmembrane glycoproteins of the ER that are segregated to the rough domains of this organelle. Both ribophorins appear to be part of the translocation apparatus for nascent polypeptides that is associated with membrane-bound ribosomes and participate in the formation of a proteinaceous network within the ER membrane that also includes other components of the translocation apparatus. The ribophorins are both highly stable proteins that lack O- linked sugars but each contains one high mannose N-linked oligosaccharide that remains endo H sensitive throughout their lifetimes. We have previously shown (Tsao, Y. S., N. E. Ivessa, M. Adesnik, D. D. Sabatini, and G. Kreibich. 1992. J. Cell Biol. 116:57- 67) that a COOH-terminally truncated variant of ribophorin I that contains only the first 332 amino acids of the luminal domain (RI332), when synthesized in permanent transformants of HeLa cells, undergoes a rapid degradation with biphasic kinetics in the ER itself and in a second, as yet unidentified nonlysosomal pre-Golgi compartment. We now show that in cells treated with brefeldin A (BFA) RI332 molecules undergo rapid O-glycosylation in a multistep process that involves the sequential addition of N-acetylgalactosamine, galactose, and terminal sialic acid residues. Addition of O-linked sugars affected all newly synthesized RI332 molecules and was completed soon after synthesis with a half time of about 10 min. In the same cells, intact ribophorins I and II also underwent O-linked glycosylation in the presence of BFA, but these molecules were modified only during a short time period immediately after their synthesis was completed, and the modification affected only a fraction of the newly synthesized polypeptides. More important, these molecules synthesized before the addition of BFA were not modified by O-glycosylation. The same is true for ribophorin I when overexpressed in HeLa cells although it is significantly less stable than the native polypeptide in control cells. We, therefore, conclude that soon after their synthesis, ribophorins lose their susceptibility to the relocated Golgi enzymes that effect the O-glycosylation, most likely as a consequence of a conformational change in the ribophorins that occurs during their maturation, although it cannot be excluded that rapid integration of these molecules into a supramolecular complex in the ER membrane leads to their inaccessibility to these enzymes.",1992 Jun 1,,J Cell Biol,,,True
45ab08a84c5a80e9ba6a6d21eb814d0ab04a473c,PMC,"The rubella virus E1 glycoprotein is arrested in a novel post-ER, pre- Golgi compartment",,PMC2289574,1500424,CC BY-NC-SA,"Evidence is accumulating that a distinct compartment(s) exists in the secretory pathway interposed between the rough ER (RER) and the Golgi stack. In this study we have defined a novel post-RER, pre-Golgi compartment where unassembled subunits of rubella virus (RV) E1 glycoprotein accumulate. When RV E1 is expressed in CHO cells in the absence of E2 glycoprotein, transport of E1 to the Golgi complex is arrested. The compartment in which E1 accumulates consists of a tubular network of smooth membranes which is in continuity with the RER but has distinctive properties from either the RER, Golgi, or previously characterized intermediate compartments. It lacks RER and Golgi membrane proteins and is not disrupted by agents which disrupt either the RER (thapsigargin, ionomycin) or Golgi (nocodazole and brefeldin A). However, luminal ER proteins bearing the KDEL signal have access to this compartment. Kinetically the site of E1 arrest lies distal to or at the site where palmitylation occurs and proximal to the low temperature 15 degrees C block. Taken together the findings suggest that the site of E1 arrest corresponds to, or is located close to the exit site from the ER. This compartment could be identified morphologically because it is highly amplified in cells overexpressing unassembled E1 subunits, but it may have its counterpart among the transitional elements of non-transfected cells. We conclude that the site of E1 arrest may represent a new compartment or a differentiated proximal moiety of the intermediate compartment.",1992 Aug 2,,J Cell Biol,,,True
9b635859a59cb70b756b0768ec74405e226b5568,PMC,"Hepatitis B surface antigen assembles in a post-ER, pre-Golgi compartment",,PMC2289601,1522109,CC BY-NC-SA,"Expression of hepatitis B surface antigen (HBsAg), the major envelope protein of the virus, in the absence of other viral proteins leads to its secretion as oligomers in the form of disk-like or tubular lipoprotein particles. The observation that these lipoprotein particles are heavily disulphide crosslinked is paradoxical since HBsAg assembly is classically believed to occur in the ER, and hence in the presence of high levels of protein disulphide isomerase (PDI) which should resolve these higher intermolecular crosslinks. Indeed, incubation of mature, highly disulphide crosslinked HBsAg with recombinant PDI causes the disassembly of HBsAg to dimers. We have used antibodies against resident ER proteins in double immunofluorescence studies to study the stages of the conversion of the HBsAg from individual protein subunits to the secreted, crosslinked, oligomer. We show that HBsAg is rapidly sorted to a post-ER, pre-Golgi compartment which excludes PDI and other major soluble resident ER proteins although it overlaps with the distribution of rab2, an established marker of an intermediate compartment. Kinetic studies showed that disulphide-linked HBsAg dimers began to form during a short (2 min) pulse, increased in concentration to peak at 60 min, and then decreased as the dimers were crosslinked to form higher oligomers. These higher oligomers are the latest identifiable intracellular form of HBsAg before its secretion (t 1/2 = 2 h). Brefeldin A treatment does not alter the localization of HBsAg in this PDI excluding compartment, however, it blocks the formation of new oligomers causing the accumulation of dimeric HBsAg. Hence this oligomerization must occur in a pre-Golgi compartment. These data support a model in which rapid dimer formation, catalyzed by PDI, occurs in the ER, and is followed by transport of dimers to a pre-Golgi compartment where the absence of PDI and a different lumenal environment allow the assembly process to be completed.",1992 Sep 2,,J Cell Biol,,,True
8894efb9895e24c82697cf864b69e9a2eb0751c2,PMC,Membrane protein sorting in the yeast secretory pathway: evidence that the vacuole may be the default compartment,,PMC2289628,1527174,CC BY-NC-SA,"The targeting signals of two yeast integral membrane dipeptidyl aminopeptidases (DPAPs), DPAP B and DPAP A, which reside in the vacuole and the Golgi apparatus, respectively, were analyzed. No single domain of DPAP B is required for delivery to the vacuolar membrane, because removal or replacement of either the cytoplasmic, transmembrane, or lumenal domain did not affect the protein's transport to the vacuole. DPAP A was localized by indirect immunofluorescence to non-vacuolar, punctate structures characteristic of the yeast Golgi apparatus. The 118-amino acid cytoplasmic domain of DPAP A is sufficient for retention of the protein in these structures, since replacement of the cytoplasmic domain of DPAP B with that of DPAP A resulted in an immunolocalization pattern indistinguishable from that of wild type DPAP A. Overproduction of DPAP A resulted in its mislocalization to the vacuole, because cells expressing high levels of DPAP A exhibited vacuolar as well as Golgi staining. Deletion of 22 residues of the DPAP A cytoplasmic domain resulted in mislocalization of the mutant protein to the vacuole. Thus, the cytoplasmic domain of DPAP A is both necessary and sufficient for Golgi retention, and removal of the retention signal, or saturation of the retention apparatus by overproducing DPAP A, resulted in transport to the vacuole. Like wild type DPAP B, the delivery of mutant membrane proteins to the vacuole was unaffected in the secretory vesicle-blocked sec1 mutant; thus, transport to the vacuole was not via the plasma membrane followed by endocytosis. These data are consistent with a model in which membrane proteins are delivered to the vacuole along a default pathway.",1992 Oct 1,,J Cell Biol,,,True
8ba51fdaf2a9dc9a0b4defc7c07d360e0f9a3984,PMC,Yeast Kex1p is a Golgi-associated membrane protein: deletions in a cytoplasmic targeting domain result in mislocalization to the vacuolar membrane,,PMC2289743,1469044,CC BY-NC-SA,"We have investigated the localization of Kex1p, a type I transmembrane carboxypeptidase involved in precursor processing within the yeast secretory pathway. Indirect immunofluorescence demonstrated the presence of Kex1p in a punctate organelle resembling the yeast Golgi apparatus as identified by Kex2p and Sec7p (Franzusoff, A., K. Redding, J. Crosby, R. S. Fuller, and R. Schekman. 1991. J. Cell Biol. 112:27- 37). Glycosylation studies of Kex1p were consistent with a Golgi location, as Kex1p was progressively N-glycosylated in an MNN1- dependent manner. To address the basis of Kex1p targeting to the Golgi apparatus, we examined the cellular location of a series of carboxy- terminal truncations of the protein. The results indicate that a cytoplasmically exposed carboxy-terminal domain is required for retention of this membrane protein within the Golgi apparatus. Deletions of the retention region or overproduction of wild-type Kex1p led to mislocalization of Kex1p to the vacuolar membrane. This unexpected finding is discussed in terms of models involving either the vacuole as a default destination for membrane proteins, or by endocytosis to the vacuole following their default localization to the plasma membrane.",1992 Dec 2,,J Cell Biol,,,True
b06f31e9139111afe43967edf19c19335b9e79a4,PMC,The single transmembrane segment of gp210 is sufficient for sorting to the pore membrane domain of the nuclear envelope,,PMC2289754,1281815,CC BY-NC-SA,"The glycoprotein gp210 is located in the ""pore membrane,"" a specialized domain of the nuclear envelope to which the nuclear pore complex (NPC) is anchored. gp210 contains a large cisternal domain, a single transmembrane segment (TM), and a COOH-terminal, 58-amino acid residue cytoplasmic tail (CT) (Wozniak, R. W., E. Bartnik, and G. Blobel. 1989. J. Cell Biol. 108:2083-2092; Greber, U. F., A. Senior, and L. Gerace. 1990. EMBO (Eur. Mol. Biol. Organ.) J. 9:1495-1502). To locate determinants for sorting of gp210 to the pore membrane, we constructed various cDNAs coding for wild-type, mutant, and chimeric gp210, and monitored localization of the expressed protein in 3T3 cells by immunofluorescence microscopy using appropriate antibodies. The large cisternal domain of gp210 (95% of its mass) did not reveal any sorting determinants. Surprisingly, the TM of gp210 is sufficient for sorting to the pore membrane. The CT also contains a sorting determinant, but it is weaker than that of the TM. We propose specific lateral association of the transmembrane helices of two proteins to yield either a gp210 homodimer or a heterodimer of gp210 and another protein. The cytoplasmically oriented tails of these dimers may bind cooperatively to the adjacent NPCs. In addition, we demonstrate that gp210 co-localizes with cytoplasmically dispersed nucleoporins, suggesting a cytoplasmic association of these components.",1992 Dec 2,,J Cell Biol,,,True
5777ec2785cb535789796e239cc3627e92e24b83,PMC,A Golgi retention signal in a membrane-spanning domain of coronavirus E1 protein,,PMC2289920,1655802,CC BY-NC-SA,"The E1 glycoprotein from an avian coronavirus is a model protein for studying retention in the Golgi complex. In animal cells expressing the protein from cDNA, the E1 protein is targeted to cis Golgi cisternae (Machamer, C. E., S. A. Mentone, J. K. Rose, and M. G. Farquhar. 1990. Proc. Natl. Acad. Sci. USA. 87:6944-6948). We show that the first of the three membrane-spanning domains of the E1 protein can retain two different plasma membrane proteins in the Golgi region of transfected cells. Both the vesicular stomatitis virus G protein and the alpha- subunit of human chorionic gonadotropin (anchored to the membrane by fusion with the G protein membrane-spanning domain and cytoplasmic tail) were retained in the Golgi region of transfected cells when their single membrane-spanning domains were replaced with the first membrane- spanning domain from E1. Single amino acid substitutions in this sequence released retention of the chimeric G protein, as well as a mutant E1 protein which lacks the second and third membrane-spanning domains. The important feature of the retention sequence appears to be the uncharged polar residues which line one face of a predicted alpha helix. This is the first retention signal to be defined for a resident Golgi protein. The fact that it is present in a membrane-spanning domain suggests a novel mechanism of retention in which the membrane composition of the Golgi complex plays an instrumental role in retaining its resident proteins.",1991 Oct 1,,J Cell Biol,,,True
006be99e337c84b8758591a54f0362353b24dfde,PMC,Regulated export of a secretory protein from the ER of the hepatocyte: a specific binding site retaining C-reactive protein within the ER is downregulated during the acute phase response,,PMC2290050,1378445,CC BY-NC-SA,"The half-time for secretion of the plasma protein C-reactive protein (CRP) by the hepatocyte decreases markedly in association with its increased synthesis during the acute phase response to tissue injury (Macintyre, S., D. Samols, and I. Kushner. 1985. J. Biol. Chem. 260:4169-4173). In studies in which subcellular fractions were prepared from cells incubated under pulse-chase conditions, CRP was found to be preferentially retained within the ER of normal hepatocytes, but secreted relatively efficiently in cells prepared from rabbits undergoing the acute phase response. On the basis of the detergent- dependency of specific binding of radiolabeled CRP, as well as EM visualization of biotinylated CRP identified with peroxidase-conjugated streptavidin, CRP was found to bind to the lumenal surface of permeabilized rough microsomes, while no binding was detected in Golgi fractions. As judged by both kinetic and equilibrium binding studies, rough microsomes from control rabbits were found to have two classes of specific binding sites for CRP; a high affinity site (Kd = 1 nM, Bmax = 1 pmol CRP/mg microsomal protein) as well as a much lower affinity (Kd = 140 nM) site. In contrast, only the lower affinity class was detected in microsomes isolated from rabbits undergoing the acute phase response. On nitrocellulose blots probed with radiolabeled CRP a 60-kD protein, distinct from BiP, was detected in extracts of rough microsomes isolated from control rabbits, but not in Golgi fractions or rough microsomes from stimulated animals. These findings correlate with previous observations of changes in secretion kinetics of CRP and are consistent with the hypothesis that the intracellular sorting of CRP could be rerouted by downregulation of a specific ER binding site during the acute phase response.",1992 Jul 2,,J Cell Biol,,,True
3c6ed103b79757989428ac0f837b7a69f0d62b86,PMC,Microsomal aldehyde dehydrogenase is localized to the endoplasmic reticulum via its carboxyl-terminal 35 amino acids,,PMC2290952,8089174,CC BY-NC-SA,"Rat microsomal aldehyde dehydrogenase (msALDH) has no amino-terminal signal sequence, but instead it has a characteristic hydrophobic domain at the carboxyl terminus (Miyauchi, K., R. Masaki, S. Taketani, A. Yamamoto, A. Akayama, and Y. Tashiro. 1991. J. Biol. Chem. 266:19536- 19542). This membrane-bound enzyme is a useful model protein for studying posttranslational localization to its final destination. When expressed from cDNA in COS-1 cells, wild-type msALDH is localized exclusively in the well-developed ER. The removal of the hydrophobic domain results in the cytosolic localization of truncated proteins, thus suggesting that the portion is responsible for membrane anchoring. The last 35 amino acids of msALDH, including the hydrophobic domain, are sufficient for targeting of E. coli beta-galactosidase to the ER membrane. Further studies using chloramphenicol acetyltransferase fusion proteins suggest that two hydrophilic sequences on either side of the hydrophobic domain play an important role in ER targeting.",1994 Sep 2,,J Cell Biol,,,True
151b29e4b482ad11ee11e83cec4f3faebb8124c5,PMC,Oligomerized transferrin receptors are selectively retained by a lumenal sorting signal in a long-lived endocytic recycling compartment,,PMC2291173,7790351,CC BY-NC-SA,"Cross-linking of surface receptors results in altered receptor trafficking in the endocytic system. To better understand the cellular and molecular mechanisms by which receptor cross-linking affects the intracellular trafficking of both ligand and receptor, we studied the intracellular trafficking of the transferrin receptor (TfR) bound to multivalent-transferrin (Tf10) which was prepared by chemical cross- linking of transferrin (Tf). Tf10 was internalized about two times slower than Tf and was retained four times longer than Tf, without being degraded in CHO cells. The intracellular localization of Tf10 was investigated using fluorescence and electron microscopy. Tf10 was not delivered to the lysosomal pathway followed by low density lipoprotein but remained accessible to Tf in the pericentriolar endocytic recycling compartment for at least 60 min. The retained Tf10 was TfR-associated as demonstrated by a reduction in surface TfR number when cells were incubated with Tf10. The presence of Tf10 within the recycling compartment did not affect trafficking of subsequently endocytosed Tf. Retention of Tf10 within the recycling compartment did not require the cytoplasmic domain of the TfR since Tf10 exited cells with the same rate when bound to the wild-type TfR or a mutated receptor with only four amino acids in the cytoplasmic tail. Thus, cross-linking of surface receptors by a multivalent ligand acts as a lumenal retention signal within the recycling compartment. The data presented here show that the recycling compartment labeled by Tf10 is a long-lived organelle along the early endosome recycling pathway that remains fusion accessible to subsequently endocytosed Tf.",1995 Jun 2,,J Cell Biol,,,True
fcbb20fc325656ad86d5ed3e810cd0f4639ada77,PMC,Apoptotic signals induce specific degradation of ribosomal RNA in yeast,http://dx.doi.org/10.1093/nar/gkm1100,PMC2396418,18385160,CC BY-NC,"Organisms exposed to reactive oxygen species, generated endogenously during respiration or by environmental conditions, undergo oxidative stress. Stress response can either repair the damage or activate one of the programmed cell death (PCD) mechanisms, for example apoptosis, and finally end in cell death. One striking characteristic, which accompanies apoptosis in both vertebrates and yeast, is a fragmentation of cellular DNA and mammalian apoptosis is often associated with degradation of different RNAs. We show that in yeast exposed to stimuli known to induce apoptosis, such as hydrogen peroxide, acetic acid, hyperosmotic stress and ageing, two large subunit ribosomal RNAs, 25S and 5.8S, became extensively degraded with accumulation of specific intermediates that differ slightly depending on cell death conditions. This process is most likely endonucleolytic, is correlated with stress response, and depends on the mitochondrial respiratory status: rRNA is less susceptible to degradation in respiring cells with functional defence against oxidative stress. In addition, RNA fragmentation is independent of two yeast apoptotic factors, metacaspase Yca1 and apoptosis-inducing factor Aif1, but it relies on the apoptotic chromatin condensation induced by histone H2B modifications. These data describe a novel phenotype for certain stress- and ageing-related PCD pathways in yeast.",2008 May 1,"['Mroczek, Seweryn', 'Kufel, Joanna']",Nucleic Acids Res,,,True
c6ea09cae9a6185a84ab731e86257d6507f5a102,PMC,Inhibition of HIV-1 by multiple siRNAs expressed from a single microRNA polycistron,http://dx.doi.org/10.1093/nar/gkn109,PMC2396423,18346971,CC BY-NC,"RNA interference (RNAi) is a powerful approach to inhibit human immunodeficiency virus type 1 (HIV-1) replication. However, HIV-1 can escape from RNAi-mediated antiviral therapy by selection of mutations in the targeted sequence. To prevent viral escape, multiple small interfering RNAs (siRNAs) against conserved viral sequences should be combined. Ideally, these RNA inhibitors should be expressed simultaneously from a single transgene transcript. In this study, we tested a multiplex microRNA (miRNA) expression strategy by inserting multiple effective anti-HIV siRNA sequences in the miRNA polycistron mir-17-92. Individual anti-HIV miRNAs that resemble the natural miRNA structures were optimized by varying the siRNA position in the hairpin stem to obtain maximal effectiveness against luciferase reporters and HIV-1. We show that an antiviral miRNA construct can have a greater intrinsic inhibitory activity than a conventional short hairpin (shRNA) construct. When combined in a polycistron setting, the silencing activity of an individual miRNA is strongly boosted. We demonstrate that HIV-1 replication can be efficiently inhibited by simultaneous expression of four antiviral siRNAs from the polycistronic miRNA transcript. These combined results indicate that a multiplex miRNA strategy may be a promising therapeutic approach to attack escape-prone viral pathogens.",2008 May 16,"['Liu, Ying Poi', 'Haasnoot, Joost', 'ter Brake, Olivier', 'Berkhout, Ben', 'Konstantinova, Pavlina']",Nucleic Acids Res,,,True
32f0f51772fb98f4cdf1a9c3ba578b86e75d79cc,PMC,Cytoprotective Activity of Glycyrrhizae radix Extract Against Arsenite-induced Cytotoxicity,http://dx.doi.org/10.1093/ecam/nem014,PMC2396482,18604262,CC BY-NC,"Licorice, Glycyrrhizae radix, is one of the herbal medicines in East Asia that has been commonly used for treating various diseases, including stomach disorders. This study investigated the effect of licorice on arsenite (As)-induced cytotoxicity in H4IIE cells, a rat hepatocyte-derived cell line. Cell viability was significantly diminished in As-treated H4IIE cells in a time and concentration-dependent manner. Furthermore, results from flow cytometric assay and DNA laddering in H4IIE cells showed that As treatment induced apoptotic cell death by activating caspase-3. Licorice (0.1 and 1.0 mg ml(−1)) treatment significantly inhibited cell death and the activity of caspase-3 in response to As exposure. These results demonstrate that licorice induced a cytoprotective effect against As-induced cell death by inhibition of caspase-3.",2008 Jun 25,"['Kim, Sang Chan', 'Park, Sook Jahr', 'Lee, Jong Rok', 'Seo, Jung Cheol', 'Yang, Chae Ha', 'Byun, Sung Hui']",Evid Based Complement Alternat Med,,,True
fa9460f462e92e3ccbecc0e9fe406b886b7c1e35,PMC,The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil,http://dx.doi.org/10.1038/emboj.2008.101,PMC2396876,18497748,CC BY-NC-ND,"Moraxella catarrhalis is a ubiquitous human-specific bacterium commonly associated with upper and lower respiratory tract infections, including otitis media, sinusitis and chronic obstructive pulmonary disease. The bacterium uses an autotransporter protein UspA1 to target an important human cellular receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Using X-ray crystallography, we show that the CEACAM1 receptor-binding region of UspA1 unusually consists of an extended, rod-like left-handed trimeric coiled-coil. Mutagenesis and binding studies of UspA1 and the N-domain of CEACAM1 have been used to delineate the interacting surfaces between ligand and receptor and guide assembly of the complex. However, solution scattering, molecular modelling and electron microscopy analyses all indicate that significant bending of the UspA1 coiled-coil stalk also occurs. This explains how UspA1 can engage CEACAM1 at a site far distant from its head group, permitting closer proximity of the respective cell surfaces during infection.",2008 Jun 18,"['Conners, Rebecca', 'Hill, Darryl J', 'Borodina, Elena', 'Agnew, Christopher', 'Daniell, Sarah J', 'Burton, Nicholas M', 'Sessions, Richard B', 'Clarke, Anthony R', 'Catto, Lucy E', 'Lammie, Donna', 'Wess, Timothy', 'Brady, R Leo', 'Virji, Mumtaz']",EMBO J,,,True
1f9b3432b8fa207c7ee6b74432979c40d2af1458,PMC,The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil,http://dx.doi.org/10.1038/emboj.2008.101,PMC2396876,18497748,CC BY-NC-ND,"Moraxella catarrhalis is a ubiquitous human-specific bacterium commonly associated with upper and lower respiratory tract infections, including otitis media, sinusitis and chronic obstructive pulmonary disease. The bacterium uses an autotransporter protein UspA1 to target an important human cellular receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Using X-ray crystallography, we show that the CEACAM1 receptor-binding region of UspA1 unusually consists of an extended, rod-like left-handed trimeric coiled-coil. Mutagenesis and binding studies of UspA1 and the N-domain of CEACAM1 have been used to delineate the interacting surfaces between ligand and receptor and guide assembly of the complex. However, solution scattering, molecular modelling and electron microscopy analyses all indicate that significant bending of the UspA1 coiled-coil stalk also occurs. This explains how UspA1 can engage CEACAM1 at a site far distant from its head group, permitting closer proximity of the respective cell surfaces during infection.",2008 Jun 18,"['Conners, Rebecca', 'Hill, Darryl J', 'Borodina, Elena', 'Agnew, Christopher', 'Daniell, Sarah J', 'Burton, Nicholas M', 'Sessions, Richard B', 'Clarke, Anthony R', 'Catto, Lucy E', 'Lammie, Donna', 'Wess, Timothy', 'Brady, R Leo', 'Virji, Mumtaz']",EMBO J,,,False
41be78abddf11e2c661bb99fabae20b00a846752,PMC,The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil,http://dx.doi.org/10.1038/emboj.2008.101,PMC2396876,18497748,CC BY-NC-ND,"Moraxella catarrhalis is a ubiquitous human-specific bacterium commonly associated with upper and lower respiratory tract infections, including otitis media, sinusitis and chronic obstructive pulmonary disease. The bacterium uses an autotransporter protein UspA1 to target an important human cellular receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Using X-ray crystallography, we show that the CEACAM1 receptor-binding region of UspA1 unusually consists of an extended, rod-like left-handed trimeric coiled-coil. Mutagenesis and binding studies of UspA1 and the N-domain of CEACAM1 have been used to delineate the interacting surfaces between ligand and receptor and guide assembly of the complex. However, solution scattering, molecular modelling and electron microscopy analyses all indicate that significant bending of the UspA1 coiled-coil stalk also occurs. This explains how UspA1 can engage CEACAM1 at a site far distant from its head group, permitting closer proximity of the respective cell surfaces during infection.",2008 Jun 18,"['Conners, Rebecca', 'Hill, Darryl J', 'Borodina, Elena', 'Agnew, Christopher', 'Daniell, Sarah J', 'Burton, Nicholas M', 'Sessions, Richard B', 'Clarke, Anthony R', 'Catto, Lucy E', 'Lammie, Donna', 'Wess, Timothy', 'Brady, R Leo', 'Virji, Mumtaz']",EMBO J,,,False
3c5da25cc520e0f35dcc904b7fa8a224cf37320d,PMC,The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil,http://dx.doi.org/10.1038/emboj.2008.101,PMC2396876,18497748,CC BY-NC-ND,"Moraxella catarrhalis is a ubiquitous human-specific bacterium commonly associated with upper and lower respiratory tract infections, including otitis media, sinusitis and chronic obstructive pulmonary disease. The bacterium uses an autotransporter protein UspA1 to target an important human cellular receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Using X-ray crystallography, we show that the CEACAM1 receptor-binding region of UspA1 unusually consists of an extended, rod-like left-handed trimeric coiled-coil. Mutagenesis and binding studies of UspA1 and the N-domain of CEACAM1 have been used to delineate the interacting surfaces between ligand and receptor and guide assembly of the complex. However, solution scattering, molecular modelling and electron microscopy analyses all indicate that significant bending of the UspA1 coiled-coil stalk also occurs. This explains how UspA1 can engage CEACAM1 at a site far distant from its head group, permitting closer proximity of the respective cell surfaces during infection.",2008 Jun 18,"['Conners, Rebecca', 'Hill, Darryl J', 'Borodina, Elena', 'Agnew, Christopher', 'Daniell, Sarah J', 'Burton, Nicholas M', 'Sessions, Richard B', 'Clarke, Anthony R', 'Catto, Lucy E', 'Lammie, Donna', 'Wess, Timothy', 'Brady, R Leo', 'Virji, Mumtaz']",EMBO J,,,False
e347968f79247bf06e8b960e64f65f75ec02bcc2,PMC,The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil,http://dx.doi.org/10.1038/emboj.2008.101,PMC2396876,18497748,CC BY-NC-ND,"Moraxella catarrhalis is a ubiquitous human-specific bacterium commonly associated with upper and lower respiratory tract infections, including otitis media, sinusitis and chronic obstructive pulmonary disease. The bacterium uses an autotransporter protein UspA1 to target an important human cellular receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Using X-ray crystallography, we show that the CEACAM1 receptor-binding region of UspA1 unusually consists of an extended, rod-like left-handed trimeric coiled-coil. Mutagenesis and binding studies of UspA1 and the N-domain of CEACAM1 have been used to delineate the interacting surfaces between ligand and receptor and guide assembly of the complex. However, solution scattering, molecular modelling and electron microscopy analyses all indicate that significant bending of the UspA1 coiled-coil stalk also occurs. This explains how UspA1 can engage CEACAM1 at a site far distant from its head group, permitting closer proximity of the respective cell surfaces during infection.",2008 Jun 18,"['Conners, Rebecca', 'Hill, Darryl J', 'Borodina, Elena', 'Agnew, Christopher', 'Daniell, Sarah J', 'Burton, Nicholas M', 'Sessions, Richard B', 'Clarke, Anthony R', 'Catto, Lucy E', 'Lammie, Donna', 'Wess, Timothy', 'Brady, R Leo', 'Virji, Mumtaz']",EMBO J,,,False
65a29504e9fb777dea5b6642112095999a8892ec,PMC,The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil,http://dx.doi.org/10.1038/emboj.2008.101,PMC2396876,18497748,CC BY-NC-ND,"Moraxella catarrhalis is a ubiquitous human-specific bacterium commonly associated with upper and lower respiratory tract infections, including otitis media, sinusitis and chronic obstructive pulmonary disease. The bacterium uses an autotransporter protein UspA1 to target an important human cellular receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Using X-ray crystallography, we show that the CEACAM1 receptor-binding region of UspA1 unusually consists of an extended, rod-like left-handed trimeric coiled-coil. Mutagenesis and binding studies of UspA1 and the N-domain of CEACAM1 have been used to delineate the interacting surfaces between ligand and receptor and guide assembly of the complex. However, solution scattering, molecular modelling and electron microscopy analyses all indicate that significant bending of the UspA1 coiled-coil stalk also occurs. This explains how UspA1 can engage CEACAM1 at a site far distant from its head group, permitting closer proximity of the respective cell surfaces during infection.",2008 Jun 18,"['Conners, Rebecca', 'Hill, Darryl J', 'Borodina, Elena', 'Agnew, Christopher', 'Daniell, Sarah J', 'Burton, Nicholas M', 'Sessions, Richard B', 'Clarke, Anthony R', 'Catto, Lucy E', 'Lammie, Donna', 'Wess, Timothy', 'Brady, R Leo', 'Virji, Mumtaz']",EMBO J,,,True
0f2e41a966ec7d622762dc64ba63009e00a69bd5,PMC,Rapid discovery and optimization of therapeutic antibodies against emerging infectious diseases,http://dx.doi.org/10.1093/protein/gzn027,PMC2461042,18480090,CC BY-NC,"Using a comprehensive set of discovery and optimization tools, antibodies were produced with the ability to neutralize SARS coronavirus (SARS-CoV) infection in Vero E6 cells and in animal models. These anti-SARS antibodies were discovered using a novel DNA display method, which can identify new antibodies within days. Once neutralizing antibodies were identified, a comprehensive and effective means of converting the mouse sequences to human frameworks was accomplished using HuFR™ (human framework reassembly) technology. The best variant (61G4) from this screen showed a 3.5–4-fold improvement in neutralization of SARS-CoV infection in vitro. Finally, using a complete site-saturation mutagenesis methodology focused on the CDR (complementarity determining regions), a single point mutation (51E7) was identified that improved the 80% plaque reduction neutralization of the virus by greater than 8-fold. These discovery and evolution strategies can be applied to any emerging pathogen or toxin where a causative agent is known.",2008 Aug 13,"['Rogers, J.', 'Schoepp, R.J.', 'Schröder, O.', 'Clements, T.L.', 'Holland, T.F.', 'Li, J.Q.', 'Li, J.', 'Lewis, L.M.', 'Dirmeier, R.P.', 'Frey, G.J.', 'Tan, X.', 'Wong, K.', 'Woodnutt, G.', 'Keller, M.', 'Reed, D.S.', 'Kimmel, B.E.', 'Tozer, E.C.']",Protein Eng Des Sel,,,True
d0c1b37380fd7838db1f135fd702c8fd0cd67361,PMC,"Data-driven exploration of ‘spatial pattern-time process-driving forces’ associations of SARS epidemic in Beijing, China",http://dx.doi.org/10.1093/pubmed/fdn023,PMC2518065,18441347,CC BY-NC,"BACKGROUND: Severe Acute Respiratory Syndrome (SARS) was first reported in November 2002 in China, and spreads to about 30 countries over the next few months. While the characteristics of epidemic transmission are individually assessed, there are also important implicit associations between them. METHODS: A novel methodological framework was developed to overcome barriers among separate epidemic statistics and identify distinctive SARS features. Individual statistics were pair-wise linked in terms of their common features, and an integrative epidemic network was formulated. RESULTS: The study of associations between important SARS characteristics considerably enhanced the mainstream epidemic analysis and improved the understanding of the relationships between the observed epidemic determinants. The response of SARS transmission to various epidemic control factors was simulated, target areas were detected, critical time and relevant factors were determined. CONCLUSION: It was shown that by properly accounting for links between different SARS statistics, a data-based analysis can efficiently reveal systematic associations between epidemic determinants. The analysis can predict the temporal trend of the epidemic given its spatial pattern, to estimate spatial exposure given temporal evolution, and to infer the driving forces of SARS transmission given the spatial exposure distribution.",2008 Sep 26,"['Wang, Jin-Feng', 'Christakos, George', 'Han, Wei-Guo', 'Meng, Bin']",J Public Health (Oxf),,,True
0caa109e0faf5c5fefe81a8108e1199058cb3a27,PMC,"An Evaluation of the Additive Effect of Natural Herbal Medicine on SARS or SARS-like Infectious Diseases in 2003: A Randomized, Double-blind, and Controlled Pilot Study",http://dx.doi.org/10.1093/ecam/nem035,PMC2529389,18830453,CC BY-NC,"Natural herbal medicine (NHM) has been used to control infectious diseases for thousands of years. In view of the possible beneficial effect of NHM on SARS, we conducted this study to examine whether NHM is of any benefit as a supplementary treatment of SARS or SARS-like infectious disease. This was a randomized, double-blind, placebo-controlled trial. Twenty-eight patients fulfilled the WHO inclusion criteria and our exclusion criteria. All enrolled patients received routine western-medicine treatment. Patients were randomly allocated to one of the three supplementary treatment groups: NHM A (Group A, n = 9) NHM B (Group B, n = 9) or placebo (Group C, n = 10). Chest X-ray was done every 1 or 2 days for every patient. Reading radiologists use a standard 0–3 scoring system (0: no infiltration; 1: focal haziness or even small patchy lesion; 2: ground glass picture; 3: lobar consolidation) according to the severity of infiltration in each lung field (three lung fields in both right and left lungs). The main outcome measurements were the improving chest radiographic scores (IRS) and the duration (days) till improvement (DI). One patient from the placebo group passed away. Patients from NHM A took less days before showing improvement (6.7 ± 1.8) compared with placebo group (11.2 ± 4.9), which showed statistical significance (P = 0.04). The cases were too few to be conclusive, the initial observations seem to indicate NHM appears to be safe in non-criticallly ill patients and clinical trials are feasible in the setting of pandemic outbreaks.",2008 Sep 29,"['Hsu, Chung-Hua', 'Hwang, Kung-Chang', 'Chao, Chung-Liang', 'Chang, Steve G. N.', 'Ho, Mei-Shang', 'Lin, Jaung-Geng', 'Chang, Hen-Hong', 'Kao, Shung-Te', 'Chen, Yi-Ming', 'Chou, Pesus']",Evid Based Complement Alternat Med,,,True
13f67fd2f646199f7deed8d013bce39056332123,PMC,Studying copy number variations using a nanofluidic platform,http://dx.doi.org/10.1093/nar/gkn518,PMC2566873,18710881,CC BY-NC,"Copy number variations (CNVs) in the human genome are conventionally detected using high-throughput scanning technologies, such as comparative genomic hybridization and high-density single nucleotide polymorphism (SNP) microarrays, or relatively low-throughput techniques, such as quantitative polymerase chain reaction (PCR). All these approaches are limited in resolution and can at best distinguish a twofold (or 50%) difference in copy number. We have developed a new technology to study copy numbers using a platform known as the digital array, a nanofluidic biochip capable of accurately quantitating genes of interest in DNA samples. We have evaluated the digital array's performance using a model system, to show that this technology is exquisitely sensitive, capable of differentiating as little as a 15% difference in gene copy number (or between 6 and 7 copies of a target gene). We have also analyzed commercial DNA samples for their CYP2D6 copy numbers and confirmed that our results were consistent with those obtained independently using conventional techniques. In a screening experiment with breast cancer and normal DNA samples, the ERBB2 gene was found to be amplified in about 35% of breast cancer samples. The use of the digital array enables accurate measurement of gene copy numbers and is of significant value in CNV studies.",2008 Oct 18,"['Qin, Jian', 'Jones, Robert C.', 'Ramakrishnan, Ramesh']",Nucleic Acids Res,,,False
cc11d6ace6db8abceb7213e6b37d93ce5417f696,PMC,Studying copy number variations using a nanofluidic platform,http://dx.doi.org/10.1093/nar/gkn518,PMC2566873,18710881,CC BY-NC,"Copy number variations (CNVs) in the human genome are conventionally detected using high-throughput scanning technologies, such as comparative genomic hybridization and high-density single nucleotide polymorphism (SNP) microarrays, or relatively low-throughput techniques, such as quantitative polymerase chain reaction (PCR). All these approaches are limited in resolution and can at best distinguish a twofold (or 50%) difference in copy number. We have developed a new technology to study copy numbers using a platform known as the digital array, a nanofluidic biochip capable of accurately quantitating genes of interest in DNA samples. We have evaluated the digital array's performance using a model system, to show that this technology is exquisitely sensitive, capable of differentiating as little as a 15% difference in gene copy number (or between 6 and 7 copies of a target gene). We have also analyzed commercial DNA samples for their CYP2D6 copy numbers and confirmed that our results were consistent with those obtained independently using conventional techniques. In a screening experiment with breast cancer and normal DNA samples, the ERBB2 gene was found to be amplified in about 35% of breast cancer samples. The use of the digital array enables accurate measurement of gene copy numbers and is of significant value in CNV studies.",2008 Oct 18,"['Qin, Jian', 'Jones, Robert C.', 'Ramakrishnan, Ramesh']",Nucleic Acids Res,,,True
932e14a57e47e0995288cc330055b48b06bbd74b,PMC,KnotInFrame: prediction of −1 ribosomal frameshift events,http://dx.doi.org/10.1093/nar/gkn578,PMC2566878,18820303,CC BY-NC,"Programmed −1 ribosomal frameshift (−1 PRF) allows for alternative reading frames within one mRNA. First found in several viruses, it is now believed to exist in all kingdoms of life. Strong stimulators for −1 PRF are a heptameric slippery site and an RNA pseudoknot. Here, we present a new algorithm KnotInFrame, for the automatic detection of −1 PRF signals from genomic sequences. It finds the frameshifting stimulators by means of a specialized RNA-pseudoknot folding program, fast enough for genome-wide analyses. Evaluations on known −1 PRF signals demonstrate a high sensitivity.",2008 Oct 27,"['Theis, Corinna', 'Reeder, Jens', 'Giegerich, Robert']",Nucleic Acids Res,,,False
14c9ca5bf096d03bde8e8ffe88c7419ef5b79b13,PMC,KnotInFrame: prediction of −1 ribosomal frameshift events,http://dx.doi.org/10.1093/nar/gkn578,PMC2566878,18820303,CC BY-NC,"Programmed −1 ribosomal frameshift (−1 PRF) allows for alternative reading frames within one mRNA. First found in several viruses, it is now believed to exist in all kingdoms of life. Strong stimulators for −1 PRF are a heptameric slippery site and an RNA pseudoknot. Here, we present a new algorithm KnotInFrame, for the automatic detection of −1 PRF signals from genomic sequences. It finds the frameshifting stimulators by means of a specialized RNA-pseudoknot folding program, fast enough for genome-wide analyses. Evaluations on known −1 PRF signals demonstrate a high sensitivity.",2008 Oct 27,"['Theis, Corinna', 'Reeder, Jens', 'Giegerich, Robert']",Nucleic Acids Res,,,True
7d7bab4809a66048899e1e95227eb5d72e46818f,PMC,Unifying evolutionary and thermodynamic information for RNA folding of multiple alignments,http://dx.doi.org/10.1093/nar/gkn544,PMC2582601,18836192,CC BY-NC,"Computational methods for determining the secondary structure of RNA sequences from given alignments are currently either based on thermodynamic folding, compensatory base pair substitutions or both. However, there is currently no approach that combines both sources of information in a single optimization problem. Here, we present a model that formally integrates both the energy-based and evolution-based approaches to predict the folding of multiple aligned RNA sequences. We have implemented an extended version of Pfold that identifies base pairs that have high probabilities of being conserved and of being energetically favorable. The consensus structure is predicted using a maximum expected accuracy scoring scheme to smoothen the effect of incorrectly predicted base pairs. Parameter tuning revealed that the probability of base pairing has a higher impact on the RNA structure prediction than the corresponding probability of being single stranded. Furthermore, we found that structurally conserved RNA motifs are mostly supported by folding energies. Other problems (e.g. RNA-folding kinetics) may also benefit from employing the principles of the model we introduce. Our implementation, PETfold, was tested on a set of 46 well-curated Rfam families and its performance compared favorably to that of Pfold and RNAalifold.",2008 Nov 4,"['Seemann, Stefan E.', 'Gorodkin, Jan', 'Backofen, Rolf']",Nucleic Acids Res,,,True
0e1c055e39c45d7cef611b6bd17fb67c249ed742,PMC,Unifying evolutionary and thermodynamic information for RNA folding of multiple alignments,http://dx.doi.org/10.1093/nar/gkn544,PMC2582601,18836192,CC BY-NC,"Computational methods for determining the secondary structure of RNA sequences from given alignments are currently either based on thermodynamic folding, compensatory base pair substitutions or both. However, there is currently no approach that combines both sources of information in a single optimization problem. Here, we present a model that formally integrates both the energy-based and evolution-based approaches to predict the folding of multiple aligned RNA sequences. We have implemented an extended version of Pfold that identifies base pairs that have high probabilities of being conserved and of being energetically favorable. The consensus structure is predicted using a maximum expected accuracy scoring scheme to smoothen the effect of incorrectly predicted base pairs. Parameter tuning revealed that the probability of base pairing has a higher impact on the RNA structure prediction than the corresponding probability of being single stranded. Furthermore, we found that structurally conserved RNA motifs are mostly supported by folding energies. Other problems (e.g. RNA-folding kinetics) may also benefit from employing the principles of the model we introduce. Our implementation, PETfold, was tested on a set of 46 well-curated Rfam families and its performance compared favorably to that of Pfold and RNAalifold.",2008 Nov 4,"['Seemann, Stefan E.', 'Gorodkin, Jan', 'Backofen, Rolf']",Nucleic Acids Res,,,True
1a7676018fd73150a122c2afb1362324dbab4918,PMC,A sensitive array-based assay for identifying multiple TMPRSS2:ERG fusion gene variants,http://dx.doi.org/10.1093/nar/gkn585,PMC2582611,18794177,CC BY-NC,"Studies of gene fusions in solid tumors are not as extensive as in hematological malignancies due to several technical and analytical problems associated with tumor heterogeneity. Nevertheless, there is a growing interest in the role of fusion genes in common epithelial tumors after the discovery of recurrent TMPRSS2:ETS fusions in prostate cancer. Among all of the reported fusion partners in the ETS gene family, TMPRSS2:ERG is the most prevalent one. Here, we present a simple and sensitive microarray-based assay that is able to simultaneously determine multiple fusion variants with a single RT–PCR in impure RNA specimens. The assay detected TMPRSS2:ERG fusion transcripts with a detection sensitivity of <10 cells in the presence of more than 3000 times excess normal RNA, and in primary prostate tumors having no >1% of cancer cells. The ability to detect multiple transcript variants in a single assay is critically dependent on both the primer and probe designs. The assay should facilitate clinical and basic studies for fusion gene screening in clinical specimens, as it can be readily adapted to include multiple gene loci.",2008 Nov 15,"['Lu, Qing', 'Nunez, Esperanza', 'Lin, Chunrun', 'Christensen, Kimberly', 'Downs, Tracy', 'Carson, Dennis A.', 'Wang-Rodriguez, Jessica', 'Liu, Yu-Tsueng']",Nucleic Acids Res,,,True
d6ce322684cccda1ff72e7dacf22da2259cf65c6,PMC,Delivery of steric block morpholino oligomers by (R-X-R)(4) peptides: structure–activity studies,http://dx.doi.org/10.1093/nar/gkn541,PMC2582615,18796528,CC BY-NC,"Redirecting the splicing machinery through the hybridization of high affinity, RNase H- incompetent oligonucleotide analogs such as phosphoramidate morpholino oligonucleotides (PMO) might lead to important clinical applications. Chemical conjugation of PMO to arginine-rich cell penetrating peptides (CPP) such as (R-Ahx-R)(4) (with Ahx standing for 6-aminohexanoic acid) leads to sequence-specific splicing correction in the absence of endosomolytic agents in cell culture at variance with most conventional CPPs. Importantly, (R-Ahx-R)(4)–PMO conjugates are effective in mouse models of various viral infections and Duchenne muscular dystrophy. Unfortunately, active doses in some applications might be close to cytotoxic ones thus presenting challenge for systemic administration of the conjugates in those clinical settings. Structure–activity relationship studies have thus been undertaken to unravel CPP structural features important for the efficient nuclear delivery of the conjugated PMO and limiting steps in their internalization pathway. Affinity for heparin (taken as a model heparan sulfate), hydrophobicity, cellular uptake, intracellular distribution and splicing correction have been monitored. Spacing between the charges, hydrophobicity of the linker between the Arg-groups and Arg-stereochemistry influence splicing correction efficiency. A significant correlation between splicing correction efficiency, affinity for heparin and ability to destabilize model synthetic vesicles has been observed but no correlation with cellular uptake has been found. Efforts will have to focus on endosomal escape since it appears to remain the limiting factor for the delivery of these splice-redirecting ON analogs.",2008 Nov 16,"['Abes, Rachida', 'Moulton, Hong M.', 'Clair, Philippe', 'Yang, Sung-Tae', 'Abes, Said', 'Melikov, Kamran', 'Prevot, Paul', 'Youngblood, Derek S.', 'Iversen, Patrick L.', 'Chernomordik, Leonid V.', 'Lebleu, Bernard']",Nucleic Acids Res,,,True
7c8829abbf6087d8a19a616952acf92bb76dc38d,PMC,A Correlation between the Severity of Lung Lesions on Radiographs and Clinical Findings in Patients with Severe Acute Respiratory Syndrome,http://dx.doi.org/10.3348/kjr.2007.8.6.466,PMC2627448,18071276,CC BY-NC,"OBJECTIVE: The purpose of this study was to quantify lesions on chest radiographs in patients with severe acute respiratory syndrome (SARS) and analyze the severity of the lesions with clinical parameters. MATERIALS AND METHODS: Two experienced radiologists reviewed chest radiographs of 28 patients with SARS. Each lung was divided into upper, middle, and lower zones. A SARS-related lesion in each zone was scored using a four-point scale: zero to three. The mean and maximal radiographic scores were analyzed statistically to determine if the scorings were related to the laboratory data and clinical course. RESULTS: Forward stepwise multiple linear regression showed that the mean radiographic score correlated most significantly with the number of hospitalized days (p < 0.001). The second most significant factor was the absolute lymphocyte count (p < 0.001) and the third most significant factor was the number of days of intubation (p = 0.025). The maximal radiographic score correlated best with the percentage of lymphocytes in a leukocyte count (p < 0.001), while the second most significant factor was the number of hospitalized days (p < 0.001) and the third most significant factor was the absolute lymphocyte count (p = 0.013). The mean radiographic scores of the patients who died, with comorbidities and without a comorbidity were 11.1, 6.3 and 2.9, respectively (p = 0.032). The corresponding value for maximal radiographic scores were 17.7, 9.7 and 6.0, respectively (p = 0.033). CONCLUSION: The severity of abnormalities quantified on chest radiographs in patients with SARS correlates with the clinical parameters.",2007 Dec 20 Nov-Dec,"['Wan, Yung-Liang', 'Tsay, Pei-Kwei', 'Cheung, Yun-Chung', 'Chiang, Ping-Cherng', 'Wang, Chun-Hua', 'Tsai, Ying-Huang', 'Kuo, Han-Ping', 'Tsao, Kuo-Chien', 'Lin, Tzou-Yien']",Korean J Radiol,,,True
12d3e24cd2d11b34cd6ec3e6851868c67f891f13,PMC,Avian Influenza: Should China Be Alarmed?,http://dx.doi.org/10.3349/ymj.2007.48.4.586,PMC2628066,17722229,CC BY-NC,"Avian influenza has emerged as one of the primary public health concern of the 21st century. Influenza strain H5N1 is capable of incidentally infecting humans and other mammals. Since their reemergence in 2003, highly pathogenic avian influenza A (H5N1) viruses have been transmitted from poultry to humans (by direct or indirect contact with infected birds) in several provinces of Mainland China, which has resulted in 22 cases of human infection and has created repercussions for the Chinese economy. People have been concerned whether a new pandemic will occur in the future. The eradication of pathogenic avian influenza viruses appears to be the most effective way to prevent an influenza pandemic. This paper will examine the features of H5N1, including incidence, infection, immunity, clinical management, prevention and control, and therapy in Mainland China.",2007 Aug 31,"['Su, Zhaoliang', 'Xu, Huaxi', 'Chen, Jianguo']",Yonsei Med J,,,False
eb627ab77c71445ccc0b05f2193fe9289ac142ee,PMC,Protein Domain Boundary Predictions: A Structural Biology Perspective,http://dx.doi.org/10.2174/1874091X00903010001,PMC2669640,19401756,CC BY-NC,"One of the important fields to apply computational tools for domain boundaries prediction is structural biology. They can be used to design protein constructs that must be expressed in a stable and functional form and must produce diffraction-quality crystals. However, prediction of protein domain boundaries on the basis of amino acid sequences is still very problematical. In present study the performance of several computational approaches are compared. It is observed that the statistical significance of most of the predictions is rather poor. Nevertheless, when the right number of domains is correctly predicted, domain boundaries are predicted within very few residues from their real location. It can be concluded that prediction methods cannot be used yet as routine tools in structural biology, though some of them are rather promising.",2009 Jan 21,"['Kirillova, Svetlana', 'Kumar, Suresh', 'Carugo, Oliviero']",Open Biochem J,,,True
f64a7539cff0d59ff66885154be0f6d105e4a3ad,PMC,VirHostNet: a knowledge base for the management and the analysis of proteome-wide virus–host interaction networks,http://dx.doi.org/10.1093/nar/gkn794,PMC2686459,18984613,CC BY-NC,"Infectious diseases caused by viral agents kill millions of people every year. The improvement of prevention and treatment of viral infections and their associated diseases remains one of the main public health challenges. Towards this goal, deciphering virus–host molecular interactions opens new perspectives to understand the biology of infection and for the design of new antiviral strategies. Indeed, modelling of an infection network between viral and cellular proteins will provide a conceptual and analytic framework to efficiently formulate new biological hypothesis at the proteome scale and to rationalize drug discovery. Therefore, we present the first release of VirHostNet (Virus–Host Network), a public knowledge base specialized in the management and analysis of integrated virus–virus, virus–host and host–host interaction networks coupled to their functional annotations. VirHostNet integrates an extensive and original literature-curated dataset of virus–virus and virus–host interactions (2671 non-redundant interactions) representing more than 180 distinct viral species and one of the largest human interactome (10 672 proteins and 68 252 non-redundant interactions) reconstructed from publicly available data. The VirHostNet Web interface provides appropriate tools that allow efficient query and visualization of this infected cellular network. Public access to the VirHostNet knowledge-based system is available at http://pbildb1.univ-lyon1.fr/virhostnet.",2009 Jan 4,"['Navratil, Vincent', 'de Chassey, Benoît', 'Meyniel, Laurène', 'Delmotte, Stéphane', 'Gautier, Christian', 'André, Patrice', 'Lotteau, Vincent', 'Rabourdin-Combe, Chantal']",Nucleic Acids Res,,,True
f6b6ab22699e8c898e0de1614c8ce506ce99dd8a,PMC,Rfam: updates to the RNA families database,http://dx.doi.org/10.1093/nar/gkn766,PMC2686503,18953034,CC BY-NC,"Rfam is a collection of RNA sequence families, represented by multiple sequence alignments and covariance models (CMs). The primary aim of Rfam is to annotate new members of known RNA families on nucleotide sequences, particularly complete genomes, using sensitive BLAST filters in combination with CMs. A minority of families with a very broad taxonomic range (e.g. tRNA and rRNA) provide the majority of the sequence annotations, whilst the majority of Rfam families (e.g. snoRNAs and miRNAs) have a limited taxonomic range and provide a limited number of annotations. Recent improvements to the website, methodologies and data used by Rfam are discussed. Rfam is freely available on the Web at http://rfam.sanger.ac.uk/and http://rfam.janelia.org/.",2009 Jan 25,"['Gardner, Paul P.', 'Daub, Jennifer', 'Tate, John G.', 'Nawrocki, Eric P.', 'Kolbe, Diana L.', 'Lindgreen, Stinus', 'Wilkinson, Adam C.', 'Finn, Robert D.', 'Griffiths-Jones, Sam', 'Eddy, Sean R.', 'Bateman, Alex']",Nucleic Acids Res,,,True
9427765d1870e8f4acfb6556a78f297e19068464,PMC,The RNA Virus Database,http://dx.doi.org/10.1093/nar/gkn729,PMC2686580,18948277,CC BY-NC,http://virus.zoo.ox.ac.uk/rnavirusdb; http://hivweb.sanbi.ac.za/rnavirusdb; http://bioinf.cs.auckland.ac.nz/rnavirusdb; http://tree.bio.ed.ac.uk/rnavirusdb.,2009 Jan 23,"['Belshaw, Robert', 'de Oliveira, Tulio', 'Markowitz, Sidney', 'Rambaut, Andrew']",Nucleic Acids Res,,,True
ff34c772e37156609477e7f0fa4aba793171f806,PMC,Climate Change and Health in Canada,,PMC2687921,19753294,CC BY-NC-ND,,2009 Jan,"Ford, Lea Berrang",Mcgill J Med,,,True
551d200fafe21b575108018aeb0f39b995c99dce,PMC,"IS HUMAN RIGHTS PREPARED? RISK, RIGHTS AND PUBLIC HEALTH EMERGENCIES",http://dx.doi.org/10.1093/medlaw/fwp007,PMC2697855,19429684,CC BY-NC,,2009 May 8 Summer,"['Murphy, Thérèse', 'Whitty, Noel']",Med Law Rev,,,True
4be09649912765a96eb17e54d40b4b777b3413c6,PMC,The pig as a mixing vessel for influenza viruses: Human and veterinary implications,,PMC2702078,19565018,CC BY-NC,"Influenza A viruses are highly infectious respiratory pathogens that can infect many species. Birds are the reservoir for all known influenza A subtypes; and novel influenza viruses can emerge from birds and infect mammalian species including humans. Because swine are susceptible to infection with both avian and human influenza viruses, novel reassortant influenza viruses can be generated in this mammalian species by reassortment of influenza viral segments leading to the “mixing vessel” theory. There is no direct evidence that the reassortment events culminating in the 1918, 1957 or 1968 pandemic influenza viruses originated from pigs. Genetic reassortment among avian, human and/or swine influenza virus gene segments has occurred in pigs and some novel reassortant swine viruses have been transmitted to humans. Notably, novel reassortant H2N3 influenza viruses isolated from the US pigs, most likely infected with avian influenza viruses through surface water collected in ponds for cleaning barns and watering animals, had a similar genetic make-up to early isolates (1957) of the H2N2 human pandemic. These novel H2N3 swine viruses were able to cause disease in swine and mice and were infectious and highly transmissible in swine and ferrets without prior adaptation. The preceding example shows that pigs could transmit novel viruses from an avian reservoir to other mammalian species. Importantly, H2 viruses pose a substantial risk to humans because they have been absent from mammalian species since 1968 and people born after 1968 have little preexisting immunity to the H2 subtype. It is difficult to predict which virus will cause the next human pandemic and when that pandemic might begin. Importantly, the establishment and spread of a reassorted mammalian-adapted virus from pigs to humans could happen anywhere in the world. Therefore, both human and veterinary research needs to give more attention to potential cross-species transmission capacity of influenza A viruses.",2008 Nov 27,"['Ma, Wenjun', 'Kahn, Robert E', 'Richt, Juergen A']",J Mol Genet Med,,,True
b411e12b20d883ef2ee5ca19d48eff9fccedf05f,PMC,CVTree update: a newly designed phylogenetic study platform using composition vectors and whole genomes,http://dx.doi.org/10.1093/nar/gkp278,PMC2703908,19398429,CC BY-NC,"The CVTree web server (http://tlife.fudan.edu.cn/cvtree) presented here is a new implementation of the whole genome-based, alignment-free composition vector (CV) method for phylogenetic analysis. It is more efficient and user-friendly than the previously published version in the 2004 web server issue of Nucleic Acids Research. The development of whole genome-based alignment-free CV method has provided an independent verification to the traditional phylogenetic analysis based on a single gene or a few genes. This new implementation attempts to meet the challenge of ever increasing amount of genome data and includes in its database more than 850 prokaryotic genomes which will be updated monthly from NCBI, and more than 80 fungal genomes collected manually from several sequencing centers. This new CVTree web server provides a faster and stable research platform. Users can upload their own sequences to find their phylogenetic position among genomes selected from the server's; inbuilt database. All sequence data used in a session may be downloaded as a compressed file. In addition to standard phylogenetic trees, users can also choose to output trees whose monophyletic branches are collapsed to various taxonomic levels. This feature is particularly useful for comparing phylogeny with taxonomy when dealing with thousands of genomes.",2009 Jul 1,"['Xu, Zhao', 'Hao, Bailin']",Nucleic Acids Res,,,True
d1f933dc26c6379a87598a2954792f4943c6c426,PMC,A Microarray Based Approach for the Identification of Common Foodborne Viruses,http://dx.doi.org/10.2174/1874357900903010007,PMC2707758,19718237,CC BY-NC,"An oligonucleotide array (microarray) incorporating 13,000 elements representing selected strains of hepatitis A virus (HAV), human coxsackieviruses A and B (CVA and CVB), genogroups I and II of Norovirus (NV), and human rotavirus (RV) gene segments 3,4,10, and 11 was designed based on the principle of tiling. Each oligonucleotide was 29 bases long, starting at every 5th base of every sequence, resulting in an overlap of 24 bases in two consecutive oligonucleotides. The applicability of the array for virus identification was examined using PCR amplified products from multiple HAV and CV strains. PCR products labeled with biotin were hybridized to the array, and the biotin was detected using a brief reaction with Cy3-labeled streptavidin, the array subjected to laser scanning, and the hybridization data plotted as fluorescence intensity against each oligonucleotide in the array. The combined signal intensities of all probes representing a particular strain of virus were calculated and plotted against all virus strains identified on a linear representation of the array. The profile of the total signal intensity identified the strain that is most likely represented in the amplified cDNA target. The results obtained with HAV and CV indicated that the hybridization profile thus generated can be used to identify closely related viral strains. This represents a significant improvement over current methods for virus identification using PCR amplification and amplicon sequencing.",2009 Mar 19,"['Ayodeji, Mobolanle', 'Kulka, Michael', 'Jackson, Scott A', 'Patel, Isha', 'Mammel, Mark', 'Cebula, Thomas A', 'Goswami, Biswendu B']",Open Virol J,,,True
eb2b6fa8f0d95869215b374ec24ad51490df4a61,PMC,SARS: How a global epidemic was stopped,http://dx.doi.org/10.3346/jkms.2006.21.5.963,PMC2722016,,CC BY-NC,,2006 Oct 31,"Peck, Kyong Ran",J Korean Med Sci,,,False
10663662f8b172088b8297c8fb32a529a00e6cee,PMC,Corticosteroids for pain relief in sore throat: systematic review and meta-analysis,http://dx.doi.org/10.1136/bmj.b2976,PMC2722696,19661138,CC BY-NC,"Objective To evaluate whether systemic corticosteroids improve symptoms of sore throat in adults and children. Design Systematic review and meta-analysis. Data sources Cochrane Central, Medline, Embase, Database of Reviews of Effectiveness (DARE), NHS Health Economics Database, and bibliographies. Outcome measures Percentage of patients with complete resolution at 24 and 48 hours, mean time to onset of pain relief, mean time to complete resolution of symptoms, days missed from work or school, recurrence, and adverse events. Results We included eight trials, consisting of 743 patients in total (369 children, 374 adults). 348 (47%) had exudative sore throat, and 330 (44%) were positive for group A β-haemolytic streptococcus. In addition to antibiotics and analgesia, corticosteroids significantly increased the likelihood of complete resolution of pain at 24 hours (four trials) by more than three times (relative risk 3.2, 95% confidence interval 2.0 to 5.1), and at 48 hours (three trials) to a lesser extent (1.7, 1.3 to 2.1). Corticosteroids (six trials) reduced mean time to onset of pain relief by more than 6 hours (95% confidence interval 3.4 to 9.3, P<0.001), although significant heterogeneity was present. The mean time to complete resolution was inconsistent across trials and a pooled analysis was not undertaken. Reporting of other outcomes was limited. Conclusions Corticosteroids provide symptomatic relief of pain in sore throat, in addition to antibiotic therapy, mainly in participants with severe or exudative sore throat.",2009 Aug 6,"['Hayward, Gail', 'Thompson, Matthew', 'Heneghan, Carl', 'Perera, Rafael', 'Del Mar, Chris', 'Glasziou, Paul']",BMJ,,,False
5322d3b9f5ee17d5b931f0c32173125d6a7304ed,PMC,Regulated Ire1-dependent decay of messenger RNAs in mammalian cells,http://dx.doi.org/10.1083/jcb.200903014,PMC2728407,19651891,CC BY-NC-SA,"Maintenance of endoplasmic reticulum (ER) function is achieved in part through Ire1 (inositol-requiring enzyme 1), a transmembrane protein activated by protein misfolding in the ER. The cytoplasmic nuclease domain of Ire1 cleaves the messenger RNA (mRNA) encoding XBP-1 (X-box–binding protein 1), enabling splicing and production of this active transcription factor. We recently showed that Ire1 activation independently induces the rapid turnover of mRNAs encoding membrane and secreted proteins in Drosophila melanogaster cells through a pathway we call regulated Ire1-dependent decay (RIDD). In this study, we show that mouse fibroblasts expressing wild-type Ire1 but not an Ire1 variant lacking nuclease activity also degrade mRNAs in response to ER stress. Using a second variant of Ire1 that is activated by a small adenosine triphosphate analogue, we show that although XBP-1 splicing can be artificially induced in the absence of ER stress, RIDD appears to require both Ire1 activity and ER stress. Our data suggest that cells use a multitiered mechanism by which different conditions in the ER lead to distinct outputs from Ire1.",2009 Aug 10,"['Hollien, Julie', 'Lin, Jonathan H.', 'Li, Han', 'Stevens, Nicole', 'Walter, Peter', 'Weissman, Jonathan S.']",J Cell Biol,,,True
1bfdb418d0771a30669663e4fa7bc18f5745d780,PMC,Insertion/Deletion Polymorphism of Angiotensin Converting Enzyme Gene in Kawasaki Disease,http://dx.doi.org/10.3346/jkms.2006.21.2.208,PMC2733992,16614502,CC BY-NC,"Polymorphism of angiotensin converting enzyme (ACE) gene is reported to be associated with ischemic heart disease, hypertrophic cardiomyopathy, and idiopathic dilated cardiomyopathy. In this study, we investigated the relationship between Kawasaki disease and insertion/deletion polymorphism of ACE gene. Fifty five Kawasaki disease patients and 43 healthy children were enrolled. ACE genotype was evaluated from each of the subjects' DNA fragments through polymerase chain reaction (PCR). Frequencies of ACE genotypes (DD, ID, II) were 12.7%, 60.0%, 27.3% in Kawasaki group, and 41.9%, 30.2%, 27.9% in control group respectively, indicating low rate of DD and high rate of ID genotype among Kawasaki patients (p<0.01). Comparing allelic (I, D) frequencies, I allele was more prevalent in Kawasaki group than in control group (57.3% vs. 43.0%, p<0.05). In Kawasaki group, both genotype and allelic frequencies were not statistically different between those with coronary dilatations and those without. ACE gene I/D polymorphism is thought to be associated with Kawasaki disease but not with the development of coronary dilatations.",2006 Apr 20,"['Shim, Yoon Hee', 'Kim, Hae Soon', 'Sohn, Sejung', 'Hong, Young Mi']",J Korean Med Sci,,,True
aae7a1522ae3ab5cb39cf204ab3d8ca7f9ac8ef8,PMC,A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP,http://dx.doi.org/10.1084/jem.20082874,PMC2737161,19652017,CC BY-NC-SA,"The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells. Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics. The cyclic dinucleotide cyclic-di–guanosine monophosphate (c-di-GMP) is a recently appreciated second messenger that plays critical regulatory roles in many species of bacteria but is not produced by eukaryotic cells. In vivo and in vitro studies have previously suggested that c-di-GMP is a potent immunostimulatory compound recognized by mouse and human cells. We provide evidence that c-di-GMP is sensed in the cytosol of mammalian cells via a novel immunosurveillance pathway. The potency of cytosolic signaling induced by c-di-GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, nuclear factor κB, and MAP kinases. However, the cytosolic pathway that senses c-di-GMP appears to be distinct from all known nucleic acid–sensing pathways. Our results suggest a novel mechanism by which host cells can induce an inflammatory response to a widely produced bacterial ligand.",2009 Aug 31,"['McWhirter, Sarah M.', 'Barbalat, Roman', 'Monroe, Kathryn M.', 'Fontana, Mary F.', 'Hyodo, Mamoru', 'Joncker, Nathalie T.', 'Ishii, Ken J.', 'Akira, Shizuo', 'Colonna, Marco', 'Chen, Zhijian J.', 'Fitzgerald, Katherine A.', 'Hayakawa, Yoshihiro', 'Vance, Russell E.']",J Exp Med,,,True
67595d2304315ae4af47ec96fbd42c55bd6855e2,PMC,ORMA: a tool for identification of species-specific variations in 16S rRNA gene and oligonucleotides design,http://dx.doi.org/10.1093/nar/gkp499,PMC2760787,19531738,CC BY-NC,"16S rRNA gene is one of the preferred targets for resolving species phylogenesis issues in microbiological-related contexts. However, the identification of single-nucleotide variations capable of distinguishing a sequence among a set of homologous ones can be problematic. Here we present ORMA (Oligonucleotide Retrieving for Molecular Applications), a set of scripts for discriminating positions search and for performing the selection of high-quality oligonucleotide probes to be used in molecular applications. Two assays based on Ligase Detection Reaction (LDR) are presented. First, a new set of probe pairs on cyanobacteria 16S rRNA sequences of 18 different species was compared to that of a previous study. Then, a set of LDR probe pairs for the discrimination of 13 pathogens contaminating bovine milk was evaluated. The software determined more than 100 candidate probe pairs per dataset, from more than 300 16S rRNA sequences, in less than 5 min. Results demonstrated how ORMA improved the performance of the LDR assay on cyanobacteria, correctly identifying 12 out of 14 samples, and allowed the perfect discrimination among the 13 milk pathogenic-related species. ORMA represents a significant improvement from other contexts where enzyme-based techniques have been employed on already known mutations of a single base or on entire subsequences.",2009 Sep 16,"['Severgnini, Marco', 'Cremonesi, Paola', 'Consolandi, Clarissa', 'Caredda, Giada', 'De Bellis, Gianluca', 'Castiglioni, Bianca']",Nucleic Acids Res,,,True
8263c153cb3159c41641227ad129b668e9bc2d76,PMC,The chain of communication in health science: from researcher to health worker through open access,,PMC2765774,19946398,CC BY-NC-SA,,2009 Jul 7,"['Chan, Leslie', 'Arunachalam, Subbiah', 'Kirsop, Barbara']",Open Med,,,True
95a06052b68c5712d187bd826376e31dbe8ced00,PMC,The infection of primary avian tracheal epithelial cells with infectious bronchitis virus,http://dx.doi.org/10.1051/vetres/2009054,PMC2769550,19793537,CC BY-NC,"Here we introduce a culture system for the isolation, passaging and amplification of avian tracheal epithelial (ATE) cells. The ATE medium, which contains chicken embryo extract and fetal bovine serum, supports the growth of ciliated cells, goblet cells and basal cells from chicken tracheas on fibronectin- or matrigel-coated dishes. Non-epithelial cells make up less than 10% of the total population. We further show that ATE cells support the replication and spread of infectious bronchitis virus (IBV). Interestingly, immunocytostaining revealed that basal cells are resistant to IBV infection. We also demonstrate that glycosaminoglycan had no effect on infection of the cells by IBV. Taken together, these findings suggest that primary ATE cells provide a novel cell culture system for the amplification of IBV and the in vitro characterization of viral cytopathogenesis.",2010 Oct 1 Jan-Feb,"['Shen, Ching-I', 'Wang, Ching-Ho', 'Liao, Jiunn-Wang', 'Hsu, Tien-Wang', 'Kuo, Shu-Ming', 'Su, Hong-Lin']",Vet Res,,,True
36fd2f3dfeec8932ec6e4553bce33222c4380756,PMC,Multiplex primer prediction software for divergent targets,http://dx.doi.org/10.1093/nar/gkp659,PMC2770652,19759213,CC BY-NC,"We describe a Multiplex Primer Prediction (MPP) algorithm to build multiplex compatible primer sets to amplify all members of large, diverse and unalignable sets of target sequences. The MPP algorithm is scalable to larger target sets than other available software, and it does not require a multiple sequence alignment. We applied it to questions in viral detection, and demonstrated that there are no universally conserved priming sequences among viruses and that it could require an unfeasibly large number of primers (∼3700 18-mers or ∼2000 10-mers) to generate amplicons from all sequenced viruses. We then designed primer sets separately for each viral family, and for several diverse species such as foot-and-mouth disease virus (FMDV), hemagglutinin (HA) and neuraminidase (NA) segments of influenza A virus, Norwalk virus, and HIV-1. We empirically demonstrated the application of the software with a multiplex set of 16 short (10 nt) primers designed to amplify the Poxviridae family to produce a specific amplicon from vaccinia virus.",2009 Oct 16,"['Gardner, Shea N.', 'Hiddessen, Amy L.', 'Williams, Peter L.', 'Hara, Christine', 'Wagner, Mark C.', 'Colston, Bill W.']",Nucleic Acids Res,,,True
d02f9e2414da034e0aded233a37de3077f40c93b,PMC,Short-hairpin RNAs delivered by lentiviral vector transduction trigger RIG-I-mediated IFN activation,http://dx.doi.org/10.1093/nar/gkp714,PMC2770676,19729514,CC BY-NC,"Activation of the type I interferon (IFN) pathway by small interfering RNA (siRNA) is a major contributor to the off-target effects of RNA interference in mammalian cells. While IFN induction complicates gene function studies, immunostimulation by siRNAs may be beneficial in certain therapeutic settings. Various forms of siRNA, meeting different compositional and structural requirements, have been reported to trigger IFN activation. The consensus is that intracellularly expressed short-hairpin RNAs (shRNAs) are less prone to IFN activation because they are not detected by the cell-surface receptors. In particular, lentiviral vector-mediated transduction of shRNAs has been reported to avoid IFN response. Here we identify a shRNA that potently activates the IFN pathway in human cells in a sequence- and 5′-triphosphate-dependent manner. In addition to suppressing its intended mRNA target, expression of the shRNA results in dimerization of interferon regulatory factor-3, activation of IFN promoters and secretion of biologically active IFNs into the extracellular medium. Delivery by lentiviral vector transduction did not avoid IFN activation by this and another, unrelated shRNA. We also demonstrated that retinoic-acid-inducible gene I, and not melanoma differentiation associated gene 5 or toll-like receptor 3, is the cytoplasmic sensor for intracellularly expressed shRNAs that trigger IFN activation.",2009 Oct 3,"['Kenworthy, Rachael', 'Lambert, Diana', 'Yang, Feng', 'Wang, Nan', 'Chen, Zihong', 'Zhu, Haizhen', 'Zhu, Fanxiu', 'Liu, Chen', 'Li, Kui', 'Tang, Hengli']",Nucleic Acids Res,,,True
1be90a46380a03cc53bacd389834702db88ac79b,PMC,Viral adaptation to host: a proteome-based analysis of codon usage and amino acid preferences,http://dx.doi.org/10.1038/msb.2009.71,PMC2779085,19888206,CC BY-NC-SA,"Viruses differ markedly in their specificity toward host organisms. Here, we test the level of general sequence adaptation that viruses display toward their hosts. We compiled a representative data set of viruses that infect hosts ranging from bacteria to humans. We consider their respective amino acid and codon usages and compare them among the viruses and their hosts. We show that bacteria-infecting viruses are strongly adapted to their specific hosts, but that they differ from other unrelated bacterial hosts. Viruses that infect humans, but not those that infect other mammals or aves, show a strong resemblance to most mammalian and avian hosts, in terms of both amino acid and codon preferences. In groups of viruses that infect humans or other mammals, the highest observed level of adaptation of viral proteins to host codon usages is for those proteins that appear abundantly in the virion. In contrast, proteins that are known to participate in host-specific recognition do not necessarily adapt to their respective hosts. The implication for the potential of viral infectivity is discussed.",2009 Oct 13,"['Bahir, Iris', 'Fromer, Menachem', 'Prat, Yosef', 'Linial, Michal']",Mol Syst Biol,,,True
f1b023a096d55629a623cb851f9b0a37ac678277,PMC,Viral adaptation to host: a proteome-based analysis of codon usage and amino acid preferences,http://dx.doi.org/10.1038/msb.2009.71,PMC2779085,19888206,CC BY-NC-SA,"Viruses differ markedly in their specificity toward host organisms. Here, we test the level of general sequence adaptation that viruses display toward their hosts. We compiled a representative data set of viruses that infect hosts ranging from bacteria to humans. We consider their respective amino acid and codon usages and compare them among the viruses and their hosts. We show that bacteria-infecting viruses are strongly adapted to their specific hosts, but that they differ from other unrelated bacterial hosts. Viruses that infect humans, but not those that infect other mammals or aves, show a strong resemblance to most mammalian and avian hosts, in terms of both amino acid and codon preferences. In groups of viruses that infect humans or other mammals, the highest observed level of adaptation of viral proteins to host codon usages is for those proteins that appear abundantly in the virion. In contrast, proteins that are known to participate in host-specific recognition do not necessarily adapt to their respective hosts. The implication for the potential of viral infectivity is discussed.",2009 Oct 13,"['Bahir, Iris', 'Fromer, Menachem', 'Prat, Yosef', 'Linial, Michal']",Mol Syst Biol,,,False
254c09779d5d51cd41becfb1ef4d3fcb08a0ba8f,PMC,The CEACAM1 N-terminal Ig domain mediates cis- and trans-binding and is essential for allosteric rearrangements of CEACAM1 microclusters,http://dx.doi.org/10.1083/jcb.200904149,PMC2779236,19948502,CC BY-NC-SA,"Cell adhesion molecules (CAMs) sense the extracellular microenvironment and transmit signals to the intracellular compartment. In this investigation, we addressed the mechanism of signal generation by ectodomains of single-pass transmembrane homophilic CAMs. We analyzed the structure and homophilic interactions of carcinoembryonic antigen (CEA)–related CAM 1 (CEACAM1), which regulates cell proliferation, apoptosis, motility, morphogenesis, and microbial responses. Soluble and membrane-attached CEACAM1 ectodomains were investigated by surface plasmon resonance–based biosensor analysis, molecular electron tomography, and chemical cross-linking. The CEACAM1 ectodomain, which is composed of four glycosylated immunoglobulin-like (Ig) domains, is highly flexible and participates in both antiparallel (trans) and parallel (cis) homophilic binding. Membrane-attached CEACAM1 ectodomains form microclusters in which all four Ig domains participate. Trans-binding between the N-terminal Ig domains increases formation of CEACAM1 cis-dimers and changes CEACAM1 interactions within the microclusters. These data suggest that CEACAM1 transmembrane signaling is initiated by adhesion-regulated changes of cis-interactions that are transmitted to the inner phase of the plasma membrane.",2009 Nov 16,"['Klaile, Esther', 'Vorontsova, Olga', 'Sigmundsson, Kristmundur', 'Müller, Mario M.', 'Singer, Bernhard B.', 'Öfverstedt, Lars-Göran', 'Svensson, Stina', 'Skoglund, Ulf', 'Öbrink, Björn']",J Cell Biol,,,True
0260e364e040cc9b229b2b4f727bfc2e4d68474d,PMC,Antiviral Activity of Some Plants Used in Nepalese Traditional Medicine,http://dx.doi.org/10.1093/ecam/nem156,PMC2781767,18955262,CC BY-NC,"Methanolic extracts of 41 plant species belonging to 27 families used in the traditional medicine in Nepal have been investigated for in vitro antiviral activity against Herpes simplex virus type 1 (HSV-1) and influenza virus A by dye uptake assay in the systems HSV-1/Vero cells and influenza virus A/MDCK cells. The extracts of Astilbe rivularis, Bergenia ciliata, Cassiope fastigiata and Thymus linearis showed potent anti-herpes viral activity. The extracts of Allium oreoprasum, Androsace strigilosa, Asparagus filicinus, Astilbe rivularis, Bergenia ciliata and Verbascum thapsus exhibited strong anti-influenza viral activity. Only the extracts of A. rivularis and B. ciliata demonstrated remarkable activity against both viruses.",2009 Dec 25,"['Rajbhandari, M.', 'Mentel, R.', 'Jha, P. K.', 'Chaudhary, R. P.', 'Bhattarai, S.', 'Gewali, M. B.', 'Karmacharya, N.', 'Hipper, M.', 'Lindequist, U.']",Evid Based Complement Alternat Med,,,True
9afa3940a6e7c461b7b6acfef9de23db0e420462,PMC,ORION-VIRCAT: a tool for mapping ICTV and NCBI taxonomies,http://dx.doi.org/10.1093/database/bap014,PMC2790308,20157487,CC BY-NC,"Viruses, viroids and prions are the smallest infectious biological entities that depend on their host for replication. The number of pathogenic viruses is considerably large and their impact in human global health is well documented. Currently, the International Committee on the Taxonomy of Viruses (ICTV) has classified ∼4379 virus species while the National Center for Biotechnology Information Viral Genomes Resource (NCBI-VGR) database has mapped 617 705 proteins to eight large taxonomic groups. Despite these efforts, an automated approach for mapping the ICTV master list and its officially accepted virus naming to the NCBI-VGR’s taxonomical classification is not available. Due to metagenomic sequencing, it is likely that the discovery and naming of new viral species will increase by at least ten fold. Unfortunately, existing viral databases are not adequately prepared to scale, maintain and annotate automatically ultra-high throughput sequences and place this information into specific taxonomic categories. ORION-VIRCAT is a scalable and interoperable object-relational database designed to serve as a resource for the integration and verification of taxonomical classifications generated by the ICTV and NCBI-VGR. The current release (v1.0) of ORION-VIRCAT is implemented in PostgreSQL and it has been extended to ORACLE, MySQL and SyBase. ORION-VIRCAT automatically mapped and joined 617 705 entries from the NCBI-VGR to the viral naming of the ICTV. This detailed analysis revealed that 399 095 entries from the NCBI-VGR can be mapped to the ICTV classification and that one Order, 10 families, 35 genera and 503 species listed in the ICTV disagree with the the NCBI-VGR classification schema. Nevertheless, we were eable to correct several discrepancies mapping 234 000 additional entries. Database URL: http://www.orionbiosciences.com/research/orion-vircat.html",2009 Oct 12,"['Valdivia-Granda, Willy', 'Larson, Francis']",Database (Oxford),,,True
1e2365e2734988c84a47489555f2a502edcd4cd0,PMC,A large and accurate collection of peptidase cleavages in the MEROPS database,http://dx.doi.org/10.1093/database/bap015,PMC2790309,20157488,CC BY-NC,"Peptidases are enzymes that hydrolyse peptide bonds in proteins and peptides. Peptidases are important in pathological conditions such as Alzheimer's disease, tumour and parasite invasion, and for processing viral polyproteins. The MEROPS database is an Internet resource containing information on peptidases, their substrates and inhibitors. The database now includes details of cleavage positions in substrates, both physiological and non-physiological, natural and synthetic. There are 39 118 cleavages in the collection; including 34 606 from a total of 10 513 different proteins and 2677 cleavages in synthetic substrates. The number of cleavages designated as ‘physiological’ is 13 307. The data are derived from 6095 publications. At least one substrate cleavage is known for 45% of the 2415 different peptidases recognized in the MEROPS database. The website now has three new displays: two showing peptidase specificity as a logo and a frequency matrix, the third showing a dynamically generated alignment between each protein substrate and its most closely related homologues. Many of the proteins described in the literature as peptidase substrates have been studied only in vitro. On the assumption that a physiologically relevant cleavage site would be conserved between species, the conservation of every site in terms of peptidase preference has been examined and a number have been identified that are not conserved. There are a number of cogent reasons why a site might not be conserved. Each poorly conserved site has been examined and a reason postulated. Some sites are identified that are very poorly conserved where cleavage is more likely to be fortuitous than of physiological relevance. This data-set is freely available via the Internet and is a useful training set for algorithms to predict substrates for peptidases and cleavage positions within those substrates. The data may also be useful for the design of inhibitors and for engineering novel specificities into peptidases. Database URL: http://merops.sanger.ac.uk",2009 Nov 2,"Rawlings, Neil D.",Database (Oxford),,,True
b1f4160623b02307f923593f0830bd5ef47e14ed,PMC,The United States and global health: inseparable and synergistic? The Institute of Medicine's report on global health,http://dx.doi.org/10.3402/gha.v2i0.2035,PMC2792157,20027251,CC BY-NC,"In the wake of dynamic economic and political transitions worldwide, the Institute of Medicine recently released its report advocating investments in global health from the United States (US). The expert panel reinforces the ‘transnational and interdisciplinary’ nature of global health research and practice as an endeavor ‘to improve health and achieve greater equity for all people worldwide.’ This report was judiciously timed given the growing recognition of global health, and is also acknowledged for incorporating themes that are particularly pertinent to the twenty-first century. New paradigms are introduced, denouncing the dichotomous distinction between rich and poor countries with the rapidly transitioning countries emerging as global powers, and affirming the need for models of respectful partnership and wider translation of science into practice. Cultivating sustainable partnerships and investing in the understanding and combat of diseases worldwide will become increasingly important for the US to maintain its global competitiveness, and may offer lessons in innovation, efficiency, and organization of institutions and human resources.",2009 Oct 29,"['Ali, Mohammed K.', 'Venkat Narayan, K.M.']",Glob Health Action,,,True
1d81eea0f16b71d643336838cd22e51125bf05ef,PMC,Interaction of the HIV-1 frameshift signal with the ribosome,http://dx.doi.org/10.1093/nar/gkp779,PMC2794165,19812214,CC BY-NC,"Ribosomal frameshifting on viral RNAs relies on the mechanical properties of structural elements, often pseudoknots and more rarely stem-loops, that are unfolded by the ribosome during translation. In human immunodeficiency virus (HIV)-1 type B a long hairpin containing a three-nucleotide bulge is responsible for efficient frameshifting. This three-nucleotide bulge separates the hairpin in two domains: an unstable lower stem followed by a GC-rich upper stem. Toeprinting and chemical probing assays suggest that a hairpin-like structure is retained when ribosomes, initially bound at the slippery sequence, were allowed multiple EF-G catalyzed translocation cycles. However, while the upper stem remains intact the lower stem readily melts. After the first, and single step of translocation of deacylated tRNA to the 30 S P site, movement of the mRNA stem-loop in the 5′ direction is halted, which is consistent with the notion that the downstream secondary structure resists unfolding. Mechanical stretching of the hairpin using optical tweezers only allows clear identification of unfolding of the upper stem at a force of 12.8 ± 1.0 pN. This suggests that the lower stem is unstable and may indeed readily unfold in the presence of a translocating ribosome.",2009 Dec 7,"['Mazauric, Marie-Hélène', 'Seol, Yeonee', 'Yoshizawa, Satoko', 'Visscher, Koen', 'Fourmy, Dominique']",Nucleic Acids Res,,,True
f901f9949a8c6e53727335e92a39707e89965422,PMC,The RNA polymerase activity of SARS-coronavirus nsp12 is primer dependent,http://dx.doi.org/10.1093/nar/gkp904,PMC2800238,19875418,CC BY-NC,"An RNA-dependent RNA polymerase (RdRp) is the central catalytic subunit of the RNA-synthesizing machinery of all positive-strand RNA viruses. Usually, RdRp domains are readily identifiable by comparative sequence analysis, but biochemical confirmation and characterization can be hampered by intrinsic protein properties and technical complications. It is presumed that replication and transcription of the ∼30-kb severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) RNA genome are catalyzed by an RdRp domain in the C-terminal part of nonstructural protein 12 (nsp12), one of 16 replicase subunits. However, thus far full-length nsp12 has proven refractory to expression in bacterial systems, which has hindered both the biochemical characterization of coronavirus RNA synthesis and RdRp-targeted antiviral drug design. Here, we describe a combined strategy involving bacterial expression of an nsp12 fusion protein and its in vivo cleavage to generate and purify stable SARS-CoV nsp12 (106 kDa) with a natural N-terminus and C-terminal hexahistidine tag. This recombinant protein possesses robust in vitro RdRp activity, as well as a significant DNA-dependent activity that may facilitate future inhibitor studies. The SARS-CoV nsp12 is primer dependent on both homo- and heteropolymeric templates, supporting the likeliness of a close enzymatic collaboration with the intriguing RNA primase activity that was recently proposed for coronavirus nsp8.",2010 Jan 29,"['te Velthuis, Aartjan J. W.', 'Arnold, Jamie J.', 'Cameron, Craig E.', 'van den Worm, Sjoerd H. E.', 'Snijder, Eric J.']",Nucleic Acids Res,,,True
83bb5fda8d9d959fe92af64a2f154c9dcbe38bc0,PMC,In Vitro Viability and Cytotoxicity Testing and Same-Well Multi-Parametric Combinations for High Throughput Screening,http://dx.doi.org/10.2174/1875397300903010033,PMC2802765,20161834,CC BY-NC,"In vitro cytotoxicity testing has become an integral aspect of drug discovery because it is a convenient, costeffective, and predictive means of characterizing the toxic potential of new chemical entities. The early and routine implementation of this testing is testament to its prognostic importance for humans. Although a plethora of assay chemistries and methods exist for 96-well formats, few are practical and sufficiently sensitive enough for application in high throughput screening (HTS). Here we briefly describe a handful of the currently most robust and validated HTS assays for accurate and efficient assessment of cytotoxic risk. We also provide guidance for successful HTS implementation and discuss unique merits and detractions inherent in each method. Lastly, we discuss the advantages of combining specific HTS compatible assays into multi-parametric, same-well formats.",2009 Jun 11,"['Niles, Andrew L.', 'Moravec, Richard A.', 'Riss, Terry L.']",Curr Chem Genomics,,,True
ea6c3d35646adfcd7e1c55d7d1f0998ba1107d89,PMC,Proteomics Analysis of the Nucleolus in Adenovirus-infected                         Cells,http://dx.doi.org/10.1074/mcp.M900338-MCP200,PMC2808258,19812395,CC BY-NC,"Adenoviruses replicate primarily in the host cell nucleus, and it is well established that adenovirus infection affects the structure and function of host cell nucleoli in addition to coding for a number of nucleolar targeted viral proteins. Here we used unbiased proteomics methods, including high throughput mass spectrometry coupled with stable isotope labeling by amino acids in cell culture (SILAC) and traditional two-dimensional gel electrophoresis, to identify quantitative changes in the protein composition of the nucleolus during adenovirus infection. Two-dimensional gel analysis revealed changes in six proteins. By contrast, SILAC-based approaches identified 351 proteins with 24 proteins showing at least a 2-fold change after infection. Of those, four were previously reported to have aberrant localization and/or functional relevance during adenovirus infection. In total, 15 proteins identified as changing in amount by proteomics methods were examined in infected cells using confocal microscopy. Eleven of these proteins showed altered patterns of localization in adenovirus-infected cells. Comparing our data with the effects of actinomycin D on the nucleolar proteome revealed that adenovirus infection apparently specifically targets a relatively small subset of nucleolar antigens at the time point examined.",2010 Jan 7,"['Lam, Yun W.', 'Evans, Vanessa C.', 'Heesom, Kate J.', 'Lamond, Angus I.', 'Matthews, David A.']",Mol Cell Proteomics,,,True
fef7a8f796c4068d359d7b65f03ddba1841d1738,PMC,"Recode-2: new design, new search tools, and many more genes",http://dx.doi.org/10.1093/nar/gkp788,PMC2808893,19783826,CC BY-NC,"‘Recoding’ is a term used to describe non-standard read-out of the genetic code, and encompasses such phenomena as programmed ribosomal frameshifting, stop codon readthrough, selenocysteine insertion and translational bypassing. Although only a small proportion of genes utilize recoding in protein synthesis, accurate annotation of ‘recoded’ genes lags far behind annotation of ‘standard’ genes. In order to address this issue, provide a service to researchers in the field, and offer training data for developers of gene-annotation software, we have gathered together known cases of recoding within the Recode database. Recode-2 is an improved and updated version of the database. It provides access to detailed information on genes known to utilize translational recoding and allows complex search queries, browsing of recoding data and enhanced visualization of annotated sequence elements. At present, the Recode-2 database stores information on approximately 1500 genes that are known to utilize recoding in their expression—a factor of approximately three increase over the previous version of the database. Recode-2 is available at http://recode.ucc.ie",2010 Jan 25,"['Bekaert, Michaël', 'Firth, Andrew E.', 'Zhang, Yan', 'Gladyshev, Vadim N.', 'Atkins, John F.', 'Baranov, Pavel V.']",Nucleic Acids Res,,,True
f87d2665175ce7e1c6ffd14e0da7bfc21b784e2e,PMC,ViralORFeome: an integrated database to generate a versatile collection of viral ORFs,http://dx.doi.org/10.1093/nar/gkp1000,PMC2808970,20007148,CC BY-NC,"Large collections of protein-encoding open reading frames (ORFs) established in a versatile recombination-based cloning system have been instrumental to study protein functions in high-throughput assays. Such ‘ORFeome’ resources have been developed for several organisms but in virology, plasmid collections covering a significant fraction of the virosphere are still needed. In this perspective, we present ViralORFeome 1.0 (http://www.viralorfeome.com), an open-access database and management system that provides an integrated set of bioinformatic tools to clone viral ORFs in the Gateway® system. ViralORFeome provides a convenient interface to navigate through virus genome sequences, to design ORF-specific cloning primers, to validate the sequence of generated constructs and to browse established collections of virus ORFs. Most importantly, ViralORFeome has been designed to manage all possible variants or mutants of a given ORF so that the cloning procedure can be applied to any emerging virus strain. A subset of plasmid constructs generated with ViralORFeome platform has been tested with success for heterologous protein expression in different expression systems at proteome scale. ViralORFeome should provide our community with a framework to establish a large collection of virus ORF clones, an instrumental resource to determine functions, activities and binding partners of viral proteins.",2010 Jan 8,"['Pellet, J.', 'Tafforeau, L.', 'Lucas-Hourani, M.', 'Navratil, V.', 'Meyniel, L.', 'Achaz, G.', 'Guironnet-Paquet, A.', 'Aublin-Gex, A.', 'Caignard, G.', 'Cassonnet, P.', 'Chaboud, A.', 'Chantier, T.', 'Deloire, A.', 'Demeret, C.', 'Le Breton, M.', 'Neveu, G.', 'Jacotot, L.', 'Vaglio, P.', 'Delmotte, S.', 'Gautier, C.', 'Combet, C.', 'Deleage, G.', 'Favre, M.', 'Tangy, F.', 'Jacob, Y.', 'Andre, P.', 'Lotteau, V.', 'Rabourdin-Combe, C.', 'Vidalain, P. O.']",Nucleic Acids Res,,,True
67db14be4e5b68f4d42496330429a1d86266a161,PMC,Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model,http://dx.doi.org/10.1051/vetres/2009076,PMC2821766,20003910,CC BY-NC,"Beginning in 2003, highly pathogenic avian influenza (HPAI) H5N1 virus spread across Southeast Asia, causing unprecedented epidemics. Thailand was massively infected in 2004 and 2005 and continues today to experience sporadic outbreaks. While research findings suggest that the spread of HPAI H5N1 is influenced primarily by trade patterns, identifying the anthropogenic risk factors involved remains a challenge. In this study, we investigated which anthropogenic factors played a role in the risk of HPAI in Thailand using outbreak data from the “second wave” of the epidemic (3 July 2004 to 5 May 2005) in the country. We first performed a spatial analysis of the relative risk of HPAI H5N1 at the subdistrict level based on a hierarchical Bayesian model. We observed a strong spatial heterogeneity of the relative risk. We then tested a set of potential risk factors in a multivariable linear model. The results confirmed the role of free-grazing ducks and rice-cropping intensity but showed a weak association with fighting cock density. The results also revealed a set of anthropogenic factors significantly linked with the risk of HPAI. High risk was associated strongly with densely populated areas, short distances to a highway junction, and short distances to large cities. These findings highlight a new explanatory pattern for the risk of HPAI and indicate that, in addition to agro-environmental factors, anthropogenic factors play an important role in the spread of H5N1. To limit the spread of future outbreaks, efforts to control the movement of poultry products must be sustained.",2010 Dec 16 May-Jun,"['Paul, Mathilde', 'Tavornpanich, Saraya', 'Abrial, David', 'Gasqui, Patrick', 'Charras-Garrido, Myriam', 'Thanapongtharm, Weerapong', 'Xiao, Xiangming', 'Gilbert, Marius', 'Roger, Francois', 'Ducrot, Christian']",Vet Res,,,True
801e028d1c0aa75910dbe03019538ed0dc28b905,PMC,Attenuated Salmonella choleraesuis-mediated RNAi targeted to conserved regions against foot-and-mouth disease virus in guinea pigs and swine,http://dx.doi.org/10.1051/vetres/2010002,PMC2826090,20167192,CC BY-NC,"In this study, specific sequences within three genes (3D, VP4 and 2B) of the foot-and-mouth disease virus (FMDV) genome were determined to be effective RNAi targets. These sequences are highly conserved among different serotype viruses based on sequence analysis. Small interfering RNA (siRNA)-expressing plasmids (p3D-NT19, p3D-NT56, pVP4-NT19, pVP4-NT65 and p2B-NT25) were constructed to express siRNA targeting 3D, VP4 and 2B, respectively. The antiviral potential of these siRNA for various FMDV isolates was investigated in baby hamster kidney (BHK-21) cells and suckling mice. The results show that these siRNA inhibited virus yield 10- to 300-fold for different FMDV isolates of serotype O and serotype Asia I at 48 h post infection in BHK-21 cells compared to control cells. In suckling mice, p3D-NT56 and p2B-NT25 delayed the death of mice. Twenty percent to 40% of the animals that received a single siRNA dose survived 5 days post infection with serotype O or serotype Asia I. We used an attenuated Salmonella choleraesuis (C500) vaccine strain, to carry the plasmid that expresses siRNA directed against the polymerase gene 3D (p3D-NT56) of FMDV. We used guinea pigs to evaluate the inhibitory effects of recombinant S. cho (p3D-NT56/S. cho) on FMDV infection. The results show that 80% of guinea pigs inoculated with 10(9) CFU of p3D-NT56/S. cho and challenged 36 h later with 50 ID(50) of homologous FMDV were protected. We also measured the antiviral activity of p3D-NT56/S. cho in swine. The results indicate that 100% of the animals treated with 5 × 10(9) CFU of p3D-NT56/S. cho were protected in 9 days.",2010 Jan 13 May-Jun,"['Cong, Wei', 'Jin, Hong', 'Jiang, Chengda', 'Yan, Weiyao', 'Liu, Mingqiu', 'Chen, Jiulian', 'Zuo, Xiaoping', 'Zheng, Zhaoxin']",Vet Res,,,True
105b993dee9f9e44637daa2d43e66f3ba3039fbf,PMC,Mechanisms of viral emergence,http://dx.doi.org/10.1051/vetres/2010010,PMC2831534,20167200,CC BY-NC,"A number of virologic and environmental factors are involved in the emergence and re-emergence of viral disease. Viruses do not conservatively occupy a single and permanent ecological niche. Rather, due to their intrinsic capacity for genetic change, and to the evolvability of fitness levels, viruses display a potential to parasitize alternative host species. Mutation, recombination and genome segment reassortment, and combination of these molecular events, produce complex and phenotypically diverse populations of viruses, which constitute the raw material on which selection acts. The majority of emerging viral diseases of humans have a zoonotic origin. Sociologic and ecologic factors produce diverse and changing environments in which viral subpopulations have ample opportunities to be selected from intrinsically heterogeneous viral populations, particularly in the case of RNA viruses. In this manner, new human, animal and plant viruses have emerged periodically and, from all evidence, will continue to emerge. This article reviews some of the mechanisms that have been identified in viral emergence, with a focus on the importance of genetic variation of viruses, and on the general concept of biological complexity.",2010 Feb 5 Nov-Dec,"Domingo, Esteban",Vet Res,,,True
f59470fcae185cd02092b4e6e986a558ab811e92,PMC,An intermolecular RNA triplex provides insight into structural determinants for the pseudoknot stimulator of −1 ribosomal frameshifting,http://dx.doi.org/10.1093/nar/gkp1107,PMC2836554,20007152,CC BY-NC,"An efficient −1 programmed ribosomal frameshifting (PRF) signal requires an RNA slippery sequence and a downstream RNA stimulator, and the hairpin-type pseudoknot is the most common stimulator. However, a pseudoknot is not sufficient to promote −1 PRF. hTPK-DU177, a pseudoknot derived from human telomerase RNA, shares structural similarities with several −1 PRF pseudoknots and is used to dissect the roles of distinct structural features in the stimulator of −1 PRF. Structure-based mutagenesis on hTPK-DU177 reveals that the −1 PRF efficiency of this stimulator can be modulated by sequential removal of base–triple interactions surrounding the helical junction. Further analysis of the junction-flanking base triples indicates that specific stem–loop interactions and their relative positions to the helical junction play crucial roles for the −1 PRF activity of this pseudoknot. Intriguingly, a bimolecular pseudoknot approach based on hTPK-DU177 reveals that continuing triplex structure spanning the helical junction, lacking one of the loop-closure features embedded in pseudoknot topology, can stimulate −1 PRF. Therefore, the triplex structure is an essential determinant for the DU177 pseudoknot to stimulate −1 PRF. Furthermore, it suggests that −1 PRF, induced by an in-trans RNA via specific base–triple interactions with messenger RNAs, can be a plausible regulatory function for non-coding RNAs.",2010 Mar 8,"['Chou, Ming-Yuan', 'Chang, Kung-Yao']",Nucleic Acids Res,,,True
15e262dad93d5086e9fcb6a1267dec5189f5c1fe,PMC,The UNITAID Patent Pool Initiative: Bringing Patents Together for the Common Good,http://dx.doi.org/10.2174/1874613601004020037,PMC2842943,20309404,CC BY-NC,"Developing and delivering appropriate, affordable, well-adapted medicines for HIV/AIDS remains an urgent challenge: as first-line therapies fail, increasing numbers of people require costly second-line therapy; one-third of ARVs are not available in pediatric formulations; and certain key first- and second-line triple fixed-dose combinations do not exist or sufficient suppliers are lacking. UNITAID aims to help solve these problems through an innovative initiative for the collective management of intellectual property (IP) rights – a patent pool for HIV medicines. The idea behind a patent pool is that patent holders - companies, governments, researchers or universities - voluntarily offer, under certain conditions, the IP related to their inventions to the patent pool. Any company that wants to use the IP to produce or develop medicines can seek a license from the pool against the payment of royalties, and may then produce the medicines for use in developing countries (conditional upon meeting agreed quality standards). The patent pool will be a voluntary mechanism, meaning its success will largely depend on the willingness of pharmaceutical companies to participate and commit their IP to the pool. Generic producers must also be willing to cooperate. The pool has the potential to provide benefits to all.",2010 Jan 19,"['Bermudez, Jorge', ""'t Hoen, Ellen""]",Open AIDS J,,,True
4a79e0975e99b65456d69c3310e842402202e64e,PMC,DotKnot: pseudoknot prediction using the probability dot plot under a refined energy model,http://dx.doi.org/10.1093/nar/gkq021,PMC2853144,20123730,CC BY-NC,"RNA pseudoknots are functional structure elements with key roles in viral and cellular processes. Prediction of a pseudoknotted minimum free energy structure is an NP-complete problem. Practical algorithms for RNA structure prediction including restricted classes of pseudoknots suffer from high runtime and poor accuracy for longer sequences. A heuristic approach is to search for promising pseudoknot candidates in a sequence and verify those. Afterwards, the detected pseudoknots can be further analysed using bioinformatics or laboratory techniques. We present a novel pseudoknot detection method called DotKnot that extracts stem regions from the secondary structure probability dot plot and assembles pseudoknot candidates in a constructive fashion. We evaluate pseudoknot free energies using novel parameters, which have recently become available. We show that the conventional probability dot plot makes a wide class of pseudoknots including those with bulged stems manageable in an explicit fashion. The energy parameters now become the limiting factor in pseudoknot prediction. DotKnot is an efficient method for long sequences, which finds pseudoknots with higher accuracy compared to other known prediction algorithms. DotKnot is accessible as a web server at http://dotknot.csse.uwa.edu.au.",2010 Apr 31,"['Sperschneider, Jana', 'Datta, Amitava']",Nucleic Acids Res,,,False
62f47ced8c3249f702f0058dc3b6cdb93ca083eb,PMC,DotKnot: pseudoknot prediction using the probability dot plot under a refined energy model,http://dx.doi.org/10.1093/nar/gkq021,PMC2853144,20123730,CC BY-NC,"RNA pseudoknots are functional structure elements with key roles in viral and cellular processes. Prediction of a pseudoknotted minimum free energy structure is an NP-complete problem. Practical algorithms for RNA structure prediction including restricted classes of pseudoknots suffer from high runtime and poor accuracy for longer sequences. A heuristic approach is to search for promising pseudoknot candidates in a sequence and verify those. Afterwards, the detected pseudoknots can be further analysed using bioinformatics or laboratory techniques. We present a novel pseudoknot detection method called DotKnot that extracts stem regions from the secondary structure probability dot plot and assembles pseudoknot candidates in a constructive fashion. We evaluate pseudoknot free energies using novel parameters, which have recently become available. We show that the conventional probability dot plot makes a wide class of pseudoknots including those with bulged stems manageable in an explicit fashion. The energy parameters now become the limiting factor in pseudoknot prediction. DotKnot is an efficient method for long sequences, which finds pseudoknots with higher accuracy compared to other known prediction algorithms. DotKnot is accessible as a web server at http://dotknot.csse.uwa.edu.au.",2010 Apr 31,"['Sperschneider, Jana', 'Datta, Amitava']",Nucleic Acids Res,,,True
54ba95ea3a5c0f2d84d225438c3935de1167056e,PMC,Cloning whole bacterial genomes in yeast,http://dx.doi.org/10.1093/nar/gkq119,PMC2860123,20211840,CC BY-NC,"Most microbes have not been cultured, and many of those that are cultivatable are difficult, dangerous or expensive to propagate or are genetically intractable. Routine cloning of large genome fractions or whole genomes from these organisms would significantly enhance their discovery and genetic and functional characterization. Here we report the cloning of whole bacterial genomes in the yeast Saccharomyces cerevisiae as single-DNA molecules. We cloned the genomes of Mycoplasma genitalium (0.6 Mb), M. pneumoniae (0.8 Mb) and M. mycoides subspecies capri (1.1 Mb) as yeast circular centromeric plasmids. These genomes appear to be stably maintained in a host that has efficient, well-established methods for DNA manipulation.",2010 May 7,"['Benders, Gwynedd A.', 'Noskov, Vladimir N.', 'Denisova, Evgeniya A.', 'Lartigue, Carole', 'Gibson, Daniel G.', 'Assad-Garcia, Nacyra', 'Chuang, Ray-Yuan', 'Carrera, William', 'Moodie, Monzia', 'Algire, Mikkel A.', 'Phan, Quang', 'Alperovich, Nina', 'Vashee, Sanjay', 'Merryman, Chuck', 'Venter, J. Craig', 'Smith, Hamilton O.', 'Glass, John I.', 'Hutchison, Clyde A.']",Nucleic Acids Res,,,False
c147fd685f974994cea6cb2329084754f655062c,PMC,Cloning whole bacterial genomes in yeast,http://dx.doi.org/10.1093/nar/gkq119,PMC2860123,20211840,CC BY-NC,"Most microbes have not been cultured, and many of those that are cultivatable are difficult, dangerous or expensive to propagate or are genetically intractable. Routine cloning of large genome fractions or whole genomes from these organisms would significantly enhance their discovery and genetic and functional characterization. Here we report the cloning of whole bacterial genomes in the yeast Saccharomyces cerevisiae as single-DNA molecules. We cloned the genomes of Mycoplasma genitalium (0.6 Mb), M. pneumoniae (0.8 Mb) and M. mycoides subspecies capri (1.1 Mb) as yeast circular centromeric plasmids. These genomes appear to be stably maintained in a host that has efficient, well-established methods for DNA manipulation.",2010 May 7,"['Benders, Gwynedd A.', 'Noskov, Vladimir N.', 'Denisova, Evgeniya A.', 'Lartigue, Carole', 'Gibson, Daniel G.', 'Assad-Garcia, Nacyra', 'Chuang, Ray-Yuan', 'Carrera, William', 'Moodie, Monzia', 'Algire, Mikkel A.', 'Phan, Quang', 'Alperovich, Nina', 'Vashee, Sanjay', 'Merryman, Chuck', 'Venter, J. Craig', 'Smith, Hamilton O.', 'Glass, John I.', 'Hutchison, Clyde A.']",Nucleic Acids Res,,,True
8a6809df45d5f80a822d68d3c305f7640e10234a,PMC,Large-scale evolutionary surveillance of the 2009 H1N1 influenza A virus using resequencing arrays,http://dx.doi.org/10.1093/nar/gkq089,PMC2874996,20185568,CC BY-NC,"In April 2009, a new influenza A (H1N1 2009) virus emerged that rapidly spread around the world. While current variants of this virus have caused widespread disease, particularly in vulnerable groups, there remains the possibility that future variants may cause increased virulence, drug resistance or vaccine escape. Early detection of these virus variants may offer the chance for increased containment and potentially prevention of the virus spread. We have developed and field-tested a resequencing kit that is capable of interrogating all eight segments of the 2009 influenza A(H1N1) virus genome and its variants, with added focus on critical regions such as drug-binding sites, structural components and mutation hotspots. The accompanying base-calling software (EvolSTAR) introduces novel methods that utilize neighbourhood hybridization intensity profiles and substitution bias of probes on the microarray for mutation confirmation and recovery of ambiguous base queries. Our results demonstrate that EvolSTAR is highly accurate and has a much improved call rate. The high throughput and short turn-around time from sample to sequence and analysis results (30 h for 24 samples) makes this kit an efficient large-scale evolutionary biosurveillance tool.",2010 May 25,"['Lee, Charlie Wah Heng', 'Koh, Chee Wee', 'Chan, Yang Sun', 'Aw, Pauline Poh Kim', 'Loh, Kuan Hon', 'Han, Bing Ling', 'Thien, Pei Ling', 'Nai, Geraldine Yi Wen', 'Hibberd, Martin L.', 'Wong, Christopher W.', 'Sung, Wing-Kin']",Nucleic Acids Res,,,True
93dae518889d2a93960963fa3e99158f58738eda,PMC,A Novel Construction of Genome Space with Biological Geometry,http://dx.doi.org/10.1093/dnares/dsq008,PMC2885272,20360268,CC BY-NC,"A genome space is a moduli space of genomes. In this space, each point corresponds to a genome. The natural distance between two points in the genome space reflects the biological distance between these two genomes. Currently, there is no method to represent genomes by a point in a space without losing biological information. Here, we propose a new graphical representation for DNA sequences. The breakthrough of the subject is that we can construct the moment vectors from DNA sequences using this new graphical method and prove that the correspondence between moment vectors and DNA sequences is one-to-one. Using these moment vectors, we have constructed a novel genome space as a subspace in R(N). It allows us to show that the SARS-CoV is most closely related to a coronavirus from the palm civet not from a bird as initially suspected, and the newly discovered human coronavirus HCoV-HKU1 is more closely related to SARS than to any other known member of group 2 coronavirus. Furthermore, we reconstructed the phylogenetic tree for 34 lentiviruses (including human immunodeficiency virus) based on their whole genome sequences. Our genome space will provide a new powerful tool for analyzing the classification of genomes and their phylogenetic relationships.",2010 Jun 1,"['Yu, Chenglong', 'Liang, Qian', 'Yin, Changchuan', 'He, Rong L.', 'Yau, Stephen S.-T.']",DNA Res,,,True
41e98d93f0f9f490c34dc4e8f96340cf477e7355,PMC,Radiological and Clinical Characteristics of a Military Outbreak of Pandemic H1N1 2009 Influenza Virus Infection,http://dx.doi.org/10.3348/kjr.2010.11.4.417,PMC2893312,20592925,CC BY-NC,"OBJECTIVE: To describe detailed clinical and radiological features of the pandemic H1N1 2009 influenza viral infection among healthy young males in a semi-closed institutionalized setting. MATERIALS AND METHODS: A total of 18 patients confirmed with the pandemic H1N1 2009 influenza virus infection from July 18 to July 30, 2009 were enrolled in this study. Each patient underwent an evaluation to determine detailed clinical and radiological features. RESULTS: All patients presented with high fever (> 38.0℃), with accompanying symptoms of cough, rhinorrhea, sore throat, myalgia and diarrhea, and increased C-reactive protein (CRP) values with no leukocytosis nor elevated erythrocyte sedimentation rate (ESR). All patients, including one patient who progressed into acute respiratory distress syndrome, were treated with oseltamivir phosphate and quickly recovered from their symptoms. Chest radiographs showed abnormalities of small nodules and lobar consolidation in only two out of 18 patients. However, six of 12 patients who underwent thin-section CT examinations showed abnormal findings for small ground-glass opacities (GGOs) in addition to poorly-defined nodules with upper lobe predominance. CONCLUSION: In a population of healthy young adults, elevated CRP with normal ESR and white blood cell levels combined with GGOs and nodules on thin-section CT scans may indicate early signs of infection by the pandemic H1N1 2009 influenza virus.",2010 Jun 21 Jul-Aug,"['Yun, Tae Jin', 'Kwon, Gu Jin', 'Oh, Mi Kyeong', 'Woo, Sung Koo', 'Park, Seung Hoon', 'Choi, Seung Hong', 'Lee, Hyun Ju', 'Goo, Jin Mo', 'Yim, Jae-Joon', 'Kim, Jong Sung', 'Park, Chang Min']",Korean J Radiol,,,True
3e40cb7055fe5ef148eced8994ff059a0e98aef1,PMC,i-GSEA4GWAS: a web server for identification of pathways/gene sets associated with traits by applying an improved gene set enrichment analysis to genome-wide association study,http://dx.doi.org/10.1093/nar/gkq324,PMC2896119,20435672,CC BY-NC,"Genome-wide association study (GWAS) is nowadays widely used to identify genes involved in human complex disease. The standard GWAS analysis examines SNPs/genes independently and identifies only a number of the most significant SNPs. It ignores the combined effect of weaker SNPs/genes, which leads to difficulties to explore biological function and mechanism from a systems point of view. Although gene set enrichment analysis (GSEA) has been introduced to GWAS to overcome these limitations by identifying the correlation between pathways/gene sets and traits, the heavy dependence on genotype data, which is not easily available for most published GWAS investigations, has led to limited application of it. In order to perform GSEA on a simple list of GWAS SNP P-values, we implemented GSEA by using SNP label permutation. We further improved GSEA (i-GSEA) by focusing on pathways/gene sets with high proportion of significant genes. To provide researchers an open platform to analyze GWAS data, we developed the i-GSEA4GWAS (improved GSEA for GWAS) web server. i-GSEA4GWAS implements the i-GSEA approach and aims to provide new insights in complex disease studies. i-GSEA4GWAS is freely available at http://gsea4gwas.psych.ac.cn/.",2010 Jul 1,"['Zhang, Kunlin', 'Cui, Sijia', 'Chang, Suhua', 'Zhang, Liuyan', 'Wang, Jing']",Nucleic Acids Res,,,True
67629939944591734aa3934d4a2c9aadf49ccedf,PMC,Global Health and Foreign Policy,http://dx.doi.org/10.1093/epirev/mxq006,PMC2898916,20423936,CC BY-NC,"Health has long been intertwined with the foreign policies of states. In recent years, however, global health issues have risen to the highest levels of international politics and have become accepted as legitimate issues in foreign policy. This elevated political priority is in many ways a welcome development for proponents of global health, and it has resulted in increased funding for and attention to select global health issues. However, there has been less examination of the tensions that characterize the relationship between global health and foreign policy and of the potential effects of linking global health efforts with the foreign-policy interests of states. In this paper, the authors review the relationship between global health and foreign policy by examining the roles of health across 4 major components of foreign policy: aid, trade, diplomacy, and national security. For each of these aspects of foreign policy, the authors review current and historical issues and discuss how foreign-policy interests have aided or impeded global health efforts. The increasing relevance of global health to foreign policy holds both opportunities and dangers for global efforts to improve health.",2010 Apr 27,"['Feldbaum, Harley', 'Lee, Kelley', 'Michaud, Joshua']",Epidemiol Rev,,,True
735b7fb564d6661cc009df5fe3245244aaa745eb,PMC,Elastase-mediated Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein at Discrete Sites within the S2 Domain,http://dx.doi.org/10.1074/jbc.M110.103275,PMC2906266,20507992,CC BY-NC,"Proteolytic priming is a common method of controlling the activation of membrane fusion mediated by viral glycoproteins. The severe acute respiratory syndrome coronavirus spike protein (SARS-CoV S) can be primed by a variety of host cell proteases, with proteolytic cleavage occurring both as the S1/S2 boundary and adjacent to a fusion peptide in the S2 domain. Here, we studied the priming of SARS-CoV S by elastase and show an important role for residue Thr(795) in the S2 domain. A series of alanine mutants were generated in the vicinity of the S2 cleavage site, with the goal of examining elastase-mediated cleavage within S2. Both proteolytic cleavage and fusion activation were modulated by altering the cleavage site position. We propose a novel mechanism whereby SARS-CoV fusion protein function can be controlled by spatial regulation of the proteolytic priming site, with important implications for viral pathogenesis.",2010 Jul 23,"['Belouzard, Sandrine', 'Madu, Ikenna', 'Whittaker, Gary R.']",J Biol Chem,,,False
a9a1447dbe61ed4271eea3a74fb4e0bb7b340653,PMC,Elastase-mediated Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein at Discrete Sites within the S2 Domain,http://dx.doi.org/10.1074/jbc.M110.103275,PMC2906266,20507992,CC BY-NC,"Proteolytic priming is a common method of controlling the activation of membrane fusion mediated by viral glycoproteins. The severe acute respiratory syndrome coronavirus spike protein (SARS-CoV S) can be primed by a variety of host cell proteases, with proteolytic cleavage occurring both as the S1/S2 boundary and adjacent to a fusion peptide in the S2 domain. Here, we studied the priming of SARS-CoV S by elastase and show an important role for residue Thr(795) in the S2 domain. A series of alanine mutants were generated in the vicinity of the S2 cleavage site, with the goal of examining elastase-mediated cleavage within S2. Both proteolytic cleavage and fusion activation were modulated by altering the cleavage site position. We propose a novel mechanism whereby SARS-CoV fusion protein function can be controlled by spatial regulation of the proteolytic priming site, with important implications for viral pathogenesis.",2010 Jul 23,"['Belouzard, Sandrine', 'Madu, Ikenna', 'Whittaker, Gary R.']",J Biol Chem,,,False
e9768f172dbcdb024e83fe12728b889ea0c3fdec,PMC,Elastase-mediated Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein at Discrete Sites within the S2 Domain,http://dx.doi.org/10.1074/jbc.M110.103275,PMC2906266,20507992,CC BY-NC,"Proteolytic priming is a common method of controlling the activation of membrane fusion mediated by viral glycoproteins. The severe acute respiratory syndrome coronavirus spike protein (SARS-CoV S) can be primed by a variety of host cell proteases, with proteolytic cleavage occurring both as the S1/S2 boundary and adjacent to a fusion peptide in the S2 domain. Here, we studied the priming of SARS-CoV S by elastase and show an important role for residue Thr(795) in the S2 domain. A series of alanine mutants were generated in the vicinity of the S2 cleavage site, with the goal of examining elastase-mediated cleavage within S2. Both proteolytic cleavage and fusion activation were modulated by altering the cleavage site position. We propose a novel mechanism whereby SARS-CoV fusion protein function can be controlled by spatial regulation of the proteolytic priming site, with important implications for viral pathogenesis.",2010 Jul 23,"['Belouzard, Sandrine', 'Madu, Ikenna', 'Whittaker, Gary R.']",J Biol Chem,,,False
a9e9e47667e6630156203fe938e7afb876583934,PMC,Elastase-mediated Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein at Discrete Sites within the S2 Domain,http://dx.doi.org/10.1074/jbc.M110.103275,PMC2906266,20507992,CC BY-NC,"Proteolytic priming is a common method of controlling the activation of membrane fusion mediated by viral glycoproteins. The severe acute respiratory syndrome coronavirus spike protein (SARS-CoV S) can be primed by a variety of host cell proteases, with proteolytic cleavage occurring both as the S1/S2 boundary and adjacent to a fusion peptide in the S2 domain. Here, we studied the priming of SARS-CoV S by elastase and show an important role for residue Thr(795) in the S2 domain. A series of alanine mutants were generated in the vicinity of the S2 cleavage site, with the goal of examining elastase-mediated cleavage within S2. Both proteolytic cleavage and fusion activation were modulated by altering the cleavage site position. We propose a novel mechanism whereby SARS-CoV fusion protein function can be controlled by spatial regulation of the proteolytic priming site, with important implications for viral pathogenesis.",2010 Jul 23,"['Belouzard, Sandrine', 'Madu, Ikenna', 'Whittaker, Gary R.']",J Biol Chem,,,True
d92992c5c544e78fdc31b8d52a1aa14c84ef0807,PMC,"Identification of Adenovirus, Influenza Virus, Parainfluenza Virus, and Respiratory Syncytial Virus by Two Kinds of Multiplex Polymerase Chain Reaction (PCR) and a Shell Vial Culture in Pediatric Patients with Viral Pneumonia",http://dx.doi.org/10.3349/ymj.2010.51.5.761,PMC2908874,20635453,CC BY-NC,"PURPOSE: Early identification of causative agents in lower respiratory infection of pediatric patients can reduce morbidity and prevent an overuse of antimicrobials. Two kinds of multiplex polymerase chain reaction (PCR) and a commercial shell vial viral culture were performed to identify causative agents in pediatric patients. MATERIALS AND METHODS: Nasopharyngeal aspirates of 220 children diagnosed with viral pneumonia were obtained. Two kinds of multiplex PCR (Seeplex™ RV detection kit, and Labopass™ RV detection kit), and a shell vial culture by R-Mix were performed. RESULTS: Positive samples from 220 total samples by two multiplex PCRs were 52.7% and 46.4%, respectively. We also cultured 103 samples that showed positive results of the adenovirus, influenza virus, parainfluenza virus, and respiratory syncytial virus (RSV) by two multiplex PCR. The RSV was most frequently detected in 53.0% (Seeplex) and 51.7% (Labopass) of patients. The detection rate of adenovirus (AdV) was 10.3% and 12.1%, influenza virus (IFV) A and B was 12.5% and 3.4%, and parainfluenza virus (PIFV) 1, 2, and 3 were 2.9% and 2.6%. Shell vial cultures showed concordant results with each multiplex PCR by 96.1% and 77.7%, respectively. Sequencing results were 90% consistent with multiplex PCR. CONCLUSION: Multiplex PCR showed more positivity than the shell vial culture and it can be an effective primary test. Other complementary efforts such as viral cultures and sequencing analysis could be considered, according to clinical and laboratory conditions.",2010 Sep 1,"['Lee, Jong-Han', 'Chun, Jin-Kyong', 'Kim, Dong Soo', 'Park, Yongjung', 'Choi, Jong Rak', 'Kim, Hyon-Suk']",Yonsei Med J,,,True
ff5a79ed22ea416e6d89caad1cf0d83dbc741a4b,PMC,Understanding Human Coronavirus HCoV-NL63,http://dx.doi.org/10.2174/1874357901004010076,PMC2918871,20700397,CC BY-NC,"Even though coronavirus infection of humans is not normally associated with severe diseases, the identification of the coronavirus responsible for the outbreak of severe acute respiratory syndrome showed that highly pathogenic coronaviruses can enter the human population. Shortly thereafter, in Holland in 2004, another novel human coronavirus (HCoV-NL63) was isolated from a seven-month old infant suffering from respiratory symptoms. This virus has subsequently been identified in various countries, indicating a worldwide distribution. HCoV-NL63 has been shown to infect mainly children and the immunocommpromised, who presented with either mild upper respiratory symptoms (cough, fever and rhinorrhoea) or more serious lower respiratory tract involvement such as bronchiolitis and croup, which was observed mainly in younger children. In fact, HCoV-NL63 is the aetiological agent for up to 10% of all respiratory diseases. This review summarizes recent findings of human coronavirus HCoV-NL63 infections, including isolation and identification, phylogeny and taxonomy, genome structure and transcriptional regulation, transmission and pathogenesis, and detection and diagnosis.",2010 May 25,"['Abdul-Rasool, Sahar', 'Fielding, Burtram C']",Open Virol J,,,True
1876b56402bb5f33b4c0469501896fe5fed2e36e,PMC,Association of bacteria and viruses with wheezy episodes in young children: prospective birth cohort study,http://dx.doi.org/10.1136/bmj.c4978,PMC2950260,20921080,CC BY-NC,"Objective To study the association between wheezy symptoms in young children and the presence of bacteria in the airways. Design Birth cohort study. Setting Clinical research unit in Copenhagen. Participants Children of asthmatic mothers, from age 4 weeks to 3 years, with planned visits and acute admissions to the research clinic. Main outcome measure Frequency of bacteria and virus carriage in airway aspirates during wheezy episodes and at planned visits without respiratory symptoms. Results 984 samples (361 children) were analysed for bacteria, 844 (299 children) for viruses, and 696 (277 children) for both viruses and bacteria. Wheezy episodes were associated with both bacterial infection (odds ratio 2.9, 95% confidence interval 1.9 to 4.3; P<0.001) and virus infection (2.8, 1.7 to 4.4; P<0.001). The associations of bacteria and viruses were independent of each other. Conclusion Acute wheezy episodes in young children were significantly associated with bacterial infections similar to but independent of the association with virus infections.",2010 Oct 4,"['Bisgaard, Hans', 'Hermansen, Mette Northman', 'Bønnelykke, Klaus', 'Stokholm, Jakob', 'Baty, Florent', 'Skytt, Nanna Lassen', 'Aniscenko, Julia', 'Kebadze, Tatiana', 'Johnston, Sebastian L']",BMJ,,,False
85bf5d9dc1c35cdf7db6d95309a91a37d4bc5b08,PMC,Association of bacteria and viruses with wheezy episodes in young children: prospective birth cohort study,http://dx.doi.org/10.1136/bmj.c4978,PMC2950260,20921080,CC BY-NC,"Objective To study the association between wheezy symptoms in young children and the presence of bacteria in the airways. Design Birth cohort study. Setting Clinical research unit in Copenhagen. Participants Children of asthmatic mothers, from age 4 weeks to 3 years, with planned visits and acute admissions to the research clinic. Main outcome measure Frequency of bacteria and virus carriage in airway aspirates during wheezy episodes and at planned visits without respiratory symptoms. Results 984 samples (361 children) were analysed for bacteria, 844 (299 children) for viruses, and 696 (277 children) for both viruses and bacteria. Wheezy episodes were associated with both bacterial infection (odds ratio 2.9, 95% confidence interval 1.9 to 4.3; P<0.001) and virus infection (2.8, 1.7 to 4.4; P<0.001). The associations of bacteria and viruses were independent of each other. Conclusion Acute wheezy episodes in young children were significantly associated with bacterial infections similar to but independent of the association with virus infections.",2010 Oct 4,"['Bisgaard, Hans', 'Hermansen, Mette Northman', 'Bønnelykke, Klaus', 'Stokholm, Jakob', 'Baty, Florent', 'Skytt, Nanna Lassen', 'Aniscenko, Julia', 'Kebadze, Tatiana', 'Johnston, Sebastian L']",BMJ,,,False
8dee8cdd7ec3e279aa74444855d117bc381adb62,PMC,Association of bacteria and viruses with wheezy episodes in young children: prospective birth cohort study,http://dx.doi.org/10.1136/bmj.c4978,PMC2950260,20921080,CC BY-NC,"Objective To study the association between wheezy symptoms in young children and the presence of bacteria in the airways. Design Birth cohort study. Setting Clinical research unit in Copenhagen. Participants Children of asthmatic mothers, from age 4 weeks to 3 years, with planned visits and acute admissions to the research clinic. Main outcome measure Frequency of bacteria and virus carriage in airway aspirates during wheezy episodes and at planned visits without respiratory symptoms. Results 984 samples (361 children) were analysed for bacteria, 844 (299 children) for viruses, and 696 (277 children) for both viruses and bacteria. Wheezy episodes were associated with both bacterial infection (odds ratio 2.9, 95% confidence interval 1.9 to 4.3; P<0.001) and virus infection (2.8, 1.7 to 4.4; P<0.001). The associations of bacteria and viruses were independent of each other. Conclusion Acute wheezy episodes in young children were significantly associated with bacterial infections similar to but independent of the association with virus infections.",2010 Oct 4,"['Bisgaard, Hans', 'Hermansen, Mette Northman', 'Bønnelykke, Klaus', 'Stokholm, Jakob', 'Baty, Florent', 'Skytt, Nanna Lassen', 'Aniscenko, Julia', 'Kebadze, Tatiana', 'Johnston, Sebastian L']",BMJ,,,False
dd0863296aa29156993cde032a4f7f42f5133fff,PMC,Autocrine Interferon Priming in Macrophages but Not Dendritic Cells Results in Enhanced Cytokine and Chemokine Production after Coronavirus Infection,http://dx.doi.org/10.1128/mBio.00219-10,PMC2957079,20978536,CC BY-NC-SA,"Coronaviruses efficiently inhibit interferon (IFN) induction in nonhematopoietic cells and conventional dendritic cells (cDC). However, IFN is produced in infected macrophages, microglia, and plasmacytoid dendritic cells (pDC). To begin to understand why IFN is produced in infected macrophages, we infected bone marrow-derived macrophages (BMM) and as a control, bone marrow-derived DC (BMDC) with the coronavirus mouse hepatitis virus (MHV). As expected, BMM but not BMDC expressed type I IFN. IFN production in infected BMM was nearly completely dependent on signaling through the alpha/beta interferon (IFN-α/β) receptor (IFNAR). Several IFN-dependent cytokines and chemokines showed the same expression pattern, with enhanced production in BMM compared to BMDC and dependence upon signaling through the IFNAR. Exogenous IFN enhanced IFN-dependent gene expression in BMM at early times after infection and in BMDC at all times after infection but did not stimulate expression of molecules that signal through myeloid differentiation factor 88 (MyD88), such as tumor necrosis factor (TNF). Collectively, our results show that IFN is produced at early times postinfection (p.i.) in MHV-infected BMM, but not in BMDC, and primes expression of IFN and IFN-responsive genes. Further, our results also show that BMM are generally more responsive to MHV infection, since MyD88-dependent pathways are also activated to a greater extent in these cells than in BMDC.",2010 Oct 19,"['Zhou, Haixia', 'Zhao, Jincun', 'Perlman, Stanley']",mBio,,,True
3c3ab717ef79befde82029b1362348708998d17e,PMC,Unique Signatures of Long Noncoding RNA Expression in Response to Virus Infection and Altered Innate Immune Signaling,http://dx.doi.org/10.1128/mBio.00206-10,PMC2962437,20978541,CC BY-NC-SA,"Studies of the host response to virus infection typically focus on protein-coding genes. However, non-protein-coding RNAs (ncRNAs) are transcribed in mammalian cells, and the roles of many of these ncRNAs remain enigmas. Using next-generation sequencing, we performed a whole-transcriptome analysis of the host response to severe acute respiratory syndrome coronavirus (SARS-CoV) infection across four founder mouse strains of the Collaborative Cross. We observed differential expression of approximately 500 annotated, long ncRNAs and 1,000 nonannotated genomic regions during infection. Moreover, studies of a subset of these ncRNAs and genomic regions showed the following. (i) Most were similarly regulated in response to influenza virus infection. (ii) They had distinctive kinetic expression profiles in type I interferon receptor and STAT1 knockout mice during SARS-CoV infection, including unique signatures of ncRNA expression associated with lethal infection. (iii) Over 40% were similarly regulated in vitro in response to both influenza virus infection and interferon treatment. These findings represent the first discovery of the widespread differential expression of long ncRNAs in response to virus infection and suggest that ncRNAs are involved in regulating the host response, including innate immunity. At the same time, virus infection models provide a unique platform for studying the biology and regulation of ncRNAs.",2010 Oct 26,"['Peng, Xinxia', 'Gralinski, Lisa', 'Armour, Christopher D.', 'Ferris, Martin T.', 'Thomas, Matthew J.', 'Proll, Sean', 'Bradel-Tretheway, Birgit G.', 'Korth, Marcus J.', 'Castle, John C.', 'Biery, Matthew C.', 'Bouzek, Heather K.', 'Haynor, David R.', 'Frieman, Matthew B.', 'Heise, Mark', 'Raymond, Christopher K.', 'Baric, Ralph S.', 'Katze, Michael G.']",mBio,,,True
6d1041fcc03030731eb70d3fcd72f421f9f461bd,PMC,Unique Signatures of Long Noncoding RNA Expression in Response to Virus Infection and Altered Innate Immune Signaling,http://dx.doi.org/10.1128/mBio.00206-10,PMC2962437,20978541,CC BY-NC-SA,"Studies of the host response to virus infection typically focus on protein-coding genes. However, non-protein-coding RNAs (ncRNAs) are transcribed in mammalian cells, and the roles of many of these ncRNAs remain enigmas. Using next-generation sequencing, we performed a whole-transcriptome analysis of the host response to severe acute respiratory syndrome coronavirus (SARS-CoV) infection across four founder mouse strains of the Collaborative Cross. We observed differential expression of approximately 500 annotated, long ncRNAs and 1,000 nonannotated genomic regions during infection. Moreover, studies of a subset of these ncRNAs and genomic regions showed the following. (i) Most were similarly regulated in response to influenza virus infection. (ii) They had distinctive kinetic expression profiles in type I interferon receptor and STAT1 knockout mice during SARS-CoV infection, including unique signatures of ncRNA expression associated with lethal infection. (iii) Over 40% were similarly regulated in vitro in response to both influenza virus infection and interferon treatment. These findings represent the first discovery of the widespread differential expression of long ncRNAs in response to virus infection and suggest that ncRNAs are involved in regulating the host response, including innate immunity. At the same time, virus infection models provide a unique platform for studying the biology and regulation of ncRNAs.",2010 Oct 26,"['Peng, Xinxia', 'Gralinski, Lisa', 'Armour, Christopher D.', 'Ferris, Martin T.', 'Thomas, Matthew J.', 'Proll, Sean', 'Bradel-Tretheway, Birgit G.', 'Korth, Marcus J.', 'Castle, John C.', 'Biery, Matthew C.', 'Bouzek, Heather K.', 'Haynor, David R.', 'Frieman, Matthew B.', 'Heise, Mark', 'Raymond, Christopher K.', 'Baric, Ralph S.', 'Katze, Michael G.']",mBio,,,False
fdb9a8be66fff92e838be9ce72e28b0cafc60366,PMC,Unique Signatures of Long Noncoding RNA Expression in Response to Virus Infection and Altered Innate Immune Signaling,http://dx.doi.org/10.1128/mBio.00206-10,PMC2962437,20978541,CC BY-NC-SA,"Studies of the host response to virus infection typically focus on protein-coding genes. However, non-protein-coding RNAs (ncRNAs) are transcribed in mammalian cells, and the roles of many of these ncRNAs remain enigmas. Using next-generation sequencing, we performed a whole-transcriptome analysis of the host response to severe acute respiratory syndrome coronavirus (SARS-CoV) infection across four founder mouse strains of the Collaborative Cross. We observed differential expression of approximately 500 annotated, long ncRNAs and 1,000 nonannotated genomic regions during infection. Moreover, studies of a subset of these ncRNAs and genomic regions showed the following. (i) Most were similarly regulated in response to influenza virus infection. (ii) They had distinctive kinetic expression profiles in type I interferon receptor and STAT1 knockout mice during SARS-CoV infection, including unique signatures of ncRNA expression associated with lethal infection. (iii) Over 40% were similarly regulated in vitro in response to both influenza virus infection and interferon treatment. These findings represent the first discovery of the widespread differential expression of long ncRNAs in response to virus infection and suggest that ncRNAs are involved in regulating the host response, including innate immunity. At the same time, virus infection models provide a unique platform for studying the biology and regulation of ncRNAs.",2010 Oct 26,"['Peng, Xinxia', 'Gralinski, Lisa', 'Armour, Christopher D.', 'Ferris, Martin T.', 'Thomas, Matthew J.', 'Proll, Sean', 'Bradel-Tretheway, Birgit G.', 'Korth, Marcus J.', 'Castle, John C.', 'Biery, Matthew C.', 'Bouzek, Heather K.', 'Haynor, David R.', 'Frieman, Matthew B.', 'Heise, Mark', 'Raymond, Christopher K.', 'Baric, Ralph S.', 'Katze, Michael G.']",mBio,,,False
9835beda27f1dd6f88639b7047079c9e509afcdd,PMC,Unique Signatures of Long Noncoding RNA Expression in Response to Virus Infection and Altered Innate Immune Signaling,http://dx.doi.org/10.1128/mBio.00206-10,PMC2962437,20978541,CC BY-NC-SA,"Studies of the host response to virus infection typically focus on protein-coding genes. However, non-protein-coding RNAs (ncRNAs) are transcribed in mammalian cells, and the roles of many of these ncRNAs remain enigmas. Using next-generation sequencing, we performed a whole-transcriptome analysis of the host response to severe acute respiratory syndrome coronavirus (SARS-CoV) infection across four founder mouse strains of the Collaborative Cross. We observed differential expression of approximately 500 annotated, long ncRNAs and 1,000 nonannotated genomic regions during infection. Moreover, studies of a subset of these ncRNAs and genomic regions showed the following. (i) Most were similarly regulated in response to influenza virus infection. (ii) They had distinctive kinetic expression profiles in type I interferon receptor and STAT1 knockout mice during SARS-CoV infection, including unique signatures of ncRNA expression associated with lethal infection. (iii) Over 40% were similarly regulated in vitro in response to both influenza virus infection and interferon treatment. These findings represent the first discovery of the widespread differential expression of long ncRNAs in response to virus infection and suggest that ncRNAs are involved in regulating the host response, including innate immunity. At the same time, virus infection models provide a unique platform for studying the biology and regulation of ncRNAs.",2010 Oct 26,"['Peng, Xinxia', 'Gralinski, Lisa', 'Armour, Christopher D.', 'Ferris, Martin T.', 'Thomas, Matthew J.', 'Proll, Sean', 'Bradel-Tretheway, Birgit G.', 'Korth, Marcus J.', 'Castle, John C.', 'Biery, Matthew C.', 'Bouzek, Heather K.', 'Haynor, David R.', 'Frieman, Matthew B.', 'Heise, Mark', 'Raymond, Christopher K.', 'Baric, Ralph S.', 'Katze, Michael G.']",mBio,,,False
76a35dec1787d836ec94e6243a01d6898386df1a,PMC,Unique Signatures of Long Noncoding RNA Expression in Response to Virus Infection and Altered Innate Immune Signaling,http://dx.doi.org/10.1128/mBio.00206-10,PMC2962437,20978541,CC BY-NC-SA,"Studies of the host response to virus infection typically focus on protein-coding genes. However, non-protein-coding RNAs (ncRNAs) are transcribed in mammalian cells, and the roles of many of these ncRNAs remain enigmas. Using next-generation sequencing, we performed a whole-transcriptome analysis of the host response to severe acute respiratory syndrome coronavirus (SARS-CoV) infection across four founder mouse strains of the Collaborative Cross. We observed differential expression of approximately 500 annotated, long ncRNAs and 1,000 nonannotated genomic regions during infection. Moreover, studies of a subset of these ncRNAs and genomic regions showed the following. (i) Most were similarly regulated in response to influenza virus infection. (ii) They had distinctive kinetic expression profiles in type I interferon receptor and STAT1 knockout mice during SARS-CoV infection, including unique signatures of ncRNA expression associated with lethal infection. (iii) Over 40% were similarly regulated in vitro in response to both influenza virus infection and interferon treatment. These findings represent the first discovery of the widespread differential expression of long ncRNAs in response to virus infection and suggest that ncRNAs are involved in regulating the host response, including innate immunity. At the same time, virus infection models provide a unique platform for studying the biology and regulation of ncRNAs.",2010 Oct 26,"['Peng, Xinxia', 'Gralinski, Lisa', 'Armour, Christopher D.', 'Ferris, Martin T.', 'Thomas, Matthew J.', 'Proll, Sean', 'Bradel-Tretheway, Birgit G.', 'Korth, Marcus J.', 'Castle, John C.', 'Biery, Matthew C.', 'Bouzek, Heather K.', 'Haynor, David R.', 'Frieman, Matthew B.', 'Heise, Mark', 'Raymond, Christopher K.', 'Baric, Ralph S.', 'Katze, Michael G.']",mBio,,,False
9a6d14471d9c34da1c4f1bf4ef530a35f58ad863,PMC,Alternative splicing of CD200 is regulated by an exonic splicing enhancer and SF2/ASF,http://dx.doi.org/10.1093/nar/gkq554,PMC2965252,20558599,CC BY-NC,"CD200, a type I membrane glycoprotein, plays an important role in prevention of inflammatory disorders, graft rejection, autoimmune diseases and spontaneous fetal loss. It also regulates tumor immunity. A truncated CD200 (CD200(tr)) resulting from alternative splicing has been identified and characterized as a functional antagonist to full-length CD200. Thus, it is important to explore the mechanism(s) controlling alternative splicing of CD200. In this study, we identified an exonic splicing enhancer (ESE) located in exon 2, which is a putative binding site for a splicing regulatory protein SF2/ASF. Deletion or mutation of the ESE site decreased expression of the full-length CD200. Direct binding of SF2/ASF to the ESE site was confirmed by RNA electrophoretic mobility shift assay (EMSA). Knockdown of expression of SF2/ASF resulted in the same splicing pattern as seen after deletion or mutation of the ESE, whereas overexpression of SF2/ASF increased expression of the full-length CD200. In vivo studies showed that viral infection reversed the alternative splicing pattern of CD200 with increased expression of SF2/ASF and the full-length CD200. Taken together, our data suggest for the first time that SF2/ASF regulates the function of CD200 by controlling CD200 alternative splicing, through direct binding to an ESE located in exon 2 of CD200.",2010 Oct 17,"['Chen, Zhiqi', 'Ma, Xuezhong', 'Zhang, Jianhua', 'Hu, Jim', 'Gorczynski, Reginald M.']",Nucleic Acids Res,,,True
3606dd5863dea1e8d6b7d7480ffb9baa06305382,PMC,Alternative splicing of CD200 is regulated by an exonic splicing enhancer and SF2/ASF,http://dx.doi.org/10.1093/nar/gkq554,PMC2965252,20558599,CC BY-NC,"CD200, a type I membrane glycoprotein, plays an important role in prevention of inflammatory disorders, graft rejection, autoimmune diseases and spontaneous fetal loss. It also regulates tumor immunity. A truncated CD200 (CD200(tr)) resulting from alternative splicing has been identified and characterized as a functional antagonist to full-length CD200. Thus, it is important to explore the mechanism(s) controlling alternative splicing of CD200. In this study, we identified an exonic splicing enhancer (ESE) located in exon 2, which is a putative binding site for a splicing regulatory protein SF2/ASF. Deletion or mutation of the ESE site decreased expression of the full-length CD200. Direct binding of SF2/ASF to the ESE site was confirmed by RNA electrophoretic mobility shift assay (EMSA). Knockdown of expression of SF2/ASF resulted in the same splicing pattern as seen after deletion or mutation of the ESE, whereas overexpression of SF2/ASF increased expression of the full-length CD200. In vivo studies showed that viral infection reversed the alternative splicing pattern of CD200 with increased expression of SF2/ASF and the full-length CD200. Taken together, our data suggest for the first time that SF2/ASF regulates the function of CD200 by controlling CD200 alternative splicing, through direct binding to an ESE located in exon 2 of CD200.",2010 Oct 17,"['Chen, Zhiqi', 'Ma, Xuezhong', 'Zhang, Jianhua', 'Hu, Jim', 'Gorczynski, Reginald M.']",Nucleic Acids Res,,,False
b8f3cb6fd720c0f2150816c37362174e61a1ca22,PMC,Identification of a Severe Acute Respiratory Syndrome Coronavirus-Like Virus in a Leaf-Nosed Bat in Nigeria,http://dx.doi.org/10.1128/mBio.00208-10,PMC2975989,21063474,CC BY-NC-SA,"Bats are reservoirs for emerging zoonotic viruses that can have a profound impact on human and animal health, including lyssaviruses, filoviruses, paramyxoviruses, and severe acute respiratory syndrome coronaviruses (SARS-CoVs). In the course of a project focused on pathogen discovery in contexts where human-bat contact might facilitate more efficient interspecies transmission of viruses, we surveyed gastrointestinal tissue obtained from bats collected in caves in Nigeria that are frequented by humans. Coronavirus consensus PCR and unbiased high-throughput pyrosequencing revealed the presence of coronavirus sequences related to those of SARS-CoV in a Commerson’s leaf-nosed bat (Hipposideros commersoni). Additional genomic sequencing indicated that this virus, unlike subgroup 2b CoVs, which includes SARS-CoV, is unique, comprising three overlapping open reading frames between the M and N genes and two conserved stem-loop II motifs. Phylogenetic analyses in conjunction with these features suggest that this virus represents a new subgroup within group 2 CoVs.",2010 Oct 12,"['Quan, Phenix-Lan', 'Firth, Cadhla', 'Street, Craig', 'Henriquez, Jose A.', 'Petrosov, Alexandra', 'Tashmukhamedova, Alla', 'Hutchison, Stephen K.', 'Egholm, Michael', 'Osinubi, Modupe O. V.', 'Niezgoda, Michael', 'Ogunkoya, Albert B.', 'Briese, Thomas', 'Rupprecht, Charles E.', 'Lipkin, W. Ian']",mBio,,,True
1ad72ce8b3e71e2ef006d944fe1b01223e3f8e3b,PMC,Identification of a Severe Acute Respiratory Syndrome Coronavirus-Like Virus in a Leaf-Nosed Bat in Nigeria,http://dx.doi.org/10.1128/mBio.00208-10,PMC2975989,21063474,CC BY-NC-SA,"Bats are reservoirs for emerging zoonotic viruses that can have a profound impact on human and animal health, including lyssaviruses, filoviruses, paramyxoviruses, and severe acute respiratory syndrome coronaviruses (SARS-CoVs). In the course of a project focused on pathogen discovery in contexts where human-bat contact might facilitate more efficient interspecies transmission of viruses, we surveyed gastrointestinal tissue obtained from bats collected in caves in Nigeria that are frequented by humans. Coronavirus consensus PCR and unbiased high-throughput pyrosequencing revealed the presence of coronavirus sequences related to those of SARS-CoV in a Commerson’s leaf-nosed bat (Hipposideros commersoni). Additional genomic sequencing indicated that this virus, unlike subgroup 2b CoVs, which includes SARS-CoV, is unique, comprising three overlapping open reading frames between the M and N genes and two conserved stem-loop II motifs. Phylogenetic analyses in conjunction with these features suggest that this virus represents a new subgroup within group 2 CoVs.",2010 Oct 12,"['Quan, Phenix-Lan', 'Firth, Cadhla', 'Street, Craig', 'Henriquez, Jose A.', 'Petrosov, Alexandra', 'Tashmukhamedova, Alla', 'Hutchison, Stephen K.', 'Egholm, Michael', 'Osinubi, Modupe O. V.', 'Niezgoda, Michael', 'Ogunkoya, Albert B.', 'Briese, Thomas', 'Rupprecht, Charles E.', 'Lipkin, W. Ian']",mBio,,,False
1dd1685b3ca8acf4e2ddbf62cbde88bb11e2afab,PMC,Identification of a Severe Acute Respiratory Syndrome Coronavirus-Like Virus in a Leaf-Nosed Bat in Nigeria,http://dx.doi.org/10.1128/mBio.00208-10,PMC2975989,21063474,CC BY-NC-SA,"Bats are reservoirs for emerging zoonotic viruses that can have a profound impact on human and animal health, including lyssaviruses, filoviruses, paramyxoviruses, and severe acute respiratory syndrome coronaviruses (SARS-CoVs). In the course of a project focused on pathogen discovery in contexts where human-bat contact might facilitate more efficient interspecies transmission of viruses, we surveyed gastrointestinal tissue obtained from bats collected in caves in Nigeria that are frequented by humans. Coronavirus consensus PCR and unbiased high-throughput pyrosequencing revealed the presence of coronavirus sequences related to those of SARS-CoV in a Commerson’s leaf-nosed bat (Hipposideros commersoni). Additional genomic sequencing indicated that this virus, unlike subgroup 2b CoVs, which includes SARS-CoV, is unique, comprising three overlapping open reading frames between the M and N genes and two conserved stem-loop II motifs. Phylogenetic analyses in conjunction with these features suggest that this virus represents a new subgroup within group 2 CoVs.",2010 Oct 12,"['Quan, Phenix-Lan', 'Firth, Cadhla', 'Street, Craig', 'Henriquez, Jose A.', 'Petrosov, Alexandra', 'Tashmukhamedova, Alla', 'Hutchison, Stephen K.', 'Egholm, Michael', 'Osinubi, Modupe O. V.', 'Niezgoda, Michael', 'Ogunkoya, Albert B.', 'Briese, Thomas', 'Rupprecht, Charles E.', 'Lipkin, W. Ian']",mBio,,,False
5f4cca82a9cbf23b9e0088a81966c3c9ae2c3f20,PMC,Identification of a Severe Acute Respiratory Syndrome Coronavirus-Like Virus in a Leaf-Nosed Bat in Nigeria,http://dx.doi.org/10.1128/mBio.00208-10,PMC2975989,21063474,CC BY-NC-SA,"Bats are reservoirs for emerging zoonotic viruses that can have a profound impact on human and animal health, including lyssaviruses, filoviruses, paramyxoviruses, and severe acute respiratory syndrome coronaviruses (SARS-CoVs). In the course of a project focused on pathogen discovery in contexts where human-bat contact might facilitate more efficient interspecies transmission of viruses, we surveyed gastrointestinal tissue obtained from bats collected in caves in Nigeria that are frequented by humans. Coronavirus consensus PCR and unbiased high-throughput pyrosequencing revealed the presence of coronavirus sequences related to those of SARS-CoV in a Commerson’s leaf-nosed bat (Hipposideros commersoni). Additional genomic sequencing indicated that this virus, unlike subgroup 2b CoVs, which includes SARS-CoV, is unique, comprising three overlapping open reading frames between the M and N genes and two conserved stem-loop II motifs. Phylogenetic analyses in conjunction with these features suggest that this virus represents a new subgroup within group 2 CoVs.",2010 Oct 12,"['Quan, Phenix-Lan', 'Firth, Cadhla', 'Street, Craig', 'Henriquez, Jose A.', 'Petrosov, Alexandra', 'Tashmukhamedova, Alla', 'Hutchison, Stephen K.', 'Egholm, Michael', 'Osinubi, Modupe O. V.', 'Niezgoda, Michael', 'Ogunkoya, Albert B.', 'Briese, Thomas', 'Rupprecht, Charles E.', 'Lipkin, W. Ian']",mBio,,,False
fa3d312d96b3eb8ed53b8e1ebf3d6f1025863c76,PMC,Identification of a Severe Acute Respiratory Syndrome Coronavirus-Like Virus in a Leaf-Nosed Bat in Nigeria,http://dx.doi.org/10.1128/mBio.00208-10,PMC2975989,21063474,CC BY-NC-SA,"Bats are reservoirs for emerging zoonotic viruses that can have a profound impact on human and animal health, including lyssaviruses, filoviruses, paramyxoviruses, and severe acute respiratory syndrome coronaviruses (SARS-CoVs). In the course of a project focused on pathogen discovery in contexts where human-bat contact might facilitate more efficient interspecies transmission of viruses, we surveyed gastrointestinal tissue obtained from bats collected in caves in Nigeria that are frequented by humans. Coronavirus consensus PCR and unbiased high-throughput pyrosequencing revealed the presence of coronavirus sequences related to those of SARS-CoV in a Commerson’s leaf-nosed bat (Hipposideros commersoni). Additional genomic sequencing indicated that this virus, unlike subgroup 2b CoVs, which includes SARS-CoV, is unique, comprising three overlapping open reading frames between the M and N genes and two conserved stem-loop II motifs. Phylogenetic analyses in conjunction with these features suggest that this virus represents a new subgroup within group 2 CoVs.",2010 Oct 12,"['Quan, Phenix-Lan', 'Firth, Cadhla', 'Street, Craig', 'Henriquez, Jose A.', 'Petrosov, Alexandra', 'Tashmukhamedova, Alla', 'Hutchison, Stephen K.', 'Egholm, Michael', 'Osinubi, Modupe O. V.', 'Niezgoda, Michael', 'Ogunkoya, Albert B.', 'Briese, Thomas', 'Rupprecht, Charles E.', 'Lipkin, W. Ian']",mBio,,,False
cf65b82be2947a66b9b1d425a8a674f1795ed884,PMC,Identification of a Severe Acute Respiratory Syndrome Coronavirus-Like Virus in a Leaf-Nosed Bat in Nigeria,http://dx.doi.org/10.1128/mBio.00208-10,PMC2975989,21063474,CC BY-NC-SA,"Bats are reservoirs for emerging zoonotic viruses that can have a profound impact on human and animal health, including lyssaviruses, filoviruses, paramyxoviruses, and severe acute respiratory syndrome coronaviruses (SARS-CoVs). In the course of a project focused on pathogen discovery in contexts where human-bat contact might facilitate more efficient interspecies transmission of viruses, we surveyed gastrointestinal tissue obtained from bats collected in caves in Nigeria that are frequented by humans. Coronavirus consensus PCR and unbiased high-throughput pyrosequencing revealed the presence of coronavirus sequences related to those of SARS-CoV in a Commerson’s leaf-nosed bat (Hipposideros commersoni). Additional genomic sequencing indicated that this virus, unlike subgroup 2b CoVs, which includes SARS-CoV, is unique, comprising three overlapping open reading frames between the M and N genes and two conserved stem-loop II motifs. Phylogenetic analyses in conjunction with these features suggest that this virus represents a new subgroup within group 2 CoVs.",2010 Oct 12,"['Quan, Phenix-Lan', 'Firth, Cadhla', 'Street, Craig', 'Henriquez, Jose A.', 'Petrosov, Alexandra', 'Tashmukhamedova, Alla', 'Hutchison, Stephen K.', 'Egholm, Michael', 'Osinubi, Modupe O. V.', 'Niezgoda, Michael', 'Ogunkoya, Albert B.', 'Briese, Thomas', 'Rupprecht, Charles E.', 'Lipkin, W. Ian']",mBio,,,False
382a81107832e8994225a4f37c73be4cd26e1c43,PMC,Identification of a Severe Acute Respiratory Syndrome Coronavirus-Like Virus in a Leaf-Nosed Bat in Nigeria,http://dx.doi.org/10.1128/mBio.00208-10,PMC2975989,21063474,CC BY-NC-SA,"Bats are reservoirs for emerging zoonotic viruses that can have a profound impact on human and animal health, including lyssaviruses, filoviruses, paramyxoviruses, and severe acute respiratory syndrome coronaviruses (SARS-CoVs). In the course of a project focused on pathogen discovery in contexts where human-bat contact might facilitate more efficient interspecies transmission of viruses, we surveyed gastrointestinal tissue obtained from bats collected in caves in Nigeria that are frequented by humans. Coronavirus consensus PCR and unbiased high-throughput pyrosequencing revealed the presence of coronavirus sequences related to those of SARS-CoV in a Commerson’s leaf-nosed bat (Hipposideros commersoni). Additional genomic sequencing indicated that this virus, unlike subgroup 2b CoVs, which includes SARS-CoV, is unique, comprising three overlapping open reading frames between the M and N genes and two conserved stem-loop II motifs. Phylogenetic analyses in conjunction with these features suggest that this virus represents a new subgroup within group 2 CoVs.",2010 Oct 12,"['Quan, Phenix-Lan', 'Firth, Cadhla', 'Street, Craig', 'Henriquez, Jose A.', 'Petrosov, Alexandra', 'Tashmukhamedova, Alla', 'Hutchison, Stephen K.', 'Egholm, Michael', 'Osinubi, Modupe O. V.', 'Niezgoda, Michael', 'Ogunkoya, Albert B.', 'Briese, Thomas', 'Rupprecht, Charles E.', 'Lipkin, W. Ian']",mBio,,,False
8166f11427e1a0dbfde68dbcbb59dd52c907e780,PMC,The SARS Coronavirus E Protein Interacts with PALS1 and Alters Tight Junction Formation and Epithelial Morphogenesis,http://dx.doi.org/10.1091/mbc.E10-04-0338,PMC2982091,20861307,CC BY-NC-SA,"Intercellular tight junctions define epithelial apicobasal polarity and form a physical fence which protects underlying tissues from pathogen invasions. PALS1, a tight junction-associated protein, is a member of the CRUMBS3-PALS1-PATJ polarity complex, which is crucial for the establishment and maintenance of epithelial polarity in mammals. Here we report that the carboxy-terminal domain of the SARS-CoV E small envelope protein (E) binds to human PALS1. Using coimmunoprecipitation and pull-down assays, we show that E interacts with PALS1 in mammalian cells and further demonstrate that the last four carboxy-terminal amino acids of E form a novel PDZ-binding motif that binds to PALS1 PDZ domain. PALS1 redistributes to the ERGIC/Golgi region, where E accumulates, in SARS-CoV–infected Vero E6 cells. Ectopic expression of E in MDCKII epithelial cells significantly alters cyst morphogenesis and, furthermore, delays formation of tight junctions, affects polarity, and modifies the subcellular distribution of PALS1, in a PDZ-binding motif-dependent manner. We speculate that hijacking of PALS1 by SARS-CoV E plays a determinant role in the disruption of the lung epithelium in SARS patients.",2010 Nov 15,"['Teoh, Kim-Tat', 'Siu, Yu-Lam', 'Chan, Wing-Lim', 'Schlüter, Marc A.', 'Liu, Chia-Jen', 'Peiris, J. S. Malik', 'Bruzzone, Roberto', 'Margolis, Benjamin', 'Nal, Béatrice']",Mol Biol Cell,,,False
315e05b0b70437ddf56976d8890cc347b89cbfde,PMC,Quantitative Proteomic Analysis of A549 Cells Infected with Human Respiratory Syncytial Virus,http://dx.doi.org/10.1074/mcp.M110.001859,PMC2984239,20647383,CC BY-NC,"Human respiratory syncytial virus (HRSV) is a major cause of pediatric lower respiratory tract disease to which there is no vaccine or efficacious chemotherapeutic strategy. Although RNA synthesis and virus assembly occur in the cytoplasm, HRSV is known to induce nuclear responses in the host cell as replication alters global gene expression. Quantitative proteomics was used to take an unbiased overview of the protein changes in transformed human alveolar basal epithelial cells infected with HRSV. Underpinning this was the use of stable isotope labeling with amino acids in cell culture coupled to LC-MS/MS, which allowed the direct and simultaneous identification and quantification of both cellular and viral proteins. To reduce sample complexity and increase data return on potential protein localization, cells were fractionated into nuclear and cytoplasmic extracts. This resulted in the identification of 1,140 cellular proteins and six viral proteins. The proteomics data were analyzed using Ingenuity Pathways Analysis to identify defined canonical pathways and functional groupings. Selected data were validated using Western blot, direct and indirect immunofluorescence confocal microscopy, and functional assays. The study served to validate and expand upon known HRSV-host cell interactions, including those associated with the antiviral response and alterations in subnuclear structures such as the nucleolus and ND10 (promyelocytic leukemia bodies). In addition, novel changes were observed in mitochondrial proteins and functions, cell cycle regulatory molecules, nuclear pore complex proteins and nucleocytoplasmic trafficking proteins. These data shed light into how the cell is potentially altered to create conditions more favorable for infection. Additionally, the study highlights the application and advantage of stable isotope labeling with amino acids in cell culture coupled to LC-MS/MS for the analysis of virus-host interactions.",2010 Nov 20,"['Munday, Diane C.', 'Emmott, Edward', 'Surtees, Rebecca', 'Lardeau, Charles-Hugues', 'Wu, Weining', 'Duprex, W. Paul', 'Dove, Brian K.', 'Barr, John N.', 'Hiscox, Julian A.']",Mol Cell Proteomics,,,False
a395411b3c22ecb1b3baf2fb058e734bc07f2623,PMC,Quantitative Proteomic Analysis of A549 Cells Infected with Human Respiratory Syncytial Virus,http://dx.doi.org/10.1074/mcp.M110.001859,PMC2984239,20647383,CC BY-NC,"Human respiratory syncytial virus (HRSV) is a major cause of pediatric lower respiratory tract disease to which there is no vaccine or efficacious chemotherapeutic strategy. Although RNA synthesis and virus assembly occur in the cytoplasm, HRSV is known to induce nuclear responses in the host cell as replication alters global gene expression. Quantitative proteomics was used to take an unbiased overview of the protein changes in transformed human alveolar basal epithelial cells infected with HRSV. Underpinning this was the use of stable isotope labeling with amino acids in cell culture coupled to LC-MS/MS, which allowed the direct and simultaneous identification and quantification of both cellular and viral proteins. To reduce sample complexity and increase data return on potential protein localization, cells were fractionated into nuclear and cytoplasmic extracts. This resulted in the identification of 1,140 cellular proteins and six viral proteins. The proteomics data were analyzed using Ingenuity Pathways Analysis to identify defined canonical pathways and functional groupings. Selected data were validated using Western blot, direct and indirect immunofluorescence confocal microscopy, and functional assays. The study served to validate and expand upon known HRSV-host cell interactions, including those associated with the antiviral response and alterations in subnuclear structures such as the nucleolus and ND10 (promyelocytic leukemia bodies). In addition, novel changes were observed in mitochondrial proteins and functions, cell cycle regulatory molecules, nuclear pore complex proteins and nucleocytoplasmic trafficking proteins. These data shed light into how the cell is potentially altered to create conditions more favorable for infection. Additionally, the study highlights the application and advantage of stable isotope labeling with amino acids in cell culture coupled to LC-MS/MS for the analysis of virus-host interactions.",2010 Nov 20,"['Munday, Diane C.', 'Emmott, Edward', 'Surtees, Rebecca', 'Lardeau, Charles-Hugues', 'Wu, Weining', 'Duprex, W. Paul', 'Dove, Brian K.', 'Barr, John N.', 'Hiscox, Julian A.']",Mol Cell Proteomics,,,False
281204abdffa235230ba49a8f1bb3dfc3e283fcc,PMC,Quantitative Proteomic Analysis of A549 Cells Infected with Human Respiratory Syncytial Virus,http://dx.doi.org/10.1074/mcp.M110.001859,PMC2984239,20647383,CC BY-NC,"Human respiratory syncytial virus (HRSV) is a major cause of pediatric lower respiratory tract disease to which there is no vaccine or efficacious chemotherapeutic strategy. Although RNA synthesis and virus assembly occur in the cytoplasm, HRSV is known to induce nuclear responses in the host cell as replication alters global gene expression. Quantitative proteomics was used to take an unbiased overview of the protein changes in transformed human alveolar basal epithelial cells infected with HRSV. Underpinning this was the use of stable isotope labeling with amino acids in cell culture coupled to LC-MS/MS, which allowed the direct and simultaneous identification and quantification of both cellular and viral proteins. To reduce sample complexity and increase data return on potential protein localization, cells were fractionated into nuclear and cytoplasmic extracts. This resulted in the identification of 1,140 cellular proteins and six viral proteins. The proteomics data were analyzed using Ingenuity Pathways Analysis to identify defined canonical pathways and functional groupings. Selected data were validated using Western blot, direct and indirect immunofluorescence confocal microscopy, and functional assays. The study served to validate and expand upon known HRSV-host cell interactions, including those associated with the antiviral response and alterations in subnuclear structures such as the nucleolus and ND10 (promyelocytic leukemia bodies). In addition, novel changes were observed in mitochondrial proteins and functions, cell cycle regulatory molecules, nuclear pore complex proteins and nucleocytoplasmic trafficking proteins. These data shed light into how the cell is potentially altered to create conditions more favorable for infection. Additionally, the study highlights the application and advantage of stable isotope labeling with amino acids in cell culture coupled to LC-MS/MS for the analysis of virus-host interactions.",2010 Nov 20,"['Munday, Diane C.', 'Emmott, Edward', 'Surtees, Rebecca', 'Lardeau, Charles-Hugues', 'Wu, Weining', 'Duprex, W. Paul', 'Dove, Brian K.', 'Barr, John N.', 'Hiscox, Julian A.']",Mol Cell Proteomics,,,False
054831a6a11886b5ad44cac71d17e367721a2b5b,PMC,Quantitative Proteomic Analysis of A549 Cells Infected with Human Respiratory Syncytial Virus,http://dx.doi.org/10.1074/mcp.M110.001859,PMC2984239,20647383,CC BY-NC,"Human respiratory syncytial virus (HRSV) is a major cause of pediatric lower respiratory tract disease to which there is no vaccine or efficacious chemotherapeutic strategy. Although RNA synthesis and virus assembly occur in the cytoplasm, HRSV is known to induce nuclear responses in the host cell as replication alters global gene expression. Quantitative proteomics was used to take an unbiased overview of the protein changes in transformed human alveolar basal epithelial cells infected with HRSV. Underpinning this was the use of stable isotope labeling with amino acids in cell culture coupled to LC-MS/MS, which allowed the direct and simultaneous identification and quantification of both cellular and viral proteins. To reduce sample complexity and increase data return on potential protein localization, cells were fractionated into nuclear and cytoplasmic extracts. This resulted in the identification of 1,140 cellular proteins and six viral proteins. The proteomics data were analyzed using Ingenuity Pathways Analysis to identify defined canonical pathways and functional groupings. Selected data were validated using Western blot, direct and indirect immunofluorescence confocal microscopy, and functional assays. The study served to validate and expand upon known HRSV-host cell interactions, including those associated with the antiviral response and alterations in subnuclear structures such as the nucleolus and ND10 (promyelocytic leukemia bodies). In addition, novel changes were observed in mitochondrial proteins and functions, cell cycle regulatory molecules, nuclear pore complex proteins and nucleocytoplasmic trafficking proteins. These data shed light into how the cell is potentially altered to create conditions more favorable for infection. Additionally, the study highlights the application and advantage of stable isotope labeling with amino acids in cell culture coupled to LC-MS/MS for the analysis of virus-host interactions.",2010 Nov 20,"['Munday, Diane C.', 'Emmott, Edward', 'Surtees, Rebecca', 'Lardeau, Charles-Hugues', 'Wu, Weining', 'Duprex, W. Paul', 'Dove, Brian K.', 'Barr, John N.', 'Hiscox, Julian A.']",Mol Cell Proteomics,,,True
2aa0a28e4246f367ffe104837e755b28d2021f45,PMC,Severe novel influenza A (H1N1) infection in cancer patients,http://dx.doi.org/10.1093/annonc/mdq254,PMC2990816,20511340,CC BY-NC,"Background: The natural history and consequences of severe H1N1 influenza infection among cancer patients are not yet fully characterized. We describe eight cases of H1N1 infection in cancer patients admitted to the intensive care unit of a referral cancer center. Patients and methods: Clinical data from all patients admitted with acute respiratory failure due to novel viral H1N1 infection were reviewed. Lung tissue was submitted for viral and bacteriological analyses by real-time RT-PCR, and autopsy was conducted on all patients who died. Results: Eight patients were admitted, with ages ranging from 55 to 65 years old. There were five patients with solid organ tumors (62.5%) and three with hematological malignancies (37.5%). Five patients required mechanical ventilation and all died. Four patients had bacterial bronchopneumonia. All deaths occurred due to multiple organ failure. A milder form of lung disease was present in the three cases who survived. Lung tissue analysis was performed in all patients and showed diffuse alveolar damage in most patients. Other lung findings were necrotizing bronchiolitis or extensive hemorrhage. Conclusions: H1N1 viral infection in patients with cancer can cause severe illness, resulting in acute respiratory distress syndrome and death. More data are needed to identify predictors of unfavorable evolution in these patients.",2010 Dec 28,"['Hajjar, L. A.', 'Mauad, T.', 'Galas, F. R. B. G.', 'Kumar, A.', 'da Silva, L. F. F.', 'Dolhnikoff, M.', 'Trielli, T.', 'Almeida, J. P.', 'Borsato, M. R. L.', 'Abdalla, E.', 'Pierrot, L.', 'Kalil Filho, R.', 'Auler, J. O. C.', 'Saldiva, P. H. N.', 'Hoff, P. M.']",Ann Oncol,,,True
14c6f99cf0ec54c78447ad5a8403e3ee2708176f,PMC,Contributions of international cooperation projects to the HIV/AIDS response in China,http://dx.doi.org/10.1093/ije/dyq208,PMC2992613,21113032,CC BY-NC,"Background For 20 years, China has participated in 267 international cooperation projects against the HIV/AIDS epidemic and received ∼526 million USD from over 40 international organizations. These projects have played an important role by complementing national efforts in the fight against HIV/AIDS in China. Methods The diverse characteristics of these projects followed three phases over 20 years. Initially, stand-alone projects provided technical support in surveillance, training or advocacy for public awareness. As the epidemic spread across China, projects became a part of the comprehensive and integrated national response. Currently, international best practices encourage the inclusion of civil society and non-governmental organizations in an expanded response to the epidemic. Results Funding from international projects has accounted for one-third of the resources provided for the HIV/AIDS response in China. Beyond this strong financial support, these programmes have introduced best practices, accelerated the introduction of AIDS policies, strengthened capacity, improved the development of grassroots social organizations and established a platform for communication and experience sharing with the international community. However, there are still challenges ahead, including integrating existing resources and exploring new programme models. The National Centre for AIDS/STD Control and Prevention (NCAIDS) in China is consolidating all international projects into national HIV prevention, treatment and care activities. Conclusion International cooperation projects have been an invaluable component of China’s response to HIV/AIDS, and China has now been able to take this information and share its experiences with other countries with the help of these same international programmes.",2010 Dec 24,"['Sun, Jiangping', 'Liu, Hui', 'Li, Hui', 'Wang, Liqiu', 'Guo, Haoyan', 'Shan, Duo', 'Bulterys, Marc', 'Korhonen, Christine', 'Hao, Yang', 'Ren, Minghui']",Int J Epidemiol,,,True
f0599dcb6c670aea2ede76599a9aed614faa92d3,PMC,Evolution of information-driven HIV/AIDS policies in China,http://dx.doi.org/10.1093/ije/dyq217,PMC2992621,21113036,CC BY-NC,"Background As China continues to commit to universal access to HIV/AIDS prevention, treatment and care services, its HIV/AIDS policies have become increasingly information driven. We review China’s key national-level HIV/AIDS policies and discuss policy gaps and challenges ahead. Methods We conducted a desk review of key national-level policies that have had a major impact on China’s HIV/AIDS epidemic, and examined recent epidemiological data relevant to China’s HIV response. Results National-level policies that have had a major impact on China’s HIV/AIDS response include: ‘Four Frees and One Care’; 5-year action plans; and HIV/AIDS regulation. These landmark policies have facilitated massive scaling up of services over the past decade. For example, the number of drug users provided with methadone maintenance treatment significantly increased from 8116 in 2005 to 241 975 in 2009; almost a 30-fold increase. The ‘Four Frees and One Care’ policy has increased the number of people living with AIDS on anti-retroviral treatment from some 100 patients in 2003 to over 80 000 in 2009. However, stigma and discrimination remains major obstacles for people living with HIV/AIDS trying to access services. Conclusions China’s current national policies are increasingly information driven and responsive to changes in the epidemic. However, gaps remain in policy implementation, and new policies are needed to meet emerging challenges.",2010 Dec 24,"['Sun, Xinhua', 'Lu, Fan', 'Wu, Zunyou', 'Poundstone, Katharine', 'Zeng, Gang', 'Xu, Peng', 'Zhang, Dapeng', 'Liu, Kangmai', 'Liau, Adrian']",Int J Epidemiol,,,True
26f94b094ce4d39665edddef1942f04dd041f363,PMC,From spectators to implementers: civil society organizations involved in AIDS programmes in China,http://dx.doi.org/10.1093/ije/dyq223,PMC2992623,21113039,CC BY-NC,"Background Over the past 20 years, civil society organizations (CSOs) in China have significantly increased their involvement in the AIDS response. This article aims to review the extent of civil society participation in China AIDS programmes over the past two decades. Methods A desk review was conducted to collect Chinese government policies, project documents and published articles on civil society participation of HIV/AIDS programmes in China over the past two decades. Assessment focused on five aspects: (i) the political environment; (ii) access to financial resources; (iii) the number of CSOs working on HIV/AIDS; (iv) the scope of work; and (v) the impact of CSO involvement on programmes. Results The number of CSOs specificly working on HIV/AIDS increased from 0 before 1988 to over 400 in 2009. Among a sample of 368 CSOs, 135 (36.7%) were registered. CSOs were primarily supported by international programmes. Government financial support to CSOs has increased from USD248 000 in 2002 to USD1.46 million in 2008. Initially, civil society played a minimal role. It is now widely involved in nearly all aspects of HIV/AIDS-related prevention, treatment and care efforts, and has had a positive impact; for example, increased adherence of anti-retroviral treatment and HIV testing among hard-to-reach groups. The main challenges faced by CSOs include registration, capacity and long-term financial support. Conclusion CSOs have significantly increased their participation and contribution to HIV/AIDS programmes in China. Policies for registration and financial support to CSOs need to be developed to enable them to play an even greater role in AIDS programmes.",2010 Dec 24,"['Li, Hui', 'Kuo, Nana Taona', 'Liu, Hui', 'Korhonen, Christine', 'Pond, Ellenie', 'Guo, Haoyan', 'Smith, Liz', 'Xue, Hui', 'Sun, Jiangping']",Int J Epidemiol,,,True
01b3d789dbd69fff374842fbe2d7f4150fb3d8f5,PMC,Functional analysis of the SRV-1 RNA frameshifting pseudoknot,http://dx.doi.org/10.1093/nar/gkq629,PMC2995055,20639537,CC BY-NC,"Simian retrovirus type-1 uses programmed ribosomal frameshifting to control expression of the Gag-Pol polyprotein from overlapping gag and pol open-reading frames. The frameshifting signal consists of a heptanucleotide slippery sequence and a downstream-located 12-base pair pseudoknot. The solution structure of this pseudoknot, previously solved by NMR [Michiels,P.J., Versleijen,A.A., Verlaan,P.W., Pleij,C.W., Hilbers,C.W. and Heus,H.A. (2001) Solution structure of the pseudoknot of SRV-1 RNA, involved in ribosomal frameshifting. J. Mol. Biol., 310, 1109–1123] has a classical H-type fold and forms an extended triple helix by interactions between loop 2 and the minor groove of stem 1 involving base–base and base–sugar contacts. A mutational analysis was performed to test the functional importance of the triple helix for −1 frameshifting in vitro. Changing bases in L2 or base pairs in S1 involved in a base triple resulted in a 2- to 5-fold decrease in frameshifting efficiency. Alterations in the length of L2 had adverse effects on frameshifting. The in vitro effects were well reproduced in vivo, although the effect of enlarging L2 was more dramatic in vivo. The putative role of refolding kinetics of frameshifter pseudoknots is discussed. Overall, the data emphasize the role of the triple helix in −1 frameshifting.",2010 Nov 17,"['Olsthoorn, René C. L.', 'Reumerman, Richard', 'Hilbers, Cornelis W.', 'Pleij, Cornelis W. A.', 'Heus, Hans A.']",Nucleic Acids Res,,,True
f866dfaccbc646719c85b4103b05ded741a30bee,PMC,Cooperative translocation enhances the unwinding of duplex DNA by SARS coronavirus helicase nsP13,http://dx.doi.org/10.1093/nar/gkq647,PMC2995068,20671029,CC BY-NC,"SARS coronavirus encodes non-structural protein 13 (nsP13), a nucleic acid helicase/NTPase belonging to superfamily 1 helicase, which efficiently unwinds both partial-duplex RNA and DNA. In this study, unwinding of DNA substrates that had different duplex lengths and 5′-overhangs was examined under single-turnover reaction conditions in the presence of excess enzyme. The amount of DNA unwound decreased significantly as the length of the duplex increased, indicating a poor in vitro processivity. However, the quantity of duplex DNA unwound increased as the length of the single-stranded 5′-tail increased for the 50-bp duplex. This enhanced processivity was also observed for duplex DNA that had a longer single-stranded gap in between. These results demonstrate that nsP13 requires the presence of a long 5′-overhang to unwind longer DNA duplexes. In addition, enhanced DNA unwinding was observed for gapped DNA substrates that had a 5′-overhang, indicating that the translocated nsP13 molecules pile up and the preceding helicase facilitate DNA unwinding. Together with the propensity of oligomer formation of nsP13 molecules, we propose that the cooperative translocation by the functionally interacting oligomers of the helicase molecules loaded onto the 5′-overhang account for the observed enhanced processivity of DNA unwinding.",2010 Nov 29,"['Lee, Na-Ra', 'Kwon, Hyun-Mi', 'Park, Kkothanahreum', 'Oh, Sangtaek', 'Jeong, Yong-Joo', 'Kim, Dong-Eun']",Nucleic Acids Res,,,True
02f267368636c422f19d77d3be96de3c0dcbceef,PMC,"Hybridization properties of long nucleic acid probes for detection of variable target sequences, and development of a hybridization prediction algorithm",http://dx.doi.org/10.1093/nar/gkq777,PMC2995084,20864443,CC BY-NC,"One of the main problems in nucleic acid-based techniques for detection of infectious agents, such as influenza viruses, is that of nucleic acid sequence variation. DNA probes, 70-nt long, some including the nucleotide analog deoxyribose-Inosine (dInosine), were analyzed for hybridization tolerance to different amounts and distributions of mismatching bases, e.g. synonymous mutations, in target DNA. Microsphere-linked 70-mer probes were hybridized in 3M TMAC buffer to biotinylated single-stranded (ss) DNA for subsequent analysis in a Luminex® system. When mismatches interrupted contiguous matching stretches of 6 nt or longer, it had a strong impact on hybridization. Contiguous matching stretches are more important than the same number of matching nucleotides separated by mismatches into several regions. dInosine, but not 5-nitroindole, substitutions at mismatching positions stabilized hybridization remarkably well, comparable to N (4-fold) wobbles in the same positions. In contrast to shorter probes, 70-nt probes with judiciously placed dInosine substitutions and/or wobble positions were remarkably mismatch tolerant, with preserved specificity. An algorithm, NucZip, was constructed to model the nucleation and zipping phases of hybridization, integrating both local and distant binding contributions. It predicted hybridization more exactly than previous algorithms, and has the potential to guide the design of variation-tolerant yet specific probes.",2010 Nov 22,"['Öhrmalm, Christina', 'Jobs, Magnus', 'Eriksson, Ronnie', 'Golbob, Sultan', 'Elfaitouri, Amal', 'Benachenhou, Farid', 'Strømme, Maria', 'Blomberg, Jonas']",Nucleic Acids Res,,,True
da4a9038377fc6c4e189376fe271171fc18f8750,PMC,"Hybridization properties of long nucleic acid probes for detection of variable target sequences, and development of a hybridization prediction algorithm",http://dx.doi.org/10.1093/nar/gkq777,PMC2995084,20864443,CC BY-NC,"One of the main problems in nucleic acid-based techniques for detection of infectious agents, such as influenza viruses, is that of nucleic acid sequence variation. DNA probes, 70-nt long, some including the nucleotide analog deoxyribose-Inosine (dInosine), were analyzed for hybridization tolerance to different amounts and distributions of mismatching bases, e.g. synonymous mutations, in target DNA. Microsphere-linked 70-mer probes were hybridized in 3M TMAC buffer to biotinylated single-stranded (ss) DNA for subsequent analysis in a Luminex® system. When mismatches interrupted contiguous matching stretches of 6 nt or longer, it had a strong impact on hybridization. Contiguous matching stretches are more important than the same number of matching nucleotides separated by mismatches into several regions. dInosine, but not 5-nitroindole, substitutions at mismatching positions stabilized hybridization remarkably well, comparable to N (4-fold) wobbles in the same positions. In contrast to shorter probes, 70-nt probes with judiciously placed dInosine substitutions and/or wobble positions were remarkably mismatch tolerant, with preserved specificity. An algorithm, NucZip, was constructed to model the nucleation and zipping phases of hybridization, integrating both local and distant binding contributions. It predicted hybridization more exactly than previous algorithms, and has the potential to guide the design of variation-tolerant yet specific probes.",2010 Nov 22,"['Öhrmalm, Christina', 'Jobs, Magnus', 'Eriksson, Ronnie', 'Golbob, Sultan', 'Elfaitouri, Amal', 'Benachenhou, Farid', 'Strømme, Maria', 'Blomberg, Jonas']",Nucleic Acids Res,,,False
2f202eab94698ac9352253f37500090a865bc3c1,PMC,"Hybridization properties of long nucleic acid probes for detection of variable target sequences, and development of a hybridization prediction algorithm",http://dx.doi.org/10.1093/nar/gkq777,PMC2995084,20864443,CC BY-NC,"One of the main problems in nucleic acid-based techniques for detection of infectious agents, such as influenza viruses, is that of nucleic acid sequence variation. DNA probes, 70-nt long, some including the nucleotide analog deoxyribose-Inosine (dInosine), were analyzed for hybridization tolerance to different amounts and distributions of mismatching bases, e.g. synonymous mutations, in target DNA. Microsphere-linked 70-mer probes were hybridized in 3M TMAC buffer to biotinylated single-stranded (ss) DNA for subsequent analysis in a Luminex® system. When mismatches interrupted contiguous matching stretches of 6 nt or longer, it had a strong impact on hybridization. Contiguous matching stretches are more important than the same number of matching nucleotides separated by mismatches into several regions. dInosine, but not 5-nitroindole, substitutions at mismatching positions stabilized hybridization remarkably well, comparable to N (4-fold) wobbles in the same positions. In contrast to shorter probes, 70-nt probes with judiciously placed dInosine substitutions and/or wobble positions were remarkably mismatch tolerant, with preserved specificity. An algorithm, NucZip, was constructed to model the nucleation and zipping phases of hybridization, integrating both local and distant binding contributions. It predicted hybridization more exactly than previous algorithms, and has the potential to guide the design of variation-tolerant yet specific probes.",2010 Nov 22,"['Öhrmalm, Christina', 'Jobs, Magnus', 'Eriksson, Ronnie', 'Golbob, Sultan', 'Elfaitouri, Amal', 'Benachenhou, Farid', 'Strømme, Maria', 'Blomberg, Jonas']",Nucleic Acids Res,,,False
e0eeb5a73d1f72401b821e2b27bb4b826926bdc8,PMC,"Hybridization properties of long nucleic acid probes for detection of variable target sequences, and development of a hybridization prediction algorithm",http://dx.doi.org/10.1093/nar/gkq777,PMC2995084,20864443,CC BY-NC,"One of the main problems in nucleic acid-based techniques for detection of infectious agents, such as influenza viruses, is that of nucleic acid sequence variation. DNA probes, 70-nt long, some including the nucleotide analog deoxyribose-Inosine (dInosine), were analyzed for hybridization tolerance to different amounts and distributions of mismatching bases, e.g. synonymous mutations, in target DNA. Microsphere-linked 70-mer probes were hybridized in 3M TMAC buffer to biotinylated single-stranded (ss) DNA for subsequent analysis in a Luminex® system. When mismatches interrupted contiguous matching stretches of 6 nt or longer, it had a strong impact on hybridization. Contiguous matching stretches are more important than the same number of matching nucleotides separated by mismatches into several regions. dInosine, but not 5-nitroindole, substitutions at mismatching positions stabilized hybridization remarkably well, comparable to N (4-fold) wobbles in the same positions. In contrast to shorter probes, 70-nt probes with judiciously placed dInosine substitutions and/or wobble positions were remarkably mismatch tolerant, with preserved specificity. An algorithm, NucZip, was constructed to model the nucleation and zipping phases of hybridization, integrating both local and distant binding contributions. It predicted hybridization more exactly than previous algorithms, and has the potential to guide the design of variation-tolerant yet specific probes.",2010 Nov 22,"['Öhrmalm, Christina', 'Jobs, Magnus', 'Eriksson, Ronnie', 'Golbob, Sultan', 'Elfaitouri, Amal', 'Benachenhou, Farid', 'Strømme, Maria', 'Blomberg, Jonas']",Nucleic Acids Res,,,False
c95254fd470f76348e4b2c7c13ff76bba8b1ecac,PMC,"Hybridization properties of long nucleic acid probes for detection of variable target sequences, and development of a hybridization prediction algorithm",http://dx.doi.org/10.1093/nar/gkq777,PMC2995084,20864443,CC BY-NC,"One of the main problems in nucleic acid-based techniques for detection of infectious agents, such as influenza viruses, is that of nucleic acid sequence variation. DNA probes, 70-nt long, some including the nucleotide analog deoxyribose-Inosine (dInosine), were analyzed for hybridization tolerance to different amounts and distributions of mismatching bases, e.g. synonymous mutations, in target DNA. Microsphere-linked 70-mer probes were hybridized in 3M TMAC buffer to biotinylated single-stranded (ss) DNA for subsequent analysis in a Luminex® system. When mismatches interrupted contiguous matching stretches of 6 nt or longer, it had a strong impact on hybridization. Contiguous matching stretches are more important than the same number of matching nucleotides separated by mismatches into several regions. dInosine, but not 5-nitroindole, substitutions at mismatching positions stabilized hybridization remarkably well, comparable to N (4-fold) wobbles in the same positions. In contrast to shorter probes, 70-nt probes with judiciously placed dInosine substitutions and/or wobble positions were remarkably mismatch tolerant, with preserved specificity. An algorithm, NucZip, was constructed to model the nucleation and zipping phases of hybridization, integrating both local and distant binding contributions. It predicted hybridization more exactly than previous algorithms, and has the potential to guide the design of variation-tolerant yet specific probes.",2010 Nov 22,"['Öhrmalm, Christina', 'Jobs, Magnus', 'Eriksson, Ronnie', 'Golbob, Sultan', 'Elfaitouri, Amal', 'Benachenhou, Farid', 'Strømme, Maria', 'Blomberg, Jonas']",Nucleic Acids Res,,,False
3847e4c86669d7fb99aaf66b28146959a24af61b,PMC,"Hybridization properties of long nucleic acid probes for detection of variable target sequences, and development of a hybridization prediction algorithm",http://dx.doi.org/10.1093/nar/gkq777,PMC2995084,20864443,CC BY-NC,"One of the main problems in nucleic acid-based techniques for detection of infectious agents, such as influenza viruses, is that of nucleic acid sequence variation. DNA probes, 70-nt long, some including the nucleotide analog deoxyribose-Inosine (dInosine), were analyzed for hybridization tolerance to different amounts and distributions of mismatching bases, e.g. synonymous mutations, in target DNA. Microsphere-linked 70-mer probes were hybridized in 3M TMAC buffer to biotinylated single-stranded (ss) DNA for subsequent analysis in a Luminex® system. When mismatches interrupted contiguous matching stretches of 6 nt or longer, it had a strong impact on hybridization. Contiguous matching stretches are more important than the same number of matching nucleotides separated by mismatches into several regions. dInosine, but not 5-nitroindole, substitutions at mismatching positions stabilized hybridization remarkably well, comparable to N (4-fold) wobbles in the same positions. In contrast to shorter probes, 70-nt probes with judiciously placed dInosine substitutions and/or wobble positions were remarkably mismatch tolerant, with preserved specificity. An algorithm, NucZip, was constructed to model the nucleation and zipping phases of hybridization, integrating both local and distant binding contributions. It predicted hybridization more exactly than previous algorithms, and has the potential to guide the design of variation-tolerant yet specific probes.",2010 Nov 22,"['Öhrmalm, Christina', 'Jobs, Magnus', 'Eriksson, Ronnie', 'Golbob, Sultan', 'Elfaitouri, Amal', 'Benachenhou, Farid', 'Strømme, Maria', 'Blomberg, Jonas']",Nucleic Acids Res,,,False
d892d02ec48235a6a09521f84a05ffe5e1a89aaa,PMC,"Hybridization properties of long nucleic acid probes for detection of variable target sequences, and development of a hybridization prediction algorithm",http://dx.doi.org/10.1093/nar/gkq777,PMC2995084,20864443,CC BY-NC,"One of the main problems in nucleic acid-based techniques for detection of infectious agents, such as influenza viruses, is that of nucleic acid sequence variation. DNA probes, 70-nt long, some including the nucleotide analog deoxyribose-Inosine (dInosine), were analyzed for hybridization tolerance to different amounts and distributions of mismatching bases, e.g. synonymous mutations, in target DNA. Microsphere-linked 70-mer probes were hybridized in 3M TMAC buffer to biotinylated single-stranded (ss) DNA for subsequent analysis in a Luminex® system. When mismatches interrupted contiguous matching stretches of 6 nt or longer, it had a strong impact on hybridization. Contiguous matching stretches are more important than the same number of matching nucleotides separated by mismatches into several regions. dInosine, but not 5-nitroindole, substitutions at mismatching positions stabilized hybridization remarkably well, comparable to N (4-fold) wobbles in the same positions. In contrast to shorter probes, 70-nt probes with judiciously placed dInosine substitutions and/or wobble positions were remarkably mismatch tolerant, with preserved specificity. An algorithm, NucZip, was constructed to model the nucleation and zipping phases of hybridization, integrating both local and distant binding contributions. It predicted hybridization more exactly than previous algorithms, and has the potential to guide the design of variation-tolerant yet specific probes.",2010 Nov 22,"['Öhrmalm, Christina', 'Jobs, Magnus', 'Eriksson, Ronnie', 'Golbob, Sultan', 'Elfaitouri, Amal', 'Benachenhou, Farid', 'Strømme, Maria', 'Blomberg, Jonas']",Nucleic Acids Res,,,False
924dc69ab73fbedf0c55ba2f7cd22e76710512ea,PMC,High Rate of Viral Identification and Coinfections in Infants with Acute Bronchiolitis,http://dx.doi.org/10.1590/S1807-59322010001100014,PMC2999709,21243286,CC BY-NC,"OBJECTIVES: To determine the viruses and risk factors associated with hospital and intensive care unit (ICU) admissions in infants with acute bronchiolitis. INTRODUCTION: Bronchiolitis is a major cause of morbidity in infants. Widespread use of molecular-based methods has yielded new insights about its etiology, but the impact of viral etiologies on early outcomes is still unclear. METHODS: Seventy-seven infants with bronchiolitis who were under two years of age and visited an emergency unit were included. Using molecular-based methods, samples were tested for 12 different respiratory viruses. Logistic regression models were used to identify clinical and virological variables associated with the main endpoints: hospital admission and ICU admission. RESULTS: We identified at least one virus in 93.5% of patients, and coinfections were found in nearly 40% of patients. RSV was the most common pathogen (63.6%), followed by rhinovirus (39%). Identification of RSV was only associated with an increased risk of hospital admission in the univariate model. Younger age and enterovirus infection were associated with an increased risk of hospital admission, while atopy of a first-degree relative showed a protective effect. Prematurity was associated with an increased risk of admission to the ICU. Coinfections were not associated with worse outcomes. CONCLUSIONS: Molecular-based methods resulted in high rates of viral identification but did not change the significant role of RSV in acute bronchiolitis. Younger age and enterovirus infection were risk factors for hospital admission, while prematurity appeared to be a significant risk factor for admission to the ICU in acute viral bronchiolitis.",2010 Nov,"['Nascimento, Milena Siciliano', 'de Souza, Andréa Vieira', 'de Souza Ferreira, Adriana Vada', 'Rodrigues, Joaquim Carlos', 'Abramovici, Sulim', 'da Silva Filho, Luiz Vicente Ferreira']",Clinics (Sao Paulo),,,True
8fefbc58375c244a64a82e3f88c4084076838b88,PMC,Rotavirus Disrupts Calcium Homeostasis by NSP4 Viroporin Activity,http://dx.doi.org/10.1128/mBio.00265-10,PMC2999940,21151776,CC BY-NC-SA,"Many viruses alter intracellular calcium homeostasis. The rotavirus nonstructural protein 4 (NSP4), an endoplasmic reticulum (ER) transmembrane glycoprotein, increases intracellular levels of cytoplasmic Ca(2+) ([Ca(2+)]cyto) through a phospholipase C-independent pathway, which is required for virus replication and morphogenesis. However, the NSP4 domain and mechanism that increases [Ca(2+)]cyto are unknown. We identified an NSP4 domain (amino acids [aa] 47 to 90) that inserts into membranes and has structural characteristics of viroporins, a class of small hydrophobic viral proteins that disrupt membrane integrity and ion homeostasis to facilitate virus entry, assembly, or release. Mutational analysis showed that NSP4 viroporin activity was mediated by an amphipathic α-helical domain downstream of a conserved lysine cluster. The lysine cluster directed integral membrane insertion of the viroporin domain and was critical for viroporin activity. In epithelial cells, expression of wild-type NSP4 increased the levels of free cytoplasmic Ca(2+) by 3.7-fold, but NSP4 viroporin mutants maintained low levels of [Ca(2+)]cyto, were retained in the ER, and failed to form cytoplasmic vesicular structures, called puncta, which surround viral replication and assembly sites in rotavirus-infected cells. When [Ca(2+)]cyto was increased pharmacologically with thapsigargin, viroporin mutants formed puncta, showing that elevation of calcium levels and puncta formation are distinct functions of NSP4 and indicating that NSP4 directly or indirectly responds to elevated cytoplasmic calcium levels. NSP4 viroporin activity establishes the mechanism for NSP4-mediated elevation of [Ca(2+)]cyto, a critical event that regulates rotavirus replication and virion assembly.",2010 Nov 30,"['Hyser, Joseph M.', 'Collinson-Pautz, Matthew R.', 'Utama, Budi', 'Estes, Mary K.']",mBio,,,True
f619b2eb37e9970f65936ac361feb22743395e65,PMC,Rotavirus Disrupts Calcium Homeostasis by NSP4 Viroporin Activity,http://dx.doi.org/10.1128/mBio.00265-10,PMC2999940,21151776,CC BY-NC-SA,"Many viruses alter intracellular calcium homeostasis. The rotavirus nonstructural protein 4 (NSP4), an endoplasmic reticulum (ER) transmembrane glycoprotein, increases intracellular levels of cytoplasmic Ca(2+) ([Ca(2+)]cyto) through a phospholipase C-independent pathway, which is required for virus replication and morphogenesis. However, the NSP4 domain and mechanism that increases [Ca(2+)]cyto are unknown. We identified an NSP4 domain (amino acids [aa] 47 to 90) that inserts into membranes and has structural characteristics of viroporins, a class of small hydrophobic viral proteins that disrupt membrane integrity and ion homeostasis to facilitate virus entry, assembly, or release. Mutational analysis showed that NSP4 viroporin activity was mediated by an amphipathic α-helical domain downstream of a conserved lysine cluster. The lysine cluster directed integral membrane insertion of the viroporin domain and was critical for viroporin activity. In epithelial cells, expression of wild-type NSP4 increased the levels of free cytoplasmic Ca(2+) by 3.7-fold, but NSP4 viroporin mutants maintained low levels of [Ca(2+)]cyto, were retained in the ER, and failed to form cytoplasmic vesicular structures, called puncta, which surround viral replication and assembly sites in rotavirus-infected cells. When [Ca(2+)]cyto was increased pharmacologically with thapsigargin, viroporin mutants formed puncta, showing that elevation of calcium levels and puncta formation are distinct functions of NSP4 and indicating that NSP4 directly or indirectly responds to elevated cytoplasmic calcium levels. NSP4 viroporin activity establishes the mechanism for NSP4-mediated elevation of [Ca(2+)]cyto, a critical event that regulates rotavirus replication and virion assembly.",2010 Nov 30,"['Hyser, Joseph M.', 'Collinson-Pautz, Matthew R.', 'Utama, Budi', 'Estes, Mary K.']",mBio,,,False
8d21989761b3a358d565559bade36a9b8654dd78,PMC,Stimulation of ribosomal frameshifting by antisense LNA,http://dx.doi.org/10.1093/nar/gkq650,PMC3001050,20693527,CC BY-NC,"Programmed ribosomal frameshifting is a translational recoding mechanism commonly used by RNA viruses to express two or more proteins from a single mRNA at a fixed ratio. An essential element in this process is the presence of an RNA secondary structure, such as a pseudoknot or a hairpin, located downstream of the slippery sequence. Here, we have tested the efficiency of RNA oligonucleotides annealing downstream of the slippery sequence to induce frameshifting in vitro. Maximal frameshifting was observed with oligonucleotides of 12–18 nt. Antisense oligonucleotides bearing locked nucleid acid (LNA) modifications also proved to be efficient frameshift-stimulators in contrast to DNA oligonucleotides. The number, sequence and location of LNA bases in an otherwise DNA oligonucleotide have to be carefully manipulated to obtain optimal levels of frameshifting. Our data favor a model in which RNA stability at the entrance of the ribosomal tunnel is the major determinant of stimulating slippage rather than a specific three-dimensional structure of the stimulating RNA element.",2010 Dec 6,"['Yu, Chien-Hung', 'Noteborn, Mathieu H. M.', 'Olsthoorn, René C. L.']",Nucleic Acids Res,,,True
808ed8eb35c9674d24e464888c76c898ea979691,PMC,The intracellular dynamic of protein palmitoylation,http://dx.doi.org/10.1083/jcb.201008160,PMC3010063,21187327,CC BY-NC-SA,"S-palmitoylation describes the reversible attachment of fatty acids (predominantly palmitate) onto cysteine residues via a labile thioester bond. This posttranslational modification impacts protein functionality by regulating membrane interactions, intracellular sorting, stability, and membrane micropatterning. Several recent findings have provided a tantalizing insight into the regulation and spatiotemporal dynamics of protein palmitoylation. In mammalian cells, the Golgi has emerged as a possible super-reaction center for the palmitoylation of peripheral membrane proteins, whereas palmitoylation reactions on post-Golgi compartments contribute to the regulation of specific substrates. In addition to palmitoylating and depalmitoylating enzymes, intracellular palmitoylation dynamics may also be controlled through interplay with distinct posttranslational modifications, such as phosphorylation and nitrosylation.",2010 Dec 27,"['Salaun, Christine', 'Greaves, Jennifer', 'Chamberlain, Luke H.']",J Cell Biol,,,True
f7c0f747be302193f876a3d3ddf1e14098090e75,PMC,PhEVER: a database for the global exploration of virus–host evolutionary relationships,http://dx.doi.org/10.1093/nar/gkq1013,PMC3013642,21081560,CC BY-NC,"Fast viral adaptation and the implication of this rapid evolution in the emergence of several new infectious diseases have turned this issue into a major challenge for various research domains. Indeed, viruses are involved in the development of a wide range of pathologies and understanding how viruses and host cells interact in the context of adaptation remains an open question. In order to provide insights into the complex interactions between viruses and their host organisms and namely in the acquisition of novel functions through exchanges of genetic material, we developed the PhEVER database. This database aims at providing accurate evolutionary and phylogenetic information to analyse the nature of virus–virus and virus–host lateral gene transfers. PhEVER (http://pbil.univ-lyon1.fr/databases/phever) is a unique database of homologous families both (i) between sequences from different viruses and (ii) between viral sequences and sequences from cellular organisms. PhEVER integrates extensive data from up-to-date completely sequenced genomes (2426 non-redundant viral genomes, 1007 non-redundant prokaryotic genomes, 43 eukaryotic genomes ranging from plants to vertebrates) and offers a clustering of proteins into homologous families containing at least one viral sequences, as well as alignments and phylogenies for each of these families. Public access to PhEVER is available through its webpage and through all dedicated ACNUC retrieval systems.",2011 Jan 16,"['Palmeira, Leonor', 'Penel, Simon', 'Lotteau, Vincent', 'Rabourdin-Combe, Chantal', 'Gautier, Christian']",Nucleic Acids Res,,,True
418d9334932cd1b03e23fd6e03c01e660fff4bd4,PMC,The many paths to frameshifting: kinetic modelling and analysis of the effects of different elongation steps on programmed –1 ribosomal frameshifting,http://dx.doi.org/10.1093/nar/gkq761,PMC3017607,20823091,CC BY-NC,"Several important viruses including the human immunodeficiency virus type 1 (HIV-1) and the SARS-associated Coronavirus (SARS-CoV) employ programmed −1 ribosomal frameshifting (PRF) for their protein expression. Here, a kinetic framework is developed to describe −1 PRF. The model reveals three kinetic pathways to −1 PRF that yield two possible frameshift products: those incorporating zero frame encoded A-site tRNAs in the recoding site, and products incorporating −1 frame encoded A-site tRNAs. Using known kinetic rate constants, the individual contributions of different steps of the translation elongation cycle to −1 PRF and the ratio between two types of frameshift products were evaluated. A dual fluorescence reporter was employed in Escherichia coli to empirically test the model. Additionally, the study applied a novel mass spectrometry approach to quantify the ratios of the two frameshift products. A more detailed understanding of the mechanisms underlying −1 PRF may provide insight into developing antiviral therapeutics.",2011 Jan 7,"['Liao, Pei-Yu', 'Choi, Yong Seok', 'Dinman, Jonathan D.', 'Lee, Kelvin H.']",Nucleic Acids Res,,,True
84da44d2366d3f082d0ec30cbaff70807ca732c7,PMC,Perception and Performance of Preventive Behaviors for the Pandemic Influenza in Hospital Employees and Outpatients,http://dx.doi.org/10.3349/ymj.2011.52.1.181,PMC3017695,21155052,CC BY-NC,"PURPOSE: A new strain of the H1N1 subtype of influenza A virus resulted in a pandemic outbreak. In South Korea, cases of pandemic influenza have increased. Therefore, we explored perception or preventive behaviors for this virus in hospital employees and outpatients. MATERIALS AND METHODS: Data was collected from hospital employees and outpatients at three university hospitals located in Daegu, Gyeongju in South Korea between the 21st and 30th of September, 2009 using a self-administrated questionnaire. We estimated perception by components of The Health Belief Model (HBM), preventive behaviors consisted of avoidance behaviors, and the recommended behaviors by the Korea Center of Disease Control and Prevention (KCDC). Desire for vaccination was identified. RESULTS: The 1,837 participants comprised hospital employees (n = 880, 47.9%) and outpatients (n = 957, 52.1%). Of all hospital employees, 491 (55.8%) and 708 (80.5%) perceived susceptibility of the pandemic influenza and benefits of the preventive behaviors, respectively. Among all outpatients, 490 (51.2%) and 651 (68.0%) perceived susceptibility of the pandemic influenza and benefits of the preventive behaviors, respectively. Recommended preventative behaviors were adopted by 674 (76.6%) of hospital employees and 631 (65.9%) of outpatients. Vaccination was desired by 479 (54.4%) of hospital employees and 484 (50.6%) of outpatients. Factors influencing preventative behaviors included gender, economic status (for hospital employees) and educational level (for outpatients). All HBM components except perception of barriers were associated with the preventive behaviors in both groups. CONCLUSION: The majority of the surveyed hospital employees and outpatients perceived the benefits of preventive behaviors for pandemic influenza and performed them.",2011 Jan 1,"['Jeong, Hwee Soo', 'Lee, Dong Wook', 'Youn, Chang Ho', 'Lee, Mi Kyung', 'Lee, Seung Jun', 'Suh, Young Sung', 'Kim, Dae Hyun']",Yonsei Med J,,,True
f12dac6dd672f51fbf89bec56df7f7a8af5331df,PMC,Pathological and ultrastructural analysis of surgical lung biopsies in patients with swine‐origin influenza type A/H1N1 and acute respiratory failure,http://dx.doi.org/10.1590/S1807-59322010001200003,PMC3020331,21340209,CC BY-NC,"BACKGROUND: Cases of H1N1 and other pulmonary infections evolve to acute respiratory failure and death when co‐infections or lung injury predominate over the immune response, thus requiring early diagnosis to improve treatment. OBJECTIVE: To perform a detailed histopathological analysis of the open lung biopsy specimens from five patients with ARDS with confirmed H1N1. METHODS: Lung specimens underwent microbiologic analysis, and examination by optical and electron microscopy. Immunophenotyping was used to characterize macrophages, natural killer, T and B cells, and expression of cytokines and iNOS. RESULTS: The pathological features observed were necrotizing bronchiolitis, diffuse alveolar damage, alveolar hemorrhage and abnormal immune response. Ultrastructural analysis showed viral‐like particles in all cases. CONCLUSIONS: Viral‐like particles can be successfully demonstrated in lung tissue by ultrastructural examination, without confirmation of the virus by RT‐PCR on nasopharyngeal aspirates. Bronchioles and epithelium, rather than endothelium, are probably the primary target of infection, and diffuse alveolar damage the consequence of the effect of airways obliteration and dysfunction on innate immunity, suggesting that treatment should be focused on epithelial repair.",2010 Dec,"['Capelozzi, Vera Luiza', 'Parra, Edwin Roger', 'Ximenes, Manoel', 'Bammann, Ricardo Helbert', 'Barbas, Carmen Silvia Valente', 'Duarte, Marid Irmd Seixas']",Clinics (Sao Paulo),,,True
3cf33ae7aecff3052d051eefe7f4d26287c0217d,PMC,SHIP deficiency causes Crohn's disease-like ileitis,http://dx.doi.org/10.1136/gut.2009.202283,PMC3022365,20940287,CC BY-NC,"BACKGROUND: Inflammatory bowel disease (IBD) can arise from genetic mutations that compromise intestinal epithelial cell integrity or immune regulation. SHIP has previously been shown to play a pivotal role in limiting the number of immunoregulatory cells and their function. AIM: To determine whether SHIP plays a pivotal role in control of immune tolerance in the gut mucosa. METHODS: Gastrointestinal pathology was assessed in three separate strains of SHIP-deficient mice and their respective wild-type (WT) littermates. Gastrointestinal pathology was analysed in SHIP-deficient hosts reconstituted with WT haematopoietic cell grafts, and WT hosts reconstituted with SHIP-deficient haematopoietic cell grafts including whole splenocytes, purified T cells or natural killer (NK) cells. Major immune cell populations were also analysed in the small intestine of SHIP-deficient mice and WT controls. RESULTS: SHIP-deficient mice developed segmental, transmural pyo-granulomatous ilietis that recapitulated classical features of Crohn's disease enteric pathology. Analysis of haematopoietic chimeras showed that WT bone marrow reconstitution of SHIP(−/−) hosts corrects ileitis. Reconstitution with SHIP(−/−) splenocytes transferred ileitis to WT hosts. Adoptive transfer of purified SHIP(−/−) T cells or NK cells to WT hosts did not transfer ileitis. There was a paucity of both CD4 and CD8 T cells in the small intestines of SHIP-deficient mice; however, neutrophil numbers were significantly increased. CONCLUSIONS: SHIP plays a pivotal role in immune function in the intestine; further scrutiny of this pathway in IBD patients is warranted. It is proposed that SHIP-deficient ileitis results from a local deficit in mucosal T cell immunity that promotes a damaging granulocyte–monocyte inflammation of the distal ileum.",2011 Feb 12,"['Kerr, William G', 'Park, Mi-Young', 'Maubert, Monique', 'Engelman, Robert W']",Gut,,,True
9e7e20f7b3fcd74b3f899215f18e096c30fec048,PMC,Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection,http://dx.doi.org/10.1084/jem.20101352,PMC3023136,21220454,CC BY-NC-SA,"The 2009 pandemic H1N1 influenza pandemic demonstrated the global health threat of reassortant influenza strains. Herein, we report a detailed analysis of plasmablast and monoclonal antibody responses induced by pandemic H1N1 infection in humans. Unlike antibodies elicited by annual influenza vaccinations, most neutralizing antibodies induced by pandemic H1N1 infection were broadly cross-reactive against epitopes in the hemagglutinin (HA) stalk and head domain of multiple influenza strains. The antibodies were from cells that had undergone extensive affinity maturation. Based on these observations, we postulate that the plasmablasts producing these broadly neutralizing antibodies were predominantly derived from activated memory B cells specific for epitopes conserved in several influenza strains. Consequently, most neutralizing antibodies were broadly reactive against divergent H1N1 and H5N1 influenza strains. This suggests that a pan-influenza vaccine may be possible, given the right immunogen. Antibodies generated potently protected and rescued mice from lethal challenge with pandemic H1N1 or antigenically distinct influenza strains, making them excellent therapeutic candidates.",2011 Jan 17,"['Wrammert, Jens', 'Koutsonanos, Dimitrios', 'Li, Gui-Mei', 'Edupuganti, Srilatha', 'Sui, Jianhua', 'Morrissey, Michael', 'McCausland, Megan', 'Skountzou, Ioanna', 'Hornig, Mady', 'Lipkin, W. Ian', 'Mehta, Aneesh', 'Razavi, Behzad', 'Del Rio, Carlos', 'Zheng, Nai-Ying', 'Lee, Jane-Hwei', 'Huang, Min', 'Ali, Zahida', 'Kaur, Kaval', 'Andrews, Sarah', 'Amara, Rama Rao', 'Wang, Youliang', 'Das, Suman Ranjan', ""O'Donnell, Christopher David"", 'Yewdell, Jon W.', 'Subbarao, Kanta', 'Marasco, Wayne A.', 'Mulligan, Mark J.', 'Compans, Richard', 'Ahmed, Rafi', 'Wilson, Patrick C.']",J Exp Med,,,True
ccb533d872f914aee01fd533f330c6d768da14c5,PMC,Animal Models of Cardiac Disease and Stem Cell Therapy,http://dx.doi.org/10.2174/1874192401004010231,PMC3024564,21258568,CC BY-NC,"Animal models that mimic cardiovascular diseases are indispensable tools for understanding the mechanisms underlying the diseases at the cellular and molecular level. This review focuses on various methods in preclinical research to create small animal models of cardiac diseases, such as myocardial infarction, dilated cardiomyopathy, heart failure, myocarditis and cardiac hypertrophy, and the related stem cell treatment for these diseases.",2010 Nov 26,"['Ou, Lailiang', 'Li, Wenzhong', 'Liu, Yi', 'Zhang, Yue', 'Jie, Shen', 'Kong, Deling', 'Steinhoff, Gustav', 'Ma, Nan']",Open Cardiovasc Med J,,,True
ac29d39e0b59cf2d1469af974756f5efbf3c26dd,PMC,PCAF interacts with XBP-1S and mediates XBP-1S-dependent transcription,http://dx.doi.org/10.1093/nar/gkq785,PMC3025546,20817929,CC BY-NC,"X-box binding protein 1 (XBP-1) is a key regulator required for cellular unfolded protein response (UPR) and plasma cell differentiation. In addition, involvement of XBP-1 in host cell–virus interaction and transcriptional regulation of viruses, such as human T-lymphotropic virus type 1 (HTLV-1), has been revealed recently. Two XBP-1 isoforms, XBP-1U and XBP-1S, which share an identical N-terminal domain, are present in cells. XBP-1S is a transcription activator while XBP-1U is the inactive isoform. Although the transactivation domain of XBP-1S has been identified within the XBP-1S-specific C-terminus, molecular mechanism of the transcriptional activation by XBP-1S still remains unknown. Here we report the interaction between p300/CBP-associated factor (PCAF) and XBP-1S through the C-terminal domain of XBP-1S. No binding between XBP-1U and PCAF is detected. In a cell-based reporter assay, overexpression of PCAF further stimulates the XBP-1S-mediated cellular and HTLV-1 transcription while knockdown of PCAF exhibits the opposite effect. Expression of endogenous XBP-1S cellular target genes, such as BiP and CHOP, is significantly inhibited when PCAF is knocked down. Furthermore, PCAF is recruited to the promoters of XBP-1S target genes in vivo, in a XBP-1S-dependent manner. Collectively, our results demonstrate that PCAF mediates the XBP-1S-dependent transcription through the interaction with XBP-1S.",2011 Jan 4,"['Lew, Qiao Jing', 'Chu, Kai Ling', 'Lee, Jialing', 'Koh, Poh Ling', 'Rajasegaran, Vikneswari', 'Teo, Jin Yuan', 'Chao, Sheng-Hao']",Nucleic Acids Res,,,True
1f71a8f9029056b6e7656ebd885ccce476e2f623,PMC,A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm,http://dx.doi.org/10.1128/mBio.00325-10,PMC3034460,21285433,CC BY-NC-SA,"The twentieth century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and waterborne illnesses are frequent, multidrug-resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the past—including the intense focus on individual genes and proteins typical of molecular biology—have not been sufficient to address these challenges. The first decade of the twenty-first century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondingly deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program, we think that the time is at hand to redefine the pathogen-host research paradigm.",2011 Feb 1,"['Aderem, Alan', 'Adkins, Joshua N.', 'Ansong, Charles', 'Galagan, James', 'Kaiser, Shari', 'Korth, Marcus J.', 'Law, G. Lynn', 'McDermott, Jason G.', 'Proll, Sean C.', 'Rosenberger, Carrie', 'Schoolnik, Gary', 'Katze, Michael G.']",mBio,,,True
21337e54a7d02b12aea5f5835648d69aef32701e,PMC,The activity of the HIV-1 IRES is stimulated by oxidative stress and controlled by a negative regulatory element,http://dx.doi.org/10.1093/nar/gkq885,PMC3035469,20935056,CC BY-NC,"Initiation of translation of the full-length messenger RNA of HIV-1, which generates the viral structural proteins and enzymes, is cap-dependent but can also use an internal ribosome entry site (IRES) located in the 5′ untranslated region. Our aim was to define, through a mutational analysis, regions of HIV-1 IRES that are important for its activity. A dual-luciferase reporter construct where the Renilla luciferase (Rluc) translation is cap-dependent while the firefly luciferase (Fluc) translation depends on HIV-1 IRES was used. The Fluc/Rluc ratio was measured in lysates of Jurkat T cells transfected with the dual-luciferase plasmid bearing either the wild-type or a mutated IRES. Deletions or mutations in three regions decreased the IRES activity but deletion or mutations of a stem-loop preceding the primer binding site increased the IRES activity. The wild-type IRES activity, but not that of an IRES with a mutated stem-loop, was increased when cells were treated with agents that induce oxidative stress. Such stress is known to be caused by HIV-1 infection and we propose that this stem-loop is involved in a switch that stimulates the IRES activity in cells infected with HIV-1, supporting the suggestion that the IRES activity is up-regulated in the course of HIV-1 replication cycle.",2011 Feb 8,"['Gendron, Karine', 'Ferbeyre, Gerardo', 'Heveker, Nikolaus', 'Brakier-Gingras, Léa']",Nucleic Acids Res,,,True
54e77bff1912076bccf12a6b099e48a59f634d5f,PMC,The activity of the HIV-1 IRES is stimulated by oxidative stress and controlled by a negative regulatory element,http://dx.doi.org/10.1093/nar/gkq885,PMC3035469,20935056,CC BY-NC,"Initiation of translation of the full-length messenger RNA of HIV-1, which generates the viral structural proteins and enzymes, is cap-dependent but can also use an internal ribosome entry site (IRES) located in the 5′ untranslated region. Our aim was to define, through a mutational analysis, regions of HIV-1 IRES that are important for its activity. A dual-luciferase reporter construct where the Renilla luciferase (Rluc) translation is cap-dependent while the firefly luciferase (Fluc) translation depends on HIV-1 IRES was used. The Fluc/Rluc ratio was measured in lysates of Jurkat T cells transfected with the dual-luciferase plasmid bearing either the wild-type or a mutated IRES. Deletions or mutations in three regions decreased the IRES activity but deletion or mutations of a stem-loop preceding the primer binding site increased the IRES activity. The wild-type IRES activity, but not that of an IRES with a mutated stem-loop, was increased when cells were treated with agents that induce oxidative stress. Such stress is known to be caused by HIV-1 infection and we propose that this stem-loop is involved in a switch that stimulates the IRES activity in cells infected with HIV-1, supporting the suggestion that the IRES activity is up-regulated in the course of HIV-1 replication cycle.",2011 Feb 8,"['Gendron, Karine', 'Ferbeyre, Gerardo', 'Heveker, Nikolaus', 'Brakier-Gingras, Léa']",Nucleic Acids Res,,,True
a654354060fcce82810e2c8842195d7e16995d11,PMC,High-Dose Mannose-Binding Lectin Therapy for Ebola Virus Infection,http://dx.doi.org/10.1093/infdis/jiq025,PMC3071052,21288816,CC BY-NC,"Mannose-binding lectin (MBL) targets diverse microorganisms for phagocytosis and complement-mediated lysis by binding specific surface glycans. Although recombinant human MBL (rhMBL) trials have focused on reconstitution therapy, safety studies have identified no barriers to its use at higher levels. Ebola viruses cause fatal hemorrhagic fevers for which no treatment exists and that are feared as potential biothreat agents. We found that mice whose rhMBL serum concentrations were increased ≥7-fold above average human levels survived otherwise fatal Ebola virus infections and became immune to virus rechallenge. Because Ebola glycoproteins potentially model other glycosylated viruses, rhMBL may offer a novel broad-spectrum antiviral approach.",2011 Jan 15,"['Michelow, Ian C.', 'Lear, Calli', 'Scully, Corinne', 'Prugar, Laura I.', 'Longley, Clifford B.', 'Yantosca, L. Michael', 'Ji, Xin', 'Karpel, Marshall', 'Brudner, Matthew', 'Takahashi, Kazue', 'Spear, Gregory T.', 'Ezekowitz, R. Alan B.', 'Schmidt, Emmett V.', 'Olinger, Gene G.']",J Infect Dis,,,True
9b49622e8c16b0e941616d09e9ccdcfbc5d5ff0c,PMC,Graft-vs-tumor effect in patients with advanced nasopharyngeal cancer treated with nonmyeloablative allogeneic PBSC transplantation,http://dx.doi.org/10.1038/bmt.2010.161,PMC3072519,20661236,CC BY-NC-ND,"While nonmyeloablative peripheral blood stem cell transplantation (NST) has shown efficacy against several solid tumors, it is untested in nasopharyngeal cancer (NPC). In a phase II clinical trial, 21 patients with pretreated metastatic NPC underwent NST with sibling PBSC allografts, using CY conditioning, thymic irradiation and in vivo T-cell depletion with thymoglobulin. Stable lymphohematopoietic chimerism was achieved in most patients and prophylactic CYA was tapered at a median of day +30. Seven patients (33%) showed partial response and three (14%) achieved stable disease. Four patients were alive at 2 years and three showed prolonged disease control of 344, 525 and 550 days. With a median follow-up of 209 (4–1147) days, the median PFS was 100 days (95% confidence interval (CI), 66–128 days), and median OS was 209 days (95% CI, 128–236 days). Patients with chronic GVHD had better survival—median OS 426 days (95% CI, 194–NE days) vs 143 days (95% CI, 114–226 days) (P=0.010). Thus, NST may induce meaningful clinical responses in patients with advanced NPC.",2011 Apr 26,"['Toh, H C', 'Chia, W K', 'Sun, L', 'Thng, C H', 'Soe, Y', 'Phoon, Y P', 'Yap, S P', 'Lim, W T', 'Tai, W M', 'Hee, S W', 'Tan, S H', 'Leong, S S', 'Tan, E H']",Bone Marrow Transplant,,,True
3c0c493a037dacafd2eda2e37518e0f0dff7955f,PMC,2009 H1N1 Influenza and Experience in Three Critical Care Units,,PMC3074093,21487571,CC BY-NC-ND,"Aim: We describe futures of ICU admission, demographic characteristics, treatment and outcome for critically ill patients with laboratory-confirmed and suspected infection with the H1N1 virus admitted to the three different critical care departments in Turkey. Methods: Retrospective study of critically ill patients with 2009 influenza A(H1N1) at ICU. Demographic data, symptoms, comorbid conditions, and clinical outcomes were collected using a case report form. Results: Critical illness occurred in 61 patients admitted to an ICU with confirmed (n=45) or probable and suspected 2009 influenza A(H1N1). Patients were young (mean, 41.5 years), were female (54%). Fifty-six patients, required mechanical ventilation (14 invasive, 27 noninvasive, 15 both) during the course of ICU. On admission, mean APACHE II score was 18.7±6.3 and median PaO(2)/FIO(2) was 127.9±70.4. 31 patients (50.8%) was die. There were no significant differences in baseline PaO(2)/FIO(2 )and ventilation strategies between survivors and nonsurvivors. Patients who survived were more likely to have NIMV use at the time of admission to the ICU. Conclusion: Critical illness from 2009 influenza A(H1N1) in ICU predominantly affects young patients with little major comorbidity and had a high case-fatality rate. NIMV could be used in 2009 influenza A (H1N1) infection-related hypoxemic respiratory failure.",2011 Apr 7,"['Teke, Turgut', 'Coskun, Ramazan', 'Sungur, Murat', 'Guven, Muhammed', 'Bekci, Taha T', 'Maden, Emin', 'Alp, Emine', 'Doganay, Mehmet', 'Erayman, Ibrahim', 'Uzun, Kursat']",Int J Med Sci,,,True
782f0ba982d2370ea1a79af73ac66052cd4ad504,PMC,Endogenous ribosomal frameshift signals operate as mRNA destabilizing elements through at least two molecular pathways in yeast,http://dx.doi.org/10.1093/nar/gkq1220,PMC3074144,21109528,CC BY-NC,"Although first discovered in viruses, previous studies have identified operational −1 ribosomal frameshifting (−1 RF) signals in eukaryotic genomic sequences, and suggested a role in mRNA stability. Here, four yeast −1 RF signals are shown to promote significant mRNA destabilization through the nonsense mediated mRNA decay pathway (NMD), and genetic evidence is presented suggesting that they may also operate through the no-go decay pathway (NGD) as well. Yeast EST2 mRNA is highly unstable and contains up to five −1 RF signals. Ablation of the −1 RF signals or of NMD stabilizes this mRNA, and changes in −1 RF efficiency have opposing effects on the steady-state abundance of the EST2 mRNA. These results demonstrate that endogenous −1 RF signals function as mRNA destabilizing elements through at least two molecular pathways in yeast. Consistent with current evolutionary theory, phylogenetic analyses suggest that −1 RF signals are rapidly evolving cis-acting regulatory elements. Identification of high confidence −1 RF signals in ∼10% of genes in all eukaryotic genomes surveyed suggests that −1 RF is a broadly used post-transcriptional regulator of gene expression.",2011 Apr 24,"['Belew, Ashton T.', 'Advani, Vivek M.', 'Dinman, Jonathan D.']",Nucleic Acids Res,,,True
f1fbaa6b9702cdbee92953ef723ea74dd2d013aa,PMC,Endogenous ribosomal frameshift signals operate as mRNA destabilizing elements through at least two molecular pathways in yeast,http://dx.doi.org/10.1093/nar/gkq1220,PMC3074144,21109528,CC BY-NC,"Although first discovered in viruses, previous studies have identified operational −1 ribosomal frameshifting (−1 RF) signals in eukaryotic genomic sequences, and suggested a role in mRNA stability. Here, four yeast −1 RF signals are shown to promote significant mRNA destabilization through the nonsense mediated mRNA decay pathway (NMD), and genetic evidence is presented suggesting that they may also operate through the no-go decay pathway (NGD) as well. Yeast EST2 mRNA is highly unstable and contains up to five −1 RF signals. Ablation of the −1 RF signals or of NMD stabilizes this mRNA, and changes in −1 RF efficiency have opposing effects on the steady-state abundance of the EST2 mRNA. These results demonstrate that endogenous −1 RF signals function as mRNA destabilizing elements through at least two molecular pathways in yeast. Consistent with current evolutionary theory, phylogenetic analyses suggest that −1 RF signals are rapidly evolving cis-acting regulatory elements. Identification of high confidence −1 RF signals in ∼10% of genes in all eukaryotic genomes surveyed suggests that −1 RF is a broadly used post-transcriptional regulator of gene expression.",2011 Apr 24,"['Belew, Ashton T.', 'Advani, Vivek M.', 'Dinman, Jonathan D.']",Nucleic Acids Res,,,False
724a937a58d4217e5d5cc6d1d1e438a5b5b35d6e,PMC,Analysis of the Korean Emergency Department Syndromic Surveillance System: Mass Type Acute Diarrheal Syndrome,http://dx.doi.org/10.4258/hir.2010.16.3.177,PMC3089857,21818437,CC BY-NC,"OBJECTIVES: This study was designed to compare the data from the emergency department syndromic surveillance system of Korea in detection and reporting of acute diarrheal syndrome (mass type) with the data from the Korea Food and Drug Administration. And to offer fundamental materials for making improvements in current surveillance system was our purpose. METHODS: A study was conducted by reviewing the number of cases reported as acute diarrheal syndrome (mass type) from the Korean Center for Disease Control and Prevention between June, 2002 and July, 2008. And the data were compared with the number of mass food poisoning cases during the same period, reported from the Korea Food and Drug Administration. The difference between two groups was measured and their transitions were compared. RESULTS: The emergency department syndromic surveillance system's reports of the numbers of acute diarrheal syndrome (mass type) cases were different from the transition of mass food poisonings, reported by the Korea Food and Drug Administration. Their reports were not accurate and they could not follow the trends of increase in mass food poisonings since 2002. CONCLUSIONS: Current problems in the emergency department syndromic surveillance system in Korea are mostly related to inaccuracies of daily data reporting system. Manual data input by the reporters could play a big role in such inaccuracies. There need to be improvements in the ways of reporting data, such as automated information transport system linking electronic medical record.",2010 Sep 30,"['Ahn, Shin', 'Lee, Jae Ho', 'Kim, Won', 'Lim, Kyung Soo']",Healthc Inform Res,,,True
13f055e666f5a05c1f18856409f9b8f4ac4ae4ce,PMC,Mouse LSECtin as a model for a human Ebola virus receptor,http://dx.doi.org/10.1093/glycob/cwr008,PMC3091528,21257728,CC BY-NC,"The biochemical properties of mouse LSECtin, a glycan-binding receptor that is a member of the C-type lectin family found on sinusoidal endothelial cells, have been investigated. The C-type carbohydrate-recognition domain of mouse LSECtin, expressed in bacteria, has been used in solid-phase binding assays, and a tetramerized form has been used to probe a glycan array. In spite of sequence differences near the glycan-binding sites, the mouse receptor closely mimics the properties of the human receptor, showing high affinity binding to glycans bearing terminal GlcNAcβ1-2Man motifs. Site-directed mutagenesis has been used to confirm that residues near the binding site that differ between the human and the mouse proteins do not affect this binding specificity. Mouse and human LSECtin have been shown to bind Ebola virus glycoprotein with equivalent affinities, and the GlcNAcβ1-2Man disaccharide has been demonstrated to be an effective inhibitor of this interaction. These studies provide a basis for using mouse LSECtin, and knockout mice lacking this receptor, to model the biological properties of the human receptor.",2011 Jun 21,"['Pipirou, Zoi', 'Powlesland, Alex S', 'Steffen, Imke', 'Pöhlmann, Stefan', 'Taylor, Maureen E', 'Drickamer, Kurt']",Glycobiology,,,True
92e14fff3e37477102149550fc8f3ff9d5ffc6f6,PMC,HIV-1 Modulates the tRNA Pool to Improve Translation Efficiency,http://dx.doi.org/10.1093/molbev/msr005,PMC3098512,21216840,CC BY-NC,"Despite its poorly adapted codon usage, HIV-1 replicates and is expressed extremely well in human host cells. HIV-1 has recently been shown to package non-lysyl transfer RNAs (tRNAs) in addition to the tRNA(Lys) needed for priming reverse transcription and integration of the HIV-1 genome. By comparing the codon usage of HIV-1 genes with that of its human host, we found that tRNAs decoding codons that are highly used by HIV-1 but avoided by its host are overrepresented in HIV-1 virions. In particular, tRNAs decoding A-ending codons, required for the expression of HIV's A-rich genome, are highly enriched. Because the affinity of Gag-Pol for all tRNAs is nonspecific, HIV packaging is most likely passive and reflects the tRNA pool at the time of viral particle formation. Codon usage of HIV-1 early genes is similar to that of highly expressed host genes, but codon usage of HIV-1 late genes was better adapted to the selectively enriched tRNA pool, suggesting that alterations in the tRNA pool are induced late in viral infection. If HIV-1 genes are adapting to an altered tRNA pool, codon adaptation of HIV-1 may be better than previously thought.",2011 Jun 7,"['van Weringh, Anna', 'Ragonnet-Cronin, Manon', 'Pranckeviciene, Erinija', 'Pavon-Eternod, Mariana', 'Kleiman, Lawrence', 'Xia, Xuhua']",Mol Biol Evol,,,True
3062cebd70447841d68c48fe83f0eb51b07a761d,PMC,Lectin Switching During Dengue Virus Infection,http://dx.doi.org/10.1093/infdis/jir173,PMC3100511,21606536,CC BY-NC,"Dengue virus receptors are relatively poorly characterized, but there has been recent interest in 2 C-type lectin molecules, dendritic cell–specific intercellular adhesion molecule 3 (ICAM-3)–grabbing nonintegrin (DC-SIGN) and its close homologue liver/lymph node–specific ICAM-3–grabbing integrin (L-SIGN), which can both bind dengue and promote infection. In this report we have studied the interaction of dengue viruses produced in insect cells, tumor cell lines, and primary human dendritic cells (DCs) with DC-SIGN and L-SIGN. Virus produced in primary DCs is unable to interact with DC-SIGN but remains infectious for L-SIGN–expressing cells. Skin-resident DCs may thus be a site of initial infection by insect-produced virus, but DCs will likely not participate in large-scale virus replication during dengue infection. These results reveal that differential glycosylation of dengue virus envelope protein is highly dependent on cell state and suggest that studies of virus tropism using virus prepared in insect cells or tumor cell lines should be interpreted with caution.",2011 Jun 15,"['Dejnirattisai, Wanwisa', 'Webb, Andrew I.', 'Chan, Vera', 'Jumnainsong, Amonrat', 'Davidson, Andrew', 'Mongkolsapaya, Juthathip', 'Screaton, Gavin']",J Infect Dis,,,True
9665e16e8fd0e3198298f64f70cc9180d1cea36a,PMC,Detection and Identification of Common Food-Borne Viruses with a Tiling Microarray,http://dx.doi.org/10.2174/1874357901105010052,PMC3109525,21660190,CC BY-NC,"Microarray hybridization based identification of viral genotypes is increasingly assuming importance due to outbreaks of multiple pathogenic viruses affecting humans causing wide-spread morbidity and mortality. Surprisingly, microarray based identification of food-borne viruses, one of the largest groups of pathogenic viruses, causing more than 1.5 billion infections world-wide every year, has lagged behind. Cell-culture techniques are either unavailable or time consuming for routine application. Consequently, current detection methods for these pathogens largely depend on polymerase chain reaction (PCR) based techniques, generally requiring an investigator to preselect the target virus of interest. Here we describe the first attempt to use the microarray as an identification tool for these viruses. We have developed methodology to synthesize targets for virus identification without using PCR, making the process genuinely sequence independent. We show here that a tiling microarray can simultaneously detect and identify the genotype and strain of common food-borne viruses in a single experiment.",2011 May 16,"['Chen, Haifeng', 'Mammel, Mark', 'Kulka, Mike', 'Patel, Isha', 'Jackson, Scott', 'Goswami, Biswendu B.']",Open Virol J,,,True
d45f0042fd65b1a24873bab4fb027c22d122d3d3,PMC,An Insect Nidovirus Emerging from a Primary Tropical Rainforest,http://dx.doi.org/10.1128/mBio.00077-11,PMC3111606,21673192,CC BY-NC-SA,"Tropical rainforests show the highest level of terrestrial biodiversity and may be an important contributor to microbial diversity. Exploitation of these ecosystems may foster the emergence of novel pathogens. We report the discovery of the first insect-associated nidovirus, tentatively named Cavally virus (CAVV). CAVV was found with a prevalence of 9.3% during a survey of mosquito-associated viruses along an anthropogenic disturbance gradient in Côte d’Ivoire. Analysis of habitat-specific virus diversity and ancestral state reconstruction demonstrated an origin of CAVV in a pristine rainforest with subsequent spread into agriculture and human settlements. Virus extension from the forest was associated with a decrease in virus diversity (P < 0.01) and an increase in virus prevalence (P < 0.00001). CAVV is an enveloped virus with large surface projections. The RNA genome comprises 20,108 nucleotides with seven major open reading frames (ORFs). ORF1a and -1b encode two large proteins that share essential features with phylogenetically higher representatives of the order Nidovirales, including the families Coronavirinae and Torovirinae, but also with families in a basal phylogenetic relationship, including the families Roniviridae and Arteriviridae. Genetic markers uniquely conserved in nidoviruses, such as an endoribonuclease- and helicase-associated zinc-binding domain, are conserved in CAVV. ORF2a and -2b are predicted to code for structural proteins S and N, respectively, while ORF3a and -3b encode proteins with membrane-spanning regions. CAVV produces three subgenomic mRNAs with 5′ leader sequences (of different lengths) derived from the 5′ end of the genome. This novel cluster of mosquito-associated nidoviruses is likely to represent a novel family within the order Nidovirales.",2011 Jun 14,"['Zirkel, Florian', 'Kurth, Andreas', 'Quan, Phenix-Lan', 'Briese, Thomas', 'Ellerbrok, Heinz', 'Pauli, Georg', 'Leendertz, Fabian H.', 'Lipkin, W. Ian', 'Ziebuhr, John', 'Drosten, Christian', 'Junglen, Sandra']",mBio,,,True
64077bbb45ff272c7c89aa39e0da9d251ecd08fa,PMC,An Insect Nidovirus Emerging from a Primary Tropical Rainforest,http://dx.doi.org/10.1128/mBio.00077-11,PMC3111606,21673192,CC BY-NC-SA,"Tropical rainforests show the highest level of terrestrial biodiversity and may be an important contributor to microbial diversity. Exploitation of these ecosystems may foster the emergence of novel pathogens. We report the discovery of the first insect-associated nidovirus, tentatively named Cavally virus (CAVV). CAVV was found with a prevalence of 9.3% during a survey of mosquito-associated viruses along an anthropogenic disturbance gradient in Côte d’Ivoire. Analysis of habitat-specific virus diversity and ancestral state reconstruction demonstrated an origin of CAVV in a pristine rainforest with subsequent spread into agriculture and human settlements. Virus extension from the forest was associated with a decrease in virus diversity (P < 0.01) and an increase in virus prevalence (P < 0.00001). CAVV is an enveloped virus with large surface projections. The RNA genome comprises 20,108 nucleotides with seven major open reading frames (ORFs). ORF1a and -1b encode two large proteins that share essential features with phylogenetically higher representatives of the order Nidovirales, including the families Coronavirinae and Torovirinae, but also with families in a basal phylogenetic relationship, including the families Roniviridae and Arteriviridae. Genetic markers uniquely conserved in nidoviruses, such as an endoribonuclease- and helicase-associated zinc-binding domain, are conserved in CAVV. ORF2a and -2b are predicted to code for structural proteins S and N, respectively, while ORF3a and -3b encode proteins with membrane-spanning regions. CAVV produces three subgenomic mRNAs with 5′ leader sequences (of different lengths) derived from the 5′ end of the genome. This novel cluster of mosquito-associated nidoviruses is likely to represent a novel family within the order Nidovirales.",2011 Jun 14,"['Zirkel, Florian', 'Kurth, Andreas', 'Quan, Phenix-Lan', 'Briese, Thomas', 'Ellerbrok, Heinz', 'Pauli, Georg', 'Leendertz, Fabian H.', 'Lipkin, W. Ian', 'Ziebuhr, John', 'Drosten, Christian', 'Junglen, Sandra']",mBio,,,False
25bf1749d3f9bc914e8ac243006b332db27e4671,PMC,An Insect Nidovirus Emerging from a Primary Tropical Rainforest,http://dx.doi.org/10.1128/mBio.00077-11,PMC3111606,21673192,CC BY-NC-SA,"Tropical rainforests show the highest level of terrestrial biodiversity and may be an important contributor to microbial diversity. Exploitation of these ecosystems may foster the emergence of novel pathogens. We report the discovery of the first insect-associated nidovirus, tentatively named Cavally virus (CAVV). CAVV was found with a prevalence of 9.3% during a survey of mosquito-associated viruses along an anthropogenic disturbance gradient in Côte d’Ivoire. Analysis of habitat-specific virus diversity and ancestral state reconstruction demonstrated an origin of CAVV in a pristine rainforest with subsequent spread into agriculture and human settlements. Virus extension from the forest was associated with a decrease in virus diversity (P < 0.01) and an increase in virus prevalence (P < 0.00001). CAVV is an enveloped virus with large surface projections. The RNA genome comprises 20,108 nucleotides with seven major open reading frames (ORFs). ORF1a and -1b encode two large proteins that share essential features with phylogenetically higher representatives of the order Nidovirales, including the families Coronavirinae and Torovirinae, but also with families in a basal phylogenetic relationship, including the families Roniviridae and Arteriviridae. Genetic markers uniquely conserved in nidoviruses, such as an endoribonuclease- and helicase-associated zinc-binding domain, are conserved in CAVV. ORF2a and -2b are predicted to code for structural proteins S and N, respectively, while ORF3a and -3b encode proteins with membrane-spanning regions. CAVV produces three subgenomic mRNAs with 5′ leader sequences (of different lengths) derived from the 5′ end of the genome. This novel cluster of mosquito-associated nidoviruses is likely to represent a novel family within the order Nidovirales.",2011 Jun 14,"['Zirkel, Florian', 'Kurth, Andreas', 'Quan, Phenix-Lan', 'Briese, Thomas', 'Ellerbrok, Heinz', 'Pauli, Georg', 'Leendertz, Fabian H.', 'Lipkin, W. Ian', 'Ziebuhr, John', 'Drosten, Christian', 'Junglen, Sandra']",mBio,,,False
7627a1c7020be9b495eb7345fb3867484d618d78,PMC,"Past, present and future: experiences and lessons from telehealth projects",,PMC3113223,21673948,CC BY-SA,"Information communications technology has been a focus of the work of the International Development Research Centre (IDRC) since 1970, when this organization was formed in Canada with the goal of helping to improve the health of people in developing countries (http://www.idrc.ca). In this article, we focus on the field of telemedicine in developing countries and its role in improving health, using examples from the experience of the IDRC.",2007 Dec 4,"['Elder, Laurent', 'Clarke, Michael']",Open Med,,,True
dd286ebc387ae032200bd0b1c1d4f659e278d7b0,PMC,A novel immunity system for bacterial nucleic acid degrading toxins and its recruitment in various eukaryotic and DNA viral systems,http://dx.doi.org/10.1093/nar/gkr036,PMC3113570,21306995,CC BY-NC,"The use of nucleases as toxins for defense, offense or addiction of selfish elements is widely encountered across all life forms. Using sensitive sequence profile analysis methods, we characterize a novel superfamily (the SUKH superfamily) that unites a diverse group of proteins including Smi1/Knr4, PGs2, FBXO3, SKIP16, Syd, herpesviral US22, IRS1 and TRS1, and their bacterial homologs. Using contextual analysis we present evidence that the bacterial members of this superfamily are potential immunity proteins for a variety of toxin systems that also include the recently characterized contact-dependent inhibition (CDI) systems of proteobacteria. By analyzing the toxin proteins encoded in the neighborhood of the SUKH superfamily we predict that they possess domains belonging to diverse nuclease and nucleic acid deaminase families. These include at least eight distinct types of DNases belonging to HNH/EndoVII- and restriction endonuclease-fold, and RNases of the EndoU-like and colicin E3-like cytotoxic RNases-folds. The N-terminal domains of these toxins indicate that they are extruded by several distinct secretory mechanisms such as the two-partner system (shared with the CDI systems) in proteobacteria, ESAT-6/WXG-like ATP-dependent secretory systems in Gram-positive bacteria and the conventional Sec-dependent system in several bacterial lineages. The hedgehog-intein domain might also release a subset of toxic nuclease domains through auto-proteolytic action. Unlike classical colicin-like nuclease toxins, the overwhelming majority of toxin systems with the SUKH superfamily is chromosomally encoded and appears to have diversified through a recombination process combining different C-terminal nuclease domains to N-terminal secretion-related domains. Across the bacterial superkingdom these systems might participate in discriminating `self’ or kin from `non-self’ or non-kin strains. Using structural analysis we demonstrate that the SUKH domain possesses a versatile scaffold that can be used to bind a wide range of protein partners. In eukaryotes it appears to have been recruited as an adaptor to regulate modification of proteins by ubiquitination or polyglutamylation. Similarly, another widespread immunity protein from these toxin systems, namely the suppressor of fused (SuFu) superfamily has been recruited for comparable roles in eukaryotes. In animal DNA viruses, such as herpesviruses, poxviruses, iridoviruses and adenoviruses, the ability of the SUKH domain to bind diverse targets has been deployed to counter diverse anti-viral responses by interacting with specific host proteins.",2011 Jun 8,"['Zhang, Dapeng', 'Iyer, Lakshminarayan M.', 'Aravind, L.']",Nucleic Acids Res,,,True
ca8b14f351edca29473646f4bb9669c3ad03500c,PMC,BAG3: a multifaceted protein that regulates major cell pathways,http://dx.doi.org/10.1038/cddis.2011.24,PMC3122056,21472004,CC BY-NC-ND,"Bcl2-associated athanogene 3 (BAG3) protein is a member of BAG family of co-chaperones that interacts with the ATPase domain of the heat shock protein (Hsp) 70 through BAG domain (110–124 amino acids). BAG3 is the only member of the family to be induced by stressful stimuli, mainly through the activity of heat shock factor 1 on bag3 gene promoter. In addition to the BAG domain, BAG3 contains also a WW domain and a proline-rich (PXXP) repeat, that mediate binding to partners different from Hsp70. These multifaceted interactions underlie BAG3 ability to modulate major biological processes, that is, apoptosis, development, cytoskeleton organization and autophagy, thereby mediating cell adaptive responses to stressful stimuli. In normal cells, BAG3 is constitutively present in a very few cell types, including cardiomyocytes and skeletal muscle cells, in which the protein appears to contribute to cell resistance to mechanical stress. A growing body of evidence indicate that BAG3 is instead expressed in several tumor types. In different tumor contexts, BAG3 protein was reported to sustain cell survival, resistance to therapy, and/or motility and metastatization. In some tumor types, down-modulation of BAG3 levels was shown, as a proof-of-principle, to inhibit neoplastic cell growth in animal models. This review attempts to outline the emerging mechanisms that can underlie some of the biological activities of the protein, focusing on implications in tumor progression.",2011 Apr 7,"['Rosati, A', 'Graziano, V', 'De Laurenzi, V', 'Pascale, M', 'Turco, M C']",Cell Death Dis,,,True
92ae74cf9e28a780d600c36da4b09591b65c87cd,PMC,Gene Expression Profile during Chondrogenesis in Human Bone Marrow derived Mesenchymal Stem Cells using a cDNA Microarray,http://dx.doi.org/10.3346/jkms.2011.26.7.851,PMC3124712,21738335,CC BY-NC,"Mesenchymal stem cells (MSCs) have the capacity to proliferate and differentiate into multiple connective tissue lineages, which include cartilage, bone, and fat. Cartilage differentiation and chondrocyte maturation are required for normal skeletal development, but the intracellular pathways regulating this process remain largely unclear. This study was designed to identify novel genes that might help clarify the molecular mechanisms of chondrogenesis. Chondrogenesis was induced by culturing human bone marrow (BM) derived MSCs in micromass pellets in the presence of defined medium for 3, 7, 14 or 21 days. Several genes regulated during chondrogenesis were then identified by reverse transcriptase-polymerase chain reaction (RT-PCR). Using an ABI microarray system, we determined the differential gene expression profiles of differentiated chondrocytes and BM-MSCs. Normalization of this data resulted in the identification of 1,486 differentially expressed genes. To verify gene expression profiles determined by microarray analysis, the expression levels of 10 genes with high fold changes were confirmed by RT-PCR. Gene expression patterns of 9 genes (Hrad6B, annexinA2, BMP-7, contactin-1, peroxiredoxin-1, heat shock transcription factor-2, synaptotagmin IV, serotonin receptor-7, Axl) in RT-PCR were similar to the microarray gene expression patterns. These findings provide novel information concerning genes involved in the chondrogenesis of human BM-MSCs.",2011 Jul 20,"['Yoo, Hyun Jung', 'Yoon, Sung Soo', 'Park, Seon Yang', 'Lee, Eun Young', 'Lee, Eun Bong', 'Kim, Ju Han', 'Song, Yeong Wook']",J Korean Med Sci,,,True
3d86ddb1f87053b373d42baadaba6a449fb22fa4,PMC,Human Bocavirus in Patients with Respiratory Tract Infection,http://dx.doi.org/10.3343/kjlm.2011.31.3.179,PMC3129349,21779192,CC BY-NC,"BACKGROUND: Human bocavirus (HBoV) is a newly identified viral pathogen, and its clinical epidemiology and significance in respiratory infections have not yet been completely elucidated. We investigated the prevalence of HBoV infection and the association between viral (HBoV) load and clinical features of the infection in patients of all age-groups. METHODS: Nasopharyngeal aspirates from patients with symptoms of respiratory infection were tested for presence of HBoV by using real-time polymerase chain reaction. HBoV-positive patients were categorized into low- and high-viral-load groups using 1.0×10(6) copies/mL as the threshold value of viral load. RESULTS: Detection rate of HBoV was 4.8% (N=93) in a total of 1,926 samples with peak incidence of infection being observed in patients aged 6-12 months. HBoV infection was more frequently observed in young children, especially, in children aged less than 5 yr, and the HBoV load decreased with increase in age. HBoV was codetected with other respiratory viruses in 17 (18.3%) of the 93 HBoV-positive patients and 15 patients (88.2%) belonged to the low-viral-load group. Patients infected with HBoV alone showed a higher viral load than those patients in whom HBoV was codetected with other respiratory viruses (median load, 3.78×10(5) copies/mL vs. 1.94×10(4) copies/mL, P=0.014). Higher pulse rate (P=0.007) and respiratory rate (P=0.021) were observed in patients with a high-viral-load. CONCLUSIONS: Our results suggest that HBoV may be the causative agent of respiratory infection in the high-viral-load group.",2011 Jul 28,"['Kim, Jang Su', 'Lim, Chae Seung', 'Kim, Young Kee', 'Lee, Kap No', 'Lee, Chang Kyu']",Korean J Lab Med,,,True
c0f102738445b0a4c2af4323fe69d319d9e09eda,PMC,Seasonal distribution of active systemic lupus erythematosus and its correlation with meteorological factors,http://dx.doi.org/10.1590/S1807-59322011000600015,PMC3129944,21808867,CC BY-NC,"OBJECTIVE: To explore the characteristics of seasonal distribution of active systemic lupus erythematosus (SLE) and the influences of meteorological factors including temperature and humidity on active systemic lupus erythematosus. METHODS: The characteristics of seasonal distribution of active SLE and its correlation with meteorological factors were retrospectively analyzed in 640 patients living in the city of Zhanjiang, China and had active SLE between January 1997 and December 2006. RESULTS: In winter, when there are weaker ultraviolet (UV) rays, the ratio of patients with active SLE to total inpatients was 3.89 ‰, which is significantly higher than in other seasons with stronger UV rays, including 2.17 ‰ in spring, 1.87 ‰ in summer and 2.12 ‰ in autumn. The number of patients with active SLE had significant negative correlation with mean temperature and was not significantly related to mean humidity. CONCLUSION: Active SLE has the characteristics of seasonal distribution and is associated with temperature. The mechanism remains to be further studied.",2011 Jun,"['Zhang, Hua-Li', 'Xu, Shi-Chao', 'Tang, De-Shen', 'Liang, Dong', 'Liu, Hua-Feng*']",Clinics (Sao Paulo),,,True
f5b032ddcc2c69fa564eec3ac027060064d7b255,PMC,New Respiratory Viruses and the Elderly,http://dx.doi.org/10.2174/1874306401105010061,PMC3134957,21760867,CC BY-NC,"The diagnostics of respiratory viral infections has improved markedly during the last 15 years with the development of PCR techniques. Since 1997, several new respiratory viruses and their subgroups have been discovered: influenza A viruses H5N1 and H1N1, human metapneumovirus, coronaviruses SARS, NL63 and HKU1, human bocavirus, human rhinoviruses C and D and potential respiratory pathogens, the KI and WU polyomaviruses and the torque teno virus. The detection of previously known viruses has also improved. Currently, a viral cause of respiratory illness is almost exclusively identifiable in children, but in the elderly, the detection rates of a viral etiology are below 40%, and this holds also true for exacerbations of chronic respiratory illnesses. The new viruses cause respiratory symptoms like the common cold, cough, bronchitis, bronchiolitis, exacerbations of asthma and chronic obstructive pulmonary disease and pneumonia. Acute respiratory failure may occur. These viruses are distributed throughout the globe and affect people of all ages. Data regarding these viruses and the elderly are scarce. This review introduces these new viruses and reviews their clinical significance, especially with regard to the elderly population.",2011 Jul 6,"['Jartti, Laura', 'Langen, Henriikka', 'Söderlund-Venermo, Maria', 'Vuorinen, Tytti', 'Ruuskanen, Olli', 'Jartti, Tuomas']",Open Respir Med J,,,True
c11d970819187c52f9f81d870637aec8779b05d3,PMC,The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a γδ T cell population in humanized mice,http://dx.doi.org/10.1084/jem.20110226,PMC3135369,21708931,CC BY-NC-SA,"There are few antiviral drugs for treating influenza, and the emergence of antiviral resistance has further limited the available therapeutic options. Furthermore, antivirals are not invariably effective in severe influenza, such as that caused by H5N1 viruses. Thus, there is an urgent need to develop alternative therapeutic strategies. Here, we show that human Vγ9Vδ2 T cells expanded by the aminobisphosphonate pamidronate (PAM) kill influenza virus–infected cells and inhibit viral replication in vitro. In Rag2(−/−)γc(−/−) immunodeficient mice reconstituted with human peripheral mononuclear cells (huPBMCs), PAM reduces disease severity and mortality caused by human seasonal H1N1 and avian H5N1 influenza virus, and controls the lung inflammation and viral replication. PAM has no such effects in influenza virus–infected Rag2(−/−)γc(−/−) mice reconstituted with Vγ9Vδ2 T cell–depleted huPBMCs. Our study provides proof-of-concept of a novel therapeutic strategy for treating influenza by targeting the host rather than the virus, thereby reducing the opportunity for the emergence of drug-resistant viruses. As PAM has been commonly used to treat osteoporosis and Paget’s disease, this new application of an old drug potentially offers a safe and readily available option for treating influenza.",2011 Jul 4,"['Tu, Wenwei', 'Zheng, Jian', 'Liu, Yinping', 'Sia, Sin Fun', 'Liu, Ming', 'Qin, Gang', 'Ng, Iris H.Y.', 'Xiang, Zheng', 'Lam, Kwok-Tai', 'Peiris, J.S. Malik', 'Lau, Yu-Lung']",J Exp Med,,,True
e68ff81b1cbbfd6bb525f60a9efdfacf899dabd5,PMC,The fertility quality of life (FertiQoL) tool: development and general psychometric properties(†),http://dx.doi.org/10.1093/humrep/der171,PMC3137391,21665875,CC BY-NC,"BACKGROUND: To develop the first international instrument to measure fertility quality of life (FertiQoL) in men and women experiencing fertility problems, to evaluate the preliminary psychometric properties of this new tool and to translate FertiQoL into multiple languages. METHOD: We conducted a survey, both online and in fertility clinics in USA, Australia/New Zealand, Canada and UK. A total of 1414 people with fertility problems participated. The main outcome measure was the FertiQoL tool. RESULTS: FertiQoL consists of 36 items that assess core (24 items) and treatment-related quality of life (QoL) (10 items) and overall life and physical health (2 items). Cronbach reliability statistics for the Core and Treatment FertiQoL (and subscales) were satisfactory and in the range of 0.72 and 0.92. Sensitivity analyses showed that FertiQoL detected expected relations between QoL and gender, parity and support-seeking. FertiQoL was translated into 20 languages by the same translation team with each translation verified by local bilingual fertility experts. CONCLUSIONS: FertiQoL is a reliable measure of the impact of fertility problems and its treatment on QoL. Future research should establish its use in cross-cultural research and clinical work.",2011 Aug 10,"['Boivin, Jacky', 'Takefman, Janet', 'Braverman, Andrea']",Hum Reprod,,,True
9547b74fb56cd1288d9af6facbd337148cf45895,PMC,"Demographic, etiological, and histological pulmonary analysis of patients with acute respiratory failure: a study of 19 years of autopsies",http://dx.doi.org/10.1590/S1807-59322011000700012,PMC3148463,21876973,CC BY-NC,"INTRODUCTION: Acute respiratory failure has been one of the most important causes of death in intensive care units, and certain aspects of its pulmonary pathology are currently unknown. OBJECTIVES: The objective was to describe the demographic data, etiology, and pulmonary histopathological findings of different diseases in the autopsies of patients with acute respiratory failure. METHOD: Autopsies of 4,710 patients with acute respiratory failure from 1990 to 2008 were reviewed, and the following data were obtained: age, sex, and major associated diseases. The pulmonary histopathology was categorized as diffuse alveolar damage, pulmonary edema, alveolar hemorrhage, and lymphoplasmacytic interstitial pneumonia. The odds ratio of the concordance between the major associated diseases and specific autopsy findings was calculated using logistic regression. RESULTS: Bacterial bronchopneumonia was present in 33.9% of the cases and cancer in 28.1%. The pulmonary histopathology showed diffuse alveolar damage in 40.7% (1,917) of the cases. A multivariate analysis showed a significant and powerful association between diffuse alveolar damage and bronchopneumonia, HIV/AIDS, sepsis, and septic shock, between liver cirrhosis and pulmonary embolism, between pulmonary edema and acute myocardial infarction, between dilated cardiomyopathy and cancer, between alveolar hemorrhage and bronchopneumonia and pulmonary embolism, and between lymphoplasmacytic interstitial pneumonia and HIV/AIDS and liver cirrhosis. CONCLUSIONS: Bronchopneumonia was the most common diagnosis in these cases. The most prevalent pulmonary histopathological pattern was diffuse alveolar damage, which was associated with different inflammatory conditions. Further studies are necessary to elucidate the complete pathophysiological mechanisms involved with each disease and the development of acute respiratory failure.",2011 Jul,"['de Matos Soeiro, Alexandre', 'Ruppert, Aline D', 'Canzian, Mauro', 'Parra, Edwin R', 'Farhat, Cecília', 'Capelozzi, Vera L']",Clinics (Sao Paulo),,,True
13e6c9b0730b53139910cfa6835ae4c460a30851,PMC,IFN-γ– and IL-10–expressing virus epitope-specific Foxp3(+) T reg cells in the central nervous system during encephalomyelitis,http://dx.doi.org/10.1084/jem.20110236,PMC3149215,21746812,CC BY-NC-SA,"Foxp3(+) CD4 regulatory T cells (T reg cells) are important in limiting immunopathology in infections. However, identifying pathogen-specific epitopes targeted by these cells has been elusive. Using MHC class II/peptide tetramers and intracellular cytokine staining, we identify T reg cells recognizing two virus-specific CD4 T cell epitopes in the coronavirus-infected central nervous system as well as naive T cell precursor pools. These T reg cells are detected at the same time as effector T cells (T eff cells) exhibiting the same specificity and can suppress T eff cell proliferation after stimulation with cognate peptide. These virus-specific T reg cells may be especially effective in inhibiting the immune response during the peak of infection, when virus antigen is maximal. Furthermore, these T reg cells express both IL-10 and IFN-γ after peptide stimulation. IFN-γ expression is maintained during both acute and chronic phases of infection. Identification of T reg cell target epitopes by cytokine production is also applicable in autoimmune disease because myelin oligodendrocyte glycoprotein–specific Foxp3(+) T reg cells express IL-10 and IL-17 at the peak of disease in mice with experimental autoimmune encephalomyelitis. These results show that pathogen epitope-specific Foxp3(+) T reg cells can be identified on the basis of cytokine production.",2011 Aug 1,"['Zhao, Jingxian', 'Zhao, Jincun', 'Fett, Craig', 'Trandem, Kathryn', 'Fleming, Erica', 'Perlman, Stanley']",J Exp Med,,,True
c3e846076762b54e33385752eb27e086f6cb8b72,PMC,Type 1 Interferon Induction of Natural Killer Cell Gamma Interferon Production for Defense during Lymphocytic Choriomeningitis Virus Infection,http://dx.doi.org/10.1128/mBio.00169-11,PMC3150756,21828218,CC BY-NC-SA,"Natural killer (NK) cells are equipped to innately produce the cytokine gamma interferon (IFN-γ) in part because they basally express high levels of the signal transducer and activator of transcription 4 (STAT4). Type 1 interferons (IFNs) have the potential to activate STAT4 and promote IFN-γ expression, but concurrent induction of elevated STAT1 negatively regulates access to the pathway. As a consequence, it has been difficult to detect type 1 IFN stimulation of NK cell IFN-γ during viral infections in the presence of STAT1 and to understand the evolutionary advantage for maintaining the pathway. The studies reported here evaluated NK cell responses following infections with lymphocytic choriomeningitis virus (LCMV) in the compartment handling the earliest events after infection, the peritoneal cavity. The production of type 1 IFNs, both IFN-α and IFN-β, was shown to be early and of short duration, peaking at 30 h after challenge. NK cell IFN-γ expression was detected with overlapping kinetics and required activating signals delivered through type 1 IFN receptors and STAT4. It took place under conditions of high STAT4 levels but preceded elevated STAT1 expression in NK cells. The IFN-γ response reduced viral burdens. Interestingly, increases in STAT1 were delayed in NK cells compared to other peritoneal exudate cell (PEC) populations. Taken together, the studies demonstrate a novel mechanism for stimulating IFN-γ production and elucidate a biological role for type 1 IFN access to STAT4 in NK cells.",2011 Aug 9,"['Mack, Ethan A.', 'Kallal, Lara E.', 'Demers, Delia A.', 'Biron, Christine A.']",mBio,,,True
0a64b2c55fc2091358da4f83ac6fdc7701ddb46e,PMC,"A rapid, inexpensive yeast-based dual-fluorescence assay of programmed—1 ribosomal frameshifting for high-throughput screening",http://dx.doi.org/10.1093/nar/gkr382,PMC3152369,21602263,CC BY-NC,"Programmed −1 ribosomal frameshifting (−1 PRF) is a mechanism that directs elongating ribosomes to shift-reading frame by 1 base in the 5′ direction that is utilized by many RNA viruses. Importantly, rates of −1 PRF are fine-tuned by viruses, including Retroviruses, Coronaviruses, Flavivriuses and in two endogenous viruses of the yeast Saccharomyces cerevisiae, to deliver the correct ratios of different viral proteins for efficient replication. Thus, −1 PRF presents a novel target for antiviral therapeutics. The underlying molecular mechanism of −1 PRF is conserved from yeast to mammals, enabling yeast to be used as a logical platform for high-throughput screens. Our understanding of the strengths and pitfalls of assays to monitor −1 PRF have evolved since the initial discovery of −1 PRF. These include controlling for the effects of drugs on protein expression and mRNA stability, as well as minimizing costs and the requirement for multiple processing steps. Here we describe the development of an automated yeast-based dual fluorescence assay of −1 PRF that provides a rapid, inexpensive automated pipeline to screen for compounds that alter rates of −1 PRF which will help to pave the way toward the discovery and development of novel antiviral therapeutics.",2011 Aug 20,"['Rakauskaitė, Rasa', 'Liao, Pei-Yu', 'Rhodin, Michael H. J.', 'Lee, Kelvin', 'Dinman, Jonathan D.']",Nucleic Acids Res,,,True
259f3f6bc30f4fce9f20d4ca222e2d5d04b5377d,PMC,Harnessing the immune system's arsenal: producing human monoclonal antibodies for therapeutics and investigating immune responses,http://dx.doi.org/10.3410/B3-17,PMC3155207,21876728,CC BY-NC,"Monoclonal antibody technology has undergone rapid and innovative reinvention over the last 30 years. Application of these technologies to human samples revealed valuable therapeutic and experimental insights. These technologies, each with their own benefits and flaws, have proven indispensable for immunological research and in our fight to provide new treatments and improved vaccines for infectious disease.",2011 Aug 1,"['Sullivan, Meghan', 'Kaur, Kaval', 'Pauli, Noel', 'Wilson, Patrick C.']",F1000 Biol Rep,,,True
b39580b3bf3af68ed88977c56efdca4d41816b10,PMC,Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo,,PMC3157269,21850204,CC BY-NC-ND,"Porcine reproductive and respiratory syndrome virus (PRRSV) infects mainly the porcine alveolar macrophages (PAMs) and causes porcine reproductive and respiratory syndrome (PRRS). Previous studies have analyzed the global gene expression profiles of lung tissue in vivo and PAMs in vitro following infection with PRRSV, however, transcriptome-wide understanding of the interaction between highly pathogenic PRRSV (HP-PRRSV) and PAMs in vivo has not yet been established. In this study, we employed Affymetrix microarrays to investigate the gene expression patterns of PAMs isolated from Tongcheng piglets (a Chinese indigenous breed) after infection with HP-PRRSV. During the infection, Tongcheng piglets exhibited typical clinical signs, e.g. fever, asthma, coughing, anorexia, lethargy and convulsion, but displayed mild regional lung damage at 5 and 7 dpi. Microarray analysis revealed that HP-PRRSV infection has affected PAMs in expression of the important genes involved in cytoskeleton and exocytosis organization, protein degradation and folding, intracellular calcium and zinc homeostasis. Several potential antiviral strategies might be employed in PAMs, including upregulating IFN-induced genes and increasing intracellular zinc ion concentration. And inhibition of the complement system likely attenuated the lung damage during HP-PRRSV infection. Transcriptomic analysis of PAMs in vivo could lead to a better understanding of the HP-PRRSV-host interaction, and to the identification of novel antiviral therapies and genetic components of swine tolerance/susceptibility to HP-PRRS.",2011 Aug 7,"['Zhou, Ping', 'Zhai, Shanli', 'Zhou, Xiang', 'Lin, Ping', 'Jiang, Tengfei', 'Hu, Xueying', 'Jiang, Yunbo', 'Wu, Bin', 'Zhang, Qingde', 'Xu, Xuewen', 'Li, Jin-ping', 'Liu, Bang']",Int J Biol Sci,,,True
efa709d35a459e7655763486cc6d5ee29aca19a6,PMC,Stimulation of stop codon readthrough: frequent presence of an extended 3′ RNA structural element,http://dx.doi.org/10.1093/nar/gkr224,PMC3159437,21525127,CC BY-NC,"In Sindbis, Venezuelan equine encephalitis and related alphaviruses, the polymerase is translated as a fusion with other non-structural proteins via readthrough of a UGA stop codon. Surprisingly, earlier work reported that the signal for efficient readthrough comprises a single cytidine residue 3′-adjacent to the UGA. However, analysis of variability at synonymous sites revealed strikingly enhanced conservation within the ∼150 nt 3′-adjacent to the UGA, and RNA folding algorithms revealed the potential for a phylogenetically conserved stem–loop structure in the same region. Mutational analysis of the predicted structure demonstrated that the stem–loop increases readthrough by up to 10-fold. The same computational analysis indicated that similar RNA structures are likely to be relevant to readthrough in certain plant virus genera, notably Furovirus, Pomovirus, Tobravirus, Pecluvirus and Benyvirus, as well as the Drosophilia gene kelch. These results suggest that 3′ RNA stimulatory structures feature in a much larger proportion of readthrough cases than previously anticipated, and provide a new criterion for assessing the large number of cellular readthrough candidates that are currently being revealed by comparative sequence analysis.",2011 Aug 27,"['Firth, Andrew E.', 'Wills, Norma M.', 'Gesteland, Raymond F.', 'Atkins, John F.']",Nucleic Acids Res,,,True
3430ff3e67a0d859261f21a84ff374f83374033f,PMC,Stimulation of stop codon readthrough: frequent presence of an extended 3′ RNA structural element,http://dx.doi.org/10.1093/nar/gkr224,PMC3159437,21525127,CC BY-NC,"In Sindbis, Venezuelan equine encephalitis and related alphaviruses, the polymerase is translated as a fusion with other non-structural proteins via readthrough of a UGA stop codon. Surprisingly, earlier work reported that the signal for efficient readthrough comprises a single cytidine residue 3′-adjacent to the UGA. However, analysis of variability at synonymous sites revealed strikingly enhanced conservation within the ∼150 nt 3′-adjacent to the UGA, and RNA folding algorithms revealed the potential for a phylogenetically conserved stem–loop structure in the same region. Mutational analysis of the predicted structure demonstrated that the stem–loop increases readthrough by up to 10-fold. The same computational analysis indicated that similar RNA structures are likely to be relevant to readthrough in certain plant virus genera, notably Furovirus, Pomovirus, Tobravirus, Pecluvirus and Benyvirus, as well as the Drosophilia gene kelch. These results suggest that 3′ RNA stimulatory structures feature in a much larger proportion of readthrough cases than previously anticipated, and provide a new criterion for assessing the large number of cellular readthrough candidates that are currently being revealed by comparative sequence analysis.",2011 Aug 27,"['Firth, Andrew E.', 'Wills, Norma M.', 'Gesteland, Raymond F.', 'Atkins, John F.']",Nucleic Acids Res,,,False
b525a9de80ca7225b057a792dc3e27f1b7a43436,PMC,"Bats, emerging infectious diseases, and the rabies paradigm revisited",http://dx.doi.org/10.3402/ehtj.v4i0.7159,PMC3168224,24149032,CC BY-NC,"The significance of bats as sources of emerging infectious diseases has been increasingly appreciated, and new data have been accumulated rapidly during recent years. For some emerging pathogens the bat origin has been confirmed (such as lyssaviruses, henipaviruses, coronaviruses), for other it has been suggested (filoviruses). Several recently identified viruses remain to be ‘orphan’ but have a potential for further emergence (such as Tioman, Menangle, and Pulau viruses). In the present review we summarize information on major bat-associated emerging infections and discuss specific characteristics of bats as carriers of pathogens (from evolutionary, ecological, and immunological positions). We also discuss drivers and forces of an infectious disease emergence and describe various existing and potential approaches for control and prevention of such infections at individual, populational, and societal levels.",2011 Jun 20,"['Kuzmin, Ivan V.', 'Bozick, Brooke', 'Guagliardo, Sarah A.', 'Kunkel, Rebekah', 'Shak, Joshua R.', 'Tong, Suxiang', 'Rupprecht, Charles E']",Emerg Health Threats J,,,True
8198fbb4175a2f90bcb43dafc0a365677c916d77,PMC,Using a Pan-Viral Microarray Assay (Virochip) to Screen Clinical Samples for Viral Pathogens,http://dx.doi.org/10.3791/2536,PMC3169278,21559002,CC BY-NC-ND,"The diagnosis of viral causes of many infectious diseases is difficult due to the inherent sequence diversity of viruses as well as the ongoing emergence of novel viral pathogens, such as SARS coronavirus and 2009 pandemic H1N1 influenza virus, that are not detectable by traditional methods. To address these challenges, we have previously developed and validated a pan-viral microarray platform called the Virochip with the capacity to detect all known viruses as well as novel variants on the basis of conserved sequence homology(1). Using the Virochip, we have identified the full spectrum of viruses associated with respiratory infections, including cases of unexplained critical illness in hospitalized patients, with a sensitivity equivalent to or superior to conventional clinical testing(2-5). The Virochip has also been used to identify novel viruses, including the SARS coronavirus(6,7), a novel rhinovirus clade(5), XMRV (a retrovirus linked to prostate cancer)(8), avian bornavirus (the cause of a wasting disease in parrots)(9), and a novel cardiovirus in children with respiratory and diarrheal illness(10). The current version of the Virochip has been ported to an Agilent microarray platform and consists of ~36,000 probes derived from over ~1,500 viruses in GenBank as of December of 2009. Here we demonstrate the steps involved in processing a Virochip assay from start to finish (~24 hour turnaround time), including sample nucleic acid extraction, PCR amplification using random primers, fluorescent dye incorporation, and microarray hybridization, scanning, and analysis.",2011 Apr 27,"['Chen, Eunice C.', 'Miller, Steve A.', 'DeRisi, Joseph L.', 'Chiu, Charles Y.']",J Vis Exp,,,True
ed9bd29d43d2781618f8c3133dd85492af8960ce,PMC,UK newspapers' representations of the 2009–10 outbreak of swine flu: one health scare not over-hyped by the media?,http://dx.doi.org/10.1136/jech.2010.119875,PMC3171979,21131303,CC BY-NC,"BACKGROUND: A/H1N1, more commonly referred to as swine flu, emerged in Mexico in spring 2009. It rapidly spread across the world and was classed as a global pandemic on 11 June 2009. OBJECTIVE: To analyse UK newsprint coverage of the swine flu pandemic. METHODS: Content analysis of 2374 newsprint articles published in eight UK national newspapers between 1 March 2009 and 28 February 2010. RESULTS: Newsprint coverage of the swine flu epidemic was immense. The threat from swine flu was portrayed as greatest in the spring and summer of 2009 when scientific uncertainties about the impact on the UK and global population were at their height and when swine flu cases in the UK first peaked. Thereafter the number of news articles waned, failing to mirror the October peak in flu cases as the virus failed to be as virulent as first feared. Content analysis found little evidence of the media ‘over-hyping’ the swine flu pandemic. CONCLUSIONS: The news media's role as a disseminator of scientific information is particularly important in areas of risk perception. Despite a succession of health scares in recent years in which the media has been accused of exaggerating the risks and contributing to public misunderstandings of the issues, this analysis suggests that the UK newsprint reporting of swine flu in the 2009–10 outbreak was largely measured. The news media's role as disseminators of factual health information on swine flu is to be welcomed, particularly in relation to their handling and responsible reporting on scientific uncertainty.",2011 Oct 3,"['Hilton, Shona', 'Hunt, Kate']",J Epidemiol Community Health,,,True
15d061338f90460e59acb68d6cd52f5e776e53c1,PMC,Acute disseminated encephalomyelitis in children: differential diagnosis from multiple sclerosis on the basis of clinical course,http://dx.doi.org/10.3345/kjp.2011.54.6.234,PMC3174358,21949517,CC BY-NC,"Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease of the central nervous system (CNS) that typically presents as a monophasic disorder associated with multifocal neurologic symptoms and encephalopathy. ADEM is considered an autoimmune disorder that is triggered by an environmental stimulus in genetically susceptible individuals. The diagnosis of ADEM is based on clinical and radiological features. Most children with ADEM initially present with fever, meningeal signs, and acute encephalopathy. The level of consciousness ranges from lethargy to frank coma. Deep and subcortical white-matter lesions and gray-matter lesions such as thalami and basal ganglia on magnetic resonance imaging (MRI) are associated with ADEM. In a child who presents with signs of encephalitis, bacterial and viral meningitis or encephalitis must be ruled out. Sequential MRI is required to confirm the diagnosis of ADEM, as relapses with the appearance of new lesions on MRI may suggest either multiphasic ADEM or multiple sclerosis (MS). Pediatric MS, defined as onset of MS before the age of 16, is being increasingly recognized. MS is characterized by recurrent episodes of demyelination in the CNS separated in space and time. The McDonald criteria for diagnosis of MS include evidence from MRI and allow the clinician to make a diagnosis of clinically definite MS on the basis of the interval preceding the development of new white matter lesions, even in the absence of new clinical findings. The most important alternative diagnosis to MS is ADEM. At the initial presentation, the 2 disorders cannot be distinguished with certainty. Therefore, prolonged follow-up is needed to establish a diagnosis.",2011 Jun 30,"Lee, Yun Jin",Korean J Pediatr,,,True
102e8dd2d010be4e7f39f8e2d0c84190ee87d9e2,PMC,Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4(+) T Cell Line,http://dx.doi.org/10.1128/mBio.00134-11,PMC3175625,21933919,CC BY-NC-SA,"Next-generation sequencing (NGS) enables the highly sensitive measurement of whole transcriptomes. We report the first application to our knowledge of this technology to the analysis of RNA from a CD4(+) T cell line infected with intact HIV. We sequenced the total mRNA from infected cells and detected differences in the expression of both host and viral mRNA. Viral reads represented a large portion of the total mapped sequencing reads: approximately 20% at 12 h postinfection (hpi) and 40% at 24 hpi. We also detected a small but significant suppression of T cell activation-related genes at 12 hpi. This suppression persisted and expanded by 24 hpi, providing new possible markers of virus-induced T cell cytopathology. By 24 hpi, the expression of over 50% of detectable host loci was also altered, indicating widespread alteration of host processes, including RNA processing, splicing, and transport to an extent not previously reported. In addition, next-generation sequencing provided insights into alternative viral RNA splice events and the expression of noncoding RNAs, including microRNA host genes.",2011 Sep 20,"['Chang, Stewart T.', 'Sova, Pavel', 'Peng, Xinxia', 'Weiss, Jeffrey', 'Law, G. Lynn', 'Palermo, Robert E.', 'Katze, Michael G.']",mBio,,,True
65beb50ed2b8aa31f03a36f1538aa6e6e8b94b89,PMC,Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4(+) T Cell Line,http://dx.doi.org/10.1128/mBio.00134-11,PMC3175625,21933919,CC BY-NC-SA,"Next-generation sequencing (NGS) enables the highly sensitive measurement of whole transcriptomes. We report the first application to our knowledge of this technology to the analysis of RNA from a CD4(+) T cell line infected with intact HIV. We sequenced the total mRNA from infected cells and detected differences in the expression of both host and viral mRNA. Viral reads represented a large portion of the total mapped sequencing reads: approximately 20% at 12 h postinfection (hpi) and 40% at 24 hpi. We also detected a small but significant suppression of T cell activation-related genes at 12 hpi. This suppression persisted and expanded by 24 hpi, providing new possible markers of virus-induced T cell cytopathology. By 24 hpi, the expression of over 50% of detectable host loci was also altered, indicating widespread alteration of host processes, including RNA processing, splicing, and transport to an extent not previously reported. In addition, next-generation sequencing provided insights into alternative viral RNA splice events and the expression of noncoding RNAs, including microRNA host genes.",2011 Sep 20,"['Chang, Stewart T.', 'Sova, Pavel', 'Peng, Xinxia', 'Weiss, Jeffrey', 'Law, G. Lynn', 'Palermo, Robert E.', 'Katze, Michael G.']",mBio,,,False
b7139d0f26c9774a842222de92d3e1e40c148699,PMC,Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4(+) T Cell Line,http://dx.doi.org/10.1128/mBio.00134-11,PMC3175625,21933919,CC BY-NC-SA,"Next-generation sequencing (NGS) enables the highly sensitive measurement of whole transcriptomes. We report the first application to our knowledge of this technology to the analysis of RNA from a CD4(+) T cell line infected with intact HIV. We sequenced the total mRNA from infected cells and detected differences in the expression of both host and viral mRNA. Viral reads represented a large portion of the total mapped sequencing reads: approximately 20% at 12 h postinfection (hpi) and 40% at 24 hpi. We also detected a small but significant suppression of T cell activation-related genes at 12 hpi. This suppression persisted and expanded by 24 hpi, providing new possible markers of virus-induced T cell cytopathology. By 24 hpi, the expression of over 50% of detectable host loci was also altered, indicating widespread alteration of host processes, including RNA processing, splicing, and transport to an extent not previously reported. In addition, next-generation sequencing provided insights into alternative viral RNA splice events and the expression of noncoding RNAs, including microRNA host genes.",2011 Sep 20,"['Chang, Stewart T.', 'Sova, Pavel', 'Peng, Xinxia', 'Weiss, Jeffrey', 'Law, G. Lynn', 'Palermo, Robert E.', 'Katze, Michael G.']",mBio,,,False
02228901fe368ffb73327591a58a4431c312fc25,PMC,Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4(+) T Cell Line,http://dx.doi.org/10.1128/mBio.00134-11,PMC3175625,21933919,CC BY-NC-SA,"Next-generation sequencing (NGS) enables the highly sensitive measurement of whole transcriptomes. We report the first application to our knowledge of this technology to the analysis of RNA from a CD4(+) T cell line infected with intact HIV. We sequenced the total mRNA from infected cells and detected differences in the expression of both host and viral mRNA. Viral reads represented a large portion of the total mapped sequencing reads: approximately 20% at 12 h postinfection (hpi) and 40% at 24 hpi. We also detected a small but significant suppression of T cell activation-related genes at 12 hpi. This suppression persisted and expanded by 24 hpi, providing new possible markers of virus-induced T cell cytopathology. By 24 hpi, the expression of over 50% of detectable host loci was also altered, indicating widespread alteration of host processes, including RNA processing, splicing, and transport to an extent not previously reported. In addition, next-generation sequencing provided insights into alternative viral RNA splice events and the expression of noncoding RNAs, including microRNA host genes.",2011 Sep 20,"['Chang, Stewart T.', 'Sova, Pavel', 'Peng, Xinxia', 'Weiss, Jeffrey', 'Law, G. Lynn', 'Palermo, Robert E.', 'Katze, Michael G.']",mBio,,,False
26c0767fd866d344dc410abe37641bf0a82704ee,PMC,Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4(+) T Cell Line,http://dx.doi.org/10.1128/mBio.00134-11,PMC3175625,21933919,CC BY-NC-SA,"Next-generation sequencing (NGS) enables the highly sensitive measurement of whole transcriptomes. We report the first application to our knowledge of this technology to the analysis of RNA from a CD4(+) T cell line infected with intact HIV. We sequenced the total mRNA from infected cells and detected differences in the expression of both host and viral mRNA. Viral reads represented a large portion of the total mapped sequencing reads: approximately 20% at 12 h postinfection (hpi) and 40% at 24 hpi. We also detected a small but significant suppression of T cell activation-related genes at 12 hpi. This suppression persisted and expanded by 24 hpi, providing new possible markers of virus-induced T cell cytopathology. By 24 hpi, the expression of over 50% of detectable host loci was also altered, indicating widespread alteration of host processes, including RNA processing, splicing, and transport to an extent not previously reported. In addition, next-generation sequencing provided insights into alternative viral RNA splice events and the expression of noncoding RNAs, including microRNA host genes.",2011 Sep 20,"['Chang, Stewart T.', 'Sova, Pavel', 'Peng, Xinxia', 'Weiss, Jeffrey', 'Law, G. Lynn', 'Palermo, Robert E.', 'Katze, Michael G.']",mBio,,,False
4b58ea6fa93cd395723124a6b29501c979bd169b,PMC,Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4(+) T Cell Line,http://dx.doi.org/10.1128/mBio.00134-11,PMC3175625,21933919,CC BY-NC-SA,"Next-generation sequencing (NGS) enables the highly sensitive measurement of whole transcriptomes. We report the first application to our knowledge of this technology to the analysis of RNA from a CD4(+) T cell line infected with intact HIV. We sequenced the total mRNA from infected cells and detected differences in the expression of both host and viral mRNA. Viral reads represented a large portion of the total mapped sequencing reads: approximately 20% at 12 h postinfection (hpi) and 40% at 24 hpi. We also detected a small but significant suppression of T cell activation-related genes at 12 hpi. This suppression persisted and expanded by 24 hpi, providing new possible markers of virus-induced T cell cytopathology. By 24 hpi, the expression of over 50% of detectable host loci was also altered, indicating widespread alteration of host processes, including RNA processing, splicing, and transport to an extent not previously reported. In addition, next-generation sequencing provided insights into alternative viral RNA splice events and the expression of noncoding RNAs, including microRNA host genes.",2011 Sep 20,"['Chang, Stewart T.', 'Sova, Pavel', 'Peng, Xinxia', 'Weiss, Jeffrey', 'Law, G. Lynn', 'Palermo, Robert E.', 'Katze, Michael G.']",mBio,,,False
6b8378bdbe44c661ef37ad44d446720395211769,PMC,Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4(+) T Cell Line,http://dx.doi.org/10.1128/mBio.00134-11,PMC3175625,21933919,CC BY-NC-SA,"Next-generation sequencing (NGS) enables the highly sensitive measurement of whole transcriptomes. We report the first application to our knowledge of this technology to the analysis of RNA from a CD4(+) T cell line infected with intact HIV. We sequenced the total mRNA from infected cells and detected differences in the expression of both host and viral mRNA. Viral reads represented a large portion of the total mapped sequencing reads: approximately 20% at 12 h postinfection (hpi) and 40% at 24 hpi. We also detected a small but significant suppression of T cell activation-related genes at 12 hpi. This suppression persisted and expanded by 24 hpi, providing new possible markers of virus-induced T cell cytopathology. By 24 hpi, the expression of over 50% of detectable host loci was also altered, indicating widespread alteration of host processes, including RNA processing, splicing, and transport to an extent not previously reported. In addition, next-generation sequencing provided insights into alternative viral RNA splice events and the expression of noncoding RNAs, including microRNA host genes.",2011 Sep 20,"['Chang, Stewart T.', 'Sova, Pavel', 'Peng, Xinxia', 'Weiss, Jeffrey', 'Law, G. Lynn', 'Palermo, Robert E.', 'Katze, Michael G.']",mBio,,,False
aedc6d330de8d91479928ae8186ee5aba2fc03fe,PMC,Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4(+) T Cell Line,http://dx.doi.org/10.1128/mBio.00134-11,PMC3175625,21933919,CC BY-NC-SA,"Next-generation sequencing (NGS) enables the highly sensitive measurement of whole transcriptomes. We report the first application to our knowledge of this technology to the analysis of RNA from a CD4(+) T cell line infected with intact HIV. We sequenced the total mRNA from infected cells and detected differences in the expression of both host and viral mRNA. Viral reads represented a large portion of the total mapped sequencing reads: approximately 20% at 12 h postinfection (hpi) and 40% at 24 hpi. We also detected a small but significant suppression of T cell activation-related genes at 12 hpi. This suppression persisted and expanded by 24 hpi, providing new possible markers of virus-induced T cell cytopathology. By 24 hpi, the expression of over 50% of detectable host loci was also altered, indicating widespread alteration of host processes, including RNA processing, splicing, and transport to an extent not previously reported. In addition, next-generation sequencing provided insights into alternative viral RNA splice events and the expression of noncoding RNAs, including microRNA host genes.",2011 Sep 20,"['Chang, Stewart T.', 'Sova, Pavel', 'Peng, Xinxia', 'Weiss, Jeffrey', 'Law, G. Lynn', 'Palermo, Robert E.', 'Katze, Michael G.']",mBio,,,False
12eaefbf4f12a5b0945360795a9741fc89321a10,PMC,Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4(+) T Cell Line,http://dx.doi.org/10.1128/mBio.00134-11,PMC3175625,21933919,CC BY-NC-SA,"Next-generation sequencing (NGS) enables the highly sensitive measurement of whole transcriptomes. We report the first application to our knowledge of this technology to the analysis of RNA from a CD4(+) T cell line infected with intact HIV. We sequenced the total mRNA from infected cells and detected differences in the expression of both host and viral mRNA. Viral reads represented a large portion of the total mapped sequencing reads: approximately 20% at 12 h postinfection (hpi) and 40% at 24 hpi. We also detected a small but significant suppression of T cell activation-related genes at 12 hpi. This suppression persisted and expanded by 24 hpi, providing new possible markers of virus-induced T cell cytopathology. By 24 hpi, the expression of over 50% of detectable host loci was also altered, indicating widespread alteration of host processes, including RNA processing, splicing, and transport to an extent not previously reported. In addition, next-generation sequencing provided insights into alternative viral RNA splice events and the expression of noncoding RNAs, including microRNA host genes.",2011 Sep 20,"['Chang, Stewart T.', 'Sova, Pavel', 'Peng, Xinxia', 'Weiss, Jeffrey', 'Law, G. Lynn', 'Palermo, Robert E.', 'Katze, Michael G.']",mBio,,,False
4d796b07dbc513c769c5ec8bbf7baedda9791881,PMC,Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4(+) T Cell Line,http://dx.doi.org/10.1128/mBio.00134-11,PMC3175625,21933919,CC BY-NC-SA,"Next-generation sequencing (NGS) enables the highly sensitive measurement of whole transcriptomes. We report the first application to our knowledge of this technology to the analysis of RNA from a CD4(+) T cell line infected with intact HIV. We sequenced the total mRNA from infected cells and detected differences in the expression of both host and viral mRNA. Viral reads represented a large portion of the total mapped sequencing reads: approximately 20% at 12 h postinfection (hpi) and 40% at 24 hpi. We also detected a small but significant suppression of T cell activation-related genes at 12 hpi. This suppression persisted and expanded by 24 hpi, providing new possible markers of virus-induced T cell cytopathology. By 24 hpi, the expression of over 50% of detectable host loci was also altered, indicating widespread alteration of host processes, including RNA processing, splicing, and transport to an extent not previously reported. In addition, next-generation sequencing provided insights into alternative viral RNA splice events and the expression of noncoding RNAs, including microRNA host genes.",2011 Sep 20,"['Chang, Stewart T.', 'Sova, Pavel', 'Peng, Xinxia', 'Weiss, Jeffrey', 'Law, G. Lynn', 'Palermo, Robert E.', 'Katze, Michael G.']",mBio,,,False
a2a8f2e052717a80325eeb6f1ec3cfcb28a55151,PMC,Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4(+) T Cell Line,http://dx.doi.org/10.1128/mBio.00134-11,PMC3175625,21933919,CC BY-NC-SA,"Next-generation sequencing (NGS) enables the highly sensitive measurement of whole transcriptomes. We report the first application to our knowledge of this technology to the analysis of RNA from a CD4(+) T cell line infected with intact HIV. We sequenced the total mRNA from infected cells and detected differences in the expression of both host and viral mRNA. Viral reads represented a large portion of the total mapped sequencing reads: approximately 20% at 12 h postinfection (hpi) and 40% at 24 hpi. We also detected a small but significant suppression of T cell activation-related genes at 12 hpi. This suppression persisted and expanded by 24 hpi, providing new possible markers of virus-induced T cell cytopathology. By 24 hpi, the expression of over 50% of detectable host loci was also altered, indicating widespread alteration of host processes, including RNA processing, splicing, and transport to an extent not previously reported. In addition, next-generation sequencing provided insights into alternative viral RNA splice events and the expression of noncoding RNAs, including microRNA host genes.",2011 Sep 20,"['Chang, Stewart T.', 'Sova, Pavel', 'Peng, Xinxia', 'Weiss, Jeffrey', 'Law, G. Lynn', 'Palermo, Robert E.', 'Katze, Michael G.']",mBio,,,False
73aa8683fd7c4fd68b73f231b6bc3e609d4e9af9,PMC,Diauxic shift-dependent relocalization of decapping activators Dhh1 and Pat1 to polysomal complexes,http://dx.doi.org/10.1093/nar/gkr474,PMC3177209,21712243,CC BY-NC,"Dhh1 and Pat1 in yeast are mRNA decapping activators/translational repressors thought to play key roles in the transition of mRNAs from translation to degradation. However, little is known about the physical and functional relationships between these proteins and the translation machinery. We describe a previously unknown type of diauxic shift-dependent modulation of the intracellular locations of Dhh1 and Pat1. Like the formation of P bodies, this phenomenon changes the spatial relationship between components involved in translation and mRNA degradation. We report significant spatial separation of Dhh1 and Pat1 from ribosomes in exponentially growing cells. Moreover, biochemical analyses reveal that these proteins are excluded from polysomal complexes in exponentially growing cells, indicating that they may not be associated with active states of the translation machinery. In contrast, under diauxic growth shift conditions, Dhh1 and Pat1 are found to co-localize with polysomal complexes. This work suggests that Dhh1 and Pat1 functions are modulated by a re-localization mechanism that involves eIF4A. Pull-down experiments reveal that the intracellular binding partners of Dhh1 and Pat1 change as cells undergo the diauxic growth shift. This reveals a new dimension to the relationship between translation activity and interactions between mRNA, the translation machinery and decapping activator proteins.",2011 Sep 28,"['Drummond, Sheona P.', 'Hildyard, John', 'Firczuk, Helena', 'Reamtong, Onrapak', 'Li, Ning', 'Kannambath, Shichina', 'Claydon, Amy J.', 'Beynon, Robert J.', 'Eyers, Claire E.', 'McCarthy, John E. G.']",Nucleic Acids Res,,,True
84b0022b335dd937f19e6626dc0eb0fad9d499d5,PMC,Diauxic shift-dependent relocalization of decapping activators Dhh1 and Pat1 to polysomal complexes,http://dx.doi.org/10.1093/nar/gkr474,PMC3177209,21712243,CC BY-NC,"Dhh1 and Pat1 in yeast are mRNA decapping activators/translational repressors thought to play key roles in the transition of mRNAs from translation to degradation. However, little is known about the physical and functional relationships between these proteins and the translation machinery. We describe a previously unknown type of diauxic shift-dependent modulation of the intracellular locations of Dhh1 and Pat1. Like the formation of P bodies, this phenomenon changes the spatial relationship between components involved in translation and mRNA degradation. We report significant spatial separation of Dhh1 and Pat1 from ribosomes in exponentially growing cells. Moreover, biochemical analyses reveal that these proteins are excluded from polysomal complexes in exponentially growing cells, indicating that they may not be associated with active states of the translation machinery. In contrast, under diauxic growth shift conditions, Dhh1 and Pat1 are found to co-localize with polysomal complexes. This work suggests that Dhh1 and Pat1 functions are modulated by a re-localization mechanism that involves eIF4A. Pull-down experiments reveal that the intracellular binding partners of Dhh1 and Pat1 change as cells undergo the diauxic growth shift. This reveals a new dimension to the relationship between translation activity and interactions between mRNA, the translation machinery and decapping activator proteins.",2011 Sep 28,"['Drummond, Sheona P.', 'Hildyard, John', 'Firczuk, Helena', 'Reamtong, Onrapak', 'Li, Ning', 'Kannambath, Shichina', 'Claydon, Amy J.', 'Beynon, Robert J.', 'Eyers, Claire E.', 'McCarthy, John E. G.']",Nucleic Acids Res,,,False
9316c8c673768c7310978f482fcaa1d3bd62d547,PMC,Human metapneumovirus and human coronavirus infection and pathogenicity in Saudi children hospitalized with acute respiratory illness,http://dx.doi.org/10.4103/0256-4947.84633,PMC3183689,21911992,CC BY-NC-SA,"BACKGROUND AND OBJECTIVES: Human metapneumovirus (hMPV) and the Netherlands human coronavirus (HCoV-NL63) have been isolated from children with respiratory tract infection. The prevalence of these viruses has not been reported from Saudi Arabia. We sought to determine whether hMPV and HCoV-NL63 are responsible for acute respiratory illness and also to determine clinical features and severity of illness in the hospitalized pediatric patient population. DESIGN AND SETTING: Prospective hospital-based study from July 2007 to November 2008. PATIENTS AND METHODS: Nasopharyngeal specimens from children less than 16 years old who were suffering from acute respiratory diseases were tested for hMPV and HCoV-NL63 by reverse transcriptase–polymerase chain reaction. Samples were collected from July 2007 to November 2008. RESULTS: Both viruses were found among Saudi children with upper and lower respiratory tract diseases during the autumn and winter of 2007 and 2008, contributing to 11.1% of all viral diagnoses, with individual incidences of 8.3% (hMPV) and 2.8% (HCoV-NL63) among 489 specimens. Initial symptoms included fever, cough, and nasal congestion. Lower respiratory tract disease occurs in immunocompromised individuals and those with underlying conditions. Clinical findings of respiratory failure and culture-negative shock were established in 7 children infected with hMPV and having hematologic malignancies, myelofibrosis, Gaucher disease, and congenital immunodeficiency; 2 of the 7 patients died with acute respiratory failure. All children infected with HCoV-NL63 had underlying conditions; 1 of the 4 patients developed respiratory failure. CONCLUSION: hMPV and HCoV-NL63 are important causes of acute respiratory illness among hospitalized Saudi children. hMPV infection in the lower respiratory tract is associated with morbidity and mortality in immunocompromised children. HCoV-NL63 may cause severe lower respiratory disease with underlying conditions.",2011 Sep-Oct,"['Al Hajjar, Sami', 'Al Thawadi, Sahar', 'Al Seraihi, Amal', 'Al Muhsen, Saleh', 'Imambaccus, Hala']",Ann Saudi Med,,,True
ea5d20e07d05c8b241f90e6429f3daaacc844ecd,PMC,The Transformation of Enterovirus Replication Structures: a Three-Dimensional Study of Single- and Double-Membrane Compartments,http://dx.doi.org/10.1128/mBio.00166-11,PMC3187575,21972238,CC BY-NC-SA,"All positive-strand RNA viruses induce membrane structures in their host cells which are thought to serve as suitable microenvironments for viral RNA synthesis. The structures induced by enteroviruses, which are members of the family Picornaviridae, have so far been described as either single- or double-membrane vesicles (DMVs). Aside from the number of delimiting membranes, their exact architecture has also remained elusive due to the limitations of conventional electron microscopy. In this study, we used electron tomography (ET) to solve the three-dimensional (3-D) ultrastructure of these compartments. At different time points postinfection, coxsackievirus B3-infected cells were high-pressure frozen and freeze-substituted for ET analysis. The tomograms showed that during the exponential phase of viral RNA synthesis, closed smooth single-membrane tubules constituted the predominant virus-induced membrane structure, with a minor proportion of DMVs that were either closed or connected to the cytosol in a vase-like configuration. As infection progressed, the DMV number steadily increased, while the tubular single-membrane structures gradually disappeared. Late in infection, complex multilamellar structures, previously unreported, became apparent in the cytoplasm. Serial tomography disclosed that their basic unit is a DMV, which is enwrapped by one or multiple cisternae. ET also revealed striking intermediate structures that strongly support the conversion of single-membrane tubules into double-membrane and multilamellar structures by a process of membrane apposition, enwrapping, and fusion. Collectively, our work unravels the sequential appearance of distinct enterovirus-induced replication structures, elucidates their detailed 3-D architecture, and provides the basis for a model for their transformation during the course of infection.",2011 Oct 4,"['Limpens, Ronald W. A. L.', 'van der Schaar, Hilde M.', 'Kumar, Darshan', 'Koster, Abraham J.', 'Snijder, Eric J.', 'van Kuppeveld, Frank J. M.', 'Bárcena, Montserrat']",mBio,,,True
7aaaac381f47fcb8d47d69b810efd23a0db7bf15,PMC,Improved quality control processing of peptide-centric LC-MS proteomics data,http://dx.doi.org/10.1093/bioinformatics/btr479,PMC3187650,21852304,CC BY-NC,"Motivation: In the analysis of differential peptide peak intensities (i.e. abundance measures), LC-MS analyses with poor quality peptide abundance data can bias downstream statistical analyses and hence the biological interpretation for an otherwise high-quality dataset. Although considerable effort has been placed on assuring the quality of the peptide identification with respect to spectral processing, to date quality assessment of the subsequent peptide abundance data matrix has been limited to a subjective visual inspection of run-by-run correlation or individual peptide components. Identifying statistical outliers is a critical step in the processing of proteomics data as many of the downstream statistical analyses [e.g. analysis of variance (ANOVA)] rely upon accurate estimates of sample variance, and their results are influenced by extreme values. Results: We describe a novel multivariate statistical strategy for the identification of LC-MS runs with extreme peptide abundance distributions. Comparison with current method (run-by-run correlation) demonstrates a significantly better rate of identification of outlier runs by the multivariate strategy. Simulation studies also suggest that this strategy significantly outperforms correlation alone in the identification of statistically extreme liquid chromatography-mass spectrometry (LC-MS) runs. Availability: https://www.biopilot.org/docs/Software/RMD.php Contact: bj@pnl.gov Supplementary information: Supplementary material is available at Bioinformatics online.",2011 Oct 15,"['Matzke, Melissa M.', 'Waters, Katrina M.', 'Metz, Thomas O.', 'Jacobs, Jon M.', 'Sims, Amy C.', 'Baric, Ralph S.', 'Pounds, Joel G.', 'Webb-Robertson, Bobbie-Jo M.']",Bioinformatics,,,True
1caf61e8e3d5b1731f4048395e11f06f25cef858,PMC,Improved quality control processing of peptide-centric LC-MS proteomics data,http://dx.doi.org/10.1093/bioinformatics/btr479,PMC3187650,21852304,CC BY-NC,"Motivation: In the analysis of differential peptide peak intensities (i.e. abundance measures), LC-MS analyses with poor quality peptide abundance data can bias downstream statistical analyses and hence the biological interpretation for an otherwise high-quality dataset. Although considerable effort has been placed on assuring the quality of the peptide identification with respect to spectral processing, to date quality assessment of the subsequent peptide abundance data matrix has been limited to a subjective visual inspection of run-by-run correlation or individual peptide components. Identifying statistical outliers is a critical step in the processing of proteomics data as many of the downstream statistical analyses [e.g. analysis of variance (ANOVA)] rely upon accurate estimates of sample variance, and their results are influenced by extreme values. Results: We describe a novel multivariate statistical strategy for the identification of LC-MS runs with extreme peptide abundance distributions. Comparison with current method (run-by-run correlation) demonstrates a significantly better rate of identification of outlier runs by the multivariate strategy. Simulation studies also suggest that this strategy significantly outperforms correlation alone in the identification of statistically extreme liquid chromatography-mass spectrometry (LC-MS) runs. Availability: https://www.biopilot.org/docs/Software/RMD.php Contact: bj@pnl.gov Supplementary information: Supplementary material is available at Bioinformatics online.",2011 Oct 15,"['Matzke, Melissa M.', 'Waters, Katrina M.', 'Metz, Thomas O.', 'Jacobs, Jon M.', 'Sims, Amy C.', 'Baric, Ralph S.', 'Pounds, Joel G.', 'Webb-Robertson, Bobbie-Jo M.']",Bioinformatics,,,False
905e2b35719215760ebed8f3e93fdf6ea8ec9bcf,PMC,Surgical Transplantation of Mouse Neural Stem Cells into the Spinal Cords of Mice Infected with Neurotropic Mouse Hepatitis Virus,http://dx.doi.org/10.3791/2834,PMC3196172,21775959,CC BY-NC-ND,"Mice infected with the neurotropic JHM strain of mouse hepatitis virus (MHV) develop pathological and clinical outcomes similar to patients with the demyelinating disease Multiple Sclerosis (MS). We have shown that transplantation of NSCs into the spinal cords of sick mice results in a significant improvement in both remyelination and in clinical outcome. Cell replacement therapies for the treatment of chronic neurologic diseases are now a reality and in vivo models are vital in understanding the interactions between the engrafted cells and host tissue microenvironment. This presentation provides an adapted method for transplanting cells into the spinal cord of JHMV-infected mice. In brief, we provide a procedure for i) preparation of NSCs prior to transplant, ii) pre-operative care of mice, iii) exposure of the spinal cord via laminectomy, iv) stereotactic injection of NSCs, and iv) post-operative care.",2011 Jul 10,"['Carbajal, Kevin S.', 'Weinger, Jason G.', 'Whitman, Lucia M.', 'Schaumburg, Chris S.', 'Lane, Thomas E.']",J Vis Exp,,,True
2ea88246c467b56b00c2a792dbf3120299a624c7,PMC,Re-establishment of olfactory and taste functions,,PMC3201003,22073054,CC BY-NC-ND,"The incidence of olfactory disorders is appoximately 1-2% and they can seriously impact on the quality of life. Quantitative disorders (hyposmia, anosmia) are distinguished from qualitative disorders (parosmia, phantosmia). Olfactory disorders are classified according to the etiology and therapy is planned according to the underlying pathophysiology. In ENT patients olfactory disorders caused by sinonasal diseases are the most common ones, followed by postviral disorders. Therapy consists of topical and systemic steroids, whereas systemic application seems to be of greater value. It is very difficult to predict the improvement of olfactory function using surgery, moreover, the long term - success in surgery is questionable. Isolated taste disorders are rare and in most often caused by underlying diseases or side effects of medications. A meticulous history is necessary and helps to choose effective treatment. In selected cases zinc might be useful.",2005 Sep 28,"Welge-Lüssen, Antje",GMS Curr Top Otorhinolaryngol Head Neck Surg,,,True
169eb7d3419808c29066e6e5ed091a8d54bc214a,PMC,Two RNA-binding sites in plant fibrillarin provide interactions with various RNA substrates,http://dx.doi.org/10.1093/nar/gkr594,PMC3203579,21785141,CC BY-NC,"Fibrillarin, one of the major proteins of the nucleolus, plays several essential roles in ribosome biogenesis including pre-rRNA processing and 2′-O-ribose methylation of rRNA and snRNAs. Recently, it has been shown that fibrillarin plays a role in virus infections and is associated with viral RNPs. Here, we demonstrate the ability of recombinant fibrillarin 2 from Arabidopsis thaliana (AtFib2) to interact with RNAs of different lengths and types including rRNA, snoRNA, snRNA, siRNA and viral RNAs in vitro. Our data also indicate that AtFib2 possesses two RNA-binding sites in the central (138–179 amino acids) and C-terminal (225–281 amino acids) parts of the protein, respectively. The conserved GCVYAVEF octamer does not bind RNA directly as suggested earlier, but may assist with the proper folding of the central RNA-binding site.",2011 Nov 23,"['Rakitina, D. V.', 'Taliansky, Michael', 'Brown, J. W. S.', 'Kalinina, N. O.']",Nucleic Acids Res,,,True
1f3b676368e5c9a1582ab624cbf0884c383fddd2,PMC,Stem–loop structures can effectively substitute for an RNA pseudoknot in −1 ribosomal frameshifting,http://dx.doi.org/10.1093/nar/gkr579,PMC3203594,21803791,CC BY-NC,"−1 Programmed ribosomal frameshifting (PRF) in synthesizing the gag-pro precursor polyprotein of Simian retrovirus type-1 (SRV-1) is stimulated by a classical H-type pseudoknot which forms an extended triple helix involving base–base and base–sugar interactions between loop and stem nucleotides. Recently, we showed that mutation of bases involved in triple helix formation affected frameshifting, again emphasizing the role of the triple helix in −1 PRF. Here, we investigated the efficiency of hairpins of similar base pair composition as the SRV-1 gag-pro pseudoknot. Although not capable of triple helix formation they proved worthy stimulators of frameshifting. Subsequent investigation of ∼30 different hairpin constructs revealed that next to thermodynamic stability, loop size and composition and stem irregularities can influence frameshifting. Interestingly, hairpins carrying the stable GAAA tetraloop were significantly less shifty than other hairpins, including those with a UUCG motif. The data are discussed in relation to natural shifty hairpins.",2011 Nov 29,"['Yu, Chien-Hung', 'Noteborn, Mathieu H.', 'Pleij, Cornelis W. A.', 'Olsthoorn, René C. L.']",Nucleic Acids Res,,,True
5d98d889c1739957886a3c27dc6552e695fee2f7,PMC,Rhinitis in children less than 6 years of age: current knowledge and challenges,http://dx.doi.org/10.5415/apallergy.2011.1.3.115,PMC3206246,22053307,CC BY-NC,"Rhinitis is a disease of the upper airway characterized by runny and/or blocked nose and/or sneezing. Though not viewed as a life threatening condition, it is also recognized to impose significant burden to the quality of life of sufferers and their caretakers and imposes an economic cost to society. Through a PubMed online search of the literature from 2006 to September 2011, this paper aims to review the published literature on rhinitis in young children below the age of 6 years. It is apparent from epidemiology studies that rhinitis in this age group is a relatively common problem. The condition has a heterogenous etiology with classification into allergic and non-allergic rhinitis. Respiratory viral infections may play a role in the pathogenesis of long standing rhinitis, but definitive studies are still lacking. Treatment guidelines for management are lacking for this age group, and is a significant unmet need. Although the consensus is that co-morbidities including otitis media with effusion, adenoidal hypertrophy and asthma, are important considerations of management of these children. Pharmacotherapy is limited for young children especially for those below the age of 2 years. This review underscores the lack of understanding of rhinitis in early childhood and therefore the need for further research in this area.",2011 Oct 11,"['Hardjojo, Antony', 'Shek, Lynette PC', 'van Bever, Hugo PS', 'Lee, Bee Wah']",Asia Pac Allergy,,,True
90cc93e5eac1e836f5cbce50fe92ded531045abf,PMC,A novel synthesis and detection method for cap-associated adenosine modifications in mouse mRNA,http://dx.doi.org/10.1038/srep00126,PMC3216607,22355643,CC BY-NC-SA,"A method is described for the detection of certain nucleotide modifications adjacent to the 5' 7-methyl guanosine cap of mRNAs from individual genes. The method quantitatively measures the relative abundance of 2'-O-methyl and N(6),2'-O-dimethyladenosine, two of the most common modifications. In order to identify and quantitatify the amounts of N(6),2'-O-dimethyladenosine, a novel method for the synthesis of modified adenosine phosphoramidites was developed. This method is a one step synthesis and the product can directly be used for the production of N(6),2'-O-dimethyladenosine containing RNA oligonucleotides. The nature of the cap-adjacent nucleotides were shown to be characteristic for mRNAs from individual genes transcribed in liver and testis.",2011 Oct 24,"['Kruse, Susanne', 'Zhong, Silin', 'Bodi, Zsuzsanna', 'Button, James', 'Alcocer, Marcos J. C.', 'Hayes, Christopher J.', 'Fray, Rupert']",Sci Rep,,,True
c07b523c9bf9af72f5b6ee8b586b13ef619bb3ca,PMC,"Pharmacological targets in the ubiquitin system offer new ways of treating           cancer, neurodegenerative disorders and infectious diseases",http://dx.doi.org/10.1017/S1462399411002031,PMC3219211,22088887,CC BY-NC-SA,"Recent advances in the development and discovery of pharmacological interventions within the ubiquitin–proteasome system (UPS) have uncovered an enormous potential for possible novel treatments of neurodegenerative disease, cancer, immunological disorder and microbial infection. Interference with proteasome activity, although initially considered unlikely to be exploitable clinically, has already proved to be very effective against haematological malignancies, and more specific derivatives that target subsets of proteasomes are emerging. Recent small-molecule screens have revealed inhibitors against ubiquitin-conjugating and -deconjugating enzymes, many of which have been evaluated for their potential use as therapeutics, either as single agents or in synergy with other drugs. Here, we discuss recent advances in the characterisation of novel UPS modulators (in particular, inhibitors of ubiquitin-conjugating and -deconjugating enzymes) and how they pave the way towards new therapeutic approaches for the treatment of proteotoxic disease, cancer and microbial infection.",2011 Nov,"['Edelmann, Mariola J.', 'Nicholson, Benjamin', 'Kessler, Benedikt M.']",Expert Rev Mol Med,,,True
2def385170922c5786ea00a64f0c139460d23e2c,PMC,Mucosal Delivery of ACNPV Baculovirus Driving Expression of the Gal-Lectin LC3 Fragment Confers Protection against Amoebic Liver Abscess in Hamster,,PMC3221370,22110386,CC BY-NC-ND,"Mucosal vaccination against amoebiasis using the Gal-lectin of E. histolytica has been proposed as one of the leading strategies for controlling this human disease. However, most mucosal adjuvants used are toxic and the identification of safe delivery systems is necessary. Here, we evaluate the potential of a recombinant Autographa californica baculovirus driving the expression of the LC3 fragment of the Gal-lectin to confer protection against amoebic liver abscess (ALA) in hamsters following oral or nasal immunization. Hamsters immunized by oral route showed complete absence (57.9%) or partial development (21%) of ALA, resulting in some protection in 78.9% of animals when compared with the wild type baculovirus and sham control groups. In contrast, nasal immunization conferred only 21% of protection efficacy. Levels of ALA protection showed lineal correlation with the development of an anti-amoebic cellular immune response evaluated in spleens, but not with the induction of seric IgG anti-amoeba antibodies. These results suggest that baculovirus driving the expression of E. histolytica vaccine candidate antigens is useful for inducing protective cellular and humoral immune responses following oral immunization, and therefore it could be used as a system for mucosal delivery of an anti-amoebic vaccine.",2011 Nov 1,"['Meneses-Ruiz, DM', 'Laclette, JP', 'Aguilar-Díaz, H', 'Hernández-Ruiz, J', 'Luz-Madrigal, A', 'Sampieri, A', 'Vaca, L', 'Carrero, JC']",Int J Biol Sci,,,True
602981d75e74595af0e2de9e046a9cc9e05a1c0e,PMC,Integrative Deep Sequencing of the Mouse Lung Transcriptome Reveals Differential Expression of Diverse Classes of Small RNAs in Response to Respiratory Virus Infection,http://dx.doi.org/10.1128/mBio.00198-11,PMC3221602,22086488,CC BY-NC-SA,"We previously reported widespread differential expression of long non-protein-coding RNAs (ncRNAs) in response to virus infection. Here, we expanded the study through small RNA transcriptome sequencing analysis of the host response to both severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza virus infections across four founder mouse strains of the Collaborative Cross, a recombinant inbred mouse resource for mapping complex traits. We observed differential expression of over 200 small RNAs of diverse classes during infection. A majority of identified microRNAs (miRNAs) showed divergent changes in expression across mouse strains with respect to SARS-CoV and influenza virus infections and responded differently to a highly pathogenic reconstructed 1918 virus compared to a minimally pathogenic seasonal influenza virus isolate. Novel insights into miRNA expression changes, including the association with pathogenic outcomes and large differences between in vivo and in vitro experimental systems, were further elucidated by a survey of selected miRNAs across diverse virus infections. The small RNAs identified also included many non-miRNA small RNAs, such as small nucleolar RNAs (snoRNAs), in addition to nonannotated small RNAs. An integrative sequencing analysis of both small RNAs and long transcripts from the same samples showed that the results revealing differential expression of miRNAs during infection were largely due to transcriptional regulation and that the predicted miRNA-mRNA network could modulate global host responses to virus infection in a combinatorial fashion. These findings represent the first integrated sequencing analysis of the response of host small RNAs to virus infection and show that small RNAs are an integrated component of complex networks involved in regulating the host response to infection.",2011 Nov 15,"['Peng, Xinxia', 'Gralinski, Lisa', 'Ferris, Martin T.', 'Frieman, Matthew B.', 'Thomas, Matthew J.', 'Proll, Sean', 'Korth, Marcus J.', 'Tisoncik, Jennifer R.', 'Heise, Mark', 'Luo, Shujun', 'Schroth, Gary P.', 'Tumpey, Terrence M.', 'Li, Chengjun', 'Kawaoka, Yoshihiro', 'Baric, Ralph S.', 'Katze, Michael G.']",mBio,,,True
0b87e72027196fa9e7d6506729c533ad94b2c855,PMC,Integrative Deep Sequencing of the Mouse Lung Transcriptome Reveals Differential Expression of Diverse Classes of Small RNAs in Response to Respiratory Virus Infection,http://dx.doi.org/10.1128/mBio.00198-11,PMC3221602,22086488,CC BY-NC-SA,"We previously reported widespread differential expression of long non-protein-coding RNAs (ncRNAs) in response to virus infection. Here, we expanded the study through small RNA transcriptome sequencing analysis of the host response to both severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza virus infections across four founder mouse strains of the Collaborative Cross, a recombinant inbred mouse resource for mapping complex traits. We observed differential expression of over 200 small RNAs of diverse classes during infection. A majority of identified microRNAs (miRNAs) showed divergent changes in expression across mouse strains with respect to SARS-CoV and influenza virus infections and responded differently to a highly pathogenic reconstructed 1918 virus compared to a minimally pathogenic seasonal influenza virus isolate. Novel insights into miRNA expression changes, including the association with pathogenic outcomes and large differences between in vivo and in vitro experimental systems, were further elucidated by a survey of selected miRNAs across diverse virus infections. The small RNAs identified also included many non-miRNA small RNAs, such as small nucleolar RNAs (snoRNAs), in addition to nonannotated small RNAs. An integrative sequencing analysis of both small RNAs and long transcripts from the same samples showed that the results revealing differential expression of miRNAs during infection were largely due to transcriptional regulation and that the predicted miRNA-mRNA network could modulate global host responses to virus infection in a combinatorial fashion. These findings represent the first integrated sequencing analysis of the response of host small RNAs to virus infection and show that small RNAs are an integrated component of complex networks involved in regulating the host response to infection.",2011 Nov 15,"['Peng, Xinxia', 'Gralinski, Lisa', 'Ferris, Martin T.', 'Frieman, Matthew B.', 'Thomas, Matthew J.', 'Proll, Sean', 'Korth, Marcus J.', 'Tisoncik, Jennifer R.', 'Heise, Mark', 'Luo, Shujun', 'Schroth, Gary P.', 'Tumpey, Terrence M.', 'Li, Chengjun', 'Kawaoka, Yoshihiro', 'Baric, Ralph S.', 'Katze, Michael G.']",mBio,,,False
fcee0315b58942b16aaba3d1e753c7a9bd563e70,PMC,Integrative Deep Sequencing of the Mouse Lung Transcriptome Reveals Differential Expression of Diverse Classes of Small RNAs in Response to Respiratory Virus Infection,http://dx.doi.org/10.1128/mBio.00198-11,PMC3221602,22086488,CC BY-NC-SA,"We previously reported widespread differential expression of long non-protein-coding RNAs (ncRNAs) in response to virus infection. Here, we expanded the study through small RNA transcriptome sequencing analysis of the host response to both severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza virus infections across four founder mouse strains of the Collaborative Cross, a recombinant inbred mouse resource for mapping complex traits. We observed differential expression of over 200 small RNAs of diverse classes during infection. A majority of identified microRNAs (miRNAs) showed divergent changes in expression across mouse strains with respect to SARS-CoV and influenza virus infections and responded differently to a highly pathogenic reconstructed 1918 virus compared to a minimally pathogenic seasonal influenza virus isolate. Novel insights into miRNA expression changes, including the association with pathogenic outcomes and large differences between in vivo and in vitro experimental systems, were further elucidated by a survey of selected miRNAs across diverse virus infections. The small RNAs identified also included many non-miRNA small RNAs, such as small nucleolar RNAs (snoRNAs), in addition to nonannotated small RNAs. An integrative sequencing analysis of both small RNAs and long transcripts from the same samples showed that the results revealing differential expression of miRNAs during infection were largely due to transcriptional regulation and that the predicted miRNA-mRNA network could modulate global host responses to virus infection in a combinatorial fashion. These findings represent the first integrated sequencing analysis of the response of host small RNAs to virus infection and show that small RNAs are an integrated component of complex networks involved in regulating the host response to infection.",2011 Nov 15,"['Peng, Xinxia', 'Gralinski, Lisa', 'Ferris, Martin T.', 'Frieman, Matthew B.', 'Thomas, Matthew J.', 'Proll, Sean', 'Korth, Marcus J.', 'Tisoncik, Jennifer R.', 'Heise, Mark', 'Luo, Shujun', 'Schroth, Gary P.', 'Tumpey, Terrence M.', 'Li, Chengjun', 'Kawaoka, Yoshihiro', 'Baric, Ralph S.', 'Katze, Michael G.']",mBio,,,False
cba7d4b8d0dfb228d8648717c5f64d51f3e11473,PMC,Integrative Deep Sequencing of the Mouse Lung Transcriptome Reveals Differential Expression of Diverse Classes of Small RNAs in Response to Respiratory Virus Infection,http://dx.doi.org/10.1128/mBio.00198-11,PMC3221602,22086488,CC BY-NC-SA,"We previously reported widespread differential expression of long non-protein-coding RNAs (ncRNAs) in response to virus infection. Here, we expanded the study through small RNA transcriptome sequencing analysis of the host response to both severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza virus infections across four founder mouse strains of the Collaborative Cross, a recombinant inbred mouse resource for mapping complex traits. We observed differential expression of over 200 small RNAs of diverse classes during infection. A majority of identified microRNAs (miRNAs) showed divergent changes in expression across mouse strains with respect to SARS-CoV and influenza virus infections and responded differently to a highly pathogenic reconstructed 1918 virus compared to a minimally pathogenic seasonal influenza virus isolate. Novel insights into miRNA expression changes, including the association with pathogenic outcomes and large differences between in vivo and in vitro experimental systems, were further elucidated by a survey of selected miRNAs across diverse virus infections. The small RNAs identified also included many non-miRNA small RNAs, such as small nucleolar RNAs (snoRNAs), in addition to nonannotated small RNAs. An integrative sequencing analysis of both small RNAs and long transcripts from the same samples showed that the results revealing differential expression of miRNAs during infection were largely due to transcriptional regulation and that the predicted miRNA-mRNA network could modulate global host responses to virus infection in a combinatorial fashion. These findings represent the first integrated sequencing analysis of the response of host small RNAs to virus infection and show that small RNAs are an integrated component of complex networks involved in regulating the host response to infection.",2011 Nov 15,"['Peng, Xinxia', 'Gralinski, Lisa', 'Ferris, Martin T.', 'Frieman, Matthew B.', 'Thomas, Matthew J.', 'Proll, Sean', 'Korth, Marcus J.', 'Tisoncik, Jennifer R.', 'Heise, Mark', 'Luo, Shujun', 'Schroth, Gary P.', 'Tumpey, Terrence M.', 'Li, Chengjun', 'Kawaoka, Yoshihiro', 'Baric, Ralph S.', 'Katze, Michael G.']",mBio,,,False
5e6e328bad7fac0c03bd784b54dfd6052151f2d2,PMC,Integrative Deep Sequencing of the Mouse Lung Transcriptome Reveals Differential Expression of Diverse Classes of Small RNAs in Response to Respiratory Virus Infection,http://dx.doi.org/10.1128/mBio.00198-11,PMC3221602,22086488,CC BY-NC-SA,"We previously reported widespread differential expression of long non-protein-coding RNAs (ncRNAs) in response to virus infection. Here, we expanded the study through small RNA transcriptome sequencing analysis of the host response to both severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza virus infections across four founder mouse strains of the Collaborative Cross, a recombinant inbred mouse resource for mapping complex traits. We observed differential expression of over 200 small RNAs of diverse classes during infection. A majority of identified microRNAs (miRNAs) showed divergent changes in expression across mouse strains with respect to SARS-CoV and influenza virus infections and responded differently to a highly pathogenic reconstructed 1918 virus compared to a minimally pathogenic seasonal influenza virus isolate. Novel insights into miRNA expression changes, including the association with pathogenic outcomes and large differences between in vivo and in vitro experimental systems, were further elucidated by a survey of selected miRNAs across diverse virus infections. The small RNAs identified also included many non-miRNA small RNAs, such as small nucleolar RNAs (snoRNAs), in addition to nonannotated small RNAs. An integrative sequencing analysis of both small RNAs and long transcripts from the same samples showed that the results revealing differential expression of miRNAs during infection were largely due to transcriptional regulation and that the predicted miRNA-mRNA network could modulate global host responses to virus infection in a combinatorial fashion. These findings represent the first integrated sequencing analysis of the response of host small RNAs to virus infection and show that small RNAs are an integrated component of complex networks involved in regulating the host response to infection.",2011 Nov 15,"['Peng, Xinxia', 'Gralinski, Lisa', 'Ferris, Martin T.', 'Frieman, Matthew B.', 'Thomas, Matthew J.', 'Proll, Sean', 'Korth, Marcus J.', 'Tisoncik, Jennifer R.', 'Heise, Mark', 'Luo, Shujun', 'Schroth, Gary P.', 'Tumpey, Terrence M.', 'Li, Chengjun', 'Kawaoka, Yoshihiro', 'Baric, Ralph S.', 'Katze, Michael G.']",mBio,,,False
c9594f4c497dee46ab191d51597153031d157ad1,PMC,Integrative Deep Sequencing of the Mouse Lung Transcriptome Reveals Differential Expression of Diverse Classes of Small RNAs in Response to Respiratory Virus Infection,http://dx.doi.org/10.1128/mBio.00198-11,PMC3221602,22086488,CC BY-NC-SA,"We previously reported widespread differential expression of long non-protein-coding RNAs (ncRNAs) in response to virus infection. Here, we expanded the study through small RNA transcriptome sequencing analysis of the host response to both severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza virus infections across four founder mouse strains of the Collaborative Cross, a recombinant inbred mouse resource for mapping complex traits. We observed differential expression of over 200 small RNAs of diverse classes during infection. A majority of identified microRNAs (miRNAs) showed divergent changes in expression across mouse strains with respect to SARS-CoV and influenza virus infections and responded differently to a highly pathogenic reconstructed 1918 virus compared to a minimally pathogenic seasonal influenza virus isolate. Novel insights into miRNA expression changes, including the association with pathogenic outcomes and large differences between in vivo and in vitro experimental systems, were further elucidated by a survey of selected miRNAs across diverse virus infections. The small RNAs identified also included many non-miRNA small RNAs, such as small nucleolar RNAs (snoRNAs), in addition to nonannotated small RNAs. An integrative sequencing analysis of both small RNAs and long transcripts from the same samples showed that the results revealing differential expression of miRNAs during infection were largely due to transcriptional regulation and that the predicted miRNA-mRNA network could modulate global host responses to virus infection in a combinatorial fashion. These findings represent the first integrated sequencing analysis of the response of host small RNAs to virus infection and show that small RNAs are an integrated component of complex networks involved in regulating the host response to infection.",2011 Nov 15,"['Peng, Xinxia', 'Gralinski, Lisa', 'Ferris, Martin T.', 'Frieman, Matthew B.', 'Thomas, Matthew J.', 'Proll, Sean', 'Korth, Marcus J.', 'Tisoncik, Jennifer R.', 'Heise, Mark', 'Luo, Shujun', 'Schroth, Gary P.', 'Tumpey, Terrence M.', 'Li, Chengjun', 'Kawaoka, Yoshihiro', 'Baric, Ralph S.', 'Katze, Michael G.']",mBio,,,False
d15b3385ed7c3b73c8ed34ca45664e1a495be94d,PMC,Integrative Deep Sequencing of the Mouse Lung Transcriptome Reveals Differential Expression of Diverse Classes of Small RNAs in Response to Respiratory Virus Infection,http://dx.doi.org/10.1128/mBio.00198-11,PMC3221602,22086488,CC BY-NC-SA,"We previously reported widespread differential expression of long non-protein-coding RNAs (ncRNAs) in response to virus infection. Here, we expanded the study through small RNA transcriptome sequencing analysis of the host response to both severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza virus infections across four founder mouse strains of the Collaborative Cross, a recombinant inbred mouse resource for mapping complex traits. We observed differential expression of over 200 small RNAs of diverse classes during infection. A majority of identified microRNAs (miRNAs) showed divergent changes in expression across mouse strains with respect to SARS-CoV and influenza virus infections and responded differently to a highly pathogenic reconstructed 1918 virus compared to a minimally pathogenic seasonal influenza virus isolate. Novel insights into miRNA expression changes, including the association with pathogenic outcomes and large differences between in vivo and in vitro experimental systems, were further elucidated by a survey of selected miRNAs across diverse virus infections. The small RNAs identified also included many non-miRNA small RNAs, such as small nucleolar RNAs (snoRNAs), in addition to nonannotated small RNAs. An integrative sequencing analysis of both small RNAs and long transcripts from the same samples showed that the results revealing differential expression of miRNAs during infection were largely due to transcriptional regulation and that the predicted miRNA-mRNA network could modulate global host responses to virus infection in a combinatorial fashion. These findings represent the first integrated sequencing analysis of the response of host small RNAs to virus infection and show that small RNAs are an integrated component of complex networks involved in regulating the host response to infection.",2011 Nov 15,"['Peng, Xinxia', 'Gralinski, Lisa', 'Ferris, Martin T.', 'Frieman, Matthew B.', 'Thomas, Matthew J.', 'Proll, Sean', 'Korth, Marcus J.', 'Tisoncik, Jennifer R.', 'Heise, Mark', 'Luo, Shujun', 'Schroth, Gary P.', 'Tumpey, Terrence M.', 'Li, Chengjun', 'Kawaoka, Yoshihiro', 'Baric, Ralph S.', 'Katze, Michael G.']",mBio,,,False
5738e88fe3a742f9f6f69919bd4e6b094d52eded,PMC,Clinical instructors' perception of a faculty development programme promoting postgraduate year-1 (PGY(1)) residents' ACGME six core competencies: a 2-year study,http://dx.doi.org/10.1136/bmjopen-2011-000200,PMC3225591,22116089,CC BY-NC,"OBJECTIVE: The six core competencies designated by Accreditation Council for Graduate Medical Education (ACGME) are essential for establishing a patient centre holistic medical system. The authors developed a faculty programme to promote the postgraduate year 1 (PGY(1)) resident, ACGME six core competencies. The study aims to assess the clinical instructors' perception, attitudes and subjective impression towards the various sessions of the ‘faculty development programme for teaching ACGME competencies.’ METHODS: During 2009 and 2010, 134 clinical instructors participated in the programme to establish their ability to teach and assess PGY(1) residents about ACGME competencies. RESULTS: The participants in the faculty development programme reported that the skills most often used while teaching were learnt during circuit and itinerant bedside, physical examination teaching, mini-clinical evaluation exercise (mini-CEX) evaluation demonstration, training workshop and videotapes of ‘how to teach ACGME competencies.’ Participants reported that circuit bedside teaching and mini-CEX evaluation demonstrations helped them in the interpersonal and communication skills domain, and that the itinerant teaching demonstrations helped them in the professionalism domain, while physical examination teaching and mini-CEX evaluation demonstrations helped them in the patients' care domain. Both the training workshop and videotape session increase familiarity with teaching and assessing skills. Participants who applied the skills learnt from the faculty development programme the most in their teaching and assessment came from internal medicine departments, were young attending physician and had experience as PGY(1) clinical instructors. CONCLUSIONS: According to the clinical instructors' response, our faculty development programme effectively increased their familiarity with various teaching and assessment skills needed to teach PGY(1) residents and ACGME competencies, and these clinical instructors also then subsequently apply these skills.",2011 Nov 24,"['Lee, Fa-Yauh', 'Yang, Ying-Ying', 'Hsu, Hui-Chi', 'Chuang, Chiao-Lin', 'Lee, Wei-Shin', 'Chang, Ching-Chih', 'Huang, Chia-Chang', 'Chen, Jaw-Wen', 'Cheng, Hao-Min', 'Jap, Tjin-Shing']",BMJ Open,,,True
1919f9569a8e073accc1c8a105ec36a56ddf569c,PMC,Clinical instructors' perception of a faculty development programme promoting postgraduate year-1 (PGY(1)) residents' ACGME six core competencies: a 2-year study,http://dx.doi.org/10.1136/bmjopen-2011-000200,PMC3225591,22116089,CC BY-NC,"OBJECTIVE: The six core competencies designated by Accreditation Council for Graduate Medical Education (ACGME) are essential for establishing a patient centre holistic medical system. The authors developed a faculty programme to promote the postgraduate year 1 (PGY(1)) resident, ACGME six core competencies. The study aims to assess the clinical instructors' perception, attitudes and subjective impression towards the various sessions of the ‘faculty development programme for teaching ACGME competencies.’ METHODS: During 2009 and 2010, 134 clinical instructors participated in the programme to establish their ability to teach and assess PGY(1) residents about ACGME competencies. RESULTS: The participants in the faculty development programme reported that the skills most often used while teaching were learnt during circuit and itinerant bedside, physical examination teaching, mini-clinical evaluation exercise (mini-CEX) evaluation demonstration, training workshop and videotapes of ‘how to teach ACGME competencies.’ Participants reported that circuit bedside teaching and mini-CEX evaluation demonstrations helped them in the interpersonal and communication skills domain, and that the itinerant teaching demonstrations helped them in the professionalism domain, while physical examination teaching and mini-CEX evaluation demonstrations helped them in the patients' care domain. Both the training workshop and videotape session increase familiarity with teaching and assessing skills. Participants who applied the skills learnt from the faculty development programme the most in their teaching and assessment came from internal medicine departments, were young attending physician and had experience as PGY(1) clinical instructors. CONCLUSIONS: According to the clinical instructors' response, our faculty development programme effectively increased their familiarity with various teaching and assessment skills needed to teach PGY(1) residents and ACGME competencies, and these clinical instructors also then subsequently apply these skills.",2011 Nov 24,"['Lee, Fa-Yauh', 'Yang, Ying-Ying', 'Hsu, Hui-Chi', 'Chuang, Chiao-Lin', 'Lee, Wei-Shin', 'Chang, Ching-Chih', 'Huang, Chia-Chang', 'Chen, Jaw-Wen', 'Cheng, Hao-Min', 'Jap, Tjin-Shing']",BMJ Open,,,True
94328f43caa23f1a8692c582a7a050242f945db7,PMC,Clinical instructors' perception of a faculty development programme promoting postgraduate year-1 (PGY(1)) residents' ACGME six core competencies: a 2-year study,http://dx.doi.org/10.1136/bmjopen-2011-000200,PMC3225591,22116089,CC BY-NC,"OBJECTIVE: The six core competencies designated by Accreditation Council for Graduate Medical Education (ACGME) are essential for establishing a patient centre holistic medical system. The authors developed a faculty programme to promote the postgraduate year 1 (PGY(1)) resident, ACGME six core competencies. The study aims to assess the clinical instructors' perception, attitudes and subjective impression towards the various sessions of the ‘faculty development programme for teaching ACGME competencies.’ METHODS: During 2009 and 2010, 134 clinical instructors participated in the programme to establish their ability to teach and assess PGY(1) residents about ACGME competencies. RESULTS: The participants in the faculty development programme reported that the skills most often used while teaching were learnt during circuit and itinerant bedside, physical examination teaching, mini-clinical evaluation exercise (mini-CEX) evaluation demonstration, training workshop and videotapes of ‘how to teach ACGME competencies.’ Participants reported that circuit bedside teaching and mini-CEX evaluation demonstrations helped them in the interpersonal and communication skills domain, and that the itinerant teaching demonstrations helped them in the professionalism domain, while physical examination teaching and mini-CEX evaluation demonstrations helped them in the patients' care domain. Both the training workshop and videotape session increase familiarity with teaching and assessing skills. Participants who applied the skills learnt from the faculty development programme the most in their teaching and assessment came from internal medicine departments, were young attending physician and had experience as PGY(1) clinical instructors. CONCLUSIONS: According to the clinical instructors' response, our faculty development programme effectively increased their familiarity with various teaching and assessment skills needed to teach PGY(1) residents and ACGME competencies, and these clinical instructors also then subsequently apply these skills.",2011 Nov 24,"['Lee, Fa-Yauh', 'Yang, Ying-Ying', 'Hsu, Hui-Chi', 'Chuang, Chiao-Lin', 'Lee, Wei-Shin', 'Chang, Ching-Chih', 'Huang, Chia-Chang', 'Chen, Jaw-Wen', 'Cheng, Hao-Min', 'Jap, Tjin-Shing']",BMJ Open,,,False
254d6eaca1e97c257285000fbb96e9544dbee648,PMC,Clinical instructors' perception of a faculty development programme promoting postgraduate year-1 (PGY(1)) residents' ACGME six core competencies: a 2-year study,http://dx.doi.org/10.1136/bmjopen-2011-000200,PMC3225591,22116089,CC BY-NC,"OBJECTIVE: The six core competencies designated by Accreditation Council for Graduate Medical Education (ACGME) are essential for establishing a patient centre holistic medical system. The authors developed a faculty programme to promote the postgraduate year 1 (PGY(1)) resident, ACGME six core competencies. The study aims to assess the clinical instructors' perception, attitudes and subjective impression towards the various sessions of the ‘faculty development programme for teaching ACGME competencies.’ METHODS: During 2009 and 2010, 134 clinical instructors participated in the programme to establish their ability to teach and assess PGY(1) residents about ACGME competencies. RESULTS: The participants in the faculty development programme reported that the skills most often used while teaching were learnt during circuit and itinerant bedside, physical examination teaching, mini-clinical evaluation exercise (mini-CEX) evaluation demonstration, training workshop and videotapes of ‘how to teach ACGME competencies.’ Participants reported that circuit bedside teaching and mini-CEX evaluation demonstrations helped them in the interpersonal and communication skills domain, and that the itinerant teaching demonstrations helped them in the professionalism domain, while physical examination teaching and mini-CEX evaluation demonstrations helped them in the patients' care domain. Both the training workshop and videotape session increase familiarity with teaching and assessing skills. Participants who applied the skills learnt from the faculty development programme the most in their teaching and assessment came from internal medicine departments, were young attending physician and had experience as PGY(1) clinical instructors. CONCLUSIONS: According to the clinical instructors' response, our faculty development programme effectively increased their familiarity with various teaching and assessment skills needed to teach PGY(1) residents and ACGME competencies, and these clinical instructors also then subsequently apply these skills.",2011 Nov 24,"['Lee, Fa-Yauh', 'Yang, Ying-Ying', 'Hsu, Hui-Chi', 'Chuang, Chiao-Lin', 'Lee, Wei-Shin', 'Chang, Ching-Chih', 'Huang, Chia-Chang', 'Chen, Jaw-Wen', 'Cheng, Hao-Min', 'Jap, Tjin-Shing']",BMJ Open,,,False
f7ac35d7c3374eaaedab51c7d44d34ae738caf4a,PMC,The invasion of tobacco mosaic virus RNA induces endoplasmic reticulum stress-related autophagy in HeLa cells,http://dx.doi.org/10.1042/BSR20110069,PMC3225954,21729006,CC BY-NC,"The ability of human cells to defend against viruses originating from distant species has long been ignored. Owing to the pressure of natural evolution and human exploration, some of these viruses may be able to invade human beings. If their ‘fresh’ host had no defences, the viruses could cause a serious pandemic, as seen with HIV, SARS (severe acute respiratory syndrome) and avian influenza virus that originated from chimpanzees, the common palm civet and birds, respectively. It is unknown whether the human immune system could tolerate invasion with a plant virus. To model such an alien virus invasion, we chose TMV (tobacco mosaic virus) and used human epithelial carcinoma cells (HeLa cells) as its ‘fresh’ host. We established a reliable system for transfecting TMV-RNA into HeLa cells and found that TMV-RNA triggered autophagy in HeLa cells as shown by the appearance of autophagic vacuoles, the conversion of LC3-I (light chain protein 3-I) to LC3-II, the up-regulated expression of Beclin1 and the accumulation of TMV protein on autophagosomal membranes. We observed suspected TMV virions in HeLa cells by TEM (transmission electron microscopy). Furthermore, we found that TMV-RNA was translated into CP (coat protein) in the ER (endoplasmic reticulum) and that TMV-positive RNA translocated from the cytoplasm to the nucleolus. Finally, we detected greatly increased expression of GRP78 (78 kDa glucose-regulated protein), a typical marker of ERS (ER stress) and found that the formation of autophagosomes was closely related to the expanded ER membrane. Taken together, our data indicate that HeLa cells used ERS and ERS-related autophagy to defend against TMV-RNA.",2012 Apr 1,"['Li, Li', 'Wang, Li', 'Xiao, Ruijing', 'Zhu, Guoguo', 'Li, Yan', 'Liu, Changxuan', 'Yang, Ru', 'Tang, Zhiqing', 'Li, Jie', 'Huang, Wei', 'Chen, Lang', 'Zheng, Xiaoling', 'He, Yuling', 'Tan, Jinquan']",Biosci Rep,,,False
80a789fb3ed3279911f241585e315718b54c9a91,PMC,The invasion of tobacco mosaic virus RNA induces endoplasmic reticulum stress-related autophagy in HeLa cells,http://dx.doi.org/10.1042/BSR20110069,PMC3225954,21729006,CC BY-NC,"The ability of human cells to defend against viruses originating from distant species has long been ignored. Owing to the pressure of natural evolution and human exploration, some of these viruses may be able to invade human beings. If their ‘fresh’ host had no defences, the viruses could cause a serious pandemic, as seen with HIV, SARS (severe acute respiratory syndrome) and avian influenza virus that originated from chimpanzees, the common palm civet and birds, respectively. It is unknown whether the human immune system could tolerate invasion with a plant virus. To model such an alien virus invasion, we chose TMV (tobacco mosaic virus) and used human epithelial carcinoma cells (HeLa cells) as its ‘fresh’ host. We established a reliable system for transfecting TMV-RNA into HeLa cells and found that TMV-RNA triggered autophagy in HeLa cells as shown by the appearance of autophagic vacuoles, the conversion of LC3-I (light chain protein 3-I) to LC3-II, the up-regulated expression of Beclin1 and the accumulation of TMV protein on autophagosomal membranes. We observed suspected TMV virions in HeLa cells by TEM (transmission electron microscopy). Furthermore, we found that TMV-RNA was translated into CP (coat protein) in the ER (endoplasmic reticulum) and that TMV-positive RNA translocated from the cytoplasm to the nucleolus. Finally, we detected greatly increased expression of GRP78 (78 kDa glucose-regulated protein), a typical marker of ERS (ER stress) and found that the formation of autophagosomes was closely related to the expanded ER membrane. Taken together, our data indicate that HeLa cells used ERS and ERS-related autophagy to defend against TMV-RNA.",2012 Apr 1,"['Li, Li', 'Wang, Li', 'Xiao, Ruijing', 'Zhu, Guoguo', 'Li, Yan', 'Liu, Changxuan', 'Yang, Ru', 'Tang, Zhiqing', 'Li, Jie', 'Huang, Wei', 'Chen, Lang', 'Zheng, Xiaoling', 'He, Yuling', 'Tan, Jinquan']",Biosci Rep,,,True
14e7bfe37c331fdf83f54808418cae7129a653a0,PMC,The First Case of Feline Infectious Peritonitis-like Pyogranuloma in                     a Ferret Infected by Coronavirus in Japan,http://dx.doi.org/10.1293/tox.23.99,PMC3234644,22319227,CC BY-NC-ND,"A male ferret, which was purchased from abroad at 9 months of age, had shown significant weight loss starting at 13 months of age. The ferret subsequently showed decreasing motor activity and recumbency and was euthanized at 14 months of age. At necropsy, a white, quail egg-sized mass was found in the mesentery. Histopathologically, multifocal granulomas consisting of necrotic foci, macrophages, fibroblasts and plentiful fibrous connective tissues were observed in the mesenteric mass. Surrounding the granulomas, inflammatory cell infiltration consisting of neutrophils, lymphocytes and plasmacytes was observed diffusely and significantly. Immunohistochemistry revealed small numbers of macrophages around necrotic foci that were positively stained for anti-mouse feline coronavirus. Electron microscopically, the cytoplasm of the macrophages contained viral particles, which were identified as coronavirus. The histopathological features in this ferret were similar to those in cats with feline infectious peritonitis (FIP). This was the first case in ferrets in Japan.",2010 Jun 30,"['Michimae, Yoshiko', 'Mikami, Shin-ichi', 'Okimoto, Kazuo', 'Toyosawa, Kaoru', 'Matsumoto, Izumi', 'Kouchi, Mami', 'Koujitani, Takatoshi', 'Inoue, Tadashi', 'Seki, Takaki']",J Toxicol Pathol,,,True
894e9a681490af51667a059d727a9cce8dddbf7f,PMC,Complement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin,http://dx.doi.org/10.1128/mBio.00276-11,PMC3236064,22167226,CC BY-NC-SA,"Mannose-binding lectin (MBL) is a key soluble pathogen recognition protein of the innate immune system that binds specific mannose-containing glycans on the surfaces of microbial agents and initiates complement activation via the lectin pathway. Prior studies showed that MBL-dependent activation of the complement cascade neutralized insect cell-derived West Nile virus (WNV) in cell culture and restricted pathogenesis in mice. Here, we investigated the antiviral activity of MBL in infection by dengue virus (DENV), a related flavivirus. Using a panel of naïve sera from mouse strains deficient in different complement components, we showed that inhibition of infection by insect cell- and mammalian cell-derived DENV was primarily dependent on the lectin pathway. Human MBL also bound to DENV and neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. Experiments with human serum from naïve individuals with inherent variation in the levels of MBL in blood showed a direct correlation between the concentration of MBL and neutralization of DENV; samples with high levels of MBL in blood neutralized DENV more efficiently than those with lower levels. Our studies suggest that allelic variation of MBL in humans may impact complement-dependent control of DENV pathogenesis.",2011 Dec 13,"['Avirutnan, Panisadee', 'Hauhart, Richard E.', 'Marovich, Mary A.', 'Garred, Peter', 'Atkinson, John P.', 'Diamond, Michael S.']",mBio,,,True
c42949dc08e90ad09d1db9353ab925053fe6563d,PMC,The RNA polymerase activity of SARS-coronavirus nsp12 is primer dependent,http://dx.doi.org/10.1093/nar/gkr963,PMC3241673,,CC BY-NC,,2011 Nov 16,"['te Velthuis, Aartjan J. W.', 'Arnold, Jamie J.', 'Cameron, Craig E.', 'van den Worm, Sjoerd H. E.', 'Snijder, Eric J.']",Nucleic Acids Res,,,False
14b07f164039eddabc4f3932a873bcbccb2108f4,PMC,ViPR: an open bioinformatics database and analysis resource for virology research,http://dx.doi.org/10.1093/nar/gkr859,PMC3245011,22006842,CC BY-NC,"The Virus Pathogen Database and Analysis Resource (ViPR, www.ViPRbrc.org) is an integrated repository of data and analysis tools for multiple virus families, supported by the National Institute of Allergy and Infectious Diseases (NIAID) Bioinformatics Resource Centers (BRC) program. ViPR contains information for human pathogenic viruses belonging to the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Flaviviridae, Filoviridae, Hepeviridae, Herpesviridae, Paramyxoviridae, Picornaviridae, Poxviridae, Reoviridae, Rhabdoviridae and Togaviridae families, with plans to support additional virus families in the future. ViPR captures various types of information, including sequence records, gene and protein annotations, 3D protein structures, immune epitope locations, clinical and surveillance metadata and novel data derived from comparative genomics analysis. Analytical and visualization tools for metadata-driven statistical sequence analysis, multiple sequence alignment, phylogenetic tree construction, BLAST comparison and sequence variation determination are also provided. Data filtering and analysis workflows can be combined and the results saved in personal ‘Workbenches’ for future use. ViPR tools and data are available without charge as a service to the virology research community to help facilitate the development of diagnostics, prophylactics and therapeutics for priority pathogens and other viruses.",2012 Jan 17,"['Pickett, Brett E.', 'Sadat, Eva L.', 'Zhang, Yun', 'Noronha, Jyothi M.', 'Squires, R. Burke', 'Hunt, Victoria', 'Liu, Mengya', 'Kumar, Sanjeev', 'Zaremba, Sam', 'Gu, Zhiping', 'Zhou, Liwei', 'Larson, Christopher N.', 'Dietrich, Jonathan', 'Klem, Edward B.', 'Scheuermann, Richard H.']",Nucleic Acids Res,,,True
6edbfac15ca59eb0e18859543190088f7a52112e,PMC,VIRsiRNAdb: a curated database of experimentally validated viral siRNA/shRNA,http://dx.doi.org/10.1093/nar/gkr1147,PMC3245049,22139916,CC BY-NC,"RNAi technology has been emerging as a potential modality to inhibit viruses during past decade. In literature a few siRNA databases have been reported that focus on targeting human and mammalian genes but experimentally validated viral siRNA databases are lacking. We have developed VIRsiRNAdb, a manually curated database having comprehensive details of 1358 siRNA/shRNA targeting viral genome regions. Further, wherever available, information regarding alternative efficacies of above 300 siRNAs derived from different assays has also been incorporated. Important fields included in the database are siRNA sequence, virus subtype, target genome region, cell type, target object, experimental assay, efficacy, off-target and siRNA matching with reference viral sequences. Database also provides the users with facilities of advance search, browsing, data submission, linking to external databases and useful siRNA analysis tools especially siTarAlign which align the siRNA with reference viral genomes or user defined sequences. VIRsiRNAdb contains extensive details of siRNA/shRNA targeting 42 important human viruses including influenza virus, hepatitis B virus, HPV and SARS Corona virus. VIRsiRNAdb would prove useful for researchers in picking up the best viral siRNA for antiviral therapeutics development and also for developing better viral siRNA design tools. The database is freely available at http://crdd.osdd.net/servers/virsirnadb.",2012 Jan 1,"['Thakur, Nishant', 'Qureshi, Abid', 'Kumar, Manoj']",Nucleic Acids Res,,,True
2a17719f2c1d211a651060441bda8bc1c052e2aa,PMC,ELM—the database of eukaryotic linear motifs,http://dx.doi.org/10.1093/nar/gkr1064,PMC3245074,22110040,CC BY-NC,"Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization. Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally. The Eukaryotic Linear Motif (ELM) resource at http://elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences. The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes. Several older motif class entries have been also revisited, improving annotation and adding novel instances. Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data. The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instances.",2012 Jan 21,"['Dinkel, Holger', 'Michael, Sushama', 'Weatheritt, Robert J.', 'Davey, Norman E.', 'Van Roey, Kim', 'Altenberg, Brigitte', 'Toedt, Grischa', 'Uyar, Bora', 'Seiler, Markus', 'Budd, Aidan', 'Jödicke, Lisa', 'Dammert, Marcel A.', 'Schroeter, Christian', 'Hammer, Maria', 'Schmidt, Tobias', 'Jehl, Peter', 'McGuigan, Caroline', 'Dymecka, Magdalena', 'Chica, Claudia', 'Luck, Katja', 'Via, Allegra', 'Chatr-aryamontri, Andrew', 'Haslam, Niall', 'Grebnev, Gleb', 'Edwards, Richard J.', 'Steinmetz, Michel O.', 'Meiselbach, Heike', 'Diella, Francesca', 'Gibson, Toby J.']",Nucleic Acids Res,,,True
6fa649c67f566b9bcd0450e3a9614cbd6fddf74c,PMC,Microarrays for Pathogen Detection and Analysis,http://dx.doi.org/10.1093/bfgp/elr027,PMC3245552,21930658,CC BY-NC,"DNA microarrays have emerged as a viable platform for detection of pathogenic organisms in clinical and environmental samples. These microbial detection arrays occupy a middle ground between low cost, narrowly focused assays such as multiplex PCR and more expensive, broad-spectrum technologies like high-throughput sequencing. While pathogen detection arrays have been used primarily in a research context, several groups are aggressively working to develop arrays for clinical diagnostics, food safety testing, environmental monitoring and biodefense. Statistical algorithms that can analyze data from microbial detection arrays and provide easily interpretable results are absolutely required in order for these efforts to succeed. In this article, we will review the most promising array designs and analysis algorithms that have been developed to date, comparing their strengths and weaknesses for pathogen detection and discovery.",2011 Nov 19,"McLoughlin, Kevin S.",Brief Funct Genomics,,,True
721b3e6ae8af24a4f625540bbb6e2c02fb77b491,PMC,mRNA pseudoknot structures can act as ribosomal roadblocks,http://dx.doi.org/10.1093/nar/gkr686,PMC3245918,21908395,CC BY-NC,"Several viruses utilize programmed ribosomal frameshifting mediated by mRNA pseudoknots in combination with a slippery sequence to produce a well defined stochiometric ratio of the upstream encoded to the downstream-encoded protein. A correlation between the mechanical strength of mRNA pseudoknots and frameshifting efficiency has previously been found; however, the physical mechanism behind frameshifting still remains to be fully understood. In this study, we utilized synthetic sequences predicted to form mRNA pseudoknot-like structures. Surprisingly, the structures predicted to be strongest lead only to limited frameshifting. Two-dimensional gel electrophoresis of pulse labelled proteins revealed that a significant fraction of the ribosomes were frameshifted but unable to pass the pseudoknot-like structures. Hence, pseudoknots can act as ribosomal roadblocks, prohibiting a significant fraction of the frameshifted ribosomes from reaching the downstream stop codon. The stronger the pseudoknot the larger the frameshifting efficiency and the larger its roadblocking effect. The maximal amount of full-length frameshifted product is produced from a structure where those two effects are balanced. Taking ribosomal roadblocking into account is a prerequisite for formulating correct frameshifting hypotheses.",2012 Jan 8,"['Tholstrup, Jesper', 'Oddershede, Lene B.', 'Sørensen, Michael A.']",Nucleic Acids Res,,,True
c031da739085e21f3acac50ca0fa90c443466894,PMC,mRNA pseudoknot structures can act as ribosomal roadblocks,http://dx.doi.org/10.1093/nar/gkr686,PMC3245918,21908395,CC BY-NC,"Several viruses utilize programmed ribosomal frameshifting mediated by mRNA pseudoknots in combination with a slippery sequence to produce a well defined stochiometric ratio of the upstream encoded to the downstream-encoded protein. A correlation between the mechanical strength of mRNA pseudoknots and frameshifting efficiency has previously been found; however, the physical mechanism behind frameshifting still remains to be fully understood. In this study, we utilized synthetic sequences predicted to form mRNA pseudoknot-like structures. Surprisingly, the structures predicted to be strongest lead only to limited frameshifting. Two-dimensional gel electrophoresis of pulse labelled proteins revealed that a significant fraction of the ribosomes were frameshifted but unable to pass the pseudoknot-like structures. Hence, pseudoknots can act as ribosomal roadblocks, prohibiting a significant fraction of the frameshifted ribosomes from reaching the downstream stop codon. The stronger the pseudoknot the larger the frameshifting efficiency and the larger its roadblocking effect. The maximal amount of full-length frameshifted product is produced from a structure where those two effects are balanced. Taking ribosomal roadblocking into account is a prerequisite for formulating correct frameshifting hypotheses.",2012 Jan 8,"['Tholstrup, Jesper', 'Oddershede, Lene B.', 'Sørensen, Michael A.']",Nucleic Acids Res,,,False
df5763298a47b06f4efcd3ae836e0d0a487d1d97,PMC,The cell biology of receptor-mediated virus entry,http://dx.doi.org/10.1083/jcb.201108131,PMC3246895,22123832,CC BY-NC-SA,"The cell imposes multiple barriers to virus entry. However, viruses exploit fundamental cellular processes to gain entry to cells and deliver their genetic cargo. Virus entry pathways are largely defined by the interactions between virus particles and their receptors at the cell surface. These interactions determine the mechanisms of virus attachment, uptake, intracellular trafficking, and, ultimately, penetration to the cytosol. Elucidating the complex interplay between viruses and their receptors is necessary for a full understanding of how these remarkable agents invade their cellular hosts.",2011 Dec 26,"['Grove, Joe', 'Marsh, Mark']",J Cell Biol,,,True
c6be64927ed61a5ec6ad9e947934aea286e2f46e,PMC,Uterine adenocarcinoma with feline leukemia virus infection,http://dx.doi.org/10.5625/lar.2011.27.4.347,PMC3251767,22232645,CC BY-NC,"Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have been poorly characterized to date. In this study, we describe a uterine adenocarcinoma in a Persian cat with feline leukemia virus infection. At the time of presentation, the cat, a female Persian chinchilla, was 2 years old. The cat underwent surgical ovariohystectomy. A cross-section of the uterine wall revealed a thickened uterine horn. The cat tested positive for feline leukemia virus as detected by polymerase chain reaction. Histopathological examination revealed uterine adenocarcinoma that had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions. Based on the histopathological findings, this case was diagnosed as a uterine adenocarcinoma with abdominal metastasis. To the best of our knowledge, this is the first report of a uterine adenocarcinoma with feline leukemia virus infection.",2011 Dec 19,"['Cho, Sung-Jin', 'Lee, Hyun-A', 'Hong, Sunhwa', 'Kim, Okjin']",Lab Anim Res,,,True
fa2ab10f1041d2bdf77688448044ce72dfc74eca,PMC,Evaluation of the Seeplex® Meningitis ACE Detection Kit for the Detection of 12 Common Bacterial and Viral Pathogens of Acute Meningitis,http://dx.doi.org/10.3343/alm.2012.32.1.44,PMC3255489,22259778,CC BY-NC,"BACKGROUND: Bacterial meningitis is an infectious disease with high rates of mortality and high frequency of severe sequelae. Early identification of causative bacterial and viral pathogens is important for prompt and proper treatment of meningitis and for prevention of life-threatening clinical outcomes. In the present study, we evaluated the value of the Seeplex Meningitis ACE Detection kit (Seegene Inc., Korea), a newly developed multiplex PCR kit employing dual priming oligonucleotide methods, for diagnosing acute meningitis. METHODS: Analytical sensitivity of the kit was studied using reference strains for each pathogen targeted by the kit, while it's analytical specificity was studied using the human genome DNA and 58 clinically well-identified reference strains. For clinical validation experiment, we used 27 control cerebrospinal fluid (CSF) samples and 78 clinical CSF samples collected from patients at the time of diagnosis of acute meningitis. RESULTS: The lower detection limits ranged from 10(1) copies/µL to 5×10(1) copies/µL for the 12 viral and bacterial pathogens targeted. No cross-reaction was observed. In the validation study, high detection rate of 56.4% was obtained. None of the control samples tested positive, i.e., false-positive results were absent. CONCLUSIONS: The Seeplex Meningitis ACE Detection kit showed high sensitivity, specificity, and detection rate for the identification of pathogens in clinical CSF samples. This kit may be useful for rapid identification of important acute meningitis-causing pathogens.",2012 Jan 20,"['Shin, So Youn', 'Kwon, Kye Chul', 'Park, Jong Woo', 'Kim, Ji Myung', 'Shin, So Young', 'Koo, Sun Hoe']",Ann Lab Med,,,True
d383ffc5115974fdaa97c744e2a579960a6c7cb2,PMC,Inhaled Nitric Oxide Therapy Fails to Improve Outcome in Experimental Severe Influenza,http://dx.doi.org/10.7150/ijms.3880,PMC3258558,22253563,CC BY-NC-ND,"In vitro, nitric oxide (NO) has been shown to have antimicrobial activity against a wide range of viruses, including influenza A virus. Therefore, we hypothesized that inhaled nitric oxide (iNO) would increase survival in vivo by reducing the viral load in C57Bl/6 mice infected with a lethal dose of influenza A/WSN/33 (H1N1; WSN/33) virus. NO was delivered to influenza-infected mice either continuously or intermittently at 80 or 160 ppm, respectively, using both prophylactic and post-infection treatment strategies. Murine survival and weight loss were assessed, and lung viral load was quantified via plaque assay. Here, we report that iNO administered prophylactically or post-influenza infection failed to improve survival of infected mice. No difference in lung viral load was observed between experimental groups. Although NO has antiviral activity against influenza A virus in vitro, iNO therapy provided no apparent benefit when used for treatment of influenza A virus infection in vivo.",2012 Jan 13,"['Darwish, Ilyse', 'Miller, Chris', 'Kain, Kevin C.', 'Liles, W. Conrad']",Int J Med Sci,,,True
20dd62d0387e8b4231d67af2eaf757767492656e,PMC,Interleukin-18 expression and the response to treatment in patients with psoriasis,http://dx.doi.org/10.5114/aoms.2011.24144,PMC3258774,22291810,CC BY-NC-ND,"INTRODUCTION: The aim of the study was to demonstrate interleukin-18 (IL-18) expression in keratinocytes from psoriatic lesions in comparison to keratinocytes from uninvolved skin and to study the change of expression after therapeutic interventions. MATERIAL AND METHODS: This study included 16 patients of different clinical subtypes of psoriasis. Interleukin-18 gene expression analysis was performed using real time quantitative PCR. Three biopsies were obtained from each patient. Two were taken from the lesional psoriatic skin and from uninvolved skin before starting treatment. A third lesional skin biopsy was taken at the end of 2 months of treatment. The treatment was in the form of topical steroids or oral systemic methotrexate. RESULTS: Of all 16 studied patients, significantly increased IL-18 expression was noted in keratinocytes from psoriatic lesions before and after treatment when compared to keratinocytes from uninvolved skin (p = 0.001 and p = 0.002 respectively). The IL-18 expression in the skin lesions after treatment was significantly lower than lesional skin before treatment (p = 0.023). In psoriatic skin lesions of all studied patients IL-18 expression was significantly correlated with disease duration (r = 0.40 and p = 0.01) and clinical severity of psoriasis (r = 0.72 and p = 0.001). CONCLUSIONS: Increased IL-18 expression in keratinocytes from psoriatic lesions of our patients and its correlation with disease duration and severity supported the concept of psoriasis as a T cell mediated autoimmune disease. This could establish therapeutic and preventive approaches for psoriasis that ultimately lead to improved outcomes for patients.",2011 Aug 2,"['Rasmy, Hanaa', 'Mikhael, Nancy', 'Ismail, Somaia']",Arch Med Sci,,,True
8c8c5fb760997ded36fe4ae8fc77103ec66f9d14,PMC,Development and Applications of VSV Vectors Based on Cell Tropism,http://dx.doi.org/10.3389/fmicb.2011.00272,PMC3260743,22279443,CC BY-NC,"Viral vectors have been available in various fields such as medical and biological research or gene therapy applications. Targeting vectors pseudotyped with distinct viral envelope proteins that influence cell tropism and transfection efficiency are useful tools not only for examining entry mechanisms or cell tropisms but also for vaccine vector development. Vesicular stomatitis virus (VSV) is an excellent candidate for development as a pseudotype vector. A recombinant VSV lacking its own envelope (G) gene has been used to produce a pseudotype or recombinant VSV possessing the envelope proteins of heterologous viruses. These viruses possess a reporter gene instead of a VSV G gene in their genome, and therefore it is easy to evaluate their infectivity in the study of viral entry, including identification of viral receptors. Furthermore, advantage can be taken of a property of the pseudotype VSV, which is competence for single-round infection, in handling many different viruses that are either difficult to amplify in cultured cells or animals or that require specialized containment facilities. Here we describe procedures for producing pseudotype or recombinant VSVs and a few of the more prominent examples from envelope viruses, such as hepatitis C virus, Japanese encephalitis virus, baculovirus, and hemorrhagic fever viruses.",2012 Jan 18,"['Tani, Hideki', 'Morikawa, Shigeru', 'Matsuura, Yoshiharu']",Front Microbiol,,,True
43fa3923d6ba1d04fb5b0419f617b8c2fbc2f268,PMC,International Society for Disease Surveillance Conference 2011: Building the Future of Public Health Surveillance: Building the Future of Public Health Surveillance,http://dx.doi.org/10.3402/ehtj.v4i0.11702,PMC3261719,24149043,CC BY-NC,,2011 Dec 6,"['Neill, Daniel B.', 'Soetebier, Karl A.']",Emerg Health Threats J,,,True
d1268a2b5aa5778f15fbd10152728dc936a6809e,PMC,Unraveling the structural complexity in a single-stranded RNA tail: implications for efficient ligand binding in the prequeuosine riboswitch,http://dx.doi.org/10.1093/nar/gkr833,PMC3273816,22009676,CC BY-NC,"Single-stranded RNAs (ssRNAs) are ubiquitous RNA elements that serve diverse functional roles. Much of our understanding of ssRNA conformational behavior is limited to structures in which ssRNA directly engages in tertiary interactions or is recognized by proteins. Little is known about the structural and dynamic behavior of free ssRNAs at atomic resolution. Here, we report the collaborative application of nuclear magnetic resonance (NMR) and replica exchange molecular dynamics (REMD) simulations to characterize the 12 nt ssRNA tail derived from the prequeuosine riboswitch. NMR carbon spin relaxation data and residual dipolar coupling measurements reveal a flexible yet stacked core adopting an A-form-like conformation, with the level of order decreasing toward the terminal ends. An A-to-C mutation within the polyadenine tract alters the observed dynamics consistent with the introduction of a dynamic kink. Pre-ordering of the tail may increase the efficacy of ligand binding above that achieved by a random-coil ssRNA. The REMD simulations recapitulate important trends in the NMR data, but suggest more internal motions than inferred from the NMR analysis. Our study unmasks a previously unappreciated level of complexity in ssRNA, which we believe will also serve as an excellent model system for testing and developing computational force fields.",2012 Feb 18,"['Eichhorn, Catherine D.', 'Feng, Jun', 'Suddala, Krishna C.', 'Walter, Nils G.', 'Brooks, Charles L.', 'Al-Hashimi, Hashim M.']",Nucleic Acids Res,,,True
fd91f413c64ec2c83c4bc7b611e41040ea3d8417,PMC,Unraveling the structural complexity in a single-stranded RNA tail: implications for efficient ligand binding in the prequeuosine riboswitch,http://dx.doi.org/10.1093/nar/gkr833,PMC3273816,22009676,CC BY-NC,"Single-stranded RNAs (ssRNAs) are ubiquitous RNA elements that serve diverse functional roles. Much of our understanding of ssRNA conformational behavior is limited to structures in which ssRNA directly engages in tertiary interactions or is recognized by proteins. Little is known about the structural and dynamic behavior of free ssRNAs at atomic resolution. Here, we report the collaborative application of nuclear magnetic resonance (NMR) and replica exchange molecular dynamics (REMD) simulations to characterize the 12 nt ssRNA tail derived from the prequeuosine riboswitch. NMR carbon spin relaxation data and residual dipolar coupling measurements reveal a flexible yet stacked core adopting an A-form-like conformation, with the level of order decreasing toward the terminal ends. An A-to-C mutation within the polyadenine tract alters the observed dynamics consistent with the introduction of a dynamic kink. Pre-ordering of the tail may increase the efficacy of ligand binding above that achieved by a random-coil ssRNA. The REMD simulations recapitulate important trends in the NMR data, but suggest more internal motions than inferred from the NMR analysis. Our study unmasks a previously unappreciated level of complexity in ssRNA, which we believe will also serve as an excellent model system for testing and developing computational force fields.",2012 Feb 18,"['Eichhorn, Catherine D.', 'Feng, Jun', 'Suddala, Krishna C.', 'Walter, Nils G.', 'Brooks, Charles L.', 'Al-Hashimi, Hashim M.']",Nucleic Acids Res,,,False
915bbf3af94c8bb413b496b0d4d7f88a1ed7d7bb,PMC,Infectious diseases in children and adolescents in the Republic of Korea; Past & recent status,http://dx.doi.org/10.3345/kjp.2011.54.12.489,PMC3274655,22323905,CC BY-NC,"Compared to the past decades, in recent decades, environmental and hygienic conditions in the Republic of Korea have improved along with socioeconomic developments, and the incidence of most infectious diseases, especially vaccine-preventable diseases, has greatly decreased due to active immunization with the developed level of health care. However, the incidence of some diseases has been increasing, and new diseases have been emerging. To cope with such changes actively, the government put the ""Law for Control and Prevention of Infectious Diseases"" into effect; this law was entirely revised on December 30, 2010. In this report, I review the past and recent status of infectious diseases in the Republic of Korea, following the introduction of this law, on the basis of data in the ""National Notifiable Disease Surveillance System"", which had been accumulated between the years 1960 and 2010.",2011 Dec 31,"Kim, Jong-Hyun",Korean J Pediatr,,,True
a2c1a9a13829fc83999db461322319bda6c81530,PMC,Filovirus Tropism: Cellular Molecules for Viral Entry,http://dx.doi.org/10.3389/fmicb.2012.00034,PMC3277274,22363323,CC BY-NC,"In human and non-human primates, filoviruses (Ebola and Marburg viruses) cause severe hemorrhagic fever. Recently, other animals such as pigs and some species of fruit bats have also been shown to be susceptible to these viruses. While having a preference for some cell types such as hepatocytes, endothelial cells, dendritic cells, monocytes, and macrophages, filoviruses are known to be pantropic in infection of primates. The envelope glycoprotein (GP) is responsible for both receptor binding and fusion of the virus envelope with the host cell membrane. It has been demonstrated that filovirus GP interacts with multiple molecules for entry into host cells, whereas none of the cellular molecules so far identified as a receptor/co-receptor fully explains filovirus tissue tropism and host range. Available data suggest that the mucin-like region (MLR) on GP plays an important role in attachment to the preferred target cells, whose infection is likely involved in filovirus pathogenesis, whereas the MLR is not essential for the fundamental function of the GP in viral entry into cells in vitro. Further studies elucidating the mechanisms of cellular entry of filoviruses may shed light on the development of strategies for prophylaxis and treatment of Ebola and Marburg hemorrhagic fevers.",2012 Feb 6,"Takada, Ayato",Front Microbiol,,,True
7321a41ee2054c07a18ede4e04a420621cb33087,PMC,Human bocavirus infections in hospitalized Greek children,http://dx.doi.org/10.5114/aoms.2010.13515,PMC3278951,22371728,CC BY-NC-ND,"INTRODUCTION: The epidemiology of human bocavirus (HBoV) infections has not been described in Greece, a south-eastern European country. To define the epidemiological profile and the clinical characteristics associated with HBoV infection in a population of children hospitalized with respiratory tract infection. MATERIAL AND METHODS: During a one-year period throat swab samples were collected from 370 previously healthy children, aged 14 days to 13 years, admitted to two different paediatric wards because of respiratory tract infection. Samples were tested for HBoV by PCR amplifying a part of the NS1 gene. RESULTS: Human bocavirus was detected in 12 children (3.2%). Four of the 12 cases were co-infections, 3 of them with influenza A and 1 with coronavirus OC43. Cases were observed only during the cold months. The mean age of children was 1.8 years (range 2 months to 4 years). The most common symptoms were fever, cough and various degrees of respiratory distress. All children were clinically diagnosed as having lower respiratory tract infections, mainly pneumonia and acute laryngotracheobronchitis, and recovered uneventfully. CONCLUSIONS: HBoV infections occur in Greece mostly among very young children. They accounted for 3.2% of children hospitalized with acute respiratory disease. Cases were observed only in late autumn to early spring.",2010 Mar 1,"['Haidopoulou, Katerina', 'Goutaki, Myrofora', 'Damianidou, Lambrini', 'Eboriadou, Maria', 'Antoniadis, Antonis', 'Papa, Anna']",Arch Med Sci,,,True
93df1925c1aa0cf7e721ebcbaed2d261c032d925,PMC,"Kawasaki Disease: Laboratory Findings and an Immunopathogenesis on the Premise of a ""Protein Homeostasis System""",http://dx.doi.org/10.3349/ymj.2012.53.2.262,PMC3282974,22318812,CC BY-NC,"Kawasaki disease (KD) is a self-limited systemic inflammatory illness, and coronary artery lesions (CALs) are a major complication determining the prognosis of the disease. Epidemiologic studies in Asian children suggest that the etiologic agent(s) of KD may be associated with environmental changes. Laboratory findings are useful for the diagnosis of incomplete KD, and they can guide the next-step in treatment of initial intravenous immunoglobulin non-responders. CALs seem to develop in the early stages of the disease before a peak in inflammation. Therefore early treatment, before the peak in inflammation, is mandatory to reduce the risk of CAL progression and severity of CALs. The immunopathogenesis of KD is more likely that of acute rheumatic fever than scarlet fever. A hypothetical pathogenesis of KD is proposed under the premise of a ""protein homeostasis system""; where innate and adaptive immune cells control pathogenic proteins that are toxic to host cells at a molecular level. After an infection of unknown KD pathogen(s), the pathogenic proteins produced from an unknown focus, spread and bind to endothelial cells of coronary arteries as main target cells. To control the action of pathogenic proteins and/or substances from the injured cells, immune cells are activated. Initially, non-specific T cells and non-specific antibodies are involved in this reaction, while hyperactivated immune cells produce various cytokines, leading to a cytokine imbalance associated with further endothelial cell injury. After the emergence of specific T cells and specific antibodies against the pathogenic proteins, tissue injury ceases and a repair reaction begins with the immune cells.",2012 Mar 1,"['Lee, Kyung-Yil', 'Rhim, Jung-Woo', 'Kang, Jin-Han']",Yonsei Med J,,,True
51485c1b5e3ce7050422a81c6a16ed00faa768fd,PMC,Hyponatraemia in cases of children with pneumonia,http://dx.doi.org/10.5114/aoms.2010.14471,PMC3284074,22371803,CC BY-NC-ND,"INTRODUCTION: Hyponatraemia is the most common electrolyte imbalance seen in clinical practice, and a common laboratory finding in children with community-acquired pneumonia (CAP). This study aimed to identify the incidence of hyponatraemia in cases of CAP, to find predictive tools in order to classify the severity and outcome of CAP and to explore possible differences of clinical importance between the two sexes. MATERIAL AND METHODS: The medical files of 54 children (66.4% males), 4.67 ±2.88 years old, were retro-prospectively reviewed. RESULTS: 35/54 (64.8%) children with pneumonia had normal values of sodium at admission, 18/54 (33.3%) had mild hyponatraemia and 1 child (1.9%) moderate hyponatraemia. Increased heart rhythm and tachypnoea at admission were correlated with lower values of sodium (z= −2.664, p = 0.007 and z = −1.705, p = 0.089 respectively). No differences were found between the two sexes concerning the characteristics of pneumonia or the range of sodium in serum at admission. A correlation was found between sodium admission values and: a) C-reactive protein (p = 0.000), and b) leukocyte count (p = 0.006). Sedimentation rate (p = 0.021) was also considered as a possible risk factor affecting the value of sodium at admission to hospital. Finally, a negative association was also observed between the degree of hyponatraemia and the duration of hospitalization (z = −3.398, p = 0.001). CONCLUSIONS: Although studies in larger population groups are needed, in our study increased heart rhythm, tachypnoea, leucocyte count, C-reactive protein, and also erythrocyte sedimentation rate could be considered as possible risk factors influencing the degree of hyponatraemia, and thus the outcome of hospitalized children with CAP.",2010 Aug 30,"['Sakellaropoulou, Afroditi', 'Hatzistilianou, Maria', 'Eboriadou, Maria', 'Athanasiadou-Piperopoulou, Fanni']",Arch Med Sci,,,True
b7d7db5b12584c5fab0c2244a27d0653d8a59f7d,PMC,Mouse Hepatitis Virus Receptor as a Determinant of the Mouse Susceptibility to MHV Infection,http://dx.doi.org/10.3389/fmicb.2012.00068,PMC3285771,22375141,CC BY-NC,"In this review, we report that the receptor of mouse hepatitis virus (MHV), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), is an important determinant of mouse susceptibility to MHV infection. This finding was revealed by using mouse strains with two different allelic forms of the MHV receptor, Ceacam1a and Ceacam1b. Although previous studies indicated that susceptibility is determined by a single gene, Ceacam1, our recent work in gene-replaced mice with chimeric Ceacam1 pointed toward the involvement of other host factors (genes) in the susceptibility. Studies on mouse susceptibility to MHV, as well as the factors involved in their susceptibility, are overviewed.",2012 Feb 24,"['Taguchi, Fumihiro', 'Hirai-Yuki, Asuka']",Front Microbiol,,,True
d99acb4e99be7852aa61a688c9fbd38d44b5a252,PMC,Evaluation of Measles Vaccine Virus as a Vector to Deliver Respiratory Syncytial Virus Fusion Protein or Epstein-Barr Virus Glycoprotein gp350,http://dx.doi.org/10.2174/1874357901206010012,PMC3286841,22383906,CC BY-NC,"Live attenuated recombinant measles vaccine virus (MV) Edmonston-Zagreb (EZ) strain was evaluated as a viral vector to express the ectodomains of fusion protein of respiratory syncytial virus (RSV F) or glycoprotein 350 of Epstein-Barr virus (EBV gp350) as candidate vaccines for prophylaxis of RSV and EBV. The glycoprotein gene was inserted at the 1(st) or the 3(rd) position of the measles virus genome and the recombinant viruses were generated. Insertion of the foreign gene at the 3(rd) position had a minimal impact on viral replication in vitro. RSV F or EBV gp350 protein was secreted from infected cells. In cotton rats, EZ-RSV F and EZ-EBV gp350 induced MV- and insert-specific antibody responses. In addition, both vaccines also induced insert specific interferon gamma (IFN-γ) secreting T cell response. EZ-RSV F protected cotton rats from pulmonary replication of RSV A2 challenge infection. In rhesus macaques, although both EZ-RSV F and EZ-EBV gp350 induced MV specific neutralizing antibody responses, only RSV F specific antibody response was detected. Thus, the immunogenicity of the foreign antigens delivered by measles vaccine virus is dependent on the nature of the insert and the animal models used for vaccine evaluation.",2012 Feb 16,"['Mok, Hoyin', 'Cheng, Xing', 'Xu, Qi', 'Zengel, James R', 'Parhy, Bandita', 'Zhao, Jackie', 'Wang, C. Kathy', 'Jin, Hong']",Open Virol J,,,True
24df3883c547f5976077bc7a924eec9ae8fa9e71,PMC,The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension,http://dx.doi.org/10.1093/nar/gkr893,PMC3287201,22039154,CC BY-NC,"Uniquely among RNA viruses, replication of the ∼30-kb SARS-coronavirus genome is believed to involve two RNA-dependent RNA polymerase (RdRp) activities. The first is primer-dependent and associated with the 106-kDa non-structural protein 12 (nsp12), whereas the second is catalysed by the 22-kDa nsp8. This latter enzyme is capable of de novo initiation and has been proposed to operate as a primase. Interestingly, this protein has only been crystallized together with the 10-kDa nsp7, forming a hexadecameric, dsRNA-encircling ring structure [i.e. nsp(7+8), consisting of 8 copies of both nsps]. To better understand the implications of these structural characteristics for nsp8-driven RNA synthesis, we studied the prerequisites for the formation of the nsp(7+8) complex and its polymerase activity. We found that in particular the exposure of nsp8's natural N-terminal residue was paramount for both the protein's ability to associate with nsp7 and for boosting its RdRp activity. Moreover, this ‘improved’ recombinant nsp8 was capable of extending primed RNA templates, a property that had gone unnoticed thus far. The latter activity is, however, ∼20-fold weaker than that of the primer-dependent nsp12-RdRp at equal monomer concentrations. Finally, site-directed mutagenesis of conserved D/ExD/E motifs was employed to identify residues crucial for nsp(7+8) RdRp activity.",2012 Feb 29,"['te Velthuis, Aartjan J.W.', 'van den Worm, Sjoerd H. E.', 'Snijder, Eric J.']",Nucleic Acids Res,,,True
10a0017e5f36b42e9f2e80d4481b16eb847bb4da,PMC,The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension,http://dx.doi.org/10.1093/nar/gkr893,PMC3287201,22039154,CC BY-NC,"Uniquely among RNA viruses, replication of the ∼30-kb SARS-coronavirus genome is believed to involve two RNA-dependent RNA polymerase (RdRp) activities. The first is primer-dependent and associated with the 106-kDa non-structural protein 12 (nsp12), whereas the second is catalysed by the 22-kDa nsp8. This latter enzyme is capable of de novo initiation and has been proposed to operate as a primase. Interestingly, this protein has only been crystallized together with the 10-kDa nsp7, forming a hexadecameric, dsRNA-encircling ring structure [i.e. nsp(7+8), consisting of 8 copies of both nsps]. To better understand the implications of these structural characteristics for nsp8-driven RNA synthesis, we studied the prerequisites for the formation of the nsp(7+8) complex and its polymerase activity. We found that in particular the exposure of nsp8's natural N-terminal residue was paramount for both the protein's ability to associate with nsp7 and for boosting its RdRp activity. Moreover, this ‘improved’ recombinant nsp8 was capable of extending primed RNA templates, a property that had gone unnoticed thus far. The latter activity is, however, ∼20-fold weaker than that of the primer-dependent nsp12-RdRp at equal monomer concentrations. Finally, site-directed mutagenesis of conserved D/ExD/E motifs was employed to identify residues crucial for nsp(7+8) RdRp activity.",2012 Feb 29,"['te Velthuis, Aartjan J.W.', 'van den Worm, Sjoerd H. E.', 'Snijder, Eric J.']",Nucleic Acids Res,,,False
c28ae565308bfabbd784a23fa065a59a49d8cfc3,PMC,Morbillivirus Receptors and Tropism: Multiple Pathways for Infection,http://dx.doi.org/10.3389/fmicb.2012.00075,PMC3290766,22403577,CC BY-NC,"Morbilliviruses, which include measles virus (MeV), canine distemper virus, and rinderpest virus, are among the most important pathogens in their respective hosts and cause severe syndromes. Morbilliviruses are enveloped viruses with two envelope proteins, one of which is hemagglutinin (H) protein, which plays a role in binding to cellular receptors. During morbillivirus infection, the virus initially targets lymphoid cells and replicates efficiently in the lymph nodes. The principal cellular receptor for morbillivirus is signaling lymphocyte activation molecule (SLAM, also called CD150), which is exclusively expressed on immune cells. This feature reflects the strong lymphoid cell tropism and viral spread in the infected body. Morbillivirus infection, however, affects various tissues in the body, including the lung, kidney, gastrointestinal tract, vascular endothelium, and brain. Thus, other receptors for morbilliviruses in addition to SLAM might exist. Recently, nectin-4 has been identified as a novel epithelial cell receptor for MeV. The expression of nectin-4 is localized to polarized epithelial cells, and this localization supports the notion of cell tropism since MeV also grows well in the epithelial cells of the respiratory tract. Although two major receptors for lymphoid and epithelial cells in natural infection have been identified, morbillivirus can still infect many other types of cells with low infectivity, suggesting the existence of inefficient but ubiquitously expressed receptors. We have identified other molecules that are implicated in morbillivirus infection of SLAM-negative cells by alternative mechanisms. These findings indicate that morbillivirus utilizes multiple pathways for establishment of infection. These studies will advance our understanding of morbillivirus tropism and pathogenesis.",2012 Mar 1,"['Sato, Hiroki', 'Yoneda, Misako', 'Honda, Tomoyuki', 'Kai, Chieko']",Front Microbiol,,,True
c042a8ca113beaec285ea086b0d1722eb838115f,PMC,Interleukin-18 expression and the response to treatment in patients with psoriasis,http://dx.doi.org/10.5114/aoms.2010.19309,PMC3302712,22427774,CC BY-NC-ND,INTRODUCTION: The aim of the study was to demonstrate Interleukin-18 (IL-18) expression in keratinocytes from psoriatic lesions in comparison to keratinocytes from uninvolved skin and to study the change of expression after therapeutic interventions. MATERIAL AND METHODS: This study included 16 patients of different clinical subtypes of psoriasis. IL-18 gene expression analysis was performed using real-time quantitative PCR. Three biopsies were obtained from each patient. Two were taken from the lesional psoriatic skin and from uninvolved skin before starting treatment. A third lesional skin biopsy was taken at the end of two months' treatment course. The treatment was in the form of topical steroids or oral systemic methotrexate. RESULTS: Of all 16 studied patients significantly increased IL-18 expression was noted in keratinocytes from psoriatic lesions before and after treatment when compared to keratinocytes from uninvolved skin (P = 0.001 and 0.002 respectively). The IL-18 expression in the skin lesions after treatment was significantly lower than lesional skin before treatment (P = 0.023). In psoriatic skin lesions of all studied patients IL-18 expression was significantly correlated with disease duration (r = 0.40 and P = 0.01) and clinical severity of psoriasis (r = 0.72 and P = 0.001). CONCLUSIONS: Increased IL-18 expression in keratinocytes from psoriatic lesions of our patients and its correlation with disease duration and severity supported the concept which views psoriasis as a T-cell-mediated autoimmune disease. This could establish therapeutic and preventive approaches for psoriasis that ultimately lead to improved outcomes for patients.,2010 Dec 29,"['Mohamed Attia, Hanaa Rasmy', 'Mikhael, Nancy', 'Ismail, Somaia']",Arch Med Sci,,,True
ffe718db1820f27bf274e3fc519ab78e450de288,PMC,Replication enhancer elements within the open reading frame of tick-borne encephalitis virus and their evolution within the Flavivirus genus,http://dx.doi.org/10.1093/nar/gkr237,PMC3303483,21622960,CC BY-NC,"We provide experimental evidence of a replication enhancer element (REE) within the capsid gene of tick-borne encephalitis virus (TBEV, genus Flavivirus). Thermodynamic and phylogenetic analyses predicted that the REE folds as a long stable stem–loop (designated SL6), conserved among all tick-borne flaviviruses (TBFV). Homologous sequences and potential base pairing were found in the corresponding regions of mosquito-borne flaviviruses, but not in more genetically distant flaviviruses. To investigate the role of SL6, nucleotide substitutions were introduced which changed a conserved hexanucleotide motif, the conformation of the terminal loop and the base-paired dsRNA stacking. Substitutions were made within a TBEV reverse genetic system and recovered mutants were compared for plaque morphology, single-step replication kinetics and cytopathic effect. The greatest phenotypic changes were observed in mutants with a destabilized stem. Point mutations in the conserved hexanucleotide motif of the terminal loop caused moderate virus attenuation. However, all mutants eventually reached the titre of wild-type virus late post-infection. Thus, although not essential for growth in tissue culture, the SL6 REE acts to up-regulate virus replication. We hypothesize that this modulatory role may be important for TBEV survival in nature, where the virus circulates by non-viraemic transmission between infected and non-infected ticks, during co-feeding on local rodents.",2011 Sep 27,"['Tuplin, A.', 'Evans, D. J.', 'Buckley, A.', 'Jones, I. M.', 'Gould, E. A.', 'Gritsun, T. S.']",Nucleic Acids Res,,,True
6c33cfdabc257f58702ac41cceeab41d02b2bb69,PMC,Replication enhancer elements within the open reading frame of tick-borne encephalitis virus and their evolution within the Flavivirus genus,http://dx.doi.org/10.1093/nar/gkr237,PMC3303483,21622960,CC BY-NC,"We provide experimental evidence of a replication enhancer element (REE) within the capsid gene of tick-borne encephalitis virus (TBEV, genus Flavivirus). Thermodynamic and phylogenetic analyses predicted that the REE folds as a long stable stem–loop (designated SL6), conserved among all tick-borne flaviviruses (TBFV). Homologous sequences and potential base pairing were found in the corresponding regions of mosquito-borne flaviviruses, but not in more genetically distant flaviviruses. To investigate the role of SL6, nucleotide substitutions were introduced which changed a conserved hexanucleotide motif, the conformation of the terminal loop and the base-paired dsRNA stacking. Substitutions were made within a TBEV reverse genetic system and recovered mutants were compared for plaque morphology, single-step replication kinetics and cytopathic effect. The greatest phenotypic changes were observed in mutants with a destabilized stem. Point mutations in the conserved hexanucleotide motif of the terminal loop caused moderate virus attenuation. However, all mutants eventually reached the titre of wild-type virus late post-infection. Thus, although not essential for growth in tissue culture, the SL6 REE acts to up-regulate virus replication. We hypothesize that this modulatory role may be important for TBEV survival in nature, where the virus circulates by non-viraemic transmission between infected and non-infected ticks, during co-feeding on local rodents.",2011 Sep 27,"['Tuplin, A.', 'Evans, D. J.', 'Buckley, A.', 'Jones, I. M.', 'Gould, E. A.', 'Gritsun, T. S.']",Nucleic Acids Res,,,False
3c919c2857ddedf0a444aa214761e16e4676d50b,PMC,Establishment of Epstein-Barr Virus Growth-transformed Lymphoblastoid Cell Lines,http://dx.doi.org/10.3791/3321,PMC3308597,22090023,CC BY-NC-ND,"Infection of B cells with Epstein-Barr virus (EBV) leads to proliferation and subsequent immortalization, resulting in establishment of lymphoblastoid cell lines (LCL) in vitro. Since LCL are latently infected with EBV, they provide a model system to investigate EBV latency and virus-driven B cell proliferation and tumorigenesis(1). LCL have been used to present antigens in a variety of immunologic assays(2, 3). In addition, LCL can be used to generate human monoclonal antibodies(4, 5) and provide a potentially unlimited source when access to primary biologic materials is limited(6, 7). A variety of methods have been described to generate LCL. Earlier methods have included the use of mitogens such as phytohemagglutinin, lipopolysaccharide(8), and pokeweed mitogen(9) to increase the efficiency of EBV-mediated immortalization. More recently, others have used immunosuppressive agents such as cyclosporin A to inhibit T cell-mediated killing of infected B cells(7, 10-12). The considerable length of time from EBV infection to establishment of cell lines drives the requirement for quicker and more reliable methods for EBV-driven B cell growth transformation. Using a combination of high titer EBV and an immunosuppressive agent, we are able to consistently infect, transform, and generate LCL from B cells in peripheral blood. This method uses a small amount of peripheral blood mononuclear cells that are infected in vitroclusters of cells can be demonstrated. The presence of CD23 with EBV in the presence of FK506, a T cell immunosuppressant. Traditionally, outgrowth of proliferating B cells is monitored by visualization of microscopic clusters of cells about a week after infection with EBV. Clumps of LCL can be seen by the naked eye after several weeks. We describe an assay to determine early if EBV-mediated growth transformation is successful even before microscopic clusters of cells can be demonstrated. The presence of CD23(hi)CD58(+) cells observed as early as three days post-infection indicates a successful outcome.",2011 Nov 8,"['Hui-Yuen, Joyce', 'McAllister, Shane', 'Koganti, Siva', 'Hill, Erik', 'Bhaduri-McIntosh, Sumita']",J Vis Exp,,,True
214d64d4237818509b17cb5ac82107116407b2e0,PMC,5′-Triphosphate-RNA-independent activation of RIG-I via RNA aptamer with enhanced antiviral activity,http://dx.doi.org/10.1093/nar/gkr1098,PMC3315321,22127865,CC BY-NC,"RIG-I is a cytosolic receptor for non-self RNA that mediates immune responses against viral infections through IFNα/β production. In an attempt to identify novel tools that modulate IFNα/β production, we used SELEX technology to screen RNA aptamers that specifically target RIG-I protein. Most of the selected RIG-I aptamers contained polyU motifs in the second half regions that played critical roles in the activation of RIG-I-mediated IFNβ production. Unlike other known ligands, RIG-I aptamer bound and activated RIG-I in a 5′-triphosphate-independent manner. The helicase and RD domain of RIG-I were used for aptamer binding, but intact RIG-I protein was required to exert aptamer-mediated signaling activation. Furthermore, replication of NDV, VSV and influenza virus in infected host cells was efficiently blocked by pre- or post-treatment with RIG-I aptamer. Based on these data, we propose that RIG-I aptamer has strong potential to be an antiviral agent that specifically boosts the RIG-I-dependent signaling cascade.",2012 Mar 29,"['Hwang, Sun-Young', 'Sun, Hwa-Young', 'Lee, Kwang-Hoon', 'Oh, Byung-Ha', 'Cha, Yu Jin', 'Kim, Byeang Hyean', 'Yoo, Joo-Yeon']",Nucleic Acids Res,,,True
fac2661e813598348dbb6d0370ed1818895c9f53,PMC,5′-Triphosphate-RNA-independent activation of RIG-I via RNA aptamer with enhanced antiviral activity,http://dx.doi.org/10.1093/nar/gkr1098,PMC3315321,22127865,CC BY-NC,"RIG-I is a cytosolic receptor for non-self RNA that mediates immune responses against viral infections through IFNα/β production. In an attempt to identify novel tools that modulate IFNα/β production, we used SELEX technology to screen RNA aptamers that specifically target RIG-I protein. Most of the selected RIG-I aptamers contained polyU motifs in the second half regions that played critical roles in the activation of RIG-I-mediated IFNβ production. Unlike other known ligands, RIG-I aptamer bound and activated RIG-I in a 5′-triphosphate-independent manner. The helicase and RD domain of RIG-I were used for aptamer binding, but intact RIG-I protein was required to exert aptamer-mediated signaling activation. Furthermore, replication of NDV, VSV and influenza virus in infected host cells was efficiently blocked by pre- or post-treatment with RIG-I aptamer. Based on these data, we propose that RIG-I aptamer has strong potential to be an antiviral agent that specifically boosts the RIG-I-dependent signaling cascade.",2012 Mar 29,"['Hwang, Sun-Young', 'Sun, Hwa-Young', 'Lee, Kwang-Hoon', 'Oh, Byung-Ha', 'Cha, Yu Jin', 'Kim, Byeang Hyean', 'Yoo, Joo-Yeon']",Nucleic Acids Res,,,True
1a6e69772e4e79d9106015988c0d6ed48dc25ceb,PMC,"Caspase cleavage of viral proteins, another way for viruses to make the best of apoptosis",http://dx.doi.org/10.1038/cddis.2012.18,PMC3317351,22402601,CC BY-NC-ND,"Viral infection constitutes an unwanted intrusion that needs to be eradicated by host cells. On one hand, one of the first protective barriers set up to prevent viral replication, spread or persistence involves the induction of apoptotic cell death that aims to limit the availability of the cellular components for viral amplification. On the other hand, while they completely depend on the host molecular machinery, viruses also need to evade the cellular responses that are meant to destroy them. The existence of numerous antiapoptotic products within the viral kingdom proves that apoptosis constitutes a major threat that should better be bypassed. Among the different strategies developed to deal with apoptosis, one is based on what viruses do best: backfiring the cell on itself. Several unrelated viruses have been described to take advantage of apoptosis induction by expressing proteins targeted by caspases, the key effectors of apoptotic cell death. Caspase cleavage of these proteins results in various consequences, from logical apoptosis inhibition to more surprising enhancement or attenuation of viral replication. The present review aims at discussing the characterization and relevance of this post-translational modification that adds a new complexity in the already intricate host–apoptosis–virus triangle.",2012 Mar 8,"['Richard, A', 'Tulasne, D']",Cell Death Dis,,,True
ff368c9be888417304869b18575ea6521dcc95b6,PMC,Echovirus 7 Entry into Polarized Intestinal Epithelial Cells Requires Clathrin and Rab7,http://dx.doi.org/10.1128/mBio.00304-11,PMC3324788,22496312,CC BY-NC-SA,"Enteroviruses invade the host by crossing the intestinal mucosa, which is lined by polarized epithelium. A number of enteroviruses, including echoviruses (EV) and group B coxsackieviruses (CVB), initiate infection by attaching to decay-accelerating factor (DAF), a molecule that is highly expressed on the apical surface of polarized epithelial cells. We previously observed that entry of DAF-binding CVB3 into polarized intestinal epithelial cells occurs by an unusual endocytic mechanism that requires caveolin but does not involve clathrin or dynamin. Here we examined the entry of a DAF-binding echovirus, EV7. We found that drugs, small interfering RNAs (siRNAs), and dominant negative mutants that target factors required for clathrin-mediated endocytosis, including clathrin and dynamin, inhibited both EV7 infection and internalization of virions from the cell surface. Once virus had entered the cell, it colocalized with markers of early endosomes (EEA1) and then late endosomes (LAMP-2). Inhibition of endosomal maturation—with siRNAs or dominant negative mutants targeting Rab5 and Rab7—inhibited infection and prevented release of viral RNA into the cell. These results indicate that EV7 is internalized by clathrin-mediated endocytosis and then moves to early and late endosomes before releasing its RNA. Trafficking through endosomes is known to be important for viruses that depend on low pH or endosomal cathepsin proteases to complete the entry process. However, we found that EV7 infection required neither low pH nor cathepsins.",2012 Apr 10,"['Kim, Chonsaeng', 'Bergelson, Jeffrey M.']",mBio,,,True
da5f78374b6b0b58d01188a2029fe9d74336e473,PMC,Baculovirus-based Vaccine Displaying Respiratory Syncytial Virus Glycoprotein Induces Protective Immunity against RSV Infection without Vaccine-Enhanced Disease,http://dx.doi.org/10.4110/in.2012.12.1.8,PMC3329602,22536165,CC BY-NC,"BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract diseases in infancy and early childhood. Despite its importance as a pathogen, there is no licensed vaccine against RSV yet. The attachment glycoprotein (G) of RSV is a potentially important target for protective antiviral immune responses. Recombinant baculovirus has been recently emerged as a new vaccine vector, since it has intrinsic immunostimulatory properties and good bio-safety profile. METHODS: We have constructed a recombinant baculovirus-based RSV vaccine, Bac-RSV/G, displaying G glycoprotein, and evaluated immunogenicity and protective efficacy by intranasal immunization of BALB/c mice with Bac-RSV/G. RESULTS: Bac-RSV/G efficiently provides protective immunity against RSV challenge. Strong serum IgG and mucosal IgA responses were induced by intranasal immunization with Bac-RSV/G. In addition to humoral immunity, G-specific Th17- as well as Th1-type T-cell responses were detected in the lungs of Bac-RSV/G-immune mice upon RSV challenge. Neither lung eosinophilia nor vaccine-induced weight loss was observed upon Bac-RSV/G immunization and subsequent RSV infection. CONCLUSION: Our data demonstrate that intranasal administration of baculovirus-based Bac-RSV/G vaccine is efficient for the induction of protection against RSV and represents a promising prophylactic vaccination regimen.",2012 Feb 29,"['Kim, Sol', 'Chang, Jun']",Immune Netw,,,True
043aa68f2c784899f71225e8eb233150760a6a54,PMC,Distribution and Risk Factors of 2009 Pandemic Influenza A (H1N1) in Mainland China,http://dx.doi.org/10.1093/aje/kwr411,PMC3339311,22491083,CC BY-NC,"Data from all reported cases of 2009 pandemic influenza A (H1N1) were obtained from the China Information System for Disease Control and Prevention. The spatiotemporal distribution patterns of cases were characterized through spatial analysis. The impact of travel-related risk factors on invasion of the disease was analyzed using survival analysis, and climatic factors related to local transmission were identified using multilevel Poisson regression, both at the county level. The results showed that the epidemic spanned a large geographic area, with the most affected areas being in western China. Significant differences in incidence were found among age groups, with incidences peaking in school-age children. Overall, the epidemic spread from southeast to northwest. Proximity to airports and being intersected by national highways or freeways but not railways were variables associated with the presence of the disease in a county. Lower temperature and lower relative humidity were the climatic factors facilitating local transmission after correction for the effects of school summer vacation and public holidays, as well as population density and the density of medical facilities. These findings indicate that interventions focused on domestic travel, population density, and climatic factors could play a role in mitigating the public health impact of future influenza pandemics.",2012 May 1,"['Fang, Li-Qun', 'Wang, Li-Ping', 'de Vlas, Sake J.', 'Liang, Song', 'Tong, Shi-Lu', 'Li, Yan-Li', 'Li, Ya-Pin', 'Qian, Quan', 'Yang, Hong', 'Zhou, Mai-Geng', 'Wang, Xiao-Feng', 'Richardus, Jan Hendrik', 'Ma, Jia-Qi', 'Cao, Wu-Chun']",Am J Epidemiol,,,True
3df5b3cb18ef7be1f94bb7a112690801983aed93,PMC,Distribution and Risk Factors of 2009 Pandemic Influenza A (H1N1) in Mainland China,http://dx.doi.org/10.1093/aje/kwr411,PMC3339311,22491083,CC BY-NC,"Data from all reported cases of 2009 pandemic influenza A (H1N1) were obtained from the China Information System for Disease Control and Prevention. The spatiotemporal distribution patterns of cases were characterized through spatial analysis. The impact of travel-related risk factors on invasion of the disease was analyzed using survival analysis, and climatic factors related to local transmission were identified using multilevel Poisson regression, both at the county level. The results showed that the epidemic spanned a large geographic area, with the most affected areas being in western China. Significant differences in incidence were found among age groups, with incidences peaking in school-age children. Overall, the epidemic spread from southeast to northwest. Proximity to airports and being intersected by national highways or freeways but not railways were variables associated with the presence of the disease in a county. Lower temperature and lower relative humidity were the climatic factors facilitating local transmission after correction for the effects of school summer vacation and public holidays, as well as population density and the density of medical facilities. These findings indicate that interventions focused on domestic travel, population density, and climatic factors could play a role in mitigating the public health impact of future influenza pandemics.",2012 May 1,"['Fang, Li-Qun', 'Wang, Li-Ping', 'de Vlas, Sake J.', 'Liang, Song', 'Tong, Shi-Lu', 'Li, Yan-Li', 'Li, Ya-Pin', 'Qian, Quan', 'Yang, Hong', 'Zhou, Mai-Geng', 'Wang, Xiao-Feng', 'Richardus, Jan Hendrik', 'Ma, Jia-Qi', 'Cao, Wu-Chun']",Am J Epidemiol,,,False
5157ee00e0ee6c807ca321c405baf2d8b9bd8a4f,PMC,CD8(+) T Cells in Leishmania Infections: Friends or Foes?,http://dx.doi.org/10.3389/fimmu.2012.00005,PMC3342007,22566891,CC BY-NC,"Host protection against several intracellular pathogens requires the induction of CD8(+) T cell responses. CD8(+) T cells are potent effector cells that can produce high amounts of pro-inflammatory cytokines and kill infected target cells efficiently. However, a protective role for CD8(+) T cells during Leishmania infections is still controversial and largely depends on the infection model. In this review, we discuss the role of CD8(+) T cells during various types of Leishmania infections, following vaccination, and as potential immunotherapeutic targets.",2012 Jan 24,"['Stäger, Simona', 'Rafati, Sima']",Front Immunol,,,True
0b627ea5840e5e48709565840313984dc900af8d,PMC,Macroevolutionary Immunology: A Role for Immunity in the Diversification of Animal life,http://dx.doi.org/10.3389/fimmu.2012.00025,PMC3342036,22566909,CC BY-NC,"An emerging picture of the nature of immune systems across animal phyla reveals both conservatism of some features and the appearance among and within phyla of novel, lineage-specific defense solutions. The latter collectively represent a major and underappreciated form of animal diversity. Factors influencing this macroevolutionary (above the species level) pattern of novelty are considered and include adoption of different life styles, life histories, and body plans; a general advantage of being distinctive with respect to immune defenses; and the responses required to cope with parasites, many of which afflict hosts in a lineage-specific manner. This large-scale pattern of novelty implies that immunological phenomena can affect microevolutionary processes (at the population level within species) that can eventually lead to macroevolutionary events such as speciation, radiations, or extinctions. Immunologically based phenomena play a role in favoring intraspecific diversification, specialization and host specificity of parasites, and mechanisms are discussed whereby this could lead to parasite speciation. Host switching – the acquisition of new host species by parasites – is a major mechanism that drives parasite diversity and is frequently involved in disease emergence. It is also one that can be favored by reductions in immune competence of new hosts. Mechanisms involving immune phenomena favoring intraspecific diversification and speciation of host species are also discussed. A macroevolutionary perspective on immunology is invaluable in today’s world, including the need to study a broader range of species with distinctive immune systems. Many of these species are faced with extinction, another macroevolutionary process influenced by immune phenomena.",2012 Mar 12,"Loker, Eric S.",Front Immunol,,,True
34fca1fbc149711e5617126584d1e26f06e94de9,PMC,Bats host major mammalian paramyxoviruses,http://dx.doi.org/10.1038/ncomms1796,PMC3343228,22531181,CC BY-NC-ND,"The large virus family Paramyxoviridae includes some of the most significant human and livestock viruses, such as measles-, distemper-, mumps-, parainfluenza-, Newcastle disease-, respiratory syncytial virus and metapneumoviruses. Here we identify an estimated 66 new paramyxoviruses in a worldwide sample of 119 bat and rodent species (9,278 individuals). Major discoveries include evidence of an origin of Hendra- and Nipah virus in Africa, identification of a bat virus conspecific with the human mumps virus, detection of close relatives of respiratory syncytial virus, mouse pneumonia- and canine distemper virus in bats, as well as direct evidence of Sendai virus in rodents. Phylogenetic reconstruction of host associations suggests a predominance of host switches from bats to other mammals and birds. Hypothesis tests in a maximum likelihood framework permit the phylogenetic placement of bats as tentative hosts at ancestral nodes to both the major Paramyxoviridae subfamilies (Paramyxovirinae and Pneumovirinae). Future attempts to predict the emergence of novel paramyxoviruses in humans and livestock will have to rely fundamentally on these data.",2012 Apr 24,"['Drexler, Jan Felix', 'Corman, Victor Max', 'Müller, Marcel Alexander', 'Maganga, Gael Darren', 'Vallo, Peter', 'Binger, Tabea', 'Gloza-Rausch, Florian', 'Rasche, Andrea', 'Yordanov, Stoian', 'Seebens, Antje', 'Oppong, Samuel', 'Sarkodie, Yaw Adu', 'Pongombo, Célestin', 'Lukashev, Alexander N.', 'Schmidt-Chanasit, Jonas', 'Stöcker, Andreas', 'Carneiro, Aroldo José Borges', 'Erbar, Stephanie', 'Maisner, Andrea', 'Fronhoffs, Florian', 'Buettner, Reinhard', 'Kalko, Elisabeth K.V.', 'Kruppa, Thomas', 'Franke, Carlos Roberto', 'Kallies, René', 'Yandoko, Emmanuel R.N.', 'Herrler, Georg', 'Reusken, Chantal', 'Hassanin, Alexandre', 'Krüger, Detlev H.', 'Matthee, Sonja', 'Ulrich, Rainer G.', 'Leroy, Eric M.', 'Drosten, Christian']",Nat Commun,,,True
3290019883fad88c1c40279e2783a739dc7363fa,PMC,Bats host major mammalian paramyxoviruses,http://dx.doi.org/10.1038/ncomms1796,PMC3343228,22531181,CC BY-NC-ND,"The large virus family Paramyxoviridae includes some of the most significant human and livestock viruses, such as measles-, distemper-, mumps-, parainfluenza-, Newcastle disease-, respiratory syncytial virus and metapneumoviruses. Here we identify an estimated 66 new paramyxoviruses in a worldwide sample of 119 bat and rodent species (9,278 individuals). Major discoveries include evidence of an origin of Hendra- and Nipah virus in Africa, identification of a bat virus conspecific with the human mumps virus, detection of close relatives of respiratory syncytial virus, mouse pneumonia- and canine distemper virus in bats, as well as direct evidence of Sendai virus in rodents. Phylogenetic reconstruction of host associations suggests a predominance of host switches from bats to other mammals and birds. Hypothesis tests in a maximum likelihood framework permit the phylogenetic placement of bats as tentative hosts at ancestral nodes to both the major Paramyxoviridae subfamilies (Paramyxovirinae and Pneumovirinae). Future attempts to predict the emergence of novel paramyxoviruses in humans and livestock will have to rely fundamentally on these data.",2012 Apr 24,"['Drexler, Jan Felix', 'Corman, Victor Max', 'Müller, Marcel Alexander', 'Maganga, Gael Darren', 'Vallo, Peter', 'Binger, Tabea', 'Gloza-Rausch, Florian', 'Rasche, Andrea', 'Yordanov, Stoian', 'Seebens, Antje', 'Oppong, Samuel', 'Sarkodie, Yaw Adu', 'Pongombo, Célestin', 'Lukashev, Alexander N.', 'Schmidt-Chanasit, Jonas', 'Stöcker, Andreas', 'Carneiro, Aroldo José Borges', 'Erbar, Stephanie', 'Maisner, Andrea', 'Fronhoffs, Florian', 'Buettner, Reinhard', 'Kalko, Elisabeth K.V.', 'Kruppa, Thomas', 'Franke, Carlos Roberto', 'Kallies, René', 'Yandoko, Emmanuel R.N.', 'Herrler, Georg', 'Reusken, Chantal', 'Hassanin, Alexandre', 'Krüger, Detlev H.', 'Matthee, Sonja', 'Ulrich, Rainer G.', 'Leroy, Eric M.', 'Drosten, Christian']",Nat Commun,,,True
0f6091029a2cc8ddd6a5c6ee18de7478b73daab2,PMC,Genome Stability of Pandemic Influenza A (H1N1) 2009 Based on Analysis of Hemagglutinin and Neuraminidase Genes,http://dx.doi.org/10.2174/1874357901206010059,PMC3349948,22582106,CC BY-NC,"Influenza A virus (H1N1), which arose in 2009, constituted the fourth pandemic after the cases of 1918, 1957, and 1968. This new variant was formed by a triple reassortment, with genomic segments from swine, avian, and human influenza origins. The objective of this study was to analyze sequences of hemagglutinin (n=2038) and neuraminidase (n=1273) genes, in order to assess the extent of diversity among circulating 2009-2010 strains, estimate if these genes evolved through positive, negative, or neutral selection models of evolution during the pandemic phase, and analyze the worldwide percentage of detection of important amino acid mutations that could enhance the viral performance, such as transmissibility or resistance to drugs. A continuous surveillance by public health authorities will be critical to monitor the appearance of new influenza variants, especially in animal reservoirs such as swine and birds, in order to prevent the potential animal-human transmission of viruses with pandemic potential.",2012 Apr 26,"Espínola, Emilio E",Open Virol J,,,True
400b727ebfb163cf31705a950423bee6710eb058,PMC,Genome Stability of Pandemic Influenza A (H1N1) 2009 Based on Analysis of Hemagglutinin and Neuraminidase Genes,http://dx.doi.org/10.2174/1874357901206010059,PMC3349948,22582106,CC BY-NC,"Influenza A virus (H1N1), which arose in 2009, constituted the fourth pandemic after the cases of 1918, 1957, and 1968. This new variant was formed by a triple reassortment, with genomic segments from swine, avian, and human influenza origins. The objective of this study was to analyze sequences of hemagglutinin (n=2038) and neuraminidase (n=1273) genes, in order to assess the extent of diversity among circulating 2009-2010 strains, estimate if these genes evolved through positive, negative, or neutral selection models of evolution during the pandemic phase, and analyze the worldwide percentage of detection of important amino acid mutations that could enhance the viral performance, such as transmissibility or resistance to drugs. A continuous surveillance by public health authorities will be critical to monitor the appearance of new influenza variants, especially in animal reservoirs such as swine and birds, in order to prevent the potential animal-human transmission of viruses with pandemic potential.",2012 Apr 26,"Espínola, Emilio E",Open Virol J,,,False
1a39379895d1e136f64c7b79ef2204de094dfa75,PMC,Pilot Evaluation of RT-PCR/Electrospray Ionization Mass Spectrometry (PLEX-ID/Flu assay) on Influenza-Positive Specimens,http://dx.doi.org/10.2174/1874357901206010064,PMC3355350,22611461,CC BY-NC,"The PLEX-ID/Flu assay has been recently developed to enable the detection and typing of influenza viruses based on the RT-PCR/electrospray ionization mass spectrometry technology. This novel assay was evaluated for typing performance on 201 positive influenza A or B nasopharyngeal swab specimens (NPS) detected by real-time RT-PCR during the 2010-2011 season. The PLEX-ID/Flu assay detected and characterized 91.3% and 95.3% of all influenza A and B samples, respectively. All non-typeable influenza A and B specimens by the assay showed low viral loads with threshold cycle values ≥ 33. Taken together, and although our results need to be confirmed by further prospective studies, the PLEX-ID/Flu assay detected positively and gave a typing result for 93% of all NPS detected positively by real-time RT-PCR, thus suggesting a potential role for influenza virus surveillance among other techniques.",2012 May 9,"['Cordey, Samuel', 'Thomas, Yves', 'Suter, Patricia', 'Kaiser, Laurent']",Open Virol J,,,True
1f541a086ac9bc30df8ee2060f958691fb4a0667,PMC,"Association of TNF-α –308G/A, SP-B 1580 C/T, IL-13 –1055 C/T gene polymorphisms and latent adenoviral infection with chronic obstructive pulmonary disease in an Egyptian population",http://dx.doi.org/10.5114/aoms.2012.28556,PMC3361041,22662002,CC BY-NC-ND,"INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and death. The most common cause of COPD is smoking. There is evidence suggesting that genetic factors influence COPD susceptibility and variants in several candidate genes have been significantly associated with COPD. In this study, we aimed to investigate the possible association of the TNF-α –308, SPB+1580, IL-13 –1055 gene polymorphisms and latent adenovirus C infection with COPD in an Egyptian population. MATERIAL AND METHODS: Our study included 115 subjects (75 smokers with COPD, 25 resistant smokers and 15 non-smokers) who were subjected to spirometric measurements, identification of adenovirus C and genotyping of TNF-α –308G/A, SP-B+1580 C/T and IL-13 –1055 C/T polymorphisms by real-time PCR. RESULTS: The adenovirus C gene was identified in all subjects. The distribution of TNF-α genotypes showed no significant differences between different groups. However, homozygous A genotype was associated with a significant decrease in FEV(1), FEV(1)/FVC and FEF25/75% of predicted in COPD (p < 0.05). As regards SP-B genotypes, resistant smokers had a significantly higher homozygous T genotype frequency compared to COPD and non smokers (p = 0.005). Interleukin 13 genotypes showed no significant difference between different groups. There was a significant decrease in FEF25/75% of predicted in T allele carriers in COPD patients (p = 0.001). CONCLUSIONS: The COPD is a disease caused by the interaction of combined genes and environmental influences, in the presence of smoking and latent adenovirus C infection, TNF-α –308A, SPB +1580 T and IL-13 –1055 T polymorphisms predispose to the development of COPD.",2012 May 9,"['Ezzeldin, Nada', 'Shalaby, Alaa', 'Saad-Hussein, Amal', 'Ezzeldin, Howayda', 'El Lebedy, Dalia', 'Farouk, Hebatallah', 'Kandil, Dina M.']",Arch Med Sci,,,True
9cd8c3706551ab124d7035449350556c72297e2e,PMC,Binding of the 5′-untranslated region of coronavirus RNA to zinc finger CCHC-type and RNA-binding motif 1 enhances viral replication and transcription,http://dx.doi.org/10.1093/nar/gks165,PMC3367200,22362731,CC BY-NC,"Coronaviruses RNA synthesis occurs in the cytoplasm and is regulated by host cell proteins. In a screen based on a yeast three-hybrid system using the 5′-untranslated region (5′-UTR) of SARS coronavirus (SARS-CoV) RNA as bait against a human cDNA library derived from HeLa cells, we found a positive candidate cellular protein, zinc finger CCHC-type and RNA-binding motif 1 (MADP1), to be able to interact with this region of the SARS-CoV genome. This interaction was subsequently confirmed in coronavirus infectious bronchitis virus (IBV). The specificity of the interaction between MADP1 and the 5′-UTR of IBV was investigated and confirmed by using an RNA pull-down assay. The RNA-binding domain was mapped to the N-terminal region of MADP1 and the protein binding sequence to stem–loop I of IBV 5′-UTR. MADP1 was found to be translocated to the cytoplasm and partially co-localized with the viral replicase/transcriptase complexes (RTCs) in IBV-infected cells, deviating from its usual nuclear localization in a normal cell using indirect immunofluorescence. Using small interfering RNA (siRNA) against MADP1, defective viral RNA synthesis was observed in the knockdown cells, therefore indicating the importance of the protein in coronaviral RNA synthesis.",2012 Jun 22,"['Tan, Yong Wah', 'Hong, Wanjin', 'Liu, Ding Xiang']",Nucleic Acids Res,,,True
74bc0b72bd1e1984f0428c90223d5f9cceda5f22,PMC,"An Insight into the Diverse Roles of Surfactant Proteins, SP-A and SP-D in Innate and Adaptive Immunity",http://dx.doi.org/10.3389/fimmu.2012.00131,PMC3369187,22701116,CC BY-NC,"Surfactant proteins SP-A and SP-D are hydrophilic, collagen-containing calcium-dependent lectins, which appear to have a range of innate immune functions at pulmonary as well as extrapulmonary sites. These proteins bind to target ligands on pathogens, allergens, and apoptotic cells, via C-terminal homotrimeric carbohydrate recognition domains, while the collagen region brings about the effector functions via its interaction with cell surface receptors. SP-A and SP-D deal with various pathogens, using a range of innate immune mechanisms such as agglutination/aggregation, enhancement of phagocytosis, and killing mechanisms by phagocytic cells and direct growth inhibition. SP-A and SP-D have also been shown to be involved in the control of pulmonary inflammation including allergy and asthma. Emerging evidence suggest that SP-A and SP-D are capable of linking innate immunity with adaptive immunity that includes modulation of dendritic cell function and helper T cell polarization. This review enumerates immunological properties of SP-A and SP-D inside and outside lungs and discusses their importance in human health and disease.",2012 Jun 7,"['Nayak, Annapurna', 'Dodagatta-Marri, Eswari', 'Tsolaki, Anthony George', 'Kishore, Uday']",Front Immunol,,,True
049364026266fb6b0b8d8a626844823a3036e5b0,PMC,Animal viral diseases and global change: bluetongue and West Nile fever as paradigms,http://dx.doi.org/10.3389/fgene.2012.00105,PMC3374460,22707955,CC BY-NC,"Environmental changes have an undoubted influence on the appearance, distribution, and evolution of infectious diseases, and notably on those transmitted by vectors. Global change refers to environmental changes arising from human activities affecting the fundamental mechanisms operating in the biosphere. This paper discusses the changes observed in recent times with regard to some important arboviral (arthropod-borne viral) diseases of animals, and the role global change could have played in these variations. Two of the most important arboviral diseases of animals, bluetongue (BT) and West Nile fever/encephalitis (WNF), have been selected as models. In both cases, in the last 15 years an important leap forward has been observed, which has lead to considering them emerging diseases in different parts of the world. BT, affecting domestic ruminants, has recently afflicted livestock in Europe in an unprecedented epizootic, causing enormous economic losses. WNF affects wildlife (birds), domestic animals (equines), and humans, thus, beyond the economic consequences of its occurrence, as a zoonotic disease, it poses an important public health threat. West Nile virus (WNV) has expanded in the last 12 years worldwide, and particularly in the Americas, where it first occurred in 1999, extending throughout the Americas relentlessly since then, causing a severe epidemic of disastrous consequences for public health, wildlife, and livestock. In Europe, WNV is known long time ago, but it is since the last years of the twentieth century that its incidence has risen substantially. Circumstances such as global warming, changes in land use and water management, increase in travel, trade of animals, and others, can have an important influence in the observed changes in both diseases. The following question is raised: What is the contribution of global changes to the current increase of these diseases in the world?",2012 Jun 13,"Jiménez-Clavero, Miguel Á",Front Genet,,,True
16c8b4fe2b6ae40077de377027c4fdf6a27a0744,PMC,Two Series of Familial Cases With Unclassified Interstitial Pneumonia With Fibrosis,http://dx.doi.org/10.4168/aair.2012.4.4.240,PMC3378931,22754718,CC BY-NC,"Several children presenting with mild symptoms of respiratory tract infection were diagnosed with unclassified interstitial pneumonia with fibrosis. Their clinical and radiological findings were similar to those of acute interstitial pneumonia, but there were some differences in the pathological findings. Unclassified interstitial pneumonia with fibrosis is characterized by histological findings of centrilobular distribution of alveolar damage and bronchiolar destruction with bronchiolar obliteration. This report describes two different series of familial cases of unclassified interstitial pneumonia with fibrosis, which developed almost simultaneously in the spring. Some of the individual cases showed rapidly progressive respiratory failure of unknown cause, with comparable clinical courses and similar radiological and pathological features, including lung fibrosis. Each family member was affected almost simultaneously in the spring, different kinds of viruses were detected in two patients, and all members were negative for bacterial infection, environmental and occupational agents, drugs, and radiation. These findings implicate a viral infection and/or processes related to a viral infection, such as an exaggerated or altered immune response, or an unknown inhaled environmental agent in the pathogenesis of unclassified interstitial pneumonia with fibrosis.",2012 Jul 9,"['Lee, Eun', 'Seo, Ju-Hee', 'Kim, Hyoung-Young', 'Yu, Jinho', 'Song, Jin Woo', 'Park, Young Soo', 'Jang, Se-Jin', 'Do, Kyung-Hyun', 'Kwon, Jiwon', 'Park, Sung-woo', 'Park, Jeong-hwan', 'Hong, Soo-Jong']",Allergy Asthma Immunol Res,,,True
2105c805d6a0a560348c1bb6bf620685944ba9dc,PMC,Lipid Rafts and Alzheimer’s Disease: Protein-Lipid Interactions and Perturbation of Signaling,http://dx.doi.org/10.3389/fphys.2012.00189,PMC3381238,22737128,CC BY-NC,"Lipid rafts are membrane domains, more ordered than the bulk membrane and enriched in cholesterol and sphingolipids. They represent a platform for protein-lipid and protein–protein interactions and for cellular signaling events. In addition to their normal functions, including membrane trafficking, ligand binding (including viruses), axonal development and maintenance of synaptic integrity, rafts have also been implicated in the pathogenesis of several neurodegenerative diseases including Alzheimer’s disease (AD). Lipid rafts promote interaction of the amyloid precursor protein (APP) with the secretase (BACE-1) responsible for generation of the amyloid β peptide, Aβ. Rafts also regulate cholinergic signaling as well as acetylcholinesterase and Aβ interaction. In addition, such major lipid raft components as cholesterol and GM1 ganglioside have been directly implicated in pathogenesis of the disease. Perturbation of lipid raft integrity can also affect various signaling pathways leading to cellular death and AD. In this review, we discuss modulation of APP cleavage by lipid rafts and their components, while also looking at more recent findings on the role of lipid rafts in signaling events.",2012 Jun 22,"['Hicks, David A.', 'Nalivaeva, Natalia N.', 'Turner, Anthony J.']",Front Physiol,,,True
808f6be54af8e7c20446dc1ebdeeb68af2c28fba,PMC,A Case of Acute Disseminated Encephalomyelitis Associated with Hepatitis C Virus Infection,http://dx.doi.org/10.3349/ymj.2012.53.4.856,PMC3381478,22665357,CC BY-NC,"Acute disseminated encephalomyelitis (ADEM) is a monophasic autoimmune demyelinating disease of the central nervous system, which typically follows acute viral or bacterial infection or vaccination. We report a case of ADEM associated with hepatitis C virus (HCV) infection with positive serum and cerebrospinal fluid (CSF) anti-HCV antibody. After steroid treatment, neurologic symptoms were improved. Virus triggers autoimmunity or direct viral invasion plays a part in the genesis of ADEM. This is the first reported case of ADEM with anti-HCV antibody in the CSF.",2012 Jul 1,"['Sim, Jae Eun', 'Lee, Jun-Bum', 'Cho, Yu Na', 'Suh, Sang Hyun', 'Kim, Ja Kyung', 'Lee, Kyung-Yul']",Yonsei Med J,,,True
05df6a79e61e69b9113ffa6a667c3fb9b2680e70,PMC,TLR9 agonists induced cell death in Burkitt's lymphoma cells is variable and influenced by TLR9 polymorphism,http://dx.doi.org/10.1038/cddis.2012.60,PMC3388232,22717578,CC BY-NC-ND,"Toll-like receptor 9 (TLR9) triggering is a promising novel strategy to combat cancer as it induces innate and adaptive immunity responses. B-cell lymphoma is unique in this context as tumor cells express TLR9 and may harbor latent Epstein-Barr virus (EBV), a gamma-herpesvirus with remarkable oncogenic potential when latent. Latent EBV may be promoted by TLR9 triggering via suppression of lytic EBV. Here, we elaborated an initial assessment of the impact of TLR9 triggering on EBV-positive and EBV-negative B-cell lymphoma using Burkitt's lymphoma (BL) cell lines as an in vitro model. We show that, independent of the presence of EBV, the TLR9 ligand oligodeoxynucleotide (ODN) CpG-2006 may or may not induce caspase-dependent cell death in BL cells. Moreover, ODN CpG-2006-induced cell death responses of BL cells were associated with TLR9 single-nucleotide polymorphisms (SNPs) rs5743836 or rs352140, which we detected in primary BL tumors and in peripheral blood from healthy individuals at similar frequencies. Thus, our findings suggest that the effect of TLR9 agonists on BL cells should be tested in vitro before installment of therapy and TLR9 SNPs in BL patients should be determined as potential biological markers for the therapeutic response to treatment targeting innate immunity.",2012 Jun 21,"['Noack, J', 'Jordi, M', 'Zauner, L', 'Alessi, D', 'Burch, A', 'Tinguely, M', 'Hersberger, M', 'Bernasconi, M', 'Nadal, D']",Cell Death Dis,,,True
9f9327703d4203ad1f26dfea48d1a0226e6dd5d4,PMC,Acute lung injury and acute respiratory distress syndrome: experimental and clinical investigations,http://dx.doi.org/10.3724/SP.J.1263.2011.00044,PMC3390060,22783284,CC BY-NC-SA,"Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) can be associated with various disorders. Recent investigation has involved clinical studies in collaboration with clinical investigators and pathologists on the pathogenetic mechanisms of ALI or ARDS caused by various disorders. This literature review includes a brief historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the long-term experimental studies and clinical investigations from our laboratory, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.",2011 Mar,"Chen, Hsing I",J Geriatr Cardiol,,,True
6979d40067c7917b6b92917ff8c3db8a440f5f4c,PMC,Deciphering Novel Host–Herpesvirus Interactions by Virion Proteomics,http://dx.doi.org/10.3389/fmicb.2012.00181,PMC3390586,22783234,CC BY-NC,"Over the years, a vast array of information concerning the interactions of viruses with their hosts has been collected. However, recent advances in proteomics and other system biology techniques suggest these interactions are far more complex than anticipated. One particularly interesting and novel aspect is the analysis of cellular proteins incorporated into mature virions. Though sometimes considered purification contaminants in the past, their repeated detection by different laboratories suggests that a number of these proteins are bona fide viral components, some of which likely contribute to the viral life cycles. The present mini review focuses on cellular proteins detected in herpesviruses. It highlights the common cellular functions of these proteins, their potential implications for host–pathogen interactions, discusses technical limitations, the need for complementing methods and probes potential future research avenues.",2012 May 28,"Lippé, Roger",Front Microbiol,,,True
e552060ddffa5574e514e54986f35acb95bcc4dc,PMC,VIGOR extended to annotate genomes for additional 12 different viruses,http://dx.doi.org/10.1093/nar/gks528,PMC3394299,22669909,CC BY-NC,"A gene prediction program, VIGOR (Viral Genome ORF Reader), was developed at J. Craig Venter Institute in 2010 and has been successfully performing gene calling in coronavirus, influenza, rhinovirus and rotavirus for projects at the Genome Sequencing Center for Infectious Diseases. VIGOR uses sequence similarity search against custom protein databases to identify protein coding regions, start and stop codons and other gene features. Ribonucleicacid editing and other features are accurately identified based on sequence similarity and signature residues. VIGOR produces four output files: a gene prediction file, a complementary DNA file, an alignment file, and a gene feature table file. The gene feature table can be used to create GenBank submission. VIGOR takes a single input: viral genomic sequences in FASTA format. VIGOR has been extended to predict genes for 12 viruses: measles virus, mumps virus, rubella virus, respiratory syncytial virus, alphavirus and Venezuelan equine encephalitis virus, norovirus, metapneumovirus, yellow fever virus, Japanese encephalitis virus, parainfluenza virus and Sendai virus. VIGOR accurately detects the complex gene features like ribonucleicacid editing, stop codon leakage and ribosomal shunting. Precisely identifying the mat_peptide cleavage for some viruses is a built-in feature of VIGOR. The gene predictions for these viruses have been evaluated by testing from 27 to 240 genomes from GenBank.",2012 Jul 4,"['Wang, Shiliang', 'Sundaram, Jaideep P.', 'Stockwell, Timothy B.']",Nucleic Acids Res,,,True
6ce22e4f892e54b0f6317315b113f3fd46ed7245,PMC,Analysis on the Pathogenesis of Symptomatic Pulmonary Embolism with Human Genomics,http://dx.doi.org/10.7150/ijms.4641,PMC3399218,22811612,CC BY-NC-ND,"BACKGROUND: In the present study, the whole human genome oligo microarray was employed to investigate the gene expression profile in symptomatic pulmonary embolism (PE). METHODS: Twenty patients with PE and 20 age and gender matched patients without PE as controls were enrolled into the present study in the same period. The diagnosis of PE was based on the clinical manifestations and findings on imaging examinations. Acute arterial and/or venous thrombosis was excluded in controls. The whole human genome oligo microarray was employed for detection. Statistical analysis was performed with t test following analysis of very small samples of repeated measurements and Gene Ontology (GO) analysis. RESULTS: Genomic data showed no damage to vascular endothelial cells in PE patients. Genomic data only found increased mRNA expression of a small amount of coagulation factors in PE patients. In the PE group, anticoagulant proteins, Fibrinolytic system and proteins related to platelet functions only played partial roles in the pathogenesis of PE. In addition, the mRNA expressions of a fraction of adhesion molecules were markedly up-regulated. Gene Ontology analysis showed the genes with down-regulated expressions mainly explain the compromised T cell immunity. Symptomatic VTE patients have compromised T cell immunity. CONCLUSION: The damage to vascular endothelial cells is not necessary in the pathogenesis of VTE, and only a fraction of factors involved in the shared coagulation cascade are activated. Genomic results may provide a new clue for clinical diagnosis, treatment and prevention of VTE.",2012 Jul 11,"['Wang, Hao', 'Duan, Qianglin', 'Wang, Lemin', 'Gong, Zhu', 'Liang, Aibin', 'Wang, Qiang', 'Song, Haoming', 'Yang, Fan', 'Song, Yanli']",Int J Med Sci,,,True
7e3f8778b0ccf9aa5fe2a4e0ee2740f01691bca5,PMC,Geographical Information Systems and Health: Current State and Future Directions,http://dx.doi.org/10.4258/hir.2012.18.2.88,PMC3402560,22844644,CC BY-NC,"This paper provides an introduction to Geographical Information Systems (GIS) and how they can be used. It reviews the current state of GIS use in health care before identifying the barriers to more pervasive use of GIS in health. Finally, it makes recommendations for the direction of health GIS research over the next decade and concludes with a call to action to health informatics researchers to stop ignoring a tool and methodology that has such immense potential for improving the health of our communities.",2012 Jun 30,"Shaw, Nicola T.",Healthc Inform Res,,,True
50641a70bd884557e33cd969cd77a0f724f4dda6,PMC,"Seasonal influenza vaccination knowledge, risk perception, health beliefs and vaccination behaviours of nurses",http://dx.doi.org/10.1017/S0950268811002214,PMC3405768,22093804,CC BY-NC-SA,"The relationship between knowledge, risk perceptions, health belief towards seasonal influenza and vaccination and the vaccination behaviours of nurses was explored. Qualified nurses attending continuing professional education courses at a large London university between 18 April and 18 October 2010 were surveyed (522/672; response rate 77·7%). Of these, 82·6% worked in hospitals; 37·0% reported receiving seasonal influenza vaccination in the previous season and 44·9% reported never being vaccinated during the last 5 years. All respondents were categorized using two-step cluster analyses into never, occasionally, and continuously vaccinated groups. Nurses vaccinated the season before had higher scores of knowledge and risk perception compared to the unvaccinated (P<0·001). Nurses never vaccinated had the lowest scores of knowledge and risk perception compared to other groups (P<0·001). Nurses' seasonal influenza vaccination behaviours are complex. Knowledge and risk perception predict uptake of vaccination in nurses.",2012 Sep 18,"['ZHANG, J.', 'WHILE, A. E.', 'NORMAN, I. J.']",Epidemiol Infect,,,True
d800e113c0f37fea4586a18115d07a7bbb3e5464,PMC,The ATF6 branch of unfolded protein response and apoptosis are activated to promote African swine fever virus infection,http://dx.doi.org/10.1038/cddis.2012.81,PMC3406580,22764100,CC BY-NC-ND,"African swine fever virus (ASFV) infection induces apoptosis in the infected cell; however, the consequences of this activation on virus replication have not been defined. In order to identify the role of apoptosis in ASFV infection, we analyzed caspase induction during the infection and the impact of caspase inhibition on viral production. Caspases 3, 9 and 12 were activated from 16 h post-infection, but not caspase 8. Indeed, caspase 3 activation during the early stages of the infection appeared to be crucial for efficient virus exit. In addition, the inhibition of membrane blebbing reduced the release of virus particles from the cell. ASFV uses the endoplasmic reticulum (ER) as a site of replication and this process can trigger ER stress and the unfolded protein response (UPR) of the host cell. In addition to caspase 12 activation, indicators of ER stress include the upregulation of the chaperones calnexin and calreticulin upon virus infection. Moreover, ASFV induces transcription factor 6 signaling pathway of the UPR, but not the protein kinase-like ER kinase or the inositol-requiring enzyme 1 pathways. Thus, the capacity of ASFV to regulate the UPR may prevent early apoptosis and ensure viral replication.",2012 Jul 5,"['Galindo, I', 'Hernáez, B', 'Muñoz-Moreno, R', 'Cuesta-Geijo, M A', 'Dalmau-Mena, I', 'Alonso, C']",Cell Death Dis,,,True
a497dea73b329a11331c9835fabff84a7e5eedcd,PMC,Symptomatic Venous Thromboembolism Is a Disease Related to Infection and Immune Dysfunction,http://dx.doi.org/10.7150/ijms.4453,PMC3410365,22859906,CC BY-NC-ND,"The characteristics of human genomics and cellular immune function between clinically symptomatic venous thromboembolism (VTE) and controls were systematically compared to explore the immunologic pathogenesis of VTE. Microarray assay showed the mRNA expressions of genes related to non-specific cellarer immune and cytokines were significantly down-regulated. Abnormal expressions of CD3+, CD4+, CD8+, NK marker CD16+56+, CD19 and aberrant CD4+/CD8+ ratio were detected in 54 among 56 patients. In PE patients, microarray assay revealed the imbalance in the expressions of genes related to the immune system. The expressions of genes related to non-specific immune cells and cytokines were markedly up-regulated and those associated with cellular immune were dramatically down-regulated. In VTE patients, cytological examination indicated the functions of NK cells were significantly compromised, and the antigen recognition and killing function of T cells markedly decreased. The consistence between genomic and cytological examination suggests the symptomatic VTE is closely associated with the infection and immune dysfunction.",2012 Jul 26,"['Duan, Qianglin', 'Gong, Zhu', 'Song, Haoming', 'Wang, Lemin', 'Yang, Fan', 'Lv, Wei', 'Song, Yanli']",Int J Med Sci,,,True
93f3546142cf477c77ef113ed4ff98a881a2c8c1,PMC,Practical pathology of aging mice,http://dx.doi.org/10.3402/pba.v1i0.7202,PMC3417704,22953032,CC BY-NC,"Old mice will have a subset of lesions as part of the progressive decline in organ function that defines aging. External and palpable lesions will be noted by the research, husbandry, or veterinary staff during testing, cage changing, or physical exams. While these readily observable lesions may cause alarm, not all cause undue distress or are life-threatening. In aging research, mice are maintained until near end of life that, depending on strain and genetic manipulation, can be upwards of 33 months. Aging research has unique welfare issues related to age-related decline, debilitation, fragility, and associated pain of chronic diseases. An effective aging research program includes the collaboration and education of the research, husbandry, and veterinary staff, and of the members of the institution animal care and use committee. This collaborative effort is critical to humanely maintaining older mice and preventing excessive censorship due to non-lethal diseases. Part of the educational process is becoming familiar with how old mice appear clinically, at necropsy and histopathologically. This baseline knowledge is important in making the determination of humane end points, defining health span, contributing causes of death and effects of interventions. The goal of this paper is to introduce investigators to age-associated diseases and lesion patterns in mice from clinical presentation to pathologic assessment. To do so, we present and illustrate the common clinical appearances, necropsy and histopathological lesions seen in subsets of the aging colonies maintained at the University of Washington.",2011 Jun 1,"['Pettan-Brewer, Christina', 'Treuting, Piper M.']",Pathobiol Aging Age Relat Dis,,,True
571e8706c0aff7482c60e60cad9d1334c917df12,PMC,"Identification, Characterization, and In Vitro Culture of Highly Divergent Arenaviruses from Boa Constrictors and Annulated Tree Boas: Candidate Etiological Agents for Snake Inclusion Body Disease",http://dx.doi.org/10.1128/mBio.00180-12,PMC3419519,22893382,CC BY-NC-SA,"Inclusion body disease (IBD) is an infectious fatal disease of snakes typified by behavioral abnormalities, wasting, and secondary infections. At a histopathological level, the disease is identified by the presence of large eosinophilic cytoplasmic inclusions in multiple tissues. To date, no virus or other pathogen has been definitively characterized or associated with the disease. Using a metagenomic approach to search for candidate etiologic agents in snakes with confirmed IBD, we identified and de novo assembled the complete genomic sequences of two viruses related to arenaviruses, and a third arenavirus-like sequence was discovered by screening an additional set of samples. A continuous boa constrictor cell line was established and used to propagate and isolate one of the viruses in culture. Viral nucleoprotein was localized and concentrated within large cytoplasmic inclusions in infected cells in culture and tissues from diseased snakes. In total, viral RNA was detected in 6/8 confirmed IBD cases and 0/18 controls. These viruses have a typical arenavirus genome organization but are highly divergent, belonging to a lineage separate from that of the Old and New World arenaviruses. Furthermore, these viruses encode envelope glycoproteins that are more similar to those of filoviruses than to those of other arenaviruses. These findings implicate these viruses as candidate etiologic agents of IBD. The presence of arenaviruses outside mammals reveals that these viruses infect an unexpectedly broad range of species and represent a new reservoir of potential human pathogens.",2012 Aug 14,"['Stenglein, Mark D.', 'Sanders, Chris', 'Kistler, Amy L.', 'Ruby, J. Graham', 'Franco, Jessica Y.', 'Reavill, Drury R.', 'Dunker, Freeland', 'DeRisi, Joseph L.']",mBio,,,True
0b3afc1d54b967632b252f7270d4504598aecfa2,PMC,"Identification, Characterization, and In Vitro Culture of Highly Divergent Arenaviruses from Boa Constrictors and Annulated Tree Boas: Candidate Etiological Agents for Snake Inclusion Body Disease",http://dx.doi.org/10.1128/mBio.00180-12,PMC3419519,22893382,CC BY-NC-SA,"Inclusion body disease (IBD) is an infectious fatal disease of snakes typified by behavioral abnormalities, wasting, and secondary infections. At a histopathological level, the disease is identified by the presence of large eosinophilic cytoplasmic inclusions in multiple tissues. To date, no virus or other pathogen has been definitively characterized or associated with the disease. Using a metagenomic approach to search for candidate etiologic agents in snakes with confirmed IBD, we identified and de novo assembled the complete genomic sequences of two viruses related to arenaviruses, and a third arenavirus-like sequence was discovered by screening an additional set of samples. A continuous boa constrictor cell line was established and used to propagate and isolate one of the viruses in culture. Viral nucleoprotein was localized and concentrated within large cytoplasmic inclusions in infected cells in culture and tissues from diseased snakes. In total, viral RNA was detected in 6/8 confirmed IBD cases and 0/18 controls. These viruses have a typical arenavirus genome organization but are highly divergent, belonging to a lineage separate from that of the Old and New World arenaviruses. Furthermore, these viruses encode envelope glycoproteins that are more similar to those of filoviruses than to those of other arenaviruses. These findings implicate these viruses as candidate etiologic agents of IBD. The presence of arenaviruses outside mammals reveals that these viruses infect an unexpectedly broad range of species and represent a new reservoir of potential human pathogens.",2012 Aug 14,"['Stenglein, Mark D.', 'Sanders, Chris', 'Kistler, Amy L.', 'Ruby, J. Graham', 'Franco, Jessica Y.', 'Reavill, Drury R.', 'Dunker, Freeland', 'DeRisi, Joseph L.']",mBio,,,False
da98df13c3bf55e28bc3e778d2b65d343ffd41dc,PMC,"Identification, Characterization, and In Vitro Culture of Highly Divergent Arenaviruses from Boa Constrictors and Annulated Tree Boas: Candidate Etiological Agents for Snake Inclusion Body Disease",http://dx.doi.org/10.1128/mBio.00180-12,PMC3419519,22893382,CC BY-NC-SA,"Inclusion body disease (IBD) is an infectious fatal disease of snakes typified by behavioral abnormalities, wasting, and secondary infections. At a histopathological level, the disease is identified by the presence of large eosinophilic cytoplasmic inclusions in multiple tissues. To date, no virus or other pathogen has been definitively characterized or associated with the disease. Using a metagenomic approach to search for candidate etiologic agents in snakes with confirmed IBD, we identified and de novo assembled the complete genomic sequences of two viruses related to arenaviruses, and a third arenavirus-like sequence was discovered by screening an additional set of samples. A continuous boa constrictor cell line was established and used to propagate and isolate one of the viruses in culture. Viral nucleoprotein was localized and concentrated within large cytoplasmic inclusions in infected cells in culture and tissues from diseased snakes. In total, viral RNA was detected in 6/8 confirmed IBD cases and 0/18 controls. These viruses have a typical arenavirus genome organization but are highly divergent, belonging to a lineage separate from that of the Old and New World arenaviruses. Furthermore, these viruses encode envelope glycoproteins that are more similar to those of filoviruses than to those of other arenaviruses. These findings implicate these viruses as candidate etiologic agents of IBD. The presence of arenaviruses outside mammals reveals that these viruses infect an unexpectedly broad range of species and represent a new reservoir of potential human pathogens.",2012 Aug 14,"['Stenglein, Mark D.', 'Sanders, Chris', 'Kistler, Amy L.', 'Ruby, J. Graham', 'Franco, Jessica Y.', 'Reavill, Drury R.', 'Dunker, Freeland', 'DeRisi, Joseph L.']",mBio,,,False
eec44b63232c7b965ed908e716003135f358ab57,PMC,The impact of multiple infections on wild animal hosts: a review,http://dx.doi.org/10.3402/iee.v1i0.7346,PMC3426331,22957114,CC BY-NC,"Field parasitological studies consistently demonstrate the reality of polyparasitism in natural systems. However, only recently, studies from ecological and evolutionary fields have emphasised a broad spectrum of potential multiple infections-related impacts. The main goal of our review is to reunify the different approaches on the impacts of polyparasitism, not only from laboratory or human medical studies but also from field or theoretical studies. We put forward that ecological and epidemiological determinants to explain the level of polyparasitism, which regularly affects not only host body condition, survival or reproduction but also host metabolism, genetics or immune investment. Despite inherent limitations of all these studies, multiple infections should be considered more systematically in wildlife to better appreciate the importance of parasite diversity in wildlife, cumulative effects of parasitism on the ecology and evolution of their hosts.",2011 Sep 19,"['Bordes, Frédéric', 'Morand, Serge']",Infect Ecol Epidemiol,,,True
2ffddf5caaef38207b58710a93ee8361518813c9,PMC,The need for one health degree programs,http://dx.doi.org/10.3402/iee.v1i0.7919,PMC3426340,22957121,CC BY-NC,"This commentary offers suggestions for improving public health and public health education by emphasizing One Health principles, the integrating of human, veterinary, and environmental sciences. One Health is increasingly recognized as a powerful approach to the prevention and control of zoonotic diseases, increasing food productivity and safety, improving biosecurity, and enhancing many areas of biomedical research.",2011 Jul 14,"Kahn, Laura H.",Infect Ecol Epidemiol,,,True
7acb13da2225f2c681714a69df8d7787d3312203,PMC,"Emerging Zoonoses: the ""One Health Approach""",http://dx.doi.org/10.5491/SHAW.2012.3.1.77,PMC3430925,22953235,CC BY-NC,"Zoonoses represent a public health risk recently pointed out by the spreading of previously unknown human infectious diseases emerging from animal reservoirs such as severe acute respiratory syndrome and avian influenza caused by H5N1-virus. These outbreaks have shown that animal breeding activities can pose a significant public health risk. Until now, the risk of zoonoses has probably been underestimated, particularly in occupational settings. The emergence or re-emergence of bacterial (Mycobacterium bovis and Brucella spp) or viral (hepatitis E virus) infections shows that zoonoses should be considered as emerging risks in agricultural and animal breeding and should be addressed by specific preventive interventions. Close cooperation and interaction between veterinarians, occupational health physicians and public health operators is necessary, for a worldwide strategy to expand interdisciplinary collaborations and communications in all aspects of health care for humans, animals and the environment. This is what the One Health Approach was intended to be.",2012 Mar 8,"['Rabozzi, Giulia', 'Bonizzi, Luigi', 'Crespi, Eleonora', 'Somaruga, Chiara', 'Sokooti, Maryam', 'Tabibi, Ramin', 'Vellere, Francesca', 'Brambilla, Gabri', 'Colosio, Claudio']",Saf Health Work,,,True
2eefde0ef2d54748b892970703c15b798192274e,PMC,"Personal, Occupational, and Public Health Perspectives on Dealing with the First Case of Influenza A (H1N1) in the United Arab Emirates",http://dx.doi.org/10.5491/SHAW.2011.2.1.83,PMC3431893,22953191,CC BY-NC,"New epidemics of infectious diseases often involve health care workers. In this short communication we present a case report of a health care professional who became the first case of influenza H1N1 virus to be notified in the United Arab Emirates. There are several issues related to workplace considerations and general public health, including preventive measures, the need for isolation of the patient, dealing with contacts, return to work, and communication with the workforce.",2011 Mar 31,"['Shah, Syed M.', 'Aw, Tar-Ching', 'Blair, Iain', 'Hashmey, Rayhan', 'Sheek-Hussein, Mahmoud']",Saf Health Work,,,True
37ab0d36dd92298368b797e0770ebfa03a36eca8,PMC,"Pip6-PMO, A New Generation of Peptide-oligonucleotide Conjugates With Improved Cardiac Exon Skipping Activity for DMD Treatment",http://dx.doi.org/10.1038/mtna.2012.30,PMC3438601,23344180,CC BY-NC-ND,"Antisense oligonucleotides (AOs) are currently the most promising therapeutic intervention for Duchenne muscular dystrophy (DMD). AOs modulate dystrophin pre-mRNA splicing, thereby specifically restoring the dystrophin reading frame and generating a truncated but semifunctional dystrophin protein. Challenges in the development of this approach are the relatively poor systemic AO delivery and inefficient dystrophin correction in affected non-skeletal muscle tissues, including the heart. We have previously reported impressive heart activity including high-splicing efficiency and dystrophin restoration following a single administration of an arginine-rich cell-penetrating peptide (CPPs) conjugated to a phosphorodiamidate morpholino oligonucleotide (PMO): Pip5e-PMO. However, the mechanisms underlying this activity are poorly understood. Here, we report studies involving single dose administration (12.5 mg/kg) of derivatives of Pip5e-PMO, consecutively assigned as Pip6-PMOs. These peptide-PMOs comprise alterations to the central hydrophobic core of the Pip5e peptide and illustrate that certain changes to the peptide sequence improves its activity; however, partial deletions within the hydrophobic core abolish its efficiency. Our data indicate that the hydrophobic core of the Pip sequences is critical for PMO delivery to the heart and that specific modifications to this region can enhance activity further. The results have implications for therapeutic PMO development for DMD.",2012 Aug 14,"['Betts, Corinne', 'Saleh, Amer F', 'Arzumanov, Andrey A', 'Hammond, Suzan M', 'Godfrey, Caroline', 'Coursindel, Thibault', 'Gait, Michael J', 'Wood, Matthew JA']",Mol Ther Nucleic Acids,,,True
7aece0f190a58b3838b7662ad8958a5ed4a8f4f0,PMC,"Pip6-PMO, A New Generation of Peptide-oligonucleotide Conjugates With Improved Cardiac Exon Skipping Activity for DMD Treatment",http://dx.doi.org/10.1038/mtna.2012.30,PMC3438601,23344180,CC BY-NC-ND,"Antisense oligonucleotides (AOs) are currently the most promising therapeutic intervention for Duchenne muscular dystrophy (DMD). AOs modulate dystrophin pre-mRNA splicing, thereby specifically restoring the dystrophin reading frame and generating a truncated but semifunctional dystrophin protein. Challenges in the development of this approach are the relatively poor systemic AO delivery and inefficient dystrophin correction in affected non-skeletal muscle tissues, including the heart. We have previously reported impressive heart activity including high-splicing efficiency and dystrophin restoration following a single administration of an arginine-rich cell-penetrating peptide (CPPs) conjugated to a phosphorodiamidate morpholino oligonucleotide (PMO): Pip5e-PMO. However, the mechanisms underlying this activity are poorly understood. Here, we report studies involving single dose administration (12.5 mg/kg) of derivatives of Pip5e-PMO, consecutively assigned as Pip6-PMOs. These peptide-PMOs comprise alterations to the central hydrophobic core of the Pip5e peptide and illustrate that certain changes to the peptide sequence improves its activity; however, partial deletions within the hydrophobic core abolish its efficiency. Our data indicate that the hydrophobic core of the Pip sequences is critical for PMO delivery to the heart and that specific modifications to this region can enhance activity further. The results have implications for therapeutic PMO development for DMD.",2012 Aug 14,"['Betts, Corinne', 'Saleh, Amer F', 'Arzumanov, Andrey A', 'Hammond, Suzan M', 'Godfrey, Caroline', 'Coursindel, Thibault', 'Gait, Michael J', 'Wood, Matthew JA']",Mol Ther Nucleic Acids,,,False
dafb5ac136c6784c756a2f7f1c4e36b72b3dd085,PMC,"Pip6-PMO, A New Generation of Peptide-oligonucleotide Conjugates With Improved Cardiac Exon Skipping Activity for DMD Treatment",http://dx.doi.org/10.1038/mtna.2012.30,PMC3438601,23344180,CC BY-NC-ND,"Antisense oligonucleotides (AOs) are currently the most promising therapeutic intervention for Duchenne muscular dystrophy (DMD). AOs modulate dystrophin pre-mRNA splicing, thereby specifically restoring the dystrophin reading frame and generating a truncated but semifunctional dystrophin protein. Challenges in the development of this approach are the relatively poor systemic AO delivery and inefficient dystrophin correction in affected non-skeletal muscle tissues, including the heart. We have previously reported impressive heart activity including high-splicing efficiency and dystrophin restoration following a single administration of an arginine-rich cell-penetrating peptide (CPPs) conjugated to a phosphorodiamidate morpholino oligonucleotide (PMO): Pip5e-PMO. However, the mechanisms underlying this activity are poorly understood. Here, we report studies involving single dose administration (12.5 mg/kg) of derivatives of Pip5e-PMO, consecutively assigned as Pip6-PMOs. These peptide-PMOs comprise alterations to the central hydrophobic core of the Pip5e peptide and illustrate that certain changes to the peptide sequence improves its activity; however, partial deletions within the hydrophobic core abolish its efficiency. Our data indicate that the hydrophobic core of the Pip sequences is critical for PMO delivery to the heart and that specific modifications to this region can enhance activity further. The results have implications for therapeutic PMO development for DMD.",2012 Aug 14,"['Betts, Corinne', 'Saleh, Amer F', 'Arzumanov, Andrey A', 'Hammond, Suzan M', 'Godfrey, Caroline', 'Coursindel, Thibault', 'Gait, Michael J', 'Wood, Matthew JA']",Mol Ther Nucleic Acids,,,False
34b9b4a8e608307dc712cdb1ad0ac9d098b1d77e,PMC,"Pip6-PMO, A New Generation of Peptide-oligonucleotide Conjugates With Improved Cardiac Exon Skipping Activity for DMD Treatment",http://dx.doi.org/10.1038/mtna.2012.30,PMC3438601,23344180,CC BY-NC-ND,"Antisense oligonucleotides (AOs) are currently the most promising therapeutic intervention for Duchenne muscular dystrophy (DMD). AOs modulate dystrophin pre-mRNA splicing, thereby specifically restoring the dystrophin reading frame and generating a truncated but semifunctional dystrophin protein. Challenges in the development of this approach are the relatively poor systemic AO delivery and inefficient dystrophin correction in affected non-skeletal muscle tissues, including the heart. We have previously reported impressive heart activity including high-splicing efficiency and dystrophin restoration following a single administration of an arginine-rich cell-penetrating peptide (CPPs) conjugated to a phosphorodiamidate morpholino oligonucleotide (PMO): Pip5e-PMO. However, the mechanisms underlying this activity are poorly understood. Here, we report studies involving single dose administration (12.5 mg/kg) of derivatives of Pip5e-PMO, consecutively assigned as Pip6-PMOs. These peptide-PMOs comprise alterations to the central hydrophobic core of the Pip5e peptide and illustrate that certain changes to the peptide sequence improves its activity; however, partial deletions within the hydrophobic core abolish its efficiency. Our data indicate that the hydrophobic core of the Pip sequences is critical for PMO delivery to the heart and that specific modifications to this region can enhance activity further. The results have implications for therapeutic PMO development for DMD.",2012 Aug 14,"['Betts, Corinne', 'Saleh, Amer F', 'Arzumanov, Andrey A', 'Hammond, Suzan M', 'Godfrey, Caroline', 'Coursindel, Thibault', 'Gait, Michael J', 'Wood, Matthew JA']",Mol Ther Nucleic Acids,,,False
603a0f4e1455395829489569b5c975f6c7858d34,PMC,"Pip6-PMO, A New Generation of Peptide-oligonucleotide Conjugates With Improved Cardiac Exon Skipping Activity for DMD Treatment",http://dx.doi.org/10.1038/mtna.2012.30,PMC3438601,23344180,CC BY-NC-ND,"Antisense oligonucleotides (AOs) are currently the most promising therapeutic intervention for Duchenne muscular dystrophy (DMD). AOs modulate dystrophin pre-mRNA splicing, thereby specifically restoring the dystrophin reading frame and generating a truncated but semifunctional dystrophin protein. Challenges in the development of this approach are the relatively poor systemic AO delivery and inefficient dystrophin correction in affected non-skeletal muscle tissues, including the heart. We have previously reported impressive heart activity including high-splicing efficiency and dystrophin restoration following a single administration of an arginine-rich cell-penetrating peptide (CPPs) conjugated to a phosphorodiamidate morpholino oligonucleotide (PMO): Pip5e-PMO. However, the mechanisms underlying this activity are poorly understood. Here, we report studies involving single dose administration (12.5 mg/kg) of derivatives of Pip5e-PMO, consecutively assigned as Pip6-PMOs. These peptide-PMOs comprise alterations to the central hydrophobic core of the Pip5e peptide and illustrate that certain changes to the peptide sequence improves its activity; however, partial deletions within the hydrophobic core abolish its efficiency. Our data indicate that the hydrophobic core of the Pip sequences is critical for PMO delivery to the heart and that specific modifications to this region can enhance activity further. The results have implications for therapeutic PMO development for DMD.",2012 Aug 14,"['Betts, Corinne', 'Saleh, Amer F', 'Arzumanov, Andrey A', 'Hammond, Suzan M', 'Godfrey, Caroline', 'Coursindel, Thibault', 'Gait, Michael J', 'Wood, Matthew JA']",Mol Ther Nucleic Acids,,,False
8c4a02b6cce4a9bb38191e75f01201680236b993,PMC,"Pip6-PMO, A New Generation of Peptide-oligonucleotide Conjugates With Improved Cardiac Exon Skipping Activity for DMD Treatment",http://dx.doi.org/10.1038/mtna.2012.30,PMC3438601,23344180,CC BY-NC-ND,"Antisense oligonucleotides (AOs) are currently the most promising therapeutic intervention for Duchenne muscular dystrophy (DMD). AOs modulate dystrophin pre-mRNA splicing, thereby specifically restoring the dystrophin reading frame and generating a truncated but semifunctional dystrophin protein. Challenges in the development of this approach are the relatively poor systemic AO delivery and inefficient dystrophin correction in affected non-skeletal muscle tissues, including the heart. We have previously reported impressive heart activity including high-splicing efficiency and dystrophin restoration following a single administration of an arginine-rich cell-penetrating peptide (CPPs) conjugated to a phosphorodiamidate morpholino oligonucleotide (PMO): Pip5e-PMO. However, the mechanisms underlying this activity are poorly understood. Here, we report studies involving single dose administration (12.5 mg/kg) of derivatives of Pip5e-PMO, consecutively assigned as Pip6-PMOs. These peptide-PMOs comprise alterations to the central hydrophobic core of the Pip5e peptide and illustrate that certain changes to the peptide sequence improves its activity; however, partial deletions within the hydrophobic core abolish its efficiency. Our data indicate that the hydrophobic core of the Pip sequences is critical for PMO delivery to the heart and that specific modifications to this region can enhance activity further. The results have implications for therapeutic PMO development for DMD.",2012 Aug 14,"['Betts, Corinne', 'Saleh, Amer F', 'Arzumanov, Andrey A', 'Hammond, Suzan M', 'Godfrey, Caroline', 'Coursindel, Thibault', 'Gait, Michael J', 'Wood, Matthew JA']",Mol Ther Nucleic Acids,,,False
416c2b1c9548c3f4401c419fd2e72285083c1c1c,PMC,"Pip6-PMO, A New Generation of Peptide-oligonucleotide Conjugates With Improved Cardiac Exon Skipping Activity for DMD Treatment",http://dx.doi.org/10.1038/mtna.2012.30,PMC3438601,23344180,CC BY-NC-ND,"Antisense oligonucleotides (AOs) are currently the most promising therapeutic intervention for Duchenne muscular dystrophy (DMD). AOs modulate dystrophin pre-mRNA splicing, thereby specifically restoring the dystrophin reading frame and generating a truncated but semifunctional dystrophin protein. Challenges in the development of this approach are the relatively poor systemic AO delivery and inefficient dystrophin correction in affected non-skeletal muscle tissues, including the heart. We have previously reported impressive heart activity including high-splicing efficiency and dystrophin restoration following a single administration of an arginine-rich cell-penetrating peptide (CPPs) conjugated to a phosphorodiamidate morpholino oligonucleotide (PMO): Pip5e-PMO. However, the mechanisms underlying this activity are poorly understood. Here, we report studies involving single dose administration (12.5 mg/kg) of derivatives of Pip5e-PMO, consecutively assigned as Pip6-PMOs. These peptide-PMOs comprise alterations to the central hydrophobic core of the Pip5e peptide and illustrate that certain changes to the peptide sequence improves its activity; however, partial deletions within the hydrophobic core abolish its efficiency. Our data indicate that the hydrophobic core of the Pip sequences is critical for PMO delivery to the heart and that specific modifications to this region can enhance activity further. The results have implications for therapeutic PMO development for DMD.",2012 Aug 14,"['Betts, Corinne', 'Saleh, Amer F', 'Arzumanov, Andrey A', 'Hammond, Suzan M', 'Godfrey, Caroline', 'Coursindel, Thibault', 'Gait, Michael J', 'Wood, Matthew JA']",Mol Ther Nucleic Acids,,,False
e1ca13fb1fabab727830bd615d92049fc6502383,PMC,"Murphy's law—if anything can go wrong, it will: Problems in phage electron microscopy",http://dx.doi.org/10.4161/bact.20693,PMC3442825,23050222,CC BY-NC,"The quality of bacteriophage electron microscopy appears to be on a downward course since the 1980s. This coincides with the introduction of digital electron microscopes and a general lowering of standards, possibly due to the disappearance of several world-class electron microscopists The most important problem seems to be poor contrast. Positive staining is frequently not recognized as an undesirable artifact. Phage parts, bacterial debris, and aberrant or damaged phage particles may be misdiagnosed as bacterial viruses. Digital electron microscopes often seem to be operated without magnification control because this is difficult and inconvenient. In summary, most phage electron microscopy problems may be attributed to human failure. Journals are a last-ditch defense and have a heavy responsibility in selecting competent reviewers and rejecting, or not, unsatisfactory articles.",2012 Apr 1,"['Ackermann, Hans-W.', 'Tiekotter, Kenneth L.']",Bacteriophage,,,True
c916af477a30ec5209caed9b99ce18f5aebdd7c1,PMC,"Murphy's law—if anything can go wrong, it will: Problems in phage electron microscopy",http://dx.doi.org/10.4161/bact.20693,PMC3442825,23050222,CC BY-NC,"The quality of bacteriophage electron microscopy appears to be on a downward course since the 1980s. This coincides with the introduction of digital electron microscopes and a general lowering of standards, possibly due to the disappearance of several world-class electron microscopists The most important problem seems to be poor contrast. Positive staining is frequently not recognized as an undesirable artifact. Phage parts, bacterial debris, and aberrant or damaged phage particles may be misdiagnosed as bacterial viruses. Digital electron microscopes often seem to be operated without magnification control because this is difficult and inconvenient. In summary, most phage electron microscopy problems may be attributed to human failure. Journals are a last-ditch defense and have a heavy responsibility in selecting competent reviewers and rejecting, or not, unsatisfactory articles.",2012 Apr 1,"['Ackermann, Hans-W.', 'Tiekotter, Kenneth L.']",Bacteriophage,,,False
06137bb1e53080493b33c1b749b59848cddc05fc,PMC,Spacer-length dependence of programmed −1 or −2 ribosomal frameshifting on a U(6)A heptamer supports a role for messenger RNA (mRNA) tension in frameshifting,http://dx.doi.org/10.1093/nar/gks629,PMC3458567,22743270,CC BY-NC,"Programmed −1 ribosomal frameshifting is employed in the expression of a number of viral and cellular genes. In this process, the ribosome slips backwards by a single nucleotide and continues translation of an overlapping reading frame, generating a fusion protein. Frameshifting signals comprise a heptanucleotide slippery sequence, where the ribosome changes frame, and a stimulatory RNA structure, a stem–loop or RNA pseudoknot. Antisense oligonucleotides annealed appropriately 3′ of a slippery sequence have also shown activity in frameshifting, at least in vitro. Here we examined frameshifting at the U(6)A slippery sequence of the HIV gag/pol signal and found high levels of both −1 and −2 frameshifting with stem–loop, pseudoknot or antisense oligonucleotide stimulators. By examining −1 and −2 frameshifting outcomes on mRNAs with varying slippery sequence-stimulatory RNA spacing distances, we found that −2 frameshifting was optimal at a spacer length 1–2 nucleotides shorter than that optimal for −1 frameshifting with all stimulatory RNAs tested. We propose that the shorter spacer increases the tension on the mRNA such that when the tRNA detaches, it more readily enters the −2 frame on the U(6)A heptamer. We propose that mRNA tension is central to frameshifting, whether promoted by stem–loop, pseudoknot or antisense oligonucleotide stimulator.",2012 Sep 28,"['Lin, Zhaoru', 'Gilbert, Robert J. C.', 'Brierley, Ian']",Nucleic Acids Res,,,True
ac50b9faf4e811ff32603511ecdeee8e8d1eb897,PMC,Spacer-length dependence of programmed −1 or −2 ribosomal frameshifting on a U(6)A heptamer supports a role for messenger RNA (mRNA) tension in frameshifting,http://dx.doi.org/10.1093/nar/gks629,PMC3458567,22743270,CC BY-NC,"Programmed −1 ribosomal frameshifting is employed in the expression of a number of viral and cellular genes. In this process, the ribosome slips backwards by a single nucleotide and continues translation of an overlapping reading frame, generating a fusion protein. Frameshifting signals comprise a heptanucleotide slippery sequence, where the ribosome changes frame, and a stimulatory RNA structure, a stem–loop or RNA pseudoknot. Antisense oligonucleotides annealed appropriately 3′ of a slippery sequence have also shown activity in frameshifting, at least in vitro. Here we examined frameshifting at the U(6)A slippery sequence of the HIV gag/pol signal and found high levels of both −1 and −2 frameshifting with stem–loop, pseudoknot or antisense oligonucleotide stimulators. By examining −1 and −2 frameshifting outcomes on mRNAs with varying slippery sequence-stimulatory RNA spacing distances, we found that −2 frameshifting was optimal at a spacer length 1–2 nucleotides shorter than that optimal for −1 frameshifting with all stimulatory RNAs tested. We propose that the shorter spacer increases the tension on the mRNA such that when the tRNA detaches, it more readily enters the −2 frame on the U(6)A heptamer. We propose that mRNA tension is central to frameshifting, whether promoted by stem–loop, pseudoknot or antisense oligonucleotide stimulator.",2012 Sep 28,"['Lin, Zhaoru', 'Gilbert, Robert J. C.', 'Brierley, Ian']",Nucleic Acids Res,,,False
39a01111cbf00eb9bf55c7713c1edec443d3e97e,PMC,Describing the Chinese HIV Surveillance System and the Influences of Political Structures and Social Stigma,http://dx.doi.org/10.2174/1874613601206010163,PMC3462331,23049665,CC BY-NC,"China’s public health surveillance system for HIV was established in late 1980s and has evolved significantly during the past three decades. With the gradually changing mode of HIV transmission from sharing of intravenous injecting equipment to sexual exposure and the rapid spread of HIV infection among Chinese homosexual men in recent years, an efficient and comprehensive population-level surveillance system for describing epidemics trends and risk behaviours associated with HIV acquisition are essential for effective public health interventions for HIV. The current review describes the overall strength of the Chinese HIV surveillance system and its structural weaknesses from a political and social perspective. The HIV surveillance system in China has undergone substantial revamping leading to a comprehensive, timely and efficient reporting system. However, large data gaps and lack of quality control and sharing of information obstruct the full performance of the system. This is largely due to fragmented authoritarianism brought about by the underlying political structure. Social stigma and discrimination in health institutes are also key barriers for further improvements of HIV diagnosis and surveillance in China.",2012 Sep 7,"['Zhang, Lei', 'Fung Chow, Eric Pui', 'Zhang, Jun', 'Jing, Jun', 'Wilson, David P']",Open AIDS J,,,True
71cb2319da3251ef1b4bc99ce5c4ca633b2cb1b9,PMC,Genomics and Public Health Research: Can the State Allow Access to Genomic Databases?,,PMC3468988,23113174,CC BY-NC,"Because many diseases are multifactorial disorders, the scientific progress in genomics and genetics should be taken into consideration in public health research. In this context, genomic databases will constitute an important source of information. Consequently, it is important to identify and characterize the State’s role and authority on matters related to public health, in order to verify whether it has access to such databases while engaging in public health genomic research. We first consider the evolution of the concept of public health, as well as its core functions, using a comparative approach (e.g. WHO, PAHO, CDC and the Canadian province of Quebec). Following an analysis of relevant Quebec legislation, the precautionary principle is examined as a possible avenue to justify State access to and use of genomic databases for research purposes. Finally, we consider the Influenza pandemic plans developed by WHO, Canada, and Quebec, as examples of key tools framing public health decision-making process. We observed that State powers in public health, are not, in Quebec, well adapted to the expansion of genomics research. We propose that the scope of the concept of research in public health should be clear and include the following characteristics: a commitment to the health and well-being of the population and to their determinants; the inclusion of both applied research and basic research; and, an appropriate model of governance (authorization, follow-up, consent, etc.). We also suggest that the strategic approach version of the precautionary principle could guide collective choices in these matters.",2012 May 31,"['Cousineau, J', 'Girard, N', 'Monardes, C', 'Leroux, T', 'Jean, M Stanton']",Iran J Public Health,,,True
c94cf364c4ceb68d6b7b7cbc252d32a53401779a,PMC,The Singapore Field Epidemiology Service: Insights Into Outbreak Management,http://dx.doi.org/10.3961/jpmph.2012.45.5.277,PMC3469809,23091652,CC BY-NC,"Field epidemiology involves the implementation of quick and targeted public health interventions with the aid of epidemiological methods. In this article, we share our practical experiences in outbreak management and in safeguarding the population against novel diseases. Given that cities represent the financial nexuses of the global economy, global health security necessitates the safeguard of cities against epidemic diseases. Singapore's public health landscape has undergone a systemic and irreversible shift with global connectivity, rapid urbanization, ecological change, increased affluence, as well as shifting demographic patterns over the past two decades. Concomitantly, the threat of epidemics, ranging from severe acute respiratory syndrome and influenza A (H1N1) to the resurgence of vector-borne diseases as well as the rise of modern lifestyle-related outbreaks, have worsened difficulties in safeguarding public health amidst much elusiveness and unpredictability. One critical factor that has helped the country overcome these innate and man-made public health vulnerabilities is the development of a resilient field epidemiology service, which includes our enhancement of surveillance and response capacities for outbreak management, and investment in public health leadership. We offer herein the Singapore story as a case study in meeting the challenges of disease control in our modern built environment.",2012 Sep 28,"['Ooi, Peng-Lim', 'Seetoh, Theresa', 'Cutter, Jeffery']",J Prev Med Public Health,,,True
1b58422e266ab9339c919119923229d080f27360,PMC,ACE/ACE2 Ratio and MMP-9 Activity as Potential Biomarkers in Tuberculous Pleural Effusions,http://dx.doi.org/10.7150/ijbs.5087,PMC3477689,23091417,CC BY-NC-ND,"Objective: Pleural effusion is common problem, but the rapid and reliable diagnosis for specific pathogenic effusions are lacking. This study aimed to identify the diagnosis based on clinical variables to differentiate pleural tuberculous exudates from other pleural effusions. We also investigated the role of renin-angiotensin system (RAS) and matrix metalloproteinase (MMPs) in the pathogenesis of pleural exudates. Experimental design: The major components in RAS and extracellular matrix metabolism, including angiotensin converting enzyme (ACE), ACE2, MMP-2 and MMP-9 activities, were measured and compared in the patients with transudative (n = 45) and exudative (n = 80) effusions. The exudative effusions were come from the patients with tuberculosis (n = 20), pneumonia (n = 32), and adenocarcinoma (n = 28). Results: Increased ACE and equivalent ACE2 activities, resulting in a significantly increased ACE/ACE2 ratio in exudates, were detected compared to these values in transudates. MMP-9 activity in exudates was significantly higher than that in transudates. The significant correlation between ACE and ACE2 activity that was found in transudates was not found in exudates. Advanced analyses showed significantly increased ACE and MMP-9 activities, and decreased ACE2 activity in tuberculous pleural effusions compared with those in pneumonia and adenocarcinoma effusions. The results indicate that increased ACE and MMP-9 activities found in the exudates were mainly contributed from a higher level of both enzyme activities in the tuberculous pleural effusions. Conclusion: Interplay between ACE and ACE2, essential functions in the RAS, and abnormal regulation of MMP-9 probably play a pivotal role in the development of exudative effusions. Moreover, the ACE/ACE2 ratio combined with MMP-9 activity in pleural fluid may be potential biomarkers for diagnosing tuberculous pleurisy.",2012 Oct 17,"['Hsieh, Wen-Yeh', 'Kuan, Tang-Ching', 'Cheng, Kun-Shan', 'Liao, Yan-Chiou', 'Chen, Mu-Yuan', 'Lin, Pei-Heng', 'Hsu, Yuan-Chang', 'Huang, Chen-Yi', 'Hsu, Wei-Hua', 'Yu, Sheng-Yao', 'Lin, Chih-Sheng']",Int J Biol Sci,,,True
632bcacf9702ee34c5424827ab7e5449dd21ddcf,PMC,First Report of Respiratory Syncytial Virus and Human Metapneumovirus Co-Infection in a 2-Year-Old Kawasaki Patient in Iran,,PMC3481691,23113048,CC BY-NC,"BACKGROUND: Respiratory virus infections in children are a leading cause of morbidity and mortality worldwide. METHODS: A total of 897 clinical specimens were collected from February 2007 to January 2008 and transported to the National Influenza Center. Two hundred and two samples belonged to children under the age of six from 897 specimens, described above, were selected. Then they were tested for influenza virus types and subtypes by real time PCR assay subsequently, the specimens were tested for RSV and hMPV by hemi-nested multiplex PCR and parainfluenza viruses type 1–4 by hemi-nested multiplex PCR and adenovirus by hemi-nested PCR. RESULTS: The throat swab was taken from the Kawasaki case with the history of chicken’s contact. The specimen was tested for all influenza subtypes especially H5N1 and the results were negative. Meanwhile PCR was done for screening of other respiratory viruses that results came out positive for RSV and hMPV. CONCLUSION: In the present study, we demonstrated the possibility to detect dual infection caused by RSV and hMPV, but because of the extravagant pattern of this case, more investigation is suggested specially on Kawasaki patients.",2010 Dec 31,"['Shatizadeh Malekshahi, S', 'Mokhtari Azad, T', 'Shahmahmoodi, Sh', 'Yavarian, J', 'Rezaei, F', 'Naseri, M']",Iran J Public Health,,,True
ab58c54193c5257b96d0d8e098fb18d7e2d8d081,PMC,"Birth Defects Data from Surveillance Hospitals in Hubei Province, China, 200l – 2008",,PMC3481713,23113146,CC BY-NC,"BACKGROUND: To determine the prevalence and characteristics of birth defects in perinatal infants in Hubei Province during 200l–2008. METHODS: The prevalence of birth defects in perinatal infants delivered after 28 weeks or more was analyzed in Hubei surveillance hospitals during 200l–2008. RESULTS: The incidence of birth defects in perinatal infants from 200l to 2008 was 120.0 per 10,000 births, and was increased by about 41% from 81. 1 in 2001 to 138.5 per 10,000 births in 2008. The incidence in the first 4 years (2005–2008) was much higher than the latter four (2001–2004) (χ(2)=77.64, P <0.05). The difference in prevalence between urban and rural was of no significance in 2008 (χ(2)=0.03, P >0.05), but that between male and female was significant (χ(2)=5.24, P <0.05), as the former prevalence was much higher. The prevalence of birth defects was slightly higher among mothers over 35 years old than those under 35 years old, but with no significance (χ(2)=1.98, P >0.05). The two leading birth defects were cleft lip and/or palate and polydactyly, followed by congenital heart disease, hydrocephaly, external ear malformation and neural tube defects. The prevalence of congenital heart disease was rising. CONCLUSIONS: Eight years’ birth defects data indicate that the birth defect rate was on the rise and the birth defects prevalence in Hubei province should be valued.",2012 Mar 31,"['Tu, Lh', 'Li, H', 'Zhang, Hp', 'Li, Xd', 'Lin, Jj', 'Xiong, Cl']",Iran J Public Health,,,True
766b9c02fdb5aaeee2c3a399ae9a6d5e179eca8f,PMC,Biocontainment in Gain-of-Function Infectious Disease Research,http://dx.doi.org/10.1128/mBio.00290-12,PMC3484385,23047747,CC BY-NC-SA,"The discussion of H5N1 influenza virus gain-of-function research has focused chiefly on its risk-to-benefit ratio. Another key component of risk is the level of containment employed. Work is more expensive and less efficient when pursued at biosafety level 4 (BSL-4) than at BSL-3 or at BSL-3 as modified for work with agricultural pathogens (BSL-3-Ag). However, here too a risk-to-benefit ratio analysis is applicable. BSL-4 procedures mandate daily inspection of facilities and equipment, monitoring of personnel for signs and symptoms of disease, and logs of dates and times that personnel, equipment, supplies, and samples enter and exit containment. These measures are not required at BSL-3 or BSL-3-Ag. Given the implications of inadvertent or deliberate release of high-threat pathogens with pandemic potential, it is imperative that the World Health Organization establish strict criteria for biocontainment that can be fairly applied in the developing world, as well as in more economically developed countries.",2012 Oct 9,"Lipkin, W. Ian",mBio,,,True
7ec5f725610673671e1703613932224d6494e880,PMC,Rethinking Biosafety in Research on Potential Pandemic Pathogens,http://dx.doi.org/10.1128/mBio.00360-12,PMC3484391,23047752,CC BY-NC-SA,"If accidentally released, mammalian-transmissible influenza A/H5N1 viruses could pose a greater threat to public health than possibly any other infectious agent currently under study in laboratories, because of such viruses’ likely combination of transmissibility and virulence to humans. We advocate explicit risk-benefit assessments before work on such pathogens is permitted or funded, improvement of biosafety practices and enforcement, and harmonization of criteria for permitting such experiments across government agencies, as well as internationally. Such potential pandemic pathogens, as they have been called, jeopardize not only laboratory workers and their contacts, but also the wider population, who should be involved in assessments of when such risks are acceptable in the service of scientific knowledge that may itself bear major public health benefits.",2012 Oct 9,"['Lipsitch, Marc', 'Bloom, Barry R.']",mBio,,,True
b3f6786ea67c035d20928aa4cb7eb6b9d853adb7,PMC,Evaluation of a Multiplex Real-time PCR Assay for the Detection of Respiratory Viruses in Clinical Specimens,http://dx.doi.org/10.3343/alm.2012.32.6.399,PMC3486933,23130338,CC BY-NC,"BACKGROUND: In this study, we evaluated the analytical performance and clinical potential of a one-step multiplex real-time PCR assay for the simultaneous detection of 14 types of respiratory viruses using the AdvanSure RV real-time PCR Kit (LG Life Sciences, Korea). METHODS: Three hundred and twenty clinical specimens were tested with the AdvanSure RV real-time PCR Kit and conventional multiplex reverse transcription (RT)-PCR assay. The assay results were analyzed and the one-step AdvanSure RV real-time PCR Kit was compared with the conventional multiplex RT-PCR assay with respect to the sensitivity and specificity of the detection of respiratory viruses. RESULTS: The limit of detection (LOD) was 1.31 plaque-forming units (PFU)/mL for human rhinoviruses (hRVs), 4.93 PFU/mL for human coronavirus HCoV-229E/NL63, 2.67 PFU/mL for human coronavirus HCoV-OC43, 18.20 PFU/mL for parainfluenza virus 1 (PIV)-1, 24.57 PFU/mL for PIV-2, 1.73 PFU/mL for PIV-3, 1.79 PFU/mL for influenza virus group (Flu) A, 59.51 PFU/mL for FluB, 5.46 PFU/mL for human respiratory syncytial virus (hRSV)-A, 17.23 PFU/mL for hRSV-B, 9.99 PFU/mL for human adenovirus (ADVs). The cross-reactivity test for this assay against 23 types of non-respiratory viruses showed negative results for all viruses tested. The agreement between the one-step AdvanSure multiplex real-time PCR assay and the conventional multiplex RT-PCR assay was 98%. CONCLUSIONS: The one-step AdvanSure RV multiplex real-time PCR assay is a simple assay with high potential for specific, rapid and sensitive laboratory diagnosis of respiratory viruses compared to conventional multiplex RT-PCR.",2012 Nov 17,"['Rheem, Insoo', 'Park, Joowon', 'Kim, Tae-Hyun', 'Kim, Jong Wan']",Ann Lab Med,,,True
f8da6bc56b3d7a64f5f0ba9a7928264dc986e43f,PMC,A Single Native Ganglioside GM(1)-Binding Site Is Sufficient for Cholera Toxin To Bind to Cells and Complete the Intoxication Pathway,http://dx.doi.org/10.1128/mBio.00401-12,PMC3487775,23111873,CC BY-NC-SA,"Cholera toxin (CT) from Vibrio cholerae is responsible for the majority of the symptoms of the diarrheal disease cholera. CT is a heterohexameric protein complex with a 240-residue A subunit and a pentameric B subunit of identical 103-residue B polypeptides. The A subunit is proteolytically cleaved within a disulfide-linked loop to generate the A1 and A2 fragments. The B subunit of wild-type (wt) CT binds 5 cell surface ganglioside GM(1) (GM(1)) molecules, and the toxin-GM(1) complex traffics from the plasma membrane (PM) retrograde through endosomes and the Golgi apparatus to the endoplasmic reticulum (ER). From the ER, the enzymatic A1 fragment retrotranslocates to the cytosol to cause disease. Clustering of GM(1) by multivalent toxin binding can structurally remodel cell membranes in ways that may assist toxin uptake and retrograde trafficking. We have recently found, however, that CT may traffic from the PM to the ER by exploiting an endogenous glycosphingolipid pathway (A. A. Wolf et al., Infect. Immun. 76:1476–1484, 2008, and D. J. F. Chinnapen et al., Dev. Cell 23:573–586, 2012), suggesting that multivalent binding to GM(1) is dispensable. Here we formally tested this idea by creating homogenous chimeric holotoxins with defined numbers of native GM(1) binding sites from zero (nonbinding) to five (wild type). We found that a single GM(1) binding site is sufficient for activity of the holotoxin. Therefore, remodeling of cell membranes by mechanisms that involve multivalent binding of toxin to GM(1) receptors is not essential for toxicity of CT.",2012 Oct 30,"['Jobling, Michael G.', 'Yang, ZhiJie', 'Kam, Wendy R.', 'Lencer, Wayne I.', 'Holmes, Randall K.']",mBio,,,True
4ef096e83734058dd9385a5d65b0c63c080df563,PMC,"Crystal structure of RlmM, the 2′O-ribose methyltransferase for C2498 of Escherichia coli 23S rRNA",http://dx.doi.org/10.1093/nar/gks727,PMC3488215,22923526,CC BY-NC,"RlmM (YgdE) catalyzes the S-adenosyl methionine (AdoMet)-dependent 2′O methylation of C2498 in 23S ribosomal RNA (rRNA) of Escherichia coli. Previous experiments have shown that RlmM is active on 23S rRNA from an RlmM knockout strain but not on mature 50S subunits from the same strain. Here, we demonstrate RlmM methyltransferase (MTase) activity on in vitro transcribed 23S rRNA and its domain V. We have solved crystal structures of E. coli RlmM at 1.9 Å resolution and of an RlmM–AdoMet complex at 2.6 Å resolution. RlmM consists of an N-terminal THUMP domain and a C-terminal catalytic Rossmann-like fold MTase domain in a novel arrangement. The catalytic domain of RlmM is closely related to YiiB, TlyA and fibrillarins, with the second K of the catalytic tetrad KDKE shifted by two residues at the C-terminal end of a beta strand compared with most 2′O MTases. The AdoMet-binding site is open and shallow, suggesting that RNA substrate binding may be required to form a conformation needed for catalysis. A continuous surface of conserved positive charge indicates that RlmM uses one side of the two domains and the inter-domain linker to recognize its RNA substrate.",2012 Nov 24,"['Punekar, Avinash S.', 'Shepherd, Tyson R.', 'Liljeruhm, Josefine', 'Forster, Anthony C.', 'Selmer, Maria']",Nucleic Acids Res,,,True
7db910e35a0a22ccef05b0a5b4c9789acfef2daa,PMC,Evolution of Viral Proteins Originated De Novo by Overprinting,http://dx.doi.org/10.1093/molbev/mss179,PMC3494269,22821011,CC BY-NC,"New protein-coding genes can originate either through modification of existing genes or de novo. Recently, the importance of de novo origination has been recognized in eukaryotes, although eukaryotic genes originated de novo are relatively rare and difficult to identify. In contrast, viruses contain many de novo genes, namely those in which an existing gene has been “overprinted” by a new open reading frame, a process that generates a new protein-coding gene overlapping the ancestral gene. We analyzed the evolution of 12 experimentally validated viral genes that originated de novo and estimated their relative ages. We found that young de novo genes have a different codon usage from the rest of the genome. They evolve rapidly and are under positive or weak purifying selection. Thus, young de novo genes might have strain-specific functions, or no function, and would be difficult to detect using current genome annotation methods that rely on the sequence signature of purifying selection. In contrast to young de novo genes, older de novo genes have a codon usage that is similar to the rest of the genome. They evolve slowly and are under stronger purifying selection. Some of the oldest de novo genes evolve under stronger selection pressure than the ancestral gene they overlap, suggesting an evolutionary tug of war between the ancestral and the de novo gene.",2012 Dec 19,"['Sabath, Niv', 'Wagner, Andreas', 'Karlin, David']",Mol Biol Evol,,,True
61610467351ceab87933d94e3c6e487654d316a8,PMC,Evolution of Viral Proteins Originated De Novo by Overprinting,http://dx.doi.org/10.1093/molbev/mss179,PMC3494269,22821011,CC BY-NC,"New protein-coding genes can originate either through modification of existing genes or de novo. Recently, the importance of de novo origination has been recognized in eukaryotes, although eukaryotic genes originated de novo are relatively rare and difficult to identify. In contrast, viruses contain many de novo genes, namely those in which an existing gene has been “overprinted” by a new open reading frame, a process that generates a new protein-coding gene overlapping the ancestral gene. We analyzed the evolution of 12 experimentally validated viral genes that originated de novo and estimated their relative ages. We found that young de novo genes have a different codon usage from the rest of the genome. They evolve rapidly and are under positive or weak purifying selection. Thus, young de novo genes might have strain-specific functions, or no function, and would be difficult to detect using current genome annotation methods that rely on the sequence signature of purifying selection. In contrast to young de novo genes, older de novo genes have a codon usage that is similar to the rest of the genome. They evolve slowly and are under stronger purifying selection. Some of the oldest de novo genes evolve under stronger selection pressure than the ancestral gene they overlap, suggesting an evolutionary tug of war between the ancestral and the de novo gene.",2012 Dec 19,"['Sabath, Niv', 'Wagner, Andreas', 'Karlin, David']",Mol Biol Evol,,,True
98513efd2f4e86626a263f1eb350ed2702ecb8ec,PMC,Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans,http://dx.doi.org/10.1128/mBio.00473-12,PMC3509437,23170002,CC BY-NC-SA,"A novel human coronavirus (HCoV-EMC/2012) was isolated from a man with acute pneumonia and renal failure in June 2012. This report describes the complete genome sequence, genome organization, and expression strategy of HCoV-EMC/2012 and its relation with known coronaviruses. The genome contains 30,119 nucleotides and contains at least 10 predicted open reading frames, 9 of which are predicted to be expressed from a nested set of seven subgenomic mRNAs. Phylogenetic analysis of the replicase gene of coronaviruses with completely sequenced genomes showed that HCoV-EMC/2012 is most closely related to Tylonycteris bat coronavirus HKU4 (BtCoV-HKU4) and Pipistrellus bat coronavirus HKU5 (BtCoV-HKU5), which prototype two species in lineage C of the genus Betacoronavirus. In accordance with the guidelines of the International Committee on Taxonomy of Viruses, and in view of the 75% and 77% amino acid sequence identity in 7 conserved replicase domains with BtCoV-HKU4 and BtCoV-HKU5, respectively, we propose that HCoV-EMC/2012 prototypes a novel species in the genus Betacoronavirus. HCoV-EMC/2012 may be most closely related to a coronavirus detected in Pipistrellus pipistrellus in The Netherlands, but because only a short sequence from the most conserved part of the RNA-dependent RNA polymerase-encoding region of the genome was reported for this bat virus, its genetic distance from HCoV-EMC remains uncertain. HCoV-EMC/2012 is the sixth coronavirus known to infect humans and the first human virus within betacoronavirus lineage C.",2012 Nov 20,"['van Boheemen, Sander', 'de Graaf, Miranda', 'Lauber, Chris', 'Bestebroer, Theo M.', 'Raj, V. Stalin', 'Zaki, Ali Moh', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.', 'Gorbalenya, Alexander E.', 'Snijder, Eric J.', 'Fouchier, Ron A. M.']",mBio,,,True
d458129464b755df1acadea361d6ea8e18d321b9,PMC,A case of mucolipidosis II presenting with prenatal skeletal dysplasia and severe secondary hyperparathyroidism at birth,http://dx.doi.org/10.3345/kjp.2012.55.11.438,PMC3510274,23227064,CC BY-NC,"Mucolipidosis II (ML II) or inclusion cell disease (I-cell disease) is a rarely occurring autosomal recessive lysosomal enzyme-targeting disease. This disease is usually found to occur in individuals aged between 6 and 12 months, with a clinical phenotype resembling that of Hurler syndrome and radiological findings resembling those of dysostosis multiplex. However, we encountered a rare case of an infant with ML II who presented with prenatal skeletal dysplasia and typical clinical features of severe secondary hyperparathyroidism at birth. A female infant was born at 37(+1) weeks of gestation with a birth weight of 1,690 g (<3rd percentile). Prenatal ultrasonographic findings revealed intrauterine growth retardation and skeletal dysplasia. At birth, the patient had characteristic features of ML II, and skeletal radiographs revealed dysostosis multiplex, similar to rickets. In addition, the patient had high levels of alkaline phosphatase and parathyroid hormone, consistent with severe secondary neonatal hyperparathyroidism. The activities of β-D-hexosaminidase and α-N-acetylglucosaminidase were moderately decreased in the leukocytes but were 5- to 10-fold higher in the plasma. Examination of a placental biopsy specimen showed foamy vacuolar changes in trophoblasts and syncytiotrophoblasts. The diagnosis of ML II was confirmed via GNPTAB genetic testing, which revealed compound heterozygosity of c.3091C>T (p.Arg1031X) and c.3456_3459dupCAAC (p.Ile1154GlnfsX3), the latter being a novel mutation. The infant was treated with vitamin D supplements but expired because of asphyxia at the age of 2 months.",2012 Nov 23,"['Heo, Ju Sun', 'Choi, Ka Young', 'Sohn, Se Hyoung', 'Kim, Curie', 'Kim, Yoon Joo', 'Shin, Seung Han', 'Lee, Jae Myung', 'Lee, Juyoung', 'Sohn, Jin A', 'Lim, Byung Chan', 'Lee, Jin A', 'Choi, Chang Won', 'Kim, Ee-Kyung', 'Kim, Han-Suk', 'Kim, Beyong Il', 'Choi, Jung-Hwan']",Korean J Pediatr,,,True
d311964341e7e167635e150212eee7d7a70130e8,PMC,"A Case of Asymptomatic, Localized, and Idiopathic Diffuse Alveolar Damage",http://dx.doi.org/10.4046/trd.2012.72.4.386,PMC3510291,23227081,CC BY-NC,"Diffuse alveolar damage (DAD) is a histological change in lung tissue, and is generally caused by an acute lung injury, which is characterized by bilateral and widespread damages. Localized DAD occurs very rarely. The causes for DAD are numerous, but the chief cause is acute interstitial pneumonia or acute exacerbation of idiopathic interstitial pneumonia, in cases of idiopathic manifestation. The 82-year-old patient, in this case study, showed a DAD lesion in only 1 lobe. The patient was otherwise healthy, with no previous symptoms of DAD. He was admitted to our medical center owing to localized infiltration, observed on his chest radiograph. Laboratory studies showed no signs of infections. DAD was confirmed by a surgical lung biopsy. The patient received corticosteroid treatment and had gradually improved. We report the case of a patient with localized, idiopathic DAD that cannot be classified as acute interstitial pneumonia or acute exacerbation of idiopathic interstitial pneumonia.",2012 Apr 30,"['Jeon, Young Do', 'Hong, H. Christian', 'Joh, Joon Sung', 'Jung, Ja Young', 'Min, Ji Won', 'Park, Seon Young', 'Lee, Ga Ram']",Tuberc Respir Dis (Seoul),,,True
f86a27f248abc89aef420f88323538086c8b9f8f,PMC,Lentiviral Vector Gene Transfer to Porcine Airways,http://dx.doi.org/10.1038/mtna.2012.47,PMC3511674,23187455,CC BY-NC-ND,"In this study, we investigated lentiviral vector development and transduction efficiencies in well-differentiated primary cultures of pig airway epithelia (PAE) and wild-type pigs in vivo. We noted gene transfer efficiencies similar to that observed for human airway epithelia (HAE). Interestingly, feline immunodeficiency virus (FIV)-based vectors transduced immortalized pig cells as well as pig primary cells more efficiently than HIV-1–based vectors. PAE express TRIM5α, a well-characterized species-specific lentiviral restriction factor. We contrasted the restrictive properties of porcine TRIM5α against FIV- and HIV-based vectors using gain and loss of function approaches. We observed no effect on HIV-1 or FIV conferred transgene expression in response to porcine TRIM5α overexpression or knockdown. To evaluate the ability of GP64-FIV to transduce porcine airways in vivo, we delivered vector expressing mCherry to the tracheal lobe of the lung and the ethmoid sinus of 4-week-old pigs. One week later, epithelial cells expressing mCherry were readily detected. Our findings indicate that pseudotyped FIV vectors confer similar tropisms in porcine epithelia as observed in human HAE and provide further support for the selection of GP64 as an appropriate envelope pseudotype for future preclinical gene therapy studies in the porcine model of cystic fibrosis (CF).",2012 Nov 27,"['Sinn, Patrick L', 'Cooney, Ashley L', 'Oakland, Mayumi', 'Dylla, Douglas E', 'Wallen, Tanner J', 'Pezzulo, Alejandro A', 'Chang, Eugene H', 'McCray, Paul B']",Mol Ther Nucleic Acids,,,True
9f9f59f3137c9871b1a0d7bfe92b9b9f4087b24b,PMC,Mannosylated Lipid Nano-emulsions Loaded with Lycorine-oleic Acid Ionic Complex for Tumor Cell-specific Delivery,http://dx.doi.org/10.7150/thno.4525,PMC3516834,23227126,CC BY-NC-ND,"This study was to prepare a mannosylated lycorine lipid nano-emulsion formulation (M-LYC-OA-LNEs) for the aim of achieving tumor targeting delivery of lycorine (LYC) . The low lipophilicity of LYC made it hard to be dispersed into lipid nano-emulsions (LNEs). In order to increase its lipophilicity, lycorine-oleic acid ionic complex (LYC-OA) was made. M-LYC-OA-LNEs and uncoated lycorine-oleic acid loaded lipid nano-emulsions (LYC-OA-LNEs) were prepared by solvent injection method and characterized by transmission electron microscopy (TEM), particle size, polydispersity index, zeta-potential and entrapment efficiency analysis. The in vitro cellular uptake and growth inhibition activity studies were performed on A549 cell lines. The entrapment efficiency of M-LYC-OA-LNEs was 82.7 ± 1.6 %. The cellular uptake study showed that coated LNEs were preferably taken up by A549 cells than uncoated LNEs. The effective test by MTT assay showed better growth inhibition activity of M-LYC-OA-LNEs on A549 cell lines when compared with LYC-OA-LNEs and blank LNEs. These results demonstrated that M-LYC-OA-LNEs could be a promising formulation for tumor targeting delivery of LYC with the potential of being applied in the diagnosis and treatment of cancer.",2012 Nov 19,"['Guo, Yangming', 'Liu, Xing', 'Sun, Xun', 'Zhang, Qiang', 'Gong, Tao', 'Zhang, Zhirong']",Theranostics,,,True
6390b0bcdc0ccaa7f754229c217e128901f003f9,PMC,Mannosylated Lipid Nano-emulsions Loaded with Lycorine-oleic Acid Ionic Complex for Tumor Cell-specific Delivery,http://dx.doi.org/10.7150/thno.4525,PMC3516834,23227126,CC BY-NC-ND,"This study was to prepare a mannosylated lycorine lipid nano-emulsion formulation (M-LYC-OA-LNEs) for the aim of achieving tumor targeting delivery of lycorine (LYC) . The low lipophilicity of LYC made it hard to be dispersed into lipid nano-emulsions (LNEs). In order to increase its lipophilicity, lycorine-oleic acid ionic complex (LYC-OA) was made. M-LYC-OA-LNEs and uncoated lycorine-oleic acid loaded lipid nano-emulsions (LYC-OA-LNEs) were prepared by solvent injection method and characterized by transmission electron microscopy (TEM), particle size, polydispersity index, zeta-potential and entrapment efficiency analysis. The in vitro cellular uptake and growth inhibition activity studies were performed on A549 cell lines. The entrapment efficiency of M-LYC-OA-LNEs was 82.7 ± 1.6 %. The cellular uptake study showed that coated LNEs were preferably taken up by A549 cells than uncoated LNEs. The effective test by MTT assay showed better growth inhibition activity of M-LYC-OA-LNEs on A549 cell lines when compared with LYC-OA-LNEs and blank LNEs. These results demonstrated that M-LYC-OA-LNEs could be a promising formulation for tumor targeting delivery of LYC with the potential of being applied in the diagnosis and treatment of cancer.",2012 Nov 19,"['Guo, Yangming', 'Liu, Xing', 'Sun, Xun', 'Zhang, Qiang', 'Gong, Tao', 'Zhang, Zhirong']",Theranostics,,,False
fa0eaef225e1bfa0aa470be4c089ae0689193fec,PMC,Emerging Infectious Diseases in 2012: 20 Years after the Institute of Medicine Report,http://dx.doi.org/10.1128/mBio.00494-12,PMC3520107,23232716,CC BY-NC-SA,"Twenty years ago (1992), a landmark Institute of Medicine report entitled “Emerging Infections: Microbial Threats to Health in the United States” underscored the important but often underappreciated concept of emerging infectious diseases (EIDs). A review of the progress made and setbacks experienced over the past 2 decades suggests that even though many new diseases have emerged, such as SARS (severe acute respiratory syndrome) and the 2009 pandemic influenza, significant advances have occurred in EID control, prevention, and treatment. Among many elements of the increase in the capacity to control EIDs are genomics-associated advances in microbial detection and treatment, improved disease surveillance, and greater awareness of EIDs and the complicated variables that underlie emergence. In looking back over the past 20 years, it is apparent that we are in a time of great change in which both the challenge of EIDs and our responses to them are being transformed. Recent advances support guarded optimism that further breakthroughs lie ahead.",2012 Dec 11,"['Morens, David M.', 'Fauci, Anthony S.']",mBio,,,True
5650690daf962117b9831c42178ffd6a6a969300,PMC,Human Coronavirus EMC Does Not Require the SARS-Coronavirus Receptor and Maintains Broad Replicative Capability in Mammalian Cell Lines,http://dx.doi.org/10.1128/mBio.00515-12,PMC3520110,23232719,CC BY-NC-SA,"A new human coronavirus (hCoV-EMC) has emerged very recently in the Middle East. The clinical presentation resembled that of the severe acute respiratory syndrome (SARS) as encountered during the epidemic in 2002/2003. In both cases, acute renal failure was observed in humans. HCoV-EMC is a member of the same virus genus as SARS-CoV but constitutes a sister species. Here we investigated whether it might utilize angiotensin-converting enzyme 2 (ACE2), the SARS-CoV receptor. Knowledge of the receptor is highly critical because the restriction of the SARS receptor to deep compartments of the human respiratory tract limited the spread of SARS. In baby hamster kidney (BHK) cells, lentiviral transduction of human ACE2 (hACE2) conferred permissiveness and replication for SARS-CoV but not for hCoV-EMC. Monkey and human kidney cells (LLC-MK2, Vero, and 769-P) and swine kidney cells were permissive for both viruses, but only SARS-CoV infection could be blocked by anti-hACE2 antibody and could be neutralized by preincubation of virus with soluble ACE2. Our data show that ACE2 is neither necessary nor sufficient for hCoV-EMC replication. Moreover, hCoV-EMC, but not SARS-CoV, replicated in cell lines from Rousettus, Rhinolophus, Pipistrellus, Myotis, and Carollia bats, representing four major chiropteran families from both suborders. As human CoV normally cannot replicate in bat cells from different families, this suggests that hCoV-EMC might use a receptor molecule that is conserved in bats, pigs, and humans, implicating a low barrier against cross-host transmission.",2012 Dec 11,"['Müller, Marcel A.', 'Raj, V. Stalin', 'Muth, Doreen', 'Meyer, Benjamin', 'Kallies, Stephan', 'Smits, Saskia L.', 'Wollny, Robert', 'Bestebroer, Theo M.', 'Specht, Sabine', 'Suliman, Tasnim', 'Zimmermann, Katrin', 'Binger, Tabea', 'Eckerle, Isabella', 'Tschapka, Marco', 'Zaki, Ali M.', 'Osterhaus, Albert D. M. E.', 'Fouchier, Ron A. M.', 'Haagmans, Bart L.', 'Drosten, Christian']",mBio,,,True
3230a822ceaf337c5137d32e1505878910621991,PMC,Laboratory Detection of Respiratory Viruses by Automated Techniques,http://dx.doi.org/10.2174/1874357901206010151,PMC3522051,23248735,CC BY-NC,"Advances in clinical virology for detecting respiratory viruses have been focused on nucleic acids amplification techniques, which have converted in the reference method for the diagnosis of acute respiratory infections of viral aetiology. Improvements of current commercial molecular assays to reduce hands-on-time rely on two strategies, a stepwise automation (semi-automation) and the complete automation of the whole procedure. Contributions to the former strategy have been the use of automated nucleic acids extractors, multiplex PCR, real-time PCR and/or DNA arrays for detection of amplicons. Commercial fully-automated molecular systems are now available for the detection of respiratory viruses. Some of them could convert in point-of-care methods substituting antigen tests for detection of respiratory syncytial virus and influenza A and B viruses. This article describes laboratory methods for detection of respiratory viruses. A cost-effective and rational diagnostic algorithm is proposed, considering technical aspects of the available assays, infrastructure possibilities of each laboratory and clinic-epidemiologic factors of the infection",2012 Nov 30,"['Pérez-Ruiz, Mercedes', 'Pedrosa-Corral, Irene', 'Sanbonmatsu-Gámez, Sara', 'Navarro-Marí, José-María']",Open Virol J,,,True
68f9d17b3481fc9b2466a48716d7e977ca9bbfad,PMC,Application of Molecular Diagnostic Techniques for Viral Testing,http://dx.doi.org/10.2174/1874357901206010104,PMC3522074,23248732,CC BY-NC,"Nucleic acid amplification techniques are commonly used currently to diagnose viral diseases and manage patients with this kind of illnesses. These techniques have had a rapid but unconventional route of development during the last 30 years, with the discovery and introduction of several assays in clinical diagnosis. The increase in the number of commercially available methods has facilitated the use of this technology in the majority of laboratories worldwide. This technology has reduced the use of some other techniques such as viral culture based methods and serological assays in the clinical virology laboratory. Moreover, nucleic acid amplification techniques are now the methods of reference and also the most useful assays for the diagnosis in several diseases. The introduction of these techniques and their automation provides new opportunities for the clinical laboratory to affect patient care. The main objectives in performing nucleic acid tests in this field are to provide timely results useful for high-quality patient care at a reasonable cost, because rapid results are associated with improvements in patients care. The use of amplification techniques such as polymerase chain reaction, real-time polymerase chain reaction or nucleic acid sequence-based amplification for virus detection, genotyping and quantification have some advantages like high sensitivity and reproducibility, as well as a broad dynamic range. This review is an up-to-date of the main nucleic acid techniques and their clinical applications, and special challenges and opportunities that these techniques currently provide for the clinical virology laboratory.",2012 Nov 30,"Cobo, Fernando",Open Virol J,,,True
0ad29b032fe87db2641893f4cc880c22f2107712,PMC,Preventive Effect of Korean Red Ginseng for Acute Respiratory Illness: A Randomized and Double-Blind Clinical Trial,http://dx.doi.org/10.3346/jkms.2012.27.12.1472,PMC3524425,23255845,CC BY-NC,"Korean Red Ginseng (KRG) is a functional food and has been well known for keeping good health due to its anti-fatigue and immunomodulating activities. However, there is no data on Korean red ginseng for its preventive activity against acute respiratory illness (ARI). The study was conducted in a randomized, double-blinded, placebo-controlled trial in healthy volunteers (Clinical Trial Number: NCT01478009). Our primary efficacy end point was the number of ARI reported and secondary efficacy end point was severity of symptoms, number of symptoms, and duration of ARI. A total of 100 volunteers were enrolled in the study. Fewer subjects in the KRG group reported contracting at least 1 ARI than in the placebo group (12 [24.5%] vs 22 [44.9%], P = 0.034), the difference was statistically significant between the two groups. The symptom duration of the subjects who experienced the ARI, was similar between the two groups (KRG vs placebo; 5.2 ± 2.3 vs 6.3 ± 5.0, P = 0.475). The symptom scores were low tendency in KRG group (KRG vs placebo; 9.5 ± 4.5 vs 17.6 ± 23.1, P = 0.241). The study suggests that KRG may be effective in protecting subjects from contracting ARI, and may have the tendency to decrease the duration and scores of ARI symptoms.",2012 Dec 7,"['Lee, Chang-Seop', 'Lee, Ju-Hyung', 'Oh, Mira', 'Choi, Kyung-Min', 'Jeong, Mi Ran', 'Park, Jong-Dae', 'Kwon, Dae Young', 'Ha, Ki-Chan', 'Park, Eun-Ock', 'Lee, Nuri', 'Kim, Sun-Young', 'Choi, Eun-Kyung', 'Kim, Min-Gul', 'Chae, Soo-Wan']",J Korean Med Sci,,,True
1c202f2c3924d86f516deecda1d47f55d08337da,PMC,Infant Pertussis and Household Transmission in Korea,http://dx.doi.org/10.3346/jkms.2012.27.12.1547,PMC3524436,23255856,CC BY-NC,"A recent resurgence of pertussis has raised public health concerns even in developed countries with high vaccination coverage. The aim of this study was to describe the clinical characteristics of infant pertussis, and to determine the relative importance of household transmission in Korea. The multicenter study was prospectively conducted from January 2009 to September 2011. We identified the demographic and clinical data from these patients and performed the diagnostic tests for pertussis in their household contacts. Twenty-one patients with confirmed pertussis were included in the analysis. All infections occurred in infants younger than 6 months of age (mean age, 2.5 months) who had not completed the primary DTaP vaccination except for one patient. Infants without immunization history had a significant higher lymphocytosis and longer duration of hospital stay compared to those with immunization. All were diagnosed with PCR (100%), however, culture tests showed the lowest sensitivity (42.9%). Presumed source of infection in household contacts was documented in 85.7%, mainly parents (52.6%). Pertussis had a major morbidity in young infants who were not fully immunized. Household members were responsible for pertussis transmission of infants in whom a source could be identified. The control of pertussis through booster vaccination with Tdap in family who is taking care of young infants is necessary in Korea.",2012 Dec 7,"['Kwon, Hyo Jin', 'Yum, Sook Kyung', 'Choi, Ui Yoon', 'Lee, Soo Young', 'Kim, Jong Hyun', 'Kang, Jin Han']",J Korean Med Sci,,,True
365b8f727f890a4833a5ab7ca03d443022e7faf2,PMC,"LoFreq: a sequence-quality aware, ultra-sensitive variant caller for uncovering cell-population heterogeneity from high-throughput sequencing datasets",http://dx.doi.org/10.1093/nar/gks918,PMC3526318,23066108,CC BY-NC,"The study of cell-population heterogeneity in a range of biological systems, from viruses to bacterial isolates to tumor samples, has been transformed by recent advances in sequencing throughput. While the high-coverage afforded can be used, in principle, to identify very rare variants in a population, existing ad hoc approaches frequently fail to distinguish true variants from sequencing errors. We report a method (LoFreq) that models sequencing run-specific error rates to accurately call variants occurring in <0.05% of a population. Using simulated and real datasets (viral, bacterial and human), we show that LoFreq has near-perfect specificity, with significantly improved sensitivity compared with existing methods and can efficiently analyze deep Illumina sequencing datasets without resorting to approximations or heuristics. We also present experimental validation for LoFreq on two different platforms (Fluidigm and Sequenom) and its application to call rare somatic variants from exome sequencing datasets for gastric cancer. Source code and executables for LoFreq are freely available at http://sourceforge.net/projects/lofreq/.",2012 Dec 12,"['Wilm, Andreas', 'Aw, Pauline Poh Kim', 'Bertrand, Denis', 'Yeo, Grace Hui Ting', 'Ong, Swee Hoe', 'Wong, Chang Hua', 'Khor, Chiea Chuen', 'Petric, Rosemary', 'Hibberd, Martin Lloyd', 'Nagarajan, Niranjan']",Nucleic Acids Res,,,True
60b766c8bbe49fb1702f0784263e8a258ed067f3,PMC,The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D),http://dx.doi.org/10.1038/mp.2012.2,PMC3532038,22290120,CC BY-NC-ND,"Given the manifold ways that depression impairs Darwinian fitness, the persistence in the human genome of risk alleles for the disorder remains a much debated mystery. Evolutionary theories that view depressive symptoms as adaptive fail to provide parsimonious explanations for why even mild depressive symptoms impair fitness-relevant social functioning, whereas theories that suggest that depression is maladaptive fail to account for the high prevalence of depression risk alleles in human populations. These limitations warrant novel explanations for the origin and persistence of depression risk alleles. Accordingly, studies on risk alleles for depression were identified using PubMed and Ovid MEDLINE to examine data supporting the hypothesis that risk alleles for depression originated and have been retained in the human genome because these alleles promote pathogen host defense, which includes an integrated suite of immunological and behavioral responses to infection. Depression risk alleles identified by both candidate gene and genome-wide association study (GWAS) methodologies were found to be regularly associated with immune responses to infection that were likely to enhance survival in the ancestral environment. Moreover, data support the role of specific depressive symptoms in pathogen host defense including hyperthermia, reduced bodily iron stores, conservation/withdrawal behavior, hypervigilance and anorexia. By shifting the adaptive context of depression risk alleles from relations with conspecifics to relations with the microbial world, the Pathogen Host Defense (PATHOS-D) hypothesis provides a novel explanation for how depression can be nonadaptive in the social realm, whereas its risk alleles are nonetheless represented at prevalence rates that bespeak an adaptive function.",2013 Jan 31,"['Raison, C L', 'Miller, A H']",Mol Psychiatry,,,True
998472a6428c367f65d047147899c5583db27ea2,PMC,The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D),http://dx.doi.org/10.1038/mp.2012.2,PMC3532038,22290120,CC BY-NC-ND,"Given the manifold ways that depression impairs Darwinian fitness, the persistence in the human genome of risk alleles for the disorder remains a much debated mystery. Evolutionary theories that view depressive symptoms as adaptive fail to provide parsimonious explanations for why even mild depressive symptoms impair fitness-relevant social functioning, whereas theories that suggest that depression is maladaptive fail to account for the high prevalence of depression risk alleles in human populations. These limitations warrant novel explanations for the origin and persistence of depression risk alleles. Accordingly, studies on risk alleles for depression were identified using PubMed and Ovid MEDLINE to examine data supporting the hypothesis that risk alleles for depression originated and have been retained in the human genome because these alleles promote pathogen host defense, which includes an integrated suite of immunological and behavioral responses to infection. Depression risk alleles identified by both candidate gene and genome-wide association study (GWAS) methodologies were found to be regularly associated with immune responses to infection that were likely to enhance survival in the ancestral environment. Moreover, data support the role of specific depressive symptoms in pathogen host defense including hyperthermia, reduced bodily iron stores, conservation/withdrawal behavior, hypervigilance and anorexia. By shifting the adaptive context of depression risk alleles from relations with conspecifics to relations with the microbial world, the Pathogen Host Defense (PATHOS-D) hypothesis provides a novel explanation for how depression can be nonadaptive in the social realm, whereas its risk alleles are nonetheless represented at prevalence rates that bespeak an adaptive function.",2013 Jan 31,"['Raison, C L', 'Miller, A H']",Mol Psychiatry,,,True
e0eb2726170c035bac442479b4bd1909f7af10bb,PMC,The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D),http://dx.doi.org/10.1038/mp.2012.2,PMC3532038,22290120,CC BY-NC-ND,"Given the manifold ways that depression impairs Darwinian fitness, the persistence in the human genome of risk alleles for the disorder remains a much debated mystery. Evolutionary theories that view depressive symptoms as adaptive fail to provide parsimonious explanations for why even mild depressive symptoms impair fitness-relevant social functioning, whereas theories that suggest that depression is maladaptive fail to account for the high prevalence of depression risk alleles in human populations. These limitations warrant novel explanations for the origin and persistence of depression risk alleles. Accordingly, studies on risk alleles for depression were identified using PubMed and Ovid MEDLINE to examine data supporting the hypothesis that risk alleles for depression originated and have been retained in the human genome because these alleles promote pathogen host defense, which includes an integrated suite of immunological and behavioral responses to infection. Depression risk alleles identified by both candidate gene and genome-wide association study (GWAS) methodologies were found to be regularly associated with immune responses to infection that were likely to enhance survival in the ancestral environment. Moreover, data support the role of specific depressive symptoms in pathogen host defense including hyperthermia, reduced bodily iron stores, conservation/withdrawal behavior, hypervigilance and anorexia. By shifting the adaptive context of depression risk alleles from relations with conspecifics to relations with the microbial world, the Pathogen Host Defense (PATHOS-D) hypothesis provides a novel explanation for how depression can be nonadaptive in the social realm, whereas its risk alleles are nonetheless represented at prevalence rates that bespeak an adaptive function.",2013 Jan 31,"['Raison, C L', 'Miller, A H']",Mol Psychiatry,,,False
591779cb69e83083aa7b2d9b031983c802ba2405,PMC,Detection rate and clinical impact of respiratory viruses in children with Kawasaki disease,http://dx.doi.org/10.3345/kjp.2012.55.12.470,PMC3534160,23300502,CC BY-NC,"PURPOSE: The purpose of this prospective case-control study was to survey the detection rate of respiratory viruses in children with Kawasaki disease (KD) by using multiplex reverse transcriptase-polymerase chain reaction (RT-PCR), and to investigate the clinical implications of the prevalence of respiratory viruses during the acute phase of KD. METHODS: RT-PCR assays were carried out to screen for the presence of respiratory syncytial virus A and B, adenovirus, rhinovirus, parainfluenza viruses 1 to 4, influenza virus A and B, metapneumovirus, bocavirus, coronavirus OC43/229E and NL63, and enterovirus in nasopharyngeal secretions of 55 KD patients and 78 control subjects. RESULTS: Virus detection rates in KD patients and control subjects were 32.7% and 30.8%, respectively (P=0.811). However, there was no significant association between the presence of any of the 15 viruses and the incidence of KD. Comparisons between the 18 patients with positive RT-PCR results and the other 37 KD patients revealed no significant differences in terms of clinical findings (including the prevalence of incomplete presentation of the disease) and coronary artery diameter. CONCLUSION: A positive RT-PCR for currently epidemic respiratory viruses should not be used as an evidence against the diagnosis of KD. These viruses were not associated with the incomplete presentation of KD and coronary artery dilatation.",2012 Dec 20,"['Kim, Ja Hye', 'Yu, Jeong Jin', 'Lee, Jina', 'Kim, Mi-Na', 'Ko, Hong Ki', 'Choi, Hyung Soon', 'Kim, Young-Hwue', 'Ko, Jae-Kon']",Korean J Pediatr,,,True
d2192e89ad3965f129fd046a675854c177e5070a,PMC,Early diagnosis of radiodermatitis using lactate dehydrogenase isozymes in hairless mice (SKH1-hr),http://dx.doi.org/10.5625/lar.2012.28.4.239,PMC3542382,23326284,CC BY-NC,"In this study, we evaluate a method for the early diagnosis of radiodermatitis for use in the prevention and therapy of this condition. Hairless mice (SKH1-hr) were used to study the early diagnosis of radiodermatitis. Lactate dehydrogenase (LDH, EC 1.1.1.27) isozymes were analyzed using native-polyacrylamide gel electrophoresis and western blotting of blood serum and tissues collected from SKH1-hr mice. Radiodermatitis developed 24 days after the first X-irradiation. Reduced spleen weight was observed after the last X-irradiation (P<0.05). Thereafter the weight increased until 24 days after the first irradiation, finally reaching levels comparable to those in the sham-irradiated control group. LDH activity was the highest in skeletal muscle and lowest in blood serum. LDH C(4), A(4), A(3)B, A(2)B(2), AB(3), and B(4) isozymes were detected, in the mentioned order, from the cathode. This result was similar in other mouse strains. In the irradiated group, LDH A(4) isozyme levels were reduced in the serum until inflammation occurred, whereas those of B(4) isozyme were elevated. The subunits A and B followed a similar trend to that of LDH A(4) and B(4) isozyme, respectively. Importantly, antibodies against LDH B(4) isozyme could prove useful in the early diagnosis of radiodermatitis.",2012 Dec 26,"['Cho, Sung-Kyu', 'Kim, Won-Dong']",Lab Anim Res,,,True
bb5dbff719709a95c6fbad1d9d4a7f3c3802d23b,PMC,Visitor behaviour and public health implications associated with exotic pet markets: an observational study,http://dx.doi.org/10.1258/shorts.2012.012012,PMC3545344,23323203,CC BY-NC,"OBJECTIVES: To conduct on-site assessments of public health implications at key European pet markets. DESIGN: Observational study of visitor behaviour at stalls that displayed and sold animals, mainly amphibians and reptiles, to assess potential contamination risk from zoonotic pathogens. We noted initial modes of contact as ‘direct’ (handling animals) as well as ‘indirect’ (touching presumed contaminated animal-related sources) and observed whether these visitors subsequently touched their own head or mouth (H1), body (H2) or another person (H3). SETTING: Publicly accessible exotic animal markets in the UK, Germany and Spain. PARTICIPANTS: Anonymous members of the public in a public place. MAIN OUTCOME MEASURES: Occurrence and frequency of public contact (direct, indirect or no contact) with a presumed contaminated source. RESULTS: A total of 813 public visitors were observed as they attended vendors. Of these, 29 (3.6%) made direct contact with an animal and 222 (27.3%) made indirect contact with a presumed contaminated source, with subsequent modes of contact being H1 18.7%, H2 52.2% and H3 9.9%. CONCLUSIONS: Our observations indicate that opportunities for direct and indirect contact at pet markets with presumed contaminated animals and inanimate items constitute a significant and major concern, and that public attendees are exposed to rapid contamination on their person, whether or not these contaminations become associated with any episode of disease involving themselves or others. These public health risks appear unresolvable given the format of the market environment.",2012 Sep 20,"['Warwick, Clifford', 'Arena, Phillip C', 'Steedman, Catrina']",JRSM Short Rep,,,True
372c5fab99bbe7f7862304f94bfaebd3c02f1e1c,PMC,Respiratory Viral Infections after Hematopoietic Stem Cell Transplantation in Children,http://dx.doi.org/10.3346/jkms.2013.28.1.36,PMC3546101,23341709,CC BY-NC,"This study was performed to characterize respiratory viral infections in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Study samples included 402 respiratory specimens obtained from 358 clinical episodes that occurred in the 116 children of the 175 consecutive HSCT cohort at Seoul National University Children's Hospital, Korea from 2007 to 2010. Multiplex reverse-transcription polymerase chain reactions were performed for rhinovirus, respiratory syncytial virus (RSV), parainfluenza viruses (PIVs), adenovirus, human coronavirus (hCoV), influenza viruses and human metapneumovirus. Viruses were identified in 89 clinical episodes that occurred in 58 patients. Among the 89 clinical episodes, frequently detected viruses were rhinovirus in 25 (28.1%), RSV in 23 (25.8%), PIV-3 in 16 (18.0%), adenovirus in 12 (13.5%), and hCoV in 10 (11.2%). Lower respiratory tract infections were diagnosed in 34 (38.2%). Neutropenia was present in 24 (27.0%) episodes and lymphopenia was in 31 (34.8%) episodes. Sixty-three percent of the clinical episodes were hospital-acquired. Three patients died of respiratory failure caused by respiratory viral infections. Respiratory viral infections in pediatric patients who have undergone HSCT are common and are frequently acquired during hospitalization. Continuous monitoring is required to determine the role of respiratory viruses in immunocompromised children and the importance of preventive strategies.",2013 Jan 8,"['Choi, Jae Hong', 'Choi, Eun Hwa', 'Kang, Hyoung Jin', 'Park, Kyung Duk', 'Park, Sung Sup', 'Shin, Hee Young', 'Lee, Hoan Jong', 'Ahn, Hyo Seop']",J Korean Med Sci,,,True
5af9c3bce43b90c81887d5102c0e5c114d40f5dc,PMC,The New Age of Virus Discovery: Genomic Analysis of a Novel Human Betacoronavirus Isolated from a Fatal Case of Pneumonia,http://dx.doi.org/10.1128/mBio.00548-12,PMC3546555,23300251,CC BY-NC-SA,"A new human betacoronavirus in lineage c, tentatively called HCoV-EMC, was isolated from a patient from the Kingdom of Saudi Arabia who died from acute severe pneumonia and renal failure. The viral RNA has been detected in eight additional cases. Sequencing and bioinformatic analysis of the viral genomic RNA showed that it is a novel virus not previously detected in any other species and that its closest relatives are two Asian bat coronaviruses. HCoV-EMC may represent a sporadic spillover to humans from an unknown animal reservoir. In a recent article, van Boheemen et al. demonstrated how state-of-the-art sequencing technology and bioinformatic analysis can quickly provide critical insight into the viral genome sequence, phylogeny, replication strategy, and potential drug and vaccine targets and generate tools to evaluate the possible epidemic risk associated with this novel human virus.",2013 Jan 8,"['Holmes, Kathryn V.', 'Dominguez, Samuel R.']",mBio,,,True
f6b7e95bba8fc989701322484c6318774eb1ed6b,PMC,Observational Research in Childhood Infectious Diseases (ORChID): a dynamic birth cohort study,http://dx.doi.org/10.1136/bmjopen-2012-002134,PMC3547315,23117571,CC BY-NC,"INTRODUCTION: Even in developed economies infectious diseases remain the most common cause of illness in early childhood. Our current understanding of the epidemiology of these infections is limited by reliance on data from decades ago performed using low-sensitivity laboratory methods, and recent studies reporting severe, hospital-managed disease. METHODS AND ANALYSIS: The Observational Research in Childhood Infectious Diseases (ORChID) study is an ongoing study enrolling a dynamic birth cohort to document the community-based epidemiology of viral respiratory and gastrointestinal infections in early childhood. Women are recruited antenatally, and their healthy newborn is followed for the first 2 years of life. Parents keep a daily symptom diary for the study child, collect a weekly anterior nose swab and dirty nappy swab and complete a burden diary when a child meets pre-defined illness criteria. Specimens will be tested for a wide range of viruses by real-time PCR assays. Primary analyses involves calculating incidence rates for acute respiratory illness (ARI) and acute gastroenteritis (AGE) for the cohort by age and seasonality. Control material from children when they are without symptoms will allow us to determine what proportion of ARIs and AGE can be attributed to specific pathogens. Secondary analyses will assess the incidence and shedding duration of specific respiratory and gastrointestinal pathogens. ETHICS AND DISSEMINATION: This study is approved by The Human Research Ethics Committees of the Children's Health Queensland Hospital and Health Service, the Royal Brisbane and Women's Hospital and The University of Queensland. TRIAL REGISTRATION: clinicaltrials.gov NCT01304914.",2012 Oct 31,"['Lambert, Stephen Bernard', 'Ware, Robert S', 'Cook, Anne L', 'Maguire, Frances A', 'Whiley, David M', 'Bialasiewicz, Seweryn', 'Mackay, Ian M', 'Wang, David', 'Sloots, Theo P', 'Nissen, Michael D', 'Grimwood, Keith']",BMJ Open,,,True
fcf83e742399308d0bd2e6c735ec2d46ecb03b9d,PMC,Observational Research in Childhood Infectious Diseases (ORChID): a dynamic birth cohort study,http://dx.doi.org/10.1136/bmjopen-2012-002134,PMC3547315,23117571,CC BY-NC,"INTRODUCTION: Even in developed economies infectious diseases remain the most common cause of illness in early childhood. Our current understanding of the epidemiology of these infections is limited by reliance on data from decades ago performed using low-sensitivity laboratory methods, and recent studies reporting severe, hospital-managed disease. METHODS AND ANALYSIS: The Observational Research in Childhood Infectious Diseases (ORChID) study is an ongoing study enrolling a dynamic birth cohort to document the community-based epidemiology of viral respiratory and gastrointestinal infections in early childhood. Women are recruited antenatally, and their healthy newborn is followed for the first 2 years of life. Parents keep a daily symptom diary for the study child, collect a weekly anterior nose swab and dirty nappy swab and complete a burden diary when a child meets pre-defined illness criteria. Specimens will be tested for a wide range of viruses by real-time PCR assays. Primary analyses involves calculating incidence rates for acute respiratory illness (ARI) and acute gastroenteritis (AGE) for the cohort by age and seasonality. Control material from children when they are without symptoms will allow us to determine what proportion of ARIs and AGE can be attributed to specific pathogens. Secondary analyses will assess the incidence and shedding duration of specific respiratory and gastrointestinal pathogens. ETHICS AND DISSEMINATION: This study is approved by The Human Research Ethics Committees of the Children's Health Queensland Hospital and Health Service, the Royal Brisbane and Women's Hospital and The University of Queensland. TRIAL REGISTRATION: clinicaltrials.gov NCT01304914.",2012 Oct 31,"['Lambert, Stephen Bernard', 'Ware, Robert S', 'Cook, Anne L', 'Maguire, Frances A', 'Whiley, David M', 'Bialasiewicz, Seweryn', 'Mackay, Ian M', 'Wang, David', 'Sloots, Theo P', 'Nissen, Michael D', 'Grimwood, Keith']",BMJ Open,,,True
fc7c462f4b3c1a7e4ab9cf9d7be29353a8595a8c,PMC,Human Coronavirus EMC Is Not the Same as Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/mBio.00002-13,PMC3551544,23322635,CC BY-NC-SA,"A newly identified betacoronavirus, human coronavirus EMC (HCoV-EMC), has been isolated from several patients with respiratory and renal disease in the Middle East. While only a few infected patients have been identified, the mortality of the infection is greater than 50%. Like its better-known cousin severe acute respiratory syndrome coronavirus (SARS-CoV), HCoV-EMC appears to have originated from bats. In a recent article in mBio, Müller et al. described several important differences between the two viruses [M. A. Müller et al., mBio 3(6):e00515-12, 2012, doi:10.1128/mBio.00515-12]. Unlike SARS-CoV, HCoV-EMC can directly infect bat cells. As important, HCoV-EMC does not enter cells using the SARS-CoV receptor, human angiotensin-converting receptor-2 (hACE2). These results provide a strong incentive for identifying the host cell receptor used by HCoV-EMC. Identification of the receptor will provide insight into the pathogenesis of pulmonary and renal disease and may also suggest novel therapeutic interventions.",2013 Jan 15,"['Perlman, Stanley', 'Zhao, Jincun']",mBio,,,True
e1708119ebab348a08e39cff86b1baeda126ce09,PMC,Loss of the abundant nuclear non-coding RNA MALAT1 is compatible with life and development,http://dx.doi.org/10.4161/rna.21089,PMC3551862,22858678,CC BY-NC,"The metastasis-associated lung adenocarcinoma transcript 1, MALAT1, is a long non-coding RNA (lncRNA) that has been discovered as a marker for lung cancer metastasis. It is highly abundant, its expression is strongly regulated in many tumor entities including lung adenocarcinoma and hepatocellular carcinoma as well as physiological processes, and it is associated with many RNA binding proteins and highly conserved throughout evolution. The nuclear transcript MALAT-1 has been functionally associated with gene regulation and alternative splicing and its regulation has been shown to impact proliferation, apoptosis, migration and invasion.   Here, we have developed a human and a mouse knockout system to study the loss-of-function phenotypes of this important ncRNA. In human tumor cells, MALAT1 expression was abrogated using Zinc Finger Nucleases. Unexpectedly, the quantitative loss of MALAT1 did neither affect proliferation nor cell cycle progression nor nuclear architecture in human lung or liver cancer cells. Moreover, genetic loss of Malat1 in a knockout mouse model did not give rise to any obvious phenotype or histological abnormalities in Malat1-null compared with wild-type animals. Thus, loss of the abundant nuclear long ncRNA MALAT1 is compatible with cell viability and normal development.",2012 Aug 1,"['Eißmann, Moritz', 'Gutschner, Tony', 'Hämmerle, Monika', 'Günther, Stefan', 'Caudron-Herger, Maïwen', 'Groß, Matthias', 'Schirmacher, Peter', 'Rippe, Karsten', 'Braun, Thomas', 'Diederichs, Sven', 'Zörnig, Martin']",RNA Biol,,,True
1f7394c2575f1eb1a196c9f19cd4b57ddd05789b,PMC,Quantifying Pathogen Surveillance Using Temporal Genomic Data,http://dx.doi.org/10.1128/mBio.00524-12,PMC3560527,23362319,CC BY-NC-SA,"With the advent of deep sequencing, genomic surveillance has become a popular method for detection of infectious disease, supplementing information gathered by classic clinical or serological techniques to identify host-determinant markers and trace the origin of transmission. However, two main factors complicate genomic surveillance. First, pathogens exhibiting high genetic diversity demand higher levels of scrutiny to obtain an accurate representation of the entire population. Second, current systems of detection are nonuniform, with significant gaps in certain geographic locations and animal reservoirs. Despite past unforeseen pandemics like the 2009 swine-origin H1N1 influenza virus, there is no standardized way of evaluating surveillance. A more complete surveillance system should capture a greater proportion of pathogen diversity. Here we present a novel quantitative method of assessing the completeness of genomic surveillance that incorporates the time of sequence collection, as well as the pathogen’s evolutionary rate. We propose the q2 coefficient, which measures the proportion of sequenced isolates whose closest neighbor in the past is within a genetic distance equivalent to 2 years of evolution, roughly the median time of changing strain selection for influenza A vaccines. Easily interpretable and significantly faster than other methods, the q2 coefficient requires no full phylogenetic characterization or use of arbitrary clade definitions. Application of the q2 coefficient to influenza A virus confirmed poor sampling of swine and avian populations and identified regions with deficient surveillance. We demonstrate that the q2 coefficient can not only be applied to other pathogens, including dengue and West Nile viruses, but also used to describe surveillance dynamics, particularly the effects of different public health policies.",2013 Jan 29,"['Chan, Joseph M.', 'Rabadan, Raul']",mBio,,,True
69576ba6661007a4795bde815a55f309a5554803,PMC,Quantifying Pathogen Surveillance Using Temporal Genomic Data,http://dx.doi.org/10.1128/mBio.00524-12,PMC3560527,23362319,CC BY-NC-SA,"With the advent of deep sequencing, genomic surveillance has become a popular method for detection of infectious disease, supplementing information gathered by classic clinical or serological techniques to identify host-determinant markers and trace the origin of transmission. However, two main factors complicate genomic surveillance. First, pathogens exhibiting high genetic diversity demand higher levels of scrutiny to obtain an accurate representation of the entire population. Second, current systems of detection are nonuniform, with significant gaps in certain geographic locations and animal reservoirs. Despite past unforeseen pandemics like the 2009 swine-origin H1N1 influenza virus, there is no standardized way of evaluating surveillance. A more complete surveillance system should capture a greater proportion of pathogen diversity. Here we present a novel quantitative method of assessing the completeness of genomic surveillance that incorporates the time of sequence collection, as well as the pathogen’s evolutionary rate. We propose the q2 coefficient, which measures the proportion of sequenced isolates whose closest neighbor in the past is within a genetic distance equivalent to 2 years of evolution, roughly the median time of changing strain selection for influenza A vaccines. Easily interpretable and significantly faster than other methods, the q2 coefficient requires no full phylogenetic characterization or use of arbitrary clade definitions. Application of the q2 coefficient to influenza A virus confirmed poor sampling of swine and avian populations and identified regions with deficient surveillance. We demonstrate that the q2 coefficient can not only be applied to other pathogens, including dengue and West Nile viruses, but also used to describe surveillance dynamics, particularly the effects of different public health policies.",2013 Jan 29,"['Chan, Joseph M.', 'Rabadan, Raul']",mBio,,,False
27296b63b832074088c09c99f64acb0ce8d12f40,PMC,Quantifying Pathogen Surveillance Using Temporal Genomic Data,http://dx.doi.org/10.1128/mBio.00524-12,PMC3560527,23362319,CC BY-NC-SA,"With the advent of deep sequencing, genomic surveillance has become a popular method for detection of infectious disease, supplementing information gathered by classic clinical or serological techniques to identify host-determinant markers and trace the origin of transmission. However, two main factors complicate genomic surveillance. First, pathogens exhibiting high genetic diversity demand higher levels of scrutiny to obtain an accurate representation of the entire population. Second, current systems of detection are nonuniform, with significant gaps in certain geographic locations and animal reservoirs. Despite past unforeseen pandemics like the 2009 swine-origin H1N1 influenza virus, there is no standardized way of evaluating surveillance. A more complete surveillance system should capture a greater proportion of pathogen diversity. Here we present a novel quantitative method of assessing the completeness of genomic surveillance that incorporates the time of sequence collection, as well as the pathogen’s evolutionary rate. We propose the q2 coefficient, which measures the proportion of sequenced isolates whose closest neighbor in the past is within a genetic distance equivalent to 2 years of evolution, roughly the median time of changing strain selection for influenza A vaccines. Easily interpretable and significantly faster than other methods, the q2 coefficient requires no full phylogenetic characterization or use of arbitrary clade definitions. Application of the q2 coefficient to influenza A virus confirmed poor sampling of swine and avian populations and identified regions with deficient surveillance. We demonstrate that the q2 coefficient can not only be applied to other pathogens, including dengue and West Nile viruses, but also used to describe surveillance dynamics, particularly the effects of different public health policies.",2013 Jan 29,"['Chan, Joseph M.', 'Rabadan, Raul']",mBio,,,False
6f16c97451b1e2462c64e57061b441aae5885a52,PMC,Quantifying Pathogen Surveillance Using Temporal Genomic Data,http://dx.doi.org/10.1128/mBio.00524-12,PMC3560527,23362319,CC BY-NC-SA,"With the advent of deep sequencing, genomic surveillance has become a popular method for detection of infectious disease, supplementing information gathered by classic clinical or serological techniques to identify host-determinant markers and trace the origin of transmission. However, two main factors complicate genomic surveillance. First, pathogens exhibiting high genetic diversity demand higher levels of scrutiny to obtain an accurate representation of the entire population. Second, current systems of detection are nonuniform, with significant gaps in certain geographic locations and animal reservoirs. Despite past unforeseen pandemics like the 2009 swine-origin H1N1 influenza virus, there is no standardized way of evaluating surveillance. A more complete surveillance system should capture a greater proportion of pathogen diversity. Here we present a novel quantitative method of assessing the completeness of genomic surveillance that incorporates the time of sequence collection, as well as the pathogen’s evolutionary rate. We propose the q2 coefficient, which measures the proportion of sequenced isolates whose closest neighbor in the past is within a genetic distance equivalent to 2 years of evolution, roughly the median time of changing strain selection for influenza A vaccines. Easily interpretable and significantly faster than other methods, the q2 coefficient requires no full phylogenetic characterization or use of arbitrary clade definitions. Application of the q2 coefficient to influenza A virus confirmed poor sampling of swine and avian populations and identified regions with deficient surveillance. We demonstrate that the q2 coefficient can not only be applied to other pathogens, including dengue and West Nile viruses, but also used to describe surveillance dynamics, particularly the effects of different public health policies.",2013 Jan 29,"['Chan, Joseph M.', 'Rabadan, Raul']",mBio,,,False
e1f247d3a998a0ae0a1f3c43f7c541a1c7084ee3,PMC,Quantifying Pathogen Surveillance Using Temporal Genomic Data,http://dx.doi.org/10.1128/mBio.00524-12,PMC3560527,23362319,CC BY-NC-SA,"With the advent of deep sequencing, genomic surveillance has become a popular method for detection of infectious disease, supplementing information gathered by classic clinical or serological techniques to identify host-determinant markers and trace the origin of transmission. However, two main factors complicate genomic surveillance. First, pathogens exhibiting high genetic diversity demand higher levels of scrutiny to obtain an accurate representation of the entire population. Second, current systems of detection are nonuniform, with significant gaps in certain geographic locations and animal reservoirs. Despite past unforeseen pandemics like the 2009 swine-origin H1N1 influenza virus, there is no standardized way of evaluating surveillance. A more complete surveillance system should capture a greater proportion of pathogen diversity. Here we present a novel quantitative method of assessing the completeness of genomic surveillance that incorporates the time of sequence collection, as well as the pathogen’s evolutionary rate. We propose the q2 coefficient, which measures the proportion of sequenced isolates whose closest neighbor in the past is within a genetic distance equivalent to 2 years of evolution, roughly the median time of changing strain selection for influenza A vaccines. Easily interpretable and significantly faster than other methods, the q2 coefficient requires no full phylogenetic characterization or use of arbitrary clade definitions. Application of the q2 coefficient to influenza A virus confirmed poor sampling of swine and avian populations and identified regions with deficient surveillance. We demonstrate that the q2 coefficient can not only be applied to other pathogens, including dengue and West Nile viruses, but also used to describe surveillance dynamics, particularly the effects of different public health policies.",2013 Jan 29,"['Chan, Joseph M.', 'Rabadan, Raul']",mBio,,,False
97a1bf0cca7e6b48364be99814a22a5440c521f3,PMC,Next-Generation Sequencing of Small RNAs from HIV-Infected Cells Identifies Phased microRNA Expression Patterns and Candidate Novel microRNAs Differentially Expressed upon Infection,http://dx.doi.org/10.1128/mBio.00549-12,PMC3560529,23386435,CC BY-NC-SA,"HIV infection of CD4(+) T cells induces a range of host transcriptional changes in mRNAs as well as microRNAs that may coordinate changes in mRNAs. To survey these dynamic changes, we applied next-generation sequencing, analyzing the small RNA fraction of HIV-infected cells at 5, 12, and 24 h postinfection (RNA-Seq). These time points afforded a view of the transcriptomic changes occurring both before and during viral replication. In the resulting small RNA-Seq data set, we detected a phased pattern of microRNA expression. Largely distinct sets of microRNAs were found to be suppressed at 5 and 12 h postinfection, and both sets of changes rebounded later in infection. A larger set of microRNA changes was observed at 24 h postinfection. When integrated with mRNA expression data, the small RNA-Seq data indicated a role for microRNAs in transcriptional regulation, T cell activation, and cell cycle during HIV infection. As a unique benefit of next-generation sequencing, we also detected candidate novel host microRNAs differentially expressed during infection, including one whose downregulation at 24 h postinfection may allow full replication of HIV to proceed. Collectively, our data provide a uniquely comprehensive view of the changes in host microRNAs induced by HIV during cellular infection.",2013 Feb 5,"['Chang, Stewart T.', 'Thomas, Matthew J.', 'Sova, Pavel', 'Green, Richard R.', 'Palermo, Robert E.', 'Katze, Michael G.']",mBio,,,True
8dc8c40ee8b61c5660b15c9e81e928eb3dc44ee5,PMC,Highly similar structural frames link the template tunnel and NTP entry tunnel to the exterior surface in RNA-dependent RNA polymerases,http://dx.doi.org/10.1093/nar/gks1251,PMC3561941,23275546,CC BY-NC,"RNA-dependent RNA polymerase (RdRp) is essential to viral replication and is therefore one of the primary targets of countermeasures against these dangerous infectious agents. Development of broad-spectrum therapeutics targeting polymerases has been hampered by the extreme sequence variability of these sequences. RdRps range in length from 400–800 residues, yet contain only ∼20 residues that are conserved in most species. In this study, we made structure-based comparisons that are independent of sequence composition using a recently developed algorithm. We identified residue-to-residue correspondences of multiple protein structures and created (two-dimensional) structure-based alignment maps of 37 polymerase structures that provide both sequence and structure details. Using these maps, we determined that ∼75% of each polymerase species consists of seven protein segments, each of which has high structural similarity to segments in other species, though they are widely divergent in sequence composition and order. We define each of these segments as a ‘homomorph’, and each includes (though most are much larger than) the well-known conserved polymerase motifs. All homomorphs contact the template tunnel or nucleoside triphosphate (NTP) entry tunnel and the exterior of the protein, suggesting they constitute a structural and functional skeleton common among the polymerases.",2013 Feb 25,"['Lang, Dorothy M.', 'Zemla, A. T.', 'Zhou, C. L. Ecale']",Nucleic Acids Res,,,True
dd32b30f23c6d0063de22dc6196494d92264668a,PMC,Highly similar structural frames link the template tunnel and NTP entry tunnel to the exterior surface in RNA-dependent RNA polymerases,http://dx.doi.org/10.1093/nar/gks1251,PMC3561941,23275546,CC BY-NC,"RNA-dependent RNA polymerase (RdRp) is essential to viral replication and is therefore one of the primary targets of countermeasures against these dangerous infectious agents. Development of broad-spectrum therapeutics targeting polymerases has been hampered by the extreme sequence variability of these sequences. RdRps range in length from 400–800 residues, yet contain only ∼20 residues that are conserved in most species. In this study, we made structure-based comparisons that are independent of sequence composition using a recently developed algorithm. We identified residue-to-residue correspondences of multiple protein structures and created (two-dimensional) structure-based alignment maps of 37 polymerase structures that provide both sequence and structure details. Using these maps, we determined that ∼75% of each polymerase species consists of seven protein segments, each of which has high structural similarity to segments in other species, though they are widely divergent in sequence composition and order. We define each of these segments as a ‘homomorph’, and each includes (though most are much larger than) the well-known conserved polymerase motifs. All homomorphs contact the template tunnel or nucleoside triphosphate (NTP) entry tunnel and the exterior of the protein, suggesting they constitute a structural and functional skeleton common among the polymerases.",2013 Feb 25,"['Lang, Dorothy M.', 'Zemla, A. T.', 'Zhou, C. L. Ecale']",Nucleic Acids Res,,,False
21bf43af5e28e560db8ea6f8cf62c6df557d48d7,PMC,Highly similar structural frames link the template tunnel and NTP entry tunnel to the exterior surface in RNA-dependent RNA polymerases,http://dx.doi.org/10.1093/nar/gks1251,PMC3561941,23275546,CC BY-NC,"RNA-dependent RNA polymerase (RdRp) is essential to viral replication and is therefore one of the primary targets of countermeasures against these dangerous infectious agents. Development of broad-spectrum therapeutics targeting polymerases has been hampered by the extreme sequence variability of these sequences. RdRps range in length from 400–800 residues, yet contain only ∼20 residues that are conserved in most species. In this study, we made structure-based comparisons that are independent of sequence composition using a recently developed algorithm. We identified residue-to-residue correspondences of multiple protein structures and created (two-dimensional) structure-based alignment maps of 37 polymerase structures that provide both sequence and structure details. Using these maps, we determined that ∼75% of each polymerase species consists of seven protein segments, each of which has high structural similarity to segments in other species, though they are widely divergent in sequence composition and order. We define each of these segments as a ‘homomorph’, and each includes (though most are much larger than) the well-known conserved polymerase motifs. All homomorphs contact the template tunnel or nucleoside triphosphate (NTP) entry tunnel and the exterior of the protein, suggesting they constitute a structural and functional skeleton common among the polymerases.",2013 Feb 25,"['Lang, Dorothy M.', 'Zemla, A. T.', 'Zhou, C. L. Ecale']",Nucleic Acids Res,,,False
c2ad458ccf62686e340e51ea95c439e7c4e2bc29,PMC,HIV-1 frameshift efficiency is primarily determined by the stability of base pairs positioned at the mRNA entrance channel of the ribosome,http://dx.doi.org/10.1093/nar/gks1254,PMC3561942,23248007,CC BY-NC,"The human immunodeficiency virus (HIV) requires a programmed −1 ribosomal frameshift for Pol gene expression. The HIV frameshift site consists of a heptanucleotide slippery sequence (UUUUUUA) followed by a spacer region and a downstream RNA stem–loop structure. Here we investigate the role of the RNA structure in promoting the −1 frameshift. The stem–loop was systematically altered to decouple the contributions of local and overall thermodynamic stability towards frameshift efficiency. No correlation between overall stability and frameshift efficiency is observed. In contrast, there is a strong correlation between frameshift efficiency and the local thermodynamic stability of the first 3–4 bp in the stem–loop, which are predicted to reside at the opening of the mRNA entrance channel when the ribosome is paused at the slippery site. Insertion or deletions in the spacer region appear to correspondingly change the identity of the base pairs encountered 8 nt downstream of the slippery site. Finally, the role of the surrounding genomic secondary structure was investigated and found to have a modest impact on frameshift efficiency, consistent with the hypothesis that the genomic secondary structure attenuates frameshifting by affecting the overall rate of translation.",2013 Feb 15,"['Mouzakis, Kathryn D.', 'Lang, Andrew L.', 'Vander Meulen, Kirk A.', 'Easterday, Preston D.', 'Butcher, Samuel E.']",Nucleic Acids Res,,,True
b8aa79f46c33116f3c3acc5ff61ee601507c56b8,PMC,HIV-1 frameshift efficiency is primarily determined by the stability of base pairs positioned at the mRNA entrance channel of the ribosome,http://dx.doi.org/10.1093/nar/gks1254,PMC3561942,23248007,CC BY-NC,"The human immunodeficiency virus (HIV) requires a programmed −1 ribosomal frameshift for Pol gene expression. The HIV frameshift site consists of a heptanucleotide slippery sequence (UUUUUUA) followed by a spacer region and a downstream RNA stem–loop structure. Here we investigate the role of the RNA structure in promoting the −1 frameshift. The stem–loop was systematically altered to decouple the contributions of local and overall thermodynamic stability towards frameshift efficiency. No correlation between overall stability and frameshift efficiency is observed. In contrast, there is a strong correlation between frameshift efficiency and the local thermodynamic stability of the first 3–4 bp in the stem–loop, which are predicted to reside at the opening of the mRNA entrance channel when the ribosome is paused at the slippery site. Insertion or deletions in the spacer region appear to correspondingly change the identity of the base pairs encountered 8 nt downstream of the slippery site. Finally, the role of the surrounding genomic secondary structure was investigated and found to have a modest impact on frameshift efficiency, consistent with the hypothesis that the genomic secondary structure attenuates frameshifting by affecting the overall rate of translation.",2013 Feb 15,"['Mouzakis, Kathryn D.', 'Lang, Andrew L.', 'Vander Meulen, Kirk A.', 'Easterday, Preston D.', 'Butcher, Samuel E.']",Nucleic Acids Res,,,False
d2685fbd92927824244e9d90a145f59f44317db0,PMC,Interferon-induced transmembrane protein-3 genetic variant rs12252-C is associated with severe influenza in Chinese individuals,http://dx.doi.org/10.1038/ncomms2433,PMC3562464,23361009,CC BY-NC-SA,"The SNP rs12252-C allele alters the function of interferon-induced transmembrane protein-3 increasing the disease severity of influenza virus infection in Caucasians, but the allele is rare. However, rs12252-C is much more common in Han Chinese. Here we report that the CC genotype is found in 69% of Chinese patients with severe pandemic influenza A H1N1/09 virus infection compared with 25% in those with mild infection. Specifically, the CC genotype was estimated to confer a sixfold greater risk for severe infection than the CT and TT genotypes. More importantly, because the risk genotype occurs with such a high frequency, its effect translates to a large population-attributable risk of 54.3% for severe infection in the Chinese population studied compared with 5.4% in Northern Europeans. Interferon-induced transmembrane protein-3 genetic variants could, therefore, have a strong effect of the epidemiology of influenza in China and in people of Chinese descent.",2013 Jan 29,"['Zhang, Yong-Hong', 'Zhao, Yan', 'Li, Ning', 'Peng, Yan-Chun', 'Giannoulatou, Eleni', 'Jin, Rong-Hua', 'Yan, Hui-Ping', 'Wu, Hao', 'Liu, Jin-Hua', 'Liu, Ning', 'Wang, Da-Yan', 'Shu, Yue-Long', 'Ho, Ling-Pei', 'Kellam, Paul', 'McMichael, Andrew', 'Dong, Tao']",Nat Commun,,,True
3f9572ae671d876279b4d2cd6b6544b24fb3e52d,PMC,Cystatins in Immune System,http://dx.doi.org/10.7150/jca.5044,PMC3564246,23386904,CC BY-NC-ND,"Cystatins comprise a large superfamily of related proteins with diverse biological activities. They were initially characterised as inhibitors of lysosomal cysteine proteases, however, in recent years some alternative functions for cystatins have been proposed. Cystatins possessing inhibitory function are members of three families, family I (stefins), family II (cystatins) and family III (kininogens). Stefin A is often linked to neoplastic changes in epithelium while another family I cystatin, stefin B is supposed to have a specific role in neuredegenerative diseases. Cystatin C, a typical type II cystatin, is expressed in a variety of human tissues and cells. On the other hand, expression of other type II cystatins is more specific. Cystatin F is an endo/lysosome targeted protease inhibitor, selectively expressed in immune cells, suggesting its role in processes related to immune response. Our recent work points on its role in regulation of dendritic cell maturation and in natural killer cells functional inactivation that may enhance tumor survival. Cystatin E/M expression is mainly restricted to the epithelia of the skin which emphasizes its prominent role in cutaneous biology. Here, we review the current knowledge on type I (stefins A and B) and type II cystatins (cystatins C, F and E/M) in pathologies, with particular emphasis on their suppressive vs. promotional function in the tumorigenesis and metastasis. We proposed that an imbalance between cathepsins and cystatins may attenuate immune cell functions and facilitate tumor cell invasion.",2012 Dec 20,"['Magister, Špela', 'Kos, Janko']",J Cancer,,,True
7377d7ad2d731e3fbd3ed4fa15ed541b06e3587c,PMC,Fulminant hemophagocytic lymphohistiocytosis secondary to a reactivated EBV infection: A case report,http://dx.doi.org/10.3109/03009734.2012.744122,PMC3572670,23398237,CC BY-NC,"Hemophagocytic lymphohistiocytosis (HLH) is an aggressive inflammatory syndrome that results from inappropriate activation of the immune system. HLH has a high mortality if not treated. We describe a case of a fulminant HLH, associated with a reactivation of an EBV infection. The patient responded well to steroid treatment.",2013 Mar 13,"['Antonodimitrakis, Pantelis', 'Wassberg, Cecilia', 'Gerovasileiou, Spyridon', 'Back, Johan', 'Hällgren, Roger', 'Olsen, Björn']",Ups J Med Sci,,,True
da700649fef6382fec2ae238b91ffdbbc0e2c301,PMC,Efficient Replication of the Novel Human Betacoronavirus EMC on Primary Human Epithelium Highlights Its Zoonotic Potential,http://dx.doi.org/10.1128/mBio.00611-12,PMC3573664,23422412,CC BY-NC-SA,"The recent emergence of a novel human coronavirus (HCoV-EMC) in the Middle East raised considerable concerns, as it is associated with severe acute pneumonia, renal failure, and fatal outcome and thus resembles the clinical presentation of severe acute respiratory syndrome (SARS) observed in 2002 and 2003. Like SARS-CoV, HCoV-EMC is of zoonotic origin and closely related to bat coronaviruses. The human airway epithelium (HAE) represents the entry point and primary target tissue for respiratory viruses and is highly relevant for assessing the zoonotic potential of emerging respiratory viruses, such as HCoV-EMC. Here, we show that pseudostratified HAE cultures derived from different donors are highly permissive to HCoV-EMC infection, and by using reverse transcription (RT)-PCR and RNAseq data, we experimentally determined the identity of seven HCoV-EMC subgenomic mRNAs. Although the HAE cells were readily responsive to type I and type III interferon (IFN), we observed neither a pronounced inflammatory cytokine nor any detectable IFN responses following HCoV-EMC, SARS-CoV, or HCoV-229E infection, suggesting that innate immune evasion mechanisms and putative IFN antagonists of HCoV-EMC are operational in the new host. Importantly, however, we demonstrate that both type I and type III IFN can efficiently reduce HCoV-EMC replication in HAE cultures, providing a possible treatment option in cases of suspected HCoV-EMC infection.",2013 Feb 19,"['Kindler, Eveline', 'Jónsdóttir, Hulda R.', 'Muth, Doreen', 'Hamming, Ole J.', 'Hartmann, Rune', 'Rodriguez, Regulo', 'Geffers, Robert', 'Fouchier, Ron A. M.', 'Drosten, Christian', 'Müller, Marcel A.', 'Dijkman, Ronald', 'Thiel, Volker']",mBio,,,True
fa021bfcf95acdbde556098bfd84e8a84c7948c9,PMC,RNA dimerization plays a role in ribosomal frameshifting of the SARS coronavirus,http://dx.doi.org/10.1093/nar/gks1361,PMC3575852,23275571,CC BY-NC,"Messenger RNA encoded signals that are involved in programmed -1 ribosomal frameshifting (-1 PRF) are typically two-stemmed hairpin (H)-type pseudoknots (pks). We previously described an unusual three-stemmed pseudoknot from the severe acute respiratory syndrome (SARS) coronavirus (CoV) that stimulated -1 PRF. The conserved existence of a third stem–loop suggested an important hitherto unknown function. Here we present new information describing structure and function of the third stem of the SARS pseudoknot. We uncovered RNA dimerization through a palindromic sequence embedded in the SARS-CoV Stem 3. Further in vitro analysis revealed that SARS-CoV RNA dimers assemble through ‘kissing’ loop–loop interactions. We also show that loop–loop kissing complex formation becomes more efficient at physiological temperature and in the presence of magnesium. When the palindromic sequence was mutated, in vitro RNA dimerization was abolished, and frameshifting was reduced from 15 to 5.7%. Furthermore, the inability to dimerize caused by the silent codon change in Stem 3 of SARS-CoV changed the viral growth kinetics and affected the levels of genomic and subgenomic RNA in infected cells. These results suggest that the homodimeric RNA complex formed by the SARS pseudoknot occurs in the cellular environment and that loop–loop kissing interactions involving Stem 3 modulate -1 PRF and play a role in subgenomic and full-length RNA synthesis.",2013 Feb 26,"['Ishimaru, Daniella', 'Plant, Ewan P.', 'Sims, Amy C.', 'Yount, Boyd L.', 'Roth, Braden M.', 'Eldho, Nadukkudy V.', 'Pérez-Alvarado, Gabriela C.', 'Armbruster, David W.', 'Baric, Ralph S.', 'Dinman, Jonathan D.', 'Taylor, Deborah R.', 'Hennig, Mirko']",Nucleic Acids Res,,,True
ac68aa8c2dcbf6afb55b8ef2dccb0f41cf590d2a,PMC,RNA dimerization plays a role in ribosomal frameshifting of the SARS coronavirus,http://dx.doi.org/10.1093/nar/gks1361,PMC3575852,23275571,CC BY-NC,"Messenger RNA encoded signals that are involved in programmed -1 ribosomal frameshifting (-1 PRF) are typically two-stemmed hairpin (H)-type pseudoknots (pks). We previously described an unusual three-stemmed pseudoknot from the severe acute respiratory syndrome (SARS) coronavirus (CoV) that stimulated -1 PRF. The conserved existence of a third stem–loop suggested an important hitherto unknown function. Here we present new information describing structure and function of the third stem of the SARS pseudoknot. We uncovered RNA dimerization through a palindromic sequence embedded in the SARS-CoV Stem 3. Further in vitro analysis revealed that SARS-CoV RNA dimers assemble through ‘kissing’ loop–loop interactions. We also show that loop–loop kissing complex formation becomes more efficient at physiological temperature and in the presence of magnesium. When the palindromic sequence was mutated, in vitro RNA dimerization was abolished, and frameshifting was reduced from 15 to 5.7%. Furthermore, the inability to dimerize caused by the silent codon change in Stem 3 of SARS-CoV changed the viral growth kinetics and affected the levels of genomic and subgenomic RNA in infected cells. These results suggest that the homodimeric RNA complex formed by the SARS pseudoknot occurs in the cellular environment and that loop–loop kissing interactions involving Stem 3 modulate -1 PRF and play a role in subgenomic and full-length RNA synthesis.",2013 Feb 26,"['Ishimaru, Daniella', 'Plant, Ewan P.', 'Sims, Amy C.', 'Yount, Boyd L.', 'Roth, Braden M.', 'Eldho, Nadukkudy V.', 'Pérez-Alvarado, Gabriela C.', 'Armbruster, David W.', 'Baric, Ralph S.', 'Dinman, Jonathan D.', 'Taylor, Deborah R.', 'Hennig, Mirko']",Nucleic Acids Res,,,False
b16173612f53649fbd4db78654874bee5d4d607f,PMC,An independent endocytic pathway stimulates different monocyte subsets by the a2 N-terminus domain of vacuolar-ATPase,http://dx.doi.org/10.4161/onci.22978,PMC3583941,23483532,CC BY-NC,"The vacuolar ATPase (V-ATPase) plays an important role in tumor progression and metastases. A novel peptide from the a2 isoform of V-ATPase called a2NTD has been shown to exert an immunoregulatory role in the tumor microenvironment by controlling the maturation of monocytes toward a tumor-associated macrophage phenotype. Our data indicate that a2NTD binds to the surface of monocytes. a2NTD was preferentially endocytosed by pro-inflammatory monocytes bearing a CD14(++)CD16(+) phenotype, which is associated with the monocyte-to-macrophage maturation process. Both a2NTD binding and internalization led to production of the pro-inflammatory cytokines interleukin (IL)-1α and IL-1β by CD14(++)CD16(-) (classical) and CD14(++)CD16(+ )(intermediate) monocytes. a2NTD was internalized via a macropinocytosis mechanism utilizing scavenger receptors. However, the inhibition of a2NTD endocytosis did not reduce cytokine production by monocytes. This points to the existence of two receptors that respond to a2NTD: scavengers receptors that mediate cellular uptake and an hitherto unidentified receptor stimulating the production of inflammatory cytokines. Both of these monocyte receptors may be important in generating the localized inflammation that is often required to promote tumor growth and hence may constitute novel targets for the development of anticancer drugs.",2013 Jan 1,"['Kwong, Christina', 'Gilman-Sachs, Alice', 'Beaman, Kenneth']",Oncoimmunology,,,True
6c27fa7acef9cb98b3e5eb0567277c8054a2d534,PMC,An independent endocytic pathway stimulates different monocyte subsets by the a2 N-terminus domain of vacuolar-ATPase,http://dx.doi.org/10.4161/onci.22978,PMC3583941,23483532,CC BY-NC,"The vacuolar ATPase (V-ATPase) plays an important role in tumor progression and metastases. A novel peptide from the a2 isoform of V-ATPase called a2NTD has been shown to exert an immunoregulatory role in the tumor microenvironment by controlling the maturation of monocytes toward a tumor-associated macrophage phenotype. Our data indicate that a2NTD binds to the surface of monocytes. a2NTD was preferentially endocytosed by pro-inflammatory monocytes bearing a CD14(++)CD16(+) phenotype, which is associated with the monocyte-to-macrophage maturation process. Both a2NTD binding and internalization led to production of the pro-inflammatory cytokines interleukin (IL)-1α and IL-1β by CD14(++)CD16(-) (classical) and CD14(++)CD16(+ )(intermediate) monocytes. a2NTD was internalized via a macropinocytosis mechanism utilizing scavenger receptors. However, the inhibition of a2NTD endocytosis did not reduce cytokine production by monocytes. This points to the existence of two receptors that respond to a2NTD: scavengers receptors that mediate cellular uptake and an hitherto unidentified receptor stimulating the production of inflammatory cytokines. Both of these monocyte receptors may be important in generating the localized inflammation that is often required to promote tumor growth and hence may constitute novel targets for the development of anticancer drugs.",2013 Jan 1,"['Kwong, Christina', 'Gilman-Sachs, Alice', 'Beaman, Kenneth']",Oncoimmunology,,,False
4ea10ee40e0ecf02db0667f87ed9ee4e2bd6aa9c,PMC,Anti-radiation damage effect of polyethylenimine as a toll-like receptor 5 targeted agonist,http://dx.doi.org/10.1093/jrr/rrs098,PMC3589936,23104900,CC BY-NC,"A number of agents are now available for use in protecting against ionizing radiation. These radiation-protective agents, however, have many adverse effects. Efforts have been made to develop new radiation-protective agents for medical application. Here, we investigated whether a compound, polyethylenimine (PEI), which activates Toll-like receptor 5 (TLR5)-mediated NF-kB signaling pathways, could have an anti-radiation effect on a mouse model. First, a cell-based screening model for an agonist of TLR5-mediated NF-kB pathway was established and then validated by activation of TLR5-mediated NF-kB luciferase reporter activity with a known TLR5 agonist, flagellin. We found that PEI induced dose-dependent activation of the TLR5-mediated NF-kB pathway, indicating that PEI is indeed a TLR5 agonist. Furthermore, the anti-radiation effect of polyethylenimine was assessed using a γ-ray total body irradiation (TBI) mouse model. Compared with the irradiation control, both survival time and survival rate were significantly improved in mice that received either a low dose of polyethylenimine (P= 0.019) or a high dose of polyethylenimine (P< 0.001). We also observed a positive correlation between animal body weight and survival time in mice that received a low dose of polyethylenimine, a high dose of polyethylenimine and amifostine, over a period of 30 days, r= 0.42 (P< 0.02), 0.72 (P< 0.0001) and 0.95 (P< 0.0001), respectively, while a negative correlation between animal body weight and survival time was observed in the irradiation control (r= –0.89; P< 0.0001). These results indicate that polyethylenimine is a new TLR5 agonist with potential application in offering protection for patients receiving radiotherapy or in radiation-related accidents.",2013 Mar 26,"['Hu, Zhiqiang', 'Xing, Yaling', 'Qian, Yuanyu', 'Chen, Xiaojuan', 'Tu, Jian', 'Ren, Lening', 'Wang, Kai', 'Chen, Zhongbin']",J Radiat Res,,,True
bf134be7dfc56c7d9a66f0cfe6afc7d3df112b9e,PMC,Epidemiological Determinants of Successful Vaccine Development,http://dx.doi.org/10.7150/ijms.5689,PMC3590596,23471119,CC BY-NC-ND,"Epidemiological determinants of successful vaccine development were explored using measurable biological variables including antigenic stability and requirement of T-cell immunity. Employing a logistic regression model, we demonstrate that a high affinity with blood and immune cells and pathogen interactions (e.g. interference) would be the risk factors of failure for vaccine development.",2013 Feb 21,"['Nishiura, Hiroshi', 'Mizumoto, Kenji']",Int J Med Sci,,,True
9d651ee3cc003d22f9ffff68394494087112ec45,PMC,Complete viral RNA genome sequencing of ultra-low copy samples by sequence-independent amplification,http://dx.doi.org/10.1093/nar/gks794,PMC3592391,22962364,CC BY-NC,"RNA viruses are the causative agents for AIDS, influenza, SARS, and other serious health threats. Development of rapid and broadly applicable methods for complete viral genome sequencing is highly desirable to fully understand all aspects of these infectious agents as well as for surveillance of viral pandemic threats and emerging pathogens. However, traditional viral detection methods rely on prior sequence or antigen knowledge. In this study, we describe sequence-independent amplification for samples containing ultra-low amounts of viral RNA coupled with Illumina sequencing and de novo assembly optimized for viral genomes. With 5 million reads, we capture 96 to 100% of the viral protein coding region of HIV, respiratory syncytial and West Nile viral samples from as little as 100 copies of viral RNA. The methods presented here are scalable to large numbers of samples and capable of generating full or near full length viral genomes from clone and clinical samples with low amounts of viral RNA, without prior sequence information and in the presence of substantial host contamination.",2013 Jan 8,"['Malboeuf, Christine M.', 'Yang, Xiao', 'Charlebois, Patrick', 'Qu, James', 'Berlin, Aaron M.', 'Casali, Monica', 'Pesko, Kendra N.', 'Boutwell, Christian L.', 'DeVincenzo, John P.', 'Ebel, Gregory D.', 'Allen, Todd M.', 'Zody, Michael C.', 'Henn, Matthew R.', 'Levin, Joshua Z.']",Nucleic Acids Res,,,True
6f334216906d370af1b53d8a9cbe88ec25cf0246,PMC,Complete viral RNA genome sequencing of ultra-low copy samples by sequence-independent amplification,http://dx.doi.org/10.1093/nar/gks794,PMC3592391,22962364,CC BY-NC,"RNA viruses are the causative agents for AIDS, influenza, SARS, and other serious health threats. Development of rapid and broadly applicable methods for complete viral genome sequencing is highly desirable to fully understand all aspects of these infectious agents as well as for surveillance of viral pandemic threats and emerging pathogens. However, traditional viral detection methods rely on prior sequence or antigen knowledge. In this study, we describe sequence-independent amplification for samples containing ultra-low amounts of viral RNA coupled with Illumina sequencing and de novo assembly optimized for viral genomes. With 5 million reads, we capture 96 to 100% of the viral protein coding region of HIV, respiratory syncytial and West Nile viral samples from as little as 100 copies of viral RNA. The methods presented here are scalable to large numbers of samples and capable of generating full or near full length viral genomes from clone and clinical samples with low amounts of viral RNA, without prior sequence information and in the presence of substantial host contamination.",2013 Jan 8,"['Malboeuf, Christine M.', 'Yang, Xiao', 'Charlebois, Patrick', 'Qu, James', 'Berlin, Aaron M.', 'Casali, Monica', 'Pesko, Kendra N.', 'Boutwell, Christian L.', 'DeVincenzo, John P.', 'Ebel, Gregory D.', 'Allen, Todd M.', 'Zody, Michael C.', 'Henn, Matthew R.', 'Levin, Joshua Z.']",Nucleic Acids Res,,,False
e008bb9bd16411df2029bfbfd2df3fef72a7e575,PMC,Extreme water-related weather events and waterborne disease,http://dx.doi.org/10.1017/S0950268812001653,PMC3594835,22877498,CC BY-NC-SA,"Global climate change is expected to affect the frequency, intensity and duration of extreme water-related weather events such as excessive precipitation, floods, and drought. We conducted a systematic review to examine waterborne outbreaks following such events and explored their distribution between the different types of extreme water-related weather events. Four medical and meteorological databases (Medline, Embase, GeoRef, PubMed) and a global electronic reporting system (ProMED) were searched, from 1910 to 2010. Eighty-seven waterborne outbreaks involving extreme water-related weather events were identified and included, alongside 235 ProMED reports. Heavy rainfall and flooding were the most common events preceding outbreaks associated with extreme weather and were reported in 55·2% and 52·9% of accounts, respectively. The most common pathogens reported in these outbreaks were Vibrio spp. (21·6%) and Leptospira spp. (12·7%). Outbreaks following extreme water-related weather events were often the result of contamination of the drinking-water supply (53·7%). Differences in reporting of outbreaks were seen between the scientific literature and ProMED. Extreme water-related weather events represent a risk to public health in both developed and developing countries, but impact will be disproportionate and likely to compound existing health disparities.",2013 Apr 9,"['CANN, K. F.', 'THOMAS, D. Rh.', 'SALMON, R. L.', 'WYN-JONES, A. P.', 'KAY, D.']",Epidemiol Infect,,,True
e58abcf656686d9df482b7b9288a61243ba2eb13,PMC,The use of equine influenza pseudotypes for serological screening,,PMC3601075,23515229,CC BY-NC,"Standard assays used for influenza serology present certain practical issues, such as inter-laboratory variability, complex protocols and the necessity for handling certain virus strains in high biological containment facilities. In an attempt to address this, avian and human influenza HA pseudotyped retroviruses have been successfully employed in antibody neutralization assays. In this study we generated an equine influenza pseudotyped lentivirus for serological screening. This was achieved by co-transfection of HEK293T cells with plasmids expressing the haemagglutinin (HA) protein of an H3N8 subtype equine influenza virus strain, HIV gag-pol and firefly luciferase reporter genes and harvesting virus from supernatant. In order to produce infective pseudotype particles it was necessary to additionally co-transfect a plasmid encoding the TMPRSS2 endoprotease to cleave the HA. High titre pseudotype virus (PV) was then used in PV antibody neutralization assays (PVNAs) to successfully distinguish between vaccinated and non-vaccinated equines. The sera were also screened by single radial haemolysis (SRH) assay. There was a 65% correlation between the results of the two assays, with the PVNA assay appearing slightly more sensitive. Future work will extend the testing of the PVNA with a larger number of serum samples to assess sensitivity/specificity, inter/intra-laboratory variability and to define a protective titre.",2012 Dec 31,"['Scott, Simon', 'Molesti, Eleonora', 'Temperton, Nigel', 'Ferrara, Francesca', 'Böttcher-Friebertshäuser, Eva', 'Daly, Janet']",J Mol Genet Med,,,True
6101fcc0282d2e355b5e094de10aafaa05e749c6,PMC,Analysis of the association between necrotizing enterocolitis and transfusion of red blood cell in very low birth weight preterm infants,http://dx.doi.org/10.3345/kjp.2013.56.3.112,PMC3611044,23559972,CC BY-NC,"PURPOSE: To investigate the association between necrotizing enterocolitis (NEC) and red blood cell transfusions in very low birth weight (VLBW) preterm infants. METHODS: We studied were 180 VLBW preterm infants who were admitted to the neonatal intensive care unit of CHA Gangnam Hospital from January of 2006 to December of 2009. The subjects were divided into 2 groups: an NEC group (greater than stage II on the modified Bell's criteria) and a control group (less than stage II on the modified Bell's critieria). We defined red blood cell transfusion before NEC diagnosis as the frequency of transfusion until NEC diagnosis (mean day at NEC diagnosis, day 18) in the NEC group and the frequency of transfusion until 18 days after birth in the control group. RESULTS: Of the 180 subjects, 18 (10%) belonged to the NEC group, and 14 (78%) of these 18 patients had a history of transfusion before NEC diagnosis. The NEC group received 3.1±2.9 transfusions, and the control group received 1.0±1.1 transfusions before the NEC diagnosis (P=0.005). In a multivariate logistic regression corrected for gestational age, Apgar score at 1 minute, the presence of respiratory distress syndrome, patent ductus arteriosus, premature rupture of membrane, disseminated intravascular coagulopathy and death were confounding factors. The risk of NEC increased 1.63 times (95% confidence interval, 1.145 to 2.305; P=0.007) with transfusion before the NEC diagnosis. CONCLUSION: The risk for NEC increased significantly with increased transfusion frequency before the NEC diagnosis.",2013 Mar 18,"['Bak, Seon-Yeong', 'Lee, Sihyoung', 'Park, Jae-Hong', 'Park, Kyu-Hee', 'Jeon, Ji-Hyun']",Korean J Pediatr,,,True
4f8d0dce755f89c22c48c301fe55a457c8ed715b,PMC,Differences between asthmatics and nonasthmatics hospitalised with influenza A infection,http://dx.doi.org/10.1183/09031936.00015512,PMC3612580,22903963,CC BY-NC,"Asthmatics hospitalised because of influenza A infection are less likely to require intensive care or die compared with nonasthmatics. The reasons for this are unknown. We performed a retrospective analysis of data on 1520 patients admitted to 75 UK hospitals with confirmed influenza A/H1N1 2009 infection. A multivariable model was used to investigate reasons for the association between asthma and severe outcomes (intensive care unit support or death). Asthmatics were less likely than nonasthmatics to have severe outcome (11.2% versus 19.8%, unadjusted OR 0.51, 95% CI 0.36–0.72) despite a greater proportion requiring oxygen on admission (36.4% versus 26%, unadjusted OR 1.63) and similar rates of pneumonia (17.1% versus 16.6%, unadjusted OR 1.04). The results of multivariable logistic regression suggest the association of asthma with outcome (adjusted OR 0.62, 95% CI 0.36–1.05; p=0.075) are explained by pre-admission inhaled corticosteroid use (adjusted OR 0.34, 95% CI 0.18–0.66) and earlier admission (≤4 days from symptom onset) (adjusted OR 0.60, 95% CI 0.38–0.94). In asthmatics, systemic corticosteroids were associated with a decreased likelihood of severe outcomes (adjusted OR 0.36, 95% CI 0.18–0.72). Corticosteroid use and earlier hospital admission explained the association of asthma with less severe outcomes in hospitalised patients.",2013 Apr 16,"['Myles, Puja', 'Nguyen-Van-Tam, Jonathan S.', 'Semple, Malcolm G.', 'Brett, Stephen J.', 'Bannister, Barbara', 'Read, Robert C.', 'Taylor, Bruce L.', 'McMenamin, Jim', 'Enstone, Joanne E.', 'Nicholson, Karl G.', 'Openshaw, Peter J.', 'Lim, Wei Shen']",Eur Respir J,,,True
44f01ea111fa2b4bd8ce34739f64b17930bb0ea8,PMC,Pandemic influenza in Papua New Guinea: a modelling study comparison with pandemic spread in a developed country,http://dx.doi.org/10.1136/bmjopen-2012-002518,PMC3612822,23535701,CC BY-NC,"OBJECTIVES: The possible occurrence of a highly pathogenic influenza strain is of concern to health authorities worldwide. It is known that during past influenza pandemics developing countries have experienced considerably higher death rates compared with developed countries. Furthermore, many developing countries lack appropriate pandemic preparedness plans. Mathematical modelling studies to guide the development of such plans are largely focused on predicting pandemic influenza spread in developed nations. However, intervention strategies shown by modelling studies to be highly effective for developed countries give limited guidance as to the impact which an influenza pandemic may have on low-income countries given different demographics and resource constraints. To address this, an individual-based model of a Papua New Guinean (PNG) community was created and used to simulate the spread of a novel influenza strain. The results were compared with those obtained from a comparable Australian model. DESIGN: A modelling study. SETTING: The towns of Madang in PNG (population ∼35 000) and Albany (population ∼30 000) in Australia. OUTCOME MEASURES: Daily and cumulative illness attack rates in both models following introduction of a novel influenza strain into a naive population, for an unmitigated scenario and two social distancing intervention scenarios. RESULTS: The unmitigated scenario indicated an approximately 50% higher attack rate in PNG compared with the Australian model. The two social distancing-based interventions strategies were 60–70% less effective in a PNG setting compared with an Australian setting. CONCLUSIONS: This study provides further evidence that an influenza pandemic occurring in a low-income country such as PNG may have a greater impact than one occurring in a developed country, and that PNG-feasible interventions may be substantially less effective. The larger average household size in PNG, the larger proportion of the population under 18 and greater community-wide contact all contribute to this feature.",2013 Mar 26,"['Milne, George J', 'Baskaran, Pravin', 'Halder, Nilimesh', 'Karl, Stephan', 'Kelso, Joel']",BMJ Open,,,True
013d9fb8719d3d3d47738f9f0604f3b643c4df57,PMC,Pandemic influenza in Papua New Guinea: a modelling study comparison with pandemic spread in a developed country,http://dx.doi.org/10.1136/bmjopen-2012-002518,PMC3612822,23535701,CC BY-NC,"OBJECTIVES: The possible occurrence of a highly pathogenic influenza strain is of concern to health authorities worldwide. It is known that during past influenza pandemics developing countries have experienced considerably higher death rates compared with developed countries. Furthermore, many developing countries lack appropriate pandemic preparedness plans. Mathematical modelling studies to guide the development of such plans are largely focused on predicting pandemic influenza spread in developed nations. However, intervention strategies shown by modelling studies to be highly effective for developed countries give limited guidance as to the impact which an influenza pandemic may have on low-income countries given different demographics and resource constraints. To address this, an individual-based model of a Papua New Guinean (PNG) community was created and used to simulate the spread of a novel influenza strain. The results were compared with those obtained from a comparable Australian model. DESIGN: A modelling study. SETTING: The towns of Madang in PNG (population ∼35 000) and Albany (population ∼30 000) in Australia. OUTCOME MEASURES: Daily and cumulative illness attack rates in both models following introduction of a novel influenza strain into a naive population, for an unmitigated scenario and two social distancing intervention scenarios. RESULTS: The unmitigated scenario indicated an approximately 50% higher attack rate in PNG compared with the Australian model. The two social distancing-based interventions strategies were 60–70% less effective in a PNG setting compared with an Australian setting. CONCLUSIONS: This study provides further evidence that an influenza pandemic occurring in a low-income country such as PNG may have a greater impact than one occurring in a developed country, and that PNG-feasible interventions may be substantially less effective. The larger average household size in PNG, the larger proportion of the population under 18 and greater community-wide contact all contribute to this feature.",2013 Mar 26,"['Milne, George J', 'Baskaran, Pravin', 'Halder, Nilimesh', 'Karl, Stephan', 'Kelso, Joel']",BMJ Open,,,True
1badb9da3cd92175be22f42538742c07f58eb5f8,PMC,Pandemic influenza in Papua New Guinea: a modelling study comparison with pandemic spread in a developed country,http://dx.doi.org/10.1136/bmjopen-2012-002518,PMC3612822,23535701,CC BY-NC,"OBJECTIVES: The possible occurrence of a highly pathogenic influenza strain is of concern to health authorities worldwide. It is known that during past influenza pandemics developing countries have experienced considerably higher death rates compared with developed countries. Furthermore, many developing countries lack appropriate pandemic preparedness plans. Mathematical modelling studies to guide the development of such plans are largely focused on predicting pandemic influenza spread in developed nations. However, intervention strategies shown by modelling studies to be highly effective for developed countries give limited guidance as to the impact which an influenza pandemic may have on low-income countries given different demographics and resource constraints. To address this, an individual-based model of a Papua New Guinean (PNG) community was created and used to simulate the spread of a novel influenza strain. The results were compared with those obtained from a comparable Australian model. DESIGN: A modelling study. SETTING: The towns of Madang in PNG (population ∼35 000) and Albany (population ∼30 000) in Australia. OUTCOME MEASURES: Daily and cumulative illness attack rates in both models following introduction of a novel influenza strain into a naive population, for an unmitigated scenario and two social distancing intervention scenarios. RESULTS: The unmitigated scenario indicated an approximately 50% higher attack rate in PNG compared with the Australian model. The two social distancing-based interventions strategies were 60–70% less effective in a PNG setting compared with an Australian setting. CONCLUSIONS: This study provides further evidence that an influenza pandemic occurring in a low-income country such as PNG may have a greater impact than one occurring in a developed country, and that PNG-feasible interventions may be substantially less effective. The larger average household size in PNG, the larger proportion of the population under 18 and greater community-wide contact all contribute to this feature.",2013 Mar 26,"['Milne, George J', 'Baskaran, Pravin', 'Halder, Nilimesh', 'Karl, Stephan', 'Kelso, Joel']",BMJ Open,,,True
6aaf920479e8c440f99cd8a14a3e9ebd9250d15f,PMC,The human Transmembrane Protease Serine 2 is necessary for the production of Group 2 influenza A virus pseudotypes,,PMC3614188,23577043,CC BY-NC,"The monomer of influenza haemagglutinin is synthesized as a single polypeptide precursor that during maturation is cleaved by proteases into two active subunits. Other studies have demonstrated that the human Transmembrane Protease Serine 2 (TMPRSS2) can cleave the HA of human seasonal influenza viruses. Consequently, we have investigated the use of human Transmembrane Protease Serine 2 to produce high titre influenza haemmagglutinin (HA) lentiviral pseudotypes from Group 2 influenza viruses. Such pseudotypes represent powerful and safe tools to study viral entry and immune responses. Influenza pseudotype particles are obtained by co-transfecting human embryonic kidney HEK293T/17 cells using plasmids coding for the influenza HA, HIV gag-pol and a lentiviral vector incorporating firefly luciferase. However, in order to produce Group 2 pseudotypes, it was necessary to co-transfect a plasmid expressing the TMPRSS2 endoprotease, to achieve the necessary HA cleavage for infective particle generation. These lentiviral pseudotypes were shown to transduce HEK293T/17 cells with high efficiency. This demonstrates that TMPRSS2 is necessary for the functional activation, in vitro, of both the HA of human seasonal influenza and other Group 2 HA influenza strains. Additionally, we show that the Group 2 influenza pseudotype particles can be used as surrogate antigens in neutralization assays and are efficiently neutralized by corresponding influenza virus reference sera. These data demonstrate that the viral pseudotype system is a powerful method for serological surveillance of a wide range of influenza viruses.",2013 Feb 20,"['Ferrara, Francesca', 'Molesti, Eleonora', 'Böttcher-Friebertshäuser, Eva', 'Cattoli, Giovanni', 'Corti, Davide', 'Scott, Simon D', 'Temperton, Nigel J']",J Mol Genet Med,,,True
4bae83e2441c3738d96e49c21c9be0a4c85b4a92,PMC,Protection of chickens against infectious bronchitis virus with a multivalent DNA vaccine and boosting with an inactivated vaccine,http://dx.doi.org/10.4142/jvs.2013.14.1.53,PMC3615232,23388447,CC BY-NC,"The protective efficacy of DNA plasmids encoding avian infectious bronchitis virus (IBV) S1, N, or M protein was investigated in chickens. Chickens were inoculated monovalently (with plasmid pVAX1-16S1, pVAX1-16M, or pVAX1-16N alone) or multivalently (combination of the three different plasmids, pVAX1-16S1/M/N). A prime-boost immunization protocol against IBV was developed. Chickens were immunized with the multivalent DNA vaccine twice and then boosted with an inactivated vaccine once. Antibody titers of the chickens immunized with pVAX1-16S1/M/N were much higher than those of the monovalent groups (p < 0.01). A protective rate up to 90% was observed in the pVAX1-16S1/M/N group. The serum antibody titers in the prime-boost birds were significantly higher than those of the multivalent DNA vaccine group (p < 0.01) but not significantly different compared to the inactivated vaccine group at 49 days of age. Additionally, the prime-boost group also showed the highest level of IBV-specific cellular proliferation compared to the monovalent groups (p < 0.01) but no significant difference was found compared to the multivalent DNA vaccine group, and the prime-boost group completely protected from followed viral challenge.",2013 Mar 24,"['Yan, Fang', 'Zhao, Yujun', 'Hu, Yongting', 'Qiu, Jianyang', 'Lei, Wenxin', 'Ji, Wenhui', 'Li, Xuying', 'Wu, Qian', 'Shi, Xiumin', 'Li, Zhong']",J Vet Sci,,,True
6f5c8e7b610ecc3b139756ce244a25c699d33946,PMC,Fit for the future? The place of global health in the UK's postgraduate medical training: a review,http://dx.doi.org/10.1177/2042533313476421,PMC3616298,23560218,CC BY-NC,"OBJECTIVES: That health is now global is increasingly accepted. However, a ‘mismatch between present professional competencies and the requirements of an increasingly interdependent world’ has been identified. Postgraduate training should take account of the increasingly global nature of health; this paper examines the extent to which they currently do. DESIGN: Trainees across 11 medical specialties reviewed the content of their postgraduate curriculum. SETTING: Not relevant. PARTCIPANTS: None. MAIN OUTCOME MEASURES: Competencies were coded as ‘UK’ (statement only relevant to UK work), ‘global’ (statement with an explicit reference to aspects of health outside the UK) or generic (relevant both to the UK and international settings). RESULTS: Six of the 11 curricula reviewed contained global health competencies. These covered the global burden or determinants of disease and appropriate policy responses. Only one College required trainees to ‘be aware of the World Health Organization’, or ‘know the local, national and international structures for health care’. These cross-cutting competencies have applicability to all specialties. All 11 curricula contained generic competencies where a global health perspective and/or experience could be advantageous, e.g. caring for migrant or culturally different patients. CONCLUSION: Trainees in all specialties should achieve a minimum requirement of global health awareness. This can be achieved through a small number of common competencies that are consistent across core curricula. These should lead on from equivalent undergraduate competencies. Addressing the current gap in the global health content of postgraduate medical curricula will ensure that the UK has health professionals that are trained to meet the health challenges of the future.",2013 Mar 6,"['Hall, JA', 'Brown, CS', 'Pettigrew, L', 'Malik, ANJ', 'Watson, J', 'Topiwala, A', 'McGregor, L', 'Ramsay, R']",JRSM Short Rep,,,True
05cf81cc55f7a6f80902a671cac49d85af9782ed,PMC,The Emergence of Human Coronavirus EMC: How Scared Should We Be?,http://dx.doi.org/10.1128/mBio.00191-13,PMC3622931,23572553,CC BY-NC-SA,"A novel betacoronavirus, human coronavirus (HCoV-EMC), has recently been detected in humans with severe respiratory disease. Further characterization of HCoV-EMC suggests that this virus is different from severe acute respiratory syndrome coronavirus (SARS-CoV) because it is able to replicate in multiple mammalian cell lines and it does not use angiotensin-converting enzyme 2 as a receptor to achieve infection. Additional research is urgently needed to better understand the pathogenicity and tissue tropism of this virus in humans. In their recent study published in mBio, Kindler et al. shed some light on these important topics (E. Kindler, H. R. Jónsdóttir, M. Muth, O. J. Hamming, R. Hartmann, R. Rodriguez, R. Geffers, R. A. Fouchier, C. Drosten, M. A. Müller, R. Dijkman, and V. Thiel, mBio 4[1]:e00611-12, 2013). These authors report the use of differentiated pseudostratified human primary airway epithelial cells, an in vitro model with high physiological relevance to the human airway epithelium, to characterize the cellular tropism of HCoV-EMC. More importantly, the authors demonstrate the potential use of type I and type III interferons (IFNs) to control viral infection.",2013 Apr 9,"['Chan, Renee W. Y.', 'Poon, Leo L. M.']",mBio,,,True
b41638f869301e2af9eef7913301d55516fcf4ce,PMC,A review of vaccine development and research for industry animals in Korea,http://dx.doi.org/10.7774/cevr.2012.1.1.18,PMC3623508,23596575,CC BY-NC,"Vaccination has proven to be the most cost-effective strategy for controlling a wide variety of infectious diseases in humans and animals. For the last decade, veterinary vaccines have been substantially developed and demonstrated their effectiveness against many diseases. Nevertheless, new vaccines are greatly demanded to effectively control newly- and re-emerging pathogens in livestock. However, development of veterinary vaccines is a challenging task, in part, due to a variety of pathogens, hosts, and the uniqueness of host-susceptibility to each pathogen. Therefore, novel concepts of vaccines should be explored to overcome the limitation of conventional vaccines. There have been greatly advanced in the completion of genomic sequencing of pathogens, the application of comparative genomic and transcriptome analysis. This would facilitate to open opportunities up to investigate a new generation of vaccines; recombinant subunit vaccine, virus-like particle, DNA vaccine, and vector-vehicle vaccine. Currently, such types of vaccines are being actively explored against various livestock diseases, affording numerous advantages over conventional vaccines, including ease of production, immunogenicity, safety, and multivalency in a single shot. In this articles, the authors present the current status of the development of veterinary vaccines at large as well as research activities conducted in Korea.",2012 Jul 31,"['Lee, Nak-Hyung', 'Lee, Jung-Ah', 'Park, Seung-Yong', 'Song, Chang-Seon', 'Choi, In-Soo', 'Lee, Joong-Bok']",Clin Exp Vaccine Res,,,True
2dfdbf2d6b77426866feaf93486327d372fd27c7,PMC,The history of vaccination and current vaccination policies in Korea,http://dx.doi.org/10.7774/cevr.2012.1.1.3,PMC3623509,23596573,CC BY-NC,"There may be many reasons for the significant decrease in the incidence of the pediatric infectious diseases in modern Korea; this could be due to the improvement of sanitary facilities, significant growth of Korean economy, improvement of nutrition, development and dissemination of antibiotics and implantation of vaccination, and overall improvement of medical technology. The development of vaccination has been highlighted as a striking achievement of the modern medical sciences with new technologies in many fields of medicine. Since 1876, the method for vaccination has opened its new era by Suk-Young Jee, known as the Jenner in Korea who wrote a book about smallpox vaccination, and it led an opportunity to propagate the needs for the vaccination in Korea. There was a time when pediatric wards were full of patients with parasitic diseases and many vaccine-preventable diseases such as diphtheria, pertussis, Japanese B encephalitis, and poliomyelitis in 1950s-1960s. We do not see those infectious diseases that often any more in recent years. However, we still have patients with water-borne diseases and other communicable diseases related to increasing international travels. We just experienced the first pandemic influenza of the 21st century in 2009 and avian influenza is still a threat to humans in other parts of the world with an unpredictable potential of pandemicity. In addition, we have tough battles with emerging antibiotic resistance in many strains of bacteria and increased opportunistic infections due to improvement of medical technology involving more aggressive treatment modality and use of medical devices. Researches in many areas are under way and we hope that some of them may be preventable and decreased with a development of new vaccines in the future.",2012 Jul 31,"Cha, Sung-Ho",Clin Exp Vaccine Res,,,True
426da8c3fb9c6792b5d26214d55471099877e337,PMC,Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin,http://dx.doi.org/10.1038/srep01686,PMC3629412,23594967,CC BY-NC-SA,"The identification of a novel β coronavirus, nCoV, as the causative agent of severe respiratory illness in humans originating in Saudi Arabia, Qatar and Jordan has raised concerns about the possibility of a coronavirus pandemic similar to that of SARS-CoV. As a definitive treatment regimen has never been thoroughly evaluated for coronavirus infections, there is an urgent need to rapidly identify potential therapeutics to address future cases of nCoV. To determine an intervention strategy, the effect of interferon-α2b and ribavirin on nCoV isolate hCoV-EMC/2012 replication in Vero and LLC-MK2 cells was evaluated. hCoV-EMC/2012 was sensitive to both interferon-α2b and ribavirin alone in Vero and LLC-MK2 cells, but only at relatively high concentrations; however, when combined, lower concentrations of interferon-α2b and ribavirin achieved comparable endpoints. Thus, a combination of interferon-α2b and ribavirin, which are already commonly used in the clinic, may be useful for patient management in the event of future nCoV infections.",2013 Apr 18,"['Falzarano, Darryl', 'de Wit, Emmie', 'Martellaro, Cynthia', 'Callison, Julie', 'Munster, Vincent J.', 'Feldmann, Heinz']",Sci Rep,,,True
4f3e689f3806b2047b5f5a70df6ce9d3581dcc97,PMC,Pathogen–host–environment interplay and disease emergence,http://dx.doi.org/10.1038/emi.2013.5,PMC3630490,26038452,CC BY-NC-ND,"Gaining insight in likely disease emergence scenarios is critical to preventing such events from happening. Recent focus has been on emerging zoonoses and on identifying common patterns and drivers of emerging diseases. However, no overarching framework exists to integrate knowledge on all emerging infectious disease events. Here, we propose such a conceptual framework based on changes in the interplay of pathogens, hosts and environment that lead to the formation of novel disease patterns and pathogen genetic adjustment. We categorize infectious disease emergence events into three groups: (i) pathogens showing up in a novel host, ranging from spill-over, including zoonoses, to complete species jumps; (ii) mutant pathogens displaying novel traits in the same host, including an increase in virulence, antimicrobial resistance and host immune escape; and (iii) disease complexes emerging in a new geographic area, either through range expansion or through long distance jumps. Each of these categories is characterized by a typical set of drivers of emergence, matching pathogen trait profiles, disease ecology and transmission dynamics. Our framework may assist in disentangling and structuring the rapidly growing amount of available information on infectious diseases. Moreover, it may contribute to a better understanding of how human action changes disease landscapes globally.",2013 Feb 6,"['Engering, Anneke', 'Hogerwerf, Lenny', 'Slingenbergh, Jan']",Emerg Microbes Infect,,,True
3b69d402abfb10509e1518f2f2b38e8d8840f34e,PMC,Emerging virus diseases: can we ever expect the unexpected?,http://dx.doi.org/10.1038/emi.2012.47,PMC3630908,26038413,CC BY-NC-ND,"Emerging virus diseases are a major threat to human and veterinary public health. With new examples occurring approximately one each year, the majority are viruses originating from an animal host. Of the many factors responsible, changes to local ecosystems that perturb the balance between pathogen and principal host species is one of the major drivers, together with increasing urbanization of mankind and changes in human behavior. Many emerging viruses have RNA genomes and as such are capable of rapid mutation and selection of new variants in the face of environmental changes in host numbers and available target species. This review summarizes recent work on aspects of virus emergence and the current understanding of the molecular and immunological basis whereby viruses may cross between species and become established in new ecological niches. Emergence is hard to predict, although mathematical modeling and spatial epidemiology have done much to improve the prediction of where emergence may occur. However, much needs to be done to ensure adequate surveillance is maintained of animal species known to present the greatest risk thus increasing general alertness among physicians, veterinarians and those responsible for formulating public health policy.",2012 Dec 26,"['Howard, Colin R', 'Fletcher, Nicola F']",Emerg Microbes Infect,,,True
95d1e1fce153b741c5b0f3bd1412e6ba3412ecf7,PMC,Welcome from the Editors-in-Chief,http://dx.doi.org/10.1038/emi.2012.13,PMC3630911,26038415,CC BY-NC-ND,,2012 Jul 11,"['Wen, Yu-Mei', 'Klenk, Hans-Dieter']",Emerg Microbes Infect,,,False
7e92581ed1b5f05b3002790d3cd71974982f7a3f,PMC,Receptor-binding domains of spike proteins of emerging or re-emerging viruses as targets for development of antiviral vaccines,http://dx.doi.org/10.1038/emi.2012.1,PMC3630917,26038424,CC BY-NC-ND,"A number of emerging and re-emerging viruses have caused epidemics or pandemics of infectious diseases leading to major devastations throughout human history. Therefore, developing effective and safe vaccines against these viruses is clearly important for the protection of at-risk populations. Our previous studies have shown that the receptor-binding domain (RBD) in the spike protein of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) is a key target for the development of SARS vaccines. In this review, we highlight some key advances in the development of antiviral vaccines targeting the RBDs of spike proteins of emerging and re-emerging viruses, using SARS-CoV, influenza virus, Hendra virus (HeV) and Nipah virus (NiV) as examples.",2012 Aug 8,"['Jiang, Shibo', 'Lu, Lu', 'Liu, Qi', 'Xu, Wei', 'Du, Lanying']",Emerg Microbes Infect,,,True
35ec885b13ad96752433a085e543db81dd1d80df,PMC,Genetic relatedness of the novel human group C betacoronavirus to Tylonycteris bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5,http://dx.doi.org/10.1038/emi.2012.45,PMC3630921,26038405,CC BY-NC-ND,"The recent outbreak of severe respiratory infections associated with a novel group C betacoronavirus (HCoV-EMC) from Saudi Arabia has drawn global attention to another highly probable “SARS-like” animal-to-human interspecies jumping event in coronavirus (CoV). The genome of HCoV-EMC is most closely related to Tylonycteris bat coronavirus HKU4 (Ty-BatCoV HKU4) and Pipistrellus bat coronavirus HKU5 (Pi-BatCoV HKU5) we discovered in 2006. Phylogenetically, HCoV-EMC is clustered with Ty-BatCoV HKU4/Pi-BatCoV HKU5 with high bootstrap supports, indicating that HCoV-EMC is a group C betaCoV. The major difference between HCoV-EMC and Ty-BatCoV HKU4/Pi-BatCoV HKU5 is in the region between S and E, where HCoV-EMC possesses five ORFs (NS3a-NS3e) instead of four, with low (31%–62%) amino acid identities to Ty-BatCoV HKU4/Pi-BatCoV HKU5. Comparison of the seven conserved replicase domains for species demarcation shows that HCoV-EMC is a novel CoV species. More intensive surveillance studies in bats and other animals may reveal the natural host of HCoV-EMC.",2012 Nov 7,"['Woo, Patrick CY', 'Lau, Susanna KP', 'Li, Kenneth SM', 'Tsang, Alan KL', 'Yuen, Kwok-Yung']",Emerg Microbes Infect,,,True
9209041d93cd781cde415406283ebad549610042,PMC,Biosecurity and biosafety in research on emerging pathogens,http://dx.doi.org/10.1038/emi.2012.39,PMC3630924,26038411,CC BY-NC-ND,,2012 Nov 21,"['Lu, Lu', 'Liu, Qi', 'Jiang, Shibo']",Emerg Microbes Infect,,,True
7f37181b66f15b8ca2d62b6943d9a6f92e843a66,PMC,"In memory of Patrick Manson, founding father of tropical medicine and the discovery of vector-borne infections",http://dx.doi.org/10.1038/emi.2012.32,PMC3630944,26038403,CC BY-NC-ND,"Patrick Manson, a clinician-scientist serving in China (1866–1889), discovered that many tropical infectious diseases require a vector peculiar to warm climate for person to person transmission. He demonstrated the nocturnal periodicity of microfilariae in the blood of patients with elephantiasis. These microfilariae undergo metamorphosis when ingested by the mosquito acting as the vector for the completion of their life cycle. Furthermore, he demonstrated the linkage between the lung fluke and endemic haemoptysis by finding operculated eggs in patients' sputa. He predicted that the miracidium from hatched eggs uses crustaceans, such as fresh-water snails found at tropical conditions, as the intermediate hosts in the life cycle of many trematodes. His vector hypothesis leads to vector control which is now the cornerstone for the World Health Organization's programme for the elimination/control of lymphatic filariasis, dracunculiasis and malaria. Before leaving China, he established the Alice Memorial Hospital, the Hong Kong College of Medicine for Chinese (the forerunner of the University of Hong Kong), and the Hong Kong Medical Society for medical service and education. He also incepted the Hong Kong Dairy Farm for supplying hygienic milk affordable by pregnant women, children and patients.",2012 Oct 24,"['To, Kelvin KW', 'Yuen, Kwok-Yung']",Emerg Microbes Infect,,,True
6ae4586f198b9710e0285939e265149fbdb3bdab,PMC,Immunity toward H1N1 influenza hemagglutinin of historical and contemporary strains suggests protection and vaccine failure,http://dx.doi.org/10.1038/srep01698,PMC3633051,23608887,CC BY-NC-ND,"Evolution of H1N1 influenza A outbreaks of the past 100 years is interesting and significantly complex and details of H1N1 genetic drift remains unknown. Here we investigated the clinical characteristics and immune cross-reactivity of significant historical H1N1 strains. We infected ferrets with H1N1 strains from 1943, 1947, 1977, 1986, 1999, and 2009 and showed each produced a unique clinical signature. We found significant cross-reactivity between viruses with similar HA sequences. Interestingly, A/FortMonmouth/1/1947 antisera cross-reacted with A/USSR/90/1977 virus, thought to be a 1947 resurfaced virus. Importantly, our immunological data that didn't show cross-reactivity can be extrapolated to failure of past H1N1 influenza vaccines, ie. 1947, 1986 and 2009. Together, our results help to elucidate H1N1 immuno-genetic alterations that occurred in the past 100 years and immune responses caused by H1N1 evolution. This work will facilitate development of future influenza therapeutics and prophylactics such as influenza vaccines.",2013 Apr 23,"['Huang, Stephen S. H.', 'Lin, Zhen', 'Banner, David', 'León, Alberto J.', 'Paquette, Stéphane G.', 'Rubin, Barry', 'Rubino, Salvatore', 'Guan, Yi', 'Kelvin, David J.', 'Kelvin, Alyson A.']",Sci Rep,,,True
cb71c5b05e1ef68cec084a8206fd7206f16d214d,PMC,Immunity toward H1N1 influenza hemagglutinin of historical and contemporary strains suggests protection and vaccine failure,http://dx.doi.org/10.1038/srep01698,PMC3633051,23608887,CC BY-NC-ND,"Evolution of H1N1 influenza A outbreaks of the past 100 years is interesting and significantly complex and details of H1N1 genetic drift remains unknown. Here we investigated the clinical characteristics and immune cross-reactivity of significant historical H1N1 strains. We infected ferrets with H1N1 strains from 1943, 1947, 1977, 1986, 1999, and 2009 and showed each produced a unique clinical signature. We found significant cross-reactivity between viruses with similar HA sequences. Interestingly, A/FortMonmouth/1/1947 antisera cross-reacted with A/USSR/90/1977 virus, thought to be a 1947 resurfaced virus. Importantly, our immunological data that didn't show cross-reactivity can be extrapolated to failure of past H1N1 influenza vaccines, ie. 1947, 1986 and 2009. Together, our results help to elucidate H1N1 immuno-genetic alterations that occurred in the past 100 years and immune responses caused by H1N1 evolution. This work will facilitate development of future influenza therapeutics and prophylactics such as influenza vaccines.",2013 Apr 23,"['Huang, Stephen S. H.', 'Lin, Zhen', 'Banner, David', 'León, Alberto J.', 'Paquette, Stéphane G.', 'Rubin, Barry', 'Rubino, Salvatore', 'Guan, Yi', 'Kelvin, David J.', 'Kelvin, Alyson A.']",Sci Rep,,,False
8f73d388e9ac6eedc6e60400d1fc7e3809814042,PMC,Future vaccines for a globalized world,http://dx.doi.org/10.1038/emi.2012.17,PMC3634133,26038417,CC BY-NC-ND,,2012 Jul 11,"['Babiuk, Lorne A', 'Gerdts, Volker']",Emerg Microbes Infect,,,True
f7bbdd316b8d64ca1001b67b96c06efd531893b6,PMC,Tools to Detect Influenza Virus,http://dx.doi.org/10.3349/ymj.2013.54.3.560,PMC3635619,23549796,CC BY-NC,"In 2009, pandemic influenza A (H1N1) virus (H1N1 09) started to spread quickly in many countries. It causes respiratory infection with signs and symptoms of common infectious agents. Thus, clinicians sometimes may miss the H1N1 patient. Clinical laboratory tests are important for the diagnosis of the H1N1 infection. There are several tests available, however, the rapid test and direct fluorescence antigen test are unable to rule out the influenza virus infection and viral culture test is time consuming. Therefore, nucleic acid amplification techniques based on reverse transcription polymerase chain reaction assays are regarded as a specific diagnosis to confirm the influenza virus infection. Although the nucleic acid-based techniques are highly sensitive and specific, the high mutation rate of the influenza RNA-dependent RNA polymerase could limit the utility of the techniques. In addition, their use depends on the availability, cost and throughput of the diagnostic techniques. To overcome these drawbacks, evaluation and development of the techniques should be continued. This review provides an overview of various techniques for specific diagnosis of influenza infection.",2013 May 1,"['Kim, Dae-Ki', 'Poudel, Barun']",Yonsei Med J,,,True
3fa8abac6ce337d7597f4c0d4adac979c4e0b9b7,PMC,Understanding the T cell immune response in SARS coronavirus infection,http://dx.doi.org/10.1038/emi.2012.26,PMC3636424,26038429,CC BY-NC-ND,"The severe acute respiratory syndrome (SARS) epidemic started in late 2002 and swiftly spread across 5 continents with a mortality rate of around 10%. Although the epidemic was eventually controlled through the implementation of strict quarantine measures, there continues a need to investigate the SARS coronavirus (SARS-CoV) and develop interventions should it re-emerge. Numerous studies have shown that neutralizing antibodies against the virus can be found in patients infected with SARS-CoV within days upon the onset of illness and lasting up to several months. In contrast, there is little data on the kinetics of T cell responses during SARS-CoV infection and little is known about their role in the recovery process. However, recent studies in mice suggest the importance of T cells in viral clearance during SARS-CoV infection. Moreover, a growing number of studies have investigated the memory T cell responses in recovered SARS patients. This review covers the available literature on the emerging importance of T cell responses in SARS-CoV infection, particularly on the mapping of cytotoxic T lymphocyte (CTL) epitopes, longevity, polyfunctionality and human leukocyte antigen (HLA) association as well as their potential implications on treatment and vaccine development.",2012 Sep 5,"['Janice Oh, Hsueh-Ling', 'Ken-En Gan, Samuel', 'Bertoletti, Antonio', 'Tan, Yee-Joo']",Emerg Microbes Infect,,,True
bf573e1259148bb11f71b1dce3ad11c0a091ce36,PMC,H7N9 avian influenza virus - search and re-search,http://dx.doi.org/10.1038/emi.2013.18,PMC3636592,26038459,CC BY-NC-ND,,2013 Apr 10,"['Wen, Yu-Mei', 'Klenk, Hans-Dieter']",Emerg Microbes Infect,,,True
0f9341750af1f556fdfee5d61d707278005663ca,PMC,A fatal case caused by novel H7N9 avian influenza A virus in China,http://dx.doi.org/10.1038/emi.2013.22,PMC3636593,26038460,CC BY-NC-ND,,2013 Apr 10,"['Yang, Feifei', 'Wang, Jiali', 'Jiang, Lin', 'Jin, Jialin', 'Shao, Lingyun', 'Zhang, Ying', 'Zhang, Jiming', 'Weng, Xinhua', 'Chen, Shu', 'Zhang, Wenhong']",Emerg Microbes Infect,,,True
7089e8b9423d428a8e1539366978157492f89f19,PMC,Structural complexity of Dengue virus untranslated regions: cis-acting RNA motifs and pseudoknot interactions modulating functionality of the viral genome,http://dx.doi.org/10.1093/nar/gkt203,PMC3643606,23531545,CC BY-NC,"The Dengue virus (DENV) genome contains multiple cis-acting elements required for translation and replication. Previous studies indicated that a 719-nt subgenomic minigenome (DENV-MINI) is an efficient template for translation and (−) strand RNA synthesis in vitro. We performed a detailed structural analysis of DENV-MINI RNA, combining chemical acylation techniques, Pb(2+) ion-induced hydrolysis and site-directed mutagenesis. Our results highlight protein-independent 5′–3′ terminal interactions involving hybridization between recognized cis-acting motifs. Probing analyses identified tandem dumbbell structures (DBs) within the 3′ terminus spaced by single-stranded regions, internal loops and hairpins with embedded GNRA-like motifs. Analysis of conserved motifs and top loops (TLs) of these dumbbells, and their proposed interactions with downstream pseudoknot (PK) regions, predicted an H-type pseudoknot involving TL1 of the 5′ DB and the complementary region, PK2. As disrupting the TL1/PK2 interaction, via ‘flipping’ mutations of PK2, previously attenuated DENV replication, this pseudoknot may participate in regulation of RNA synthesis. Computer modeling implied that this motif might function as autonomous structural/regulatory element. In addition, our studies targeting elements of the 3′ DB and its complementary region PK1 indicated that communication between 5′–3′ terminal regions strongly depends on structure and sequence composition of the 5′ cyclization region.",2013 May 26,"['Sztuba-Solinska, Joanna', 'Teramoto, Tadahisa', 'Rausch, Jason W.', 'Shapiro, Bruce A.', 'Padmanabhan, Radhakrishnan', 'Le Grice, Stuart F. J.']",Nucleic Acids Res,,,True
fdbf1277399517ccdcd4dd23283e190c90adaafd,PMC,Structural complexity of Dengue virus untranslated regions: cis-acting RNA motifs and pseudoknot interactions modulating functionality of the viral genome,http://dx.doi.org/10.1093/nar/gkt203,PMC3643606,23531545,CC BY-NC,"The Dengue virus (DENV) genome contains multiple cis-acting elements required for translation and replication. Previous studies indicated that a 719-nt subgenomic minigenome (DENV-MINI) is an efficient template for translation and (−) strand RNA synthesis in vitro. We performed a detailed structural analysis of DENV-MINI RNA, combining chemical acylation techniques, Pb(2+) ion-induced hydrolysis and site-directed mutagenesis. Our results highlight protein-independent 5′–3′ terminal interactions involving hybridization between recognized cis-acting motifs. Probing analyses identified tandem dumbbell structures (DBs) within the 3′ terminus spaced by single-stranded regions, internal loops and hairpins with embedded GNRA-like motifs. Analysis of conserved motifs and top loops (TLs) of these dumbbells, and their proposed interactions with downstream pseudoknot (PK) regions, predicted an H-type pseudoknot involving TL1 of the 5′ DB and the complementary region, PK2. As disrupting the TL1/PK2 interaction, via ‘flipping’ mutations of PK2, previously attenuated DENV replication, this pseudoknot may participate in regulation of RNA synthesis. Computer modeling implied that this motif might function as autonomous structural/regulatory element. In addition, our studies targeting elements of the 3′ DB and its complementary region PK1 indicated that communication between 5′–3′ terminal regions strongly depends on structure and sequence composition of the 5′ cyclization region.",2013 May 26,"['Sztuba-Solinska, Joanna', 'Teramoto, Tadahisa', 'Rausch, Jason W.', 'Shapiro, Bruce A.', 'Padmanabhan, Radhakrishnan', 'Le Grice, Stuart F. J.']",Nucleic Acids Res,,,False
3d6462be232a3f4b4aab41386a74bb8e6a118b44,PMC,"Incidence and Mortality Rates of Disasters and Mass Casualty Incidents in Korea: A Population-Based Cross-Sectional Study, 2000-2009",http://dx.doi.org/10.3346/jkms.2013.28.5.658,PMC3653076,23678255,CC BY-NC,"The objective of study was to evaluate the incidence and mortality rates of disasters and mass casualty incidents (MCIs) over the past 10 yr in the administrative system of Korea administrative system and to examine their relationship with population characteristics. This was a population-based cross-sectional study. We calculated the nationwide incidence, as well as the crude mortality and injury incidence rates, of disasters and MCIs. The data were collected from the administrative database of the National Emergency Management Agency (NEMA) and from provincial fire departments from January 2000 to December 2009. A total of 47,169 events were collected from the NEMA administrative database. Of these events, 115 and 3,079 cases were defined as disasters and MCIs that occurred in Korea, respectively. The incidence of technical disasters/MCIs was approximately 12.7 times greater than that of natural disasters/MCIs. Over the past 10 yr, the crude mortality rates for disasters and MCIs were 2.36 deaths per 100,000 persons and 6.78 deaths per 100,000 persons, respectively. The crude injury incidence rates for disasters and MCIs were 25.47 injuries per 100,000 persons and 152 injuries per 100,000 persons, respectively. The incidence and mortality of disasters/MCIs in Korea seem to be low compared to that of trend around the world.",2013 May 2,"['Kim, Soo Jin', 'Kim, Chu Hyun', 'Shin, Sang Do', 'Lee, Seung Chul', 'Park, Ju Ok', 'Sung, Joohon']",J Korean Med Sci,,,True
2ff89400f9bff213ae066c12daa59d5a40fa6257,PMC,Chloroquine diphosphate: a risk factor for herpes zoster in patients with dermatomyositis/polymyositis,http://dx.doi.org/10.6061/clinics/2013(05)07,PMC3654292,23778404,CC BY-NC,"OBJECTIVES: Herpes zoster has been widely described in the context of different systemic autoimmune diseases but not dermatomyositis/polymyositis. Therefore, we analyzed the prevalence, risk factors and herpes zoster outcomes in this population. METHOD: A retrospective cohort study of herpes zoster infections in dermatomyositis/polymyositis patients was performed. The patients were followed at a tertiary center from 1991 to 2012. For the control group, each patient with herpes zoster was paired with two patients without herpes zoster. Patients were matched by gender and the type of myositis, age at myositis onset and disease duration. RESULTS: Of 230 patients, 24 (10.4%) had a histories of herpes zoster (19 with dermatomyositis and five with polymyositis, two-thirds female). The mean age of the patients with herpes zoster was 44.6±16.8 years. No difference between the groups was found regarding cumulative clinical manifestations. Disease activity, autoantibody, muscle and leukogram parameters were also comparable between the groups. No differences in immunosuppressive (alone or in association with other immunosuppressive therapies) or glucocorticoid (current use, medium dose and cumulative dose in the last two months) therapies were found between patients with and without herpes zoster. However, a higher proportion of patients in the herpes zoster group received chloroquine diphosphate compared to the control group. All of the patients received acyclovir; 58.3% of patients had postherpetic neuralgia and no cases of recurrence were reported. Furthermore, individuals who were taking high prednisone doses at the time of the herpes zoster diagnosis had reduced levels of postherpetic neuralgia. CONCLUSIONS: These data suggest that chloroquine diphosphate could predispose patients with dermatomyositis/polymyositis to developing herpes zoster, particularly women and dermatomyositis patients.",2013 May,"['da Cunha, Gilmara Franco', 'de Souza, Fernando Henrique Carlos', 'Levy-Neto, Maurício', 'Shinjo, Samuel Katsuyuki']",Clinics (Sao Paulo),,,True
c445a1425736c454dd61d836d8f657dda8b1b104,PMC,Is patient isolation the single most important measure to prevent the spread of multidrug-resistant pathogens?,http://dx.doi.org/10.4161/viru.22641,PMC3654617,23302791,CC BY-NC,"Isolation or cohorting of infected patients is an old concept. Its purpose is to prevent the transmission of microorganisms from infected or colonized patients to other patients, hospital visitors, and health care workers, who may subsequently transmit them to other patients or become infected or colonized themselves. Because the process of isolating patients is expensive, time-consuming, often uncomfortable for patients and may impede care, it should be implemented only when necessary. Conversely, failure to isolate a patient with multidrug-resistant microorganisms may lead to adverse outcomes, and may ultimately be expensive when one considers the direct costs of an outbreak investigation and the indirect costs of lost productivity. In this review, we argue that contact precautions are essential to control the spread of epidemic and endemic multidrug-resistant microorganisms, and discuss limitations of some available data.",2013 Feb 15,"['Landelle, Caroline', 'Pagani, Leonardo', 'Harbarth, Stephan']",Virulence,,,True
98788dfeef7084c7c15a66c0f83b521f586bdde0,PMC,Reovirus Activates a Caspase-Independent Cell Death Pathway,http://dx.doi.org/10.1128/mBio.00178-13,PMC3656442,23674612,CC BY-NC-SA,"Virus-induced apoptosis is thought to be the primary mechanism of cell death following reovirus infection. Induction of cell death following reovirus infection is initiated by the incoming viral capsid proteins during cell entry and occurs via NF-κB-dependent activation of classical apoptotic pathways. Prototype reovirus strain T3D displays a higher cell-killing potential than strain T1L. To investigate how signaling pathways initiated by T3D and T1L differ, we methodically analyzed cell death pathways activated by these two viruses in L929 cells. We found that T3D activates NF-κB, initiator caspases, and effector caspases to a significantly greater extent than T1L. Surprisingly, blockade of NF-κB or caspases did not affect T3D-induced cell death. Cell death following T3D infection resulted in a reduction in cellular ATP levels and was sensitive to inhibition of the kinase activity of receptor interacting protein 1 (RIP1). Furthermore, membranes of T3D-infected cells were compromised. Based on the dispensability of caspases, a requirement for RIP1 kinase function, and the physiological status of infected cells, we conclude that reovirus can also induce an alternate, necrotic form of cell death described as necroptosis. We also found that induction of necroptosis requires synthesis of viral RNA or proteins, a step distinct from that necessary for the induction of apoptosis. Thus, our studies reveal that two different events in the reovirus replication cycle can injure host cells by distinct mechanisms.",2013 May 14,"['Berger, Angela K.', 'Danthi, Pranav']",mBio,,,True
4edda548e89522b4df20e723e29c63f309857b10,PMC,Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus,http://dx.doi.org/10.1128/mBio.00165-13,PMC3663187,23631916,CC BY-NC-SA,"A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus.",2013 Apr 30,"['Josset, Laurence', 'Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Agnihothram, Sudhakar', 'Sova, Pavel', 'Carter, Victoria S.', 'Yount, Boyd L.', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Katze, Michael G.']",mBio,,,True
17114faf3bbc2a82ef49762ce4f3f922cb213f4e,PMC,Laser microporation of the skin: prospects for painless application of protective and therapeutic vaccines,http://dx.doi.org/10.1517/17425247.2013.773970,PMC3667678,23425032,CC BY-NC,"INTRODUCTION: In contrast to muscle and subcutaneous tissue, the skin is easily accessible and provides unique immunological properties. Increasing knowledge about the complex interplay of skin-associated cell types in the development of cutaneous immune responses has fueled efforts to target the skin for vaccination as well as for immunotherapy. AREAS COVERED: This review provides an overview on skin layers and their resident immunocompetent cell types. Advantages and shortcomings of standard methods and innovative technologies to circumvent the outermost skin barrier are addressed. Studies employing fractional skin ablation by infrared lasers for cutaneous delivery of drugs, as well as high molecular weight molecules such as protein antigens or antibodies, are reviewed, and laserporation is introduced as a versatile transcutaneous vaccination platform. Specific targeting of the epidermis or the dermis by different laser settings, the resulting kinetics of uptake and transport and the immune response types elicited are discussed, and the potential of this transcutaneous delivery platform for allergen-specific immunotherapy is demonstrated. EXPERT OPINION: Needle-free and painless vaccination approaches have the potential to replace standard methods due to their improved safety and optimal patient compliance. The use of fractional laser devices for stepwise ablation of skin layers might be advantageous for both vaccination against microbial pathogens, as well as immunotherapeutic approaches, such as allergen-specific immunotherapy. Thorough investigation of the underlying immunological mechanisms will help to provide the knowledge for a rational design of transcutaneous protective/therapeutic vaccines.",2013 Jun 21,"['Scheiblhofer, Sandra', 'Thalhamer, Josef', 'Weiss, Richard']",Expert Opin Drug Deliv,,,True
a26ffcce0878ea2ebab2a7ed46a9761244fda936,PMC,Effectiveness of adjuvanted seasonal influenza vaccines (Inflexal V(®) and Fluad(®)) in preventing hospitalization for influenza and pneumonia in the elderly: A matched case-control study,http://dx.doi.org/10.4161/hv.22231,PMC3667930,23143775,CC BY-NC,"Annual vaccination is the main mean of preventing influenza in the elderly. In order to evaluate the effectiveness of the adjuvanted seasonal influenza vaccines available in Italy in preventing hospitalization for influenza and pneumonia, a matched case-control study was performed in elderly subjects during the 2010–2011 season in Genoa (Italy). Cases and controls were matched in a 1:1 ratio according to gender, age, socio-economic status and type of influenza vaccine. Vaccine effectiveness was calculated as IVE = [(1-OR)x100] and crude odds ratios were estimated through conditional logistic regression models. Adjusted odds ratios were estimated through multivariable logistic models. In the study area, influenza activity was moderate in the 2010–2011 season, with optimal matching between circulating viruses and vaccine strains. We recruited 187 case-control pairs; 46.5% of cases and 79.1% of controls had been vaccinated. The adjuvanted influenza vaccines (Fluad(®) considered together with Inflexal V(®)) were associated with a significant reduction in the risk of hospitalization, their effectiveness being 94.8% (CI 77.1–98.8). Adjusted vaccine effectiveness was 95.2% (CI 62.8–99.4) and 87.8 (CI 0.0–98.9) for Inflexal V(®) and Fluad(®), respectively. Both adjuvanted vaccines proved effective, although the results displayed statistical significance only for Inflexal V(®) (p = 0.004), while for Fluad(®) statistical significance was not reached (p = 0.09). Our study is the first to provide information on the effectiveness of Inflexal V(®) in terms of reducing hospitalizations for influenza or pneumonia in the elderly, and demonstrates that this vaccine yields a high degree of protection and that its use would generate considerable saving for the National Health Service.",2013 Jan 1,"['Gasparini, Roberto', 'Amicizia, Daniela', 'Lai, Piero Luigi', 'Rossi, Stefania', 'Panatto, Donatella']",Hum Vaccin Immunother,,,True
e0187a691be1237e922515d56bcfbc7ec988fa3e,PMC,Glucose 6-phosphate dehydrogenase deficiency enhances germ cell apoptosis and causes defective embryogenesis in Caenorhabditis elegans,http://dx.doi.org/10.1038/cddis.2013.132,PMC3674345,23640458,CC BY-NC-ND,"Glucose 6-phosphate dehydrogenase (G6PD) deficiency, known as favism, is classically manifested by hemolytic anemia in human. More recently, it has been shown that mild G6PD deficiency moderately affects cardiac function, whereas severe G6PD deficiency leads to embryonic lethality in mice. How G6PD deficiency affects organisms has not been fully elucidated due to the lack of a suitable animal model. In this study, G6PD-deficient Caenorhabditis elegans was established by RNA interference (RNAi) knockdown to delineate the role of G6PD in animal physiology. Upon G6PD RNAi knockdown, G6PD activity was significantly hampered in C. elegans in parallel with increased oxidative stress and DNA oxidative damage. Phenotypically, G6PD-knockdown enhanced germ cell apoptosis (2-fold increase), reduced egg production (65% of mock), and hatching (10% of mock). To determine whether oxidative stress is associated with G6PD knockdown-induced reproduction defects, C. elegans was challenged with a short-term hydrogen peroxide (H(2)O(2)). The early phase egg production of both mock and G6PD-knockdown C. elegans were significantly affected by H(2)O(2). However, H(2)O(2)-induced germ cell apoptosis was more dramatic in mock than that in G6PD-deficient C. elegans. To investigate the signaling pathways involved in defective oogenesis and embryogenesis caused by G6PD knockdown, mutants of p53 and mitogen-activated protein kinase (MAPK) pathways were examined. Despite the upregulation of CEP-1 (p53), cep-1 mutation did not affect egg production and hatching in G6PD-deficient C. elegans. Neither pmk-1 nor mek-1 mutation significantly affected egg production, whereas sek-1 mutation further decreased egg production in G6PD-deficient C. elegans. Intriguingly, loss of function of sek-1 or mek-1 dramatically rescued defective hatching (8.3- and 9.6-fold increase, respectively) induced by G6PD knockdown. Taken together, these findings show that G6PD knockdown reduces egg production and hatching in C. elegans, which are possibly associated with enhanced oxidative stress and altered MAPK pathways, respectively.",2013 May 2,"['Yang, H-C', 'Chen, T-L', 'Wu, Y-H', 'Cheng, K-P', 'Lin, Y-H', 'Cheng, M-L', 'Ho, H-Y', 'Lo, S J', 'Chiu, D T-Y']",Cell Death Dis,,,True
be0d6fb3b99b467756a0f5a26e3976a91d49ec2e,PMC,Virus ecology: a gap between detection and prediction,http://dx.doi.org/10.1038/emi.2013.25,PMC3675401,26038466,CC BY-NC-ND,,2013 May 22,"Drosten, Christian",Emerg Microbes Infect,,,True
d08bd8440ea92be5251562480f44eb57ae84f498,PMC,Severe Fever with Thrombocytopenia Syndrome: Tick-Mediated Viral Disease,http://dx.doi.org/10.3346/jkms.2013.28.6.795,PMC3677989,23772137,CC BY-NC,,2013 Jun 3,"['Chang, Mee Soo', 'Woo, Jun Hee']",J Korean Med Sci,,,True
310e6155d1d7856c824b0304dea2ca5ec637c2bf,PMC,Helicobacter pylori VacA Suppresses Lactobacillus acidophilus-Induced Interferon Beta Signaling in Macrophages via Alterations in the Endocytic Pathway,http://dx.doi.org/10.1128/mBio.00609-12,PMC3685213,23760466,CC BY-NC-SA,"Helicobacter pylori causes chronic gastritis and avoids elimination by the immune system of the infected host. The commensal bacterium Lactobacillus acidophilus has been suggested to exert beneficial effects as a supplement during H. pylori eradication therapy. In the present study, we applied whole-genome microarray analysis to compare the immune responses induced in murine bone marrow-derived macrophages (BMDMs) stimulated with L. acidophilus, H. pylori, or both bacteria in combination. While L. acidophilus induced a Th1-polarizing response characterized by high expression of interferon beta (IFN-β) and interleukin 12 (IL-12), H. pylori strongly induced the innate cytokines IL-1β and IL-1α. In BMDMs prestimulated with L. acidophilus, H. pylori blocked the expression of L. acidophilus-induced IFN-β and IL-12 and suppressed the expression of key regulators of the Rho, Rac, and Cdc42 GTPases. The inhibition of L. acidophilus-induced IFN-β was independent of H. pylori viability and the virulence factor CagPAI; however, a vacuolating cytotoxin (vacA) mutant was unable to block IFN-β. Confocal microscopy demonstrated that the addition of H. pylori to L. acidophilus-stimulated BMDMs redirects intracellular processing, leading to an accumulation of L. acidophilus in the endosomal and lysosomal compartments. Thus, our findings indicate that H. pylori inhibits the development of a strong Th1-polarizing response in BMDMs stimulated with L. acidophilus by blocking the production of IFN-β in a VacA-dependent manner. We suggest that this abrogation is caused by a redirection of the endocytotic pathway in the processing of L. acidophilus.",2013 Jun 11,"['Weiss, Gudrun', 'Forster, Sam', 'Irving, Aaron', 'Tate, Michelle', 'Ferrero, Richard L.', 'Hertzog, Paul', 'Frøkiær, Hanne', 'Kaparakis-Liaskos, Maria']",mBio,,,True
61316d789f66022b466f2924837aaff7f0bf65f5,PMC,Helicobacter pylori VacA Suppresses Lactobacillus acidophilus-Induced Interferon Beta Signaling in Macrophages via Alterations in the Endocytic Pathway,http://dx.doi.org/10.1128/mBio.00609-12,PMC3685213,23760466,CC BY-NC-SA,"Helicobacter pylori causes chronic gastritis and avoids elimination by the immune system of the infected host. The commensal bacterium Lactobacillus acidophilus has been suggested to exert beneficial effects as a supplement during H. pylori eradication therapy. In the present study, we applied whole-genome microarray analysis to compare the immune responses induced in murine bone marrow-derived macrophages (BMDMs) stimulated with L. acidophilus, H. pylori, or both bacteria in combination. While L. acidophilus induced a Th1-polarizing response characterized by high expression of interferon beta (IFN-β) and interleukin 12 (IL-12), H. pylori strongly induced the innate cytokines IL-1β and IL-1α. In BMDMs prestimulated with L. acidophilus, H. pylori blocked the expression of L. acidophilus-induced IFN-β and IL-12 and suppressed the expression of key regulators of the Rho, Rac, and Cdc42 GTPases. The inhibition of L. acidophilus-induced IFN-β was independent of H. pylori viability and the virulence factor CagPAI; however, a vacuolating cytotoxin (vacA) mutant was unable to block IFN-β. Confocal microscopy demonstrated that the addition of H. pylori to L. acidophilus-stimulated BMDMs redirects intracellular processing, leading to an accumulation of L. acidophilus in the endosomal and lysosomal compartments. Thus, our findings indicate that H. pylori inhibits the development of a strong Th1-polarizing response in BMDMs stimulated with L. acidophilus by blocking the production of IFN-β in a VacA-dependent manner. We suggest that this abrogation is caused by a redirection of the endocytotic pathway in the processing of L. acidophilus.",2013 Jun 11,"['Weiss, Gudrun', 'Forster, Sam', 'Irving, Aaron', 'Tate, Michelle', 'Ferrero, Richard L.', 'Hertzog, Paul', 'Frøkiær, Hanne', 'Kaparakis-Liaskos, Maria']",mBio,,,True
9b00534a32725e99d321aab3c6aeca97b3682904,PMC,Helicobacter pylori VacA Suppresses Lactobacillus acidophilus-Induced Interferon Beta Signaling in Macrophages via Alterations in the Endocytic Pathway,http://dx.doi.org/10.1128/mBio.00609-12,PMC3685213,23760466,CC BY-NC-SA,"Helicobacter pylori causes chronic gastritis and avoids elimination by the immune system of the infected host. The commensal bacterium Lactobacillus acidophilus has been suggested to exert beneficial effects as a supplement during H. pylori eradication therapy. In the present study, we applied whole-genome microarray analysis to compare the immune responses induced in murine bone marrow-derived macrophages (BMDMs) stimulated with L. acidophilus, H. pylori, or both bacteria in combination. While L. acidophilus induced a Th1-polarizing response characterized by high expression of interferon beta (IFN-β) and interleukin 12 (IL-12), H. pylori strongly induced the innate cytokines IL-1β and IL-1α. In BMDMs prestimulated with L. acidophilus, H. pylori blocked the expression of L. acidophilus-induced IFN-β and IL-12 and suppressed the expression of key regulators of the Rho, Rac, and Cdc42 GTPases. The inhibition of L. acidophilus-induced IFN-β was independent of H. pylori viability and the virulence factor CagPAI; however, a vacuolating cytotoxin (vacA) mutant was unable to block IFN-β. Confocal microscopy demonstrated that the addition of H. pylori to L. acidophilus-stimulated BMDMs redirects intracellular processing, leading to an accumulation of L. acidophilus in the endosomal and lysosomal compartments. Thus, our findings indicate that H. pylori inhibits the development of a strong Th1-polarizing response in BMDMs stimulated with L. acidophilus by blocking the production of IFN-β in a VacA-dependent manner. We suggest that this abrogation is caused by a redirection of the endocytotic pathway in the processing of L. acidophilus.",2013 Jun 11,"['Weiss, Gudrun', 'Forster, Sam', 'Irving, Aaron', 'Tate, Michelle', 'Ferrero, Richard L.', 'Hertzog, Paul', 'Frøkiær, Hanne', 'Kaparakis-Liaskos, Maria']",mBio,,,False
47ceb56d266552a6cc6c3c0eb153bab3b99a1e98,PMC,A Literature Review and Survey of Childhood Pneumonia Etiology Studies: 2000–2010,http://dx.doi.org/10.1093/cid/cir1053,PMC3693495,22403223,CC BY-NC-ND,"The Pneumonia Etiology Research for Child Health (PERCH) project is the largest multicountry etiology study of childhood pneumonia since the Board on Science and Technology in International Development studies of the 1980s. However, it is not the only recent or ongoing pneumonia etiology study, and even with seven sites, it cannot capture all epidemiologic settings in the developing world. Funding providers, researchers and policymakers rely on the best available evidence to strategically plan programs, new research directions and interventions. We aimed to describe the current landscape of recent pneumonia etiology studies in children under 5 years of age in the developed and developing world, as ascertained by a literature review of relevant studies with data since the year 2000 and a survey of researchers in the field of childhood pneumonia. We collected information on the study population, study design, case definitions, laboratory samples and methods and identified pathogens. A literature review identified 88 studies with child pneumonia etiology results. As of June 2010, our survey of researchers identified an additional 65 ongoing and recently completed child pneumonia etiology studies. This demonstrates the broad existing context into which the PERCH study must be placed. However, the landscape analysis also reveals a multiplicity of case definitions, levels of clinician involvement, facility types, specimen collection, and laboratory techniques. It reinforces the need for the standardization of methods and analyses for present and future pneumonia etiology studies in order to optimize their cumulative potential to accurately describe the microbial causes of childhood pneumonia.",2012 Apr 1,"['Gilani, Zunera', 'Kwong, Yuenting D.', 'Levine, Orin S.', 'Deloria-Knoll, Maria', 'Scott, J. Anthony G.', 'O’Brien, Katherine L.', 'Feikin, Daniel R.']",Clin Infect Dis,,,True
72bf8d8fff5a84e84e219df26f0d4cbdfa0bb15c,PMC,Antiviral effect of dietary germanium biotite supplementation in pigs experimentally infected with porcine reproductive and respiratory syndrome virus,http://dx.doi.org/10.4142/jvs.2013.14.2.135,PMC3694184,23814470,CC BY-NC,"Germanium biotite (GB) is an aluminosilicate mineral containing 36 ppm germanium. The present study was conducted to better understand the effects of GB on immune responses in a mouse model, and to demonstrate the clearance effects of this mineral against Porcine reproductive and respiratory syndrome virus (PRRSV) in experimentally infected pigs as an initial step towards the development of a feed supplement that would promote immune activity and help prevent diseases. In the mouse model, dietary supplementation with GB enhanced concanavalin A (ConA)-induced lymphocyte proliferation and increased the percentage of CD3+CD8+ T lymphocytes. In pigs experimentally infected with PRRSV, viral titers in lungs and lymphoid tissues from the GB-fed group were significantly decreased compared to those of the control group 12 days post-infection. Corresponding histopathological analyses demonstrated that GB-fed pigs displayed less severe pathological changes associated with PRRSV infection compared to the control group, indicating that GB promotes PRRSV clearance. These antiviral effects in pigs may be related to the ability of GB to increase CD3+CD8+ T lymphocyte production observed in the mice. Hence, this mineral may be an effective feed supplement for increasing immune activity and preventing disease.",2013 Jun 21,"['Jung, Bock-Gie', 'Lee, Jin-A', 'Lee, Bong-Joo']",J Vet Sci,,,True
58ef15f083c00ee3ae8e604a9c6e258576b7c7af,PMC,Multitask learning for host–pathogen protein interactions,http://dx.doi.org/10.1093/bioinformatics/btt245,PMC3694681,23812987,CC BY-NC,"Motivation: An important aspect of infectious disease research involves understanding the differences and commonalities in the infection mechanisms underlying various diseases. Systems biology-based approaches study infectious diseases by analyzing the interactions between the host species and the pathogen organisms. This work aims to combine the knowledge from experimental studies of host–pathogen interactions in several diseases to build stronger predictive models. Our approach is based on a formalism from machine learning called ‘multitask learning’, which considers the problem of building models across tasks that are related to each other. A ‘task’ in our scenario is the set of host–pathogen protein interactions involved in one disease. To integrate interactions from several tasks (i.e. diseases), our method exploits the similarity in the infection process across the diseases. In particular, we use the biological hypothesis that similar pathogens target the same critical biological processes in the host, in defining a common structure across the tasks. Results: Our current work on host–pathogen protein interaction prediction focuses on human as the host, and four bacterial species as pathogens. The multitask learning technique we develop uses a task-based regularization approach. We find that the resulting optimization problem is a difference of convex (DC) functions. To optimize, we implement a Convex–Concave procedure-based algorithm. We compare our integrative approach to baseline methods that build models on a single host–pathogen protein interaction dataset. Our results show that our approach outperforms the baselines on the training data. We further analyze the protein interaction predictions generated by the models, and find some interesting insights. Availability: The predictions and code are available at: http://www.cs.cmu.edu/∼mkshirsa/ismb2013_paper320.html Contact: j.klein-seetharaman@warwick.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.",2013 Jul 1,"['Kshirsagar, Meghana', 'Carbonell, Jaime', 'Klein-Seetharaman, Judith']",Bioinformatics,,,True
e30ed4938187ce36364831f6854629999c57cb68,PMC,Multitask learning for host–pathogen protein interactions,http://dx.doi.org/10.1093/bioinformatics/btt245,PMC3694681,23812987,CC BY-NC,"Motivation: An important aspect of infectious disease research involves understanding the differences and commonalities in the infection mechanisms underlying various diseases. Systems biology-based approaches study infectious diseases by analyzing the interactions between the host species and the pathogen organisms. This work aims to combine the knowledge from experimental studies of host–pathogen interactions in several diseases to build stronger predictive models. Our approach is based on a formalism from machine learning called ‘multitask learning’, which considers the problem of building models across tasks that are related to each other. A ‘task’ in our scenario is the set of host–pathogen protein interactions involved in one disease. To integrate interactions from several tasks (i.e. diseases), our method exploits the similarity in the infection process across the diseases. In particular, we use the biological hypothesis that similar pathogens target the same critical biological processes in the host, in defining a common structure across the tasks. Results: Our current work on host–pathogen protein interaction prediction focuses on human as the host, and four bacterial species as pathogens. The multitask learning technique we develop uses a task-based regularization approach. We find that the resulting optimization problem is a difference of convex (DC) functions. To optimize, we implement a Convex–Concave procedure-based algorithm. We compare our integrative approach to baseline methods that build models on a single host–pathogen protein interaction dataset. Our results show that our approach outperforms the baselines on the training data. We further analyze the protein interaction predictions generated by the models, and find some interesting insights. Availability: The predictions and code are available at: http://www.cs.cmu.edu/∼mkshirsa/ismb2013_paper320.html Contact: j.klein-seetharaman@warwick.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.",2013 Jul 1,"['Kshirsagar, Meghana', 'Carbonell, Jaime', 'Klein-Seetharaman, Judith']",Bioinformatics,,,False
3d4c571fcd1ba20b5c25488e82ced70014652cd4,PMC,Severe fever with thrombocytopenia syndrome virus expands its borders,http://dx.doi.org/10.1038/emi.2013.36,PMC3697302,26038472,CC BY-NC-ND,,2013 Jun 19,"['Wu, Ying', 'Gao, George F']",Emerg Microbes Infect,,,True
0e78935692851b0466f5a9234adb024e7735c8a3,PMC,Perspectives of public health laboratories in emerging infectious diseases,http://dx.doi.org/10.1038/emi.2013.34,PMC3697305,26038473,CC BY-NC-ND,"The world has experienced an increased incidence and transboundary spread of emerging infectious diseases over the last four decades. We divided emerging infectious diseases into four categories, with subcategories in categories 1 and 4. The categorization was based on the nature and characteristics of pathogens or infectious agents causing the emerging infections, which are directly related to the mechanisms and patterns of infectious disease emergence. The factors or combinations of factors contributing to the emergence of these pathogens vary within each category. We also classified public health laboratories into three types based on function, namely, research, reference and analytical diagnostic laboratories, with the last category being subclassified into primary (community-based) public health and clinical (medical) analytical diagnostic laboratories. The frontline/leading and/or supportive roles to be adopted by each type of public health laboratory for optimal performance to establish the correct etiological agents causing the diseases or outbreaks vary with respect to each category of emerging infectious diseases. We emphasize the need, especially for an outbreak investigation, to establish a harmonized and coordinated national public health laboratory system that integrates different categories of public health laboratories within a country and that is closely linked to the national public health delivery system and regional and international high-end laboratories.",2013 Jun 26,"['Chua, Kaw Bing', 'Gubler, Duane J']",Emerg Microbes Infect,,,True
7b1dd68a2de5fb4b3902e834ecc2fb6bd12f28f2,PMC,"Dual role of chloroquine in liver ischemia reperfusion injury: reduction of liver damage in early phase, but aggravation in late phase",http://dx.doi.org/10.1038/cddis.2013.225,PMC3702304,23807223,CC BY-NC-ND,"The anti-malaria drug chloroquine is well known as autophagy inhibitor. Chloroquine has also been used as anti-inflammatory drugs to treat inflammatory diseases. We hypothesized that chloroquine could have a dual effect in liver ischemia/reperfusion (I/R) injury: chloroquine on the one hand could protect the liver against I/R injury via inhibition of inflammatory response, but on the other hand could aggravate liver I/R injury through inhibition of autophagy. Rats (n=6 per group) were pre-treated with chloroquine (60 mg/kg, i.p.) 1 h before warm ischemia, and they were continuously subjected to a daily chloroquine injection for up to 2 days. Rats were killed 0.5, 6, 24 and 48 h after reperfusion. At the early phase (i.e., 0–6 h after reperfusion), chloroquine treatment ameliorated liver I/R injury, as indicated by lower serum aminotransferase levels, lower hepatic inflammatory cytokines and fewer histopathologic changes. In contrast, chloroquine worsened liver injury at the late phase of reperfusion (i.e., 24–48 h after reperfusion). The mechanism of protective action of chloroquine appeared to involve its ability to modulate mitogen-activated protein kinase activation, reduce high-mobility group box 1 release and inflammatory cytokines production, whereas chloroquine worsened liver injury via inhibition of autophagy and induction of hepatic apoptosis at the late phase. In conclusion, chloroquine prevents ischemic liver damage at the early phase, but aggravates liver damage at the late phase in liver I/R injury. This dual role of chloroquine should be considered when using chloroquine as an inhibitor of inflammation or autophagy in I/R injury.",2013 Jun 27,"['Fang, H', 'Liu, A', 'Dahmen, U', 'Dirsch, O']",Cell Death Dis,,,True
24709e4ba406a998d011ea9b31d33279bbabedb5,PMC,Picornavirus uncoating intermediate captured in atomic detail,http://dx.doi.org/10.1038/ncomms2889,PMC3709478,23728514,CC BY-NC-ND,"It remains largely mysterious how the genomes of non-enveloped eukaryotic viruses are transferred across a membrane into the host cell. Picornaviruses are simple models for such viruses, and initiate this uncoating process through particle expansion, which reveals channels through which internal capsid proteins and the viral genome presumably exit the particle, although this has not been clearly seen until now. Here we present the atomic structure of an uncoating intermediate for the major human picornavirus pathogen CAV16, which reveals VP1 partly extruded from the capsid, poised to embed in the host membrane. Together with previous low-resolution results, we are able to propose a detailed hypothesis for the ordered egress of the internal proteins, using two distinct sets of channels through the capsid, and suggest a structural link to the condensed RNA within the particle, which may be involved in triggering RNA release.",2013 Jun 3,"['Ren, Jingshan', 'Wang, Xiangxi', 'Hu, Zhongyu', 'Gao, Qiang', 'Sun, Yao', 'Li, Xuemei', 'Porta, Claudine', 'Walter, Thomas S.', 'Gilbert, Robert J.', 'Zhao, Yuguang', 'Axford, Danny', 'Williams, Mark', 'McAuley, Katherine', 'Rowlands, David J.', 'Yin, Weidong', 'Wang, Junzhi', 'Stuart, David I.', 'Rao, Zihe', 'Fry, Elizabeth E.']",Nat Commun,,,True
d8fafccc9ce11f09e43780f5ce9311095fa897c0,PMC,Picornavirus uncoating intermediate captured in atomic detail,http://dx.doi.org/10.1038/ncomms2889,PMC3709478,23728514,CC BY-NC-ND,"It remains largely mysterious how the genomes of non-enveloped eukaryotic viruses are transferred across a membrane into the host cell. Picornaviruses are simple models for such viruses, and initiate this uncoating process through particle expansion, which reveals channels through which internal capsid proteins and the viral genome presumably exit the particle, although this has not been clearly seen until now. Here we present the atomic structure of an uncoating intermediate for the major human picornavirus pathogen CAV16, which reveals VP1 partly extruded from the capsid, poised to embed in the host membrane. Together with previous low-resolution results, we are able to propose a detailed hypothesis for the ordered egress of the internal proteins, using two distinct sets of channels through the capsid, and suggest a structural link to the condensed RNA within the particle, which may be involved in triggering RNA release.",2013 Jun 3,"['Ren, Jingshan', 'Wang, Xiangxi', 'Hu, Zhongyu', 'Gao, Qiang', 'Sun, Yao', 'Li, Xuemei', 'Porta, Claudine', 'Walter, Thomas S.', 'Gilbert, Robert J.', 'Zhao, Yuguang', 'Axford, Danny', 'Williams, Mark', 'McAuley, Katherine', 'Rowlands, David J.', 'Yin, Weidong', 'Wang, Junzhi', 'Stuart, David I.', 'Rao, Zihe', 'Fry, Elizabeth E.']",Nat Commun,,,True
9cc0534fb1e5181fa20aa2891f5614deab6b87f8,PMC,Mathematical modeling of infectious disease dynamics,http://dx.doi.org/10.4161/viru.24041,PMC3710332,23552814,CC BY-NC,"Over the last years, an intensive worldwide effort is speeding up the developments in the establishment of a global surveillance network for combating pandemics of emergent and re-emergent infectious diseases. Scientists from different fields extending from medicine and molecular biology to computer science and applied mathematics have teamed up for rapid assessment of potentially urgent situations. Toward this aim mathematical modeling plays an important role in efforts that focus on predicting, assessing, and controlling potential outbreaks. To better understand and model the contagious dynamics the impact of numerous variables ranging from the micro host–pathogen level to host-to-host interactions, as well as prevailing ecological, social, economic, and demographic factors across the globe have to be analyzed and thoroughly studied. Here, we present and discuss the main approaches that are used for the surveillance and modeling of infectious disease dynamics. We present the basic concepts underpinning their implementation and practice and for each category we give an annotated list of representative works.",2013 May 15,"['Siettos, Constantinos I.', 'Russo, Lucia']",Virulence,,,True
6e33bf088cfbcde318f35f3be8dea6810b0b96ce,PMC,Does spatial proximity drive norovirus transmission during outbreaks in hospitals?,http://dx.doi.org/10.1136/bmjopen-2013-003060,PMC3710976,23852138,CC BY-NC,"OBJECTIVE: To assess the role of spatial proximity, defined as patients sharing bays, in the spread of norovirus during outbreaks in hospitals. DESIGN: Enhanced surveillance of norovirus outbreaks between November 2009 and November 2011. METHODS: Data were gathered during 149 outbreaks of norovirus in hospital wards from five hospitals in two major cities in England serving a population of two million. We used the time between the first two cases of each outbreak to estimate the serial interval for norovirus in this setting. This distribution and dates of illness onset were used to calculate epidemic trees for each outbreak. We then used a permutation test to assess whether proximity, for all outbreaks, was more extreme than would be expected by chance under the null hypothesis that proximity was not associated with transmission risk. RESULTS: 65 outbreaks contained complete data on both onset dates and ward position. We estimated the serial interval to be 1.86 days (95% CI 1.6 to 2.2 days), and with this value found strong evidence to reject the null hypothesis that proximity was not significant (p<0.001). Sensitivity analysis using different values of the serial interval showed that there was evidence to reject the null hypothesis provided the assumed serial interval was less than 2.5 days. CONCLUSIONS: Our results provide evidence that patients occupying the same bay as patients with symptomatic norovirus infection are at an increased risk of becoming infected by these patients compared with patients elsewhere in the same ward.",2013 Jul 12,"['Harris, John P', 'Lopman, Ben A', 'Cooper, Ben S', ""O'Brien, Sarah J""]",BMJ Open,,,True
efcd4f058d2b435a17c63793904cbf85c899b982,PMC,Does spatial proximity drive norovirus transmission during outbreaks in hospitals?,http://dx.doi.org/10.1136/bmjopen-2013-003060,PMC3710976,23852138,CC BY-NC,"OBJECTIVE: To assess the role of spatial proximity, defined as patients sharing bays, in the spread of norovirus during outbreaks in hospitals. DESIGN: Enhanced surveillance of norovirus outbreaks between November 2009 and November 2011. METHODS: Data were gathered during 149 outbreaks of norovirus in hospital wards from five hospitals in two major cities in England serving a population of two million. We used the time between the first two cases of each outbreak to estimate the serial interval for norovirus in this setting. This distribution and dates of illness onset were used to calculate epidemic trees for each outbreak. We then used a permutation test to assess whether proximity, for all outbreaks, was more extreme than would be expected by chance under the null hypothesis that proximity was not associated with transmission risk. RESULTS: 65 outbreaks contained complete data on both onset dates and ward position. We estimated the serial interval to be 1.86 days (95% CI 1.6 to 2.2 days), and with this value found strong evidence to reject the null hypothesis that proximity was not significant (p<0.001). Sensitivity analysis using different values of the serial interval showed that there was evidence to reject the null hypothesis provided the assumed serial interval was less than 2.5 days. CONCLUSIONS: Our results provide evidence that patients occupying the same bay as patients with symptomatic norovirus infection are at an increased risk of becoming infected by these patients compared with patients elsewhere in the same ward.",2013 Jul 12,"['Harris, John P', 'Lopman, Ben A', 'Cooper, Ben S', ""O'Brien, Sarah J""]",BMJ Open,,,True
8110f20d92488d80baabe4213e6ce57ec9d58e7d,PMC,Does spatial proximity drive norovirus transmission during outbreaks in hospitals?,http://dx.doi.org/10.1136/bmjopen-2013-003060,PMC3710976,23852138,CC BY-NC,"OBJECTIVE: To assess the role of spatial proximity, defined as patients sharing bays, in the spread of norovirus during outbreaks in hospitals. DESIGN: Enhanced surveillance of norovirus outbreaks between November 2009 and November 2011. METHODS: Data were gathered during 149 outbreaks of norovirus in hospital wards from five hospitals in two major cities in England serving a population of two million. We used the time between the first two cases of each outbreak to estimate the serial interval for norovirus in this setting. This distribution and dates of illness onset were used to calculate epidemic trees for each outbreak. We then used a permutation test to assess whether proximity, for all outbreaks, was more extreme than would be expected by chance under the null hypothesis that proximity was not associated with transmission risk. RESULTS: 65 outbreaks contained complete data on both onset dates and ward position. We estimated the serial interval to be 1.86 days (95% CI 1.6 to 2.2 days), and with this value found strong evidence to reject the null hypothesis that proximity was not significant (p<0.001). Sensitivity analysis using different values of the serial interval showed that there was evidence to reject the null hypothesis provided the assumed serial interval was less than 2.5 days. CONCLUSIONS: Our results provide evidence that patients occupying the same bay as patients with symptomatic norovirus infection are at an increased risk of becoming infected by these patients compared with patients elsewhere in the same ward.",2013 Jul 12,"['Harris, John P', 'Lopman, Ben A', 'Cooper, Ben S', ""O'Brien, Sarah J""]",BMJ Open,,,False
db633ad6a8771828545a8f3d7419722897c4fa9f,PMC,Sublingual Delivery of Vaccines for the Induction of Mucosal Immunity,http://dx.doi.org/10.4110/in.2013.13.3.81,PMC3718922,23885221,CC BY-NC,"The mucosal surfaces are constantly exposed to incoming pathogens which can cause infections that result in severe morbidity and/or mortality. Studies have reported that mucosal immunity is important for providing protection against these pathogens and that mucosal vaccination is effective in preventing local infections. For many years, the sublingual mucosa has been targeted to deliver immunotherapy to treat allergic hypersensitivities. However, the potential of vaccine delivery via sublingual mucosal has received little attention until recently. Recent studies exploring such potential have documented the safety and effectiveness of sublingual immunization, demonstrating the ability of sublingual immunization to induce both systemic and mucosal immune responses against a variety of antigens, including soluble proteins, inter particulate antigens, and live-attenuated viruses. This review will summarize the recent findings that address the promising potential of sublingual immunization in proving protection against various mucosal pathogens.",2013 Jun 30,"['Shim, Byoung-Shik', 'Choi, Youngjoo', 'Cheon, In Su', 'Song, Man Ki']",Immune Netw,,,True
56ac158658a5eb9ee2efbc07d6ec1474417fe8ba,PMC,Potential implication of new torque teno mini viruses in parapneumonic empyema in children,http://dx.doi.org/10.1183/09031936.00107212,PMC3729974,23060626,CC BY-NC,"An unexplained increase in the incidence of parapneumonic empyema (PPE) in pneumonia cases has been reported in recent years. The present study investigated the genetic and biological specifications of new isolates of torque teno mini virus (TTMV) detected in pleural effusion samples from children hospitalised for severe pneumonia with PPE. A pathogen discovery protocol was applied in undiagnosed pleural effusion samples and led to the identification of three new isolates of TTMV (TTMV-LY). Isolated TTMV-LY genomes were transfected into A549 and human embryonic kidney 293T cells and viral replication was assessed by quantitative real-time PCR and full-length genome amplification. A549 cells were further infected with released TTMV-LY virions and the induced-innate immune response was measured by multiplex immunoassays. Genetic analyses of the three TTMV-LY genomes revealed a classic genomic organisation but a weak identity (<64%) with known sequences. We demonstrated the in vitro replication of TTMV-LY in alveolar epithelial cells and the effective release of infectious viral particles. We also showed a selective production of inflammatory mediators in response to TTMV infection. This study reports the description of replicative TTMV-LY isolated from parapneumonic effusions of children hospitalised with PPE, suggesting a potential role of the virus in the pathogenesis of pneumonia.",2013 Aug 11,"['Galmès, Johanna', 'Li, Yongjun', 'Rajoharison, Alain', 'Ren, Lili', 'Dollet, Sandra', 'Richard, Nathalie', 'Vernet, Guy', 'Javouhey, Etienne', 'Wang, Jianwei', 'Telles, Jean-Noël', 'Paranhos-Baccalà, Gláucia']",Eur Respir J,,,True
5ab1eceaa469bc34270595cb9b5ea00e6ed3fe71,PMC,Potential implication of new torque teno mini viruses in parapneumonic empyema in children,http://dx.doi.org/10.1183/09031936.00107212,PMC3729974,23060626,CC BY-NC,"An unexplained increase in the incidence of parapneumonic empyema (PPE) in pneumonia cases has been reported in recent years. The present study investigated the genetic and biological specifications of new isolates of torque teno mini virus (TTMV) detected in pleural effusion samples from children hospitalised for severe pneumonia with PPE. A pathogen discovery protocol was applied in undiagnosed pleural effusion samples and led to the identification of three new isolates of TTMV (TTMV-LY). Isolated TTMV-LY genomes were transfected into A549 and human embryonic kidney 293T cells and viral replication was assessed by quantitative real-time PCR and full-length genome amplification. A549 cells were further infected with released TTMV-LY virions and the induced-innate immune response was measured by multiplex immunoassays. Genetic analyses of the three TTMV-LY genomes revealed a classic genomic organisation but a weak identity (<64%) with known sequences. We demonstrated the in vitro replication of TTMV-LY in alveolar epithelial cells and the effective release of infectious viral particles. We also showed a selective production of inflammatory mediators in response to TTMV infection. This study reports the description of replicative TTMV-LY isolated from parapneumonic effusions of children hospitalised with PPE, suggesting a potential role of the virus in the pathogenesis of pneumonia.",2013 Aug 11,"['Galmès, Johanna', 'Li, Yongjun', 'Rajoharison, Alain', 'Ren, Lili', 'Dollet, Sandra', 'Richard, Nathalie', 'Vernet, Guy', 'Javouhey, Etienne', 'Wang, Jianwei', 'Telles, Jean-Noël', 'Paranhos-Baccalà, Gláucia']",Eur Respir J,,,False
43eb920135bc1acb5cb4f1d91b5d06079c53765b,PMC,Anticancer compound ABT-263 accelerates apoptosis in virus-infected cells and imbalances cytokine production and lowers survival rates of infected mice,http://dx.doi.org/10.1038/cddis.2013.267,PMC3730437,23887633,CC BY-NC-SA,"ABT-263 and its structural analogues ABT-199 and ABT-737 inhibit B-cell lymphoma 2 (Bcl-2), BCL2L1 long isoform (Bcl-xL) and BCL2L2 (Bcl-w) proteins and promote cancer cell death. Here, we show that at non-cytotoxic concentrations, these small molecules accelerate the deaths of non-cancerous cells infected with influenza A virus (IAV) or other viruses. In particular, we demonstrate that ABT-263 altered Bcl-xL interactions with Bcl-2 antagonist of cell death (Bad), Bcl-2-associated X protein (Bax), uveal autoantigen with coiled-coil domains and ankyrin repeats protein (UACA). ABT-263 thereby activated the caspase-9-mediated mitochondria-initiated apoptosis pathway, which, together with the IAV-initiated caspase-8-mediated apoptosis pathway, triggered the deaths of IAV-infected cells. Our results also indicate that Bcl-xL, Bcl-2 and Bcl-w interact with pattern recognition receptors (PRRs) that sense virus constituents to regulate cellular apoptosis. Importantly, premature killing of IAV-infected cells by ABT-263 attenuated the production of key pro-inflammatory and antiviral cytokines. The imbalance in cytokine production was also observed in ABT-263-treated IAV-infected mice, which resulted in an inability of the immune system to clear the virus and eventually lowered the survival rates of infected animals. Thus, the results suggest that the chemical inhibition of Bcl-xL, Bcl-2 and Bcl-w could potentially be hazardous for cancer patients with viral infections.",2013 Jul 25,"['Kakkola, L', 'Denisova, O V', 'Tynell, J', 'Viiliäinen, J', 'Ysenbaert, T', 'Matos, R C', 'Nagaraj, A', 'Öhman, T', 'Kuivanen, S', 'Paavilainen, H', 'Feng, L', 'Yadav, B', 'Julkunen, I', 'Vapalahti, O', 'Hukkanen, V', 'Stenman, J', 'Aittokallio, T', 'Verschuren, E W', 'Ojala, P M', 'Nyman, T', 'Saelens, X', 'Dzeyk, K', 'Kainov, D E']",Cell Death Dis,,,True
e37d98d6e6ded2f9207ad1c965245e6562e5a5b2,PMC,Anticancer compound ABT-263 accelerates apoptosis in virus-infected cells and imbalances cytokine production and lowers survival rates of infected mice,http://dx.doi.org/10.1038/cddis.2013.267,PMC3730437,23887633,CC BY-NC-SA,"ABT-263 and its structural analogues ABT-199 and ABT-737 inhibit B-cell lymphoma 2 (Bcl-2), BCL2L1 long isoform (Bcl-xL) and BCL2L2 (Bcl-w) proteins and promote cancer cell death. Here, we show that at non-cytotoxic concentrations, these small molecules accelerate the deaths of non-cancerous cells infected with influenza A virus (IAV) or other viruses. In particular, we demonstrate that ABT-263 altered Bcl-xL interactions with Bcl-2 antagonist of cell death (Bad), Bcl-2-associated X protein (Bax), uveal autoantigen with coiled-coil domains and ankyrin repeats protein (UACA). ABT-263 thereby activated the caspase-9-mediated mitochondria-initiated apoptosis pathway, which, together with the IAV-initiated caspase-8-mediated apoptosis pathway, triggered the deaths of IAV-infected cells. Our results also indicate that Bcl-xL, Bcl-2 and Bcl-w interact with pattern recognition receptors (PRRs) that sense virus constituents to regulate cellular apoptosis. Importantly, premature killing of IAV-infected cells by ABT-263 attenuated the production of key pro-inflammatory and antiviral cytokines. The imbalance in cytokine production was also observed in ABT-263-treated IAV-infected mice, which resulted in an inability of the immune system to clear the virus and eventually lowered the survival rates of infected animals. Thus, the results suggest that the chemical inhibition of Bcl-xL, Bcl-2 and Bcl-w could potentially be hazardous for cancer patients with viral infections.",2013 Jul 25,"['Kakkola, L', 'Denisova, O V', 'Tynell, J', 'Viiliäinen, J', 'Ysenbaert, T', 'Matos, R C', 'Nagaraj, A', 'Öhman, T', 'Kuivanen, S', 'Paavilainen, H', 'Feng, L', 'Yadav, B', 'Julkunen, I', 'Vapalahti, O', 'Hukkanen, V', 'Stenman, J', 'Aittokallio, T', 'Verschuren, E W', 'Ojala, P M', 'Nyman, T', 'Saelens, X', 'Dzeyk, K', 'Kainov, D E']",Cell Death Dis,,,False
18d7f4c8e204349b39a037c19874cff1b34d0f97,PMC,Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4,http://dx.doi.org/10.1038/cr.2013.92,PMC3731569,23835475,CC BY-NC-ND,"The spike glycoprotein (S) of recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) targets the cellular receptor, dipeptidyl peptidase 4 (DPP4). Sequence comparison and modeling analysis have revealed a putative receptor-binding domain (RBD) on the viral spike, which mediates this interaction. We report the 3.0 Å-resolution crystal structure of MERS-CoV RBD bound to the extracellular domain of human DPP4. Our results show that MERS-CoV RBD consists of a core and a receptor-binding subdomain. The receptor-binding subdomain interacts with DPP4 β-propeller but not its intrinsic hydrolase domain. MERS-CoV RBD and related SARS-CoV RBD share a high degree of structural similarity in their core subdomains, but are notably divergent in the receptor-binding subdomain. Mutagenesis studies have identified several key residues in the receptor-binding subdomain that are critical for viral binding to DPP4 and entry into the target cell. The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS-CoV infection.",2013 Aug 9,"['Wang, Nianshuang', 'Shi, Xuanling', 'Jiang, Liwei', 'Zhang, Senyan', 'Wang, Dongli', 'Tong, Pei', 'Guo, Dongxing', 'Fu, Lili', 'Cui, Ye', 'Liu, Xi', 'Arledge, Kelly C', 'Chen, Ying-Hua', 'Zhang, Linqi', 'Wang, Xinquan']",Cell Res,,,True
67aa24cc6dc0fef3ffbff18a9e6a4c47bbdcd03f,PMC,Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4,http://dx.doi.org/10.1038/cr.2013.92,PMC3731569,23835475,CC BY-NC-ND,"The spike glycoprotein (S) of recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) targets the cellular receptor, dipeptidyl peptidase 4 (DPP4). Sequence comparison and modeling analysis have revealed a putative receptor-binding domain (RBD) on the viral spike, which mediates this interaction. We report the 3.0 Å-resolution crystal structure of MERS-CoV RBD bound to the extracellular domain of human DPP4. Our results show that MERS-CoV RBD consists of a core and a receptor-binding subdomain. The receptor-binding subdomain interacts with DPP4 β-propeller but not its intrinsic hydrolase domain. MERS-CoV RBD and related SARS-CoV RBD share a high degree of structural similarity in their core subdomains, but are notably divergent in the receptor-binding subdomain. Mutagenesis studies have identified several key residues in the receptor-binding subdomain that are critical for viral binding to DPP4 and entry into the target cell. The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS-CoV infection.",2013 Aug 9,"['Wang, Nianshuang', 'Shi, Xuanling', 'Jiang, Liwei', 'Zhang, Senyan', 'Wang, Dongli', 'Tong, Pei', 'Guo, Dongxing', 'Fu, Lili', 'Cui, Ye', 'Liu, Xi', 'Arledge, Kelly C', 'Chen, Ying-Hua', 'Zhang, Linqi', 'Wang, Xinquan']",Cell Res,,,False
9fd3771535c3859f77fa86d03356ea68f5967618,PMC,Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4,http://dx.doi.org/10.1038/cr.2013.92,PMC3731569,23835475,CC BY-NC-ND,"The spike glycoprotein (S) of recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) targets the cellular receptor, dipeptidyl peptidase 4 (DPP4). Sequence comparison and modeling analysis have revealed a putative receptor-binding domain (RBD) on the viral spike, which mediates this interaction. We report the 3.0 Å-resolution crystal structure of MERS-CoV RBD bound to the extracellular domain of human DPP4. Our results show that MERS-CoV RBD consists of a core and a receptor-binding subdomain. The receptor-binding subdomain interacts with DPP4 β-propeller but not its intrinsic hydrolase domain. MERS-CoV RBD and related SARS-CoV RBD share a high degree of structural similarity in their core subdomains, but are notably divergent in the receptor-binding subdomain. Mutagenesis studies have identified several key residues in the receptor-binding subdomain that are critical for viral binding to DPP4 and entry into the target cell. The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS-CoV infection.",2013 Aug 9,"['Wang, Nianshuang', 'Shi, Xuanling', 'Jiang, Liwei', 'Zhang, Senyan', 'Wang, Dongli', 'Tong, Pei', 'Guo, Dongxing', 'Fu, Lili', 'Cui, Ye', 'Liu, Xi', 'Arledge, Kelly C', 'Chen, Ying-Hua', 'Zhang, Linqi', 'Wang, Xinquan']",Cell Res,,,False
2da9cfdbb5516e1cbe944ff6241e0de9a5850dd2,PMC,Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4,http://dx.doi.org/10.1038/cr.2013.92,PMC3731569,23835475,CC BY-NC-ND,"The spike glycoprotein (S) of recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) targets the cellular receptor, dipeptidyl peptidase 4 (DPP4). Sequence comparison and modeling analysis have revealed a putative receptor-binding domain (RBD) on the viral spike, which mediates this interaction. We report the 3.0 Å-resolution crystal structure of MERS-CoV RBD bound to the extracellular domain of human DPP4. Our results show that MERS-CoV RBD consists of a core and a receptor-binding subdomain. The receptor-binding subdomain interacts with DPP4 β-propeller but not its intrinsic hydrolase domain. MERS-CoV RBD and related SARS-CoV RBD share a high degree of structural similarity in their core subdomains, but are notably divergent in the receptor-binding subdomain. Mutagenesis studies have identified several key residues in the receptor-binding subdomain that are critical for viral binding to DPP4 and entry into the target cell. The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS-CoV infection.",2013 Aug 9,"['Wang, Nianshuang', 'Shi, Xuanling', 'Jiang, Liwei', 'Zhang, Senyan', 'Wang, Dongli', 'Tong, Pei', 'Guo, Dongxing', 'Fu, Lili', 'Cui, Ye', 'Liu, Xi', 'Arledge, Kelly C', 'Chen, Ying-Hua', 'Zhang, Linqi', 'Wang, Xinquan']",Cell Res,,,False
659aa7e94586eea37a764bec95aab720f2ab4450,PMC,Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4,http://dx.doi.org/10.1038/cr.2013.92,PMC3731569,23835475,CC BY-NC-ND,"The spike glycoprotein (S) of recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) targets the cellular receptor, dipeptidyl peptidase 4 (DPP4). Sequence comparison and modeling analysis have revealed a putative receptor-binding domain (RBD) on the viral spike, which mediates this interaction. We report the 3.0 Å-resolution crystal structure of MERS-CoV RBD bound to the extracellular domain of human DPP4. Our results show that MERS-CoV RBD consists of a core and a receptor-binding subdomain. The receptor-binding subdomain interacts with DPP4 β-propeller but not its intrinsic hydrolase domain. MERS-CoV RBD and related SARS-CoV RBD share a high degree of structural similarity in their core subdomains, but are notably divergent in the receptor-binding subdomain. Mutagenesis studies have identified several key residues in the receptor-binding subdomain that are critical for viral binding to DPP4 and entry into the target cell. The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS-CoV infection.",2013 Aug 9,"['Wang, Nianshuang', 'Shi, Xuanling', 'Jiang, Liwei', 'Zhang, Senyan', 'Wang, Dongli', 'Tong, Pei', 'Guo, Dongxing', 'Fu, Lili', 'Cui, Ye', 'Liu, Xi', 'Arledge, Kelly C', 'Chen, Ying-Hua', 'Zhang, Linqi', 'Wang, Xinquan']",Cell Res,,,False
37c2cf4cca296eee2cf3578b3b1ddeb6a0b415ed,PMC,Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4,http://dx.doi.org/10.1038/cr.2013.92,PMC3731569,23835475,CC BY-NC-ND,"The spike glycoprotein (S) of recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) targets the cellular receptor, dipeptidyl peptidase 4 (DPP4). Sequence comparison and modeling analysis have revealed a putative receptor-binding domain (RBD) on the viral spike, which mediates this interaction. We report the 3.0 Å-resolution crystal structure of MERS-CoV RBD bound to the extracellular domain of human DPP4. Our results show that MERS-CoV RBD consists of a core and a receptor-binding subdomain. The receptor-binding subdomain interacts with DPP4 β-propeller but not its intrinsic hydrolase domain. MERS-CoV RBD and related SARS-CoV RBD share a high degree of structural similarity in their core subdomains, but are notably divergent in the receptor-binding subdomain. Mutagenesis studies have identified several key residues in the receptor-binding subdomain that are critical for viral binding to DPP4 and entry into the target cell. The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS-CoV infection.",2013 Aug 9,"['Wang, Nianshuang', 'Shi, Xuanling', 'Jiang, Liwei', 'Zhang, Senyan', 'Wang, Dongli', 'Tong, Pei', 'Guo, Dongxing', 'Fu, Lili', 'Cui, Ye', 'Liu, Xi', 'Arledge, Kelly C', 'Chen, Ying-Hua', 'Zhang, Linqi', 'Wang, Xinquan']",Cell Res,,,False
51103aa53c031671ba7e27ce2b04dc645a47ce48,PMC,Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4,http://dx.doi.org/10.1038/cr.2013.92,PMC3731569,23835475,CC BY-NC-ND,"The spike glycoprotein (S) of recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) targets the cellular receptor, dipeptidyl peptidase 4 (DPP4). Sequence comparison and modeling analysis have revealed a putative receptor-binding domain (RBD) on the viral spike, which mediates this interaction. We report the 3.0 Å-resolution crystal structure of MERS-CoV RBD bound to the extracellular domain of human DPP4. Our results show that MERS-CoV RBD consists of a core and a receptor-binding subdomain. The receptor-binding subdomain interacts with DPP4 β-propeller but not its intrinsic hydrolase domain. MERS-CoV RBD and related SARS-CoV RBD share a high degree of structural similarity in their core subdomains, but are notably divergent in the receptor-binding subdomain. Mutagenesis studies have identified several key residues in the receptor-binding subdomain that are critical for viral binding to DPP4 and entry into the target cell. The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS-CoV infection.",2013 Aug 9,"['Wang, Nianshuang', 'Shi, Xuanling', 'Jiang, Liwei', 'Zhang, Senyan', 'Wang, Dongli', 'Tong, Pei', 'Guo, Dongxing', 'Fu, Lili', 'Cui, Ye', 'Liu, Xi', 'Arledge, Kelly C', 'Chen, Ying-Hua', 'Zhang, Linqi', 'Wang, Xinquan']",Cell Res,,,False
1a8aba4a689f85e64e636c41a55327aa82112b0e,PMC,Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4,http://dx.doi.org/10.1038/cr.2013.92,PMC3731569,23835475,CC BY-NC-ND,"The spike glycoprotein (S) of recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) targets the cellular receptor, dipeptidyl peptidase 4 (DPP4). Sequence comparison and modeling analysis have revealed a putative receptor-binding domain (RBD) on the viral spike, which mediates this interaction. We report the 3.0 Å-resolution crystal structure of MERS-CoV RBD bound to the extracellular domain of human DPP4. Our results show that MERS-CoV RBD consists of a core and a receptor-binding subdomain. The receptor-binding subdomain interacts with DPP4 β-propeller but not its intrinsic hydrolase domain. MERS-CoV RBD and related SARS-CoV RBD share a high degree of structural similarity in their core subdomains, but are notably divergent in the receptor-binding subdomain. Mutagenesis studies have identified several key residues in the receptor-binding subdomain that are critical for viral binding to DPP4 and entry into the target cell. The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS-CoV infection.",2013 Aug 9,"['Wang, Nianshuang', 'Shi, Xuanling', 'Jiang, Liwei', 'Zhang, Senyan', 'Wang, Dongli', 'Tong, Pei', 'Guo, Dongxing', 'Fu, Lili', 'Cui, Ye', 'Liu, Xi', 'Arledge, Kelly C', 'Chen, Ying-Hua', 'Zhang, Linqi', 'Wang, Xinquan']",Cell Res,,,False
b294375c51953d106bead1dd39809747c9f46466,PMC,Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury,http://dx.doi.org/10.1128/mBio.00271-13,PMC3747576,23919993,CC BY-NC-SA,"Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV.",2013 Aug 6,"['Gralinski, Lisa E.', 'Bankhead, Armand', 'Jeng, Sophia', 'Menachery, Vineet D.', 'Proll, Sean', 'Belisle, Sarah E.', 'Matzke, Melissa', 'Webb-Robertson, Bobbie-Jo M.', 'Luna, Maria L.', 'Shukla, Anil K.', 'Ferris, Martin T.', 'Bolles, Meagan', 'Chang, Jean', 'Aicher, Lauri', 'Waters, Katrina M.', 'Smith, Richard D.', 'Metz, Thomas O.', 'Law, G. Lynn', 'Katze, Michael G.', 'McWeeney, Shannon', 'Baric, Ralph S.']",mBio,,,True
8682e080613d625a9f6955e5eb0fe80bbbaefda9,PMC,"Severe Acute Respiratory Syndrome Coronavirus Nonstructural Proteins 3, 4, and 6 Induce Double-Membrane Vesicles",http://dx.doi.org/10.1128/mBio.00524-13,PMC3747587,23943763,CC BY-NC-SA,"Coronaviruses (CoV), like other positive-stranded RNA viruses, redirect and rearrange host cell membranes for use as part of the viral genome replication and transcription machinery. Specifically, coronaviruses induce the formation of double-membrane vesicles in infected cells. Although these double-membrane vesicles have been well characterized, the mechanism behind their formation remains unclear, including which viral proteins are responsible. Here, we use transfection of plasmid constructs encoding full-length versions of the three transmembrane-containing nonstructural proteins (nsps) of the severe acute respiratory syndrome (SARS) coronavirus to examine the ability of each to induce double-membrane vesicles in tissue culture. nsp3 has membrane disordering and proliferation ability, both in its full-length form and in a C-terminal-truncated form. nsp3 and nsp4 working together have the ability to pair membranes. nsp6 has membrane proliferation ability as well, inducing perinuclear vesicles localized around the microtubule organizing center. Together, nsp3, nsp4, and nsp6 have the ability to induce double-membrane vesicles that are similar to those observed in SARS coronavirus-infected cells. This activity appears to require the full-length form of nsp3 for action, as double-membrane vesicles were not seen in cells coexpressing the C-terminal truncation nsp3 with nsp4 and nsp6.",2013 Aug 13,"['Angelini, Megan M.', 'Akhlaghpour, Marzieh', 'Neuman, Benjamin W.', 'Buchmeier, Michael J.']",mBio,,,True
0fc5801b4cdc21c018c93aa3cbc9b601491fdeb4,PMC,The Middle East Respiratory Syndrome—How Worried Should We Be?,http://dx.doi.org/10.1128/mBio.00531-13,PMC3747588,23963179,CC BY-NC-SA,"Ten years after the severe acute respiratory syndrome epidemic, a second coronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV), has been identified as the cause of a highly lethal pneumonia in patients in the Middle East and in travelers from this region. Over the past 9 months, since the virus was first isolated, much has been learned about the biology of the virus. It is now clear that MERS-CoV is transmissible from person to person, and its close relationship with several bat coronaviruses suggests that these animals may be the ultimate source of the infection. However, many key issues need to be addressed, including identification of the proximate, presumably zoonotic, source of the infection, the prevalence of the infection in human populations, details regarding clinical and pathological features of the human infection, the establishment of a small rodent model for the infection, and the virological and immune basis for the severe disease observed in most patients. Most importantly, we do not know whether a MERS-CoV epidemic is likely or not. Infection with the virus has so far resulted in only 91 cases and 46 deaths (as of 29 July 2013), but it is nonetheless setting off alarm bells among public health officials, including Margaret Chan, Director-General of the World Health Organization, who called MERS-CoV “a threat to the entire world.” This article reviews some of the progress that has been made and discusses some of the questions that need to be answered.",2013 Aug 20,"Perlman, Stanley",mBio,,,True
f956e0b68eaf7bac8fa50f0d1a9859938a96f8ad,PMC,Prion Diseases as Transmissible Zoonotic Diseases,http://dx.doi.org/10.1016/j.phrp.2012.12.008,PMC3747681,24159531,CC BY-NC,"Prion diseases, also called transmissible spongiform encephalopathies (TSEs), lead to neurological dysfunction in animals and are fatal. Infectious prion proteins are causative agents of many mammalian TSEs, including scrapie (in sheep), chronic wasting disease (in deer and elk), bovine spongiform encephalopathy (BSE; in cattle), and Creutzfeldt–Jakob disease (CJD; in humans). BSE, better known as mad cow disease, is among the many recently discovered zoonotic diseases. BSE cases were first reported in the United Kingdom in 1986. Variant CJD (vCJD) is a disease that was first detected in 1996, which affects humans and is linked to the BSE epidemic in cattle. vCJD is presumed to be caused by consumption of contaminated meat and other food products derived from affected cattle. The BSE epidemic peaked in 1992 and decreased thereafter; this decline is continuing sharply owing to intensive surveillance and screening programs in the Western world. However, there are still new outbreaks and/or progression of prion diseases, including atypical BSE, and iatrogenic CJD and vCJD via organ transplantation and blood transfusion. This paper summarizes studies on prions, particularly on prion molecular mechanisms, BSE, vCJD, and diagnostic procedures. Risk perception and communication policies of the European Union for the prevention of prion diseases are also addressed to provide recommendations for appropriate government policies in Korea.",2013 Feb,"['Lee, Jeongmin', 'Kim, Su Yeon', 'Hwang, Kyu Jam', 'Ju, Young Ran', 'Woo, Hee-Jong']",Osong Public Health Res Perspect,,,True
634128ea7d7736750e1c3cd0a48bb37843d06dac,PMC,A Strategy To Estimate Unknown Viral Diversity in Mammals,http://dx.doi.org/10.1128/mBio.00598-13,PMC3760253,24003179,CC BY-NC-SA,"The majority of emerging zoonoses originate in wildlife, and many are caused by viruses. However, there are no rigorous estimates of total viral diversity (here termed “virodiversity”) for any wildlife species, despite the utility of this to future surveillance and control of emerging zoonoses. In this case study, we repeatedly sampled a mammalian wildlife host known to harbor emerging zoonotic pathogens (the Indian Flying Fox, Pteropus giganteus) and used PCR with degenerate viral family-level primers to discover and analyze the occurrence patterns of 55 viruses from nine viral families. We then adapted statistical techniques used to estimate biodiversity in vertebrates and plants and estimated the total viral richness of these nine families in P. giganteus to be 58 viruses. Our analyses demonstrate proof-of-concept of a strategy for estimating viral richness and provide the first statistically supported estimate of the number of undiscovered viruses in a mammalian host. We used a simple extrapolation to estimate that there are a minimum of 320,000 mammalian viruses awaiting discovery within these nine families, assuming all species harbor a similar number of viruses, with minimal turnover between host species. We estimate the cost of discovering these viruses to be ~$6.3 billion (or ~$1.4 billion for 85% of the total diversity), which if annualized over a 10-year study time frame would represent a small fraction of the cost of many pandemic zoonoses.",2013 Sep 3,"['Anthony, Simon J.', 'Epstein, Jonathan H.', 'Murray, Kris A.', 'Navarrete-Macias, Isamara', 'Zambrana-Torrelio, Carlos M.', 'Solovyov, Alexander', 'Ojeda-Flores, Rafael', 'Arrigo, Nicole C.', 'Islam, Ariful', 'Ali Khan, Shahneaz', 'Hosseini, Parviez', 'Bogich, Tiffany L.', 'Olival, Kevin J.', 'Sanchez-Leon, Maria D.', 'Karesh, William B.', 'Goldstein, Tracey', 'Luby, Stephen P.', 'Morse, Stephen S.', 'Mazet, Jonna A. K.', 'Daszak, Peter', 'Lipkin, W. Ian']",mBio,,,True
80d5f4abbc2555af4f370880ab4e0933d647ad99,PMC,A Strategy To Estimate Unknown Viral Diversity in Mammals,http://dx.doi.org/10.1128/mBio.00598-13,PMC3760253,24003179,CC BY-NC-SA,"The majority of emerging zoonoses originate in wildlife, and many are caused by viruses. However, there are no rigorous estimates of total viral diversity (here termed “virodiversity”) for any wildlife species, despite the utility of this to future surveillance and control of emerging zoonoses. In this case study, we repeatedly sampled a mammalian wildlife host known to harbor emerging zoonotic pathogens (the Indian Flying Fox, Pteropus giganteus) and used PCR with degenerate viral family-level primers to discover and analyze the occurrence patterns of 55 viruses from nine viral families. We then adapted statistical techniques used to estimate biodiversity in vertebrates and plants and estimated the total viral richness of these nine families in P. giganteus to be 58 viruses. Our analyses demonstrate proof-of-concept of a strategy for estimating viral richness and provide the first statistically supported estimate of the number of undiscovered viruses in a mammalian host. We used a simple extrapolation to estimate that there are a minimum of 320,000 mammalian viruses awaiting discovery within these nine families, assuming all species harbor a similar number of viruses, with minimal turnover between host species. We estimate the cost of discovering these viruses to be ~$6.3 billion (or ~$1.4 billion for 85% of the total diversity), which if annualized over a 10-year study time frame would represent a small fraction of the cost of many pandemic zoonoses.",2013 Sep 3,"['Anthony, Simon J.', 'Epstein, Jonathan H.', 'Murray, Kris A.', 'Navarrete-Macias, Isamara', 'Zambrana-Torrelio, Carlos M.', 'Solovyov, Alexander', 'Ojeda-Flores, Rafael', 'Arrigo, Nicole C.', 'Islam, Ariful', 'Ali Khan, Shahneaz', 'Hosseini, Parviez', 'Bogich, Tiffany L.', 'Olival, Kevin J.', 'Sanchez-Leon, Maria D.', 'Karesh, William B.', 'Goldstein, Tracey', 'Luby, Stephen P.', 'Morse, Stephen S.', 'Mazet, Jonna A. K.', 'Daszak, Peter', 'Lipkin, W. Ian']",mBio,,,False
38dca8e0460d2a290df1b0ff8e1cce1b611aa309,PMC,A Strategy To Estimate Unknown Viral Diversity in Mammals,http://dx.doi.org/10.1128/mBio.00598-13,PMC3760253,24003179,CC BY-NC-SA,"The majority of emerging zoonoses originate in wildlife, and many are caused by viruses. However, there are no rigorous estimates of total viral diversity (here termed “virodiversity”) for any wildlife species, despite the utility of this to future surveillance and control of emerging zoonoses. In this case study, we repeatedly sampled a mammalian wildlife host known to harbor emerging zoonotic pathogens (the Indian Flying Fox, Pteropus giganteus) and used PCR with degenerate viral family-level primers to discover and analyze the occurrence patterns of 55 viruses from nine viral families. We then adapted statistical techniques used to estimate biodiversity in vertebrates and plants and estimated the total viral richness of these nine families in P. giganteus to be 58 viruses. Our analyses demonstrate proof-of-concept of a strategy for estimating viral richness and provide the first statistically supported estimate of the number of undiscovered viruses in a mammalian host. We used a simple extrapolation to estimate that there are a minimum of 320,000 mammalian viruses awaiting discovery within these nine families, assuming all species harbor a similar number of viruses, with minimal turnover between host species. We estimate the cost of discovering these viruses to be ~$6.3 billion (or ~$1.4 billion for 85% of the total diversity), which if annualized over a 10-year study time frame would represent a small fraction of the cost of many pandemic zoonoses.",2013 Sep 3,"['Anthony, Simon J.', 'Epstein, Jonathan H.', 'Murray, Kris A.', 'Navarrete-Macias, Isamara', 'Zambrana-Torrelio, Carlos M.', 'Solovyov, Alexander', 'Ojeda-Flores, Rafael', 'Arrigo, Nicole C.', 'Islam, Ariful', 'Ali Khan, Shahneaz', 'Hosseini, Parviez', 'Bogich, Tiffany L.', 'Olival, Kevin J.', 'Sanchez-Leon, Maria D.', 'Karesh, William B.', 'Goldstein, Tracey', 'Luby, Stephen P.', 'Morse, Stephen S.', 'Mazet, Jonna A. K.', 'Daszak, Peter', 'Lipkin, W. Ian']",mBio,,,False
c2c158e065601e7d505c2635d3257cb6859c040f,PMC,A Strategy To Estimate Unknown Viral Diversity in Mammals,http://dx.doi.org/10.1128/mBio.00598-13,PMC3760253,24003179,CC BY-NC-SA,"The majority of emerging zoonoses originate in wildlife, and many are caused by viruses. However, there are no rigorous estimates of total viral diversity (here termed “virodiversity”) for any wildlife species, despite the utility of this to future surveillance and control of emerging zoonoses. In this case study, we repeatedly sampled a mammalian wildlife host known to harbor emerging zoonotic pathogens (the Indian Flying Fox, Pteropus giganteus) and used PCR with degenerate viral family-level primers to discover and analyze the occurrence patterns of 55 viruses from nine viral families. We then adapted statistical techniques used to estimate biodiversity in vertebrates and plants and estimated the total viral richness of these nine families in P. giganteus to be 58 viruses. Our analyses demonstrate proof-of-concept of a strategy for estimating viral richness and provide the first statistically supported estimate of the number of undiscovered viruses in a mammalian host. We used a simple extrapolation to estimate that there are a minimum of 320,000 mammalian viruses awaiting discovery within these nine families, assuming all species harbor a similar number of viruses, with minimal turnover between host species. We estimate the cost of discovering these viruses to be ~$6.3 billion (or ~$1.4 billion for 85% of the total diversity), which if annualized over a 10-year study time frame would represent a small fraction of the cost of many pandemic zoonoses.",2013 Sep 3,"['Anthony, Simon J.', 'Epstein, Jonathan H.', 'Murray, Kris A.', 'Navarrete-Macias, Isamara', 'Zambrana-Torrelio, Carlos M.', 'Solovyov, Alexander', 'Ojeda-Flores, Rafael', 'Arrigo, Nicole C.', 'Islam, Ariful', 'Ali Khan, Shahneaz', 'Hosseini, Parviez', 'Bogich, Tiffany L.', 'Olival, Kevin J.', 'Sanchez-Leon, Maria D.', 'Karesh, William B.', 'Goldstein, Tracey', 'Luby, Stephen P.', 'Morse, Stephen S.', 'Mazet, Jonna A. K.', 'Daszak, Peter', 'Lipkin, W. Ian']",mBio,,,False
e0c0c5277a24320d44e9b356e13c5801dad521af,PMC,Discovery of a divergent HPIV4 from respiratory secretions using second and third generation metagenomic sequencing,http://dx.doi.org/10.1038/srep02468,PMC3760282,24002378,CC BY-NC-ND,"Molecular detection of viruses has been aided by high-throughput sequencing, permitting the genomic characterization of emerging strains. In this study, we comprehensively screened 500 respiratory secretions from children with upper and/or lower respiratory tract infections for viral pathogens. The viruses detected are described, including a divergent human parainfluenza virus type 4 from GS FLX pyrosequencing of 92 specimens. Complete full-genome characterization of the virus followed, using Single Molecule, Real-Time (SMRT) sequencing. Subsequent “primer walking” combined with Sanger sequencing validated the RS platform's utility in viral sequencing from complex clinical samples. Comparative genomics reveals the divergent strain clusters with the only completely sequenced HPIV4a subtype. However, it also exhibits various structural features present in one of the HPIV4b reference strains, opening questions regarding their lifecycle and evolutionary relationships among these viruses. Clinical data from patients infected with the strain, as well as viral prevalence estimates using real-time PCR, is also described.",2013 Sep 3,"['Alquezar-Planas, David E.', 'Mourier, Tobias', 'Bruhn, Christian A. W.', 'Hansen, Anders J.', 'Vitcetz, Sarah Nathalie', 'Mørk, Søren', 'Gorodkin, Jan', 'Nielsen, Hanne Abel', 'Guo, Yan', 'Sethuraman, Anand', 'Paxinos, Ellen E.', 'Shan, Tongling', 'Delwart, Eric L.', 'Nielsen, Lars P.']",Sci Rep,,,True
19fb39e16fc35b4ca36825636d018beda55d3d42,PMC,Discovery of a divergent HPIV4 from respiratory secretions using second and third generation metagenomic sequencing,http://dx.doi.org/10.1038/srep02468,PMC3760282,24002378,CC BY-NC-ND,"Molecular detection of viruses has been aided by high-throughput sequencing, permitting the genomic characterization of emerging strains. In this study, we comprehensively screened 500 respiratory secretions from children with upper and/or lower respiratory tract infections for viral pathogens. The viruses detected are described, including a divergent human parainfluenza virus type 4 from GS FLX pyrosequencing of 92 specimens. Complete full-genome characterization of the virus followed, using Single Molecule, Real-Time (SMRT) sequencing. Subsequent “primer walking” combined with Sanger sequencing validated the RS platform's utility in viral sequencing from complex clinical samples. Comparative genomics reveals the divergent strain clusters with the only completely sequenced HPIV4a subtype. However, it also exhibits various structural features present in one of the HPIV4b reference strains, opening questions regarding their lifecycle and evolutionary relationships among these viruses. Clinical data from patients infected with the strain, as well as viral prevalence estimates using real-time PCR, is also described.",2013 Sep 3,"['Alquezar-Planas, David E.', 'Mourier, Tobias', 'Bruhn, Christian A. W.', 'Hansen, Anders J.', 'Vitcetz, Sarah Nathalie', 'Mørk, Søren', 'Gorodkin, Jan', 'Nielsen, Hanne Abel', 'Guo, Yan', 'Sethuraman, Anand', 'Paxinos, Ellen E.', 'Shan, Tongling', 'Delwart, Eric L.', 'Nielsen, Lars P.']",Sci Rep,,,True
c98acd548c24c973cbad72af49a0080fce9cd2ee,PMC,"Problem- and Case-Based Learning in Science: An Introduction to Distinctions, Values, and Outcomes",http://dx.doi.org/10.1187/cbe.12-11-0190,PMC3763004,24006385,CC BY-NC-SA,"Case-based learning and problem-based learning have demonstrated great promise in reforming science education. Yet an instructor, in newly considering this suite of interrelated pedagogical strategies, faces a number of important instructional choices. Different features and their related values and learning outcomes are profiled here, including: the level of student autonomy; instructional focus on content, skills development, or nature-of-science understanding; the role of history, or known outcomes; scope, clarity, and authenticity of problems provided to students; extent of collaboration; complexity, in terms of number of interpretive perspectives; and, perhaps most importantly, the role of applying versus generating knowledge.",2013 Fall,"Allchin, Douglas",CBE Life Sci Educ,,,True
fc3bce122003ef28564d0dfaec7bd5771cfa4bff,PMC,First detection of canine parvovirus type 2c in Brazil,http://dx.doi.org/10.1590/S1517-83822009000300008,PMC3768551,24031389,CC BY-NC,"The presence of canine parvovirus type 2 (CPV-2), 2a and 2b has been described in Brazil, however, the type 2c had not been reported until now. In the current study, seven out of nine samples from dogs with diarrhea were characterized as CPV-2c, indicating that this virus is already circulating in the Brazilian canine population.",2009 Sep 1 Jul-Sep,"['Streck, André Felipe', 'de Souza, Carine Kunzler', 'Gonçalves, Karla Rathje', 'Zang, Luciana', 'Pinto, Luciane Dubina', 'Canal, Cláudio Wageck']",Braz J Microbiol,,,True
23ffba1251c42cd4311635ab25afeba065146568,PMC,Differentiation of Bovine Coronavirus (Bcov) Genotypes by a Restriction Enzyme Assay,http://dx.doi.org/10.1590/S1517-83822010000300034,PMC3768659,24031559,CC BY-NC,"This article reports the use of the GsuI restriction enzyme to differentiate genotypes of Bovine Coronavirus (BCoV), based on an 18-nucleotide deletion of S1-coding region found in one of the two genotypes. It was concluded that this assay can be used as a rapid tool for BCoV genotypes differentiation.",2010 Sep 1 Jul-Sep,"['Pinheiro de Souza, Sibele', 'Miyuki Asano, Karen', 'Lucas Sandri, Thaisa', 'Nunes de Barros, Iracema', 'José Richtzenhain, Leonardo', 'Eduardo Brandão, Paulo']",Braz J Microbiol,,,True
107ff91ec95dea35a80145aebbe5322c08c57e5e,PMC,Rhinovirus detection using different PCR-based strategies,http://dx.doi.org/10.1590/S1517-83822012000200038,PMC3768804,24031885,CC BY-NC,"Human rhinoviruses (HRVs) are the major cause of the common cold. HRVs were recently reclassified into the Enterovirus genus (HEV) in the Picornaviridae family. HRVs and other members of the HEV genus share many common features, including sense RNA genomes and partial nucleotide sequence identity. The aim of this study was to evaluate different HRV detection strategies. Samples from adults with acute respiratory infection (n = 291) who were treated in Sao Paulo Hospital (2001-2003) were tested using three assays. The first assay detected picornaviruses by RT-PCR and hybridization, the second detected rhinoviruses using RT-PCR/sequencing, and the third differentiated HRV from HEV using duplex semi-nested-RT-PCR. Analysis of the results obtained from the first two strategies revealed 83% concordance. Discordant samples were then evaluated by the third protocol, and 82% were negative. The picornavirus detection protocol was more sensitive but less specific than the rhinovirus detection protocols. The semi-nested protocol utilized in the present study was less sensitive and was not useful in differentiating HRV from HEV. Sequencing assays examining different genes would address the best strategy of confirming rhinovirus and enterovirus infections.",2012 Jun 1 Apr-Jun,"['Silva, E.R.M.', 'Watanabe, A.S.A.', 'Carraro, E.', 'Perosa, A.H.S.', 'Granato, C.F.H.', 'Bellei, N.C.J.']",Braz J Microbiol,,,True
5b2c74eaf9dc747307ec2d91ba16771cd505e44c,PMC,Isolation and identification of feline calicivirus and feline herpesvirus in Southern Brazil,http://dx.doi.org/10.1590/S1517-83822012000200017,PMC3768834,24031864,CC BY-NC,"Feline calicivirus (FCV) and feline herpesvirus type 1 (FHV-1) are the two primary causes of upper respiratory tract disease in cats. The aim of this study was to demonstrate the distribution of FCV and FHV-1 among the feline population of several counties in Rio Grande do Sul State, Brazil. To this end, conjunctival and nasal swabs were collected from 302 cats from different locations, including households, breeding catteries, veterinary clinics, animal hospitals and experimental research facilities. The samples were collected between July 2006 to June 2009. The virus isolation was performed in CRFK cells and, subsequently, the identification was confirmed by PCR. FCV, FHV-1, or both were isolated from 55 cats from 28 different locations. FCV alone was isolated from 52.7% (29/55) of the animals that tested positively, FHV-1 alone was isolated from 38.2% (21/55) of the animals that tested positively, and co-infection were detected in 9.1% (5/55) of the animals that tested positively. Virus detection was more prevalent in cats that were less than 1 year old, among animals that shared a living space with other cats, and females. FCV and FHV-1 were isolated from vaccinated cats. In addition, both viruses were isolated from cats that showed no signs of disease. The results suggest that a carrier state is common for both viruses in the evaluated population. A search for other causes of respiratory disease in that population is necessary; and further studies relating to the molecular characterization of viruses and vaccine efficacy are also necessary.",2012 Jun 1 Apr-Jun,"['Henzel, Andréia', 'Brum, Mário Celso Sperotto', 'Lautert, Cláudia', 'Martins, Mathias', 'Lovato, Luciane Teresinha', 'Weiblen, Rudi']",Braz J Microbiol,,,True
31390ea0f2fc73d3cd3fee80ca0de765ddd68429,PMC,Seasonality of viral respiratory infections in southeast of Brazil: the influence of temperature and air humidity,http://dx.doi.org/10.1590/S1517-838220120001000011,PMC3768995,24031808,CC BY-NC,"Viruses are the major cause of lower respiratory tract infections in childhood and the main viruses involved are Human Respiratory Syncytial Virus (HRSV), Human Metapneumovirus (HMPV), Influenzavirus A and B (FLUA and FLUB), Human Parainfluenza Virus 1, 2 and 3 (HPIV1, 2 and 3) and Human Rhinovirus (HRV). The purposes of this study were to detect respiratory viruses in hospitalized children younger than six years and identify the influence of temperature and relative air humidity on the detected viruses. Samples of nasopharyngeal washes were collected from hospitalized children between May/2004 and September/2005. Methods of viral detection were RT-PCR, PCR and HRV amplicons were confirmed by hybridization. Results showed 54% (148/272) of viral positivity. HRSV was detected in 29% (79/272) of the samples; HRV in 23.1% (63/272); HPIV3 in 5.1% (14/272); HMPV in 3.3% (9/272); HPIV1 in 2.9% (8/272); FLUB in 1.4% (4/272), FLUA in 1.1% (3/272), and HPIV2 in 0.3% (1/272). The highest detection rates occurred mainly in the spring 2004 and in the autumn 2005. It was observed that viral respiratory infections tend to increase as the relative air humidity decreases, showing significant association with monthly averages of minimal temperature and minimal relative air humidity. In conclusion, viral respiratory infections vary according to temperature and relative air humidity and viral respiratory infections present major incidences it coldest and driest periods.",2012 Jun 1 Jan-Mar,"['Gardinassi, Luiz Gustavo', 'Marques Simas, Paulo Vitor', 'Salomão, João Batista', 'Durigon, Edison Luiz', 'Zanetta Trevisan, Dirce Maria', 'Cordeiro, José Antonio', 'Lacerda, Mauricio Nogueira', 'Rahal, Paula', 'de Souz, Fátima Pereira']",Braz J Microbiol,,,True
3dd8351aa51cbbf5dbfbd90a569efbad88b57b36,PMC,Human rhinovirus infections in symptomatic and asymptomatic subjects,http://dx.doi.org/10.1590/S1517-838220120004000049,PMC3769032,24031996,CC BY-NC,"The role of rhinovirus asymptomatic infections in the transmission among close contacts subjects is unknown. We tested health care workers, a pair of one child and a family member and immunocompromised patients (n =191). HRV were detected on 22.9% symptomatic and 3.6% asymptomatic cases suggesting lower transmission among contacts.",2012 Jun 1 Oct-Dec,"['Camargo, C.N.', 'Carraro, E.', 'Granato, C.F.', 'Bellei, N.']",Braz J Microbiol,,,True
377786fe05588ea782213fcb92f39a6522f113bd,PMC,Epidemiological aspects of astrovirus and coronavirus in poults in the South Eastern Region of Brazil,http://dx.doi.org/10.1590/S1517-83822009000200008,PMC3769739,24031353,CC BY-NC,"A survey of Turkey Coronavirus (TCoV) and Astrovirus (TAstV-2) prevalence was carried out from February to December during 2006 year in semiarid region of Brazil, from a turkey producer area, localized in South Eastern of Brazil. To asses the risk factor related to clinical material, climatic condition and type of RT-PCR applied, cloacal swabs (CS), faeces, sera, bursa of Fabricius (BF), thymus (TH) and spleen (SP) and ileum-caeca region were collected from 30-day-old poults suffering of enteritis episode characterized as poult enteritis mortality syndrome (PEMS). The PEMS clinical features were characterized by watery to foamy faeces, light brown-yellow in colour and low mortality rate. Meteorological data (rainfall and relative humidity) observed during along the study presented monthly average temperature ranging from 39.3 and 31.2ºC, precipitation in rainy season from 40 to 270.3 mm/month, and no rain during dry season. Simplex RT-PCR gave odds ratio (OR) values suggesting that ileum-caeca region is at higher chance (OR=1.9; p=0.9741) to have both viral RNA than faeces (OR=1.5; p=0.7319). However, multiplex RT-PCR showed 3.98 (p=0.89982) more chance to give positive results in faeces than CS at dry season. The major risk factors seem to be low rate of humidity and high temperatures at winter, probably responsible for spread, easily, the TCoV and TAstv-2 among the flocks. The positive results of both virus suggested that they can play an important role in enteric disorders, associated to low humidity and high temperatures frequently found in tropical countries.",2009 Jun 1 Apr-Jun,"['da Silva, S.E.L.', 'Bonetti, A.M.', 'Petrocelli, A.', 'Ferrari, H.F.', 'Luvizotto, M.C.R.', 'Cardoso, T.C.']",Braz J Microbiol,,,True
2b5a2503522ac52b24f3475d69719626993d9dab,PMC,Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine,http://dx.doi.org/10.2147/DDDT.S44401,PMC3771849,24039404,CC BY-NC,"Microneedles were first conceptualized for drug delivery many decades ago, overcoming the shortages and preserving the advantages of hypodermic needle and conventional transdermal drug-delivery systems to some extent. Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. This review describes microneedle geometry and the representative dissolving and biodegradable microneedle delivery methods via the skin, followed by the fabricating methods. Finally, this review puts forward some perspectives that require further investigation.",2013 Sep 4,"['Hong, Xiaoyun', 'Wei, Liangming', 'Wu, Fei', 'Wu, Zaozhan', 'Chen, Lizhu', 'Liu, Zhenguo', 'Yuan, Weien']",Drug Des Devel Ther,,,True
71b1e5b3dcbccd130699fbbdbc537a66a24598bc,PMC,"Engineering a Replication-Competent, Propagation-Defective Middle East Respiratory Syndrome Coronavirus as a Vaccine Candidate",http://dx.doi.org/10.1128/mBio.00650-13,PMC3774192,24023385,CC BY-NC-SA,"Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging coronavirus infecting humans that is associated with acute pneumonia, occasional renal failure, and a high mortality rate and is considered a threat to public health. The construction of a full-length infectious cDNA clone of the MERS-CoV genome in a bacterial artificial chromosome is reported here, providing a reverse genetics system to study the molecular biology of the virus and to develop attenuated viruses as vaccine candidates. Following transfection with the cDNA clone, infectious virus was rescued in both Vero A66 and Huh-7 cells. Recombinant MERS-CoVs (rMERS-CoVs) lacking the accessory genes 3, 4a, 4b, and 5 were successfully rescued from cDNA clones with these genes deleted. The mutant viruses presented growth kinetics similar to those of the wild-type virus, indicating that accessory genes were not essential for MERS-CoV replication in cell cultures. In contrast, an engineered mutant virus lacking the structural E protein (rMERS-CoV-ΔE) was not successfully rescued, since viral infectivity was lost at early passages. Interestingly, the rMERS-CoV-ΔE genome replicated after cDNA clone was transfected into cells. The infectious virus was rescued and propagated in cells expressing the E protein in trans, indicating that this virus was replication competent and propagation defective. Therefore, the rMERS-CoV-ΔE mutant virus is potentially a safe and promising vaccine candidate to prevent MERS-CoV infection. IMPORTANCE  Since the emergence of MERS-CoV in the Arabian Peninsula during the summer of 2012, it has already spread to 10 different countries, infecting around 94 persons and showing a mortality rate higher than 50%. This article describes the development of the first reverse genetics system for MERS-CoV, based on the construction of an infectious cDNA clone inserted into a bacterial artificial chromosome. Using this system, a collection of rMERS-CoV deletion mutants has been generated. Interestingly, one of the mutants with the E gene deleted was a replication-competent, propagation-defective virus that could only be grown in the laboratory by providing E protein in trans, whereas it would only survive a single virus infection cycle in vivo. This virus constitutes a vaccine candidate that may represent a balance between safety and efficacy for the induction of mucosal immunity, which is needed to prevent MERS-CoV infection.",2013 Sep 10,"['Almazán, Fernando', 'DeDiego, Marta L.', 'Sola, Isabel', 'Zuñiga, Sonia', 'Nieto-Torres, Jose L.', 'Marquez-Jurado, Silvia', 'Andrés, German', 'Enjuanes, Luis']",mBio,,,True
035dc4021101af0a19152cb5ea7b40b0c57ed76d,PMC,The Battle Between Influenza and the Innate Immune Response in the Human Respiratory Tract,http://dx.doi.org/10.3947/ic.2013.45.1.11,PMC3780943,24265946,CC BY-NC,"Influenza is a viral infection of the respiratory tract. Infection is normally confined to the upper respiratory tract but certain viral strains have evolved the ability to infect the lower respiratory tract, including the alveoli, leading to inflammation and a disease pattern of diffuse alveolar damage. Factors leading to this sequence of events are novel influenza strains, or strains that have viral proteins, in particular the NS1 protein that allow it to escape the innate immune system. There are three main barriers that prevent infection of pneumocytes - mucin, host defence lectins and cells such as macrophages. Viruses have developed strategies such as neuraminidase and glycosylation patterns that allow this evasion. Though there has been much investment in antiviral drugs, it is proposed that more attention should be directed towards developing or utilizing compounds that enhance the ability of the innate immune system to combat viral infection.",2013 Mar 29,"Nicholls, John M",Infect Chemother,,,True
6214d0592f9322221375a64360716a1cae0add5f,PMC,Barrier function of airway tract epithelium,http://dx.doi.org/10.4161/tisb.24997,PMC3783221,24665407,CC BY-NC,"Airway epithelium contributes significantly to the barrier function of airway tract. Mucociliary escalator, intercellular apical junctional complexes which regulate paracellular permeability and antimicrobial peptides secreted by the airway epithelial cells are the three primary components of barrier function of airway tract. These three components act cooperatively to clear inhaled pathogens, allergens and particulate matter without inducing inflammation and maintain tissue homeostasis. Therefore impairment of one or more of these essential components of barrier function may increase susceptibility to infection and promote exaggerated and prolonged innate immune responses to environmental factors including allergens and pathogens resulting in chronic inflammation. Here we review the regulation of components of barrier function with respect to chronic airways diseases.",2013 Oct 1,"['Ganesan, Shyamala', 'Comstock, Adam T', 'Sajjan, Uma S']",Tissue Barriers,,,True
77fcb3d2473e9f9c05c8f0bce3f4ebecdd5252ca,PMC,"The Advantages and Limitations of International Classification of Diseases, Injuries and Causes of Death from Aspect of Existing Health Care System of Bosnia and Herzegovina",http://dx.doi.org/10.5455/aim.2008.16.159-161,PMC3789162,24109155,CC BY-NC,CONFLICT OF INTEREST: NONE DECLARED INTRODUCTION: The International classification of diseases (ICD) is the most important classification in medicine. It is used by all medical professionals. CONCEPT: The basic concept of ICD is founded on the standardization of the nomenclature for the names of diseases and their basic systematization in the hierarchically structured category. ADVANTAGES AND DISADVANTAGES: The health care provider institutions such as hospitals are subjects that should facilitate implementation of medical applications that follows the patient medical condition and facts connected with him. The definitive diagnosis that can be coded using ICD can be achieved after several visits of patient and rarely during the first visit. CONCLUSION: The ICD classification is one of the oldest and most important classifications in medicine. In the scope of ICD are all fields of medicine. It is used in statistical purpose and as a coding system in medical databases.,2008 Sep,"['Kurbasic, Izeta', 'Pandza, Haris', 'Masic, Izet', 'Huseinagic, Senad', 'Tandir, Salih', 'Alicajic, Fredi', 'Toromanovic, Selim']",Acta Inform Med,,,True
6803ffb755ca44defc371b10e0ad52ccdbb67108,PMC,Major advances in managing community-acquired pneumonia,http://dx.doi.org/10.12703/P5-43,PMC3790563,24167724,CC BY-NC,"This article is a non-systematic review of selected recent publications in community-acquired pneumonia, including a comparison of various guidelines. Risk stratification of patients has recently been advanced by the addition of several useful biomarkers. The issue of single versus dual antibiotic treatment remains controversial and awaits a conclusive randomized controlled trial. However, in the meantime, there is a working consensus that more severe patients should receive dual therapy.",2013 Oct 1,"['Asrar Khan, Waseem', 'Woodhead, Mark']",F1000Prime Rep,,,True
cf899b3942af5e7e734cca1ce4f6ff1a1c82a9d9,PMC,Characteristics of human infection with avian influenza viruses and development of new antiviral agents,http://dx.doi.org/10.1038/aps.2013.121,PMC3791557,24096642,CC BY-NC-ND,"Since 1997, several epizootic avian influenza viruses (AIVs) have been transmitted to humans, causing diseases and even deaths. The recent emergence of severe human infections with AIV (H7N9) in China has raised concerns about efficient interpersonal viral transmission, polygenic traits in viral pathogenicity and the management of newly emerging strains. The symptoms associated with viral infection are different in various AI strains: H5N1 and newly emerged H7N9 induce severe pneumonia and related complications in patients, while some H7 and H9 subtypes cause only conjunctivitis or mild respiratory symptoms. The virulence and tissue tropism of viruses as well as the host responses contribute to the pathogenesis of human AIV infection. Several preventive and therapeutic approaches have been proposed to combat AIV infection, including antiviral drugs such as M2 inhibitors, neuraminidase inhibitors, RNA polymerase inhibitors, attachment inhibitors and signal-transduction inhibitors etc. In this article, we summarize the recent progress in researches on the epidemiology, clinical features, pathogenicity determinants, and available or potential antivirals of AIV.",2013 Oct 7,"['Liu, Qiang', 'Liu, Dong-ying', 'Yang, Zhan-qiu']",Acta Pharmacol Sin,,,True
0e507b6bf5817d101821946e8091c60df6b26c97,PMC,"Probable person to person transmission of novel avian influenza A (H7N9) virus in Eastern China, 2013: epidemiological investigation",http://dx.doi.org/10.1136/bmj.f4752,PMC3805478,23920350,CC BY-NC,"Objective To determine whether the novel avian influenza H7N9 virus can transmit from person to person and its efficiency. Design Epidemiological investigations conducted after a family cluster of two patients with avian H7N9 in March 2013. Setting Wuxi, Eastern China. Participants Two patients, their close contacts, and relevant environments. Samples from the patients and environments were collected and tested by real time reverse transcriptase-polymerase chain reaction (rRT-PCR), viral culture, and haemagglutination inhibition assay. Any contacts who became ill had samples tested for avian H7N9 by rRT-PCR. Paired serum samples were obtained from contacts for serological testing by haemagglutination inhibition assays. Main outcomes measures Clinical data, history of exposure before the onset of illnesses, and results of laboratory testing of pathogens and further analysis of sequences and phylogenetic tree to isolated strains. Results The index patient became ill five to six days after his last exposure to poultry. The second patient, his daughter aged 32, who provided unprotected bedside care in the hospital, had no known exposure to poultry. She developed symptoms six days after her last contact with her father. Two strains were isolated successfully from the two patients. Genome sequence and analyses of phylogenetic trees showed that both viruses were almost genetically identical. Forty three close contacts of both patients were identified. One had mild illness but had negative results for avian H7N9 by rRT-PCR. All 43 close contacts tested negative for haemagglutination inhibition antibodies specific for avian H7N9. Conclusions The infection of the daughter probably resulted from contact with her father (the index patient) during unprotected exposure, suggesting that in this cluster the virus was able to transmit from person to person. The transmissibility was limited and non-sustainable.",2013 Aug 6,"['Qi, Xian', 'Qian, Yan-Hua', 'Bao, Chang-Jun', 'Guo, Xi-Ling', 'Cui, Lun-Biao', 'Tang, Fen-Yang', 'Ji, Hong', 'Huang, Yong', 'Cai, Pei-Quan', 'Lu, Bing', 'Xu, Ke', 'Shi, Chao', 'Zhu, Feng-Cai', 'Zhou, Ming-Hao', 'Wang, Hua']",BMJ,,,False
b41c248face9f4bfc9245367660f7ce3a5772fac,PMC,"Probable person to person transmission of novel avian influenza A (H7N9) virus in Eastern China, 2013: epidemiological investigation",http://dx.doi.org/10.1136/bmj.f4752,PMC3805478,23920350,CC BY-NC,"Objective To determine whether the novel avian influenza H7N9 virus can transmit from person to person and its efficiency. Design Epidemiological investigations conducted after a family cluster of two patients with avian H7N9 in March 2013. Setting Wuxi, Eastern China. Participants Two patients, their close contacts, and relevant environments. Samples from the patients and environments were collected and tested by real time reverse transcriptase-polymerase chain reaction (rRT-PCR), viral culture, and haemagglutination inhibition assay. Any contacts who became ill had samples tested for avian H7N9 by rRT-PCR. Paired serum samples were obtained from contacts for serological testing by haemagglutination inhibition assays. Main outcomes measures Clinical data, history of exposure before the onset of illnesses, and results of laboratory testing of pathogens and further analysis of sequences and phylogenetic tree to isolated strains. Results The index patient became ill five to six days after his last exposure to poultry. The second patient, his daughter aged 32, who provided unprotected bedside care in the hospital, had no known exposure to poultry. She developed symptoms six days after her last contact with her father. Two strains were isolated successfully from the two patients. Genome sequence and analyses of phylogenetic trees showed that both viruses were almost genetically identical. Forty three close contacts of both patients were identified. One had mild illness but had negative results for avian H7N9 by rRT-PCR. All 43 close contacts tested negative for haemagglutination inhibition antibodies specific for avian H7N9. Conclusions The infection of the daughter probably resulted from contact with her father (the index patient) during unprotected exposure, suggesting that in this cluster the virus was able to transmit from person to person. The transmissibility was limited and non-sustainable.",2013 Aug 6,"['Qi, Xian', 'Qian, Yan-Hua', 'Bao, Chang-Jun', 'Guo, Xi-Ling', 'Cui, Lun-Biao', 'Tang, Fen-Yang', 'Ji, Hong', 'Huang, Yong', 'Cai, Pei-Quan', 'Lu, Bing', 'Xu, Ke', 'Shi, Chao', 'Zhu, Feng-Cai', 'Zhou, Ming-Hao', 'Wang, Hua']",BMJ,,,False
65d508add328dceec3427a9bc54cff552b6a2271,PMC,Development of a risk assessment tool for contact tracing people after contact with infectious patients while travelling by bus or other public ground transport: a Delphi consensus approach,http://dx.doi.org/10.1136/bmjopen-2013-002939,PMC3808761,24157815,CC BY-NC,"BACKGROUND: Tracing persons who have been in contact with an infectious patient may be very effective in preventing the spread of communicable diseases. However, criteria to decide when to conduct contact tracing are not well established. We have investigated the available evidence for contact tracing with a focus on public ground transport aiming to give guidance in what situations contact tracing should be considered. METHODS: Relevant infectious diseases suitable for contact tracing in ground transport and a set of disease-specific epidemiological criteria were defined through literature search and structured multistep expert consultations. We developed continuous scales for each criterion to be rated for its relevance to contact tracing in ground transport. We used the Delphi method with an international expert panel to position the values of criteria on the respective scales. RESULTS: The study led to the development of the ‘Contact Tracing-Risk Assessment Profile’ (CT-RAP), a decision-making instrument, taking into account pathogen-specific as well as situation-specific criteria. This report describes the methodology of this instrument and presents two examples of ready-to-use CT-RAP for tuberculosis and for meningococcal disease in public ground transport. DISCUSSION: The systematic and transparent use of the CT-RAP for tuberculosis and meningococcal disease is likely to facilitate reasonable, efficient and user-friendly decisions with respect to contact tracing. New CT-RAPs for additional pathogens and different settings such as schools and kindergartens are being planned.",2013 Oct 24,"['Mohr, Oliver', 'Hermes, Julia', 'Schink, Susanne B', 'Askar, Mona', 'Menucci, Daniel', 'Swaan, Corien', 'Goetsch, Udo', 'Monk, Philip', 'Eckmanns, Tim', 'Poggensee, Gabriele', 'Krause, Gérard']",BMJ Open,,,True
319017db7033f2754fd403feb01c1fa2b26f38cc,PMC,Development of a risk assessment tool for contact tracing people after contact with infectious patients while travelling by bus or other public ground transport: a Delphi consensus approach,http://dx.doi.org/10.1136/bmjopen-2013-002939,PMC3808761,24157815,CC BY-NC,"BACKGROUND: Tracing persons who have been in contact with an infectious patient may be very effective in preventing the spread of communicable diseases. However, criteria to decide when to conduct contact tracing are not well established. We have investigated the available evidence for contact tracing with a focus on public ground transport aiming to give guidance in what situations contact tracing should be considered. METHODS: Relevant infectious diseases suitable for contact tracing in ground transport and a set of disease-specific epidemiological criteria were defined through literature search and structured multistep expert consultations. We developed continuous scales for each criterion to be rated for its relevance to contact tracing in ground transport. We used the Delphi method with an international expert panel to position the values of criteria on the respective scales. RESULTS: The study led to the development of the ‘Contact Tracing-Risk Assessment Profile’ (CT-RAP), a decision-making instrument, taking into account pathogen-specific as well as situation-specific criteria. This report describes the methodology of this instrument and presents two examples of ready-to-use CT-RAP for tuberculosis and for meningococcal disease in public ground transport. DISCUSSION: The systematic and transparent use of the CT-RAP for tuberculosis and meningococcal disease is likely to facilitate reasonable, efficient and user-friendly decisions with respect to contact tracing. New CT-RAPs for additional pathogens and different settings such as schools and kindergartens are being planned.",2013 Oct 24,"['Mohr, Oliver', 'Hermes, Julia', 'Schink, Susanne B', 'Askar, Mona', 'Menucci, Daniel', 'Swaan, Corien', 'Goetsch, Udo', 'Monk, Philip', 'Eckmanns, Tim', 'Poggensee, Gabriele', 'Krause, Gérard']",BMJ Open,,,True
55c6c45ee6b507c669c9a4832780b30a30838578,PMC,Development of a risk assessment tool for contact tracing people after contact with infectious patients while travelling by bus or other public ground transport: a Delphi consensus approach,http://dx.doi.org/10.1136/bmjopen-2013-002939,PMC3808761,24157815,CC BY-NC,"BACKGROUND: Tracing persons who have been in contact with an infectious patient may be very effective in preventing the spread of communicable diseases. However, criteria to decide when to conduct contact tracing are not well established. We have investigated the available evidence for contact tracing with a focus on public ground transport aiming to give guidance in what situations contact tracing should be considered. METHODS: Relevant infectious diseases suitable for contact tracing in ground transport and a set of disease-specific epidemiological criteria were defined through literature search and structured multistep expert consultations. We developed continuous scales for each criterion to be rated for its relevance to contact tracing in ground transport. We used the Delphi method with an international expert panel to position the values of criteria on the respective scales. RESULTS: The study led to the development of the ‘Contact Tracing-Risk Assessment Profile’ (CT-RAP), a decision-making instrument, taking into account pathogen-specific as well as situation-specific criteria. This report describes the methodology of this instrument and presents two examples of ready-to-use CT-RAP for tuberculosis and for meningococcal disease in public ground transport. DISCUSSION: The systematic and transparent use of the CT-RAP for tuberculosis and meningococcal disease is likely to facilitate reasonable, efficient and user-friendly decisions with respect to contact tracing. New CT-RAPs for additional pathogens and different settings such as schools and kindergartens are being planned.",2013 Oct 24,"['Mohr, Oliver', 'Hermes, Julia', 'Schink, Susanne B', 'Askar, Mona', 'Menucci, Daniel', 'Swaan, Corien', 'Goetsch, Udo', 'Monk, Philip', 'Eckmanns, Tim', 'Poggensee, Gabriele', 'Krause, Gérard']",BMJ Open,,,False
977370a5432431d0680323ce3f9e67db65f5f7b1,PMC,"Origin, Evolution, and Genotyping of Emergent Porcine Epidemic Diarrhea Virus Strains in the United States",http://dx.doi.org/10.1128/mBio.00737-13,PMC3812708,24129257,CC BY-NC-SA,"Coronaviruses are known to infect humans and other animals and cause respiratory and gastrointestinal diseases. Here we report the emergence of porcine epidemic diarrhea virus (PEDV) in the United States and determination of its origin, evolution, and genotypes based on temporal and geographical evidence. Histological lesions in small intestine sections of affected pigs and the complete genomic sequences of three emergent strains of PEDV isolated from outbreaks in Minnesota and Iowa were characterized. Genetic and phylogenetic analyses of the three U.S. strains revealed a close relationship with Chinese PEDV strains and their likely Chinese origin. The U.S. PEDV strains underwent evolutionary divergence, which can be classified into two sublineages. The three emergent U.S. strains are most closely related to a strain isolated in 2012 from Anhui Province in China, which might be the result of multiple recombination events between different genetic lineages or sublineages of PEDV. Molecular clock analysis of the divergent time based on the complete genomic sequences is consistent with the actual time difference, approximately 2 to 3 years, of the PED outbreaks between China (December 2010) and the United States (May 2013). The finding that the emergent U.S. PEDV strains share unique genetic features at the 5′-untranslated region with a bat coronavirus provided further support of the evolutionary origin of PEDV from bats and potential cross-species transmission. The data from this study have important implications for understanding the ongoing PEDV outbreaks in the United States and will guide future efforts to develop effective preventive and control measures against PEDV.",2013 Oct 15,"['Huang, Yao-Wei', 'Dickerman, Allan W.', 'Piñeyro, Pablo', 'Li, Long', 'Fang, Li', 'Kiehne, Ross', 'Opriessnig, Tanja', 'Meng, Xiang-Jin']",mBio,,,True
a2430aa85e30ab2583cd72c6321f5dfe7aa72bf1,PMC,"Origin, Evolution, and Genotyping of Emergent Porcine Epidemic Diarrhea Virus Strains in the United States",http://dx.doi.org/10.1128/mBio.00737-13,PMC3812708,24129257,CC BY-NC-SA,"Coronaviruses are known to infect humans and other animals and cause respiratory and gastrointestinal diseases. Here we report the emergence of porcine epidemic diarrhea virus (PEDV) in the United States and determination of its origin, evolution, and genotypes based on temporal and geographical evidence. Histological lesions in small intestine sections of affected pigs and the complete genomic sequences of three emergent strains of PEDV isolated from outbreaks in Minnesota and Iowa were characterized. Genetic and phylogenetic analyses of the three U.S. strains revealed a close relationship with Chinese PEDV strains and their likely Chinese origin. The U.S. PEDV strains underwent evolutionary divergence, which can be classified into two sublineages. The three emergent U.S. strains are most closely related to a strain isolated in 2012 from Anhui Province in China, which might be the result of multiple recombination events between different genetic lineages or sublineages of PEDV. Molecular clock analysis of the divergent time based on the complete genomic sequences is consistent with the actual time difference, approximately 2 to 3 years, of the PED outbreaks between China (December 2010) and the United States (May 2013). The finding that the emergent U.S. PEDV strains share unique genetic features at the 5′-untranslated region with a bat coronavirus provided further support of the evolutionary origin of PEDV from bats and potential cross-species transmission. The data from this study have important implications for understanding the ongoing PEDV outbreaks in the United States and will guide future efforts to develop effective preventive and control measures against PEDV.",2013 Oct 15,"['Huang, Yao-Wei', 'Dickerman, Allan W.', 'Piñeyro, Pablo', 'Li, Long', 'Fang, Li', 'Kiehne, Ross', 'Opriessnig, Tanja', 'Meng, Xiang-Jin']",mBio,,,False
2465921eecfd74ad6949ea6a90cfec144e3809ce,PMC,"Origin, Evolution, and Genotyping of Emergent Porcine Epidemic Diarrhea Virus Strains in the United States",http://dx.doi.org/10.1128/mBio.00737-13,PMC3812708,24129257,CC BY-NC-SA,"Coronaviruses are known to infect humans and other animals and cause respiratory and gastrointestinal diseases. Here we report the emergence of porcine epidemic diarrhea virus (PEDV) in the United States and determination of its origin, evolution, and genotypes based on temporal and geographical evidence. Histological lesions in small intestine sections of affected pigs and the complete genomic sequences of three emergent strains of PEDV isolated from outbreaks in Minnesota and Iowa were characterized. Genetic and phylogenetic analyses of the three U.S. strains revealed a close relationship with Chinese PEDV strains and their likely Chinese origin. The U.S. PEDV strains underwent evolutionary divergence, which can be classified into two sublineages. The three emergent U.S. strains are most closely related to a strain isolated in 2012 from Anhui Province in China, which might be the result of multiple recombination events between different genetic lineages or sublineages of PEDV. Molecular clock analysis of the divergent time based on the complete genomic sequences is consistent with the actual time difference, approximately 2 to 3 years, of the PED outbreaks between China (December 2010) and the United States (May 2013). The finding that the emergent U.S. PEDV strains share unique genetic features at the 5′-untranslated region with a bat coronavirus provided further support of the evolutionary origin of PEDV from bats and potential cross-species transmission. The data from this study have important implications for understanding the ongoing PEDV outbreaks in the United States and will guide future efforts to develop effective preventive and control measures against PEDV.",2013 Oct 15,"['Huang, Yao-Wei', 'Dickerman, Allan W.', 'Piñeyro, Pablo', 'Li, Long', 'Fang, Li', 'Kiehne, Ross', 'Opriessnig, Tanja', 'Meng, Xiang-Jin']",mBio,,,False
a41e8928ee5cb212550be0620946d6e62c34b001,PMC,The potential of the human immune system to develop broadly neutralizing HIV-1 antibodies: implications for vaccine development,http://dx.doi.org/10.1097/QAD.0000000000000015,PMC3815086,24100711,CC BY-NC-ND,"OBJECTIVES AND DESIGN: Developing an effective HIV-1 vaccine that elicits broadly neutralizing HIV-1 human antibodies (bnAbs) remains a challenging goal. Extensive studies on HIV-1 have revealed various strategies employed by the virus to escape host immune surveillance. Here, we investigated the human antibody gene repertoires of uninfected and HIV-1-infected individuals at genomic DNA (gDNA) and cDNA levels by deep sequencing followed by high-throughput sequence analysis to determine the frequencies of putative germline antibody genes of known HIV-1 monoclonal bnAbs (bnmAbs). METHODS: Combinatorial gDNA and cDNA antibody libraries were constructed using the gDNAs and mRNAs isolated from uninfected and HIV-1-infected human peripheral blood mononuclear cells (PBMCs). All libraries were deep sequenced and sequences analysed using IMGT/HighV-QUEST software (http://imgt.org/HighV-QUEST/index.action). The frequencies of putative germline antibodies of known bnmAbs in the gDNA and cDNA libraries were determined. RESULTS AND CONCLUSION: The human gDNA antibody libraries were more diverse in heavy and light chain V-gene lineage usage than the cDNA libraries, indicating that the human gDNA antibody gene repertoires may have more potential than the cDNA repertoires to develop HIV-1 bnAbs. The frequencies of the heavy and kappa and lambda light chain variable regions with identical V(D)J recombinations to known HIV-1 bnmAbs were extremely low in human antibody gene repertoires. However, we found relatively high frequencies of the heavy and kappa and lambda light chain variable regions that used the same V-genes and had the same CDR3 lengths as known HIV-1 bnmAbs regardless of (D)J-gene usage. B-cells bearing B-cell receptors of such heavy and kappa and lambda light chain variable regions may be stimulated to induce HIV-1 bnAbs.",2013 Oct 23,"['Zhang, Yu', 'Yuan, Tingting', 'Li, Jingjing', 'Zhang, Yanyu', 'Xu, Jianqing', 'Shao, Yiming', 'Chen, Zhiwei', 'Zhang, Mei-Yun']",AIDS,,,True
6e6e7f0218c6b5affa20bb27bb263517a113f7b1,PMC,Respiratory Syncytial Virus (RSV) Modulation at the Virus-Host Interface Affects Immune Outcome and Disease Pathogenesis,http://dx.doi.org/10.4110/in.2013.13.5.163,PMC3817296,24198740,CC BY-NC,"The dynamics of the virus-host interface in the response to respiratory virus infection is not well-understood; however, it is at this juncture that host immunity to infection evolves. Respiratory viruses have been shown to modulate the host response to gain a replication advantage through a variety of mechanisms. Viruses are parasites and must co-opt host genes for replication, and must interface with host cellular machinery to achieve an optimal balance between viral and cellular gene expression. Host cells have numerous strategies to resist infection, replication and virus spread, and only recently are we beginning to understand the network and pathways affected. The following is a short review article covering some of the studies associated with the Tripp laboratory that have addressed how respiratory syncytial virus (RSV) operates at the virus-host interface to affects immune outcome and disease pathogenesis.",2013 Oct 26,"Tripp, Ralph A.",Immune Netw,,,True
5ea02beeb65f975de027e3b6fedc6b239e9f2e8f,PMC,A Universal Protein Tag for Delivery of SiRNA-Aptamer Chimeras,http://dx.doi.org/10.1038/srep03129,PMC3819613,24196104,CC BY-NC-SA,"siRNA-aptamer chimeras have emerged as one of the most promising approaches for targeted delivery of siRNA due to the modularity of their diblock RNA structure, relatively lower cost over other targeted delivery approaches, and, most importantly, the outstanding potential for clinical translation. However, additional challenges must be addressed for efficient RNA interference (RNAi), in particular, endosomal escape. Currently, vast majority of siRNA delivery vehicles are based on cationic materials, which form complexes with negatively charged siRNA. Unfortunately, these approaches complicate the formulations again by forming large complexes with heterogeneous sizes, unfavorable surface charges, colloidal instability, and poor targeting ligand orientation. Here, we report the development of a small and simple protein tag that complements the therapeutic and targeting functionalities of chimera with two functional domains: a dsRNA binding domain (dsRBD) for siRNA docking and a pH-dependent polyhistidine to disrupt endosomal membrane. The protein selectively tags along the siRNA block of individual chimera, rendering the overall size of the complex small, desirable for deep tissue penetration, and the aptamer block accessible for target recognition. More interestingly, we found that extending the c-terminal polyhistidine segment in the protein tag to 18 amino acids completely abolishes the RNA binding function of dsRBD.",2013 Nov 7,"['Liu, Hong Yan', 'Gao, Xiaohu']",Sci Rep,,,True
0e2d510f5f9a78a65dbe34e78f2a3cda5adadb4f,PMC,A Universal Protein Tag for Delivery of SiRNA-Aptamer Chimeras,http://dx.doi.org/10.1038/srep03129,PMC3819613,24196104,CC BY-NC-SA,"siRNA-aptamer chimeras have emerged as one of the most promising approaches for targeted delivery of siRNA due to the modularity of their diblock RNA structure, relatively lower cost over other targeted delivery approaches, and, most importantly, the outstanding potential for clinical translation. However, additional challenges must be addressed for efficient RNA interference (RNAi), in particular, endosomal escape. Currently, vast majority of siRNA delivery vehicles are based on cationic materials, which form complexes with negatively charged siRNA. Unfortunately, these approaches complicate the formulations again by forming large complexes with heterogeneous sizes, unfavorable surface charges, colloidal instability, and poor targeting ligand orientation. Here, we report the development of a small and simple protein tag that complements the therapeutic and targeting functionalities of chimera with two functional domains: a dsRNA binding domain (dsRBD) for siRNA docking and a pH-dependent polyhistidine to disrupt endosomal membrane. The protein selectively tags along the siRNA block of individual chimera, rendering the overall size of the complex small, desirable for deep tissue penetration, and the aptamer block accessible for target recognition. More interestingly, we found that extending the c-terminal polyhistidine segment in the protein tag to 18 amino acids completely abolishes the RNA binding function of dsRBD.",2013 Nov 7,"['Liu, Hong Yan', 'Gao, Xiaohu']",Sci Rep,,,False
bf23011551b21af6538e43974e74e6078f538028,PMC,Mild infection of a novel H7N9 avian influenza virus in children in Shanghai,http://dx.doi.org/10.1038/emi.2013.41,PMC3820982,26038475,CC BY-NC-ND,,2013 Jul 10,"['Yu, Xuelian', 'Zhang, Xi', 'He, Yi', 'Wu, Huanyu', 'Gao, Xia', 'Pan, Qichao', 'Shen, Jiaren', 'Zhu, Jianming', 'Chen, Hongyou', 'Zhu, Yiyi', 'Wu, Fan', 'Wang, Jianwei', 'Yuan, Zhengan']",Emerg Microbes Infect,,,True
461bd946be4c4280c46eb9a7b163e9f3da0a734a,PMC,Reduction of influenza virus-induced lung inflammation and mortality in animals treated with a phosophodisestrase-4 inhibitor and a selective serotonin reuptake inhibitor,http://dx.doi.org/10.1038/emi.2013.52,PMC3821288,26038487,CC BY-NC-ND,"Inflammatory responses contribute to the morbidity and mortality of severe influenza. Current antiviral therapy offers limited success in treating severe influenza infection with both H1N1 and H5N1 viruses. We evaluated the effect of a neuraminidase inhibitor in combination with immunomodulatory drugs in vitro and in a mouse model of influenza A H1N1 infection by determining survival rate, lung inflammation markers and histopathology. Sertraline and rolipram significantly improved survival in mice infected with a lethal dose of influenza A H1N1 virus. Prophylactic treatment resulted in survival rates of 40% (rolipram), 30% (oseltamivir), 0% (sertraline), 100% (rolipram/oseltamivir) and 70% (sertraline/oseltamivir). Treatment in a therapeutic setting (24 h post-infection) resulted in 80% (rolipram/oseltamivir) and 40% (sertraline/oseltamivir) survival. Sertraline and rolipram had no effect on virus replication in vitro and in vivo, but significantly reduced lung inflammation. A significant reduction in cellular infiltration (10-fold) along with inflammatory cytokines monocyte chemotactic protein-1 (10-fold), interleukin-6 (5-fold) and regulated on activation normal T cell expressed and secreted (5-fold) was observed in the animals treated with the combination compared to oseltamivir alone. Lung histopathology of mice treated with combinations revealed significantly reduced consolidation, infiltration and alveolitis compared to oseltamivir alone. Rolipram and sertraline reduced H1N1 virus-induced lung inflammation and mortality. These data support further development of immunomodulatory agents for severe influenza.",2013 Aug 21,"['Sharma, Geeta', 'Champalal Sharma, Danilal', 'Hwei Fen, Leong', 'Pathak, Mukta', 'Bethur, Nijaguna', 'Pendharkar, Vishal', 'Peiris, Malik', 'Altmeyer, Ralf']",Emerg Microbes Infect,,,True
b9bca46e86a4f2ff88b88154c8db5ddbe9c329b9,PMC,Drugs to cure avian influenza infection – multiple ways to prevent cell death,http://dx.doi.org/10.1038/cddis.2013.367,PMC3824676,24091678,CC BY-NC-SA,"New treatments and new drugs for avian influenza virus (AIV) infection are developed continually, but there are still high mortality rates. The main reason may be that not all cell death pathways induced by AIV were blocked by the current therapies. In this review, drugs for AIV and associated acute respiratory distress syndrome (ARDS) are summarized. The roles of antioxidant (vitamin C) and multiple immunomodulators (such as Celecoxib, Mesalazine and Eritoran) are discussed. The clinical care of ARDS may result in ischemia reperfusion injury to poorly ventilated alveolar cells. Cyclosporin A should effectively inhibit this kind of damages and, therefore, may be the key drug for the survival of patients with virus-induced ARDS. Treatment with protease inhibitor Ulinastatin could also protect lysosome integrity after the infection. Through these analyses, a large drug combination is proposed, which may hypothetically greatly reduce the mortality rate.",2013 Oct 3,"Yuan, S",Cell Death Dis,,,True
2dfd4bdcf53215a88599651441351138f99089b6,PMC,The aging lung,http://dx.doi.org/10.2147/CIA.S51152,PMC3825547,24235821,CC BY-NC,"There are many age-associated changes in the respiratory and pulmonary immune system. These changes include decreases in the volume of the thoracic cavity, reduced lung volumes, and alterations in the muscles that aid respiration. Muscle function on a cellular level in the aging population is less efficient. The elderly population has less pulmonary reserve, and cough strength is decreased in the elderly population due to anatomic changes and muscle atrophy. Clearance of particles from the lung through the mucociliary elevator is decreased and associated with ciliary dysfunction. Many complex changes in immunity with aging contribute to increased susceptibility to infections including a less robust immune response from both the innate and adaptive immune systems. Considering all of these age-related changes to the lungs, pulmonary disease has significant consequences for the aging population. Chronic lower respiratory tract disease is the third leading cause of death in people aged 65 years and older. With a large and growing aging population, it is critical to understand how the body changes with age and how this impacts the entire respiratory system. Understanding the aging process in the lung is necessary in order to provide optimal care to our aging population. This review focuses on the nonpathologic aging process in the lung, including structural changes, changes in muscle function, and pulmonary immunologic function, with special consideration of obstructive lung disease in the elderly.",2013 Nov 6,"['Lowery, Erin M', 'Brubaker, Aleah L', 'Kuhlmann, Erica', 'Kovacs, Elizabeth J']",Clin Interv Aging,,,True
6f1014ef2ef3a31e4e58cad28dc625df3701ac42,PMC,Inflammation and Immune System Activation in Aging: A Mathematical Approach,http://dx.doi.org/10.1038/srep03254,PMC3832874,24247109,CC BY-NC-ND,"Memory and learning declines are consequences of normal aging. Since those functions are associated with the hippocampus, I analyzed the global gene expression data from post-mortem hippocampal tissue of 25 old (age ≥ 60 yrs) and 15 young (age ≤ 45 yrs) cognitively intact human subjects. By employing a rigorous, multi-method bioinformatic approach, I identified 36 genes that were the most significant in terms of differential expression; and by employing mathematical modeling, I demonstrated that 7 of the 36 genes were able to discriminate between the old and young subjects with high accuracy. Remarkably, 90% of the known genes from those 36 most significant genes are associated with either inflammation or immune system activation. This suggests that chronic inflammation and immune system over-activity may underlie the aging process of the human brain, and that potential anti-inflammatory treatments targeting those genes may slow down this process and alleviate its symptoms.",2013 Nov 19,"Nikas, Jason B.",Sci Rep,,,True
cd7d4669d8c2e2a4c8957f7c6ea4b809e506d96c,PMC,Inflammation and Immune System Activation in Aging: A Mathematical Approach,http://dx.doi.org/10.1038/srep03254,PMC3832874,24247109,CC BY-NC-ND,"Memory and learning declines are consequences of normal aging. Since those functions are associated with the hippocampus, I analyzed the global gene expression data from post-mortem hippocampal tissue of 25 old (age ≥ 60 yrs) and 15 young (age ≤ 45 yrs) cognitively intact human subjects. By employing a rigorous, multi-method bioinformatic approach, I identified 36 genes that were the most significant in terms of differential expression; and by employing mathematical modeling, I demonstrated that 7 of the 36 genes were able to discriminate between the old and young subjects with high accuracy. Remarkably, 90% of the known genes from those 36 most significant genes are associated with either inflammation or immune system activation. This suggests that chronic inflammation and immune system over-activity may underlie the aging process of the human brain, and that potential anti-inflammatory treatments targeting those genes may slow down this process and alleviate its symptoms.",2013 Nov 19,"Nikas, Jason B.",Sci Rep,,,False
be9b45f1ce1542eb6c30e86b966a33f53eaac419,PMC,Braess's Paradox in Epidemic Game: Better Condition Results in Less Payoff,http://dx.doi.org/10.1038/srep03292,PMC3836038,24256996,CC BY-NC-ND,"Facing the threats of infectious diseases, we take various actions to protect ourselves, but few studies considered an evolving system with competing strategies. In view of that, we propose an evolutionary epidemic model coupled with human behaviors, where individuals have three strategies: vaccination, self-protection and laissez faire, and could adjust their strategies according to their neighbors' strategies and payoffs at the beginning of each new season of epidemic spreading. We found a counter-intuitive phenomenon analogous to the well-known Braess's Paradox, namely a better condition may lead to worse performance. Specifically speaking, increasing the successful rate of self-protection does not necessarily reduce the epidemic size or improve the system payoff. The range and degree of the Braess's Paradox are sensitive to both the parameters characterizing the epidemic spreading and the strategy payoff, while the existence of the Braess's Paradox is insensitive to the network topologies. This phenomenon can be well explained by a mean-field approximation. Our study demonstrates an important fact that a better condition for individuals may yield a worse outcome for the society.",2013 Nov 21,"['Zhang, Hai-Feng', 'Yang, Zimo', 'Wu, Zhi-Xi', 'Wang, Bing-Hong', 'Zhou, Tao']",Sci Rep,,,True
a1ee35e61d7e3426ac64d379d82a1c9aa3d251a6,PMC,Braess's Paradox in Epidemic Game: Better Condition Results in Less Payoff,http://dx.doi.org/10.1038/srep03292,PMC3836038,24256996,CC BY-NC-ND,"Facing the threats of infectious diseases, we take various actions to protect ourselves, but few studies considered an evolving system with competing strategies. In view of that, we propose an evolutionary epidemic model coupled with human behaviors, where individuals have three strategies: vaccination, self-protection and laissez faire, and could adjust their strategies according to their neighbors' strategies and payoffs at the beginning of each new season of epidemic spreading. We found a counter-intuitive phenomenon analogous to the well-known Braess's Paradox, namely a better condition may lead to worse performance. Specifically speaking, increasing the successful rate of self-protection does not necessarily reduce the epidemic size or improve the system payoff. The range and degree of the Braess's Paradox are sensitive to both the parameters characterizing the epidemic spreading and the strategy payoff, while the existence of the Braess's Paradox is insensitive to the network topologies. This phenomenon can be well explained by a mean-field approximation. Our study demonstrates an important fact that a better condition for individuals may yield a worse outcome for the society.",2013 Nov 21,"['Zhang, Hai-Feng', 'Yang, Zimo', 'Wu, Zhi-Xi', 'Wang, Bing-Hong', 'Zhou, Tao']",Sci Rep,,,False
4c13be11a41de81fb7066f7993da218c463cfa1e,PMC,Specific Plasma Autoantibody Reactivity in Myelodysplastic Syndromes,http://dx.doi.org/10.1038/srep03311,PMC3837310,24264604,CC BY-NC-ND,"Increased autoantibody reactivity in plasma from Myelodysplastic Syndromes (MDS) patients may provide novel disease signatures, and possible early detection. In a two-stage study we investigated Immunoglobulin G reactivity in plasma from MDS, Acute Myeloid Leukemia post MDS patients, and a healthy cohort. In exploratory Stage I we utilized high-throughput protein arrays to identify 35 high-interest proteins showing increased reactivity in patient subgroups compared to healthy controls. In validation Stage II we designed new arrays focusing on 25 of the proteins identified in Stage I and expanded the initial cohort. We validated increased antibody reactivity against AKT3, FCGR3A and ARL8B in patients, which enabled sample classification into stable MDS and healthy individuals. We also detected elevated AKT3 protein levels in MDS patient plasma. The discovery of increased specific autoantibody reactivity in MDS patients, provides molecular signatures for classification, supplementing existing risk categorizations, and may enhance diagnostic and prognostic capabilities for MDS.",2013 Nov 22,"['Mias, George I.', 'Chen, Rui', 'Zhang, Yan', 'Sridhar, Kunju', 'Sharon, Donald', 'Xiao, Li', 'Im, Hogune', 'Snyder, Michael P.', 'Greenberg, Peter L.']",Sci Rep,,,True
b64600216303a5d0ba53a87405af547758a9e90a,PMC,Specific Plasma Autoantibody Reactivity in Myelodysplastic Syndromes,http://dx.doi.org/10.1038/srep03311,PMC3837310,24264604,CC BY-NC-ND,"Increased autoantibody reactivity in plasma from Myelodysplastic Syndromes (MDS) patients may provide novel disease signatures, and possible early detection. In a two-stage study we investigated Immunoglobulin G reactivity in plasma from MDS, Acute Myeloid Leukemia post MDS patients, and a healthy cohort. In exploratory Stage I we utilized high-throughput protein arrays to identify 35 high-interest proteins showing increased reactivity in patient subgroups compared to healthy controls. In validation Stage II we designed new arrays focusing on 25 of the proteins identified in Stage I and expanded the initial cohort. We validated increased antibody reactivity against AKT3, FCGR3A and ARL8B in patients, which enabled sample classification into stable MDS and healthy individuals. We also detected elevated AKT3 protein levels in MDS patient plasma. The discovery of increased specific autoantibody reactivity in MDS patients, provides molecular signatures for classification, supplementing existing risk categorizations, and may enhance diagnostic and prognostic capabilities for MDS.",2013 Nov 22,"['Mias, George I.', 'Chen, Rui', 'Zhang, Yan', 'Sridhar, Kunju', 'Sharon, Donald', 'Xiao, Li', 'Im, Hogune', 'Snyder, Michael P.', 'Greenberg, Peter L.']",Sci Rep,,,True
dab21bebc7d9ee2f77332c23b420280ee74772fd,PMC,Bovine respiratory syncytial virus: infection dynamics within and between herds,http://dx.doi.org/10.1136/vr.101936,PMC3841740,24158321,CC BY-NC,"The infection dynamics of bovine respiratory syncytial virus (BRSV) were studied in randomly selected Norwegian dairy herds. A total of 134 herds were tested twice, six months apart. The herds were classified as positive for BRSV if at least one animal between 150 and 365 days old tested positive for antibodies against BRSV, thereby representing herds that had most likely had the virus present during the previous year. The prevalence of positive herds at the first and second sampling was 34 per cent and at 41 per cent, respectively, but varied greatly between regions. Negative herds were found in close proximity to positive herds. Some of these herds remained negative despite several new infections nearby. Of the herds initially being negative, 42 per cent changed status to positive during the six months. This occurred at the same rate during summer as winter, but a higher rate of animals in the herds was positive if it took place during winter. Of the herds initially being positive, 33 per cent changed to negative. This indicates that an effective strategy to lower the prevalence and the impact of BRSV could be to employ close surveillance and place a high biosecurity focus on the negative herds.",2013 Nov 16,"['Klem, T. B.', 'Gulliksen, S. M.', 'Lie, K.-I.', 'Løken, T.', 'Østerås, O.', 'Stokstad, M.']",Vet Rec,,,True
b793841edbf590d90716ed93f6c7614d142c01ea,PMC,Aetiology of paediatric pneumonia after the introduction of pneumococcal conjugate vaccine,http://dx.doi.org/10.1183/09031936.00199112,PMC3844138,23598951,CC BY-NC,"We describe the aetiology of community-acquired pneumonia in children before and after the introduction of the pneumococcal conjugate vaccination (PCV) programme in 2006. Prospective studies were conducted in 2001–2002 (pre-vaccine) and 2009–2011 (post-vaccine) of children aged 0–16 years with radiologically confirmed pneumonia seen in hospital. Investigations included culture, serology, immunofluorescence antibody and urine antigen testing, with an increased use of PCR assays and expanded panels of pathogens in the post-vaccine study. 241 and 160 children were enrolled in the pre- and post-vaccine studies, respectively (73% aged <5 years). Identification of a causative pathogen was higher post-vaccination (61%) than pre-vaccination (48.5%) (p=0.019). Rates of bacterial infections were not different between post- and pre-vaccine studies (17.5% versus 24%, p=0.258). Viral (31%) and mixed (12.5%) infections were found more often post-vaccination (19.5%, p=0.021) than pre-vaccination (5%, p=0.015). Rates of identified pneumococcal infections were comparable between pre- and post-vaccine studies (14.7% versus 17.4%, p=0.557). Diagnosis of pneumococcal infection post-vaccination improved when PCR was used compared to culture (21.6% versus 6%, p=0.0004). Serotypes included in PCV13 but not PCV7 were identified in 75% (18 out of 24) post-vaccination. Infection with nonvaccine pneumococcal serotypes continues to be a significant cause of pneumonia in children in the UK.",2013 Dec 18,"['Elemraid, Mohamed A.', 'Sails, Andrew D.', 'Eltringham, Gary J.A.', 'Perry, John D.', 'Rushton, Stephen P.', 'Spencer, David A.', 'Thomas, Matthew F.', 'Eastham, Katherine M.', 'Hampton, Fiona', 'Gennery, Andrew R.', 'Clark, Julia E.']",Eur Respir J,,,True
572d73abf2ddec90f9a3d8888fbdc3671aea242b,PMC,How to Manage a Public Health Crisis and Bioterrorism in Korea,http://dx.doi.org/10.1016/j.phrp.2013.09.010,PMC3845231,24298436,CC BY-NC,,2013 Oct,"['Cho, Hae-Wol', 'Chu, Chaeshin']",Osong Public Health Res Perspect,,,False
c2b5f16729c3dd1b356b0d25814d039192d0c9e5,PMC,Public Health Crisis Preparedness and Response in Korea,http://dx.doi.org/10.1016/j.phrp.2013.09.008,PMC3845460,24298444,CC BY-NC,"Since the 2006 Pandemic Influenza Preparedness and Response Plan according to the World Health Organization’s recommendation, the Republic of Korea has prepared and periodically evaluated the plan to respond to various public health crises including pandemic influenza. Korea has stockpiled 13,000,000 doses of antiviral drugs covering 26% of the Korean population and runs 519 isolated beds in 16 medical institutions. The division of public health crisis response in Korea Centers for Disease Control and Prevention are in charge of responding to public health crises caused by emerging infectious diseases including severe acute respiratory syndrome, avian influenza human infection, and pandemic influenza. Its job description includes preparing for emerging infectious diseases, securing medical resources during a crisis, activating the emergency response during the crisis, and fortification of capabilities of public health personnel. It could evolve into a comprehensive national agency to deal with public health crisis based on the experience of previous national emerging infectious diseases.",2013 Oct,"['Lee, Hye-Young', 'Oh, Mi-Na', 'Park, Yong-Shik', 'Chu, Chaeshin', 'Son, Tae-Jong']",Osong Public Health Res Perspect,,,False
30d2d2d37c2a884db55ab21d1cbd92abcff95fa2,PMC,Effect of hepatocyte growth factor and angiotensin II on rat cardiomyocyte hypertrophy,http://dx.doi.org/10.1590/S0100-879X2012007500159,PMC3854218,23044624,CC BY-NC,"Angiotensin II (Ang II) plays an important role in cardiomyocyte hypertrophy. The combined effect of hepatocyte growth factor (HGF) and Ang II on cardiomyocytes is unknown. The present study was designed to determine the effect of HGF on cardiomyocyte hypertrophy and to explore the combined effect of HGF and Ang II on cardiomyocyte hypertrophy. Primary cardiomyocytes were isolated from neonatal rat hearts and cultured in vitro. Cells were treated with Ang II (1 µM) alone, HGF (10 ng/mL) alone, and Ang II (1 µM) plus HGF (10 ng/mL) for 24, 48, and 72 h. The amount of [(3)H]-leucine incorporation was then measured to evaluate protein synthesis. The mRNA levels of β-myosin heavy chain and atrial natriuretic factor were determined by real-time PCR to evaluate the presence of fetal phenotypes of gene expression. The cell size of cardiomyocytes was also studied. Ang II (1 µM) increased cardiomyocyte hypertrophy. Similar to Ang II, treatment with 1 µM HGF promoted cardiomyocyte hypertrophy. Moreover, the combination of 1 µM Ang II and 10 ng/mL HGF clearly induced a combined pro-hypertrophy effect on cardiomyocytes. The present study demonstrates for the first time a novel, combined effect of HGF and Ang II in promoting cardiomyocyte hypertrophy.",2012 Oct 15,"['Chen, Ai-Lan', 'Ou, Cai-Wen', 'He, Zhao-Chu', 'Liu, Qi-Cai', 'Dong, Qi', 'Chen, Min-Sheng']",Braz J Med Biol Res,,,True
92dc5a63d0776632f789e874bb0217c4ac1d021b,PMC,Coping with genetic diversity: the contribution of pathogen and human genomics to modern vaccinology,http://dx.doi.org/10.1590/S0100-879X2011007500142,PMC3854287,22030866,CC BY-NC,"Vaccine development faces major difficulties partly because of genetic variation in both infectious organisms and humans. This causes antigenic variation in infectious agents and a high interindividual variability in the human response to the vaccine. The exponential growth of genome sequence information has induced a shift from conventional culture-based to genome-based vaccinology, and allows the tackling of challenges in vaccine development due to pathogen genetic variability. Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. Accumulating results provide evidence for the existence of a number of genes involved in protective immune responses that are induced either by natural infections or vaccines. Variation in immune responses could be viewed as the result of a perturbation of gene networks; this should help in understanding how a particular polymorphism or a combination thereof could affect protective immune responses. Here we will present: i) the first genome-based vaccines that served as proof of concept, and that provided new critical insights into vaccine development strategies; ii) an overview of genetic predisposition in infectious diseases and genetic control in responses to vaccines; iii) population genetic differences that are a rationale behind group-targeted vaccines; iv) an outlook for genetic control in infectious diseases, with special emphasis on the concept of molecular networks that will provide a structure to the huge amount of genomic data.",2011 Oct 28,"['Lemaire, D.', 'Barbosa, T.', 'Rihet, P.']",Braz J Med Biol Res,,,True
dcf7e06f01308a2d2d081e7596471d650d181dc9,PMC,Research Resource: Identification of Novel Growth Hormone-Regulated Phosphorylation Sites by Quantitative Phosphoproteomics,http://dx.doi.org/10.1210/me.2011-1258,PMC3858665,22570334,CC BY-NC,"GH and GH receptors are expressed throughout life, and GH elicits a diverse range of responses, including growth and altered metabolism. It is therefore important to understand the full spectrum of GH signaling pathways and cellular responses. We applied mass spectrometry-based phosphoproteomics combined with stable isotope labeling with amino acids in cell culture to identify proteins rapidly phosphorylated in response to GH in 3T3-F442A preadipocytes. We identified 132 phosphosites in 95 proteins that exhibited rapid (5 or 15 min) GH-dependent statistically significant increases in phosphorylation by more than or equal to 50% and 96 phosphosites in 46 proteins that were down-regulated by GH by more than or equal to 30%. Several of the GH-stimulated phosphorylation sites were known (e.g. regulatory Thr/Tyr in Erks 1 and 2, Tyr in signal transducers and activators of transcription (Stat) 5a and 5b, Ser939 in tuberous sclerosis protein (TSC) 2 or tuberin). The remaining 126 GH-stimulated sites were not previously associated with GH. Kyoto Encyclopedia of Genes and Genomes pathway analysis of GH-stimulated sites indicated enrichment in proteins associated with the insulin and mammalian target of rapamycin (mTOR) pathways, regulation of the actin cytoskeleton, and focal adhesions. Akt/protein kinase A consensus sites (RXRXXS/T) were the most commonly phosphorylated consensus sites. Immunoblotting confirmed GH-stimulated phosphorylation of all seven novel GH-dependent sites tested [regulatory sites in proline-rich Akt substrate, 40 kDA (PRAS40), regulatory associated protein of mTOR, ATP-citrate lyase, Na(+)/H(+) exchanger-1, N-myc downstream regulated gene 1, and Shc]). The immunoblot results suggest that many, if not most, of the GH-stimulated phosphosites identified in this large-scale quantitative phosphoproteomics analysis, including sites in multiple proteins in the Akt/ mTOR complex 1 pathway, are phosphorylated in response to GH. Their identification significantly broadens our thinking of GH-regulated cell functions.",2012 Jun 8,"['Ray, Bridgette N.', 'Kweon, Hye Kyong', 'Argetsinger, Lawrence S.', 'Fingar, Diane C.', 'Andrews, Philip C.', 'Carter-Su, Christin']",Mol Endocrinol,,,False
71edbd57cdd9af956a12054932e0cbdb87ce1fea,PMC,Social Network Characteristics and Body Mass Index in an Elderly Korean Population,http://dx.doi.org/10.3961/jpmph.2013.46.6.336,PMC3859855,24349655,CC BY-NC,"OBJECTIVES: Research has shown that obesity appears to spread through social ties. However, the association between other characteristics of social networks and obesity is unclear. This study aimed to identify the association between social network characteristics and body mass index (BMI, kg/m(2)) in an elderly Korean population. METHODS: This cross-sectional study analyzed data from 657 Koreans (273 men, 384 women) aged 60 years or older who participated in the Korean Social Life, Health, and Aging Project. Network size is a count of the number of friends. Density of communication network is the number of connections in the social network reported as a fraction of the total links possible in the personal (ego-centric) network. Average frequency of communication (or meeting) measures how often network members communicate (or meet) each other. The association of each social network measure with BMI was investigated by multiple linear regression analysis. RESULTS: After adjusting for potential confounders, the men with lower density (<0.71) and higher network size (4-6) had the higher BMI (β=1.089, p=0.037) compared to the men with higher density (>0.83) and lower size (1-2), but not in the women (p=0.393). The lowest tertile of communication frequency was associated with higher BMI in the women (β=0.885, p=0.049), but not in the men (p=0.140). CONCLUSIONS: Our study suggests that social network structure (network size and density) and activation (communication frequency and meeting frequency) are associated with obesity among the elderly. There may also be gender differences in this association.",2013 Nov 28,"['Lee, Won Joon', 'Youm, Yoosik', 'Rhee, Yumie', 'Park, Yeong-Ran', 'Chu, Sang Hui', 'Kim, Hyeon Chang']",J Prev Med Public Health,,,True
84e8e0300802fb315520524a718492573ad79432,PMC,"Factors influencing Dipylidium sp. infection in a free-ranging social carnivore, the spotted hyaena (Crocuta crocuta)()",http://dx.doi.org/10.1016/j.ijppaw.2013.09.003,PMC3862517,24533344,CC BY-NC-ND,"We provide the first genetic sequence data for a Dipylidium species from a wild carnivore plus an analysis of the effects of ecological, demographic, physiological and behavioural factors on Dipylidium sp. infection prevalence in a social carnivore, the spotted hyaena (Crocuta crocuta), in the Serengeti National Park, Tanzania. Our sequence data from a mitochondrial gene fragment (1176 base pair long) had a similarity of between 99% and 89% to Dipylidium caninum. We determined infection prevalence in 146 faecal samples from 124 known animals in three social groups (termed clans) using molecular screening and Dipylidium proglottid presence. Our analysis revealed significantly higher infection prevalence in juveniles (55%) than adults (15.8%), indicating that predominantly juveniles maintained infection in clans. The likelihood of infection in juveniles significantly: (1) increased as the number of adults and older juveniles (>6 months) at communal dens increased, implying a positive relationship between this factor and the size of the intermediate host (probably a flea species) population at communal dens; (2) decreased as the number of younger juveniles (<6 months) increased, suggesting that the chance of susceptible juveniles ingesting infected fleas during self-grooming declined as the number of infected fleas per younger juvenile declined; and (3) decreased during periods of low prey abundance in clan territories when an increased reliance on long-distances foraging excursions reduces the number of clan members visiting communal dens, possibly resulting in a decline in flea populations at dens. Long-distance foraging also increases the intervals (in days) between nursing visits by lactating females to their offspring. Lengthy intervals between milk intake by infected juveniles may reduce adult Dipylidium fecundity and hence decrease infection prevalence in the den flea population. Our study provides useful insights into Dipylidium epidemiology in a social carnivore population subject to large fluctuations in prey abundance.",2013 Sep 18,"['East, Marion L.', 'Kurze, Christoph', 'Wilhelm, Kerstin', 'Benhaiem, Sarah', 'Hofer, Heribert']",Int J Parasitol Parasites Wildl,,,False
67a52569919632f4bf58782538ff24838ac7f26c,PMC,miRNomes of haematopoietic stem cells and dendritic cells identify miR-30b as a regulator of Notch1,http://dx.doi.org/10.1038/ncomms3903,PMC3863901,24309499,CC BY-NC-SA,"Dendritic cells (DCs) are critical to initiate the immune response and maintain tolerance, depending on different status and subsets. The expression profiles of microRNAs (miRNAs) in various DC subsets and haematopoietic stem cells (HSCs), which generate DCs, remain to be fully identified. Here we examine miRNomes of mouse bone marrow HSCs, immature DCs, mature DCs and IL-10/NO-producing regulatory DCs by deep sequencing. We identify numerous stage-specific miRNAs and histone modification in HSCs and DCs at different differentiation stages. miR-30b, significantly upregulated via a TGF-beta/Smad3-mediated epigenetic pathway in regulatory DCs, can target Notch1 to promote IL-10 and NO production, suggesting that miR-30b is a negative regulator of immune response. We also identify miRNomes of in vivo counterparts of mature DCs and regulatory DCs and systematically compare them with DCs cultured in vitro. These results provide a resource for studying roles of miRNAs in stem cell biology, development and functional regulation of DC subsets.",2013 Dec 6,"['Su, Xiaoping', 'Qian, Cheng', 'Zhang, Qian', 'Hou, Jin', 'Gu, Yan', 'Han, Yanmei', 'Chen, Yongjian', 'Jiang, Minghong', 'Cao, Xuetao']",Nat Commun,,,True
584cc1bed26e74196a0a2396197de24d4509d4b0,PMC,miRNomes of haematopoietic stem cells and dendritic cells identify miR-30b as a regulator of Notch1,http://dx.doi.org/10.1038/ncomms3903,PMC3863901,24309499,CC BY-NC-SA,"Dendritic cells (DCs) are critical to initiate the immune response and maintain tolerance, depending on different status and subsets. The expression profiles of microRNAs (miRNAs) in various DC subsets and haematopoietic stem cells (HSCs), which generate DCs, remain to be fully identified. Here we examine miRNomes of mouse bone marrow HSCs, immature DCs, mature DCs and IL-10/NO-producing regulatory DCs by deep sequencing. We identify numerous stage-specific miRNAs and histone modification in HSCs and DCs at different differentiation stages. miR-30b, significantly upregulated via a TGF-beta/Smad3-mediated epigenetic pathway in regulatory DCs, can target Notch1 to promote IL-10 and NO production, suggesting that miR-30b is a negative regulator of immune response. We also identify miRNomes of in vivo counterparts of mature DCs and regulatory DCs and systematically compare them with DCs cultured in vitro. These results provide a resource for studying roles of miRNAs in stem cell biology, development and functional regulation of DC subsets.",2013 Dec 6,"['Su, Xiaoping', 'Qian, Cheng', 'Zhang, Qian', 'Hou, Jin', 'Gu, Yan', 'Han, Yanmei', 'Chen, Yongjian', 'Jiang, Minghong', 'Cao, Xuetao']",Nat Commun,,,False
4001d5a0e4343f3d709850d95863466e3f7666ff,PMC,Journal Watch,http://dx.doi.org/10.1128/jmbe.v14i2.676,PMC3867778,,CC BY-NC-SA,,2013 Dec 2,,J Microbiol Biol Educ,,,False
1685a03eac1fe5f949aa6b7889e02dadf9d3f90f,PMC,"Identification of RNase L-Dependent, 3′-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells",http://dx.doi.org/10.1128/mBio.00698-13,PMC3870239,24255120,CC BY-NC-SA,"Small RNAs play a critical role in host-pathogen interaction. Indeed, small RNA-mediated silencing or RNA interference (RNAi) is one of the earliest forms of antiviral immunity. Although it represents the main defense system against viruses in many organisms, the antiviral role of RNAi has not been clearly proven in higher vertebrates. However, it is well established that their response to viral infection relies on the recognition of viral RNAs by host pattern recognition receptors (PRRs) to trigger activation of the interferon pathway. In the present work, we report the existence of a novel small noncoding RNA population produced in mammalian cells upon RNA virus infection. Using Sindbis virus (SINV) as a prototypic arbovirus model, we profiled the small RNA population of infected cells in both human and African green monkey cell lines. Here, we provide evidence for the presence of discrete small RNAs of viral origin that are not associated with the RNA-induced silencing complex (RISC), that are highly expressed and detected by Northern blot analysis, and that accumulate as 21- to 28-nucleotide (nt) species during infection. We report that the cellular antiviral endoribonuclease RNase L cleaves the viral genome, producing in turn the small RNAs. Surprisingly, we uncovered the presence of a modification on the 3′-end nucleotide of SINV-derived viral small RNAs (SvsRNAs) that might be at the origin of their stability. Altogether, our findings show that stable modified small viral RNAs could represent a novel way to modulate host-virus interaction upon SINV infection.",2013 Nov 19,"['Girardi, Erika', 'Chane-Woon-Ming, Béatrice', 'Messmer, Mélanie', 'Kaukinen, Pasi', 'Pfeffer, Sébastien']",mBio,,,True
5b96fac306b9b57121152798668506aabb688cac,PMC,How the Double Spherules of Infectious Bronchitis Virus Impact Our Understanding of RNA Virus Replicative Organelles,http://dx.doi.org/10.1128/mBio.00987-13,PMC3870251,24345746,CC BY-NC-SA,"Powered by advances in electron tomography, recent studies have extended our understanding of how viruses construct “replication factories” inside infected cells. Their function, however, remains an area of speculation with important implications for human health. It is clear from these studies that whatever their purpose, organelle structure is dynamic (M. Ulasli, M. H. Verheije, C. A. de Haan, and F. Reggiori, Cell. Microbiol. 12:844-861, 2010) and intricate (K. Knoops, M. Kikkert, S. H. Worm, J. C. Zevenhoven-Dobbe, Y. van der Meer, et al., PLOS Biol. 6:e226, 2008). But by concentrating on medically important viruses, these studies have failed to take advantage of the genetic variation inherent in a family of viruses that is as diverse as the archaea, bacteria, and eukaryotes combined (C. Lauber, J. J. Goeman, M. del Carmen Parquet, P. T. Nga, E. J. Snijder, et al., PLOS Pathog. 9:e1003500, 2013). In this climate, Maier et al. (H. J. Maier, P. C. Hawes, E. M. Cottam, J. Mantell, P. Verkade, et al., mBio 4:e00801-13, 2013) explored the replicative structures formed by an avian coronavirus that appears to have diverged at an early point in coronavirus evolution and shed light on controversial aspects of viral biology.",2013 Dec 17,"Neuman, Benjamin W.",mBio,,,True
972a4e182f215c25fe41c9e0716a2f14ffd2ed9c,PMC,Silent geographical spread of the H7N9 virus by online knowledge analysis of the live bird trade with a distributed focused crawler,http://dx.doi.org/10.1038/emi.2013.91,PMC3880875,26038450,CC BY-NC-SA,"Unlike those infected by H5N1, birds infected by the newly discovered H7N9 virus have no observable clinical symptoms. Public health workers in China do not know where the public health threat lies. In this study, we used a distributed focused crawler to analyze online knowledge of the live bird trade in first-wave provinces, namely, Jiangsu, Zhejiang, Anhui, and Shanghai, to track the new H7N9 virus and predict its spread. Of the 18 provinces proposed to be at high risk of infection, 10 reported human infections and one had poultry specimens that tested positive. Five provinces (Xinjiang, Yunnan, Guizhou, Shaanxi, and Tibet) as well as Hong Kong, Macao, and Taiwan were proposed to have no risk of H7N9 virus infection from the live bird trade. These data can help health authorities and the public to respond rapidly to reduce damage related to the spread of the virus.",2013 Dec 18,"['Chen, Chen', 'Lu, Shan', 'Du, Pengcheng', 'Wang, Haiyin', 'Yu, Weiwen', 'Song, Huawen', 'Xu, Jianguo']",Emerg Microbes Infect,,,True
b399652f894cc2c694e95c0ead64bdfae777318d,PMC,Silent geographical spread of the H7N9 virus by online knowledge analysis of the live bird trade with a distributed focused crawler,http://dx.doi.org/10.1038/emi.2013.91,PMC3880875,26038450,CC BY-NC-SA,"Unlike those infected by H5N1, birds infected by the newly discovered H7N9 virus have no observable clinical symptoms. Public health workers in China do not know where the public health threat lies. In this study, we used a distributed focused crawler to analyze online knowledge of the live bird trade in first-wave provinces, namely, Jiangsu, Zhejiang, Anhui, and Shanghai, to track the new H7N9 virus and predict its spread. Of the 18 provinces proposed to be at high risk of infection, 10 reported human infections and one had poultry specimens that tested positive. Five provinces (Xinjiang, Yunnan, Guizhou, Shaanxi, and Tibet) as well as Hong Kong, Macao, and Taiwan were proposed to have no risk of H7N9 virus infection from the live bird trade. These data can help health authorities and the public to respond rapidly to reduce damage related to the spread of the virus.",2013 Dec 18,"['Chen, Chen', 'Lu, Shan', 'Du, Pengcheng', 'Wang, Haiyin', 'Yu, Weiwen', 'Song, Huawen', 'Xu, Jianguo']",Emerg Microbes Infect,,,False
bd25781927e8eb5b121981ac6081cde159606c83,PMC,Successful Rechallenge with Imatinib in a Patient with Chronic Myeloid Leukemia Who Previously Experienced Imatinib Mesylate Induced Pneumonitis,http://dx.doi.org/10.4046/trd.2013.75.6.256,PMC3884114,24416057,CC BY-NC,"Imatinib mesylate is a targeted therapy that acts by inhibiting tyrosine kinase of the bcr-abl fusion oncoprotein, which is specific to chronic myeloid leukemia (CML), and the c-transmembrane receptor, which is specific to gastrointestinal stromal tumors. Interstitial pneumonitis is a rare adverse event of imatinib therapy. It is clinically difficult to distinguish from infectious pneumonia, which can frequently occur due to the underlying disease. The standard treatment for imatinib-induced pneumonitis is to discontinue the medication and optionally administer corticosteroids. However, there are a few cases of successful retrial with imatinib. We describe a case of successful rechallenge of imatinib in a patient with imatinib-induced interstitial pneumonitis and CML without a recurrence of the underlying disease after 3 months of follow-up.",2013 Dec 24,"['Go, Seong Woo', 'Kim, Boo Kyeong', 'Lee, Sung Hak', 'Kim, Tae-Jung', 'Huh, Joo Yeon', 'Lee, Jong Min', 'Hah, Jick Hwan', 'Kim, Dong Whi', 'Cho, Min Jung', 'Kim, Tae Wan', 'Kang, Ji Young']",Tuberc Respir Dis (Seoul),,,True
c6b4bc9d758eb2542292da9540b16861b6e1b023,PMC,Molecular analysis of sarcoidosis lymph nodes for microorganisms: a case–control study with clinical correlates,http://dx.doi.org/10.1136/bmjopen-2013-004065,PMC3884606,24366580,CC BY-NC,"INTRODUCTION: Sarcoidosis is an incurable, chronic granulomatous disease primarily involving the lungs and lymph nodes of unknown aetiology, treated with non-specific anti-inflammatory/immunosuppressive drugs. Persistently symptomatic patients worsen with a disabling, potentially fatal clinical course. To determine a possible infectious cause, we correlated in a case-control study the clinical information with the presence of bacterial DNA in sarcoidosis mediastinal lymph nodes compared with control lymph nodes resected during cancer surgery. METHODS: We retrospectively studied formalin-fixed, paraffin-embedded, mediastinal lymph nodes from 30 patients with sarcoidosis and 30 control patients with lung cancer. Nucleic acids were extracted from nodes, evaluated by ribosomal RNA PCR for bacterial 16S ribosomal DNA and the results were sequenced and compared with a bacterial sequence library. Clinical information was correlated. RESULTS: 11/30 (36.7%) of lymph nodes from patients with sarcoidosis had detectable bacterial DNA, significantly more than control patient lymph nodes (2/30, 6.7%), p=0.00516. At presentation, 19/30 (63.3%) patients with sarcoidosis were symptomatic including all patients with detectable bacterial DNA. Radiographically, there were 18 stage I and 12 stage II patients. All stage II patients were symptomatic and 75% had PCR-detectable bacteria. After a mean follow-up of 52.8±32.8 months, all patients with PCR-detectable bacteria in this series were persistently symptomatic requiring treatment. DISCUSSION: 36.6% of patients with sarcoidosis had detectable bacterial DNA on presentation, all of these patients were quite symptomatic and most were radiographically advanced stage II. These findings suggest that bacterial DNA-positive, symptomatic patients have more aggressive sarcoidosis that persists long term and might benefit from antimicrobial treatment directed against this presumed chronic granulomatous infection.",2013 Dec 21,"['Robinson, Lary A', 'Smith, Prudence', 'SenGupta, Dhruba J', 'Prentice, Jennifer L', 'Sandin, Ramon L']",BMJ Open,,,True
9a494f17a77c5920be077ac59abc8a7546f4ee67,PMC,Molecular analysis of sarcoidosis lymph nodes for microorganisms: a case–control study with clinical correlates,http://dx.doi.org/10.1136/bmjopen-2013-004065,PMC3884606,24366580,CC BY-NC,"INTRODUCTION: Sarcoidosis is an incurable, chronic granulomatous disease primarily involving the lungs and lymph nodes of unknown aetiology, treated with non-specific anti-inflammatory/immunosuppressive drugs. Persistently symptomatic patients worsen with a disabling, potentially fatal clinical course. To determine a possible infectious cause, we correlated in a case-control study the clinical information with the presence of bacterial DNA in sarcoidosis mediastinal lymph nodes compared with control lymph nodes resected during cancer surgery. METHODS: We retrospectively studied formalin-fixed, paraffin-embedded, mediastinal lymph nodes from 30 patients with sarcoidosis and 30 control patients with lung cancer. Nucleic acids were extracted from nodes, evaluated by ribosomal RNA PCR for bacterial 16S ribosomal DNA and the results were sequenced and compared with a bacterial sequence library. Clinical information was correlated. RESULTS: 11/30 (36.7%) of lymph nodes from patients with sarcoidosis had detectable bacterial DNA, significantly more than control patient lymph nodes (2/30, 6.7%), p=0.00516. At presentation, 19/30 (63.3%) patients with sarcoidosis were symptomatic including all patients with detectable bacterial DNA. Radiographically, there were 18 stage I and 12 stage II patients. All stage II patients were symptomatic and 75% had PCR-detectable bacteria. After a mean follow-up of 52.8±32.8 months, all patients with PCR-detectable bacteria in this series were persistently symptomatic requiring treatment. DISCUSSION: 36.6% of patients with sarcoidosis had detectable bacterial DNA on presentation, all of these patients were quite symptomatic and most were radiographically advanced stage II. These findings suggest that bacterial DNA-positive, symptomatic patients have more aggressive sarcoidosis that persists long term and might benefit from antimicrobial treatment directed against this presumed chronic granulomatous infection.",2013 Dec 21,"['Robinson, Lary A', 'Smith, Prudence', 'SenGupta, Dhruba J', 'Prentice, Jennifer L', 'Sandin, Ramon L']",BMJ Open,,,True
52af18e65c30ab487774ff99f7af93ebcb65154d,PMC,Molecular analysis of sarcoidosis lymph nodes for microorganisms: a case–control study with clinical correlates,http://dx.doi.org/10.1136/bmjopen-2013-004065,PMC3884606,24366580,CC BY-NC,"INTRODUCTION: Sarcoidosis is an incurable, chronic granulomatous disease primarily involving the lungs and lymph nodes of unknown aetiology, treated with non-specific anti-inflammatory/immunosuppressive drugs. Persistently symptomatic patients worsen with a disabling, potentially fatal clinical course. To determine a possible infectious cause, we correlated in a case-control study the clinical information with the presence of bacterial DNA in sarcoidosis mediastinal lymph nodes compared with control lymph nodes resected during cancer surgery. METHODS: We retrospectively studied formalin-fixed, paraffin-embedded, mediastinal lymph nodes from 30 patients with sarcoidosis and 30 control patients with lung cancer. Nucleic acids were extracted from nodes, evaluated by ribosomal RNA PCR for bacterial 16S ribosomal DNA and the results were sequenced and compared with a bacterial sequence library. Clinical information was correlated. RESULTS: 11/30 (36.7%) of lymph nodes from patients with sarcoidosis had detectable bacterial DNA, significantly more than control patient lymph nodes (2/30, 6.7%), p=0.00516. At presentation, 19/30 (63.3%) patients with sarcoidosis were symptomatic including all patients with detectable bacterial DNA. Radiographically, there were 18 stage I and 12 stage II patients. All stage II patients were symptomatic and 75% had PCR-detectable bacteria. After a mean follow-up of 52.8±32.8 months, all patients with PCR-detectable bacteria in this series were persistently symptomatic requiring treatment. DISCUSSION: 36.6% of patients with sarcoidosis had detectable bacterial DNA on presentation, all of these patients were quite symptomatic and most were radiographically advanced stage II. These findings suggest that bacterial DNA-positive, symptomatic patients have more aggressive sarcoidosis that persists long term and might benefit from antimicrobial treatment directed against this presumed chronic granulomatous infection.",2013 Dec 21,"['Robinson, Lary A', 'Smith, Prudence', 'SenGupta, Dhruba J', 'Prentice, Jennifer L', 'Sandin, Ramon L']",BMJ Open,,,False
5f7bc4da553becc28ba03a2ac4a98133d4689adc,PMC,Management of Kawasaki disease,http://dx.doi.org/10.1136/archdischild-2012-302841,PMC3888612,24162006,CC BY-NC,"Kawasaki disease (KD) is an acute self-limiting inflammatory disorder, associated with vasculitis, affecting predominantly medium-sized arteries, particularly the coronary arteries. In developed countries KD is the commonest cause of acquired heart disease in childhood. The aetiology of KD remains unknown, and it is currently believed that one or more as yet unidentified infectious agents induce an intense inflammatory host response in genetically susceptible individuals. Genetic studies have identified several susceptibility genes for KD and its sequelae in different ethnic populations, including FCGR2A, CD40, ITPKC, FAM167A-BLK and CASP3, as well as genes influencing response to intravenous immunoglobulin (IVIG) and aneurysm formation such as FCGR3B, and transforming growth factor (TGF) β pathway genes. IVIG and aspirin are effective therapeutically, but recent clinical trials and meta-analyses have demonstrated that the addition of corticosteroids to IVIG is beneficial for the prevention of coronary artery aneurysms (CAA) in severe cases with highest risk of IVIG resistance. Outside of Japan, however, clinical scores to predict IVIG resistance perform suboptimally. Furthermore, the evidence base does not provide clear guidance on which corticosteroid regimen is most effective. Other therapies, including anti-TNFα, could also have a role for IVIG-resistant KD. Irrespective of these caveats, it is clear that therapy that reduces inflammation in acute KD, improves outcome. This paper summarises recent advances in the understanding of KD pathogenesis and therapeutics, and provides an approach for managing KD patients in the UK in the light of these advances.",2014 Jan 25,"['Eleftheriou, D', 'Levin, M', 'Shingadia, D', 'Tulloh, R', 'Klein, NJ', 'Brogan, PA']",Arch Dis Child,,,True
18aa7bfcf8b4dfcad03cf4836aaaa5345d6cfdc7,PMC,Development of a Positive-readout Mouse Model of siRNA Pharmacodynamics,http://dx.doi.org/10.1038/mtna.2013.63,PMC3889190,24253258,CC BY-NC-ND,"Development of RNAi-based therapeutics has the potential to revolutionize treatment options for a range of human diseases. However, as with gene therapy, a major barrier to progress is the lack of methods to achieve and measure efficient delivery for systemic administration. We have developed a positive-readout pharmacodynamic transgenic reporter mouse model allowing noninvasive real-time assessment of siRNA activity. The model combines a luciferase reporter gene under the control of regulatory elements from the lac operon of Escherichia coli. Introduction of siRNA targeting lac repressor results in increased luciferase expression in cells where siRNA is biologically active. Five founder luciferase-expressing and three founder Lac-expressing lines were generated and characterized. Mating of ubiquitously expressing luciferase and lac lines generated progeny in which luciferase expression was significantly reduced compared with the parental line. Administration of isopropyl β-D-1-thiogalactopyranoside either in drinking water or given intraperitoneally increased luciferase expression in eight of the mice examined, which fell rapidly when withdrawn. Intraperitoneal administration of siRNA targeting lac in combination with Lipofectamine 2000 resulted in increased luciferase expression in the liver while control nontargeting siRNA had no effect. We believe a sensitive positive readout pharmacodynamics reporter model will be of use to the research community in RNAi-based vector development.",2013 Nov 19,"['Stevenson, Mark', 'Carlisle, Robert', 'Davies, Ben', 'Preece, Chris', 'Hammett, Michelle', 'Liu, Wei-li', 'Fisher, Kerry David', 'Ryan, Amy', 'Scrable, Heidi', 'Seymour, Leonard William']",Mol Ther Nucleic Acids,,,True
955a11ffa21e8ea71e2dd4ed9b59ebc6a8990535,PMC,ESCRT regulates surface expression of the Kir2.1 potassium channel,http://dx.doi.org/10.1091/mbc.E13-07-0394,PMC3890348,24227888,CC BY-NC-SA,"Protein quality control (PQC) is required to ensure cellular health. PQC is recognized for targeting the destruction of defective polypeptides, whereas regulated protein degradation mechanisms modulate the concentration of specific proteins in concert with physiological demands. For example, ion channel levels are physiologically regulated within tight limits, but a system-wide approach to define which degradative systems are involved is lacking. We focus on the Kir2.1 potassium channel because altered Kir2.1 levels lead to human disease and Kir2.1 restores growth on low-potassium medium in yeast mutated for endogenous potassium channels. Using this system, first we find that Kir2.1 is targeted for endoplasmic reticulum–associated degradation (ERAD). Next a synthetic gene array identifies nonessential genes that negatively regulate Kir2.1. The most prominent gene family that emerges from this effort encodes members of endosomal sorting complex required for transport (ESCRT). ERAD and ESCRT also mediate Kir2.1 degradation in human cells, with ESCRT playing a more prominent role. Thus multiple proteolytic pathways control Kir2.1 levels at the plasma membrane.",2014 Jan 15,"['Kolb, Alexander R.', 'Needham, Patrick G.', 'Rothenberg, Cari', 'Guerriero, Christopher J.', 'Welling, Paul A.', 'Brodsky, Jeffrey L.']",Mol Biol Cell,,,True
459f95218942f624446533e21c9ab2775b8efce3,PMC,ESCRT regulates surface expression of the Kir2.1 potassium channel,http://dx.doi.org/10.1091/mbc.E13-07-0394,PMC3890348,24227888,CC BY-NC-SA,"Protein quality control (PQC) is required to ensure cellular health. PQC is recognized for targeting the destruction of defective polypeptides, whereas regulated protein degradation mechanisms modulate the concentration of specific proteins in concert with physiological demands. For example, ion channel levels are physiologically regulated within tight limits, but a system-wide approach to define which degradative systems are involved is lacking. We focus on the Kir2.1 potassium channel because altered Kir2.1 levels lead to human disease and Kir2.1 restores growth on low-potassium medium in yeast mutated for endogenous potassium channels. Using this system, first we find that Kir2.1 is targeted for endoplasmic reticulum–associated degradation (ERAD). Next a synthetic gene array identifies nonessential genes that negatively regulate Kir2.1. The most prominent gene family that emerges from this effort encodes members of endosomal sorting complex required for transport (ESCRT). ERAD and ESCRT also mediate Kir2.1 degradation in human cells, with ESCRT playing a more prominent role. Thus multiple proteolytic pathways control Kir2.1 levels at the plasma membrane.",2014 Jan 15,"['Kolb, Alexander R.', 'Needham, Patrick G.', 'Rothenberg, Cari', 'Guerriero, Christopher J.', 'Welling, Paul A.', 'Brodsky, Jeffrey L.']",Mol Biol Cell,,,True
cb690769762bb2fc4b4d9b898b03623b589fe8c1,PMC,Inflammasomes in antiviral immunity: clues for influenza vaccine development,http://dx.doi.org/10.7774/cevr.2014.3.1.5,PMC3890450,24427758,CC BY-NC,"Inflammasomes are cytosolic multiprotein complexes that sense microbial motifs or cellular stress and stimulate caspase-1-dependent cytokine secretion and cell death. Recently, it has become increasingly evident that both DNA and RNA viruses activate inflammasomes, which control innate and adaptive immune responses against viral infections. In addition, recent studies suggest that certain microbiota induce inflammasomes-dependent adaptive immunity against influenza virus infections. Here, we review recent advances in research into the role of inflammasomes in antiviral immunity.",2014 Jan 18,"['Yamazaki, Tatsuya', 'Ichinohe, Takeshi']",Clin Exp Vaccine Res,,,True
41a94f21d4dc3946e1377439a2a3880fb9d33776,PMC,EndoU is a novel regulator of AICD during peripheral B cell selection,http://dx.doi.org/10.1084/jem.20130648,PMC3892980,24344237,CC BY-NC-SA,"Balanced transmembrane signals maintain a competent peripheral B cell pool limited in self-reactive B cells that may produce pathogenic autoantibodies. To identify molecules regulating peripheral B cell survival and tolerance to self-antigens (Ags), a gene modifier screen was performed with B cells from CD22-deficient C57BL/6 (CD22(−/−[B6])) mice that undergo activation-induced cell death (AICD) and fail to up-regulate c-Myc expression after B cell Ag receptor ligation. Likewise, lysozyme auto-Ag–specific B cells in Ig(Tg) hen egg lysozyme (HEL) transgenic mice inhabit the spleen but undergo AICD after auto-Ag encounter. This gene modifier screen identified EndoU, a single-stranded RNA-binding protein of ancient origin, as a major regulator of B cell survival in both models. EndoU gene disruption prevents AICD and normalizes c-Myc expression. These findings reveal that EndoU is a critical regulator of an unexpected and novel RNA-dependent pathway controlling peripheral B cell survival and Ag responsiveness that may contribute to peripheral B cell tolerance.",2014 Jan 13,"['Poe, Jonathan C.', 'Kountikov, Evgueni I.', 'Lykken, Jacquelyn M.', 'Natarajan, Abirami', 'Marchuk, Douglas A.', 'Tedder, Thomas F.']",J Exp Med,,,True
76bbd67d210cfbd619123b103b0aa1966857b75a,PMC,Frequency of tuberculosis among diabetic patients in the People’s Republic of China,http://dx.doi.org/10.2147/TCRM.S38872,PMC3894144,24453491,CC BY-NC,"The People’s Republic of China has nearly the highest incidence of both diabetes mellitus (DM) and tuberculosis (TB) worldwide. DM increases the risk of TB by two to three times and adversely affects TB treatment outcomes. The increasing epidemic of DM in the People’s Republic of China is due to decreased physical activity, unhealthy diet, and obesity. Over the last 20 years, the excellent free China National Tuberculosis Program has been set up, and the “DOTS” (directly observed treatment + short-course chemotherapy) model for TB control has successfully reduced the burden of TB, but the disease is still a considerable problem. Given the high burden of TB and DM in the People’s Republic of China and the relationship between the two diseases, it is sensible to screen DM patients for TB. A bidirectional screening of the two diseases was conducted in the People’s Republic of China from 2011 to 2012, which identified a TB incidence in patients with DM of about 958 per 100,000. Here, we report the findings of our recent study on the incidence of TB among diabetic patients in the People’s Republic of China. The data agree with those of previous reports.",2014 Jan 10,"['Wang, Hong-Tian', 'Zhang, Jing', 'Ji, Ling-Chao', 'You, Shao-Hua', 'Bai, Yin', 'Dai, Wei', 'Wang, Zhong-Yuan']",Ther Clin Risk Manag,,,True
d12bc5a4eb0ce72c95fd2fba8d5768fcb6036833,PMC,Characterizing and controlling the inflammatory network during influenza A virus infection,http://dx.doi.org/10.1038/srep03799,PMC3896911,24445954,CC BY-NC-SA,"To gain insights into the pathogenesis of influenza A virus (IAV) infections, this study focused on characterizing the inflammatory network and identifying key proteins by combining high-throughput data and computational techniques. We constructed the cell-specific normal and inflammatory networks for H5N1 and H1N1 infections through integrating high-throughput data. We demonstrated that better discrimination between normal and inflammatory networks by network entropy than by other topological metrics. Moreover, we identified different dynamical interactions among TLR2, IL-1β, IL10 and NFκB between normal and inflammatory networks using optimization algorithm. In particular, good robustness and multistability of inflammatory sub-networks were discovered. Furthermore, we identified a complex, TNFSF10/HDAC4/HDAC5, which may play important roles in controlling inflammation, and demonstrated that changes in network entropy of this complex negatively correlated to those of three proteins: TNFα, NFκB and COX-2. These findings provide significant hypotheses for further exploring the molecular mechanisms of infectious diseases and developing control strategies.",2014 Jan 21,"['Jin, Suoqin', 'Li, Yuanyuan', 'Pan, Ruangang', 'Zou, Xiufen']",Sci Rep,,,True
d6e8f2abf8928e3b52ba19ff95a4919e3e2d5768,PMC,Characterizing and controlling the inflammatory network during influenza A virus infection,http://dx.doi.org/10.1038/srep03799,PMC3896911,24445954,CC BY-NC-SA,"To gain insights into the pathogenesis of influenza A virus (IAV) infections, this study focused on characterizing the inflammatory network and identifying key proteins by combining high-throughput data and computational techniques. We constructed the cell-specific normal and inflammatory networks for H5N1 and H1N1 infections through integrating high-throughput data. We demonstrated that better discrimination between normal and inflammatory networks by network entropy than by other topological metrics. Moreover, we identified different dynamical interactions among TLR2, IL-1β, IL10 and NFκB between normal and inflammatory networks using optimization algorithm. In particular, good robustness and multistability of inflammatory sub-networks were discovered. Furthermore, we identified a complex, TNFSF10/HDAC4/HDAC5, which may play important roles in controlling inflammation, and demonstrated that changes in network entropy of this complex negatively correlated to those of three proteins: TNFα, NFκB and COX-2. These findings provide significant hypotheses for further exploring the molecular mechanisms of infectious diseases and developing control strategies.",2014 Jan 21,"['Jin, Suoqin', 'Li, Yuanyuan', 'Pan, Ruangang', 'Zou, Xiufen']",Sci Rep,,,True
daa7e124a09a2e115e1280e4c31891db5a22b05d,PMC,Amphotericin B Increases Influenza A Virus Infection by Preventing IFITM3-Mediated Restriction,http://dx.doi.org/10.1016/j.celrep.2013.10.033,PMC3898084,24268777,CC BY-NC-ND,"The IFITMs inhibit influenza A virus (IAV) replication in vitro and in vivo. Here, we establish that the antimycotic heptaen, amphotericin B (AmphoB), prevents IFITM3-mediated restriction of IAV, thereby increasing viral replication. Consistent with its neutralization of IFITM3, a clinical preparation of AmphoB, AmBisome, reduces the majority of interferon’s protective effect against IAV in vitro. Mechanistic studies reveal that IFITM1 decreases host-membrane fluidity, suggesting both a possible mechanism for IFITM-mediated restriction and its negation by AmphoB. Notably, we reveal that mice treated with AmBisome succumbed to a normally mild IAV infection, similar to animals deficient in Ifitm3. Therefore, patients receiving antifungal therapy with clinical preparations of AmphoB may be functionally immunocompromised and thus more vulnerable to influenza, as well as other IFITM3-restricted viral infections.",2013 Nov 21,"['Lin, Tsai-Yu', 'Chin, Christopher\xa0R.', 'Everitt, Aaron\xa0R.', 'Clare, Simon', 'Perreira, Jill\xa0M.', 'Savidis, George', 'Aker, Aaron\xa0M.', 'John, Sinu\xa0P.', 'Sarlah, David', 'Carreira, Erick\xa0M.', 'Elledge, Stephen\xa0J.', 'Kellam, Paul', 'Brass, Abraham\xa0L.']",Cell Rep,,,False
74a50bcf30b8484ab04a58452bd9a5e04236f02a,PMC,Amphotericin B Increases Influenza A Virus Infection by Preventing IFITM3-Mediated Restriction,http://dx.doi.org/10.1016/j.celrep.2013.10.033,PMC3898084,24268777,CC BY-NC-ND,"The IFITMs inhibit influenza A virus (IAV) replication in vitro and in vivo. Here, we establish that the antimycotic heptaen, amphotericin B (AmphoB), prevents IFITM3-mediated restriction of IAV, thereby increasing viral replication. Consistent with its neutralization of IFITM3, a clinical preparation of AmphoB, AmBisome, reduces the majority of interferon’s protective effect against IAV in vitro. Mechanistic studies reveal that IFITM1 decreases host-membrane fluidity, suggesting both a possible mechanism for IFITM-mediated restriction and its negation by AmphoB. Notably, we reveal that mice treated with AmBisome succumbed to a normally mild IAV infection, similar to animals deficient in Ifitm3. Therefore, patients receiving antifungal therapy with clinical preparations of AmphoB may be functionally immunocompromised and thus more vulnerable to influenza, as well as other IFITM3-restricted viral infections.",2013 Nov 21,"['Lin, Tsai-Yu', 'Chin, Christopher\xa0R.', 'Everitt, Aaron\xa0R.', 'Clare, Simon', 'Perreira, Jill\xa0M.', 'Savidis, George', 'Aker, Aaron\xa0M.', 'John, Sinu\xa0P.', 'Sarlah, David', 'Carreira, Erick\xa0M.', 'Elledge, Stephen\xa0J.', 'Kellam, Paul', 'Brass, Abraham\xa0L.']",Cell Rep,,,False
19d4a8102c9c60c132a3c64b4ae0beadd0895559,PMC,Amphotericin B Increases Influenza A Virus Infection by Preventing IFITM3-Mediated Restriction,http://dx.doi.org/10.1016/j.celrep.2013.10.033,PMC3898084,24268777,CC BY-NC-ND,"The IFITMs inhibit influenza A virus (IAV) replication in vitro and in vivo. Here, we establish that the antimycotic heptaen, amphotericin B (AmphoB), prevents IFITM3-mediated restriction of IAV, thereby increasing viral replication. Consistent with its neutralization of IFITM3, a clinical preparation of AmphoB, AmBisome, reduces the majority of interferon’s protective effect against IAV in vitro. Mechanistic studies reveal that IFITM1 decreases host-membrane fluidity, suggesting both a possible mechanism for IFITM-mediated restriction and its negation by AmphoB. Notably, we reveal that mice treated with AmBisome succumbed to a normally mild IAV infection, similar to animals deficient in Ifitm3. Therefore, patients receiving antifungal therapy with clinical preparations of AmphoB may be functionally immunocompromised and thus more vulnerable to influenza, as well as other IFITM3-restricted viral infections.",2013 Nov 21,"['Lin, Tsai-Yu', 'Chin, Christopher\xa0R.', 'Everitt, Aaron\xa0R.', 'Clare, Simon', 'Perreira, Jill\xa0M.', 'Savidis, George', 'Aker, Aaron\xa0M.', 'John, Sinu\xa0P.', 'Sarlah, David', 'Carreira, Erick\xa0M.', 'Elledge, Stephen\xa0J.', 'Kellam, Paul', 'Brass, Abraham\xa0L.']",Cell Rep,,,False
f2b1074882bd3bdb8794c79fb4ab6fb72fbbf2ee,PMC,Calculating the burden of disease of avian-origin H7N9 infections in China,http://dx.doi.org/10.1136/bmjopen-2013-004189,PMC3902515,24441057,CC BY-NC,"OBJECTIVE: A total of 131 cases of avian-originated H7N9 infection have been confirmed in China mainland from February 2013 to May 2013. We calculated the overall burden of H7N9 cases in China as of 31 May 2013 to provide an example of comprehensive burden of disease in the 21st century from an acute animal-borne emerging infectious disease. DESIGN: We present an accurate and operable method for estimating the burden of H7N9 cases in China. The main drivers of economic loss were identified. Costs were broken down into direct (outpatient and inpatient examination and treatment) and indirect costs (cost of disability-adjusted life years (DALYs) and losses in the poultry industry), which were estimated based on field surveys and China statistical year book. SETTING: Models were applied to estimate the overall burden of H7N9 cases in China. PARTICIPANTS: 131 laboratory-confirmed H7N9 cases by 31 May 2013. OUTCOME MEASURE: Burden of H7N9 cases including direct and indirect losses. RESULTS: The total direct medical cost was ¥16 422 535 (US$2 627 606). The mean cost for each patient was ¥10 117 (US$1619) for mild patients, ¥139 323 (US$22 292) for severe cases without death and ¥205 976 (US$32 956) for severe cases with death. The total cost of DALYs was ¥17 356 561 (US$2 777 050). The poultry industry losses amounted to ¥7.75 billion (US$1.24 billion) in 10 affected provinces and ¥3.68 billion (USD$0.59 billion) in eight non-affected adjacent provinces. CONCLUSIONS: The huge poultry industry losses followed live poultry markets closing down and poultry slaughtering in some areas. Though the proportion of direct medical losses and DALYs losses in the estimate of H7N9 burden was small, the medical costs per case were extremely high (particularly for addressing the use of modern medical devices). A cost-effectiveness assessment for the intervention should be conducted in a future study.",2014 Jan 17,"['Qi, Xiaopeng', 'Jiang, Dong', 'Wang, Hongliang', 'Zhuang, Dafang', 'Ma, Jiaqi', 'Fu, Jingying', 'Qu, Jingdong', 'Sun, Yan', 'Yu, Shicheng', 'Meng, Yujie', 'Huang, Yaohuan', 'Xia, Lanfang', 'Li, Yingying', 'Wang, Yong', 'Wang, Guohua', 'Xu, Ke', 'Zhang, Qun', 'Wan, Ming', 'Su, Xuemei', 'Fu, Gang', 'Gao, George F']",BMJ Open,,,True
7da1a3651e1aba73bc607cf4aaa93105af0c2bf7,PMC,Calculating the burden of disease of avian-origin H7N9 infections in China,http://dx.doi.org/10.1136/bmjopen-2013-004189,PMC3902515,24441057,CC BY-NC,"OBJECTIVE: A total of 131 cases of avian-originated H7N9 infection have been confirmed in China mainland from February 2013 to May 2013. We calculated the overall burden of H7N9 cases in China as of 31 May 2013 to provide an example of comprehensive burden of disease in the 21st century from an acute animal-borne emerging infectious disease. DESIGN: We present an accurate and operable method for estimating the burden of H7N9 cases in China. The main drivers of economic loss were identified. Costs were broken down into direct (outpatient and inpatient examination and treatment) and indirect costs (cost of disability-adjusted life years (DALYs) and losses in the poultry industry), which were estimated based on field surveys and China statistical year book. SETTING: Models were applied to estimate the overall burden of H7N9 cases in China. PARTICIPANTS: 131 laboratory-confirmed H7N9 cases by 31 May 2013. OUTCOME MEASURE: Burden of H7N9 cases including direct and indirect losses. RESULTS: The total direct medical cost was ¥16 422 535 (US$2 627 606). The mean cost for each patient was ¥10 117 (US$1619) for mild patients, ¥139 323 (US$22 292) for severe cases without death and ¥205 976 (US$32 956) for severe cases with death. The total cost of DALYs was ¥17 356 561 (US$2 777 050). The poultry industry losses amounted to ¥7.75 billion (US$1.24 billion) in 10 affected provinces and ¥3.68 billion (USD$0.59 billion) in eight non-affected adjacent provinces. CONCLUSIONS: The huge poultry industry losses followed live poultry markets closing down and poultry slaughtering in some areas. Though the proportion of direct medical losses and DALYs losses in the estimate of H7N9 burden was small, the medical costs per case were extremely high (particularly for addressing the use of modern medical devices). A cost-effectiveness assessment for the intervention should be conducted in a future study.",2014 Jan 17,"['Qi, Xiaopeng', 'Jiang, Dong', 'Wang, Hongliang', 'Zhuang, Dafang', 'Ma, Jiaqi', 'Fu, Jingying', 'Qu, Jingdong', 'Sun, Yan', 'Yu, Shicheng', 'Meng, Yujie', 'Huang, Yaohuan', 'Xia, Lanfang', 'Li, Yingying', 'Wang, Yong', 'Wang, Guohua', 'Xu, Ke', 'Zhang, Qun', 'Wan, Ming', 'Su, Xuemei', 'Fu, Gang', 'Gao, George F']",BMJ Open,,,True
a75b137b6b4d1cf780d3d8a0c14ee53f42546ef4,PMC,Calculating the burden of disease of avian-origin H7N9 infections in China,http://dx.doi.org/10.1136/bmjopen-2013-004189,PMC3902515,24441057,CC BY-NC,"OBJECTIVE: A total of 131 cases of avian-originated H7N9 infection have been confirmed in China mainland from February 2013 to May 2013. We calculated the overall burden of H7N9 cases in China as of 31 May 2013 to provide an example of comprehensive burden of disease in the 21st century from an acute animal-borne emerging infectious disease. DESIGN: We present an accurate and operable method for estimating the burden of H7N9 cases in China. The main drivers of economic loss were identified. Costs were broken down into direct (outpatient and inpatient examination and treatment) and indirect costs (cost of disability-adjusted life years (DALYs) and losses in the poultry industry), which were estimated based on field surveys and China statistical year book. SETTING: Models were applied to estimate the overall burden of H7N9 cases in China. PARTICIPANTS: 131 laboratory-confirmed H7N9 cases by 31 May 2013. OUTCOME MEASURE: Burden of H7N9 cases including direct and indirect losses. RESULTS: The total direct medical cost was ¥16 422 535 (US$2 627 606). The mean cost for each patient was ¥10 117 (US$1619) for mild patients, ¥139 323 (US$22 292) for severe cases without death and ¥205 976 (US$32 956) for severe cases with death. The total cost of DALYs was ¥17 356 561 (US$2 777 050). The poultry industry losses amounted to ¥7.75 billion (US$1.24 billion) in 10 affected provinces and ¥3.68 billion (USD$0.59 billion) in eight non-affected adjacent provinces. CONCLUSIONS: The huge poultry industry losses followed live poultry markets closing down and poultry slaughtering in some areas. Though the proportion of direct medical losses and DALYs losses in the estimate of H7N9 burden was small, the medical costs per case were extremely high (particularly for addressing the use of modern medical devices). A cost-effectiveness assessment for the intervention should be conducted in a future study.",2014 Jan 17,"['Qi, Xiaopeng', 'Jiang, Dong', 'Wang, Hongliang', 'Zhuang, Dafang', 'Ma, Jiaqi', 'Fu, Jingying', 'Qu, Jingdong', 'Sun, Yan', 'Yu, Shicheng', 'Meng, Yujie', 'Huang, Yaohuan', 'Xia, Lanfang', 'Li, Yingying', 'Wang, Yong', 'Wang, Guohua', 'Xu, Ke', 'Zhang, Qun', 'Wan, Ming', 'Su, Xuemei', 'Fu, Gang', 'Gao, George F']",BMJ Open,,,False
3b8d7417f616e8ba9912423e9b764870d8e2e047,PMC,"Systemic Spread and Propagation of a Plant-Pathogenic Virus in European Honeybees, Apis mellifera",http://dx.doi.org/10.1128/mBio.00898-13,PMC3903276,24449751,CC BY-NC-SA,"Emerging and reemerging diseases that result from pathogen host shifts are a threat to the health of humans and their domesticates. RNA viruses have extremely high mutation rates and thus represent a significant source of these infectious diseases. In the present study, we showed that a plant-pathogenic RNA virus, tobacco ringspot virus (TRSV), could replicate and produce virions in honeybees, Apis mellifera, resulting in infections that were found throughout the entire body. Additionally, we showed that TRSV-infected individuals were continually present in some monitored colonies. While intracellular life cycle, species-level genetic variation, and pathogenesis of the virus in honeybee hosts remain to be determined, the increasing prevalence of TRSV in conjunction with other bee viruses from spring toward winter in infected colonies was associated with gradual decline of host populations and winter colony collapse, suggesting the negative impact of the virus on colony survival. Furthermore, we showed that TRSV was also found in ectoparasitic Varroa mites that feed on bee hemolymph, but in those instances the virus was restricted to the gastric cecum of Varroa mites, suggesting that Varroa mites may facilitate the spread of TRSV in bees but do not experience systemic invasion. Finally, our phylogenetic analysis revealed that TRSV isolates from bees, bee pollen, and Varroa mites clustered together, forming a monophyletic clade. The tree topology indicated that the TRSVs from arthropod hosts shared a common ancestor with those from plant hosts and subsequently evolved as a distinct lineage after transkingdom host alteration. This study represents a unique example of viruses with host ranges spanning both the plant and animal kingdoms.",2014 Jan 21,"['Li, Ji Lian', 'Cornman, R. Scott', 'Evans, Jay D.', 'Pettis, Jeffery S.', 'Zhao, Yan', 'Murphy, Charles', 'Peng, Wen Jun', 'Wu, Jie', 'Hamilton, Michele', 'Boncristiani, Humberto F.', 'Zhou, Liang', 'Hammond, John', 'Chen, Yan Ping']",mBio,,,True
dfe23d64895beefb7e0fec49126c49d982ffe8da,PMC,Making vaccines “on demand”: A potential solution for emerging pathogens and biodefense?,http://dx.doi.org/10.4161/hv.25611,PMC3906351,23877094,CC BY-NC,"The integrated US Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) has made great strides in strategic preparedness and response capabilities. There have been numerous advances in planning, biothreat countermeasure development, licensure, manufacturing, stockpiling and deployment. Increased biodefense surveillance capability has dramatically improved, while new tools and increased awareness have fostered rapid identification of new potential public health pathogens. Unfortunately, structural delays in vaccine design, development, manufacture, clinical testing and licensure processes remain significant obstacles to an effective national biodefense rapid response capability. This is particularly true for the very real threat of “novel pathogens” such as the avian-origin influenzas H7N9 and H5N1, and new coronaviruses such as hCoV-EMC. Conventional approaches to vaccine development, production, clinical testing and licensure are incompatible with the prompt deployment needed for an effective public health response. An alternative approach, proposed here, is to apply computational vaccine design tools and rapid production technologies that now make it possible to engineer vaccines for novel emerging pathogen and WMD biowarfare agent countermeasures in record time. These new tools have the potential to significantly reduce the time needed to design string-of-epitope vaccines for previously unknown pathogens. The design process—from genome to gene sequence, ready to insert in a DNA plasmid—can now be accomplished in less than 24 h. While these vaccines are by no means “standard,” the need for innovation in the vaccine design and production process is great. Should such vaccines be developed, their 60-d start-to-finish timeline would represent a 2-fold faster response than the current standard.",2013 Sep 1,"['De Groot, Anne S', 'Einck, Leo', 'Moise, Leonard', 'Chambers, Michael', 'Ballantyne, John', 'Malone, Robert W', 'Ardito, Matthew', 'Martin, William']",Hum Vaccin Immunother,,,True
0b064096b51c4cada7b64af37eae826b7e7c9649,PMC,Role of CD25(+) CD4(+) T cells in acute and persistent coronavirus infection of the central nervous system,http://dx.doi.org/10.1016/j.virol.2013.08.030,PMC3906923,24210105,CC BY-NC-SA,"The influence of CD25(+)CD4(+) regulatory T cells (Treg) on acute and chronic viral infection of the central nervous system (CNS) was examined using a glial tropic murine coronavirus. Treg in the CNS were highest during initial T cell mediated virus control, decreased and then remained relatively stable during persistence. Anti-CD25 treatment did not affect CNS recruitment of inflammatory cells. Viral control was initially delayed; however, neither the kinetics of viral control nor viral persistence were affected. By contrast, the absence of Treg during the acute phase resulted in increased demyelination during viral persistence. These data suggest that CNS inflammation, progression of viral control and viral persistence are relatively independent of CD25(+)CD4(+) Treg. However, their absence during acute infection alters the ability of the host to limit tissue damage.",2013 Dec 24,"['de Aquino, Maria Teresa P.', 'Puntambekar, Shweta S.', 'Savarin, Carine', 'Bergmann, Cornelia C.', 'Phares, Timothy W.', 'Hinton, David R.', 'Stohlman, Stephen A.']",Virology,,,True
6bc66c3abc451b39ae1bba08b1f1ff3f7e7f5b95,PMC,Adjuvanted poly(lactic-co-glycolic) acid nanoparticle-entrapped inactivated porcine reproductive and respiratory syndrome virus vaccine elicits cross-protective immune response in pigs,http://dx.doi.org/10.2147/IJN.S56127,PMC3908835,24493925,CC BY-NC,"Porcine reproductive and respiratory syndrome (PRRS), caused by the PRRS virus (PRRSV), is an economically devastating disease, causing daily losses of approximately $3 million to the US pork industry. Current vaccines have failed to completely prevent PRRS outbreaks. Recently, we have shown that poly(lactic-co-glycolic) acid (PLGA) nanoparticle-entrapped inactivated PRRSV vaccine (NP-KAg) induces a cross-protective immune response in pigs. To further improve its cross-protective efficacy, the NP-KAg vaccine formulation was slightly modified, and pigs were coadministered the vaccine twice intranasally with a potent adjuvant: Mycobacterium tuberculosis whole-cell lysate. In vaccinated virulent heterologous PRRSV-challenged pigs, the immune correlates in the blood were as follows: 1) enhanced PRRSV-specific antibody response with enhanced avidity of both immunoglobulin (Ig)-G and IgA isotypes, associated with augmented virus-neutralizing antibody titers; 2) comparable and increased levels of virus-specific IgG(1) and IgG(2) antibody subtypes and production of high levels of both T-helper (Th)-1 and Th2 cytokines, indicative of a balanced Th1–Th2 response; 3) suppressed immunosuppressive cytokine response; 4) increased frequency of interferon-γ(+) lymphocyte subsets and expanded population of antigen-presenting cells; and most importantly 5) complete clearance of detectable replicating challenged heterologous PRRSV and close to threefold reduction in viral ribonucleic acid load detected in the blood. In conclusion, intranasal delivery of adjuvanted NP-KAg vaccine formulation to growing pigs elicited a broadly cross-protective immune response, showing the potential of this innovative vaccination strategy to prevent PRRS outbreaks in pigs. A similar approach to control other respiratory diseases in food animals and humans appears to be feasible.",2014 Jan 24,"['Binjawadagi, Basavaraj', 'Dwivedi, Varun', 'Manickam, Cordelia', 'Ouyang, Kang', 'Wu, Yun', 'Lee, Ly James', 'Torrelles, Jordi B', 'Renukaradhya, Gourapura J']",Int J Nanomedicine,,,True
d74ca96879ef6d9982cb7ddaf5396940697dc8dc,PMC,Imino sugar glucosidase inhibitors as broadly active anti-filovirus agents,http://dx.doi.org/10.1038/emi.2013.77,PMC3924557,26038444,CC BY-NC-SA,"Ebola virus and Marburg virus are members of the family of Filoviridae and are etiological agents of a deadly hemorrhagic fever disease. The clinical symptoms of Ebola and Marburg hemorrhagic fevers are difficult to distinguish and there are currently no specific antiviral therapies against either of the viruses. Therefore, a drug that is safe and effective against both would be an enormous breakthrough. We and others have shown that the folding of the glycoproteins of many enveloped viruses, including the filoviruses, is far more dependent upon the calnexin pathway of protein folding than are most host glycoproteins. Drugs that inhibit this pathway would be expected to be selectively antiviral. Indeed, as we summarize in this review, imino sugars that are competitive inhibitors of the host endoplasmic reticular α-glucosidases I and II, which are enzymes that process N-glycan on nascent glycoproteins and thereby inhibit calnexin binding to the nascent glycoproteins, have been shown to have antiviral activity against a number of enveloped viruses including filoviruses. In this review, we describe the state of development of imino sugars for use against the filoviruses, and provide an explanation for the basis of their antiviral activity as well as limitations.",2013 Nov 20,"['Chang, Jinhong', 'Guo, Ju-Tao', 'Du, Yanming', 'Block, Timothy']",Emerg Microbes Infect,,,True
4c819d4002a693bae0a39b5d0a282c4feac3f184,PMC,Can biowarfare agents be defeated with light?,http://dx.doi.org/10.4161/viru.26475,PMC3925713,24067444,CC BY-NC,"Biological warfare and bioterrorism is an unpleasant fact of 21st century life. Highly infectious and profoundly virulent diseases may be caused in combat personnel or in civilian populations by the appropriate dissemination of viruses, bacteria, spores, fungi, or toxins. Dissemination may be airborne, waterborne, or by contamination of food or surfaces. Countermeasures may be directed toward destroying or neutralizing the agents outside the body before infection has taken place, by destroying the agents once they have entered the body before the disease has fully developed, or by immunizing susceptible populations against the effects. A range of light-based technologies may have a role to play in biodefense countermeasures. Germicidal UV (UVC) is exceptionally active in destroying a wide range of viruses and microbial cells, and recent data suggests that UVC has high selectivity over host mammalian cells and tissues. Two UVA mediated approaches may also have roles to play; one where UVA is combined with titanium dioxide nanoparticles in a process called photocatalysis, and a second where UVA is combined with psoralens (PUVA) to produce “killed but metabolically active” microbial cells that may be particularly suitable for vaccines. Many microbial cells are surprisingly sensitive to blue light alone, and blue light can effectively destroy bacteria, fungi, and Bacillus spores and can treat wound infections. The combination of photosensitizing dyes such as porphyrins or phenothiaziniums and red light is called photodynamic therapy (PDT) or photoinactivation, and this approach cannot only kill bacteria, spores, and fungi, but also inactivate viruses and toxins. Many reports have highlighted the ability of PDT to treat infections and stimulate the host immune system. Finally pulsed (femtosecond) high power lasers have been used to inactivate pathogens with some degree of selectivity. We have pointed to some of the ways light-based technology may be used to defeat biological warfare in the future.",2013 Nov 15,"['Vatansever, Fatma', 'Ferraresi, Cleber', 'de Sousa, Marcelo Victor Pires', 'Yin, Rui', 'Rineh, Ardeshir', 'Sharma, Sulbha K', 'Hamblin, Michael R']",Virulence,,,True
4a17794fa919d411ae351c9d671d4d1a6d64cc99,PMC,Generation of “LYmph Node Derived Antibody Libraries” (LYNDAL) for selecting fully human antibody fragments with therapeutic potential,http://dx.doi.org/10.4161/mabs.27236,PMC3929437,24256717,CC BY-NC,"The development of efficient strategies for generating fully human monoclonal antibodies with unique functional properties that are exploitable for tailored therapeutic interventions remains a major challenge in the antibody technology field. Here, we present a methodology for recovering such antibodies from antigen-encountered human B cell repertoires. As the source for variable antibody genes, we cloned immunoglobulin G (IgG)-derived B cell repertoires from lymph nodes of 20 individuals undergoing surgery for head and neck cancer. Sequence analysis of unselected “LYmph Node Derived Antibody Libraries” (LYNDAL) revealed a naturally occurring distribution pattern of rearranged antibody sequences, representing all known variable gene families and most functional germline sequences. To demonstrate the feasibility for selecting antibodies with therapeutic potential from these repertoires, seven LYNDAL from donors with high serum titers against herpes simplex virus (HSV) were panned on recombinant glycoprotein B of HSV-1. Screening for specific binders delivered 34 single-chain variable fragments (scFvs) with unique sequences. Sequence analysis revealed extensive somatic hypermutation of enriched clones as a result of affinity maturation. Binding of scFvs to common glycoprotein B variants from HSV-1 and HSV-2 strains was highly specific, and the majority of analyzed antibody fragments bound to the target antigen with nanomolar affinity. From eight scFvs with HSV-neutralizing capacity in vitro, the most potent antibody neutralized 50% HSV-2 at 4.5 nM as a dimeric (scFv)(2). We anticipate our approach to be useful for recovering fully human antibodies with therapeutic potential.",2014 Jan 1,"['Diebolder, Philipp', 'Keller, Armin', 'Haase, Stephanie', 'Schlegelmilch, Anne', 'Kiefer, Jonathan D', 'Karimi, Tamana', 'Weber, Tobias', 'Moldenhauer, Gerhard', 'Kehm, Roland', 'Eis-Hübinger, Anna M', 'Jäger, Dirk', 'Federspil, Philippe A', 'Herold-Mende, Christel', 'Dyckhoff, Gerhard', 'Kontermann, Roland E', 'Arndt, Michaela AE', 'Krauss, Jürgen']",MAbs,,,True
af9e845d14fdb65bcb14b59b0f3ddc76a9517c5a,PMC,"Outbreak of febrile respiratory illness associated with human adenovirus type 14p1 in Gansu Province, China",http://dx.doi.org/10.1111/irv.12118,PMC3933759,23692915,CC BY-NC-ND,"OBJECTIVES: Human adenovirus (HAdV) type 14 had been infrequently associated with outbreaks of febrile respiratory illness (FRI) until the HAdV‐14p1 emerged in 2006 and rapidly spread in the United States. Here, we report an outbreak of FRI caused by HadV‐14p1 that occurred in 2011 at a primary and middle school in China. DESIGN: The basic information of the outbreak was recored; throat swabs were collected from 17 patients, polymerase chain reaction, A549 cell culture, and sequencing were used to identify the pathogen of the outbreak.. RESULTS: Total of 43 students were infected in this outbreak. Boys were more than girls. We identified 11 HAdV‐positive specimens and 6 HAdV isolates. Genetic analysis showed that the complete hexon, fiber, and E1A sequences of isolates were nearly 100% identical with other HAdV‐14p1 sequences deposited in GenBank. CONCLUSIONS: HadV‐14p1 has caused outbreaks of pneumonia and mortality among adults in the United States and Europe. It may cause similar conditions among Chinese adults due to poor hygiene and sanitation. It seems prudent for China to develop a national surveillance system to determine the etiology of severe respiratory diseases and deaths among adults and school‐aged children.",2013 Nov 22,"['Huang, Guohong', 'Yu, Deshan', 'Zhu, Zhen', 'Zhao, Hai', 'Wang, Peng', 'Gray, Gregory C.', 'Meng, Lei', 'Xu, Wenbo']",Influenza Other Respir Viruses,,,True
62cd5be77a70a55d18199836987e521d4b992cbd,PMC,Building and Optimizing a Virus-specific T Cell Receptor Library for Targeted Immunotherapy in Viral Infections,http://dx.doi.org/10.1038/srep04166,PMC3933865,24566718,CC BY-NC-SA,"Restoration of antigen-specific T cell immunity has the potential to clear persistent viral infection. T cell receptor (TCR) gene therapy can reconstitute CD8 T cell immunity in chronic patients. We cloned 10 virus-specific TCRs targeting 5 different viruses, causing chronic and acute infection. All 10 TCR genetic constructs were optimized for expression using a P2A sequence, codon optimization and the addition of a non-native disulfide bond. However, maximum TCR expression was only achieved after establishing the optimal orientation of the alpha and beta chains in the expression cassette; 9/10 TCRs favored the beta-P2A-alpha orientation over alpha-P2A-beta. Optimal TCR expression was associated with a significant increase in the frequency of IFN-gamma+ T cells. In addition, activating cells for transduction in the presence of Toll-like receptor ligands further enhanced IFN-gamma production. Thus, we have built a virus-specific TCR library that has potential for therapeutic intervention in chronic viral infection or virus-related cancers.",2014 Feb 25,"['Banu, Nasirah', 'Chia, Adeline', 'Ho, Zi Zong', 'Garcia, Alfonso Tan', 'Paravasivam, Komathi', 'Grotenbreg, Gijsbert M.', 'Bertoletti, Antonio', 'Gehring, Adam J.']",Sci Rep,,,True
61b8415c8659a58c24af2b8a2456bed96b61b609,PMC,Advancing a multivalent ‘Pan-anthelmintic’ vaccine against soil-transmitted nematode infections,http://dx.doi.org/10.1586/14760584.2014.872035,PMC3934375,24392641,CC BY-NC,"ASCARIS LUMBRICOIDES: The Sabin Vaccine Institute Product Development Partnership is developing a Pan-anthelmintic vaccine that simultaneously targets the major soil-transmitted nematode infections, in other words, ascariasis, trichuriasis and hookworm infection. The approach builds off the current bivalent Human Hookworm Vaccine now in clinical development and would ultimately add both a larval Ascaris lumbricoides antigen and an adult-stage Trichuris trichiura antigen from the parasite stichosome. Each selected antigen would partially reproduce the protective immunity afforded by UV-attenuated Ascaris eggs and Trichuris stichosome extracts, respectively. Final antigen selection will apply a ranking system that includes the evaluation of expression yields and solubility, feasibility of process development and the absence of circulating antigen-specific IgE among populations living in helminth-endemic regions. Here we describe a five year roadmap for the antigen discovery, feasibility and antigen selection, which will ultimately lead to the scale-up expression, process development, manufacture, good laboratory practices toxicology and preclinical evaluation, ultimately leading to Phase 1 clinical testing.",2014 Mar 6,"['Zhan, Bin', 'Beaumier, Coreen M', 'Briggs, Neima', 'Jones, Kathryn M', 'Keegan, Brian P', 'Bottazzi, Maria Elena', 'Hotez, Peter J']",Expert Rev Vaccines,,,True
37afb28ad52f876fd3473878e7990165663f3bd2,PMC,Association between respiratory viruses and asthma exacerbations,http://dx.doi.org/10.3345/kjp.2014.57.1.26,PMC3935109,24578713,CC BY-NC,,2014 Jan 31,"Kim, Woo Kyung",Korean J Pediatr,,,True
6c6b13bdca7f70d6afec7257e4769bb5c10b1a19,PMC,Cell-Type-Specific Effects of RNase L on Viral Induction of Beta Interferon,http://dx.doi.org/10.1128/mBio.00856-14,PMC3940032,24570368,CC BY-NC-SA,"The interferon (IFN)-inducible antiviral state is mediated in part by the 2′,5′-oligoadenylate (2-5A) synthetase (OAS)/RNase L system. 2-5A, produced from ATP by OAS proteins in response to viral double-stranded RNA, binds to and activates RNase L. RNase L restricts viral infections by degrading viral and cellular RNA, inducing autophagy and apoptosis, and producing RNA degradation products that amplify production of type I interferons (IFNs) through RIG-I-like receptors. However, the effects of the OAS/RNase L pathway on IFN induction in different cell types that vary in basal levels of these proteins have not been previously reported. Here we report higher basal expression of both RNase L and OAS in mouse macrophages in comparison to mouse embryonic fibroblasts (MEFs). In MEFs, RNase L gene knockout decreased induction of IFN-β by encephalomyocarditis virus infection or poly(rI):poly(rC) (pIC) transfection. In contrast, in macrophages, RNase L deletion increased (rather than decreased) induction of IFN-β by virus or pIC. RNA damage from RNase L in virus-infected macrophages is likely responsible for reducing IFN-β production. Similarly, direct activation of RNase L by transfection with 2-5A induced IFN-β in MEFs but not in macrophages. Also, viral infection or pIC transfection caused RNase L-dependent apoptosis of macrophages but not of MEFs. Our results suggest that cell-type-specific differences in basal levels of OAS and RNase L are determinants of IFN-β induction that could affect tissue protection and survival during viral infections.",2014 Feb 25,"['Banerjee, Shuvojit', 'Chakrabarti, Arindam', 'Jha, Babal Kant', 'Weiss, Susan R.', 'Silverman, Robert H.']",mBio,,,True
6909d7db535645308e0b2e726b5dea3b854a1aa5,PMC,Middle East Respiratory Syndrome Coronavirus Infection in Dromedary Camels in Saudi Arabia,http://dx.doi.org/10.1128/mBio.00884-14,PMC3940034,24570370,CC BY-NC-SA,"The Middle East respiratory syndrome (MERS) is proposed to be a zoonotic disease; however, the reservoir and mechanism for transmission of the causative agent, the MERS coronavirus, are unknown. Dromedary camels have been implicated through reports that some victims have been exposed to camels, camels in areas where the disease has emerged have antibodies to the virus, and viral sequences have been recovered from camels in association with outbreaks of the disease among humans. Nonetheless, whether camels mediate transmission to humans is unresolved. Here we provide evidence from a geographic and temporal survey of camels in the Kingdom of Saudi Arabia that MERS coronaviruses have been circulating in camels since at least 1992, are distributed countrywide, and can be phylogenetically classified into clades that correlate with outbreaks of the disease among humans. We found no evidence of infection in domestic sheep or domestic goats.",2014 Feb 25,"['Alagaili, Abdulaziz N.', 'Briese, Thomas', 'Mishra, Nischay', 'Kapoor, Vishal', 'Sameroff, Stephen C.', 'de Wit, Emmie', 'Munster, Vincent J.', 'Hensley, Lisa E.', 'Zalmout, Iyad S.', 'Kapoor, Amit', 'Epstein, Jonathan H.', 'Karesh, William B.', 'Daszak, Peter', 'Mohammed, Osama B.', 'Lipkin, W. Ian']",mBio,,,True
efd6ea1e3d5223f220c6c09084ac5fb043618b03,PMC,Adeno-Associated Viruses Serotype 2-Mediated RNA Interference Efficiently Inhibits Rabies Virus Replication In Vitro and In Vivo,http://dx.doi.org/10.1292/jvms.13-0127,PMC3942934,23774028,CC BY-NC-ND,"To investigate the potential of adeno-associated viruses serotype 2 (AAV2)-mediated RNA interference (RNAi) as an antiviral agent against rabies, recombinant AAV2 vectors expressing siRNA targeting the nucleoprotein (N) gene of rabies virus (RABV) (rAAV-N796) were constructed and evaluated. When NA cells pretreated with rAAV-N796 were challenged with RABV, there was a 37.8 ± 3.4% to 55.1 ± 5.3% reduction in RABV virus titer. When cells pre-challenged with RABV were treated with rAAV-N796, there was a 4.4 ± 1.4 to 28.8 ± 3.2% reduction in RABV virus titer. Relative quantification of RABV transcripts using real-time PCR and Western blot revealed that the knockdown of RABV-N gene transcripts was based on the rAAV-N796 inoculation titer. When any NA cells were treated with rAAV-N796 before or after challenged with RABV, significant reduction in virus titer was observed in both administrations. Mice treated intracerebrally with rAAV-N796 exhibited 50 ± 5.3 and 62.5 ± 4.7% protection when challenged intracerebrally or intramuscally, respectively, with lethal RABV. When mice treated intramuscularly with rAAV-N796 were challenged intramuscularly with lethal RABV, they exhibited 37.5 ± 3.7% protection. When mice were intracerebrally and intramuscularly with rAAV-N796 24 hr after exposure to RABV infection, they exhibited 25 ± 4.1% protection The N gene mRNA levels in the brains of challenged mice with three different administrations were reduced (55, 68, 32 and 25%, respectively). These results indicated that AAV2 vector-mediated siRNA delivery in vitro in NA cells inhibited RABV multiplication, inhibited RABV multiplication in vivo in the mice brain and imparted partial protection against lethal rabies. So, it may have a potential to be used as an alternative antiviral approach against rabies.",2013 Oct 14,"['WU, Hong-Xia', 'WANG, Hua-Lei', 'GUO, Xiao-Feng', 'YANG, Yu-Jiao', 'MA, Jin-Zhu', 'WANG, Tie-Cheng', 'GAO, Yu-Wei', 'ZHAO, Yong-Kun', 'YANG, Song-Tao', 'XIA, Xian-Zhu']",J Vet Med Sci,,,True
5cba1e45c2829cb0ebaa7bf5384fa685f543c6d6,PMC,Detection of Ascitic Feline Coronavirus RNA from Cats with Clinically Suspected Feline Infectious Peritonitis,http://dx.doi.org/10.1292/jvms.13-0094,PMC3942943,23719724,CC BY-NC-ND,"Ascitic feline coronavirus (FCoV) RNA was examined in 854 cats with suspected feline infectious peritonitis (FIP) by RT-PCR. The positivity was significantly higher in purebreds (62.2%) than in crossbreds (34.8%) (P<0.0001). Among purebreds, the positivities in the Norwegian forest cat (92.3%) and Scottish fold (77.6%) were significantly higher than the average of purebreds (P=0.0274 and 0.0251, respectively). The positivity was significantly higher in males (51.5%) than in females (35.7%) (P<0.0001), whereas no gender difference has generally been noted in FCoV antibody prevalence, indicating that FIP more frequently develops in males among FCoV-infected cats. Genotyping was performed for 377 gene-positive specimens. Type I (83.3%) was far more predominantly detected than type II (10.6%) (P<0.0001), similar to previous serological and genetic surveys.",2013 Oct 29,"['SOMA, Takehisa', 'WADA, Makoto', 'TAHARAGUCHI, Satoshi', 'TAJIMA, Tomoko']",J Vet Med Sci,,,True
71b5ffbc04fa339eed42ead8bb5dd1bf0e471b8f,PMC,"Detection of Bovine Group A Rotavirus Using Rapid Antigen Detection Kits, RT-PCR and Next-Generation DNA Sequencing",http://dx.doi.org/10.1292/jvms.13-0265,PMC3942952,23912876,CC BY-NC-ND,"We investigated the sensitivity of human rotavirus rapid antigen detection (RAD) kits, RT-PCR and next-generation DNA sequencing (NGS) for detection of bovine group A rotavirus (RVA). The Dipstick ‘Eiken’ Rota (Dipstick) showed the highest sensitivity out of the seven RAD kits against all selected strains in limited dilution analyses, which was consistent with the results for equine rotavirus previously reported. RT-PCR had 10(0)–10(3)-fold higher sensitivity than the Dipstick. NGS using thirteen RT-PCR-negative fecal samples revealed that all samples yielded RVA reads and especially that two of them covered all 11 genome segments. Moreover, mapping reads to reference sequences allowed genotyping. The NGS would be sensitive and useful for analysis of less dependent on specific primers and screening of genotypes.",2013 Dec 2,"['MINAMI-FUKUDA, Fujiko', 'NAGAI, Makoto', 'TAKAI, Hikaru', 'MURAKAMI, Toshiaki', 'OZAWA, Tadashi', 'TSUCHIAKA, Shinobu', 'OKAZAKI, Sachiko', 'KATAYAMA, Yukie', 'OBA, Mami', 'NISHIURA, Naomi', 'SASSA, Yukiko', 'OMATSU, Tsutomu', 'FURUYA, Tetsuya', 'KOYAMA, Satoshi', 'SHIRAI, Junsuke', 'TSUNEMITSU, Hiroshi', 'FUJII, Yoshiki', 'KATAYAMA, Kazuhiko', 'MIZUTANI, Tetsuya']",J Vet Med Sci,,,True
b432613a1d3f049f7c75942e8dca5e3af1de7b69,PMC,"Spread, Circulation, and Evolution of the Middle East Respiratory Syndrome Coronavirus",http://dx.doi.org/10.1128/mBio.01062-13,PMC3944817,24549846,CC BY-NC-SA,"The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 × 10(−3) substitutions per site per year (95% credible interval [95% CI], 8.76 × 10(−4); 1.37 × 10(−3)) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R(0)) for the virus that is less than 1.",2014 Feb 18,"['Cotten, Matthew', 'Watson, Simon J.', 'Zumla, Alimuddin I.', 'Makhdoom, Hatem Q.', 'Palser, Anne L.', 'Ong, Swee Hoe', 'Al Rabeeah, Abdullah A.', 'Alhakeem, Rafat F.', 'Assiri, Abdullah', 'Al-Tawfiq, Jaffar A.', 'Albarrak, Ali', 'Barry, Mazin', 'Shibl, Atef', 'Alrabiah, Fahad A.', 'Hajjar, Sami', 'Balkhy, Hanan H.', 'Flemban, Hesham', 'Rambaut, Andrew', 'Kellam, Paul', 'Memish, Ziad A.']",mBio,,,True
09da5dea6fa9b08b2eb1549e85cbc7e29fd3f2f8,PMC,Very small embryonic-like stem cells (VSELs) represent a real challenge in stem cell biology: recent pros and cons in the midst of a lively debate,http://dx.doi.org/10.1038/leu.2013.255,PMC3948156,24018851,CC BY-NC-ND,"The concept that adult tissue, including bone marrow (BM), contains early-development cells with broader differentiation potential has again been recently challenged. In response, we would like to review the accumulated evidence from several independent laboratories that adult tissues, including BM, harbor a population of very rare stem cells that may cross germ layers in their differentiation potential. Thus, the BM stem cell compartment hierarchy needs to be revisited. These dormant, early-development cells that our group described as very small embryonic-like stem cells (VSELs) most likely overlap with similar populations of stem cells that have been identified in adult tissues by other investigators as the result of various experimental strategies and have been given various names. As reported, murine VSELs have some pluripotent stem cell characteristics. Moreover, they display several epiblast/germline markers that suggest their embryonic origin and developmental deposition in adult BM. Moreover, at the molecular level, changes in expression of parentally imprinted genes (for example, Igf2–H19) and resistance to insulin/insulin-like growth factor signaling (IIS) regulates their quiescent state in adult tissues. In several emergency situations related to organ damage, VSELs can be activated and mobilized into peripheral blood, and in appropriate animal models they contribute to tissue organ/regeneration. Interestingly, their number correlates with lifespan in mice, and they may also be involved in some malignancies. VSELs have been successfully isolated in several laboratories; however, some investigators experience problems with their isolation.",2014 Mar 4,"['Ratajczak, M Z', 'Zuba-Surma, E', 'Wojakowski, W', 'Suszynska, M', 'Mierzejewska, K', 'Liu, R', 'Ratajczak, J', 'Shin, D M', 'Kucia, M']",Leukemia,,,True
a802010092ba72fa679f88467ea9b53ac6725577,PMC,What makes the hospitalisation system more efficient? An application of the decomposition method to Hong Kong morbidity data,http://dx.doi.org/10.1136/bmjopen-2013-003903,PMC3948574,24604479,CC BY-NC,"OBJECTIVE: To examine the efficiency of the Hong Kong hospitalisation system based on hospitalisation days. DESIGN: Retrospective study. SETTING: Hospitalisation data (2000–2010) for all government-funded hospitals in Hong Kong. POPULATION: Hospitalisation data for the entire Hong Kong population (7.0 million in 2011). METHODS: A decomposition method was used to determine the effects on total hospitalisation days during the period 2000–2010 of the following three factors: (i) hospitalisation rate per person; (ii) the number of visits per patient; and (iii) the mean duration of stay per visit. MAIN OUTCOME MEASURES: The decomposition method provides empirical measures of how the three factors contributed to the change in total hospitalisation days during the period 2000–2010 and identifies the most effective way to contain increases in hospitalisation days. RESULTS: The results of decomposition analysis show that the decrease in mean duration of stay per visit (reducing from 6.83 to 4.58 days) is the most important factor in the reduction in the total number of hospitalisation days, despite increases in total population size (from 6.7 to 7.0 million), the number of individual hospital admissions (from 583 000 to 664 000) and the number of episodes (from 1.2 to 1.4 million) from 2000 to 2010. Hospitalisation days per person decreased from 1.18 in 2000 to 0.93 in 2010. The decline in the mean duration of stay per visit contributed 200.6% to this reduction but was offset by −51.1% due to a slight growth in the number of visits per patient and by −49.4% as a result of changed hospitalisation rates per person. CONCLUSIONS: Better management of the duration of stay of per visit without compromising patient satisfaction levels or the quality of service is the most important factor for controlling increases in health expenditure in Hong Kong.",2014 Mar 6,"['Yip, Paul S F', 'Lee, Carmen K M', 'Chow, Chun-Bong', 'Lo, William T L']",BMJ Open,,,True
eea1eb720701f6b9dbb08915e800964d963a933e,PMC,What makes the hospitalisation system more efficient? An application of the decomposition method to Hong Kong morbidity data,http://dx.doi.org/10.1136/bmjopen-2013-003903,PMC3948574,24604479,CC BY-NC,"OBJECTIVE: To examine the efficiency of the Hong Kong hospitalisation system based on hospitalisation days. DESIGN: Retrospective study. SETTING: Hospitalisation data (2000–2010) for all government-funded hospitals in Hong Kong. POPULATION: Hospitalisation data for the entire Hong Kong population (7.0 million in 2011). METHODS: A decomposition method was used to determine the effects on total hospitalisation days during the period 2000–2010 of the following three factors: (i) hospitalisation rate per person; (ii) the number of visits per patient; and (iii) the mean duration of stay per visit. MAIN OUTCOME MEASURES: The decomposition method provides empirical measures of how the three factors contributed to the change in total hospitalisation days during the period 2000–2010 and identifies the most effective way to contain increases in hospitalisation days. RESULTS: The results of decomposition analysis show that the decrease in mean duration of stay per visit (reducing from 6.83 to 4.58 days) is the most important factor in the reduction in the total number of hospitalisation days, despite increases in total population size (from 6.7 to 7.0 million), the number of individual hospital admissions (from 583 000 to 664 000) and the number of episodes (from 1.2 to 1.4 million) from 2000 to 2010. Hospitalisation days per person decreased from 1.18 in 2000 to 0.93 in 2010. The decline in the mean duration of stay per visit contributed 200.6% to this reduction but was offset by −51.1% due to a slight growth in the number of visits per patient and by −49.4% as a result of changed hospitalisation rates per person. CONCLUSIONS: Better management of the duration of stay of per visit without compromising patient satisfaction levels or the quality of service is the most important factor for controlling increases in health expenditure in Hong Kong.",2014 Mar 6,"['Yip, Paul S F', 'Lee, Carmen K M', 'Chow, Chun-Bong', 'Lo, William T L']",BMJ Open,,,True
6650ffd1d34f97777bc8be332e7788159ccc4574,PMC,What makes the hospitalisation system more efficient? An application of the decomposition method to Hong Kong morbidity data,http://dx.doi.org/10.1136/bmjopen-2013-003903,PMC3948574,24604479,CC BY-NC,"OBJECTIVE: To examine the efficiency of the Hong Kong hospitalisation system based on hospitalisation days. DESIGN: Retrospective study. SETTING: Hospitalisation data (2000–2010) for all government-funded hospitals in Hong Kong. POPULATION: Hospitalisation data for the entire Hong Kong population (7.0 million in 2011). METHODS: A decomposition method was used to determine the effects on total hospitalisation days during the period 2000–2010 of the following three factors: (i) hospitalisation rate per person; (ii) the number of visits per patient; and (iii) the mean duration of stay per visit. MAIN OUTCOME MEASURES: The decomposition method provides empirical measures of how the three factors contributed to the change in total hospitalisation days during the period 2000–2010 and identifies the most effective way to contain increases in hospitalisation days. RESULTS: The results of decomposition analysis show that the decrease in mean duration of stay per visit (reducing from 6.83 to 4.58 days) is the most important factor in the reduction in the total number of hospitalisation days, despite increases in total population size (from 6.7 to 7.0 million), the number of individual hospital admissions (from 583 000 to 664 000) and the number of episodes (from 1.2 to 1.4 million) from 2000 to 2010. Hospitalisation days per person decreased from 1.18 in 2000 to 0.93 in 2010. The decline in the mean duration of stay per visit contributed 200.6% to this reduction but was offset by −51.1% due to a slight growth in the number of visits per patient and by −49.4% as a result of changed hospitalisation rates per person. CONCLUSIONS: Better management of the duration of stay of per visit without compromising patient satisfaction levels or the quality of service is the most important factor for controlling increases in health expenditure in Hong Kong.",2014 Mar 6,"['Yip, Paul S F', 'Lee, Carmen K M', 'Chow, Chun-Bong', 'Lo, William T L']",BMJ Open,,,False
2a23841a09149d099f936ecc2edf913b9d2dc2ce,PMC,"Acute Exacerbation and Respiratory InfectionS in COPD (AERIS): protocol for a prospective, observational cohort study",http://dx.doi.org/10.1136/bmjopen-2013-004546,PMC3948575,24607562,CC BY-NC,"INTRODUCTION: The aetiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) remains incompletely understood and strategies for treatment and prevention have not altered significantly for many years. Improved understanding of the role of respiratory pathogens in acute exacerbations of COPD (AECOPD) is required and the use of molecular microbiological techniques may lead to insights into host–pathogen interactions and the development of more targeted therapeutic approaches. METHODS AND ANALYSES: Acute Exacerbation and Respiratory InfectionS in COPD (AERIS) is a longitudinal epidemiological study to assess how changes in the COPD airway microbiome contribute to the incidence and severity of AECOPD. Patients with COPD aged 40–85 are followed monthly for 2 years, and reviewed within 72 h of onset of symptoms of AECOPD. Exacerbations are detected using daily electronic diary cards. Blood, sputum, nasopharyngeal and urine samples are collected at prespecified timepoints. Molecular diagnostic and typing techniques are used to describe the dynamics of airway infection during AECOPD and stable disease, and associations with clinical outcome. This study aims to refine the case definition of AECOPD to reflect the possible microbiological aetiology. AERIS will assess the impact of AECOPD on health-related quality of life and healthcare resource utilisation, and the possible interactions between nutritional status, infection and immune responses. ETHICS AND DISSEMINATION: AERIS is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice, and has been approved by the institutional ethics and review board. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications. DISCUSSION: Few other studies have addressed the complexity of the microbiological and systemic components of COPD or employed real-time electronic tracking of symptoms to identify AECOPD and potential aetiological triggers. RESULTS: Results of AERIS will increase our understanding of the contribution of pathogens to AECOPD, potentially leading to new targeted therapeutic and preventative interventions. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01360398.",2014 Mar 7,"['Bourne, Simon', 'Cohet, Catherine', 'Kim, Viktoriya', 'Barton, Anna', 'Tuck, Andy', 'Aris, Emmanuel', 'Mesia-Vela, Sonia', 'Devaster, Jeanne-Marie', 'Ballou, W Ripley', 'Clarke, Stuart', 'Wilkinson, Tom']",BMJ Open,,,True
fbb2b307ad6be9561286c3b8a9114d283fb2e224,PMC,"Acute Exacerbation and Respiratory InfectionS in COPD (AERIS): protocol for a prospective, observational cohort study",http://dx.doi.org/10.1136/bmjopen-2013-004546,PMC3948575,24607562,CC BY-NC,"INTRODUCTION: The aetiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) remains incompletely understood and strategies for treatment and prevention have not altered significantly for many years. Improved understanding of the role of respiratory pathogens in acute exacerbations of COPD (AECOPD) is required and the use of molecular microbiological techniques may lead to insights into host–pathogen interactions and the development of more targeted therapeutic approaches. METHODS AND ANALYSES: Acute Exacerbation and Respiratory InfectionS in COPD (AERIS) is a longitudinal epidemiological study to assess how changes in the COPD airway microbiome contribute to the incidence and severity of AECOPD. Patients with COPD aged 40–85 are followed monthly for 2 years, and reviewed within 72 h of onset of symptoms of AECOPD. Exacerbations are detected using daily electronic diary cards. Blood, sputum, nasopharyngeal and urine samples are collected at prespecified timepoints. Molecular diagnostic and typing techniques are used to describe the dynamics of airway infection during AECOPD and stable disease, and associations with clinical outcome. This study aims to refine the case definition of AECOPD to reflect the possible microbiological aetiology. AERIS will assess the impact of AECOPD on health-related quality of life and healthcare resource utilisation, and the possible interactions between nutritional status, infection and immune responses. ETHICS AND DISSEMINATION: AERIS is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice, and has been approved by the institutional ethics and review board. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications. DISCUSSION: Few other studies have addressed the complexity of the microbiological and systemic components of COPD or employed real-time electronic tracking of symptoms to identify AECOPD and potential aetiological triggers. RESULTS: Results of AERIS will increase our understanding of the contribution of pathogens to AECOPD, potentially leading to new targeted therapeutic and preventative interventions. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01360398.",2014 Mar 7,"['Bourne, Simon', 'Cohet, Catherine', 'Kim, Viktoriya', 'Barton, Anna', 'Tuck, Andy', 'Aris, Emmanuel', 'Mesia-Vela, Sonia', 'Devaster, Jeanne-Marie', 'Ballou, W Ripley', 'Clarke, Stuart', 'Wilkinson, Tom']",BMJ Open,,,True
bbd9b38c4ba7adcd372e3720262d494614d0c174,PMC,"Acute Exacerbation and Respiratory InfectionS in COPD (AERIS): protocol for a prospective, observational cohort study",http://dx.doi.org/10.1136/bmjopen-2013-004546,PMC3948575,24607562,CC BY-NC,"INTRODUCTION: The aetiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) remains incompletely understood and strategies for treatment and prevention have not altered significantly for many years. Improved understanding of the role of respiratory pathogens in acute exacerbations of COPD (AECOPD) is required and the use of molecular microbiological techniques may lead to insights into host–pathogen interactions and the development of more targeted therapeutic approaches. METHODS AND ANALYSES: Acute Exacerbation and Respiratory InfectionS in COPD (AERIS) is a longitudinal epidemiological study to assess how changes in the COPD airway microbiome contribute to the incidence and severity of AECOPD. Patients with COPD aged 40–85 are followed monthly for 2 years, and reviewed within 72 h of onset of symptoms of AECOPD. Exacerbations are detected using daily electronic diary cards. Blood, sputum, nasopharyngeal and urine samples are collected at prespecified timepoints. Molecular diagnostic and typing techniques are used to describe the dynamics of airway infection during AECOPD and stable disease, and associations with clinical outcome. This study aims to refine the case definition of AECOPD to reflect the possible microbiological aetiology. AERIS will assess the impact of AECOPD on health-related quality of life and healthcare resource utilisation, and the possible interactions between nutritional status, infection and immune responses. ETHICS AND DISSEMINATION: AERIS is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice, and has been approved by the institutional ethics and review board. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications. DISCUSSION: Few other studies have addressed the complexity of the microbiological and systemic components of COPD or employed real-time electronic tracking of symptoms to identify AECOPD and potential aetiological triggers. RESULTS: Results of AERIS will increase our understanding of the contribution of pathogens to AECOPD, potentially leading to new targeted therapeutic and preventative interventions. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01360398.",2014 Mar 7,"['Bourne, Simon', 'Cohet, Catherine', 'Kim, Viktoriya', 'Barton, Anna', 'Tuck, Andy', 'Aris, Emmanuel', 'Mesia-Vela, Sonia', 'Devaster, Jeanne-Marie', 'Ballou, W Ripley', 'Clarke, Stuart', 'Wilkinson, Tom']",BMJ Open,,,False
bfa1dab8c91f41f59df39489115a8b2e19e537bf,PMC,Transcriptomic Characterization of the Novel Avian-Origin Influenza A (H7N9) Virus: Specific Host Response and Responses Intermediate between Avian (H5N1 and H7N7) and Human (H3N2) Viruses and Implications for Treatment Options,http://dx.doi.org/10.1128/mBio.01102-13,PMC3950506,24496798,CC BY-NC-SA,"A novel avian-origin H7N9 influenza A virus (IAV) emerged in China in 2013, causing mild to lethal human respiratory infections. H7N9 originated with multiple reassortment events between avian viruses and carries genetic markers of human adaptation. Determining whether H7N9 induces a host response closer to that with human or avian IAV is important in order to better characterize this emerging virus. Here we compared the human lung epithelial cell response to infection with A/Anhui/01/13 (H7N9) or highly pathogenic avian-origin H5N1, H7N7, or human seasonal H3N2 IAV. The transcriptomic response to H7N9 was highly specific to this strain but was more similar to the response to human H3N2 than to that to other avian IAVs. H7N9 and H3N2 both elicited responses related to eicosanoid signaling and chromatin modification, whereas H7N9 specifically induced genes regulating the cell cycle and transcription. Among avian IAVs, the response to H7N9 was closest to that elicited by H5N1 virus. Host responses common to H7N9 and the other avian viruses included the lack of induction of the antigen presentation pathway and reduced proinflammatory cytokine induction compared to that with H3N2. Repression of these responses could have an important impact on the immunogenicity and virulence of H7N9 in humans. Finally, using a genome-based drug repurposing approach, we identified several drugs predicted to regulate the host response to H7N9 that may act as potential antivirals, including several kinase inhibitors, as well as FDA-approved drugs, such as troglitazone and minocycline. Importantly, we validated that minocycline inhibited H7N9 replication in vitro, suggesting that our computational approach holds promise for identifying novel antivirals.",2014 Feb 4,"['Josset, Laurence', 'Zeng, Hui', 'Kelly, Sara M.', 'Tumpey, Terrence M.', 'Katze, Michael G.']",mBio,,,True
e99e13e33c49497d5d7de64d846216da6ad6d586,PMC,Transcriptomic Characterization of the Novel Avian-Origin Influenza A (H7N9) Virus: Specific Host Response and Responses Intermediate between Avian (H5N1 and H7N7) and Human (H3N2) Viruses and Implications for Treatment Options,http://dx.doi.org/10.1128/mBio.01102-13,PMC3950506,24496798,CC BY-NC-SA,"A novel avian-origin H7N9 influenza A virus (IAV) emerged in China in 2013, causing mild to lethal human respiratory infections. H7N9 originated with multiple reassortment events between avian viruses and carries genetic markers of human adaptation. Determining whether H7N9 induces a host response closer to that with human or avian IAV is important in order to better characterize this emerging virus. Here we compared the human lung epithelial cell response to infection with A/Anhui/01/13 (H7N9) or highly pathogenic avian-origin H5N1, H7N7, or human seasonal H3N2 IAV. The transcriptomic response to H7N9 was highly specific to this strain but was more similar to the response to human H3N2 than to that to other avian IAVs. H7N9 and H3N2 both elicited responses related to eicosanoid signaling and chromatin modification, whereas H7N9 specifically induced genes regulating the cell cycle and transcription. Among avian IAVs, the response to H7N9 was closest to that elicited by H5N1 virus. Host responses common to H7N9 and the other avian viruses included the lack of induction of the antigen presentation pathway and reduced proinflammatory cytokine induction compared to that with H3N2. Repression of these responses could have an important impact on the immunogenicity and virulence of H7N9 in humans. Finally, using a genome-based drug repurposing approach, we identified several drugs predicted to regulate the host response to H7N9 that may act as potential antivirals, including several kinase inhibitors, as well as FDA-approved drugs, such as troglitazone and minocycline. Importantly, we validated that minocycline inhibited H7N9 replication in vitro, suggesting that our computational approach holds promise for identifying novel antivirals.",2014 Feb 4,"['Josset, Laurence', 'Zeng, Hui', 'Kelly, Sara M.', 'Tumpey, Terrence M.', 'Katze, Michael G.']",mBio,,,False
fe7f2def173df98c879b01080e842f998b224571,PMC,Transcriptomic Characterization of the Novel Avian-Origin Influenza A (H7N9) Virus: Specific Host Response and Responses Intermediate between Avian (H5N1 and H7N7) and Human (H3N2) Viruses and Implications for Treatment Options,http://dx.doi.org/10.1128/mBio.01102-13,PMC3950506,24496798,CC BY-NC-SA,"A novel avian-origin H7N9 influenza A virus (IAV) emerged in China in 2013, causing mild to lethal human respiratory infections. H7N9 originated with multiple reassortment events between avian viruses and carries genetic markers of human adaptation. Determining whether H7N9 induces a host response closer to that with human or avian IAV is important in order to better characterize this emerging virus. Here we compared the human lung epithelial cell response to infection with A/Anhui/01/13 (H7N9) or highly pathogenic avian-origin H5N1, H7N7, or human seasonal H3N2 IAV. The transcriptomic response to H7N9 was highly specific to this strain but was more similar to the response to human H3N2 than to that to other avian IAVs. H7N9 and H3N2 both elicited responses related to eicosanoid signaling and chromatin modification, whereas H7N9 specifically induced genes regulating the cell cycle and transcription. Among avian IAVs, the response to H7N9 was closest to that elicited by H5N1 virus. Host responses common to H7N9 and the other avian viruses included the lack of induction of the antigen presentation pathway and reduced proinflammatory cytokine induction compared to that with H3N2. Repression of these responses could have an important impact on the immunogenicity and virulence of H7N9 in humans. Finally, using a genome-based drug repurposing approach, we identified several drugs predicted to regulate the host response to H7N9 that may act as potential antivirals, including several kinase inhibitors, as well as FDA-approved drugs, such as troglitazone and minocycline. Importantly, we validated that minocycline inhibited H7N9 replication in vitro, suggesting that our computational approach holds promise for identifying novel antivirals.",2014 Feb 4,"['Josset, Laurence', 'Zeng, Hui', 'Kelly, Sara M.', 'Tumpey, Terrence M.', 'Katze, Michael G.']",mBio,,,False
5a9ba9488d8fb41225b33452cd0fdf239828c404,PMC,Transcriptomic Characterization of the Novel Avian-Origin Influenza A (H7N9) Virus: Specific Host Response and Responses Intermediate between Avian (H5N1 and H7N7) and Human (H3N2) Viruses and Implications for Treatment Options,http://dx.doi.org/10.1128/mBio.01102-13,PMC3950506,24496798,CC BY-NC-SA,"A novel avian-origin H7N9 influenza A virus (IAV) emerged in China in 2013, causing mild to lethal human respiratory infections. H7N9 originated with multiple reassortment events between avian viruses and carries genetic markers of human adaptation. Determining whether H7N9 induces a host response closer to that with human or avian IAV is important in order to better characterize this emerging virus. Here we compared the human lung epithelial cell response to infection with A/Anhui/01/13 (H7N9) or highly pathogenic avian-origin H5N1, H7N7, or human seasonal H3N2 IAV. The transcriptomic response to H7N9 was highly specific to this strain but was more similar to the response to human H3N2 than to that to other avian IAVs. H7N9 and H3N2 both elicited responses related to eicosanoid signaling and chromatin modification, whereas H7N9 specifically induced genes regulating the cell cycle and transcription. Among avian IAVs, the response to H7N9 was closest to that elicited by H5N1 virus. Host responses common to H7N9 and the other avian viruses included the lack of induction of the antigen presentation pathway and reduced proinflammatory cytokine induction compared to that with H3N2. Repression of these responses could have an important impact on the immunogenicity and virulence of H7N9 in humans. Finally, using a genome-based drug repurposing approach, we identified several drugs predicted to regulate the host response to H7N9 that may act as potential antivirals, including several kinase inhibitors, as well as FDA-approved drugs, such as troglitazone and minocycline. Importantly, we validated that minocycline inhibited H7N9 replication in vitro, suggesting that our computational approach holds promise for identifying novel antivirals.",2014 Feb 4,"['Josset, Laurence', 'Zeng, Hui', 'Kelly, Sara M.', 'Tumpey, Terrence M.', 'Katze, Michael G.']",mBio,,,False
9e44cd081db94250577a7ce7c52acde7ad67eb7d,PMC,Transcriptomic Characterization of the Novel Avian-Origin Influenza A (H7N9) Virus: Specific Host Response and Responses Intermediate between Avian (H5N1 and H7N7) and Human (H3N2) Viruses and Implications for Treatment Options,http://dx.doi.org/10.1128/mBio.01102-13,PMC3950506,24496798,CC BY-NC-SA,"A novel avian-origin H7N9 influenza A virus (IAV) emerged in China in 2013, causing mild to lethal human respiratory infections. H7N9 originated with multiple reassortment events between avian viruses and carries genetic markers of human adaptation. Determining whether H7N9 induces a host response closer to that with human or avian IAV is important in order to better characterize this emerging virus. Here we compared the human lung epithelial cell response to infection with A/Anhui/01/13 (H7N9) or highly pathogenic avian-origin H5N1, H7N7, or human seasonal H3N2 IAV. The transcriptomic response to H7N9 was highly specific to this strain but was more similar to the response to human H3N2 than to that to other avian IAVs. H7N9 and H3N2 both elicited responses related to eicosanoid signaling and chromatin modification, whereas H7N9 specifically induced genes regulating the cell cycle and transcription. Among avian IAVs, the response to H7N9 was closest to that elicited by H5N1 virus. Host responses common to H7N9 and the other avian viruses included the lack of induction of the antigen presentation pathway and reduced proinflammatory cytokine induction compared to that with H3N2. Repression of these responses could have an important impact on the immunogenicity and virulence of H7N9 in humans. Finally, using a genome-based drug repurposing approach, we identified several drugs predicted to regulate the host response to H7N9 that may act as potential antivirals, including several kinase inhibitors, as well as FDA-approved drugs, such as troglitazone and minocycline. Importantly, we validated that minocycline inhibited H7N9 replication in vitro, suggesting that our computational approach holds promise for identifying novel antivirals.",2014 Feb 4,"['Josset, Laurence', 'Zeng, Hui', 'Kelly, Sara M.', 'Tumpey, Terrence M.', 'Katze, Michael G.']",mBio,,,False
4e1c469e04ba3430a9f6841338e496b279c1d0bd,PMC,Transcriptomic Characterization of the Novel Avian-Origin Influenza A (H7N9) Virus: Specific Host Response and Responses Intermediate between Avian (H5N1 and H7N7) and Human (H3N2) Viruses and Implications for Treatment Options,http://dx.doi.org/10.1128/mBio.01102-13,PMC3950506,24496798,CC BY-NC-SA,"A novel avian-origin H7N9 influenza A virus (IAV) emerged in China in 2013, causing mild to lethal human respiratory infections. H7N9 originated with multiple reassortment events between avian viruses and carries genetic markers of human adaptation. Determining whether H7N9 induces a host response closer to that with human or avian IAV is important in order to better characterize this emerging virus. Here we compared the human lung epithelial cell response to infection with A/Anhui/01/13 (H7N9) or highly pathogenic avian-origin H5N1, H7N7, or human seasonal H3N2 IAV. The transcriptomic response to H7N9 was highly specific to this strain but was more similar to the response to human H3N2 than to that to other avian IAVs. H7N9 and H3N2 both elicited responses related to eicosanoid signaling and chromatin modification, whereas H7N9 specifically induced genes regulating the cell cycle and transcription. Among avian IAVs, the response to H7N9 was closest to that elicited by H5N1 virus. Host responses common to H7N9 and the other avian viruses included the lack of induction of the antigen presentation pathway and reduced proinflammatory cytokine induction compared to that with H3N2. Repression of these responses could have an important impact on the immunogenicity and virulence of H7N9 in humans. Finally, using a genome-based drug repurposing approach, we identified several drugs predicted to regulate the host response to H7N9 that may act as potential antivirals, including several kinase inhibitors, as well as FDA-approved drugs, such as troglitazone and minocycline. Importantly, we validated that minocycline inhibited H7N9 replication in vitro, suggesting that our computational approach holds promise for identifying novel antivirals.",2014 Feb 4,"['Josset, Laurence', 'Zeng, Hui', 'Kelly, Sara M.', 'Tumpey, Terrence M.', 'Katze, Michael G.']",mBio,,,False
79c0f8dbc31024ca3901227a97df7d35341d5229,PMC,Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1,http://dx.doi.org/10.1128/mBio.00862-13,PMC3950510,24473128,CC BY-NC-SA,"Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency.",2014 Jan 28,"['Lennemann, Nicholas J.', 'Rhein, Bethany A.', 'Ndungo, Esther', 'Chandran, Kartik', 'Qiu, Xiangguo', 'Maury, Wendy']",mBio,,,True
43061772da7c84b389ab1e7ee98e110861120118,PMC,Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1,http://dx.doi.org/10.1128/mBio.00862-13,PMC3950510,24473128,CC BY-NC-SA,"Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency.",2014 Jan 28,"['Lennemann, Nicholas J.', 'Rhein, Bethany A.', 'Ndungo, Esther', 'Chandran, Kartik', 'Qiu, Xiangguo', 'Maury, Wendy']",mBio,,,False
ccc6bc36a3c03e601f1087d57908f2f375e59783,PMC,Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1,http://dx.doi.org/10.1128/mBio.00862-13,PMC3950510,24473128,CC BY-NC-SA,"Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency.",2014 Jan 28,"['Lennemann, Nicholas J.', 'Rhein, Bethany A.', 'Ndungo, Esther', 'Chandran, Kartik', 'Qiu, Xiangguo', 'Maury, Wendy']",mBio,,,False
0d55bd310d9d40f73cf1b905fe23c0b65ec25c81,PMC,Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1,http://dx.doi.org/10.1128/mBio.00862-13,PMC3950510,24473128,CC BY-NC-SA,"Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency.",2014 Jan 28,"['Lennemann, Nicholas J.', 'Rhein, Bethany A.', 'Ndungo, Esther', 'Chandran, Kartik', 'Qiu, Xiangguo', 'Maury, Wendy']",mBio,,,False
e6dcc692a39166e78808eeb7486b0fa926174c07,PMC,Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1,http://dx.doi.org/10.1128/mBio.00862-13,PMC3950510,24473128,CC BY-NC-SA,"Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency.",2014 Jan 28,"['Lennemann, Nicholas J.', 'Rhein, Bethany A.', 'Ndungo, Esther', 'Chandran, Kartik', 'Qiu, Xiangguo', 'Maury, Wendy']",mBio,,,False
60f4f8e1af880ec638659b4660cea395062565a4,PMC,Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1,http://dx.doi.org/10.1128/mBio.00862-13,PMC3950510,24473128,CC BY-NC-SA,"Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency.",2014 Jan 28,"['Lennemann, Nicholas J.', 'Rhein, Bethany A.', 'Ndungo, Esther', 'Chandran, Kartik', 'Qiu, Xiangguo', 'Maury, Wendy']",mBio,,,False
9e9252f52a3b50a858c8a9e437ff288a68be64e1,PMC,Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1,http://dx.doi.org/10.1128/mBio.00862-13,PMC3950510,24473128,CC BY-NC-SA,"Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency.",2014 Jan 28,"['Lennemann, Nicholas J.', 'Rhein, Bethany A.', 'Ndungo, Esther', 'Chandran, Kartik', 'Qiu, Xiangguo', 'Maury, Wendy']",mBio,,,False
c1bbd91b5d52d7cfd6231129925e7b841dfe63b2,PMC,Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1,http://dx.doi.org/10.1128/mBio.00862-13,PMC3950510,24473128,CC BY-NC-SA,"Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency.",2014 Jan 28,"['Lennemann, Nicholas J.', 'Rhein, Bethany A.', 'Ndungo, Esther', 'Chandran, Kartik', 'Qiu, Xiangguo', 'Maury, Wendy']",mBio,,,False
1bc087e34cba1b773c0544a4e02cb494e3b07bc0,PMC,Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1,http://dx.doi.org/10.1128/mBio.00862-13,PMC3950510,24473128,CC BY-NC-SA,"Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency.",2014 Jan 28,"['Lennemann, Nicholas J.', 'Rhein, Bethany A.', 'Ndungo, Esther', 'Chandran, Kartik', 'Qiu, Xiangguo', 'Maury, Wendy']",mBio,,,False
ebb19de2179e5840cccd7113ea408c1bc66e26d2,PMC,Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1,http://dx.doi.org/10.1128/mBio.00862-13,PMC3950510,24473128,CC BY-NC-SA,"Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency.",2014 Jan 28,"['Lennemann, Nicholas J.', 'Rhein, Bethany A.', 'Ndungo, Esther', 'Chandran, Kartik', 'Qiu, Xiangguo', 'Maury, Wendy']",mBio,,,False
2559cb0b4a2175212495ab7d44d9305db4a06c05,PMC,Structural basis for the regulatory function of a complex zinc-binding domain in a replicative arterivirus helicase resembling a nonsense-mediated mRNA decay helicase,http://dx.doi.org/10.1093/nar/gkt1310,PMC3950703,24369429,CC BY-NC,"All positive-stranded RNA viruses with genomes >∼7 kb encode helicases, which generally are poorly characterized. The core of the nidovirus superfamily 1 helicase (HEL1) is associated with a unique N-terminal zinc-binding domain (ZBD) that was previously implicated in helicase regulation, genome replication and subgenomic mRNA synthesis. The high-resolution structure of the arterivirus helicase (nsp10), alone and in complex with a polynucleotide substrate, now provides first insights into the structural basis for nidovirus helicase function. A previously uncharacterized domain 1B connects HEL1 domains 1A and 2A to a long linker of ZBD, which further consists of a novel RING-like module and treble-clef zinc finger, together coordinating three Zn atoms. On substrate binding, major conformational changes were evident outside the HEL1 domains, notably in domain 1B. Structural characterization, mutagenesis and biochemistry revealed that helicase activity depends on the extensive relay of interactions between the ZBD and HEL1 domains. The arterivirus helicase structurally resembles the cellular Upf1 helicase, suggesting that nidoviruses may also use their helicases for post-transcriptional quality control of their large RNA genomes.",2014 Mar 24,"['Deng, Zengqin', 'Lehmann, Kathleen C.', 'Li, Xiaorong', 'Feng, Chong', 'Wang, Guoqiang', 'Zhang, Qi', 'Qi, Xiaoxuan', 'Yu, Lin', 'Zhang, Xingliang', 'Feng, Wenhai', 'Wu, Wei', 'Gong, Peng', 'Tao, Ye', 'Posthuma, Clara C.', 'Snijder, Eric J.', 'Gorbalenya, Alexander E.', 'Chen, Zhongzhou']",Nucleic Acids Res,,,True
0ce1f213337247a67628f95cf699bdabddc94d9c,PMC,"Inhibition of translation by IFIT family members is determined by their ability to interact selectively with the 5′-terminal regions of cap0-, cap1- and 5′ppp- mRNAs",http://dx.doi.org/10.1093/nar/gkt1321,PMC3950709,24371270,CC BY-NC,"Ribosomal recruitment of cellular mRNAs depends on binding of eIF4F to the mRNA’s 5′-terminal ‘cap’. The minimal ‘cap0’ consists of N7-methylguanosine linked to the first nucleotide via a 5′-5′ triphosphate (ppp) bridge. Cap0 is further modified by 2′-O-methylation of the next two riboses, yielding ‘cap1’ (m7GpppNmN) and ‘cap2’ (m7GpppNmNm). However, some viral RNAs lack 2′-O-methylation, whereas others contain only ppp- at their 5′-end. Interferon-induced proteins with tetratricopeptide repeats (IFITs) are highly expressed effectors of innate immunity that inhibit viral replication by incompletely understood mechanisms. Here, we investigated the ability of IFIT family members to interact with cap1-, cap0- and 5′ppp- mRNAs and inhibit their translation. IFIT1 and IFIT1B showed very high affinity to cap-proximal regions of cap0-mRNAs (K(1/2,app) ∼9 to 23 nM). The 2′-O-methylation abrogated IFIT1/mRNA interaction, whereas IFIT1B retained the ability to bind cap1-mRNA, albeit with reduced affinity (K(1/2,app) ∼450 nM). The 5′-terminal regions of 5′ppp-mRNAs were recognized by IFIT5 (K(1/2,app) ∼400 nM). The activity of individual IFITs in inhibiting initiation on a specific mRNA was determined by their ability to interact with its 5′-terminal region: IFIT1 and IFIT1B efficiently outcompeted eIF4F and abrogated initiation on cap0-mRNAs, whereas inhibition on cap1- and 5′ppp- mRNAs by IFIT1B and IFIT5 was weaker and required higher protein concentrations.",2014 Mar 25,"['Kumar, Parimal', 'Sweeney, Trevor R.', 'Skabkin, Maxim A.', 'Skabkina, Olga V.', 'Hellen, Christopher U. T.', 'Pestova, Tatyana V.']",Nucleic Acids Res,,,True
053015b1322bd1ab63323e036c6ce37cfe62bde2,PMC,"Inhibition of translation by IFIT family members is determined by their ability to interact selectively with the 5′-terminal regions of cap0-, cap1- and 5′ppp- mRNAs",http://dx.doi.org/10.1093/nar/gkt1321,PMC3950709,24371270,CC BY-NC,"Ribosomal recruitment of cellular mRNAs depends on binding of eIF4F to the mRNA’s 5′-terminal ‘cap’. The minimal ‘cap0’ consists of N7-methylguanosine linked to the first nucleotide via a 5′-5′ triphosphate (ppp) bridge. Cap0 is further modified by 2′-O-methylation of the next two riboses, yielding ‘cap1’ (m7GpppNmN) and ‘cap2’ (m7GpppNmNm). However, some viral RNAs lack 2′-O-methylation, whereas others contain only ppp- at their 5′-end. Interferon-induced proteins with tetratricopeptide repeats (IFITs) are highly expressed effectors of innate immunity that inhibit viral replication by incompletely understood mechanisms. Here, we investigated the ability of IFIT family members to interact with cap1-, cap0- and 5′ppp- mRNAs and inhibit their translation. IFIT1 and IFIT1B showed very high affinity to cap-proximal regions of cap0-mRNAs (K(1/2,app) ∼9 to 23 nM). The 2′-O-methylation abrogated IFIT1/mRNA interaction, whereas IFIT1B retained the ability to bind cap1-mRNA, albeit with reduced affinity (K(1/2,app) ∼450 nM). The 5′-terminal regions of 5′ppp-mRNAs were recognized by IFIT5 (K(1/2,app) ∼400 nM). The activity of individual IFITs in inhibiting initiation on a specific mRNA was determined by their ability to interact with its 5′-terminal region: IFIT1 and IFIT1B efficiently outcompeted eIF4F and abrogated initiation on cap0-mRNAs, whereas inhibition on cap1- and 5′ppp- mRNAs by IFIT1B and IFIT5 was weaker and required higher protein concentrations.",2014 Mar 25,"['Kumar, Parimal', 'Sweeney, Trevor R.', 'Skabkin, Maxim A.', 'Skabkina, Olga V.', 'Hellen, Christopher U. T.', 'Pestova, Tatyana V.']",Nucleic Acids Res,,,False
2bae24fa42f6bd7e9a241b4456296f3af0ee4b2c,PMC,Glioblastoma extracellular vesicles: reservoirs of potential biomarkers,http://dx.doi.org/10.2147/PGPM.S39768,PMC3952682,24634586,CC BY-NC,"Glioblastoma multiforme (GBM) is the most frequent and most devastating of the primary central nervous system tumors, with few patients living beyond 2 years postdiagnosis. The damage caused by the disease and our treatments for the patients often leave them physically and cognitively debilitated. Generally, GBMs appear after very short clinical histories and are discovered by imaging (using magnetic resonance imaging [MRI]), and the diagnosis is validated by pathology, following surgical resection. The treatment response and diagnosis of tumor recurrence are also tracked by MRI, but there are numerous problems encountered with these monitoring modalities, such as ambiguous interpretation and forms of pseudoprogression. Diagnostic, prognostic, and predictive biomarkers would be an immense boon in following treatment schemes and in determining recurrence, which often requires an invasive intracranial biopsy to verify imaging data. Extracellular vesicles (EVs) are stable, membrane-enclosed, virus-sized particles released from either the cell surface or from endosomal pathways that lead to the systemic release of EVs into accessible biofluids, such as serum/plasma, urine, cerebrospinal fluid, and saliva. EVs carry a wide variety of proteins, nucleic acids, lipids, and other metabolites, with many common features but with enough individuality to be able to identify the cell of origin of the vesicles. These components, if properly interrogated, could allow for the identification of tumor-derived EVs in biofluids, indicating tumor progression, relapse, or treatment failure. That knowledge would allow clinicians to continue with treatment regimens that were actually effective or to change course if the therapies were failing. Here, we review the features of GBM EVs, in terms of EV content and activities that may lead to the use of EVs as serially accessible biomarkers for diagnosis and treatment response in neuro-oncology.",2014 Feb 13,"['Redzic, Jasmina S', 'Ung, Timothy H', 'Graner, Michael W']",Pharmgenomics Pers Med,,,True
fc6489e42c4a336fd64bd4b82639037087aa60fe,PMC,Characterization of a Novel Influenza Virus in Cattle and Swine: Proposal for a New Genus in the Orthomyxoviridae Family,http://dx.doi.org/10.1128/mBio.00031-14,PMC3958797,24595369,CC BY-NC-SA,"We have recently reported the isolation of a novel virus, provisionally designated C/swine/Oklahoma/1334/2011 (C/OK), with 50% overall homology to human influenza C viruses (ICV), from a pig in Oklahoma. Deep RNA sequencing of C/OK virus found a matrix 1 (M1) protein expression strategy that differed from that of ICV. The novelty of C/OK virus prompted us to investigate whether C/OK virus could exist in a nonswine species. Significantly, we found that C/OK virus was widespread in U.S. bovine herds, as demonstrated by reverse transcription (RT)-PCR and serological assays. Genome sequencing of three bovine viruses isolated from two herds in different states further confirmed these findings. To determine whether swine/bovine C/OK viruses can undergo reassortment with human ICV, and to clarify the taxonomic status of C/OK, in vitro reassortment and serological typing by agar gel immunodiffusion (AGID) were conducted. In vitro reassortment using two human ICV and two swine and bovine C/OK viruses demonstrated that human ICV and C/OK viruses were unable to reassort and produce viable progeny. Antigenically, no cross-recognition of detergent split virions was observed in AGID between human and nonhuman viruses by using polyclonal antibodies that were reactive to cognate antigens. Taken together, these results demonstrate that C/OK virus is genetically and antigenically distinct from ICV. The classification of the new virus in a separate genus of the Orthomyxoviridae family is proposed. The finding of C/OK virus in swine and bovine indicates that this new virus may spread and establish infection in other mammals, including humans.",2014 Mar 4,"['Hause, Ben M.', 'Collin, Emily A.', 'Liu, Runxia', 'Huang, Bing', 'Sheng, Zizhang', 'Lu, Wuxun', 'Wang, Dan', 'Nelson, Eric A.', 'Li, Feng']",mBio,,,True
72e66855dca70375474400a4bdfafed8135eae4c,PMC,Characterization of a Novel Influenza Virus in Cattle and Swine: Proposal for a New Genus in the Orthomyxoviridae Family,http://dx.doi.org/10.1128/mBio.00031-14,PMC3958797,24595369,CC BY-NC-SA,"We have recently reported the isolation of a novel virus, provisionally designated C/swine/Oklahoma/1334/2011 (C/OK), with 50% overall homology to human influenza C viruses (ICV), from a pig in Oklahoma. Deep RNA sequencing of C/OK virus found a matrix 1 (M1) protein expression strategy that differed from that of ICV. The novelty of C/OK virus prompted us to investigate whether C/OK virus could exist in a nonswine species. Significantly, we found that C/OK virus was widespread in U.S. bovine herds, as demonstrated by reverse transcription (RT)-PCR and serological assays. Genome sequencing of three bovine viruses isolated from two herds in different states further confirmed these findings. To determine whether swine/bovine C/OK viruses can undergo reassortment with human ICV, and to clarify the taxonomic status of C/OK, in vitro reassortment and serological typing by agar gel immunodiffusion (AGID) were conducted. In vitro reassortment using two human ICV and two swine and bovine C/OK viruses demonstrated that human ICV and C/OK viruses were unable to reassort and produce viable progeny. Antigenically, no cross-recognition of detergent split virions was observed in AGID between human and nonhuman viruses by using polyclonal antibodies that were reactive to cognate antigens. Taken together, these results demonstrate that C/OK virus is genetically and antigenically distinct from ICV. The classification of the new virus in a separate genus of the Orthomyxoviridae family is proposed. The finding of C/OK virus in swine and bovine indicates that this new virus may spread and establish infection in other mammals, including humans.",2014 Mar 4,"['Hause, Ben M.', 'Collin, Emily A.', 'Liu, Runxia', 'Huang, Bing', 'Sheng, Zizhang', 'Lu, Wuxun', 'Wang, Dan', 'Nelson, Eric A.', 'Li, Feng']",mBio,,,False
117231a6c2443af20fc807b92118753b4b91b644,PMC,Characterization of a Novel Influenza Virus in Cattle and Swine: Proposal for a New Genus in the Orthomyxoviridae Family,http://dx.doi.org/10.1128/mBio.00031-14,PMC3958797,24595369,CC BY-NC-SA,"We have recently reported the isolation of a novel virus, provisionally designated C/swine/Oklahoma/1334/2011 (C/OK), with 50% overall homology to human influenza C viruses (ICV), from a pig in Oklahoma. Deep RNA sequencing of C/OK virus found a matrix 1 (M1) protein expression strategy that differed from that of ICV. The novelty of C/OK virus prompted us to investigate whether C/OK virus could exist in a nonswine species. Significantly, we found that C/OK virus was widespread in U.S. bovine herds, as demonstrated by reverse transcription (RT)-PCR and serological assays. Genome sequencing of three bovine viruses isolated from two herds in different states further confirmed these findings. To determine whether swine/bovine C/OK viruses can undergo reassortment with human ICV, and to clarify the taxonomic status of C/OK, in vitro reassortment and serological typing by agar gel immunodiffusion (AGID) were conducted. In vitro reassortment using two human ICV and two swine and bovine C/OK viruses demonstrated that human ICV and C/OK viruses were unable to reassort and produce viable progeny. Antigenically, no cross-recognition of detergent split virions was observed in AGID between human and nonhuman viruses by using polyclonal antibodies that were reactive to cognate antigens. Taken together, these results demonstrate that C/OK virus is genetically and antigenically distinct from ICV. The classification of the new virus in a separate genus of the Orthomyxoviridae family is proposed. The finding of C/OK virus in swine and bovine indicates that this new virus may spread and establish infection in other mammals, including humans.",2014 Mar 4,"['Hause, Ben M.', 'Collin, Emily A.', 'Liu, Runxia', 'Huang, Bing', 'Sheng, Zizhang', 'Lu, Wuxun', 'Wang, Dan', 'Nelson, Eric A.', 'Li, Feng']",mBio,,,False
15a052b427ec3a36fb9d65b19a5a49fae91f3b7e,PMC,Characterization of a Novel Influenza Virus in Cattle and Swine: Proposal for a New Genus in the Orthomyxoviridae Family,http://dx.doi.org/10.1128/mBio.00031-14,PMC3958797,24595369,CC BY-NC-SA,"We have recently reported the isolation of a novel virus, provisionally designated C/swine/Oklahoma/1334/2011 (C/OK), with 50% overall homology to human influenza C viruses (ICV), from a pig in Oklahoma. Deep RNA sequencing of C/OK virus found a matrix 1 (M1) protein expression strategy that differed from that of ICV. The novelty of C/OK virus prompted us to investigate whether C/OK virus could exist in a nonswine species. Significantly, we found that C/OK virus was widespread in U.S. bovine herds, as demonstrated by reverse transcription (RT)-PCR and serological assays. Genome sequencing of three bovine viruses isolated from two herds in different states further confirmed these findings. To determine whether swine/bovine C/OK viruses can undergo reassortment with human ICV, and to clarify the taxonomic status of C/OK, in vitro reassortment and serological typing by agar gel immunodiffusion (AGID) were conducted. In vitro reassortment using two human ICV and two swine and bovine C/OK viruses demonstrated that human ICV and C/OK viruses were unable to reassort and produce viable progeny. Antigenically, no cross-recognition of detergent split virions was observed in AGID between human and nonhuman viruses by using polyclonal antibodies that were reactive to cognate antigens. Taken together, these results demonstrate that C/OK virus is genetically and antigenically distinct from ICV. The classification of the new virus in a separate genus of the Orthomyxoviridae family is proposed. The finding of C/OK virus in swine and bovine indicates that this new virus may spread and establish infection in other mammals, including humans.",2014 Mar 4,"['Hause, Ben M.', 'Collin, Emily A.', 'Liu, Runxia', 'Huang, Bing', 'Sheng, Zizhang', 'Lu, Wuxun', 'Wang, Dan', 'Nelson, Eric A.', 'Li, Feng']",mBio,,,False
7e1d33cf80c62e4e7de67f8beb280c86266b887f,PMC,Highly dynamic animal contact network and implications on disease transmission,http://dx.doi.org/10.1038/srep04472,PMC3966050,24667241,CC BY-NC-ND,"Contact patterns among hosts are considered as one of the most critical factors contributing to unequal pathogen transmission. Consequently, networks have been widely applied in infectious disease modeling. However most studies assume static network structure due to lack of accurate observation and appropriate analytic tools. In this study we used high temporal and spatial resolution animal position data to construct a high-resolution contact network relevant to infectious disease transmission. The animal contact network aggregated at hourly level was highly variable and dynamic within and between days, for both network structure (network degree distribution) and individual rank of degree distribution in the network (degree order). We integrated network degree distribution and degree order heterogeneities with a commonly used contact-based, directly transmitted disease model to quantify the effect of these two sources of heterogeneity on the infectious disease dynamics. Four conditions were simulated based on the combination of these two heterogeneities. Simulation results indicated that disease dynamics and individual contribution to new infections varied substantially among these four conditions under both parameter settings. Changes in the contact network had a greater effect on disease dynamics for pathogens with smaller basic reproduction number (i.e. R(0) < 2).",2014 Mar 26,"['Chen, Shi', 'White, Brad J.', 'Sanderson, Michael W.', 'Amrine, David E.', 'Ilany, Amiyaal', 'Lanzas, Cristina']",Sci Rep,,,True
4ea72d2d8c2d40ee4bed64f2e0d1c253cf76b7f9,PMC,Highly dynamic animal contact network and implications on disease transmission,http://dx.doi.org/10.1038/srep04472,PMC3966050,24667241,CC BY-NC-ND,"Contact patterns among hosts are considered as one of the most critical factors contributing to unequal pathogen transmission. Consequently, networks have been widely applied in infectious disease modeling. However most studies assume static network structure due to lack of accurate observation and appropriate analytic tools. In this study we used high temporal and spatial resolution animal position data to construct a high-resolution contact network relevant to infectious disease transmission. The animal contact network aggregated at hourly level was highly variable and dynamic within and between days, for both network structure (network degree distribution) and individual rank of degree distribution in the network (degree order). We integrated network degree distribution and degree order heterogeneities with a commonly used contact-based, directly transmitted disease model to quantify the effect of these two sources of heterogeneity on the infectious disease dynamics. Four conditions were simulated based on the combination of these two heterogeneities. Simulation results indicated that disease dynamics and individual contribution to new infections varied substantially among these four conditions under both parameter settings. Changes in the contact network had a greater effect on disease dynamics for pathogens with smaller basic reproduction number (i.e. R(0) < 2).",2014 Mar 26,"['Chen, Shi', 'White, Brad J.', 'Sanderson, Michael W.', 'Amrine, David E.', 'Ilany, Amiyaal', 'Lanzas, Cristina']",Sci Rep,,,False
39988cf0ce9b1ea1e63e9c3c15de51a9c87fc376,PMC,Tackling the Global Challenge: Humanitarian Catastrophes,http://dx.doi.org/10.5811/westjem.2013.12.20125,PMC3966462,24672618,CC BY-NC,"“Humanitarian catastrophes,” conflicts and calamities generating both widespread human suffering and destructive events, require a wide range of emergency resources. This paper answers a number of questions that humanitarian catastrophes generate: Why and how do the most-developed countries—those with the resources, capabilities, and willingness to help—intervene in specific types of disasters? What ethical and legal guidelines shape our interventions? How well do we achieve our goals? It then suggests a number of changes to improve humanitarian responses, including better NGO-government cooperation, increased research on the best disaster response methods, clarification of the criteria and roles for humanitarian (military) interventions, and development of post-2015 Millennium Development Goals with more accurate progress measures.",2014 Mar,"Iserson, Kenneth V.",West J Emerg Med,,,True
6fe03a33f128c5118c47544910549a695da57d08,PMC,Interactome Mapping: Using Protein Microarray Technology to Reconstruct Diverse Protein Networks,http://dx.doi.org/10.1016/j.gpb.2012.12.005,PMC3968920,23395178,CC BY-NC-SA,"A major focus of systems biology is to characterize interactions between cellular components, in order to develop an accurate picture of the intricate networks within biological systems. Over the past decade, protein microarrays have greatly contributed to advances in proteomics and are becoming an important platform for systems biology. Protein microarrays are highly flexible, ranging from large-scale proteome microarrays to smaller customizable microarrays, making the technology amenable for detection of a broad spectrum of biochemical properties of proteins. In this article, we will focus on the numerous studies that have utilized protein microarrays to reconstruct biological networks including protein–DNA interactions, posttranslational protein modifications (PTMs), lectin–glycan recognition, pathogen–host interactions and hierarchical signaling cascades. The diversity in applications allows for integration of interaction data from numerous molecular classes and cellular states, providing insight into the structure of complex biological systems. We will also discuss emerging applications and future directions of protein microarray technology in the global frontier.",2013 Feb 17,"['Uzoma, Ijeoma', 'Zhu, Heng']",Genomics Proteomics Bioinformatics,,,False
0f34670b6327305bb3d66de79d1aa96a5d8de2b2,PMC,An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination,http://dx.doi.org/10.2147/IJN.S59924,PMC3969340,24711701,CC BY-NC,"Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating respiratory disease of pigs. The disease is caused by the PRRS virus (PRRSV), an Arterivirus which is a highly mutating RNA virus. Widely used modified live PRRSV vaccines have failed to prevent PRRS outbreaks and reinfections; moreover, safety of the live virus vaccines is questionable. Though poorly immunogenic, inactivated PRRSV vaccine is safe. The PRRSV infects primarily the lung macrophages. Therefore, we attempted to strengthen the immunogenicity of inactivated/killed PRRSV vaccine antigens (KAg), especially in the pig respiratory system, through: 1) entrapping the KAg in biodegradable poly(lactic-co-glycolic acid) nanoparticles (NP-KAg); 2) coupling the NP-KAg with a potent mucosal adjuvant, whole cell lysate of Mycobacterium tuberculosis (M. tb WCL); and 3) delivering the vaccine formulation twice intranasally to growing pigs. We have previously shown that a single dose of NP-KAg partially cleared the challenged heterologous PRRSV. Recently, we reported that NP-KAg coupled with unentrapped M. tb WCL significantly cleared the viremia of challenged heterologous PRRSV. Since PRRSV is primarily a lung disease, our goal in this study was to investigate lung viral load and various immune correlates of protection at the lung mucosal surfaces and its parenchyma in vaccinated heterologous PRRSV-challenged pigs. Our results indicated that out of five different vaccine-adjuvant formulations, the combination of NP-KAg and unentrapped M. tb WCL significantly cleared detectable replicating infective PRRSV with a tenfold reduction in viral RNA load in the lungs, associated with substantially reduced gross and microscopic lung pathology. Immunologically, strong humoral (enhanced virus neutralization titers by high avidity antibodies) and cell-mediated immune responses (augmented population of interferon-γ secreting CD4(+) and CD8(+) lymphocytes and reduced secretion of immunosuppressive cytokines) in the lungs were observed. In conclusion, combination of NP-KAg and soluble M. tb WCL elicits broadly cross-protective anti-PRRSV immunity in the pig respiratory system.",2014 Mar 24,"['Binjawadagi, Basavaraj', 'Dwivedi, Varun', 'Manickam, Cordelia', 'Ouyang, Kang', 'Torrelles, Jordi B', 'Renukaradhya, Gourapura J']",Int J Nanomedicine,,,True
974de2ddd9575e32633a8038613f4e8f4333a70f,PMC,Chloroquine use improves dengue-related symptoms,http://dx.doi.org/10.1590/0074-0276108052013010,PMC3970591,23903975,CC BY-NC,"Dengue is the most important arboviral disease in the world. As chloroquine, an antimalarial agent, has shown some antiviral effects, this study evaluated its effect in patients with dengue. A randomised, double-blind study was performed by administering chloroquine or placebo for three days to 129 patients with dengue-related symptoms. Of these patients, 37 were confirmed as having dengue and completed the study; in total, 19 dengue patients received chloroquine and 18 received placebo. There was no significant difference in the duration of the disease or the degree and days of fever. However, 12 patients (63%) with confirmed dengue reported a substantial decrease in pain intensity and a great improvement in their ability to perform daily activities (p = 0.0004) while on the medication and the symptoms returned immediately after these patients stopped taking the medication. The same effect was not observed in patients with diseases other than dengue. Therefore, this study shows that patients with dengue treated with chloroquine had an improvement in their quality of life and were able to resume their daily activities. However, as chloroquine did not alter the duration of the disease or the intensity and days of fever, further studies are necessary to confirm the clinical effects and to assess the side effects of chloroquine in dengue patients.",2013 Aug,"['Borges, Marcos Carvalho', 'Castro, Luiza Antunes', 'da Fonseca, Benedito Antonio Lopes']",Mem Inst Oswaldo Cruz,,,True
bfffc49744be05481a8a3d0266b38c8c2a816f14,PMC,Shrinkage of Genome Size in a Plant RNA Virus upon Transfer of an Essential Viral Gene into the Host Genome,http://dx.doi.org/10.1093/gbe/evu036,PMC3971587,24558257,CC BY-NC,"Nonretroviral integrated RNA viruses (NIRVs) are genes of nonretroviral RNA viruses found in the genomes of many eukaryotic organisms. NIRVs are thought to sometimes confer virus resistance, meaning that they could impact spread of the virus in the host population. However, a NIRV that is expressed may also impact the evolution of virus populations within host organisms. Here, we experimentally addressed the evolution of a virus in a host expressing a NIRV using Tobacco etch virus (TEV), a plant RNA virus, and transgenic tobacco plants expressing its replicase, NIb. We found that a virus missing the NIb gene, TEV-ΔNIb, which is incapable of autonomous replication in wild-type plants, had a higher fitness than the full-length TEV in the transgenic plants. Moreover, when the full-length TEV was evolved by serial passages in transgenic plants, we observed genomic deletions within NIb—and in some cases the adjacent cistrons—starting from the first passage. When we passaged TEV and TEV-ΔNIb in transgenic plants, we found mutations in proteolytic sites, but these only occurred in TEV-ΔNIb lineages, suggesting the adaptation of polyprotein processing to altered NIb expression. These results raise the possibility that NIRV expression can indeed induce the deletion of the corresponding genes in the viral genome, resulting in the formation of viruses that are replication defective in hosts that do not express the same NIRV. Moreover, virus genome evolution was contingent upon the deletion of the viral replicase, suggesting NIRV expression could also alter patterns of virus evolution.",2014 Feb 20,"['Tromas, Nicolas', 'Zwart, Mark P.', 'Forment, Javier', 'Elena, Santiago F.']",Genome Biol Evol,,,True
af692c04e4987b4ba6c5e216557026adc7605550,PMC,Shrinkage of Genome Size in a Plant RNA Virus upon Transfer of an Essential Viral Gene into the Host Genome,http://dx.doi.org/10.1093/gbe/evu036,PMC3971587,24558257,CC BY-NC,"Nonretroviral integrated RNA viruses (NIRVs) are genes of nonretroviral RNA viruses found in the genomes of many eukaryotic organisms. NIRVs are thought to sometimes confer virus resistance, meaning that they could impact spread of the virus in the host population. However, a NIRV that is expressed may also impact the evolution of virus populations within host organisms. Here, we experimentally addressed the evolution of a virus in a host expressing a NIRV using Tobacco etch virus (TEV), a plant RNA virus, and transgenic tobacco plants expressing its replicase, NIb. We found that a virus missing the NIb gene, TEV-ΔNIb, which is incapable of autonomous replication in wild-type plants, had a higher fitness than the full-length TEV in the transgenic plants. Moreover, when the full-length TEV was evolved by serial passages in transgenic plants, we observed genomic deletions within NIb—and in some cases the adjacent cistrons—starting from the first passage. When we passaged TEV and TEV-ΔNIb in transgenic plants, we found mutations in proteolytic sites, but these only occurred in TEV-ΔNIb lineages, suggesting the adaptation of polyprotein processing to altered NIb expression. These results raise the possibility that NIRV expression can indeed induce the deletion of the corresponding genes in the viral genome, resulting in the formation of viruses that are replication defective in hosts that do not express the same NIRV. Moreover, virus genome evolution was contingent upon the deletion of the viral replicase, suggesting NIRV expression could also alter patterns of virus evolution.",2014 Feb 20,"['Tromas, Nicolas', 'Zwart, Mark P.', 'Forment, Javier', 'Elena, Santiago F.']",Genome Biol Evol,,,False
2159d7f128a1995e7131a8d4f036fcb3cec6e332,PMC,Methamphetamine induces autophagy as a pro-survival response against apoptotic endothelial cell death through the Kappa opioid receptor,http://dx.doi.org/10.1038/cddis.2014.64,PMC3973232,24603327,CC BY-NC-ND,"Methamphetamine (METH) is a psychostimulant with high abuse potential and severe neurotoxicity. Recent studies in animal models have indicated that METH can impair the blood–brain barrier (BBB), suggesting that some of the neurotoxic effects resulting from METH abuse could be due to barrier disruption. We report here that while chronic exposure to METH disrupts barrier function of primary human brain microvascular endothelial cells (HBMECs) and human umbilical vein endothelial cells (HUVECs), an early pro-survival response is observed following acute exposure by induction of autophagic mechanisms. Acute METH exposure induces an early increase in Beclin1 and LC3 recruitment. This is mediated through inactivation of the protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/p70S6K pathway, and upregulation of the ERK1/2. Blockade of Kappa opioid receptor (KOR), and treatment with autophagic inhibitors accelerated METH-induced apoptosis, suggesting that the early autophagic response is a survival mechanism for endothelial cells and is mediated through the kappa opioid receptor. Our studies indicate that kappa opioid receptor can be therapeutically exploited for attenuating METH-induced BBB dysfunction.",2014 Mar 6,"['Ma, J', 'Wan, J', 'Meng, J', 'Banerjee, S', 'Ramakrishnan, S', 'Roy, S']",Cell Death Dis,,,True
04e156a83cb3b0b2da2ed07eec1a669be53575b5,PMC,"An overview of calf diarrhea - infectious etiology, diagnosis, and intervention",http://dx.doi.org/10.4142/jvs.2014.15.1.1,PMC3973752,24378583,CC BY-NC,"Calf diarrhea is a commonly reported disease in young animals, and still a major cause of productivity and economic loss to cattle producers worldwide. In the report of the 2007 National Animal Health Monitoring System for U.S. dairy, half of the deaths among unweaned calves was attributed to diarrhea. Multiple pathogens are known or postulated to cause or contribute to calf diarrhea development. Other factors including both the environment and management practices influence disease severity or outcomes. The multifactorial nature of calf diarrhea makes this disease hard to control effectively in modern cow-calf operations. The purpose of this review is to provide a better understanding of a) the ecology and pathogenesis of well-known and potential bovine enteric pathogens implicated in calf diarrhea, b) describe diagnostic tests used to detect various enteric pathogens along with their pros and cons, and c) propose improved intervention strategies for treating calf diarrhea.",2014 Mar 19,"['Cho, Yong-il', 'Yoon, Kyoung-Jin']",J Vet Sci,,,True
b6ee8c246cde8fc8ab8df4d3e287ca0ca7679532,PMC,Development and clinical evaluation of a rapid diagnostic kit for feline leukemia virus infection,http://dx.doi.org/10.4142/jvs.2014.15.1.91,PMC3973770,24136209,CC BY-NC,"Feline leukemia virus (FeLV) causes a range of neoplastic and degenerative diseases in cats. To obtain a more sensitive and convenient diagnosis of the disease, we prepared monoclonal antibodies specific for the FeLV p27 to develop a rapid diagnostic test with enhanced sensitivity and specificity. Among these antibodies, we identified two clones (hybridomas 8F8B5 and 8G7D1) that specifically bound to FeLV and were very suitable for a diagnostic kit. The affinity constants for 8F8B5 and 8G7D1 were 0.35 × 10(9) and 0.86 × 10(9), respectively. To investigate the diagnostic abilities of the rapid kit using these antibodies, we performed several clinical studies. Assessment of analytical sensitivity revealed that the detection threshold of the rapid diagnostic test was 2 ng/mL for recombinant p27 and 12.5 × 10(4) IU/mL for FeLV. When evaluating 252 cat sera samples, the kit was found to have a kappa value of 0.88 compared to polymerase chain reaction (PCR), indicating a significant correlation between data from the rapid diagnostic test and PCR. Sensitivity and specificity of the kit were 95.2% (20/21) and 98.5% (257/261), respectively. Our results demonstrated that the rapid diagnostic test would be a suitable diagnostic tool for the rapid detection of FeLV infection in cats.",2014 Mar 19,"['Kim, Won-Shik', 'Chong, Chom-Kyu', 'Kim, Hak-Yong', 'Lee, Gyu-Cheol', 'Jeong, Wooseog', 'An, Dong-Jun', 'Jeoung, Hye-Young', 'Lee, Jae-In', 'Lee, Young-Ki']",J Vet Sci,,,True
789ca66c03e2a2aaf30da4cf0df1d25b6b37b9d5,PMC,Investments in respiratory infectious disease research 1997–2010: a systematic analysis of UK funding,http://dx.doi.org/10.1136/bmjopen-2013-004600,PMC3975787,24670431,CC BY-NC,"OBJECTIVES: Respiratory infections are responsible for a large global burden of disease. We assessed the public and philanthropic investments awarded to UK institutions for respiratory infectious disease research to identify areas of underinvestment. We aimed to identify projects and categorise them by pathogen, disease and position along the research and development value chain. SETTING: The UK. PARTICIPANTS: Institutions that host and carry out infectious disease research. PRIMARY AND SECONDARY OUTCOME MEASURES: The total amount spent and number of studies with a focus on several different respiratory pathogens or diseases, and to correlate these against the global burden of disease; also the total amount spent and number of studies relating to the type of science, the predominant funder in each category and the mean and median award size. RESULTS: We identified 6165 infectious disease studies with a total investment of £2·6 billion. Respiratory research received £419 million (16.1%) across 1192 (19.3%) studies. The Wellcome Trust provided greatest investment (£135.2 million; 32.3%). Tuberculosis received £155 million (37.1%), influenza £80 million (19.1%) and pneumonia £27.8 million (6.6%). Despite high burden, there was relatively little investment in vaccine-preventable diseases including diphtheria (£0.1 million, 0.03%), measles (£5.0 million, 1.2%) and drug-resistant tuberculosis. There were 802 preclinical studies (67.3%) receiving £273 million (65.2%), while implementation research received £81 million (19.3%) across 274 studies (23%). There were comparatively few phase I–IV trials or product development studies. Global health research received £68.3 million (16.3%). Relative investment was strongly correlated with 2010 disease burden. CONCLUSIONS: The UK predominantly funds preclinical science. Tuberculosis is the most studied respiratory disease. The high global burden of pneumonia-related disease warrants greater investment than it has historically received. Other priority areas include antimicrobial resistance (particularly within tuberculosis), economics and proactive investments for emerging infectious threats.",2014 Mar 26,"['Head, Michael G', 'Fitchett, Joseph R', 'Cooke, Mary K', 'Wurie, Fatima B', 'Hayward, Andrew C', 'Lipman, Marc C', 'Atun, Rifat']",BMJ Open,,,True
9449746a1b41b08251ce0e1cb8fc5654b2faf043,PMC,Investments in respiratory infectious disease research 1997–2010: a systematic analysis of UK funding,http://dx.doi.org/10.1136/bmjopen-2013-004600,PMC3975787,24670431,CC BY-NC,"OBJECTIVES: Respiratory infections are responsible for a large global burden of disease. We assessed the public and philanthropic investments awarded to UK institutions for respiratory infectious disease research to identify areas of underinvestment. We aimed to identify projects and categorise them by pathogen, disease and position along the research and development value chain. SETTING: The UK. PARTICIPANTS: Institutions that host and carry out infectious disease research. PRIMARY AND SECONDARY OUTCOME MEASURES: The total amount spent and number of studies with a focus on several different respiratory pathogens or diseases, and to correlate these against the global burden of disease; also the total amount spent and number of studies relating to the type of science, the predominant funder in each category and the mean and median award size. RESULTS: We identified 6165 infectious disease studies with a total investment of £2·6 billion. Respiratory research received £419 million (16.1%) across 1192 (19.3%) studies. The Wellcome Trust provided greatest investment (£135.2 million; 32.3%). Tuberculosis received £155 million (37.1%), influenza £80 million (19.1%) and pneumonia £27.8 million (6.6%). Despite high burden, there was relatively little investment in vaccine-preventable diseases including diphtheria (£0.1 million, 0.03%), measles (£5.0 million, 1.2%) and drug-resistant tuberculosis. There were 802 preclinical studies (67.3%) receiving £273 million (65.2%), while implementation research received £81 million (19.3%) across 274 studies (23%). There were comparatively few phase I–IV trials or product development studies. Global health research received £68.3 million (16.3%). Relative investment was strongly correlated with 2010 disease burden. CONCLUSIONS: The UK predominantly funds preclinical science. Tuberculosis is the most studied respiratory disease. The high global burden of pneumonia-related disease warrants greater investment than it has historically received. Other priority areas include antimicrobial resistance (particularly within tuberculosis), economics and proactive investments for emerging infectious threats.",2014 Mar 26,"['Head, Michael G', 'Fitchett, Joseph R', 'Cooke, Mary K', 'Wurie, Fatima B', 'Hayward, Andrew C', 'Lipman, Marc C', 'Atun, Rifat']",BMJ Open,,,True
5c81cdd41052486b6cced1934b0f959e4361f975,PMC,Investments in respiratory infectious disease research 1997–2010: a systematic analysis of UK funding,http://dx.doi.org/10.1136/bmjopen-2013-004600,PMC3975787,24670431,CC BY-NC,"OBJECTIVES: Respiratory infections are responsible for a large global burden of disease. We assessed the public and philanthropic investments awarded to UK institutions for respiratory infectious disease research to identify areas of underinvestment. We aimed to identify projects and categorise them by pathogen, disease and position along the research and development value chain. SETTING: The UK. PARTICIPANTS: Institutions that host and carry out infectious disease research. PRIMARY AND SECONDARY OUTCOME MEASURES: The total amount spent and number of studies with a focus on several different respiratory pathogens or diseases, and to correlate these against the global burden of disease; also the total amount spent and number of studies relating to the type of science, the predominant funder in each category and the mean and median award size. RESULTS: We identified 6165 infectious disease studies with a total investment of £2·6 billion. Respiratory research received £419 million (16.1%) across 1192 (19.3%) studies. The Wellcome Trust provided greatest investment (£135.2 million; 32.3%). Tuberculosis received £155 million (37.1%), influenza £80 million (19.1%) and pneumonia £27.8 million (6.6%). Despite high burden, there was relatively little investment in vaccine-preventable diseases including diphtheria (£0.1 million, 0.03%), measles (£5.0 million, 1.2%) and drug-resistant tuberculosis. There were 802 preclinical studies (67.3%) receiving £273 million (65.2%), while implementation research received £81 million (19.3%) across 274 studies (23%). There were comparatively few phase I–IV trials or product development studies. Global health research received £68.3 million (16.3%). Relative investment was strongly correlated with 2010 disease burden. CONCLUSIONS: The UK predominantly funds preclinical science. Tuberculosis is the most studied respiratory disease. The high global burden of pneumonia-related disease warrants greater investment than it has historically received. Other priority areas include antimicrobial resistance (particularly within tuberculosis), economics and proactive investments for emerging infectious threats.",2014 Mar 26,"['Head, Michael G', 'Fitchett, Joseph R', 'Cooke, Mary K', 'Wurie, Fatima B', 'Hayward, Andrew C', 'Lipman, Marc C', 'Atun, Rifat']",BMJ Open,,,False
0e2c97d34c8c6042f26cc11e83e1a2fbac521203,PMC,A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant,http://dx.doi.org/10.1128/mBio.00047-14,PMC3977350,24667706,CC BY-NC-SA,"Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and Pipistrellus bat coronavirus (BtCoV) strain HKU5 of Betacoronavirus (β-CoV) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine targets. BtCoV HKU5 has been described in silico but has not been shown to replicate in culture, thus hampering drug and vaccine studies against subgroup 2c β-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5 containing the severe acute respiratory syndrome (SARS)-CoV spike (S) glycoprotein ectodomain (BtCoV HKU5-SE). This virus replicates efficiently in cell culture and in young and aged mice, where the virus targets airway and alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence, causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14, open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs. Synthetic-genome platforms capable of reconstituting emerging zoonotic viral pathogens or their phylogenetic relatives provide new strategies for identifying broad-based therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis.",2014 Mar 25,"['Agnihothram, Sudhakar', 'Yount, Boyd L.', 'Donaldson, Eric F.', 'Huynh, Jeremy', 'Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Graham, Rachel L.', 'Becker, Michelle M.', 'Tomar, Sakshi', 'Scobey, Trevor D.', 'Osswald, Heather L.', 'Whitmore, Alan', 'Gopal, Robin', 'Ghosh, Arun K.', 'Mesecar, Andrew', 'Zambon, Maria', 'Heise, Mark', 'Denison, Mark R.', 'Baric, Ralph S.']",mBio,,,True
6d7409f2c817cb5020e69c9dfe160d04a355cf5e,PMC,A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant,http://dx.doi.org/10.1128/mBio.00047-14,PMC3977350,24667706,CC BY-NC-SA,"Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and Pipistrellus bat coronavirus (BtCoV) strain HKU5 of Betacoronavirus (β-CoV) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine targets. BtCoV HKU5 has been described in silico but has not been shown to replicate in culture, thus hampering drug and vaccine studies against subgroup 2c β-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5 containing the severe acute respiratory syndrome (SARS)-CoV spike (S) glycoprotein ectodomain (BtCoV HKU5-SE). This virus replicates efficiently in cell culture and in young and aged mice, where the virus targets airway and alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence, causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14, open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs. Synthetic-genome platforms capable of reconstituting emerging zoonotic viral pathogens or their phylogenetic relatives provide new strategies for identifying broad-based therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis.",2014 Mar 25,"['Agnihothram, Sudhakar', 'Yount, Boyd L.', 'Donaldson, Eric F.', 'Huynh, Jeremy', 'Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Graham, Rachel L.', 'Becker, Michelle M.', 'Tomar, Sakshi', 'Scobey, Trevor D.', 'Osswald, Heather L.', 'Whitmore, Alan', 'Gopal, Robin', 'Ghosh, Arun K.', 'Mesecar, Andrew', 'Zambon, Maria', 'Heise, Mark', 'Denison, Mark R.', 'Baric, Ralph S.']",mBio,,,False
80be90e5d6b0738a8fd58c5fe915da7072f7f13f,PMC,A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant,http://dx.doi.org/10.1128/mBio.00047-14,PMC3977350,24667706,CC BY-NC-SA,"Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and Pipistrellus bat coronavirus (BtCoV) strain HKU5 of Betacoronavirus (β-CoV) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine targets. BtCoV HKU5 has been described in silico but has not been shown to replicate in culture, thus hampering drug and vaccine studies against subgroup 2c β-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5 containing the severe acute respiratory syndrome (SARS)-CoV spike (S) glycoprotein ectodomain (BtCoV HKU5-SE). This virus replicates efficiently in cell culture and in young and aged mice, where the virus targets airway and alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence, causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14, open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs. Synthetic-genome platforms capable of reconstituting emerging zoonotic viral pathogens or their phylogenetic relatives provide new strategies for identifying broad-based therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis.",2014 Mar 25,"['Agnihothram, Sudhakar', 'Yount, Boyd L.', 'Donaldson, Eric F.', 'Huynh, Jeremy', 'Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Graham, Rachel L.', 'Becker, Michelle M.', 'Tomar, Sakshi', 'Scobey, Trevor D.', 'Osswald, Heather L.', 'Whitmore, Alan', 'Gopal, Robin', 'Ghosh, Arun K.', 'Mesecar, Andrew', 'Zambon, Maria', 'Heise, Mark', 'Denison, Mark R.', 'Baric, Ralph S.']",mBio,,,False
ffb049554e1813b3504412b7ab69bc636697c0c6,PMC,A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant,http://dx.doi.org/10.1128/mBio.00047-14,PMC3977350,24667706,CC BY-NC-SA,"Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and Pipistrellus bat coronavirus (BtCoV) strain HKU5 of Betacoronavirus (β-CoV) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine targets. BtCoV HKU5 has been described in silico but has not been shown to replicate in culture, thus hampering drug and vaccine studies against subgroup 2c β-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5 containing the severe acute respiratory syndrome (SARS)-CoV spike (S) glycoprotein ectodomain (BtCoV HKU5-SE). This virus replicates efficiently in cell culture and in young and aged mice, where the virus targets airway and alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence, causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14, open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs. Synthetic-genome platforms capable of reconstituting emerging zoonotic viral pathogens or their phylogenetic relatives provide new strategies for identifying broad-based therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis.",2014 Mar 25,"['Agnihothram, Sudhakar', 'Yount, Boyd L.', 'Donaldson, Eric F.', 'Huynh, Jeremy', 'Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Graham, Rachel L.', 'Becker, Michelle M.', 'Tomar, Sakshi', 'Scobey, Trevor D.', 'Osswald, Heather L.', 'Whitmore, Alan', 'Gopal, Robin', 'Ghosh, Arun K.', 'Mesecar, Andrew', 'Zambon, Maria', 'Heise, Mark', 'Denison, Mark R.', 'Baric, Ralph S.']",mBio,,,False
475aee21f8e242fcf970bf070e9ff00c69117b37,PMC,A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant,http://dx.doi.org/10.1128/mBio.00047-14,PMC3977350,24667706,CC BY-NC-SA,"Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and Pipistrellus bat coronavirus (BtCoV) strain HKU5 of Betacoronavirus (β-CoV) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine targets. BtCoV HKU5 has been described in silico but has not been shown to replicate in culture, thus hampering drug and vaccine studies against subgroup 2c β-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5 containing the severe acute respiratory syndrome (SARS)-CoV spike (S) glycoprotein ectodomain (BtCoV HKU5-SE). This virus replicates efficiently in cell culture and in young and aged mice, where the virus targets airway and alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence, causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14, open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs. Synthetic-genome platforms capable of reconstituting emerging zoonotic viral pathogens or their phylogenetic relatives provide new strategies for identifying broad-based therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis.",2014 Mar 25,"['Agnihothram, Sudhakar', 'Yount, Boyd L.', 'Donaldson, Eric F.', 'Huynh, Jeremy', 'Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Graham, Rachel L.', 'Becker, Michelle M.', 'Tomar, Sakshi', 'Scobey, Trevor D.', 'Osswald, Heather L.', 'Whitmore, Alan', 'Gopal, Robin', 'Ghosh, Arun K.', 'Mesecar, Andrew', 'Zambon, Maria', 'Heise, Mark', 'Denison, Mark R.', 'Baric, Ralph S.']",mBio,,,False
e11909aafacbf794c1ace5077ef97e9e28ef34f9,PMC,A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant,http://dx.doi.org/10.1128/mBio.00047-14,PMC3977350,24667706,CC BY-NC-SA,"Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and Pipistrellus bat coronavirus (BtCoV) strain HKU5 of Betacoronavirus (β-CoV) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine targets. BtCoV HKU5 has been described in silico but has not been shown to replicate in culture, thus hampering drug and vaccine studies against subgroup 2c β-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5 containing the severe acute respiratory syndrome (SARS)-CoV spike (S) glycoprotein ectodomain (BtCoV HKU5-SE). This virus replicates efficiently in cell culture and in young and aged mice, where the virus targets airway and alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence, causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14, open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs. Synthetic-genome platforms capable of reconstituting emerging zoonotic viral pathogens or their phylogenetic relatives provide new strategies for identifying broad-based therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis.",2014 Mar 25,"['Agnihothram, Sudhakar', 'Yount, Boyd L.', 'Donaldson, Eric F.', 'Huynh, Jeremy', 'Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Graham, Rachel L.', 'Becker, Michelle M.', 'Tomar, Sakshi', 'Scobey, Trevor D.', 'Osswald, Heather L.', 'Whitmore, Alan', 'Gopal, Robin', 'Ghosh, Arun K.', 'Mesecar, Andrew', 'Zambon, Maria', 'Heise, Mark', 'Denison, Mark R.', 'Baric, Ralph S.']",mBio,,,False
37659e5b68f171f2d4f33f15d143031060b673ec,PMC,A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant,http://dx.doi.org/10.1128/mBio.00047-14,PMC3977350,24667706,CC BY-NC-SA,"Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and Pipistrellus bat coronavirus (BtCoV) strain HKU5 of Betacoronavirus (β-CoV) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine targets. BtCoV HKU5 has been described in silico but has not been shown to replicate in culture, thus hampering drug and vaccine studies against subgroup 2c β-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5 containing the severe acute respiratory syndrome (SARS)-CoV spike (S) glycoprotein ectodomain (BtCoV HKU5-SE). This virus replicates efficiently in cell culture and in young and aged mice, where the virus targets airway and alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence, causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14, open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs. Synthetic-genome platforms capable of reconstituting emerging zoonotic viral pathogens or their phylogenetic relatives provide new strategies for identifying broad-based therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis.",2014 Mar 25,"['Agnihothram, Sudhakar', 'Yount, Boyd L.', 'Donaldson, Eric F.', 'Huynh, Jeremy', 'Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Graham, Rachel L.', 'Becker, Michelle M.', 'Tomar, Sakshi', 'Scobey, Trevor D.', 'Osswald, Heather L.', 'Whitmore, Alan', 'Gopal, Robin', 'Ghosh, Arun K.', 'Mesecar, Andrew', 'Zambon, Maria', 'Heise, Mark', 'Denison, Mark R.', 'Baric, Ralph S.']",mBio,,,False
ebf82d3f85bc581e3e2276ae6e8b133228515e83,PMC,Middle East Respiratory Syndrome Coronavirus Infection in Dromedary Camels in Saudi Arabia,http://dx.doi.org/10.1128/mBio.01002-14,PMC3977356,,CC BY-NC-SA,,2014 Mar 25,"['Alagaili, Abdulaziz N.', 'Briese, Thomas', 'Mishra, Nischay', 'Kapoor, Vishal', 'Sameroff, Stephen C.', 'Burbelo, Peter D.', 'de Wit, Emmie', 'Munster, Vincent J.', 'Hensley, Lisa E.', 'Zalmout, Iyad S.', 'Kapoor, Amit', 'Epstein, Jonathan H.', 'Karesh, William B.', 'Daszak, Peter', 'Mohammed, Osama B.', 'Lipkin, W. Ian']",mBio,,,False
c2eb9541f460ced6480edf97d9b89f8e838dc01e,PMC,Is Virology Dead?,http://dx.doi.org/10.1128/mBio.01003-14,PMC3977357,24667711,CC BY-NC-SA,,2014 Mar 25,"DiMaio, Daniel",mBio,,,True
ec66e69291414e8f29b5db27eecbc8e9cdcf2c20,PMC,Competitive Fitness in Coronaviruses Is Not Correlated with Size or Number of Double-Membrane Vesicles under Reduced-Temperature Growth Conditions,http://dx.doi.org/10.1128/mBio.01107-13,PMC3977362,24692638,CC BY-NC-SA,"Positive-stranded viruses synthesize their RNA in membrane-bound organelles, but it is not clear how this benefits the virus or the host. For coronaviruses, these organelles take the form of double-membrane vesicles (DMVs) interconnected by a convoluted membrane network. We used electron microscopy to identify murine coronaviruses with mutations in nsp3 and nsp14 that replicated normally while producing only half the normal amount of DMVs under low-temperature growth conditions. Viruses with mutations in nsp5 and nsp16 produced small DMVs but also replicated normally. Quantitative reverse transcriptase PCR (RT-PCR) confirmed that the most strongly affected of these, the nsp3 mutant, produced more viral RNA than wild-type virus. Competitive growth assays were carried out in both continuous and primary cells to better understand the contribution of DMVs to viral fitness. Surprisingly, several viruses that produced fewer or smaller DMVs showed a higher fitness than wild-type virus at the reduced temperature, suggesting that larger and more numerous DMVs do not necessarily confer a competitive advantage in primary or continuous cell culture. For the first time, this directly demonstrates that replication and organelle formation may be, at least in part, studied separately during infection with positive-stranded RNA virus.",2014 Apr 1,"['Al-Mulla, Hawaa M. N.', 'Turrell, Lauren', 'Smith, Nicola M.', 'Payne, Luke', 'Baliji, Surendranath', 'Züst, Roland', 'Thiel, Volker', 'Baker, Susan C.', 'Siddell, Stuart G.', 'Neuman, Benjamin W.']",mBio,,,True
9adb9a55bc7756ff69f23f66796941b73f40f4a1,PMC,Modulation of HIV-1 immunity by adjuvants,http://dx.doi.org/10.1097/COH.0000000000000052,PMC3984023,24670321,CC BY-NC-ND,"PURPOSE OF REVIEW: To summarize the role of adjuvants in eliciting desirable antibody responses against HIV-1 with particular emphasis on both historical context and recent developments. RECENT FINDINGS: Increased understanding of the role of pattern recognition receptors such as Toll-like receptors in recruiting and directing the immune system has increased the variety of adjuvant formulations being tested in animal models and humans. Across all vaccine platforms, adjuvant formulations have been shown to enhance desirable immune responses such as higher antibody titers and increased functional activity. Although no vaccine formulation has yet succeeded in eliciting broad neutralizing antibodies against HIV-1, the ability of adjuvants to direct the immune response to immunogens suggests they will be critically important in any successful HIV-1 vaccine. SUMMARY: The parallel development of adjuvants along with better HIV-1 immunogens will be needed for a successful AIDS vaccine. Additional comparative testing will be required to determine the optimal adjuvant and immunogen regimen that can elicit antibody responses capable of blocking HIV-1 transmission.",2014 May 10,"Moody, M. Anthony",Curr Opin HIV AIDS,,,True
afb768d18ca2b01aacb890d056487c1a00681e72,PMC,Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations,http://dx.doi.org/10.1136/bmjopen-2013-004699,PMC3987727,24710133,CC BY-NC,"INTRODUCTION: Oral corticosteroids are the cornerstone of acute asthma management in the emergency department. Recent evidence has raised doubts about the efficacy of this treatment in preschool-aged children with viral-induced wheezing and in smoking adults. The aims of the study were to: (1) document the magnitude of response to oral corticosteroids in children presenting to the emergency department with moderate or severe asthma; (2) quantify potential determinants of response to corticosteroids and (3) explore the role of gene polymorphisms associated with the responsiveness to corticosteroids. METHODS AND ANALYSIS: The design is a prospective cohort study of 1008 children aged 1–17 years meeting a strict definition of asthma and presenting with a clinical score of ≥4 on the validated Pediatric Respiratory Assessment Measure. All children will receive standardised severity-specific treatment with prednisone/prednisolone and cointerventions (salbutamol with/without ipratropium bromide). Determinants, namely viral aetiology, environmental tobacco smoke and single nucleotide polymorphism, will be objectively documented. The primary efficacy endpoint is the failure of emergency department (ED) management within 72 h of the ED visit. Secondary endpoints include other measures of asthma severity and time to recovery within 7 days of the index visit. The study has 80% power for detecting a risk difference of 7.5% associated with each determinant from a baseline risk of 21%, at an α of 0.05. ETHICS AND DISSEMINATION: Ethical approval has been obtained from all participating institutions. An impaired response to systemic steroids in certain subgroups will challenge the current standard of practice and call for the immediate search for better approaches. A potential host–environment interaction will broaden our understanding of corticosteroid responsiveness in children. Documentation of similar effectiveness of corticosteroids across determinants will provide the needed reassurance regarding current treatment recommendations. RESULTS: Results will be disseminated at international conferences and manuscripts targeted at emergency physicians, paediatricians, geneticists and respirologists. TRIAL REGISTRATION NUMBER: This study is registered at Clinicaltrials.gov (NCT02013076).",2014 Apr 5,"['Ducharme, F M', 'Zemek, R', 'Gravel, J', 'Chalut, D', 'Poonai, N', 'Laberge, S', 'Quach, C', 'Krajinovic, M', 'Guimont, C', 'Lemière, C', 'Guertin, M C']",BMJ Open,,,True
08f6c419a42b6c922108349af6c1b2aaf2cc62b2,PMC,Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations,http://dx.doi.org/10.1136/bmjopen-2013-004699,PMC3987727,24710133,CC BY-NC,"INTRODUCTION: Oral corticosteroids are the cornerstone of acute asthma management in the emergency department. Recent evidence has raised doubts about the efficacy of this treatment in preschool-aged children with viral-induced wheezing and in smoking adults. The aims of the study were to: (1) document the magnitude of response to oral corticosteroids in children presenting to the emergency department with moderate or severe asthma; (2) quantify potential determinants of response to corticosteroids and (3) explore the role of gene polymorphisms associated with the responsiveness to corticosteroids. METHODS AND ANALYSIS: The design is a prospective cohort study of 1008 children aged 1–17 years meeting a strict definition of asthma and presenting with a clinical score of ≥4 on the validated Pediatric Respiratory Assessment Measure. All children will receive standardised severity-specific treatment with prednisone/prednisolone and cointerventions (salbutamol with/without ipratropium bromide). Determinants, namely viral aetiology, environmental tobacco smoke and single nucleotide polymorphism, will be objectively documented. The primary efficacy endpoint is the failure of emergency department (ED) management within 72 h of the ED visit. Secondary endpoints include other measures of asthma severity and time to recovery within 7 days of the index visit. The study has 80% power for detecting a risk difference of 7.5% associated with each determinant from a baseline risk of 21%, at an α of 0.05. ETHICS AND DISSEMINATION: Ethical approval has been obtained from all participating institutions. An impaired response to systemic steroids in certain subgroups will challenge the current standard of practice and call for the immediate search for better approaches. A potential host–environment interaction will broaden our understanding of corticosteroid responsiveness in children. Documentation of similar effectiveness of corticosteroids across determinants will provide the needed reassurance regarding current treatment recommendations. RESULTS: Results will be disseminated at international conferences and manuscripts targeted at emergency physicians, paediatricians, geneticists and respirologists. TRIAL REGISTRATION NUMBER: This study is registered at Clinicaltrials.gov (NCT02013076).",2014 Apr 5,"['Ducharme, F M', 'Zemek, R', 'Gravel, J', 'Chalut, D', 'Poonai, N', 'Laberge, S', 'Quach, C', 'Krajinovic, M', 'Guimont, C', 'Lemière, C', 'Guertin, M C']",BMJ Open,,,True
722738d238370488034852a1867cfa04b564d331,PMC,Evaluation of an Immunochromatographic Assay for the Rapid and Simultaneous Detection of Rotavirus and Adenovirus in Stool Samples,http://dx.doi.org/10.3343/alm.2014.34.3.216,PMC3999320,24790909,CC BY-NC,"BACKGROUND: We evaluated the analytical and clinical performances of the SD BIOLINE Rota/Adeno Rapid kit (SD Rota/Adeno Rapid; Standard Diagnostics, Inc., Korea), an immunochromatographic assay (ICA), for the simultaneous detection of rotaviruses and adenoviruses in human stool samples. METHODS: We tested 400 clinical stool samples from patients with acute gastroenteritis and compared the ICA results with the results obtained by using ELISA, enzyme-linked fluorescent assays (ELFA), PCR, and multiplex reverse transcription-PCR (mRT-PCR). To assess the analytical performance of the SD BIOLINE Rota/Adeno Rapid kit, we determined its detection limit, reproducibility, cross-reactivity, and analytical reactivity for adenovirus subtypes, and performed interference studies. RESULTS: The overall agreement rates among the tested methods were 91.5% for rotavirus and 85.5% for adenovirus. On the basis of mRT-PCR, the overall agreement, positive agreement, and negative agreement rates of the ICA were 95.6%, 100%, and 94.9% for rotavirus, and 94.0%, 71.4%, and 94.8% for adenovirus, respectively. Using the ICA, we detected all the subtypes of adenovirus tested, but the analytical reactivities for adenovirus subtypes were different between the 4 adenovirus detection methods. The high reproducibility was confirmed, and no cross-reactivity or interference was detected. CONCLUSIONS: The SD BIOLINE Rota/Adeno Rapid kit showed acceptable analytical and clinical performances. However, interpretation of adenovirus positive/negative result should be cautious because of different detectability for adenovirus subtypes among adenovirus detection methods.",2014 May 8,"['Kim, Jayoung', 'Kim, Hyun Soo', 'Kim, Han-Sung', 'Kim, Jae-Seok', 'Song, Wonkeun', 'Lee, Kyu Man', 'Lee, Sunhwa', 'Park, Kyoung Un', 'Lee, Woochang', 'Hong, Young Jun']",Ann Lab Med,,,True
241348149ec43ddce1d3033145b00307db56aea0,PMC,Tanshinone IIA Attenuates Bleomycin-Induced Pulmonary Fibrosis via Modulating Angiotensin-Converting Enzyme 2/ Angiotensin-(1-7) Axis in Rats,http://dx.doi.org/10.7150/ijms.8365,PMC4003542,24782646,CC BY-NC-ND,"Pulmonary fibrosis (PF) is a common complication in those interstitial lung diseases patients, which will result in poor prognosis and short survival. Traditional therapeutic methods such as glucocorticoid and cytotoxic drugs are insufficient for treating PF and may cause severe side effects. Recent studies showed that traditional Chinese herbal abstraction such as Tanshinone IIA (TIIA) was displayed significant anti-PF effects in animal models. However, the exact mechanisms underlying the protective effects of TIIA were not fully understood. Here we further investigated the protective effects of TIIA and its mechanisms underlying. PF models of rat were induced by bleomycin (BLM); TIIA was administered subsequently. The PF changes were identified by histopathological analyses. The results showed that BLM resulted in severe PF and alveolar inflammation; together with significant elevation of transforming growth factor-β 1 (TGF-β1). Angiotensin-converting enzyme 2 (ACE-2) together with angiotensin-(1-7) [ANG-(1-7)] were both greatly reduced after BLM administration. TIIA treatment notably attenuated BLM induced PF and inflammation, decreased expression of TGF-β1 and reversed ACE-2 and ANG-(1-7) production in rat lungs. Thus we may draw the conclusion that TIIA may exert protective effects on BLM induced PF in rats, and the ACE-2/ANG-(1-7) axis may ascribe to those protective effects.",2014 Apr 7,"['Wu, Huajie', 'Li, Yan', 'Wang, Yanxia', 'Xu, Dunquan', 'Li, Congcong', 'Liu, Manling', 'Sun, Xin', 'Li, Zhichao']",Int J Med Sci,,,True
5e4eac58c90d3c48ae4f87bb76dcff9520dde6b0,PMC,The Ups and Downs of Emerging Infectious Diseases at Your Fingertips,http://dx.doi.org/10.1128/jmbe.v15i1.707,PMC4004752,,CC BY-NC-SA,,2014 May 1,"Jandu, Narveen",J Microbiol Biol Educ,,,False
29484085aa4df22fec44839b58dcdce03f1c3e82,PMC,Construction and characterisation of a complete reverse genetics system of dengue virus type 3,http://dx.doi.org/10.1590/0074-0276130298,PMC4005542,24402142,CC BY-NC,"Dengue virulence and fitness are important factors that determine disease outcome. However, dengue virus (DENV) molecular biology and pathogenesis are not completely elucidated. New insights on those mechanisms have been facilitated by the development of reverse genetic systems in the past decades. Unfortunately, instability of flavivirus genomes cloned in Escherichia coli has been a major problem in these systems. Here, we describe the development of a complete reverse genetics system, based on the construction of an infectious clone and replicon for a low passage DENV-3 genotype III of a clinical isolate. Both constructs were assembled into a newly designed yeast- E. coli shuttle vector by homologous recombination technique and propagated in yeast to prevent any possible genome instability in E. coli . RNA transcripts derived from the infectious clone are infectious upon transfection into BHK-21 cells even after repeated passages of the plasmid in yeast. Transcript-derived DENV-3 exhibited growth kinetics, focus formation size comparable to original DENV-3 in mosquito C6/36 cell culture. In vitro characterisation of DENV-3 replicon confirmed its identity and ability to replicate transiently in BHK-21 cells. The reverse genetics system reported here is a valuable tool that will facilitate further molecular studies in DENV replication, virus attenuation and pathogenesis.",2013 Dec 11,"['Santos, Jefferson José da Silva', 'Cordeiro, Marli Tenório', 'Bertani, Giovani Rota', 'Marques, Ernesto Torres de Azevedo', 'Gil, Laura Helena Vega Gonzales']",Mem Inst Oswaldo Cruz,,,True
280c43e8272c97d38089e567dbf1881430e60dd9,PMC,Addition of poly (propylene glycol) to multiblock copolymer to optimize siRNA delivery,http://dx.doi.org/10.4161/bioe.27339,PMC4008463,24424156,CC BY-NC,"Previous studies have examined different strategies for siRNA delivery with varying degrees of success. These include use of viral vectors, cationic liposomes, and polymers. Several copolymers were designed and synthesized based on blocks of poly(ethylene glycol) PEG, poly(propylene glycol) PPG, and poly(l-lysine). These were designated as P1, P2, and P3. We studied the copolymer self-assembly, siRNA binding, particle size, surface potential, architecture of the complexes, and siRNA delivery. Silencing of GFP using copolymer P3 to deliver GFP-specific siRNA to Neuro-2a cells expressing GFP was almost as effective as using Lipofectamine 2000, with minimal cytotoxicity. Thus, we have provided a new copolymer platform for siRNA delivery that we can continue to modify for improved delivery of siRNA in vitro and eventually in vivo.",2014 Jan 1,"['Dai, Zhi', 'Arévalo, Maria T', 'Li, Junwei', 'Zeng, Mingtao']",Bioengineered,,,True
d0c4236f95ba2b3d5cdc71fde524b26262f05dd3,PMC,A Brief Review: The Z-curve Theory and its Application in Genome Analysis,http://dx.doi.org/10.2174/1389202915999140328162433,PMC4009844,24822026,CC BY-NC,"In theoretical physics, there exist two basic mathematical approaches, algebraic and geometrical methods, which, in most cases, are complementary. In the area of genome sequence analysis, however, algebraic approaches have been widely used, while geometrical approaches have been less explored for a long time. The Z-curve theory is a geometrical approach to genome analysis. The Z-curve is a three-dimensional curve that represents a given DNA sequence in the sense that each can be uniquely reconstructed given the other. The Z-curve, therefore, contains all the information that the corresponding DNA sequence carries. The analysis of a DNA sequence can then be performed through studying the corresponding Z-curve. The Z-curve method has found applications in a wide range of areas in the past two decades, including the identifications of protein-coding genes, replication origins, horizontally-transferred genomic islands, promoters, translational start sides and isochores, as well as studies on phylogenetics, genome visualization and comparative genomics. Here, we review the progress of Z-curve studies from aspects of both theory and applications in genome analysis.",2014 Apr,"['Zhang, Ren', 'Zhang, Chun-Ting']",Curr Genomics,,,True
bddfc27eab5ed01ee09fcab0f11fd6c0a0bd458e,PMC,Middle East Respiratory Syndrome Coronavirus Quasispecies That Include Homologues of Human Isolates Revealed through Whole-Genome Analysis and Virus Cultured from Dromedary Camels in Saudi Arabia,http://dx.doi.org/10.1128/mBio.01146-14,PMC4010836,24781747,CC BY-NC-SA,"Complete Middle East respiratory syndrome coronavirus (MERS-CoV) genome sequences were obtained from nasal swabs of dromedary camels sampled in the Kingdom of Saudi Arabia through direct analysis of nucleic acid extracts or following virus isolation in cell culture. Consensus dromedary MERS-CoV genome sequences were the same with either template source and identical to published human MERS-CoV sequences. However, in contrast to individual human cases, where only clonal genomic sequences are reported, detailed population analyses revealed the presence of more than one genomic variant in individual dromedaries. If humans are truly infected only with clonal virus populations, we must entertain a model for interspecies transmission of MERS-CoV wherein only specific genotypes are capable of passing bottleneck selection.",2014 Apr 29,"['Briese, Thomas', 'Mishra, Nischay', 'Jain, Komal', 'Zalmout, Iyad S.', 'Jabado, Omar J.', 'Karesh, William B.', 'Daszak, Peter', 'Mohammed, Osama B.', 'Alagaili, Abdulaziz N.', 'Lipkin, W. Ian']",mBio,,,True
efba89b391778e0a50fd18b5a57dcc5b7d7ab4ee,PMC,Middle East Respiratory Syndrome Coronavirus Quasispecies That Include Homologues of Human Isolates Revealed through Whole-Genome Analysis and Virus Cultured from Dromedary Camels in Saudi Arabia,http://dx.doi.org/10.1128/mBio.01146-14,PMC4010836,24781747,CC BY-NC-SA,"Complete Middle East respiratory syndrome coronavirus (MERS-CoV) genome sequences were obtained from nasal swabs of dromedary camels sampled in the Kingdom of Saudi Arabia through direct analysis of nucleic acid extracts or following virus isolation in cell culture. Consensus dromedary MERS-CoV genome sequences were the same with either template source and identical to published human MERS-CoV sequences. However, in contrast to individual human cases, where only clonal genomic sequences are reported, detailed population analyses revealed the presence of more than one genomic variant in individual dromedaries. If humans are truly infected only with clonal virus populations, we must entertain a model for interspecies transmission of MERS-CoV wherein only specific genotypes are capable of passing bottleneck selection.",2014 Apr 29,"['Briese, Thomas', 'Mishra, Nischay', 'Jain, Komal', 'Zalmout, Iyad S.', 'Jabado, Omar J.', 'Karesh, William B.', 'Daszak, Peter', 'Mohammed, Osama B.', 'Alagaili, Abdulaziz N.', 'Lipkin, W. Ian']",mBio,,,False
92142e072745fbab996c5861e5974aa03805398a,PMC,The Role of Macrophage Polarization in Infectious and Inflammatory Diseases,http://dx.doi.org/10.14348/molcells.2014.2374,PMC4012075,24625576,CC BY-NC-SA,"Macrophages, found in circulating blood as well as integrated into several tissues and organs throughout the body, represent an important first line of defense against disease and a necessary component of healthy tissue homeostasis. Additionally, macrophages that arise from the differentiation of monocytes recruited from the blood to inflamed tissues play a central role in regulating local inflammation. Studies of macrophage activation in the last decade or so have revealed that these cells adopt a staggering range of phenotypes that are finely tuned responses to a variety of different stimuli, and that the resulting subsets of activated macrophages play critical roles in both progression and resolution of disease. This review summarizes the current understanding of the contributions of differentially polarized macrophages to various infectious and inflammatory diseases and the ongoing effort to develop novel therapies that target this key aspect of macrophage biology.",2014 Apr 30,"['Labonte, Adam C.', 'Tosello-Trampont, Annie-Carole', 'Hahn, Young S.']",Mol Cells,,,True
fef0bb9eaac69559d0ff2f92ff83e0affd4435f0,PMC,Pathogenic Influenza Viruses and Coronaviruses Utilize Similar and Contrasting Approaches To Control Interferon-Stimulated Gene Responses,http://dx.doi.org/10.1128/mBio.01174-14,PMC4030454,24846384,CC BY-NC-SA,"The broad range and diversity of interferon-stimulated genes (ISGs) function to induce an antiviral state within the host, impeding viral pathogenesis. While successful respiratory viruses overcome individual ISG effectors, analysis of the global ISG response and subsequent viral antagonism has yet to be examined. Employing models of the human airway, transcriptomics and proteomics datasets were used to compare ISG response patterns following highly pathogenic H5N1 avian influenza (HPAI) A virus, 2009 pandemic H1N1, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome CoV (MERS-CoV) infection. The results illustrated distinct approaches utilized by each virus to antagonize the global ISG response. In addition, the data revealed that highly virulent HPAI virus and MERS-CoV induce repressive histone modifications, which downregulate expression of ISG subsets. Notably, influenza A virus NS1 appears to play a central role in this histone-mediated downregulation in highly pathogenic influenza strains. Together, the work demonstrates the existence of unique and common viral strategies for controlling the global ISG response and provides a novel avenue for viral antagonism via altered histone modifications.",2014 May 20,"['Menachery, Vineet D.', 'Eisfeld, Amie J.', 'Schäfer, Alexandra', 'Josset, Laurence', 'Sims, Amy C.', 'Proll, Sean', 'Fan, Shufang', 'Li, Chengjun', 'Neumann, Gabriele', 'Tilton, Susan C.', 'Chang, Jean', 'Gralinski, Lisa E.', 'Long, Casey', 'Green, Richard', 'Williams, Christopher M.', 'Weiss, Jeffrey', 'Matzke, Melissa M.', 'Webb-Robertson, Bobbie-Jo', 'Schepmoes, Athena A.', 'Shukla, Anil K.', 'Metz, Thomas O.', 'Smith, Richard D.', 'Waters, Katrina M.', 'Katze, Michael G.', 'Kawaoka, Yoshihiro', 'Baric, Ralph S.']",mBio,,,True
c09931fd77525099b75d2b2a0a99bce246e9ec0a,PMC,Severe virus influenza A H1N1 related pneumonia and community-acquired pneumonia: differences in the evolution,http://dx.doi.org/10.5935/0103-507X.20130023,PMC4031839,23917977,CC BY-NC,"OBJECTIVE: To analyze the clinical, laboratory and evolution data of patients with severe influenza A H1N1 pneumonia and compare the data with that of patients with severe community-acquired bacterial pneumonia. METHODS: Cohort and retrospective study. All patients admitted to the intensive care unit between May 2009 and December 2010 with a diagnosis of severe pneumonia caused by the influenza A H1N1 virus were included in the study. Thirty patients with severe community-acquired pneumonia admitted within the same period were used as a control group. Severe community-acquired pneumonia was defined as the presence of at least one major severity criteria (ventilator or vasopressor use) or two minor criteria. RESULTS: The data of 45 patients were evaluated. Of these patients, 15 were infected with H1N1. When compared to the group with community-acquired pneumonia, patients from the H1N1 group had significantly lower leukocyte counts on admission (6,728±4,070 versus 16,038±7,863; p<0.05) and lower C-reactive protein levels (Day 2: 15.1±8.1 versus 22.1±10.9 mg/dL; p<0.05). The PaO(2)/FiO(2) ratio values were lower in the first week in patients with H1N1. Patients who did not survive the H1N1 severe pneumonia had significantly higher levels of C-reactive protein and higher serum creatinine levels compared with patients who survived. The mortality rate was significantly higher in the H1N1 group than in the control group (53% versus 20%; p=0.056, respectivelly). CONCLUSION: Differences in the leukocyte count, C-reactive protein concentrations and oxygenation profiles may contribute to the diagnosis and prognosis of patients with severe influenza A H1N1 virus-related pneumonia and community-acquired pneumonia.",2013 Apr-Jun,"['Nardocci, Paula', 'Gullo, Caio Eduardo', 'Lobo, Suzana Margareth']",Rev Bras Ter Intensiva,,,True
6d28097d6542b0b34f34ca4d2359856cc461b5f5,PMC,Respiratory Syncytial Virus and Other Respiratory Viral Infections in Older Adults With Moderate to Severe Influenza-like Illness,http://dx.doi.org/10.1093/infdis/jit839,PMC4038137,24482398,CC BY-NC-ND,"Background. Few studies have prospectively assessed viral etiologies of acute respiratory infections in community-based elderly individuals. We assessed viral respiratory pathogens in individuals ≥65 years with influenza-like illness (ILI). Methods. Multiplex reverse-transcriptase polymerase chain reaction identified viral pathogens in nasal/throat swabs from 556 episodes of moderate-to-severe ILI, defined as ILI with pneumonia, hospitalization, or maximum daily influenza symptom severity score (ISS) >2. Cases were selected from a randomized trial of an adjuvanted vs nonadjuvanted influenza vaccine conducted in elderly adults from 15 countries. Results. Respiratory syncytial virus (RSV) was detected in 7.4% (41/556) moderate-to-severe ILI episodes in elderly adults. Most (39/41) were single infections. There was a significant association between country and RSV detection (P = .004). RSV prevalence was 7.1% (2/28) in ILI with pneumonia, 12.5% (8/64) in ILI with hospitalization, and 6.7% (32/480) in ILI with maximum ISS > 2. Any virus was detected in 320/556 (57.6%) ILI episodes: influenza A (104/556, 18.7%), rhinovirus/enterovirus (82/556, 14.7%), coronavirus and human metapneumovirus (each 32/556, 5.6%). Conclusions. This first global study providing data on RSV disease in ≥65 year-olds confirms that RSV is an important respiratory pathogen in the elderly. Preventative measures such as vaccination could decrease severe respiratory illnesses and complications in the elderly.",2014 Jun 15,"['Falsey, Ann R.', 'McElhaney, Janet E.', 'Beran, Jiri', 'van Essen, Gerrit A.', 'Duval, Xavier', 'Esen, Meral', 'Galtier, Florence', 'Gervais, Pierre', 'Hwang, Shinn-Jang', 'Kremsner, Peter', 'Launay, Odile', 'Leroux-Roels, Geert', 'McNeil, Shelly A.', 'Nowakowski, Andrzej', 'Richardus, Jan Hendrik', 'Ruiz-Palacios, Guillermo', 'St Rose, Suzanne', 'Devaster, Jeanne-Marie', 'Oostvogels, Lidia', 'Durviaux, Serge', 'Taylor, Sylvia']",J Infect Dis,,,True
cae1f2fd5785845caa42d6497361eba46a68f11d,PMC,Macrophage Polarization in Inflammatory Diseases,http://dx.doi.org/10.7150/ijbs.8879,PMC4046879,24910531,CC BY-NC-ND,"Diversity and plasticity are two hallmarks of macrophages. M1 macrophages (classically activated macrophages) are pro-inflammatory and have a central role in host defense against infection, while M2 macrophages (alternatively activated macrophages) are associated with responses to anti-inflammatory reactions and tissue remodeling, and they represent two terminals of the full spectrum of macrophage activation. Transformation of different phenotypes of macrophages regulates the initiation, development, and cessation of inflammatory diseases. Here we reviewed the characters and functions of macrophage polarization in infection, atherosclerosis, obesity, tumor, asthma, and sepsis, and proposed that targeting macrophage polarization and skewing their phenotype to adapt to the microenvironment might hold great promise for the treatment of inflammatory diseases.",2014 May 1,"['Liu, Yan-Cun', 'Zou, Xian-Biao', 'Chai, Yan-Fen', 'Yao, Yong-Ming']",Int J Biol Sci,,,True
9f5749af9a7d43c3e5e1ca056c71e5a9c0a0a1ae,PMC,Synthesis and characterization of different immunogenic viral nanoconstructs from rotavirus VP6 inner capsid protein,http://dx.doi.org/10.2147/IJN.S60014,PMC4047981,24936129,CC BY-NC,"In order to deliver low-cost viral capsomeres from a large amount of soluble viral VP6 protein from human rotavirus, we developed and optimized a biotechnological platform in Escherichia coli. Specifically, three different expression protocols were compared, differing in their genetic constructs, ie, a simple native histidine-tagged VP6 sequence, VP6 fused to thioredoxin, and VP6 obtained with the newly described small ubiquitin-like modifier (SUMO) fusion system. Our results demonstrate that the histidine-tagged protein does not escape the accumulation in the inclusion bodies, and that SUMO is largely superior to the thioredoxin-fusion tag in enhancing the expression and solubility of VP6 protein. Moreover, the VP6 protein produced according to the SUMO fusion tag displays well-known assembly properties, as observed in both transmission electron microscopy and atomic force microscopy images, giving rise to either VP6 trimers, 60 nm spherical virus-like particles, or nanotubes a few microns long. This different quaternary organization of VP6 shows a higher level of immunogenicity for the elongated structures with respect to the spheres or the protein trimers. Therefore, the expression and purification strategy presented here – providing a large amount of the viral capsid protein in the native form with relatively simple, rapid, and economical procedures – opens a new route toward large-scale production of a more efficient antigenic compound to be used as a vaccination tool or as an adjuvant, and also represents a top-quality biomaterial to be further modified for biotechnological purposes.",2014 May 30,"['Bugli, Francesca', 'Caprettini, Valeria', 'Cacaci, Margherita', 'Martini, Cecilia', 'Paroni Sterbini, Francesco', 'Torelli, Riccardo', 'Della Longa, Stefano', 'Papi, Massimiliano', 'Palmieri, Valentina', 'Giardina, Bruno', 'Posteraro, Brunella', 'Sanguinetti, Maurizio', 'Arcovito, Alessandro']",Int J Nanomedicine,,,True
9625e066a6643cb6078e629baf351bd93de6e671,PMC,Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis,http://dx.doi.org/10.1016/j.stemcr.2014.04.005,PMC4050357,24936469,CC BY-NC-ND,"Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.",2014 May 15,"['Chen, Lu', 'Coleman, Ronald', 'Leang, Ronika', 'Tran, Ha', 'Kopf, Alexandra', 'Walsh, Craig\xa0M.', 'Sears-Kraxberger, Ilse', 'Steward, Oswald', 'Macklin, Wendy\xa0B.', 'Loring, Jeanne\xa0F.', 'Lane, Thomas\xa0E.']",Stem Cell Reports,,,False
72e0e9c2d7ebfae9d3b3cfb3fbae4981744e7a2e,PMC,Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis,http://dx.doi.org/10.1016/j.stemcr.2014.04.005,PMC4050357,24936469,CC BY-NC-ND,"Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.",2014 May 15,"['Chen, Lu', 'Coleman, Ronald', 'Leang, Ronika', 'Tran, Ha', 'Kopf, Alexandra', 'Walsh, Craig\xa0M.', 'Sears-Kraxberger, Ilse', 'Steward, Oswald', 'Macklin, Wendy\xa0B.', 'Loring, Jeanne\xa0F.', 'Lane, Thomas\xa0E.']",Stem Cell Reports,,,False
e9f8ff46798ecd309d93570ed0eb669f23089a60,PMC,Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis,http://dx.doi.org/10.1016/j.stemcr.2014.04.005,PMC4050357,24936469,CC BY-NC-ND,"Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.",2014 May 15,"['Chen, Lu', 'Coleman, Ronald', 'Leang, Ronika', 'Tran, Ha', 'Kopf, Alexandra', 'Walsh, Craig\xa0M.', 'Sears-Kraxberger, Ilse', 'Steward, Oswald', 'Macklin, Wendy\xa0B.', 'Loring, Jeanne\xa0F.', 'Lane, Thomas\xa0E.']",Stem Cell Reports,,,False
5a65c75cbc18588b5cd6a73f403a7c7b27c06053,PMC,Informing U.S. Federal Public Health Preparation for Emerging Virus Pandemic Threats at Ports of Entry,http://dx.doi.org/10.5210/ojphi.v6i1.5122,PMC4050778,,CC BY-NC,,2014 Apr 29,"['Hickey, Andrew', 'Wong, Diana', 'Hendricks, Janet', 'Stephens, Michael', 'Pedersen, Erik', 'Carr, Deborah', 'Brown, Kandis', 'Grant, Christopher', 'Hobson, Jamie', 'Ruble, Jessica', 'Albrecht, William', 'Blackburn, Tajah', 'Marouf, Afif', 'Bodenhamer, Todd', 'Waters, Julie', 'Freese, Mark']",Online J Public Health Inform,,,False
db33628e5883348c9ef9d04fbb2042b1def33ca0,PMC,Village Doctors’ Acceptability to a Syndromic Surveillance System in Rural China,http://dx.doi.org/10.5210/ojphi.v6i1.5204,PMC4050779,,CC BY-NC,,2014 Apr 29,"['Fei, Yang', 'Ding, Yan', 'Xu, Biao', 'Nie, Shaofa', 'Yan, Weirong', 'Diwan, Vinod K.', 'Sauerborn, Rainer', 'Dong, Hengjin']",Online J Public Health Inform,,,False
7925057cfe0cb75ae6079879cb2d22d23e42dfa5,PMC,Searching for MERS and Novel Flu with Limited Resources,http://dx.doi.org/10.5210/ojphi.v6i1.5163,PMC4050803,,CC BY-NC,,2014 Apr 29,"['Siniscalchi, Alan', 'Ishikawa, Charlie']",Online J Public Health Inform,,,True
019edb72782a55f6322e563677de50f62f206294,PMC,The Evolution of the WHO/NREVSS Influenza Surveillance System: The Challenges and Opportunities that Accompany Electronic Laboratory Data,http://dx.doi.org/10.5210/ojphi.v6i1.5179,PMC4050831,,CC BY-NC,,2014 Apr 29,"Mustaquim, Desiree",Online J Public Health Inform,,,False
f477cb32c61ef1a690f4b9afe74d38f8e147f39f,PMC,Federal Interagency Interactions During Outbreaks of H7N9 Influenza and MERS-CoV,http://dx.doi.org/10.5210/ojphi.v6i1.5105,PMC4050833,,CC BY-NC,,2014 Apr 29,"['Bennett, Steve', 'Carr, Deborah', 'Freese, Mark', 'Hendricks, Janet', 'Stephens, Michael', 'Pedersen, Erik', 'Brown, Kandis', 'Grant, Christopher', 'Hobson, Jamie', 'Ruble, Jessica', 'Albrecht, William', 'Blackburn, Tajah', 'Boddenhamer, Todd', 'Quitugua, Teresa']",Online J Public Health Inform,,,True
77cdb9f7f5451fd710304093391bca2637411c85,PMC,Neutralizing antibody responses to enterovirus and adenovirus in healthy adults in China,http://dx.doi.org/10.1038/emi.2014.30,PMC4051363,26038738,CC BY-NC-SA,"Hand, foot and mouth disease (HFMD) is an important public health problem that has emerged over the past several years. HFMD predominantly infects children under seven years old and occasionally causes severe disease in adults. Among the enteroviruses, enterovirus 71 (EV71) and coxsackievirus 16 (CA16) are the major causative agents of HFMD. In addition, adenovirus cocirculates with enterovirus and has become a possible additional pathogenic factor for HFMD in some cases. Here, we have investigated the neutralizing antibody responses to both enterovirus and adenovirus in adults, with the aim of exploring the prevalence trends of these viruses and the nature of protective immunity in humans to these viral infections. Sera from 391 healthy adults from 21 provinces and cities in China were tested for the presence of antibodies against EV71, CA16, adenovirus human serotype 5 (AdHu5) and chimpanzee adenovirus pan7 (AdC7) using neutralization tests. High seroprevalence rates of EV71, CA16 and AdHu5 were found in the population (85.7%, 58.8% and 74.2%, respectively). The coseropositivity rate of these three viruses was 39.4% (154 of 391), with median neutralizing antibody titers of 80, 40 and 640, respectively, and the neutralizing antibody titer for EV71 was found to be correlated with those of CA16 and AdHu5. AdC7 was found to be a rare adenovirus serotype in the human population, with a seropositivity rate of 11.8%, suggesting that it could be a good choice for a vaccine carrier that could be used in vaccine development.",2014 May 7,"['Wang, Xiang', 'Xing, Man', 'Zhang, Chao', 'Yang, Yong', 'Chi, Yudan', 'Tang, Xinying', 'Zhang, Hongbo', 'Xiong, Sidong', 'Yu, Luogang', 'Zhou, Dongming']",Emerg Microbes Infect,,,True
4615c0a2b164f98ac850d2c16f24cfe5a33db75d,PMC,Analysis of interactions between SNARE proteins using imaging ellipsometer coupled with microfluidic array,http://dx.doi.org/10.1038/srep05341,PMC4061542,24938428,CC BY-NC-SA,"The soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins are small and abundant membrane-bound proteins, whose specific interactions mediate membrane fusion during cell fusion or cellular trafficking. In this study, we report the use of a label-free method, called imaging ellipsometer to analyze the interactions among three SNAREs, namely Sec22p, Ykt6p and Sso2p. The SNAREs were immobilized on the silicon wafer and then analyzed in a pairwise mode with microfluidic array, leading us to discover the interactions between Ykt6p and Sso2p, Sec22p and Sso2p. Moreover, by using the real-time function of the imaging ellipsometer, we were able to obtain their association constants (K(A)) of about 10(4) M(−1). We argue that the use of imaging ellipsometer coupled with microfluidic device will deepen our understanding of the molecular mechanisms underlying membrane fusion process.",2014 Jun 18,"['Qi, Cai', 'Zhang, Hong', 'Liu, Li', 'Yang, Yinke', 'Kang, Tengfei', 'Hao, Wenxin', 'Jin, Gang', 'Jiang, Taijiao']",Sci Rep,,,True
c4ebb70ed5546353d7221bf693b4e990ab9e41cb,PMC,Analysis of interactions between SNARE proteins using imaging ellipsometer coupled with microfluidic array,http://dx.doi.org/10.1038/srep05341,PMC4061542,24938428,CC BY-NC-SA,"The soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins are small and abundant membrane-bound proteins, whose specific interactions mediate membrane fusion during cell fusion or cellular trafficking. In this study, we report the use of a label-free method, called imaging ellipsometer to analyze the interactions among three SNAREs, namely Sec22p, Ykt6p and Sso2p. The SNAREs were immobilized on the silicon wafer and then analyzed in a pairwise mode with microfluidic array, leading us to discover the interactions between Ykt6p and Sso2p, Sec22p and Sso2p. Moreover, by using the real-time function of the imaging ellipsometer, we were able to obtain their association constants (K(A)) of about 10(4) M(−1). We argue that the use of imaging ellipsometer coupled with microfluidic device will deepen our understanding of the molecular mechanisms underlying membrane fusion process.",2014 Jun 18,"['Qi, Cai', 'Zhang, Hong', 'Liu, Li', 'Yang, Yinke', 'Kang, Tengfei', 'Hao, Wenxin', 'Jin, Gang', 'Jiang, Taijiao']",Sci Rep,,,False
af82e1f7e181393a18fb017ee98abdb17fb78d42,PMC,Hemophagocytic lymphohistiocytosis: review of etiologies and management,http://dx.doi.org/10.2147/JBM.S46255,PMC4062561,24966707,CC BY-NC,"Hemophagocytic lymphohistiocytosis (HLH) covers a wide array of related life-threatening conditions featuring ineffective immunity characterized by an uncontrolled hyperinflammatory response. HLH is often triggered by infection. Familial forms result from genetic defects in natural killer cells and cytotoxic T-cells, typically affecting perforin and intracellular vesicles. HLH is likely under-recognized, which contributes to its high morbidity and mortality. Early recognition is crucial for any reasonable attempt at curative therapy to be made. Current treatment regimens include immunosuppression, immune modulation, chemotherapy, and biological response modification, followed by hematopoietic stem-cell transplant (bone marrow transplant). A number of recent studies have contributed to the understanding of HLH pathophysiology, leading to alternate treatment options; however, much work remains to raise awareness and improve the high morbidity and mortality of these complex conditions.",2014 Jun 12,"George, Melissa R",J Blood Med,,,True
43aeebc83e75673430343bc8f01df5a96793b217,PMC,Streptococcus suis infection: An emerging/reemerging challenge of bacterial infectious diseases?,http://dx.doi.org/10.4161/viru.28595,PMC4063810,24667807,CC BY-NC,"Streptococcus suis (S. suis) is a family of pathogenic gram-positive bacterial strains that represents a primary health problem in the swine industry worldwide. S. suis is also an emerging zoonotic pathogen that causes severe human infections clinically featuring with varied diseases/syndromes (such as meningitis, septicemia, and arthritis). Over the past few decades, continued efforts have made significant progress toward better understanding this zoonotic infectious entity, contributing in part to the elucidation of the molecular mechanism underlying its high pathogenicity. This review is aimed at presenting an updated overview of this pathogen from the perspective of molecular epidemiology, clinical diagnosis and typing, virulence mechanism, and protective antigens contributing to its zoonosis.",2014 May 15,"['Feng, Youjun', 'Zhang, Huimin', 'Wu, Zuowei', 'Wang, Shihua', 'Cao, Min', 'Hu, Dan', 'Wang, Changjun']",Virulence,,,True
96a2891a55f0d6076cd89b09e8571d4ce262fbc7,PMC,Molecular Epidemiology of Paramyxoviruses in Frugivorous Eidolon helvum Bats in Zambia,http://dx.doi.org/10.1292/jvms.13-0518,PMC4064153,24389743,CC BY-NC-ND,"In this study, we describe the detection of novel paramyxoviruses from the Eidolon helvum species of fruit bats. We extracted RNA from 312 spleen samples from bats captured in Zambia over a period of 4 years (2008–2011). Semi-nested RT-PCR detected a total of 25 (8%) positive samples for paramyxoviruses which were then directly sequenced and analyzed using phylogenetic analysis. Among the positive samples, seven novel paramyxoviruses were detected. Five viruses were closely related to the genus Henipavirus, while two viruses were related to the unclassified Bat paramyxoviruses from Ghana and Congo Brazzaville. Our study identified novel Henipavirus-related and unrelated viruses using RT-PCR in fruit bats from Kansaka National Park and indicated the presence of similar Bat paramyxoviruses originating from wide geographic areas, suggesting the ability of bats to harbor and transmit viruses. The presence of these viruses in fruit bats might pose a public health risk.",2014 Apr 31,"['MULEYA, Walter', 'SASAKI, Michihito', 'ORBA, Yasuko', 'ISHII, Akihiro', 'THOMAS, Yuka', 'NAKAGAWA, Emiko', 'OGAWA, Hirohito', 'HANG’OMBE, Bernard', 'NAMANGALA, Boniface', 'MWEENE, Aaron', 'TAKADA, Ayato', 'KIMURA, Takashi', 'SAWA, Hirofumi']",J Vet Med Sci,,,True
308e7d99fefced3b130b780416ecef0278d2fe41,PMC,"Community-Based Risk Communication Survey: Risk Prevention Behaviors in Communities during the H1N1 crisis, 2010",http://dx.doi.org/10.1016/j.phrp.2013.12.001,PMC4064644,24955307,CC BY-NC,"OBJECTIVES: The present study aimed to investigate the prevalence of and factors associated with H1N1 preventive behaviors in a community-based population. METHODS: A cross-sectional study was conducted in three urban and two rural communities in Korea. Interviews were conducted with 3462 individuals (1608 men and 1854 women) aged ≥ 19 years during February–March 2010. Influenza-related information including anxiety, preventive behaviors and their perceived effectiveness, vaccination status, past influenza-like illness symptoms, and sources of and trust in information was obtained. RESULTS: Among 3462 participants, 173 reported experiencing influenza-like illness symptoms within the past 12 months. The mean H1N1 preventive behavior score was 25.5 ± 5.5 (out of a possible 40). The percent of participants reporting high perceived effectiveness and high anxiety was 46.2% and 21.4%, respectively. After controlling for potential confounders, H1N1 preventive behavior scores were predicted by a high (β = 3.577, p < 0.001) or moderate (β = 2.529, p < 0.001) perception of their effectiveness. Similarly, moderate (β = 1.516, p < 0.001) and high (β = 4.103, p < 0.001) anxiety scores predicted high preventive behavior scores. CONCLUSION: Effective methods of promoting population behavior change may be nationwide campaigns through mass media, as well as education and promotion by health care providers and broadcasters.",2014 Feb 10,"['Kim, Soo Jeong', 'Han, Jin A.', 'Lee, Tae-Yong', 'Hwang, Tae-Yoon', 'Kwon, Keun-Sang', 'Park, Ki Soo', 'Lee, Kyung Jong', 'Kim, Moon Shik', 'Lee, Soon Young']",Osong Public Health Res Perspect,,,False
b3c6008294a172e0609ee1467e87ec64ad242985,PMC,Standards for Sequencing Viral Genomes in the Era of High-Throughput Sequencing,http://dx.doi.org/10.1128/mBio.01360-14,PMC4068259,24939889,CC BY-NC-SA,"Thanks to high-throughput sequencing technologies, genome sequencing has become a common component in nearly all aspects of viral research; thus, we are experiencing an explosion in both the number of available genome sequences and the number of institutions producing such data. However, there are currently no common standards used to convey the quality, and therefore utility, of these various genome sequences. Here, we propose five “standard” categories that encompass all stages of viral genome finishing, and we define them using simple criteria that are agnostic to the technology used for sequencing. We also provide genome finishing recommendations for various downstream applications, keeping in mind the cost-benefit trade-offs associated with different levels of finishing. Our goal is to define a common vocabulary that will allow comparison of genome quality across different research groups, sequencing platforms, and assembly techniques.",2014 Jun 17,"['Ladner, Jason T.', 'Beitzel, Brett', 'Chain, Patrick S. G.', 'Davenport, Matthew G.', 'Donaldson, Eric', 'Frieman, Matthew', 'Kugelman, Jeffrey', 'Kuhn, Jens H.', 'O’Rear, Jules', 'Sabeti, Pardis C.', 'Wentworth, David E.', 'Wiley, Michael R.', 'Yu, Guo-Yun', None, 'Sozhamannan, Shanmuga', 'Bradburne, Christopher', 'Palacios, Gustavo']",mBio,,,True
3e66fa6e5fa282546d206b4d2c55ad15f38f7563,PMC,Influenza A (H1N1) pneumonia: HRCT findings,http://dx.doi.org/10.1590/S1806-37132013000300009,PMC4075839,23857688,CC BY-NC,"OBJECTIVE: To describe aspects found on HRCT scans of the chest in patients infected with the influenza A (H1N1) virus. METHODS: We retrospectively analyzed the HRCT scans of 71 patients (38 females and 33 males) with H1N1 infection, confirmed through laboratory tests, between July and September of 2009. The HRCT scans were interpreted by two thoracic radiologists independently, and in case of disagreement, the decisions were made by consensus. RESULTS: The most common HRCT findings were ground-glass opacities (85%), consolidation (64%), or a combination of ground-glass opacities and consolidation (58%). Other findings were airspace nodules (25%), bronchial wall thickening (25%), interlobular septal thickening (21%), crazy-paving pattern (15%), perilobular pattern (3%), and air trapping (3%). The findings were frequently bilateral (89%), with a random distribution (68%). Pleural effusion, when observed, was typically minimal. No lymphadenopathy was identified. CONCLUSIONS: The most common findings were ground-glass opacities and consolidations, or a combination of both. Involvement was commonly bilateral with no axial or craniocaudal predominance in the distribution. Although the major tomographic findings in H1N1 infection are nonspecific, it is important to recognize such findings in order to include infection with the H1N1 virus in the differential diagnosis of respiratory symptoms.",2013 May-Jun,"['Amorim, Viviane Brandão', 'Rodrigues, Rosana Souza', 'Barreto, Miriam Menna', 'Zanetti, Gláucia', 'Hochhegger, Bruno', 'Marchiori, Edson']",J Bras Pneumol,,,True
ea08d7bb1c95436e9ed7af4ed5419cc8fc56e7b7,PMC,Immunogenicity and efficacy of a plasmid DNA rabies vaccine incorporating Myd88 as a genetic adjuvant,http://dx.doi.org/10.7774/cevr.2014.3.2.202,PMC4083073,25003094,CC BY-NC,"PURPOSE: Myeloid differentiation factor 88 (Myd88), a ubiquitous Toll-like receptor adaptor molecule, has been reported to play important roles in B cell responses to infections and vaccination. The present study evaluated the effects of genetic adjuvanting with Myd88 on the immune responses to a plasmid DNA rabies vaccine. MATERIALS AND METHODS: Plasmids encoding rabies glycoprotein alone (pIRES-Rgp) or a fragment of Myd88 gene in addition (pIRES-Rgp-Myd) were constructed and administered intramuscularly or intrademally in Swiss albino mice (on days 0, 7, and 21). Rabies virus neutralizing antibody (RVNA) titres were estimated in the mice sera on days 14 and 28 by rapid fluorescent focus inhibition test. The protective efficacy of the constructs was evaluated by an intracerebral challenge with challenge virus standard virus on day 35. RESULTS: Co-expression of Myd88 increased RVNA responses to pIRES-Rgp by 3- and 2-folds, following intramuscular and intradermal immunization, respectively. pIRES-Rgp protected 80% of the mice following intramuscular and intradermal immunizations, while pIRES-Rgp-Myd afforded 100% protection following similar administrations. CONCLUSION: Genetic adjuvanting with Myd88 enhanced the RVNA responses and protective efficacy of a plasmid DNA rabies vaccine. This strategy might be useful for rabies vaccination of canines in the field, and needs further evaluation.",2014 Jul 20,"['Ullas, Padinjaremattathil Thankappan', 'Desai, Anita', 'Madhusudana, Shampur Narayan']",Clin Exp Vaccine Res,,,True
358c7b35017efdc0b8895850ef2caba0cccea638,PMC,Guidelines for vaccination of dogs and cats in Korea,http://dx.doi.org/10.7774/cevr.2014.3.2.244,PMC4083078,25003099,CC BY-NC,"This guideline contains the recommended vaccination schedules of dogs and cats from World Small Animal Veterinary Association (WSAVA) and American Animal Hospital Association (AAHA). In 2010, WSAVA published guidelines for the vaccination of dogs and cats. And, in 2011, AAHA also published guidelines for vaccination of dogs. In Korea, there is no published guideline for vaccination of dogs and cats yet. Therefore, the plane of vaccination also reports the present situation of vaccination schedule of dogs and cats in Korean animal hospitals.",2014 Jul 20,"['Song, Woo-Jin', 'Kim, Hyun-Tae', 'Yoo, Han-Sang', 'Youn, Hwa-Young']",Clin Exp Vaccine Res,,,False
22238e30828eb4613d777bea7bd3ff321aae450c,PMC,"Travel-acquired infections and illnesses in Canadians: surveillance report from CanTravNet surveillance data, 2009–2011",,PMC4085092,25009682,CC BY-SA,"BACKGROUND: Important knowledge gaps exist in our understanding of migration medicine practice and the impact of pathogens imported by Canadian travellers. We present here a comprehensive, Canada-specific surveillance summary of illness in a cohort of returned Canadian travellers and new immigrants. METHODS: We extracted and analyzed (using standard parametric and nonparametric techniques) data from the Canadian Travel Medicine Network (CanTravNet) database for ill returned Canadian travellers and new immigrants who presented to a Canadian GeoSentinel Surveillance Network site between September 2009 and September 2011. RESULTS: During the study period, 4365 travellers and immigrants presented to a CanTravNet site, 3943 (90.3%) of whom were assigned a travel-related diagnosis. Among the 3115 non-immigrant travellers with a definitive travel-related diagnosis, arthropod bite (n = 127 [4.1%]), giardiasis (n = 91 [2.9%]), malaria (n = 77 [2.5%]), latent tuberculosis (n = 73 [2.3%]), and strongyloidiasis (n = 66 [2.1%]) were the most common specific etiologic diagnoses. Among the 828 immigrants with definitive travel-related diagnoses, the most frequent etiologies were latent tuberculosis (n = 229 [27.7%]), chronic hepatitis B (n = 182 [22.0%]), active tuberculosis (n = 97 [11.7%]), chronic hepatitis C (n = 89 [10.7%]), and strongyloidiasis (n = 41 [5.0%]). Potentially serious infections, such as dengue fever (61 cases) and enteric fever due to Salmonella enterica serotype Typhi or Paratyphi (36 cases), were common. Individuals travelling for the purpose of visiting friends and relatives (n = 500 [11.6% of those with known reason for travel]) were over-represented among those diagnosed with malaria and enteric fever, compared with other illnesses (for malaria 34/94 [36.2%] v. 466/4221 [11.0%]; for enteric fever, 17/36 [47.2%] v. 483/4279 [11.3%]) (both p < 0.001). For cases of malaria, there was also overrepresentation (compared with other illnesses) from business travellers (22/94 [23.4%] v. 337/4221 [8.0%]) and males (62/94 [66.0%] v. 1964/4269 [46.0%]) (both p < 0.001). Malaria was more likely than other illnesses to be acquired in sub-Saharan Africa (p < 0.001), whereas dengue was more likely than other illnesses to be imported from the Caribbean and South East Asia (both p = 0.003) and enteric fever from South Central Asia (24/36 [66.7%]) (p < 0.001). INTERPRETATION: This analysis of surveillance data on ill returned Canadian travellers has detailed the spectrum of imported illness within this cohort. It provides an epidemiologic framework for Canadian practitioners encountering ill returned travellers. We have confirmed that travel to visit friends and relatives confers particularly high risks, which underscores the need to improve pretravel intervention for a population that is unlikely to seek specific pretravel advice. Potentially serious and fatal illnesses such as malaria and enteric fever were common, as were illnesses of public health importance, such as tuberculosis and hepatitis B.",2014 Feb 11,"['Boggild, Andrea K', 'Geduld, Jennifer', 'Libman, Michael', 'Ward, Brian J', 'McCarthy, Anne E', 'Doyle, Patrick W', 'Ghesquiere, Wayne', 'Vincelette, Jean', 'Kuhn, Susan', 'Freedman, David O', 'Kain, Kevin C']",Open Med,,,True
ba581ccb585036d6220cfb461733c94584326d96,PMC,Back to basics: hand hygiene and isolation,http://dx.doi.org/10.1097/QCO.0000000000000080,PMC4086774,24945613,CC BY-NC-ND,"PURPOSE OF REVIEW: Hand hygiene and isolation are basic, but very effective, means of preventing the spread of pathogens in healthcare. Although the principle may be straightforward, this review highlights some of the controversies regarding the implementation and efficacy of these interventions. RECENT FINDINGS: Hand hygiene compliance is an accepted measure of quality and safety in many countries. The evidence for the efficacy of hand hygiene in directly reducing rates of hospital-acquired infections has strengthened in recent years, particularly in terms of reduced rates of staphylococcal sepsis. Defining the key components of effective implementation strategies and the ideal method(s) of assessing hand hygiene compliance are dependent on a range of factors associated with the healthcare system. Although patient isolation continues to be an important strategy, particularly in outbreaks, it also has some limitations and can be associated with negative effects. Recent detailed molecular epidemiology studies of key healthcare-acquired pathogens have questioned the true efficacy of isolation, alone as an effective method for the routine prevention of disease transmission. SUMMARY: Hand hygiene and isolation are key components of basic infection control. Recent insights into the benefits, limitations and even adverse effects of these interventions are important for their optimal implementation.",2014 Aug 2,"['Lin Huang, G. Khai', 'Stewardson, Andrew J.', 'Lindsay Grayson, M.']",Curr Opin Infect Dis,,,True
41deae1169912161f5195d978626aa2ca1898994,PMC,Production and immunogenicity of chimeric virus-like particles containing the spike glycoprotein of infectious bronchitis virus,http://dx.doi.org/10.4142/jvs.2014.15.2.209,PMC4087222,24378590,CC BY-NC,"Infectious bronchitis virus (IBV) poses a severe threat to the poultry industry and causes heavy economic losses worldwide. Vaccination is the most effective method of preventing infection and controlling the spread of IBV, but currently available inactivated and attenuated virus vaccines have some disadvantages. We developed a chimeric virus-like particle (VLP)-based candidate vaccine for IBV protection. The chimeric VLP was composed of matrix 1 protein from avian influenza H5N1 virus and a fusion protein neuraminidase (NA)/spike 1 (S1) that was generated by fusing IBV S1 protein to the cytoplasmic and transmembrane domains of NA protein of avian influenza H5N1 virus. The chimeric VLPs elicited significantly higher S1-specific antibody responses in intramuscularly immunized mice and chickens than inactivated IBV viruses. Furthermore, the chimeric VLPs induced significantly higher neutralization antibody levels than inactivated H120 virus in SPF chickens. Finally, the chimeric VLPs induced significantly higher IL-4 production in mice. These results demonstrate that chimeric VLPs have the potential for use in vaccines against IBV infection.",2014 Jun 16,"['Lv, Lishan', 'Li, Xiaoming', 'Liu, Genmei', 'Li, Ran', 'Liu, Qiliang', 'Shen, Huifang', 'Wang, Wei', 'Xue, Chunyi', 'Cao, Yongchang']",J Vet Sci,,,True
02106ae9d442c7c97a8e95a4d27d2af5916b04cb,PMC,Etiology and Clinical Outcomes of Acute Respiratory Virus Infection in Hospitalized Adults,http://dx.doi.org/10.3947/ic.2014.46.2.67,PMC4091371,25024868,CC BY-NC,"BACKGROUND: Etiologies and clinical profiles of acute respiratory viral infections need to be clarified to improve preventive and therapeutic strategies. MATERIALS AND METHODS: A retrospective observational study at a single, university-affiliated center was performed to evaluate the respiratory viral infection etiologies in children compared to that in adults and to document the clinical features of common viral infections for adults from July 2009 to April 2012. RESULTS: The common viruses detected from children (2,800 total patients) were human rhinovirus (hRV) (31.8%), adenovirus (AdV) (19.2%), respiratory syncytial virus (RSV) A (17.4%), RSV B (11.7%), and human metapneumovirus (hMPV) (9.8%). In comparison, influenza virus A (IFA) had the highest isolation rate (28.5%), followed by hRV (15.5%), influenza virus B (IFB) (15.0%), and hMPV (14.0%), in adults (763 total patients). Multiple viruses were detected in single specimens from 22.4% of children and 2.0% of adults. IFA/IFB, RSV A/B, and hMPV exhibited strong seasonal detection and similar circulating patterns in children and adults. Adult patients showed different clinical manifestations according to causative viruses; nasal congestion and rhinorrhea were more common in hRV and human coronavirus (hCoV) infection. Patients with RSV B, hRV, or AdV tended to be younger, and those infected with RSV A and hMPV were likely to be older. Those with RSV A infection tended to stay longer in hospital, enter the intensive care unit more frequently, and have a fatal outcome more often. The bacterial co-detection rate was 26.5%, and those cases were more likely to have lower respiratory tract involvement (P = 0.001), longer hospital stay (P = 0.001), and higher mortality (P = 0.001). CONCLUSIONS: The etiologic virus of an acute respiratory infection can be cautiously inferred based on a patient's age and clinical features and concurrent epidemic data. Large-scale prospective surveillance studies are required to provide more accurate information about respiratory viral infection etiology, which could favorably influence clinical outcomes.",2014 Jun 20,"['Seo, Yu Bin', 'Song, Joon Young', 'Choi, Min Ju', 'Kim, In Seon', 'Yang, Tea Un', 'Hong, Kyung-Wook', 'Cheong, Hee Jin', 'Kim, Woo Joo']",Infect Chemother,,,False
f3469557b37bfea7f3aebded4172020ad1d6e484,PMC,Construction of fat1 Gene Expression Vector and Its Catalysis Efficiency in Bovine Fetal Fibroblast Cells,http://dx.doi.org/10.5713/ajas.2011.11495,PMC4093122,25049605,CC BY-NC,"The FAT-1 protein is an n-3 fatty acid desaturase, which can recognize a range of 18- and 20-carbon n-6 substrates and transform n-6 polyunsaturated fatty acids (PUFAs) into n-3 PUFAs while n-3 PUFAs have beneficial effect on human health. Fat1 gene is the coding sequence from Caenorhabditis elegans which might play an important role on lipometabolism. To reveal the function of fat1 gene in bovine fetal fibroblast cells and gain the best cell nuclear donor for transgenic bovines, the codon of fat1 sequence was optimized based on the codon usage frequency preference of bovine muscle protein, and directionally cloned into the eukaryotic expression vector pEF-GFP. After identifying by restrictive enzyme digests with AatII/XbaI and sequencing, the fusion plasmid pEF-GFP-fat1 was identified successfully. The pEF-GFP-fat1 vector was transfected into bovine fetal fibroblast cells mediated by Lipofectamine2000(TM). The positive bovine fetal fibroblast cells were selected by G418 and detected by RT-PCR. The results showed that a 1,234 bp transcription was amplified by reverse transcription PCR and the positive transgenic fat1 cell line was successfully established. Then the expression level of fat1 gene in positive cells was detected using quantitative PCR, and the catalysis efficiency was detected by gas chromatography. The results demonstrated that the catalysis efficiency of fat1 was significantly high, which can improve the total PUFAs rich in EPA, DHA and DPA. Construction and expression of pEF-GFP-fat1 vector should be helpful for further understanding the mechanism of regulation of fat1 in vitro. It could also be the first step in the production of fat1 transgenic cattle.",2012 May 1,"['Liu, Boyang', 'Yang, Runjun', 'Li, Junya', 'Zhang, Lupei', 'Liu, Jing', 'Lu, Chunyan', 'Lian, Chuanjiang', 'Li, Zezhong', 'Zhang, Yonghong', 'Zhang, Liying', 'Zhao, Zhihui']",Asian-Australas J Anim Sci,,,True
bbfbefd19c9c471dbacabd1f57124d1ad36f24f5,PMC,Selection of Reference Genes for Gene Expression Studies in Porcine Whole Blood and Peripheral Blood Mononuclear Cells under Polyinosinic:Polycytidylic Acid Stimulation,http://dx.doi.org/10.5713/ajas.2013.13471,PMC4093518,25049976,CC BY-NC,"Investigating gene expression of immune cells of whole blood or peripheral blood mononuclear cells (PBMC) under polyinosinic:polycytidylic acid (poly I:C) stimulation is valuable for understanding the immune response of organism to RNA viruses. Quantitative real-time PCR (qRT-PCR) is a standard method for quantification of gene expression studies. However, the reliability of qRT-PCR data critically depends on proper selection of reference genes. In the study, using two different analysis programs, geNorm and NormFinder, we systematically evaluated the gene expression stability of six candidate reference genes (GAPDH, ACTB, B2M, RPL4, TBP, and PPIA) in samples of whole blood and PBMC with or without poly I:C stimulation. Generally, the six candidate genes performed a similar trend of expression stability in the samples of whole blood and PBMC, but more stably expressed in whole blood than in PBMC. geNorm ranked B2M and PPIA as the best combination for gene expression normalization, while according to NormFinder, TBP was ranked as the most stable reference gene, followed by B2M and PPIA. Comprehensively considering the results from the two programs, we recommended using the geometric mean of the three genes, TBP, PPIA and B2M, to normalize the gene expression of whole blood and PBMC with poly I:C stimulation. Our study is the first detailed survey of the gene expression stability in whole blood and PBMC with or without poly I:C stimulation and should be helpful for investigating the molecular mechanism involved in porcine whole blood and PBMC in response to poly I:C stimulation.",2014 Apr,"['Wang, Jiying', 'Wang, Yanping', 'Wang, Huaizhong', 'Hao, Xiaojing', 'Wu, Ying', 'Guo, Jianfeng']",Asian-Australas J Anim Sci,,,True
a8873fbbee1ac5f4f5f62cc9b01bc7d63ea0f856,PMC,Selection of Reference Genes for Gene Expression Studies in Porcine Whole Blood and Peripheral Blood Mononuclear Cells under Polyinosinic:Polycytidylic Acid Stimulation,http://dx.doi.org/10.5713/ajas.2013.13471,PMC4093518,25049976,CC BY-NC,"Investigating gene expression of immune cells of whole blood or peripheral blood mononuclear cells (PBMC) under polyinosinic:polycytidylic acid (poly I:C) stimulation is valuable for understanding the immune response of organism to RNA viruses. Quantitative real-time PCR (qRT-PCR) is a standard method for quantification of gene expression studies. However, the reliability of qRT-PCR data critically depends on proper selection of reference genes. In the study, using two different analysis programs, geNorm and NormFinder, we systematically evaluated the gene expression stability of six candidate reference genes (GAPDH, ACTB, B2M, RPL4, TBP, and PPIA) in samples of whole blood and PBMC with or without poly I:C stimulation. Generally, the six candidate genes performed a similar trend of expression stability in the samples of whole blood and PBMC, but more stably expressed in whole blood than in PBMC. geNorm ranked B2M and PPIA as the best combination for gene expression normalization, while according to NormFinder, TBP was ranked as the most stable reference gene, followed by B2M and PPIA. Comprehensively considering the results from the two programs, we recommended using the geometric mean of the three genes, TBP, PPIA and B2M, to normalize the gene expression of whole blood and PBMC with poly I:C stimulation. Our study is the first detailed survey of the gene expression stability in whole blood and PBMC with or without poly I:C stimulation and should be helpful for investigating the molecular mechanism involved in porcine whole blood and PBMC in response to poly I:C stimulation.",2014 Apr,"['Wang, Jiying', 'Wang, Yanping', 'Wang, Huaizhong', 'Hao, Xiaojing', 'Wu, Ying', 'Guo, Jianfeng']",Asian-Australas J Anim Sci,,,False
963c0263d2acd998d323aabd13c7c103bb44f6d3,PMC,Reconstructing propagation networks with natural diversity and identifying hidden sources,http://dx.doi.org/10.1038/ncomms5323,PMC4104449,25014310,CC BY-NC-SA,"Our ability to uncover complex network structure and dynamics from data is fundamental to understanding and controlling collective dynamics in complex systems. Despite recent progress in this area, reconstructing networks with stochastic dynamical processes from limited time series remains to be an outstanding problem. Here we develop a framework based on compressed sensing to reconstruct complex networks on which stochastic spreading dynamics take place. We apply the methodology to a large number of model and real networks, finding that a full reconstruction of inhomogeneous interactions can be achieved from small amounts of polarized (binary) data, a virtue of compressed sensing. Further, we demonstrate that a hidden source that triggers the spreading process but is externally inaccessible can be ascertained and located with high confidence in the absence of direct routes of propagation from it. Our approach thus establishes a paradigm for tracing and controlling epidemic invasion and information diffusion in complex networked systems.",2014 Jul 11,"['Shen, Zhesi', 'Wang, Wen-Xu', 'Fan, Ying', 'Di, Zengru', 'Lai, Ying-Cheng']",Nat Commun,,,True
a34f8d05e44966a5fa2a8bdcf553d3533f1851d8,PMC,Reconstructing propagation networks with natural diversity and identifying hidden sources,http://dx.doi.org/10.1038/ncomms5323,PMC4104449,25014310,CC BY-NC-SA,"Our ability to uncover complex network structure and dynamics from data is fundamental to understanding and controlling collective dynamics in complex systems. Despite recent progress in this area, reconstructing networks with stochastic dynamical processes from limited time series remains to be an outstanding problem. Here we develop a framework based on compressed sensing to reconstruct complex networks on which stochastic spreading dynamics take place. We apply the methodology to a large number of model and real networks, finding that a full reconstruction of inhomogeneous interactions can be achieved from small amounts of polarized (binary) data, a virtue of compressed sensing. Further, we demonstrate that a hidden source that triggers the spreading process but is externally inaccessible can be ascertained and located with high confidence in the absence of direct routes of propagation from it. Our approach thus establishes a paradigm for tracing and controlling epidemic invasion and information diffusion in complex networked systems.",2014 Jul 11,"['Shen, Zhesi', 'Wang, Wen-Xu', 'Fan, Ying', 'Di, Zengru', 'Lai, Ying-Cheng']",Nat Commun,,,True
a70f7904950bba73ba43df71226c57344b28aa33,PMC,DIFFERENTIAL DIAGNOSIS OF RESPIRATORY VIRUSES BY USING REAL TIME RT-PCR METHODOLOGY,http://dx.doi.org/10.1590/S0036-46652013000600012,PMC4105094,24213199,CC BY-NC,,2013 Nov-Dec,"['Paulino, Renato de Souza', 'Benega, Margarete Aparecida', 'Santos, Katia Corrêa de Oliveira', 'da Silva, Daniela Bernardes Borges', 'Pereira, Juliana Cristina', 'Sasaki, Norio Augusto', 'Silva, Patricia Evelin', 'Curti, Suely Pires', 'Oliveira, Maria Isabel', 'R.M.P. Carvalhanas, Telma', 'Peret, Teresa', 'Erdman, Dean', 'de Paiva, Terezinha Maria']",Rev Inst Med Trop Sao Paulo,,,True
276ff0fe5b27771bb52e6fec57cfe7b6430c3b1d,PMC,Association between the level of antibodies in bulk tank milk and bovine respiratory syncytial virus exposure in the herd,http://dx.doi.org/10.1136/vr.102403,PMC4112425,24864076,CC BY-NC,"Antibody levels in bulk tank milk (BTM) against bovine respiratory syncytial virus (BRSV) are used to classify BRSV status of herds. The aim of this study was to investigate how these levels correspond with the time at which the herds were infected. Bulk tank milk, individual milk and serum samples from cows and young stock were investigated using an indirect ELISA. Screenings of BTM from 89 dairy herds during two winter seasons revealed a prevalence of positive herds from 82 per cent to 85 per cent. Eleven herds showed a marked increase in antibody levels between two screenings, indicating new infection. However, two of these herds had been free from BRSV for the last five to seven years. Two newly infected herds were monitored for four years and did not appear to get reinfected. Surprisingly, the BTM antibody levels in these herds remained high throughout the study period, but fluctuated significantly. This shows that the levels of antibodies in BTM can remain high for several years, even in herds where reinfection does not occur. BTM serology is a useful tool in the monitoring of infectious diseases in dairy herds, but has limitations as a diagnostic tool for BRSV infections.",2014 Jul 12,"['Klem, T. B.', 'Tollersrud, T.', 'Østerås, O.', 'Stokstad, M.']",Vet Rec,,,True
df1b6713549bcbe22ec020aaf62275280f096b9a,PMC,Viability of Pseudomonas aeruginosa in cough aerosols generated by persons with cystic fibrosis,http://dx.doi.org/10.1136/thoraxjnl-2014-205213,PMC4112489,24743559,CC BY-NC,"BACKGROUND: Person-to-person transmission of respiratory pathogens, including Pseudomonas aeruginosa, is a challenge facing many cystic fibrosis (CF) centres. Viable P aeruginosa are contained in aerosols produced during coughing, raising the possibility of airborne transmission. METHODS: Using purpose-built equipment, we measured viable P aeruginosa in cough aerosols at 1, 2 and 4 m from the subject (distance) and after allowing aerosols to age for 5, 15 and 45 min in a slowly rotating drum to minimise gravitational settling and inertial impaction (duration). Aerosol particles were captured and sized employing an Anderson Impactor and cultured using conventional microbiology. Sputum was also cultured and lung function and respiratory muscle strength measured. RESULTS: Nineteen patients with CF, mean age 25.8 (SD 9.2) years, chronically infected with P aeruginosa, and 10 healthy controls, 26.5 (8.7) years, participated. Viable P aeruginosa were detected in cough aerosols from all patients with CF, but not from controls; travelling 4 m in 17/18 (94%) and persisting for 45 min in 14/18 (78%) of the CF group. Marked inter-subject heterogeneity of P aeruginosa aerosol colony counts was seen and correlated strongly (r=0.73–0.90) with sputum bacterial loads. Modelling decay of viable P aeruginosa in a clinic room suggested that at the recommended ventilation rate of two air changes per hour almost 50 min were required for 90% to be removed after an infected patient left the room. CONCLUSIONS: Viable P aeruginosa in cough aerosols travel further and last longer than recognised previously, providing additional evidence of airborne transmission between patients with CF.",2014 Aug 17,"['Knibbs, Luke D', 'Johnson, Graham R', 'Kidd, Timothy J', 'Cheney, Joyce', 'Grimwood, Keith', 'Kattenbelt, Jacqueline A', ""O'Rourke, Peter K"", 'Ramsay, Kay A', 'Sly, Peter D', 'Wainwright, Claire E', 'Wood, Michelle E', 'Morawska, Lidia', 'Bell, Scott C']",Thorax,,,True
effcf4c34945a660c3328cead86eeb69e387213d,PMC,Viability of Pseudomonas aeruginosa in cough aerosols generated by persons with cystic fibrosis,http://dx.doi.org/10.1136/thoraxjnl-2014-205213,PMC4112489,24743559,CC BY-NC,"BACKGROUND: Person-to-person transmission of respiratory pathogens, including Pseudomonas aeruginosa, is a challenge facing many cystic fibrosis (CF) centres. Viable P aeruginosa are contained in aerosols produced during coughing, raising the possibility of airborne transmission. METHODS: Using purpose-built equipment, we measured viable P aeruginosa in cough aerosols at 1, 2 and 4 m from the subject (distance) and after allowing aerosols to age for 5, 15 and 45 min in a slowly rotating drum to minimise gravitational settling and inertial impaction (duration). Aerosol particles were captured and sized employing an Anderson Impactor and cultured using conventional microbiology. Sputum was also cultured and lung function and respiratory muscle strength measured. RESULTS: Nineteen patients with CF, mean age 25.8 (SD 9.2) years, chronically infected with P aeruginosa, and 10 healthy controls, 26.5 (8.7) years, participated. Viable P aeruginosa were detected in cough aerosols from all patients with CF, but not from controls; travelling 4 m in 17/18 (94%) and persisting for 45 min in 14/18 (78%) of the CF group. Marked inter-subject heterogeneity of P aeruginosa aerosol colony counts was seen and correlated strongly (r=0.73–0.90) with sputum bacterial loads. Modelling decay of viable P aeruginosa in a clinic room suggested that at the recommended ventilation rate of two air changes per hour almost 50 min were required for 90% to be removed after an infected patient left the room. CONCLUSIONS: Viable P aeruginosa in cough aerosols travel further and last longer than recognised previously, providing additional evidence of airborne transmission between patients with CF.",2014 Aug 17,"['Knibbs, Luke D', 'Johnson, Graham R', 'Kidd, Timothy J', 'Cheney, Joyce', 'Grimwood, Keith', 'Kattenbelt, Jacqueline A', ""O'Rourke, Peter K"", 'Ramsay, Kay A', 'Sly, Peter D', 'Wainwright, Claire E', 'Wood, Michelle E', 'Morawska, Lidia', 'Bell, Scott C']",Thorax,,,True
67a530bb1b7075edffe904df66644b0a1da97d1f,PMC,Evaluation of the Temporal Association between Kawasaki Disease and Viral Infections in South Korea,http://dx.doi.org/10.4070/kcj.2014.44.4.250,PMC4117846,25089137,CC BY-NC,"BACKGROUND AND OBJECTIVES: This study is aimed at elucidating potential temporal associations between the occurrence of Kawasaki disease (KD) and various viral infections. SUBJECTS AND METHODS: We obtained monthly patterns of KD from the seventh nationwide survey and viral detection data from the Korea Centers for Disease Control and Prevention from 2009 to 2011 and evaluated temporal correlations between them for each month. The respiratory viruses detected using a multiplex real-time-polymerase chain reaction kit were influenza virus (A/H1N1, A/H3N2, A/H5N1, and B), adenovirus, parainfluenza virus (type 1, 2, 3), respiratory syncytial virus (type A, B), human rhinovirus, human coronavirus (OC43/229E, NL63), human bocavirus, and enterovirus. RESULTS: We obtained data from a total of 13031 patients who were treated for acute KD from 87 hospitals with pediatric residence programs. During this survey, KD showed highest overall incidence in summer and winter seasons and lowest incidence in February and October. We received viral detection data for a total of 14267 patients. Viral detection was highest during winter and spring seasons. The most commonly detected virus was human rhinovirus (32.6%), followed by influenza virus (26.8%). The monthly incidence of KD showed significant correlation with the monthly overall viral detection (p=0.022, r=0.382). In particular, human bocavirus and enterovirus have significant correlations with monthly patterns of KD occurrence (p=0.032 and p=0.007, respectively) and influenza virus correlated with KD occurrence with borderline significance (p=0.063). CONCLUSION: The temporal association between monthly occurrence of KD and viral detection suggests the etiologic importance of precedent infection in the development of KD.",2014 Jul 25,"['Kim, Gi Beom', 'Park, Sohee', 'Kwon, Bo Sang', 'Han, Ji Whan', 'Park, Yong Won', 'Hong, Young Mi']",Korean Circ J,,,True
8f0e032bd15bab3c9c9af33305a2578b525e224c,PMC,Detection of the Middle East Respiratory Syndrome Coronavirus Genome in an Air Sample Originating from a Camel Barn Owned by an Infected Patient,http://dx.doi.org/10.1128/mBio.01450-14,PMC4120199,25053787,CC BY-NC-SA,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel betacoronavirus that has been circulating in the Arabian Peninsula since 2012 and causing severe respiratory infections in humans. While bats were suggested to be involved in human MERS-CoV infections, a direct link between bats and MERS-CoV is uncertain. On the other hand, serological and virological data suggest dromedary camels as the potential animal reservoirs of MERS-CoV. Recently, we isolated MERS-CoV from a camel and its infected owner and provided evidence for the direct transmission of MERS-CoV from the infected camel to the patient. Here, we extend this work and show that identical MERS-CoV RNA fragments were detected in an air sample collected from the same barn that sheltered the infected camel in our previous study. These data indicate that the virus was circulating in this farm concurrently with its detection in the camel and in the patient, which warrants further investigations for the possible airborne transmission of MERS-CoV.",2014 Jul 22,"['Azhar, Esam I.', 'Hashem, Anwar M.', 'El-Kafrawy, Sherif A.', 'Sohrab, Sayed Sartaj', 'Aburizaiza, Asad S.', 'Farraj, Suha A.', 'Hassan, Ahmed M.', 'Al-Saeed, Muneera S.', 'Jamjoom, Ghazi A.', 'Madani, Tariq A.']",mBio,,,True
78c7e03e11c476a3f3f86ace90923131d1e20ba8,PMC,Detection of the Middle East Respiratory Syndrome Coronavirus Genome in an Air Sample Originating from a Camel Barn Owned by an Infected Patient,http://dx.doi.org/10.1128/mBio.01450-14,PMC4120199,25053787,CC BY-NC-SA,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel betacoronavirus that has been circulating in the Arabian Peninsula since 2012 and causing severe respiratory infections in humans. While bats were suggested to be involved in human MERS-CoV infections, a direct link between bats and MERS-CoV is uncertain. On the other hand, serological and virological data suggest dromedary camels as the potential animal reservoirs of MERS-CoV. Recently, we isolated MERS-CoV from a camel and its infected owner and provided evidence for the direct transmission of MERS-CoV from the infected camel to the patient. Here, we extend this work and show that identical MERS-CoV RNA fragments were detected in an air sample collected from the same barn that sheltered the infected camel in our previous study. These data indicate that the virus was circulating in this farm concurrently with its detection in the camel and in the patient, which warrants further investigations for the possible airborne transmission of MERS-CoV.",2014 Jul 22,"['Azhar, Esam I.', 'Hashem, Anwar M.', 'El-Kafrawy, Sherif A.', 'Sohrab, Sayed Sartaj', 'Aburizaiza, Asad S.', 'Farraj, Suha A.', 'Hassan, Ahmed M.', 'Al-Saeed, Muneera S.', 'Jamjoom, Ghazi A.', 'Madani, Tariq A.']",mBio,,,False
04b08eea6a3de3c5eb04509bc1fc47fa9558b8a2,PMC,Detection of the Middle East Respiratory Syndrome Coronavirus Genome in an Air Sample Originating from a Camel Barn Owned by an Infected Patient,http://dx.doi.org/10.1128/mBio.01450-14,PMC4120199,25053787,CC BY-NC-SA,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel betacoronavirus that has been circulating in the Arabian Peninsula since 2012 and causing severe respiratory infections in humans. While bats were suggested to be involved in human MERS-CoV infections, a direct link between bats and MERS-CoV is uncertain. On the other hand, serological and virological data suggest dromedary camels as the potential animal reservoirs of MERS-CoV. Recently, we isolated MERS-CoV from a camel and its infected owner and provided evidence for the direct transmission of MERS-CoV from the infected camel to the patient. Here, we extend this work and show that identical MERS-CoV RNA fragments were detected in an air sample collected from the same barn that sheltered the infected camel in our previous study. These data indicate that the virus was circulating in this farm concurrently with its detection in the camel and in the patient, which warrants further investigations for the possible airborne transmission of MERS-CoV.",2014 Jul 22,"['Azhar, Esam I.', 'Hashem, Anwar M.', 'El-Kafrawy, Sherif A.', 'Sohrab, Sayed Sartaj', 'Aburizaiza, Asad S.', 'Farraj, Suha A.', 'Hassan, Ahmed M.', 'Al-Saeed, Muneera S.', 'Jamjoom, Ghazi A.', 'Madani, Tariq A.']",mBio,,,False
0f8f7f09b42b4b45e128591191176aa358f29b1b,PMC,"Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3",http://dx.doi.org/10.1038/srep06006,PMC4126003,25103253,CC BY-NC-ND,"As a prompt response against invasion of various viruses, interferon regulatory factor-3 (IRF-3) is initially phosphorylated to become activated and upregulates mainly Type I Interferons (IFN-I) in most cell types. We previously reported that IRF-3-dependent host innate immune responses partially interfere in infection of prions. Here, we found that stable infection of prion suppressed IRF-3 gene-expression. The decreased promoter activity of IRF-3 was significantly restored along with treatment of anti-prion drugs in the prion-infected cells, suggesting that infection of prion directly influence the regulation of IRF-3 transcription. We further investigated promoter activity of 5′- flanking region of murine IRF-3 using a luciferase reporter system and found that the nucleotides -119 to -1 were indispensable for the promoter activity. Within this region, mutations in the Oct-1 binding site significantly reduced the promoter activity and chromatin immunoprecipitation (ChIP) assay revealed that Oct-1 indeed binds to the region. In addition, overexpression of Oct-1 increased the promoter activity of IRF-3. Intriguingly, Oct-1 protein was significantly reduced in prion-infected cells and mice brains compared with uninfected groups. Taken together, we concluded that prion infection could interfere in the function of Oct-1, resulting in the down-regulation of IRF-3.",2014 Aug 8,"['Homma, Takujiro', 'Ishibashi, Daisuke', 'Nakagaki, Takehiro', 'Fuse, Takayuki', 'Sano, Kazunori', 'Satoh, Katsuya', 'Atarashi, Ryuichiro', 'Nishida, Noriyuki']",Sci Rep,,,True
289ec6df74861187e1a406b2fe0cae2e3b8e370f,PMC,"Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3",http://dx.doi.org/10.1038/srep06006,PMC4126003,25103253,CC BY-NC-ND,"As a prompt response against invasion of various viruses, interferon regulatory factor-3 (IRF-3) is initially phosphorylated to become activated and upregulates mainly Type I Interferons (IFN-I) in most cell types. We previously reported that IRF-3-dependent host innate immune responses partially interfere in infection of prions. Here, we found that stable infection of prion suppressed IRF-3 gene-expression. The decreased promoter activity of IRF-3 was significantly restored along with treatment of anti-prion drugs in the prion-infected cells, suggesting that infection of prion directly influence the regulation of IRF-3 transcription. We further investigated promoter activity of 5′- flanking region of murine IRF-3 using a luciferase reporter system and found that the nucleotides -119 to -1 were indispensable for the promoter activity. Within this region, mutations in the Oct-1 binding site significantly reduced the promoter activity and chromatin immunoprecipitation (ChIP) assay revealed that Oct-1 indeed binds to the region. In addition, overexpression of Oct-1 increased the promoter activity of IRF-3. Intriguingly, Oct-1 protein was significantly reduced in prion-infected cells and mice brains compared with uninfected groups. Taken together, we concluded that prion infection could interfere in the function of Oct-1, resulting in the down-regulation of IRF-3.",2014 Aug 8,"['Homma, Takujiro', 'Ishibashi, Daisuke', 'Nakagaki, Takehiro', 'Fuse, Takayuki', 'Sano, Kazunori', 'Satoh, Katsuya', 'Atarashi, Ryuichiro', 'Nishida, Noriyuki']",Sci Rep,,,False
934f45d3ce46b7e090b1a3d76a96e2acb705cc91,PMC,"Coronaviruses Induce Entry-Independent, Continuous Macropinocytosis",http://dx.doi.org/10.1128/mBio.01340-14,PMC4128357,25096879,CC BY-NC-SA,"Macropinocytosis is exploited by many pathogens for entry into cells. Coronaviruses (CoVs) such as severe acute respiratory syndrome (SARS) CoV and Middle East respiratory syndrome CoV are important human pathogens; however, macropinocytosis during CoV infection has not been investigated. We demonstrate that the CoVs SARS CoV and murine hepatitis virus (MHV) induce macropinocytosis, which occurs late during infection, is continuous, and is not associated with virus entry. MHV-induced macropinocytosis results in vesicle internalization, as well as extended filopodia capable of fusing with distant cells. MHV-induced macropinocytosis requires fusogenic spike protein on the cell surface and is dependent on epidermal growth factor receptor activation. Inhibition of macropinocytosis reduces supernatant viral titers and syncytia but not intracellular virus titers. These results indicate that macropinocytosis likely facilitates CoV infection through enhanced cell-to-cell spreading. Our studies are the first to demonstrate virus use of macropinocytosis for a role other than entry and suggest a much broader potential exploitation of macropinocytosis in virus replication and host interactions.",2014 Aug 5,"['Freeman, Megan Culler', 'Peek, Christopher T.', 'Becker, Michelle M.', 'Smith, Everett Clinton', 'Denison, Mark R.']",mBio,,,True
be2d158bbbfa93b845e21ad069c6694de4ff7c7a,PMC,"Risks and Benefits of Gain-of-Function Experiments with Pathogens of Pandemic Potential, Such as Influenza Virus: a Call for a Science-Based Discussion",http://dx.doi.org/10.1128/mBio.01730-14,PMC4128368,25085113,CC BY-NC-SA,,2014 Aug 1,"['Casadevall, Arturo', 'Imperiale, Michael J.']",mBio,,,True
2285bbcea934e093b35c23152a3314aab4969ddd,PMC,The potential contributions of traditional Chinese medicine to emergency medicine,http://dx.doi.org/10.5847/wjem.j.issn.1920-8642.2013.02.002,PMC4129829,25215100,CC BY-NC-SA,"BACKGROUND: Despite the fact that traditional Chinese medicine (TCM) has been developed and used to treat acute and urgent illness for many thousands of years. TCM has been widely perceived in western societies that TCM may only be effective to treat chronic diseases. The aim of this article is to provide some scientific evidence regarding the application of TCM in emergency medicine and its future potential. METHODS: Multiple databases (PubMed, ProQuest, Academic Search Elite and Science Direct) were searched using the terms: Traditional Chinese Medicine/ Chinese Medicine, Emergency Medicine, China. In addition, three leading TCM Journals in China were searched via Oriprobe Information Services for relevant articles (published from 1990—2012). Particular attention was paid to those articles that are related to TCM treatments or combined medicine in dealing with intensive and critical care. RESULTS: TCM is a systematic traditional macro medicine. The clinical practice of TCM is guided by the TCM theoretical framework – a methodology founded thousands of years ago. As the methodologies between TCM and Biomedicine are significantly different, it provides an opportunity to combine two medicines, in order to achieve clinical efficacy. Nowadays, combined medicine has become a common clinical model particular in TCM hospitals in China. CONCLUSIONS: It is evident that TCM can provide some assistance in emergency although to combine them in practice is still its infant form and is mainly at TCM hospitals in China. The future effort could be put into TCM research, both in laboratories and clinics, with high quality designs, so that TCM could be better understood and then applied in emergency medicine.",2013,"['He, Jun', 'Hou, Xiang-yu']",World J Emerg Med,,,True
c2263b536f0cdd99a4e09e96859c007d44cef013,PMC,Immunomodulatory Effects of Kimchi in Chinese Healthy College Students: A Randomized Controlled Trial,http://dx.doi.org/10.7762/cnr.2014.3.2.98,PMC4135247,25136537,CC BY-NC,"This study examined the potential immunomodulatory effects of Kimchi, a traditional fermented Korean vegetable, in healthy Chinese college students. The four-week clinical-trial (randomized, open-label, prospective, controlled) was followed by a one week wash-out period. Healthy Chinese college students (over 20 years of age with a body mass index of 18.5-23.0 kg/m(2)) volunteered for this study. Forty-three students were randomly classified into two groups, Kimchi (n = 21, supplemented with 100 g of Kimchi per day) or non-Kimchi (n = 22, supplemented with 100 g of radish per day, control) groups. During the four-week intervention period, students were asked to maintain their usual diet and activity, and instructed not to take any medications, functional food products, or dietary supplements. Anthropometrics, nutritional intake, and blood immune parameters (lymphocyte subsets, cytokines, and immunoglobulins) were measured before and after the four weeks of intervention. Thirty-nine students (19 in the Kimchi group, 20 in the non-Kimchi group) finished the study. After the intervention, no significant changes were observed in lymphocyte subsets (T-cell, B-cell, NK cell), pro-inflammatory cytokines (IL-6, TNF-α), anti-inflammatory cytokines (IL-4 and IL-10), and immunoglobulins (Ig A, G, and M) between groups in either the Kimchi or non-Kimchi. These results suggest that the short-term consumption of Kimchi has no immunomodulatory effects in healthy Chinese college students.",2014 Jul 29,"['Lee, Hansongyi', 'Kim, Do Yeon', 'Lee, Mi Ae', 'Jang, Ja-Young', 'Choue, Ryowon']",Clin Nutr Res,,,True
830267d850fecba497f80f0c51331a397a734a94,PMC,Middle East respiratory syndrome (MERS): A new zoonotic viral pneumonia,http://dx.doi.org/10.4161/viru.32077,PMC4139405,25089913,CC BY-NC,"Coronaviruses have traditionally been associated with mild upper respiratory tract infections throughout the world. In the fall of 2002, a new coronavirus emerged in in Asia causing severe viral pneumonia, i.e., severe acute respiratory syndrome (SARS). Nearly a decade following the SARS epidemic, a new coronavirus causing severe viral pneumonia has emerged, i.e., middle east respiratory syndrome (MERS). Since the initial case of MERS-CoV occurred in June of 2012 in Saudi Arabia there have been 688 confirmed cases and 282 deaths in 20 countries.   Although both SARS and MERS are caused by coronaviruses, SARS was characterized by efficient human transmission and relatively low mortality rate. In contrast, MERS is relatively inefficiently transmitted to humans but has a high mortality rate. Given the potential overlap in presentation and manifestation, it is important to understand the clinical and epidemiologic differences between MERS, SARS and influenza.",2014 Aug 15,"['Cunha, Cheston B', 'Opal, Steven M']",Virulence,,,True
d212d002cb2b3bd66d6633aea1cc8c816be9c114,PMC,Drugs in upper respiratory tract infections in paediatric patients in North Trinidad,,PMC4139753,25147589,CC BY-NC-SA,"OBJECTIVE: We explored the prescribing patterns of physicians in North Trinidad in treating upper respiratory tract infections (URTI) in paediatric patients and the appropriateness of drugs prescribed. METHODS: A retrospective observational study was conducted, with a sample size of 523 paediatric patients, diagnosed with an URTI during the period of June 2003 to 22 June 2005. The study was conducted at five Primary Health Care Facilities in North Trinidad. RESULTS: The three most frequent URTIs diagnosed were non-specific URTI, common cold, and acute tonsillitis in rank order. Four patterns of prescribing were identified, (1) no drug therapy [1.9%]; (2) antibiotic therapy alone [6.1%]; (3) antibiotic and symptomatic therapy [53.0%]; and (4) symptomatic therapy alone [39.0%]. The, most frequently prescribed antibiotics were penicillins (amoxicillin [46.3%] and amoxicillin/clavulanate [5.3%]) and a macrolide (erythromycin [6.1%]). The three symptomatic agents most frequently prescribed were paracetamol [40.1%]; diphenhydramine [29.1%]; and normal saline nasal drops [14.2%]. In 112 cases with swab analyses done, of these, 98.2% revealed a growth of commensals only, while 1.8% grew pathogenic micro-organisms. Of the cases showing commensal growth only, 84.6% were treated with an antibiotic, 14.5% were treated with symptomatic agents alone and 0.9% received no drug therapy at all. CONCLUSIONS: A large proportion of paediatric patients diagnosed with an URTI in North Trinidad was prescribed antibiotics although not indicated The inappropriate use of antibiotics can potentiate the worldwide trend of antimicrobial resistance.",2009 Mar 15 Jan-Mar,"['Mungrue, Kameel', 'Brown, Tessa', 'Hayes, Ivory', 'Ramroop, Savatri', 'Thurston, Portio', 'Pereira, Lexley PINTO']",Pharm Pract (Granada),,,True
358ab81c15c1c24b69c02cfa8cf52069a7e2932b,PMC,Mining Social Media and Web Searches For Disease Detection,http://dx.doi.org/10.4081/jphr.2013.e4,PMC4140326,25170475,CC BY-NC,"Web-based social media is increasingly being used across different settings in the health care industry. The increased frequency in the use of the Internet via computer or mobile devices provides an opportunity for social media to be the medium through which people can be provided with valuable health information quickly and directly. While traditional methods of detection relied predominately on hierarchical or bureaucratic lines of communication, these often failed to yield timely and accurate epidemiological intelligence. New web-based platforms promise increased opportunities for a more timely and accurate spreading of information and analysis. This article aims to provide an overview and discussion of the availability of timely and accurate information. It is especially useful for the rapid identification of an outbreak of an infectious disease that is necessary to promptly and effectively develop public health responses. These web-based platforms include search queries, data mining of web and social media, process and analysis of blogs containing epidemic key words, text mining, and geographical information system data analyses. These new sources of analysis and information are intended to complement traditional sources of epidemic intelligence. Despite the attractiveness of these new approaches, further study is needed to determine the accuracy of blogger statements, as increases in public participation may not necessarily mean the information provided is more accurate.",2013 May 31,"['Yang, Y. Tony', 'Horneffer, Michael', 'DiLisio, Nicole']",J Public Health Res,,,True
ff2ac3737c6edf81ff29b8d72c3abc2b3df5b344,PMC,Current perspectives in transfusion-transmitted infectious diseases: emerging and re-emerging infections,http://dx.doi.org/10.1111/voxs.12070,PMC4142007,25210533,CC BY-NC-ND,"BACKGROUND: In August 2009, a group from the AABB (Stramer et al., Transfusion 2009;99:1S–29S, Emerging Infectious Disease Agents and their Potential Threat to Transfusion Safety; http://www.aabb.org/resources/bct/eid/Pages/default.aspx) published a Supplement to Transfusion that reviewed emerging infectious disease (EID) agents that pose a real or theoretical threat to transfusion safety, but for which an existing effective intervention is lacking. The necessary attributes for transfusion transmission were outlined including: presence of the agent in blood during the donor's asymptomatic phase, the agent's survival/persistence in blood during processing/storage, and lastly that the agent must be recognized as responsible for a clinically apparent outcome in at least a proportion of recipients who become infected. Without these attributes, agents are not considered as a transfusion-transmission threat and were excluded. Sixty-eight such agents were identified with enough evidence/likelihood of transfusion transmission (e.g., blood phase) and potential for clinical disease to warrant further consideration. In the Supplement, Fact Sheets (FS) were published providing information on: agent classification; disease agent's importance; clinical syndromes/diseases caused; transmission modes (including vectors/reservoirs); likelihood of transfusion transmission, and if proven to be transfusion-transmitted, information on known cases; the feasibility/predicted success of interventions for donor screening (questioning) and tests available for diagnostics/ adapted for donor screening; and finally, the efficacy, if known, of inactivation methods for plasma-derived products. The Supplement included a separate section on pathogen reduction using published data. Agents were prioritized relative to their scientific/epidemiologic threat and their perceived threat to the community including concerns expressed by the regulators of blood. Agents given the highest priority due to a known transfusion-transmission threat and severe/fatal disease in recipients were the vCJD prion, dengue viruses and the obligate red-cell parasite that causes babesiosis (B. microti and related Babesia). Although the focus of the Supplement was towards the United States and Canada, many of the agents (and the process) are applicable worldwide. NEXT STEPS: Since the publication of the Supplement, six new FSs (yellow fever viruses-including vaccine breakthrough infections, miscellaneous arboviruses, XMRV, human parvoviruses/bocaviruses other than B19, and most recently the Middle East respiratory syndrome coronavirus, MERS-CoV) were added and 14 existing FSs updated (Anaplasma, Babesia, Bartonella, Erhlichia, chronic wasting disease-CWD, human prions other than vCJD, vCJD, Coxiella burnetii-the agent of Q fever, dengue viruses, HAV, HEV, Japanese encephalitis-JE complex, tick-borne encephalitis viruses-TBEV, and human parvovirus B19). Also, tables were released outlining pathogen reduction clinical trials/results (published) and availability/commercial routine use of such technologies by country. Of necessity, the list of EID agents is not, and can never be, complete due to the nature of emergence. We recognized that a system of assessing the risk/threat of EIDs for their potential impact on blood safety and availability must include processes for monitoring, identifying, evaluating, estimating severity, assessing risk and developing interventions. Thus, a ‘toolkit’ containing the necessary ‘tools’ from EID monitoring (horizon scanning) to validation/effectiveness evaluations of interventions is being developed. The goal is, to develop a systematic approach to risk assessment and intervention development for the impact of emerging infectious upon blood safety intended to educate and provide advise about risks/interventions in a timely/accurate fashion. CONCLUSIONS: The process and final product (toolkit) including methods to monitor EID agent emergence, identification/recognition of a transfusion-transmission threat, methods for quantitative risk assessments, and the appropriate management of such threats should be considered for implementation by all blood systems.",2014 Jul 28,"Stramer, S L",ISBT Sci Ser,,,True
7f7c8429d7011635b8f8a3415e6ace00c2bf4df0,PMC,Parasite and viral species richness of Southeast Asian bats: Fragmentation of area distribution matters,http://dx.doi.org/10.1016/j.ijppaw.2014.06.003,PMC4142259,25161915,CC BY-NC-ND,"Interest in bat-borne diseases and parasites has grown in the past decade over concerns for human health. However, the drivers of parasite diversity among bat host species are understudied as are the links between parasite richness and emerging risks. Thus, we aimed at exploring factors that explain macro and microparasite species richness in bats from Southeast Asia, a hotspot of emerging infectious diseases. First, we identified bat species that need increased sampling effort for pathogen discovery. Our approach highlights pathogen investigation disparities among species within the same genus, such as Rhinolophus and Pteropus. Secondly, comparative analysis using independent contrasts method allowed the identification of likely factors explaining parasite and viral diversity of bats. Our results showed a key role of bat distribution shape, an index of the fragmentation of bat distribution, on parasite diversity, linked to a decrease for both viral and endoparasite species richness. We discuss how our study may contribute to a better understanding of the link between parasite species richness and emergence.",2014 Jul 8,"['Gay, Noellie', 'Olival, Kevin J.', 'Bumrungsri, Sara', 'Siriaroonrat, Boripat', 'Bourgarel, Mathieu', 'Morand, Serge']",Int J Parasitol Parasites Wildl,,,False
41df61dc89201d699b23532cbd09da787afa7e84,PMC,ERKs and mitochondria-related pathways are essential for glycyrrhizic acid-mediated neuroprotection against glutamate-induced toxicity in differentiated PC12 cells,http://dx.doi.org/10.1590/1414-431X20143760,PMC4143205,25075574,CC BY-NC,"The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA, a major compound separated from Glycyrrhiza Radix, which is a crude Chinese traditional drug) against glutamate-induced cytotoxicity in differentiated PC12 (DPC12) cells. The results showed that GA treatment improved cell viability and ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12 cells. GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited glutamate-enhanced expressions of Bax and cleaved caspase 3, and reduced cytochrome C (Cyto C) release. Exposure to glutamate strongly inhibited phosphorylation of AKT (protein kinase B) and extracellular signal-regulated kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT. The presence of PD98059 (a mitogen-activated protein/extracellular signal-regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3-kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of glutamate-exposed DPC12 cells. These results indicated that ERKs and mitochondria-related pathways are essential for the neuroprotective effect of GA against glutamate-induced toxicity in DPC12 cells. The present study provides experimental evidence supporting GA as a potential therapeutic agent for use in the treatment of neurodegenerative diseases.",2014 Jul 25,"['Wang, D.', 'Guo, T.Q.', 'Wang, Z.Y.', 'Lu, J.H.', 'Liu, D.P.', 'Meng, Q.F.', 'Xie, J.', 'Zhang, X.L.', 'Liu, Y.', 'Teng, L.S.']",Braz J Med Biol Res,,,True
cb5a49679732abf852dec6e61e435602706289c3,PMC,Influenza Virus A/Anhui/1/2013 (H7N9) Replicates Efficiently in the Upper and Lower Respiratory Tracts of Cynomolgus Macaques,http://dx.doi.org/10.1128/mBio.01331-14,PMC4145683,25118237,CC BY-NC-SA,"In March 2013, three fatal human cases of infection with influenza A virus (H7N9) were reported in China. Since then, human cases have been accumulating. Given the public health importance of this virus, we performed a pathogenicity study of the H7N9 virus in the cynomolgus macaque model, focusing on clinical aspects of disease, radiographic, histological, and gene expression profile changes in the upper and lower respiratory tracts, and changes in systemic cytokine and chemokine profiles during infection. Cynomolgus macaques developed transient, mild to severe disease with radiographic evidence of pulmonary infiltration. Virus replicated in the upper as well as lower respiratory tract, with sustained replication in the upper respiratory tract until the end of the experiment at 6 days after inoculation. Virus shedding occurred mainly via the throat. Histopathological changes in the lungs were similar to those observed in humans, albeit less severe, with diffuse alveolar damage, infiltration of polymorphonuclear cells, formation of hyaline membranes, pneumocyte hyperplasia, and fibroproliferative changes. Analysis of gene expression profiles in lung lesions identified pathways involved in tissue damage during H7N9 infection as well as leads for development of therapeutics targeting host responses rather than virus replication. Overall, H7N9 infection was not as severe in cynomolgus macaques as in humans, supporting the possible role of underlying medical complications in disease severity as discussed for human H7N9 infection (H. N. Gao et al., N. Engl. J. Med. 368:2277–2285, 2013, doi:10.1056/NEJMoa1305584).",2014 Aug 12,"['de Wit, Emmie', 'Rasmussen, Angela L.', 'Feldmann, Friederike', 'Bushmaker, Trenton', 'Martellaro, Cynthia', 'Haddock, Elaine', 'Okumura, Atsushi', 'Proll, Sean C.', 'Chang, Jean', 'Gardner, Don', 'Katze, Michael G.', 'Munster, Vincent J.', 'Feldmann, Heinz']",mBio,,,True
a1a42c57944364ac541ff7ea1c0a545c2edabcac,PMC,Influenza Virus A/Anhui/1/2013 (H7N9) Replicates Efficiently in the Upper and Lower Respiratory Tracts of Cynomolgus Macaques,http://dx.doi.org/10.1128/mBio.01331-14,PMC4145683,25118237,CC BY-NC-SA,"In March 2013, three fatal human cases of infection with influenza A virus (H7N9) were reported in China. Since then, human cases have been accumulating. Given the public health importance of this virus, we performed a pathogenicity study of the H7N9 virus in the cynomolgus macaque model, focusing on clinical aspects of disease, radiographic, histological, and gene expression profile changes in the upper and lower respiratory tracts, and changes in systemic cytokine and chemokine profiles during infection. Cynomolgus macaques developed transient, mild to severe disease with radiographic evidence of pulmonary infiltration. Virus replicated in the upper as well as lower respiratory tract, with sustained replication in the upper respiratory tract until the end of the experiment at 6 days after inoculation. Virus shedding occurred mainly via the throat. Histopathological changes in the lungs were similar to those observed in humans, albeit less severe, with diffuse alveolar damage, infiltration of polymorphonuclear cells, formation of hyaline membranes, pneumocyte hyperplasia, and fibroproliferative changes. Analysis of gene expression profiles in lung lesions identified pathways involved in tissue damage during H7N9 infection as well as leads for development of therapeutics targeting host responses rather than virus replication. Overall, H7N9 infection was not as severe in cynomolgus macaques as in humans, supporting the possible role of underlying medical complications in disease severity as discussed for human H7N9 infection (H. N. Gao et al., N. Engl. J. Med. 368:2277–2285, 2013, doi:10.1056/NEJMoa1305584).",2014 Aug 12,"['de Wit, Emmie', 'Rasmussen, Angela L.', 'Feldmann, Friederike', 'Bushmaker, Trenton', 'Martellaro, Cynthia', 'Haddock, Elaine', 'Okumura, Atsushi', 'Proll, Sean C.', 'Chang, Jean', 'Gardner, Don', 'Katze, Michael G.', 'Munster, Vincent J.', 'Feldmann, Heinz']",mBio,,,False
734f6b97fbdf729498fe7077f74f49db8311d2b9,PMC,The pattern of Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive epidemiological analysis of data from the Saudi Ministry of Health,http://dx.doi.org/10.2147/IJGM.S67061,PMC4149400,25187734,CC BY-NC,"PURPOSE: This study describes the epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia. PATIENTS AND METHODS: Epidemiological analysis was performed on data from all MERS-CoV cases recorded by the Saudi Ministry of Health between June 6, 2013 and May 14, 2014. The frequency of cases and deaths was calculated and adjusted by month, sex, age group, and region. The average monthly temperature and humidity of infected regions throughout the year was also calculated. RESULTS: A total of 425 cases were recorded over the study period. The highest number of cases and deaths occurred between April and May 2014. Disease occurrence among men (260 cases [62%]) was higher than in women (162 cases [38%]), and the case fatality rate was higher for men (52%) than for women (23%). In addition, those in the 45–59 years and ≥60 years age groups were most likely to be infected, and the case fatality rate for these people was higher than for other groups. The highest number of cases and deaths were reported in Riyadh (169 cases; 43 deaths), followed by Jeddah (156 cases; 36 deaths) and the Eastern Region (24 cases; 22 deaths). The highest case fatality rate was in the Eastern Region (92%), followed by Medinah (36%) and Najran (33%). MERS-CoV infection actively causes disease in environments with low relative humidity (<20%) and high temperature (15°C–35°C). CONCLUSION: MERS-CoV is considered an epidemic in Saudi Arabia. The frequency of cases and deaths is higher among men than women, and those above 45 years of age are most affected. Low relative humidity and high temperature can enhance the spread of this disease in the entire population. Further analytical studies are required to determine the source and mode of infection in Saudi Arabia.",2014 Aug 20,"['Alghamdi, Ibrahim G', 'Hussain, Issam I', 'Almalki, Shaia S', 'Alghamdi, Mohamed S', 'Alghamdi, Mansour M', 'El-Sheemy, Mohammed A']",Int J Gen Med,,,True
a10f6c3dce3d0abbf575b64df42348446c105b57,PMC,Design of an epitope-based peptide vaccine against spike protein of human coronavirus: an in silico approach,http://dx.doi.org/10.2147/DDDT.S67861,PMC4149408,25187696,CC BY-NC,"Human coronavirus (HCoV), a member of Coronaviridae family, is the causative agent of upper respiratory tract infections and “atypical pneumonia”. Despite severe epidemic outbreaks on several occasions and lack of antiviral drug, not much progress has been made with regard to an epitope-based vaccine designed for HCoV. In this study, a computational approach was adopted to identify a multiepitope vaccine candidate against this virus that could be suitable to trigger a significant immune response. Sequences of the spike proteins were collected from a protein database and analyzed with an in silico tool, to identify the most immunogenic protein. Both T cell immunity and B cell immunity were checked for the peptides to ensure that they had the capacity to induce both humoral and cell-mediated immunity. The peptide sequence from 88–94 amino acids and the sequence KSSTGFVYF were found as the most potential B cell and T cell epitopes, respectively. Furthermore, conservancy analysis was also done using in silico tools and showed a conservancy of 64.29% for all epitopes. The peptide sequence could interact with as many as 16 human leukocyte antigens (HLAs) and showed high cumulative population coverage, ranging from 75.68% to 90.73%. The epitope was further tested for binding against the HLA molecules, using in silico docking techniques, to verify the binding cleft epitope interaction. The allergenicity of the epitopes was also evaluated. This computational study of design of an epitope-based peptide vaccine against HCoVs allows us to determine novel peptide antigen targets in spike proteins on intuitive grounds, albeit the preliminary results thereof require validation by in vitro and in vivo experiments.",2014 Aug 21,"['Oany, Arafat Rahman', 'Emran, Abdullah-Al', 'Jyoti, Tahmina Pervin']",Drug Des Devel Ther,,,True
756dbc931627ce595e70224e084e8cb89d38287c,PMC,Effect of integrated traditional Chinese medicine and western medicine on the treatment of severe acute respiratory syndrome: A meta-analysis,,PMC4155143,25214911,CC BY-NC-SA,"BACKGROUND: Data regarding the treatment efficacy of integrative treatment of Traditional Chinese Medicine (TCM) and Western Medicine (WM) in treating patients with (SARS) are conflicting. The effects of integrative TCM/WM treatment have not been fully quantified. OBJECTIVES: To systematically asses the treatment effects of integrated TCM with WM versus WM alone in patients with SARS, incorporating data from recently published studies. METHODS: A meta-analysis was conducted, using published randomized and nonrandomized controlled clinical studies that compared the treatment effects of integrative TCM/WM with WM alone from 2002 to 2006. The outcome measurements included mortality rate, cure rate, resolution of pulmonary infiltrate, use of corticosteroid, and time to defervescence. The effect sizes were presented as risk ratio (RR), rate difference (RD), and weighted mean difference (WMD). The pooled effect sizes were calculated by both fixed-effects and random-effects models. RESULTS: A total of 1,678 patients with a diagnosis of SARS were identified, including 866 patients from 16 randomized controlled studies and 812 patients from 8 nonrandomized controlled studies. There were no differences detected in mortality rate or cure rate between treatments. Compared with patients receiving WM treatment alone, patients receiving integrative treatment were more likely to have complete or partial resolution of pulmonary infiltrate (RD=0.18, 95%CI; 0.07 to 0.30), lower average daily dosage (mg) of corticosteroid (WMD=-60.27, 95% CI; -70.58 to -49.96), higher CD4+ counts (cells/uL) (WMD=167.96, 95% CI; 109.68 to 226.24), and shorter time to defervescence (days) (WMD= -1.06, 95%CI;-1.60 to -0.53). CONCLUSIONS: The experience of integrative TCM/WM in the treatment of SARS is encouraging. The use of TCM as an adjunctive therapy in the treatment of SARS should be further investigated.",2007 Apr 2 Jan-Mar,"['Chen, Yan', 'Guo, Jeff J.', 'Healy, Daniel P', 'Zhan, Siyan']",Pharm Pract (Granada),,,True
22dce3fab7317bb2a8ff48f0da6f2c9717dc6ed9,PMC,Phylogenetic Analysis of Astrovirus and Kobuvirus in Korean Dogs,http://dx.doi.org/10.1292/jvms.13-0585,PMC4155196,24784439,CC BY-NC-ND,"Astroviruses and kobuviruses are frequently found in mammalian feces, including that of humans. The present study examined fecal samples from 91 Korean dogs suffering from diarrhea. Canine astroviruses (CAstVs) and canine kobuviruses (CKoVs) were identified in 2 (2.1%) and 46 (50.6%) dogs, respectively. Nucleotide sequence analysis coupled with phylogenetic analysis using the neighbor-joining method showed that CAstVs clustered into four genetically diverse groups. Two Korean CAstVs belonged to group 2 alongside strains isolated in Italy and France. Twelve of the Korean CKoVs belonged to a single clade, along with strain UK003 identified in the UK and six CKoVs identified in the USA. Thus, the results suggest that the Korean strain of CAstV is closely related to strains isolated in Europe. Surely, CKoV in South Korea could identify the circulation among dogs population.",2014 Aug 1,"['CHOI, Sarah', 'LIM, Seong-In', 'KIM, Yong Kwan', 'CHO, Yoon-Young', 'SONG, Jae-Young', 'AN, Dong-Jun']",J Vet Med Sci,,,True
5f4261729c0f4fadccac90a0da2c995f13b65802,PMC,"Murine AKAP7 Has a 2′,5′-Phosphodiesterase Domain That Can Complement an Inactive Murine Coronavirus ns2 Gene",http://dx.doi.org/10.1128/mBio.01312-14,PMC4161237,24987090,CC BY-NC-SA,"Viral 2′,5′-phosphodiesterases (2′,5′-PDEs) help disparate RNA viruses evade the antiviral activity of interferon (IFN) by degrading 2′,5′-oligoadenylate (2-5A) activators of RNase L. A kinase anchoring proteins (AKAPs) bind the regulatory subunits of protein kinase A (PKA) to localize and organize cyclic AMP (cAMP) signaling during diverse physiological processes. Among more than 43 AKAP isoforms, AKAP7 appears to be unique in its homology to viral 2′,5′-PDEs. Here we show that mouse AKAP7 rapidly degrades 2-5A with kinetics similar to that of murine coronavirus (mouse hepatitis virus [MHV]) strain A59 ns2 and human rotavirus strain WA VP3 proteins. To determine whether AKAP7 could substitute for a viral 2′,5′-PDE, we inserted AKAP7 cDNA into an MHV genome with an inactivated ns2 gene. The AKAP7 PDE domain or N-terminally truncated AKAP7 (both lacking a nuclear localization motif), but not full-length AKAP7 or a mutant, AKAP7(H185R), PDE domain restored the infectivity of ns2 mutant MHV in bone marrow macrophages and in livers of infected mice. Interestingly, the AKAP7 PDE domain and N-terminally deleted AKAP7 were present in the cytoplasm (the site of MHV replication), whereas full-length AKAP7 was observed only in nuclei. We suggest the possibility that viral acquisition of the host AKAP7 PDE domain might have occurred during evolution, allowing diverse RNA viruses to antagonize the RNase L pathway.",2014 Jul 1,"['Gusho, Elona', 'Zhang, Rong', 'Jha, Babal K.', 'Thornbrough, Joshua M.', 'Dong, Beihua', 'Gaughan, Christina', 'Elliott, Ruth', 'Weiss, Susan R.', 'Silverman, Robert H.']",mBio,,,True
51ff788befbfe296213c744882ef227b601def83,PMC,"Murine AKAP7 Has a 2′,5′-Phosphodiesterase Domain That Can Complement an Inactive Murine Coronavirus ns2 Gene",http://dx.doi.org/10.1128/mBio.01312-14,PMC4161237,24987090,CC BY-NC-SA,"Viral 2′,5′-phosphodiesterases (2′,5′-PDEs) help disparate RNA viruses evade the antiviral activity of interferon (IFN) by degrading 2′,5′-oligoadenylate (2-5A) activators of RNase L. A kinase anchoring proteins (AKAPs) bind the regulatory subunits of protein kinase A (PKA) to localize and organize cyclic AMP (cAMP) signaling during diverse physiological processes. Among more than 43 AKAP isoforms, AKAP7 appears to be unique in its homology to viral 2′,5′-PDEs. Here we show that mouse AKAP7 rapidly degrades 2-5A with kinetics similar to that of murine coronavirus (mouse hepatitis virus [MHV]) strain A59 ns2 and human rotavirus strain WA VP3 proteins. To determine whether AKAP7 could substitute for a viral 2′,5′-PDE, we inserted AKAP7 cDNA into an MHV genome with an inactivated ns2 gene. The AKAP7 PDE domain or N-terminally truncated AKAP7 (both lacking a nuclear localization motif), but not full-length AKAP7 or a mutant, AKAP7(H185R), PDE domain restored the infectivity of ns2 mutant MHV in bone marrow macrophages and in livers of infected mice. Interestingly, the AKAP7 PDE domain and N-terminally deleted AKAP7 were present in the cytoplasm (the site of MHV replication), whereas full-length AKAP7 was observed only in nuclei. We suggest the possibility that viral acquisition of the host AKAP7 PDE domain might have occurred during evolution, allowing diverse RNA viruses to antagonize the RNase L pathway.",2014 Jul 1,"['Gusho, Elona', 'Zhang, Rong', 'Jha, Babal K.', 'Thornbrough, Joshua M.', 'Dong, Beihua', 'Gaughan, Christina', 'Elliott, Ruth', 'Weiss, Susan R.', 'Silverman, Robert H.']",mBio,,,False
a83f14464310d40fdac66e2b2a00355dcf0b4737,PMC,"Murine AKAP7 Has a 2′,5′-Phosphodiesterase Domain That Can Complement an Inactive Murine Coronavirus ns2 Gene",http://dx.doi.org/10.1128/mBio.01312-14,PMC4161237,24987090,CC BY-NC-SA,"Viral 2′,5′-phosphodiesterases (2′,5′-PDEs) help disparate RNA viruses evade the antiviral activity of interferon (IFN) by degrading 2′,5′-oligoadenylate (2-5A) activators of RNase L. A kinase anchoring proteins (AKAPs) bind the regulatory subunits of protein kinase A (PKA) to localize and organize cyclic AMP (cAMP) signaling during diverse physiological processes. Among more than 43 AKAP isoforms, AKAP7 appears to be unique in its homology to viral 2′,5′-PDEs. Here we show that mouse AKAP7 rapidly degrades 2-5A with kinetics similar to that of murine coronavirus (mouse hepatitis virus [MHV]) strain A59 ns2 and human rotavirus strain WA VP3 proteins. To determine whether AKAP7 could substitute for a viral 2′,5′-PDE, we inserted AKAP7 cDNA into an MHV genome with an inactivated ns2 gene. The AKAP7 PDE domain or N-terminally truncated AKAP7 (both lacking a nuclear localization motif), but not full-length AKAP7 or a mutant, AKAP7(H185R), PDE domain restored the infectivity of ns2 mutant MHV in bone marrow macrophages and in livers of infected mice. Interestingly, the AKAP7 PDE domain and N-terminally deleted AKAP7 were present in the cytoplasm (the site of MHV replication), whereas full-length AKAP7 was observed only in nuclei. We suggest the possibility that viral acquisition of the host AKAP7 PDE domain might have occurred during evolution, allowing diverse RNA viruses to antagonize the RNase L pathway.",2014 Jul 1,"['Gusho, Elona', 'Zhang, Rong', 'Jha, Babal K.', 'Thornbrough, Joshua M.', 'Dong, Beihua', 'Gaughan, Christina', 'Elliott, Ruth', 'Weiss, Susan R.', 'Silverman, Robert H.']",mBio,,,True
536bc0823141e21f1c5c09e92569db04cf2e8799,PMC,"Murine AKAP7 Has a 2′,5′-Phosphodiesterase Domain That Can Complement an Inactive Murine Coronavirus ns2 Gene",http://dx.doi.org/10.1128/mBio.01312-14,PMC4161237,24987090,CC BY-NC-SA,"Viral 2′,5′-phosphodiesterases (2′,5′-PDEs) help disparate RNA viruses evade the antiviral activity of interferon (IFN) by degrading 2′,5′-oligoadenylate (2-5A) activators of RNase L. A kinase anchoring proteins (AKAPs) bind the regulatory subunits of protein kinase A (PKA) to localize and organize cyclic AMP (cAMP) signaling during diverse physiological processes. Among more than 43 AKAP isoforms, AKAP7 appears to be unique in its homology to viral 2′,5′-PDEs. Here we show that mouse AKAP7 rapidly degrades 2-5A with kinetics similar to that of murine coronavirus (mouse hepatitis virus [MHV]) strain A59 ns2 and human rotavirus strain WA VP3 proteins. To determine whether AKAP7 could substitute for a viral 2′,5′-PDE, we inserted AKAP7 cDNA into an MHV genome with an inactivated ns2 gene. The AKAP7 PDE domain or N-terminally truncated AKAP7 (both lacking a nuclear localization motif), but not full-length AKAP7 or a mutant, AKAP7(H185R), PDE domain restored the infectivity of ns2 mutant MHV in bone marrow macrophages and in livers of infected mice. Interestingly, the AKAP7 PDE domain and N-terminally deleted AKAP7 were present in the cytoplasm (the site of MHV replication), whereas full-length AKAP7 was observed only in nuclei. We suggest the possibility that viral acquisition of the host AKAP7 PDE domain might have occurred during evolution, allowing diverse RNA viruses to antagonize the RNase L pathway.",2014 Jul 1,"['Gusho, Elona', 'Zhang, Rong', 'Jha, Babal K.', 'Thornbrough, Joshua M.', 'Dong, Beihua', 'Gaughan, Christina', 'Elliott, Ruth', 'Weiss, Susan R.', 'Silverman, Robert H.']",mBio,,,False
9ceee77cb6dcbc0a9568b770103698bb7603c97d,PMC,Reply to “Concerns About Misinterpretation of Recent Scientific Data Implicating Dromedary Camels in Epidemiology of Middle East Respiratory Syndrome (MERS)”,http://dx.doi.org/10.1128/mBio.01482-14,PMC4161254,25006235,CC BY-NC-SA,,2014 Jul 8,"['Alagaili, Abdulaziz N.', 'Briese, Thomas', 'Karesh, William B.', 'Daszak, Peter', 'Lipkin, W. Ian']",mBio,,,True
33bf14aff364a7ce589e97d8021006f940b1f899,PMC,Concerns about Misinterpretation of Recent Scientific Data Implicating Dromedary Camels in Epidemiology of Middle East Respiratory Syndrome (MERS),http://dx.doi.org/10.1128/mBio.01430-14,PMC4161258,25006231,CC BY-NC-SA,,2014 Jul 8,"['Samara, Emad M.', 'Abdoun, Khalid A.']",mBio,,,True
3897a0019d6f54b8c354f32eca68de8f512af39c,PMC,Seroprevalence of Respiratory Syncytial Virus IgG among Healthy Young Adults in Basic Training for the Republic of Korea Air Force,http://dx.doi.org/10.3346/jkms.2014.29.9.1325,PMC4168190,25246755,CC BY-NC,"This investigation enrolled 570 healthy young males gathered from all over the country for military service at the Republic of Korea Air Force boot camp. It confirmed RSV IgG seroprevalence by utilizing the enzyme immunoassay method just prior to undergoing basic training. The mean age of this study was 20.25±1.34 yr old. The results of their immunoassay seroprofiles showed that 561 men (98.4%) were positive, 2 (0.4%) were negative and 7 (1.2%) were equivocal belonging to the grey zone. It was confirmed that RSV is a common respiratory virus and RSV infection was encountered by almost all people before reaching adulthood in Korea. Nine basic trainees belonging to the RSV IgG negative and equivocal grey zone categories were prospectively observed for any particular vulnerability to respiratory infection during the training period of two months. However, these nine men completed their basic training without developing any specific respiratory illness. GRAPHICAL ABSTRACT: [Image: see text]",2014 Sep 2,"Park, Won-Ju",J Korean Med Sci,,,True
db6ef4648f49c12082d38056e00a106f8c2c510b,PMC,Removal of a C-terminal serine residue proximal to the inter-chain disulfide bond of a human IgG1 lambda light chain mediates enhanced antibody stability and antibody dependent cell-mediated cytotoxicity,http://dx.doi.org/10.4161/mabs.24291,PMC4169035,23567210,CC BY-NC,"Optimization of biophysical properties is a critical success factor for the developability of monoclonal antibodies with potential therapeutic applications. The inter-domain disulfide bond between light chain (Lc) and heavy chain (Hc) in human IgG1 lends structural support for antibody scaffold stability, optimal antigen binding, and normal Fc function. Recently, human IgG1λ has been suggested to exhibit significantly greater susceptibility to reduction of the inter Lc-Hc disulfide bond relative to the same disulfide bond in human IgG1κ. To understand the molecular basis for this observed difference in stability, the sequence and structure of human IgG1λ and human IgG1κ were compared. Based on this Lc comparison, three single mutations were made in the λ Lc proximal to the cysteine residue, which forms a disulfide bond with the Hc. We determined that deletion of S214 (dS) improved resistance of the association between Lc and Hc to thermal stress. In addition, deletion of this terminal serine from the Lc of IgG1λ provided further benefit, including an increase in stability at elevated pH, increased yield from transient transfection, and improved in vitro antibody dependent cell-mediated cytotoxicity (ADCC). These observations support the conclusion that the presence of the terminal serine of the λ Lc creates a weaker inter-chain disulfide bond between the Lc and Hc, leading to slightly reduced stability and a potential compromise in IgG1λ function. Our data from a human IgG1λ provide a basis for further investigation of the effects of deleting terminal serine from λLc on the stability and function of other human IgG1λ antibodies.",2013 May 1,"['Shen, Yang', 'Zeng, Lin', 'Zhu, Aiping', 'Blanc, Tim', 'Patel, Dipa', 'Pennello, Anthony', 'Bari, Amtul', 'Ng, Stanley', 'Persaud, Kris', 'Kang, Yun (Kenneth)', 'Balderes, Paul', 'Surguladze, David', 'Hindi, Sagit', 'Zhou, Qinwei', 'Ludwig, Dale L.', 'Snavely, Marshall']",MAbs,,,True
cd9a3d363cbe8225822b3b6e2ff711f4c5bd9729,PMC,Removal of a C-terminal serine residue proximal to the inter-chain disulfide bond of a human IgG1 lambda light chain mediates enhanced antibody stability and antibody dependent cell-mediated cytotoxicity,http://dx.doi.org/10.4161/mabs.24291,PMC4169035,23567210,CC BY-NC,"Optimization of biophysical properties is a critical success factor for the developability of monoclonal antibodies with potential therapeutic applications. The inter-domain disulfide bond between light chain (Lc) and heavy chain (Hc) in human IgG1 lends structural support for antibody scaffold stability, optimal antigen binding, and normal Fc function. Recently, human IgG1λ has been suggested to exhibit significantly greater susceptibility to reduction of the inter Lc-Hc disulfide bond relative to the same disulfide bond in human IgG1κ. To understand the molecular basis for this observed difference in stability, the sequence and structure of human IgG1λ and human IgG1κ were compared. Based on this Lc comparison, three single mutations were made in the λ Lc proximal to the cysteine residue, which forms a disulfide bond with the Hc. We determined that deletion of S214 (dS) improved resistance of the association between Lc and Hc to thermal stress. In addition, deletion of this terminal serine from the Lc of IgG1λ provided further benefit, including an increase in stability at elevated pH, increased yield from transient transfection, and improved in vitro antibody dependent cell-mediated cytotoxicity (ADCC). These observations support the conclusion that the presence of the terminal serine of the λ Lc creates a weaker inter-chain disulfide bond between the Lc and Hc, leading to slightly reduced stability and a potential compromise in IgG1λ function. Our data from a human IgG1λ provide a basis for further investigation of the effects of deleting terminal serine from λLc on the stability and function of other human IgG1λ antibodies.",2013 May 1,"['Shen, Yang', 'Zeng, Lin', 'Zhu, Aiping', 'Blanc, Tim', 'Patel, Dipa', 'Pennello, Anthony', 'Bari, Amtul', 'Ng, Stanley', 'Persaud, Kris', 'Kang, Yun (Kenneth)', 'Balderes, Paul', 'Surguladze, David', 'Hindi, Sagit', 'Zhou, Qinwei', 'Ludwig, Dale L.', 'Snavely, Marshall']",MAbs,,,False
76d2990a2663635e195b8a9818f9664872b6d3af,PMC,Metagenomic Assay for Identification of Microbial Pathogens in Tumor Tissues,http://dx.doi.org/10.1128/mBio.01714-14,PMC4172075,25227467,CC BY-NC-SA,"Screening for thousands of viruses and other pathogenic microorganisms, including bacteria, fungi, and parasites, in human tumor tissues will provide a better understanding of the contributory role of the microbiome in the predisposition for, causes of, and therapeutic responses to the associated cancer. Metagenomic assays designed to perform these tasks will have to include rapid and economical processing of large numbers of samples, supported by straightforward data analysis pipeline and flexible sample preparation options for multiple input tissue types from individual patients, mammals, or environmental samples. To meet these requirements, the PathoChip platform was developed by targeting viral, prokaryotic, and eukaryotic genomes with multiple DNA probes in a microarray format that can be combined with a variety of upstream sample preparation protocols and downstream data analysis. PathoChip screening of DNA plus RNA from formalin-fixed, paraffin-embedded tumor tissues demonstrated the utility of this platform, and the detection of oncogenic viruses was validated using independent PCR and deep sequencing methods. These studies demonstrate the use of the PathoChip technology combined with PCR and deep sequencing as a valuable strategy for detecting the presence of pathogens in human cancers and other diseases.",2014 Sep 16,"['Baldwin, Don A.', 'Feldman, Michael', 'Alwine, James C.', 'Robertson, Erle S.']",mBio,,,True
afa3ae140a0daa1214d7e0f550ebf2e7843f9796,PMC,Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius,http://dx.doi.org/10.1128/mBio.01484-14,PMC4173777,25205093,CC BY-NC-SA,"A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease.",2014 Sep 9,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Wozniak, Edward J.', 'Wellehan, James F. X.', 'Kincaid, Anne', 'Gordon, Marcus', 'Porter, Brian F.', 'Baumgartner, Wes', 'Stahl, Scott', 'Kelley, Karen', 'Towner, Jonathan S.', 'DeRisi, Joseph L.']",mBio,,,True
53376afd3085afd278d71264b60f7675ee51c1ee,PMC,Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius,http://dx.doi.org/10.1128/mBio.01484-14,PMC4173777,25205093,CC BY-NC-SA,"A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease.",2014 Sep 9,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Wozniak, Edward J.', 'Wellehan, James F. X.', 'Kincaid, Anne', 'Gordon, Marcus', 'Porter, Brian F.', 'Baumgartner, Wes', 'Stahl, Scott', 'Kelley, Karen', 'Towner, Jonathan S.', 'DeRisi, Joseph L.']",mBio,,,False
ffb3897218776e4404db6220334c9478605e1eec,PMC,Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius,http://dx.doi.org/10.1128/mBio.01484-14,PMC4173777,25205093,CC BY-NC-SA,"A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease.",2014 Sep 9,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Wozniak, Edward J.', 'Wellehan, James F. X.', 'Kincaid, Anne', 'Gordon, Marcus', 'Porter, Brian F.', 'Baumgartner, Wes', 'Stahl, Scott', 'Kelley, Karen', 'Towner, Jonathan S.', 'DeRisi, Joseph L.']",mBio,,,False
a8fbe3041480a8d9b3d956086066f62f4d6b5218,PMC,Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius,http://dx.doi.org/10.1128/mBio.01484-14,PMC4173777,25205093,CC BY-NC-SA,"A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease.",2014 Sep 9,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Wozniak, Edward J.', 'Wellehan, James F. X.', 'Kincaid, Anne', 'Gordon, Marcus', 'Porter, Brian F.', 'Baumgartner, Wes', 'Stahl, Scott', 'Kelley, Karen', 'Towner, Jonathan S.', 'DeRisi, Joseph L.']",mBio,,,False
5cd7388b1b475b432a662781e20513e4a41fb9d5,PMC,Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius,http://dx.doi.org/10.1128/mBio.01484-14,PMC4173777,25205093,CC BY-NC-SA,"A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease.",2014 Sep 9,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Wozniak, Edward J.', 'Wellehan, James F. X.', 'Kincaid, Anne', 'Gordon, Marcus', 'Porter, Brian F.', 'Baumgartner, Wes', 'Stahl, Scott', 'Kelley, Karen', 'Towner, Jonathan S.', 'DeRisi, Joseph L.']",mBio,,,False
021291da7cf3769e4182317703a95b6c5f7c76f9,PMC,Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius,http://dx.doi.org/10.1128/mBio.01484-14,PMC4173777,25205093,CC BY-NC-SA,"A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease.",2014 Sep 9,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Wozniak, Edward J.', 'Wellehan, James F. X.', 'Kincaid, Anne', 'Gordon, Marcus', 'Porter, Brian F.', 'Baumgartner, Wes', 'Stahl, Scott', 'Kelley, Karen', 'Towner, Jonathan S.', 'DeRisi, Joseph L.']",mBio,,,True
1a8fca50e01d853310149bc3dddcd14cfbeb32e8,PMC,Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius,http://dx.doi.org/10.1128/mBio.01484-14,PMC4173777,25205093,CC BY-NC-SA,"A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease.",2014 Sep 9,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Wozniak, Edward J.', 'Wellehan, James F. X.', 'Kincaid, Anne', 'Gordon, Marcus', 'Porter, Brian F.', 'Baumgartner, Wes', 'Stahl, Scott', 'Kelley, Karen', 'Towner, Jonathan S.', 'DeRisi, Joseph L.']",mBio,,,False
d032771cfe8cecffefae453d5ac992b09db111d3,PMC,Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius,http://dx.doi.org/10.1128/mBio.01484-14,PMC4173777,25205093,CC BY-NC-SA,"A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease.",2014 Sep 9,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Wozniak, Edward J.', 'Wellehan, James F. X.', 'Kincaid, Anne', 'Gordon, Marcus', 'Porter, Brian F.', 'Baumgartner, Wes', 'Stahl, Scott', 'Kelley, Karen', 'Towner, Jonathan S.', 'DeRisi, Joseph L.']",mBio,,,False
4ba3e67b9c30e25eaa61701184afa5c58ed096b5,PMC,Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius,http://dx.doi.org/10.1128/mBio.01484-14,PMC4173777,25205093,CC BY-NC-SA,"A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease.",2014 Sep 9,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Wozniak, Edward J.', 'Wellehan, James F. X.', 'Kincaid, Anne', 'Gordon, Marcus', 'Porter, Brian F.', 'Baumgartner, Wes', 'Stahl, Scott', 'Kelley, Karen', 'Towner, Jonathan S.', 'DeRisi, Joseph L.']",mBio,,,False
a1d0de65eff593358d81e4e990e114bc460eb725,PMC,Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius,http://dx.doi.org/10.1128/mBio.01484-14,PMC4173777,25205093,CC BY-NC-SA,"A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease.",2014 Sep 9,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Wozniak, Edward J.', 'Wellehan, James F. X.', 'Kincaid, Anne', 'Gordon, Marcus', 'Porter, Brian F.', 'Baumgartner, Wes', 'Stahl, Scott', 'Kelley, Karen', 'Towner, Jonathan S.', 'DeRisi, Joseph L.']",mBio,,,False
a25eeb43c5f7e8143b16c6237093f2156b3cef60,PMC,Undressing of Waddlia chondrophila to enrich its outer membrane proteins to develop a new species-specific ELISA,http://dx.doi.org/10.1002/2052-2975.26,PMC4184618,25356333,CC BY-NC-ND,"Waddlia chondrophila, an obligate intracellular bacterium of the Chlamydiales order, is considered as an agent of bovine abortion and a likely cause of miscarriage in humans. Its role in respiratory diseases was questioned after the detection of its DNA in clinical samples taken from patients suffering from pneumonia or bronchiolitis. To better define the role of Waddlia in both miscarriage and pneumonia, a tool allowing large-scale serological investigations of Waddlia seropositivity is needed. Therefore, enriched outer membrane proteins of W. chondrophila were used as antigens to develop a specific ELISA. After thorough analytical optimization, the ELISA was validated by comparison with micro-immunofluorescence and it showed a sensitivity above 85% with 100% specificity. The ELISA was subsequently applied to human sera to specify the role of W. chondrophila in pneumonia. Overall, 3.6% of children showed antibody reactivity against W. chondrophila but no significant difference was observed between children with and without pneumonia. Proteomic analyses were then performed using mass spectrometry, highlighting members of the outer membrane protein family as the dominant proteins. The major Waddlia putative immunogenic proteins were identified by immunoblot using positive and negative human sera. The new ELISA represents an efficient tool with high throughput applications. Although no association with pneumonia and Waddlia seropositivity was observed, this ELISA could be used to specify the role of W. chondrophila in miscarriage and in other diseases.",2014 Jan 16,"['Lienard, J', 'Croxatto, A', 'Gervaix, A', 'Posfay-Barbe, K', 'Baud, D', 'Kebbi-Beghdadi, C', 'Greub, G']",New Microbes New Infect,,,True
ae8ccebf81f9909e96af7c707cca66e5ed716b1f,PMC,"Lack of detection of Middle East respiratory syndrome coronavirus in mild and severe respiratory infections in Catalonia, northeastern Spain",http://dx.doi.org/10.1002/2052-2975.34,PMC4184620,25356335,CC BY-NC-ND,"Surveillance of Middle East respiratory syndrome coronavirus (MERS-CoV) was conducted to explore the possible introduction and circulation of this novel virus in Catalonia, northeastern Spain. Five hundred and sixty-three samples from mild and severe respiratory infections collected between January 2012 and April 2013 were screened using real-time RT-PCR. All samples were negative, suggesting that MERS-CoV is not circulating silently in Catalonia.",2014 Jan 28,"['Martínez, M J', 'Marcos, M A', 'Gonzalo, V', 'Zboromyrska, Y', 'Isanta, R', 'Torner, N', 'Martinez, A', 'Jané, M', 'Mateu, A', 'Vila, J']",New Microbes New Infect,,,True
3f5d545fbca8b7c83ff7b10f827d772cb0011aa4,PMC,Relationship between the GOLD combined COPD assessment staging system and bacterial isolation,http://dx.doi.org/10.2147/COPD.S70620,PMC4186572,25298733,CC BY-NC,"BACKGROUND: Acute exacerbations, which are a significant cause of mortality and morbidity, adversely affect chronic obstructive pulmonary disease (COPD) prognosis by accelerating loss of lung function. It is important to know the microorganisms that commonly cause exacerbations in the patient groups classified according to clinical and functional characteristics for fast and accurate treatment of acute exacerbations. OBJECTIVES: The last Global Initiative for Chronic Obstructive Lung Disease (GOLD) publication recommended a new staging system containing obstruction degree, frequency of exacerbations, and quality of life questionnaires. This study is designed to analyze the relationship between the bacteria isolated in acute exacerbations and new GOLD stages. METHODS: Potentially pathogenic bacteria (PPB) isolation with culture and polymerase chain reaction methods were obtained from 114 acute exacerbation COPD patients, classified into A, B, C, and D groups by analyzing the forced expiratory volume in 1 second (FEV(1)) value, COPD Assessment Test (CAT) score, and exacerbation frequency according to the new GOLD staging system. RESULTS: There was a significant correlation between exacerbation frequency and PPB isolation (P=0.002). There was no relationship between GOLD stage, FEV(1), and CAT score with PPB isolation. The isolated bacteria diversity and mixed infection frequency were higher in the GOLD stage D group. Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii were isolated only from D group patients. CONCLUSION: Bacterial infection may cause an acute exacerbation equally in each stage for COPD. The difference in bacterial etiology is more related to exacerbation frequency than FEV(1) and CAT scores for an acute exacerbation. Determining exacerbation frequency is significant for treatment success in empirical antibiotic selection.",2014 Sep 27,"['Aydemir, Yusuf', 'Aydemir, Özlem', 'Kalem, Fatma']",Int J Chron Obstruct Pulmon Dis,,,True
a7dea443868b1327fef754465f3792ea33a224ca,PMC,Effector biology during biotrophic invasion of plant cells,http://dx.doi.org/10.4161/viru.29652,PMC4189876,25513771,CC BY-NC,"Several obligate biotrophic phytopathogens, namely oomycetes and fungi, invade and feed on living plant cells through specialized structures known as haustoria. Deploying an arsenal of secreted proteins called effectors, these pathogens balance their parasitic propagation by subverting plant immunity without sacrificing host cells. Such secreted proteins, which are thought to be delivered by haustoria, conceivably reprogram host cells and instigate structural modifications, in addition to the modulation of various cellular processes. As effectors represent tools to assist disease resistance breeding, this short review provides a bird’s eye view on the relationship between the virulence function of effectors and their subcellular localization in host cells.",2014 Oct 1,"['Chaudhari, Prateek', 'Ahmed, Bulbul', 'Joly, David L', 'Germain, Hugo']",Virulence,,,True
da70e84ba93bb87634a681d7f61a44be543e8549,PMC,Rhinovirus Associated Severe Respiratory Failure in Immunocompetent Adult Patient,http://dx.doi.org/10.4046/trd.2014.77.3.132,PMC4192311,25309608,CC BY-NC,"Rhinovirus infection is typically associated with the common cold and has rarely been reported as a cause of severe pneumonia in immunocompetent adults. A 55-year-old previous healthy woman, who consumed half a bottle of alcohol daily, presented with respiratory failure after one week of upper respiratory infection symptoms. Radiography revealed bilateral, diffuse ground glass opacity with patchy consolidation in the whole lung field; bronchoalveolar lavage fluid analysis indicated that rhinovirus was the causative organism. After five days of conservative support, the symptoms and radiographic findings began to improve. We report this rare case of rhinovirus pneumonia in an otherwise healthy host along with a review of references.",2014 Sep 30,"['Kim, Kiwook', 'Song, Yeon Han', 'Park, Joo-Hyun', 'Park, Hye Kyeong', 'Kim, Su Young', 'Jung, Hun', 'Lee, Sung-Soon', 'Koo, Hyeon-Kyoung']",Tuberc Respir Dis (Seoul),,,True
2ffacfd58f57a95344119c15d27560cdeaea2285,PMC,The calcium-dependent ribonuclease XendoU promotes ER network formation through local RNA degradation,http://dx.doi.org/10.1083/jcb.201406037,PMC4195833,25287301,CC BY-NC-SA,"How cells shape and remodel organelles in response to cellular signals is a poorly understood process. Using Xenopus laevis egg extract, we found that increases in cytosolic calcium lead to the activation of an endogenous ribonuclease, XendoU. A fraction of XendoU localizes to the endoplasmic reticulum (ER) and is required for nuclear envelope assembly and ER network formation in a catalysis-dependent manner. Using a purified vesicle fusion assay, we show that XendoU functions on the surface of ER membranes to promote RNA cleavage and ribonucleoprotein (RNP) removal. Additionally, RNA removal from the surface of vesicles by RNase treatment leads to increased ER network formation. Using human tissue culture cells, we found that hEndoU localizes to the ER, where it promotes the formation of ER tubules in a catalysis-dependent manner. Together, these results demonstrate that calcium-activated removal of RNA from membranes by XendoU promotes and refines ER remodeling and the formation of tubular ER.",2014 Oct 13,"['Schwarz, Dianne S.', 'Blower, Michael D.']",J Cell Biol,,,True
6b5cf0f42fe4c4ddd41007e4e1a59b625c1ebe88,PMC,The calcium-dependent ribonuclease XendoU promotes ER network formation through local RNA degradation,http://dx.doi.org/10.1083/jcb.201406037,PMC4195833,25287301,CC BY-NC-SA,"How cells shape and remodel organelles in response to cellular signals is a poorly understood process. Using Xenopus laevis egg extract, we found that increases in cytosolic calcium lead to the activation of an endogenous ribonuclease, XendoU. A fraction of XendoU localizes to the endoplasmic reticulum (ER) and is required for nuclear envelope assembly and ER network formation in a catalysis-dependent manner. Using a purified vesicle fusion assay, we show that XendoU functions on the surface of ER membranes to promote RNA cleavage and ribonucleoprotein (RNP) removal. Additionally, RNA removal from the surface of vesicles by RNase treatment leads to increased ER network formation. Using human tissue culture cells, we found that hEndoU localizes to the ER, where it promotes the formation of ER tubules in a catalysis-dependent manner. Together, these results demonstrate that calcium-activated removal of RNA from membranes by XendoU promotes and refines ER remodeling and the formation of tubular ER.",2014 Oct 13,"['Schwarz, Dianne S.', 'Blower, Michael D.']",J Cell Biol,,,False
e8d81153777e9f92cbc2bc9ea03ed1f0d0b78543,PMC,"Group B Betacoronavirus in Rhinolophid Bats, Japan",http://dx.doi.org/10.1292/jvms.14-0012,PMC4197156,24871548,CC BY-NC-ND,"We report group B Betacoronavirus infection in little Japanese horseshoe bats in Iwate prefecture. We then used reverse-transcription PCR to look for the coronavirus RNA-dependent RNA polymerase gene in fecal samples collected from 27 little Japanese horseshoe bats and found eight were provisionally positive. We had a success in the nucleotide sequencing of six of the eight positive samples and compared them with those of authentic coronaviruses. We found that these six samples were positive in coronavirus infection, and they belonged to the group B Betacornavirus by phylogenetic analysis. Virus isolation using the Vero cell culture was unsuccessful. Pathogenic trait of these bat coronaviruses remained unexplored.",2014 Sep 27,"['SUZUKI, Jin', 'SATO, Ryota', 'KOBAYASHI, Tomoya', 'AOI, Toshiki', 'HARASAWA, Ryô']",J Vet Med Sci,,,True
d040e6d03a6e02e8f21012e1fbd04b6d21da5284,PMC,"US-Like Strain of Porcine Epidemic Diarrhea Virus Outbreaks in Taiwan, 2013–2014",http://dx.doi.org/10.1292/jvms.14-0098,PMC4197162,24898162,CC BY-NC-ND,"Since late 2013, several outbreaks of porcine epidemic diarrhea virus (PEDV) infection have emerged in Taiwan. Suckling piglets under 2 weeks of age showed severe vomiting and watery yellowish diarrhea with morbidity and mortality ranging from 80 to 100% and 90 to 100%, respectively. A total of 68 samples from 25 pig farms were confirmed as positive for PEDV and negative for rotavirus and transmissible gastroenteritis virus by reverse transcription PCR, and the partial S gene of PEDV was analyzed. Phylogenetic analysis places all 18 Taiwanese PEDV isolates collected during this outbreak in the same clade as the US strains of PEDV. This novel PEDV is prevailing and currently causing severe outbreaks in Taiwan.",2014 Sep 5,"['LIN, Chao-Nan', 'CHUNG, Wen-Bin', 'CHANG, Shu-Wei', 'WEN, Chi-Chi', 'LIU, Hung', 'CHIEN, Chi-Hsien', 'CHIOU, Ming-Tang']",J Vet Med Sci,,,True
d5bd631a3627f3ef1fef60860af608871fa52271,PMC,Consultation-liaison psychiatry in China,http://dx.doi.org/10.3969/j.issn.1002-0829.2012.03.001,PMC4198843,25324616,CC BY-NC-SA,"Consultation-liaison psychiatry (CLP) was first established in China after liberation in 1949. It has developed more rapidly over the last two decades but, despite major regional differences in the level of CLP, the overall practice of CLP in the country remains quite basic, largely limited to case-based consultation with other medical departments. There is little ongoing collaboration between departments of psychiatry and other departments, and medical students and non-psychiatric clinicians rarely get training in CLP.",2012 Jun,"['Ji, Jianlin', 'Ye, Chenyu']",Shanghai Arch Psychiatry,,,True
4e2387a88720584e25e0f6418be2491523e288af,PMC,Coronavirus NSP6 restricts autophagosome expansion,http://dx.doi.org/10.4161/auto.29309,PMC4203519,24991833,CC BY-NC,"Autophagy is a cellular response to starvation that generates autophagosomes to carry long-lived proteins and cellular organelles to lysosomes for degradation. Activation of autophagy by viruses can provide an innate defense against infection, and for (+) strand RNA viruses autophagosomes can facilitate assembly of replicase proteins. We demonstrated that nonstructural protein (NSP) 6 of the avian coronavirus, infectious bronchitis virus (IBV), generates autophagosomes from the ER. A statistical analysis of MAP1LC3B puncta showed that NSP6 induced greater numbers of autophagosomes per cell compared with starvation, but the autophagosomes induced by NSP6 had smaller diameters compared with starvation controls. Small diameter autophagosomes were also induced by infection of cells with IBV, and by NSP6 proteins of MHV and SARS and NSP5, NSP6, and NSP7 of arterivirus PRRSV. Analysis of WIPI2 puncta induced by NSP6 suggests that NSP6 limits autophagosome diameter at the point of omegasome formation. IBV NSP6 also limited autophagosome and omegasome expansion in response to starvation and Torin1 and could therefore limit the size of autophagosomes induced following inhibition of MTOR signaling, as well as those induced independently by the NSP6 protein itself. MAP1LC3B-puncta induced by NSP6 contained SQSTM1, which suggests they can incorporate autophagy cargos. However, NSP6 inhibited the autophagosome/lysosome expansion normally seen following starvation. Taken together the results show that coronavirus NSP6 proteins limit autophagosome expansion, whether they are induced directly by the NSP6 protein, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.",2014 Aug 1,"['Cottam, Eleanor M', 'Whelband, Matthew C', 'Wileman, Thomas']",Autophagy,,,True
a6de1d34caf397b50cab6127fd38a29adfa9db33,PMC,Coronavirus NSP6 restricts autophagosome expansion,http://dx.doi.org/10.4161/auto.29309,PMC4203519,24991833,CC BY-NC,"Autophagy is a cellular response to starvation that generates autophagosomes to carry long-lived proteins and cellular organelles to lysosomes for degradation. Activation of autophagy by viruses can provide an innate defense against infection, and for (+) strand RNA viruses autophagosomes can facilitate assembly of replicase proteins. We demonstrated that nonstructural protein (NSP) 6 of the avian coronavirus, infectious bronchitis virus (IBV), generates autophagosomes from the ER. A statistical analysis of MAP1LC3B puncta showed that NSP6 induced greater numbers of autophagosomes per cell compared with starvation, but the autophagosomes induced by NSP6 had smaller diameters compared with starvation controls. Small diameter autophagosomes were also induced by infection of cells with IBV, and by NSP6 proteins of MHV and SARS and NSP5, NSP6, and NSP7 of arterivirus PRRSV. Analysis of WIPI2 puncta induced by NSP6 suggests that NSP6 limits autophagosome diameter at the point of omegasome formation. IBV NSP6 also limited autophagosome and omegasome expansion in response to starvation and Torin1 and could therefore limit the size of autophagosomes induced following inhibition of MTOR signaling, as well as those induced independently by the NSP6 protein itself. MAP1LC3B-puncta induced by NSP6 contained SQSTM1, which suggests they can incorporate autophagy cargos. However, NSP6 inhibited the autophagosome/lysosome expansion normally seen following starvation. Taken together the results show that coronavirus NSP6 proteins limit autophagosome expansion, whether they are induced directly by the NSP6 protein, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.",2014 Aug 1,"['Cottam, Eleanor M', 'Whelband, Matthew C', 'Wileman, Thomas']",Autophagy,,,False
ff3786e07cdc8f41bc8347c875b84813cbb8d3eb,PMC,Ultra-Low-Dose Chest CT in Patients with Neutropenic Fever and Hematologic Malignancy: Image Quality and Its Diagnostic Performance,http://dx.doi.org/10.4143/crt.2013.132,PMC4206072,25308150,CC BY-NC,"PURPOSE: The aim of this study was to evaluate the image quality of ultra-low-dose computed tomography (ULDCT) and its diagnostic performance in making a specific diagnosis of pneumonia in febrile neutropenic patients with hematological malignancy. MATERIALS AND METHODS: ULDCT was performed prospectively in 207 febrile neutropenic patients with hematological malignancy. Three observers independently recorded the presence of lung parenchymal abnormality, and also indicated the cause of the lung parenchymal abnormality between infectious and noninfectious causes. If infectious pneumonia was considered the cause of lung abnormalities, they noted the two most appropriate diagnoses among four infectious conditions, including fungal, bacterial, viral, and Pneumocystis pneumonia. Sensitivity for correct diagnoses and receiver operating characteristic (ROC) curve analysis for evaluation of diagnostic accuracy were calculated. Interobserver agreements were determined using intraclass correlation coefficient. RESULTS: Of 207 patients, 139 (67%) had pneumonia, 12 had noninfectious lung disease, and 56 had no remarkable chest computed tomography (CT) (20 with extrathoracic fever focus and 36 with no specific disease). Mean radiation expose dose of ULDCT was 0.60±0.15 mSv. Each observer regarded low-dose CT scans as unacceptable in only four (1.9%), one (0.5%), and three (1.5%) cases of ULDCTs. Sensitivity and area under the ROC curve in making a specific pneumonia diagnosis were 63.0%, 0.65 for reader 1; 63.0%, 0.61 for reader 2; and 65.0%, 0.62 for reader 3; respectively CONCLUSION: ULDCT, with a sub-mSv radiation dose and acceptable image quality, provides ready and reasonably acceptable diagnostic information for pulmonary infection in febrile neutropenic patients with hematologic malignancy",2014 Oct 18,"['Kim, Hae Jin', 'Park, So Young', 'Lee, Ho Yun', 'Lee, Kyung Soo', 'Shin, Kyung Eun', 'Moon, Jung Won']",Cancer Res Treat,,,True
497065a88412aca3ce4d3de9ebad13ce175e5f18,PMC,Parental bonding and attitudes toward suicide among medical college students in Japan,http://dx.doi.org/10.2147/NDT.S70818,PMC4211911,25364256,CC BY-NC,"BACKGROUND: Suicide is a grave public health issue that is responsible for a high mortality rate among individuals aged 15–44 years. Attitudes toward suicide among medical staff members have been associated with appropriate therapeutic responses to suicidal individuals. The aim of this study was to examine the effects of parental rearing on attitudes toward suicide among Japanese medical college students. METHODS: We examined the association between parental bonding and attitudes toward suicide in 160 medical college students in Japan. The Parental Bonding Instrument was used to assess the attitudes and behaviors of parents. The attitudes toward suicide were evaluated using the Japanese version of the Attitudes Toward Suicide questionnaire. RESULTS: The mean age of the subjects was 25.2±4.0 years old. The majority of the participants in our study agreed that anyone could commit suicide (88.8%) and that suicide is preventable (86.3%). After adjusting for age and sex, multivariate regression analysis revealed that maternal care approached a statistically significant association with the “right to suicide” attitude. Under the same conditions, maternal care was shown to be significantly associated with the “common occurrence” attitude. No other significant relationships were observed between parental bonding and attitudes toward suicide. CONCLUSION: This study suggests that a higher level of maternal care ensures that children think that suicide occurs less commonly. The promotion of best practices for suicide prevention among medical students is needed. Child rearing support might be associated with suicide prevention.",2014 Oct 23,"['Hashimoto, Kojiro', 'Sugawara, Norio', 'Tanaka, Osamu', 'Nakamura, Kazuhiko', 'Yasui-Furukori, Norio']",Neuropsychiatr Dis Treat,,,True
7d2c839823df05875ad1170a68a88c981bf0e859,PMC,"CSBF/C10orf99, a novel potential cytokine, inhibits colon cancer cell growth through inducing G1 arrest",http://dx.doi.org/10.1038/srep06812,PMC4212244,25351403,CC BY-NC-SA,"Cytokines are soluble proteins that exert their functions by binding specific receptors. Many cytokines play essential roles in carcinogenesis and have been developed for the treatment of cancer. In this study, we identified a novel potential cytokine using immunogenomics designated colon-derived SUSD2 binding factor (CSBF), also known as chromosome 10 open reading frame 99 (C10orf99). CSBF/C10orf99 is a classical secreted protein with predicted molecular mass of 6.5 kDa, and a functional ligand of Sushi Domain Containing 2 (SUSD2). CSBF/C10orf99 has the highest expression level in colon tissue. Both CSBF/C10orf99 and SUSD2 are down-regulated in colon cancer tissues and cell lines with different regulation mechanisms. CSBF/C10orf99 interacts with SUSD2 to inhibit colon cancer cell growth and induce G1 cell cycle arrest by down-regulating cyclin D and cyclin-dependent kinase 6 (CDK6). CSBF/C10orf99 displays a bell-shaped activity curve with the optimal effect at ~10 ng/ml. Its growth inhibitory effects can be blocked by sSUSD2-Fc soluble protein. Our results suggest that CSBF/C10orf99 is a novel potential cytokine with tumor suppressor functions.",2014 Oct 29,"['Pan, Wen', 'Cheng, Yingying', 'Zhang, Heyu', 'Liu, Baocai', 'Mo, Xiaoning', 'Li, Ting', 'Li, Lin', 'Cheng, Xiaojing', 'Zhang, Lianhai', 'Ji, Jiafu', 'Wang, Pingzhang', 'Han, Wenling']",Sci Rep,,,True
ab312eb3286e189488707ea7ac8551401a178940,PMC,Arenavirus Stable Signal Peptide Is the Keystone Subunit for Glycoprotein Complex Organization,http://dx.doi.org/10.1128/mBio.02063-14,PMC4217180,25352624,CC BY-NC-SA,"The rodent arenavirus glycoprotein complex encodes a stable signal peptide (SSP) that is an essential structural component of mature virions. The SSP, GP1, and GP2 subunits of the trimeric glycoprotein complex noncovalently interact to stud the surface of virions and initiate arenavirus infectivity. Nascent glycoprotein production undergoes two proteolytic cleavage events: first within the endoplasmic reticulum (ER) to cleave SSP from the remaining precursor GP1/2 (glycoprotein complex [GPC]) glycoprotein and second within the Golgi stacks by the cellular SKI-1/S1P for GP1/2 processing to yield GP1 and GP2 subunits. Cleaved SSP is not degraded but retained as an essential glycoprotein subunit. Here, we defined functions of the 58-amino-acid lymphocytic choriomeningitis virus (LCMV) SSP in regard to glycoprotein complex processing and maturation. Using molecular biology techniques, confocal microscopy, and flow cytometry, we detected SSP at the plasma membrane of transfected cells. Further, we identified a sorting signal (FLLL) near the carboxyl terminus of SSP that is required for glycoprotein maturation and trafficking. In the absence of SSP, the glycoprotein accumulated within the ER and was unable to undergo processing by SKI-1/S1P. Mutation of this highly conserved FLLL motif showed impaired glycoprotein processing and secretory pathway trafficking, as well as defective surface expression and pH-dependent membrane fusion. Immunoprecipitation of SSP confirmed an interaction between the signal peptide and the GP2 subunit; however, mutations within this FLLL motif disrupted the association of the GP1 subunit with the remaining glycoprotein complex.",2014 Oct 28,"['Bederka, Lydia H.', 'Bonhomme, Cyrille J.', 'Ling, Emily L.', 'Buchmeier, Michael J.']",mBio,,,True
0afa3ea846396533c7ca515968abcfea3f895082,PMC,Bone Marrow Dendritic Cells from Mice with an Altered Microbiota Provide Interleukin 17A-Dependent Protection against Entamoeba histolytica Colitis,http://dx.doi.org/10.1128/mBio.01817-14,PMC4222101,25370489,CC BY-NC-SA,"There is an emerging paradigm that the human microbiome is central to many aspects of health and may have a role in preventing enteric infection. Entamoeba histolytica is a major cause of amebic diarrhea in developing countries. It colonizes the colon lumen in close proximity to the gut microbiota. Interestingly, not all individuals are equally susceptible to E. histolytica infection. Therefore, as the microbiota is highly variable within individuals, we sought to determine if a component of the microbiota could regulate susceptibility to infection. In studies utilizing a murine model, we demonstrated that colonization of the gut with the commensal Clostridia-related bacteria known as segmented filamentous bacteria (SFB) is protective during  E. histolytica infection. SFB colonization in this model was associated with elevated cecal levels of interleukin 17A (IL-17A), dendritic cells, and neutrophils. Bone marrow-derived dendritic cells (BMDCs) from SFB-colonized mice had higher levels of IL-23 production in response to stimulation with trophozoites. Adoptive transfer of BMDCs from an SFB(+) to an SFB(−) mouse was sufficient to provide protection against E. histolytica. IL-17A induction during BMDC transfer was necessary for this protection. This work demonstrates that intestinal colonization with a specific commensal bacterium can provide protection during amebiasis in a murine model. Most importantly, this work demonstrates that the microbiome can mediate protection against an enteric infection via extraintestinal effects on bone marrow-derived dendritic cells.",2014 Nov 4,"['Burgess, Stacey L.', 'Buonomo, Erica', 'Carey, Maureen', 'Cowardin, Carrie', 'Naylor, Caitlin', 'Noor, Zannatun', 'Wills-Karp, Marsha', 'Petri, William A.']",mBio,,,True
679aafff5a2403fb48ab7bf416b6d5d97c02b798,PMC,Middle East respiratory syndrome coronavirus: epidemiology and disease control measures,http://dx.doi.org/10.2147/IDR.S51283,PMC4226520,25395865,CC BY-NC,"The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in 2012 resulted in an increased concern of the spread of the infection globally. MERS-CoV infection had previously caused multiple health-care-associated outbreaks and resulted in transmission of the virus within families. Community onset MERS-CoV cases continue to occur. Dromedary camels are currently the most likely animal to be linked to human MERS-CoV cases. Serologic tests showed significant infection in adult camels compared to juvenile camels. The control of MERS-CoV infection relies on prompt identification of cases within health care facilities, with institutions applying appropriate infection control measures. In addition, determining the exact route of transmission from camels to humans would further add to the control measures of MERS-CoV infection.",2014 Nov 3,"['Al-Tawfiq, Jaffar A', 'Memish, Ziad A']",Infect Drug Resist,,,True
9033adf08248ec28fb49e61abe6c1209d7811843,PMC,Requirement of CRTC1 coactivator for hepatitis B virus transcription,http://dx.doi.org/10.1093/nar/gku925,PMC4227773,25300488,CC BY-NC,"Transcription of hepatitis B virus (HBV) from the covalently closed circular DNA (cccDNA) template is essential for its replication. Suppressing the level and transcriptional activity of cccDNA might have anti-HBV effect. Although cellular transcription factors, such as CREB, which mediate HBV transcription, have been well described, transcriptional coactivators that facilitate this process are incompletely understood. In this study we showed that CREB-regulated transcriptional coactivator 1 (CRTC1) is required for HBV transcription and replication. The steady-state levels of CRTC1 protein were elevated in HBV-positive hepatoma cells and liver tissues. Ectopic expression of CRTC1 or its homolog CRTC2 or CRTC3 in hepatoma cells stimulated the activity of the preS2/S promoter of HBV, whereas overexpression of a dominant inactive form of CRTC1 inhibited HBV transcription. CRTC1 interacts with CREB and they are mutually required for the recruitment to the preS2/S promoter on cccDNA and for the activation of HBV transcription. Accumulation of pregenomic RNA (pgRNA) and cccDNA was observed when CRTC1 or its homologs were overexpressed, whereas the levels of pgRNA, cccDNA and secreted HBsAg were diminished when CRTC1 was compromised. In addition, HBV transactivator protein HBx stabilized CRTC1 and promoted its activity on HBV transcription. Our work reveals an essential role of CRTC1 coactivator in facilitating and supporting HBV transcription and replication.",2014 Nov 10,"['Tang, Hei-Man Vincent', 'Gao, Wei-Wei', 'Chan, Chi-Ping', 'Cheng, Yun', 'Chaudhary, Vidyanath', 'Deng, Jian-Jun', 'Yuen, Kit-San', 'Wong, Chun-Ming', 'Ng, Irene Oi-Lin', 'Kok, Kin-Hang', 'Zhou, Jie', 'Jin, Dong-Yan']",Nucleic Acids Res,,,True
ba3ee3020f475ec039824850daa9bad88845683a,PMC,Requirement of CRTC1 coactivator for hepatitis B virus transcription,http://dx.doi.org/10.1093/nar/gku925,PMC4227773,25300488,CC BY-NC,"Transcription of hepatitis B virus (HBV) from the covalently closed circular DNA (cccDNA) template is essential for its replication. Suppressing the level and transcriptional activity of cccDNA might have anti-HBV effect. Although cellular transcription factors, such as CREB, which mediate HBV transcription, have been well described, transcriptional coactivators that facilitate this process are incompletely understood. In this study we showed that CREB-regulated transcriptional coactivator 1 (CRTC1) is required for HBV transcription and replication. The steady-state levels of CRTC1 protein were elevated in HBV-positive hepatoma cells and liver tissues. Ectopic expression of CRTC1 or its homolog CRTC2 or CRTC3 in hepatoma cells stimulated the activity of the preS2/S promoter of HBV, whereas overexpression of a dominant inactive form of CRTC1 inhibited HBV transcription. CRTC1 interacts with CREB and they are mutually required for the recruitment to the preS2/S promoter on cccDNA and for the activation of HBV transcription. Accumulation of pregenomic RNA (pgRNA) and cccDNA was observed when CRTC1 or its homologs were overexpressed, whereas the levels of pgRNA, cccDNA and secreted HBsAg were diminished when CRTC1 was compromised. In addition, HBV transactivator protein HBx stabilized CRTC1 and promoted its activity on HBV transcription. Our work reveals an essential role of CRTC1 coactivator in facilitating and supporting HBV transcription and replication.",2014 Nov 10,"['Tang, Hei-Man Vincent', 'Gao, Wei-Wei', 'Chan, Chi-Ping', 'Cheng, Yun', 'Chaudhary, Vidyanath', 'Deng, Jian-Jun', 'Yuen, Kit-San', 'Wong, Chun-Ming', 'Ng, Irene Oi-Lin', 'Kok, Kin-Hang', 'Zhou, Jie', 'Jin, Dong-Yan']",Nucleic Acids Res,,,False
e47a7616bf5b35202811dcb713b4025735dd2500,PMC,RAN translation and frameshifting as translational challenges at simple repeats of human neurodegenerative disorders,http://dx.doi.org/10.1093/nar/gku794,PMC4231732,25217582,CC BY-NC,"Repeat-associated disorders caused by expansions of short sequences have been classified as coding and noncoding and are thought to be caused by protein gain-of-function and RNA gain-of-function mechanisms, respectively. The boundary between such classifications has recently been blurred by the discovery of repeat-associated non-AUG (RAN) translation reported in spinocerebellar ataxia type 8, myotonic dystrophy type 1, fragile X tremor/ataxia syndrome and C9ORF72 amyotrophic lateral sclerosis and frontotemporal dementia. This noncanonical translation requires no AUG start codon and can initiate in multiple frames of CAG, CGG and GGGGCC repeats of the sense and antisense strands of disease-relevant transcripts. RNA structures formed by the repeats have been suggested as possible triggers; however, the precise mechanism of the translation initiation remains elusive. Templates containing expansions of microsatellites have also been shown to challenge translation elongation, as frameshifting has been recognized across CAG repeats in spinocerebellar ataxia type 3 and Huntington's disease. Determining the critical requirements for RAN translation and frameshifting is essential to decipher the mechanisms that govern these processes. The contribution of unusual translation products to pathogenesis needs to be better understood. In this review, we present current knowledge regarding RAN translation and frameshifting and discuss the proposed mechanisms of translational challenges imposed by simple repeat expansions.",2014 Oct 29,"['Wojciechowska, Marzena', 'Olejniczak, Marta', 'Galka-Marciniak, Paulina', 'Jazurek, Magdalena', 'Krzyzosiak, Wlodzimierz J.']",Nucleic Acids Res,,,True
a841a20b663330228ca243c8c25753fff73cfa4e,PMC,RAN translation and frameshifting as translational challenges at simple repeats of human neurodegenerative disorders,http://dx.doi.org/10.1093/nar/gku794,PMC4231732,25217582,CC BY-NC,"Repeat-associated disorders caused by expansions of short sequences have been classified as coding and noncoding and are thought to be caused by protein gain-of-function and RNA gain-of-function mechanisms, respectively. The boundary between such classifications has recently been blurred by the discovery of repeat-associated non-AUG (RAN) translation reported in spinocerebellar ataxia type 8, myotonic dystrophy type 1, fragile X tremor/ataxia syndrome and C9ORF72 amyotrophic lateral sclerosis and frontotemporal dementia. This noncanonical translation requires no AUG start codon and can initiate in multiple frames of CAG, CGG and GGGGCC repeats of the sense and antisense strands of disease-relevant transcripts. RNA structures formed by the repeats have been suggested as possible triggers; however, the precise mechanism of the translation initiation remains elusive. Templates containing expansions of microsatellites have also been shown to challenge translation elongation, as frameshifting has been recognized across CAG repeats in spinocerebellar ataxia type 3 and Huntington's disease. Determining the critical requirements for RAN translation and frameshifting is essential to decipher the mechanisms that govern these processes. The contribution of unusual translation products to pathogenesis needs to be better understood. In this review, we present current knowledge regarding RAN translation and frameshifting and discuss the proposed mechanisms of translational challenges imposed by simple repeat expansions.",2014 Oct 29,"['Wojciechowska, Marzena', 'Olejniczak, Marta', 'Galka-Marciniak, Paulina', 'Jazurek, Magdalena', 'Krzyzosiak, Wlodzimierz J.']",Nucleic Acids Res,,,True
246f59ddffedd4a166b9317dee38bdf6077b2f3f,PMC,Identification of novel multitargeted PPARα/γ/δ pan agonists by core hopping of rosiglitazone,http://dx.doi.org/10.2147/DDDT.S70383,PMC4232041,25422585,CC BY-NC,"The thiazolidinedione class peroxisome proliferator-activated receptor gamma (PPARγ) agonists are restricted in clinical use as antidiabetic agents because of side effects such as edema, weight gain, and heart failure. The single and selective agonism of PPARγ is the main cause of these side effects. Multitargeted PPARα/γ/δ pan agonist development is the hot topic in the antidiabetic drug research field. In order to identify PPARα/γ/δ pan agonists, a compound database was established by core hopping of rosiglitazone, which was then docked into a PPARα/γ/δ active site to screen out a number of candidate compounds with a higher docking score and better interaction with the active site. Further, absorption, distribution, metabolism, excretion, and toxicity prediction was done to give eight compounds. Molecular dynamics simulation of the representative Cpd#1 showed more favorable binding conformation for PPARs receptor than the original ligand. Cpd#1 could act as a PPARα/γ/δ pan agonist for novel antidiabetic drug research.",2014 Nov 7,"['Wang, Xue-Jiao', 'Zhang, Jun', 'Wang, Shu-Qing', 'Xu, Wei-Ren', 'Cheng, Xian-Chao', 'Wang, Run-Ling']",Drug Des Devel Ther,,,True
73706c27f129eddf80395baf777ba70dd9432e8e,PMC,S-layers: principles and applications,http://dx.doi.org/10.1111/1574-6976.12063,PMC4232325,24483139,CC BY-NC-ND,"Monomolecular arrays of protein or glycoprotein subunits forming surface layers (S-layers) are one of the most commonly observed prokaryotic cell envelope components. S-layers are generally the most abundantly expressed proteins, have been observed in species of nearly every taxonomical group of walled bacteria, and represent an almost universal feature of archaeal envelopes. The isoporous lattices completely covering the cell surface provide organisms with various selection advantages including functioning as protective coats, molecular sieves and ion traps, as structures involved in surface recognition and cell adhesion, and as antifouling layers. S-layers are also identified to contribute to virulence when present as a structural component of pathogens. In Archaea, most of which possess S-layers as exclusive wall component, they are involved in determining cell shape and cell division. Studies on structure, chemistry, genetics, assembly, function, and evolutionary relationship of S-layers revealed considerable application potential in (nano)biotechnology, biomimetics, biomedicine, and synthetic biology.",2014 Sep 24,"['Sleytr, Uwe B', 'Schuster, Bernhard', 'Egelseer, Eva-Maria', 'Pum, Dietmar']",FEMS Microbiol Rev,,,True
b439deefbf5429abf9b27dc5bed6bee148c3dfa5,PMC,Detection of respiratory viruses by real-time polymerase chain reaction in outpatients with acute respiratory infection,http://dx.doi.org/10.1590/0074-0276140046,PMC4238762,25317699,CC BY-NC,"Viruses are the major contributors to the morbidity and mortality of upper and lower acute respiratory infections (ARIs) for all age groups. The aim of this study was to determine the frequencies for a large range of respiratory viruses using a sensitive molecular detection technique in specimens from outpatients of all ages with ARIs. Nasopharyngeal aspirates were obtained from 162 individuals between August 2007-August 2009. Twenty-three pathogenic respiratory agents, 18 respiratory viruses and five bacteria were investigated using multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) and indirect immunofluorescence assay (IIF). Through IIF, 33 (20.4%) specimens with respiratory virus were recognised, with influenza virus representing over half of the positive samples. Through a multiplex real-time RT-PCR assay, 88 (54.3%) positive samples were detected; the most prevalent respiratory viral pathogens were influenza, human rhinovirus and respiratory syncytial virus (RSV). Six cases of viral co-detection were observed, mainly involving RSV. The use of multiplex real-time RT-PCR increased the viral detection by 33.9% and revealed a larger number of respiratory viruses implicated in ARI cases, including the most recently described respiratory viruses [human bocavirus, human metapneumovirus, influenza A (H1N1) pdm09 virus, human coronavirus (HCoV) NL63 and HCoV HKU1].",2014 Sep,"['Martins, Ronaldo Bragança', 'Carney, Sharon', 'Goldemberg, Daniel', 'Bonine, Lucas', 'Spano, Liliana Cruz', 'Siqueira, Marilda', 'Checon, Rita Elizabeth']",Mem Inst Oswaldo Cruz,,,True
7e7c6670854897412ce9930eefc95f348ae432a2,PMC,A Scenario-Based Evaluation of the Middle East Respiratory Syndrome Coronavirus and the Hajj,http://dx.doi.org/10.1111/risa.12253,PMC4238841,25041625,CC BY-NC-ND,"Between April 2012 and June 2014, 820 laboratory-confirmed cases of the Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported in the Arabian Peninsula, Europe, North Africa, Southeast Asia, the Middle East, and the United States. The observed epidemiology is different to SARS, which showed a classic epidemic curve and was over in eight months. The much longer persistence of MERS-CoV in the population, with a lower reproductive number, some evidence of human-to-human transmission but an otherwise sporadic pattern, is difficult to explain. Using available epidemiological data, we implemented mathematical models to explore the transmission dynamics of MERS-CoV in the context of mass gatherings such as the Hajj pilgrimage, and found a discrepancy between the observed and expected epidemiology. The fact that no epidemic occurred in returning Hajj pilgrims in either 2012 or 2013 contradicts the long persistence of the virus in human populations. The explanations for this discrepancy include an ongoing, repeated nonhuman/sporadic source, a large proportion of undetected or unreported human-to-human cases, or a combination of the two. Furthermore, MERS-CoV is occurring in a region that is a major global transport hub and hosts significant mass gatherings, making it imperative to understand the source and means of the yet unexplained and puzzling ongoing persistence of the virus in the human population.",2014 Jan 1,"['Gardner, Lauren M', 'Rey, David', 'Heywood, Anita E', 'Toms, Renin', 'Wood, James', 'Travis Waller, S', 'Raina MacIntyre, C']",Risk Anal,,,True
58a0c3ad6fd3ce5eae8b1199bd8e04ad8dadac81,PMC,Respiratory Tract Infections Due to Human Metapneumovirus in Immunocompromised Children,http://dx.doi.org/10.1093/jpids/piu100,PMC4240341,25419459,CC BY-NC-ND,"BACKGROUND: The clinical presentation and management of human metapneumovirus (hMPV) infections in immunocompromised children is not well understood. METHODS: We performed a retrospective evaluation of pediatric patients with laboratory-confirmed hMPV infections and underlying hematologic malignancy, solid tumors, solid organ transplant, rheumatologic disease, and/or receipt of chronic immunosuppressants. Data were analyzed using t tests and Fisher's exact tests. RESULTS: Overall, 55 patients (median age: 5 years; range: 5 months–19 years) with hMPV infection documented between 2006 and 2010 were identified, including 24 (44%) with hematologic malignancy, 9 (16%) undergoing hematopoietic stem cell transplant, 9 (16%) with solid tumors, and 8 (15%) with solid organ transplants. Three (5%) presented with fever alone, 35 (64%) presented with upper respiratory tract infections, and 16 (29%) presented with lower respiratory tract infections (LRTI). Twelve (23%) patients required intensive care unit admission and/or supplemental oxygen ≥28% FiO(2). Those with severe disease were more likely to be neutropenic (P = .02), but otherwise did not differ by age (P = .27), hematopoietic stem cell transplant recipient status (P = .19), or presence of lymphopenia (P = .09). Nine (16%) patients received treatment with ribavirin, intravenous immunoglobulin, or both. Three children (5%) died of hMPV pneumonia. CONCLUSIONS: Immunocompromised pediatric patients with hMPV infection have high rates of LRTI and mortality. The benefits of treatment with ribavirin and intravenous immunoglobulin in this patient population require further evaluation.",2014 Dec 21,"['Chu, Helen Y.', 'Renaud, Christian', 'Ficken, Elle', 'Thomson, Blythe', 'Kuypers, Jane', 'Englund, Janet A.']",J Pediatric Infect Dis Soc,,,True
5e2fc4aaa3045d5c12525483a0f18010601b015a,PMC,Mobile ECMO team for inter-hospital transportation of patients with ARDS: a retrospective case series,,PMC4246845,25436208,CC BY-NC,"INTRODUCTION: Transport of patients undergoing extracorporeal membrane oxygenation is currently available in 5 referral centers in our country. METHODS: Retrospective case series of patients managed by our mobile extracorporeal membrane oxygenation team and transferred to San Gerardo University Hospital from December 2004 to December 2012. RESULTS: 42 patients were transported. The mean age was 42.11 (standard deviation ±18.11) years, with a range between 2 years and 70. 14 patients were females (33%) and 28 males (67%). The average transport distance was 121.69 km (±183.08) with a range between 9 km and 1044 Km. The mission’s mean time was equal to 508 minutes (±185) with range of 120-960 minutes. 29 patients (69%) were transported with extracorporeal membrane oxygenation support, while 13 patients (31%) were transported with conventional ventilation. In 28 patients (97%) a veno-venous bypass was utilized, while in one case (3%) a Veno-Arterial cannulation was performed. 32 patients survived (76%) and have been discharged alive from hospital. No major clinical or technical issues were observed during the transport. CONCLUSIONS: According to our data, we conclude that a dedicated mobile team allowed safe ground transportation of patients with severe acute lung injury to our tertiary care institution.",2014,"['Lucchini, A', 'De Felippis, C', 'Elli, S', 'Gariboldi, R', 'Vimercati, S', 'Tundo, P', 'Bondi, H', 'Costa, M C']",Heart Lung Vessel,,,True
5d492015c79953419dd1cfc47ebf6b50297e0334,PMC,A novel method for synthetic vaccine construction based on protein assembly,http://dx.doi.org/10.1038/srep07266,PMC4248271,25434527,CC BY-NC-SA,"In the history of vaccine development, the synthetic vaccine is a milestone that is in stark contrast with traditional vaccines based on live-attenuated or inactivated microorganisms. Synthetic vaccines not only are safer than attenuated or inactivated microorganisms but also provide the opportunity for vaccine design for specific purposes. The first generation of synthetic vaccines has been largely based on DNA recombination technology and genetic manipulation. This de novo generation is occasionally time consuming and costly, especially in the era of genomics and when facing pandemic outbreaks of infectious diseases. To accelerate and simplify the R&D process for vaccines, we developed an improved method of synthetic vaccine construction based on protein assembly. We optimized and employed the recently developed SpyTag/SpyCatcher technique to establish a protein assembly system for vaccine generation from pre-prepared subunit proteins. As proof of principle, we chose a dendritic cell (DC)-targeting molecule and specific model antigens to generate desired vaccines. The results demonstrated that a new vaccine generated in this way does not hamper the individual function of different vaccine components and is efficient in inducing both T and B cell responses. This protein assembly strategy may be especially useful for high-throughput antigen screening or rapid vaccine generation.",2014 Dec 1,"['Liu, Zhida', 'Zhou, Hang', 'Wang, Wenjun', 'Tan, Wenjie', 'Fu, Yang-Xin', 'Zhu, Mingzhao']",Sci Rep,,,True
16d06c8b0afcba8080dcbc6739e3762b62a93025,PMC,A novel method for synthetic vaccine construction based on protein assembly,http://dx.doi.org/10.1038/srep07266,PMC4248271,25434527,CC BY-NC-SA,"In the history of vaccine development, the synthetic vaccine is a milestone that is in stark contrast with traditional vaccines based on live-attenuated or inactivated microorganisms. Synthetic vaccines not only are safer than attenuated or inactivated microorganisms but also provide the opportunity for vaccine design for specific purposes. The first generation of synthetic vaccines has been largely based on DNA recombination technology and genetic manipulation. This de novo generation is occasionally time consuming and costly, especially in the era of genomics and when facing pandemic outbreaks of infectious diseases. To accelerate and simplify the R&D process for vaccines, we developed an improved method of synthetic vaccine construction based on protein assembly. We optimized and employed the recently developed SpyTag/SpyCatcher technique to establish a protein assembly system for vaccine generation from pre-prepared subunit proteins. As proof of principle, we chose a dendritic cell (DC)-targeting molecule and specific model antigens to generate desired vaccines. The results demonstrated that a new vaccine generated in this way does not hamper the individual function of different vaccine components and is efficient in inducing both T and B cell responses. This protein assembly strategy may be especially useful for high-throughput antigen screening or rapid vaccine generation.",2014 Dec 1,"['Liu, Zhida', 'Zhou, Hang', 'Wang, Wenjun', 'Tan, Wenjie', 'Fu, Yang-Xin', 'Zhu, Mingzhao']",Sci Rep,,,False
6092602066323176223cd6d8deadfb8f689c0ea0,PMC,Re-emergent Human Adenovirus Genome Type 7d Caused an Acute Respiratory Disease Outbreak in Southern China After a Twenty-one Year Absence,http://dx.doi.org/10.1038/srep07365,PMC4258649,25482188,CC BY-NC-ND,"Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), among other illnesses. Of the ARD genotypes, HAdV-7 presents with more severe morbidity and higher mortality than the others. We report the isolation and identification of a genome type HAdV-7d (DG01_2011) from a recent outbreak in Southern China. Genome sequencing, phylogenetic analysis, and restriction endonuclease analysis (REA) comparisons with past pathogens indicate HAdV-7d has re-emerged in Southern China after an absence of twenty-one years. Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. DG01_2011 descends from both a strain circulating in Southwestern China (2010) and a strain from Shaanxi causing a fatality and outbreak (Northwestern China; 2009). Due to the higher morbidity and mortality rates associated with HAdV-7, the surveillance, identification, and characterization of these strains in population-dense China by REA and/or whole genome sequencing are strongly indicated. With these accurate identifications of specific HAdV types and an epidemiological database of regional HAdV pathogens, along with the HAdV genome stability noted across time and space, the development, availability, and deployment of appropriate vaccines are needed.",2014 Dec 8,"['Zhao, Suhui', 'Wan, Chengsong', 'Ke, Changwen', 'Seto, Jason', 'Dehghan, Shoaleh', 'Zou, Lirong', 'Zhou, Jie', 'Cheng, Zetao', 'Jing, Shuping', 'Zeng, Zhiwei', 'Zhang, Jing', 'Wan, Xuan', 'Wu, Xianbo', 'Zhao, Wei', 'Zhu, Li', 'Seto, Donald', 'Zhang, Qiwei']",Sci Rep,,,True
f46ad7149ec602bd131fd370682f1b73235cfacc,PMC,The Effectiveness of Convalescent Plasma and Hyperimmune Immunoglobulin for the Treatment of Severe Acute Respiratory Infections of Viral Etiology: A Systematic Review and Exploratory Meta-analysis,http://dx.doi.org/10.1093/infdis/jiu396,PMC4264590,25030060,CC BY-NC-ND,"Background. Administration of convalescent plasma, serum, or hyperimmune immunoglobulin may be of clinical benefit for treatment of severe acute respiratory infections (SARIs) of viral etiology. We conducted a systematic review and exploratory meta-analysis to assess the overall evidence. Methods. Healthcare databases and sources of grey literature were searched in July 2013. All records were screened against the protocol eligibility criteria, using a 3-stage process. Data extraction and risk of bias assessments were undertaken. Results. We identified 32 studies of SARS coronavirus infection and severe influenza. Narrative analyses revealed consistent evidence for a reduction in mortality, especially when convalescent plasma is administered early after symptom onset. Exploratory post hoc meta-analysis showed a statistically significant reduction in the pooled odds of mortality following treatment, compared with placebo or no therapy (odds ratio, 0.25; 95% confidence interval, .14–.45; I(2) = 0%). Studies were commonly of low or very low quality, lacked control groups, and at moderate or high risk of bias. Sources of clinical and methodological heterogeneity were identified. Conclusions. Convalescent plasma may reduce mortality and appears safe. This therapy should be studied within the context of a well-designed clinical trial or other formal evaluation, including for treatment of Middle East respiratory syndrome coronavirus CoV infection.",2015 Jan 1,"['Mair-Jenkins, John', 'Saavedra-Campos, Maria', 'Baillie, J. Kenneth', 'Cleary, Paul', 'Khaw, Fu-Meng', 'Lim, Wei Shen', 'Makki, Sophia', 'Rooney, Kevin D.', 'Beck, Charles R.', 'Nguyen-Van-Tam, Jonathan S.']",J Infect Dis,,,True
5aaa0dfb49b42f8fab7ce125f89360b828ee9298,PMC,"Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP)",http://dx.doi.org/10.1002/hep.26982,PMC4265264,24375637,CC BY-NC-ND,"Chronic hepatitis B virus (HBV) infection is a major public health problem worldwide. Although nucleos(t)ide analogs inhibiting viral reverse transcriptase are clinically available as anti-HBV agents, emergence of drug-resistant viruses highlights the need for new anti-HBV agents interfering with other targets. Here we report that cyclosporin A (CsA) can inhibit HBV entry into cultured hepatocytes. The anti-HBV effect of CsA was independent of binding to cyclophilin and calcineurin. Rather, blockade of HBV infection correlated with the ability to inhibit the transporter activity of sodium taurocholate cotransporting polypeptide (NTCP). We also found that HBV infection-susceptible cells, differentiated HepaRG cells and primary human hepatocytes expressed NTCP, while nonsusceptible cell lines did not. A series of compounds targeting NTCP could inhibit HBV infection. CsA inhibited the binding between NTCP and large envelope protein in vitro. Evaluation of CsA analogs identified a compound with higher anti-HBV potency, having a median inhibitory concentration <0.2 μM. Conclusion: This study provides a proof of concept for the novel strategy to identify anti-HBV agents by targeting the candidate HBV receptor, NTCP, using CsA as a structural platform. (Hepatology 2014;59:1726–1737)",2014 May 1,"['Watashi, Koichi', 'Sluder, Ann', 'Daito, Takuji', 'Matsunaga, Satoko', 'Ryo, Akihide', 'Nagamori, Shushi', 'Iwamoto, Masashi', 'Nakajima, Syo', 'Tsukuda, Senko', 'Borroto-Esoda, Katyna', 'Sugiyama, Masaya', 'Tanaka, Yasuhito', 'Kanai, Yoshikatsu', 'Kusuhara, Hiroyuki', 'Mizokami, Masashi', 'Wakita, Takaji']",Hepatology,,,True
b7573a8e8c03ee3851379dd2527a853ac7f92508,PMC,"Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP)",http://dx.doi.org/10.1002/hep.26982,PMC4265264,24375637,CC BY-NC-ND,"Chronic hepatitis B virus (HBV) infection is a major public health problem worldwide. Although nucleos(t)ide analogs inhibiting viral reverse transcriptase are clinically available as anti-HBV agents, emergence of drug-resistant viruses highlights the need for new anti-HBV agents interfering with other targets. Here we report that cyclosporin A (CsA) can inhibit HBV entry into cultured hepatocytes. The anti-HBV effect of CsA was independent of binding to cyclophilin and calcineurin. Rather, blockade of HBV infection correlated with the ability to inhibit the transporter activity of sodium taurocholate cotransporting polypeptide (NTCP). We also found that HBV infection-susceptible cells, differentiated HepaRG cells and primary human hepatocytes expressed NTCP, while nonsusceptible cell lines did not. A series of compounds targeting NTCP could inhibit HBV infection. CsA inhibited the binding between NTCP and large envelope protein in vitro. Evaluation of CsA analogs identified a compound with higher anti-HBV potency, having a median inhibitory concentration <0.2 μM. Conclusion: This study provides a proof of concept for the novel strategy to identify anti-HBV agents by targeting the candidate HBV receptor, NTCP, using CsA as a structural platform. (Hepatology 2014;59:1726–1737)",2014 May 1,"['Watashi, Koichi', 'Sluder, Ann', 'Daito, Takuji', 'Matsunaga, Satoko', 'Ryo, Akihide', 'Nagamori, Shushi', 'Iwamoto, Masashi', 'Nakajima, Syo', 'Tsukuda, Senko', 'Borroto-Esoda, Katyna', 'Sugiyama, Masaya', 'Tanaka, Yasuhito', 'Kanai, Yoshikatsu', 'Kusuhara, Hiroyuki', 'Mizokami, Masashi', 'Wakita, Takaji']",Hepatology,,,True
f876b5a87961cd555b5d7a70fc52286e23ed2bcc,PMC,Transmissibility of the Ice Bucket Challenge among globally influential celebrities: retrospective cohort study,http://dx.doi.org/10.1136/bmj.g7185,PMC4267700,25514905,CC BY-NC,"Objectives To estimate the transmissibility of the Ice Bucket Challenge among globally influential celebrities and to identify associated risk factors. Design Retrospective cohort study. Setting Social media (YouTube, Facebook, Twitter, Instagram). Participants David Beckham, Cristiano Ronaldo, Benedict Cumberbatch, Stephen Hawking, Mark Zuckerberg, Oprah Winfrey, Homer Simpson, and Kermit the Frog were defined as index cases. We included contacts up to the fifth generation seeded from each index case and enrolled a total of 99 participants into the cohort. Main outcome measures Basic reproduction number R(0), serial interval of accepting the challenge, and odds ratios of associated risk factors based on fully observed nomination chains; R(0 )is a measure of transmissibility and is defined as the number of secondary cases generated by a single index in a fully susceptible population. Serial interval is the duration between onset of a primary case and onset of its secondary cases. Results Based on the empirical data and assuming a branching process we estimated a mean R(0) of 1.43 (95% confidence interval 1.23 to 1.65) and a mean serial interval for accepting the challenge of 2.1 days (median 1 day). Higher log (base 10) net worth of the participants was positively associated with transmission (odds ratio 1.63, 95% confidence interval 1.06 to 2.50), adjusting for age and sex. Conclusions The Ice Bucket Challenge was moderately transmissible among a group of globally influential celebrities, in the range of the pandemic A/H1N1 2009 influenza. The challenge was more likely to be spread by richer celebrities, perhaps in part reflecting greater social influence.",2014 Dec 16,"['Ni, Michael Y', 'Chan, Brandford H Y', 'Leung, Gabriel M', 'Lau, Eric H Y', 'Pang, Herbert']",BMJ,,,False
5308e5cb92ff0ef7f39100215505a503bdeb1311,PMC,Transmissibility of the Ice Bucket Challenge among globally influential celebrities: retrospective cohort study,http://dx.doi.org/10.1136/bmj.g7185,PMC4267700,25514905,CC BY-NC,"Objectives To estimate the transmissibility of the Ice Bucket Challenge among globally influential celebrities and to identify associated risk factors. Design Retrospective cohort study. Setting Social media (YouTube, Facebook, Twitter, Instagram). Participants David Beckham, Cristiano Ronaldo, Benedict Cumberbatch, Stephen Hawking, Mark Zuckerberg, Oprah Winfrey, Homer Simpson, and Kermit the Frog were defined as index cases. We included contacts up to the fifth generation seeded from each index case and enrolled a total of 99 participants into the cohort. Main outcome measures Basic reproduction number R(0), serial interval of accepting the challenge, and odds ratios of associated risk factors based on fully observed nomination chains; R(0 )is a measure of transmissibility and is defined as the number of secondary cases generated by a single index in a fully susceptible population. Serial interval is the duration between onset of a primary case and onset of its secondary cases. Results Based on the empirical data and assuming a branching process we estimated a mean R(0) of 1.43 (95% confidence interval 1.23 to 1.65) and a mean serial interval for accepting the challenge of 2.1 days (median 1 day). Higher log (base 10) net worth of the participants was positively associated with transmission (odds ratio 1.63, 95% confidence interval 1.06 to 2.50), adjusting for age and sex. Conclusions The Ice Bucket Challenge was moderately transmissible among a group of globally influential celebrities, in the range of the pandemic A/H1N1 2009 influenza. The challenge was more likely to be spread by richer celebrities, perhaps in part reflecting greater social influence.",2014 Dec 16,"['Ni, Michael Y', 'Chan, Brandford H Y', 'Leung, Gabriel M', 'Lau, Eric H Y', 'Pang, Herbert']",BMJ,,,False
824e4aebd39a0531625542fb7328917bb061e5a4,PMC,Molecular pathology of emerging coronavirus infections,http://dx.doi.org/10.1002/path.4454,PMC4267971,25270030,CC BY-NC-ND,"Respiratory viruses can cause a wide spectrum of pulmonary diseases, ranging from mild, upper respiratory tract infections to severe and life-threatening lower respiratory tract infections, including the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Viral clearance and subsequent recovery from infection require activation of an effective host immune response; however, many immune effector cells may also cause injury to host tissues. Severe acute respiratory syndrome (SARS) coronavirus and Middle East respiratory syndrome (MERS) coronavirus cause severe infection of the lower respiratory tract, with 10% and 35% overall mortality rates, respectively; however, >50% mortality rates are seen in the aged and immunosuppressed populations. While these viruses are susceptible to interferon treatment in vitro, they both encode numerous genes that allow for successful evasion of the host immune system until after high virus titres have been achieved. In this review, we discuss the importance of the innate immune response and the development of lung pathology following human coronavirus infection.",2015 Jan 11,"['Gralinski, Lisa E', 'Baric, Ralph S']",J Pathol,,,True
4fd25cc19b106e5c8a69f89162ca37719192330d,PMC,Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients (allogeneic SCT excluded): updated guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)(†),http://dx.doi.org/10.1093/annonc/mdu192,PMC4269340,24833776,CC BY-NC,"Up to 25% of patients with profound neutropenia lasting for >10 days develop lung infiltrates, which frequently do not respond to broad-spectrum antibacterial therapy. While a causative pathogen remains undetected in the majority of cases, Aspergillus spp., Pneumocystis jirovecii, multi-resistant Gram-negative pathogens, mycobacteria or respiratory viruses may be involved. In at-risk patients who have received trimethoprim–sulfamethoxazole (TMP/SMX) prophylaxis, filamentous fungal pathogens appear to be predominant, yet commonly not proven at the time of treatment initiation. Pathogens isolated from blood cultures, bronchoalveolar lavage (BAL) or respiratory secretions are not always relevant for the etiology of pulmonary infiltrates and should therefore be interpreted critically. Laboratory tests for detecting Aspergillus galactomannan, β-d-glucan or DNA from blood, BAL or tissue samples may facilitate the diagnosis; however, most polymerase chain reaction assays are not yet standardized and validated. Apart from infectious agents, pulmonary side-effects from cytotoxic drugs, radiotherapy or pulmonary involvement by the underlying malignancy should be included into differential diagnosis and eventually be clarified by invasive diagnostic procedures. Pre-emptive treatment with mold-active systemic antifungal agents improves clinical outcome, while other microorganisms are preferably treated only when microbiologically documented. High-dose TMP/SMX is first choice for treatment of Pneumocystis pneumonia, while cytomegalovirus pneumonia is treated primarily with ganciclovir or foscarnet in most patients. In a considerable number of patients, clinical outcome may be favorable despite respiratory failure, so that intensive care should be unrestrictedly provided in patients whose prognosis is not desperate due to other reasons.",2015 Jan 15,"['Maschmeyer, G.', 'Carratalà, J.', 'Buchheidt, D.', 'Hamprecht, A.', 'Heussel, C. P.', 'Kahl, C.', 'Lorenz, J.', 'Neumann, S.', 'Rieger, C.', 'Ruhnke, M.', 'Salwender, H.', 'Schmidt-Hieber, M.', 'Azoulay, E.']",Ann Oncol,,,True
1f8144c7b80bb22a8af2478791657d4cbaa8d802,PMC,M gene analysis of canine coronavirus strains detected in Korea,http://dx.doi.org/10.4142/jvs.2014.15.4.495,PMC4269591,25234323,CC BY-NC,"The purpose of this study was to investigate the genetic features of canine coronavirus (CCV) strains detected in Korea. M gene sequences obtained for isolates from 22 dogs with enteritis over a 5-year period were evaluated. Sequence comparison revealed that the 22 Korean CCV strains had an 87.2 to 100% nucleotide homology. Comparing to the typical reference CCV strains (type II), the nucleotide sequence of Korean strains had homology ranged from 86.3% to 98.3% (89.1% to 99.2% for the amino acid sequence) and 87.7% to 97.8% (92.4% to 100% for the amino acid sequence) when compared to FCoV-like CCV strains (type I). Three amino acid variations in the M gene were characteristic for the Korean CCV strains. Phylogenetic analysis demonstrated that the 22 Korean CCV strains belonged to four typical CCV clusters (i.e., a unique Korean CCV cluster, a type II and transmissible gastroenteritis virus cluster, an intermediate cluster between type I and II, and a type I cluster). This study was the first to identify genetic differences of the M gene from Korean CCV strains and provided a platform for molecular identification of different Korean CCV strains.",2014 Dec 15,"['Jeoung, Seok-Young', 'Ann, So-Yun', 'Kim, Hyun-Tae', 'Kim, Doo']",J Vet Sci,,,True
3f1cfb6b5432c28ba97e2c1fbb8ca341c35f6b4e,PMC,Moratorium on Research Intended To Create Novel Potential Pandemic Pathogens,http://dx.doi.org/10.1128/mBio.02366-14,PMC4271556,25505122,CC BY-NC-SA,,2014 Dec 12,"['Lipsitch, Marc', 'Inglesby, Thomas V.']",mBio,,,True
d8b4bb30789355b295394864873228a15c4868b3,PMC,Falling down the Rabbit Hole: aTRIP Toward Lexiconic Precision in the “Gain-of-Function” Debate,http://dx.doi.org/10.1128/mBio.02421-14,PMC4271557,25505123,CC BY-NC-SA,,2014 Dec 12,"['Duprex, W. Paul', 'Casadevall, Arturo']",mBio,,,True
f2659697647ee6bef684444c4bc46b433b51ef76,PMC,mBio Addresses the Pause in Gain-of-Function (GOF) Experiments Involving Pathogens with Pandemic Potential (PPP),http://dx.doi.org/10.1128/mBio.02434-14,PMC4271558,25505126,CC BY-NC-SA,,2014 Dec 12,"['Casadevall, Arturo', 'Shenk, Thomas']",mBio,,,True
5e8abc62533a447422d5ead64d4ae4991cc99052,PMC,"Xyloketal B, a marine compound, acts on a network of molecular proteins and regulates the activity and expression of rat cytochrome P450 3a: a bioinformatic and animal study",http://dx.doi.org/10.2147/DDDT.S73476,PMC4271727,25548518,CC BY-NC,"Natural compounds are becoming popular for the treatment of illnesses and health promotion, but the mechanisms of action and safety profiles are often unknown. Xyloketal B (XKB) is a novel marine compound isolated from the mangrove fungus Xylaria sp., with potent antioxidative, neuroprotective, and cardioprotective effects. However, its molecular targets and effects on drug-metabolizing enzymes are unknown. This study aimed to investigate the potential molecular targets of XKB using bioinformatic approaches and to examine the effect of XKB on the expression and activity of rat cytochrome P450 3a (Cyp3a) subfamily members using midazolam as a model probe. DDI-CPI, a server that can predict drug–drug interactions via the chemical–protein interactome, was employed to predict the targets of XKB, and the Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to analyze the pathways of the predicted targets of XKB. Homology modeling was performed using the Discovery Studio program 3.1. The activity and expression of rat hepatic Cyp3a were examined after the rats were treated with XKB at 7 and 14 mg/kg for 8 consecutive days. Rat plasma concentrations of midazolam and its metabolite 1′-OH-midazolam were determined using a validated high-performance liquid chromatographic method. Bioinformatic analysis showed that there were over 324 functional proteins and 61 related signaling pathways that were potentially regulated by XKB. A molecular docking study showed that XKB bound to the active site of human cytochrome P450 3A4 and rat Cyp3a2 homology model via the formation of hydrogen bonds. The in vivo study showed that oral administration of XKB at 14 mg/kg to rats for 8 days significantly increased the area under the plasma concentration-time curve (AUC) of midazolam, with a concomitant decrease in the plasma clearance and AUC ratio of 1′-OH-midazolam over midazolam. Further, oral administration of 14 mg/kg XKB for 8 days markedly reduced the activity and expression of hepatic Cyp3a in rats. Taken together, the results show that XKB could regulate networks of molecular proteins and related signaling pathways and that XKB downregulated hepatic Cyp3a in rats. XKB might cause drug interactions through modulation of the activity and expression of Cyp3a members. More studies are warranted to confirm the mechanisms of action of XKB and to investigate the underlying mechanism for the regulating effect of XKB on Cyp3a subfamily members.",2014 Dec 12,"['Su, Junhui', 'Chang, Cui', 'Xiang, Qi', 'Zhou, Zhi-Wei', 'Luo, Rong', 'Yang, Lun', 'He, Zhi-Xu', 'Yang, Hongtu', 'Li, Jianan', 'Bei, Yu', 'Xu, Jinmei', 'Zhang, Minjing', 'Zhang, Qihao', 'Su, Zhijian', 'Huang, Yadong', 'Pang, Jiyan', 'Zhou, Shu-Feng']",Drug Des Devel Ther,,,True
f510e7651315b8a000b2271107451ba284f10292,PMC,Chemical and Biological Mechanisms of Pathogen Reduction Technologies,http://dx.doi.org/10.1111/php.12311,PMC4277684,25041351,CC BY-NC,"Within the last decade new technologies have been developed and implemented which employ light, often in the presence of a photosensitizer, to inactivate pathogens that reside in human blood products for the purpose of transfusion. These pathogen reduction technologies attempt to find the proper balance between pathogen kill and cell quality. Each system utilizes various chemistries that not only impact which pathogens they can inactivate and how, but also how the treatments affect the plasma and cellular proteins and to what degree. This paper aims to present the various chemical mechanisms for pathogen reduction in transfusion medicine that are currently practiced or in development.",2014 Sep 20,"['Mundt, Janna M', 'Rouse, Lindsay', 'Van den Bossche, Jeroen', 'Goodrich, Raymond P']",Photochem Photobiol,,,True
a81c646c5838cf678fd22a7527e88f964bcbb862,PMC,"Vagueness and Costs of the Pause on Gain-of-Function (GOF) Experiments on Pathogens with Pandemic Potential, Including Influenza Virus",http://dx.doi.org/10.1128/mBio.02292-14,PMC4278541,25505121,CC BY-NC-SA,,2014 Dec 12,"['Imperiale, Michael J.', 'Casadevall, Arturo']",mBio,,,True
8dd1202c8cda0d3a3859c3346cfbc6647317b4f3,PMC,Use of Highly Pathogenic Avian Influenza A(H5N1) Gain-Of-Function Studies for Molecular-Based Surveillance and Pandemic Preparedness,http://dx.doi.org/10.1128/mBio.02431-14,PMC4278543,25505125,CC BY-NC-SA,,2014 Dec 12,"['Davis, C. Todd', 'Chen, Li-Mei', 'Pappas, Claudia', 'Stevens, James', 'Tumpey, Terrence M.', 'Gubareva, Larisa V.', 'Katz, Jacqueline M.', 'Villanueva, Julie M.', 'Donis, Ruben O.', 'Cox, Nancy J.']",mBio,,,True
3b5c43f1068e79db27adaca5df0bd717851c37cc,PMC,Pathway and Network Approaches for Identification of Cancer Signature Markers from Omics Data,http://dx.doi.org/10.7150/jca.10631,PMC4278915,25553089,CC BY-NC-ND,"The advancement of high throughput omic technologies during the past few years has made it possible to perform many complex assays in a much shorter time than the traditional approaches. The rapid accumulation and wide availability of omic data generated by these technologies offer great opportunities to unravel disease mechanisms, but also presents significant challenges to extract knowledge from such massive data and to evaluate the findings. To address these challenges, a number of pathway and network based approaches have been introduced. This review article evaluates these methods and discusses their application in cancer biomarker discovery using hepatocellular carcinoma (HCC) as an example.",2015 Jan 1,"['Wang, Jinlian', 'Zuo, Yiming', 'Man, Yan-gao', 'Avital, Itzhak', 'Stojadinovic, Alexander', 'Liu, Meng', 'Yang, Xiaowei', 'Varghese, Rency S.', 'Tadesse, Mahlet G', 'Ressom, Habtom W']",J Cancer,,,True
b71a289c291ad516b7990a8582c1fece5330e5f5,PMC,"Toxocariasis After Slug Ingestion Characterized by Severe Neurologic, Ocular, and Pulmonary Involvement",http://dx.doi.org/10.1093/ofid/ofu063,PMC4281794,25734133,CC BY-NC-ND,"Human toxocariasis is generally a benign, self-curing disease, and neurologic involvement is quite exceptional. In this study, we report a case of toxocariasis caused by ingestion of an unusual transport host, namely live slugs. The clinical picture comprised eosinophilic lung involvement with severe neurologic disorders in relation to vasculitis as well as retinal detachment.",2014 Aug 11,"['Fellrath, Jean-Marc', 'Magnaval, Jean-François']",Open Forum Infect Dis,,,True
9f82db8107ec9ced3f686b30ccc27645cd6f9643,PMC,Other Respiratory Viruses Are Important Contributors to Adult Respiratory Hospitalizations and Mortality Even During Peak Weeks of the Influenza Season,http://dx.doi.org/10.1093/ofid/ofu086,PMC4281811,25734152,CC BY-NC-ND,"BACKGROUND:  During peak weeks of seasonal influenza epidemics, severe respiratory infections without laboratory confirmation are typically attributed to influenza. METHODS:  In this prospective study, specimens and demographic and clinical data were collected from adults admitted with respiratory symptoms to 4 hospitals during the 8–10 peak weeks of 2 influenza seasons. Specimens were systematically tested for influenza and 13 other respiratory viruses (ORVs) by using the Luminex RVP FAST assay. RESULTS:  At least 1 respiratory virus was identified in 46% (21% influenza, 25% noninfluenza; 2% coinfection) of the 286 enrolled patients in 2011–2012 and in 62% (46% influenza, 16% noninfluenza; 3% coinfection) of the 396 enrolled patients in 2012–2013. Among patients aged ≥75 years, twice as many ORVs (32%) as influenza viruses (14%) were detected in 2011–2012. During both seasons, the most frequently detected ORVs were enteroviruses/rhinoviruses (7%), respiratory syncytial virus (6%), human metapneumovirus (5%), coronaviruses (4%), and parainfluenza viruses (2%). Disease severity was similar for influenza and ORVs during both seasons. CONCLUSIONS:  Although ORV contribution relative to influenza varies by age and season, during the peak weeks of certain influenza seasons, ORVs may be a more frequent cause of elderly hospitalization than influenza.",2014 Sep 22,"['Gilca, Rodica', 'Amini, Rachid', 'Douville-Fradet, Monique', 'Charest, Hugues', 'Dubuque, Josée', 'Boulianne, Nicole', 'Skowronski, Danuta M.', 'De Serres, Gaston']",Open Forum Infect Dis,,,True
9521353cc7ef3d0734d76453622762532f06f777,PMC,Investigation into the Role of Potentially Contaminated Feed as a Source of the First-Detected Outbreaks of Porcine Epidemic Diarrhea in Canada,http://dx.doi.org/10.1111/tbed.12269,PMC4282400,25098383,CC BY-NC-ND,"SUMMARY: In January 2014, approximately 9 months following the initial detection of porcine epidemic diarrhea (PED) in the USA, the first case of PED was confirmed in a swine herd in south-western Ontario. A follow-up epidemiological investigation carried out on the initial and 10 subsequent Ontario PED cases pointed to feed as a common risk factor. As a result, several lots of feed and spray-dried porcine plasma (SDPP) used as a feed supplement were tested for the presence of PEDV genome by real-time RT-PCR assay. Several of these tested positive, supporting the notion that contaminated feed may have been responsible for the introduction of PEDV into Canada. These findings led us to conduct a bioassay experiment in which three PEDV-positive SDPP samples (from a single lot) and two PEDV-positive feed samples supplemented with this SDPP were used to orally inoculate 3-week-old piglets. Although the feed-inoculated piglets did not show any significant excretion of PEDV, the SDPP-inoculated piglets shed PEDV at a relatively high level for ≥9 days. Despite the fact that the tested PEDV genome positive feed did not result in obvious piglet infection in our bioassay experiment, contaminated feed cannot be ruled out as a likely source of this introduction in the field where many other variables may play a contributing role.",2014 Oct 7,"['Pasick, J', 'Berhane, Y', 'Ojkic, D', 'Maxie, G', 'Embury-Hyatt, C', 'Swekla, K', 'Handel, K', 'Fairles, J', 'Alexandersen, S']",Transbound Emerg Dis,,,True
8cc42c8dc091b1f9333ff2b66604d54e5fc021c4,PMC,"The history of monoclonal antibody development – Progress, remaining challenges and future innovations",http://dx.doi.org/10.1016/j.amsu.2014.09.001,PMC4284445,25568796,CC BY-NC-SA,"As medicine progresses into a new era of personalised therapy, the use of monoclonal antibodies to treat a wide range of diseases lies at the heart of this new forefront. Since the licencing of the first monoclonal antibody for clinical use 30 years ago, the monoclonal antibody industry has expanded exponentially and is now valued at billions of dollars. With major advances in genetic sequencing and biomedical research, much research into monoclonal antibodies now focuses on identifying new targets for development and maximising their efficacy for use in clinical practice. However, a balance has to be struck with regards to reducing numbers of side-effects and overall economic cost, which arguably somewhat blighted their early clinical and commercial successes. Nowadays, there are approximately 30 monoclonal antibodies that have been approved for use in clinical practice with many more currently being tested in clinical trials. Some of the current major limitations include: the use of inefficient models for generation, a lack of efficacy and issues of cost-effectiveness. Some of the current research focuses on ways to improve the efficacy of existing monoclonal antibodies through optimising their effects and the addition of beneficial modifications. This review will focus on the history of monoclonal antibody development – how it has increasingly moved away from using laborious animal models to a more effective phage display system, some of the major drawbacks from a clinical and economical point of view and future innovations that are currently being researched to maximise their effectiveness for future clinical use.",2014 Sep 11,"Liu, Justin K.H.",Ann Med Surg (Lond),,,False
c9fc9152d225265c48f4b8023ffab0a26de38132,PMC,"Enhanced-Transient Expression of Hepatitis C Virus Core Protein in Nicotiana tabacum, a Protein With Potential Clinical Applications",http://dx.doi.org/10.5812/hepatmon.20524,PMC4286711,25598788,CC BY-NC,"BACKGROUND: Hepatitis C virus (HCV) is major cause of liver cirrhosis in humans. HCV capsid (core) protein (HCVcp) is a highly demanded antigen for various diagnostic, immunization and pathogenesis studies. Plants are considered as an expression system for producing safe and inexpensive biopharmaceutical proteins. Although invention of transgenic (stable) tobacco plants expressing HCVcp with proper antigenic properties was recently reported, no data for “transient-expression” that is currently the method of choice for rapid, simple and lower-priced protein expression in plants is available for HCVcp. OBJECTIVES: The purpose of this study was to design a highly codon-optimized HCVcp gene for construction of an efficient transient-plant expression system for production of HCVcp with proper antigenic properties in a regional tobacco plant (Iranian Jafarabadi-cultivar) by evaluation of different classes of vectors and suppression of gene-silencing in tobacco. MATERIALS AND METHODS: A codon-optimized gene encoding the Kozak sequence, 6xHis-tag, HCVcp (1-122) and KDEL peptide in tandem (from N- to C-terminal) was designed and inserted into potato virus-X (PVX) and classic pBI121 binary vectors in separate cloning reactions. The resulted recombinant plasmids were transferred into Agrobacterium tumefaciens and vacuum infiltrated into tobacco leaves. The effect of gene silencing suppressor P19 protein derived from tomato bushy stunt virus on the expression yield of HCVcp by each construct was also evaluated by co-infiltration in separate groups. The expressed HCVcp was evaluated by dot and western blotting and ELISA assays. RESULTS: The codon-optimized gene had an increased adaptation index value (from 0.65 to 0.85) and reduced GC content (from 62.62 to 51.05) in tobacco and removed the possible deleterious effect of “GGTAAG” splice site in native HCVcp. Blotting assays via specific antibodies confirmed the expression of the 15 kDa HCVcp. The expression level of HCVcp was enhanced by 4-5 times in P19 co-agroinfiltrated plants with better outcomes for PVX, compared to pBI121 vector (0.022% versus 0.019% of the total soluble protein). The plant-derived HCVcp (pHCVcp) could properly identify the HCVcp antibody in HCV-infected human sera compared to Escherichia coli-derived HCVcp (eHCVcp), indicating its potential for diagnostic/immunization applications. CONCLUSIONS: By employment of gene optimization strategies, use of viral-based vectors and suppression of plant-derived gene silencing effect, efficient transient expression of HCVcp in tobacco with proper antigenic properties could be possible.",2014 Nov 24,"['Mohammadzadeh, Sara', 'Khabiri, Alireza', 'Roohvand, Farzin', 'Memarnejadian, Arash', 'Salmanian, Ali Hatef', 'Ajdary, Soheila', 'Ehsani, Parastoo']",Hepat Mon,,,True
b90c4861f039ec80e7b92f2da68546107e8152f3,PMC,Crowning Proteins: Modulating the Protein Surface Properties using Crown Ethers**,http://dx.doi.org/10.1002/anie.201405664,PMC4288931,25287606,CC BY-NC,"Crown ethers are small, cyclic polyethers that have found wide-spread use in phase-transfer catalysis and, to a certain degree, in protein chemistry. Crown ethers readily bind metallic and organic cations, including positively charged amino acid side chains. We elucidated the crystal structures of several protein-crown ether co-crystals grown in the presence of 18-crown-6. We then employed biophysical methods and molecular dynamics simulations to compare these complexes with the corresponding apoproteins and with similar complexes with ring-shaped low-molecular-weight polyethylene glycols. Our studies show that crown ethers can modify protein surface behavior dramatically by stabilizing either intra- or intermolecular interactions. Consequently, we propose that crown ethers can be used to modulate a wide variety of protein surface behaviors, such as oligomerization, domain–domain interactions, stabilization in organic solvents, and crystallization.",2014 Nov 24,"['Lee, Cheng-Chung', 'Maestre-Reyna, Manuel', 'Hsu, Kai-Cheng', 'Wang, Hao-Ching', 'Liu, Chia-I', 'Jeng, Wen-Yih', 'Lin, Li-Ling', 'Wood, Richard', 'Chou, Chia-Cheng', 'Yang, Jinn-Moon', 'Wang, Andrew H-J']",Angew Chem Int Ed Engl,,,False
a559e323cc2f1aaa14ae90f386f079163e2401aa,PMC,Crowning Proteins: Modulating the Protein Surface Properties using Crown Ethers**,http://dx.doi.org/10.1002/anie.201405664,PMC4288931,25287606,CC BY-NC,"Crown ethers are small, cyclic polyethers that have found wide-spread use in phase-transfer catalysis and, to a certain degree, in protein chemistry. Crown ethers readily bind metallic and organic cations, including positively charged amino acid side chains. We elucidated the crystal structures of several protein-crown ether co-crystals grown in the presence of 18-crown-6. We then employed biophysical methods and molecular dynamics simulations to compare these complexes with the corresponding apoproteins and with similar complexes with ring-shaped low-molecular-weight polyethylene glycols. Our studies show that crown ethers can modify protein surface behavior dramatically by stabilizing either intra- or intermolecular interactions. Consequently, we propose that crown ethers can be used to modulate a wide variety of protein surface behaviors, such as oligomerization, domain–domain interactions, stabilization in organic solvents, and crystallization.",2014 Nov 24,"['Lee, Cheng-Chung', 'Maestre-Reyna, Manuel', 'Hsu, Kai-Cheng', 'Wang, Hao-Ching', 'Liu, Chia-I', 'Jeng, Wen-Yih', 'Lin, Li-Ling', 'Wood, Richard', 'Chou, Chia-Cheng', 'Yang, Jinn-Moon', 'Wang, Andrew H-J']",Angew Chem Int Ed Engl,,,True
2b36f467dee97f9675e187cabd4e4585e7ab17f2,PMC,Developing a vaccine for human rhinoviruses,http://dx.doi.org/10.14312/2053-1273.2014-3,PMC4291752,25593706,CC BY-NC,"Rhinoviruses (RV’s) are common human pathogens of the respiratory tract being the most frequent cause of mild diseases of the upper respiratory tract (common cold) but more importantly they are a major initiator of acute exacerbations of chronic airway diseases. Infections can be life threatening in the latter context however RV -induced common colds have an associated economic cost from loss of productivity due to absence from work or school. There are no appropriate antiviral therapies available and vaccine strategies have failed because of the large number of viral serotypes and the lack of cross-serotype protection generated. Here, approaches past and present for development of a vaccine to these widespread human pathogens are highlighted.",2014 Oct 1,"McLean, Gary R",J Vaccines Immun,,,True
bf87996bb6c0dbed5de9512ac2bab800417a8956,PMC,Identification of highly conserved regions in L-segment of Crimean–Congo hemorrhagic fever virus and immunoinformatic prediction about potential novel vaccine,http://dx.doi.org/10.2147/AABC.S75250,PMC4293217,25609983,CC BY-NC,"Crimean–Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic viral disease with a disease fatality rate between 15% and 70%. Despite the wide range of distribution, the virus (CCHFV) is basically endemic in Africa, Asia, eastern Europe, and the Middle East. Acute febrile illness associated with petechiae, disseminated intravascular coagulation, and multiple-organ failure are the main symptoms of the disease. With all these fatal effects, CCHFV is considered a huge threat as no successful therapeutic approach is currently available for the treatment of this disease. In the present study, we have used the immunoinformatics approach to design a potential epitope-based vaccine against the RNA-dependent RNA polymerase-L of CCHFV. Both the T-cell and B-cell epitopes were assessed, and the epitope “DCSSTPPDR” was found to be the most potential one, with 100% conservancy among all the strains of CCHFV. The epitope was also found to interact with both type I and II major histocompatibility complex molecules and is considered nonallergenic as well. In vivo study of our proposed peptide is advised for novel universal vaccine production, which might be an effective path to prevent CCHF disease.",2015 Jan 8,"['Oany, Arafat Rahman', 'Ahmad, Shah Adil Ishtiyaq', 'Hossain, Mohammad Uzzal', 'Jyoti, Tahmina Pervin']",Adv Appl Bioinform Chem,,,True
0eed9647904ba87a841a177c12a0238faf5c2bd0,PMC,Utilization of the respiratory virus multiplex reverse transcription-polymerase chain reaction test for adult patients at a Korean tertiary care center,http://dx.doi.org/10.3904/kjim.2015.30.1.96,PMC4293570,25589841,CC BY-NC,"BACKGROUND/AIMS: Respiratory viruses (RVs) are considered to be important respiratory pathogens in adult patients, and the multiplex reverse transcription-polymerase chain reaction (RT-PCR) test is used frequently in adult patients with respiratory infections. However, clinical data regarding utilization of the multiplex RT-PCR test for RVs are lacking. METHODS: We investigated the utilization of the multiplex RT-PCR test for RVs at Chung-Ang University Hospital in Seoul, Korea, between January 2012 and April 2013. RESULTS: During the study period, the multiplex RT-PCR test was performed for 291 adult patients. The test frequency was 4.9% of rapid influenza antigen detection tests and 0.8% of respiratory bacterial culture studies. A turnaround time of < 48 hours was observed in 25.9% of positive tests. Most of the tests were performed for admitted patients (97.9%) with a community-acquired infection (84.2%) during the flu season (82.5%). RVs were detected in 81 of 291 cases (27.8%). The RV positivity rates for community- and hospital-acquired infections did not differ (28.6% vs. 23.9%, p = 0.52). Of 166 patients with pneumonia, 44 (26.5%) had a viral infection. Among the patients with RV-associated pneumonia, an RV other than influenza was detected in 20 patients (45.4%). CONCLUSIONS: The multiplex RT-PCR test for RVs was infrequently performed at a tertiary care center, and the test results were often reported late. The test was most often performed for admitted adult patients with community-acquired infections during the flu season. The utilization of multiplex RT-PCR testing for RVs in current clinical practice should be improved.",2015 Jan 30,"['Ahn, Mi Young', 'Choi, Seong-Ho', 'Chung, Jin-Won', 'Kim, Hye Ryoun']",Korean J Intern Med,,,True
a0b5cb01c765429c9f82a74d5822f2cd6ec5dcaa,PMC,Unequivocal glycyrrhizin isomer determination and comparative in vitro bioactivities of root extracts in four Glycyrrhiza species,http://dx.doi.org/10.1016/j.jare.2014.05.001,PMC4293670,25685548,CC BY-NC-ND,"Glycyrrhiza glabra, commonly known as licorice, is a popular herbal supplement used for the treatment of chronic inflammatory conditions and as sweetener in the food industry. This species contains a myriad of phytochemicals including the major saponin glycoside glycyrrhizin (G) of Glycyrrhetinic acid (GA) aglycone. In this study, 2D-ROESY NMR technique was successfully applied for distinguishing 18α and 18β glycyrrhetinic acid (GA). ROESY spectra acquired from G. glabra, Glycyrrhiza uralensis and Glycyrrhiza inflata crude extracts revealed the presence of G in its β-form. Anti-inflammatory activity of four Glycyrrhiza species, G, glabra, G. uralensis, G. inflata, and G. echinata roots was assessed against COX-1 inhibition revealing that phenolics rather than glycyrrhizin are biologically active in this assay. G. inflata exhibits a strong cytotoxic effect against PC3 and HT29 cells lines, whereas other species are inactive. This study presents an effective NMR method for G isomer assignment in licorice extracts that does not require any preliminary chromatography or any other purification step.",2015 Jan 14,"['Farag, Mohamed A.', 'Porzel, Andrea', 'Wessjohann, Ludger A.']",J Adv Res,,,False
87b8b85391605bcd1b6c7ddaf1189b3229db4e06,PMC,Media impact switching surface during an infectious disease outbreak,http://dx.doi.org/10.1038/srep07838,PMC4296304,25592757,CC BY-NC-ND,"There are many challenges to quantifying and evaluating the media impact on the control of emerging infectious diseases. We modeled such media impacts using a piecewise smooth function depending on both the case number and its rate of change. The proposed model was then converted into a switching system, with the switching surface determined by a functional relationship between susceptible populations and different subgroups of infectives. By parameterizing the proposed model with the 2009 A/H1N1 influenza outbreak data in the Shaanxi province of China, we observed that media impact switched off almost as the epidemic peaked. Our analysis implies that media coverage significantly delayed the epidemic's peak and decreased the severity of the outbreak. Moreover, media impacts are not always effective in lowering the disease transmission during the entire outbreak, but switch on and off in a highly nonlinear fashion with the greatest effect during the early stage of the outbreak. The finding draws the attention to the important role of informing the public about ‘the rate of change of case numbers' rather than ‘the absolute number of cases' to alter behavioral changes, through a self-adaptive media impact switching on and off, for better control of disease transmission.",2015 Jan 16,"['Xiao, Yanni', 'Tang, Sanyi', 'Wu, Jianhong']",Sci Rep,,,True
ce630ae4af71727f479332984f4a1bfbf8ccf670,PMC,Media impact switching surface during an infectious disease outbreak,http://dx.doi.org/10.1038/srep07838,PMC4296304,25592757,CC BY-NC-ND,"There are many challenges to quantifying and evaluating the media impact on the control of emerging infectious diseases. We modeled such media impacts using a piecewise smooth function depending on both the case number and its rate of change. The proposed model was then converted into a switching system, with the switching surface determined by a functional relationship between susceptible populations and different subgroups of infectives. By parameterizing the proposed model with the 2009 A/H1N1 influenza outbreak data in the Shaanxi province of China, we observed that media impact switched off almost as the epidemic peaked. Our analysis implies that media coverage significantly delayed the epidemic's peak and decreased the severity of the outbreak. Moreover, media impacts are not always effective in lowering the disease transmission during the entire outbreak, but switch on and off in a highly nonlinear fashion with the greatest effect during the early stage of the outbreak. The finding draws the attention to the important role of informing the public about ‘the rate of change of case numbers' rather than ‘the absolute number of cases' to alter behavioral changes, through a self-adaptive media impact switching on and off, for better control of disease transmission.",2015 Jan 16,"['Xiao, Yanni', 'Tang, Sanyi', 'Wu, Jianhong']",Sci Rep,,,False
384c7676eb08fb530ec399208932513c0fa0c4e3,PMC,Epidemiological and clinical evaluation of children with respiratory virus infections,,PMC4301222,25664303,CC BY-NC,"Background: Respiratory viruses are the leading cause of respiratory tract infections among children and are responsible for causing morbidity and mortality worldwide. This study was performed to detect viruses in children with respiratory infections and describe their epidemiology and clinical characteristics. Methods: In this descriptive cross sectional study, throat swabs and wash specimens from 202 children younger than six years of age with diagnosis of a respiratory tract infection from a total of 897 specimens were evaluated using multiplex PCR method. Results: Respiratory viruses were detected in 92 children: respiratory synsytial virus, 16.8%; influenza virus, 5.4%; parainfluenza virus, 8.4%; adenovirus, 14.4% and human metapneumo virus 0.49% with male predominance and higher distribution in children younger than 1 year of age with preference in the cold months of year. The clinical presentations of all detected viruses were almost similar. Conclusion: In the present study, nine different respiratory viruses were detected. RSV causes the great majority of respiratory virus infections in children. There was no significant difference in epidemiologic patterns of these viruses in comparison to other studies.",2014 Sep 22,"['Shatizadeh, Somayeh', 'Yavarian, Jila', 'Rezaie, Farhad', 'Mahmoodi, Mahmood', 'Naseri, Maryam', 'Mokhtari Azad, Talat']",Med J Islam Repub Iran,,,True
be179ef4eaf04a9b155ac385eeabc06620a791b2,PMC,Polyionic vaccine adjuvants: another look at aluminum salts and polyelectrolytes,http://dx.doi.org/10.7774/cevr.2015.4.1.23,PMC4313107,25648619,CC BY-NC,"Adjuvants improve the adaptive immune response to a vaccine antigen by modulating innate immunity or facilitating transport and presentation. The selection of an appropriate adjuvant has become vital as new vaccines trend toward narrower composition, expanded application, and improved safety. Functionally, adjuvants act directly or indirectly on antigen presenting cells (APCs) including dendritic cells (DCs) and are perceived as having molecular patterns associated either with pathogen invasion or endogenous cell damage (known as pathogen associated molecular patterns [PAMPs] and damage associated molecular patterns [DAMPs]), thereby initiating sensing and response pathways. PAMP-type adjuvants are ligands for toll-like receptors (TLRs) and can directly affect DCs to alter the strength, potency, speed, duration, bias, breadth, and scope of adaptive immunity. DAMP-type adjuvants signal via proinflammatory pathways and promote immune cell infiltration, antigen presentation, and effector cell maturation. This class of adjuvants includes mineral salts, oil emulsions, nanoparticles, and polyelectrolytes and comprises colloids and molecular assemblies exhibiting complex, heterogeneous structures. Today innovation in adjuvant technology is driven by rapidly expanding knowledge in immunology, cross-fertilization from other areas including systems biology and materials sciences, and regulatory requirements for quality, safety, efficacy and understanding as part of the vaccine product. Standardizations will aid efforts to better define and compare the structure, function and safety of adjuvants. This article briefly surveys the genesis of adjuvant technology and then re-examines polyionic macromolecules and polyelectrolyte materials, adjuvants currently not known to employ TLR. Specific updates are provided for aluminum-based formulations and polyelectrolytes as examples of improvements to the oldest and emerging classes of vaccine adjuvants in use.",2015 Jan 30,"['Powell, Bradford S.', 'Andrianov, Alexander K.', 'Fusco, Peter C.']",Clin Exp Vaccine Res,,,True
9d36c9a5c87380ec6bb1cee77ced91fd6265d343,PMC,Clinical vaccine development,http://dx.doi.org/10.7774/cevr.2015.4.1.46,PMC4313108,25648742,CC BY-NC,"Vaccination is regarded as one of the biggest triumphs in the history of medicine. We are living in the most successful period of vaccine development. The accumulation of multidisciplinary knowledge and the investment of massive funding have enabled the development of vaccines against many infectious diseases as well as other diseases including malignant tumors. The paradigm of clinical vaccine evaluation and licensure has also been modernized based on scientific improvements and historical experience. However, there remain a number of hurdles to overcome. Continuous efforts are focused on increasing the efficacy and reducing the risks related to vaccine use. Cutting-edge knowledge about immunology and microbiology is being rapidly translated to vaccine development. Thus, physicians and others involved in the clinical development of vaccines should have sufficient understanding of the recent developmental trends in vaccination and the diseases of interest.",2015 Jan 30,"Han, Seunghoon",Clin Exp Vaccine Res,,,True
bdb0493b6378d05d55db093b3b6ed45cd68d8a37,PMC,Is the Debate and “Pause” on Experiments That Alter Pathogens with Pandemic Potential Influencing Future Plans of Graduate Students and Postdoctoral Fellows?,http://dx.doi.org/10.1128/mBio.02525-14,PMC4313916,25604793,CC BY-NC-SA,,2015 Jan 20,"Pfeiffer, Julie K.",mBio,,,True
0d0af538cf60b6330d1eb7f5da52bef9ea30fd9c,PMC,Reply to “Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited”,http://dx.doi.org/10.1128/mBio.00041-15,PMC4323416,25616376,CC BY-NC-SA,,2015 Jan 23,"['Lipsitch, Marc', 'Inglesby, Thomas V.']",mBio,,,True
058b7249ce7acc1c14c989cb2d8db27435f81363,PMC,Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited,http://dx.doi.org/10.1128/mBio.02560-14,PMC4323420,25616377,CC BY-NC-SA,,2015 Jan 23,"Fouchier, Ron A. M.",mBio,,,True
e100d3d45507da10018bc2b410c93072756fef47,PMC,"Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the Mycobacterium Neighborhood",http://dx.doi.org/10.1128/mBio.02145-14,PMC4324244,25467442,CC BY-NC-SA,"Newly emerging human viruses such as Ebola virus, severe acute respiratory syndrome (SARS) virus, and HIV likely originate within an extant population of viruses in nonhuman hosts and acquire the ability to infect and cause disease in humans. Although several mechanisms preventing viral infection of particular hosts have been described, the mechanisms and constraints on viral host expansion are ill defined. We describe here mycobacteriophage Patience, a newly isolated phage recovered using Mycobacterium smegmatis mc(2)155 as a host. Patience has genomic features distinct from its M. smegmatis host, including a much lower GC content (50.3% versus 67.4%) and an abundance of codons that are rarely used in M. smegmatis. Nonetheless, it propagates well in M. smegmatis, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. We propose that Patience evolved primarily among lower-GC hosts and that the disparities between its genomic profile and that of M. smegmatis presented only a minimal barrier to host expansion. Rapid adaptions to its new host include recent acquisition of higher-GC genes, expression of out-of-frame proteins within predicted genes, and codon selection among highly expressed genes toward the translational apparatus of its new host.",2014 Dec 2,"['Pope, Welkin H.', 'Jacobs-Sera, Deborah', 'Russell, Daniel A.', 'Rubin, Daniel H. F.', 'Kajee, Afsana', 'Msibi, Zama N. P.', 'Larsen, Michelle H.', 'Jacobs, William R.', 'Lawrence, Jeffrey G.', 'Hendrix, Roger W.', 'Hatfull, Graham F.']",mBio,,,True
703d5a0cdde42cd135397c44a1a235be5b155065,PMC,"Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the Mycobacterium Neighborhood",http://dx.doi.org/10.1128/mBio.02145-14,PMC4324244,25467442,CC BY-NC-SA,"Newly emerging human viruses such as Ebola virus, severe acute respiratory syndrome (SARS) virus, and HIV likely originate within an extant population of viruses in nonhuman hosts and acquire the ability to infect and cause disease in humans. Although several mechanisms preventing viral infection of particular hosts have been described, the mechanisms and constraints on viral host expansion are ill defined. We describe here mycobacteriophage Patience, a newly isolated phage recovered using Mycobacterium smegmatis mc(2)155 as a host. Patience has genomic features distinct from its M. smegmatis host, including a much lower GC content (50.3% versus 67.4%) and an abundance of codons that are rarely used in M. smegmatis. Nonetheless, it propagates well in M. smegmatis, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. We propose that Patience evolved primarily among lower-GC hosts and that the disparities between its genomic profile and that of M. smegmatis presented only a minimal barrier to host expansion. Rapid adaptions to its new host include recent acquisition of higher-GC genes, expression of out-of-frame proteins within predicted genes, and codon selection among highly expressed genes toward the translational apparatus of its new host.",2014 Dec 2,"['Pope, Welkin H.', 'Jacobs-Sera, Deborah', 'Russell, Daniel A.', 'Rubin, Daniel H. F.', 'Kajee, Afsana', 'Msibi, Zama N. P.', 'Larsen, Michelle H.', 'Jacobs, William R.', 'Lawrence, Jeffrey G.', 'Hendrix, Roger W.', 'Hatfull, Graham F.']",mBio,,,False
733f8e669eeeaacee551167ad7adebab21cc0bb7,PMC,"Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the Mycobacterium Neighborhood",http://dx.doi.org/10.1128/mBio.02145-14,PMC4324244,25467442,CC BY-NC-SA,"Newly emerging human viruses such as Ebola virus, severe acute respiratory syndrome (SARS) virus, and HIV likely originate within an extant population of viruses in nonhuman hosts and acquire the ability to infect and cause disease in humans. Although several mechanisms preventing viral infection of particular hosts have been described, the mechanisms and constraints on viral host expansion are ill defined. We describe here mycobacteriophage Patience, a newly isolated phage recovered using Mycobacterium smegmatis mc(2)155 as a host. Patience has genomic features distinct from its M. smegmatis host, including a much lower GC content (50.3% versus 67.4%) and an abundance of codons that are rarely used in M. smegmatis. Nonetheless, it propagates well in M. smegmatis, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. We propose that Patience evolved primarily among lower-GC hosts and that the disparities between its genomic profile and that of M. smegmatis presented only a minimal barrier to host expansion. Rapid adaptions to its new host include recent acquisition of higher-GC genes, expression of out-of-frame proteins within predicted genes, and codon selection among highly expressed genes toward the translational apparatus of its new host.",2014 Dec 2,"['Pope, Welkin H.', 'Jacobs-Sera, Deborah', 'Russell, Daniel A.', 'Rubin, Daniel H. F.', 'Kajee, Afsana', 'Msibi, Zama N. P.', 'Larsen, Michelle H.', 'Jacobs, William R.', 'Lawrence, Jeffrey G.', 'Hendrix, Roger W.', 'Hatfull, Graham F.']",mBio,,,False
94ff46d8e1d56b85d1af8a86ccfe87a8bec6433f,PMC,"Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the Mycobacterium Neighborhood",http://dx.doi.org/10.1128/mBio.02145-14,PMC4324244,25467442,CC BY-NC-SA,"Newly emerging human viruses such as Ebola virus, severe acute respiratory syndrome (SARS) virus, and HIV likely originate within an extant population of viruses in nonhuman hosts and acquire the ability to infect and cause disease in humans. Although several mechanisms preventing viral infection of particular hosts have been described, the mechanisms and constraints on viral host expansion are ill defined. We describe here mycobacteriophage Patience, a newly isolated phage recovered using Mycobacterium smegmatis mc(2)155 as a host. Patience has genomic features distinct from its M. smegmatis host, including a much lower GC content (50.3% versus 67.4%) and an abundance of codons that are rarely used in M. smegmatis. Nonetheless, it propagates well in M. smegmatis, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. We propose that Patience evolved primarily among lower-GC hosts and that the disparities between its genomic profile and that of M. smegmatis presented only a minimal barrier to host expansion. Rapid adaptions to its new host include recent acquisition of higher-GC genes, expression of out-of-frame proteins within predicted genes, and codon selection among highly expressed genes toward the translational apparatus of its new host.",2014 Dec 2,"['Pope, Welkin H.', 'Jacobs-Sera, Deborah', 'Russell, Daniel A.', 'Rubin, Daniel H. F.', 'Kajee, Afsana', 'Msibi, Zama N. P.', 'Larsen, Michelle H.', 'Jacobs, William R.', 'Lawrence, Jeffrey G.', 'Hendrix, Roger W.', 'Hatfull, Graham F.']",mBio,,,False
297243c46102df6e26be232c34fc651fb31589b0,PMC,"Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the Mycobacterium Neighborhood",http://dx.doi.org/10.1128/mBio.02145-14,PMC4324244,25467442,CC BY-NC-SA,"Newly emerging human viruses such as Ebola virus, severe acute respiratory syndrome (SARS) virus, and HIV likely originate within an extant population of viruses in nonhuman hosts and acquire the ability to infect and cause disease in humans. Although several mechanisms preventing viral infection of particular hosts have been described, the mechanisms and constraints on viral host expansion are ill defined. We describe here mycobacteriophage Patience, a newly isolated phage recovered using Mycobacterium smegmatis mc(2)155 as a host. Patience has genomic features distinct from its M. smegmatis host, including a much lower GC content (50.3% versus 67.4%) and an abundance of codons that are rarely used in M. smegmatis. Nonetheless, it propagates well in M. smegmatis, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. We propose that Patience evolved primarily among lower-GC hosts and that the disparities between its genomic profile and that of M. smegmatis presented only a minimal barrier to host expansion. Rapid adaptions to its new host include recent acquisition of higher-GC genes, expression of out-of-frame proteins within predicted genes, and codon selection among highly expressed genes toward the translational apparatus of its new host.",2014 Dec 2,"['Pope, Welkin H.', 'Jacobs-Sera, Deborah', 'Russell, Daniel A.', 'Rubin, Daniel H. F.', 'Kajee, Afsana', 'Msibi, Zama N. P.', 'Larsen, Michelle H.', 'Jacobs, William R.', 'Lawrence, Jeffrey G.', 'Hendrix, Roger W.', 'Hatfull, Graham F.']",mBio,,,False
1a11258656928bd37fcc248819c3fd2e618876c1,PMC,"Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the Mycobacterium Neighborhood",http://dx.doi.org/10.1128/mBio.02145-14,PMC4324244,25467442,CC BY-NC-SA,"Newly emerging human viruses such as Ebola virus, severe acute respiratory syndrome (SARS) virus, and HIV likely originate within an extant population of viruses in nonhuman hosts and acquire the ability to infect and cause disease in humans. Although several mechanisms preventing viral infection of particular hosts have been described, the mechanisms and constraints on viral host expansion are ill defined. We describe here mycobacteriophage Patience, a newly isolated phage recovered using Mycobacterium smegmatis mc(2)155 as a host. Patience has genomic features distinct from its M. smegmatis host, including a much lower GC content (50.3% versus 67.4%) and an abundance of codons that are rarely used in M. smegmatis. Nonetheless, it propagates well in M. smegmatis, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. We propose that Patience evolved primarily among lower-GC hosts and that the disparities between its genomic profile and that of M. smegmatis presented only a minimal barrier to host expansion. Rapid adaptions to its new host include recent acquisition of higher-GC genes, expression of out-of-frame proteins within predicted genes, and codon selection among highly expressed genes toward the translational apparatus of its new host.",2014 Dec 2,"['Pope, Welkin H.', 'Jacobs-Sera, Deborah', 'Russell, Daniel A.', 'Rubin, Daniel H. F.', 'Kajee, Afsana', 'Msibi, Zama N. P.', 'Larsen, Michelle H.', 'Jacobs, William R.', 'Lawrence, Jeffrey G.', 'Hendrix, Roger W.', 'Hatfull, Graham F.']",mBio,,,False
e380b24684c5d2fa7eecf3508456977a6208445a,PMC,"Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the Mycobacterium Neighborhood",http://dx.doi.org/10.1128/mBio.02145-14,PMC4324244,25467442,CC BY-NC-SA,"Newly emerging human viruses such as Ebola virus, severe acute respiratory syndrome (SARS) virus, and HIV likely originate within an extant population of viruses in nonhuman hosts and acquire the ability to infect and cause disease in humans. Although several mechanisms preventing viral infection of particular hosts have been described, the mechanisms and constraints on viral host expansion are ill defined. We describe here mycobacteriophage Patience, a newly isolated phage recovered using Mycobacterium smegmatis mc(2)155 as a host. Patience has genomic features distinct from its M. smegmatis host, including a much lower GC content (50.3% versus 67.4%) and an abundance of codons that are rarely used in M. smegmatis. Nonetheless, it propagates well in M. smegmatis, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. We propose that Patience evolved primarily among lower-GC hosts and that the disparities between its genomic profile and that of M. smegmatis presented only a minimal barrier to host expansion. Rapid adaptions to its new host include recent acquisition of higher-GC genes, expression of out-of-frame proteins within predicted genes, and codon selection among highly expressed genes toward the translational apparatus of its new host.",2014 Dec 2,"['Pope, Welkin H.', 'Jacobs-Sera, Deborah', 'Russell, Daniel A.', 'Rubin, Daniel H. F.', 'Kajee, Afsana', 'Msibi, Zama N. P.', 'Larsen, Michelle H.', 'Jacobs, William R.', 'Lawrence, Jeffrey G.', 'Hendrix, Roger W.', 'Hatfull, Graham F.']",mBio,,,False
5a4293648829bb0d1b27e51e3dd93e8c57ce9a68,PMC,"Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the Mycobacterium Neighborhood",http://dx.doi.org/10.1128/mBio.02145-14,PMC4324244,25467442,CC BY-NC-SA,"Newly emerging human viruses such as Ebola virus, severe acute respiratory syndrome (SARS) virus, and HIV likely originate within an extant population of viruses in nonhuman hosts and acquire the ability to infect and cause disease in humans. Although several mechanisms preventing viral infection of particular hosts have been described, the mechanisms and constraints on viral host expansion are ill defined. We describe here mycobacteriophage Patience, a newly isolated phage recovered using Mycobacterium smegmatis mc(2)155 as a host. Patience has genomic features distinct from its M. smegmatis host, including a much lower GC content (50.3% versus 67.4%) and an abundance of codons that are rarely used in M. smegmatis. Nonetheless, it propagates well in M. smegmatis, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. We propose that Patience evolved primarily among lower-GC hosts and that the disparities between its genomic profile and that of M. smegmatis presented only a minimal barrier to host expansion. Rapid adaptions to its new host include recent acquisition of higher-GC genes, expression of out-of-frame proteins within predicted genes, and codon selection among highly expressed genes toward the translational apparatus of its new host.",2014 Dec 2,"['Pope, Welkin H.', 'Jacobs-Sera, Deborah', 'Russell, Daniel A.', 'Rubin, Daniel H. F.', 'Kajee, Afsana', 'Msibi, Zama N. P.', 'Larsen, Michelle H.', 'Jacobs, William R.', 'Lawrence, Jeffrey G.', 'Hendrix, Roger W.', 'Hatfull, Graham F.']",mBio,,,False
e86d56731c516d072ff226b302dc01d935098bbe,PMC,"Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the Mycobacterium Neighborhood",http://dx.doi.org/10.1128/mBio.02145-14,PMC4324244,25467442,CC BY-NC-SA,"Newly emerging human viruses such as Ebola virus, severe acute respiratory syndrome (SARS) virus, and HIV likely originate within an extant population of viruses in nonhuman hosts and acquire the ability to infect and cause disease in humans. Although several mechanisms preventing viral infection of particular hosts have been described, the mechanisms and constraints on viral host expansion are ill defined. We describe here mycobacteriophage Patience, a newly isolated phage recovered using Mycobacterium smegmatis mc(2)155 as a host. Patience has genomic features distinct from its M. smegmatis host, including a much lower GC content (50.3% versus 67.4%) and an abundance of codons that are rarely used in M. smegmatis. Nonetheless, it propagates well in M. smegmatis, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. We propose that Patience evolved primarily among lower-GC hosts and that the disparities between its genomic profile and that of M. smegmatis presented only a minimal barrier to host expansion. Rapid adaptions to its new host include recent acquisition of higher-GC genes, expression of out-of-frame proteins within predicted genes, and codon selection among highly expressed genes toward the translational apparatus of its new host.",2014 Dec 2,"['Pope, Welkin H.', 'Jacobs-Sera, Deborah', 'Russell, Daniel A.', 'Rubin, Daniel H. F.', 'Kajee, Afsana', 'Msibi, Zama N. P.', 'Larsen, Michelle H.', 'Jacobs, William R.', 'Lawrence, Jeffrey G.', 'Hendrix, Roger W.', 'Hatfull, Graham F.']",mBio,,,False
95742e15e5dc39ed30e4b72398dd4a49507dcec1,PMC,Message in a bottle: lessons learned from antagonism of STING signalling during RNA virus infection,http://dx.doi.org/10.1016/j.cytogfr.2014.08.004,PMC4330990,25212897,CC BY-NC-SA,"STING has emerged in recent years as an important signalling adaptor in the activation of type I interferon responses during infection with DNA viruses and bacteria. An increasing body of evidence suggests that STING also modulates responses to RNA viruses, though the mechanisms remain less clear. In this review, we give a brief overview of the ways in which STING facilitates sensing of RNA viruses. These include modulation of RIG-I-dependent responses through STING's interaction with MAVS, and more speculative mechanisms involving the DNA sensor cGAS and sensing of membrane remodelling events. We then provide an in-depth literature review to summarise the known mechanisms by which RNA viruses of the families Flaviviridae and Coronaviridae evade sensing through STING. Our own work has shown that the NS2B/3 protease complex of the flavivirus dengue virus binds and cleaves STING, and that an inability to degrade murine STING may contribute to host restriction in this virus. We contrast this to the mechanism employed by the distantly related hepacivirus hepatitis C virus, in which STING is bound and inactivated by the NS4B protein. Finally, we discuss STING antagonism in the coronaviruses SARS coronavirus and human coronavirus NL63, which disrupt K63-linked polyubiquitination and dimerisation of STING (both of which are required for STING-mediated activation of IRF-3) via their papain-like proteases. We draw parallels with less-well characterised mechanisms of STING antagonism in related viruses, and place our current knowledge in the context of species tropism restrictions that potentially affect the emergence of new human pathogens.",2014 Dec,"['Maringer, Kevin', 'Fernandez-Sesma, Ana']",Cytokine Growth Factor Rev,,,False
4d9b7d6b31a252255d427fd463344c162ae7c690,PMC,Occupational Hazards in Nursing,,PMC4332998,25699286,CC BY-NC,,2014 Sep 20,"Masoudi Alavi, Negin",Nurs Midwifery Stud,,,True
ca70e687fe7d0471c95bc8e75b588860343fb0c6,PMC,"Unrealistic Optimism, Sex, and Risk Perception of Type 2 Diabetes Onset: Implications for Education Programs",http://dx.doi.org/10.2337/diaspect.28.1.5,PMC4334082,25717271,CC BY-NC-ND,"This study examined links among unrealistic optimism, sex, and risk perception of type 2 diabetes onset in college students. Participants included 660 college students who consented to complete a questionnaire. The results showed significant differences between students who perceived that they were at risk for type 2 diabetes onset and those who thought their peers were the ones at risk. A higher prevalence of participants thought their peers were the ones at risk for type 2 diabetes. Women were more likely than men to report a higher risk perception, indicating that their peers were at lower risk for diabetes onset.",2015 Jan,"['Reyes-Velázquez, Wanda', 'Sealey-Potts, Claudia']",Diabetes Spectr,,,True
2f45403508d925c6fd337bd53f0842e1340a6fcd,PMC,Comparable mRNA expression of inflammatory markers but lower claudin-1 mRNA levels in foreskin tissue of HSV-2 seropositive versus seronegative asymptomatic Kenyan young men,http://dx.doi.org/10.1136/bmjopen-2014-006627,PMC4336463,25694458,CC BY-NC,"OBJECTIVES: Skin biopsies from local sites of herpes simplex virus 2 (HSV-2)-induced ulcers can show infiltrates of inflammatory cells several months after macroscopic healing. We hypothesise that foreskin tissue samples of asymptomatic HSV-2 seropositive men had remaining signs of inflammation at the molecular level. Even in the absence of clinical lesions, genital inflammation may contribute to increased HIV susceptibility on sexual exposure to the virus. SETTING: Foreskin tissue samples were collected from men undergoing elective circumcision in Kisumu, Kenya. PARTICIPANTS: The foreskin tissue samples (n=86) were stratified into study groups based on HSV-2 serology and assessed for mRNA expression of inflammatory markers. Markers of interest were further assessed by immunohistochemical staining within the tissue samples. RESULTS: The two study groups had comparable levels of all molecular markers (CD3, CD4, CD8, CD69, CCR5, HLA-DR, Langerin, DC-SIGN, Mannose Receptor 1, IL-1, IL-6, TNF-α, β7, IgA, IFN-α, CCL5, E-cadherin, ZO-1 and occludin), except for lower mRNA levels of the epithelial junction protein claudin-1 in the HSV-2 seropositive group (p=0.008). Although mRNA levels of claudin-1 were lower in HSV-2 seropositive individuals, the corresponding protein could be visualised in the foreskin epithelium of all samples tested. CONCLUSIONS: Whereas no general inflammation was demonstrated in the foreskin of asymptomatic HSV-2 seropositive individuals, a decreased expression of claudin-1 indicates a less robust genital epithelial barrier. An intact epithelial barrier is essential for blocking mucosal entry of genital infections, including HIV.",2015 Feb 18,"['Röhl, Maria', 'Tjernlund, Annelie', 'Mehta, Supriya D', 'Pettersson, Pernilla', 'Bailey, Robert C', 'Broliden, Kristina']",BMJ Open,,,True
4c565559fff97813a77571986c4c0b34fa3f4d46,PMC,Bioengineering and semisynthesis of an optimized cyclophilin inhibitor for treatment of chronic viral infection,http://dx.doi.org/10.1016/j.chembiol.2014.10.023,PMC4336584,25619934,CC BY-NC,"Inhibition of host-encoded targets, such as the cyclophilins, provides an opportunity to generate potent, high barrier to resistance antivirals for the treatment of a broad range of viral diseases. However, many host-targeted agents are natural products which can be difficult to optimize using synthetic chemistry alone. We describe the orthogonal combination of bioengineering and semisynthetic chemistry to optimize the drug-like properties of sanglifehrin A, a known cyclophilin inhibitor of mixed non-ribosomal peptide/polyketide origin in order to generate the drug candidate NVP018 (formerly BC556). NVP018 is a potent inhibitor of HBV, HCV and HIV-1 replication, shows minimal inhibition of major drug transporters and has a high barrier to generation of both HCV and HIV-1 resistance.",2015 Feb 19,"['Hansson, Magnus Joakim', 'Moss, Steven James', 'Bobardt, Michael', 'Chatterji, Udayan', 'Coates, Nigel', 'Garcia-Rivera, Jose A', 'Elmér, Eskil', 'Kendrew, Steve', 'Leyssen, Pieter', 'Neyts, Johan', 'Nur-E-Alam, Mohammad', 'Warneck, Tony', 'Wilkinson, Barrie', 'Gallay, Philippe', 'Gregory, Matthew Alan']",Chem Biol,,,True
1da4278cead869b78e5bf6205013a8407944f1f6,PMC,Bioengineering and semisynthesis of an optimized cyclophilin inhibitor for treatment of chronic viral infection,http://dx.doi.org/10.1016/j.chembiol.2014.10.023,PMC4336584,25619934,CC BY-NC,"Inhibition of host-encoded targets, such as the cyclophilins, provides an opportunity to generate potent, high barrier to resistance antivirals for the treatment of a broad range of viral diseases. However, many host-targeted agents are natural products which can be difficult to optimize using synthetic chemistry alone. We describe the orthogonal combination of bioengineering and semisynthetic chemistry to optimize the drug-like properties of sanglifehrin A, a known cyclophilin inhibitor of mixed non-ribosomal peptide/polyketide origin in order to generate the drug candidate NVP018 (formerly BC556). NVP018 is a potent inhibitor of HBV, HCV and HIV-1 replication, shows minimal inhibition of major drug transporters and has a high barrier to generation of both HCV and HIV-1 resistance.",2015 Feb 19,"['Hansson, Magnus Joakim', 'Moss, Steven James', 'Bobardt, Michael', 'Chatterji, Udayan', 'Coates, Nigel', 'Garcia-Rivera, Jose A', 'Elmér, Eskil', 'Kendrew, Steve', 'Leyssen, Pieter', 'Neyts, Johan', 'Nur-E-Alam, Mohammad', 'Warneck, Tony', 'Wilkinson, Barrie', 'Gallay, Philippe', 'Gregory, Matthew Alan']",Chem Biol,,,True
c57c03bb0a34cfdb6d05fce8c1502707de2e9175,PMC,Bioengineering and semisynthesis of an optimized cyclophilin inhibitor for treatment of chronic viral infection,http://dx.doi.org/10.1016/j.chembiol.2014.10.023,PMC4336584,25619934,CC BY-NC,"Inhibition of host-encoded targets, such as the cyclophilins, provides an opportunity to generate potent, high barrier to resistance antivirals for the treatment of a broad range of viral diseases. However, many host-targeted agents are natural products which can be difficult to optimize using synthetic chemistry alone. We describe the orthogonal combination of bioengineering and semisynthetic chemistry to optimize the drug-like properties of sanglifehrin A, a known cyclophilin inhibitor of mixed non-ribosomal peptide/polyketide origin in order to generate the drug candidate NVP018 (formerly BC556). NVP018 is a potent inhibitor of HBV, HCV and HIV-1 replication, shows minimal inhibition of major drug transporters and has a high barrier to generation of both HCV and HIV-1 resistance.",2015 Feb 19,"['Hansson, Magnus Joakim', 'Moss, Steven James', 'Bobardt, Michael', 'Chatterji, Udayan', 'Coates, Nigel', 'Garcia-Rivera, Jose A', 'Elmér, Eskil', 'Kendrew, Steve', 'Leyssen, Pieter', 'Neyts, Johan', 'Nur-E-Alam, Mohammad', 'Warneck, Tony', 'Wilkinson, Barrie', 'Gallay, Philippe', 'Gregory, Matthew Alan']",Chem Biol,,,True
a5fddb00475627b88f2761218d9e6a572d14f90d,PMC,Systems-Based Analysis of the Sarcocystis neurona Genome Identifies Pathways That Contribute to a Heteroxenous Life Cycle,http://dx.doi.org/10.1128/mBio.02445-14,PMC4337577,25670772,CC BY-NC-SA,"Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The S. neurona genome is 127 Mbp, more than twice the size of other sequenced coccidian genomes. Comparative analyses identified conservation of the invasion machinery among the coccidia. However, many dense-granule and rhoptry kinase genes, responsible for altering host effector pathways in Toxoplasma and Neospora, are absent from S. neurona. Further, S. neurona has a divergent repertoire of SRS proteins, previously implicated in tissue cyst formation in Toxoplasma. Systems-based analyses identified a series of metabolic innovations, including the ability to exploit alternative sources of energy. Finally, we present an S. neurona model detailing conserved molecular innovations that promote the transition from a purely enteric lifestyle (Eimeria) to a heteroxenous parasite capable of infecting a wide range of intermediate hosts.",2015 Feb 10,"['Blazejewski, Tomasz', 'Nursimulu, Nirvana', 'Pszenny, Viviana', 'Dangoudoubiyam, Sriveny', 'Namasivayam, Sivaranjani', 'Chiasson, Melissa A.', 'Chessman, Kyle', 'Tonkin, Michelle', 'Swapna, Lakshmipuram S.', 'Hung, Stacy S.', 'Bridgers, Joshua', 'Ricklefs, Stacy M.', 'Boulanger, Martin J.', 'Dubey, Jitender P.', 'Porcella, Stephen F.', 'Kissinger, Jessica C.', 'Howe, Daniel K.', 'Grigg, Michael E.', 'Parkinson, John']",mBio,,,True
25ce5d9714e91f9a42b309af510327c9a56536a0,PMC,Systems-Based Analysis of the Sarcocystis neurona Genome Identifies Pathways That Contribute to a Heteroxenous Life Cycle,http://dx.doi.org/10.1128/mBio.02445-14,PMC4337577,25670772,CC BY-NC-SA,"Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The S. neurona genome is 127 Mbp, more than twice the size of other sequenced coccidian genomes. Comparative analyses identified conservation of the invasion machinery among the coccidia. However, many dense-granule and rhoptry kinase genes, responsible for altering host effector pathways in Toxoplasma and Neospora, are absent from S. neurona. Further, S. neurona has a divergent repertoire of SRS proteins, previously implicated in tissue cyst formation in Toxoplasma. Systems-based analyses identified a series of metabolic innovations, including the ability to exploit alternative sources of energy. Finally, we present an S. neurona model detailing conserved molecular innovations that promote the transition from a purely enteric lifestyle (Eimeria) to a heteroxenous parasite capable of infecting a wide range of intermediate hosts.",2015 Feb 10,"['Blazejewski, Tomasz', 'Nursimulu, Nirvana', 'Pszenny, Viviana', 'Dangoudoubiyam, Sriveny', 'Namasivayam, Sivaranjani', 'Chiasson, Melissa A.', 'Chessman, Kyle', 'Tonkin, Michelle', 'Swapna, Lakshmipuram S.', 'Hung, Stacy S.', 'Bridgers, Joshua', 'Ricklefs, Stacy M.', 'Boulanger, Martin J.', 'Dubey, Jitender P.', 'Porcella, Stephen F.', 'Kissinger, Jessica C.', 'Howe, Daniel K.', 'Grigg, Michael E.', 'Parkinson, John']",mBio,,,False
b54c80297872e9ea4036868879e47e9e6cd7e79c,PMC,Systems-Based Analysis of the Sarcocystis neurona Genome Identifies Pathways That Contribute to a Heteroxenous Life Cycle,http://dx.doi.org/10.1128/mBio.02445-14,PMC4337577,25670772,CC BY-NC-SA,"Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The S. neurona genome is 127 Mbp, more than twice the size of other sequenced coccidian genomes. Comparative analyses identified conservation of the invasion machinery among the coccidia. However, many dense-granule and rhoptry kinase genes, responsible for altering host effector pathways in Toxoplasma and Neospora, are absent from S. neurona. Further, S. neurona has a divergent repertoire of SRS proteins, previously implicated in tissue cyst formation in Toxoplasma. Systems-based analyses identified a series of metabolic innovations, including the ability to exploit alternative sources of energy. Finally, we present an S. neurona model detailing conserved molecular innovations that promote the transition from a purely enteric lifestyle (Eimeria) to a heteroxenous parasite capable of infecting a wide range of intermediate hosts.",2015 Feb 10,"['Blazejewski, Tomasz', 'Nursimulu, Nirvana', 'Pszenny, Viviana', 'Dangoudoubiyam, Sriveny', 'Namasivayam, Sivaranjani', 'Chiasson, Melissa A.', 'Chessman, Kyle', 'Tonkin, Michelle', 'Swapna, Lakshmipuram S.', 'Hung, Stacy S.', 'Bridgers, Joshua', 'Ricklefs, Stacy M.', 'Boulanger, Martin J.', 'Dubey, Jitender P.', 'Porcella, Stephen F.', 'Kissinger, Jessica C.', 'Howe, Daniel K.', 'Grigg, Michael E.', 'Parkinson, John']",mBio,,,False
1cb4c38835fd77d70bb88c6d14821fedbfa594dd,PMC,Systems-Based Analysis of the Sarcocystis neurona Genome Identifies Pathways That Contribute to a Heteroxenous Life Cycle,http://dx.doi.org/10.1128/mBio.02445-14,PMC4337577,25670772,CC BY-NC-SA,"Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The S. neurona genome is 127 Mbp, more than twice the size of other sequenced coccidian genomes. Comparative analyses identified conservation of the invasion machinery among the coccidia. However, many dense-granule and rhoptry kinase genes, responsible for altering host effector pathways in Toxoplasma and Neospora, are absent from S. neurona. Further, S. neurona has a divergent repertoire of SRS proteins, previously implicated in tissue cyst formation in Toxoplasma. Systems-based analyses identified a series of metabolic innovations, including the ability to exploit alternative sources of energy. Finally, we present an S. neurona model detailing conserved molecular innovations that promote the transition from a purely enteric lifestyle (Eimeria) to a heteroxenous parasite capable of infecting a wide range of intermediate hosts.",2015 Feb 10,"['Blazejewski, Tomasz', 'Nursimulu, Nirvana', 'Pszenny, Viviana', 'Dangoudoubiyam, Sriveny', 'Namasivayam, Sivaranjani', 'Chiasson, Melissa A.', 'Chessman, Kyle', 'Tonkin, Michelle', 'Swapna, Lakshmipuram S.', 'Hung, Stacy S.', 'Bridgers, Joshua', 'Ricklefs, Stacy M.', 'Boulanger, Martin J.', 'Dubey, Jitender P.', 'Porcella, Stephen F.', 'Kissinger, Jessica C.', 'Howe, Daniel K.', 'Grigg, Michael E.', 'Parkinson, John']",mBio,,,False
756750d6c69ed2d75c0ab961644c436a6da13705,PMC,Systems-Based Analysis of the Sarcocystis neurona Genome Identifies Pathways That Contribute to a Heteroxenous Life Cycle,http://dx.doi.org/10.1128/mBio.02445-14,PMC4337577,25670772,CC BY-NC-SA,"Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The S. neurona genome is 127 Mbp, more than twice the size of other sequenced coccidian genomes. Comparative analyses identified conservation of the invasion machinery among the coccidia. However, many dense-granule and rhoptry kinase genes, responsible for altering host effector pathways in Toxoplasma and Neospora, are absent from S. neurona. Further, S. neurona has a divergent repertoire of SRS proteins, previously implicated in tissue cyst formation in Toxoplasma. Systems-based analyses identified a series of metabolic innovations, including the ability to exploit alternative sources of energy. Finally, we present an S. neurona model detailing conserved molecular innovations that promote the transition from a purely enteric lifestyle (Eimeria) to a heteroxenous parasite capable of infecting a wide range of intermediate hosts.",2015 Feb 10,"['Blazejewski, Tomasz', 'Nursimulu, Nirvana', 'Pszenny, Viviana', 'Dangoudoubiyam, Sriveny', 'Namasivayam, Sivaranjani', 'Chiasson, Melissa A.', 'Chessman, Kyle', 'Tonkin, Michelle', 'Swapna, Lakshmipuram S.', 'Hung, Stacy S.', 'Bridgers, Joshua', 'Ricklefs, Stacy M.', 'Boulanger, Martin J.', 'Dubey, Jitender P.', 'Porcella, Stephen F.', 'Kissinger, Jessica C.', 'Howe, Daniel K.', 'Grigg, Michael E.', 'Parkinson, John']",mBio,,,False
26e2bef8d203772525eb7304395d27bb25c7ce51,PMC,Systems-Based Analysis of the Sarcocystis neurona Genome Identifies Pathways That Contribute to a Heteroxenous Life Cycle,http://dx.doi.org/10.1128/mBio.02445-14,PMC4337577,25670772,CC BY-NC-SA,"Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The S. neurona genome is 127 Mbp, more than twice the size of other sequenced coccidian genomes. Comparative analyses identified conservation of the invasion machinery among the coccidia. However, many dense-granule and rhoptry kinase genes, responsible for altering host effector pathways in Toxoplasma and Neospora, are absent from S. neurona. Further, S. neurona has a divergent repertoire of SRS proteins, previously implicated in tissue cyst formation in Toxoplasma. Systems-based analyses identified a series of metabolic innovations, including the ability to exploit alternative sources of energy. Finally, we present an S. neurona model detailing conserved molecular innovations that promote the transition from a purely enteric lifestyle (Eimeria) to a heteroxenous parasite capable of infecting a wide range of intermediate hosts.",2015 Feb 10,"['Blazejewski, Tomasz', 'Nursimulu, Nirvana', 'Pszenny, Viviana', 'Dangoudoubiyam, Sriveny', 'Namasivayam, Sivaranjani', 'Chiasson, Melissa A.', 'Chessman, Kyle', 'Tonkin, Michelle', 'Swapna, Lakshmipuram S.', 'Hung, Stacy S.', 'Bridgers, Joshua', 'Ricklefs, Stacy M.', 'Boulanger, Martin J.', 'Dubey, Jitender P.', 'Porcella, Stephen F.', 'Kissinger, Jessica C.', 'Howe, Daniel K.', 'Grigg, Michael E.', 'Parkinson, John']",mBio,,,False
28d987c4ec40dafc05993e3a209ea4266f270f28,PMC,Systems-Based Analysis of the Sarcocystis neurona Genome Identifies Pathways That Contribute to a Heteroxenous Life Cycle,http://dx.doi.org/10.1128/mBio.02445-14,PMC4337577,25670772,CC BY-NC-SA,"Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The S. neurona genome is 127 Mbp, more than twice the size of other sequenced coccidian genomes. Comparative analyses identified conservation of the invasion machinery among the coccidia. However, many dense-granule and rhoptry kinase genes, responsible for altering host effector pathways in Toxoplasma and Neospora, are absent from S. neurona. Further, S. neurona has a divergent repertoire of SRS proteins, previously implicated in tissue cyst formation in Toxoplasma. Systems-based analyses identified a series of metabolic innovations, including the ability to exploit alternative sources of energy. Finally, we present an S. neurona model detailing conserved molecular innovations that promote the transition from a purely enteric lifestyle (Eimeria) to a heteroxenous parasite capable of infecting a wide range of intermediate hosts.",2015 Feb 10,"['Blazejewski, Tomasz', 'Nursimulu, Nirvana', 'Pszenny, Viviana', 'Dangoudoubiyam, Sriveny', 'Namasivayam, Sivaranjani', 'Chiasson, Melissa A.', 'Chessman, Kyle', 'Tonkin, Michelle', 'Swapna, Lakshmipuram S.', 'Hung, Stacy S.', 'Bridgers, Joshua', 'Ricklefs, Stacy M.', 'Boulanger, Martin J.', 'Dubey, Jitender P.', 'Porcella, Stephen F.', 'Kissinger, Jessica C.', 'Howe, Daniel K.', 'Grigg, Michael E.', 'Parkinson, John']",mBio,,,True
e371217b1bd08c24847841b732b16fabd41d6b12,PMC,Systems-Based Analysis of the Sarcocystis neurona Genome Identifies Pathways That Contribute to a Heteroxenous Life Cycle,http://dx.doi.org/10.1128/mBio.02445-14,PMC4337577,25670772,CC BY-NC-SA,"Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The S. neurona genome is 127 Mbp, more than twice the size of other sequenced coccidian genomes. Comparative analyses identified conservation of the invasion machinery among the coccidia. However, many dense-granule and rhoptry kinase genes, responsible for altering host effector pathways in Toxoplasma and Neospora, are absent from S. neurona. Further, S. neurona has a divergent repertoire of SRS proteins, previously implicated in tissue cyst formation in Toxoplasma. Systems-based analyses identified a series of metabolic innovations, including the ability to exploit alternative sources of energy. Finally, we present an S. neurona model detailing conserved molecular innovations that promote the transition from a purely enteric lifestyle (Eimeria) to a heteroxenous parasite capable of infecting a wide range of intermediate hosts.",2015 Feb 10,"['Blazejewski, Tomasz', 'Nursimulu, Nirvana', 'Pszenny, Viviana', 'Dangoudoubiyam, Sriveny', 'Namasivayam, Sivaranjani', 'Chiasson, Melissa A.', 'Chessman, Kyle', 'Tonkin, Michelle', 'Swapna, Lakshmipuram S.', 'Hung, Stacy S.', 'Bridgers, Joshua', 'Ricklefs, Stacy M.', 'Boulanger, Martin J.', 'Dubey, Jitender P.', 'Porcella, Stephen F.', 'Kissinger, Jessica C.', 'Howe, Daniel K.', 'Grigg, Michael E.', 'Parkinson, John']",mBio,,,False
19ab7ec27d359cd0403b9962e95c206f87351199,PMC,Systems-Based Analysis of the Sarcocystis neurona Genome Identifies Pathways That Contribute to a Heteroxenous Life Cycle,http://dx.doi.org/10.1128/mBio.02445-14,PMC4337577,25670772,CC BY-NC-SA,"Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The S. neurona genome is 127 Mbp, more than twice the size of other sequenced coccidian genomes. Comparative analyses identified conservation of the invasion machinery among the coccidia. However, many dense-granule and rhoptry kinase genes, responsible for altering host effector pathways in Toxoplasma and Neospora, are absent from S. neurona. Further, S. neurona has a divergent repertoire of SRS proteins, previously implicated in tissue cyst formation in Toxoplasma. Systems-based analyses identified a series of metabolic innovations, including the ability to exploit alternative sources of energy. Finally, we present an S. neurona model detailing conserved molecular innovations that promote the transition from a purely enteric lifestyle (Eimeria) to a heteroxenous parasite capable of infecting a wide range of intermediate hosts.",2015 Feb 10,"['Blazejewski, Tomasz', 'Nursimulu, Nirvana', 'Pszenny, Viviana', 'Dangoudoubiyam, Sriveny', 'Namasivayam, Sivaranjani', 'Chiasson, Melissa A.', 'Chessman, Kyle', 'Tonkin, Michelle', 'Swapna, Lakshmipuram S.', 'Hung, Stacy S.', 'Bridgers, Joshua', 'Ricklefs, Stacy M.', 'Boulanger, Martin J.', 'Dubey, Jitender P.', 'Porcella, Stephen F.', 'Kissinger, Jessica C.', 'Howe, Daniel K.', 'Grigg, Michael E.', 'Parkinson, John']",mBio,,,False
3be2b917c48e3dc25a4e6bb3028fd5d32e4f2d9d,PMC,Strategic measures for the control of surging antimicrobial resistance in Hong Kong and mainland of China,http://dx.doi.org/10.1038/emi.2015.8,PMC4345289,26038766,CC BY-NC-ND,"Antimicrobial-resistant bacteria are either highly prevalent or increasing rapidly in Hong Kong and China. Treatment options for these bacteria are generally limited, less effective and more expensive. The emergence and dynamics of antimicrobial resistance genes in bacteria circulating between animals, the environment and humans are not entirely known. Nonetheless, selective pressure by antibiotics on the microbiomes of animal and human, and their associated environments (especially farms and healthcare institutions), sewage systems and soil are likely to confer survival advantages upon bacteria with antimicrobial-resistance genes, which may be further disseminated through plasmids or transposons with integrons. Therefore, antibiotic use must be tightly regulated to eliminate such selective pressure, including the illegalization of antibiotics as growth promoters in animal feed and regulation of antibiotic use in veterinary practice and human medicine. Heightened awareness of infection control measures to reduce the risk of acquiring resistant bacteria is essential, especially during antimicrobial use or institutionalization in healthcare facilities. The transmission cycle must be interrupted by proper hand hygiene, environmental cleaning, avoidance of undercooked or raw food and compliance with infection control measures by healthcare workers, visitors and patients, especially during treatment with antibiotics. In addition to these routine measures, proactive microbiological screening of hospitalized patients with risk factors for carrying resistant bacteria, including history of travel to endemic countries, transfer from other hospitals, and prolonged hospitalization; directly observed hand hygiene before oral intake of drugs, food and drinks; and targeted disinfection of high-touch or mutual-touch items, such as bed rails and bed curtains, are important. Transparency of surveillance data from each institute for public scrutiny provides an incentive for controlling antimicrobial resistance in healthcare settings at an administrative level.",2015 Feb 11,"['Cheng, Vincent CC', 'Wong, Sally CY', 'Ho, Pak-Leung', 'Yuen, Kwok-Yung']",Emerg Microbes Infect,,,True
89f214be6e76049510daa238a9182f8302cfdbbb,PMC,Viral Profile of COPD Exacerbations According to Patients§,http://dx.doi.org/10.2174/1874306401509010001,PMC4347051,25741393,CC BY-NC,"BACKGROUND : To compare the differences between elderly and non-elderly patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) due to viral infections. METHODS : Patients with chronic obstructive pulmonary disease (COPD) exacerbation were recruited and classified as elderly (>65 years) and non-elderly (≤ 65 years). Sputum and oropharyngeal samples were assessed, PCR for respiratory viruses and cultures for common pathogens were performed. RESULTS : 247 patients (median age: 69.3±9.5 years) were recruited and categorized into group A: non-elderly patients [n=81 (32.8%), median age 58±5.99] and group B: elderly patients [n=166 (67.2%), median age 74.8±4.8] years. In 133 (53.8%) patients a viral infection was identified and in 34 (13.8%) a bacterial pathogen was isolated from cultures. In 18 (7.3%) patients a double infection (bacterial+viral) was identified. In group B, the presence of cardiac failure (46.6% vs 28.3%, p<0.001), renal failure (10.5% vs 4%, p=0.03), bacterial co-infection (13.8% vs 7.4%, p=0.04), influenza vaccination rates (45.5% vs 215, p<0.001), and longer hospital stay (8.4±4.4 vs 7.5±3.2 days, p=0.02) were higher than group A. The overall rate of viral infections did not differ according to age. A trend to higher rates of infection with parainfluenza 3 [19 (20%) patients in group B vs3 (7.5%) patients in group A, p=0.04] was observed in older patients. CONCLUSION : No differences on the rate and type of viral infections were noted for elderly vs non elderly patients. However, they tended to have more bacterial co-infections that led to AECOPD and longer hospitalization stays compared to non-elderly patients.",2015 Feb 23,"['Dimopoulos, G', 'Tsiodras, S', 'Lerikou, M', 'Chranioti, Aik', 'Perros, E', 'Anagnostopoulou, U', 'Karakitsos, P', 'Armaganidis, A']",Open Respir Med J,,,True
e494ed8c504a8312c9df7936a8fc832e86d444e6,PMC,"Detection of rickettsial DNA in ticks and wild boars in Kyoto City, Japan",http://dx.doi.org/10.1292/jvms.14-0451,PMC4347921,25298315,CC BY-NC-ND,"The tick is a well-known vector for arthropod-borne pathogens, such as tick-borne encephalitis, Lyme disease, Japanese spotted fever and severe fever with thrombocytopenia syndrome. It is therefore important to know the tick population and distribution in our environment and wild animals in order to prevent tick-borne diseases. Here, we report the results of tick surveillance from May to September 2011 at 14 geographical points and in 5 wild boars in Kyoto City, Kyoto prefecture, Japan. We collected 3,198 ticks comprising 5 tick species, Haemaphysalis (H.) longicornis, H. flava, H. kitaokai, Amblyomma testudinarium and Dermacentor taiwanensis. Interestingly, the proportion of tick species varied according to geographical region within the city. The ticks collected in the city were reported as potential vectors of pathogens, such as rickettsiosis. We detected rickettsial DNA by PCR in 71.1% of 201 ticks investigated. The ticks that carried rickettsiae were distributed across the whole the city. The sequences of PCR-amplified DNA fragments were determined and showed similarities to spotted fever group rickettsiae. Although their pathogenicity for animals including humans is still unclear, it is important to stay alert and pay attention to tick-borne diseases in order to ensure the safety of the citizens of the city as well as that of visitors.",2015 Jan 8,"['SOMEYA, Azusa', 'ITO, Ryuki', 'MAEDA, Akihiko', 'IKENAGA, Mitsuhiro']",J Vet Med Sci,,,True
67c79979c388cfcad87bb12d0ea644699500d736,PMC,"Guidance on the use of antiviral drugs for influenza in acute care facilities in Canada, 2014–2015",,PMC4353274,25798159,CC BY-NC,This article represents the second update to the AMMI Canada Guidelines document on the use of antiviral drugs for influenza. The article aims to inform health care professionals of the increased risk for influenza in long-term care facilities due to a documented mismatch between the components chosen for this season’s vaccine and currently circulating influenza strains. Adjusted recommendations for the use of antiviral drugs for influenza in the acute care setting for this season are provided.,2015 Jan-Feb,"['Stiver, H Grant', 'Evans, Gerald A', 'Aoki, Fred Y', 'Allen, Upton D', 'Laverdière, Michel']",Can J Infect Dis Med Microbiol,,,True
1a7bbed39ffe0668daf962693c7e053d6709d0bb,PMC,Disseminated Conidiobolus incongruus in a dog: A case report and literature review,http://dx.doi.org/10.1016/j.mmcr.2015.02.005,PMC4354915,25830088,CC BY-NC-ND,"Conidiobolomycosis is a rare fungal disease of both humans and animals, occurring mainly in tropical and subtropical climates. We describe a disseminated fungal infection in a young, apparently immunocompetent dog who initially presented for antibiotic resistant pneumonia. Histopathology and mycology identified a Conidiobolus sp., further confirmed as Conidiobolus incongruus through DNA sequencing of D1/D2 regions. This is the first report of this species causing disease in dogs and the fifth reported infection in animals.",2015 Feb 25,"['Mackey, Paige E.', 'Cappe, Katharine G.', 'Mani, Rinosh', 'Rothenburg, Lana', 'Sutton, Deanna A.', 'Wiederhold, Nathan P.', 'Lindner, Jonathan', 'Ramachandran, Akhilesh', 'Wall, Corey R.', 'Snider, Timothy']",Med Mycol Case Rep,,,False
a9a33f1d0a7dee1c6fb63346baa0d6565fc79c00,PMC,Alu RNA regulates the cellular pool of active ribosomes by targeted delivery of SRP9/14 to 40S subunits,http://dx.doi.org/10.1093/nar/gkv048,PMC4357698,25697503,CC BY-NC,"The human genome contains about 1.5 million Alu elements, which are transcribed into Alu RNAs by RNA polymerase III. Their expression is upregulated following stress and viral infection, and they associate with the SRP9/14 protein dimer in the cytoplasm forming Alu RNPs. Using cell-free translation, we have previously shown that Alu RNPs inhibit polysome formation. Here, we describe the mechanism of Alu RNP-mediated inhibition of translation initiation and demonstrate its effect on translation of cellular and viral RNAs. Both cap-dependent and IRES-mediated initiation is inhibited. Inhibition involves direct binding of SRP9/14 to 40S ribosomal subunits and requires Alu RNA as an assembly factor but its continuous association with 40S subunits is not required for inhibition. Binding of SRP9/14 to 40S prevents 48S complex formation by interfering with the recruitment of mRNA to 40S subunits. In cells, overexpression of Alu RNA decreases translation of reporter mRNAs and this effect is alleviated with a mutation that reduces its affinity for SRP9/14. Alu RNPs also inhibit the translation of cellular mRNAs resuming translation after stress and of viral mRNAs suggesting a role of Alu RNPs in adapting the translational output in response to stress and viral infection.",2015 Mar 11,"['Ivanova, Elena', 'Berger, Audrey', 'Scherrer, Anne', 'Alkalaeva, Elena', 'Strub, Katharina']",Nucleic Acids Res,,,True
eb5476698f1fd39bed192f7ec8211953f78537b3,PMC,Alu RNA regulates the cellular pool of active ribosomes by targeted delivery of SRP9/14 to 40S subunits,http://dx.doi.org/10.1093/nar/gkv048,PMC4357698,25697503,CC BY-NC,"The human genome contains about 1.5 million Alu elements, which are transcribed into Alu RNAs by RNA polymerase III. Their expression is upregulated following stress and viral infection, and they associate with the SRP9/14 protein dimer in the cytoplasm forming Alu RNPs. Using cell-free translation, we have previously shown that Alu RNPs inhibit polysome formation. Here, we describe the mechanism of Alu RNP-mediated inhibition of translation initiation and demonstrate its effect on translation of cellular and viral RNAs. Both cap-dependent and IRES-mediated initiation is inhibited. Inhibition involves direct binding of SRP9/14 to 40S ribosomal subunits and requires Alu RNA as an assembly factor but its continuous association with 40S subunits is not required for inhibition. Binding of SRP9/14 to 40S prevents 48S complex formation by interfering with the recruitment of mRNA to 40S subunits. In cells, overexpression of Alu RNA decreases translation of reporter mRNAs and this effect is alleviated with a mutation that reduces its affinity for SRP9/14. Alu RNPs also inhibit the translation of cellular mRNAs resuming translation after stress and of viral mRNAs suggesting a role of Alu RNPs in adapting the translational output in response to stress and viral infection.",2015 Mar 11,"['Ivanova, Elena', 'Berger, Audrey', 'Scherrer, Anne', 'Alkalaeva, Elena', 'Strub, Katharina']",Nucleic Acids Res,,,True
58f660cec9eb4423fc12e1b14bc70a951a5edad0,PMC,Synergistic effects of ATP and RNA binding to human DEAD-box protein DDX1,http://dx.doi.org/10.1093/nar/gkv106,PMC4357711,25690890,CC BY-NC,"RNA helicases of the DEAD-box protein family form the largest group of helicases. The human DEAD-box protein 1 (DDX1) plays an important role in tRNA and mRNA processing, is involved in tumor progression and is also hijacked by several virus families such as HIV-1 for replication and nuclear export. Although important in many cellular processes, the mechanism of DDX1′s enzymatic function is unknown. We have performed equilibrium titrations and transient kinetics to determine affinities for nucleotides and RNA. We find an exceptional tight binding of DDX1 to adenosine diphosphate (ADP), one of the strongest affinities observed for DEAD-box helicases. ADP binds tighter by three orders of magnitude when compared to adenosine triphosphate (ATP), arresting the enzyme in a potential dead-end ADP conformation under physiological conditions. We thus suggest that a nucleotide exchange factor leads to DDX1 recycling. Furthermore, we find a strong cooperativity in binding of RNA and ATP to DDX1 that is also reflected in ATP hydrolysis. We present a model in which either ATP or RNA binding alone can partially shift the equilibrium from an ‘open’ to a ‘closed’-state; this shift appears to be not further pronounced substantially even in the presence of both RNA and ATP as the low rate of ATP hydrolysis does not change.",2015 Mar 11,"['Kellner, Julian N.', 'Reinstein, Jochen', 'Meinhart, Anton']",Nucleic Acids Res,,,True
eb93befc89c6e31c873386d95150e87dfd849e73,PMC,Synergistic effects of ATP and RNA binding to human DEAD-box protein DDX1,http://dx.doi.org/10.1093/nar/gkv106,PMC4357711,25690890,CC BY-NC,"RNA helicases of the DEAD-box protein family form the largest group of helicases. The human DEAD-box protein 1 (DDX1) plays an important role in tRNA and mRNA processing, is involved in tumor progression and is also hijacked by several virus families such as HIV-1 for replication and nuclear export. Although important in many cellular processes, the mechanism of DDX1′s enzymatic function is unknown. We have performed equilibrium titrations and transient kinetics to determine affinities for nucleotides and RNA. We find an exceptional tight binding of DDX1 to adenosine diphosphate (ADP), one of the strongest affinities observed for DEAD-box helicases. ADP binds tighter by three orders of magnitude when compared to adenosine triphosphate (ATP), arresting the enzyme in a potential dead-end ADP conformation under physiological conditions. We thus suggest that a nucleotide exchange factor leads to DDX1 recycling. Furthermore, we find a strong cooperativity in binding of RNA and ATP to DDX1 that is also reflected in ATP hydrolysis. We present a model in which either ATP or RNA binding alone can partially shift the equilibrium from an ‘open’ to a ‘closed’-state; this shift appears to be not further pronounced substantially even in the presence of both RNA and ATP as the low rate of ATP hydrolysis does not change.",2015 Mar 11,"['Kellner, Julian N.', 'Reinstein, Jochen', 'Meinhart, Anton']",Nucleic Acids Res,,,True
7fedd1176b41cfd4cc01538305f91439304abee7,PMC,Structure-based identification of functional residues in the nucleoside-2′-O-methylase domain of Bluetongue virus VP4 capping enzyme,http://dx.doi.org/10.1016/j.fob.2015.02.001,PMC4359970,25834778,CC BY-NC-ND,"Bluetongue virus (BTV) encodes a single capping protein, VP4, which catalyzes all reactions required to generate cap1 structures on nascent viral transcripts. Further, structural analysis by X-ray crystallography indicated each catalytic reaction is arranged as a discrete domain, including a nucleoside-2′-O-methyltransferase (2′-O MTase). In this study, we have exploited the structural information to identify the residues that are important for the catalytic activity of 2′-O MTase of VP4 and their influence on BTV replication. The effect of these mutations on GMP binding, guanylyltransferase (GTase) and methylase activities were analysed by a series of in vitro biochemical assays using recombinant mutant proteins; subsequently their effects on virus replication were assessed by introducing the same mutations in replicating viral genome using a reverse genetics system. Our data showed that single substitution mutations in the catalytic tetrad K-D-K-E were sufficient to abolish 2′-O MTase activity in vitro and to completely abrogate BTV replication in cells; although these mutants retained the upstream GMP binding, GTase and guanine-N7-methyltransferase activities. Mutations of the surrounding substrate-binding pocket (predicted to recruit cap0) had variable effects on in vitro VP4 capping activity. Only triple but not single substitution mutations of these residues in genome resulted in reduced virus replication kinetics. This is the first report investigating the importance of 2′-O MTase function for any member of the Reoviridae and highlights the significance of K-D-K-E tetrad and surrounding residues for the efficiency of 2′-O MTase activity and in turn, for virus fitness.",2015 Feb 24,"['Stewart, Meredith E.', 'Roy, Polly']",FEBS Open Bio,,,False
1e211bc0033ee7ea3f43bffa37f1b930c76ac188,PMC,Ebola virus disease: the ‘Black Swan’ in West Africa,http://dx.doi.org/10.1177/0049475514564269,PMC4361454,25527679,CC BY-NC,,2015 Jan,"['Brown, Colin', 'Arkell, Paul', 'Rokadiya, Sakib']",Trop Doct,,,True
e067126ec49ccefe14aad179c2c9d3e5b46b3c90,PMC,In this issue,,PMC4362136,,CC BY-NC-SA,,2014,,Saudi Med J,,,False
7aa307b2fa1b8d8aa3fa0a19abc0bd86c1c139cd,PMC,Viral etiology of respiratory infections in children in southwestern Saudi Arabia using multiplex reverse-transcriptase polymerase chain reaction,,PMC4362149,25399211,CC BY-NC-SA,"OBJECTIVES: To investigate 15 respiratory viruses in children with acute respiratory tract infections (ARTIs) using multiplex reverse-transcriptase polymerase chain reaction (RT-PCR), and to analyze the clinical and epidemiological features of these viruses. METHODS: In a cross-sectional study, 135 children, ≤5 years of age who presented with ARTIs in Najran Maternity and Children Hospital, Najran, Saudi Arabia between October 2012 and July 2013 were included. The clinical and sociodemographic data, and the laboratory results were recorded using a standardized questionnaire. Two nasopharyngeal swabs were collected from each child: one for bacteriological examination, and the second for viral detection using multiplex RT-PCR. RESULTS: A single viral pathogen was detected in 76 patients, viral coinfections in 9, and mixed viral and bacterial pathogens in 15. Respiratory syncytial virus was isolated in 33 patients, human rhinovirus (hRV) in 22, adenovirus (AdV) in 19, human metapneumovirus in 13, influenza virus in 10, parainfluenza virus in 7, human corona virus (hCoV) in 4, and human bocavirus in one. CONCLUSION: Respiratory syncytial virus, hRV, and AdV were the most frequent viruses, accounting for more than two-thirds of the cases. Other viruses, such as MPV, hCoV NL63, and hCoV OC43, may play a role in pediatric ARTIs. Of significance is the potential use of multiplex RT-PCR to provide epidemiological and virological data for early detection of the emergence of novel respiratory viruses in the era of the Middle East respiratory syndrome coronavirus.",2014,"['Al-Ayed, Mohamed S.', 'Asaad, Ahmed M.', 'Qureshi, Mohamed A.', 'Ameen, Mohammed S.']",Saudi Med J,,,True
8d5870809b9534c49bb0a3544de6a356b63d9a5a,PMC,Zoonoses in the Arabian Peninsula,,PMC4362160,25491209,CC BY-NC-SA,"The human population is rising and will soon reach 9 billion people. In parallel, the demand for animal protein is increasing and with it is the threat of zoonotic diseases. We must therefore be on our guard. The close association of people with animals promotes the opportunity for zoonotic infections and real danger may arise when animals are imported with no health background. Therefore, it is essential to implement strict import controls, and establish efficient quarantine facilities. Many viral, bacterial, and zoonotic diseases have been diagnosed on the Arabian Peninsula, either by isolating the pathogens or through serological surveys. Most of them are briefly discussed in this paper.",2014,"Wernery, Ulrich",Saudi Med J,,,True
07054fdca599b609a0fd99007a13a5133145449c,PMC,A rewarding 2014 for Saudi Medical Journal,http://dx.doi.org/10.15537/smj.2015.1.11318,PMC4362192,25629997,CC BY-NC-SA,,2015,"AlBarrak, Ali",Saudi Med J,,,True
f762eef06ad6975bb55dc425f10e33101d378379,PMC,Introduction of a point mutation into an HLA class I single-chain trimer induces enhancement of CTL priming and antitumor immunity,http://dx.doi.org/10.1038/mtm.2014.27,PMC4362367,26015969,CC BY-NC-SA,"We previously discovered one particular HLA-A*02:01 mutant that enhanced peptide-specific cytotoxic T lymphocyte (CTL) recognition in vitro compared to wild-type HLA-A*02:01. This mutant contains a single amino acid substitution from histidine to leucine at position 74 (H74L) that is located in the peptide-binding groove. To investigate the effect of the H74L mutation on the in vivo CTL priming, we took advantage of the technology of the HLA class I single-chain trimer (SCT) in which three components involving a peptide, β2 microglobulin and the HLA class I heavy chain are joined together via flexible linkers. We generated recombinant adenovirus expressing SCT comprised influenza A matrix protein (FMP)-derived peptide, β2 microglobulin and the H74L heavy chain. HLA-A*02:01 transgenic mice were immunized with the adenovirus, and the induction of peptide-specific CTLs and antitumor immunity was investigated. It was clearly shown that the H74L mutation enabled the HLA-A*02:01 SCT molecule to dramatically enhance both in vivo priming of FMP-specific CTLs and protection against a lethal challenge of tumor cells expressing FMP. These data present the first evidence that a simple point mutation in the HLA class I heavy chain of SCT is beneficial for improving CTL-based immunotherapy and prophylaxis to control tumors.",2014 Jul 2,"['Matsui, Masanori', 'Kawano, Masaaki', 'Matsushita, Sho', 'Akatsuka, Toshitaka']",Mol Ther Methods Clin Dev,,,True
9ddc6eddec3c91f53a24653e004620fad3a694ec,PMC,Aurintricarboxylic acid increases yield of HSV-1 vectors,http://dx.doi.org/10.1038/mtm.2013.6,PMC4365865,26015945,CC BY-NC-ND,"Production of large quantities of viral vectors is crucial for the success of gene therapy in the clinic. There is a need for higher titers of herpes simplex virus-1 (HSV-1) vectors both for therapeutic use as well as in the manufacturing of clinical grade adeno-associated virus (AAV) vectors. HSV-1 yield increased when primary human fibroblasts were treated with anti-inflammatory drugs like dexamethasone or valproic acid. In our search for compounds that would increase HSV-1 yield, we investigated another anti-inflammatory compound, aurintricarboxylic acid (ATA). Although ATA has been previously shown to have antiviral effects, we find that low (micromolar) concentrations of ATA increased HSV-1 vector production yields. Our results showing the use of ATA to increase HSV-1 titers have important implications for the production of certain HSV-1 vectors as well as recombinant AAV vectors.",2014 Feb 19,"['Pechan, Peter', 'Ardinger, Jeffery', 'Ketavarapu, Jyothi', 'Rubin, Hillard', 'Wadsworth, Samuel C', 'Scaria, Abraham']",Mol Ther Methods Clin Dev,,,True
86afebc58ebd3a14ab6d730d4c5fc32dc56ec3c5,PMC,Type 1 interferon gene transfer enhances host defense against pulmonary Streptococcus pneumoniae infection via activating innate leukocytes,http://dx.doi.org/10.1038/mtm.2014.5,PMC4378291,26015944,CC BY-NC-SA,"Pneumococcal infections are the leading cause of community-acquired pneumonia. Although the type 1 interferon-α (IFN-α) is a well-known antiviral cytokine, the role of IFN-α in antipneumococcal host defense and its therapeutic potential remain poorly understood. We have investigated these issues by using a murine transgene expression model. We found that in control animals, Streptococcus pneumoniae infection caused severe weight loss and excessive lung inflammation, associated with rapid bacterial outgrowth. In contrast, the animals that received a single dose of an adenoviral vector expressing IFN-α prior to pneumococcal infection demonstrated rapid and effective control of bacterial replication and lung inflammation and improved clinical outcome. Enhanced protection by IFN-α was due to increased activation of neutrophils and macrophages with increased release of reactive oxygen and nitrogen species and bacterial killing. Furthermore, we found that raised levels of IFN-α in the lung remained immune protective even when the gene transfer vector was given at a time postpneumococcal infection. Our study thus shows that the classically antiviral type 1 IFN can be exploited for enhancing immunity against pneumococcal infection via its activating effects on innate immune cells. Our findings hold implications for the therapeutic use of IFN-α gene transfer strategies to combat pneumococcal infections.",2014 Mar 19,"['Damjanovic, Daniela', 'Khera, Amandeep', 'Medina, Maria Fe', 'Ennis, Jane', 'Turner, Jeffrey D', 'Gauldie, Jack', 'Xing, Zhou']",Mol Ther Methods Clin Dev,,,True
59298b7755c89a0c0fdd694728739ca03f0d379f,PMC,Type 1 interferon gene transfer enhances host defense against pulmonary Streptococcus pneumoniae infection via activating innate leukocytes,http://dx.doi.org/10.1038/mtm.2014.5,PMC4378291,26015944,CC BY-NC-SA,"Pneumococcal infections are the leading cause of community-acquired pneumonia. Although the type 1 interferon-α (IFN-α) is a well-known antiviral cytokine, the role of IFN-α in antipneumococcal host defense and its therapeutic potential remain poorly understood. We have investigated these issues by using a murine transgene expression model. We found that in control animals, Streptococcus pneumoniae infection caused severe weight loss and excessive lung inflammation, associated with rapid bacterial outgrowth. In contrast, the animals that received a single dose of an adenoviral vector expressing IFN-α prior to pneumococcal infection demonstrated rapid and effective control of bacterial replication and lung inflammation and improved clinical outcome. Enhanced protection by IFN-α was due to increased activation of neutrophils and macrophages with increased release of reactive oxygen and nitrogen species and bacterial killing. Furthermore, we found that raised levels of IFN-α in the lung remained immune protective even when the gene transfer vector was given at a time postpneumococcal infection. Our study thus shows that the classically antiviral type 1 IFN can be exploited for enhancing immunity against pneumococcal infection via its activating effects on innate immune cells. Our findings hold implications for the therapeutic use of IFN-α gene transfer strategies to combat pneumococcal infections.",2014 Mar 19,"['Damjanovic, Daniela', 'Khera, Amandeep', 'Medina, Maria Fe', 'Ennis, Jane', 'Turner, Jeffrey D', 'Gauldie, Jack', 'Xing, Zhou']",Mol Ther Methods Clin Dev,,,False
b02e71f6059bdc0eb63e7e8999869e7c6e5c31fb,PMC,ITRACONAZOLE INHIBITS ENTEROVIRUS REPLICATION BY TARGETING THE OXYSTEROL-BINDING PROTEIN,http://dx.doi.org/10.1016/j.celrep.2014.12.054,PMC4383725,25640182,CC BY-NC,"Itraconazole (ITZ) is a well-known antifungal agent that also has anti-cancer activity. In this study, we identified ITZ as a broad-spectrum inhibitor of enteroviruses (e.g. poliovirus, coxsackievirus, enterovirus-71, rhinovirus). We demonstrate that ITZ inhibits viral RNA replication by targeting oxysterol-binding protein (OSBP) and OSBP-related protein 4 (ORP4). Consistently, OSW-1, a specific OSBP/ORP4 antagonist, also inhibits enterovirus replication. Knockdown of OSBP inhibits virus replication whereas overexpression of OSBP or ORP4 counteracts the antiviral effects of ITZ and OSW-1. ITZ binds OSBP and inhibits its function, i.e. shuttling of cholesterol and phosphatidylinositol-4-phosphate between membranes, thereby likely perturbing the virus-induced membrane alterations essential for viral replication organelle formation. ITZ also inhibits hepatitis C virus replication, which also relies on OSBP. Together, these data implicate OSBP/ORP4 as novel molecular targets of ITZ and point to an essential role of OSBP/ORP4-mediated lipid exchange in virus replication that can be targeted by antiviral drugs.",2015 Feb 3,"['Strating, Jeroen R.P.M.', 'van der Linden, Lonneke', 'Albulescu, Lucian', 'Bigay, Joëlle', 'Arita, Minetaro', 'Delang, Leen', 'Leyssen, Pieter', 'van der Schaar, Hilde M.', 'Lanke, Kjerstin H.W.', 'Thibaut, Hendrik Jan', 'Ulferts, Rachel', 'Drin, Guillaume', 'Schlinck, Nina', 'Wubbolts, Richard W.', 'Sever, Navdar', 'Head, Sarah A.', 'Liu, Jun O.', 'Beachy, Philip A.', 'De Matteis, Maria A.', 'Shair, Matthew D.', 'Olkkonen, Vesa M.', 'Neyts, Johan', 'van Kuppeveld, Frank J.M.']",Cell Rep,,,True
5d3cad66ff27b7d70f1895c653f79d63379af069,PMC,ITRACONAZOLE INHIBITS ENTEROVIRUS REPLICATION BY TARGETING THE OXYSTEROL-BINDING PROTEIN,http://dx.doi.org/10.1016/j.celrep.2014.12.054,PMC4383725,25640182,CC BY-NC,"Itraconazole (ITZ) is a well-known antifungal agent that also has anti-cancer activity. In this study, we identified ITZ as a broad-spectrum inhibitor of enteroviruses (e.g. poliovirus, coxsackievirus, enterovirus-71, rhinovirus). We demonstrate that ITZ inhibits viral RNA replication by targeting oxysterol-binding protein (OSBP) and OSBP-related protein 4 (ORP4). Consistently, OSW-1, a specific OSBP/ORP4 antagonist, also inhibits enterovirus replication. Knockdown of OSBP inhibits virus replication whereas overexpression of OSBP or ORP4 counteracts the antiviral effects of ITZ and OSW-1. ITZ binds OSBP and inhibits its function, i.e. shuttling of cholesterol and phosphatidylinositol-4-phosphate between membranes, thereby likely perturbing the virus-induced membrane alterations essential for viral replication organelle formation. ITZ also inhibits hepatitis C virus replication, which also relies on OSBP. Together, these data implicate OSBP/ORP4 as novel molecular targets of ITZ and point to an essential role of OSBP/ORP4-mediated lipid exchange in virus replication that can be targeted by antiviral drugs.",2015 Feb 3,"['Strating, Jeroen R.P.M.', 'van der Linden, Lonneke', 'Albulescu, Lucian', 'Bigay, Joëlle', 'Arita, Minetaro', 'Delang, Leen', 'Leyssen, Pieter', 'van der Schaar, Hilde M.', 'Lanke, Kjerstin H.W.', 'Thibaut, Hendrik Jan', 'Ulferts, Rachel', 'Drin, Guillaume', 'Schlinck, Nina', 'Wubbolts, Richard W.', 'Sever, Navdar', 'Head, Sarah A.', 'Liu, Jun O.', 'Beachy, Philip A.', 'De Matteis, Maria A.', 'Shair, Matthew D.', 'Olkkonen, Vesa M.', 'Neyts, Johan', 'van Kuppeveld, Frank J.M.']",Cell Rep,,,True
0167dddb0e2783a60841b8e6f2b4e4cb981904e2,PMC,Three cases of idiopathic eosinophilic enteritis with chronic obstinate diarrhea in Japanese Black fattening cattle,http://dx.doi.org/10.1292/jvms.14-0460,PMC4383781,25391396,CC BY-NC-ND,"Eosinophilic enteritis (EOE) is a type of inflammatory bowel disease and is characterized clinically by chronic obstinate diarrhea. Three Japanese Black (JB) fattening cattle (2 males and 1 female) on different cattle farms presented with chronic episodic diarrhea without fever or dehydration. Soft reddish spherical carneous tissues (1−3 cm) were occasionally excreted within the diarrheic feces. Administration of antibiotics, antidiarrheal drugs and vermicides had no therapeutic effect, but dexamethasone improved the fecal characteristics. The symptoms persisted until the animals were slaughtered at 27–30 months of age. Histopathological examination of the intestines revealed marked eosinophilic infiltration in the lamina propria and submucosa. From these findings, we diagnosed these cattle as the first cases of EOE in JB cattle.",2015 Mar 12,"['FUSHIMI, Yasuo', 'TAKAGI, Mitsuhiro', 'KAWAGUCHI, Hiroaki', 'MIYOSHI, Noriaki', 'TSUKA, Takeshi', 'DEGUCHI, Eisaburo']",J Vet Med Sci,,,True
8793343683237029bac548225ba51f403489cd35,PMC,Assessment of PaO(2)/FiO(2) for stratification of patients with moderate and severe acute respiratory distress syndrome,http://dx.doi.org/10.1136/bmjopen-2014-006812,PMC4386240,25818272,CC BY-NC,"OBJECTIVES: A recent update of the definition of acute respiratory distress syndrome (ARDS) proposed an empirical classification based on ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO(2)/FiO(2)) at ARDS onset. Since the proposal did not mandate PaO(2)/FiO(2) calculation under standardised ventilator settings (SVS), we hypothesised that a stratification based on baseline PaO(2)/FiO(2) would not provide accurate assessment of lung injury severity. DESIGN: A prospective, multicentre, observational study. SETTING: A network of teaching hospitals. PARTICIPANTS: 478 patients with eligible criteria for moderate (100<PaO(2)/FiO(2)≤200) and severe (PaO(2)/FiO(2)≤100) ARDS and followed until hospital discharge. INTERVENTIONS: We examined physiological and ventilator parameters in association with the PaO(2)/FiO(2) at ARDS onset, after 24 h of usual care and at 24 h under a SVS. At 24 h, patients were reclassified as severe, moderate, mild (200<PaO(2)/FiO(2)≤300) ARDS and non-ARDS (PaO(2)/FiO(2)>300). PRIMARY AND SECONDARY OUTCOMES: Group severity and hospital mortality. RESULTS: At ARDS onset, 173 patients had a PaO(2)/FiO(2)≤100 but only 38.7% met criteria for severe ARDS at 24 h under SVS. When assessed under SVS, 61.3% of patients with severe ARDS were reclassified as moderate, mild and non-ARDS, while lung severity and hospital mortality changed markedly with every PaO(2)/FiO(2) category (p<0.000001). Our model of risk stratification outperformed the stratification using baseline PaO(2)/FiO(2) and non-standardised PaO(2)/FiO(2) at 24 h, when analysed by the predictive receiver operating characteristic (ROC) curve: area under the ROC curve for stratification at baseline was 0.583 (95% CI 0.525 to 0.636), 0.605 (95% CI 0.552 to 0.658) at 24 h without SVS and 0.693 (95% CI 0.645 to 0.742) at 24 h under SVS (p<0.000001). CONCLUSIONS: Our findings support the need for patient assessment under SVS at 24 h after ARDS onset to assess disease severity, and have implications for the diagnosis and management of ARDS patients. TRIAL REGISTRATION NUMBERS: NCT00435110 and NCT00736892.",2015 Mar 27,"['Villar, Jesús', 'Blanco, Jesús', 'del Campo, Rafael', 'Andaluz-Ojeda, David', 'Díaz-Domínguez, Francisco J', 'Muriel, Arturo', 'Córcoles, Virgilio', 'Suárez-Sipmann, Fernando', 'Tarancón, Concepción', 'González-Higueras, Elena', 'López, Julia', 'Blanch, Lluis', 'Pérez-Méndez, Lina', 'Fernández, Rosa Lidia', 'Kacmarek, Robert M']",BMJ Open,,,True
8582184d3d2e497088f716ad0fa5bd49976f0dd3,PMC,The metagenomic approach and causality in virology,http://dx.doi.org/10.1590/S0034-8910.2015049005475,PMC4390074,25902566,CC BY-NC,"Nowadays, the metagenomic approach has been a very important tool in the discovery of new viruses in environmental and biological samples. Here we discuss how these discoveries may help to elucidate the etiology of diseases and the criteria necessary to establish a causal association between a virus and a disease.",2015 Apr 1,"['Castrignano, Silvana Beres', 'Nagasse-Sugahara, Teresa Keico']",Rev Saude Publica,,,True
a68da0099e002cdce53a89a826b412f7f8bb15d6,PMC,Balkan endemic nephropathy—current status and future perspectives,http://dx.doi.org/10.1093/ckj/sft049,PMC4400492,26064484,CC BY-NC,"Balkan endemic nephropathy (BEN), originally described in 1956, is a unique familial, chronic renal disease encountered with a high-prevalence rate in Serbia, Bulgaria, Romania, Croatia and Bosnia and Herzegovina. The most prominent features of the disease are its endemic nature, long-incubation period, familial clustering of the disease and an unusually high incidence of associated upper urothelial cancer (UUC). There are no clear-cut data on BEN incidence and prevalence, since the studies carried out in different endemic areas yielded contradictory information. In spite of intermittent variations, the incidence of new cases has remained stable over time. It has been estimated that almost 100 000 people are at risk of BEN, whereas 25 000 have the disease. The clinical signs and symptoms of BEN are non-specific and often remain unrecognized for years. There are no pathognomonic diagnostic features of BEN, but the set of epidemiological, clinical and biochemical data along with the pattern of pathologic injury in the absence of any other renal diseases are highly suggestive of this entity. Although the aetiology has been extensively studied, fostering the publication of various hypotheses, only one of them has provided conclusive evidence related to the aetiology of BEN. Studies conducted over the past decade have provided particularly strong arguments that BEN and UUC are caused by chronic poisoning with aristolochic acids (AAs). In light of these later studies, one can raise the question whether AAs could be responsible for previously and currently widespread unrecognized global renal disease and UUC.",2013 Jun,"Pavlović, Nikola M.",Clin Kidney J,,,True
15f57ae58cbfdd0616c570508ce0471bc4dacebe,PMC,Procalcitonin and C-reactive protein cannot differentiate bacterial or viral infection in COPD exacerbation requiring emergency department visits,http://dx.doi.org/10.2147/COPD.S76740,PMC4403815,25926728,CC BY-NC,"BACKGROUND: Viral and bacterial infections are the most common causes of chronic obstructive pulmonary disease (COPD) exacerbations. Whether serum inflammatory markers can differentiate bacterial from virus infection in patients with COPD exacerbation requiring emergency department (ED) visits remains controversial. METHODS: Viral culture and polymerase chain reaction (PCR) were used to identify the viruses in the oropharynx of patients with COPD exacerbations. The bacteria were identified by the semiquantitative culture of the expectorated sputum. The peripheral blood white blood cell (WBC) counts, serum C-reactive protein (CRP), procalcitonin (PCT), and clinical symptoms were compared among patients with different types of infections. RESULTS: Viruses were isolated from 16 (22.2%) of the 72 patients enrolled. The most commonly identified viruses were parainfluenza type 3, influenza A, and rhinovirus. A total of 30 (41.7%) patients had positive bacterial cultures, with the most commonly found bacteria being Haemophilus influenzae and Haemophilus parainfluenzae. Five patients (6.9%) had both positive sputum cultures and virus identification. The WBC, CRP, and PCT levels of the bacteria-positive and bacteria-negative groups were not statistically different. Multivariate analysis showed that patients with increased sputum volumes during the COPD exacerbations had higher risks of recurrent exacerbations in the 1-year period following the first exacerbation. CONCLUSION: WBC, CRP, or PCT could not differentiate between bacterial and viral infections in patients with COPD exacerbation requiring ED visits. Those with increased sputum during a COPD exacerbation had higher risks for recurrent exacerbations.",2015 Apr 13,"['Chang, Chih-Hao', 'Tsao, Kuo-Chien', 'Hu, Han-Chung', 'Huang, Chung-Chi', 'Kao, Kuo-Chin', 'Chen, Ning-Hung', 'Yang, Cheng-Ta', 'Tsai, Ying-Huang', 'Hsieh, Meng-Jer']",Int J Chron Obstruct Pulmon Dis,,,True
6e4cdb85e0a4e9f66a92f231bba4bb3b91f9f822,PMC,New global viral threats,http://dx.doi.org/10.15537/smj.2015.4.10089,PMC4404471,25828274,CC BY-NC-SA,"Infectious diseases have caused great catastrophes in human history, as in the example of the plague, which wiped out half of the population in Europe in the 14th century. Ebola virus and H7N9 avian influenza virus are 2 lethal pathogens that we have encountered in the second decade of the 21st century. Ebola infection is currently being seen in West Africa, and H7N9 avian flu appears to have settled in Southeast Asia. This article focuses on the current situation and the future prospects of these potential infectious threats to mankind.",2015,"['Erdem, Hakan', 'Ünal, Serhat']",Saudi Med J,,,True
30c0e6db2173676aae3b5a5fcdf9243903c536c1,PMC,Evaluation of knowledge and behavior of workers in Prince Mohammed International Airport in Western Saudi Arabia regarding public health emergency measures applied during Hajj season 2014,http://dx.doi.org/10.15537/smj.2015.4.10908,PMC4404480,25828283,CC BY-NC-SA,"OBJECTIVES: To evaluate the knowledge and behavior of workers at a Saudi airport regarding public health emergency measures applied during Hajj season. METHODS: This study is a cross-sectional study conducted at the Prince Mohammed International Airport in Al-Madinah Al-Munawwarah, Saudi Arabia between August and September 2014. Data were collected by semi-structured questionnaires during personal interviews. Non-random purposive sampling was conducted to target workers at higher risk of acquiring infection from travellers. RESULTS: One hundred and eighty-six participants were recruited of whom 92.5% were males. The study participants were workers in 8 different sectors. Twenty-six percent of the participants were health workers. Non-health workers were more likely to be concerned on acquiring infection while working at the airport compared with health workers (p=0.023). The most commonly feared disease was Ebola viral disease (EBV) among 30% of health workers, and 47% of non-health workers. Approximately 47% of non-health workers reported no knowledge of the procedures implemented during public health emergencies. The proportion of participants who received public health related training among non-health workers was significantly lower compared with health workers (p<0.00001). CONCLUSION: More emphasis should be given to educating airport workers on the potential health threats at the airport. Specific guidelines for public health emergencies at the airport should be established and communicated with airport sectors.",2015,"['Gosadi, Ibrahim M.', 'Al-Hazmi, Ali M.', 'Fadl, Amin A.', 'Alharbi, Khalid H.', 'Swarelzahab, Mazin M.']",Saudi Med J,,,True
49fb495cd0efde647aa99ec56606432699b1e88e,PMC,Middle East respiratory syndrome coronavirus in children,http://dx.doi.org/10.15537/smj.2015.4.10243,PMC4404484,25828287,CC BY-NC-SA,"The Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV). The disease is reported mainly in adults. Data in children are scarce. The disease caused by MERS-CoV in children presents with a wide range of clinical manifestations, and it is associated with a lower mortality rate compared with adults. Poor outcome is observed mainly in admitted patients with medical comorbidities. We report a new case of MERS-CoV infection in a 9-month-old child complicated by severe respiratory symptoms, multi-organ dysfunction, and death. We reviewed the literature in an attempt to characterize the mode of presentation, the risk factors, and outcome of MERS-CoV infection in the pediatric population.",2015,"['Thabet, Farah', 'Chehab, May', 'Bafaqih, Hind', 'AlMohaimeed, Sulaiman']",Saudi Med J,,,True
c63f31f1d46c5a3cd4d4f2baeab9ce8c3a1dd3bf,PMC,Recent Advances of Vaccine Adjuvants for Infectious Diseases,http://dx.doi.org/10.4110/in.2015.15.2.51,PMC4411509,25922593,CC BY-NC,"Vaccines are the most effective and cost-efficient method for preventing diseases caused by infectious pathogens. Despite the great success of vaccines, development of safe and strong vaccines is still required for emerging new pathogens, re-emerging old pathogens, and in order to improve the inadequate protection conferred by existing vaccines. One of the most important strategies for the development of effective new vaccines is the selection and usage of a suitable adjuvant. Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Thus, formulation of vaccines with appropriate adjuvants is an attractive approach towards eliciting protective and long-lasting immunity in humans. However, only a limited number of adjuvants is licensed for human vaccines due to concerns about safety and toxicity. We summarize current knowledge about the potential benefits of adjuvants, the characteristics of adjuvants and the mechanisms of adjuvants in human vaccines. Adjuvants have diverse modes of action and should be selected for use on the basis of the type of immune response that is desired for a particular vaccine. Better understanding of current adjuvants will help exploring new adjuvant formulations and facilitate rational design of vaccines against infectious diseases.",2015 Apr 23,"['Lee, Sujin', 'Nguyen, Minh Trang']",Immune Netw,,,True
611a37c75e97cd0e251685d63fbbb42dbe3827b9,PMC,An H5N1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with H7N9 influenza virus,http://dx.doi.org/10.1038/emi.2015.22,PMC4417706,26038770,CC BY-NC-SA,"In March 2013, a patient infected with a novel avian influenza A H7N9 virus was reported in China. Since then, there have been 458 confirmed infection cases and 177 deaths. The virus contains several human-adapted markers, indicating that H7N9 has pandemic potential. The outbreak of this new influenza virus highlighted the need for the development of universal influenza vaccines. Previously, we demonstrated that a tetrameric peptide vaccine based on the matrix protein 2 ectodomain (M2e) of the H5N1 virus (H5N1-M2e) could protect mice from lethal infection with different clades of H5N1 and 2009 pandemic H1N1 influenza viruses. In this study, we investigated the cross-protection of H5N1-M2e against lethal infection with the new H7N9 virus. Although five amino acid differences existed at positions 13, 14, 18, 20, and 21 between M2e of H5N1 and H7N9, H5N1-M2e vaccination with either Freund's adjuvant or the Sigma adjuvant system (SAS) induced a high level of anti-M2e antibody, which cross-reacted with H7N9-M2e peptide. A mouse-adapted H7N9 strain, A/Anhui/01/2013m, was used for lethal challenge in animal experiments. H5N1-M2e vaccination provided potent cross-protection against lethal challenge of the H7N9 virus. Reduced viral replication and histopathological damage of mouse lungs were also observed in the vaccinated mice. Our results suggest that the tetrameric H5N1-M2e peptide vaccine could protect against different subtypes of influenza virus infections. Therefore, this vaccine may be an ideal candidate for developing a universal vaccine to prevent the reemergence of avian influenza A H7N9 virus and the emergence of potential novel reassortants of influenza virus.",2015 Apr 8,"['Leung, Ho-Chuen', 'Chan, Chris Chung-Sing', 'Poon, Vincent Kwok-Man', 'Zhao, Han-Jun', 'Cheung, Chung-Yan', 'Ng, Fai', 'Huang, Jian-Dong', 'Zheng, Bo-Jian']",Emerg Microbes Infect,,,True
933b17f79aad3485aa3e1d489a7a89ea0ae94a66,PMC,A cluster randomised trial of cloth masks compared with medical masks in healthcare workers,http://dx.doi.org/10.1136/bmjopen-2014-006577,PMC4420971,25903751,CC BY-NC,"OBJECTIVE: The aim of this study was to compare the efficacy of cloth masks to medical masks in hospital healthcare workers (HCWs). The null hypothesis is that there is no difference between medical masks and cloth masks. SETTING: 14 secondary-level/tertiary-level hospitals in Hanoi, Vietnam. PARTICIPANTS: 1607 hospital HCWs aged ≥18 years working full-time in selected high-risk wards. INTERVENTION: Hospital wards were randomised to: medical masks, cloth masks or a control group (usual practice, which included mask wearing). Participants used the mask on every shift for 4 consecutive weeks. MAIN OUTCOME MEASURE: Clinical respiratory illness (CRI), influenza-like illness (ILI) and laboratory-confirmed respiratory virus infection. RESULTS: The rates of all infection outcomes were highest in the cloth mask arm, with the rate of ILI statistically significantly higher in the cloth mask arm (relative risk (RR)=13.00, 95% CI 1.69 to 100.07) compared with the medical mask arm. Cloth masks also had significantly higher rates of ILI compared with the control arm. An analysis by mask use showed ILI (RR=6.64, 95% CI 1.45 to 28.65) and laboratory-confirmed virus (RR=1.72, 95% CI 1.01 to 2.94) were significantly higher in the cloth masks group compared with the medical masks group. Penetration of cloth masks by particles was almost 97% and medical masks 44%. CONCLUSIONS: This study is the first RCT of cloth masks, and the results caution against the use of cloth masks. This is an important finding to inform occupational health and safety. Moisture retention, reuse of cloth masks and poor filtration may result in increased risk of infection. Further research is needed to inform the widespread use of cloth masks globally. However, as a precautionary measure, cloth masks should not be recommended for HCWs, particularly in high-risk situations, and guidelines need to be updated. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry: ACTRN12610000887077.",2015 Apr 22,"['MacIntyre, C Raina', 'Seale, Holly', 'Dung, Tham Chi', 'Hien, Nguyen Tran', 'Nga, Phan Thi', 'Chughtai, Abrar Ahmad', 'Rahman, Bayzidur', 'Dwyer, Dominic E', 'Wang, Quanyi']",BMJ Open,,,True
78dc2abf39a665aec9b4a48738a2b4b838bfe72e,PMC,"Dieckol, a Component of Ecklonia cava, Suppresses the Production of MDC/CCL22 via Down-Regulating STAT1 Pathway in Interferon-γ Stimulated HaCaT Human Keratinocytes",http://dx.doi.org/10.4062/biomolther.2014.141,PMC4428716,25995822,CC BY-NC,"Macrophage-derived chemokine, C-C motif chemokine 22 (MDC/CCL22), is one of the inflammatory chemokines that controls the movement of monocytes, monocyte-derived dendritic cells, and natural killer cells. Serum and skin MDC/CCL22 levels are elevated in atopic dermatitis, which suggests that the chemokines produced from keratinocytes are responsible for attracting inflammatory lymphocytes to the skin. A major signaling pathway in the interferon-γ (IFN-γ)-stimulated inflammation response involves the signal transducers and activators of transcription 1 (STAT1). In the present study, we investigated the anti-inflammatory effect of dieckol and its possible action mechanisms in the category of skin inflammation including atopic dermatitis. Dieckol inhibited MDC/CCL22 production induced by IFN-γ (10 ng/mL) in a dose dependent manner. Dieckol (5 and 10 μM) suppressed the phosphorylation and the nuclear translocation of STAT1. These results suggest that dieckol exhibits anti-inflammatory effect via the down-regulation of STAT1 activation.",2015 May 1,"['Kang, Na-Jin', 'Koo, Dong-Hwan', 'Kang, Gyeoung-Jin', 'Han, Sang-Chul', 'Lee, Bang-Won', 'Koh, Young-Sang', 'Hyun, Jin-Won', 'Lee, Nam-Ho', 'Ko, Mi-Hee', 'Kang, Hee-Kyoung', 'Yoo, Eun-Sook']",Biomol Ther (Seoul),,,True
8b9992937c24368f15eb03e7009ba85beadab1e2,PMC,Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial,http://dx.doi.org/10.1093/cid/civ065,PMC4429758,25673560,CC BY-NC-ND,"Background. The high burden of respiratory syncytial virus (RSV)-associated morbidity and mortality makes vaccine development a priority. Methods. As part of an efficacy trial of pandemic influenza vaccines (NCT01051661), RSV epidemiology in healthy children aged 6 months to <10 years at first vaccination with influenza-like illness (ILI) was evaluated in Australia, Brazil, Colombia, Costa Rica, Mexico, the Philippines, Singapore, and Thailand between February 2010 and August 2011. Active surveillance for ILI was conducted for approximately 1 year, with nasal and throat swabs analyzed by polymerase chain reaction. The prevalence and incidence of RSV among ILI episodes were calculated. Results. A total of 6266 children were included, of whom 2421 experienced 3717 ILI episodes with a respiratory sample available. RSV was detected for 359 ILI episodes, a prevalence of 9.7% (95% confidence interval: 8.7–10.7). The highest prevalence was in children aged 12–23 or 24–35 months in all countries except the Philippines, where it was in children aged 6–11 months. The incidence of RSV-associated ILI was 7.0 (6.3–7.7) per 100 person-years (PY). Eighty-eight ILI episodes resulted in hospitalization, of which 8 were associated with RSV (prevalence 9.1% [4.0–17.1]; incidence 0.2 [0.1–0.3] per 100 PY). The incidence of RSV-associated ILI resulting in medical attendance was 6.0 (5.4–6.7) per 100 PY. RSV B subtypes were observed more frequently than A subtypes. Conclusions. Active surveillance demonstrated the considerable burden of RSV-associated illness that would not be identified through hospital-based surveillance, with a substantial part of the burden occurring in older infants and children.",2015 Jun 1,"['Nolan, Terry', 'Borja-Tabora, Charissa', 'Lopez, Pio', 'Weckx, Lily', 'Ulloa-Gutierrez, Rolando', 'Lazcano-Ponce, Eduardo', 'Kerdpanich, Angkool', 'Weber, Miguel Angel Rodriguez', 'Mascareñas de Los Santos, Abiel', 'Tinoco, Juan-Carlos', 'Safadi, Marco Aurelio P.', 'Seng, Lim Fong', 'Hernandez-de Mezerville, Marcela', 'Faingezicht, Idis', 'Cruz-Valdez, Aurelio', 'Feng, Yang', 'Li, Ping', 'Durviaux, Serge', 'Haars, Gerco', 'Roy-Ghanta, Sumita', 'Vaughn, David W.', 'Taylor, Sylvia']",Clin Infect Dis,,,True
32412ffe52eb41da8ecfed314b703c49fd041f5c,PMC,"Seasonality, ambient temperatures and hospitalizations for acute exacerbation of COPD: a population-based study in a metropolitan area",http://dx.doi.org/10.2147/COPD.S75710,PMC4431472,26056439,CC BY-NC,"BACKGROUND: Excluding the tropics, exacerbations of chronic obstructive pulmonary disease (COPD) are more frequent in winter. However, studies that directly relate hospitalizations for exacerbation of COPD to ambient temperature are lacking. The aim of this study was to assess the influence of temperature on the number of hospitalizations for COPD. METHODS: This was a population-based study in a metropolitan area. All hospital discharges for acute exacerbation of COPD during 2009 in Barcelona and its metropolitan area were analyzed. The relationship between the number of hospitalizations for COPD and the mean, minimum, and maximum temperatures alongside comorbidity, humidity, influenza rate, and environmental pollution were studied. RESULTS: A total of 9,804 hospitalization discharges coded with COPD exacerbation as a primary diagnosis were included; 75.4% of cases were male with a mean age of 74.9±10.5 years and an average length of stay of 6.5±6.1 days. The highest number of admissions (3,644 [37.2%]) occurred during winter, followed by autumn with 2,367 (24.1%), spring with 2,347 (23.9%), and summer with 1,446 (14.7%; P<0.001). The maximum, minimum, and mean temperatures were associated similarly with the number of hospitalizations. On average, we found that for each degree Celsius decrease in mean weekly temperature, hospital admissions increased by 5.04% (r(2)=0.591; P<0.001). After adjustment for humidity, comorbidity, air pollution, and influenza-like illness, only mean temperatures retained statistical significance, with a mean increase of 4.7% in weekly admissions for each degree Celsius of temperature (r(2)=0.599, P<0.001). CONCLUSION: Mean temperatures are closely and independently related to the number of hospitalizations for COPD.",2015 May 8,"['Almagro, Pere', 'Hernandez, Carme', 'Martinez-Cambor, Pable', 'Tresserras, Ricard', 'Escarrabill, Joan']",Int J Chron Obstruct Pulmon Dis,,,True
11a6f813fa996f0baa670ecc66875602f971eef1,PMC,Cytomegalovirus pneumonia as the first manifestation of severe combined immunodeficiency,http://dx.doi.org/10.5114/ceji.2014.45953,PMC4440000,26155153,CC BY-NC-ND,"Severe combined immunodeficiency (SCID) is characterized by the absence of functional T lymphocytes and impairment of adaptive immunity. While heterogeneity of the genetic background in SCID leads to the variability of immune phenotypes, most of affected newborns appear healthy but within the first few months they develop life-threatening opportunistic respiratory or gastrointestinal tract infections. The objective of the study was to define the presenting features and etiology of infections in children with SCID. We retrospectively reviewed five children in whom the diagnosis of SCID had been established in our pediatric immunology clinic over the last 10-year period. A viral respiratory tract infection was the first manifestation of SCID in all the children studied. Cytomegalovirus (CMV) pneumonia was recognized in as many as 4 cases and coronavirus pulmonary infection was diagnosed in one case, whereas Pneumocystis jiroveci was identified as a co-pathogen in one CMV-infected patient. Severe combined immunodeficiency is a pediatric emergency condition and given the significant impact of pulmonary CMV infection in SCID children, establishing an accurate etiological diagnosis is of essential importance in instituting the specific treatment and improving the outcome.",2014 Oct 14,"['Szczawińska-Popłonyk, Aleksandra', 'Jończyk-Potoczna, Katarzyna', 'Ossowska, Lidia', 'Bręborowicz, Anna', 'Bartkowska-Śniatkowska, Alicja', 'Wachowiak, Jacek']",Cent Eur J Immunol,,,True
a6436446abe06cc9a0991752d5cabad51f6b0d7e,PMC,"Community Case Clusters of Middle East Respiratory Syndrome Coronavirus in Hafr Al-Batin, Kingdom of Saudi Arabia: A Descriptive Genomic study",http://dx.doi.org/10.1016/j.ijid.2014.03.1372,PMC4441753,24699184,CC BY-NC-SA,"The Middle East respiratory syndrome coronavirus (MERS-CoV) was first described in September 2012 and to date 86 deaths from a total of 206 cases of MERS-CoV infection have been reported to the WHO. Camels have been implicated as the reservoir of MERS-CoV, but the exact source and mode of transmission for most patients remain unknown. During a 3 month period, June to August 2013, there were 12 positive MERS-CoV cases reported from the Hafr Al-Batin region district in the north east region of the Kingdom of Saudi Arabia. In addition to the different regional camel festivals in neighboring countries, Hafr Al-Batin has the biggest camel market in the entire Kingdom and hosts an annual camel festival. Thus, we conducted a detailed epidemiological, clinical and genomic study to ascertain common exposure and transmission patterns of all cases of MERS-CoV reported from Hafr Al-Batin. Analysis of previously reported genetic data indicated that at least two of the infected contacts could not have been directly infected from the index patient and alternate source should be considered. While camels appear as the likely source, other sources have not been ruled out. More detailed case control studies with detailed case histories, epidemiological information and genomic analysis are being conducted to delineate the missing pieces in the transmission dynamics of MERS-CoV outbreak.",2014 Jun,"['Memish, Ziad A.', 'Cotten, Matthew', 'Watson, Simon J.', 'Kellam, Paul', 'Zumla, Alimuddin', 'Alhakeem, Rafat F.', 'Assiri, Abdullah', 'Rabeeah, Abdullah A. Al', 'Al-Tawfiq, Jaffar A.']",Int J Infect Dis,,,False
d132c2b351eee236fe4f5c1c06bf90bd75ade661,PMC,Interferon-induced transmembrane protein-3 rs12252-C is associated with rapid progression of acute HIV-1 infection in Chinese MSM cohort,http://dx.doi.org/10.1097/QAD.0000000000000632,PMC4442129,25784441,CC BY-NC,"BACKGROUND: The interferon-inducible transmembrane protein-3 (IFITM3) is a protein that restricts multiple pathogenic viruses such as influenza virus. The single-nucleotide polymorphism rs12252-C, which is rare in Caucasian populations, but much more common in the Han Chinese population, has been found in much higher homozygous frequency in patients with severe acute influenza. Until now, there has been no study on the effect of this genetic variant on the clinical control of other viral infections. OBJECTIVES: To investigate the impact of IFITM3-rs12252 genotypes on primary HIV-1 infection progression in an acute HIV-1-infected cohort in Beijing (PRIMO), China. DESIGN AND METHODS: We identified IFITM3-rs12252 genotypes of 178 acute HIV-1-infected patients and 196 HIV-negative candidates from the PRIMO cohort. HIV-1 viral load and CD4(+) T-cell counts were monitored at multiple time points during the first year of infection, and the association between IFITM3-rs12252 genotype and disease progression was evaluated. RESULTS: The current study shows that the IFITM3-rs12252 genetic variant affects the progression of HIV-1 infection, but not the acquisition. A significantly higher frequency of the CC/CT genotypes was found in rapid progressors compared to nonprogressors. Patients with CC/CT genotypes showed an elevated peak viremia level and significantly lower CD4(+) T-cell count at multiple time points during the first year of primary infection, and a significantly higher risk of rapid decline of the CD4(+) T-cell count to below 350 cells/μl. CONCLUSION: A novel association between IFITM3 gene polymorphism and rapid disease progression is reported in an acute HIV-1-infected MSM cohort in China.",2015 May 15,"['Zhang, Yonghong', 'Makvandi-Nejad, Shokouh', 'Qin, Ling', 'Zhao, Yan', 'Zhang, Tong', 'Wang, Lili', 'Repapi, Emmanouela', 'Taylor, Stephen', 'McMichael, Andrew', 'Li, Ning', 'Dong, Tao', 'Wu, Hao']",AIDS,,,True
e1253d2bfe05e4fa4a42f9a542ca45c32a1e2264,PMC,A Novel Pathogenic Mammalian Orthoreovirus from Diarrheic Pigs and Swine Blood Meal in the United States,http://dx.doi.org/10.1128/mBio.00593-15,PMC4442135,25991685,CC BY-NC-SA,"Since May 2013, outbreaks of porcine epidemic diarrhea have devastated the U.S. swine industry, causing immense economic losses. Two different swine enteric coronaviruses (porcine epidemic diarrhea virus and Delta coronavirus) have been isolated from the affected swine population. The disease has been reported from at least 32 states of the United States and other countries, including Mexico, Peru, Dominican Republic, Canada, Columbia, Ecuador, and Ukraine, with repeated outbreaks in previously infected herds. Here we report the isolation and characterization of a novel mammalian orthoreovirus 3 (MRV3) from diarrheic feces of piglets from these outbreaks in three states and ring-dried swine blood meal from multiple sources. MRV3 could not be isolated from healthy or pigs that had recovered from epidemic diarrhea from four states. Several MRV3 isolates were obtained from chloroform-extracted pig feces or blood meal in cell cultures or developing chicken embryos. Biological characterization of two representative isolates revealed trypsin resistance and thermostability at 90°C. NextGen sequencing of ultrapurified viruses indicated a strong homology of the S1 segment to mammalian and bat MRV3. Neonatal piglets experimentally infected with these viruses or a chloroform extract of swine blood meal developed severe diarrhea and acute gastroenteritis with 100% mortality within 3 days postinfection. Therefore, the novel porcine MRV3 may contribute to enteric disease along with other swine enteric viruses. The role of MRV3 in the current outbreaks of porcine epidemic diarrhea in the United States remains to be determined, but the pathogenic nature of the virus warrants further investigations on its epidemiology and prevalence.",2015 May 19,"['Thimmasandra Narayanappa, Athmaram', 'Sooryanarain, Harini', 'Deventhiran, Jagadeeswaran', 'Cao, Dianjun', 'Ammayappan Venkatachalam, Backiyalakshmi', 'Kambiranda, Devaiah', 'LeRoith, Tanya', 'Heffron, Connie Lynn', 'Lindstrom, Nicole', 'Hall, Karen', 'Jobst, Peter', 'Sexton, Cary', 'Meng, Xiang-Jin', 'Elankumaran, Subbiah']",mBio,,,True
2823d7523188f052070c565fc1e5b9c35899f658,PMC,Relationship between the Clinical Characteristics and Intervention Scores of Infants with Apparent Life-threatening Events,http://dx.doi.org/10.3346/jkms.2015.30.6.763,PMC4444478,26028930,CC BY-NC,"We investigated the clinical presentations, diagnostic and therapeutic modalities, and prognosis from follow-up of infants with apparent life-threatening events (ALTE). In addition, the relationship between the clinical characteristics of patients and significant intervention scores was analyzed. We enrolled patients younger than 12 months who were diagnosed with ALTE from January 2005 to December 2012. There were 29 ALTE infants with a peak incidence of age younger than 1 month (48.3%). The most common symptoms for ALTE diagnosis were apnea (69.0%) and color change (58.6%). Eleven patients appeared normal upon arrival at hospital but 2 patients required cardiopulmonary resuscitation during the initial ALTE. The most common ALTE cause was respiratory disease, including respiratory infection and upper airway anomalies (44.8%). There were 20 cases of repeat ALTE and 2 cases of death during hospitalization. Four patients (15.4%) experienced recurrence of ALTE after discharge and 4 patients (15.4%) showed developmental abnormalities during the follow-up period. The patients with ALTE during sleep had lower significant intervention scores (P=0.015) compared to patients with ALTE during wakefulness and patients with previous respiratory symptoms had higher significant intervention scores (P=0.013) than those without previous respiratory symptoms. Although not statistically significant, there was a weak positive correlation between the patient's total ALTE criteria and total significant intervention score (Fig. 2, r=0.330, P=0.080). We recommend that all ALTE infants undergo inpatient observation and evaluations with at least 24 hr of cardiorespiratory monitoring, and should follow up at least within a month after discharge. GRAPHICAL ABSTRACT: [Image: see text]",2015 Jun 13,"['Choi, Hee Joung', 'Kim, Yeo Hyang']",J Korean Med Sci,,,True
dcce6e45fd562d7a15633fc5a55aed8d3ce37f49,PMC,Toll-Like Receptor 3 Signaling via TRIF Contributes to a Protective Innate Immune Response to Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/mBio.00638-15,PMC4447251,26015500,CC BY-NC-SA,"Toll-like receptors (TLRs) are sensors that recognize molecular patterns from viruses, bacteria, and fungi to initiate innate immune responses to invading pathogens. The emergence of highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) is a concern for global public health, as there is a lack of efficacious vaccine platforms and antiviral therapeutic strategies. Previously, it was shown that MyD88, an adaptor protein necessary for signaling by multiple TLRs, is a required component of the innate immune response to mouse-adapted SARS-CoV infection in vivo. Here, we demonstrate that TLR3(−/−), TLR4(−/−), and TRAM(−/−) mice are more susceptible to SARS-CoV than wild-type mice but experience only transient weight loss with no mortality in response to infection. In contrast, mice deficient in the TLR3/TLR4 adaptor TRIF are highly susceptible to SARS-CoV infection, showing increased weight loss, mortality, reduced lung function, increased lung pathology, and higher viral titers. Distinct alterations in inflammation were present in TRIF(−/−) mice infected with SARS-CoV, including excess infiltration of neutrophils and inflammatory cell types that correlate with increased pathology of other known causes of acute respiratory distress syndrome (ARDS), including influenza virus infections. Aberrant proinflammatory cytokine, chemokine, and interferon-stimulated gene (ISG) signaling programs were also noted following infection of TRIF(−/−) mice that were similar to those seen in human patients with poor disease outcome following SARS-CoV or MERS-CoV infection. These findings highlight the importance of TLR adaptor signaling in generating a balanced protective innate immune response to highly pathogenic coronavirus infections.",2015 May 26,"['Totura, Allison L.', 'Whitmore, Alan', 'Agnihothram, Sudhakar', 'Schäfer, Alexandra', 'Katze, Michael G.', 'Heise, Mark T.', 'Baric, Ralph S.']",mBio,,,True
3424dfd56dfdf957d0fca5e02da73f1352b84ca0,PMC,The role of C5a in acute lung injury induced by highly pathogenic viral infections,http://dx.doi.org/10.1038/emi.2015.28,PMC4451266,26060601,CC BY-NC-SA,"The complement system, an important part of innate immunity, plays a critical role in pathogen clearance. Unregulated complement activation is likely to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by highly pathogenic virus including influenza A viruses H5N1, H7N9, and severe acute respiratory syndrome (SARS) coronavirus. In highly pathogenic virus-induced acute lung diseases, high levels of chemotactic and anaphylatoxic C5a were produced as a result of excessive complement activaiton. Overproduced C5a displays powerful biological activities in activation of phagocytic cells, generation of oxidants, and inflammatory sequelae named “cytokine storm”, and so on. Blockade of C5a signaling have been implicated in the treatment of ALI induced by highly pathogenic virus. Herein, we review the literature that links C5a and ALI, and review our understanding of the mechanisms by which C5a affects ALI during highly pathogenic viral infection. In particular, we discuss the potential of the blockade of C5a signaling to treat ALI induced by highly pathogenic viruses.",2015 May 6,"['Wang, Renxi', 'Xiao, He', 'Guo, Renfeng', 'Li, Yan', 'Shen, Beifen']",Emerg Microbes Infect,,,True
74b7e481670a3a785ee8f82702d4be3b5488eb88,PMC,A Flood of Health Functional Foods: What Is to Be Recommended?,http://dx.doi.org/10.6118/jmm.2015.21.1.12,PMC4452808,26046032,CC BY-NC,"Health functional food is referred to a food prepared or processed from specific components or ingredients for functionality beneficial to the body through extraction, concentration, purification, blending and other methods. The demand for health functional foods is steadily increasing, and red ginseng is the most demanded food among women in the 50s, followed by multivitamin, omega-3, glucosamine and aloe. To date, there is insufficient evidence on the effect of red ginseng on exercise capacity, somatic symptom and cognitive performance in healthy individuals. Moreover, evidence is insufficient that a nutritional dose of vitamin or mineral reduces the incidence of cardiovascular disease and cancer, or mortality rate. A steady intake of oily fish is recommended to prevent the incidence of cardiovascular disease for postmenopausal women. Consumption of omega-3 fatty acids is expected to prevent cardiovascular disease in postmenopausal women with almost no intake of oily fish and those not taking statins. It still remains controversial whether glucosamine is effective in the treatment of osteoarthritis. Hence, physicians should fully inform patients with all controversial information about the effectiveness of glucosamine when prescribing glucosamine for patients with osteoarthritis.",2015 Apr 27,"Lee, Eun Sil",J Menopausal Med,,,True
9171b9ab69fa99aa5528c2173d4bf414c6d8c9cb,PMC,Reply to “Comments on Fouchier’s Calculation of Risk and Elapsed Time for Escape of a Laboratory-Acquired Infection from His Laboratory”,http://dx.doi.org/10.1128/mBio.00407-15,PMC4453508,25873379,CC BY-NC-SA,,2015 Apr 14,"Fouchier, Ron A. M.",mBio,,,True
64b6854e48706ee2c77c4450292e72d11b7e4252,PMC,The Importance of Virology at a Time of Great Need and Great Jeopardy,http://dx.doi.org/10.1128/mBio.00236-15,PMC4453524,25759503,CC BY-NC-SA,,2015 Mar 10,"['Imperiale, Michael J.', 'Casadevall, Arturo']",mBio,,,True
1376526470f18216200ecd6c375d9913942fa362,PMC,"Origin, Evolution, and Virulence of Porcine Deltacoronaviruses in the United States",http://dx.doi.org/10.1128/mBio.00064-15,PMC4453528,25759498,CC BY-NC-SA,"A novel porcine deltacoronavirus (PdCV) was first discovered in Ohio and Indiana in February 2014, rapidly spread to other states in the United States and Canada, and caused significant economic loss in the swine industry. The origin and virulence of this novel porcine coronavirus are not known. Here, we characterized U.S. PdCV isolates and determined their virulence in gnotobiotic and conventional piglets. Genome analyses revealed that U.S. PdCV isolates possess unique genetic characteristics and share a close relationship with Hong Kong and South Korean PdCV strains and coronaviruses (CoVs) of Asian leopard cats and Chinese ferret-badgers. The PdCV-positive intestinal content (Ohio CVM1) and the cell culture-adapted PdCV Michigan (MI) strain were orally inoculated into gnotobiotic and/or conventional piglets. Within 1 to 3 days postinfection, profuse watery diarrhea, vomiting, and dehydration were observed. Clinical signs were associated with epithelial necrosis in the gastric pits and small intestine, the latter resulting in severe villous atrophy. Mild interstitial pneumonia was identified in the lungs of PdCV-infected piglets. High levels of viral RNA (8 to 11 log RNA copies/g) were detected in intestinal tissues/luminal contents and feces of infected piglets, whereas moderate RNA levels (2 to 5 log RNA copies/g) were detected in blood, lung, liver, and kidney, indicating multisystemic dissemination of the virus. Polyclonal immune serum against PdCV but not immune serum against porcine epidemic diarrhea virus (PEDV) reacted with PdCV-infected small-intestinal epithelial cells, indicating that PdCV is antigenically distinct from PEDV. Collectively, we demonstrate for the first time that PdCV caused severe gastrointestinal diseases in swine.",2015 Mar 10,"['Ma, Yuanmei', 'Zhang, Yu', 'Liang, Xueya', 'Lou, Fangfei', 'Oglesbee, Michael', 'Krakowka, Steven', 'Li, Jianrong']",mBio,,,True
c99640294d5862d4482de51f9a442deaf09b53be,PMC,Identification of a Gamma Interferon-Activated Inhibitor of Translation-Like RNA Motif at the 3′ End of the Transmissible Gastroenteritis Coronavirus Genome Modulating Innate Immune Response,http://dx.doi.org/10.1128/mBio.00105-15,PMC4453530,25759500,CC BY-NC-SA,"A 32-nucleotide (nt) RNA motif located at the 3′ end of the transmissible gastroenteritis coronavirus (TGEV) genome was found to specifically interact with the host proteins glutamyl-prolyl-tRNA synthetase (EPRS) and arginyl-tRNA synthetase (RRS). This RNA motif has high homology in sequence and secondary structure with the gamma interferon-activated inhibitor of translation (GAIT) element, which is located at the 3′ end of several mRNAs encoding proinflammatory proteins. The GAIT element is involved in the translation silencing of these mRNAs through its interaction with the GAIT complex (EPRS, heterogeneous nuclear ribonucleoprotein Q, ribosomal protein L13a, and glyceraldehyde 3-phosphate dehydrogenase) to favor the resolution of inflammation. Interestingly, we showed that the viral RNA motif bound the GAIT complex and inhibited the in vitro translation of a chimeric mRNA containing this RNA motif. To our knowledge, this is the first GAIT-like motif described in a positive RNA virus. To test the functional role of the GAIT-like RNA motif during TGEV infection, a recombinant coronavirus harboring mutations in this motif was engineered and characterized. Mutations of the GAIT-like RNA motif did not affect virus growth in cell cultures. However, an exacerbated innate immune response, mediated by the melanoma differentiation-associated gene 5 (MDA5) pathway, was observed in cells infected with the mutant virus compared with the response observed in cells infected with the parental virus. Furthermore, the mutant virus was more sensitive to beta interferon than the parental virus. All together, these data strongly suggested that the viral GAIT-like RNA motif modulates the host innate immune response.",2015 Mar 10,"['Marquez-Jurado, Silvia', 'Nogales, Aitor', 'Zuñiga, Sonia', 'Enjuanes, Luis', 'Almazán, Fernando']",mBio,,,True
bad4f135cd64a02e182260e7c1e4d9b6f3941695,PMC,Comments on Fouchier’s Calculation of Risk and Elapsed Time for Escape of a Laboratory-Acquired Infection from His Laboratory,http://dx.doi.org/10.1128/mBio.00268-15,PMC4453553,25873376,CC BY-NC-SA,,2015 Apr 14,"Klotz, Lynn C.",mBio,,,True
dd969a7721176db21314930b62e62a37e902dae5,PMC,Heparan Sulfate-Dependent Enhancement of Henipavirus Infection,http://dx.doi.org/10.1128/mBio.02427-14,PMC4453572,25759505,CC BY-NC-SA,"Nipah virus and Hendra virus are emerging, highly pathogenic, zoonotic paramyxoviruses that belong to the genus Henipavirus. They infect humans as well as numerous mammalian species. Both viruses use ephrin-B2 and -B3 as cell entry receptors, and following initial entry into an organism, they are capable of rapid spread throughout the host. We have previously reported that Nipah virus can use another attachment receptor, different from its entry receptors, to bind to nonpermissive circulating leukocytes, thereby promoting viral dissemination within the host. Here, this attachment molecule was identified as heparan sulfate for both Nipah virus and Hendra virus. Cells devoid of heparan sulfate were not able to mediate henipavirus trans-infection and showed reduced permissivity to infection. Virus pseudotyped with Nipah virus glycoproteins bound heparan sulfate and heparin but no other glycosaminoglycans in a surface plasmon resonance assay. Furthermore, heparin was able to inhibit the interaction of the viruses with the heparan sulfate and to block cell-mediated trans-infection of henipaviruses. Moreover, heparin was shown to bind to ephrin-B3 and to restrain infection of permissive cells in vitro. Consequently, treatment with heparin devoid of anticoagulant activity improved the survival of Nipah virus-infected hamsters. Altogether, these results reveal heparan sulfate as a new attachment receptor for henipaviruses and as a potential therapeutic target for the development of novel approaches against these highly lethal infections.",2015 Mar 10,"['Mathieu, Cyrille', 'Dhondt, Kévin P.', 'Châlons, Marie', 'Mély, Stéphane', 'Raoul, Hervé', 'Negre, Didier', 'Cosset, François-Loïc', 'Gerlier, Denis', 'Vivès, Romain R.', 'Horvat, Branka']",mBio,,,True
30f5bfe5ca79c2e25e5dca95d8dfe473b780a51a,PMC,Exploration of New Sites in Adenovirus Hexon for Foreign Peptides Insertion,http://dx.doi.org/10.2174/1874357901509010001,PMC4460227,26069516,CC BY-NC,"Adenoviral vectors are now being explored as vaccine carriers to prevent infectious diseases in humans and animals. There are two strategies aimed at the expression of a vaccine antigen by adenoviral vectors. The first includes an insertion of the foreign gene expression cassette into the E1 region. The second strategy is antigen incorporation into the viral capsid proteins. To extend this methodology, we have searched for new sites at the human adenovirus serotype 5 major capsid protein hexon for a vaccine antigen insertion. To this end, we utilized sites in the hexon hypervariable region (HVR) 7, 8 and 9 to display a 15-mer peptide containing the main neutralizing epitope of porcine reproductive and respiratory syndrome virus. However, we could not rescue the viruses with the insertions of the peptide into HVR 8 and 9, consistent with the viruses being unable to tolerate insertions at these sites. In contrast, the virus with the insertion of the peptide in HVR 7 was viable - growing well in cell culture and the inserted peptide was exposed on the virion surface.",2015 May 29,"['Hansra, Satyender', 'Pujhari, Sujit', 'Zakhartchouk, Alexander N']",Open Virol J,,,True
8de34443c38db9422b06a2f583416660f1dca670,PMC,Cathepsin W Is Required for Escape of Influenza A Virus from Late Endosomes,http://dx.doi.org/10.1128/mBio.00297-15,PMC4462628,26060270,CC BY-NC-SA,"Human cathepsin W (CtsW) is a cysteine protease, which was identified in a genome-wide RNA interference (RNAi) screen to be required for influenza A virus (IAV) replication. In this study, we show that reducing the levels of expression of CtsW reduces viral titers for different subtypes of IAV, and we map the target step of CtsW requirement to viral entry. Using a set of small interfering RNAs (siRNAs) targeting CtsW, we demonstrate that knockdown of CtsW results in a decrease of IAV nucleoprotein accumulation in the nuclei of infected cells at 3 h postinfection. Assays specific for the individual stages of IAV entry further show that attachment, internalization, and early endosomal trafficking are not affected by CtsW knockdown. However, we detected impaired escape of viral particles from late endosomes in CtsW knockdown cells. Moreover, fusion analysis with a dual-labeled influenza virus revealed a significant reduction in fusion events, with no detectable impact on endosomal pH, suggesting that CtsW is required at the stage of viral fusion. The defect in IAV entry upon CtsW knockdown could be rescued by ectopic expression of wild-type CtsW but not by the expression of a catalytically inactive mutant of CtsW, suggesting that the proteolytic activity of CtsW is required for successful entry of IAV. Our results establish CtsW as an important host factor for entry of IAV into target cells and suggest that CtsW could be a promising target for the development of future antiviral drugs.",2015 Jun 9,"['Edinger, Thomas O.', 'Pohl, Marie O.', 'Yángüez, Emilio', 'Stertz, Silke']",mBio,,,True
07241235ee553a5b165ed19b2091101128eca805,PMC,Detection and characterisation of novel bocavirus (genus Bocaparvovirus) and gastroenteritis viruses from asymptomatic pigs in Ireland,http://dx.doi.org/10.3402/iee.v5.27270,PMC4462827,26065833,CC BY-NC,"BACKGROUND: Livestock animals have been the assumed source of several human epidemics in recent years, for example, influenza H1N1, rotavirus G8/G9, and MERS-CoV. Surveillance of novel viruses in animals is essential to evaluate the risk to human and animal health and to determine any economic impact, for example, failure to thrive. There is a paucity of data regarding detection and characterisation of gastroenteritis viruses, particularly novel viruses, in porcines in Ireland. Recently, a number of small novel porcine DNA viruses have emerged globally, for example, torque teno sus virus, porcine bocavirus, and parvoviruses 2 & 4, and little is known about the biology and potential pathogenicity of these viruses. Bocaparvovirus is a genetically distinct group of viruses which has been recently detected in humans and animals. METHODS: In this study, the presence of gastroenteritis viruses (rotavirus A, porcine circovirus, adenovirus, and porcine bocavirus) was investigated in a selection of archived faecal samples from asymptomatic piglets from a commercial farm in Ireland. A total of 104 specimens were pooled and screened using conventional molecular techniques (PCR and RT-PCR), a subset of specimens (n=44) were then examined individually. Viral diversity was then investigated using statistical and phylogenetic techniques. RESULTS: Initial screening showed a high prevalence of PBoV in this farm, with the formation of three distinct groups in phylogenetic analysis. Other viruses were also investigated in this study with the first report of PCV, PAdV and lineage I G5 RVA in Ireland. Some specimens contained >1 virus, with statistical analysis indicating a strong correlation for mixed infections of PBoV and PAdV on this farm. CONCLUSION: Investigating the diversity of circulating enteric viruses on Irish porcine farms is important to improve the prophylactic tools available and to facilitate the early detection of changes in circulating viruses.",2015 Jun 9,"['Gunn, Lynda', 'Collins, Patrick James', 'Fanning, Séamus', 'McKillen, John', 'Morgan, John', 'Staines, Anthony', ""O'Shea, Helen""]",Infect Ecol Epidemiol,,,True
737650f6ab6664da7582430d4b45ff9dd2e76866,PMC,In-service training for health professionals to improve care of seriously ill newborns and children in low-income countries,http://dx.doi.org/10.1002/14651858.CD007071.pub3,PMC4463987,25968066,CC BY-NC-ND,"BACKGROUND: A variety of in-service emergency care training courses are currently being promoted as a strategy to improve the quality of care provided to seriously ill newborns and children in low-income countries. Most courses have been developed in high-income countries. However, whether these courses improve the ability of health professionals to provide appropriate care in low-income countries remains unclear. This is the first update of the original review. OBJECTIVES: To assess the effects of in-service emergency care training on health professionals' treatment of seriously ill newborns and children in low-income countries. SEARCH METHODS: For this update, we searched the Cochrane Database of Systematic Reviews, part of The Cochrane Library (http://www.cochranelibrary.com); MEDLINE, Ovid SP; EMBASE, Ovid SP; the Cochrane Central Register of Controlled Trials (CENTRAL), part of The Cochrane Library (http://www.cochranelibrary.com) (including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register); Science Citation Index and Social Sciences Citation Index, Institute for Scientific Information (ISI) Web of Knowledge/Science and eight other databases. We performed database searches in February 2015. We also searched clinical trial registries, websites of relevant organisations and reference lists of related reviews. We applied no date, language or publication status restrictions when conducting the searches. SELECTION CRITERIA: Randomised trials, non-randomised trials, controlled before and after studies and interrupted-time-series studies that compared the effects of in-service emergency care training versus usual care were eligible for inclusion. We included only hospital-based studies and excluded community-based studies. Two review authors independently screened and selected studies for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed study risk of bias and confidence in effect estimates (certainty of evidence) for each outcome using GRADE (Grades of Recommendation, Assessment, Development and Evaluation). We described results and presented them in GRADE tables. MAIN RESULTS: We identified no new studies in this update. Two randomised trials (which were included in the original review) met the review eligibility criteria. In the first trial, newborn resuscitation training compared with usual care improved provider performance of appropriate resuscitation (trained 66% vs usual care 27%, risk ratio 2.45, 95% confidence interval (CI) 1.75 to 3.42; moderate certainty evidence) and reduced inappropriate resuscitation (trained mean 0.53 vs usual care 0.92, mean difference 0.40, 95% CI 0.13 to 0.66; moderate certainty evidence). Effect on neonatal mortality was inconclusive (trained 28% vs usual care 25%, risk ratio 0.77, 95% CI 0.40 to 1.48; N = 27 deaths; low certainty evidence). Findings from the second trial suggest that essential newborn care training compared with usual care probably slightly improves delivery room newborn care practices (assessment of breathing, preparedness for resuscitation) (moderate certainty evidence). AUTHORS' CONCLUSIONS: In-service neonatal emergency care courses probably improve health professionals' treatment of seriously ill babies in the short term. Further multi-centre randomised trials evaluating the effects of in-service emergency care training on long-term outcomes (health professional practice and patient outcomes) are needed. PLAIN LANGUAGE SUMMARY: In-service training for health professionals to improve care of seriously ill newborns and children in low-income countries WHAT QUESTION WAS THE REVIEW ASKING? This is the first update of the original Cochrane review, whose objective was to find out whether additional emergency care training programmes can improve the ability of health workers in poor countries to care for seriously ill newborns and children admitted to hospitals. Researchers at The Cochrane Collaboration searched for all studies that could answer this question and found two relevant studies. WHAT ARE THE KEY MESSAGES? The review authors suggest that giving health professionals in poor countries additional training in emergency care probably improves their ability to care for seriously ill newborns. We need additional high-quality studies, including studies in which health professionals are trained to care for seriously ill older children. BACKGROUND: TRAINING HEALTH PROFESSIONALS TO CARE FOR SERIOUSLY ILL BABIES AND CHILDREN: In poor countries, many babies and children with serious illnesses die even though they have been cared for in hospitals. One reason for this may be that health workers in these countries often are not properly trained to offer the care that these children need. In poor countries, children often become seriously ill because of conditions such as pneumonia, meningitis and diarrhoea, and may need emergency care. For newborn babies, the most common reason for emergency care is too little oxygen to the baby during birth. If this goes on for too long, the person delivering the baby has to help the baby breathe, and sometimes has to get the baby's heart rate back to normal. This is called neonatal resuscitation. Neonatal resuscitation is a skilled task, and the health worker needs proper training. As babies need to be resuscitated quickly, the health worker needs to know how to prepare for this before the baby is born. For instance, he or she needs to know how to prepare the room and proper equipment. Health workers in poor countries often do not have these skills, and these babies are likely to die. Babies can also be harmed if the health worker does not resuscitate the baby correctly. Several training programmes have been developed to teach health workers how to give emergency care to seriously ill babies and children. But most of these have been developed and tested in wealthy countries, and we don't know whether they would work in poor countries. WHAT HAPPENS WHEN HEALTH PROFESSIONALS IN POOR COUNTRIES ARE GIVEN EXTRA TRAINING? The review authors found two relevant studies. These studies compared the practices of health professionals who had been given extra training in the care of newborns with the practices of health professionals who did not receive extra training. In the first study, nurses at a maternity hospital in Kenya completed a one-day training course on how to resuscitate newborn babies. This course was adapted from the UK Resuscitation Council, and it included lectures and practical training. The study suggests that after these training courses: health professionals are probably more likely to resuscitate newborn babies correctly (moderate certainty of the evidence); and newborn babies may be less likely to die while being resuscitated (low certainty of the evidence). In the second study, doctors, nurses and midwives in five Sri Lankan hospitals were given a four-day training course on how to prepare for and provide care for newborns. This course was adapted from the World Health Organization (WHO) Training Modules on Essential Newborn Care and Breastfeeding, and included lectures, demonstrations, hands-on training and small group discussions. This study suggests that after these training courses: health professionals probably are more likely to be well prepared to resuscitate newborn babies (moderate certainty of the evidence). Unfortunately, the two studies followed up with health professionals for only two to three months after they received training. We therefore don't know if the benefits of the training courses lasted over time. The review authors found no studies that looked at the effects of training programmes on the care of older children. HOW UP-TO-DATE IS THIS REVIEW? Review authors searched for studies that had been published up to February 2015.",2015 May 13,"['Opiyo, Newton', 'English, Mike']",Cochrane Database Syst Rev,,,True
8977825a7fbaa1e4d672a361e7122b48785f93dd,PMC,"Antibody engineering for increased potency, breadth and half-life",http://dx.doi.org/10.1097/COH.0000000000000148,PMC4465343,25760931,CC BY-NC-ND,"PURPOSE OF REVIEW: This review highlights recent developments in HIV-1 antibody engineering and discusses the effects of increased polyreactivity on serum half-lives of engineered antibodies. RECENT FINDINGS: Recent studies have uncovered a wealth of information about the relationship between the sequences and efficacies of anti-HIV-1 antibodies through a combination of bioinformatics, structural characterization and in vivo studies. This knowledge has stimulated efforts to enhance antibody breadth and potency for therapeutic use. Although some engineered antibodies have shown increased polyreactivity and short half-lives, promising efforts are circumventing these problems. SUMMARY: Antibodies are desirable as therapeutics due to their ability to recognize targets with both specificity and high affinity. Furthermore, the ability of antibodies to stimulate Fc-mediated effector functions can increase their utility. Thus, mAbs have become central to strategies for the treatment of various diseases. Using both targeted and library-based approaches, antibodies can be engineered to improve their therapeutic properties. This article will discuss recent antibody engineering efforts to improve the breadth and potency of anti-HIV-1 antibodies. The polyreactivity of engineered HIV-1 bNAbs and the effect on serum half-life will be explored along with strategies to overcome problems introduced by engineering antibodies. Finally, advances in creating bispecific anti-HIV-1 reagents are discussed.",2015 May 15,"['Sievers, Stuart A.', 'Scharf, Louise', 'West, Anthony P.', 'Bjorkman, Pamela J.']",Curr Opin HIV AIDS,,,True
80228934cbb48467699deb5d9ea5826c635939a9,PMC,Danger of Potential-Pandemic-Pathogen Research Enterprises,http://dx.doi.org/10.1128/mBio.00815-15,PMC4471565,26081636,CC BY-NC-SA,,2015 Jun 16,"Klotz, Lynn C.",mBio,,,True
fc363739ad7ec8d796aba6af478d986a4c0f5f3f,PMC,Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms,http://dx.doi.org/10.5114/ceji.2015.50836,PMC4472542,26155186,CC BY-NC-ND,"In recent years, many studies have reported potential associations between cytokine gene polymorphisms and the development, course, and outcome of sepsis, often with apparently conflicting results. The objective of this study was to investigate single nucleotide polymorphism (SNP) in the interleukin (IL)-1β –31 T/C, IL-6 –174 G/C, tumor necrosis factor α (TNF-α) –308 G/A, and interferon γ (IFN-γ) +874 A/T genes for their possible association with susceptibility to early onset sepsis (EOS) in Saudi newborn infants. A total of 205 newborn infants aged 1-2 days were consecutively enrolled onto the study having met the inclusion criteria (as per the research protocol). DNA was extracted from filter papers using the Chelex-100 method. The cytokines SNP were genotyping using Taqman 5’ nuclease allelic discrimination. For cytokine measurements we used the commercially available Enzyme-Linked Immunosorbent Assay (ELISA) kit. Our results show that the circulating IL-1β, IL-6, TNF-α, and IFN-γ were significantly (p < 0.001) elevated in EOS patients compared to suspected and sepsis-free control groups; and IL-1β –31C, IL-6 –174G, TNF-α –308G, and IFN-γ +874A alleles were associated with EOS in Saudi infants. In conclusion, analysis of cytokines concentrations and SNP for the four tested genes can be used as a predictor of sepsis outcome in newborns.",2015 Apr 22,"['Allam, Gamal', 'Alsulaimani, Adnan A.', 'Alzaharani, Ali K.', 'Nasr, Amre']",Cent Eur J Immunol,,,True
6e4d9a7b61701ca9620df0205d89b7fb8c22f265,PMC,Treating the Host Response to Ebola Virus Disease with Generic Statins and Angiotensin Receptor Blockers,http://dx.doi.org/10.1128/mBio.00716-15,PMC4479704,26106080,CC BY-NC-SA,"Treatments targeting the Ebola virus may eventually be shown to work, but they will not have an impact on overall Ebola mortality in West Africa. Endothelial dysfunction is responsible for the fluid and electrolyte imbalances seen in Ebola patients. Because inexpensive generic statins and angiotensin receptor blockers restore endothelial barrier integrity, they can be used to treat the host response in these patients. In Sierra Leone, approximately 100 Ebola patients were treated with this combination, and reports indicate that survival was greatly improved.",2015 Jun 23,"['Fedson, David S.', 'Jacobson, Jeffrey R.', 'Rordam, Ole Martin', 'Opal, Steven M.']",mBio,,,True
a397f653ecd65b3cd26cf587207f2eec48b0e954,PMC,Better Understanding on MERS Corona Virus Outbreak in Korea,http://dx.doi.org/10.3346/jkms.2015.30.7.835,PMC4479933,26130942,CC BY-NC,,2015 Jul 10,"Lee, Jacob",J Korean Med Sci,,,True
096c2c85e046f4ebb34552e0a21bcd69907d1b81,PMC,Infectious disease screening among stem cell transplant donors: An Institutional experience in Saudi Arabia,http://dx.doi.org/10.5214/ans.0972.7531.220206,PMC4480260,26130912,CC BY-NC-ND,"BACKGROUND: Hematopoietic stem cell transplantation (HSCT) involves the infusion of hematopoietic stem cells from a suitable donor to a patient who has undergone chemotherapy. Stem Cell transplantation is used for the treatment for a wide variety of diseases, including leukemia and lymphoma. PURPOSE: This study highlights prevention strategies of infectious diseases among HSCT donors and recipients in our institute as guided by International guidelines. We aim to highlight the strategy for extensive screening of HIV, Hepatitis B and C, CMV infection and syphilis cases in all the stem cell units stored in our facility METHODS: We searched the institutional database to identify cases of infectious diseases among HSC transplants. Extensive donor evaluation was conducted through screening and laboratory infectious disease testing for HIV, Hepatitis B and C, CMV infection and syphilis. RESULTS: Between 1996 and 2014, 263 consecutive adult HSCT were performed. An approximate equal number of autologous and allogeneic HSC collections were undertaken. The median age for autologous donors was 35 years, whereas that of allogeneic donors is 25 years. Of the 263 stem cell donors, we found 18 patients (autologous) and 2 donors (allogeneic) to be infected. We did not find any of the donors infected with HIV by the serology as well as the NAT testing protocol CONCLUSION: Donor screening and testing is the most critical parameter in stem cell transplantation in order to ensure the safety of the product to be transplanted. Modifications in the regulations related to donor screening are aimed at providing safe transplantation and negate the risk of accidental infection of the donor.",2015 Apr,"['Alsuhaibani, Omar', 'Pereira, Winston Costa', 'Tareeqanwar, Mohammed', 'Khizzi, Nora El', 'Bakheswain, Saadia', 'Shaker, Amira', 'Elyamany, Ghaleb']",Ann Neurosci,,,True
64026e37a33880c07a23deabc68e8e0d8d790c59,PMC,How urbanization affects the epidemiology of emerging infectious diseases,http://dx.doi.org/10.3402/iee.v5.27060,PMC4481042,26112265,CC BY-NC,"The world is becoming more urban every day, and the process has been ongoing since the industrial revolution in the 18th century. The United Nations now estimates that 3.9 billion people live in urban centres. The rapid influx of residents is however not universal and the developed countries are already urban, but the big rise in urban population in the next 30 years is expected to be in Asia and Africa. Urbanization leads to many challenges for global health and the epidemiology of infectious diseases. New megacities can be incubators for new epidemics, and zoonotic diseases can spread in a more rapid manner and become worldwide threats. Adequate city planning and surveillance can be powerful tools to improve the global health and decrease the burden of communicable diseases.",2015 Jun 24,"Neiderud, Carl-Johan",Infect Ecol Epidemiol,,,True
7a0d4f63df57cc9873f41c16e27b5ec3d2b76f88,PMC,Deep sequencing analysis of viral infection and evolution allows rapid and detailed characterization of viral mutant spectrum,http://dx.doi.org/10.1093/bioinformatics/btv101,PMC4481840,25701575,CC BY-NC,"Motivation: The study of RNA virus populations is a challenging task. Each population of RNA virus is composed of a collection of different, yet related genomes often referred to as mutant spectra or quasispecies. Virologists using deep sequencing technologies face major obstacles when studying virus population dynamics, both experimentally and in natural settings due to the relatively high error rates of these technologies and the lack of high performance pipelines. In order to overcome these hurdles we developed a computational pipeline, termed ViVan (Viral Variance Analysis). ViVan is a complete pipeline facilitating the identification, characterization and comparison of sequence variance in deep sequenced virus populations. Results: Applying ViVan on deep sequenced data obtained from samples that were previously characterized by more classical approaches, we uncovered novel and potentially crucial aspects of virus populations. With our experimental work, we illustrate how ViVan can be used for studies ranging from the more practical, detection of resistant mutations and effects of antiviral treatments, to the more theoretical temporal characterization of the population in evolutionary studies. Availability and implementation: Freely available on the web at http://www.vivanbioinfo.org Contact: nshomron@post.tau.ac.il Supplementary information: Supplementary data are available at Bioinformatics online.",2015 Jul 1,"['Isakov, Ofer', 'Bordería, Antonio V.', 'Golan, David', 'Hamenahem, Amir', 'Celniker, Gershon', 'Yoffe, Liron', 'Blanc, Hervé', 'Vignuzzi, Marco', 'Shomron, Noam']",Bioinformatics,,,True
c7bfc28694d26da69c71759b8981101d15f38420,PMC,A clear 'wake-up call' from Korea,http://dx.doi.org/10.5051/jpis.2015.45.3.81,PMC4485063,26131367,CC BY-NC,,2015 Jun 24,"Kim, Tae-Il",J Periodontal Implant Sci,,,False
b19635e3a0906506d07c05a4dc8ecd8f76f7e077,PMC,13th ERS Lung Science Conference. The most important take home messages: News from the Underground,http://dx.doi.org/10.1183/20734735.04015,PMC4487375,26306116,CC BY-NC,"The 13th ERS Lung Science Conference (LSC) was organised to bring academics together from all over the world to present and discuss the latest developments regarding lung infection and immunity. The conference took place in breathtaking Estoril, Portugal; however, it wasn’t the beautiful surroundings that were our main motivation to attend, but instead the scientific merit of the conference and the chance to create new scientific collaborations. The scientific programme [1] was packed with the most up-to-date content in the field of lung infection and immunity and included some of the top researchers within this exciting area. Moreover, the convenient size of the LSC offered the opportunity to renew and intensify friendships and collaborations. In particular, for researchers at the start of their career, this is a great feature and we therefore warmly recommend the LSC to ERS Juniors Members!",2015 Jun,"['Bikov, Andras', 'Boots, Agnes', 'Bjerg, Anders', 'Jacinto, Tiago', 'Olland, Anne', 'Skoczyński, Szymon']",Breathe (Sheff),,,True
5da2c99de592512c4295cc5c1b941e5f6548f065,PMC,One cannot rule them all: Are bacterial toxins-antitoxins druggable?,http://dx.doi.org/10.1093/femsre/fuv002,PMC4487406,25796610,CC BY-NC,"Type II (proteic) toxin–antitoxin (TA) operons are widely spread in bacteria and archaea. They are organized as operons in which, usually, the antitoxin gene precedes the cognate toxin gene. The antitoxin generally acts as a transcriptional self-repressor, whereas the toxin acts as a co-repressor, both proteins constituting a harmless complex. When bacteria encounter a stressful environment, TAs are triggered. The antitoxin protein is unstable and will be degraded by host proteases, releasing the free toxin to halt essential processes. The result is a cessation of cell growth or even death. Because of their ubiquity and the essential processes targeted, TAs have been proposed as good candidates for development of novel antimicrobials. We discuss here the possible druggability of TAs as antivirals and antibacterials, with focus on the potentials and the challenges that their use may find in the ‘real’ world. We present strategies to develop TAs as antibacterials in view of novel technologies, such as the use of very small molecules (fragments) as inhibitors of protein–protein interactions. Appropriate fragments could disrupt the T:A interfaces leading to the release of the targeted TA pair. Possible ways of delivery and formulation of Tas are also discussed.",2015 Jul 21,"['Chan, Wai Ting', 'Balsa, Dolors', 'Espinosa, Manuel']",FEMS Microbiol Rev,,,True
aec2e91fcbfb520fd6c2996efe20c6f42afc9a69,PMC,Herbal drug BNO 1016 is safe and effective in the treatment of acute viral rhinosinusitis,http://dx.doi.org/10.3109/00016489.2014.952047,PMC4487568,25496178,CC BY-NC-ND,"Conclusion: Daily intake of 480 mg of BNO 1016 for 15 days is an effective treatment in acute viral rhinosinusitis. Objectives: The pooled efficacy data of two similar randomized placebo-controlled clinical trials were analyzed. Safety was evaluated on the basis of the individual trials. Methods: The efficacy analysis was based on 589 patients. Treatment was performed orally with either 3 × 160 mg BNO 1016 (n = 294) or 3 × placebo (n = 295) for 15 days. In both trials patients underwent five visits to the investigational sites. Symptoms were evaluated according to the EPOS 2012 guideline. Ultrasonography was used to confirm the diagnosis at onset of treatment and the remission of symptoms at the last visit. Efficacy was evaluated by the investigator as the mean major symptom score (MSS) at the end of treatment (visit 5, day 14). Patients reported symptoms and social/emotional consequences of rhinosinusitis using a quality of life questionnaire (SNOT-20 GAV). Results: MSS improved during the treatment period by a mean of 10.02 ± 1.61 score points to 2.47 ± 2.55 for BNO 1016 and of 9.87 ± 1.52 to 3.63 ± 3.63 for placebo. Differences between treatment groups at end of therapy (1.16 ± 3.14 score points; p < 0.0001) and patient-assessed quality of life (p = 0.0015) were statistically significant in favor of BNO 1016.",2015 Jan 2,"['Jund, Rainer', 'Mondigler, Martin', 'Stammer, Holger', 'Stierna, Pontus', 'Bachert, Claus']",Acta Otolaryngol,,,True
0a296d80d8a8c0408c1ea9559c0f0589fb35cb03,PMC,Molecular epidemiology and phylogenetic analysis of diverse bovine astroviruses associated with diarrhea in cattle and water buffalo calves in China,http://dx.doi.org/10.1292/jvms.14-0252,PMC4488400,25716289,CC BY-NC-ND,"Astroviruses are the principal causative agents of gastroenteritis in humans and have been associated with diarrhea in other mammals as well as birds. However, astroviral infection of animals had been poorly studied. In the present study, 211 rectal swabs collected from cattle and water buffalo calves with mild to severe diarrhea were tested for bovine astrovirus (BAstV) by RT-PCR. Results: 92/211 (43.6%) samples were positive for BAstV, at a rate of 46.10% (71/154) in cattle and 36.84% (21/57) in water buffalo. Phylogenetic analysis based on the partial and full-length of 25 ORF2 amino acid sequences obtained in this study classified the Guangxi BAstVs isolates into five subgroups under the genus of Mamastrovirus, genotype MAstV33, which suggested that the water buffalo was a new host of this genogroup that previously included only cattle and roe deer. Despite the origin of the host, the Guangxi BAstV isolates were closely related to the BAstV Hong Kong isolates (B18/HK and B76-2/HK), but highly divergent from the BAstV NeuroS1 isolate previously associated with neurologic disease in cattle in the U.S.A. Nucleotide sequence-based characterization of the ORF1b/ORF2 junction and corresponding overlapping regions showed distinctive properties, which may be common to BAstVs. Our results suggested that cattle and water buffalo are prone to infection of closely related astroviruses, which probably evolved from the same ancestor. The current study described astroviruses in water buffalo for the first time and is thus far among the largest epidemiological investigations of BAstV infection in cattle conducted in China.",2015 Jun 13,"['ALFRED, Niyokwishimira', 'LIU, Huan', 'LI, Mu Lan', 'HONG, Shao Feng', 'TANG, Hai Bo', 'WEI, Zu Zhang', 'CHEN, Ying', 'LI, Fa Kai', 'ZHONG, Yi Zhi', 'HUANG, Wei Jian']",J Vet Med Sci,,,True
17bfdf17f46ae63e52c3e7c085bac97057e9ae61,PMC,NS5A Domain 1 and Polyprotein Cleavage Kinetics Are Critical for Induction of Double-Membrane Vesicles Associated with Hepatitis C Virus Replication,http://dx.doi.org/10.1128/mBio.00759-15,PMC4488949,26152585,CC BY-NC-SA,"Induction of membrane rearrangements in the cytoplasm of infected cells is a hallmark of positive-strand RNA viruses. These altered membranes serve as scaffolds for the assembly of viral replication factories (RFs). We have recently shown that hepatitis C virus (HCV) infection induces endoplasmic reticulum-derived double-membrane vesicles (DMVs) representing the major constituent of the RF within the infected cell. RF formation requires the concerted action of nonstructural action of nonstructural protein (NS)3, -4A, protein (NS)3 -4A, -4B, -5A, and -5B. Although the sole expression of NS5A is sufficient to induce DMV formation, its efficiency is very low. In this study, we dissected the determinants within NS5A responsible for DMV formation and found that RNA-binding domain 1 (D1) and the amino-terminal membrane anchor are indispensable for this process. In contrast, deletion of NS5A D2 or D3 did not affect DMV formation but disrupted RNA replication and virus assembly, respectively. To identify cis- and trans-acting factors of DMV formation, we established a trans cleavage assay. We found that induction of DMVs requires full-length NS3, whereas a helicase-lacking mutant was unable to trigger DMV formation in spite of efficient polyprotein cleavage. Importantly, a mutation accelerating cleavage kinetics at the NS4B-5A site diminished DMV formation, while the insertion of an internal ribosome entry site mimicking constitutive cleavage at this boundary completely abolished this process. These results identify key determinants governing the biogenesis of the HCV RF with possible implications for our understanding of how RFs are formed in other positive-strand RNA viruses.",2015 Jul 7,"['Romero-Brey, Inés', 'Berger, Carola', 'Kallis, Stephanie', 'Kolovou, Androniki', 'Paul, David', 'Lohmann, Volker', 'Bartenschlager, Ralf']",mBio,,,True
462b5690d40bb449810209b2b893b078d65a0d47,PMC,Science and technology - human society convergence plan to solve social problems - the new virus explained,http://dx.doi.org/10.12965/jer.150214,PMC4492419,26171375,CC BY-NC,,2015 Jun 30,"Kim, Khae-Hawn",J Exerc Rehabil,,,False
a6637a61fc42c734211f7df5089e88f859d0da5a,PMC,In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures,http://dx.doi.org/10.1038/cr.2015.50,PMC4493273,25916549,CC BY-NC-ND,"Epstein-Barr virus (EBV) can infect both susceptible B lymphocytes and non-susceptible epithelial cells (ECs). Viral tropism analyses have revealed two intriguing means of EBV infection, either by a receptor-mediated infection of B cells or by a cell-to-cell contact-mediated infection of non-susceptible ECs. Herein, we report a novel “in-cell infection” mechanism for EBV infection of non-susceptible ECs through the formation of cell-in-cell structures. Epithelial CNE-2 cells were invaded by EBV-infected Akata B cells to form cell-in-cell structures in vitro. Such unique cellular structures could be readily observed in the specimens of nasopharyngeal carcinoma. Importantly, the formation of cell-in-cell structures led to the autonomous activation of EBV within Akata cells and subsequent viral transmission to CNE-2 cells, as evidenced by the expression of viral genes and the presence of virion particles in CNE-2 cells. Significantly, EBV generated from in-cell infected ECs displayed altered tropism with higher infection efficacy to both B cells and ECs. In addition to CNE-2 tumor cells, cell-in-cell structure formation could also mediate EBV infection of NPEC1-Bmi1 cells, an immortalized nasopharyngeal epithelial cell line. Furthermore, efficient infection by this mechanism involved the activation of the PI3K/AKT signaling pathway. Thus, our study identified “in-cell infection” as a novel mechanism for EBV infection. Given the diversity of virus-infected cells and the prevalence of cell-in-cell structures during chronic infection, we speculate that “in-cell infection” is likely a general mechanism for EBV and other viruses to infect non-susceptible ECs.",2015 Jul 28,"['Ni, Chao', 'Chen, Yuhui', 'Zeng, Musheng', 'Pei, Rongjuan', 'Du, Yong', 'Tang, Linquan', 'Wang, Mengyi', 'Hu, Yazhuo', 'Zhu, Hanyu', 'He, Meifang', 'Wei, Xiawei', 'Wang, Shan', 'Ning, Xiangkai', 'Wang, Manna', 'Wang, Jufang', 'Ma, Li', 'Chen, Xinwen', 'Sun, Qiang', 'Tang, Hong', 'Wang, Ying', 'Wang, Xiaoning']",Cell Res,,,True
4c5bfd87ae4853adcf4dfc79431ddb2fed47f24a,PMC,In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures,http://dx.doi.org/10.1038/cr.2015.50,PMC4493273,25916549,CC BY-NC-ND,"Epstein-Barr virus (EBV) can infect both susceptible B lymphocytes and non-susceptible epithelial cells (ECs). Viral tropism analyses have revealed two intriguing means of EBV infection, either by a receptor-mediated infection of B cells or by a cell-to-cell contact-mediated infection of non-susceptible ECs. Herein, we report a novel “in-cell infection” mechanism for EBV infection of non-susceptible ECs through the formation of cell-in-cell structures. Epithelial CNE-2 cells were invaded by EBV-infected Akata B cells to form cell-in-cell structures in vitro. Such unique cellular structures could be readily observed in the specimens of nasopharyngeal carcinoma. Importantly, the formation of cell-in-cell structures led to the autonomous activation of EBV within Akata cells and subsequent viral transmission to CNE-2 cells, as evidenced by the expression of viral genes and the presence of virion particles in CNE-2 cells. Significantly, EBV generated from in-cell infected ECs displayed altered tropism with higher infection efficacy to both B cells and ECs. In addition to CNE-2 tumor cells, cell-in-cell structure formation could also mediate EBV infection of NPEC1-Bmi1 cells, an immortalized nasopharyngeal epithelial cell line. Furthermore, efficient infection by this mechanism involved the activation of the PI3K/AKT signaling pathway. Thus, our study identified “in-cell infection” as a novel mechanism for EBV infection. Given the diversity of virus-infected cells and the prevalence of cell-in-cell structures during chronic infection, we speculate that “in-cell infection” is likely a general mechanism for EBV and other viruses to infect non-susceptible ECs.",2015 Jul 28,"['Ni, Chao', 'Chen, Yuhui', 'Zeng, Musheng', 'Pei, Rongjuan', 'Du, Yong', 'Tang, Linquan', 'Wang, Mengyi', 'Hu, Yazhuo', 'Zhu, Hanyu', 'He, Meifang', 'Wei, Xiawei', 'Wang, Shan', 'Ning, Xiangkai', 'Wang, Manna', 'Wang, Jufang', 'Ma, Li', 'Chen, Xinwen', 'Sun, Qiang', 'Tang, Hong', 'Wang, Ying', 'Wang, Xiaoning']",Cell Res,,,False
670afb0841beffcf0b97fc0a0bfd70d16dd627e9,PMC,In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures,http://dx.doi.org/10.1038/cr.2015.50,PMC4493273,25916549,CC BY-NC-ND,"Epstein-Barr virus (EBV) can infect both susceptible B lymphocytes and non-susceptible epithelial cells (ECs). Viral tropism analyses have revealed two intriguing means of EBV infection, either by a receptor-mediated infection of B cells or by a cell-to-cell contact-mediated infection of non-susceptible ECs. Herein, we report a novel “in-cell infection” mechanism for EBV infection of non-susceptible ECs through the formation of cell-in-cell structures. Epithelial CNE-2 cells were invaded by EBV-infected Akata B cells to form cell-in-cell structures in vitro. Such unique cellular structures could be readily observed in the specimens of nasopharyngeal carcinoma. Importantly, the formation of cell-in-cell structures led to the autonomous activation of EBV within Akata cells and subsequent viral transmission to CNE-2 cells, as evidenced by the expression of viral genes and the presence of virion particles in CNE-2 cells. Significantly, EBV generated from in-cell infected ECs displayed altered tropism with higher infection efficacy to both B cells and ECs. In addition to CNE-2 tumor cells, cell-in-cell structure formation could also mediate EBV infection of NPEC1-Bmi1 cells, an immortalized nasopharyngeal epithelial cell line. Furthermore, efficient infection by this mechanism involved the activation of the PI3K/AKT signaling pathway. Thus, our study identified “in-cell infection” as a novel mechanism for EBV infection. Given the diversity of virus-infected cells and the prevalence of cell-in-cell structures during chronic infection, we speculate that “in-cell infection” is likely a general mechanism for EBV and other viruses to infect non-susceptible ECs.",2015 Jul 28,"['Ni, Chao', 'Chen, Yuhui', 'Zeng, Musheng', 'Pei, Rongjuan', 'Du, Yong', 'Tang, Linquan', 'Wang, Mengyi', 'Hu, Yazhuo', 'Zhu, Hanyu', 'He, Meifang', 'Wei, Xiawei', 'Wang, Shan', 'Ning, Xiangkai', 'Wang, Manna', 'Wang, Jufang', 'Ma, Li', 'Chen, Xinwen', 'Sun, Qiang', 'Tang, Hong', 'Wang, Ying', 'Wang, Xiaoning']",Cell Res,,,False
45ea187594187eda7fb90b30d5462bda16826ff8,PMC,In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures,http://dx.doi.org/10.1038/cr.2015.50,PMC4493273,25916549,CC BY-NC-ND,"Epstein-Barr virus (EBV) can infect both susceptible B lymphocytes and non-susceptible epithelial cells (ECs). Viral tropism analyses have revealed two intriguing means of EBV infection, either by a receptor-mediated infection of B cells or by a cell-to-cell contact-mediated infection of non-susceptible ECs. Herein, we report a novel “in-cell infection” mechanism for EBV infection of non-susceptible ECs through the formation of cell-in-cell structures. Epithelial CNE-2 cells were invaded by EBV-infected Akata B cells to form cell-in-cell structures in vitro. Such unique cellular structures could be readily observed in the specimens of nasopharyngeal carcinoma. Importantly, the formation of cell-in-cell structures led to the autonomous activation of EBV within Akata cells and subsequent viral transmission to CNE-2 cells, as evidenced by the expression of viral genes and the presence of virion particles in CNE-2 cells. Significantly, EBV generated from in-cell infected ECs displayed altered tropism with higher infection efficacy to both B cells and ECs. In addition to CNE-2 tumor cells, cell-in-cell structure formation could also mediate EBV infection of NPEC1-Bmi1 cells, an immortalized nasopharyngeal epithelial cell line. Furthermore, efficient infection by this mechanism involved the activation of the PI3K/AKT signaling pathway. Thus, our study identified “in-cell infection” as a novel mechanism for EBV infection. Given the diversity of virus-infected cells and the prevalence of cell-in-cell structures during chronic infection, we speculate that “in-cell infection” is likely a general mechanism for EBV and other viruses to infect non-susceptible ECs.",2015 Jul 28,"['Ni, Chao', 'Chen, Yuhui', 'Zeng, Musheng', 'Pei, Rongjuan', 'Du, Yong', 'Tang, Linquan', 'Wang, Mengyi', 'Hu, Yazhuo', 'Zhu, Hanyu', 'He, Meifang', 'Wei, Xiawei', 'Wang, Shan', 'Ning, Xiangkai', 'Wang, Manna', 'Wang, Jufang', 'Ma, Li', 'Chen, Xinwen', 'Sun, Qiang', 'Tang, Hong', 'Wang, Ying', 'Wang, Xiaoning']",Cell Res,,,False
f94e031dce4a39f707e03ac6b151a6d68a8a0e61,PMC,In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures,http://dx.doi.org/10.1038/cr.2015.50,PMC4493273,25916549,CC BY-NC-ND,"Epstein-Barr virus (EBV) can infect both susceptible B lymphocytes and non-susceptible epithelial cells (ECs). Viral tropism analyses have revealed two intriguing means of EBV infection, either by a receptor-mediated infection of B cells or by a cell-to-cell contact-mediated infection of non-susceptible ECs. Herein, we report a novel “in-cell infection” mechanism for EBV infection of non-susceptible ECs through the formation of cell-in-cell structures. Epithelial CNE-2 cells were invaded by EBV-infected Akata B cells to form cell-in-cell structures in vitro. Such unique cellular structures could be readily observed in the specimens of nasopharyngeal carcinoma. Importantly, the formation of cell-in-cell structures led to the autonomous activation of EBV within Akata cells and subsequent viral transmission to CNE-2 cells, as evidenced by the expression of viral genes and the presence of virion particles in CNE-2 cells. Significantly, EBV generated from in-cell infected ECs displayed altered tropism with higher infection efficacy to both B cells and ECs. In addition to CNE-2 tumor cells, cell-in-cell structure formation could also mediate EBV infection of NPEC1-Bmi1 cells, an immortalized nasopharyngeal epithelial cell line. Furthermore, efficient infection by this mechanism involved the activation of the PI3K/AKT signaling pathway. Thus, our study identified “in-cell infection” as a novel mechanism for EBV infection. Given the diversity of virus-infected cells and the prevalence of cell-in-cell structures during chronic infection, we speculate that “in-cell infection” is likely a general mechanism for EBV and other viruses to infect non-susceptible ECs.",2015 Jul 28,"['Ni, Chao', 'Chen, Yuhui', 'Zeng, Musheng', 'Pei, Rongjuan', 'Du, Yong', 'Tang, Linquan', 'Wang, Mengyi', 'Hu, Yazhuo', 'Zhu, Hanyu', 'He, Meifang', 'Wei, Xiawei', 'Wang, Shan', 'Ning, Xiangkai', 'Wang, Manna', 'Wang, Jufang', 'Ma, Li', 'Chen, Xinwen', 'Sun, Qiang', 'Tang, Hong', 'Wang, Ying', 'Wang, Xiaoning']",Cell Res,,,False
dd0d61765564577b04e2b012930936fcb7b3f7fc,PMC,"An Unexpected Outbreak of Middle East Respiratory Syndrome Coronavirus Infection in the Republic of Korea, 2015",http://dx.doi.org/10.3947/ic.2015.47.2.120,PMC4495271,26157591,CC BY-NC,"This report includes a summary of a current outbreak of the Middle East Respiratory Syndrome Coronavirus infection in the Republic of Korea as of June 23, 2015. Epidemiologic, clinical, and laboratory investigations of this outbreak are ongoing.",2015 Jun 30,"[None, None]",Infect Chemother,,,True
82994e41869e2ada2685ca424ac757c20e6c88c3,PMC,A Case of Statin-Induced Interstitial Pneumonitis due to Rosuvastatin,http://dx.doi.org/10.4046/trd.2015.78.3.281,PMC4499600,26175786,CC BY-NC,"Statins lower the hyperlipidemia and reduce the incidence of cardiovascular events and related mortality. A 60-year-old man who was diagnosed with a transient ischemic attack was started on acetyl-L-carnitine, cilostazol, and rosuvastatin. After rosuvastatin treatment for 4 weeks, the patient presented with sudden onset fever, cough, and dyspnea. His symptoms were aggravated despite empirical antibiotic treatment. All infectious pathogens were excluded based on results of culture and polymerase chain reaction of the bronchoscopic wash specimens. Chest radiography showed diffuse ground-glass opacities in both lungs, along with several subpleural ground-glass opacity nodules; and a foamy alveolar macrophage appearance was confirmed on bronchoalveolar lavage. We suspected rosuvastatin-induced lung injury, discontinued rosuvastatin and initiated prednisolone 1 mg/kg tapered over 2weeks. After initiating steroid therapy, his symptoms and radiologic findings significantly improved. We suggest that clinicians should be aware of the potential for rosuvastatin-induced lung injury.",2015 Jul 30,"['Kim, Se Yong', 'Kim, Se Jin', 'Yoon, Doran', 'Hong, Seung Wook', 'Park, Sehhoon', 'Ock, Chan-Young']",Tuberc Respir Dis (Seoul),,,True
82f9d88193226177c20342d42a29a26ebba90fa1,PMC,"High proportion of MERS-CoV shedding dromedaries at slaughterhouse with a potential epidemiological link to human cases, Qatar 2014",http://dx.doi.org/10.3402/iee.v5.28305,PMC4505336,26183160,CC BY-NC,"Two of the earliest Middle East respiratory syndrome (MERS) cases were men who had visited the Doha central animal market and adjoining slaughterhouse in Qatar. We show that a high proportion of camels presenting for slaughter in Qatar show evidence for nasal MERS-CoV shedding (62/105). Sequence analysis showed the circulation of at least five different virus strains at these premises, suggesting that this location is a driver of MERS-CoV circulation and a high-risk area for human exposure. No correlation between RNA loads and levels of neutralizing antibodies was observed, suggesting limited immune protection and potential for reinfection despite previous exposure.",2015 Jul 15,"['Farag, Elmoubasher A. B. A.', 'Reusken, Chantal B. E. M.', 'Haagmans, Bart L.', 'Mohran, Khaled A.', 'Raj, V. Stalin', 'Pas, Suzan D.', 'Voermans, Jolanda', 'Smits, Saskia L.', 'Godeke, Gert-Jan', 'Al-Hajri, Mohd. M.', 'Alhajri, Farhoud H.', 'Al-Romaihi, Hamad E.', 'Ghobashy, Hazem', 'El-Maghraby, Mamdouh M.', 'El-Sayed, Ahmed M.', 'Al Thani, Mohamed H. J.', 'Al-Marri, Salih', 'Koopmans, Marion P. G.']",Infect Ecol Epidemiol,,,True
314f4b76581376bc7b40e69a9f0bc9153298cb8e,PMC,"Evaluation of REDCap as a Tool for Outbreak Data Management, Illinois, 2013-2014",http://dx.doi.org/10.5210/ojphi.v7i1.5836,PMC4512356,,CC BY-NC,,2015 Feb 26,"['Vahora, Jennifer', 'Arwady, M. Allison']",Online J Public Health Inform,,,True
524738e8e638c805f7c00ccbafb2821e8cbae115,PMC,2014 International Society for Disease Surveillance Conference Translating Research and Surveillance into Action,http://dx.doi.org/10.5210/ojphi.v7i1.5655,PMC4512412,,CC BY-NC,,2015 Feb 26,"['Painter, Ian', 'Lojo, José']",Online J Public Health Inform,,,False
1bcbb56b7ec449ef48d930dce2f02fdc10aeb3e7,PMC,Response of the National Biosurveillance Integration Center to the Emergence of Porcine Epidemic Diarrhea Virus in the United States,http://dx.doi.org/10.5210/ojphi.v7i1.5777,PMC4512424,,CC BY-NC,,2015 Feb 26,"['Brown, Yandace K.', 'Blessington, Tyann']",Online J Public Health Inform,,,False
562482615b134bd07325e607832d9d67aaa13e60,PMC,Use of Syndromic Data for Enhanced Surveillance: MERS Like-Syndrome,http://dx.doi.org/10.5210/ojphi.v7i1.5735,PMC4512432,,CC BY-NC,,2015 Feb 26,"['Dey, Achintya N.', 'Miller, Matthew', 'Coletta, Michael', 'Ajani, Umed']",Online J Public Health Inform,,,False
7d6e1512b86e2006936b67f5a39f117330e2c98e,PMC,Overcoming Operational Differences to Attain a National Picture for Novel Threats,http://dx.doi.org/10.5210/ojphi.v7i1.5678,PMC4512434,,CC BY-NC,,2015 Feb 26,"['Coletta, Michael', 'Dey, Achintya N.', 'Miller, Matthew', 'Hicks, Peter', 'Ajani, Umed']",Online J Public Health Inform,,,False
c6e43ac8c7b2d8529078ad2645c39814b52d5015,PMC,"Ebola, Enterovirus, MERS, Novel Flu, and other Challenges for Public Health Surveillance Practitioners",http://dx.doi.org/10.5210/ojphi.v7i1.5718,PMC4512435,,CC BY-NC,,2015 Feb 26,"['Siniscalchi, Alan', 'Evans, Brooke']",Online J Public Health Inform,,,True
71a02ec5050593d346595f2af85aa3ce3b403bdc,PMC,Assessing and Managing the Risks of Potential Pandemic Pathogen Research,http://dx.doi.org/10.1128/mBio.01075-15,PMC4513083,26199335,CC BY-NC-SA,,2015 Jul 21,"Rozell, Daniel J.",mBio,,,True
05248494136966d79614f475f8e5bb0880a20bf7,PMC,An Appropriate Lower Respiratory Tract Specimen Is Essential for Diagnosis of Middle East Respiratory Syndrome (MERS),http://dx.doi.org/10.3346/jkms.2015.30.8.1207,PMC4520955,26240502,CC BY-NC,,2015 Aug 15,"['Lee, Jae Hoon', 'Lee, Chang-Seop', 'Lee, Heung-Bum']",J Korean Med Sci,,,True
bbb6637a5feacde7301d594e1e1f96b339496c20,PMC,MERS Countermeasures as One of Global Health Security Agenda,http://dx.doi.org/10.3346/jkms.2015.30.8.997,PMC4520957,26240473,CC BY-NC,,2015 Aug 15,"Lee, Jong-Koo",J Korean Med Sci,,,True
4776a30b2dc8da97b0c419d7577dd959231bbd61,PMC,Cardiac Function in Kawasaki Disease Patients with Respiratory Symptoms,http://dx.doi.org/10.4070/kcj.2015.45.4.317,PMC4521110,26240586,CC BY-NC,"BACKGROUND AND OBJECTIVES: Respiratory symptoms are often observed in children with Kawasaki disease (KD) during the acute phase. The association of respiratory viruses in children with KD was investigated using multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) and tissue Doppler echocardiography. SUBJECTS AND METHODS: 138 KD patients were included from January 2010 to June 2013. We compared 3 groups (group 1: n=94, KD without respiratory symptoms; group 2: n=44, KD with respiratory symptoms; and group 3: n=50, febrile patients with respiratory symptoms). Laboratory data were obtained from each patient including N-terminal pro-brain natriuretic peptide (NT-proBNP). Echocardiographic measurements were compared between group 1 and group 2. RT-PCR was performed using nasopharyngeal secretion to screen for the presence of 14 viruses in groups 2 and 3. RESULTS: The incidence of KD with respiratory symptoms was 31.8%. The duration of fever was significantly longer, and coronary artery diameter was larger in group 2 than in group 1. Tei index was significantly higher and coronary artery diameter larger in group 2 than group 1. Coronary artery diameter, C-reactive protein levels, platelet count, alanine aminotransferase levels, and NT-pro BNP levels were significantly higher and albumin levels lower in group 2 compared with group 3. CONCLUSION: NT-pro BNP was a valuable diagnostic tool in differentiating KD from other febrile viral respiratory infections. Some viruses were more frequently observed in KD patients than in febrile controls. Tei index using tissue Doppler imaging was increased in KD patients with respiratory symptoms.",2015 Jul 16,"['Lee, Seul Bee', 'Choi, Han Seul', 'Son, Sejung', 'Hong, Young Mi']",Korean Circ J,,,True
7ed89e5691a56b6757c21984c3bbb733b5a2dfdc,PMC,Porcine epidemic diarrhea: a review of current epidemiology and available vaccines,http://dx.doi.org/10.7774/cevr.2015.4.2.166,PMC4524901,26273575,CC BY-NC,"Porcine epidemic diarrhea virus (PEDV), an Alphacoronavirus in the family Coronaviridae, causes acute diarrhea, vomiting, dehydration, and high mortality rates in neonatal piglets. PEDV can also cause diarrhea, agalactia, and abnormal reproductive cycles in pregnant sows. Although PEDV was first identified in Europe, it has resulted in significant economic losses in many Asian swine-raising countries, including Korea, China, Japan, Vietnam, and the Philippines. However, from April 2013 to the present, major outbreaks of PEDV have been reported in the United States, Canada, and Mexico. Moreover, intercontinental transmission of PEDV has increased mortality rates in seronegative neonatal piglets, resulting in 10% loss of the US pig population. The emergence and re-emergence of PEDV indicates that the virus is able to evade current vaccine strategies. Continuous emergence of multiple mutant strains from several regions has aggravated porcine epidemic diarrhea endemic conditions and highlighted the need for new vaccines based on the current circulating PEDV. Epidemic PEDV strains tend to be more pathogenic and cause increased death in pigs, thereby causing substantial financial losses for swine producers. In this review, we described the epidemiology of PEDV in several countries and present molecular characterization of current strains. We also discuss PEDV vaccines and related issues.",2015 Jul 29,"['Song, Daesub', 'Moon, Hyoungjoon', 'Kang, Bokyu']",Clin Exp Vaccine Res,,,True
6bb631f4a1c7c8c53d07c971b5e52a2563c66106,PMC,Genetic and antigenic analysis of Chlamydia pecorum strains isolated from calves with diarrhea,http://dx.doi.org/10.1292/jvms.14-0585,PMC4527498,25728336,CC BY-NC-ND,"Chlamydia pecorum (designated 22–58) was isolated in 2010 in HmLu-1 cells from the jejunum of a calf which died of necrotizing enterocolitis in Yamaguchi Prefecture, Japan. Immunohistochemical staining identified C. pecorum positive reactions in the jejunal villi. C. pecorum, designated 24–100, was isolated from the feces of a calf with diarrhea in another farm in Yamaguchi Prefecture in 2012. A significant increase in neutralizing antibody titers against C. pecorum was confirmed in paired sera. Nucleotide sequence identities of omp1 genes of the 2 isolates were 100%. The isolates were genetically and antigenically more closely related to C. pecorum Bo/Yokohama strain isolated from cattle with enteritis in Japan than to the other prototype strains, Bo/Maeda isolated from cattle with pneumonia and Ov/IPA isolated from sheep with polyarthritis. These results indicate that C. pecorum strains similar to 22–58 and 24–100 might be endemic in Yamaguchi Prefecture and cause enteric disease in cattle.",2015 Jul 27,"['OHTANI, Akifumi', 'KUBO, Masahito', 'SHIMODA, Hiroshi', 'OHYA, Kenji', 'IRIBE, Tadashi', 'OHISHI, Daiki', 'ENDOH, Daiji', 'OMATSU, Tsutomu', 'MIZUTANI, Tetsuya', 'FUKUSHI, Hideto', 'MAEDA, Ken']",J Vet Med Sci,,,True
3cb43b6223f2860048cc7bce8cb0ed0e490ddbda,PMC,Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine,http://dx.doi.org/10.1038/gt.2015.35,PMC4530203,25871827,CC BY-NC-ND,"The leishmaniases are a complex of vector-borne diseases caused by protozoan parasites of the genus Leishmania. LEISHDNAVAX is a multi-antigen, T-cell epitope-enriched DNA vaccine candidate against human leishmaniasis. The vaccine candidate has been proven immunogenic and showed prophylactic efficacy in preclinical studies. Here, we describe the safety testing of LEISHDNAVAX in naive mice and rats, complemented by the demonstration of tolerability in Leishmania-infected mice. Biodistribution and persistence were examined following single and repeated intradermal (i.d.) administration to rats. DNA vectors were distributed systemically but did not accumulate upon repeated injections. Although vector DNA was cleared from most other tissues within 60 days after the last injection, it persisted in skin at the site of injection and in draining lymph nodes. Evaluation of single-dose and repeated-dose toxicity of the vaccine candidate after i.d. administration to naive, non-infected mice did not reveal any safety concerns. LEISHDNAVAX was also well tolerated in Leishmania-infected mice. Taken together, our results substantiate a favorable safety profile of LEISHDNAVAX in both naive and infected animals and thus, support the initiation of clinical trials for both preventive and therapeutic applications of the vaccine.",2015 Aug 30,"['Riede, O', 'Seifert, K', 'Oswald, D', 'Endmann, A', 'Hock, C', 'Winkler, A', 'Salguero, F J', 'Schroff, M', 'Croft, S L', 'Juhls, C']",Gene Ther,,,True
00a00d0edc750db4a0c299dd1ec0c6871f5a4f24,PMC,Value of Analog in Medicine: Digital Compromise to Teach Old-Timer New Trick,http://dx.doi.org/10.4258/hir.2015.21.3.141,PMC4532837,26279949,CC BY-NC,,2015 Jul 31,"Cho, Hune",Healthc Inform Res,,,True
9d9704846cfede2072a22a22c7bfcd99c0470d11,PMC,Healthcare Utilization Monitoring System in Korea,http://dx.doi.org/10.4258/hir.2015.21.3.184,PMC4532843,26279955,CC BY-NC,"OBJECTIVES: It is important to monitor the healthcare utilization of patients at the national level to make evidence-based policy decisions and manage the nation's healthcare sector. The Health Insurance Review & Assessment Service (HIRA) has run a Healthcare Utilization Monitoring System (HUMS) since 2008. The objective of this paper is to introduce HIRA's HUMS. METHODS: This study described the HUMS's system structure, capacity, functionalities, and output formats run by HIRA in the Republic of Korea. Regarding output formats, this study extracted diabetes related health insurance claims through the HUMS from August 1, 2014 to May 31, 2015. RESULTS: The HUMS has kept records of health insurance claim data for 4 years. It has a 14-terabyte hardware capacity and employs several easy-to-use programs for maintenance of the system, such as MSTR, SAS, etc. Regarding functionalities, users should input diseases codes, target periods, facility types, and types of attributes, such as the number of healthcare utilizations or healthcare costs. It also has a functionality to predict healthcare utilization and costs. When this study extracted diabetes related data, it was found that the trend of healthcare costs for the treatment of diabetes and the number of patients with diabetes were increasing. CONCLUSIONS: HIRA's HUMS works well to monitor healthcare utilization of patients at the national level. The HUMS has a high-capacity hardware infrastructure and several operational programs that allows easy access to summaries as well as details to identify contributing factors for abnormality, but it has a limitation in that there is often a time lag between the provision of healthcare to patients and the filing of health claims.",2015 Jul 31,"['Shin, Hyun Chul', 'Park, Young-Taek', 'Lee, Youn Tae', 'Jo, Emmanuel C.']",Healthc Inform Res,,,True
f4c7da2c6eb641d6c76db9f8220b3f0c01850874,PMC,2015 MERS outbreak in Korea: hospital-to-hospital transmission,http://dx.doi.org/10.4178/epih/e2015033,PMC4533026,26212508,CC BY-NC,"The distinct characteristic of the Middle East Respiratory Syndrome (MERS) outbreak in South Korea is that it not only involves intra-hospital transmission, but it also involves hospital-to-hospital transmission. It has been the largest MERS outbreak outside the Middle East, with 186 confirmed cases and, among them, 36 fatal cases as of July 26, 2015. All confirmed cases are suspected to be hospital-acquired infections except one case of household transmission and two cases still undergoing examination. The Korean health care system has been the major factor shaping the unique characteristics of the outbreak. Taking this as an opportunity, the Korean government should carefully assess the fundamental problems of the vulnerability to hospital infection and make short- as well as long-term plans for countermeasures. In addition, it is hoped that this journal, Epidemiology and Health, becomes a place where various topics regarding MERS can be discussed and shared.",2015 Jul 21,"Ki, Moran",Epidemiol Health,,,True
5654f631d4fdb16992c05e76574f311f24dd506e,PMC,2015 MERS outbreak in Korea: hospital-to-hospital transmission,http://dx.doi.org/10.4178/epih/e2015033,PMC4533026,26212508,CC BY-NC,"The distinct characteristic of the Middle East Respiratory Syndrome (MERS) outbreak in South Korea is that it not only involves intra-hospital transmission, but it also involves hospital-to-hospital transmission. It has been the largest MERS outbreak outside the Middle East, with 186 confirmed cases and, among them, 36 fatal cases as of July 26, 2015. All confirmed cases are suspected to be hospital-acquired infections except one case of household transmission and two cases still undergoing examination. The Korean health care system has been the major factor shaping the unique characteristics of the outbreak. Taking this as an opportunity, the Korean government should carefully assess the fundamental problems of the vulnerability to hospital infection and make short- as well as long-term plans for countermeasures. In addition, it is hoped that this journal, Epidemiology and Health, becomes a place where various topics regarding MERS can be discussed and shared.",2015 Jul 21,"Ki, Moran",Epidemiol Health,,,False
11def60675b38fbb811f2b7a9ad62f5d938c8956,PMC,"An Outbreak of Middle East Respiratory Syndrome Coronavirus Infection in South Korea, 2015",http://dx.doi.org/10.3349/ymj.2015.56.5.1174,PMC4541644,26256957,CC BY-NC,,2015 Sep 1,"Choi, Jun Yong",Yonsei Med J,,,True
0346cb9d0f5b07fe50d9a3cc0378a53f1a87708c,PMC,Statins May Decrease the Fatality Rate of Middle East Respiratory Syndrome Infection,http://dx.doi.org/10.1128/mBio.01120-15,PMC4542194,26265720,CC BY-NC-SA,,2015 Aug 11,"Yuan, Shu",mBio,,,True
d2c536058f4f78ea00836ff72187c4c1b43e47da,PMC,The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate,http://dx.doi.org/10.1128/mBio.01013-15,PMC4542197,26286690,CC BY-NC-SA,"The 1977-1978 influenza epidemic was probably not a natural event, as the genetic sequence of the virus was nearly identical to the sequences of decades-old strains. While there are several hypotheses that could explain its origin, the possibility that the 1977 epidemic resulted from a laboratory accident has recently gained popularity in discussions about the biosafety risks of gain-of-function (GOF) influenza virus research, as an argument for why this research should not be performed. There is now a moratorium in the United States on funding GOF research while the benefits and risks, including the potential for accident, are analyzed. Given the importance of this historical epidemic to ongoing policy debates, we revisit the evidence that the 1977 epidemic was not natural and examine three potential origins: a laboratory accident, a live-vaccine trial escape, or deliberate release as a biological weapon. Based on available evidence, the 1977 strain was indeed too closely matched to decades-old strains to likely be a natural occurrence. While the origin of the outbreak cannot be conclusively determined without additional evidence, there are very plausible alternatives to the laboratory accident hypothesis, diminishing the relevance of the 1977 experience to the modern GOF debate.",2015 Aug 18,"['Rozo, Michelle', 'Gronvall, Gigi Kwik']",mBio,,,True
927e00e594ec72a344b692093b2f3f77bbd911f4,PMC,Urgent Call for Research on Middle East Respiratory Syndrome (MERS) in Korea,http://dx.doi.org/10.3961/jpmph.15.047,PMC4542295,26265662,CC BY-NC,,2015 Jul 31,"Cho, Sung-il",J Prev Med Public Health,,,True
9b91bf56210db60e68b22d502496e4b20e80ff3f,PMC,Clinical risk factors associated with the development of wheezing in children less than 2 years of age who required hospitalization for viral lower respiratory tract infections,http://dx.doi.org/10.3345/kjp.2015.58.7.245,PMC4543183,26300938,CC BY-NC,"PURPOSE: Wheezing following viral lower respiratory tract infections (LRTIs) in children <2 years of age is an important risk factor for the development of asthma later in life; however, not all children with viral LRTIs develop wheezing. This study investigated risk factors for the development of wheezing during viral LRTIs requiring hospitalization. METHODS: The study included 142 children <2 years of age hospitalized for LRTIs with at least one virus identified as the cause and classified them into children diagnosed with LRTIs with wheezing (n=70) and those diagnosed with LRTIs without wheezing (n=72). RESULTS: There were no significant differences in the viruses detected between the two groups. Multivariate logistic regression analysis showed that, after adjusting for potentially confounding variables including sex and age, the development of wheezing was strongly associated with parental history of allergic diseases (adjusted odds ratio [aOR], 20.19; 95% confidence interval [CI], 3.22-126.48), past history of allergic diseases (aOR, 13.95; 95% CI, 1.34-145.06), past history of hospitalization for respiratory illnesses (aOR, 21.36; 95% CI, 3.77-120.88), exposure to secondhand smoke at home (aOR, 14.45; 95% CI, 4.74-44.07), and total eosinophil count (aOR, 1.01; 95% CI, 1.01-1.02). CONCLUSION: Past and parental history of allergic diseases, past history of hospitalization for respiratory illnesses, exposure to secondhand smoke at home, and total eosinophil count were closely associated with the development of wheezing in children <2 years of age who required hospitalization for viral LRTIs. Clinicians should take these factors into consideration when treating, counseling, and monitoring young children admitted for viral LRTIs.",2015 Jul 22,"['Kim, Joon Hwan', 'Choi, Ji-Yeon', 'Kim, Na Yeon', 'Kim, Jin Woo', 'Baek, Ji Hyeon', 'Baek, Hye Sung', 'Yoon, Jung Won', 'Jee, Hye Mi', 'Choi, Sun Hee', 'Kim, Hyeung Yoon', 'Kim, Ki Eun', 'Shin, Youn Ho', 'Han, Man Yong']",Korean J Pediatr,,,True
7a5d731cd59597da7bcef171af936c0af4d7528c,PMC,Surveillance operation for the 141st confirmed case of Middle East Respiratory Syndrome coronavirus in response to the patient’s prior travel to Jeju Island,http://dx.doi.org/10.4178/epih/e2015035,PMC4546987,26300437,CC BY-NC,"The provincial government of Jeju, South Korea, was notified that a 42-year-old man infected with the Middle East Respiratory Syndrome (MERS) coronavirus had gone sightseeing in Jeju Island. Although the visiting period might be interpreted as the incubation period of MERS, the province decided to conduct active surveillance to prevent a worst-case scenario. Based on the channel of movement of the patient, healthy isolation and active monitoring were conducted for persons who came in contact with the patient. During the active surveillance, none of the 56 persons in self-isolation and 123 persons under active monitoring became infected. This fact supports that MERS is not contagious during the incubation period.",2015 Aug 7,"Bae, Jong-Myon",Epidemiol Health,,,True
06172d2978a367b1268754ea3cac34ca4748c9fb,PMC,Surveillance operation for the 141st confirmed case of Middle East Respiratory Syndrome coronavirus in response to the patient’s prior travel to Jeju Island,http://dx.doi.org/10.4178/epih/e2015035,PMC4546987,26300437,CC BY-NC,"The provincial government of Jeju, South Korea, was notified that a 42-year-old man infected with the Middle East Respiratory Syndrome (MERS) coronavirus had gone sightseeing in Jeju Island. Although the visiting period might be interpreted as the incubation period of MERS, the province decided to conduct active surveillance to prevent a worst-case scenario. Based on the channel of movement of the patient, healthy isolation and active monitoring were conducted for persons who came in contact with the patient. During the active surveillance, none of the 56 persons in self-isolation and 123 persons under active monitoring became infected. This fact supports that MERS is not contagious during the incubation period.",2015 Aug 7,"Bae, Jong-Myon",Epidemiol Health,,,False
2cd9f9afd98f1a4e9e01332117d6c72553e75000,PMC,A lesson learned from the MERS epidemic in Korea: an essay on MERS,http://dx.doi.org/10.4178/epih/e2015034,PMC4546989,26300436,CC BY-NC,,2015 Jul 30,"Meng, Kwang-Ho",Epidemiol Health,,,False
494052f17c7f51ee6c2e5f830eb856096635bb96,PMC,A lesson learned from the MERS epidemic in Korea: an essay on MERS,http://dx.doi.org/10.4178/epih/e2015034,PMC4546989,26300436,CC BY-NC,,2015 Jul 30,"Meng, Kwang-Ho",Epidemiol Health,,,False
091b857ba8a07eca145ae411f7202ca3a4d970df,PMC,Virus-induced secondary bacterial infection: a concise review,http://dx.doi.org/10.2147/TCRM.S87789,PMC4554399,26345407,CC BY-NC,"Respiratory diseases are a very common source of morbidity and mortality among children. Health care providers often face a dilemma when encountering a febrile infant or child with respiratory tract infection. The reason expressed by many clinicians is the trouble to confirm whether the fever is caused by a virus or a bacterium. The aim of this review is to update the current evidence on the virus-induced bacterial infection. We present several clinical as well in vitro studies that support the correlation between virus and secondary bacterial infections. In addition, we discuss the pathophysiology and prevention modes of the virus–bacterium coexistence. A search of the PubMed and MEDLINE databases was carried out for published articles covering bacterial infections associated with respiratory viruses. This review should provide clinicians with a comprehensive idea of the range of bacterial and viral coinfections or secondary infections that could present with viral respiratory illness.",2015 Aug 24,"['Hendaus, Mohamed A', 'Jomha, Fatima A', 'Alhammadi, Ahmed H']",Ther Clin Risk Manag,,,True
d062f22e831a424fc1bd0ebdbcad0175926d6038,PMC,Improving public health policy through infection transmission modelling: Guidelines for creating a Community of Practice,,PMC4556179,26361486,CC BY-NC,"BACKGROUND: Despite significant research efforts in Canada, real application of modelling in public health decision making and practice has not yet met its full potential. There is still room to better address the diversity of the Canadian population and ensure that research outcomes are translated for use within their relevant contexts. OBJECTIVES: To strengthen connections to public health practice and to broaden its scope, the Pandemic Influenza Outbreak Research Modelling team partnered with the National Collaborating Centre for Infectious Diseases to hold a national workshop. Its objectives were to: understand areas where modelling terms, methods and results are unclear; share information on how modelling can best be used in informing policy and improving practice, particularly regarding the ways to integrate a focus on health equity considerations; and sustain and advance collaborative work in the development and application of modelling in public health. METHOD: The Use of Mathematical Modelling in Public Health Decision Making for Infectious Diseases workshop brought together research modellers, public health professionals, policymakers and other experts from across the country. Invited presentations set the context for topical discussions in three sessions. A final session generated reflections and recommendations for new opportunities and tasks. CONCLUSIONS: Gaps in content and research include the lack of standard frameworks and a glossary for infectious disease modelling. Consistency in terminology, clear articulation of model parameters and assumptions, and sustained collaboration will help to bridge the divide between research and practice.",2015 Jul-Aug,"['Moghadas, Seyed M', 'Haworth-Brockman, Margaret', 'Isfeld-Kiely, Harpa', 'Kettner, Joel']",Can J Infect Dis Med Microbiol,,,True
e9ec6a0a861b00f2ead5addb565a7187163a3c07,PMC,“The Duty to Prevent” during an epidemic situation like 2015 Korean MERS outbreak,http://dx.doi.org/10.4178/epih/e2015037,PMC4558561,26493652,CC BY-NC,,2015 Aug 15,"Bae, Jong-Myon",Epidemiol Health,,,True
617197cc751a9208cb0af1b4e31baeddc8d2e985,PMC,“The Duty to Prevent” during an epidemic situation like 2015 Korean MERS outbreak,http://dx.doi.org/10.4178/epih/e2015037,PMC4558561,26493652,CC BY-NC,,2015 Aug 15,"Bae, Jong-Myon",Epidemiol Health,,,True
fa3c45e8be90553e299176c61ac7bdf1c579daed,PMC,Considerations Left behind Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Outbreaks in Republic of Korea,http://dx.doi.org/10.6118/jmm.2015.21.2.63,PMC4561741,26356871,CC BY-NC,,2015 Aug 28,"['Kim, Tae-Hee', 'Lee, Hae-Hyeog']",J Menopausal Med,,,False
975a8b4abe4cc0181522e859a92c5ddc22f50c29,PMC,A questionnaire-based survey on the uptake and use of cattle vaccines in the UK,http://dx.doi.org/10.1136/vropen-2014-000042,PMC4562447,26392877,CC BY-NC,"BACKGROUND: Vaccination is a widely used strategy for disease control in cattle in the UK and abroad. However, there has been limited research describing the uptake and use of cattle vaccines on UK farms. AIM: To describe the current uptake and usage of cattle vaccines in the UK. DESIGN: A questionnaire, available in paper and online format, was distributed to cattle farmers by convenience sampling. PARTICIPANTS: All UK cattle farmers were eligible to participate in the study. RESULTS: Eighty-six per cent of respondents (n=229/266) had vaccinated their cattle in the past year. Diseases most commonly vaccinated against were Bovine Viral Diarrhoea, Leptospirosis and Infectious Bovine Rhinotracheitis. Vaccination compliance was limited in certain areas, for example only 48 per cent of respondents stated that they administered the second dose in the primary course within the recommended timeframe, and 14 per cent of respondents stated that they vaccinated earlier than the youngest recommended age. Although outside the scope of this study, further work is needed to establish the extent of inadequate compliance and the effect this has on vaccine efficacy. The role of the veterinarian was highlighted as the main supplier of vaccines and preferred source of vaccination information. Respondents preferred to receive recommendations regarding vaccination by face-to-face communication with the veterinarian. CONCLUSIONS: The results provide a description of the current uptake and usage of cattle vaccines in the UK. Uptake is generally high but there are areas of usage of vaccines which could be improved upon. The veterinarian plays a key role as supplier of vaccines and a source of information for the majority of farmers. Although outside the scope of this study, further work is needed to establish the extent of inadequate compliance and the effect this has on vaccine efficacy. Although the respondents in this study represent a biased population of farmers, the findings indicate areas for future investigation in order to improve vaccination strategies in cattle in the UK.",2014 Jul 11,"['Cresswell, E.', 'Brennan, M. L.', 'Barkema, H. W.', 'Wapenaar, W.']",Vet Rec Open,,,True
e2d29009210b2e9a2e3273cb541c7298b1bbb3cb,PMC,"Comparative Analysis of Host Cell Entry of Ebola Virus From Sierra Leone, 2014, and Zaire, 1976",http://dx.doi.org/10.1093/infdis/jiv101,PMC4564534,25840443,CC BY-NC-ND,"The ongoing Ebola virus (EBOV) disease (EVD) epidemic in Western Africa is the largest EVD outbreak recorded to date and requires the rapid development and deployment of antiviral measures. The viral glycoprotein (GP) facilitates host cell entry and, jointly with cellular interaction partners, constitutes a potential target for antiviral intervention. However, it is unknown whether the GPs of the currently and previously circulating EBOVs use the same mechanisms for cellular entry and are thus susceptible to inhibition by the same antivirals and cellular defenses. Here, we show that the GPs of the EBOVs circulating in 1976 and 2014 transduce the same spectrum of target cells, use the same cellular factors for host cell entry, and are comparably susceptible to blockade by antiviral interferon-induced transmembrane proteins and neutralizing antibody KZ52. Thus, the viruses responsible for the ongoing EVD epidemic should be fully susceptible to established antiviral strategies targeting GP and cellular entry factors.",2015 Oct 1,"['Hofmann-Winkler, Heike', 'Gnirß, Kerstin', 'Wrensch, Florian', 'Pöhlmann, Stefan']",J Infect Dis,,,True
02522a1b4512e4d2880a6a551a8dff589d4cb393,PMC,Analysis of Ebola Virus Entry Into Macrophages,http://dx.doi.org/10.1093/infdis/jiv140,PMC4564540,25877552,CC BY-NC-ND,"Ebolaviruses constitute a public health threat, particularly in Central and Western Africa. Host cell factors required for spread of ebolaviruses may serve as targets for antiviral intervention. Lectins, TAM receptor tyrosine kinases (Tyro3, Axl, Mer), T cell immunoglobulin and mucin domain (TIM) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruses into certain cellular systems. However, the factors used by ebolaviruses to invade macrophages, major viral targets, are poorly defined. Here, we show that mannose-specific lectins, TIM-1 and Axl augment entry into certain cell lines but do not contribute to Ebola virus (EBOV)-glycoprotein (GP)–driven transduction of macrophages. In contrast, expression of Mer, integrin αV, and NPC1 was required for efficient GP-mediated transduction and EBOV infection of macrophages. These results define cellular factors hijacked by EBOV for entry into macrophages and, considering that Mer and integrin αV promote phagocytosis of apoptotic cells, support the concept that EBOV relies on apoptotic mimicry to invade target cells.",2015 Oct 1,"['Dahlmann, Franziska', 'Biedenkopf, Nadine', 'Babler, Anne', 'Jahnen-Dechent, Willi', 'Karsten, Christina B.', 'Gnirß, Kerstin', 'Schneider, Heike', 'Wrensch, Florian', ""O'Callaghan, Christopher A."", 'Bertram, Stephanie', 'Herrler, Georg', 'Becker, Stephan', 'Pöhlmann, Stefan', 'Hofmann-Winkler, Heike']",J Infect Dis,,,True
4b55b2415bd2adff96e6013f792d281693bf4587,PMC,Interferon-Induced Transmembrane Protein–Mediated Inhibition of Host Cell Entry of Ebolaviruses,http://dx.doi.org/10.1093/infdis/jiv255,PMC4564551,26034199,CC BY-NC-ND,"Ebolaviruses are highly pathogenic in humans and nonhuman primates and pose a severe threat to public health. The interferon-induced transmembrane (IFITM) proteins can restrict entry of ebolaviruses, influenza A viruses, and other enveloped viruses. However, the breadth and mechanism of the antiviral activity of IFITM proteins are incompletely understood. Here, we employed ebolavirus glycoprotein–pseudotyped vectors and ebolavirus-like particles to address this question. We show that IFITM proteins inhibit the cellular entry of diverse ebolaviruses and demonstrate that type I interferon induces IFITM protein expression in macrophages, major viral targets. Moreover, we show that IFITM proteins block entry of influenza A viruses and ebolaviruses by different mechanisms and provide evidence that antibodies and IFITM proteins can synergistically inhibit cellular entry of ebolaviruses. These results provide insights into the role of IFITM proteins in infection by ebolaviruses and suggest a mechanism by which antibodies, though poorly neutralizing in vitro, might contribute to viral control in vivo.",2015 Oct 1,"['Wrensch, Florian', 'Karsten, Christina B.', 'Gnirß, Kerstin', 'Hoffmann, Markus', 'Lu, Kai', 'Takada, Ayato', 'Winkler, Michael', 'Simmons, Graham', 'Pöhlmann, Stefan']",J Infect Dis,,,True
62f8fe75756cfe9bee96096f566d79994b7ff5de,PMC,Repurposing paclitaxel for the treatment of fibrosis: indication discovery for existing drugs,http://dx.doi.org/10.2147/DDDT.S87771,PMC4567211,26379422,CC BY-NC,,2015 Sep 7,"['Chen, Xiao-Wu', 'Duan, Wei', 'Zhou, Shu-Feng']",Drug Des Devel Ther,,,True
dab074e75c2dae02b60e8094aa5a06e553122831,PMC,Protection conferred by live infectious bronchitis vaccine viruses against variant Middle East IS/885/00-like and IS/1494/06-like isolates in commercial broiler chicks,http://dx.doi.org/10.1136/vetreco-2014-000111,PMC4567785,26392909,CC BY-NC,"The ability of the infectious bronchitis H120 (a Massachusetts strain) and CR88 (a 793B strain) live attenuated vaccine viruses to protect from two Middle East infectious bronchitis virus isolates, IS/885/00-like (IS/885) and IS/1494/06-like (IS/1494) in broiler chicks was investigated. Day-old chicks were separated into three groups, (I) vaccinated with H120 at day-old followed by CR88 at 14 days-old, (II) vaccinated with H120 and CR88 simultaneously at day-old and again with CR88 at 14 days-old, (III) control unvaccinated. At 30 days-old, each of the groups was challenged with virulent IS/885 or IS/1494. Protection was evaluated based on the clinical signs, tracheal and kidney gross lesions and tracheal ciliostasis. Results showed that administering combined live H120 and CR88 vaccines simultaneously at day-old followed by CR88 vaccine at 14 days-old gave more than 80 per cent tracheal ciliary protection from both of the Middle East isolates. In addition, this programme conferred 100 per cent protection from clinical signs and tracheal or kidney lesions. The other vaccination programme, H120 at day-old followed by CR88 at 14 days-old, the tracheal ciliary protection conferred were 60 per cent and 80 per cent from IS/885/00-like and IS/1494/06-like, respectively.",2015 Sep 9,"['Awad, Faez', 'Forrester, Anne', 'Baylis, Matthew', 'Lemiere, Stephane', 'Ganapathy, Kannan']",Vet Rec Open,,,True
c70bdcb5ad0df2ac48e9e00f7c35625b7e90557d,PMC,H1N1 Influenza Pandemic in Italy Revisited: Has the Willingness to Get Vaccinated Suffered in the Long Run?,http://dx.doi.org/10.4081/jphr.2015.559,PMC4568430,26425501,CC BY-NC,"BACKGROUND: The aim of the study is to assess the long-term secondary effects of personal experience with the H1N1 pandemic of 2009/2010 and the perception of the institutional reaction to it on Italians’ willingness to get vaccinated in case of a novel influenza pandemic. DESIGN AND METHODS: We conducted 140 face-to-face interviews in the Registry Office of the Municipality of Milan, Italy, from October to December 2012. RESULTS: Willingness to get vaccinated during a novel influenza pandemic was best predicted by having been vaccinated against the seasonal flu in the past (OR=5.18; 95%CI: 1.40 to 19.13) and fear of losing one’s life in case of an infection with H1N1 (OR=4.09; 95%CI: 1.68 to 9.97). It was unaffected by the assessment of institutional performance. CONCLUSIONS: The findings of this study do not point to long-term secondary effects of the institutional handling of the H1N1 pandemic. The results highlight the fact that behavioural intention is not the same as behaviour, and that the former cannot simply be taken as an indicator of the latter.",2015 Sep 4,"['Ludolph, Ramona', 'Nobile, Marta', 'Hartung, Uwe', 'Castaldi, Silvana', 'Schulz, Peter J.']",J Public Health Res,,,True
f1ed23f642ae10aad709176ea8025687b34d5c27,PMC,Changes in Clinical Presentation and Epidemiology of Respiratory Pathogens Associated With Acute Respiratory Illness in Military Trainees After Reintroduction of Adenovirus Vaccine,http://dx.doi.org/10.1093/ofid/ofv120,PMC4569648,26380351,CC BY-NC-ND,"Background. Adenovirus (Ad) has long been the predominant cause of acute respiratory illness (ARI) in military trainees. In 2011, live oral Ad vaccines for serotypes 4 and 7 were reintroduced into US basic military training populations. This study evaluated the impact on clinical presentations and other respiratory pathogens. Methods. The Center for Advanced Molecular Detection at Joint Base San Antonio-Lackland prospectively collects demographic, clinical, and polymerase chain reaction data from respiratory specimens (throat swab and nasal wash) among Air Force trainees presenting for care of ARI. Results. From June 2008 to August 2013, 2660 trainees enrolled and were tested for selected respiratory pathogens. Post-vaccine introduction (VI), reported systemic symptoms were less frequent, including fever (38% vs 94%) and myalgia (37% vs 67%; P < .01). Median temperature and heart rate decreased (98.4 vs 101.3°F, 81 vs 96 beats per minute; P < .01). Ad detection decreased for all Ad (3% vs 68%), Ad4 (1% vs 70%), 7 (0% vs 8%), 14 (0% vs 5%), and 3 (0.1% vs 2%); P < .01). Rhinovirus and cases with no pathogen identified increased in frequency (35% vs 18%, 51% vs 14%; P < .01). Conclusions. Acute respiratory illness in military trainees post-VI is associated with decreased severity of systemic symptoms and reduced fever and heart rate. Marked reductions in frequency of Ad serotypes are seen, including those in the vaccine, with no serotype shift. However, detection of several other respiratory pathogens, most notably rhinovirus, is observed in increasing proportions, and a majority are now undiagnosed clinical syndromes.",2015 Sep 1,"['Yun, Heather C.', 'Young, Adam N.', 'Caballero, Manuel Y.', 'Lott, Lisa', 'Cropper, Thomas L.', 'Murray, Clinton K.']",Open Forum Infect Dis,,,True
381d5feb501bd762182e76a3fcb4dd3f64c9a261,PMC,A sensitive and specific antigen detection assay for Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1038/emi.2015.26,PMC4575394,26421268,CC BY-NC-SA,"Since its emergence in 2012, more than 900 laboratory-confirmed cases of Middle East respiratory syndrome (MERS) have been reported with a fatality rate of more than 30%. However, no antigen detection assay for commercial use is available for diagnosis. In this study, the full-length nucleocapsid protein (NP) gene of MERS coronavirus (MERS-CoV) was cloned and expressed in Escherichia coli. A MERS-CoV NP capture enzyme-linked immunosorbent assay (ELISA) using two MERS-CoV-NP-specific monoclonal antibodies (MAbs) generated was developed. The ELISA was evaluated using 129 nasopharyngeal aspirates (NPAs) positive for various respiratory viruses and simulated positive NPAs by adding serial dilutions of MERS-CoV. Using a cutoff OD of 0.19, all 129 NPAs positive for respiratory viruses showed very low OD, with a specificity of 100%. For the two simulated MERS-CoV-positive NPAs with serial dilutions of live MERS-CoV, all samples with ≥10 50% tissue culture infective dose (TCID(50))/0.1 mL showed positive results. For the 10 additional NPAs with 20 and 200 TCID(50)/0.1 mL of live MERS-CoV added, all were positive. A highly sensitive and specific MAbs-based antigen capture ELISA has been developed for MERS. This sensitive and specific antigen capture ELISA should be useful for detection of MERS-CoV in human and dromedaries and in field studies.",2015 Apr 22,"['Chen, Yixin', 'Chan, Kwok-Hung', 'Kang, Yahong', 'Chen, Honglin', 'Luk, Hayes KH', 'Poon, Rosana WS', 'Chan, Jasper FW', 'Yuen, Kwok-Yung', 'Xia, Ningshao', 'Lau, Susanna KP', 'Woo, Patrick CY']",Emerg Microbes Infect,,,True
a3abdec780d11a40fb6740ebaa730dfd313a1106,PMC,"Essential oil of Artemisia vestita exhibits potent in vitro and in vivo antibacterial activity: Investigation of the effect of oil on biofilm formation, leakage of potassium ions and survival curve measurement",http://dx.doi.org/10.3892/mmr.2015.4210,PMC4581751,26259564,CC BY-NC-ND,"The aim of the present study was to investigate the chemical composition of the essential oil of Artemisia vestita and to determine the antibacterial activity of the essential oil and its two major components, grandisol and 1,8-cineole, against certain respiratory infection-causing bacterial strains, in vitro and in vivo. The chemical composition of the essential oil was analyzed using gas chromatography-mass spectrometry. A micro-well dilution method was used to determine the minimum inhibition concentration (MIC) values of the essential oil and its major constituents. A model of Streptococcus pyogenes infection in mice was used to determine its in vivo activities. Lung and blood samples were obtained to assess bacterial cell counts. Toxicity evaluation of the essential oil and its components was completed by performing biochemical analysis of the serum, particularly monitoring aspartate transaminase, alanine transaminase, urea and creatinine. The essential oil exhibited potent antibacterial activity, whereas the two major constituents were less potent. The essential oil exhibited MIC values between 20 and 80 μg/ml, while the values of the two constituents were between 130 and 200 μg/ml. Scanning electron microscopy results demonstrated that the essential oil inhibited biofilm formation and altered its architecture. Survival curves indicated that the essential oil led to a reduction in the viability of different bacteria. The essential oil also induced significant leakage of potassium ions from S. pyogenes. The essential oil (100 μg/mouse) and grandisol (135 μg/mouse) significantly reduced the number of viable bacterial cells in the lungs (P<0.01). However, intake of 100 μg/mouse of essential oil or grandisol 135 μg/mouse once or twice each day for 9 days did not produce any toxic effects in the mice. In conclusion, the in vitro and in vivo results suggested that the essential oil of A. vestita and one of its major constituents, grandisol, can significantly inhibit the growth of different bacterial strains.",2015 Oct 11,"['YANG, CHANG', 'HU, DONG-HUI', 'FENG, YAN']",Mol Med Rep,,,True
680adbe0c280f4774383793afb8b70fd9ab3d5d0,PMC,"Use of Padlock Probes and Rolling Circle Amplification (RCA) for Rapid Identification of Trichophyton Species, Related to Human and Animal Disorder",http://dx.doi.org/10.5812/jjm.19107v2,PMC4584133,26421127,CC BY-NC,"BACKGROUND: The high degree of phenotypic similarity among Trichophyton species makes their identification difficult. OBJECTIVES: The current study aims to establish the use of rolling circle amplification (RCA) based on internal transcribed spacer ribosomal DNA (ITS rDNA) as a powerful, simple, and rapid procedure for distinguishing closely related organisms, and specifically to identify Trichophyton species, which cause human and animal disorders. MATERIALS AND METHODS: A total of sixty-one isolates belonging to three species of Trichophyton were identified to the species level based on microscopic and macroscopic examinations and their ITS rDNA regions were sequenced. Three specific circular oligonucleotide probes targeting the ITS1 and ITS2 regions were designed to differentiate Trichophyton rubrum, T. mentagrophytes, and T. tonsurans. RESULTS: Of the 61 putative Trichophyton clinical isolates, 52 were identified to the species level. The most common species was T. mentagrophytes var. interdigitale (31 isolates), followed by T. rubrum (11 isolates), T. tonsurans (9 isolates), and T. violaceum (1 isolates); moreover, 9 isolates were identified as non-Trichophyton species. The RCA method correctly identified four Trichophyton species and was 100% specific for each species. Neither cross-reaction between the examined species of Trichophyton nor false positive or false negative results were observed. CONCLUSIONS: Species identification of Trichophyton is crucially important for epidemiological and phylogenetic purposes and for genotype delineation. RCA based on ITS polymorphisms can be used to generate identification barcodes and as an alternative to DNA sequencing; it is a very fast, specific, and economical tool for species identification.",2015 Jul 27,"['Zakeri, Hamideh', 'Shokohi, Tahereh', 'Badali, Hamid', 'Mayahi, Saba', 'Didehdar, Mojtaba']",Jundishapur J Microbiol,,,True
d8452b6817c6ae38d642d42f6177244fa06d3bd6,PMC,A multiplex quantitative real-time polymerase chain reaction panel for detecting neurologic pathogens in dogs with meningoencephalitis,http://dx.doi.org/10.4142/jvs.2015.16.3.341,PMC4588020,26040611,CC BY-NC,"Meningoencephalitis (ME) is a common inflammatory disorder of the central nervous system in dogs. Clinically, ME has both infectious and non-infectious causes. In the present study, a multiplex quantitative real-time polymerase chain reaction (mqPCR) panel was optimized for the detection of eight canine neurologic pathogens (Blastomyces dermatitidis, Cryptococcus spp., Neospora caninum, Borrelia burgdorferi, Bartonella spp., Toxoplasma gondii, Ehrlichia canis, and canine distemper virus [CDV]). The mqPCR panel was subsequently applied to 53 cerebrospinal fluid (CSF) samples collected from dogs with ME. The analytic sensitivity (i.e., limit of detection, expressed as molecules per 1 µL of recombinant vector) was 3.8 for CDV, 3.7 for Ehrlichia canis, 3.7 for Bartonella spp., 3.8 for Borrelia burgdorferi, 3.7 for Blastomyces dermatitidis, 3.7 for Cryptococcus spp., 38 for Neospora caninum, and 3.7 for Toxoplasma gondii. Among the tested CSF samples, seven (15%) were positive for the following pathogens in decreasing order of frequency: Cryptococcus spp. (3/7), Blastomyces dermatitidis (2/7), and Borrelia burgdorferi (2/7). In summary, use of an mqPCR panel with high analytic sensitivity as an initial screen for infectious agents in dogs with ME could facilitate the selection of early treatment strategies and improve outcomes.",2015 Sep 21,"['Han, Jae-Ik', 'Chang, Dong-Woo', 'Na, Ki-Jeong']",J Vet Sci,,,True
b10c26fb4aa979ef7068dd295b28176e2fe5a692,PMC,Outbreak of Middle East Respiratory Syndrome in Korea?,http://dx.doi.org/10.1016/j.phrp.2015.08.005,PMC4588446,26473088,CC BY-NC-ND,,2015 Aug 28,"['Cho, Hae-Wol', 'Chu, Chaeshin']",Osong Public Health Res Perspect,,,False
61d0aa9a148a88e0354e36508c925eeb87a6b685,PMC,Metagenomic ventures into outer sequence space,http://dx.doi.org/10.4161/21597081.2014.979664,PMC4588555,26458273,CC BY-NC,"Sequencing DNA or RNA directly from the environment often results in many sequencing reads that have no homologs in the database. These are referred to as “unknowns,"" and reflect the vast unexplored microbial sequence space of our biosphere, also known as “biological dark matter."" However, unknowns also exist because metagenomic datasets are not optimally mined. There is a pressure on researchers to publish and move on, and the unknown sequences are often left for what they are, and conclusions drawn based on reads with annotated homologs. This can cause abundant and widespread genomes to be overlooked, such as the recently discovered human gut bacteriophage crAssphage. The unknowns may be enriched for bacteriophage sequences, the most abundant and genetically diverse component of the biosphere and of sequence space. However, it remains an open question, what is the actual size of biological sequence space? The de novo assembly of shotgun metagenomes is the most powerful tool to address this question.",2014 Dec 15,"Dutilh, Bas E",Bacteriophage,,,True
70b3836f7b7cc9c445be26a0b3de2455711c7a39,PMC,Enhancing production of ergosterol in Pichia pastoris GS115 by over-expression of 3-hydroxy-3-methylglutaryl CoA reductase from Glycyrrhiza uralensis,http://dx.doi.org/10.1016/j.apsb.2014.02.007,PMC4590296,26579379,CC BY-NC-ND,"The rate-limiting enzyme in the mevalonic acid (MVA) pathway which can lead to triterpenoid saponin glycyrrhizic acid (GA) is 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR). In order to reveal the effect of copy number variation in the HMGR gene on the MVA pathway, the HMGR gene from Glycyrrhiza uralensis Fisch. (GuHMGR) was cloned and over-expressed in Pichia pastoris GS115. Six recombinant P. pastoris strains containing different copy numbers of the GuHMGR gene were obtained and the content of ergosterol was analyzed by HPLC. The results showed that all the recombinant P. pastoris strains contained more ergosterol than the negative control and the strains with 8 and 44 copies contained significantly more ergosterol than the other strains. However, as the copy number increased, the content of ergosterol showed an increasing–decreasing–increasing pattern. This study provides a rationale for increasing the content of GA through over-expressing the GuHMGR gene in cultivars of G. uralensis.",2014 Apr 2,"['Liu, Ying', 'Zhu, Xiaoqing', 'Li, Wendong', 'Wen, Hao', 'Gao, Ya', 'Liu, Yong', 'Liu, Chunsheng']",Acta Pharm Sin B,,,False
ca2fa034524ce26d06b3674b3c494635d7d5f13b,PMC,Real time detection of farm-level swine mycobacteriosis outbreak using time series modeling of the number of condemned intestines in abattoirs,http://dx.doi.org/10.1292/jvms.14-0675,PMC4591155,25913899,CC BY-NC-ND,"Mycobacteriosis in swine is a common zoonosis found in abattoirs during meat inspections, and the veterinary authority is expected to inform the producer for corrective actions when an outbreak is detected. The expected value of the number of condemned carcasses due to mycobacteriosis therefore would be a useful threshold to detect an outbreak, and the present study aims to develop such an expected value through time series modeling. The model was developed using eight years of inspection data (2003 to 2010) obtained at 2 abattoirs of the Higashi-Mokoto Meat Inspection Center, Japan. The resulting model was validated by comparing the predicted time-dependent values for the subsequent 2 years with the actual data for 2 years between 2011 and 2012. For the modeling, at first, periodicities were checked using Fast Fourier Transformation, and the ensemble average profiles for weekly periodicities were calculated. An Auto-Regressive Integrated Moving Average (ARIMA) model was fitted to the residual of the ensemble average on the basis of minimum Akaike’s information criterion (AIC). The sum of the ARIMA model and the weekly ensemble average was regarded as the time-dependent expected value. During 2011 and 2012, the number of whole or partial condemned carcasses exceeded the 95% confidence interval of the predicted values 20 times. All of these events were associated with the slaughtering of pigs from three producers with the highest rate of condemnation due to mycobacteriosis.",2015 Sep 24,"['ADACHI, Yasumoto', 'MAKITA, Kohei']",J Vet Med Sci,,,True
25a01c665ab20de80b75d48a2f71081666bca429,PMC,"MERS epidemiological investigation to detect potential mode of transmission in the 178th MERS confirmed case in Pyeongtaek, Korea",http://dx.doi.org/10.4178/epih/e2015036,PMC4591909,26493651,CC BY-NC,"Most cases of Middle East Respiratory Syndrome (MERS) infection in Korea (outbreak: May 11-July 4, 2015) occurred in hospital settings, with uncertain transmission modes in some cases. We performed an in-depth investigation epidemiological survey on the 178th case to determine the precise mode of transmission. A 29- year-old man living in Pyeongtaek presented on June 16 with a febrile sensation, chills, and myalgia. Upon confirmatory diagnosis on June 23, he was treated in an isolation room and discharged on July 2 after cure. An epidemiological investigation of all possible infection routes indicated two likely modes of transmission: exposure to MERS in Pyeongtaek St. Mary’s Hospital during a visit to his hospitalized father (May 18-29), and infection through frequent contact with his father between the latter’s referral to Pyeongtaek Good Samaritan Bagae Hospital for treatment without confirmatory diagnosis until his death (May 29-June 6). Although lack of clear proof or evidence to the contrary does not allow a definitive conclusion, all other possibilities could be excluded by epidemiological inferences. While it is impossible to trace back the modes of transmission of all cases in a large-scale outbreak, case-by-case tracking and isolation of infected individuals and those in close contact with them is important in preventing the spread. Efforts should be made to establish a methodology for rapid tracking of all possible contacts and elimination-based identification of the precise modes of transmission.",2015 Aug 15,"['Chang, Kyujin', 'Ki, Moran', 'Lee, Eun Gyu', 'Lee, Soon Young', 'Yoo, Byoungin', 'Choi, Jong Hyuk']",Epidemiol Health,,,True
76257b1d43b639f1b0704cd82b77c593f2a1a65c,PMC,"MERS epidemiological investigation to detect potential mode of transmission in the 178th MERS confirmed case in Pyeongtaek, Korea",http://dx.doi.org/10.4178/epih/e2015036,PMC4591909,26493651,CC BY-NC,"Most cases of Middle East Respiratory Syndrome (MERS) infection in Korea (outbreak: May 11-July 4, 2015) occurred in hospital settings, with uncertain transmission modes in some cases. We performed an in-depth investigation epidemiological survey on the 178th case to determine the precise mode of transmission. A 29- year-old man living in Pyeongtaek presented on June 16 with a febrile sensation, chills, and myalgia. Upon confirmatory diagnosis on June 23, he was treated in an isolation room and discharged on July 2 after cure. An epidemiological investigation of all possible infection routes indicated two likely modes of transmission: exposure to MERS in Pyeongtaek St. Mary’s Hospital during a visit to his hospitalized father (May 18-29), and infection through frequent contact with his father between the latter’s referral to Pyeongtaek Good Samaritan Bagae Hospital for treatment without confirmatory diagnosis until his death (May 29-June 6). Although lack of clear proof or evidence to the contrary does not allow a definitive conclusion, all other possibilities could be excluded by epidemiological inferences. While it is impossible to trace back the modes of transmission of all cases in a large-scale outbreak, case-by-case tracking and isolation of infected individuals and those in close contact with them is important in preventing the spread. Efforts should be made to establish a methodology for rapid tracking of all possible contacts and elimination-based identification of the precise modes of transmission.",2015 Aug 15,"['Chang, Kyujin', 'Ki, Moran', 'Lee, Eun Gyu', 'Lee, Soon Young', 'Yoo, Byoungin', 'Choi, Jong Hyuk']",Epidemiol Health,,,False
95c40fb092ef550e2c0d8316a3af2d6c025df87d,PMC,Adult-onset Kawasaki disease (mucocutaneous lymph node syndrome) and concurrent Coxsackievirus A4 infection: a case report,http://dx.doi.org/10.2147/IMCRJ.S90685,PMC4599061,26491373,CC BY-NC,"INTRODUCTION: Kawasaki disease (KD) most commonly develops in infants, although its specific cause is still unclear. We report here a rare case of adult-onset KD which revealed to be concurrently infected by Coxsackievirus A4. CASE PRESENTATION: The patient was a 37-year-old Japanese man who presented with fever, exanthema, changes in the peripheral extremities, bilateral non-exudative conjunctival injection, and changes in the oropharynx, signs that meet the diagnostic criteria for KD defined by the Centers for Disease Control and Prevention. In this case, the patient had a significantly high antibody titer for Coxsackievirus A4, which led us to presume that the occurrence of KD was concurrent Coxsackievirus A4 infection. CONCLUSION: We reported a very rare case of KD which suggests that the disease can be concurrent Coxsackievirus A4 infection. Although KD is an acute childhood disease, with fever as one of the principal features, KD should also be considered in the differential diagnosis when adult patients present with a fever of unknown cause associated with a rash.",2015 Sep 29,"['Ueda, Yuki', 'Kenzaka, Tsuneaki', 'Noda, Ayako', 'Yamamoto, Yu', 'Matsumura, Masami']",Int Med Case Rep J,,,True
d5f6841f61ab1b11599f16043c48b9268be6e134,PMC,Origin and Possible Genetic Recombination of the Middle East Respiratory Syndrome Coronavirus from the First Imported Case in China: Phylogenetics and Coalescence Analysis,http://dx.doi.org/10.1128/mBio.01280-15,PMC4600111,26350969,CC BY-NC-SA,"The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe acute respiratory tract infection with a high fatality rate in humans. Coronaviruses are capable of infecting multiple species and can evolve rapidly through recombination events. Here, we report the complete genomic sequence analysis of a MERS-CoV strain imported to China from South Korea. The imported virus, provisionally named ChinaGD01, belongs to group 3 in clade B in the whole-genome phylogenetic tree and also has a similar tree topology structure in the open reading frame 1a and -b (ORF1ab) gene segment but clusters with group 5 of clade B in the tree constructed using the S gene. Genetic recombination analysis and lineage-specific single-nucleotide polymorphism (SNP) comparison suggest that the imported virus is a recombinant comprising group 3 and group 5 elements. The time-resolved phylogenetic estimation indicates that the recombination event likely occurred in the second half of 2014. Genetic recombination events between group 3 and group 5 of clade B may have implications for the transmissibility of the virus.",2015 Sep 8,"['Wang, Yanqun', 'Liu, Di', 'Shi, Weifeng', 'Lu, Roujian', 'Wang, Wenling', 'Zhao, Yanjie', 'Deng, Yao', 'Zhou, Weimin', 'Ren, Hongguang', 'Wu, Jun', 'Wang, Yu', 'Wu, Guizhen', 'Gao, George F.', 'Tan, Wenjie']",mBio,,,True
b46366da5d99bcda034e32fa230def76f9aadf3f,PMC,Origin and Possible Genetic Recombination of the Middle East Respiratory Syndrome Coronavirus from the First Imported Case in China: Phylogenetics and Coalescence Analysis,http://dx.doi.org/10.1128/mBio.01280-15,PMC4600111,26350969,CC BY-NC-SA,"The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe acute respiratory tract infection with a high fatality rate in humans. Coronaviruses are capable of infecting multiple species and can evolve rapidly through recombination events. Here, we report the complete genomic sequence analysis of a MERS-CoV strain imported to China from South Korea. The imported virus, provisionally named ChinaGD01, belongs to group 3 in clade B in the whole-genome phylogenetic tree and also has a similar tree topology structure in the open reading frame 1a and -b (ORF1ab) gene segment but clusters with group 5 of clade B in the tree constructed using the S gene. Genetic recombination analysis and lineage-specific single-nucleotide polymorphism (SNP) comparison suggest that the imported virus is a recombinant comprising group 3 and group 5 elements. The time-resolved phylogenetic estimation indicates that the recombination event likely occurred in the second half of 2014. Genetic recombination events between group 3 and group 5 of clade B may have implications for the transmissibility of the virus.",2015 Sep 8,"['Wang, Yanqun', 'Liu, Di', 'Shi, Weifeng', 'Lu, Roujian', 'Wang, Wenling', 'Zhao, Yanjie', 'Deng, Yao', 'Zhou, Weimin', 'Ren, Hongguang', 'Wu, Jun', 'Wang, Yu', 'Wu, Guizhen', 'Gao, George F.', 'Tan, Wenjie']",mBio,,,False
eb3a7845dfe449de5d2656100f2d39ced09dcb1b,PMC,Origin and Possible Genetic Recombination of the Middle East Respiratory Syndrome Coronavirus from the First Imported Case in China: Phylogenetics and Coalescence Analysis,http://dx.doi.org/10.1128/mBio.01280-15,PMC4600111,26350969,CC BY-NC-SA,"The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe acute respiratory tract infection with a high fatality rate in humans. Coronaviruses are capable of infecting multiple species and can evolve rapidly through recombination events. Here, we report the complete genomic sequence analysis of a MERS-CoV strain imported to China from South Korea. The imported virus, provisionally named ChinaGD01, belongs to group 3 in clade B in the whole-genome phylogenetic tree and also has a similar tree topology structure in the open reading frame 1a and -b (ORF1ab) gene segment but clusters with group 5 of clade B in the tree constructed using the S gene. Genetic recombination analysis and lineage-specific single-nucleotide polymorphism (SNP) comparison suggest that the imported virus is a recombinant comprising group 3 and group 5 elements. The time-resolved phylogenetic estimation indicates that the recombination event likely occurred in the second half of 2014. Genetic recombination events between group 3 and group 5 of clade B may have implications for the transmissibility of the virus.",2015 Sep 8,"['Wang, Yanqun', 'Liu, Di', 'Shi, Weifeng', 'Lu, Roujian', 'Wang, Wenling', 'Zhao, Yanjie', 'Deng, Yao', 'Zhou, Weimin', 'Ren, Hongguang', 'Wu, Jun', 'Wang, Yu', 'Wu, Guizhen', 'Gao, George F.', 'Tan, Wenjie']",mBio,,,False
509eaf8fb436b60e6d84da002b3630d62b39309e,PMC,Middle East Respiratory Syndrome Coronavirus Recombination and the Evolution of Science and Public Health in China,http://dx.doi.org/10.1128/mBio.01381-15,PMC4600119,26350973,CC BY-NC-SA,,2015 Sep 8,"Lipkin, W. Ian",mBio,,,True
b416c44441bd1db0d8d535fa8046434a4ba0a357,PMC,Acute Necrotizing Pancreatitis Associated with Mycoplasma pneumoniae Infection in a Child,http://dx.doi.org/10.5223/pghn.2015.18.3.209,PMC4600707,26473143,CC BY-NC,"Mycoplasma pneumoniae is responsible for approximately 20% to 30% of community-acquired pneumonia, and is well known for its diverse extrapulmonary manifestations. However, acute necrotizing pancreatits is an extremely rare extrapulmonary manifestation of M. pneumoniae infection. A 6-year-old girl was admitted due to abdominal pain, vomiting, fever, and confused mentality. Acute necrotizing pancreatitis was diagnosed according to symptoms, laboratory test results, and abdominal computed tomography scans. M. pneumoniae infection was diagnosed by a 4-fold increase in antibodies to M. pneumoniae between acute and convalescent sera by particle agglutination antibody assay. No other etiologic factors or pathogens were detected. Despite the occurrence of a large infected pseudocyst during the course, the patient was able to discharge without morbidity by early aggressive supportive care. This is the first case in Korea of a child with acute necrotizing pancreatitis associated with M. pneumoniae infection.",2015 Sep 25,"['Yang, Aram', 'Kang, Ben', 'Choi, So Yoon', 'Cho, Joong Bum', 'Kim, Yae-Jean', 'Jeon, Tae Yeon', 'Choe, Yon Ho']",Pediatr Gastroenterol Hepatol Nutr,,,True
9a0f63b592a07e5823715e548da6f3605faf2bbb,PMC,Multiplex SYBR Green Real-Time PCR Assay for Detection of Respiratory Viruses,http://dx.doi.org/10.5812/jjm.19041v2,PMC4601230,26468358,CC BY-NC,"BACKGROUND: It is often difficult for a physician to distinguish between viral and bacterial causes of respiratory infections and this may result in overuse of antibiotics. In many cases of community-acquired respiratory infections, clinicians treat patients empirically. The development of molecular methods for direct detection of viruses has been progressed recently. OBJECTIVES: The objective of this study was recognizing the panel of respiratory RNA viruses by multiplex SYBR Green real-time polymerase chain reaction (PCR). MATERIALS AND METHODS: Randomized 172 influenza-negative respiratory specimens of all age groups of hospitalized patients were collected. After RNA extraction, cDNA was synthesized. Three SYBR Green multiplex real-time PCR assays were developed for simultaneous detection of 12 respiratory RNA viruses. Each set of multiplex methods detected four viruses, the first set: respiratory syncytial virus, human metapneumovirus, rhinovirus, enterovirus; the second set: parainfluenza viruses 1 - 4 (PIV1-4); the third set: coronaviruses NL63, 229E, severe acute respiratory syndrome (SARS), and OC43. RESULTS: Application of the multiplex SYBR Green real-time PCR in clinical samples from 172 patients in a one-year study resulted in detection of 19 (11.04%) PIV3, 9 (5.23%) PIV4, and 1 (0.58%) coronavirus NL63. All the positive samples were detected during December to March (2011 - 2012). CONCLUSIONS: Multiplex SYBR Green real-time PCR is a rapid and relatively inexpensive method for detection of respiratory viruses.",2015 Aug 1,"['Sultani, Mozhdeh', 'Mokhtari Azad, Talat', 'Eshragian, Mohammadreza', 'Shadab, Azadeh', 'Naseri, Maryam', 'Eilami, Owrang', 'Yavarian, Jila']",Jundishapur J Microbiol,,,True
58b95b98f9016190301e31fa9809932a4d8169c2,PMC,"Detection of Viral and Bacterial Pathogens in Hospitalized Children With Acute Respiratory Illnesses, Chongqing, 2009–2013",http://dx.doi.org/10.1097/MD.0000000000000742,PMC4602679,25906103,CC BY-NC,"Acute respiratory infections (ARIs) cause large disease burden each year. The codetection of viral and bacterial pathogens is quite common; however, the significance for clinical severity remains controversial. We aimed to identify viruses and bacteria in hospitalized children with ARI and the impact of mixed detections. Hospitalized children with ARI aged ≤16 were recruited from 2009 to 2013 at the Children's Hospital of Chongqing Medical University, Chongqing, China. Nasopharyngeal aspirates (NPAs) were collected for detection of common respiratory viruses by reverse transcription polymerase chain reaction (RT-PCR) or PCR. Bacteria were isolated from NPAs by routine culture methods. Detection and codetection frequencies and clinical features and severity were compared. Of the 3181 hospitalized children, 2375 (74.7%) were detected with ≥1 virus and 707 (22.2%) with ≥1 bacteria, 901 (28.3%) with ≥2 viruses, 57 (1.8%) with ≥2 bacteria, and 542 (17.0%) with both virus and bacteria. The most frequently detected were Streptococcus pneumoniae, respiratory syncytial virus, parainfluenza virus, and influenza virus. Clinical characteristics were similar among different pathogen infections for older group (≥6 years old), with some significant difference for the younger. Cases with any codetection were more likely to present with fever; those with ≥2 virus detections had higher prevalence of cough; cases with virus and bacteria codetection were more likely to have cough and sputum. No significant difference in the risk of pneumonia, severe pneumonia, and intensive care unit admission were found for any codetection than monodetection. There was a high codetection rate of common respiratory pathogens among hospitalized pediatric ARI cases, with fever as a significant predictor. Cases with codetection showed no significant difference in severity than those with single pathogens.",2015 Apr 24,"['Wei, Lan', 'Liu, Wei', 'Zhang, Xiao-Ai', 'Liu, En-Mei', 'Wo, Yin', 'Cowling, Benjamin J.', 'Cao, Wu-Chun']",Medicine (Baltimore),,,True
bf5b3c8ca8f08950a6402469badcb792bed09e21,PMC,Integrating behavioral surveillance into emerging infectious disease prevention,http://dx.doi.org/10.1093/trstmh/trv080,PMC4603270,26464229,CC BY-NC,,2015 Nov 9,"Miller, Maureen",Trans R Soc Trop Med Hyg,,,True
a2add35b84a53cbad3301093f4191d5edadf1d0e,PMC,Role of Clinical Endoscopy in Emphasizing Endoscope Disinfection,http://dx.doi.org/10.5946/ce.2015.48.5.351,PMC4604269,26473114,CC BY-NC,"Based on the unexpected Middle East respiratory syndrome (MERS) outbreak in Korea, it was established that the virus can spread easily, MERS exposure in hospitals carries an extreme risk for infection as well as mortality, and the sharing of information was essential for infection control. Although the incidence of exogenous infections related to contaminated endoscopes is very low, the majority of published outbreaks have been caused by various shortcomings in reprocessing procedures, including insufficient training or awareness. Ever since the inauguration of ""Clinical Endoscopy"" as an English-language journal of the Korean Society of Gastrointestinal Endoscopy in 2011, it has published several articles on disinfection of the endoscope and its accessories. Many Science Citation Index journals have also emphasized high-level disinfection of the gastrointestinal endoscope. Many papers have been produced specifically, since the outbreak of carbapenem-resistant Enterobacteriaceae in 2013. The recent review papers concluded that quality control is the most important issue among all the aspects of procedural care, including the efficiency of the gastrointestinal endoscopy unit and reprocessing room. Thorough reprocessing of endoscopes using high-level disinfection and sterilization methods may be essential for reducing the risk of infection.",2015 Sep 30,"['Ryu, Ji Kon', 'Kim, Eun Young', 'Kwon, Kwang An', 'Choi, Il Ju', 'Hahm, Ki Baik']",Clin Endosc,,,True
a8dd4ad790014376cbea595be02bc5cade42104f,PMC,Antiviral Treatment Guidelines for Middle East Respiratory Syndrome,http://dx.doi.org/10.3947/ic.2015.47.3.212,PMC4607778,26483999,CC BY-NC,"Middle East respiratory syndrome (MERS) is an acute infectious disease of the respiratory system caused by the new betacoronavirus (MERS coronavirus, MERS-CoV), which shows high mortality rates. The typical symptoms of MERS are fever, cough, and shortness of breath, and it is often accompanied by pneumonia. The MERS-CoV was introduced to Republic of Korea in May 2015 by a patient returning from Saudi Arabia. The disease spread mostly through hospital infections, and by the time the epidemic ended in August, the total number of confirmed diagnoses was 186, among which 36 patients died. Reflecting the latest evidence for antiviral drugs in the treatment of MERS-CoV infection and the experiences of treating MERS patients in Republic of Korea, these guidelines focus on antiviral drugs to achieve effective treatment of MERS-CoV infections.",2015 Sep 30,"['Chong, Yong Pil', 'Song, Joon Young', 'Seo, Yu Bin', 'Choi, Jae-Phil', 'Shin, Hyoung-Shik', None]",Infect Chemother,,,True
bfe6cc567549b7922e6d17d202e5e35501d4d606,PMC,Antiviral Treatment Guidelines for Middle East Respiratory Syndrome,http://dx.doi.org/10.3947/ic.2015.47.3.212,PMC4607778,26483999,CC BY-NC,"Middle East respiratory syndrome (MERS) is an acute infectious disease of the respiratory system caused by the new betacoronavirus (MERS coronavirus, MERS-CoV), which shows high mortality rates. The typical symptoms of MERS are fever, cough, and shortness of breath, and it is often accompanied by pneumonia. The MERS-CoV was introduced to Republic of Korea in May 2015 by a patient returning from Saudi Arabia. The disease spread mostly through hospital infections, and by the time the epidemic ended in August, the total number of confirmed diagnoses was 186, among which 36 patients died. Reflecting the latest evidence for antiviral drugs in the treatment of MERS-CoV infection and the experiences of treating MERS patients in Republic of Korea, these guidelines focus on antiviral drugs to achieve effective treatment of MERS-CoV infections.",2015 Sep 30,"['Chong, Yong Pil', 'Song, Joon Young', 'Seo, Yu Bin', 'Choi, Jae-Phil', 'Shin, Hyoung-Shik', None]",Infect Chemother,,,True
a24b5a764c19d383dbfe795779b18799c6d2f4e9,PMC,Expression and Purification of the Uropathogenic Escherichia coli PapG Protein and its Surface Absorption on Lactobacillus reuteri: Implications for Surface Display System Vaccines,http://dx.doi.org/10.5812/jjm.25595,PMC4609037,26487922,CC BY-NC,"BACKGROUND: Uropathogenic Escherichia coli (UPEC) is one of the most common bacteria that can cause urinary tract infections (UTIs). Unfortunately, no human vaccine against UTIs has been developed. Therefore, it is necessary to develop an efficient and safe vaccine that is able to induce mucosal and systemic immune responses. The use of lactic acid bacteria as a delivery system is a promising method to induce the immune system. OBJECTIVES: The aim of this study was to establish Lactobacillus reuteri harboring the E. coli PapG antigen on its surface. MATERIALS AND METHODS: In this study, the gene encoding PapG was fused to the AcmA gene (which encodes an anchor protein in Lactobacillus) and cloned into the pEX A vector. The PapG.AcmA fusion gene was digested with BamHI and NdeI and sub-cloned into the pET21a expression vector at the digestion sites. Subsequently, the recombinant plasmids (pET21a-PapG.AcmA and pET21a-PapG) were transformed into the E. coli Origami strain using the calcium chloride method and the fusion protein was expressed under 1 mM IPTG induction. The expression of the fusion protein was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting. Purification of the PapG and PapG.AcmA proteins was carried out using a Ni-NTA column, and surface adsorption was estimated on Lactobacillus. Finally, surface localization of the fusion protein was verified by an enzyme-linked immunosorbent assay (ELISA). RESULTS: The PapG.AcmA fusion was successfully sub-cloned in the pET21a expression vector. The expression of PapG and PapG.AcmA proteins in the E. coli Origami strain was indicated as protein bands in SDS-PAGE and confirmed by western blotting. In addition, the fusion protein was displayed on the surface of L. reuteri. CONCLUSIONS: In conclusion, we developed a method to express the PapG.AcmA protein on the surface of Lactobacillus. This is the first report on the successful application of lactic acid bacteria displaying the PapG.AcmA fusion protein. It will be interesting to determine the immune responses against the PapG protein in near future using this surface display strategy.",2015 Sep 8,"['Ashrafi, Fatemeh', 'Fallah Mehrabadi, Jalil', 'Siadat, Seyed Davar', 'Aghasadeghi, Mohammad Reza']",Jundishapur J Microbiol,,,True
d48ae48fa33c489b576489afc16c00f5b1532178,PMC,Virome Capture Sequencing Enables Sensitive Viral Diagnosis and Comprehensive Virome Analysis,http://dx.doi.org/10.1128/mBio.01491-15,PMC4611031,26396248,CC BY-NC-SA,"Insensitivity and technical complexity have impeded the implementation of high-throughput nucleic acid sequencing in differential diagnosis of viral infections in clinical laboratories. Here, we describe the development of a virome capture sequencing platform for vertebrate viruses (VirCapSeq-VERT) that increases the sensitivity of sequence-based virus detection and characterization. The system uses ~2 million probes that cover the genomes of members of the 207 viral taxa known to infect vertebrates, including humans. A biotinylated oligonucleotide library was synthesized on the NimbleGen cleavable array platform and used for solution-based capture of viral nucleic acids present in complex samples containing variable proportions of viral and host nucleic acids. The use of VirCapSeq-VERT resulted in a 100- to 10,000-fold increase in viral reads from blood and tissue homogenates compared to conventional Illumina sequencing using established virus enrichment procedures, including filtration, nuclease treatments, and RiboZero rRNA subtraction. VirCapSeq-VERT had a limit of detection comparable to that of agent-specific real-time PCR in serum, blood, and tissue extracts. Furthermore, the method identified novel viruses whose genomes were approximately 40% different from the known virus genomes used for designing the probe library. The VirCapSeq-VERT platform is ideally suited for analyses of virome composition and dynamics. Importance  VirCapSeq-VERT enables detection of viral sequences in complex sample backgrounds, including those found in clinical specimens, such as serum, blood, and tissue. The highly multiplexed nature of the system allows both the simultaneous identification and the comprehensive genetic characterization of all known vertebrate viruses, their genetic variants, and novel viruses. The operational simplicity and efficiency of the VirCapSeq-VERT platform may facilitate transition of high-throughput sequencing to clinical diagnostic as well as research applications.",2015 Sep 22,"['Briese, Thomas', 'Kapoor, Amit', 'Mishra, Nischay', 'Jain, Komal', 'Kumar, Arvind', 'Jabado, Omar J.', 'Lipkin, W. Ian']",mBio,,,True
5d78b139da9ef9b2070d532b2bd773c367656ca8,PMC,Identification of a Natural Viral RNA Motif That Optimizes Sensing of Viral RNA by RIG-I,http://dx.doi.org/10.1128/mBio.01265-15,PMC4611036,26443454,CC BY-NC-SA,"Stimulation of the antiviral response depends on the sensing of viral pathogen-associated molecular patterns (PAMPs) by specialized cellular proteins. During infection with RNA viruses, 5′-di- or -triphosphates accompanying specific single or double-stranded RNA motifs trigger signaling of intracellular RIG-I-like receptors (RLRs) and initiate the antiviral response. Although these molecular signatures are present during the replication of many viruses, it is unknown whether they are sufficient for strong activation of RLRs during infection. Immunostimulatory defective viral genomes (iDVGs) from Sendai virus (SeV) are among the most potent natural viral triggers of antiviral immunity. Here we describe an RNA motif (DVG(70-114)) that is essential for the potent immunostimulatory activity of 5′-triphosphate-containing SeV iDVGs. DVG(70-114) enhances viral sensing by the host cell independently of the long stretches of complementary RNA flanking the iDVGs, and it retains its stimulatory potential when transferred to otherwise inert viral RNA. In vitro analysis showed that DVG(70-114) augments the binding of RIG-I to viral RNA and promotes enhanced RIG-I polymerization, thereby facilitating the onset of the antiviral response. Together, our results define a new natural viral PAMP enhancer motif that promotes viral recognition by RLRs and confers potent immunostimulatory activity to viral RNA.",2015 Oct 6,"['Xu, Jie', 'Mercado-López, Xiomara', 'Grier, Jennifer T.', 'Kim, Won-keun', 'Chun, Lauren F.', 'Irvine, Edward B.', 'Del Toro Duany, Yoandris', 'Kell, Alison', 'Hur, Sun', 'Gale, Michael', 'Raj, Arjun', 'López, Carolina B.']",mBio,,,True
7d23656771268d325fc276045ff002b7d0184e7b,PMC,Reply to “Statins may decrease the Fatality Rate of MERS Infection”,http://dx.doi.org/10.1128/mBio.01303-15,PMC4611038,26419878,CC BY-NC-SA,,2015 Sep 29,"['Totura, Allison L.', 'Baric, Ralph S.']",mBio,,,True
fa3906f048a58d703a5baff91a6545518cbcf4b7,PMC,The 1977 H1N1 Influenza Virus Reemergence Demonstrated Gain-of-Function Hazards,http://dx.doi.org/10.1128/mBio.01434-15,PMC4611044,26419881,CC BY-NC-SA,,2015 Sep 29,"Furmanski, Martin",mBio,,,True
2a584d39eb8b164d066dbc8e7496c9a9ff39bc30,PMC,Critical role of phospholipase A(2) group IID in age-related susceptibility to severe acute respiratory syndrome–CoV infection,http://dx.doi.org/10.1084/jem.20150632,PMC4612096,26392224,CC BY-NC-SA,"Oxidative stress and chronic low-grade inflammation in the lungs are associated with aging and may contribute to age-related immune dysfunction. To maintain lung homeostasis, chronic inflammation is countered by enhanced expression of proresolving/antiinflammatory factors. Here, we show that age-dependent increases of one such factor in the lungs, a phospholipase A(2) (PLA(2)) group IID (PLA(2)G2D) with antiinflammatory properties, contributed to worse outcomes in mice infected with severe acute respiratory syndrome-coronavirus (SARS-CoV). Strikingly, infection of mice lacking PLA(2)G2D expression (Pla2g2d(−/−) mice) converted a uniformly lethal infection to a nonlethal one (>80% survival), subsequent to development of enhanced respiratory DC migration to the draining lymph nodes, augmented antivirus T cell responses, and diminished lung damage. We also observed similar effects in influenza A virus–infected middle-aged Pla2g2d(−/−) mice. Furthermore, oxidative stress, probably via lipid peroxidation, was found to induce PLA(2)G2D expression in mice and in human monocyte–derived macrophages. Thus, our results suggest that directed inhibition of a single inducible phospholipase, PLA(2)G2D, in the lungs of older patients with severe respiratory infections is potentially an attractive therapeutic intervention to restore immune function.",2015 Oct 19,"['Vijay, Rahul', 'Hua, Xiaoyang', 'Meyerholz, David K.', 'Miki, Yoshimi', 'Yamamoto, Kei', 'Gelb, Michael', 'Murakami, Makoto', 'Perlman, Stanley']",J Exp Med,,,True
18e3b16784c0c1660f87b927e9f0782f6f2e2327,PMC,Critical role of phospholipase A(2) group IID in age-related susceptibility to severe acute respiratory syndrome–CoV infection,http://dx.doi.org/10.1084/jem.20150632,PMC4612096,26392224,CC BY-NC-SA,"Oxidative stress and chronic low-grade inflammation in the lungs are associated with aging and may contribute to age-related immune dysfunction. To maintain lung homeostasis, chronic inflammation is countered by enhanced expression of proresolving/antiinflammatory factors. Here, we show that age-dependent increases of one such factor in the lungs, a phospholipase A(2) (PLA(2)) group IID (PLA(2)G2D) with antiinflammatory properties, contributed to worse outcomes in mice infected with severe acute respiratory syndrome-coronavirus (SARS-CoV). Strikingly, infection of mice lacking PLA(2)G2D expression (Pla2g2d(−/−) mice) converted a uniformly lethal infection to a nonlethal one (>80% survival), subsequent to development of enhanced respiratory DC migration to the draining lymph nodes, augmented antivirus T cell responses, and diminished lung damage. We also observed similar effects in influenza A virus–infected middle-aged Pla2g2d(−/−) mice. Furthermore, oxidative stress, probably via lipid peroxidation, was found to induce PLA(2)G2D expression in mice and in human monocyte–derived macrophages. Thus, our results suggest that directed inhibition of a single inducible phospholipase, PLA(2)G2D, in the lungs of older patients with severe respiratory infections is potentially an attractive therapeutic intervention to restore immune function.",2015 Oct 19,"['Vijay, Rahul', 'Hua, Xiaoyang', 'Meyerholz, David K.', 'Miki, Yoshimi', 'Yamamoto, Kei', 'Gelb, Michael', 'Murakami, Makoto', 'Perlman, Stanley']",J Exp Med,,,False
cf410c7fd76487d1244517521fbe521465e75310,PMC,Ebola Hemorrhagic Fever as a Public Health Emergency of International Concern; a Review Article,,PMC4614609,26512362,CC BY-NC,"Ebola hemorrhagic fever (EHF) was first reported in 1976 with two concurrent outbreaks of acute viral hemorrhagic fever centered in Yambuku (near the Ebola river), Democratic Republic of Congo, and in Nzara, Sudan. The current outbreak of the Ebola virus was started by reporting the first case in March 2014 in the forest regions of southeastern Guinea. Due to infection rates raising over 13,000% within a 6-month period, Ebola is now considered as a global public health emergency and on August 8(th), 2014 the World Health Organization (WHO) declared the epidemic to be a Public Health Emergency of International Concern. With more than 5000 involved cases and nearly 3000 deaths, this event has turned into the largest and most dangerous Ebola virus outbreak in the world. Based on the above-mentioned, the present article aimed to review the virologic characteristics, transmission, clinical manifestation, diagnosis, treatment, and prevention of Ebola virus disease.",2015 Winter,"['Safari, Saeed', 'Baratloo, Alireza', 'Rouhipour, Alaleh', 'Ghelichkhani, Parisa', 'Yousefifard, Mahmood']",Emerg (Tehran),,,True
d00f4dabc58eca254f3b2ca4efafda00d671c3da,PMC,Cell cycle control (and more) by programmed −1 ribosomal frameshifting: implications for disease and therapeutics,http://dx.doi.org/10.4161/15384101.2014.989123,PMC4615106,25584829,CC BY-NC,"Like most basic molecular mechanisms, programmed –1 ribosomal frameshifting (−1 PRF) was first identified in viruses. Early observations that global dysregulation of −1 PRF had deleterious effects on yeast cell growth suggested that −1 PRF may be used to control cellular gene expression, and the cell cycle in particular. Collection of sufficient numbers of viral −1 PRF signals coupled with advances in computer sciences enabled 2 complementary computational approaches to identify −1 PRF signals in free living organisms. The unexpected observation that almost all −1 PRF events on eukaryotic mRNAs direct ribosomes to premature termination codons engendered the hypothesis that −1 PRF signals post-transcriptionally regulate gene expression by functioning as mRNA destabilizing elements. Emerging research suggests that some human diseases are associated with global defects in −1 PRF. The recent discovery of −1 PRF signal-specific trans-acting regulators may provide insight into novel therapeutic strategies aimed at treating diseases caused by changes in gene expression patterns.",2015 Jan 13,"['Belew, Ashton T', 'Dinman, Jonathan D']",Cell Cycle,,,True
0f67baef306ea56d7b574059fb72ff68affb0246,PMC,RNA methyltransferases involved in 5′ cap biosynthesis,http://dx.doi.org/10.1080/15476286.2015.1004955,PMC4615557,25626080,CC BY-NC,"In eukaryotes and viruses that infect them, the 5′ end of mRNA molecules, and also many other functionally important RNAs, are modified to form a so-called cap structure that is important for interactions of these RNAs with many nuclear and cytoplasmic proteins. The RNA cap has multiple roles in gene expression, including enhancement of RNA stability, splicing, nucleocytoplasmic transport, and translation initiation. Apart from guanosine addition to the 5′ end in the most typical cap structure common to transcripts produced by RNA polymerase II (in particular mRNA), essentially all cap modifications are due to methylation. The complexity of the cap structure and its formation can range from just a single methylation of the unprocessed 5′ end of the primary transcript, as in mammalian U6 and 7SK, mouse B2, and plant U3 RNAs, to an elaborate m(7)Gpppm(6,6)AmpAmpCmpm(3)Um structure at the 5′ end of processed RNA in trypanosomes, which are formed by as many as 8 methylation reactions. While all enzymes responsible for methylation of the cap structure characterized to date were found to belong to the same evolutionarily related and structurally similar Rossmann Fold Methyltransferase superfamily, that uses the same methyl group donor, S-adenosylmethionine; the enzymes also exhibit interesting differences that are responsible for their distinct functions. This review focuses on the evolutionary classification of enzymes responsible for cap methylation in RNA, with a focus on the sequence relationships and structural similarities and dissimilarities that provide the basis for understanding the mechanism of biosynthesis of different caps in cellular and viral RNAs. Particular attention is paid to the similarities and differences between methyltransferases from human cells and from human pathogens that may be helpful in the development of antiviral and antiparasitic drugs.",2015 Jan 27,"['Byszewska, Magdalena', 'Śmietański, Mirosław', 'Purta, Elżbieta', 'Bujnicki, Janusz M']",RNA Biol,,,True
3e1874b3a7b354af8cb25bfcd127ba887afe92c2,PMC,A New Quaternary Structure Epitope on Dengue Virus Serotype 2 Is the Target of Durable Type-Specific Neutralizing Antibodies,http://dx.doi.org/10.1128/mBio.01461-15,PMC4620467,26463165,CC BY-NC-SA,"Dengue virus serotype 2 (DENV2) is widespread and responsible for severe epidemics. While primary DENV2 infections stimulate serotype-specific protective responses, a leading vaccine failed to induce a similar protective response. Using human monoclonal antibodies (hMAbs) isolated from dengue cases and structure-guided design of a chimeric DENV, here we describe the major site on the DENV2 envelope (E) protein targeted by neutralizing antibodies. DENV2-specific neutralizing hMAb 2D22 binds to a quaternary structure epitope. We engineered and recovered a recombinant DENV4 that displayed the 2D22 epitope. DENV2 neutralizing antibodies in people exposed to infection or a live vaccine tracked with the 2D22 epitope on the DENV4/2 chimera. The chimera remained sensitive to DENV4 antibodies, indicating that the major neutralizing epitopes on DENV2 and -4 are at different sites. The ability to transplant a complex epitope between DENV serotypes demonstrates a hitherto underappreciated structural flexibility in flaviviruses, which could be harnessed to develop new vaccines and diagnostics.",2015 Oct 13,"['Gallichotte, E. N.', 'Widman, D. G.', 'Yount, B. L.', 'Wahala, W. M.', 'Durbin, A.', 'Whitehead, S.', 'Sariol, C. A.', 'Crowe, J. E.', 'de Silva, A. M.', 'Baric, R. S.']",mBio,,,True
0adc0c7498f0ebbb3c8f1c662da34605d5f91fe2,PMC,Respiratory infectious phenotypes in acute exacerbation of COPD: an aid to length of stay and COPD Assessment Test,http://dx.doi.org/10.2147/COPD.S92160,PMC4621204,26527871,CC BY-NC,"PURPOSE: To investigate the respiratory infectious phenotypes and their impact on length of stay (LOS) and the COPD Assessment Test (CAT) Scale in acute exacerbation of COPD (AECOPD). PATIENTS AND METHODS: We categorized 81 eligible patients into bacterial infection, viral infection, coinfection, and non-infectious groups. The respiratory virus examination was determined by a liquid bead array xTAG Respiratory Virus Panel in pharyngeal swabs, while bacterial infection was studied by conventional sputum culture. LOS and CAT as well as demographic information were recorded. RESULTS: Viruses were detected in 38 subjects, bacteria in 17, and of these, seven had both. Influenza virus was the most frequently isolated virus, followed by enterovirus/rhinovirus, coronavirus, bocavirus, metapneumovirus, parainfluenza virus types 1, 2, 3, and 4, and respiratory syncytial virus. Bacteriologic analyses of sputum showed that Pseudomonas aeruginosa was the most common bacteria, followed by Acinetobacter baumannii, Klebsiella, Escherichia coli, and Streptococcus pneumoniae. The longest LOS and the highest CAT score were detected in coinfection group. CAT score was positively correlated with LOS. CONCLUSION: Respiratory infection is a common causative agent of exacerbations in COPD. Respiratory coinfection is likely to be a determinant of more severe acute exacerbations with longer LOS. CAT score may be a predictor of longer LOS in AECOPD.",2015 Oct 20,"['Dai, Meng-Yuan', 'Qiao, Jin-Ping', 'Xu, Yuan-Hong', 'Fei, Guang-He']",Int J Chron Obstruct Pulmon Dis,,,True
b9fea1c9572c3309b431eb3f883cdd05973193cd,PMC,"Antibody engineering and therapeutics conference: The annual meeting of the antibody society, Huntington Beach, CA, December 7–11, 2014",http://dx.doi.org/10.4161/19420862.2014.971627,PMC4622443,25517297,CC BY-NC,"The 25(th) anniversary of the Antibody Engineering & Therapeutics Conference, the Annual Meeting of The Antibody Society, will be held in Huntington Beach, CA, December 7–11, 2014. Organized by IBC Life Sciences, the event will celebrate past successes, educate participants on current activities and offer a vision of future progress in the field. Keynote addresses will be given by academic and industry experts Douglas Lauffenburger (Massachusetts Institute of Technology), Ira Pastan (National Cancer Institute), James Wells (University of California, San Francisco), Ian Tomlinson (GlaxoSmithKline) and Anthony Rees (Rees Consulting AB and Emeritus Professor, University of Bath). These speakers will provide updates of their work, placed in the context of the substantial growth of the industry over the past 25 years.",2014 Oct 29,"['Larrick, James W', 'Parren, Paul WHI', 'Huston, James S', 'Plückthun, Andreas', 'Bradbury, Andrew', 'Tomlinson, Ian M', 'Chester, Kerry A', 'Burton, Dennis R', 'Adams, Gregory P', 'Weiner, Louis M', 'Scott, Jamie K', 'Alfenito, Mark R', 'Veldman, Trudi', 'Reichert, Janice M']",MAbs,,,False
6bb0038a55ff68a2f47a36e8c845126da7fea61b,PMC,Effect of cadmium on the expression levels of interleukin-1α and interleukin-10 cytokines in human lung cells,http://dx.doi.org/10.3892/mmr.2015.4316,PMC4626121,26397147,CC BY-NC-ND,"Cadmium is an environmentally hazardous metal, which causes toxicity in humans. Inhalation of cigarette smoke and industrial fumes containing cadmium are sources of cadmium exposure. It is responsible for the malfunction of various organs, leading to disease particularly in the lungs, liver and kidneys. In the present study, the effect of cadmium chloride (CdCl(2)) on cell viability, and the expression levels of interleukin (IL)-1α and IL-10 cytokines at various concentrations and incubation durations were assessed in MRC-9 human normal lung and A549 human lung cancer cells to elucidate the mechanism of cadmium toxicity. Cell viability was measured using a crystal violet dye binding assay. The expression levels of the cytokines were measured by cytokine specific enzyme-linked immunosorbent assay kits. The viability assay results revealed higher sensitivity of the A549 lung cancer cells to CdCl(2) compared with the normal MRC-9 lung cells. In the normal MRC-9 lung cells, higher expression levels of the cytokines were observed at the lowest CdCl(2) concentration at a shorter exposure time compared with the lung cancer cells. Higher levels of the cytokines were observed in the A549 lung cancer cells at all other times and concentrations compared with the MRC-9 cells, indicating higher levels of inflammation. The cytokine levels were reduced at higher CdCl(2) concentrations and longer exposure durations, demonstrating the toxic effect of cadmium. The results indicated that CdCl(2) affected the expression levels of the cytokines and led to cytotoxicity in human lung cells, and suggested that compounds which reduce inflammation may prevent cadmium toxicity.",2015 Nov 10,"['ODEWUMI, CAROLINE', 'LATINWO, LEKAN M.', 'SINCLAIR, ANDRE', 'BADISA, VEERA L.D.', 'ABDULLAH, AHKINYALA', 'BADISA, RAMESH B.']",Mol Med Rep,,,True
a8fb010702e647142d24caeeb5572e1e67c9fbd5,PMC,Expression and purification of functional HMGB1 A box by fusion with SUMO,http://dx.doi.org/10.3892/mmr.2015.4308,PMC4626187,26352592,CC BY-NC-ND,"High-mobility-group-box chromosomal protein 1 (HMGB1) is a ubiquitous and abundant nuclear protein in eukaryotic cells. Nuclear HMGB1 serves an important role in maintaining nuclear stability under stress. However, extracellular HMGB1 exerts actions, which are distinctly different compared with these intracellular functions. HMGB1, when released extracellularly, is a potent innate signal, which initiates host defense mechanisms or tissue regeneration. HMGB1 has two DNA-binding domains: HMG A box and B box. The HMGB1 A box exhibits an antagonistic, anti-inflammatory effect, and is a potential therapeutic target, however, the large-scale expression and purification of the HMGB1 A box with high efficiency remains to be reported. In the present study, a SUMO-fusion expression system was used to express and purify high levels of functional HMGB1 A box to meet the requirements of therapeutic protein production.",2015 Nov 9,"['GE, WEN-SONG', 'FAN, JIAN-GAO', 'CHEN, YING-WEI', 'XU, LEI-MING']",Mol Med Rep,,,True
fab32444594a7c25009ffcd48e91c923f5f0316f,PMC,The imperative to develop a human vaccine for the Hendra virus in Australia,http://dx.doi.org/10.3402/iee.v5.29619,PMC4627939,26519254,CC BY-NC,"The Hendra virus (HeV) poses a significant challenge to public health in Australia. Expanding migratory patterns observed among bats and the mutation of the virus to seek and successfully infect new hosts is a significant departure from the generalized epidemiological trend. The recent discovery of equine-related infections and deaths in addition to a canine infection demonstrates the inadequacy of the current equine vaccine developed in 2012. Traditional models for controlling the spread of the vector are futile given the rapid pace at which bats' habitats are eroded. Recent ongoing zoonotic epidemics, for example, Ebola and Middle East respiratory syndrome coronavirus, demonstrate that human-to-human transmission is a distinct reality rather than an obscure possibility. The development of a human HeV vaccine is essential for the biosecurity of Australia, as part of a multipronged strategy to control HeV in Australia.",2015 Oct 29,"['Zahoor, Bilal A.', 'Mudie, Lucy I.']",Infect Ecol Epidemiol,,,True
5d242f75fdf42da4059b45f0b7e407da675418e2,PMC,A cell-based high-throughput approach to identify inhibitors of influenza A virus,http://dx.doi.org/10.1016/j.apsb.2014.06.005,PMC4629080,26579399,CC BY-NC-ND,"Influenza is one of the most common infections threatening public health worldwide and is caused by the influenza virus. Rapid emergence of drug resistance has led to an urgent need to develop new anti-influenza inhibitors. In this study we established a 293T cell line that constitutively synthesizes a virus-based negative strand RNA, which expresses Gaussia luciferase upon influenza A virus infection. Using this cell line, an assay was developed and optimized to search for inhibitors of influenza virus replication. Biochemical studies and statistical analyses presented herein demonstrate the sensitivity and reproducibility of the assay in a high-throughput format (Z′ factor value>0.8). A pilot screening provides further evidence for validation of the assay. Taken together, this work provides a simple, convenient, and reliable HTS assay to identify compounds with anti-influenza activity.",2014 Aug 14,"['Gao, Qian', 'Wang, Zhen', 'Liu, Zhenlong', 'Li, Xiaoyu', 'Zhang, Yongxin', 'Zhang, Zhizhen', 'Cen, Shan']",Acta Pharm Sin B,,,False
ab234077589d919717101e45e6bc45c29a1a242d,PMC,Interactions among SARS-CoV accessory proteins revealed by bimolecular fluorescence complementation assay,http://dx.doi.org/10.1016/j.apsb.2015.05.002,PMC4629423,26579480,CC BY-NC-ND,"The accessory proteins (3a, 3b, 6, 7a, 7b, 8a, 8b, 9b and ORF14), predicted unknown proteins (PUPs) encoded by the genes, are considered to be unique to the severe acute respiratory syndrome coronavirus (SARS-CoV) genome. These proteins play important roles in various biological processes mediated by interactions with their partners. However, very little is known about the interactions among these accessory proteins. Here, a EYFP (enhanced yellow fluorescent protein) bimolecular fluorescence complementation (BiFC) assay was used to detect the interactions among accessory proteins. 33 out of 81 interactions were identified by BiFC, much more than that identified by the yeast two-hybrid (Y2H) system. This is the first report describing direct visualization of interactions among accessory proteins of SARS-CoV. These findings attest to the general applicability of the BiFC system for the verification of protein-protein interactions.",2015 Sep 6,"['Kong, Jianqiang', 'Shi, Yanwei', 'Wang, Zhifang', 'Pan, Yiting']",Acta Pharm Sin B,,,False
1c468d9576bd22e199c4fe2028856afabb3746a7,PMC,"Parainfluenza Virus Infection Among Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Children and Adults Hospitalized for Severe Acute Respiratory Illness in South Africa, 2009–2014",http://dx.doi.org/10.1093/ofid/ofv139,PMC4630450,26566534,CC BY-NC-ND,"Background. Parainfluenza virus (PIV) is a common cause of acute respiratory tract infections, but little is known about PIV infection in children and adults in Africa, especially in settings where human immunodeficiency virus (HIV) prevalence is high. Methods. We conducted active, prospective sentinel surveillance for children and adults hospitalized with severe acute respiratory illness (SARI) from 2009 to 2014 in South Africa. We enrolled controls (outpatients without febrile or respiratory illness) to calculate the attributable fraction for PIV infection. Respiratory specimens were tested by multiplex real-time reverse-transcription polymerase chain reaction assay for parainfluenza types 1, 2, and 3. Results. Of 18 282 SARI cases enrolled, 1188 (6.5%) tested positive for any PIV type: 230 (19.4%) were type 1; 168 (14.1%) were type 2; 762 (64.1%) were type 3; and 28 (2.4%) had coinfection with 2 PIV types. After adjusting for age, HIV serostatus, and respiratory viral coinfection, the attributable fraction for PIV was 65.6% (95% CI [confidence interval], 47.1–77.7); PIV contributed to SARI among HIV-infected and -uninfected children <5 years of age and among individuals infected with PIV types 1 and 3. The observed overall incidence of PIV-associated SARI was 38 (95% CI, 36–39) cases per 100 000 population and was highest in children <1 year of age (925 [95% CI, 864–989] cases per 100 000 population). Compared with persons without HIV, persons with HIV had an increased relative risk of PIV hospitalization (9.4; 95% CI, 8.5–10.3). Conclusions. Parainfluenza virus causes substantial severe respiratory disease in South Africa among children <5 years of age, especially those that are infected with HIV.",2015 Sep 19,"['Cohen, Adam L.', 'Sahr, Philip K.', 'Treurnicht, Florette', 'Walaza, Sibongile', 'Groome, Michelle J.', 'Kahn, Kathleen', 'Dawood, Halima', 'Variava, Ebrahim', 'Tempia, Stefano', 'Pretorius, Marthi', 'Moyes, Jocelyn', 'Olorunju, Steven A. S.', 'Malope-Kgokong, Babatyi', 'Kuonza, Lazarus', 'Wolter, Nicole', 'von Gottberg, Anne', 'Madhi, Shabir A.', 'Venter, Marietjie', 'Cohen, Cheryl']",Open Forum Infect Dis,,,True
fce3506fcb7fa163babc7f4e959283ecbe346bc9,PMC,"Middle East Respiratory Syndrome Coronavirus Superspreading Event Involving 81 Persons, Korea 2015",http://dx.doi.org/10.3346/jkms.2015.30.11.1701,PMC4630490,26539018,CC BY-NC,"Since the first imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was reported on May 20, 2015 in Korea, there have been 186 laboratory-confirmed cases of MERS-CoV infection with 36 fatalities. Ninety-seven percent (181/186) of the cases had exposure to the health care facilities. We are reporting a superspreading event that transmitted MERS-CoV to 81 persons at a hospital emergency room (ER) during the Korean outbreak in 2015. The index case was a 35-yr-old man who had vigorous coughing while staying at the ER for 58 hr. As in severe acute respiratory syndrome outbreaks, superspreading events can cause a large outbreak of MERS in healthcare facilities with severe consequences. All healthcare facilities should establish and implement infection prevention and control measure as well as triage policies and procedures for early detection and isolation of suspected MERS-CoV cases.",2015 Nov 16,"['Oh, Myoung-don', 'Choe, Pyoeng Gyun', 'Oh, Hong Sang', 'Park, Wan Beom', 'Lee, Sang-Min', 'Park, Jinkyeong', 'Lee, Sang Kook', 'Song, Jeong-Sup', 'Kim, Nam Joong']",J Korean Med Sci,,,True
4e9acd476a5b8224baf48582bd4f4c095feafe27,PMC,Infection with Middle East respiratory syndrome coronavirus.,,PMC4631129,26566382,CC BY-NC,,2015 Autumn,"['Alsolamy, Sami', 'Arabi, Yaseen M']",Can J Respir Ther,,,True
1ce2ec3b5d92a3f2ace27a00bde0165ba6761aa0,PMC,Interval Between Infections and Viral Hierarchy Are Determinants of Viral Interference Following Influenza Virus Infection in a Ferret Model,http://dx.doi.org/10.1093/infdis/jiv260,PMC4633756,25943206,CC BY-NC-ND,"Background. Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. Methods. Ferrets were first infected then challenged 1–14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. Results. Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was <1 week. This effect was virus specific and occurred between antigenically related and unrelated viruses. Coinfections occurred when 1 or 3 days separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Conclusions. The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season.",2015 Dec 1,"['Laurie, Karen L.', 'Guarnaccia, Teagan A.', 'Carolan, Louise A.', 'Yan, Ada W. C.', 'Aban, Malet', 'Petrie, Stephen', 'Cao, Pengxing', 'Heffernan, Jane M.', 'McVernon, Jodie', 'Mosse, Jennifer', 'Kelso, Anne', 'McCaw, James M.', 'Barr, Ian G.']",J Infect Dis,,,True
00f236f9d1a8efc31af9b825e82c6404f5609125,PMC,Interval Between Infections and Viral Hierarchy Are Determinants of Viral Interference Following Influenza Virus Infection in a Ferret Model,http://dx.doi.org/10.1093/infdis/jiv260,PMC4633756,25943206,CC BY-NC-ND,"Background. Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. Methods. Ferrets were first infected then challenged 1–14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. Results. Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was <1 week. This effect was virus specific and occurred between antigenically related and unrelated viruses. Coinfections occurred when 1 or 3 days separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Conclusions. The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season.",2015 Dec 1,"['Laurie, Karen L.', 'Guarnaccia, Teagan A.', 'Carolan, Louise A.', 'Yan, Ada W. C.', 'Aban, Malet', 'Petrie, Stephen', 'Cao, Pengxing', 'Heffernan, Jane M.', 'McVernon, Jodie', 'Mosse, Jennifer', 'Kelso, Anne', 'McCaw, James M.', 'Barr, Ian G.']",J Infect Dis,,,False
5b7753b6a659e6afa0a46fe171a372e682b07010,PMC,Frequent Asymptomatic Respiratory Syncytial Virus Infections During an Epidemic in a Rural Kenyan Household Cohort,http://dx.doi.org/10.1093/infdis/jiv263,PMC4633757,25941331,CC BY-NC-ND,"Background. The characteristics, determinants, and potential contribution to transmission of asymptomatic cases of respiratory syncytial virus (RSV) infection have not been well described. Methods. A cohort of 47 households (493 individuals) in coastal Kenya was recruited and followed for a 26-week period spanning a complete RSV season. Nasopharyngeal swab specimens were requested weekly, during the first 4 weeks, and twice weekly thereafter from all household members, regardless of illness status. The samples were screened for a range of respiratory viruses by multiplex real-time polymerase chain reaction. Results. Tests on 16 928 samples yielded 205 RSV infection episodes in 179 individuals (37.1%) from 40 different households. Eighty-six episodes (42.0%) were asymptomatic. Factors independently associated with an increased risk of asymptomatic RSV infection episodes were higher age, shorter duration of infection, bigger household size, lower peak viral load, absence of concurrent RSV infections within the household, infection by RSV group B, and no prior human rhinovirus infections. The propensity of RSV spread in households was dependent on symptom status and amount (duration and load) of virus shed. Conclusions. While asymptomatic RSV was less likely to spread, the high frequency of symptomless RSV infection episodes highlights a potentially important role of asymptomatic infections in the community transmission of RSV.",2015 Dec 1,"['Munywoki, Patrick K.', 'Koech, Dorothy C.', 'Agoti, Charles N.', 'Bett, Ann', 'Cane, Patricia A.', 'Medley, Graham F.', 'Nokes, D. James']",J Infect Dis,,,True
26e505b0228a95ae17d9dfee8ce18ff2af4ddb0c,PMC,Recombinant Receptor Binding Domain Protein Induces Partial Protective Immunity in Rhesus Macaques Against Middle East Respiratory Syndrome Coronavirus Challenge(),http://dx.doi.org/10.1016/j.ebiom.2015.08.031,PMC4634622,26629538,CC BY-NC-ND,"BACKGROUND: Development an effective vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) is urgent and limited information is available on vaccination in nonhuman primate (NHP) model. We herein report of evaluating a recombinant receptor-binding domain (rRBD) protein vaccine in a rhesus macaque model. METHODS: Nine monkeys were randomly assigned to high-dose, low-dose and mock groups,which were immunized with different doses of rRBD plus alum adjuvant or adjuvant alone at different time points (0, 8, 25 weeks). Immunological analysis was conducted after each immunisation. Monkeys were challenged with MERS-CoV at 14 days after the final immunisation followed by observation for clinical signs and chest X-rays. Nasal, oropharyngeal and rectal swabs were also collected for analyses. Monkeys were euthanized 3 days after challenge and multiple specimens from tissues were collected for pathological, virological and immunological tests. CONCLUSION: Robust and sustained immunological responses (including neutralisation antibody) were elicited by the rRBD vaccination. Besides, rRBD vaccination alleviated pneumonia with evidence of reduced tissue impairment and clinical manifestation in monkeys. Furthermore, the rRBD vaccine decreased viral load of lung, trachea and oropharyngeal swabs of monkeys. These data in NHP paves a way for further development of an effective human vaccine against MERS-CoV infection.",2015 Aug 18,"['Lan, Jiaming', 'Yao, Yanfeng', 'Deng, Yao', 'Chen, Hong', 'Lu, Guangwen', 'Wang, Wen', 'Bao, Linlin', 'Deng, Wei', 'Wei, Qiang', 'Gao, George F.', 'Qin, Chuan', 'Tan, Wenjie']",EBioMedicine,,,False
5ba2228dbf968996a9e05910fb0126e1851b89a8,PMC,"MERS Vaccine Candidate Offers Promise, but Questions Remain",http://dx.doi.org/10.1016/j.ebiom.2015.09.037,PMC4634784,26629514,CC BY-NC-ND,,2015 Sep 25,"Menachery, Vineet D.",EBioMedicine,,,False
d1f8d3907931e02487816f3a62224659d65f872e,PMC,The Return of Lombroso? Ethical Aspects of (Visions of) Preventive Forensic Screening,http://dx.doi.org/10.1093/phe/phu048,PMC4638059,26566397,CC BY-NC,"The vision of legendary criminologist Cesare Lombroso to use scientific theories of individual causes of crime as a basis for screening and prevention programmes targeting individuals at risk for future criminal behaviour has resurfaced, following advances in genetics, neuroscience and psychiatric epidemiology. This article analyses this idea and maps its ethical implications from a public health ethical standpoint. Twenty-seven variants of the new Lombrosian vision of forensic screening and prevention are distinguished, and some scientific and technical limitations are noted. Some lures, biases and structural factors, making the application of the Lombrosian idea likely in spite of weak evidence are pointed out and noted as a specific type of ethical aspect. Many classic and complex ethical challenges for health screening programmes are shown to apply to the identified variants and the choice between them, albeit with peculiar and often provoking variations. These variations are shown to actualize an underlying theoretical conundrum in need of further study, pertaining to the relationship between public health ethics and the ethics and values of criminal law policy.",2015 Nov 28,"['Munthe, Christian', 'Radovic, Susanna']",Public Health Ethics,,,True
75fbdec55c05102f8337e48dda0c8b6cf27dac52,PMC,Alteration of somatostatin receptor 2 expression in canine mammary gland tumor,http://dx.doi.org/10.1292/jvms.15-0002,PMC4638304,25985817,CC BY-NC-ND,"Somatostatin receptor 2 (SSTR2) is a negative regulator of cell proliferation in human breast cancer. Since there is little information about SSTR2 in canine mammary gland tumor (MGT), we clarified its distribution and expression level in normal mammary gland, benign MGT and malignant MGT. SSTR2 expression determined by immunohistochemical staining was observed in the cytoplasm of luminal epithelial cells. The intensity was negatively correlated with malignancy: normal tissues and some of the benign tumors had the highest levels, while the malignant tumors had little or no SSTR2 expression. As for the Western blotting, SSTR2 protein level in benign tumors was significantly lower than the normal mammary gland. On the other hand, SSTR2 protein levels in two of three malignant tumors were higher than the other groups. These results suggest that SSTR2 expression alters according to the malignancy of canine MGT.",2015 Oct 18,"['SAKAI, Kosei', 'YONEZAWA, Tomohiro', 'YAMAWAKI, Hideyuki', 'OYAMADA, Toshifumi']",J Vet Med Sci,,,True
f5f49c96623a02ef068134f9f468602f5e4763f4,PMC,Alteration of somatostatin receptor 2 expression in canine mammary gland tumor,http://dx.doi.org/10.1292/jvms.15-0002,PMC4638304,25985817,CC BY-NC-ND,"Somatostatin receptor 2 (SSTR2) is a negative regulator of cell proliferation in human breast cancer. Since there is little information about SSTR2 in canine mammary gland tumor (MGT), we clarified its distribution and expression level in normal mammary gland, benign MGT and malignant MGT. SSTR2 expression determined by immunohistochemical staining was observed in the cytoplasm of luminal epithelial cells. The intensity was negatively correlated with malignancy: normal tissues and some of the benign tumors had the highest levels, while the malignant tumors had little or no SSTR2 expression. As for the Western blotting, SSTR2 protein level in benign tumors was significantly lower than the normal mammary gland. On the other hand, SSTR2 protein levels in two of three malignant tumors were higher than the other groups. These results suggest that SSTR2 expression alters according to the malignancy of canine MGT.",2015 Oct 18,"['SAKAI, Kosei', 'YONEZAWA, Tomohiro', 'YAMAWAKI, Hideyuki', 'OYAMADA, Toshifumi']",J Vet Med Sci,,,False
f601587d47e1c6f922247d571299bb21624ac0da,PMC,A phylogenomic data-driven exploration of viral origins and evolution,http://dx.doi.org/10.1126/sciadv.1500527,PMC4643759,26601271,CC BY-NC,"The origin of viruses remains mysterious because of their diverse and patchy molecular and functional makeup. Although numerous hypotheses have attempted to explain viral origins, none is backed by substantive data. We take full advantage of the wealth of available protein structural and functional data to explore the evolution of the proteomic makeup of thousands of cells and viruses. Despite the extremely reduced nature of viral proteomes, we established an ancient origin of the “viral supergroup” and the existence of widespread episodes of horizontal transfer of genetic information. Viruses harboring different replicon types and infecting distantly related hosts shared many metabolic and informational protein structural domains of ancient origin that were also widespread in cellular proteomes. Phylogenomic analysis uncovered a universal tree of life and revealed that modern viruses reduced from multiple ancient cells that harbored segmented RNA genomes and coexisted with the ancestors of modern cells. The model for the origin and evolution of viruses and cells is backed by strong genomic and structural evidence and can be reconciled with existing models of viral evolution if one considers viruses to have originated from ancient cells and not from modern counterparts.",2015 Sep 25,"['Nasir, Arshan', 'Caetano-Anollés, Gustavo']",Sci Adv,,,True
b76b1127689c03ddc50a70b8dc0057dac74fb805,PMC,A nine-month-old girl with respiratory failure and rhomboencephalitis,,PMC4644002,26600807,CC BY-NC,,2015 Sep-Oct,"['Foo, Cheryl PZ', 'McDermid, Andrew', 'Grudeski, Elsie', 'Booth, Tim F', 'Bullard, Jared']",Can J Infect Dis Med Microbiol,,,True
3bb1bf62e09f90f586662be381ca7660090400a8,PMC,Viral Polymerase-Helicase Complexes Regulate Replication Fidelity To Overcome Intracellular Nucleotide Depletion,http://dx.doi.org/10.1128/JVI.01553-15,PMC4645662,26311883,CC BY-NC-SA,"To date, the majority of work on RNA virus replication fidelity has focused on the viral RNA polymerase, while the potential role of other viral replicase proteins in this process is poorly understood. Previous studies used resistance to broad-spectrum RNA mutagens, such as ribavirin, to identify polymerases with increased fidelity that avoid misincorporation of such base analogues. We identified a novel variant in the alphavirus viral helicase/protease, nonstructural protein 2 (nsP2) that operates in concert with the viral polymerase nsP4 to further alter replication complex fidelity, a functional linkage that was conserved among the alphavirus genus. Purified chikungunya virus nsP2 presented delayed helicase activity of the high-fidelity enzyme, and yet purified replication complexes manifested stronger RNA polymerization kinetics. Because mutagenic nucleoside analogs such as ribavirin also affect intracellular nucleotide pools, we addressed the link between nucleotide depletion and replication fidelity by using purine and pyrimidine biosynthesis inhibitors. High-fidelity viruses were more resistant to these conditions, and viral growth could be rescued by the addition of exogenous nucleosides, suggesting that mutagenesis by base analogues requires nucleotide pool depletion. This study describes a novel function for nsP2, highlighting the role of other components of the replication complex in regulating viral replication fidelity, and suggests that viruses can alter their replication complex fidelity to overcome intracellular nucleotide-depleting conditions. IMPORTANCE Previous studies using the RNA mutagen ribavirin to select for drug-resistant variants have highlighted the essential role of the viral RNA-dependent RNA polymerase in regulating replication fidelity. However, the role of other viral replicase components in replication fidelity has not been studied in detail. We identified here an RNA mutagen-resistant variant of the nsP2 helicase/protease that conferred increased fidelity and yet could not operate in the same manner as high-fidelity polymerases. We show that the alphavirus helicase is a key component of the fidelity-regulating machinery. Our data show that the RNA mutagenic activity of compounds such as ribavirin is coupled to and potentiated by nucleotide depletion and that RNA viruses can fine-tune their replication fidelity when faced with an intracellular environment depleted of nucleotides.",2015 Aug 26,"['Stapleford, Kenneth A.', 'Rozen-Gagnon, Kathryn', 'Das, Pratyush Kumar', 'Saul, Sirle', 'Poirier, Enzo Z.', 'Blanc, Hervé', 'Vidalain, Pierre-Olivier', 'Merits, Andres', 'Vignuzzi, Marco']",J Virol,,,True
3920596af370a9e2e4c31d89444c980ceadbc4f8,PMC,A design principle for a single-stranded RNA genome that replicates with less double-strand formation,http://dx.doi.org/10.1093/nar/gkv742,PMC4652763,26202975,CC BY-NC,"Single-stranded RNA (ssRNA) is the simplest form of genetic molecule and constitutes the genome in some viruses and presumably in primitive life-forms. However, an innate and unsolved problem regarding the ssRNA genome is formation of inactive double-stranded RNA (dsRNA) during replication. Here, we addressed this problem by focusing on the secondary structure. We systematically designed RNAs with various structures and observed dsRNA formation during replication using an RNA replicase (Qβ replicase). From the results, we extracted a simple rule regarding ssRNA genome replication with less dsRNA formation (less GC number in loops) and then designed an artificial RNA that encodes a domain of the β-galactosidase gene based on this rule. We also obtained evidence that this rule governs the natural genomes of all bacterial and most fungal viruses presently known. This study revealed one of the structural design principles of an ssRNA genome that replicates continuously with less dsRNA formation.",2015 Sep 18,"['Usui, Kimihito', 'Ichihashi, Norikazu', 'Yomo, Tetsuya']",Nucleic Acids Res,,,True
c1f6fc9f26417df40a63350abb544265516ccad1,PMC,A design principle for a single-stranded RNA genome that replicates with less double-strand formation,http://dx.doi.org/10.1093/nar/gkv742,PMC4652763,26202975,CC BY-NC,"Single-stranded RNA (ssRNA) is the simplest form of genetic molecule and constitutes the genome in some viruses and presumably in primitive life-forms. However, an innate and unsolved problem regarding the ssRNA genome is formation of inactive double-stranded RNA (dsRNA) during replication. Here, we addressed this problem by focusing on the secondary structure. We systematically designed RNAs with various structures and observed dsRNA formation during replication using an RNA replicase (Qβ replicase). From the results, we extracted a simple rule regarding ssRNA genome replication with less dsRNA formation (less GC number in loops) and then designed an artificial RNA that encodes a domain of the β-galactosidase gene based on this rule. We also obtained evidence that this rule governs the natural genomes of all bacterial and most fungal viruses presently known. This study revealed one of the structural design principles of an ssRNA genome that replicates continuously with less dsRNA formation.",2015 Sep 18,"['Usui, Kimihito', 'Ichihashi, Norikazu', 'Yomo, Tetsuya']",Nucleic Acids Res,,,False
3677789674e47d9e9b35f87c659430e5295370e9,PMC,Human Coronavirus 229E Remains Infectious on Common Touch Surface Materials,http://dx.doi.org/10.1128/mBio.01697-15,PMC4659470,26556276,CC BY-NC-SA,"The evolution of new and reemerging historic virulent strains of respiratory viruses from animal reservoirs is a significant threat to human health. Inefficient human-to-human transmission of zoonotic strains may initially limit the spread of transmission, but an infection may be contracted by touching contaminated surfaces. Enveloped viruses are often susceptible to environmental stresses, but the human coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have recently caused increasing concern of contact transmission during outbreaks. We report here that pathogenic human coronavirus 229E remained infectious in a human lung cell culture model following at least 5 days of persistence on a range of common nonbiocidal surface materials, including polytetrafluoroethylene (Teflon; PTFE), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. We have shown previously that noroviruses are destroyed on copper alloy surfaces. In this new study, human coronavirus 229E was rapidly inactivated on a range of copper alloys (within a few minutes for simulated fingertip contamination) and Cu/Zn brasses were very effective at lower copper concentration. Exposure to copper destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes. Cu(I) and Cu(II) moieties were responsible for the inactivation, which was enhanced by reactive oxygen species generation on alloy surfaces, resulting in even faster inactivation than was seen with nonenveloped viruses on copper. Consequently, copper alloy surfaces could be employed in communal areas and at any mass gatherings to help reduce transmission of respiratory viruses from contaminated surfaces and protect the public health.",2015 Nov 10,"['Warnes, Sarah L.', 'Little, Zoë R.', 'Keevil, C. William']",mBio,,,True
03a9a21fad1427fc2dbb6a4969627d0a76459597,PMC,Prerequisites for Effective Implementation of Telemedicine: Focusing on Current Situations in Korea,http://dx.doi.org/10.4258/hir.2015.21.4.251,PMC4659882,26618031,CC BY-NC,"OBJECTIVES: The practice of telemedicine requires social interventions and systems for efficient implementation. Further, it requires sufficient discussions among related parties because the purpose of telemedicine is diagnosis and treatment, and the participation of medical specialists is essential. Based on the characteristics of the healthcare structure of Korea, which has a low proportion of public healthcare and most patients are taken care of by a few large tertiary care hospitals, the fundamental issues need to be discussed. METHODS: A comparison was conducted with overseas cases to discuss the prerequisites for the effective implementation of telemedicine in South Korea under the current situation. We also examined the structural characteristics of the Korean medical community. RESULTS: The current paper recommends that an in-depth analysis and studies are conducted on the following aspects: a search for telemedicine services focused on public healthcare, a search of services for illnesses that impose high levels of burden on households, and the development and implementation of a telemedicine system for follow-up management at primary and secondary care hospitals after the patient undergoes surgery or treatment at tertiary care hospitals. CONCLUSIONS: As the technology develops, the focus should also be on factors such as safety, usefulness, availability, and how the functions will be realized in order to enable user communication. A clear system should be established to regulate and manage the lack of sufficient discussions. In addition, seeking projects and systems that reflect the characteristics of each country will facilitate the efficient implementation of telemedicine.",2015 Oct 31,"['Lee, Hyeoi-Yun', 'Lee, Ji-San', 'Kim, Jeongeun']",Healthc Inform Res,,,True
13bcbfda70f3fae9fc63e5a041e4f3dba700b95c,PMC,Why should cell biologists study microbial pathogens?,http://dx.doi.org/10.1091/mbc.E15-03-0144,PMC4666125,26628749,CC BY-NC-SA,"One quarter of all deaths worldwide each year result from infectious diseases caused by microbial pathogens. Pathogens infect and cause disease by producing virulence factors that target host cell molecules. Studying how virulence factors target host cells has revealed fundamental principles of cell biology. These include important advances in our understanding of the cytoskeleton, organelles and membrane-trafficking intermediates, signal transduction pathways, cell cycle regulators, the organelle/protein recycling machinery, and cell-death pathways. Such studies have also revealed cellular pathways crucial for the immune response. Discoveries from basic research on the cell biology of pathogenesis are actively being translated into the development of host-targeted therapies to treat infectious diseases. Thus there are many reasons for cell biologists to incorporate the study of microbial pathogens into their research programs.",2015 Dec 1,"Welch, Matthew D.",Mol Biol Cell,,,True
d8b7b5e4c3daa4fc5444223319456deecad9acfb,PMC,TRIM21: a cytosolic Fc receptor with broad antibody isotype specificity,http://dx.doi.org/10.1111/imr.12363,PMC4670481,26497531,CC BY-NC-ND,"Antibodies are key molecules in the fight against infections. Although previously thought to mediate protection solely in the extracellular environment, recent research has revealed that antibody-mediated protection extends to the cytosolic compartment of cells. This postentry viral defense mechanism requires binding of the antibody to a cytosolic Fc receptor named tripartite motif containing 21 (TRIM21). In contrast to other Fc receptors, TRIM21 shows remarkably broad isotype specificity as it does not only bind IgG but also IgM and IgA. When viral pathogens coated with these antibody isotypes enter the cytosol, TRIM21 is rapidly recruited and efficient neutralization occurs before the virus has had the time to replicate. In addition, inflammatory signaling is induced. As such, TRIM21 acts as a cytosolic sensor that engages antibodies that have failed to protect against infection in the extracellular environment. Here, we summarize our current understanding of how TRIM21 orchestrates humoral immunity in the cytosolic environment.",2015 Nov 26,"['Foss, Stian', 'Watkinson, Ruth', 'Sandlie, Inger', 'James, Leo C', 'Andersen, Jan Terje']",Immunol Rev,,,True
9c200d5d5797bb4162316b729636023f3fade4c9,PMC,Ramsay Hunt syndrome and zoster laryngitis with multiple cranial nerve involvement,http://dx.doi.org/10.1016/j.idcr.2015.02.003,PMC4672621,26793453,CC BY-NC-ND,"Ramsay Hunt syndrome is characterized by varicella zoster virus infection affecting the geniculate ganglion of the facial nerve. It typically presents with vesicles in the external auditory canal associated with auricular pain and peripheral facial nerve paralysis. Although vestibulocochlear nerve is frequently co-involved during the course of Ramsay Hunt syndrome, multiple lower cranial nerve involvement has rarely been described in the literature. In addition, laryngitis due to varicella zoster virus is a diagnostic challenge due to its unfamiliarity among clinicians. We report a case of Ramsay Hunt syndrome with laryngitis involving multiple lower cranial nerves.",2015 Mar 20,"['Shinha, Takashi', 'Krishna, Pasala']",IDCases,,,False
9b2f83db4c307ae17c146bb6625ddb01474bbd9a,PMC,Fc receptors and their influence on efficacy of therapeutic antibodies for treatment of viral diseases,http://dx.doi.org/10.1586/14787210.2015.1079127,PMC4673539,26466016,CC BY-NC-ND,"The lack of vaccines against several important viral diseases necessitates the development of therapeutics to save lives and control epidemics. In recent years, therapeutic antibodies have received considerable attention due to their good safety profiles and clinical success when used against viruses such as respiratory syncytial virus, Ebola virus and Hendra virus. The binding affinity of these antibodies can directly impact their therapeutic efficacy. However, we and others have also demonstrated that the subtype of Fc-gamma receptors (FcγRs) engaged influences the stoichiometric requirement for virus neutralization. Hence, the development of therapeutic antibodies against infectious diseases should consider the FcγRs engaged and Fc-effector functions involved. This review highlights the current state of knowledge about FcγRs and FcγR effector functions involved in virus neutralization, with emphasis on factors that can affect FcγR engagement. A better understanding of Fc-FcγR interactions during virus neutralization will allow development of therapeutic antibodies that are efficacious and can be administered with minimal side effects.",2015 Nov 2,"['Chan, Kuan Rong', 'Ong, Eugenia Z', 'Mok, Darren ZL', 'Ooi, Eng Eong']",Expert Rev Anti Infect Ther,,,True
bf56dbf1f0c9734d135d18b33d9b7476b53d14a6,PMC,Implementation of Quaternary Prevention in the Korean Healthcare System: Lessons From the 2015 Middle East Respiratory Syndrome Coronavirus Outbreak in the Republic of Korea,http://dx.doi.org/10.3961/jpmph.15.059,PMC4676639,26639739,CC BY-NC,"Quaternary prevention should be implemented to minimize harm to patients because the ultimate goal of medicine is to prevent disease and promote health. Primary care physicians have a major responsibility in quaternary prevention, and the establishment of clinical epidemiology as a distinct field of study would create a role charged with minimizing patient harm arising from over-medicalization.",2015 Nov 24,"Bae, Jong-Myon",J Prev Med Public Health,,,True
ebc7bbdf4d1954bd8575aa830977118cc1990759,PMC,Current Status of Infection Prevention and Control Programs for Emergency Medical Personnel in the Republic of Korea,http://dx.doi.org/10.3961/jpmph.15.058,PMC4676640,26639747,CC BY-NC,"OBJECTIVES: Emergency medical personnel (EMPs) are pre-hospital emergency responders who are at risk of exposure to infections and may also serve as a source for the transmission of infections. However, few studies of infection control have specifically addressed EMPs in the Republic of Korea (hereafter Korea). The goal of this study was to assess the current status of infection prevention and control programs (IPCPs) for EMPs in Korea. METHODS: A cross-sectional survey was conducted to quantitatively assess the resources and activities of IPCPs. A total of 907 EMPs in five metropolitan cities completed a structured questionnaire from September 2014 to January 2015. The data were analyzed using descriptive statistics, multi-response analysis, and the chi-square test. RESULTS: The mean age of the participants was 34.8±15.1 years. IPCPs were found to have weaknesses with regard to the following resources: the assignment of infection control personnel (ICP) (79.5%), hand hygiene resources such as waterless antiseptics (79.3%), the use of paper towels (38.9%), personal protective equipment such as face shields (46.9%), and safety containers for sharps and a separated space for the disposal of infectious waste (10.1%). Likewise, the following activities were found to be inadequately incorporated into the workflow of EMPs: education about infection control (77.5%), post-exposure management (35.9%), and the decontamination of items and spaces after use (88.4%). ICP were found to have a significant effect on the resources and activities of IPCPs (p<0.001). The resources and activities of IPCPs were found to be significantly different among the five cities (p<0.001). CONCLUSIONS: IPCPs for EMPs showed some limitations in their resources and activities. IPCPs should be actively supported, and specific IPCP activities for EMPs should be developed.",2015 Nov 25,"['Oh, Hyang Soon', 'Uhm, Dong Choon']",J Prev Med Public Health,,,True
334218adcdcab21a5eec6c83abdd2f9267472481,PMC,Current Status of Infection Prevention and Control Programs for Emergency Medical Personnel in the Republic of Korea,http://dx.doi.org/10.3961/jpmph.15.058,PMC4676640,26639747,CC BY-NC,"OBJECTIVES: Emergency medical personnel (EMPs) are pre-hospital emergency responders who are at risk of exposure to infections and may also serve as a source for the transmission of infections. However, few studies of infection control have specifically addressed EMPs in the Republic of Korea (hereafter Korea). The goal of this study was to assess the current status of infection prevention and control programs (IPCPs) for EMPs in Korea. METHODS: A cross-sectional survey was conducted to quantitatively assess the resources and activities of IPCPs. A total of 907 EMPs in five metropolitan cities completed a structured questionnaire from September 2014 to January 2015. The data were analyzed using descriptive statistics, multi-response analysis, and the chi-square test. RESULTS: The mean age of the participants was 34.8±15.1 years. IPCPs were found to have weaknesses with regard to the following resources: the assignment of infection control personnel (ICP) (79.5%), hand hygiene resources such as waterless antiseptics (79.3%), the use of paper towels (38.9%), personal protective equipment such as face shields (46.9%), and safety containers for sharps and a separated space for the disposal of infectious waste (10.1%). Likewise, the following activities were found to be inadequately incorporated into the workflow of EMPs: education about infection control (77.5%), post-exposure management (35.9%), and the decontamination of items and spaces after use (88.4%). ICP were found to have a significant effect on the resources and activities of IPCPs (p<0.001). The resources and activities of IPCPs were found to be significantly different among the five cities (p<0.001). CONCLUSIONS: IPCPs for EMPs showed some limitations in their resources and activities. IPCPs should be actively supported, and specific IPCP activities for EMPs should be developed.",2015 Nov 25,"['Oh, Hyang Soon', 'Uhm, Dong Choon']",J Prev Med Public Health,,,False
949bc6088e216b0ad1e76e3792dc402a5eaf47ab,PMC,Current Status of Infection Prevention and Control Programs for Emergency Medical Personnel in the Republic of Korea,http://dx.doi.org/10.3961/jpmph.15.058,PMC4676640,26639747,CC BY-NC,"OBJECTIVES: Emergency medical personnel (EMPs) are pre-hospital emergency responders who are at risk of exposure to infections and may also serve as a source for the transmission of infections. However, few studies of infection control have specifically addressed EMPs in the Republic of Korea (hereafter Korea). The goal of this study was to assess the current status of infection prevention and control programs (IPCPs) for EMPs in Korea. METHODS: A cross-sectional survey was conducted to quantitatively assess the resources and activities of IPCPs. A total of 907 EMPs in five metropolitan cities completed a structured questionnaire from September 2014 to January 2015. The data were analyzed using descriptive statistics, multi-response analysis, and the chi-square test. RESULTS: The mean age of the participants was 34.8±15.1 years. IPCPs were found to have weaknesses with regard to the following resources: the assignment of infection control personnel (ICP) (79.5%), hand hygiene resources such as waterless antiseptics (79.3%), the use of paper towels (38.9%), personal protective equipment such as face shields (46.9%), and safety containers for sharps and a separated space for the disposal of infectious waste (10.1%). Likewise, the following activities were found to be inadequately incorporated into the workflow of EMPs: education about infection control (77.5%), post-exposure management (35.9%), and the decontamination of items and spaces after use (88.4%). ICP were found to have a significant effect on the resources and activities of IPCPs (p<0.001). The resources and activities of IPCPs were found to be significantly different among the five cities (p<0.001). CONCLUSIONS: IPCPs for EMPs showed some limitations in their resources and activities. IPCPs should be actively supported, and specific IPCP activities for EMPs should be developed.",2015 Nov 25,"['Oh, Hyang Soon', 'Uhm, Dong Choon']",J Prev Med Public Health,,,False
9a073155468db6b596080b5b78323d6caeeb6d68,PMC,Current Status of Infection Prevention and Control Programs for Emergency Medical Personnel in the Republic of Korea,http://dx.doi.org/10.3961/jpmph.15.058,PMC4676640,26639747,CC BY-NC,"OBJECTIVES: Emergency medical personnel (EMPs) are pre-hospital emergency responders who are at risk of exposure to infections and may also serve as a source for the transmission of infections. However, few studies of infection control have specifically addressed EMPs in the Republic of Korea (hereafter Korea). The goal of this study was to assess the current status of infection prevention and control programs (IPCPs) for EMPs in Korea. METHODS: A cross-sectional survey was conducted to quantitatively assess the resources and activities of IPCPs. A total of 907 EMPs in five metropolitan cities completed a structured questionnaire from September 2014 to January 2015. The data were analyzed using descriptive statistics, multi-response analysis, and the chi-square test. RESULTS: The mean age of the participants was 34.8±15.1 years. IPCPs were found to have weaknesses with regard to the following resources: the assignment of infection control personnel (ICP) (79.5%), hand hygiene resources such as waterless antiseptics (79.3%), the use of paper towels (38.9%), personal protective equipment such as face shields (46.9%), and safety containers for sharps and a separated space for the disposal of infectious waste (10.1%). Likewise, the following activities were found to be inadequately incorporated into the workflow of EMPs: education about infection control (77.5%), post-exposure management (35.9%), and the decontamination of items and spaces after use (88.4%). ICP were found to have a significant effect on the resources and activities of IPCPs (p<0.001). The resources and activities of IPCPs were found to be significantly different among the five cities (p<0.001). CONCLUSIONS: IPCPs for EMPs showed some limitations in their resources and activities. IPCPs should be actively supported, and specific IPCP activities for EMPs should be developed.",2015 Nov 25,"['Oh, Hyang Soon', 'Uhm, Dong Choon']",J Prev Med Public Health,,,False
cec09e3b5beea8a13cd359b3aa53e5ee0d40b969,PMC,A New Measure for Assessing the Public Health Response to a Middle East Respiratory Syndrome Coronavirus Outbreak,http://dx.doi.org/10.3961/jpmph.15.069,PMC4676641,26639741,CC BY-NC,"Contact monitoring is an essential component of the public health response to a Middle East respiratory syndrome coronavirus outbreak, and is required for an effective quarantine to contain the epidemic. The timeliness of a quarantine is associated with its effectiveness. This paper provides a conceptual framework to describe the process of contact monitoring, and proposes a new measure called the “timely quarantined proportion” as a tool to assess the adequacy of a public health response.",2015 Nov 30,"Cho, Sung-il",J Prev Med Public Health,,,True
e1b312167d5ea6a1ed3c071b05b7bd0a48a975df,PMC,Structural Factors of the Middle East Respiratory Syndrome Coronavirus Outbreak as a Public Health Crisis in Korea and Future Response Strategies,http://dx.doi.org/10.3961/jpmph.15.066,PMC4676643,26639738,CC BY-NC,"The recent Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak has originated from a failure in the national quarantine system in the Republic of Korea as most basic role of protecting the safety and lives of its citizens. Furthermore, a number of the Korean healthcare system’s weaknesses seem to have been completely exposed. The MERS-CoV outbreak can be considered a typical public health crisis in that the public was not only greatly terrorized by the actual fear of the disease, but also experienced a great impact to their daily lives, all in a short period of time. Preparedness for and an appropriate response to a public health crisis require comprehensive systematic public healthcare measures to address risks comprehensively with an all-hazards approach. Consequently, discussion regarding establishment of post-MERS-CoV improvement measures must focus on the total reform of the national quarantine system and strengthening of the public health infrastructure. In addition, the Korea Centers for Disease Control and Prevention must implement specific strategies of action including taking on the role of “control tower” in a public health emergency, training of Field Epidemic Intelligence Service officers, establishment of collaborative governance between central and local governments for infection prevention and control, strengthening the roles and capabilities of community-based public hospitals, and development of nationwide crisis communication methods.",2015 Nov 30,"Kim, Dong-Hyun",J Prev Med Public Health,,,True
2c70242370bc27a555b206e5bd62b68f1edb772d,PMC,Costly Lessons From the 2015 Middle East Respiratory Syndrome Coronavirus Outbreak in Korea,http://dx.doi.org/10.3961/jpmph.15.064,PMC4676647,26639740,CC BY-NC,"Since the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea (hereafter Korea) began on May 11, 2015, a total of 186 persons have been infected by the MERS coronavirus, 38 of whom have died. With this number, Korea becomes second only to the Kingdom of Saudi Arabia in the ranking of cumulative MERS cases. In this paper Korea’s unique experience of an outbreak of MERS will be summarized and discussed briefly.",2015 Nov 25,"Lee, Sang-il",J Prev Med Public Health,,,True
53f9b02ce4cc149507a9d402dcf9d4c191b3bb29,PMC,Identification of potential drug targets by subtractive genome analysis of Escherichia coli O157:H7: an in silico approach,http://dx.doi.org/10.2147/AABC.S88522,PMC4677596,26677339,CC BY-NC,"Bacterial enteric infections resulting in diarrhea, dysentery, or enteric fever constitute a huge public health problem, with more than a billion episodes of disease annually in developing and developed countries. In this study, the deadly agent of hemorrhagic diarrhea and hemolytic uremic syndrome, Escherichia coli O157:H7 was investigated with extensive computational approaches aimed at identifying novel and broad-spectrum antibiotic targets. A systematic in silico workflow consisting of comparative genomics, metabolic pathways analysis, and additional drug prioritizing parameters was used to identify novel drug targets that were essential for the pathogen’s survival but absent in its human host. Comparative genomic analysis of Kyoto Encyclopedia of Genes and Genomes annotated metabolic pathways identified 350 putative target proteins in E. coli O157:H7 which showed no similarity to human proteins. Further bio-informatic approaches including prediction of subcellular localization, calculation of molecular weight, and web-based investigation of 3D structural characteristics greatly aided in filtering the potential drug targets from 350 to 120. Ultimately, 44 non-homologous essential proteins of E. coli O157:H7 were prioritized and proved to have the eligibility to become novel broad-spectrum antibiotic targets and DNA polymerase III alpha (dnaE) was the top-ranked among these targets. Moreover, druggability of each of the identified drug targets was evaluated by the DrugBank database. In addition, 3D structure of the dnaE was modeled and explored further for in silico docking with ligands having potential druggability. Finally, we confirmed that the compounds N-coeleneterazine and N-(1,4-dihydro-5H-tetrazol-5-ylidene)-9-oxo-9H-xanthene-2-sulfon-amide were the most suitable ligands of dnaE and hence proposed as the potential inhibitors of this target protein. The results of this study could facilitate the discovery and release of new and effective drugs against E. coli O157:H7 and other deadly human bacterial pathogens.",2015 Dec 8,"['Mondal, Shakhinur Islam', 'Ferdous, Sabiha', 'Jewel, Nurnabi Azad', 'Akter, Arzuba', 'Mahmud, Zabed', 'Islam, Md Muzahidul', 'Afrin, Tanzila', 'Karim, Nurul']",Adv Appl Bioinform Chem,,,True
b153ef1a7cb22199b3f2e8901d25a93acf2c7570,PMC,The Use of Ebola Convalescent Plasma to Treat Ebola Virus Disease in Resource-Constrained Settings: A Perspective From the Field,http://dx.doi.org/10.1093/cid/civ680,PMC4678103,26261205,CC BY-NC-ND,"The clinical evaluation of convalescent plasma (CP) for the treatment of Ebola virus disease (EVD) in the current outbreak, predominantly affecting Guinea, Sierra Leone, and Liberia, was prioritized by the World Health Organization in September 2014. In each of these countries, nonrandomized comparative clinical trials were initiated. The Ebola-Tx trial in Conakry, Guinea, enrolled 102 patients by 7 July 2015; no severe adverse reactions were noted. The Ebola-CP trial in Sierra Leone and the EVD001 trial in Liberia have included few patients. Although no efficacy data are available yet, current field experience supports the safety, acceptability, and feasibility of CP as EVD treatment. Longer-term follow-up as well as data from nontrial settings and evidence on the scalability of the intervention are required. CP sourced from within the outbreak is the most readily available source of anti-EVD antibodies. Until the advent of effective antivirals or monoclonal antibodies, CP merits further evaluation.",2016 Jan 1,"['van Griensven, Johan', 'De Weiggheleire, Anja', 'Delamou, Alexandre', 'Smith, Peter G.', 'Edwards, Tansy', 'Vandekerckhove, Philippe', 'Bah, Elhadj Ibrahima', 'Colebunders, Robert', 'Herve, Isola', 'Lazaygues, Catherine', 'Haba, Nyankoye', 'Lynen, Lutgarde']",Clin Infect Dis,,,True
87dcbcb15da36050308aca4284d842193d99cd6c,PMC,A Downward Trend of the Ratio of Influenza RNA Copy Number to Infectious Viral Titer in Hospitalized Influenza A-Infected Patients,http://dx.doi.org/10.1093/ofid/ofv166,PMC4680923,26677457,CC BY-NC-ND,"Background. Efficacy endpoints in influenza clinical trials may include clinical symptoms and virological measurements, although virology cannot serve as the primary endpoint. We investigated the relationship between influenza A RNA copy number and quantity of infectious viruses in hospitalized influenza patients. Methods. One hundred fifty influenza-infected, hospitalized patients were included in this prospective cohort study spanning the 2012–2013 influenza season. Daily nasopharyngeal samples were collected during hospitalization, and influenza A RNA copy number and infectious viral titer were monitored. Results. The decay rate for 50% tissue culture infectious dose (TCID(50)) was 0.51 ± 0.14 log(10) TCID(50)/mL per day, whereas the RNA copy number decreased at a rate of 0.41 ± 0.04 log(10) copies/mL per day (n = 433). The log ratio of the RNA copy number to the infectious viral titer within patient changes significantly with −0.25 ± 0.09 units per day (P = .0069). For a 12-day observation period, the decay corresponds to a decline of this ratio of 3 log influenza RNA copies. Conclusions. Influenza RNA copy number in nasal swabs is co-linear with culture, although the rate of decay of cell culture-based viral titers was faster than that observed with molecular methods. The study documented a clear decreasing log ratio of the RNA copy number to the infectious viral titer of the patients over time.",2015 Nov 3,"['Van Wesenbeeck, Liesbeth', ""D'Haese, David"", 'Tolboom, Jeroen', 'Meeuws, Hanne', 'Dwyer, Dominic E.', 'Holmes, Mark', 'Ison, Michael G.', 'Katz, Kevin', 'McGeer, Allison', 'Sadoff, Jerald', 'Weverling, Gerrit Jan', 'Stuyver, Lieven']",Open Forum Infect Dis,,,True
b1eb120cfa12a756cba28ee8d08c63aa748f96a8,PMC,Acute Lung Injury Results from Innate Sensing of Viruses by an ER Stress Pathway,http://dx.doi.org/10.1016/j.celrep.2015.05.012,PMC4682876,26051937,CC BY-NC-ND,"Incursions of new pathogenic viruses into humans from animal reservoirs are occurring with alarming frequency. The molecular underpinnings of immune recognition, host responses, and pathogenesis in this setting are poorly understood. We studied pandemic influenza viruses to determine the mechanism by which increasing glycosylation during evolution of surface proteins facilitates diminished pathogenicity in adapted viruses. ER stress during infection with poorly glycosylated pandemic strains activated the unfolded protein response, leading to inflammation, acute lung injury, and mortality. Seasonal strains or viruses engineered to mimic adapted viruses displaying excess glycans on the hemagglutinin did not cause ER stress, allowing preservation of the lungs and survival. We propose that ER stress resulting from recognition of non-adapted viruses is utilized to discriminate “non-self” at the level of protein processing and to activate immune responses, with unintended consequences on pathogenesis. Understanding this mechanism should improve strategies for treating acute lung injury from zoonotic viral infections.",2015 Jun 16,"['Hrincius, Eike R.', 'Liedmann, Swantje', 'Finkelstein, David', 'Vogel, Peter', 'Gansebom, Shane', 'Samarasinghe, Amali E.', 'You, Dahui', 'Cormier, Stephania A.', 'McCullers, Jonathan A.']",Cell Rep,,,True
1c41bda2cfaff0c759b2dd449d583d4e8ba3f6f9,PMC,Acute Lung Injury Results from Innate Sensing of Viruses by an ER Stress Pathway,http://dx.doi.org/10.1016/j.celrep.2015.05.012,PMC4682876,26051937,CC BY-NC-ND,"Incursions of new pathogenic viruses into humans from animal reservoirs are occurring with alarming frequency. The molecular underpinnings of immune recognition, host responses, and pathogenesis in this setting are poorly understood. We studied pandemic influenza viruses to determine the mechanism by which increasing glycosylation during evolution of surface proteins facilitates diminished pathogenicity in adapted viruses. ER stress during infection with poorly glycosylated pandemic strains activated the unfolded protein response, leading to inflammation, acute lung injury, and mortality. Seasonal strains or viruses engineered to mimic adapted viruses displaying excess glycans on the hemagglutinin did not cause ER stress, allowing preservation of the lungs and survival. We propose that ER stress resulting from recognition of non-adapted viruses is utilized to discriminate “non-self” at the level of protein processing and to activate immune responses, with unintended consequences on pathogenesis. Understanding this mechanism should improve strategies for treating acute lung injury from zoonotic viral infections.",2015 Jun 16,"['Hrincius, Eike R.', 'Liedmann, Swantje', 'Finkelstein, David', 'Vogel, Peter', 'Gansebom, Shane', 'Samarasinghe, Amali E.', 'You, Dahui', 'Cormier, Stephania A.', 'McCullers, Jonathan A.']",Cell Rep,,,False
52e323d1ed2d4a0dfbe4f68d15d20430a33de8bf,PMC,Acute Lung Injury Results from Innate Sensing of Viruses by an ER Stress Pathway,http://dx.doi.org/10.1016/j.celrep.2015.05.012,PMC4682876,26051937,CC BY-NC-ND,"Incursions of new pathogenic viruses into humans from animal reservoirs are occurring with alarming frequency. The molecular underpinnings of immune recognition, host responses, and pathogenesis in this setting are poorly understood. We studied pandemic influenza viruses to determine the mechanism by which increasing glycosylation during evolution of surface proteins facilitates diminished pathogenicity in adapted viruses. ER stress during infection with poorly glycosylated pandemic strains activated the unfolded protein response, leading to inflammation, acute lung injury, and mortality. Seasonal strains or viruses engineered to mimic adapted viruses displaying excess glycans on the hemagglutinin did not cause ER stress, allowing preservation of the lungs and survival. We propose that ER stress resulting from recognition of non-adapted viruses is utilized to discriminate “non-self” at the level of protein processing and to activate immune responses, with unintended consequences on pathogenesis. Understanding this mechanism should improve strategies for treating acute lung injury from zoonotic viral infections.",2015 Jun 16,"['Hrincius, Eike R.', 'Liedmann, Swantje', 'Finkelstein, David', 'Vogel, Peter', 'Gansebom, Shane', 'Samarasinghe, Amali E.', 'You, Dahui', 'Cormier, Stephania A.', 'McCullers, Jonathan A.']",Cell Rep,,,True
4e0773d0ae56a69211b358144a99bbecbad56bac,PMC,Expression of arginase I and inducible nitric oxide synthase in the peripheral blood and lymph nodes of HIV-positive patients,http://dx.doi.org/10.3892/mmr.2015.4601,PMC4686052,26647762,CC BY-NC-ND,"Arginase I (Arg I) and inducible nitric oxide synthase (iNOS) are important in regulating immune functions through their metabolites. Previous studies have revealed that the expression of Arg I is increased and the expression of iNOS is reduced in the serum and peripheral blood mononuclear cells of human immunodeficiency virus (HIV)-infected patients. As one of the most important immune organs and HIV replication sites, whether similar changes are present in the lymph nodes following HIV infection remains to be elucidated. To investigate this, the present study collected lymph node and blood specimens from 52 HIV-infected patients to measure the expression levels of Arg I and iNOS by immunohistochemistry and fluoresence-based flow cytometry. Compared with control subjects without HIV infection, the patients with HIV had significantly higher expression levels of Arg I in the lymph nodes and higher frequencies of Arg I(+) CD4(+) T cells and CD8(+) T cells in the blood and lymph nodes, and these results were contrary the those of iNOS in the corresponding compartments. The expression levels of Arg I in the lymph nodes and blood were negatively associated with peripheral CD4(+) T cell count and positively associated with viral load. However, the expression levels of iNOS in the lymph nodes and blood were positively associated with peripheral CD4(+) T cell count and negatively associated with viral load. These results showed that alterations in the expression levels of Arg I and iNOS in the peripheral T cells and peripheral nodes of HIV infected patients are associated with disease progression in these patients. These results indicate a potential to therapeutic strategy for delaying disease progression through regulating and manipulating the expression levels of Arg I and iNOS in patients infected with HIV.",2016 Jan 23,"['ZHANG, NAICHUN', 'DENG, JIANNING', 'WU, FENGYAO', 'LU, XIANGCHAN', 'HUANG, LEI', 'ZHAO, MIN']",Mol Med Rep,,,True
8ee4731a0d1dabf9a61a177aed392c62ca6fb69b,PMC,Renal Complications and Their Prognosis in Korean Patients with Middle East Respiratory Syndrome-Coronavirus from the Central MERS-CoV Designated Hospital,http://dx.doi.org/10.3346/jkms.2015.30.12.1807,PMC4689825,26713056,CC BY-NC,"Some cases of Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) infection presented renal function impairment after the first MERS-CoV patient died of progressive respiratory and renal failure. Thus, MERS-CoV may include kidney tropism. However, reports about the natural courses of MERS-CoV infection in terms of renal complications are scarce. We examined 30 MERS-CoV patients admitted to National Medical Center, Korea. We conducted a retrospective analysis of the serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urine dipstick tests, urinary protein quantitation (ACR or PCR), and other clinical parameters in all patients. Two consecutive results of more than trace (or 1+) of albumin and blood on dipstick test occurred in 18 (60%) (12 [40%]) and 22 (73.3%) (19 [63.3%]) patients, respectively. Fifteen (50.0%) patients showed a random urine ACR or PCR more than 100 mg/g Cr. Eight (26.7%) patients showed acute kidney injury (AKI), and the mean and median durations to the occurrence of AKI from symptom onset were 18 and 16 days, respectively. Old age was associated with a higher occurrence of AKI in the univariate analysis (HR [95% CI]: 1.069 [1.013-1.128], P = 0.016) and remained a significant predictor of the occurrence of AKI after adjustment for comorbidities and the application of a mechanical ventilator. Diabetes, AKI, and the application of a continuous renal replacement therapy (CRRT) were risk factors for mortality in the univariate analysis (HR [95% CI]: diabetes; 10.133 [1.692-60.697], AKI; 12.744 [1.418-114.565], CRRT; 10.254 [1.626-64.666], respectively). Here, we report renal complications and their prognosis in 30 Korean patients with MERS-CoV.",2015 Dec 30,"['Cha, Ran-hui', 'Joh, Joon-Sung', 'Jeong, Ina', 'Lee, Ji Yeon', 'Shin, Hyoung-Shik', 'Kim, Gayeon', 'Kim, Yeonjae', None]",J Korean Med Sci,,,True
e3b596fd33a870737d10b8f5c7fbcf9d3d0aa514,PMC,Penile rehabilitation and cancer spread,http://dx.doi.org/10.12965/jer.150267,PMC4697775,26730377,CC BY-NC,,2015 Dec 31,"Kim, Khae Hawn",J Exerc Rehabil,,,True
a60e292d31e4bb27e20f3ace17fc295ad60990c8,PMC,"Pre-Travel Medical Preparation of Business and Occupational Travelers: An Analysis of the Global TravEpiNet Consortium, 2009 to 2012",http://dx.doi.org/10.1097/JOM.0000000000000602,PMC4697958,26479857,CC BY-NC-ND,"The aim of the study was to understand more about pre-travel preparations and itineraries of business and occupational travelers. METHODS: De-identified data from 18 Global TravEpiNet clinics from January 2009 to December 2012 were analyzed. RESULTS: Of 23,534 travelers, 61% were non-occupational and 39% occupational. Business travelers were more likely to be men, had short times to departure and shorter trip durations, and commonly refused influenza, meningococcal, and hepatitis B vaccines. Most business travelers indicated that employers suggested the pre-travel health consultation, whereas non-occupational travelers sought consultations because of travel health concerns. CONCLUSIONS: Sub-groups of occupational travelers have characteristic profiles, with business travelers being particularly distinct. Employers play a role in encouraging business travelers to seek pre-travel consultations. Such consultations, even if scheduled immediately before travel, can identify vaccination gaps and increase coverage.",2016 Jan 30,"['Khan, Nomana M.', 'Jentes, Emily S.', 'Brown, Clive', 'Han, Pauline', 'Rao, Sowmya R.', 'Kozarsky, Phyllis', 'Hagmann, Stefan H.F.', 'LaRocque, Regina C.', 'Ryan, Edward T.', None]",J Occup Environ Med,,,True
7e0195ed4cec2a365ca4668e68a6b8ebc29e7d83,PMC,Widening participation would be key in enhancing bioinformatics and genomics research in Africa,http://dx.doi.org/10.1016/j.atg.2015.09.001,PMC4699381,26767163,CC BY-NC-ND,"Bioinformatics and genome science (BGS) are gradually gaining roots in Africa, contributing to studies that are leading to improved understanding of health, disease, agriculture and food security. While a few African countries have established foundations for research and training in these areas, BGS appear to be limited to only a few institutions in specific African countries. However, improving the disciplines in Africa will require pragmatic efforts to expand training and research partnerships to scientists in yet-unreached institutions. Here, we discuss the need to expand BGS programmes in Africa, and propose mechanisms to do so.",2015 Sep 16,"['Karikari, Thomas K.', 'Quansah, Emmanuel', 'Mohamed, Wael M.Y.']",Appl Transl Genom,,,False
711ffbd9492fb8100b4c89fea6842c38682e4410,PMC,Elevated level of renal xanthine oxidase mRNA transcription after nephropathogenic infectious bronchitis virus infection in growing layers,http://dx.doi.org/10.4142/jvs.2015.16.4.423,PMC4701734,26119168,CC BY-NC,"To assess relationships between xanthine oxidase (XOD) and nephropathogenic infectious bronchitis virus (NIBV) infection, 240 growing layers (35 days old) were randomly divided into two groups (infected and control) of 120 chickens each. Each chicken in the control and infected group was intranasally inoculated with 0.2 mL sterile physiological saline and virus, respectively, after which serum antioxidant parameters and renal XOD mRNA expression in growing layers were evaluated at 8, 15 and 22 days post-inoculation (dpi). The results showed that serum glutathione peroxidase and superoxide dismutase activities in the infected group were significantly lower than in the control group at 8 and 15 dpi (p < 0.01), while serum malondialdehyde concentrations were significantly higher (p < 0.01). The serum uric acid was significantly higher than that of the control group at 15 dpi (p < 0.01). In addition, the kidney mRNA transcript level and serum activity of XOD in the infected group was significantly higher than that of the control group at 8, 15 and 22 dpi (p < 0.05). The results indicated that NIBV infection could cause the increases of renal XOD gene transcription and serum XOD activity, leading to hyperuricemia and reduction of antioxidants in the body.",2015 Dec 17,"['Lin, Huayuan', 'Huang, Qiqi', 'Guo, Xiaoquan', 'Liu, Ping', 'Liu, Weilian', 'Zou, Yuelong', 'Zhu, Shuliang', 'Deng, Guangfu', 'Kuang, Jun', 'Zhang, Caiying', 'Cao, Huabin', 'Hu, Guoliang']",J Vet Sci,,,True
1a2900a53677a6c68ff37167c31ca33ad219acdb,PMC,Magnetic nanoparticle based purification and enzyme-linked immunosorbent assay using monoclonal antibody against enrofloxacin,http://dx.doi.org/10.4142/jvs.2015.16.4.431,PMC4701735,26040610,CC BY-NC,"Monoclonal anti-enrofloxacin antibody was prepared for a direct competitive enzyme-linked immunosorbent assay (ELISA) and purification system using monoclonal antibody (mAb) coupled magnetic nanoparticles (MNPs). The IC(50) values of the developed mAb for enrofloxacin (ENR), ciprofloxacin, difloxacin, sarafloxacin, pefloxacin, and norfloxacin were 5.0, 8.3, 9.7, 21.7, 36.0, and 63.7 ng/mL, respectively. The lowest detectable level of ENR was 0.7 ng/mL in the prepared ELISA system. To validate the developed ELISA in the food matrix, known amounts of ENR were spiked in meat and egg samples at 10, 20 and 30 ng/mL. Recoveries for ENR ranged from 72.9 to 113.16% with a coefficient of variation (CV) of 2.42 to 10.11%. The applicability of the mAb-MNP system was verified by testing the recoveries for ENR residue in three different matrices. Recoveries for ENR ranged from 75.16 to 86.36%, while the CV ranged from 5.08 to 11.53%. Overall, ENR-specific monoclonal antibody was prepared and developed for use in competitive to ELISAs for the detection of ENR in animal meat samples. Furthermore, we suggest that a purification system for ENR using mAb-coupled MNPs could be useful for determination of ENR residue in food.",2015 Dec 17,"['Kim, Nam-Gun', 'Kim, Myeong-Ae', 'Park, Young-Il', 'Jung, Tae-Sung', 'Son, Seong-Wan', 'So, ByungJae', 'Kang, Hwan-Goo']",J Vet Sci,,,True
0e7c4297d1710cac2a64886cb9a748777b0cd03d,PMC,Suppression of Drug Resistance in Dengue Virus,http://dx.doi.org/10.1128/mBio.01960-15,PMC4701834,26670386,CC BY-NC-SA,"Dengue virus is a major human pathogen responsible for 400 million infections yearly. As with other RNA viruses, daunting challenges to antiviral design exist due to the high error rates of RNA-dependent RNA synthesis. Indeed, treatment of dengue virus infection with a nucleoside analog resulted in the expected genetic selection of resistant viruses in tissue culture and in mice. However, when the function of the oligomeric core protein was inhibited, no detectable selection of drug resistance in tissue culture or in mice was detected, despite the presence of drug-resistant variants in the population. Suppressed selection of drug-resistant virus correlated with cooligomerization of the targeted drug-susceptible and drug-resistant core proteins. The concept of “dominant drug targets,” in which inhibition of oligomeric viral assemblages leads to the formation of drug-susceptible chimeras, can therefore be used to prevent the outgrowth of drug resistance during dengue virus infection.",2015 Dec 15,"['Mateo, Roberto', 'Nagamine, Claude M.', 'Kirkegaard, Karla']",mBio,,,True
3f7e7ab258a23bbd9b9b47a3b863c24daeb0f82c,PMC,Genome-Wide Gene Expression Analysis Identifies the Proto-oncogene Tyrosine-Protein Kinase Src as a Crucial Virulence Determinant of Infectious Laryngotracheitis Virus in Chicken Cells,http://dx.doi.org/10.1128/JVI.01817-15,PMC4702564,26446601,CC BY-NC-SA,"Given the side effects of vaccination against infectious laryngotracheitis (ILT), novel strategies for ILT control and therapy are urgently needed. The modulation of host-virus interactions is a promising strategy to combat the virus; however, the interactions between the host and avian ILT herpesvirus (ILTV) are unclear. Using genome-wide transcriptome studies in combination with a bioinformatic analysis, we identified proto-oncogene tyrosine-protein kinase Src (Src) to be an important modulator of ILTV infection. Src controls the virulence of ILTV and is phosphorylated upon ILTV infection. Functional studies revealed that Src prolongs the survival of host cells by increasing the threshold of virus-induced cell death. Therefore, Src is essential for viral replication in vitro and in ovo but is not required for ILTV-induced cell death. Furthermore, our results identify a positive-feedback loop between Src and the tyrosine kinase focal adhesion kinase (FAK), which is necessary for the phosphorylation of either Src or FAK and is required for Src to modulate ILTV infection. To the best of our knowledge, we are the first to identify a key host regulator controlling host-ILTV interactions. We believe that our findings have revealed a new potential therapeutic target for ILT control and therapy. IMPORTANCE Despite the extensive administration of live attenuated vaccines starting from the mid-20th century and the administration of recombinant vaccines in recent years, infectious laryngotracheitis (ILT) outbreaks due to avian ILT herpesvirus (ILTV) occur worldwide annually. Presently, there are no drugs or control strategies that effectively treat ILT. Targeting of host-virus interactions is considered to be a promising strategy for controlling ILTV infections. However, little is known about the mechanisms governing host-ILTV interactions. The results from our study advance our understanding of host-ILTV interactions on a molecular level and provide experimental evidence that it is possible to control ILT via the manipulation of host-virus interactions.",2015 Dec 17,"['Li, Hai', 'Wang, Fengjie', 'Han, Zongxi', 'Gao, Qi', 'Li, Huixin', 'Shao, Yuhao', 'Sun, Nana', 'Liu, Shengwang']",J Virol,,,False
6c3132687a4cd25b59f39f851b6b924c99afe345,PMC,Genome-Wide Gene Expression Analysis Identifies the Proto-oncogene Tyrosine-Protein Kinase Src as a Crucial Virulence Determinant of Infectious Laryngotracheitis Virus in Chicken Cells,http://dx.doi.org/10.1128/JVI.01817-15,PMC4702564,26446601,CC BY-NC-SA,"Given the side effects of vaccination against infectious laryngotracheitis (ILT), novel strategies for ILT control and therapy are urgently needed. The modulation of host-virus interactions is a promising strategy to combat the virus; however, the interactions between the host and avian ILT herpesvirus (ILTV) are unclear. Using genome-wide transcriptome studies in combination with a bioinformatic analysis, we identified proto-oncogene tyrosine-protein kinase Src (Src) to be an important modulator of ILTV infection. Src controls the virulence of ILTV and is phosphorylated upon ILTV infection. Functional studies revealed that Src prolongs the survival of host cells by increasing the threshold of virus-induced cell death. Therefore, Src is essential for viral replication in vitro and in ovo but is not required for ILTV-induced cell death. Furthermore, our results identify a positive-feedback loop between Src and the tyrosine kinase focal adhesion kinase (FAK), which is necessary for the phosphorylation of either Src or FAK and is required for Src to modulate ILTV infection. To the best of our knowledge, we are the first to identify a key host regulator controlling host-ILTV interactions. We believe that our findings have revealed a new potential therapeutic target for ILT control and therapy. IMPORTANCE Despite the extensive administration of live attenuated vaccines starting from the mid-20th century and the administration of recombinant vaccines in recent years, infectious laryngotracheitis (ILT) outbreaks due to avian ILT herpesvirus (ILTV) occur worldwide annually. Presently, there are no drugs or control strategies that effectively treat ILT. Targeting of host-virus interactions is considered to be a promising strategy for controlling ILTV infections. However, little is known about the mechanisms governing host-ILTV interactions. The results from our study advance our understanding of host-ILTV interactions on a molecular level and provide experimental evidence that it is possible to control ILT via the manipulation of host-virus interactions.",2015 Dec 17,"['Li, Hai', 'Wang, Fengjie', 'Han, Zongxi', 'Gao, Qi', 'Li, Huixin', 'Shao, Yuhao', 'Sun, Nana', 'Liu, Shengwang']",J Virol,,,True
bcc562cf2076fa55f32a63255fa5f71d0bed4f14,PMC,Modulation of nasopharyngeal innate defenses by viral coinfection predisposes individuals to experimental pneumococcal carriage,http://dx.doi.org/10.1038/mi.2015.35,PMC4703943,25921341,CC BY-NC-ND,"Increased nasopharyngeal colonization density has been associated with pneumonia. We used experimental human pneumococcal carriage to investigate whether upper respiratory tract viral infection predisposes individuals to carriage. A total of 101 healthy subjects were screened for respiratory virus before pneumococcal intranasal challenge. Virus was associated with increased odds of colonization (75% virus positive became colonized vs. 46% virus-negative subjects; P=0.02). Nasal Factor H (FH) levels were increased in virus-positive subjects and were associated with increased colonization density. Using an in vitro epithelial model we explored the impact of increased mucosal FH in the context of coinfection. Epithelial inflammation and FH binding resulted in increased pneumococcal adherence to the epithelium. Binding was partially blocked by antibodies targeting the FH-binding protein Pneumococcal surface protein C (PspC). PspC epitope mapping revealed individuals lacked antibodies against the FH binding region. We propose that FH binding to PspC in vivo masks this binding site, enabling FH to facilitate pneumococcal/epithelial attachment during viral infection despite the presence of anti-PspC antibodies. We propose that a PspC-based vaccine lacking binding to FH could reduce pneumococcal colonization, and may have enhanced protection in those with underlying viral infection.",2016 Jan 29,"['Glennie, S', 'Gritzfeld, J F', 'Pennington, S H', 'Garner-Jones, M', 'Coombes, N', 'Hopkins, M J', 'Vadesilho, C F', 'Miyaji, E N', 'Wang, D', 'Wright, A D', 'Collins, A M', 'Gordon, S B', 'Ferreira, D M']",Mucosal Immunol,,,True
e46ad16565574b59346fd489e0a3b2ad97df5dab,PMC,Modulation of nasopharyngeal innate defenses by viral coinfection predisposes individuals to experimental pneumococcal carriage,http://dx.doi.org/10.1038/mi.2015.35,PMC4703943,25921341,CC BY-NC-ND,"Increased nasopharyngeal colonization density has been associated with pneumonia. We used experimental human pneumococcal carriage to investigate whether upper respiratory tract viral infection predisposes individuals to carriage. A total of 101 healthy subjects were screened for respiratory virus before pneumococcal intranasal challenge. Virus was associated with increased odds of colonization (75% virus positive became colonized vs. 46% virus-negative subjects; P=0.02). Nasal Factor H (FH) levels were increased in virus-positive subjects and were associated with increased colonization density. Using an in vitro epithelial model we explored the impact of increased mucosal FH in the context of coinfection. Epithelial inflammation and FH binding resulted in increased pneumococcal adherence to the epithelium. Binding was partially blocked by antibodies targeting the FH-binding protein Pneumococcal surface protein C (PspC). PspC epitope mapping revealed individuals lacked antibodies against the FH binding region. We propose that FH binding to PspC in vivo masks this binding site, enabling FH to facilitate pneumococcal/epithelial attachment during viral infection despite the presence of anti-PspC antibodies. We propose that a PspC-based vaccine lacking binding to FH could reduce pneumococcal colonization, and may have enhanced protection in those with underlying viral infection.",2016 Jan 29,"['Glennie, S', 'Gritzfeld, J F', 'Pennington, S H', 'Garner-Jones, M', 'Coombes, N', 'Hopkins, M J', 'Vadesilho, C F', 'Miyaji, E N', 'Wang, D', 'Wright, A D', 'Collins, A M', 'Gordon, S B', 'Ferreira, D M']",Mucosal Immunol,,,False
4564dfbcb341f91caefc5a880a127a629416c1c6,PMC,Anti-foot-and-mouth disease virus effects of Chinese herbal kombucha in vivo,http://dx.doi.org/10.1590/S1517-838246420140701,PMC4704643,26691487,CC BY-NC,"The foot and mouth disease virus (FMDV) is sensitive to acids and can be inactivated by exposure to low pH conditions. Spraying animals at risk of infection with suspensions of acid-forming microorganisms has been identified as a potential strategy for preventing FMD. Kombucha is one of the most strongly acid-forming symbiotic probiotics and could thus be an effective agent with which to implement this strategy. Moreover, certain Chinese herbal extracts are known to have broad-spectrum antiviral effects. Chinese herbal kombucha can be prepared by fermenting Chinese herbal extracts with a kombucha culture. Previous studies demonstrated that Chinese herbal kombucha prepared in this way efficiently inhibits FMDV replication in vitro. To assess the inhibitory effects of Chinese herbal kombucha against FMDV in vitro, swine challenged by intramuscular injection with 1000 SID(50) of swine FMDV serotype O strain O/China/99 after treatment with Chinese herbal kombucha were partially protected against infection, as demonstrated by a lack of clinical symptoms and qRT-PCR analysis. In a large scale field trial, spraying cattle in an FMD outbreak zone with kombucha protected against infection. Chinese herbal kombucha may be a useful probiotic agent for managing FMD outbreaks.",2015 Dec 1,"['Fu, Naifang', 'Wu, Juncai', 'Lv, Lv', 'He, Jijun', 'Jiang, Shengjun']",Braz J Microbiol,,,True
cc18c54521951016de6597611b735b2f553825bb,PMC,Gastrointestinal granuloma due to Candida albicans in an immunocompetent cat,http://dx.doi.org/10.1016/j.mmcr.2015.12.002,PMC4706628,26862475,CC BY-NC-ND,"A 3.5 year-old cat was admitted to the University of Melbourne Veterinary Teaching Hospital for chronic vomiting. Abdominal ultrasonography revealed a focal, circumferential thickening of the wall of the duodenum extending from the pylorus aborally for 3 cm, and an enlarged gastric lymph node. Cytology of fine-needle aspirates of the intestinal mass and lymph node revealed an eosinophilic inflammatory infiltrate and numerous extracellular septate acute angle branching fungal-type hyphae. Occasional hyphae had globose terminal ends, as well as round to oval blastospores and germ tubes. Candida albicans was cultured from a surgical biopsy of the duodenal mass. No underlying host immunodeficiencies were identified. Passage of an abrasive intestinal foreign body was suspected to have caused intestinal mucosal damage resulting in focal intestinal candidiasis. The cat was treated with a short course of oral itraconazole and all clinical signs resolved.",2015 Dec 12,"['Duchaussoy, Anne-Claire', 'Rose, Annie', 'Talbot, Jessica J.', 'Barrs, Vanessa R.']",Med Mycol Case Rep,,,False
c9bf6547ad546ca4338e790c4fbe75af4c5b6ee8,PMC,"Pilot study of participant-collected nasal swabs for acute respiratory infections in a low-income, urban population",http://dx.doi.org/10.2147/CLEP.S95847,PMC4708198,26793005,CC BY-NC,"OBJECTIVE: To assess the feasibility and validity of unsupervised participant-collected nasal swabs to detect respiratory pathogens in a low-income, urban minority population. METHODS: This project was conducted as part of an ongoing community-based surveillance study in New York City to identify viral etiologies of acute respiratory infection. In January 2014, following sample collection by trained research assistants, participants with acute respiratory infection from 30 households subsequently collected and returned a self-collected/parent-collected nasal swab via mail. Self/parental swabs corresponding with positive reverse transcription polymerase chain reaction primary research samples were analyzed. RESULTS: Nearly all (96.8%, n=30/31) households agreed to participate; 100% reported returning the sample and 29 were received (median time: 8 days). Most (18; 62.1%) of the primary research samples were positive. For eight influenza-positive research samples, seven (87.5%) self-swabs were also positive. For ten other respiratory pathogen-positive research samples, eight (80.0%) self-swabs were positive. Sensitivity of self-swabs for any respiratory pathogen was 83.3% and 87.5% for influenza, and specificity for both was 100%. There was no relationship between level of education and concordance of results between positive research samples and their matching participant swab. CONCLUSION: In this pilot study, self-swabbing was feasible and valid in a low-income, urban minority population.",2016 Jan 6,"['Vargas, Celibell Y', 'Wang, Liqun', 'Castellanos de Belliard, Yaritza', 'Morban, Maria', 'Diaz, Hilbania', 'Larson, Elaine L', 'LaRussa, Philip', 'Saiman, Lisa', 'Stockwell, Melissa S']",Clin Epidemiol,,,True
2bfb845e6afaaa4d43ebd7a79dc3e092e0168d29,PMC,Recent insights into the biological activities and drug delivery systems of tanshinones,http://dx.doi.org/10.2147/IJN.S84035,PMC4708214,26792989,CC BY-NC,"Tanshinones, the major lipid-soluble pharmacological constituents of the Chinese medicinal herb Tanshen (Salvia miltiorrhiza), have attracted growing scientific attention because of the prospective biomedical applications of these compounds. Numerous pharmacological activities, including anti-inflammatory, anticancer, and cardio-cerebrovascular protection activities, are exhibited by the three primary bioactive constituents among the tanshinones, ie, tanshinone I (TNI), tanshinone IIA (TNIIA), and cryptotanshinone (CPT). However, due to their poor solubility and low dissolution rate, the clinical applications of TNI, TNIIA, and CPT are limited. To solve these problems, many studies have focused on loading tanshinones into liposomes, nanoparticles, microemulsions, cyclodextrin inclusions, solid dispersions, and so on. In this review, we aim to offer an updated summary of the biological activities and drug delivery systems of tanshinones to provide a reference for these constituents in clinical applications.",2016 Jan 5,"['Cai, Yuee', 'Zhang, Wenji', 'Chen, Zirong', 'Shi, Zhi', 'He, Chengwei', 'Chen, Meiwan']",Int J Nanomedicine,,,True
dd4ce30ff12f64b4cc7327406db2d77e5a9a66b9,PMC,Ubiquitin in the activation and attenuation of innate antiviral immunity,http://dx.doi.org/10.1084/jem.20151531,PMC4710203,26712804,CC BY-NC-SA,"Viral infection activates danger signals that are transmitted via the retinoic acid–inducible gene 1–like receptor (RLR), nucleotide-binding oligomerization domain-like receptor (NLR), and Toll-like receptor (TLR) protein signaling cascades. This places host cells in an antiviral posture by up-regulating antiviral cytokines including type-I interferon (IFN-I). Ubiquitin modifications and cross-talk between proteins within these signaling cascades potentiate IFN-I expression, and inversely, a growing number of viruses are found to weaponize the ubiquitin modification system to suppress IFN-I. Here we review how host- and virus-directed ubiquitin modification of proteins in the RLR, NLR, and TLR antiviral signaling cascades modulate IFN-I expression.",2016 Jan 11,"['Heaton, Steven M.', 'Borg, Natalie A.', 'Dixit, Vishva M.']",J Exp Med,,,True
dfa3dbdc7b28b9075361efcb919d3a1b19636edd,PMC,Emerging roles of interferon-stimulated genes in the innate immune response to hepatitis C virus infection,http://dx.doi.org/10.1038/cmi.2014.127,PMC4712384,25544499,CC BY-NC-ND,"Infection with hepatitis C virus (HCV), a major viral cause of chronic liver disease, frequently progresses to steatosis and cirrhosis, which can lead to hepatocellular carcinoma. HCV infection strongly induces host responses, such as the activation of the unfolded protein response, autophagy and the innate immune response. Upon HCV infection, the host induces the interferon (IFN)-mediated frontline defense to limit virus replication. Conversely, HCV employs diverse strategies to escape host innate immune surveillance. Type I IFN elicits its antiviral actions by inducing a wide array of IFN-stimulated genes (ISGs). Nevertheless, the mechanisms by which these ISGs participate in IFN-mediated anti-HCV actions remain largely unknown. In this review, we first outline the signaling pathways known to be involved in the production of type I IFN and ISGs and the tactics that HCV uses to subvert innate immunity. Then, we summarize the effector mechanisms of scaffold ISGs known to modulate IFN function in HCV replication. We also highlight the potential functions of emerging ISGs, which were identified from genome-wide siRNA screens, in HCV replication. Finally, we discuss the functions of several cellular determinants critical for regulating host immunity in HCV replication. This review will provide a basis for understanding the complexity and functionality of the pleiotropic IFN system in HCV infection. Elucidation of the specificity and the mode of action of these emerging ISGs will also help to identify novel cellular targets against which effective HCV therapeutics can be developed.",2016 Jan 29,"['Wong, Mun-Teng', 'Chen, Steve S-L']",Cell Mol Immunol,,,True
6db877f61327ae24341591d620abda3793639462,PMC,Survey of Clinical Laboratory Practices for 2015 Middle East Respiratory Syndrome Coronavirus Outbreak in the Republic of Korea,http://dx.doi.org/10.3343/alm.2016.36.2.154,PMC4713849,26709263,CC BY-NC,"BACKGROUND: It is crucial to understand the current status of clinical laboratory practices for the largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infections in the Republic of Korea to be well prepared for future emerging infectious diseases. METHODS: We conducted a survey of 49 clinical laboratories in medical institutions and referral medical laboratories. A short questionnaire to survey clinical laboratory practices relating to MERS-CoV diagnostic testing was sent by email to the directors and clinical pathologists in charge of the clinical laboratories performing MERS-CoV testing. The survey focused on testing volume, reporting of results, resources, and laboratory safety. RESULTS: A total of 40 clinical laboratories responded to the survey. A total of 27,009 MERS-CoV real-time reverse transcription PCR (rRT-PCR) tests were performed. Most of the specimens were sputum (73.5%). The median turnaround time (TAT) was 5.29 hr (first and third quartile, 4.11 and 7.48 hr) in 26 medical institutions. The median TAT of more than a half of the laboratories (57.7%) was less than 6 hr. Many laboratories were able to perform tests throughout the whole week. Laboratory biosafety preparedness included class II biosafety cabinets (100%); separated pre-PCR, PCR, and post-PCR rooms (88.6%); negative pressure pretreatment rooms (48.6%); and negative pressure sputum collection rooms (20.0%). CONCLUSIONS: Clinical laboratories were able to quickly expand their diagnostic capacity in response to the 2015 MERS-CoV outbreak. Our results show that clinical laboratories play an important role in the maintenance and enhancement of laboratory response in preparation for future emerging infections.",2016 Mar 18,"['Lee, Mi-Kyung', 'Kim, Sinyoung', 'Kim, Mi-Na', 'Kweon, Oh Joo', 'Lim, Yong Kwan', 'Ki, Chang-Seok', 'Kim, Jae-Seok', 'Seong, Moon-Woo', 'Sung, Heungsup', 'Yong, Dongeun', 'Lee, Hyukmin', 'Choi, Jong-Rak', 'Kim, Jeong-Ho', None]",Ann Lab Med,,,True
05e5a2bca07922fe0bd52185f4ccaae1b8b154f6,PMC,A phylogenetically distinct Middle East respiratory syndrome coronavirus detected in a dromedary calf from a closed dairy herd in Dubai with rising seroprevalence with age,http://dx.doi.org/10.1038/emi.2015.74,PMC4715164,26632876,CC BY-NC-ND,"Middle East respiratory syndrome coronavirus (MERS-CoV) was detected by monoclonal antibody-based nucleocapsid protein-capture enzyme-linked immunosorbent assay (ELISA), RNA detection, and viral culture from the nasal sample of a 1-month-old dromedary calf in Dubai with sudden death. Whole genome phylogeny showed that this MERS-CoV strain did not cluster with the other MERS-CoV strains from Dubai that we reported recently. Instead, it formed a unique branch more closely related to other MERS-CoV strains from patients in Qatar and Hafr-Al-Batin in Saudi Arabia, as well as the MERS-CoV strains from patients in the recent Korean outbreak, in which the index patient acquired the infection during travel in the eastern part of the Arabian Peninsula. Non-synonymous mutations, resulting in 11 unique amino acid differences, were observed between the MERS-CoV genome from the present study and all the other available MERS-CoV genomes. Among these 11 unique amino acid differences, four were found in ORF1ab, three were found in the S1 domain of the spike protein, and one each was found in the proteins encoded by ORF4b, ORF5, envelope gene, and ORF8. MERS-CoV detection for all other 254 dromedaries in this closed dairy herd was negative by nucleocapsid protein-capture ELISA and RNA detection. MERS-CoV IgG sero-positivity gradually increased in dromedary calves with increasing age, with positivity rates of 75% at zero to three months, 79% at four months, 89% at five to six months, and 90% at seven to twelve months. The development of a rapid antigen detection kit for instantaneous diagnosis is warranted.",2015 Dec 2,"['Wernery, Ulrich', 'Rasoul, IHassab El', 'Wong, Emily YM', 'Joseph, Marina', 'Chen, Yixin', 'Jose, Shanty', 'Tsang, Alan KL', 'Patteril, Nissy Annie Georgy', 'Chen, Honglin', 'Elizabeth, Shyna K', 'Yuen, Kwok-Yung', 'Joseph, Sunitha', 'Xia, Ningshao', 'Wernery, Renate', 'Lau, Susanna KP', 'Woo, Patrick CY']",Emerg Microbes Infect,,,True
200eee0824f97c373a016370a5292af80121f351,PMC,Silent osteonecrosis of the femoral head following high-dose corticosteroids in patients with systemic rheumatic diseases,,PMC4715417,26793650,CC BY-NC,"Background: Osteonecrosis (ON) is known to be one of the most disabling complications following corticosteroid (CS) medications. However, evidence regarding risk of asymptomatic prevalence of ON among different diseases and the impact of variable steroid regimens are conflicting. We aimed to determine the prevalence of ON of femoral head in asymptomatic patients with systemic rheumatic diseases who received high-dose CS and also clarify its relationship with different dosages and regimens. Methods: In this cross-sectional study, 50 consecutive patients receiving high-dose CS for rheumatic diseases who have no pelvic pain were recruited. MRI of both hips was performed on all patients using a 1.5 Tesla to diagnose ON. Results: Of 50 subjects, 18 (36%) developed ON of the femoral head. Groups with and without ON were comparable in terms of sex, age and mean starting CS dose. There was no statistical difference in the type of CS regimen including daily dose, peak dose and cumulative dose between the two groups. However, silent ON was associated with both the cumulative CS dose and the duration of CS therapy. Conclusion: According to high prevalence of ON in our selected patients with no other identifiable risk factor for ON, monitoring of high risk patients with periodic hip MRI would help diagnose necrosis in early stage.",2015 Sep 8,"['Kianmehr, Nahid', 'Bidari, Ali', 'Mofidi, Mani', 'Bahar, Nasim']",Med J Islam Repub Iran,,,True
4a9469fd152806179cbbf936e6ec7df22930efce,PMC,The Same Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) yet Different Outbreak Patterns and Public Health Impacts on the Far East Expert Opinion from the Rapid Response Team of the Republic of Korea,http://dx.doi.org/10.3947/ic.2015.47.4.247,PMC4716276,26788408,CC BY-NC,"A Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) outbreak, the largest outbreak outside the Middle East in 2012, occurred in the Republic of Korea and resulted in a large number of cases, with 186 infected people, including 38 deaths. A Rapid Response Team (RRT) was appointed after a request from the Korean government on June 8, 2015 calling for specialists to manage and control the MERS-CoV outbreak. This report presents the opinion of the RRT who worked to manage this healthcare-associated MERS-CoV outbreak in Korea.",2015 Dec 30,,Infect Chemother,,,True
b1ef060481c45d71c380d4ac3ec6d8a4f0f26945,PMC,Viral Shedding and Environmental Cleaning in Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.3947/ic.2015.47.4.252,PMC4716277,26788409,CC BY-NC,"Viral shedding lasted 31 and 19 days from symptom onset in two patients with east respiratory syndrome coronavirus (MERS-CoV) pneumonia, respectively. Environmental real-time RT-PCR was weakly positive for bed guardrail and monitors. Even after cleaning the monitors with 70% alcohol-based disinfectant, RT-PCR was still weakly positive, and converted to negative only after wiping with diluted sodium chlorite. Further studies are required to clarify the appropriate methods to clean environments during and after treatment of patients with MERS-CoV infection.",2015 Dec 30,"['Song, Joon Young', 'Cheong, Hee Jin', 'Choi, Min Joo', 'Jeon, Ji Ho', 'Kang, Seong Hee', 'Jeong, Eun Ju', 'Yoon, Jin Gu', 'Lee, Saem Na', 'Kim, Sung Ran', 'Noh, Ji Yun', 'Kim, Woo Joo']",Infect Chemother,,,True
7e2390fbb36e75e858fe46a1c81266144ab176de,PMC,Middle East Respiratory Syndrome Infection Control and Prevention Guideline for Healthcare Facilities,http://dx.doi.org/10.3947/ic.2015.47.4.278,PMC4716282,26788414,CC BY-NC,"Middle East Respiratory Syndrome (MERS) is an acute viral respiratory illness with high mortality caused by a new strain of betacoronavirus (MERS-CoV). Since the report of the first patient in Saudi Arabia in 2012, large-scale outbreaks through hospital-acquired infection and inter-hospital transmission have been reported. Most of the patients reported in South Korea were also infected in hospital settings. Therefore, to eliminate the spread of MERS-CoV, infection prevention and control measures should be implemented with rigor. The present guideline has been drafted on the basis of the experiences of infection control in the South Korean hospitals involved in the recent MERS outbreak and on domestic and international infection prevention and control guidelines. To ensure efficient MERS-CoV infection prevention and control, care should be taken to provide comprehensive infection control measures including contact control, hand hygiene, personal protective equipment, disinfection, and environmental cleaning.",2015 Dec 30,"['Kim, Jin Yong', 'Song, Joon Young', 'Yoon, Young Kyung', 'Choi, Seong-Ho', 'Song, Young Goo', 'Kim, Sung-Ran', 'Son, Hee-Jung', 'Jeong, Sun-Young', 'Choi, Jung-Hwa', 'Kim, Kyung Mi', 'Yoon, Hee Jung', 'Choi, Jun Yong', 'Kim, Tae Hyong', 'Choi, Young Hwa', 'Kim, Hong Bin', 'Yoon, Ji Hyun', 'Lee, Jacob', 'Eom, Joong Sik', 'Lee, Sang-Oh', 'Oh, Won Sup', 'Choi, Jung-Hyun', 'Yoo, Jin-Hong', 'Kim, Woo Joo', 'Cheong, Hee Jin']",Infect Chemother,,,True
6708dd7c675e9a967e9f5487cd3f3b6bc225775a,PMC,Middle East Respiratory Syndrome Infection Control and Prevention Guideline for Healthcare Facilities,http://dx.doi.org/10.3947/ic.2015.47.4.278,PMC4716282,26788414,CC BY-NC,"Middle East Respiratory Syndrome (MERS) is an acute viral respiratory illness with high mortality caused by a new strain of betacoronavirus (MERS-CoV). Since the report of the first patient in Saudi Arabia in 2012, large-scale outbreaks through hospital-acquired infection and inter-hospital transmission have been reported. Most of the patients reported in South Korea were also infected in hospital settings. Therefore, to eliminate the spread of MERS-CoV, infection prevention and control measures should be implemented with rigor. The present guideline has been drafted on the basis of the experiences of infection control in the South Korean hospitals involved in the recent MERS outbreak and on domestic and international infection prevention and control guidelines. To ensure efficient MERS-CoV infection prevention and control, care should be taken to provide comprehensive infection control measures including contact control, hand hygiene, personal protective equipment, disinfection, and environmental cleaning.",2015 Dec 30,"['Kim, Jin Yong', 'Song, Joon Young', 'Yoon, Young Kyung', 'Choi, Seong-Ho', 'Song, Young Goo', 'Kim, Sung-Ran', 'Son, Hee-Jung', 'Jeong, Sun-Young', 'Choi, Jung-Hwa', 'Kim, Kyung Mi', 'Yoon, Hee Jung', 'Choi, Jun Yong', 'Kim, Tae Hyong', 'Choi, Young Hwa', 'Kim, Hong Bin', 'Yoon, Ji Hyun', 'Lee, Jacob', 'Eom, Joong Sik', 'Lee, Sang-Oh', 'Oh, Won Sup', 'Choi, Jung-Hyun', 'Yoo, Jin-Hong', 'Kim, Woo Joo', 'Cheong, Hee Jin']",Infect Chemother,,,True
aaeb1b254b13be853e9401cacbf8d18a6b5b3236,PMC,Silent War to Emerging or Re-emerging Respiratory Infection Diseases Badly Kept in Mind,http://dx.doi.org/10.4103/0366-6999.162492,PMC4717996,26265603,CC BY-NC-SA,,2015 Aug 20,"['Zheng, Ya-Li', 'Gao, Zhan-Cheng']",Chin Med J (Engl),,,True
d843363f9656abc2037bd77bd018dcbbd541d849,PMC,Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza. Part I: influenza life-cycle and currently available drugs,,PMC4718311,25902573,CC BY-NC-ND,"Influenza is a contagious respiratory acute viral disease characterized by a short incubation period, high fever and respiratory and systemic symptoms. The burden of influenza is very heavy. Indeed, the World Health Organization (WHO) estimates that annual epidemics affect 5-15% of the world's population, causing up to 4-5 million severe cases and from 250,000 to 500,000 deaths. In order to design anti-influenza molecules and compounds, it is important to understand the complex replication cycle of the influenza virus. Replication is achieved through various stages. First, the virus must engage the sialic acid receptors present on the free surface of the cells of the respiratory tract. The virus can then enter the cells by different routes (clathrin-mediated endocytosis or CME, caveolae-dependent endocytosis or CDE, clathrin-caveolae-independent endocytosis, or macropinocytosis). CME is the most usual pathway; the virus is internalized into an endosomal compartment, from which it must emerge in order to release its nucleic acid into the cytosol. The ribonucleoprotein must then reach the nucleus in order to begin the process of translation of its genes and to transcribe and replicate its nucleic acid. Subsequently, the RNA segments, surrounded by the nucleoproteins, must migrate to the cell membrane in order to enable viral assembly. Finally, the virus must be freed to invade other cells of the respiratory tract. All this is achieved through a synchronized action of molecules that perform multiple enzymatic and catalytic reactions, currently known only in part, and for which many inhibitory or competitive molecules have been studied. Some of these studies have led to the development of drugs that have been approved, such as Amantadine, Rimantadine, Oseltamivir, Zanamivir, Peramivir, Laninamivir, Ribavirin and Arbidol. This review focuses on the influenza lifecycle and on the currently available drugs, while potential antiviral compounds for the prevention and treatment of influenza are considered in the subsequent review.",2014 Sep,"['GASPARINI, R.', 'AMICIZIA, D.', 'LAI, PL.', 'BRAGAZZI, NL.', 'PANATTO, D.']",J Prev Med Hyg,,,True
544a005c6288491bc6229435fddcdec62d6e24b9,PMC,Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza Part II: Future compounds against influenza virus,,PMC4718316,26137785,CC BY-NC-ND,"In the first part of this overview, we described the life cycle of the influenza virus and the pharmacological action of the currently available drugs. This second part provides an overview of the molecular mechanisms and targets of still-experimental drugs for the treatment and management of influenza. Briefly, we can distinguish between compounds with anti-influenza activity that target influenza virus proteins or genes, and molecules that target host components that are essential for viral replication and propagation. These latter compounds have been developed quite recently. Among the first group, we will focus especially on hemagglutinin, M2 channel and neuraminidase inhibitors. The second group of compounds may pave the way for personalized treatment and influenza management. Combination therapies are also discussed. In recent decades, few antiviral molecules against influenza virus infections have been available; this has conditioned their use during human and animal outbreaks. Indeed, during seasonal and pandemic outbreaks, antiviral drugs have usually been administered in mono-therapy and, sometimes, in an uncontrolled manner to farm animals. This has led to the emergence of viral strains displaying resistance, especially to compounds of the amantadane family. For this reason, it is particularly important to develop new antiviral drugs against influenza viruses. Indeed, although vaccination is the most powerful means of mitigating the effects of influenza epidemics, antiviral drugs can be very useful, particularly in delaying the spread of new pandemic viruses, thereby enabling manufacturers to prepare large quantities of pandemic vaccine. In addition, antiviral drugs are particularly valuable in complicated cases of influenza, especially in hospitalized patients. To write this overview, we mined various databases, including Embase, PubChem, DrugBank and Chemical Abstracts Service, and patent repositories.",2014 Dec,"['GASPARINI, R.', 'AMICIZIA, D.', 'LAI, P.L.', 'BRAGAZZI, N.L.', 'PANATTO, D.']",J Prev Med Hyg,,,True
e5eaa60c56eee1eab42525423bbd85b4e99453db,PMC,Middle East Respiratory Syndrome-Coronavirus Infection: A Case Report of Serial Computed Tomographic Findings in a Young Male Patient,http://dx.doi.org/10.3348/kjr.2016.17.1.166,PMC4720805,26798230,CC BY-NC,"Radiologic findings of Middle East respiratory syndrome (MERS), a novel coronavirus infection, have been rarely reported. We report a 30-year-old male presented with fever, abdominal pain, and diarrhea, who was diagnosed with MERS. A chest computed tomographic scan revealed rapidly developed multifocal nodular consolidations with ground-glass opacity halo and mixed consolidation, mainly in the dependent and peripheral areas. After treatment, follow-up imaging showed that these abnormalities markedly decreased but fibrotic changes developed.",2016 Jan 6 Jan-Feb,"['Choi, Won Jin', 'Lee, Ki-Nam', 'Kang, Eun-Ju', 'Lee, Hyuck']",Korean J Radiol,,,True
176fa00106dc0e7b0ef19c0b606aa80cd14e4057,PMC,Comparative Functional Analysis of 12 Mammalian IFN-λ4 Orthologs,http://dx.doi.org/10.1089/jir.2015.0096,PMC4722605,26308395,CC BY-NC,"IFN-λ4 is a novel type-III interferon with strong clinical significance in humans. Only a subset of individuals—up to 10% of Asians, 50% of Europeans, and 90% of Africans—carry the ΔG allele of a genetic variant rs368234815-TT/ΔG and are genetically able to produce IFN-λ4 protein. Carriers of the ΔG allele have impaired ability to clear infection with hepatitis C virus (HCV). IFN-λ4 is also predicted to exist and be functionally important in several nonhuman mammals. In this study, we present the first comparative analysis of 12 mammalian IFN-λ4 orthologs in a human hepatic cell line, HepG2, which supports signaling of the human IFN-λ4. We show that despite differences in protein sequences, functional properties of the recombinant human and nonhuman IFN-λ4 proteins are comparable—they are all expressed as predominantly cytoplasmic proteins that are biologically active for induction of interferon signaling. We show that several IFN-λ4 orthologs can be detected by Western blotting, flow cytometry, and confocal imaging using a monoclonal antibody developed for the human IFN-λ4. Studies of IFN-λ4 in animals should help improve our understanding of the biology of this novel clinically important interferon in normal and disease conditions.",2016 Jan 1,"['Paquin, Ashley', 'Onabajo, Olusegun O.', 'Tang, Wei', 'Prokunina-Olsson, Ludmila']",J Interferon Cytokine Res,,,True
85c11b54d30f4d766259d279c755f5c66469d03b,PMC,Comparative Functional Analysis of 12 Mammalian IFN-λ4 Orthologs,http://dx.doi.org/10.1089/jir.2015.0096,PMC4722605,26308395,CC BY-NC,"IFN-λ4 is a novel type-III interferon with strong clinical significance in humans. Only a subset of individuals—up to 10% of Asians, 50% of Europeans, and 90% of Africans—carry the ΔG allele of a genetic variant rs368234815-TT/ΔG and are genetically able to produce IFN-λ4 protein. Carriers of the ΔG allele have impaired ability to clear infection with hepatitis C virus (HCV). IFN-λ4 is also predicted to exist and be functionally important in several nonhuman mammals. In this study, we present the first comparative analysis of 12 mammalian IFN-λ4 orthologs in a human hepatic cell line, HepG2, which supports signaling of the human IFN-λ4. We show that despite differences in protein sequences, functional properties of the recombinant human and nonhuman IFN-λ4 proteins are comparable—they are all expressed as predominantly cytoplasmic proteins that are biologically active for induction of interferon signaling. We show that several IFN-λ4 orthologs can be detected by Western blotting, flow cytometry, and confocal imaging using a monoclonal antibody developed for the human IFN-λ4. Studies of IFN-λ4 in animals should help improve our understanding of the biology of this novel clinically important interferon in normal and disease conditions.",2016 Jan 1,"['Paquin, Ashley', 'Onabajo, Olusegun O.', 'Tang, Wei', 'Prokunina-Olsson, Ludmila']",J Interferon Cytokine Res,,,False
866072533eae6663236f6795e0c055492b1ecdae,PMC,Comparative Functional Analysis of 12 Mammalian IFN-λ4 Orthologs,http://dx.doi.org/10.1089/jir.2015.0096,PMC4722605,26308395,CC BY-NC,"IFN-λ4 is a novel type-III interferon with strong clinical significance in humans. Only a subset of individuals—up to 10% of Asians, 50% of Europeans, and 90% of Africans—carry the ΔG allele of a genetic variant rs368234815-TT/ΔG and are genetically able to produce IFN-λ4 protein. Carriers of the ΔG allele have impaired ability to clear infection with hepatitis C virus (HCV). IFN-λ4 is also predicted to exist and be functionally important in several nonhuman mammals. In this study, we present the first comparative analysis of 12 mammalian IFN-λ4 orthologs in a human hepatic cell line, HepG2, which supports signaling of the human IFN-λ4. We show that despite differences in protein sequences, functional properties of the recombinant human and nonhuman IFN-λ4 proteins are comparable—they are all expressed as predominantly cytoplasmic proteins that are biologically active for induction of interferon signaling. We show that several IFN-λ4 orthologs can be detected by Western blotting, flow cytometry, and confocal imaging using a monoclonal antibody developed for the human IFN-λ4. Studies of IFN-λ4 in animals should help improve our understanding of the biology of this novel clinically important interferon in normal and disease conditions.",2016 Jan 1,"['Paquin, Ashley', 'Onabajo, Olusegun O.', 'Tang, Wei', 'Prokunina-Olsson, Ludmila']",J Interferon Cytokine Res,,,False
001ebffb65aab84e37a66f73d5a418c251ce821a,PMC,Comparative Functional Analysis of 12 Mammalian IFN-λ4 Orthologs,http://dx.doi.org/10.1089/jir.2015.0096,PMC4722605,26308395,CC BY-NC,"IFN-λ4 is a novel type-III interferon with strong clinical significance in humans. Only a subset of individuals—up to 10% of Asians, 50% of Europeans, and 90% of Africans—carry the ΔG allele of a genetic variant rs368234815-TT/ΔG and are genetically able to produce IFN-λ4 protein. Carriers of the ΔG allele have impaired ability to clear infection with hepatitis C virus (HCV). IFN-λ4 is also predicted to exist and be functionally important in several nonhuman mammals. In this study, we present the first comparative analysis of 12 mammalian IFN-λ4 orthologs in a human hepatic cell line, HepG2, which supports signaling of the human IFN-λ4. We show that despite differences in protein sequences, functional properties of the recombinant human and nonhuman IFN-λ4 proteins are comparable—they are all expressed as predominantly cytoplasmic proteins that are biologically active for induction of interferon signaling. We show that several IFN-λ4 orthologs can be detected by Western blotting, flow cytometry, and confocal imaging using a monoclonal antibody developed for the human IFN-λ4. Studies of IFN-λ4 in animals should help improve our understanding of the biology of this novel clinically important interferon in normal and disease conditions.",2016 Jan 1,"['Paquin, Ashley', 'Onabajo, Olusegun O.', 'Tang, Wei', 'Prokunina-Olsson, Ludmila']",J Interferon Cytokine Res,,,False
fee36413323e9fcb72a1869c555f2b37adc7d080,PMC,Comparative Functional Analysis of 12 Mammalian IFN-λ4 Orthologs,http://dx.doi.org/10.1089/jir.2015.0096,PMC4722605,26308395,CC BY-NC,"IFN-λ4 is a novel type-III interferon with strong clinical significance in humans. Only a subset of individuals—up to 10% of Asians, 50% of Europeans, and 90% of Africans—carry the ΔG allele of a genetic variant rs368234815-TT/ΔG and are genetically able to produce IFN-λ4 protein. Carriers of the ΔG allele have impaired ability to clear infection with hepatitis C virus (HCV). IFN-λ4 is also predicted to exist and be functionally important in several nonhuman mammals. In this study, we present the first comparative analysis of 12 mammalian IFN-λ4 orthologs in a human hepatic cell line, HepG2, which supports signaling of the human IFN-λ4. We show that despite differences in protein sequences, functional properties of the recombinant human and nonhuman IFN-λ4 proteins are comparable—they are all expressed as predominantly cytoplasmic proteins that are biologically active for induction of interferon signaling. We show that several IFN-λ4 orthologs can be detected by Western blotting, flow cytometry, and confocal imaging using a monoclonal antibody developed for the human IFN-λ4. Studies of IFN-λ4 in animals should help improve our understanding of the biology of this novel clinically important interferon in normal and disease conditions.",2016 Jan 1,"['Paquin, Ashley', 'Onabajo, Olusegun O.', 'Tang, Wei', 'Prokunina-Olsson, Ludmila']",J Interferon Cytokine Res,,,False
fb533a0af2fc3935236739c95784f06faf0d6290,PMC,Comparative Functional Analysis of 12 Mammalian IFN-λ4 Orthologs,http://dx.doi.org/10.1089/jir.2015.0096,PMC4722605,26308395,CC BY-NC,"IFN-λ4 is a novel type-III interferon with strong clinical significance in humans. Only a subset of individuals—up to 10% of Asians, 50% of Europeans, and 90% of Africans—carry the ΔG allele of a genetic variant rs368234815-TT/ΔG and are genetically able to produce IFN-λ4 protein. Carriers of the ΔG allele have impaired ability to clear infection with hepatitis C virus (HCV). IFN-λ4 is also predicted to exist and be functionally important in several nonhuman mammals. In this study, we present the first comparative analysis of 12 mammalian IFN-λ4 orthologs in a human hepatic cell line, HepG2, which supports signaling of the human IFN-λ4. We show that despite differences in protein sequences, functional properties of the recombinant human and nonhuman IFN-λ4 proteins are comparable—they are all expressed as predominantly cytoplasmic proteins that are biologically active for induction of interferon signaling. We show that several IFN-λ4 orthologs can be detected by Western blotting, flow cytometry, and confocal imaging using a monoclonal antibody developed for the human IFN-λ4. Studies of IFN-λ4 in animals should help improve our understanding of the biology of this novel clinically important interferon in normal and disease conditions.",2016 Jan 1,"['Paquin, Ashley', 'Onabajo, Olusegun O.', 'Tang, Wei', 'Prokunina-Olsson, Ludmila']",J Interferon Cytokine Res,,,False
541efff1146fcb123189ad615099b67769ed41c5,PMC,Bat consumption in Thailand,http://dx.doi.org/10.3402/iee.v6.29941,PMC4724787,26806167,CC BY-NC,"BACKGROUND: Human consumption of bats poses an increasing public health threat globally. Communities in which bat guano is mined from caves have extensive exposure to bat excreta, often harvest bats for consumption, and are at risk for bat-borne diseases. METHODS: This rapid ethnographic study was conducted in four provinces of Thailand (Ratchaburi, Sakaeo, Nakorn Sawan, and Phitsanulok), where bat guano was mined and sold during the period April–August 2014. The aim of this study was to understand behaviors and risk perceptions associated with bat conservation, exposure to bats and their excreta, and bat consumption. Sixty-seven respondents playing various roles in bat guano mining, packaging, sale, and use as fertilizer participated in the study. Data were collected through interviews and/or focus group discussions. RESULTS: In spite of a bat conservation program dating back to the 1980s, the benefits of conserving bats and the risks associated with bat consumption were not clear and infrequently articulated by study respondents. DISCUSSION: Since bat consumption continues, albeit covertly, the risk of bat-borne diseases remains high. There is an opportunity to reduce the risk of bat-borne diseases in guano-mining communities by strengthening bat conservation efforts and raising awareness of the health risks of bat consumption. Further research is suggested to test behavior change strategies for reducing bat consumption.",2016 Jan 22,"['Suwannarong, Kanokwan', 'Schuler, Sidney']",Infect Ecol Epidemiol,,,True
131af5ab50551638e3ce9a8c615b9b4364f2f34e,PMC,Characterization of a Pathogenic Full-Length cDNA Clone and Transmission Model for Porcine Epidemic Diarrhea Virus Strain PC22A,http://dx.doi.org/10.1128/mBio.01451-15,PMC4724997,26733065,CC BY-NC-SA,"Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic alphacoronavirus. In the United States, highly virulent PEDV strains cause between 80 and 100% mortality in suckling piglets and are rapidly transmitted between animals and farms. To study the genetic factors that regulate pathogenesis and transmission, we developed a molecular clone of PEDV strain PC22A. The infectious-clone-derived PEDV (icPEDV) replicated as efficiently as the parental virus in cell culture and in pigs, resulting in lethal disease in vivo. Importantly, recombinant PEDV was rapidly transmitted to uninoculated pigs via indirect contact, demonstrating virulence and efficient transmission while replicating phenotypes seen in the wild-type virus. Using reverse genetics, we removed open reading frame 3 (ORF3) and replaced this region with a red fluorescent protein (RFP) gene to generate icPEDV-ΔORF3-RFP. icPEDV-ΔORF3-RFP replicated efficiently in vitro and in vivo, was efficiently transmitted among pigs, and produced lethal disease outcomes. However, the diarrheic scores in icPEDV-ΔORF3-RFP-infected pigs were lower than those in wild-type-virus- or icPEDV-infected pigs, and the virus formed smaller plaques than those of PC22A. Together, these data describe the development of a robust reverse-genetics platform for identifying genetic factors that regulate pathogenic outcomes and transmission efficiency in vivo, providing key infrastructural developments for developing and evaluating the efficacy of live attenuated vaccines and therapeutics in a clinical setting.",2016 Jan 5,"['Beall, Anne', 'Yount, Boyd', 'Lin, Chun-Ming', 'Hou, Yixuan', 'Wang, Qiuhong', 'Saif, Linda', 'Baric, Ralph']",mBio,,,True
374f83b1cca6c5caba34833d2cd25febd1cc72f1,PMC,Current views and advances on Paediatric Virology: An update for paediatric trainees,http://dx.doi.org/10.3892/etm.2015.2890,PMC4726865,26889211,CC BY-NC-ND,"Paediatric Virology is a bold new scientific field, which combines Paediatrics with Virology, Epidemiology, Molecular Medicine, Evidence-based Medicine, Clinical Governance, Quality Improvement, Pharmacology and Immunology. The Workshop on Paediatric Virology, which took place on Saturday October 10, 2015 in Athens, Greece, provided an overview of recent views and advances on viral infections occurring in neonates and children. It was included in the official programme of the 20th World Congress on Advances in Oncology and the 18th International Symposium on Molecular Medicine, which attracted over 500 delegates from the five continents. During the Workshop, the topics covered included the challenges of vaccine implementation against human papillomaviruses in countries under financial crisis, strategies for eradicating poliomyelitis and its 60th vaccine anniversary, as well as the debate on the association between autism and vaccination against measles, mumps and rubella. Among the non-vaccine related topics, emphasis was given to viral infections in prematurely born infants and their long-term outcomes, new paediatric intensive care management options for bronchiolitis related to respiratory syncytial virus, the clinical implications of hepatitis B virus and cytomegalovirus genotyping, the Ebola virus threat and preparedness in Paediatric Emergency Departments, oral, oropharynx, laryngeal, nasal and ocular viral infections and Merkel cell polyomavirus as a novel emerging virus of infancy and childhood. In this review, we provide selected presentations and reports discussed at the Workshop.",2016 Jan 24,"['MAMMAS, IOANNIS N.', 'GREENOUGH, ANNE', 'THEODORIDOU, MARIA', 'KRAMVIS, ANNA', 'CHRISTAKI, ILIANA', 'KOUTSAFTIKI, CHRYSSIE', 'KOUTSAKI, MARIA', 'PORTALIOU, DIMITRA M.', 'KOSTAGIANNI, GEORGIA', 'PANAGOPOULOU, PARASKEVI', 'SOURVINOS, GEORGE', 'SPANDIDOS, DEMETRIOS A.']",Exp Ther Med,,,True
27d6ec2664104ba3347a3991ce63d20ebae32d39,PMC,Isolation of Middle East Respiratory Syndrome Coronavirus from a Patient of the 2015 Korean Outbreak,http://dx.doi.org/10.3346/jkms.2016.31.2.315,PMC4729515,26839489,CC BY-NC,"During the 2015 outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Korea, 186 persons were infected, resulting in 38 fatalities. We isolated MERS-CoV from the oropharyngeal sample obtained from a patient of the outbreak. Cytopathic effects showing detachment and rounding of cells were observed in Vero cell cultures 3 days after inoculation of the sample. Spherical virus particles were observed by transmission electron microscopy. Full-length genome sequence of the virus isolate was obtained and phylogenetic analyses showed that it clustered with clade B of MERS-CoV.",2016 Feb 14,"['Park, Wan Beom', 'Kwon, Nak-Jung', 'Choe, Pyoeng Gyun', 'Choi, Su-Jin', 'Oh, Hong Sang', 'Lee, Sang Min', 'Chong, Hyonyong', 'Kim, Jong-Il', 'Song, Kyoung-Ho', 'Bang, Ji Hwan', 'Kim, Eu Suk', 'Kim, Hong-Bin', 'Park, Sang Won', 'Kim, Nam Joong', 'Oh, Myoung-don']",J Korean Med Sci,,,True
c709f22712bf719ea63619fad05d66ce640a7c38,PMC,Lucky China: Efficient Prevention from Middle East Respiratory Syndrome and its Beyond,http://dx.doi.org/10.4103/0366-6999.167292,PMC4736877,26481732,CC BY-NC-SA,,2015 Oct 20,"['Zheng, Ya-Li', 'Li, Ran', 'Gao, Zhan-Cheng']",Chin Med J (Engl),,,True
a45c1bbbc8f619491ce0c5ddc26fadbe7d69c975,PMC,Randomized controlled trial of the effect of regular paracetamol on influenza infection,http://dx.doi.org/10.1111/resp.12685,PMC4738455,26638130,CC BY-NC,"BACKGROUND AND OBJECTIVE: Anti‐pyretic treatment is recommended in the management of influenza infection. In animal models anti‐pyretic treatment increases mortality from influenza. We investigated the effects of paracetamol on viral and clinical outcomes in adults with influenza infection. METHODS: This is a randomized, double‐blind, placebo‐controlled trial of adults aged 18–65 years with influenza‐like illness and positive influenza rapid antigen test. Treatments were 1 g paracetamol four times a day, or matching placebo, for 5 days. Pernasal swabs were taken for influenza quantitative RT‐PCR at Baseline and Days 1, 2 and 5. Temperature and symptom scores were recorded for 5–14 days or time of resolution respectively. The primary outcome variable was area under the curve (AUC) for quantitative PCR log(10) viral load from Baseline to Day 5. RESULTS: A total of 80 participants were randomized: no one was lost to follow up, and one withdrew after 4 days. There were 22 and 24 participants who were influenza PCR‐positive in placebo and in paracetamol groups respectively. Mean (SD) AUC PCR log(10) viral load was 4.40 (0.91) in placebo and 4.64 (0.88) in paracetamol; difference was −0.24, 95% CI: −0.78 to 0.29, P = 0.36. In all participants there were no differences in symptom scores, temperature, time to resolution of illness and health status, with no interaction between randomized treatment and whether influenza was detected by PCR. CONCLUSION: Regular paracetamol had no effect on viral shedding, temperature or clinical symptoms in patients with PCR‐confirmed influenza. There remains an insufficient evidence base for paracetamol use in influenza infection. Clinical trial registration: ACTRN12611000497909 at the Australian New Zealand Clinical Trials Registry.",2016 Feb 6,"['Jefferies, Sarah', 'Braithwaite, Irene', 'Walker, Steven', 'Weatherall, Mark', 'Jennings, Lance', 'Luck, Michelle', 'Barrett, Kevin', 'Siebers, Robert', 'Blackmore, Timothy', 'Beasley, Richard', 'Perrin, Kyle', None]",Respirology,,,True
b32f99009279a618af74a7990d891b38603c0b71,PMC,"Small Non-coding Transfer RNA-Derived RNA Fragments (tRFs): Their Biogenesis, Function and Implication in Human Diseases",http://dx.doi.org/10.5808/GI.2015.13.4.94,PMC4742329,26865839,CC BY-NC,"tRNA-derived RNA fragments (tRFs) are an emerging class of non-coding RNAs (ncRNAs). A growing number of reports have shown that tRFs are not random degradation products but are functional ncRNAs made of specific tRNA cleavage. They play regulatory roles in several biological contexts such as cancer, innate immunity, stress responses, and neurological disorders. In this review, we summarize the biogenesis and functions of tRFs.",2015 Dec 31,"['Fu, Yu', 'Lee, Inhan', 'Lee, Yong Sun', 'Bao, Xiaoyong']",Genomics Inform,,,True
022abf5f202c04e2bbf88d829db9844746e0fb71,PMC,Recent vaccine technology in industrial animals,http://dx.doi.org/10.7774/cevr.2016.5.1.12,PMC4742593,26866019,CC BY-NC,"Various new technologies have been applied for developing vaccines against various animal diseases. Virus-like particle (VLP) vaccine technology was used for manufacturing the porcine circovirus type 2 and RNA particle vaccines based on an alphavirus vector for porcine epidemic diarrhea (PED). Although VLP is classified as a killed-virus vaccine, because its structure is similar to the original virus, it can induce long-term and cell-mediated immunity. The RNA particle vaccine used a Venezuela equine encephalitis (VEE) virus gene as a vector. The VEE virus partial gene can be substituted with the PED virus spike gene. Recombinant vaccines can be produced by substitution of the target gene in the VEE vector. Both of these new vaccine technologies made it possible to control the infectious disease efficiently in a relatively short time.",2016 Jan 27,"['Kim, Hyunil', 'Lee, Yoo-kyoung', 'Kang, Sang Chul', 'Han, Beom Ku', 'Choi, Ki Myung']",Clin Exp Vaccine Res,,,True
e484923f000ae4706e2213031654865cef348def,PMC,Treatment strategies for Middle East respiratory syndrome coronavirus,,PMC4745090,26866060,CC BY-NC,"Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging infectious disease of growing global importance, has caused severe acute respiratory disease in more than 1600 people, resulting in almost 600 deaths. The high case fatality rate, growing geographic distribution and vaguely defined epidemiology of this novel pathogen have created an urgent need for effective public health countermeasures, including safe and effective treatment strategies. Despite the relatively few numbers of cases to date, research and development of MERS-CoV therapeutic candidates is advancing quickly. This review surveys the landscape of these efforts and assesses their potential for use in affected populations.",,"Modjarrad, Kayvon",J Virus Erad.; 2(1):1-4,,,True
0f90aed025cdf162b89014244740266ce67a3f47,PMC,Trends in Incident and Recurrent Rates of First-Ever Ischemic Stroke in Taiwan between 2000 and 2011,http://dx.doi.org/10.5853/jos.2015.01326,PMC4747065,26687123,CC BY-NC,"BACKGROUND AND PURPOSE: The burden of stroke is comparatively greater in Asian countries than in the Western world. While there has been a documented recent decline in the incidence of stroke in several Western nations due to better risk factor management, much less is known about the nature and trajectory of stroke in Asia over the last decade. The objective of this study was to explore risk factors, medication use, incidence, and one-year recurrence of stroke in Taiwan. METHODS: We conducted a nationwide cohort study by reviewing all hospitalized patients (≥ 18 years) with a primary diagnosis of ischemic stroke between 2001 and 2011 from Taiwan National Health Insurance Research Database. RESULTS: A total of 291,381 first-ever ischemic stroke patients were enrolled between 2000 and 2011. The average age was about 70 years and approximately 58.6% of them were men. While prevalence of diabetes mellitus and hyperlipidemia, as well as use of statins, antiplatelet agents, and oral anticoagulant agents for atrial fibrillation significantly increased; incidence (142.3 vs. 129.5 per 100,000 in 2000 and 2011, respectively) and one-year recurrence (9.6% vs. 7.8% in 2000 and 2011, respectively) of stroke declined during this period of time. CONCLUSIONS: Over the last decade in Taiwan, rates of primary ischemic stroke and one-year recurrent stroke decreased by 9% and 18% respectively.",2016 Jan 17,"['Lee, Meng', 'Wu, Yi-Ling', 'Ovbiagele, Bruce']",J Stroke,,,True
04421db3d34e7fd7c7486d66d21b34978a1fb362,PMC,Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide,http://dx.doi.org/10.1084/jem.20150712,PMC4749923,26755706,CC BY-NC-SA,"Type I interferon (IFN) is crucial in host antiviral defense. Previous studies have described the pleiotropic role of type I IFNs on innate and adaptive immune cells during viral infection. Here, we demonstrate that natural killer (NK) cells from mice lacking the type I IFN-α receptor (Ifnar(−/−)) or STAT1 (which signals downstream of IFNAR) are defective in expansion and memory cell formation after mouse cytomegalovirus (MCMV) infection. Despite comparable proliferation, Ifnar(−/−) NK cells showed diminished protection against MCMV infection and exhibited more apoptosis compared with wild-type NK cells. Furthermore, we show that Ifnar(−/−) NK cells express increased levels of NK group 2 member D (NKG2D) ligands during viral infection and are susceptible to NK cell–mediated fratricide in a perforin- and NKG2D-dependent manner. Adoptive transfer of Ifnar(−/−) NK cells into NK cell–deficient mice reverses the defect in survival and expansion. Our study reveals a novel type I IFN–dependent mechanism by which NK cells evade mechanisms of cell death after viral infection.",2016 Feb 8,"['Madera, Sharline', 'Rapp, Moritz', 'Firth, Matthew A.', 'Beilke, Joshua N.', 'Lanier, Lewis L.', 'Sun, Joseph C.']",J Exp Med,,,True
8a5ad2d005613e6fca5b2a3d14e7e523e072ee4e,PMC,Legal Issues in Quarantine and Isolation for Control of Emerging Infectious Diseases,http://dx.doi.org/10.3961/jpmph.16.009,PMC4750511,26841880,CC BY-NC,"The Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 has drawn public attention regarding the legal regulation of infectious disease control in Korea. This paper discusses the interpretive and legislative concerns regarding the Infectious Disease Prevention and Control Act, its ordinance and enforcement regulations, as well as public statements from the relevant administrative agency. Future improvements are also proposed.",2016 Jan 29,"Kim, Cheonsoo",J Prev Med Public Health,,,False
953ce6c11451011ff271b730ac3d2bdadda75830,PMC,Ethical Perspectives on the Middle East Respiratory Syndrome Coronavirus Epidemic in Korea,http://dx.doi.org/10.3961/jpmph.16.013,PMC4750516,26841881,CC BY-NC,"Ethical considerations are essential in planning for and responding to outbreaks of infectious diseases. During the outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in the Republic of Korea in 2015, serious challenges emerged regarding important ethical issues, such as transparency and the protection of privacy. The development of bioethics in Korea has been influenced by individualistic perspectives applied in clinical contexts, leading to a paucity of ethical perspectives relevant to population-level phenomena such as outbreaks. Alternative theories of public health ethics include the perspectives of relational autonomy and the patient as victim and vector. Public health actions need to incorporate clear and systematic procedures founded upon ethical principles. The MERS-CoV epidemic in Korea created significant public support for more aggressive early interventions in future outbreaks. This trend makes it all the more imperative for ethical principles and procedures to be implemented in future planning and responses to outbreaks in order to promote perceptions of legitimacy and civic participation.",2016 Jan 29,"Kim, Ock-Joo",J Prev Med Public Health,,,True
9c6e96b1ba2b2e3a95621656bbf142cc11eb955a,PMC,Prevalence and phylogenetic analysis of canine kobuviruses in diarrhoetic dogs in northeast China,http://dx.doi.org/10.1292/jvms.15-0414,PMC4751110,26256044,CC BY-NC-ND,"Canine kobuviruses (CaKVs) are newly recognized picornaviruses that have been recently detected in dogs in the U.S.A., Italy, U.K., the Republic of Korea and Tanzania. To trace the evolution of CaKV strains, a total of 201 fecal samples from rectal swabs of diarrheic dogs, which were obtained from May 2014 to April 2015 in northeast China, were detected by reverse transcription-PCR targeting a partial (504 bp) fragment of the 3D gene. Furthermore, a phylogenetic analysis of the CaKV strains identified in northeast China was conducted based on the partial 3D gene sequence. The results indicated that 36 fecal samples (17.91%, 36/201) were positive for CaKV, in which the co-infection rates of canine coronavirus, canine parvovirus-2 and canine bocavirus were 58.33%, 41.67%, and 11.11%, respectively. Sequence comparison of the partial 3D gene revealed nucleotide homologies of 94.4–100%, 95.6–98.6%, 94.3–97.6%, 94.4–96.3% and 93.3–95.1% within the 36 Chinese CaKV strains, and between the 36 Chinese CaKV strains and four CaKV reference strains from South Korea, Italy, U.S.A. and Tanzania, respectively. A phylogenetic tree revealed that the 36 Chinese CaKV strains formed one specific CaKV lineage with CaKVs that have recently been identified in other countries. The 36 Chinese CaKV strains were closely related to CaKV reference strains from Asia and Europe, but differed genetically from CaKV reference strains from North America and Africa. This study provides evidence that CaKVs circulate in diarrhoetic dogs in China and that they exhibit substantial genetic diversity and high co-infection rates with other enteric viruses.",2016 Jan 7,"['LI, Chunqiu', 'WEI, Shan', 'GUO, Donghua', 'WANG, Zhihui', 'GENG, Yufei', 'WANG, Enyu', 'ZHAO, Xiwen', 'SU, Mingjun', 'WANG, Xinyu', 'SUN, Dongbo']",J Vet Med Sci,,,True
5d352d8eaadb17dc1ed4cd7501e3533d366c939c,PMC,The requirement of environmental acidification for Ibaraki virus infection to host cells,http://dx.doi.org/10.1292/jvms.15-0222,PMC4751137,26321298,CC BY-NC-ND,"The effect of environmental acidification on Ibaraki virus (IBAV) infection was tested using endosomal inhibitory chemicals and low pH treatment. Treatment of target cells with endosomal inhibitors significantly decreased the progeny virus production. IBAV outer capsid proteins, VP5 and VP2, were removed from virion when purified IBAV was exposed to low pH environment. Further experiment showed that the exposure to low pH buffer facilitated IBAV infection when the cellular endosomal pathway was impaired by bafilomycin A1. Results obtained in this study suggest that acidic environment is essential to initiate IBAV infection.",2016 Jan 28,"['TSURUTA, Yuya', 'SHIBUTANI, Shusaku T.', 'WATANABE, Rie', 'IWATA, Hiroyuki']",J Vet Med Sci,,,True
748d4c57fe1acc8d9d97cf574f7dea5296f9386c,PMC,Direct Visualization of Ebola Virus Fusion Triggering in the Endocytic Pathway,http://dx.doi.org/10.1128/mBio.01857-15,PMC4752599,26861015,CC BY-NC-SA,"Ebola virus (EBOV) makes extensive and intricate use of host factors in the cellular endosomal/lysosomal pathway to release its genome into the cytoplasm and initiate infection. Following viral internalization into endosomes, host cysteine proteases cleave the EBOV fusion glycoprotein (GP) to unmask the binding site for its intracellular receptor, the cholesterol transporter Niemann-Pick C1 (NPC1). GP-NPC1 interaction is required for viral entry. Despite these and other recent discoveries, late events in EBOV entry following GP-NPC1 binding and culminating in GP-catalyzed fusion between viral and cellular lipid bilayers remain enigmatic. A mechanistic understanding of EBOV membrane fusion has been hampered by the failure of previous efforts to reconstitute fusion in vitro or at the cell surface. This report describes an assay to monitor initial steps directly in EBOV membrane fusion—triggering of GP and virus-cell lipid mixing—by single virions in live cells. Fusogenic triggering of GP occurs predominantly in Rab7-positive (Rab7(+)) endosomes, absolutely requires interaction between proteolytically primed GP and NPC1, and is blocked by key GP-specific neutralizing antibodies with therapeutic potential. Unexpectedly, cysteine protease inhibitors do not inhibit lipid mixing by virions bearing precleaved GP, even though they completely block cytoplasmic entry by these viruses, as shown previously. These results point to distinct cellular requirements for different steps in EBOV membrane fusion and suggest a model in which host cysteine proteases are dispensable for GP fusion triggering after NPC1 binding but are required for the formation of fusion pores that permit genome delivery.",2016 Feb 9,"['Spence, Jennifer S.', 'Krause, Tyler B.', 'Mittler, Eva', 'Jangra, Rohit K.', 'Chandran, Kartik']",mBio,,,True
358d351a51c6f7f9ddb86ea3fb468c7fdc601e3d,PMC,The Membrane Protein of Severe Acute Respiratory Syndrome Coronavirus Functions as a Novel Cytosolic Pathogen-Associated Molecular Pattern To Promote Beta Interferon Induction via a Toll-Like-Receptor-Related TRAF3-Independent Mechanism,http://dx.doi.org/10.1128/mBio.01872-15,PMC4752600,26861016,CC BY-NC-SA,"Most of the intracellular pattern recognition receptors (PRRs) reside in either the endolysosome or the cytoplasm to sense pathogen-derived RNAs, DNAs, or synthetic analogs of double-stranded RNA (dsRNA), such as poly(I:C). However, it remains elusive whether or not a pathogen-derived protein can function as a cytosolic pathogen-associated molecular pattern (PAMP). In this study, we demonstrate that delivering the membrane gene of severe acute respiratory syndrome coronavirus (SARS-CoV) into HEK293T, HEK293ET, and immobilized murine bone marrow-derived macrophage (J2-Mφ) cells significantly upregulates beta interferon (IFN-β) production. Both NF-κB and TBK1-IRF3 signaling cascades are activated by M gene products. M protein rather than M mRNA is responsible for M-mediated IFN-β induction that is preferentially associated with the activation of the Toll-like receptor (TLR) adaptor proteins MyD88, TIRAP, and TICAM2 but not the RIG-I signaling cascade. Blocking the secretion of M protein by brefeldin A (BFA) failed to reverse the M-mediated IFN-β induction. The antagonist of both TLR2 and TLR4 did not impede M-mediated IFN-β induction, indicating that the driving force for the activation of IFN-β production was generated from inside the cells. Inhibition of TRAF3 expression by specific small interfering RNA (siRNA) did not prevent M-mediated IFN-β induction. SARS-CoV pseudovirus could induce IFN-β production in an M rather than M(V68A) dependent manner, since the valine-to-alanine alteration at residue 68 in M protein markedly inhibited IFN-β production. Overall, our study indicates for the first time that a pathogen-derived protein is able to function as a cytosolic PAMP to stimulate type I interferon production by activating a noncanonical TLR signaling cascade in a TRAF3-independent manner.",2016 Feb 9,"['Wang, Yi', 'Liu, Li']",mBio,,,True
622504276a8cd63e834d19f7b3c26ca4c2bbcb40,PMC,Interleukin‐10 is a critical regulator of white matter lesion containment following viral induced demyelination,http://dx.doi.org/10.1002/glia.22880,PMC4755156,26132901,CC BY-NC-ND,"Neurotropic coronavirus induces an acute encephalomyelitis accompanied by focal areas of demyelination distributed randomly along the spinal column. The initial areas of demyelination increase only slightly after the control of infection. These circumscribed focal lesions are characterized by axonal sparing, myelin ingestion by macrophage/microglia, and glial scars associated with hypertrophic astrocytes, which proliferate at the lesion border. Accelerated virus control in mice lacking the anti‐inflammatory cytokine IL‐10 was associated with limited initial demyelination, but low viral mRNA persistence similar to WT mice and declining antiviral cellular immunity. Nevertheless, lesions exhibited sustained expansion providing a model of dysregulated white matter injury temporally remote from the acute CNS insult. Expanding lesions in the absence of IL‐10 are characterized by sustained microglial activation and partial loss of macrophage/microglia exhibiting an acquired deactivation phenotype. Furthermore, IL‐10 deficiency impaired astrocyte organization into mesh like structures at the lesion borders, but did not prevent astrocyte hypertrophy. The formation of discrete foci of demyelination in IL‐10 sufficient mice correlated with IL‐10 receptor expression exclusively on astrocytes in areas of demyelination suggesting a critical role for IL‐10 signaling to astrocytes in limiting expansion of initial areas of white matter damage. GLIA 2015;63:2106–2120",2015 Nov 30,"['Puntambekar, Shweta S.', 'Hinton, David R.', 'Yin, Xinghua', 'Savarin, Carine', 'Bergmann, Cornelia C.', 'Trapp, Bruce D.', 'Stohlman, Stephen A.']",Glia,,,True
0bcc4d843bd37ae1c8623e45dab6fff11263f798,PMC,Stable long‐term cultures of self‐renewing B cells and their applications,http://dx.doi.org/10.1111/imr.12395,PMC4755196,26864105,CC BY-NC-ND,"Monoclonal antibodies are essential therapeutics and diagnostics in a large number of diseases. Moreover, they are essential tools in all sectors of life sciences. Although the great majority of monoclonal antibodies currently in use are of mouse origin, the use of human B cells to generate monoclonal antibodies is increasing as new techniques to tap the human B cell repertoire are rapidly emerging. Cloned lines of immortalized human B cells are ideal sources of monoclonal antibodies. In this review, we summarize our studies to the regulation of the replicative life span, differentiation, and maturation of B cells that led to the development of a platform that uses immortalization of human B cells by in vitro genetic modification for antibody development. We describe a number of human antibodies that were isolated using this platform and the application of the technique in other species. We also discuss the use of immortalized B cells as antigen‐presenting cells for the discovery of tumor neoantigens.",2016 Mar 10,"['Kwakkenbos, Mark J.', 'van Helden, Pauline M.', 'Beaumont, Tim', 'Spits, Hergen']",Immunol Rev,,,True
8e101b19cc15410540e85ce7f2e77208e3c411d5,PMC,Severe Acute Respiratory Distress Syndrome after Bilateral Total Knee Replacement,http://dx.doi.org/10.4103/0366-6999.168083,PMC4756890,26521804,CC BY-NC-SA,,2015 Nov 5,"['Ma, Lu-Lu', 'Yu, Xue-Rong']",Chin Med J (Engl),,,True
5c49361dc3511c5c14855745fedcbafc97d9ca96,PMC,One Health and EcoHealth: the same wine in different bottles?,http://dx.doi.org/10.3402/iee.v6.30978,PMC4761681,26899935,CC BY-NC,,2016 Feb 17,"['Roger, François', 'Caron, Alexandre', 'Morand, Serge', 'Pedrono, Miguel', 'de Garine-Wichatitsky, Michel', 'Chevalier, Veronique', 'Tran, Annelise', 'Gaidet, Nicolas', 'Figuié, Muriel', 'de Visscher, Marie-Noël', 'Binot, Aurélie']",Infect Ecol Epidemiol,,,True
8d811ab0308d0b39edc268e8b0dd87bd4c3eca26,PMC,"RNA Viruses: RNA Roles in Pathogenesis, Coreplication and Viral Load",http://dx.doi.org/10.2174/1389202916666150707160613,PMC4763971,27047253,CC BY-NC,"The review intends to present and recapitulate the current knowledge on the roles and importance of regulatory RNAs, such as microRNAs and small interfering RNAs, RNA binding proteins and enzymes processing RNAs or activated by RNAs, in cells infected by RNA viruses. The review focuses on how non-coding RNAs are involved in RNA virus replication, pathogenesis and host response, especially in retroviruses HIV, with examples of the mechanisms of action, transcriptional regulation, and promotion of increased stability of their targets or their degradation.",2015 Oct,"['Poltronieri, Palmiro', 'Sun, Binlian', 'Mallardo, Massimo']",Curr Genomics,,,True
5667ab8a8565a702defd98b5736e32a3bb9c5ad4,PMC,"Nonproliferative and Proliferative Lesions of the Gastrointestinal Tract, Pancreas and Salivary Glands of the Rat and Mouse",http://dx.doi.org/10.1293/tox.29.1S,PMC4765498,26973378,CC BY-NC-ND,"The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) project is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature and diagnostic criteria for nonproliferative and proliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature and diagnostic criteria for classifying lesions in the digestive system including the salivary glands and the exocrine pancreas of laboratory rats and mice. Most lesions are illustrated by color photomicrographs. The standardized nomenclature, the diagnostic criteria, and the photomicrographs are also available electronically on the Internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and age related lesions as well as lesions induced by exposure to test items. Relevant infectious and parasitic lesions are included as well. A widely accepted and utilized international harmonization of nomenclature and diagnostic criteria for the digestive system will decrease misunderstandings among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.",2016 Feb 13,"['Nolte, Thomas', 'Brander-Weber, Patricia', 'Dangler, Charles', 'Deschl, Ulrich', 'Elwell, Michael R.', 'Greaves, Peter', 'Hailey, Richard', 'Leach, Michael W.', 'Pandiri, Arun R.', 'Rogers, Arlin', 'Shackelford, Cynthia C.', 'Spencer, Andrew', 'Tanaka, Takuji', 'Ward, Jerrold M.']",J Toxicol Pathol,,,True
879df084e06fcce1980e3f73c36748068b39f049,PMC,Ebola or Not? Evaluating the Ill Traveler From Ebola-Affected Countries in West Africa,http://dx.doi.org/10.1093/ofid/ofw005,PMC4766384,26925428,CC BY-NC-ND,"Background. The 2014–2015 Ebola epidemic in West Africa had global impact beyond the primarily affected countries of Guinea, Liberia, and Sierra Leone. Other countries, including the United States, encountered numerous patients who arrived from highly affected countries with fever or other signs or symptoms consistent with Ebola virus disease (EVD). Methods. We describe our experience evaluating 25 travelers who met the US Centers for Disease Control and Prevention case definition for a person under investigation (PUI) for EVD from July 20, 2014 to January 28, 2015. All patients were triaged and evaluated under the guidance of institutional protocols to the emergency department, outpatient tropical medicine clinic, or Emory's Ebola treatment unit. Strict attention to infection control and early involvement of public health authorities guided the safe evaluation of these patients. Results. None were diagnosed with EVD. Respiratory illnesses were common, and 8 (32%) PUI were confirmed to have influenza. Four patients (16%) were diagnosed with potentially life-threatening infections or conditions, including 3 with Plasmodium falciparum malaria and 1 with diabetic ketoacidosis. Conclusions. In addition to preparing for potential patients with EVD, Ebola assessment centers should consider other life-threatening conditions requiring urgent treatment, and travelers to affected countries should be strongly advised to seek pretravel counseling. Furthermore, attention to infection control in all aspects of PUI evaluation is paramount and has presented unique challenges. Lessons learned from our evaluation of potential patients with EVD can help inform preparations for future outbreaks of highly pathogenic communicable diseases.",2016 Jan 18,"['Fairley, Jessica K.', 'Kozarsky, Phyllis E.', 'Kraft, Colleen S.', 'Guarner, Jeannette', 'Steinberg, James P.', 'Anderson, Evan', 'Jacob, Jesse T.', 'Meloy, Patrick', 'Gillespie, Darria', 'Espinoza, Tamara R.', 'Isakov, Alexander', 'Vanairsdale, Sharon', 'Baker, Esther', 'Wu, Henry M.']",Open Forum Infect Dis,,,True
11217ee4e2bcf58f21011db8ff3d166aad2691ca,PMC,How and Why Overcome the Impediments to Resolution: Lessons from rhinolophid and hipposiderid Bats,http://dx.doi.org/10.1093/molbev/msu329,PMC4769323,25433366,CC BY-NC,"The phylogenetic and taxonomic relationships among the Old World leaf-nosed bats (Hipposideridae) and the closely related horseshoe bats (Rhinolophidae) remain unresolved. In this study, we generated a novel approximately 10-kb molecular data set of 19 nuclear exon and intron gene fragments for 40 bat species to elucidate the phylogenetic relationships within the families Rhinolophidae and Hipposideridae. We estimated divergence times and explored potential reasons for any incongruent phylogenetic signal. We demonstrated the effects of outlier taxa and genes on phylogenetic reconstructions and compared the relative performance of intron and exon data to resolve phylogenetic relationships. Phylogenetic analyses produced a well-resolved phylogeny, supporting the familial status of Hipposideridae and demonstrated the paraphyly of the largest genus, Hipposideros. A fossil-calibrated timetree and biogeographical analyses estimated that Rhinolophidae and Hipposideridae diverged in Africa during the Eocene approximately 42 Ma. The phylogram, the timetree, and a unique retrotransposon insertion supported the elevation of the subtribe Rhinonycterina to family level and which is diagnosed herein. Comparative analysis of diversification rates showed that the speciose genera Rhinolophus and Hipposideros underwent diversification during the Mid-Miocene Climatic Optimum. The intron versus exon analyses demonstrated the improved nodal support provided by introns for our optimal tree, an important finding for large-scale phylogenomic studies, which typically rely on exon data alone. With the recent outbreak of Middle East respiratory syndrome, caused by a novel coronavirus, the study of these species is urgent as they are considered the natural reservoir for emergent severe acute respiratory syndrome (SARS)-like coronaviruses. It has been shown that host phylogeny is the primary factor that determines a virus’s persistence, replicative ability, and can act as a predictor of new emerging disease. Therefore, this newly resolved phylogeny can be used to direct future assessments of viral diversity and to elucidate the origin and development of SARS-like coronaviruses in mammals.",2015 Feb 29,"['Foley, Nicole M.', 'Thong, Vu Dinh', 'Soisook, Pipat', 'Goodman, Steven M.', 'Armstrong, Kyle N.', 'Jacobs, David S.', 'Puechmaille, Sébastien J.', 'Teeling, Emma C.']",Mol Biol Evol,,,True
75275e1adbc2a3dcb78893dd1cf92d7fcf2915cc,PMC,"Identifying determinants of heterogeneous transmission dynamics of the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea, 2015: a retrospective epidemiological analysis",http://dx.doi.org/10.1136/bmjopen-2015-009936,PMC4769415,26908522,CC BY-NC,"OBJECTIVES: To investigate the heterogeneous transmission patterns of Middle East respiratory syndrome (MERS) in the Republic of Korea, with a particular focus on epidemiological characteristics of superspreaders. DESIGN: Retrospective epidemiological analysis. SETTING: Multiple healthcare facilities of secondary and tertiary care centres in an urban setting. PARTICIPANTS: A total of 185 laboratory-confirmed cases with partially known dates of illness onset and most likely sources of infection. PRIMARY AND SECONDARY OUTCOME MEASURES: Superspreaders were identified using the transmission tree. The reproduction number, that is, the average number of secondary cases produced by a single primary case, was estimated as a function of time and according to different types of hosts. RESULTS: A total of five superspreaders were identified. The reproduction number throughout the course of the outbreak was estimated at 1.0 due to reconstruction of the transmission tree, while the variance of secondary cases generated by a primary case was 52.1. All of the superspreaders involved in this outbreak appeared to have generated a substantial number of contacts in multiple healthcare facilities (association: p<0.01), generating on average 4.0 (0.0–8.6) and 28.6 (0.0–63.9) secondary cases among patients who visited multiple healthcare facilities and others. The time-dependent reproduction numbers declined substantially below the value of 1 on and after 13 June 2015. CONCLUSIONS: Superspreaders who visited multiple facilities drove the epidemic by generating a disproportionate number of secondary cases. Our findings underscore the need to limit the contacts in healthcare settings. Contact tracing efforts could assist early laboratory testing and diagnosis of suspected cases.",2016 Feb 22,"['Nishiura, Hiroshi', 'Endo, Akira', 'Saitoh, Masaya', 'Kinoshita, Ryo', 'Ueno, Ryo', 'Nakaoka, Shinji', 'Miyamatsu, Yuichiro', 'Dong, Yueping', 'Chowell, Gerardo', 'Mizumoto, Kenji']",BMJ Open,,,True
1315bcaaeb74c9aaec8924b69babe2f257e56f42,PMC,"Identifying determinants of heterogeneous transmission dynamics of the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea, 2015: a retrospective epidemiological analysis",http://dx.doi.org/10.1136/bmjopen-2015-009936,PMC4769415,26908522,CC BY-NC,"OBJECTIVES: To investigate the heterogeneous transmission patterns of Middle East respiratory syndrome (MERS) in the Republic of Korea, with a particular focus on epidemiological characteristics of superspreaders. DESIGN: Retrospective epidemiological analysis. SETTING: Multiple healthcare facilities of secondary and tertiary care centres in an urban setting. PARTICIPANTS: A total of 185 laboratory-confirmed cases with partially known dates of illness onset and most likely sources of infection. PRIMARY AND SECONDARY OUTCOME MEASURES: Superspreaders were identified using the transmission tree. The reproduction number, that is, the average number of secondary cases produced by a single primary case, was estimated as a function of time and according to different types of hosts. RESULTS: A total of five superspreaders were identified. The reproduction number throughout the course of the outbreak was estimated at 1.0 due to reconstruction of the transmission tree, while the variance of secondary cases generated by a primary case was 52.1. All of the superspreaders involved in this outbreak appeared to have generated a substantial number of contacts in multiple healthcare facilities (association: p<0.01), generating on average 4.0 (0.0–8.6) and 28.6 (0.0–63.9) secondary cases among patients who visited multiple healthcare facilities and others. The time-dependent reproduction numbers declined substantially below the value of 1 on and after 13 June 2015. CONCLUSIONS: Superspreaders who visited multiple facilities drove the epidemic by generating a disproportionate number of secondary cases. Our findings underscore the need to limit the contacts in healthcare settings. Contact tracing efforts could assist early laboratory testing and diagnosis of suspected cases.",2016 Feb 22,"['Nishiura, Hiroshi', 'Endo, Akira', 'Saitoh, Masaya', 'Kinoshita, Ryo', 'Ueno, Ryo', 'Nakaoka, Shinji', 'Miyamatsu, Yuichiro', 'Dong, Yueping', 'Chowell, Gerardo', 'Mizumoto, Kenji']",BMJ Open,,,False
c5e6b31b9d1b7d0b62564566e8deaf48a03a8f32,PMC,Korean Society for Laboratory Medicine Practice Guidelines for the Molecular Diagnosis of Middle East Respiratory Syndrome During an Outbreak in Korea in 2015,http://dx.doi.org/10.3343/alm.2016.36.3.203,PMC4773259,26915607,CC BY-NC,"For two months between May and July 2015, a nationwide outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) occurred in Korea. On June 3, 2015, the Korean Society for Laboratory Medicine (KSLM) launched a MERS-CoV Laboratory Response Task Force (LR-TF) to facilitate clinical laboratories to set up the diagnosis of MERS-CoV infection. Based on the WHO interim recommendations, the Centers for Disease Control and Prevention of United States guidelines for MERS-CoV laboratory testing, and other available resources, the KSLM MERS-CoV LR-TF provided the first version of the laboratory practice guidelines for the molecular diagnosis of MERS-CoV to the clinical laboratories on June 12, 2015. The guidelines described here are an updated version that includes case definition, indications for testing, specimen type and protocols for specimen collection, specimen packing and transport, specimen handling and nucleic acid extraction, molecular detection of MERS-CoV, interpretation of results and reporting, and laboratory safety. The KSLM guidelines mainly focus on the molecular diagnosis of MERS-CoV, reflecting the unique situation in Korea and the state of knowledge at the time of publication.",2016 May 23,"['Ki, Chang-Seok', 'Lee, Hyukmin', 'Sung, Heungsup', 'Kim, Sinyoung', 'Seong, Moon-Woo', 'Yong, Dongeun', 'Kim, Jae-Seok', 'Lee, Mi-Kyung', 'Kim, Mi-Na', 'Choi, Jong-Rak', 'Kim, Jeong-Ho', None]",Ann Lab Med,,,True
663f66630b5b3b7914dcbcaed555d5865da925dd,PMC,External Quality Assessment of MERS-CoV Molecular Diagnostics During the 2015 Korean Outbreak,http://dx.doi.org/10.3343/alm.2016.36.3.230,PMC4773263,26915611,CC BY-NC,"BACKGROUND: The largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection outside Middle East Asia in 2015 has necessitated the rapid expansion of laboratories that conduct MERS-CoV molecular testing in Korea, together with external quality assessment (EQA) to evaluate the assays used. METHODS: The EQA program consisted of two phases; self-validation and blind assessment. For the first EQA phase, in vitro transcribed upstream region of the envelope gene (upE) and the open reading frame (ORF)1a RNAs were used at a concentration of 1,000 copies/µL. The test panel for the second EQA phase consisted of RNA extracts from three samples, which were obtained from two MERS-CoV positive patients and one MERS-CoV negative patient. RESULTS: The first EQA phase results for 46 participants showed a linear relationship between the threshold cycle (C(T)) values of RNA materials and the logarithmic concentrations for both upE and ORF1a gene targets (R(2)=0.73 and 0.75, respectively). The mean C(T) value for each concentration was different depending on which commercial kit was used for the assay. Among the three commonly used kits, PowerChek MERS Real-Time PCR kit (KogeneBiotech, Korea) showed the lowest C(T) values at all concentrations of upE and most concentrations of ORF1a. The second EQA phase results for 47 participants were 100% correct for all tested samples. CONCLUSIONS: This EQA survey demonstrates that the MERS-CoV molecular testing performed in Korea during the 2015 outbreak is of robust capability. However, careful establishment and validation of a cut-off value are recommended to ensure good analytical sensitivity.",2016 May 23,"['Seong, Moon-Woo', 'Lee, Seung Jun', 'Cho, Sung Im', 'Ko, Kyungphil', 'Kim, Mi-Na', 'Sung, Heungsub', 'Kim, Jae-Seok', 'Ahn, Ji Soo', 'Yu, Byung Su', 'Kim, Taek Soo', 'Kim, Eui Chong', 'Park, Sung Sup']",Ann Lab Med,,,True
e2a428dc2e6fdc4ef6f6c9537409b90f106639f4,PMC,A Disease Around the Corner,http://dx.doi.org/10.1016/j.phrp.2016.02.001,PMC4776264,26981335,CC BY-NC-ND,,2016 Feb 24,"['Cho, Hae-Wol', 'Chu, Chaeshin']",Osong Public Health Res Perspect,,,False
03ad1cf472c9636fceb1b800c553fde73724e349,PMC,The Characteristics of Middle Eastern Respiratory Syndrome Coronavirus Transmission Dynamics in South Korea,http://dx.doi.org/10.1016/j.phrp.2016.01.001,PMC4776270,26981343,CC BY-NC-ND,"OBJECTIVES: The outbreak of Middle Eastern respiratory syndrome coronavirus (MERS-CoV) was one of the major events in South Korea in 2015. In particular, this study pays attention to formulating a mathematical model for MERS transmission dynamics and estimating transmission rates. METHODS: Incidence data of MERS-CoV from the government authority was analyzed for the first aim and a mathematical model was built and analyzed for the second aim of the study. A mathematical model for MERS-CoV transmission dynamics is used to estimate the transmission rates in two periods due to the implementation of intensive interventions. RESULTS: Using the estimates of the transmission rates, the basic reproduction number was estimated in two periods. Due to the superspreader, the basic reproduction number was very large in the first period; however, the basic reproduction number of the second period has reduced significantly after intensive interventions. CONCLUSION: It turned out to be the intensive isolation and quarantine interventions that were the most critical factors that prevented the spread of the MERS outbreak. The results are expected to be useful to devise more efficient intervention strategies in the future.",2016 Feb 18,"['Kim, Yunhwan', 'Lee, Sunmi', 'Chu, Chaeshin', 'Choe, Seoyun', 'Hong, Saeme', 'Shin, Youngseo']",Osong Public Health Res Perspect,,,False
c97243d65788222d1cf09203e27ae04deaf0ef1c,PMC,Bacterial–viral load and the immune response in stable and exacerbated COPD: significance and therapeutic prospects,http://dx.doi.org/10.2147/COPD.S93398,PMC4780195,27042037,CC BY-NC,"Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and an abnormal inflammatory response of the lung. Bacteria and viruses are a major cause of COPD exacerbations and may contribute to COPD progression by perpetuating the inflammatory response in the airways. Bacterial variety diminishes with increasing COPD severity. Respiratory viruses can colonize the lower respiratory tract in stable COPD, altering the respiratory microbiome and facilitating secondary bacterial infections. In this review, we present the most updated information about the role of bacteria and viruses in stable and exacerbated COPD. In our opinion, to optimize therapeutic strategies, the dynamic events involving bacterial–viral infections and related immune response in COPD phenotypes need to be better clarified. Our paper would address these points that we consider of great importance for the clinical management of COPD.",2016 Mar 1,"['D’Anna, Silvestro Ennio', 'Balbi, Bruno', 'Cappello, Francesco', 'Carone, Mauro', 'Di Stefano, Antonino']",Int J Chron Obstruct Pulmon Dis,,,True
3bbbbc7190599b47616269323cfbd3659d9dc420,PMC,Bacterial Artificial Chromosomes: A Functional Genomics Tool for the Study of Positive-strand RNA Viruses,http://dx.doi.org/10.3791/53164,PMC4780872,26780115,CC BY-NC-ND,"Reverse genetics, an approach to rescue infectious virus entirely from a cloned cDNA, has revolutionized the field of positive-strand RNA viruses, whose genomes have the same polarity as cellular mRNA. The cDNA-based reverse genetics system is a seminal method that enables direct manipulation of the viral genomic RNA, thereby generating recombinant viruses for molecular and genetic studies of both viral RNA elements and gene products in viral replication and pathogenesis. It also provides a valuable platform that allows the development of genetically defined vaccines and viral vectors for the delivery of foreign genes. For many positive-strand RNA viruses such as Japanese encephalitis virus (JEV), however, the cloned cDNAs are unstable, posing a major obstacle to the construction and propagation of the functional cDNA. Here, the present report describes the strategic considerations in creating and amplifying a genetically stable full-length infectious JEV cDNA as a bacterial artificial chromosome (BAC) using the following general experimental procedures: viral RNA isolation, cDNA synthesis, cDNA subcloning and modification, assembly of a full-length cDNA, cDNA linearization, in vitro RNA synthesis, and virus recovery. This protocol provides a general methodology applicable to cloning full-length cDNA for a range of positive-strand RNA viruses, particularly those with a genome of >10 kb in length, into a BAC vector, from which infectious RNAs can be transcribed in vitro with a bacteriophage RNA polymerase.",2015 Dec 29,"['Yun, Sang-Im', 'Song, Byung-Hak', 'Kim, Jin-Kyoung', 'Lee, Young-Min']",J Vis Exp,,,True
85b24dcdfc025236507fb1a3bdbb8eb816bbef92,PMC,Regression of established renal cell carcinoma in nude mice using lentivirus-transduced human T cells expressing a human anti-CAIX chimeric antigen receptor,http://dx.doi.org/10.1038/mto.2014.3,PMC4782938,27119093,CC BY-NC-ND,"Carbonic anhydrase IX (CAIX) is a tumor-associated antigen and marker of hypoxia that is overexpressed on > 90% of clear-cell type renal cell carcinoma (RCC) but not on neighboring normal kidney tissue. Here, we report on the construction of two chimeric antigen receptors (CARs) that utilize a carbonic anhydrase (CA) domain mapped, human single chain antibody (scFv G36) as a targeting moiety but differ in their capacity to provide costimulatory signaling for optimal T cell proliferation and tumor cell killing. The resulting anti-CAIX CARs were expressed on human primary T cells via lentivirus transduction. CAR-transduced T cells (CART cells) expressing second-generation G36-CD28-TCRζ exhibited more potent in vitro antitumor effects on CAIX(+) RCC cells than first-generation G36-CD8-TCRζ including cytotoxicity, cytokine secretion, proliferation, and clonal expansion. Adoptive G36-CD28-TCRζ CART cell therapy combined with high-dose interleukin (IL)-2 injection also lead to superior regression of established RCC in nude mice with evidence of tumor cell apoptosis and tissue necrosis. These results suggest that the fully human G36-CD28-TCRζ CARs should provide substantial improvements over first-generation mouse anti-CAIX CARs in clinical use through reduced human anti-mouse antibody responses against the targeting scFv and administration of lower doses of T cells during CART cell therapy of CAIX(+) RCC.",2014 Dec 10,"['Lo, Agnes Shuk-Yee', 'Xu, Chen', 'Murakami, Akikazu', 'Marasco, Wayne A']",Mol Ther Oncolytics,,,True
e3db3c2e1b832030eda8db862a8eb2ab647c0528,PMC,Prevalence of canine coronavirus (CCoV) in dog in Japan: detection of CCoV RNA and retrospective serological analysis,http://dx.doi.org/10.1292/jvms.15-0347,PMC4785132,26460314,CC BY-NC-ND,"We collected rectal swabs from dogs in Japan during 2011 to 2014, and canine coronavirus (CCoV) nucleocapsid gene was detected by RT-PCR. The relationship between CCoV infection and the manifestation of diarrhea symptoms was investigated, and a correlation was noted (df=1, χ(2)=8.90, P<0.005). The types of CCoV detected in samples from CCoV-infected dogs were CCoV-I in 88.9% and CCoV-II in 7.4%, respectively. We retrospectively investigated the seroprevalence of CCoV-I in dogs in Japan during 1998 to 2006. The sera were tested with a neutralizing antibody test. In the absence of CCoV-I laboratory strain, we used feline coronavirus (FCoV)-I that shares high sequence homology in the S protein with CCoV-I. 77.7% of the sera were positive for neutralizing anti-FCoV-I antibodies.",2016 Feb 11,"['TAKANO, Tomomi', 'YAMASHITA, Saya', 'MURATA-OHKUBO, Michiko', 'SATOH, Kumi', 'DOKI, Tomoyoshi', 'HOHDATSU, Tsutomu']",J Vet Med Sci,,,True
3f50d334193fa8cd216e4c4166e43fb0c8109709,PMC,Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1038/cmi.2015.03,PMC4786625,25640653,CC BY-NC-ND,"Middle East respiratory syndrome (MERS), an emerging infectious disease caused by MERS coronavirus (MERS-CoV), has garnered worldwide attention as a consequence of its continuous spread and pandemic potential, making the development of effective vaccines a high priority. We previously demonstrated that residues 377–588 of MERS-CoV spike (S) protein receptor-binding domain (RBD) is a very promising MERS subunit vaccine candidate, capable of inducing potent neutralization antibody responses. In this study, we sought to identify an adjuvant that optimally enhanced the immunogenicity of S377–588 protein fused with Fc of human IgG (S377–588-Fc). Specifically, we compared several commercially available adjuvants, including Freund's adjuvant, aluminum, Monophosphoryl lipid A, Montanide ISA51 and MF59 with regard to their capacity to enhance the immunogenicity of this subunit vaccine. In the absence of adjuvant, S377–588-Fc alone induced readily detectable neutralizing antibody and T-cell responses in immunized mice. However, incorporating an adjuvant improved its immunogenicity. Particularly, among the aforementioned adjuvants evaluated, MF59 is the most potent as judged by its superior ability to induce the highest titers of IgG, IgG1 and IgG2a subtypes, and neutralizing antibodies. The addition of MF59 significantly augmented the immunogenicity of S377–588-Fc to induce strong IgG and neutralizing antibody responses as well as protection against MERS-CoV infection in mice, suggesting that MF59 is an optimal adjuvant for MERS-CoV RBD-based subunit vaccines.",2016 Mar 2,"['Zhang, Naru', 'Channappanavar, Rudragouda', 'Ma, Cuiqing', 'Wang, Lili', 'Tang, Jian', 'Garron, Tania', 'Tao, Xinrong', 'Tasneem, Sumaiya', 'Lu, Lu', 'Tseng, Chien-Te K', 'Zhou, Yusen', 'Perlman, Stanley', 'Jiang, Shibo', 'Du, Lanying']",Cell Mol Immunol,,,True
db9a1efb58ae0ed12ff657b5cc78fcc2615f0c73,PMC,Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia,http://dx.doi.org/10.1093/cid/civ1214,PMC4787606,26747825,CC BY-NC-ND,"Background. The frequent lack of a microbiological diagnosis in community-acquired pneumonia (CAP) impairs pathogen-directed antimicrobial therapy. This study assessed the use of comprehensive multibacterial, multiviral molecular testing, including quantification, in adults hospitalized with CAP. Methods. Clinical and laboratory data were collected for 323 adults with radiologically-confirmed CAP admitted to 2 UK tertiary care hospitals. Sputum (96%) or endotracheal aspirate (4%) specimens were cultured as per routine practice and also tested with fast multiplex real-time polymerase-chain reaction (PCR) assays for 26 respiratory bacteria and viruses. Bacterial loads were also calculated for 8 bacterial pathogens. Appropriate pathogen-directed therapy was retrospectively assessed using national guidelines adapted for local antimicrobial susceptibility patterns. Results. Comprehensive molecular testing of single lower respiratory tract (LRT) specimens achieved pathogen detection in 87% of CAP patients compared with 39% with culture-based methods. Haemophilus influenzae and Streptococcus pneumoniae were the main agents detected, along with a wide variety of typical and atypical pathogens. Viruses were present in 30% of cases; 82% of these were codetections with bacteria. Most (85%) patients had received antimicrobials in the 72 hours before admission. Of these, 78% had a bacterial pathogen detected by PCR but only 32% were culture-positive (P < .0001). Molecular testing had the potential to enable de-escalation in number and/or spectrum of antimicrobials in 77% of patients. Conclusions. Comprehensive molecular testing significantly improves pathogen detection in CAP, particularly in antimicrobial-exposed patients, and requires only a single LRT specimen. It also has the potential to enable early de-escalation from broad-spectrum empirical antimicrobials to pathogen-directed therapy.",2016 Apr 1,"['Gadsby, Naomi J.', 'Russell, Clark D.', 'McHugh, Martin P.', 'Mark, Harriet', 'Conway Morris, Andrew', 'Laurenson, Ian F.', 'Hill, Adam T.', 'Templeton, Kate E.']",Clin Infect Dis,,,True
8adc81255b4ba0eb48cbd7ddfe86f13959f39c7d,PMC,Discovery of an essential nucleotidylating activity associated with a newly delineated conserved domain in the RNA polymerase-containing protein of all nidoviruses,http://dx.doi.org/10.1093/nar/gkv838,PMC4787807,26304538,CC BY-NC,"RNA viruses encode an RNA-dependent RNA polymerase (RdRp) that catalyzes the synthesis of their RNA(s). In the case of positive-stranded RNA viruses belonging to the order Nidovirales, the RdRp resides in a replicase subunit that is unusually large. Bioinformatics analysis of this non-structural protein has now revealed a nidoviral signature domain (genetic marker) that is N-terminally adjacent to the RdRp and has no apparent homologs elsewhere. Based on its conservation profile, this domain is proposed to have nucleotidylation activity. We used recombinant non-structural protein 9 of the arterivirus equine arteritis virus (EAV) and different biochemical assays, including irreversible labeling with a GTP analog followed by a proteomics analysis, to demonstrate the manganese-dependent covalent binding of guanosine and uridine phosphates to a lysine/histidine residue. Most likely this was the invariant lysine of the newly identified domain, named nidovirus RdRp-associated nucleotidyltransferase (NiRAN), whose substitution with alanine severely diminished the described binding. Furthermore, this mutation crippled EAV and prevented the replication of severe acute respiratory syndrome coronavirus (SARS-CoV) in cell culture, indicating that NiRAN is essential for nidoviruses. Potential functions supported by NiRAN may include nucleic acid ligation, mRNA capping and protein-primed RNA synthesis, possibilities that remain to be explored in future studies.",2015 Sep 30,"['Lehmann, Kathleen C.', 'Gulyaeva, Anastasia', 'Zevenhoven-Dobbe, Jessika C.', 'Janssen, George\xa0M.\xa0C.', 'Ruben, Mark', 'Overkleeft, Hermen S.', 'van\xa0Veelen, Peter A.', 'Samborskiy, Dmitry\xa0V.', 'Kravchenko, Alexander A.', 'Leontovich, Andrey M.', 'Sidorov, Igor A.', 'Snijder, Eric J.', 'Posthuma, Clara C.', 'Gorbalenya, Alexander E.']",Nucleic Acids Res,,,True
67bcefd26515beef9b596c41af2932a6796ce961,PMC,Discovery of an essential nucleotidylating activity associated with a newly delineated conserved domain in the RNA polymerase-containing protein of all nidoviruses,http://dx.doi.org/10.1093/nar/gkv838,PMC4787807,26304538,CC BY-NC,"RNA viruses encode an RNA-dependent RNA polymerase (RdRp) that catalyzes the synthesis of their RNA(s). In the case of positive-stranded RNA viruses belonging to the order Nidovirales, the RdRp resides in a replicase subunit that is unusually large. Bioinformatics analysis of this non-structural protein has now revealed a nidoviral signature domain (genetic marker) that is N-terminally adjacent to the RdRp and has no apparent homologs elsewhere. Based on its conservation profile, this domain is proposed to have nucleotidylation activity. We used recombinant non-structural protein 9 of the arterivirus equine arteritis virus (EAV) and different biochemical assays, including irreversible labeling with a GTP analog followed by a proteomics analysis, to demonstrate the manganese-dependent covalent binding of guanosine and uridine phosphates to a lysine/histidine residue. Most likely this was the invariant lysine of the newly identified domain, named nidovirus RdRp-associated nucleotidyltransferase (NiRAN), whose substitution with alanine severely diminished the described binding. Furthermore, this mutation crippled EAV and prevented the replication of severe acute respiratory syndrome coronavirus (SARS-CoV) in cell culture, indicating that NiRAN is essential for nidoviruses. Potential functions supported by NiRAN may include nucleic acid ligation, mRNA capping and protein-primed RNA synthesis, possibilities that remain to be explored in future studies.",2015 Sep 30,"['Lehmann, Kathleen C.', 'Gulyaeva, Anastasia', 'Zevenhoven-Dobbe, Jessika C.', 'Janssen, George\xa0M.\xa0C.', 'Ruben, Mark', 'Overkleeft, Hermen S.', 'van\xa0Veelen, Peter A.', 'Samborskiy, Dmitry\xa0V.', 'Kravchenko, Alexander A.', 'Leontovich, Andrey M.', 'Sidorov, Igor A.', 'Snijder, Eric J.', 'Posthuma, Clara C.', 'Gorbalenya, Alexander E.']",Nucleic Acids Res,,,False
3f704d2ac81e0dc4e9e74ffd7d25f790baa6ebe1,PMC,"Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies",http://dx.doi.org/10.1128/mBio.02154-15,PMC4791852,26908579,CC BY-NC-SA,"The filovirus surface glycoprotein (GP) mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS) that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP(1) subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics.",2016 Feb 23,"['Bornholdt, Zachary A.', 'Ndungo, Esther', 'Fusco, Marnie L.', 'Bale, Shridhar', 'Flyak, Andrew I.', 'Crowe, James E.', 'Chandran, Kartik', 'Saphire, Erica Ollmann']",mBio,,,True
ab8c986073aea696e6a6f5bf6cb50738867cb27f,PMC,"Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies",http://dx.doi.org/10.1128/mBio.02154-15,PMC4791852,26908579,CC BY-NC-SA,"The filovirus surface glycoprotein (GP) mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS) that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP(1) subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics.",2016 Feb 23,"['Bornholdt, Zachary A.', 'Ndungo, Esther', 'Fusco, Marnie L.', 'Bale, Shridhar', 'Flyak, Andrew I.', 'Crowe, James E.', 'Chandran, Kartik', 'Saphire, Erica Ollmann']",mBio,,,False
54849b89718f1bda0b45defe9bbf3551dc220e42,PMC,"Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies",http://dx.doi.org/10.1128/mBio.02154-15,PMC4791852,26908579,CC BY-NC-SA,"The filovirus surface glycoprotein (GP) mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS) that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP(1) subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics.",2016 Feb 23,"['Bornholdt, Zachary A.', 'Ndungo, Esther', 'Fusco, Marnie L.', 'Bale, Shridhar', 'Flyak, Andrew I.', 'Crowe, James E.', 'Chandran, Kartik', 'Saphire, Erica Ollmann']",mBio,,,False
026c1adca90465f37753535891ca6dfe149ad0be,PMC,"Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies",http://dx.doi.org/10.1128/mBio.02154-15,PMC4791852,26908579,CC BY-NC-SA,"The filovirus surface glycoprotein (GP) mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS) that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP(1) subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics.",2016 Feb 23,"['Bornholdt, Zachary A.', 'Ndungo, Esther', 'Fusco, Marnie L.', 'Bale, Shridhar', 'Flyak, Andrew I.', 'Crowe, James E.', 'Chandran, Kartik', 'Saphire, Erica Ollmann']",mBio,,,False
8c1d8447fe266d96b7fb63fd8f836ef966bb6479,PMC,"Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies",http://dx.doi.org/10.1128/mBio.02154-15,PMC4791852,26908579,CC BY-NC-SA,"The filovirus surface glycoprotein (GP) mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS) that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP(1) subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics.",2016 Feb 23,"['Bornholdt, Zachary A.', 'Ndungo, Esther', 'Fusco, Marnie L.', 'Bale, Shridhar', 'Flyak, Andrew I.', 'Crowe, James E.', 'Chandran, Kartik', 'Saphire, Erica Ollmann']",mBio,,,False
e4f3286ca688e25cd8917943c36686416005afbe,PMC,Efficacy and Safety of Bortezomib in Multiple Myeloma Patients with Hepatitis B: A Multicenter Retrospective Study,http://dx.doi.org/10.4103/0366-6999.174508,PMC4799569,26831227,CC BY-NC-SA,"BACKGROUND: The efficacy and safety evidence of bortezomib in multiple myeloma (MM) patients with hepatitis B is vacant. This study aimed to investigate the efficacy and safety of bortezomib in MM patients with hepatitis B in China. METHODS: From 2006 to 2011, 739 newly diagnosed MM patients were screened for serum hepatitis B virus (HBV) biomarkers. HBV-infected patients were followed for HBV reactivation by monitoring of serum alanine transaminase (ALT) and HBV DNA load. The pattern of HBV reactivation in relation to bortezomib was evaluated. Seven hundred thirty-nine MM patients were included in this study. RESULTS: The prevalence of MM patients infected with HBV was 3.4% (n = 25), of which 17 cases were treated with bortezomib. Bortezomib had no significant influence on liver function (ALT before and after treatment: 36.69 ± 8.90 U/L vs. 11.31 ± 2.74 U/L, P = 0.19) and HBV DNA of MM patients with HBV (detectable HBV DNA percentage: 5.9% vs. 11.8%, P = 0.12). CONCLUSIONS: Bortezomib can be used safely and effectively in MM patients with hepatitis B. HBV prophylaxis and surveillance are recommended during the MM treatment.",2016 Feb 5,"['Lu, Jin', 'Chen, Wen-Ming', 'Geng, Chuan-Ying', 'Durie, Brian GM', 'Huang, Xiao-Jun']",Chin Med J (Engl),,,True
036a7af6f90c822210bcac1869a5e85303bb0ef6,PMC,"Analysis of the sex ratio of reported gonorrhoea incidence in Shenzhen, China",http://dx.doi.org/10.1136/bmjopen-2015-009629,PMC4800114,26975933,CC BY-NC,"OBJECTIVE: To assess the clinical process of gonorrhoea diagnosis and report in China, and to determine the difference of sex ratio between reported incidence based on reporting data and true diagnosis rate based on reference tests of gonorrhoea. SETTING: A total of 26 dermatology and sexually transmitted disease (STD) departments, 34 obstetrics-gynaecology clinics and 28 urology outpatient clinics selected from 34 hospitals of Shenzhen regarded as our study sites. PARTICIPANTS: A total of 2754 participants were recruited in this study, and 2534 participants completed the questionnaire survey and provided genital tract secretion specimens. There were 1106 male and 1428 female participants. Eligible participants were patients who presented for outpatient STD care at the selected clinics for the first time in October 2012 were at least 18 years old, and were able to give informed consent. OUTCOME MEASURES: Untested rate, true-positive rate, false-negative rate and unreported rate of gonorrhoea, as well as reported gonorrhoea incidence sex ratio and true diagnosis sex ratio were calculated and used to describe the results. RESULTS: 2534 participants were enrolled in the study. The untested rate of gonorrhoea among females was significantly higher than that among males (female 88.1%, male 68.3%, p=0.001). The male-to-female sex ratios of untested rate, true-positive rate, false-negative rate and unreported rate were 1:1.3, 1.2:1, 1:1.6 and 1:1.4, respectively. The reported gonorrhoea incidence sex ratio of new diagnosed gonorrhoea was 19.8:1 (male vs female: 87/1106 vs 5/1420), while the true diagnosis sex ratio was 2.5:1 (male vs female: 161/1106 vs 84/1420). These data indicate that the sex ratio of reported gonorrhoea incidence has been overestimated by a factor of 7.9 (19.8/2.5). CONCLUSIONS: We found the current reported gonorrhoea incidence and sex ratios to be inaccurate due to underestimations of gonorrhoea incidence, especially among women.",2016 Mar 14,"['Xiong, Mingzhou', 'Lan, Lina', 'Feng, Tiejian', 'Zhao, Guanglu', 'Wang, Feng', 'Hong, Fuchang', 'Wu, Xiaobing', 'Zhang, Chunlai', 'Wen, Lizhang', 'Liu, Aizhong', 'Best, John McCulloch', 'Tang, Weiming']",BMJ Open,,,True
1ee27c1e260d85de463d5db8aa8ab886e1df6180,PMC,Correlation Between UpToDate Searches and Reported Cases of Middle East Respiratory Syndrome During Outbreaks in Saudi Arabia,http://dx.doi.org/10.1093/ofid/ofw043,PMC4803184,27011953,CC BY-NC-ND,"Background. UpToDate is an online clinical decision support resource that is used extensively by clinicians around the world. Digital surveillance techniques have shown promise to aid with the detection and monitoring of infectious disease outbreaks. We sought to determine whether UpToDate searches for Middle East respiratory syndrome (MERS) could be used to detect and monitor MERS outbreaks in Saudi Arabia. Methods. We analyzed daily searches related to MERS in Jeddah and Riyadh, Saudi Arabia during 3 outbreaks in these cities in 2014 and 2015 and compared them with reported cases during the same periods. We also compared UpToDate MERS searches in the affected cities to those in a composite of 4 negative control cities for the 2 outbreaks in 2014. Results. UpToDate MERS searches during all 3 MERS outbreaks in Saudi Arabia showed a correlation to reported cases. In addition, UpToDate MERS search volume in Jeddah and Riyadh during the outbreak periods in 2014 was significantly higher than the concurrent search volume in the 4 negative control cities. In contrast, during the baseline periods, there was no difference between UpToDate searches for MERS in the affected cities compared with the negative control cities. Conclusions. UpToDate search activity seems to be useful for detecting and monitoring outbreaks of MERS in Saudi Arabia.",2016 Feb 18,"['Thorner, Anna R.', 'Cao, Bin', 'Jiang, Terrence', 'Warner, Amy J.', 'Bonis, Peter A.']",Open Forum Infect Dis,,,True
a03293a6ac86dd01a32f04eeea0f233f367fa742,PMC,The untapped cell biology of neglected tropical diseases,http://dx.doi.org/10.1091/mbc.E15-11-0771,PMC4803300,26915691,CC BY-NC-SA,"The World Health Organization lists a constellation of 17 tropical diseases that afflict approximately one in six individuals on the planet and, until recently, few resources have been devoted to the treatment and eradication of those diseases. They are often referred to as the diseases of the “bottom billion,” because they are most prevalent among the poorest individuals in impoverished tropical nations. However, the few studies that have been performed reveal an extraordinary world of molecular and cellular adaptations that facilitate the pathogens’ survival in hosts ranging from insects to humans. A compelling case can be made that even a modest investment toward understanding the basic molecular and cell biology of these neglected pathogens has a high probability of yielding exciting new cellular mechanisms and insights into novel ways of combating these diseases.",2016 Mar 1,"Sullivan, William",Mol Biol Cell,,,True
116c94dd67777e0c9806ef56974157060f5cca4b,PMC,A Case Report of a Middle East Respiratory Syndrome Survivor with Kidney Biopsy Results,http://dx.doi.org/10.3346/jkms.2016.31.4.635,PMC4810350,27051251,CC BY-NC,"A 68-year old man diagnosed with Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) presented with multiple pneumonic infiltrations on his chest X-ray, and the patient was placed on a mechanical ventilator because of progressive respiratory failure. Urinary protein excretion steadily increased for a microalbumin to creatinine ratio of 538.4 mg/g Cr and a protein to creatinine ratio of 3,025.8 mg/g Cr. The isotope dilution mass spectrometry traceable serum creatinine level increased to 3.0 mg/dL. We performed a kidney biopsy 8 weeks after the onset of symptoms. Acute tubular necrosis was the main finding, and proteinaceous cast formation and acute tubulointerstitial nephritis were found. There were no electron dense deposits observed with electron microscopy. We could not verify the virus itself by in situ hybridization and confocal microscopy (MERS-CoV co-stained with dipeptidyl peptidase 4). The viremic status, urinary virus excretion, and timely kidney biopsy results should be investigated with thorough precautions to reveal the direct effects of MERS-CoV with respect to renal complications.",2016 Apr 10,"['Cha, Ran-hui', 'Yang, Seung Hee', 'Moon, Kyung Chul', 'Joh, Joon-Sung', 'Lee, Ji Yeon', 'Shin, Hyoung-Shik', 'Kim, Dong Ki', 'Kim, Yon Su']",J Korean Med Sci,,,True
61ad64021b0e34d5e3a82a4310cc92d123a7061c,PMC,Spread of Mutant Middle East Respiratory Syndrome Coronavirus with Reduced Affinity to Human CD26 during the South Korean Outbreak,http://dx.doi.org/10.1128/mBio.00019-16,PMC4810480,26933050,CC BY-NC-SA,"The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (~35%). MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to July 2015, a large outbreak initiated by an infected traveler from the Arabian peninsula swept South Korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4%). Here, we show the rapid emergence and spread of a mutant MERS-CoV with reduced affinity to the human CD26 receptor during the South Korean outbreak. We isolated 13 new viral genomes from 14 infected patients treated at a hospital and found that 12 of these genomes possess a point mutation in the receptor-binding domain (RBD) of viral spike (S) protein. Specifically, 11 of these genomes have an I529T mutation in RBD, and 1 has a D510G mutation. Strikingly, both mutations result in reduced affinity of RBD to human CD26 compared to wild-type RBD, as measured by surface plasmon resonance analysis and cellular binding assay. Additionally, pseudotyped virus bearing an I529T mutation in S protein showed reduced entry into host cells compared to virus with wild-type S protein. These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26.",2016 Mar 1,"['Kim, Yuri', 'Cheon, Shinhye', 'Min, Chan-Ki', 'Sohn, Kyung Mok', 'Kang, Ying Jin', 'Cha, Young-Je', 'Kang, Ju-Il', 'Han, Seong Kyu', 'Ha, Na-Young', 'Kim, Gwanghun', 'Aigerim, Abdimadiyeva', 'Shin, Hyun Mu', 'Choi, Myung-Sik', 'Kim, Sanguk', 'Cho, Hyun-Soo', 'Kim, Yeon-Sook', 'Cho, Nam-Hyuk']",mBio,,,True
1ed5058204d1330e780f20fca2694bc0fd20d329,PMC,Drinking Water Quality and the Geospatial Distribution of Notified Gastro-Intestinal Infections,http://dx.doi.org/10.1515/sjph-2015-0028,PMC4820156,27646727,CC BY-NC-ND,"INTRODUCTION: Even brief episodes of fecal contamination of drinking water can lead directly to illness in the consumers. In water-borne outbreaks, the connection between poor microbial water quality and disease can be quickly identified. The impact of non-compliant drinking water samples due to E. coli taken for regular monitoring on the incidence of notified acute gastrointestinal infections has not yet been studied. METHODS: The objective of this study was to analyse the geographical distribution of notified acute gastrointestinal infections (AGI) in Slovenia in 2010, with hotspot identification. The second aim of the study was to correlate the fecal contamination of water supply system on the settlement level with the distribution of notified AGI cases. Spatial analysis using geo-information technology and other methods were used. RESULTS: Hot spots with the highest proportion of notified AGI cases were mainly identified in areas with small supply zones. The risk for getting AGI was drinking water contaminated with E. coli from supply zones with 50–1000 users: RR was 1.25 and significantly greater than one (p-value less than 0.001). CONCLUSION: This study showed the correlation between the frequency of notified AGI cases and non-compliant results in drinking water monitoring.",2015 Jun 9,"['GRILC, Eva', 'GALE, Ivanka', 'VERŠIČ, Aleš', 'ŽAGAR, Tina', 'SOČAN, Maja']",Zdr Varst,,,True
545cc28cf80d7f18232d1eafdcd3a7e9680a4b9f,PMC,Specific interference shRNA-expressing plasmids inhibit Hantaan virus infection in vitro and in vivo,http://dx.doi.org/10.1038/aps.2015.165,PMC4820803,26972493,CC BY-NC-ND,"AIM: To investigate the antiviral effects of vectors expressing specific short hairpin RNAs (shRNAs) against Hantaan virus (HTNV) infection in vitro and in vivo. METHODS: Based on the effects of 4 shRNAs targeting different regions of HTNV genomic RNA on viral replication, the most effective RNA interference fragments of the S and M genes were constructed in pSilencer-3.0-H1 vectors, and designated pSilencer-S and pSilencer-M, respectively. The antiviral effect of pSilencer-S/M against HTNV was evaluated in both HTNV-infected Vero-E6 cells and mice. RESULTS: In HTNV-infected Vero-E6 cells, pSilencer-S and pSilencer-M targeted the viral nucleocapsid proteins and envelope glycoproteins, respectively, as revealed in the immunofluorescence assay. Transfection with pSilencer-S or pSilencer-M (1, 2, 4 μg) markedly inhibited the viral antigen expression in dose- and time-dependent manners. Transfection with either plasmid (2 μg) significantly decreased HTNV-RNA level at 3 day postinfectin (dpi) and the progeny virus titer at 5 dpi. In mice infected with lethal doses of HTNV, intraperitoneal injection of pSilencer-S or pSilencer-M (30 μg) considerably increased the survival rates and mean time to death, and significantly reduced the mean virus yields and viral RNA level, and alleviated virus-induced pathological lesions in lungs, brains and kidneys. CONCLUSION: Plasmid-based shRNAs potently inhibit HTNV replication in vitro and in vivo. Our results provide a basis for development of shRNA as therapeutics for HTNV infections in humans.",2016 Apr 14,"['Liu, Yuan-yuan', 'Chen, Liang-jun', 'Zhong, Yan', 'Shen, Meng-xin', 'Ma, Nian', 'Liu, Bing-yu', 'Luo, Fan', 'Hou, Wei', 'Yang, Zhan-qiu', 'Xiong, Hai-rong']",Acta Pharmacol Sin,,,True
fbcdafa6bac2c69c1f5afafc5338f777f234d592,PMC,Reverse vaccinology 2.0: Human immunology instructs vaccine antigen design,http://dx.doi.org/10.1084/jem.20151960,PMC4821650,27022144,CC BY-NC-SA,"Traditionally, vaccines have been developed by cultivating infectious agents and isolating the inactivated whole pathogen or some of its purified components. 20 years ago, reverse vaccinology enabled vaccine discovery and design based on information deriving from the sequence of microbial genomes rather than via the growth of pathogens. Today, the high throughput discovery of protective human antibodies, sequencing of the B cell repertoire, and the increasing structural characterization of protective antigens and epitopes provide the molecular and mechanistic understanding to drive the discovery of novel vaccines that were previously impossible. We are entering a “reverse vaccinology 2.0” era.",2016 Apr 4,"['Rappuoli, Rino', 'Bottomley, Matthew J.', 'D’Oro, Ugo', 'Finco, Oretta', 'De Gregorio, Ennio']",J Exp Med,,,True
f7ef8b5d989ac724f2520aa8a0a83e60f8851e91,PMC,"Chemo-enzymatic synthesis of site-specific isotopically labeled nucleotides for use in NMR resonance assignment, dynamics and structural characterizations",http://dx.doi.org/10.1093/nar/gkv1333,PMC4824079,26657632,CC BY-NC,"Stable isotope labeling is central to NMR studies of nucleic acids. Development of methods that incorporate labels at specific atomic positions within each nucleotide promises to expand the size range of RNAs that can be studied by NMR. Using recombinantly expressed enzymes and chemically synthesized ribose and nucleobase, we have developed an inexpensive, rapid chemo-enzymatic method to label ATP and GTP site specifically and in high yields of up to 90%. We incorporated these nucleotides into RNAs with sizes ranging from 27 to 59 nucleotides using in vitro transcription: A-Site (27 nt), the iron responsive elements (29 nt), a fluoride riboswitch from Bacillus anthracis (48 nt), and a frame-shifting element from a human corona virus (59 nt). Finally, we showcase the improvement in spectral quality arising from reduced crowding and narrowed linewidths, and accurate analysis of NMR relaxation dispersion (CPMG) and TROSY-based CEST experiments to measure μs-ms time scale motions, and an improved NOESY strategy for resonance assignment. Applications of this selective labeling technology promises to reduce difficulties associated with chemical shift overlap and rapid signal decay that have made it challenging to study the structure and dynamics of large RNAs beyond the 50 nt median size found in the PDB.",2016 Apr 7,"['Longhini, Andrew P.', 'LeBlanc, Regan M.', 'Becette, Owen', 'Salguero, Carolina', 'Wunderlich, Christoph H.', 'Johnson, Bruce A.', ""D'Souza, Victoria M."", 'Kreutz, Christoph', 'Dayie, T. Kwaku']",Nucleic Acids Res,,,True
d1d5731887f0cd5d6aa82905be71655febb4d8b5,PMC,The standard of care of patients with ARDS: ventilatory settings and rescue therapies for refractory hypoxemia,http://dx.doi.org/10.1007/s00134-016-4325-4,PMC4828494,27040102,CC BY-NC,"PURPOSE: Severe ARDS is often associated with refractory hypoxemia, and early identification and treatment of hypoxemia is mandatory. For the management of severe ARDS ventilator settings, positioning therapy, infection control, and supportive measures are essential to improve survival. METHODS AND RESULTS: A precise definition of life-threating hypoxemia is not identified. Typical clinical determinations are: arterial partial pressure of oxygen < 60 mmHg and/or arterial oxygenation < 88 % and/or the ratio of PaO(2)/FIO(2) < 100. For mechanical ventilation specific settings are recommended: limitation of tidal volume (6 ml/kg predicted body weight), adequate high PEEP (>12 cmH(2)O), a recruitment manoeuvre in special situations, and a ‘balanced’ respiratory rate (20-30/min). Individual bedside methods to guide PEEP/recruitment (e.g., transpulmonary pressure) are not (yet) available. Prone positioning [early (≤ 48 hrs after onset of severe ARDS) and prolonged (repetition of 16-hr-sessions)] improves survival. An advanced infection management/control includes early diagnosis of bacterial, atypical, viral and fungal specimen (blood culture, bronchoalveolar lavage), and of infection sources by CT scan, followed by administration of broad-spectrum anti-infectives. Neuromuscular blockage (Cisatracurium ≤ 48 hrs after onset of ARDS), as well as an adequate sedation strategy (score guided) is an important supportive therapy. A negative fluid balance is associated with improved lung function and the use of hemofiltration might be indicated for specific indications. CONCLUSIONS: A specific standard of care is required for the management of severe ARDS with refractory hypoxemia.",2016 Apr 4,"['Bein, Thomas', 'Grasso, Salvatore', 'Moerer, Onnen', 'Quintel, Michael', 'Guerin, Claude', 'Deja, Maria', 'Brondani, Anita', 'Mehta, Sangeeta']",Intensive Care Med,,,True
6107c0ccde81ea8fb7c6a10fc39048eedf5c2447,PMC,The elusive quest for RNA knots,http://dx.doi.org/10.1080/15476286.2015.1132069,PMC4829277,26828280,CC BY-NC,"Physical entanglement, and particularly knots arise spontaneously in equilibrated polymers that are sufficiently long and densely packed. Biopolymers are no exceptions: knots have long been known to occur in proteins as well as in encapsidated viral DNA. The rapidly growing number of RNA structures has recently made it possible to investigate the incidence of physical knots in this type of biomolecule, too. Strikingly, no knots have been found to date in the known RNA structures. In this Point of View Article we discuss the absence of knots in currently available RNAs and consider the reasons why knots in RNA have not yet been found, despite the expectation that they should exist in Nature. We conclude by singling out a number of RNA sequences that, based on the properties of their predicted secondary structures, are good candidates for knotted RNAs.",2016 Feb 1,"['Burton, Aaron S.', 'Di Stefano, Marco', 'Lehman, Niles', 'Orland, Henri', 'Micheletti, Cristian']",RNA Biol,,,True
3e107cc95d4428962d4fc859f24b87bf0b8433e5,PMC,A Comment on “Quaternary Prevention in Public Health” by Dr. Jong-Myon Bae,http://dx.doi.org/10.3961/jpmph.16.031,PMC4829367,27055551,CC BY-NC,,2016 Mar 31,"Jamoulle, Marc",J Prev Med Public Health,,,True
437023e7796433e7123e918659e67f460ad876f7,PMC,The Author Reply: A Comment on “Quaternary Prevention in Public Health”,http://dx.doi.org/10.3961/jpmph.16.032,PMC4829374,27055552,CC BY-NC,,2016 Mar 31,"Bae, Jong-Myon",J Prev Med Public Health,,,False
657558034931a24e09f761877fed36cb70f4f6fe,PMC,Epidemiology and vaccine of porcine epidemic diarrhea virus in China: a mini-review,http://dx.doi.org/10.1292/jvms.15-0446,PMC4829501,26537549,CC BY-NC-ND,"Porcine epidemic diarrhea (PED) is an intestinal infectious disease caused by porcine epidemic diarrhea virus (PEDV); manifestations of the disease are diarrhea, vomiting and dehydration. Starting from the end of 2010, a PED outbreak occurred in several pig-producing provinces in southern China. Subsequently, the disease spread throughout the country and caused enormous economic losses to the pork industry. Accumulating studies demonstrated that new PEDV variants that appeared in China were responsible for the PED outbreak. In the current mini-review, we summarize PEDV epidemiology and vaccination in China.",2016 Mar 3,"['SUN, Dongbo', 'WANG, Xinyu', 'WEI, Shan', 'CHEN, Jianfei', 'FENG, Li']",J Vet Med Sci,,,True
e7b8761e03a3ce7edd5c0df23946c4ac8618c708,PMC,Development of a novel detection system for microbes from bovine diarrhea by real-time PCR,http://dx.doi.org/10.1292/jvms.15-0552,PMC4829504,26616156,CC BY-NC-ND,"Diarrhea in cattle is one of the most economically costly disorders, decreasing milk production and weight gain. In the present study, we established a novel simultaneous detection system using TaqMan real-time PCR designed as a system for detection of microbes from bovine diarrhea using real-time PCR (referred to as Dembo-PCR). Dembo-PCR simultaneously detects a total of 19 diarrhea-causing pathogens, including viruses, bacteria and protozoa. Specific primer–probe sets were newly designed for 7 pathogens and were synthesized on the basis of previous reports for 12 pathogens. Assays were optimized to react under the same reaction conditions. The PCR efficiency and correlation coefficient (R(2)) of standard curves for each assay were more than 80% and 0.9766, respectively. Furthermore, the sensitivity of Dembo-PCR in fecal sample analysis was measured with feces spiked with target pathogens or synthesized DNA that included specific nucleotide target regions. The resulting limits of detection (LOD) for virus-spiked samples, bacteria and DNA fragments were 0.16–1.6 TCID(50) (PFU/reaction), 1.3–13 CFU/reaction and 10–100 copies/reaction, respectively. All reactions showed high sensitivity in pathogen detection. A total of 8 fecal samples, collected from 6 diarrheic cattle, 1 diarrheic calf and 1 healthy cow, were tested using Dembo-PCR to validate the assay’s clinical performance. The results revealed that bovine coronavirus had infected all diarrheic adult cattle and that bovine torovirus had infected the diarrheic calf. These results suggest that Dembo-PCR may be a powerful tool for diagnosing infectious agents in cattle diarrhea.",2016 Mar 30,"['TSUCHIAKA, Shinobu', 'MASUDA, Tsuneyuki', 'SUGIMURA, Satoshi', 'KOBAYASHI, Suguru', 'KOMATSU, Natsumi', 'NAGAI, Makoto', 'OMATSU, Tsutomu', 'FURUYA, Tetsuya', 'OBA, Mami', 'KATAYAMA, Yukie', 'KANDA, Shuhei', 'YOKOYAMA, Tadashi', 'MIZUTANI, Tetsuya']",J Vet Med Sci,,,True
251b7d1d3aa75088629d05bfab8ea46b6356b791,PMC,Development of a novel detection system for microbes from bovine diarrhea by real-time PCR,http://dx.doi.org/10.1292/jvms.15-0552,PMC4829504,26616156,CC BY-NC-ND,"Diarrhea in cattle is one of the most economically costly disorders, decreasing milk production and weight gain. In the present study, we established a novel simultaneous detection system using TaqMan real-time PCR designed as a system for detection of microbes from bovine diarrhea using real-time PCR (referred to as Dembo-PCR). Dembo-PCR simultaneously detects a total of 19 diarrhea-causing pathogens, including viruses, bacteria and protozoa. Specific primer–probe sets were newly designed for 7 pathogens and were synthesized on the basis of previous reports for 12 pathogens. Assays were optimized to react under the same reaction conditions. The PCR efficiency and correlation coefficient (R(2)) of standard curves for each assay were more than 80% and 0.9766, respectively. Furthermore, the sensitivity of Dembo-PCR in fecal sample analysis was measured with feces spiked with target pathogens or synthesized DNA that included specific nucleotide target regions. The resulting limits of detection (LOD) for virus-spiked samples, bacteria and DNA fragments were 0.16–1.6 TCID(50) (PFU/reaction), 1.3–13 CFU/reaction and 10–100 copies/reaction, respectively. All reactions showed high sensitivity in pathogen detection. A total of 8 fecal samples, collected from 6 diarrheic cattle, 1 diarrheic calf and 1 healthy cow, were tested using Dembo-PCR to validate the assay’s clinical performance. The results revealed that bovine coronavirus had infected all diarrheic adult cattle and that bovine torovirus had infected the diarrheic calf. These results suggest that Dembo-PCR may be a powerful tool for diagnosing infectious agents in cattle diarrhea.",2016 Mar 30,"['TSUCHIAKA, Shinobu', 'MASUDA, Tsuneyuki', 'SUGIMURA, Satoshi', 'KOBAYASHI, Suguru', 'KOMATSU, Natsumi', 'NAGAI, Makoto', 'OMATSU, Tsutomu', 'FURUYA, Tetsuya', 'OBA, Mami', 'KATAYAMA, Yukie', 'KANDA, Shuhei', 'YOKOYAMA, Tadashi', 'MIZUTANI, Tetsuya']",J Vet Med Sci,,,False
f266600e61a8c0fbceb48929b7250a9f16771c9f,PMC,Chinese People's Liberation Army on Action of Fighting against Ebola in Africa: Implications and Challenges,http://dx.doi.org/10.4103/0366-6999.156822,PMC4830329,25963370,CC BY-NC-SA,,2015 May 20,"['Li, Ying', 'Tang, Sheng-Lan', 'Sato, Kaori', 'Cao, Jia']",Chin Med J (Engl),,,True
3c4f6a15937affaf17af8ba34d069cc71968db53,PMC,"Design, Synthesis, and Antiviral Activity of Novel Ribonucleosides of 1,2,3‐Triazolylbenzyl‐aminophosphonates",http://dx.doi.org/10.1002/ardp.201500292,PMC4832832,26575425,CC BY-NC-ND,"A novel series of ribonucleosides of 1,2,3‐triazolylbenzyl‐aminophosphonates was synthesized through the Kabachnik–Fields reaction using I(2) as catalyst followed by copper‐catalyzed cycloaddition of the azide–alkyne reaction (CuAAC). All structures of the newly prepared compounds were characterized by (1)H NMR, (13)C NMR, and HRMS spectra. The structures of 2e, 2f, 3d, and 3g were further confirmed by X‐ray diffraction analysis. These compounds were tested against various strains of DNA and RNA viruses; compounds 4b and 4c showed a modest inhibitory activity against respiratory syncytial virus (RSV) and compound 4h displayed modest inhibitory activity against Coxsackie virus B4.",2016 Jan 17,"['Ouahrouch, Abdelaaziz', 'Taourirte, Moha', 'Schols, Dominique', 'Snoeck, Robert', 'Andrei, Graciela', 'Engels, Joachim W.', 'Lazrek, Hassan B.']",Arch Pharm (Weinheim),,,True
3225941fdfbe72b9784e329bcd83daeb8d993be0,PMC,"Design, Synthesis, and Antiviral Activity of Novel Ribonucleosides of 1,2,3‐Triazolylbenzyl‐aminophosphonates",http://dx.doi.org/10.1002/ardp.201500292,PMC4832832,26575425,CC BY-NC-ND,"A novel series of ribonucleosides of 1,2,3‐triazolylbenzyl‐aminophosphonates was synthesized through the Kabachnik–Fields reaction using I(2) as catalyst followed by copper‐catalyzed cycloaddition of the azide–alkyne reaction (CuAAC). All structures of the newly prepared compounds were characterized by (1)H NMR, (13)C NMR, and HRMS spectra. The structures of 2e, 2f, 3d, and 3g were further confirmed by X‐ray diffraction analysis. These compounds were tested against various strains of DNA and RNA viruses; compounds 4b and 4c showed a modest inhibitory activity against respiratory syncytial virus (RSV) and compound 4h displayed modest inhibitory activity against Coxsackie virus B4.",2016 Jan 17,"['Ouahrouch, Abdelaaziz', 'Taourirte, Moha', 'Schols, Dominique', 'Snoeck, Robert', 'Andrei, Graciela', 'Engels, Joachim W.', 'Lazrek, Hassan B.']",Arch Pharm (Weinheim),,,False
d24afd9ee025b53015824be203db539009964fbd,PMC,Thin-section Computed Tomography Detects Long-term Pulmonary Sequelae 3 Years after Novel Influenza A Virus-associated Pneumonia,http://dx.doi.org/10.4103/0366-6999.154285,PMC4834006,25836610,CC BY-NC-SA,"BACKGROUND: The aim of this research was to evaluate long-term pulmonary sequelae on paired inspiration-expiration thin-section computed tomography (CT) scans 3 years after influenza A (H1N1) virus-associated pneumonia, and to analyze the affecting factors on pulmonary fibrosis. METHODS: Twenty-four patients hospitalized with H1N1 virus-associated pneumonia at our hospital between September 2009 and January 2010 were included. The patients underwent thin-section CT 3 years after recovery. Abnormal pulmonary lesion patterns (ground-glass opacity, consolidation, parenchymal bands, air trapping, and reticulation) and evidence of fibrosis (architectural distortion, traction bronchiectasis, or honeycombing) were evaluated on follow-up thin-section CT. Patients were assigned to Group 1 (with CT evidence of fibrosis) and Group 2 (without CT evidence of fibrosis). Demographics, rate of mechanical ventilation therapy, rate of intensive care unit admission, cumulative prednisolone-equivalent dose, laboratory tests results (maximum levels of alanine aminotransferase, aspartate transaminase [AST], lactate dehydrogenase [LDH], and creatine kinase [CK]), and peak radiographic opacification of 24 patients during the course of their illness in the hospital were compared between two groups. RESULTS: Parenchymal abnormality was present in 17 of 24 (70.8%) patients and fibrosis occurred in 10 of 24 (41.7%) patients. Patients in Group 1 (10/24; 41.7%) had a higher rate of mechanical ventilation therapy (Z = −2.340, P = 0.019), higher number of doses of cumulative prednisolone-equivalent (Z = −2.579, P = 0.010), higher maximum level of laboratory tests results (AST [Z = −2.140, P = 0.032], LDH [Z = −3.227, P = 0.001], and CK [Z = −3.345, P = 0.019]), and higher peak opacification on chest radiographs (Z = −2.743, P = 0.006) than patients in group 2 (14/24; 58.3%). CONCLUSIONS: H1N1 virus-associated pneumonia frequently is followed by long-term pulmonary sequelae, including fibrotic changes, in lung parenchyma. Patients who need more steroid therapy, need more mechanical ventilation therapy, had higher laboratory tests results (maximum levels of AST, LDH, and CK), and had higher peak opacification on chest radiographs during treatment are more likely to develop lung fibrosis.",2015 Apr 5,"['Xing, Zhi-Heng', 'Sun, Xin', 'Xu, Long', 'Wu, Qi', 'Li, Li', 'Wu, Xian-Jie', 'Shao, Xu-Guang', 'Zhao, Xin-Qian', 'Wang, Jing-Hua', 'Ma, Long-Yan', 'Wang, Kai']",Chin Med J (Engl),,,True
e46e1768a48965ba42073cc744b7278055859174,PMC,Acute Myopericarditis caused by Human Metapneumovirus,http://dx.doi.org/10.3947/ic.2016.48.1.36,PMC4835433,27104014,CC BY-NC,"Human metapneumovirus is known to be similar to respiratory syncytial virus. Because of an incomplete protective immune response to new genotypes, re-infection occurs frequently, especially in the elderly. However, the clinical manifestations of human metapneumovirus need to be further characterized in adults. A 73-year-old woman presented to the emergency room with acute dyspnea, chest discomfort and influenza-like illness. The patient was diagnosed with human metapneumovirus infection, complicated by pneumonia and myopericarditis. With supportive care including oxygen supplementation, the patient recovered completely without any serious sequelae. Human metapneumovirus infection may contribute to the development of cardiovascular manifestations, particularly in the elderly population.",2016 Mar 31,"['Choi, Min Joo', 'Song, Joon Young', 'Yang, Tae Un', 'Jeon, Ji Ho', 'Noh, Ji Yun', 'Hong, Kyung Wook', 'Cheong, Hee Jin', 'Kim, Woo Joo']",Infect Chemother,,,True
c5c0550f37aa2212ccdc4608e7117c142965e119,PMC,Guidelines for the Laboratory Diagnosis of Middle East Respiratory Syndrome Coronavirus in Korea,http://dx.doi.org/10.3947/ic.2016.48.1.61,PMC4835438,27104019,CC BY-NC,"The recent outbreak of Middle East respiratory syndrome (MERS) in Korea was unexpected that laboratory response had to be built up urgently during the outbreak. The outbreak was almost all healthcare-associated, which was aggravated by lack of availability in laboratory diagnosis of MERS-CoV on site. On behalf of the MERS joint public and private sector response committee (MERS Joint committee), the Korean Society for Laboratory Medicine (KSLM) launched a MERS response task force (MERS KSLM TF) to facilitate clinical laboratories set up MERS molecular diagnosis. MERS TF established guidelines for laboratory diagnosis of MERS-CoV and provided it to all participating laboratories as the official guidance of MERS Joint committee. This guideline was used for procedure manual of molecular diagnosis of MERS-CoV and laboratory safety manual.",2016 Mar 31,"['Lee, Hyukmin', 'Ki, Chang-Seok', 'Sung, Heungsup', 'Kim, Sinyoung', 'Seong, Moon-Woo', 'Yong, Dongeun', 'Kim, Jae-Seok', 'Lee, Mi-Kyung', 'Kim, Mi-Na', 'Choi, Jong-Rak', 'Kim, Jeong-Ho', None]",Infect Chemother,,,True
09cec865941962acf6060e72ef9c477c196c4c3b,PMC,Guidelines for the Laboratory Diagnosis of Middle East Respiratory Syndrome Coronavirus in Korea,http://dx.doi.org/10.3947/ic.2016.48.1.61,PMC4835438,27104019,CC BY-NC,"The recent outbreak of Middle East respiratory syndrome (MERS) in Korea was unexpected that laboratory response had to be built up urgently during the outbreak. The outbreak was almost all healthcare-associated, which was aggravated by lack of availability in laboratory diagnosis of MERS-CoV on site. On behalf of the MERS joint public and private sector response committee (MERS Joint committee), the Korean Society for Laboratory Medicine (KSLM) launched a MERS response task force (MERS KSLM TF) to facilitate clinical laboratories set up MERS molecular diagnosis. MERS TF established guidelines for laboratory diagnosis of MERS-CoV and provided it to all participating laboratories as the official guidance of MERS Joint committee. This guideline was used for procedure manual of molecular diagnosis of MERS-CoV and laboratory safety manual.",2016 Mar 31,"['Lee, Hyukmin', 'Ki, Chang-Seok', 'Sung, Heungsup', 'Kim, Sinyoung', 'Seong, Moon-Woo', 'Yong, Dongeun', 'Kim, Jae-Seok', 'Lee, Mi-Kyung', 'Kim, Mi-Na', 'Choi, Jong-Rak', 'Kim, Jeong-Ho', None]",Infect Chemother,,,True
6a7dabe4468f0c2cc573b03773865daf3ee1812f,PMC,Instructions for Authors,,PMC4837812,,CC BY-NC-SA,,2015 Jan 5,,Chin Med J (Engl),,,False
20a7363b3ad53472952cc80c03489ff56b7178bc,PMC,Safety of Tdap vaccine in pregnant women: an observational study,http://dx.doi.org/10.1136/bmjopen-2015-010911,PMC4838681,27091823,CC BY-NC,"OBJECTIVES: Actively recruit and intensively follow pregnant women receiving a dose of acellular pertussis vaccine for 4 weeks after vaccination. DESIGN AND SETTINGS: A prospective observational study conducted in 2 New Zealand regions. PARTICIPANTS: Women in their 28th–38th week of pregnancy, recruited from primary care and antenatal clinics at the time of Tdap administration. Telephone interviews were conducted at 48 h and 4 weeks postvaccination. MAIN OUTCOMES MEASURES: Outcomes were injection site reactions, systemic symptoms and serious adverse events (SAEs). Where available, data have been classified and reported according to Brighton Collaboration definitions. RESULTS: 793 women participated with 27.9% receiving trivalent inactivated influenza vaccine concomitantly. 79% of participants reported mild or moderate pain and 2.6% severe pain. Any swelling was reported by 7.6%, induration by 12.0% (collected from 1 site only, n=326), and erythema by 5.8% of participants. Fever was reported by 17 (2.1%) participants, 14 of these occurred within 24 h. Headache, dizziness, nausea, myalgia or arthralgia was reported by <4% of participants, respectively, and fatigue by 8.4%. During the study period, there were 115 adverse events in 113 participants, most of which were minor. At the end of the reporting period, 31 events were classified as serious (eg, obstetric bleeding, hypertension, infection, tachycardia, preterm labour, exacerbation of pre-existing condition and pre-eclampsia). All had variable onset time from vaccination. There were two perinatal deaths. Clinician assessment of all SAEs found none likely to be vaccine related. CONCLUSIONS: Vaccination with Tdap in pregnant women was well tolerated with no SAE likely to be caused by the vaccine. TRIAL REGISTRATION NUMBER: ACTRN12613001045707.",2016 Apr 18,"['Petousis-Harris, Helen', 'Walls, Tony', 'Watson, Donna', 'Paynter, Janine', 'Graham, Patricia', 'Turner, Nikki']",BMJ Open,,,True
aa56d0f7345de56d6faa6791733fac0863fb1137,PMC,Measurement of serum 7α-hydroxy-4-cholesten-3-one as a marker of bile acid malabsorption in dogs with chronic diarrhoea: a pilot study,http://dx.doi.org/10.1136/vetreco-2015-000163,PMC4838766,27110372,CC BY-NC,"Bile acid malabsorption is a common cause of chronic diarrhoea in people, however it has never previously been investigated in dogs, despite clinical suspicion of its existence. The goal of this study was to assess the feasibility of measuring serum 7α-hydroxy-4-cholesten-3-one (C4) in dogs, as a potential marker of bile acid malabsorption, and to see whether this is related to clinical disease severity or the presence of hypocobalaminaemia. Serum C4 concentration was measured in 20 clinically healthy control dogs and 17 dogs with chronic diarrhoea. Three of the 17 affected dogs (17.6 per cent) had a C4 concentration significantly above the range of clinically healthy dogs; these dogs were all poorly responsive to conventional therapy. These results suggest that bile acid malabsorption may be a clinically relevant disorder in dogs with chronic diarrhoea and serum C4 may be a useful tool to investigate this further.",2016 Apr 6,"['Kent, A. C. C.', 'Cross, G.', 'Taylor, D. R.', 'Sherwood, R. A.', 'Watson, P. J.']",Vet Rec Open,,,True
f4b5aafaa63b47a81bc8af2881fb6bbe7a5ff37c,PMC,Measurement of serum 7α-hydroxy-4-cholesten-3-one as a marker of bile acid malabsorption in dogs with chronic diarrhoea: a pilot study,http://dx.doi.org/10.1136/vetreco-2015-000163,PMC4838766,27110372,CC BY-NC,"Bile acid malabsorption is a common cause of chronic diarrhoea in people, however it has never previously been investigated in dogs, despite clinical suspicion of its existence. The goal of this study was to assess the feasibility of measuring serum 7α-hydroxy-4-cholesten-3-one (C4) in dogs, as a potential marker of bile acid malabsorption, and to see whether this is related to clinical disease severity or the presence of hypocobalaminaemia. Serum C4 concentration was measured in 20 clinically healthy control dogs and 17 dogs with chronic diarrhoea. Three of the 17 affected dogs (17.6 per cent) had a C4 concentration significantly above the range of clinically healthy dogs; these dogs were all poorly responsive to conventional therapy. These results suggest that bile acid malabsorption may be a clinically relevant disorder in dogs with chronic diarrhoea and serum C4 may be a useful tool to investigate this further.",2016 Apr 6,"['Kent, A. C. C.', 'Cross, G.', 'Taylor, D. R.', 'Sherwood, R. A.', 'Watson, P. J.']",Vet Rec Open,,,False
79697e89c89116547c539a46e2041bd81d52d5d0,PMC,"Relative frequency, Possible Risk Factors, Viral Codetection Rates, and Seasonality of Respiratory Syncytial Virus Among Children With Lower Respiratory Tract Infection in Northeastern Brazil",http://dx.doi.org/10.1097/MD.0000000000003090,PMC4839792,27082548,CC BY-NC-ND,"Few studies, each limited to a single major city, have investigated the prevalence and seasonal patterns of different viruses among children with low respiratory tract infections (LRTI) in Northeastern Brazil. The aim of this study was to determine the frequency of respiratory syncytial virus (RSV) and of 7 other viruses in children for LRTI in 4 capitals from this region, and investigate their association with several risk factors, including meteorological data. From April 2012 to March 2013, 507 children, aged up to 24 months and hospitalized with LRTI in one of the participating centers at Aracajú, Salvador, Recife, and Maceió, had a sample of nasopharyngeal aspirate collected and analyzed for the following viruses by reverse-transcription polymerase chain reaction followed by hybridization on low-density microarrays: RSV, influenza, parainfluenza, adenovirus, rhinovirus, metapneumovirus, bocavirus, and coronavirus. The result was positive in 66.5% of cases, RSV was the most common virus (40.2%). Except for rhinovirus (17%), all other virus had frequency rates lower than 6%. Viral coinfections were detected in 13.8% of samples. Possible related risk factors for RSV infection were low age upon entry, attendance of daycare, low gestational age, and low educational level of the father. The relative frequency of viral infections was associated with increasing temperature and decreasing humidity separately, but the results also suggested both associated with increased frequency of RSV. Some of these findings differ from those reported for other regions in Brazil and may be used to guide policies that address LRTI.",2016 Apr 18,"['Gurgel, Ricardo Queiroz', 'Bezerra, Patrícia Gomes de Matos', 'Duarte, Maria do Carmo Menezes Bezerra', 'Moura, Adriana Ávila', 'Souza, Edna Lucia', 'Silva, Luciana Sobral da Silveira', 'Suzuki, Claudia Eiko', 'Peixoto, Rodrigo Buzzatti']",Medicine (Baltimore),,,True
f9e2f23a7972e897b3ceff41187c444bfdb4ee7f,PMC,"Corrigendum to “Middle East Respiratory Syndrome Coronavirus Outbreak in the Republic of Korea, 2015” [Volume 6, Issue 4, August 2015, 269–278]",http://dx.doi.org/10.1016/j.phrp.2016.03.002,PMC4850385,27218017,CC BY-NC-ND,,2016 Apr 10,,Osong Public Health Res Perspect,,,False
22f98765239b02e3e5810fd976971ca87bab092b,PMC,A Comparison of the Cambodian and the South Korean Health Care System,http://dx.doi.org/10.6118/jmm.2016.22.1.1,PMC4854654,27152305,CC BY-NC,,2016 Apr 26,"['Hwang, Ji-Young', 'Seap, Bel', 'Kim, Tae-Hee']",J Menopausal Med,,,True
adf7da31a81303705ded170f6f60ba708834d024,PMC,Possible Transfusion-Related Acute Lung Injury Following Convalescent Plasma Transfusion in a Patient With Middle East Respiratory Syndrome,http://dx.doi.org/10.3343/alm.2016.36.4.393,PMC4855066,27139619,CC BY-NC,,2016 Jul 25,"['Chun, Sejong', 'Chung, Chi Ryang', 'Ha, Young Eun', 'Han, Tae Hee', 'Ki, Chang-Seok', 'Kang, Eun-Suk', 'Park, Jin Kyeong', 'Peck, Kyong Ran', 'Cho, Duck']",Ann Lab Med,,,True
2068afc018b995910ee71c91eec83c3d90b80f0e,PMC,"Qingfei Xiaoyan Wan, a traditional Chinese medicine formula, ameliorates Pseudomonas aeruginosa–induced acute lung inflammation by regulation of PI3K/AKT and Ras/MAPK pathways",http://dx.doi.org/10.1016/j.apsb.2016.03.002,PMC4856955,27175332,CC BY-NC-ND,"Gram-negative pathogen–induced nosocomial infections and resistance are a most serious menace to global public health. Qingfei Xiaoyan Wan (QF), a traditional Chinese medicine (TCM) formula, has been used clinically in China for the treatment of upper respiratory tract infections, acute or chronic bronchitis and pulmonary infection. In this study, the effects of QF on Pseudomonas aeruginosa–induced acute pneumonia in mice were evaluated. The mechanisms by which four typical anti-inflammatory ingredients from QF, arctigenin (ATG), cholic acid (CLA), chlorogenic acid (CGA) and sinapic acid (SPA), regulate anti-inflammatory signaling pathways and related targets were investigated using molecular biology and molecular docking techniques. The results showed that pretreatment with QF significantly inhibits the release of cytokines (TNF-α and IL-6) and chemokines (IL-8 and RANTES), reduces leukocytes recruitment into inflamed tissues and ameliorates pulmonary edema and necrosis. In addition, ATG was identified as the primary anti-inflammatory agent with action on the PI3K/AKT and Ras/MAPK pathways. CLA and CGA enhanced the actions of ATG and exhibited synergistic NF-κB inactivation effects possibly via the Ras/MAPK signaling pathway. Moreover, CLA is speculated to target FGFR and MEK firstly. Overall, QF regulated the PI3K/AKT and Ras/MAPK pathways to inhibit pathogenic bacterial infections effectively.",2016 May 22,"['Hou, Yuanyuan', 'Nie, Yan', 'Cheng, Binfeng', 'Tao, Jin', 'Ma, Xiaoyao', 'Jiang, Min', 'Gao, Jie', 'Bai, Gang']",Acta Pharm Sin B,,,False
ed52c50fb3ff01140790f21c6e9716a8cd3c9fa8,PMC,G-quadruplex-interacting compounds alter latent DNA replication and episomal persistence of KSHV,http://dx.doi.org/10.1093/nar/gkw038,PMC4856979,26837574,CC BY-NC,"Kaposi's sarcoma associated herpesvirus (KSHV) establishes life-long latent infection by persisting as an extra-chromosomal episome in the infected cells and by maintaining its genome in dividing cells. KSHV achieves this by tethering its epigenome to the host chromosome by latency associated nuclear antigen (LANA), which binds in the terminal repeat (TR) region of the viral genome. Sequence analysis of the TR, a GC-rich DNA element, identified several potential Quadruplex G-Rich Sequences (QGRS). Since quadruplexes have the tendency to obstruct DNA replication, we used G-quadruplex stabilizing compounds to examine their effect on latent DNA replication and the persistence of viral episomes. Our results showed that these G-quadruplex stabilizing compounds led to the activation of dormant origins of DNA replication, with preferential bi-directional pausing of replications forks moving out of the TR region, implicating the role of the G-rich TR in the perturbation of episomal DNA replication. Over time, treatment with PhenDC3 showed a loss of viral episomes in the infected cells. Overall, these data show that G-quadruplex stabilizing compounds retard the progression of replication forks leading to a reduction in DNA replication and episomal maintenance. These results suggest a potential role for G-quadruplex stabilizers in the treatment of KSHV-associated diseases.",2016 May 5,"['Madireddy, Advaitha', 'Purushothaman, Pravinkumar', 'Loosbroock, Christopher P.', 'Robertson, Erle S.', 'Schildkraut, Carl L.', 'Verma, Subhash C.']",Nucleic Acids Res,,,True
a01ff63db2589d7dec2c09c288d0fd31654be7be,PMC,G-quadruplex-interacting compounds alter latent DNA replication and episomal persistence of KSHV,http://dx.doi.org/10.1093/nar/gkw038,PMC4856979,26837574,CC BY-NC,"Kaposi's sarcoma associated herpesvirus (KSHV) establishes life-long latent infection by persisting as an extra-chromosomal episome in the infected cells and by maintaining its genome in dividing cells. KSHV achieves this by tethering its epigenome to the host chromosome by latency associated nuclear antigen (LANA), which binds in the terminal repeat (TR) region of the viral genome. Sequence analysis of the TR, a GC-rich DNA element, identified several potential Quadruplex G-Rich Sequences (QGRS). Since quadruplexes have the tendency to obstruct DNA replication, we used G-quadruplex stabilizing compounds to examine their effect on latent DNA replication and the persistence of viral episomes. Our results showed that these G-quadruplex stabilizing compounds led to the activation of dormant origins of DNA replication, with preferential bi-directional pausing of replications forks moving out of the TR region, implicating the role of the G-rich TR in the perturbation of episomal DNA replication. Over time, treatment with PhenDC3 showed a loss of viral episomes in the infected cells. Overall, these data show that G-quadruplex stabilizing compounds retard the progression of replication forks leading to a reduction in DNA replication and episomal maintenance. These results suggest a potential role for G-quadruplex stabilizers in the treatment of KSHV-associated diseases.",2016 May 5,"['Madireddy, Advaitha', 'Purushothaman, Pravinkumar', 'Loosbroock, Christopher P.', 'Robertson, Erle S.', 'Schildkraut, Carl L.', 'Verma, Subhash C.']",Nucleic Acids Res,,,False
57a30fc4f036048830b77fa87c64358c48c946d6,PMC,"First human case of avian influenza A (H5N6) in Yunnan province, China",http://dx.doi.org/10.1177/2050313X15596484,PMC4857328,27489694,CC BY-NC,"OBJECTIVE: To report clinical, virological, and epidemiological features of the first death caused by a H5N6 avian influenza virus in Yunnan Province, China. METHOD: The case was described in clinical expression, chest radiography, blood test and treatment. Real-time RT-PCR was used to detect H5N6 virus RNA in clinical and environment samples. Epidemiological investigation was performed including case exposure history determinant, close contacts follow up, and environment sample collection. RESULTS: The patient initially developed sore throat and coughs on 27 January 2015. The disease progressed to severe pneumonia, multiple organ dysfunction syndrome, and acute respiratory distress syndrome. And the patient died on 6 February. A highly pathogenic avian influenza A H5N6 virus was isolated from the tracheal aspirate specimen of the patient. The viral genome analyses revealed that the H5 hemmagglutinin gene belongs to 2.3.4.4 clade. Epidemiological investigation showed that the patient had exposure to wild bird. All close contacts of the patient did not present the same disease in seven consecutive days. A high H5 positive rate was detected in environmental samples from local live poultry markets. CONCLUSION: The findings suggest that studies on the source of the virus, transmission models, serologic investigations, vaccines, and enhancing surveillance in both humans and birds are necessary.",2015 Aug 4,"['He, Jibo', 'Duan, Jing']",SAGE Open Med Case Rep,,,True
25a10dcacb257ac926ad42124f605189b3789d3f,PMC,Research Communications of the 24th ECVIM‐CA Congress,http://dx.doi.org/10.1111/jvim.12491,PMC4858066,,CC BY-NC,,2015 Jan 10 Jan-Feb,,J Vet Intern Med,,,True
03d3f764353cecb297c318e55b88be1d5664bf5c,PMC,Critical role of ethics in clinical management and public health response to the West Africa Ebola epidemic,http://dx.doi.org/10.2147/RMHP.S83907,PMC4869630,27274326,CC BY-NC,"The devastation caused by the Ebola virus disease (EVD) outbreak in West Africa has brought to the fore a number of important ethical debates about how best to respond to a health crisis. These debates include issues related to prevention and containment, management of the health care workforce, clinical care, and research design, all of which are situated within the overarching moral problem of severe transnational disadvantage, which has very real and specific impacts upon the ability of citizens of EVD-affected countries to respond to a disease outbreak. Ethical issues related to prevention and containment include the appropriateness and scope of quarantine and isolation within and outside affected countries. The possibility of infection in health care workers impelled consideration of whether there is an obligation to provide health services where personal protection equipment is inadequate, alongside the issue of whether the health care workforce should have special access to experimental treatment and care interventions under development. In clinical care, ethical issues include the standards of care owed to people who comply with quarantine and isolation restrictions. Ethical issues in research include appropriate study design related to experimental vaccines and treatment interventions, and the sharing of data and biospecimens between research groups. The compassionate use of experimental drugs intersects both with research ethics and clinical care. The role of developed countries also came under scrutiny, and we concluded that developed countries have an obligation to contribute to the containment of EVD infection by contributing to the strengthening of local health care systems and infrastructure in an effort to provide fair benefits to communities engaged in research, ensuring that affected countries have ready and affordable access to any therapeutic or preventative interventions developed, and supporting affected countries on their way to recovery from the impact of EVD on their social and economic lives.",2016 May 12,"['Folayan, Morenike O', 'Haire, Bridget G', 'Brown, Brandon']",Risk Manag Healthc Policy,,,True
67d017d4dfeac56abe259135d80211a9092a1e73,PMC,Interventions in live poultry markets for the control of avian influenza: A systematic review,http://dx.doi.org/10.1016/j.onehlt.2016.03.002,PMC4871622,27213177,CC BY-NC-ND,"BACKGROUND: Live poultry markets (LPMs) pose a threat to public health by promoting the amplification and dissemination of avian influenza viruses (AIVs) and by providing the ideal setting for zoonotic influenza transmission. OBJECTIVE: This review assessed the impact of different interventions implemented in LPMs to control the emergence of zoonotic influenza. METHODS: Publications were identified through a systematic literature search in the PubMed, MEDLINE and Web of Science databases. Eligible studies assessed the impact of different interventions, such as temporary market closure or a ban on holding poultry overnight, in reducing i) AIV-detection rates in birds and the market environment or ii) influenza incidence in humans. Unpublished literature, reviews, editorials, cross-sectional studies, theoretical models and publications in languages other than English were excluded. Relevant findings were extracted and critically evaluated. For the comparative analysis of findings across studies, standardized outcome measures were computed as i) the relative risk reduction (RRR) of AIV-detection in LPMs and ii) incidence rate ratios (IRRs) of H7N9-incidence in humans. RESULTS: A total of 16 publications were identified and reviewed. Collectively, the data suggest that AIV-circulation can be significantly reduced in the LPM-environment and among market-birds through (i) temporary LPM closure, (ii) periodic rest days (iii) market depopulation overnight and (iv) improved hygiene and disinfection. Overall, the findings indicate that the length of stay of poultry in the market is a critical control point to interrupt the AIV-replication cycle within LPMs. In addition, temporary LPM closure was associated with a significant reduction of the incidence of zoonotic influenza. The interpretation of these findings is limited by variations in the implementation of interventions. In addition, some of the included studies were of ecologic nature or lacked an inferential framework, which might have lead to cosiderable confounding and bias. CONCLUSIONS: The evidence collected in this review endorses permanent LPM-closure as a long-term objective to reduce the zoonotic risk of avian influenza, although its economic and socio-political implications favour less drastic interventions, e.g. weekly rest days, for implementation in the short-term.",2016 Mar 22,"['Offeddu, Vittoria', 'Cowling, Benjamin J.', 'Peiris, J.S. Malik']",One Health,,,False
c7d39cd61dd94cb21128f5c07392786f2c9a5d2a,PMC,A recombinant nucleocapsid protein-based indirect enzyme-linked immunosorbent assay to detect antibodies against porcine deltacoronavirus,http://dx.doi.org/10.1292/jvms.15-0533,PMC4873850,26668175,CC BY-NC-ND,"Recently, porcine deltacoronavirus (PDCoV) has been proven to be associated with enteric disease in piglets. Diagnostic tools for serological surveys of PDCoV remain in the developmental stage when compared with those for other porcine coronaviruses. In our study, an indirect enzyme-linked immunosorbent assay (ELISA) (rPDCoV-N-ELISA) was developed to detect antibodies against PDCoV using a histidine-tagged recombinant nucleocapsid (N) protein as an antigen. The rPDCoV-N-ELISA did not cross-react with antisera against porcine epidemic diarrhea virus, swine transmissible gastroenteritis virus, porcine group A rotavirus, classical swine fever virus, porcine circovirus-2, porcine pseudorabies virus, and porcine reproductive and respiratory syndrome virus; the receiver operating characteristic (ROC) curve analysis revealed 100% sensitivity and 90.4% specificity of the rPDCoV-N-ELISA based on samples of known status (n=62). Analyses of field samples (n=319) using the rPDCoV-N-ELISA indicated that 11.59% of samples were positive for antibodies against PDCoV. These data demonstrated that the rPDCoV-N-ELISA can be used for epidemiological investigations of PDCoV and that PDCoV had a low serum prevalence in pig population in Heilongjiang province, northeast China.",2016 Apr 13,"['SU, Mingjun', 'LI, Chunqiu', 'GUO, Donghua', 'WEI, Shan', 'WANG, Xinyu', 'GENG, Yufei', 'YAO, Shuang', 'GAO, Jing', 'WANG, Enyu', 'ZHAO, Xiwen', 'WANG, Zhihui', 'WANG, Jianfa', 'WU, Rui', 'FENG, Li', 'SUN, Dongbo']",J Vet Med Sci,,,True
e1e8903986998f998a4ee66cbbf1c0b05ebf2eb1,PMC,"Optimized Expression, Purification of Herpes B Virus gD Protein in Escherichia coli, and Production of Its Monoclonal Antibodies",http://dx.doi.org/10.5812/jjm.32183,PMC4877525,27226876,CC BY-NC,"BACKGROUND: Herpes B virus (BV) is a zoonotic disease caused by double-stranded enveloped DNA virus with cercopithecidae as its natural host. The mortality rate of infected people could be up to 70% with fatal encephalitis and encephalomyelitis. Up to now, there are no effective treatments for BV infection. Among the various proteins encoded by monkey B virus, gD, a conserved structural protein, harbors important application value for serological diagnosis of frequent variations of the monkey B virus. OBJECTIVES: This study aimed to expressed the gD protein of BV in Escherichia coli by a recombinant vector, and prepare specific monoclonal antibodies against gD of BV to pave the way for effective and quick diagnosis reagent research. MATERIALS AND METHODS: The gD gene of BV was optimized by OptimWiz to improve codon usage bias and synthesis, and the recombinant plasmid, pET32a/gD, was constructed and expressed in E. coli Rosetta (DE3). The expressed fusion protein, His-gD, was purified and the BALB/c mice were immunized by this protein. Spleen cells from the immunized mice and SP2/0 myeloma cells were fused together, and the monoclonal cell strains were obtained by indirect enzyme-linked immunosorbent assay (ELISA) screening, followed by preparation of monoclonal antibody ascetic fluid. RESULTS: The optimized gD protein was highly expressed in E. coli and successfully purified. Five monoclonal antibodies (mAbs) against BV were obtained and named as 4E3, 3F8, 3E7, 1H3 and 4B6, and with ascetic fluid titers of 2 × 10(6), 2 × 10(5), 2 × 10(5), 2 × 10(3) and 2 × 10(2), respectively. The 1H3 and 4E3 belonged to the IgG2b subclass, while 3E7, 3F8 and 4B6 belonged to the IgG1 subclass. CONCLUSIONS: The cell lines obtained in this work secreted potent, stable and specific anti-BV mAbs, which were suitable for the development of herpes B virus diagnosis reagents.",2016 Mar 12,"['Jin, Zian', 'Sun, Tao', 'Xia, Xueshan', 'Wei, Qiujiang', 'Song, Yuzhu', 'Han, Qinqin', 'Chen, Qiang', 'Hu, Juan', 'Zhang, Jinyang']",Jundishapur J Microbiol,,,True
40e22da9b80c58635cb6675194f4cb7b937a044c,PMC,First genome sequences of buffalo coronavirus from water buffaloes in Bangladesh,http://dx.doi.org/10.1016/j.nmni.2016.02.011,PMC4879238,27274850,CC BY-NC-ND,"We report the complete genome sequences of a buffalo coronavirus (BufCoV HKU26) detected from the faecal samples of two domestic water buffaloes (Bubalus bubalis) in Bangladesh. They possessed 98–99% nucleotide identities to bovine coronavirus (BCoV) genomes, supporting BufCoV HKU26 as a member of Betacoronavirus 1. Nevertheless, BufCoV HKU26 possessed distinct accessory proteins between spike and envelope compared to BCoV. Sugar-binding residues in the N-terminal domain of S protein in BCoV are conserved in BufCoV HKU26.",2016 Mar 3,"['Lau, S.K.P.', 'Tsang, A.K.L.', 'Shakeel Ahmed, S.', 'Mahbub Alam, M.', 'Ahmed, Z.', 'Wong, P.-C.', 'Yuen, K.-Y.', 'Woo, P.C.Y.']",New Microbes New Infect,,,False
1e16ae8d036d8775c165e3e64235f90042d59a37,PMC,"Health response to Hajj mass gathering from emergency perspective, narrative review",http://dx.doi.org/10.1016/j.tjem.2015.02.001,PMC4882208,27239622,CC BY-NC-ND,"Hajj is a unique gathering with Mecca and Kaaba being spiritually important to many faiths across the globe, especially Muslims. This is because of the proclamation of the prophet's father, Ibrahaam, when he called all mankind to perform Hajj. That is why all Muslims on Earth feel that they have to visit Mecca and Kaaba on a specific date and time, and that is the reason this small location hosts one of the largest human gatherings in the world. Hajj is one of the five pillars of Islam that every financially and physically able Muslim must perform once in his/her lifetime. For 14 centuries countless millions of Muslim men and women from the four corners of the earth have undertaken pilgrimage to Mecca. In conclusion this review article confirm that Hajj is oldest and largest mass gathering in all mankind and there is some issues influence the health response such as size of gathering. diversity of population, climate and health facilities around hajj site, also we discuss the infectious and non infectious related illness in hajj and their prevention methods.",2016 Mar 9,"['Shujaa, Asaad', 'Alhamid, Sameer']",Turk J Emerg Med,,,False
1fe9d44383ae2debf062555ea05a816dd3848a91,PMC,"Challenges presented by MERS corona virus, and SARS corona virus to global health",http://dx.doi.org/10.1016/j.sjbs.2016.02.019,PMC4890194,27298584,CC BY-NC-ND,"Numerous viral infections have arisen and affected global healthcare facilities. Millions of people are at severe risk of acquiring several evolving viral infections through several factors. In the present article we have described about risk factors, chance of infection, and prevention methods of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV), human coronaviruses (CoVs) frequently cause a normal cold which is mild and self-restricting. Zoonotic transmission of CoVs such as the newly discovered MERS-CoV and SARS-CoV, may be associated with severe lower respiratory tract infection. The present review provides the recent clinical and pathological information on MERS and SARS. The task is to transform these discoveries about MERS and SARS pathogenesis and to develop intervention methods that will eventually allow the effective control of these recently arising severe viral infections. Global health sector has learnt many lessons through the recent outbreak of MERS and SARS, but the need for identifying new antiviral treatment was not learned. In the present article we have reviewed the literature on the several facets like transmission, precautions and effectiveness of treatments used in patients with MERS-CoV and SARS infections.",2016 Jul 21,"Al-Hazmi, Ali",Saudi J Biol Sci,,,False
e67d4c945d10fe5783c1289f45611cec25143564,PMC,Emergency cesarean section in an epidemic of the middle east respiratory syndrome: a case report,http://dx.doi.org/10.4097/kjae.2016.69.3.287,PMC4891544,27274377,CC BY-NC,"Only a few reports have been published on women with an infectious respiratory viral pathogen, such as Middle East Respiratory Syndrome (MERS) Coronavirus delivering a baby. A laboratory confirmed case of MERS was reported during a MERS outbreak in the Republic of Korea in a woman at gestational week 35 + 4. She recovered, and delivered a healthy baby by emergency cesarean section (C-sec). We present the clinical course and the emergency C-sec in a pregnant woman with MERS.",2016 Jun 1,"['Park, Mi Hye', 'Kim, Hee Ryun', 'Choi, Duck Hwan', 'Sung, Ji Hee', 'Kim, Jong Hwa']",Korean J Anesthesiol,,,True
85dfb59af4c4ec824f1f62c645e5b91a6e3cc814,PMC,2015 ACVIM Forum Research Abstract Program,http://dx.doi.org/10.1111/jvim.12609,PMC4895366,,CC BY-NC,,2015 May 27 Jul-Aug,,J Vet Intern Med,,,True
a6e1fee252ceebcf3f2285e84dc0b26fc7305d8b,PMC,2015 ACVIM Forum Research Reports Program,http://dx.doi.org/10.1111/jvim.13002,PMC4895374,,CC BY-NC,,2015 Jun 12 Jul-Aug,,J Vet Intern Med,,,False
1ca4dc2cbd2171a1b471d103caa4bb5d1f057eef,PMC,A Randomized Clinical Trial Evaluating Metabolism of Colostral and Plasma Derived Immunoglobulin G in Jersey Bull Calves,http://dx.doi.org/10.1111/jvim.12586,PMC4895413,25858814,CC BY-NC,"BACKGROUND: Intravenous plasma administration has been recommended in healthy or sick calves with failure of passive immunity. HYPOTHESIS: IV administered plasma‐derived immunoglobulin G (IgG) undergoes increased catabolism as reflected by a rapid decrease in serum IgG concentration with an increase in fecal IgG concentrations within 48 h. ANIMALS: Thirty newborn Jersey calves. Fifteen were fed colostrum (CL group) and 15 were given bovine plasma IV (PL group). MATERIALS AND METHODS: Randomized clinical trial. Calves in the CL group were fed 3 L of colostrum once, by oroesophageal tubing. Calves in the PL group were given plasma IV at a dosage of 34 mL/kg. Serum and fecal samples were collected at 0 h, 6 h, 12 h, 48 h, 5 d, and 7 d. Serum and fecal IgG concentrations were determined by radial immunodiffusion. RESULTS: Calves in the CL group maintained serum IgG concentrations consistent with adequate transfer of immunity (≥1,000 mg/dL) throughout the study period. Calves in the PL group achieved median IgG concentrations of ≥1,000 mg/dL at 6 h but the concentrations were <1,000 mg/dL by 12 h. Calves in the PL group were 5 times more likely to experience mortality compared to the CL group (hazard ratio = 5.01). Fecal IgG concentrations were not different between the 2 groups during the first 48 h (P > .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Catabolism of plasma derived IgG occurs rapidly during the first 12 h after transfusion. Fecal excretion did not explain the fate of the plasma derived IgG.",2015 Apr 9 May-Jun,"['Pipkin, K.M.', 'Hagey, J.V.', 'Rayburn, M.C.', 'Chigerwe, M.']",J Vet Intern Med,,,True
04c77d3ae97fcb0cb3d82480c5f75513f6266662,PMC,Co‐infections with Respiratory Viruses in Dogs with Bacterial Pneumonia,http://dx.doi.org/10.1111/jvim.12553,PMC4895503,25818209,CC BY-NC,"BACKGROUND: Bacterial pneumonia (BP) is an inflammation of the lower airways and lung parenchyma secondary to bacterial infection. The pathogenesis of BP in dogs is complex and the role of canine respiratory viruses has not been fully evaluated. OBJECTIVES: The aim of this study was to investigate the occurrence of viral co‐infections in dogs with BP and to assess demographic or clinical variables as well as disease severity associated with viral co‐infections. ANIMALS: Twenty household dogs with BP caused by opportunistic bacteria and 13 dogs with chronic (>30 days) tracheobronchitis caused by Bordetella bronchiseptica (BBTB). METHODS: Prospective cross‐sectional observational study. Diagnosis was confirmed by clinical and laboratory findings, diagnostic imaging, and cytologic and microbiologic analysis of bronchoalveolar lavage or transtracheal wash fluid. Canine parainfluenza virus (CPIV), canine adenovirus, canine herpes virus, canine influenzavirus, canine distemper virus, canine respiratory coronavirus (CRCoV) and canine pneumovirus, as well as B. bronchiseptica and Mycoplasma spp. were analyzed in respiratory samples using PCR assays. RESULTS: CPIV was detected in 7/20 and CRCoV in 1/20 dogs with BP. Respiratory viruses were not detected in dogs with BBTB. There were no significant differences in clinical variables between BP dogs with and without a viral co‐infection. CONCLUSION AND CLINICAL IMPORTANCE: Respiratory viruses were found frequently in dogs with BP and may therefore play an important role in the etiology and pathogenesis of BP. Clinical variables and disease severity did not differ between BP dogs with and without viral co‐infection.",2015 Mar 27 Mar-Apr,"['Viitanen, S.J.', 'Lappalainen, A.', 'Rajamäki, M.M.']",J Vet Intern Med,,,True
3062fc222bccc8c520612d9d6c9b91f048be12b8,PMC,Propagation of Human Embryonic Stem Cells on Human Amniotic Fluid Cells as Feeder Cells in Xeno-Free Culture Conditions,http://dx.doi.org/10.12717/DR.2016.20.1.063,PMC4899559,27294211,CC BY-NC,"Human embryonic stem cells (hESCs) have been routinely cultured on mouse embryonic fibroblast feederlayers with a medium containing animal materials. For clinical application of hESCs, animal-derived products from the animal feeder cells, animal substrates such as gelatin or Matrigel and animal serum are strictly to be eliminated in the culture system. In this study, we performed that SNUhES32 and H1 were cultured on human amniotic fluid cells (hAFCs) with KOSR XenoFree and a humanized substrate. All of hESCs were relatively well propagated on hAFCs feeders with xeno-free conditions and they expressed pluripotent stem cell markers, alkaline phosphatase, SSEA-4, TRA1-60, TRA1-81, Oct-4, and Nanog like hESCs cultured on STO or human foreskin fibroblast feeders. In addition, we observed the expression of nonhuman N-glycolylneuraminic acid (Neu5GC) molecules by flow cytometry, which was xenotransplantation components of contamination in hESCs cultured on animal feeder conditions, was not detected in this xeno-free condition. In conclusion, SNUhES32 and H1 could be maintained on hAFCs for humanized culture conditions, therefore, we suggested that new xenofree conditions for clinical grade hESCs culture will be useful data in future clinical studies.",2016 Mar,"['Jung, Juwon', 'Baek, Jin Ah', 'Seol, Hye Won', 'Choi, Young Min']",Dev Reprod,,,True
8b78861684f93b6c17ed9e9d18027cfc12c41644,PMC,Cirrhosis is a risk factor for total hip arthroplasty for avascular necrosis: A Danish nationwide cohort study,http://dx.doi.org/10.3109/17453674.2016.1151122,PMC4900083,26900635,CC BY-NC,"BACKGROUND AND PURPOSE: There are limited data on risk factors for avascular necrosis of the hip, but cirrhosis has been proposed as a risk factor. We examined the association between cirrhosis and incidence of total hip arthroplasty for avascular necrosis. METHODS: We used nationwide healthcare data to identify all Danish residents diagnosed with cirrhosis in 1994–2011, and matched them 1:5 by age and sex to non-cirrhotic reference individuals from the general population. We excluded people with a previous total hip arthroplasty, a previous hip fracture, or a previous diagnosis of avascular necrosis. We used stratified Cox regression to estimate the hazard ratio (HR) for cirrhosis patients relative to reference individuals, adjusting for potential confounders. We used the cumulative incidence function to compute 5-year risks. RESULTS: We included 25,421 cirrhosis patients and 114,052 reference individuals. Their median age was 57 years, and 65% were men. 45 cirrhosis patients and 44 reference individuals underwent total hip arthroplasty for avascular necrosis. Cirrhosis patients’ HR for a total hip arthroplasty for avascular necrosis was 10 (95% CI: 6–17), yet their 5-year risk of avascular necrosis was only 0.2%. For the reference individuals, the 5-year risk was 0.02%. INTERPRETATION: Cirrhosis is a strong risk factor for avascular necrosis of the hip, but it is rare even in cirrhosis patients.",2016 Jun 12,"['Deleuran, Thomas', 'Overgaard, Søren', 'Vilstrup, Hendrik', 'Jepsen, Peter']",Acta Orthop,,,True
f9476a333c17961ff4cc34b45f4b2da5ed29457f,PMC,Ad Hoc Influenza Vaccination During Years of Significant Antigenic Drift in a Tropical City With 2 Seasonal Peaks: A Cross-Sectional Survey Among Health Care Practitioners,http://dx.doi.org/10.1097/MD.0000000000003359,PMC4902475,27175633,CC BY-ND,"We evaluated the acceptability of an additional ad hoc influenza vaccination among the health care professionals following seasons with significant antigenic drift. Self-administered, anonymous surveys were performed by hard copy questionnaires in public hospitals, and by an on-line platform available to all healthcare professionals, from April 1st to May 31st, 2015. A total of 1290 healthcare professionals completed the questionnaires, including doctors, nurses, and allied health professionals working in both the public and private systems. Only 31.8% of participating respondents expressed an intention to receive the additional vaccine, despite that the majority of them agreed or strongly agreed that it would bring benefit to the community (88.9%), save lives (86.7%), reduce medical expenses (76.3%), satisfy public expectation (82.8%), and increase awareness of vaccination (86.1%). However, a significant proportion expressed concern that the vaccine could disturb the normal immunization schedule (45.5%); felt uncertain what to do in the next vaccination round (66.0%); perceived that the summer peak might not occur (48.2%); and believed that the summer peak might not be of the same virus (83.5%). Furthermore, 27.8% of all respondents expected that the additional vaccination could weaken the efficacy of previous vaccinations; 51.3% was concerned about side effects; and 61.3% estimated that there would be a low uptake rate. If the supply of vaccine was limited, higher priority groups were considered to include the elderly aged ≥65 years with chronic medical conditions (89.2%), the elderly living in residential care homes (87.4%), and long-stay residents of institutions for the disabled (80.7%). The strongest factors associated with accepting the additional vaccine included immunization with influenza vaccines in the past 3 years, higher perceived risk of contracting influenza, and higher perceived severity of the disease impact. The acceptability to an additional ad hoc influenza vaccination was low among healthcare professionals. This could have a negative impact on such additional vaccination campaigns since healthcare professionals are a key driver for vaccine acceptance. The discordance in perceived risk and acceptance of vaccination regarding self versus public deserves further evaluation.",2016 May 13,"['Wong, Martin C.S.', 'Nelson, E. Anthony S.', 'Leung, Czarina', 'Lee, Nelson', 'Chan, Martin C.W.', 'Choi, Kin Wing', 'Rainer, Timothy H.', 'Cheng, Frankie W.T.', 'Wong, Samuel Y.S.', 'Lai, Christopher K.C.', 'Lam, Bosco', 'Cheung, Tak Hong', 'Leung, Ting Fan', 'Chan, Paul K.S.']",Medicine (Baltimore),,,True
57d3826bb67ec3a479bc58f5e9210de44845b802,PMC,Detection of infectious bronchitis virus strains similar to Japan in Taiwan,http://dx.doi.org/10.1292/jvms.15-0609,PMC4905846,26822119,CC BY-NC-ND,"A total of 1,320 tracheal samples from 66 broiler flocks sent to slaughterhouses and 42 tracheal samples from 42 flocks of local chickens in the field were collected for infectious bronchitis virus (IBV) gene detection by reverse transcription polymerase chain reaction using nucleocapsid-specific primers and spike-specific primers. Prevalence in broiler flocks was 39.4% (26/66) and in local chicken flocks was 11.9% (5/42). Several IBVs similar to Japan were detected in Taiwan. One-direction neutralization revealed that the reference antisera did not offer protection against the IBVs similar to those from Japan.",2016 May 29,"['TSAI, Cheng-Ta', 'TSAI, Hsin-Fu', 'WANG, Ching-Ho']",J Vet Med Sci,,,True
48a94a1e8511bc77ae8d01af2f0c5dab4dc73cd6,PMC,Two Epidemics and Global Health Security Agenda,http://dx.doi.org/10.1016/j.phrp.2015.12.008,PMC4907785,27429900,CC BY-NC-ND,,2015 Dec 17,"['Cho, Hae-Wol', 'Chu, Chaeshin']",Osong Public Health Res Perspect,,,False
59f43728701d0747e4f79309a62d2416b3564f2b,PMC,Global Health Security: The Lessons from the West African Ebola Virus Disease Epidemic and MERS Outbreak in the Republic of Korea,http://dx.doi.org/10.1016/j.phrp.2015.12.006,PMC4907786,27429901,CC BY-NC-ND,"The Ebola virus disease outbreak in West Africa and the Middle East Respiratory Syndrome outbreak in the Republic of Korea have given huge impacts in different aspects. Health security is no more a new coinage. Global health security became more realistic in its practical application. In the perspective of global health, it will be helpful to peruse lessons learned from the Ebola outbreak in West Africa and MERS outbreak in Korea.",2015 Dec 17,GHSA Preparation Task Force Team,Osong Public Health Res Perspect,,,False
4001bc47c8c30f370e59b5d26a74187b1727cc5b,PMC,Round-up of GHSA Steering Group and Action Packages in 2015,http://dx.doi.org/10.1016/j.phrp.2015.12.007,PMC4907787,27429902,CC BY-NC-ND,"All Global Health Security Agenda (GHSA) Steering Group Members remain strongly committed to accelerating measurable progress and implementing concrete commitments toward a world safe and secure from infectious disease threats, recognizing the devastation of the Ebola epidemic and the clear interdependence of health in the 21(st) century. All GHSA Steering Group members reinforced that GHSA is supportive of International Health Regulations implementation, as well as components of other global health security frameworks such as the World Organization for Animal Health Performance of Veterinary Services pathway. The GHSA will continue to focus on multilateral engagement. The GHSA Steering Group is committed to engaging non-state actors and agreed to discuss next steps toward engaging the private sector.",2015 Dec 17,"['GHSA Steering Group Secretariat', 'GHSA Preparation Task Force Team']",Osong Public Health Res Perspect,,,False
0a1f43c04e0e22fb6efbd94611920bc9680d7ae3,PMC,TNF-α − 308 G > A and IFN-γ + 874 A > T gene polymorphisms in Egyptian patients with lupus erythematosus,http://dx.doi.org/10.1016/j.mgene.2016.06.002,PMC4909826,27331019,CC BY-NC-ND,"BACKGROUND: Systemic lupus erythematosus (SLE) is associated with immunogenetic factors. This study was planned to test for the association of TNF-α − 308 and IFN-γ + 874 gene polymorphisms with susceptibility and severity of SLE in Egyptian cases. SUBJECTS AND METHODS: This is a case controlled study including 125 Egyptian cases with SLE in addition to 112 healthy unrelated individuals from the same locality. For all participants, TNF-α − 308 G > A and IFN-γ + 874 A > T genetic polymorphisms were characterized using the PCR technique. RESULTS: Cases with SLE showed a significantly higher TNF-α − 308 A allele carriage rate (AA + GA genotypes) compared to controls (26.4% vs. 12.5%, p = 0.009, OR = 2.51, 95% CI = 1.26–4.99). These cases showed also a significantly higher carriage rate for the IFN-γ + 874 T allele (AT + TT genotypes) compared to controls (47.2% vs. 32.1%, p = 0.02, OR = 1.89, 95% CI = 1.11–3.21). Comparing age, gender, and disease severity presented by nephritis class, activity and chronicity indices in cases carrying the TNF-α − 308 A allele and in cases carrying IFN-γ + 874 T allele versus others showed no significant difference (p > 0.05). CONCLUSIONS: TNF-α − 308 A and IFN-γ + 874 T allele carriage are associated with susceptibility but not severity of SLE in Egyptian subjects.",2016 Jun 4,"['Al-Kholy, Wfaa', 'Elsaid, Afaf', 'Sleem, Aml', 'Fathy, Hend', 'Elshazli, Rami', 'Settin, Ahmad']",Meta Gene,,,False
0519d1d90353abf1d2a97d4fea15d24d48cf1fbd,PMC,Communicable Diseases and Outbreak Control,http://dx.doi.org/10.5505/1304.7361.2015.19970,PMC4910139,27437528,CC BY-NC-ND,"Infectious disease during an emergency condition can raise the death rate 60 times in comparison to other causes including trauma. An epidemic, or outbreak, can occur when several aspects of the agent (pathogen), population (hosts), and the environment create an ideal situation for spread. Overcrowding, poor regional design and hygiene due to poverty, dirty drinking water, rapid climate changes, and natural disasters, can lead to conditions that allow easier transmission of disease. Once it has been established that an emergency condition exists, there must be a prompt and thorough response for communicable disease control. A camp should be created, and the disease managed rapidly. The overall goals are rapid assessment, prevention, surveillance, outbreak control, and disease management.",2016 Mar 9,"AMELI, Jonathan",Turk J Emerg Med,,,False
3b09cf3b8cc59b5d16c4717c50ffa70edb467046,PMC,"Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review",http://dx.doi.org/10.1002/ppul.23304,PMC4912005,26418604,CC BY-NC-ND,"Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, rare lung disease resulting in chronic oto‐sino‐pulmonary disease in both children and adults. Many physicians incorrectly diagnose PCD or eliminate PCD from their differential diagnosis due to inexperience with diagnostic testing methods. Thus far, all therapies used for PCD are unproven through large clinical trials. This review article outlines consensus recommendations from PCD physicians in North America who have been engaged in a PCD centered research consortium for the last 10 years. These recommendations have been adopted by the governing board of the PCD Foundation to provide guidance for PCD clinical centers for diagnostic testing, monitoring, and appropriate short and long‐term therapeutics in PCD patients. Pediatr Pulmonol. 2016;51:115–132. © 2015 The Authors. Pediatric Pulmonology Published by Wiley Periodicals, Inc.",2016 Feb 29,"['Shapiro, Adam J.', 'Zariwala, Maimoona A.', 'Ferkol, Thomas', 'Davis, Stephanie D.', 'Sagel, Scott D.', 'Dell, Sharon D.', 'Rosenfeld, Margaret', 'Olivier, Kenneth N.', 'Milla, Carlos', 'Daniel, Sam J.', 'Kimple, Adam J.', 'Manion, Michele', 'Knowles, Michael R.', 'Leigh, Margaret W.', None]",Pediatr Pulmonol,,,True
6d479d399ca496281c8dccc3198cb86d965deb1e,PMC,ECEIM Congress 2015,http://dx.doi.org/10.1111/jvim.13925,PMC4913562,,CC BY-NC,,2016 Apr 1 May-Jun,,J Vet Intern Med,,,True
b616293107ee48ebc8884fc55ebc66965df4feb8,PMC,Research Communications of the 25th ECVIM‐CA Congress,http://dx.doi.org/10.1111/jvim.13647,PMC4913621,,CC BY-NC,,2016 Nov 9 Jan-Feb,,J Vet Intern Med,,,True
12267e4378cb6c21255f204fb40b9daaa02ab09b,PMC,"Adenovirus 2, Bordetella bronchiseptica, and Parainfluenza Molecular Diagnostic Assay Results in Puppies After vaccination with Modified Live Vaccines",http://dx.doi.org/10.1111/jvim.13821,PMC4913651,26692461,CC BY-NC,"BACKGROUND: Canine adenovirus 2, parainfluenza, and Bordetella bronchiseptica cause respiratory disease in dogs, and each has a modified live intranasal vaccine available. Molecular diagnostic assays to amplify specific nucleic acids are available for each of these agents. If positive molecular diagnostic assay results are common after vaccination, the positive predictive value of the diagnostic assays for disease would be decreased. OBJECTIVE: To determine the impact of administration of commercially available modified live topical adenovirus 2, B. bronchiseptica, and parainfluenza vaccine has on the results of a commercially available PCR panel. ANIMALS: Eight puppies from a research breeding facility negative for these pathogens. METHODS: Blinded prospective pilot study. Puppies were vaccinated with a single dose of modified live topical adenovirus 2, B. bronchiseptica, and parainfluenza and parenteral dose of adenovirus 2, canine distemper virus, and parvovirus. Nasal and pharyngeal swabs were collected on multiple days and submitted for PCR assay. RESULTS: Nucleic acids of all 3 organisms contained in the topical vaccine were detected from both samples multiple times through 28 days after vaccination with higher numbers of positive samples detected between days 3 and 10 after vaccination. CONCLUSIONS AND CLINICAL IMPORTANCE: Vaccine status should be considered when interpreting respiratory agent PCR results if modified live vaccines have been used. Development of quantitative PCR and wild‐type sequencing are necessary to improve positive predictive value of these assays by distinguishing vaccinate from natural infection.",2016 Dec 22 Jan-Feb,"['Ruch‐Gallie, R.', 'Moroff, S.', 'Lappin, M.R.']",J Vet Intern Med,,,True
8016c07acf423bde29ea3e2742fb37286a9b013a,PMC,Update on Canine and Feline Blood Donor Screening for Blood‐Borne Pathogens,http://dx.doi.org/10.1111/jvim.13823,PMC4913655,26806261,CC BY-NC,"An update on the 2005 American College of Veterinary Internal Medicine (ACVIM) Consensus Statement on blood donor infectious disease screening was presented at the 2015 ACVIM Forum in Indianapolis, Indiana, followed by panel and audience discussion. The updated consensus statement is presented below. The consensus statement aims to provide guidance on appropriate blood‐borne pathogen testing for canine and feline blood donors in North America.",2016 Jan 25 Jan-Feb,"['Wardrop, K.J.', 'Birkenheuer, A.', 'Blais, M.C.', 'Callan, M.B.', 'Kohn, B.', 'Lappin, M.R.', 'Sykes, J.']",J Vet Intern Med,,,True
71195817c4cfe2c8b7bc13418d2062226a71d0e9,PMC,One Health stakeholder and institutional analysis in Kenya,http://dx.doi.org/10.3402/iee.v6.31191,PMC4916260,27330042,CC BY-NC,"INTRODUCTION: One Health (OH) can be considered a complex emerging policy to resolve health issues at the animal–human and environmental interface. It is expected to drive system changes in terms of new formal and informal institutional and organisational arrangements. This study, using Rift Valley fever (RVF) as a zoonotic problem requiring an OH approach, sought to understand the institutionalisation process at national and subnational levels in an early adopting country, Kenya. MATERIALS AND METHODS: Social network analysis methodologies were used. Stakeholder roles and relational data were collected at national and subnational levels in 2012. Key informants from stakeholder organisations were interviewed, guided by a checklist. Public sector animal and public health organisations were interviewed first to identify other stakeholders with whom they had financial, information sharing and joint cooperation relationships. Visualisation of the OH social network and relationships were shown in sociograms and mathematical (degree and centrality) characteristics of the network summarised. RESULTS AND DISCUSSION: Thirty-two and 20 stakeholders relevant to OH were identified at national and subnational levels, respectively. Their roles spanned wildlife, livestock, and public health sectors as well as weather prediction. About 50% of national-level stakeholders had made significant progress on OH institutionalisation to an extent that formal coordination structures (zoonoses disease unit and a technical working group) had been created. However, the process had not trickled down to subnational levels although cross-sectoral and sectoral collaborations were identified. The overall binary social network density for the stakeholders showed that 35 and 21% of the possible ties between the RVF and OH stakeholders existed at national and subnational levels, respectively, while public health actors’ collaborations were identified at community/grassroots level. We recommend extending the OH network to include the other 50% stakeholders and fostering of the process at subnational-level building on available cross-sectoral platforms.",2016 Jun 20,"['Kimani, Tabitha', 'Ngigi, Margaret', 'Schelling, Esther', 'Randolph, Tom']",Infect Ecol Epidemiol,,,True
6e1cd91f28e6a422438a943b5ef37b9911ddad2c,PMC,A Role for IFITM Proteins in Restriction of Mycobacterium tuberculosis Infection,http://dx.doi.org/10.1016/j.celrep.2015.09.048,PMC4916766,26565900,CC BY-NC-ND,"The interferon (IFN)-induced transmembrane (IFITM) proteins are critical mediators of the host antiviral response. Here, we expand the role of IFITM proteins to host defense against intracellular bacterial infection by demonstrating that they restrict Mycobacterium tuberculosis (MTb) intracellular growth. Simultaneous knockdown of IFITM1, IFITM2, and IFITM3 by RNAi significantly enhances MTb growth in human monocytic and alveolar/epithelial cells, whereas individual overexpression of each IFITM impairs MTb growth in these cell types. Furthermore, MTb infection, Toll-like receptor 2 and 4 ligands, and several proinflammatory cytokines induce IFITM1–3 gene expression in human myeloid cells. We find that IFITM3 co-localizes with early and, in particular, late MTb phagosomes, and overexpression of IFITM3 enhances endosomal acidification in MTb-infected monocytic cells. These findings provide evidence that the antiviral IFITMs participate in the restriction of mycobacterial growth, and they implicate IFITM-mediated endosomal maturation in its antimycobacterial activity.",2015 Nov 3,"['Ranjbar, Shahin', 'Haridas, Viraga', 'Jasenosky, Luke D.', 'Falvo, James V.', 'Goldfeld, Anne E.']",Cell Rep,,,True
93ee83d6c6e7014e02c1231e5bc0e8075c276fbf,PMC,A Role for IFITM Proteins in Restriction of Mycobacterium tuberculosis Infection,http://dx.doi.org/10.1016/j.celrep.2015.09.048,PMC4916766,26565900,CC BY-NC-ND,"The interferon (IFN)-induced transmembrane (IFITM) proteins are critical mediators of the host antiviral response. Here, we expand the role of IFITM proteins to host defense against intracellular bacterial infection by demonstrating that they restrict Mycobacterium tuberculosis (MTb) intracellular growth. Simultaneous knockdown of IFITM1, IFITM2, and IFITM3 by RNAi significantly enhances MTb growth in human monocytic and alveolar/epithelial cells, whereas individual overexpression of each IFITM impairs MTb growth in these cell types. Furthermore, MTb infection, Toll-like receptor 2 and 4 ligands, and several proinflammatory cytokines induce IFITM1–3 gene expression in human myeloid cells. We find that IFITM3 co-localizes with early and, in particular, late MTb phagosomes, and overexpression of IFITM3 enhances endosomal acidification in MTb-infected monocytic cells. These findings provide evidence that the antiviral IFITMs participate in the restriction of mycobacterial growth, and they implicate IFITM-mediated endosomal maturation in its antimycobacterial activity.",2015 Nov 3,"['Ranjbar, Shahin', 'Haridas, Viraga', 'Jasenosky, Luke D.', 'Falvo, James V.', 'Goldfeld, Anne E.']",Cell Rep,,,False
89122ac5b68dcc5252569b3be17c47f66385b7fb,PMC,"Population-based Surveillance for Medically Attended Human Parainfluenza Viruses From the Influenza Incidence Surveillance Project, 2010–2014",http://dx.doi.org/10.1097/INF.0000000000001140,PMC4927308,26974891,CC BY-NC-ND,"BACKGROUND: Parainfluenza viruses (PIV) have been shown to contribute substantially to pediatric hospitalizations in the United States. However, to date, there has been no systematic surveillance to estimate the burden among pediatric outpatients. METHODS: From August 2010 through July 2014, outpatient health care providers with enumerated patient populations in 13 states and jurisdictions participating in the Influenza Incidence Surveillance Project conducted surveillance of patients with influenza-like illness (ILI). Respiratory specimens were collected from the first 10 ILI patients each week with demographic and clinical data. Specimens were tested for multiple respiratory viruses, including PIV1–4, using reverse transcriptase–polymerase chain reaction assays. Cumulative incidence was calculated using provider patient population size as the denominator. RESULTS: PIVs 1–3 were detected in 8.0% of 7716 ILI-related outpatient specimens: 30% were PIV1, 26% PIV2 and 44% PIV3. PIV circulation varied noticeably by year and type, with PIV3 predominating in 2010–2011 (incidence 110 per 100,000 children), PIV1 in 2011–2012 (89 per 100,000), dual predominance of PIV2 and PIV3 (88 and 131 per 100,000) in 2012–2013 and PIV3 (100 per 100,000) in 2013–2014. The highest incidence of PIV detections was among patients aged <5 years (259–1307 per 100,000). The median age at detection for PIV3 (3.4 years) was significantly lower than the median ages for PIV1 (4.5 years) and PIV2 (7.0 years; P < 0.05). CONCLUSIONS: PIVs 1–3 comprise a substantial amount of medically attended pediatric ILI, particularly among children aged <5 years. Distinct seasonal circulation patterns as well as significant differences in rates by age were observed between PIV types.",2016 Jul 28,"['Steffens, Andrea', 'Finelli, Lyn', 'Whitaker, Brett', 'Fowlkes, Ashley']",Pediatr Infect Dis J,,,True
8c96d28abcf7aa309ce804e40c11c9caf88a7a62,PMC,Patient and family satisfaction levels in the intensive care unit after elective cardiac surgery: study protocol for a randomised controlled trial of a preoperative patient education intervention,http://dx.doi.org/10.1136/bmjopen-2016-011341,PMC4932258,27334883,CC BY-NC,"INTRODUCTION: Patients and their families are understandably anxious about the risk of complications and unfamiliar experiences following cardiac surgery. Providing information about postoperative care in the intensive care unit (ICU) to patients and families may lead to lower anxiety levels, and increased satisfaction with healthcare. The objectives of this study are to evaluate the effectiveness of preoperative patient education provided for patients undergoing elective cardiac surgery. METHODS AND ANALYSIS: 100 patients undergoing elective coronary artery bypass graft, with or without valve replacement surgery, will be recruited into a 2-group, parallel, superiority, double-blinded randomised controlled trial. Participants will be randomised to either preoperative patient education comprising of a video and ICU tour with standard care (intervention) or standard education (control). The primary outcome measures are the satisfaction levels of patients and family members with ICU care and decision-making in the ICU. The secondary outcome measures are patient anxiety and depression levels before and after surgery. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Joint Chinese University of Hong Kong—New Territories East Cluster Clinical Research Ethics Committee (reference number CREC 2015.308). The findings will be presented at conferences and published in peer-reviewed journals. Study participants will receive a 1-page plain language summary of results. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-15006971.",2016 Jun 22,"['Lai, Veronica Ka Wai', 'Lee, Anna', 'Leung, Patricia', 'Chiu, Chun Hung', 'Ho, Ka Man', 'Gomersall, Charles David', 'Underwood, Malcolm John', 'Joynt, Gavin Matthew']",BMJ Open,,,True
818b42cf815357fc1ee73a17caa5dfef24c55027,PMC,"Stress, Nutrition, and Intestinal Immune Responses in Pigs — A Review",http://dx.doi.org/10.5713/ajas.16.0118,PMC4932560,27189643,CC BY-NC,"Modern livestock production became highly intensive and large scaled to increase production efficiency. This production environment could add stressors affecting the health and growth of animals. Major stressors can include environment (air quality and temperature), nutrition, and infection. These stressors can reduce growth performance and alter immune systems at systemic and local levels including the gastrointestinal tract. Heat stress increases the permeability, oxidative stress, and inflammatory responses in the gut. Nutritional stress from fasting, antinutritional compounds, and toxins induces the leakage and destruction of the tight junction proteins in the gut. Fasting is shown to suppress pro-inflammatory cytokines, whereas deoxynivalenol increases the recruitment of intestinal pro-inflammatory cytokines and the level of lymphocytes in the gut. Pathogenic and viral infections such as Enterotoxigenic E. coli (ETEC) and porcine epidemic diarrhea virus can lead to loosening the intestinal epithelial barrier. On the other hand, supplementation of Lactobacillus or Saccharaomyces reduced infectious stress by ETEC. It was noted that major stressors altered the permeability of intestinal barriers and profiles of genes and proteins of pro-inflammatory cytokines and chemokines in mucosal system in pigs. However, it is not sufficient to fully explain the mechanism of the gut immune system in pigs under stress conditions. Correlation and interaction of gut and systemic immune system under major stressors should be better defined to overcome aforementioned obstacles.",2016 Aug 12,"['Lee, In Kyu', 'Kye, Yoon Chul', 'Kim, Girak', 'Kim, Han Wool', 'Gu, Min Jeong', 'Umboh, Johnny', 'Maaruf, Kartini', 'Kim, Sung Woo', 'Yun, Cheol-Heui']",Asian-Australas J Anim Sci,,,True
58fe95f5d7af4547a90fd2a13f17ac10d89de75d,PMC,News,http://dx.doi.org/10.1183/20734735.news122,PMC4933631,,CC BY-NC,"There are just a few weeks left to get the early bird discount for registration at the ERS International Congress. This year's event, which will take place in London for the first time, provides a key opportunity to hear the latest research and advances from across the broad spectrum of the respiratory field.",2016 Jun,,Breathe (Sheff),,,False
bd667dbd5200c9f07fb07cef29435f7ca7c2639b,PMC,Establishment of serological test to detect antibody against ferret coronavirus,http://dx.doi.org/10.1292/jvms.16-0059,PMC4937135,26935842,CC BY-NC-ND,"Since there is no available serological methods to detect antibodies to ferret coronavirus (FRCoV), an enzyme-linked immunosorbent assay (ELISA) using recombinant partial nucleocapsid (N) proteins of the ferret coronavirus (FRCoV) Yamaguchi-1 strain was developed to establish a serological method for detection of FRCoV infection. Many serum samples collected from ferrets recognized both a.a. 1–179 and a.a. 180–374 of the N protein, but two serum samples did not a.a. 180–374 of the N protein. This different reactivity was also confirmed by immunoblot analysis using the serum from the ferret.Therefore, the a.a. 1–179 of the N protein was used as an ELISA antigen. Serological test was carried out using sera or plasma of ferrets in Japan. Surprisingly, 89% ferrets in Japan had been infected with FRCoV. These results indicated that our established ELISA using a.a. 1–179 of the N protein is useful for detection of antibody to FRCoV for diagnosis and seroepidemiology of FRCoV infection.",2016 Jun 3,"['MINAMI, Shohei', 'TERADA, Yutaka', 'SHIMODA, Hiroshi', 'TAKIZAWA, Masaki', 'ONUMA, Mamoru', 'OTA, Akihiko', 'OTA, Yuichi', 'AKABANE, Yoshihito', 'TAMUKAI, Kenichi', 'WATANABE, Keiichiro', 'NAGANUMA, Yumiko', 'KANAGAWA, Eiichi', 'NAKAMURA, Kaneichi', 'OHASHI, Masanari', 'TAKAMI, Yoshinori', 'MIWA, Yasutsugu', 'TANOUE, Tomoaki', 'OHWAKI, Masao', 'OHTA, Jouji', 'UNE, Yumi', 'MAEDA, Ken']",J Vet Med Sci,,,True
357fe51849c655d37552b3f96c67be8394a9b6e5,PMC,Analytical and Clinical Validation of Six Commercial Middle East Respiratory Syndrome Coronavirus RNA Detection Kits Based on Real-Time Reverse-Transcription PCR,http://dx.doi.org/10.3343/alm.2016.36.5.450,PMC4940488,27374710,CC BY-NC,"BACKGROUND: During the 2015 outbreak of Middle East Respiratory Syndrome coronavirus (MERS-CoV), six different commercial MERS-CoV RNA detection kits based on real-time reverse-transcription polymerase chain reaction (rRT-PCR) were available in Korea. We performed analytical and clinical validations of these kits. METHODS: PowerChek (Kogene Biotech, Korea), DiaPlexQ (SolGent, Korea), Anyplex (Seegene, Korea), AccuPower (Bioneer, Korea), LightMix (Roche Molecular Diagnostics, Switzerland), and UltraFast kits (Nanobiosys, Korea) were evaluated. Limits of detection (LOD) with 95% probability values were estimated by testing 16 replicates of upstream of the envelope gene (upE) and open reading frame 1a (ORF1a) RNA transcripts. Specificity was estimated by using 28 nasopharyngeal swabs that were positive for other respiratory viruses. Clinical sensitivity was evaluated by using 18 lower respiratory specimens. The sensitivity test panel and the high inhibition panel were composed of nine specimens each, including eight and six specimens that were positive for MERS-CoV, respectively. RESULTS: The LODs for upE ranged from 21.88 to 263.03 copies/reaction, and those for ORF1a ranged from 6.92 to 128.82 copies/reaction. No cross-reactivity with other respiratory viruses was found. All six kits correctly identified 8 of 8 (100%) positive clinical specimens. Based on results from the high inhibition panel, PowerChek and AccuPower were the least sensitive to the presence of PCR inhibition. CONCLUSIONS: The overall sensitivity and specificity of all six assay systems were sufficient for diagnosing MERS-CoV infection. However, the analytical sensitivity and detection ability in specimens with PCR inhibition could be improved with the use of appropriate internal controls.",2016 Sep 24,"['Kim, Mi-Na', 'Ko, Young Jin', 'Seong, Moon-Woo', 'Kim, Jae-Seok', 'Shin, Bo-Moon', 'Sung, Heungsup']",Ann Lab Med,,,True
01aa247284f0baf43293d8ea335b70781365a985,PMC,Comparative Evaluation of Three Homogenization Methods for Isolating Middle East Respiratory Syndrome Coronavirus Nucleic Acids From Sputum Samples for Real-Time Reverse Transcription PCR,http://dx.doi.org/10.3343/alm.2016.36.5.457,PMC4940489,27374711,CC BY-NC,"BACKGROUND: Real-time reverse transcription PCR (rRT-PCR) of sputum samples is commonly used to diagnose Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Owing to the difficulty of extracting RNA from sputum containing mucus, sputum homogenization is desirable prior to nucleic acid isolation. We determined optimal homogenization methods for isolating viral nucleic acids from sputum. METHODS: We evaluated the following three sputum-homogenization methods: proteinase K and DNase I (PK-DNase) treatment, phosphate-buffered saline (PBS) treatment, and N-acetyl-L-cysteine and sodium citrate (NALC) treatment. Sputum samples were spiked with inactivated MERS-CoV culture isolates. RNA was extracted from pretreated, spiked samples using the easyMAG system (bioMérieux, France). Extracted RNAs were then subjected to rRT-PCR for MERS-CoV diagnosis (DiaPlex Q MERS-coronavirus, SolGent, Korea). RESULTS: While analyzing 15 spiked sputum samples prepared in technical duplicate, false-negative results were obtained with five (16.7%) and four samples (13.3%), respectively, by using the PBS and NALC methods. The range of threshold cycle (Ct) values observed when detecting upE in sputum samples was 31.1–35.4 with the PK-DNase method, 34.7–39.0 with the PBS method, and 33.9–38.6 with the NALC method. Compared with the control, which were prepared by adding a one-tenth volume of 1:1,000 diluted viral culture to PBS solution, the ranges of Ct values obtained by the PBS and NALC methods differed significantly from the mean control Ct of 33.2 (both P<0.0001). CONCLUSIONS: The PK-DNase method is suitable for homogenizing sputum samples prior to RNA extraction.",2016 Sep 24,"['Sung, Heungsup', 'Yong, Dongeun', 'Ki, Chang-Seok', 'Kim, Jae-Seok', 'Seong, Moon-Woo', 'Lee, Hyukmin', 'Kim, Mi-Na']",Ann Lab Med,,,True
73f48a992c779f349ff5e305afe2f0538699ec33,PMC,Incidence of Medically Attended Respiratory Syncytial Virus and Influenza Illnesses in Children 6–59 Months Old During Four Seasons,http://dx.doi.org/10.1093/ofid/ofw081,PMC4943552,27419158,CC BY-NC-ND,"Background. Respiratory syncytial virus (RSV) and influenza are significant causes of seasonal respiratory illness in children. The incidence of influenza and RSV hospitalization is well documented, but the incidence of medically attended, laboratory-confirmed illness has not been assessed in a well defined community cohort. Methods. Children aged 6–59 months with medically attended acute respiratory illness were prospectively enrolled during the 2006–2007 through 2009–2010 influenza seasons in a Wisconsin community cohort. Nasal swabs were tested for RSV and influenza by multiplex reverse-transcription polymerase chain reaction. The population incidence of medically attended RSV and influenza was estimated separately and standardized to weeks 40 through 18 of each season. Results. The cohort included 2800–3073 children each season. There were 2384 children enrolled with acute respiratory illness; 627 (26%) were positive for RSV and 314 (13%) for influenza. The mean age was 28 months (standard deviation [SD] = 15) for RSV-positive and 38 months (SD = 16) for influenza-positive children. Seasonal incidence (cases per 10 000) was 1718 (95% confidence interval [CI], 1602–1843) for RSV and 768 (95% CI, 696–848) for influenza. Respiratory syncytial virus incidence was highest among children 6–11 (2927) and 12–23 months old (2377). Influenza incidence was highest (850) in children 24–59 months old. The incidence of RSV was higher than influenza across all seasons and age groups. Conclusions. The incidence of medically attended RSV was highest in children 6–23 months old, and it was consistently higher than influenza. The burden of RSV remains high throughout the first 2 years of life.",2016 Apr 21,"['Simpson, Melissa D.', 'Kieke, Burney A.', 'Sundaram, Maria E.', 'McClure, David L.', 'Meece, Jennifer K.', 'Sifakis, Frangiscos', 'Gasser, Robert A.', 'Belongia, Edward A.']",Open Forum Infect Dis,,,True
3d5f2ea9eca2aa8acb508626fef27e7b1c087312,PMC,"Clinical aspects of influenza A(H1N1)pdm09 cases reported during the pandemic in Brazil, 2009-2010",http://dx.doi.org/10.1590/S1679-45082015AO3331,PMC4943806,26154537,CC BY-NC,"OBJECTIVE: To describe the clinical aspects of cases of influenza A(H1N1)pdm09 in Brazil. METHODS: A descriptive study of cases reported in Sistema de Informação de Agravos de Notificação (SINAN), 2009-2010. RESULTS: As the final classification, we obtained 53,797 (56.79%) reported cases confirmed as a new influenza virus subtype, and 40,926 (43.21%) cases discarded. Fever was the most common sign, recorded in 99.74% of the confirmed and 98.92% of the discarded cases. Among the confirmed cases, the presence of comorbidities was reported in 32.53%, and in 38.29% of the discarded cases. The case fatality rate was 4.04%; 3,267 pregnant women were confirmed positive for influenza A new viral subtype and 2,730 of them were cured. The case fatality rate of pregnant women was 6.88%. CONCLUSION: The findings suggested concern of the health system with pregnant women, and patients with comorbidities and quality of care may have favored a lower mortality. We recommend that, when caring for patients with severe respiratory symptoms, with comorbidities, or pregnant women, health professionals should consider the need for hospital care, as these factors make up a worse prognosis of infection by the pandemic influenza virus.",2015 Apr-Jun,"['Rossetto, Érika Valeska', 'Luna, Expedito José de Albuquerque']",Einstein (Sao Paulo),,,True
3e43db4bbfa0307b42810ceb2b3cd07e2c321e2b,PMC,"Epidemiologic Parameters of the Middle East Respiratory Syndrome Outbreak in Korea, 2015",http://dx.doi.org/10.3947/ic.2016.48.2.108,PMC4945720,27433381,CC BY-NC,"BACKGROUND: Epidemiologic parameters are important in planning infection control policies during the outbreak of emerging infections. Korea experienced an outbreak of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection in 2015, which was characterized by superspreading events in healthcare settings. We aimed to estimate the epidemiologic parameters over time during the outbreak to assess the effectiveness of countermeasures. MATERIALS AND METHODS: Publicly available data pertaining to the MERS outbreak in Korea were collected. We estimated the incubation periods of 162 cases whose sources of exposure were identified and the temporal trend was evaluated. Factors influencing incubation duration were analyzed. The generational reproduction number (R(g)) and case reproduction number (R(c)) were estimated over time. RESULTS: The estimated median incubation period was 7.4 days (95% CI, 6.9-8.0). Median incubation periods tended to be longer over time as the disease generation progressed: 6.16 days (95% CI, 5.38-6.97), 7.68 days (95% CI, 7.04-8.44), and 7.95 days (95% CI, 6.25-9.88) in the first, second, and third generations, respectively. The number of days of illness in the source cases at the time of exposure inversely correlated with the incubation periods in the receiving cases (HR 0.91 [95% CI, 0.84-0.99] per one illness day increase; P=0.026). This relationship was consistent (HR 0.83 [95% CI, 0.74-0.93] per one illness day increase) in the multivariable analysis incorporating clinical characteristics, the order of generation, and a link to superspreaders. Because the third generation cases were exposed to their source cases in the early stage (median one day) compared to the second generation cases (median 6 days), the temporal trend of incubation periods appears to be influenced by early isolation of symptomatic cases and reduction of potential exposure to source cases in the later stage. R(g) declined rapidly from 28 to 0.23 in two generations. R(c) dropped below the epidemic threshold at one on May 31, 2015, which approximately coincided with the initiation of the stringent countermeasures. CONCLUSIONS: Despite the initial delay, the stringent countermeasures targeted towards second generation cases appeared to effectively contain the MERS outbreak in Korea as suggested by the decline of R(c) shortly after implementation. Except for superspreading events, the transmission potential for MERS-CoV seems to be low. Further research should be focused on characterizing superspreaders in comparison to non-transmitting cases with regard to environmental, behavioral, and virologic and host genetic factors in order to better prepare for future outbreaks of MERS-CoV.",2016 Jun 30,"['Park, Sun Hee', 'Kim, Woo Joo', 'Yoo, Jin-Hong', 'Choi, Jung-Hyun']",Infect Chemother,,,True
d6a37c3595d9abe648e28b0f54f35d0f533be9ea,PMC,"Epidemiologic Parameters of the Middle East Respiratory Syndrome Outbreak in Korea, 2015",http://dx.doi.org/10.3947/ic.2016.48.2.108,PMC4945720,27433381,CC BY-NC,"BACKGROUND: Epidemiologic parameters are important in planning infection control policies during the outbreak of emerging infections. Korea experienced an outbreak of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection in 2015, which was characterized by superspreading events in healthcare settings. We aimed to estimate the epidemiologic parameters over time during the outbreak to assess the effectiveness of countermeasures. MATERIALS AND METHODS: Publicly available data pertaining to the MERS outbreak in Korea were collected. We estimated the incubation periods of 162 cases whose sources of exposure were identified and the temporal trend was evaluated. Factors influencing incubation duration were analyzed. The generational reproduction number (R(g)) and case reproduction number (R(c)) were estimated over time. RESULTS: The estimated median incubation period was 7.4 days (95% CI, 6.9-8.0). Median incubation periods tended to be longer over time as the disease generation progressed: 6.16 days (95% CI, 5.38-6.97), 7.68 days (95% CI, 7.04-8.44), and 7.95 days (95% CI, 6.25-9.88) in the first, second, and third generations, respectively. The number of days of illness in the source cases at the time of exposure inversely correlated with the incubation periods in the receiving cases (HR 0.91 [95% CI, 0.84-0.99] per one illness day increase; P=0.026). This relationship was consistent (HR 0.83 [95% CI, 0.74-0.93] per one illness day increase) in the multivariable analysis incorporating clinical characteristics, the order of generation, and a link to superspreaders. Because the third generation cases were exposed to their source cases in the early stage (median one day) compared to the second generation cases (median 6 days), the temporal trend of incubation periods appears to be influenced by early isolation of symptomatic cases and reduction of potential exposure to source cases in the later stage. R(g) declined rapidly from 28 to 0.23 in two generations. R(c) dropped below the epidemic threshold at one on May 31, 2015, which approximately coincided with the initiation of the stringent countermeasures. CONCLUSIONS: Despite the initial delay, the stringent countermeasures targeted towards second generation cases appeared to effectively contain the MERS outbreak in Korea as suggested by the decline of R(c) shortly after implementation. Except for superspreading events, the transmission potential for MERS-CoV seems to be low. Further research should be focused on characterizing superspreaders in comparison to non-transmitting cases with regard to environmental, behavioral, and virologic and host genetic factors in order to better prepare for future outbreaks of MERS-CoV.",2016 Jun 30,"['Park, Sun Hee', 'Kim, Woo Joo', 'Yoo, Jin-Hong', 'Choi, Jung-Hyun']",Infect Chemother,,,False
1d8907508d6c233f454408abbfd624a9fda81f37,PMC,Clinical Presentation and Outcomes of Middle East Respiratory Syndrome in the Republic of Korea,http://dx.doi.org/10.3947/ic.2016.48.2.118,PMC4945721,27433382,CC BY-NC,"BACKGROUND: From May to July 2015, the Republic of Korea experienced the largest outbreak of Middle East respiratory syndrome (MERS) outside the Arabian Peninsula. A total of 186 patients, including 36 deaths, had been diagnosed with MERS-coronavirus (MERS-CoV) infection as of September 30th, 2015. MATERIALS AND METHODS: We obtained information of patients who were confirmed to have MERS-CoV infection. MERS-CoV infection was diagnosed using real-time reverse-transcriptase polymerase chain reaction assay. RESULTS: The median age of the patients was 55 years (range, 16 to 86). A total of 55.4% of the patients had one or more coexisting medical conditions. The most common symptom was fever (95.2%). At admission, leukopenia (42.6%), thrombocytopenia (46.6%), and elevation of aspartate aminotransferase (42.7%) were observed. Pneumonia was detected in 68.3% of patients at admission and developed in 80.8% during the disease course. Antiviral agents were used for 74.7% of patients. Mechanical ventilation, extracorporeal membrane oxygenation, and convalescent serum were employed for 24.5%, 7.1%, and 3.8% of patients, respectively. Older age, presence of coexisting medical conditions including diabetes or chronic lung disease, presence of dyspnea, hypotension, and leukocytosis at admission, and the use of mechanical ventilation were revealed to be independent predictors of death. CONCLUSION: The clinical features of MERS-CoV infection in the Republic of Korea were similar to those of previous outbreaks in the Middle East. However, the overall mortality rate (20.4%) was lower than that in previous reports. Enhanced surveillance and active management of patients during the outbreak may have resulted in improved outcomes.",2016 Jun 30,"['Choi, Won Suk', 'Kang, Cheol-In', 'Kim, Yonjae', 'Choi, Jae-Phil', 'Joh, Joon Sung', 'Shin, Hyoung-Shik', 'Kim, Gayeon', 'Peck, Kyong Ran', 'Chung, Doo Ryeon', 'Kim, Hye Ok', 'Song, Sook Hee', 'Kim, Yang Ree', 'Sohn, Kyung Mok', 'Jung, Younghee', 'Bang, Ji Hwan', 'Kim, Nam Joong', 'Lee, Kkot Sil', 'Jeong, Hye Won', 'Rhee, Ji-Young', 'Kim, Eu Suk', 'Woo, Heungjeong', 'Oh, Won Sup', 'Huh, Kyungmin', 'Lee, Young Hyun', 'Song, Joon Young', 'Lee, Jacob', 'Lee, Chang-Seop', 'Kim, Baek-Nam', 'Choi, Young Hwa', 'Jeong, Su Jin', 'Lee, Jin-Soo', 'Yoon, Ji Hyun', 'Wi, Yu Mi', 'Joung, Mi Kyong', 'Park, Seong Yeon', 'Lee, Sun Hee', 'Jung, Sook-In', 'Kim, Shin-Woo', 'Lee, Jae Hoon', 'Lee, Hyuck', 'Ki, Hyun Kyun', 'Kim, Yeon-Sook', None]",Infect Chemother,,,True
3ca41eba26adc5422815f1d8043e76b406e747bd,PMC,The Korean Middle East Respiratory Syndrome Coronavirus Outbreak and Our Responsibility to the Global Scientific Community,http://dx.doi.org/10.3947/ic.2016.48.2.145,PMC4945727,27433388,CC BY-NC,,2016 Jun 30,"Oh, Myoung-don",Infect Chemother,,,True
b08ae4f14b481f3eaa815fce88861d695fafeeb8,PMC,Understanding and Modeling the Super-spreading Events of the Middle East Respiratory Syndrome Outbreak in Korea,http://dx.doi.org/10.3947/ic.2016.48.2.147,PMC4945728,27433389,CC BY-NC,,2016 Jun 30,"Chun, Byung Chul",Infect Chemother,,,True
954d000b2e7252ffb05812341a6436d3d784494a,PMC,Collaborative Intervention of Middle East Respiratory Syndrome: Rapid Response Team,http://dx.doi.org/10.3947/ic.2016.48.2.71,PMC4945729,27433376,CC BY-NC,"On May 20th 2015, a 68 year old man was the first to be diagnosed with Middle East Respiratory Syndrome-Corona Virus (MERS-CoV) in Korea. He travelled to Bahrain, Saudi Arabia, and Qatar for 16 days. On May 4th 2015, the patient entered Korea, with febrile sense and respiratory symptoms that appeared on May 11th. The MERS-CoV Outbreak became worse and several patients had to be admitted throughout various hospitals starting at the beginning of June. This situation led to a nationwide chaos. The Rapid Response Team (RRT) was organized after the Korean government's calling for specialists that were composed of 15 Infectious disease Doctors and 2 Infection Control professionals on the 8th of June 2015. The main purpose of the RRT were: 1) consultation to the Government controlling MERS-CoV outbreak. 2) Visit hospitals that were exposed to MERS-CoV infected patients, and to provide advice regarding infection control strategy for rehabilitating of the exposed hospitals. Since June 8th, the RRT visited more than 10 hospitals and an effective consultation was carried out. Most of the hospitals were recovering from the MERS outbreak since early July. Cooperation between the government and private sector experts was very effective. The efforts of government and private sector experts overcame the initial chaos situation. It could prevent further deterioration of the MERS outbreak.",2016 Jun 30,"['Lee, Jacob', None, 'Kim, Woo Joo']",Infect Chemother,,,True
7a11ebc3954fa5d2d95ad487b8540bc73feb68f1,PMC,Institutional Preparedness to Prevent Future Middle East Respiratory Syndrome Coronavirus-Like Outbreaks in Republic of Korea,http://dx.doi.org/10.3947/ic.2016.48.2.75,PMC4945730,27433377,CC BY-NC,"A year has passed since the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea. This 2015 outbreak led to a better understanding of healthcare infection control. The first Korean patient infected by Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was diagnosed on May 20, 2015, after he returned from Qatar and Bahrain. Thereafter, 186 Korean people were infected with the MERS-CoV in a short time through human-to-human transmission. All these cases were linked to healthcare settings, and 25 (13.5 %) infected patients were healthcare workers. Phylogenetic analysis suggested that the MERS-CoV isolate found in the Korean patient was closely related to the Qatar strain, and did not harbor transmission efficiency-improving mutations. Nevertheless, with the same infecting virus strain, Korea experienced the largest MERS-CoV outbreak outside the Arabian Peninsula, primarily due to the different characteristics of population density and the healthcare system. We aimed to review the epidemiological features and existing knowledge on the Korean MERS outbreak, and suggest methods to prevent future epidemics.",2016 Jun 30,"['Jeon, Min Huok', 'Kim, Tae Hyong']",Infect Chemother,,,True
065497953c64b5163eb29e9a4fe78534f244ca26,PMC,"Outbreaks of Middle East Respiratory Syndrome in Two Hospitals Initiated by a Single Patient in Daejeon, South Korea",http://dx.doi.org/10.3947/ic.2016.48.2.99,PMC4945733,27433380,CC BY-NC,"BACKGROUND: A Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 started by a single imported case and was amplified by intra- and inter-hospital transmission. We describe two hospital outbreaks of MERS-CoV infection in Daejeon caused by a single patient who was infected by the first Korean case of MERS. MATERIALS AND METHODS: Demographic and clinical information involving MERS cases in the Daejeon cluster were retrospectively collected and potential contacts and exposures were assessed. The incubation periods and serial intervals were estimated. Viral RNAs were extracted from respiratory tract samples obtained from the index case, four secondary cases and one tertiary case from each hospital. The partial S2 domain of the MERS-CoV spike was sequenced. RESULTS: In Daejeon, a MERS patient (the index case) was hospitalized at Hospital A in the first week of illness and was transferred to Hospital B because of pneumonia progression in the second week of illness, where he received a bronchoscopic examination and nebulizer therapy. A total of 23 secondary cases (10 in Hospital A and 13 in Hospital B) were detected among patients and caregivers who stayed on the same ward with the index case. There were no secondary cases among healthcare workers. Among close hospital contacts, the secondary attack rate was 15.8% (12/76) in Hospital A and 14.3% (10/70) in Hospital B. However, considering the exposure duration, the incidence rate was higher in Hospital B (7.7/100 exposure-days) than Hospital A (3.4/100 exposure-days). In Hospital B, the median incubation period was shorter (4.6 days vs. 10.8 days), the median time to pneumonia development was faster (3 days vs. 6 days) and mortality was higher (70% vs. 30.8%) than in Hospital A. MERS-CoV isolates from 11 cases formed a single monophyletic clade, with the closest similarity to strains from Riyadh. CONCLUSION: Exposure to the MERS case in the late stage (2nd week) of diseases appeared to increase the risk of transmission and was associated with shorter incubation periods and rapid disease progression among those infected. Early detection and isolation of cases is critical in preventing the spread of MERS in the hospital and decreasing the disease severity among those infected.",2016 Jun 30,"['Park, Sun Hee', 'Kim, Yeon-Sook', 'Jung, Younghee', 'Choi, Soo young', 'Cho, Nam-Hyuk', 'Jeong, Hye Won', 'Heo, Jung Yeon', 'Yoon, Ji Hyun', 'Lee, Jacob', 'Cheon, Shinhye', 'Sohn, Kyung Mok']",Infect Chemother,,,True
e65003ed8edee134b33e89d81509e4d504d32217,PMC,"Outbreaks of Middle East Respiratory Syndrome in Two Hospitals Initiated by a Single Patient in Daejeon, South Korea",http://dx.doi.org/10.3947/ic.2016.48.2.99,PMC4945733,27433380,CC BY-NC,"BACKGROUND: A Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 started by a single imported case and was amplified by intra- and inter-hospital transmission. We describe two hospital outbreaks of MERS-CoV infection in Daejeon caused by a single patient who was infected by the first Korean case of MERS. MATERIALS AND METHODS: Demographic and clinical information involving MERS cases in the Daejeon cluster were retrospectively collected and potential contacts and exposures were assessed. The incubation periods and serial intervals were estimated. Viral RNAs were extracted from respiratory tract samples obtained from the index case, four secondary cases and one tertiary case from each hospital. The partial S2 domain of the MERS-CoV spike was sequenced. RESULTS: In Daejeon, a MERS patient (the index case) was hospitalized at Hospital A in the first week of illness and was transferred to Hospital B because of pneumonia progression in the second week of illness, where he received a bronchoscopic examination and nebulizer therapy. A total of 23 secondary cases (10 in Hospital A and 13 in Hospital B) were detected among patients and caregivers who stayed on the same ward with the index case. There were no secondary cases among healthcare workers. Among close hospital contacts, the secondary attack rate was 15.8% (12/76) in Hospital A and 14.3% (10/70) in Hospital B. However, considering the exposure duration, the incidence rate was higher in Hospital B (7.7/100 exposure-days) than Hospital A (3.4/100 exposure-days). In Hospital B, the median incubation period was shorter (4.6 days vs. 10.8 days), the median time to pneumonia development was faster (3 days vs. 6 days) and mortality was higher (70% vs. 30.8%) than in Hospital A. MERS-CoV isolates from 11 cases formed a single monophyletic clade, with the closest similarity to strains from Riyadh. CONCLUSION: Exposure to the MERS case in the late stage (2nd week) of diseases appeared to increase the risk of transmission and was associated with shorter incubation periods and rapid disease progression among those infected. Early detection and isolation of cases is critical in preventing the spread of MERS in the hospital and decreasing the disease severity among those infected.",2016 Jun 30,"['Park, Sun Hee', 'Kim, Yeon-Sook', 'Jung, Younghee', 'Choi, Soo young', 'Cho, Nam-Hyuk', 'Jeong, Hye Won', 'Heo, Jung Yeon', 'Yoon, Ji Hyun', 'Lee, Jacob', 'Cheon, Shinhye', 'Sohn, Kyung Mok']",Infect Chemother,,,False
62fa2e1a12e96812f655449d80dfc4f62483c5f3,PMC,"Outbreaks of Middle East Respiratory Syndrome in Two Hospitals Initiated by a Single Patient in Daejeon, South Korea",http://dx.doi.org/10.3947/ic.2016.48.2.99,PMC4945733,27433380,CC BY-NC,"BACKGROUND: A Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 started by a single imported case and was amplified by intra- and inter-hospital transmission. We describe two hospital outbreaks of MERS-CoV infection in Daejeon caused by a single patient who was infected by the first Korean case of MERS. MATERIALS AND METHODS: Demographic and clinical information involving MERS cases in the Daejeon cluster were retrospectively collected and potential contacts and exposures were assessed. The incubation periods and serial intervals were estimated. Viral RNAs were extracted from respiratory tract samples obtained from the index case, four secondary cases and one tertiary case from each hospital. The partial S2 domain of the MERS-CoV spike was sequenced. RESULTS: In Daejeon, a MERS patient (the index case) was hospitalized at Hospital A in the first week of illness and was transferred to Hospital B because of pneumonia progression in the second week of illness, where he received a bronchoscopic examination and nebulizer therapy. A total of 23 secondary cases (10 in Hospital A and 13 in Hospital B) were detected among patients and caregivers who stayed on the same ward with the index case. There were no secondary cases among healthcare workers. Among close hospital contacts, the secondary attack rate was 15.8% (12/76) in Hospital A and 14.3% (10/70) in Hospital B. However, considering the exposure duration, the incidence rate was higher in Hospital B (7.7/100 exposure-days) than Hospital A (3.4/100 exposure-days). In Hospital B, the median incubation period was shorter (4.6 days vs. 10.8 days), the median time to pneumonia development was faster (3 days vs. 6 days) and mortality was higher (70% vs. 30.8%) than in Hospital A. MERS-CoV isolates from 11 cases formed a single monophyletic clade, with the closest similarity to strains from Riyadh. CONCLUSION: Exposure to the MERS case in the late stage (2nd week) of diseases appeared to increase the risk of transmission and was associated with shorter incubation periods and rapid disease progression among those infected. Early detection and isolation of cases is critical in preventing the spread of MERS in the hospital and decreasing the disease severity among those infected.",2016 Jun 30,"['Park, Sun Hee', 'Kim, Yeon-Sook', 'Jung, Younghee', 'Choi, Soo young', 'Cho, Nam-Hyuk', 'Jeong, Hye Won', 'Heo, Jung Yeon', 'Yoon, Ji Hyun', 'Lee, Jacob', 'Cheon, Shinhye', 'Sohn, Kyung Mok']",Infect Chemother,,,False
a689c43a0741da0c152aba6ebb7e706fa6f3768f,PMC,"Outbreaks of Middle East Respiratory Syndrome in Two Hospitals Initiated by a Single Patient in Daejeon, South Korea",http://dx.doi.org/10.3947/ic.2016.48.2.99,PMC4945733,27433380,CC BY-NC,"BACKGROUND: A Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 started by a single imported case and was amplified by intra- and inter-hospital transmission. We describe two hospital outbreaks of MERS-CoV infection in Daejeon caused by a single patient who was infected by the first Korean case of MERS. MATERIALS AND METHODS: Demographic and clinical information involving MERS cases in the Daejeon cluster were retrospectively collected and potential contacts and exposures were assessed. The incubation periods and serial intervals were estimated. Viral RNAs were extracted from respiratory tract samples obtained from the index case, four secondary cases and one tertiary case from each hospital. The partial S2 domain of the MERS-CoV spike was sequenced. RESULTS: In Daejeon, a MERS patient (the index case) was hospitalized at Hospital A in the first week of illness and was transferred to Hospital B because of pneumonia progression in the second week of illness, where he received a bronchoscopic examination and nebulizer therapy. A total of 23 secondary cases (10 in Hospital A and 13 in Hospital B) were detected among patients and caregivers who stayed on the same ward with the index case. There were no secondary cases among healthcare workers. Among close hospital contacts, the secondary attack rate was 15.8% (12/76) in Hospital A and 14.3% (10/70) in Hospital B. However, considering the exposure duration, the incidence rate was higher in Hospital B (7.7/100 exposure-days) than Hospital A (3.4/100 exposure-days). In Hospital B, the median incubation period was shorter (4.6 days vs. 10.8 days), the median time to pneumonia development was faster (3 days vs. 6 days) and mortality was higher (70% vs. 30.8%) than in Hospital A. MERS-CoV isolates from 11 cases formed a single monophyletic clade, with the closest similarity to strains from Riyadh. CONCLUSION: Exposure to the MERS case in the late stage (2nd week) of diseases appeared to increase the risk of transmission and was associated with shorter incubation periods and rapid disease progression among those infected. Early detection and isolation of cases is critical in preventing the spread of MERS in the hospital and decreasing the disease severity among those infected.",2016 Jun 30,"['Park, Sun Hee', 'Kim, Yeon-Sook', 'Jung, Younghee', 'Choi, Soo young', 'Cho, Nam-Hyuk', 'Jeong, Hye Won', 'Heo, Jung Yeon', 'Yoon, Ji Hyun', 'Lee, Jacob', 'Cheon, Shinhye', 'Sohn, Kyung Mok']",Infect Chemother,,,False
cef66150e4522a400debfb51b33b3c03bf5e4e5d,PMC,"Outbreaks of Middle East Respiratory Syndrome in Two Hospitals Initiated by a Single Patient in Daejeon, South Korea",http://dx.doi.org/10.3947/ic.2016.48.2.99,PMC4945733,27433380,CC BY-NC,"BACKGROUND: A Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 started by a single imported case and was amplified by intra- and inter-hospital transmission. We describe two hospital outbreaks of MERS-CoV infection in Daejeon caused by a single patient who was infected by the first Korean case of MERS. MATERIALS AND METHODS: Demographic and clinical information involving MERS cases in the Daejeon cluster were retrospectively collected and potential contacts and exposures were assessed. The incubation periods and serial intervals were estimated. Viral RNAs were extracted from respiratory tract samples obtained from the index case, four secondary cases and one tertiary case from each hospital. The partial S2 domain of the MERS-CoV spike was sequenced. RESULTS: In Daejeon, a MERS patient (the index case) was hospitalized at Hospital A in the first week of illness and was transferred to Hospital B because of pneumonia progression in the second week of illness, where he received a bronchoscopic examination and nebulizer therapy. A total of 23 secondary cases (10 in Hospital A and 13 in Hospital B) were detected among patients and caregivers who stayed on the same ward with the index case. There were no secondary cases among healthcare workers. Among close hospital contacts, the secondary attack rate was 15.8% (12/76) in Hospital A and 14.3% (10/70) in Hospital B. However, considering the exposure duration, the incidence rate was higher in Hospital B (7.7/100 exposure-days) than Hospital A (3.4/100 exposure-days). In Hospital B, the median incubation period was shorter (4.6 days vs. 10.8 days), the median time to pneumonia development was faster (3 days vs. 6 days) and mortality was higher (70% vs. 30.8%) than in Hospital A. MERS-CoV isolates from 11 cases formed a single monophyletic clade, with the closest similarity to strains from Riyadh. CONCLUSION: Exposure to the MERS case in the late stage (2nd week) of diseases appeared to increase the risk of transmission and was associated with shorter incubation periods and rapid disease progression among those infected. Early detection and isolation of cases is critical in preventing the spread of MERS in the hospital and decreasing the disease severity among those infected.",2016 Jun 30,"['Park, Sun Hee', 'Kim, Yeon-Sook', 'Jung, Younghee', 'Choi, Soo young', 'Cho, Nam-Hyuk', 'Jeong, Hye Won', 'Heo, Jung Yeon', 'Yoon, Ji Hyun', 'Lee, Jacob', 'Cheon, Shinhye', 'Sohn, Kyung Mok']",Infect Chemother,,,False
14c76262143132d62e75952b54a92d8a7e29f2a9,PMC,Persistent Environmental Contamination and Prolonged Viral Shedding in MERS Patients During MERS-CoV Outbreak in South Korea,http://dx.doi.org/10.1093/ofid/ofv130.11,PMC4946541,,CC BY-NC-ND,,2015 Dec 9,"['Jeong, Hye Won', 'Heo, Jung Yeon', 'Kim, Hyung-Woo', 'Choi, Young Ki', 'Song, Min-Sok', 'Bin Seo, Yu', 'Lee, Jacob']",Open Forum Infect Dis,,,False
9ee72a92dba63a2f7ba385612fa69e180dc8ab09,PMC,Ebola Virus Disease Epidemic: What Can the World Learn and Not Learn from West Africa?,,PMC4948166,27621980,CC BY-NC-SA,"With over 4,500 deaths and counting, and new cases identified in two developed countries that are struggling and faltering in their handling of the epidemic, the 2014 Ebola Virus Disease (EVD) epidemic is unlike any of its kind ever encountered. The ability of some poor, resource-limited, developing countries in sub-Saharan Africa to efficiently handle the epidemic within their shores provides some lessons learned for the global health community. Among others, the 2014 EVD epidemic teaches us that it is time to put the “P” back in public and population health around the world. The global health community must support a sustainable strategy to mitigate Ebola virus and other epidemics both within and outside their shores, even after the cameras are gone. Ebola virus must not be called the disease of the poor and developing world.",2015,"['Azuine, Romuladus E.', 'Ekejiuba, Sussan E.', 'Singh, Gopal K.', 'Azuine, Magnus A.']",Int J MCH AIDS,,,True
4f7e3be54c93d119c3a1ddb753aa5394878a2bbe,PMC,Avoiding student infection during a Middle East respiratory syndrome (MERS) outbreak: a single medical school experience,http://dx.doi.org/10.3946/kjme.2016.30,PMC4951746,27240893,CC BY-NC,"PURPOSE: In outbreaks of infectious disease, medical students are easily overlooked in the management of healthcare personnel protection although they serve in clinical clerkships in hospitals. In the early summer of 2015, Middle East respiratory syndrome (MERS) struck South Korea, and students of Sungkyunkwan University School of Medicine (SKKUSOM) were at risk of contracting the disease. The purpose of this report is to share SKKUSOM’s experience against the MERS outbreak and provide suggestions for medical schools to consider in the face of similar challenges. METHODS: Through a process of reflection-on-action, we examined SKKUSOM’s efforts to avoid student infection during the MERS outbreak and derived a few practical guidelines that medical schools can adopt to ensure student safety in outbreaks of infectious disease. RESULTS: The school leadership conducted ongoing risk assessment and developed contingency plans to balance student safety and continuity in medical education. They rearranged the clerkships to another hospital and offered distant lectures and tutorials. Five suggestions are extracted for medical schools to consider in infection outbreaks: instant cessation of clinical clerkships; rational decision making on a school closure; use of information technology; constant communication with hospitals; and open communication with faculty, staff, and students. CONCLUSION: Medical schools need to take the initiative and actively seek countermeasures against student infection. It is essential that medical schools keep constant communication with their index hospitals and the involved personnel. In order to assure student learning, medical schools may consider offering distant education with online technology.",2016 Jun 27,"['Park, Seung Won', 'Jang, Hye Won', 'Choe, Yon Ho', 'Lee, Kyung Soo', 'Ahn, Yong Chan', 'Chung, Myung Jin', 'Lee, Kyu-Sung', 'Lee, Kyunghoon', 'Han, Taehee']",Korean J Med Educ,,,True
ecbdaacec058ed09ad1fc9b930fdb70e77b62f19,PMC,The Domestic Ferret (Mustela putorius furo) as a Lethal Infection Model for 3 Species of Ebolavirus,http://dx.doi.org/10.1093/infdis/jiw209,PMC4957446,27354371,CC BY-NC-ND,"Small-animal models have been developed for several Filoviridae species; however, serial adaptation was required to produce lethal infection. These adapted viruses have sequence changes in several genes, including those that modulate the host immune response. Nonhuman primate models do not require adaptation of filoviruses. Here, we describe lethal models of disease for Bundibugyo, Sudan, and Zaire species of Ebolavirus in the domestic ferret, using wild-type nonadapted viruses. Pathologic features were consistent with disease in primates. Of particular importance, this is the only known small-animal model developed for Bundibugyo and the only uniformly lethal animal model for Bundibugyo.",2016 Aug 15,"['Cross, Robert W.', 'Mire, Chad E.', 'Borisevich, Viktoriya', 'Geisbert, Joan B.', 'Fenton, Karla A.', 'Geisbert, Thomas W.']",J Infect Dis,,,True
be4f7c9109a242bfea7c73dbb551238cf598e690,PMC,Biosafety considerations for attenuated measles virus vectors used in virotherapy and vaccination,http://dx.doi.org/10.1080/21645515.2015.1122146,PMC4963060,26631840,CC BY-NC,"Attenuated measles virus (MV) is one of the most effective and safe vaccines available, making it attractive candidate vector to prevent infectious diseases. Attenuated MV have acquired the ability to use the complement regulator CD46 as a major receptor to mediate virus entry and intercellular fusion. Therefore, attenuated MV strains preferentially infect and destroy a wide variety of cancer cells making them also attractive oncolytic vectors. The use of recombinant MV vector has to comply with various regulatory requirements, particularly relating to the assessment of potential risks for human health and the environment. The present article highlights the main characteristics of MV and recombinant MV vectors used for vaccination and virotherapy and discusses these features from a biosafety point of view.",2015 Dec 2,"['Baldo, Aline', 'Galanis, Evanthia', 'Tangy, Frédéric', 'Herman, Philippe']",Hum Vaccin Immunother,,,True
ae665e8da5fde86d27ddfb4b31851550c5db92be,PMC,"Time to abandon the hygiene hypothesis: new perspectives on allergic disease, the human microbiome, infectious disease prevention and the role of targeted hygiene",http://dx.doi.org/10.1177/1757913916650225,PMC4966430,27354505,CC BY-NC,"AIMS: To review the burden of allergic and infectious diseases and the evidence for a link to microbial exposure, the human microbiome and immune system, and to assess whether we could develop lifestyles which reconnect us with exposures which could reduce the risk of allergic disease while also protecting against infectious disease. METHODS: Using methodology based on the Delphi technique, six experts in infectious and allergic disease were surveyed to allow for elicitation of group judgement and consensus view on issues pertinent to the aim. RESULTS: Key themes emerged where evidence shows that interaction with microbes that inhabit the natural environment and human microbiome plays an essential role in immune regulation. Changes in lifestyle and environmental exposure, rapid urbanisation, altered diet and antibiotic use have had profound effects on the human microbiome, leading to failure of immunotolerance and increased risk of allergic disease. Although evidence supports the concept of immune regulation driven by microbe–host interactions, the term ‘hygiene hypothesis’ is a misleading misnomer. There is no good evidence that hygiene, as the public understands, is responsible for the clinically relevant changes to microbial exposures. CONCLUSION: Evidence suggests a combination of strategies, including natural childbirth, breast feeding, increased social exposure through sport, other outdoor activities, less time spent indoors, diet and appropriate antibiotic use, may help restore the microbiome and perhaps reduce risks of allergic disease. Preventive efforts must focus on early life. The term ‘hygiene hypothesis’ must be abandoned. Promotion of a risk assessment approach (targeted hygiene) provides a framework for maximising protection against pathogen exposure while allowing spread of essential microbes between family members. To build on these findings, we must change public, public health and professional perceptions about the microbiome and about hygiene. We need to restore public understanding of hygiene as a means to prevent infectious disease.",2016 Jul 27,"['Bloomfield, Sally F', 'Rook, Graham AW', 'Scott, Elizabeth A', 'Shanahan, Fergus', 'Stanwell-Smith, Rosalind', 'Turner, Paul']",Perspect Public Health,,,True
6578e41e60b38d235bd575fb899804460ba1d4eb,PMC,Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes,http://dx.doi.org/10.1016/j.cell.2016.05.073,PMC4967455,27453466,CC BY-NC-ND,"Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir. Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross-reactive antibodies. The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans.",2016 Jul 28,"['Kallewaard, Nicole\xa0L.', 'Corti, Davide', 'Collins, Patrick\xa0J.', 'Neu, Ursula', 'McAuliffe, Josephine\xa0M.', 'Benjamin, Ebony', 'Wachter-Rosati, Leslie', 'Palmer-Hill, Frances\xa0J.', 'Yuan, Andy\xa0Q.', 'Walker, Philip\xa0A.', 'Vorlaender, Matthias\xa0K.', 'Bianchi, Siro', 'Guarino, Barbara', 'De\xa0Marco, Anna', 'Vanzetta, Fabrizia', 'Agatic, Gloria', 'Foglierini, Mathilde', 'Pinna, Debora', 'Fernandez-Rodriguez, Blanca', 'Fruehwirth, Alexander', 'Silacci, Chiara', 'Ogrodowicz, Roksana\xa0W.', 'Martin, Stephen\xa0R.', 'Sallusto, Federica', 'Suzich, JoAnn\xa0A.', 'Lanzavecchia, Antonio', 'Zhu, Qing', 'Gamblin, Steven\xa0J.', 'Skehel, John\xa0J.']",Cell,,,False
c0994f9da78269cb00a6b2af89b75ceba6f6c90d,PMC,Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes,http://dx.doi.org/10.1016/j.cell.2016.05.073,PMC4967455,27453466,CC BY-NC-ND,"Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir. Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross-reactive antibodies. The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans.",2016 Jul 28,"['Kallewaard, Nicole\xa0L.', 'Corti, Davide', 'Collins, Patrick\xa0J.', 'Neu, Ursula', 'McAuliffe, Josephine\xa0M.', 'Benjamin, Ebony', 'Wachter-Rosati, Leslie', 'Palmer-Hill, Frances\xa0J.', 'Yuan, Andy\xa0Q.', 'Walker, Philip\xa0A.', 'Vorlaender, Matthias\xa0K.', 'Bianchi, Siro', 'Guarino, Barbara', 'De\xa0Marco, Anna', 'Vanzetta, Fabrizia', 'Agatic, Gloria', 'Foglierini, Mathilde', 'Pinna, Debora', 'Fernandez-Rodriguez, Blanca', 'Fruehwirth, Alexander', 'Silacci, Chiara', 'Ogrodowicz, Roksana\xa0W.', 'Martin, Stephen\xa0R.', 'Sallusto, Federica', 'Suzich, JoAnn\xa0A.', 'Lanzavecchia, Antonio', 'Zhu, Qing', 'Gamblin, Steven\xa0J.', 'Skehel, John\xa0J.']",Cell,,,False
defb3d3bd1f210f27426c5f20d48c398f6600587,PMC,Modeling the hospital safety partnership preferences of patients and their families: a discrete choice conjoint experiment,http://dx.doi.org/10.2147/PPA.S105605,PMC4968982,27555752,CC BY-NC,"BACKGROUND: Patients and their families play an important role in efforts to improve health service safety. OBJECTIVE: The objective of this study is to understand the safety partnership preferences of patients and their families. METHOD: We used a discrete choice conjoint experiment to model the safety partnership preferences of 1,084 patients or those such as parents acting on their behalf. Participants made choices between hypothetical safety partnerships composed by experimentally varying 15 four-level partnership design attributes. RESULTS: Participants preferred an approach to safety based on partnerships between patients and staff rather than a model delegating responsibility for safety to hospital staff. They valued the opportunity to participate in point of service safety partnerships, such as identity and medication double checks, that might afford an immediate risk reduction. Latent class analysis yielded two segments. Actively engaged participants (73.3%) comprised outpatients with higher education, who anticipated more benefits to safety partnerships, were more confident in their ability to contribute, and were more intent on participating. They were more likely to prefer a personal engagement strategy, valued scientific evidence, preferred a more active approach to safety education, and advocated disclosure of errors. The passively engaged segment (26.7%) anticipated fewer benefits, were less confident in their ability to contribute, and were less intent on participating. They were more likely to prefer an engagement strategy based on signage. They preferred that staff explain why they thought patients should help make care safer and decide whether errors were disclosed. Inpatients, those with immigrant backgrounds, and those with less education were more likely to be in this segment. CONCLUSION: Health services need to communicate information regarding risks, ask about partnership preferences, create opportunities respecting individual differences, and ensure a positive response when patients raise safety concerns.",2016 Jul 26,"['Cunningham, Charles E', 'Hutchings, Tracy', 'Henderson, Jennifer', 'Rimas, Heather', 'Chen, Yvonne']",Patient Prefer Adherence,,,True
1f7f3e09db31be0bc73e921a1034ec9de0d52ebe,PMC,Miniaturization for Point-of-Care Analysis: Platform Technology for Almost Every Biomedical Assay,,PMC4975254,27683418,CC BY-NC,"Platform technologies for the changing need of diagnostics are one of the main challenges in medical device technology. From one point-of-view the demand for new and more versatile diagnostic is increasing due to a deeper knowledge of biomarkers and their combination with diseases. From another point-of-view a decentralization of diagnostics will occur since decisions can be made faster resulting in higher success of therapy. Hence, new types of technologies have to be established which enables a multiparameter analysis at the point-of-care. Within this review-like article a system called Fraunhofer ivD-platform is introduced. It consists of a credit-card sized cartridge with integrated reagents, sensors and pumps and a read-out/processing unit. Within the cartridge the assay runs fully automated within 15-20 minutes. Due to the open design of the platform different analyses such as antibody, serological or DNA-assays can be performed. Specific examples of these three different assay types are given to show the broad applicability of the system.",2012 Oct 12,"['Schumacher, Soeren', 'Sartorius, Dorian', 'Ehrentreich-Förster, Eva', 'Bier, Frank F.']",EJIFCC,,,True
7e54f67d82b8e54609d3029b20d765865895928d,PMC,Lung Cancer with Diffuse Ground-glass Shadow in Two Lungs and Respiratory Failure,http://dx.doi.org/10.4103/0366-6999.186632,PMC4976580,27453241,CC BY-NC-SA,,2016 Aug 5,"['Feng, Zhe-Min', 'Zhuang, Zhen-Jie', 'He, Wen-Bo', 'Ding, Jian-Ping', 'Yang, Wen-Jun', 'Chen, Xue-Yuan']",Chin Med J (Engl),,,True
2d5eaeaa1aa523394ce7697d3cbe98381a2c1559,PMC,Interferon Regulatory Factor-1 Mediates Alveolar Macrophage Pyroptosis During LPS-Induced Acute Lung Injury in Mice,http://dx.doi.org/10.1097/SHK.0000000000000595,PMC4978602,26939040,CC BY-NC-ND,"Previously, we demonstrated that pyroptosis in alveolar macrophages (AMs) plays an essential role in lipopolysaccharide (LPS)-induced acute lung injury. However, the underlying mechanism remains largely unclear. Here, we show that the absence of interferon regulatory factor 1 (IRF-1) in genetic knock-out mice strongly abrogates pyroptosis in AMs and alleviates the LPS-induced lung injury and systemic inflammation. Our study demonstrates that IRF-1 contributes to caspase-1 activation and apoptosis-associated speck-like protein containing a caspase activation and recruitment domain pyroptosome formation in AMs and leads to downstream inflammatory cytokine release, including that of IL-1β, IL-18, and HMGB1. The nuclear translocation of IRF-1 is linked to the presence of toll-like receptor 4 (TLR4). Our findings suggest that pyroptosis and the downstream inflammatory response in AMs induced by LPS is a process that is dependent on TLR4-mediated up-regulation of IRF-1. In summary, IRF-1 plays a key role in controlling caspase-1-dependent pyroptosis and inflammation.",2016 Sep 15,"['Wu, Dongdong', 'Pan, Pinhua', 'Su, Xiaoli', 'Zhang, Lemeng', 'Qin, Qingwu', 'Tan, Hongyi', 'Huang, Li', 'Li, Yuanyuan']",Shock,,,True
61d252869a226c4393e4637cb90fa3b4df082ae3,PMC,Evaluation of a programme for ‘Rapid Assessment of Febrile Travelers’ (RAFT): a clinic-based quality improvement initiative,http://dx.doi.org/10.1136/bmjopen-2015-010302,PMC4985841,27473947,CC BY-NC,"BACKGROUND: Fever in the returned traveller is a potential medical emergency warranting prompt attention to exclude life-threatening illnesses. However, prolonged evaluation in the emergency department (ED) may not be required for all patients. As a quality improvement initiative, we implemented an algorithm for rapid assessment of febrile travelers (RAFT) in an ambulatory setting. METHODS: Criteria for RAFT referral include: presentation to the ED, reported fever and travel to the tropics or subtropics within the past year. Exclusion criteria include Plasmodium falciparum malaria, and fulfilment of admission criteria such as unstable vital signs or significant laboratory derangements. We performed a time series analysis preimplementation and postimplementation, with primary outcome of wait time to tropical medicine consultation. Secondary outcomes included number of ED visits averted for repeat malaria testing, and algorithm adherence. RESULTS: From February 2014 to December 2015, 154 patients were seen in the RAFT clinic: 68 men and 86 women. Median age was 36 years (range 16–78 years). Mean time to RAFT clinic assessment was 1.2±0.07 days (range 0–4 days) postimplementation, compared to 5.4±1.8 days (range 0–26 days) prior to implementation (p<0.0001). The RAFT clinic averted 132 repeat malaria screens in the ED over the study period (average 6 per month). Common diagnoses were: traveller's diarrhoea (n=27, 17.5%), dengue (n=12, 8%), viral upper respiratory tract infection (n=11, 7%), chikungunya (n=10, 6.5%), laboratory-confirmed influenza (n=8, 5%) and lobar pneumonia (n=8, 5%). CONCLUSIONS: In addition to provision of more timely care to ambulatory febrile returned travellers, we reduced ED bed-usage by providing an alternate setting for follow-up malaria screening, and treatment of infectious diseases manageable in an outpatient setting, but requiring specific therapy.",2016 Jul 29,"['Jazuli, Farah', 'Lynd, Terence', 'Mah, Jordan', 'Klowak, Michael', 'Jechel, Dale', 'Klowak, Stefanie', 'Ovens, Howard', 'Sabbah, Sam', 'Boggild, Andrea K']",BMJ Open,,,True
965ceefac8caec32604d4e870ae022cd691b7afc,PMC,Evaluation of a programme for ‘Rapid Assessment of Febrile Travelers’ (RAFT): a clinic-based quality improvement initiative,http://dx.doi.org/10.1136/bmjopen-2015-010302,PMC4985841,27473947,CC BY-NC,"BACKGROUND: Fever in the returned traveller is a potential medical emergency warranting prompt attention to exclude life-threatening illnesses. However, prolonged evaluation in the emergency department (ED) may not be required for all patients. As a quality improvement initiative, we implemented an algorithm for rapid assessment of febrile travelers (RAFT) in an ambulatory setting. METHODS: Criteria for RAFT referral include: presentation to the ED, reported fever and travel to the tropics or subtropics within the past year. Exclusion criteria include Plasmodium falciparum malaria, and fulfilment of admission criteria such as unstable vital signs or significant laboratory derangements. We performed a time series analysis preimplementation and postimplementation, with primary outcome of wait time to tropical medicine consultation. Secondary outcomes included number of ED visits averted for repeat malaria testing, and algorithm adherence. RESULTS: From February 2014 to December 2015, 154 patients were seen in the RAFT clinic: 68 men and 86 women. Median age was 36 years (range 16–78 years). Mean time to RAFT clinic assessment was 1.2±0.07 days (range 0–4 days) postimplementation, compared to 5.4±1.8 days (range 0–26 days) prior to implementation (p<0.0001). The RAFT clinic averted 132 repeat malaria screens in the ED over the study period (average 6 per month). Common diagnoses were: traveller's diarrhoea (n=27, 17.5%), dengue (n=12, 8%), viral upper respiratory tract infection (n=11, 7%), chikungunya (n=10, 6.5%), laboratory-confirmed influenza (n=8, 5%) and lobar pneumonia (n=8, 5%). CONCLUSIONS: In addition to provision of more timely care to ambulatory febrile returned travellers, we reduced ED bed-usage by providing an alternate setting for follow-up malaria screening, and treatment of infectious diseases manageable in an outpatient setting, but requiring specific therapy.",2016 Jul 29,"['Jazuli, Farah', 'Lynd, Terence', 'Mah, Jordan', 'Klowak, Michael', 'Jechel, Dale', 'Klowak, Stefanie', 'Ovens, Howard', 'Sabbah, Sam', 'Boggild, Andrea K']",BMJ Open,,,False
8a786d85166401704d2a35fff39726a39909c8f8,PMC,Evaluation of a programme for ‘Rapid Assessment of Febrile Travelers’ (RAFT): a clinic-based quality improvement initiative,http://dx.doi.org/10.1136/bmjopen-2015-010302,PMC4985841,27473947,CC BY-NC,"BACKGROUND: Fever in the returned traveller is a potential medical emergency warranting prompt attention to exclude life-threatening illnesses. However, prolonged evaluation in the emergency department (ED) may not be required for all patients. As a quality improvement initiative, we implemented an algorithm for rapid assessment of febrile travelers (RAFT) in an ambulatory setting. METHODS: Criteria for RAFT referral include: presentation to the ED, reported fever and travel to the tropics or subtropics within the past year. Exclusion criteria include Plasmodium falciparum malaria, and fulfilment of admission criteria such as unstable vital signs or significant laboratory derangements. We performed a time series analysis preimplementation and postimplementation, with primary outcome of wait time to tropical medicine consultation. Secondary outcomes included number of ED visits averted for repeat malaria testing, and algorithm adherence. RESULTS: From February 2014 to December 2015, 154 patients were seen in the RAFT clinic: 68 men and 86 women. Median age was 36 years (range 16–78 years). Mean time to RAFT clinic assessment was 1.2±0.07 days (range 0–4 days) postimplementation, compared to 5.4±1.8 days (range 0–26 days) prior to implementation (p<0.0001). The RAFT clinic averted 132 repeat malaria screens in the ED over the study period (average 6 per month). Common diagnoses were: traveller's diarrhoea (n=27, 17.5%), dengue (n=12, 8%), viral upper respiratory tract infection (n=11, 7%), chikungunya (n=10, 6.5%), laboratory-confirmed influenza (n=8, 5%) and lobar pneumonia (n=8, 5%). CONCLUSIONS: In addition to provision of more timely care to ambulatory febrile returned travellers, we reduced ED bed-usage by providing an alternate setting for follow-up malaria screening, and treatment of infectious diseases manageable in an outpatient setting, but requiring specific therapy.",2016 Jul 29,"['Jazuli, Farah', 'Lynd, Terence', 'Mah, Jordan', 'Klowak, Michael', 'Jechel, Dale', 'Klowak, Stefanie', 'Ovens, Howard', 'Sabbah, Sam', 'Boggild, Andrea K']",BMJ Open,,,False
5d2201d0059d6b9e0702278a74cb46e036434053,PMC,Sendai virus intra-host population dynamics and host immunocompetence influence viral virulence during in vivo passage,http://dx.doi.org/10.1093/ve/vew008,PMC4989884,27774301,CC BY-NC,"In vivo serial passage of non-pathogenic viruses has been shown to lead to increased viral virulence, and although the precise mechanism(s) are not clear, it is known that both host and viral factors are associated with increased pathogenicity. Under- or overnutrition leads to a decreased or dysregulated immune response and can increase viral mutant spectrum diversity and virulence. The objective of this study was to identify the role of viral mutant spectra dynamics and host immunocompetence in the development of pathogenicity during in vivo passage. Because the nutritional status of the host has been shown to affect the development of viral virulence, the diet of animal model reflected two extremes of diets which exist in the global population, malnutrition and obesity. Sendai virus was serially passaged in groups of mice with differing nutritional status followed by transmission of the passaged virus to a second host species, guinea pigs. Viral population dynamics were characterized using deep sequence analysis and computational modeling. Histopathology, viral titer and cytokine assays were used to characterize viral virulence. Viral virulence increased with passage and the virulent phenotype persisted upon passage to a second host species. Additionally, nutritional status of mice during passage influenced the phenotype. Sequencing revealed the presence of several non-synonymous changes in the consensus sequence associated with passage, a majority of which occurred in the hemagglutinin-neuraminidase and polymerase genes, as well as the presence of persistent high frequency variants in the viral population. In particular, an N1124D change in the consensus sequences of the polymerase gene was detected by passage 10 in a majority of the animals. In vivo comparison of an 1124D plaque isolate to a clone with 1124N genotype indicated that 1124D was associated with increased virulence.",2016 Apr 9,"['Peña, José', 'Chen-Harris, Haiyin', 'Allen, Jonathan E.', 'Hwang, Mona', 'Elsheikh, Maher', 'Mabery, Shalini', 'Bielefeldt-Ohmann, Helle', 'Zemla, Adam T.', 'Bowen, Richard A.', 'Borucki, Monica K.']",Virus Evol,,,True
e3529239dbaaf991ccae7b5501f26e531e9be74c,PMC,MERS-CoV recombination: implications about the reservoir and potential for adaptation,http://dx.doi.org/10.1093/ve/vev023,PMC4989901,27774293,CC BY-NC,"Recombination is a process that unlinks neighboring loci allowing for independent evolutionary trajectories within genomes of many organisms. If not properly accounted for, recombination can compromise many evolutionary analyses. In addition, when dealing with organisms that are not obligately sexually reproducing, recombination gives insight into the rate at which distinct genetic lineages come into contact. Since June 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 1,106 laboratory-confirmed infections, with 421 MERS-CoV-associated deaths as of 16 April 2015. Although bats are considered as the likely ultimate source of zoonotic betacoronaviruses, dromedary camels have been consistently implicated as the source of current human infections in the Middle East. In this article, we use phylogenetic methods and simulations to show that MERS-CoV genome has likely undergone numerous recombinations recently. Recombination in MERS-CoV implies frequent co-infection with distinct lineages of MERS-CoV, probably in camels given the current understanding of MERS-CoV epidemiology.",2016 Jan 20,"['Dudas, Gytis', 'Rambaut, Andrew']",Virus Evol,,,True
9f87d0f127411cb1dc51dbd3041aaecc008d7b8d,PMC,MERS-CoV recombination: implications about the reservoir and potential for adaptation,http://dx.doi.org/10.1093/ve/vev023,PMC4989901,27774293,CC BY-NC,"Recombination is a process that unlinks neighboring loci allowing for independent evolutionary trajectories within genomes of many organisms. If not properly accounted for, recombination can compromise many evolutionary analyses. In addition, when dealing with organisms that are not obligately sexually reproducing, recombination gives insight into the rate at which distinct genetic lineages come into contact. Since June 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 1,106 laboratory-confirmed infections, with 421 MERS-CoV-associated deaths as of 16 April 2015. Although bats are considered as the likely ultimate source of zoonotic betacoronaviruses, dromedary camels have been consistently implicated as the source of current human infections in the Middle East. In this article, we use phylogenetic methods and simulations to show that MERS-CoV genome has likely undergone numerous recombinations recently. Recombination in MERS-CoV implies frequent co-infection with distinct lineages of MERS-CoV, probably in camels given the current understanding of MERS-CoV epidemiology.",2016 Jan 20,"['Dudas, Gytis', 'Rambaut, Andrew']",Virus Evol,,,True
723d2ca57cbcc702c68347fb8183376d16d80f1a,PMC,Antioxidant effect of angiotensin (1-7) in the protection of pancreatic β cell function,http://dx.doi.org/10.3892/mmr.2016.5514,PMC4991744,27430410,CC BY-NC-ND,"It is well known that the local renin-angiotensin system (RAS) is activated in the diabetic state, which results in an increase in the level of oxidative stress injury to pancreatic β cells. The angiotensin-converting enzyme 2 (ACE2)/angiotensin (1-7) [Ang (1-7)]/Mas axis is a negative regulator of the classical renin-angiotensin system. In order to investigate the antioxidant effect of Ang (1-7) on pancreatic β cells, INS-1 cells were cultured and oxidative stress was induced by treatment with H(2)O(2). Glucose-stimulated insulin secretion (GSIS), the generation of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and glucose-stimulated calcium (GSCa) responses in β cells were determined following treatment with Ang (1-7). It was observed that H(2)O(2) significantly impaired the insulin secreting function, increased the production of ROS, and also decreased the levels of GSCa and MMP. Pre-treatment with Ang (1-7) alleviated these effects and treatment with A779 [antagonist of Ang (1-7)] prevented the effects of Ang (1-7). Based on these findings, it was concluded that Ang (1-7) can protect pancreatic β cells from oxidative injury and such protection can be blocked by its antagonist A779.",2016 Sep 13,"['Zhang, Fen', 'Liu, Chang', 'Wang, Lei', 'Cao, Xi', 'Wang, Ying Ying', 'Yang, Jin Kui']",Mol Med Rep,,,True
0dc8d11784da63b899dbb2b404be4efd330e4ac3,PMC,Adenoviral vector-based strategies against infectious disease and cancer,http://dx.doi.org/10.1080/21645515.2016.1165908,PMC4994731,27105067,CC BY-NC,"Adenoviral vectors are widely employed against infectious diseases or cancers, as they can elicit specific antibody responses and T cell responses when they are armed with foreign genes as vaccine carriers, and induce apoptosis of the cancer cells when they are genetically modified for cancer therapy. In this review, we summarize the biological characteristics of adenovirus (Ad) and the latest development of Ad vector-based strategies for the prevention and control of emerging infectious diseases or cancers. Strategies to circumvent the pre-existing neutralizing antibodies which dampen the immunogenicity of Ad-based vaccines are also discussed.",2016 Apr 22,"['Zhang, Chao', 'Zhou, Dongming']",Hum Vaccin Immunother,,,True
2891c813ce4dd156d5f56736db5a10a2065c9167,PMC,Active Targeted Drug Delivery for Microbes Using Nano-Carriers,http://dx.doi.org/10.2174/1568026615666150414123157,PMC4997950,25877093,CC BY-NC,"Although vaccines and antibiotics could kill or inhibit microbes, many infectious diseases remain difficult to treat because of acquired resistance and adverse side effects. Nano-carriers-based technology has made significant progress for a long time and is introducing a new paradigm in drug delivery. However, it still has some challenges like lack of specificity toward targeting the infectious site. Nano-carriers utilized targeting ligands on their surface called ‘active target’ provide the promising way to solve the problems like accelerating drug delivery to infectious areas and preventing toxicity or side-effects. In this mini review, we demonstrate the recent studies using the active targeted strategy to kill or inhibit microbes. The four common nano-carriers (e.g. liposomes, nanoparticles, dendrimers and carbon nanotubes) delivering encapsulated drugs are introduced.",2015 Aug,"['Lin, Yung-Sheng', 'Lee, Ming-Yuan', 'Yang, Chih-Hui', 'Huang, Keng-Shiang']",Curr Top Med Chem,,,True
0c3068b22cb2cb50114316f9fed2738a943d2435,PMC,Use of noninvasive ventilation at the pulmonary infection control window for acute respiratory failure in AECOPD patients: A systematic review and meta-analysis based on GRADE approach,http://dx.doi.org/10.1097/MD.0000000000003880,PMC4998464,27310978,CC BY-NC-ND,"The aim of the study was to comprehensively examine the efficacy and safety of noninvasive ventilation used at the pulmonary infection control (PIC) window for acute respiratory failure (ARF) in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Seven electronic databases and relevant resources were searched to identify randomized controlled trials (RCTs) comparing patients using noninvasive ventilation at PIC window with those continuing receiving invasive ventilation. Retrieved citations were screened, risk of bias was assessed, and data were extracted by 2 independent review authors. Overall effect sizes were synthesized by using meta-analyses. Quality of evidence was rated by using Grading of Recommendations, Assessment, Development and Evaluation approach. A total of 17 trials involving 959 participants were included for this review. Compared with continuous invasive ventilation, noninvasive ventilation used at PIC window significantly reduced mortality, ventilator-associated pneumonia, weaning failures, reintubations, duration of invasive ventilation, total duration of mechanical ventilation, length of stay (LOS) in intensive care unit, and LOS in hospital as well as hospital costs. Of these, mortality significantly decreased (risk ratio = 0.27, 95% confidence interval: 0.17–0.42, P < 0.001) without significant heterogeneity (I(2) = 0%, P = 0.99). Quality of evidence regarding the 9 outcomes across the included studies was rated from moderate to low. Use of noninvasive ventilation at PIC window showed beneficial effects across identified trials for ARF in AECOPD patients. Considering the absence of high quality of available evidence and the uncertainty of long-term effect of this intervention, a weak recommendation for clinical practice was generated, and further well-designed and adequately powered RCTs are required to validate this conclusion.",2016 Jun 17,"['Peng, Le', 'Ren, Peng-Wei', 'Liu, Xue-Ting', 'Zhang, Chao', 'Zuo, Hong-Xia', 'Kang, De-Ying', 'Niu, Yu-Ming']",Medicine (Baltimore),,,True
731ee91af20f34fccc9866d85a18b787c16bbe1e,PMC,Detection of Common Respiratory Viruses and Mycoplasma pneumoniae in Patient-Occupied Rooms in Pediatric Wards,http://dx.doi.org/10.1097/MD.0000000000003014,PMC4998743,27057827,CC BY-NC,"Few studies have assessed viral contamination in the rooms of hospital wards. This cross-sectional study evaluated the air and objects in patient-occupied rooms in pediatric wards for the presence of common respiratory viruses and Mycoplasma pneumoniae. Air samplers were placed at a short (60–80 cm) and long (320 cm) distance from the head of the beds of 58 pediatric patients, who were subsequently confirmed to be infected with enterovirus (n = 17), respiratory syncytial virus (RSV) (n = 13), influenza A virus (n = 13), adenovirus (n = 9), or M pneumoniae (n = 6). Swab samples were collected from the surfaces of 5 different types of objects in the patients’ rooms. All air and swab samples were analyzed via real-time quantitative polymerase chain reaction assay for the presence of the above pathogens. All pathogens except enterovirus were detected in the air, on the objects, or in both locations in the patients’ rooms. The detection rates of influenza A virus, adenovirus, and M pneumoniae for the long distance air sampling were 15%, 67%, and 17%, respectively. Both adenovirus and M pneumoniae were detected at very high rates, with high concentrations, on all sampled objects. The respiratory pathogens RSV, influenza A virus, adenovirus, and M pneumoniae were detected in the air and/or on the objects in the pediatric ward rooms. Appropriate infection control measures should be strictly implemented when caring for such patients.",2016 Apr 8,"['Wan, Gwo-Hwa', 'Huang, Chung-Guei', 'Chung, Fen-Fang', 'Lin, Tzou-Yien', 'Tsao, Kuo-Chien', 'Huang, Yhu-Chering']",Medicine (Baltimore),,,True
ecf580f9baf30b1e7c860068c834f34d175dbda0,PMC,An siRNA screen for ATG protein depletion reveals the extent of the unconventional functions of the autophagy proteome in virus replication,http://dx.doi.org/10.1083/jcb.201602046,PMC5004442,27573464,CC BY-NC-SA,"Autophagy is a catabolic process regulated by the orchestrated action of the autophagy-related (ATG) proteins. Recent work indicates that some of the ATG proteins also have autophagy-independent roles. Using an unbiased siRNA screen approach, we explored the extent of these unconventional functions of ATG proteins. We determined the effects of the depletion of each ATG proteome component on the replication of six different viruses. Our screen reveals that up to 36% of the ATG proteins significantly alter the replication of at least one virus in an unconventional fashion. Detailed analysis of two candidates revealed an undocumented role for ATG13 and FIP200 in picornavirus replication that is independent of their function in autophagy as part of the ULK complex. The high numbers of unveiled ATG gene-specific and pathogen-specific functions of the ATG proteins calls for caution in the interpretation of data, which rely solely on the depletion of a single ATG protein to specifically ablate autophagy.",2016 Aug 29,"['Mauthe, Mario', 'Langereis, Martijn', 'Jung, Jennifer', 'Zhou, Xingdong', 'Jones, Alex', 'Omta, Wienand', 'Tooze, Sharon A.', 'Stork, Björn', 'Paludan, Søren Riis', 'Ahola, Tero', 'Egan, Dave', 'Behrends, Christian', 'Mokry, Michal', 'de Haan, Cornelis', 'van Kuppeveld, Frank', 'Reggiori, Fulvio']",J Cell Biol,,,True
c3c4e7af686b1e9a1aa37785458382ec75849265,PMC,An siRNA screen for ATG protein depletion reveals the extent of the unconventional functions of the autophagy proteome in virus replication,http://dx.doi.org/10.1083/jcb.201602046,PMC5004442,27573464,CC BY-NC-SA,"Autophagy is a catabolic process regulated by the orchestrated action of the autophagy-related (ATG) proteins. Recent work indicates that some of the ATG proteins also have autophagy-independent roles. Using an unbiased siRNA screen approach, we explored the extent of these unconventional functions of ATG proteins. We determined the effects of the depletion of each ATG proteome component on the replication of six different viruses. Our screen reveals that up to 36% of the ATG proteins significantly alter the replication of at least one virus in an unconventional fashion. Detailed analysis of two candidates revealed an undocumented role for ATG13 and FIP200 in picornavirus replication that is independent of their function in autophagy as part of the ULK complex. The high numbers of unveiled ATG gene-specific and pathogen-specific functions of the ATG proteins calls for caution in the interpretation of data, which rely solely on the depletion of a single ATG protein to specifically ablate autophagy.",2016 Aug 29,"['Mauthe, Mario', 'Langereis, Martijn', 'Jung, Jennifer', 'Zhou, Xingdong', 'Jones, Alex', 'Omta, Wienand', 'Tooze, Sharon A.', 'Stork, Björn', 'Paludan, Søren Riis', 'Ahola, Tero', 'Egan, Dave', 'Behrends, Christian', 'Mokry, Michal', 'de Haan, Cornelis', 'van Kuppeveld, Frank', 'Reggiori, Fulvio']",J Cell Biol,,,False
4b3d6bca8bfe315d03331cba07299570e2ce7fad,PMC,At the crossroads of autophagy and infection: Noncanonical roles for ATG proteins in viral replication,http://dx.doi.org/10.1083/jcb.201608032,PMC5004452,27573461,CC BY-NC-SA,"Autophagy-related (ATG) proteins have increasingly demonstrated functions other than cellular self-eating. In this issue, Mauthe et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201602046) conduct an unbiased RNA interference screen of the ATG proteome to reveal numerous noncanonical roles for ATG proteins during viral infection.",2016 Aug 29,"['Solvik, Tina', 'Debnath, Jayanta']",J Cell Biol,,,True
b891efc6e1419713b05ff7d89b26d260478c28df,PMC,Tuberculosis prevention in healthcare workers in China 10 years after the severe acute respiratory syndrome pandemic,http://dx.doi.org/10.1183/23120541.00015-2015,PMC5005135,27730135,CC BY-NC,BSL3 and respiratory isolation wards protect healthcare workers from nosocomial TB infection in China http://ow.ly/PGvSl,2015 Aug 21,"['Deng, Yunfeng', 'Li, Yan', 'Wang, Fengtian', 'Gao, Dachuan', 'Li, Liang', 'Teeter, Larry D.', 'Graviss, Edward A.', 'Ma, Xin']",ERJ Open Res,,,True
8cb96ebaf1320867609839df21072f96631e9015,PMC,Distinctive clinical features of HPeV-3 infection in 2 neonates with a sepsis-like illness,http://dx.doi.org/10.3345/kjp.2016.59.7.308,PMC5007427,27588032,CC BY-NC,"We report a human parechovirus-3 (HPeV-3) infection in 2 neonates who had prolonged fever (>5 days) with palmar-plantar erythema. This distinctive rash was observed 4–5 days after fever onset, just before defervescence. Elevated aspartate aminotransferase, lactate dehydrogenase, and ferritin levels were characteristic laboratory findings in the 2 cases, suggesting tissue damage caused by hypercytokinemia. Case 1 was treated with intravenous immunoglobulin, considering the possibility of severe systemic inflammatory responses. The initial ferritin level was 385 ng/mL (range, 0–400 ng/mL); however, the level increased to 2,581 ng/dL on day 5 after fever onset. Case 2 presented with milder clinical symptoms, and the patient recovered spontaneously. HPeV-3 was detected in cerebrospinal fluid and/or blood samples, but no other causative agents were detected. The findings from our cases, in accordance with recent studies, suggest that clinical features such as palmar-plantar erythema and/or hyperferritinemia might be indicators of HPeV-3 infection in neonates with sepsis-like illness. In clinical practice, where virology testing is not easily accessible, clinical features such as palmar-plantar erythema and/or hyperferritinemia might be helpful to diagnose HPeV-3 infection.",2016 Jul 31,"['Yeom, Jung Sook', 'Park, Ji Sook', 'Seo, Ji-Hyun', 'Park, Eun Sil', 'Lim, Jae-Young', 'Park, Chan-Hoo', 'Woo, Hyang-Ok', 'Youn, Hee-Shang', 'Lee, Ok Jeong', 'Han, Tae-Hee', 'Chung, Ju-Young']",Korean J Pediatr,,,True
e53183332e36bd1da462d867651d2e259d341567,PMC,The Independence of Ontario's Public Health Units: Does Governing Structure Matter?,,PMC5008133,27585028,CC BY-NC,"Do autonomous health units fulfil their mandate better than ones that are integrated into municipal structures? Many observers of Ontario's public health system seem to think so, but this assumption is based on very little evidence. This paper seeks to help fill this gap by grounding a comparison of the spending growth of two health units with different governing structures in the multilevel governance literature. The study finds that, after an increase in provincial funding, an autonomous health unit, the Middlesex-London Health Unit, behaved more in accordance with provincial expectations than Hamilton Public Health Services, which is integrated into the City of Hamilton. The paper contributes by providing theoretical and empirical explanations for variation among local health units.",2016 Aug,"Lyons, Joseph",Healthc Policy,,,True
ac209c3960cd2a4996e560dfefb2bfdc924b6cdb,PMC,N-Myc expression enhances the oncolytic effects of vesicular stomatitis virus in human neuroblastoma cells,http://dx.doi.org/10.1038/mto.2016.5,PMC5008254,27626059,CC BY-NC-ND,"N-myc oncogene amplification is associated but not present in all cases of high-risk neuroblastoma (NB). Since oncogene expression could often modulate sensitivity to oncolytic viruses, we wanted to examine if N-myc expression status would determine virotherapy efficacy to high-risk NB. We showed that induction of exogenous N-myc in a non-N-myc-amplified cell line background (TET-21N) increased susceptibility to oncolytic vesicular stomatitis virus (mutant VSVΔM51) and alleviated the type I IFN-induced antiviral state. Cells with basal N-myc, on the other hand, were less susceptible to virus-induced oncolysis and established a robust IFN-mediated antiviral state. The same effects were also observed in NB cell lines with and without N-myc amplification. Microarray analysis showed that N-myc overexpression in TET-21N cells downregulated IFN-stimulated genes (ISGs) with known antiviral functions. Furthermore, virus infection caused significant changes in global gene expression in TET-21N cells overexpressing N-myc. Such changes involved ISGs with various functions. Therefore, the present study showed that augmented susceptibility to VSVΔM51 by N-myc at least involves downregulation of ISGs with antiviral functions and alleviation of the IFN-stimulated antiviral state. Our studies suggest the potential utility of N-myc amplification/overexpression as a predictive biomarker of virotherapy response for high-risk NB using IFN-sensitive oncolytic viruses.",2016 Mar 16,"['Corredor, Juan C', 'Redding, Nicole', 'Bloté, Karen', 'Robbins, Stephen M', 'Senger, Donna L', 'Bell, John C', 'Beaudry, Paul']",Mol Ther Oncolytics,,,True
99fded56685ed6b4746525a997568696de2befd4,PMC,Network analysis of host–virus communities in bats and rodents reveals determinants of cross‐species transmission,http://dx.doi.org/10.1111/ele.12491,PMC5014217,26299267,CC BY-NC,"Bats are natural reservoirs of several important emerging viruses. Cross‐species transmission appears to be quite common among bats, which may contribute to their unique reservoir potential. Therefore, understanding the importance of bats as reservoirs requires examining them in a community context rather than concentrating on individual species. Here, we use a network approach to identify ecological and biological correlates of cross‐species virus transmission in bats and rodents, another important host group. We show that given our current knowledge the bat viral sharing network is more connected than the rodent network, suggesting viruses may pass more easily between bat species. We identify host traits associated with important reservoir species: gregarious bats are more likely to share more viruses and bats which migrate regionally are important for spreading viruses through the network. We identify multiple communities of viral sharing within bats and rodents and highlight potential species traits that can help guide studies of novel pathogen emergence.",2015 Nov 24,"['Luis, Angela D.', ""O'Shea, Thomas J."", 'Hayman, David T. S.', 'Wood, James L. N.', 'Cunningham, Andrew A.', 'Gilbert, Amy T.', 'Mills, James N.', 'Webb, Colleen T.']",Ecol Lett,,,True
51a24b884e01df122d889f1133e7727e2478be24,PMC,Co-infection with two strains of Brome mosaic bromovirus reveals common RNA recombination sites in different hosts,http://dx.doi.org/10.1093/ve/vev021,PMC5014487,27774290,CC BY-NC,"We have previously reported intra-segmental crossovers in Brome mosaic virus (BMV) RNAs. In this work, we studied the homologous recombination of BMV RNA in three different hosts: barley (Hordeum vulgare), Chenopodium quinoa, and Nicotiana benthamiana that were co-infected with two strains of BMV: Russian (R) and Fescue (F). Our work aimed at (1) establishing the frequency of recombination, (2) mapping the recombination hot spots, and (3) addressing host effects. The F and R nucleotide sequences differ from each other at many translationally silent nucleotide substitutions. We exploited this natural variability to track the crossover sites. Sequencing of a large number of cDNA clones revealed multiple homologous crossovers in each BMV RNA segment, in both the whole plants and protoplasts. Some recombination hot spots mapped at similar locations in different hosts, suggesting a role for viral factors, but other sites depended on the host. Our results demonstrate the chimeric (‘mosaic’) nature of the BMV RNA genome.",2015 Dec 23,"['Kolondam, Beivy', 'Rao, Parth', 'Sztuba-Solinska, Joanna', 'Weber, Philipp H.', 'Dzianott, Aleksandra', 'Johns, Mitrick A.', 'Bujarski, Jozef J.']",Virus Evol,,,True
bbf70aeba7b4a4b8d96db253e673881ac220e36c,PMC,Hemagglutinin-targeting Artificial MicroRNAs Expressed by Adenovirus Protect Mice From Different Clades of H5N1 Infection,http://dx.doi.org/10.1038/mtna.2016.25,PMC5014526,27093169,CC BY-NC-ND,"Influenza virus (IV) is a continuously evolving virus that widely spreads in humans and contributes to substantial morbidity and mortality. Re-emergence of human infection with avian influenza virus H5N1 poses extra challenge to IV control. Artificial microRNA (amiRNA)-mediated RNA interference has become a powerful antiviral approach due to its high specificity and rapid effect. Here, we designed several amiRNAs targeting the hemagglutinin gene of H5N1, a major determinant of pathogenicity. Expression and delivery efficiency were enhanced by presenting functional amiRNA with chimpanzee adenovirus serotype 68 (AdC68). One amiRNA, HA-1405, significantly limited H5N1 replication in vitro and inhibited 96.7% of clade 2.3.2 replication. AdC68-conjugated HA-1405 treatment remarkably decreased different clades of H5N1 plaque formation in Madin–Darby canine kidney cells. Moreover, prophylactic administration with rAd(HA-1405) markedly alleviated clinical symptoms and reduced ~3- to 40-folds of lung viral RNA copies against four clades of H5N1 in Institute of Cancer Research (ICR) mice. Our results further showed that rAd(HA-1405) conferred 70 and 40% immediate protection against lethal clade 2.3.2 and clade 2.3.4 H5N1 challenge, respectively. In conclusion, these data provided information that HA-targeting amiRNA delivered by AdC68 could be pursued as a potential agent for highly pathogenic avian influenza viruses prevention.",2016 Apr 19,"['Tang, Xinying', 'Zhang, Hongbo', 'Song, Yufeng', 'Zhou, Dongming', 'Wang, Jieru']",Mol Ther Nucleic Acids,,,True
2ea1b31d8e9b2d8e4f980c0fd269f75dad4d1d75,PMC,"In the era of corona virus: health care professionals’ knowledge, attitudes, and practice of hand hygiene in Saudi primary care centers: a cross-sectional study",http://dx.doi.org/10.3402/jchimp.v6.32151,PMC5016750,27609728,CC BY-NC,"BACKGROUND: Hand hygiene is one of the essential means to prevent the spread of infections. The aim of this study was to assess the knowledge, attitudes, and practice (KAP) of hand hygiene in primary care settings. METHODS: A cross-sectional study using a self-reported questionnaire was conducted in primary care settings located in Riyadh, Kingdom of Saudi Arabia, under the service of King Abdulaziz Medical City (KAMC). The Institutional Review Board of KAMC Research Centre approved the study. Data were analyzed using IBM SPSS software. RESULTS: A total of 237 participants were included in the analysis. Participants who received hand hygiene training within the last 3 years (2012–2014) scored higher on a knowledge scale. Generally, there was an overall positive attitude from participants toward hand hygiene practice. In total, 87.54% acknowledged that they routinely used alcohol-based hand rub, 87.4% had sufficiently decontaminated hands even under high work pressure, and 78.6% addressed that this practice was not affected by less compliant colleagues. CONCLUSION: Practicing hand hygiene was suggested to be influenced by variables related to the environmental context, social pressure, and individual attitudes toward hand hygiene. We believe that addressing beliefs, attitudes, capacity, and supportive infrastructures to sustain hand-hygiene routine behaviors are important components of an implementation strategy in enhancing health care workers’ KAP of hand hygiene.",2016 Sep 7,"['Alfahan, Ali', 'Alhabib, Samia', 'Abdulmajeed, Imad', 'Rahman, Saeed', 'Bamuhair, Samira']",J Community Hosp Intern Med Perspect,,,True
9c159594c91b5f2608137dd010930f11a9baf209,PMC,Bulk production of the antiviral lectin griffithsin,http://dx.doi.org/10.1111/pbi.12433,PMC5016770,26176205,CC BY-NC-ND,"Application of plant‐based protein expression systems for bulk production of recombinant protein pharmaceuticals is building momentum. There are considerable regulatory challenges to consider in commercialization of plant‐made pharmaceuticals (PMPs), some of which are inherent to plant‐production systems and others that are common with other production systems, but are new to PMPs because of the youth of the industry. In this review, we discuss our recent and ongoing experience with bulk production of the HIV microbicide candidate, griffithsin (GRFT), utilizing plant‐based transient protein expression, with specific focus on areas relevant to commercial manufacturing of bulk GRFT active pharmaceutical ingredient (API). Analytical programs have been developed for the qualification and monitoring of both the expression vector system and the API detailing our experience and plans for each. Monitoring postpurification protein modifications are discussed in relation to stability and safety programs. Expression, processing and analytics programs are associated with increased manufacturing costs in current good manufacturing practice (cGMP) production because of the required qualification testing. The impact of these costs on the overall cost of goods is particularly relevant to GRFT manufacturing because GRFT, as an HIV microbicide, is most needed in populations at high risk for HIV exposure in resource‐poor countries. Consequently, GRFT for microbicide applications is a very cost‐sensitive recombinant PMP. We have therefore emphasized maintaining a low cost of goods. We provide a review of the literature on the economics of PMPs with various expression systems and how they may impact production costs and complexity.",2015 Oct 14,"['Fuqua, Joshua L.', 'Hamorsky, Krystal', 'Khalsa, Guruatma', 'Matoba, Nobuyuki', 'Palmer, Kenneth E.']",Plant Biotechnol J,,,True
91482c04f233e544d1d46410760fa946c48d16dc,PMC,Identification of Interferon-Stimulated Genes with Antiretroviral Activity,http://dx.doi.org/10.1016/j.chom.2016.08.005,PMC5026698,27631702,CC BY-NC-ND,"Interferons (IFNs) exert their anti-viral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). The activity of known ISGs is insufficient to account for the antiretroviral effects of IFN, suggesting that ISGs with antiretroviral activity are yet to be described. We constructed an arrayed library of ISGs from rhesus macaques and tested the ability of hundreds of individual macaque and human ISGs to inhibit early and late replication steps for 11 members of the retroviridae from various host species. These screens uncovered numerous ISGs with antiretroviral activity at both the early and late stages of virus replication. Detailed analyses of two antiretroviral ISGs indicate that indoleamine 2,3-dioxygenase 1 (IDO1) can inhibit retroviral replication by metabolite depletion while tripartite motif-56 (TRIM56) accentuates ISG induction by IFNα and inhibits the expression of late HIV-1 genes. Overall, these studies reveal numerous host proteins that mediate the antiretroviral activity of IFNs.",2016 Sep 14,"['Kane, Melissa', 'Zang, Trinity\xa0M.', 'Rihn, Suzannah\xa0J.', 'Zhang, Fengwen', 'Kueck, Tonya', 'Alim, Mudathir', 'Schoggins, John', 'Rice, Charles\xa0M.', 'Wilson, Sam\xa0J.', 'Bieniasz, Paul\xa0D.']",Cell Host Microbe,,,False
5b252be4b0ef235379d048786133fbe4a2af3976,PMC,Identification of Interferon-Stimulated Genes with Antiretroviral Activity,http://dx.doi.org/10.1016/j.chom.2016.08.005,PMC5026698,27631702,CC BY-NC-ND,"Interferons (IFNs) exert their anti-viral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). The activity of known ISGs is insufficient to account for the antiretroviral effects of IFN, suggesting that ISGs with antiretroviral activity are yet to be described. We constructed an arrayed library of ISGs from rhesus macaques and tested the ability of hundreds of individual macaque and human ISGs to inhibit early and late replication steps for 11 members of the retroviridae from various host species. These screens uncovered numerous ISGs with antiretroviral activity at both the early and late stages of virus replication. Detailed analyses of two antiretroviral ISGs indicate that indoleamine 2,3-dioxygenase 1 (IDO1) can inhibit retroviral replication by metabolite depletion while tripartite motif-56 (TRIM56) accentuates ISG induction by IFNα and inhibits the expression of late HIV-1 genes. Overall, these studies reveal numerous host proteins that mediate the antiretroviral activity of IFNs.",2016 Sep 14,"['Kane, Melissa', 'Zang, Trinity\xa0M.', 'Rihn, Suzannah\xa0J.', 'Zhang, Fengwen', 'Kueck, Tonya', 'Alim, Mudathir', 'Schoggins, John', 'Rice, Charles\xa0M.', 'Wilson, Sam\xa0J.', 'Bieniasz, Paul\xa0D.']",Cell Host Microbe,,,False
ef941da966e9e5a3f54360843a1d3aeefd37e598,PMC,Diversity in a honey bee pathogen: first report of a third master variant of the Deformed Wing Virus quasispecies,http://dx.doi.org/10.1038/ismej.2015.178,PMC5029213,26574686,CC BY-NC-SA,"Treatment of emerging RNA viruses is hampered by the high mutation and replication rates that enable these viruses to operate as a quasispecies. Declining honey bee populations have been attributed to the ectoparasitic mite Varroa destructor and its affiliation with Deformed Wing Virus (DWV). In the current study we use next-generation sequencing to investigate the DWV quasispecies in an apiary known to suffer from overwintering colony losses. We show that the DWV species complex is made up of three master variants. Our results indicate that a new DWV Type C variant is distinct from the previously described types A and B, but together they form a distinct clade compared with other members of the Iflaviridae. The molecular clock estimation predicts that Type C diverged from the other variants ∼319 years ago. The discovery of a new master variant of DWV has important implications for the positive identification of the true pathogen within global honey bee populations.",2016 May 17,"['Mordecai, Gideon J', 'Wilfert, Lena', 'Martin, Stephen J', 'Jones, Ian M', 'Schroeder, Declan C']",ISME J,,,True
0a003aa69f43cee4357f1e943df79a8b87c0a88e,PMC,Identification of Leukotoxin and other vaccine candidate proteins in a Mannheimia haemolytica commercial antigen,http://dx.doi.org/10.1016/j.heliyon.2016.e00158,PMC5035357,27699279,CC BY-NC-ND,"Bovine Respiratory Disease is the most costly disease that affects beef and dairy cattle industry. Its etiology is multifactorial, arising from predisposing environmental stress conditions as well as the action of several different respiratory pathogens. This situation has hindered the development of effective control strategies. Although different type of vaccines are available, many currently marketed vaccines are based on inactivated cultures of the main viral and bacterial agents involved in this pathology. The molecular composition of commercial veterinary vaccines is a critical issue. The present work aims to define at the proteomic level the most relevant valence of a line of commercial respiratory vaccines widely used in Central and South America. Since Mannheimia haemolytica is responsible for most of the disease associated morbid-mortality, we focused on the main proteins secreted by this pathogen, in particular Leukotoxin A, its main virulence factor. By Western blot analysis and mass spectrometry, Leukotoxin A was identified as a major component of M. haemolytica culture supernatants. We also identified other ten M. haemolytica proteins, including outer membrane proteins, periplasmic transmembrane solute transporters and iron binding proteins, which are relevant to achieve protective immunity against the pathogen. This work allowed a detailed molecular characterization of this vaccine component, providing evidence of its quality and efficacy. Furthermore, our results contributed to the identification of several proteins of interest as subunit vaccine candidates.",2016 Sep 19,"['Tucci, Paula', 'Estevez, Verónica', 'Becco, Lorena', 'Cabrera-Cabrera, Florencia', 'Grotiuz, Germán', 'Reolon, Eduardo', 'Marín, Mónica']",Heliyon,,,False
80f0bc76680d66fa78c6665807bedcf74b190751,PMC,Development and evaluation of a competitive enzyme-linked immunosorbent assay using a monoclonal antibody for diagnosis of severe fever with thrombocytopenia syndrome virus in bovine sera,http://dx.doi.org/10.4142/jvs.2016.17.3.307,PMC5037297,26435543,CC BY-NC,"Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV), a phlebovirus in the family Bunyaviridae, is an emerging tick-borne infectious disease that impacts humans. This disease manifests as a decreased blood cell count and multi-organ failure, with a case-fatality rate of more than 12% in China. Because vaccines or antiviral drugs for the treatment of this disease are not available, monitoring the SFTS circulation in animals and controlling the tick-mammal cycle are important for preventing SFTS. Monoclonal antibodies against the recombinant nucleoprotein of SFTSV were generated to develop a competitive enzyme-linked immunosorbent assay (cELISA) for the detection of antibodies against SFTSV infection in cattle. The specificity and sensitivity of cELISA was assessed by comparing the results of this assay to those of an immunofluorescence assay (IFA). The results of the cELISA using 416 field bovine serum samples and laboratory-immunized positive sera showed 98.1% consistency with those of the IFA. The cELISA used in this study did not show cross-reactivity with antisera against other viral cattle diseases. The cELISA presented in this study can be applied to detect antibodies against SFTSV in cattle.",2016 Sep 20,"['Lee, Hyojin', 'Kim, Eun-Ju', 'Song, Jae-Young', 'Choi, Jeong Soo', 'Lee, Ji Youn', 'Cho, In-Soo', 'Shin, Yeun-Kyung']",J Vet Sci,,,True
fbef90f2882028bd73ad59567fe2e33ebb128c08,PMC,Development and evaluation of a competitive enzyme-linked immunosorbent assay using a monoclonal antibody for diagnosis of severe fever with thrombocytopenia syndrome virus in bovine sera,http://dx.doi.org/10.4142/jvs.2016.17.3.307,PMC5037297,26435543,CC BY-NC,"Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV), a phlebovirus in the family Bunyaviridae, is an emerging tick-borne infectious disease that impacts humans. This disease manifests as a decreased blood cell count and multi-organ failure, with a case-fatality rate of more than 12% in China. Because vaccines or antiviral drugs for the treatment of this disease are not available, monitoring the SFTS circulation in animals and controlling the tick-mammal cycle are important for preventing SFTS. Monoclonal antibodies against the recombinant nucleoprotein of SFTSV were generated to develop a competitive enzyme-linked immunosorbent assay (cELISA) for the detection of antibodies against SFTSV infection in cattle. The specificity and sensitivity of cELISA was assessed by comparing the results of this assay to those of an immunofluorescence assay (IFA). The results of the cELISA using 416 field bovine serum samples and laboratory-immunized positive sera showed 98.1% consistency with those of the IFA. The cELISA used in this study did not show cross-reactivity with antisera against other viral cattle diseases. The cELISA presented in this study can be applied to detect antibodies against SFTSV in cattle.",2016 Sep 20,"['Lee, Hyojin', 'Kim, Eun-Ju', 'Song, Jae-Young', 'Choi, Jeong Soo', 'Lee, Ji Youn', 'Cho, In-Soo', 'Shin, Yeun-Kyung']",J Vet Sci,,,False
19e06aea8fb63db41815a99ec32f8915b80609cd,PMC,Development and evaluation of a competitive enzyme-linked immunosorbent assay using a monoclonal antibody for diagnosis of severe fever with thrombocytopenia syndrome virus in bovine sera,http://dx.doi.org/10.4142/jvs.2016.17.3.307,PMC5037297,26435543,CC BY-NC,"Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV), a phlebovirus in the family Bunyaviridae, is an emerging tick-borne infectious disease that impacts humans. This disease manifests as a decreased blood cell count and multi-organ failure, with a case-fatality rate of more than 12% in China. Because vaccines or antiviral drugs for the treatment of this disease are not available, monitoring the SFTS circulation in animals and controlling the tick-mammal cycle are important for preventing SFTS. Monoclonal antibodies against the recombinant nucleoprotein of SFTSV were generated to develop a competitive enzyme-linked immunosorbent assay (cELISA) for the detection of antibodies against SFTSV infection in cattle. The specificity and sensitivity of cELISA was assessed by comparing the results of this assay to those of an immunofluorescence assay (IFA). The results of the cELISA using 416 field bovine serum samples and laboratory-immunized positive sera showed 98.1% consistency with those of the IFA. The cELISA used in this study did not show cross-reactivity with antisera against other viral cattle diseases. The cELISA presented in this study can be applied to detect antibodies against SFTSV in cattle.",2016 Sep 20,"['Lee, Hyojin', 'Kim, Eun-Ju', 'Song, Jae-Young', 'Choi, Jeong Soo', 'Lee, Ji Youn', 'Cho, In-Soo', 'Shin, Yeun-Kyung']",J Vet Sci,,,False
df62b9ff3b2b95896d4b90ccefc9f3d756be1abf,PMC,Emergency treatment and nursing of children with severe pneumonia complicated by heart failure and respiratory failure: 10 case reports,http://dx.doi.org/10.3892/etm.2016.3558,PMC5038202,27698703,CC BY-NC-ND,"Pneumonia refers to lung inflammation caused by different pathogens or other factors, and is a common pediatric disease occurring in infants and young children. It is closely related to the anatomical and physiological characteristics of infants and young children and is more frequent during winter and spring, or sudden changes in temperature. Pneumonia is a serious disease that poses a threat to children's health and its morbidity and mortality rank first, accounting for 24.5–65.2% of pediatric inpatients. Due to juvenile age, severe illness and rapid changes, children often suffer acute heart failure, respiratory failure and even toxic encephalopathy at the same time. The concurrence in different stages of the process of emergency treatment tends to relapse, which directly places the lives of these children at risk. Severe pneumonia constitutes one of the main causes of infant mortality. In the process of nursing children with severe pneumonia, intensive care was provided, including condition assessment and diagnosis, close observation of disease, keeping the airway unblocked, rational oxygen therapy, prevention and treatment of respiratory and circulatory failure, support of vital organs, complications, and health education. The inflammatory response was proactively controlled, to prevent suffocation and reduce mortality. In summary, positive and effective nursing can promote the rehabilitation of children patients, which can be reinforced with adequate communication with the parents and/or caretakers.",2016 Oct 29,"['Li, Wanli', 'An, Xinjiang', 'Fu, Mingyu', 'Li, Chunli']",Exp Ther Med,,,True
ee4e69f64556d94a481199be5f3b517f1de5d947,PMC,Effective factors in expansion of medical tourism in Iran,,PMC5038994,27683650,CC BY-NC,"Background: Medical tourism (MT) refers to circumstances in which people travel for medical treatments. The present study focuses on determining factors affecting MT in Iran. Methods: The study uses a mixed method approach. Initially, through a qualitative study, 12 experts were interviewed deeply; then, 22 participants in three equal focus groups expressed their ideas about growth and development of MT in Iran. Based on the expressed ideas, 120 factors were identified and accordingly a structured questionnaire was developed. Some members from the focus groups confirmed the questionnaire’s face and content validity. The reliability of pertinent items was confirmed using Cronbach’s alpha=0.8. Afterwards, 61 eligible subjects filled out this questionnaire. Results: The findings showed that ""healthcare quality"" and ""high level of expertise"" are two most attractive factors in MT. However, other factors such as ""healthcare costs"", and ""visa facilities"" are among key factors as well. Also, the role of ""the healthcare providers"" was found to be more prominent than the roles of ""the government"" and ""the general tourist services"". Conclusion: Although some attractive MT factors are present currently, MT expansion to a desirable level in Iran requires a comprehensive plan of which its factors were discussed in this paper.",2016 Sep 5,"['Rezaee, Reza', 'Mohammadzadeh, Mehdi']",Med J Islam Repub Iran,,,True
b89434ac6bfe4104f4c207a770a6858413e383cd,PMC,Available Evidence of Association between Zika Virus and Microcephaly,http://dx.doi.org/10.4103/0366-6999.190672,PMC5040022,27647195,CC BY-NC-SA,"OBJECTIVE: To clarify the possible association between the Zika virus (ZIKV) and microcephaly and understand where we are in terms of research and the debate on the causation between mild maternal clinical features and severe fetal microcephaly. DATA SOURCES: We did a comprehensive literature review with the keywords “zika” and/or “microcephaly” from inception to May 27, 2016, with PubMed. STUDY SELECTION: Studies were included and analyzed if they met all of the following criteria: “probable or confirmed infant microcephaly” and “probable or confirmed ZIKV infection among mothers or infants”. RESULTS: We emphasize the diagnosis of ZIKV infection, including maternal clinical manifestations, maternal and fetal laboratory confirmation, and possible autopsy if need. Other confounders that may lead to microcephaly should be excluded from the study. We presented the results from clinical manifestations of ZIKV infection, testing methods evolving but the mechanism of microcephaly uncertain, flexible definition challenging the diagnosis of microcephaly, and limited causal reference on pregnant women. We made analog comparison of severe acute respiratory syndrome and chikungunya virus in terms of DNA mutation and global movement to provide further research recommendation. The chance of catch-up growth may decrease the number of pervious “diagnosed” microcephaly. CONCLUSIONS: There are some evidence available through mice models and direct isolation of ZIKV in affected pregnancies on kindly causal relationship but not convincible enough. We analyzed and presented the weakness or limitation of published reports with the desire to shed light to further study directions.",2016 Oct 5,"['Wu, Jing', 'Huang, Da-Yong', 'Ma, Jun-Tao', 'Ma, Ying-Hua', 'Hu, Yi-Fei']",Chin Med J (Engl),,,True
3fad6dea4f2f9afda7699aa3b79d11b4ddfb57fd,PMC,Phenol-Rich Compounds Sweet Gel: A Statistically More Effective Antibiotic than Cloxacillin Against Pseudomonas Aeruginosa,http://dx.doi.org/10.3831/KPI.2016.19.026,PMC5043089,27695634,CC BY-NC,"OBJECTIVES: The purpose of this study was to obtain a natural antibiotic from Phenol-rich compounds; for the dressing and the treatment of chronic wounds. METHODS: The Phenol-rich compound sweet gel was prepared by blending four natural herbal extracts, Acacia catechu (L.F.), Momia (Shilajit), Castanea sativa, and Ephedra sinica stapf, with combination of a sweet gel medium, including honey, maple saps, Phoenix dactylifera L. (date), pomegranate extract and Azadirachta indica gum as a stabilizer. The combinations were screened by using a well-diffusion assay with cloxacillin as a control. Pseudomonas spp. was tested with our novel antimicrobial compound. The zones of inhibition in agar culture were measured for each individual component and for the compound, and the results were compared with those of the control group which had been treated with cloxacillin. Data were expressed as means ± standard deviations. Quantitative analyses were performed using the paired t-test. RESULTS: The antibiotic effect of the Phenol-rich compound sweet gel was statistically shown to be more significant than that of cloxacillin against Pseudomonas aeruginosa (P < 0.05). CONCLUSION: Our novel approach to fighting the antibiotic resistance of Pseudomonas proved to be successful. The Phenol-rich compound sweet gel was found to be suitable for use as an alternative medicine and bioactive dressing material, for the treatment of patients with various types of wounds, including burns, venous leg ulcers, ulcers of various etiologies, leg ulcers on the feet of diabetic, unhealed graft sampling sites, abscesses, boils, surgical wounds, necrotic process, post-operative and neonatal wound infection, and should be considered as an alternative to the usual methods of cure.",2016 Sep,"['Dashtdar, Mehrab', 'Dashtdar, Mohammad Reza', 'Dashtdar, Babak', 'Khan, Gazala Afreen', 'Kardi, Karima']",J Pharmacopuncture,,,True
40470023462dcfcc8ed653d73a5dd255699abcad,PMC,An Ecological Framework of the Human Virome Provides Classification of Current Knowledge and Identifies Areas of Forthcoming Discovery,,PMC5045143,27698618,CC BY-NC,"Recent advances in sequencing technologies have opened the door for the classification of the human virome. While taxonomic classification can be applied to the viruses identified in such studies, this gives no information as to the type of interaction the virus has with the host. As follow-up studies are performed to address these questions, the description of these virus-host interactions would be greatly enriched by applying a standard set of definitions that typify them. This paper describes a framework with which all members of the human virome can be classified based on principles of ecology. The scaffold not only enables categorization of the human virome, but can also inform research aimed at identifying novel virus-host interactions.",2016 Sep 30,"Parker, Michael T.",Yale J Biol Med,,,True
46768e7c839a7f4de0d5a73d25897f948b4eac30,PMC,"Increase in Middle East Respiratory Syndrome-Coronavirus Cases in Saudi Arabia Linked to Hospital Outbreak With Continued Circulation of Recombinant Virus, July 1–August 31, 2015",http://dx.doi.org/10.1093/ofid/ofw165,PMC5047409,27704019,CC BY-NC-ND,"During July–August 2015, the number of cases of Middle East respiratory syndrome (MERS) reported from Saudi Arabia increased dramatically. We reviewed the 143 confirmed cases from this period and classified each based upon likely transmission source. We found that the surge in cases resulted predominantly (90%) from secondary transmission largely attributable to an outbreak at a single healthcare facility in Riyadh. Genome sequencing of MERS coronavirus from 6 cases demonstrated continued circulation of the recently described recombinant virus. A single unique frameshift deletion in open reading frame 5 was detected in the viral sequence from 1 case.",2016 Aug 3,"['Assiri, Abdullah M.', 'Biggs, Holly M.', 'Abedi, Glen R.', 'Lu, Xiaoyan', 'Bin Saeed, Abdulaziz', 'Abdalla, Osman', 'Mohammed, Mutaz', 'Al-Abdely, Hail M.', 'Algarni, Homoud S.', 'Alhakeem, Raafat F.', 'Almasri, Malak M.', 'Alsharef, Ali A.', 'Nooh, Randa', 'Erdman, Dean D.', 'Gerber, Susan I.', 'Watson, John T.']",Open Forum Infect Dis,,,True
de02275827ee3b513a51e620b7f040a6ee959d0b,PMC,A first step toward understanding patient safety,http://dx.doi.org/10.4097/kjae.2016.69.5.429,PMC5047977,27703622,CC BY-NC,"Patient safety has become an important policy agenda in healthcare systems since publication of the 1999 report entitled ""To Err Is Human."" The paradigm has changed from blaming the individual for the error to identifying the weakness in the system that led to the adverse events. Anesthesia is one of the first healthcare specialties to adopt techniques and lessons from the aviation industry. The widespread use of simulation programs and the application of human factors engineering to clinical practice are the influences of the aviation industry. Despite holding relatively advanced medical technology and comparable safety records, the Korean health industry has little understanding of the systems approach to patient safety. Because implementation of the existing system and program requires time, dedication, and financial support, the Korean healthcare industry is in urgent need of developing patient safety policies and putting them into practice to improve patient safety before it is too late.",2016 Oct 25,"Kim, Kyoung Ok",Korean J Anesthesiol,,,True
2024ea5609babbd8769ee9f1898e825306b49cfe,PMC,Production of specific IgY antibody to the recombinant FanC protein produced in Escherichia coli,,PMC5048125,27746871,CC BY-NC-SA,"OBJECTIVE(S): Enterotoxigenic Escherichia coli (ETEC) strains are one of the primary causes of diarrhea in newborn calves and in humans, pigs, and sheep. IgY technology has been identified as a promising alternative to generating a mass amount of specific antibody for use in immunotherapy and immunodiagnostics. The purpose of this study was to produce specific antibody by egg yolk antibody (IgY) to recombinant FanC protein from ETEC. MATERIALS AND METHODS: FanC (K99) gene was amplified from ETEC by specific primers and polymerase chain reaction. The gene was cloned and subcloned into pTZ57R/T and pET32a (+) vectors, respectively. Recombinant vector was transferred into E. coli BL21 CodonPlus (DE3). Protein expression was investigated by 1 mM IPTG induction. Hens were immunized by the purified recombinant FanC protein. The activity and specificity of the IgY antibody were detected by dot-blotting, Western blotting, and indirect ELISA. RESULTS: We obtained FanC specific IgYs by immunizing the hens with the recombinant FanC protein. The anti-FanC IgY showed binding specifically to the FanC protein of ETEC. CONCLUSION: The results emphasize that specific IgY against the recombinant FanC protein could be recommended as a candidate for passive immunization against ETEC infection in animals and humans.",2016 Aug,"['Nasiri, Khadijeh', 'Zibaee, Saeed', 'Nassiri, Mohammadreza', 'Tahmoorespur, Mojtaba', 'Haghparast, Alireza']",Iran J Basic Med Sci,,,True
8387ba520ac3172c8b428e5c95b6aad52d23d509,PMC,A Crimean-Congo hemorrhagic fever (CCHF) viral vaccine expressing nucleoprotein is immunogenic but fails to confer protection against lethal disease,http://dx.doi.org/10.1080/21645515.2015.1078045,PMC5049717,26309231,CC BY-NC,"Crimean-Congo Hemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. Between 15–70% of reported cases are fatal with no approved vaccine available. In the present study, the attenuated poxvirus vector, Modified Vaccinia virus Ankara, was used to develop a recombinant candidate vaccine expressing the CCHF virus nucleoprotein. Cellular and humoral immunogenicity was confirmed in 2 mouse strains, including type I interferon receptor knockout mice, which are susceptible to CCHF disease. Despite the immune responses generated post-immunisation, the vaccine failed to protect animals from lethal disease in a challenge model.",2015 Aug 26,"['Dowall, SD', 'Buttigieg, KR', 'Findlay-Wilson, SJD', 'Rayner, E', 'Pearson, G', 'Miloszewska, A', 'Graham, VA', 'Carroll, MW', 'Hewson, R']",Hum Vaccin Immunother,,,True
6c34a7324792c4d3594b3eae684933fb8ce4ca5a,PMC,Profile: International Vaccine Institute (IVI),http://dx.doi.org/10.1080/21645515.2015.1132687,PMC5049741,26766624,CC BY-NC,,2016 Jan 14,"Kim, Jerome H.",Hum Vaccin Immunother,,,False
662b7fe72aeb5beee387582742e087253b27201c,PMC,Ebola Virus Epidemiology and Evolution in Nigeria,http://dx.doi.org/10.1093/infdis/jiw190,PMC5050462,27377746,CC BY-NC-ND,"Containment limited the 2014 Nigerian Ebola virus (EBOV) disease outbreak to 20 reported cases and 8 fatalities. We present here clinical data and contact information for at least 19 case patients, and full-length EBOV genome sequences for 12 of the 20. The detailed contact data permits nearly complete reconstruction of the transmission tree for the outbreak. The EBOV genomic data are consistent with that tree. It confirms that there was a single source for the Nigerian infections, shows that the Nigerian EBOV lineage nests within a lineage previously seen in Liberia but is genetically distinct from it, and supports the conclusion that transmission from Nigeria to elsewhere did not occur.",2016 Oct 15,"['Folarin, Onikepe A.', 'Ehichioya, Deborah', 'Schaffner, Stephen F.', 'Winnicki, Sarah M.', 'Wohl, Shirlee', 'Eromon, Philomena', 'West, Kendra L.', 'Gladden-Young, Adrianne', 'Oyejide, Nicholas E.', 'Matranga, Christian B.', 'Deme, Awa Bineta', 'James, Ayorinde', 'Tomkins-Tinch, Christopher', 'Onyewurunwa, Kenneth', 'Ladner, Jason T.', 'Palacios, Gustavo', 'Nosamiefan, Iguosadolo', 'Andersen, Kristian G.', 'Omilabu, Sunday', 'Park, Daniel J.', 'Yozwiak, Nathan L.', 'Nasidi, Abdusallam', 'Garry, Robert F.', 'Tomori, Oyewale', 'Sabeti, Pardis C.', 'Happi, Christian T.']",J Infect Dis,,,True
cf6cd3c179962d45706d3c57967082c822626b71,PMC,Ebola Virus Epidemiology and Evolution in Nigeria,http://dx.doi.org/10.1093/infdis/jiw190,PMC5050462,27377746,CC BY-NC-ND,"Containment limited the 2014 Nigerian Ebola virus (EBOV) disease outbreak to 20 reported cases and 8 fatalities. We present here clinical data and contact information for at least 19 case patients, and full-length EBOV genome sequences for 12 of the 20. The detailed contact data permits nearly complete reconstruction of the transmission tree for the outbreak. The EBOV genomic data are consistent with that tree. It confirms that there was a single source for the Nigerian infections, shows that the Nigerian EBOV lineage nests within a lineage previously seen in Liberia but is genetically distinct from it, and supports the conclusion that transmission from Nigeria to elsewhere did not occur.",2016 Oct 15,"['Folarin, Onikepe A.', 'Ehichioya, Deborah', 'Schaffner, Stephen F.', 'Winnicki, Sarah M.', 'Wohl, Shirlee', 'Eromon, Philomena', 'West, Kendra L.', 'Gladden-Young, Adrianne', 'Oyejide, Nicholas E.', 'Matranga, Christian B.', 'Deme, Awa Bineta', 'James, Ayorinde', 'Tomkins-Tinch, Christopher', 'Onyewurunwa, Kenneth', 'Ladner, Jason T.', 'Palacios, Gustavo', 'Nosamiefan, Iguosadolo', 'Andersen, Kristian G.', 'Omilabu, Sunday', 'Park, Daniel J.', 'Yozwiak, Nathan L.', 'Nasidi, Abdusallam', 'Garry, Robert F.', 'Tomori, Oyewale', 'Sabeti, Pardis C.', 'Happi, Christian T.']",J Infect Dis,,,False
abf8ebc19a70435bb3185baff7a28478286fee92,PMC,Ebola Virus Epidemiology and Evolution in Nigeria,http://dx.doi.org/10.1093/infdis/jiw190,PMC5050462,27377746,CC BY-NC-ND,"Containment limited the 2014 Nigerian Ebola virus (EBOV) disease outbreak to 20 reported cases and 8 fatalities. We present here clinical data and contact information for at least 19 case patients, and full-length EBOV genome sequences for 12 of the 20. The detailed contact data permits nearly complete reconstruction of the transmission tree for the outbreak. The EBOV genomic data are consistent with that tree. It confirms that there was a single source for the Nigerian infections, shows that the Nigerian EBOV lineage nests within a lineage previously seen in Liberia but is genetically distinct from it, and supports the conclusion that transmission from Nigeria to elsewhere did not occur.",2016 Oct 15,"['Folarin, Onikepe A.', 'Ehichioya, Deborah', 'Schaffner, Stephen F.', 'Winnicki, Sarah M.', 'Wohl, Shirlee', 'Eromon, Philomena', 'West, Kendra L.', 'Gladden-Young, Adrianne', 'Oyejide, Nicholas E.', 'Matranga, Christian B.', 'Deme, Awa Bineta', 'James, Ayorinde', 'Tomkins-Tinch, Christopher', 'Onyewurunwa, Kenneth', 'Ladner, Jason T.', 'Palacios, Gustavo', 'Nosamiefan, Iguosadolo', 'Andersen, Kristian G.', 'Omilabu, Sunday', 'Park, Daniel J.', 'Yozwiak, Nathan L.', 'Nasidi, Abdusallam', 'Garry, Robert F.', 'Tomori, Oyewale', 'Sabeti, Pardis C.', 'Happi, Christian T.']",J Infect Dis,,,False
f0b95482306158df395281317e4f3f7b37c5a52c,PMC,Detection of respiratory viruses in shelter dogs maintained under varying environmental conditions,http://dx.doi.org/10.1016/j.bjm.2016.07.002,PMC5052379,27522932,CC BY-NC-ND,"Three dog shelters in Rio Grande do Sul were investigated for associations between the occurrence of respiratory viruses and shelter environmental conditions. Nasal secretions randomly collected during the cold season were tested via PCR, and this data collection was followed by nucleotide sequencing of the amplicons. In shelter #1 (poor sanitary and nutritional conditions, high animal density and constant contact between dogs), 78% (58/74) of the nasal samples were positive, 35% (26/74) of which were in single infections and 44% (32/74) of which were in coinfections. Shelters #2 and #3 had satisfactory sanitary and nutritional conditions, outdoors exercise areas (#2) and animal clustering by groups (#3). In shelter #2, 9% (3/35) of the samples were positive for Canine parainfluenza virus (CPIV), and 6% (2/35) were positive for Canid herpesvirus 1 (CaHV-1). In shelter #3, 9% (7/77) of the samples were positive for Canine adenovirus type 2 (CAdV-2), and 1% (1/77) were positive for Canine distemper virus (CDV). The amplicon sequences (CPIV and CDV nucleoprotein gene; CAdV-2 E3 gene; CaHV-1 glycoprotein B gene) showed 94–100% nucleotide identity with GenBank sequences. Our results demonstrate that CPIV, CAdV-2 and CDV are common in dog shelters and that their frequencies appear to be related with environmental and nutritional conditions. These results indicate the need for control/prevention measures, including vaccination and environmental management, to minimize these infections and improve dog health.",2016 Jul 19,"['Monteiro, Francielle Liz', 'Cargnelutti, Juliana Felipetto', 'Martins, Mathias', 'Anziliero, Deniz', 'Erhardt, Magnólia Martins', 'Weiblen, Rudi', 'Flores, Eduardo Furtado']",Braz J Microbiol,,,False
6566db587556ce7228eca39ac94dbf4a4b4dbd6c,PMC,"Ginseng, the natural effectual antiviral: Protective effects of Korean Red Ginseng against viral infection",http://dx.doi.org/10.1016/j.jgr.2015.09.002,PMC5052424,27746682,CC BY-NC-ND,"Korean Red Ginseng (KRG) is a heat-processed ginseng developed by the repeated steaming and air-drying of fresh ginseng. Compared with fresh ginseng, KRG has been shown to possess greater pharmacological activities and stability because of changes that occur in its chemical constituents during the steaming process. In addition to anticancer, anti-inflammatory, and immune-modulatory activities, KRG and its purified components have also been shown to possess protective effects against microbial infections. Here, we summarize the current knowledge on the properties of KRG and its components on infections with human pathogenic viruses such as respiratory syncytial virus, rhinovirus, influenza virus, human immunodeficiency virus, human herpes virus, hepatitis virus, norovirus, rotavirus, enterovirus, and coxsackievirus. Additionally, the therapeutic potential of KRG as an antiviral and vaccine adjuvant is discussed.",2016 Oct 16,"['Im, Kyungtaek', 'Kim, Jisu', 'Min, Hyeyoung']",J Ginseng Res,,,False
80dc6a5a5b823d6e1fb9802becae1575ddb8dd89,PMC,Contamination during doffing of personal protective equipment by healthcare providers,http://dx.doi.org/10.15441/ceem.15.019,PMC5052842,27752591,CC BY-NC,"OBJECTIVE: In this study, we aimed to describe the processes of both the donning and the doffing of personal protective equipment for Ebola and evaluate contamination during the doffing process. METHODS: We recruited study participants among physicians and nurses of the emergency department of Samsung Medical Center in Seoul, Korea. Participants were asked to carry out doffing and donning procedures with a helper after a 50-minute brief training and demonstration based on the 2014 Centers for Disease Control and Prevention protocol. Two separate cameras with high-density capability were set up, and the donning and doffing processes were video-taped. A trained examiner inspected all video recordings and coded for intervals, errors, and contaminations defined as the outside of the equipment touching the clinician’s body surface. RESULTS: Overall, 29 participants were enrolled. Twenty (68.9%) were female, and the mean age was 29.2 years. For the donning process, the average interval until the end was 234.2 seconds (standard deviation [SD], 65.7), and the most frequent errors occurred when putting on the outer gloves (27.5%), respirator (20.6%), and hood (20.6%). For the doffing process, the average interval until the end was 183.7 seconds (SD, 38.4), and the most frequent errors occurred during disinfecting the feet (37.9%), discarding the scrubs (17.2%), and putting on gloves (13.7%), respectively. During the doffing process, 65 incidences of contamination occurred (2.2 incidents/person). The most vulnerable processes were removing respirators (79.2%), removing the shoe covers (65.5%), and removal of the hood (41.3%). CONCLUSION: A significant number of contaminations occur during the doffing process of personal protective equipment.",2015 Sep 30,"['Lim, Seong Mi', 'Cha, Won Chul', 'Chae, Minjung Kathy', 'Jo, Ik Joon']",Clin Exp Emerg Med,,,True
80522e9ca5c69f759fcb3da6fcfdf3523891594e,PMC,Retrospective Multicenter Study of Respiratory Syncytial Virus Prophylaxis in Korean Children with Congenital Heart Diseases,http://dx.doi.org/10.4070/kcj.2016.46.5.719,PMC5054186,27721865,CC BY-NC,"BACKGROUND AND OBJECTIVES: We conducted a review of current data on respiratory syncytial virus (RSV) prophylaxis with palivizumab, in Korean children with congenital heart diseases (CHD). In 2009, the Korean guideline for RSV prophylaxis had established up to five shots monthly per RSV season, only for children <1 year of age with hemodynamic significance CHD (HS-CHD). SUBJECTS AND METHODS: During the RSV seasons in 2009-2015, we performed a retrospective review of data for 466 infants with CHD, examined at six centers in Korea. RESULTS: Infants received an average of 3.7±1.9 (range, 1-10) injections during the RSV season. Fifty-seven HS-CHD patients (12.2%) were hospitalized with breakthrough RSV bronchiolitis, with a recurrence in three patients, one year after the initial check-up. Among patients with simple CHD, only five (1.1%) patients received one additional dose postoperatively, as per the limitations set by the Korean guideline. Among the 30 deaths (6.4%), five (1.1%) were attributed to RSV infection; three to simple CHD, one to Tetralogy of Fallot, and one to hypertrophic cardiomyopathy (HCM). Of the three HCM patients that exceeded guidelines for RSV prophylaxis, two (66.6%) were hospitalized, and one died of RSV infection (33.3%). CONCLUSION: In accordance to the Korean guideline, minimal injections of palivizumab were administered to patients having HS-CHD <one year of age during the RSV season; the risk of RSV infection remains significant among children with simple CHD, cardiomyopathy, and children above the age of one year with HS-CHD.",2016 Sep 28,"['Kim, Ah Young', 'Jung, Se Yong', 'Choi, Jae Young', 'Kim, Gi Beom', 'Kim, Young-Hwue', 'Shim, Woo Sup', 'Kang, I-Seok', 'Jung, Jo Won']",Korean Circ J,,,True
ce53771489f0701f2753a2bb49c861c5f73bc461,PMC,Jackknife and Bootstrap Tests of the Composition Vector Trees,http://dx.doi.org/10.1016/S1672-0229(10)60028-9,PMC5054193,21382595,CC BY-NC-SA,"Composition vector trees (CVTrees) are inferred from whole-genome data by an alignment-free and parameter-free method. The agreement of these trees with the corresponding taxonomy provides an objective justification of the inferred phylogeny. In this work, we show the stability and self-consistency of CVTrees by performing bootstrap and jackknife re-sampling tests adapted to this alignment-free approach. Our ultimate goal is to advocate the viewpoint that time-consuming statistical re-sampling tests can be avoided at all in using this alignment-free approach. Agreement with taxonomy should be taken as a major criterion to estimate prokaryotic phylogenetic trees.",2010 Dec 5,"['Zuo, Guanghong', 'Xu, Zhao', 'Yu, Hongjie', 'Hao, Bailin']",Genomics Proteomics Bioinformatics,,,False
06c4f9daabdf5ee16fb4b581a954e3909d9f17a0,PMC,"Computational Analysis of Cysteine Proteases (Clan CA, Family C1) of Leishmania major to Find Potential Epitopic Regions",http://dx.doi.org/10.1016/S1672-0229(08)60037-6,PMC5054412,19944381,CC BY-NC-SA,"Leishmania is associated with a broad spectrum of diseases, ranging from simple cutaneous to invasive visceral leishmaniasis. Here, the sequences of ten cysteine proteases of types A, B and C of Leishmania major were obtained from GeneDB database. Prediction of MHC class I epitopes of these cysteine proteases was performed by NetCTL program version 1.2. In addition, by using BcePred server, different structural properties of the proteins were predicted to find out their potential B cell epitopes. According to this computational analysis, nine regions were predicted as B cell epitopes. The results provide useful information for designing peptide-based vaccines.",2009 Sep 25,"['Saffari, Babak', 'Mohabatkar, Hassan']",Genomics Proteomics Bioinformatics,,,False
357496f6d93f95b8c286882be6bd219ff79f90e1,PMC,Poster presentations,,PMC5054515,,CC BY-NC,,,,J Virus Erad.; 2(Suppl 1):21-52,,,True
4e14a0bdb3702f1c98145da4335c327a99b7275c,PMC,Clinical Progression and Cytokine Profiles of Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.3346/jkms.2016.31.11.1717,PMC5056202,27709848,CC BY-NC,"Clinical progression over time and cytokine profiles have not been well defined in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. We included 17 patients with laboratory-confirmed MERS-CoV during the 2015 outbreak in Korea. Clinical and laboratory parameters were collected prospectively. Serum cytokine and chemokine levels in serial serum samples were measured using enzyme-linked immunosorbent assay. All patients presented with fever. The median time to defervescence was 18 days. Nine patients required oxygen supplementation and classified into severe group. In the severe group, chest infiltrates suddenly began to worsen around day 7 of illness, and dyspnea developed at the end of the first week and became apparent in the second week. Median time from symptom onset to oxygen supplementation was 8 days. The severe group had higher neutrophil counts during week 1 than the mild group (4,500 vs. 2,200/µL, P = 0.026). In the second week of illness, the severe group had higher serum levels of IL-6 (54 vs. 4 pg/mL, P = 0.006) and CXCL-10 (2,642 vs. 382 pg/mL, P < 0.001). IFN-α response was not observed in mild cases. Our data shows that clinical condition may suddenly deteriorate around 7 days of illness and the serum levels of IL-6 and CXCL-10 was significantly elevated in MERS-CoV patients who developed severe diseases.",2016 Nov 2,"['Kim, Eu Suk', 'Choe, Pyoeng Gyun', 'Park, Wan Beom', 'Oh, Hong Sang', 'Kim, Eun Jung', 'Nam, Eun Young', 'Na, Sun Hee', 'Kim, Moonsuk', 'Song, Kyoung-Ho', 'Bang, Ji Hwan', 'Park, Sang Won', 'Kim, Hong Bin', 'Kim, Nam Joong', 'Oh, Myoung-don']",J Korean Med Sci,,,True
45448178ffe1a3c7ed79771a4d760b1e056c2f2f,PMC,Clinical Progression and Cytokine Profiles of Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.3346/jkms.2016.31.11.1717,PMC5056202,27709848,CC BY-NC,"Clinical progression over time and cytokine profiles have not been well defined in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. We included 17 patients with laboratory-confirmed MERS-CoV during the 2015 outbreak in Korea. Clinical and laboratory parameters were collected prospectively. Serum cytokine and chemokine levels in serial serum samples were measured using enzyme-linked immunosorbent assay. All patients presented with fever. The median time to defervescence was 18 days. Nine patients required oxygen supplementation and classified into severe group. In the severe group, chest infiltrates suddenly began to worsen around day 7 of illness, and dyspnea developed at the end of the first week and became apparent in the second week. Median time from symptom onset to oxygen supplementation was 8 days. The severe group had higher neutrophil counts during week 1 than the mild group (4,500 vs. 2,200/µL, P = 0.026). In the second week of illness, the severe group had higher serum levels of IL-6 (54 vs. 4 pg/mL, P = 0.006) and CXCL-10 (2,642 vs. 382 pg/mL, P < 0.001). IFN-α response was not observed in mild cases. Our data shows that clinical condition may suddenly deteriorate around 7 days of illness and the serum levels of IL-6 and CXCL-10 was significantly elevated in MERS-CoV patients who developed severe diseases.",2016 Nov 2,"['Kim, Eu Suk', 'Choe, Pyoeng Gyun', 'Park, Wan Beom', 'Oh, Hong Sang', 'Kim, Eun Jung', 'Nam, Eun Young', 'Na, Sun Hee', 'Kim, Moonsuk', 'Song, Kyoung-Ho', 'Bang, Ji Hwan', 'Park, Sang Won', 'Kim, Hong Bin', 'Kim, Nam Joong', 'Oh, Myoung-don']",J Korean Med Sci,,,False
8c6655b3fb2c390e1045ebb47a9b5d337a5f1ab0,PMC,Clinical Progression and Cytokine Profiles of Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.3346/jkms.2016.31.11.1717,PMC5056202,27709848,CC BY-NC,"Clinical progression over time and cytokine profiles have not been well defined in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. We included 17 patients with laboratory-confirmed MERS-CoV during the 2015 outbreak in Korea. Clinical and laboratory parameters were collected prospectively. Serum cytokine and chemokine levels in serial serum samples were measured using enzyme-linked immunosorbent assay. All patients presented with fever. The median time to defervescence was 18 days. Nine patients required oxygen supplementation and classified into severe group. In the severe group, chest infiltrates suddenly began to worsen around day 7 of illness, and dyspnea developed at the end of the first week and became apparent in the second week. Median time from symptom onset to oxygen supplementation was 8 days. The severe group had higher neutrophil counts during week 1 than the mild group (4,500 vs. 2,200/µL, P = 0.026). In the second week of illness, the severe group had higher serum levels of IL-6 (54 vs. 4 pg/mL, P = 0.006) and CXCL-10 (2,642 vs. 382 pg/mL, P < 0.001). IFN-α response was not observed in mild cases. Our data shows that clinical condition may suddenly deteriorate around 7 days of illness and the serum levels of IL-6 and CXCL-10 was significantly elevated in MERS-CoV patients who developed severe diseases.",2016 Nov 2,"['Kim, Eu Suk', 'Choe, Pyoeng Gyun', 'Park, Wan Beom', 'Oh, Hong Sang', 'Kim, Eun Jung', 'Nam, Eun Young', 'Na, Sun Hee', 'Kim, Moonsuk', 'Song, Kyoung-Ho', 'Bang, Ji Hwan', 'Park, Sang Won', 'Kim, Hong Bin', 'Kim, Nam Joong', 'Oh, Myoung-don']",J Korean Med Sci,,,False
1af6e74e304a0139ad8a4c45e1b999d860e2776d,PMC,Clinical Progression and Cytokine Profiles of Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.3346/jkms.2016.31.11.1717,PMC5056202,27709848,CC BY-NC,"Clinical progression over time and cytokine profiles have not been well defined in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. We included 17 patients with laboratory-confirmed MERS-CoV during the 2015 outbreak in Korea. Clinical and laboratory parameters were collected prospectively. Serum cytokine and chemokine levels in serial serum samples were measured using enzyme-linked immunosorbent assay. All patients presented with fever. The median time to defervescence was 18 days. Nine patients required oxygen supplementation and classified into severe group. In the severe group, chest infiltrates suddenly began to worsen around day 7 of illness, and dyspnea developed at the end of the first week and became apparent in the second week. Median time from symptom onset to oxygen supplementation was 8 days. The severe group had higher neutrophil counts during week 1 than the mild group (4,500 vs. 2,200/µL, P = 0.026). In the second week of illness, the severe group had higher serum levels of IL-6 (54 vs. 4 pg/mL, P = 0.006) and CXCL-10 (2,642 vs. 382 pg/mL, P < 0.001). IFN-α response was not observed in mild cases. Our data shows that clinical condition may suddenly deteriorate around 7 days of illness and the serum levels of IL-6 and CXCL-10 was significantly elevated in MERS-CoV patients who developed severe diseases.",2016 Nov 2,"['Kim, Eu Suk', 'Choe, Pyoeng Gyun', 'Park, Wan Beom', 'Oh, Hong Sang', 'Kim, Eun Jung', 'Nam, Eun Young', 'Na, Sun Hee', 'Kim, Moonsuk', 'Song, Kyoung-Ho', 'Bang, Ji Hwan', 'Park, Sang Won', 'Kim, Hong Bin', 'Kim, Nam Joong', 'Oh, Myoung-don']",J Korean Med Sci,,,False
b9abef997734bb82ed611b4ae90c70eb3dc12e5b,PMC,Clinical Progression and Cytokine Profiles of Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.3346/jkms.2016.31.11.1717,PMC5056202,27709848,CC BY-NC,"Clinical progression over time and cytokine profiles have not been well defined in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. We included 17 patients with laboratory-confirmed MERS-CoV during the 2015 outbreak in Korea. Clinical and laboratory parameters were collected prospectively. Serum cytokine and chemokine levels in serial serum samples were measured using enzyme-linked immunosorbent assay. All patients presented with fever. The median time to defervescence was 18 days. Nine patients required oxygen supplementation and classified into severe group. In the severe group, chest infiltrates suddenly began to worsen around day 7 of illness, and dyspnea developed at the end of the first week and became apparent in the second week. Median time from symptom onset to oxygen supplementation was 8 days. The severe group had higher neutrophil counts during week 1 than the mild group (4,500 vs. 2,200/µL, P = 0.026). In the second week of illness, the severe group had higher serum levels of IL-6 (54 vs. 4 pg/mL, P = 0.006) and CXCL-10 (2,642 vs. 382 pg/mL, P < 0.001). IFN-α response was not observed in mild cases. Our data shows that clinical condition may suddenly deteriorate around 7 days of illness and the serum levels of IL-6 and CXCL-10 was significantly elevated in MERS-CoV patients who developed severe diseases.",2016 Nov 2,"['Kim, Eu Suk', 'Choe, Pyoeng Gyun', 'Park, Wan Beom', 'Oh, Hong Sang', 'Kim, Eun Jung', 'Nam, Eun Young', 'Na, Sun Hee', 'Kim, Moonsuk', 'Song, Kyoung-Ho', 'Bang, Ji Hwan', 'Park, Sang Won', 'Kim, Hong Bin', 'Kim, Nam Joong', 'Oh, Myoung-don']",J Korean Med Sci,,,False
862a11c41a472e160babf44f26b8fa3185111739,PMC,Clinical Progression and Cytokine Profiles of Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.3346/jkms.2016.31.11.1717,PMC5056202,27709848,CC BY-NC,"Clinical progression over time and cytokine profiles have not been well defined in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. We included 17 patients with laboratory-confirmed MERS-CoV during the 2015 outbreak in Korea. Clinical and laboratory parameters were collected prospectively. Serum cytokine and chemokine levels in serial serum samples were measured using enzyme-linked immunosorbent assay. All patients presented with fever. The median time to defervescence was 18 days. Nine patients required oxygen supplementation and classified into severe group. In the severe group, chest infiltrates suddenly began to worsen around day 7 of illness, and dyspnea developed at the end of the first week and became apparent in the second week. Median time from symptom onset to oxygen supplementation was 8 days. The severe group had higher neutrophil counts during week 1 than the mild group (4,500 vs. 2,200/µL, P = 0.026). In the second week of illness, the severe group had higher serum levels of IL-6 (54 vs. 4 pg/mL, P = 0.006) and CXCL-10 (2,642 vs. 382 pg/mL, P < 0.001). IFN-α response was not observed in mild cases. Our data shows that clinical condition may suddenly deteriorate around 7 days of illness and the serum levels of IL-6 and CXCL-10 was significantly elevated in MERS-CoV patients who developed severe diseases.",2016 Nov 2,"['Kim, Eu Suk', 'Choe, Pyoeng Gyun', 'Park, Wan Beom', 'Oh, Hong Sang', 'Kim, Eun Jung', 'Nam, Eun Young', 'Na, Sun Hee', 'Kim, Moonsuk', 'Song, Kyoung-Ho', 'Bang, Ji Hwan', 'Park, Sang Won', 'Kim, Hong Bin', 'Kim, Nam Joong', 'Oh, Myoung-don']",J Korean Med Sci,,,False
bd3c61dc21c0945cdc0d62d967f4b24ee2eae648,PMC,Clinical Progression and Cytokine Profiles of Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.3346/jkms.2016.31.11.1717,PMC5056202,27709848,CC BY-NC,"Clinical progression over time and cytokine profiles have not been well defined in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. We included 17 patients with laboratory-confirmed MERS-CoV during the 2015 outbreak in Korea. Clinical and laboratory parameters were collected prospectively. Serum cytokine and chemokine levels in serial serum samples were measured using enzyme-linked immunosorbent assay. All patients presented with fever. The median time to defervescence was 18 days. Nine patients required oxygen supplementation and classified into severe group. In the severe group, chest infiltrates suddenly began to worsen around day 7 of illness, and dyspnea developed at the end of the first week and became apparent in the second week. Median time from symptom onset to oxygen supplementation was 8 days. The severe group had higher neutrophil counts during week 1 than the mild group (4,500 vs. 2,200/µL, P = 0.026). In the second week of illness, the severe group had higher serum levels of IL-6 (54 vs. 4 pg/mL, P = 0.006) and CXCL-10 (2,642 vs. 382 pg/mL, P < 0.001). IFN-α response was not observed in mild cases. Our data shows that clinical condition may suddenly deteriorate around 7 days of illness and the serum levels of IL-6 and CXCL-10 was significantly elevated in MERS-CoV patients who developed severe diseases.",2016 Nov 2,"['Kim, Eu Suk', 'Choe, Pyoeng Gyun', 'Park, Wan Beom', 'Oh, Hong Sang', 'Kim, Eun Jung', 'Nam, Eun Young', 'Na, Sun Hee', 'Kim, Moonsuk', 'Song, Kyoung-Ho', 'Bang, Ji Hwan', 'Park, Sang Won', 'Kim, Hong Bin', 'Kim, Nam Joong', 'Oh, Myoung-don']",J Korean Med Sci,,,False
6ff336c5f099acbe84cf7cfe5f68bd5ba672d6b8,PMC,Impact of a porcine epidemic diarrhea outbreak on swine productivity in Japan: a retrospective cohort study,http://dx.doi.org/10.1292/jvms.15-0723,PMC5059364,27170488,CC BY-NC-ND,"The objective was to investigate porcine epidemic diarrhea (PED) outbreak that occurred in 2014 in Japan and its effects on herd-level productivity using a data recording system (PigINFO). The study herds were selected from farrow-to-finish herds (n=99) that entered in the PigINFO system between July 2013 and March 2015. From 1 April to 30 June 2014 (PED epidemic), any herds with clinical signs of PED and feces positive for porcine epidemic diarrhea virus (PEDV) on polymerase chain reaction analysis and/or immunohistochemical staining were defined as PED-positive (n=38). They were further classified into those with long PED periods (L-PED-positive; n=28) and those with short PED periods (S-PED-positive; n=10). Herds with no clinical signs of PED were classified as PED-negative (n=61). Herd-level production data, including preweaning mortality (%; PRWM), postweaning mortality (%; POWM), pigs weaned per litter (PWL), pigs born alive per litter, litters per mated female per year and pigs marketed per sow (MP), were calculated every 3 months during study period. During the PED epidemic, L-PED-positive herds had significantly higher PRWM and POWM than PED-negative herds, and L-PED-positive and S-PED-positive herds had significantly lower PWL. During October–December 2014, L-PED-positive herds had significantly fewer MP than PED-negative herds. The PED outbreak increased mortality and consequently reduced the numbers of marketed pigs. The rapid control of an outbreak is important for reducing the financial losses arising from PED infections.",2016 Sep 12,"['YAMANE, Itsuro', 'YAMAZAKI, Hisanori', 'ISHIZEKI, Sayoko', 'WATANABE, Yugo', 'OKUMURA, Hanako', 'OKUBO, Mitsuharu', 'KURE, Katsumasa', 'HAYAKAWA, Yuiko', 'FURUKAWA, Makoto', 'OOI, Munetaka', 'MIZUKAMI, Yoshihiro', 'ITO, Mitsugu']",J Vet Med Sci,,,True
f6cb05b1b2874e3aabdc66876575cda7d7477d31,PMC,Development of a mouse-feline chimeric antibody against feline tumor necrosis factor-alpha,http://dx.doi.org/10.1292/jvms.16-0020,PMC5059372,27264736,CC BY-NC-ND,"Feline infectious peritonitis (FIP) is a fatal inflammatory disease caused by FIP virus infection. Feline tumor necrosis factor (fTNF)-alpha is closely involved in the aggravation of FIP pathology. We previously described the preparation of neutralizing mouse anti-fTNF-alpha monoclonal antibody (mAb 2–4) and clarified its role in the clinical condition of cats with FIP using in vitro systems. However, administration of mouse mAb 2–4 to cat may lead to a production of feline anti-mouse antibodies. In the present study, we prepared a mouse-feline chimeric mAb (chimeric mAb 2–4) by fusing the variable region of mouse mAb 2–4 to the constant region of feline antibody. The chimeric mAb 2–4 was confirmed to have fTNF-alpha neutralization activity. Purified mouse mAb 2–4 and chimeric mAb 2–4 were repeatedly administered to cats, and the changes in the ability to induce feline anti-mouse antibody response were investigated. In the serum of cats treated with mouse mAb 2–4, feline anti-mouse antibody production was induced, and the fTNF-alpha neutralization effect of mouse mAb 2–4 was reduced. In contrast, in cats treated with chimeric mAb 2–4, the feline anti-mouse antibody response was decreased compared to that of mouse mAb 2–4-treated cats.",2016 Sep 4,"['DOKI, Tomoyoshi', 'TAKANO, Tomomi', 'HOHDATSU, Tsutomu']",J Vet Med Sci,,,True
e95912dc0ea265d0559e79f33c0c9c9fb1834b6a,PMC,Development of a mouse-feline chimeric antibody against feline tumor necrosis factor-alpha,http://dx.doi.org/10.1292/jvms.16-0020,PMC5059372,27264736,CC BY-NC-ND,"Feline infectious peritonitis (FIP) is a fatal inflammatory disease caused by FIP virus infection. Feline tumor necrosis factor (fTNF)-alpha is closely involved in the aggravation of FIP pathology. We previously described the preparation of neutralizing mouse anti-fTNF-alpha monoclonal antibody (mAb 2–4) and clarified its role in the clinical condition of cats with FIP using in vitro systems. However, administration of mouse mAb 2–4 to cat may lead to a production of feline anti-mouse antibodies. In the present study, we prepared a mouse-feline chimeric mAb (chimeric mAb 2–4) by fusing the variable region of mouse mAb 2–4 to the constant region of feline antibody. The chimeric mAb 2–4 was confirmed to have fTNF-alpha neutralization activity. Purified mouse mAb 2–4 and chimeric mAb 2–4 were repeatedly administered to cats, and the changes in the ability to induce feline anti-mouse antibody response were investigated. In the serum of cats treated with mouse mAb 2–4, feline anti-mouse antibody production was induced, and the fTNF-alpha neutralization effect of mouse mAb 2–4 was reduced. In contrast, in cats treated with chimeric mAb 2–4, the feline anti-mouse antibody response was decreased compared to that of mouse mAb 2–4-treated cats.",2016 Sep 4,"['DOKI, Tomoyoshi', 'TAKANO, Tomomi', 'HOHDATSU, Tsutomu']",J Vet Med Sci,,,False
b6afd6aa34818636e4b69364980971be64bad8e2,PMC,Rational design of a synthetic mammalian riboswitch as a ligand-responsive -1 ribosomal frame-shifting stimulator,http://dx.doi.org/10.1093/nar/gkw718,PMC5062990,27521370,CC BY-NC,"Metabolite-responsive RNA pseudoknots derived from prokaryotic riboswitches have been shown to stimulate −1 programmed ribosomal frameshifting (PRF), suggesting −1 PRF as a promising gene expression platform to extend riboswitch applications in higher eukaryotes. However, its general application has been hampered by difficulty in identifying a specific ligand-responsive pseudoknot that also functions as a ligand-dependent -1 PRF stimulator. We addressed this problem by using the −1 PRF stimulation pseudoknot of SARS-CoV (SARS-PK) to build a ligand-dependent −1 PRF stimulator. In particular, the extra stem of SARS-PK was replaced by an RNA aptamer of theophylline and designed to couple theophylline binding with the stimulation of −1 PRF. Conformational and functional analyses indicate that the engineered theophylline-responsive RNA functions as a mammalian riboswitch with robust theophylline-dependent −1 PRF stimulation activity in a stable human 293T cell-line. Thus, RNA–ligand interaction repertoire provided by in vitro selection becomes accessible to ligand-specific −1 PRF stimulator engineering using SARS-PK as the scaffold for synthetic biology application.",2016 Oct 14,"['Lin, Ya-Hui', 'Chang, Kung-Yao']",Nucleic Acids Res,,,True
ddc19cc505bedd6fc059d96d6b5a7c4ff647b164,PMC,Rational design of a synthetic mammalian riboswitch as a ligand-responsive -1 ribosomal frame-shifting stimulator,http://dx.doi.org/10.1093/nar/gkw718,PMC5062990,27521370,CC BY-NC,"Metabolite-responsive RNA pseudoknots derived from prokaryotic riboswitches have been shown to stimulate −1 programmed ribosomal frameshifting (PRF), suggesting −1 PRF as a promising gene expression platform to extend riboswitch applications in higher eukaryotes. However, its general application has been hampered by difficulty in identifying a specific ligand-responsive pseudoknot that also functions as a ligand-dependent -1 PRF stimulator. We addressed this problem by using the −1 PRF stimulation pseudoknot of SARS-CoV (SARS-PK) to build a ligand-dependent −1 PRF stimulator. In particular, the extra stem of SARS-PK was replaced by an RNA aptamer of theophylline and designed to couple theophylline binding with the stimulation of −1 PRF. Conformational and functional analyses indicate that the engineered theophylline-responsive RNA functions as a mammalian riboswitch with robust theophylline-dependent −1 PRF stimulation activity in a stable human 293T cell-line. Thus, RNA–ligand interaction repertoire provided by in vitro selection becomes accessible to ligand-specific −1 PRF stimulator engineering using SARS-PK as the scaffold for synthetic biology application.",2016 Oct 14,"['Lin, Ya-Hui', 'Chang, Kung-Yao']",Nucleic Acids Res,,,False
69ec8583af7713749c3c85d5a3eb5e506196150b,PMC,Complement pathway amplifies caspase-11–dependent cell death and endotoxin-induced sepsis severity,http://dx.doi.org/10.1084/jem.20160027,PMC5068231,27697835,CC BY-NC-SA,"Cell death and release of proinflammatory mediators contribute to mortality during sepsis. Specifically, caspase-11–dependent cell death contributes to pathology and decreases in survival time in sepsis models. Priming of the host cell, through TLR4 and interferon receptors, induces caspase-11 expression, and cytosolic LPS directly stimulates caspase-11 activation, promoting the release of proinflammatory cytokines through pyroptosis and caspase-1 activation. Using a CRISPR-Cas9–mediated genome-wide screen, we identified novel mediators of caspase-11–dependent cell death. We found a complement-related peptidase, carboxypeptidase B1 (Cpb1), to be required for caspase-11 gene expression and subsequent caspase-11–dependent cell death. Cpb1 modifies a cleavage product of C3, which binds to and activates C3aR, and then modulates innate immune signaling. We find the Cpb1–C3–C3aR pathway induces caspase-11 expression through amplification of MAPK activity downstream of TLR4 and Ifnar activation, and mediates severity of LPS-induced sepsis (endotoxemia) and disease outcome in mice. We show C3aR is required for up-regulation of caspase-11 orthologues, caspase-4 and -5, in primary human macrophages during inflammation and that c3aR1 and caspase-5 transcripts are highly expressed in patients with severe sepsis; thus, suggesting that these pathways are important in human sepsis. Our results highlight a novel role for complement and the Cpb1–C3–C3aR pathway in proinflammatory signaling, caspase-11 cell death, and sepsis severity.",2016 Oct 17,"['Napier, Brooke A.', 'Brubaker, Sky W.', 'Sweeney, Timothy E.', 'Monette, Patrick', 'Rothmeier, Greggory H.', 'Gertsvolf, Nina A.', 'Puschnik, Andreas', 'Carette, Jan E.', 'Khatri, Purvesh', 'Monack, Denise M.']",J Exp Med,,,True
5f52ac4738312fdb215ad06e5a2e886a6fb63efd,PMC,Complement pathway amplifies caspase-11–dependent cell death and endotoxin-induced sepsis severity,http://dx.doi.org/10.1084/jem.20160027,PMC5068231,27697835,CC BY-NC-SA,"Cell death and release of proinflammatory mediators contribute to mortality during sepsis. Specifically, caspase-11–dependent cell death contributes to pathology and decreases in survival time in sepsis models. Priming of the host cell, through TLR4 and interferon receptors, induces caspase-11 expression, and cytosolic LPS directly stimulates caspase-11 activation, promoting the release of proinflammatory cytokines through pyroptosis and caspase-1 activation. Using a CRISPR-Cas9–mediated genome-wide screen, we identified novel mediators of caspase-11–dependent cell death. We found a complement-related peptidase, carboxypeptidase B1 (Cpb1), to be required for caspase-11 gene expression and subsequent caspase-11–dependent cell death. Cpb1 modifies a cleavage product of C3, which binds to and activates C3aR, and then modulates innate immune signaling. We find the Cpb1–C3–C3aR pathway induces caspase-11 expression through amplification of MAPK activity downstream of TLR4 and Ifnar activation, and mediates severity of LPS-induced sepsis (endotoxemia) and disease outcome in mice. We show C3aR is required for up-regulation of caspase-11 orthologues, caspase-4 and -5, in primary human macrophages during inflammation and that c3aR1 and caspase-5 transcripts are highly expressed in patients with severe sepsis; thus, suggesting that these pathways are important in human sepsis. Our results highlight a novel role for complement and the Cpb1–C3–C3aR pathway in proinflammatory signaling, caspase-11 cell death, and sepsis severity.",2016 Oct 17,"['Napier, Brooke A.', 'Brubaker, Sky W.', 'Sweeney, Timothy E.', 'Monette, Patrick', 'Rothmeier, Greggory H.', 'Gertsvolf, Nina A.', 'Puschnik, Andreas', 'Carette, Jan E.', 'Khatri, Purvesh', 'Monack, Denise M.']",J Exp Med,,,True
cb62f467ee641118d0b7d0b6244c6f7aa800416f,PMC,Roles of N‐Myc and STAT interactor in cancer: From initiation to dissemination,http://dx.doi.org/10.1002/ijc.30043,PMC5069610,26874464,CC BY-NC-ND,"N‐myc & STAT Interactor, NMI, is a protein that has mostly been studied for its physical interactions with transcription factors that play critical roles in tumor growth, progression and metastasis. NMI is an inducible protein, thus its intracellular levels and location can vary dramatically, influencing a diverse array of cellular functions in a context‐dependent manner. The physical interactions of NMI with its binding partners have been linked to many aspects of tumor biology including DNA damage response, cell death, epithelial‐to‐mesenchymal transition and stemness. Thus, discovering more details about the function(s) of NMI could reveal key insights into how transcription factors like c‐Myc, STATs and BRCA1 are contextually regulated. Although a normal, physiological function of NMI has not yet been discovered, it has potential roles in pathologies ranging from viral infection to cancer. This review provides a timely perspective of the unfolding roles of NMI with specific focus on cancer progression and metastasis.",2016 Aug 1,"['Pruitt, Hawley C.', 'Devine, Daniel J.', 'Samant, Rajeev S.']",Int J Cancer,,,True
28698e9d58d0b455cfa1adb28be25bc7f9286859,PMC,Chloroquine could be used for the treatment of filoviral infections and other viral infections that emerge or emerged from viruses requiring an acidic pH for infectivity,http://dx.doi.org/10.1002/cbf.3182,PMC5071688,27001679,CC BY-NC,"Viruses from the Filoviridae family, as many other virus families, require an acidic pH for successful infection and are therefore susceptible to the actions of 4‐aminoquinolines, such as chloroquine. Although the mechanisms of action of chloroquine clearly indicate that it might inhibit filoviral infections, several clinical trials that attempted to use chloroquine in the treatment of other acute viral infections – including dengue and influenza A and B – caused by low pH‐dependent viruses, have reported that chloroquine had no clinical efficacy, and these results demoted chloroquine from the potential treatments for other virus families requiring low pH for infectivity. The present review is aimed at investigating whether chloroquine could combat the present Ebola virus epidemic, and also at exploring the main reasons for the reported lack of efficacy. Literature was sourced from PubMed, Scopus, Google Scholar, reference list of articles and textbooks – Fields Virology (Volumes 1and 2), the cytokine handbook, Pharmacology in Medicine: Principles and Practice, and hydroxychloroquine and chloroquine retinopathy. The present analysis concludes that (1) chloroquine might find a place in the treatment of Ebola, either as a monotherapy or in combination therapies; (2) the ineffectiveness of chloroquine, or its analogue, hydroxychloroquine, at treating infections from low pH‐dependent viruses is a result of the failure to attain and sustain a steady state concentration sufficient to increase and keep the pH of the acidic organelles to approximately neutral levels; (3) to successfully treat filoviral infections – or other viral infections that emerge or emerged from low pH‐dependent viruses – a steady state chloroquine plasma concentration of at least 1 µg/mL(~3.125 μM/L) or a whole blood concentration of 16 μM/L must be achieved and be sustained until the patients' viraemia becomes undetectable. These concentrations, however, do not rule out the efficacy of other, higher, steady state concentrations – although such concentrations might be accompanied by severe adverse effects or toxicities. The feasibility of the conclusion in the preceding texts has recently been supported by a subsequent study that shows that amodiaquine, a derivative of CQ, is able to protect humans infected with Ebola from death.",2016 Jun 21,"Akpovwa, Hephzibah",Cell Biochem Funct,,,True
50a6717377c416aadc6204e0e92f96d12ab4b0e7,PMC,Inhibitor-Based Therapeutics for Treatment of Viral Hepatitis,http://dx.doi.org/10.14218/JCTH.2016.00025,PMC5075008,27777893,CC BY-NC,"Viral hepatitis remains a significant worldwide threat, in spite of the availability of several successful therapeutic and vaccination strategies. Complications associated with acute and chronic infections, such as liver failure, cirrhosis and hepatocellular carcinoma, are the cause of considerable morbidity and mortality. Given the significant burden on the healthcare system caused by viral hepatitis, it is essential that novel, more effective therapeutics be developed. The present review attempts to summarize the current treatments against viral hepatitis, and provides an outline for upcoming, promising new therapeutics. Development of novel therapeutics requires an understanding of the viral life cycles and viral effectors in molecular detail. As such, this review also discusses virally-encoded effectors, found to be essential for virus survival and replication in the host milieu, which may be utilized as potential candidates for development of alternative therapies in the future.",2016 Sep 28,"['Dey, Debajit', 'Banerjee, Manidipa']",J Clin Transl Hepatol,,,True
046b480f92a27f809d67c98c77752037f3342d2a,PMC,Human bocavirus: Current knowledge and future challenges,http://dx.doi.org/10.3748/wjg.v22.i39.8684,PMC5075545,27818586,CC BY-NC,"Human bocavirus (HBoV) is a parvovirus isolated about a decade ago and found worldwide in both respiratory samples, mainly from early life and children of 6-24 mo of age with acute respiratory infection, and in stool samples, from patients with gastroenteritis. Since then, other viruses related to the first HBoV isolate (HBoV1), namely HBoV2, HBoV3 and HBoV4, have been detected principally in human faeces. HBoVs are small non-enveloped single-stranded DNA viruses of about 5300 nucleotides, consisting of three open reading frames encoding the first two the non-structural protein 1 (NS1) and nuclear phosphoprotein (NP1) and the third the viral capsid proteins 1 and 2 (VP1 and VP2). HBoV pathogenicity remains to be fully clarified mainly due to the lack of animal models for the difficulties in replicating the virus in in vitro cell cultures, and the fact that HBoV infection is frequently accompanied by at least another viral and/or bacterial respiratory and/or gastroenteric pathogen infection. Current diagnostic methods to support HBoV detection include polymerase chain reaction, real-time PCR, enzyme-linked immunosorbent assay and enzyme immunoassay using recombinant VP2 or virus-like particle capsid proteins, although sequence-independent amplification techniques combined with next-generation sequencing platforms promise rapid and simultaneous detection of the pathogens in the future. This review presents the current knowledge on HBoV genotypes with emphasis on taxonomy, phylogenetic relationship and genomic analysis, biology, epidemiology, pathogenesis and diagnostic methods. The emerging discussion on HBoVs as true pathogen or innocent bystander is also emphasized.",2016 Oct 21,"['Guido, Marcello', 'Tumolo, Maria Rosaria', 'Verri, Tiziano', 'Romano, Alessandro', 'Serio, Francesca', 'De Giorgi, Mattia', 'De Donno, Antonella', 'Bagordo, Francesco', 'Zizza, Antonella']",World J Gastroenterol,,,True
b8cd20475a12eda90f29fcf38b449c086e703144,PMC,Disability-Adjusted Life Years for Communicable Disease in the Korean Burden of Disease Study 2012,http://dx.doi.org/10.3346/jkms.2016.31.S2.S178,PMC5081299,27775255,CC BY-NC,"Globally, the incidence of communicable diseases has decreased compared to non-communicable diseases. However, chronic communicable diseases such as HIV/AIDS and tuberculosis persist worldwide. Furthermore, emerging new infections such as H1N1 influenza pose a new threat to public health. However, most studies have focused on non-communicable diseases because of their increasing incidence, with fewer studies investigating communicable diseases. Therefore, we estimated the burden of communicable diseases in Korea using national representative 2012 data. To estimate the disability-adjusted life years (DALY), we used cause of death data from the Statistics Korea to estimate the years of life lost (YLL), applied the Korean garbage code algorithm, and used national claims data from the National Health Insurance Service (NHIS) to estimate years lived with disability (YLD). In 2012, the total DALYs of communicable disease were 445 per 100,000, with 129 YLLs per 100,000 and 316 YLDs per 100,000. The total DALYs in men were 468 per 100,000, greater than the 422 per 100,000 DALYs seen in women. The DALYs of lower respiratory infections were the highest value among communicable diseases at 143/100,000 DALYs followed by tuberculosis and upper respiratory infections. The 40-49 years old age group had the largest number of total DALYs. In contrast, the over 80 years old age group had the largest number of total DALYs per 100,000 followed by the 70-79 and 0-9 years old age groups. These results enable the prioritization of interventions related to communicable diseases and can be used for evidence-based public health policies.",2016 Nov 18,"['Lee, Ye-Rin', 'Moon, Kanghee', 'Kim, Young Ae', 'Park, So-Youn', 'Oh, Chang-Mo', 'Lee, Kyung-Suk', 'Oh, In-Hwan']",J Korean Med Sci,,,True
50005544cba05adf4b743e0ec11f39bd8d903cbd,PMC,"Alternative autophagy, brefeldin A and viral trafficking pathways",http://dx.doi.org/10.1080/15548627.2016.1203489,PMC5082769,27439673,CC BY-NC,"Two topics that have attracted recent attention in the field of autophagy concern the source of the membrane that is used to form the autophagosome during macroautophagy and the role of noncanonical autophagic pathways. The 2 topics may converge when considering the intersection of autophagy with viral infection. We suggest that noncanonical autophagy, which is sensitive to treatment with brefeldin A, may converge with the infectious cycles of certain DNA and RNA viruses that utilize membrane from the ER and cis-Golgi.",2016 Jul 20,"['Grose, Charles', 'Klionsky, Daniel J.']",Autophagy,,,True
bb65c5259727bce9f1623452a0af39aa57f9b1bc,PMC,C-reactive protein in outpatients with acute exacerbation of COPD: its relationship with microbial etiology and severity,http://dx.doi.org/10.2147/COPD.S117129,PMC5085274,27799762,CC BY-NC,"BACKGROUND: C-reactive protein (CRP) measurement has proven valuable for detecting exacerbations, but its usefulness in predicting etiology remains controversial. Likewise, its potential value as a marker of severity, which is well established in patients with pneumonia, remains unproven in chronic obstructive pulmonary disease (COPD) exacerbations. METHODS: A cohort study of 118 patients with severe COPD and acute infectious exacerbations were included and followed up over 1 year. Episodes of exacerbations meeting Anthonisen’s criteria type I–II were evaluated, analyzing the etiology and inflammatory response as measured by CRP in blood. RESULTS: A total of 380 episodes were recorded. Full microbiological analysis was available in 265 samples. Haemophilus influenzae was the most commonly isolated bacteria and rhinovirus the most common virus. Median CRP levels from the 265 episodes were higher in the cases with positive cultures for bacteria (58.30 mg/L, interquartile range [IQR] 21.0–28.2) than in episodes only positive for viruses (37.3 mg/L, IQR 18.6–79.1) and cases negative for any microorganism (36.4 mg/L, IQR 10.8–93.7) (P<0.014). H. influenzae and Streptococcus pneumoniae reached the highest CRP levels of 74.5 mg/L (IQR 23.9–167.9) and 74.1 mg/L (IQR 42.0–220.7), respectively. In the 380 exacerbations studied, 227 (~60%) were community-managed, while 153 (~40%) required hospital admission. In the multivariate analysis to assess the influence of inflammatory response on exacerbation severity, baseline hypercapnia (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.46–4.9) and CRP levels >100 mg/L (OR: 4.23, 95% CI: 2.12–8.44) were independent predictors after adjustment for baseline characteristics. CONCLUSION: CRP level was higher in bacterial infections, especially when H. influenzae and S. pneumoniae were isolated. CRP values >100 mg/L were associated with a fourfold increased risk of hospital admission. Therefore, CRP blood levels may be a useful biomarker in the management of exacerbations appearing in patients with severe disease.",2016 Oct 21,"['Gallego, Miguel', 'Pomares, Xavier', 'Capilla, Silvia', 'Marcos, Maria Angeles', 'Suárez, David', 'Monsó, Eduard', 'Montón, Concepción']",Int J Chron Obstruct Pulmon Dis,,,True
d4510e8bc12acbeaa9fc8dd88429b14c02ed6ab1,PMC,Prevalence and Seasonal Distribution of Respiratory Viruses During the 2014 - 2015 Season in Istanbul,http://dx.doi.org/10.5812/jjm.39132,PMC5086027,27800148,CC BY-NC,"BACKGROUND: Acute respiratory tract infection (ARTI) is one of the most common infections worldwide, causing significant morbidity and mortality. OBJECTIVES: This study was conducted to determine the prevalence and seasonal distribution of respiratory viruses in our region, in children and adults with a pre-diagnosis of ARTI. METHODS: A total of 845 nasopharyngeal swab specimens were analyzed with the RespiFinder Smart 22 kit (PathoFinder BV, Netherlands) and the Rotor-Gene 6000 real-time PCR system. RESULTS: At least one pathogen was detected in 612 (72.4%) of the specimens. Overall, 902 pathogens were detected; 821 (91%) were viruses and 81 (9%) were bacteria. The most commonly detected pathogens were influenza A virus (IFV-A) (n = 219), influenza B virus (IFV-B) (n=157), rhinovirus/enterovirus (n = 107), human bocavirus (HBoV) (n = 91), respiratory syncytial virus (RSV) A/B (n = 64), adenovirus (n = 56), human coronaviruses (n = 51), Mycoplasma pneumoniae (n = 49), parainfluenza viruses (n = 40), human metapneumovirus (n = 36), Bordetella pertussis (n = 15), Legionella pneumophila (n = 11), and Chlamydophila pneumoniae (n = 6), respectively. Among the 215 (25.4%) co-infected cases, IFV-A/HBoV and IFV-A/IFV-B were the most common co-infections. IFV-A was the most prevalent agent in all age groups except for children under 5 years of age, in whom RSV A/B was the most common pathogen. Approximately two thirds of the respiratory viruses were detected in early spring and winter, with peaks in January, March, and April. CONCLUSIONS: With regard to the prevalence and seasonal distribution of respiratory viruses, our epidemiological data for the 2014 - 2015 season in Istanbul showed a predominance of IFV-A infections with a peak activity in early spring. Enhanced surveillance and early detection of respiratory viral pathogens can be useful in the diagnosis, treatment, and prevention of ARTIs, and for guiding the development of appropriate public health strategies.",2016 Aug 22,"['Goktas, Safak', 'Sirin, Mumtaz Cem']",Jundishapur J Microbiol,,,True
148a0ab3b9bb851a56bbe926abed11c0d71fc61c,PMC,"Influence of Breed Size, Age, Fecal Quality, and Enteropathogen Shedding on Fecal Calprotectin and Immunoglobulin A Concentrations in Puppies During the Weaning Period",http://dx.doi.org/10.1111/jvim.14255,PMC5089601,27279352,CC BY-NC,"BACKGROUND: Fecal calprotectin and immunoglobulin A (IgA) are markers of intestinal inflammation and immunity in adult dogs. HYPOTHESIS: Fecal calprotectin and IgA concentrations in puppies are not influenced by fecal moisture in puppies but by enteropathogen shedding. ANIMALS: Three hundred and twenty‐four puppies. METHODS: Fecal consistency was assessed by gross examination. Fecal moisture was evaluated before and after lyophilization. Canine parvovirus and coronavirus were detected in feces by qPCR and qRT‐PCR respectively. Giardia intestinalis antigen was quantified by ELISA. The standard McMaster flotation technique was used to detect eggs and oocysts in feces. Fecal calprotectin and IgA concentrations were quantified by in‐house radioimmunoassays. RESULTS: For each marker (IgA and calprotectin), a strong positive correlation was observed between concentration in fresh feces and concentration in fecal dry matter. 75.6% of the puppies were found to be infected by at ≥1 of the enteropathogens evaluated. Fecal calprotectin concentration was significantly influenced by age (P = .001), with higher concentrations in younger puppies, but not by viral (P = .863) or parasitic infection (P = .791). Fecal IgA concentration was significantly influenced by enteropathogen shedding (P = .01), with a lower fecal IgA concentration in puppies shedding at ≥1 enteropathogen compared to puppies without any enteropathogen shedding, but not by age. CONCLUSIONS: Fecal calprotectin and IgA are of no diagnostic value to detect presence of enteropathogens in clinically healthy puppies or puppies with abnormal feces, but could help to better understand the maturation of digestive tract.",2016 Jun 8 Jul-Aug,"['Grellet, A.', 'Heilmann, R.M.', 'Polack, B.', 'Feugier, A.', 'Boucraut‐Baralon, C.', 'Grandjean, D.', 'Grützner, N.', 'Suchodolski, J. S.', 'Steiner, J.M.', 'Chastant‐Maillard, S.']",J Vet Intern Med,,,True
025ed2caa0ae1ab7f04d3479116e6ed2a334938d,PMC,Clinicopathological Phenotype of Autosomal Recessive Cholesterol Deficiency in Holstein Cattle,http://dx.doi.org/10.1111/jvim.13976,PMC5089636,27279263,CC BY-NC,"BACKGROUND: Cholesterol deficiency (CD), a newly identified autosomal recessive genetic defect in Holstein cattle, is associated with clinical signs of diarrhea, failure to thrive, and hypocholesterolemia. HYPOTHESIS/OBJECTIVES: The objective is to describe the clinicopathological phenotype of affected Holstein cattle homozygous for the causative apolipoprotein B gene (APOB) mutation. ANIMALS: Six Holstein cattle, 5 calves with a clinical history of chronic diarrhea, and 1 heifer with erosions in the buccal cavity and neurologic symptoms were admitted to the Clinic for Ruminants. METHODS: This case review included a full clinical examination, a complete blood count, blood chemistry, and measurements of cholesterol and triglycerides. The animals were euthanized and necropsied. A PCR‐based direct gene test was applied to determine the APOB genotype. RESULTS: All 6 animals were inbred, could be traced back to the sire Maughlin Storm, and were confirmed homozygous for the APOB mutation. The clinical phenotype included poor development, underweight, and intermittent diarrhea in the calves, and neurologic signs in the heifer included hypermetria and pacing. Hypocholesterolemia and low triglycerides concentrations were present in all animals. The pathological phenotype of all animals was steatorrhea with enterocytes of the small intestine containing intracytoplasmic lipid vacuoles. The peripheral nervous system of the heifer displayed degenerative changes. CONCLUSIONS AND CLINICAL IMPORTANCE: Suspicion of CD in Holstein cattle is based on the presence of chronic diarrhea with no evidence of primary infections. Confirmation of the associated APOB gene mutation is needed. Additionally, the heifer demonstrated primarily signs of neurologic disease providing an unexpected phenotype of CD.",2016 Jun 8 Jul-Aug,"['Mock, T.', 'Mehinagic, K.', 'Menzi, F.', 'Studer, E.', 'Oevermann, A.', 'Stoffel, M.H.', 'Drögemüller, C.', 'Meylan, M.', 'Regenscheit, N.']",J Vet Intern Med,,,True
5036d9acb850bbb3705be78b3ab64dec35d68b27,PMC,Prevalence and Clinicopathological Features of Triaditis in a Prospective Case Series of Symptomatic and Asymptomatic Cats,http://dx.doi.org/10.1111/jvim.14356,PMC5089651,27296565,CC BY-NC,"BACKGROUND: The term triaditis designates the concurrent presence of idiopathic inflammatory bowel disease (IBD), cholangitis, and pancreatitis in cats. HYPOTHESIS/OBJECTIVES: The histopathology of concurrent, but often subclinical, inflammatory processes in the small intestine, liver, and pancreas of cats is poorly described. We aimed to investigate the frequency of enteritis, cholangitis, pancreatitis, or some combination of these in symptomatic and asymptomatic cats, compare clinicopathological features, and correlate histopathological with laboratory findings. ANIMALS: Domestic cats (27 symptomatic, 20 asymptomatic, and 8 normal). METHODS: Prospective study. Physical examination, laboratory variables (CBC, serum biochemistry profile, serum thyroxine concentration, serum feline trypsin‐like immunoreactivity [fTLI], feline lipase immunoreactivity [fPLI, as measured by Spec fPL (®)], urinalysis, and fecal analysis), imaging, and histopathological examinations were conducted. Feline liver, pancreas, and small intestine were biopsied during laparotomy. RESULTS: Inflammatory lesions were detected in 47 cats (27 symptomatic, 20 asymptomatic). In total, 20 cats had histopathologic lesions of IBD (13/47, 27.7%), cholangitis (6/47, 12.8%), or pancreatitis (1/47, 2.1%) alone, or inflammation involving >1 organ (27/47, 57.4%). More specifically, 16/47 cats (34.0%) had concurrent lesions of IBD and cholangitis, 3/47 (6.4%) of IBD and pancreatitis, and 8/47 cats (17%) of triaditis. Triaditis was identified only in symptomatic cats (8/27, 29.6%). A mild, positive correlation was detected between the severity (score) of IBD lesions and the number of comorbidities (rho = +0.367, P = .022). CONCLUSIONS AND CLINICAL IMPORTANCE: Histopathological evidence of IBD or IBD with comorbidities was detected in both symptomatic and asymptomatic cats. The possibility of triaditis should be considered in symptomatic cats with severe IBD.",2016 Jun 14 Jul-Aug,"['Fragkou, F.C.', 'Adamama‐Moraitou, K.K.', 'Poutahidis, T.', 'Prassinos, N.N.', 'Kritsepi‐Konstantinou, M.', 'Xenoulis, P.G.', 'Steiner, J.M.', 'Lidbury, J.A.', 'Suchodolski, J.S.', 'Rallis, T.S.']",J Vet Intern Med,,,True
5c66cc1354cf791eb0cd326ff6314b980f3e3e5c,PMC,Prevalence and Clinicopathological Features of Triaditis in a Prospective Case Series of Symptomatic and Asymptomatic Cats,http://dx.doi.org/10.1111/jvim.14356,PMC5089651,27296565,CC BY-NC,"BACKGROUND: The term triaditis designates the concurrent presence of idiopathic inflammatory bowel disease (IBD), cholangitis, and pancreatitis in cats. HYPOTHESIS/OBJECTIVES: The histopathology of concurrent, but often subclinical, inflammatory processes in the small intestine, liver, and pancreas of cats is poorly described. We aimed to investigate the frequency of enteritis, cholangitis, pancreatitis, or some combination of these in symptomatic and asymptomatic cats, compare clinicopathological features, and correlate histopathological with laboratory findings. ANIMALS: Domestic cats (27 symptomatic, 20 asymptomatic, and 8 normal). METHODS: Prospective study. Physical examination, laboratory variables (CBC, serum biochemistry profile, serum thyroxine concentration, serum feline trypsin‐like immunoreactivity [fTLI], feline lipase immunoreactivity [fPLI, as measured by Spec fPL (®)], urinalysis, and fecal analysis), imaging, and histopathological examinations were conducted. Feline liver, pancreas, and small intestine were biopsied during laparotomy. RESULTS: Inflammatory lesions were detected in 47 cats (27 symptomatic, 20 asymptomatic). In total, 20 cats had histopathologic lesions of IBD (13/47, 27.7%), cholangitis (6/47, 12.8%), or pancreatitis (1/47, 2.1%) alone, or inflammation involving >1 organ (27/47, 57.4%). More specifically, 16/47 cats (34.0%) had concurrent lesions of IBD and cholangitis, 3/47 (6.4%) of IBD and pancreatitis, and 8/47 cats (17%) of triaditis. Triaditis was identified only in symptomatic cats (8/27, 29.6%). A mild, positive correlation was detected between the severity (score) of IBD lesions and the number of comorbidities (rho = +0.367, P = .022). CONCLUSIONS AND CLINICAL IMPORTANCE: Histopathological evidence of IBD or IBD with comorbidities was detected in both symptomatic and asymptomatic cats. The possibility of triaditis should be considered in symptomatic cats with severe IBD.",2016 Jun 14 Jul-Aug,"['Fragkou, F.C.', 'Adamama‐Moraitou, K.K.', 'Poutahidis, T.', 'Prassinos, N.N.', 'Kritsepi‐Konstantinou, M.', 'Xenoulis, P.G.', 'Steiner, J.M.', 'Lidbury, J.A.', 'Suchodolski, J.S.', 'Rallis, T.S.']",J Vet Intern Med,,,False
2a1c5b2541cb958a6280094aa3c1cd2e414fb468,PMC,Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination,http://dx.doi.org/10.3791/54348,PMC5092010,27685467,CC BY-NC-ND,"A major hallmark of the autoimmune demyelinating disease multiple sclerosis (MS) is immune cell infiltration into the brain and spinal cord resulting in myelin destruction, which not only slows conduction of nerve impulses, but causes axonal injury resulting in motor and cognitive decline. Current treatments for MS focus on attenuating immune cell infiltration into the central nervous system (CNS). These treatments decrease the number of relapses, improving quality of life, but do not completely eliminate relapses so long-term disability is not improved. Therefore, therapeutic agents that protect the CNS are warranted. In both animal models as well as human patients with MS, T cell entry into the CNS is generally considered the initiating inflammatory event. In order to assess if a drug protects the CNS, any potential effects on immune cell infiltration or proliferation in the periphery must be ruled out. This protocol describes how to determine whether CNS protection observed after drug intervention is a consequence of attenuating CNS-infiltrating immune cells or blocking death of CNS cells during inflammatory insults. The ability to examine MS treatments that are protective to the CNS during inflammatory insults is highly critical for the advancement of therapeutic strategies since current treatments reduce, but do not completely eliminate, relapses (i.e., immune cell infiltration), leaving the CNS vulnerable to degeneration.",2016 Sep 12,"['Evonuk, Kirsten S.', 'Moseley, Carson E.', 'Doyle, Ryan E.', 'Weaver, Casey T.', 'DeSilva, Tara M.']",J Vis Exp,,,True
7048d2fc8e7a1daab3747ea6d2257a874a9723b0,PMC,Serological survey of Encephalitozoon cuniculi infection in cats in Japan,http://dx.doi.org/10.1292/jvms.15-0545,PMC5095633,27320966,CC BY-NC-ND,"Antibodies to Encephalitozoon cuniculi (E. cuniculi) were examined by enzyme-linked immunosorbent assay using E. cuniculi PTP2 recombinant protein from serum samples that had been collected from a total of 295 cats in Japan. Of these samples, 6.1% (18/295) had antibodies against E. cuniculi, which included 6.3% (6/96) of the male cats and 6.0% (12/199) of the female cats. The incidence was slightly higher in feral cats (8.3%, 11/132) compared to domesticated cats (4.3%, 7/163). This suggests the possibility that the cats of our country have become a reservoir of E. cuniculi. This study is the first to demonstrate the prevalence of E. cuniculi infection in cats in Japan.",2016 Oct 20,"['TSUKADA, Ryusuke', 'OSAKA, Yuki', 'TAKANO, Tomomi', 'SASAKI, Mizuki', 'INOSE, Mitsuhiro', 'IKADAI, Hiromi']",J Vet Med Sci,,,True
041adbe00a7ca71fcbc38ff4406297ce86e93a6a,PMC,"A DESCRIPTIVE STUDY OF PANDEMIC INFLUENZA A(H1N1)PDM09 IN BRAZIL, 2009 - 2010",http://dx.doi.org/10.1590/S1678-9946201658078,PMC5096632,27828619,CC BY-NC,"Influenza A viruses undergo frequent antigenic mutations and may thus cause seasonal epidemics and pandemics. The aim of this study was to recover the epidemiological history of the pandemic influenza A(H1N1)pdm09 in Brazil. A descriptive study was conducted in 2009-2010. The Brazilian Information System for reportable diseases (SINAN) was the data source. A total of 105,054 suspected cases of influenza A(H1N1)pdm09 were reported to SINAN. Of these, 53,797 (51.2%) were classified as the new influenza virus subtype. Among the confirmed cases, 56.7% were female, the mean age was 26.31 (SD ± 18.1) years. Fever was the most common sign among the confirmed cases (99.7%) and the presence of comorbidities was reported in 32.5% of cases. In 2009 there were confirmed cases in all 26 Brazilian States and the Federal District. The incidence (per 100,000 inhabitants) of severe influenza in the population was 28.0 in 2009 and 0.5 in 2010. The states of Paraná (301.3), Santa Catarina (36.0) and Rio Grande do Sul (27.4) presented the highest incidence; 46.4% of the confirmed cases were hospitalized and 47,643 were cured (93.8%). The case-fatality rate was 3.9% in 2009. The pandemic virus A(H1N1)pdm09 hit Brazil between April/2009 and December/2010 with an important difference in the geographic pattern distribution of the cases from the northeast to the south of the country. Children and young adults were the most affected. The limitations of the study were data quality and inconsistencies in the final classification of cases in SINAN. This study highlights the urgent need for improvements in the surveillance of emerging diseases in Brazil.",2016 Nov 3,"['ROSSETTO, Erika Valeska', 'LUNA, Expedito José de Albuquerque']",Rev Inst Med Trop Sao Paulo,,,True
d58b1736b91a0fd016aa5a22ca12da23235d637a,PMC,"Antibody Engineering & Therapeutics 2016: The Antibody Society's annual meeting, December 11–15, 2016, San Diego, CA",http://dx.doi.org/10.1080/19420862.2016.1227665,PMC5098447,27557809,CC BY-NC,"Antibody Engineering & Therapeutics, the largest meeting devoted to antibody science and technology and the annual meeting of The Antibody Society, will be held in San Diego, CA on December 11-15, 2016. Each of 14 sessions will include six presentations by leading industry and academic experts. In this meeting preview, the session chairs discuss the relevance of their topics to current and future antibody therapeutics development. Session topics include bispecifics and designer polyclonal antibodies; antibodies for neurodegenerative diseases; the interface between passive and active immunotherapy; antibodies for non-cancer indications; novel antibody display, selection and screening technologies; novel checkpoint modulators / immuno-oncology; engineering antibodies for T-cell therapy; novel engineering strategies to enhance antibody functions; and the biological Impact of Fc receptor engagement. The meeting will open with keynote speakers Dennis R. Burton (The Scripps Research Institute), who will review progress toward a neutralizing antibody-based HIV vaccine; Olivera J. Finn, (University of Pittsburgh School of Medicine), who will discuss prophylactic cancer vaccines as a source of therapeutic antibodies; and Paul Richardson (Dana-Farber Cancer Institute), who will provide a clinical update on daratumumab for multiple myeloma. In a featured presentation, a representative of the World Health Organization's INN expert group will provide a perspective on antibody naming. “Antibodies to watch in 2017” and progress on The Antibody Society's 2016 initiatives will be presented during the Society's special session. In addition, two pre-conference workshops covering ways to accelerate antibody drugs to the clinic and the applications of next-generation sequencing in antibody discovery and engineering will be held on Sunday December 11, 2016.",2016 Aug 24,"['Larrick, James W.', 'Alfenito, Mark R.', 'Scott, Jamie K.', 'Parren, Paul W. H. I.', 'Burton, Dennis R.', 'Bradbury, Andrew R. M.', 'Lemere, Cynthia A.', 'Messer, Anne', 'Huston, James S.', 'Carter, Paul J.', 'Veldman, Trudi', 'Chester, Kerry A.', 'Schuurman, Janine', 'Adams, Gregory P.', 'Reichert, Janice M.']",MAbs,,,True
39708f10658e8e33983d0b2ebb570bdd00c5df46,PMC,Techno-economic analysis of a transient plant-based platform for monoclonal antibody production,http://dx.doi.org/10.1080/19420862.2016.1227901,PMC5098453,27559626,CC BY-NC,"Plant-based biomanufacturing of therapeutic proteins is a relatively new platform with a small number of commercial-scale facilities, but offers advantages of linear scalability, reduced upstream complexity, reduced time to market, and potentially lower capital and operating costs. In this study we present a detailed process simulation model for a large-scale new “greenfield” biomanufacturing facility that uses transient agroinfiltration of Nicotiana benthamiana plants grown hydroponically indoors under light-emitting diode lighting for the production of a monoclonal antibody. The model was used to evaluate the total capital investment, annual operating cost, and cost of goods sold as a function of mAb expression level in the plant (g mAb/kg fresh weight of the plant) and production capacity (kg mAb/year). For the Base Case design scenario (300 kg mAb/year, 1 g mAb/kg fresh weight, and 65% recovery in downstream processing), the model predicts a total capital investment of $122 million dollars and cost of goods sold of $121/g including depreciation. Compared with traditional biomanufacturing platforms that use mammalian cells grown in bioreactors, the model predicts significant reductions in capital investment and >50% reduction in cost of goods compared with published values at similar production scales. The simulation model can be modified or adapted by others to assess the profitability of alternative designs, implement different process assumptions, and help guide process development and optimization.",2016 Aug 25,"['Nandi, Somen', 'Kwong, Aaron T.', 'Holtz, Barry R.', 'Erwin, Robert L.', 'Marcel, Sylvain', 'McDonald, Karen A.']",MAbs,,,True
8bc2d0429d1c8168ddb3869ad0a81cebfe5fd8ac,PMC,Middle East respiratory syndrome coronavirus disease is rare in children: An update from Saudi Arabia,http://dx.doi.org/10.5409/wjcp.v5.i4.391,PMC5099592,27872828,CC BY-NC,"AIM: To summarize the reported Middle East respiratory syndrome-coronavirus (MERS-CoV) cases, the associated clinical presentations and the outcomes. METHODS: We searched the Saudi Ministry of Health website, the World Health Organization website, and the Flutracker website. We also searched MEDLINE and PubMed for the keywords: Middle East respiratory syndrome-coronavirus, MERS-CoV in combination with pediatric, children, childhood, infancy and pregnancy from the initial discovery of the virus in 2012 to 2016. The retrieved articles were also read to further find other articles. Relevant data were placed into an excel sheet and analyzed accordingly. Descriptive analytic statistics were used in the final analysis as deemed necessary. RESULTS: From June 2012 to April 19, 2016, there were a total of 31 pediatric MERS-CoV cases. Of these cases 13 (42%) were asymptomatic and the male to female ratio was 1.7:1. The mean age of patients was 9.8 ± 5.4 years. Twenty-five (80.6%) of the cases were reported from the Kingdom of Saudi Arabia. The most common source of infection was household contact (10 of 15 with reported source) and 5 patients acquired infection within a health care facility. Using real time reverse transcriptase polymerase chain reaction of pediatric patients revealed that 9 out of 552 (1.6%) was positive in the Kingdom of Saudi Arabia. CONCLUSION: Utilizing serology for MERS-CoV infection in Jordan and Saudi Arabia did not reveal any positive patients. Thus, the number of the pediatric MERS-CoV is low; the exact reason for the low prevalence of the disease in children is not known.",2016 Nov 8,"['Al-Tawfiq, Jaffar A', 'Kattan, Rana F', 'Memish, Ziad A']",World J Clin Pediatr,,,True
49d10e98d15b16cd6d0b522b21714401d767dcc2,PMC,Clinical Features and Radiological Findings of Adenovirus Pneumonia Associated with Progression to Acute Respiratory Distress Syndrome: A Single Center Study in 19 Adult Patients,http://dx.doi.org/10.3348/kjr.2016.17.6.940,PMC5102922,27833410,CC BY-NC,"OBJECTIVE: To describe radiologic findings of adenovirus pneumonia and to understand clinico-radiological features associated with progression to acute respiratory distress syndrome (ARDS) in patients with adenovirus pneumonia. MATERIALS AND METHODS: This study included 19 patients diagnosed with adenovirus pneumonia at a tertiary referral center, in the period between March 2003 and April 2015. Clinical findings were reviewed, and two radiologists assessed imaging findings by consensus. Chi-square, Fisher's exact, and Student's t tests were used for comparing patients with and without subsequent development of ARDS. RESULTS: Of 19 patients, nine were immunocompromised, and 10 were immunocompetent. Twelve patients (63%) progressed to ARDS, six of whom (32%) eventually died from the disease. The average time for progression to ARDS from symptom onset was 9.6 days. Initial chest radiographic findings were normal (n = 2), focal opacity (n = 9), or multifocal or diffuse opacity (n = 8). Computed tomography (CT) findings included bilateral (n = 17) or unilateral (n = 2) ground-glass opacity with consolidation (n = 14) or pleural effusion (n = 11). Patients having subsequent ARDS had a higher probability of pleural effusion and a higher total CT extent compared with the non-ARDS group (p = 0.010 and 0.007, respectively). However, there were no significant differences in clinical variables such as patient age and premorbid condition. CONCLUSION: Adenovirus pneumonia demonstrates high rates of ARDS and mortality, regardless of patient age and premorbid conditions, in the tertiary care setting. Large disease extent and presence of pleural effusion on CT are factors suggestive of progression to ARDS.",2016 Oct 31 Nov-Dec,"['Cha, Min Jae', 'Chung, Myung Jin', 'Lee, Kyung Soo', 'Kim, Tae Jung', 'Kim, Tae Sung', 'Chong, Semin', 'Han, Jungho']",Korean J Radiol,,,True
284541395ddc07d44ccd2d3da2ba060505a01407,PMC,Ehrlichia secretes Etf-1 to induce autophagy and capture nutrients for its growth through RAB5 and class III phosphatidylinositol 3-kinase,http://dx.doi.org/10.1080/15548627.2016.1217369,PMC5103349,27541856,CC BY-NC,"Ehrlichia chaffeensis is an obligatory intracellular bacterium that causes a potentially fatal emerging zoonosis, human monocytic ehrlichiosis. E. chaffeensis has a limited capacity for biosynthesis and metabolism and thus depends mostly on host-synthesized nutrients for growth. Although the host cell cytoplasm is rich with these nutrients, as E. chaffeensis is confined within the early endosome-like membrane-bound compartment, only host nutrients that enter the compartment can be used by this bacterium. How this occurs is unknown. We found that ehrlichial replication depended on autophagy induction involving class III phosphatidylinositol 3-kinase (PtdIns3K) activity, BECN1 (Beclin 1), and ATG5 (autophagy-related 5). Ehrlichia acquired host cell preincorporated amino acids in a class III PtdIns3K-dependent manner and ehrlichial growth was enhanced by treatment with rapamycin, an autophagy inducer. Moreover, ATG5 and RAB5A/B/C were routed to ehrlichial inclusions. RAB5A/B/C siRNA knockdown, or overexpression of a RAB5-specific GTPase-activating protein or dominant-negative RAB5A inhibited ehrlichial infection, indicating the critical role of GTP-bound RAB5 during infection. Both native and ectopically expressed ehrlichial type IV secretion effector protein, Etf-1, bound RAB5 and the autophagy-initiating class III PtdIns3K complex, PIK3C3/VPS34, and BECN1, and homed to ehrlichial inclusions. Ectopically expressed Etf-1 activated class III PtdIns3K as in E. chaffeensis infection and induced autophagosome formation, cleared an aggregation-prone mutant huntingtin protein in a class III PtdIns3K-dependent manner, and enhanced ehrlichial proliferation. These data support the notion that E. chaffeensis secretes Etf-1 to induce autophagy to repurpose the host cytoplasm and capture nutrients for its growth through RAB5 and class III PtdIns3K, while avoiding autolysosomal killing.",2016 Aug 19,"['Lin, Mingqun', 'Liu, Hongyan', 'Xiong, Qingming', 'Niu, Hua', 'Cheng, Zhihui', 'Yamamoto, Akitsugu', 'Rikihisa, Yasuko']",Autophagy,,,True
cd92f91038067e7a10aa27d676ce696e1e4d67ce,PMC,Dimethyloxaloylglycine increases bone repair capacity of adipose-derived stem cells in the treatment of osteonecrosis of the femoral head,http://dx.doi.org/10.3892/etm.2016.3698,PMC5103711,27882083,CC BY-NC-ND,"Mesenchymal stem cells have been widely studied to promote local bone regeneration of osteonecrosis of the femoral head (ONFH). Previous studies observed that dimethyloxaloylglycine (DMOG) enhanced the angiogenic and osteogenic activity of mesenchymal stem cells by activating the expression of hypoxia inducible factor-1α (HIF-1α), thereby improving the bone repair capacity of mesenchymal stem cells. In the present study, it was investigated whether DMOG could increase the bone repair capacity of adipose-derived stem cells (ASCs) in the treatment of ONFH. Western blot analysis was performed to detect HIF-1α protein expression in ASCs treated with different concentrations of DMOG. The results showed DMOG enhanced HIF-1α expression in ASCs in a dose-dependent manner at least for 7 days. Furthermore, DMOG-treated ASCs were transplanted into the necrotic area of a rabbit model of ONFH to treat the disease. Four weeks later, micro-computed tomography (CT) quantitative analysis showed that 58.8±7.4% of the necrotic area was regenerated in the DMOG-treated ASCs transplantation group, 45.5±3.4% in normal ASCs transplantation group, 25.2±2.8% in only core decompression group and 10.6±2.6% in the untreated group. Histological analysis showed that transplantation of DMOG-treated ASCs clearly improved the bone regeneration of the necrotic area compared with the other three groups. Micro-CT and immunohistochemical analysis demonstrated the revasculation of the necrotic area were also increased significantly in the DMOG-treated ASC group compared with the control groups. Thus, it is hypothesized that DMOG could increase the bone repair capacity of ASCs through enhancing HIF-1α expression in the treatment of ONFH.",2016 Nov 13,"['Zhu, Zhen-Hong', 'Song, Wen-Qi', 'Zhang, Chang-Qing', 'Yin, Ji-Min']",Exp Ther Med,,,True
f0c369c6a223586d56037b92314080d4654c7d94,PMC,Importance of Specimen Type and Quality in Diagnosing Middle East Respiratory Syndrome,http://dx.doi.org/10.3343/alm.2017.37.1.81,PMC5107625,27834073,CC BY-NC,,2017 Jan 1,"['Huh, Hee Jae', 'Ko, Jae-Hoon', 'Kim, Young-Eun', 'Park, Chang-Hun', 'Hong, Geehay', 'Choi, Rihwa', 'Yu, Shinae', 'Cho, Sun Young', 'Kang, Ji-Man', 'Lee, Myoung-Keun', 'Ki, Chang-Seok', 'Kang, Eun-Suk', 'Lee, Nam Yong', 'Kim, Jong-Won', 'Kim, Yae-Jean', 'Ha, Young Eun', 'Kang, Cheol-In', 'Chung, Doo Ryeon', 'Peck, Kyong Ran', 'Song, Jae-Hoon']",Ann Lab Med,,,True
ecd341e70316d124587fb8370d949fbf5524bd2f,PMC,Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection,http://dx.doi.org/10.1016/j.antiviral.2016.06.003,PMC5109928,27312105,CC BY-NC-ND,"Middle East respiratory syndrome coronavirus (MERS-CoV) is continuously spreading and causing severe and fatal acute respiratory disease in humans. Prophylactic and therapeutic strategies are therefore urgently needed to control MERS-CoV infection. Here, we generated a humanized monoclonal antibody (mAb), designated hMS-1, which targeted the MERS-CoV receptor-binding domain (RBD) with high affinity. hMS-1 significantly blocked MERS-CoV RBD binding to its viral receptor, human dipeptidyl peptidase 4 (hDPP4), potently neutralized infection by a prototype MERS-CoV, and effectively cross-neutralized evolved MERS-CoV isolates through recognizing highly conserved RBD epitopes. Notably, single-dose treatment with hMS-1 completely protected hDPP4 transgenic (hDPP4-Tg) mice from lethal infection with MERS-CoV. Taken together, our data suggest that hMS-1 might be developed as an effective immunotherapeutic agent to treat patients infected with MERS-CoV, particularly in emergent cases.",2016 Aug 14,"['Qiu, Hongjie', 'Sun, Shihui', 'Xiao, He', 'Feng, Jiannan', 'Guo, Yan', 'Tai, Wanbo', 'Wang, Yufei', 'Du, Lanying', 'Zhao, Guangyu', 'Zhou, Yusen']",Antiviral Res,,,True
c10a8172b1572b5f5d94ff56417549b51db7405c,PMC,Interferon lambda 4 expression is suppressed by the host during viral infection,http://dx.doi.org/10.1084/jem.20160437,PMC5110018,27799623,CC BY-NC-SA,"Interferon (IFN) lambdas are critical antiviral effectors in hepatic and mucosal infections. Although IFNλ1, IFNλ2, and IFNλ3 act antiviral, genetic association studies have shown that expression of the recently discovered IFNL4 is detrimental to hepatitis C virus (HCV) infection through a yet unknown mechanism. Intriguingly, human IFNL4 harbors a genetic variant that introduces a premature stop codon. We performed a molecular and biochemical characterization of IFNλ4 to determine its role and regulation of expression. We found that IFNλ4 exhibits similar antiviral activity to IFNλ3 without negatively affecting antiviral IFN activity or cell survival. We show that humans deploy several mechanisms to limit expression of functional IFNλ4 through noncoding splice variants and nonfunctional protein isoforms. Furthermore, protein-coding IFNL4 mRNA are not loaded onto polyribosomes and lack a strong polyadenylation signal, resulting in poor translation efficiency. This study provides mechanistic evidence that humans suppress IFNλ4 expression, suggesting that immune function is dependent on other IFNL family members.",2016 Nov 14,"['Hong, MeeAe', 'Schwerk, Johannes', 'Lim, Chrissie', 'Kell, Alison', 'Jarret, Abigail', 'Pangallo, Joseph', 'Loo, Yueh-Ming', 'Liu, Shuanghu', 'Hagedorn, Curt H.', 'Gale, Michael', 'Savan, Ram']",J Exp Med,,,True
82792dd5a551a6cb725c1e41e82408188ae907e0,PMC,Interferon lambda 4 expression is suppressed by the host during viral infection,http://dx.doi.org/10.1084/jem.20160437,PMC5110018,27799623,CC BY-NC-SA,"Interferon (IFN) lambdas are critical antiviral effectors in hepatic and mucosal infections. Although IFNλ1, IFNλ2, and IFNλ3 act antiviral, genetic association studies have shown that expression of the recently discovered IFNL4 is detrimental to hepatitis C virus (HCV) infection through a yet unknown mechanism. Intriguingly, human IFNL4 harbors a genetic variant that introduces a premature stop codon. We performed a molecular and biochemical characterization of IFNλ4 to determine its role and regulation of expression. We found that IFNλ4 exhibits similar antiviral activity to IFNλ3 without negatively affecting antiviral IFN activity or cell survival. We show that humans deploy several mechanisms to limit expression of functional IFNλ4 through noncoding splice variants and nonfunctional protein isoforms. Furthermore, protein-coding IFNL4 mRNA are not loaded onto polyribosomes and lack a strong polyadenylation signal, resulting in poor translation efficiency. This study provides mechanistic evidence that humans suppress IFNλ4 expression, suggesting that immune function is dependent on other IFNL family members.",2016 Nov 14,"['Hong, MeeAe', 'Schwerk, Johannes', 'Lim, Chrissie', 'Kell, Alison', 'Jarret, Abigail', 'Pangallo, Joseph', 'Loo, Yueh-Ming', 'Liu, Shuanghu', 'Hagedorn, Curt H.', 'Gale, Michael', 'Savan, Ram']",J Exp Med,,,False
c3e25d0cb02656c82dfac2860225f14588489066,PMC,Analysis of intrapatient heterogeneity uncovers the microevolution of Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1101/mcs.a001214,PMC5111008,27900364,CC BY-NC,"Genome sequence analysis of Middle East respiratory syndrome coronavirus (MERS-CoV) variants from patient specimens has revealed the evolutionary dynamics and mechanisms of pathogenesis of the virus. However, most studies have analyzed the consensus sequences of MERS-CoVs, precluding an investigation of intrapatient heterogeneity. Here, we analyzed non–consensus sequences to characterize intrapatient heterogeneity in cases associated with the 2015 outbreak of MERS in South Korea. Deep-sequencing analysis of MERS-CoV genomes performed on specimens from eight patients revealed significant intrapatient variation; therefore, sequence heterogeneity was further analyzed using targeted deep sequencing. A total of 35 specimens from 24 patients (including a super-spreader) were sequenced to detect and analyze variants displaying intrapatient heterogeneity. Based on the analysis of non–consensus sequences, we demonstrated the intrapatient heterogeneity of MERS-CoVs, with the highest level in the super-spreader specimen. The heterogeneity could be transmitted in a close association with variation in the consensus sequences, suggesting the occurrence of multiple MERS-CoV infections. Analysis of intrapatient heterogeneity revealed a relationship between D510G and I529T mutations in the receptor-binding domain (RBD) of the viral spike glycoprotein. These two mutations have been reported to reduce the affinity of the RBD for human CD26. Notably, although the frequency of both D510G and I529T varied greatly among specimens, the combined frequency of the single mutants was consistently high (87.7% ± 1.9% on average). Concurrently, the frequency of occurrence of the wild type at the two positions was only 6.5% ± 1.7% on average, supporting the hypothesis that selection pressure exerted by the host immune response played a critical role in shaping genetic variants and their interaction in human MERS-CoVs during the outbreak.",2016 Nov,"['Park, Donghyun', 'Huh, Hee Jae', 'Kim, Yeon Jeong', 'Son, Dae-Soon', 'Jeon, Hyo-Jeong', 'Im, Eu-Hyun', 'Kim, Jong-Won', 'Lee, Nam Yong', 'Kang, Eun-Suk', 'Kang, Cheol In', 'Chung, Doo Ryeon', 'Ahn, Jin-Hyun', 'Peck, Kyong Ran', 'Choi, Sun Shim', 'Kim, Yae-Jean', 'Ki, Chang-Seok', 'Park, Woong-Yang']",Cold Spring Harb Mol Case Stud,,,True
d6951136eb1f783092f894b3d7c98e896cf3e921,PMC,Prevalence of Enteropathogens in Dogs Attending 3 Regional Dog Parks in Northern California,http://dx.doi.org/10.1111/jvim.14603,PMC5115183,27859745,CC BY-NC,"BACKGROUND: The prevalence and risk factors for infection with enteropathogens in dogs frequenting dog parks have been poorly documented, and infected dogs can pose a potential zoonotic risk for owners. HYPOTHESIS/OBJECTIVES: To determine the prevalence and risk factors of infection with enteropathogens and zoonotic Giardia strains in dogs attending dog parks in Northern California and to compare results of fecal flotation procedures performed at a commercial and university parasitology laboratory. ANIMALS: Three‐hundred dogs attending 3 regional dog parks in Northern California. METHODS: Prospective study. Fresh fecal specimens were collected from all dogs, scored for consistency, and owners completed a questionnaire. Specimens were analyzed by fecal centrifugation flotation, DFA, and PCR for detection of 11 enteropathogens. Giardia genotyping was performed for assemblage determination. RESULTS: Enteropathogens were detected in 114/300 dogs (38%), of which 62 (54%) did not have diarrhea. Frequency of dog park attendance correlated significantly with fecal consistency (P = .0039), but did not correlate with enteropathogen detection. Twenty‐seven dogs (9%) were infected with Giardia, and genotyping revealed nonzoonotic assemblages C and D. The frequency of Giardia detection on fecal flotation was significantly lower at the commercial laboratory versus the university laboratory (P = .013), and PCR for Giardia was negative in 11/27 dogs (41%) that were positive on fecal flotation or DFA. CONCLUSIONS AND CLINICAL IMPORTANCE: Enteropathogens were commonly detected in dogs frequenting dog parks, and infection with Giardia correlated with fecal consistency. PCR detection of Giardia had limited diagnostic utility, and detection of Giardia cysts by microscopic technique can vary among laboratories.",2016 Nov 11 Nov-Dec,"['Hascall, K.L.', 'Kass, P.H.', 'Saksen, J.', 'Ahlmann, A.', 'Scorza, A.V.', 'Lappin, M.R.', 'Marks, S.L.']",J Vet Intern Med,,,True
8b3099d92708e803acc22514d5f65fb497d4c240,PMC,Prevalence of Enteropathogens in Dogs Attending 3 Regional Dog Parks in Northern California,http://dx.doi.org/10.1111/jvim.14603,PMC5115183,27859745,CC BY-NC,"BACKGROUND: The prevalence and risk factors for infection with enteropathogens in dogs frequenting dog parks have been poorly documented, and infected dogs can pose a potential zoonotic risk for owners. HYPOTHESIS/OBJECTIVES: To determine the prevalence and risk factors of infection with enteropathogens and zoonotic Giardia strains in dogs attending dog parks in Northern California and to compare results of fecal flotation procedures performed at a commercial and university parasitology laboratory. ANIMALS: Three‐hundred dogs attending 3 regional dog parks in Northern California. METHODS: Prospective study. Fresh fecal specimens were collected from all dogs, scored for consistency, and owners completed a questionnaire. Specimens were analyzed by fecal centrifugation flotation, DFA, and PCR for detection of 11 enteropathogens. Giardia genotyping was performed for assemblage determination. RESULTS: Enteropathogens were detected in 114/300 dogs (38%), of which 62 (54%) did not have diarrhea. Frequency of dog park attendance correlated significantly with fecal consistency (P = .0039), but did not correlate with enteropathogen detection. Twenty‐seven dogs (9%) were infected with Giardia, and genotyping revealed nonzoonotic assemblages C and D. The frequency of Giardia detection on fecal flotation was significantly lower at the commercial laboratory versus the university laboratory (P = .013), and PCR for Giardia was negative in 11/27 dogs (41%) that were positive on fecal flotation or DFA. CONCLUSIONS AND CLINICAL IMPORTANCE: Enteropathogens were commonly detected in dogs frequenting dog parks, and infection with Giardia correlated with fecal consistency. PCR detection of Giardia had limited diagnostic utility, and detection of Giardia cysts by microscopic technique can vary among laboratories.",2016 Nov 11 Nov-Dec,"['Hascall, K.L.', 'Kass, P.H.', 'Saksen, J.', 'Ahlmann, A.', 'Scorza, A.V.', 'Lappin, M.R.', 'Marks, S.L.']",J Vet Intern Med,,,False
bc101958fdf11b70a365b4de2cbcb5b1d937014b,PMC,Prevalence of Enteropathogens in Dogs Attending 3 Regional Dog Parks in Northern California,http://dx.doi.org/10.1111/jvim.14603,PMC5115183,27859745,CC BY-NC,"BACKGROUND: The prevalence and risk factors for infection with enteropathogens in dogs frequenting dog parks have been poorly documented, and infected dogs can pose a potential zoonotic risk for owners. HYPOTHESIS/OBJECTIVES: To determine the prevalence and risk factors of infection with enteropathogens and zoonotic Giardia strains in dogs attending dog parks in Northern California and to compare results of fecal flotation procedures performed at a commercial and university parasitology laboratory. ANIMALS: Three‐hundred dogs attending 3 regional dog parks in Northern California. METHODS: Prospective study. Fresh fecal specimens were collected from all dogs, scored for consistency, and owners completed a questionnaire. Specimens were analyzed by fecal centrifugation flotation, DFA, and PCR for detection of 11 enteropathogens. Giardia genotyping was performed for assemblage determination. RESULTS: Enteropathogens were detected in 114/300 dogs (38%), of which 62 (54%) did not have diarrhea. Frequency of dog park attendance correlated significantly with fecal consistency (P = .0039), but did not correlate with enteropathogen detection. Twenty‐seven dogs (9%) were infected with Giardia, and genotyping revealed nonzoonotic assemblages C and D. The frequency of Giardia detection on fecal flotation was significantly lower at the commercial laboratory versus the university laboratory (P = .013), and PCR for Giardia was negative in 11/27 dogs (41%) that were positive on fecal flotation or DFA. CONCLUSIONS AND CLINICAL IMPORTANCE: Enteropathogens were commonly detected in dogs frequenting dog parks, and infection with Giardia correlated with fecal consistency. PCR detection of Giardia had limited diagnostic utility, and detection of Giardia cysts by microscopic technique can vary among laboratories.",2016 Nov 11 Nov-Dec,"['Hascall, K.L.', 'Kass, P.H.', 'Saksen, J.', 'Ahlmann, A.', 'Scorza, A.V.', 'Lappin, M.R.', 'Marks, S.L.']",J Vet Intern Med,,,False
69c90ff3190bf937665a71188f2abcd239b2ed06,PMC,Prevalence of Enteropathogens in Dogs Attending 3 Regional Dog Parks in Northern California,http://dx.doi.org/10.1111/jvim.14603,PMC5115183,27859745,CC BY-NC,"BACKGROUND: The prevalence and risk factors for infection with enteropathogens in dogs frequenting dog parks have been poorly documented, and infected dogs can pose a potential zoonotic risk for owners. HYPOTHESIS/OBJECTIVES: To determine the prevalence and risk factors of infection with enteropathogens and zoonotic Giardia strains in dogs attending dog parks in Northern California and to compare results of fecal flotation procedures performed at a commercial and university parasitology laboratory. ANIMALS: Three‐hundred dogs attending 3 regional dog parks in Northern California. METHODS: Prospective study. Fresh fecal specimens were collected from all dogs, scored for consistency, and owners completed a questionnaire. Specimens were analyzed by fecal centrifugation flotation, DFA, and PCR for detection of 11 enteropathogens. Giardia genotyping was performed for assemblage determination. RESULTS: Enteropathogens were detected in 114/300 dogs (38%), of which 62 (54%) did not have diarrhea. Frequency of dog park attendance correlated significantly with fecal consistency (P = .0039), but did not correlate with enteropathogen detection. Twenty‐seven dogs (9%) were infected with Giardia, and genotyping revealed nonzoonotic assemblages C and D. The frequency of Giardia detection on fecal flotation was significantly lower at the commercial laboratory versus the university laboratory (P = .013), and PCR for Giardia was negative in 11/27 dogs (41%) that were positive on fecal flotation or DFA. CONCLUSIONS AND CLINICAL IMPORTANCE: Enteropathogens were commonly detected in dogs frequenting dog parks, and infection with Giardia correlated with fecal consistency. PCR detection of Giardia had limited diagnostic utility, and detection of Giardia cysts by microscopic technique can vary among laboratories.",2016 Nov 11 Nov-Dec,"['Hascall, K.L.', 'Kass, P.H.', 'Saksen, J.', 'Ahlmann, A.', 'Scorza, A.V.', 'Lappin, M.R.', 'Marks, S.L.']",J Vet Intern Med,,,False
f318f417880d9beb2ce5c8444f3597a8808eae30,PMC,"Hepatitis B virus upregulates host expression of α-1,2-mannosidases via the PPARα pathway",http://dx.doi.org/10.3748/wjg.v22.i43.9534,PMC5116597,27920474,CC BY-NC,"AIM: To assess the effects of hepatitis B virus (HBV) on the expression of host α-1,2-mannosidases and determine the underlying mechanisms. METHODS: We measured the expression levels of MAN1A1, MAN1A2, MAN1B1, and MAN1C1 in cell lines HepG2.2.15, HepN10, HepAD38 and HepG2 by Western blot. Viral antigens (HBsAg and HBeAg) in the culture medium were measured using the chemiluminescence method. HBV DNA quantification assays were performed using a commercial real-time PCR kit. Protein levels of human liver tissue α-1,2-mannosidases were also evaluated by Western blot. Plasmids containing seven individual viral genes of HBV (PTT22-HBx, PTT22-HBs, PTT22-preS2, PTT22-preS1, PTT22-HBc, PTT22-HBe, and PTT22-HBp) or control plasmids (PTT22-vector) were transfected into HepG2 cells. MK886 (PPARα) and GW9662 (PPARγ) inhibitors were used to explore the effects of HBV on α-1,2-mannosidase expression after the PPARα and PPARγ pathways were blocked. RESULTS: We showed that the expression of α-1,2-mannosidases was higher in stably transfected HBV cells than in controls. The expression levels of α-1,2-mannosidase were higher in AD38 cells than those in ND10 cells, which were in turn greater than those in G2.2.15 cells, and positively correlated with the expression of HBsAg in all the cell lines. Levels of α-1,2-mannosidase in non-tumorous liver tissues of HBV-related HCC patients were also higher than in the tissues from non-HBV-related HCC patients. Moreover, transfecting HepG2 cells with a component of the HBV viral envelope also increased the expression of α-1,2-mannosidases. However, this envelope protein component could not induce MAN1C1 expression in the presence of a PPARα inhibitor, MK886. We also found that MK886 did not affect the expression of MAN1C1 in AD38 cells without tetracycline in the culture medium. This phenomenon was not observed in the case of GW9662. CONCLUSION: Our results indicate that HBV increases the expression of α-mannosidases both in vitro and in vivo via activation of the PPARα pathway by its envelope protein.",2016 Nov 21,"['Hu, Song', 'Jiang, Li-Bin', 'Zou, Xiao-Jing', 'Yi, Wei', 'Tian, De-Ying']",World J Gastroenterol,,,True
2011e171a1664541e88ec5333849781130565135,PMC,Human Coronavirus in the 2014 Winter Season as a Cause of Lower Respiratory Tract Infection,http://dx.doi.org/10.3349/ymj.2017.58.1.174,PMC5122634,27873511,CC BY-NC,"PURPOSE: During the late autumn to winter season (October to December) in the Republic of Korea, respiratory syncytial virus (RSV) is the most common pathogen causing lower respiratory tract infections (LRTIs). Interestingly, in 2014, human coronavirus (HCoV) caused not only upper respiratory infections but also LRTIs more commonly than in other years. Therefore, we sought to determine the epidemiology, clinical characteristics, outcomes, and severity of illnesses associated with HCoV infections at a single center in Korea. MATERIALS AND METHODS: We retrospectively identified patients with positive HCoV respiratory specimens between October 2014 and December 2014 who were admitted to Severance Children’s Hospital at Yonsei University Medical Center for LRTI. Charts of the patients with HCoV infection were reviewed and compared with RSV infection. RESULTS: During the study period, HCoV was the third most common respiratory virus and accounted for 13.7% of infections. Coinfection was detected in 43.8% of children with HCoV. Interestingly, one patient had both HCoV-OC43 and HCoV-NL63. Mild pneumonia was most common (60.4%) with HCoV, and when combined with RSV, resulted in bronchiolitis. Two patients required care in the intensive care unit. However, compared with that of RSV infection, the disease course HCoV was short. CONCLUSION: Infections caused by HCoVs are common, and can cause LRTIs. During an epidemic season, clinicians should be given special consideration thereto. When combined with other medical conditions, such as neurologic or cardiologic diseases, intensive care unit (ICU) care may be necessary.",2017 Jan 1,"['Kim, Kyu Yeun', 'Han, Song Yi', 'Kim, Ho-Seong', 'Cheong, Hyang-Min', 'Kim, Sung Soon', 'Kim, Dong Soo']",Yonsei Med J,,,True
363b1631ca140d28ca1ba79883e8b339c8a4a68a,PMC,Development and Implementation of Evidence-Based Practice in Cancer Care: Challenges and Opportunities,http://dx.doi.org/10.4103/2347-5625.178168,PMC5123540,27981134,CC BY-NC-SA,"The cancer burden is a global problem, and oncology nurses should be accountable for delivering safe and effective cancer care and providing the best possible experience for patients. The development and application of evidence-based practice in cancer care is an effective strategy in achieving this goal; however, the journey in which such practice involves may encounter various challenges. In this article, the author discusses her own experience, successful and unsuccessful of such a journey. Both challenges and opportunities are identified, and suggestions put forward for making collaborative efforts.",2016 Jan-Mar,"So, Winnie K. W.",Asia Pac J Oncol Nurs,,,True
18aa64efcaae5cb9d066ae197e88b8fce7d15b7a,PMC,IDO-orchestrated crosstalk between pDCs and Tregs inhibits autoimmunity,http://dx.doi.org/10.1016/j.jaut.2016.07.004,PMC5127883,27470005,CC BY-NC-ND,"Plasmacytoid dendritic cells (pDCs) have been shown to both mediate and prevent autoimmunity, and the regulation of their immunogenic versus tolerogenic functions remains incompletely understood. Here we demonstrate that, compared to other cells, pDCs are the major expressors of Indoleamine-2,3-dioxygenase (IDO) in steady-state lymph nodes (LNs). IDO expression by LN pDCs was closely dependent on MHCII-mediated, antigen-dependent, interactions with Treg. We further established that IDO production by pDCs was necessary to confer suppressive function to Tregs. During EAE development, IDO expression by pDCs was required for the generation of Tregs capable of dampening the priming of encephalitogenic T cell and disease severity. Thus, we describe a novel crosstalk between pDCs and Tregs: Tregs shape tolerogenic functions of pDCs prior to inflammation, such that pDCs in turn, promote Treg suppressive functions during autoimmunity.",2016 Dec,"['Lippens, Carla', 'Duraes, Fernanda V.', 'Dubrot, Juan', 'Brighouse, Dale', 'Lacroix, Mathilde', 'Irla, Magali', 'Aubry-Lachainaye, Jean-Pierre', 'Reith, Walter', 'Mandl, Judith N.', 'Hugues, Stéphanie']",J Autoimmun,,,False
1430ebabc4bb953366b635cd4a8adf9956c2f86b,PMC,"The Epidemiology of Hand, Foot and Mouth Disease in Asia: A Systematic Review and Analysis",http://dx.doi.org/10.1097/INF.0000000000001242,PMC5130063,27273688,CC BY-NC-ND,"CONTEXT: Hand, foot and mouth disease (HFMD) is a widespread pediatric disease caused primarily by human enterovirus 71 (EV-A71) and Coxsackievirus A16 (CV-A16). OBJECTIVE: This study reports a systematic review of the epidemiology of HFMD in Asia. DATA SOURCES: PubMed, Web of Science and Google Scholar were searched up to December 2014. STUDY SELECTION: Two reviewers independently assessed studies for epidemiologic and serologic information about prevalence and incidence of HFMD against predetermined inclusion/exclusion criteria. DATA EXTRACTION: Two reviewers extracted answers for 8 specific research questions on HFMD epidemiology. The results are checked by 3 others. RESULTS: HFMD is found to be seasonal in temperate Asia with a summer peak and in subtropical Asia with spring and fall peaks, but not in tropical Asia; evidence of a climatic role was identified for temperate Japan. Risk factors for HFMD include hygiene, age, gender and social contacts, but most studies were underpowered to adjust rigorously for confounding variables. Both community-level and school-level transmission have been implicated, but their relative importance for HFMD is inconclusive. Epidemiologic indices are poorly understood: No supporting quantitative evidence was found for the incubation period of EV-A71; the symptomatic rate of EV-A71/Coxsackievirus A16 infection was from 10% to 71% in 4 studies; while the basic reproduction number was between 1.1 and 5.5 in 3 studies. The uncertainty in these estimates inhibits their use for further analysis. LIMITATIONS: Diversity of study designs complicates attempts to identify features of HFMD epidemiology. CONCLUSIONS: Knowledge on HFMD remains insufficient to guide interventions such as the incorporation of an EV-A71 vaccine in pediatric vaccination schedules. Research is urgently needed to fill these gaps.",2016 Oct 3,"['Koh, Wee Ming', 'Bogich, Tiffany', 'Siegel, Karen', 'Jin, Jing', 'Chong, Elizabeth Y.', 'Tan, Chong Yew', 'Chen, Mark IC', 'Horby, Peter', 'Cook, Alex R.']",Pediatr Infect Dis J,,,True
e3169377d59bbef414c6f7e4b2b36ef7f65e2b1a,PMC,One Health research and training and government support for One Health in South Asia,http://dx.doi.org/10.3402/iee.v6.33842,PMC5131453,27906123,CC BY-NC,"INTRODUCTION: Considerable advocacy, funding, training, and technical support have been provided to South Asian countries to strengthen One Health (OH) collaborative approaches for controlling diseases with global human pandemic potential since the early 2000s. It is essential that the OH approach continues to be strengthened given South Asia is a hot spot for emerging and endemic zoonotic diseases. The objectives of this article are to describe OH research and training and capacity building activities and the important developments in government support for OH in these countries to identify current achievements and gaps. MATERIALS AND METHODS: A landscape analysis of OH research, training, and government support in South Asia was generated by searching peer-reviewed and grey literature for OH research publications and reports, a questionnaire survey of people potentially engaged in OH research in South Asia and the authors’ professional networks. RESULTS: Only a small proportion of zoonotic disease research conducted in South Asia can be described as truly OH, with a significant lack of OH policy-relevant research. A small number of multisectoral OH research and OH capacity building programmes were conducted in the region. The governments of Bangladesh and Bhutan have established operational OH strategies, with variable progress institutionalising OH in other countries. Identified gaps were a lack of useful scientific information and of a collaborative culture for formulating and implementing integrated zoonotic disease control policies and the need for ongoing support for transdisciplinary OH research and policy-relevant capacity building programmes. DISCUSSION: Overall we found a very small number of truly OH research and capacity building programmes in South Asia. Even though significant progress has been made in institutionalising OH in some South Asian countries, further behavioural, attitudinal, and institutional changes are required to strengthen OH research and training and implementation of sustainably effective integrated zoonotic disease control policies.",2016 Nov 29,"['McKenzie, Joanna S.', 'Dahal, Rojan', 'Kakkar, Manish', 'Debnath, Nitish', 'Rahman, Mahmudur', 'Dorjee, Sithar', 'Naeem, Khalid', 'Wijayathilaka, Tikiri', 'Sharma, Barun Kumar', 'Maidanwal, Nasir', 'Halimi, Asmatullah', 'Kim, Eunmi', 'Chatterjee, Pranab', 'Devleesschauwer, Brecht']",Infect Ecol Epidemiol,,,True
fc1d9acb5bb63e3a7898b27d287ff5862b4f2b09,PMC,One Health in China,http://dx.doi.org/10.3402/iee.v6.33843,PMC5131455,27906124,CC BY-NC,"As a result of rapid economic growth over the previous three decades, China has become the second largest economy worldwide since 2010. However, as a developing country with the largest population, this rapid economic growth primarily based on excessive consumption and waste of resources. Thus, China has been facing particularly severe ecological and environmental problems in speeding up industrialization and urbanization. The impact of the health risk factors is complex and difficult to accurately predict. Therefore, it is critical to investigate potential threats in the context of the human-animal-environment interface to protect human and animal health. The “One Health” concept recognizes that human health is connected to animal and environmental health. This review primarily discusses specific health problems in China, particularly zoonoses, and explains the origin and development of the One Health approach, as well as the importance of a holistic approach in China.",2016 Nov 29,"['Wu, Jianyong', 'Liu, Lanlan', 'Wang, Guoling', 'Lu, Jiahai']",Infect Ecol Epidemiol,,,True
dd5267fbf9f6d0890db801e94fa7f0612d11bb18,PMC,Valuable hematological indicators for the diagnosis and severity assessment of Chinese children with community-acquired pneumonia: Prealbumin,http://dx.doi.org/10.1097/MD.0000000000005452,PMC5134884,27893691,CC BY-NC-ND,"Chest X-ray is a “golden standard” for the diagnosis and severity assessment of community-acquired pneumonia (CAP). However, it cannot be used as routine examination of CAP in children. The present study aims to investigate the roles of prealbumin (PA) in CAP in children and further determine the usefulness of PA in diagnosis and severity assessment of CAP in children. This was a retrospective analysis of 174 cases of hospitalized children with CAP. The following indicators were recorded: vital sign, inflammatory indexes, PA, and respiratory pathogens immunoglobulin M antibody test results. A total of 33 healthy children were selected as the control group. The results of laboratory tests between CAP and control groups were compared. CAP group was further divided into mild CAP and severe CAP groups, and vital signs and laboratory examination results of 2 groups were compared. The total positive rate of Mycoplasma pneumoniae in this study was 27.4%, and there was no significant difference in different seasons (P = 0.356). Compared with controls, there was no significant difference between procalcitonin and C-reactive protein in CAP group (P = 0.355, 0.061). The white blood cell count, percentage of neutrophils, neutrophil count, and erythrocyte sedimentation rate in the CAP group were significantly higher than those in control group, and PA was significantly lower than that in the control group (all P < 0.05). In the traditional cutoff value (<170 mg/L), the sensitivity of PA for the diagnosis of CAP was 0.847, which was significant higher than traditional inflammatory indicators. Moreover, it was found that PA was an independent protective factor for CAP in children based on multivariate analysis (odds ratio: 0.974; 95% confidence interval: 0.956–0.993; P = 0.008). PA level in severe CAP group was significantly lower than in mild CAP group (P = 0.001). With a cutoff value of 125 mg/L, the sensitivity and specificity of PA for the severity assessment of CAP were 0.703 and 0.714, respectively. Combined with traditional inflammatory markers, PA may improve the diagnostic efficacy of CAP in children. PA can be used as a reference marker to complement the chest X-rays for severity assessment of children CAP.",2016 Nov 28,"['Ning, Jingjing', 'Shao, Xiaonan', 'Ma, Yibo', 'Lv, Darong']",Medicine (Baltimore),,,True
926408598f7ddf6bf47220216c711797f1c41825,PMC,Fulminant ecchymosis as the initial manifestation of antiphospholipid syndrome (APS) triggered by respiratory syncytial virus (RSV) infection: A case report and review of the literature,http://dx.doi.org/10.1016/j.idcr.2016.10.013,PMC5137331,27920986,CC BY-NC-ND,"We present a unique and informative instance of respiratory syncytial virus (RSV) infection associated with antiphospholipid syndrome (APS), and discuss this case in the context of the literature addressing the immunopathogenesis of APS associated with diverse infections. We describe the case of a 43-year-old man with no significant past medical history who presented with the acute onset of fever, hemoptysis, and extensive bullous, ecchymotic lesions in both lower extremities. Punch biopsy of the lesion demonstrated thrombotic vasculopathy. Further evaluation revealed serum antiphospholipid antibodies as well as a positive RSV PCR in a nasal swab specimen. Clinical manifestations, positive laboratory and pathological findings were strongly suggestive of APS associated with a recent RSV infection. When an infectious etiology is considered for APS, RSV should also be included in the differential diagnosis.",2016 Nov 24,"['Makino, Jun', 'Koshy, Sanjana', 'Bajaj, Sonal', 'Jeong, Young-Gwang', 'Perlman, David C.']",IDCases,,,False
fc97aeb066cf1151c61d37d9bdce776463d9fbc4,PMC,Detection of kobuvirus RNA in Japanese domestic dogs,http://dx.doi.org/10.1292/jvms.16-0217,PMC5138431,27488907,CC BY-NC-ND,"To investigate whether kokuvirus is present in Japanese dogs, we examined the fecal samples obtained from 94 diarrheal household dogs and 50 clinically healthy kenneled dogs by RT-PCR. The gene was detected in 37.2% and 48.0% in the former and the latter, respectively, suggesting that canine kobuvirus (CaKoV) is circulating among Japanese dogs. From the result of the latter, however, CaKoV may not be a primary pathogen. Furthermore, all gene-positive dogs were purebreds aged four months or younger. This finding suggests that CaKoV endemic is confined in multi-dog environments, and the dogs have a strong age-dependent resistance to CaKoV.",2016 Nov 2,"['SOMA, Takehisa', 'MATSUBAYASHI, Makoto', 'SASAI, Kazumi']",J Vet Med Sci,,,True
40f79b91682886f0f531b6bb876482a23cd6e400,PMC,Differential Cell Count and CRP Level in Blood as Predictors for Middle East Respiratory Syndrome Coronavirus Infection in Acute Febrile Patients during Nosocomial Outbreak,http://dx.doi.org/10.3346/jkms.2017.32.1.151,PMC5143288,27914145,CC BY-NC,A case-control study was performed to identify clinical predictors for Middle East respiratory syndrome coronavirus (MERS-CoV) infection among patients with acute febrile illness during the nosocomial outbreak. Patients with MERS-CoV were more likely to have monocytosis with normal white blood cell (WBC) count and lower C-reactive protein (CRP) level. Simple laboratory data such as complete blood counts (CBC) with differential count could be a useful marker for the prediction of MERS and triage at the initial presentation of acute febrile patients in outbreak setting.,2017 Jan 11,"['Park, Ga Eun', 'Kang, Cheol-In', 'Ko, Jae-Hoon', 'Cho, Sun Young', 'Ha, Young Eun', 'Kim, Yae-Jean', 'Peck, Kyong Ran', 'Song, Jae-Hoon', 'Chung, Doo Ryeon']",J Korean Med Sci,,,True
b66704a03a688c4065abff41c4977c4c9939c230,PMC,"Lobeglitazone, a Novel Thiazolidinedione, Improves Non-Alcoholic Fatty Liver Disease in Type 2 Diabetes: Its Efficacy and Predictive Factors Related to Responsiveness",http://dx.doi.org/10.3346/jkms.2017.32.1.60,PMC5143300,27914133,CC BY-NC,"Despite the rapidly increasing prevalence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes (T2D), few treatment modalities are currently available. We investigated the hepatic effects of the novel thiazolidinedione (TZDs), lobeglitazone (Duvie) in T2D patients with NAFLD. We recruited drug-naïve or metformin-treated T2D patients with NAFLD to conduct a multicenter, prospective, open-label, exploratory clinical trial. Transient liver elastography (Fibroscan(®); Echosens, Paris, France) with controlled attenuation parameter (CAP) was used to non-invasively quantify hepatic fat contents. Fifty patients with CAP values above 250 dB/m were treated once daily with 0.5 mg lobeglitazone for 24 weeks. The primary endpoint was a decline in CAP values, and secondary endpoints included changes in components of glycemic, lipid, and liver profiles. Lobeglitazone-treated patients showed significantly decreased CAP values (313.4 dB/m at baseline vs. 297.8 dB/m at 24 weeks; P = 0.016), regardless of glycemic control. Lobeglitazone improved HbA(1C) values (7.41% [57.5 mM] vs. 6.56% [48.2 mM]; P < 0.001), as well as the lipid and liver profiles of the treated patients. Moreover, multivariable linear regression analysis showed that hepatic fat reduction by lobeglitazone was independently associated with baseline values of CAP, liver stiffness, and liver enzymes, and metformin use. Lobeglitazone treatment reduced intrahepatic fat content, as assessed by transient liver elastography, and improved glycemic, liver, and lipid profiles in T2D patients with NAFLD. Further randomized controlled trials using liver histology as an end point are necessary to evaluate the efficacy of lobeglitazone for NAFLD treatment (Clinical trial No. NCT02285205).",2017 Jan 8,"['Lee, Yong-ho', 'Kim, Jae Hyeon', 'Kim, So Ra', 'Jin, Heung Yong', 'Rhee, Eun-Jung', 'Cho, Young Min', 'Lee, Byung-Wan']",J Korean Med Sci,,,True
6d59ebd9375d41f107b221988db5081f4c20d8c1,PMC,Role of cardiac renin angiotensin system in ischemia reperfusion injury and preconditioning of heart,http://dx.doi.org/10.1016/j.ihj.2016.06.010,PMC5143827,27931559,CC BY-NC-ND,"Cardio-vascular diseases are the leading cause of morbidity and mortality. Ischemia is a state of oxygen deprivation in tissues, whereas reperfusion is restoration of blood flow in ischemic tissues. Myocardial damage of tissue during reperfusion after ischemic insult is known as myocardial ischemia–reperfusion (I/R) injury. It induces damage to cardiac muscle via increasing expression of oxygen, sodium and calcium ions which are responsible in the activation of proteases and cell death. Heart renin angiotensin system (RAS) plays an important role in the myocardial ischemia and reperfusion injury. Angiotensin (1–7) is responsible for vasodilation and angiotensin II for vasoconstriction. Here-in we reviewed how myocardial I/R injury sets in by up-regulation of angiotensin II that leads to increased infarct size, which can be reduced by the use of ACE inhibitors, ACE2 activators and angiotensin II antagonist.",2016 Aug 29 Nov-Dec,"['Agrawal, Vimal', 'Gupta, Jeetendra Kumar', 'Qureshi, Shaiba Sana', 'Vishwakarma, Vishal Kumar']",Indian Heart J,,,False
09e6d442b7da6f36e3c7a82a056d8d61e27b1050,PMC,Capture-stabilize approach for membrane protein SPR assays,http://dx.doi.org/10.1038/srep07360,PMC5154539,25484112,CC BY-NC-ND,"Measuring the binding kinetics of antibodies to intact membrane proteins by surface plasmon resonance has been challenging largely because of the inherent difficulties in capturing membrane proteins on chip surfaces while retaining their native conformation. Here we describe a method in which His-tagged CXCR5, a GPCR, was purified and captured on a Biacore chip surface via the affinity tag. The captured receptor protein was then stabilized on the chip surface by limited cross-linking. The resulting chip surface retained ligand binding activity and was used for monoclonal antibody kinetics assays by a standard Biacore kinetics assay method with a simple low pH regeneration step. We demonstrate the advantages of this whole receptor assay when compared to available peptide-based binding assays. We further extended the application of the capture-stabilize approach to virus-like particles and demonstrated its utility analyzing antibodies against CD52, a GPI-anchored protein, in its native membrane environment. The results are the first demonstration of chemically stabilized chip surfaces for membrane protein SPR assays.",2014 Dec 8,"['Chu, Ruiyin', 'Reczek, David', 'Brondyk, William']",Sci Rep,,,True
c4bffc76026b935fe454f98878510ab490e75bff,PMC,ALV-J strain SCAU-HN06 induces innate immune responses in chicken primary monocyte-derived macrophages,http://dx.doi.org/10.3382/ps/pew229,PMC5161024,27486255,CC BY-NC,"Avian leucosis virus subgroup J (ALV-J) can cause lifelong infection and can escape from the host immune defenses in chickens. Since macrophages act as the important defense line against invading pathogens in host innate immunity, we investigated the function and innate immune responses of chicken primary monocyte-derived macrophages (MDM) after ALV-J infection in this study. Our results indicated that ALV-J was stably maintained in MDM cells but that the viral growth rate was significantly lower than that in DF-1 cells. We also found that ALV-J infection significantly increased nitric oxide (NO) production, but had no effect on MDM phagocytic capacity. Interestingly, infection with ALV-J rapidly promoted the expression levels of Myxovirus resistance 1 (Mx) (3 h, 6 h), ISG12 (6 h), and interleukin-1β (IL-1β) (3 h, 12 h) at an early infection stage, whereas it sharply decreased the expression of Mx (24 h, 36 h), ISG12 (36 h), and made little change on IL-1β (24 h, 36 h) production at a late infection stage in MDM cells. Moreover, the protein levels of interferon-β (IFN-β) and interleukin-6 (IL-6) had sharply increased in infected MDM cells from 3 to 36 h post infection (hpi) of ALV-J. And, the protein level of interleukin-10 (IL-10) was dramatically decreased at 36 hpi in MDM cells infected with ALV-J. These results demonstrate that ALV-J can induce host innate immune responses and we hypothesize that macrophages play an important role in host innate immune attack and ALV-J immune escape.",2017 Jan 2,"['Feng, Min', 'Dai, Manman', 'Cao, Weisheng', 'Tan, Yan', 'Li, Zhenhui', 'Shi, Meiqing', 'Zhang, Xiquan']",Poult Sci,,,True
1e028783dd3a8a7dca6ee99c21277471571b4e1d,PMC,Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons,http://dx.doi.org/10.1016/j.ebiom.2016.11.017,PMC5161441,27884655,CC BY-NC-ND,"BACKGROUND: Disseminated or fatal Zika virus (ZIKV) infections were reported in immunosuppressed patients. Existing interferon-signaling/receptor-deficient mouse models may not be suitable for evaluating treatment effects of recombinant interferons. METHODS: We developed a novel mouse model for ZIKV infection by immunosuppressing BALB/c mice with dexamethasone. RESULTS: Dexamethasone-immunosuppressed male mice (6–8 weeks) developed disseminated infection as evidenced by the detection of ZIKV-NS1 protein expression and high viral loads in multiple organs. They had ≥ 10% weight loss and high clinical scores soon after dexamethasone withdrawal (10 dpi), which warranted euthanasia at 12 dpi. Viral loads in blood and most tissues at 5 dpi were significantly higher than those at 12 dpi (P < 0.05). Histological examination revealed prominent inflammatory infiltrates in multiple organs, and CD45 + and CD8 + inflammatory cells were seen in the testis. These findings suggested that clinical deterioration occurred during viral clearance by host immune response. Type I interferon treatments improved clinical outcome of mice (100% vs 0% survival). CONCLUSIONS: Besides virus dissemination, inflammation of various tissues, especially orchitis, may be potential complications of ZIKV infection with significant implications on disease transmission and male fertility. Interferon treatment should be considered in patients at high risks for ZIKV-associated complications when the potential benefits outweigh the side effects of treatment.",2016 Nov 12,"['Chan, Jasper Fuk-Woo', 'Zhang, Anna Jinxia', 'Chan, Chris Chung-Sing', 'Yip, Cyril Chik-Yan', 'Mak, Winger Wing-Nga', 'Zhu, Houshun', 'Poon, Vincent Kwok-Man', 'Tee, Kah-Meng', 'Zhu, Zheng', 'Cai, Jian-Piao', 'Tsang, Jessica Oi-Ling', 'Chik, Kenn Ka-Heng', 'Yin, Feifei', 'Chan, Kwok-Hung', 'Kok, Kin-Hang', 'Jin, Dong-Yan', 'Au-Yeung, Rex Kwok-Him', 'Yuen, Kwok-Yung']",EBioMedicine,,,False
d7df17379b5a79dd5917ea5f26051eef8bfe5011,PMC,Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modeling Study,http://dx.doi.org/10.1016/S0140-6736(16)31838-4,PMC5161610,27837923,CC BY-NC-ND,"BACKGROUND: The ongoing yellow fever (YF) epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa in July–August 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidating the conditions under which dose fractionation would reduce transmission. METHODS: We estimate the effective reproductive number for YF in Angola using disease natural history and case report data. With simple mathematical models of YF transmission, we calculate the infection attack rate (IAR, the proportion of population infected over the course of an epidemic) under varying levels of transmissibility and five-fold fractional-dose vaccine efficacy for two vaccination scenarios: (i) random vaccination in a hypothetical population that is completely susceptible; (ii) the Kinshasa vaccination campaign in July–August 2016 with different age cutoff for fractional-dose vaccines. FINDINGS: We estimate the effective reproductive number early in the Angola outbreak was between 5·2 and 7·1. If vaccine action is all-or-nothing (i.e. a proportion VE of vaccinees receives complete and the remainder receive no protection), n-fold fractionation can dramatically reduce IAR as long as efficacy VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (i.e. the susceptibility of each vaccinee is reduced by a factor that is equal to the vaccine efficacy VE). The age cutoff for fractional-dose vaccines chosen by the WHO for the Kinshasa vaccination campaign (namely, 2 years) provides the largest reduction in IAR if the efficacy of five-fold fractional-dose vaccines exceeds 20%. INTERPRETATION: Dose fractionation is a very effective strategy for reducing infection attack rate that would be robust with a large margin for error in case fractional-dose VE is lower than expected.",2016 Dec 10,"['Wu, Joseph T.', 'Peak, Corey M.', 'Leung, Gabriel M.', 'Lipsitch, Marc']",Lancet,,,True
5bc13185f8fc98b99cd1fb22078afeda41eb1e7e,PMC,Evolution and Variation of the SARS-CoV Genome,http://dx.doi.org/10.1016/S1672-0229(03)01027-1,PMC5172238,15629034,CC BY-NC-ND,"Knowledge of the evolution of pathogens is of great medical and biological significance to the prevention, diagnosis, and therapy of infectious diseases. In order to understand the origin and evolution of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus), we collected complete genome sequences of all viruses available in GenBank, and made comparative analyses with the SARS-CoV. Genomic signature analysis demonstrates that the coronaviruses all take the TGTT as their richest tetranucleotide except the SARS-CoV. A detailed analysis of the forty-two complete SARS-CoV genome sequences revealed the existence of two distinct genotypes, and showed that these isolates could be classified into four groups. Our manual analysis of the BLASTN results demonstrates that the HE (hemagglutinin-esterase) gene exists in the SARS-CoV, and many mutations made it unfamiliar to us.",2003 Aug 28,"['Hu, Jianfei', 'Wang, Jing', 'Xu, Jing', 'Li, Wei', 'Han, Yujun', 'Li, Yan', 'Ji, Jia', 'Ye, Jia', 'Xu, Zhao', 'Zhang, Zizhang', 'Wei, Wei', 'Li, Songgang', 'Wang, Jun', 'Wang, Jian', 'Yu, Jun', 'Yang, Huanming']",Genomics Proteomics Bioinformatics,,,False
6d03f3e2dd6554f15526cb089337fa592fb1834c,PMC,Genome Organization of the SARS-CoV,http://dx.doi.org/10.1016/S1672-0229(03)01028-3,PMC5172239,15629035,CC BY-NC-ND,"Annotation of the genome sequence of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) is indispensable to understand its evolution and pathogenesis. We have performed a full annotation of the SARS-CoV genome sequences by using annotation programs publicly available or developed by ourselves. Totally, 21 open reading frames (ORFs) of genes or putative uncharacterized proteins (PUPs) were predicted. Seven PUPs had not been reported previously, and two of them were predicted to contain transmembrane regions. Eight ORFs partially overlapped with or embedded into those of known genes, revealing that the SARS-CoV genome is a small and compact one with overlapped coding regions. The most striking discovery is that an ORF locates on the minus strand. We have also annotated non-coding regions and identified the transcription regulating sequences (TRS) in the intergenic regions. The analysis of TRS supports the minus strand extending transcription mechanism of coronavirus. The SNP analysis of different isolates reveals that mutations of the sequences do not affect the prediction results of ORFs.",2003 Aug 28,"['Xu, Jing', 'Hu, Jianfei', 'Wang, Jing', 'Han, Yujun', 'Hu, Yongwu', 'Wen, Jie', 'Li, Yan', 'Ji, Jia', 'Ye, Jia', 'Zhang, Zizhang', 'Wei, Wei', 'Li, Songgang', 'Wang, Jun', 'Wang, Jian', 'Yu, Jun', 'Yang, Huanming']",Genomics Proteomics Bioinformatics,,,False
88019c8e3c252aa2f8639aa98dc7afcd554da22c,PMC,The M Protein of SARS-CoV: Basic Structural and Immunological Properties,http://dx.doi.org/10.1016/S1672-0229(03)01016-7,PMC5172243,15626342,CC BY-NC-ND,"We studied structural and immunological properties of the SARS-CoV M (membrane) protein, based on comparative analyses of sequence features, phylogenetic investigation, and experimental results. The M protein is predicted to contain a triple-spanning transmembrane (TM) region, a single N-glycosylation site near its N-terminus that is in the exterior of the virion, and a long C-terminal region in the interior. The M protein harbors a higher substitution rate (0.6% correlated to its size) among viral open reading frames (ORFs) from published data. The four substitutions detected in the M protein, which cause non-synonymous changes, can be classified into three types. One of them results in changes of pI (isoelectric point) and charge, affecting antigenicity. The second changes hydrophobicity of the TM region, and the third one relates to hydrophilicity of the interior structure. Phylogenetic tree building based on the variations of the M protein appears to support the non-human origin of SARS-CoV. To investigate its immunogenicity, we synthesized eight oligopeptides covering 69.2% of the entire ORF and screened them by using ELISA (enzyme-linked immunosorbent assay) with sera from SARS patients. The results confirmed our predictions on antigenic sites.",2003 May 28,"['Hu, Yongwu', 'Wen, Jie', 'Tang, Lin', 'Zhang, Haijun', 'Zhang, Xiaowei', 'Li, Yan', 'Wang, Jing', 'Han, Yujun', 'Li, Guoqing', 'Shi, Jianping', 'Tian, Xiangjun', 'Jiang, Feng', 'Zhao, Xiaoqian', 'Wang, Jun', 'Liu, Siqi', 'Zeng, Changqing', 'Wang, Jian', 'Yang, Huanming']",Genomics Proteomics Bioinformatics,,,False
18afccb280f2109ea8f52981cc172dbaa83de72d,PMC,The R Protein of SARS-CoV: Analyses of Structure and Function Based on Four Complete Genome Sequences of Isolates BJ01-BJ04,http://dx.doi.org/10.1016/S1672-0229(03)01019-2,PMC5172245,15626345,CC BY-NC-ND,"The R (replicase) protein is the uniquely defined non-structural protein (NSP) responsible for RNA replication, mutation rate or fidelity, regulation of transcription in coronaviruses and many other ssRNA viruses. Based on our complete genome sequences of four isolates (BJ01-BJ04) of SARS-CoV from Beijing, China, we analyzed the structure and predicted functions of the R protein in comparison with 13 other isolates of SARS-CoV and 6 other coronaviruses. The entire ORF (open-reading frame) encodes for two major enzyme activities, RNA-dependent RNA polymerase (RdRp) and proteinase activities. The R polyprotein undergoes a complex proteolytic process to produce 15 function-related peptides. A hydrophobic domain (HOD) and a hydrophilic domain (HID) are newly identified within NSP1. The substitution rate of the R protein is close to the average of the SARS-CoV genome. The functional domains in all NSPs of the R protein give different phylogenetic results that suggest their different mutation rate under selective pressure. Eleven highly conserved regions in RdRp and twelve cleavage sites by 3CLP (chymotrypsin-like protein) have been identified as potential drug targets. Findings suggest that it is possible to obtain information about the phylogeny of SARS-CoV, as well as potential tools for drug design, genotyping and diagnostics of SARS.",2003 May 28,"['Xu, Zuyuan', 'Zhang, Haiqing', 'Tian, Xiangjun', 'Ji, Jia', 'Li, Wei', 'Li, Yan', 'Tian, Wei', 'Han, Yujun', 'Wang, Lili', 'Zhang, Zizhang', 'Xu, Jing', 'Wei, Wei', 'Zhu, Jingui', 'Sun, Haiyan', 'Zhang, Xiaowei', 'Zhou, Jun', 'Li, Songgang', 'Wang, Jun', 'Wang, Jian', 'Bi, Shengli', 'Yang, Huanming']",Genomics Proteomics Bioinformatics,,,False
8be5900da085366ee4808713f7e80b3b1a5e67e0,PMC,The Epitope Study on the SARS-CoV Nucleocapsid Protein,http://dx.doi.org/10.1016/S1672-0229(03)01025-8,PMC5172353,15629032,CC BY-NC-ND,"The nucleocapsid protein (N protein) has been found to be an antigenic protein in a number of coronaviruses. Whether the N protein in severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is antigenic remains to be elucidated. Using Western blot and Enzyme-linked Immunosorbent Assay (ELISA), the recombinant N proteins and the synthesized peptides derived from the N protein were screened in sera from SARS patients. All patient sera in this study displayed strong positive immunoreactivities against the recombinant N proteins, whereas normal sera gave negative immunoresponses to these proteins, indicating that the N protein of SARS-CoV is an antigenic protein. Furthermore, the epitope sites in the N protein were determined by competition experiments, in which the recombinant proteins or the synthesized peptides competed against the SARS-CoV proteins to bind to the antibodies raised in SARS sera. One epitope site located at the C-terminus was confirmed as the most antigenic region in this protein. A detailed screening of peptide with ELISA demonstrated that the amino sequence from Codons 371 to 407 was the epitope site at the C-terminus of the N protein. Understanding of the epitope sites could be very significant for developing an effective diagnostic approach to SARS.",2003 Aug 28,"['Li, Shuting', 'Lin, Liang', 'Wang, Hao', 'Yin, Jianning', 'Ren, Yan', 'Zhao, Zhe', 'Wen, Jie', 'Zhou, Cuiqi', 'Zhang, Xumin', 'Li, Xiaolei', 'Wang, Jingqiang', 'Zhou, Zhengfeng', 'Liu, Jinxiu', 'Shao, Jianmin', 'Lei, Tingting', 'Fang, Jianqiu', 'Xu, Ningzhi', 'Liu, Siqi']",Genomics Proteomics Bioinformatics,,,False
9d217a6fc11fb8754ebceb07d07c0b84175191ce,PMC,The Structural Characterization and Antigenicity of the S Protein of SARS-CoV,http://dx.doi.org/10.1016/S1672-0229(03)01015-5,PMC5172354,15626341,CC BY-NC-ND,"The corona-like spikes or peplomers on the surface of the virion under electronic microscope are the most striking features of coronaviruses. The S (spike) protein is the largest structural protein, with 1,255 amino acids, in the viral genome. Its structure can be divided into three regions: a long N-terminal region in the exterior, a characteristic transmembrane (TM) region, and a short C-terminus in the interior of a virion. We detected fifteen substitutions of nucleotides by comparisons with the seventeen published SARS-CoV genome sequences, eight (53.3%) of which are non-synonymous mutations leading to amino acid alternations with predicted physiochemical changes. The possible antigenic determinants of the S protein are predicted, and the result is confirmed by ELISA (enzyme-linked immunosorbent assay) with synthesized peptides. Another profound finding is that three disulfide bonds are defined at the C-terminus with the N-terminus of the E (envelope) protein, based on the typical sequence and positions, thus establishing the structural connection with these two important structural proteins, if confirmed. Phylogenetic analysis reveals several conserved regions that might be potent drug targets.",2003 May 28,"['Li, Jingxiang', 'Luo, Chunqing', 'Deng, Yajun', 'Han, Yujun', 'Tang, Lin', 'Wang, Jing', 'Ji, Jia', 'Ye, Jia', 'Jiang, Fanbo', 'Xu, Zhao', 'Tong, Wei', 'Wei, Wei', 'Zhang, Qingrun', 'Li, Shengbin', 'Li, Wei', 'Li, Hongyan', 'Li, Yudong', 'Dong, Wei', 'Wang, Jian', 'Bi, Shengli', 'Yang, Huanming']",Genomics Proteomics Bioinformatics,,,False
55461f69aec24f255e9bbdda2e286e08c4999510,PMC,A Strategy for Searching Antigenic Regions in the SARS-CoV Spike Protein,http://dx.doi.org/10.1016/S1672-0229(03)01026-X,PMC5172407,15629033,CC BY-NC-ND,"In the face of the worldwide threat of severe acute respiratory syndrome (SARS) to human life, some of the most urgent challenges are to develop fast and accurate analytical methods for early diagnosis of this disease as well as to create a safe anti-viral vaccine for prevention. To these ends, we investigated the antigenicity of the spike protein (S protein), a major structural protein in the SARS-coronavirus (SARS-CoV). Based upon the theoretical analysis for hydrophobicity of the S protein, 18 peptides were synthesized. Using Enzyme-Linked Immunosorbent Assay (ELISA), these peptides were screened in the sera from SARS patients. According to these results, two fragments of the S gene were amplified by PCR and cloned into pET-32a. Both S fragments were expressed in the BL-21 strain and further purified with an affinity chromatography. These recombinant S fragments were confirmed to have positive cross-reactions with SARS sera, either by Western blot or by ELISA. Our results demonstrated that the potential epitope regions were located at Codons 469–882 in the S protein, and one epitope site was located at Codons 599–620. Identification of antigenic regions in the SARS-CoV S protein may be important for the functional studies of this virus or the development of clinical diagnosis.",2003 Aug 28,"['Ren, Yan', 'Zhou, Zhengfeng', 'Liu, Jinxiu', 'Lin, Liang', 'Li, Shuting', 'Wang, Hao', 'Xia, Ji', 'Zhao, Zhe', 'Wen, Jie', 'Zhou, Cuiqi', 'Wang, Jingqiang', 'Yin, Jianning', 'Xu, Ningzhi', 'Liu, Siqi']",Genomics Proteomics Bioinformatics,,,False
92eaf000df8d90ca6aacf8d56ec4bb2037fd3545,PMC,"A Genome Sequence of Novel SARS-CoV Isolates: the Genotype, GD-Ins29, Leads to a Hypothesis of Viral Transmission in South China",http://dx.doi.org/10.1016/S1672-0229(03)01014-3,PMC5172408,15626340,CC BY-NC-ND,"We report a complete genomic sequence of rare isolates (minor genotype) of the SARS-CoV from SARS patients in Guangdong, China, where the first few cases emerged. The most striking discovery from the isolate is an extra 29-nucleotide sequence located at the nucleotide positions between 27,863 and 27,864 (referred to the complete sequence of BJ01) within an overlapped region composed of BGI-PUP5 (BGI-postulated uncharacterized protein 5) and BGI-PUP6 upstream of the N (nucleocapsid) protein. The discovery of this minor genotype, GD-Ins29, suggests a significant genetic event and differentiates it from the previously reported genotype, the dominant form among all sequenced SARS-CoV isolates. A 17-nt segment of this extra sequence is identical to a segment of the same size in two human mRNA sequences that may interfere with viral genome replication and transcription in the cytosol of the infected cells. It provides a new avenue for the exploration of the virus-host interaction in viral evolution, host pathogenesis, and vaccine development.",2003 May 28,"['Qin, E’de', 'He, Xionglei', 'Tian, Wei', 'Liu, Yong', 'Li, Wei', 'Wen, Jie', 'Wang, Jingqiang', 'Fan, Baochang', 'Wu, Qingfa', 'Chang, Guohui', 'Cao, Wuchun', 'Xu, Zuyuan', 'Yang, Ruifu', 'Wang, Jing', 'Yu, Man', 'Li, Yan', 'Xu, Jing', 'Si, Bingyin', 'Hu, Yongwu', 'Peng, Wenming', 'Tang, Lin', 'Jiang, Tao', 'Shi, Jianping', 'Ji, Jia', 'Zhang, Yu', 'Ye, Jia', 'Wang, Cui’e', 'Han, Yujun', 'Zhou, Jun', 'Deng, Yajun', 'Li, Xiaoyu', 'Hu, Jianfei', 'Wang, Caiping', 'Yan, Chunxia', 'Zhang, Qingrun', 'Bao, Jingyue', 'Li, Guoqing', 'Chen, Weijun', 'Fang, Lin', 'Li, Changfeng', 'Lei, Meng', 'Li, Dawei', 'Tong, Wei', 'Tian, Xiangjun', 'Wang, Jin', 'Zhang, Bo', 'Zhang, Haiqing', 'Zhang, Yilin', 'Zhao, Hui', 'Zhang, Xiaowei', 'Li, Shuangli', 'Cheng, Xiaojie', 'Zhang, Xiuqing', 'Liu, Bin', 'Zeng, Changqing', 'Li, Songgang', 'Tan, Xuehai', 'Liu, Siqi', 'Dong, Wei', 'Wang, Jun', 'Wong, Gane Ka-Shu', 'Yu, Jun', 'Wang, Jian', 'Zhu, Qingyu', 'Yang, Huanming']",Genomics Proteomics Bioinformatics,,,False
82e80640af0a98cc07c911c9476f693c5e9a62cf,PMC,Complete Genome Sequences of the SARS-CoV: the BJ Group (Isolates BJ01-BJ04),http://dx.doi.org/10.1016/S1672-0229(03)01023-4,PMC5172409,15629030,CC BY-NC-ND,"Beijing has been one of the epicenters attacked most severely by the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) since the first patient was diagnosed in one of the city’s hospitals. We now report complete genome sequences of the BJ Group, including four isolates (Isolates BJ01, BJ02, BJ03, and BJ04) of the SARS-CoV. It is remarkable that all members of the BJ Group share a common haplotype, consisting of seven loci that differentiate the group from other isolates published to date. Among 42 substitutions uniquely identified from the BJ group, 32 are non-synonymous changes at the amino acid level. Rooted phylogenetic trees, proposed on the basis of haplotypes and other sequence variations of SARS-CoV isolates from Canada, USA, Singapore, and China, gave rise to different paradigms but positioned the BJ Group, together with the newly discovered GD01 (GD-Ins29) in the same clade, followed by the H-U Group (from Hong Kong to USA) and the H-T Group (from Hong Kong to Toronto), leaving the SP Group (Singapore) more distant. This result appears to suggest a possible transmission path from Guangdong to Beijing/Hong Kong, then to other countries and regions.",2003 Aug 28,"['Bi, Shengli', 'Qin, E’de', 'Xu, Zuyuan', 'Li, Wei', 'Wang, Jing', 'Hu, Yongwu', 'Liu, Yong', 'Duan, Shumin', 'Hu, Jianfei', 'Han, Yujun', 'Xu, Jing', 'Li, Yan', 'Yi, Yao', 'Zhou, Yongdong', 'Lin, Wei', 'Wen, Jie', 'Xu, Hong', 'Li, Ruan', 'Zhang, Zizhang', 'Sun, Haiyan', 'Zhu, Jingui', 'Yu, Man', 'Fan, Baochang', 'Wu, Qingfa', 'Lin, Wei', 'Tang, Lin', 'Yang, Bao’an', 'Li, Guoqing', 'Peng, Wenming', 'Li, Wenjie', 'Jiang, Tao', 'Deng, Yajun', 'Liu, Bohua', 'Shi, Jianping', 'Deng, Yongqiang', 'Wei, Wei', 'Liu, Hong', 'Tong, Zongzhong', 'Zhang, Feng', 'Zhang, Yu', 'Wang, Cui’e', 'Li, Yuquan', 'Ye, Jia', 'Gan, Yonghua', 'Ji, Jia', 'Li, Xiaoyu', 'Tian, Xiangjun', 'Lu, Fushuang', 'Tan, Gang', 'Yang, Ruifu', 'Liu, Bin', 'Liu, Siqi', 'Li, Songgang', 'Wang, Jun', 'Wang, Jian', 'Cao, Wuchun', 'Yu, Jun', 'Dong, Xiaoping', 'Yang, Huanming']",Genomics Proteomics Bioinformatics,,,False
957bf72775c387d7a8a356c71de7a7f271c386b6,PMC,The E Protein Is a Multifunctional Membrane Protein of SARS-CoV,http://dx.doi.org/10.1016/S1672-0229(03)01017-9,PMC5172412,15626343,CC BY-NC-ND,"The E (envelope) protein is the smallest structural protein in all coronaviruses and is the only viral structural protein in which no variation has been detected. We conducted genome sequencing and phylogenetic analyses of SARS-CoV. Based on genome sequencing, we predicted the E protein is a transmembrane (TM) protein characterized by a TM region with strong hydrophobicity and α-helix conformation. We identified a segment (NH(2)-_L-Cys-A-Y-Cys-Cys-N_-COOH) in the carboxyl-terminal region of the E protein that appears to form three disulfide bonds with another segment of corresponding cysteines in the carboxyl-terminus of the S (spike) protein. These bonds point to a possible structural association between the E and S proteins. Our phylogenetic analyses of the E protein sequences in all published coronaviruses place SARS-CoV in an independent group in Coronaviridae and suggest a non-human animal origin.",2003 May 28,"['Wu, Qingfa', 'Zhang, Yilin', 'Lü, Hong', 'Wang, Jing', 'He, Ximiao', 'Liu, Yong', 'Ye, Chen', 'Lin, Wei', 'Hu, Jianfei', 'Ji, Jia', 'Xu, Jing', 'Ye, Jia', 'Hu, Yongwu', 'Chen, Wenjun', 'Li, Songgang', 'Wang, Jun', 'Wang, Jian', 'Bi, Shengli', 'Yang, Huanming']",Genomics Proteomics Bioinformatics,,,False
49e1fb99182dcce14548cd974623d53a5ef486a7,PMC,The C-Terminal Portion of the Nucleocapsid Protein Demonstrates SARS-CoV Antigenicity,http://dx.doi.org/10.1016/S1672-0229(03)01024-6,PMC5172413,15629031,CC BY-NC-ND,"In order to develop clinical diagnostic tools for rapid detection of SARS-CoV (severe acute respiratory syndrome-associated coronavirus) and to identify candidate proteins for vaccine development, the C-terminal portion of the nucleocapsid (NC) gene was amplified using RT-PCR from the SARS-CoV genome, cloned into a yeast expression vector (pEGH), and expressed as a glutathione S-transferase (GST) and Hisx6 double-tagged fusion protein under the control of an inducible promoter. Western analysis on the purified protein confirmed the expression and purification of the NC fusion proteins from yeast. To determine its antigenicity, the fusion protein was challenged with serum samples from SARS patients and normal controls. The NC fusion protein demonstrated high antigenicity with high specificity, and therefore, it should have great potential in designing clinical diagnostic tools and provide useful information for vaccine development.",2003 Aug 28,"['Liu, Guozhen', 'Hu, Shaohui', 'Hu, Yongwu', 'Chen, Peng', 'Yin, Jianning', 'Wen, Jie', 'Wang, Jingqiang', 'Lin, Liang', 'Liu, Jinxiu', 'You, Bo', 'Yin, Ye', 'Li, Shuting', 'Wang, Hao', 'Ren, Yan', 'Ji, Jia', 'Zhao, Xiaoqian', 'Sun, Yongqiao', 'Zhang, Xiaowei', 'Fang, Jianqiu', 'Wang, Jian', 'Liu, Siqi', 'Yu, Jun', 'Zhu, Heng', 'Yang, Huanming']",Genomics Proteomics Bioinformatics,,,False
50627f92db9c17c742fb2cc95641bad921bec3ee,PMC,Molecular Advances in Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV),http://dx.doi.org/10.1016/S1672-0229(03)01031-3,PMC5172416,15629054,CC BY-NC-ND,"The sudden outbreak of severe acute respiratory syndrome (SARS) in 2002 prompted the establishment of a global scientific network subsuming most of the traditional rivalries in the competitive field of virology. Within months of the SARS outbreak, collaborative work revealed the identity of the disastrous pathogen as SARS-associated coronavirus (SARS-CoV). However, although the rapid identification of the agent represented an important breakthrough, our understanding of the deadly virus remains limited. Detailed biological knowledge is crucial for the development of effective countermeasures, diagnostic tests, vaccines and antiviral drugs against the SARS-CoV. This article reviews the present state of molecular knowledge about SARS-CoV, from the aspects of comparative genomics, molecular biology of viral genes, evolution, and epidemiology, and describes the diagnostic tests and the anti-viral drugs derived so far based on the available molecular information.",2003 Nov 28,"['Chow, Ken Yan Ching', 'Hon, Chung Chau', 'Hui, Raymond Kin Hi', 'Wong, Raymond Tsz Yeung', 'Yip, Chi Wai', 'Zeng, Fanya', 'Leung, Frederick Chi Ching']",Genomics Proteomics Bioinformatics,,,False
1235b55dccecc856c492c27e566cc10d93934b85,PMC,The Structure Analysis and Antigenicity Study of the N Protein of SARS-CoV,http://dx.doi.org/10.1016/S1672-0229(03)01018-0,PMC5172421,15626344,CC BY-NC-ND,"The Coronaviridae family is characterized by a nucleocapsid that is composed of the genome RNA molecule in combination with the nucleoprotein (N protein) within a virion. The most striking physiochemical feature of the N protein of SARS-CoV is that it is a typical basic protein with a high predicted pI and high hydrophilicity, which is consistent with its function of binding to the ribophosphate backbone of the RNA molecule. The predicted high extent of phosphorylation of the N protein on multiple candidate phosphorylation sites demonstrates that it would be related to important functions, such as RNA-binding and localization to the nucleolus of host cells. Subsequent study shows that there is an SR-rich region in the N protein and this region might be involved in the protein-protein interaction. The abundant antigenic sites predicted in the N protein, as well as experimental evidence with synthesized polypeptides, indicate that the N protein is one of the major antigens of the SARS-CoV. Compared with other viral structural proteins, the low variation rate of the N protein with regards to its size suggests its importance to the survival of the virus.",2003 May 28,"['Wang, Jingqiang', 'Ji, Jia', 'Ye, Jia', 'Zhao, Xiaoqian', 'Wen, Jie', 'Li, Wei', 'Hu, Jianfei', 'Li, Dawei', 'Sun, Min', 'Zeng, Haipan', 'Hu, Yongwu', 'Tian, Xiangjun', 'Tan, Xuehai', 'Xu, Ningzhi', 'Zeng, Changqing', 'Wang, Jian', 'Bi, Shengli', 'Yang, Huanming']",Genomics Proteomics Bioinformatics,,,False
2ab27ef3b962d32447ac0c528e7dc2da69ccd9bd,PMC,Preliminary Study on Detecting the SARS-CoV Specific Target cDNA Fragments by Multiplex PCR,http://dx.doi.org/10.1016/S1672-0229(04)02008-X,PMC5172431,15629044,CC BY-NC-ND,"The multiplex polymerase chain reaction (PCR) technique was applied to detect the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) specific target cDNA fragments in the present study. The target cDNA fragments of SARS-CoV were synthesized artificially according to the genome sequence of SARS-CoV in GenBank submitted by The Chinese University of Hong Kong, and were used as simulated positive samples. Five primers recommended by World Health Organization (WHO) were used to amplify the fragments by single PCR and multiplex PCR. Three target cDNA fragments (121, 182 and 302 bp), as well as the three different combinations of any two of these fragments, were amplified by single PCR. The combination of these three fragments was amplified by multiplex PCR. The results indicated that the multiplex PCR technique could be applied to detect the SARS-CoV specific target cDNA fragments successfully.",2004 Feb 28,"['Chen, Wenbing', 'Li, Shousong', 'Shao, Biying', 'Zheng, Teng', 'Jiang, Shuxun', 'Huang, Xiaorong', 'Cai, Kaizhen', 'Zhang, Zhideng']",Genomics Proteomics Bioinformatics,,,False
62eecf7872029dace49268e8bb10e6f2341e8f2e,PMC,Being the Pioneer of Life Sciences in China: —Introduction to Beijing Genomics Institute,http://dx.doi.org/10.1016/S1672-0229(04)02009-1,PMC5172448,,CC BY-NC-ND,,2004 Feb 28,"Zhang, Xin",Genomics Proteomics Bioinformatics,,,False
537abde4c5b849f55e62ff102f4f91dfca742ff7,PMC,SARS-CoV Genome Polymorphism: A Bioinformatics Study,http://dx.doi.org/10.1016/S1672-0229(05)03004-4,PMC5172477,16144519,CC BY-NC-ND,"A dataset of 103 SARS-CoV isolates (101 human patients and 2 palm civets) was investigated on different aspects of genome polymorphism and isolate classification. The number and the distribution of single nucleotide variations (SNVs) and insertions and deletions, with respect to a “profile”, were determined and discussed (""profile"" being a sequence containing the most represented letter per position). Distribution of substitution categories per codon positions, as well as synonymous and non-synonymous substitutions in coding regions of annotated isolates, was determined, along with amino acid (a.a.) property changes. Similar analysis was performed for the spike (S) protein in all the isolates (55 of them being predicted for the first time). The ratio Ka/Ks confirmed that the S gene was subjected to the Darwinian selection during virus transmission from animals to humans. Isolates from the dataset were classified according to genome polymorphism and genotypes. Genome polymorphism yields to two groups, one with a small number of SNVs and another with a large number of SNVs, with up to four subgroups with respect to insertions and deletions. We identified three basic nine-locus genotypes: TTTT/TTCGG, CGCC/TTCAT, and TGCC/TTCGT, with four subgenotypes. Both classifications proposed are in accordance with the new insights into possible epidemiological spread, both in space and time.",2005 Nov 28,"['Pavlović-Lažetić, Gordana M.', 'Mitić, Nenad S.', 'Tomović, Andrija M.', 'Pavlović, Mirjana D.', 'Beljanski, Miloš V.']",Genomics Proteomics Bioinformatics,,,False
835c46cb0103ede80257c6b4d5c710185f88ebf4,PMC,SARS-CoV Genome Polymorphism: A Bioinformatics Study,http://dx.doi.org/10.1016/S1672-0229(05)03004-4,PMC5172477,16144519,CC BY-NC-ND,"A dataset of 103 SARS-CoV isolates (101 human patients and 2 palm civets) was investigated on different aspects of genome polymorphism and isolate classification. The number and the distribution of single nucleotide variations (SNVs) and insertions and deletions, with respect to a “profile”, were determined and discussed (""profile"" being a sequence containing the most represented letter per position). Distribution of substitution categories per codon positions, as well as synonymous and non-synonymous substitutions in coding regions of annotated isolates, was determined, along with amino acid (a.a.) property changes. Similar analysis was performed for the spike (S) protein in all the isolates (55 of them being predicted for the first time). The ratio Ka/Ks confirmed that the S gene was subjected to the Darwinian selection during virus transmission from animals to humans. Isolates from the dataset were classified according to genome polymorphism and genotypes. Genome polymorphism yields to two groups, one with a small number of SNVs and another with a large number of SNVs, with up to four subgroups with respect to insertions and deletions. We identified three basic nine-locus genotypes: TTTT/TTCGG, CGCC/TTCAT, and TGCC/TTCGT, with four subgenotypes. Both classifications proposed are in accordance with the new insights into possible epidemiological spread, both in space and time.",2005 Nov 28,"['Pavlović-Lažetić, Gordana M.', 'Mitić, Nenad S.', 'Tomović, Andrija M.', 'Pavlović, Mirjana D.', 'Beljanski, Miloš V.']",Genomics Proteomics Bioinformatics,,,False
38cffe92191325b653dae65b1e62a10881474aa9,PMC,Systems Biology Brings Life Sciences Closer: —Report on the China-UK Systems Biology Workshop 2005,http://dx.doi.org/10.1016/S1672-0229(05)03025-1,PMC5172556,,CC BY-NC-ND,,2005 Nov 28,"Chen, Ming",Genomics Proteomics Bioinformatics,,,False
72e25d8530d2d778392e2ca2a1ec1b7e13e24a30,PMC,Toxicogenomics analysis of mouse lung responses following exposure to titanium dioxide nanomaterials reveal their disease potential at high doses,http://dx.doi.org/10.1093/mutage/gew048,PMC5180171,27760801,CC BY-NC,"Titanium dioxide nanoparticles (TiO(2)NPs) induce lung inflammation in experimental animals. In this study, we conducted a comprehensive toxicogenomic analysis of lung responses in mice exposed to six individual TiO(2)NPs exhibiting different sizes (8, 20 and 300nm), crystalline structure (anatase, rutile or anatase/rutile) and surface modifications (hydrophobic or hydrophilic) to investigate whether the mechanisms leading to TiO(2)NP-induced lung inflammation are property specific. A detailed histopathological analysis was conducted to investigate the long-term disease implications of acute exposure to TiO(2)NPs. C57BL/6 mice were exposed to 18, 54, 162 or 486 µg of TiO(2)NPs/mouse via single intratracheal instillation. Controls were exposed to dispersion medium only. Bronchoalveolar lavage fluid (BALF) and lung tissue were sampled on 1, 28 and 90 days post-exposure. Although all TiO(2)NPs induced lung inflammation as measured by the neutrophil influx in BALF, rutile-type TiO(2)NPs induced higher inflammation with the hydrophilic rutile TiO(2)NP showing the maximum increase. Accordingly, the rutile TiO(2)NPs induced higher number of differentially expressed genes. Histopathological analysis of lung sections on Day 90 post-exposure showed increased collagen staining and fibrosis-like changes following exposure to the rutile TiO(2)NPs at the highest dose tested. Among the anatase, the smallest TiO(2)NP of 8nm showed the maximum response. The anatase TiO(2)NP of 300nm was the least responsive of all. The results suggest that the severity of lung inflammation is property specific; however, the underlying mechanisms (genes and pathways perturbed) leading to inflammation were the same for all particle types. While the particle size clearly influenced the overall acute lung responses, a combination of small size, crystalline structure and hydrophilic surface contributed to the long-term pathological effects observed at the highest dose (486 µg/mouse). Although the dose at which the pathological changes were observed is considered physiologically high, the study highlights the disease potential of certain TiO(2)NPs of specific properties.",2017 Jan 19,"['Rahman, Luna', 'Wu, Dongmei', 'Johnston, Michael', 'William, Andrew', 'Halappanavar, Sabina']",Mutagenesis,,,True
dfaf551127ff5cc102d0ced7f3d9d15a5d3de8a7,PMC,China-Africa Health Development Initiatives: Benefits and Implications for Shaping Innovative and Evidence-informed National Health Policies and Programs in Sub-saharan African Countries,,PMC5187644,28058199,CC BY-NC-SA,"BACKGROUND AND INTRODUCTION: This review paper examines the growing implications of China’s engagement in shaping innovative national initiatives against infectious diseases and poverty control and elimination in African countries. It seeks to understand the factors and enhancers that can promote mutual and innovative health development initiatives, and those that are necessary in generating reliable and quality data for evidence-based contextual policy, priorities and programs. METHODS: We examined the China-Africa health cooperation in supporting global health agenda on infectious diseases such as malaria, schistosomiasis, Ebola, TB, HIV/AIDS, neglected tropical diseases (NTDs) prevention, control and elimination spanning a period of 10 years. We reviewed referenced publications, global support data, and extensive sources related to and other emerging epidemics and infectious diseases of poverty, programs and interventions, health systems development issues, challenges, opportunities and investments. Published literature in PubMed, Scopus, Google Scholar, Books and web-based peer-reviewed journal articles, government annual reports were assessed from the first Forum on China-Africa Cooperation (FOCAC) in November 2006 to December 2015 Third Ministerial conferences. RESULTS: Our findings highlight current shared public health challenges and emphasize the need to nurture, develop and establish effective, functional and sustainable health systems capacity to detect and respond to all public health threats and epidemic burdens, evidence-based programs and quality care outcomes. China’s significant health diplomacy emphasizes the importance of health financing in establishing health development commitment and investment in improving the gains and opportunities, importantly efficiency and value health priorities and planning. CONCLUSIONS AND GLOBAL HEALTH IMPLICATIONS: Strengthening China-Africa health development agenda towards collective commitment and investment in quality care delivery, effective programs coverage and efficiency, preparedness and emergency response is needed in transforming African health information systems, and local health governance structures and management in emerging epidemics. Furthermore, innovative evidence of operational joint solutions and strategies are critical in advancing healthcare delivery, and further enhancing Universal Health Care, and Sustainable Development Goals to attain global health improvements and economic prosperity.",2016,"['Tambo, Ernest', 'Ugwu, Chidiebere E.', 'Guan, Yayi', 'Wei, Ding', 'Xiao-Ning,', 'Xiao-Nong, Zhou']",Int J MCH AIDS,,,True
e32449e2444438d63a3b088859156405a461ba2e,PMC,Biological cryo‐electron microscopy in China,http://dx.doi.org/10.1002/pro.3018,PMC5192968,27534377,CC BY-NC-ND,"Cryo‐electron microscopy (cryo‐EM) plays an increasingly more important role in structural biology. With the construction of an arm of the Chinese National Protein Science Facility at Tsinghua University, biological cryo‐EM has entered a phase of rapid development in China. This article briefly reviews the history of biological cryo‐EM in China, describes its current status, comments on its impact on the various biological research fields, and presents future outlook.",2017 Jan 2,"['Wang, Hong‐Wei', 'Lei, Jianlin', 'Shi, Yigong']",Protein Sci,,,True
c745ca78351211b549476ef12e4cccf3fc3f5b84,PMC,Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses,http://dx.doi.org/10.1093/gbe/evw246,PMC5203785,27797946,CC BY-NC,"Within the last 15 years, two related coronaviruses (Severe Acute Respiratory Syndrome [SARS]-CoV and Middle East Respiratory Syndrome [MERS]-CoV) expanded their host range to include humans, with increased virulence in their new host. Coronaviruses were recently found to have little intrinsic disorder compared with many other virus families. Because intrinsically disordered regions have been proposed to be important for rewiring interactions between virus and host, we investigated the conservation of intrinsic disorder and secondary structure in coronaviruses in an evolutionary context. We found that regions of intrinsic disorder are rarely conserved among different coronavirus protein families, with the primary exception of the nucleocapsid. Also, secondary structure predictions are only conserved across 50–80% of sites for most protein families, with the implication that 20–50% of sites do not have conserved secondary structure prediction. Furthermore, nonconserved structure sites are significantly less constrained in sequence divergence than either sites conserved in the secondary structure or sites conserved in loop. Avoiding regions symptomatic of conformational flexibility such as disordered sites and sites with nonconserved secondary structure to identify potential broad-specificity antiviral targets, only one sequence motif (five residues or longer) remains from the >10,000 starting sites across all coronaviruses in this study. The identified sequence motif is found within the nonstructural protein (NSP) 12 and constitutes an antiviral target potentially effective against the present day and future coronaviruses. On shorter evolutionary timescales, the SARS and MERS clades have more sequence motifs fulfilling the criteria applied. Interestingly, many motifs map to NSP12 making this a prime target for coronavirus antivirals.",2016 Nov 9,"['Rahaman, Jordon', 'Siltberg-Liberles, Jessica']",Genome Biol Evol,,,True
56af45772bf466cc78cfdbbd2ce29543059e83e2,PMC,Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses,http://dx.doi.org/10.1093/gbe/evw246,PMC5203785,27797946,CC BY-NC,"Within the last 15 years, two related coronaviruses (Severe Acute Respiratory Syndrome [SARS]-CoV and Middle East Respiratory Syndrome [MERS]-CoV) expanded their host range to include humans, with increased virulence in their new host. Coronaviruses were recently found to have little intrinsic disorder compared with many other virus families. Because intrinsically disordered regions have been proposed to be important for rewiring interactions between virus and host, we investigated the conservation of intrinsic disorder and secondary structure in coronaviruses in an evolutionary context. We found that regions of intrinsic disorder are rarely conserved among different coronavirus protein families, with the primary exception of the nucleocapsid. Also, secondary structure predictions are only conserved across 50–80% of sites for most protein families, with the implication that 20–50% of sites do not have conserved secondary structure prediction. Furthermore, nonconserved structure sites are significantly less constrained in sequence divergence than either sites conserved in the secondary structure or sites conserved in loop. Avoiding regions symptomatic of conformational flexibility such as disordered sites and sites with nonconserved secondary structure to identify potential broad-specificity antiviral targets, only one sequence motif (five residues or longer) remains from the >10,000 starting sites across all coronaviruses in this study. The identified sequence motif is found within the nonstructural protein (NSP) 12 and constitutes an antiviral target potentially effective against the present day and future coronaviruses. On shorter evolutionary timescales, the SARS and MERS clades have more sequence motifs fulfilling the criteria applied. Interestingly, many motifs map to NSP12 making this a prime target for coronavirus antivirals.",2016 Nov 9,"['Rahaman, Jordon', 'Siltberg-Liberles, Jessica']",Genome Biol Evol,,,False
8054ef2b8d9ea141c639e476159fcdbcb18d543e,PMC,Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses,http://dx.doi.org/10.1093/gbe/evw246,PMC5203785,27797946,CC BY-NC,"Within the last 15 years, two related coronaviruses (Severe Acute Respiratory Syndrome [SARS]-CoV and Middle East Respiratory Syndrome [MERS]-CoV) expanded their host range to include humans, with increased virulence in their new host. Coronaviruses were recently found to have little intrinsic disorder compared with many other virus families. Because intrinsically disordered regions have been proposed to be important for rewiring interactions between virus and host, we investigated the conservation of intrinsic disorder and secondary structure in coronaviruses in an evolutionary context. We found that regions of intrinsic disorder are rarely conserved among different coronavirus protein families, with the primary exception of the nucleocapsid. Also, secondary structure predictions are only conserved across 50–80% of sites for most protein families, with the implication that 20–50% of sites do not have conserved secondary structure prediction. Furthermore, nonconserved structure sites are significantly less constrained in sequence divergence than either sites conserved in the secondary structure or sites conserved in loop. Avoiding regions symptomatic of conformational flexibility such as disordered sites and sites with nonconserved secondary structure to identify potential broad-specificity antiviral targets, only one sequence motif (five residues or longer) remains from the >10,000 starting sites across all coronaviruses in this study. The identified sequence motif is found within the nonstructural protein (NSP) 12 and constitutes an antiviral target potentially effective against the present day and future coronaviruses. On shorter evolutionary timescales, the SARS and MERS clades have more sequence motifs fulfilling the criteria applied. Interestingly, many motifs map to NSP12 making this a prime target for coronavirus antivirals.",2016 Nov 9,"['Rahaman, Jordon', 'Siltberg-Liberles, Jessica']",Genome Biol Evol,,,False
c4ad1eb3352c4b02e769ba152f1fa89209a0e70a,PMC,Clinical Impact of Mixed Respiratory Viral Infection in Children with Adenoviral Infection,http://dx.doi.org/10.3947/ic.2016.48.4.309,PMC5204010,27883373,CC BY-NC,"BACKGROUND: Although adenovirus (ADV) infection occurs steadily all year round in Korea and the identification of respiratory viral coinfections has been increasing following the introduction of multiplex real-time polymerase chain reaction tests, the clinical impact of viral coinfection in children with ADV infection has rarely been reported. MATERIALS AND METHODS: Medical records of children diagnosed with ADV infection were retrospectively reviewed. The enrolled children were divided into two groups based on the identified respiratory viruses: ADV group and coinfection group. Clinical and laboratory parameters were compared between the two groups. RESULTS: In total, 105 children (60 males and 45 females) with a median age of 29 months (range: 0-131 months) diagnosed with an ADV infection were enrolled. Fever (99.0%) was by far the most frequent symptom, followed by respiratory (82.9%), and gastrointestinal (22.9%) symptoms. Upper and lower respiratory tract infections were diagnosed in 56 (53.3%), and 32 (30.5%) children, respectively. Five (4.8%) children received oxygen therapy, and no child died due to ADV infection. Coinfection was diagnosed in 32 (30.5%) children, with rhinovirus (46.9%), and respiratory syncytial virus (21.9%) being the most frequent. The proportions of children younger than 24 months (P <0.001), with underlying medical conditions (P = 0.020), and diagnosed with lower respiratory tract infection (P = 0.011) were significantly higher in the coinfection group than in the ADV group. In a multivariate analysis, only the younger age was significantly associated with coinfection (P <0.001). Although more children in the coinfection group received oxygen therapy (P = 0.029), the duration of fever and hospitalization was not significantly different between the two groups. CONCLUSION: Respiratory viral coinfection with ADV occurred more frequently in children younger than 24 months of age compared with children aged 24 months or older. Respiratory viral coinfection may increase the severity of ADV infection, however, appropriate therapy prevented prolonged hospitalization and poor prognosis due to coinfection.",2016 Dec 21,"['Lee, Hyun Jun', 'Seo, Young Eun', 'Han, Seung Beom', 'Jeong, Dae Chul', 'Kang, Jin Han']",Infect Chemother,,,True
4f03e55d6a48282637116273820d4114459abfb0,PMC,Beyond the Routine Influenza Surveillance,http://dx.doi.org/10.3947/ic.2016.48.4.344,PMC5204017,28032488,CC BY-NC,,2016 Dec 21,"Choi, Sang-Ho",Infect Chemother,,,True
49a7701b214e24e40679127c598881fa579f97dd,PMC,Prevalence of Diabetes in the 2009 Influenza A (H1N1) and the Middle East Respiratory Syndrome Coronavirus: A Systematic Review and Meta-Analysis,http://dx.doi.org/10.4081/jphr.2016.733,PMC5206772,28083520,CC BY-NC,"Over the past two decades a number of severe acute respiratory infection outbreaks such as the 2009 influenza A (H1N1) and the Middle East respiratory syndrome coronavirus (MERS-CoV) have emerged and presented a considerable global public health threat. Epidemiologic evidence suggests that diabetic subjects are more susceptible to these conditions. However, the prevalence of diabetes in H1N1 and MERS-CoV has not been systematically described. The aim of this study is to conduct a systematic review and meta-analysis of published reports documenting the prevalence of diabetes in H1N1 and MERS-CoV and compare its frequency in the two viral conditions. Meta-analysis for the proportions of subjects with diabetes was carried out in 29 studies for H1N1 (n=92,948) and 9 for MERS-CoV (n=308). Average age of H1N1 patients (36.2±6.0 years) was significantly younger than that of subjects with MERS-CoV (54.3±7.4 years, P<0.05). Compared to MERS-CoV patients, subjects with H1N1 exhibited 3-fold lower frequency of cardiovascular diseases and 2- and 4-fold higher prevalence of obesity and immunosuppression, respectively. The overall prevalence of diabetes in H1N1 was 14.6% (95% CI: 12.3-17.0%; P<0.001), a 3.6-fold lower than in MERS-CoV (54.4%; 95% CI: 29.4-79.5; P<0.001). The prevalence of diabetes among H1N1 cases from Asia and North America was ~two-fold higher than those from South America and Europe. The prevalence of diabetes in MERS-CoV cases is higher than in H1N1. Regional comparisons suggest that an etiologic role of diabetes in MERS-CoV may exist distinctive from that in H1N1.",2016 Dec 21,"['Badawi, Alaa', 'Ryoo, Seung Gwan']",J Public Health Res,,,True
4db442dee5f7675795f576b1f6b7be277decf03b,PMC,Elevated thrombopoietin and platelet indices confirm active thrombopoiesis but fail to predict clinical severity of puumala hantavirus infection,http://dx.doi.org/10.1097/MD.0000000000005689,PMC5207557,28033261,CC BY-NC,"We evaluated the mechanisms of thrombocytopenia and procoagulant changes in relation with clinical variables in a cohort of patients with acute hantavirus disease. Blood samples of 33 prospectively recruited, consecutive, hospitalized patients with acute Puumala virus–induced hemorrhagic fever with renal syndrome (HFRS) were collected acutely and at the recovery visit (control). Serum thrombopoietin (TPO) and activity of plasma microparticles (MPs) from various cell sources were measured with enzyme-linked immunosorbent assay-based methods. The results were related to data on platelet indices and functions, coagulation variables, and clinical disease. Serum TPO was nearly 4-fold higher acutely compared with the control (median 207 pg/mL, range 56–1258 pg/mL vs. median 58 pg/mL, range 11–241 pg/mL, P < 0.001) and coincided with high mean platelet volume (MPV) and immature platelet fraction (IPF%). Prothrombin fragments and D-dimer were high acutely compared with the control (F1 + 2 median 704 pmol/L, range 284–1875 pmol/L vs. median 249 pmol/L, range 118–556 pmol/L, P < 0.001; d-dimer median 2.8 mg/L, range 0.6–34.0 mg/L vs. median 0.4 mg/L, range 0.2–1.1 mg/L, P < 0.001), and associated with low platelet count and severe acute kidney injury (AKI). MPs’ procoagulant activity was high acutely only among patients with mild AKI (plasma creatinine below the median at the time of the measurement). Upregulated TPO together with high MPV and IPF% confirm active thrombopoiesis, but do not predict severity of HFRS. Simultaneously, elevated prothrombin fragments and d-dimer suggest increased consumption of platelets in patients with severe AKI. Activity of platelet-derived MPs in HFRS should be studied with flow cytometry in a larger cohort of patients.",2016 Dec 30,"['Laine, Outi', 'Joutsi-Korhonen, Lotta', 'Lassila, Riitta', 'Huhtala, Heini', 'Vaheri, Antti', 'Mäkelä, Satu', 'Mustonen, Jukka']",Medicine (Baltimore),,,True
1c3abd60f3deefb350c36d0f51ba2ae27eff56b5,PMC,IMG/VR: a database of cultured and uncultured DNA Viruses and retroviruses,http://dx.doi.org/10.1093/nar/gkw1030,PMC5210529,27799466,CC BY-NC,"Viruses represent the most abundant life forms on the planet. Recent experimental and computational improvements have led to a dramatic increase in the number of viral genome sequences identified primarily from metagenomic samples. As a result of the expanding catalog of metagenomic viral sequences, there exists a need for a comprehensive computational platform integrating all these sequences with associated metadata and analytical tools. Here we present IMG/VR (https://img.jgi.doe.gov/vr/), the largest publicly available database of 3908 isolate reference DNA viruses with 264 413 computationally identified viral contigs from >6000 ecologically diverse metagenomic samples. Approximately half of the viral contigs are grouped into genetically distinct quasi-species clusters. Microbial hosts are predicted for 20 000 viral sequences, revealing nine microbial phyla previously unreported to be infected by viruses. Viral sequences can be queried using a variety of associated metadata, including habitat type and geographic location of the samples, or taxonomic classification according to hallmark viral genes. IMG/VR has a user-friendly interface that allows users to interrogate all integrated data and interact by comparing with external sequences, thus serving as an essential resource in the viral genomics community.",2017 Jan 4,"['Paez-Espino, David', 'Chen, I.-Min A.', 'Palaniappan, Krishna', 'Ratner, Anna', 'Chu, Ken', 'Szeto, Ernest', 'Pillay, Manoj', 'Huang, Jinghua', 'Markowitz, Victor M.', 'Nielsen, Torben', 'Huntemann, Marcel', 'K.\xa0Reddy, T. B.', 'Pavlopoulos, Georgios A.', 'Sullivan, Matthew B.', 'Campbell, Barbara J.', 'Chen, Feng', 'McMahon, Katherine', 'Hallam, Steve J.', 'Denef, Vincent', 'Cavicchioli, Ricardo', 'Caffrey, Sean M.', 'Streit, Wolfgang R.', 'Webster, John', 'Handley, Kim M.', 'Salekdeh, Ghasem H.', 'Tsesmetzis, Nicolas', 'Setubal, Joao C.', 'Pope, Phillip B.', 'Liu, Wen-Tso', 'Rivers, Adam R.', 'Ivanova, Natalia N.', 'Kyrpides, Nikos C.']",Nucleic Acids Res,,,True
fca7adbc5fdaeba0fedd1201e496704b1a888556,PMC,MRPrimerV: a database of PCR primers for RNA virus detection,http://dx.doi.org/10.1093/nar/gkw1095,PMC5210568,27899620,CC BY-NC,"Many infectious diseases are caused by viral infections, and in particular by RNA viruses such as MERS, Ebola and Zika. To understand viral disease, detection and identification of these viruses are essential. Although PCR is widely used for rapid virus identification due to its low cost and high sensitivity and specificity, very few online database resources have compiled PCR primers for RNA viruses. To effectively detect viruses, the MRPrimerV database (http://MRPrimerV.com) contains 152 380 247 PCR primer pairs for detection of 1818 viruses, covering 7144 coding sequences (CDSs), representing 100% of the RNA viruses in the most up-to-date NCBI RefSeq database. Due to rigorous similarity testing against all human and viral sequences, every primer in MRPrimerV is highly target-specific. Because MRPrimerV ranks CDSs by the penalty scores of their best primer, users need only use the first primer pair for a single-phase PCR or the first two primer pairs for two-phase PCR. Moreover, MRPrimerV provides the list of genome neighbors that can be detected using each primer pair, covering 22 192 variants of 532 RefSeq RNA viruses. We believe that the public availability of MRPrimerV will facilitate viral metagenomics studies aimed at evaluating the variability of viruses, as well as other scientific tasks.",2017 Jan 4,"['Kim, Hyerin', 'Kang, NaNa', 'An, KyuHyeon', 'Kim, Doyun', 'Koo, JaeHyung', 'Kim, Min-Soo']",Nucleic Acids Res,,,True
94c1ee6fefd3a09fdf245d6d4a0c2321c9d994de,PMC,EuPathDB: the eukaryotic pathogen genomics database resource,http://dx.doi.org/10.1093/nar/gkw1105,PMC5210576,27903906,CC BY-NC,"The Eukaryotic Pathogen Genomics Database Resource (EuPathDB, http://eupathdb.org) is a collection of databases covering 170+ eukaryotic pathogens (protists & fungi), along with relevant free-living and non-pathogenic species, and select pathogen hosts. To facilitate the discovery of meaningful biological relationships, the databases couple preconfigured searches with visualization and analysis tools for comprehensive data mining via intuitive graphical interfaces and APIs. All data are analyzed with the same workflows, including creation of gene orthology profiles, so data are easily compared across data sets, data types and organisms. EuPathDB is updated with numerous new analysis tools, features, data sets and data types. New tools include GO, metabolic pathway and word enrichment analyses plus an online workspace for analysis of personal, non-public, large-scale data. Expanded data content is mostly genomic and functional genomic data while new data types include protein microarray, metabolic pathways, compounds, quantitative proteomics, copy number variation, and polysomal transcriptomics. New features include consistent categorization of searches, data sets and genome browser tracks; redesigned gene pages; effective integration of alternative transcripts; and a EuPathDB Galaxy instance for private analyses of a user's data. Forthcoming upgrades include user workspaces for private integration of data with existing EuPathDB data and improved integration and presentation of host–pathogen interactions.",2017 Jan 4,"['Aurrecoechea, Cristina', 'Barreto, Ana', 'Basenko, Evelina Y.', 'Brestelli, John', 'Brunk, Brian P.', 'Cade, Shon', 'Crouch, Kathryn', 'Doherty, Ryan', 'Falke, Dave', 'Fischer, Steve', 'Gajria, Bindu', 'Harb, Omar S.', 'Heiges, Mark', 'Hertz-Fowler, Christiane', 'Hu, Sufen', 'Iodice, John', 'Kissinger, Jessica C.', 'Lawrence, Cris', 'Li, Wei', 'Pinney, Deborah F.', 'Pulman, Jane A.', 'Roos, David S.', 'Shanmugasundram, Achchuthan', 'Silva-Franco, Fatima', 'Steinbiss, Sascha', 'Stoeckert, Christian J.', 'Spruill, Drew', 'Wang, Haiming', 'Warrenfeltz, Susanne', 'Zheng, Jie']",Nucleic Acids Res,,,True
746804f73409212ee4161597d1ebb4fd5e8cd296,PMC,Viral evasion of DNA-stimulated innate immune responses,http://dx.doi.org/10.1038/cmi.2016.06,PMC5214947,26972769,CC BY-NC-SA,"Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP–AMP synthase (cGAS) and gamma-interferon-inducible protein (IFI16), has led to understanding of how cells evoke strong innate immune responses against incoming pathogens carrying DNA genomes. The signaling stimulated by DNA sensors depends on the adaptor protein STING (stimulator of interferon genes), to enable expression of antiviral proteins, including type I interferon. To facilitate efficient infections, viruses have evolved a wide range of evasion strategies, targeting host DNA sensors, adaptor proteins and transcription factors. In this review, the current literature on virus-induced activation of the STING pathway is presented and we discuss recently identified viral evasion mechanisms targeting different steps in this antiviral pathway.",2017 Jan 14,"['Christensen, Maria H', 'Paludan, Søren R']",Cell Mol Immunol,,,True
d25e73fba5d8ef3d694dcc923c5f7776efa46954,PMC,A Pneumonia Case Associated with Type 2 Polio Vaccine Strains,http://dx.doi.org/10.4103/0366-6999.196575,PMC5221101,28051034,CC BY-NC-SA,,2017 Jan 5,"['Li, Mao-Zhong', 'Zhang, Tie-Gang', 'Li, Ai-Hua', 'Luo, Ming', 'Jiao, Yang', 'Dong, Mei', 'Gong, Cheng', 'Huang, Fang']",Chin Med J (Engl),,,True
845be0716daab542bf27a9d735e03f86a8f3ea85,PMC,High-throughput Detection of Respiratory Pathogens in Animal Specimens by Nanoscale PCR,http://dx.doi.org/10.3791/54781,PMC5226323,27929456,CC BY-NC-ND,"Nanoliter scale real-time PCR uses spatial multiplexing to allow multiple assays to be run in parallel on a single plate without the typical drawbacks of combining reactions together. We designed and evaluated a panel based on this principle to rapidly identify the presence of common disease agents in dogs and horses with acute respiratory illness. This manuscript describes a nanoscale diagnostic PCR workflow for sample preparation, amplification, and analysis of target pathogen sequences, focusing on procedures that are different from microliter scale reactions. In the respiratory panel presented, 18 assays were each set up in triplicate, accommodating up to 48 samples per plate. A universal extraction and pre-amplification workflow was optimized for high-throughput sample preparation to accommodate multiple matrices and DNA and RNA based pathogens. Representative data are presented for one RNA target (influenza A matrix) and one DNA target (equine herpesvirus 1). The ability to quickly and accurately test for a comprehensive, syndrome-based group of pathogens is a valuable tool for improving efficiency and ergonomics of diagnostic testing and for acute respiratory disease diagnosis and management.",2016 Nov 28,"['Goodman, Laura B.', 'Anderson, Renee R.', 'Slater, Marcia', 'Ortenberg, Elen', 'Renshaw, Randall W.', 'Chilson, Brittany D.', 'Laverack, Melissa A.', 'Beeby, John S.', 'Dubovi, Edward J.', 'Glaser, Amy L.']",J Vis Exp,,,True
24d4cd7729a8df22c9cab12f20e96aa9bf1332a2,PMC,The Relationships between Respiratory Virus Infection and Aminotransferase in Children,http://dx.doi.org/10.5223/pghn.2016.19.4.243,PMC5234413,28090469,CC BY-NC,"PURPOSE: We sought to examine the relationship between the clinical manifestations of nonspecific reactive hepatitis and respiratory virus infection in pediatric patients. METHODS: Patients admitted to the pediatric unit of Konyang University Hospital for lower respiratory tract disease between January 1, 2014 and December 31, 2014 and who underwent reverse transcriptase polymerase chain reaction tests were examined. The patients were divided into those with increased levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and those with normal ALT or AST levels. Further, patients with increased ALT and AST levels were individually compared with patients in the normal group, and the blood test results were compared according to the type of respiratory virus. RESULTS: Patients with increased ALT or AST levels had one more day of hospital stay, on average, compared with patients in the normal group (5.3±3.1 days vs. 4.4±3.0 days, p=0.019). Patients in the increased ALT level group were younger and had a longer mean hospital stay, compared with patients in the normal group (p=0.022 and 0.003, respectively). The incidences of increased ALT or AST were the highest in adenovirus infections (6/24, 25.0%), followed by enterovirus (2/11, 18.2%) and respiratory syncytial virus A (21/131, 16.0%) infections. CONCLUSION: Nonspecific reactive hepatitis is more common among patients with adenovirus, enterovirus and respiratory syncytial virus infection, as well as among those infected at a younger age. Compared with AST levels, ALT levels are better indicators of the severity of nonspecific reactive hepatitis.",2016 Dec 28,"['Oh, Jun Suk', 'Choi, Jun Sik', 'Lee, Young Hyuk', 'Ko, Kyung Og', 'Lim, Jae Woo', 'Cheon, Eun Jung', 'Lee, Gyung Min', 'Yoon, Jung Min']",Pediatr Gastroenterol Hepatol Nutr,,,True
ef6dbb94ddc618e006e993f32893043b9fa87463,PMC,Development and application of multiplex PCR assays for detection of virus-induced respiratory disease complex in dogs,http://dx.doi.org/10.1292/jvms.16-0342,PMC5240764,27628592,CC BY-NC-ND,"Canine infectious respiratory disease complex (CIRDC) viruses have been detected in dogs with respiratory illness. Canine influenza virus (CIV), canine parainfluenza virus (CPIV), canine distemper virus (CDV), canine respiratory coronavirus (CRCoV), canine adenovirus type 2 (CAdV-2) and canine herpesvirus 1 (CaHV-1), are all associated with the CIRDC. To allow diagnosis, two conventional multiplex polymerase chain reactions (PCR) were developed to simultaneously identify four RNA and two DNA viruses associated with CIRDC. The two multiplex PCR assays were then validated on 102 respiratory samples collected from 51 dogs with respiratory illness by sensitivity and specificity determination in comparison to conventional simplex PCR and a rapid three-antigen test kit. All six viruses were detected in either individual or multiple infections. The developed multiplex PCR assays had a >87% sensitivity and 100% specificity compared to their simplex counterpart. Compared to the three-antigen test kit, the multiplex PCR assays yielded 100% sensitivity and more than 83% specificity for detection of CAdV-2 and CDV, but not for CIV. Therefore, the developed multiplex PCR modalities were able to simultaneously diagnose a panel of CIRDC viruses and facilitated specimen collection through being suitable for use of nasal or oral samples.",2016 Dec 15,"['PIEWBANG, Chutchai', 'RUNGSIPIPAT, Anudep', 'POOVORAWAN, Yong', 'TECHANGAMSUWAN, Somporn']",J Vet Med Sci,,,True
d84ced2c3a06936bb56ee529a5bdca5f6adaf857,PMC,Levodopa attenuates cellular apoptosis in steroid-associated necrosis of the femoral head,http://dx.doi.org/10.3892/etm.2016.3964,PMC5245153,28123470,CC BY-NC-ND,"The present study aimed to investigate the effects of levodopa (LEV) on cellular apoptosis in a rabbit model of steroid-associated necrosis of the femoral head (SANFH). A total of 44 healthy adult Chinese rabbits were randomly divided into three groups: Group A (n=15), administered a combination of lipopolysaccharide and hormone to establish the SANFH animal model; group B (n=15), SANFH animal model as in group A orally administered LEV (0.4 g/kg/day) on the day of injection; and group C (n=14), the control group. On the 6th and 8th week of modeling, seven rabbits from each group were sacrificed to harvest bilateral femoral head specimens for hematoxylin and eosin staining and apoptosis detection by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay analysis, as well as for observing pathological changes and analyzing cellular apoptosis. Eight weeks after modeling, the serum insulin-like growth factor (IGF)-1 levels of the three groups were measured. The empty lacunae rate and apoptosis index of bone cells in the treatment group were significantly lower than that of the model group (P<0.01). Eight weeks after treatment, the serum levels of IGF-1 were significantly higher than that of the model group (P<0.01). These findings suggested that LEV was able to reduce steroid-induced bone cellular apoptosis, reduce the occurrence of necrosis of the femoral head and, through in vivo metabolism, it may promote the synthesis and release of IGF-1, which could be one of its biological pathways to prevent and treat SANFH.",2017 Jan 7,"['Xi, Hongbo', 'Tao, Weijian', 'Jian, Zhengguang', 'Sun, Xuefeng', 'Gong, Xiaohong', 'Huang, Lixin', 'Dong, Tianhua']",Exp Ther Med,,,True
70785546b2ab863782992d42183b0df0a1916ddb,PMC,Case characteristics among Middle East respiratory syndrome coronavirus outbreak and non-outbreak cases in Saudi Arabia from 2012 to 2015,http://dx.doi.org/10.1136/bmjopen-2016-011865,PMC5253590,28082362,CC BY-NC,"OBJECTIVES: As of 1 November 2015, the Saudi Ministry of Health had reported 1273 cases of Middle East respiratory syndrome (MERS); among these cases, which included 9 outbreaks at several hospitals, 717 (56%) patients recovered, 14 (1%) remain hospitalised and 543 (43%) died. This study aimed to determine the epidemiological, demographic and clinical characteristics that distinguished cases of MERS contracted during outbreaks from those contracted sporadically (ie, non-outbreak) between 2012 and 2015 in Saudi Arabia. DESIGN: Data from the Saudi Ministry of Health of confirmed outbreak and non-outbreak cases of MERS coronavirus (CoV) infections from September 2012 through October 2015 were abstracted and analysed. Univariate and descriptive statistical analyses were conducted, and the time between disease onset and confirmation, onset and notification and onset and death were examined. RESULTS: A total of 1250 patients (aged 0–109 years; mean, 50.825 years) were reported infected with MERS-CoV. Approximately two-thirds of all MERS cases were diagnosed in men for outbreak and non-outbreak cases. Healthcare workers comprised 22% of all MERS cases for outbreak and non-outbreak cases. Nosocomial infections comprised one-third of all Saudi MERS cases; however, nosocomial infections occurred more frequently in outbreak than non-outbreak cases (p<0.001). Patients contracting MERS during an outbreak were significantly more likely to die of MERS (p<0.001). CONCLUSIONS: To date, nosocomial infections have fuelled MERS outbreaks. Given that the Kingdom of Saudi Arabia is a worldwide religious travel destination, localised outbreaks may have massive global implications and effective outbreak preventive measures are needed.",2017 Jan 12,"['Alhamlan, F S', 'Majumder, M S', 'Brownstein, J S', 'Hawkins, J', 'Al-Abdely, H M', 'Alzahrani, A', 'Obaid, D A', 'Al-Ahdal, M N', 'BinSaeed, A']",BMJ Open,,,True
88caf57eea5c40d11ffc622d97b7c057856b8625,PMC,Case characteristics among Middle East respiratory syndrome coronavirus outbreak and non-outbreak cases in Saudi Arabia from 2012 to 2015,http://dx.doi.org/10.1136/bmjopen-2016-011865,PMC5253590,28082362,CC BY-NC,"OBJECTIVES: As of 1 November 2015, the Saudi Ministry of Health had reported 1273 cases of Middle East respiratory syndrome (MERS); among these cases, which included 9 outbreaks at several hospitals, 717 (56%) patients recovered, 14 (1%) remain hospitalised and 543 (43%) died. This study aimed to determine the epidemiological, demographic and clinical characteristics that distinguished cases of MERS contracted during outbreaks from those contracted sporadically (ie, non-outbreak) between 2012 and 2015 in Saudi Arabia. DESIGN: Data from the Saudi Ministry of Health of confirmed outbreak and non-outbreak cases of MERS coronavirus (CoV) infections from September 2012 through October 2015 were abstracted and analysed. Univariate and descriptive statistical analyses were conducted, and the time between disease onset and confirmation, onset and notification and onset and death were examined. RESULTS: A total of 1250 patients (aged 0–109 years; mean, 50.825 years) were reported infected with MERS-CoV. Approximately two-thirds of all MERS cases were diagnosed in men for outbreak and non-outbreak cases. Healthcare workers comprised 22% of all MERS cases for outbreak and non-outbreak cases. Nosocomial infections comprised one-third of all Saudi MERS cases; however, nosocomial infections occurred more frequently in outbreak than non-outbreak cases (p<0.001). Patients contracting MERS during an outbreak were significantly more likely to die of MERS (p<0.001). CONCLUSIONS: To date, nosocomial infections have fuelled MERS outbreaks. Given that the Kingdom of Saudi Arabia is a worldwide religious travel destination, localised outbreaks may have massive global implications and effective outbreak preventive measures are needed.",2017 Jan 12,"['Alhamlan, F S', 'Majumder, M S', 'Brownstein, J S', 'Hawkins, J', 'Al-Abdely, H M', 'Alzahrani, A', 'Obaid, D A', 'Al-Ahdal, M N', 'BinSaeed, A']",BMJ Open,,,False
7db9b801730d8b60d1fc331ba3389460e9ea3794,PMC,Effects of 3-Dimensional Lumbar Stabilization Training for Balance in Chronic Hemiplegic Stroke Patients: A Randomized Controlled Trial,http://dx.doi.org/10.5535/arm.2016.40.6.972,PMC5256321,28119826,CC BY-NC,"OBJECTIVE: To investigate the effects of the newly developed Spine Balance 3D system on the balance and gait abilities of hemiplegic stroke patients. METHODS: Twenty-eight hemiplegic patients with chronic stroke were randomly assigned to an experimental (n=14) or control group (n=14). The experimental and control groups performed balance training by using the newly developed Spine Balance 3D system and the well-known Biodex Balance System 30 minutes per day, three times a week for 7 weeks. The Berg Balance Scale (BBS), 10-m walking test (10mWT), Timed Up and Go Test (TUG), Functional Reach Test (FRT), the Korean version of the Fall Efficacy Scale-International (KFES-I), trunk muscle strength and stability were evaluated before and after 7 weeks of intervention. RESULTS: The 10mWT improved significantly (p=0.001) in the experimental group (using the Spine Balance 3D system) but not in the control group, and core muscle strength, which we checked using Spine Balance 3D system evaluation program, improved more in the experimental group as well. The results of the BBS, FRT, TUG, KFES-I, and Biodex Balance System evaluation program improved in both groups after 7 weeks of balance training. CONCLUSION: We suggest that the newly-developed Spine Balance 3D system can be a more useful therapeutic tool for gait and dynamic balance rehabilitation in hemiplegic patients than a conventional 2D-based balance training system. A large-scale randomized controlled study is needed to prove the effect of this system.",2016 Dec 30,"['Chun, Jin-Young', 'Seo, Jeong-Hwan', 'Park, Sung-Hee', 'Won, Yu Hui', 'Kim, Gi-Wook', 'Moon, Sung-Jun', 'Ko, Myoung-Hwan']",Ann Rehabil Med,,,True
52069d14f038d493dce5d6cc1fdcdc7c1f0823f9,PMC,Research Communications of the 26(th) ECVIM‐CA CONGRESS,http://dx.doi.org/10.1111/jvim.14600,PMC5259643,,CC BY-NC,,2017 Jan 2 Jan-Feb,,J Vet Intern Med,,,True
760fa9225c5f571c77674f53a1f2d9648eb2adb0,PMC,The Utility of Acute‐Phase Proteins in the Assessment of Treatment Response in Dogs With Bacterial Pneumonia,http://dx.doi.org/10.1111/jvim.14631,PMC5259651,28032360,CC BY-NC,"BACKGROUND: Acute‐phase proteins (APPs) are sensitive markers of inflammation, and serum C‐reactive protein (CRP) recently has been shown to be a useful diagnostic marker in dogs with bacterial pneumonia (BP). In humans with community‐acquired pneumonia, APPs also have great utility as follow‐up markers aiding in the assessment of treatment response. OBJECTIVES: The aim of our study was to investigate the applicability of APPs as markers of treatment response in dogs with BP. ANIMALS: Nineteen dogs diagnosed with BP and 64 healthy dogs. METHODS: The study was conducted as a prospective longitudinal observational study. Serum CRP, serum amyloid A (SAA), and haptoglobin concentrations were followed during a natural course of BP. Normalization of serum CRP was used to guide the duration of antibiotic treatment (treatment was stopped 5–7 days after CRP normalized) in 8 of 17 dogs surviving to discharge; 9 of 17 dogs were treated according to conventional recommendations. RESULTS: All measured APPs initially were significantly increased, but the magnitude of increase was not correlated to disease severity. C‐reactive protein and SAA concentrations decreased rapidly after initiation of antimicrobial treatment. When normalization of serum CRP was used to guide the duration of antibiotic treatment, treatment duration was significantly (P = .015) decreased without increasing the number of relapses. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum CRP and SAA reflected the recovery process well and therefore may be used as markers of treatment response. According to the results, the normalization of serum CRP may be used to guide the duration of antibiotic treatment in dogs with BP.",2017 Dec 29 Jan-Feb,"['Viitanen, S.J.', 'Lappalainen, A.K.', 'Christensen, M.B.', 'Sankari, S.', 'Rajamäki, M.M.']",J Vet Intern Med,,,True
6c5eefe46e0d278ccfc29c476c8adaa18444c69c,PMC,The Utility of Acute‐Phase Proteins in the Assessment of Treatment Response in Dogs With Bacterial Pneumonia,http://dx.doi.org/10.1111/jvim.14631,PMC5259651,28032360,CC BY-NC,"BACKGROUND: Acute‐phase proteins (APPs) are sensitive markers of inflammation, and serum C‐reactive protein (CRP) recently has been shown to be a useful diagnostic marker in dogs with bacterial pneumonia (BP). In humans with community‐acquired pneumonia, APPs also have great utility as follow‐up markers aiding in the assessment of treatment response. OBJECTIVES: The aim of our study was to investigate the applicability of APPs as markers of treatment response in dogs with BP. ANIMALS: Nineteen dogs diagnosed with BP and 64 healthy dogs. METHODS: The study was conducted as a prospective longitudinal observational study. Serum CRP, serum amyloid A (SAA), and haptoglobin concentrations were followed during a natural course of BP. Normalization of serum CRP was used to guide the duration of antibiotic treatment (treatment was stopped 5–7 days after CRP normalized) in 8 of 17 dogs surviving to discharge; 9 of 17 dogs were treated according to conventional recommendations. RESULTS: All measured APPs initially were significantly increased, but the magnitude of increase was not correlated to disease severity. C‐reactive protein and SAA concentrations decreased rapidly after initiation of antimicrobial treatment. When normalization of serum CRP was used to guide the duration of antibiotic treatment, treatment duration was significantly (P = .015) decreased without increasing the number of relapses. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum CRP and SAA reflected the recovery process well and therefore may be used as markers of treatment response. According to the results, the normalization of serum CRP may be used to guide the duration of antibiotic treatment in dogs with BP.",2017 Dec 29 Jan-Feb,"['Viitanen, S.J.', 'Lappalainen, A.K.', 'Christensen, M.B.', 'Sankari, S.', 'Rajamäki, M.M.']",J Vet Intern Med,,,False
3acf7c53f21c4657d7ed19982aad3922eb6b5587,PMC,The Utility of Acute‐Phase Proteins in the Assessment of Treatment Response in Dogs With Bacterial Pneumonia,http://dx.doi.org/10.1111/jvim.14631,PMC5259651,28032360,CC BY-NC,"BACKGROUND: Acute‐phase proteins (APPs) are sensitive markers of inflammation, and serum C‐reactive protein (CRP) recently has been shown to be a useful diagnostic marker in dogs with bacterial pneumonia (BP). In humans with community‐acquired pneumonia, APPs also have great utility as follow‐up markers aiding in the assessment of treatment response. OBJECTIVES: The aim of our study was to investigate the applicability of APPs as markers of treatment response in dogs with BP. ANIMALS: Nineteen dogs diagnosed with BP and 64 healthy dogs. METHODS: The study was conducted as a prospective longitudinal observational study. Serum CRP, serum amyloid A (SAA), and haptoglobin concentrations were followed during a natural course of BP. Normalization of serum CRP was used to guide the duration of antibiotic treatment (treatment was stopped 5–7 days after CRP normalized) in 8 of 17 dogs surviving to discharge; 9 of 17 dogs were treated according to conventional recommendations. RESULTS: All measured APPs initially were significantly increased, but the magnitude of increase was not correlated to disease severity. C‐reactive protein and SAA concentrations decreased rapidly after initiation of antimicrobial treatment. When normalization of serum CRP was used to guide the duration of antibiotic treatment, treatment duration was significantly (P = .015) decreased without increasing the number of relapses. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum CRP and SAA reflected the recovery process well and therefore may be used as markers of treatment response. According to the results, the normalization of serum CRP may be used to guide the duration of antibiotic treatment in dogs with BP.",2017 Dec 29 Jan-Feb,"['Viitanen, S.J.', 'Lappalainen, A.K.', 'Christensen, M.B.', 'Sankari, S.', 'Rajamäki, M.M.']",J Vet Intern Med,,,False
6e99aa3d7287b2e04d3c2a975ba94212158ac45c,PMC,2016 ACVIM Forum Research Abstract Program,http://dx.doi.org/10.1111/jvim.13952,PMC5260423,,CC BY-NC,,2016 May 31 Jul-Aug,,J Vet Intern Med,,,True
ece140f2d510d370f594707b718066f7173a39e1,PMC,Preventative Vaccines for Zika Virus Outbreak: Preliminary Evaluation,http://dx.doi.org/10.1016/j.ebiom.2016.09.028,PMC5264651,27717627,CC BY-NC-ND,"Since it emerged in Brazil in May 2015, the mosquito-borne Zika virus (ZIKV) has raised global concern due to its association with a significant rise in the number of infants born with microcephaly and neurological disorders such as Guillain-Barré syndrome. We developed prototype subunit and adenoviral-based Zika vaccines encoding the extracellular portion of the ZIKV envelope gene (E) fused to the T4 fibritin foldon trimerization domain (Efl). The subunit vaccine was delivered intradermally through carboxymethyl cellulose microneedle array (MNA). The immunogenicity of these two vaccines, named Ad5.ZIKV-Efl and ZIKV-rEfl, was tested in C57BL/6 mice. Prime/boost immunization regimen was associated with induction of a ZIKV-specific antibody response, which provided neutralizing immunity. Moreover, protection was evaluated in seven-day-old pups after virulent ZIKV intraperitoneal challenge. Pups born to mice immunized with Ad5.ZIKV-Efl were all protected against lethal challenge infection without weight loss or neurological signs, while pups born to dams immunized with MNA-ZIKV-rEfl were partially protected (50%). No protection was seen in pups born to phosphate buffered saline-immunized mice. This study illustrates the preliminary efficacy of the E ZIKV antigen vaccination in controlling ZIKV infectivity, providing a promising candidate vaccine and antigen format for the prevention of Zika virus disease.",2016 Oct 3,"['Kim, Eun', 'Erdos, Geza', 'Huang, Shaohua', 'Kenniston, Thomas', 'Falo, Louis D.', 'Gambotto, Andrea']",EBioMedicine,,,False
bb59a75042a0be5861524532178e8becd8cda233,PMC,Extracorporeal shockwave therapy in osteonecrosis of femoral head: A systematic review of now available clinical evidences,http://dx.doi.org/10.1097/MD.0000000000005897,PMC5287958,28121934,CC BY-ND,"BACKGROUND: Osteonecrosis is an incapacitating disorder with high morbidity. Though extracorporeal shockwave therapy (ESWT) provides a noninvasive treatment option, controversial subjects still exist about its effectiveness, indications, and mechanism of action. METHODS: An electronic databases search was performed using PubMed, Embase, and the Cochrane library to collect clinical trials, case reports, and cases series on this topic and then useful data were extracted and appraised by experienced clinicians. We evaluated the quality of included evidences by using the Oxford Centre for evidence-based medicine (EBM) Levels of Evidence. RESULTS: A total of 17 articles including 2 case reports, 9 open label trials, 2 cohorts, and 6 randomized controlled trials were considered to be eligible for this systematic review. Visual analog scale (VAS), Harris hip scores, and the imaging results were the frequently-used outcome estimates of included studies. CONCLUSION: By systematically analyzing these evidences, we could conclude that ESWT could act as a safe and effective method to improve the motor function and relieve the pain of patients with osteonecrosis of femoral hip, especially those at early stage. Imaging revealed that bone marrow edema was significantly relieved, but the necrotic bone could not be reversed after ESWT. This technique could slow or even block the progression of ONFH and therefore reduce the demand for surgery. Collaboration with other conservative modalities would not improve the curative benefits of ESWT. Meanwhile, ONFH with various risk factors showed similar reaction to this noninvasive treatment method. However, these conclusions should be interpreted carefully for the low-quality of included publications and further studies are requisite to validate the effect of ESWT in ONFH.",2017 Jan 27,"['Zhang, Qingyu', 'Liu, Lihua', 'Sun, Wei', 'Gao, Fuqiang', 'Cheng, Liming', 'Li, Zirong']",Medicine (Baltimore),,,True
91abd69ad1b79240b58ffdfbce651e6980dca5bf,PMC,Preparation of a cell line persistently infected with maedi/visna virus and production of viral antigens,http://dx.doi.org/10.1292/jvms.16-0340,PMC5289251,27795464,CC BY-NC-ND,"We attempted to prepare a cell line that produces maedi/visna virus (MVV) and is free of contamination by other viruses and mycoplasmas. Three cell lines, which originated from a sheep, goat and bat, were infected with MVV and passaged approximately every 5 days. The cultured cells were then subjected to polymerase chain reaction analysis for MVV provirus. As a result, a cell line persistently infected with MVV was established from ZZ-R cells, which originated from the fetal goat tongue. The 50-fold concentrated culture fluid formed a precipitation line against reference antiserum.",2017 Jan 30,"['SUZUKI, Kazuya', 'OGUMA, Keisuke', 'SENTSUI, Hiroshi']",J Vet Med Sci,,,True
9369b15083026f2929d6eb01a67999d1800e2ec0,PMC,Reliability of clinical diagnosis and laboratory testing techniques currently used for identification of canine parvovirus enteritis in clinical settings,http://dx.doi.org/10.1292/jvms.16-0227,PMC5289263,27818461,CC BY-NC-ND,"Canine parvovirus type 2 (CPV-2) is the main etiological agent of viral enteritis in dogs. Actually in literature, CPV-2 has been reported with clinical signs that vary from the classical disease, and immunochromatography test and PCR technique have been introduced to veterinary hospitals to confirm CPV-2 diagnosis and other infections. However, the reliability of these techniques has been poorly analyzed. In this study, we evaluated the sensitivity and specificity of veterinary clinical diagnosis, immunochromatography test and PCR technique. Our data indicate that variations in the clinical signs of CPV-2 complicate the gathering of an appropriate diagnosis; and immunochromatography test and PCR technique do not have adequate sensitivity to diagnose positive cases.",2017 Jan 6,"['FAZ, Mirna', 'MARTÍNEZ, José Simón', 'QUIJANO-HERNÁNDEZ, Israel', 'FAJARDO, Raúl']",J Vet Med Sci,,,True
dcf0fae6dc17737b792734169c7d16468ab7a9dc,PMC,Lower Respiratory Tract Diseases Caused by Common Respiratory Viruses among Stem Cell Transplantation Recipients: A Single Center Experience in Korea,http://dx.doi.org/10.3349/ymj.2017.58.2.362,PMC5290016,28120567,CC BY-NC,"PURPOSE: To describe the incidence, clinical courses, and risk factors for mortality of lower respiratory tract diseases (LRDs) caused by common respiratory viruses (CRVs) in stem cell transplantation (SCT) recipients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 1038 patients who received SCT between January 2007 and August 2011 at a single center in Korea. RESULTS: Seventy-one CRV-LRDs were identified in 67 (6.5%) patients. The human parainfluenza virus (HPIV) was the most common causative pathogen of CRV-LRDs at 100 days [cumulative incidence estimate, 23.5%; 95% confidence interval (CI), 3.3–43.7] and 1 year (cumulative incidence estimate, 69.2%; 95% CI, 45.9–92.5) following SCT. The 30-day overall mortality rates due to influenza-LRDs, respiratory syncytial virus-LRDs, HPIV-LRDs, and human rhinovirus-LRDs were 35.7, 25.8, 31.6, and 42.8%, respectively. Co-pathogens in respiratory specimens were detected in 23 (33.8%) patients. The overall mortality at day 30 after CRV-LRD diagnosis was 32.8% (22/67). High-dose steroid usage (p=0.025), a severe state of immunodeficiency (p=0.033), and lymphopenia (p=0.006) were significantly associated with death within 30 days following CRV-LRD diagnosis in a univariate analysis. Multivariate logistic regression analysis revealed that high-dose steroid usage [odds ratio (OR), 4.05; 95% CI, 1.12–14.61; p=0.033] and lymphopenia (OR, 6.57; 95% CI, 1.80–24.03; p=0.004) were independent risk factors for mortality within 30 days of CRV-LRDs. CONCLUSION: CRV-LRDs among SCT recipients showed substantially high morbidity and mortality rates. Therefore, the implement of an active diagnostic approaches for CRV infections is required for SCT recipients with respiratory symptoms, especially those receiving high-dose steroids or with lymphopenia.",2017 Mar 1,"['Hong, Kyung-Wook', 'Choi, Su-Mi', 'Lee, Dong-Gun', 'Cho, Sung-Yeon', 'Lee, Hyo-Jin', 'Choi, Jae-Ki', 'Kim, Si-Hyun', 'Park, Sun Hee', 'Choi, Jung-Hyun', 'Yoo, Jin-Hong', 'Lee, Jong-Wook']",Yonsei Med J,,,True
e4bd7b82d8631ca8edb9f41160a6a6094793964e,PMC,Publication of the Korea-WHO Cooperation History — 70 Years of Working Together for Heath: World Health Organization and the Republic of Korea,http://dx.doi.org/10.3346/jkms.2017.32.3.383,PMC5290094,28145638,CC BY-NC,"The World Health Organization (WHO) have been in collaborative efforts with the Republic of Korea in keeping of and for better health for all for the past decades. From the control of parasites to building of community health system in rural places, the works has now resulted in healthier Korea than ever, and has transformed the role of engaging as the world leader in contribution of health and development. Seventy years of independence, war, and poverty, transforming from a recipient country of official development assistance to a significant donor to the global society, we have emphasized the importance of international cooperation and the role of WHO in the past years in Korea and neighboring countries. Looking back of the past is meaningful to diagnose the present problems, and to foresee the future of our world.",2017 Mar 13,"['Cho, Heeyeon', 'Lee, Dong-woo', 'Choe, Young-June', 'Choe, Seung-Ah', 'Park, No-Yai']",J Korean Med Sci,,,True
64212980bf5953f369ec10e8a54517ec6ce10227,PMC,α2-Heremans-schmid glycoprotein (fetuin A) downregulation and its utility in inflammatory bowel disease,http://dx.doi.org/10.3748/wjg.v23.i3.437,PMC5291848,28210079,CC BY-NC,"AIM: To investigate the impact of inflammatory bowel disease (IBD) on α2-Heremans-Schmid Glycoprotein (AHSG/fetuin A) and potential associations with disease and patient characteristics. METHODS: AHSG serum levels were determined in treatment-naïve newly-diagnosed patients, 96 with ulcerative colitis (UC), 84 with Crohn's disease (CD), 62 with diarrhea-predominant or mixed irritable bowel syndrome (IBS, D- and M- types) and 180 healthy controls (HC), by an enzyme linked immunosorbent assay (ELISA). All patients were followed for a minimum period of 3 years at the Gastroenterology Department of the University Hospital of Larissa, Greece. C-reactive protein (CRP), anti-glycan antibodies, anti-Saccharomyces cerevisiae mannan antibodies IgG, anti-mannobioside carbohydrate antibodies IgG, anti-laminariobioside carbohydrate antibodies IgG and anti-chitobioside carbohydrate antibodies IgA were also determined via immunonephelometry and ELISA, respectively. RESULTS: The mean ± SE of serum AHSG, following adjustment for confounders, was 0.32 ± 0.02 g/L in IBD, 0.32 ± 0.03 g/L in CD and 0.34 ± 0.03 g/L in UC patients, significantly lower than in IBS patients (0.7 ± 0.018 g/L) and HC (0.71 ± 0.02 g/L) (P < 0.0001, in all cases). AHSG levels were comparable between the CD and UC groups. Based on AHSG levels IBD patients could be distinguished from HC with about 90% sensitivity and specificity. Further adjusted analysis verified the inverse association between AHSG and penetrating, as well as stricturing CD (partial correlation coefficient: -0.45 and -0.33, respectively) (P < 0.05). After adjusting for confounding factors, inverse correlations between AHSG and CRP and the need for anti-TNFα therapy or surgery, were found (partial correlation coefficients: -0.31, -0.33, -0.41, respectively, P < 0.05, in all cases). Finally, IBD individuals who were seropositive, for at least one marker, had AHSG levels falling within the two lower quartiles (OR = 2.86, 95%CI: 1.5-5.44, P < 0.001) while those with at least two serological markers positive exhibited AHSG concentrations within the lowest quartile (OR = 5.03, 95%CI: 2.07-12.21, P < 0.001), after adjusting for age, sex and smoking. CONCLUSION: AHSG can be used to distinguish between IBD and IBS patients or HC while at the same time ""predicting"" complicated disease behavior, need for therapy escalation and surgery. Moreover, AHSG may offer new insights into the pathogenesis of IBD, since it is involved in key processes.",2017 Jan 21,"['Manolakis, Anastassios C', 'Christodoulidis, Gregory', 'Kapsoritakis, Andreas N', 'Georgoulias, Panagiotis', 'Tiaka, Elisavet K', 'Oikonomou, Kostas', 'Valotassiou, Varvara J', 'Potamianos, Spyros P']",World J Gastroenterol,,,True
9f9984a45e51e8268ed00e6de9ca8b23615fb154,PMC,"Development of Dual TaqMan Based One-Step rRT-PCR Assay Panel for Rapid and Accurate Diagnostic Test of MERS-CoV: A Novel Human Coronavirus, Ahead of Hajj Pilgrimage",http://dx.doi.org/10.5812/ircmj.23874,PMC5292137,28191331,CC BY-NC,"BACKGROUND: Coronaviruses (CoVs) are large ribonucleic acid (RNA) viruses causing primarily respiratory disease in humans. A novel human coronavirus, subsequently named middle east respiratory syndrome coronavirus (MERS-CoV), was first reported in Saudi Arabia in September of 2012. With increasing numbers of infections and deaths from MERS-CoV, development of a rapid and reliable kit was crucial to prevent further spread of MERS-CoV. OBJECTIVES: In this study, we present two real-time reverse-transcription polymerase chain reaction (rRT-PCR) assays for in-house rapid and sensitive diagnostic testing of MERS-CoV, detecting the regions upstream of the envelope gene (upE) and open reading frame (ORF) 1b, respectively, for initial screening and final confirmation of MERS-CoV infection, as recommended by the world health organization (WHO). MATERIALS AND METHODS: In this experimental study, acquiring patient samples was difficult; thus, according to WHO recommendations and standard protocols, we synthesized RNA sequences of upE and ORF1b genes as the template signatures and TaqMan based-diagnostic rRT-PCR assays were carried out using these synthetic genes for detection of MERS-CoV. In this research, we also inaugurated a cell-free system to transcribe these RNA sequences using the DNA templates synthesized. RESULTS: The upE and ORF1b based one-step rRT-PCR assays were optimized by testing several times via different synthetic RNAs, and validation results were highly successful. The sensitivity obtained for upE was fewer than ten copies of RNA template per reaction and for ORF1b was 50 or fewer copies per reaction. CONCLUSIONS: This study showed that the developed rRT-PCR assays are rapid, reliable, reproducible, specific, sensitive, and simple tools for detection of MERS-CoV. Finally, a kit consisting of two assay signatures and controls was assembled, which can be distributed to public health laboratories in Iran to support international MERS-CoV surveillance and public health response.",2016 Jun 21,"['Hashemzadeh, Mohammad Sadegh', 'Rasouli, Rahimeh', 'Zahraei, Bentolhoda', 'Izadi, Morteza', 'Tat, Mahdi', 'Saadat, Seyed Hassan', 'Najarasl, Mohammad', 'Khansari Nejad, Behzad', 'Dorostkar, Ruhollah']",Iran Red Crescent Med J,,,True
d733c0afa475ed9c4f57c2540c0353d36cbc58e3,PMC,Complexity and Diversity of the Mammalian Sialome Revealed by Nidovirus Virolectins,http://dx.doi.org/10.1016/j.celrep.2015.05.044,PMC5292239,26095364,CC BY-NC-ND,"Sialic acids (Sias), 9-carbon-backbone sugars, are among the most complex and versatile molecules of life. As terminal residues of glycans on proteins and lipids, Sias are key elements of glycotopes of both cellular and microbial lectins and thus act as important molecular tags in cell recognition and signaling events. Their functions in such interactions can be regulated by post-synthetic modifications, the most common of which is differential Sia-O-acetylation (O-Ac-Sias). The biology of O-Ac-Sias remains mostly unexplored, largely because of limitations associated with their specific in situ detection. Here, we show that dual-function hemagglutinin-esterase envelope proteins of nidoviruses distinguish between a variety of closely related O-Ac-Sias. By using soluble forms of hemagglutinin-esterases as lectins and sialate-O-acetylesterases, we demonstrate differential expression of distinct O-Ac-sialoglycan populations in an organ-, tissue- and cell-specific fashion. Our findings indicate that programmed Sia-O-acetylation/de-O-acetylation may be critical to key aspects of cell development, homeostasis, and/or function.",2015 Jun 30,"['Langereis, Martijn A.', 'Bakkers, Mark J.G.', 'Deng, Lingquan', 'Padler-Karavani, Vered', 'Vervoort, Stephin J.', 'Hulswit, Ruben J.G.', 'van Vliet, Arno L.W.', 'Gerwig, Gerrit J.', 'de Poot, Stefanie A.H.', 'Boot, Willemijn', 'van Ederen, Anne Marie', 'Heesters, Balthasar A.', 'van der Loos, Chris M.', 'van Kuppeveld, Frank J.M.', 'Yu, Hai', 'Huizinga, Eric G.', 'Chen, Xi', 'Varki, Ajit', 'Kamerling, Johannis P.', 'de Groot, Raoul J.']",Cell Rep,,,True
8f05419fedcefa7d7f276b4ddebe1ad2fb363257,PMC,Complexity and Diversity of the Mammalian Sialome Revealed by Nidovirus Virolectins,http://dx.doi.org/10.1016/j.celrep.2015.05.044,PMC5292239,26095364,CC BY-NC-ND,"Sialic acids (Sias), 9-carbon-backbone sugars, are among the most complex and versatile molecules of life. As terminal residues of glycans on proteins and lipids, Sias are key elements of glycotopes of both cellular and microbial lectins and thus act as important molecular tags in cell recognition and signaling events. Their functions in such interactions can be regulated by post-synthetic modifications, the most common of which is differential Sia-O-acetylation (O-Ac-Sias). The biology of O-Ac-Sias remains mostly unexplored, largely because of limitations associated with their specific in situ detection. Here, we show that dual-function hemagglutinin-esterase envelope proteins of nidoviruses distinguish between a variety of closely related O-Ac-Sias. By using soluble forms of hemagglutinin-esterases as lectins and sialate-O-acetylesterases, we demonstrate differential expression of distinct O-Ac-sialoglycan populations in an organ-, tissue- and cell-specific fashion. Our findings indicate that programmed Sia-O-acetylation/de-O-acetylation may be critical to key aspects of cell development, homeostasis, and/or function.",2015 Jun 30,"['Langereis, Martijn A.', 'Bakkers, Mark J.G.', 'Deng, Lingquan', 'Padler-Karavani, Vered', 'Vervoort, Stephin J.', 'Hulswit, Ruben J.G.', 'van Vliet, Arno L.W.', 'Gerwig, Gerrit J.', 'de Poot, Stefanie A.H.', 'Boot, Willemijn', 'van Ederen, Anne Marie', 'Heesters, Balthasar A.', 'van der Loos, Chris M.', 'van Kuppeveld, Frank J.M.', 'Yu, Hai', 'Huizinga, Eric G.', 'Chen, Xi', 'Varki, Ajit', 'Kamerling, Johannis P.', 'de Groot, Raoul J.']",Cell Rep,,,True
b8664f2695036c9b4a78f07b4598f1f8d6f98386,PMC,Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome,http://dx.doi.org/10.5492/wjccm.v6.i1.85,PMC5295174,28224112,CC BY-NC,"We report a case of virus-induced acute respiratory distress syndrome (ARDS) treated with parenteral vitamin C in a patient testing positive for enterovirus/rhinovirus on viral screening. This report outlines the first use of high dose intravenous vitamin C as an interventional therapy for ARDS, resulting from enterovirus/rhinovirus respiratory infection. From very significant preclinical research performed at Virginia Commonwealth University with vitamin C and with the very positive results of a previously performed phase I safety trial infusing high dose vitamin C intravenously into patients with severe sepsis, we reasoned that infusing identical dosing to a patient with ARDS from viral infection would be therapeutic. We report here the case of a 20-year-old, previously healthy, female who contracted respiratory enterovirus/rhinovirus infection that led to acute lung injury and rapidly to ARDS. She contracted the infection in central Italy while on an 8-d spring break from college. During a return flight to the United States, she developed increasing dyspnea and hypoxemia that rapidly developed into acute lung injury that led to ARDS. When support with mechanical ventilation failed, extracorporeal membrane oxygenation (ECMO) was initiated. Twelve hours following ECMO initiation, high dose intravenous vitamin C was begun. The patient’s recovery was rapid. ECMO and mechanical ventilation were discontinued by day-7 and the patient recovered with no long-term ARDS sequelae. Infusing high dose intravenous vitamin C into this patient with virus-induced ARDS was associated with rapid resolution of lung injury with no evidence of post-ARDS fibroproliferative sequelae. Intravenous vitamin C as a treatment for ARDS may open a new era of therapy for ARDS from many causes.",2017 Feb 4,"['Fowler III, Alpha A', 'Kim, Christin', 'Lepler, Lawrence', 'Malhotra, Rajiv', 'Debesa, Orlando', 'Natarajan, Ramesh', 'Fisher, Bernard J', 'Syed, Aamer', 'DeWilde, Christine', 'Priday, Anna', 'Kasirajan, Vigneshwar']",World J Crit Care Med,,,True
31db09417c093cb1d87d4dfbbc2bef73716194e7,PMC,Interhospital Transport System for Critically Ill Patients: Mobile Extracorporeal Membrane Oxygenation without a Ventilator,http://dx.doi.org/10.5090/kjtcs.2017.50.1.8,PMC5295477,28180097,CC BY-NC,"BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been successfully used as a method for the interhospital transportation of critically ill patients. In South Korea, a well-established ECMO interhospital transport system is lacking due to limited resources. We developed a simplified ECMO transport system without mechanical ventilation for use by public emergency medical services. METHODS: Eighteen patients utilized our ECMO transport system from December 2011 to September 2015. We retrospectively analyzed the indications for ECMO, the patient status during transport, and the patient outcomes. RESULTS: All transport was conducted on the ground by ambulance. The distances covered ranged from 26 to 408 km (mean, 65.9±88.1 km) and the average transport time was 56.1±57.3 minutes (range, 30 to 280 minutes). All patients were transported without adverse events. After transport, 4 patients (22.2%) underwent lung transplantation because of interstitial lung disease. Eight patients who had severe acute respiratory distress syndrome showed recovery of heart and lung function after ECMO therapy. A total of 13 patients (70.6%) were successfully taken off ECMO, and 11 patients (61.1%) survived. CONCLUSION: Our ECMO transport system without mechanical ventilation can be considered a safe and useful method for interhospital transport and could be a good alternative option for ECMO transport in Korean hospitals with limited resources.",2017 Feb 5,"['Yeo, Hye Ju', 'Cho, Woo Hyun', 'Park, Jong Myung', 'Kim, Dohyung']",Korean J Thorac Cardiovasc Surg,,,True
ef4612cbe473c51bf23eafb3617692586c2d129c,PMC,The challenges of research nursing in an outbreak setting,http://dx.doi.org/10.1183/20734735.011616,PMC5298151,28210292,CC BY-NC,The challenges of research nursing in an outbreak setting http://ow.ly/jOFu301NzRh,2016 Sep,"Ferguson, Susie",Breathe (Sheff),,,False
d233d152df533dd90a4441a904c1652244ee5aaf,PMC,Clinical predictors of chest radiographic abnormalities in young children hospitalized with bronchiolitis: a single center study,http://dx.doi.org/10.3345/kjp.2016.59.12.471,PMC5300911,28194212,CC BY-NC,"PURPOSE: Chest radiography is often performed on patients hospitalized with typical clinical manifestations of bronchiolitis. We aimed to determine the proportion of subjects with pathologic chest radiographic findings and the clinical predictors associated with pathologic chest radiographic findings in young children admitted with the typical presentation of bronchiolitis. METHODS: We obtained the following data at admission: sex, age, neonatal history, past history of hospitalization for respiratory illnesses, heart rate, respiratory rate, the presence of fever, total duration of fever, oxygen saturation, laboratory parameters (i.e., complete blood cell count, high-sensitivity C-reactive protein [hs-CRP], etc.), and chest radiography. RESULTS: The study comprised 279 young children. Of these, 26 had a chest radiograph revealing opacity (n=24) or atelectasis (n=2). Multivariate logistic regression analysis showed that after adjustment for confounding factors, the clinical predictors associated with pathologic chest radiographic findings in young children admitted with bronchiolitis were elevated hs-CRP level (>0.3 mg/dL) and past history of hospitalization for respiratory illnesses (all P<0.05). CONCLUSION: The current study suggests that chest radiographs in young children with typical clinical manifestations of bronchiolitis have limited value. Nonetheless, young children with clinical factors such as high hs-CRP levels at admission or past history of hospitalization for respiratory illnesses may be more likely to have pathologic chest radiographic findings.",2016 Dec 31,"['Kim, Ga Ram', 'Na, Min Sun', 'Baek, Kyung Suk', 'Lee, Seung Jin', 'Lee, Kyung Suk', 'Jung, Young Ho', 'Jee, Hye Mi', 'Kwon, Tae Hee', 'Han, Man Yong', 'Sheen, Youn Ho']",Korean J Pediatr,,,True
38db3b3d3d82b08a9d95490fd0871d04d7001efe,PMC,Fall-related attendance and associated hospitalisation of children and adolescents in Hong Kong: a 12-year retrospective study,http://dx.doi.org/10.1136/bmjopen-2016-013724,PMC5306530,28174223,CC BY-NC,"OBJECTIVES: The present study aimed to examine the trends and characteristics of fall-related attendance in accident and emergency department (AED) by injury type and the trend in associated average length of stay (LOS) among children and adolescents in Hong Kong. DESIGN: A retrospective approach was adopted. SETTING: AED, involving all local public emergency departments from 2001 to 2012. PARTICIPANTS: 63 557 subjects aged 0–19 years with fall injury record were included in the analysis. PRIMARY OUTCOME MEASURES: Fall-related injury number and rates were calculated and reported. Poisson and negative binomial regression models were used to study the trends of injury incidence rate at different body regions. RESULTS: AED fall-related attendance rate increased significantly with an annual percentage change of 4.45 (95% CI 3.43 to 5.47%, p<0.0001). The attendance number of male subjects was persistently higher than female subjects. The standardised rate of fracture injury increased by 1.31% (95% CI 0.56 to 2.05%, p<0.0001) and that of non-fracture injury increased by 9.23% (95% CI 7.07 to 11.43%, p<0.0001) annually. Upper limb was the most frequently fractured location. It included forearm/elbow, shoulder/upper arm and wrist/hand with descending order of frequency. On the contrary, head was the most frequent non-fracture location, followed by forearm/elbow. CONCLUSIONS: The rates of fall-related attendance have been increasing and still remain high. There were significant increases in non-fracture injuries. Fractures were most frequently found in the upper extremity of a child while the most common non-fracture location was head. It appears that more efforts should be made and preventive measures should be implemented for children and adolescents in Hong Kong.",2017 Feb 7,"['Lee, James Chun-Yin', 'Tung, Keith Tsz-Suen', 'Li, Tim M H', 'Ho, Frederick Ka-Wing', 'Ip, Patrick', 'Wong, Wilfred Hing-Sang', 'Chow, Chun-Bong']",BMJ Open,,,True
1a2c142bc14744aa54241884929e8d18146de213,PMC,Fall-related attendance and associated hospitalisation of children and adolescents in Hong Kong: a 12-year retrospective study,http://dx.doi.org/10.1136/bmjopen-2016-013724,PMC5306530,28174223,CC BY-NC,"OBJECTIVES: The present study aimed to examine the trends and characteristics of fall-related attendance in accident and emergency department (AED) by injury type and the trend in associated average length of stay (LOS) among children and adolescents in Hong Kong. DESIGN: A retrospective approach was adopted. SETTING: AED, involving all local public emergency departments from 2001 to 2012. PARTICIPANTS: 63 557 subjects aged 0–19 years with fall injury record were included in the analysis. PRIMARY OUTCOME MEASURES: Fall-related injury number and rates were calculated and reported. Poisson and negative binomial regression models were used to study the trends of injury incidence rate at different body regions. RESULTS: AED fall-related attendance rate increased significantly with an annual percentage change of 4.45 (95% CI 3.43 to 5.47%, p<0.0001). The attendance number of male subjects was persistently higher than female subjects. The standardised rate of fracture injury increased by 1.31% (95% CI 0.56 to 2.05%, p<0.0001) and that of non-fracture injury increased by 9.23% (95% CI 7.07 to 11.43%, p<0.0001) annually. Upper limb was the most frequently fractured location. It included forearm/elbow, shoulder/upper arm and wrist/hand with descending order of frequency. On the contrary, head was the most frequent non-fracture location, followed by forearm/elbow. CONCLUSIONS: The rates of fall-related attendance have been increasing and still remain high. There were significant increases in non-fracture injuries. Fractures were most frequently found in the upper extremity of a child while the most common non-fracture location was head. It appears that more efforts should be made and preventive measures should be implemented for children and adolescents in Hong Kong.",2017 Feb 7,"['Lee, James Chun-Yin', 'Tung, Keith Tsz-Suen', 'Li, Tim M H', 'Ho, Frederick Ka-Wing', 'Ip, Patrick', 'Wong, Wilfred Hing-Sang', 'Chow, Chun-Bong']",BMJ Open,,,False
8fec2036fb2e98cbb9d4f955ce1d5198d1a09b3c,PMC,Unreported intrinsic disorder in proteins: Building connections to the literature on IDPs,http://dx.doi.org/10.4161/21690693.2014.970499,PMC5314882,28232880,CC BY-NC,"This review opens a new series entitled “Unreported intrinsic disorder in proteins.” The goal of this series is to bring attention of researchers to an interesting phenomenon of missed (or overlooked, or ignored, or unreported) disorder. This series serves as a companion to “Digested Disorder” which provides a quarterly review of papers on intrinsically disordered proteins (IDPs) found by standard literature searches. The need for this alternative series results from the observation that there are numerous publications that describe IDPs (or hybrid proteins with ordered and disordered regions) yet fail to recognize many of the key discoveries and publications in the IDP field. By ignoring the body of work on IDPs, such publications often fail to relate their findings to prior discoveries or fail to explore the obvious implications of their work. Thus, the goal of this series is not only to review these very interesting and important papers, but also to point out how each paper relates to the IDP field and show how common tools in the IDP field can readily take the findings in new directions or provide a broader context for the reported findings.",2014 Dec 12,"Uversky, Vladimir N",Intrinsically Disord Proteins,,,True
a6604f5c880a6a511053e91df3800780cdc3a876,PMC,Examining the relationship between infectious diseases and flooding in Europe: A systematic literature review and summary of possible public health interventions,http://dx.doi.org/10.4161/dish.25216,PMC5314884,28228994,CC BY-NC,"Introduction Many infectious diseases are sensitive to climatic changes; specifically, flooding. This systematic literature review aimed to strengthen the quality and completeness of evidence on infectious diseases following flooding, relevant to Europe. Methods A systematic literature review from 2004–2012 was performed. Focused searches of the following databases were conducted: Medline, Scopus, PubMed, Cochrane Library, and Evidence Aid. Personal communications with key informants were also reviewed. Results Thirty-eight studies met the inclusion criteria. Evidence suggested that water-borne, rodent-borne, and vector-borne diseases have been associated with flooding in Europe, although at a lower incidence than developing countries. Conclusion Disease surveillance and early warning systems, coupled with effective prevention and response capabilities, can reduce current and future vulnerability to infectious diseases following flooding.",2013 Apr 1,"['Brown, Lisa', 'Murray, Virginia']",Disaster Health,,,True
f084dcc7e442ab282deb97670e1843e347cf1fd5,PMC,"Ebola Holding Units at government hospitals in Sierra Leone: evidence for a flexible and effective model for safe isolation, early treatment initiation, hospital safety and health system functioning",http://dx.doi.org/10.1136/bmjgh-2016-000030,PMC5321322,28588922,CC BY-NC,"The 2014-2015 West African outbreak of Ebola Virus Disease (EVD) claimed the lives of more than 11,000 people and infected over 27,000 across seven countries. Traditional approaches to containing EVD proved inadequate and new approaches for controlling the outbreak were required. The Ministry of Health & Sanitation and King’s Sierra Leone Partnership developed a model for Ebola Holding Units (EHUs) at Government Hospitals in the capital city Freetown. The EHUs isolated screened or referred suspect patients, provided initial clinical care, undertook laboratory testing to confirm EVD status, referred onward positive cases to an Ebola Treatment Centre or negative cases to the general wards, and safely stored corpses pending collection by burial teams. Between 29th May 2014 and 19th January 2015, our five units had isolated approximately 37% (1159) of the 3097 confirmed cases within Western Urban and Rural district. Nosocomial transmission of EVD within the units appears lower than previously documented at other facilities and staff infection rates were also low. We found that EHUs are a flexible and effective model of rapid diagnosis, safe isolation and early initial treatment. We also demonstrated that it is possible for international partners and government facilities to collaborate closely during a humanitarian crisis.",2016 Jun 9,"['Johnson, Oliver', 'Youkee, Daniel', 'Brown, Colin S', 'Lado, Marta', 'Wurie, Alie', 'Bash-Taqi, Donald', 'Hall, Andy', 'Hanciles, Eva', 'Kamara, Isata', 'Kamara, Cecilia', 'Kamboz, Amardeep', 'Seedat, Ahmed', 'Thomas, Suzanne', 'Kamara, T B', 'Leather, Andrew J M', 'Kargbo, Brima']",BMJ Glob Health,,,True
5a9de698acd2aea68074eb45c0925d4377a41011,PMC,Community health workers in Ghana: the need for greater policy attention,http://dx.doi.org/10.1136/bmjgh-2016-000141,PMC5321387,28588981,CC BY-NC,"From the 1970s to the 1990s, the WHO, United Nations and other agencies mooted the idea of formally training and recognising community health workers (CHWs) to complement efforts to improve primary healthcare delivery in low and middle income countries. Recently, CHWs have been recognised as important players in the achievement of the health-related Millennium Development Goals (MDGs). Despite this recognition, little understanding exists in Ghana about the activities of CHWs: who they are; how they are recruited; what they do; level of health policy support; contribution to healthcare delivery and the challenges they face. Based on a rapid scoping review of the existing literature, and our experience working in Ghana, this paper reflects on the role of CHWs in healthcare delivery in Ghana. We argue that CHWs have played critical roles in improving health service delivery and outcomes, including guinea worm eradication, expanded immunisation coverage, maternal and child health, and HIV/AIDS treatment and management. However, these achievements notwithstanding, CHWs face challenges which prevent them from being optimally productive, including capacity problems, neglect by the healthcare system, high attrition rates and inadequate supervision. Policymakers in Ghana therefore need to give increased attention to CHWs, provide remuneration for their activities, create career opportunities and other means of motivations to boost their productivity and sustain gains associated with their activities.",2016 Dec 2,"['Baatiema, Leonard', 'Sumah, Anthony Mwinkaara', 'Tang, Prosper Naazumah', 'Ganle, John Kuumuori']",BMJ Glob Health,,,True
e0875b937adb61d120554efed78760b89fda64b8,PMC,Characterization of canine coronavirus spread among domestic dogs in Vietnam,http://dx.doi.org/10.1292/jvms.16-0538,PMC5326940,27840394,CC BY-NC-ND,"Canine coronavirus (CCoV) is an important pathogen that causes enteritis in dogs, but there is no information on CCoV infection in Vietnam. To examine the prevalence of CCoV infection among Vietnamese dogs, 201 serum samples were analyzed by virus-neutralization (VN) test. The results showed that antibody against CCoV-II was present in 87 dogs (43.3%). To detect genes of CCoV, fecal samples collected from 30 diarrheic and 50 healthy dogs were examinated by RT-PCR, confirming that 2 diarrheic dogs and 5 healthy dogs were positive for CCoV. Nucleotide sequences of N-terminal region of spike (S) gene indicated that CCoV strains were divided into two subgenotypes, CCoV-IIa and -IIb, respectively. Furthemore, we succeeded in isolating CCoV/dog/HCM47/2015, the isolate was plaque-purified three times, and 3’-terminal one-third of the genome was analyzed. Interestingly, the plaque-purified virus had a large deletion in ORF3abc and E genes (1,165 nt), and a short deletion in ORF7b gene (60 nt), suggesting that these regions are not necessary for in vitro replication of CCoV. Next, the antigenicity between the isolated CCoV-IIb and the other CCoV-IIa was compared by VN test, revealing that antigenicty of the isolated CCoV is equal or higher than that of the other CCoV. In summary, two subgenotypes of CCoV-II are spreading among Vietnamese dogs. The isolated virus with a large deletion after in vitro passage may be useful for the development of vaccine, owing to its antigenicity and efficient viral growth in vitro.",2017 Feb 14,"['van NGUYEN, Dung', 'TERADA, Yukata', 'MINAMI, Shohei', 'YONEMITSU, Kenzo', 'NAGATA, Nao', 'LE, Thanh Dinh Ha', 'KUWATA, Ryusei', 'SHIMODA, Hiroshi', 'MAEDA, Ken']",J Vet Med Sci,,,True
e79419067a6b140a71e7a89e5a275ce2bf89ac35,PMC,Characterization of canine coronavirus spread among domestic dogs in Vietnam,http://dx.doi.org/10.1292/jvms.16-0538,PMC5326940,27840394,CC BY-NC-ND,"Canine coronavirus (CCoV) is an important pathogen that causes enteritis in dogs, but there is no information on CCoV infection in Vietnam. To examine the prevalence of CCoV infection among Vietnamese dogs, 201 serum samples were analyzed by virus-neutralization (VN) test. The results showed that antibody against CCoV-II was present in 87 dogs (43.3%). To detect genes of CCoV, fecal samples collected from 30 diarrheic and 50 healthy dogs were examinated by RT-PCR, confirming that 2 diarrheic dogs and 5 healthy dogs were positive for CCoV. Nucleotide sequences of N-terminal region of spike (S) gene indicated that CCoV strains were divided into two subgenotypes, CCoV-IIa and -IIb, respectively. Furthemore, we succeeded in isolating CCoV/dog/HCM47/2015, the isolate was plaque-purified three times, and 3’-terminal one-third of the genome was analyzed. Interestingly, the plaque-purified virus had a large deletion in ORF3abc and E genes (1,165 nt), and a short deletion in ORF7b gene (60 nt), suggesting that these regions are not necessary for in vitro replication of CCoV. Next, the antigenicity between the isolated CCoV-IIb and the other CCoV-IIa was compared by VN test, revealing that antigenicty of the isolated CCoV is equal or higher than that of the other CCoV. In summary, two subgenotypes of CCoV-II are spreading among Vietnamese dogs. The isolated virus with a large deletion after in vitro passage may be useful for the development of vaccine, owing to its antigenicity and efficient viral growth in vitro.",2017 Feb 14,"['van NGUYEN, Dung', 'TERADA, Yukata', 'MINAMI, Shohei', 'YONEMITSU, Kenzo', 'NAGATA, Nao', 'LE, Thanh Dinh Ha', 'KUWATA, Ryusei', 'SHIMODA, Hiroshi', 'MAEDA, Ken']",J Vet Med Sci,,,False
4aa30aa1b955b36fda673d75c1a37f386f5823c4,PMC,Spontaneous intracranial hemorrhage in a patient with Middle East respiratory syndrome corona virus,http://dx.doi.org/10.15537/smj.2017.2.16255,PMC5329633,28133694,CC BY-NC-SA,"The Middle East respiratory syndrome corona virus (MERS-CoV) is a novel positive sense singlestranded ribonucleic acid virus of the genus Beta corona virus. This virus was first isolated from a patient who died from severe respiratory illness in June 2012 in Jeddah, Kingdom of Saudi Arabia. We describe an unusual case of a 42 year old healthcare worker who was admitted to our Intensive Care Unit (ICU) King Abdul-Aziz Medical City, with MERS-CoV and severe acute respiratory distress Syndrome and developed a sudden-onset diabetes insipidus and spontaneous massive intracranial hemorrhage with intra-ventricular extension and tonsillar herniation. Computed angiogram of the brain did not reveal any aneurysm or structural defects. She never had uncontrolled hypertension, or coagulopathy, nor she received antiplatelets. We are reporting a rare case of structural neurological damage associated with MERS-CoV infection.",2017 Feb,"Al-Hameed, Fahad M.",Saudi Med J,,,True
fac313563bd7a9ff7bb33495d81086ca75615951,PMC,Implementing One Health as an integrated approach to health in Rwanda,http://dx.doi.org/10.1136/bmjgh-2016-000121,PMC5335763,28588996,CC BY-NC,"It is increasingly clear that resolution of complex global health problems requires interdisciplinary, intersectoral expertise and cooperation from governmental, non-governmental and educational agencies. ‘One Health’ refers to the collaboration of multiple disciplines and sectors working locally, nationally and globally to attain optimal health for people, animals and the environment. One Health offers the opportunity to acknowledge shared interests, set common goals, and drive toward team work to benefit the overall health of a nation. As in most countries, the health of Rwanda's people and economy are highly dependent on the health of the environment. Recently, Rwanda has developed a One Health strategic plan to meet its human, animal and environmental health challenges. This approach drives innovations that are important to solve both acute and chronic health problems and offers synergy across systems, resulting in improved communication, evidence-based solutions, development of a new generation of systems-thinkers, improved surveillance, decreased lag time in response, and improved health and economic savings. Several factors have enabled the One Health movement in Rwanda including an elaborate network of community health workers, existing rapid response teams, international academic partnerships willing to look more broadly than at a single disease or population, and relative equity between female and male health professionals. Barriers to implementing this strategy include competition over budget, poor communication, and the need for improved technology. Given the interconnectedness of our global community, it may be time for countries and their neighbours to follow Rwanda's lead and consider incorporating One Health principles into their national strategic health plans.",2017 Feb 21,"['Nyatanyi, Thierry', 'Wilkes, Michael', 'McDermott, Haley', 'Nzietchueng, Serge', 'Gafarasi, Isidore', 'Mudakikwa, Antoine', 'Kinani, Jean Felix', 'Rukelibuga, Joseph', 'Omolo, Jared', 'Mupfasoni, Denise', 'Kabeja, Adeline', 'Nyamusore, Jose', 'Nziza, Julius', 'Hakizimana, Jean Leonard', 'Kamugisha, Julius', 'Nkunda, Richard', 'Kibuuka, Robert', 'Rugigana, Etienne', 'Farmer, Paul', 'Cotton, Philip', 'Binagwaho, Agnes']",BMJ Glob Health,,,True
4a1b2f689df4d8dd7521873bf16eed8523cf968d,PMC,Implementing One Health as an integrated approach to health in Rwanda,http://dx.doi.org/10.1136/bmjgh-2016-000121,PMC5335763,28588996,CC BY-NC,"It is increasingly clear that resolution of complex global health problems requires interdisciplinary, intersectoral expertise and cooperation from governmental, non-governmental and educational agencies. ‘One Health’ refers to the collaboration of multiple disciplines and sectors working locally, nationally and globally to attain optimal health for people, animals and the environment. One Health offers the opportunity to acknowledge shared interests, set common goals, and drive toward team work to benefit the overall health of a nation. As in most countries, the health of Rwanda's people and economy are highly dependent on the health of the environment. Recently, Rwanda has developed a One Health strategic plan to meet its human, animal and environmental health challenges. This approach drives innovations that are important to solve both acute and chronic health problems and offers synergy across systems, resulting in improved communication, evidence-based solutions, development of a new generation of systems-thinkers, improved surveillance, decreased lag time in response, and improved health and economic savings. Several factors have enabled the One Health movement in Rwanda including an elaborate network of community health workers, existing rapid response teams, international academic partnerships willing to look more broadly than at a single disease or population, and relative equity between female and male health professionals. Barriers to implementing this strategy include competition over budget, poor communication, and the need for improved technology. Given the interconnectedness of our global community, it may be time for countries and their neighbours to follow Rwanda's lead and consider incorporating One Health principles into their national strategic health plans.",2017 Feb 21,"['Nyatanyi, Thierry', 'Wilkes, Michael', 'McDermott, Haley', 'Nzietchueng, Serge', 'Gafarasi, Isidore', 'Mudakikwa, Antoine', 'Kinani, Jean Felix', 'Rukelibuga, Joseph', 'Omolo, Jared', 'Mupfasoni, Denise', 'Kabeja, Adeline', 'Nyamusore, Jose', 'Nziza, Julius', 'Hakizimana, Jean Leonard', 'Kamugisha, Julius', 'Nkunda, Richard', 'Kibuuka, Robert', 'Rugigana, Etienne', 'Farmer, Paul', 'Cotton, Philip', 'Binagwaho, Agnes']",BMJ Glob Health,,,False
106203869ac3c318d5ec8a2644d469d71e98f056,PMC,Cardiac problem and MERS,http://dx.doi.org/10.5152/AnatolJCardiol.2015.6602,PMC5336990,26477731,CC BY-NC-SA,,2015 Oct,"Wiwanitkit, Viroj",Anatol J Cardiol,,,True
58c87ea90b23dc0d106427b76bb5525b6aa01b77,PMC,Interstitial Pneumonia Associated with the Influenza Vaccine: A Report of Two Cases,,PMC5337467,28090052,CC BY-NC-ND,"Although the influenza vaccine is relatively safe and effective, serious complications can develop in rare cases. We encountered two cases of interstitial pneumonia that developed after vaccination during the 2014-2015 influenza season. Overall, nine cases, including the two presented here, have been recorded in PubMed and the Cochrane library; eight patients were treated with corticosteroids, and all nine survived, suggesting a good prognosis. Interstitial pneumonia is rare; however, we found an increase in its incidence after 2009. Therefore, clinicians must be aware of the possibility of this complication and duly educate all patients in advance.",2017 Jan 15,"['Hibino, Makoto', 'Kondo, Tetsuri']",Intern Med,,,True
5856a3f4b9fc9b0947bf045feb20d32d581221dc,PMC,"Amylmetacresol/2,4-dichlorobenzyl alcohol, hexylresorcinol, or carrageenan lozenges as active treatments for sore throat",http://dx.doi.org/10.2147/IJGM.S120665,PMC5339006,28280379,CC BY-NC,"Up to 80% of sore throats are caused by viruses. Several over the counter products are available which provide symptomatic, not causal relief. For such lozenges, containing the antiseptics and local anesthetics amylmetacresol (AMC) and 2,4-dichlorobenzyl alcohol (DCBA) or hexylresorcinol (HR), recently an additional virucidal effect was published. Therefore, we tested a set of Strepsils(®) lozenges, containing either HR (Max [#2]) or AMC/DCBA (Original [#3], Extra Strong [#4], Warm [#5], Orange and Vitamin C [#6], Sugar free Lemon [#7], Children/Strawberry [#8] and Soothing Honey and Lemon [#9]) for their antiviral efficiency against representatives of respiratory viruses known to cause sore throat: human rhinovirus (HRV) 1a, HRV8, influenza virus A H1N1n, Coxsackievirus A10, and human coronavirus (hCoV) OC43. The lozenges were tested head to head with Coldamaris(®) lozenges (#1), which contain the patented antiviral iota-carrageenan. None of the tested AMC/DCBA or HR containing lozenges shows any antiviral effectiveness against HRV8 at the tested concentrations, whereas all are moderately active against HRV1a. Only lozenge #5 shows any activity against hCoV OC43 and Coxsackievirus A10 at the tested concentrations. Similarly, only lozenge #3 is moderately active against influenza A H1N1n virus. The data indicates that neither the isolated effect of the active ingredients nor the pH but rather one or more of the excipients of the specific formulations are responsible for the antiviral effect of some of the AMC/DCBA or HR containing lozenges. In contrast, carrageenan-containing lozenges are highly active against all viruses tested. In another experiment, we showed that binding and inactivation of virus particles by iota-carrageenan are fast and highly effective. During the residence time of the lozenge in the mouth, the viral titer is reduced by 85% and 91% for influenza A virus and hCoV OC43, respectively. Carrageenan-containing lozenges are, therefore, suitable as causative therapy against viral infections of the throat.",2017 Feb 28,"['Morokutti-Kurz, Martina', 'Graf, Christine', 'Prieschl-Grassauer, Eva']",Int J Gen Med,,,True
15ac0bdac1ae44bf9d833b2156761082915fb642,PMC,Comparison of Luminex NxTAG Respiratory Pathogen Panel and xTAG Respiratory Viral Panel FAST Version 2 for the Detection of Respiratory Viruses,http://dx.doi.org/10.3343/alm.2017.37.3.267,PMC5339100,28224774,CC BY-NC,"Owing to advancements in molecular diagnostics, recent years have seen an increasing number of laboratories adopting respiratory viral panels to detect respiratory pathogens. In December 2015, the NxTAG respiratory pathogen panel (NxTAG RPP) was approved by the United States Food and Drug Administration. We compared the clinical performance of this new assay with that of the xTAG respiratory viral panel (xTAG RVP) FAST v2 using 142 clinical samples and 12 external quality assessment samples. Discordant results were resolved by using a laboratory-developed respiratory viral panel. The NxTAG RPP achieved 100% concordant negative results and 86.6% concordant positive results. It detected one coronavirus 229E and eight influenza A/H3N2 viruses that were missed by the xTAG RVP FAST v2. On the other hand, the NxTAG RPP missed one enterovirus/rhinovirus and one metapneumovirus that were detected by FAST v2. Both panels correctly identified all the pathogens in the 12 external quality assessment samples. Overall, the NxTAG RPP demonstrated good diagnostic performance. Of note, it was better able to subtype the influenza A/H3N2 viruses compared with the xTAG RVP FAST v2.",2017 May 17,"['Lee, Chun Kiat', 'Lee, Hong Kai', 'Ng, Christopher Wei Siong', 'Chiu, Lily', 'Tang, Julian Wei-Tze', 'Loh, Tze Ping', 'Koay, Evelyn Siew-Chuan']",Ann Lab Med,,,True
eee528b0235a1312f9d280b603d91e241a38bb40,PMC,Comparison of Luminex NxTAG Respiratory Pathogen Panel and xTAG Respiratory Viral Panel FAST Version 2 for the Detection of Respiratory Viruses,http://dx.doi.org/10.3343/alm.2017.37.3.267,PMC5339100,28224774,CC BY-NC,"Owing to advancements in molecular diagnostics, recent years have seen an increasing number of laboratories adopting respiratory viral panels to detect respiratory pathogens. In December 2015, the NxTAG respiratory pathogen panel (NxTAG RPP) was approved by the United States Food and Drug Administration. We compared the clinical performance of this new assay with that of the xTAG respiratory viral panel (xTAG RVP) FAST v2 using 142 clinical samples and 12 external quality assessment samples. Discordant results were resolved by using a laboratory-developed respiratory viral panel. The NxTAG RPP achieved 100% concordant negative results and 86.6% concordant positive results. It detected one coronavirus 229E and eight influenza A/H3N2 viruses that were missed by the xTAG RVP FAST v2. On the other hand, the NxTAG RPP missed one enterovirus/rhinovirus and one metapneumovirus that were detected by FAST v2. Both panels correctly identified all the pathogens in the 12 external quality assessment samples. Overall, the NxTAG RPP demonstrated good diagnostic performance. Of note, it was better able to subtype the influenza A/H3N2 viruses compared with the xTAG RVP FAST v2.",2017 May 17,"['Lee, Chun Kiat', 'Lee, Hong Kai', 'Ng, Christopher Wei Siong', 'Chiu, Lily', 'Tang, Julian Wei-Tze', 'Loh, Tze Ping', 'Koay, Evelyn Siew-Chuan']",Ann Lab Med,,,False
92aca69f518fc394bd00b525898264893d9550af,PMC,Interferon-Stimulated Gene 15 in the Control of Cellular Responses to Genotoxic Stress,http://dx.doi.org/10.14348/molcells.2017.0027,PMC5339507,28241406,CC BY-NC-SA,"Error-free replication and repair of DNA are pivotal to organisms for faithful transmission of their genetic information. Cells orchestrate complex signaling networks that sense and resolve DNA damage. Post-translational protein modifications by ubiquitin and ubiquitin-like proteins, including SUMO and NEDD8, are critically involved in DNA damage response (DDR) and DNA damage tolerance (DDT). The expression of interferon-stimulated gene 15 (ISG15), the first identified ubiquitin-like protein, has recently been shown to be induced under various DNA damage conditions, such as exposure to UV, camptothecin, and doxorubicin. Here we overview the recent findings on the role of ISG15 and its conjugation to target proteins (e.g., p53, ΔNp63α, and PCNA) in the control of cellular responses to genotoxic stress, such as the inhibition of cell growth and tumorigenesis.",2017 Feb 28,"['Jeon, Young Joo', 'Park, Jong Ho', 'Chung, Chin Ha']",Mol Cells,,,True
21a164b5e3d241d8d34eb335bf8db56dc945fea6,PMC,Assessing Continuous Quality Improvement in Public Health: Adapting Lessons from Healthcare,,PMC5344362,28277203,CC BY-NC,"CONTEXT: Evidence of the effect of continuous quality improvement (CQI) in public health and valid tools to judge that such effects are not fully formed. OBJECTIVE: The objective was to adapt and apply Shortell et al.'s (1998) four dimensions of CQI in an examination of a public health accountability and performance management initiative in Ontario, Canada. METHODS: In total, 24 semi-structured, in-depth interviews were conducted with informants from public health units and the Ministry of Health and Long-Term Care. A web survey of public health managers in the province was also carried out. RESULTS: A mix of facilitators and barriers was identified. Leadership and organizational cultures, conducive to CQI success were evident. However, limitations in performance measurement and managerial discretion were key barriers. CONCLUSION: The four dimensions of CQI provided insight into both facilitators and barriers of CQI adoption in public health. Future research should compare the outcomes of public health CQI initiatives to the framework's stated facilitators and barriers.",2017 Feb,"['Price, Alex', 'Schwartz, Robert', 'Cohen, Joanna', 'Manson, Heather', 'Scott, Fran']",Healthc Policy,,,True
a40363fa5527e9b6dbf6930b247a4608027e7983,PMC,Aspirin Intolerance: Experimental Models for Bed-to-Bench,http://dx.doi.org/10.2174/1389450117666161005152327,PMC5345322,27719658,CC BY-NC,"Aspirin is the oldest non-steroidal anti-inflammatory drug (NSAID), and it sometimes causes asthma-like symptoms known as aspirin-exacerbated respiratory disease (AERD), which can be serious. Unwanted effects of aspirin (aspirin intolerance) are also observed in patients with food-dependent exercise-induced anaphylaxis, a type I allergy disease, and aspirin-induced urticaria (AIU). However the target and the mechanism of the aspirin intolerance are still unknown. There is no animal or cellular model of AERD, because its pathophysiological mechanism is still unknown, but it is thought that inhibition of cyclooxygenase by causative agents leads to an increase of free arachidonic acid, which is metabolized into cysteinyl leukotrienes (cysLTs) that provoke airway smooth muscle constriction and asthma symptoms. As the bed-to-bench approach, to confirm the clinical discussion in experimental cellular models, we have tried to develop a cellular model of AERD using activated RBL-2H3 cells, a rat mast cell like cell line. Indomethacin (another NSAID and also causes AERD), enhances in vitro cysLTs production by RBL-2H3 cells, while there is no induction of cysLTs production in the absence of inflammatory activation. Since this suggests that all inflammatory cells with activation of prostaglandin and cysLT metabolism should respond to NSAIDs, and then I have concluded that aspirin intolerance should be separated from subsequent bronchoconstriction. Evidence about the cellular mechanisms of NSAIDs may be employed for development of in vitro AERD models as the approach from bench-to-bed.",2016 Dec,"Yamashita, Masamichi",Curr Drug Targets,,,True
d5b981ab9223ede1243af2a7030ced8570c82edc,PMC,"Ebola Viral Disease in West Africa: A Threat to Global Health, Economy and Political Stability",http://dx.doi.org/10.4081/jphia.2016.534,PMC5349256,28299152,CC BY-NC,"The West African sub-continent is currently experiencing its first, and ironically, the largest and longest Ebola viral diseases (EVD) outbreak ever documented in modern medical history. The current outbreak is significant in several ways, including longevity, magnitude of morbidity and mortality, occurrence outside the traditional niches, rapid spread and potential of becoming a global health tragedy. The authors provided explicit insights into the current and historical background, drivers of the epidemic, societal impacts, status of vaccines and drugs development and proffered recommendations to halt and prevent future occurrences. The authors reviewed mainly five databases and a hand search of key relevant literature. We reviewed 51 articles that were relevant up until the 18(th) of August 2014. The authors supplemented the search with reference list of relevant articles and grey literature as well as relevant Internet websites. Article searches were limited to those published either in English or French. There are strong indications that the EVD may have been triggered by increased human activities and encroachment into the forest ecosystem spurred by increasing population and poverty-driven forest-dependent local economy. Containment efforts are being hampered by weak and fragile health systems, including public health surveillance and weak governance, certain socio-anthropological factors, fast travels (improved transport systems) and globalization. The societal impacts of the EBV outbreak are grave, including economic shutdown, weakening of socio-political systems, psychological distress, and unprecedented consumption of scarce health resources. The research and development (R&D) pipeline for product against EBV seems grossly insufficient. The outbreak of Ebola and the seeming difficulty to contain the epidemic is simply a reflection of the weak health system, poor surveillance and emergency preparedness/response, poverty and disconnect between the government and the people in many West African countries. Although interventions by the United Nations and other international development agencies could ultimately halt the epidemic, local communities must be engaged to build trust and create demand for the public health interventions being implemented in the Ebola-ravaged populations. In the intermediate and long term, post-Ebola rehabilitation should focus on strengthening of health systems, improving awareness about zoonosis and health behaviors, alleviating poverty and mitigating the impact of triggering factors. Finally, national governments and international development partners should mobilize huge resources and investments to spur or facilitate R&D of disease control tools for emerging and pernicious infectious diseases (not limited to EVD).",2016 Aug 17,"['Omoleke, Semeeh Akinwale', 'Mohammed, Ibrahim', 'Saidu, Yauba']",J Public Health Africa,,,True
ee106840a4b1667303e4b84d25795de3617bd7ef,PMC,Environmental triggers and avoidance in the management of asthma,http://dx.doi.org/10.2147/JAA.S121276,PMC5349698,28331347,CC BY-NC,"Identifying asthma triggers forms the basis of environmental secondary prevention. These triggers may be allergenic or nonallergenic. Allergenic triggers include indoor allergens, such as house dust mites (HDMs), molds, pets, cockroaches, and rodents, and outdoor allergens, such as pollens and molds. Clinical observations provide support for the role of HDM exposure as a trigger, although avoidance studies provide conflicting results. Molds and their metabolic products are now considered to be triggers of asthma attacks. Pets, dogs, and especially cats can undoubtedly trigger asthmatic symptoms in sensitized subjects. Avoidance is difficult and rarely adhered to by families. Cockroach allergens contribute to asthma morbidity, and avoidance strategies can lead to clinical benefit. Mouse allergens are mostly found in inner-city dwellings, but their implication in asthma morbidity is debated. In the outdoors, pollens can induce seasonal asthma in sensitized individuals. Avoidance relies on preventing pollens from getting into the house and on minimizing seasonal outdoor exposure. Outdoor molds may lead to severe asthma exacerbations. Nonallergenic triggers include viral infections, active and passive smoking, meteorological changes, occupational exposures, and other triggers that are less commonly involved. Viral infection is the main asthma trigger in children. Active smoking is associated with higher asthma morbidity, and smoking cessation interventions should be personalized. Passive smoking is also a risk factor for asthma exacerbation. The implementation of public smoking bans has led to a reduction in the hospitalization of asthmatic children. Air pollution levels have been linked with asthmatic symptoms, a decrease in lung function, and increased emergency room visits and hospitalizations. Since avoidance is not easy to achieve, clean air policies remain the most effective strategy. Indoor air is also affected by air pollutants, such as cigarette smoke and volatile organic compounds generated by building and cleaning materials. Occupational exposures include work-exacerbated asthma and work-related asthma.",2017 Mar 7,"['Gautier, Clarisse', 'Charpin, Denis']",J Asthma Allergy,,,True
4135ace30ea08a669730959e0f98a4af06537d07,PMC,Surveillance of Australian Hajj pilgrims for carriage of potentially pathogenic bacteria: Data from two pilot studies,http://dx.doi.org/10.12998/wjcc.v5.i3.102,PMC5352958,28352634,CC BY-NC,"AIM: To estimate the pharyngeal carriage rate of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae) and Staphylococcus aureus (S. aureus) among Australian Hajj pilgrims. METHODS: In 2014, surveillance was conducted in two phases among Australian Hajj pilgrims: The first phase during Hajj in Mina, and the second phase soon after returning home to Australia. Nasopharyngeal or oropharyngeal swabs were taken from participants then tested, firstly by nucleic acid testing, and also by standard culture. RESULTS: Of 183 participants recruited in the first phase, 26 (14.2%) tested positive for S. pneumoniae; 4 had received pneumococcal conjugate vaccine (PCV13). Only one tested positive for N. meningitidis (W). Of 93 2(nd) phase samples cultured, 17 (18.3%) grew S. aureus, all methicillin sensitive, 2 (2.2%) grew N. meningitidis (on subculture; one serotype B, one negative), and 1 (1%), from an unvaccinated pilgrim, grew S. pneumoniae. CONCLUSION: Relatively high carriage of S. pneumoniae and little meningococcal carriage was found. This indicates the importance of a larger study for improved infection surveillance and possible vaccine evaluation.",2017 Mar 16,"['Azeem, Mohammad Irfan', 'Tashani, Mohamed', 'Badahdah, Al-Mamoon', 'Heron, Leon', 'Pedersen, Kristen', 'Jeoffreys, Neisha', 'Kok, Jen', 'Haworth, Elizabeth', 'Dwyer, Dominic E', 'Hill-Cawthorne, Grant', 'Rashid, Harunor', 'Booy, Robert']",World J Clin Cases,,,True
bab279da548d8bd363acd5033e9dc54e7dbb7107,PMC,Effects of school breaks on influenza-like illness incidence in a temperate Chinese region: an ecological study from 2008 to 2015,http://dx.doi.org/10.1136/bmjopen-2016-013159,PMC5353286,28264827,CC BY-NC,"OBJECTIVE: To assess the effects of winter/summer school breaks on occurrences of influenza-like illness (ILI). METHODS: We jointly analysed ILI surveillance data with the timing of school breaks in a temperate district in Beijing, China from 2008 to 2015. ILI incidence rate ratios (IRRs) of schoolchildren (5–14 and 15–24 years of age) to adults (25–59 and >60 years of age) were used to measure the age shift of ILI incidence before, during and after the 4-week winter/7-week summer breaks. Serfling-based Poisson regression model with adjustment for unmeasured confounders was built to further assess the effect of winter school breaks. RESULTS: ILI incidences were consistently lower during winter breaks than before winter breaks for all age groups. IRRs of younger schoolchildren aged 5–14 to adults were higher during winter school breaks than before breaks, while the opposite was true for the IRRs of older schoolchildren aged 15–24 to adults. Schoolchildren-to-adults IRRs during summer breaks were significantly lower than before or after school breaks (p<0.001). CONCLUSIONS: Both winter and summer breaks were associated with reductions of ILI incidences among schoolchildren and adults. Our study contributes additional evidence on the effects of school breaks on ILI incidence, suggesting school closure could be effective in controlling influenza transmission in developing countries.",2017 Mar 6,"['Chu, Yanhui', 'Wu, Zhenyu', 'Ji, Jiayi', 'Sun, Jingyi', 'Sun, Xiaoyu', 'Qin, Guoyou', 'Qin, Jingning', 'Xiao, Zheng', 'Ren, Jian', 'Qin, Di', 'Zheng, Xueying', 'Wang, Xi-Ling']",BMJ Open,,,True
9fe1fc9fce04dbef370abf2f658f6a4d34123c41,PMC,Effects of school breaks on influenza-like illness incidence in a temperate Chinese region: an ecological study from 2008 to 2015,http://dx.doi.org/10.1136/bmjopen-2016-013159,PMC5353286,28264827,CC BY-NC,"OBJECTIVE: To assess the effects of winter/summer school breaks on occurrences of influenza-like illness (ILI). METHODS: We jointly analysed ILI surveillance data with the timing of school breaks in a temperate district in Beijing, China from 2008 to 2015. ILI incidence rate ratios (IRRs) of schoolchildren (5–14 and 15–24 years of age) to adults (25–59 and >60 years of age) were used to measure the age shift of ILI incidence before, during and after the 4-week winter/7-week summer breaks. Serfling-based Poisson regression model with adjustment for unmeasured confounders was built to further assess the effect of winter school breaks. RESULTS: ILI incidences were consistently lower during winter breaks than before winter breaks for all age groups. IRRs of younger schoolchildren aged 5–14 to adults were higher during winter school breaks than before breaks, while the opposite was true for the IRRs of older schoolchildren aged 15–24 to adults. Schoolchildren-to-adults IRRs during summer breaks were significantly lower than before or after school breaks (p<0.001). CONCLUSIONS: Both winter and summer breaks were associated with reductions of ILI incidences among schoolchildren and adults. Our study contributes additional evidence on the effects of school breaks on ILI incidence, suggesting school closure could be effective in controlling influenza transmission in developing countries.",2017 Mar 6,"['Chu, Yanhui', 'Wu, Zhenyu', 'Ji, Jiayi', 'Sun, Jingyi', 'Sun, Xiaoyu', 'Qin, Guoyou', 'Qin, Jingning', 'Xiao, Zheng', 'Ren, Jian', 'Qin, Di', 'Zheng, Xueying', 'Wang, Xi-Ling']",BMJ Open,,,False
477645a85a65fb72adc9d17a09bf6d53ca3f24fd,PMC,Antimicrobial use Guidelines for Treatment of Respiratory Tract Disease in Dogs and Cats: Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases,http://dx.doi.org/10.1111/jvim.14627,PMC5354050,28185306,CC BY-NC,"Respiratory tract disease can be associated with primary or secondary bacterial infections in dogs and cats and is a common reason for use and potential misuse, improper use, and overuse of antimicrobials. There is a lack of comprehensive treatment guidelines such as those that are available for human medicine. Accordingly, the International Society for Companion Animal Infectious Diseases convened a Working Group of clinical microbiologists, pharmacologists, and internists to share experiences, examine scientific data, review clinical trials, and develop these guidelines to assist veterinarians in making antimicrobial treatment choices for use in the management of bacterial respiratory diseases in dogs and cats.",2017 Feb 10 Mar-Apr,"['Lappin, M.R.', 'Blondeau, J.', 'Boothe, D.', 'Breitschwerdt, E.B.', 'Guardabassi, L.', 'Lloyd, D.H.', 'Papich, M.G.', 'Rankin, S.C.', 'Sykes, J.E.', 'Turnidge, J.', 'Weese, J.S.']",J Vet Intern Med,,,True
7018967c7ebc76e4c6d3decf7e836957ff427602,PMC,Correlation of central venous pressure with venous blood gas analysis parameters; a diagnostic study,http://dx.doi.org/10.1016/j.tjem.2016.09.006,PMC5357094,28345066,CC BY-NC-ND,"OBJECTIVE: This study was conducted to assess the correlation between central venous pressure (CVP) and venous blood gas (VBG) analysis parameters, to facilitate management of severe sepsis and septic shock in emergency department. MATERIAL AND METHODS: This diagnostic study was conducted from January 2014 until June 2015 in three major educational medical centers, Tehran, Iran. For patients selected with diagnosis of septic shock, peripheral blood sample was taken for testing the VBG parameters and the anion gap (AG) was calculated. All the mentioned parameters were measured again after infusion of 500 cc of normal saline 0.9% in about 1 h. RESULTS: Totally, 93 patients with septic shock were enrolled, 63 male and 30 female. The mean age was 72.53 ± 13.03 and the mean Shock Index (SI) before fluid therapy was 0.79 ± 0.30. AG and pH showed significant negative correlations with CVP, While HCO3 showed a significant positive correlation with CVP. These relations can be affected by the treatment modalities used in shock management such as fluid therapy, mechanical ventilation and vasopressor treatment. CONCLUSION: It is likely that there is a significant statistical correlation between VBG parameters and AG with CVP, but further research is needed before implementation of the results of this study.",2016 Nov 20,"['Rahim-Taleghani, Sima', 'Fatemi, Alireza', 'Alavi Moghaddam, Mostafa', 'Shojaee, Majid', 'Abushouk, Abdelrahman Ibrahim', 'Forouzanfar, Mohammad Mehdi', 'Baratloo, Alireza']",Turk J Emerg Med,,,False
bc7219efb063d1c0aa002e536f9503f999fbcb42,PMC,Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection,http://dx.doi.org/10.1016/j.ebiom.2017.02.015,PMC5360578,28238698,CC BY-NC-ND,"Infection of respiratory mucosa with viral pathogens triggers complex immunologic events in the affected host. We sought to characterize this response through proteomic analysis of nasopharyngeal lavage in human subjects experimentally challenged with influenza A/H3N2 or human rhinovirus, and to develop targeted assays measuring peptides involved in this host response allowing classification of acute respiratory virus infection. Unbiased proteomic discovery analysis identified 3285 peptides corresponding to 438 unique proteins, and revealed that infection with H3N2 induces significant alterations in protein expression. These include proteins involved in acute inflammatory response, innate immune response, and the complement cascade. These data provide insights into the nature of the biological response to viral infection of the upper respiratory tract, and the proteins that are dysregulated by viral infection form the basis of signature that accurately classifies the infected state. Verification of this signature using targeted mass spectrometry in independent cohorts of subjects challenged with influenza or rhinovirus demonstrates that it performs with high accuracy (0.8623 AUROC, 75% TPR, 97.46% TNR). With further development as a clinical diagnostic, this signature may have utility in rapid screening for emerging infections, avoidance of inappropriate antibacterial therapy, and more rapid implementation of appropriate therapeutic and public health strategies.",2017 Feb 21,"['Burke, Thomas W.', 'Henao, Ricardo', 'Soderblom, Erik', 'Tsalik, Ephraim L.', 'Thompson, J. Will', 'McClain, Micah T.', 'Nichols, Marshall', 'Nicholson, Bradly P.', 'Veldman, Timothy', 'Lucas, Joseph E.', 'Moseley, M. Arthur', 'Turner, Ronald B.', 'Lambkin-Williams, Robert', 'Hero, Alfred O.', 'Woods, Christopher W.', 'Ginsburg, Geoffrey S.']",EBioMedicine,,,False
366d302151fd854813f4519551c7d8c5381c4fd7,PMC,Bartonella henselae as a cause of acute-onset febrile illness in cats,http://dx.doi.org/10.1177/2055116915600454,PMC5362002,28491382,CC BY-NC,"CASE SERIES SUMMARY: At different time points spanning 6 months, three adopted feral flea-infested cats, residing in the household of a veterinary technician, became acutely anorexic, lethargic and febrile. Enrichment blood culture/PCR using Bartonella alpha Proteobacteria growth medium (BAPGM) confirmed initial infection with the same Bartonella henselae genotype in all three cases. With the exception of anemia and neutropenia, complete blood counts, serum biochemical profiles and urinalysis results were within reference intervals. Also, tests for feline leukemia virus, feline immunodeficiency virus, Toxoplasma gondii and feline coronavirus antibodies were negative. Serial daily temperature monitoring in one case confirmed a cyclic, relapsing febrile temperature pattern during 1 month, with resolution during and after treatment with azithromycin. Bartonella henselae Western immunoblot (WB) results did not consistently correlate with BAPGM enrichment blood culture/PCR results or B henselae indirect fluorescent antibody (IFA) titers, and WB titration results were not informative for establishing antibiotic treatment failure. During the respective follow-up periods, no illnesses or additional febrile episodes were reported, despite repeat documentation of B henselae bacteremia in two cats available for follow-up (one with the same genotype and the other with a different B henselae genotype); one cat was, unfortunately, killed by dogs before follow-up testing. RELEVANCE AND NOVEL INFORMATION: We conclude that microbiological diagnosis and treatment of B henselae infection in cats can be challenging, that antibody titration results and resolution of clinical abnormalities may not correlate with a therapeutic cure, and that fever and potentially neutropenia should be differential diagnostic considerations for young cats with suspected bartonellosis.",2015 Sep 3,"['Breitschwerdt, Edward B', 'Broadhurst, Jack J', 'Cherry, Natalie A']",JFMS Open Rep,,,True
b3707acee35230b2cb6c548837f7f6ca94a26f6b,PMC,Probable primary polydipsia in a domestic shorthair cat,http://dx.doi.org/10.1177/2055116915615370,PMC5362011,28491395,CC BY-NC,"CASE SUMMARY: A 10-month-old neutered male domestic shorthair cat presented with a 4 month history of polyuria and polydipsia. After a thorough diagnostic work-up the only abnormal findings were hyposthenuria and an elevated random plasma osmolality level. Trial therapy with the oral and ophthalmic forms of desmopressin failed to concentrate urine. A modified water deprivation test confirmed the ability to concentrate urine above a urine specific gravity (USG) of 1.035. After transitioning the cat to a higher sodium diet and instituting several enrichment changes to the cat’s environment, average water consumption and urine output levels decreased to almost normal levels and USG increased from 1.006 to 1.022. These findings provide strong evidence that primary polydipsia was the underlying etiology of the cat’s condition. RELEVANCE AND NOVEL INFORMATION: This case report exemplifies the challenges faced when a cat presents for polyuria and polydipsia without an obvious cause identified on routine diagnostics. To our knowledge, this is the first report of primary polydipsia in a cat.",2015 Dec 1,"['Long, Charles Tyler', 'Williams, Morika', 'Savage, Mason', 'Fogle, Jonathan', 'Meeker, Rick', 'Hudson, Lola']",JFMS Open Rep,,,True
33842ff07428db8111b5c1aa9421d7272f523602,PMC,A survey of feline leukaemia virus antigenaemia among cats in eastern Austria: a retrospective analysis of serum samples routinely tested between 1996 and 2011,http://dx.doi.org/10.1177/2055116915598336,PMC5362014,28491380,CC BY-NC,"OBJECTIVES: The aim of this retrospective analysis was to determine the seroprevalence of feline leukaemia virus (FeLV) antigenaemia among owned cats in Vienna and the surrounding area. METHODS: Samples were tested between 1996 and 2011 by the Department of Clinical Virology at the University of Veterinary Medicine, Vienna, Austria. All samples were sent to the university as part of routine diagnostic procedures, either to determine infection in clinically symptomatic individuals or to rule out infection prior to vaccination. To allow for statistical comparison, samples analysed between 2008 and 2011 were pooled into one population (n = 444) and evaluated against samples tested in 1996 (n = 840). Furthermore, analyses of subgroups were undertaken to determine the effect of sex and age on the prevalence of FeLV antigenaemia. RESULTS: With respect to the samples tested at the University of Veterinary Medicine in Vienna, it was determined that the level of FeLV antigenaemia in eastern Austria between 1996 and 2011 was 5.6%. The proportion of FeLV antigenaemic cats was highly variable and has not fallen significantly over this period, despite advances in vaccination, and the education of pet owners and animal welfare charities. CONCLUSIONS AND RELEVANCE: This study confirms the importance of continued and regular vaccination against FeLV among Austrian cats, particularly those allowed access to the outdoors. Within the remit of this retrospective study, it was not possible to follow-up results of repeat testing or of other assays (PCR) of individual cats. As a result of this, no conclusions can be drawn as to the possibility of transient antigenaemic cats or false-positive enzyme-linked immunosorbent assay results.",2015 Jul 29,"['Firth, Clair L', 'Möstl, Karin']",JFMS Open Rep,,,True
b2f0e12f8f1cb35be12a8b139547c7d570aedaf0,PMC,Primary bronchial carcinoma associated with bone marrow metastasis and paraneoplastic monoclonal gammopathy in a cat,http://dx.doi.org/10.1177/2055116916668200,PMC5362843,28491436,CC BY-NC,"CASE SUMMARY: Herein we describe an unusual metastatic pattern and paraneoplastic manifestation of a bronchial carcinoma in a cat. An 8 year-old cat presented with a diminished appetite, dysphagia, weight loss, lethargy and coughing. Thoracic radiographs revealed a lung mass. Bronchial carcinoma was diagnosed on the basis of histology and was associated with a lymphoplasmocytic infiltration of the fibrovascular stroma. Biochemistry showed hyperproteinaemia. Serum protein electrophoresis showed a narrow spike in the gamma region. Bone marrow cytology revealed an infiltrate with numerous clustered epithelial cells. The cat was euthanased 2 months later because of anorexia and poor general condition. RELEVANCE AND NOVEL INFORMATION: To the best of our knowledge, this is the first clinical description of primary bronchial carcinoma associated with bone marrow metastases and paraneoplastic monoclonal gammopathy in a cat.",2016 Sep 30,"['Cervone, Mario', 'Beurlet, Stéphanie']",JFMS Open Rep,,,True
357af8bb837fb3521423284fa624316d0965bfa3,PMC,Successful treatment of feline leishmaniosis using a combination of allopurinol and N-methyl-glucamine antimoniate,http://dx.doi.org/10.1177/2055116916630002,PMC5362848,28491411,CC BY-NC,"CASE SUMMARY: This work describes the diagnosis and successful treatment of a 2-year-old domestic cat infected with Leishmania species and presenting fever, and ulcerative and nodular skin lesions after being treated for pyodermatitis for 1 year without clinical improvement. After anamnesis the cat was submitted to a complete clinical examination. Blood was collected for determination of haematological and biochemical parameters, detection of feline leukaemia virus (FeLV), feline immunodeficiency virus (FIV), feline coronavirus (FCoV) and Leishmania amastigotes. Fine-needle aspiration puncture from the skin nodules was also performed. After definitive diagnosis the animal was treated and followed up over a 2 year period. The animal tested negative for FIV-specific antibodies, FeLV antigen and feline coronavirus RNA. Leishmania amastigotes in the skin nodules were confirmed by cytology and molecular diagnosis. Treatment was initiated with allopurinol, resulting in a slight clinical improvement. Thus, N-methyl-glucamine antimoniate was added and administered for 30 days, with complete closure of the ulcerative lesions in the hindlimbs requiring a surgical approach. Close monitoring of the patient in the following 24 months indicated that combined therapy was safe and clinical cure was achieved without further relapses or side effects. RELEVANCE AND NOVEL INFORMATION: Considering the increasing number of feline leishmaniosis cases and the inconsistent results of most therapeutic protocols described in the literature, the use of new approaches, especially in refractory cases, is essential. Although the use of allopurinol and N-methyl-glucamine antimoniate is off-label in cats, in this case the combination treatment was followed by an extensive analytical monitoring, supporting their safety and effectiveness.",2016 Feb 10,"['Basso, Maria Alexandra', 'Marques, Cátia', 'Santos, Marcos', 'Duarte, Ana', 'Pissarra, Hugo', 'Carreira, L Miguel', 'Gomes, Lídia', 'Valério-Bolas, Ana', 'Tavares, Luís', 'Santos-Gomes, Gabriela', 'Pereira da Fonseca, Isabel']",JFMS Open Rep,,,True
19d6f61adafc680a5de0188f77c11bb9157be3e1,PMC,Neglected dorsolateral dislocation of the first metatarsophalangeal joint: A case report,http://dx.doi.org/10.1016/j.ijscr.2017.02.031,PMC5369860,28347926,CC BY-NC-ND,"INTRODUCTION: Although the first metatarsophalangeal (MTP) joint is frequently injured, Complete dislocation of the first MTP joint represents a relatively rare traumatic injury. PRESENTATION OF CASE: A 46-year-old gentleman presented with a traumatic first MTP joint dislocation resulting from an automobile accident. Due to coronavirus outbreak in the hospital at that time, patient was referred to another hospital. Six months later, reduction was achieved surgically and fixation of the MTP with K-wires was done. DISCUSSION: Only few case reports have described the injury, and the ideal treatment along with the long-term result of the injury has yet to be further studied because reports are rare in this regard. CONCLUSION: Functional range of motion may result even after 6 months of delayed treatment with ORIF and osteopenia may result.",2017 Feb 21,"['Al-Mohrej, Omar A.', 'AlOmair, Abdulrahman A.', 'Alfehaid, Yara A.', 'Alsumali, Abubaker A.', 'Al-Kenani, Nader S.']",Int J Surg Case Rep,,,False
671e9e8a89727d0b94d1798c56f5120c63c83617,PMC,Prevalence and genetic characteristics of Saffold cardiovirus in China from 2009 to 2012,http://dx.doi.org/10.1038/srep07704,PMC5378990,25572936,CC BY-NC-ND,"The epidemiology and clinical features of the Saffold cardiovirus (SAFV) remain ambiguous. The present study was designed to systematically and intensively investigate the epidemiological features of SAFV in pediatric patients in China. Three cohorts of pediatric patients were recruited from 2009 to 2012. Cohort 1 comprised patients with acute respiratory tract infections. Cohort 2 comprised patients with diarrhea. Cohort 3 comprised hand, foot, and mouth disease (HFMD) patients. A total of 115 patients (1.6%) among 6052 (17/1647, 12/2013, and 86/2392 in cohorts 1, 2, and 3, respectively) were SAFV-positive. The samples from 82 SAFV-positive patients were successfully sequenced, and four genotypes were identified: 8 SAFV-1, 41 SAFV-2, 29 SAFV-3, and 4 SAFV-6. A significantly higher detection rate was found in the HFMD patients than in other two cohorts (both P <0.001). A higher frequency of severe clinical outcome and nervous system manifestation were also observed in the SAFV-positive HFMD patients. Additionally, 6 (3.5%) cerebrospinal fluid and 7 (2.2%) serum samples from the HFMD-associated encephalitis patients were SAFV-positive. Based on the VP1 sequences, all four genotypes displayed distinct geographical clustering. SAFV infection might be associated with a wide clinical spectrum and contribute to HFMD.",2015 Jan 9,"['Zhang, Xiao-Ai', 'Lu, Qing-Bin', 'Wo, Ying', 'Zhao, Jin', 'Huang, Dou-Dou', 'Guo, Chen-Tao', 'Xu, Hong-Mei', 'Liu, En-Mei', 'Liu, Wei', 'Cao, Wu-Chun']",Sci Rep,,,True
b73380f2ef930b1667b665389463cf944db47370,PMC,Infrared thermal imaging in connective tissue diseases,http://dx.doi.org/10.5114/reum.2017.66686,PMC5380771,28386141,CC BY-NC-SA,"Infrared thermal imaging (IRT) is a non-invasive, non-contact technique which allows one to measure and visualize infrared radiation. In medicine, thermal imaging has been used for more than 50 years in various clinical settings, including Raynaud’s phenomenon and systemic sclerosis. Imaging and quantification of surface body temperature provides an indirect measure of the microcirculation’s overall performance. As such, IRT is capable of confirming the diagnosis of Raynaud’s phenomenon, and, with additional cold or heat challenge, of differentiating between the primary and secondary condition. In systemic sclerosis IRT has a potential role in assessing disease activity and monitoring treatment response. Despite certain limitations, thermal imaging can find a place in clinical practice, and with the introduction of small, low-cost infrared cameras, possibly become a part of routine rheumatological evaluation.",2017 Mar 22,"Chojnowski, Marek",Reumatologia,,,True
7f070cac1f9fd46107d2a521e65b385e87efea85,PMC,Progress of small molecular inhibitors in the development of anti-influenza virus agents,http://dx.doi.org/10.7150/thno.17071,PMC5381247,28382157,CC BY-NC,"The influenza pandemic is a major threat to human health, and highly aggressive strains such as H1N1, H5N1 and H7N9 have emphasized the need for therapeutic strategies to combat these pathogens. Influenza anti-viral agents, especially active small molecular inhibitors play important roles in controlling pandemics while vaccines are developed. Currently, only a few drugs, which function as influenza neuraminidase (NA) inhibitors and M2 ion channel protein inhibitors, are approved in clinical. However, the acquired resistance against current anti-influenza drugs and the emerging mutations of influenza virus itself remain the major challenging unmet medical needs for influenza treatment. It is highly desirable to identify novel anti-influenza agents. This paper reviews the progress of small molecular inhibitors act as antiviral agents, which include hemagglutinin (HA) inhibitors, RNA-dependent RNA polymerase (RdRp) inhibitors, NA inhibitors and M2 ion channel protein inhibitors etc. Moreover, we also summarize new, recently reported potential targets and discuss strategies for the development of new anti-influenza virus drugs.",2017 Feb 8,"['Wu, Xiaoai', 'Wu, Xiuli', 'Sun, Qizheng', 'Zhang, Chunhui', 'Yang, Shengyong', 'Li, Lin', 'Jia, Zhiyun']",Theranostics,,,True
97b7ac41d4b2537b9b38666adc27439a808234a5,PMC,Development of a one-run real-time PCR detection system for pathogens associated with bovine respiratory disease complex,http://dx.doi.org/10.1292/jvms.16-0489,PMC5383171,28070089,CC BY-NC-ND,"Bovine respiratory disease complex (BRDC) is frequently found in cattle worldwide. The etiology of BRDC is complicated by infections with multiple pathogens, making identification of the causal pathogen difficult. Here, we developed a detection system by applying TaqMan real-time PCR (Dembo respiratory-PCR) to screen a broad range of microbes associated with BRDC in a single run. We selected 16 bovine respiratory pathogens (bovine viral diarrhea virus, bovine coronavirus, bovine parainfluenza virus 3, bovine respiratory syncytial virus, influenza D virus, bovine rhinitis A virus, bovine rhinitis B virus, bovine herpesvirus 1, bovine adenovirus 3, bovine adenovirus 7, Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Trueperella pyogenes, Mycoplasma bovis and Ureaplasma diversum) as detection targets and designed novel specific primer-probe sets for nine of them. The assay performance was assessed using standard curves from synthesized DNA. In addition, the sensitivity of the assay was evaluated by spiking solutions extracted from nasal swabs that were negative by Dembo respiratory-PCR for nucleic acids of pathogens or synthesized DNA. All primer-probe sets showed high sensitivity. In this study, a total of 40 nasal swab samples from cattle on six farms were tested by Dembo respiratory-PCR. Dembo respiratory-PCR can be applied as a screening system with wide detection targets.",2017 Mar 8,"['KISHIMOTO, Mai', 'TSUCHIAKA, Shinobu', 'RAHPAYA, Sayed Samim', 'HASEBE, Ayako', 'OTSU, Keiko', 'SUGIMURA, Satoshi', 'KOBAYASHI, Suguru', 'KOMATSU, Natsumi', 'NAGAI, Makoto', 'OMATSU, Tsutomu', 'NAOI, Yuki', 'SANO, Kaori', 'OKAZAKI-TERASHIMA, Sachiko', 'OBA, Mami', 'KATAYAMA, Yukie', 'SATO, Reiichiro', 'ASAI, Tetsuo', 'MIZUTANI, Tetsuya']",J Vet Med Sci,,,True
ee4aeb7f3b9d1f6fa0db2c6d1c348c41c94a7974,PMC,Development of a one-run real-time PCR detection system for pathogens associated with bovine respiratory disease complex,http://dx.doi.org/10.1292/jvms.16-0489,PMC5383171,28070089,CC BY-NC-ND,"Bovine respiratory disease complex (BRDC) is frequently found in cattle worldwide. The etiology of BRDC is complicated by infections with multiple pathogens, making identification of the causal pathogen difficult. Here, we developed a detection system by applying TaqMan real-time PCR (Dembo respiratory-PCR) to screen a broad range of microbes associated with BRDC in a single run. We selected 16 bovine respiratory pathogens (bovine viral diarrhea virus, bovine coronavirus, bovine parainfluenza virus 3, bovine respiratory syncytial virus, influenza D virus, bovine rhinitis A virus, bovine rhinitis B virus, bovine herpesvirus 1, bovine adenovirus 3, bovine adenovirus 7, Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Trueperella pyogenes, Mycoplasma bovis and Ureaplasma diversum) as detection targets and designed novel specific primer-probe sets for nine of them. The assay performance was assessed using standard curves from synthesized DNA. In addition, the sensitivity of the assay was evaluated by spiking solutions extracted from nasal swabs that were negative by Dembo respiratory-PCR for nucleic acids of pathogens or synthesized DNA. All primer-probe sets showed high sensitivity. In this study, a total of 40 nasal swab samples from cattle on six farms were tested by Dembo respiratory-PCR. Dembo respiratory-PCR can be applied as a screening system with wide detection targets.",2017 Mar 8,"['KISHIMOTO, Mai', 'TSUCHIAKA, Shinobu', 'RAHPAYA, Sayed Samim', 'HASEBE, Ayako', 'OTSU, Keiko', 'SUGIMURA, Satoshi', 'KOBAYASHI, Suguru', 'KOMATSU, Natsumi', 'NAGAI, Makoto', 'OMATSU, Tsutomu', 'NAOI, Yuki', 'SANO, Kaori', 'OKAZAKI-TERASHIMA, Sachiko', 'OBA, Mami', 'KATAYAMA, Yukie', 'SATO, Reiichiro', 'ASAI, Tetsuo', 'MIZUTANI, Tetsuya']",J Vet Med Sci,,,False
49c8f45d390502809816b630ee23375427ea0fb6,PMC,Intestinal gastrointestinal stromal tumor in a cat,http://dx.doi.org/10.1292/jvms.16-0605,PMC5383177,28163271,CC BY-NC-ND,"A 12-year-old, 3.6-kg, spayed female domestic shorthaired cat had a 2-month history of anorexia and weight loss. Abdominal ultrasonography and computed tomography revealed an exophytic mass originating from the jejunum with very poor central and poor peripheral contrast enhancement. On day 14, surgical resection of the jejunum and mass with 5-cm margins and an end-to-end anastomosis were performed. Histopathological examination revealed the mass was a transmural, invasive cancer showing exophytic growth and originating from the small intestinal muscle layer. Immunohistochemical analysis of tumor cells revealed diffuse positivity for KIT protein and negativity for desmin and S-100. The mass was diagnosed as a gastrointestinal stromal tumor (GIST). Ultrasonographic findings indicated the tumor probably metastasized to the liver and omentum, as seen in humans and dogs. The owner rejected further treatment at the last visit on day 192. To our knowledge, this is the first report of intestinal tumor and metastasis in feline GIST and its imaging features.",2017 Mar 4,"['SUWA, Akihisa', 'SHIMODA, Tetsuya']",J Vet Med Sci,,,True
584690fd413d25e55ee5599071bd23b1be00add0,PMC,Clinical and Epidemiologic Characteristics of Spreaders of Middle East Respiratory Syndrome Coronavirus during the 2015 Outbreak in Korea,http://dx.doi.org/10.3346/jkms.2017.32.5.744,PMC5383605,28378546,CC BY-NC,"Nosocomial transmission is an important characteristic of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. Risk factors for transmission of MERS-CoV in healthcare settings are not well defined. During the Korean outbreak in 2015, 186 patients had laboratory-confirmed MERS-CoV infection. Those suspected as a source of viral transmission were categorized into the spreader groups (super-spreader [n = 5] and usual-spreader [n = 10]) and compared to the non-spreader group (n = 171). Body temperature of ≥ 38.5°C (adjusted odds ratio [aOR], 5.54; 95% confidence interval [CI], 1.38–22.30; P = 0.016), pulmonary infiltration of ≥ 3 lung zones (aOR, 7.33; 95% CI, 1.93–27.79; P = 0.003), and a more nonisolated in-hospital days (aOR, 1.32 per 1 day; 95% CI, 1.09–1.60; P = 0.004) were significant risk factors in the spreader group. There was no different clinical factor between super-spreaders and usual-spreaders. Nonisolated in-hospital days was the only factor which tended to be higher in super-spreaders than usual-spreaders (Mean, 6.6 vs. 2.9 days; P = 0.061). Early active quarantine might help reducing the size of an outbreak.",2017 May 17,"['Kang, Chang Kyung', 'Song, Kyoung-Ho', 'Choe, Pyoeng Gyun', 'Park, Wan Beom', 'Bang, Ji Hwan', 'Kim, Eu Suk', 'Park, Sang Won', 'Kim, Hong Bin', 'Kim, Nam Joong', 'Cho, Sung-il', 'Lee, Jong-koo', 'Oh, Myoung-don']",J Korean Med Sci,,,True
7c5b49af648a479b8a1e7fcc3dc88751b014bf08,PMC,Clinical and Epidemiologic Characteristics of Spreaders of Middle East Respiratory Syndrome Coronavirus during the 2015 Outbreak in Korea,http://dx.doi.org/10.3346/jkms.2017.32.5.744,PMC5383605,28378546,CC BY-NC,"Nosocomial transmission is an important characteristic of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. Risk factors for transmission of MERS-CoV in healthcare settings are not well defined. During the Korean outbreak in 2015, 186 patients had laboratory-confirmed MERS-CoV infection. Those suspected as a source of viral transmission were categorized into the spreader groups (super-spreader [n = 5] and usual-spreader [n = 10]) and compared to the non-spreader group (n = 171). Body temperature of ≥ 38.5°C (adjusted odds ratio [aOR], 5.54; 95% confidence interval [CI], 1.38–22.30; P = 0.016), pulmonary infiltration of ≥ 3 lung zones (aOR, 7.33; 95% CI, 1.93–27.79; P = 0.003), and a more nonisolated in-hospital days (aOR, 1.32 per 1 day; 95% CI, 1.09–1.60; P = 0.004) were significant risk factors in the spreader group. There was no different clinical factor between super-spreaders and usual-spreaders. Nonisolated in-hospital days was the only factor which tended to be higher in super-spreaders than usual-spreaders (Mean, 6.6 vs. 2.9 days; P = 0.061). Early active quarantine might help reducing the size of an outbreak.",2017 May 17,"['Kang, Chang Kyung', 'Song, Kyoung-Ho', 'Choe, Pyoeng Gyun', 'Park, Wan Beom', 'Bang, Ji Hwan', 'Kim, Eu Suk', 'Park, Sang Won', 'Kim, Hong Bin', 'Kim, Nam Joong', 'Cho, Sung-il', 'Lee, Jong-koo', 'Oh, Myoung-don']",J Korean Med Sci,,,False
b74223f9924da50ce0ff5a4bd3175f64e642059b,PMC,Clinical and Epidemiologic Characteristics of Spreaders of Middle East Respiratory Syndrome Coronavirus during the 2015 Outbreak in Korea,http://dx.doi.org/10.3346/jkms.2017.32.5.744,PMC5383605,28378546,CC BY-NC,"Nosocomial transmission is an important characteristic of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. Risk factors for transmission of MERS-CoV in healthcare settings are not well defined. During the Korean outbreak in 2015, 186 patients had laboratory-confirmed MERS-CoV infection. Those suspected as a source of viral transmission were categorized into the spreader groups (super-spreader [n = 5] and usual-spreader [n = 10]) and compared to the non-spreader group (n = 171). Body temperature of ≥ 38.5°C (adjusted odds ratio [aOR], 5.54; 95% confidence interval [CI], 1.38–22.30; P = 0.016), pulmonary infiltration of ≥ 3 lung zones (aOR, 7.33; 95% CI, 1.93–27.79; P = 0.003), and a more nonisolated in-hospital days (aOR, 1.32 per 1 day; 95% CI, 1.09–1.60; P = 0.004) were significant risk factors in the spreader group. There was no different clinical factor between super-spreaders and usual-spreaders. Nonisolated in-hospital days was the only factor which tended to be higher in super-spreaders than usual-spreaders (Mean, 6.6 vs. 2.9 days; P = 0.061). Early active quarantine might help reducing the size of an outbreak.",2017 May 17,"['Kang, Chang Kyung', 'Song, Kyoung-Ho', 'Choe, Pyoeng Gyun', 'Park, Wan Beom', 'Bang, Ji Hwan', 'Kim, Eu Suk', 'Park, Sang Won', 'Kim, Hong Bin', 'Kim, Nam Joong', 'Cho, Sung-il', 'Lee, Jong-koo', 'Oh, Myoung-don']",J Korean Med Sci,,,False
7220814e1372389732da905379844750cd868045,PMC,Clinical and Epidemiologic Characteristics of Spreaders of Middle East Respiratory Syndrome Coronavirus during the 2015 Outbreak in Korea,http://dx.doi.org/10.3346/jkms.2017.32.5.744,PMC5383605,28378546,CC BY-NC,"Nosocomial transmission is an important characteristic of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. Risk factors for transmission of MERS-CoV in healthcare settings are not well defined. During the Korean outbreak in 2015, 186 patients had laboratory-confirmed MERS-CoV infection. Those suspected as a source of viral transmission were categorized into the spreader groups (super-spreader [n = 5] and usual-spreader [n = 10]) and compared to the non-spreader group (n = 171). Body temperature of ≥ 38.5°C (adjusted odds ratio [aOR], 5.54; 95% confidence interval [CI], 1.38–22.30; P = 0.016), pulmonary infiltration of ≥ 3 lung zones (aOR, 7.33; 95% CI, 1.93–27.79; P = 0.003), and a more nonisolated in-hospital days (aOR, 1.32 per 1 day; 95% CI, 1.09–1.60; P = 0.004) were significant risk factors in the spreader group. There was no different clinical factor between super-spreaders and usual-spreaders. Nonisolated in-hospital days was the only factor which tended to be higher in super-spreaders than usual-spreaders (Mean, 6.6 vs. 2.9 days; P = 0.061). Early active quarantine might help reducing the size of an outbreak.",2017 May 17,"['Kang, Chang Kyung', 'Song, Kyoung-Ho', 'Choe, Pyoeng Gyun', 'Park, Wan Beom', 'Bang, Ji Hwan', 'Kim, Eu Suk', 'Park, Sang Won', 'Kim, Hong Bin', 'Kim, Nam Joong', 'Cho, Sung-il', 'Lee, Jong-koo', 'Oh, Myoung-don']",J Korean Med Sci,,,False
e96ca569ef9ee23093b5dad3ee0c55ed13a37a6e,PMC,Clinical and Epidemiologic Characteristics of Spreaders of Middle East Respiratory Syndrome Coronavirus during the 2015 Outbreak in Korea,http://dx.doi.org/10.3346/jkms.2017.32.5.744,PMC5383605,28378546,CC BY-NC,"Nosocomial transmission is an important characteristic of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. Risk factors for transmission of MERS-CoV in healthcare settings are not well defined. During the Korean outbreak in 2015, 186 patients had laboratory-confirmed MERS-CoV infection. Those suspected as a source of viral transmission were categorized into the spreader groups (super-spreader [n = 5] and usual-spreader [n = 10]) and compared to the non-spreader group (n = 171). Body temperature of ≥ 38.5°C (adjusted odds ratio [aOR], 5.54; 95% confidence interval [CI], 1.38–22.30; P = 0.016), pulmonary infiltration of ≥ 3 lung zones (aOR, 7.33; 95% CI, 1.93–27.79; P = 0.003), and a more nonisolated in-hospital days (aOR, 1.32 per 1 day; 95% CI, 1.09–1.60; P = 0.004) were significant risk factors in the spreader group. There was no different clinical factor between super-spreaders and usual-spreaders. Nonisolated in-hospital days was the only factor which tended to be higher in super-spreaders than usual-spreaders (Mean, 6.6 vs. 2.9 days; P = 0.061). Early active quarantine might help reducing the size of an outbreak.",2017 May 17,"['Kang, Chang Kyung', 'Song, Kyoung-Ho', 'Choe, Pyoeng Gyun', 'Park, Wan Beom', 'Bang, Ji Hwan', 'Kim, Eu Suk', 'Park, Sang Won', 'Kim, Hong Bin', 'Kim, Nam Joong', 'Cho, Sung-il', 'Lee, Jong-koo', 'Oh, Myoung-don']",J Korean Med Sci,,,False
d0d2d06d929e87062c621fcc53aba7712918ca05,PMC,Clinical and Epidemiologic Characteristics of Spreaders of Middle East Respiratory Syndrome Coronavirus during the 2015 Outbreak in Korea,http://dx.doi.org/10.3346/jkms.2017.32.5.744,PMC5383605,28378546,CC BY-NC,"Nosocomial transmission is an important characteristic of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. Risk factors for transmission of MERS-CoV in healthcare settings are not well defined. During the Korean outbreak in 2015, 186 patients had laboratory-confirmed MERS-CoV infection. Those suspected as a source of viral transmission were categorized into the spreader groups (super-spreader [n = 5] and usual-spreader [n = 10]) and compared to the non-spreader group (n = 171). Body temperature of ≥ 38.5°C (adjusted odds ratio [aOR], 5.54; 95% confidence interval [CI], 1.38–22.30; P = 0.016), pulmonary infiltration of ≥ 3 lung zones (aOR, 7.33; 95% CI, 1.93–27.79; P = 0.003), and a more nonisolated in-hospital days (aOR, 1.32 per 1 day; 95% CI, 1.09–1.60; P = 0.004) were significant risk factors in the spreader group. There was no different clinical factor between super-spreaders and usual-spreaders. Nonisolated in-hospital days was the only factor which tended to be higher in super-spreaders than usual-spreaders (Mean, 6.6 vs. 2.9 days; P = 0.061). Early active quarantine might help reducing the size of an outbreak.",2017 May 17,"['Kang, Chang Kyung', 'Song, Kyoung-Ho', 'Choe, Pyoeng Gyun', 'Park, Wan Beom', 'Bang, Ji Hwan', 'Kim, Eu Suk', 'Park, Sang Won', 'Kim, Hong Bin', 'Kim, Nam Joong', 'Cho, Sung-il', 'Lee, Jong-koo', 'Oh, Myoung-don']",J Korean Med Sci,,,False
cccc79beb9b80834fd6302ddec0eb65633ce3f95,PMC,Spinal anesthesia after intraoperative cardiac arrest during general anesthesia in an infant,http://dx.doi.org/10.2147/LRA.S123157,PMC5386604,28435322,CC BY-NC,"Although generally safe and effective, severe perioperative complications, including cardiac arrest, may occur during general anesthesia in infants. With the emergence of evidence that specific anesthetic agents may affect future neurocognitive outcomes, there has been an increased focus on alternatives to general anesthesia, including spinal anesthesia. We present a case of cardiac arrest during general anesthesia in an infant who required urologic surgery. During the subsequent anesthetic care, spinal anesthesia was offered as an alternative to general anesthesia. The risks of severe perioperative complications during general anesthesia are reviewed, etiologic factors for such events are presented, and the use of spinal anesthesia as an alternative to general anesthesia is discussed.",2017 Mar 31,"['Whitaker, Emmett E', 'Miler, Veronica', 'Bryant, Jason', 'Proicou, Stephanie', 'Jayanthi, Rama', 'Tobias, Joseph D']",Local Reg Anesth,,,True
674e4b0b5ce420b596a783bf0d9d7fccc5a76403,PMC,Evaluation of disaster preparedness for mass casualty incidents in private hospitals in Central Saudi Arabia,http://dx.doi.org/10.15537/smj.2017.3.17483,PMC5387908,28251227,CC BY-NC-SA,"OBJECTIVES: To identify and describe the hospital disaster preparedness (HDP) in major private hospitals in Riyadh, Saudi Arabia. METHODS: This is an observational cross-sectional survey study performed in Riyadh city, Saudi Arabia between December 2015 and April 2016. Thirteen major private hospitals in Riyadh with more than 100 beds capacity were included in this investigation. RESULTS: The 13 hospitals had HDP plan and reported to have an HDP committee. In 12 (92.3%) hospitals, the HDP covered both internal and external disasters and HDP was available in every department of the hospital. There were agreements with other hospitals to accept patients during disasters in 9 facilities (69.2%) while 4 (30.8%) did not have such agreement. None of the hospitals conducted any unannounced exercises in previous year. CONCLUSION: Most of the weaknesses were apparent particularly in the education, training and monitoring of the hospital staff to the preparedness for disaster emergency occasion. Few hospitals had conducted an exercise with casualties, few had drilled evacuation of staff and patients in the last 12 months, and none had any unannounced exercise in the last year.",2017 Mar,"['Shalhoub, Abdullah A. Bin', 'Khan, Anas A.', 'Alaska, Yaser A.']",Saudi Med J,,,True
d5957419c56ec4aaf3fc7702330f84b0d5951cc1,PMC,Origin and Evolution of the Kiwifruit Canker Pandemic,http://dx.doi.org/10.1093/gbe/evx055,PMC5388287,28369338,CC BY-NC,"Recurring epidemics of kiwifruit (Actinidia spp.) bleeding canker disease are caused by Pseudomonas syringae pv. actinidiae (Psa). In order to strengthen understanding of population structure, phylogeography, and evolutionary dynamics, we isolated Pseudomonas from cultivated and wild kiwifruit across six provinces in China. Based on the analysis of 80 sequenced Psa genomes, we show that China is the origin of the pandemic lineage but that strain diversity in China is confined to just a single clade. In contrast, Korea and Japan harbor strains from multiple clades. Distinct independent transmission events marked introduction of the pandemic lineage into New Zealand, Chile, Europe, Korea, and Japan. Despite high similarity within the core genome and minimal impact of within-clade recombination, we observed extensive variation even within the single clade from which the global pandemic arose.",2017 Apr 1,"['McCann, Honour C.', 'Li, Li', 'Liu, Yifei', 'Li, Dawei', 'Pan, Hui', 'Zhong, Caihong', 'Rikkerink, Erik H.A.', 'Templeton, Matthew D.', 'Straub, Christina', 'Colombi, Elena', 'Rainey, Paul B.', 'Huang, Hongwen']",Genome Biol Evol,,,True
d949e3b7ef8b7cc48399d5ab806e0257218c6307,PMC,A high-throughput approach to profile RNA structure,http://dx.doi.org/10.1093/nar/gkw1094,PMC5389523,27899588,CC BY-NC,"Here we introduce the Computational Recognition of Secondary Structure (CROSS) method to calculate the structural profile of an RNA sequence (single- or double-stranded state) at single-nucleotide resolution and without sequence length restrictions. We trained CROSS using data from high-throughput experiments such as Selective 2΄-Hydroxyl Acylation analyzed by Primer Extension (SHAPE; Mouse and HIV transcriptomes) and Parallel Analysis of RNA Structure (PARS; Human and Yeast transcriptomes) as well as high-quality NMR/X-ray structures (PDB database). The algorithm uses primary structure information alone to predict experimental structural profiles with >80% accuracy, showing high performances on large RNAs such as Xist (17 900 nucleotides; Area Under the ROC Curve AUC of 0.75 on dimethyl sulfate (DMS) experiments). We integrated CROSS in thermodynamics-based methods to predict secondary structure and observed an increase in their predictive power by up to 30%.",2017 Mar 17,"['Delli\xa0Ponti, Riccardo', 'Marti, Stefanie', 'Armaos, Alexandros', 'Tartaglia, Gian\xa0Gaetano']",Nucleic Acids Res,,,True
02eb3dc5054c0dd2ce8faa06d6942484900d76c6,PMC,SIRT7-dependent deacetylation of CDK9 activates RNA polymerase II transcription,http://dx.doi.org/10.1093/nar/gkx053,PMC5389538,28426094,CC BY-NC,"SIRT7 is an NAD(+)-dependent protein deacetylase that regulates cell growth and proliferation. Previous studies have shown that SIRT7 is required for RNA polymerase I (Pol I) transcription and pre-rRNA processing. Here, we took a proteomic approach to identify novel molecular targets and characterize the role of SIRT7 in non-nucleolar processes. We show that SIRT7 interacts with numerous proteins involved in transcriptional regulation and RNA metabolism, the majority of interactions requiring ongoing transcription. In addition to its role in Pol I transcription, we found that SIRT7 also regulates transcription of snoRNAs and mRNAs. Mechanistically, SIRT7 promotes the release of P-TEFb from the inactive 7SK snRNP complex and deacetylates CDK9, a subunit of the elongation factor P-TEFb, which activates transcription by phosphorylating serine 2 within the C-terminal domain (CTD) of Pol II. SIRT7 counteracts GCN5-directed acetylation of lysine 48 within the catalytic domain of CDK9, deacetylation promoting CTD phosphorylation and transcription elongation.",2017 Mar 17,"['Blank, Maximilian F.', 'Chen, Sifan', 'Poetz, Fabian', 'Schnölzer, Martina', 'Voit, Renate', 'Grummt, Ingrid']",Nucleic Acids Res,,,True
98227f184bc6a0b098b4ae6387f97264aaf13654,PMC,EF-G catalyzed translocation dynamics in the presence of ribosomal frameshifting stimulatory signals,http://dx.doi.org/10.1093/nar/gkw1020,PMC5389563,27799473,CC BY-NC,"Programmed -1 ribosomal frameshifting (-1PRF) is tightly regulated by messenger RNA (mRNA) sequences and structures in expressing two or more proteins with precise ratios from a single mRNA. Using single-molecule fluorescence resonance energy transfer (smFRET) between (Cy5)EF-G and (Cy3)tRNA(Lys), we studied the translational elongation dynamics of -1PRF in the Escherichia coli dnaX gene, which contains three frameshifting signals: a slippery sequence (A AAA AAG), a Shine-Dalgarno (SD) sequence and a downstream hairpin. The frameshift promoting signals mostly impair the EF-G-catalyzed translocation step of the two tRNA(Lys) and the slippery codons from the A- and P- sites. The hairpin acts as a road block slowing the translocation rate. The upstream SD sequence together with the hairpin promotes dissociation of futile EF-G and thus causes multiple EF-G driven translocation attempts. A slippery sequence also helps dissociation of the EF-G by providing alternative base-pairing options. These results indicate that frameshifting takes place during the repetitive ribosomal conformational changes associated with EF-G dissociation upon unsuccessful translocation attempts of the second slippage codon from the A- to the P- sites.",2017 Mar 17,"['Kim, Hee-Kyung', 'Tinoco, Ignacio']",Nucleic Acids Res,,,True
69b46ece4c58dd1b2f507cca14cf0da14bb58387,PMC,EF-G catalyzed translocation dynamics in the presence of ribosomal frameshifting stimulatory signals,http://dx.doi.org/10.1093/nar/gkw1020,PMC5389563,27799473,CC BY-NC,"Programmed -1 ribosomal frameshifting (-1PRF) is tightly regulated by messenger RNA (mRNA) sequences and structures in expressing two or more proteins with precise ratios from a single mRNA. Using single-molecule fluorescence resonance energy transfer (smFRET) between (Cy5)EF-G and (Cy3)tRNA(Lys), we studied the translational elongation dynamics of -1PRF in the Escherichia coli dnaX gene, which contains three frameshifting signals: a slippery sequence (A AAA AAG), a Shine-Dalgarno (SD) sequence and a downstream hairpin. The frameshift promoting signals mostly impair the EF-G-catalyzed translocation step of the two tRNA(Lys) and the slippery codons from the A- and P- sites. The hairpin acts as a road block slowing the translocation rate. The upstream SD sequence together with the hairpin promotes dissociation of futile EF-G and thus causes multiple EF-G driven translocation attempts. A slippery sequence also helps dissociation of the EF-G by providing alternative base-pairing options. These results indicate that frameshifting takes place during the repetitive ribosomal conformational changes associated with EF-G dissociation upon unsuccessful translocation attempts of the second slippage codon from the A- to the P- sites.",2017 Mar 17,"['Kim, Hee-Kyung', 'Tinoco, Ignacio']",Nucleic Acids Res,,,False
80786183397e485664fd049d086f6e3e38ba210f,PMC,In Vitro Cell Death Determination for Drug Discovery: A Landscape Review of Real Issues,http://dx.doi.org/10.1177/1179670717691251,PMC5392044,28469473,CC BY-NC,"Cell death plays a crucial role for a myriad of physiological processes, and several human diseases such as cancer are characterized by its deregulation. There are many methods available for both quantifying and qualifying the accurate process of cell death which occurs. Choosing the right assay tool is essential to generate meaningful data, provide sufficient information for clinical applications, and understand cell death processes. In vitro cell death assays are important steps in the search for new therapies against cancer as the ultimate goal remains the elaboration of drugs that interfere with specific cell death mechanisms. However, choosing a cell viability or cytotoxicity assay among the many available options is a daunting task. Indeed, cell death can be approached by several viewpoints and require a more holistic approach. This review provides an overview of cell death assays usually used in vitro for assessing cell death so as to elaborate new potential chemotherapeutics and discusses considerations for using each assay.",2017 Feb 24,"['Méry, Benoite', 'Guy, Jean-Baptiste', 'Vallard, Alexis', 'Espenel, Sophie', 'Ardail, Dominique', 'Rodriguez-Lafrasse, Claire', 'Rancoule, Chloé', 'Magné, Nicolas']",J Cell Death,,,True
13e343269547d19b3be05976232fd5cd627e1d80,PMC,Cost-effectiveness analysis of oral versus intravenous drip infusion of levofloxacin in the treatment of acute lower respiratory tract infection in Chinese elderly patients,http://dx.doi.org/10.2147/CIA.S127009,PMC5396833,28442897,CC BY-NC,"AIM: Pharmacoeconomic cost-effectiveness analysis of two different dosage regimens of levofloxacin in the treatment of acute lower respiratory tract infection in elderly patients. METHODS: A total of 108 elderly patients with acute lower respiratory tract infection who visited by our hospital between September 2013 and September 2014 were randomly divided into Group A and Group B, with 54 patients in each group. In Group A, levofloxacin injection was given for continuous intravenous infusion treatment, whereas in Group B, levofloxacin injection and levofloxacin capsule were given as sequential therapy (ST). The period of treatment for both the groups was 10 days, and minimum cost analysis was used to analyze the treatment. RESULTS: Groups A and B had cure rates of 61.1% and 59.3% (P>0.05), effective rates of 88.9% and 83.3% (P>0.05), bacterial clearance rates of 96.3% and 92.6% (P>0.05), and incidence rates of adverse reactions of 7.4% and 3.7% (P>0.05), respectively. Treatment costs of Groups A and B were 1,588 RMB and 1,150 RMB, respectively, whereas the cost-effectiveness of the two groups was at 17.86 and 13.81, respectively (P<0.05). CONCLUSION: Levofloxacin ST had relatively higher cost-effectiveness ratio for the treatment of acute lower respiratory tract infection in elderly patients, especially Chinese.",2017 Apr 12,"['Zhang, Libin', 'Hu, Ping']",Clin Interv Aging,,,True
ff292a9fce88c9c34f9ffe636729dc31c20cf300,PMC,Effect of acetate Ringer(’)s solution with or without 5% dextrose administered intravenously to diarrheic calves,http://dx.doi.org/10.1292/jvms.16-0297,PMC5402204,28302938,CC BY-NC-ND,"The objectives of this study were to evaluate the effects of intravenous acetate Ringer’s solution, with or without dextrose, on diarrheic calves with either experimentally induced or spontaneous diarrhea. In the experimental model, diarrhea was induced in nine healthy calves by administering cold milk (below 4°C) twice a day for 2 days. The calves were randomly assigned to the isotonic saline (ISS), acetated Ringer’s (AR) or acetated Ringer’s with 5% dextrose (ARD) groups, with three calves assigned to each group. The calves received 80 ml/kg of their designated solution, at a flow rate of 20 ml/kg/hr. Infusion of ISS, AR and ARD were all found to be safe and effective in increasing plasma volume. Intravenous (IV) infusion of ISS resulted in the acidification secondary to dilution, while AR and ARD infusion inhibited acidification. In addition, prevention of catabolism was observed only with IV infusion of ARD. Sixteen calves with spontaneous diarrhea were enrolled in the clinical study. The calves were randomly assigned to the AR or ARD groups, with eight calves being assigned to each group. The calves received 100 ml/kg of their designated solution, at a flow rate of 25 ml/kg/hr. Intravenous infusion of AR and ARD was found to be effective in increasing plasma volume and inhibiting acidification. Only infusion of ARD prevented catabolism, but it also led to hyperglycemia. Our results suggest that a solution containing dextrose may be beneficial for wasting diarrheic calves.",2017 Apr 12,"['TSUKANO, Kenji', 'KATO, Satoko', 'SARASHINA, Shinya', 'ABE, Izumi', 'AJITO, Tadaharu', 'OHTSUKA, Hiromichi', 'SUZUKI, Kazuyuki']",J Vet Med Sci,,,True
949ec05f3fbd741cc6c4a08b2bcffdaa3d479866,PMC,Pseudotyping exosomes for enhanced protein delivery in mammalian cells,http://dx.doi.org/10.2147/IJN.S133430,PMC5402897,28458537,CC BY-NC,"Exosomes are cell-derived nanovesicles that hold promise as living vehicles for intracellular delivery of therapeutics to mammalian cells. This potential, however, is undermined by the lack of effective methods to load exosomes with therapeutic proteins and to facilitate their uptake by target cells. Here, we demonstrate how a vesicular stomatitis virus glycoprotein (VSVG) can both load protein cargo onto exosomes and increase their delivery ability via a pseudotyping mechanism. By fusing a set of fluorescent and luminescent reporters with VSVG, we show the successful targeting and incorporation of VSVG fusions into exosomes by gene transfection and fluorescence tracking. We subsequently validate our system by live cell imaging of VSVG and its participation in endosomes/exosomes that are ultimately released from transfected HEK293 cells. We show that VSVG pseudotyping of exosomes does not affect the size or distributions of the exosomes, and both the full-length VSVG and the VSVG without the ectodomain are shown to integrate into the exosomal membrane, suggesting that the ectodomain is not required for protein loading. Finally, exosomes pseudotyped with full-length VSVG are internalized by multiple-recipient cell types to a greater degree compared to exosomes loaded with VSVG without the ectodomain, confirming a role of the ectodomain in cell tropism. In summary, our work introduces a new genetically encoded pseudotyping platform to load and enhance the intracellular delivery of therapeutic proteins via exosome-based vehicles to target cells.",2017 Apr 18,"['Meyer, Conary', 'Losacco, Joseph', 'Stickney, Zachary', 'Li, Lingxuan', 'Marriott, Gerard', 'Lu, Biao']",Int J Nanomedicine,,,True
27ee5b4647398fd11e7044166a9d68aca391ebcf,PMC,Cellular Antiviral Factors that Target Particle Infectivity of HIV-1,http://dx.doi.org/10.2174/1570162X14666151216145521,PMC5403965,26674651,CC BY-NC,"Background: In the past decade, the identification and characterization of antiviral genes with the ability to interfere with virus replication has established cell-intrinsic innate immunity as a third line of antiviral defense in addition to adaptive and classical innate immunity. Understanding how cellular factors have evolved to inhibit HIV-1 reveals particularly vulnerable points of the viral replication cycle. Many, but not all, antiviral proteins share type I interferon-upregulated expression and sensitivity to viral counteraction or evasion measures. Whereas well-established restriction factors interfere with early post-entry steps and release of HIV-1, recent research has revealed a diverse set of proteins that reduce the infectious quality of released particles using individual, to date poorly understood modes of action. These include induction of paucity of mature glycoproteins in nascent virions or self-incorporation into the virus particle, resulting in poor infectiousness of the virion and impaired spread of the infection. Conclusion: A better understanding of these newly discovered antiviral factors may open new avenues towards the design of drugs that repress the spread of viruses whose genomes have already integrated.",2016 May,"Goffinet, Christine",Curr HIV Res,,,True
058e306088e83c58ee30b43f0e102a45463351fe,PMC,Risk and Outbreak Communication: Lessons from Taiwan's Experiences in the Post-SARS Era,http://dx.doi.org/10.1089/hs.2016.0111,PMC5404243,28418746,CC BY-NC,"In addition to the impact of a disease itself, public reaction could be considered another outbreak to be controlled during an epidemic. Taiwan's experience with SARS in 2003 highlighted the critical role played by the media during crisis communication. After the SARS outbreak, Taiwan's Centers for Disease Control (Taiwan CDC) followed the WHO outbreak communication guidelines on trust, early announcements, transparency, informing the public, and planning, in order to reform its risk communication systems. This article describes the risk communication framework in Taiwan, which has been used to respond to the 2009-2016 influenza epidemics, Ebola in West Africa (2014-16), and MERS-CoV in South Korea (2015) during the post-SARS era. Many communication strategies, ranging from traditional media to social and new media, have been implemented to improve transparency in public communication and promote civic engagement. Taiwan CDC will continue to maintain the strengths of its risk communication systems and resolve challenges as they emerge through active evaluation and monitoring of public opinion to advance Taiwan's capacity in outbreak communication and control. Moreover, Taiwan CDC will continue to implement the IHR (2005) and to promote a global community working together to fight shared risks and to reach the goal of “One World, One Health.”",2017 Apr 1,"['Hsu, Yu-Chen', 'Chen, Yu-Ling', 'Wei, Han-Ning', 'Yang, Yu-Wen', 'Chen, Ying-Hwei']",Health Secur,,,True
3ba6e62e7ed8c087b34db8520cb1a203a062ded9,PMC,Public Health Emergency Response in Taiwan,http://dx.doi.org/10.1089/hs.2016.0108,PMC5404248,28418737,CC BY-NC,"In recent years, growth of international travel and trade, as well as climate change, has resulted in the frequent emergence and reemergence of infectious diseases such as Ebola, Zika, and MERS. In 2016, Taiwan used the Joint External Evaluation (JEE) tool to evaluate its public health emergency response capacities and understand important areas for improvement. This article presents Taiwan's disaster and public health emergency response organizational structure, real-time integrated information, response processes, and command center structure. After reviewing the results of the JEE tool and drawing lessons from emergency response efforts in the United States, we provide 3 recommendations that may enhance Taiwan's public health emergency response capacities: establish common principles for disaster response regardless of which agency is in charge, standardize operation procedures, and perform regular training that includes nongovernmental organizations and a range of government departments.",2017 Apr 1,"['Su, Yi-Feng', 'Wu, Cheng-Hao', 'Lee, Tsui-Feng']",Health Secur,,,True
c96149ec9735f620b4acd1c4da5c537ed2175619,PMC,Taiwan's Public Health National Laboratory System: Success in Influenza Diagnosis and Surveillance,http://dx.doi.org/10.1089/hs.2016.0104,PMC5404250,28418742,CC BY-NC,"Taiwan's National Laboratory System is one of the action packages of the Global Health Security Agenda, which was launched by the World Health Organization (WHO) to promote health security as an international priority and to encourage progress toward full implementation of the WHO International Health Regulations (IHR) 2005. The mission of each national laboratory system is to conduct real-time biosurveillance and effective laboratory-based diagnostics, as measured by a nationwide laboratory system able to reliably conduct diagnoses on specimens transported properly to designated laboratories from at least 80% of the regions in the country. In Taiwan, the national laboratory system for public health is well-established and coordinated by the Taiwan Centers for Disease Control (CDC), which is the government authority in charge of infectious disease prevention and intervention. Through the national laboratory system, Taiwan CDC effectively detects and characterizes pathogens that cause communicable diseases across the entire country, including both known and novel threats, and also conducts epidemiologic analyses of infectious diseases. In this article, we describe the national laboratory system for public health in Taiwan. We provide additional information on the national influenza laboratory surveillance network to demonstrate how our national laboratory systems work in practice, including descriptions of long-term seasonal influenza characterization and successful experiences identifying novel H7N9 and H6N1 influenza viruses.",2017 Apr 1,"['Yang, Ji-Rong', 'Teng, Hwa-Jen', 'Liu, Ming-Tsan', 'Li, Shu-Ying']",Health Secur,,,True
fd90269a5594e3c1c8d7c98e497070eedef35213,PMC,Stockpile Model of Personal Protective Equipment in Taiwan,http://dx.doi.org/10.1089/hs.2016.0103,PMC5404251,28418743,CC BY-NC,"The Taiwan Centers for Disease Control (Taiwan CDC) has established a 3-tier personal protective equipment (PPE) stockpiling framework that could maintain a minimum stockpile for the surge demand of PPE in the early stage of a pandemic. However, PPE stockpiling efforts must contend with increasing storage fees and expiration problems. In 2011, the Taiwan CDC initiated a stockpile replacement model in order to optimize the PPE stockpiling efficiency, ensure a minimum stockpile, use the government's limited funds more effectively, and achieve the goal of sustainable management. This stockpile replacement model employs a first-in-first-out principle in which the oldest stock in the central government stockpile is regularly replaced and replenished with the same amount of new and qualified products, ensuring the availability and maintenance of the minimum stockpiles. In addition, a joint electronic procurement platform has been established for merchandising the replaced PPE to local health authorities and medical and other institutions for their routine or epidemic use. In this article, we describe the PPE stockpile model in Taiwan, including the 3-tier stockpiling framework, the operational model, the components of the replacement system, implementation outcomes, epidemic supports, and the challenges and prospects of this model.",2017 Apr 1,"['Chen, Yu-Ju', 'Chiang, Po-Jung', 'Cheng, Yu-Hsin', 'Huang, Chun-Wei', 'Kao, Hui-Yun', 'Chang, Chih-Kai', 'Huang, Hsun-Miao', 'Liu, Pei-Yin', 'Wang, Jen-Hsin', 'Chih, Yi-Chien', 'Chou, Shu-Mei', 'Yang, Chin-Hui', 'Chen, Chang-Hsun']",Health Secur,,,True
cc6cb3af2ef6432cf20dd2c84b56fdb8be780078,PMC,Taiwan's Experience in Hospital Preparedness and Response for Emerging Infectious Diseases,http://dx.doi.org/10.1089/hs.2016.0105,PMC5404255,28418745,CC BY-NC,"The Communicable Disease Control Medical Network (CDCMN), established in 2003 after the SARS outbreak in Taiwan, has undergone several phases of modification in structure and activation. The main organizing principles of the CDCMN are centralized isolation of patients with severe highly infectious diseases and centralization of medical resources, as well as a network of designated regional hospitals like those in other countries. The CDCMN is made up of a command system, responding hospitals, and supporting hospitals. It was tested and activated in response to the H1N1 influenza pandemic in 2009-10 and the Ebola outbreak in West Africa in 2014-2016, and it demonstrated high-level functioning and robust capacity. In this article, the history, structure, and operation of the CDCMN is introduced globally for the first time, and the advantages and challenges of this system are discussed. The Taiwanese experience shows an example of a collaboration between the public health system and the medical system that may help other public health authorities plan management and hospital preparedness for highly infectious diseases.",2017 Apr 1,"['Kao, Hui-Yun', 'Ko, Hai-Yun', 'Guo, Peng', 'Chen, Chang-Hsun', 'Chou, Su-Mei']",Health Secur,,,True
64d31d4587a86108556e52c45e1ea3750fa7303f,PMC,Implementation of the IHR Joint External Evaluation: Taiwan's Experiences,http://dx.doi.org/10.1089/hs.2016.0093,PMC5404271,28418741,CC BY-NC,"In February 2016, the World Health Organization developed the Joint External Evaluation (JEE) tool to independently assess country capacity to prevent, detect, and respond to public health threats as part of the International Health Regulations (IHR) (2005) monitoring and evaluation framework. In light of this, the Taiwan government actively engaged at least 19 government agencies or institutions and voluntarily implemented the JEE. An External Assessment Team consisting of 6 US subject matter experts conducted the external evaluation, including site visits, from June 21 to July 1, 2016. The results, published on October 18, 2016, are useful and will be translated into actions and change in the system. Based on Taiwan's experiences, early stakeholder engagement and an experts' pre-JEE pilot visit would contribute to a successful JEE process.",2017 Apr 1,"Lo, Yi-Chun",Health Secur,,,True
16320b30b2f068bc2d7bc9cf2f2da87261f041b4,PMC,A case of acute acquired obstructive hydrocephalus in a cat with suspected ischaemic cerebellar infarct,http://dx.doi.org/10.1177/2055116917704089,PMC5405888,28491457,CC BY-NC,"CASE SUMMARY: A case of acquired acute obstructive hydrocephalus that developed as a complication of an ischaemic infarct in the vascular territory of the rostral cerebellar artery is described in an adult domestic shorthair cat. The clinical findings, diagnostic investigations, treatment and prognosis are reported. MRI findings are described in detail. RELEVANCE AND NOVEL INFORMATION: This is the first report of obstructive hydrocephalus as a complication of an ischaemic infarct in the region of the rostral cerebellar artery in a cat. MRI findings are described in detail with regard to the recognition of the early signs of obstructive hydrocephalus. A brief review of the literature is included, as this complication has been frequently reported in humans.",2017 Apr 10,"['Raimondi, Francesca', 'Lourinho, Filipa', 'Scott, Harry', 'Shihab, Nadia']",JFMS Open Rep,,,True
7d9c27d988dd4ca25668f573e610145140d2266e,PMC,"Virucidal Activity of World Health Organization–Recommended Formulations Against Enveloped Viruses, Including Zika, Ebola, and Emerging Coronaviruses",http://dx.doi.org/10.1093/infdis/jix046,PMC5407053,28453839,CC BY-NC-ND,"The World Health Organization (WHO) published 2 alcohol-based formulations to be used in healthcare settings and for outbreak-associated infections, but inactivation efficacies of these products have not been determined against (re-)emerging viruses. In this study, we evaluated the virucidal activity of these WHO products in a comparative analysis. Zika virus (ZIKV), Ebola virus (EBOV), severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV) as (re-)emerging viral pathogens and other enveloped viruses could be efficiently inactivated by both WHO formulations, implicating their use in healthcare systems and viral outbreak situations.",2017 Mar 15,"['Siddharta, Anindya', 'Pfaender, Stephanie', 'Vielle, Nathalie Jane', 'Dijkman, Ronald', 'Friesland, Martina', 'Becker, Britta', 'Yang, Jaewon', 'Engelmann, Michael', 'Todt, Daniel', 'Windisch, Marc P.', 'Brill, Florian H.', 'Steinmann, Joerg', 'Steinmann, Jochen', 'Becker, Stephan', 'Alves, Marco P.', 'Pietschmann, Thomas', 'Eickmann, Markus', 'Thiel, Volker', 'Steinmann, Eike']",J Infect Dis,,,True
d443900c4eef6494eeaf138236a955c0a040f3bd,PMC,Clinical usefulness of serum procalcitonin level in distinguishing between Kawasaki disease and other infections in febrile children,http://dx.doi.org/10.3345/kjp.2017.60.4.112,PMC5410617,28461824,CC BY-NC,"PURPOSE: The aims of this study were to compare serum procalcitonin (PCT) levels between febrile children with Kawasaki disease (KD) and those with bacterial or viral infections, and assess the clinical usefulness of PCT level in predicting KD. METHODS: Serum PCT levels were examined in febrile pediatric patients admitted between August 2013 and August 2014. The patients were divided into 3 groups as follows: 49 with KD, 111 with viral infections, and 24 with bacterial infections. RESULTS: The mean PCT level in the KD group was significantly lower than that in the bacterial infection group (0.82±1.73 ng/mL vs. 3.11±6.10 ng/mL, P=0.002) and insignificantly different from that in the viral infection group (0.23±0.34 ng/mL,P=0.457). The mean erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level in the KD group were significantly higher than those in the viral and bacterial infection groups (P<0.001 and P<0.001 for ESR, P<0.001 and P=0.005 for CRP, respectively). The proportion of patients in the KD group with PCT levels of >1.0 ng/mL was significantly higher in the nonresponders to the initial intravenous immunoglobulin treatment than in the responders (36% vs. 8%, P=0.01). CONCLUSION: PCT levels may help to differentiate KD from bacterial infections. A combination of disease markers, including ESR, CRP, and PCT, may be useful for differentiating between KD and viral/bacterial infections.",2017 Apr 25,"['Lee, Na Hyun', 'Choi, Hee Joung', 'Kim, Yeo Hyang']",Korean J Pediatr,,,True
5a1a3d864a2110b730b3cbf6b7a1c01a0870be42,PMC,An In-Silico Investigation of Phytochemicals as Antiviral Agents Against Dengue Fever,http://dx.doi.org/10.2174/1386207319666160506123715,PMC5411999,27151482,CC BY-NC,"Abstract: A virtual screening analysis of our library of phytochemical structures with dengue virus protein targets has been carried out using a molecular docking approach. A total of 2194 plant-derived secondary metabolites have been docked. This molecule set comprised of 290 alkaloids (68 indole alkaloids, 153 isoquinoline alkaloids, 5 quinoline alkaloids, 13 piperidine alkaloids, 14 steroidal alkaloids, and 37 miscellaneous alkaloids), 678 terpenoids (47 monoterpenoids, 169 sesquiterpenoids, 265 diterpenoids, 81 steroids, and 96 triterpenoids), 20 aurones, 81 chalcones, 349 flavonoids, 120 isoflavonoids, 74 lignans, 58 stilbenoids, 169 miscellaneous polyphenolic compounds, 100 coumarins, 28 xanthones, 67 quinones, and 160 miscellaneous phytochemicals. Dengue virus protein targets examined included dengue virus protease (NS2B-NS3pro), helicase (NS3 helicase), methyltransferase (MTase), RNA-dependent RNA polymerase (RdRp), and the dengue virus envelope protein. Polyphenolic compounds, flavonoids, chalcones, and other phenolics were the most numerous of the strongly docking ligands for dengue virus protein targets.",2016 Aug,"['Powers, Chelsea N.', 'Setzer, William N.']",Comb Chem High Throughput Screen,,,True
a7aaf2c3f905813cd23b5ac719d49e662063edb9,PMC,"Bioaerosol Sampling in Clinical Settings: A Promising, Noninvasive Approach for Detecting Respiratory Viruses",http://dx.doi.org/10.1093/ofid/ofw259,PMC5413998,28480252,CC BY-NC-ND,"BACKGROUND. Seeking a noninvasive method to conduct surveillance for respiratory pathogens, we sought to examine the usefulness of 2 types of off-the-shelf aerosol samplers to detect respiratory viruses in Singapore. METHODS. In this pilot study, we ran the aerosol samplers several times each week with patients present in the patient waiting areas at 3 primary health clinics during the months of April and May 2016. We used a SKC BioSampler with a BioLite Air Sampling Pump (run for 60 min at 8 L/min) and SKC AirChek TOUCH personal air samplers with polytetrafluoroethylene Teflon filter cassettes (run for 180 min at 5 L/min). The aerosol specimens and controls were studied with molecular assays for influenza A virus, influenza B virus, adenoviruses, and coronaviruses. RESULTS. Overall, 16 (33.3%) of the 48 specimens indicated evidence of at least 1 respiratory pathogen, with 1 (2%) positive for influenza A virus, 3 (6%) positive for influenza B virus, and 12 (25%) positive for adenovirus. CONCLUSIONS. Although we were not able to correlate molecular detection with individual patient illness, patients with common acute respiratory illnesses were present during the samplings. Combined with molecular assays, it would suggest that aerosol sampling has potential as a noninvasive method for novel respiratory virus detection in clinical settings.",2016 Dec 26,"['Nguyen, Tham T.', 'Poh, Mee K.', 'Low, Jenny', 'Kalimuddin, Shirin', 'Thoon, Koh C.', 'Ng, Wai C.', 'Anderson, Benjamin D.', 'Gray, Gregory C.']",Open Forum Infect Dis,,,True
82b0cd320ba1e619c08fee764bec158f166fab55,PMC,Pediatric Drug Nitazoxanide: A Potential Choice for Control of Zika,http://dx.doi.org/10.1093/ofid/ofx009,PMC5414027,28480282,CC BY-NC-ND,"Zika virus (ZIKV) infection can be the cause of congenital malformations, including microcephaly in infants and can cause other disorders such as Guillain-Barré syndrome, meningoencephalitis, and myelitis, which can also occur in some infected adults. However, at this time, there is no drug approved to treat ZIKV infection. Drug repurposing is the promptest way to obtain an effective drug during a global public health emergency such as the spread of Zika virus. In this study, we report a US Food and Drug Admistration-approved drug that is safe for pediatric use. Nitazoxanide and its bioactive metabolite, tizoxanide, have anti-ZIKV potential in vitro, and we identified that they exerts antiviral effect possibly by targeting the viral postattachment step.",2017 Feb 3,"['Cao, Rui-Yuan', 'Xu, Yong-fen', 'Zhang, Tian-Hong', 'Yang, Jing-Jing', 'Yuan, Ye', 'Hao, Pei', 'Shi, Yi', 'Zhong, Jin', 'Zhong, Wu']",Open Forum Infect Dis,,,True
603338700afbe7c3712312a9a67a086cfe4c35bc,PMC,Pediatric Drug Nitazoxanide: A Potential Choice for Control of Zika,http://dx.doi.org/10.1093/ofid/ofx009,PMC5414027,28480282,CC BY-NC-ND,"Zika virus (ZIKV) infection can be the cause of congenital malformations, including microcephaly in infants and can cause other disorders such as Guillain-Barré syndrome, meningoencephalitis, and myelitis, which can also occur in some infected adults. However, at this time, there is no drug approved to treat ZIKV infection. Drug repurposing is the promptest way to obtain an effective drug during a global public health emergency such as the spread of Zika virus. In this study, we report a US Food and Drug Admistration-approved drug that is safe for pediatric use. Nitazoxanide and its bioactive metabolite, tizoxanide, have anti-ZIKV potential in vitro, and we identified that they exerts antiviral effect possibly by targeting the viral postattachment step.",2017 Feb 3,"['Cao, Rui-Yuan', 'Xu, Yong-fen', 'Zhang, Tian-Hong', 'Yang, Jing-Jing', 'Yuan, Ye', 'Hao, Pei', 'Shi, Yi', 'Zhong, Jin', 'Zhong, Wu']",Open Forum Infect Dis,,,False
1254a21897ff699773d968bd86bf34da44c0ebc5,PMC,Pediatric Drug Nitazoxanide: A Potential Choice for Control of Zika,http://dx.doi.org/10.1093/ofid/ofx009,PMC5414027,28480282,CC BY-NC-ND,"Zika virus (ZIKV) infection can be the cause of congenital malformations, including microcephaly in infants and can cause other disorders such as Guillain-Barré syndrome, meningoencephalitis, and myelitis, which can also occur in some infected adults. However, at this time, there is no drug approved to treat ZIKV infection. Drug repurposing is the promptest way to obtain an effective drug during a global public health emergency such as the spread of Zika virus. In this study, we report a US Food and Drug Admistration-approved drug that is safe for pediatric use. Nitazoxanide and its bioactive metabolite, tizoxanide, have anti-ZIKV potential in vitro, and we identified that they exerts antiviral effect possibly by targeting the viral postattachment step.",2017 Feb 3,"['Cao, Rui-Yuan', 'Xu, Yong-fen', 'Zhang, Tian-Hong', 'Yang, Jing-Jing', 'Yuan, Ye', 'Hao, Pei', 'Shi, Yi', 'Zhong, Jin', 'Zhong, Wu']",Open Forum Infect Dis,,,False
4d5d980d7d2b13a02abfb6e9706c9390ebb86353,PMC,Pediatric Drug Nitazoxanide: A Potential Choice for Control of Zika,http://dx.doi.org/10.1093/ofid/ofx009,PMC5414027,28480282,CC BY-NC-ND,"Zika virus (ZIKV) infection can be the cause of congenital malformations, including microcephaly in infants and can cause other disorders such as Guillain-Barré syndrome, meningoencephalitis, and myelitis, which can also occur in some infected adults. However, at this time, there is no drug approved to treat ZIKV infection. Drug repurposing is the promptest way to obtain an effective drug during a global public health emergency such as the spread of Zika virus. In this study, we report a US Food and Drug Admistration-approved drug that is safe for pediatric use. Nitazoxanide and its bioactive metabolite, tizoxanide, have anti-ZIKV potential in vitro, and we identified that they exerts antiviral effect possibly by targeting the viral postattachment step.",2017 Feb 3,"['Cao, Rui-Yuan', 'Xu, Yong-fen', 'Zhang, Tian-Hong', 'Yang, Jing-Jing', 'Yuan, Ye', 'Hao, Pei', 'Shi, Yi', 'Zhong, Jin', 'Zhong, Wu']",Open Forum Infect Dis,,,False
177f19cb851d56dd54b2bb6306d506798dd7ceca,PMC,Pediatric Drug Nitazoxanide: A Potential Choice for Control of Zika,http://dx.doi.org/10.1093/ofid/ofx009,PMC5414027,28480282,CC BY-NC-ND,"Zika virus (ZIKV) infection can be the cause of congenital malformations, including microcephaly in infants and can cause other disorders such as Guillain-Barré syndrome, meningoencephalitis, and myelitis, which can also occur in some infected adults. However, at this time, there is no drug approved to treat ZIKV infection. Drug repurposing is the promptest way to obtain an effective drug during a global public health emergency such as the spread of Zika virus. In this study, we report a US Food and Drug Admistration-approved drug that is safe for pediatric use. Nitazoxanide and its bioactive metabolite, tizoxanide, have anti-ZIKV potential in vitro, and we identified that they exerts antiviral effect possibly by targeting the viral postattachment step.",2017 Feb 3,"['Cao, Rui-Yuan', 'Xu, Yong-fen', 'Zhang, Tian-Hong', 'Yang, Jing-Jing', 'Yuan, Ye', 'Hao, Pei', 'Shi, Yi', 'Zhong, Jin', 'Zhong, Wu']",Open Forum Infect Dis,,,False
5699971f98dab3c45f237878901e4c8b247bc234,PMC,"Hospital-Acquired Respiratory Viral Infections: Incidence, Morbidity, and Mortality in Pediatric and Adult Patients",http://dx.doi.org/10.1093/ofid/ofx006,PMC5414085,28480279,CC BY-NC-ND,"BACKGROUND. Hospital-acquired respiratory viral infections can result in morbidity and mortality of hospitalized patients. This study was undertaken to better understand the magnitude of the problem of nosocomial respiratory viral infections in adult and pediatric patients. METHODS. This was a retrospective study at a tertiary care adult and pediatric teaching hospital. Study patients met a priori criteria for definite or possible nosocomial respiratory viral infection. RESULTS. From April 1, 2015 to April 1, 2016, we identified 40 nosocomial respiratory viral infections in 38 patients involving 14 definite and 3 possible cases in our adult hospital and 18 definite and 5 possible cases in our pediatric hospital. The incidence was 5 cases/10 000 admissions and 44 cases/10 000 admissions to our adult and pediatric hospitals, respectively. Only 6.8% of cases were due to influenza. Although 63% of cases occurred during the fall and winter, such infections were identified throughout the year. Five (13%) nosocomial respiratory viral infections occurred in 2 adult and 3 pediatric patients who died during the hospitalization. CONCLUSIONS. Nosocomial respiratory viral infections are an underappreciated cause of morbidity and mortality in hospitalized adult and pediatric patients. The incidence was nearly 10-fold higher in our pediatric hospital. We estimate there are approximately 18 955 pediatric and adult cases of nosocomial respiratory viral infections in US acute care hospitals each year.",2017 Feb 3,"['Chow, Eric J.', 'Mermel, Leonard A.']",Open Forum Infect Dis,,,True
a8002f42a29667524fe9cae0a0a94f60fbbf6079,PMC,Crossed fused renal ectopia in a Persian cat,http://dx.doi.org/10.1177/2055116917695875,PMC5415293,28491454,CC BY-NC,"CASE SUMMARY: This report describes a rare case of crossed fused renal ectopia (CFRE) in a cat. A mature intact male Persian cat presented with bloody nasal discharge and ascites. Diagnostic studies revealed an ectopic left kidney fused with an orthotopic right kidney and a concurrent feline infectious peritonitis (FIP) infection. The FIP was responsible for clinical signs in this cat, while clinical signs associated with CFRE were not obvious. Despite receiving intensive treatment, the cat died. A post-mortem examination was not performed because the owners declined approval. RELEVANCE AND NOVEL INFORMATION: To the best of our knowledge, this is the first report of L-shaped CFRE in a cat. In addition, this report describes the CT features of L-shaped CFRE in a cat.",2017 Mar 14,"['Seo, Sang-Hyuk', 'Lee, Hyun-A', 'Suh, Sang-Il', 'Choi, Ran', 'Park, In-Chul', 'Hyun, Changbaig']",JFMS Open Rep,,,True
1780b05d86758cff5cd62198323366bee36f59e5,PMC,Toward Personalized Gene Therapy: Characterizing the Host Genetic Control of Lentiviral-Vector-Mediated Hepatic Gene Delivery,http://dx.doi.org/10.1016/j.omtm.2017.03.009,PMC5415322,28480308,CC BY-NC-ND,"The success of lentiviral vectors in curing fatal genetic and acquired diseases has opened a new era in human gene therapy. However, variability in the efficacy and safety of this therapeutic approach has been reported in human patients. Consequently, lentiviral-vector-based gene therapy is limited to incurable human diseases, with little understanding of the underlying causes of adverse effects and poor efficacy. To assess the role that host genetic variation has on efficacy of gene therapy, we characterized lentiviral-vector gene therapy within a set of 12 collaborative cross mouse strains. Lentiviral vectors carrying the firefly luciferase cDNA under the control of a liver-specific promoter were administered to female mice, with total-body and hepatic luciferase expression periodically monitored through 41 weeks post-vector administration. Vector copy number per diploid genome in mouse liver and spleen was determined at the end of this study. We identified major strain-specific contributions to overall success of transduction, vector biodistribution, maximum luciferase expression, and the kinetics of luciferase expression throughout the study. Our results highlight the importance of genetic variation on gene-therapeutic efficacy; provide new models with which to more rigorously assess gene therapy approaches; and suggest that redesigning preclinical studies of gene-therapy methodologies might be appropriate.",2017 Apr 5,"['Suwanmanee, Thipparat', 'Ferris, Martin T.', 'Hu, Peirong', 'Gui, Tong', 'Montgomery, Stephanie A.', 'Pardo-Manuel de Villena, Fernando', 'Kafri, Tal']",Mol Ther Methods Clin Dev,,,False
59b270a8f43274cb9c68e16cac2ea6af110c452c,PMC,Toward Personalized Gene Therapy: Characterizing the Host Genetic Control of Lentiviral-Vector-Mediated Hepatic Gene Delivery,http://dx.doi.org/10.1016/j.omtm.2017.03.009,PMC5415322,28480308,CC BY-NC-ND,"The success of lentiviral vectors in curing fatal genetic and acquired diseases has opened a new era in human gene therapy. However, variability in the efficacy and safety of this therapeutic approach has been reported in human patients. Consequently, lentiviral-vector-based gene therapy is limited to incurable human diseases, with little understanding of the underlying causes of adverse effects and poor efficacy. To assess the role that host genetic variation has on efficacy of gene therapy, we characterized lentiviral-vector gene therapy within a set of 12 collaborative cross mouse strains. Lentiviral vectors carrying the firefly luciferase cDNA under the control of a liver-specific promoter were administered to female mice, with total-body and hepatic luciferase expression periodically monitored through 41 weeks post-vector administration. Vector copy number per diploid genome in mouse liver and spleen was determined at the end of this study. We identified major strain-specific contributions to overall success of transduction, vector biodistribution, maximum luciferase expression, and the kinetics of luciferase expression throughout the study. Our results highlight the importance of genetic variation on gene-therapeutic efficacy; provide new models with which to more rigorously assess gene therapy approaches; and suggest that redesigning preclinical studies of gene-therapy methodologies might be appropriate.",2017 Apr 5,"['Suwanmanee, Thipparat', 'Ferris, Martin T.', 'Hu, Peirong', 'Gui, Tong', 'Montgomery, Stephanie A.', 'Pardo-Manuel de Villena, Fernando', 'Kafri, Tal']",Mol Ther Methods Clin Dev,,,False
88e67f8fd299210867da50bb0879c8a3d8a65e65,PMC,Toward Personalized Gene Therapy: Characterizing the Host Genetic Control of Lentiviral-Vector-Mediated Hepatic Gene Delivery,http://dx.doi.org/10.1016/j.omtm.2017.03.009,PMC5415322,28480308,CC BY-NC-ND,"The success of lentiviral vectors in curing fatal genetic and acquired diseases has opened a new era in human gene therapy. However, variability in the efficacy and safety of this therapeutic approach has been reported in human patients. Consequently, lentiviral-vector-based gene therapy is limited to incurable human diseases, with little understanding of the underlying causes of adverse effects and poor efficacy. To assess the role that host genetic variation has on efficacy of gene therapy, we characterized lentiviral-vector gene therapy within a set of 12 collaborative cross mouse strains. Lentiviral vectors carrying the firefly luciferase cDNA under the control of a liver-specific promoter were administered to female mice, with total-body and hepatic luciferase expression periodically monitored through 41 weeks post-vector administration. Vector copy number per diploid genome in mouse liver and spleen was determined at the end of this study. We identified major strain-specific contributions to overall success of transduction, vector biodistribution, maximum luciferase expression, and the kinetics of luciferase expression throughout the study. Our results highlight the importance of genetic variation on gene-therapeutic efficacy; provide new models with which to more rigorously assess gene therapy approaches; and suggest that redesigning preclinical studies of gene-therapy methodologies might be appropriate.",2017 Apr 5,"['Suwanmanee, Thipparat', 'Ferris, Martin T.', 'Hu, Peirong', 'Gui, Tong', 'Montgomery, Stephanie A.', 'Pardo-Manuel de Villena, Fernando', 'Kafri, Tal']",Mol Ther Methods Clin Dev,,,False
8884a33d015cfe35ba1d0df44c0cc33c8e5a23c1,PMC,Translation of Angiotensin-Converting Enzyme 2 upon Liver- and Lung-Targeted Delivery of Optimized Chemically Modified mRNA,http://dx.doi.org/10.1016/j.omtn.2017.04.006,PMC5423349,28624211,CC BY-NC-ND,"Changes in lifestyle and environmental conditions give rise to an increasing prevalence of liver and lung fibrosis, and both have a poor prognosis. Promising results have been reported for recombinant angiotensin-converting enzyme 2 (ACE2) protein administration in experimental liver and lung fibrosis. However, the full potential of ACE2 may be achieved by localized translation of a membrane-anchored form. For this purpose, we advanced the latest RNA technology for liver- and lung-targeted ACE2 translation. We demonstrated in vitro that transfection with ACE2 chemically modified messenger RNA (cmRNA) leads to robust translation of fully matured, membrane-anchored ACE2 protein. In a second step, we designed eight modified ACE2 cmRNA sequences and identified a lead sequence for in vivo application. Finally, formulation of this ACE2 cmRNA in tailor-made lipidoid nanoparticles and in lipid nanoparticles led to liver- and lung-targeted translation of significant amounts of ACE2 protein, respectively. In summary, we provide evidence that RNA transcript therapy (RTT) is a promising approach for ACE2-based treatment of liver and lung fibrosis to be tested in fibrotic disease models.",2017 Apr 13,"['Schrom, Eva', 'Huber, Maja', 'Aneja, Manish', 'Dohmen, Christian', 'Emrich, Daniela', 'Geiger, Johannes', 'Hasenpusch, Günther', 'Herrmann-Janson, Annika', 'Kretzschmann, Verena', 'Mykhailyk, Olga', 'Pasewald, Tamara', 'Oak, Prajakta', 'Hilgendorff, Anne', 'Wohlleber, Dirk', 'Hoymann, Heinz-Gerd', 'Schaudien, Dirk', 'Plank, Christian', 'Rudolph, Carsten', 'Kubisch-Dohmen, Rebekka']",Mol Ther Nucleic Acids,,,False
b86d1ec7a2b3015d067b65ce5fe555e1cb9e3465,PMC,Translation of Angiotensin-Converting Enzyme 2 upon Liver- and Lung-Targeted Delivery of Optimized Chemically Modified mRNA,http://dx.doi.org/10.1016/j.omtn.2017.04.006,PMC5423349,28624211,CC BY-NC-ND,"Changes in lifestyle and environmental conditions give rise to an increasing prevalence of liver and lung fibrosis, and both have a poor prognosis. Promising results have been reported for recombinant angiotensin-converting enzyme 2 (ACE2) protein administration in experimental liver and lung fibrosis. However, the full potential of ACE2 may be achieved by localized translation of a membrane-anchored form. For this purpose, we advanced the latest RNA technology for liver- and lung-targeted ACE2 translation. We demonstrated in vitro that transfection with ACE2 chemically modified messenger RNA (cmRNA) leads to robust translation of fully matured, membrane-anchored ACE2 protein. In a second step, we designed eight modified ACE2 cmRNA sequences and identified a lead sequence for in vivo application. Finally, formulation of this ACE2 cmRNA in tailor-made lipidoid nanoparticles and in lipid nanoparticles led to liver- and lung-targeted translation of significant amounts of ACE2 protein, respectively. In summary, we provide evidence that RNA transcript therapy (RTT) is a promising approach for ACE2-based treatment of liver and lung fibrosis to be tested in fibrotic disease models.",2017 Apr 13,"['Schrom, Eva', 'Huber, Maja', 'Aneja, Manish', 'Dohmen, Christian', 'Emrich, Daniela', 'Geiger, Johannes', 'Hasenpusch, Günther', 'Herrmann-Janson, Annika', 'Kretzschmann, Verena', 'Mykhailyk, Olga', 'Pasewald, Tamara', 'Oak, Prajakta', 'Hilgendorff, Anne', 'Wohlleber, Dirk', 'Hoymann, Heinz-Gerd', 'Schaudien, Dirk', 'Plank, Christian', 'Rudolph, Carsten', 'Kubisch-Dohmen, Rebekka']",Mol Ther Nucleic Acids,,,False
a6937f983f10f9d99250c82204812331222557ff,PMC,Translation of Angiotensin-Converting Enzyme 2 upon Liver- and Lung-Targeted Delivery of Optimized Chemically Modified mRNA,http://dx.doi.org/10.1016/j.omtn.2017.04.006,PMC5423349,28624211,CC BY-NC-ND,"Changes in lifestyle and environmental conditions give rise to an increasing prevalence of liver and lung fibrosis, and both have a poor prognosis. Promising results have been reported for recombinant angiotensin-converting enzyme 2 (ACE2) protein administration in experimental liver and lung fibrosis. However, the full potential of ACE2 may be achieved by localized translation of a membrane-anchored form. For this purpose, we advanced the latest RNA technology for liver- and lung-targeted ACE2 translation. We demonstrated in vitro that transfection with ACE2 chemically modified messenger RNA (cmRNA) leads to robust translation of fully matured, membrane-anchored ACE2 protein. In a second step, we designed eight modified ACE2 cmRNA sequences and identified a lead sequence for in vivo application. Finally, formulation of this ACE2 cmRNA in tailor-made lipidoid nanoparticles and in lipid nanoparticles led to liver- and lung-targeted translation of significant amounts of ACE2 protein, respectively. In summary, we provide evidence that RNA transcript therapy (RTT) is a promising approach for ACE2-based treatment of liver and lung fibrosis to be tested in fibrotic disease models.",2017 Apr 13,"['Schrom, Eva', 'Huber, Maja', 'Aneja, Manish', 'Dohmen, Christian', 'Emrich, Daniela', 'Geiger, Johannes', 'Hasenpusch, Günther', 'Herrmann-Janson, Annika', 'Kretzschmann, Verena', 'Mykhailyk, Olga', 'Pasewald, Tamara', 'Oak, Prajakta', 'Hilgendorff, Anne', 'Wohlleber, Dirk', 'Hoymann, Heinz-Gerd', 'Schaudien, Dirk', 'Plank, Christian', 'Rudolph, Carsten', 'Kubisch-Dohmen, Rebekka']",Mol Ther Nucleic Acids,,,False
aefb4a29e4c933751675ed871bfa09305f1ffee2,PMC,"Digested disorder:  Quarterly intrinsic disorder digest (April-May-June, 2013)",http://dx.doi.org/10.4161/idp.27454,PMC5424790,28516028,CC BY-NC,"The current literature on intrinsically disordered proteins is overwhelming. To keep interested readers up to speed with this literature, we continue a “Digested Disorder” project and represent a series of reader’s digest type articles objectively representing the research papers and reviews on intrinsically disordered proteins. The only 2 criteria for inclusion in this digest are the publication date (a paper should be published within the covered time frame) and topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the period of April, May, and June of 2013. The papers are grouped hierarchically by topics they cover, and for each of the included paper a short description is given on its major findings.",2013 Jan 1,"['DeForte, Shelly', 'Reddy, Krishna D', 'Uversky, Vladimir N']",Intrinsically Disord Proteins,,,True
5b0eeabeded14c9e02fc7bcfacb52a8fa0b3ae3c,PMC,The alphabet of intrinsic disorder:  II. Various roles of glutamic acid in ordered and intrinsically disordered proteins,http://dx.doi.org/10.4161/idp.24684,PMC5424795,28516010,CC BY-NC,"The ability of a protein to fold into unique functional state or to stay intrinsically disordered is encoded in its amino acid sequence. Both ordered and intrinsically disordered proteins (IDPs) are natural polypeptides that use the same arsenal of 20 proteinogenic amino acid residues as their major building blocks. The exceptional structural plasticity of IDPs, their capability to exist as heterogeneous structural ensembles and their wide array of important disorder-based biological functions that complements functional repertoire of ordered proteins are all rooted within the peculiar differential usage of these building blocks by ordered proteins and IDPs. In fact, some residues (so-called disorder-promoting residues) are noticeably more common in IDPs than in sequences of ordered proteins, which, in their turn, are enriched in several order-promoting residues. Furthermore, residues can be arranged according to their “disorder promoting potencies,” which are evaluated based on the relative abundances of various amino acids in ordered and disordered proteins. This review continues a series of publications on the roles of different amino acids in defining the phenomenon of protein intrinsic disorder and concerns glutamic acid, which is the second most disorder-promoting residue.",2013 Apr 1,"Uversky, Vladimir N",Intrinsically Disord Proteins,,,True
cf809464372ccec811d156d2b9d30aa57289f40b,PMC,A preliminary study on the interaction between Asn-Gly-Arg (NGR)-modified multifunctional nanoparticles and vascular epithelial cells,http://dx.doi.org/10.1016/j.apsb.2017.02.003,PMC5430811,28540174,CC BY-NC-ND,"Previously developed Asn-Gly-Arg (NGR) peptide-modified multifunctional poly(ethyleneimine)–poly(ethylene glycol) (PEI–PEG)-based nanoparticles (TPIC) have been considered to be promising carriers for the co-delivery of DNA and doxorubicin (DOX). As a continued effort, the aim of the present study was to further evaluate the interaction between TPIC and human umbilical vein endothelial cells (HUVEC) to better understand the cellular entry mechanism. In the present investigation, experiments relevant to co-localization, endocytosis inhibitors and factors influencing the internalization were performed. Without any treatment, there was no co-localization between aminopeptidase N/CD13 (APN/CD13) and caveolin 1 (CAV1). However, co-localization between CD13 and CAV1 was observed when cells were incubated with an anti-CD13 antibody or TPIC. As compared with antibody treatment, TPIC accelerated the speed and enhanced the degree of co-localization. TPIC entered HUVEC not only together with CD13 but also together with CAV1. However, this internalization was not dependent on the enzyme activity of CD13 but could be inhibited by methyl-β-eyclodextfin (MβCD), further identifying the involvement of caveolae-mediated endocytosis (CvME). This conclusion was also verified by endocytosis inhibitor experiments.",2017 May 1,"['Liu, Chunxi', 'Liu, Tingxian', 'Yu, Xiaoyue', 'Gu, Yizhu']",Acta Pharm Sin B,,,False
d77e2f4df800eddf41d5b9f10859005ce352f820,PMC,"Incidence of acute disseminated encephalomyelitis in the Jiangsu province of China, 2008–2011",http://dx.doi.org/10.1177/2055217315594831,PMC5433407,28607697,CC BY-NC,"BACKGROUND: It is important to have an estimate of the incidence of acute disseminated encephalomyelitis (ADEM) because the incidence of ADEM is unknown and the outcomes undefined in China. OBJECTIVES: This study attempts to describe ADEM incidence in large Chinese populations located in four geographically different and moderately distant areas of the same province. METHODS: A retrospective investigation was conducted with ADEM patients in Nanjing, Nantong, Yancheng and Xuzhou. The survey was carried out in regions that might have received patients meeting the case definition of ADEM provided by the International Pediatric MS Study Group from 2008 to 2011. A total of 125 hospitals were included and 412 patients were identified through the hospital information systems (HIS). RESULTS: The incidence of ADEM was 0.32/100,000/year. There are two peaks on the age-specific ADEM rates curve. One is 0.77/100,000/year among 0- to 9-year-olds, the other is 0.45/100,000/year in those aged 50–59 years. The incidence rate found for ADEM in males was 0.34/100,000/year, and in females was 0.29/100,000/year. The highest incidence rate was in Nanjing (0.40/100,000/year). CONCLUSIONS: The average annual incidence of ADEM was 0.32/100,000/year. The peak age of onset was 50–59 years old and 0–9 years old. The incidence among males was insignificantly higher than that among females. There was no significant difference in incidence by seasonal variation.",2015 Jul 8,"['Chen, Yong', 'Ma, Fubao', 'Xu, Yuanling', 'Chu, Xuhua', 'Zhang, Jinlin']",Mult Scler J Exp Transl Clin,,,True
044d6ebfdeacd8fbdd4f039872020cd4adbbe138,PMC,Agreement Among 4 Sampling Methods to Identify Respiratory Pathogens in Dairy Calves with Acute Bovine Respiratory Disease,http://dx.doi.org/10.1111/jvim.14683,PMC5434980,28295570,CC BY-NC,"BACKGROUND: Four sampling techniques commonly are used for antemortem identification of pathogens from cattle with bovine respiratory disease (BRD): the nasal swab (NS), guarded nasopharyngeal swab (NPS), bronchoalveolar lavage (BAL), and transtracheal wash (TTW). Agreement among these methods has not been well characterized. OBJECTIVE: To evaluate agreement among TTW and NS, NPS, or BAL for identification of viral and bacterial pathogens in dairy calves with BRD. ANIMALS: One hundred dairy calves with naturally acquired BRD. METHODS: Calves were sampled by all 4 methods. Viral agents were identified by real‐time RT‐PCR, bacteria were identified by aerobic culture, and Mycoplasma bovis (M. bovis) isolates were speciated by PCR. Agreement among TTW and NS, NPS, or BAL was evaluated by calculating the kappa statistic and percent positive agreement. McNemar's exact test was used to compare the proportions of positive results. RESULTS: Agreement among TTW and NS, TTW and NPS, and TTW and BAL, was very good for identification of P. multocida, M. haemolytica, and M. bovis. For bovine respiratory syncytial virus (BRSV), agreement with TTW was moderate for NS, good for NPS, and very good for BAL. For bovine coronavirus (BCV), agreement with TTW was moderate for NS and NPS, and good for BAL. McNemar's test was significant only for BCV, indicating that for this pathogen the proportion of positive results from NS and NPS could not be considered comparable to TTW. CONCLUSIONS AND CLINICAL IMPORTANCE: This study provides guidance for veterinarians selecting diagnostic tests for antemortem identification of pathogens associated with BRD.",2017 Mar 14 May-Jun,"['Doyle, D.', 'Credille, B.', 'Lehenbauer, T.W.', 'Berghaus, R.', 'Aly, S.S.', 'Champagne, J.', 'Blanchard, P.', 'Crossley, B.', 'Berghaus, L.', 'Cochran, S.', 'Woolums, A.']",J Vet Intern Med,,,True
7af72db19cf1096560e19d5265dc5783ea8dc2cc,PMC,A Deep Nasopharyngeal Swab Versus Nonendoscopic Bronchoalveolar Lavage for Isolation of Bacterial Pathogens from Preweaned Calves With Respiratory Disease,http://dx.doi.org/10.1111/jvim.14668,PMC5435039,28425146,CC BY-NC,"BACKGROUND: Nonendoscopic bronchoalveolar lavage (BAL) is a practical alternative for a deep nasopharyngeal swab (DNS) to sample the airways of a large number of calves in a short period of time. The extent of commensal overgrowth and agreement of BAL with DNS culture results in preweaned calves are unknown. OBJECTIVES: To compare commensal overgrowth and bacterial culture results between DNS and BAL samples. ANIMALS: A total of 183 preweaned calves (144 with bovine respiratory disease and 39 healthy animals). METHODS: Cross‐sectional study. Deep nasopharyngeal swab and BAL samples were taken from each calf and cultured to detect Pasteurellaceae and Mycoplasma bovis. Agreement and associations between culture results of DNS and BAL samples were determined by kappa statistics and logistic regression. RESULTS: Bronchoalveolar lavage samples were less often polymicrobial, more frequently negative and yielded more pure cultures compared to DNS, leading to a clinically interpretable culture result in 79.2% of the cases compared to only in 31.2% of the DNS samples. Isolation rates were lower in healthy animals, but not different between DNS and BAL samples. Only Histophilus somni was more likely to be isolated from BAL samples. In clinical cases, a polymicrobial DNS culture result did not increase the probability of a polymicrobial BAL result by ≥30%, nor did it influence the probability of a negative culture. A significant herd effect was noted for all observed relationships. CONCLUSIONS AND CLINICAL RELEVANCE: Nonendoscopic BAL samples are far less overgrown by bacteria compared to DNS samples under the conditions of this study, facilitating clinical interpretation and resulting in a higher return on investment in bacteriologic culturing.",2017 Apr 19 May-Jun,"['Van Driessche, L.', 'Valgaeren, B.R.', 'Gille, L.', 'Boyen, F.', 'Ducatelle, R.', 'Haesebrouck, F.', 'Deprez, P.', 'Pardon, B.']",J Vet Intern Med,,,True
a1cdea1502a0fd90dbbff6e8a29480d856c03fed,PMC,Characterization of the Fecal Bacterial Microbiota of Healthy and Diarrheic Dairy Calves,http://dx.doi.org/10.1111/jvim.14695,PMC5435056,28390070,CC BY-NC,"BACKGROUND: Neonatal diarrhea accounts for more than 50% of total deaths in dairy calves. Few population‐based studies of cattle have investigated how the microbiota is impacted during diarrhea. OBJECTIVES: To characterize the fecal microbiota and predict the functional potential of the microbial communities in healthy and diarrheic calves. METHODS: Fifteen diarrheic calves between the ages of 1 and 30 days and 15 age‐matched healthy control calves were enrolled from 2 dairy farms. The Illumina MiSeq sequencer was used for high‐throughput sequencing of the V4 region of the 16S rRNA gene (Illumina, San Diego, CA). RESULTS: Significant differences in community membership and structure were identified among healthy calves from different farms. Differences in community membership and structure also were identified between healthy and diarrheic calves within each farm. Based on linear discriminant analysis effect size (LEfSe), the genera Bifidobacterium, Megamonas, and a genus of the family Bifidobacteriaceae were associated with health at farm 1, whereas Lachnospiraceae incertae sedis, Dietzia and an unclassified genus of the family Veillonellaceae were significantly associated with health at farm 2. The Phylogenetic Investigation of Communities Reconstruction of Unobserved States (PICRUSt) analysis indicated that diarrheic calves had decreased abundances of genes responsible for metabolism of various vitamins, amino acids, and carbohydrate. CLINICAL RELEVANCE: The fecal microbiota of healthy dairy calves appeared to be farm specific as were the changes observed during diarrhea. The differences in microbiota structure and membership between healthy and diarrheic calves suggest that dysbiosis can occur in diarrheic calves and it is associated with changes in predictive metagenomic function.",2017 Apr 7 May-Jun,"['Gomez, D.E.', 'Arroyo, L.G.', 'Costa, M.C.', 'Viel, L.', 'Weese, J.S.']",J Vet Intern Med,,,True
66b01a6dc7a215a829ad1cf82b0ab673412ecd00,PMC,Characterization of the Fecal Bacterial Microbiota of Healthy and Diarrheic Dairy Calves,http://dx.doi.org/10.1111/jvim.14695,PMC5435056,28390070,CC BY-NC,"BACKGROUND: Neonatal diarrhea accounts for more than 50% of total deaths in dairy calves. Few population‐based studies of cattle have investigated how the microbiota is impacted during diarrhea. OBJECTIVES: To characterize the fecal microbiota and predict the functional potential of the microbial communities in healthy and diarrheic calves. METHODS: Fifteen diarrheic calves between the ages of 1 and 30 days and 15 age‐matched healthy control calves were enrolled from 2 dairy farms. The Illumina MiSeq sequencer was used for high‐throughput sequencing of the V4 region of the 16S rRNA gene (Illumina, San Diego, CA). RESULTS: Significant differences in community membership and structure were identified among healthy calves from different farms. Differences in community membership and structure also were identified between healthy and diarrheic calves within each farm. Based on linear discriminant analysis effect size (LEfSe), the genera Bifidobacterium, Megamonas, and a genus of the family Bifidobacteriaceae were associated with health at farm 1, whereas Lachnospiraceae incertae sedis, Dietzia and an unclassified genus of the family Veillonellaceae were significantly associated with health at farm 2. The Phylogenetic Investigation of Communities Reconstruction of Unobserved States (PICRUSt) analysis indicated that diarrheic calves had decreased abundances of genes responsible for metabolism of various vitamins, amino acids, and carbohydrate. CLINICAL RELEVANCE: The fecal microbiota of healthy dairy calves appeared to be farm specific as were the changes observed during diarrhea. The differences in microbiota structure and membership between healthy and diarrheic calves suggest that dysbiosis can occur in diarrheic calves and it is associated with changes in predictive metagenomic function.",2017 Apr 7 May-Jun,"['Gomez, D.E.', 'Arroyo, L.G.', 'Costa, M.C.', 'Viel, L.', 'Weese, J.S.']",J Vet Intern Med,,,False
38dc0ee95e923827c1495df29eff73fec588ce5f,PMC,Characterization of the Fecal Bacterial Microbiota of Healthy and Diarrheic Dairy Calves,http://dx.doi.org/10.1111/jvim.14695,PMC5435056,28390070,CC BY-NC,"BACKGROUND: Neonatal diarrhea accounts for more than 50% of total deaths in dairy calves. Few population‐based studies of cattle have investigated how the microbiota is impacted during diarrhea. OBJECTIVES: To characterize the fecal microbiota and predict the functional potential of the microbial communities in healthy and diarrheic calves. METHODS: Fifteen diarrheic calves between the ages of 1 and 30 days and 15 age‐matched healthy control calves were enrolled from 2 dairy farms. The Illumina MiSeq sequencer was used for high‐throughput sequencing of the V4 region of the 16S rRNA gene (Illumina, San Diego, CA). RESULTS: Significant differences in community membership and structure were identified among healthy calves from different farms. Differences in community membership and structure also were identified between healthy and diarrheic calves within each farm. Based on linear discriminant analysis effect size (LEfSe), the genera Bifidobacterium, Megamonas, and a genus of the family Bifidobacteriaceae were associated with health at farm 1, whereas Lachnospiraceae incertae sedis, Dietzia and an unclassified genus of the family Veillonellaceae were significantly associated with health at farm 2. The Phylogenetic Investigation of Communities Reconstruction of Unobserved States (PICRUSt) analysis indicated that diarrheic calves had decreased abundances of genes responsible for metabolism of various vitamins, amino acids, and carbohydrate. CLINICAL RELEVANCE: The fecal microbiota of healthy dairy calves appeared to be farm specific as were the changes observed during diarrhea. The differences in microbiota structure and membership between healthy and diarrheic calves suggest that dysbiosis can occur in diarrheic calves and it is associated with changes in predictive metagenomic function.",2017 Apr 7 May-Jun,"['Gomez, D.E.', 'Arroyo, L.G.', 'Costa, M.C.', 'Viel, L.', 'Weese, J.S.']",J Vet Intern Med,,,False
8b22782e207c5b96f3091e29b01e48ffc80edd03,PMC,Non-invasive ventilation in a pregnancy with severe pneumonia,http://dx.doi.org/10.1016/j.rmcr.2017.05.002,PMC5435593,28560149,CC BY-NC-ND,"INTRODUCTION: Non-invasive ventilation (NIV) is not proven to be effective in treating respiratory failure in severe pneumonia. However, some clinicians nevertheless attempt NIV to indirectly deliver adequate oxygenation and avoid unnecessary endotracheal intubation. CASE PRESENTATION: In this article, we report the case of a 24-year-old woman at 32 weeks' gestation who presented with hypoxemic respiratory failure requiring mechanical ventilation. She was successfully managed by NIV. DISCUSSION: However, NIV must be managed by providers who are trained in mechanical ventilation. This is of the utmost importance in avoiding any delay should the patient's condition worsen and require endotracheal intubation. Moreover, in pregnant women, the severity of illness may progress quickly due to the immunosuppression inherent in these patients. CONCLUSION: Special attention should be given to the choices of invasive ventilation and NIV to manage community acquired pneumonia patients in third trimester.",2017 May 8,"['Mazlan, Mohd Zulfakar', 'Ali, Saedah', 'Zainal Abidin, Huda', 'Mokhtar, Ariffin Marzuki', 'Ab Mukmin, Laila', 'Ayub, Zeti Norfidiyati', 'Nadarajan, Chandran']",Respir Med Case Rep,,,False
d1a63ffc7f247f2e825680e974760a8f73676d3c,PMC,Neutrophil gelatinase-associated lipocalin as a potential novel biomarker for ventilator-associated lung injury,http://dx.doi.org/10.3892/mmr.2017.6442,PMC5436233,28393227,CC BY-NC-ND,"Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein of the lipocalin superfamily and its presence was initially observed in activated neutrophils. It has previously been demonstrated that the expression of NGAL is markedly increased in stimulated epithelia, and is important in the innate immunological response to various pathophysiological conditions, including infection, cancer, inflammation and kidney injury. The present study constructed a ventilator-associated lung injury model in mice. NGAL mRNA and protein expression levels in lung tissue were detected using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. In addition, NGAL protein levels in bronchoalveolar lavage fluid and serum were measured via western blotting. The results of the present study suggested that NGAL expression increased under all mechanical ventilation treatments. The increase was most prominent in the high peak inflation pressure and high-volume mechanical ventilation groups, where there was the greatest extent of lung injury. In addition, NGAL expression increased in a time-dependent manner under high-volume mechanical ventilation, consistent with the degree of lung injury. These findings suggested that NGAL may serve as a potential novel biomarker in ventilator-associated lung injury.",2017 Jun 7,"['Xiao, Rui', 'Chen, Rongchang']",Mol Med Rep,,,True
95e043b6473e5263d1beddfb3f543e27ec7933c4,PMC,A brief historical overview of emerging infectious disease response in China and the need for a One Health approach in future responses,http://dx.doi.org/10.1016/j.onehlt.2016.07.001,PMC5441323,28616482,CC BY-NC-ND,,2016 Jul 9,"['Lu, Jiahai', 'Milinovich, Gabriel J.', 'Hu, Wenbiao']",One Health,,,False
416c18fdc648694ae3865e39b522edb784a12041,PMC,Absence of MERS-CoV antibodies in feral camels in Australia: Implications for the pathogen's origin and spread,http://dx.doi.org/10.1016/j.onehlt.2015.10.003,PMC5441328,28616468,CC BY-NC-ND,"Middle East respiratory syndrome coronavirus (MERS-CoV) infections continue to be a serious emerging disease problem internationally with well over 1000 cases and a major outbreak outside of the Middle East region. While the hypothesis that dromedary camels are the likely major source of MERS-CoV infection in humans is gaining acceptance, conjecture continues over the original natural reservoir host(s) and specifically the role of bats in the emergence of the virus. Dromedary camels were imported to Australia, principally between 1880 and 1907 and have since become a large feral population inhabiting extensive parts of the continent. Here we report that during a focussed surveillance study, no serological evidence was found for the presence of MERS-CoV in the camels in the Australian population. This finding presents various hypotheses about the timing of the emergence and spread of MERS-CoV throughout populations of camels in Africa and Asia, which can be partially resolved by testing sera from camels from the original source region, which we have inferred was mainly northwestern Pakistan. In addition, we identify bat species which overlap (or neighbour) the range of the Australian camel population with a higher likelihood of carrying CoVs of the same lineage as MERS-CoV. Both of these proposed follow-on studies are examples of “proactive surveillance”, a concept that has particular relevance to a One Health approach to emerging zoonotic diseases with a complex epidemiology and aetiology.",2015 Nov 2,"['Crameri, Gary', 'Durr, Peter A.', 'Barr, Jennifer', 'Yu, Meng', 'Graham, Kerryne', 'Williams, Owen J.', 'Kayali, Ghazi', 'Smith, David', 'Peiris, Malik', 'Mackenzie, John S.', 'Wang, Lin-Fa']",One Health,,,False
249d9fd92f43b45e24cdcf2c8e4531ffda88635c,PMC,Absence of MERS-CoV antibodies in feral camels in Australia: Implications for the pathogen's origin and spread,http://dx.doi.org/10.1016/j.onehlt.2015.10.003,PMC5441328,28616468,CC BY-NC-ND,"Middle East respiratory syndrome coronavirus (MERS-CoV) infections continue to be a serious emerging disease problem internationally with well over 1000 cases and a major outbreak outside of the Middle East region. While the hypothesis that dromedary camels are the likely major source of MERS-CoV infection in humans is gaining acceptance, conjecture continues over the original natural reservoir host(s) and specifically the role of bats in the emergence of the virus. Dromedary camels were imported to Australia, principally between 1880 and 1907 and have since become a large feral population inhabiting extensive parts of the continent. Here we report that during a focussed surveillance study, no serological evidence was found for the presence of MERS-CoV in the camels in the Australian population. This finding presents various hypotheses about the timing of the emergence and spread of MERS-CoV throughout populations of camels in Africa and Asia, which can be partially resolved by testing sera from camels from the original source region, which we have inferred was mainly northwestern Pakistan. In addition, we identify bat species which overlap (or neighbour) the range of the Australian camel population with a higher likelihood of carrying CoVs of the same lineage as MERS-CoV. Both of these proposed follow-on studies are examples of “proactive surveillance”, a concept that has particular relevance to a One Health approach to emerging zoonotic diseases with a complex epidemiology and aetiology.",2015 Nov 2,"['Crameri, Gary', 'Durr, Peter A.', 'Barr, Jennifer', 'Yu, Meng', 'Graham, Kerryne', 'Williams, Owen J.', 'Kayali, Ghazi', 'Smith, David', 'Peiris, Malik', 'Mackenzie, John S.', 'Wang, Lin-Fa']",One Health,,,False
b3f8dab7ff123599384b8454a91dea037c2f27e9,PMC,This could be the start of something big—20 years since the identification of bats as the natural host of Hendra virus,http://dx.doi.org/10.1016/j.onehlt.2015.07.001,PMC5441360,28616459,CC BY-NC-ND,"Hendra virus was first described in 1994 in Australia, causally associated with a cluster of fatal equine and human cases at a thoroughbred racing stable in the Brisbane suburb of Hendra. This year marks the twentieth anniversary of the identification of pteropid bats (flying-foxes) as the natural host of the virus, and it is timely to reflect on a pivotal meeting of an eclectic group of scientists in that process. They included animal and public health experts, environmental scientists, veterinary and horse industry representatives, and wildlife experts. The task was to review and prioritise wildlife surveillance seeking the origin of the previously unknown virus. The group determined that the likely reservoir must occur in disparate locations, and be capable of moving between locations, or exist in continuous, overlapping populations spanning multiple locations. Flying-foxes were considered to be a more probable source of the novel virus than birds. Within weeks, antibodies were detected in several species of flying-fox, and the virus was subsequently isolated. While the identification of the natural host of Hendra virus within 18 months of its description was remarkable in itself, a broader legacy followed. In the subsequent years, a suite of zoonotic viruses including Australian bat lyssavirus, Nipah virus, SARS coronavirus, and Ebola and Marburg viruses have been detected in bats. Bats are now the “go to” taxa for novel viruses. History has repeatedly demonstrated that knowledge begets knowledge. This simple notion of bringing a diverse group of people together in an environment of mutual respect reinforced this principle and proves that the sum is often so much more powerful than the parts.",2015 Aug 4,"['Black, Peter', 'Douglas, Ian', 'Field, Hume']",One Health,,,False
cc8ca1ac68f331b8a837e30a0a8e2d13586ef53a,PMC,Periodic global One Health threats update,http://dx.doi.org/10.1016/j.onehlt.2015.11.001,PMC5441380,28616469,CC BY-NC-ND,"Emerging infectious diseases continue to impose unpredictable burdens on global health and economy. Infectious disease surveillance and pandemic preparedness are essential to mitigate the impact of future threats. Global surveillance networks provide unprecedented monitoring data on plant, animal and human infectious diseases. Using such sources, we report on current major One Health threats and update on their epidemiological status.",2015 Dec 4,"['Reperant, Leslie A.', 'MacKenzie, John', 'Osterhaus, Albert D.M.E.']",One Health,,,False
cb6ac0e6f129a47a228c217485d17d091c8c2421,PMC,"Pre-existing immunity against Ad vectors: Humoral, cellular, and innate response, what's important?",http://dx.doi.org/10.4161/hv.29594,PMC5443060,25483662,CC BY-NC,"Pre-existing immunity against human adenovirus (HAd) serotype 5 derived vector in the human population is widespread, thus hampering its clinical use. Various components of the immune system, including neutralizing antibodies (nAbs), Ad specific T cells and type I IFN activated NK cells, contribute to dampening the efficacy of Ad vectors in individuals with pre-existing Ad immunity. In order to circumvent pre-existing immunity to adenovirus, numerous strategies, such as developing alternative Ad serotypes, varying immunization routes and utilizing prime-boost regimens, are under pre-clinical or clinical phases of development. However, these strategies mainly focus on one arm of pre-existing immunity. Selection of alternative serotypes has been largely driven by the absence in the human population of nAbs against them with little attention paid to cross-reactive Ad specific T cells. Conversely, varying the route of immunization appears to mainly rely on avoiding Ad specific tissue-resident T cells. Finally, prime-boost regimens do not actually circumvent pre-existing immunity but instead generate immune responses of sufficient magnitude to confer protection despite pre-existing immunity. Combining the above strategies and thus taking into account all components regulating pre-existing Ad immunity will help further improve the development of Ad vectors for animal and human use.",2014 Nov 1,"['Fausther-Bovendo, Hugues', 'Kobinger, Gary P']",Hum Vaccin Immunother,,,True
751764ca73c84e497075d172d6417ea95c1a7e09,PMC,Community-acquired Pseudomonas aeruginosa-pneumonia in a previously healthy man occupationally exposed to metalworking fluids,http://dx.doi.org/10.4322/acr.2014.026,PMC5444396,28573116,CC BY-NC,"Although the Pseudomonas aeruginosa infection is well known and frequently found in hospitals and nursing care facilities, many cases are also reported outside these boundaries. In general, this pathogen infects debilitated patients either by comorbidities or by any form of immunodeficiency. In cases of respiratory infection, tobacco abuse seems to play an important role as a risk factor. In previously healthy patients, community-acquired pneumonia (CAP) with P. aeruginosa as the etiological agent is extremely rare, and unlike the cases involving immunocompromised or hospitalized patients, the outcome is severe, and is fatal in up to 61.1% of cases. Aerosolized contaminated water or solutions are closely linked to the development of respiratory tract infection. In this setting, metalworking fluids used in factories may be implicated in CAP involving previously healthy people. The authors report the case of a middle-aged man who worked in a metalworking factory and presented a right upper lobar pneumonia with a rapid fatal outcome. P. aeruginosa was cultured from blood and tracheal aspirates. The autopsy findings confirmed a hemorrhagic necrotizing pneumonia with bacteria-invading vasculitis and thrombosis. A culture of the metalworking fluid of the factory was also positive for P. aeruginosa. The pulsed-field gel electrophoresis showed that both strains (blood culture and metalworking fluid) were genetically indistinguishable. The authors highlight the occupational risk for the development of this P. aeruginosa-infection in healthy people.",2014 Sep 30,"['Ferraz de Campos, Fernando Peixoto', 'Felipe-Silva, Aloísio', 'Lopes, Ana Claudia Frota Machado de Melo', 'Passadore, Lilian Ferri', 'Guida, Stella Maria', 'Balabakis, Angélica Jean', 'Martines, João Augusto dos Santos']",Autops Case Rep,,,True
3e43a3250148f30593f56be70799a2186143581c,PMC,In this issue,,PMC5447183,,CC BY-NC-SA,,2017 Apr,,Saudi Med J,,,False
86f8e5cdfe075d029d603b36ce6f43a5ed86a8a5,PMC,Middle East respiratory syndrome in children: Dental considerations,http://dx.doi.org/10.15537/smj.2017.4.15777,PMC5447184,28397938,CC BY-NC-SA,"As of January 2016, 1,633 laboratory-confirmed cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection and 587 MERS-related deaths have been reported by the World Health Organization globally. Middle East Respiratory Syndrome Coronavirus may occur sporadically in communities or may be transmitted within families or hospitals. The number of confirmed MERS-CoV cases among healthcare workers has been increasing. Middle East Respiratory Syndrome Coronavirus may also spread through aerosols generated during various dental treatments, resulting in transmission between patients and dentists. As MERS-CoV cases have also been reported among children, pediatric dentists are at risk of MERS-CoV infection. This review discusses MERS-CoV infection in children and healthcare workers, especially pediatric dentists, and considerations pertaining to pediatric dentistry. Although no cases of MERS-CoV transmission between a patient and a dentist have yet been reported, the risk of MERS-CoV transmission from an infected patient may be high due to the unique work environment of dentists (aerosol generation).",2017 Apr,"Al-Sehaibany, Fares S.",Saudi Med J,,,True
98364308fd44bb4fb686480fb10c968e918715f1,PMC,Impacts of triamcinolone acetonide on femoral head chondrocytic structures in lumbosacral plexus block,http://dx.doi.org/10.1016/j.jsps.2017.04.012,PMC5447409,28579881,CC BY-NC-ND,"Objective: To investigate impacts of triamcinolone acetonide (TRI) on femoral head chondrocytic (FHC) structures when used for lumbosacral plexus block (LPB). Methods: A total of 32 6-month-old New Zealand white rabbits were selected (averagely weighing 2.75–3.25 kg) and added TRI into nerve block solution for LPB. The rabbit were randomly divided into four groups: group A1: 2.5 ml × 2 times, group A2 2.5 ml × 4 times, group B1 5 ml × 2 times, and group B2 5 ml × 4 times; the time interval among the injection was 5 days, and the structural changes of FHC were the observed using 50/100/200 light microscope; the modified Mankin pathological scoring was also performed for the evaluation. Results: There exhibited significant microscopic changes of FHC structures between the rabbits performed LPB and the normal rabbits, among which group B2 exhibited the most serious FHC damages, and the Mankin pathological score in group B2 was much higher than those in the other three groups, and the scores of the experimental group were higher than the control group. Conclusions: The addition of TRI in LPB can damage the FHC structures, and large-dose (5 ml/once) and long-course (four times) will result in more serious injuries.",2017 May 21,"['Wang, Dashou', 'Chen, Qian', 'Cai, Fengjun', 'Pan, Qi', 'Li, Xuesong', 'Wu, Qianming', 'Gan, Yong', 'Meng, Fei', 'Luo, Ping']",Saudi Pharm J,,,False
81a11c6680ce725535704809655d945cd1d4a088,PMC,Coordination among tertiary base pairs results in an efficient frameshift-stimulating RNA pseudoknot,http://dx.doi.org/10.1093/nar/gkx134,PMC5449628,28334864,CC BY-NC,"Frameshifting is an essential process that regulates protein synthesis in many viruses. The ribosome may slip backward when encountering a frameshift motif on the messenger RNA, which usually contains a pseudoknot structure involving tertiary base pair interactions. Due to the lack of detailed molecular explanations, previous studies investigating which features of the pseudoknot are important to stimulate frameshifting have presented diverse conclusions. Here we constructed a bimolecular pseudoknot to dissect the interior tertiary base pairs and used single-molecule approaches to assess the structure targeted by ribosomes. We found that the first ribosome target stem was resistant to unwinding when the neighboring loop was confined along the stem; such constrained conformation was dependent on the presence of consecutive adenosines in this loop. Mutations that disrupted the distal base triples abolished all remaining tertiary base pairs. Changes in frameshifting efficiency correlated with the stem unwinding resistance. Our results demonstrate that various tertiary base pairs are coordinated inside a highly efficient frameshift-stimulating RNA pseudoknot and suggest a mechanism by which mechanical resistance of the pseudoknot may persistently act on translocating ribosomes.",2017 Jun 2,"['Chen, Yu-Ting', 'Chang, Kai-Chun', 'Hu, Hao-Teng', 'Chen, Yi-Lan', 'Lin, You-Hsin', 'Hsu, Chiung-Fang', 'Chang, Cheng-Fu', 'Chang, Kung-Yao', 'Wen, Jin-Der']",Nucleic Acids Res,,,True
42d6a33f03497257ad765977dd53d0c4709e5e77,PMC,Coordination among tertiary base pairs results in an efficient frameshift-stimulating RNA pseudoknot,http://dx.doi.org/10.1093/nar/gkx134,PMC5449628,28334864,CC BY-NC,"Frameshifting is an essential process that regulates protein synthesis in many viruses. The ribosome may slip backward when encountering a frameshift motif on the messenger RNA, which usually contains a pseudoknot structure involving tertiary base pair interactions. Due to the lack of detailed molecular explanations, previous studies investigating which features of the pseudoknot are important to stimulate frameshifting have presented diverse conclusions. Here we constructed a bimolecular pseudoknot to dissect the interior tertiary base pairs and used single-molecule approaches to assess the structure targeted by ribosomes. We found that the first ribosome target stem was resistant to unwinding when the neighboring loop was confined along the stem; such constrained conformation was dependent on the presence of consecutive adenosines in this loop. Mutations that disrupted the distal base triples abolished all remaining tertiary base pairs. Changes in frameshifting efficiency correlated with the stem unwinding resistance. Our results demonstrate that various tertiary base pairs are coordinated inside a highly efficient frameshift-stimulating RNA pseudoknot and suggest a mechanism by which mechanical resistance of the pseudoknot may persistently act on translocating ribosomes.",2017 Jun 2,"['Chen, Yu-Ting', 'Chang, Kai-Chun', 'Hu, Hao-Teng', 'Chen, Yi-Lan', 'Lin, You-Hsin', 'Hsu, Chiung-Fang', 'Chang, Cheng-Fu', 'Chang, Kung-Yao', 'Wen, Jin-Der']",Nucleic Acids Res,,,True
2e8fcc213e690efe461306e2bc37eec6c4151315,PMC,Human rhinovirus detection in the lower respiratory tract of hematopoietic cell transplant recipients: association with mortality,http://dx.doi.org/10.3324/haematol.2016.153767,PMC5451345,28183847,CC BY-NC,"Human rhinoviruses are the most common respiratory viruses detected in patients after hematopoietic cell transplantation. Although rhinovirus appears to occasionally cause severe lower respiratory tract infection in immunocompromised patients, the clinical significance of rhinovirus detection in the lower respiratory tract remains unknown. We evaluated 697 recipients transplanted between 1993 and 2015 with rhinovirus in respiratory samples. As comparative cohorts, 273 recipients with lower respiratory tract infection caused by respiratory syncytial virus (N=117), parainfluenza virus (N=120), or influenza (N=36) were analyzed. Factors associated with mortality were analyzed using Cox proportional hazard models. Among 569 subjects with rhinovirus upper respiratory tract infection and 128 subjects with rhinovirus lower respiratory tract infection, probabilities of overall mortality at 90 days were 6% and 41%, respectively (P<0.001). The survival rate after lower respiratory tract infection was not affected by the presence of co-pathogens (55% in patients with co-pathogens, 64% in patients without, P=0.34). Low monocyte count (P=0.027), oxygen use (P=0.015), and steroid dose greater than 1 mg/kg/day (P=0.003) before diagnosis were significantly associated with mortality among patients with lower respiratory tract infection in multivariable analysis. Mortality after rhinovirus lower respiratory tract infection was similar to that after lower respiratory tract infection by respiratory syncytial virus, parainfluenza virus or influenza in an adjusted model. In summary, transplant recipients with rhinovirus detection in the lower respiratory tract had high mortality rates comparable to viral pneumonia associated with other well-established respiratory viruses. Our data suggest rhinovirus can contribute to severe pulmonary disease in immunocompromised hosts.",2017 Jun,"['Seo, Sachiko', 'Waghmare, Alpana', 'Scott, Emily M', 'Xie, Hu', 'Kuypers, Jane M', 'Hackman, Robert C.', 'Campbell, Angela P.', 'Choi, Su-Mi', 'Leisenring, Wendy M.', 'Jerome, Keith R.', 'Englund, Janet A.', 'Boeckh, Michael']",Haematologica,,,True
205ca26c0033e59a64180fcb182ec95854e67bb6,PMC,Human rhinovirus detection in the lower respiratory tract of hematopoietic cell transplant recipients: association with mortality,http://dx.doi.org/10.3324/haematol.2016.153767,PMC5451345,28183847,CC BY-NC,"Human rhinoviruses are the most common respiratory viruses detected in patients after hematopoietic cell transplantation. Although rhinovirus appears to occasionally cause severe lower respiratory tract infection in immunocompromised patients, the clinical significance of rhinovirus detection in the lower respiratory tract remains unknown. We evaluated 697 recipients transplanted between 1993 and 2015 with rhinovirus in respiratory samples. As comparative cohorts, 273 recipients with lower respiratory tract infection caused by respiratory syncytial virus (N=117), parainfluenza virus (N=120), or influenza (N=36) were analyzed. Factors associated with mortality were analyzed using Cox proportional hazard models. Among 569 subjects with rhinovirus upper respiratory tract infection and 128 subjects with rhinovirus lower respiratory tract infection, probabilities of overall mortality at 90 days were 6% and 41%, respectively (P<0.001). The survival rate after lower respiratory tract infection was not affected by the presence of co-pathogens (55% in patients with co-pathogens, 64% in patients without, P=0.34). Low monocyte count (P=0.027), oxygen use (P=0.015), and steroid dose greater than 1 mg/kg/day (P=0.003) before diagnosis were significantly associated with mortality among patients with lower respiratory tract infection in multivariable analysis. Mortality after rhinovirus lower respiratory tract infection was similar to that after lower respiratory tract infection by respiratory syncytial virus, parainfluenza virus or influenza in an adjusted model. In summary, transplant recipients with rhinovirus detection in the lower respiratory tract had high mortality rates comparable to viral pneumonia associated with other well-established respiratory viruses. Our data suggest rhinovirus can contribute to severe pulmonary disease in immunocompromised hosts.",2017 Jun,"['Seo, Sachiko', 'Waghmare, Alpana', 'Scott, Emily M', 'Xie, Hu', 'Kuypers, Jane M', 'Hackman, Robert C.', 'Campbell, Angela P.', 'Choi, Su-Mi', 'Leisenring, Wendy M.', 'Jerome, Keith R.', 'Englund, Janet A.', 'Boeckh, Michael']",Haematologica,,,False
e08f46a64fec2a7fb30a56519461a586e606a5af,PMC,Human rhinovirus detection in the lower respiratory tract of hematopoietic cell transplant recipients: association with mortality,http://dx.doi.org/10.3324/haematol.2016.153767,PMC5451345,28183847,CC BY-NC,"Human rhinoviruses are the most common respiratory viruses detected in patients after hematopoietic cell transplantation. Although rhinovirus appears to occasionally cause severe lower respiratory tract infection in immunocompromised patients, the clinical significance of rhinovirus detection in the lower respiratory tract remains unknown. We evaluated 697 recipients transplanted between 1993 and 2015 with rhinovirus in respiratory samples. As comparative cohorts, 273 recipients with lower respiratory tract infection caused by respiratory syncytial virus (N=117), parainfluenza virus (N=120), or influenza (N=36) were analyzed. Factors associated with mortality were analyzed using Cox proportional hazard models. Among 569 subjects with rhinovirus upper respiratory tract infection and 128 subjects with rhinovirus lower respiratory tract infection, probabilities of overall mortality at 90 days were 6% and 41%, respectively (P<0.001). The survival rate after lower respiratory tract infection was not affected by the presence of co-pathogens (55% in patients with co-pathogens, 64% in patients without, P=0.34). Low monocyte count (P=0.027), oxygen use (P=0.015), and steroid dose greater than 1 mg/kg/day (P=0.003) before diagnosis were significantly associated with mortality among patients with lower respiratory tract infection in multivariable analysis. Mortality after rhinovirus lower respiratory tract infection was similar to that after lower respiratory tract infection by respiratory syncytial virus, parainfluenza virus or influenza in an adjusted model. In summary, transplant recipients with rhinovirus detection in the lower respiratory tract had high mortality rates comparable to viral pneumonia associated with other well-established respiratory viruses. Our data suggest rhinovirus can contribute to severe pulmonary disease in immunocompromised hosts.",2017 Jun,"['Seo, Sachiko', 'Waghmare, Alpana', 'Scott, Emily M', 'Xie, Hu', 'Kuypers, Jane M', 'Hackman, Robert C.', 'Campbell, Angela P.', 'Choi, Su-Mi', 'Leisenring, Wendy M.', 'Jerome, Keith R.', 'Englund, Janet A.', 'Boeckh, Michael']",Haematologica,,,False
f523909ff52d8a6b9e7ddeb44c7d10ff9adf366c,PMC,Searching for animal models and potential target species for emerging pathogens: Experience gained from Middle East respiratory syndrome (MERS) coronavirus,http://dx.doi.org/10.1016/j.onehlt.2017.03.001,PMC5454147,28616501,CC BY-NC-ND,"Emerging and re-emerging pathogens represent a substantial threat to public health, as demonstrated with numerous outbreaks over the past years, including the 2013–2016 outbreak of Ebola virus in western Africa. Coronaviruses are also a threat for humans, as evidenced in 2002/2003 with infection by the severe acute respiratory syndrome coronavirus (SARS-CoV), which caused more than 8000 human infections with 10% fatality rate in 37 countries. Ten years later, a novel human coronavirus (Middle East respiratory syndrome coronavirus, MERS-CoV), associated with severe pneumonia, arose in the Kingdom of Saudi Arabia. Until December 2016, MERS has accounted for more than 1800 cases and 35% fatality rate. Finding an animal model of disease is key to develop vaccines or antivirals against such emerging pathogens and to understand its pathogenesis. Knowledge of the potential role of domestic livestock and other animal species in the transmission of pathogens is of importance to understand the epidemiology of the disease. Little is known about MERS-CoV animal host range. In this paper, experimental data on potential hosts for MERS-CoV is reviewed. Advantages and limitations of different animal models are evaluated in relation to viral pathogenesis and transmission studies. Finally, the relevance of potential new target species is discussed.",2017 Mar 3,"['Vergara-Alert, Júlia', 'Vidal, Enric', 'Bensaid, Albert', 'Segalés, Joaquim']",One Health,,,False
496c9b4e424bc052895fd0c9446e14f565dcaae5,PMC,MERS-coronavirus: From discovery to intervention,http://dx.doi.org/10.1016/j.onehlt.2016.12.001,PMC5454172,28616497,CC BY-NC-ND,"Middle East respiratory syndrome coronavirus (MERS-CoV) still causes outbreaks despite public awareness and implementation of health care measures, such as rapid viral diagnosis and patient quarantine. Here we describe the current epidemiological picture of MERS-CoV, focusing on humans and animals affected by this virus and propose specific intervention strategies that would be appropriate to control MERS-CoV. One-third of MERS-CoV patients develop severe lower respiratory tract infection and succumb to a fatal outcome; these patients would require effective therapeutic antiviral therapy. Because of the lack of such intervention strategies, supportive care is the best that can be offered at the moment. Limiting viral spread from symptomatic human cases to health care workers and family members, on the other hand, could be achieved through prophylactic administration of MERS-CoV neutralizing antibodies and vaccines. To ultimately prevent spread of the virus into the human population, however, vaccination of dromedary camels – currently the only confirmed animal host for MERS-CoV – may be the best option to achieve a sustained drop in human MERS cases in time. In the end, a One Health approach combining all these different efforts is needed to tackle this zoonotic outbreak.",2016 Dec 23,"['Widagdo, W.', 'Okba, Nisreen M.A.', 'Stalin Raj, V.', 'Haagmans, Bart L.']",One Health,,,False
00676f1131e03ca8defe523e79bc1635cc933909,PMC,Dromedary camels in northern Mali have high seropositivity to MERS-CoV,http://dx.doi.org/10.1016/j.onehlt.2017.03.003,PMC5454179,28616502,CC BY-NC-ND,A high percentage (up to 90%) of dromedary camels in the Middle East as well as eastern and central Africa have antibodies to Middle East respiratory syndrome coronavirus (MERS-CoV). Here we report comparably high positivity of MERS-CoV antibodies in dromedary camels from northern Mali. This extends the range of MERS-CoV further west in Africa than reported to date and cautions that MERS-CoV should be considered in cases of severe respiratory disease in the region.,2017 Mar 10,"['Falzarano, Darryl', 'Kamissoko, Badian', 'de Wit, Emmie', 'Maïga, Ousmane', 'Cronin, Jacqueline', 'Samaké, Kassim', 'Traoré, Abdalah', 'Milne-Price, Shauna', 'Munster, Vincent J.', 'Sogoba, Nafomon', 'Niang, Mamadou', 'Safronetz, David', 'Feldmann, Heinz']",One Health,,,False
05fbb0078e14eea85ecbf6904ecef2380d034a10,PMC,Zoos and public health: A partnership on the One Health frontier,http://dx.doi.org/10.1016/j.onehlt.2016.11.003,PMC5454182,28616495,CC BY-NC-ND,"Today, accredited zoos are not just places for entertainment, they are actively involved in research for conservation and health. During recent decades in which the challenges for biodiversity conservation and public health have escalated, zoos have made significant changes to address these difficulties. Zoos increasingly have four key areas of focus: education, recreation, conservation, and research. These key areas are important in addressing an interrelated global conservation (i.e. habitat and wildlife loss) and public health crisis. Zoo and public health professionals working together within a One Health framework represent a powerful alliance to address current and future conservation and public health problems around the world. For researchers, practitioners, and students, the collaboration between zoos and public health institutions offers the opportunity to both teach and operationalize this transdisciplinary approach. Using examples from our programs, we give a template for moving forward with collaborative initiatives and sustainable solutions involving partners in both zoos and public health institutions. We provide examples of cooperative programs and suggest a model for consideration in the development of further activities in this area.",2016 Nov 23,"['Robinette, C.', 'Saffran, L.', 'Ruple, A.', 'Deem, S.L.']",One Health,,,False
2029878b827294f1639d73575783c79c72007c40,PMC,A framework for One Health research,http://dx.doi.org/10.1016/j.onehlt.2017.03.004,PMC5454183,28616503,CC BY-NC-ND,"The need for multidisciplinary research to address today's complex health and environmental challenges has never been greater. The One Health (OH) approach to research ensures that human, animal, and environmental health questions are evaluated in an integrated and holistic manner to provide a more comprehensive understanding of the problem and potential solutions than would be possible with siloed approaches. However, the OH approach is complex, and there is limited guidance available for investigators regarding the practical design and implementation of OH research. In this paper we provide a framework to guide researchers through conceptualizing and planning an OH study. We discuss key steps in designing an OH study, including conceptualization of hypotheses and study aims, identification of collaborators for a multi-disciplinary research team, study design options, data sources and collection methods, and analytical methods. We illustrate these concepts through the presentation of a case study of health impacts associated with land application of biosolids. Finally, we discuss opportunities for applying an OH approach to identify solutions to current global health issues, and the need for cross-disciplinary funding sources to foster an OH approach to research.",2017 Mar 24,"['Lebov, J.', 'Grieger, K.', 'Womack, D.', 'Zaccaro, D.', 'Whitehead, N.', 'Kowalcyk, B.', 'MacDonald, P.D.M.']",One Health,,,False
a3e2f4a9e9c1bc50381ef0161f062bb6f925b7be,PMC,The Usefulness of Platelet-derived Microparticle as Biomarker of Antiplatelet Therapy in Kawasaki Disease,http://dx.doi.org/10.3346/jkms.2017.32.7.1147,PMC5461319,28581272,CC BY-NC,"Little is known about platelet dynamics and the effect of antiplatelet therapy in Kawasaki disease (KD). This study sought to define platelet activation dynamics in KD patients by assaying platelet-derived microparticles (PDMPs). We measured plasma PDMPs levels in 46 patients with KD using an enzyme-linked immunosorbent assay (ELISA). Blood samples were collected before, at 2–5 days, and 9–15 days after intravenous immunoglobulin (IVIG) infusion, 2 months and 4–5 months after the onset of KD. We measured PDMP levels in 23 febrile and 10 afebrile control patients. In the acute phase of KD patients, PDMP levels increased significantly after IVIG treatment (12.04 ± 5.58 nmol before IVIG infusion vs. 19.81 ± 13.21 nmol at 2–5 days after IVIG infusion, P = 0.006). PDMP levels were negatively correlated with age and positively correlated with procalcitonin levels in the acute phase of KD. No significant difference was found in PDMP levels between KD patients with and without coronary artery lesion (CAL). Elevated PDMP levels after IVIG therapy significantly decreased below the pre-IVIG level in subacute phase (19.81 ± 13.21 nmol at 2–5 days after IVIG infusion vs. 8.33 ± 2.02 nmol at 9–15 days after IVIG infusion, P < 0.001), and PDMP levels stayed below the pre-IVIG level in the convalescent phase, during which antiplatelet therapy was given. However, PDMP levels rebounded after discontinuing aspirin in 17 patients. In conclusion, enhanced platelet activation was noted before treatment of KD and peaked immediately after IVIG treatment. Recurrent rising of PDMP levels was observed after discontinuing aspirin, although there were no significant differences between the PDMP levels at 2 months after the onset of KD and those at 4–5 months after the onset of the disease.",2017 Jul 26,"['Kim, Hyun Jung', 'Choi, Eun-Hye', 'Lim, Yeon Jung', 'Kil, Hong Ryang']",J Korean Med Sci,,,True
4ca26be0493fc360519e7586ec0392760846d662,PMC,Spread of Middle East Respiratory Coronavirus: Genetic versus Epidemiological Data,http://dx.doi.org/10.5210/ojphi.v9i1.7581,PMC5462161,,CC BY-NC,,2017 May 1,"['Janies, Daniel A.', 'Ford, Colby', 'Damodaran, Lambodhar', 'Witter, Zachary']",Online J Public Health Inform,,,True
b9462a00480f4a8e69d04678b4cff8a4bb7a7bcb,PMC,Interpreting specific and general respiratory indicators in syndromic surveillance,http://dx.doi.org/10.5210/ojphi.v9i1.7597,PMC5462175,,CC BY-NC,,2017 May 1,"['Morbey, Roger', 'Elliot, Alex J.', 'Zambon, Maria', 'Pebody, Richard', 'Smith, Gillian E.']",Online J Public Health Inform,,,True
c37f596934a7944a47229af9491eaeae4f595528,PMC,"Analysis of Daily Enhanced Syndromic Surveillance in Hillsborough County, FL, 2015",http://dx.doi.org/10.5210/ojphi.v9i1.7675,PMC5462247,,CC BY-NC,,2017 May 1,"['Clark, Charles R.', 'Wiese, Michael']",Online J Public Health Inform,,,False
049cf5f0e55a0f6b472630b01aff93cffffb0ece,PMC,"MERS PUI Surveillance and Restrospective Identification in ESSENCE-FL, 2013-2015",http://dx.doi.org/10.5210/ojphi.v9i1.7696,PMC5462267,,CC BY-NC,,2017 May 1,"['Munroe, Julia G.', 'Straver, Rachael', 'Rubino, Heather', 'Pritchard, Scott', 'Atrubin, David', 'Hamilton, Janet J.']",Online J Public Health Inform,,,False
a38e42b1f6af103e0fca657462dc516ad51cf7e9,PMC,"Human–livestock contacts and their relationship to transmission of zoonotic pathogens, a systematic review of literature",http://dx.doi.org/10.1016/j.onehlt.2016.03.001,PMC5462650,28616478,CC BY-NC-ND,"BACKGROUND: Micro-organisms transmitted from vertebrate animals – including livestock – to humans account for an estimated 60% of human pathogens. Micro-organisms can be transmitted through inhalation, ingestion, via conjunctiva or physical contact. Close contact with animals is crucial for transmission. The role of intensity and type of contact patterns between livestock and humans for disease transmission is poorly understood. In this systematic review we aimed to summarise current knowledge regarding patterns of human–livestock contacts and their role in micro-organism transmission. METHODS: We included peer-reviewed publications published between 1996 and 2014 in our systematic review if they reported on human–livestock contacts, human cases of livestock-related zoonotic diseases or serological epidemiology of zoonotic diseases in human samples. We extracted any information pertaining the type and intensity of human–livestock contacts and associated zoonoses. RESULTS: 1522 papers were identified, 75 were included: 7 reported on incidental zoonoses after brief animal–human contacts (e.g. farm visits), 10 on environmental exposures and 15 on zoonoses in developing countries where backyard livestock keeping is still customary. 43 studies reported zoonotic risks in different occupations. Occupations at risk included veterinarians, culling personnel, slaughterhouse workers and farmers. For culling personnel, more hours exposed to livestock resulted in more frequent occurrence of transmission. Slaughterhouse workers in contact with live animals were more often positive for zoonotic micro-organisms compared to co-workers only exposed to carcasses. Overall, little information was available about the actual mode of micro-organism transmission. CONCLUSIONS: Little is known about the intensity and type of contact patterns between livestock and humans that result in micro-organism transmission. Studies performed in occupational settings provide some, but limited evidence of exposure response-like relationships for livestock–human contact and micro-organism transmission. Better understanding of contact patterns driving micro-organism transmission from animals to humans is needed to provide options for prevention and thus deserves more attention.",2016 Apr 6,"['Klous, Gijs', 'Huss, Anke', 'Heederik, Dick J.J.', 'Coutinho, Roel A.']",One Health,,,False
2c0813f50214197ccbeae857bb05217ade8aae82,PMC,"Human Coronavirus-HKU1 Infection Among Adults in Cleveland, Ohio",http://dx.doi.org/10.1093/ofid/ofx052,PMC5466428,28616442,CC BY-NC-ND,"BACKGROUND. Human coronaviruses (CoV) have been long recognized as a common cause of respiratory tract disease including severe respiratory tract illness. Coronavirus-HKU1 has been described predominantly among children less than 5 years of age in the United States with few studies characterizing the disease spectrum among adults. METHODS. Nasopharyngeal specimens of patients with respiratory symptoms were analyzed for CoV-HKU1 by NxTAG Respiratory Pathogen Panel multiplex assay from February 7, 2016 to April 30, 2016. Epidemiologic, clinical, and laboratory data were collected on adults (patients >18 years) whose samples screened positive. RESULTS. Of 832 adult respiratory specimens screened, 13 (1.6%) cases of CoV-HKU1 were identified. Adults age ranged between 23 and 75 years and 6 (46%) were males. All of whom had 1 or more respiratory symptoms, and 5 (38%) also reported 1 or more gastrointestinal symptoms. Eleven (85%) reported history of smoking and 5 (38%) used inhaled steroids. Seven (54%) required hospitalization, 5 (71%) of these needed supplemental oxygen, and 2 (29%) were admitted to intensive care. Median length of hospitalization was 5 days. Eight (62%) received antibiotics despite identification of CoV-HKU1. Infectious work-up in 1 patient who died did not reveal any other pathogen. In 2 (15%) CoV-HKU1-positive adults, the only viral coinfection detected was influenza A. CONCLUSIONS. Coronavirus-HKU1 accounted for 1.6% of adult respiratory infections and should be considered in differential diagnosis of severe respiratory illnesses among adults.",2017 Mar 25,"['Kanwar, Anubhav', 'Selvaraju, Suresh', 'Esper, Frank']",Open Forum Infect Dis,,,True
ee254e8dd94c816c9b5cd80c56b4b7e07eb5aa03,PMC,Global patterns in coronavirus diversity,http://dx.doi.org/10.1093/ve/vex012,PMC5467638,28630747,CC BY-NC,"Since the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrom Coronavirus (MERS-CoV) it has become increasingly clear that bats are important reservoirs of CoVs. Despite this, only 6% of all CoV sequences in GenBank are from bats. The remaining 94% largely consist of known pathogens of public health or agricultural significance, indicating that current research effort is heavily biased towards describing known diseases rather than the ‘pre-emergent’ diversity in bats. Our study addresses this critical gap, and focuses on resource poor countries where the risk of zoonotic emergence is believed to be highest. We surveyed the diversity of CoVs in multiple host taxa from twenty countries to explore the factors driving viral diversity at a global scale. We identified sequences representing 100 discrete phylogenetic clusters, ninety-one of which were found in bats, and used ecological and epidemiologic analyses to show that patterns of CoV diversity correlate with those of bat diversity. This cements bats as the major evolutionary reservoirs and ecological drivers of CoV diversity. Co-phylogenetic reconciliation analysis was also used to show that host switching has contributed to CoV evolution, and a preliminary analysis suggests that regional variation exists in the dynamics of this process. Overall our study represents a model for exploring global viral diversity and advances our fundamental understanding of CoV biodiversity and the potential risk factors associated with zoonotic emergence.",2017 Jun 12,"['Anthony, Simon J.', 'Johnson, Christine K.', 'Greig, Denise J.', 'Kramer, Sarah', 'Che, Xiaoyu', 'Wells, Heather', 'Hicks, Allison L.', 'Joly, Damien O.', 'Wolfe, Nathan D.', 'Daszak, Peter', 'Karesh, William', 'Lipkin, W. I.', 'Morse, Stephen S.', None, 'Mazet, Jonna A. K.', 'Goldstein, Tracey']",Virus Evol,,,True
c2d4efc02a8e37fb93eafe7ddb9eff42e0c600b2,PMC,Mechanisms of Accountability for the Realization of the Right to Health in China,,PMC5473057,28630560,CC BY-NC,"China ratified the International Covenant on Economic, Social and Cultural Rights in 2001. It thus bears obligations under Article 12 of the covenant to take appropriate measures at the domestic level to realize the right to health in China. Accountability is an important component of the right to health. This article examines whether the Western concept of accountability, recently imported into China, has the potential to improve the protection of the right to health within China’s existing political, legal, and cultural framework. In so doing, it reviews current Chinese institutional mechanisms and considers the use of less formal mechanisms by which duty-bearers might be held accountable in China. More specifically, this article provides an overview of a range of health-related accountability mechanisms, including judicial, political, administrative, professional, and social accountability arrangements. It concludes that although there is the basis of an accountability framework for the right to health in China, the effective operation of accountability mechanisms is hindered by longstanding cultural and political barriers.",2017 Jun,"['Qiu, Shengnan', 'Macnaughton, Gillian']",Health Hum Rights,,,True
8fe6e12ec1f61c111c3ca33189fcc0ec90c03803,PMC,Vaccinations against respiratory infections in Arabian Gulf countries: Barriers and motivators,http://dx.doi.org/10.12998/wjcc.v5.i6.212,PMC5480069,28685134,CC BY-NC,"AIM: To study the uptake, barriers and motivators of influenza, pneumococcal, meningococcal and pertussis vaccines among members of public in Arabian Gulf countries. METHODS: A cross-sectional survey among the Gulf Cooperation Council (GCC) countries’ residents. Data collected electronically through a smartphone app. The survey variables aimed to investigate the respondents’ awareness about vaccines against influenza, pneumococcal, meningococcal and pertussis infections. Collected data concerning the respondents’ socio-demographic characteristics, their perception toward vaccine uptake and the factors that motivate or demotivate them from taking influenza vaccine. The data were analysed statistically using the SPSS v.23.0. Differences in the characteristics of users from different countries were quantified through bivariate analysis. Other important variables and controlling factors were studied using logistic regression. RESULTS: A total of 1812 respondents participated in the study. Their mean age was 27 years, 82% were male and 24% had ≥ 1 chronic diseases. The overall uptake of influenza vaccine was 17% (21% among “at risk” people) and ranged from 15% in Saudi Arabia to 24% in Qatar. Doctor’s advice (23%) and a perception of having low body immunity (21%) were the main cited reasons for being vaccinated, whereas unawareness about the vaccine (43%) was the main barrier. The overall uptake of pneumococcal vaccine in the preceding three years was 22% (25% among “at risk” individuals) and ranged from 0% in Bahrain to 79% in Kuwait. The overall uptake of pertussis vaccine was 16% (31% among “vulnerable” people), and ranged from 7% in Saudi Arabia to 75% in Oman. The overall uptake of meningococcal vaccine was 20% (29% among the “at risk” people) and ranged from 3% in Oman to 50% in Bahrain. CONCLUSION: The vaccination uptake across GCC countries is suboptimal and varies widely across the countries. Further research is needed to unearth the reasons and formulate action plan.",2017 Jun 16,"['Alqahtani, Amani S', 'Bondagji, Daniah M', 'Alshehari, Abdullah A', 'Basyouni, Mada H', 'Alhawassi, Tariq M', 'BinDhim, Nasser F', 'Rashid, Harunor']",World J Clin Cases,,,True
f90706bbb06cb2fa2992200bddfa2a3305f52b67,PMC,"Etiology, Seasonality, and Clinical Features of Viral Respiratory Tract Infections in Children Hospitalized With Acute Bronchiolitis: A Single-Center Study",http://dx.doi.org/10.1177/2333794X17714378,PMC5484425,28680946,CC BY-NC,"The purpose of this study was to evaluate the viral frequency, seasonality, and clinical and demographic features of patients hospitalized with acute bronchiolitis. A cross-sectional, descriptive study was performed in 316 infants younger than 2 years of age who were hospitalized for acute viral bronchiolitis. Respiratory tract infection agents were investigated with polymerase chain reaction (PCR). A total of 316 infants were included in this study. Of the 316 infants, at least one respiratory tract pathogen was detected in 75% (237/316). Respiratory syncytial virus (RSV) was the most common virus identified in 127 infants (40.1%) followed by rhinovirus (n = 78, 24.6%). In this study, where viral agents were determined via PCR in patients who were followed-up due to the diagnosis of acute bronchiolitis, RSV was detected as the most common agent, as in other studies. In almost half of the RSV-positive patients, RSV was accompanied by a second or third agent.",2017 Jun 22,"['Gökçe, Şule', 'Kurugöl, Zafer', 'Koturoğlu, Güldane', 'Çiçek, Candan', 'Aslan, Aslı']",Glob Pediatr Health,,,True
37f31338fc1447eb78c6b17f93e700f77728e25d,PMC,"Virtual screening for potential inhibitors of Mcl-1 conformations sampled by normal modes, molecular dynamics, and nuclear magnetic resonance",http://dx.doi.org/10.2147/DDDT.S133127,PMC5484510,28684899,CC BY-NC,"Myeloid cell leukemia-1 (Mcl-1) is often overexpressed in human cancer and is an important target for developing antineoplastic drugs. In this study, a data set containing 2.3 million lead-like molecules and a data set of all the US Food and Drug Administration (FDA)-approved drugs are virtually screened for potential Mcl-1 ligands using Protein Data Bank (PDB) ID 2MHS. The potential Mcl-1 ligands are evaluated and computationally docked on to three conformation ensembles generated by normal mode analysis (NMA), molecular dynamics (MD), and nuclear magnetic resonance (NMR), respectively. The evaluated potential Mcl-1 ligands are then compared with their clinical use. Remarkably, half of the top 30 potential drugs are used clinically to treat cancer, thus partially validating our virtual screen. The partial validation also favors the idea that the other half of the top 30 potential drugs could be used in the treatment of cancer. The normal mode-, MD-, and NMR-based conformation greatly expand the conformational sampling used herein for in silico identification of potential Mcl-1 inhibitors.",2017 Jun 19,"['Glantz-Gashai, Yitav', 'Meirson, Tomer', 'Reuveni, Eli', 'Samson, Abraham O']",Drug Des Devel Ther,,,True
9d12f3a201435c9d24dc9b356283edf8bd3a234d,PMC,Exacerbation of Japanese Encephalitis by CD11c(hi) Dendritic Cell Ablation Is Associated with an Imbalance in Regulatory Foxp3(+) and IL-17(+)CD4(+) Th17 Cells and in Ly-6C(hi) and Ly-6C(lo) Monocytes,http://dx.doi.org/10.4110/in.2017.17.3.192,PMC5484650,28680381,CC BY-NC,"Japanese encephalitis (JE) is neuroinflammation characterized by uncontrolled infiltration of peripheral leukocytes into the central nervous system (CNS). We previously demonstrated exacerbation of JE following CD11c(hi) dendritic cell (DC) ablation in CD11c-DTR transgenic mice. Moreover, CD11c(hi) DC ablation led to abnormal differentiation of CD11b(+)Ly-6C(hi) monocytes and enhanced permeability of the blood-brain barrier (BBB), resulting in promoting the progression of JE. Here, we examined changes in lymphoid and myeloid-derived leukocyte subpopulations associated with pro- and anti-inflammation during JE progression. The analyses of this study focused on regulatory CD4(+)Foxp3(+) regulatory T cells (Tregs), IL-17(+)CD4(+) Th17 cells, and CD11b(+)Ly-6C(hi) and Ly-6C(lo) monocytes. CD11c(hi) DC ablation resulted in the accumulation of IL-17(+)CD4(+) Th17 cells in the CNS, thereby leading to lower ratio of Tregs to Th17 cells. This result was corroborated by the higher expression levels of IL-17 and RORγT in CD4(+) T cells from the brains of CD11c(hi) DC-ablated mice. In addition, CD11c(hi) DC-ablated mice showed higher frequency and total number of inflammatory CD11b(+)Ly-6C(hi) monocytes, whereas CD11b(+)Ly-6C(lo) monocytes were detected with lower frequency and total number in CD11c(hi) DC-ablated mice. Furthermore, CD11c(hi) DC ablation altered the phenotype and function of CD11b(+)Ly-6C(lo) monocytes, resulting in lower levels of activation marker and anti-inflammatory cytokine (IL-10 and TGF-β) expression. Collectively, these results indicate that CD11c(hi) DC ablation caused an imbalance in CD4(+) Th17/Treg cells and CD11b(+)Ly-6C(hi)/Ly-6C(lo) monocytes in the lymphoid tissue and CNS during JE progression. This imbalanced orchestration of pro- and anti-inflammatory leukocytes following CD11c(hi) DC ablation may contribute to the exacerbation of JE.",2017 Jun 20,"['Choi, Jin Young', 'Kim, Jin Hyoung', 'Patil, Ajit Mahadev', 'Kim, Seong Bum', 'Uyangaa, Erdenebelig', 'Hossain, Ferdaus Mohd Altaf', 'Eo, Seong Kug']",Immune Netw,,,True
3c6601ba74b263d57b6b7fc0fbb7868d6ad2b107,PMC,Fibrinous pericarditis secondary to bacterial infection in a cat,http://dx.doi.org/10.1292/jvms.17-0051,PMC5487798,28484098,CC BY-NC-ND,"A three-year-old spayed domestic short-haired cat presented for evaluation of weight loss, cardiomegaly and pleural effusion. Echocardiographic examination demonstrated a thickened pericardium with mild pericardial effusion and a large volume of pleural effusion characterized by exudate. Although the cat was treated with antibiotics, the clinical symptoms did not improve. The cat developed dyspnea and died on day 7. Necropsy revealed a large amount of modified transudates ascites, pleural effusion and markedly dilated pericardium. Histopathological examination revealed severe exudation of fibrin and granulation tissue in a thick layer of the epicardium. The cat was diagnosed with fibrinous pericarditis secondary to bacterial infection.",2017 Jun 5,"['TAGAWA, Michihito', 'KURASHIMA, Chihiro', 'SHIMBO, Genya', 'OMURA, Hiroshi', 'KOYAMA, Kenji', 'HORIUCHI, Noriyuki', 'KOBAYASHI, Yoshiyasu', 'KAWAMOTO, Keiko', 'MIYAHARA, Kazuro']",J Vet Med Sci,,,True
9a8ffb71928a37a550e689f36fa3196493e036fe,PMC,HIV virions sense plasma membrane heterogeneity for cell entry,http://dx.doi.org/10.1126/sciadv.1700338,PMC5489272,28782011,CC BY-NC,"It has been proposed that cholesterol in host cell membranes plays a pivotal role for cell entry of HIV. However, it remains largely unknown why virions prefer cholesterol-rich heterogeneous membranes to uniformly fluid membranes for membrane fusion. Using giant plasma membrane vesicles containing cholesterol-rich ordered and cholesterol-poor fluid lipid domains, we demonstrate that the HIV receptor CD4 is substantially sequestered into ordered domains, whereas the co-receptor CCR5 localizes preferentially at ordered/disordered domain boundaries. We also show that HIV does not fuse from within ordered regions of the plasma membrane but rather at their boundaries. Ordered/disordered lipid domain coexistence is not required for HIV attachment but is a prerequisite for successful fusion. We propose that HIV virions sense and exploit membrane discontinuities to gain entry into cells. This study provides surprising answers to the long-standing question about the roles of cholesterol and ordered lipid domains in cell entry of HIV and perhaps other enveloped viruses.",2017 Jun 28,"['Yang, Sung-Tae', 'Kreutzberger, Alex J. B.', 'Kiessling, Volker', 'Ganser-Pornillos, Barbie K.', 'White, Judith M.', 'Tamm, Lukas K.']",Sci Adv,,,True
37f81abd2b26c35cab5401f0041f5af64f6184de,PMC,HIV virions sense plasma membrane heterogeneity for cell entry,http://dx.doi.org/10.1126/sciadv.1700338,PMC5489272,28782011,CC BY-NC,"It has been proposed that cholesterol in host cell membranes plays a pivotal role for cell entry of HIV. However, it remains largely unknown why virions prefer cholesterol-rich heterogeneous membranes to uniformly fluid membranes for membrane fusion. Using giant plasma membrane vesicles containing cholesterol-rich ordered and cholesterol-poor fluid lipid domains, we demonstrate that the HIV receptor CD4 is substantially sequestered into ordered domains, whereas the co-receptor CCR5 localizes preferentially at ordered/disordered domain boundaries. We also show that HIV does not fuse from within ordered regions of the plasma membrane but rather at their boundaries. Ordered/disordered lipid domain coexistence is not required for HIV attachment but is a prerequisite for successful fusion. We propose that HIV virions sense and exploit membrane discontinuities to gain entry into cells. This study provides surprising answers to the long-standing question about the roles of cholesterol and ordered lipid domains in cell entry of HIV and perhaps other enveloped viruses.",2017 Jun 28,"['Yang, Sung-Tae', 'Kreutzberger, Alex J. B.', 'Kiessling, Volker', 'Ganser-Pornillos, Barbie K.', 'White, Judith M.', 'Tamm, Lukas K.']",Sci Adv,,,False
7818d1ffe60f6ea1d6b44e73402132ce41453ab2,PMC,Sequence analysis of the spike gene of Porcine epidemic diarrhea virus isolated from South China during 2011–2015,http://dx.doi.org/10.4142/jvs.2017.18.2.237,PMC5489471,27515262,CC BY-NC,"The spike gene of porcine epidemic diarrhea virus (PEDV) was sequenced from 55 South China field strains isolated from pigs with symptoms of diarrhea. The sequences were compared within the set of field strains as well as with reference strains available in GenBank. Within the 55 South China PEDV field strains, the deduced amino acid sequence identities ranged from 93.8% to 99.9 % and ranged from 90.7% to 99.5% when compared with the foreign reference strains in GenBank. Our phylogenetic analysis showed that 10 of the 55 South China PEDV strains belonged to G1b and 45 belonged to G2b.",2017 Jun 22,"['Zhao, Xiaoya', 'Li, Zhili', 'Zeng, Xiduo', 'Zhang, Guanqun', 'Niu, Jianqiang', 'Sun, Baoli', 'Ma, Jingyun']",J Vet Sci,,,True
a3cf3a5dc7b63848aef753bf664fc8c7815de577,PMC,Middle East respiratory syndrome clinical practice guideline for hemodialysis facilities,http://dx.doi.org/10.23876/j.krcp.2017.36.2.111,PMC5491158,28680819,CC BY-NC,"The Korean Society of Nephrology participated in the task force team consisting of government authorities and civilian experts to prevent and control the spread of Middle East respiratory syndrome (MERS) in 2015. The Korean Society of Nephrology MERS Task Force Team took an immediate action and drafted ‘the clinical recommendation for hemodialysis facilities’ to follow when the first and the only confirmed case was reported in the hemodialysis unit. Owing to the dedicated support from medical doctors, dialysis nurses, and related medical companies, we could prevent further transmission of MERS infection successfully in hemodialysis units. This special report describes the experience of infection control during MERS outbreak in 2015 and summarizes the contents of ‘the clinical practice guideline for hemodialysis facilities dealing with MERS patients’ built upon our previous experience.",2017 Jun 30,"['Park, Hayne Cho', 'Lee, Young-Ki', 'Lee, Sang-Ho', 'Yoo, Kyung Don', 'Jeon, Hee Jung', 'Ryu, Dong-Ryeol', 'Kim, Seong Nam', 'Sohn, Seung Hwan', 'Chun, Rho Won', 'Choi, Kyu Bok', None]",Kidney Res Clin Pract,,,True
d8b4fdc1562a67f7207de2d81e6ac4c854190579,PMC,Middle East respiratory syndrome clinical practice guideline for hemodialysis facilities,http://dx.doi.org/10.23876/j.krcp.2017.36.2.111,PMC5491158,28680819,CC BY-NC,"The Korean Society of Nephrology participated in the task force team consisting of government authorities and civilian experts to prevent and control the spread of Middle East respiratory syndrome (MERS) in 2015. The Korean Society of Nephrology MERS Task Force Team took an immediate action and drafted ‘the clinical recommendation for hemodialysis facilities’ to follow when the first and the only confirmed case was reported in the hemodialysis unit. Owing to the dedicated support from medical doctors, dialysis nurses, and related medical companies, we could prevent further transmission of MERS infection successfully in hemodialysis units. This special report describes the experience of infection control during MERS outbreak in 2015 and summarizes the contents of ‘the clinical practice guideline for hemodialysis facilities dealing with MERS patients’ built upon our previous experience.",2017 Jun 30,"['Park, Hayne Cho', 'Lee, Young-Ki', 'Lee, Sang-Ho', 'Yoo, Kyung Don', 'Jeon, Hee Jung', 'Ryu, Dong-Ryeol', 'Kim, Seong Nam', 'Sohn, Seung Hwan', 'Chun, Rho Won', 'Choi, Kyu Bok', None]",Kidney Res Clin Pract,,,False
c3a6451d69ba69ded9a9e9683d2668237482399f,PMC,Th17 profile in COPD exacerbations,http://dx.doi.org/10.2147/COPD.S136592,PMC5491572,28694696,CC BY-NC,"COPD is characterized by an ongoing inflammatory process of the airways that leads to obstruction or limitation of airflow. It is mainly associated with exposure to cigarette smoke. In addition, it is considered, at present, a serious public health problem, ranking fourth in mortality worldwide. Many cells participate in the pathophysiology of COPD, the most important are neutrophils, macrophages and CD4+ and CD8+ T cells. Neutrophil migration to the inflammation area could be mediated largely by cytokines related to CD4+ Th17 lymphocytes, because it has been shown that IL-17A, IL-17F and IL-22 act as inducers for CXCL8, CXCL1, CXCL5, G-CSF, and GM-CSF secretion by epithelial cells of the airways. The aims of these molecules are differentiation, proliferation and recruitment of neutrophils. Furthermore, it is believed that CD4+ lymphocytes Th17 may be involved in protection against pathogens for which Th1 and Th2 are not prepared to fight. In COPD exacerbations, there is an increased cellularity in the lung region and respiratory tract. Therefore, the increase in the number of neutrophils and macrophages in the airways and the increase in proinflammatory cytokines are directly related to the severity of exacerbations and that is the importance of the functions of Th17 profile in this entity.",2017 Jun 22,"['Ponce-Gallegos, Marco Antonio', 'Ramírez-Venegas, Alejandra', 'Falfán-Valencia, Ramcés']",Int J Chron Obstruct Pulmon Dis,,,True
528411eebd9d3c1b16ab5ec425724551e7837c5d,PMC,Hydrocortisone therapy in a cat with vasopressor‐refractory septic shock and suspected critical illness‐related corticosteroid insufficiency,http://dx.doi.org/10.1002/ccr3.1018,PMC5494402,28680609,CC BY-NC-ND,"A 27‐month‐old female cat was presented with septic peritonitis secondary to a ruptured pyometra and subsequent pyothorax. Vasopressor‐refractory septic shock led to a suspicion of critical illness‐related corticosteroid insufficiency, successfully treated with intravenous hydrocortisone. Previous megestrol acetate administration may have played a role in the development of adrenocortical dysfunction.",2017 May 31,"['Pisano, Simone R. R.', 'Howard, Judith', 'Posthaus, Horst', 'Kovacevic, Alan', 'Yozova, Ivayla D.']",Clin Case Rep,,,True
c7f8f1365c454c71574aaaf83fa3d6bdd92e992b,PMC,Pulmonary manifestation of Plasmodium falciparum malaria: Case reports and review of the literature,http://dx.doi.org/10.1016/j.rmcr.2017.06.014,PMC5496505,28702342,CC BY-NC-ND,"Pulmonary complications, including acute respiratory distress syndrome (ARDS), are well described in P. falciparum (PF) and to a lesser extent in other malaria species. In non-endemic areas, malaria diagnosis may be overlooked; if a thorough travel history is not obtained on all patients with acute febrile illness. Three patients with malaria associated respiratory distress were admitted to our intensive care unit. The diagnosis was delayed; however, all patients received artesunate and intensive therapy with a satisfactory outcome. One patient presented with respiratory disease while the others developed ARDS during or following appropriate therapy. Similarly, level of parasitemia was variable ranging from undetectable to over 5%. Variability in timing and severity of illness is exciting and gives emphasis to the different pathological processes contemplated in this complication.",2017 Jun 30,"['Elzein, Fatehi', 'Mohammed, Nazik', 'Ali, Najoud', 'Bahloul, Abdelkarim', 'Albadani, Abeer', 'Alsherbeeni, Nisreen']",Respir Med Case Rep,,,False
533f8d39de2e16fb92614d2441621e8fddd85bbe,PMC,"Proenkephalin, Neutrophil Gelatinase-Associated Lipocalin, and Estimated Glomerular Filtration Rates in Patients With Sepsis",http://dx.doi.org/10.3343/alm.2017.37.5.388,PMC5500737,28643487,CC BY-NC,"BACKGROUND: Proenkephalin (PENK) has been suggested as a novel biomarker for kidney function. We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (eGFR) in septic patients. METHODS: A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis. PENK and NGAL concentrations were measured and GFR was estimated by using the isotope dilution mass spectrometry traceable-Modification of Diet in Renal Disease (MDRD) Study and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations: CKD-EPI(Cr), CDK-EPI(CysC), and CKD-EPI(Cr-CysC). The PENK, NGAL, and eGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes. RESULTS: The PENK, NGAL, and eGFR results were significantly associated with sepsis severity and differed significantly between patients with and without AKI only in the sepsis group (all P<0.05). PENK was superior to NGAL in predicting AKI (P=0.022) and renal replacement therapy (RRT) (P=0.0085). Regardless of the variable GFR category by the different eGFR equations, PENK showed constant and significant associations with all eGFR equations. Unlike NGAL, PENK was not influenced by inflammation and predicted the 30-day mortality. CONCLUSIONS: PENK is a highly sensitive and objective biomarker of AKI and RRT and is useful for prognosis prediction in septic patients. With its diagnostic robustness and predictive power for survival, PENK constitutes a promising biomarker in critical care settings including sepsis.",2017 Sep 20,"['Kim, Hanah', 'Hur, Mina', 'Lee, Seungho', 'Marino, Rossella', 'Magrini, Laura', 'Cardelli, Patrizia', 'Struck, Joachim', 'Bergmann, Andreas', 'Hartmann, Oliver', 'Di Somma, Salvatore', None]",Ann Lab Med,,,True
cfb3735e8a8570efe9bc510fb05fe73441b00314,PMC,Comparison of the Luminex xTAG Respiratory Viral Panel Fast v2 Assay With Anyplex II RV16 Detection Kit and AdvanSure RV Real-Time RT-PCR Assay for the Detection of Respiratory Viruses,http://dx.doi.org/10.3343/alm.2017.37.5.408,PMC5500739,28643489,CC BY-NC,"BACKGROUND: The accurate and rapid identification of the causative viruses is important for the timely diagnosis and management of respiratory infections. Multiplex molecular diagnostic techniques have been widely adopted to detect respiratory viruses. We compared the results of a newly upgraded, multiplex, molecular bead-based respiratory viral panel (RVP) assay with the results of Anyplex II RV16 detection kit and AdvanSure RV real-time RT-PCR assay. METHODS: We tested 254 respiratory specimens and cultured viral strains using the Luminex xTAG RVP Fast v2 assay (Luminex Molecular Diagnostics, Canada) and Anyplex II RV16 detection kit and compared the results. Specimens showing discordant results between the two assays were tested with a AdvanSure RV real-time RT-PCR assay. RESULTS: Of the 254 respiratory specimens, there was total agreement in the results between the xTAG RVP Fast v2 assay and the other real-time PCR assay in 94.1–100% of the specimens. The agreement levels were relatively low (94.1–97.6%) for specimens of adenovirus, coronavirus NL63, and parainfluenza type 3. In comparison to the other assay, the xTAG RVP Fast v2 assay detected a higher number of parainfluenza type 3 (4 cases) and metapneumovirus (9 cases). CONCLUSIONS: The xTAG RVP Fast v2 assay showed comparable capabilities compared with the other assays; it will be useful for identifying respiratory viral infections in patients with respiratory symptoms. Clinicians should be aware of the characteristics of the assays they use, since different assays show different detectability for each virus.",2017 Sep 20,"['Ko, Dae-Hyun', 'Kim, Hyun Soo', 'Hyun, Jungwon', 'Kim, Han-Sung', 'Kim, Jae-Seok', 'Park, Kyoung Un', 'Song, Wonkeun']",Ann Lab Med,,,True
91bfca3d386f93c5b083464adb93c8d36f773fb0,PMC,Recurrent rhinovirus infections in a child with inherited MDA5 deficiency,http://dx.doi.org/10.1084/jem.20161759,PMC5502429,28606988,CC BY-NC-SA,"MDA5 is a cytosolic sensor of double-stranded RNA (ds)RNA including viral byproducts and intermediates. We studied a child with life-threatening, recurrent respiratory tract infections, caused by viruses including human rhinovirus (HRV), influenza virus, and respiratory syncytial virus (RSV). We identified in her a homozygous missense mutation in IFIH1 that encodes MDA5. Mutant MDA5 was expressed but did not recognize the synthetic MDA5 agonist/(ds)RNA mimic polyinosinic-polycytidylic acid. When overexpressed, mutant MDA5 failed to drive luciferase activity from the IFNB1 promoter or promoters containing ISRE or NF-κB sequence motifs. In respiratory epithelial cells or fibroblasts, wild-type but not knockdown of MDA5 restricted HRV infection while increasing IFN-stimulated gene expression and IFN-β/λ. However, wild-type MDA5 did not restrict influenza virus or RSV replication. Moreover, nasal epithelial cells from the patient, or fibroblasts gene-edited to express mutant MDA5, showed increased replication of HRV but not influenza or RSV. Thus, human MDA5 deficiency is a novel inborn error of innate and/or intrinsic immunity that causes impaired (ds)RNA sensing, reduced IFN induction, and susceptibility to the common cold virus.",2017 Jul 3,"['Lamborn, Ian T.', 'Jing, Huie', 'Zhang, Yu', 'Drutman, Scott B.', 'Abbott, Jordan K.', 'Munir, Shirin', 'Bade, Sangeeta', 'Murdock, Heardley M.', 'Santos, Celia P.', 'Brock, Linda G.', 'Masutani, Evan', 'Fordjour, Emmanuel Y.', 'McElwee, Joshua J.', 'Hughes, Jason D.', 'Nichols, Dave P.', 'Belkadi, Aziz', 'Oler, Andrew J.', 'Happel, Corinne S.', 'Matthews, Helen F.', 'Abel, Laurent', 'Collins, Peter L.', 'Subbarao, Kanta', 'Gelfand, Erwin W.', 'Ciancanelli, Michael J.', 'Casanova, Jean-Laurent', 'Su, Helen C.']",J Exp Med,,,True
dca39851b72d6aa2d8e9e4ab0d79b3f01dd88ba5,PMC,Recurrent rhinovirus infections in a child with inherited MDA5 deficiency,http://dx.doi.org/10.1084/jem.20161759,PMC5502429,28606988,CC BY-NC-SA,"MDA5 is a cytosolic sensor of double-stranded RNA (ds)RNA including viral byproducts and intermediates. We studied a child with life-threatening, recurrent respiratory tract infections, caused by viruses including human rhinovirus (HRV), influenza virus, and respiratory syncytial virus (RSV). We identified in her a homozygous missense mutation in IFIH1 that encodes MDA5. Mutant MDA5 was expressed but did not recognize the synthetic MDA5 agonist/(ds)RNA mimic polyinosinic-polycytidylic acid. When overexpressed, mutant MDA5 failed to drive luciferase activity from the IFNB1 promoter or promoters containing ISRE or NF-κB sequence motifs. In respiratory epithelial cells or fibroblasts, wild-type but not knockdown of MDA5 restricted HRV infection while increasing IFN-stimulated gene expression and IFN-β/λ. However, wild-type MDA5 did not restrict influenza virus or RSV replication. Moreover, nasal epithelial cells from the patient, or fibroblasts gene-edited to express mutant MDA5, showed increased replication of HRV but not influenza or RSV. Thus, human MDA5 deficiency is a novel inborn error of innate and/or intrinsic immunity that causes impaired (ds)RNA sensing, reduced IFN induction, and susceptibility to the common cold virus.",2017 Jul 3,"['Lamborn, Ian T.', 'Jing, Huie', 'Zhang, Yu', 'Drutman, Scott B.', 'Abbott, Jordan K.', 'Munir, Shirin', 'Bade, Sangeeta', 'Murdock, Heardley M.', 'Santos, Celia P.', 'Brock, Linda G.', 'Masutani, Evan', 'Fordjour, Emmanuel Y.', 'McElwee, Joshua J.', 'Hughes, Jason D.', 'Nichols, Dave P.', 'Belkadi, Aziz', 'Oler, Andrew J.', 'Happel, Corinne S.', 'Matthews, Helen F.', 'Abel, Laurent', 'Collins, Peter L.', 'Subbarao, Kanta', 'Gelfand, Erwin W.', 'Ciancanelli, Michael J.', 'Casanova, Jean-Laurent', 'Su, Helen C.']",J Exp Med,,,False
dedfabd7d2b04bcc8274b1f49667c821281d3c63,PMC,Heat shock protein 90β in the Vero cell membrane binds Japanese encephalitis virus,http://dx.doi.org/10.3892/ijmm.2017.3041,PMC5505021,28656253,CC BY-NC-ND,"The pathogenesis of Japanese encephalitis virus (JEV) is complex and unclearly defined, and in particular, the effects of the JEV receptor (JEVR) on diverse susceptible cells are elusive. In contrast to previous studies investigating JEVR in rodent or mosquito cells, in this study, we used primate Vero cells instead. We noted that few novel proteins co-immunoprecipitated with JEV, and discovered that one of these was heat shock protein 90β (HSP90β), which was probed by mass spectrometry with the highest score of 60.3 after questing the monkey and human protein databases. The specific HSP90β-JEV binding was confirmed by western blot analysis under non-reducing conditions, and this was significantly inhibited by an anti-human HSP90β monoclonal antibody in a dose-dependent manner, as shown by immunofluorescence assay and flow cytometry. In addition, the results of confocal laser scanning microscopic examination demonstrated that the HSP90β-JEV binding occurred on the Vero cell surface. Finally, JEV progeny yields determined by plaque assay were also markedly decreased in siRNA-treated Vero cells, particularly at 24 and 36 h post-infection. Thus, our data indicate that HSP90β is a binding receptor for JEV in Vero cells.",2017 Aug 26,"['Wang, Yuan', 'Li, Yan', 'Ding, Tianbing']",Int J Mol Med,,,True
85e8b1143c1869125270527aa26d4e48ad63fb5b,PMC,Travellers and influenza: risks and prevention,http://dx.doi.org/10.1093/jtm/taw078,PMC5505480,28077609,CC BY-NC,"Background: Influenza viruses are among the major causes of serious human respiratory tract infection worldwide. In line with the high disease burden attributable to influenza, these viruses play an important, but often neglected, role in travel medicine. Guidelines and recommendations regarding prevention and management of influenza in travellers are scarce. Of special interest for travel medicine are risk populations and also circumstances that facilitate influenza virus transmission and spread, like travel by airplane or cruise ship and mass gatherings. Methods: We conducted a PUBMED/MEDLINE search for a combination of the MeSH terms Influenza virus, travel, mass gathering, large scale events and cruise ship. In addition we gathered guidelines and recommendations from selected countries and regarding influenza prevention and management in travellers. By reviewing these search results in the light of published knowledge in the fields of influenza prevention and management, we present best practice advice for the prevention and management of influenza in travel medicine. Results: Seasonal influenza is among the most prevalent infectious diseases in travellers. Known host-associated risk factors include extremes of age and being immune-compromised, while the most relevant environmental factors are associated with holiday cruises and mass gatherings. Conclusions: Pre-travel advice should address influenza and its prevention for travellers, whenever appropriate on the basis of the epidemiological situation concerned. Preventative measures should be strongly recommended for travellers at high-risk for developing complications. In addition, seasonal influenza vaccination should be considered for any traveller wishing to reduce the risk of incapacitation, particularly cruise ship crew and passengers, as well as those participating in mass gatherings. Besides advice concerning preventive measures and vaccination, advice on the use of antivirals may be considered for some travellers.",2016 Dec 24,"['Goeijenbier, M.', 'van Genderen, P.', 'Ward, B. J.', 'Wilder-Smith, A.', 'Steffen, R.', 'Osterhaus, A. D. M. E.']",J Travel Med,,,True
a02f53bba04cb55cd70c09e2299f3ab1556943fb,PMC,2017 ACVIM Forum Research Abstract Program,http://dx.doi.org/10.1111/jvim.14778,PMC5508335,,CC BY-NC,,2017 Jun 15 Jul-Aug,,J Vet Intern Med,,,True
a6ea21d8e8f97c41b9f69ee6c5d82f5c1a11107b,PMC,Hepatitis E Virus–Associated Meningoencephalitis in a Lung Transplant Recipient Diagnosed by Clinical Metagenomic Sequencing,http://dx.doi.org/10.1093/ofid/ofx121,PMC5508774,28721353,CC BY-NC-ND,"Hepatitis E virus (HEV) infection uncommonly causes chronic hepatitis and neurologic disease. We describe a case of genotype 3a HEV meningoencephalitis diagnosed by metagenomic next-generation sequencing, illustrating the power of an unbiased molecular approach to microbial testing and the first reported case of HEV infection presumably acquired through lung transplantation.",2017 Jun 13,"['Murkey, Jamie A.', 'Chew, Kara W.', 'Carlson, Margrit', 'Shannon, Chelsea L.', 'Sirohi, Deepika', 'Sample, Hannah A.', 'Wilson, Michael R.', 'Vespa, Paul', 'Humphries, Romney M.', 'Miller, Steve', 'Klausner, Jeffrey D.', 'Chiu, Charles Y.']",Open Forum Infect Dis,,,True
dd0c5937b6cb58757f80bbc4ffb461e3c606df3a,PMC,Hepatitis E Virus–Associated Meningoencephalitis in a Lung Transplant Recipient Diagnosed by Clinical Metagenomic Sequencing,http://dx.doi.org/10.1093/ofid/ofx121,PMC5508774,28721353,CC BY-NC-ND,"Hepatitis E virus (HEV) infection uncommonly causes chronic hepatitis and neurologic disease. We describe a case of genotype 3a HEV meningoencephalitis diagnosed by metagenomic next-generation sequencing, illustrating the power of an unbiased molecular approach to microbial testing and the first reported case of HEV infection presumably acquired through lung transplantation.",2017 Jun 13,"['Murkey, Jamie A.', 'Chew, Kara W.', 'Carlson, Margrit', 'Shannon, Chelsea L.', 'Sirohi, Deepika', 'Sample, Hannah A.', 'Wilson, Michael R.', 'Vespa, Paul', 'Humphries, Romney M.', 'Miller, Steve', 'Klausner, Jeffrey D.', 'Chiu, Charles Y.']",Open Forum Infect Dis,,,False
73e7afead191100d40815046ec54385155e9921f,PMC,Hepatitis E Virus–Associated Meningoencephalitis in a Lung Transplant Recipient Diagnosed by Clinical Metagenomic Sequencing,http://dx.doi.org/10.1093/ofid/ofx121,PMC5508774,28721353,CC BY-NC-ND,"Hepatitis E virus (HEV) infection uncommonly causes chronic hepatitis and neurologic disease. We describe a case of genotype 3a HEV meningoencephalitis diagnosed by metagenomic next-generation sequencing, illustrating the power of an unbiased molecular approach to microbial testing and the first reported case of HEV infection presumably acquired through lung transplantation.",2017 Jun 13,"['Murkey, Jamie A.', 'Chew, Kara W.', 'Carlson, Margrit', 'Shannon, Chelsea L.', 'Sirohi, Deepika', 'Sample, Hannah A.', 'Wilson, Michael R.', 'Vespa, Paul', 'Humphries, Romney M.', 'Miller, Steve', 'Klausner, Jeffrey D.', 'Chiu, Charles Y.']",Open Forum Infect Dis,,,False
707804d48dc9d8ebd7016536cf785c6c0be25bf8,PMC,How HIV patients construct liveable identities in a shame based culture: the case of Singapore,http://dx.doi.org/10.1080/17482631.2017.1333899,PMC5510245,28641480,CC BY-NC,"This article interrogates the mainstream healthcare narrative that frames human immunodeficiency virus (HIV) as a chronic disease, and triangulates it with the lived experiences of people with HIV in Singapore. It also examines how HIV patients reconstruct their identities after the diagnosis of HIV. Four HIV patients (two males and two females) were interviewed in depth by an experienced medical social worker. Findings revealed that even as the illness trajectory of HIV has shifted from a terminal condition to a chronic one, living with HIV continues to be fraught with difficulty as society, especially in the Asian context, perceives HIV with much fear and disapproval. The participants had an overwhelming sense of shame when they were initially diagnosed with HIV and they had to reconstruct a liveable identity by containing the shroud of shame, reinforcing their normative identities and constructing new ones. These strategies help them to keep their shame at bay. This paper also unpacks nuanced insights of shame experienced by Chinese HIV patients in an Asian city dominated by Confucian values.",2017 Jun 22,"['Ho, Lai Peng', 'Goh, Esther C. L.']",Int J Qual Stud Health Well-being,,,True
786282089d03a2eaed7139f503755faa30dd741f,PMC,Impact of Middle East respiratory syndrome outbreak on the use of emergency medical resources in febrile patients,http://dx.doi.org/10.15441/ceem.16.166,PMC5511955,28717779,CC BY-NC,"OBJECTIVE: Outbreaks of transmissible respiratory infection are suspected to have significant effects on the health of pediatric and geriatric patients. The objective was to assess the impact of the Middle East respiratory syndrome (MERS) outbreak on the use of emergency resources. METHODS: An ecologic analysis of emergency department (ED) records between September and December 2015, was performed. Data was obtained from the National Emergency Department Information System database for Korea. All demographic and diagnostic data from patients presenting with febrile symptoms as a main complaint were collected. The data were compared to the equivalent period in the three years preceding the MERS outbreak in Korea. RESULTS: Following the MERS outbreak, there was an increase in overall ED visits by febrile patients and the proportion of visits by febrile patients, relative to total ED attendances. This effect was more prominent in the children under five years. The duration of the chief complaint before ED arrival and the length of ED stay were significantly increased among younger pediatric patients. Decreased body temperature on arrival was observed in younger pediatric patients. CONCLUSION: MERS outbreak appears to have had a significant effects on ED use by febrile patients. The use of emergency care services by pediatric patients makes them more vulnerable to an outbreak of a transmissable disease. An effective strategy to control emergency center visits by non-urgent febrile patients and provide proper medical services is urgently needed.",2017 Jun 30,"['Jeong, Hyunho', 'Jeong, Sikyoung', 'Oh, Juseok', 'Woo, Seon Hee', 'So, Byung Hak', 'Wee, Jeong Hee', 'Kim, Ji Hoon', 'Im, Ji Yong', 'Choi, Seung Pill', 'Park, Kyoungnam', 'Cho, Byul Nim Hee', 'Hong, Sungyoup']",Clin Exp Emerg Med,,,True
f37e28d5d912f4361695c361f5400b0045b88005,PMC,Persistence in Temporary Lung Niches: A Survival Strategy of Lung-Resident Memory CD8(+) T Cells,http://dx.doi.org/10.1089/vim.2017.0016,PMC5512299,28418771,CC BY-NC,"Respiratory virus infections, such as those mediated by influenza virus, parainfluenza virus, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus (SARS-CoV), rhinovirus, and adenovirus, are responsible for substantial morbidity and mortality, especially in children and older adults. Furthermore, the potential emergence of highly pathogenic strains of influenza virus poses a significant public health threat. Thus, the development of vaccines capable of eliciting long-lasting protective immunity to those pathogens is a major public health priority. CD8(+) Tissue-resident memory T (T(RM)) cells are a newly defined population that resides permanently in the nonlymphoid tissues including the lung. These cells are capable of providing local protection immediately after infection, thereby promoting rapid host recovery. Recent studies have offered new insights into the anatomical niches that harbor lung CD8(+) T(RM) cells, and also identified the requirement and limitations of T(RM) maintenance. However, it remains controversial whether lung CD8(+) T(RM) cells are continuously replenished by new cells from the circulation or permanently lodged in this site. A better understanding of how lung CD8(+) T(RM) cells are generated and maintained and the tissue-specific factors that drive local T(RM) formation is required for optimal vaccine development. This review focuses on recent advance in our understanding of CD8(+) T(RM) cell establishment and maintenance in the lung, and describes how those processes are uniquely regulated in this tissue.",2017 Jul 1,"Takamura, Shiki",Viral Immunol,,,True
643f2dd329f342e9e85753ab315722bc1120d0ef,PMC,Pediatric Mycoplasma pneumoniae Infection Presenting with Acute Cholestatic Hepatitis and Other Extrapulmonary Manifestations in the Absence of Pneumonia,http://dx.doi.org/10.5223/pghn.2017.20.2.124,PMC5517379,28730137,CC BY-NC,"Mycoplasma pneumoniae infections mainly involve respiratory tract; however, also can manifestate other symptoms by site involved. Extrapulmonary manifestations of M. pneumoniae infection are rarely known to occur without pneumonia. Herein we report a case of a 9-year-old boy who presented with acute cholestatic hepatitis in the absence of pneumonia. Rhabdomyolysis, skin rash, and initial laboratory results suspicious of disseminated intravascular coagulopathy were also observed in this patient. M. pneumoniae infection was identified by a 4-fold increase in immunoglobulin G antibodies to M. pneumoniae between acute and convalescent sera by enzyme-linked immunosorbent assay. This is the first pediatric case in Korea of M. pneumoniae infection presenting with acute cholestatic hepatitis in the absence of pneumonia.",2017 Jun 28,"['Song, Won Jae', 'Kang, Ben', 'Lee, Hwa Pyung', 'Cho, Joongbum', 'Lee, Hae Jeong', 'Choe, Yon Ho']",Pediatr Gastroenterol Hepatol Nutr,,,True
af0768141c00f1317b4fb9c74080d1510de93f32,PMC,Developing Interactive Antimicrobial Stewardship and Infection Prevention Curricula for Diverse Learners: A Tailored Approach,http://dx.doi.org/10.1093/ofid/ofx117,PMC5522578,28748196,CC BY-NC-ND,"BACKGROUND. To impart principles of antimicrobial stewardship (AS) and infection prevention and control (IPC), we developed a curriculum tailored to the diverse aptitudes of learners at our medical center. METHODS. We integrated case-based modules, group learning activities, smartphone applications (apps), decision support tools, and prescription audit and feedback into curricula of the medical school, medicine residency program, infectious diseases (ID) fellowship program, and hospital medicine program operations. Interventions were implemented in 2012–2016 using a quasi-experimental before-and-after study design, and this was assessed using pre- and postintervention surveys or audit of antibiotic prescriptions. RESULTS. Over 180 medical students participated in the AS and IPC seminars. After smartphone app introduction, 69% reported using the app as their preferred source of antibiotic information. Approximately 70% of students felt comfortable prescribing antibiotics for a known infection compared with 40% at baseline (P = .02), and approximately 83% were able to identify the appropriate personal protective equipment for specific scenarios. Approximately 99% agreed that they have a role in promoting patient safety and preventing healthcare-associated infections as medical students. At 20 months, appropriateness of trainee antibiotic prescriptions increased by 20% (P < .01). Almost all ID fellows indicated that the AS and IPC seminar was a vital training supplement. Uptake of internist antibiotic recommendations using AS decision support tools was approximately 70%. CONCLUSIONS. All 5 interventions addressed learning objectives and knowledge gaps and are applicable across a range of environments. Evaluating long-term impact of our curriculum is the focus of future study.",2017 Jul 20,"['Nori, Priya', 'Madaline, Theresa', 'Munjal, Iona', 'Bhar, Shubha', 'Guo, Yi', 'Seo, Susan K.', 'Porrovecchio, Andrea', 'Gancher, Elizabeth', 'Nosanchuk, Joshua', 'Pirofski, Liise-anne', 'Ostrowsky, Belinda']",Open Forum Infect Dis,,,True
b8f3e1eae904d969c78f5fcd89e203d858fce89d,PMC,Repurposed Therapeutic Agents Targeting the Ebola Virus: A Systematic Review,http://dx.doi.org/10.1016/j.curtheres.2017.01.007,PMC5522984,28761574,CC BY-NC-ND,"BACKGROUND: The Ebola virus has been responsible for numerous outbreaks since the 1970s, with the most recent outbreak taking place between 2014 and 2016 and causing an international public health emergency. Ebola virus disease (EVD) has a high mortality rate and no approved targeted treatment exists to date. A number of established drugs are being considered as potential therapeutic agents for the treatment of EVD. OBJECTIVE: We aimed to identify potential drug repositioning candidates and to assess the scientific evidence available on their efficacy. METHODS: We conducted a systematic literature search in MEDLINE, Embase, and other relevant trial registry platforms for studies published between January 1976 and January 2017. We included drug screening, preclinical studies, and clinical studies on repurposed drugs for the treatment of EVD. The risk of bias for animal studies and nonrandomized clinical studies was assessed. The quality of reporting for case series and case reports was evaluated. Finally, we selected drugs approved by established regulatory authorities, which have positive in vitro study outcomes and at least one additional animal or clinical trial. RESULTS: We identified 3301 publications, of which 37 studies fulfilled our inclusion criteria. Studies were highly heterogeneous in terms of study type, methodology, and intervention. The risk of bias was high for 13 out of 14 animal studies. We selected 11 drugs with potential anti-EVD therapeutic effects and summarized their evidence. CONCLUSIONS: Several established drugs may have therapeutic effects on EVD, but the quality and quantity of current scientific evidence is lacking. This review highlights the need for well-designed and conducted preclinical and clinical research to establish the efficacy of potential repurposed drugs against EVD.",2017 Feb 2,"['Sweiti, Hussein', 'Ekwunife, Obinna', 'Jaschinski, Thomas', 'Lhachimi, Stefan K.']",Curr Ther Res Clin Exp,,,False
89cc80396595df1ebb851e602666945754ab0257,PMC,Concomitant multiple myeloma and probable phaeochromocytoma in a cat,http://dx.doi.org/10.1177/2055116917719209,PMC5524243,28839945,CC BY-NC,"CASE SUMMARY: Herein a drug-resistant IgG-lambda-type multiple myeloma associated with probable phaeochromocytoma in a cat is described. A 12-year-old cat presented with weakness, weight loss, progressive blindness and open-mouth breathing, in addition to polyuria and polydipsia of 2 months’ duration. Abdominal ultrasonography revealed a left adrenal mass. Phaeochromocytoma was suspected on the basis of cytology and was associated with systemic hypertension. Biochemistry showed hyperproteinaemia. Serum protein electrophoresis revealed a narrow spike in the gamma region, identified as IgG lambda type at immunoelectrophoresis. Bone marrow cytology revealed an infiltrate with numerous mature plasma cells. The cat was resistant to two different drugs for multiple myeloma and was euthanased 6 months later because of anorexia and persistent poor general condition. RELEVANCE AND NOVEL INFORMATION: This is the first clinical description of multiple myeloma associated with a suspected phaeochromocytoma in a cat.",2017 Jul 21,"Cervone, Mario",JFMS Open Rep,,,True
bca792def155d06e618f4fe78f6f4178ed5e1b69,PMC,Novel characteristics identified in two cases of feline cowpox virus infection,http://dx.doi.org/10.1177/2055116917717191,PMC5528940,28839944,CC BY-NC,"CASE SERIES SUMMARY: This case series discusses novel characteristics identified in two cases of cowpox. One presented with upper airway signs, and was identified to have a focal laryngeal lesion. The other had central neurological signs at the terminal stages, with intracytoplasmic inclusion bodies identified within the cerebral hemispheres on histopathology. RELEVANCE AND NOVEL INFORMATION: Currently, cowpox would be an unlikely consideration in patients with neurological signs or upper respiratory noise. These cases both document novel presentations of cowpox infection, which clinicians should be aware of and consider as differential diagnoses in patients with these atypical presentations.",2017 Jul 11,"['Breheny, Craig R', 'Fox, Victoria', 'Tamborini, Alice', 'O’Halloran, Conor', 'Robertson, Elise', 'Cazzini, Paola', 'Birn-Jeffery, Daniela', 'Henkin, Julia', 'Schwarz, Tobias', 'Scase, Tim', 'Powell, Roger', 'Gunn-Moore, Danièlle']",JFMS Open Rep,,,True
1f26b5e8291ea1ddc0a3131e8f93f7272093799e,PMC,The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care,http://dx.doi.org/10.1177/2374289517708309,PMC5528950,28815200,CC BY-NC,"An explosion of knowledge and technology is revolutionizing medicine and patient care. Novel testing must be brought to the clinic with safety and accuracy, but also in a timely and cost-effective manner, so that patients can benefit and laboratories can offer testing consistent with current guidelines. Under the oversight provided by the Clinical Laboratory Improvement Amendments, laboratories have been able to develop and optimize laboratory procedures for use in-house. Quality improvement programs, interlaboratory comparisons, and the ability of laboratories to adjust assays as needed to improve results, utilize new sample types, or incorporate new mutations, information, or technologies are positive aspects of Clinical Laboratory Improvement Amendments oversight of laboratory-developed procedures. Laboratories have a long history of successful service to patients operating under Clinical Laboratory Improvement Amendments. A series of detailed clinical examples illustrating the quality and positive impact of laboratory-developed procedures on patient care is provided. These examples also demonstrate how Clinical Laboratory Improvement Amendments oversight ensures accurate, reliable, and reproducible testing in clinical laboratories.",2017 Jul 16,"['Kaul, Karen L.', 'Sabatini, Linda M.', 'Tsongalis, Gregory J.', 'Caliendo, Angela M.', 'Olsen, Randall J.', 'Ashwood, Edward R.', 'Bale, Sherri', 'Benirschke, Robert', 'Carlow, Dean', 'Funke, Birgit H.', 'Grody, Wayne W.', 'Hayden, Randall T.', 'Hegde, Madhuri', 'Lyon, Elaine', 'Murata, Kazunori', 'Pessin, Melissa', 'Press, Richard D.', 'Thomson, Richard B.']",Acad Pathol,,,True
433c16daf21bb7f5f0d6379d67fe0917c2aa0281,PMC,Neurological Complications during Treatment of Middle East Respiratory Syndrome,http://dx.doi.org/10.3988/jcn.2017.13.3.227,PMC5532318,28748673,CC BY-NC,"BACKGROUND AND PURPOSE: Middle East respiratory syndrome (MERS) has a high mortality rate and pandemic potential. However, the neurological manifestations of MERS have rarely been reported since it first emerged in 2012. METHODS: We evaluated four patients with laboratory-confirmed MERS coronavirus (CoV) infections who showed neurological complications during MERS treatment. These 4 patients were from a cohort of 23 patients who were treated at a single designated hospital during the 2015 outbreak in the Republic of Korea. The clinical presentations, laboratory findings, and prognoses are described. RESULTS: Four of the 23 admitted MERS patients reported neurological symptoms during or after MERS-CoV treatment. The potential diagnoses in these four cases included Bickerstaff's encephalitis overlapping with Guillain-Barré syndrome, intensive-care-unit-acquired weakness, or other toxic or infectious neuropathies. Neurological complications did not appear concomitantly with respiratory symptoms, instead being delayed by 2–3 weeks. CONCLUSIONS: Neuromuscular complications are not rare during MERS treatment, and they may have previously been underdiagnosed. Understanding the neurological manifestations is important in an infectious disease such as MERS, because these symptoms are rarely evaluated thoroughly during treatment, and they may interfere with the prognosis or require treatment modification.",2017 Jul 30,"['Kim, Jee-Eun', 'Heo, Jae-Hyeok', 'Kim, Hye-ok', 'Song, Sook-hee', 'Park, Sang-Soon', 'Park, Tai-Hwan', 'Ahn, Jin-Young', 'Kim, Min-Ky', 'Choi, Jae-Phil']",J Clin Neurol,,,True
b7bf3bca72a759d1b1c4b003ce431ee58d0dbe27,PMC,Nanoparticle orientationally displayed antigen epitopes improve neutralizing antibody level in a model of porcine circovirus type 2,http://dx.doi.org/10.2147/IJN.S140789,PMC5533572,28769561,CC BY-NC,"Recent advancements in biotechnology have enabled the rapid identification and subsequent expression of pathogenic microbial major antigens that induce protective immune responses. However, subunit vaccines have not been successfully commercialized mainly due to the lack of sufficient levels of neutralizing antibodies (NAs). High levels of NA rely on the efficient recognition and cross-linking of multiple neutralizing epitopes with B-cell receptors (BCRs). Nanoparticles are able to display coupled antigenic arrays at high density and provide multiple binding molecular scenarios with BCRs. The high-resolution antigenic structure makes it possible to accurately display stable neutralizing epitopes. Therefore, the development of a nanovaccine that orientationally displays neutralizing epitopes is a feasible strategy. To address this hypothesis, the capsid (Cap) protein of porcine circovirus type 2 as model antigen was conjugated to gold nanoparticles (AuNPs) through direct reaction of the mercapto group of the unique cysteines with AuNPs, rendering Cap-AuNPs to have neutralizing epitopes on outer surface and an immunodominant epitope buried within the inner surface. In vitro studies showed that AuNPs promoted the phagocytosis of Cap protein and NA levels were significantly improved, meanwhile antibody levels against the immunodominant epitope was significantly reduced. In mouse studies, Cap-AuNP-immunized mice displayed a high production of interleukin (IL)-4, IL-10, and interferon-γ, suggesting that Cap-AuNPs can effectively activate CD4(+) and CD8(+) T cells and balance Th1 and Th2 cellular responses. This study presents a new vaccine design strategy based on antigen structure, where nanoparticles are coupled to antigens in well-ordered arrays and orientationally display neutralizing epitopes to enhance NA levels.",2017 Jul 24,"['Ding, Peiyang', 'Zhang, Teng', 'Li, Yafei', 'Teng, Man', 'Sun, Yaning', 'Liu, Xiao', 'Chai, Shujun', 'Zhou, Enmin', 'Jin, Qianyue', 'Zhang, Gaiping']",Int J Nanomedicine,,,True
34b3c509de48e972c90694eebad3ff0537f3d10b,PMC,Metagenomic Sequencing of an Echovirus 30 Genome From Cerebrospinal Fluid of a Patient With Aseptic Meningitis and Orchitis,http://dx.doi.org/10.1093/ofid/ofx138,PMC5534216,28761901,CC BY-NC-ND,"Enteroviruses cause a wide spectrum of clinical disease. In this study, we describe the case of a young man with orchitis and aseptic meningitis who was diagnosed with enterovirus infection. Using unbiased “metagenomic” massively parallel sequencing, we assembled a near-complete viral genome, the first use of this method for full-genome viral sequencing from cerebrospinal fluid. We found that the genome belonged to the subgroup echovirus 30, which is a common cause of aseptic meningitis but has not been previously reported to cause orchitis.",2017 Jul 28,"['Piantadosi, Anne', 'Mukerji, Shibani S', 'Chitneni, Pooja', 'Cho, Tracey A', 'Cosimi, Lisa A', 'Hung, Deborah T', 'Goldberg, Marcia B', 'Sabeti, Pardis C', 'Kuritzkes, Daniel R', 'Grad, Yonatan H']",Open Forum Infect Dis,,,True
f669a31865e1c7cb0c7cbb1f15e08889e15bc846,PMC,Metagenomic Sequencing of an Echovirus 30 Genome From Cerebrospinal Fluid of a Patient With Aseptic Meningitis and Orchitis,http://dx.doi.org/10.1093/ofid/ofx138,PMC5534216,28761901,CC BY-NC-ND,"Enteroviruses cause a wide spectrum of clinical disease. In this study, we describe the case of a young man with orchitis and aseptic meningitis who was diagnosed with enterovirus infection. Using unbiased “metagenomic” massively parallel sequencing, we assembled a near-complete viral genome, the first use of this method for full-genome viral sequencing from cerebrospinal fluid. We found that the genome belonged to the subgroup echovirus 30, which is a common cause of aseptic meningitis but has not been previously reported to cause orchitis.",2017 Jul 28,"['Piantadosi, Anne', 'Mukerji, Shibani S', 'Chitneni, Pooja', 'Cho, Tracey A', 'Cosimi, Lisa A', 'Hung, Deborah T', 'Goldberg, Marcia B', 'Sabeti, Pardis C', 'Kuritzkes, Daniel R', 'Grad, Yonatan H']",Open Forum Infect Dis,,,False
abd5833ba0f868ce51622b090b9121b3be9c08dc,PMC,Animal models for dengue vaccine development and testing,http://dx.doi.org/10.7774/cevr.2017.6.2.104,PMC5540958,28775974,CC BY-NC,"Dengue fever is a tropical endemic disease; however, because of climate change, it may become a problem in South Korea in the near future. Research on vaccines for dengue fever and outbreak preparedness are currently insufficient. In addition, because there are no appropriate animal models, controversial results from vaccine efficacy assessments and clinical trials have been reported. Therefore, to study the mechanism of dengue fever and test the immunogenicity of vaccines, an appropriate animal model is urgently needed. In addition to mouse models, more suitable models using animals that can be humanized will need to be constructed. In this report, we look at the current status of model animal construction and discuss which models require further development.",2017 Jul 26,"['Na, Woonsung', 'Yeom, Minjoo', 'Choi, Il-Kyu', 'Yook, Heejun', 'Song, Daesub']",Clin Exp Vaccine Res,,,True
839df627ece5b5fc7bb1ce3b4f96127677fd0494,PMC,Preferential production of IgM-secreting hybridomas by immunization with DNA vaccines coding for Ebola virus glycoprotein: use of protein boosting for IgG-secreting hybridoma production,http://dx.doi.org/10.7774/cevr.2017.6.2.135,PMC5540962,28775978,CC BY-NC,"PURPOSE: The goal of this study was to investigate the utility of DNA vaccines encoding Ebola virus glycoprotein (GP) as a vaccine type for the production of GP-specific hybridomas and antibodies. MATERIALS AND METHODS: DNA vaccines were constructed to express Ebola virus GP. Mice were injected with GP DNA vaccines and their splenocytes were used for hybridoma production. Enzyme-linked immunosorbent assays (ELISAs), limiting dilution subcloning, antibody purification methods, and Western blot assays were used to select GP-specific hybridomas and purify monoclonal antibodies (MAbs) from the hybridoma cells. RESULTS: Twelve hybridomas, the cell supernatants of which displayed GP-binding activity, were selected by ELISA. When purified MAbs from 12 hybridomas were tested for their reactivity to GP, 11 MAbs, except for 1 MAb (from the A6-9 hybridoma) displaying an IgG2a type, were identified as IgM isotypes. Those 11 MAbs failed to recognize GP. However, the MAb from A6-9 recognized the mucin-like region of GP and remained reactive to the antigen at the lowest tested concentration (1.95 ng/mL). This result suggests that IgM-secreting hybridomas are predominantly generated by DNA vaccination. However, boosting with GP resulted in greater production of IgG-secreting hybridomas than GP DNA vaccination alone. CONCLUSION: DNA vaccination may preferentially generate IgM-secreting hybridomas, but boosting with the protein antigen can reverse this propensity. Thus, this protein boosting approach may have implications for the production of IgG-specific hybridomas in the context of the DNA vaccination platform. In addition, the purified monoclonal IgG antibodies may be useful as therapeutic antibodies for controlling Ebola virus infection.",2017 Jul 26,"['Lee, Si-Hyeong', 'Han, Baek-Sang', 'Choe, Jongseon', 'Sin, Jeong-Im']",Clin Exp Vaccine Res,,,True
817a885e9613363e08ef920a9e5826a4cb9e1c1e,PMC,Newcastle disease virus vectored vaccines as bivalent or antigen delivery vaccines,http://dx.doi.org/10.7774/cevr.2017.6.2.72,PMC5540967,28775971,CC BY-NC,"Recent advances in reverse genetics techniques make it possible to manipulate the genome of RNA viruses such as Newcastle disease virus (NDV). Several NDV vaccine strains have been used as vaccine vectors in poultry, mammals, and humans to express antigens of different pathogens. The safety, immunogenicity, and protective efficacy of these NDV-vectored vaccines have been evaluated in pre-clinical and clinical studies. The vaccines are safe in mammals, humans, and poultry. Bivalent NDV-vectored vaccines against pathogens of economic importance to the poultry industry have been developed. These bivalent vaccines confer solid protective immunity against NDV and other foreign antigens. In most cases, NDV-vectored vaccines induce strong local and systemic immune responses against the target foreign antigen. This review summarizes the development of NDV-vectored vaccines and their potential use as a base for designing other effective vaccines for veterinary and human use.",2017 Jul 26,"Choi, Kang-Seuk",Clin Exp Vaccine Res,,,True
fce74c6d77b50d5f596c327529665bf89087097c,PMC,Polyethylenimine-based micro/nanoparticles as vaccine adjuvants,http://dx.doi.org/10.2147/IJN.S137980,PMC5546778,28814862,CC BY-NC,"Vaccines have shown great success in treating and preventing tumors and infections, while adjuvants are always demanded to ensure potent immune responses. Polyethylenimine (PEI), as one of the well-studied cationic polymers, has been used as a transfection reagent for decades. However, increasing evidence has shown that PEI-based particles are also capable of acting as adjuvants. In this paper, we briefly review the physicochemical properties and the broad applications of PEI in different fields, and elaborate on the intracellular processes of PEI-based vaccines. In addition, we sum up the proof of their in vivo and clinical applications. We also highlight some mechanisms proposed for the intrinsic immunoactivation function of PEI, followed by the challenges and future perspectives of the applications of PEI in the vaccines, as well as some strategies to elicit the desirable immune responses.",2017 Jul 31,"['Shen, Chen', 'Li, Jun', 'Zhang, Yi', 'Li, Yuce', 'Shen, Guanxin', 'Zhu, Jintao', 'Tao, Juan']",Int J Nanomedicine,,,True
427e9059167b857c57f420d2fd243be87f6b8a33,PMC,A novel cause of chronic viral meningoencephalitis: Cache Valley virus,http://dx.doi.org/10.1002/ana.24982,PMC5546801,28628941,CC BY-NC-ND,"OBJECTIVE: Immunodeficient patients are particularly vulnerable to neuroinvasive infections that can be challenging to diagnose. Metagenomic next generation sequencing can identify unusual or novel microbes and is therefore well suited for investigating the etiology of chronic meningoencephalitis in immunodeficient patients. METHODS: We present the case of a 34‐year‐old man with X‐linked agammaglobulinemia from Australia suffering from 3 years of meningoencephalitis that defied an etiologic diagnosis despite extensive conventional testing, including a brain biopsy. Metagenomic next generation sequencing of his cerebrospinal fluid and brain biopsy tissue was performed to identify a causative pathogen. RESULTS: Sequences aligning to multiple Cache Valley virus genes were identified via metagenomic next generation sequencing. Reverse transcription polymerase chain reaction and immunohistochemistry subsequently confirmed the presence of Cache Valley virus in the brain biopsy tissue. INTERPRETATION: Cache Valley virus, a mosquito‐borne orthobunyavirus, has only been identified in 3 immunocompetent North American patients with acute neuroinvasive disease. The reported severity ranges from a self‐limiting meningitis to a rapidly fatal meningoencephalitis with multiorgan failure. The virus has never been known to cause a chronic systemic or neurologic infection in humans. Cache Valley virus has also never previously been detected on the Australian continent. Our research subject traveled to North and South Carolina and Michigan in the weeks prior to the onset of his illness. This report demonstrates that metagenomic next generation sequencing allows for unbiased pathogen identification, the early detection of emerging viruses as they spread to new locales, and the discovery of novel disease phenotypes. Ann Neurol 2017;82:105–114",2017 Jul 25,"['Wilson, Michael R.', 'Suan, Dan', 'Duggins, Andrew', 'Schubert, Ryan D.', 'Khan, Lillian M.', 'Sample, Hannah A.', 'Zorn, Kelsey C.', 'Rodrigues Hoffman, Aline', 'Blick, Anna', 'Shingde, Meena', 'DeRisi, Joseph L.']",Ann Neurol,,,True
8946e4b778ae5312b4db84cd75b68848c39a3a93,PMC,The Utility of Preliminary Patient Evaluation in a Febrile Respiratory Infectious Disease Unit outside the Emergency Department,http://dx.doi.org/10.3346/jkms.2017.32.9.1534,PMC5546975,28776351,CC BY-NC,"A febrile respiratory infectious disease unit (FRIDU) with a negative pressure ventilation system was constructed outside the emergency department (ED) of the Samsung Medical Center in 2015, to screen for patients with contagious diseases requiring isolation. We evaluated the utility of the FRIDU during 1 year of operation. We analyzed 1,562 patients who were hospitalized after FRIDU screening between August 2015 and July 2016. The level of isolation recommended during their screening at the FRIDU was compared with the level deemed appropriate given their final diagnosis. Of the 1,562 patients screened at the FRIDU, 198 (13%) were isolated, 194 (12%) were reverse isolated, and 1,170 (75%) were not isolated. While hospitalized, 97 patients (6%) were confirmed to have a contagious disease requiring isolation, such as tuberculosis; 207 patients (13%) were confirmed to be immunocompromised and to require reverse isolation, mainly due to neutropenia; and the remaining 1,258 patients (81%) did not require isolation. The correlation coefficient for isolation consistency was 0.565 (P < 0.001). The sensitivity and negative predictive value of FRIDU screening for diagnosing contagious disease requiring isolation are 76% and 98%, respectively. No serious nosocomial outbreaks of contagious diseases occurred. During FRIDU screening, 114 patients were admitted to the resuscitation zone due to clinical instability, and three of these patients died. The initial isolation levels resulting from FRIDU screening were moderately well correlated with the isolation levels required by the final diagnosis, demonstrating the utility of pre-hospitalization screening units. However, the risks of deterioration during the screening process remain challenges.",2017 Sep 3,"['Kang, Jun Sik', 'Jhun, Byung Woo', 'Yoon, Hee', 'Lim, Seong Mi', 'Ko, Eunsil', 'Park, Joo Hyun', 'Hwang, Sung Yeon', 'Lee, Se Uk', 'Lee, Tae Rim', 'Cha, Won Chul', 'Shin, Tae Gun', 'Sim, Min Seob', 'Jo, Ik Joon']",J Korean Med Sci,,,True
300aafb473a32703d4cfab35291a148968bd2749,PMC,The Utility of Preliminary Patient Evaluation in a Febrile Respiratory Infectious Disease Unit outside the Emergency Department,http://dx.doi.org/10.3346/jkms.2017.32.9.1534,PMC5546975,28776351,CC BY-NC,"A febrile respiratory infectious disease unit (FRIDU) with a negative pressure ventilation system was constructed outside the emergency department (ED) of the Samsung Medical Center in 2015, to screen for patients with contagious diseases requiring isolation. We evaluated the utility of the FRIDU during 1 year of operation. We analyzed 1,562 patients who were hospitalized after FRIDU screening between August 2015 and July 2016. The level of isolation recommended during their screening at the FRIDU was compared with the level deemed appropriate given their final diagnosis. Of the 1,562 patients screened at the FRIDU, 198 (13%) were isolated, 194 (12%) were reverse isolated, and 1,170 (75%) were not isolated. While hospitalized, 97 patients (6%) were confirmed to have a contagious disease requiring isolation, such as tuberculosis; 207 patients (13%) were confirmed to be immunocompromised and to require reverse isolation, mainly due to neutropenia; and the remaining 1,258 patients (81%) did not require isolation. The correlation coefficient for isolation consistency was 0.565 (P < 0.001). The sensitivity and negative predictive value of FRIDU screening for diagnosing contagious disease requiring isolation are 76% and 98%, respectively. No serious nosocomial outbreaks of contagious diseases occurred. During FRIDU screening, 114 patients were admitted to the resuscitation zone due to clinical instability, and three of these patients died. The initial isolation levels resulting from FRIDU screening were moderately well correlated with the isolation levels required by the final diagnosis, demonstrating the utility of pre-hospitalization screening units. However, the risks of deterioration during the screening process remain challenges.",2017 Sep 3,"['Kang, Jun Sik', 'Jhun, Byung Woo', 'Yoon, Hee', 'Lim, Seong Mi', 'Ko, Eunsil', 'Park, Joo Hyun', 'Hwang, Sung Yeon', 'Lee, Se Uk', 'Lee, Tae Rim', 'Cha, Won Chul', 'Shin, Tae Gun', 'Sim, Min Seob', 'Jo, Ik Joon']",J Korean Med Sci,,,False
06192007528616a277cecacc4e15d48914e18b8b,PMC,The Utility of Preliminary Patient Evaluation in a Febrile Respiratory Infectious Disease Unit outside the Emergency Department,http://dx.doi.org/10.3346/jkms.2017.32.9.1534,PMC5546975,28776351,CC BY-NC,"A febrile respiratory infectious disease unit (FRIDU) with a negative pressure ventilation system was constructed outside the emergency department (ED) of the Samsung Medical Center in 2015, to screen for patients with contagious diseases requiring isolation. We evaluated the utility of the FRIDU during 1 year of operation. We analyzed 1,562 patients who were hospitalized after FRIDU screening between August 2015 and July 2016. The level of isolation recommended during their screening at the FRIDU was compared with the level deemed appropriate given their final diagnosis. Of the 1,562 patients screened at the FRIDU, 198 (13%) were isolated, 194 (12%) were reverse isolated, and 1,170 (75%) were not isolated. While hospitalized, 97 patients (6%) were confirmed to have a contagious disease requiring isolation, such as tuberculosis; 207 patients (13%) were confirmed to be immunocompromised and to require reverse isolation, mainly due to neutropenia; and the remaining 1,258 patients (81%) did not require isolation. The correlation coefficient for isolation consistency was 0.565 (P < 0.001). The sensitivity and negative predictive value of FRIDU screening for diagnosing contagious disease requiring isolation are 76% and 98%, respectively. No serious nosocomial outbreaks of contagious diseases occurred. During FRIDU screening, 114 patients were admitted to the resuscitation zone due to clinical instability, and three of these patients died. The initial isolation levels resulting from FRIDU screening were moderately well correlated with the isolation levels required by the final diagnosis, demonstrating the utility of pre-hospitalization screening units. However, the risks of deterioration during the screening process remain challenges.",2017 Sep 3,"['Kang, Jun Sik', 'Jhun, Byung Woo', 'Yoon, Hee', 'Lim, Seong Mi', 'Ko, Eunsil', 'Park, Joo Hyun', 'Hwang, Sung Yeon', 'Lee, Se Uk', 'Lee, Tae Rim', 'Cha, Won Chul', 'Shin, Tae Gun', 'Sim, Min Seob', 'Jo, Ik Joon']",J Korean Med Sci,,,False
174f63ff45fc7bbecf0f559200761ad76691b6fb,PMC,Cassiae semen: A review of its phytochemistry and pharmacology,http://dx.doi.org/10.3892/mmr.2017.6880,PMC5547955,28677746,CC BY-NC-ND,"Cassiae semen (Leguminosae), a well-known traditional Chinese medicine, has been used for a number of centuries in areas of Southeast Asia, including Korea, Japan and China. The present review aims to provide updated and comprehensive information, on the botany, phytochemistry and pharmacology of Cassiae semen. The available information on Cassiae semen was collected using several different resources, including classic books on Chinese herbal medicine and a number of scientific databases, including the China Academic Journals full-text database, PubMed, SciFinder, the Web of Science and Science Direct. To date >70 chemical compounds have been isolated from Cassiae semen, and the major components have been determined to be anthraquinones, naphthopyrones and volatile oil. The crude extracts and pure compounds of Cassiae semen have been used as effective agents in preclinical and clinical practice due to their beneficial activities, including antihyperlipidemic, antidiabetic, neuroprotective, hepatoprotective, antibacterial, antioxidant and hypotensive activities. With the body of reported data, it has been suggested that Cassiae semen has convincing medicinal potential. However, the pharmacological mechanisms of the main bioactive compounds and the association between structure and activity require further investigation.",2017 Sep 29,"['Dong, Xiaoxv', 'Fu, Jing', 'Yin, Xingbin', 'Yang, Chunjing', 'Zhang, Xin', 'Wang, Wenping', 'Du, Xueying', 'Wang, Qingling', 'Ni, Jian']",Mol Med Rep,,,True
c506acf42e11fa9de3408fd557799de21ec89080,PMC,ASTHO at 75: Celebrating the Past and Preparing for the Future,http://dx.doi.org/10.1097/PHH.0000000000000629,PMC5548497,28759554,CC BY-NC,,2017 Sep 4,"['Fraser, Michael R.', 'Hardy, George']",J Public Health Manag Pract,,,True
fbdc0117c66b252ed77172829bf245b090ca83f7,PMC,"Evaluation of control measures for bovine viral diarrhea implemented in Nemuro District, Hokkaido, Japan, using a scenario tree model",http://dx.doi.org/10.1292/jvms.17-0108,PMC5559360,28539533,CC BY-NC-ND,"A scenario tree model was developed to propose efficient bovine viral diarrhea (BVD) control measures. The model used field data in eastern Hokkaido where the risk of BVDV infection in cattle has been reduced by an eradication program including mass vaccination, individual tests prior to communal pasture grazing, herd screening tests using bulk milk, and outbreak investigations of newly infected herds. These four activities were then used as hypothesized control measures in the simulation. In each simulation, the numbers of cattle infected persistently and transiently with BVDV detected by clinical manifestations and diagnosis tests and of missed by all of the diagnosis tests were calculated, and the numbers were used as indicators to be compared for the efficacy of the control measures. The model outputs indicated that the adoption of mass vaccination decreased the number of missed BVD cattle, although it did not increase the number of detected BVD cattle. Under implementation of mass vaccination, the efficacy of individual tests on selected 20% of the young and adult cattle was equal to that of the herd screening test performed in all the herds. When the virus prevalence or the number of sensitive animals becomes low, the efficacy of herd screening test was superior to one of individual tests. Considering the model outputs together, the scenario tree model developed in the present study was useful to compare the efficacy of the control measures for BVD.",2017 Jul 25,"['ISODA, Norikazu', 'ASANO, Akihiro', 'ICHIJO, Michiru', 'WAKAMORI, Shiho', 'OHNO, Hiroshi', 'SATO, Kazuhiko', 'OKAMOTO, Hirokazu', 'NAKAO, Shigeru', 'KATO, Hajime', 'SAITO, Kazuma', 'ITO, Naoki', 'USUI, Akira', 'TAKAYAMA, Hiroaki', 'SAKODA, Yoshihiro']",J Vet Med Sci,,,True
60e60278fa8ee4adff6f62b476282a1ea8316f63,PMC,A46 MERS-CoV in Arabian camels in Africa and Central Asia,http://dx.doi.org/10.1093/ve/vew036.045,PMC5565921,28845242,CC BY-NC,,2017 Mar 5,"['Chu, Daniel K.W.', 'Chan, Samuel M.S.', 'Perera, Ranawaka A.P.M.', 'Miguel, Eve', 'Roger, F.', 'Chevalier, V.', 'Poon, Leo L.M.', 'Peiris, Malik']",Virus Evol,,,False
7ce95b9a17a6184e8c9991e8fa57053af683bc05,PMC,"A25 Phylogenetic analysis of the nucleocapsid and RNA-dependent RNA polymerase fragments of the first imported case of middle east respiratory syndrome coronavirus (MERS-CoV) infection in the Philippines from Saudi Arabia, February 2015",http://dx.doi.org/10.1093/ve/vew036.024,PMC5565944,28845258,CC BY-NC,,2017 Mar 5,"['Medado, I.A.P.', 'Orbina, J.R.C.', 'Yabut, N.T.M.', 'Dancel, L.L.M.', 'Tan, T.C.', 'Igoy, M.A.U.', 'Mojica, A.M.R.', 'Lirio, I.C.', 'Ablola, A.C.', 'Mateo, B.C.', 'Biol, M.A.J.', 'Nicolasora, A.D.', 'Morito, H.L.E.', 'Cruz, K.I.M.', 'Roldan, C.M.F.', 'Medina, P.B.', 'Mercado, E.S.', 'Demetria, C.S.', 'Capistrano, R.J.', 'Lupisan, S.P.']",Virus Evol,,,False
95ce22f88f2ccc0f0e7ea58ee33b39e685b22d89,PMC,A24 Application of large-scale sequencing and data analysis to research on emerging infectious diseases,http://dx.doi.org/10.1093/ve/vew036.023,PMC5565992,28845278,CC BY-NC,,2017 Mar 5,"['Liu, Yongmei', 'Lam, Tommy Tsan-Yuk', 'Zhu, Huachen', 'Guan, Yi']",Virus Evol,,,False
d9e6c2b657cc2d3981aed7b10be7d275d7d22518,PMC,A47 Origin and possible genetic recombination of the middle east respiratory syndrome coronavirus from the first imported case in china: phylogenetics and coalescence analysis,http://dx.doi.org/10.1093/ve/vew036.046,PMC5566081,28845291,CC BY-NC,,2017 Mar 5,"['Wang, Yanqun', 'Liu, Di', 'Shi, Weifeng', 'Lu, Roujian', 'Wang, Wenling', 'Zhao, Yanjie', 'Deng, Yao', 'Zhou, Weimin', 'Ren, Hongguang', 'Wu, Jun', 'Wang, Yu', 'Wu, Guizhen', 'Gao, George F.', 'Tan, Wenjie']",Virus Evol,,,False
485f987d1d6344a2982cd356cc2116b4221ad3fe,PMC,Tubuloreticular Inclusions in the Absence of Systemic Lupus Erythematosus and HIV Infection: A Report of Three Pediatric Cases,http://dx.doi.org/10.1159/000477661,PMC5567081,28868299,CC BY-NC,"Tubuloreticular inclusions (TRIs) are subcellular structures located within the cisternae of endoplasmic reticulum. Formation of TRIs has been linked to the exposure of excess interferon (IFN), either from endogenous or exogenous sources. In renal disease, TRIs have been most commonly associated with systemic lupus erythematosus (SLE), and human immunodeficiency virus-associated nephropathy (HIVAN). Case reports of patients with renal biopsies showing TRIs without underlying SLE or HIV are infrequent in adults, and to our knowledge none have been reported in children. We report 3 pediatric cases in which the renal biopsy showed TRIs on electron microscopy without underlying SLE or HIV infection. The first patient presented at 2 years of age with nephrotic syndrome and renal failure. His renal biopsy revealed focal segmental glomerulosclerosis and TRIs. The second patient presented at 6 months of age with infantile nephrotic syndrome, and his renal biopsy revealed membranous glomerulopathy and TRIs. The last patient presented at 4 years of age with acute kidney injury of unclear etiology leading to chronic kidney disease. Her biopsy revealed acute and chronic tubulointerstitial nephritis with TRIs. Despite extensive evaluation in all 3 patients, including testing for HIV infection and SLE, we could not identify an underlying etiology to explain the presence of TRIs. In conclusion, renal biopsy with TRIs in the absence of underling SLE and HIV remains obscure. We propose a possible role for excess IFN triggered by an abnormal immune response to common viral infections in the formation of TRIs and renal injury.",2017 Jun 23,"['Elmaghrabi, Ayah', 'Brown, Elizabeth', 'Khin, Ei', 'Hassler, Jared', 'Hendricks, Allen R.']",Case Rep Nephrol Dial,,,True
f74a10293a7a838fc90185edecb37771cf6cd037,PMC,H7N9 not only endanger human health but also hit stock marketing,http://dx.doi.org/10.25196/adcp201711,PMC5571741,28845481,CC BY-NC-ND,"OBJECTIVE: This study aims to discuss the correlation between daily reported H7N9 cases and stock price indices in China. METHODS: Information on daily reported H7N9 cases and stock market sectors indices between February 19, 2013 and March 31, 2014 were collected. A distributed lag non-linear model was used to describe the variation trend for the stock indices RESULTS: The daily reported number of H7N9 cases was associated with the closing price of the Avian Influenza Sector Index (P < 0.05) and the opening price of the Shanghai Composite Index (P = 0.029). The Avian Influenza Sector Index decreased with increasing of daily reported case number when daily reported cases ≤ 4. Case number was associated with the opening/closing price of the Chinese Traditional Medicine Sector Index, the Biological Product Sector Index, and the Biomedicine Sector Index (P < 0.05). CONCLUSION: New or reemerging infectious diseases epidemic cause economic loss which is reflected in movements in stock prices.",2017 May 30,"['Jiang, Yan', 'Zhang, Yi', 'Ma, Chunna', 'Wang, Quanyi', 'Xu, Chao', 'Donovan, Connor', 'Ali, Gholam', 'Xu, Tan', 'Sun, Wenjie']",Adv Dis Control Prev,,,True
2bd481afbcdbbc5c78d67ed1f7204b09c1f83da1,PMC,Association of Toll-like receptor 2-positive monocytes with coronary artery lesions and treatment nonresponse in Kawasaki disease,http://dx.doi.org/10.3345/kjp.2017.60.7.208,PMC5573743,28861111,CC BY-NC,"PURPOSE: Activation of Toll-like receptor 2 (TLR2) present on circulating monocytes in patients with Kawasaki disease (KD) can lead to the production of proinflammatory cytokines and interleukin-10 (IL-10). We aimed to determine the association of the frequency of circulating TLR2+/CD14+ monocytes (FTLR2%) with the outcomes of KD, as well as to compare FTLR2% to the usefulness of sIL-10. METHODS: The FTLR2% in patients with KD was measured by flow cytometry. Serum levels of IL-10 (sIL-10) were determined in 31 patients with KD before the initial treatment with intravenous immunoglobulin (IVIG) and in 21 febrile controls by using enzyme-linked immunosorbent assay. Patients were classified as having coronary artery lesions (CALs) based on the maximal internal diameters of the proximal right coronary artery and proximal left anterior descending coronary artery one month after the initial diagnosis. RESULTS: We found that FTLR2% greater than 92.62% predicted CALs with 80% sensitivity and 68.4% specificity, whereas FTLR2% more than 94.61% predicted IVIG resistance with 66.7% sensitivity and 71.4% specificity. Moreover, sIL-10 more than 15.52 pg/mL predicted CALs and IVIG resistance with 40% and 66.7% sensitivity, respectively, and 73.7% and 76.2% specificity, respectively. CONCLUSION: We showed that measuring FTLR2% before the initial treatment could be useful in predicting CAL development with better sensitivity than sIL-10 and with results comparable to sIL-10 results for the prediction of IVIG resistance in patients with KD. However, further studies are necessary to validate FTLR2% as a marker of prognosis and severity of KD.",2017 Jul 31,"['Kang, Soo Jung', 'Kim, Nam Su']",Korean J Pediatr,,,True
f3cb4102ee8c1aeb8e68595843292801a08effe3,PMC,"Pandemics, Severity, and Context—Some Loose Ends",http://dx.doi.org/10.1089/hs.2017.0055,PMC5576205,28741964,CC BY-NC,,2017 Aug 1,"['Simonsen, Lone', 'Viboud, Cecile']",Health Secur,,,True
d15a835aad13d6a65a3a7357d321d751914d616a,PMC,Preface,http://dx.doi.org/10.4142/jvs.2017.18.S1.261,PMC5583412,,CC BY-NC,,2017 Aug 22,"['Yoo, Han Sang', 'Ryu, Pan Dong']",J Vet Sci,,,False
550738a7abf0b8378627958a3a5c429f36586d69,PMC,"Optimization of human, animal, and environmental health by using the One Health approach",http://dx.doi.org/10.4142/jvs.2017.18.S1.263,PMC5583413,28859266,CC BY-NC,"Emerging diseases are increasing burdens on public health, negatively affecting the world economy, causing extinction of species, and disrupting ecological integrity. One Health recognizes that human, domestic animal, and wildlife health are interconnected within ecosystem health and provides a framework for the development of multidisciplinary solutions to global health challenges. To date, most health-promoting interventions have focused largely on single-sector outcomes. For example, risk for transmission of zoonotic pathogens from bush-meat hunting is primarily focused on human hygiene and personal protection. However, bush-meat hunting is a complex issue promoting the need for holistic strategies to reduce transmission of zoonotic disease while addressing food security and wildlife conservation issues. Temporal and spatial separation of humans and wildlife, risk communication, and other preventative strategies should allow wildlife and humans to co-exist. Upstream surveillance, vaccination, and other tools to prevent pathogen spillover are also needed. Clear multi-sector outcomes should be defined, and a systems-based approach is needed to develop interventions that reduce risks and balance the needs of humans, wildlife, and the environment. The ultimate goal is long-term action to reduce forces driving emerging diseases and provide interdisciplinary scientific approaches to management of risks, thereby achieving optimal outcomes for human, animal, and environmental health.",2017 Aug 22,"['Sleeman, Jonathan M.', 'DeLiberto, Thomas', 'Nguyen, Natalie']",J Vet Sci,,,True
def69723f3ff30495aab9e155921db015a6aac41,PMC,Establishment of minimal positive-control conditions to ensure brain safety during rapid development of emergency vaccines,http://dx.doi.org/10.4142/jvs.2017.18.S1.371,PMC5583425,28859273,CC BY-NC,"With the increase in international human and material exchanges, contagious and infectious epidemics are occurring. One of the effective methods of epidemic inhibition is the rapid development and supply of vaccines. Considering the safety of the brain during vaccine development is very important. However, manuals for brain safety assays for new vaccines are not uniform or effective globally. Therefore, the aim of this study is to establish a positive-control protocol for an effective brain safety test to enhance rapid vaccine development. The blood-brain barrier's tight junctions provide selective defense of the brain; however, it is possible to destroy these important microstructures by administering lipopolysaccharides (LPSs), thereby artificially increasing the permeability of brain parenchyma. In this study, test conditions are established so that the degree of brain penetration or brain destruction of newly developed vaccines can be quantitatively identified. The most effective conditions were suggested by measuring time-dependent expressions of tight junction biomarkers (zonula occludens-1 [ZO-1] and occludin) in two types of mice (C57BL/6 and ICR) following exposure to two types of LPS (Salmonella and Escherichia). In the future, we hope that use of the developed positive-control protocol will help speed up the determination of brain safety of novel vaccines.",2017 Aug 22,"['Baek, Hyekyung', 'Kim, Kwang Ho', 'Park, Min Young', 'Kim, Kyeongryun', 'Ko, Bokyeong', 'Seo, Hyung Seok', 'Kim, Byoung Soo', 'Hahn, Tae-Wook', 'Yi, Sun Shin']",J Vet Sci,,,True
66ee6c750afeb7f2f0ae49100a5b3c08f91dc2bf,PMC,Systems Vaccinology Identifies an Early Innate Immune Signature as a Correlate of Antibody Responses to the Ebola Vaccine rVSV-ZEBOV,http://dx.doi.org/10.1016/j.celrep.2017.08.023,PMC5583508,28854372,CC BY-NC-ND,"Predicting vaccine efficacy remains a challenge. We used a systems vaccinology approach to identify early innate immune correlates of antibody induction in humans receiving the Ebola vaccine rVSV-ZEBOV. Blood samples from days 0, 1, 3, 7, and 14 were analyzed for changes in cytokine levels, innate immune cell subsets, and gene expression. Integrative statistical analyses with cross-validation identified a signature of 5 early innate markers correlating with antibody titers on day 28 and beyond. Among those, IP-10 on day 3 and MFI of CXCR6 on NK cells on day 1 were independent correlates. Consistently, we found an early gene expression signature linked to IP-10. This comprehensive characterization of early innate immune responses to the rVSV-ZEBOV vaccine in humans revealed immune signatures linked to IP-10. These results suggest correlates of vaccine-induced antibody induction and provide a rationale to explore strategies for augmenting the effectiveness of vaccines through manipulation of IP-10.",2017 Aug 29,"['Rechtien, Anne', 'Richert, Laura', 'Lorenzo, Hadrien', 'Martrus, Gloria', 'Hejblum, Boris', 'Dahlke, Christine', 'Kasonta, Rahel', 'Zinser, Madeleine', 'Stubbe, Hans', 'Matschl, Urte', 'Lohse, Ansgar', 'Krähling, Verena', 'Eickmann, Markus', 'Becker, Stephan', None, 'Thiébaut, Rodolphe', 'Altfeld, Marcus', 'Addo, Marylyn']",Cell Rep,,,False
c8e37f08a80fe7f78bcb5ca1e9598bc65c470d07,PMC,Systems Vaccinology Identifies an Early Innate Immune Signature as a Correlate of Antibody Responses to the Ebola Vaccine rVSV-ZEBOV,http://dx.doi.org/10.1016/j.celrep.2017.08.023,PMC5583508,28854372,CC BY-NC-ND,"Predicting vaccine efficacy remains a challenge. We used a systems vaccinology approach to identify early innate immune correlates of antibody induction in humans receiving the Ebola vaccine rVSV-ZEBOV. Blood samples from days 0, 1, 3, 7, and 14 were analyzed for changes in cytokine levels, innate immune cell subsets, and gene expression. Integrative statistical analyses with cross-validation identified a signature of 5 early innate markers correlating with antibody titers on day 28 and beyond. Among those, IP-10 on day 3 and MFI of CXCR6 on NK cells on day 1 were independent correlates. Consistently, we found an early gene expression signature linked to IP-10. This comprehensive characterization of early innate immune responses to the rVSV-ZEBOV vaccine in humans revealed immune signatures linked to IP-10. These results suggest correlates of vaccine-induced antibody induction and provide a rationale to explore strategies for augmenting the effectiveness of vaccines through manipulation of IP-10.",2017 Aug 29,"['Rechtien, Anne', 'Richert, Laura', 'Lorenzo, Hadrien', 'Martrus, Gloria', 'Hejblum, Boris', 'Dahlke, Christine', 'Kasonta, Rahel', 'Zinser, Madeleine', 'Stubbe, Hans', 'Matschl, Urte', 'Lohse, Ansgar', 'Krähling, Verena', 'Eickmann, Markus', 'Becker, Stephan', None, 'Thiébaut, Rodolphe', 'Altfeld, Marcus', 'Addo, Marylyn']",Cell Rep,,,False
0f93d30fe8e5f0277c822d5cbc8c04cb5bb60d41,PMC,Systems Vaccinology Identifies an Early Innate Immune Signature as a Correlate of Antibody Responses to the Ebola Vaccine rVSV-ZEBOV,http://dx.doi.org/10.1016/j.celrep.2017.08.023,PMC5583508,28854372,CC BY-NC-ND,"Predicting vaccine efficacy remains a challenge. We used a systems vaccinology approach to identify early innate immune correlates of antibody induction in humans receiving the Ebola vaccine rVSV-ZEBOV. Blood samples from days 0, 1, 3, 7, and 14 were analyzed for changes in cytokine levels, innate immune cell subsets, and gene expression. Integrative statistical analyses with cross-validation identified a signature of 5 early innate markers correlating with antibody titers on day 28 and beyond. Among those, IP-10 on day 3 and MFI of CXCR6 on NK cells on day 1 were independent correlates. Consistently, we found an early gene expression signature linked to IP-10. This comprehensive characterization of early innate immune responses to the rVSV-ZEBOV vaccine in humans revealed immune signatures linked to IP-10. These results suggest correlates of vaccine-induced antibody induction and provide a rationale to explore strategies for augmenting the effectiveness of vaccines through manipulation of IP-10.",2017 Aug 29,"['Rechtien, Anne', 'Richert, Laura', 'Lorenzo, Hadrien', 'Martrus, Gloria', 'Hejblum, Boris', 'Dahlke, Christine', 'Kasonta, Rahel', 'Zinser, Madeleine', 'Stubbe, Hans', 'Matschl, Urte', 'Lohse, Ansgar', 'Krähling, Verena', 'Eickmann, Markus', 'Becker, Stephan', None, 'Thiébaut, Rodolphe', 'Altfeld, Marcus', 'Addo, Marylyn']",Cell Rep,,,False
7688b1a7662e60226e0011fe6262f6d9114e1906,PMC,Synthetic Biology and Personalized Medicine,http://dx.doi.org/10.1159/000341794,PMC5586729,22907209,CC BY-NC,"Synthetic biology, application of synthetic chemistry to biology, is a broad term that covers the engineering of biological systems with structures and functions not found in nature to process information, manipulate chemicals, produce energy, maintain cell environment and enhance human health. Synthetic biology devices contribute not only to improve our understanding of disease mechanisms, but also provide novel diagnostic tools. Methods based on synthetic biology enable the design of novel strategies for the treatment of cancer, immune diseases metabolic disorders and infectious diseases as well as the production of cheap drugs. The potential of synthetic genome, using an expanded genetic code that is designed for specific drug synthesis as well as delivery and activation of the drug in vivo by a pathological signal, was already pointed out during a lecture delivered at Kuwait University in 2005. Of two approaches to synthetic biology, top-down and bottom-up, the latter is more relevant to the development of personalized medicines as it provides more flexibility in constructing a partially synthetic cell from basic building blocks for a desired task.",2013 Mar 16,"Jain, K.K.",Med Princ Pract,,,True
f92cd3c86281eee402ab60a75990ae6bb57b3c35,PMC,Performance Evaluation of the PowerChek MERS (upE & ORF1a) Real-Time PCR Kit for the Detection of Middle East Respiratory Syndrome Coronavirus RNA,http://dx.doi.org/10.3343/alm.2017.37.6.494,PMC5587821,28840986,CC BY-NC,"BACKGROUND: Molecular detection of Middle East respiratory syndrome coronavirus (MERS-CoV) using real-time reverse transcription (rRT)-PCR assays is the method of choice for diagnosis of MERS. We evaluated the performance of the PowerChek MERS (upE & ORF1a) real-time PCR Kit (PowerChek MERS assay; Kogene Biotech, Korea) a one-step rRT-PCR assay for the qualitative detection of MERS-CoV. METHODS: We evaluated PowerChek MERS assay performance in comparison with nested RT-PCR and sequencing of the RNA-dependent RNA polymerase (RdRp) and N genes. To evaluate diagnostic sensitivity and specificity, 100 clinical specimens (50 positive and 50 negative for MERS-CoV) were simultaneously tested by using the PowerChek MERS and sequencing assays. Assay performance, including limit of detection and precision, was evaluated in vitro by using MERS-CoV RNA transcripts. Analytical specificity was evaluated with a diverse collection of 16 respiratory virus–positive clinical specimens and 14 respiratory bacterial isolates. RESULTS: The 95% limits of detection of the PowerChek MERS assay for the upE and the open rading frame (ORF)1a were 16.2 copies/µL and 8.2 copies/µL, respectively. No cross-reactivity was observed. The diagnostic sensitivity and specificity of the PowerChek MERS assay were both 100% (95% confidence interval, 91.1–100%). CONCLUSIONS: The PowerChek MERS assay is a straightforward and accurate assay for detecting MERS-CoV RNA. The assay will be a useful tool for the rapid diagnosis of MERS and could prove especially important for MERS outbreak control.",2017 Nov 16,"['Huh, Hee Jae', 'Kim, Ji-Youn', 'Kwon, Hyeon Jeong', 'Yun, Sun Ae', 'Lee, Myoung-Keun', 'Ki, Chang-Seok', 'Lee, Nam Yong', 'Kim, Jong-Won']",Ann Lab Med,,,True
3b299c75b42f7b4119456256518d2d8753d74838,PMC,"The Prevalence of Human Bocavirus, Human Coronavirus-NL63, Human Metapneumovirus, Human Polyomavirus KI and WU in Respiratory Tract Infections in Kuwait",http://dx.doi.org/10.1159/000381422,PMC5588235,25925246,CC BY-NC,"OBJECTIVE: The aim of this study was to investigate the prevalence of human coronavirus (HCoV)-NL63, human metapneumovirus (hMPV), human bocavirus (Boca), human polyomavirus KI (KIV) and human polyomavirus WU (WUV) in respiratory tract infections (RTI) in Kuwait. MATERIALS AND METHODS: Respiratory samples from 735 hospitalized patients with RTI from September 2010 to April 2013 were evaluated for the presence of HCoV-NL63, hMPV, Boca, KIV and WUV using molecular assays, polymerase chain reaction (PCR) and reverse-transcription PCR. RESULTS: Of the 735 patients, 285 (38.8%) were diagnosed with viral RTI. The distribution of respiratory viruses was hMPV: 15 (5.3%), Boca: 14 (4.9%), WUV: 10 (3.5%) and KIV: 4 (1.4%). HCoV-NL63 was not detected in any of the samples. CONCLUSIONS: These newly discovered viruses were associated with the development of RTI in Kuwait. The rapid identification of these viral infections could aid in the control of nosocomial transmission, reduce the use of antibiotics and improve treatment and management strategies.",2015 Jun 24,"['Essa, Sahar', 'Owayed, Abdullah', 'Altawalah, Haya', 'Khadadah, Mousa', 'Behbehani, Nasser', 'Al-Nakib, Widad']",Med Princ Pract,,,True
1713cd0fd51641af87b70af84cd2b80227538871,PMC,"Contents Vol. 24, 2015",http://dx.doi.org/10.1159/000441341,PMC5588286,,CC BY-NC,,2015 Oct 23,,Med Princ Pract,,,False
485169c3d48f25be33434505f0e9b5ea5c1256f9,PMC,Identification of an enterovirus recombinant with a torovirus-like gene insertion during a diarrhea outbreak in fattening pigs,http://dx.doi.org/10.1093/ve/vex024,PMC5591953,28924489,CC BY-NC,"Diarrhea outbreaks in pig farms have raised major concerns in Europe and USA, as they can lead to dramatic pig losses. During a suspected outbreak in Belgium of porcine epidemic diarrhea virus (PEDV), we performed viral metagenomics to assess other potential viral pathogens. Although PEDV was detected, its low abundance indicated that other viruses were involved in the outbreak. Interestingly, a porcine bocavirus and several enteroviruses were most abundant in the sample. We also observed the presence of a porcine enterovirus genome with a gene insertion, resembling a C28 peptidase gene found in toroviruses, which was confirmed using re-sequencing, bioinformatics, and proteomics approaches. Moreover, the predicted cleavage sites for the insertion suggest that this gene was being expressed as a single protein, rather than a fused protein. Recombination in enteroviruses has been reported as a major mechanism to generate genetic diversity, but gene insertions across viral families are rather uncommon. Although such inter-family recombinations are rare, our finding suggests that these events may significantly contribute to viral evolution.",2017 Sep 8,"['Conceição-Neto, Nádia', 'Theuns, Sebastiaan', 'Cui, Tingting', 'Zeller, Mark', 'Yinda, Claude Kwe', 'Christiaens, Isaura', 'Heylen, Elisabeth', 'Van Ranst, Marc', 'Carpentier, Sebastien', 'Nauwynck, Hans J.', 'Matthijnssens, Jelle']",Virus Evol,,,True
e86d708c33810a5f18f82a52a3cebfb82c46f716,PMC,Identification of an enterovirus recombinant with a torovirus-like gene insertion during a diarrhea outbreak in fattening pigs,http://dx.doi.org/10.1093/ve/vex024,PMC5591953,28924489,CC BY-NC,"Diarrhea outbreaks in pig farms have raised major concerns in Europe and USA, as they can lead to dramatic pig losses. During a suspected outbreak in Belgium of porcine epidemic diarrhea virus (PEDV), we performed viral metagenomics to assess other potential viral pathogens. Although PEDV was detected, its low abundance indicated that other viruses were involved in the outbreak. Interestingly, a porcine bocavirus and several enteroviruses were most abundant in the sample. We also observed the presence of a porcine enterovirus genome with a gene insertion, resembling a C28 peptidase gene found in toroviruses, which was confirmed using re-sequencing, bioinformatics, and proteomics approaches. Moreover, the predicted cleavage sites for the insertion suggest that this gene was being expressed as a single protein, rather than a fused protein. Recombination in enteroviruses has been reported as a major mechanism to generate genetic diversity, but gene insertions across viral families are rather uncommon. Although such inter-family recombinations are rare, our finding suggests that these events may significantly contribute to viral evolution.",2017 Sep 8,"['Conceição-Neto, Nádia', 'Theuns, Sebastiaan', 'Cui, Tingting', 'Zeller, Mark', 'Yinda, Claude Kwe', 'Christiaens, Isaura', 'Heylen, Elisabeth', 'Van Ranst, Marc', 'Carpentier, Sebastien', 'Nauwynck, Hans J.', 'Matthijnssens, Jelle']",Virus Evol,,,False
fd32b4b3e0a8b1b81829faee081dc74bbf299aa5,PMC,Identification of an enterovirus recombinant with a torovirus-like gene insertion during a diarrhea outbreak in fattening pigs,http://dx.doi.org/10.1093/ve/vex024,PMC5591953,28924489,CC BY-NC,"Diarrhea outbreaks in pig farms have raised major concerns in Europe and USA, as they can lead to dramatic pig losses. During a suspected outbreak in Belgium of porcine epidemic diarrhea virus (PEDV), we performed viral metagenomics to assess other potential viral pathogens. Although PEDV was detected, its low abundance indicated that other viruses were involved in the outbreak. Interestingly, a porcine bocavirus and several enteroviruses were most abundant in the sample. We also observed the presence of a porcine enterovirus genome with a gene insertion, resembling a C28 peptidase gene found in toroviruses, which was confirmed using re-sequencing, bioinformatics, and proteomics approaches. Moreover, the predicted cleavage sites for the insertion suggest that this gene was being expressed as a single protein, rather than a fused protein. Recombination in enteroviruses has been reported as a major mechanism to generate genetic diversity, but gene insertions across viral families are rather uncommon. Although such inter-family recombinations are rare, our finding suggests that these events may significantly contribute to viral evolution.",2017 Sep 8,"['Conceição-Neto, Nádia', 'Theuns, Sebastiaan', 'Cui, Tingting', 'Zeller, Mark', 'Yinda, Claude Kwe', 'Christiaens, Isaura', 'Heylen, Elisabeth', 'Van Ranst, Marc', 'Carpentier, Sebastien', 'Nauwynck, Hans J.', 'Matthijnssens, Jelle']",Virus Evol,,,False
4b6e7a4c9c70928f1e2f25994c6d7cfb38178d7d,PMC,Identification of an enterovirus recombinant with a torovirus-like gene insertion during a diarrhea outbreak in fattening pigs,http://dx.doi.org/10.1093/ve/vex024,PMC5591953,28924489,CC BY-NC,"Diarrhea outbreaks in pig farms have raised major concerns in Europe and USA, as they can lead to dramatic pig losses. During a suspected outbreak in Belgium of porcine epidemic diarrhea virus (PEDV), we performed viral metagenomics to assess other potential viral pathogens. Although PEDV was detected, its low abundance indicated that other viruses were involved in the outbreak. Interestingly, a porcine bocavirus and several enteroviruses were most abundant in the sample. We also observed the presence of a porcine enterovirus genome with a gene insertion, resembling a C28 peptidase gene found in toroviruses, which was confirmed using re-sequencing, bioinformatics, and proteomics approaches. Moreover, the predicted cleavage sites for the insertion suggest that this gene was being expressed as a single protein, rather than a fused protein. Recombination in enteroviruses has been reported as a major mechanism to generate genetic diversity, but gene insertions across viral families are rather uncommon. Although such inter-family recombinations are rare, our finding suggests that these events may significantly contribute to viral evolution.",2017 Sep 8,"['Conceição-Neto, Nádia', 'Theuns, Sebastiaan', 'Cui, Tingting', 'Zeller, Mark', 'Yinda, Claude Kwe', 'Christiaens, Isaura', 'Heylen, Elisabeth', 'Van Ranst, Marc', 'Carpentier, Sebastien', 'Nauwynck, Hans J.', 'Matthijnssens, Jelle']",Virus Evol,,,False
c1beebff4b968490702ce4934b92d0cf8520b20e,PMC,Identification of an enterovirus recombinant with a torovirus-like gene insertion during a diarrhea outbreak in fattening pigs,http://dx.doi.org/10.1093/ve/vex024,PMC5591953,28924489,CC BY-NC,"Diarrhea outbreaks in pig farms have raised major concerns in Europe and USA, as they can lead to dramatic pig losses. During a suspected outbreak in Belgium of porcine epidemic diarrhea virus (PEDV), we performed viral metagenomics to assess other potential viral pathogens. Although PEDV was detected, its low abundance indicated that other viruses were involved in the outbreak. Interestingly, a porcine bocavirus and several enteroviruses were most abundant in the sample. We also observed the presence of a porcine enterovirus genome with a gene insertion, resembling a C28 peptidase gene found in toroviruses, which was confirmed using re-sequencing, bioinformatics, and proteomics approaches. Moreover, the predicted cleavage sites for the insertion suggest that this gene was being expressed as a single protein, rather than a fused protein. Recombination in enteroviruses has been reported as a major mechanism to generate genetic diversity, but gene insertions across viral families are rather uncommon. Although such inter-family recombinations are rare, our finding suggests that these events may significantly contribute to viral evolution.",2017 Sep 8,"['Conceição-Neto, Nádia', 'Theuns, Sebastiaan', 'Cui, Tingting', 'Zeller, Mark', 'Yinda, Claude Kwe', 'Christiaens, Isaura', 'Heylen, Elisabeth', 'Van Ranst, Marc', 'Carpentier, Sebastien', 'Nauwynck, Hans J.', 'Matthijnssens, Jelle']",Virus Evol,,,False
8816b524c80d6139fc841eb5f85ff6e97c361181,PMC,Identification of an enterovirus recombinant with a torovirus-like gene insertion during a diarrhea outbreak in fattening pigs,http://dx.doi.org/10.1093/ve/vex024,PMC5591953,28924489,CC BY-NC,"Diarrhea outbreaks in pig farms have raised major concerns in Europe and USA, as they can lead to dramatic pig losses. During a suspected outbreak in Belgium of porcine epidemic diarrhea virus (PEDV), we performed viral metagenomics to assess other potential viral pathogens. Although PEDV was detected, its low abundance indicated that other viruses were involved in the outbreak. Interestingly, a porcine bocavirus and several enteroviruses were most abundant in the sample. We also observed the presence of a porcine enterovirus genome with a gene insertion, resembling a C28 peptidase gene found in toroviruses, which was confirmed using re-sequencing, bioinformatics, and proteomics approaches. Moreover, the predicted cleavage sites for the insertion suggest that this gene was being expressed as a single protein, rather than a fused protein. Recombination in enteroviruses has been reported as a major mechanism to generate genetic diversity, but gene insertions across viral families are rather uncommon. Although such inter-family recombinations are rare, our finding suggests that these events may significantly contribute to viral evolution.",2017 Sep 8,"['Conceição-Neto, Nádia', 'Theuns, Sebastiaan', 'Cui, Tingting', 'Zeller, Mark', 'Yinda, Claude Kwe', 'Christiaens, Isaura', 'Heylen, Elisabeth', 'Van Ranst, Marc', 'Carpentier, Sebastien', 'Nauwynck, Hans J.', 'Matthijnssens, Jelle']",Virus Evol,,,False
cb7c0d2e7a6a79bf12eeed3d17d0d47f338f63ae,PMC,Identification of an enterovirus recombinant with a torovirus-like gene insertion during a diarrhea outbreak in fattening pigs,http://dx.doi.org/10.1093/ve/vex024,PMC5591953,28924489,CC BY-NC,"Diarrhea outbreaks in pig farms have raised major concerns in Europe and USA, as they can lead to dramatic pig losses. During a suspected outbreak in Belgium of porcine epidemic diarrhea virus (PEDV), we performed viral metagenomics to assess other potential viral pathogens. Although PEDV was detected, its low abundance indicated that other viruses were involved in the outbreak. Interestingly, a porcine bocavirus and several enteroviruses were most abundant in the sample. We also observed the presence of a porcine enterovirus genome with a gene insertion, resembling a C28 peptidase gene found in toroviruses, which was confirmed using re-sequencing, bioinformatics, and proteomics approaches. Moreover, the predicted cleavage sites for the insertion suggest that this gene was being expressed as a single protein, rather than a fused protein. Recombination in enteroviruses has been reported as a major mechanism to generate genetic diversity, but gene insertions across viral families are rather uncommon. Although such inter-family recombinations are rare, our finding suggests that these events may significantly contribute to viral evolution.",2017 Sep 8,"['Conceição-Neto, Nádia', 'Theuns, Sebastiaan', 'Cui, Tingting', 'Zeller, Mark', 'Yinda, Claude Kwe', 'Christiaens, Isaura', 'Heylen, Elisabeth', 'Van Ranst, Marc', 'Carpentier, Sebastien', 'Nauwynck, Hans J.', 'Matthijnssens, Jelle']",Virus Evol,,,False
76cbada4dbb0c067cbffac6a1f1cede25aec708b,PMC,The Impact of Middle East Respiratory Syndrome Outbreak on Trends in Emergency Department Utilization Patterns,http://dx.doi.org/10.3346/jkms.2017.32.10.1576,PMC5592169,28875599,CC BY-NC,"Changes occurred in the patterns of utilization of emergency medical services during the Middle East respiratory syndrome (MERS) outbreak. The purpose of this study was to analyze the patterns of adult and pediatric patients who visited the emergency department (ED) during the outbreak. This retrospective study was conducted by analyzing changes in the patterns of visits among adult and pediatric patients in the ED at one tertiary teaching hospital in Korea. The study was performed from June 1, 2013 to July 31, 2015. The MERS outbreak period was from June 1 to July 31, 2015, and we compared that period to the same periods in 2013 and 2014. We compared and analyzed the patients' characteristics, emergency severity index (ESI) level at the visit, cause of visit, diagnosis, final dispositions, injury/non-injury, length of stay at the ED (EDLOS), and hospitalization rate. A total of 9,107 patients visited the ED during this period. Of these patients, 2,572 (28.2%) were pediatric patients and 6,535 (71.8%) were adult patients. The most common cause of an ED visit was fever (adult patients: 21.6%, pediatric patients: 56.2%). The proportion of non-urgent visits involving an ESI level of 4 or 5 and the EDLOS decreased significantly in pediatric and adult patients in comparison to that during the past two years. This change was significant in pediatric patients. Among adult patients, the rate of injury decreased, whereas it increased among pediatric patients. During the MERS outbreak period, pediatric ED visits due to non-urgent cases decreased significantly and there were more pronounced differences in ED utilization patterns in pediatric patients than in adult patients.",2017 Oct 4,"['Paek, So Hyun', 'Kim, Do Kyun', 'Lee, Jin Hee', 'Kwak, Young Ho']",J Korean Med Sci,,,True
2808175f20e87931b354d8b6d623abf8e338fb14,PMC,The Impact of Middle East Respiratory Syndrome Outbreak on Trends in Emergency Department Utilization Patterns,http://dx.doi.org/10.3346/jkms.2017.32.10.1576,PMC5592169,28875599,CC BY-NC,"Changes occurred in the patterns of utilization of emergency medical services during the Middle East respiratory syndrome (MERS) outbreak. The purpose of this study was to analyze the patterns of adult and pediatric patients who visited the emergency department (ED) during the outbreak. This retrospective study was conducted by analyzing changes in the patterns of visits among adult and pediatric patients in the ED at one tertiary teaching hospital in Korea. The study was performed from June 1, 2013 to July 31, 2015. The MERS outbreak period was from June 1 to July 31, 2015, and we compared that period to the same periods in 2013 and 2014. We compared and analyzed the patients' characteristics, emergency severity index (ESI) level at the visit, cause of visit, diagnosis, final dispositions, injury/non-injury, length of stay at the ED (EDLOS), and hospitalization rate. A total of 9,107 patients visited the ED during this period. Of these patients, 2,572 (28.2%) were pediatric patients and 6,535 (71.8%) were adult patients. The most common cause of an ED visit was fever (adult patients: 21.6%, pediatric patients: 56.2%). The proportion of non-urgent visits involving an ESI level of 4 or 5 and the EDLOS decreased significantly in pediatric and adult patients in comparison to that during the past two years. This change was significant in pediatric patients. Among adult patients, the rate of injury decreased, whereas it increased among pediatric patients. During the MERS outbreak period, pediatric ED visits due to non-urgent cases decreased significantly and there were more pronounced differences in ED utilization patterns in pediatric patients than in adult patients.",2017 Oct 4,"['Paek, So Hyun', 'Kim, Do Kyun', 'Lee, Jin Hee', 'Kwak, Young Ho']",J Korean Med Sci,,,False
34a942268ef93e2776d5074b3fb75879858712b6,PMC,MERS-CoV Infection in a Pregnant Woman in Korea,http://dx.doi.org/10.3346/jkms.2017.32.10.1717,PMC5592190,28875620,CC BY-NC,"Middle East respiratory syndrome (MERS) is a lethal respiratory disease — caused by MERS-coronavirus (MERS-CoV) which was first identified in 2012. Especially, pregnant women can be expected as highly vulnerable candidates for this viral infection. In May 2015, this virus was spread in Korea and a pregnant woman was confirmed with positive result of MERS-CoV polymerase chain reaction (PCR). Her condition was improved only with conservative treatment. After a full recovery of MERS, the patient manifested abrupt vaginal bleeding with rupture of membrane. Under an impression of placenta abruption, an emergent cesarean section was performed. Our team performed many laboratory tests related to MERS-CoV and all results were negative. We report the first case of MERS-CoV infection during pregnancy occurred outside of the Middle East. Also, this case showed relatively benign maternal course which resulted in full recovery with subsequent healthy full-term delivery without MERS-CoV transmission.",2017 Oct 8,"['Jeong, Soo Young', 'Sung, Se In', 'Sung, Ji-Hee', 'Ahn, So Yoon', 'Kang, Eun-Suk', 'Chang, Yun Sil', 'Park, Won Soon', 'Kim, Jong-Hwa']",J Korean Med Sci,,,True
c7a16d3975bbb4ad4f44786d1e5961d16d21f863,PMC,Clinicopathologic Features and Magnetic Resonance Imaging Findings in 24 Cats With Histopathologically Confirmed Neurologic Feline Infectious Peritonitis,http://dx.doi.org/10.1111/jvim.14791,PMC5598904,28833469,CC BY-NC,"BACKGROUND: Feline infectious peritonitis (FIP) is the most common infectious central nervous system (CNS) disease in the cat and is invariably fatal. Improved means of antemortem diagnosis is required to facilitate clinical decision making. Information regarding the magnetic resonance imaging (MRI) findings of neurologic FIP currently is limited, resulting in the need for better descriptions to optimize its use as a diagnostic tool. OBJECTIVE: To describe the clinicopathologic features and MRI findings in cases of confirmed neurologic FIP. ANIMALS: Twenty‐four client‐owned cats with histopathologic confirmation of neurologic FIP. METHODS: Archived records from 5 institutions were retrospectively reviewed to identify cases with confirmed neurologic FIP that had undergone antemortem MRI of the CNS. Signalment, clinicopathologic, MRI, and histopathologic findings were evaluated. RESULTS: Three distinct clinical syndromes were identified: T3‐L3 myelopathy (3), central vestibular syndrome (7), and multifocal CNS disease (14). Magnetic resonance imaging abnormalities were detected in all cases, including meningeal contrast enhancement (22), ependymal contrast enhancement (20), ventriculomegaly (20), syringomyelia (17), and foramen magnum herniation (14). Cerebrospinal fluid was analysed in 11 cases; all demonstrated a marked increase in total protein concentration and total nucleated cell count. All 24 cats were euthanized with a median survival time of 14 days (range, 2–115) from onset of clinical signs. Histopathologic analysis identified perivascular pyogranulomatous infiltrates, lymphoplasmacytic infiltrates, or both affecting the leptomeninges (16), choroid plexuses (16), and periventricular parenchyma (13). CONCLUSIONS AND CLINICAL IMPORTANCE: Magnetic resonance imaging is a sensitive means of detecting neurologic FIP, particularly in combination with a compatible signalment, clinical presentation, and CSF analysis.",2017 Aug 19 Sep-Oct,"['Crawford, A.H.', 'Stoll, A.L.', 'Sanchez‐Masian, D.', 'Shea, A.', 'Michaels, J.', 'Fraser, A.R.', 'Beltran, E.']",J Vet Intern Med,,,True
db94e7aa6b683896a9ff5a239003a0c351f60041,PMC,Prevalence of Respiratory Viral Infections in Korean Adult Asthmatics With Acute Exacerbations: Comparison With Those With Stable State,http://dx.doi.org/10.4168/aair.2017.9.6.491,PMC5603477,28913988,CC BY-NC,"PURPOSE: Viral infections are involved in ~50% of exacerbations among Caucasian adult asthmatics. However, there have been few reports on the causative virus of exacerbations in Korean adult asthmatics. Thus, we compared frequencies and types of viruses between lower respiratory tract illnesses (LRTIs) with exacerbations (exacerbated LRTIs) and those without exacerbations (stable LRTIs) to evaluate contribution of respiratory viruses to exacerbations. METHODS: Viral RNA was extracted from sputum using the Viral Gene-spin™ Kit. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect adenovirus (ADV), metapneumovirus (MPV), parainfluenza virus (PIV) 1/2/3, influenza virus (IFV) A, IFV B, respiratory syncytial virus (RSV) A/B, and rhinovirus (RV) A. RESULTS: Among the 259 patients, 210 underwent a single sputum examination, and the remaining 49 underwent 2 to 4 sputum examinations. Virus was detected in 68 of the 259 exacerbated episodes and in 11 of the 64 stable episodes. Among the exacerbated episodes, RV was the most frequently detected virus, followed by influenza A, parainfluenza, RSV A/B, and ADV. Among the 11 stable episodes, RV was most frequently detected. Detection rates of these viruses did not differ between the 2 groups (P>0.05). Thirty-five patients underwent the virus examination at 2 episodes of exacerbation, while 14 patients underwent at each time of exacerbated and stable episodes. Virus detection rate at the second examination was significantly higher in cases with 2 exacerbation episodes than in those with initial exacerbation and sequential stable episodes (P=0.003). A seasonal pattern was noted in the detection rates of RV (September to December), IFV (January to April), PIV (May to September), and RSV A/B (September to April). CONCLUSIONS: Respiratory viruses were identified in approximately 20% of LRTI irrespective of the presence of asthma exacerbation. RV and IFV A/B were most frequently detected. A group of patients experienced frequent viral infections followed by asthma exacerbations.",2017 Nov 4,"['Seo, Ki-Hyun', 'Bae, Da-Jeong', 'Kim, Ji-Na', 'Lee, Ho-Sung', 'Kim, Yong-Hoon', 'Park, Jong-Sook', 'Kim, Myung-Shin', 'Chang, Hun-Soo', 'Son, Ji-Hye', 'Baek, Dong-Gyu', 'Lee, Jun-Suk', 'Park, Choon-Sik']",Allergy Asthma Immunol Res,,,True
3f8693d47aa1365387a666ecb41f5ced3ee2fc3e,PMC,"Safety studies conducted on pecan shell fiber, a food ingredient produced from ground pecan shells",http://dx.doi.org/10.1016/j.toxrep.2015.11.011,PMC5615425,28959526,CC BY-NC-ND,"Use of pecan shell fiber in human food is presently limited, but could increase pending demonstration of safety. In a 91-day rat study, pecan shell fiber was administered at dietary concentrations of 0 (control), 50 000, 100 000 or 150 000 ppm. There was no effect of the ingredient on body weight of males or females or food consumption of females. Statistically significant increases in food consumption were observed throughout the study in 100 000 and 150 000 ppm males, resulting in intermittent decreases in food efficiency (150 000 ppm males only) that were not biologically relevant. All animals survived and no adverse clinical signs or functional changes were attributable to the test material. There were no toxicologically relevant changes in hematology, clinical chemistry or urinalysis parameters or organ weights in rats ingesting pecan shell fiber. Any macroscopic or microscopic findings were incidental, of normal variation and/or of minimal magnitude for test substance association. Pecan shell fiber was non-mutagenic in a bacterial reverse mutation test and non-clastogenic in a mouse peripheral blood micronucleus test. Based on these results, pecan shell fiber has an oral subchronic (13-week) no observable adverse effect level (NOAEL) of 150 000 ppm in rats and is not genotoxic at the doses analyzed.",2015 Dec 10,"['Dolan, Laurie', 'Matulka, Ray', 'Worn, Jeffrey', 'Nizio, John']",Toxicol Rep,,,False
e14d8123b56a1b4825bf8aa262ff4f4d0f9549b4,PMC,The Relationship between Airway Inflammation and Exacerbation in Chronic Obstructive Pulmonary Disease,http://dx.doi.org/10.4046/trd.2017.0085,PMC5617848,28905537,CC BY-NC,"Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammatory response and airflow limitation. Acute exacerbation involves increased inflammatory burden leading to worsening respiratory symptoms, including dyspnea and sputum production. Some COPD patients have frequent exacerbations (two or more exacerbations per year). A substantial proportion of COPD patients may remain stable without exacerbation. Bacterial and viral infections are the most common causative factors that breach airway stability and lead to exacerbation. The increasing prevalence of exacerbation is associated with deteriorating lung function, hospitalization, and risk of death. In this review, we summarize the mechanisms of airway inflammation in COPD and discuss how bacterial or viral infection, temperature, air pollution, eosinophilic inflammation, and concomitant chronic diseases increase airway inflammation and the risk of exacerbation.",2017 Oct 4,"['Perng, Diahn-Warng', 'Chen, Pei-Ku']",Tuberc Respir Dis (Seoul),,,True
60522266645f5d89d709c2a6dc0f45a072f64dfd,PMC,Elucidation of Bacterial Pneumonia-Causing Pathogens in Patients with Respiratory Viral Infection,http://dx.doi.org/10.4046/trd.2017.0044,PMC5617852,28905531,CC BY-NC,"BACKGROUND: Bacterial pneumonia occurring after respiratory viral infection is common. However, the predominant bacterial species causing pneumonia secondary to respiratory viral infections other than influenza remain unknown. The purpose of this study was to know whether the pathogens causing post-viral bacterial pneumonia vary according to the type of respiratory virus. METHODS: Study subjects were 5,298 patients, who underwent multiplex real-time polymerase chain reaction for simultaneous detection of respiratory viruses, among who visited the emergency department or outpatient clinic with respiratory symptoms at Ulsan University Hospital between April 2013 and March 2016. The patients' medical records were retrospectively reviewed. RESULTS: A total of 251 clinically significant bacteria were identified in 233 patients with post-viral bacterial pneumonia. Mycoplasma pneumoniae was the most frequent bacterium in patients aged <16 years, regardless of the preceding virus type (p=0.630). In patients aged ≥16 years, the isolated bacteria varied according to the preceding virus type. The major results were as follows (p<0.001): pneumonia in patients with influenza virus (type A/B), rhinovirus, and human metapneumovirus infections was caused by similar bacteria, and the findings indicated that Staphylococcus aureus pneumonia was very common in these patients. In contrast, coronavirus, parainfluenza virus, and respiratory syncytial virus infections were associated with pneumonia caused by gram-negative bacteria. CONCLUSION: The pathogens causing post-viral bacterial pneumonia vary according to the type of preceding respiratory virus. This information could help in selecting empirical antibiotics in patients with post-viral pneumonia.",2017 Oct 1,"['Jung, Hwa Sik', 'Kang, Byung Ju', 'Ra, Seung Won', 'Seo, Kwang Won', 'Jegal, Yangjin', 'Jun, Jae-Bum', 'Jung, Jiwon', 'Jeong, Joseph', 'Jeon, Hee-Jeong', 'Ahn, Jae-Sung', 'Lee, Taehoon', 'Ahn, Jong Joon']",Tuberc Respir Dis (Seoul),,,True
018b5b5f732e955d349e14a83481739502ae104c,PMC,"Potential risk of viral transmission from flying foxes to domestic animals and humans on the southern coast of West Java, Indonesia",http://dx.doi.org/10.1292/jvms.17-0222,PMC5627338,28724851,CC BY-NC-ND,"Flying foxes have been considered to be involved in the transmission of serious infectious diseases to humans. Using questionnaires, we aimed to determine the direct and/or indirect contacts of flying foxes in an Indonesian nature conservation area with domestic animals and humans living in the surrounding area. We surveyed 150 residents of 10 villages in West Java. Villages were classified into 3 groups: inside and/or within 1 km from the outer border of the conservation area and 1–5 km or 5–10 km away from the reserve’s outer border. Data were collected by direct interview using a structured questionnaire consisting of the respondent characteristics (age, sex and occupation); histories of contacts between flying foxes and humans, dogs and other domestic animals; and knowledge about infectious diseases, mainly rabies, in flying foxes. We found that flying foxes from the nature conservation area often enter residential areas at night to look for food, especially during the fruit season. In these residential areas, flying foxes had direct contacts with humans and a few contacts with domestic animals, especially dogs. People who encounter flying foxes seldom used personal protective equipment, such as leather gloves, goggles and caps. The residents living around the conservation area mostly had poor knowledge about flying foxes and disease transmission. This situation shows that the population in this region is at a quite high risk for contracting infectious diseases from flying foxes.",2017 Sep 20,"['BASRI, Chaerul', 'ARIFIN, Eko Muhammad Zainal', 'TAKEMAE, Hitoshi', 'HENGJAN, Yupadee', 'IIDA, Keisuke', 'SUDARNIKA, Etih', 'ZAHID, Abdul', 'SOEJOEDONO, Retno Damayanti', 'SUSETYA, Heru', 'SUMIARTO, Bambang', 'KOBAYASHI, Ryosuke', 'AGUNGPRIYONO, Srihadi', 'HONDO, Eiichi']",J Vet Med Sci,,,True
db20f62a0cf1a00fc1860d2ce41c2d60ac7ae49a,PMC,Identification of co-infection by rotavirus and parvovirus in dogs with gastroenteritis in Mexico,http://dx.doi.org/10.1016/j.bjm.2017.03.008,PMC5628314,28716388,CC BY-NC-ND,"This is the first report on circulating canine rotavirus in Mexico. Fifty samples from dogs with gastroenteritis were analyzed used polymerase chain reaction and reverse transcription polymerase chain reaction in order to identify parvovirus and rotavirus, respectively; 7% of dogs were infected with rotavirus exclusively, while 14% were co-infected with both rotavirus and parvovirus; clinical signs in co-infected dogs were more severe.",2017 Jun 24,"['Ortega, Ariadna Flores', 'Martínez-Castañeda, José Simón', 'Bautista-Gómez, Linda G.', 'Muñoz, Raúl Fajardo', 'Hernández, Israel Quijano']",Braz J Microbiol,,,False
c608d6c2fbf042864e6c93a4f8dbd52f80aeb2c0,PMC,Human Rhinovirus Detection by PCR in Febrile Infants and Risk of Concomitant Bacterial Infection,http://dx.doi.org/10.1093/ofid/ofx163.1865,PMC5630716,,CC BY-NC-ND,"BACKGROUND: Studies have shown that well-appearing febrile infants (FI) with viral respiratory infections have a reduced risk of bacterial infections (BI; urinary tract infection, bloodstream infection, meningitis). Respiratory testing by PCR allows detection of human rhinovirus (HRV), but few data exist on the risk of concomitant BI in HRV-positive FI. METHODS: We identified well-appearing FI 1–90 days old within Intermountain Healthcare evaluated in the ED or inpatient setting (IP) with viral respiratory testing by PCR (RVPCR) from August 2007 to August 2016. Respiratory viruses detected by RVPCR included: adenovirus, coronavirus, human metapneumovirus, influenza A/B, parainfluenza 1–4, RSV and HRV. We used relative risk (RR) to compare the risk of BI for infants with HRV vs. non-HRV viruses detected. Similarly, we used RR to compare risk of UTI and invasive bacterial infection (IBI; bacteremia and meningitis) for infants with HRV detected compared with those who were virus negative. RESULTS: 10,964 FI were evaluated in the ED/IP during the study period. 4037 (37%) had RVPCR and were included. 2212 (55%) FI were positive for a respiratory virus and 73% were 29–90 days old. HRV was detected alone in 1392 (34%) and non-HRV viruses were detected in 820 (20%). The overall frequency of BI in the cohort was 9.5%. FI with HRV were more likely to have BI when compared with those with non-HRV viruses [7.8% vs 3.7% P < 0.0001; RR 2.12 (95% CI; 1.43–3.15)]. When compared with virus-negative infants, HRV detection in infants 1–28 days did not decrease the risk for UTI [RR 0.87 (95% CI 0.58–1.29)]; risk of IBI was statistically decreased [RR 0.41 (95% CI 0.19–0.88)] but with wide CI approaching 1 suggesting that this may not be clinically meaningful. Similarly, UTI risk in infants 29–90 days was statistically lower with HRV detection [RR 0.78 (95% CI 0.65–0.95)], but unlikely to be clinically important. For infants 29–90 days with HRV, risk of IBI was statistically decreased [RR 0.52 (95% CI 0.34–0.80)] with possible clinical relevance. CONCLUSION: HRV detection was common in young febrile infants. Infants with HRV were at higher risk of BI than infants with non-HRV infection. Detection of HRV did not meaningfully change risk for UTI at any age or meaningfully impact risk of IBI in infants 1–28 days. HRV detection may be associated with a decreased risk for IBI in infants 29–90 days. DISCLOSURES: A. J. Blaschke, BioFire Diagnostics LLC: Collaborator, Have intellectual property in BioFire Diagnostics through the University of Utah and Investigator, Licensing agreement or royalty and Research support; J. Daly, Biofire: Grant Investigator, Grant recipient; C. L. Byington, BioFire: Collaborator and Grant Investigator, Licensing agreement or royalty and Research grant",2017 Oct 4,"['Blaschke, Anne J', 'Korgenski, E Kent', 'Wilkes, Jacob', 'Presson, Angela', 'Thorell, Emily', 'Stockmann, Chris', 'Knackstedt, Elizabeth', 'Reynolds, Carolyn', 'Schunk, Jeff', 'Daly, Judy', 'Byington, Carrie L']",Open Forum Infect Dis,,,False
7a23e2c3d89a29b68ac86d5d0b6548df272d6e6e,PMC,Painting the Gown Red: Using a Colored Paint Quality Improvement Process to Evaluate Healthcare Worker Personal Protective Equipment for Highly Pathogenic Infections,http://dx.doi.org/10.1093/ofid/ofx163.1031,PMC5630798,,CC BY-NC-ND,"BACKGROUND: Personal protective equipment (PPE) and strict infection control techniques are the primary methods by which healthcare workers (HCW) can avoid exposure during the treatment of patients with highly pathogenic infections such as Ebola Virus Disease (EVD) or the Middle East Respiratory Syndrome coronavirus (MERS-CoV). There is currently no consensus for the types of PPE that are recommended to be worn by HCWs, nor is there a universal process for the donning and doffing of PPE. METHODS: HCWs from Bellevue Hospital participate in quarterly PPE trainings as part of the Special Pathogens Program (SPP), which consist of didactic sessions as well as an evaluation of donning and doffing techniques. A total of 50 HCWs completed the training curriculum in 2017. During the doffing process, PPE trainers applied corn start powder paint (Chameleon Colors; American Fork, UT) to the participants’ gloved hands between multiple steps of PPE removal. At the end of the process, the areas where paint was found on was documented including the outer surgical gown, the powered air purifying respirator (PAPR) helmet and shroud, the inner impermeable suit, the knee-high boots and boot covers, and the extended-cuff gloves. RESULTS: The areas of PPE that were most marked with paint were the lower shoulders and upper arms of the surgical gowns, the top sides of the PAPR shroud, the front upper chest area, and the center back of the inner impermeable suits. In a majority of cases no powder paint was noted on the knee-high boots. In a minority of cases, paint was observed on the inside upper chest area of the surgical gown. These paint markings were used to discuss potential breaches in PPE doffing technique in real-time, as well as identify areas to target in future PPE trainings. CONCLUSION: The powdered paint quality improvement process for donning and doffing PPE is a method to evaluate the complex PPE dressing procedure. It is particularly useful given the fact that it is incumbent on each hospital or healthcare system to develop its own processes and procedures for PPE, as well as maintain readiness through periodic trainings. Powdered paint can identify vulnerabilities in their process as well as areas that require further education. DISCLOSURES: All authors: No reported disclosures.",2017 Oct 4,"['Eiras, Daniel', 'Echeverri, Andrea', 'Toale, Kieran', 'Tennill, Patricia', 'Evans, Laura']",Open Forum Infect Dis,,,False
0ae3fdef0f50723b9cab821aeeb8bf9c41daec50,PMC,"Broad-spectrum Investigational Agent GS-5734 for the Treatment of Ebola, MERS Coronavirus and Other Pathogenic Viral Infections with High Outbreak Potential",http://dx.doi.org/10.1093/ofid/ofx180.008,PMC5630887,,CC BY-NC-ND,"BACKGROUND: Recent viral outbreaks with significant mortality such as Ebola virus (EBOV), SARS-coronavirus (CoV), and MERS-CoV reinforced the need for effective antiviral therapeutics to control future epidemics. GS-5734 is a novel nucleotide analog prodrug in the development for treatment of EBOV. METHOD: Antiviral activity of GS-5734 has been established in vitro against a wide range of pathogenic RNA virus families, including filoviruses, coronaviruses, and paramyxoviruses (EC(50) = 37 to 200 nM) (Warren et al., Nature 2016; Sheahan et al., Sci Transl Med 2017; Lo et al., Sci Rep 2017). Herein, we describe the in vivo translation of the broad-spectrum activity of GS-5734 in relevant animal disease models for Ebola, Marburg, MERS-CoV, and Nipah. RESULT: Therapeutic efficacy against multiple filoviruses with 80–100% survival was observed in rhesus monkeys infected with lethal doses of EBOV (Kikwit/1995 or Makona/2014) or Marburg virus and treated with once daily intravenous (IV) administration of 5 to 10 mg/kg GS-5734 beginning 3 to 5 days post-infection (p.i.). In all rhesus monkey filovirus infection models, GS-5734 significantly reduced systemic viremia and ameliorated severe clinical disease signs and anatomic pathology. In mice infected with MERS-CoV, twice daily subcutaneous administration of 25 mg/kg GS-5734 beginning 1 day p.i. significantly reduced lung viral load and improved respiratory function. In rhesus monkeys, once-daily IV administration of 5 mg/kg GS-5734 initiated 1 day prior to MERS-CoV infection reduced lung viral load, improved clinical disease signs, and ameliorated severe lung pathology. Finally, in African green monkeys infected with a lethal dose of Nipah virus therapeutic once-daily IV administration of 10 mg/kg GS-5734, starting 1 day p.i. resulted in 100% survival to at least day 35 without any major respiratory or CNS symptoms. CONCLUSION: GS-5734 is currently being tested in a phase 2 study in male Ebola survivors with persistent viral RNA in semen. Lyophilized drug formulation has been developed that can be administered to humans via a 30-minutes IV infusion and does not require cold chain storage. Together, these results support further development of GS-5734 as a broad-spectrum antiviral to treat viral infections with high mortality and significant outbreak potential. DISCLOSURES: R. Jordan, Gilead: Employee, Salary. J. Feng, Gilead: Employee, Salary I. Trantcheva, Gilead: Employee, Salary. D. Babusis, Gilead: Employee, Salary. D. Porter-Poulin, Gilead: Employee, Salary. R. Bannister, Gilead: Employee, Salary R. Mackman, Gilead: Employee, Salary. D. Siegel, Gilead: Employee, Salary A. Ray, Gilead: Employee, Salary, T. Cihlar, Gilead: Employee, Salary.",2017 Oct 4,"['Jordan, Robert', 'Hogg, Alison', 'Warren, Travis', 'De Wit, Emmie', 'Sheahan, Timothy', 'Lo, Michael', 'Soloveva, Veronica', 'Weidner, Jessica', 'Gomba, Laura', 'Feldmann, Friederike', 'Cronin, Jacqueline', 'Sims, Amy', 'Cockrell, Adam', 'Feng, Joy', 'Trantcheva, Iva', 'Babusis, Darius', 'Porter-Poulin, Danielle', 'Bannister, Roy', 'Mackman, Richard', 'Siegel, Dustin', 'Ray, Adrian', 'Denison, Mark', 'Spiropoulou, Christina', 'Nichol, Stuart', 'Cihlar, Tomas', 'Baric, Ralph', 'Feldmann, Heinrich', 'Bavari, Sina']",Open Forum Infect Dis,,,False
566426c066595e316481096929ea8f42a76b1a4b,PMC,Effect of Rapid Molecular Diagnostic Testing and Antimicrobial Stewardship on Antimicrobial Therapy of Respiratory Infections,http://dx.doi.org/10.1093/ofid/ofx163.1668,PMC5631006,,CC BY-NC-ND,"BACKGROUND: Rapid molecular methods have created new opportunities for the clinical microbiology laboratory to affect patient care in the areas of initial diagnosis and therapy. Rapid diagnostic tests provide collaborative opportunities for antimicrobial stewardship Teams (AST) to improve patient outcomes and decrease antimicrobial use. In January of 2017 our institution initiated use of a FDA approved multiplex polymerase chain reaction (PCR) Respiratory Panel. The objective of this evaluation was to assess the clinical impact along with procalcitonin (PCT) on quality of patient care when used in conjunction with antimicrobial stewardship. METHODS: Molecular testing was performed using the BioFire FilmArray® Respiratory Panel [RP] (BioMerieux). The medical staff was encouraged to order an Influenza/RSV PCR test prior to ordering the full RP. The results of RP and PCT were available the same day as ordered. AST recommended the RP as part of its intervention on several patients and provided advice based on results. RESULTS: From January-April the results of 81 tests for the respiratory panel were evaluated. Of these 30 were positive (+) for virus (most common-Human Metapneumovirus [HMV]-13, Coronavirus-7). PCT (ng/mL) results were available on 69. Most common final diagnosis: Pneumonia-31; AECOPD-16. Effect on duration of antimicrobial therapy (ABX) and hospital length of stay (LOS): CONCLUSION: The results of the RP led to a decrease in ABX duration, which was most profound in the patients for whom AST intervened. LOS was also reduced. Utilization of RP and PCT facilitated better ABX use. DISCLOSURES: T. M. File Jr., BioMerieux: Scientific Advisor, Consulting fee",2017 Oct 4,"['File, Thomas M', 'Politis, Paula', 'Tan, Michael J', 'Kallstrom, George']",Open Forum Infect Dis,,,False
568b4324519f51485f598d1819341d084dee43a8,PMC,Asthma Exacerbations and Risk of Emergency Department Management Failure: Burden and Impact of Various Respiratory Pathogens in a Pediatric Population,http://dx.doi.org/10.1093/ofid/ofx163.1864,PMC5631216,,CC BY-NC-ND,"BACKGROUND: In asthmatic children, 60–80% of exacerbations are triggered by respiratory pathogens and represent an important burden of illness. The impact of pathogens on exacerbation severity and treatment response remains unclear. Our aim was to describe the prevalence of respiratory pathogens in children presenting to the emergency department (ED) and investigate the association between pathogens and (i) exacerbation severity on presentation and (ii) ED treatment failure. METHODS: We performed a secondary analysis of the DOORWAY study, a prospective multi-center cohort of children (1–17 years) presenting to the ED with moderate or severe asthma exacerbation. All received per protocol oral corticosteroids and bronchodilators. Nasopharyngeal (NPA) secretions were analyzed by RT-PCR for 30 different pathogens. Linear and logistic multivariate regression models were used to estimate absolute risks and risk differences (RD) with their 95% CI representing average marginal effects. RESULTS: Of 958 patients with NPA specimens, 591 (61.7%) were positive for ≥ 1 pathogens; human rhinovirus (HRV) was the most prevalent (29.4%). Non-HRV infection (RD -12.9%; 95% CI -19.5; -6.3), human metapneumovirus (RD -13.6%; 95% CI -23.0%; -4.3%) and parainfluenza virus (PIV) (RD -31.7%; 95% CI -44.5%; -18.9%) were negatively associated with severity; no association was found between severity and the presence of any pathogen, co-infection, or the specific viruses HRV-A, HRV-B, HRV-C, respiratory syncytial virus, influenza (INF), enterovirus serotype D68, adenovirus or coronavirus. The risk of treatment failure in the absence of a pathogen was 12.5% (95% CI 9.0%; 16.0%). The presence of any pathogen (RD 8.2%; 95% CI 3.3%; 13.1%) and non-HRV infection as a group (RD 13.1%; 95% CI 6.4%; 19.8%), and of INF and PIV specifically (RD 24.9%; 95% CI 4.7%; 45.1% and RD 34.1%; 95% CI 7.5%; 60.7%) were positively associated with treatment failure. CONCLUSION: In this large cohort of children with moderate or severe exacerbation, no single respiratory pathogen was associated with higher severity on presentation. However, in addition to any pathogen and non-HVR infection, INF and PIV were specifically associated with higher treatment failure in the ED, supporting the need for influenza prevention, pathogen identification at presentation and exploration of pathogen-therapy interaction. DISCLOSURES: All authors: No reported disclosures.",2017 Oct 4,"['Merckx, Joanna', 'Ducharme, Francine M', 'Quach, Caroline']",Open Forum Infect Dis,,,False
c8fac36a0f97b307c5a12f0aa4bf167e2285fc6e,PMC,The Utility of Preliminary Patient Evaluation in a Febrile Respiratory Infectious Disease Unit Outside the Emergency Department,http://dx.doi.org/10.1093/ofid/ofx163.349,PMC5631788,,CC BY-NC-ND,"BACKGROUND: Acute respiratory illnesses are the leading cause of death from infectious diseases around the world, and occasional outbreaks of particularly virulent strains are can be public health disasters. Recently, a large outbreak of fatal Middle East respiratory syndrome-coronavirus (MERS-CoV) occurred following a single patient exposure in the emergency department (ED) of the Samsung Medical Center, a tertiary-care hospital in South Korea, which resulted in significant public health and economic burden. After this outbreak, a febrile respiratory infectious disease unit (FRIDU) with a negative pressure ventilation system was constructed outside the emergency department (ED) in 2015, to screen for patients with contagious diseases requiring isolation. METHODS: This is a retrospective cohort study of patients who visited the ED with febrile illness between August 2015 and July 2016. Ultimately, 1562 patients who were hospitalized after FRIDU screening were analyzed. The level of isolation recommended during their screening at the FRIDU was compared with the level deemed appropriate given their final diagnosis. RESULTS: Of the 1562 patients screened at the FRIDU, 198 (13%) were isolated, 194 (12%) were reverse isolated, and 1170 (75%) were not isolated. While hospitalized, 97 patients (6%) were confirmed to have a contagious disease requiring isolation, such as tuberculosis; 207 patients (13%) were confirmed to be immunocompromised and to require reverse isolation, mainly due to neutropenia; and the remaining 1258 patients (81%) did not require isolation. The correlation coefficient for isolation consistency was 0.565 (P < 0.001). No serious nosocomial outbreaks of contagious diseases occurred. During FRIDU screening, 114 patients were admitted to the resuscitation zone due to clinical instability, and three of these patients died. CONCLUSION: The initial isolation levels resulting from FRIDU screening were moderately well correlated with the isolation levels required by the final diagnosis, demonstrating the utility of pre-hospitalization screening units. However, the risks of deterioration during the screening process remain challenges. DISCLOSURES: All authors: No reported disclosures.",2017 Oct 4,"['Sik Kang, Jun', 'Yoon, Hee', 'Jhun, Byung Woo', 'Lim, Seong Mi', 'Ko, Eun Sil', 'Park, Joo Hyun', 'Hwang, Sung Yeon', 'Lee, Se Uk', 'Lee, Tae Rim', 'Cha, Won Chul', 'Shin, Tae Gun', 'Sim, Min Seob', 'Jo, Ik Joon']",Open Forum Infect Dis,,,False
b1e33dadba2e2cd6e561811e3f201a29d9ae81d4,PMC,Study to Address Threats of Acute Respiratory Infections among Congregate Military Populations (ATARI),http://dx.doi.org/10.1093/ofid/ofx163.724,PMC5631925,,CC BY-NC-ND,"BACKGROUND: More than 90% of active duty personnel receive influenza vaccinations yearly. Despite high coverage, influenza-like illnesses (ILI) remain a frequent cause of missed duty and hospitalizations, particularly in U.S. military recruits. More research is needed on the epidemiology and etiology of ILI to reduce the burden of respiratory infections in congregated military settings. METHODS: We conducted a prospective cohort study to assess ILI patterns among US Army recruits in a 9-week basic combat training course at Ft. Benning, GA. Demographic data, vaccination history, and information on recent illness were collected at enrollment in January 2017. Participants were divided into two platoons with staggered biweekly visit schedules. Visits occurred from reception through training, with nasal swabs and symptom surveys (all visits) and blood draws (weeks 8 and 9). Nasal specimens were used to detect clinical and colonizing pathogens using the Diatherix TEM-PCR Respiratory Panel. RESULTS: A total of 90 recruits were enrolled in the study. Twelve recruits were lost due to training attrition in the first week of the study. The participants were male and the mean age was 23 yo (SD 4.9). There were 10 (13%) cases of ILI reported among the 78 remaining participants, 6 in week 1, 3 in week 2 and 1 in week 9. The most frequently detected pathogens in the 10 symptomatic cases were coronavirus (5, 50%), rhinovirus (4, 40%), other enterovirus (3, 30%), and influenza A (2, 20%). Pathogen co-detections were common, 8 out 10 cases were associated with 2 pathogens, representing 7 unique combinations. While rhinovirus and coronavirus were most common among asymptomatic trainees, 10% had detectable influenza A. Detection of multiple pathogens was common in the first two weeks of training (50% among those who had viral detection). The study is still in progress. CONCLUSION: Symptomatic ILI was associated with coronavirus, rhinovirus, and enterovirus, in addition to influenza in the early weeks of training. Coronavirus and rhinovirus also circulated widely among healthy recruits, along with influenza. The findings will inform ILI control strategies for congregated military trainees. DISCLOSURES: E. Grigorenko, Diatherix Laboratories: Employee, Salary.L. Malone, Diatherix Laboratories: Employee, Salary.",2017 Oct 4,"['Coles, Christian', 'Chen, Wei-Ju', 'Milzman, Jacqueline Owens', 'Grigorenko, Elena', 'Robinson, Scott', 'Jones, Carol', 'Moreno, Nicole', 'Burgess, Timothy', 'Malone, Leslie']",Open Forum Infect Dis,,,False
fdb7d85b1192873737a2027af1096fbc742c61f1,PMC,"Human Coronavirus (HCoV) Infection Among Adults in Cleveland, Ohio: An Increasingly Recognized Respiratory Pathogen",http://dx.doi.org/10.1093/ofid/ofx163.729,PMC5631947,,CC BY-NC-ND,"BACKGROUND: Human Coronaviruses (CoV) have been long recognized as a common cause of respiratory tract disease including severe respiratory tract illness, yet there are few recent studies characterizing disease among adults in the United States. Here, we describe CoV infections and clinical characteristics among adults (>18 years) presenting with respiratory illness in Cleveland, Ohio. METHODS: Between February 1, 2016 and April 30, 2017, 2949 nasopharyngeal swab specimens were analyzed by NxTAG Respiratory Pathogen Panel in adults presenting with respiratory illness at MetroHealth Medical Center. Clinical data were collected on adults whose samples screened positive for CoV-HKU1, CoV-OC43, CoV-229E or CoV-NL63. RESULTS: Coronaviruses were detected in 192 (6.5%) adults including 105 (3.5%) OC43, 67 (2.3%) 229E, 13 (0.4%) HKU1 and 7 (0.2%) NL63. The majority of adults with coronavirus infection were females (66.2%) with a median age of 53 years. Common comorbidities included smoking (40.0%), asthma (38.0%), COPD (35.4%), and inhaled corticosteroid use (28.6%). Eighty-five (46.4%) required admission to the hospital. Common presenting symptoms included shortness of breath (42.7%) and cough (31.0%) whereas fever was uncommon (12.5%). Gastrointestinal symptoms were more common in HKU1 and NL63 infected adults. Seventy-three percent of coronavirus disease occurred between the months of January and March. Despite the recognition of coronavirus infection, 70 (36.5%) received antibiotics for their disease. CONCLUSION: This study provides needed insight into clinical characteristics and severity associated with coronavirus infection in adults. Coronavirus infection should be considered in differential diagnosis of respiratory tract illness in adults including those that require hospitalization, have a history of smoking and have pulmonary comorbidities. DISCLOSURES: All authors: No reported disclosures.",2017 Oct 4,"['Kanwar, Anubhav', 'Selvaraju, Suresh', 'Esper, Frank']",Open Forum Infect Dis,,,False
c8ce59ad64e4d4ddaa03ca89ade60d4086a60fba,PMC,"Human Coronavirus Circulation in the USA, 2014‒2017",http://dx.doi.org/10.1093/ofid/ofx163.727,PMC5632013,,CC BY-NC-ND,"BACKGROUND: Human coronaviruses (HCoV) OC43, 229E, NL63 and HKU1 commonly cause upper respiratory tract infections, but can also cause severe lower respiratory tract disease. Increased use of diagnostic assays for respiratory viruses has facilitated detection and, since 2014, voluntary reporting of HCoV to the National Respiratory and Enteric Virus Surveillance System (NREVSS). METHODS: We reviewed weekly aggregate test results for HCoV OC43, 229E, NL63 and HKU1 voluntarily reported to NREVSS by U.S. hospital and clinical laboratories from July 1, 2014‒April 30, 2017. Laboratories reporting any HCoV result using PCR were included, and the weekly percentage of positive HCoV tests by type was calculated. For a subset of HCoV detections reported to NREVSS via the Public Health laboratory Interoperability Project (PHLIP), which collects individual-level demographic data, we described age distribution and sex. Age distribution by HCoV type was compared using the Kruskal–Wallis test. RESULTS: 154 laboratories, across all 9 U.S. census divisions, reported 834,742 tests for HCoV; 18,514 (2.2%) were positive for HCoV-OC43, 8,363 (1.0%) for HCoV-NL63, 6,828 (0.8%) for HCoV-229E, and 5,170 (0.6%) for HCoV-HKU1. The percentage of tests positive for HCoV generally peaked between December and March (Figure 1). HCoV-OC43 showed distinct annual peaks with variation in magnitude by year. HCoV-HKU1 and NL63 had similar patterns, each with notable peaks during winter 2016 compared with 2015 or 2017. HCoV-229E showed a discernable peak in 2017 compared with the previous 2 years. Of 20,533 individuals with HCoV test results reported via PHLIP, 1,589 (7.7%) tested positive for any HCoV; 50% of HCoV-positive individuals were male, and the median age was 22 (range 0–96) years. Age distribution differed between HCoV types (P < 0.01, Figure 2). CONCLUSION: Over approximately 3 seasons, peak positivity for HCoV occurred during winter months, and annual differences in circulation by HCoV type were observed. Continued testing and surveillance for HCoV will allow for further characterization of circulation trends over time and by geographic region, and improved understanding of the contribution of HCoV to the winter respiratory virus season. DISCLOSURES: All authors: No reported disclosures.",2017 Oct 4,"['Biggs, Holly M', 'Killerby, Marie E', 'Haynes, Amber K', 'Dahl, Rebecca M', 'Gerber, Susan I', 'Watson, John T']",Open Forum Infect Dis,,,False
092880cc76f470dd9cca8233d83c884c0c5edf94,PMC,Fibroblasts: The Unknown Sentinels Eliciting Immune Responses Against Microorganisms,http://dx.doi.org/10.1556/1886.2017.00009,PMC5632742,29034104,CC BY-NC,"Fibroblasts are present in all tissues but predominantly in connective tissues. Some of their functions include contractility, locomotion, collagen and elastin fiber production, and the regulation and degradation of the extracellular matrix. Also, fibroblasts act as sentinels to produce inflammatory mediators in response to several microorganisms. There is evidence that fibroblasts can synthesize toll-like receptors (TLRs), antimicrobial peptides, proinflammatory cytokines, chemokines, and growth factors, which are important molecules involved in innate immune response against microorganisms. Fibroblasts can express TLRs (TLR-1 to TLR-10) to sense microbial components or microorganisms. They can synthesize antimicrobial peptides, such as LL-37, defensins hBD-1, and hBD-2, molecules that perform antimicrobial activity. Also, they can produce proinflammatory cytokines, such as TNFα, INFγ, IL-6, IL-12p70, and IL-10; other chemokines, such as CCL1, CCL2, CCL5, CXCL1, CXCL8, CXCL10, and CX3CL1; and the growth factors granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) to induce and recruit inflammatory cells. According to their immunological attributes, we can conclude that fibroblasts are sentinel cells that recognize pathogens, induce the recruitment of inflammatory cells via cytokines and growth factors, and release antimicrobial peptides, complying with the characteristics of real sentinels.",2017 Aug 19,"['Bautista-Hernández, Luis Antonio', 'Gómez-Olivares, José Luis', 'Buentello-Volante, Beatriz', 'Bautista-de Lucio, Victor Manuel']",Eur J Microbiol Immunol (Bp),,,True
b51603b65f40d384c4aa0f11379f0dcc387e46b1,PMC,Use of Obstetric Practice Web Sites to Distribute Zika Virus Information to Pregnant Women During a Zika Virus Outbreak,http://dx.doi.org/10.1097/PHH.0000000000000537,PMC5636051,28125540,CC BY-NC-ND,"OBJECTIVE: To describe the current use of obstetric practice Web sites to disseminate Zika virus information to patients. DESIGN: Review of 913 randomly selected practice Web sites and associated social media accounts in January and August 2016. SETTING: Obstetric practice Web sites and associated social media accounts, United States of America. PARTICIPANTS: N/A. MAIN OUTCOME MEASURES: Proportion of obstetric practice Web sites and linked social media accounts providing Zika virus information. RESULTS: Twenty-five percent and 35% of obstetric practice Web sites had information posted about Zika virus in January 2016 and August 2016, respectively. Between the 2 time points, the proportion of practices posting Zika virus content on Facebook and Twitter declined (Facebook: 15% in January, 9% in August; Twitter: 12% in January, 8% in August). In August, the most frequently observed Zika virus–related content themes were the use of insect repellent (14%) and travel advisories (14%). At both time points, practices affiliated with large university hospitals were more likely to have posted information on Zika virus than independent OB/GYN-only practices: January: odds ratio (OR) (95% confidence interval [CI]) = 5.68 (3.50-9.20); August: OR (95% CI) = 8.37 (5.31-13.17). Similarly, practices associated with nonuniversity hospitals were more likely to have posted information than independent OB/GYN-only practices: January: OR (95% CI) = 2.71 (1.88-3.92); August: OR (95% CI) = 6.75 (4.75-9.60). CONCLUSION: Obstetric care practices are not fully utilizing their practice Web sites to relay Zika virus information to their patients. Since practitioner-sponsored Web sites have the capacity to directly reach the populations at greatest risk for Zika virus complications, public health professionals should consider adapting their materials and provider outreach campaigns to more easily accommodate Web site–based information dissemination during this type of public health emergency. There must be greater recognition of the value information gains in the eyes of the patient when it is validated by their own provider, especially when that patient is part of the highest-risk population for a given emergency. Public health organizations should strive to minimize the burden it takes for providers to relay useful resources to patients in order to maximize the impact that those resources can have.",2017 Nov 29,"['Lehnert, Jonathan D.', 'Ellingson, Mallory K.', 'Goryoka, Grace W.', 'Kasturi, Raghuraj', 'Maier, Emily', 'Chamberlain, Allison T.']",J Public Health Manag Pract,,,True
f5de8066a6e6df907e2389816f2372a427235a9f,PMC,Comparison of cytokine expression profiles in infants with a rhinovirus induced lower respiratory tract infection with or without wheezing: a comparison with respiratory syncytial virus,http://dx.doi.org/10.3345/kjp.2017.60.9.296,PMC5638836,29042873,CC BY-NC,"PURPOSE: The aim of this study was to evaluate whether infants with rhinovirus (RV) infection-induced wheezing and those with respiratory syncytial virus (RSV) infection-induced wheezing have different cytokine profiles in the acute stage. METHODS: Of the infants with lower respiratory tract infection (LRTI) between September 2011 and May 2012, 88 were confirmed using reverse transcription polymerase chain reaction and hospitalized. Systemic interferon-gamma (IFN-γ), interleukin (IL)-2, IL-12, IL-4, IL-5, IL-13, and Treg-type cytokine (IL-10) responses were examined with multiplex assay using acute phase serum samples. RESULTS: Of the 88 patients, 38 had an RV infection (RV group) and 50 had an RSV infection (RSV group). In the RV group, the IFN-γ and IL-10 concentrations were higher in the patients with than in the patients without wheezing (P=0.022 and P=0.007, respectively). In the RSV group, the differences in IFN-γ and IL-10 concentrations did not reach statistical significance between the patients with and the patients without wheezing (P=0.105 and P=0.965, respectively). The IFN-γ and IL-10 concentrations were not significantly different between the RV group with wheezing and the RSV group with wheezing (P=0.155 and P=0.801, respectively), in contrast to the significant difference between the RV group without wheezing and the RSV group without wheezing (P=0.019 and P=0.035, respectively). CONCLUSION: In comparison with RSV-induced LRTI, RV-induced LRTI combined with wheezing showed similar IFN-γ and IL-10 levels, which may have an important regulatory function.",2017 Sep 21,"['Roh, Da Eun', 'Park, Sook-Hyun', 'Choi, Hee Joung', 'Kim, Yeo Hyang']",Korean J Pediatr,,,True
1cfa24297a36bcd526ad00635440d59bce705a17,PMC,Induction of PrP(Sc)-specific systemic and mucosal immune responses in white-tailed deer with an oral vaccine for chronic wasting disease,http://dx.doi.org/10.1080/19336896.2017.1367083,PMC5639826,28968152,CC BY-NC-ND,"The ongoing epidemic of chronic wasting disease (CWD) within cervid populations indicates the need for novel approaches for disease management. A vaccine that either reduces susceptibility to infection or reduces shedding of prions by infected animals, or a combination of both, could be of benefit for disease control. The development of such a vaccine is challenged by the unique nature of prion diseases and the requirement for formulation and delivery in an oral format for application in wildlife settings. To address the unique nature of prions, our group targets epitopes, termed disease specific epitopes (DSEs), whose exposure for antibody binding depends on disease-associated misfolding of PrP(C) into PrP(Sc). Here, a DSE corresponding to the rigid loop (RL) region, which was immunogenic following parenteral vaccination, was translated into an oral vaccine. This vaccine consists of a replication-incompetent human adenovirus expressing a truncated rabies glycoprotein G recombinant fusion with the RL epitope (hAd5:tgG-RL). Oral immunization of white-tailed deer with hAd5:tgG-RL induced PrP(Sc)-specific systemic and mucosal antibody responses with an encouraging safety profile in terms of no adverse health effects nor prolonged vector shedding. By building upon proven strategies of formulation for wildlife vaccines, these efforts generate a particular PrP(Sc)-specific oral vaccine for CWD as well as providing a versatile platform, in terms of carrier protein and biological vector, for generation of other oral, peptide-based CWD vaccines.",2017 Oct 2,"['Taschuk, Ryan', 'Scruten, Erin', 'Woodbury, Murray', 'Cashman, Neil', 'Potter, Andrew', 'Griebel, Philip', 'Tikoo, Suresh K.', 'Napper, Scott']",Prion,,,True
15b009c611ca19c1c8eac1a7f686e03fe2b4e8ee,PMC,Elevated hepatic DPP4 activity promotes insulin resistance and non-alcoholic fatty liver disease,http://dx.doi.org/10.1016/j.molmet.2017.07.016,PMC5641684,29031724,CC BY-NC-ND,"OBJECTIVE: Increased hepatic expression of dipeptidyl peptidase 4 (DPP4) is associated with non-alcoholic fatty liver disease (NAFLD). Whether this is causative for the development of NAFLD is not yet clarified. Here we investigate the effect of hepatic DPP4 overexpression on the development of liver steatosis in a mouse model of diet-induced obesity. METHODS: Plasma DPP4 activity of subjects with or without NAFLD was analyzed. Wild-type (WT) and liver-specific Dpp4 transgenic mice (Dpp4-Liv-Tg) were fed a high-fat diet and characterized for body weight, body composition, hepatic fat content and insulin sensitivity. In vitro experiments on HepG2 cells and primary mouse hepatocytes were conducted to validate cell autonomous effects of DPP4 on lipid storage and insulin sensitivity. RESULTS: Subjects suffering from insulin resistance and NAFLD show an increased plasma DPP4 activity when compared to healthy controls. Analysis of Dpp4-Liv-Tg mice revealed elevated systemic DPP4 activity and diminished active GLP-1 levels. They furthermore show increased body weight, fat mass, adipose tissue inflammation, hepatic steatosis, liver damage and hypercholesterolemia. These effects were accompanied by increased expression of PPARγ and CD36 as well as severe insulin resistance in the liver. In agreement, treatment of HepG2 cells and primary hepatocytes with physiological concentrations of DPP4 resulted in impaired insulin sensitivity independent of lipid content. CONCLUSIONS: Our results give evidence that elevated expression of DPP4 in the liver promotes NAFLD and insulin resistance. This is linked to reduced levels of active GLP-1, but also to auto- and paracrine effects of DPP4 on hepatic insulin signaling.",2017 Aug 4,"['Baumeier, Christian', 'Schlüter, Luisa', 'Saussenthaler, Sophie', 'Laeger, Thomas', 'Rödiger, Maria', 'Alaze, Stella Amelie', 'Fritsche, Louise', 'Häring, Hans-Ulrich', 'Stefan, Norbert', 'Fritsche, Andreas', 'Schwenk, Robert Wolfgang', 'Schürmann, Annette']",Mol Metab,,,False
eab5c7409c1afb7a1c6357ed9d4fe4b0c3f2fa16,PMC,Detection of respiratory viral and bacterial pathogens causing pediatric community-acquired pneumonia in Beijing using real-time PCR,http://dx.doi.org/10.1016/j.cdtm.2015.06.002,PMC5643733,29062995,CC BY-NC-ND,"OBJECTIVE: The aim of this study was to determine the etiology and prevalence of pediatric CAP in Beijing using a real-time polymerase chain reaction (PCR) technique. METHODS: Between February 15, 2011 and January 18, 2012, 371 pediatric patients with CAP were enrolled at Beijing Children's Hospital. Sixteen respiratory viruses and two bacteria were detected from tracheal aspirate specimens using commercially available multiplex real-time reverse transcription PCR (RT-PCR) kits. RESULTS: A single viral pathogen was detected in 35.3% of enrolled patients, multiple viruses in 11.6%, and virus/bacteria coinfection in 17.8%. In contrast, only 6.5% of patients had a single bacterial pathogen and 2.2% were infected with multiple bacteria. The etiological agent was unknown for 26.7% of patients. The most common viruses were respiratory syncytial virus (RSV) (43.9%), rhinovirus (14.8%), parainfluenza virus (9.4%), and adenovirus (8.6%). In patients under three years of age, RSV (44.6%), rhinovirus (12.8%), and Streptococcus pneumoniae (9.9%) were the most frequent pathogens. In children aged 3–7 years, S. pneumoniae (38.9%), RSV (30.6%), Haemophilus influenzae (19.4%), and adenovirus (19.4%) were most prevalent. Finally in children over seven years, RSV (47.3%), S. pneumoniae (41.9%), and rhinovirus (21.5%) infections were most frequent. CONCLUSIONS: Viral pathogens, specifically RSV, were responsible for the majority of CAP in pediatric patients. However, both S. pneumoniae and H. influenzae contributed as major causes of disease. Commercially available multiplexing real-time PCR allowed for rapid detection of the etiological agent.",2015 Jul 7,"['Zhang, Tie-Gang', 'Li, Ai-Hua', 'Lyu, Min', 'Chen, Meng', 'Huang, Fang', 'Wu, Jiang']",Chronic Dis Transl Med,,,False
c62c030b2ee83baf4f5390cdb28f32f6bce71edf,PMC,A pandemic risk assessment of middle east respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia,http://dx.doi.org/10.1016/j.sjbs.2017.06.001,PMC5643837,29062261,CC BY-NC-ND,"Since the initial emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, a high incidence rate has been observed in Saudi Arabia. This suggests that the country is at continuous risk. The epidemic level of MERS-CoV infection was examined in Saudi Arabia by the Susceptible-Infectious-Recovered (SIR) model using a Bayesian approach for estimation of time dependent reproduction number (R) across a two-year interval (May, 2013-May, 2015) in five defined clusters, followed by sensitivity analysis of the most significant clusters. Significant MERS-CoV peaks were detected in the period between March and May of each year. Moreover, MERS-CoV infection was highlighted in western (40.8%) and central (31.9%) regions, followed by eastern region (20%). The temporal-based Bayesian approach indicated a sub-critical epidemic in all regions in the baseline scenario (R: 0.85–0.97). However, R potential limit was exceeded in the sensitivity analysis scenario in only central and western regions (R: 1.08–1.12) that denoted epidemic level in those regions. The impact of sporadic cases was found relatively insignificant and pinpointed to the lack of zoonotic influence on MERS-CoV transmission dynamics. The results of current study would be helpful for evaluation of future progression of MERS-CoV infections, better understanding and control interventions.",2017 Nov 6,"['Eifan, Saleh A.', 'Nour, Islam', 'Hanif, Atif', 'Zamzam, Abdelrahman M.M.', 'AlJohani, Sameera Mohammed']",Saudi J Biol Sci,,,False
3f95cd9324e4e68dfac149200521e09981091feb,PMC,"Understanding the canine intestinal microbiota and its modification by pro‐, pre‐ and synbiotics – what is the evidence?",http://dx.doi.org/10.1002/vms3.17,PMC5645859,29067182,CC BY-NC,"Interest in the composition of the intestinal microbiota and possibilities of its therapeutic modifications has soared over the last decade and more detailed knowledge specific to the canine microbiota at different mucosal sites including the gut is available. Probiotics, prebiotics or their combination (synbiotics) are a way of modifying the intestinal microbiota and exert effects on the host immune response. Probiotics are proposed to exert their beneficial effects through various pathways, for example production of antimicrobial peptides, enhancing growth of favourable endogenous microorganisms, competition for epithelial colonisation sites and immune‐modulatory functions. Despite widespread use of pro‐, pre‐ and synbiotics, scientific evidence of their beneficial effects in different conditions of the dog is scarce. Specific effects of different strains, their combination or their potential side‐effects have not been evaluated sufficiently. In some instances, in vitro results have been promising, but could not be transferred consistently into in vivo situations. Specific canine gastrointestinal (GI) diseases or conditions where probiotics would be beneficial, their most appropriate dosage and application have not been assessed extensively. This review summarises the current knowledge of the intestinal microbiome composition in the dog and evaluates the evidence for probiotic use in canine GI diseases to date. It wishes to provide veterinarians with evidence‐based information on when and why these products could be useful in preventing or treating canine GI conditions. It also outlines knowledge about safety and approval of commercial probiotic products, and the potential use of faecal microbial transplantation, as they are related to the topic of probiotic usage.",2016 Jan 11,"['Schmitz, Silke', 'Suchodolski, Jan']",Vet Med Sci,,,True
05a12a1fb4a86a4158ad027b911092cfc25bc40b,PMC,Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation,http://dx.doi.org/10.7150/ntno.19796,PMC5646730,29071191,CC BY-NC,"Synthetic nanoparticles play an increasingly significant role in vaccine design and development as many nanoparticle vaccines show improved safety and efficacy over conventional formulations. These nanoformulations are structurally similar to viruses, which are nanoscale pathogenic organisms that have served as a key selective pressure driving the evolution of our immune system. As a result, mechanisms behind the benefits of nanoparticle vaccines can often find analogue to the interaction dynamics between the immune system and viruses. This review covers the advances in vaccine nanotechnology with a perspective on the advantages of virus mimicry towards immune potentiation. It provides an overview to the different types of nanomaterials utilized for nanoparticle vaccine development, including functionalization strategies that bestow nanoparticles with virus-like features. As understanding of human immunity and vaccine mechanisms continue to evolve, recognizing the fundamental semblance between synthetic nanoparticles and viruses may offer an explanation for the superiority of nanoparticle vaccines over conventional vaccines and may spur new design rationales for future vaccine research. These nanoformulations are poised to provide solutions towards pressing and emerging human diseases.",2017 Jun 9,"['Chattopadhyay, Saborni', 'Chen, Jui-Yi', 'Chen, Hui-Wen', 'Hu, Che-Ming Jack']",Nanotheranostics,,,True
5d38ec30f0a4ea9b504808bc6bb2c8793db72e7a,PMC,Recent Advances in Biosensor Development for Foodborne Virus Detection,http://dx.doi.org/10.7150/ntno.20301,PMC5646734,29071193,CC BY-NC,"Outbreaks of foodborne diseases related to fresh produce have been increasing in North America and Europe. Viral foodborne pathogens are poorly understood, suffering from insufficient awareness and surveillance due to the limits on knowledge, availability, and costs of related technologies and devices. Current foodborne viruses are emphasized and newly emerging foodborne viruses are beginning to attract interest. To face current challenges regarding foodborne pathogens, a point-of-care (POC) concept has been introduced to food testing technology and device. POC device development involves technologies such as microfluidics, nanomaterials, biosensors and other advanced techniques. These advanced technologies, together with the challenges in developing foodborne virus detection assays and devices, are described and analysed in this critical review. Advanced technologies provide a path forward for foodborne virus detection, but more research and development will be needed to provide the level of manufacturing capacity required.",2017 Jul 5,"['Neethirajan, Suresh', 'Ahmed, Syed Rahin', 'Chand, Rohit', 'Buozis, John', 'Nagy, Éva']",Nanotheranostics,,,True
854545208a6bc7cafa8744604899e32237ff2047,PMC,Highly pathogenic avian influenza A virus H5N1 non-structural protein 1 is associated with apoptotic activation of the intrinsic mitochondrial pathway,http://dx.doi.org/10.3892/etm.2017.5056,PMC5647739,29067097,CC BY-NC-ND,"Outbreaks of avian influenza A (H5N1) virus infection have significant health and economic consequences. Non-structural protein 1 (NS1) is an essential virulence factor of the highly pathogenic H5N1 avian influenza virus and of the apoptosis associated with the pathogenesis of H5N1. Previous studies have revealed that the NS1 protein is able to induce apoptosis via an extrinsic pathway. However, it remains unclear whether the intrinsic pathway is also associated with this apoptosis. The present study used a clone of the NS1 gene from avian influenza A/Jiangsu/1/2007 and observed the localization of the NS1 protein and cytochrome c release from mitochondria and the change of mitochondrial membrane potential (MMP) in lung cancer cells. Cytotoxicity was detected using an MTT assay and the number of apoptotic cells was counted using a flow cytometer. Following the isolation of mitochondria, western blotting was performed to compare cytochrome c release from the mitochondria in cells before and after apoptosis. The change of MMP was detected using JC-1 staining. Furthermore, the results reveal that the majority of the NS1 protein was localized in the cell nucleus, and that it may induce apoptosis of human lung epithelial cells. The apoptosis occurred with marked cytochrome c release from mitochondria and a change of the MMP. This indicated that the NS1 protein may be associated with apoptosis induced by an intrinsic mitochondrial pathway.",2017 Nov 28,"['Bian, Qian', 'Lu, Jing', 'Zhang, Li', 'Chi, Ying', 'Li, Yan', 'Guo, Hongxiong']",Exp Ther Med,,,True
c7a3699cbb6e8ea60edabb60c0407883e6ed33f2,PMC,"Chloroquine, a FDA-approved Drug, Prevents Zika Virus Infection and its Associated Congenital Microcephaly in Mice",http://dx.doi.org/10.1016/j.ebiom.2017.09.034,PMC5652284,29033372,CC BY-NC-ND,"Zika virus (ZIKV) has become a global public health emergency due to its rapidly expanding range and its ability to cause severe congenital defects such as microcephaly. However, there are no FDA-approved therapies or vaccines against ZIKV infection. Through our screening of viral entry inhibitors, we found that chloroquine (CQ), a commonly used antimalarial and a FDA-approved drug that has also been repurposed against other pathogens, could significantly inhibit ZIKV infection in vitro, by blocking virus internalization. We also demonstrated that CQ attenuates ZIKV-associated morbidity and mortality in mice. Finally, we proved that CQ protects fetal mice from microcephaly caused by ZIKV infection. Our methodology of focusing on previously identified antivirals in screens for effectiveness against ZIKV proved to be a rapid and efficient means of discovering new ZIKV therapeutics. Selecting drugs that were previously FDA-approved, such as CQ, also improves the likelihood that they may more quickly reach stages of clinical testing and use by the public.",2017 Sep 28,"['Li, Chunfeng', 'Zhu, Xingliang', 'Ji, Xue', 'Quanquin, Natalie', 'Deng, Yong-Qiang', 'Tian, Min', 'Aliyari, Roghiyh', 'Zuo, Xiangyang', 'Yuan, Ling', 'Afridi, Shabbir Khan', 'Li, Xiao-Feng', 'Jung, Jae U.', 'Nielsen-Saines, Karin', 'Qin, Frank Xiao-Feng', 'Qin, Cheng-Feng', 'Xu, Zhiheng', 'Cheng, Genhong']",EBioMedicine,,,False
cc977f7fb011becc54322dc88f6b6d417c7ecc00,PMC,Seasonal influenza vaccine effectiveness against laboratory-confirmed influenza in 2015–2016: a hospital-based test-negative case–control study in Lithuania,http://dx.doi.org/10.1136/bmjopen-2017-017835,PMC5652622,29018073,CC BY-NC,"OBJECTIVE: A case–control study was conducted to assess seasonal influenza vaccine effectiveness (SIVE) during the 2015–2016 influenza season. METHODS: A study was performed in three departments in Lithuania between 1 December 2015 and 1 May 2016. Data on demographic and clinical characteristics including influenza vaccination status were collected from the patients recommended to receive the seasonal influenza vaccine. Influenza virus infection was confirmed by multiplex reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Ninety-one (56.4%) of the 163 included subjects were ≥65 years old. Fifteen (9.2%) subjects were vaccinated against influenza at least 2 weeks before the onset of influenza symptoms, 12 of them were ≥65 years old. Of the 72 (44.2%) influenza virus positive cases, 65 (39.9%) were confirmed with influenza A (including 50 cases of influenza A(H1N1)pdm09), eight (4.9%) were confirmed with influenza B and one was a co-infection. Unadjusted SIVE against any influenza, influenza type A and influenza A(H1N1)pdm09 was 57% (95% CI −41% to 87%), 52% (95% CI −57% to 85%) and 70% (95% CI −43% to 94%) respectively. CONCLUSION: Although SIVE estimates were not statistically significant the point estimates suggest moderate effectiveness against influenza type A.",2017 Oct 10,"['Kuliese, Monika', 'Jancoriene, Ligita', 'Grimalauskaite, Rita', 'Zablockiene, Birute', 'Damuleviciene, Gyte', 'Velyvyte, Daiva', 'Lesauskaite, Vita', 'Ambrozaitis, Arvydas', 'Mickiene, Aukse', 'Gefenaite, Giedre']",BMJ Open,,,True
392c6a48ced66f6f260b305d4fddfac33a3774b4,PMC,Seasonal influenza vaccine effectiveness against laboratory-confirmed influenza in 2015–2016: a hospital-based test-negative case–control study in Lithuania,http://dx.doi.org/10.1136/bmjopen-2017-017835,PMC5652622,29018073,CC BY-NC,"OBJECTIVE: A case–control study was conducted to assess seasonal influenza vaccine effectiveness (SIVE) during the 2015–2016 influenza season. METHODS: A study was performed in three departments in Lithuania between 1 December 2015 and 1 May 2016. Data on demographic and clinical characteristics including influenza vaccination status were collected from the patients recommended to receive the seasonal influenza vaccine. Influenza virus infection was confirmed by multiplex reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Ninety-one (56.4%) of the 163 included subjects were ≥65 years old. Fifteen (9.2%) subjects were vaccinated against influenza at least 2 weeks before the onset of influenza symptoms, 12 of them were ≥65 years old. Of the 72 (44.2%) influenza virus positive cases, 65 (39.9%) were confirmed with influenza A (including 50 cases of influenza A(H1N1)pdm09), eight (4.9%) were confirmed with influenza B and one was a co-infection. Unadjusted SIVE against any influenza, influenza type A and influenza A(H1N1)pdm09 was 57% (95% CI −41% to 87%), 52% (95% CI −57% to 85%) and 70% (95% CI −43% to 94%) respectively. CONCLUSION: Although SIVE estimates were not statistically significant the point estimates suggest moderate effectiveness against influenza type A.",2017 Oct 10,"['Kuliese, Monika', 'Jancoriene, Ligita', 'Grimalauskaite, Rita', 'Zablockiene, Birute', 'Damuleviciene, Gyte', 'Velyvyte, Daiva', 'Lesauskaite, Vita', 'Ambrozaitis, Arvydas', 'Mickiene, Aukse', 'Gefenaite, Giedre']",BMJ Open,,,False
6eeb02ec74319ff5cdc9f2f7bbfe3c1a29a8dcb7,PMC,Seasonal influenza vaccine effectiveness against laboratory-confirmed influenza in 2015–2016: a hospital-based test-negative case–control study in Lithuania,http://dx.doi.org/10.1136/bmjopen-2017-017835,PMC5652622,29018073,CC BY-NC,"OBJECTIVE: A case–control study was conducted to assess seasonal influenza vaccine effectiveness (SIVE) during the 2015–2016 influenza season. METHODS: A study was performed in three departments in Lithuania between 1 December 2015 and 1 May 2016. Data on demographic and clinical characteristics including influenza vaccination status were collected from the patients recommended to receive the seasonal influenza vaccine. Influenza virus infection was confirmed by multiplex reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Ninety-one (56.4%) of the 163 included subjects were ≥65 years old. Fifteen (9.2%) subjects were vaccinated against influenza at least 2 weeks before the onset of influenza symptoms, 12 of them were ≥65 years old. Of the 72 (44.2%) influenza virus positive cases, 65 (39.9%) were confirmed with influenza A (including 50 cases of influenza A(H1N1)pdm09), eight (4.9%) were confirmed with influenza B and one was a co-infection. Unadjusted SIVE against any influenza, influenza type A and influenza A(H1N1)pdm09 was 57% (95% CI −41% to 87%), 52% (95% CI −57% to 85%) and 70% (95% CI −43% to 94%) respectively. CONCLUSION: Although SIVE estimates were not statistically significant the point estimates suggest moderate effectiveness against influenza type A.",2017 Oct 10,"['Kuliese, Monika', 'Jancoriene, Ligita', 'Grimalauskaite, Rita', 'Zablockiene, Birute', 'Damuleviciene, Gyte', 'Velyvyte, Daiva', 'Lesauskaite, Vita', 'Ambrozaitis, Arvydas', 'Mickiene, Aukse', 'Gefenaite, Giedre']",BMJ Open,,,False
582505fda401e9da61e9632a110b2e57806d2e61,PMC,Medical residents’ attitudes and emotions related to Middle East respiratory syndrome in Saudi Arabia: A cross-sectional study,http://dx.doi.org/10.15537/smj.2017.9.20626,PMC5654029,28889153,CC BY-NC-SA,"OBJECTIVES: To determine medical residents’ emotions, attitudes, and knowledge related to Middle East respiratory syndrome (MERS) outbreaks. METHODS: In this is a cross sectional study, self-administered questionnaires were distributed and collected before resident education activities in 4 tertiary hospitals in Riyadh, Kingdom of Saudi Arabia, between November 2015 and January 2016. The questionnaire included questions related to residents’ demographic data and their emotions, attitudes, and knowledge related to an MERS outbreak. RESULTS: Of the 228 participants analyzed, 85.5% believed their work put them at risk of infection, and two-thirds believed their family was exposed to a greater risk of infection. However, only 2.6% would change their job. Nearly half of the residents indicated that their hospital had a clear plan, and only 28% considered themselves not well prepared for an MERS outbreak. CONCLUSIONS: Our study highlights medical residents’ attitude and emotions related to MERS outbreaks. Residents’ concerns and emotions in relation to MERS should be considered in greater detail by hospital policymakers.",2017 Aug,"['Aldrees, Turki', 'Al Ghobain, Mohammed', 'Alenezi, Abdullah', 'Alqaryan, Saleh', 'Aldabeeb, Dana', 'Alotaibi, Najed', 'Alzahrani, Kamal', 'Alharethy, Sami']",Saudi Med J,,,True
a9ed744baa5ce70adff087cb1ce4e77afc969822,PMC,Leukemia/lymphoma‐related factor (LRF) exhibits stage‐ and context‐dependent transcriptional controls in the oligodendrocyte lineage and modulates remyelination,http://dx.doi.org/10.1002/jnr.24083,PMC5655903,28556945,CC BY-NC,"Leukemia/lymphoma‐related factor (LRF), a zinc‐finger transcription factor encoded by Zbtb7a, is a protooncogene that regulates differentiation in diverse cell lineages, and in the CNS, its function is relatively unexplored. This study is the first to examine the role of LRF in CNS pathology. We first examined LRF expression in a murine viral model of spinal cord demyelination with clinically relevant lesion characteristics. LRF was rarely expressed in oligodendrocyte progenitors (OP) yet, was detected in nuclei of the majority of oligodendrocytes in healthy adult CNS and during remyelination. Plp/CreER (T) :Zbtb7a (fl/fl) mice were then used with cuprizone demyelination to determine the effect of LRF knockdown on oligodendrocyte repopulation and remyelination. Cuprizone was given for 6 weeks to demyelinate the corpus callosum. Tamoxifen was administered at 4, 5, or 6 weeks after the start of cuprizone. Tamoxifen‐induced knockdown of LRF impaired remyelination during 3 or 6‐week recovery periods after cuprizone. LRF knockdown earlier within the oligodendrocyte lineage using NG2CreER (T) :Zbtb7a (fl/fl) mice reduced myelination after 6 weeks of cuprizone. LRF knockdown from either the Plp/CreER (T) line or the NG2CreER (T) line did not significantly change OP or oligodendrocyte populations. In vitro promoter assays demonstrated the potential for LRF to regulate transcription of myelin‐related genes and the notch target Hes5, which has been implicated in control of myelin formation and repair. In summary, in the oligodendrocyte lineage, LRF is expressed mainly in oligodendrocytes but is not required for oligodendrocyte repopulation of demyelinated lesions. Furthermore, LRF can modulate the extent of remyelination, potentially by contributing to interactions regulating transcription.",2017 Dec 30,"['Davidson, Nathan L.', 'Yu, Fengshan', 'Kijpaisalratana, Naruchorn', 'Le, Tuan Q.', 'Beer, Laurel A.', 'Radomski, Kryslaine L.', 'Armstrong, Regina C.']",J Neurosci Res,,,True
f1880ad327af15c85665a90198a7088d32390e34,PMC,A 12-year follow-up study of combined treatment of post-severe acute respiratory syndrome patients with femoral head necrosis,http://dx.doi.org/10.2147/TCRM.S140694,PMC5656358,29089773,CC BY-NC,"OBJECTIVE: To investigate the long-term efficacy of a combination treatment of alendronate, extracorporeal shock and hyperbaric oxygen for osteonecrosis of the femoral head (ONFH) of post-severe acute respiratory syndrome (SARS) patients. PATIENTS AND METHODS: The retrospective study was performed including a total of 37 post-SARS ONFH patients (66 hip joints) in the Department of Orthopedics of the General Hospital of Tianjin Medical University between November 2003 and November 2015, consisting of 6 males (11 hip joints) and 31 females (55 hip joints), with age between 19 and 47 years (average 29.9 years). Visual analog scale (VAS) score, Harris score and Association Research Circulation Osseous (ARCO) stage of imaging examination were compared among those before treatment, and at 1, 3, 6, 9 and 12 years after treatment. Paired t-test was used for statistical analysis of VAS and Harris score before and after treatment. Difference of effective rate on all stages was analyzed with Chi-square test. RESULTS: With 12-year follow-up, significant improvements on VAS (6.81 of pre-treatment vs 3.94 of 12-year post-treatment) and Harris score (74.54 of pre-treatment vs 80.14 of 12-year post-treatment) were observed (all p<0.05). Effective rate showed statistical significance among three stages of ARCO (p<0.05). The combined treatment showed different efficacies on different ARCO stages; the best was on ARCO Phase I. CONCLUSION: The combined treatment may delay or discontinue the development of ONFH in post-SARS patients.",2017 Oct 19,"['Liu, Tiansheng', 'Ma, Jinchao', 'Su, Bin', 'Wang, Hao', 'Wang, Qi', 'Ma, Xinlong']",Ther Clin Risk Manag,,,True
86db8aa209550ebe1e807a42ec268087be6ce826,PMC,Escaping Host Factor PI4KB Inhibition: Enterovirus Genomic RNA Replication in the Absence of Replication Organelles,http://dx.doi.org/10.1016/j.celrep.2017.09.068,PMC5656745,29045829,CC BY-NC-ND,"Enteroviruses reorganize cellular endomembranes into replication organelles (ROs) for genome replication. Although enterovirus replication depends on phosphatidylinositol 4-kinase type IIIβ (PI4KB), its role, and that of its product, phosphatidylinositol 4-phosphate (PI4P), is only partially understood. Exploiting a mutant coxsackievirus resistant to PI4KB inhibition, we show that PI4KB activity has distinct functions both in proteolytic processing of the viral polyprotein and in RO biogenesis. The escape mutation rectifies a proteolytic processing defect imposed by PI4KB inhibition, pointing to a possible escape mechanism. Remarkably, under PI4KB inhibition, the mutant virus could replicate its genome in the absence of ROs, using instead the Golgi apparatus. This impaired RO biogenesis provided an opportunity to investigate the proposed role of ROs in shielding enteroviral RNA from cellular sensors. Neither accelerated sensing of viral RNA nor enhanced innate immune responses was observed. Together, our findings challenge the notion that ROs are indispensable for enterovirus genome replication and immune evasion.",2017 Oct 17,"['Melia, Charlotte E.', 'van der Schaar, Hilde M.', 'Lyoo, Heyrhyoung', 'Limpens, Ronald W.A.L.', 'Feng, Qian', 'Wahedi, Maryam', 'Overheul, Gijs J.', 'van Rij, Ronald P.', 'Snijder, Eric J.', 'Koster, Abraham J.', 'Bárcena, Montserrat', 'van Kuppeveld, Frank J.M.']",Cell Rep,,,False
ee08ea83f740cad8dd0181e3ce4e788b471f08d1,PMC,Escaping Host Factor PI4KB Inhibition: Enterovirus Genomic RNA Replication in the Absence of Replication Organelles,http://dx.doi.org/10.1016/j.celrep.2017.09.068,PMC5656745,29045829,CC BY-NC-ND,"Enteroviruses reorganize cellular endomembranes into replication organelles (ROs) for genome replication. Although enterovirus replication depends on phosphatidylinositol 4-kinase type IIIβ (PI4KB), its role, and that of its product, phosphatidylinositol 4-phosphate (PI4P), is only partially understood. Exploiting a mutant coxsackievirus resistant to PI4KB inhibition, we show that PI4KB activity has distinct functions both in proteolytic processing of the viral polyprotein and in RO biogenesis. The escape mutation rectifies a proteolytic processing defect imposed by PI4KB inhibition, pointing to a possible escape mechanism. Remarkably, under PI4KB inhibition, the mutant virus could replicate its genome in the absence of ROs, using instead the Golgi apparatus. This impaired RO biogenesis provided an opportunity to investigate the proposed role of ROs in shielding enteroviral RNA from cellular sensors. Neither accelerated sensing of viral RNA nor enhanced innate immune responses was observed. Together, our findings challenge the notion that ROs are indispensable for enterovirus genome replication and immune evasion.",2017 Oct 17,"['Melia, Charlotte E.', 'van der Schaar, Hilde M.', 'Lyoo, Heyrhyoung', 'Limpens, Ronald W.A.L.', 'Feng, Qian', 'Wahedi, Maryam', 'Overheul, Gijs J.', 'van Rij, Ronald P.', 'Snijder, Eric J.', 'Koster, Abraham J.', 'Bárcena, Montserrat', 'van Kuppeveld, Frank J.M.']",Cell Rep,,,False
818d12fd5ffa6680a7624f66305538221c85300e,PMC,Ocular abnormalities associated with hypovitaminosis A in Hanwoo calves: a report of two cases,http://dx.doi.org/10.1292/jvms.17-0166,PMC5658573,28890472,CC BY-NC-ND,"This study reports on two Hanwoo (a native Korean breed of cattle) calves, a 3- and 6-month-old presenting with diarrhea, anorexia and blindness. Ophthalmoscopic examination revealed bilateral papilledema in both calves. Reverse-transcription polymerase chain reaction tests for bovine viral diarrhea virus, rotavirus and coronavirus were all negative. The levels of serum vitamin A in the two affected calves were 0.317 µg/dl and 0.481 µg/dl, respectively. These values are much lower than the normal vitamin A levels; therefore, the calves were diagnosed with hypovitaminosis A.",2017 Oct 8,"['KANG, Seonmi', 'PARK, Chanho', 'SEO, Kangmoon']",J Vet Med Sci,,,True
e6fcd7b5c6235d17f46c1721bd8695775f1df236,PMC,Time-series oligonucleotide count to assign antiviral siRNAs with long utility fit in the big data era,http://dx.doi.org/10.1038/gt.2017.76,PMC5658673,28905886,CC BY-NC-SA,"Oligonucleotides are key elements of nucleic acid therapeutics such as small interfering RNAs (siRNAs). Influenza and Ebolaviruses are zoonotic RNA viruses mutating very rapidly, and their sequence changes must be characterized intensively to design therapeutic oligonucleotides with long utility. Focusing on a total of 182 experimentally validated siRNAs for influenza A, B and Ebolaviruses compiled by the siRNA database, we conducted time-series analyses of occurrences of siRNA targets in these viral genomes. Reflecting their high mutation rates, occurrences of target oligonucleotides evidently fluctuate in viral populations and often disappear. Time-series analysis of the one-base changed sequences derived from each original target identified the oligonucleotide that shows a compensatory increase and will potentially become the ‘awaiting-type oligonucleotide’ the combined use of this oligonucleotide with the original can provide therapeutics with long utility. This strategy is also useful for assigning diagnostic reverse transcription-PCR primers with long utility.",2017 Oct 14,"['Wada, K', 'Wada, Y', 'Iwasaki, Y', 'Ikemura, T']",Gene Ther,,,True
5e44e7b19a93533bb6ac3683ff5a2f1e6e8c3524,PMC,Time-series oligonucleotide count to assign antiviral siRNAs with long utility fit in the big data era,http://dx.doi.org/10.1038/gt.2017.76,PMC5658673,28905886,CC BY-NC-SA,"Oligonucleotides are key elements of nucleic acid therapeutics such as small interfering RNAs (siRNAs). Influenza and Ebolaviruses are zoonotic RNA viruses mutating very rapidly, and their sequence changes must be characterized intensively to design therapeutic oligonucleotides with long utility. Focusing on a total of 182 experimentally validated siRNAs for influenza A, B and Ebolaviruses compiled by the siRNA database, we conducted time-series analyses of occurrences of siRNA targets in these viral genomes. Reflecting their high mutation rates, occurrences of target oligonucleotides evidently fluctuate in viral populations and often disappear. Time-series analysis of the one-base changed sequences derived from each original target identified the oligonucleotide that shows a compensatory increase and will potentially become the ‘awaiting-type oligonucleotide’ the combined use of this oligonucleotide with the original can provide therapeutics with long utility. This strategy is also useful for assigning diagnostic reverse transcription-PCR primers with long utility.",2017 Oct 14,"['Wada, K', 'Wada, Y', 'Iwasaki, Y', 'Ikemura, T']",Gene Ther,,,False
d7b736173972c7e1e61d44115b79fdb2e1b24a5d,PMC,Chemical Synthesis of the Highly Hydrophobic Antiviral Membrane‐Associated Protein IFITM3 and Modified Variants,http://dx.doi.org/10.1002/anie.201707554,PMC5658968,28834009,CC BY-NC-ND,"Interferon‐induced transmembrane protein 3 (IFITM3) is an antiviral transmembrane protein that is thought to serve as the primary factor for inhibiting the replication of a large number of viruses, including West Nile virus, Dengue virus, Ebola virus, and Zika virus. Production of this 14.5 kDa, 133‐residue transmembrane protein, especially with essential posttranslational modifications, by recombinant expression is challenging. In this report, we document the chemical synthesis of IFTIM3 in multi‐milligram quantities (>15 mg) and the preparation of phosphorylated and fluorescent variants. The synthesis was accomplished by using KAHA ligations, which operate under acidic aqueous/organic mixtures that excel at solubilizing even the exceptionally hydrophobic C‐terminal region of IFITM3. The synthetic material is readily incorporated into model vesicles and forms the basis for using synthetic, homogenous IFITM3 and its derivatives for further studying its structure and biological mode of action.",2017 Oct 2,"['Harmand, Thibault J.', 'Pattabiraman, Vijaya R.', 'Bode, Jeffrey W.']",Angew Chem Int Ed Engl,,,True
aa029dc2c3ba585c0f6a05b6a1cf54e5aa66073b,PMC,Chemical Synthesis of the Highly Hydrophobic Antiviral Membrane‐Associated Protein IFITM3 and Modified Variants,http://dx.doi.org/10.1002/anie.201707554,PMC5658968,28834009,CC BY-NC-ND,"Interferon‐induced transmembrane protein 3 (IFITM3) is an antiviral transmembrane protein that is thought to serve as the primary factor for inhibiting the replication of a large number of viruses, including West Nile virus, Dengue virus, Ebola virus, and Zika virus. Production of this 14.5 kDa, 133‐residue transmembrane protein, especially with essential posttranslational modifications, by recombinant expression is challenging. In this report, we document the chemical synthesis of IFTIM3 in multi‐milligram quantities (>15 mg) and the preparation of phosphorylated and fluorescent variants. The synthesis was accomplished by using KAHA ligations, which operate under acidic aqueous/organic mixtures that excel at solubilizing even the exceptionally hydrophobic C‐terminal region of IFITM3. The synthetic material is readily incorporated into model vesicles and forms the basis for using synthetic, homogenous IFITM3 and its derivatives for further studying its structure and biological mode of action.",2017 Oct 2,"['Harmand, Thibault J.', 'Pattabiraman, Vijaya R.', 'Bode, Jeffrey W.']",Angew Chem Int Ed Engl,,,True
7b0abf2414de3794e54ed37050884f636333972f,PMC,"What We Are Watching—Top Global Infectious Disease Threats, 2013-2016: An Update from CDC's Global Disease Detection Operations Center",http://dx.doi.org/10.1089/hs.2017.0004,PMC5661857,28805465,CC BY-NC,"To better track public health events in areas where the public health system is unable or unwilling to report the event to appropriate public health authorities, agencies can conduct event-based surveillance, which is defined as the organized collection, monitoring, assessment, and interpretation of unstructured information regarding public health events that may represent an acute risk to public health. The US Centers for Disease Control and Prevention's (CDC's) Global Disease Detection Operations Center (GDDOC) was created in 2007 to serve as CDC's platform dedicated to conducting worldwide event-based surveillance, which is now highlighted as part of the “detect” element of the Global Health Security Agenda (GHSA). The GHSA works toward making the world more safe and secure from disease threats through building capacity to better “Prevent, Detect, and Respond” to those threats. The GDDOC monitors approximately 30 to 40 public health events each day. In this article, we describe the top threats to public health monitored during 2012 to 2016: avian influenza, cholera, Ebola virus disease, and the vector-borne diseases yellow fever, chikungunya virus, and Zika virus, with updates to the previously described threats from Middle East respiratory syndrome-coronavirus (MERS-CoV) and poliomyelitis.",2017 Oct 1,"['Christian, Kira A.', 'Iuliano, A. Danielle', 'Uyeki, Timothy M.', 'Mintz, Eric D.', 'Nichol, Stuart T.', 'Rollin, Pierre', 'Staples, J. Erin', 'Arthur, Ray R.']",Health Secur,,,True
3c39d9aa9e05723ab781cc800c89c69869fd0eeb,PMC,Host Cell Vimentin Restrains Toxoplasma gondii Invasion and Phosphorylation of Vimentin is Partially Regulated by Interaction with TgROP18,http://dx.doi.org/10.7150/ijbs.21247,PMC5666328,29104504,CC BY-NC,"The obligate intracellular parasite, Toxoplasma gondii, manipulates the cytoskeleton of its host cells to facilitate infection. A significant rearrangement of host cell vimentin around Toxoplasma parasitophorous vacuoles is observed during the course of infection. ROP18 (TgROP18) is a serine-threonine kinase secreted by T. gondii rhoptry and a major virulence factor; however, the mechanisms by which this kinase modulates host factors remain poorly understood. Different and dynamic patterns of vimentin solubility, phosphorylation, and expression levels were observed in host cells infected with T. gondii strain RH and RH Δrop18 strains, suggesting that TgROP18 contributes to the regulation of these dynamic patterns. Additionally, host cell vimentin was demonstrated to interact with and be phosphorylated by TgROP18. A significant increase in T. gondii infection rate was observed in vimentin knockout human brain microvessel endothelial cells (HBMEC), while vimentin knockout or knock down in host cells had no impact on parasite proliferation and egress. These results indicate that host cell vimentin can inhibit T. gondii invasion. Interestingly, western blotting of different mouse tissues indicated that the lowest vimentin expression level was present in the brain, which may explain the mechanism underlying the nervous system tropism of T. gondii, and the phenomenon of huge cyst burdens developing in the mouse brain during chronic infection.",2017 Sep 5,"['He, Cheng', 'Kong, Ling', 'Zhou, Lijuan', 'Xia, Jing', 'Wei, Haixia', 'Liu, Min', 'Peng, Hongjuan']",Int J Biol Sci,,,True
8d487139eb8085addba9850f90597f206531f3c9,PMC,Host Cell Vimentin Restrains Toxoplasma gondii Invasion and Phosphorylation of Vimentin is Partially Regulated by Interaction with TgROP18,http://dx.doi.org/10.7150/ijbs.21247,PMC5666328,29104504,CC BY-NC,"The obligate intracellular parasite, Toxoplasma gondii, manipulates the cytoskeleton of its host cells to facilitate infection. A significant rearrangement of host cell vimentin around Toxoplasma parasitophorous vacuoles is observed during the course of infection. ROP18 (TgROP18) is a serine-threonine kinase secreted by T. gondii rhoptry and a major virulence factor; however, the mechanisms by which this kinase modulates host factors remain poorly understood. Different and dynamic patterns of vimentin solubility, phosphorylation, and expression levels were observed in host cells infected with T. gondii strain RH and RH Δrop18 strains, suggesting that TgROP18 contributes to the regulation of these dynamic patterns. Additionally, host cell vimentin was demonstrated to interact with and be phosphorylated by TgROP18. A significant increase in T. gondii infection rate was observed in vimentin knockout human brain microvessel endothelial cells (HBMEC), while vimentin knockout or knock down in host cells had no impact on parasite proliferation and egress. These results indicate that host cell vimentin can inhibit T. gondii invasion. Interestingly, western blotting of different mouse tissues indicated that the lowest vimentin expression level was present in the brain, which may explain the mechanism underlying the nervous system tropism of T. gondii, and the phenomenon of huge cyst burdens developing in the mouse brain during chronic infection.",2017 Sep 5,"['He, Cheng', 'Kong, Ling', 'Zhou, Lijuan', 'Xia, Jing', 'Wei, Haixia', 'Liu, Min', 'Peng, Hongjuan']",Int J Biol Sci,,,True
636a2debbb56c9142bbf960d9a200665c556e05a,PMC,Multiplexed Nucleic Acid Programmable Protein Arrays,http://dx.doi.org/10.7150/thno.20151,PMC5667425,29109798,CC BY-NC,"Rationale: Cell-free protein microarrays display naturally-folded proteins based on just-in-time in situ synthesis, and have made important contributions to basic and translational research. However, the risk of spot-to-spot cross-talk from protein diffusion during expression has limited the feature density of these arrays. Methods: In this work, we developed the Multiplexed Nucleic Acid Programmable Protein Array (M-NAPPA), which significantly increases the number of displayed proteins by multiplexing as many as five different gene plasmids within a printed spot. Results: Even when proteins of different sizes were displayed within the same feature, they were readily detected using protein-specific antibodies. Protein-protein interactions and serological antibody assays using human viral proteome microarrays demonstrated that comparable hits were detected by M-NAPPA and non-multiplexed NAPPA arrays. An ultra-high density proteome microarray displaying > 16k proteins on a single microscope slide was produced by combining M-NAPPA with a photolithography-based silicon nano-well platform. Finally, four new tuberculosis-related antigens in guinea pigs vaccinated with Bacillus Calmette-Guerin (BCG) were identified with M-NAPPA and validated with ELISA. Conclusion: All data demonstrate that multiplexing features on a protein microarray offer a cost-effective fabrication approach and have the potential to facilitate high throughput translational research.",2017 Sep 20,"['Yu, Xiaobo', 'Song, Lusheng', 'Petritis, Brianne', 'Bian, Xiaofang', 'Wang, Haoyu', 'Viloria, Jennifer', 'Park, Jin', 'Bui, Hoang', 'Li, Han', 'Wang, Jie', 'Liu, Lei', 'Yang, Liuhui', 'Duan, Hu', 'McMurray, David N.', 'Achkar, Jacqueline M.', 'Magee, Mitch', 'Qiu, Ji', 'LaBaer, Joshua']",Theranostics,,,True
c3d625e2679a849bc3c15f06effe9ba6597b4b13,PMC,Multiplexed Nucleic Acid Programmable Protein Arrays,http://dx.doi.org/10.7150/thno.20151,PMC5667425,29109798,CC BY-NC,"Rationale: Cell-free protein microarrays display naturally-folded proteins based on just-in-time in situ synthesis, and have made important contributions to basic and translational research. However, the risk of spot-to-spot cross-talk from protein diffusion during expression has limited the feature density of these arrays. Methods: In this work, we developed the Multiplexed Nucleic Acid Programmable Protein Array (M-NAPPA), which significantly increases the number of displayed proteins by multiplexing as many as five different gene plasmids within a printed spot. Results: Even when proteins of different sizes were displayed within the same feature, they were readily detected using protein-specific antibodies. Protein-protein interactions and serological antibody assays using human viral proteome microarrays demonstrated that comparable hits were detected by M-NAPPA and non-multiplexed NAPPA arrays. An ultra-high density proteome microarray displaying > 16k proteins on a single microscope slide was produced by combining M-NAPPA with a photolithography-based silicon nano-well platform. Finally, four new tuberculosis-related antigens in guinea pigs vaccinated with Bacillus Calmette-Guerin (BCG) were identified with M-NAPPA and validated with ELISA. Conclusion: All data demonstrate that multiplexing features on a protein microarray offer a cost-effective fabrication approach and have the potential to facilitate high throughput translational research.",2017 Sep 20,"['Yu, Xiaobo', 'Song, Lusheng', 'Petritis, Brianne', 'Bian, Xiaofang', 'Wang, Haoyu', 'Viloria, Jennifer', 'Park, Jin', 'Bui, Hoang', 'Li, Han', 'Wang, Jie', 'Liu, Lei', 'Yang, Liuhui', 'Duan, Hu', 'McMurray, David N.', 'Achkar, Jacqueline M.', 'Magee, Mitch', 'Qiu, Ji', 'LaBaer, Joshua']",Theranostics,,,False
f98e165a9cb60bc2e32686ceb4ed188425fbc318,PMC,Knowledge and awareness of Middle East respiratory syndrome coronavirus among Saudi and Non-Saudi Arabian pilgrims,,PMC5669506,29114190,CC BY-NC-SA,"OBJECTIVE: The current study was intended to evaluate the knowledge and awareness toward Middle East respiratory syndrome coronavirus (MERS-CoV) of pilgrims from Saudi Arabia and from different Arabian countries. METHODS: A prospective study was conducted among pilgrims from Saudi Arabia and those from other Arab nations. A total number of 2120 participants including 736 Saudi pilgrims (436 males and 300 females) and 1384 non-Saudi Arabian pilgrims (1384; 909 males and 475 females) were included in the study. The responses of the participants were descriptively analyzed. Pearson correlation coefficient was used to screen the possible correlations among different variables. The differences in the responses between the two groups were evaluated using Mann–Whitney analysis. RESULTS: The responses of the Saudi pilgrims showed statistically significant results in comparison to non-Saudi pilgrims in answering all questions except those related to the presence of efficient vaccination or treatment and the source of information. It was clear that the Saudi pilgrims were more oriented about different aspects of MERS-CoV including the nature of the causative agent, the signs, the severity of the disease, the animals that can transmit the infection to humans, the risk groups, and when one need to be screened for infection. In both Saudi and non-Saudi pilgrims, the official websites of health organizations constitute the main source of their information. CONCLUSION: It was concluded that Saudi pilgrims possess good knowledge about the MERS-CoV although more orientation is still required.",2017 Nov-Dec,"['Althobaity, Hosam M.', 'Alharthi, Raed A. S.', 'Altowairqi, Mohammed H.', 'Alsufyani, Ziyad A.', 'Aloufi, Nahar S.', 'Altowairqi, Abdulrahman E.', 'Alqahtani, Abdulrahman S.', 'Alzahrani, Ali K.', 'Abdel-Moneim, Ahmed S.']",Int J Health Sci (Qassim),,,True
650c04938724d08709151733994c22ddd00b68aa,PMC,Signatures of Nucleotide Analog Incorporation by an RNA-Dependent RNA Polymerase Revealed Using High-Throughput Magnetic Tweezers,http://dx.doi.org/10.1016/j.celrep.2017.10.005,PMC5670035,29069588,CC BY-NC-ND,"RNA viruses pose a threat to public health that is exacerbated by the dearth of antiviral therapeutics. The RNA-dependent RNA polymerase (RdRp) holds promise as a broad-spectrum, therapeutic target because of the conserved nature of the nucleotide-substrate-binding and catalytic sites. Conventional, quantitative, kinetic analysis of antiviral ribonucleotides monitors one or a few incorporation events. Here, we use a high-throughput magnetic tweezers platform to monitor the elongation dynamics of a prototypical RdRp over thousands of nucleotide-addition cycles in the absence and presence of a suite of nucleotide analog inhibitors. We observe multiple RdRp-RNA elongation complexes; only a subset of which are competent for analog utilization. Incorporation of a pyrazine-carboxamide nucleotide analog, T-1106, leads to RdRp backtracking. This analysis reveals a mechanism of action for this antiviral ribonucleotide that is corroborated by cellular studies. We propose that induced backtracking represents a distinct mechanistic class of antiviral ribonucleotides.",2017 Oct 24,"['Dulin, David', 'Arnold, Jamie J.', 'van Laar, Theo', 'Oh, Hyung-Suk', 'Lee, Cheri', 'Perkins, Angela L.', 'Harki, Daniel A.', 'Depken, Martin', 'Cameron, Craig E.', 'Dekker, Nynke H.']",Cell Rep,,,False
9f9ca5a0edfc1a2fd8f5b87bd84f332dc06a20e0,PMC,Signatures of Nucleotide Analog Incorporation by an RNA-Dependent RNA Polymerase Revealed Using High-Throughput Magnetic Tweezers,http://dx.doi.org/10.1016/j.celrep.2017.10.005,PMC5670035,29069588,CC BY-NC-ND,"RNA viruses pose a threat to public health that is exacerbated by the dearth of antiviral therapeutics. The RNA-dependent RNA polymerase (RdRp) holds promise as a broad-spectrum, therapeutic target because of the conserved nature of the nucleotide-substrate-binding and catalytic sites. Conventional, quantitative, kinetic analysis of antiviral ribonucleotides monitors one or a few incorporation events. Here, we use a high-throughput magnetic tweezers platform to monitor the elongation dynamics of a prototypical RdRp over thousands of nucleotide-addition cycles in the absence and presence of a suite of nucleotide analog inhibitors. We observe multiple RdRp-RNA elongation complexes; only a subset of which are competent for analog utilization. Incorporation of a pyrazine-carboxamide nucleotide analog, T-1106, leads to RdRp backtracking. This analysis reveals a mechanism of action for this antiviral ribonucleotide that is corroborated by cellular studies. We propose that induced backtracking represents a distinct mechanistic class of antiviral ribonucleotides.",2017 Oct 24,"['Dulin, David', 'Arnold, Jamie J.', 'van Laar, Theo', 'Oh, Hyung-Suk', 'Lee, Cheri', 'Perkins, Angela L.', 'Harki, Daniel A.', 'Depken, Martin', 'Cameron, Craig E.', 'Dekker, Nynke H.']",Cell Rep,,,False
89d4bbbaafc5df5274e5ca4f2b21b3f27b50b216,PMC,"Corticosteroid-induced Osteonecrosis of the Femoral Head: Detection, Diagnosis, and Treatment in Earlier Stages",http://dx.doi.org/10.4103/0366-6999.217094,PMC5678261,29067959,CC BY-NC-SA,"OBJECTIVE: This review aimed to provide a current recommendation to multidisciplinary physicians for early detection, diagnosis, and treatment of corticosteroid-induced osteonecrosis of the femoral head (ONFH) based on a comprehensive analysis of the clinical literature. DATA SOURCES: For the purpose of collecting potentially eligible articles, we searched for articles in the PubMed, Cochrane Library, Embase, and CNKI databases up to February 2017, using the following key words: “corticosteroid”, “osteonecrosis of the femoral head”, “risk factors”, “diagnosis”, “prognosis”, and “treatment”. STUDY SELECTION: Articles on relationships between corticosteroid and ONFH were selected for this review. Articles on the diagnosis, prognosis, and intervention of earlier-stage ONFH were also reviewed. RESULTS: The incidence of corticosteroid-induced ONFH was associated with high doses of corticosteroids, and underlying diseases in certain predisposed individuals mainly occurred in the first 3 months of corticosteroid prescription. The enhanced awareness and minimized exposure to the established risk factors and earlier definitive diagnosis are essential for the success of joint preservation. When following up patients with ONFH, treatment should be started if necessary. Surgical treatment yielded better results than conservative therapy in earlier-stage ONFH. The ideal purpose of earlier intervention and treatment is permanent preservation of the femoral head without physical restrictions in daily living. CONCLUSIONS: Clinicians should enhance their precaution awareness of corticosteroid-induced ONFH. For high-risk patients, regular follow-up is very important in the 1(st) year after high-dose prescription of corticosteroids. Patients with suspected ONFH should be referred to orthopedists for diagnosis and treatment in its earlier stage to preserve the joint.",2017 Nov 5,"['Liu, Li-Hua', 'Zhang, Qing-Yu', 'Sun, Wei', 'Li, Zi-Rong', 'Gao, Fu-Qiang']",Chin Med J (Engl),,,True
b05c7d68086daf67e216e3df0ae0477343632d03,PMC,Influence of age and body condition on astrovirus infection of bats in Singapore: An evolutionary and epidemiological analysis,http://dx.doi.org/10.1016/j.onehlt.2017.10.001,PMC5678831,29159263,CC BY-NC-ND,"Bats are unique mammals that are reservoirs of high levels of virus diversity. Although several of these viruses are zoonotic, the majority are not. Astroviruses, transmitted fecal-orally, are commonly detected in a wide diversity of bat species, are prevalent at high rates and are not thought to directly infect humans. These features make astroviruses useful in examining virus evolutionary history, epidemiology in the host, and temporal shedding trends. Our study screened for the presence of astroviruses in bats in Singapore, reconstructed the phylogenetic relations of the polymerase genes and tested for population characteristics associated with infection. Of the seven species screened, astroviruses were detected in Rhinolophus lepidus and Eonycteris spelaea. The R. lepidus sequences grouped with other Rhinolophus astrovirus sequences from China and Laos, while the Eoncyteris sequences formed a distinct clade with astroviruses from Rousettus spp. in Laos and Pteropus giganteus in Bangladesh, but not with other E. spelaea sequences. Longitudinal collections of Eonycteris feces demonstrated variable shedding. Juvenile status of bats was a risk factor for astroviruses. This study highlights the diversity of astroviruses in nectivorous and insectivorous bats in Singapore and provides a predictive framework for understanding astrovirus infection in these bats. It also suggests that in addition to host phylogenetic relatedness, host ecology, such as roosting behavior, may drive co-infections, virus maintenance and spillover.",2017 Oct 6,"['Mendenhall, Ian H.', 'Skiles, Maggie M.', 'Neves, Erica Sena', 'Borthwick, Sophie A.', 'Low, Dolyce H.W.', 'Liang, Benjamin', 'Lee, Benjamin P.Y.-H.', 'Su, Yvonne C.F.', 'Smith, Gavin J.D.']",One Health,,,False
0aa3eda0fb09bf9f55864fc2b9157b9317f62323,PMC,Epidemiological surveillance of land borders in North and South America: a case study,http://dx.doi.org/10.1590/S1678-9946201759068,PMC5679680,29116288,CC BY-NC,"This study aims to analyze the different binational/multinational activities, programs, and structures taking place on the borders of Brazil and the U.S. between 2013 and 2015. A descriptive exploratory study of two border epidemiological surveillance (BES) systems has been performed. Two approaches were used to collect data: i) technical visits to the facilities involved with border surveillance and application of a questionnaire survey; ii) application of an online questionnaire survey. It was identified that, for both surveillance systems, more than 55% of the technicians had realized that the BES and its activities have high priority. Eighty percent of North American and 71% of Brazilian border jurisdictions reported an exchange of information between countries. Less than half of the jurisdictions reported that the necessary tools to carry out information exchange were available. Operational attributes of completeness, feedback, reciprocity, and quality of information were identified as weak or of low quality in both systems. Statements, guidelines, and protocols to develop surveillance activities are available at the U.S.-Mexico border area. The continuous systematic development of surveillance systems at these borders will create more effective actions and responses.",2017 Nov 6,"['Bruniera-Oliveira, Robson', 'Horta, Marco Aurélio Pereira', 'Varan, Aiden', 'Montiel, Sonia', 'Carmo, Eduardo Hage', 'Waterman, Stephen H', 'Verani, José Fernando de Souza']",Rev Inst Med Trop Sao Paulo,,,True
5f071d0350cb9013deb98f9a52070bbf0f70bb84,PMC,Cytokines Interleukin 4 (IL-4) and Interleukin 10 (IL-10) Gene Polymorphisms as Potential Host Susceptibility Factors in Virus-Induced Encephalitis,http://dx.doi.org/10.12659/MSM.904364,PMC5683680,28935853,CC BY-NC-ND,"BACKGROUND: This study aimed to analyze and explore the relationship between the cytokines IL-4 and IL-10 in relation to gene polymorphism and their respective effects on the susceptibility to virus-induced encephalitis. MATERIAL/METHODS: From January 2012 to June 2013, 112 patients with virus-induced encephalitis (the case group and 109 healthy individuals (the control group) were recruited for the purposes of this study. The functional variations that IL-4 and IL-10 genes exhibit were detected through the use of a function analysis and selection tool for single-nucleotide polymorphisms (FASTSNP). The genotypes of IL-4 were rs2227283 and IL-4 rs2227288, and the genotypes of IL-10 were rs1800871 and IL-10 rs1800872. These genotypes were respectively assessed using direct sequencing. RESULTS: IL-4 rs2227283 and IL-10 rs1800871 have no correlation in with risk of virus-induced encephalitis (both P>0.05) GA and AA genotypes were related to IL-4 rs2227288 and GT, while TT and GT + TT genotypes were related to IL-10 rs1800872. These were highlighted as being risk factors in virus-induced encephalitis (all P<0.05). However, the duration of fever, white blood cell (WBC) count, C-reactive protein (CRP), neutrophils, and lymphocytes and monocytes of virus-induced encephalitis patients with IL-4 rs2227288 and IL-10 rs1800872 all displayed significant differences (all P<0.05). Frequencies of GAGT and CAGT haplotypes were evaluated and deemed to be of statistical significance and subsequently were highlighted as being risk factors in virus-induced encephalitis (all P<0.05). CONCLUSIONS: IL-4 rs2227288 and IL-10 rs1800872 may contribute to an increased risk for virus-induced encephalitis. Through use of direct sequencing, we showed that genotypes of IL-4 rs2227288 and IL-10 rs1800872 may have particular host susceptibility to virus-induced encephalitis.",2017 Sep 22,"['Yu, Ying', 'Chen, Ying', 'Wang, Feng-Ling', 'Sun, Jing', 'Li, Hai-Jun', 'Liu, Jia-Ming']",Med Sci Monit,,,True
7096c575274ae29d1398ec04938f568e5187c9a1,PMC,Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1126/sciadv.aao4966,PMC5687858,29152574,CC BY-NC,"Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication. We also identified the evidence of enteric MERS-CoV infection in the stool specimen of a clinical patient. MERS-CoV was considerably resistant to fed-state gastrointestinal fluids but less tolerant to highly acidic fasted-state gastric fluid. In polarized Caco-2 cells cultured in Transwell inserts, apical MERS-CoV inoculation was more effective in establishing infection than basolateral inoculation. Notably, direct intragastric inoculation of MERS-CoV caused a lethal infection in human DPP4 transgenic mice. Histological examination revealed MERS-CoV enteric infection in all inoculated mice, as shown by the presence of virus-positive cells, progressive inflammation, and epithelial degeneration in small intestines, which were exaggerated in the mice pretreated with the proton pump inhibitor pantoprazole. With the progression of the enteric infection, inflammation, virus-positive cells, and live viruses emerged in the lung tissues, indicating the development of sequential respiratory infection. Taken together, these data suggest that the human intestinal tract may serve as an alternative infection route for MERS-CoV.",2017 Nov 15,"['Zhou, Jie', 'Li, Cun', 'Zhao, Guangyu', 'Chu, Hin', 'Wang, Dong', 'Yan, Helen Hoi-Ning', 'Poon, Vincent Kwok-Man', 'Wen, Lei', 'Wong, Bosco Ho-Yin', 'Zhao, Xiaoyu', 'Chiu, Man Chun', 'Yang, Dong', 'Wang, Yixin', 'Au-Yeung, Rex K. H.', 'Chan, Ivy Hau-Yee', 'Sun, Shihui', 'Chan, Jasper Fuk-Woo', 'To, Kelvin Kai-Wang', 'Memish, Ziad A.', 'Corman, Victor M.', 'Drosten, Christian', 'Hung, Ivan Fan-Ngai', 'Zhou, Yusen', 'Leung, Suet Yi', 'Yuen, Kwok-Yung']",Sci Adv,,,True
1d3cf8875813bb56f4d5df8c11d0785ddeaf1a99,PMC,Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1126/sciadv.aao4966,PMC5687858,29152574,CC BY-NC,"Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication. We also identified the evidence of enteric MERS-CoV infection in the stool specimen of a clinical patient. MERS-CoV was considerably resistant to fed-state gastrointestinal fluids but less tolerant to highly acidic fasted-state gastric fluid. In polarized Caco-2 cells cultured in Transwell inserts, apical MERS-CoV inoculation was more effective in establishing infection than basolateral inoculation. Notably, direct intragastric inoculation of MERS-CoV caused a lethal infection in human DPP4 transgenic mice. Histological examination revealed MERS-CoV enteric infection in all inoculated mice, as shown by the presence of virus-positive cells, progressive inflammation, and epithelial degeneration in small intestines, which were exaggerated in the mice pretreated with the proton pump inhibitor pantoprazole. With the progression of the enteric infection, inflammation, virus-positive cells, and live viruses emerged in the lung tissues, indicating the development of sequential respiratory infection. Taken together, these data suggest that the human intestinal tract may serve as an alternative infection route for MERS-CoV.",2017 Nov 15,"['Zhou, Jie', 'Li, Cun', 'Zhao, Guangyu', 'Chu, Hin', 'Wang, Dong', 'Yan, Helen Hoi-Ning', 'Poon, Vincent Kwok-Man', 'Wen, Lei', 'Wong, Bosco Ho-Yin', 'Zhao, Xiaoyu', 'Chiu, Man Chun', 'Yang, Dong', 'Wang, Yixin', 'Au-Yeung, Rex K. H.', 'Chan, Ivy Hau-Yee', 'Sun, Shihui', 'Chan, Jasper Fuk-Woo', 'To, Kelvin Kai-Wang', 'Memish, Ziad A.', 'Corman, Victor M.', 'Drosten, Christian', 'Hung, Ivan Fan-Ngai', 'Zhou, Yusen', 'Leung, Suet Yi', 'Yuen, Kwok-Yung']",Sci Adv,,,False
a183646896ed073a4ec4035c5b6c6c77db89f0b3,PMC,Methods Using Social Media and Search Queries to Predict Infectious Disease Outbreaks,http://dx.doi.org/10.4258/hir.2017.23.4.343,PMC5688036,29181246,CC BY-NC,"OBJECTIVES: For earlier detection of infectious disease outbreaks, a digital syndromic surveillance system based on search queries or social media should be utilized. By using real-time data sources, a digital syndromic surveillance system can overcome the limitation of time-delay in traditional surveillance systems. Here, we introduce an approach to develop such a digital surveillance system. METHODS: We first explain how the statistics data of infectious diseases, such as influenza and Middle East Respiratory Syndrome (MERS) in Korea, can be collected for reference data. Then we also explain how search engine queries can be retrieved from Google Trends. Finally, we describe the implementation of the prediction model using lagged correlation, which can be calculated by the statistical packages, i.e., SPSS (Statistical Package for the Social Sciences). RESULTS: Lag correlation analyses demonstrated that search engine data/Twitter have a significant temporal relationship with influenza and MERS data. Therefore, the proposed digital surveillance system can be used to predict infectious disease outbreaks earlier. CONCLUSIONS: This prediction method could be the core engine for implementing a (near-) real-time digital surveillance system. A digital surveillance system that uses Internet resources has enormous potential to monitor disease outbreaks in the early phase.",2017 Oct 31,"['Seo, Dong-Woo', 'Shin, Soo-Yong']",Healthc Inform Res,,,True
0ae7bedff3dfbfc1ccaeb5b662bbace00ae16b33,PMC,Follow-up monitoring in a cat with leishmaniosis and coinfections with Hepatozoon felis and ‘Candidatus Mycoplasma haemominutum’,http://dx.doi.org/10.1177/2055116917740454,PMC5692141,29163980,CC BY-NC,"CASE SUMMARY: A 6-year-old female neutered domestic shorthair cat from Cyprus was presented with multiple ulcerated skin nodules. Cytology and histopathology of the lesions revealed granulomatous dermatitis with intracytoplasmic organisms, consistent with amastigotes of Leishmania species. Biochemistry identified a mild hyperproteinaemia. Blood extraction and PCR detected Leishmania species, Hepatozoon species and ‘Candidatus Mycoplasma haemominutum’ (CMhm) DNA. Subsequent sequencing identified Hepatozoon felis. Additionally, the rRNA internal transcribed spacer 1 locus of Leishmania infantum was partially sequenced and phylogeny showed it to cluster with species derived from dogs in Italy and Uzbekistan, and a human in France. Allopurinol treatment was administered for 6 months. Clinical signs resolved in the second month of treatment with no deterioration 8 months post-treatment cessation. Quantitative PCR and ELISA were used to monitor L infantum blood DNA and antibody levels. The cat had high L infantum DNA levels pretreatment that gradually declined during treatment but increased 8 months post-treatment cessation. Similarly, ELISA revealed high levels of antibodies pretreatment, which gradually declined during treatment and increased slightly 8 months post-treatment cessation. The cat remained PCR positive for CMhm and Hepatozoon species throughout the study. There was no clinical evidence of relapse 24 months post-treatment. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first clinical report of a cat with leishmaniosis with H felis and CMhm coinfections. The high L infantum DNA levels post-treatment cessation might indicate that although the lesions had resolved, prolonged or an alternative treatment could have been considered.",2017 Nov 14,"['Attipa, Charalampos', 'Neofytou, Kyriaki', 'Yiapanis, Christos', 'Martínez-Orellana, Pamela', 'Baneth, Gad', 'Nachum-Biala, Yaarit', 'Brooks-Brownlie, Harriet', 'Solano-Gallego, Laia', 'Tasker, Séverine']",JFMS Open Rep,,,True
34a7701ed25e68579ebbc78052c369ba29bc1fae,PMC,Detection of Bovine Coronavirus in Healthy and Diarrheic Dairy Calves,http://dx.doi.org/10.1111/jvim.14811,PMC5697193,28913936,CC BY-NC,"BACKGROUND: BCoV is identified in both healthy and diarrheic calves, complicating its assessment as a primary pathogen. OBJECTIVES: To investigate the detection rates of bovine coronavirus (BCoV) in feces of healthy and diarrheic calves and to describe the usefulness of a pancoronavirus reverse transcriptase (RT) PCR (PanCoV‐RT‐PCR) assay to identify BCoV in samples of diarrheic calves. ANIMALS: Two hundred and eighty‐six calves <21 days. Calves with liquid or semiliquid feces, temperature >39.5°C, and inappetence were considered as cases, and those that had pasty or firm feces and normal physical examination were designated as controls. METHODS: Prospective case–control study. A specific BCoV‐RT‐PCR assay was used to detect BCoV in fecal samples. Association between BCoV and health status was evaluated by exact and random effect logistic regression. Fecal (n = 28) and nasal (n = 8) samples from diarrheic calves were tested for the presence of BCoV by both the PanCoV‐RT‐PCR and a specific BCoV‐RT‐PCR assays. A Kappa coefficient test was used to assess the level of agreement of both assays. RESULTS: BCoV was detected in 55% (157/286) of calves; 46% (66/143), and 64% (91/143) of healthy and diarrheic calves, respectively. Diarrheic calves had higher odds of BCoV presence than healthy calves (OR: 2.16, 95% CI: 1.26 to 3.83, P = 0.004). A good agreement between PanCoV‐RT‐PCR and BCoV‐RT‐PCR to detect BCoV was identified (κ = 0.68, 95% CI: 0.392 to 0.967; P < 0.001). CONCLUSIONS AND CLINICAL IMPORTANCE: BCoV was more likely to be detected in diarrheic than healthy calves. The PanCoV‐RT‐PCR assay can be a useful tool to detect CoV samples from diarrheic calves.",2017 Sep 15 Nov-Dec,"['Gomez, D.E.', 'Arroyo, L.G.', 'Poljak, Z.', 'Viel, L.', 'Weese, J.S.']",J Vet Intern Med,,,True
82dcb53e236df1adb5c3c9f5291dc4e8eabb354a,PMC,Pathogen screening and prognostic factors in children with severe ARDS of pulmonary origin,http://dx.doi.org/10.1002/ppul.23694,PMC5697698,28703486,CC BY-NC,"BACKGROUND: Acute respiratory distress syndrome (ARDS) is one of the most lethal diseases encountered in the pediatric intensive care unit (PICU). The etiological pathogens and prognostic factors of severe ARDS of pulmonary origin in children with respiratory virus infections were prospectively investigated. METHODS: Enrolled children fulfilled the following criteria: (1) PICU admission; (2) age of 1 month to 16 years; (3) diagnosis of infectious pneumonia and respiratory virus infection; and (4) development of severe ARDS within 72 h after PICU admission. Pathogens were detected in the blood and tracheal lavage fluid using molecular techniques and a conventional culture system. The serum levels of inflammatory mediators on the day of PICU admission were examined. RESULTS: Fifty‐seven patients (32 boys; median age, 9 months) were enrolled. Multiple virus infections, co‐infection with bacteria/fungus, and bacteremia/fungemia were observed in 60%, 49%, and 32% of children, respectively. Adenovirus‐B, measles virus, and cytomegalovirus were detected predominantly in tracheal lavage fluid. There were no statistically significant differences between non‐survivors and survivors regarding the types of pathogen, incidence of multiple virus infection, gender, age, clinical features, and treatment. The serum levels of interferon (IFN)‐γ and the IFN‐γ/interleukin (IL)‐10 ratio were higher in non‐survivors. CONCLUSIONS: IFN‐γ upregulation as detected on the day of PICU admission was found to be one of the possible prognostic factors affecting a fatal outcome. These results suggest that modulation of inflammatory responses is critical for the clinical management of children with ARDS.",2017 Nov 13,"['Phung, Thuy Thi Bich', 'Suzuki, Tadaki', 'Phan, Phuc Huu', 'Kawachi, Shoji', 'Furuya, Hiroyuki', 'Do, Huong Thu', 'Kageyama, Tsutomu', 'Ta, Tuan Anh', 'Dao, Nam Huu', 'Nunoi, Hiroyuki', 'Tran, Dien Minh', 'Le, Hai Thanh', 'Nakajima, Noriko']",Pediatr Pulmonol,,,True
404f219ad630336f512bb52d5e6b357adf10e130,PMC,Urinary YKL-40 as a Candidate Biomarker for Febrile Urinary Tract Infection in Young Children,http://dx.doi.org/10.3343/alm.2018.38.1.39,PMC5700145,29071817,CC BY-NC,"BACKGROUND: Given that YKL-40 is a known marker of inflammation, we sought to determine its association with urinary tract infection (UTI) in febrile children. METHODS: In total, 44 children aged 0 to 24 months with febrile UTI and 35 age- and sex-matched controls with fever from other causes were enrolled in the study. ELISA was performed to determine the level of YKL-40 in urine collected from each child. RESULTS: The ratio of urinary YKL-40 to creatinine (Cr) was higher in the children with a UTI than in the controls (P<0.001). The area under the ROC curve for detecting UTI was 0.88 for the urinary YKL-40/Cr ratio, 0.86 for pyuria, and 0.71 for positive nitrite on urinalysis. We applied a cut-off value of 125.23 pg/mg to urinary YKL-40/Cr for detecting UTI. Eight of nine children in the control group with pyuria had urinary YKL-40/Cr levels lower than 125.23 pg/mg, and the one child in the UTI group without pyuria or positive nitrite had a urinary YKL-40/Cr level greater than 125.23 pg/mg. CONCLUSIONS: Determining the levels of urinary YKL-40/Cr may help identify true cases of UTI in febrile young children, especially when they have pyuria but not nitrite, or have neither pyuria nor nitrite in the urine.",2018 Jan 23,"['Kim, Hyun Hee', 'Chung, Mi Hae', 'Bin, Joong Hyun', 'Cho, Kyoung Soon', 'Lee, Juyoung', 'Suh, Jin-Soon']",Ann Lab Med,,,True
8f810a6f1464d6871d6184e04cf3fb1417983abc,PMC,Evaluation of Allplex Respiratory Panel 1/2/3 Multiplex Real-Time PCR Assays for the Detection of Respiratory Viruses with Influenza A Virus subtyping,http://dx.doi.org/10.3343/alm.2018.38.1.46,PMC5700146,29071818,CC BY-NC,"The Allplex Respiratory Panel 1/2/3 (All16) is a multiplex PCR assay for detecting 16 respiratory viruses with influenza A virus (FluA) subtyping, and the first clinical assay based on multiple detection temperatures. We compared the results between All16 and Anyplex II RV16 (Any16) in 426 clinical samples. Samples showing discrepancies between the two tests were further tested using monoplex PCR. FluA subtyping based on the hemagglutinin type results of All16, which yielded H1, H3, and non-H1/H3, was compared with the results of the BioFire FilmArray respiratory panel. The positive and negative percent agreements and kappa value for each virus between All16 and Any16 ranged from 54.5-100.0%, 84.7-100.0%, and 0.57-1.00, respectively. FluA subtype results from All16 for 26 samples were consistent with those from FilmArray. Good agreement was observed between the two methods, except when analyzing human enterovirus (kappa value 0.70), and the All16 showed reliable FluA subtyping results. For parainfluenza virus 3, the All16 was more sensitive than Any16. When testing 28 samples simultaneously, the mean test time and hands-on time were 4.3 and 0.5 hours, respectively in All16. In conclusion, All16 showed reliable performance, but further studies are needed regarding human enterovirus analysis.",2018 Jan 23,"['Lee, Jaehyeon', 'Lee, Hye Soo', 'Cho, Yong Gon', 'Choi, Sam Im', 'Kim, Dal Sik']",Ann Lab Med,,,True
996f46ba8e5ce3420f47a75b12cc4890240bc896,PMC,Evaluation of Allplex Respiratory Panel 1/2/3 Multiplex Real-Time PCR Assays for the Detection of Respiratory Viruses with Influenza A Virus subtyping,http://dx.doi.org/10.3343/alm.2018.38.1.46,PMC5700146,29071818,CC BY-NC,"The Allplex Respiratory Panel 1/2/3 (All16) is a multiplex PCR assay for detecting 16 respiratory viruses with influenza A virus (FluA) subtyping, and the first clinical assay based on multiple detection temperatures. We compared the results between All16 and Anyplex II RV16 (Any16) in 426 clinical samples. Samples showing discrepancies between the two tests were further tested using monoplex PCR. FluA subtyping based on the hemagglutinin type results of All16, which yielded H1, H3, and non-H1/H3, was compared with the results of the BioFire FilmArray respiratory panel. The positive and negative percent agreements and kappa value for each virus between All16 and Any16 ranged from 54.5-100.0%, 84.7-100.0%, and 0.57-1.00, respectively. FluA subtype results from All16 for 26 samples were consistent with those from FilmArray. Good agreement was observed between the two methods, except when analyzing human enterovirus (kappa value 0.70), and the All16 showed reliable FluA subtyping results. For parainfluenza virus 3, the All16 was more sensitive than Any16. When testing 28 samples simultaneously, the mean test time and hands-on time were 4.3 and 0.5 hours, respectively in All16. In conclusion, All16 showed reliable performance, but further studies are needed regarding human enterovirus analysis.",2018 Jan 23,"['Lee, Jaehyeon', 'Lee, Hye Soo', 'Cho, Yong Gon', 'Choi, Sam Im', 'Kim, Dal Sik']",Ann Lab Med,,,False
b05030dae8169323463be3fd847e447f48d4f902,PMC,Effects of patients’ motives in choosing a provider on determining the type of medical institution,http://dx.doi.org/10.2147/PPA.S148530,PMC5702172,29200834,CC BY-NC,"BACKGROUND: Primary care is relatively weak in the Republic of Korea. As the referral system is not well established, patients can freely choose from among clinics, hospitals, and tertiary hospitals. This study was conducted to determine the factors influencing patients’ choice of providers. METHODS: A survey was conducted of 999 Korean adults aged 19–59 years. An exploratory factor analysis was performed on nine factors influencing their motives in choosing a medical provider. The factors derived from this analysis and the types of medical institutions were used as the independent and dependent variables, respectively, in logistic regression analysis. Adjustments were made for region, gender, age, educational level, income, type of insurance, and chronic diseases. RESULTS: The results showed that patients preferred clinics when considering the importance of accessibility, staff kindness, and patient-centeredness; they preferred hospitals when considering cleanliness; and tertiary hospitals when considering the reputation and structural factors. When considering structural factors, clinics and hospitals were less preferred; however tertiary hospitals were less preferred when considering accessibility, staff kindness, and patient-centeredness. CONCLUSION: It is necessary to provide more accessible and patient-centered services in order to strengthen the primary health care role of clinics. In addition, efforts are needed to improve the quality of health care of tertiary hospitals in order to meet patient expectations.",2017 Nov 22,"['Kim, Yeon-Yong', 'Bae, Jaekyoung', 'Lee, Jin-Seok']",Patient Prefer Adherence,,,True
c8b0ef630df7327adda9757e8cca4aaac3fe69b3,PMC,Current Progress of Virus-mimicking Nanocarriers for Drug Delivery,http://dx.doi.org/10.7150/ntno.21723,PMC5704007,29188175,CC BY-NC,"Nanomedicines often involve the use of nanocarriers as a delivery system for drugs or genes for maximizing the therapeutic effect and/or minimizing the adverse effect. From drug administration to therapeutic activity, nanocarriers must evade the host's immune system, specifically and efficiently target and enter the cell, and release their payload into the cell cytoplasm by endosomal escape. These processes constitute the early infection stage of viruses. Viruses are a powerful natural nanomaterial for the efficient delivery of genetic information by sophisticated mechanisms. Over the past two decades, many virus-inspired nanocarriers have been generated to permit successful drug and gene delivery. In this review, we summarize the early infection machineries of viruses, of which the part has so far been utilized for delivery systems. Furthermore, we describe basics and applications of the bio-nanocapsule, which is a hepatitis B virus-mimicking nanoparticle harboring nearly all activities involved in the early infection machineries (i.e., stealth activity, targeting activity, cell entry activity, endosomal escaping activity).",2017 Oct 31,"['Somiya, Masaharu', 'Liu, Qiushi', ""Kuroda, Shun'ichi""]",Nanotheranostics,,,True
61c74b574c1b33ece0ca2f53861597d70c61a720,PMC,Ebola Preparedness in the Netherlands: The Need for Coordination Between the Public Health and the Curative Sector,http://dx.doi.org/10.1097/PHH.0000000000000573,PMC5704660,28353483,CC BY-NC-ND,"CONTEXT: During the Ebola outbreak in West Africa in 2014-2015, close cooperation between the curative sector and the public health sector in the Netherlands was necessary for timely identification, referral, and investigation of patients with suspected Ebola virus disease (EVD). OBJECTIVE: In this study, we evaluated experiences in preparedness among stakeholders of both curative and public health sectors to formulate recommendations for optimizing preparedness protocols. Timeliness of referred patients with suspected EVD was used as indicator for preparedness. DESIGN: In focus group sessions and semistructured interviews, experiences of curative and public health stakeholders about the regional and national process of preparedness and response were listed. Timeliness recordings of all referred patients with suspected EVD (13) were collected from first date of illness until arrival in the referral academic hospital. RESULTS: Ebola preparedness was considered extensive compared with the risk of an actual patient, however necessary. Regional coordination varied between regions. More standardization of regional preparation and operational guidelines was requested, as well as nationally standardized contingency criteria, and the National Centre for Infectious Disease Control was expected to coordinate the development of these guidelines. For the timeliness of referred patients with suspected EVD, the median delay between first date of illness until triage was 2.0 days (range: 0-10 days), and between triage and arrival in the referral hospital, it was 5.0 hours (range: 2-7.5 hours). In none of these patients Ebola infection was confirmed. CONCLUSIONS: Coordination between the public health sector and the curative sector needs improvement to reduce delay in patient management in emerging infectious diseases. Standardization of preparedness and response practices, through guidelines for institutional preparedness and blueprints for regional and national coordination, is necessary, as preparedness for emerging infectious diseases needs a multidisciplinary approach overarching both the public health sector and the curative sector. In the Netherlands a national platform for preparedness is established, in which both the curative sector and public health sector participate, in order to implement the outcomes of this study.",2018 Jan 22,"['Swaan, Corien M.', 'Öry, Alexander V.', 'Schol, Lianne G. C.', 'Jacobi, André', 'Richardus, Jan Hendrik', 'Timen, Aura']",J Public Health Manag Pract,,,True
c1909700d68a75f5d5390928295e7a4949c4cc41,PMC,An unusual cause of fever of unknown origin with enlarged lymph nodes—relapsing polychondritis: A case report,http://dx.doi.org/10.1097/MD.0000000000008734,PMC5704863,29145318,CC BY-NC-SA,"INTRODUCTION: Fever of unknown origin (FUO) is a common initial presentation leading to a diagnostic challenge. PATIENT CONCERNS: A 3-month history of moderate-to-high fever was reported in an otherwise healthy 54-year-old man. Enhanced computed tomography (CT) scans of his chest showed a remarkable progressive enlargement of bilateral cervical, supraclavicular, hilar, and mediastinal lymph nodes within 2 weeks. Bronchofibroscopy manifested obvious luminal stenosis with swelling, thick pale mucosa, and disappearing of structures of trachea cricoid cartilage, followed by a 18F-fluorodeoxyglucose positron-emission tomography–computed tomography (18F-FDG PET/CT) with intense symmetric FDG uptake in larynx, tracheobronchial tree, and hilar, mediastinal, and axillary lymph nodes being demonstrated. DIAGNOSIS: A diagnosis of relapsing polychondritis (RP) was finally reached. INTERVENTIONS: The patient received methylprednisolone 40 mg daily with a gradual tapering in a 4-month follow-up. OUTCOMES: The patient experienced no relapse of fever and lymph nodes enlargement in the 4-month follow-up. LESSONS: Even though long-term fever with multiple lymphadenectasis usually lead to a diagnosis of lymphoma, the bronchoscopic features and evidence from 18F-FDG PET/CT in this case were much more approximate to RP, indicating an importance of a sensible differential diagnosis of RP in patients who present with nonspecific features such as FUO and lymph nodes enlargement. Keeping a high index of clinical suspicion in these patients can help recognize uncommon of RP and promote diagnosis and treatment. Our case highlights the significance of 18F-FDG PET/CT in helping reaching the diagnosis of RP in this condition. This report provides new data regarding the diagnostic difficulties of this rare type of autoimmune disease, and further investigations are needed as cases accumulate.",2017 Nov 17,"['Liu, Wei', 'Jiang, Hongli', 'Jing, Han', 'Mao, Bing']",Medicine (Baltimore),,,True
b6b49bfba83105940015b7b8280db74ce480c65c,PMC,Viral Infections and Associated Factors That Promote Acute Exacerbations of Asthma,http://dx.doi.org/10.4168/aair.2018.10.1.12,PMC5705478,29178673,CC BY-NC,"Despite asthma being the most common chronic childhood ailment, there is still much to learn about the disease. Early childhood infections with well-known or emerging viruses can lay the pathophysiologic framework for asthma development and exacerbation later in life, which may be due partly to alteration of the airway microbiome. Once asthma is established, acute exacerbations are usually associated with infections with respiratory viruses, such as rhinoviruses (RVs). Once again, there are bidirectional interactions between viruses and airway bacteria that appear to influence the severity of illness and the likelihood of exacerbation. Studies employing recent advances in viral and bacterial identification analytic techniques will clarify these new concepts and may provide the basis for new treatments or prevention or respiratory infection-associated exacerbation. This paper is a review of the associations among respiratory viruses, bacteria, inflammatory mechanisms, and asthma exacerbation.",2018 Jan 13,"['Kim, Chang-Keun', 'Callaway, Zak', 'Gern, James E.']",Allergy Asthma Immunol Res,,,True
dca3423350c6278fe7b9479eb894a578ffeeeb68,PMC,Peptides as Therapeutic Agents for Dengue Virus,http://dx.doi.org/10.7150/ijms.21875,PMC5707751,29200948,CC BY-NC,"Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients.",2017 Oct 15,"['Chew, Miaw-Fang', 'Poh, Keat-Seong', 'Poh, Chit-Laa']",Int J Med Sci,,,True
84f8946f903a07243c54bde0a3e6d5ccecf9c5b9,PMC,Antibody response to equine coronavirus in horses inoculated with a bovine coronavirus vaccine,http://dx.doi.org/10.1292/jvms.17-0414,PMC5709570,28993568,CC BY-NC-ND,"A vaccine for equine coronavirus (ECoV) is so far unavailable. Bovine coronavirus (BCoV) is antigenically related to ECoV; it is therefore possible that BCoV vaccine will induce antibodies against ECoV in horses. This study investigated antibody response to ECoV in horses inoculated with BCoV vaccine. Virus neutralization tests showed that antibody titers against ECoV increased in all six horses tested at 14 days post inoculation, although the antibody titers were lower against ECoV than against BCoV. This study showed that BCoV vaccine provides horses with antibodies against ECoV to some extent. It is unclear whether antibodies provided by BCoV vaccine are effective against ECoV, and therefore ECoV challenge studies are needed to evaluate efficacy of the vaccine in the future.",2017 Nov 6,"['NEMOTO, Manabu', 'KANNO, Toru', 'BANNAI, Hiroshi', 'TSUJIMURA, Koji', 'YAMANAKA, Takashi', 'KOKADO, Hiroshi']",J Vet Med Sci,,,True
08079db5747d09016612f319e154ff81c4d9aef5,PMC,Porcine alveolar macrophage polarization is involved in inhibition of porcine reproductive and respiratory syndrome virus (PRRSV) replication,http://dx.doi.org/10.1292/jvms.17-0258,PMC5709573,28924090,CC BY-NC-ND,"Macrophage polarization is a process by which macrophages acquire a distinct phenotypic and functional profile in response to microenvironmental signals. The classically and alternatively activated (M1 and M2, respectively) macrophage phenotypes are defined by the specific molecular characteristics induced in response to prototypic pro- and anti-inflammatory cues. In this study, we used LPS/IFN-γ and IL-4 to stimulate porcine alveolar macrophages (PAMs) in vitro and investigated the expression changes of several novel markers during macrophage polarization. Notably, we found that LPS/IFN-γ-stimulated PAMs express prototypical M1 molecules, whereas IL-4-stimulated PAMs express M2 molecules. We also demonstrated that replication of the highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) strain HuN4 was effectively suppressed in LPS/IFN-γ-stimulated M1 PAMs (M1 type), but not IL-4 stimulated M2 PAMs. However, this was not observed with the classic, less pathogenic CH-1a strain. Moreover, we found that M2 marker expression gradually increased after PAM infection with PRRSV, whereas no significant changes were found with M1 marker expression, suggesting that PRRSV infection may skew macrophage polarization towards an M2 phenotype. Finally, we found that anti-viral cytokine expression was significantly higher in M1 macrophages than in M2 macrophages or nonpolarized controls. In summary, our results show that PRRSV replication was significantly impaired in M1 PAMs, which may serve as a foundation for further understanding of the dynamic phenotypic changes during macrophage polarization and their effects on viral infection.",2017 Nov 17,"['WANG, Longtao', 'HU, Shouping', 'LIU, Qiang', 'LI, Yiru', 'XU, Lu', 'ZHANG, Zhuo', 'CAI, Xuehui', 'HE, Xijun']",J Vet Med Sci,,,True
0d3de075e16c6d2e02c68e541b4d2654c78bea04,PMC,Bilateral pulmonary nodules and acute respiratory failure in a 22-year-old man with dyspnoea and fever,http://dx.doi.org/10.1183/20734735.008317,PMC5709794,29209425,CC BY-NC,Can you diagnose the cause of this man’s bilateral pulmonary nodules and acute respiratory failure? http://ow.ly/NfED30dDBzm,2017 Dec,"['Castellana, Giorgio', 'Liotino, Vito', 'Vulpi, Maria Rosaria', 'Ali, Ina', 'Marra, Lorenzo', 'Resta, Onofrio']",Breathe (Sheff),,,True
e735e236eed867ac5bb27abb3089f7cf9bde28f1,PMC,The Effect of Having a Regular Doctor as a Primary Care Provider on Emergency Room Utilization in South Korea,http://dx.doi.org/10.4082/kjfm.2017.38.6.322,PMC5711649,29209470,CC BY-NC,"BACKGROUND: Because primary care is the cornerstone of an effective health care system, many developed countries have striven to establish and strengthen their primary care systems. However, the primary care system in South Korea is not well established, and primary care research is still in its infancy. This study aimed to show the benefits of regular doctors as primary care providers in South Korea by analyzing the effect of regular doctor visits on emergency room (ER) visits. METHODS: We analyzed cross-sectional data on 11,293 adults aged 18 years and over collected from the 2013 Korea Health Panel Survey (beta version 1.0). We classified those participants with and without regular doctors into the treatment and control groups, respectively, and estimated the average treatment effect (ATE) of having a regular doctor on ER visits. We used counterfactual framework and propensity score analysis to adjust for unevenly distributed confounding covariates between treatments and control groups. RESULTS: The estimated conditional ATE of a regular doctor on ER visits was statistically insignificant in the general population (-0.4%; 95% confidence interval [CI], -2.0 to 1.2) and in the subgroup of patients with hypertension (-1.8%; 95% CI, -4.5 to 0.9). However, in patients with diabetes mellitus (DM), the estimated ATE was statistically significant (-5.0; 95% CI, -9.2 to -0.7). CONCLUSION: In the total study population, having a regular doctor did not result in a significant difference in ER visits. However, there was a decrease in ER visits in patients with DM in South Korea.",2017 Nov 14,"['Lee, Su-Young', 'Lim, Hyeong-Seok']",Korean J Fam Med,,,True
3b19c08ee471af50e75d3d2071699e88990cbe68,PMC,Prolonged Detection of Japanese Encephalitis Virus in Urine and Whole Blood in a Returned Short-term Traveler,http://dx.doi.org/10.1093/ofid/ofx203,PMC5714136,29226169,CC BY-NC-ND,"We describe a fatal case of Japanese encephalitis virus infection following short-term travel to Thailand. Viral RNA was detected in urine and whole blood out to 26 and 28 days, respectively, after the onset of symptoms. Live virus was isolated from a urine specimen from day 14.",2017 Sep 27,"['Huang, G Khai Lin', 'Tio, Shio Yen', 'Caly, Leon', 'Nicholson, Suellen', 'Thevarajan, Irani', 'Papadakis, Georgina', 'Catton, Mike', 'Tong, Steven Y C', 'Druce, Julian']",Open Forum Infect Dis,,,True
014e31dce7e3f2b1a7020a5debfbf228182f8b5e,PMC,Performance of materials used for biological personal protective equipment against blood splash penetration,http://dx.doi.org/10.2486/indhealth.2017-0120,PMC5718772,28978815,CC BY-NC-ND,"For occupational safety, healthcare workers must select and wear appropriate personal protective equipment (PPE), protective clothing, and masks as countermeasures against exposure to infectious body fluids and blood splash. It is important for healthcare workers to ensure the protective performance of each PPE against penetration of pathogens. The International Standards Organization (ISO) 22609 test evaluates the effectiveness of medical facemasks to protect against penetration of splashed synthetic blood. However, in this method, the protective performance is determined only visually, without quantification of leaked liquid volume. Therefore, in this study, we modified the ISO 22609 test method to quantify the volume of leaked liquid and obtain a more accurate assessment of the protection performance. We tested non-woven and woven materials used for masks or protective clothing, and the performance of each material was classified using this new method. We found that the quantity of leaked synthetic blood was dependent on the structural characteristics of each material. These findings will allow healthcare workers to select the most appropriate PPE for a given situation or task.",2017 Nov 5,"['SHIMASAKI, Noriko', 'SHINOHARA, Katsuaki', 'MORIKAWA, Hideki']",Ind Health,,,True
15f99a27eec125edd5f2c431344f01883ff72129,PMC,Vaccines for emerging infectious diseases: Lessons from MERS coronavirus and Zika virus,http://dx.doi.org/10.1080/21645515.2017.1358325,PMC5718785,28846484,CC BY-NC-ND,"The past decade and a half has been characterized by numerous emerging infectious diseases. With each new threat, there has been a call for rapid vaccine development. Pathogens such as the Middle East Respiratory Syndrome coronavirus (MERS-CoV) and the Zika virus represent either new viral entities or viruses emergent in new geographic locales and characterized by novel complications. Both serve as paradigms for the global spread that can accompany new pathogens. In this paper, we review the epidemiology and pathogenesis of MERS-CoV and Zika virus with respect to vaccine development. The challenges in vaccine development and the approach to clinical trial design to test vaccine candidates for disease entities with a changing epidemiology are discussed.",2017 Aug 28,"Maslow, Joel N.",Hum Vaccin Immunother,,,True
d1b24d21f2004ee1ed983d5fd7526ff2809443e6,PMC,Plant-made vaccines and reagents for the One Health initiative,http://dx.doi.org/10.1080/21645515.2017.1356497,PMC5718809,28846485,CC BY-NC-ND,"The One Health initiative is increasingly becoming a prominent discussion topic in animal and human health, with its focus on prevention of spread of zoonotic diseases, both in animals, and from animals to humans. An important part of One Health is that diagnostics and vaccines for diseases may be the same thing – and be used for both humans and animals. One potential problem standing in the way of wider adoption of One Health principles, though, is that use of conventional cell fermentation systems for production of the recombinant proteins that could be used as diagnostics or vaccines is often expensive and is not easily scalable. A solution to this may be the use of plants or plant cells as bioreactors: molecular farming, or the production of biologics in plants, is now a well-established science with many proofs of principle and important proofs of efficacy for especially animal vaccines. This review discusses how molecular farming could enable important advances in One Health, using as examples plant-made vacccines, reagents and therapeutics for influenza viruses, ebolaviruses, rabies virus, bunyaviruses and flaviviruses.",2017 Aug 28,"Rybicki, Edward Peter",Hum Vaccin Immunother,,,True
6d04e85d2c994d73c9a7e2692af91470f407ddeb,PMC,"Advancements in DNA vaccine vectors, non-mechanical delivery methods, and molecular adjuvants to increase immunogenicity",http://dx.doi.org/10.1080/21645515.2017.1330236,PMC5718814,28604157,CC BY-NC-ND,"A major advantage of DNA vaccination is the ability to induce both humoral and cellular immune responses. DNA vaccines are currently used in veterinary medicine, but have not achieved widespread acceptance for use in humans due to their low immunogenicity in early clinical studies. However, recent clinical data have re-established the value of DNA vaccines, particularly in priming high-level antigen-specific antibody responses. Several approaches have been investigated for improving DNA vaccine efficacy, including advancements in DNA vaccine vector design, the inclusion of genetically engineered cytokine adjuvants, and novel non-mechanical delivery methods. These strategies have shown promise, resulting in augmented adaptive immune responses in not only mice, but also in large animal models. Here, we review advancements in each of these areas that show promise for increasing the immunogenicity of DNA vaccines.",2017 Jun 12,"['Suschak, John J.', 'Williams, James A.', 'Schmaljohn, Connie S.']",Hum Vaccin Immunother,,,True
562e3acb22b8ed4cf3edec403ade2e3e425af531,PMC,A global perspective on hepatitis B‐related single nucleotide polymorphisms and evolution during human migration,http://dx.doi.org/10.1002/hep4.1113,PMC5721408,29404438,CC BY-NC-ND,"Genome‐wide association studies have indicated that human leukocyte antigen (HLA)‐DP and HLA‐DQ play roles in persistent hepatitis B virus (HBV) infection in Asia. To understand the evolution of HBV‐related single nucleotide polymorphisms (SNPs) and to correlate these SNPs with chronic HBV infection among different populations, we conducted a global perspective study on hepatitis‐related SNPs. We selected 12 HBV‐related SNPs on the HLA locus and two HBV and three hepatitis C virus immune‐related SNPs for analysis. Five nasopharyngeal carcinoma‐related SNPs served as controls. All SNP data worldwide from 26 populations were downloaded from 1,000 genomes. We found a dramatic difference in the allele frequency in most of the HBV‐ and HLA‐related SNPs in East Asia compared to the other continents. A sharp change in allele frequency in 8 of 12 SNPs was found between Bengali populations in Bangladesh and Chinese Dai populations in Xishuangbanna, China (P < 0.001); these areas represent the junction of South and East Asia. For the immune‐related SNPs, significant changes were found after leaving Africa. Most of these genes shifted from higher expression genotypes in Africa to lower expression genotypes in either Europe or South Asia (P < 0.001). During this two‐stage adaptation, immunity adjusted toward a weak immune response, which could have been a survival strategy during human migration to East Asia. The prevalence of chronic HBV infection in Africa is as high as in Asia; however, the HBV‐related SNP genotypes are not present in Africa, and so the genetic mechanism of chronic HBV infection in Africa needs further exploration. Conclusion: Two stages of genetic changes toward a weak immune response occurred when humans migrated out of Africa. These changes could be a survival strategy for avoiding cytokine storms and surviving in new environments. (Hepatology Communications 2017;1:1005–1013)",2017 Nov 6,"['Tai, Dar‐In', 'Jeng, Wen‐Juei', 'Lin, Chun‐Yen']",Hepatol Commun,,,True
d0571fb440ff2f4ce7014760267fb9f273311415,PMC,Multicentre randomised controlled trial to investigate the usefulness of continuous pneumatic regulation of tracheal cuff pressure for reducing ventilator-associated pneumonia in mechanically ventilated severe trauma patients: the AGATE study protocol,http://dx.doi.org/10.1136/bmjopen-2017-017003,PMC5724199,28790042,CC BY-NC,"INTRODUCTION: Severe trauma represents the leading cause of mortality worldwide. While 80% of deaths occur within the first 24 hours after trauma, 20% occur later and are mainly due to healthcare-associated infections, including ventilator-associated pneumonia (VAP). Preventing underinflation of the tracheal cuff is recommended to reduce microaspiration, which plays a major role in the pathogenesis of VAP. Automatic devices facilitate the regulation of tracheal cuff pressure, and their implementation has the potential to reduce VAP. The objective of this work is to determine whether continuous regulation of tracheal cuff pressure using a pneumatic device reduces the incidence of VAP compared with intermittent control in severe trauma patients. METHODS AND ANALYSIS: This multicentre randomised controlled and open-label trial will include patients suffering from severe trauma who are admitted within the first 24 hours, who require invasive mechanical ventilation to longer than 48 hours. Their tracheal cuff pressure will be monitored either once every 8 hours (control group) or continuously using a pneumatic device (intervention group). The primary end point is the proportion of patients that develop VAP in the intensive care unit (ICU) at day 28. The secondary end points include the proportion of patients that develop VAP in the ICU, early (≤7 days) or late (>7 days) VAP, time until the first VAP diagnosis, the number of ventilator-free days and antibiotic-free days, the length of stay in the ICU, the proportion of patients with ventilator-associated events and that die during their ICU stay. ETHICS AND DISSEMINATION: This protocol has been approved by the ethics committee of Poitiers University Hospital, and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. TRIAL REGISTRATION: Clinical Trials NCT02534974",2017 Aug 7,"['Marjanovic, Nicolas', 'Frasca, Denis', 'Asehnoune, Karim', 'Paugam, Catherine', 'Lasocki, Sigismond', 'Ichai, Carole', 'Lefrant, Jean-Yves', 'Leone, Marc', 'Dahyot-Fizelier, Claire', 'Pottecher, Julien', 'Falcon, Dominique', 'Veber, Benoit', 'Constantin, Jean-Michel', 'Seguin, Sabrina', 'Guénézan, Jérémy', 'Mimoz, Olivier']",BMJ Open,,,True
1369823dbf5f34fd8e2f5d5bba470711dfca4032,PMC,Multicentre randomised controlled trial to investigate the usefulness of continuous pneumatic regulation of tracheal cuff pressure for reducing ventilator-associated pneumonia in mechanically ventilated severe trauma patients: the AGATE study protocol,http://dx.doi.org/10.1136/bmjopen-2017-017003,PMC5724199,28790042,CC BY-NC,"INTRODUCTION: Severe trauma represents the leading cause of mortality worldwide. While 80% of deaths occur within the first 24 hours after trauma, 20% occur later and are mainly due to healthcare-associated infections, including ventilator-associated pneumonia (VAP). Preventing underinflation of the tracheal cuff is recommended to reduce microaspiration, which plays a major role in the pathogenesis of VAP. Automatic devices facilitate the regulation of tracheal cuff pressure, and their implementation has the potential to reduce VAP. The objective of this work is to determine whether continuous regulation of tracheal cuff pressure using a pneumatic device reduces the incidence of VAP compared with intermittent control in severe trauma patients. METHODS AND ANALYSIS: This multicentre randomised controlled and open-label trial will include patients suffering from severe trauma who are admitted within the first 24 hours, who require invasive mechanical ventilation to longer than 48 hours. Their tracheal cuff pressure will be monitored either once every 8 hours (control group) or continuously using a pneumatic device (intervention group). The primary end point is the proportion of patients that develop VAP in the intensive care unit (ICU) at day 28. The secondary end points include the proportion of patients that develop VAP in the ICU, early (≤7 days) or late (>7 days) VAP, time until the first VAP diagnosis, the number of ventilator-free days and antibiotic-free days, the length of stay in the ICU, the proportion of patients with ventilator-associated events and that die during their ICU stay. ETHICS AND DISSEMINATION: This protocol has been approved by the ethics committee of Poitiers University Hospital, and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. TRIAL REGISTRATION: Clinical Trials NCT02534974",2017 Aug 7,"['Marjanovic, Nicolas', 'Frasca, Denis', 'Asehnoune, Karim', 'Paugam, Catherine', 'Lasocki, Sigismond', 'Ichai, Carole', 'Lefrant, Jean-Yves', 'Leone, Marc', 'Dahyot-Fizelier, Claire', 'Pottecher, Julien', 'Falcon, Dominique', 'Veber, Benoit', 'Constantin, Jean-Michel', 'Seguin, Sabrina', 'Guénézan, Jérémy', 'Mimoz, Olivier']",BMJ Open,,,True
3abe88de0279ff42328c997c2d85eed615e3b76a,PMC,Multicentre randomised controlled trial to investigate the usefulness of continuous pneumatic regulation of tracheal cuff pressure for reducing ventilator-associated pneumonia in mechanically ventilated severe trauma patients: the AGATE study protocol,http://dx.doi.org/10.1136/bmjopen-2017-017003,PMC5724199,28790042,CC BY-NC,"INTRODUCTION: Severe trauma represents the leading cause of mortality worldwide. While 80% of deaths occur within the first 24 hours after trauma, 20% occur later and are mainly due to healthcare-associated infections, including ventilator-associated pneumonia (VAP). Preventing underinflation of the tracheal cuff is recommended to reduce microaspiration, which plays a major role in the pathogenesis of VAP. Automatic devices facilitate the regulation of tracheal cuff pressure, and their implementation has the potential to reduce VAP. The objective of this work is to determine whether continuous regulation of tracheal cuff pressure using a pneumatic device reduces the incidence of VAP compared with intermittent control in severe trauma patients. METHODS AND ANALYSIS: This multicentre randomised controlled and open-label trial will include patients suffering from severe trauma who are admitted within the first 24 hours, who require invasive mechanical ventilation to longer than 48 hours. Their tracheal cuff pressure will be monitored either once every 8 hours (control group) or continuously using a pneumatic device (intervention group). The primary end point is the proportion of patients that develop VAP in the intensive care unit (ICU) at day 28. The secondary end points include the proportion of patients that develop VAP in the ICU, early (≤7 days) or late (>7 days) VAP, time until the first VAP diagnosis, the number of ventilator-free days and antibiotic-free days, the length of stay in the ICU, the proportion of patients with ventilator-associated events and that die during their ICU stay. ETHICS AND DISSEMINATION: This protocol has been approved by the ethics committee of Poitiers University Hospital, and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. TRIAL REGISTRATION: Clinical Trials NCT02534974",2017 Aug 7,"['Marjanovic, Nicolas', 'Frasca, Denis', 'Asehnoune, Karim', 'Paugam, Catherine', 'Lasocki, Sigismond', 'Ichai, Carole', 'Lefrant, Jean-Yves', 'Leone, Marc', 'Dahyot-Fizelier, Claire', 'Pottecher, Julien', 'Falcon, Dominique', 'Veber, Benoit', 'Constantin, Jean-Michel', 'Seguin, Sabrina', 'Guénézan, Jérémy', 'Mimoz, Olivier']",BMJ Open,,,False
70549fd773d28dfe6e47cbc51775b61c1816003f,PMC,"Fitting dynamic models to epidemic outbreaks with quantified uncertainty: A primer for parameter uncertainty, identifiability, and forecasts",http://dx.doi.org/10.1016/j.idm.2017.08.001,PMC5726591,29250607,CC BY-NC-ND,"Mathematical models provide a quantitative framework with which scientists can assess hypotheses on the potential underlying mechanisms that explain patterns in observed data at different spatial and temporal scales, generate estimates of key kinetic parameters, assess the impact of interventions, optimize the impact of control strategies, and generate forecasts. We review and illustrate a simple data assimilation framework for calibrating mathematical models based on ordinary differential equation models using time series data describing the temporal progression of case counts relating, for instance, to population growth or infectious disease transmission dynamics. In contrast to Bayesian estimation approaches that always raise the question of how to set priors for the parameters, this frequentist approach relies on modeling the error structure in the data. We discuss issues related to parameter identifiability, uncertainty quantification and propagation as well as model performance and forecasts along examples based on phenomenological and mechanistic models parameterized using simulated and real datasets.",2017 Aug 12,"Chowell, Gerardo",Infect Dis Model,,,False
e95276ff8455b1bb0a87994f9db6ca3a9c884399,PMC,Risk factors for detection failures of chest radiography in diagnosing pneumonia,http://dx.doi.org/10.1002/jgf2.111,PMC5729325,29264071,CC BY-NC,"BACKGROUND: Little is known about clinical factors associated with undetectable pneumonic shadows on chest radiographs (CRs) for diagnosing pneumonia in the primary care setting. METHODS: A retrospective assessment of CRs was conducted to compare chest computed tomography (CT) images of patients admitted to Kesennuma City Motoyoshi Municipal Hospital who were diagnosed with pneumonia from April 2014 to June 2016. RESULTS: Eighty‐three patients were included, and their average age was 83.8 years. Sixty‐eight patients (81.9%) were officially certified as requiring long‐term care or support. Twenty‐nine of the 83 patients (34.9%) had either negative or normal findings on CRs, and positive findings consistent with pneumonia on CT. There were no significant differences in gender, age, cardiothoracic ratio on CR, or severity between the CR‐negative and CR‐positive groups. The proportion of negative CRs was significantly higher in patients with certified care level 5 under the long‐term care system in Japan and tube feeding. CONCLUSION: The failure rate of CRs for detecting pneumonic shadows was significantly higher in patients with certified care level 5 and tube feeding.",2017 Jun 21,"['Sugishita, Keiji', 'Saito, Toshiaki', 'Asayama, Yukino', 'Iwamoto, Takashi']",J Gen Fam Med,,,True
f9a3b2b8a17beb5d81c2111277d9645dc137dd32,PMC,Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome: Current Therapeutic Options and Potential Targets for Novel Therapies,http://dx.doi.org/10.1007/s40265-017-0830-1,PMC5733787,29143192,CC BY-NC,"No specific antivirals are currently available for two emerging infectious diseases, Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). A literature search covering pathogenesis, clinical features and therapeutics, clinically developed drugs for repurposing and novel drug targets was performed. This review presents current knowledge on the epidemiology, pathogenesis and clinical features of the SARS and MERS coronaviruses. The rationale for and outcomes with treatments used for SARS and MERS is discussed. The main focus of the review is on drug development and the potential that drugs approved for other indications provide for repurposing. The drugs we discuss belong to a wide range of different drug classes, such as cancer therapeutics, antipsychotics, and antimalarials. In addition to their activity against MERS and SARS coronaviruses, many of these approved drugs have broad-spectrum potential and have already been in clinical use for treating other viral infections. A wealth of knowledge is available for these drugs. However, the information in this review is not meant to guide clinical decisions, and any therapeutic described here should only be used in context of a clinical trial. Potential targets for novel antivirals and antibodies are discussed as well as lessons learned from treatment development for other RNA viruses. The article concludes with a discussion of the gaps in our knowledge and areas for future research on emerging coronaviruses.",2017 Dec,"['Dyall, Julie', 'Gross, Robin', 'Kindrachuk, Jason', 'Johnson, Reed F.', 'Olinger, Gene G.', 'Hensley, Lisa E.', 'Frieman, Matthew B.', 'Jahrling, Peter B.']",Drugs,,,True
638c624925ed19a692dcd98a7285191537b1c7c0,PMC,Prospective observational study in two Dutch hospitals to assess the performance of inflammatory plasma markers to determine disease severity of viral respiratory tract infections in children,http://dx.doi.org/10.1136/bmjopen-2016-014596,PMC5734420,28667205,CC BY-NC,"INTRODUCTION: Respiratory viruses causing lower respiratory tract infections (LRTIs) are a major cause of hospital admissions in children. Since the course of these infections is unpredictable with potential fast deterioration into respiratory failure, infants are easily admitted to the hospital for observation. The aim of this study was to examine whether systemic inflammatory markers can be used to predict severity of disease in children with respiratory viral infections. METHODS: Blood and nasopharyngeal washings from children <3 years of age with viral LRTI attending a hospital were collected within 24 hours (acute) and after 4–6 weeks (recovery). Patients were assigned to a mild (observation only), moderate (supplemental oxygen and/or nasogastric feeding) or severe (mechanical ventilation) group. Linear regression analysis was used to design a prediction rule using plasma levels of C reactive protein (CRP), serum amyloid A (SAA), pentraxin 3 (PTX3), serum amyloid P component and properdin. This rule was tested in a validation cohort. RESULTS: One hundred and four children (52% male) were included. A combination of CRP, SAA, PTX3 and properdin was a better indicator of severe disease compared with any of the individual makers and age (69% sensitivity (95% CI 50 to 83), 90% specificity (95% CI 80 to 96)). Validation in 141 patients resulted in 71% sensitivity (95% CI 53 to 85), 87% specificity (95% CI 79 to 92), negative predictive value of 64% (95% CI 47 to 78) and positive predictive value of 90% (95% CI 82 to 95). The prediction rule was not able to identify patients with a mild course of disease. CONCLUSION: A combination of CRP, SAA, PTX3 and properdin was able to identify children with a severe course of viral LRTI disease, even in children under 2 months of age. To assess the true impact on clinical management, these results should be validated in a prospective randomised control study.",2017 Jun 30,"['Ahout, Inge M L', 'Brand, Kim H', 'Zomer, Aldert', 'van den Hurk, Wilhelma H', 'Schilders, Geurt', 'Brouwer, Marianne L', 'Neeleman, Chris', 'de Groot, Ronald', 'Ferwerda, Gerben']",BMJ Open,,,True
ca46502bc5b38f9453f31a3f34ba1711e98d83a9,PMC,Prospective observational study in two Dutch hospitals to assess the performance of inflammatory plasma markers to determine disease severity of viral respiratory tract infections in children,http://dx.doi.org/10.1136/bmjopen-2016-014596,PMC5734420,28667205,CC BY-NC,"INTRODUCTION: Respiratory viruses causing lower respiratory tract infections (LRTIs) are a major cause of hospital admissions in children. Since the course of these infections is unpredictable with potential fast deterioration into respiratory failure, infants are easily admitted to the hospital for observation. The aim of this study was to examine whether systemic inflammatory markers can be used to predict severity of disease in children with respiratory viral infections. METHODS: Blood and nasopharyngeal washings from children <3 years of age with viral LRTI attending a hospital were collected within 24 hours (acute) and after 4–6 weeks (recovery). Patients were assigned to a mild (observation only), moderate (supplemental oxygen and/or nasogastric feeding) or severe (mechanical ventilation) group. Linear regression analysis was used to design a prediction rule using plasma levels of C reactive protein (CRP), serum amyloid A (SAA), pentraxin 3 (PTX3), serum amyloid P component and properdin. This rule was tested in a validation cohort. RESULTS: One hundred and four children (52% male) were included. A combination of CRP, SAA, PTX3 and properdin was a better indicator of severe disease compared with any of the individual makers and age (69% sensitivity (95% CI 50 to 83), 90% specificity (95% CI 80 to 96)). Validation in 141 patients resulted in 71% sensitivity (95% CI 53 to 85), 87% specificity (95% CI 79 to 92), negative predictive value of 64% (95% CI 47 to 78) and positive predictive value of 90% (95% CI 82 to 95). The prediction rule was not able to identify patients with a mild course of disease. CONCLUSION: A combination of CRP, SAA, PTX3 and properdin was able to identify children with a severe course of viral LRTI disease, even in children under 2 months of age. To assess the true impact on clinical management, these results should be validated in a prospective randomised control study.",2017 Jun 30,"['Ahout, Inge M L', 'Brand, Kim H', 'Zomer, Aldert', 'van den Hurk, Wilhelma H', 'Schilders, Geurt', 'Brouwer, Marianne L', 'Neeleman, Chris', 'de Groot, Ronald', 'Ferwerda, Gerben']",BMJ Open,,,True
9f9954a88019077bffc1c2efcbab97f0f0a466b4,PMC,Prospective observational study in two Dutch hospitals to assess the performance of inflammatory plasma markers to determine disease severity of viral respiratory tract infections in children,http://dx.doi.org/10.1136/bmjopen-2016-014596,PMC5734420,28667205,CC BY-NC,"INTRODUCTION: Respiratory viruses causing lower respiratory tract infections (LRTIs) are a major cause of hospital admissions in children. Since the course of these infections is unpredictable with potential fast deterioration into respiratory failure, infants are easily admitted to the hospital for observation. The aim of this study was to examine whether systemic inflammatory markers can be used to predict severity of disease in children with respiratory viral infections. METHODS: Blood and nasopharyngeal washings from children <3 years of age with viral LRTI attending a hospital were collected within 24 hours (acute) and after 4–6 weeks (recovery). Patients were assigned to a mild (observation only), moderate (supplemental oxygen and/or nasogastric feeding) or severe (mechanical ventilation) group. Linear regression analysis was used to design a prediction rule using plasma levels of C reactive protein (CRP), serum amyloid A (SAA), pentraxin 3 (PTX3), serum amyloid P component and properdin. This rule was tested in a validation cohort. RESULTS: One hundred and four children (52% male) were included. A combination of CRP, SAA, PTX3 and properdin was a better indicator of severe disease compared with any of the individual makers and age (69% sensitivity (95% CI 50 to 83), 90% specificity (95% CI 80 to 96)). Validation in 141 patients resulted in 71% sensitivity (95% CI 53 to 85), 87% specificity (95% CI 79 to 92), negative predictive value of 64% (95% CI 47 to 78) and positive predictive value of 90% (95% CI 82 to 95). The prediction rule was not able to identify patients with a mild course of disease. CONCLUSION: A combination of CRP, SAA, PTX3 and properdin was able to identify children with a severe course of viral LRTI disease, even in children under 2 months of age. To assess the true impact on clinical management, these results should be validated in a prospective randomised control study.",2017 Jun 30,"['Ahout, Inge M L', 'Brand, Kim H', 'Zomer, Aldert', 'van den Hurk, Wilhelma H', 'Schilders, Geurt', 'Brouwer, Marianne L', 'Neeleman, Chris', 'de Groot, Ronald', 'Ferwerda, Gerben']",BMJ Open,,,False
61fa24457c8079a1d4668f0929804983f1ee8197,PMC,Prospective observational study in two Dutch hospitals to assess the performance of inflammatory plasma markers to determine disease severity of viral respiratory tract infections in children,http://dx.doi.org/10.1136/bmjopen-2016-014596,PMC5734420,28667205,CC BY-NC,"INTRODUCTION: Respiratory viruses causing lower respiratory tract infections (LRTIs) are a major cause of hospital admissions in children. Since the course of these infections is unpredictable with potential fast deterioration into respiratory failure, infants are easily admitted to the hospital for observation. The aim of this study was to examine whether systemic inflammatory markers can be used to predict severity of disease in children with respiratory viral infections. METHODS: Blood and nasopharyngeal washings from children <3 years of age with viral LRTI attending a hospital were collected within 24 hours (acute) and after 4–6 weeks (recovery). Patients were assigned to a mild (observation only), moderate (supplemental oxygen and/or nasogastric feeding) or severe (mechanical ventilation) group. Linear regression analysis was used to design a prediction rule using plasma levels of C reactive protein (CRP), serum amyloid A (SAA), pentraxin 3 (PTX3), serum amyloid P component and properdin. This rule was tested in a validation cohort. RESULTS: One hundred and four children (52% male) were included. A combination of CRP, SAA, PTX3 and properdin was a better indicator of severe disease compared with any of the individual makers and age (69% sensitivity (95% CI 50 to 83), 90% specificity (95% CI 80 to 96)). Validation in 141 patients resulted in 71% sensitivity (95% CI 53 to 85), 87% specificity (95% CI 79 to 92), negative predictive value of 64% (95% CI 47 to 78) and positive predictive value of 90% (95% CI 82 to 95). The prediction rule was not able to identify patients with a mild course of disease. CONCLUSION: A combination of CRP, SAA, PTX3 and properdin was able to identify children with a severe course of viral LRTI disease, even in children under 2 months of age. To assess the true impact on clinical management, these results should be validated in a prospective randomised control study.",2017 Jun 30,"['Ahout, Inge M L', 'Brand, Kim H', 'Zomer, Aldert', 'van den Hurk, Wilhelma H', 'Schilders, Geurt', 'Brouwer, Marianne L', 'Neeleman, Chris', 'de Groot, Ronald', 'Ferwerda, Gerben']",BMJ Open,,,False
84c2f00555536eb03aedc2225769f3b1ac59d94f,PMC,Evaluation of acute and sublethal effects of chloroquine (C(18)H(26)CIN(3)) on certain enzymological and histopathological biomarker responses of a freshwater fish Cyprinus carpio,http://dx.doi.org/10.1016/j.toxrep.2017.11.006,PMC5734797,29270363,CC BY-NC-ND,"In this study the toxicity of antimalarial drug chloroquine (CQ) on certain enzymological (GOT, GPT and LDH) and histopathological alterations (Gill, liver and kidney) of a freshwater fish Cyprinus carpio was studied after acute (96 h) and sublethal (35 days) exposure. The median lethal concentration (96 h) of CQ was 31.62 mg/ml. During acute treatment (CQ at 31.62 mg/ml) the treated fish groups showed a significant increase in GOT and GPT activities in blood plasma; whereas LDH activity was decreased when compare to control groups. To analyse the effects of drug at the lowest concentration, the fish were exposed to 3.16 mg/ml (1/10th of 96 h LC50 value) for 96 h. In sublethal treatment (3.16 mg/ml) GOT activity increased up to 14th day and decreased during the rest of the exposure period (21, 28 and 35th day). A biphasic response in GPT activity was observed. LDH activity was found to be increased throughout the study period (35 days) compare to control groups. The alterations in enzyme activities in blood plasma were found to be significant at p < 0.05 (DMRT). Many histopathological changes in vital organs such as gill, liver and kidney of fish were observed in CQ treated group (acute and sub-lethal) compare to normal group. The alterations in the enzymological and histopathological study in the present investigation indicate that the drug CQ has toxic effects on non-target organisms. We conclude that the alterations in enzymological parameters and histopathological changes can be used as biomarker to assess the health of the aquatic organism/environment. Further data on molecular studies are needed to define the mode of action and toxicity of these emerging pollutants.",2017 Dec 5,"['Ramesh, Mathan', 'Anitha, Selvaraj', 'Poopal, Rama Krishnan', 'Shobana, Chellappan']",Toxicol Rep,,,False
750eb3af6059e879b20beac9fb982f85332dd552,PMC,Evidence of translation efficiency adaptation of the coding regions of the bacteriophage lambda,http://dx.doi.org/10.1093/dnares/dsx005,PMC5737525,28338832,CC BY-NC,"Deciphering the way gene expression regulatory aspects are encoded in viral genomes is a challenging mission with ramifications related to all biomedical disciplines. Here, we aimed to understand how the evolution shapes the bacteriophage lambda genes by performing a high resolution analysis of ribosomal profiling data and gene expression related synonymous/silent information encoded in bacteriophage coding regions. We demonstrated evidence of selection for distinct compositions of synonymous codons in early and late viral genes related to the adaptation of translation efficiency to different bacteriophage developmental stages. Specifically, we showed that evolution of viral coding regions is driven, among others, by selection for codons with higher decoding rates; during the initial/progressive stages of infection the decoding rates in early/late genes were found to be superior to those in late/early genes, respectively. Moreover, we argued that selection for translation efficiency could be partially explained by adaptation to Escherichia coli tRNA pool and the fact that it can change during the bacteriophage life cycle. An analysis of additional aspects related to the expression of viral genes, such as mRNA folding and more complex/longer regulatory signals in the coding regions, is also reported. The reported conclusions are likely to be relevant also to additional viruses.",2017 Aug 28,"['Goz, Eli', 'Mioduser, Oriah', 'Diament, Alon', 'Tuller, Tamir']",DNA Res,,,True
ffed5d2a31a0c1a0db11905fe378e7735b6d70ca,PMC,Evidence of translation efficiency adaptation of the coding regions of the bacteriophage lambda,http://dx.doi.org/10.1093/dnares/dsx005,PMC5737525,28338832,CC BY-NC,"Deciphering the way gene expression regulatory aspects are encoded in viral genomes is a challenging mission with ramifications related to all biomedical disciplines. Here, we aimed to understand how the evolution shapes the bacteriophage lambda genes by performing a high resolution analysis of ribosomal profiling data and gene expression related synonymous/silent information encoded in bacteriophage coding regions. We demonstrated evidence of selection for distinct compositions of synonymous codons in early and late viral genes related to the adaptation of translation efficiency to different bacteriophage developmental stages. Specifically, we showed that evolution of viral coding regions is driven, among others, by selection for codons with higher decoding rates; during the initial/progressive stages of infection the decoding rates in early/late genes were found to be superior to those in late/early genes, respectively. Moreover, we argued that selection for translation efficiency could be partially explained by adaptation to Escherichia coli tRNA pool and the fact that it can change during the bacteriophage life cycle. An analysis of additional aspects related to the expression of viral genes, such as mRNA folding and more complex/longer regulatory signals in the coding regions, is also reported. The reported conclusions are likely to be relevant also to additional viruses.",2017 Aug 28,"['Goz, Eli', 'Mioduser, Oriah', 'Diament, Alon', 'Tuller, Tamir']",DNA Res,,,True
25aad84c22269cf7221d0c22737e2e01a36ec51b,PMC,"Stimulation of reverse transcriptase generated cDNAs with specific indels by template RNA structure: retrotransposon, dNTP balance, RT-reagent usage",http://dx.doi.org/10.1093/nar/gkx689,PMC5737552,28973469,CC BY-NC,"RNA dependent DNA-polymerases, reverse transcriptases, are key enzymes for retroviruses and retroelements. Their fidelity, including indel generation, is significant for their use as reagents including for deep sequencing. Here, we report that certain RNA template structures and G-rich sequences, ahead of diverse reverse transcriptases can be strong stimulators for slippage at slippage-prone template motif sequence 3′ of such ‘slippage-stimulatory’ structures. Where slippage is stimulated, the resulting products have one or more additional base(s) compared to the corresponding template motif. Such structures also inhibit slippage-mediated base omission which can be more frequent in the absence of a relevant stem–loop. Slippage directionality, base insertion and omission, is sensitive to the relative concentration ratio of dNTPs specified by the RNA template slippage-prone sequence and its 5′ adjacent base. The retrotransposon-derived enzyme TGIRT exhibits more slippage in vitro than the retroviral enzymes tested including that from HIV. Structure-mediated slippage may be exhibited by other polymerases and enrich gene expression. A cassette from Drosophila retrotransposon Dme1_chrX_2630566, a candidate for utilizing slippage for its GagPol synthesis, exhibits strong slippage in vitro. Given the widespread occurrence and importance of retrotransposons, systematic studies to reveal the extent of their functional utilization of RT slippage are merited.",2017 Sep 29,"['Penno, Christophe', 'Kumari, Romika', 'Baranov, Pavel V.', 'van\xa0Sinderen, Douwe', 'Atkins, John F.']",Nucleic Acids Res,,,True
c3e85c0632ee31d2327ceb70161066e29a02d499,PMC,Tidal changes on CT and progression of ARDS,http://dx.doi.org/10.1136/thoraxjnl-2016-209833,PMC5738538,28634220,CC BY-NC,"BACKGROUND: Uncertain prediction of outcome in acute respiratory distress syndrome (ARDS) impedes individual patient management and clinical trial design. OBJECTIVES: To develop a radiological metric of injurious inflation derived from matched inspiratory and expiratory CT scans, calibrate it in a model of experimental lung injury, and test it in patients with ARDS. METHODS: 73 anaesthetised rats (acid aspiration model) were ventilated (protective or non-protective) for up to 4 hours to generate a spectrum of lung injury. CT was performed (inspiratory and expiratory) at baseline each hour, paired inspiratory and expiratory images were superimposed and voxels tracked in sequential scans. In nine patients with ARDS, paired inspiratory and expiratory CT scans from the first intensive care unit week were analysed. RESULTS: In experimental studies, regions of lung with unstable inflation (ie, partial or reversible airspace filling reflecting local strain) were the areas in which subsequent progression of injury was greatest in terms of progressive infiltrates (R=0.77) and impaired compliance (R=0.67, p<0.01). In patients with ARDS, a threshold fraction of tissue with unstable inflation was apparent: >28% in all patients who died and ≤28% in all who survived, whereas segregation of survivors versus non-survivors was not possible based on oxygenation or lung mechanics. CONCLUSIONS: A single set of superimposed inspiratory–expiratory CT scans may predict progression of lung injury and outcome in ARDS; if these preliminary results are validated, this could facilitate clinical trial recruitment and individualised care.",2017 Nov 20,"['Cereda, Maurizio', 'Xin, Yi', 'Hamedani, Hooman', 'Bellani, Giacomo', 'Kadlecek, Stephen', 'Clapp, Justin', 'Guerra, Luca', 'Meeder, Natalie', 'Rajaei, Jennia', 'Tustison, Nicholas J', 'Gee, James C', 'Kavanagh, Brian P', 'Rizi, Rahim R']",Thorax,,,True
3c47eea51db8f16e9de1d4303cfe054cc39416cc,PMC,Tidal changes on CT and progression of ARDS,http://dx.doi.org/10.1136/thoraxjnl-2016-209833,PMC5738538,28634220,CC BY-NC,"BACKGROUND: Uncertain prediction of outcome in acute respiratory distress syndrome (ARDS) impedes individual patient management and clinical trial design. OBJECTIVES: To develop a radiological metric of injurious inflation derived from matched inspiratory and expiratory CT scans, calibrate it in a model of experimental lung injury, and test it in patients with ARDS. METHODS: 73 anaesthetised rats (acid aspiration model) were ventilated (protective or non-protective) for up to 4 hours to generate a spectrum of lung injury. CT was performed (inspiratory and expiratory) at baseline each hour, paired inspiratory and expiratory images were superimposed and voxels tracked in sequential scans. In nine patients with ARDS, paired inspiratory and expiratory CT scans from the first intensive care unit week were analysed. RESULTS: In experimental studies, regions of lung with unstable inflation (ie, partial or reversible airspace filling reflecting local strain) were the areas in which subsequent progression of injury was greatest in terms of progressive infiltrates (R=0.77) and impaired compliance (R=0.67, p<0.01). In patients with ARDS, a threshold fraction of tissue with unstable inflation was apparent: >28% in all patients who died and ≤28% in all who survived, whereas segregation of survivors versus non-survivors was not possible based on oxygenation or lung mechanics. CONCLUSIONS: A single set of superimposed inspiratory–expiratory CT scans may predict progression of lung injury and outcome in ARDS; if these preliminary results are validated, this could facilitate clinical trial recruitment and individualised care.",2017 Nov 20,"['Cereda, Maurizio', 'Xin, Yi', 'Hamedani, Hooman', 'Bellani, Giacomo', 'Kadlecek, Stephen', 'Clapp, Justin', 'Guerra, Luca', 'Meeder, Natalie', 'Rajaei, Jennia', 'Tustison, Nicholas J', 'Gee, James C', 'Kavanagh, Brian P', 'Rizi, Rahim R']",Thorax,,,True
54e82ae1126dc9eed820d7a255cb4edca68a9f82,PMC,Development of rapid immunochromatographic strip test for the detection of porcine epidemic diarrhoea virus,http://dx.doi.org/10.1136/vr.103959,PMC5738603,28993477,CC BY-NC,"Porcine epidemic diarrhoea virus (PEDV) causes acute and severe watery diarrhoea and dehydration, as well as 50–100 per cent mortality in piglets. For the PEDV diagnosis, a rapid test kit that is specific and sensitive to PEDV is critical to monitor this disease at pig farms. The present study aimed to develop an immunochromatographic assay (ICA) strip test for detecting PEDV in faecal swabs. The newly developed diagnostic test showed a detection limit of 10(4.0) TCID(50)/ml of PEDV. Using faecal swab samples, the relative sensitivity and specificity of the ICA kit were 95.0 per cent and 98.6 per cent, respectively, compared with those of real-time RT-PCR. In samples from piglets experimentally infected with PEDV, the results showed 100 per cent agreement with those found by real-time RT-PCR. Our developed test strip will be useful for rapid diagnosis and can be used for epidemiological surveillance of PEDV infection.",2017 Dec 2,"['Lyoo, Kwang-Soo', 'Yeom, Minjoo', 'Kim, Jungho', 'Kim, Donghyuk', 'Ha, Gunwoo', 'Na, Woonsung', 'Le, Van Phan', 'Song, Daesub']",Vet Rec,,,True
2407834245c872e91a78cdb9bd63ac8f81a49231,PMC,Combination treatment with quercetin and resveratrol attenuates high fat diet-induced obesity and associated inflammation in rats via the AMPKα1/SIRT1 signaling pathway,http://dx.doi.org/10.3892/etm.2017.5331,PMC5740593,29285143,CC BY-NC-ND,"Diet-induced obesity is associated with systemic inflammation, which is considered to originate predominantly from the adipose tissue. Quercetin and resveratrol are two dietary polyphenols that exhibit anti-inflammatory properties and anti-insulin resistance when administered in isolation or combination (CQR). It remains unknown whether CQR reduces high fat diet (HFD)-induced obesity and inflammation in rats. In the current study, 46 male Wistar rats were divided into two groups, one of which was fed a normal diet (ND, 5.4% fat, w/w) and one of which was fed a HFD (45% fat, w/w) for 3 weeks. Following removal of the 12 most obesity-resistant rats from the HFD group, the remaining rats were divided into two sub-groups: A HFD group and a HFD+CQR group (administered 120 mg/kg/day resveratrol and 240 mg/kg/day quercetin). The results revealed that the HFD+CQR group had significantly lower body weights at 11 weeks compared with the HFD group and had significantly reduced visceral adipose tissue weights and adipocyte sizes. Serum lipid profiles were also significantly ameliorated in the HFD+CQR group. CQR attenuated the expression of systemic proinflammatory adipokines, including leptin, tumor necrosis factor-α, monocyte chemoattractant protein-1 and interleukin-6. It also reduced the recruitment of mast cells to the epididyotic adipose tissue (EAT). Furthermore, CQR reversed the HFD-induced suppression of 5′-adenosine monophosphate-activated protein kinase α1 (AMPKα1) phosphorylation and sirtuin 1 (SIRT1) expression in EAT. In conclusion, CQR may suppress obesity and associated inflammation via the AMPKα1/SIRT1 signaling pathway in rats fed a HFD.",2017 Dec 18,"['Zhao, Le', 'Cen, Fang', 'Tian, Feng', 'Li, Min-Jie', 'Zhang, Qi', 'Shen, Hong-Yi', 'Shen, Xiang-Chun', 'Zhou, Ming-Mei', 'Du, Jun']",Exp Ther Med,,,True
29f72afab8b9894bede98ed862d87595374099c7,PMC,Histidine-rich Modification of a Scorpion-derived Peptide Improves Bioavailability and Inhibitory Activity against HSV-1,http://dx.doi.org/10.7150/thno.21425,PMC5743469,29290802,CC BY-NC,"Rationale: HSV is one of the most widespread human viral pathogens. HSV-1 infects a large portion of the human population and causes severe diseases. The current clinical treatment for HSV-1 is based on nucleoside analogues, the use of which is limited due to drug resistance, side effects and poor bioavailability. AMPs have been identified as potential antiviral agents that may overcome these limitations. Therefore, we screened anti-HSV-1 peptides from a scorpion-derived AMP library and engineered one candidate into a histidine-rich peptide with significantly improved antiviral activity and development potential. Methods: A venomous gland cDNA library was constructed from the scorpion Euscorpiops validus in the Yunnan Province of China. Six putative AMPs were characterized from this cDNA library, and the synthesized peptides were screened via plaque-forming assays to determine their virucidal potential. Time of addition experiments according to the infection progress of HSV-1 were used to identify the modes of action for peptides of interest. The histidine-rich modification was designed based on structural analysis of peptides by a helical wheel model and CD spectroscopy. Peptide cellular uptake and distribution were measured by flow cytometry and confocal microscopy, respectively. Results: The peptide Eval418 was found to have high clearance activity in an HSV-1 plaque reduction assay. Eval418 exhibited dose-dependent and time-dependent inactivation of HSV-1 and dose-dependent inhibition of HSV-1 attachment to host cells. However, Eval418 scarcely suppressed an established HSV-1 infection due to poor cellular uptake. We further designed and modified Eval418 into four histidine-rich derivative peptides with enhanced antiviral activities and lower cytotoxicities. All of the derivative peptides suppressed established HSV-1 infections. One of these peptides, Eval418-FH5, not only had strong viral inactivation activity and enhanced attachment inhibitory activity but also had high inhibitory activity against intracellular HSV-1, which was consistent with its improved intracellular uptake and distribution as confirmed by confocal microscopy and flow cytometry. Conclusion: We successfully identified an anti-HSV-1 peptide, Eval418, from a scorpion venom peptide library and designed a histidine-rich Eval418 derivative with significantly improved potential for further development as an anti-HSV-1 drug. This successful modification can provide a design strategy to improve the bioavailability, cellular distribution and antiviral activity of peptide agents.",2018 Jan 1,"['Zeng, Zhengyang', 'Zhang, Runhong', 'Hong, Wei', 'Cheng, Yuting', 'Wang, Huijuan', 'Lang, Yange', 'Ji, Zhenglin', 'Wu, Yingliang', 'Li, Wenxin', 'Xie, Youli', 'Cao, Zhijian']",Theranostics,,,True
e6f57228e6eddee590adad7a9b9021146e21c201,PMC,Sterile nodular panniculitis with lung and lymph node involvement in a Siberian tiger (Panthera tigris altica),http://dx.doi.org/10.1292/jvms.17-0262,PMC5745179,29081476,CC BY-NC-ND,"A 2- to 4-year-old uncastrated male Siberian tiger (Panthera tigris altica) bred in a local wild animal park presented with generalized clinical signs including abdominal pain, fever, lethargy, and anorexia, along with subcutaneous nodules along the trunk. The patient subsequently died of chronic, progressive dyspnea despite 45 days of antibiotic treatment. At necropsy, mesenteric fat inflammation and multiple subcutaneous, peritoneal, and intraabdominal nodules were observed. The lungs demonstrated congestion and heavy coagulation, and necrotic foci were observed on the cut surface. Histopathologically, the nodules were identified as granulomatous fatty tissue with numerous lymphocytes, infiltration with lipid-laden macrophages, and fibrosis. These changes were also noted in the lung. The etiology of this condition remains undetermined.",2017 Dec 30,"['HU, Shou-Ping', 'ZHANG, Zhuo', 'ZHANG, Jiao-Er', 'CAI, Xue-Hui', 'NAKAYAMA, Hiroyuki', 'HE, Xi-Jun']",J Vet Med Sci,,,True
0efea89bfa335dbd71828c4ed690012ca36fe1ce,PMC,Sterile nodular panniculitis with lung and lymph node involvement in a Siberian tiger (Panthera tigris altica),http://dx.doi.org/10.1292/jvms.17-0262,PMC5745179,29081476,CC BY-NC-ND,"A 2- to 4-year-old uncastrated male Siberian tiger (Panthera tigris altica) bred in a local wild animal park presented with generalized clinical signs including abdominal pain, fever, lethargy, and anorexia, along with subcutaneous nodules along the trunk. The patient subsequently died of chronic, progressive dyspnea despite 45 days of antibiotic treatment. At necropsy, mesenteric fat inflammation and multiple subcutaneous, peritoneal, and intraabdominal nodules were observed. The lungs demonstrated congestion and heavy coagulation, and necrotic foci were observed on the cut surface. Histopathologically, the nodules were identified as granulomatous fatty tissue with numerous lymphocytes, infiltration with lipid-laden macrophages, and fibrosis. These changes were also noted in the lung. The etiology of this condition remains undetermined.",2017 Dec 30,"['HU, Shou-Ping', 'ZHANG, Zhuo', 'ZHANG, Jiao-Er', 'CAI, Xue-Hui', 'NAKAYAMA, Hiroyuki', 'HE, Xi-Jun']",J Vet Med Sci,,,False
8ac886d6b20755b99f0d627f55536e4cc0d6107c,PMC,The Ebola clinical trials: a precedent for research ethics in disasters,http://dx.doi.org/10.1136/medethics-2016-103474,PMC5749307,27573153,CC BY-NC,"The West African Ebola epidemic has set in motion a collective endeavour to conduct accelerated clinical trials, testing unproven but potentially lifesaving interventions in the course of a major public health crisis. This unprecedented effort was supported by the recommendations of an ad hoc ethics panel convened in August 2014 by the WHO. By considering why and on what conditions the exceptional circumstances of the Ebola epidemic justified the use of unproven interventions, the panel's recommendations have challenged conventional thinking about therapeutic development and clinical research ethics. At the same time, unanswered ethical questions have emerged, in particular: (i) the specification of exceptional circumstances, (ii) the specification of unproven interventions, (iii) the goals of interventional research in terms of individual versus collective interests, (iv) the place of adaptive trial designs and (v) the exact meaning of compassionate use with unapproved interventions. Examination of these questions, in parallel with empirical data from research sites, will help build pragmatic foundations for disaster research ethics. Furthermore, the Ebola clinical trials signal an evolution in the current paradigms of therapeutic research, beyond the case of epidemic emergencies.",2018 Jan 29,"Calain, Philippe",J Med Ethics,,,True
5fedd08f111b588bface2d146740bad23bbbb3e3,PMC,Effects of Timely Control Intervention on the Spread of Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.24171/j.phrp.2017.8.6.03,PMC5749487,29354394,CC BY-NC-ND,"OBJECTIVES: The 2015 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreak in Korea caused major economic and social problems. The control intervention was conducted during the MERS-CoV outbreak in Korea immediately after the confirmation of the index case. This study investigates whether the early risk communication with the general public and mass media is an effective preventive strategy. METHODS: The SEIR (Susceptible, Exposed, Infectious, Recovered) model with estimated parameters for the time series data of the daily MERS-CoV incidence in Korea was considered from May to December 2015. For 10,000 stochastic simulations, the SEIR model was computed using the Gillespie algorithm. Depending on the time of control intervention on the 20th, 40th, and 60th days after the identification of the index case, the box plots of MERS-CoV incidences in Korea were computed, and the results were analyzed via ANOVA. RESULTS: The box plots showed that there was a significant difference between the non-intervention and intervention groups (the 20th day, 40th day, and 60th day groups) and seemed to show no significant difference based on the time of intervention. However, the ANOVA revealed that early intervention was a good strategy to control the disease. CONCLUSION: Appropriate risk communication can secure the confidence of the general public in the public health authorities.",2017 Dec 31,"['Choi, Ilsu', 'Lee, Dong Ho', 'Kim, Yongkuk']",Osong Public Health Res Perspect,,,True
921c3701d112c1aeef737e5d395e9996a81b9bff,PMC,Virus Database and Online Inquiry System Based on Natural Vectors,http://dx.doi.org/10.1177/1176934317746667,PMC5751915,29308007,CC BY-NC,"We construct a virus database called VirusDB (http://yaulab.math.tsinghua.edu.cn/VirusDB/) and an online inquiry system to serve people who are interested in viral classification and prediction. The database stores all viral genomes, their corresponding natural vectors, and the classification information of the single/multiple-segmented viral reference sequences downloaded from National Center for Biotechnology Information. The online inquiry system serves the purpose of computing natural vectors and their distances based on submitted genomes, providing an online interface for accessing and using the database for viral classification and prediction, and back-end processes for automatic and manual updating of database content to synchronize with GenBank. Submitted genomes data in FASTA format will be carried out and the prediction results with 5 closest neighbors and their classifications will be returned by email. Considering the one-to-one correspondence between sequence and natural vector, time efficiency, and high accuracy, natural vector is a significant advance compared with alignment methods, which makes VirusDB a useful database in further research.",2017 Dec 17,"['Dong, Rui', 'Zheng, Hui', 'Tian, Kun', 'Yau, Shek-Chung', 'Mao, Weiguang', 'Yu, Wenping', 'Yin, Changchuan', 'Yu, Chenglong', 'He, Rong Lucy', 'Yang, Jie', 'Yau, Stephen ST']",Evol Bioinform Online,,,True
d33bb76df69173f5bfcd44b6ae9cfeea362f0875,PMC,The Korean Influenza National Immunization Program: History and Present Status,http://dx.doi.org/10.3947/ic.2017.49.4.247,PMC5754334,29299891,CC BY-NC,"The Korean influenza national immunization program was first established as an interim program in 1997, administering the influenza vaccine to low-income elderly adults. In 2005, the program assumed its present form of providing free influenza vaccination to adults aged ≥65 years. After turning over the influenza vaccination for elderly adults to the private sectors in 2015, the influenza vaccination coverage rate among this population increased to >80%. In addition, after the 2009 H1N1 influenza epidemic crisis, the vaccine was domestically produced. By reaching a 75% vaccination coverage rate in the target groups, it was possible to put an end to the influenza pandemic and fix the shortcomings of the system that existed at that time. The influenza vaccination program, provided free of cost, was extended to include infants aged <12 months in 2016 and ≤59 months in 2017 in order to reduce the influenza burden in these populations. However, the vaccine effectiveness remains low despite the high vaccination rates in elderly adults. Therefore, several areas, such as the adoption of quadrivalent influenza vaccine, adjuvanted influenza vaccine, and high-dose influenza vaccine and the expansion of vaccination target groups, still need to be addressed.",2017 Dec 21,"['Yun, Jae-Won', 'Noh, Ji Yun', 'Song, Joon Young', 'Chun, Chaemin', 'Kim, Yunju', 'Cheong, Hee Jin']",Infect Chemother,,,True
9572c5aae9bef12492279374fa1f562a03eafd08,PMC,Guidelines for the Antibiotic Use in Adults with Acute Upper Respiratory Tract Infections,http://dx.doi.org/10.3947/ic.2017.49.4.326,PMC5754344,29299900,CC BY-NC,"These guidelines were developed as part of the 2016 Policy Research Servicing Project by the Korea Centers for Disease Control and Prevention. A multidisciplinary approach was taken to formulate this guideline to provide practical information about the diagnosis and treatment of adults with acute upper respiratory tract infection, with the ultimate aim to promote the appropriate use of antibiotics. The formulation of this guideline was based on a systematic literature review and analysis of the latest research findings to facilitate evidence-based practice, and focused on key questions to help clinicians obtain solutions to clinical questions that may arise during the care of a patient. These guidelines mainly cover the subjects on the assessment of antibiotic indications and appropriate selection of antibiotics for adult patients with acute pharyngotonsillitis or acute sinusitis.",2017 Dec 26,"['Yoon, Young Kyung', 'Park, Chan-Soon', 'Kim, Jae Wook', 'Hwang, Kyurin', 'Lee, Sei Young', 'Kim, Tae Hoon', 'Park, Do-Yang', 'Kim, Hyun Jun', 'Kim, Dong-Young', 'Lee, Hyun Jong', 'Shin, Hyun-Young', 'You, Yong Kyu', 'Park, Dong-Ah', 'Kim, Shin-Woo']",Infect Chemother,,,True
496bfe6fe82dca285afe74c0202ad9498b41370c,PMC,Guidelines for the Antibiotic Use in Adults with Acute Upper Respiratory Tract Infections,http://dx.doi.org/10.3947/ic.2017.49.4.326,PMC5754344,29299900,CC BY-NC,"These guidelines were developed as part of the 2016 Policy Research Servicing Project by the Korea Centers for Disease Control and Prevention. A multidisciplinary approach was taken to formulate this guideline to provide practical information about the diagnosis and treatment of adults with acute upper respiratory tract infection, with the ultimate aim to promote the appropriate use of antibiotics. The formulation of this guideline was based on a systematic literature review and analysis of the latest research findings to facilitate evidence-based practice, and focused on key questions to help clinicians obtain solutions to clinical questions that may arise during the care of a patient. These guidelines mainly cover the subjects on the assessment of antibiotic indications and appropriate selection of antibiotics for adult patients with acute pharyngotonsillitis or acute sinusitis.",2017 Dec 26,"['Yoon, Young Kyung', 'Park, Chan-Soon', 'Kim, Jae Wook', 'Hwang, Kyurin', 'Lee, Sei Young', 'Kim, Tae Hoon', 'Park, Do-Yang', 'Kim, Hyun Jun', 'Kim, Dong-Young', 'Lee, Hyun Jong', 'Shin, Hyun-Young', 'You, Yong Kyu', 'Park, Dong-Ah', 'Kim, Shin-Woo']",Infect Chemother,,,True
97ccba72ca8eb3f5e5ab93b441f4d8c5fbc944e9,PMC,Guidelines for the Antibiotic Use in Adults with Acute Upper Respiratory Tract Infections,http://dx.doi.org/10.3947/ic.2017.49.4.326,PMC5754344,29299900,CC BY-NC,"These guidelines were developed as part of the 2016 Policy Research Servicing Project by the Korea Centers for Disease Control and Prevention. A multidisciplinary approach was taken to formulate this guideline to provide practical information about the diagnosis and treatment of adults with acute upper respiratory tract infection, with the ultimate aim to promote the appropriate use of antibiotics. The formulation of this guideline was based on a systematic literature review and analysis of the latest research findings to facilitate evidence-based practice, and focused on key questions to help clinicians obtain solutions to clinical questions that may arise during the care of a patient. These guidelines mainly cover the subjects on the assessment of antibiotic indications and appropriate selection of antibiotics for adult patients with acute pharyngotonsillitis or acute sinusitis.",2017 Dec 26,"['Yoon, Young Kyung', 'Park, Chan-Soon', 'Kim, Jae Wook', 'Hwang, Kyurin', 'Lee, Sei Young', 'Kim, Tae Hoon', 'Park, Do-Yang', 'Kim, Hyun Jun', 'Kim, Dong-Young', 'Lee, Hyun Jong', 'Shin, Hyun-Young', 'You, Yong Kyu', 'Park, Dong-Ah', 'Kim, Shin-Woo']",Infect Chemother,,,False
c259227a2fb2036651025b4cf35fbd2d2942d26c,PMC,The Fractionated Toona sinensis Leaf Extract Induces Apoptosis of Human Osteosarcoma Cells and Inhibits Tumor Growth in a Murine Xenograft Model,http://dx.doi.org/10.1177/1534735416675951,PMC5759936,27879376,CC BY-NC,"Background: Osteosarcoma is a malignant bone tumor prevalent in adolescents with poor prognosis. Toona sinensis showed potent antiproliferation effect on lung, melatonin, ovary, colon, and liver cancers. However, the effects of the species on osteosarcoma cells are rarely investigated. Results: In this study, we found fraction 1 of Toona sinensis leaf (TSL-1) resulted in inhibition of cell viability in MG-63, Saos-2, and U2OS osteosarcoma cell lines, while it only caused a moderate suppressive effect on normal osteoblasts. In addition, TSL-1 significantly elevated lactate dehydrogenase leakage and induced apoptosis and necrosis in Saos-2 cells. TSL-1 increased mRNA expression of pro-apoptotic factor Bad. Most important, TSL-1 significantly suppressed Saos-2 xenograft tumor growth in nude mice by increasing caspase-3. The IC-50 of TSL-1 for the 3 tested osteosarcoma cells is around 1/9 of that for lung cancer cells. Conclusion: We demonstrated that TSL-1, a fractionated extract from TSL, caused significant cytotoxicity to osteosarcoma cells due to apoptosis. In vivo xenograft study showed that TSL-1 suppressed the growth of osteosarcoma cells at least in part by inducing apoptosis. Our results indicate that TSL-1 has potential to be a promising anti-osteosarcoma adjuvant functional plant extract.",2016 Nov 22,"['Chen, Chung-Hwan', 'Li, Ching-Ju', 'Tai, I-Chun', 'Lin, Xiao-Hui', 'Hsu, Hseng-Kuang', 'Ho, Mei-Ling']",Integr Cancer Ther,,,True
5e3baaac3cdc7bfad5ed84c6e7cc324a8396ebb9,PMC,Toona sinensis Inhibits Murine Leukemia WEHI-3 Cells and Promotes Immune Response In Vivo,http://dx.doi.org/10.1177/1534735416642863,PMC5759945,27151590,CC BY-NC,"Toona sinensis (TS) is one of the most popular vegetarian dishes in Taiwan. It has been shown to exhibit antioxidant, antiangiogenic, antiatherosclerotic, and anticancer properties. In this study, we demonstrated the ability of aqueous leaf extracts from TS to promote immune responses in BALB/c mice and to exhibit anti-leukemia activity in murine WEHI-3 cells. BALB/c mice were injected intravenously with WEHI-3 cells and then treated orally with TS (50 mg/kg). In vivo study showed that TS treatment reduced liver and spleen enlargement in WEHI-3 bearing mice compared with the untreated group. Furthermore, TS also decreased white blood cells (WBC), indicating inhibition of differentiation of the precursor of macrophages in WEHI-3 bearing mice. Treatment of WEHI-3 cells with TS (0-75 μg/mL for 24 hours) significantly reduced cell viability. Furthermore, TS treatment–induced late apoptosis was confirmed by Annexin-V/PI staining. Western blot analyses revealed that treatment of WEHI-3 cells with TS statistically increased the protein expression level of cytochrome c in the cytoplasm and activates caspase-3. Notably, TS treatment caused a dramatic reduction in Bcl-2 and increase in Bax protein levels. TS may disturb the Bcl-2 and Bax protein ratio and induce apoptosis. This reports confirms the antitumor activity of this nutritious vegetable potentially against leukemia.",2016 May 4,"['Yang, Hsin-Ling', 'Thiyagarajan, Varadharajan', 'Liao, Jiunn-Wang', 'Chu, Yu-Lin', 'Chang, Chia-Ting', 'Huang, Pei-Jane', 'Hsu, Chih-Jung', 'Hseu, You-Cheng']",Integr Cancer Ther,,,True
3740de0a7774ae09eb39857f90d261130ce5ed08,PMC,Development of a validated UPLC–qTOF-MS/MS method for determination of bioactive constituent from Glycyrrhiza glabra,http://dx.doi.org/10.1016/j.jpha.2013.01.001,PMC5760977,29403818,CC BY-NC-ND,"An ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC–qTOF-MS/MS) method was developed and validated for the simultaneous determination of glycyrrhizin and glycyrrhetic acid. These analytes were separated on a reverse phase C18 column using a mobile phase of acetonitrile:2% acetic acid in water (75:25, v/v) with a flow rate of 200 μL/min. The qTOF-MS was operated under multiple reaction monitoring (MRM) mode using the electrospray ionization (ESI) technique with positive ion polarity. A comparison of three different extraction techniques i.e. accelerated solvent extraction (ASE), extraction under ultrasonic waves (USW) and the classical extraction by percolation (CE) method was done and quantification of these extracts was also carried out by the proposed method.",2013 Jun 11,"['Gupta, D.K.', 'Verma, M.K.', 'Anand, R.', 'Khajuria, R.K.']",J Pharm Anal,,,False
3b6d953fa2770589cb1f699047f2d94990cfa4ad,PMC,Psychological Flexibility of Nurses in a Cancer Hospital: Preliminary Validation of a Chinese Version of the Work-related Acceptance and Action Questionnaire,http://dx.doi.org/10.4103/apjon.apjon_62_17,PMC5763445,29379839,CC BY-NC-SA,"OBJECTIVE: To translate the English work-related acceptance and action questionnaire (WAAQ), make cross-cultural adaptations, and examine its psychometric properties when used by Chinese oncology nurses. METHODS: After translation, the psychometric properties of the Chinese WAAQ were analyzed among 417 nurses, and content validity was determined by six experts. RESULTS: Item-level content validity index (CVI) values were between 0.83 and 1.00; scale-level CVI/universal agreement (S-CVI/UA) and S-CVI/average were 0.86 and 0.98, respectively, which implicated a good content validity. The correlation of the Chinese WAAQ with AAQ-II (r(s) = −0.247, P < 0.001) suggested criterion validity, and those with General Health Questionnaire-12 (−0.250, <0.001) and general self-efficacy scale (0.491, <0.001) and Utrecht work engagement scale (UWES) (0.439, <0.001) suggested convergent validity. Exploratory factor analysis identified a seven-item, one-factor structure of WAAQ. The Chinese version of WAAQ had high internal consistency (Cronbach's α = 0.920), with an item-total correlation coefficient of 0.702–0.828 (P < 0.05), split-half reliability of 0.933, and test-retest reliability of 0.772. CONCLUSIONS: The Chinese WAAQ is a reliable and valid tool for assessing psychological flexibility in Chinese oncology nurses.",2018 Jan-Mar,"['Xu, Xianghua', 'Liu, Xiangyu', 'Ou, Meijun', 'Xie, Chanjuan', 'Chen, Yongyi']",Asia Pac J Oncol Nurs,,,True
e4ff00b9e8eec242803472b134846a7dbec01989,PMC,"Phylogenetic Distribution of CMP-Neu5Ac Hydroxylase (CMAH), the Enzyme Synthetizing the Proinflammatory Human Xenoantigen Neu5Gc",http://dx.doi.org/10.1093/gbe/evx251,PMC5767959,29206915,CC BY-NC,"The enzyme CMP-N-acetylneuraminic acid hydroxylase (CMAH) is responsible for the synthesis of N-glycolylneuraminic acid (Neu5Gc), a sialic acid present on the cell surface proteins of most deuterostomes. The CMAH gene is thought to be present in most deuterostomes, but it has been inactivated in a number of lineages, including humans. The inability of humans to synthesize Neu5Gc has had several evolutionary and biomedical implications. Remarkably, Neu5Gc is a xenoantigen for humans, and consumption of Neu5Gc-containing foods, such as red meats, may promote inflammation, arthritis, and cancer. Likewise, xenotransplantation of organs producing Neu5Gc can result in inflammation and organ rejection. Therefore, knowing what animal species contain a functional CMAH gene, and are thus capable of endogenous Neu5Gc synthesis, has potentially far-reaching implications. In addition to humans, other lineages are known, or suspected, to have lost CMAH; however, to date reports of absent and pseudogenic CMAH genes are restricted to a handful of species. Here, we analyze all available genomic data for nondeuterostomes, and 322 deuterostome genomes, to ascertain the phylogenetic distribution of CMAH. Among nondeuterostomes, we found CMAH homologs in two green algae and a few prokaryotes. Within deuterostomes, putatively functional CMAH homologs are present in 184 of the studied genomes, and a total of 31 independent gene losses/pseudogenization events were inferred. Our work produces a list of animals inferred to be free from endogenous Neu5Gc based on the absence of CMAH homologs and are thus potential candidates for human consumption, xenotransplantation research, and model organisms for investigation of human diseases.",2017 Dec 30,"['Peri, Sateesh', 'Kulkarni, Asmita', 'Feyertag, Felix', 'Berninsone, Patricia M', 'Alvarez-Ponce, David']",Genome Biol Evol,,,True
60bcf8aea7134c49453a05d2b9d52728cc6edcd6,PMC,Porcine reproductive and respiratory syndrome virus suppresses post-transcriptionally the protein expression of IFN-β by upregulating cellular microRNAs in porcine alveolar macrophages in vitro,http://dx.doi.org/10.3892/etm.2017.5397,PMC5769220,29387185,CC BY-NC-ND,"Porcine reproductive and respiratory syndrome virus (PRRSV) has been recognized to inhibit the response of type I interferon (IFN) both in vivo and in vitro. However, the post-transcriptional mechanism by which PRRSV suppresses type I IFN induction in virus-infected host cells remains unclear. The present study first demonstrated that PRRSV inhibited post-transcriptionally the protein induction of IFN-β in primary porcine alveolar macrophages (PAMs) during early infection, and the inhibition effect mediated by the Chinese highly pathogenic (HP)-PRRSV was stronger. Next, we analyzed the cellular microRNA (miRNA)-modulated protein expression of porcine IFN-β by dual firefly/Renilla luciferase reporter assay, transfection of miRNA mimics and inhibitor assay and polyinosinic-polycytidylic acid (poly I:C) treatment of PAMs, showing that porcine miRNAs including let-7b, miR-26a, miR-34a and miR-145 are able to inhibit IFN-β protein expression in primary PAMs by directly targeting sequences within the porcine IFN-β 3′UTR locating at 160–181, 9–31, 27–47 and 12–32 bp, respectively. Finally, we confirmed that let-7b, miR-26a, miR-34a and miR-145, were upregulated in PRRSV-infected PAMs early in vitro, and the expression level of these miRNAs in HP-PRRSV JXwn06-infected PAMs were higher than those in low pathogenic PRRSV HB-1/3.9-infected PAMs. The endogenous cellular miRNA-mediated inhibition of IFN-β induction in PRRSV-infected PAMs early could be relieved by miRNA antagonists. Taken together, our findings suggest for the first time that PRRSV can suppress post-transcriptionally protein expression of IFN-β by upregulating cellular miRNAs in PAMs in vitro, providing novel insight into mechanisms in relation to the PRRSV-mediated immunomodulation of porcine innate immunity.",2018 Jan 30,"['Wang, Lilin', 'Zhou, Lei', 'Hu, Dongmei', 'Ge, Xinna', 'Guo, Xin', 'Yang, Hanchun']",Exp Ther Med,,,True
5f2fed24630132d29e1336b240edc9ab68e459aa,PMC,Simulation-based Training as Perceived by Young Anesthesiology and Intensive Care Residents,http://dx.doi.org/10.1515/jccm-2017-0007,PMC5769893,29967863,CC BY-NC-ND,,2017 Feb 18,"['Copotoiu, Sanda-Maria', 'Copotoiu, Ruxandra']",J Crit Care Med (Targu Mures),,,True
4971940ab68e4950b28410a208166900e8ba9c07,PMC,"Circulation of canine parvovirus among dogs living in human-wildlife interface in the Atlantic forest biome, Brazil",http://dx.doi.org/10.1016/j.heliyon.2017.e00491,PMC5772843,29387822,CC BY-NC-ND,"Despite of the role of domestic dogs as reservoirs for threatening viral diseases for wild carnivores, few studies have focused to identify circulation of viruses among dogs living in human/wildlife interfaces. To identify canine parvovirus (CPV) types circulating in dogs living in an Atlantic forest biome, faecal samples (n = 100) were collected at the same period (one week) corresponding to each of four areas, during 2014 to 2016 and corresponded to 100 different individuals. CPV was isolated in cell culture from 67 out 100 (67%) samples from healthy dogs. Cytopathic effects were characterized by total or partial cell culture lysis. Genome sequences of CPV-2a (10%), CPV-2b (7%) and CPV-2c (50%) were concomitantly detected by PCR and nucleotide sequencing. The current study addresses the importance of monitoring CPV circulation among dogs presenting potential contact with wildlife species.",2018 Jan 11,"['Vieira, Flávia V.', 'Hoffmann, Daniel J.', 'Fabri, Carolina U.F.', 'Bresciani, Katia D.S.', 'Gameiro, Roberto', 'Flores, Eduardo F.', 'Cardoso, Tereza C.']",Heliyon,,,False
b73f2926cc2e4d4d9dc0c41e90c1df1fee07039c,PMC,"Seroprevalence of Dirofilaria immitis in Cats from Liaoning Province, Northeastern China",http://dx.doi.org/10.3347/kjp.2017.55.6.673,PMC5776902,29320824,CC BY-NC,"The present study was performed to investigate the seroprevalence and risk factors for Dirofilaria immitis infection in cats from Liaoning province, northeastern China. From October 2014 to September 2016, sera of 651 cats, including 364 domestic cats and 287 feral cats (332 females and 319 males) were assessed. They were tested for the presence of D. immitis antigen using SNAP Heartworm RT test kit. In this population, the average prevalence was 4.5%. Age and rearing conditions (feral or domestic) were found to be associated with the prevalence of D. immitis. The prevalence was significantly higher in feral cats compared with domestic cats (8.4% vs 1.4%, P<0.01). There was no significant difference between males and females (4.7% vs 4.2%, P>0.05), but older cats (≥3 years old) showed a statistically higher prevalence compared with younger cats (<3 years old) in feral populations (16.8 vs 2.4%, P<0.01), while the difference between the age groups was not statistically significant in domestic cats (2.4% vs 0.51%, P>0.05), all these results suggest that outdoor exposure time may be one of the most important factors for D. immitis prevalence in cats. Results reveal that D. immitis are prevalence in domestic and feral cats in northeastern China, which indicates that appropriate preventive measures should be taken to decrease the incidence of feline heartworm disease in Liaoning province, northeastern China.",2017 Dec 31,"['Hou, Honglie', 'Cao, Lili', 'Ren, Wenzhi', 'Wang, Dansheng', 'Ding, He', 'You, Juan', 'Yao, Xinhua', 'Dong, Hang', 'Guo, Yanbing', 'Yuan, Shuxian', 'Zhang, Xichen', 'Gong, Pengtao']",Korean J Parasitol,,,True
b8b13fd5a49e6193135315c97de14fb7b9936286,PMC,Designing and building oncolytic viruses,http://dx.doi.org/10.2217/fvl-2016-0129,PMC5779534,29387140,CC BY-NC-ND,"Oncolytic viruses (OVs) are engineered and/or evolved to propagate selectively in cancerous tissues. They have a dual mechanism of action; direct killing of infected cancer cells cross-primes anticancer immunity to boost the killing of uninfected cancer cells. The goal of the field is to develop OVs that are easily manufactured, efficiently delivered to disseminated sites of cancer growth, undergo rapid intratumoral spread, selectively kill tumor cells, cause no collateral damage and pose no risk of transmission in the population. Here we discuss the many virus engineering strategies that are being pursued to optimize delivery, intratumoral spread and safety of OVs derived from different virus families. With continued progress, OVs have the potential to transform the paradigm of cancer care.",2017 Apr 31,"['Maroun, Justin', 'Muñoz-Alía, Miguel', 'Ammayappan, Arun', 'Schulze, Autumn', 'Peng, Kah-Whye', 'Russell, Stephen']",Future Virol,,,True
0f0bb7346d45679cc1bb2435c66d5ad3ef52c108,PMC,n-butanol extract from Folium isatidis inhibits the lipopolysaccharide-induced downregulation of CXCR1 and CXCR2 on human neutrophils,http://dx.doi.org/10.3892/mmr.2017.7870,PMC5780124,29115434,CC BY-NC-ND,"Neutrophils, immune cells crucial for protecting against invading pathogens, are important in sepsis. Neutrophil migration is regulated by chemokine receptors and their cognate ligands. Our previous study investigated the effect of n-butanol extract from Folium isatidis on lipopolysaccharide (LPS)-induced septic shock. The present study stimulated neutrophils with LPS to explore the influence of LPS on cell. Neutrophils were then pretreated with n-butanol extract from Folium isatidis followed by LPS to examine the effect of this extract on neutrophil chemotaxis. The results showed that LPS decreased the expression levels of CXC-chemokine receptor (CXCR)1, CXCR2 and L-selectin (CD62L), and increased the expression of interleukin-8 (IL-8) by neutrophils. The addition of n-butanol extract from Folium isatidis inhibited this LPS-induced downregulation of CXCR1, CXCR2 and CD62L, and decreased the expression of IL-8 on neutrophils. In addition, n-butanol extract promoted myeloperoxidase activity in neutrophils. Taken together, LPS downregulated the expression of chemokine receptors, leading to the failure of neutrophils to migrate to sites of infection. The addition of n-butanol extract, which promoted the ability of neutrophils to migrate, is a natural product and potential therapeutic agent with which to target neutrophil chemotaxis during LPS stimulation.",2018 Jan 25,"['Wu, Beibei', 'Wang, Liyin', 'Jiang, Lili', 'Dong, Lili', 'Xu, Fengli', 'Lu, Yili', 'Jin, Jiahui', 'Wang, Zhanyue', 'Liang, Guang', 'Shan, Xiaoou']",Mol Med Rep,,,True
9bad339dd5a9605d61cc773ecfe0c65d4402f4b7,PMC,Seasonal Influenza Forecasting in Real Time Using the Incidence Decay With Exponential Adjustment Model,http://dx.doi.org/10.1093/ofid/ofx166,PMC5781299,29497629,CC BY-NC-ND,"BACKGROUND: Seasonal influenza epidemics occur frequently. Rapid characterization of seasonal dynamics and forecasting of epidemic peaks and final sizes could help support real-time decision-making related to vaccination and other control measures. Real-time forecasting remains challenging. METHODS: We used the previously described “incidence decay with exponential adjustment” (IDEA) model, a 2-parameter phenomenological model, to evaluate the characteristics of the 2015–2016 influenza season in 4 Canadian jurisdictions: the Provinces of Alberta, Nova Scotia and Ontario, and the City of Ottawa. Model fits were updated weekly with receipt of incident virologically confirmed case counts. Best-fit models were used to project seasonal influenza peaks and epidemic final sizes. RESULTS: The 2015–2016 influenza season was mild and late-peaking. Parameter estimates generated through fitting were consistent in the 2 largest jurisdictions (Ontario and Alberta) and with pooled data including Nova Scotia counts (R(0) approximately 1.4 for all fits). Lower R(0) estimates were generated in Nova Scotia and Ottawa. Final size projections that made use of complete time series were accurate to within 6% of true final sizes, but final size was using pre-peak data. Projections of epidemic peaks stabilized before the true epidemic peak, but these were persistently early (~2 weeks) relative to the true peak. CONCLUSIONS: A simple, 2-parameter influenza model provided reasonably accurate real-time projections of influenza seasonal dynamics in an atypically late, mild influenza season. Challenges are similar to those seen with more complex forecasting methodologies. Future work includes identification of seasonal characteristics associated with variability in model performance.",2017 Sep 27,"['Nasserie, Tahmina', 'Tuite, Ashleigh R', 'Whitmore, Lindsay', 'Hatchette, Todd', 'Drews, Steven J', 'Peci, Adriana', 'Kwong, Jeffrey C', 'Friedman, Dara', 'Garber, Gary', 'Gubbay, Jonathan', 'Fisman, David N']",Open Forum Infect Dis,,,True
165792449dc650fba4a923f3a94a851754a7bcb7,PMC,Strengthening global health security by embedding the International Health Regulations requirements into national health systems,http://dx.doi.org/10.1136/bmjgh-2017-000656,PMC5783036,29379650,CC BY-NC,"The International Health Regulations (IHR) 2005, as the overarching instrument for global health security, are designed to prevent and cope with major international public health threats. But poor implementation in countries hampers their effectiveness. In the wake of a number of major international health crises, such as the 2014 Ebola and 2016 Zika outbreaks, and the findings of a number of high-level assessments of the global response to these crises, it has become clear that there is a need for more joined-up thinking between health system strengthening activities and health security efforts for prevention, alert and response. WHO is working directly with its Member States to promote this approach, more specifically around how to better embed the IHR (2005) core capacities into the main health system functions. This paper looks at how and where the intersections between the IHR and the health system can be best leveraged towards developing greater health system resilience. This merging of approaches is a key component in pursuit of Universal Health Coverage and strengthened global health security as two mutually reinforcing agendas.",2018 Jan 20,"['Kluge, Hans', 'Martín-Moreno, Jose Maria', 'Emiroglu, Nedret', 'Rodier, Guenael', 'Kelley, Edward', 'Vujnovic, Melitta', 'Permanand, Govin']",BMJ Glob Health,,,True
3588b1ead834ac96e69e3f3e84b422dc3e43c068,PMC,"Bispecific antibodies: design, therapy, perspectives",http://dx.doi.org/10.2147/DDDT.S151282,PMC5784585,29403265,CC BY-NC,"Antibodies (Abs) containing two different antigen-binding sites in one molecule are called bispecific. Bispecific Abs (BsAbs) were first described in the 1960s, the first monoclonal BsAbs were generated in the 1980s by hybridoma technology, and the first article describing the therapeutic use of BsAbs was published in 1992, but the number of papers devoted to BsAbs has increased significantly in the last 10 years. Particular interest in BsAbs is due to their therapeutic use. In the last decade, two BsAbs – catumaxomab in 2009 and blinatumomab in 2014, were approved for therapeutic use. Papers published in recent years have been devoted to various methods of BsAb generation by genetic engineering and chemical conjugation, and describe preclinical and clinical trials of these drugs in a variety of diseases. This review considers diverse BsAb-production methods, describes features of therapeutic BsAbs approved for medical use, and summarizes the prospects of practical application of promising new BsAbs.",2018 Jan 22,"['Sedykh, Sergey E', 'Prinz, Victor V', 'Buneva, Valentina N', 'Nevinsky, Georgy A']",Drug Des Devel Ther,,,True
1560d77c8e16b3b283f328b1c3de5513014522e9,PMC,Development and Validation of the Korean Version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients with Non-muscle Invasive Bladder Cancer: EORTC QLQ-NMIBC24,http://dx.doi.org/10.4143/crt.2016.594,PMC5784644,28279061,CC BY-NC,"PURPOSE: We aimed to evaluate psychometric properties of the Korean version of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-NMIBC24 when applied to Korean non-muscle invasive bladder cancer (NMIBC) patients. MATERIALS AND METHODS: A total of 249 patients who underwent curative transurethral resection of bladder tumor (TURBT) for primary or recurrent NMIBC were asked to complete the Korean version of EORTC QLQ-C30 and -NMIBC24 questionnaires three times (preoperative, post-TURBT 3 months and 6 months). Linguistic validation and psychometric evaluation of the questionnaire was conducted. RESULTS: Multitrait scaling analysis confirmed satisfactory construct validity in five scales except the malaise scale. Internal consistency was good (Cronbach’s alpha ≥ 0.70) for the five scales except the malaise scale at the all three time points. Known-group comparison analyses showed better quality-of-life (QOL) scores in patients with higher performance status as expected, and better sexual function in men than women (p < 0.05). Most of the scales had low correlations (< 0.40) with the scales in QLQ-C30 showing divergent validity, except for malaise scale which showed higher correlations (0.42 to 0.60). Responsiveness to change was consistent with clinical implications over time after TURBT. CONCLUSION: The Korean version of the EORTC QLQ-NMIBC24 has good reliability and cross-cultural validity for measuring various QOL aspects that can be self-administered to Korean NMIBC patients undergoing TURBT.",2018 Jan 10,"['Park, Jinsung', 'Shin, Dong Wook', 'Kim, Tae-Hwan', 'Jung, Seung Il', 'Nam, Jong Kil', 'Park, Seung Chol', 'Hong, Sungwoo', 'Jung, Jae Hung', 'Kim, Hongwook', 'Kim, Won Tae']",Cancer Res Treat,,,True
e75a5247e38dcdbb6e6a03fca1a920923e62cfe4,PMC,Hospital-based Influenza Morbidity and Mortality (HIMM) Surveillance for A/H7N9 Influenza Virus Infection in Returning Travelers,http://dx.doi.org/10.3346/jkms.2018.33.e49,PMC5785625,29359537,CC BY-NC,"Since 2013, the Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system began a H7N9 influenza surveillance scheme for returning travelers in addition to pre-existing emergency room (ER)-based influenza-like illness (ILI) surveillance and severe acute respiratory infection (SARI) surveillance. Although limited to eastern China, avian A/H7N9 influenza virus is considered to have the highest pandemic potential among currently circulating influenza viruses. During the study period between October 1st, 2013 and April 30th, 2016, 11 cases presented with ILI within seven days of travel return. These patients visited China, Hong Kong, or neighboring Southeast Asian countries, but none of them visited a livestock market. Seasonal influenza virus (54.5%, 6 among 11) was the most common cause of ILI among returning travelers, and avian A/H7N9 influenza virus was not detected during the study period.",2018 Jan 8,"['Song, Joon Young', 'Noh, Ji Yun', 'Lee, Jacob', 'Woo, Heung Jeong', 'Lee, Jin Soo', 'Wie, Seong-Heon', 'Kim, Young Keun', 'Jeong, Hye Won', 'Kim, Shin Woo', 'Lee, Sun Hee', 'Park, Kyung-Hwa', 'Kang, Seong Hui', 'Kee, Sae Yoon', 'Kim, Tae Hyong', 'Choo, Eun Ju', 'Lee, Han Sol', 'Choi, Won Suk', 'Cheong, Hee Jin', 'Kim, Woo Joo']",J Korean Med Sci,,,True
252878458973ebf8c4a149447b2887f0e553e7b5,PMC,Successful Treatment of Disseminated Nocardiosis Caused by Nocardia veterana in a Dog,http://dx.doi.org/10.1111/jvim.14855,PMC5787162,29105868,CC BY-NC,"A 5‐year‐old male castrated Lhasa Apso cross was evaluated for a 1‐month history of inappetence, lethargy, gagging, and progressive right thoracic limb lameness. Synovial fluid analysis revealed nonseptic suppurative inflammation, and a diagnosis of immune‐mediated polyarthritis (IMPA) was made. After 3 months of treatment with prednisone and later cyclosporine, the dog developed multiple firm cutaneous and subcutaneous masses and a focal mass within the jejunum. Cultures of blood, urine, skin lesions, and the jejunal mass identified Nocardia veterana by matrix‐absorption laser desorption ionization‐time‐of‐flight mass spectrometry (MALDI‐TOF MS) and allowed for earlier identification of the organism compared to more traditional secA1 gene sequencing. Immunosuppressive drug treatment was discontinued, and the dog was treated for 3 months by administration of trimethoprim‐sulfamethoxazole (TMS). No recurrence of clinical signs was reported 1 year later. This case report highlights the clinical utility of MALDI‐TOF MS, particularly for the rapid identification of slow‐growing, fastidious organisms.",2018 Nov 4 Jan-Feb,"['Yaemsiri, S.', 'Sykes, J.E.']",J Vet Intern Med,,,True
84dc4e9ee5f8dd324d2d436d7c07c7d0044a58a4,PMC,"Research Communications of the 27(th) ECVIM‐CA Congress: Intercontinental, Saint Julian's, Malta, 14th to 16th September 2017",http://dx.doi.org/10.1111/jvim.14858,PMC5787188,,CC BY-NC,,2018 Nov 7 Jan-Feb,,J Vet Intern Med,,,True
e9624e13395487f67a1beb7c42f952e1f0b475bb,PMC,Successful treatment of Providencia rettgeri cholecystitis and neutrophilic cholangitis in a cat,http://dx.doi.org/10.1177/2055116917750763,PMC5788108,29399368,CC BY-NC,"CASE SUMMARY: A 15-year-old male neutered domestic shorthair cat was presented with a recent history of seizures, diarrhoea, lethargy, fever and jaundice. Marked elevation of liver enzyme activity was present and ultrasound examination was suggestive of cholecystitis and hepatitis. Neutrophilic cholangitis was confirmed on histopathology of liver biopsies. Bile culture identified a monomicrobial infection with Providencia rettgeri, which was resistant to multiple antimicrobial agents. The cat was treated with oral pradofloxacin for 4 weeks and remained well 4 months later. RELEVANCE AND NOVEL INFORMATION: Providencia species are rarely reported in the veterinary literature and are an uncommon cause of disease in humans. The significance of this species in humans relates to the high prevalence of antimicrobial resistance. This is the first report of P rettgeri causing clinical illness in a cat and highlights the importance of bile cultures in hepatic disease.",2018 Jan 23,"['Newton, Patricia L', 'Fry, Darren R']",JFMS Open Rep,,,True
ddb9dfdd7b98f39f282347a314eefb4a04e722f3,PMC,Effects of Module Development and Role Play Course on Clinical Practice Examination Scores during a 4th Year Clerkship,http://dx.doi.org/10.4082/kjfm.2018.39.1.23,PMC5788842,29383208,CC BY-NC,"BACKGROUND: After introduction of clinical skills assessment in the Korean Medical Licensing Examination, medical schools have reinforced both experiential learning with real patients and preparatory programs. This study was conducted to investigate whether a clinical practice examination (CPX) preparation program improves students' CPX score in terms of case specificity. METHODS: One hundred and thirteen senior students in a medical school participated in this study. During the fourth-year clerkship, 28 students (24.8%) from three rotation groups took a 3-day CPX preparation course consisting of module development, role play, and comprehensive physical exam skills training. Eleven rotation groups (n=85) were compared as control. Both the intervention and control group took two comprehensive CPXs before and after the clerkship was completed. RESULTS: There was no significant difference in age, sex, and school type between the two groups. On pre-test CPX, there was no significant difference in total and sectional scores between the two groups. On post-test CPX, total scores of the intervention group were higher than those of the control groups (69.5±4.3 vs. 67.5±4.4, P<0.05). History taking scores were higher in intervention groups (70.0±6.0 vs. 66.0±6.6, P=0.01). The station scores of vaginal discharge with case similarity were higher in the intervention groups (73.0±6.3 vs. 68.9±9.3, P=0.03). CONCLUSION: A short CPX preparation course improved history taking ability, but its effect was greater only in a specific case, similar to the pre-course case. Whether this effect was due to the test experience or true improvement in competency requires further investigation.",2018 Jan 23,"['Park, Kyong-Min', 'Park, Kye-Yeung', 'Kim, Nam-Eun', 'Seo, Bong-Kyung', 'Park, Hoon-Ki', 'Hwang, Hwan-Sik']",Korean J Fam Med,,,True
aef9406b4054bc208dbb8735e5803fd25caa3eba,PMC,Economic burden of pneumococcal infections in children under 5 years of age,http://dx.doi.org/10.1080/21645515.2017.1371378,PMC5791583,28922054,CC BY-NC-ND,"The present study aimed to determine the cost of childhood pneumococcal infections under 5 years of age and to provide further data for future health economy studies. Electronic medical records of children diagnosed with meningitis caused by S. pneumoniae and all-cause pneumonia, and acute otitis media (AOM) between January 2013-April 2014 were retrospectively evaluated. Direct costs for the treatments of hospitalized patients (pneumonia and pneumococcal meningitis) including costs of healthcare services consisted of costs of hospital bed, examination, laboratory analyses, scanning methods, consultation, vascular access procedures, and infusion and intravenous treatments. Direct costs for patients (AOM) treated in outpatient setting included constant price paid for the examination and cost of prescribed antibiotics. Indirect costs included cost of work loss of parents and their transportation expenses. Data of 130 children with pneumococcal meningitis (n = 10), pneumonia (n = 53), and AOM (n = 67) were analyzed. The total median cost was €4,060.38 (direct cost: €3,346.38 and indirect cost: €829.18) for meningitis, €835.91 (direct cost: €480.66 and indirect cost: €330.09) for pneumonia, and €117.32 (direct cost: €17.59 and indirect cost: €99.73) for AOM. The medication cost (p = 0.047), indirect cost (p = 0.032), and total cost (p = 0.011) were significantly higher in pneumonia patients aged ≥36 months than those aged <36 months; however, direct cost of AOM were significantly higher in the patients aged <36 months (p = 0.049). Results of the present study revealed that the treatment cost was significantly enhanced for hospitalization and for advanced disease. Thus, preventive actions, mainly vaccination, should be conducted regularly.",2017 Nov 7,"['Ceyhan, Mehmet', 'Ozsurekci, Yasemin', 'Aykac, Kubra', 'Hacibedel, Basak', 'Ozbilgili, Egemen']",Hum Vaccin Immunother,,,True
b3c71d9d7dd9758f8328933f47d7d460bf24c98e,PMC,Efficacy of inactivated variant porcine epidemic diarrhea virus vaccines in growing pigs,http://dx.doi.org/10.7774/cevr.2018.7.1.61,PMC5795046,29399581,CC BY-NC,"PURPOSE: The first aim of this study was to develop a novel inactivated porcine epidemic diarrhea virus (PEDV) vaccine using the recently isolated Korean PEDV QIAP1401 strain and to evaluate its protective efficacy in growing pigs. The second was to determine the optimum adjuvant formulation of the inactivated PEDV vaccine that induces protection against viral challenge. MATERIALS AND METHODS: To generate high titers of infectious PEDV, the QIAP1401 isolate was passaged in Vero cells. The experimental vaccines were prepared from a binary ethyleneimine-inactivated QIAP1401 strain passaged sequentially 70 times (QIAP1401-p70), formulated with four commercial adjuvants, and administered twice intramuscularly to growing pigs. Challenge studies using a virulent homologous strain of PEDV QIAP1401-p11, which was passaged 11 times after isolation, were performed to assess protection against disease progression and viral shedding during the 15-day observation period. The vaccine-induced antibody responses were measured in serum samples collected at predetermined time points by indirect enzyme-linked immunosorbent assay and virus neutralization test. RESULTS: The QIAP1401-p70 strain had 42 amino acid (aa) mutations, including a 25 aa deletion, and was selected as the inactivated PEDV vaccine candidate. Although none of the pigs that received the experimental vaccines were completely protected against subsequent viral challenge, they exhibited a significantly higher immune response than did non-vaccinated control pigs. Among the vaccine groups, the highest antibody responses were observed in the pigs that received an oil-based multiphasic water/oil/water (W/O/W) emulsion adjuvanted vaccine, which delayed the onset of clinical symptoms and viral shedding. CONCLUSION: A novel inactivated PEDV vaccine formulated with a W/O/W emulsion adjuvant was both immunogenic and protective against viral challenge.",2018 Jan 29,"['Lee, Seung Heon', 'Yang, Dong-Kun', 'Kim, Ha-Hyun', 'Cho, In-Soo']",Clin Exp Vaccine Res,,,True
d5fc202cbd1c346056d079c45f0577b767206fc0,PMC,Improving the Hospital Quality of Care during Winter Periods by Optimizing Budget Allocation Between Rotavirus Vaccination and Bed Expansion,http://dx.doi.org/10.1007/s40258-017-0362-6,PMC5797246,29159785,CC BY-NC,"BACKGROUND: During each winter the hospital quality of care (QoC) in pediatric wards decreases due to a surge in pediatric infectious diseases leading to overcrowded units. Bed occupancy rates often surpass the good hospital bed management threshold of 85%, which can result in poor conditions in the workplace. This study explores how QoC-scores could be improved by investing in additional beds and/or better vaccination programs against vaccine-preventable infectious diseases. METHODS: The Cobb–Douglas model was selected to define the improvement in QoC (%) as a function of two strategies (rotavirus vaccination coverage [%] and addition of extra hospital beds [% of existing beds]), allowing improvement-isocurves to be produced. Subsequently, budget minimization was applied to determine the combination of the two strategies needed to reach a given QoC improvement at the lowest cost. Data from Jessa Hospital (Hasselt, Belgium) were chosen as an example. The annual population in the catchment area to be vaccinated was 7000 children; the winter period was 90 days with 34 pediatric beds available. Rotavirus vaccination cost per course was €118.26 and the daily cost of a pediatric bed was €436.53. The target QoC increase was fixed at 50%. The model was first built with baseline parameter values. RESULTS: The model predicted that a combination of 64% vaccine coverage and 39% extra hospital beds (≈ 13 extra beds) in winter would improve QoC-scores by 50% for the minimum budget allocation. CONCLUSION: The model allows determination of the most efficient allocation of the healthcare budget between rotavirus vaccination and bed expansion for improving QoC-scores during the annual epidemic winter seasons.",2018 Nov 20,"['Dort, Thibaut', 'Schecroun, Nadia', 'Standaert, Baudouin']",Appl Health Econ Health Policy,,,True
05cc87a56d714cc75ce393c73f3076d3f8a463b5,PMC,Feline coronavirus antibody titer in cerebrospinal fluid from cats with neurological signs,http://dx.doi.org/10.1292/jvms.17-0399,PMC5797860,29118313,CC BY-NC-ND,"To investigate the utility of cerebrospinal fluid (CSF) anti-feline coronavirus (FCoV) antibody test for diagnosis of feline infectious peritonitis (FIP), the antibody titers were tested in CSF and sera from 271 FIP-suspected neurological cats. CSF antibody was detected in 28 cats, which were divided into 2 groups; 15 with CSF titer of 1:80 or lower and 13 with CSF titer of 1:640 or higher. In the latter group, reciprocal serum titer/reciprocal CSF titer was 8 or lower, which is extremely lower than normal range (256-2048), and FCoV RNA was detected in all of 11 CSF samples assayed by RT-PCR. Our findings indicate that CSF titer of 1:640 or higher may be served as a candidate for the index for diagnosing FIP.",2018 Jan 9,"['SOMA, Takehisa', 'SAITO, Namiko', 'KAWAGUCHI, Masato', 'SASAI, Kazumi']",J Vet Med Sci,,,True
82256b182006e2f9abcd1475c906b290a8daad13,PMC,MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape,http://dx.doi.org/10.1073/pnas.1706928115,PMC5798318,29339515,CC BY-NC-ND,"Convergent evolution dictates that diverse groups of viruses will target both similar and distinct host pathways to manipulate the immune response and improve infection. In this study, we sought to leverage this uneven viral antagonism to identify critical host factors that govern disease outcome. Utilizing a systems-based approach, we examined differential regulation of IFN-γ–dependent genes following infection with robust respiratory viruses including influenza viruses [A/influenza/Vietnam/1203/2004 (H5N1-VN1203) and A/influenza/California/04/2009 (H1N1-CA04)] and coronaviruses [severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV)]. Categorizing by function, we observed down-regulation of gene expression associated with antigen presentation following both H5N1-VN1203 and MERS-CoV infection. Further examination revealed global down-regulation of antigen-presentation gene expression, which was confirmed by proteomics for both H5N1-VN1203 and MERS-CoV infection. Importantly, epigenetic analysis suggested that DNA methylation, rather than histone modification, plays a crucial role in MERS-CoV–mediated antagonism of antigen-presentation gene expression; in contrast, H5N1-VN1203 likely utilizes a combination of epigenetic mechanisms to target antigen presentation. Together, the results indicate a common mechanism utilized by H5N1-VN1203 and MERS-CoV to modulate antigen presentation and the host adaptive immune response.",2018 Jan 30,"['Menachery, Vineet D.', 'Schäfer, Alexandra', 'Burnum-Johnson, Kristin E.', 'Mitchell, Hugh D.', 'Eisfeld, Amie J.', 'Walters, Kevin B.', 'Nicora, Carrie D.', 'Purvine, Samuel O.', 'Casey, Cameron P.', 'Monroe, Matthew E.', 'Weitz, Karl K.', 'Stratton, Kelly G.', 'Webb-Robertson, Bobbie-Jo M.', 'Gralinski, Lisa E.', 'Metz, Thomas O.', 'Smith, Richard D.', 'Waters, Katrina M.', 'Sims, Amy C.', 'Kawaoka, Yoshihiro', 'Baric, Ralph S.']",Proc Natl Acad Sci U S A,,,True
cd91cc69047a0be5fe0816b84a313198751a9df8,PMC,MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape,http://dx.doi.org/10.1073/pnas.1706928115,PMC5798318,29339515,CC BY-NC-ND,"Convergent evolution dictates that diverse groups of viruses will target both similar and distinct host pathways to manipulate the immune response and improve infection. In this study, we sought to leverage this uneven viral antagonism to identify critical host factors that govern disease outcome. Utilizing a systems-based approach, we examined differential regulation of IFN-γ–dependent genes following infection with robust respiratory viruses including influenza viruses [A/influenza/Vietnam/1203/2004 (H5N1-VN1203) and A/influenza/California/04/2009 (H1N1-CA04)] and coronaviruses [severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV)]. Categorizing by function, we observed down-regulation of gene expression associated with antigen presentation following both H5N1-VN1203 and MERS-CoV infection. Further examination revealed global down-regulation of antigen-presentation gene expression, which was confirmed by proteomics for both H5N1-VN1203 and MERS-CoV infection. Importantly, epigenetic analysis suggested that DNA methylation, rather than histone modification, plays a crucial role in MERS-CoV–mediated antagonism of antigen-presentation gene expression; in contrast, H5N1-VN1203 likely utilizes a combination of epigenetic mechanisms to target antigen presentation. Together, the results indicate a common mechanism utilized by H5N1-VN1203 and MERS-CoV to modulate antigen presentation and the host adaptive immune response.",2018 Jan 30,"['Menachery, Vineet D.', 'Schäfer, Alexandra', 'Burnum-Johnson, Kristin E.', 'Mitchell, Hugh D.', 'Eisfeld, Amie J.', 'Walters, Kevin B.', 'Nicora, Carrie D.', 'Purvine, Samuel O.', 'Casey, Cameron P.', 'Monroe, Matthew E.', 'Weitz, Karl K.', 'Stratton, Kelly G.', 'Webb-Robertson, Bobbie-Jo M.', 'Gralinski, Lisa E.', 'Metz, Thomas O.', 'Smith, Richard D.', 'Waters, Katrina M.', 'Sims, Amy C.', 'Kawaoka, Yoshihiro', 'Baric, Ralph S.']",Proc Natl Acad Sci U S A,,,False
d11a76dee8f03c0def1b8b254af658b685252588,PMC,Does Rapid and Sustained Economic Growth Lead to Convergence in Health Resources: The Case of China From 1980 to 2010,http://dx.doi.org/10.1177/0046958016631699,PMC5798700,26895881,CC BY-NC,"China’s rapid and sustained economic growth offers an opportunity to ask whether the advantages of growth diffuse throughout an economy, or remain localized in areas where the growth has been the greatest. A critical policy area in China has been the health system, and health inequality has become an issue that has led the government to broaden national health insurance programs. This study investigates whether health system resources and performance have converged over the past 30 years across China’s 31 provinces. To examine geographic variation of health system resources and performance at the provincial level, we measure the degree of sigma convergence and beta convergence in indicators of health system resources (structure), health services utilization (process), and outcome. All data are from officially published sources: the China Health Statistics Year Book and the China Statistics Year Book. Sigma convergence is found for resource indicators, whereas it is not observed for either process or outcome indicators, indicating that disparities only narrowed in health system resources. Beta convergence is found in most indicators, except for 2 procedure indicators, reflecting that provinces with poorer resources were catching up. Convergence found in this study probably reflects the mixed outcome of government input, and market forces. Thus, left alone, the equitable distribution of health care resources may not occur naturally during a period of economic growth. Governmental and societal efforts are needed to reduce geographic health variation and promote health equity.",2016 Feb 19,"['Liang, Di', 'Zhang, Donglan', 'Huang, Jiayan', 'Schweitzer, Stuart']",Inquiry,,,True
a46ec82f209bf008fd96e99c212ef8f0d4ae33b5,PMC,Organization and Finance of China’s Health Sector: Historical Antecedents for Macroeconomic Structural Adjustment,http://dx.doi.org/10.1177/0046958015620175,PMC5798748,26831625,CC BY-NC,"China has exploded onto the world economy over the past few decades and is undergoing rapid transformation toward relatively more services. The health sector is an important part of this transition. This article provides a historical account of the development of health care in China since 1949. It also focuses on health insurance and macroeconomic structural adjustment to less saving and more consumption. In particular, the question of how health insurance impacts precautionary savings is considered. Multivariate analysis using data from 1990 to 2012 is employed. The household savings rate is the dependent variable in 3 models segmented for rural and urban populations. Independent variables include out-of-pocket health expenditures, health insurance payouts, housing expenditure, education expenditure, and consumption as a share of gross domestic product (GDP). Out-of-pocket health expenditures were positively correlated with household savings rates. But health insurance remains weak, and increased payouts by health insurers have not been associated with lower levels of household savings so far. Housing was positively correlated, whereas education had a negative association with savings rates. This latter finding was unexpected. Perhaps education is perceived as investment and a substitute for savings. China’s shift toward a more service-oriented economy includes growing dependence on the health sector. Better health insurance is an important part of this evolution. The organization and finance of health care is integrally linked with macroeconomic policy in an environment constrained by prevailing institutional convention. Problems of agency relationships, professional hegemony, and special interest politics feature prominently, as they do elsewhere. China also has a dual approach to medicine relying heavily on providers of traditional Chinese medicine. Both of these segments will take part in China’s evolution, adding another layer of complexity to policy.",2016 Jan 31,"['Li, Hui', 'Hilsenrath, Peter']",Inquiry,,,True
0c83fb7b5413cd36d8ca958f15e7640636c8e730,PMC,Isolation and characterization of a new porcine epidemic diarrhea virus variant that occurred in Korea in 2014,http://dx.doi.org/10.4142/jvs.2018.19.1.71,PMC5799402,28693308,CC BY-NC,"Outbreaks of porcine epidemic diarrhea (PED) have resulted in significant economic losses in the swine industry, and another PED outbreak occurred in 2014 in Korea. Isolating and culturing PED virus (PEDV) allow investigations into its pathogenesis and the development of vaccines and diagnostic assays. In this study, we successfully isolated two PEDV isolates (QIAP1401 and QIAP1402) from naturally infected piglets at Jeju-do, Korea. Viral propagation was confirmed in Vero cells based on cytopathic effect, immunofluorescence assay, reverse transcription-polymerase chain reaction, and electron microscopic analyses. The QIAP401 isolate propagated well in Vero cells for 70 passages, with titers of 10(6.5) to 10(7.0) 50% tissue culture infectious dose/mL, which increased gradually with passaging. The nucleotide and amino acid sequences of the QIAP1401 isolate were determined and compared with those of other PEDV isolates. The QIAP1401 isolate was determined to be closely related to the USA/Minnesota271/2014 strain (> 99.9% nucleotide similarity) that was isolated in the USA in 2014. Phylogenetic analysis based on several PEDV genes suggested that a new PEDV variant is circulating in the Korean swine industry, with 93.08% similarity to the SM98 strain isolated in 1998. In addition, the QIAP1401 strain showed strong virulence in 3-day-old piglets and 11-week-old growing pigs.",2018 Jan 23,"['Yang, Dong-Kun', 'Kim, Ha-Hyun', 'Lee, Seung-Heon', 'Yoon, Soon-Seek', 'Park, Jung-Won', 'Cho, In-Soo']",J Vet Sci,,,True
2e45740f4d2001e92d14d657feef0191f769cb61,PMC,"Incidence, Etiology, and Outcomes of Community-Acquired Pneumonia: A Population-Based Study",http://dx.doi.org/10.1093/ofid/ofy010,PMC5804852,29479548,CC BY-NC-ND,"BACKGROUND: The microbial etiology of community-acquired pneumonia (CAP) is often unclear in clinical practice, and previous studies have produced variable results. Population-based studies examining etiology and incidence are lacking. This study examined the incidence and etiology of CAP requiring hospitalization in a population-based cohort as well as risk factors and outcomes for specific etiologies. METHODS: Consecutive admissions due to CAP in Reykjavik, Iceland were studied. Etiologic testing was performed with cultures, urine-antigen detection, and polymerase chain reaction analysis of airway samples. Outcomes were length of stay, intensive care unit admission, assisted ventilation, and mortality. RESULTS: The inclusion rate was 95%. The incidence of CAP requiring hospitalization was 20.6 cases per 10000 adults/year. A potential pathogen was detected in 52% (164 of 310) of admissions and in 74% (43 of 58) with complete sample sets. Streptococcuspneumoniae was the most common pathogen (61 of 310, 20%; incidence: 4.1/10000). Viruses were identified in 15% (47 of 310; incidence: 3.1/10000), Mycoplasmapneumoniae were identified in 12% (36 of 310; incidence: 2.4/10000), and multiple pathogens were identified in 10% (30 of 310; incidence: 2.0/10000). Recent antimicrobial therapy was associated with increased detection of M pneumoniae (P < .001), whereas a lack of recent antimicrobial therapy was associated with increased detection of S pneumoniae (P = .02). Symptoms and outcomes were similar irrespective of microbial etiology. CONCLUSIONS: Pneumococci, M pneumoniae, and viruses are the most common pathogens associated with CAP requiring hospital admission, and they all have a similar incidence that increases with age. Symptoms do not correlate with specific agents, and outcomes are similar irrespective of pathogens identified.",2018 Feb 8,"['Bjarnason, Agnar', 'Westin, Johan', 'Lindh, Magnus', 'Andersson, Lars-Magnus', 'Kristinsson, Karl G', 'Löve, Arthur', 'Baldursson, Olafur', 'Gottfredsson, Magnus']",Open Forum Infect Dis,,,True
129fe5d1e963bc655146edf42a382819deca0ce6,PMC,The European Respiratory Society course on acute respiratory pandemics: how to plan for and manage them,http://dx.doi.org/10.1183/23120541.00156-2017,PMC5809820,29450202,CC BY-NC,Learn about the @ERStalk course on acute respiratory pandemics http://ow.ly/XGe430i7743,2018 Feb 13,"['Adeoti, Adekunle Olatayo', 'Marbus, Sierk']",ERJ Open Res,,,True
6bbd4c83266579a2afbe995cf64f3200d4d4cb7b,PMC,Genetic diversity and cross-species transmission of kobuviruses in Vietnam,http://dx.doi.org/10.1093/ve/vey002,PMC5810437,29449965,CC BY-NC,"Cross-species transmission of viruses poses a sustained threat to public health. Due to increased contact between humans and other animal species the possibility exists for cross-species transmissions and ensuing disease outbreaks. By using conventional PCR amplification and next generation sequencing, we obtained 130 partial or full genome kobuvirus sequences from humans in a sentinel cohort in Vietnam and various mammalian hosts including bats, rodents, pigs, cats, and civets. The evolution of kobuviruses in different hosts was analysed using Bayesian phylogenetic methods. We estimated and compared time of origin of kobuviruses in different host orders; we also examined the cross-species transmission of kobuviruses within the same host order and between different host orders. Our data provide new knowledge of rodent and bat kobuviruses, which are most closely related to human kobuviruses. The novel bat kobuviruses isolated from bat roosts in Southern Vietnam were genetically distinct from previously described bat kobuviruses, but closely related to kobuviruses found in rodents. We additionally found evidence of frequent cross-species transmissions of kobuviruses within rodents. Overall, our phylogenetic analyses reveal multiple cross-species transmissions both within and among mammalian species, which increases our understanding of kobuviruses genetic diversity and the complexity of their evolutionary history.",2018 Feb 13,"['Lu, Lu', 'Van Dung, Nguyen', 'Ivens, Alasdair', 'Bogaardt, Carlijn', 'O’Toole, Aine', 'Bryant, Juliet E', 'Carrique-Mas, Juan', 'Van Cuong, Nguyen', 'Anh, Pham Hong', 'Rabaa, Maia A', 'Tue, Ngo Tri', 'Thwaites, Guy E', 'Baker, Stephen', 'Simmonds, Peter', 'Woolhouse, Mark Ej', None]",Virus Evol,,,True
1213b69feb045ffa00557e877b1b99e4855b386c,PMC,Genetic diversity and cross-species transmission of kobuviruses in Vietnam,http://dx.doi.org/10.1093/ve/vey002,PMC5810437,29449965,CC BY-NC,"Cross-species transmission of viruses poses a sustained threat to public health. Due to increased contact between humans and other animal species the possibility exists for cross-species transmissions and ensuing disease outbreaks. By using conventional PCR amplification and next generation sequencing, we obtained 130 partial or full genome kobuvirus sequences from humans in a sentinel cohort in Vietnam and various mammalian hosts including bats, rodents, pigs, cats, and civets. The evolution of kobuviruses in different hosts was analysed using Bayesian phylogenetic methods. We estimated and compared time of origin of kobuviruses in different host orders; we also examined the cross-species transmission of kobuviruses within the same host order and between different host orders. Our data provide new knowledge of rodent and bat kobuviruses, which are most closely related to human kobuviruses. The novel bat kobuviruses isolated from bat roosts in Southern Vietnam were genetically distinct from previously described bat kobuviruses, but closely related to kobuviruses found in rodents. We additionally found evidence of frequent cross-species transmissions of kobuviruses within rodents. Overall, our phylogenetic analyses reveal multiple cross-species transmissions both within and among mammalian species, which increases our understanding of kobuviruses genetic diversity and the complexity of their evolutionary history.",2018 Feb 13,"['Lu, Lu', 'Van Dung, Nguyen', 'Ivens, Alasdair', 'Bogaardt, Carlijn', 'O’Toole, Aine', 'Bryant, Juliet E', 'Carrique-Mas, Juan', 'Van Cuong, Nguyen', 'Anh, Pham Hong', 'Rabaa, Maia A', 'Tue, Ngo Tri', 'Thwaites, Guy E', 'Baker, Stephen', 'Simmonds, Peter', 'Woolhouse, Mark Ej', None]",Virus Evol,,,False
a2c2196aecd2142d5881124b7cd8ff252581c784,PMC,"Heparin‐binding protein, lysozyme, and inflammatory cytokines in bronchoalveolar lavage fluid as diagnostic tools for pulmonary infection in lung transplanted patients",http://dx.doi.org/10.1111/ajt.14458,PMC5813223,28787761,CC BY-NC,"Pulmonary infection is a common complication after lung transplantation, and early detection is crucial for outcome. However, the condition can be clinically difficult to diagnose and to distinguish from rejection. The aim of this prospective study was to evaluate heparin‐binding protein (HBP), lysozyme, and the cytokines interleukin (IL)‐1β, IL‐6, IL‐8, IL‐10 and tumor necrosis factor (TNF) in bronchoalveolar lavage fluid (BALF) as potential biomarkers for pulmonary infection in lung‐transplanted patients. One hundred thirteen BALF samples from 29 lung transplant recipients were collected at routine scheduled bronchoscopies at 3 and 6 months, or on clinical indication. Samples were classified into no, possible, probable, or definite infection at the time of sampling. Rejection was defined by biopsy results. HBP, lysozyme, and cytokines were analyzed in BALF and correlated to likelihood of infection and rejection. All biomarkers were significantly increased in BALF during infection, whereas patients with rejection presented low levels that were comparable to noninfection samples. HBP, IL‐1β, and IL‐8 were the best diagnostic markers of infection with area under the receiver‐operating characteristic curve values of 0.88, 0.91, and 0.90, respectively. In conclusion, HBP, IL‐1β, and IL‐8 could be useful diagnostic markers of pulmonary infection in lung‐transplanted patients.",2018 Feb 15,"['Stjärne Aspelund, Anna', 'Hammarström, Helena', 'Inghammar, Malin', 'Larsson, Hillevi', 'Hansson, Lennart', 'Christensson, Bertil', 'Påhlman, Lisa I.']",Am J Transplant,,,True
01bc7fe59fc7feb0e3d23c716aa23a694a4362a2,PMC,Outpatient Antibiotic Stewardship: A Growing Frontier—Combining Myxovirus Resistance Protein A With Other Biomarkers to Improve Antibiotic Use,http://dx.doi.org/10.1093/ofid/ofy024,PMC5815119,29479553,CC BY-NC-ND,"BACKGROUND: The majority of oral antibiotics are prescribed in outpatient primary and urgent care clinics for acute respiratory infections. Effective antibiotic stewardship must include proper prescribing for outpatients as well as for those in a hospital or long-term care facility. METHODS: Major databases, including MEDLINE and the Cochrane Library, were searched for prospective human clinical studies, including children and/or adults published between January 1966 and November 2017 that evaluated Myxovirus resistance protein A (MxA) as a biomarker for diagnosing viral infections as well as both C-reactive protein (CRP) and procalcitonin (PCT) as potential biomarkers for identifying and differentiating true bacterial upper respiratory infection (URI) from colonization. RESULTS: Ten prospective human studies, totaling 1683 patients, were identified that evaluated MxA as a viral biomarker in children and/or adults. Both systematic review articles, meta-analyses, and randomized controlled clinical trials that examined CRP and/or PCT as a biomarker for identifying clinically significant bacterial infections and supporting antibiotic stewardship were identified. CONCLUSIONS: Quick and accurate differentiation between a viral and bacterial respiratory infection is critical to effectively combat antibiotic misuse. MxA expression in peripheral blood is a highly specific marker for viral infection. Combining MxA with other inflammatory biomarkers to test for respiratory infections offers enhanced sensitivity and specificity, forming an excellent tool for antibiotic stewardship in the outpatient setting.",2018 Feb 15,"['Joseph, Patrick', 'Godofsky, Eliot']",Open Forum Infect Dis,,,True
b2ff10bcb290b39b39f3f8a2206555baad677a5d,PMC,Viral and Bacterial Etiologies of Acute Respiratory Infections Among Children Under 5 Years in Senegal,http://dx.doi.org/10.1177/1178636118758651,PMC5815418,29467579,CC BY-NC,"Acute respiratory infections (ARIs) are the leading cause of infectious disease–related morbidity, hospitalization, and morbidity among children worldwide. This study aimed to assess the viral and bacterial causes of ARI morbidity and mortality in children under 5 years in Senegal. Nasopharyngeal samples were collected from children under 5 years who had ARI. Viruses and bacteria were identified using multiplex real-time reverse transcription-polymerase chain reaction and conventional biochemical techniques, respectively. Adenovirus was the most prevalent virus (50%; n = 81), followed by influenza virus (45.68%, n = 74), rhinovirus (40.12%; n = 65), enterovirus (25.31%; n = 41), and respiratory syncytial virus (16.05%; n = 26), whereas Streptococcus pneumoniae (17%; n = 29), Moraxella catarrhalis (15.43%; n = 25), and Haemophilus influenzae (8.02%; n = 13) were the most commonly isolated bacteria. Virus pathogens seem more likely to be more prevalent in our settings and were often associated with bacteria and S. pneumoniae (6%; 16) coinfection.",2018 Feb 13,"['Assane, Dieng', 'Makhtar, Camara', 'Abdoulaye, Diop', 'Amary, Fall', 'Djibril, Boiro', 'Amadou, Diop', 'Niokhor, Diouf Jean Baptiste', 'Amadou, Diop', 'Cheikh, Loucoubar', 'Ndongo, Dia', 'Mbayame, Niang', 'Lamine, Fall', 'Bouh, Boye Cheikh Saad']",Microbiol Insights,,,True
9a5d753bbf216af4c354c0aa460a2a127c1da0a8,PMC,Impact of a Hypothetical Infectious Disease Outbreak on US Exports and Export-Based Jobs,http://dx.doi.org/10.1089/hs.2017.0052,PMC5815448,29405775,CC BY-NC,"We estimated the impact on the US export economy of an illustrative infectious disease outbreak scenario in Southeast Asia that has 3 stages starting in 1 country and, if uncontained, spreads to 9 countries. We used 2014-2016 West Africa Ebola epidemic–related World Bank estimates of 3.3% and 16.1% reductions in gross domestic product (GDP). We also used US Department of Commerce job data to calculate export-related jobs at risk to any outbreak-related disruption in US exports. Assuming a direct correlation between GDP reductions and reduced demand for US exports, we estimated that the illustrative outbreak would cost from approximately $13 million to approximately $64 million (1 country) to $8 billion to $41 billion (9 countries) and place 1,500 to almost 1.4 million export-related US jobs at risk. Our analysis illustrates how global health security is enhanced, and the US economy is protected, when public health threats are rapidly detected and contained at their source.",2018 Feb 1,"['Bambery, Zoe', 'Cassell, Cynthia H.', 'Bunnell, Rebecca E.', 'Roy, Kakoli', 'Ahmed, Zara', 'Payne, Rebecca L.', 'Meltzer, Martin I.']",Health Secur,,,True
012dd7094e614d0f0e9e1da5cc56a3fe225f961c,PMC,Impact of a Hypothetical Infectious Disease Outbreak on US Exports and Export-Based Jobs,http://dx.doi.org/10.1089/hs.2017.0052,PMC5815448,29405775,CC BY-NC,"We estimated the impact on the US export economy of an illustrative infectious disease outbreak scenario in Southeast Asia that has 3 stages starting in 1 country and, if uncontained, spreads to 9 countries. We used 2014-2016 West Africa Ebola epidemic–related World Bank estimates of 3.3% and 16.1% reductions in gross domestic product (GDP). We also used US Department of Commerce job data to calculate export-related jobs at risk to any outbreak-related disruption in US exports. Assuming a direct correlation between GDP reductions and reduced demand for US exports, we estimated that the illustrative outbreak would cost from approximately $13 million to approximately $64 million (1 country) to $8 billion to $41 billion (9 countries) and place 1,500 to almost 1.4 million export-related US jobs at risk. Our analysis illustrates how global health security is enhanced, and the US economy is protected, when public health threats are rapidly detected and contained at their source.",2018 Feb 1,"['Bambery, Zoe', 'Cassell, Cynthia H.', 'Bunnell, Rebecca E.', 'Roy, Kakoli', 'Ahmed, Zara', 'Payne, Rebecca L.', 'Meltzer, Martin I.']",Health Secur,,,False
1d5cd90e386f1ac643f681af47eadb16f73b4b41,PMC,Impact of a Hypothetical Infectious Disease Outbreak on US Exports and Export-Based Jobs,http://dx.doi.org/10.1089/hs.2017.0052,PMC5815448,29405775,CC BY-NC,"We estimated the impact on the US export economy of an illustrative infectious disease outbreak scenario in Southeast Asia that has 3 stages starting in 1 country and, if uncontained, spreads to 9 countries. We used 2014-2016 West Africa Ebola epidemic–related World Bank estimates of 3.3% and 16.1% reductions in gross domestic product (GDP). We also used US Department of Commerce job data to calculate export-related jobs at risk to any outbreak-related disruption in US exports. Assuming a direct correlation between GDP reductions and reduced demand for US exports, we estimated that the illustrative outbreak would cost from approximately $13 million to approximately $64 million (1 country) to $8 billion to $41 billion (9 countries) and place 1,500 to almost 1.4 million export-related US jobs at risk. Our analysis illustrates how global health security is enhanced, and the US economy is protected, when public health threats are rapidly detected and contained at their source.",2018 Feb 1,"['Bambery, Zoe', 'Cassell, Cynthia H.', 'Bunnell, Rebecca E.', 'Roy, Kakoli', 'Ahmed, Zara', 'Payne, Rebecca L.', 'Meltzer, Martin I.']",Health Secur,,,False
ed21f99a11ebb65e8c3a6fb8d00b7141011916b0,PMC,Paediatric Virology and its interaction between basic science and clinical practice (Review),http://dx.doi.org/10.3892/ijmm.2018.3364,PMC5819919,29328393,CC BY-NC-ND,"The 3rd Workshop on Paediatric Virology, which took place on October 7th, 2017 in Athens, Greece, highlighted the role of breast feeding in the prevention of viral infections during the first years of life. Moreover, it focused on the long-term outcomes of respiratory syncytial virus and rhinovirus infections in prematurely born infants and emphasised the necessity for the development of relevant preventative strategies. Other topics that were covered included the vaccination policy in relation to the migration crisis, mother-to-child transmission of hepatitis B and C viruses, vaccination against human papilloma viruses in boys and advances on intranasal live-attenuated vaccination against influenza. Emphasis was also given to the role of probiotics in the management of viral infections in childhood, the potential association between viral infections and the pathogenesis of asthma, fetal and neonatal brain imaging and the paediatric intensive care of children with central nervous system viral infections. Moreover, an interesting overview of the viral causes of perinatal mortality in ancient Greece was given, where recent archaeological findings from the Athenian Agora’s bone well were presented. Finally, different continuing medical educational options in Paediatric Virology were analysed and evaluated. The present review provides an update of the key topics discussed during the workshop.",2018 Mar 4,"['Mammas, Ioannis N.', 'Greenough, Anne', 'Theodoridou, Maria', 'Kramvis, Anna', 'Rusan, Maria', 'Melidou, Angeliki', 'Korovessi, Paraskevi', 'Papaioannou, Georgia', 'Papatheodoropoulou, Alexia', 'Koutsaftiki, Chryssie', 'Liston, Maria', 'Sourvinos, George', 'Spandidos, Demetrios A.']",Int J Mol Med,,,True
0d0ca66887cfd2b3a09f5205cdcbaa4479f17337,PMC,Successive occurrence of recombinant infectious bronchitis virus strains in restricted area of Middle East,http://dx.doi.org/10.1093/ve/vew021,PMC5822880,29492274,CC BY-NC,"Routine molecular diagnostic testing by our laboratory, based on using a primer pair with conservative binding sites on the spike glycoprotein coding sequence, has indicated the recurring of a unique phylogenetic cluster of chicken infectious bronchitis viruses (IBV) in the Middle East since 2010. The nearly full-length S1 subunit of the spike gene phylogeny of selected strains, however, split up this grouping, suggesting potential recombination in the S1 gene. In order to clarify this, various bioinformatic analyses of the strains were carried out, which confirmed this supposition. Two patterns of recombination were found among the strains, one of which could also be identified in GenBank-deposited IBV sequences from the region. These findings demonstrate that IBV strains of different recombinant patterns occur simultaneously in the same geographic region and could circulate for an extended period of time, thus contributing to the knowledge on IBV evolution.",2016 Aug 3,"['Kiss, István', 'Mató, Tamás', 'Homonnay, Zalán', 'Tatár-Kis, Tímea', 'Palya, Vilmos']",Virus Evol,,,True
6b881730788724e674806854f0c20fec32ee9d96,PMC,Challenges in the analysis of viral metagenomes,http://dx.doi.org/10.1093/ve/vew022,PMC5822887,29492275,CC BY-NC,"Genome sequencing technologies continue to develop with remarkable pace, yet analytical approaches for reconstructing and classifying viral genomes from mixed samples remain limited in their performance and usability. Existing solutions generally target expert users and often have unclear scope, making it challenging to critically evaluate their performance. There is a growing need for intuitive analytical tooling for researchers lacking specialist computing expertise and that is applicable in diverse experimental circumstances. Notable technical challenges have impeded progress; for example, fragments of viral genomes are typically orders of magnitude less abundant than those of host, bacteria, and/or other organisms in clinical and environmental metagenomes; observed viral genomes often deviate considerably from reference genomes demanding use of exhaustive alignment approaches; high intrapopulation viral diversity can lead to ambiguous sequence reconstruction; and finally, the relatively few documented viral reference genomes compared to the estimated number of distinct viral taxa renders classification problematic. Various software tools have been developed to accommodate the unique challenges and use cases associated with characterizing viral sequences; however, the quality of these tools varies, and their use often necessitates computing expertise or access to powerful computers, thus limiting their usefulness to many researchers. In this review, we consider the general and application-specific challenges posed by viral sequencing and analysis, outline the landscape of available tools and methodologies, and propose ways of overcoming the current barriers to effective analysis.",2016 Aug 3,"['Rose, Rebecca', 'Constantinides, Bede', 'Tapinos, Avraam', 'Robertson, David L', 'Prosperi, Mattia']",Virus Evol,,,True
3c3a1e707eaf3efae5ae22cced7d4850ffc1f587,PMC,Systems Biology-Based Platforms to Accelerate Research of Emerging Infectious Diseases,http://dx.doi.org/10.3349/ymj.2018.59.2.176,PMC5823818,29436184,CC BY-NC,"Emerging infectious diseases (EIDs) pose a major threat to public health and security. Given the dynamic nature and significant impact of EIDs, the most effective way to prevent and protect against them is to develop vaccines in advance. Systems biology approaches provide an integrative way to understand the complex immune response to pathogens. They can lead to a greater understanding of EID pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner. In recent years, advances in high throughput technologies have enabled researchers to successfully apply systems biology methods to analyze immune responses to a variety of pathogens and vaccines. Despite recent advances, computational and biological challenges impede wider application of systems biology approaches. This review highlights recent advances in the fields of systems immunology and vaccinology, and presents ways that systems biology-based platforms can be applied to accelerate a deeper understanding of the molecular mechanisms of immunity against EIDs.",2018 Mar 1,"['Oh, Soo-Jin', 'Choi, Young-Ki', 'Shin, Ok Sarah']",Yonsei Med J,,,True
c436139975d97ef929b5d8452595de40bda0c11c,PMC,A Randomized Study of Immune Plasma for the Treatment of Severe Influenza,http://dx.doi.org/10.1016/S2213-2600(17)30174-1,PMC5828518,28522352,CC BY-NC-ND,"BACKGROUND: Influenza causes significant morbidity and mortality despite currently available treatments. Anecdotal reports suggest plasma with high antibody titers towards influenza may be of benefit in the treatment of severe influenza. METHODS: We conducted a randomized, open-label, multicenter phase 2 trial at 29 academic medical centers in the United States to assess the safety and efficacy of anti-influenza plasma with hemagglutination inhibition (HAI) antibody titers of ≥ 1:80 to the infecting strain. Hospitalized children and adults (including pregnant women) with severe influenza A or B (defined as hypoxia or tachypnea) were randomly assigned to receive either 2 units (or pediatric equivalent) of anti-influenza plasma plus standard care (P+S), versus standard care alone (S), and were followed for 28 days. The primary endpoint was time to normalization of patients’ respiratory status (respiratory rate of ≤ 20 for adults or age defined thresholds of 20–38 for children), and a room air saturation of oxygen ≥ 93%. ClinicalTrials.gov Identifier: NCT01052480 FINDINGS: Between January 13, 2011 and March 2, 2015, 113 participants were screened, and 98 were randomized. Of the participants with confirmed influenza, 28 of 42 (67%) of P+S participants normalized their respiratory status by Day 28, as compared to 24 of 45 (53%) of S participants (p=0·069). The estimated hazard ratio comparing P+S to S was 1·71 (95% CI: 0·96 to 3·06). Six participants died, 1 (2%) and 5 (10%) from the P+S and S arms respectively (p=0·093). P+S participants had non-significant reductions in days in hospital (median 6 vs. 11 days, p=0·13) and days on mechanical ventilation (median 0 vs. 3 days, p=0·14), and significantly improved clinical status at Day 7 (p=0·020). Fewer P+S participants experienced SAEs compared to S recipients (20% vs. 38%, p= 0·041), the most frequent of which were acute respiratory distress syndrome (1 [2%] vs 2 [4%]) and stroke (1 [2%] vs 2 [4%]). INTERPRETATION: Results from this Phase II randomized trial of immune plasma for the treatment of severe influenza provides support for a possible benefit of immunotherapy across the primary and secondary endpoints. A Phase III randomized trial is now underway to further evaluate this intervention.",2017 Jun 15,"['Beigel, John H.', 'Tebas, Pablo', 'Elie-Turenne, Marie-Carmelle', 'Bajwa, Ednan', 'Bell, Todd E.', 'Cairns, Charles B.', 'Shoham, Shmuel', 'Deville, Jaime G.', 'Feucht, Eric', 'Feinberg, Judith', 'Luke, Thomas', 'Raviprakash, Kanakatte', 'Danko, Janine', 'O’Neil, Dorothy', 'Metcalf, Julia A.', 'King, Karen', 'Burgess, Timothy H.', 'Aga, Evgenia', 'Lane, H. Clifford', 'Hughes, Michael D.', 'Davey, Richard T.']",Lancet Respir Med,,,True
a78e31beaf8becf35eacaa356661ea99c97e8652,PMC,"Global Influenza Hospital-based Surveillance Network (GIHSN): results of surveillance of influenza and other respiratory viruses in hospitalised patients in Brazil, 2015",http://dx.doi.org/10.1136/bmjopen-2017-017603,PMC5829850,29449287,CC BY-NC,"BACKGROUND: Influenza-like illness occurs annually worldwide, with peak timing and severity varying seasonally, resulting in significant annual mortality. OBJECTIVES: There were three objectives: (1) to describe the epidemiological and clinical features of hospitalised patients with severe acute respiratory infection caused by influenza and other respiratory viruses (ORVs); (2) to report the influenza seasonality in the region and (3) to correlate findings of influenza circulation and immunisation time in Brazil. PATIENTS/METHODS: This study took place in three Brazilian hospitals located in cities with different climatic conditions (Curitiba (south), Rio de Janeiro (south-east) and Fortaleza (north-east)). Patients presenting with an acute process with indication for admission consisting of a predefined set of conditions potentially associated with recent influenza infection were enrolled. RESULTS: We screened 1666 patients, with 595 meeting the inclusion criteria. Influenza viruses and ORVs were detected in 6.5% and 59% of patients, respectively. Influenza-positive cases fell into the severe spectrum as compared with those with ORVs (30% vs 11%), but without any difference in mortality rates. Epidemiological results revealed variations in the peak time of influenza infections between north-east (Fortaleza) and south (Curitiba) Brazil, basically following the rain period of each region. In north-east Brazil, viral circulation was prevalent in the first 4 months of the year, indicating that the vaccination campaign occurred in a postseasonal period, possibly explaining the low effectiveness. CONCLUSIONS: The active-surveillance model is a valuable tool for investigating respiratory virus impact on hospitalised patients, with influenza-infection monitoring enabling implementation of adequate preventive measures.",2018 Feb 15,"['Raboni, Sonia M', 'Moura, Fernanda EA', 'Caetano, Braulia C', 'Avanzi, Valéria M', 'Pereira, Luciane A', 'Nogueira, Meri B', 'Vidal, Luine R', 'Tavares, Isabel CF', 'Pradel, Florence K', 'Picot, Valentina S', 'Puig-Barbera, Joan', 'Siqueira, Marilda M']",BMJ Open,,,True
99da54318cd9e891d43f15d7b96365e2a2e9740d,PMC,"Global Influenza Hospital-based Surveillance Network (GIHSN): results of surveillance of influenza and other respiratory viruses in hospitalised patients in Brazil, 2015",http://dx.doi.org/10.1136/bmjopen-2017-017603,PMC5829850,29449287,CC BY-NC,"BACKGROUND: Influenza-like illness occurs annually worldwide, with peak timing and severity varying seasonally, resulting in significant annual mortality. OBJECTIVES: There were three objectives: (1) to describe the epidemiological and clinical features of hospitalised patients with severe acute respiratory infection caused by influenza and other respiratory viruses (ORVs); (2) to report the influenza seasonality in the region and (3) to correlate findings of influenza circulation and immunisation time in Brazil. PATIENTS/METHODS: This study took place in three Brazilian hospitals located in cities with different climatic conditions (Curitiba (south), Rio de Janeiro (south-east) and Fortaleza (north-east)). Patients presenting with an acute process with indication for admission consisting of a predefined set of conditions potentially associated with recent influenza infection were enrolled. RESULTS: We screened 1666 patients, with 595 meeting the inclusion criteria. Influenza viruses and ORVs were detected in 6.5% and 59% of patients, respectively. Influenza-positive cases fell into the severe spectrum as compared with those with ORVs (30% vs 11%), but without any difference in mortality rates. Epidemiological results revealed variations in the peak time of influenza infections between north-east (Fortaleza) and south (Curitiba) Brazil, basically following the rain period of each region. In north-east Brazil, viral circulation was prevalent in the first 4 months of the year, indicating that the vaccination campaign occurred in a postseasonal period, possibly explaining the low effectiveness. CONCLUSIONS: The active-surveillance model is a valuable tool for investigating respiratory virus impact on hospitalised patients, with influenza-infection monitoring enabling implementation of adequate preventive measures.",2018 Feb 15,"['Raboni, Sonia M', 'Moura, Fernanda EA', 'Caetano, Braulia C', 'Avanzi, Valéria M', 'Pereira, Luciane A', 'Nogueira, Meri B', 'Vidal, Luine R', 'Tavares, Isabel CF', 'Pradel, Florence K', 'Picot, Valentina S', 'Puig-Barbera, Joan', 'Siqueira, Marilda M']",BMJ Open,,,True
231ba154ea0d9a668c5c5e7e5732c4f223608f6d,PMC,"Global Influenza Hospital-based Surveillance Network (GIHSN): results of surveillance of influenza and other respiratory viruses in hospitalised patients in Brazil, 2015",http://dx.doi.org/10.1136/bmjopen-2017-017603,PMC5829850,29449287,CC BY-NC,"BACKGROUND: Influenza-like illness occurs annually worldwide, with peak timing and severity varying seasonally, resulting in significant annual mortality. OBJECTIVES: There were three objectives: (1) to describe the epidemiological and clinical features of hospitalised patients with severe acute respiratory infection caused by influenza and other respiratory viruses (ORVs); (2) to report the influenza seasonality in the region and (3) to correlate findings of influenza circulation and immunisation time in Brazil. PATIENTS/METHODS: This study took place in three Brazilian hospitals located in cities with different climatic conditions (Curitiba (south), Rio de Janeiro (south-east) and Fortaleza (north-east)). Patients presenting with an acute process with indication for admission consisting of a predefined set of conditions potentially associated with recent influenza infection were enrolled. RESULTS: We screened 1666 patients, with 595 meeting the inclusion criteria. Influenza viruses and ORVs were detected in 6.5% and 59% of patients, respectively. Influenza-positive cases fell into the severe spectrum as compared with those with ORVs (30% vs 11%), but without any difference in mortality rates. Epidemiological results revealed variations in the peak time of influenza infections between north-east (Fortaleza) and south (Curitiba) Brazil, basically following the rain period of each region. In north-east Brazil, viral circulation was prevalent in the first 4 months of the year, indicating that the vaccination campaign occurred in a postseasonal period, possibly explaining the low effectiveness. CONCLUSIONS: The active-surveillance model is a valuable tool for investigating respiratory virus impact on hospitalised patients, with influenza-infection monitoring enabling implementation of adequate preventive measures.",2018 Feb 15,"['Raboni, Sonia M', 'Moura, Fernanda EA', 'Caetano, Braulia C', 'Avanzi, Valéria M', 'Pereira, Luciane A', 'Nogueira, Meri B', 'Vidal, Luine R', 'Tavares, Isabel CF', 'Pradel, Florence K', 'Picot, Valentina S', 'Puig-Barbera, Joan', 'Siqueira, Marilda M']",BMJ Open,,,True
d43c9028fc460b667d7b8e54c16f0a85de6f3c4d,PMC,Association of common comorbidities with osteonecrosis: a nationwide population-based case–control study in Denmark,http://dx.doi.org/10.1136/bmjopen-2017-020680,PMC5829903,29439082,CC BY-NC,"OBJECTIVE: To examine recent time trends in the incidence of osteonecrosis (ON) in Denmark and to investigate different common comorbidities association with ON in a population-based setting. METHODS: Using Danish medical databases, we included all patients with a first-time hospital diagnosis of ON during 1995–2012. Each ON case was matched with 10 randomly selected population control subjects from general population. For all participants, we obtained a complete hospital history of comorbidities included in the CharlsonComorbidity Index 5 years preceding the inclusion date. RESULTS: 4107 ON cases and 41 063 controls were included. The incidence of ON increased from 3.9 in 1995 to 5.5 in 2012 per 100 000 inhabitants. Solid cancer was the most common comorbidity, associated with an adjusted OR (aOR) for ON of 2.0 (95% CI 1.7 to 2.2). For advanced metastatic cancer, leukaemia and lymphoma, aORs of ON were 3.4 (95% CI 2.5 to 4.5), 4.3 (95% CI 2.7 to 7.0) and 5.8 (95% CI 4.3 to 7.8), respectively. Among other chronic conditions, aORs were 3.5 (95% CI 3.0 to 4.1) for connective tissue diseases and 2.3 (95% CI 2.0 to 2.7) for chronic pulmonary diseases. aORs were also increased at 2.8 (95% CI 1.9 to 4.1) and 4.5 (95% CI 2.5 to 8.2) for mild and moderate-to-severe liver disease, respectively, and 4.2 (95% CI 3.4 to 5.2) for renal disease. CONCLUSION: This large population-based study provides evidence for an increasing ON incidence in the general population and documents an association between several common comorbid conditions and risk of ON.",2018 Feb 8,"['Dima, Alina', 'Pedersen, Alma Becic', 'Pedersen, Lars', 'Baicus, Cristian', 'Thomsen, Reimar Wernich']",BMJ Open,,,True
c8d6b93a43ec16e86c706d638d1de31ffd961588,PMC,Association of common comorbidities with osteonecrosis: a nationwide population-based case–control study in Denmark,http://dx.doi.org/10.1136/bmjopen-2017-020680,PMC5829903,29439082,CC BY-NC,"OBJECTIVE: To examine recent time trends in the incidence of osteonecrosis (ON) in Denmark and to investigate different common comorbidities association with ON in a population-based setting. METHODS: Using Danish medical databases, we included all patients with a first-time hospital diagnosis of ON during 1995–2012. Each ON case was matched with 10 randomly selected population control subjects from general population. For all participants, we obtained a complete hospital history of comorbidities included in the CharlsonComorbidity Index 5 years preceding the inclusion date. RESULTS: 4107 ON cases and 41 063 controls were included. The incidence of ON increased from 3.9 in 1995 to 5.5 in 2012 per 100 000 inhabitants. Solid cancer was the most common comorbidity, associated with an adjusted OR (aOR) for ON of 2.0 (95% CI 1.7 to 2.2). For advanced metastatic cancer, leukaemia and lymphoma, aORs of ON were 3.4 (95% CI 2.5 to 4.5), 4.3 (95% CI 2.7 to 7.0) and 5.8 (95% CI 4.3 to 7.8), respectively. Among other chronic conditions, aORs were 3.5 (95% CI 3.0 to 4.1) for connective tissue diseases and 2.3 (95% CI 2.0 to 2.7) for chronic pulmonary diseases. aORs were also increased at 2.8 (95% CI 1.9 to 4.1) and 4.5 (95% CI 2.5 to 8.2) for mild and moderate-to-severe liver disease, respectively, and 4.2 (95% CI 3.4 to 5.2) for renal disease. CONCLUSION: This large population-based study provides evidence for an increasing ON incidence in the general population and documents an association between several common comorbid conditions and risk of ON.",2018 Feb 8,"['Dima, Alina', 'Pedersen, Alma Becic', 'Pedersen, Lars', 'Baicus, Cristian', 'Thomsen, Reimar Wernich']",BMJ Open,,,True
5825a757579db81832b4cde39af407036f81c81e,PMC,Association of common comorbidities with osteonecrosis: a nationwide population-based case–control study in Denmark,http://dx.doi.org/10.1136/bmjopen-2017-020680,PMC5829903,29439082,CC BY-NC,"OBJECTIVE: To examine recent time trends in the incidence of osteonecrosis (ON) in Denmark and to investigate different common comorbidities association with ON in a population-based setting. METHODS: Using Danish medical databases, we included all patients with a first-time hospital diagnosis of ON during 1995–2012. Each ON case was matched with 10 randomly selected population control subjects from general population. For all participants, we obtained a complete hospital history of comorbidities included in the CharlsonComorbidity Index 5 years preceding the inclusion date. RESULTS: 4107 ON cases and 41 063 controls were included. The incidence of ON increased from 3.9 in 1995 to 5.5 in 2012 per 100 000 inhabitants. Solid cancer was the most common comorbidity, associated with an adjusted OR (aOR) for ON of 2.0 (95% CI 1.7 to 2.2). For advanced metastatic cancer, leukaemia and lymphoma, aORs of ON were 3.4 (95% CI 2.5 to 4.5), 4.3 (95% CI 2.7 to 7.0) and 5.8 (95% CI 4.3 to 7.8), respectively. Among other chronic conditions, aORs were 3.5 (95% CI 3.0 to 4.1) for connective tissue diseases and 2.3 (95% CI 2.0 to 2.7) for chronic pulmonary diseases. aORs were also increased at 2.8 (95% CI 1.9 to 4.1) and 4.5 (95% CI 2.5 to 8.2) for mild and moderate-to-severe liver disease, respectively, and 4.2 (95% CI 3.4 to 5.2) for renal disease. CONCLUSION: This large population-based study provides evidence for an increasing ON incidence in the general population and documents an association between several common comorbid conditions and risk of ON.",2018 Feb 8,"['Dima, Alina', 'Pedersen, Alma Becic', 'Pedersen, Lars', 'Baicus, Cristian', 'Thomsen, Reimar Wernich']",BMJ Open,,,False
020f7bf3262c66d41f9cd3c87a8b8319377b6bb3,PMC,Association of common comorbidities with osteonecrosis: a nationwide population-based case–control study in Denmark,http://dx.doi.org/10.1136/bmjopen-2017-020680,PMC5829903,29439082,CC BY-NC,"OBJECTIVE: To examine recent time trends in the incidence of osteonecrosis (ON) in Denmark and to investigate different common comorbidities association with ON in a population-based setting. METHODS: Using Danish medical databases, we included all patients with a first-time hospital diagnosis of ON during 1995–2012. Each ON case was matched with 10 randomly selected population control subjects from general population. For all participants, we obtained a complete hospital history of comorbidities included in the CharlsonComorbidity Index 5 years preceding the inclusion date. RESULTS: 4107 ON cases and 41 063 controls were included. The incidence of ON increased from 3.9 in 1995 to 5.5 in 2012 per 100 000 inhabitants. Solid cancer was the most common comorbidity, associated with an adjusted OR (aOR) for ON of 2.0 (95% CI 1.7 to 2.2). For advanced metastatic cancer, leukaemia and lymphoma, aORs of ON were 3.4 (95% CI 2.5 to 4.5), 4.3 (95% CI 2.7 to 7.0) and 5.8 (95% CI 4.3 to 7.8), respectively. Among other chronic conditions, aORs were 3.5 (95% CI 3.0 to 4.1) for connective tissue diseases and 2.3 (95% CI 2.0 to 2.7) for chronic pulmonary diseases. aORs were also increased at 2.8 (95% CI 1.9 to 4.1) and 4.5 (95% CI 2.5 to 8.2) for mild and moderate-to-severe liver disease, respectively, and 4.2 (95% CI 3.4 to 5.2) for renal disease. CONCLUSION: This large population-based study provides evidence for an increasing ON incidence in the general population and documents an association between several common comorbid conditions and risk of ON.",2018 Feb 8,"['Dima, Alina', 'Pedersen, Alma Becic', 'Pedersen, Lars', 'Baicus, Cristian', 'Thomsen, Reimar Wernich']",BMJ Open,,,False
b3ed8e8e1f4e6bb576910bc4506303b525c2a1e5,PMC,Enhancing ‘Whole-of-Government’ Response to Biological Events in Korea: Able Response 2014,http://dx.doi.org/10.24171/j.phrp.2018.9.1.06,PMC5831680,29503803,CC BY-NC-ND,"Since 2011, the Republic of Korea (ROK) and United States (U.S.) have been collaborating to conduct inter- and intra-governmental exercises to jointly respond to biological events in Korea. These exercises highlight U.S. interest in increasing its global biosurveillance capability and the ROK’s interest in improving cooperation among ministries to respond to crises. With Able Response (AR) exercises, the ROK and U.S. have improved coordination among US and ROK government and defense agencies responding to potential bio-threats and identified additional areas on which to apply refinements in policies and practices. In 2014, the AR exercise employed a Biosurveillance Portal (BSP) to facilitate more effective communication among participating agencies and countries including Australia. In the present paper, we seek to provide a comprehensive assessment of the AR 2014 (AR14) exercise and make recommendations for future improvements. Incorporating a more realistic response in future scenarios by integrating a tactical response episode in the exercise is recommended.",2018 Feb,"['Tak, Sangwoo', 'Jareb, Anton', 'Choi, Suon', 'Sikes, Marvin', 'Choi, Yeon Hwa', 'Boo, Hyeong-wook']",Osong Public Health Res Perspect,,,True
d92d741f65164c7fe568413caebac49e13c4916e,PMC,A Joint Exercise against Intentional Biothreats,http://dx.doi.org/10.24171/j.phrp.2018.9.1.01,PMC5831684,29503798,CC BY-NC-ND,,2018 Feb,"['Cho, Hae-Wol', 'Chu, Chaeshin']",Osong Public Health Res Perspect,,,True
ce0ea5e3b418366d8dab2a4c5a98266c8880a156,PMC,Update of the ERS international Adult Respiratory Medicine syllabus for postgraduate training,http://dx.doi.org/10.1183/20734735.019317,PMC5832014,29515664,CC BY-NC,"First published in 2006, the first European core syllabus in Adult Respiratory Medicine was developed with the intention of harmonising education and training throughout Europe. Internationally recognised by the European Union of Medical Specialists and identified as the first document of its kind in respiratory medicine, it has provided a comprehensive guide for both local and national institutions in the development of adult respiratory training programmes. Like all fields in education, respiratory medicine is an ever-changing area and as such, respective syllabi, curricula and training programmes must adapt and diversify in line with the evolution of core medical concepts. Given the proven importance of the Adult Respiratory Medicine syllabus from both a national and international standpoint, it is of equal importance that said syllabus remains abreast of emerging trends so as to sustain the synchronisation of respiratory medicine in Europe. In order to develop an updated programme, a comprehensive review process of the current syllabus is a necessary endeavour and a step that the European Respiratory Society (ERS) has undertaken through the process of a needs assessment.",2018 Mar,"['Tabin, Nathalie', 'Mitchell, Sharon', 'O’Connell, Elaine', 'Stolz, Daiana', 'Rohde, Gernot']",Breathe (Sheff),,,True
1c53a2402a62d690283249f511d98ba1fa975499,PMC,Update of the ERS international Adult Respiratory Medicine syllabus for postgraduate training,http://dx.doi.org/10.1183/20734735.019317,PMC5832014,29515664,CC BY-NC,"First published in 2006, the first European core syllabus in Adult Respiratory Medicine was developed with the intention of harmonising education and training throughout Europe. Internationally recognised by the European Union of Medical Specialists and identified as the first document of its kind in respiratory medicine, it has provided a comprehensive guide for both local and national institutions in the development of adult respiratory training programmes. Like all fields in education, respiratory medicine is an ever-changing area and as such, respective syllabi, curricula and training programmes must adapt and diversify in line with the evolution of core medical concepts. Given the proven importance of the Adult Respiratory Medicine syllabus from both a national and international standpoint, it is of equal importance that said syllabus remains abreast of emerging trends so as to sustain the synchronisation of respiratory medicine in Europe. In order to develop an updated programme, a comprehensive review process of the current syllabus is a necessary endeavour and a step that the European Respiratory Society (ERS) has undertaken through the process of a needs assessment.",2018 Mar,"['Tabin, Nathalie', 'Mitchell, Sharon', 'O’Connell, Elaine', 'Stolz, Daiana', 'Rohde, Gernot']",Breathe (Sheff),,,False
d9e24a56fd02e643de973aab5753dbf7accc1e90,PMC,"Comparison of three multiplex PCR assays for detection of respiratory viruses: Anyplex II RV16, AdvanSure RV, and Real‐Q RV",http://dx.doi.org/10.1002/jcla.22230,PMC5836940,28397965,CC BY-NC,"BACKGROUND: Due to its great sensitivity, the nucleic acid amplification test (NAAT) is widely used for detection of respiratory viruses (RV). However, few reports have described a direct comparison between multiplex RT‐PCR assays for RV. The objective of this study was to perform a direct comparison of three multiplex RT‐PCR assays for the detection of respiratory viruses. METHODS: A total of 201 respiratory samples (161 nasopharyngeal swab samples and 40 sputum samples) were tested with three commercial RV assays: Seegene Anyplex II RV16 (AP), LG AdvanSure RV (AD), and Biosewoom Real‐Q RV (RQ). The additional tests for the discrepant results were conducted by repeat RV assay or monoplex PCR coupled direct sequencing. Data analysis using percent agreement, kappa, and prevalence‐adjusted and bias‐adjusted kappa (PABAK) values was performed for comparisons among the three RV assays. RESULTS: Of the 201 samples, AP, AD, and RQ detected 105 (52.2%), 99 (49.3%), and 95 (47.3%) positive cases respectively. The overall agreement, kappa, and PABAK values for the three assays ranged between 97%‐98%, 0.76‐0.86, and 0.93‐0.96 respectively. The performance of the three assays was very similar, with 94%‐100% agreement for all comparisons, each virus types. The additional testing of samples showed discrepant results demonstrating that AD assay had the highest rate of concordance with original results. CONCLUSIONS: We suggest that all multiplex assay would be suitable for the detection of for respiratory viruses in clinical setting.",2017 Apr 11,"['Yun, Seung Gyu', 'Kim, Min Young', 'Choi, Jong Moon', 'Lee, Chang Kyu', 'Lim, Chae Seung', 'Cho, Yunjung', 'Suh, In Bum']",J Clin Lab Anal,,,True
f7748ce96d52eeafe6b08a42b2f9f1774b373f78,PMC,Beyond self-eating: The control of nonautophagic functions and signaling pathways by autophagy-related proteins,http://dx.doi.org/10.1083/jcb.201706157,PMC5839790,29237720,CC BY-NC-SA,"The identification of conserved autophagy-related proteins (ATGs) that mediate bulk degradation of cytosolic material laid the foundation for breakthroughs linking autophagy to a litany of physiological processes and disease conditions. Recent discoveries are revealing that these same ATGs orchestrate processes that are related to, and yet clearly distinct from, classic autophagy. Autophagy-related functions include secretion, trafficking of phagocytosed material, replication and egress of viral particles, and regulation of inflammatory and immune signaling cascades. Here, we define common processes dependent on ATGs, and discuss the challenges in mechanistically separating autophagy from these related pathways. Elucidating the molecular events that distinguish how individual ATGs function promises to improve our understanding of the origin of diseases ranging from autoimmunity to cancer.",2018 Mar 5,"['Cadwell, Ken', 'Debnath, Jayanta']",J Cell Biol,,,True
e6d882be4961d1bdd7507b4a29d86b650de0895d,PMC,Middle East respiratory syndrome: what we learned from the 2015 outbreak in the Republic of Korea,http://dx.doi.org/10.3904/kjim.2018.031,PMC5840604,29506344,CC BY-NC,"Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in 2012. The 2015 Korea outbreak of MERSCoV involved 186 cases, including 38 fatalities. A total of 83% of transmission events were due to five superspreaders, and 44% of the 186 MERS cases were the patients who had been exposed in nosocomial transmission at 16 hospitals. The epidemic lasted for 2 months and the government quarantined 16,993 individuals for 14 days to control the outbreak. This outbreak provides a unique opportunity to fill the gap in our knowledge of MERS-CoV infection. Therefore, in this paper, we review the literature on epidemiology, virology, clinical features, and prevention of MERS-CoV, which were acquired from the 2015 Korea outbreak of MERSCoV.",2018 Mar 27,"['Oh, Myoung-don', 'Park, Wan Beom', 'Park, Sang-Won', 'Choe, Pyoeng Gyun', 'Bang, Ji Hwan', 'Song, Kyoung-Ho', 'Kim, Eu Suk', 'Kim, Hong Bin', 'Kim, Nam Joong']",Korean J Intern Med,,,True
27d9e8f9f893c005e551b219680b7832eac40fca,PMC,Infectious complications after hematopoietic stem cell transplantation: current status and future perspectives in Korea,http://dx.doi.org/10.3904/kjim.2018.036,PMC5840605,29506345,CC BY-NC,"Hematopoietic stem cell transplantation (HSCT) is a treatment for hematologic malignancies, immune deficiencies, or genetic diseases, ect. Recently, the number of HSCTs performed in Korea has increased and the outcomes have improved. However, infectious complications account for most of the morbidity and mortality after HSCT. Post-HSCT infectious complications are usually classified according to the time after HSCT: pre-engraftment, immediate post-engraftment, and late post-engraftment period. In addition, the types and risk factors of infectious complications differ according to the stem cell source, donor type, conditioning intensity, region, prophylaxis strategy, and comorbidities, such as graft-versushost disease and invasive fungal infection. In this review, we summarize infectious complications after HSCT, focusing on the Korean perspectives.",2018 Mar 27,"['Cho, Sung-Yeon', 'Lee, Hyeon-Jeong', 'Lee, Dong-Gun']",Korean J Intern Med,,,True
9e91991355bc76a376b379387983a5ac08f179ab,PMC,Low-fidelity Venezuelan equine encephalitis virus polymerase mutants to improve live-attenuated vaccine safety and efficacy,http://dx.doi.org/10.1093/ve/vey004,PMC5841381,29593882,CC BY-NC,"During RNA virus replication, there is the potential to incorporate mutations that affect virulence or pathogenesis. For live-attenuated vaccines, this has implications for stability, as replication may result in mutations that either restore the wild-type phenotype via reversion or compensate for the attenuating mutations by increasing virulence (pseudoreversion). Recent studies have demonstrated that altering the mutation rate of an RNA virus is an effective attenuation tool. To validate the safety of low-fidelity mutations to increase vaccine attenuation, several mutations in the RNA-dependent RNA-polymerase (RdRp) were tested in the live-attenuated Venezuelan equine encephalitis virus vaccine strain, TC-83. Next generation sequencing after passage in the presence of mutagens revealed a mutant containing three mutations in the RdRp, TC-83 3x, to have decreased replication fidelity, while a second mutant, TC-83 4x displayed no change in fidelity, but shared many phenotypic characteristics with TC-83 3x. Both mutants exhibited increased, albeit inconsistent attenuation in an infant mouse model, as well as increased immunogenicity and complete protection against lethal challenge of an adult murine model compared with the parent TC-83. During serial passaging in a highly permissive model, the mutants increased in virulence but remained less virulent than the parent TC-83. These results suggest that the incorporation of low-fidelity mutations into the RdRp of live-attenuated vaccines for RNA viruses can confer increased immunogenicity whilst showing some evidence of increased attenuation. However, while in theory such constructs may result in more effective vaccines, the instability of the vaccine phenotype decreases the likelihood of this being an effective vaccine strategy.",2018 Mar 6,"['Kautz, Tiffany F', 'Guerbois, Mathilde', 'Khanipov, Kamil', 'Patterson, Edward I', 'Langsjoen, Rose M', 'Yun, Ruimei', 'Warmbrod, Kelsey L', 'Fofanov, Yuriy', 'Weaver, Scott C', 'Forrester, Naomi L']",Virus Evol,,,True
0a2ded6cbd632857d491140a57f2773c3610b10b,PMC,MRI findings of neuronal ceroid lipofuscinosis in a cat,http://dx.doi.org/10.1177/2055116918757330,PMC5843104,29531776,CC BY-NC,"CASE SUMMARY: A 2-year-old male domestic shorthair cat presented to the University of Liverpool Small Animal Teaching Hospital with a 2 week history of altered mentation, blindness and focal epileptic seizures. MRI examination revealed generalised cerebral and cerebellar atrophy, diffuse T2-weighted hyperintensity of the white matter and meningeal thickening. Neuronal ceroid lipofuscinosis was confirmed on post-mortem examination. RELEVANCE AND NOVEL INFORMATION: This is the first report of the MRI findings of neuronal ceroid lipofuscinosis in a cat.",2018 Mar 5,"['White, Crystal', 'Mortier, Jeremy', 'Verin, Ranieri', 'Maddox, Thomas', 'Goncalves, Rita', 'Sanchez-Masian, Daniel']",JFMS Open Rep,,,True
d639dcd741bb9859008178d4f6b2c49e6398b861,PMC,Health-seeking behavior and transmission dynamics in the control of influenza infection among different age groups,http://dx.doi.org/10.2147/IDR.S153797,PMC5846056,29563814,CC BY-NC,"BACKGROUND: It has been found that health-seeking behavior has a certain impact on influenza infection. However, behaviors with/without risk perception on the control of influenza transmission among age groups have not been well quantified. OBJECTIVES: The purpose of this study was to assess to what extent, under scenarios of with/without control and preventive/protective behaviors, the age-specific network-driven risk perception influences influenza infection. MATERIALS AND METHODS: A behavior-influenza model was used to estimate the spread rate of age-specific risk perception in response to an influenza outbreak. A network-based information model was used to assess the effect of network-driven risk perception information transmission on influenza infection. A probabilistic risk model was used to assess the infection risk effect of risk perception with a health behavior change. RESULTS: The age-specific overlapping percentage was estimated to be 40%–43%, 55%–60%, and 19%–35% for child, teenage and adult, and elderly age groups, respectively. Individuals perceive the preventive behavior to improve risk perception information transmission among teenage and adult and elderly age groups, but not in the child age group. The population with perceived health behaviors could not effectively decrease the percentage of infection risk in the child age group, whereas for the elderly age group, the percentage of decrease in infection risk was more significant, with a 97.5th percentile estimate of 97%. CONCLUSION: The present integrated behavior-infection model can help health authorities in communicating health messages for an intertwined belief network in which health-seeking behavior plays a key role in controlling influenza infection.",2018 Mar 6,"['You, Shu-Han', 'Chen, Szu-Chieh', 'Liao, Chung-Min']",Infect Drug Resist,,,True
bf67288452ef517671172909e5613a73b73a36a6,PMC,Building the atomic model of a boreal lake virus of unknown fold in a 3.9 Å cryo-EM map,http://dx.doi.org/10.1016/j.jsb.2017.10.010,PMC5847487,29092773,CC BY-NC-ND,"We report here the protocol adopted to build the atomic model of the newly discovered virus FLiP (Flavobacterium infecting, lipid-containing phage) into 3.9 Å cryo-electron microscopy (cryo-EM) maps. In particular, this report discusses the combination of density modification procedures, automatic model building and bioinformatics tools applied to guide the tracing of the major capsid protein (MCP) of this virus. The protocol outlined here may serve as a reference for future structural determination by cryo-EM of viruses lacking detectable structural homologues.",2018 Apr,"['De Colibus, Luigi', 'Stuart, David I.']",J Struct Biol,,,False
517698251b94fac6d80edcc4644e2448a4efd4ef,PMC,Improved Algorithmic Complexity for the 3SEQ Recombination Detection Algorithm,http://dx.doi.org/10.1093/molbev/msx263,PMC5850291,29029186,CC BY-NC,"Identifying recombinant sequences in an era of large genomic databases is challenging as it requires an efficient algorithm to identify candidate recombinants and parents, as well as appropriate statistical methods to correct for the large number of comparisons performed. In 2007, a computation was introduced for an exact nonparametric mosaicism statistic that gave high-precision P values for putative recombinants. This exact computation meant that multiple-comparisons corrected P values also had high precision, which is crucial when performing millions or billions of tests in large databases. Here, we introduce an improvement to the algorithmic complexity of this computation from O(mn(3)) to O(mn(2)), where m and n are the numbers of recombination-informative sites in the candidate recombinant. This new computation allows for recombination analysis to be performed in alignments with thousands of polymorphic sites. Benchmark runs are presented on viral genome sequence alignments, new features are introduced, and applications outside recombination analysis are discussed.",2018 Jan 3,"['Lam, Ha Minh', 'Ratmann, Oliver', 'Boni, Maciej F']",Mol Biol Evol,,,True
e012c42cc9de8f02ca1e254e76a85a67286070ea,PMC,Risk factors for severe bronchiolitis caused by respiratory virus infections among Mexican children in an emergency department,http://dx.doi.org/10.1097/MD.0000000000010057,PMC5851717,29489664,CC BY-ND,"Severe bronchiolitis is the most common reason for hospitalization among children younger than 2 years. This study analyzed the prevalence of community-acquired respiratory virus infection and the risk factors for hospitalization of Mexican children with severe bronchiolitis treated in an Emergency department. This retrospective study included 134 children 2 years or younger with severe viral bronchiolitis, and 134 healthy age-matched controls. The study period was September 2012 to January 2015. We determined the viral etiology and coinfections with multiple viruses and compared the risk factors detected in children with severe viral bronchiolitis with those in the control group. A total of 153 respiratory viruses in these 134 patients, single or mixed infections, were identified: respiratory syncytial virus (RSV) type A or B was the most frequently detected (23.6% and 17.6%, respectively), followed by rhinovirus (RV; 16.3%) and parainfluenza virus (PIV) type 3 (12.4%). Coinfections of 2 respiratory viruses were found in 14.2% of cases; all cases had either RSV type A or B with another virus, the most common being parainfluenza virus or rhinovirus. Exposure to cigarette smoking was independently associated with hospitalization for severe bronchiolitis (OR, 3.5; 95% CI, 1.99–6.18; P = .0001), and having completed the vaccination schedule for their age was a protective factor against adverse outcome (OR, 0.55; 95% CI, 0.35–0.87; P = .010). RSV is a common infection among young children with severe bronchiolitis; thus, developing a vaccine against RSV is essential. Campaigns to reinforce the importance of avoiding childhood exposure to cigarette smoke are also needed.",2018 Mar 2,"['Robledo-Aceves, Mireya', 'Moreno-Peregrina, María de Jesús', 'Velarde-Rivera, Fernando', 'Ascencio-Esparza, Elba', 'Preciado-Figueroa, Francisco M.', 'Caniza, Miguela A.', 'Escobedo-Melendez, Griselda']",Medicine (Baltimore),,,True
0e63d19fa3d2ebfcc7cdb06f85225ae0489acf8e,PMC,Chinese research into severe ulcerative colitis has increased in quantity and complexity,http://dx.doi.org/10.12998/wjcc.v6.i3.35,PMC5852397,29564356,CC BY-NC,"AIM: To investigate the current state of research output from Chinese studies into severe ulcerative colitis (SUC) using a bibliometric analysis of publications. METHODS: The contents of the Chinese periodical databases WANFANG, VIP, and China National Knowledge Infrastructure were searched for all papers regarding UC or SUC published in last the 15 years (from 2001 to 2015). The number of publications in each year was recorded to assess the temporal trends of research output. All SUC related publications were downloaded and the complexity of this research was evaluated with methods described previously. The number of patients with SUC reported each year was recorded and their clinical characteristics were analyzed using information available in the relevant papers. RESULTS: There were 13499 publications regarding UC published in Chinese medical journals between 2001 and 2015, of which 201 focused on SUC. The number of publications increased rapidly with more than half of all papers being published in the most recent 5-year period. There was a significant increase in analytical studies and clinical trials over the study period (P < 0.01), with research into the management of SUC, included pharmacotherapy, nutrition support as well as surgery, predominating. Almost half (46.2%) of the observational analytical studies and clinical trials focused on Traditional Chinese Medicine, with little research on the efficacy of cyclosporin and infliximab in disease management. About 6222 patients with SUC were reported in the 201 SUC relevant papers, with a ratio of male/female of 1.38. The number of patients reported in each 5-year period significantly increased. The colectomy rate and short-term mortality rate were 7.7% and 0.8% respectively. The most commonly employed operation was total proctocolectomy with ileal pouch-anal anastomosis. CONCLUSION: The output and complexity of research related to SUC in China increased significantly over the previous 15 years, however few of these studies focused on salvage therapy.",2018 Mar 16,"['Luo, Cheng-Xin', 'Wen, Zhong-Hui', 'Zhen, Yu', 'Wang, Zhu-Jun', 'Mu, Jing-Xi', 'Zhu, Min', 'Ouyang, Qin', 'Zhang, Hu']",World J Clin Cases,,,True
11ebffa99e4b093c6304549246b534983012f909,PMC,Discrimination of Kawasaki disease with concomitant adenoviral detection differentiating from isolated adenoviral infection,http://dx.doi.org/10.3345/kjp.2018.61.2.43,PMC5854841,29563943,CC BY-NC,"PURPOSE: Human adenovirus infection mimics Kawasaki disease (KD) but can be detected in KD patients. The aim of this study was to determine the clinical differences between KD with adenovirus infection and only adenoviral infection and to identify biomarkers for prediction of adenovirus-positive KD from isolated adenoviral infection. METHODS: A total of 147 patients with isolated adenovirus were identified by quantitative polymerase chain reaction. In addition, 11 patients having KD with adenovirus, who were treated with intravenous immunoglobulin therapy during the acute phase of KD were also evaluated. RESULTS: Compared with the adenoviral infection group, the KD with adenovirus group was significantly associated with frequent lip and tongue changes, skin rash and changes in the extremities. In the laboratory parameters, higher C-reactive protein (CRP) level and presence of hypoalbuminemia and sterile pyuria were significantly associated with the KD group. In the multivariate analysis, lip and tongue changes (odds ratio [OR], 1.416; 95% confidence interval [CI], 1.151–1.741; P=0.001), high CRP level (OR, 1.039; 95% CI 1.743–1.454; P= 0.021) and sterile pyuria (OR 1.052; 95% CI 0.861–1.286; P=0.041) were the significant predictive factors of KD. In addition, the cutoff CRP level related to KD with adenoviral detection was 56 mg/L, with a sensitivity of 81.8% and a specificity of 75.9%. CONCLUSION: Lip and tongue changes, higher serum CRP level and sterile pyuria were significantly correlated with adenovirus-positive KD.",2018 Feb 28,"['Kim, Jong Han', 'Kang, Hye Ree', 'Kim, Su Yeong', 'Ban, Ji-Eun']",Korean J Pediatr,,,True
801d5411eaa50cb50b03e37bf199b1636341c5c2,PMC,Daylight-driven rechargeable antibacterial and antiviral nanofibrous membranes for bioprotective applications,http://dx.doi.org/10.1126/sciadv.aar5931,PMC5856488,29556532,CC BY-NC,"Emerging infectious diseases (EIDs) are a significant burden on global economies and public health. Most present personal protective equipment used to prevent EID transmission and infections is typically devoid of antimicrobial activity. We report on green bioprotective nanofibrous membranes (RNMs) with rechargeable antibacterial and antiviral activities that can effectively produce biocidal reactive oxygen species (ROS) solely driven by the daylight. The premise of the design is that the photoactive RNMs can store the biocidal activity under light irradiation and readily release ROS under dim light or dark conditions, making the biocidal function “always online.” The resulting RNMs exhibit integrated properties of fast ROS production, ease of activity storing, long-term durability, robust breathability, interception of fine particles (>99%), and high bactericidal (>99.9999%) and virucidal (>99.999%) efficacy, which enabled to serve as a scalable biocidal layer for protective equipment by providing contact killing against pathogens either in aerosol or in liquid forms. The successful synthesis of these fascinating materials may provide new insights into the development of protection materials in a sustainable, self-recharging, and structurally adaptive form.",2018 Mar 16,"['Si, Yang', 'Zhang, Zheng', 'Wu, Wanrong', 'Fu, Qiuxia', 'Huang, Kang', 'Nitin, Nitin', 'Ding, Bin', 'Sun, Gang']",Sci Adv,,,True
3b2a3144d30ad17af23777adadd8386503498bcf,PMC,Daylight-driven rechargeable antibacterial and antiviral nanofibrous membranes for bioprotective applications,http://dx.doi.org/10.1126/sciadv.aar5931,PMC5856488,29556532,CC BY-NC,"Emerging infectious diseases (EIDs) are a significant burden on global economies and public health. Most present personal protective equipment used to prevent EID transmission and infections is typically devoid of antimicrobial activity. We report on green bioprotective nanofibrous membranes (RNMs) with rechargeable antibacterial and antiviral activities that can effectively produce biocidal reactive oxygen species (ROS) solely driven by the daylight. The premise of the design is that the photoactive RNMs can store the biocidal activity under light irradiation and readily release ROS under dim light or dark conditions, making the biocidal function “always online.” The resulting RNMs exhibit integrated properties of fast ROS production, ease of activity storing, long-term durability, robust breathability, interception of fine particles (>99%), and high bactericidal (>99.9999%) and virucidal (>99.999%) efficacy, which enabled to serve as a scalable biocidal layer for protective equipment by providing contact killing against pathogens either in aerosol or in liquid forms. The successful synthesis of these fascinating materials may provide new insights into the development of protection materials in a sustainable, self-recharging, and structurally adaptive form.",2018 Mar 16,"['Si, Yang', 'Zhang, Zheng', 'Wu, Wanrong', 'Fu, Qiuxia', 'Huang, Kang', 'Nitin, Nitin', 'Ding, Bin', 'Sun, Gang']",Sci Adv,,,False
23fcb75440f439f30f656e0c6b47c6f565f32ef2,PMC,Role of viral and bacterial pathogens in causing pneumonia among Western Australian children: a case–control study protocol,http://dx.doi.org/10.1136/bmjopen-2017-020646,PMC5857668,29549211,CC BY-NC,"INTRODUCTION: Pneumonia is the leading cause of childhood morbidity and mortality globally. Introduction of the conjugate Haemophilus influenzae B and multivalent pneumococcal vaccines in developed countries including Australia has significantly reduced the overall burden of bacterial pneumonia. With the availability of molecular diagnostics, viruses are frequently detected in children with pneumonia either as primary pathogens or predispose to secondary bacterial infection. Many respiratory pathogens that are known to cause pneumonia are also identified in asymptomatic children, so the true contribution of these pathogens to childhood community-acquired pneumonia (CAP) remains unclear. Since the introduction of pneumococcal vaccines, very few comprehensive studies from developed countries have attempted to determine the bacterial and viral aetiology of pneumonia. We aim to determine the contribution of bacteria and viruses to childhood CAP to inform further development of effective diagnosis, treatment and preventive strategies. METHODS AND ANALYSIS: We are conducting a prospective case–control study (PneumoWA) where cases are children with radiologically confirmed pneumonia admitted to Princess Margaret Hospital for Children (PMH) and controls are healthy children identified from PMH outpatient clinics and from local community immunisation clinics. The case–control ratio is 1:1 with 250 children to be recruited in each arm. Nasopharyngeal swabs are collected from both cases and controls to detect the presence of viruses and bacteria by PCR; pathogen load will be assessed by quantitative PCR. The prevalence of pathogens detected in cases and controls will be compared, the OR of detection and population attributable fraction to CAP for each pathogen will be determined; relationships between pathogen load and disease status and severity will be explored. ETHICS AND DISSEMINATION: This study has been approved by the human research ethics committees of PMH, Perth, Australia (PMH HREC REF 2014117EP). Findings will be disseminated at research conferences and in peer-reviewed journals.",2018 Mar 16,"['Bhuiyan, Mejbah Uddin', 'Snelling, Thomas L', 'West, Rachel', 'Lang, Jurissa', 'Rahman, Tasmina', 'Borland, Meredith L', 'Thornton, Ruth', 'Kirkham, Lea-Ann', 'Sikazwe, Chisha', 'Martin, Andrew C', 'Richmond, Peter C', 'Smith, David W', 'Jaffe, Adam', 'Blyth, Christopher C']",BMJ Open,,,True
34d485e6c776b7e4e28bab88bdd133aa4d43e4b2,PMC,Role of viral and bacterial pathogens in causing pneumonia among Western Australian children: a case–control study protocol,http://dx.doi.org/10.1136/bmjopen-2017-020646,PMC5857668,29549211,CC BY-NC,"INTRODUCTION: Pneumonia is the leading cause of childhood morbidity and mortality globally. Introduction of the conjugate Haemophilus influenzae B and multivalent pneumococcal vaccines in developed countries including Australia has significantly reduced the overall burden of bacterial pneumonia. With the availability of molecular diagnostics, viruses are frequently detected in children with pneumonia either as primary pathogens or predispose to secondary bacterial infection. Many respiratory pathogens that are known to cause pneumonia are also identified in asymptomatic children, so the true contribution of these pathogens to childhood community-acquired pneumonia (CAP) remains unclear. Since the introduction of pneumococcal vaccines, very few comprehensive studies from developed countries have attempted to determine the bacterial and viral aetiology of pneumonia. We aim to determine the contribution of bacteria and viruses to childhood CAP to inform further development of effective diagnosis, treatment and preventive strategies. METHODS AND ANALYSIS: We are conducting a prospective case–control study (PneumoWA) where cases are children with radiologically confirmed pneumonia admitted to Princess Margaret Hospital for Children (PMH) and controls are healthy children identified from PMH outpatient clinics and from local community immunisation clinics. The case–control ratio is 1:1 with 250 children to be recruited in each arm. Nasopharyngeal swabs are collected from both cases and controls to detect the presence of viruses and bacteria by PCR; pathogen load will be assessed by quantitative PCR. The prevalence of pathogens detected in cases and controls will be compared, the OR of detection and population attributable fraction to CAP for each pathogen will be determined; relationships between pathogen load and disease status and severity will be explored. ETHICS AND DISSEMINATION: This study has been approved by the human research ethics committees of PMH, Perth, Australia (PMH HREC REF 2014117EP). Findings will be disseminated at research conferences and in peer-reviewed journals.",2018 Mar 16,"['Bhuiyan, Mejbah Uddin', 'Snelling, Thomas L', 'West, Rachel', 'Lang, Jurissa', 'Rahman, Tasmina', 'Borland, Meredith L', 'Thornton, Ruth', 'Kirkham, Lea-Ann', 'Sikazwe, Chisha', 'Martin, Andrew C', 'Richmond, Peter C', 'Smith, David W', 'Jaffe, Adam', 'Blyth, Christopher C']",BMJ Open,,,True
38197f25eb256e1433b1fcb3ead9cbd5dfa0eaea,PMC,Role of viral and bacterial pathogens in causing pneumonia among Western Australian children: a case–control study protocol,http://dx.doi.org/10.1136/bmjopen-2017-020646,PMC5857668,29549211,CC BY-NC,"INTRODUCTION: Pneumonia is the leading cause of childhood morbidity and mortality globally. Introduction of the conjugate Haemophilus influenzae B and multivalent pneumococcal vaccines in developed countries including Australia has significantly reduced the overall burden of bacterial pneumonia. With the availability of molecular diagnostics, viruses are frequently detected in children with pneumonia either as primary pathogens or predispose to secondary bacterial infection. Many respiratory pathogens that are known to cause pneumonia are also identified in asymptomatic children, so the true contribution of these pathogens to childhood community-acquired pneumonia (CAP) remains unclear. Since the introduction of pneumococcal vaccines, very few comprehensive studies from developed countries have attempted to determine the bacterial and viral aetiology of pneumonia. We aim to determine the contribution of bacteria and viruses to childhood CAP to inform further development of effective diagnosis, treatment and preventive strategies. METHODS AND ANALYSIS: We are conducting a prospective case–control study (PneumoWA) where cases are children with radiologically confirmed pneumonia admitted to Princess Margaret Hospital for Children (PMH) and controls are healthy children identified from PMH outpatient clinics and from local community immunisation clinics. The case–control ratio is 1:1 with 250 children to be recruited in each arm. Nasopharyngeal swabs are collected from both cases and controls to detect the presence of viruses and bacteria by PCR; pathogen load will be assessed by quantitative PCR. The prevalence of pathogens detected in cases and controls will be compared, the OR of detection and population attributable fraction to CAP for each pathogen will be determined; relationships between pathogen load and disease status and severity will be explored. ETHICS AND DISSEMINATION: This study has been approved by the human research ethics committees of PMH, Perth, Australia (PMH HREC REF 2014117EP). Findings will be disseminated at research conferences and in peer-reviewed journals.",2018 Mar 16,"['Bhuiyan, Mejbah Uddin', 'Snelling, Thomas L', 'West, Rachel', 'Lang, Jurissa', 'Rahman, Tasmina', 'Borland, Meredith L', 'Thornton, Ruth', 'Kirkham, Lea-Ann', 'Sikazwe, Chisha', 'Martin, Andrew C', 'Richmond, Peter C', 'Smith, David W', 'Jaffe, Adam', 'Blyth, Christopher C']",BMJ Open,,,False
c9796b987137402c163bb03519d8cd9de9ae99f9,PMC,Public preferences for interventions to prevent emerging infectious disease threats: a discrete choice experiment,http://dx.doi.org/10.1136/bmjopen-2017-017355,PMC5857709,29453294,CC BY-NC,"OBJECTIVE: When faced with an emergent epidemic with high mortality and morbidity potential, policy makers must decide what public health interventions to deploy at different stages of the outbreak. However, almost nothing is known about how the public view these interventions or how they trade off risks (of disease) with inconvenience (of interventions). In this paper, we aim to understand public perceptions on pandemic interventions, as well as to identify if there are any distinct respondent preference classes. DESIGN: A discrete choice experiment. SETTING: This study was fielded in Singapore between November 2012 and February 2013. PARTICIPANTS: A random sample of 500 Singapore residents aged 21 and over, including 271 women and 229 men, was analysed. OUTCOME MEASURES: Demographic information was collected from each participant. Participants were also shown a series of pairs of alternatives, each combining interventions and morbidity, mortality and cost outcomes and declared a preference for one combination. A random utility model was developed to determine the individual’s preference for interventions and a hierarchical cluster analysis was performed to identify distinct respondent preference classes. RESULTS: On average, participants preferred more intense interventions, and preferred scenarios with fewer deaths and lower tax. The number of infections did not significantly influence respondents’ responses. We identified two broad classes of respondents: those who were mortality averse and those who were expenditure averse. Education was found to be a predictor of group membership. CONCLUSION: Overall, there was considerable support for government interventions to prevent or mitigate outbreaks of emerging infectious diseases, including those that greatly restricted individual liberties, as long as the restrictions showed a reasonable chance of reducing the adverse health effects of the outbreak.",2018 Feb 16,"['Cook, Alex R', 'Zhao, Xiahong', 'Chen, Mark I C', 'Finkelstein, Eric A']",BMJ Open,,,True
6a8fc2a90c03d2ade186c1a30777f5e56dc174a0,PMC,Public preferences for interventions to prevent emerging infectious disease threats: a discrete choice experiment,http://dx.doi.org/10.1136/bmjopen-2017-017355,PMC5857709,29453294,CC BY-NC,"OBJECTIVE: When faced with an emergent epidemic with high mortality and morbidity potential, policy makers must decide what public health interventions to deploy at different stages of the outbreak. However, almost nothing is known about how the public view these interventions or how they trade off risks (of disease) with inconvenience (of interventions). In this paper, we aim to understand public perceptions on pandemic interventions, as well as to identify if there are any distinct respondent preference classes. DESIGN: A discrete choice experiment. SETTING: This study was fielded in Singapore between November 2012 and February 2013. PARTICIPANTS: A random sample of 500 Singapore residents aged 21 and over, including 271 women and 229 men, was analysed. OUTCOME MEASURES: Demographic information was collected from each participant. Participants were also shown a series of pairs of alternatives, each combining interventions and morbidity, mortality and cost outcomes and declared a preference for one combination. A random utility model was developed to determine the individual’s preference for interventions and a hierarchical cluster analysis was performed to identify distinct respondent preference classes. RESULTS: On average, participants preferred more intense interventions, and preferred scenarios with fewer deaths and lower tax. The number of infections did not significantly influence respondents’ responses. We identified two broad classes of respondents: those who were mortality averse and those who were expenditure averse. Education was found to be a predictor of group membership. CONCLUSION: Overall, there was considerable support for government interventions to prevent or mitigate outbreaks of emerging infectious diseases, including those that greatly restricted individual liberties, as long as the restrictions showed a reasonable chance of reducing the adverse health effects of the outbreak.",2018 Feb 16,"['Cook, Alex R', 'Zhao, Xiahong', 'Chen, Mark I C', 'Finkelstein, Eric A']",BMJ Open,,,True
e931468d1e309d48644b19abfb4b419f49718c62,PMC,Public preferences for interventions to prevent emerging infectious disease threats: a discrete choice experiment,http://dx.doi.org/10.1136/bmjopen-2017-017355,PMC5857709,29453294,CC BY-NC,"OBJECTIVE: When faced with an emergent epidemic with high mortality and morbidity potential, policy makers must decide what public health interventions to deploy at different stages of the outbreak. However, almost nothing is known about how the public view these interventions or how they trade off risks (of disease) with inconvenience (of interventions). In this paper, we aim to understand public perceptions on pandemic interventions, as well as to identify if there are any distinct respondent preference classes. DESIGN: A discrete choice experiment. SETTING: This study was fielded in Singapore between November 2012 and February 2013. PARTICIPANTS: A random sample of 500 Singapore residents aged 21 and over, including 271 women and 229 men, was analysed. OUTCOME MEASURES: Demographic information was collected from each participant. Participants were also shown a series of pairs of alternatives, each combining interventions and morbidity, mortality and cost outcomes and declared a preference for one combination. A random utility model was developed to determine the individual’s preference for interventions and a hierarchical cluster analysis was performed to identify distinct respondent preference classes. RESULTS: On average, participants preferred more intense interventions, and preferred scenarios with fewer deaths and lower tax. The number of infections did not significantly influence respondents’ responses. We identified two broad classes of respondents: those who were mortality averse and those who were expenditure averse. Education was found to be a predictor of group membership. CONCLUSION: Overall, there was considerable support for government interventions to prevent or mitigate outbreaks of emerging infectious diseases, including those that greatly restricted individual liberties, as long as the restrictions showed a reasonable chance of reducing the adverse health effects of the outbreak.",2018 Feb 16,"['Cook, Alex R', 'Zhao, Xiahong', 'Chen, Mark I C', 'Finkelstein, Eric A']",BMJ Open,,,False
899766dec9eca589cc41bb7fca26b62890155212,PMC,Public preferences for interventions to prevent emerging infectious disease threats: a discrete choice experiment,http://dx.doi.org/10.1136/bmjopen-2017-017355,PMC5857709,29453294,CC BY-NC,"OBJECTIVE: When faced with an emergent epidemic with high mortality and morbidity potential, policy makers must decide what public health interventions to deploy at different stages of the outbreak. However, almost nothing is known about how the public view these interventions or how they trade off risks (of disease) with inconvenience (of interventions). In this paper, we aim to understand public perceptions on pandemic interventions, as well as to identify if there are any distinct respondent preference classes. DESIGN: A discrete choice experiment. SETTING: This study was fielded in Singapore between November 2012 and February 2013. PARTICIPANTS: A random sample of 500 Singapore residents aged 21 and over, including 271 women and 229 men, was analysed. OUTCOME MEASURES: Demographic information was collected from each participant. Participants were also shown a series of pairs of alternatives, each combining interventions and morbidity, mortality and cost outcomes and declared a preference for one combination. A random utility model was developed to determine the individual’s preference for interventions and a hierarchical cluster analysis was performed to identify distinct respondent preference classes. RESULTS: On average, participants preferred more intense interventions, and preferred scenarios with fewer deaths and lower tax. The number of infections did not significantly influence respondents’ responses. We identified two broad classes of respondents: those who were mortality averse and those who were expenditure averse. Education was found to be a predictor of group membership. CONCLUSION: Overall, there was considerable support for government interventions to prevent or mitigate outbreaks of emerging infectious diseases, including those that greatly restricted individual liberties, as long as the restrictions showed a reasonable chance of reducing the adverse health effects of the outbreak.",2018 Feb 16,"['Cook, Alex R', 'Zhao, Xiahong', 'Chen, Mark I C', 'Finkelstein, Eric A']",BMJ Open,,,False
6ea2b79805ea00a8f1bb53db43c3af0dbb066943,PMC,Public preferences for interventions to prevent emerging infectious disease threats: a discrete choice experiment,http://dx.doi.org/10.1136/bmjopen-2017-017355,PMC5857709,29453294,CC BY-NC,"OBJECTIVE: When faced with an emergent epidemic with high mortality and morbidity potential, policy makers must decide what public health interventions to deploy at different stages of the outbreak. However, almost nothing is known about how the public view these interventions or how they trade off risks (of disease) with inconvenience (of interventions). In this paper, we aim to understand public perceptions on pandemic interventions, as well as to identify if there are any distinct respondent preference classes. DESIGN: A discrete choice experiment. SETTING: This study was fielded in Singapore between November 2012 and February 2013. PARTICIPANTS: A random sample of 500 Singapore residents aged 21 and over, including 271 women and 229 men, was analysed. OUTCOME MEASURES: Demographic information was collected from each participant. Participants were also shown a series of pairs of alternatives, each combining interventions and morbidity, mortality and cost outcomes and declared a preference for one combination. A random utility model was developed to determine the individual’s preference for interventions and a hierarchical cluster analysis was performed to identify distinct respondent preference classes. RESULTS: On average, participants preferred more intense interventions, and preferred scenarios with fewer deaths and lower tax. The number of infections did not significantly influence respondents’ responses. We identified two broad classes of respondents: those who were mortality averse and those who were expenditure averse. Education was found to be a predictor of group membership. CONCLUSION: Overall, there was considerable support for government interventions to prevent or mitigate outbreaks of emerging infectious diseases, including those that greatly restricted individual liberties, as long as the restrictions showed a reasonable chance of reducing the adverse health effects of the outbreak.",2018 Feb 16,"['Cook, Alex R', 'Zhao, Xiahong', 'Chen, Mark I C', 'Finkelstein, Eric A']",BMJ Open,,,False
85f0fe06df221d355fc228db1495a4f940e7c9b7,PMC,Public preferences for interventions to prevent emerging infectious disease threats: a discrete choice experiment,http://dx.doi.org/10.1136/bmjopen-2017-017355,PMC5857709,29453294,CC BY-NC,"OBJECTIVE: When faced with an emergent epidemic with high mortality and morbidity potential, policy makers must decide what public health interventions to deploy at different stages of the outbreak. However, almost nothing is known about how the public view these interventions or how they trade off risks (of disease) with inconvenience (of interventions). In this paper, we aim to understand public perceptions on pandemic interventions, as well as to identify if there are any distinct respondent preference classes. DESIGN: A discrete choice experiment. SETTING: This study was fielded in Singapore between November 2012 and February 2013. PARTICIPANTS: A random sample of 500 Singapore residents aged 21 and over, including 271 women and 229 men, was analysed. OUTCOME MEASURES: Demographic information was collected from each participant. Participants were also shown a series of pairs of alternatives, each combining interventions and morbidity, mortality and cost outcomes and declared a preference for one combination. A random utility model was developed to determine the individual’s preference for interventions and a hierarchical cluster analysis was performed to identify distinct respondent preference classes. RESULTS: On average, participants preferred more intense interventions, and preferred scenarios with fewer deaths and lower tax. The number of infections did not significantly influence respondents’ responses. We identified two broad classes of respondents: those who were mortality averse and those who were expenditure averse. Education was found to be a predictor of group membership. CONCLUSION: Overall, there was considerable support for government interventions to prevent or mitigate outbreaks of emerging infectious diseases, including those that greatly restricted individual liberties, as long as the restrictions showed a reasonable chance of reducing the adverse health effects of the outbreak.",2018 Feb 16,"['Cook, Alex R', 'Zhao, Xiahong', 'Chen, Mark I C', 'Finkelstein, Eric A']",BMJ Open,,,True
0b2c383c48f644edcb7c4dcf40046bd58dd5e0f8,PMC,Targeting regenerative exosomes to myocardial infarction using cardiac homing peptide,http://dx.doi.org/10.7150/thno.20524,PMC5858505,29556361,CC BY-NC,"Rationale: Cardiac stem cell-derived exosomes have been demonstrated to promote cardiac regeneration following myocardial infarction in preclinical studies. Recent studies have used intramyocardial injection in order to concentrate exosomes in the infarct. Though effective in a research setting, this method is not clinically appealing due to its invasive nature. We propose the use of a targeting peptide, cardiac homing peptide (CHP), to target intravenously-infused exosomes to the infarcted heart. Methods: Exosomes were conjugated with CHP through a DOPE-NHS linker. Ex vivo targeting was analyzed by incubating organ sections with the CHP exosomes and analyzing with fluorescence microscopy. In vitro assays were performed on neonatal rat cardiomyocytes and H9C2 cells. For the animal study, we utilized an ischemia/reperfusion rat model. Animals were treated with either saline, scramble peptide exosomes, or CHP exosomes 24 h after surgery. Echocardiography was performed 4 h after surgery and 21 d after surgery. At 21 d, animals were sacrificed, and organs were collected for analysis. Results: By conjugating the exosomes with CHP, we demonstrate increased retention of the exosomes within heart sections ex vivo and in vitro with neonatal rat cardiomyocytes. In vitro studies showed improved viability, reduced apoptosis and increased exosome uptake when using CHP-XOs. Using an animal model of ischemia/reperfusion injury, we measured the heart function, infarct size, cellular proliferation, and angiogenesis, with improved outcomes with the CHP exosomes. Conclusions: Our results demonstrate a novel method for increasing delivery of for treatment of myocardial infarction. By targeting exosomes to the infarcted heart, there was a significant improvement in outcomes with reduced fibrosis and scar size, and increased cellular proliferation and angiogenesis.",2018 Feb 14,"['Vandergriff, Adam', 'Huang, Ke', 'Shen, Deliang', 'Hu, Shiqi', 'Hensley, Michael Taylor', 'Caranasos, Thomas G.', 'Qian, Li', 'Cheng, Ke']",Theranostics,,,True
54c7ae0162fc474c120bae00c715a30d4d118a9c,PMC,Targeting regenerative exosomes to myocardial infarction using cardiac homing peptide,http://dx.doi.org/10.7150/thno.20524,PMC5858505,29556361,CC BY-NC,"Rationale: Cardiac stem cell-derived exosomes have been demonstrated to promote cardiac regeneration following myocardial infarction in preclinical studies. Recent studies have used intramyocardial injection in order to concentrate exosomes in the infarct. Though effective in a research setting, this method is not clinically appealing due to its invasive nature. We propose the use of a targeting peptide, cardiac homing peptide (CHP), to target intravenously-infused exosomes to the infarcted heart. Methods: Exosomes were conjugated with CHP through a DOPE-NHS linker. Ex vivo targeting was analyzed by incubating organ sections with the CHP exosomes and analyzing with fluorescence microscopy. In vitro assays were performed on neonatal rat cardiomyocytes and H9C2 cells. For the animal study, we utilized an ischemia/reperfusion rat model. Animals were treated with either saline, scramble peptide exosomes, or CHP exosomes 24 h after surgery. Echocardiography was performed 4 h after surgery and 21 d after surgery. At 21 d, animals were sacrificed, and organs were collected for analysis. Results: By conjugating the exosomes with CHP, we demonstrate increased retention of the exosomes within heart sections ex vivo and in vitro with neonatal rat cardiomyocytes. In vitro studies showed improved viability, reduced apoptosis and increased exosome uptake when using CHP-XOs. Using an animal model of ischemia/reperfusion injury, we measured the heart function, infarct size, cellular proliferation, and angiogenesis, with improved outcomes with the CHP exosomes. Conclusions: Our results demonstrate a novel method for increasing delivery of for treatment of myocardial infarction. By targeting exosomes to the infarcted heart, there was a significant improvement in outcomes with reduced fibrosis and scar size, and increased cellular proliferation and angiogenesis.",2018 Feb 14,"['Vandergriff, Adam', 'Huang, Ke', 'Shen, Deliang', 'Hu, Shiqi', 'Hensley, Michael Taylor', 'Caranasos, Thomas G.', 'Qian, Li', 'Cheng, Ke']",Theranostics,,,False
9f9de51e9537bc4c203dad26bf1e99d91f2b15e8,PMC,Applications of gold nanoparticles in virus detection,http://dx.doi.org/10.7150/thno.23856,PMC5858513,29556369,CC BY-NC,"Viruses are the smallest known microbes, yet they cause the most significant losses in human health. Most of the time, the best-known cure for viruses is the innate immunological defense system of the host; otherwise, the initial prevention of viral infection is the only alternative. Therefore, diagnosis is the primary strategy toward the overarching goal of virus control and elimination. The introduction of a new class of nanoscale materials with multiple unique properties and functions has sparked a series of breakthrough applications. Gold nanoparticles (AuNPs) are widely reported to guide an impressive resurgence in biomedical and diagnostic applications. Here, we review the applications of AuNPs in virus testing and detection. The developed AuNP-based detection techniques are reported for various groups of clinically relevant viruses with a special focus on the applied types of bio-AuNP hybrid structures, virus detection targets, and assay modalities and formats. We pay particular attention to highlighting the functional role and activity of each core Au nanostructure and the resultant detection improvements in terms of sensitivity, detection range, and time. In addition, we provide a general summary of the contributions of AuNPs to the mainstream methods of virus detection, technical measures, and recommendations required in guidance toward commercial in-field applications.",2018 Feb 15,"['Draz, Mohamed Shehata', 'Shafiee, Hadi']",Theranostics,,,True
0568c55234a6ad2585fe3ac5f3c51260194af7ec,PMC,Development of a Rapid Diagnostic Test Kit to Detect IgG/IgM Antibody against Zika Virus Using Monoclonal Antibodies to the Envelope and Non-structural Protein 1 of the Virus,http://dx.doi.org/10.3347/kjp.2018.56.1.61,PMC5858665,29529852,CC BY-NC,"We developed a Rapid Diagnostic Test (RDT) kit for detecting IgG/IgM antibodies against Zika virus (ZIKV) using monoclonal antibodies to the envelope (E) and non-structural protein 1 (NS1) of ZIKV. These proteins were produced using baculovirus expression vector with Sf9 cells. Monoclonal antibodies J2G7 to NS1 and J5E1 to E protein were selected and conjugated with colloidal gold to produce the Zika IgG/IgM RDT kit (Zika RDT). Comparisons with ELISA, plaque reduction neutralization test (PRNT), and PCR were done to investigate the analytical sensitivity of Zika RDT, which resulted in 100% identical results. Sensitivity and specificity of Zika RDT in a field test was determined using positive and negative samples from Brazil and Korea. The diagnostic accuracy of Zika RDT was fairly high; sensitivity and specificity for IgG was 99.0 and 99.3%, respectively, while for IgM it was 96.7 and 98.7%, respectively. Cross reaction with dengue virus was evaluated using anti-Dengue Mixed Titer Performance Panel (PVD201), in which the Zika RDT showed cross-reactions with DENV in 16.7% and 5.6% in IgG and IgM, respectively. Cross reactions were not observed with West Nile, yellow fever, and hepatitis C virus infected sera. Zika RDT kit is very simple to use, rapid to assay, and very sensitive, and highly specific. Therefore, it would serve as a choice of method for point-of-care diagnosis and large scale surveys of ZIKV infection under clinical or field conditions worldwide in endemic areas.",2018 Feb 28,"['Kim, Yeong Hoon', 'Lee, Jihoo', 'Kim, Young-Eun', 'Chong, Chom-Kyu', 'Pinchemel, Yanaihara', 'Reisdörfer, Francis', 'Coelho, Joyce Brito', 'Dias, Ronaldo Ferreira', 'Bae, Pan Kee', 'Gusmão, Zuinara Pereira Maia', 'Ahn, Hye-Jin', 'Nam, Ho-Woo']",Korean J Parasitol,,,True
f77d9d6d6d7730a6a554319266051a8b1e36970b,PMC,MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity,http://dx.doi.org/10.1073/pnas.1718769115,PMC5866576,29507189,CC BY-NC-ND,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. Although MERS-CoV infection is ubiquitous in dromedaries across Africa as well as in the Arabian Peninsula, zoonotic disease appears confined to the Arabian Peninsula. MERS-CoVs from Africa have hitherto been poorly studied. We genetically and phenotypically characterized MERS-CoV from dromedaries sampled in Morocco, Burkina Faso, Nigeria, and Ethiopia. Viruses from Africa (clade C) are phylogenetically distinct from contemporary viruses from the Arabian Peninsula (clades A and B) but remain antigenically similar in microneutralization tests. Viruses from West (Nigeria, Burkina Faso) and North (Morocco) Africa form a subclade, C1, that shares clade-defining genetic signatures including deletions in the accessory gene ORF4b. Compared with human and camel MERS-CoV from Saudi Arabia, virus isolates from Burkina Faso (BF785) and Nigeria (Nig1657) had lower virus replication competence in Calu-3 cells and in ex vivo cultures of human bronchus and lung. BF785 replicated to lower titer in lungs of human DPP4-transduced mice. A reverse genetics-derived recombinant MERS-CoV (EMC) lacking ORF4b elicited higher type I and III IFN responses than the isogenic EMC virus in Calu-3 cells. However, ORF4b deletions may not be the major determinant of the reduced replication competence of BF785 and Nig1657. Genetic and phenotypic differences in West African viruses may be relevant to zoonotic potential. There is an urgent need for studies of MERS-CoV at the animal–human interface.",2018 Mar 20,"['Chu, Daniel K. W.', 'Hui, Kenrie P. Y.', 'Perera, Ranawaka A. P. M.', 'Miguel, Eve', 'Niemeyer, Daniela', 'Zhao, Jincun', 'Channappanavar, Rudragouda', 'Dudas, Gytis', 'Oladipo, Jamiu O.', 'Traoré, Amadou', 'Fassi-Fihri, Ouafaa', 'Ali, Abraham', 'Demissié, Getnet F.', 'Muth, Doreen', 'Chan, Michael C. W.', 'Nicholls, John M.', 'Meyerholz, David K.', 'Kuranga, Sulyman A.', 'Mamo, Gezahegne', 'Zhou, Ziqi', 'So, Ray T. Y.', 'Hemida, Maged G.', 'Webby, Richard J.', 'Roger, Francois', 'Rambaut, Andrew', 'Poon, Leo L. M.', 'Perlman, Stanley', 'Drosten, Christian', 'Chevalier, Veronique', 'Peiris, Malik']",Proc Natl Acad Sci U S A,,,True
1bf18631b9c161ea2834b3d7c8ea42875319d18c,PMC,MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity,http://dx.doi.org/10.1073/pnas.1718769115,PMC5866576,29507189,CC BY-NC-ND,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. Although MERS-CoV infection is ubiquitous in dromedaries across Africa as well as in the Arabian Peninsula, zoonotic disease appears confined to the Arabian Peninsula. MERS-CoVs from Africa have hitherto been poorly studied. We genetically and phenotypically characterized MERS-CoV from dromedaries sampled in Morocco, Burkina Faso, Nigeria, and Ethiopia. Viruses from Africa (clade C) are phylogenetically distinct from contemporary viruses from the Arabian Peninsula (clades A and B) but remain antigenically similar in microneutralization tests. Viruses from West (Nigeria, Burkina Faso) and North (Morocco) Africa form a subclade, C1, that shares clade-defining genetic signatures including deletions in the accessory gene ORF4b. Compared with human and camel MERS-CoV from Saudi Arabia, virus isolates from Burkina Faso (BF785) and Nigeria (Nig1657) had lower virus replication competence in Calu-3 cells and in ex vivo cultures of human bronchus and lung. BF785 replicated to lower titer in lungs of human DPP4-transduced mice. A reverse genetics-derived recombinant MERS-CoV (EMC) lacking ORF4b elicited higher type I and III IFN responses than the isogenic EMC virus in Calu-3 cells. However, ORF4b deletions may not be the major determinant of the reduced replication competence of BF785 and Nig1657. Genetic and phenotypic differences in West African viruses may be relevant to zoonotic potential. There is an urgent need for studies of MERS-CoV at the animal–human interface.",2018 Mar 20,"['Chu, Daniel K. W.', 'Hui, Kenrie P. Y.', 'Perera, Ranawaka A. P. M.', 'Miguel, Eve', 'Niemeyer, Daniela', 'Zhao, Jincun', 'Channappanavar, Rudragouda', 'Dudas, Gytis', 'Oladipo, Jamiu O.', 'Traoré, Amadou', 'Fassi-Fihri, Ouafaa', 'Ali, Abraham', 'Demissié, Getnet F.', 'Muth, Doreen', 'Chan, Michael C. W.', 'Nicholls, John M.', 'Meyerholz, David K.', 'Kuranga, Sulyman A.', 'Mamo, Gezahegne', 'Zhou, Ziqi', 'So, Ray T. Y.', 'Hemida, Maged G.', 'Webby, Richard J.', 'Roger, Francois', 'Rambaut, Andrew', 'Poon, Leo L. M.', 'Perlman, Stanley', 'Drosten, Christian', 'Chevalier, Veronique', 'Peiris, Malik']",Proc Natl Acad Sci U S A,,,True
3e3f1f1b1f7f02523bc38fc9a0c321d1ccc9e1b8,PMC,Zinc Deficiency‐Like Syndrome in Fleckvieh Calves: Clinical and Pathological Findings and Differentiation from Bovine Hereditary Zinc Deficiency,http://dx.doi.org/10.1111/jvim.15040,PMC5866964,29424482,CC BY-NC,"BACKGROUND: Zinc deficiency‐like (ZDL) syndrome is an inherited defect of Fleckvieh calves, with striking similarity to bovine hereditary zinc deficiency (BHZD). However, the causative mutation in a phospholipase D4 encoding gene (PLD4) shows no connection to zinc metabolism. OBJECTIVES: To describe clinical signs, laboratory variables, and pathological findings of ZDL syndrome and their utility to differentiate ZDL from BHZD and infectious diseases with similar phenotype. ANIMALS: Nine hospitalized calves with crusting dermatitis and confirmed mutation in PLD4 and medical records from 25 calves with crusting dermatitis or suspected zinc deficiency. METHODS: Prospective and retrospective case series. RESULTS: The 9 calves (age: 5–53 weeks) displayed a moderate to severe crusting dermatitis mainly on the head, ventrum, and joints. Respiratory and digestive tract inflammations were frequently observed. Zinc supplementation did not lead to remission of clinical signs in 4 calves. Laboratory variables revealed slight anemia in 8 calves, hypoalbuminemia in 6 calves, but reduced serum zinc concentrations in only 3 calves. Mucosal erosions/ulcerations were present in 7 calves and thymus atrophy or reduced thymic weights in 8 calves. Histologically, skin lesions were indistinguishable from BHZD. Retrospective analysis of medical records revealed the presence of this phenotype since 1988 and pedigree analysis revealed a common ancestor of several affected calves. CONCLUSIONS AND CLINICAL IMPORTANCE: ZDL syndrome should be suspected in Fleckvieh calves with crusting dermatitis together with diarrhea or respiratory tract inflammations without response to oral zinc supplementation. Definite diagnosis requires molecular genetic confirmation of the PLD4 mutation.",2018 Feb 9 Mar-Apr,"['Langenmayer, M.C.', 'Jung, S.', 'Majzoub‐Altweck, M.', 'Trefz, F.M.', 'Seifert, C.', 'Knubben‐Schweizer, G.', 'Fries, R.', 'Hermanns, W.', 'Gollnick, N.S.']",J Vet Intern Med,,,True
51a25686ff156fa8b99d72204eb04a10079a0a74,PMC,"10th Annual European College of Equine Internal Medicine Congress: 2—4 November, 2017",http://dx.doi.org/10.1111/jvim.15044,PMC5867002,,CC BY-NC,,2018 Feb 22 Mar-Apr,,J Vet Intern Med,,,True
a4edf4ce073f52028af8e88621a26288d9af4c02,PMC,Using an epidemiological framework and bovine spongiform encephalopathy investigation questionnaire to investigate suspect bovine spongiform encephalopathy cases: an example from a bovine spongiform encephalopathy case in Ireland in 2015,http://dx.doi.org/10.1136/vr.104148,PMC5870463,29122979,CC BY-NC,"In several EU member states, bovine spongiform encephalopathy (BSE) cases have been identified in cattle born after the reinforced ban (BARB cases), for reasons that are not entirely clear. Epidemiological investigation of these cases has proved challenging. The European Food Safety Authority recently recommended the collection of a predefined set of epidemiological data from BSE suspects and confirmed BSE cases to aid future investigations. In this study, we present an epidemiological framework and BSE investigation questionnaire to aid the investigation of suspect BSE cases, and illustrate its application during the investigation of a BSE case in Ireland in 2015. It is recommended that the framework and questionnaire are used concurrently: the framework provides structure and focus, whereas the questionnaire (with 135 questions) aids data collection. The framework focuses on confirmation and discrimination, estimating the date and location of exposure, and determining the method/source of exposure. The BSE case in Ireland in 2015 was a BARB case born in 2010. It was identified with classical BSE at an authorised knackery as part of Ireland’s targeted active surveillance programme for BSE. No definitive source of infection with the BSE agent could be attributed in this case.",2018 Feb 10,"['O’Connor, Jarlath T', 'Byrne, Justin P', 'More, Simon J', 'Blake, Martin', 'McGrath, Guy', 'Tratalos, Jamie A', 'Mcelroy, Maire C', 'Kiernan, Paul', 'Canty, Mary J', 'O’Brien-Lynch, Chris', 'Griffin, John M']",Vet Rec,,,True
287b5c7a2b4796e938d9b73516fad5fbbda3ecc8,PMC,Using an epidemiological framework and bovine spongiform encephalopathy investigation questionnaire to investigate suspect bovine spongiform encephalopathy cases: an example from a bovine spongiform encephalopathy case in Ireland in 2015,http://dx.doi.org/10.1136/vr.104148,PMC5870463,29122979,CC BY-NC,"In several EU member states, bovine spongiform encephalopathy (BSE) cases have been identified in cattle born after the reinforced ban (BARB cases), for reasons that are not entirely clear. Epidemiological investigation of these cases has proved challenging. The European Food Safety Authority recently recommended the collection of a predefined set of epidemiological data from BSE suspects and confirmed BSE cases to aid future investigations. In this study, we present an epidemiological framework and BSE investigation questionnaire to aid the investigation of suspect BSE cases, and illustrate its application during the investigation of a BSE case in Ireland in 2015. It is recommended that the framework and questionnaire are used concurrently: the framework provides structure and focus, whereas the questionnaire (with 135 questions) aids data collection. The framework focuses on confirmation and discrimination, estimating the date and location of exposure, and determining the method/source of exposure. The BSE case in Ireland in 2015 was a BARB case born in 2010. It was identified with classical BSE at an authorised knackery as part of Ireland’s targeted active surveillance programme for BSE. No definitive source of infection with the BSE agent could be attributed in this case.",2018 Feb 10,"['O’Connor, Jarlath T', 'Byrne, Justin P', 'More, Simon J', 'Blake, Martin', 'McGrath, Guy', 'Tratalos, Jamie A', 'Mcelroy, Maire C', 'Kiernan, Paul', 'Canty, Mary J', 'O’Brien-Lynch, Chris', 'Griffin, John M']",Vet Rec,,,False
313690d6cc7481e946a4b42a6337be19182f19da,PMC,Using an epidemiological framework and bovine spongiform encephalopathy investigation questionnaire to investigate suspect bovine spongiform encephalopathy cases: an example from a bovine spongiform encephalopathy case in Ireland in 2015,http://dx.doi.org/10.1136/vr.104148,PMC5870463,29122979,CC BY-NC,"In several EU member states, bovine spongiform encephalopathy (BSE) cases have been identified in cattle born after the reinforced ban (BARB cases), for reasons that are not entirely clear. Epidemiological investigation of these cases has proved challenging. The European Food Safety Authority recently recommended the collection of a predefined set of epidemiological data from BSE suspects and confirmed BSE cases to aid future investigations. In this study, we present an epidemiological framework and BSE investigation questionnaire to aid the investigation of suspect BSE cases, and illustrate its application during the investigation of a BSE case in Ireland in 2015. It is recommended that the framework and questionnaire are used concurrently: the framework provides structure and focus, whereas the questionnaire (with 135 questions) aids data collection. The framework focuses on confirmation and discrimination, estimating the date and location of exposure, and determining the method/source of exposure. The BSE case in Ireland in 2015 was a BARB case born in 2010. It was identified with classical BSE at an authorised knackery as part of Ireland’s targeted active surveillance programme for BSE. No definitive source of infection with the BSE agent could be attributed in this case.",2018 Feb 10,"['O’Connor, Jarlath T', 'Byrne, Justin P', 'More, Simon J', 'Blake, Martin', 'McGrath, Guy', 'Tratalos, Jamie A', 'Mcelroy, Maire C', 'Kiernan, Paul', 'Canty, Mary J', 'O’Brien-Lynch, Chris', 'Griffin, John M']",Vet Rec,,,False
a32757c9e2857202acf9b238a2004a533670affc,PMC,Rapid and sensitive insulated isothermal PCR for point-of-need feline leukaemia virus detection,http://dx.doi.org/10.1177/1098612X17712847,PMC5871024,28589743,CC BY-NC,"OBJECTIVES: Feline leukaemia virus (FeLV), a gamma retrovirus, causes diseases of the feline haematopoietic system that are invariably fatal. Rapid and accurate testing at the point-of-need (PON) supports prevention of virus spread and management of clinical disease. This study evaluated the performance of an insulated isothermal PCR (iiPCR) that detects proviral DNA, and a reverse transcription (RT)-iiPCR that detects both viral RNA and proviral DNA, for FeLV detection at the PON. METHODS: Mycoplasma haemofelis, feline coronavirus, feline herpesvirus, feline calicivirus and feline immunodeficiency virus were used to test analytical specificity. In vitro transcribed RNA, artificial plasmid, FeLV strain American Type Culture Collection VR-719 and a clinical FeLV isolate were used in the analytical sensitivity assays. A retrospective study including 116 clinical plasma and serum samples that had been tested with virus isolation, real-time PCR and ELISA, and a prospective study including 150 clinical plasma and serum samples were implemented to evaluate the clinical performances of the iiPCR-based methods for FeLV detection. RESULTS: Ninety-five percent assay limit of detection was calculated to be 16 RNA and five DNA copies for the RT-iiPCR, and six DNA copies for the iiPCR. Both reactions had analytical sensitivity comparable to a reference real-time PCR (qPCR) and did not detect five non-target feline pathogens. The clinical performance of the RT-iiPCR and iiPCR had 98.82% agreement (kappa[κ] = 0.97) and 100% agreement (κ = 1.0), respectively, with the qPCR (n = 85). The agreement between an automatic nucleic extraction/RT-iiPCR system and virus isolation to detect FeLV in plasma or serum was 95.69% (κ = 0.95) and 98.67% (κ = 0.85) in a retrospective (n = 116) and a prospective (n = 150) study, respectively. CONCLUSIONS AND RELEVANCE: These results suggested that both RT-iiPCR and iiPCR assays can serve as reliable tools for PON FeLV detection.",2018 Apr 7,"['Wilkes, Rebecca P', 'Anis, Eman', 'Dunbar, Dawn', 'Lee, Pei-Yu A', 'Tsai, Yun-Long', 'Lee, Fu-Chun', 'Chang, Hsiao-Fen G', 'Wang, Hwa-Tang T', 'Graham, Elizabeth M']",J Feline Med Surg,,,True
11f3cdbb678b326042e1d0c38887a34a2177ddfe,PMC,Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis,http://dx.doi.org/10.1177/1098612X17729626,PMC5871025,28901812,CC BY-NC,"OBJECTIVES: The safety and efficacy of the 3C-like protease inhibitor GC376 was tested on a cohort of client-owned cats with various forms of feline infectious peritonitis (FIP). METHODS: Twenty cats from 3.3–82 months of age (mean 10.4 months) with various forms of FIP were accepted into a field trial. Fourteen cats presented with wet or dry-to-wet FIP and six cats presented with dry FIP. GC376 was administered subcutaneously every 12 h at a dose of 15 mg/kg. Cats with neurologic signs were excluded from the study. RESULTS: Nineteen of 20 cats treated with GC376 regained outward health within 2 weeks of initial treatment. However, disease signs recurred 1–7 weeks after primary treatment and relapses and new cases were ultimately treated for a minimum of 12 weeks. Relapses no longer responsive to treatment occurred in 13 of these 19 cats within 1–7 weeks of initial or repeat treatment(s). Severe neurologic disease occurred in 8/13 cats that failed treatment and five cats had recurrences of abdominal lesions. At the time of writing, seven cats were in disease remission. Five kittens aged 3.3–4.4 months with wet FIP were treated for 12 weeks and have been in disease remission after stopping treatment and at the time of writing for 5–14 months (mean 11.2 months). A sixth kitten was in remission for 10 weeks after 12 weeks of treatment, relapsed and is responding to a second round of GC376. The seventh was a 6.8-year-old cat with only mesenteric lymph node involvement that went into remission after three relapses that required progressively longer repeat treatments over a 10 month period. Side effects of treatment included transient stinging upon injection and occasional foci of subcutaneous fibrosis and hair loss. There was retarded development and abnormal eruption of permanent teeth in cats treated before 16–18 weeks of age. CONCLUSIONS AND RELEVANCE: GC376 showed promise in treating cats with certain presentations of FIP and has opened the door to targeted antiviral drug therapy.",2018 Apr 13,"['Pedersen, Niels C', 'Kim, Yunjeong', 'Liu, Hongwei', 'Galasiti Kankanamalage, Anushka C', 'Eckstrand, Chrissy', 'Groutas, William C', 'Bannasch, Michael', 'Meadows, Juliana M', 'Chang, Kyeong-Ok']",J Feline Med Surg,,,True
40b2b0e3d2cf519723d858a138e77a26a70f460f,PMC,"Impact of Ebola experiences and risk perceptions on mental health in Sierra Leone, July 2015",http://dx.doi.org/10.1136/bmjgh-2017-000471,PMC5873549,29607096,CC BY-NC,"BACKGROUND: The mental health impact of the 2014–2016 Ebola epidemic has been described among survivors, family members and healthcare workers, but little is known about its impact on the general population of affected countries. We assessed symptoms of anxiety, depression and post-traumatic stress disorder (PTSD) in the general population in Sierra Leone after over a year of outbreak response. METHODS: We administered a cross-sectional survey in July 2015 to a national sample of 3564 consenting participants selected through multistaged cluster sampling. Symptoms of anxiety and depression were measured by Patient Health Questionnaire-4. PTSD symptoms were measured by six items from the Impact of Events Scale-revised. Relationships among Ebola experience, perceived Ebola threat and mental health symptoms were examined through binary logistic regression. RESULTS: Prevalence of any anxiety-depression symptom was 48% (95% CI 46.8% to 50.0%), and of any PTSD symptom 76% (95% CI 75.0% to 77.8%). In addition, 6% (95% CI 5.4% to 7.0%) met the clinical cut-off for anxiety-depression, 27% (95% CI 25.8% to 28.8%) met levels of clinical concern for PTSD and 16% (95% CI 14.7% to 17.1%) met levels of probable PTSD diagnosis. Factors associated with higher reporting of any symptoms in bivariate analysis included region of residence, experiences with Ebola and perceived Ebola threat. Knowing someone quarantined for Ebola was independently associated with anxiety-depression (adjusted OR (AOR) 2.3, 95% CI 1.7 to 2.9) and PTSD (AOR 2.095% CI 1.5 to 2.8) symptoms. Perceiving Ebola as a threat was independently associated with anxiety-depression (AOR 1.69 95% CI 1.44 to 1.98) and PTSD (AOR 1.86 95% CI 1.56 to 2.21) symptoms. CONCLUSION: Symptoms of PTSD and anxiety-depression were common after one year of Ebola response; psychosocial support may be needed for people with Ebola-related experiences. Preventing, detecting, and responding to mental health conditions should be an important component of global health security efforts.",2018 Mar 17,"['Jalloh, Mohamed F', 'Li, Wenshu', 'Bunnell, Rebecca E', 'Ethier, Kathleen A', 'O’Leary, Ann', 'Hageman, Kathy M', 'Sengeh, Paul', 'Jalloh, Mohammad B', 'Morgan, Oliver', 'Hersey, Sara', 'Marston, Barbara J', 'Dafae, Foday', 'Redd, John T']",BMJ Glob Health,,,True
c77bacdacff014d8295b8716d57899ed6ab624b9,PMC,"Impact of Ebola experiences and risk perceptions on mental health in Sierra Leone, July 2015",http://dx.doi.org/10.1136/bmjgh-2017-000471,PMC5873549,29607096,CC BY-NC,"BACKGROUND: The mental health impact of the 2014–2016 Ebola epidemic has been described among survivors, family members and healthcare workers, but little is known about its impact on the general population of affected countries. We assessed symptoms of anxiety, depression and post-traumatic stress disorder (PTSD) in the general population in Sierra Leone after over a year of outbreak response. METHODS: We administered a cross-sectional survey in July 2015 to a national sample of 3564 consenting participants selected through multistaged cluster sampling. Symptoms of anxiety and depression were measured by Patient Health Questionnaire-4. PTSD symptoms were measured by six items from the Impact of Events Scale-revised. Relationships among Ebola experience, perceived Ebola threat and mental health symptoms were examined through binary logistic regression. RESULTS: Prevalence of any anxiety-depression symptom was 48% (95% CI 46.8% to 50.0%), and of any PTSD symptom 76% (95% CI 75.0% to 77.8%). In addition, 6% (95% CI 5.4% to 7.0%) met the clinical cut-off for anxiety-depression, 27% (95% CI 25.8% to 28.8%) met levels of clinical concern for PTSD and 16% (95% CI 14.7% to 17.1%) met levels of probable PTSD diagnosis. Factors associated with higher reporting of any symptoms in bivariate analysis included region of residence, experiences with Ebola and perceived Ebola threat. Knowing someone quarantined for Ebola was independently associated with anxiety-depression (adjusted OR (AOR) 2.3, 95% CI 1.7 to 2.9) and PTSD (AOR 2.095% CI 1.5 to 2.8) symptoms. Perceiving Ebola as a threat was independently associated with anxiety-depression (AOR 1.69 95% CI 1.44 to 1.98) and PTSD (AOR 1.86 95% CI 1.56 to 2.21) symptoms. CONCLUSION: Symptoms of PTSD and anxiety-depression were common after one year of Ebola response; psychosocial support may be needed for people with Ebola-related experiences. Preventing, detecting, and responding to mental health conditions should be an important component of global health security efforts.",2018 Mar 17,"['Jalloh, Mohamed F', 'Li, Wenshu', 'Bunnell, Rebecca E', 'Ethier, Kathleen A', 'O’Leary, Ann', 'Hageman, Kathy M', 'Sengeh, Paul', 'Jalloh, Mohammad B', 'Morgan, Oliver', 'Hersey, Sara', 'Marston, Barbara J', 'Dafae, Foday', 'Redd, John T']",BMJ Glob Health,,,False
9305dcf034dfe834775ad84358b90ae50092b829,PMC,Small-cell Lung Cancer Presenting as Fatal Pulmonary Hemorrhage,http://dx.doi.org/10.1515/med-2018-0009,PMC5874507,29607415,CC BY-NC-ND,"Small-cell lung cancer (SCLC) is a lung cancer histological subtype unusual in its favorable response to cytotoxic chemotherapy. Life-threatening manifestations at presentation are rarely reported and should be an important clinical concern. We report a case of a 63-year-old man presenting with rapid-onset refractory severe thrombocytopenia, development of massive hemoptysis, and death from respiratory failure. This case provides clinicians a reference for this unusual presentation and carries clinical implications for managing SCLC patients.",2018 Mar 21,"['Lim, Jun Hyeok', 'Ryu, Jeong-Seon', 'Cho, Sang Yong', 'Kim, Hyun-Jung', 'Jeon, Sang Hoon', 'Kim, Jung Soo', 'Nam, Hae-Seong', 'Cho, Jae Hwa', 'Kwak, Seung Min', 'Lee, Hong Lyeol']",Open Med (Wars),,,True
48545476b719bbb0efc851c4bb4da881b8244cc2,PMC,Randomised controlled trial of rhinothermy for treatment of the common cold: a feasibility study,http://dx.doi.org/10.1136/bmjopen-2017-019350,PMC5875674,29593018,CC BY-NC,"OBJECTIVE: To determine the feasibility of a randomised controlled trial (RCT) of rhinothermy for the common cold. DESIGN: Open label, randomised, controlled feasibility study. SETTING: Single-centre research institute in New Zealand recruiting participants from the community. PARTICIPANTS: 30 adult participants with symptoms of a common cold, presenting within 48 hours of the onset of symptoms. INTERVENTIONS: Participants were randomly assigned 2:1 to receive either 35 L/min of 100% humidified air at 41°C via high flow nasal cannulae, 2 hours per day for up to 5 days (rhinothermy), or vitamin C 250 mg daily for 5 days (control). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of screened candidates who were randomised. Secondary outcomes included: proportion of randomised participants who completed the study; modified Jackson scores from randomisation to 10 days after initiation of randomised regimen; time until feeling ‘a lot better’ compared with study entry; time until resolution of symptoms or symptom score at 10 days postrandomisation; proportion of organisms identified by PCR analysis of nasal swabs taken at baseline; the patterns of use of the rhinothermy device; estimated adherence of the control group; and rhinothermy device tolerability. RESULTS: In all 30/79 (38%, 95% CI 27% to 50%) of potential participants screened for eligibility were randomised. Rhinothermy was well tolerated, and all randomised participants completed the study (100%, 95% CI 88% to 100%). The reduction from baseline in the modified Jackson score was greater with rhinothermy compared with control at days 2, 3, 4, 5 and 6, with the maximum difference at day 4 (−6.4, 95% CI −9.4 to −3.3). The substantial clinical benefit threshold for modified Jackson score was a 5-unit change. CONCLUSIONS: This study shows that an RCT of rhinothermy compared with low-dose vitamin C in the treatment of the common cold is feasible. TRIAL REGISTRATION NUMBER: ACTRN12616000470493; Results.",2018 Mar 27,"['van de Hei, Susanne', 'McKinstry, Steven', 'Bardsley, George', 'Weatherall, Mark', 'Beasley, Richard', 'Fingleton, James']",BMJ Open,,,True
4c8bac1e65d1fd2effec0b45c143a97cef99aebd,PMC,Randomised controlled trial of rhinothermy for treatment of the common cold: a feasibility study,http://dx.doi.org/10.1136/bmjopen-2017-019350,PMC5875674,29593018,CC BY-NC,"OBJECTIVE: To determine the feasibility of a randomised controlled trial (RCT) of rhinothermy for the common cold. DESIGN: Open label, randomised, controlled feasibility study. SETTING: Single-centre research institute in New Zealand recruiting participants from the community. PARTICIPANTS: 30 adult participants with symptoms of a common cold, presenting within 48 hours of the onset of symptoms. INTERVENTIONS: Participants were randomly assigned 2:1 to receive either 35 L/min of 100% humidified air at 41°C via high flow nasal cannulae, 2 hours per day for up to 5 days (rhinothermy), or vitamin C 250 mg daily for 5 days (control). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of screened candidates who were randomised. Secondary outcomes included: proportion of randomised participants who completed the study; modified Jackson scores from randomisation to 10 days after initiation of randomised regimen; time until feeling ‘a lot better’ compared with study entry; time until resolution of symptoms or symptom score at 10 days postrandomisation; proportion of organisms identified by PCR analysis of nasal swabs taken at baseline; the patterns of use of the rhinothermy device; estimated adherence of the control group; and rhinothermy device tolerability. RESULTS: In all 30/79 (38%, 95% CI 27% to 50%) of potential participants screened for eligibility were randomised. Rhinothermy was well tolerated, and all randomised participants completed the study (100%, 95% CI 88% to 100%). The reduction from baseline in the modified Jackson score was greater with rhinothermy compared with control at days 2, 3, 4, 5 and 6, with the maximum difference at day 4 (−6.4, 95% CI −9.4 to −3.3). The substantial clinical benefit threshold for modified Jackson score was a 5-unit change. CONCLUSIONS: This study shows that an RCT of rhinothermy compared with low-dose vitamin C in the treatment of the common cold is feasible. TRIAL REGISTRATION NUMBER: ACTRN12616000470493; Results.",2018 Mar 27,"['van de Hei, Susanne', 'McKinstry, Steven', 'Bardsley, George', 'Weatherall, Mark', 'Beasley, Richard', 'Fingleton, James']",BMJ Open,,,True
038af1fa39ac7f1644910dbf785ce2ac48e65070,PMC,Randomised controlled trial of rhinothermy for treatment of the common cold: a feasibility study,http://dx.doi.org/10.1136/bmjopen-2017-019350,PMC5875674,29593018,CC BY-NC,"OBJECTIVE: To determine the feasibility of a randomised controlled trial (RCT) of rhinothermy for the common cold. DESIGN: Open label, randomised, controlled feasibility study. SETTING: Single-centre research institute in New Zealand recruiting participants from the community. PARTICIPANTS: 30 adult participants with symptoms of a common cold, presenting within 48 hours of the onset of symptoms. INTERVENTIONS: Participants were randomly assigned 2:1 to receive either 35 L/min of 100% humidified air at 41°C via high flow nasal cannulae, 2 hours per day for up to 5 days (rhinothermy), or vitamin C 250 mg daily for 5 days (control). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of screened candidates who were randomised. Secondary outcomes included: proportion of randomised participants who completed the study; modified Jackson scores from randomisation to 10 days after initiation of randomised regimen; time until feeling ‘a lot better’ compared with study entry; time until resolution of symptoms or symptom score at 10 days postrandomisation; proportion of organisms identified by PCR analysis of nasal swabs taken at baseline; the patterns of use of the rhinothermy device; estimated adherence of the control group; and rhinothermy device tolerability. RESULTS: In all 30/79 (38%, 95% CI 27% to 50%) of potential participants screened for eligibility were randomised. Rhinothermy was well tolerated, and all randomised participants completed the study (100%, 95% CI 88% to 100%). The reduction from baseline in the modified Jackson score was greater with rhinothermy compared with control at days 2, 3, 4, 5 and 6, with the maximum difference at day 4 (−6.4, 95% CI −9.4 to −3.3). The substantial clinical benefit threshold for modified Jackson score was a 5-unit change. CONCLUSIONS: This study shows that an RCT of rhinothermy compared with low-dose vitamin C in the treatment of the common cold is feasible. TRIAL REGISTRATION NUMBER: ACTRN12616000470493; Results.",2018 Mar 27,"['van de Hei, Susanne', 'McKinstry, Steven', 'Bardsley, George', 'Weatherall, Mark', 'Beasley, Richard', 'Fingleton, James']",BMJ Open,,,False
720e97f144701d39fcf758c33f32098f358e8764,PMC,Randomised controlled trial of rhinothermy for treatment of the common cold: a feasibility study,http://dx.doi.org/10.1136/bmjopen-2017-019350,PMC5875674,29593018,CC BY-NC,"OBJECTIVE: To determine the feasibility of a randomised controlled trial (RCT) of rhinothermy for the common cold. DESIGN: Open label, randomised, controlled feasibility study. SETTING: Single-centre research institute in New Zealand recruiting participants from the community. PARTICIPANTS: 30 adult participants with symptoms of a common cold, presenting within 48 hours of the onset of symptoms. INTERVENTIONS: Participants were randomly assigned 2:1 to receive either 35 L/min of 100% humidified air at 41°C via high flow nasal cannulae, 2 hours per day for up to 5 days (rhinothermy), or vitamin C 250 mg daily for 5 days (control). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of screened candidates who were randomised. Secondary outcomes included: proportion of randomised participants who completed the study; modified Jackson scores from randomisation to 10 days after initiation of randomised regimen; time until feeling ‘a lot better’ compared with study entry; time until resolution of symptoms or symptom score at 10 days postrandomisation; proportion of organisms identified by PCR analysis of nasal swabs taken at baseline; the patterns of use of the rhinothermy device; estimated adherence of the control group; and rhinothermy device tolerability. RESULTS: In all 30/79 (38%, 95% CI 27% to 50%) of potential participants screened for eligibility were randomised. Rhinothermy was well tolerated, and all randomised participants completed the study (100%, 95% CI 88% to 100%). The reduction from baseline in the modified Jackson score was greater with rhinothermy compared with control at days 2, 3, 4, 5 and 6, with the maximum difference at day 4 (−6.4, 95% CI −9.4 to −3.3). The substantial clinical benefit threshold for modified Jackson score was a 5-unit change. CONCLUSIONS: This study shows that an RCT of rhinothermy compared with low-dose vitamin C in the treatment of the common cold is feasible. TRIAL REGISTRATION NUMBER: ACTRN12616000470493; Results.",2018 Mar 27,"['van de Hei, Susanne', 'McKinstry, Steven', 'Bardsley, George', 'Weatherall, Mark', 'Beasley, Richard', 'Fingleton, James']",BMJ Open,,,False
9c4f25ca5cba3c28cd396f69bf49454ed15c19d4,PMC,Irreversible inactivation of ISG15 by a viral leader protease enables alternative infection detection strategies,http://dx.doi.org/10.1073/pnas.1710617115,PMC5877979,29463763,CC BY-NC-ND,"In response to viral infection, cells mount a potent inflammatory response that relies on ISG15 and ubiquitin posttranslational modifications. Many viruses use deubiquitinases and deISGylases that reverse these modifications and antagonize host signaling processes. We here reveal that the leader protease, Lb(pro), from foot-and-mouth disease virus (FMDV) targets ISG15 and to a lesser extent, ubiquitin in an unprecedented manner. Unlike canonical deISGylases that hydrolyze the isopeptide linkage after the C-terminal GlyGly motif, Lb(pro) cleaves the peptide bond preceding the GlyGly motif. Consequently, the GlyGly dipeptide remains attached to the substrate Lys, and cleaved ISG15 is rendered incompetent for reconjugation. A crystal structure of Lb(pro) bound to an engineered ISG15 suicide probe revealed the molecular basis for ISG15 proteolysis. Importantly, anti-GlyGly antibodies, developed for ubiquitin proteomics, are able to detect Lb(pro) cleavage products during viral infection. This opens avenues for infection detection of FMDV based on an immutable, host-derived epitope.",2018 Mar 6,"['Swatek, Kirby N.', 'Aumayr, Martina', 'Pruneda, Jonathan N.', 'Visser, Linda J.', 'Berryman, Stephen', 'Kueck, Anja F.', 'Geurink, Paul P.', 'Ovaa, Huib', 'van Kuppeveld, Frank J. M.', 'Tuthill, Tobias J.', 'Skern, Tim', 'Komander, David']",Proc Natl Acad Sci U S A,,,True
7680374114c808d702b43749801a6418bc371f42,PMC,Irreversible inactivation of ISG15 by a viral leader protease enables alternative infection detection strategies,http://dx.doi.org/10.1073/pnas.1710617115,PMC5877979,29463763,CC BY-NC-ND,"In response to viral infection, cells mount a potent inflammatory response that relies on ISG15 and ubiquitin posttranslational modifications. Many viruses use deubiquitinases and deISGylases that reverse these modifications and antagonize host signaling processes. We here reveal that the leader protease, Lb(pro), from foot-and-mouth disease virus (FMDV) targets ISG15 and to a lesser extent, ubiquitin in an unprecedented manner. Unlike canonical deISGylases that hydrolyze the isopeptide linkage after the C-terminal GlyGly motif, Lb(pro) cleaves the peptide bond preceding the GlyGly motif. Consequently, the GlyGly dipeptide remains attached to the substrate Lys, and cleaved ISG15 is rendered incompetent for reconjugation. A crystal structure of Lb(pro) bound to an engineered ISG15 suicide probe revealed the molecular basis for ISG15 proteolysis. Importantly, anti-GlyGly antibodies, developed for ubiquitin proteomics, are able to detect Lb(pro) cleavage products during viral infection. This opens avenues for infection detection of FMDV based on an immutable, host-derived epitope.",2018 Mar 6,"['Swatek, Kirby N.', 'Aumayr, Martina', 'Pruneda, Jonathan N.', 'Visser, Linda J.', 'Berryman, Stephen', 'Kueck, Anja F.', 'Geurink, Paul P.', 'Ovaa, Huib', 'van Kuppeveld, Frank J. M.', 'Tuthill, Tobias J.', 'Skern, Tim', 'Komander, David']",Proc Natl Acad Sci U S A,,,True
82742db34be3eee4be2483c14909b1e62e3912ae,PMC,Packaging of Rift Valley fever virus pseudoviruses and establishment of a neutralization assay method,http://dx.doi.org/10.4142/jvs.2018.19.2.200,PMC5879068,28693302,CC BY-NC,"Rift Valley fever (RVF) is an acute, febrile zoonotic disease that is caused by the RVF virus (RVFV). RVF is mainly prevalent on the Arabian Peninsula, the African continent, and several islands in the Indian Ocean near southeast Africa. RVFV has been classified by the World Organisation for Animal Health (OIE) as a category A pathogen. To avoid biological safety concerns associated with use of the pathogen in RVFV neutralization assays, the present study investigated and established an RVFV pseudovirus-based neutralization assay. This study used the human immunodeficiency virus (HIV) lentiviral packaging system and RVFV structural proteins to successfully construct RVFV pseudoviruses. Electron microscopy observation and western blotting indicated that the size, structure, and shape of the packaged pseudoviruses were notably similar to those of HIV lentiviral vectors. Infection inhibition assay results showed that an antibody against RVFV inhibited the infective ability of the RVFV pseudoviruses, and an antibody neutralization assay for RVFV detection was then established. This study has successfully established a neutralization assay based on RVFV pseudoviruses and demonstrated that this method can be used to effectively evaluate antibody neutralization.",2018 Mar 23,"['Li, Yuetao', 'Zhao, Yongkun', 'Wang, Cuiling', 'Zheng, Xuexing', 'Wang, Hualei', 'Gai, Weiwei', 'Jin, Hongli', 'Yan, Feihu', 'Qiu, Boning', 'Gao, Yuwei', 'Li, Nan', 'Yang, Songtao', 'Xia, Xianzhu']",J Vet Sci,,,True
53926518a1e7f62e23699decf28f6a0c06ed94bd,PMC,Methods and approaches to disease mechanisms using systems kinomics,http://dx.doi.org/10.1016/j.synbio.2017.12.004,PMC5884222,29911197,CC BY-NC-ND,"All cellular functions, ranging from regular cell maintenance and homeostasis, specialized functions specific to cellular types, or generating responses due to external stimulus, are mediated by proteins within the cell. Regulation of these proteins allows the cell to alter its behavior under different circumstances. A major mechanism of protein regulation is utilizing protein kinases and phosphatases; enzymes that catalyze the transfer of phosphates between substrates [1]. Proteins involved in phosphate signaling are well studied and include kinases and phosphatases that catalyze opposing reactions regulating both structure and function of the cell. Kinomics is the study of kinases, phosphatases and their targets, and has been used to study the functional changes in numerous diseases and infectious diseases with aims to delineate the cellular functions affected. Identifying the phosphate signaling pathways changed by certain diseases or infections can lead to novel therapeutic targets. However, a daunting 518 putative protein kinase genes have been identified [2], indicating that this protein family is very large and complex. Identifying which enzymes are specific to a particular disease can be a laborious task. In this review, we will provide information on large-scale systems biology methodologies that allow global screening of the kinome to more efficiently identify which kinase pathways are pertinent for further study.",2017 Dec 18,"['Berard, Alicia', 'Kroeker, Andrea', 'McQueen, Peter', 'Coombs, Kevin M.']",Synth Syst Biotechnol,,,False
89767ba998659a73d2be1534cfaacdff2fbc0488,PMC,Translational profiling of B cells infected with the Epstein-Barr virus reveals 5′ leader ribosome recruitment through upstream open reading frames,http://dx.doi.org/10.1093/nar/gky129,PMC5887285,29529302,CC BY-NC,"The Epstein-Barr virus (EBV) genome encodes several hundred transcripts. We have used ribosome profiling to characterize viral translation in infected cells and map new translation initiation sites. We show here that EBV transcripts are translated with highly variable efficiency, owing to variable transcription and translation rates, variable ribosome recruitment to the leader region and coverage by monosomes versus polysomes. Some transcripts were hardly translated, others mainly carried monosomes, showed ribosome accumulation in leader regions and most likely represent non-coding RNAs. A similar process was visible for a subset of lytic genes including the key transactivators BZLF1 and BRLF1 in cells infected with weakly replicating EBV strains. This suggests that ribosome trapping, particularly in the leader region, represents a new checkpoint for the repression of lytic replication. We could identify 25 upstream open reading frames (uORFs) located upstream of coding transcripts that displayed 5′ leader ribosome trapping, six of which were located in the leader region shared by many latent transcripts. These uORFs repressed viral translation and are likely to play an important role in the regulation of EBV translation.",2018 Apr 6,"['Bencun, Maja', 'Klinke, Olaf', 'Hotz-Wagenblatt, Agnes', 'Klaus, Severina', 'Tsai, Ming-Han', 'Poirey, Remy', 'Delecluse, Henri-Jacques']",Nucleic Acids Res,,,True
219fb67386566e8bd98da17b591ae91ffc1f2b0d,PMC,Translational profiling of B cells infected with the Epstein-Barr virus reveals 5′ leader ribosome recruitment through upstream open reading frames,http://dx.doi.org/10.1093/nar/gky129,PMC5887285,29529302,CC BY-NC,"The Epstein-Barr virus (EBV) genome encodes several hundred transcripts. We have used ribosome profiling to characterize viral translation in infected cells and map new translation initiation sites. We show here that EBV transcripts are translated with highly variable efficiency, owing to variable transcription and translation rates, variable ribosome recruitment to the leader region and coverage by monosomes versus polysomes. Some transcripts were hardly translated, others mainly carried monosomes, showed ribosome accumulation in leader regions and most likely represent non-coding RNAs. A similar process was visible for a subset of lytic genes including the key transactivators BZLF1 and BRLF1 in cells infected with weakly replicating EBV strains. This suggests that ribosome trapping, particularly in the leader region, represents a new checkpoint for the repression of lytic replication. We could identify 25 upstream open reading frames (uORFs) located upstream of coding transcripts that displayed 5′ leader ribosome trapping, six of which were located in the leader region shared by many latent transcripts. These uORFs repressed viral translation and are likely to play an important role in the regulation of EBV translation.",2018 Apr 6,"['Bencun, Maja', 'Klinke, Olaf', 'Hotz-Wagenblatt, Agnes', 'Klaus, Severina', 'Tsai, Ming-Han', 'Poirey, Remy', 'Delecluse, Henri-Jacques']",Nucleic Acids Res,,,True
3ffe5f150d7f8fe18d126f3c5035ed9425f9f4b6,PMC,Network perturbation analysis of gene transcriptional profiles reveals protein targets and mechanism of action of drugs and influenza A viral infection,http://dx.doi.org/10.1093/nar/gkx1314,PMC5887474,29325153,CC BY-NC,"Genome-wide transcriptional profiling provides a global view of cellular state and how this state changes under different treatments (e.g. drugs) or conditions (e.g. healthy and diseased). Here, we present ProTINA (Protein Target Inference by Network Analysis), a network perturbation analysis method for inferring protein targets of compounds from gene transcriptional profiles. ProTINA uses a dynamic model of the cell-type specific protein–gene transcriptional regulation to infer network perturbations from steady state and time-series differential gene expression profiles. A candidate protein target is scored based on the gene network's dysregulation, including enhancement and attenuation of transcriptional regulatory activity of the protein on its downstream genes, caused by drug treatments. For benchmark datasets from three drug treatment studies, ProTINA was able to provide highly accurate protein target predictions and to reveal the mechanism of action of compounds with high sensitivity and specificity. Further, an application of ProTINA to gene expression profiles of influenza A viral infection led to new insights of the early events in the infection.",2018 Apr 6,"['Noh, Heeju', 'Shoemaker, Jason E', 'Gunawan, Rudiyanto']",Nucleic Acids Res,,,True
68e2c47647afe4bf0237d9f17bb7787738fc8663,PMC,"Cameroonian fruit bats harbor divergent viruses, including rotavirus H, bastroviruses, and picobirnaviruses using an alternative genetic code",http://dx.doi.org/10.1093/ve/vey008,PMC5888411,29644096,CC BY-NC,"Most human emerging infectious diseases originate from wildlife and bats are a major reservoir of viruses, a few of which have been highly pathogenic to humans. In some regions of Cameroon, bats are hunted and eaten as a delicacy. This close proximity between human and bats provides ample opportunity for zoonotic events. To elucidate the viral diversity of Cameroonian fruit bats, we collected and metagenomically screened eighty-seven fecal samples of Eidolon helvum and Epomophorus gambianus fruit bats. The results showed a plethora of known and novel viruses. Phylogenetic analyses of the eleven gene segments of the first complete bat rotavirus H genome, showed clearly separated clusters of human, porcine, and bat rotavirus H strains, not indicating any recent interspecies transmission events. Additionally, we identified and analyzed a bat bastrovirus genome (a novel group of recently described viruses, related to astroviruses and hepatitis E viruses), confirming their recombinant nature, and provide further evidence of additional recombination events among bat bastroviruses. Interestingly, picobirnavirus-like RNA-dependent RNA polymerase gene segments were identified using an alternative mitochondrial genetic code, and further principal component analyses suggested that they may have a similar lifestyle to mitoviruses, a group of virus-like elements known to infect the mitochondria of fungi. Although identified bat coronavirus, parvovirus, and cyclovirus strains belong to established genera, most of the identified partitiviruses and densoviruses constitute putative novel genera in their respective families. Finally, the results of the phage community analyses of these bats indicate a very diverse geographically distinct bat phage population, probably reflecting different diets and gut bacterial ecosystems.",2018 Mar 30,"['Yinda, Claude Kwe', 'Ghogomu, Stephen Mbigha', 'Conceição-Neto, Nádia', 'Beller, Leen', 'Deboutte, Ward', 'Vanhulle, Emiel', 'Maes, Piet', 'Van Ranst, Marc', 'Matthijnssens, Jelle']",Virus Evol,,,True
f3725ca2fdaeaaf188c63878e4c6263408e52aa2,PMC,Quantification of Torque Teno Virus and Epstein-Barr Virus Is of Limited Value for Predicting the Net State of Immunosuppression After Lung Transplantation,http://dx.doi.org/10.1093/ofid/ofy050,PMC5888719,29644247,CC BY-NC-ND,"BACKGROUND: Major hurdles for survival after lung transplantation are rejections and infectious complications. Adequate methods for monitoring immune suppression status are lacking. Here, we evaluated quantification of torque teno virus (TTV) and Epstein-Barr virus (EBV) as biomarkers for defining the net state of immunosuppression in lung-transplanted patients. METHODS: This prospective single-center study included 98 patients followed for 2 years after transplantation. Bacterial infections, fungal infections, viral respiratory infections (VRTI), cytomegalovirus (CMV) viremia, and acute rejections, as well as TTV and EBV levels, were monitored. RESULTS: The levels of torque teno virus DNA increased rapidly after transplantation, likely due to immunosuppressive treatment. A modest increase in levels of Epstein-Barr virus DNA was also observed after transplantation. There were no associations between either TTV or EBV and infectious events or acute rejection, respectively, during follow-up. When Tacrolimus was the main immunosuppressive treatment, TTV DNA levels were significantly elevated 6–24 months after transplantation as compared with Cyclosporine treatment. CONCLUSIONS: Although replication of TTV, but not EBV, appears to reflect the functionality of the immune system, depending on the type of immunosuppressive treatment, quantification of TTV or EBV as biomarkers has limited potential for defining the net state of immune suppression.",2018 Mar 6,"['Nordén, Rickard', 'Magnusson, Jesper', 'Lundin, Anna', 'Tang, Ka-Wei', 'Nilsson, Staffan', 'Lindh, Magnus', 'Andersson, Lars-Magnus', 'Riise, Gerdt C', 'Westin, Johan']",Open Forum Infect Dis,,,True
8d4a2fb48616bae57771c62a5bcbaf86e08b8276,PMC,"Behaviors, movements, and transmission of droplet-mediated respiratory diseases during transcontinental airline flights",http://dx.doi.org/10.1073/pnas.1711611115,PMC5889623,29555754,CC BY-NC-ND,"With over 3 billion airline passengers annually, the inflight transmission of infectious diseases is an important global health concern. Over a dozen cases of inflight transmission of serious infections have been documented, and air travel can serve as a conduit for the rapid spread of newly emerging infections and pandemics. Despite sensational media stories and anecdotes, the risks of transmission of respiratory viruses in an airplane cabin are unknown. Movements of passengers and crew may facilitate disease transmission. On 10 transcontinental US flights, we chronicled behaviors and movements of individuals in the economy cabin on single-aisle aircraft. We simulated transmission during flight based on these data. Our results indicate there is low probability of direct transmission to passengers not seated in close proximity to an infectious passenger. This data-driven, dynamic network transmission model of droplet-mediated respiratory disease is unique. To measure the true pathogen burden, our team collected 229 environmental samples during the flights. Although eight flights were during Influenza season, all qPCR assays for 18 common respiratory viruses were negative.",2018 Apr 3,"['Hertzberg, Vicki Stover', 'Weiss, Howard', 'Elon, Lisa', 'Si, Wenpei', 'Norris, Sharon L.', None]",Proc Natl Acad Sci U S A,,,True
1e2d677d52fc513fc7207329be88bc5d08ea9965,PMC,"Behaviors, movements, and transmission of droplet-mediated respiratory diseases during transcontinental airline flights",http://dx.doi.org/10.1073/pnas.1711611115,PMC5889623,29555754,CC BY-NC-ND,"With over 3 billion airline passengers annually, the inflight transmission of infectious diseases is an important global health concern. Over a dozen cases of inflight transmission of serious infections have been documented, and air travel can serve as a conduit for the rapid spread of newly emerging infections and pandemics. Despite sensational media stories and anecdotes, the risks of transmission of respiratory viruses in an airplane cabin are unknown. Movements of passengers and crew may facilitate disease transmission. On 10 transcontinental US flights, we chronicled behaviors and movements of individuals in the economy cabin on single-aisle aircraft. We simulated transmission during flight based on these data. Our results indicate there is low probability of direct transmission to passengers not seated in close proximity to an infectious passenger. This data-driven, dynamic network transmission model of droplet-mediated respiratory disease is unique. To measure the true pathogen burden, our team collected 229 environmental samples during the flights. Although eight flights were during Influenza season, all qPCR assays for 18 common respiratory viruses were negative.",2018 Apr 3,"['Hertzberg, Vicki Stover', 'Weiss, Howard', 'Elon, Lisa', 'Si, Wenpei', 'Norris, Sharon L.', None]",Proc Natl Acad Sci U S A,,,True
3bed29e225d41a6617ee40c5bc70c0574388079a,PMC,Addressing the selectivity and toxicity of antiviral nucleosides,http://dx.doi.org/10.1177/2040206618758524,PMC5890540,29534607,CC BY-NC,"Nucleoside and nucleotide analogs have played significant roles in antiviral therapies and are valued for their impressive potency and high barrier to resistance. They have been approved for treatment of herpes simplex virus-1, HIV, HBV, HCV, and influenza, and new drugs are being developed for the treatment of RSV, Ebola, coronavirus MERS, and other emerging viruses. However, this class of compounds has also experienced a high attrition rate in clinical trials due to toxicity. In this review, we discuss the utility of different biochemical and cell-based assays and provide recommendations for assessing toxicity liability before entering animal toxicity studies.",2018 Mar 13,"Feng, Joy Y",Antivir Chem Chemother,,,True
f8540b3d4f17c2c73a9f6bf6f76b2d9350f85c46,PMC,Flexibility—Not just for yoga anymore!,http://dx.doi.org/10.1177/2040206618756788,PMC5890542,29466861,CC BY-NC,"Over the past few years, nucleosides have maintained a prominent role as one of the cornerstones of antiviral and anticancer therapeutics, and many approaches to nucleoside drug design have been pursued. One such approach involves flexibility in the sugar moiety of nucleosides, for example, in the highly successful anti-HIV and HBV drug tenofovir. In contrast, introduction of flexibility to the nucleobase scaffold has only more recently gained significance with the invention of our fleximers. The history, development, and some biological relevance for this innovative class of nucleosides are detailed herein.",2018 Feb 21,"Seley-Radtke, Katherine",Antivir Chem Chemother,,,True
097e78073b154805e74de8245008ee3f91c24af2,PMC,Nucleosides for the treatment of respiratory RNA virus infections,http://dx.doi.org/10.1177/2040206618764483,PMC5890544,29562753,CC BY-NC,"Influenza virus, respiratory syncytial virus, human metapneumovirus, parainfluenza virus, coronaviruses, and rhinoviruses are among the most common viruses causing mild seasonal colds. These RNA viruses can also cause lower respiratory tract infections leading to bronchiolitis and pneumonia. Young children, the elderly, and patients with compromised cardiac, pulmonary, or immune systems are at greatest risk for serious disease associated with these RNA virus respiratory infections. In addition, swine and avian influenza viruses, together with severe acute respiratory syndrome-associated and Middle Eastern respiratory syndrome coronaviruses, represent significant pandemic threats to the general population. In this review, we describe the current medical need resulting from respiratory infections caused by RNA viruses, which justifies drug discovery efforts to identify new therapeutic agents. The RNA polymerase of respiratory viruses represents an attractive target for nucleoside and nucleotide analogs acting as inhibitors of RNA chain synthesis. Here, we present the molecular, biochemical, and structural fundamentals of the polymerase of the four major families of RNA respiratory viruses: Orthomyxoviridae, Pneumoviridae/Paramyxoviridae, Coronaviridae, and Picornaviridae. We summarize past and current efforts to develop nucleoside and nucleotide analogs as antiviral agents against respiratory virus infections. This includes molecules with very broad antiviral spectrum such as ribavirin and T-705 (favipiravir), and others targeting more specifically one or a few virus families. Recent advances in our understanding of the structure(s) and function(s) of respiratory virus polymerases will likely support the discovery and development of novel nucleoside analogs.",2018 Mar 21,"['Jordan, Paul C', 'Stevens, Sarah K', 'Deval, Jerome']",Antivir Chem Chemother,,,True
9555f44156bc5f2c6ac191dda2fb651501a7bd7b,PMC,Nucleoside analogs as a rich source of antiviral agents active against arthropod-borne flaviviruses,http://dx.doi.org/10.1177/2040206618761299,PMC5890575,29534608,CC BY-NC,"Nucleoside analogs represent the largest class of small molecule-based antivirals, which currently form the backbone of chemotherapy of chronic infections caused by HIV, hepatitis B or C viruses, and herpes viruses. High antiviral potency and favorable pharmacokinetics parameters make some nucleoside analogs suitable also for the treatment of acute infections caused by other medically important RNA and DNA viruses. This review summarizes available information on antiviral research of nucleoside analogs against arthropod-borne members of the genus Flavivirus within the family Flaviviridae, being primarily focused on description of nucleoside inhibitors of flaviviral RNA-dependent RNA polymerase, methyltransferase, and helicase/NTPase. Inhibitors of intracellular nucleoside synthesis and newly discovered nucleoside derivatives with high antiflavivirus potency, whose modes of action are currently not completely understood, have drawn attention. Moreover, this review highlights important challenges and complications in nucleoside analog development and suggests possible strategies to overcome these limitations.",2018 Mar 13,"['Eyer, Luděk', 'Nencka, Radim', 'de Clercq, Erik', 'Seley-Radtke, Katherine', 'Růžek, Daniel']",Antivir Chem Chemother,,,True
bd72dbca2c8c9bc8345d9e100474a7f52fc44ff8,PMC,Steroid-associated osteonecrosis animal model in rats,http://dx.doi.org/10.1016/j.jot.2018.01.003,PMC5892381,29662787,CC BY-NC-ND,"OBJECTIVE: Established preclinical disease models are essential for not only studying aetiology and/or pathophysiology of the relevant diseases but more importantly also for testing prevention and/or treatment concept(s). The present study proposed and established a detailed induction and assessment protocol for a unique and cost-effective preclinical steroid-associated osteonecrosis (SAON) in rats with pulsed injections of lipopolysaccharide (LPS) and methylprednisolone (MPS). METHODS: Sixteen 24-week-old male Sprague–Dawley rats were used to induce SAON by one intravenous injection of LPS (0.2 mg/kg) and three intraperitoneal injections of MPS (100 mg/kg) with a time interval of 24 hour, and then, MPS (40 mg/kg) was intraperitoneally injected three times a week from week 2 until sacrifice. Additional 12 rats were used as normal controls. Two and six weeks after induction, animals were scanned by metabolic dual energy X-ray absorptiometry for evaluation of tissue composition; serum was collected for bone turnover markers, Microfil perfusion was performed for angiography, the liver was collected for histopathology and bilateral femora and bilateral tibiae were collected for histological examination. RESULTS: Three rats died after LPS injection, i.e., with 15.8% (3/19) mortality. Histological evaluation showed 100% incidence of SAON at week 2. Dual energy X-ray absorptiometry showed significantly higher fat percent and lower lean mass in SAON group at week 6. Micro-computed tomography (Micro-CT) showed significant bone degradation at proximal tibia 6 weeks after SAON induction. Angiography illustrated significantly less blood vessels in the proximal tibia and significantly more leakage particles in the distal tibia 2 weeks after SAON induction. Serum amino-terminal propeptide of type I collagen and osteocalcin were significantly lower at both 2 and 6 weeks after SAON induction, and serum carboxy-terminal telopeptide was significantly lower at 6 weeks after SAON induction. Histomorphometry revealed significantly lower osteoblast surface and higher marrow fat fraction and oedema area in SAON group. Hepatic oedema appeared 2 weeks after SAON induction, and lipid accumulation appeared in the liver of SAON rats 6 weeks after SAON induction. CONCLUSION: The present study successfully induced SAON in rats with pulsed injection of LPS and MPS, which was well simulating the clinical feature and pathology. Apart from available large animal models, such as bipedal emus or quadrupedal rabbits, our current SAON small model in rats could be a cost-effective preclinical experimental model to study body metabolism, molecular mechanism of SAON and potential drugs developed for prevention or treatment of SAON. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The present study successfully induced SAON in a small animal model in rats with pulsed injection of LPS and MPS. The evaluation protocols with typical histopathologic ON features and advanced evaluation approaches to identify the metabolic disorders of SAON could be used in future rat SAON studies. The SAON rat model is a suitable and cost-effective animal model to study molecular mechanism of SAON and potential drugs developed for prevention and treatment of SAON.",2018 Feb 6,"['Zheng, Li-Zhen', 'Wang, Jia-Li', 'Kong, Ling', 'Huang, Le', 'Tian, Li', 'Pang, Qian-Qian', 'Wang, Xin-Luan', 'Qin, Ling']",J Orthop Translat,,,False
426eeb6c4a3047760cd5402f4f4771a317026f95,PMC,Assessment of the ability of V920 recombinant vesicular stomatitis-Zaire ebolavirus vaccine to replicate in relevant arthropod cell cultures and vector species,http://dx.doi.org/10.1080/21645515.2017.1412898,PMC5893201,29206076,CC BY-NC-ND,"V920, rVSVΔG-ZEBOV-GP, is a recombinant vesicular stomatitis-Zaire ebolavirus vaccine which has shown an acceptable safety profile and provides a protective immune response against Ebola virus disease (EVD) induced by Zaire ebolavirus in humans. The purpose of this study was to determine whether the V920 vaccine is capable of replicating in arthropod cell cultures of relevant vector species and of replicating in live mosquitoes. While the V920 vaccine replicated well in Vero cells, no replication was observed in Anopheles or Aedes mosquito, Culicoides biting midge, or Lutzomyia sand fly cells, nor in live Culex or Aedes mosquitoes following exposure through intrathoracic inoculation or feeding on a high-titer infectious blood meal. The insect taxa selected for use in this study represent actual and potential epidemic vectors of VSV. V920 vaccine inoculated into Cx. quinquefasciatus and Ae. aegypti mosquitoes demonstrated persistence of replication-competent virus following inoculation, consistent with the recognized biological stability of the vaccine, but no evidence for active virus replication in live mosquitoes was observed. Following administration of an infectious blood meal to Ae. aegypti and Cx. quinquefasciatus mosquitoes at a titer several log(10) PFU more concentrated than would be observed in vaccinated individuals, no infection or dissemination of V920 was observed in either mosquito species. In vitro and in vivo data gathered during this study support minimal risk of the vector-borne potential of the V920 vaccine.",2018 Jan 3,"['Bergren, Nicholas A.', 'Miller, Megan R.', 'Monath, Thomas P.', 'Kading, Rebekah C.']",Hum Vaccin Immunother,,,True
83dee742692ed551c9fcdc5d76742f44acce2057,PMC,Zoonotic origin and transmission of Middle East respiratory syndrome coronavirus in the UAE,http://dx.doi.org/10.1111/zph.12435,PMC5893383,29239118,CC BY-NC,"Since the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, there have been a number of clusters of human-to-human transmission. These cases of human-to-human transmission involve close contact and have occurred primarily in healthcare settings, and they are suspected to result from repeated zoonotic introductions. In this study, we sequenced whole MERS-CoV genomes directly from respiratory samples collected from 23 confirmed MERS cases in the United Arab Emirates (UAE). These samples included cases from three nosocomial and three household clusters. The sequences were analysed for changes and relatedness with regard to the collected epidemiological data and other available MERS-CoV genomic data. Sequence analysis supports the epidemiological data within the clusters, and further, suggests that these clusters emerged independently. To understand how and when these clusters emerged, respiratory samples were taken from dromedary camels, a known host of MERS-CoV, in the same geographic regions as the human clusters. Middle East respiratory syndrome coronavirus genomes from six virus-positive animals were sequenced, and these genomes were nearly identical to those found in human patients from corresponding regions. These data demonstrate a genetic link for each of these clusters to a camel and support the hypothesis that human MERS-CoV diversity results from multiple zoonotic introductions.",2018 May 13,"['Paden, C. R.', 'Yusof, M. F. B. M.', 'Al Hammadi, Z. M.', 'Queen, K.', 'Tao, Y.', 'Eltahir, Y. M.', 'Elsayed, E. A.', 'Marzoug, B. A.', 'Bensalah, O. K. A.', 'Khalafalla, A. I.', 'Al Mulla, M.', 'Khudhair, A.', 'Elkheir, K. A.', 'Issa, Z. B.', 'Pradeep, K.', 'Elsaleh, F. N.', 'Imambaccus, H.', 'Sasse, J.', 'Weber, S.', 'Shi, M.', 'Zhang, J.', 'Li, Y.', 'Pham, H.', 'Kim, L.', 'Hall, A. J.', 'Gerber, S. I.', 'Al Hosani, F. I.', 'Tong, S.', 'Al Muhairi, S. S. M.']",Zoonoses Public Health,,,True
f3644b5ed4c1c0fbf3e59e20f2ac8c5a88ddfd6c,PMC,"Quantitative determination of residual 1,4-dioxane in three-dimensional printed bone scaffold",http://dx.doi.org/10.1016/j.jot.2017.06.004,PMC5894362,29662792,CC BY-NC-ND,"BACKGROUND/OBJECTIVE: A novel porous scaffold poly (lactide-co-glycolide) and tricalcium phosphate (PLGA/TCP) was developed by three-dimensional printing technology for bone defect repair. As a Class 2 solvent with less severe toxicity, content of residual 1,4-dioxane in this newly developed scaffold should be rigorously controlled when it is translated to clinical use. In this study, a headspace gas chromatography-mass spectrometric (HS-GC-MS) method and related testing protocol were developed for quantitative determination of 1,4-dioxane in the PLGA/TCP composite scaffolds. METHODS: Matrix effect analysis was used to optimise the pretreatment method of the scaffolds. Then, the procedure for testing 1,4-dioxane using HS-GC-MS was set up. The accuracy, precision, and robustness of this newly developed quantitative method were also validated before quantification of 1,4-dioxane in the scaffolds with different drying procedures. RESULTS: Dimethyl formamide (DMF) was the optimal solvent for dissolving scaffolds for GC-MS with proper sensitivity and without matrix effect. Then, the optimised procedure was determined as: the scaffolds were dissolved in DMF and kept at 90°C for 40 minutes, separated on a HP-5MS column, and detected by mass spectroscopy. Recovery experiments gave 97.9–100.7% recovery for 1,4-dioxane. The linear range for 1,4-dioxane was determined as 1–40 ppm with linear correlation coefficient ≥ 0.9999. Intraday and interday precision was determined as being within relative standard deviation of below 0.68%. The passable drying procedure was related to lyophilising (−50°C, 50 Pa) the scaffolds for 2 days and drying in vacuum (50 Pa) for 7 days. CONCLUSION: This is the first quantitative method established to test 1,4-dixoane in a novel scaffold. This method was validated with good accuracy and reproducibility, and met the methodological requirements of the Guideline 9101 documented in the Chinese Pharmacopoeia 2015 Edition. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This quantitative method for determination of residual 1,4-dioxane in the novel scaffolds is a key technical method during its translation into clinical use because this method is an important and indispensable file in the enterprise standard when the porous scaffold is registered as a Class III implanted medical device for bone defect repair, which is used to guarantee the safety of the scaffolds. It is also applied to optimise the drying process of scaffolds and to monitor the quality of scaffolds in the industrialisation process. Further, this method provides references for other solvents quantitative determination in porous scaffolds or materials.",2017 Jul 17,"['Li, Ling', 'Long, Jing', 'Li, Long', 'Cao, Huijuan', 'Tang, Tingting', 'Xi, Xinghua', 'Qin, Ling', 'Lai, Yuxiao', 'Wang, Xinluan']",J Orthop Translat,,,False
b746698482bd440f4d6907df9d9119b49e618512,PMC,Epidemiological factors and worldwide pattern of Middle East respiratory syndrome coronavirus from 2013 to 2016,http://dx.doi.org/10.2147/IJGM.S160741,PMC5896642,29670390,CC BY-NC,"BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging threat to global health security with high intensity and lethality. This study was conducted to investigate epidemiological factors and patterns related to this disease. METHODS: Full details of MERS-CoV cases available on the disease outbreak news section of the World Health Organization official website from January 2013 to November 2016 were retrieved; demographic and clinical information, global distribution status, potential contacts, and probable risk factors for the mortality of laboratory-confirmed MERS-CoV cases were extracted and analyzed by following standard statistical methods. RESULTS: Details of 1,094 laboratory-confirmed cases were recorded, including 421 related deaths. Significant differences were observed in the presentation of the disease from year to year, and all studied parameters differed during the years under study (all P-values <0.05). Evaluation of the effects of various potential risk factors of the final outcome (dead/survived) revealed that two factors, namely, the morbid case being native and travel history, are significant based on a unifactorial analysis (P <0.05). From 2013 to 2016, these factors remained important. However, factors that were significant in predicting mortality varied in different years. CONCLUSION: These findings point to interesting potential dimensions in the dynamic of this disease. Furthermore, effective national and international preparedness plans and actions are essential to prevent, control, and predict such viral outbreaks; improve patient management; and ensure global health security.",2018 Apr 6,"['Aghazadeh-Attari, Javad', 'Mohebbi, Iraj', 'Mansorian, Behnam', 'Ahmadzadeh, Jamal', 'Mirza-Aghazadeh-Attari, Mohammad', 'Mobaraki, Kazhal', 'Oshnouei, Sima']",Int J Gen Med,,,True
5ea6161f1a3799d02f910658992bc4df2a1cefae,PMC,Identifying agents triggering bronchiolitis in the State of Qatar,http://dx.doi.org/10.2147/IJGM.S154424,PMC5901157,29692622,CC BY-NC,"BACKGROUND: Bronchiolitis is considered as the most frequent lower respiratory tract infection in infants and young children. This disorder is marked by acute inflammation, edema, damage of epithelial cells lining small airways, and augmentation of mucus production. OBJECTIVE: The goal of the study was to identify agents triggering bronchiolitis in the State of Qatar. MATERIALS AND METHODS: A cross-sectional retrospective study was performed at Hamad Medical Corporation, the only tertiary and academic medical center in the State of Qatar. The study included infants and young children aged 0–24 months who were admitted to our pediatric ward with diagnosis of acute bronchiolitis (2010–2012) RESULTS: Eight hundred thirty-five infants and young children met the study inclusion criteria with mean age at diagnosis of 3.61±3.56 months. Respiratory virus real-time polymerase chain reaction was performed on 769 (92.0%) of the participants. Respiratory syncytial virus (RSV) was positive in 352 (45.7%) children admitted with clinical bronchiolitis. In addition, no viruses were identified in 142 (18.4%) of those admitted, and respiratory viruses other RSV were found in 275 (35.7%) of the children. Our investigations and observations show that there has been a steady and periodic seasonal variation in the RSV rate over the study period. A seasonal trend for the RSV (detected by respiratory virus real-time polymerase chain reaction) rate was evident, showing annual peaks in the months of October, November, December, and January, with a significant test for seasonality (test statistics [T]=3.15, P=0.009). CONCLUSION: In countries with desert hot weather, bronchiolitis might affect children throughout the year. Our results suggest that the combination of date regarding uninterrupted RSV seasonality can provide guidance for health care planning and application of RSV prevention scheme, such as extending the palivizumab immunoglobulin series.",2018 Apr 10,"['Hendaus, Mohamed A', 'Alhammadi, Ahmed H', 'Chandra, Prem', 'Muneer, Eshan', 'Khalifa, Mohamed S']",Int J Gen Med,,,True
adfc269121799067d9f6d6f7894f12cceb116059,PMC,Treatment of Paraquat-Induced Lung Injury With an Anti-C5a Antibody: Potential Clinical Application*,http://dx.doi.org/10.1097/CCM.0000000000002950,PMC5908256,29293144,CC BY-NC-ND,"OBJECTIVES: Complement activation product C5a plays a critical role in systemic inflammatory response syndrome induced by viruses, bacteria, and toxic agents including paraquat poisoning. This study is to explore the efficiency of anti-C5a–based intervention on systemic inflammatory responses induced by paraquat poisoning. DESIGN: Study of cynomolgus macaque model and plasma from paraquat-poisoning patients. SETTING: Laboratory investigation. SUBJECTS: Cynomolgus macaque (n = 12) and samples of plasma from patients (n = 16). INTERVENTIONS: The neutralizing antihuman C5a antibody (IFX-1) was administered to investigate the new treatment strategy for paraquat-induced systemic inflammatory responses in cynomolgus macaque model. In addition, C5a activation in plasma of paraquat patients was blocked by IFX-1 to investigate the blockade role of anti-C5a antibody in activation of inflammatory cells. MEASUREMENTS AND MAIN RESULTS: Dysregulated complement activation and the subsequent cytokine storm were found in patients with acute lung injury and in a primate model of paraquat poisoning. Targeted inhibition of C5a by IFX-1 led to marked alleviation of systemic inflammatory responses and multiple organ damage in the primate model. In addition, blockade of C5a activity in plasma from patients completely inhibited activation of CD11b on blood granulocytes from normal donors, suggesting that IFX-1 may alleviate the excessive activation of inflammatory responses and have clinical utility for patients with acute lung injury. CONCLUSIONS: Anti-C5a antibodies such as IFX-1 may be used as effective therapeutics for treatment of those suffering from systemic inflammatory responses induced by chemical poisoning like paraquat.",2018 May 13,"['Sun, Shihui', 'Jiang, Yuting', 'Wang, Renxi', 'Liu, Chenfeng', 'Liu, Xiaoling', 'Song, Nianping', 'Guo, Yan', 'Guo, Renfeng', 'Du, Lanying', 'Jiang, Shibo', 'Li, Yan', 'Qiu, Zewu', 'Zhao, Guangyu', 'Zhou, Yusen']",Crit Care Med,,,True
17c738edd73de72b15a2ca40132e7747d38fb221,PMC,An Urgent Need for Global Preparedness against the Reemergence of “Forgotten” Infectious Diseases in Korea,http://dx.doi.org/10.3346/jkms.2018.33.e125,PMC5909102,29686596,CC BY-NC,,2018 Apr 4,"['Kim, Jung Heon', 'Bae, Wonjun', 'Kim, Jiyeon', 'Hwang, Eung Soo']",J Korean Med Sci,,,True
8d88a7096820fcfb637b56b5563868c866ec692c,PMC,"Knowledge, attitude and practice of secondary schools and university students toward Middle East Respiratory Syndrome epidemic in Saudi Arabia: A cross-sectional study",http://dx.doi.org/10.1016/j.sjbs.2016.01.032,PMC5910645,29686521,CC BY-NC-ND,"This study was aiming to investigate the knowledge, practice and attitudes of secondary school and university students toward MERS-CoV infection. This is a cross-sectional study conducted in Riyadh, Saudi Arabia. Study participants were recruited from several constituent colleges of King Saud University and secondary schools in Riyadh. Data were collected using self-administered, closed-ended questionnaires. Frequencies and proportions were computed for descriptive purposes. Chi square test was utilized to depict statistical difference between groups. Among the 1109 students who answered the questionnaires, 53.1% were male, and 46.9% were female. Level of knowledge about clinical presentation of MERS is generally similar among university and school students. The most frequently reported source of transmission is entering crowded spaces and being exposed to coughing and sneezing. Additionally, hand washing was the most commonly reported method of protection against the infection. The localized spread of MERS in Saudi Arabia and the number of fatalities associated with it might have increased public interest in understanding how to maintain proper precautionary measures both on a community and on an individual level. More emphasis should be placed on educating the student participants about preventive measures such as using tissues when sneezing and coughing and proper tissue disposal.",2018 Mar 23,"['Al-Hazmi, Ali', 'Gosadi, Ibrahim', 'Somily, Ali', 'Alsubaie, Sarah', 'Bin Saeed, Abdulaziz']",Saudi J Biol Sci,,,False
37012151cf80cbbbc5ed684c0473b06b1f48d50a,PMC,Psychiatric Findings in Suspected and Confirmed Middle East Respiratory Syndrome Patients Quarantined in Hospital: A Retrospective Chart Analysis,http://dx.doi.org/10.30773/pi.2017.10.25.1,PMC5912494,29593206,CC BY-NC,"OBJECTIVE: Little is known about the psychiatric complications or risk factors for depression in suspected or confirmed Middle East Respiratory Syndrome (MERS) patients quarantined in hospital. METHODS: A retrospective chart review was performed of all the patients admitted to the acute MERS inpatient unit at the NMC during the 2015 outbreak. RESULTS: 30 (75%) were confirmed to be MERS-CoV positive among 40 admitted cases. Among the 24 MERS survivors, 17 (70.8%) exhibited psychiatric symptoms and 10 (41.7%) received a psychiatric diagnosis and medication during their hospital stay. Suspected MERS patients did not exhibit psychiatric symptoms or receive a psychiatric diagnosis. 27 suspected or confirmed MERS patients (age 41.15±18.64, male 37.0%) completed psychological assessments. A multiple linear regression analysis revealed that the Korean National Health and Nutrition Examination Survey-Short form and the Impact of Event Scale-Revised scores were significantly positively correlated with Patient Health Questionnaire-9 scores. CONCLUSION: Our findings indicate that the acute treatment of MERS-CoV infections in quarantine had a significant impact on the patients’ mental health. Furthermore, assessment of the risk factors for depression may identify vulnerable patients who require psychiatric care and attention during hospital quarantine.",2018 Apr 30,"['Kim, Hyun-Chung', 'Yoo, So-Young', 'Lee, Bun-Hee', 'Lee, So Hee', 'Shin, Hyoung-Shik']",Psychiatry Investig,,,True
3069b74346026680f8b9d9d918edbb9ce425f809,PMC,Beneficial effects of Houttuynia cordata polysaccharides on “two-hit” acute lung injury and endotoxic fever in rats associated with anti-complementary activities,http://dx.doi.org/10.1016/j.apsb.2017.11.003,PMC5925397,29719782,CC BY-NC-ND,"Houttuynia cordata Thunb. is a traditional herb used for clearing heat and eliminating toxins, and has also been used for the treatment of severe acute respiratory syndrome (SARS). In vitro, the crude H. cordata polysaccharides (CHCP) exhibited potent anti-complementary activity through both the classical and alternative pathways by acting on components C3 and C4 of the complement system without interfering with the coagulation system. This study was to investigate the preventive effects of CHCP on acute lung injury (ALI) induced by hemorrhagic shock plus lipopolysaccharide (LPS) instillation (two-hit) and LPS-induced fever in rats. CHCP significantly attenuated pulmonary injury in the “two-hit” ALI model by reducing pulmonary edema and protein exudation in bronchoalveolar lavage fluid (BALF). In addition, it reduced the deposit of complement activation products in the lung and improved oxidant-antioxidant imbalance. Moreover, CHCP administration inhibited fever in rats, reduced the number of leukocytes and restored serum complement levels. The inhibition on the inappropriate activation of complement system by CHCP may play an important role in its beneficial effects on inflammatory diseases. The anti-complementary polysaccharides are likely to be among the key substances for the heat-clearing function of H. cordata.",2018 Mar 8,"['Lu, Yan', 'Jiang, Yun', 'Ling, Lijun', 'Zhang, Yunyi', 'Li, Hong', 'Chen, Daofeng']",Acta Pharm Sin B,,,False
cca5972b7a3a481e86305ed977183997be4194ac,PMC,Beneficial effects of Houttuynia cordata polysaccharides on “two-hit” acute lung injury and endotoxic fever in rats associated with anti-complementary activities,http://dx.doi.org/10.1016/j.apsb.2017.11.003,PMC5925397,29719782,CC BY-NC-ND,"Houttuynia cordata Thunb. is a traditional herb used for clearing heat and eliminating toxins, and has also been used for the treatment of severe acute respiratory syndrome (SARS). In vitro, the crude H. cordata polysaccharides (CHCP) exhibited potent anti-complementary activity through both the classical and alternative pathways by acting on components C3 and C4 of the complement system without interfering with the coagulation system. This study was to investigate the preventive effects of CHCP on acute lung injury (ALI) induced by hemorrhagic shock plus lipopolysaccharide (LPS) instillation (two-hit) and LPS-induced fever in rats. CHCP significantly attenuated pulmonary injury in the “two-hit” ALI model by reducing pulmonary edema and protein exudation in bronchoalveolar lavage fluid (BALF). In addition, it reduced the deposit of complement activation products in the lung and improved oxidant-antioxidant imbalance. Moreover, CHCP administration inhibited fever in rats, reduced the number of leukocytes and restored serum complement levels. The inhibition on the inappropriate activation of complement system by CHCP may play an important role in its beneficial effects on inflammatory diseases. The anti-complementary polysaccharides are likely to be among the key substances for the heat-clearing function of H. cordata.",2018 Mar 8,"['Lu, Yan', 'Jiang, Yun', 'Ling, Lijun', 'Zhang, Yunyi', 'Li, Hong', 'Chen, Daofeng']",Acta Pharm Sin B,,,False
3b4c63b2763e95674b6048d7150da0b3eca21c94,PMC,Establishment of pseudovirus infection mouse models for in vivo pharmacodynamics evaluation of filovirus entry inhibitors,http://dx.doi.org/10.1016/j.apsb.2017.08.003,PMC5925413,29719780,CC BY-NC-ND,"Filoviruses cause severe and fatal viral hemorrhagic fever in humans. Filovirus research has been extensive since the 2014 Ebola outbreak. Due to their high pathogenicity and mortality, live filoviruses require Biosafety Level-4 (BSL-4) facilities, which have restricted the development of anti-filovirus vaccines and drugs. An HIV-based pseudovirus cell infection assay is widely used for viral entry studies in BSL-2 conditions. Here, we successfully constructed nine in vitro pseudo-filovirus models covering all filovirus genera and three in vivo pseudo-filovirus-infection mouse models using Ebola virus, Marburg virus, and Lloviu virus as representative viruses. The pseudo-filovirus-infected mice showed visualizing bioluminescence in a dose-dependent manner. A bioluminescence peak in mice was reached on day 5 post-infection for Ebola virus and Marburg virus and on day 4 post-infection for Lloviu virus. Two known filovirus entry inhibitors, clomiphene and toremiphene, were used to validate the model. Collectively, our study shows that all genera of filoviruses can be well-pseudotyped and are infectious in vitro. The pseudo-filovirus-infection mouse models can be used for in vivo activity evaluation of anti-filovirus drugs. This sequential in vitro and in vivo evaluation system of filovirus entry inhibitors provides a secure and efficient platform for screening and assessing anti-filovirus agents in BSL-2 facilities.",2018 Mar 22,"['Chen, Qing', 'Tang, Ke', 'Zhang, Xiaoyu', 'Chen, Panpan', 'Guo, Ying']",Acta Pharm Sin B,,,False
ec7eb0e096ddb4117326868b33a872bebb52776b,PMC,Acute exacerbation of idiopathic pulmonary fibrosis triggered by Aspergillus empyema,http://dx.doi.org/10.1016/j.rmcr.2018.01.004,PMC5925856,29719792,CC BY-NC-ND,"Acute exacerbation (AE) is a severe and life-threatening complication of idiopathic pulmonary fibrosis (IPF). In 2016, the definition and diagnostic criteria for AE-IPF were updated by an international working group. The new definition includes any acute, clinically significant respiratory deterioration (both idiopathic and triggered events) characterized by evidence of new widespread alveolar abnormality in patients with IPF. There are no currently proven beneficial management strategies for idiopathic and triggered AE-IPF. This is the first report describing AE-IPF triggered by Aspergillus empyema, which was improved by a combination of corticosteroid, systemic antifungal therapy, local antifungal therapy, and additional pharmacological therapies. Future research may reveal optimal strategies for both idiopathic and triggered AE-IPF.",2018 Jan 31,"['Suzuki, Atsushi', 'Kimura, Tomoki', 'Kataoka, Kensuke', 'Matsuda, Toshiaki', 'Yokoyama, Toshiki', 'Mori, Yuta', 'Kondoh, Yasuhiro']",Respir Med Case Rep,,,False
3b4bdc3dce8169c30fd1f151713b1f801059c694,PMC,Protein Sequence Comparison and DNA-binding Protein Identification with Generalized PseAAC and Graphical Representation,http://dx.doi.org/10.2174/1386207321666180130100838,PMC5930480,29380690,CC BY-NC,"AIM AND OBJECTIVE: The rapid increase in the amount of protein sequence data available leads to an urgent need for novel computational algorithms to analyze and compare these sequences. This study is undertaken to develop an efficient computational approach for timely encoding protein sequences and extracting the hidden information. METHODS: Based on two physicochemical properties of amino acids, a protein primary sequence was converted into a three-letter sequence, and then a graph without loops and multiple edges and its geometric line adjacency matrix were obtained. A generalized PseAAC (pseudo amino acid composition) model was thus constructed to characterize a protein sequence numerically. RESULTS: By using the proposed mathematical descriptor of a protein sequence, similarity comparisons among β-globin proteins of 17 species and 72 spike proteins of coronaviruses were made, respectively. The resulting clusters agreed well with the established taxonomic groups. In addition, a generalized PseAAC based SVM (support vector machine) model was developed to identify DNA-binding proteins. Experiment results showed that our method performed better than DNAbinder, DNA-Prot, iDNA-Prot and enDNA-Prot by 3.29-10.44% in terms of ACC, 0.056-0.206 in terms of MCC, and 1.45-15.76% in terms of F1M. When the benchmark dataset was expanded with negative samples, the presented approach outperformed the four previous methods with improvement in the range of 2.49-19.12% in terms of ACC, 0.05-0.32 in terms of MCC, and 3.82-33.85% in terms of F1M. CONCLUSION: These results suggested that the generalized PseAAC model was very efficient for comparison and analysis of protein sequences, and very competitive in identifying DNA-binding proteins.",2018 Feb,"['Li, Chun', 'Zhao, Jialing', 'Wang, Changzhong', 'Yao, Yuhua']",Comb Chem High Throughput Screen,,,True
d255417190eeff9a19aad24ac65faff0030ce157,PMC,"Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss",http://dx.doi.org/10.1136/jmedgenet-2017-104954,PMC5931241,29453195,CC BY-NC,"Background Hereditary sensorineural hearing loss is a genetically heterogeneous disorder. Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL). Methods Whole exome sequencing and linkage analysis were performed to identify pathogenic mutation. Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism. Results We identified a cosegregating heterozygous missense mutation, c.296G>A (p.Arg99His) in the gene encoding interferon lambda receptor 1 (IFNLR1) – a protein that functions in the Jak/ STAT pathway– are associated with ADNSHL. Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and non-inflation of the swim bladder in late-stage zebrafish, which can be reversed by injection with normal Zebrafish ifnlr1 mRNA. Knockdown of ifnlr1 in zebrafish causes significant upregulation of cytokine receptor family member b4 (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3 pathway at the mRNA level. Conclusion IFNLR1 function is required in the auditory system and that IFNLR1 mutations are associated with ADNSHL. To the best of our knowledge, this is the first study implicating an interferon lambda receptor in auditory function.",2018 May 16,"['Gao, Xue', 'Yuan, Yong-Yi', 'Lin, Qiong-Fen', 'Xu, Jin-Cao', 'Wang, Wei-Qian', 'Qiao, Yue-Hua', 'Kang, Dong-Yang', 'Bai, Dan', 'Xin, Feng', 'Huang, Sha-Sha', 'Qiu, Shi-Wei', 'Guan, Li-Ping', 'Su, Yu', 'Wang, Guo-Jian', 'Han, Ming-Yu', 'Jiang, Yi', 'Liu, Han-Kui', 'Dai, Pu']",J Med Genet,,,True
7f509005d87cc72a5157572cdb79faeef2ec7774,PMC,"Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss",http://dx.doi.org/10.1136/jmedgenet-2017-104954,PMC5931241,29453195,CC BY-NC,"Background Hereditary sensorineural hearing loss is a genetically heterogeneous disorder. Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL). Methods Whole exome sequencing and linkage analysis were performed to identify pathogenic mutation. Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism. Results We identified a cosegregating heterozygous missense mutation, c.296G>A (p.Arg99His) in the gene encoding interferon lambda receptor 1 (IFNLR1) – a protein that functions in the Jak/ STAT pathway– are associated with ADNSHL. Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and non-inflation of the swim bladder in late-stage zebrafish, which can be reversed by injection with normal Zebrafish ifnlr1 mRNA. Knockdown of ifnlr1 in zebrafish causes significant upregulation of cytokine receptor family member b4 (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3 pathway at the mRNA level. Conclusion IFNLR1 function is required in the auditory system and that IFNLR1 mutations are associated with ADNSHL. To the best of our knowledge, this is the first study implicating an interferon lambda receptor in auditory function.",2018 May 16,"['Gao, Xue', 'Yuan, Yong-Yi', 'Lin, Qiong-Fen', 'Xu, Jin-Cao', 'Wang, Wei-Qian', 'Qiao, Yue-Hua', 'Kang, Dong-Yang', 'Bai, Dan', 'Xin, Feng', 'Huang, Sha-Sha', 'Qiu, Shi-Wei', 'Guan, Li-Ping', 'Su, Yu', 'Wang, Guo-Jian', 'Han, Ming-Yu', 'Jiang, Yi', 'Liu, Han-Kui', 'Dai, Pu']",J Med Genet,,,False
8cb5954efbc7ab4a0d43db196b9b58b3838945b0,PMC,Symmetric dimeric adamantanes for exploring the structure of two viroporins: influenza virus M2 and hepatitis C virus p7,http://dx.doi.org/10.2147/DDDT.S157104,PMC5933338,29750015,CC BY-NC,"BACKGROUND: Adamantane-based compounds have been identified to interfere with the ion-channel activity of viroporins and thereby inhibit viral infection. To better understand the difference in the inhibition mechanism of viroporins, we synthesized symmetric dimeric adamantane analogs of various alkyl-spacer lengths. METHODS: Symmetric dimeric adamantane derivatives were synthesized where two amantadine or rimantadine molecules were linked by various alkyl-spacers. The inhibitory activity of the compounds was studied on two viroporins: the influenza virus M2 protein, expressed in Xenopus oocytes, using the two-electrode voltage-clamp technique, and the hepatitis C virus (HCV) p7 channels for five different genotypes (1a, 1b, 2a, 3a, and 4a) expressed in HEK293 cells using whole-cell patch-clamp recording techniques. RESULTS: Upon testing on M2 protein, dimeric compounds showed significantly lower inhibitory activity relative to the monomeric amantadine. The lack of channel blockage of the dimeric amantadine and rimantadine analogs against M2 wild type and M2-S31N mutant was consistent with previously proposed drug-binding mechanisms and further confirmed that the pore-binding model is the pharmacologically relevant drug-binding model. On the other hand, these dimers showed similar potency to their respective monomeric analogs when tested on p7 protein in HCV genotypes 1a, 1b, and 4a while being 700-fold and 150-fold more potent than amantadine in genotypes 2a and 3a, respectively. An amino group appears to be important for inhibiting the ion-channel activity of p7 protein in genotype 2a, while its importance was minimal in all other genotypes. CONCLUSION: Symmetric dimeric adamantanes can be considered a prospective class of p7 inhibitors that are able to address the differences in adamantane sensitivity among the various genotypes of HCV.",2018 Apr 30,"['Mandour, Yasmine M', 'Breitinger, Ulrike', 'Ma, Chunlong', 'Wang, Jun', 'Boeckler, Frank M', 'Breitinger, Hans-Georg', 'Zlotos, Darius P']",Drug Des Devel Ther,,,True
9826361eeccaade32208880c9b1907b71bd2cf79,PMC,Towards the Application of Human Defensins as Antivirals,http://dx.doi.org/10.4062/biomolther.2017.172,PMC5933891,29310427,CC BY-NC,"Defensins are antimicrobial peptides that participate in the innate immunity of hosts. Humans constitutively and/or inducibly express α- and β-defensins, which are known for their antiviral and antibacterial activities. This review describes the application of human defensins. We discuss the extant experimental results, limited though they are, to consider the potential applicability of human defensins as antiviral agents. Given their antiviral effects, we propose that basic research be conducted on human defensins that focuses on RNA viruses, such as human immunodeficiency virus (HIV), influenza A virus (IAV), respiratory syncytial virus (RSV), and dengue virus (DENV), which are considered serious human pathogens but have posed huge challenges for vaccine development for different reasons. Concerning the prophylactic and therapeutic applications of defensins, we then discuss the applicability of human defensins as antivirals that has been demonstrated in reports using animal models. Finally, we discuss the potential adjuvant-like activity of human defensins and propose an exploration of the ‘defensin vaccine’ concept to prime the body with a controlled supply of human defensins. In sum, we suggest a conceptual framework to achieve the practical application of human defensins to combat viral infections.",2018 May 9,"['Park, Mee Sook', 'Kim, Jin Il', 'Lee, Ilseob', 'Park, Sehee', 'Bae, Joon-Yong', 'Park, Man-Seong']",Biomol Ther (Seoul),,,True
23cc9704b77903e3ec5e9ecb81ebf83b3a231c4c,PMC,Banking for health: the role of financial sector actors in investing in global health,http://dx.doi.org/10.1136/bmjgh-2017-000597,PMC5935160,29736278,CC BY-NC,"The world faces multiple health financing challenges as the global health burden evolves. Countries have set an ambitious health policy agenda for the next 15 years with prioritisation of universal health coverage under the Sustainable Development Goals. The scale of investment needed for equitable access to health services means global health is one of the key economic opportunities for decades to come. New financing partnerships with the private sector are vital. The aim of this study is to unlock additional financing sources, acknowledging the imperative to link financial returns to the providers of capital, and create profitable, sustainable financing structures. This paper outlines the global health investment opportunity exploring intersections of financial and health sector interests, and the role investment in health can play in economic development. Considering increasing demand for impact investments, the paper explores responsible financing initiatives and expansion of the global movement for sustainable capital markets. Adding an explicit health component (H) to the Environmental, Social and Governance (ESG) investment criteria, creating the ESG+H initiative, could serve as catalyst for the inclusion of health criteria into mainstream financial actors’ business practices and investment objectives. The conclusion finds that health considerations directly impact profitability of the firm and therefore should be incorporated into financial analysis. Positive assessment of health impact, at a broad societal or environmental level, as well as for a firm’s employees can become a value enhancing competitive advantage. An ESG+H framework could incorporate this into mainstream financial decision-making and into scalable investment products.",2018 May 2,"['Krech, Rüdiger', 'Kickbusch, Ilona', 'Franz, Christian', 'Wells, Nadya']",BMJ Glob Health,,,True
8bf17efaaca3885956b262ec027b83e86cc1711f,PMC,Rapid detection and differentiation of avian infectious bronchitis virus: an application of Mass genotype by melting temperature analysis in RT-qPCR using SYBR Green I,http://dx.doi.org/10.1292/jvms.17-0566,PMC5938207,29491226,CC BY-NC-ND,"A method based on Melting Temperature analysis of Hypervariable regions (HVR) of S1 gene within a RT-qPCR was developed to detect different genotypes of avian infectious bronchitis virus (IBV) and identify the Mass genotype. The method was able to rapidly identify the Mass genotype among IBV field isolates, vaccine attenuated strains and reference M41 strain in allantoic liquid and also directly in tissues. The RT-qPCR developed detected the virus in both tracheal and pulmonary samples from M41-infected or H120-infected birds, in a larger post-infection period compared to detection by standard method of virus isolation. RT-qPCR method tested provided a sensitivity and rapid approach for screening on IBV detection and Mass genotyping from IBV isolates.",2018 Apr 27,"['OKINO, Cintia Hiromi', 'MONTASSIER, Maria de Fátima Silva', 'de OLIVEIRA, Andressa Peres', 'MONTASSIER, Helio José']",J Vet Med Sci,,,True
2cfdb63ea48ecc4c871cc7d61b5f5361cfd8f287,PMC,"First report of feline bocavirus associated with severe enteritis of cat in Northeast China, 2015",http://dx.doi.org/10.1292/jvms.17-0444,PMC5938208,29459503,CC BY-NC-ND,"Feline bocavirus (FBoV) is a newly identified bocavirus of cats in the family Parvoviridae. A novel FBoV HRB2015-LDF was first identified from the cat with severe enteritis in Northeast China, with an overall positive rate of 2.78% (1/36). Phylogenetic and homologous analysis of the complete genome showed that FBoV HRB2015-LDF was clustered into the FBoV branch and closely related to other FBoVs, with 68.7–97.5% identities. And the genes of VP1, NPA and NS1 shared 70.7–97.6, 72.4–98.6 and 67.2–98.0% nucleotide identities with other FBoVs, respectively. The results suggested that the FBoVs could be divided into two distinct lineages, and the difference of nucleotide identities was >20–30% between the lineages.",2018 Apr 20,"['LIU, Chunguo', 'LIU, Fei', 'LI, Zhigang', 'QU, Liandong', 'LIU, Dafei']",J Vet Med Sci,,,True
829a94ca9817bb3e0ce0373ce733fe751cb922ec,PMC,"First report of feline bocavirus associated with severe enteritis of cat in Northeast China, 2015",http://dx.doi.org/10.1292/jvms.17-0444,PMC5938208,29459503,CC BY-NC-ND,"Feline bocavirus (FBoV) is a newly identified bocavirus of cats in the family Parvoviridae. A novel FBoV HRB2015-LDF was first identified from the cat with severe enteritis in Northeast China, with an overall positive rate of 2.78% (1/36). Phylogenetic and homologous analysis of the complete genome showed that FBoV HRB2015-LDF was clustered into the FBoV branch and closely related to other FBoVs, with 68.7–97.5% identities. And the genes of VP1, NPA and NS1 shared 70.7–97.6, 72.4–98.6 and 67.2–98.0% nucleotide identities with other FBoVs, respectively. The results suggested that the FBoVs could be divided into two distinct lineages, and the difference of nucleotide identities was >20–30% between the lineages.",2018 Apr 20,"['LIU, Chunguo', 'LIU, Fei', 'LI, Zhigang', 'QU, Liandong', 'LIU, Dafei']",J Vet Med Sci,,,False
ae1f8642745871a574c0fe8193112b06a8b07212,PMC,Polysialic acid is a cellular receptor for human adenovirus 52,http://dx.doi.org/10.1073/pnas.1716900115,PMC5939068,29674446,CC BY-NC-ND,"Human adenovirus 52 (HAdV-52) is one of only three known HAdVs equipped with both a long and a short fiber protein. While the long fiber binds to the coxsackie and adenovirus receptor, the function of the short fiber in the virus life cycle is poorly understood. Here, we show, by glycan microarray analysis and cellular studies, that the short fiber knob (SFK) of HAdV-52 recognizes long chains of α-2,8-linked polysialic acid (polySia), a large posttranslational modification of selected carrier proteins, and that HAdV-52 can use polySia as a receptor on target cells. X-ray crystallography, NMR, molecular dynamics simulation, and structure-guided mutagenesis of the SFK reveal that the nonreducing, terminal sialic acid of polySia engages the protein with direct contacts, and that specificity for polySia is achieved through subtle, transient electrostatic interactions with additional sialic acid residues. In this study, we present a previously unrecognized role for polySia as a cellular receptor for a human viral pathogen. Our detailed analysis of the determinants of specificity for this interaction has general implications for protein–carbohydrate interactions, particularly concerning highly charged glycan structures, and provides interesting dimensions on the biology and evolution of members of Human mastadenovirus G.",2018 May 1,"['Lenman, Annasara', 'Liaci, A. Manuel', 'Liu, Yan', 'Frängsmyr, Lars', 'Frank, Martin', 'Blaum, Bärbel S.', 'Chai, Wengang', 'Podgorski, Iva I.', 'Harrach, Balázs', 'Benkő, Mária', 'Feizi, Ten', 'Stehle, Thilo', 'Arnberg, Niklas']",Proc Natl Acad Sci U S A,,,True
ccdfa546c3c6de3c6a91ad713d56d320eac3e6e4,PMC,Mental health of nurses after the Fukushima complex disaster: a narrative review,http://dx.doi.org/10.1093/jrr/rry023,PMC5941163,29668971,CC BY-NC,"Work-related mental health impairment is recognized as a real problem in the context of helping responders, including health professionals, due to adverse health outcomes after a severe disaster. The Great East-Japan Earthquake, which occurred on 11 March 2011, was an unprecedented complex disaster that caused a nuclear accident at the Fukushima Daiichi Nuclear Power Plant (NPP). In addition to disaster stress and daily work, medical and health-care professionals, particularly nurses, provided counseling services to residents concerned about radiation health risks or mental health issues. This review focuses on the psychological aspects of the complex nuclear disaster, which was a combined artificial nuclear accident and natural disaster, and we investigated the psychological effects on hospital nurses associated with their experiences during the disaster. We looked at several investigations into the mental health of nurses after a nuclear disaster and in other situations. It was shown that mental health of nurses is impacted, not only after nuclear disasters but also in other circumstances. Furthermore, we noted the effects of extended periods of a heavy workload and daily life. Regarding anxiety about radiation exposure, nurses who had more knowledge of radiation tended to have better mental health, suggesting that education about the health risks of radiation exposure is important for health-care professionals. In summary, it is essential that nurses are provided with education about radiation exposure and its associated health risks, and also that there is a comprehensive approach to mental health care for nurses during the chronic phase of a disaster.",2018 Apr 13,"['Nukui, Hiroshi', 'Midorikawa, Sanae', 'Murakami, Michio', 'Maeda, Masaharu', 'Ohtsuru, Akira']",J Radiat Res,,,True
2ba882c9ddb5e9db8ebb0db536788bff66b67f14,PMC,Beyond molecular tumor heterogeneity: protein synthesis takes control,http://dx.doi.org/10.1038/s41388-018-0152-0,PMC5945578,29463861,CC BY-NC-ND,"One of the daunting challenges facing modern medicine lies in the understanding and treatment of tumor heterogeneity. Most tumors show intra-tumor heterogeneity at both genomic and proteomic levels, with marked impacts on the responses of therapeutic targets. Therapeutic target-related gene expression pathways are affected by hypoxia and cellular stress. However, the finding that targets such as eukaryotic initiation factor (eIF) 4E (and its phosphorylated form, p-eIF4E) are generally homogenously expressed throughout tumors, regardless of the presence of hypoxia or other cellular stress conditions, opens the exciting possibility that malignancies could be treated with therapies that combine targeting of eIF4E phosphorylation with immune checkpoint inhibitors or chemotherapy.",2018 Feb 21,"['Ramon y Cajal, Santiago', 'Castellvi, Josep', 'Hümmer, Stefan', 'Peg, Vicente', 'Pelletier, Jerry', 'Sonenberg, Nahum']",Oncogene,,,True
1dfb38c44ff4bd4534b37c8f42f3e18c282e66e7,PMC,Potential mechanism and drug candidates for sepsis-induced acute lung injury,http://dx.doi.org/10.3892/etm.2018.6001,PMC5952104,29805488,CC BY-NC-ND,"The present study aimed to explore the mechanisms underlying sepsis-induced acute lung injury (ALI) and identify more effective therapeutic strategies to treat it. The gene expression data set GSE10474 was downloaded and assessed to identify differentially expressed genes (DEGs). Principal component analysis, functional enrichment analysis and differential co-expression analysis of DEGs were performed. Furthermore, potential target drugs for key DEGs were assessed. A total of 209 DEGs, including 107 upregulated and 102 downregulated genes were screened. A number of DEGs, including zinc finger and BTB domain containing 17 (ZBTB17), heat shock protein 90 kDa β, member 1 (HSP90B1) and major histocompatibility complex, class II, DR α were identified. Furthermore, gene ontology terms including antigen processing and presentation, glycerophospholipid metabolism, transcriptional misregulation in cancer, thyroid hormone synthesis and pathways associated with diseases, such as asthma were identified. In addition, a differential co-expression network containing ubiquitin-conjugating enzyme E2 D4, putative and tubulin, γ complex associated protein 3 was constructed. Furthermore, a number of gene-drug interactions, including between HSP90B1 and adenosine-5′-diphosphate and radicicol, were identified. Therefore, DEGs, including ZBTB17 and HSP90B1, may be important in the pathogenesis of sepsis-induced ALI. Furthermore, drugs including adenosine-5′-diphosphate may be novel drug candidates to treat patients with ALI.",2018 Jun 28,"['Xu, Chenyuan', 'Guo, Zhengqiang', 'Zhao, Chuncheng', 'Zhang, Xufeng', 'Wang, Zheng']",Exp Ther Med,,,True
b8991fb0bcc563dc28c736e05639bc604f611e84,PMC,Community-Acquired Respiratory Paramyxovirus Infection After Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience,http://dx.doi.org/10.1093/ofid/ofy077,PMC5952916,29780847,CC BY-NC-ND,"BACKGROUND: Paramyxoviruses include respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (MPV), which may cause significant respiratory tract infectious disease (RTID) and mortality after allogeneic hematopoietic cell transplantation (HCT). However, clinical data regarding frequency and outcome are scarce. METHODS: We identified all paramyxovirus RTIDs in allogeneic HCT recipients diagnosed by multiplex polymerase chain reaction between 2010 and 2014. Baseline characteristics of patients, treatment, and outcome of each episode were analyzed; ie, moderate, severe, and very severe immunodeficiency (verySID) according to HCT ≤6 months, T- or B-cell depletion ≤3 months, graft-versus-host disease, neutropenia, lymphopenia, or hypo-gammaglobulinemia. RESULTS: One hundred three RTID episodes in 66 patients were identified (PIV 47% [48 of 103], RSV 32% [33 of 103], MPV 21% [22 of 103]). Episodes occurred in 85% (87 of 103) at >100 days post-HCT. Lower RTID accounted for 36% (37 of 103). Thirty-nine percent (40 of 103) of RTID episodes required hospitalization and more frequently affected patients with lower RTID. Six percent progressed from upper to lower RTID. Overall mortality was 6% and did not differ between paramyxoviruses. Sixty-one percent (63 of 103) of episodes occurred in patients with SID, and 20.2% (19 of 63) of episodes occurred in patients with verySID. Oral ribavirin plus intravenous immunoglobulin was administered in 38% (39 of 103) of RTIDs, preferably for RSV or MPV (P ≤ .001) and for SID patients (P = .001). Patients with verySID frequently progressed to lower RTID (P = .075), required intensive care unit transfer, and showed higher mortality. CONCLUSION: Paramyxovirus RTID remains a major concern in allogeneic HCT patients fulfilling SID and verySID, emphasizing that efficacious and safe antiviral treatments are urgently needed.",2018 Apr 12,"['Spahr, Yasmin', 'Tschudin-Sutter, Sarah', 'Baettig, Veronika', 'Compagno, Francesca', 'Tamm, Michael', 'Halter, Jörg', 'Gerull, Sabine', 'Passweg, Jakob', 'Hirsch, Hans H', 'Khanna, Nina']",Open Forum Infect Dis,,,True
4a3701d8545be96ceb7d7b0625ca1702b3de2634,PMC,Characterization of respiratory infection viruses in hospitalized children from Naples province in Southern Italy,http://dx.doi.org/10.3892/etm.2018.6061,PMC5958661,29805499,CC BY-NC-ND,"Most acute respiratory infections (ARIs) in children are due to viral etiology, and represent an important cause of mortality and morbidity in children <5 years old in developing countries. The pathogens that cause ARIs vary geographically and by season, and viruses serve a major role. In the present study, the distribution of the seven respiratory viruses that are more prevalent in Southern European countries were retrospectively analyzed in a Southern Italy Hospital, that centralizes pediatric diseases from the Naples province. Viruses were categorized by a FilmArray Respiratory Panel, and demonstrated no substantial differences in sex, age and seasonal viruses distribution. However, all the investigated viruses had a higher detection rate in the surrounding municipalities than in the metropolitan area of Naples. In recent years, the association between air pollution and respiratory infections has become an increasing public health concern. The data in this study support this association in the surrounding areas of Naples extensively contaminated by environmental toxic agents. In these areas, characterization of the epidemiology of ARIs is required to implement a prevention and control program.",2018 Jun 13,"['Botti, Chiara', 'Micillo, Alberto', 'Ricci, Giuseppe', 'Russo, Adolfo', 'Denisco, Alberto', 'Cantile, Monica', 'Scognamiglio, Giosuè', 'De Rosa, Antonio', 'Botti, Gerardo']",Exp Ther Med,,,True
17c135abc3c6a212ba22ae3d3750e4a396933022,PMC,Computer-aided design of amino acid-based therapeutics: a review,http://dx.doi.org/10.2147/DDDT.S159767,PMC5958949,29795978,CC BY-NC,"During the last two decades, the pharmaceutical industry has progressed from detecting small molecules to designing biologic-based therapeutics. Amino acid-based drugs are a group of biologic-based therapeutics that can effectively combat the diseases caused by drug resistance or molecular deficiency. Computational techniques play a key role to design and develop the amino acid-based therapeutics such as proteins, peptides and peptidomimetics. In this study, it was attempted to discuss the various elements for computational design of amino acid-based therapeutics. Protein design seeks to identify the properties of amino acid sequences that fold to predetermined structures with desirable structural and functional characteristics. Peptide drugs occupy a middle space between proteins and small molecules and it is hoped that they can target “undruggable” intracellular protein–protein interactions. Peptidomimetics, the compounds that mimic the biologic characteristics of peptides, present refined pharmacokinetic properties compared to the original peptides. Here, the elaborated techniques that are developed to characterize the amino acid sequences consistent with a specific structure and allow protein design are discussed. Moreover, the key principles and recent advances in currently introduced computational techniques for rational peptide design are spotlighted. The most advanced computational techniques developed to design novel peptidomimetics are also summarized.",2018 May 14,"['Farhadi, Tayebeh', 'Hashemian, Seyed MohammadReza']",Drug Des Devel Ther,,,True
e2173589087169565c3aab50650c965bd545124d,PMC,Severe outcomes associated with respiratory viruses in newborns and infants: a prospective viral surveillance study in Jordan,http://dx.doi.org/10.1136/bmjopen-2018-021898,PMC5961648,29780032,CC BY-NC,"OBJECTIVE: To assess virus-specific hospitalisation rates, risk factors for illness severity and seasonal trends in children hospitalised with acute respiratory infections (ARI). DESIGN: Prospective cohort study. SETTING: A government hospital serving low-income and middle-income population in Amman, Jordan. PARTICIPANTS: Children under 2 years of age hospitalised with fever and/or respiratory symptoms (n=3168) from 16 March 2010 to 31 March 2013. Children with chemotherapy-associated neutropenia and newborns who had never been discharged after birth were excluded from the study. OUTCOME MEASURES: Hospitalisation rates and markers of illness severity: admission to intensive care unit (ICU), mechanical ventilation (MV), oxygen therapy, length of stay (LOS) and death. RESULTS: Of the 3168 subjects, 2581 (82%) had at least one respiratory virus detected, with respiratory syncytial virus (RSV) being the most predominant pathogen isolated. During admission, 1013 (32%) received oxygen therapy, 284 (9%) were admitted to ICU, 111 (4%) were placed on MV and 31 (1%) children died. Oxygen therapy was higher in RSV-only subjects compared with human rhinovirus-only (42%vs29%, p<0.001), adenovirus-only (42%vs21%, p<0.001) and human parainfluenza virus-only (42%vs23%, p<0.001) subjects. The presence of an underlying medical condition was associated with oxygen therapy (adjusted OR (aOR) 1.95, 95% CI 1.49 to 2.56), ICU admission (aOR 2.51, 95% CI 1.71 to 3.68), MV (aOR 1.91, 95% CI 1.11 to 3.28) and longer LOS (aOR1.71, 95% CI 1.37 to 2.13). Similarly, younger age was associated with oxygen therapy (0.23, 95% CI 0.17 to 0.31), ICU admission (aOR 0.47, 95% CI 0.30 to 0.74), MV (0.28, 95% CI 0.15 to 0.53) and longer LOS (aOR 0.47, 95% CI 0.38 to 0.59). Pneumonia was strongly associated with longer LOS (aOR 2.07, 95% CI 1.65 to 2.60), oxygen therapy (aOR 2.94, 95% CI 2.22 to 3.89), ICU admission (aOR 3.12, 95% CI 2.16 to 4.50) and MV (aOR 3.33, 95% CI 1.85 to 6.00). Virus-specific hospitalisation rates ranged from 0.5 to 10.5 per 1000 children. CONCLUSION: Respiratory viruses are associated with severe illness in Jordanian children hospitalised with ARI. Prevention strategies such as extended breast feeding, increased access to palivizumab and RSV vaccine development could help decrease hospitalisation rates and illness severity, particularly in young children with underlying medical conditions.",2018 May 20,"['Khuri-Bulos, Najwa', 'Lawrence, Lindsey', 'Piya, Bhinnata', 'Wang, Li', 'Fonnesbeck, Christopher', 'Faouri, Samir', 'Shehabi, Asem', 'Vermund, Sten H', 'Williams, John V', 'Halasa, Natasha B']",BMJ Open,,,True
57b3f365b56a5db10967e1e3f16ade5a85eb296d,PMC,Severe outcomes associated with respiratory viruses in newborns and infants: a prospective viral surveillance study in Jordan,http://dx.doi.org/10.1136/bmjopen-2018-021898,PMC5961648,29780032,CC BY-NC,"OBJECTIVE: To assess virus-specific hospitalisation rates, risk factors for illness severity and seasonal trends in children hospitalised with acute respiratory infections (ARI). DESIGN: Prospective cohort study. SETTING: A government hospital serving low-income and middle-income population in Amman, Jordan. PARTICIPANTS: Children under 2 years of age hospitalised with fever and/or respiratory symptoms (n=3168) from 16 March 2010 to 31 March 2013. Children with chemotherapy-associated neutropenia and newborns who had never been discharged after birth were excluded from the study. OUTCOME MEASURES: Hospitalisation rates and markers of illness severity: admission to intensive care unit (ICU), mechanical ventilation (MV), oxygen therapy, length of stay (LOS) and death. RESULTS: Of the 3168 subjects, 2581 (82%) had at least one respiratory virus detected, with respiratory syncytial virus (RSV) being the most predominant pathogen isolated. During admission, 1013 (32%) received oxygen therapy, 284 (9%) were admitted to ICU, 111 (4%) were placed on MV and 31 (1%) children died. Oxygen therapy was higher in RSV-only subjects compared with human rhinovirus-only (42%vs29%, p<0.001), adenovirus-only (42%vs21%, p<0.001) and human parainfluenza virus-only (42%vs23%, p<0.001) subjects. The presence of an underlying medical condition was associated with oxygen therapy (adjusted OR (aOR) 1.95, 95% CI 1.49 to 2.56), ICU admission (aOR 2.51, 95% CI 1.71 to 3.68), MV (aOR 1.91, 95% CI 1.11 to 3.28) and longer LOS (aOR1.71, 95% CI 1.37 to 2.13). Similarly, younger age was associated with oxygen therapy (0.23, 95% CI 0.17 to 0.31), ICU admission (aOR 0.47, 95% CI 0.30 to 0.74), MV (0.28, 95% CI 0.15 to 0.53) and longer LOS (aOR 0.47, 95% CI 0.38 to 0.59). Pneumonia was strongly associated with longer LOS (aOR 2.07, 95% CI 1.65 to 2.60), oxygen therapy (aOR 2.94, 95% CI 2.22 to 3.89), ICU admission (aOR 3.12, 95% CI 2.16 to 4.50) and MV (aOR 3.33, 95% CI 1.85 to 6.00). Virus-specific hospitalisation rates ranged from 0.5 to 10.5 per 1000 children. CONCLUSION: Respiratory viruses are associated with severe illness in Jordanian children hospitalised with ARI. Prevention strategies such as extended breast feeding, increased access to palivizumab and RSV vaccine development could help decrease hospitalisation rates and illness severity, particularly in young children with underlying medical conditions.",2018 May 20,"['Khuri-Bulos, Najwa', 'Lawrence, Lindsey', 'Piya, Bhinnata', 'Wang, Li', 'Fonnesbeck, Christopher', 'Faouri, Samir', 'Shehabi, Asem', 'Vermund, Sten H', 'Williams, John V', 'Halasa, Natasha B']",BMJ Open,,,True
c6ae0b53c5d55d791e999185cd5cd1a986c2eef6,PMC,Severe outcomes associated with respiratory viruses in newborns and infants: a prospective viral surveillance study in Jordan,http://dx.doi.org/10.1136/bmjopen-2018-021898,PMC5961648,29780032,CC BY-NC,"OBJECTIVE: To assess virus-specific hospitalisation rates, risk factors for illness severity and seasonal trends in children hospitalised with acute respiratory infections (ARI). DESIGN: Prospective cohort study. SETTING: A government hospital serving low-income and middle-income population in Amman, Jordan. PARTICIPANTS: Children under 2 years of age hospitalised with fever and/or respiratory symptoms (n=3168) from 16 March 2010 to 31 March 2013. Children with chemotherapy-associated neutropenia and newborns who had never been discharged after birth were excluded from the study. OUTCOME MEASURES: Hospitalisation rates and markers of illness severity: admission to intensive care unit (ICU), mechanical ventilation (MV), oxygen therapy, length of stay (LOS) and death. RESULTS: Of the 3168 subjects, 2581 (82%) had at least one respiratory virus detected, with respiratory syncytial virus (RSV) being the most predominant pathogen isolated. During admission, 1013 (32%) received oxygen therapy, 284 (9%) were admitted to ICU, 111 (4%) were placed on MV and 31 (1%) children died. Oxygen therapy was higher in RSV-only subjects compared with human rhinovirus-only (42%vs29%, p<0.001), adenovirus-only (42%vs21%, p<0.001) and human parainfluenza virus-only (42%vs23%, p<0.001) subjects. The presence of an underlying medical condition was associated with oxygen therapy (adjusted OR (aOR) 1.95, 95% CI 1.49 to 2.56), ICU admission (aOR 2.51, 95% CI 1.71 to 3.68), MV (aOR 1.91, 95% CI 1.11 to 3.28) and longer LOS (aOR1.71, 95% CI 1.37 to 2.13). Similarly, younger age was associated with oxygen therapy (0.23, 95% CI 0.17 to 0.31), ICU admission (aOR 0.47, 95% CI 0.30 to 0.74), MV (0.28, 95% CI 0.15 to 0.53) and longer LOS (aOR 0.47, 95% CI 0.38 to 0.59). Pneumonia was strongly associated with longer LOS (aOR 2.07, 95% CI 1.65 to 2.60), oxygen therapy (aOR 2.94, 95% CI 2.22 to 3.89), ICU admission (aOR 3.12, 95% CI 2.16 to 4.50) and MV (aOR 3.33, 95% CI 1.85 to 6.00). Virus-specific hospitalisation rates ranged from 0.5 to 10.5 per 1000 children. CONCLUSION: Respiratory viruses are associated with severe illness in Jordanian children hospitalised with ARI. Prevention strategies such as extended breast feeding, increased access to palivizumab and RSV vaccine development could help decrease hospitalisation rates and illness severity, particularly in young children with underlying medical conditions.",2018 May 20,"['Khuri-Bulos, Najwa', 'Lawrence, Lindsey', 'Piya, Bhinnata', 'Wang, Li', 'Fonnesbeck, Christopher', 'Faouri, Samir', 'Shehabi, Asem', 'Vermund, Sten H', 'Williams, John V', 'Halasa, Natasha B']",BMJ Open,,,False
eab7935726a93162fcc7a5566d3b410e47f23402,PMC,Evaluation of the hepatoprotective effect of combination between hinokiflavone and Glycyrrhizin against CCl(4) induced toxicity in rats,http://dx.doi.org/10.1016/j.jsps.2018.02.009,PMC5962645,29844720,CC BY-NC-ND,"Liver diseases are one of the fatal syndromes due to the vital role of the liver. Most of the effective treatment of liver conditions are of natural origin. Silymarin (SI) is the standard drug used for treatment of impaired liver functions. Two natural compounds possessing promising liver protection and with different chemical structures namely; the bioflavonoid hinokiflavone (HF) isolated from Junipers phoenicea family Cupressaceae and the sweet saponin Glycyrrhizin (GL) present in Glycyrrhiza glabra (liquorice) were selected for the current study. Since the two compounds are of different nature, they may act by different mechanisms and express synergistic effect. Combination of the two compounds using to dose levels were challenged with single doses of HF, GL and SI as well. The comparison was monitored via measuring serum biochemical parameters including, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) and total bilirubin, tissue parameters such as MDA, NP-SH and TP, histopathological study using light and electron microscope. Protective effect on kidney was also monitored histopathologically and biochemically through observing the levels of LDH, creatinine, creatinine-kinase, urea and uric acid. The combinations of HF and GL showed protective effect more than the used single doses of HF and GL alone. However, SI was superior to the used combination in the two used doses in all the measured parameters. The liver and kidney cells appearance under normal and electron microscope showed that SI treated groups showed almost normal cells with slight toxic signs. Cells from group treated with the higher doses of the combination of HF and GL showed slight signs of intoxication under light and electron microscope indicating good level of protection. Although the combination of HF and GL expressed good protection in the higher dose, however, the combination did not exceed the protective effect of SI.",2018 May 11,"['Abdel-Kader, Maged S.', 'Abulhamd, Ashraf T.', 'Hamad, Abubaker M.', 'Alanazi, Abdullah H.', 'Ali, Rizwan', 'Alqasoumi, Saleh I.']",Saudi Pharm J,,,False
eb9c9eb7292778494ca76eccd9f5646139d026de,PMC,Design and preparation of derivatives of oleanolic and glycyrrhetinic acids with cytotoxic properties,http://dx.doi.org/10.2147/DDDT.S166051,PMC5968802,29861624,CC BY-NC,"BACKGROUND: The structural modification of natural products with the aim to improve the anticancer activity is a popular current research direction. The pentacyclic triterpenoid compounds oleanolic acid (OA) and glycyrrhetinic acid (GA) are distributed widely in nature. METHODS: In this study, various oleanolic acids and glycyrrhetinic acids were designed and synthesized by using the combination principle. The in vitro anticancer activities of new OA and GA derivatives were tested by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method with SGC-7901 (gastric cancer), MCF-7 (breast cancer), Eca-109 (esophageal cancer), HeLa (cervical cancer), Hep-G2 (hepatoma cancer) and HSF (normal human skin fibroblast) cells. RESULTS AND CONCLUSION: The screening results showed that the compound 3m presented the highest inhibitory activities against SGC-7901, MCF-7 and Eca-109 cell lines with IC(50) values of 7.57±0.64 μM, 5.51±0.41 μM and 5.03±0.56 μM, respectively. In addition, this compound also showed effective inhibition of Hep-G2 cells with an IC(50) value of 4.11±0.73 μM. Moreover, compound 5b showed the strongest inhibitory activity against Hep-G2 cells with an IC(50) value of 3.74±0.18 μM and compound 3l showed strong selective inhibition of the HeLa cells with the lowest IC(50) value of 4.32±0.89 μM. A series of pharmacology experiments indicated that compound 5b could induce Hep-G2 cells autophagy and apoptosis. These compounds will expand the structural diversity of anti-cancer targets and confirm the prospects for further research.",2018 May 21,"['Wang, Rui', 'Li, Yang', 'Huai, Xu-Dong', 'Zheng, Qing-Xuan', 'Wang, Wei', 'Li, Hui-Jing', 'Huai, Qi-Yong']",Drug Des Devel Ther,,,True
b20207e964d0e06060b2b13f768412a3b78a657a,PMC,Icplm – Speakers’ Abstracts,,PMC5971196,,CC BY-NC,,2005 Dec 2,,EJIFCC,,,False
cdfa3f7c065622bfb2c811f71fc0dbae5b1a4d3d,PMC,Viral metagenomics reveals the presence of highly divergent quaranjavirus in Rhipicephalus ticks from Mozambique,http://dx.doi.org/10.1080/20008686.2018.1478585,PMC5974704,29868166,CC BY-NC,"Background: Ticks are primary vectors for many well-known disease-causing agents that affect human and animal populations globally such as tick-borne encephalitis, Crimean-Congo hemorrhagic fever and African swine fever. In this study, viral metagenomics was used to identify what viruses are present in Rhipicephalus spp. ticks collected in the Zambezi Valley of Mozambique. Methods: The RNA was amplified with sequence-independent single primer amplification (SISPA) and high-throughput sequencing was performed on the Ion Torrent platform. The generated sequences were subjected to quality check and classfied by BLAST. CodonCode aligner and SeqMan were used to assemble the sequences. Results: The majority of viral sequences showed closest sequence identity to the Orthomyxoviridae family, although viruses similar to the Parvoviridae and Coronaviridae were also identified. Nearly complete sequences of five orthomyxoviral segments (HA, NP, PB1, PB2, and PA) were obtained and these showed an amino acid identity of 32–52% to known quaranjaviruses. The sequences were most closely related to the Wellfleet Bay virus, detected and isolated from common eider during a mortality event in the USA. Conclusions: In summary, this study has identified a highly divergent virus with in the Orthomyxoviridae family associated with Rhipicephalus ticks from Mozambique. Further genetic and biological studies are needed in order to investigate potential pathogenesis of the identified orthomyxovirus.",2018 May 28,"['Cholleti, Harindranath', 'Hayer, Juliette', 'Mulandane, Fernando Chanisso', 'Falk, Kerstin', 'Fafetine, Jose', 'Berg, Mikael', 'Blomström, Anne-Lie']",Infect Ecol Epidemiol,,,True
8301fef06e9bbbde5f145096ba75e82f3e0ec160,PMC,Juglanin ameliorates UVB-induced skin carcinogenesis via anti-inflammatory and proapoptotic effects in vivo and in vitro,http://dx.doi.org/10.3892/ijmm.2018.3601,PMC5979868,29620254,CC BY-NC-ND,"Ultraviolet (UV) radiation induces skin injury, and is associated with the development and formation of melanoma, which is a highly lethal form of skin cancer. Juglanin is a natural product, which is predominantly extracted from Polygonum aviculare, and is considered a functional component among its various compounds. Juglanin has been reported to exert marked protective effects in various diseases via the inhibition of inflammation and tumor cell growth. The present study aimed to explore the effects of juglanin on human skin cancer induced by UV and to reveal the underlying molecular mechanism. In the present study, immunohistochemical analysis, western blot analysis, RT-qPCR analysis and flow cytometry assays were mainly used in vivo and/or in vitro. The results indicated that in mice, UVB exposure increased susceptibility to carcinogens, and accelerated disease pathogenesis. Conversely, juglanin was able to ameliorate this condition via inhibition of inflammation, suppression of cell proliferation and induction of apoptosis via p38/c-Jun N-terminal kinase (JNK) blockage, nuclear factor (NF)-κB inactivation and caspase stimulation in vivo. In addition, in vitro, the present study demonstrated that treatment of UVB-stimulated B16F10 melanoma cells with juglanin resulted in a dose-dependent decrease in cell viability, as well as increased apoptosis via the upregulation of caspase expression and poly (ADP-ribose) polymerase cleavage. In addition, juglanin markedly attenuated p38/JNK signaling, inactivated the phosphoinositide 3-kinase/protein kinase B pathway and suppressed UVB-induced NF-κB activation. Taken together, these results indicated the possibility of applying juglanin in combination with UVB as a potential therapeutic strategy for preventing skin cancer.",2018 Jul 29,"['Hou, Gui-Rong', 'Zeng, Kang', 'Lan, Hai-Mei', 'Wang, Qi']",Int J Mol Med,,,True
303efcb8c5b2c65281962e16039caf0a18acda73,PMC,"Steroid-associated osteonecrosis: Epidemiology, pathophysiology, animal model, prevention, and potential treatments (an overview)",http://dx.doi.org/10.1016/j.jot.2014.12.002,PMC5982361,30035041,CC BY-NC-ND,"Steroid-associated osteonecrosis (SAON) is a common orthopaedic problem caused by administration of corticosteroids prescribed for many nonorthopaedic medical conditions. We summarised different pathophysiologies of SAON which have adverse effects on multiple systems such as bone marrow stem cells (BMSCs) pool, bone matrix, cell apoptosis, lipid metabolism, and angiogenesis. Different animal models were introduced to mimic the pathophysiology of SAON and for testing the efficacy of both prevention and treatment effects of various chemical drugs, biological, and physical therapies. According to the classification of SAON, several prevention and treatment methods are applied at the different stages of SAON. For the current period, Chinese herbs may also have the potential to prevent the occurrence of SAON. In the future, genetic analysis might also be helpful to effectively predict the development of ON and provide information for personalised prevention and treatment of patients with SAON.",2015 Jan 13,"['Xie, Xin-Hui', 'Wang, Xin-Luan', 'Yang, Hui-Lin', 'Zhao, De-Wei', 'Qin, Ling']",J Orthop Translat,,,False
dd154082007ef8be3cb53089778c04ea285e6b8d,PMC,Malaria Coinfections in Febrile Pediatric Inpatients: A Hospital-Based Study From Ghana,http://dx.doi.org/10.1093/cid/cix1120,PMC5982794,29408951,CC BY-NC-ND,"BACKGROUND: The epidemiology of pediatric febrile illness is shifting in sub-Saharan Africa, but malaria remains a major cause of childhood morbidity and mortality. The present study describes causes of febrile illness in hospitalized children in Ghana and aims to determine the burden of malaria coinfections and their association with parasite densities. METHODS: In a prospective study, children (aged ≥30 days and ≤15 years) with fever ≥38.0°C were recruited after admission to the pediatric ward of a primary hospital in Ghana. Malaria parasitemia was determined and blood, stool, urine, respiratory, and cerebrospinal fluid specimens were screened for parasitic, bacterial, and viral pathogens. Associations of Plasmodium densities with other pathogens were calculated. RESULTS: From November 2013 to April 2015, 1238 children were enrolled from 4169 admissions. A clinical/microbiological diagnosis could be made in 1109/1238 (90%) patients, with Plasmodium parasitemia (n = 728/1238 [59%]) being predominant. This was followed by lower respiratory tract infections/pneumonia (n = 411/1238 [34%]; among detected pathogens most frequently Streptococcus pneumoniae, n = 192/299 [64%]), urinary tract infections (n = 218/1238 [18%]; Escherichia coli, n = 21/32 [66%]), gastrointestinal infections (n = 210 [17%]; rotavirus, n = 32/97 [33%]), and invasive bloodstream infections (n = 62 [5%]; Salmonella species, n = 47 [76%]). In Plasmodium-infected children the frequency of lower respiratory tract, gastrointestinal, and bloodstream infections increased with decreasing parasite densities. CONCLUSIONS: In a hospital setting, the likelihood of comorbidity with a nonmalarial disease is inversely correlated with increasing blood levels of malaria parasites. Hence, parasite densities provide important information as an indicator for the probability of coinfection, in particular to guide antimicrobial medication.",2018 Jun 15,"['Hogan, Benedikt', 'Eibach, Daniel', 'Krumkamp, Ralf', 'Sarpong, Nimako', 'Dekker, Denise', 'Kreuels, Benno', 'Maiga-Ascofaré, Oumou', 'Gyau Boahen, Kennedy', 'Wiafe Akenten, Charity', 'Adu-Sarkodie, Yaw', 'Owusu-Dabo, Ellis', 'May, Jürgen', None]",Clin Infect Dis,,,True
1b7520912fbd483ef60014fe0e7f0d0c2df1d07e,PMC,Malaria Coinfections in Febrile Pediatric Inpatients: A Hospital-Based Study From Ghana,http://dx.doi.org/10.1093/cid/cix1120,PMC5982794,29408951,CC BY-NC-ND,"BACKGROUND: The epidemiology of pediatric febrile illness is shifting in sub-Saharan Africa, but malaria remains a major cause of childhood morbidity and mortality. The present study describes causes of febrile illness in hospitalized children in Ghana and aims to determine the burden of malaria coinfections and their association with parasite densities. METHODS: In a prospective study, children (aged ≥30 days and ≤15 years) with fever ≥38.0°C were recruited after admission to the pediatric ward of a primary hospital in Ghana. Malaria parasitemia was determined and blood, stool, urine, respiratory, and cerebrospinal fluid specimens were screened for parasitic, bacterial, and viral pathogens. Associations of Plasmodium densities with other pathogens were calculated. RESULTS: From November 2013 to April 2015, 1238 children were enrolled from 4169 admissions. A clinical/microbiological diagnosis could be made in 1109/1238 (90%) patients, with Plasmodium parasitemia (n = 728/1238 [59%]) being predominant. This was followed by lower respiratory tract infections/pneumonia (n = 411/1238 [34%]; among detected pathogens most frequently Streptococcus pneumoniae, n = 192/299 [64%]), urinary tract infections (n = 218/1238 [18%]; Escherichia coli, n = 21/32 [66%]), gastrointestinal infections (n = 210 [17%]; rotavirus, n = 32/97 [33%]), and invasive bloodstream infections (n = 62 [5%]; Salmonella species, n = 47 [76%]). In Plasmodium-infected children the frequency of lower respiratory tract, gastrointestinal, and bloodstream infections increased with decreasing parasite densities. CONCLUSIONS: In a hospital setting, the likelihood of comorbidity with a nonmalarial disease is inversely correlated with increasing blood levels of malaria parasites. Hence, parasite densities provide important information as an indicator for the probability of coinfection, in particular to guide antimicrobial medication.",2018 Jun 15,"['Hogan, Benedikt', 'Eibach, Daniel', 'Krumkamp, Ralf', 'Sarpong, Nimako', 'Dekker, Denise', 'Kreuels, Benno', 'Maiga-Ascofaré, Oumou', 'Gyau Boahen, Kennedy', 'Wiafe Akenten, Charity', 'Adu-Sarkodie, Yaw', 'Owusu-Dabo, Ellis', 'May, Jürgen', None]",Clin Infect Dis,,,True
7961709ef8fab056a54cde0dde26db2449e60601,PMC,Malaria Coinfections in Febrile Pediatric Inpatients: A Hospital-Based Study From Ghana,http://dx.doi.org/10.1093/cid/cix1120,PMC5982794,29408951,CC BY-NC-ND,"BACKGROUND: The epidemiology of pediatric febrile illness is shifting in sub-Saharan Africa, but malaria remains a major cause of childhood morbidity and mortality. The present study describes causes of febrile illness in hospitalized children in Ghana and aims to determine the burden of malaria coinfections and their association with parasite densities. METHODS: In a prospective study, children (aged ≥30 days and ≤15 years) with fever ≥38.0°C were recruited after admission to the pediatric ward of a primary hospital in Ghana. Malaria parasitemia was determined and blood, stool, urine, respiratory, and cerebrospinal fluid specimens were screened for parasitic, bacterial, and viral pathogens. Associations of Plasmodium densities with other pathogens were calculated. RESULTS: From November 2013 to April 2015, 1238 children were enrolled from 4169 admissions. A clinical/microbiological diagnosis could be made in 1109/1238 (90%) patients, with Plasmodium parasitemia (n = 728/1238 [59%]) being predominant. This was followed by lower respiratory tract infections/pneumonia (n = 411/1238 [34%]; among detected pathogens most frequently Streptococcus pneumoniae, n = 192/299 [64%]), urinary tract infections (n = 218/1238 [18%]; Escherichia coli, n = 21/32 [66%]), gastrointestinal infections (n = 210 [17%]; rotavirus, n = 32/97 [33%]), and invasive bloodstream infections (n = 62 [5%]; Salmonella species, n = 47 [76%]). In Plasmodium-infected children the frequency of lower respiratory tract, gastrointestinal, and bloodstream infections increased with decreasing parasite densities. CONCLUSIONS: In a hospital setting, the likelihood of comorbidity with a nonmalarial disease is inversely correlated with increasing blood levels of malaria parasites. Hence, parasite densities provide important information as an indicator for the probability of coinfection, in particular to guide antimicrobial medication.",2018 Jun 15,"['Hogan, Benedikt', 'Eibach, Daniel', 'Krumkamp, Ralf', 'Sarpong, Nimako', 'Dekker, Denise', 'Kreuels, Benno', 'Maiga-Ascofaré, Oumou', 'Gyau Boahen, Kennedy', 'Wiafe Akenten, Charity', 'Adu-Sarkodie, Yaw', 'Owusu-Dabo, Ellis', 'May, Jürgen', None]",Clin Infect Dis,,,False
8c41efd40f858eb54c326bdba071085f53130d89,PMC,Malaria Coinfections in Febrile Pediatric Inpatients: A Hospital-Based Study From Ghana,http://dx.doi.org/10.1093/cid/cix1120,PMC5982794,29408951,CC BY-NC-ND,"BACKGROUND: The epidemiology of pediatric febrile illness is shifting in sub-Saharan Africa, but malaria remains a major cause of childhood morbidity and mortality. The present study describes causes of febrile illness in hospitalized children in Ghana and aims to determine the burden of malaria coinfections and their association with parasite densities. METHODS: In a prospective study, children (aged ≥30 days and ≤15 years) with fever ≥38.0°C were recruited after admission to the pediatric ward of a primary hospital in Ghana. Malaria parasitemia was determined and blood, stool, urine, respiratory, and cerebrospinal fluid specimens were screened for parasitic, bacterial, and viral pathogens. Associations of Plasmodium densities with other pathogens were calculated. RESULTS: From November 2013 to April 2015, 1238 children were enrolled from 4169 admissions. A clinical/microbiological diagnosis could be made in 1109/1238 (90%) patients, with Plasmodium parasitemia (n = 728/1238 [59%]) being predominant. This was followed by lower respiratory tract infections/pneumonia (n = 411/1238 [34%]; among detected pathogens most frequently Streptococcus pneumoniae, n = 192/299 [64%]), urinary tract infections (n = 218/1238 [18%]; Escherichia coli, n = 21/32 [66%]), gastrointestinal infections (n = 210 [17%]; rotavirus, n = 32/97 [33%]), and invasive bloodstream infections (n = 62 [5%]; Salmonella species, n = 47 [76%]). In Plasmodium-infected children the frequency of lower respiratory tract, gastrointestinal, and bloodstream infections increased with decreasing parasite densities. CONCLUSIONS: In a hospital setting, the likelihood of comorbidity with a nonmalarial disease is inversely correlated with increasing blood levels of malaria parasites. Hence, parasite densities provide important information as an indicator for the probability of coinfection, in particular to guide antimicrobial medication.",2018 Jun 15,"['Hogan, Benedikt', 'Eibach, Daniel', 'Krumkamp, Ralf', 'Sarpong, Nimako', 'Dekker, Denise', 'Kreuels, Benno', 'Maiga-Ascofaré, Oumou', 'Gyau Boahen, Kennedy', 'Wiafe Akenten, Charity', 'Adu-Sarkodie, Yaw', 'Owusu-Dabo, Ellis', 'May, Jürgen', None]",Clin Infect Dis,,,False
dcb54d30c1caa4188d4c3cdf8b41f4b50d6a22d6,PMC,Malaria Coinfections in Febrile Pediatric Inpatients: A Hospital-Based Study From Ghana,http://dx.doi.org/10.1093/cid/cix1120,PMC5982794,29408951,CC BY-NC-ND,"BACKGROUND: The epidemiology of pediatric febrile illness is shifting in sub-Saharan Africa, but malaria remains a major cause of childhood morbidity and mortality. The present study describes causes of febrile illness in hospitalized children in Ghana and aims to determine the burden of malaria coinfections and their association with parasite densities. METHODS: In a prospective study, children (aged ≥30 days and ≤15 years) with fever ≥38.0°C were recruited after admission to the pediatric ward of a primary hospital in Ghana. Malaria parasitemia was determined and blood, stool, urine, respiratory, and cerebrospinal fluid specimens were screened for parasitic, bacterial, and viral pathogens. Associations of Plasmodium densities with other pathogens were calculated. RESULTS: From November 2013 to April 2015, 1238 children were enrolled from 4169 admissions. A clinical/microbiological diagnosis could be made in 1109/1238 (90%) patients, with Plasmodium parasitemia (n = 728/1238 [59%]) being predominant. This was followed by lower respiratory tract infections/pneumonia (n = 411/1238 [34%]; among detected pathogens most frequently Streptococcus pneumoniae, n = 192/299 [64%]), urinary tract infections (n = 218/1238 [18%]; Escherichia coli, n = 21/32 [66%]), gastrointestinal infections (n = 210 [17%]; rotavirus, n = 32/97 [33%]), and invasive bloodstream infections (n = 62 [5%]; Salmonella species, n = 47 [76%]). In Plasmodium-infected children the frequency of lower respiratory tract, gastrointestinal, and bloodstream infections increased with decreasing parasite densities. CONCLUSIONS: In a hospital setting, the likelihood of comorbidity with a nonmalarial disease is inversely correlated with increasing blood levels of malaria parasites. Hence, parasite densities provide important information as an indicator for the probability of coinfection, in particular to guide antimicrobial medication.",2018 Jun 15,"['Hogan, Benedikt', 'Eibach, Daniel', 'Krumkamp, Ralf', 'Sarpong, Nimako', 'Dekker, Denise', 'Kreuels, Benno', 'Maiga-Ascofaré, Oumou', 'Gyau Boahen, Kennedy', 'Wiafe Akenten, Charity', 'Adu-Sarkodie, Yaw', 'Owusu-Dabo, Ellis', 'May, Jürgen', None]",Clin Infect Dis,,,False
bdb055fe1931f1117bc4cf30218e66a78e370044,PMC,Immune complex glomerulonephritis of suspected iatrogenic origin in five Japanese Black calves,http://dx.doi.org/10.1292/jvms.17-0544,PMC5989030,29628480,CC BY-NC-ND,"Five Japanese Black embryo transfer calves from a single embryo flush, 30 to 45-days-old, including 4 live animals for clinical examination and 1 dead for necropsy, were presented with a history of decreased milk intake and hypoproteinemia. Consistent clinicopathological abnormalities in the 4 calves presented for clinical evaluation included hyperkalemia, hyperphosphatemia, hypoproteinemia, hypoalbuminemia, hyperbilirubinemia, increased creatine phosphokinase activity, and proteinuria. Four calves ultimately were necropsied and all had histologic evidence of immune complex glomerulonephritis. Glomerulonephritis in these calves was hypothesized to have resulted from the interaction of passively acquired antibodies at birth and active immunization at 7 and 28 days of age with a Salmonella Typhimurium core antigen vaccine.",2018 May 6,"['BERNIER GOSSELIN, Véronique', 'KIM, Dae Y.', 'NAGY, Dusty W.', 'SHOEMAKE, Brian M.', 'SHAW, Daniel P.', 'ROYAL, Angela B.', 'EVANS, Tim J.', 'MIDDLETON, John R.']",J Vet Med Sci,,,True
c7ca65cf313cfa6938c6cf49e6bd4b4dfc6c95f7,PMC,Fluorogen-activating proteins: beyond classical fluorescent proteins,http://dx.doi.org/10.1016/j.apsb.2018.02.001,PMC5989828,29881673,CC BY-NC-ND,"Fluorescence imaging is a powerful technique for the real-time noninvasive monitoring of protein dynamics. Recently, fluorogen activating proteins (FAPs)/fluorogen probes for protein imaging were developed. Unlike the traditional fluorescent proteins (FPs), FAPs do not fluoresce unless bound to their specific small-molecule fluorogens. When using FAPs/fluorogen probes, a washing step is not required for the removal of free probes from the cells, thus allowing rapid and specific detection of proteins in living cells with high signal-to-noise ratio. Furthermore, with different fluorogens, living cell multi-color proteins labeling system was developed. In this review, we describe about the discovery of FAPs, the design strategy of FAP fluorogens, the application of the FAP technology and the advances of FAP technology in protein labeling systems.",2018 May 24,"['Xu, Shengnan', 'Hu, Hai-Yu']",Acta Pharm Sin B,,,False
792b2b2b74f58b9a32b31b57c7930dbfea9895c5,PMC,Correlation between Pneumonia Severity and Pulmonary Complications in Middle East Respiratory Syndrome,http://dx.doi.org/10.3346/jkms.2018.33.e169,PMC5990444,29892209,CC BY-NC,"This nationwide, prospective cohort study evaluated pulmonary function and radiological sequelae according to infection severity in 73 survivors from the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea. Patients with severe pneumonia in MERS-coronavirus infection had more impaired pulmonary function than those with no or mild pneumonia at the 1-year follow-up, which was compatible with the radiological sequelae. Severe pneumonia significantly impairs pulmonary function and makes long radiological sequelae in MERS.",2018 May 10,"['Park, Wan Beom', 'Jun, Kang Il', 'Kim, Gayeon', 'Choi, Jae-Phil', 'Rhee, Ji-Young', 'Cheon, Shinhyea', 'Lee, Chang Hyun', 'Park, Jun-Sun', 'Kim, Yeonjae', 'Joh, Joon-Sung', 'Chin, Bum Sik', 'Choe, Pyeong Gyun', 'Bang, Ji Hwan', 'Park, Sang-Won', 'Kim, Nam Joong', 'Lim, Dong-Gyun', 'Kim, Yeon-Sook', 'Oh, Myoung-don', 'Shin, Hyoung-Shik']",J Korean Med Sci,,,True
72903336c1c94d9acc0491f7aadc93d7365a6934,PMC,Differences among Ophthalmology Patients Referred to Tertiary Medical Centers according to Referral Hospital,http://dx.doi.org/10.3341/kjo.2017.0090,PMC5990643,29770642,CC BY-NC,"PURPOSE: This study aimed to investigate the diagnosis and severity of patients who were referred to tertiary medical centers according to the type and function of the referral hospitals. METHODS: First-visit patients referred from July 2015 to June 2016 were retrospectively reviewed with regard to referral hospital, final diagnosis, treatment necessity, and medical fees for the six months after their first hospital visit. Based on these data, differences in type and function of medical institution were examined. RESULTS: In a comparison of hospitals according to their number of beds, clinics, hospitals and, tertiary hospitals had no differences in the ratio of patients who needed treatment (p = 0.075) and their medical fees over six months (p = 0.372). When hospitals were classified by functional capability in terms of doctors' medical specialty, increasing ratios of patients requiring medical treatment (p < 0.001) and medical fees for six months (p < 0.001) were found in the order of non-eye specialists, eye specialists, and eye specialists in trainee hospital. CONCLUSIONS: Efficient healthcare delivery systems should classify medical institutions by functionality capability based on medical specialties rather than hospital size according to the number of beds.",2018 Jun 4,"['Kim, Heesuk', 'Kim, Hong Kyu', 'Rim, Tyler Hyungtaek', 'Kim, Ji Won', 'Kim, Jin Hyung', 'Kim, Sung Soo']",Korean J Ophthalmol,,,True
a0432d20b18db0900a9074dc773e27bd4b8ad1b8,PMC,Differential network as an indicator of osteoporosis with network entropy,http://dx.doi.org/10.3892/etm.2018.6169,PMC5995033,29896257,CC BY-NC-ND,"Osteoporosis is a common skeletal disorder characterized by a decrease in bone mass and density. The peak bone mass (PBM) is a significant determinant of osteoporosis. To gain insights into the indicating effect of PBM to osteoporosis, this study focused on characterizing the PBM networks and identifying key genes. One biological data set with 12 monocyte low PBM samples and 11 high PBM samples was derived to construct protein-protein interaction networks (PPINs). Based on clique-merging, module-identification algorithm was used to identify modules from PPINs. The systematic calculation and comparison were performed to test whether the network entropy can discriminate the low PBM network from high PBM network. We constructed 32 destination networks with 66 modules divided from monocyte low and high PBM networks. Among them, network 11 was the only significantly differential one (P<0.05) with 8 nodes and 28 edges. All genes belonged to precursors of osteoclasts, which were related to calcium transport as well as blood monocytes. In conclusion, based on the entropy in PBM PPINs, the differential network appears to be a novel therapeutic indicator for osteoporosis during the bone monocyte progression; these findings are helpful in disclosing the pathogenetic mechanisms of osteoporosis.",2018 Jul 16,"['Ma, Lili', 'Du, Hongmei', 'Chen, Guangdong']",Exp Ther Med,,,True
f6e907e13f516564479fe71e2904d14cad572f15,PMC,Viral Fitness Correlates with the Magnitude and Direction of the Perturbation Induced in the Host’s Transcriptome: The Tobacco Etch Potyvirus—Tobacco Case Study,http://dx.doi.org/10.1093/molbev/msy038,PMC5995217,29562354,CC BY-NC,"Determining the fitness of viral genotypes has become a standard practice in virology as it is essential to evaluate their evolutionary potential. Darwinian fitness, defined as the advantage of a given genotype with respect to a reference one, is a complex property that captures, in a single figure, differences in performance at every stage of viral infection. To what extent does viral fitness result from specific molecular interactions with host factors and regulatory networks during infection? Can we identify host genes in functional classes whose expression depends on viral fitness? Here, we compared the transcriptomes of tobacco plants infected with seven genotypes of tobacco etch potyvirus that differ in fitness. We found that the larger the fitness differences among genotypes, the more dissimilar the transcriptomic profiles are. Consistently, two different mutations, one in the viral RNA polymerase and another in the viral suppressor of RNA silencing, resulted in significantly similar gene expression profiles. Moreover, we identified host genes whose expression showed a significant correlation, positive or negative, with the virus' fitness. Differentially expressed genes which were positively correlated with viral fitness activate hormone- and RNA silencing-mediated pathways of plant defense. In contrast, those that were negatively correlated with fitness affect metabolism, reducing growth, and development. Overall, these results reveal the high information content of viral fitness and suggest its potential use to predict differences in genomic profiles of infected hosts.",2018 Jul 19,"['Cervera, Héctor', 'Ambrós, Silvia', 'Bernet, Guillermo P', 'Rodrigo, Guillermo', 'Elena, Santiago F']",Mol Biol Evol,,,True
4ec7c4ec545371f4b8c4a40db7d28fc534674c39,PMC,"Knowledge, Perceptions, and Self-reported Performance of Hand Hygiene Among Registered Nurses at Community-based Hospitals in the Republic of Korea: A Cross-sectional Multi-center Study",http://dx.doi.org/10.3961/jpmph.17.188,PMC5996191,29886707,CC BY-NC,"OBJECTIVES: To assess the nurses’ hand hygiene (HH) knowledge, perception, attitude, and self-reported performance in small- and medium-sized hospitals after Middle East Respiratory Syndrome outbreak. METHODS: The structured questionnaire was adapted from the World Health Organization’s survey. Data were collected between June 26 and July 14, 2017. RESULTS: Nurses showed scores on knowledge (17.6±2.5), perception (69.3±0.8), self-reported HH performance of non-self (86.0±11.0), self-reported performance of self (88.2±11.0), and attitude (50.5±5.5). HH performance rate of non-self was Y(1)=36.678+ 0.555X1 (HH performance rate of self) (adjusted R(2)=0.280, p<0.001). The regression model for performance was Y(4)=18.302+0.247X(41) (peception)+0.232X(42) (attitude)+0.875X(42) (role model); coefficients were significant statistically except attitude, and this model significant statistically (adjusted R(2)=0.191, p<0.001). CONCLUSIONS: Advanced HH education program would be developed and operated continuously. Perception, attitude, role model was found to be a significant predictors of HH performance of self. So these findings could be used in future HH promotion strategies for nurses.",2018 May 14,"Oh, Hyang Soon",J Prev Med Public Health,,,True
d4c836458692801c907aaca8ec7fc1c52b41df43,PMC,Effect of effort‐reward imbalance and burnout on infection control among Ecuadorian nurses,http://dx.doi.org/10.1111/inr.12409,PMC6001576,29114886,CC BY-NC-ND,"BACKGROUND: Nurses are frequently exposed to transmissible infections, yet adherence to infection control measures is suboptimal. There has been inadequate research into how the psychosocial work environment affects compliance with infection control measures, especially in low‐ and middle‐income countries. AIM: To examine the association between effort‐reward imbalance, burnout and adherence to infection control measures among nurses in Ecuador. INTRODUCTION: A cross‐sectional study linking psychosocial work environment indicators to infection control adherence. METHODS: The study was conducted among 333 nurses in four Ecuadorian hospitals. Self‐administered questionnaires assessed demographic variables, perceived infection risk, effort‐reward imbalance, burnout and infection control adherence. RESULTS: Increased effort‐reward imbalance was found to be a unique incremental predictor of exposure to burnout, and burnout was a negative unique incremental predictor of nurses' self‐reported adherence with infection control measures. DISCUSSION: Results suggest an effort‐reward imbalance‐burnout continuum, which, at higher levels, contributes to reduce adherence to infection control. The Ecuadorean government has made large efforts to improve universal access to health care, yet this study suggests that workplace demands on nurses remain problematic. CONCLUSION: This study highlights the contribution of effort‐reward‐imbalance‐burnout continuum to the chain of infection by decreased adherence to infection control of nurses. IMPLICATIONS FOR NURSING POLICY: Health authorities should closely monitor the effect of new policies on psychosocial work environment, especially when expanding services and increasing public accessibility with limited resources. Additionally, organizational and psychosocial interventions targeting effort‐reward imbalance and burnout in nurses should be considered part of a complete infection prevention and control strategy. Further study is warranted to identify interventions that best ameliorate effort‐reward imbalance and burnout in low‐ and middle‐income settings.",2018 Jun 7,"['Colindres, C.V.', 'Bryce, E.', 'Coral‐Rosero, P.', 'Ramos‐Soto, R.M.', 'Bonilla, F.', 'Yassi, A.']",Int Nurs Rev,,,True
53a30619d10014c77807b76f0c19dd270237858d,PMC,Spatio-temporal spread of infectious pathogens of humans,http://dx.doi.org/10.1016/j.idm.2017.05.001,PMC6001966,29928738,CC BY-NC-ND,Spatio-temporal aspects in the propagation of infectious pathogens of humans are reviewed. Mathematical modelling of these issues using metapopulation models is presented.,2017 May 17,"Arino, Julien",Infect Dis Model,,,False
15a02350efb8a42f62b4408ef471986d3cb4a5cd,PMC,A primer on stable parameter estimation and forecasting in epidemiology by a problem-oriented regularized least squares algorithm,http://dx.doi.org/10.1016/j.idm.2017.05.004,PMC6002070,29928741,CC BY-NC-ND,"Public health officials are increasingly recognizing the need to develop disease-forecasting systems to respond to epidemic and pandemic outbreaks. For instance, simple epidemic models relying on a small number of parameters can play an important role in characterizing epidemic growth and generating short-term epidemic forecasts. In the absence of reliable information about transmission mechanisms of emerging infectious diseases, phenomenological models are useful to characterize epidemic growth patterns without the need to explicitly model transmission mechanisms and the natural history of the disease. In this article, our goal is to discuss and illustrate the role of regularization methods for estimating parameters and generating disease forecasts using the generalized Richards model in the context of the 2014–15 Ebola epidemic in West Africa.",2017 May 25,"['Smirnova, Alexandra', 'Chowell, Gerardo']",Infect Dis Model,,,False
2f99e492dc55e196f3a6629961ad2c13062449ac,PMC,Organelles in metabolism and stress responses,http://dx.doi.org/10.1091/mbc.E17-11-0679,PMC6003223,29535175,CC BY-NC-SA,,2018 Mar 15,"['Ferguson, Shawn M.', 'Henne, W. Mike']",Mol Biol Cell,,,False
b3c7cd5491836d0e345797bad2673c79ceaffe67,PMC,Probiotics and Paraprobiotics in Viral Infection: Clinical Application and Effects on the Innate and Acquired Immune Systems,http://dx.doi.org/10.2174/1381612824666180116163411,PMC6006794,29345577,CC BY-NC,"Recently, the risk of viral infection has dramatically increased owing to changes in human ecology such as global warming and an increased geographical movement of people and goods. Howev-er, the efficacy of vaccines and remedies for infectious diseases is limited by the high mutation rates of viruses, especially, RNA viruses. Here, we comprehensively review the effectiveness of several probiot-ics and paraprobiotics (sterilized probiotics) for the prevention or treatment of virally-induced infectious diseases. We discuss the unique roles of these agents in modulating the cross-talk between commensal bacteria and the mucosal immune system. In addition, we provide an overview of the unique mechanism by which viruses are eliminated through the stimulation of type 1 interferon production by probiotics and paraprobiotics via the activation of dendritic cells. Although further detailed research is necessary in the future, probiotics and/or paraprobiotics are expected to be among the rational adjunctive options for the treatment of various viral diseases.",2018 Feb,"['Kanauchi, Osamu', 'Andoh, Akira', 'AbuBakar, Sazaly', 'Yamamoto, Naoki']",Curr Pharm Des,,,True
92ca79afc9f624d2ff6417edfd83e081fcace484,PMC,Performance of TEM-PCR vs Culture for Bacterial Identification in Pediatric Musculoskeletal Infections,http://dx.doi.org/10.1093/ofid/ofy119,PMC6007387,29977969,CC BY-NC-ND,"Improved diagnostics are needed for children with musculoskeletal infections (MSKIs). We assessed the performance of target-enriched multiplex polymerase chain reaction (TEM-PCR) in children with MSKI. TEM-PCR was concordant with culture in pathogen identification and antibiotic susceptibility testing, while increasing the overall yield of pathogen detection. This technology has the potential to inform judicious antimicrobial use early in the disease course.",2018 May 22,"['Wood, James B', 'Sesler, Cheryl', 'Stalons, Donald', 'Grigorenko, Elena', 'Schoenecker, Jonathan G', 'Creech, C Buddy', 'Thomsen, Isaac P']",Open Forum Infect Dis,,,True
a10019330d4147f613949ce0d30e0b0bc66499ea,PMC,Positive-sense RNA viruses reveal the complexity and dynamics of the cellular and viral epitranscriptomes during infection,http://dx.doi.org/10.1093/nar/gky029,PMC6009648,29373715,CC BY-NC,"More than 140 post-transcriptional modifications (PTMs) are known to decorate cellular RNAs, but their incidence, identity and significance in viral RNA are still largely unknown. We have developed an agnostic analytical approach to comprehensively survey PTMs on viral and cellular RNAs. Specifically, we used mass spectrometry to analyze PTMs on total RNA isolated from cells infected with Zika virus, Dengue virus, hepatitis C virus (HCV), poliovirus and human immunodeficiency virus type 1. All five RNA viruses significantly altered global PTM landscapes. Examination of PTM profiles of individual viral genomes isolated by affinity capture revealed a plethora of PTMs on viral RNAs, which far exceeds the handful of well-characterized modifications. Direct comparison of viral epitranscriptomes identified common and virus-specific PTMs. In particular, specific dimethylcytosine modifications were only present in total RNA from virus-infected cells, and in intracellular HCV RNA, and viral RNA from Zika and HCV virions. Moreover, dimethylcytosine abundance during viral infection was modulated by the cellular DEAD-box RNA helicase DDX6. By opening the Pandora’s box on viral PTMs, this report presents numerous questions and hypotheses on PTM function and strongly supports PTMs as a new tier of regulation by which RNA viruses subvert the host and evade cellular surveillance systems.",2018 Jun 20,"['McIntyre, Will', 'Netzband, Rachel', 'Bonenfant, Gaston', 'Biegel, Jason M', 'Miller, Clare', 'Fuchs, Gabriele', 'Henderson, Eric', 'Arra, Manoj', 'Canki, Mario', 'Fabris, Daniele', 'Pager, Cara T']",Nucleic Acids Res,,,True
a12e77068a7406f976f6d13463697b3ed5004c2a,PMC,Positive-sense RNA viruses reveal the complexity and dynamics of the cellular and viral epitranscriptomes during infection,http://dx.doi.org/10.1093/nar/gky029,PMC6009648,29373715,CC BY-NC,"More than 140 post-transcriptional modifications (PTMs) are known to decorate cellular RNAs, but their incidence, identity and significance in viral RNA are still largely unknown. We have developed an agnostic analytical approach to comprehensively survey PTMs on viral and cellular RNAs. Specifically, we used mass spectrometry to analyze PTMs on total RNA isolated from cells infected with Zika virus, Dengue virus, hepatitis C virus (HCV), poliovirus and human immunodeficiency virus type 1. All five RNA viruses significantly altered global PTM landscapes. Examination of PTM profiles of individual viral genomes isolated by affinity capture revealed a plethora of PTMs on viral RNAs, which far exceeds the handful of well-characterized modifications. Direct comparison of viral epitranscriptomes identified common and virus-specific PTMs. In particular, specific dimethylcytosine modifications were only present in total RNA from virus-infected cells, and in intracellular HCV RNA, and viral RNA from Zika and HCV virions. Moreover, dimethylcytosine abundance during viral infection was modulated by the cellular DEAD-box RNA helicase DDX6. By opening the Pandora’s box on viral PTMs, this report presents numerous questions and hypotheses on PTM function and strongly supports PTMs as a new tier of regulation by which RNA viruses subvert the host and evade cellular surveillance systems.",2018 Jun 20,"['McIntyre, Will', 'Netzband, Rachel', 'Bonenfant, Gaston', 'Biegel, Jason M', 'Miller, Clare', 'Fuchs, Gabriele', 'Henderson, Eric', 'Arra, Manoj', 'Canki, Mario', 'Fabris, Daniele', 'Pager, Cara T']",Nucleic Acids Res,,,False
61112e6252f461836d68ffdfba97c244e5b70569,PMC,A case of acute disseminated encephalomyelitis following Mycoplasma pneumoniae infection,http://dx.doi.org/10.1016/j.idcr.2018.03.003,PMC6011136,29942745,CC BY-NC-ND,"We report a case of acute disseminated encephalomyelitis (ADEM) secondary to Mycoplasma pneumoniae infection that failed to improve with methylprednisolone and intravenous immunoglobulin (IVIG); who responded with plasmapheresis. A 21- year- old female with an unremarkable medical history, initially presented to an outside hospital with fever and an influenza-like illness and was subsequently intubated for worsening sensorium. Brain magnetic resonance imaging was suggestive of ADEM or vasculitis for which she received five days of pulse steroids and IVIG. She showed no signs of improvement and was transferred to our hospital for plasmapheresis. Her work up revealed an elevated IgM antibody and positive sputum for Mycoplasma pneumonia by polymerase chain reaction, suggesting the pathogen as the culprit for her ADEM. Intravenous azithromycin and daily plasmapheresis were initiated for seven consecutive days. Following commencement of her treatment, the patient experienced good recovery and was subsequently extubated. She continued to improve with physical therapy and gained mobility, with the help of a walker. Patients commonly present with ADEM following viral infection or vaccination and less frequently post bacterial infection. The current treatment of ADEM due to Mycoplasma pneumoniae is based on limited case reports. Our patient poorly responded to pulse steroids and IVIG, while she markedly improved on azithromycin and plasmapheresis. In patients presenting with encephalopathic signs and neurological manifestations following pneumonia; Mycoplasma pneumoniae infection and subsequent immune-mediated demyelination should be considered.",2018 Mar 12,"['Laila, Alla', 'El-Lababidi, Rania M.', 'Hisham, Mohamed', 'Mooty, Mohammad']",IDCases,,,False
5cf53c279192e23b92dd29e74cf9bdbb3b598244,PMC,"Assessment of transport stress on cattle travelling a long distance (≈648 km), from Jessore (Indian border) to Chittagong, Bangladesh",http://dx.doi.org/10.1136/vetreco-2017-000248,PMC6018847,29955367,CC BY-NC,"The effect of long-distance transport on cattle health has not frequently been studied in Bangladesh. The current study investigated the health conditions, and the extent and pattern of cattle injuries, along with haemato-biochemical and hormonal changes, before and after long-distance transportation (≈648 km) from the market of origin to the market of destination. A total of 100 adult cattle were selected at the Benapole live cattle market, Bangladesh, for physical examination before and after transportation. Fifty of these cattle were randomly selected for additional haemato-biochemical evaluation just before the start of transportation (0 hour), immediately after arrival at the destination market (13.8±0.9 hours after the start of transportation) and 24 hours after arrival at the destination market. The external health conditions and injuries were assessed. Animals were fasting in the vehicle during transportation and provided only with paddy straw and water before sale at the destination market. Before and after transportation, the overall frequency of cattle injuries varied significantly (26 per cent before v 47 per cent after transportation; P<0.001). Cattle health conditions diverged significantly (such as nasal discharge: 15 per cent v 28 per cent; P=0.03). The values of haemoglobin (P=0.01), total erythrocyte count (P=0.001), total leucocyte count (P<0.001), lymphocyte (P=0.005), neutrophil (P=0.01) and eosinophil (P=0.01) varied significantly. The values of serum total protein (P=0.006), creatine kinase (P<0.001), triglyceride (P=0.04), calcium (P=0.003), phosphorus (P<0.001) and alkaline phosphatase (P=0.04) significantly differed. The overall findings indicate a high degree of transport stress and poor animal welfare.",2018 Jun 26,"['Alam, Mahabub', 'Hasanuzzaman, Md', 'Hassan, Mohammad Mahmudul', 'Rakib, Tofazzal Md', 'Hossain, Md Emran', 'Rashid, Md Harun', 'Sayeed, Md Abu', 'Philips, Lindsay B', 'Hoque, Md Ahasanul']",Vet Rec Open,,,True
d0464b088c3c7a939a2f1862f7e910ffd9340eeb,PMC,Clinical and laboratory profiles of hospitalized children with acute respiratory virus infection,http://dx.doi.org/10.3345/kjp.2018.61.6.180,PMC6021362,29963101,CC BY-NC,"PURPOSE: Despite the availability of molecular methods, identification of the causative virus in children with acute respiratory infections (ARIs) has proven difficult as the same viruses are often detected in asymptomatic children. METHODS: Multiplex reverse transcription polymerase chain reaction assays were performed to detect 15 common respiratory viruses in children under 15 years of age who were hospitalized with ARI between January 2013 and December 2015. Viral epidemiology and clinical profiles of single virus infections were evaluated. RESULTS: Of 3,505 patients, viruses were identified in 2,424 (69.1%), with the assay revealing a single virus in 1,747 cases (49.8%). While major pathogens in single virus-positive cases differed according to age, human rhinovirus (hRV) was common in patients of all ages. Respiratory syncytial virus (RSV), influenza virus (IF), and human metapneumovirus (hMPV) were found to be seasonal pathogens, appearing from fall through winter and spring, whereas hRV and adenovirus (AdV) were detected in every season. Patients with ARIs caused by RSV and hRV were frequently afebrile and more commonly had wheezing compared with patients with other viral ARIs. Neutrophil-dominant inflammation was observed in ARIs caused by IF, AdV, and hRV, whereas lymphocyte-dominant inflammation was observed with RSV A, parainfluenza virus, and hMPV. Monocytosis was common with RSV and AdV, whereas eosinophilia was observed with hRV. CONCLUSION: In combination with viral identification, recognition of virus-specific clinical and laboratory patterns will expand our understanding of the epidemiology of viral ARIs and help us to establish more efficient therapeutic and preventive strategies.",2018 Jun 25,"['Choi, Eunjin', 'Ha, Kee-Soo', 'Song, Dae Jin', 'Lee, Jung Hwa', 'Lee, Kwang Chul']",Korean J Pediatr,,,True
53cf48ec1726de4e093378e48a74632bf485cca6,PMC,Molecular surveillance of canine distemper virus in diarrhoetic puppies in northeast China from May 2014 to April 2015,http://dx.doi.org/10.1292/jvms.17-0559,PMC6021885,29695673,CC BY-NC-ND,"To trace the prevalence of canine distemper virus (CDV) in diarrhoetic dogs, a total of 201 stool samples were collected in the Heilongjiang province of northeastern China from May 2014 to April 2015. The 201 fecal samples were subjected to the detection of CDV by using RT-PCR targeting the partial N gene, phylogenetic analysis based on the complete H gene, and co-infection analysis. Results indicated that 24.88% (50/201) of the samples were positive for CDV. The fifty CDV samples exhibited an overall co-infection rate of 94% (47/50) with four enteric viruses (82%, 41/50) and five bacteria (72%, 36/50). The positivity rate of CDV exhibited differences among regions, seasons, ages and immunization status. Phylogenetic analysis of the complete H genes (n=6) revealed that the CDV strains identified in our study belonged to the Asia-1 group, and showed genetic diversities. These data provide evidence that there are a number of genetically diverse CDV Asia-1 strains circulating in diarrhoetic dogs in northeastern China; the CDV-affected animals exhibit the high co-infection with other enteric viruses and bacteria.",2018 Jun 24,"['LI, Chunqiu', 'GUO, Donghua', 'WU, Rui', 'KONG, Fanzhi', 'ZHAI, Junjun', 'YUAN, Dongwei', 'SUN, Dongbo']",J Vet Med Sci,,,True
e2a54d852edc4fc5b2e136f5840a5b07631bdae9,PMC,Molecular surveillance of canine distemper virus in diarrhoetic puppies in northeast China from May 2014 to April 2015,http://dx.doi.org/10.1292/jvms.17-0559,PMC6021885,29695673,CC BY-NC-ND,"To trace the prevalence of canine distemper virus (CDV) in diarrhoetic dogs, a total of 201 stool samples were collected in the Heilongjiang province of northeastern China from May 2014 to April 2015. The 201 fecal samples were subjected to the detection of CDV by using RT-PCR targeting the partial N gene, phylogenetic analysis based on the complete H gene, and co-infection analysis. Results indicated that 24.88% (50/201) of the samples were positive for CDV. The fifty CDV samples exhibited an overall co-infection rate of 94% (47/50) with four enteric viruses (82%, 41/50) and five bacteria (72%, 36/50). The positivity rate of CDV exhibited differences among regions, seasons, ages and immunization status. Phylogenetic analysis of the complete H genes (n=6) revealed that the CDV strains identified in our study belonged to the Asia-1 group, and showed genetic diversities. These data provide evidence that there are a number of genetically diverse CDV Asia-1 strains circulating in diarrhoetic dogs in northeastern China; the CDV-affected animals exhibit the high co-infection with other enteric viruses and bacteria.",2018 Jun 24,"['LI, Chunqiu', 'GUO, Donghua', 'WU, Rui', 'KONG, Fanzhi', 'ZHAI, Junjun', 'YUAN, Dongwei', 'SUN, Dongbo']",J Vet Med Sci,,,False
b1ce65cde86a570d32ed8ed5462bbff9c6a33fbb,PMC,Novel Method of 3-Dimensional Graphical Representation for Proteins and Its Application,http://dx.doi.org/10.1177/1176934318777755,PMC6024350,29977111,CC BY-NC,"In this article, we propose a 3-dimensional graphical representation of protein sequences based on 10 physicochemical properties of 20 amino acids and the BLOSUM62 matrix. It contains evolutionary information and provides intuitive visualization. To further analyze the similarity of proteins, we extract a specific vector from the graphical representation curve. The vector is used to calculate the similarity distance between 2 protein sequences. To prove the effectiveness of our approach, we apply it to 3 real data sets. The results are consistent with the known evolution fact and show that our method is effective in phylogenetic analysis.",2018 Jun 12,"['Qi, Zhao-Hui', 'Li, Ke-Cheng', 'Ma, Jin-Long', 'Yao, Yu-Hua', 'Liu, Ling-Yun']",Evol Bioinform Online,,,True
7c9b0de06457ee197e904b3bc7f312ccb888baa7,PMC,N-terminal Domain of the Spike Protein of Porcine Epidemic Diarrhea Virus as a New Candidate Molecule for a Mucosal Vaccine,http://dx.doi.org/10.4110/in.2018.18.e21,PMC6026690,29984039,CC BY-NC,"Porcine epidemic diarrhea virus (PEDV) is a contagious coronavirus infecting pigs that leads to significant economic losses in the swine industry. Given that PEDV infection occurs in gut epithelial cells mainly via the fecal-oral route, induction of PEDV-specific immune responses in the mucosal compartment is required for protective immunity against viral infection. However, an effective mucosal vaccine against the currently prevalent PEDV strain is not available. In this study, we demonstrated that the N-terminal domain (NTD) of the spike (S) protein of PEDV represents a new vaccine candidate molecule to be applied via the mucosal route. We first established an Escherichia coli expression system producing the partial NTD (NTD(231–501)) of the PEDV S protein. Orally administered NTD(231–501) protein specifically interacted with the apical area of M cells in the follicle-associated epithelium of Peyer's patch. Additionally, the NTD protein induced antigen-specific immune responses in both the systemic and mucosal immune compartments when administered orally. Collectively, we propose the NTD of the PEDV S protein to be a candidate mucosal vaccine molecule.",2018 Jun 15,"['Kim, Sae-Hae', 'Cho, Byeol-Hee', 'Lee, Kyung-Yeol', 'Jang, Yong-Suk']",Immune Netw,,,True
1694b4f8e456f966ff1fe215161bae59e59148df,PMC,A vaccine effective against Zika virus is theoretically possible but may not be delivered anytime soon,http://dx.doi.org/10.2147/RRTM.S108992,PMC6028058,30050335,CC BY-NC,"Following the first report in May 2015 of the unexpected emergence of Zika in north east Brazil, there has been an explosive epidemic of this infection across Latin America. The outbreak has caused alarm among social and news media as to the virulence and transmission potential of the Aedes mosquito-borne virus. This debate is heightened by the proximity, both in time and distance, to the forthcoming Olympic Games to be held in Rio de Janeiro this August, provoking fears for the safety of athletes and spectators alike. The threat, real or perceived, is exacerbated by the movement between nations in the same or separate continents of persons who act unwittingly as asymptomatic carriers. Pregnant females are considered at greatest risk because microcephaly in newborn infants is linked to, if not yet proven as caused by, Zika infection. In February this year, the World Health Organization declared that further to the then unconfirmed association between the virus and the clinical manifestations of microcephaly and also Guillain-Barré syndrome, the Zika epidemic was a “public health emergency of international concern”. No anti-Zika therapy, vaccine or drug, is currently available and while the production of the former has now been prioritized by multiple funding agencies, the history of infectious disease vaccine development indicates that this may take several years to reach the market place. The fact that Zika is a close relative of yellow fever and Japanese encephalitis viruses, for both of which there are already effective vaccines, provides a rational basis for the fast-tracked laboratory-based preparation of a candidate vaccine. However, undertaking clinical trials on pregnant females provides ethical and practical hurdles to overcome before licensure is granted for public administration. Meanwhile, public health management strategies, including mosquito control programs to reduce breeding, are needed to limit the global spread of this re-emerging disease.",2016 Jul 5,"Taylor-Robinson, Andrew W",Res Rep Trop Med,,,True
bfc521f036ead8d21f832497328d5be3e7852a66,PMC,Drawing on disorder: How viruses use histone mimicry to their advantage,http://dx.doi.org/10.1084/jem.20180099,PMC6028506,29934321,CC BY-NC-SA,"Humans carry trillions of viruses that thrive because of their ability to exploit the host. In this exploitation, viruses promote their own replication by suppressing the host antiviral response and by inducing changes in host biosynthetic processes, often with extremely small genomes of their own. In the review, we discuss the phenomenon of histone mimicry by viral proteins and how this mimicry allows the virus to dial in to the cell’s transcriptional processes and establish a cell state that promotes infection. We suggest that histone mimicry is part of a broader viral strategy to use intrinsic protein disorder as a means to overcome the size limitations of its own genome and to maximize its impact on host protein networks. In particular, we discuss how intrinsic protein disorder may enable viral proteins to interfere with phase-separated host protein condensates, including those that contribute to chromatin-mediated control of gene expression.",2018 Jul 2,"['Tarakhovsky, Alexander', 'Prinjha, Rab K.']",J Exp Med,,,True
7248a954a71c38b84dcc81be1105e231728286fc,PMC,Predicting Mortality in Patients with Tuberculous Destroyed Lung Receiving Mechanical Ventilation,http://dx.doi.org/10.4046/trd.2017.0126,PMC6030661,29926549,CC BY-NC,"BACKGROUND: Patients with acute respiratory failure secondary to tuberculous destroyed lung (TDL) have a poor prognosis. The aim of the present retrospective study was to develop a mortality prediction model for TDL patients who require mechanical ventilation. METHODS: Data from consecutive TDL patients who had received mechanical ventilation at a single university-affiliated tertiary care hospital in Korea were reviewed. Binary logistic regression was used to identify factors predicting intensive care unit (ICU) mortality. A TDL on mechanical Ventilation (TDL-Vent) score was calculated by assigning points to variables according to β coefficient values. RESULTS: Data from 125 patients were reviewed. A total of 36 patients (29%) died during ICU admission. On the basis of multivariate analysis, the following factors were included in the TDL-Vent score: age ≥65 years, vasopressor use, and arterial partial pressure of oxygen/fraction of inspired oxygen ratio <180. In a second regression model, a modified score was then calculated by adding brain natriuretic peptide. For TDL-Vent scores 0 to 3, the 60-day mortality rates were 11%, 27%, 30%, and 77%, respectively (p<0.001). For modified TDL-Vent scores 0 to ≥3, the 60-day mortality rates were 0%, 21%, 33%, and 57%, respectively (p=0.001). For both the TDL-Vent score and the modified TDL-Vent score, the areas under the receiver operating characteristic curve were larger than that of other illness severity scores. CONCLUSION: The TDL-Vent model identifies TDL patients on mechanical ventilation with a high risk of mortality. Prospective validation studies in larger cohorts are now warranted.",2018 Jul 19,"['Kim, Won-Young', 'Kim, Mi-Hyun', 'Jo, Eun-Jung', 'Eom, Jung Seop', 'Mok, Jeongha', 'Kim, Ki Uk', 'Park, Hye-Kyung', 'Lee, Min Ki', 'Lee, Kwangha']",Tuberc Respir Dis (Seoul),,,True
e377ca709f90653eaf5aedc93138e63789faec3f,PMC,Predicting Mortality in Patients with Tuberculous Destroyed Lung Receiving Mechanical Ventilation,http://dx.doi.org/10.4046/trd.2017.0126,PMC6030661,29926549,CC BY-NC,"BACKGROUND: Patients with acute respiratory failure secondary to tuberculous destroyed lung (TDL) have a poor prognosis. The aim of the present retrospective study was to develop a mortality prediction model for TDL patients who require mechanical ventilation. METHODS: Data from consecutive TDL patients who had received mechanical ventilation at a single university-affiliated tertiary care hospital in Korea were reviewed. Binary logistic regression was used to identify factors predicting intensive care unit (ICU) mortality. A TDL on mechanical Ventilation (TDL-Vent) score was calculated by assigning points to variables according to β coefficient values. RESULTS: Data from 125 patients were reviewed. A total of 36 patients (29%) died during ICU admission. On the basis of multivariate analysis, the following factors were included in the TDL-Vent score: age ≥65 years, vasopressor use, and arterial partial pressure of oxygen/fraction of inspired oxygen ratio <180. In a second regression model, a modified score was then calculated by adding brain natriuretic peptide. For TDL-Vent scores 0 to 3, the 60-day mortality rates were 11%, 27%, 30%, and 77%, respectively (p<0.001). For modified TDL-Vent scores 0 to ≥3, the 60-day mortality rates were 0%, 21%, 33%, and 57%, respectively (p=0.001). For both the TDL-Vent score and the modified TDL-Vent score, the areas under the receiver operating characteristic curve were larger than that of other illness severity scores. CONCLUSION: The TDL-Vent model identifies TDL patients on mechanical ventilation with a high risk of mortality. Prospective validation studies in larger cohorts are now warranted.",2018 Jul 19,"['Kim, Won-Young', 'Kim, Mi-Hyun', 'Jo, Eun-Jung', 'Eom, Jung Seop', 'Mok, Jeongha', 'Kim, Ki Uk', 'Park, Hye-Kyung', 'Lee, Min Ki', 'Lee, Kwangha']",Tuberc Respir Dis (Seoul),,,False
9c71b86e38ae06503c1dc05abea7743ef3e7851e,PMC,Low Lymphocyte Proportion in Bronchoalveolar Lavage Fluid as a Risk Factor Associated with the Change from Trimethoprim/sulfamethoxazole used as First-Line Treatment for Pneumocystis jirovecii Pneumonia,http://dx.doi.org/10.3947/ic.2018.50.2.110,PMC6031595,29968978,CC BY-NC,"BACKGROUND: Trimethoprim/sufamethoxazole (TMP/SMX) is the recommended treatment for Pneumocystis jirovecii pneumonia (PCP). However, the efficacy and the safety of alternative salvage treatments are less guarauteed especially when patient experiences treatment failure and/or an adverse drug reactions (ADR). The purpose of this study is to recognize potential risk factors imitating successful treatment with TMP/SMX among PCP patients. MATERIALS AND METHODS: Ninety one adult patients diagnosed with PCP were included after searching electronical medical records from January 2013 through July 2015 at Asan Medical Center Seoul, Korea. We compared clinical characteristics and laboratory findings including bronchoalveolar lavage (BAL) fluid analysis in patients who experienced TMP/SMX treatment failure or ADR (the case group) versus those who did not (the control group). RESULTS: Among the enrolled PCP patients, 39 (42.9%) required salvage treatment owing to either treatment failure (28, 28.6%) and/or ADR (17, 18.7%). The BAL lymphocyte percentage (25% [IQR, 8–40%] vs. 47% [IQR, 15–62%]; P = 0.005) was lower in the case group. Diabetes mellitus (adjusted odds ratio [aOR] 4.98, 95% confidence interval [95% CI] 1.20–18.58), glomerular filtration rate ≤50 mL/min (aOR 4.48, 95% CI 1.08–18.66), and BAL lymphocyte percentage ≤45% (aOR 9.25, 95% CI 2.47–34.58) were independently associated with the case group in multivariate analysis. CONCLUSION: This study suggests that BAL lymphocyte count may play some role during PCP treatment. Further studies should be followed to reveal what the role of BAL lymphocyte is in the PCP treatment.",2018 Jun 26,"['Kim, Tark', 'Sung, Heungsup', 'Chong, Yong Pil', 'Kim, Sung-Han', 'Choo, Eun Ju', 'Choi, Sang-Ho', 'Kim, Tae Hyong', 'Woo, Jun Hee', 'Kim, Yang Soo', 'Lee, Sang-Oh']",Infect Chemother,,,True
24ec3df6486c04e0eb67d213475f3f1b20fe9fec,PMC,Guideline for Antibiotic Use in Adults with Community-acquired Pneumonia,http://dx.doi.org/10.3947/ic.2018.50.2.160,PMC6031596,29968985,CC BY-NC,"Community-acquired pneumonia is common and important infectious disease in adults. This work represents an update to 2009 treatment guideline for community-acquired pneumonia in Korea. The present clinical practice guideline provides revised recommendations on the appropriate diagnosis, treatment, and prevention of community-acquired pneumonia in adults aged 19 years or older, taking into account the current situation regarding community-acquired pneumonia in Korea. This guideline may help reduce the difference in the level of treatment between medical institutions and medical staff, and enable efficient treatment. It may also reduce antibiotic resistance by preventing antibiotic misuse against acute lower respiratory tract infection in Korea.",2018 Jun 26,"['Lee, Mi Suk', 'Oh, Jee Youn', 'Kang, Cheol-In', 'Kim, Eu Suk', 'Park, Sunghoon', 'Rhee, Chin Kook', 'Jung, Ji Ye', 'Jo, Kyung-Wook', 'Heo, Eun Young', 'Park, Dong-Ah', 'Suh, Gee Young', 'Kiem, Sungmin']",Infect Chemother,,,True
68c6921af95469f234a2405a9234d5c5e9695bb8,PMC,An Imported Case of Brucella melitensis Infection in South Korea,http://dx.doi.org/10.3947/ic.2018.50.2.149,PMC6031603,29968983,CC BY-NC,"Brucellosis is a zoonotic infection that is usually transmitted from cattle to humans through ingestion of animal milk, direct contact with animal parts, or inhalation of aerosolized particles. In Korea, brucellosis seem to be transmitted through close contact with blood, fetus, urine, and placenta of domestic cow that has been infected by Brucella abortus, or inhalation of B. arbortus while examining or slaughtering cow. Brucella melitensis infection is rare in Korea and there have been no reported cases of B. melitensis originating from other countries until now. This report details a case of complicated brucellosis with infective spondylitis in a 48-year-old male construction worker recently returned from Iraq. Infection with B. melitensis was confirmed using 16s rRNA sequencing and omp31 gene analysis. The patient was successfully treated using a combination of rifampin, doxycycline, and streptomycin, in accordance with WHO guidelines. This is the first reported case of complicated brucellosis with infective spondylitis in Korea caused by B. melitensis originating from Iraq.",2018 Jun 14,"['Lee, Jee Young', 'Jeon, Yongduk', 'Ahn, Mi Young', 'Ann, Hea Won', 'Jung, In Young', 'Jung, Wooyong', 'Kim, Moo Hyun', 'Ahn, Jin Young', 'Song, Je Eun', 'Kim, Yong Chan', 'Oh, Dong Hyun', 'Kim, Eun Jin', 'Jeong, Su Jin', 'Ku, Nam Su', 'Kim, Hyunsoo', 'Lee, Kyungwon', 'Kim, June Myung', 'Choi, Jun Yong']",Infect Chemother,,,True
fdb66dfc7edf5a86eb121409bf6db0c0c59eded7,PMC,Cell free preparations of probiotics exerted antibacterial and antibiofilm activities against multidrug resistant E. coli,http://dx.doi.org/10.1016/j.jsps.2018.03.004,PMC6035330,29991904,CC BY-NC-ND,"The sharp increase in antibiotic resistance imposes a global threat to human health and the discovery of effective antimicrobial alternatives is needed. The use of probiotics to combat bacterial pathogens has gained a rising interest. Pathogenic Escherichia coli is causative of multiple clinical syndromes such as diarrheal diseases, meningitis and urinary tract infections. In this work, we evaluated the efficacy of probiotics to control multidrug-resistant E. coli and reduce their ability to form biofilms. Six E. coli resistant to at least five antibiotics (Ceftazidime, Ampicillin, Clarithromycin, Amoxicillin + Clavulanic Acid and Ceftriaxone) were isolated in this work. Preparations of cell-free spent media (CFSM) of six probiotics belonging to the genus Bifidobacterium and Lactobacillus which were grown in Man-Rogosa-Sharpe (MRS) broth exhibited strong antibacterial activity (inhibition zones of 11.77–23.10 mm) against all E. coli isolates. Two E. coli isolates, namely E. coli WW1 and IC2, which were most resistant to all antibiotics were subjected to antibiofilm experiments. Interestingly, the CFSM of MRS fermented by all probiotics resulted in inhibition of biofilm formation while B. longum caused highest inhibition (57.94%) in case of E. coli IC2 biofilms and L. plantarum was responsible for 64.57% reduction of E. coli WW1 biofilms. On the other hand, CFSM of skim milk fermented by L. helveticus and L. rhamnosus exhibited a slight inhibitory activity against IC2 isolate (inhibition percentage of 31.52 and 17. 68, respectively) while WW1 isolate biofilms was reduced by CFSM of milk fermented by B. longum and L. helveticus (70.81 and 69.49 reduction percentage, respectively). These results support the effective use of probiotics as antimicrobial alternatives and to eradicate biofilms formed by multidrug-resistant E. coli.",2018 Jul 12,"['Abdelhamid, Ahmed G.', 'Esaam, Aliaa', 'Hazaa, Mahmoud M.']",Saudi Pharm J,,,False
4a32929dbc801a7e96e900f42f242f93057211ab,PMC,Gene Expression Detection Assay for Cancer Clinical Use,http://dx.doi.org/10.7150/jca.24744,PMC6036716,30026820,CC BY-NC,"Cancer is a genetic disease where genetic variations cause abnormally functioning genes that appear to alter expression. Proteins, the final products of gene expression, determine the phenotypes and biological processes. Therefore, detecting gene expression levels can be used for cancer diagnosis, prognosis, and treatment prediction in a clinical setting. In this review, we investigated six gene expression assay systems (qRT-PCR, DNA microarray, nCounter, RNA-Seq, FISH, and tissue microarray) that are currently being used in clinical cancer studies. Some of these methods are also commonly used in a modified way; for example, detection of DNA content or protein expression. Herein, we discuss their principles, sample preparation, design, quantification and sensitivity, data analysis, time for sample preparation and processing, and cost. We also compared these methods according to their sample selection, particularly for the feasibility of using formalin-fixed paraffin-embedded (FFPE) samples, which are routinely archived for clinical cancer studies. We intend to provide a guideline for choosing an assay method with respect to its oncological applications in a clinical setting.",2018 Jun 5,"['Narrandes, Shavira', 'Xu, Wayne']",J Cancer,,,True
317f324d1116fd3d2d4933450d87528207846e36,PMC,Development of a nasal spray containing xylometazoline hydrochloride and iota-carrageenan for the symptomatic relief of nasal congestion caused by rhinitis and sinusitis,http://dx.doi.org/10.2147/IJGM.S167123,PMC6037157,30013382,CC BY-NC,"INTRODUCTION: Xylometazoline hydrochloride (HCl) is a nasal decongestant that causes vasoconstriction in the nasal submucosa. It has been used for more than 50 years for the treatment of nasal congestion caused by rhinitis/sinusitis. Iota-carrageenan is effective against a broad variety of respiratory viruses, which are the most common cause of infections of the upper respiratory tract. Therefore, it is used as the active component in the antiviral nasal spray Coldamaris prophylactic (1.2 mg/mL iota-carrageenan in 0.5% NaCl) and other medical device nasal sprays that are approved and marketed in the EU. Recently, we developed a nasal spray formulation containing both xylometazoline HCl (0.05%) and iota-carrageenan (0.12%) that provides decongestion and antiviral protection of the nasal mucosa at the same time. RESULTS: A set of in vitro experiments revealed that the vasoconstrictive properties of xylometazoline HCl and the antiviral effectiveness of iota-carrageenan against human rhinovirus (hRV) 1a, hRV8 and human coronavirus OC43 were maintained in the formulation containing these two compounds. Permeation experiments using bovine nasal mucosa showed that iota-carrageenan had no significant influence on the permeation of xylometazoline HCl. Finally, in the local tolerance and toxicity study, it was shown that the formulation was well tolerated at the application site with no occurrence of erythema or edema in the nostrils of all rabbits or any signs of toxicity in any of the organs and tissues inspected. CONCLUSION: Investigations on compatibility of xylometazoline HCl and iota-carrageenan demonstrated that the substances do not influence each other, allowing both to fulfill their known specific clinical efficacy (xylometazoline HCl) and effectiveness (iota-carrageenan).",2018 Jul 4,"['Graf, Christine', 'Bernkop-Schnürch, Andreas', 'Egyed, Alena', 'Koller, Christiane', 'Prieschl-Grassauer, Eva', 'Morokutti-Kurz, Martina']",Int J Gen Med,,,True
560c831e215a39066388a9b94b7a576407d2d3f6,PMC,The intrinsic vulnerability of networks to epidemics,http://dx.doi.org/10.1016/j.ecolmodel.2018.05.013,PMC6039859,30210182,CC BY-NC-ND,"Contact networks are convenient models to investigate epidemics, with nodes and links representing potential hosts and infection pathways, respectively. The outcomes of outbreak simulations on networks are driven both by the underlying epidemic model, and by the networks’ structural properties, so that the same pathogen can generate different epidemic dynamics on different networks. Here we ask whether there are general properties that make a contact network intrinsically vulnerable to epidemics (that is, regardless of specific epidemiological parameters). By conducting simulations on a large set of modelled networks, we show that, when a broad range of network topologies is taken into account, the effect of specific network properties on outbreak magnitude is stronger than that of fundamental pathogen features such as transmission rate, infection duration, and immunization ability. Then, by focusing on a large set of real world networks of the same type (potential contacts between field voles, Microtus agrestis), we showed how network structure can be used to accurately assess the relative, intrinsic vulnerability of networks towards a specific pathogen, even when those have limited topological variability. These results have profound implications for how we prevent disease outbreaks; in many real world situations, the topology of host contact networks can be described and used to infer intrinsic vulnerability. Such an approach can increase preparedness and inform preventive measures against emerging diseases for which limited epidemiological information is available, enabling the identification of priority targets before an epidemic event.",2018 Sep 10,"['Strona, G.', 'Carstens, C.J.', 'Beck, P.S.A.', 'Han, B.A.']",Ecol Modell,,,False
83e5553035f500f4bcc4aeeaa41aa74ebf578567,PMC,A Single-Center Study of Viral Respiratory Tract Infections in Hospitalized Children From the Kurdistan Region of Iraq,http://dx.doi.org/10.1177/2333794X18784996,PMC6042015,30014009,CC BY-NC,"Viral respiratory infections are among the most common causes of disease in humans, particularly in young children, and remain a major public health problem worldwide. For many geographic regions, there is limited epidemiological information on the main causative agents of these diseases. In this article, we investigated, in a prospective study, the viral agents leading to acute respiratory disease in children younger than 15 years of age who were admitted to the pediatric emergency unit of a major teaching hospital in Erbil City, capital of the Kurdistan region, Iraq. Nasopharyngeal samples obtained from 269 hospitalized children were analyzed for viral respiratory pathogens using the xTAG Respiratory Virus Panel Fast assay, and the data were correlated with the clinical and demographic information available for these patients. One or more respiratory virus(es) were detected in 203 out of 269 (75.5%) samples. The most frequent viruses were enterovirus/rhinovirus (n = 88; 32.7%), respiratory syncytial virus (n = 55; 20.4%), and human metapneumovirus (n = 36; 13.4%). In 42 samples (15.6%), coinfections with 2 or more respiratory viruses were detected, with enterovirus/rhinovirus, respiratory syncytial virus, human metapneumovirus, and adenovirus being identified as the most common agents in viral coinfections in these patients.",2018 Jul 10,"['Hassan, Dlshad A.', 'Rachid, Shwan K.', 'Ziebuhr, John']",Glob Pediatr Health,,,True
e1d8c7f82bea0b322ce13645fd051d992a2cec84,PMC,Differentiated human airway organoids to assess infectivity of emerging influenza virus,http://dx.doi.org/10.1073/pnas.1806308115,PMC6042130,29891677,CC BY-NC-ND,"Novel reassortant avian influenza H7N9 virus and pandemic 2009 H1N1 (H1N1pdm) virus cause human infections, while avian H7N2 and swine H1N1 virus mainly infect birds and pigs, respectively. There is no robust in vitro model for assessing the infectivity of emerging viruses in humans. Based on a recently established method, we generated long-term expanding 3D human airway organoids which accommodate four types of airway epithelial cells: ciliated, goblet, club, and basal cells. We report differentiation conditions which increase ciliated cell numbers to a nearly physiological level with synchronously beating cilia readily discernible in every organoid. In addition, the differentiation conditions induce elevated levels of serine proteases, which are essential for productive infection of human influenza viruses and low-pathogenic avian influenza viruses. We also established improved 2D monolayer culture conditions for the differentiated airway organoids. To demonstrate the ability of differentiated airway organoids to identify human-infective virus, 3D and 2D differentiated airway organoids are applied to evaluate two pairs of viruses with known distinct infectivity in humans, H7N9/Ah versus H7N2 and H1N1pdm versus an H1N1 strain isolated from swine (H1N1sw). The human-infective H7N9/Ah virus replicated more robustly than the poorly human-infective H7N2 virus; the highly human-infective H1N1pdm virus replicated to a higher titer than the counterpart H1N1sw. Collectively, we developed differentiated human airway organoids which can morphologically and functionally simulate human airway epithelium. These differentiated airway organoids can be applied for rapid assessment of the infectivity of emerging respiratory viruses to human.",2018 Jun 26,"['Zhou, Jie', 'Li, Cun', 'Sachs, Norman', 'Chiu, Man Chun', 'Wong, Bosco Ho-Yin', 'Chu, Hin', 'Poon, Vincent Kwok-Man', 'Wang, Dong', 'Zhao, Xiaoyu', 'Wen, Lei', 'Song, Wenjun', 'Yuan, Shuofeng', 'Wong, Kenneth Kak-Yuen', 'Chan, Jasper Fuk-Woo', 'To, Kelvin Kai-Wang', 'Chen, Honglin', 'Clevers, Hans', 'Yuen, Kwok-Yung']",Proc Natl Acad Sci U S A,,,False
793bb8ec176e4a5df8323e0bd2276e134b958b5f,PMC,Differentiated human airway organoids to assess infectivity of emerging influenza virus,http://dx.doi.org/10.1073/pnas.1806308115,PMC6042130,29891677,CC BY-NC-ND,"Novel reassortant avian influenza H7N9 virus and pandemic 2009 H1N1 (H1N1pdm) virus cause human infections, while avian H7N2 and swine H1N1 virus mainly infect birds and pigs, respectively. There is no robust in vitro model for assessing the infectivity of emerging viruses in humans. Based on a recently established method, we generated long-term expanding 3D human airway organoids which accommodate four types of airway epithelial cells: ciliated, goblet, club, and basal cells. We report differentiation conditions which increase ciliated cell numbers to a nearly physiological level with synchronously beating cilia readily discernible in every organoid. In addition, the differentiation conditions induce elevated levels of serine proteases, which are essential for productive infection of human influenza viruses and low-pathogenic avian influenza viruses. We also established improved 2D monolayer culture conditions for the differentiated airway organoids. To demonstrate the ability of differentiated airway organoids to identify human-infective virus, 3D and 2D differentiated airway organoids are applied to evaluate two pairs of viruses with known distinct infectivity in humans, H7N9/Ah versus H7N2 and H1N1pdm versus an H1N1 strain isolated from swine (H1N1sw). The human-infective H7N9/Ah virus replicated more robustly than the poorly human-infective H7N2 virus; the highly human-infective H1N1pdm virus replicated to a higher titer than the counterpart H1N1sw. Collectively, we developed differentiated human airway organoids which can morphologically and functionally simulate human airway epithelium. These differentiated airway organoids can be applied for rapid assessment of the infectivity of emerging respiratory viruses to human.",2018 Jun 26,"['Zhou, Jie', 'Li, Cun', 'Sachs, Norman', 'Chiu, Man Chun', 'Wong, Bosco Ho-Yin', 'Chu, Hin', 'Poon, Vincent Kwok-Man', 'Wang, Dong', 'Zhao, Xiaoyu', 'Wen, Lei', 'Song, Wenjun', 'Yuan, Shuofeng', 'Wong, Kenneth Kak-Yuen', 'Chan, Jasper Fuk-Woo', 'To, Kelvin Kai-Wang', 'Chen, Honglin', 'Clevers, Hans', 'Yuen, Kwok-Yung']",Proc Natl Acad Sci U S A,,,True
cd226106aef486ea318b5426295de4059cc88c10,PMC,"Meeting report: 30th International Conference on Antiviral Research, in Atlanta, GA, USA",http://dx.doi.org/10.1177/2040206618783924,PMC6043914,29954186,CC BY-NC,"The 30th International Conference on Antiviral Research was held in Atlanta, GA, USA, from 21 to 25 May 2017. Each year, the International Society for Antiviral Research (ISAR) presents three major awards, this year to Mike Sofia (Elion award), David Chu (Holý award) and Maaike Everts (Prusoff award). Also this year, the inaugural ISAR Women in Science award lecture was presented by Priscilla Yang. For several years, International Conference on Antiviral Research (ICAR) has included at least one Keynote lecture, this year there were four. Although there are accounts of only these eight lectures, they reflect the diversity that is characteristic of ICAR – employment (academia, industry, public health), type of research (virus biology, potential antiviral targets, antiviral drugs, research organisation) and a range of viruses. For example, the viruses included were hepatitis C virus and hepatitis B virus (Mike Sofia), HIV and hepatitis B virus (David Chu), multiple antiviral projects (Maaike Everts), dengue (Priscilla Yang), rhinovirus C (Ann Palmenberg), polio (Mark Pallansch), HIV (Eric Hunter) and Zika virus (Pei-Yong Shi). This report ends with my personal comments giving examples in which this diversity can bring benefits. The 31st ICAR will be in Porto, Portugal, 11–15 June 2018.",2018 Jun 28,"Vere Hodge, R Anthony",Antivir Chem Chemother,,,True
1c3d3ea935a9625190ebf6f76b035999b03e03f0,PMC,"Molecular diagnosis of microbial copathogens with influenza A(H1N1)pdm09 in Oaxaca, Mexico",http://dx.doi.org/10.2147/RRTM.S144075,PMC6047622,30050355,CC BY-NC,"BACKGROUND: Multiple factors have been associated with the severity of infection by influenza A(H1N1)pdm09. These include H1N1 cases with proven coinfections showing clinical association with bacterial contagions. PURPOSE: The objective was to identify H1N1 and copathogens in the Oaxaca (Mexico) population. A cross-sectional survey was conducted from 2009 to 2012. A total of 88 study patients with confirmed H1N1 by quantitative RT-PCR were recruited. METHODS: Total nucleic acid from clinical samples of study patients was analyzed using a TessArray RPM-Flu microarray assay to identify other respiratory pathogens. RESULTS: High prevalence of copathogens (77.3%; 68 patients harbored one to three pathogens), predominantly from Streptococcus, Haemophilus, Neisseria, and Pseudomonas, were detected. Three patients (3.4%) had four or five respiratory copathogens, whereas others (19.3%) had no copathogens. Copathogenic occurrence with Staphylococcus aureus was 5.7%, Coxsackie virus 2.3%, Moraxella catarrhalis 1.1%, Klebsiella pneumoniae 1.1%, and parainfluenza virus 3 1.1%. The number of patients with copathogens was four times higher to those with H1N1 alone (80.68% and 19.32%, respectively). Four individuals (4.5%; two males, one female, and one infant) who died due to H1N1 were observed to have harbored such copathogens as Streptococcus, Staphylococcus, Haemophilus, and Neisseria. CONCLUSION: In summary, copathogens were found in a significant number (>50%) of cases of influenza in Oaxaca. Timely detection of coinfections producing increased acuity or severity of disease and treatment of affected patients is urgently needed.",2018 Apr 6,"['Ramírez-Palacios, Luis Román', 'Reséndez-Pérez, Diana', 'Rodríguez-Padilla, Maria Cristina', 'Saavedra-Alonso, Santiago', 'Real-Najarro, Olga', 'Fernández-Santos, Nadia A', 'Rodriguez Perez, Mario A']",Res Rep Trop Med,,,True
55eb127fae1e7e297c11baca53a758cac2a77329,PMC,The Functional Properties of Preserved Eggs: From Anti-cancer and Anti-inflammatory Aspects,http://dx.doi.org/10.5851/kosfa.2018.38.3.615,PMC6048375,30018504,CC BY-NC,"Preserved egg, a kind of alkaline-fermented food, is a traditional egg product in China. Here, we investigated the nutritional functions of preserved eggs by in vivo and in vitro experiments. The results of in vivo studies showed that the levels of triglycerides (TG), total cholesterol (TCHO) and low-density lipoprotein cholesterol/high density lipoprotein cholesterol (LDL-C/HDL-C) were significantly decreased (p<0.05) in the liver of rats treated with preserved eggs. Meanwhile, the levels of two important cancer markers, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were also significantly decreased (p<0.05) in treated rats. In vitro studies were performed on Caco-2 cells, a human epithelial colorectal adenocarcinoma cell line. It demonstrated that the gastrointestinal (GI) digests of preserved eggs significantly accelerated (p<0.05) the apoptosis by upregulating caspase-3 in the Caco-2 cells. Besides, after treated with preserved eggs, the half maximal inhibitory concentration (IC50) of preserved eggs digests to Caco-2 cells was 5.75 mg/mL, indicating the significant inhibition of cell proliferation provided by preserved eggs (p<0.05). The results shown in this study demonstrated that preserved eggs may be a novel functional food involved with antilipemic, anti-inflammatory activity as well as the effect on accelarating the apoptosis of Caco-2 cells.",2018 Jul 31,"['Mao, Changyi', 'Yu, Zhihui', 'Li, Chengliang', 'Jin, Yongguo', 'Ma, Meihu']",Korean J Food Sci Anim Resour,,,True
05af85c50dd5c80a25fc3dd985d31f0d563d0019,PMC,A systematic review on silver nanoparticles-induced cytotoxicity: Physicochemical properties and perspectives,http://dx.doi.org/10.1016/j.jare.2017.10.008,PMC6057238,30046482,CC BY-NC-ND,"With the development of nanotechnology, silver nanoparticles (Ag-NPs) have become one of the most in-demand nanoparticles owing to their exponential number of uses in various sectors. The increased use of Ag-NPs-enhanced products may result in an increased level of toxicity affecting both the environment and living organisms. Several studies have used different model cell lines to exhibit the cytotoxicity of Ag-NPs, and their underlying molecular mechanisms. This review aimed to elucidate different properties of Ag-NPs that are responsible for the induction of cellular toxicity along with the critical mechanism of action and subsequent defense mechanisms observed in vitro. Our results show that the properties of Ag-NPs largely vary based on the diversified synthesis processes. The physiochemical properties of Ag-NPs (e.g., size, shape, concentration, agglomeration, or aggregation interaction with a biological system) can cause impairment of mitochondrial function prior to their penetration and accumulation in the mitochondrial membrane. Thus, Ag-NPs exhibit properties that play a central role in their use as biocides along with their applicability in environmental cleaning. We herein report a current review of the synthesis, applicability, and toxicity of Ag-NPs in relation to their detailed characteristics.",2017 Nov 2,"['Akter, Mahmuda', 'Sikder, Md. Tajuddin', 'Rahman, Md. Mostafizur', 'Ullah, A.K.M. Atique', 'Hossain, Kaniz Fatima Binte', 'Banik, Subrata', 'Hosokawa, Toshiyuki', 'Saito, Takeshi', 'Kurasaki, Masaaki']",J Adv Res,,,False
8c183a5df571437f64c3dd78c8e7f5999de86cdf,PMC,"Expanding Patient Access to Investigational New Drugs: Overview of Intermediate and Widespread Treatment Investigational New Drugs, and Emergency Authorization in Public Health Emergencies",http://dx.doi.org/10.1016/j.jacbts.2018.02.001,PMC6058931,30062226,CC BY-NC-ND,"Individual patients with life-threatening or severely debilitating diseases can petition the U.S. Food and Drug Administration (FDA) through their physicians to have expanded access (EA) to drugs that are in clinical trials but have not reached full FDA approval (the “single-patient” investigational new drug [IND] application). Additionally, recent state and federal laws—so-called “right to try legislation”—allow patients to approach drug companies directly for access prior to FDA approval. While these pathways provide potential access for individual patients to investigational drugs, different EA pathways permit entire groups of certain patients to access investigational drugs prior to FDA approval. This review focuses on special categories of EA INDs intended for multiple patients—the intermediate-group IND and the widespread-treatment IND—as well as emergency authorization for use of investigational drugs and biological products (e.g., vaccines) in public health emergencies.",2018 Jun 25,"Van Norman, Gail A.",JACC Basic Transl Sci,,,False
1eea683566ec30963f071a37deba6dde8b06ad57,PMC,"Expanding Patient Access to Investigational New Drugs: Overview of Intermediate and Widespread Treatment Investigational New Drugs, and Emergency Authorization in Public Health Emergencies",http://dx.doi.org/10.1016/j.jacbts.2018.02.001,PMC6058931,30062226,CC BY-NC-ND,"Individual patients with life-threatening or severely debilitating diseases can petition the U.S. Food and Drug Administration (FDA) through their physicians to have expanded access (EA) to drugs that are in clinical trials but have not reached full FDA approval (the “single-patient” investigational new drug [IND] application). Additionally, recent state and federal laws—so-called “right to try legislation”—allow patients to approach drug companies directly for access prior to FDA approval. While these pathways provide potential access for individual patients to investigational drugs, different EA pathways permit entire groups of certain patients to access investigational drugs prior to FDA approval. This review focuses on special categories of EA INDs intended for multiple patients—the intermediate-group IND and the widespread-treatment IND—as well as emergency authorization for use of investigational drugs and biological products (e.g., vaccines) in public health emergencies.",2018 Jun 25,"Van Norman, Gail A.",JACC Basic Transl Sci,,,False
3e213ce275307f241723cf26bcb756dcba2a6b5b,PMC,Wobbling Forth and Drifting Back: The Evolutionary History and Impact of Bacterial tRNA Modifications,http://dx.doi.org/10.1093/molbev/msy110,PMC6063277,29846694,CC BY-NC,"Along with tRNAs, enzymes that modify anticodon bases are a key aspect of translation across the tree of life. tRNA modifications extend wobble pairing, allowing specific (“target”) tRNAs to recognize multiple codons and cover for other (“nontarget”) tRNAs, often improving translation efficiency and accuracy. However, the detailed evolutionary history and impact of tRNA modifying enzymes has not been analyzed. Using ancestral reconstruction of five tRNA modifications across 1093 bacteria, we show that most modifications were ancestral to eubacteria, but were repeatedly lost in many lineages. Most modification losses coincided with evolutionary shifts in nontarget tRNAs, often driven by increased bias in genomic GC and associated codon use, or by genome reduction. In turn, the loss of tRNA modifications stabilized otherwise highly dynamic tRNA gene repertoires. Our work thus traces the complex history of bacterial tRNA modifications, providing the first clear evidence for their role in the evolution of bacterial translation.",2018 Aug 28,"['Diwan, Gaurav D', 'Agashe, Deepa']",Mol Biol Evol,,,True
bd0454b89ded3f6af56759f3ad276034f5c8de17,PMC,Detection and genetic characterization of Mamastrovirus 5 from Brazilian dogs,http://dx.doi.org/10.1016/j.bjm.2017.09.008,PMC6066731,29456114,CC BY-NC-ND,"Mamastrovirus 5 (MAstV5), belonging to the Astroviridae (AstV) family, previously known as canine astrovirus or astrovirus-like particles, has been reported in several countries to be associated with viral enteric disease in dogs since the 1980s. Astroviruses have been detected in fecal samples from a wide variety of mammals and birds that are associated with gastroenteritis and extra enteric manifestations. In the present study, RT-PCR was used to investigate the presence of MAstV5 in 269 dog fecal samples. MAstV5 was detected in 26% (71/269) of the samples. Interestingly, all MAstV5-positive samples derived from dogs displaying clinical signs suggestive of gastroenteritis, other enteric viruses were simultaneously detected (canine parvovirus, canine distemper virus, canine coronavirus, canine adenovirus and canine rotavirus). Based on genomic sequence analysis of MAstV5 a novel classification of the species into four genotypes, MAstV5a-MAstV5d, is proposed. Phylogenetic analyses based on the ORF2 amino acid sequences, samples described herein grouped into the putative genotype ‘a’ closed related with Chinese samples. Other studies are required to attempt the clinical and antigenic implications of these astrovirus genotypes in dogs.",2018 Feb 2,"['Alves, Christian D.B.T.', 'Budaszewski, Renata F.', 'Torikachvili, Marcela', 'Streck, André F.', 'Weber, Matheus N.', 'Cibulski, Samuel P.', 'Ravazzolo, Ana P.', 'Lunge, Vagner R.', 'Canal, Cláudio W.']",Braz J Microbiol,,,False
4ee0f8eb93dda0ff3512556fbb784c3859cc156f,PMC,Jet set pets: examining the zoonosis risk in animal import and travel across the European Union,http://dx.doi.org/10.2147/VMRR.S62059,PMC6067792,30101093,CC BY-NC,"Ownership of companion animals or pets is popular throughout the world. Unfortunately, such animals are susceptible to and potential reservoirs of zoonotic pathogens. Close proximity to and contact with pets can lead to human infections. The distribution of zoonotic diseases associated with companion animals such as dogs and cats is not uniform around the world, and moving animals between regions, countries, and continents carries with it the risk of relocating the pathogens they might harbor. Critical among these zoonotic diseases are rabies, echinococcosis, and leishmania. In addition, the protozoan parasites, Toxoplasma gondii and Giardia duodenalis, are also significant agents for human disease of pet origin. Considerable effort is applied to controlling movements of companion animals, particularly dogs, into the European Union. However, free movement of people and their pets within the European Union is a risk factor for the translocation of diseases and their vectors. This review considers the current distribution of some of these diseases, the risks associated with pet travel, and the controls implemented within Europe to prevent the free movement of zoonotic pathogens.",2014 Dec 18,"['Fooks, Anthony R', 'Johnson, Nicholas']",Vet Med (Auckl),,,True
2041dc24bd4022a90b0b441ed6f1024f3e16dc77,PMC,A long-term animal experiment indicating persistent infection of bovine coronavirus in cattle,http://dx.doi.org/10.1292/jvms.18-0050,PMC6068295,29780039,CC BY-NC-ND,"A long-term animal experiment involving inoculation with bovine coronavirus (BCoV) was conducted to verify its persistent infection in cattle. Three colostrum-deprived Holstein calves were housed separately in individual rooms of a high-containment facility and inoculated with the BCoV strain Kumamoto/1/07. Until the end of the experiment (1,085, 700 and 280 days, respectively), viral RNAs were detected sporadically by RT-PCR and nested PCR from plasma, nasal discharge, and feces. Seroconversion and titer changes were validated by hemagglutination inhibition tests and neutralization tests. Among the samples, nasal discharge showed a higher viral positivity than feces, which seemed to be associated with positive detection in the plasma. These data demonstrate the existence of persistent infection of BCoV in the respiratory tissues of cattle.",2018 Jul 18,"['KANNO, Toru', 'ISHIHARA, Ryoko', 'HATAMA, Shinichi', 'UCHIDA, Ikuo']",J Vet Med Sci,,,True
3ef8cc40a38577b24aab94171acf6959598b32c7,PMC,Detection of Sirtuin-1 protein expression in peripheral blood leukocytes in dogs,http://dx.doi.org/10.1292/jvms.17-0499,PMC6068298,29760313,CC BY-NC-ND,"Sirtuin-1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD(+))-dependent histone deacetylase with a large number of protein substrates. It has attracted a lot of attention in association with extending lifespan. The objective of this study was to enable the evaluation of SIRT1 expression in peripheral blood mononuclear cells (PBMCs) from dogs by flow cytometry. Three transcript variants were amplified from PBMCs by reverse transcription PCR and the nucleotide sequences were analyzed. On the basis of deduced amino acid sequence, a monoclonal antibody against human SIRT1, 1F3, was selected to detect canine SIRT1. Canine SIRT1 in peripheral blood mononuclear cells was successfully detected by western blotting using this antibody. Intracellular canine SIRT1 was also detected in permeabilized 293T cells transfected with a canine SIRT1 expression plasmid by flow cytometry using this antibody. SIRT1 was detected in all leukocyte subsets including lymphocytes, granulocytes and monocytes. The expression level was markedly different among individual dogs. These results indicated that the method applied in this study is useful for evaluating canine SIRT1 levels in PBMCs from dogs.",2018 Jul 11,"['YOSHIMURA, Kuniko', 'MATSUU, Aya', 'SASAKI, Kai', 'MOMOI, Yasuyuki']",J Vet Med Sci,,,True
40c0532640a8bb9d9a0aac07d017d5982af33fdb,PMC,Mutation of the S and 3c genes in genomes of feline coronaviruses,http://dx.doi.org/10.1292/jvms.17-0704,PMC6068308,29769478,CC BY-NC-ND,"Feline coronavirus (FCoV) is classified into two biotypes based on its pathogenicity in cats: a feline enteric coronavirus of low pathogenicity and a highly virulent feline infectious peritonitis virus. It has been suspected that FCoV alters its biotype via mutations in the viral genome. The S and 3c genes of FCoV have been considered the candidates for viral pathogenicity conversion. In the present study, FCoVs were analyzed for the frequency and location of mutations in the S and 3c genes from faecal samples of cats in an animal shelter and the faeces, effusions, and tissues of cats that were referred to veterinary hospitals. Our results indicated that approximately 95% FCoVs in faeces did not carry mutations in the two genes. However, 80% FCoVs in effusion samples exhibited mutations in the S and 3c genes with remainder displaying a mutation in the S or 3c gene. It was also suggested that mutational analysis of the 3c gene could be useful for studying the horizontal transmission of FCoVs in multi-cat environments.",2018 Jul 17,"['OGUMA, Keisuke', 'OHNO, Megumi', 'YOSHIDA, Mayuko', 'SENTSUI, Hiroshi']",J Vet Med Sci,,,True
c383985e1fd30909b668a5df2929fab31d6e76b7,PMC,Mutation of the S and 3c genes in genomes of feline coronaviruses,http://dx.doi.org/10.1292/jvms.17-0704,PMC6068308,29769478,CC BY-NC-ND,"Feline coronavirus (FCoV) is classified into two biotypes based on its pathogenicity in cats: a feline enteric coronavirus of low pathogenicity and a highly virulent feline infectious peritonitis virus. It has been suspected that FCoV alters its biotype via mutations in the viral genome. The S and 3c genes of FCoV have been considered the candidates for viral pathogenicity conversion. In the present study, FCoVs were analyzed for the frequency and location of mutations in the S and 3c genes from faecal samples of cats in an animal shelter and the faeces, effusions, and tissues of cats that were referred to veterinary hospitals. Our results indicated that approximately 95% FCoVs in faeces did not carry mutations in the two genes. However, 80% FCoVs in effusion samples exhibited mutations in the S and 3c genes with remainder displaying a mutation in the S or 3c gene. It was also suggested that mutational analysis of the 3c gene could be useful for studying the horizontal transmission of FCoVs in multi-cat environments.",2018 Jul 17,"['OGUMA, Keisuke', 'OHNO, Megumi', 'YOSHIDA, Mayuko', 'SENTSUI, Hiroshi']",J Vet Med Sci,,,False
29445ecd280247f79d6cebe0c3b4d06796e72eb9,PMC,Isolation and characterization of Korean porcine deltacoronavirus strain KNU16-07,http://dx.doi.org/10.4142/jvs.2018.19.4.577,PMC6070590,29695146,CC BY-NC,"Porcine deltacoronavirus (PDCoV) has emerged in several pig-raising countries and has been a causative pathogen associated with diarrheal diseases in South Korea since 2014. In the present study, we were able to isolate and cultivate a Korean PDCoV strain (KNU16-07) in cell culture and investigate its pathogenicity. PDCoV-inoculated piglets showed watery diarrhea accompanied by acute enteritis in the natural host. Sequencing analysis demonstrated the genetic stability of KNU16-07 for at least thirty serial passages.",2018 Jul 26,"['Jang, Guehwan', 'Kim, Seong-Hee', 'Lee, Yoo Jin', 'Kim, Seungjoon', 'Lee, Du Sik', 'Lee, Kyoung-Ki', 'Lee, Changhee']",J Vet Sci,,,True
d32ec6ce72c16f7fbedc8ac60fbdc9f8c74c6de4,PMC,CXCL9 promotes prostate cancer progression through inhibition of cytokines from T cells,http://dx.doi.org/10.3892/mmr.2018.9152,PMC6072144,29901197,CC BY-NC-ND,"Chemokines have been demonstrated to serve an important role in a variety of diseases, particularly in tumor progression. There have been numerous studies that have reported that T cells serve major roles in tumor progression. However, the function of CXC motif chemokine ligand 9 (CXCL9) in prostate cancer remains unknown. The present study aimed to investigate the role of CXCL9 in prostate cancer. A prostate cancer mouse model was generated by treating C57/BL-6 and B6.Cg-Selplgtm1Fur/J mice with 3,2′-dimethyl 4-aminobiphenyl (DMAB). Hematoxylin and eosin staining detected the histopathological alterations of mouse prostate tissues. Immunohistochemistry (IHC) staining determined cell proliferation of the mice. Flow cytometry was used to detect the alterations of T cells in C57+DMAB or CXCL9+DMAB mice. Immunofluorescence revealed that there was positive expression of interleukin-6 (IL-6) and transforming growth factor (TGF)-β in the mouse tissues. The survival rates of C57+DMAB and CXCL9+DMAB mice was analyzed. The association of CXCL9 expression and clinical stages was also evaluated. Results revealed that prostate cancer pathology and cell proliferation in CXCL9+DMAB mice were significantly greater compared with the C57+DMAB mice. Compared with C57+DMAB mice, the number of T cells in peripheral blood and spleen of CXCL9+DMAB mice was significantly reduced. IHC demonstrated that the expression of IL-6 and TGF-β was significantly downregulated in the CXCL9+DMAB mice. The survival rate of CXCL9+DMAB mice was significantly decreased compared with the C57+DMAB mice. In addition, reverse transcription-quantitative polymerase chain reaction analysis demonstrated that CXCL9 mRNA expression in clinical samples was positively associated with clinical pathological stages of prostate cancer. In conclusion, CXCL9 may promote prostate cancer progression via inhibition of cytokines from T cells.",2018 Aug 11,"['Tan, Shanfeng', 'Wang, Kai', 'Sun, Fuguang', 'Li, Yang', 'Gao, Yisheng']",Mol Med Rep,,,True
06f075e64c8861491ea4de2f98b606866f54a752,PMC,Acute myocarditis associated with novel Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.5144/0256-4947.2016.78,PMC6074274,26922692,CC BY-NC-ND,"The novel Middle East respiratory syndrome coronavirus (MERS-CoV) has been identified as a cause of pneumonia; however, it has not been reported as a cause of acute myocarditis. A 60-year-old man presented with pneumonia and congestive heart failure. On the first day of admission, he was found to have an elevated troponin-I level and severe global left ventricular systolic dysfunction on echocardiography. The serum creatinine level was found mildly elevated. Chest radiography revealed in the lower lung fields accentuated bronchovascular lung markings and multiple small patchy opacities. Laboratory tests were negative for viruses known to cause myocarditis. Sputum sample was positive for MERS-CoV. Cardiovascular magnetic resonance revealed evidence of acute myocarditis. The patient had all criteria specified by the International Consensus Group on CMR in Myocarditis that make a clinical suspicion for acute myocarditis. This was the first case that demonstrated that MERS-CoV may cause acute myocarditis and acute-onset heart failure.",2016 Jan-Feb,"Alhogbani, Tariq",Ann Saudi Med,,,True
fb02396b27e7eba6cd6e52fec15c040a98cc0d48,PMC,"Descriptive epidemiology and characteristics of confirmed cases of Middle East respiratory syndrome coronavirus infection in the Makkah Region of Saudi Arabia, March to June 2014",http://dx.doi.org/10.5144/0256-4947.2015.203,PMC6074457,26409794,CC BY-NC-ND,"BACKGROUND AND OBJECTIVES: Describe the epidemiology and characteristics of Middle East respiratory syndrome coronavirus (MERS-CoV), which are essential for control and treatment. METHODS: We conducted a retrospective review of all cases of MERS-CoV reported in four cities of the Makkah Region from March to June 2014. Exposure factors and comorbid conditions were analyzed using Epi Info. RESULTS: Analysis of the 261 cases revealed that the incidence peaked in mid-April 2014 and the fatality rate was 42%. Cough, fever, radiological evidence of pneumonia, and shortness of breath were identified as significant risk factors for a diagnosis of MER-CoV infection. Healthcare workers (HCWs) are at a higher risk of acquiring MERS-CoV than non-HCWs. Males in Jeddah are at higher risk due to greater outdoor exposure while females in Taif are at higher risk due to domestic caregiving. Filipino nurses are at highest risk among all HCWs. CONCLUSION: The findings indicate the need to screen all contacts of HCWs to improve MERS control and form public–private partnerships to investigate the true burden of MERS.",2015 May-Jun,"['Noorwali, AbdulSalam A.', 'Turkistani, AbdulHafiz M.', 'Asiri, Sari I.', 'Trabulsi, Fadel A.', 'Alwafi, Osama M.', 'Alzahrani, Saud H.', 'Rashid, Muhammad M.', 'Hegazy, Safwat A.', 'Alzaydi, Mohammed D.', 'Bawakid, Khalid O.']",Ann Saudi Med,,,True
b4c159232c0fd198ffac37ccdf30ee4fc6f24518,PMC,Middle Eastern Respiratory Syndrome Corona Virus (MERS CoV): case reports from a tertiary care hospital in Saudi Arabia,http://dx.doi.org/10.5144/0256-4947.2014.396,PMC6074560,25827696,CC BY-NC-ND,"BACKGROUND AND OBJECTIVES: Middle Eastern respiratory syndrome caused by novel coronavirus (MERS CoV) has been a major public health challenge since it was first described in 2012 in Saudi Arabia. So far, there is no effective treatment for this serious illness, which features a high mortality rate. We report an initial experience of the use of ribavirin and interferon (IFN)-α2b in the management of MERS CoV at a tertiary care hospital. DESIGN AND SETTINGS: A case series of 6 patients admitted with a confirmed diagnosis of MERS CoV were treated with ribavirin and IFN-α2b in addition to supportive management. The patients’ demographics, clinical parameters, and outcomes were recorded. Fifty-four close contacts of these patients were screened for MERS CoV. METHODS: Six patients with MERS CoV infection were included in this study. Four cases featured symptomatic disease, including pneumonia and respiratory failure, while 2 were asymptomatic close contacts of the MERS CoV patients. The MERS CoV infection was confirmed by reverse transcription–polymerase chain reaction detection of the consensus viral RNA targets upstream of the E gene (UPE) and open reading frame (ORF1b) on a sputum sample. The patients’ demographics, comorbid conditions, time to diagnosis and initiation of treatment, and clinical outcomes were recorded. RESULTS: Three out of 6 patients who had comorbid conditions died during the study period, while 3 had successful outcomes. The diagnosis and treatment was delayed by an average of 15 days in those patients who died. Only 2 close contacts out of the 54 screened (3.7%) were positive for MERS CoV. CONCLUSION: Treatment with ribavirin and IFN-α2b may be effective in patients infected with MERS CoV. There appears to be a low infectivity rate among close contacts of MERS CoV patients.",2014 Sep-Oct,"['Khalid, Mohammad', 'Khan, Basha', 'Al Rabiah, Fahad', 'Alismaili, Ruwaida', 'Saleemi, Sarfraz', 'Rehan-Khaliq, Agha Muhammad', 'Weheba, Ihab', 'Al Abdely, Hail', 'Halim, Magid', 'Nadri, Quaid Johar', 'Al Dalaan, Abdullah Mohsin', 'Zeitouni, Mohamed', 'Butt, Taimur', 'Al Mutairy, Eid']",Ann Saudi Med,,,True
ebfe84418eef9017bbf2bdb93d8bebdb3eef8eac,PMC,Middle East Respiratory Syndrome Coronavirus (MERS-CoV): A Perpetual Challenge,http://dx.doi.org/10.5144/0256-4947.2013.427,PMC6074883,24188935,CC BY-NC-ND,,2013 Sep-Oct,"['Al Hajjar, Sami', 'Memish, Ziad A.', 'McIntosh, Kenneth']",Ann Saudi Med,,,True
aad0a6df3e62a8279846dd17a8d09675f2b14397,PMC,The influence of strain due to individual risk factors and social risk factors on depressive symptoms and suicidality-a population-based study in Korean adults: A STROBE-compliant article,http://dx.doi.org/10.1097/MD.0000000000011358,PMC6076168,29979418,CC BY-NC-ND,"Suicide is the outcome of the interaction of biological, personal, and social risk factors. The purpose of this study was to verify the effects of strain due to individual risk factors and social risk factors on suicidality, and the mediating effect of depressive symptoms in relationship between strain related to individual risk factors and social risk factors and suicidality. The data from sociopsychological anxiety survey of Korea society conducted by the Korea Institute for Health and Social Affairs in 2015 were used in verifying the model. We analyzed the data of 7000 adults aged 19 to 79 years using Structural Equation Modeling. Strain due to individual risk factors was positively related to depressive symptoms and suicidality. Interestingly, strain induced by social risk factors was positively associated with depressive symptoms and suicidality. Social support is significantly associated with depressive symptoms and suicidality. Depressive symptoms directly affected suicidality. In addition, strain due to individual risk factors and social risk factors indirectly affected suicidality mediating depressive symptoms. These findings suggest that not only individual efforts such as social interaction and depression prevention but also government efforts such as preparation for aging may be needed to decrease suicide rate.",2018 Jul 6,"Sung-Man, Bae",Medicine (Baltimore),,,True
14f66845d5028f06204e3bc528e14e7dddd5b341,PMC,Investigating Tick-borne Flaviviral-like Particles as a Delivery System for Gene Therapy,http://dx.doi.org/10.1016/j.curtheres.2017.10.003,PMC6076373,30093925,CC BY-NC-ND,"BACKGROUND: Research on the biogenesis of tick-borne encephalitis virus (TBEV) would benefit gene therapy. Due to specific arrangements of genes along the TBEV genome, its viral-like particles (VLPs) could be exploited as shuttles to deliver their replicon, which carries therapeutic genes, to immune system cells. OBJECTIVE: To develop a flaviviral vector for gene delivery as a part of gene therapy research that can be expressed in secretable VLP suicidal shuttles and provide abundant unique molecular and structural data supporting this gene therapy concept. METHOD: TBEV structural gene constructs of a Swedish Torö strain were cloned into plasmids driven by the promoters CAG and CMV and then transfected into various cell lines, including COS-1 and BHK-21. Time-course sampling of the cells, culture fluid, cell lysate supernatant, and pellet specimens were performed. Western blotting and electron microscopy analyses of collected specimens were used to investigate molecular and structural processing of TBEV structural proteins. RESULTS: Western blotting analysis showed differences between promoters in directing the gene expression of the VLPs constructs. The premature flaviviral polypeptides as well as mature VLPs could be traced. Using electron microscopy, the premature and mature VLP accumulation in cellular compartments—and also endoplasmic reticulum proliferation as a virus factory platform—were observed in addition to secreted VLPs. CONCLUSIONS: The abundant virologic and cellular findings in this study show the natural processing and safety of inserting flaviviral structural genes into suicidal VLP shuttles. Thus, we propose that these VLPs are a suitable gene delivering system model in gene therapy.",2017 Oct 16,"['Neddermeyer, Anne H.', 'Hultenby, Kjell', 'Paidikondala, Maruthibabu', 'Schuchman, Ryan M.', 'Bidokhti, Mehdi R.M.']",Curr Ther Res Clin Exp,,,False
f4b79eb20b36c30c9b7965f5ae6252f4a5425c27,PMC,Investigating Tick-borne Flaviviral-like Particles as a Delivery System for Gene Therapy,http://dx.doi.org/10.1016/j.curtheres.2017.10.003,PMC6076373,30093925,CC BY-NC-ND,"BACKGROUND: Research on the biogenesis of tick-borne encephalitis virus (TBEV) would benefit gene therapy. Due to specific arrangements of genes along the TBEV genome, its viral-like particles (VLPs) could be exploited as shuttles to deliver their replicon, which carries therapeutic genes, to immune system cells. OBJECTIVE: To develop a flaviviral vector for gene delivery as a part of gene therapy research that can be expressed in secretable VLP suicidal shuttles and provide abundant unique molecular and structural data supporting this gene therapy concept. METHOD: TBEV structural gene constructs of a Swedish Torö strain were cloned into plasmids driven by the promoters CAG and CMV and then transfected into various cell lines, including COS-1 and BHK-21. Time-course sampling of the cells, culture fluid, cell lysate supernatant, and pellet specimens were performed. Western blotting and electron microscopy analyses of collected specimens were used to investigate molecular and structural processing of TBEV structural proteins. RESULTS: Western blotting analysis showed differences between promoters in directing the gene expression of the VLPs constructs. The premature flaviviral polypeptides as well as mature VLPs could be traced. Using electron microscopy, the premature and mature VLP accumulation in cellular compartments—and also endoplasmic reticulum proliferation as a virus factory platform—were observed in addition to secreted VLPs. CONCLUSIONS: The abundant virologic and cellular findings in this study show the natural processing and safety of inserting flaviviral structural genes into suicidal VLP shuttles. Thus, we propose that these VLPs are a suitable gene delivering system model in gene therapy.",2017 Oct 16,"['Neddermeyer, Anne H.', 'Hultenby, Kjell', 'Paidikondala, Maruthibabu', 'Schuchman, Ryan M.', 'Bidokhti, Mehdi R.M.']",Curr Ther Res Clin Exp,,,False
03d003f7c962aa4f0394e79f38a332662105cdb3,PMC,Xylitol for the prevention of acute otitis media episodes in children aged 2–4 years: protocol for a pragmatic randomised controlled trial,http://dx.doi.org/10.1136/bmjopen-2017-020941,PMC6078241,30082349,CC BY-NC,"INTRODUCTION: Xylitol (or ‘birch sugar’) is a naturally occurring sugar with antibacterial properties that has been used as a natural non-sugar sweetener in chewing gums, confectionery, toothpaste and medicines. In this preventative randomised trial, xylitol will be tested for the prevention of acute otitis media (AOM), a common and costly condition in young children. The primary outcome will be the incidence of AOM. Secondary outcomes will include upper respiratory tract infections (URTIs) and dental caries. METHODS AND ANALYSIS: This study will be a pragmatic, blinded (participant and parents, practitioners and analyst), two-armed superiority, placebo-controlled randomised trial with 1:1 allocation, stratified by clinical site. The trial will be conducted in the 11 primary care group practices participating in the TARGet Kids! research network in Canada. Eligible participants between the ages of 2–4 years will be randomly assigned to the intervention arm of regular xylitol syrup use or the control arm of regular sorbitol use for 6 months. We expect to recruit 236 participants, per treatment arm, to detect a 20% relative risk reduction in AOM episodes. AOM will be identified through chart review. The secondary outcomes of URTIs and dental caries will be identified through monthly phone calls with specified questions. ETHICS AND DISSEMINATION: Ethics approval from the Research Ethics Boards at the Hospital for Sick Children and St. Michael’s Hospital has been obtained for this study and also for the TARGet Kids! research network. Results will be submitted for publication to a peer-reviewed journal and will be discussed with decision makers. TRIAL REGISTRATION NUMBER: NCT03055091; Pre-results.",2018 Aug 5,"['Persaud, Nav', 'Laupacis, Andreas', 'Azarpazhooh, Amir', 'Birken, Catherine', 'Hoch, Jeffrey S', 'Isaranuwatchai, Wanrudee', 'Maguire, Jonathan L', 'Mamdani, Muhammad M', 'Thorpe, Kevin', 'Allen, Christopher', 'Mason, Dalah', 'Kowal, Christine', 'Bazeghi, Farnaz', 'Parkin, Patricia', None]",BMJ Open,,,True
77dd0ff052179336391f3256d7a4afb57a71a6b2,PMC,Xylitol for the prevention of acute otitis media episodes in children aged 2–4 years: protocol for a pragmatic randomised controlled trial,http://dx.doi.org/10.1136/bmjopen-2017-020941,PMC6078241,30082349,CC BY-NC,"INTRODUCTION: Xylitol (or ‘birch sugar’) is a naturally occurring sugar with antibacterial properties that has been used as a natural non-sugar sweetener in chewing gums, confectionery, toothpaste and medicines. In this preventative randomised trial, xylitol will be tested for the prevention of acute otitis media (AOM), a common and costly condition in young children. The primary outcome will be the incidence of AOM. Secondary outcomes will include upper respiratory tract infections (URTIs) and dental caries. METHODS AND ANALYSIS: This study will be a pragmatic, blinded (participant and parents, practitioners and analyst), two-armed superiority, placebo-controlled randomised trial with 1:1 allocation, stratified by clinical site. The trial will be conducted in the 11 primary care group practices participating in the TARGet Kids! research network in Canada. Eligible participants between the ages of 2–4 years will be randomly assigned to the intervention arm of regular xylitol syrup use or the control arm of regular sorbitol use for 6 months. We expect to recruit 236 participants, per treatment arm, to detect a 20% relative risk reduction in AOM episodes. AOM will be identified through chart review. The secondary outcomes of URTIs and dental caries will be identified through monthly phone calls with specified questions. ETHICS AND DISSEMINATION: Ethics approval from the Research Ethics Boards at the Hospital for Sick Children and St. Michael’s Hospital has been obtained for this study and also for the TARGet Kids! research network. Results will be submitted for publication to a peer-reviewed journal and will be discussed with decision makers. TRIAL REGISTRATION NUMBER: NCT03055091; Pre-results.",2018 Aug 5,"['Persaud, Nav', 'Laupacis, Andreas', 'Azarpazhooh, Amir', 'Birken, Catherine', 'Hoch, Jeffrey S', 'Isaranuwatchai, Wanrudee', 'Maguire, Jonathan L', 'Mamdani, Muhammad M', 'Thorpe, Kevin', 'Allen, Christopher', 'Mason, Dalah', 'Kowal, Christine', 'Bazeghi, Farnaz', 'Parkin, Patricia', None]",BMJ Open,,,True
56a1994b4eaa93bba25210697efc42a5445c7cd5,PMC,Xylitol for the prevention of acute otitis media episodes in children aged 2–4 years: protocol for a pragmatic randomised controlled trial,http://dx.doi.org/10.1136/bmjopen-2017-020941,PMC6078241,30082349,CC BY-NC,"INTRODUCTION: Xylitol (or ‘birch sugar’) is a naturally occurring sugar with antibacterial properties that has been used as a natural non-sugar sweetener in chewing gums, confectionery, toothpaste and medicines. In this preventative randomised trial, xylitol will be tested for the prevention of acute otitis media (AOM), a common and costly condition in young children. The primary outcome will be the incidence of AOM. Secondary outcomes will include upper respiratory tract infections (URTIs) and dental caries. METHODS AND ANALYSIS: This study will be a pragmatic, blinded (participant and parents, practitioners and analyst), two-armed superiority, placebo-controlled randomised trial with 1:1 allocation, stratified by clinical site. The trial will be conducted in the 11 primary care group practices participating in the TARGet Kids! research network in Canada. Eligible participants between the ages of 2–4 years will be randomly assigned to the intervention arm of regular xylitol syrup use or the control arm of regular sorbitol use for 6 months. We expect to recruit 236 participants, per treatment arm, to detect a 20% relative risk reduction in AOM episodes. AOM will be identified through chart review. The secondary outcomes of URTIs and dental caries will be identified through monthly phone calls with specified questions. ETHICS AND DISSEMINATION: Ethics approval from the Research Ethics Boards at the Hospital for Sick Children and St. Michael’s Hospital has been obtained for this study and also for the TARGet Kids! research network. Results will be submitted for publication to a peer-reviewed journal and will be discussed with decision makers. TRIAL REGISTRATION NUMBER: NCT03055091; Pre-results.",2018 Aug 5,"['Persaud, Nav', 'Laupacis, Andreas', 'Azarpazhooh, Amir', 'Birken, Catherine', 'Hoch, Jeffrey S', 'Isaranuwatchai, Wanrudee', 'Maguire, Jonathan L', 'Mamdani, Muhammad M', 'Thorpe, Kevin', 'Allen, Christopher', 'Mason, Dalah', 'Kowal, Christine', 'Bazeghi, Farnaz', 'Parkin, Patricia', None]",BMJ Open,,,False
21f352715a39be03f1d5015303b7a1ea824cee9c,PMC,Xylitol for the prevention of acute otitis media episodes in children aged 2–4 years: protocol for a pragmatic randomised controlled trial,http://dx.doi.org/10.1136/bmjopen-2017-020941,PMC6078241,30082349,CC BY-NC,"INTRODUCTION: Xylitol (or ‘birch sugar’) is a naturally occurring sugar with antibacterial properties that has been used as a natural non-sugar sweetener in chewing gums, confectionery, toothpaste and medicines. In this preventative randomised trial, xylitol will be tested for the prevention of acute otitis media (AOM), a common and costly condition in young children. The primary outcome will be the incidence of AOM. Secondary outcomes will include upper respiratory tract infections (URTIs) and dental caries. METHODS AND ANALYSIS: This study will be a pragmatic, blinded (participant and parents, practitioners and analyst), two-armed superiority, placebo-controlled randomised trial with 1:1 allocation, stratified by clinical site. The trial will be conducted in the 11 primary care group practices participating in the TARGet Kids! research network in Canada. Eligible participants between the ages of 2–4 years will be randomly assigned to the intervention arm of regular xylitol syrup use or the control arm of regular sorbitol use for 6 months. We expect to recruit 236 participants, per treatment arm, to detect a 20% relative risk reduction in AOM episodes. AOM will be identified through chart review. The secondary outcomes of URTIs and dental caries will be identified through monthly phone calls with specified questions. ETHICS AND DISSEMINATION: Ethics approval from the Research Ethics Boards at the Hospital for Sick Children and St. Michael’s Hospital has been obtained for this study and also for the TARGet Kids! research network. Results will be submitted for publication to a peer-reviewed journal and will be discussed with decision makers. TRIAL REGISTRATION NUMBER: NCT03055091; Pre-results.",2018 Aug 5,"['Persaud, Nav', 'Laupacis, Andreas', 'Azarpazhooh, Amir', 'Birken, Catherine', 'Hoch, Jeffrey S', 'Isaranuwatchai, Wanrudee', 'Maguire, Jonathan L', 'Mamdani, Muhammad M', 'Thorpe, Kevin', 'Allen, Christopher', 'Mason, Dalah', 'Kowal, Christine', 'Bazeghi, Farnaz', 'Parkin, Patricia', None]",BMJ Open,,,False
0cf8f70367fc77ea444519b2d9ed108765edd25f,PMC,Acute fibrinous and organizing pneumonia,http://dx.doi.org/10.5144/0256-4947.2013.301,PMC6078531,23793436,CC BY-NC-ND,"A 45-year-old man presented with malaise, arthralgia, and dyspnea. The chest CT scan showed bilateral patchy consolidation in the lower lobes. A lung biopsy revealed intra-alveolar fibrin “balls” deposits and focal features of organizing pneumonia, both of which are typical pathological features of acute fibrinous and organizing pneumonia (AFOP). The patient had a good clinical course after treatment with prednisone. We report this case of idiopathic AFOP and review the published studies on this newly recognized clinicopathological entity that is still underdiagnosed and underreported.",2013 May-Jun,"['Al-Khouzaie, Thamer H.', 'Dawamneh, Mohamad F.', 'Hazmi, Albader M.']",Ann Saudi Med,,,True
d50ec2ab542eef07b9df564017f4c537e1c5d13a,PMC,The usefulness of hand washing during field training to prevent acute respiratory illness in a military training facility,http://dx.doi.org/10.1097/MD.0000000000011594,PMC6078659,30045292,CC BY-NC-ND,"Hand washing plays a key role in preventing respiratory infection in many clinical settings. However, its effectiveness in preventing acute respiratory illness (ARI) during field training in military training facilities has been not studied. A quasi-interventional study was performed to evaluate the prevalence of ARIs over 4 weeks in a Korean army training center in South Korea from January 2009 to February 2009. A total of 1291 recruits participating in military training for 4 weeks were randomly distributed to 2 battalions (one with 631 and the other with 660). After noticing there is a difference between the 2 battalions in terms of the development of ARIs at the end of 2 weeks of training, we conducted interviews with the battle commanders to determine factors that may be related to one battalion having a higher incidence of ARI. Thereafter, we performed an intervention, which consists of instructing the battalion having a higher incidence of ARI to implement field hand washing from the third week. Following the intervention, we compared the cumulative rate of ARI during 4 weeks of training. The interviews revealed that there were no major differences between the 2 battalions in terms of the training schedules, living environments, or indoor hand washing methods. However, there was difference in terms of hand washing during field training for the first 2 weeks; whereas one battalion (the early hand washing group) implemented hand washing during field training starting in the first week, the other battalion did not implement hand washing for the first 2 weeks but instead began in the third week (the late hand washing group). The cumulative incidence rate of ARI during 4 weeks of training was significantly lower in the early hand washing group (13.0%, 95% confidence interval [CI]: 10.6%–15.9%) than in the late hand washing group (28.0%, 95% CI, 24.7%–31.5%). Our study suggests that outdoor hand washing during field training may be an effective precaution for reducing ARI incidence among recruits participating in military training.",2018 Jul 27,"['Kim, Ho Seung', 'Ko, Ryoung Eun', 'Ji, Misuk', 'Lee, Ju-Hyung', 'Lee, Chang-Seop', 'Lee, Hyun']",Medicine (Baltimore),,,True
362b77d7f48903a4c2b808cd4edb9013b527e2a3,PMC,Laboratory epidemiology of respiratory viruses in a large children's hospital: A STROBE-compliant article,http://dx.doi.org/10.1097/MD.0000000000011385,PMC6078760,30045260,CC BY-NC,"Acute respiratory tract infection (ARTI) is the most common causes of outpatient visit and hospital admission for children. The study aimed to report epidemiological data on respiratory viruses in a university-affiliated children's hospital. The study was a retrospective study conducted in a university affiliated children's hospital from 2016 May to 2017 April. The results of all nasopharyngeal swab and sputum samples sent for the test for respiratory viruses (adenovirus, influenza A, influenza B, and respiratory syncytial virus) were extracted from the electronic healthcare records. Clinical characteristics were compared between groups with positive versus negative results for respiratory viruses. Multivariable regression models were employed by including age, gender, type of sample (swab vs sputum), source (emergency department vs others), and season to explore the independent factors associated with positive results for respiratory viruses. A total of 34,961 samples were identified during the study period. A total of 3102 (8.9%) samples were positive for adenovirus, 2811 (8.0%) were positive for influenza A, 3460 (9.9%) were positive for influenza B, and 4527 (13.0%) were positive for respiratory syncytial virus. The positive rate of adenovirus was highest in April (50.8%), and lowest in November (3%). The absolute number of positive samples for adenovirus was highest in June (n = 587) and April (n = 544). For the test of influenza A, age was independently associated with positive result. With 1 year increase in age, the odds of positive result increased by 12% (odds ratio [OR]: 1.12; 95% confidence interval [CI]: 1.11–1.13; P < .001). As compared with the autumn, the summer showed significantly lower rate of positive for RSV (OR: 0.49; 95% CI: 0.38–0.62; P < .001), whereas the winter had higher risk of positive result (OR: 3.88; 95% CI: 3.37–4.50; P < .001). The study reported epidemiological data on the prevalence of respiratory viruses in a large tertiary care children's hospital. Age, gender, type of sample, source, and season were associated with the positive rates for respiratory viruses.",2018 Jul 27,"['Ye, Sheng', 'Wang, Tianlin']",Medicine (Baltimore),,,True
aad248c894ac1b35e2adad9e23c9cf40dc3c20aa,PMC,Matrix stiffness modulates infection of endothelial cells by Listeria monocytogenes via expression of cell surface vimentin,http://dx.doi.org/10.1091/mbc.E18-04-0228,PMC6080647,29718765,CC BY-NC-SA,"Extracellular matrix stiffness (ECM) is one of the many mechanical forces acting on mammalian adherent cells and an important determinant of cellular function. While the effect of ECM stiffness on many aspects of cellular behavior has been studied previously, how ECM stiffness might mediate susceptibility of host cells to infection by bacterial pathogens is hitherto unexplored. To address this open question, we manufactured hydrogels of varying physiologically relevant stiffness and seeded human microvascular endothelial cells (HMEC-1) on them. We then infected HMEC-1 with the bacterial pathogen Listeria monocytogenes (Lm) and found that adhesion of Lm to host cells increases monotonically with increasing matrix stiffness, an effect that requires the activity of focal adhesion kinase (FAK). We identified cell surface vimentin as a candidate surface receptor mediating stiffness-dependent adhesion of Lm to HMEC-1 and found that bacterial infection of these host cells is decreased when the amount of surface vimentin is reduced. Our results provide the first evidence that ECM stiffness can mediate the susceptibility of mammalian host cells to infection by a bacterial pathogen.",2018 Jul 1,"['Bastounis, Effie E.', 'Yeh, Yi-Ting', 'Theriot, Julie A.']",Mol Biol Cell,,,True
ba341ac2252e77be6216073c6ae7af976bb7343a,PMC,Matrix stiffness modulates infection of endothelial cells by Listeria monocytogenes via expression of cell surface vimentin,http://dx.doi.org/10.1091/mbc.E18-04-0228,PMC6080647,29718765,CC BY-NC-SA,"Extracellular matrix stiffness (ECM) is one of the many mechanical forces acting on mammalian adherent cells and an important determinant of cellular function. While the effect of ECM stiffness on many aspects of cellular behavior has been studied previously, how ECM stiffness might mediate susceptibility of host cells to infection by bacterial pathogens is hitherto unexplored. To address this open question, we manufactured hydrogels of varying physiologically relevant stiffness and seeded human microvascular endothelial cells (HMEC-1) on them. We then infected HMEC-1 with the bacterial pathogen Listeria monocytogenes (Lm) and found that adhesion of Lm to host cells increases monotonically with increasing matrix stiffness, an effect that requires the activity of focal adhesion kinase (FAK). We identified cell surface vimentin as a candidate surface receptor mediating stiffness-dependent adhesion of Lm to HMEC-1 and found that bacterial infection of these host cells is decreased when the amount of surface vimentin is reduced. Our results provide the first evidence that ECM stiffness can mediate the susceptibility of mammalian host cells to infection by a bacterial pathogen.",2018 Jul 1,"['Bastounis, Effie E.', 'Yeh, Yi-Ting', 'Theriot, Julie A.']",Mol Biol Cell,,,False
95ec993129c313d381f4065b6391f0fd40bedab5,PMC,In wound repair vimentin mediates the transition of mesenchymal leader cells to a myofibroblast phenotype,http://dx.doi.org/10.1091/mbc.E17-06-0364,PMC6080657,29718762,CC BY-NC-SA,"Following injury, mesenchymal repair cells are activated to function as leader cells that modulate wound healing. These cells have the potential to differentiate to myofibroblasts, resulting in fibrosis and scarring. The signals underlying these differing pathways are complex and incompletely understood. The ex vivo mock cataract surgery cultures are an attractive model with which to address this question. With this model we study, concurrently, the mechanisms that control mesenchymal leader cell function in injury repair within their native microenvironment and the signals that induce this same cell population to acquire a myofibroblast phenotype when these cells encounter the environment of the adjacent tissue culture platform. Here we show that on injury, the cytoskeletal protein vimentin is released into the extracellular space, binds to the cell surface of the mesenchymal leader cells located at the wound edge in the native matrix environment, and supports wound closure. In profibrotic environments, the extracellular vimentin pool also links specifically to the mesenchymal leader cells and has an essential role in signaling their fate change to a myofibroblast. These findings suggest a novel role for extracellular, cell-surface–associated vimentin in mediating repair-cell function in wound repair and in transitioning these cells to a myofibroblast phenotype.",2018 Jul 1,"['Walker, J. L.', 'Bleaken, B. M.', 'Romisher, A. R.', 'Alnwibit, A. A.', 'Menko, A. S.']",Mol Biol Cell,,,True
28f2a06fb16fdc5824d33e0d93c67e0aa1107ecc,PMC,In wound repair vimentin mediates the transition of mesenchymal leader cells to a myofibroblast phenotype,http://dx.doi.org/10.1091/mbc.E17-06-0364,PMC6080657,29718762,CC BY-NC-SA,"Following injury, mesenchymal repair cells are activated to function as leader cells that modulate wound healing. These cells have the potential to differentiate to myofibroblasts, resulting in fibrosis and scarring. The signals underlying these differing pathways are complex and incompletely understood. The ex vivo mock cataract surgery cultures are an attractive model with which to address this question. With this model we study, concurrently, the mechanisms that control mesenchymal leader cell function in injury repair within their native microenvironment and the signals that induce this same cell population to acquire a myofibroblast phenotype when these cells encounter the environment of the adjacent tissue culture platform. Here we show that on injury, the cytoskeletal protein vimentin is released into the extracellular space, binds to the cell surface of the mesenchymal leader cells located at the wound edge in the native matrix environment, and supports wound closure. In profibrotic environments, the extracellular vimentin pool also links specifically to the mesenchymal leader cells and has an essential role in signaling their fate change to a myofibroblast. These findings suggest a novel role for extracellular, cell-surface–associated vimentin in mediating repair-cell function in wound repair and in transitioning these cells to a myofibroblast phenotype.",2018 Jul 1,"['Walker, J. L.', 'Bleaken, B. M.', 'Romisher, A. R.', 'Alnwibit, A. A.', 'Menko, A. S.']",Mol Biol Cell,,,False
b533398000a2ca0d89d244e430d7eb5f3d82fc71,PMC,Cooperativity Enables Non-neutralizing Antibodies to Neutralize Ebolavirus,http://dx.doi.org/10.1016/j.celrep.2017.03.049,PMC6082427,28402862,CC BY-NC-ND,"Drug combinations are synergistic when their combined efficacy exceeds the sum of the individual actions, but they rarely include ineffective drugs that become effective only in combination. We identified several ‘‘enabling pairs’’ of neutralizing and non-neutralizing anti-ebolavirus monoclonal antibodies, whose combination exhibited new functional profiles, including transforming a non-neutralizing antibody to a neutralizer. Sub-neutralizing concentrations of antibodies 2G4 or m8C4 enabled non-neutralizing antibody FVM09 (IC(50) >1 mM) to exhibit potent neutralization (IC(50) 1–10 nM). While FVM09 or m8C4 alone failed to protect Ebola-virus-infected mice, a combination of the two antibodies provided 100% protection. Furthermore, non-neutralizers FVM09 and FVM02 exponentially enhanced the potency of two neu-tralizing antibodies against both Ebola and Sudan viruses. We identified a hotspot for the binding of these enabling antibody pairs near the interface of the glycan cap and GP2. Enabling cooperativity may be an underappreciated phenomenon for viruses, with implications for the design and development of immunotherapeutics and vaccines.",2017 Apr 11,"['Howell, Katie A.', 'Brannan, Jennifer M.', 'Bryan, Christopher', 'McNeal, Andrew', 'Davidson, Edgar', 'Turner, Hannah L.', 'Vu, Hong', 'Shulenin, Sergey', 'He, Shihua', 'Kuehne, Ana', 'Herbert, Andrew S.', 'Qiu, Xiangguo', 'Doranz, Benjamin J.', 'Holtsberg, Frederick W.', 'Ward, Andrew B.', 'Dye, John M.', 'Aman, M. Javad']",Cell Rep,,,True
957546c361623256842c4f840a02b359612c24c1,PMC,Cooperativity Enables Non-neutralizing Antibodies to Neutralize Ebolavirus,http://dx.doi.org/10.1016/j.celrep.2017.03.049,PMC6082427,28402862,CC BY-NC-ND,"Drug combinations are synergistic when their combined efficacy exceeds the sum of the individual actions, but they rarely include ineffective drugs that become effective only in combination. We identified several ‘‘enabling pairs’’ of neutralizing and non-neutralizing anti-ebolavirus monoclonal antibodies, whose combination exhibited new functional profiles, including transforming a non-neutralizing antibody to a neutralizer. Sub-neutralizing concentrations of antibodies 2G4 or m8C4 enabled non-neutralizing antibody FVM09 (IC(50) >1 mM) to exhibit potent neutralization (IC(50) 1–10 nM). While FVM09 or m8C4 alone failed to protect Ebola-virus-infected mice, a combination of the two antibodies provided 100% protection. Furthermore, non-neutralizers FVM09 and FVM02 exponentially enhanced the potency of two neu-tralizing antibodies against both Ebola and Sudan viruses. We identified a hotspot for the binding of these enabling antibody pairs near the interface of the glycan cap and GP2. Enabling cooperativity may be an underappreciated phenomenon for viruses, with implications for the design and development of immunotherapeutics and vaccines.",2017 Apr 11,"['Howell, Katie A.', 'Brannan, Jennifer M.', 'Bryan, Christopher', 'McNeal, Andrew', 'Davidson, Edgar', 'Turner, Hannah L.', 'Vu, Hong', 'Shulenin, Sergey', 'He, Shihua', 'Kuehne, Ana', 'Herbert, Andrew S.', 'Qiu, Xiangguo', 'Doranz, Benjamin J.', 'Holtsberg, Frederick W.', 'Ward, Andrew B.', 'Dye, John M.', 'Aman, M. Javad']",Cell Rep,,,False
1f475d5dbca18aa9710ca227dad58204cc1f21f3,PMC,Cooperativity Enables Non-neutralizing Antibodies to Neutralize Ebolavirus,http://dx.doi.org/10.1016/j.celrep.2017.03.049,PMC6082427,28402862,CC BY-NC-ND,"Drug combinations are synergistic when their combined efficacy exceeds the sum of the individual actions, but they rarely include ineffective drugs that become effective only in combination. We identified several ‘‘enabling pairs’’ of neutralizing and non-neutralizing anti-ebolavirus monoclonal antibodies, whose combination exhibited new functional profiles, including transforming a non-neutralizing antibody to a neutralizer. Sub-neutralizing concentrations of antibodies 2G4 or m8C4 enabled non-neutralizing antibody FVM09 (IC(50) >1 mM) to exhibit potent neutralization (IC(50) 1–10 nM). While FVM09 or m8C4 alone failed to protect Ebola-virus-infected mice, a combination of the two antibodies provided 100% protection. Furthermore, non-neutralizers FVM09 and FVM02 exponentially enhanced the potency of two neu-tralizing antibodies against both Ebola and Sudan viruses. We identified a hotspot for the binding of these enabling antibody pairs near the interface of the glycan cap and GP2. Enabling cooperativity may be an underappreciated phenomenon for viruses, with implications for the design and development of immunotherapeutics and vaccines.",2017 Apr 11,"['Howell, Katie A.', 'Brannan, Jennifer M.', 'Bryan, Christopher', 'McNeal, Andrew', 'Davidson, Edgar', 'Turner, Hannah L.', 'Vu, Hong', 'Shulenin, Sergey', 'He, Shihua', 'Kuehne, Ana', 'Herbert, Andrew S.', 'Qiu, Xiangguo', 'Doranz, Benjamin J.', 'Holtsberg, Frederick W.', 'Ward, Andrew B.', 'Dye, John M.', 'Aman, M. Javad']",Cell Rep,,,True
81b22a5b5989dfc8f57c6d05fd29d3c735785887,PMC,Chimeric camel/human heavy-chain antibodies protect against MERS-CoV infection,http://dx.doi.org/10.1126/sciadv.aas9667,PMC6082650,30101189,CC BY-NC,"Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause outbreaks in humans as a result of spillover events from dromedaries. In contrast to humans, MERS-CoV–exposed dromedaries develop only very mild infections and exceptionally potent virus-neutralizing antibody responses. These strong antibody responses may be caused by affinity maturation as a result of repeated exposure to the virus or by the fact that dromedaries—apart from conventional antibodies—have relatively unique, heavy chain–only antibodies (HCAbs). These HCAbs are devoid of light chains and have long complementarity-determining regions with unique epitope binding properties, allowing them to recognize and bind with high affinity to epitopes not recognized by conventional antibodies. Through direct cloning and expression of the variable heavy chains (VHHs) of HCAbs from the bone marrow of MERS-CoV–infected dromedaries, we identified several MERS-CoV–specific VHHs or nanobodies. In vitro, these VHHs efficiently blocked virus entry at picomolar concentrations. The selected VHHs bind with exceptionally high affinity to the receptor binding domain of the viral spike protein. Furthermore, camel/human chimeric HCAbs—composed of the camel VHH linked to a human Fc domain lacking the CH1 exon—had an extended half-life in the serum and protected mice against a lethal MERS-CoV challenge. HCAbs represent a promising alternative strategy to develop novel interventions not only for MERS-CoV but also for other emerging pathogens.",2018 Aug 8,"['Stalin Raj, V.', 'Okba, Nisreen M. A.', 'Gutierrez-Alvarez, Javier', 'Drabek, Dubravka', 'van Dieren, Brenda', 'Widagdo, W.', 'Lamers, Mart M.', 'Widjaja, Ivy', 'Fernandez-Delgado, Raul', 'Sola, Isabel', 'Bensaid, Albert', 'Koopmans, Marion P.', 'Segalés, Joaquim', 'Osterhaus, Albert D. M. E.', 'Bosch, Berend Jan', 'Enjuanes, Luis', 'Haagmans, Bart L.']",Sci Adv,,,True
48b079bc190854ee0bb9356bb40595ecf1e7288f,PMC,Chimeric camel/human heavy-chain antibodies protect against MERS-CoV infection,http://dx.doi.org/10.1126/sciadv.aas9667,PMC6082650,30101189,CC BY-NC,"Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause outbreaks in humans as a result of spillover events from dromedaries. In contrast to humans, MERS-CoV–exposed dromedaries develop only very mild infections and exceptionally potent virus-neutralizing antibody responses. These strong antibody responses may be caused by affinity maturation as a result of repeated exposure to the virus or by the fact that dromedaries—apart from conventional antibodies—have relatively unique, heavy chain–only antibodies (HCAbs). These HCAbs are devoid of light chains and have long complementarity-determining regions with unique epitope binding properties, allowing them to recognize and bind with high affinity to epitopes not recognized by conventional antibodies. Through direct cloning and expression of the variable heavy chains (VHHs) of HCAbs from the bone marrow of MERS-CoV–infected dromedaries, we identified several MERS-CoV–specific VHHs or nanobodies. In vitro, these VHHs efficiently blocked virus entry at picomolar concentrations. The selected VHHs bind with exceptionally high affinity to the receptor binding domain of the viral spike protein. Furthermore, camel/human chimeric HCAbs—composed of the camel VHH linked to a human Fc domain lacking the CH1 exon—had an extended half-life in the serum and protected mice against a lethal MERS-CoV challenge. HCAbs represent a promising alternative strategy to develop novel interventions not only for MERS-CoV but also for other emerging pathogens.",2018 Aug 8,"['Stalin Raj, V.', 'Okba, Nisreen M. A.', 'Gutierrez-Alvarez, Javier', 'Drabek, Dubravka', 'van Dieren, Brenda', 'Widagdo, W.', 'Lamers, Mart M.', 'Widjaja, Ivy', 'Fernandez-Delgado, Raul', 'Sola, Isabel', 'Bensaid, Albert', 'Koopmans, Marion P.', 'Segalés, Joaquim', 'Osterhaus, Albert D. M. E.', 'Bosch, Berend Jan', 'Enjuanes, Luis', 'Haagmans, Bart L.']",Sci Adv,,,False
f5faed882955e964aa9ea7ac455746bcfec521ba,PMC,Purification and characterization of monoclonal IgG antibodies recognizing Ebola virus glycoprotein,http://dx.doi.org/10.7774/cevr.2018.7.2.119,PMC6082671,30112351,CC BY-NC,"PURPOSE: The goal of this study was to purify and characterize Ebola virus glycoprotein (GP)-specific IgG antibodies from hybridoma clones. MATERIALS AND METHODS: For hybridoma production, mice were injected by intramuscular-electroporation with GP DNA vaccines, and boosted with GP vaccines. The spleen cells were used for producing GP-specific hybridoma. Enzyme-linked immunosorbent assay, Western blot assay, flow cytometry, and virus-neutralizing assay were used to test the ability of monoclonal IgG antibodies to recognize GP and neutralize Ebola virus. RESULTS: Twelve hybridomas, the cell supernatants of which displayed GP-binding activity by enzyme-linked immunosorbent assay and the presence of both IgG heavy and light chains by Western blot assay, were chosen as a possible IgG producer. Among these, five clones (C36-1, D11-3, D12-1, D34-2, and E140-2) were identified to secrete monoclonal IgG antibodies. When the monoclonal IgG antibodies from the 5 clones were tested for their antigen specificity, they recognized GP in an antigen-specific and IgG dose-dependent manner. They remained reactive to GP at the lowest tested concentrations (1.953–7.8 ng/mL). In particular, IgG antibodies from clones D11-3, D12-1, and E140-2 recognized the native forms of GP expressed on the cell surface. These antibodies were identified as IgG1, IgG2a, or IgG2b kappa types and appeared to recognize the native forms of GP, but not the denatured forms of GP, as determined by Western blot assay. Despite their GP-binding activity, none of the IgG antibodies neutralized Ebola virus infection in vitro, suggesting that these antibodies are unable to neutralize Ebola virus infection. CONCLUSION: This study shows that the purified IgG antibodies from 5 clones (C36-1, D11-3, D12-1, D34-2, and E140-2) possess GP-binding activity but not Ebola virus-neutralizing activity.",2018 Jul 31,"['Han, Baek-Sang', 'Jang, Ho-Young', 'Racine, Trina', 'Qiu, Xiangguo', 'Sin, Jeong-Im']",Clin Exp Vaccine Res,,,True
95932152552726907534123bae9e9c61eec15d02,PMC,Long-Term Culture of Distal Airway Epithelial Cells Allows Differentiation Towards Alveolar Epithelial Cells Suited for Influenza Virus Studies,http://dx.doi.org/10.1016/j.ebiom.2018.05.032,PMC6085545,29937069,CC BY-NC-ND,"As the target organ for numerous pathogens, the lung epithelium exerts critical functions in health and disease. However, research in this area has been hampered by the quiescence of the alveolar epithelium under standard culture conditions. Here, we used human distal airway epithelial cells (DAECs) to generate alveolar epithelial cells. Long-term, robust growth of human DAECs was achieved using co-culture with feeder cells and supplementation with epidermal growth factor (EGF), Rho-associated protein kinase inhibitor Y27632, and the Notch pathway inhibitor dibenzazepine (DBZ). Removal of feeders and priming with DBZ and a cocktail of lung maturation factors prevented the spontaneous differentiation into airway club cells and instead induced differentiation to alveolar epithelial cells. We successfully transferred this approach to chicken distal airway cells, thus generating a zoonotic infection model that enables studies on influenza A virus replication. These cells are also amenable for gene knockdown using RNAi technology, indicating the suitability of the model for mechanistic studies into lung function and disease.",2018 Jun 22,"['Imai-Matsushima, Aki', 'Martin-Sancho, Laura', 'Karlas, Alexander', 'Imai, Seiichiro', 'Zoranovic, Tamara', 'Hocke, Andreas C.', 'Mollenkopf, Hans-Joachim', 'Berger, Hilmar', 'Meyer, Thomas F.']",EBioMedicine,,,False
5714aa6e21c68e654dc154e682ee07b25100472f,PMC,Long-Term Culture of Distal Airway Epithelial Cells Allows Differentiation Towards Alveolar Epithelial Cells Suited for Influenza Virus Studies,http://dx.doi.org/10.1016/j.ebiom.2018.05.032,PMC6085545,29937069,CC BY-NC-ND,"As the target organ for numerous pathogens, the lung epithelium exerts critical functions in health and disease. However, research in this area has been hampered by the quiescence of the alveolar epithelium under standard culture conditions. Here, we used human distal airway epithelial cells (DAECs) to generate alveolar epithelial cells. Long-term, robust growth of human DAECs was achieved using co-culture with feeder cells and supplementation with epidermal growth factor (EGF), Rho-associated protein kinase inhibitor Y27632, and the Notch pathway inhibitor dibenzazepine (DBZ). Removal of feeders and priming with DBZ and a cocktail of lung maturation factors prevented the spontaneous differentiation into airway club cells and instead induced differentiation to alveolar epithelial cells. We successfully transferred this approach to chicken distal airway cells, thus generating a zoonotic infection model that enables studies on influenza A virus replication. These cells are also amenable for gene knockdown using RNAi technology, indicating the suitability of the model for mechanistic studies into lung function and disease.",2018 Jun 22,"['Imai-Matsushima, Aki', 'Martin-Sancho, Laura', 'Karlas, Alexander', 'Imai, Seiichiro', 'Zoranovic, Tamara', 'Hocke, Andreas C.', 'Mollenkopf, Hans-Joachim', 'Berger, Hilmar', 'Meyer, Thomas F.']",EBioMedicine,,,False
80cdffc26a496e89e2d94c7478749adbabafe180,PMC,"A provincial Acute Febrile Illness Surveillance Network (GAFINet), South Korea",http://dx.doi.org/10.5210/ojphi.v10i1.8655,PMC6087987,,CC BY-NC,,2018 May 30,"['Sung, Yeon-Hee', 'Yi, Seon-Ju', 'Song, Kyoung-Ho', 'Kim, Yang Lee', 'Kim, Jeong Yeon', 'Kim, Jieun', 'Kim, Hong Bin', 'Kim, Eu Suk', 'Lee, Heeyoung', 'Jo, Soo-nam', None, 'Kim, Na-young', 'Park, Eun-jung', 'Lee, Yu-ra', 'Jeong, Hye-jin', 'Choi, Sungyong', 'Choi, Won Suk']",Online J Public Health Inform,,,True
ac3dcfecd7f5486d24470895e9248688b812af9e,PMC,Forecasting Emergency Department Admissions for Pneumonia in Tropical Singapore,http://dx.doi.org/10.5210/ojphi.v10i1.8327,PMC6087989,,CC BY-NC,,2018 May 30,"['Lim, Cindy', 'Chen, Mark']",Online J Public Health Inform,,,False
7be16a5fe61f446de54e71a73b7686d629f24059,PMC,"Viral causes of Influenza Like Illness in Uganda, 2008 to 2017.",http://dx.doi.org/10.5210/ojphi.v10i1.8990,PMC6088015,,CC BY-NC,,2018 May 30,"['Mimbe, Derrick E.', 'Byarugaba, Denis K.', 'Erima, Bernard', 'Mworozi, Edison', 'Millard, Monica', 'Tugume, Titus', 'Kiconco, Jocelyn', 'Lamunu, Paska', 'Kibuuka, Hannah', 'Wabwire-Mangen, Fred']",Online J Public Health Inform,,,True
6c7341f17bfd790cdc05b6d1010c63f4f8eb5890,PMC,Antivirals for influenza-Like Illness? A randomised Controlled trial of Clinical and Cost effectiveness in primary CarE (ALIC(4) E): the ALIC(4) E protocol,http://dx.doi.org/10.1136/bmjopen-2017-021032,PMC6089276,30002007,CC BY-NC,"INTRODUCTION: Effective management of seasonal and pandemic influenza is a high priority internationally. Guidelines in many countries recommend antiviral treatment for older people and individuals with comorbidity at increased risk of complications. However, antivirals are not often prescribed in primary care in Europe, partly because its clinical and cost effectiveness has been insufficiently demonstrated by non-industry funded and pragmatic studies. METHODS AND ANALYSIS: Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE is a European multinational, multicentre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial. Initial trial arms will be best usual primary care and best usual primary care plus treatment with oseltamivir for 5 days. We aim to recruit at least 2500 participants ≥1 year presenting with influenza-like illness (ILI), with symptom duration ≤72 hours in primary care over three consecutive periods of confirmed high influenza incidence. Participant outcomes will be followed up to 28 days by diary and telephone. The primary objective is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity with fever, headache and muscle ache reduced to minor severity or less. Secondary objectives include estimating cost-effectiveness, benefits in subgroups according to age (<12, 12–64 and >64 years), severity of symptoms at presentation (low, medium and high), comorbidity (yes/no), duration of symptoms (≤48 hours/>48–72 hours), complications (hospital admission and pneumonia), use of additional prescribed medication including antibiotics, use of over-the-counter medicines and self-management of ILI symptoms. ETHICS AND DISSEMINATION: Research ethics committee (REC) approval was granted by the NRES Committee South Central (Oxford B) and Clinical Trial Authority (CTA) approval by The Medicines and Healthcare products Regulatory Agency. All participating countries gained national REC and CTA approval as required. Dissemination of results will be through peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN27908921; Pre-results.",2018 Jul 12,"['Bongard, Emily', 'van der Velden, Alike W', 'Cook, Johanna', 'Saville, Ben', 'Beutels, Philippe', 'Munck Aabenhus, Rune', 'Brugman, Curt', 'Chlabicz, Slawomir', 'Coenen, Samuel', 'Colliers, Annelies', 'Davies, Melanie', 'De Paor, Muireann', 'De Sutter, An', 'Francis, Nick A', 'Glinz, Dominik', 'Godycki-ćwirko, Maciek', 'Goossens, Herman', 'Holmes, Jane', 'Ieven, Margareta', 'de Jong, Menno', 'Lindbaek, Morten', 'Little, Paul', 'Martinón-Torres, Frederico', 'Moragas, Ana', 'Pauer, József', 'Pfeiferová, Markéta', 'Radzeviciene-Jurgute, Ruta', 'Sundvall, Pär-Daniel', 'Torres, Antoni', 'Touboul, Pia', 'Varthalis, Dionyssios', 'Verheij, Theo', 'Butler, Christopher C']",BMJ Open,,,True
480e5240848f603d3c04a1e21cecfe502a13cd89,PMC,Antivirals for influenza-Like Illness? A randomised Controlled trial of Clinical and Cost effectiveness in primary CarE (ALIC(4) E): the ALIC(4) E protocol,http://dx.doi.org/10.1136/bmjopen-2017-021032,PMC6089276,30002007,CC BY-NC,"INTRODUCTION: Effective management of seasonal and pandemic influenza is a high priority internationally. Guidelines in many countries recommend antiviral treatment for older people and individuals with comorbidity at increased risk of complications. However, antivirals are not often prescribed in primary care in Europe, partly because its clinical and cost effectiveness has been insufficiently demonstrated by non-industry funded and pragmatic studies. METHODS AND ANALYSIS: Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE is a European multinational, multicentre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial. Initial trial arms will be best usual primary care and best usual primary care plus treatment with oseltamivir for 5 days. We aim to recruit at least 2500 participants ≥1 year presenting with influenza-like illness (ILI), with symptom duration ≤72 hours in primary care over three consecutive periods of confirmed high influenza incidence. Participant outcomes will be followed up to 28 days by diary and telephone. The primary objective is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity with fever, headache and muscle ache reduced to minor severity or less. Secondary objectives include estimating cost-effectiveness, benefits in subgroups according to age (<12, 12–64 and >64 years), severity of symptoms at presentation (low, medium and high), comorbidity (yes/no), duration of symptoms (≤48 hours/>48–72 hours), complications (hospital admission and pneumonia), use of additional prescribed medication including antibiotics, use of over-the-counter medicines and self-management of ILI symptoms. ETHICS AND DISSEMINATION: Research ethics committee (REC) approval was granted by the NRES Committee South Central (Oxford B) and Clinical Trial Authority (CTA) approval by The Medicines and Healthcare products Regulatory Agency. All participating countries gained national REC and CTA approval as required. Dissemination of results will be through peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN27908921; Pre-results.",2018 Jul 12,"['Bongard, Emily', 'van der Velden, Alike W', 'Cook, Johanna', 'Saville, Ben', 'Beutels, Philippe', 'Munck Aabenhus, Rune', 'Brugman, Curt', 'Chlabicz, Slawomir', 'Coenen, Samuel', 'Colliers, Annelies', 'Davies, Melanie', 'De Paor, Muireann', 'De Sutter, An', 'Francis, Nick A', 'Glinz, Dominik', 'Godycki-ćwirko, Maciek', 'Goossens, Herman', 'Holmes, Jane', 'Ieven, Margareta', 'de Jong, Menno', 'Lindbaek, Morten', 'Little, Paul', 'Martinón-Torres, Frederico', 'Moragas, Ana', 'Pauer, József', 'Pfeiferová, Markéta', 'Radzeviciene-Jurgute, Ruta', 'Sundvall, Pär-Daniel', 'Torres, Antoni', 'Touboul, Pia', 'Varthalis, Dionyssios', 'Verheij, Theo', 'Butler, Christopher C']",BMJ Open,,,True
0d9c772336146ec59aac5659f00313e1a63f8fe6,PMC,Antivirals for influenza-Like Illness? A randomised Controlled trial of Clinical and Cost effectiveness in primary CarE (ALIC(4) E): the ALIC(4) E protocol,http://dx.doi.org/10.1136/bmjopen-2017-021032,PMC6089276,30002007,CC BY-NC,"INTRODUCTION: Effective management of seasonal and pandemic influenza is a high priority internationally. Guidelines in many countries recommend antiviral treatment for older people and individuals with comorbidity at increased risk of complications. However, antivirals are not often prescribed in primary care in Europe, partly because its clinical and cost effectiveness has been insufficiently demonstrated by non-industry funded and pragmatic studies. METHODS AND ANALYSIS: Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE is a European multinational, multicentre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial. Initial trial arms will be best usual primary care and best usual primary care plus treatment with oseltamivir for 5 days. We aim to recruit at least 2500 participants ≥1 year presenting with influenza-like illness (ILI), with symptom duration ≤72 hours in primary care over three consecutive periods of confirmed high influenza incidence. Participant outcomes will be followed up to 28 days by diary and telephone. The primary objective is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity with fever, headache and muscle ache reduced to minor severity or less. Secondary objectives include estimating cost-effectiveness, benefits in subgroups according to age (<12, 12–64 and >64 years), severity of symptoms at presentation (low, medium and high), comorbidity (yes/no), duration of symptoms (≤48 hours/>48–72 hours), complications (hospital admission and pneumonia), use of additional prescribed medication including antibiotics, use of over-the-counter medicines and self-management of ILI symptoms. ETHICS AND DISSEMINATION: Research ethics committee (REC) approval was granted by the NRES Committee South Central (Oxford B) and Clinical Trial Authority (CTA) approval by The Medicines and Healthcare products Regulatory Agency. All participating countries gained national REC and CTA approval as required. Dissemination of results will be through peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN27908921; Pre-results.",2018 Jul 12,"['Bongard, Emily', 'van der Velden, Alike W', 'Cook, Johanna', 'Saville, Ben', 'Beutels, Philippe', 'Munck Aabenhus, Rune', 'Brugman, Curt', 'Chlabicz, Slawomir', 'Coenen, Samuel', 'Colliers, Annelies', 'Davies, Melanie', 'De Paor, Muireann', 'De Sutter, An', 'Francis, Nick A', 'Glinz, Dominik', 'Godycki-ćwirko, Maciek', 'Goossens, Herman', 'Holmes, Jane', 'Ieven, Margareta', 'de Jong, Menno', 'Lindbaek, Morten', 'Little, Paul', 'Martinón-Torres, Frederico', 'Moragas, Ana', 'Pauer, József', 'Pfeiferová, Markéta', 'Radzeviciene-Jurgute, Ruta', 'Sundvall, Pär-Daniel', 'Torres, Antoni', 'Touboul, Pia', 'Varthalis, Dionyssios', 'Verheij, Theo', 'Butler, Christopher C']",BMJ Open,,,False
b0d6f7e423d86c57973ae2ca6cbfff3a9acecc0a,PMC,Coronavirus and Chronic Lung Allograft Dysfunction: Hiding in Plain Sight?,http://dx.doi.org/10.1097/TXD.0000000000000809,PMC6092178,30255131,CC BY-NC-ND,,2018 Jul 11,"['Mitchell, Alicia B.', 'Glanville, Allan R.']",Transplant Direct,,,True
b7ab9571dc69783d3b84dc3c5a24656db182afb6,PMC,Viral Respiratory Tract Infection During the First Postoperative Year Is a Risk Factor for Chronic Rejection After Lung Transplantation,http://dx.doi.org/10.1097/TXD.0000000000000808,PMC6092179,30255130,CC BY-NC-ND,"BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the major limiting factor for long-term survival in lung transplant recipients. Viral respiratory tract infection (VRTI) has been previously associated with CLAD development. The main purpose of this study was to evaluate the long-term effects of VRTI during the first year after lung transplantation in relation to CLAD development. METHOD: Ninety-eight patients undergoing lung transplantation were prospectively enrolled between 2009 and 2012. They were monitored for infections with predefined intervals and on extra visits during the first year, the total follow-up period ranged between 5 and 8 years. Nasopharyngeal swab and bronchoalveolar lavage samples were analyzed using a multiplex polymerase chain reaction panel for respiratory pathogens. Data regarding clinical characteristics and infectious events were recorded. RESULTS: Viral respiratory tract infection during the first year was identified as a risk factor for long-term CLAD development (P = 0.041, hazard ratio 1.94 [1.03-3.66]) in a time-dependent multivariate Cox regression analysis. We also found that coronavirus in particular was associated with increased risk for CLAD development. Other identified risk factors were acute rejection and cyclosporine treatment. CONCLUSIONS: This study suggests that VRTI during the first year after lung transplantation is associated with long-term CLAD development and that coronavirus infections in particular might be a risk factor.",2018 Jul 11,"['Magnusson, Jesper', 'Westin, Johan', 'Andersson, Lars-Magnus', 'Lindh, Magnus', 'Brittain-Long, Robin', 'Nordén, Rickard', 'Riise, Gerdt C.']",Transplant Direct,,,True
45e84ec766785509223abd5e681917cb95f135b4,PMC,Viral Respiratory Tract Infection During the First Postoperative Year Is a Risk Factor for Chronic Rejection After Lung Transplantation,http://dx.doi.org/10.1097/TXD.0000000000000808,PMC6092179,30255130,CC BY-NC-ND,"BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the major limiting factor for long-term survival in lung transplant recipients. Viral respiratory tract infection (VRTI) has been previously associated with CLAD development. The main purpose of this study was to evaluate the long-term effects of VRTI during the first year after lung transplantation in relation to CLAD development. METHOD: Ninety-eight patients undergoing lung transplantation were prospectively enrolled between 2009 and 2012. They were monitored for infections with predefined intervals and on extra visits during the first year, the total follow-up period ranged between 5 and 8 years. Nasopharyngeal swab and bronchoalveolar lavage samples were analyzed using a multiplex polymerase chain reaction panel for respiratory pathogens. Data regarding clinical characteristics and infectious events were recorded. RESULTS: Viral respiratory tract infection during the first year was identified as a risk factor for long-term CLAD development (P = 0.041, hazard ratio 1.94 [1.03-3.66]) in a time-dependent multivariate Cox regression analysis. We also found that coronavirus in particular was associated with increased risk for CLAD development. Other identified risk factors were acute rejection and cyclosporine treatment. CONCLUSIONS: This study suggests that VRTI during the first year after lung transplantation is associated with long-term CLAD development and that coronavirus infections in particular might be a risk factor.",2018 Jul 11,"['Magnusson, Jesper', 'Westin, Johan', 'Andersson, Lars-Magnus', 'Lindh, Magnus', 'Brittain-Long, Robin', 'Nordén, Rickard', 'Riise, Gerdt C.']",Transplant Direct,,,False
488e866a3ed2d3764a91dad6a668a304859ce1ad,PMC,Viral lncRNA: A regulatory molecule for controlling virus life cycle,http://dx.doi.org/10.1016/j.ncrna.2017.03.002,PMC6096409,30159419,CC BY-NC-ND,"Long non-coding RNAs (lncRNAs) are found not only in mammals but also in other organisms, including viruses. Recent findings suggest that lncRNAs play various regulatory roles in multiple major biological and pathological processes. During viral life cycles, lncRNAs are involved in a series of steps, including enhancing viral gene expression, promoting viral replication and genome packaging, boosting virion release, maintaining viral latency and assisting viral transformation; additionally, lncRNAs antagonize host antiviral innate immune responses. In contrast to proteins that function in viral infection, lncRNAs are expected to be novel targets for the modulation of all types of biochemical processes due to their broad characteristics and profound influence. This review highlights our current understanding of the regulatory roles of lncRNAs during viral infection processes with an emphasis on the potential usefulness of lncRNAs as a target for viral intervention strategies, which could have therapeutic implications for the application of a clinical approach for the treatment of viral diseases.",2017 Mar 23,"['Wang, Ziqiang', 'Zhao, Yiwan', 'Zhang, Yaou']",Noncoding RNA Res,,,False
34dbc74805291ff544a0944fd54d1e4f1a470080,PMC,Current research for a vaccine against Lassa hemorrhagic fever virus,http://dx.doi.org/10.2147/DDDT.S147276,PMC6097522,30147299,CC BY-NC,"Lassa virus (LASV) is a rodent-borne arenavirus endemic to several West African countries that causes Lassa fever (LF). LF is typically mild but it can cause severe disease characterized by hemorrhagic fever and multi-organ failure. A current outbreak of LASV in Nigeria has seen greater than 300 cases with a case fatality rate of 22%. Currently, there are limited treatment options and no vaccine candidates are approved to prevent LASV infection. The Coalition for Epidemic Preparedness Innovations has identified LASV as an emerging pathogen of high consequence and this has resulted in a push for several preclinical vaccine candidates to be advanced toward clinical trials. Here, we discuss several important aspects of LASV infection including immunobiology, immune evasion, and correlates of protection against LF, which have been identified through animal models and human infections. In addition, we discuss several vaccine candidates that have shown efficacy in animal models that could be advanced toward clinical trials. The increased fatality rate seen in the recent LASV outbreak in Nigeria highlights the importance of developing effective treatment and prevention strategies against LF. The spike in LASV cases seen in West Africa has the potential for increased mortality and human-to-human transmission, making the development and testing of effective vaccines for LASV critical.",2018 Aug 14,"['Warner, Bryce M', 'Safronetz, David', 'Stein, Derek R']",Drug Des Devel Ther,,,True
a633596dc4ee28692afaa88122c65b997d1e4d1f,PMC,Potential and challenges of tannins as an alternative to in-feed antibiotics for farm animal production,http://dx.doi.org/10.1016/j.aninu.2017.09.004,PMC6104569,30140753,CC BY-NC-ND,"Naturally occurring plant compounds including tannins, saponins and essential oils are extensively assessed as natural alternatives to in-feed antibiotics. Tannins are a group of polyphenolic compounds that are widely present in plant region and possess various biological activities including antimicrobial, anti-parasitic, anti-viral, antioxidant, anti-inflammatory, immunomodulation, etc. Therefore, tannins are the major research subject in developing natural alternative to in-feed antibiotics. Strong protein affinity is the well-recognized property of plant tannins, which has successfully been applied to ruminant nutrition to decrease protein degradation in the rumen, and thereby improve protein utilization and animal production efficiency. Incorporations of tannin-containing forage in ruminant diets to control animal pasture bloat, intestinal parasite and pathogenic bacteria load are another 3 important applications of tannins in ruminant animals. Tannins have traditionally been regarded as “anti-nutritional factor” for monogastric animals and poultry, but recent researches have revealed some of them, when applied in appropriate manner, improved intestinal microbial ecosystem, enhanced gut health and hence increased productive performance. The applicability of plant tannins as an alternative to in-feed antibiotics depends on many factors that contribute to the great variability in their observed efficacies.",2018 Jun 14,"['Huang, Qianqian', 'Liu, Xiuli', 'Zhao, Guoqi', 'Hu, Tianming', 'Wang, Yuxi']",Anim Nutr,,,False
0e18097a83b2801c4865c72065b7933fa24face3,PMC,"Nonproliferative and Proliferative Lesions of the Ratand Mouse Special Sense Organs(Ocular [eye and glands], Olfactory and Otic)",http://dx.doi.org/10.1293/tox.31.97S,PMC6108092,30158741,CC BY-NC-ND,,2018 Jul 28,"['Ramos, Meg Ferrell', 'Baker, Julia', 'Atzpodien, Elke-Astrid', 'Bach, Ute', 'Brassard, Jacqueline', 'Cartwright, James', 'Farman, Cynthia', 'Fishman, Cindy', 'Jacobsen, Matt', 'Junker-Walker, Ursula', 'Kuper, Frieke', 'Moreno, Maria Cecilia Rey', 'Rittinghausen, Susanne', 'Schafer, Ken', 'Tanaka, Kohji', 'Teixeira, Leandro', 'Yoshizawa, Katsuhiko', 'Zhang, Hui']",J Toxicol Pathol,,,True
4d186611ecffce20666431e3e9988308833c0236,PMC,The prophylactic effect of different levels of positive endexpiratory pressure on the incidence rate of atelectasis after cardiac surgery: A Randomized Controlled Trial,http://dx.doi.org/10.14196/mjiri.32.20,PMC6108254,30159271,CC BY-NC,"Background: The use of positive end-expiratory pressure (PEEP) can have an important role as one of the ways to prevent and treat atelectasis, but it seems that there is still no consensus about its beneficial level. The aim of this study was to determine the effect of different levels of PEEP on the incidence of atelectasis after heart surgery. Methods: This is a double-blind randomized controlled trial that was adopted from a research project recorded in the Iranian Registry of Clinical Trials. This paper is the result of a research project undertaken at Fatemeh Zahra Hospital (Mazandaran Heart Center) in 2015. 180 patients underwent open heart surgery were selected and were divided randomly into three groups: control, PEEP=8, and PEEP=10 (60 in each group). The patients in the two PEEP8 and PEEP10 intervention groups separately received 8 cm H2O and 10 cm H2O PEEP, respectively, 30 minutes after admission to the ICU for 4 hours and then received 5 cm H2O PEEP until extubation. Atelectasis was examined two hours after the extubation and on the third day after surgery. Results: The incidence rates of atelectasis two hours after extubation on the first day of surgery were 22 (36.7%), 20 (33.3%) and 10 (16.7%) patients in the control, PEEP8 and PEEP10 groups, respectively. The differences were statistically significant among the three groups (p=0.035). The incidence rates of atelectasis on the third day after surgery were 39 (65%), 36 (60%) and 21 (35%) patients in the control, PEEP8 and PEEP10 groups, respectively. The differences were also statistically significant among the three groups (p=0.003). Conclusion: The use of 10 cm H2O PEEP can lead to a reduction in the incidence of atelectasis, intubation time at the ICU and length of ICU and hospital stay. Given that this level of PEEP is effective, this method is recommended to be used in postoperative care of patients.",2018 Mar 10,"['Setak-Berenjestanaki, Mostafa', 'Bagheri-Nesami, Masoumeh', 'Gholipour Baradari, Afshin', 'Mousavinasab, Seyed Nouraddin', 'Ghaffari, Rahman', 'Darbeheshti, Manijeh']",Med J Islam Repub Iran,,,True
0612bb6d157e8cd266943d84daf110c46a56aa23,PMC,Validation of the Munich ChronoType Questionnaire in Korean Older Adults(*),http://dx.doi.org/10.30773/pi.2018.04.09,PMC6111220,30048583,CC BY-NC,"OBJECTIVE: This study aimed to evaluate psychometric properties of the Munich ChronoType Questionnaire (MCTQ) in a sample of Korean older adults. METHODS: One-hundred ninety two participants aged 65 and over completed interview-based questionnaires about chronotype, insomnia, depression, and anxiety. Additionally, a small subset of subjects completed a 7-day sleep diary and actigraphy measurements. RESULTS: Morningness-Eveningness Questionnaire (MEQ) scores were significantly negatively correlated with Midpoint of sleep on free days corrected for sleep debt accumulated through weekdays (MSFsc) (r=-0.45, p<0.01) assessed by the MCTQ. MSFsc using the MCTQ was significantly positively correlated with MSFsc assessed by both the sleep diary (r=0.74, p<0.05) and actigraphy (r=0.76, p<0.05). Additionally, MSFsc assessed by the MCTQ was significantly positively correlated with insomnia (r=0.26, p<0.01), depression (r=0.25, p<0.01), and anxiety (r=0.18, p<0.05). Finally, based on MEQ scores, we derived a cut-off score for the MCTQ that distinguishes morning type and other types (intermediate/evening types) in older adults. CONCLUSION: The results of these studies supported the validity of the MCTQ in Korean older adults. Additionally, while sleep rhythms in elder adults may be more advanced, eveningness tendency may be still important and indicative of sleep and psychological disturbance.",2018 Aug 26,"['Ryu, Hyera', 'Joo, Eun Yeon', 'Choi, Su Jung', 'Suh, Sooyeon']",Psychiatry Investig,,,True
7910f7d2d13423c6eecb4ac66c0349e7830a57aa,PMC,Emodin induces apoptosis in human hepatocellular carcinoma HepaRG cells via the mitochondrial caspase-dependent pathway,http://dx.doi.org/10.3892/or.2018.6620,PMC6111625,30106438,CC BY-NC-ND,"Emodin-induced hepatotoxicity in vivo and in vitro has been gaining increasing attention. However, the exact molecular pathways underlying these effects remain poorly clarified. The aim of the present study was to evaluate the cytotoxic effect of emodin on HepaRG cells and to define the underlying mechanism. The results demonstrated that emodin evidently inhibited HepaRG cell growth in a dose- and time-dependent manner by blocking cell cycle progression in the S and G2/M phase and by inducing apoptosis. Emodin treatment also resulted in generation of reactive oxygen species (ROS), which abrogated mitochondrial membrane potential (MMP). The above effects were all suppressed by antioxidants, such as N-acetylcysteine (NAC). Further studies by western blot analysis howed that emodin upregulated p53, p21, Bax, cyclin E, cleaved caspase-3, 8 and 9, and cleaved poly(ADP-ribose)polymerase (PARP). However, the protein expression of Bcl-2, cyclin A and CDK2 was downregulated. Taken together, our results suggest that emodin induces apoptosis via the mitochondrial apoptosis pathway through cell cycle arrest and ROS generation in HepaRG cells.",2018 Oct 2,"['Dong, Xiaoxv', 'Ni, Boran', 'Fu, Jing', 'Yin, Xingbin', 'You, Longtai', 'Leng, Xin', 'Liang, Xiao', 'Ni, Jian']",Oncol Rep,,,True
5f88b4180ba190e37e27776b11432d61770529ef,PMC,Artificial Intelligence in Public Health and Epidemiology,http://dx.doi.org/10.1055/s-0038-1667082,PMC6115208,30157525,CC BY-NC-ND,"Objectives:  To introduce and summarize current research in the field of Public Health and Epidemiology Informatics. Methods:  The 2017 literature concerning public health and epidemiology informatics was searched in PubMed and Web of Science, and the returned references were reviewed by the two section editors to select 14 candidate best papers. These papers were then peer-reviewed by external reviewers to provide the editorial team with an enlightened vision to select the best papers. Results:  Among the 843 references retrieved from PubMed and Web of Science, two were finally selected as best papers. The first one analyzes the relationship between the disease, social/mass media, and public emotions to understand public overreaction (leading to a noticeable reduction of social and economic activities) in the context of a nation-wide outbreak of Middle East Respiratory Syndrome (MERS) in Korea in 2015. The second paper concerns a new methodology to de-identify patient notes in electronic health records based on artificial neural networks that outperformed existing methods. Conclusions:  Surveillance is still a productive topic in public health informatics but other very important topics in Public Health are appearing. For example, the use of artificial intelligence approaches is increasing.",2018 Aug 29,"['Thiébaut, Rodolphe', 'Thiessard, Frantz', None]",Yearb Med Inform,,,True
9794fdd25bf5ce08230e7f62838876ca45d05b87,PMC,Burden of influenza-related severe acute respiratory infections during Hajj season 1438 (2017). Lessons and future directions,http://dx.doi.org/10.15537/smj.2018.5.21801,PMC6118186,29738015,CC BY-NC-SA,,2018 May,"['Assiri, Abdullah M.', 'Asiri, Sari I.', 'Banassir, Talib', 'Baljoon, Mustafa J.', 'Jokhdar, Hani']",Saudi Med J,,,True
6bd2dac1db0e974c27b6b7b5a17aaab35fc8d36c,PMC,Elevated serum LAMC2 is associated with lymph node metastasis and predicts poor prognosis in penile squamous cell carcinoma,http://dx.doi.org/10.2147/CMAR.S171912,PMC6118283,30214293,CC BY-NC,"PURPOSE: Molecular biomarkers, especially serologic factors, have been widely applied in cancer diagnosis and patient follow-up. However, there are few valuable prognostic factors in penile squamous cell carcinoma (PSCC). Here, the authors investigated whether laminin gamma 2 (LAMC2) expression, especially serum LAMC2 (sLAMC2) level, was a suitable prognostic factor that could aid in the prediction of survival in PSCC. PATIENTS AND METHODS: This study included 114 PSCC patients. Reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect LAMC2 expression; enzyme-linked immunosorbent assays were used to test sLAMC2 concentration; and a Transwell assay and an in vivo experiment in nude mice were used to test PSCC cell migration, invasion, and metastasis. The chi-squared test was used to analyze the association between LAMC2 level and clinical parameters, the Cox proportional hazards regression model was used to evaluate the hazard ratio for death, and Kaplan–Meier analysis with a log-rank test was used for the survival analysis. RESULTS: LAMC2 was overexpressed in PSCC tissues, and the LAMC2 expression level was higher in metastatic lymph node (LN) tissues than in primary cancer tissues; moreover, the LAMC2 levels in primary cancer tissues and sLAMC2 were higher in patients with LN metastasis than in those without LN metastasis. Upregulated LAMC2 facilitated the migration, invasion, and epithelial-to-mesenchymal transition of PSCC cells in vitro and promoted LN metastasis of PSCC cells in nude mice. Elevated LAMC2 levels were strongly correlated with advanced clinicopathologic parameters, especially LN metastasis, in PSCC patients and predicted shorter disease-specific survival. The predictive value of sLAMC2 is superior to that of C-reactive protein and squamous cell carcinoma antigen previously reported in PSCC patients, and a stratification analysis revealed that the level of sLAMC2 had a higher predictive value for disease-specific survival in early penile cancer (especially at the N(0/X) stage) than in later-stage penile cancer. CONCLUSION: These findings suggest that sLAMC2 is a potential serologic prognostic marker in PSCC and could aid in risk stratification in early-stage PSCC patients.",2018 Aug 28,"['Zhou, Qiang-Hua', 'Deng, Chuang-Zhong', 'Chen, Jie-Ping', 'Huang, Kang-Bo', 'Liu, Ting-Yu', 'Yao, Kai', 'Liu, Zhuo-Wei', 'Qin, Zi-Ke', 'Li, Yong-Hong', 'Guo, Sheng-Jie', 'Ye, Yun-Lin', 'Zhou, Fang-Jian', 'Huang, Wenlin', 'Liu, Ran-Yi', 'Han, Hui']",Cancer Manag Res,,,True
e525b075d170cf15ddaf7f9b11f9de5f8ecaaf45,PMC,Chiral zirconium quantum dots: A new class of nanocrystals for optical detection of coronavirus,http://dx.doi.org/10.1016/j.heliyon.2018.e00766,PMC6120744,30186985,CC BY-NC-ND,"A synthetic way of chiral zirconium quantum dots (Zr QDs) was presented for the first time using L(+)-ascorbic acid acts as a surface as well as chiral ligands. Different spectroscopic and microscopic analysis was performed for thorough characterization of Zr QDs. As-synthesized QDs exhibited fluorescence and circular dichroism properties, and the peaks were located at 412 nm and 352 nm, respectively. MTT assay was performed to test the cytotoxicity of the synthesized Zr QDs against rat brain glioma C6 cells. Synthesized QDs was further conjugated with anti-infectious bronchitis virus (IBV) antibodies of coronavirus to form an immunolink at the presence of the target analyte and anti-IBV antibody-conjugated magneto-plasmonic nanoparticles (MPNPs). The fluorescence properties of immuno-conjugated QD–MP NPs nanohybrids through separation by an external magnetic field enabled biosensing of coronavirus with a limit of detection of 79.15 EID/50 μL.",2018 Aug 31,"['Ahmed, Syed Rahin', 'Kang, Seon Woo', 'Oh, Sangjin', 'Lee, Jaebeom', 'Neethirajan, Suresh']",Heliyon,,,False
b38c12ccd389c27706fcf2a50c2274352539fbc3,PMC,Incorporating uracil and 5-halouracils into short peptide nucleic acids for enhanced recognition of A–U pairs in dsRNAs,http://dx.doi.org/10.1093/nar/gky631,PMC6125629,30011039,CC BY-NC,"Double-stranded RNA (dsRNA) structures form triplexes and RNA-protein complexes through binding to single-stranded RNA (ssRNA) regions and proteins, respectively, for diverse biological functions. Hence, targeting dsRNAs through major-groove triplex formation is a promising strategy for the development of chemical probes and potential therapeutics. Short (e.g., 6–10 mer) chemically-modified Peptide Nucleic Acids (PNAs) have been developed that bind to dsRNAs sequence specifically at physiological conditions. For example, a PNA incorporating a modified base thio-pseudoisocytosine (L) has an enhanced recognition of a G–C pair in an RNA duplex through major-groove L·G–C base triple formation at physiological pH, with reduced pH dependence as observed for C(+)·G–C base triple formation. Currently, an unmodified T base is often incorporated into PNAs to recognize a Watson–Crick A–U pair through major-groove T·A–U base triple formation. A substitution of the 5-methyl group in T by hydrogen and halogen atoms (F, Cl, Br, and I) causes a decrease of the pK(a) of N3 nitrogen atom, which may result in improved hydrogen bonding in addition to enhanced base stacking interactions. Here, we synthesized a series of PNAs incorporating uracil and halouracils, followed by binding studies by non-denaturing polyacrylamide gel electrophoresis, circular dichroism, and thermal melting. Our results suggest that replacing T with uracil and halouracils may enhance the recognition of an A–U pair by PNA·RNA(2) triplex formation in a sequence-dependent manner, underscoring the importance of local stacking interactions. Incorporating bromouracils and chlorouracils into a PNA results in a significantly reduced pH dependence of triplex formation even for PNAs containing C bases, likely due to an upshift of the apparent pK(a) of N3 atoms of C bases. Thus, halogenation and other chemical modifications may be utilized to enhance hydrogen bonding of the adjacent base triples and thus triplex formation. Furthermore, our experimental and computational modelling data suggest that PNA·RNA(2) triplexes may be stabilized by incorporating a (Br)UL step but not an L(Br)U step, in dsRNA-binding PNAs.",2018 Sep 6,"['Patil, Kiran M', 'Toh, Desiree-Faye Kaixin', 'Yuan, Zhen', 'Meng, Zhenyu', 'Shu, Zhiyu', 'Zhang, Haiping', 'Ong, Alan\xa0Ann\xa0Lerk', 'Krishna, Manchugondanahalli S', 'Lu, Lanyuan', 'Lu, Yunpeng', 'Chen, Gang']",Nucleic Acids Res,,,True
f633ec24c26ab3db499227405678f21cc6ab2af5,PMC,Incorporating uracil and 5-halouracils into short peptide nucleic acids for enhanced recognition of A–U pairs in dsRNAs,http://dx.doi.org/10.1093/nar/gky631,PMC6125629,30011039,CC BY-NC,"Double-stranded RNA (dsRNA) structures form triplexes and RNA-protein complexes through binding to single-stranded RNA (ssRNA) regions and proteins, respectively, for diverse biological functions. Hence, targeting dsRNAs through major-groove triplex formation is a promising strategy for the development of chemical probes and potential therapeutics. Short (e.g., 6–10 mer) chemically-modified Peptide Nucleic Acids (PNAs) have been developed that bind to dsRNAs sequence specifically at physiological conditions. For example, a PNA incorporating a modified base thio-pseudoisocytosine (L) has an enhanced recognition of a G–C pair in an RNA duplex through major-groove L·G–C base triple formation at physiological pH, with reduced pH dependence as observed for C(+)·G–C base triple formation. Currently, an unmodified T base is often incorporated into PNAs to recognize a Watson–Crick A–U pair through major-groove T·A–U base triple formation. A substitution of the 5-methyl group in T by hydrogen and halogen atoms (F, Cl, Br, and I) causes a decrease of the pK(a) of N3 nitrogen atom, which may result in improved hydrogen bonding in addition to enhanced base stacking interactions. Here, we synthesized a series of PNAs incorporating uracil and halouracils, followed by binding studies by non-denaturing polyacrylamide gel electrophoresis, circular dichroism, and thermal melting. Our results suggest that replacing T with uracil and halouracils may enhance the recognition of an A–U pair by PNA·RNA(2) triplex formation in a sequence-dependent manner, underscoring the importance of local stacking interactions. Incorporating bromouracils and chlorouracils into a PNA results in a significantly reduced pH dependence of triplex formation even for PNAs containing C bases, likely due to an upshift of the apparent pK(a) of N3 atoms of C bases. Thus, halogenation and other chemical modifications may be utilized to enhance hydrogen bonding of the adjacent base triples and thus triplex formation. Furthermore, our experimental and computational modelling data suggest that PNA·RNA(2) triplexes may be stabilized by incorporating a (Br)UL step but not an L(Br)U step, in dsRNA-binding PNAs.",2018 Sep 6,"['Patil, Kiran M', 'Toh, Desiree-Faye Kaixin', 'Yuan, Zhen', 'Meng, Zhenyu', 'Shu, Zhiyu', 'Zhang, Haiping', 'Ong, Alan\xa0Ann\xa0Lerk', 'Krishna, Manchugondanahalli S', 'Lu, Lanyuan', 'Lu, Yunpeng', 'Chen, Gang']",Nucleic Acids Res,,,True
abb4c06114edb9aa57132be9201478ac965a56ba,PMC,"The methyltransferase domain of the Sudan ebolavirus L protein specifically targets internal adenosines of RNA substrates, in addition to the cap structure",http://dx.doi.org/10.1093/nar/gky637,PMC6125687,30192980,CC BY-NC,"Mononegaviruses, such as Ebola virus, encode an L (large) protein that bears all the catalytic activities for replication/transcription and RNA capping. The C-terminal conserved region VI (CRVI) of L protein contains a K-D-K-E catalytic tetrad typical for 2’O methyltransferases (MTase). In mononegaviruses, cap-MTase activities have been involved in the 2’O methylation and N7 methylation of the RNA cap structure. These activities play a critical role in the viral life cycle as N7 methylation ensures efficient viral mRNA translation and 2’O methylation hampers the detection of viral RNA by the host innate immunity. The functional characterization of the MTase+CTD domain of Sudan ebolavirus (SUDV) revealed cap-independent methyltransferase activities targeting internal adenosine residues. Besides this, the MTase+CTD also methylates, the N7 position of the cap guanosine and the 2’O position of the n1 guanosine provided that the RNA is sufficiently long. Altogether, these results suggest that the filovirus MTases evolved towards a dual activity with distinct substrate specificities. Whereas it has been well established that cap-dependent methylations promote protein translation and help to mimic host RNA, the characterization of an original cap-independent methylation opens new research opportunities to elucidate the role of RNA internal methylations in the viral replication.",2018 Sep 6,"['Martin, Baptiste', 'Coutard, Bruno', 'Guez, Théo', 'Paesen, Guido C', 'Canard, Bruno', 'Debart, Françoise', 'Vasseur, Jean-Jacques', 'Grimes, Jonathan M', 'Decroly, Etienne']",Nucleic Acids Res,,,True
c46b171cf1c9b3e37b52549cb2c4356b5058f0c2,PMC,"The methyltransferase domain of the Sudan ebolavirus L protein specifically targets internal adenosines of RNA substrates, in addition to the cap structure",http://dx.doi.org/10.1093/nar/gky637,PMC6125687,30192980,CC BY-NC,"Mononegaviruses, such as Ebola virus, encode an L (large) protein that bears all the catalytic activities for replication/transcription and RNA capping. The C-terminal conserved region VI (CRVI) of L protein contains a K-D-K-E catalytic tetrad typical for 2’O methyltransferases (MTase). In mononegaviruses, cap-MTase activities have been involved in the 2’O methylation and N7 methylation of the RNA cap structure. These activities play a critical role in the viral life cycle as N7 methylation ensures efficient viral mRNA translation and 2’O methylation hampers the detection of viral RNA by the host innate immunity. The functional characterization of the MTase+CTD domain of Sudan ebolavirus (SUDV) revealed cap-independent methyltransferase activities targeting internal adenosine residues. Besides this, the MTase+CTD also methylates, the N7 position of the cap guanosine and the 2’O position of the n1 guanosine provided that the RNA is sufficiently long. Altogether, these results suggest that the filovirus MTases evolved towards a dual activity with distinct substrate specificities. Whereas it has been well established that cap-dependent methylations promote protein translation and help to mimic host RNA, the characterization of an original cap-independent methylation opens new research opportunities to elucidate the role of RNA internal methylations in the viral replication.",2018 Sep 6,"['Martin, Baptiste', 'Coutard, Bruno', 'Guez, Théo', 'Paesen, Guido C', 'Canard, Bruno', 'Debart, Françoise', 'Vasseur, Jean-Jacques', 'Grimes, Jonathan M', 'Decroly, Etienne']",Nucleic Acids Res,,,False
52cc80efbb69d917fa6d4ad3f34f73124ea27ee8,PMC,Epidemiology and clinical outcomes of feline immunodeficiency virus and feline leukaemia virus in client-owned cats in New Zealand,http://dx.doi.org/10.1177/2055116917729311,PMC6125856,30202540,CC BY-NC,"OBJECTIVES: The objectives were to collect baseline data on the occurrence, testing and vaccination practices, and clinical outcomes of feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) in New Zealand METHODS: A cross-sectional survey of 423 veterinary practices in New Zealand was performed to collect data on FeLV and FIV testing and vaccination during the 2015 calendar year. Clinical records from 572 cats tested using a point-of-care ELISA at a first-opinion veterinary practice between 7 April 2010 and 23 June 2016 were also obtained and multivariable logistic regression models were constructed to identify risk factors for test positivity. Survival times were estimated using Kaplan–Meier methods. RESULTS: The survey was completed by 112 clinics (26.4%) of which 72 performed in-house testing. Of the 2125 tests performed, 56 (2.6%) were positive for FeLV and 393 (18.5%) were positive for FIV. Fewer than 1% of cats were vaccinated for FeLV, with veterinarians citing low perceived prevalence as the primary reason for not vaccinating. Being male compared with being female and having clinical evidence of immunosuppression were significant risk factors for both FeLV and FIV test positivity. The median survival times of FeLV and FIV test-positive cats were 10 days (95% confidence interval [CI] 0–16) and 650 days (95% CI 431–993), respectively. CONCLUSIONS AND RELEVANCE: Testing and vaccination for FeLV and FIV in New Zealand appears targeted towards high-risk animals, which may bias prevalence estimates. Baseline data should be monitored for changes in FeLV epidemiology now commercial vaccines are no longer available.",2017 Sep 19,"['Luckman, Claire', 'Gates, M Carolyn']",JFMS Open Rep,,,True
6fccba98b953f6f90decbf7e76a279f47f6a372b,PMC,Establishing research priorities to improve the One Health efficacy of Australian general practitioners and veterinarians with regard to zoonoses: A modified Delphi survey,http://dx.doi.org/10.1016/j.onehlt.2018.08.001,PMC6127845,30197925,CC BY-NC-ND,"While general medical practitioners (GPs) and veterinarians are often the first line responders in the face of a disease outbreak, pathways to improving the One Health efficacy of these clinicians remain unclear. A two-phase modified Delphi survey of professionals with known expertise in One Health (‘expert panel’) was used to 1) identify key knowledge, attitudes and practices (KAPs) of GPs and veterinarians that would be consistent with a One Health approach to zoonoses; and 2) determine priorities for future surveys with Australian GPs and veterinarians to identify important gaps that impede effective diagnosis and management of zoonoses. A list of 13 topics/sub-topics, as well as a list of 25 specific zoonotic diseases/agents emerged from the first phase of the survey. In the second phase the expert panel identified general knowledge of the clinical aspects and epidemiological aspects of zoonoses, as well as risk management practices, as the most important KAPs and research priorities for both GPs and veterinarians. In terms of diseases, the expert panel regarded knowledge of Hendra virus, Q fever, Australian bat lyssavirus (ABLV), anthrax and Brucella suis most important for veterinarians, whilst for GPs, Q fever, gastrointestinal/foodborne diseases, influenza, ABLV and local vector-borne diseases were found to be most important by the expert panel. Some differences were noted in terms of prioritization of topics/sub-topics and diseases/agents according to expert background (veterinary and non-veterinary). The Delphi survey technique enabled efficient collection of data from a diverse range of One Health ‘experts’/specialists and provided clear priorities for proposed future research, and potentially for educational interventions to improve One Health efficacy of clinicians.",2018 Aug 30,"['Steele, Sandra G.', 'Booy, Robert', 'Mor, Siobhan M.']",One Health,,,False
6aa4476feb03bb59ab1cd8452bb48c77c9816a73,PMC,Understanding of the functional role(s) of the Activating Transcription Factor 4(ATF4) in HIV regulation and production,http://dx.doi.org/10.5483/BMBRep.2018.51.8.054,PMC6130831,29636121,CC BY-NC,"The activating transcription factor (ATF) 4 belongs to the ATF/CREB (cAMP Response Element Binding bZIP [Basic Leucine Zipper]) transcription factor family, and plays a central role in the UPR (Unfolded Protein Response) process in cells. The induction of ATF4 expression has previously been shown to increase the replication of HIV-1. However, the detailed mechanism underlying this effect and the factors involved in the regulation of ATF4 function are still unknown. Here, we demonstrate first that knocking out ATF4 using siRNA shows a strong negative effect on HIV-1 production, indicating that ATF4 is a functional positive cellular factor in HIV-1 production. To determine the mechanism by which ATF4 regulates the HIV-1 life cycle, we assessed the effect of the overexpression of wild type ATF4 and its various derivatives on HIV-1 LTR-mediated transcriptional activation and the production of HIV-1 particles. This effect was studied through co-transfection experiments with either reporter vectors or proviral DNA. We found that the N-terminal domains of ATF4 are involved in HIV-1 LTR-mediated transcriptional activation, and thus in HIV-1 production.",2018 Aug 31,"['Lee, Seong-Deok', 'Yu, Kyung-Lee', 'Park, Seong-Hyun', 'Jung, Yu-Mi', 'Kim, Min-Jeong', 'You, Ji-Chang']",BMB Rep,,,True
e475b16e9dfbd736eba3f5fdbcebf2ffd52e556c,PMC,Understanding of the functional role(s) of the Activating Transcription Factor 4(ATF4) in HIV regulation and production,http://dx.doi.org/10.5483/BMBRep.2018.51.8.054,PMC6130831,29636121,CC BY-NC,"The activating transcription factor (ATF) 4 belongs to the ATF/CREB (cAMP Response Element Binding bZIP [Basic Leucine Zipper]) transcription factor family, and plays a central role in the UPR (Unfolded Protein Response) process in cells. The induction of ATF4 expression has previously been shown to increase the replication of HIV-1. However, the detailed mechanism underlying this effect and the factors involved in the regulation of ATF4 function are still unknown. Here, we demonstrate first that knocking out ATF4 using siRNA shows a strong negative effect on HIV-1 production, indicating that ATF4 is a functional positive cellular factor in HIV-1 production. To determine the mechanism by which ATF4 regulates the HIV-1 life cycle, we assessed the effect of the overexpression of wild type ATF4 and its various derivatives on HIV-1 LTR-mediated transcriptional activation and the production of HIV-1 particles. This effect was studied through co-transfection experiments with either reporter vectors or proviral DNA. We found that the N-terminal domains of ATF4 are involved in HIV-1 LTR-mediated transcriptional activation, and thus in HIV-1 production.",2018 Aug 31,"['Lee, Seong-Deok', 'Yu, Kyung-Lee', 'Park, Seong-Hyun', 'Jung, Yu-Mi', 'Kim, Min-Jeong', 'You, Ji-Chang']",BMB Rep,,,False
3f65b990d1f24de2bf3cd52d8559e8ccba9961af,PMC,Assessing health burden risk and control effect on dengue fever infection in the southern region of Taiwan,http://dx.doi.org/10.2147/IDR.S169820,PMC6132233,30233221,CC BY-NC,"BACKGROUND: The high prevalence of dengue in Taiwan and the consecutive large dengue outbreaks in the period 2014–2015 suggest that current control interventions are suboptimal. Understanding the effect of control effort is crucial to inform future control strategies. OBJECTIVES: We developed a framework to measure season-based health burden risk from 2001 to 2014. We reconstructed various intervention coverage to assess the attributable effect of dengue infection control efforts. MATERIALS AND METHODS: A dengue–mosquito–human transmission dynamic was used to quantify the vector–host interactions and to estimate the disease epidemics. We used disability-adjusted life years (DALYs) to assess health burden risk. A temperature-basic reproduction number (R(0))–DALYs relationship was constructed to examine the potential impacts of temperature on health burden. Finally, a health burden risk model linked a control measure model to evaluate the effect of dengue control interventions. RESULTS: We showed that R(0) and DALYs peaked at 25°C with estimates of 2.37 and 1387, respectively. Results indicated that most dengue cases occurred in fall with estimated DALYs of 323 (267–379, 95% CI) at 50% risk probability. We found that repellent spray had by far the largest control effect with an effectiveness of ~71% in all seasons. Pesticide spray and container clean-up have both made important contributions to reducing prevalence/incidence. Repellent, pesticide spray, container clean-up together with Wolbachia infection suppress dengue outbreak by ~90%. CONCLUSION: Our presented modeling framework provides a useful tool to measure dengue health burden risk and to quantify the effect of dengue control on dengue infection prevalence and disease incidence in the southern region of Taiwan.",2018 Sep 6,"['Cheng, Yi-Hsien', 'Lin, Yi-Jun', 'Chen, Szu-Chieh', 'You, Shu-Han', 'Chen, Wei-Yu', 'Hsieh, Nan-Hung', 'Yang, Ying-Fei', 'Liao, Chung-Min']",Infect Drug Resist,,,True
9b992705cb74945a376dfbcf616b8c213b0d6678,PMC,Analysis of seasonal tendencies in pediatric Henoch–Schönlein purpura and comparison with outbreak of infectious diseases,http://dx.doi.org/10.1097/MD.0000000000012217,PMC6133644,30200139,CC BY-NC,"Henoch–Schönlein purpura (HSP) is one of the most common vasculitis in children. This study was aimed at identifying seasonal trends and epidemiologic features of pediatric HSP patients through public data to analyze the correlation of HSP and prevalence of a specific respiratory or enteric virus. We extracted information on pediatric HSP patients categorized into 4 age groups and data on 8 respiratory and 4 enteric viruses were extracted from national data. We used the decomposition of time series analysis and correlation analysis to identify the incidence of HSP and the prevalence of each virus. From 2013 to 2016, 16,940 patients under the age of 18 were diagnosed with HSP in Korea, 6203 (36.6%) were diagnosed with HSP in middle childhood. Spring had the largest number of patients (5252, 31.0%), and summer had the smallest number of patients (3224, 19.0%). The largest and smallest number of cases occurred in March (1949, 11.5%) and August (959, 5.7%), respectively. However, among the adolescents, more patients were diagnosed in the summer (985, 24.8%) than in the fall (760, 19.1%). The positive detection counts of most viruses showed apparent seasonal variations. Depending on the age group, the epidemic patterns of influenza and rotaviruses were temporally and statistically similar to that of HSP. We have confirmed that the occurrence of pediatric HSP in Korea shows a seasonal tendency, which is age-dependent and related to exposure to infectious agents and suggest some respiratory or enteric viruses may play an important role in pathophysiology.",2018 Sep 7,"['Hwang, Hyun Ho', 'Lim, In Seok', 'Choi, Byung-Sun', 'Yi, Dae Yong']",Medicine (Baltimore),,,True
511cd67bbeb3835b5feb25ace6582b7d758debe4,PMC,Antiviral therapeutic approaches for human rhinovirus infections,http://dx.doi.org/10.2217/fvl-2018-0016,PMC6136076,30245735,CC BY-NC-ND,"Human rhinoviruses are the primary etiological agent of the common cold. This infection can be mild and self-limiting in immunocompetent hosts, but can be associated with bronchiolitis in infants, pneumonia in the immunosuppressed and exacerbations of pre-existing pulmonary conditions such as asthma or chronic obstructive pulmonary disease. Many of these conditions can place significant economic costs upon healthcare infrastructure. There is currently no licensed vaccine for rhinovirus, as the large variety of rhinovirus serotypes has posed significant challenges for research. In this review, we discuss current knowledge around antiviral drugs and small molecule inhibitors of rhinovirus infection, as well as antiviral host defense peptides as exciting prospects to approach the development of novel therapeutics which target human rhinovirus.",2018 Jul 12,"['Casanova, Victor', 'Sousa, Filipa H', 'Stevens, Craig', 'Barlow, Peter G']",Future Virol,,,True
3de90c8c18dbed90408c4a5cc5cb94f856c9f637,PMC,Identification of Cystoisospora ohioensis in a Diarrheal Dog in Korea,http://dx.doi.org/10.3347/kjp.2018.56.4.371,PMC6137296,30196670,CC BY-NC,"A 3-month-old female Maltese puppy was hospitalized with persistent diarrhea in a local veterinary clinic. Blood chemistry and hematology profile were analyzed and fecal smear was examined. Diarrheal stools were examined in a diagnostic laboratory, using multiplex real-time polymerase chain reaction (PCR) against 23 diarrheal pathogens. Sequence analysis was performed using nested PCR amplicon of 18S ribosomal RNA. Coccidian oocysts were identified in the fecal smear. Although multiplex real-time PCR was positive for Cyclospora cayetanensis, the final diagnosis was Cystoisospora ohioensis infection, confirmed by phylogenetic analysis of 18S rRNA. To our knowledge, this the first case report of C. ohioensis in Korea, using microscopic examination and phylogenetic analysis.",2018 Aug 31,"['Lee, Sangmin', 'Kim, Junki', 'Cheon, Doo-Sung', 'Moon, Eun-A', 'Seo, Dong Joo', 'Jung, Soontag', 'Shin, Hansaem', 'Choi, Changsun']",Korean J Parasitol,,,True
864aae86243c04c5cec3dff93a6d51d29a43da94,PMC,Comparing the outcomes of different postgraduate year training programs in Taiwan,http://dx.doi.org/10.1016/j.bj.2016.01.006,PMC6138378,27013455,CC BY-NC-ND,"BACKGROUND: Postgraduate year training programs play an important role in the development of a comprehensive medical education. The goal of these training programs is to inculcate in physicians the expected level of skill in patient care. After the initiation of such programs in the USA, Europe, and Japan, studies were conducted in Taiwan to investigate relevant training methods, and a training system was established in 2003. Beginning with 3-month programs, followed by 6-month programs, the programs were constantly modified and enhanced by the establishment of the 1-year training program in 2011. This year was the transition period from the 6-month programs to the 1-year programs. METHODS: We used a 50-item multiple choice question (MCQ) test and six 10-min stations for objective structured clinical examination (OSCE), which was composed of four stations relating to standardized patients and two stations concerning the clinical skill evaluation, to evaluate the learning results of the trainees. The trainees were divided into four groups according to the training program. RESULTS: There was no significant difference between the performance of the 6 months and 1-year groups. The p values were 0.424 in the MCQ test and 0.082 in the OSCE evaluation. CONCLUSION: A well-designed postgraduate training program should develop trainees’ competencies. The results of this study may provide useful insight for ways to improve the design of training programs. Further investigation to better understand the impact of different programs is warranted.",2015 Dec 9,"['Hsu, Peng-Wei', 'Hsieh, Ming-Ju', 'Fu, Ren-Huei', 'Huang, Jing-Long', 'Liao, Mei-Chen', 'Lee, Shih-Tseng']",Biomed J,,,False
d3379dc025c78ba33cd4228ba627b627534f8766,PMC,Evaluation of visual triage for screening of Middle East respiratory syndrome coronavirus patients,http://dx.doi.org/10.1016/j.nmni.2018.08.008,PMC6138856,30224971,CC BY-NC-ND,"The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in September 2012 in Saudi Arabia had attracted the attention of the global health community. In 2017 the Saudi Ministry of Health released a visual triage system with scoring to alert healthcare workers in emergency departments (EDs) and haemodialysis units for the possibility of occurrence of MERS-CoV infection. We performed a retrospective analysis of this visual score to determine its sensitivity and specificity. The study included all cases from 2014 to 2017 in a MERS-CoV referral centre in Riyadh, Saudi Arabia. During the study period there were a total of 2435 suspected MERS cases. Of these, 1823 (75%) tested negative and the remaining 25% tested positive for MERS-CoV by PCR assay. The application of the visual triage score found a similar percentage of MERS-CoV and non–MERS-CoV patients, with each score from 0 to 11. The percentage of patients with a cutoff score of ≥4 was 75% in patients with MERS-CoV infection and 85% in patients without MERS-CoV infection (p 0.0001). The sensitivity and specificity of this cutoff score for MERS-CoV infection were 74.1% and 18.6%, respectively. The sensitivity and specificity of the scoring system were low, and further refinement of the score is needed for better prediction of MERS-CoV infection.",2018 Aug 11,"['Alfaraj, S.H.', 'Al-Tawfiq, J.A.', 'Gautret, P.', 'Alenazi, M.G.', 'Asiri, A.Y.', 'Memish, Z.A.']",New Microbes New Infect,,,False
425e0ee111062385cb630f0ea0659608d5fbec5c,PMC,Nasopharyngeal isolates and their clinical impact on young children with asthma: a pilot study,http://dx.doi.org/10.2147/JAA.S169966,PMC6140756,30254474,CC BY-NC,"INTRODUCTION: Respiratory infections have significant effects on childhood asthma. Viral respiratory infections, such as rhinovirus and respiratory syncytial virus are likely to be important in the development and exacerbation of asthma. In this study, we investigated the nasopharyngeal colonization in children with asthma to determine the prevalence of pathogens and their contribution to respiratory symptoms and airway resistance during winter. METHODS: From December 2016 to March 2017, 50 nasopharyngeal specimens were collected from 18 patients (age, 5.0±1.1 years) with asthma and 9 specimens from 9 control children (age, 4.9±1.0 years). Samples were tested for 19 viruses and 7 bacteria, using multiplex real-time PCR. Respiratory disease markers included the Global Asthma Network Questionnaire, the Common-Cold Questionnaire, the Global Initiative for Asthma assessment of asthma control, and the airway resistance at 5 Hz by forced-oscillation technique. RESULTS: The most commonly isolated organisms in both groups (patients and controls) were Streptococcus pneumoniae, Haemophilus influenzae, and rhinovirus. Most patients had multiple isolates (median, 3.5; range, 1–5), which changed during the study period. Types of isolates were 4 bacteria (S. pneumoniae, H. influenzae, Bordetella pertussis, and Bordetella parapertussis) and 6 viruses (rhinovirus, enterovirus, metapneumovirus, adenovirus, coronaviruses, and parainfluenza viruses). Similar isolates, including influenza A-H3 virus and bocavirus, were detected in the controls. Of the 9 patients with “wheezing disturbing sleep ≥1 per week”, 6 had rhinovirus, 2 coronaviruses, and 1 no detectable viruses. Patients with mild common cold symptoms had significantly higher airway resistance at 5 Hz z-score (P=0.025). CONCLUSION: Multiple respiratory pathogens were isolated from many patients with asthma, which appeared to contribute to disease symptoms and airway resistance. Minimizing children’s exposure to respiratory pathogens might be beneficial, especially during winter.",2018 Sep 12,"['Alsuwaidi, Ahmed R', 'Alkalbani, Alia M', 'Alblooshi, Afaf', 'George, Junu', 'Albadi, Ghaya', 'Kamal, Salwa M', 'Narchi, Hassib', 'Souid, Abdul-Kader']",J Asthma Allergy,,,True
cdffb72af0749246fd5f957fda4e793e29911a83,PMC,Insights into the development of chemical probes for RNA,http://dx.doi.org/10.1093/nar/gky718,PMC6144806,30102391,CC BY-NC,"Over the past decade, the RNA revolution has revealed thousands of non-coding RNAs that are essential for cellular regulation and are misregulated in disease. While the development of methods and tools to study these RNAs has been challenging, the power and promise of small molecule chemical probes is increasingly recognized. To harness existing knowledge, we compiled a list of 116 ligands with reported activity against RNA targets in biological systems (R-BIND). In this survey, we examine the RNA targets, design and discovery strategies, and chemical probe characterization techniques of these ligands. We discuss the applicability of current tools to identify and evaluate RNA-targeted chemical probes, suggest criteria to assess the quality of RNA chemical probes and targets, and propose areas where new tools are particularly needed. We anticipate that this knowledge will expedite the discovery of RNA-targeted ligands and the next phase of the RNA revolution.",2018 Sep 19,"['Morgan, Brittany S', 'Forte, Jordan E', 'Hargrove, Amanda E']",Nucleic Acids Res,,,True
cc9cf437db5ffe6c085e9b72a6d20d067a3c7c03,PMC,Small synthetic molecule-stabilized RNA pseudoknot as an activator for –1 ribosomal frameshifting,http://dx.doi.org/10.1093/nar/gky689,PMC6144811,30085309,CC BY-NC,"Programmed –1 ribosomal frameshifting (−1PRF) is a recoding mechanism to make alternative proteins from a single mRNA transcript. −1PRF is stimulated by cis-acting signals in mRNA, a seven-nucleotide slippery sequence and a downstream secondary structure element, which is often a pseudoknot. In this study we engineered the frameshifting pseudoknot from the mouse mammary tumor virus to respond to a rationally designed small molecule naphthyridine carbamate tetramer (NCTn). We demonstrate that NCTn can stabilize the pseudoknot structure in mRNA and activate –1PRF both in vitro and in human cells. The results illustrate how NCTn-inducible –1PRF may serve as an important component of the synthetic biology toolbox for the precise control of gene expression using small synthetic molecules.",2018 Sep 19,"['Matsumoto, Saki', 'Caliskan, Neva', 'Rodnina, Marina V', 'Murata, Asako', 'Nakatani, Kazuhiko']",Nucleic Acids Res,,,True
7e757d19351d6680088ee7343c19873de2e1bcfa,PMC,Small synthetic molecule-stabilized RNA pseudoknot as an activator for –1 ribosomal frameshifting,http://dx.doi.org/10.1093/nar/gky689,PMC6144811,30085309,CC BY-NC,"Programmed –1 ribosomal frameshifting (−1PRF) is a recoding mechanism to make alternative proteins from a single mRNA transcript. −1PRF is stimulated by cis-acting signals in mRNA, a seven-nucleotide slippery sequence and a downstream secondary structure element, which is often a pseudoknot. In this study we engineered the frameshifting pseudoknot from the mouse mammary tumor virus to respond to a rationally designed small molecule naphthyridine carbamate tetramer (NCTn). We demonstrate that NCTn can stabilize the pseudoknot structure in mRNA and activate –1PRF both in vitro and in human cells. The results illustrate how NCTn-inducible –1PRF may serve as an important component of the synthetic biology toolbox for the precise control of gene expression using small synthetic molecules.",2018 Sep 19,"['Matsumoto, Saki', 'Caliskan, Neva', 'Rodnina, Marina V', 'Murata, Asako', 'Nakatani, Kazuhiko']",Nucleic Acids Res,,,True
acb8da60c4ee0bcc69d4c1da2786a429e7a374ee,PMC,Differential chemokine expression patterns in tonsillar disease,http://dx.doi.org/10.14639/0392-100X-1743,PMC6146581,30197422,CC BY-NC-ND,"Expression profiles of CXC- and CC-chemokines in various forms of tonsillar disease were studied to evaluate whether certain chemokines play a predominant role in a specific subset of tonsillar disease. Total RNA was isolated from 89 biopsies (21 hyperplastic palatine tonsils, 25 adenoids, 16 chronic inflammatory palatine tonsils and 27 chronic inflammatory palatine tonsils with histological prove of acute inflammation), reverse transcribed and subjected to PCR amplifying IL-8, Gro-alpha, eotaxin-1, eotaxin-2, MCP-3, MCP-4 and RANTES. 2% agarose gel electrophoresis revealed a predominance of IL-8 in the chronic inflammatory palatine tonsil group compared to tonsillar hyperplasia. Furthermore, eotaxin-2 was strongly overexpressed in adenoid samples compared to chronic inflammatory specimens. Our data suggest that the majority of diseases related to adenoid formation are mediated via an eotaxin-2 expression, whereas chronic inflammatory tonsillitis is associated with IL-8 upregulation. These data imply that adenoids are related to a Th-2, and chronic inflammatory tonsillitis to a Th-1 based immune response.",2018 Aug,"['Mandapathil, M.', 'H.Beier, U.', 'Graefe, H.', 'Kröger, B.', 'Hedderich, J.', 'Maune, S.', 'Meyer, J. E']",Acta Otorhinolaryngol Ital,,,True
0aa4edc168fd9bf7ba7efee20dbeb007c26b1beb,PMC,Phylogeny of bovine norovirus in Egypt based on VP2 gene,http://dx.doi.org/10.1016/j.ijvsm.2018.04.005,PMC6147391,30255078,CC BY-NC-ND,"Bovine norovirus (BNoV) has emerged as a viral pathogen that causes a gastrointestinal illness and diarrhea in cattle. Despite its worldwide distribution, very little information is known about BNoV in Africa. In this study, BNoV was detected in 27.6% (8/29) of tested fecal materials, collected from sporadic cases of diarrheic calves, using the reverse transcription-polymerase chain reaction (RT-PCR) and primers that target RNA dependent RNA polymerase gene. Additionally, one primer pair was designed to flank the BNoV-VP2 (small capsid protein) gene for molecular analysis. Study VP2 sequences were phylogenetically-related to BNoV-GIII.2 (Newbury2-like) genotype, which is highly prevalent all over the world. However, they were separated within the cluster and one strain (41FR) grouped with recombinant GIII.P1/GIII.2 strains. Compared to reference VP2 sequences, 14 amino acid substitution mutations were found to be unique to our strains. The study confirms that BNoV is currently circulating among diarrheic calves of Egypt and also characterizes its ORF3 (VP2) genetically. The status of BNoV should be continuously evaluated in Egypt for effective prevention and control.",2018 Apr 13,"['Mohamed, Fakry F.', 'Ktob, Gamelat K.F.', 'Ismaeil, Mohamed E.A.', 'Ali, Ahmed A.H.', 'Goyal, Sagar M.']",Int J Vet Sci Med,,,False
f91911b6a25c970324854df7b87c550ae7fb878f,PMC,First identification of a single amino acid change in the spike protein region of feline coronavirus detected from a coronavirus-associated cutaneous nodule in a cat,http://dx.doi.org/10.1177/2055116918801385,PMC6149024,30263143,CC BY-NC,"CASE SUMMARY: A 32-month-old spayed female Singapura cat presented with a non-pruritic erythematous nodule on the upper lip. The cat also had multiple nodules in the liver but exhibited no other clinical signs consistent with classical feline infectious peritonitis (FIP), such as pleural effusion or ascites, uveitis or neurological symptoms. Histopathological and immunohistochemical analyses of the cutaneous nodule revealed pyogranulomatous dermatitis with intralesional macrophages laden with feline coronavirus (FCoV) antigen. Real-time reverse transcription (RT)-PCR of a cutaneous sample revealed a single nucleotide substitution in the spike protein gene of FCoV (mutation M1058L), which is consistent with an FCoV genotype commonly associated with FIP. The cat received a blood transfusion and supportive therapy, but the owner declined to continue the treatments owing to poor response. The cat was lost to follow-up 5 months after discharge. RELEVANCE AND NOVEL INFORMATION: This report describes a case of a coronavirus-associated cutaneous nodule in which the evidence of amino acid changes in the spike protein gene identified by RT-PCR were consistent with an FCoV genotype commonly seen in cases of FIP. To the best of our knowledge, this is the first report of a case of cutaneous disease associated with the mutated FCoV that was confirmed by molecular diagnostic testing.",2018 Sep 20,"['Osumi, Takafumi', 'Mitsui, Ikki', 'Leutenegger, Christian M', 'Okabe, Ryo', 'Ide, Kaori', 'Nishifuji, Koji']",JFMS Open Rep,,,True
dac4e5ddd4e1b0a3ec755a573674371f724462a8,PMC,Susceptibility of Chikungunya Virus to Inactivation by Heat and Commercially and World Health Organization-Recommended Biocides,http://dx.doi.org/10.1093/infdis/jiy359,PMC6151073,29917109,CC BY-NC-ND,"Despite increasing clinical relevance of Chikungunya virus (CHIKV) infection, caused by a rapidly emerging pathogen, recommended guidelines for its inactivation do not exist. In this study, we investigated the susceptibility of CHIKV to inactivation by heat and commercially available hand, surface, and World Health Organization-recommended disinfectants to define CHIKV prevention protocols for healthcare systems.",2018 Nov 1,"['Franz, Sergej', 'Friesland, Martina', 'Passos, Vânia', 'Todt, Daniel', 'Simmons, Graham', 'Goffinet, Christine', 'Steinmann, Eike']",J Infect Dis,,,True
ddcdf307d475ccd519f683df9c52d537459c634d,PMC,Susceptibility of Chikungunya Virus to Inactivation by Heat and Commercially and World Health Organization-Recommended Biocides,http://dx.doi.org/10.1093/infdis/jiy359,PMC6151073,29917109,CC BY-NC-ND,"Despite increasing clinical relevance of Chikungunya virus (CHIKV) infection, caused by a rapidly emerging pathogen, recommended guidelines for its inactivation do not exist. In this study, we investigated the susceptibility of CHIKV to inactivation by heat and commercially available hand, surface, and World Health Organization-recommended disinfectants to define CHIKV prevention protocols for healthcare systems.",2018 Nov 1,"['Franz, Sergej', 'Friesland, Martina', 'Passos, Vânia', 'Todt, Daniel', 'Simmons, Graham', 'Goffinet, Christine', 'Steinmann, Eike']",J Infect Dis,,,False
dedc4700c705e92f673764ae9959fac57f1e2e7b,PMC,Recomendaciones para la atención del paciente con neumonía adquirida en la comunidad en los Servicios de Urgencias,,PMC6159381,29619807,CC BY-NC,"The incidence of community-acquired pneumonia (CAP) ranges from 2-15 cases / 1,000 inhabitants / year, being higher in those older than 65 years and in patients with high comorbidity. Around 75% of all CAP diagnosed are treated in the Emergency Department (ED). The CAP represents the main cause for sepsis and septic shock in ED, and the most frequent cause of death and admission to the Intensive Care Unit (ICU) due to infectious disease. Overall mortality is 10-14% according to age and associated risk factors. Forty to 60% of CAP will require hospital admission, including observation units (with very variable ranges from 22-65% according to centers, seasonal of the year and patients´ characteristics). Between the admissions, 2-10% will be in the ICU. All of previously mentioned reflects the importance of the CAP in the ED, as well as the “impact of the emergency care on the patient with CAP”, as it is the establishment where the initial, but key decisions, are made and could condition the outcome of the illness. It is known the great variability among physicians in the diagnostic and therapeutic management of CAP, which is one of the reasons that explains the great differences in the admission rates, achievement of the microbiological diagnosis, request for complementary studies, the choice of antimicrobial treatment, or the diversity of applied care. In this sense, the implementation of clinical practice guidelines with the use of the severity scores and the new tools available, such as biomarkers, can improve patient care with CAP in ED. Therefore, a multidisciplinary group of emergency professionals and specialists involved in the care process of CAP has designed a guideline with several recommendations for decisions-making during the key moments in patients with CAP attended in the ED.",2018 Apr 12,"['Julián-Jiménez, Agustín', 'Valero, Inmaculada Adán', 'López, Alicia Beteta', 'Martín, Luis Miguel Cano', 'Rodríguez, Olga Fernández', 'Díaz, Rafael Rubio', 'Berrocal, Mª Antonia Sepúlveda', 'del Castillo, Juan González', 'González, Francisco Javier Candel', None]",Rev Esp Quimioter,,,True
4bf7428a3d7bd1625f0e945398eb8ff045ea4b71,PMC,"Genetic, Transcriptome, Proteomic, and Epidemiological Evidence for Blood-Brain Barrier Disruption and Polymicrobial Brain Invasion as Determinant Factors in Alzheimer’s Disease",http://dx.doi.org/10.3233/ADR-170017,PMC6159731,30480234,CC BY-NC,"Diverse pathogens are detected in Alzheimer’s disease (AD) brains. A bioinformatics survey showed that AD genome-wide association study (GWAS) genes (localized in bone marrow, immune locations and microglia) relate to multiple host/pathogen interactomes (Candida albicans, Cryptococcus neoformans, Bornavirus, Borrelia burgdorferri, cytomegalovirus, Ebola virus, HSV-1, HERV-W, HIV-1, Epstein-Barr, hepatitis C, influenza, Chlamydia pneumoniae, Porphyrymonas gingivalis, Helicobacter pylori, Toxoplasma gondii, Trypanosoma cruzi). These interactomes also relate to the AD hippocampal transcriptome and to plaque or tangle proteins. Upregulated AD hippocampal genes match those upregulated by multiple bacteria, viruses, fungi, or protozoa in immunocompetent cells. AD genes are enriched in GWAS datasets reflecting pathogen diversity, suggesting selection for pathogen resistance, as supported by the old age of AD patients, implying resistance to earlier infections. APOE4 is concentrated in regions of high parasitic burden and protects against childhood tropical infections and hepatitis C. Immune/inflammatory gain of function applies to APOE4, CR1, and TREM2 variants. AD genes are also expressed in the blood-brain barrier (BBB), which is disrupted by AD risk factors (age, alcohol, aluminum, concussion, cerebral hypoperfusion, diabetes, homocysteine, hypercholesterolemia, hypertension, obesity, pesticides, pollution, physical inactivity, sleep disruption, smoking) and by pathogens, directly or via olfactory routes to basal-forebrain BBB control centers. The BBB benefits from statins, NSAIDs, estrogen, melatonin, memantine, and the Mediterranean diet. Polymicrobial involvement is supported by upregulation of bacterial, viral, and fungal sensors/defenders in the AD brain, blood, or cerebrospinal fluid. AD serum amyloid-β autoantibodies may attenuate its antimicrobial effects favoring microbial survival and cerebral invasion leading to activation of neurodestructive immune/inflammatory processes, which may also be augmented by age-related immunosenescence. AD may thus respond to antibiotic, antifungal, or antiviral therapy.",,"Carter, Chris J.",J Alzheimers Dis Rep.; 1(1):125-157,,,True
e695e6821ad966d7e370bc12a7ec162b264eff0e,PMC,Polymorphisms in AURKA and AURKB are associated with the survival of triple-negative breast cancer patients treated with taxane-based adjuvant chemotherapy,http://dx.doi.org/10.2147/CMAR.S174735,PMC6159783,30288111,CC BY-NC,"PURPOSE: Triple-negative breast cancer (TNBC) is more than a single disease. Identifying biomarkers to further subdivide TNBC patients with distinct outcome is of great importance. It has been reported that single-nucleotide polymorphisms (SNPs) in Aurora kinase A (AURKA) or Aurora kinase B (AURKB) are associated with the risk and survival of several cancers. But till now, there is no research about these polymorphisms in TNBC patients. MATERIALS AND METHODS: In this study, we investigated the association between polymorphisms in AURKA or AURKB gene and prognosis of TNBC patients treated with taxane-based adjuvant chemotherapy. A total of 273 TNBC patients were enrolled. Haploview 4.2 software was used to identify Tag SNPs. Genotyping was conducted using the MassARRAY MALDI-TOF system. RESULTS: We found that AURKA rs6099128 GG genotype carriers had significantly worse overall survival (OS) than TT+ TG genotype carriers (P = 0.003, HR = 12.499, 95% CI = 2.357–66.298). AURKB rs11651993 TT genotype carriers had better disease-free survival (DFS) than TC + CC genotype carriers (P = 0.018, HR = 1.876, 95% CI = 1.116–3.154). AURKB rs2289590 CC genotype carriers had worse DFS than CA + AA genotype carriers (P = 0.021, HR = 0.536, 95% CI = 0.315–0.912). After subgroup analysis, rs11651993 TC + CC genotype predicted worse DFS in subgroups of age ≤ 50, post-menopausal, grade unknown (UK), tumor size >2 cm, and lymph node negative. Rs2289590 CA + AA genotype could predict favorable DFS in pre-menopausal, grade 3 and lymph node-positive patients. CONCLUSION: We first demonstrated that polymorphisms in AURKA or AURKB gene might predict the OS or DFS of TNBC patients treated with taxane-based adjuvant chemotherapy.",2018 Sep 21,"['Liao, Yuqian', 'Liao, Yulu', 'Li, Jun', 'Li, Junyu', 'Fan, Ying', 'Xu, Binghe']",Cancer Manag Res,,,True
f98ea77d586b02146fe03a209e44a0c1e8883ea5,PMC,Recent Advances Towards the Development of a Potent Antiviral Against the Hepatitis E Virus,http://dx.doi.org/10.14218/JCTH.2018.00005,PMC6160310,30271744,CC BY-NC,"Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. It also causes acute liver failure and acute-on-chronic liver failure in many patients, such as those suffering from other infections/liver injuries or organ transplant/chemotherapy recipients. Despite widespread sporadic and epidemic incidents, there is no specific treatment against HEV, justifying an urgent need for developing a potent antiviral against it. This review summarizes the known antiviral candidates and provides an overview of the potential targets for the development of specific antivirals against HEV.",2018 Sep 28,"['Anang, Saumya', 'Kaushik, Nidhi', 'Surjit, Milan']",J Clin Transl Hepatol,,,True
17da3a159054b31e3da81a51ab9ccc26e18bd266,PMC,Preventing the spread of norovirus-like infections by the airborne route using plasma assisted catalytic technology (PACT),http://dx.doi.org/10.1292/jvms.17-0695,PMC6160878,29709903,CC BY-NC-ND,"Zoonoses are frequently reported, and outbreaks of the highly pathogenic influenza virus, severe acute respiratory syndrome, and Middle East respiratory syndrome have occurred recently, in Africa, the Middle East, and Southeast Asia. Sterilization using a chemical reactor with plasma assisted catalytic technology (PACT) was investigated. Tests were carried out on the feline calicivirus (FCV) vaccine strain F9, which is a surrogate of airborne pathogen human norovirus. Results showed that the PACT device could inactivate FCV, which passed through the plasma chamber. Sterilization rate may be more than 99.99% (below the detection limit). These results indicate that PACT may be an effective mean to inactivate many viruses, including human norovirus, and potentially other airborne, infectious microorganisms.",2018 Sep 30,"['TANAKA, Yoshimoto', 'FUJINO, Kan', 'LARKINS, Gerald Andrew', 'OSAWA, Atsushi', 'HAYASHI, Yuji', 'TAHARAGUCHI, Satoshi']",J Vet Med Sci,,,True
7307753da247144e66cc91b8f48c33e5a9ceff2b,PMC,Immune protection conferred by three commonly used commercial live attenuated vaccines against the prevalent local strains of avian infectious bronchitis virus in southern China,http://dx.doi.org/10.1292/jvms.18-0249,PMC6160892,30022779,CC BY-NC-ND,"Live attenuated vaccines are critical in the control of avian infectious bronchitis. It is necessary to know the protection conferred by commonly used commercial live vaccines. In this study, specific pathogen-free chicks were vaccinated with the commercial live vaccines H120, 4/91 and LDT3-A. Blood samples were collected at weekly intervals for the detection of IBV-specific antibodies and quantification of CD4(+) and CD8(+) T lymphocytes. At 21 days post-inoculation the vaccinated birds were challenged with the IBV prevalent local strains GX-YL5, GX-GL11079 and GX-NN09032, respectively. Trachea and kidney samples were collected at 5 days post-challenge for the detection of the virus. The results showed that the H120 group exhibited medium antibody levels, the lowest percentages of CD4(+), CD8(+) T lymphocytes and the highest viral loads. The 4/91 group showed the lowest antibody levels, but the highest percentages of CD4(+), CD8(+) T lymphocytes and the lowest viral loads. The LDT3-A group showed the highest antibody levels, the medium percentages of CD4(+), CD8(+) T lymphocytes and the medium viral loads. The protection rates of H120, 4/91 and LDT3-A groups were 41.7–58.3%, 75.0–83.7% and 66.7–75.0%, respectively. The present study demonstrated that the vaccines H120, 4/91 and LDT3-A could stimulate the immunized chicks to produce different levels of humoral and cellular immunity to resist the infection of IBV, but couldn’t provide complete protection against the prevalent local strains of IBV in southern China. Also, the vaccine 4/91 offered the best immune protection among the three vaccines.",2018 Sep 18,"['FAN, Wen-Sheng', 'LI, He-Ming', 'HE, Yi-Ning', 'TANG, Ning', 'ZHANG, Li-Hua', 'WANG, Hai-Yong', 'ZHONG, Lian', 'CHEN, Jian-Cai', 'WEI, Tian-Chao', 'HUANG, Teng', 'MO, Mei-Lan', 'WEI, Ping']",J Vet Med Sci,,,True
6b399b83db192f4d005e6950ca0e7b77060500a7,PMC,The current perspectives of dromedary camel stem cells research,http://dx.doi.org/10.1016/j.ijvsm.2018.01.002,PMC6161867,30761317,CC BY-NC-ND,"Camels have cultural value in the Arab society and are considered one of the most important animals in the Arabian Peninsula and arid environments, due to the distinct characteristics of their meat and milk. Moreover, there is a great interest in camel racing and beauty shows. Therefore, treatment of elite animals, increasing the number of camels as well as genetic improvement is an essential demand. Because there are unique camels for milk production, meat, or in racing, the need to propagate genetically superior camels is urgent. Recent biotechnological approaches such as stem cells hold great promise for biomedical research, genetic engineering, and as a model for studying early mammalian developmental biology. Establishment of stem cells lines from camels would tremendously facilitate regenerative medicine for genetically superior camels, permit the gene targeting of the camel genome and the generation of genetically modified animal and be a mean for genome conservation for the elite breeds. In this mini-review, we show the current research, future horizons and potential applications for camel stem cells.",2018 Feb 14,"['Saadeldin, Islam M.', 'Abdel-Aziz Swelum, Ayman', 'Alzahrani, Faisal A.', 'Alowaimer, Abdullah N.']",Int J Vet Sci Med,,,False
11af78fdd83655124c3b5acce4cfb92f0aafe4f6,PMC,Restriction of H1N1 influenza virus infection by selenium nanoparticles loaded with ribavirin via resisting caspase-3 apoptotic pathway,http://dx.doi.org/10.2147/IJN.S177658,PMC6165773,30310281,CC BY-NC,"INTRODUCTION: Ribavirin (RBV) is a broad-spectrum antiviral drug. Selenium nanoparticles (SeNPs) attract much attention in the biomedical field and are used as carriers of drugs in current research studies. In this study, SeNPs were decorated by RBV, and the novel nanoparticle system was well characterized. Madin-Darby Canine Kidney cells were infected with H1N1 influenza virus before treatment with RBV, SeNPs, and SeNPs loaded with RBV (Se@RBV). METHODS AND RESULTS: MTT assay showed that Se@RBV nanoparticles protect cells during H1N1 infection in vitro. Se@RBV depressed virus titer in the culture supernatant. Intracellular localization detection revealed that Se@RBV accumulated in lysosome and escaped to cytoplasm as time elapsed. Furthermore, activation of caspase-3 was resisted by Se@RBV. Expressions of proteins related to caspase-3, including cleaved poly-ADP-ribose polymerase, caspase-8, and Bax, were downregulated evidently after treatment with Se@RBV compared with the untreated infection group. In addition, phosphorylations of phosphorylated 38 (p38), JNK, and phosphorylated 53 (p53) were inhibited as well. In vivo experiments indicated that Se@RBV was found to prevent lung injury in H1N1-infected mice through hematoxylin and eosin staining. Tunel test of lung tissues present that DNA damage reached a high level but reduced substantially when treated with Se@RBV. Immunohistochemical test revealed an identical result with the in vitro experiment that activations of caspase-3 and proteins on the apoptosis pathway were restrained by Se@RBV treatment. CONCLUSION: Taken together, this study elaborates that Se@RBV is a novel promising agent against H1N1 influenza virus infection.",2018 Sep 26,"['Lin, Zhengfang', 'Li, Yinghua', 'Gong, Guifang', 'Xia, Yu', 'Wang, Changbing', 'Chen, Yi', 'Hua, Liang', 'Zhong, Jiayu', 'Tang, Ying', 'Liu, Xiaomin', 'Zhu, Bing']",Int J Nanomedicine,,,True
829ce386c84e17559ca6a06ee9aee0475e473343,PMC,Viruses causing lower respiratory symptoms in young children: findings from the ORChID birth cohort,http://dx.doi.org/10.1136/thoraxjnl-2017-210233,PMC6166599,29247051,CC BY-NC,"INTRODUCTION: Viral acute respiratory infections (ARIs) cause substantial child morbidity. Sensitive molecular-based assays aid virus detection, but the clinical significance of positive tests remains uncertain as some viruses may be found in both acutely ill and healthy children. We describe disease-pathogen associations of respiratory viruses and quantify virus-specific attributable risk of ARIs in healthy children during the first 2 years of life. METHODS: One hundred fifty-eight term newborn babies in Brisbane, Australia, were recruited progressively into a longitudinal, community-based, birth cohort study conducted between September 2010 and October 2014. A daily tick-box diary captured predefined respiratory symptoms from birth until their second birthday. Weekly parent-collected nasal swabs were batch-tested for 17 respiratory viruses by PCR assays, allowing calculation of virus-specific attributable fractions in the exposed (AFE) to determine the proportion of virus-positive children whose ARI symptoms could be attributed to that particular virus. RESULTS: Of 8100 nasal swabs analysed, 2646 (32.7%) were virus-positive (275 virus codetections, 3.4%), with human rhinoviruses accounting for 2058/2646 (77.8%) positive swabs. Viruses were detected in 1154/1530 (75.4%) ARI episodes and in 984/4308 (22.8%) swabs from asymptomatic periods. Respiratory syncytial virus (AFE: 68% (95% CI 45% to 82%)) and human metapneumovirus (AFE: 69% (95% CI 43% to 83%)) were strongly associated with higher risk of lower respiratory symptoms. DISCUSSION: The strong association of respiratory syncytial virus and human metapneumovirus with ARIs and lower respiratory symptoms in young children managed within the community indicates successful development of vaccines against these two viruses should provide substantial health benefits.",2018 Oct 15,"['Sarna, Mohinder', 'Lambert, Stephen B', 'Sloots, Theo P', 'Whiley, David M', 'Alsaleh, Asma', 'Mhango, Lebogang', 'Bialasiewicz, Seweryn', 'Wang, David', 'Nissen, Michael D', 'Grimwood, Keith', 'Ware, Robert S']",Thorax,,,True
7b9f9339ac1f541b560e1c3c0ce6697cb8c8cc3b,PMC,Viruses causing lower respiratory symptoms in young children: findings from the ORChID birth cohort,http://dx.doi.org/10.1136/thoraxjnl-2017-210233,PMC6166599,29247051,CC BY-NC,"INTRODUCTION: Viral acute respiratory infections (ARIs) cause substantial child morbidity. Sensitive molecular-based assays aid virus detection, but the clinical significance of positive tests remains uncertain as some viruses may be found in both acutely ill and healthy children. We describe disease-pathogen associations of respiratory viruses and quantify virus-specific attributable risk of ARIs in healthy children during the first 2 years of life. METHODS: One hundred fifty-eight term newborn babies in Brisbane, Australia, were recruited progressively into a longitudinal, community-based, birth cohort study conducted between September 2010 and October 2014. A daily tick-box diary captured predefined respiratory symptoms from birth until their second birthday. Weekly parent-collected nasal swabs were batch-tested for 17 respiratory viruses by PCR assays, allowing calculation of virus-specific attributable fractions in the exposed (AFE) to determine the proportion of virus-positive children whose ARI symptoms could be attributed to that particular virus. RESULTS: Of 8100 nasal swabs analysed, 2646 (32.7%) were virus-positive (275 virus codetections, 3.4%), with human rhinoviruses accounting for 2058/2646 (77.8%) positive swabs. Viruses were detected in 1154/1530 (75.4%) ARI episodes and in 984/4308 (22.8%) swabs from asymptomatic periods. Respiratory syncytial virus (AFE: 68% (95% CI 45% to 82%)) and human metapneumovirus (AFE: 69% (95% CI 43% to 83%)) were strongly associated with higher risk of lower respiratory symptoms. DISCUSSION: The strong association of respiratory syncytial virus and human metapneumovirus with ARIs and lower respiratory symptoms in young children managed within the community indicates successful development of vaccines against these two viruses should provide substantial health benefits.",2018 Oct 15,"['Sarna, Mohinder', 'Lambert, Stephen B', 'Sloots, Theo P', 'Whiley, David M', 'Alsaleh, Asma', 'Mhango, Lebogang', 'Bialasiewicz, Seweryn', 'Wang, David', 'Nissen, Michael D', 'Grimwood, Keith', 'Ware, Robert S']",Thorax,,,True
5ab92ddf1bb39b6863b28e2e9946415f7a5adf34,PMC,A survey on infection control in emergency departments in Japan,http://dx.doi.org/10.1002/ams2.360,PMC6167398,30338085,CC BY-NC,"AIM: Infection control in the emergency department is important for hospital risk management; however, few clinical guidelines have been established. This study aimed to determine whether hospitals in Japan have infection control manuals, and investigate the contents of manuals, consulting systems, and isolation facilities for emergency departments. METHODS: A total of 517 hospitals certified as educational institutions for board‐certified acute care physicians in Japan were requested between March and May 2015 to provide a written evaluation of the infection control in the emergency department. RESULTS: A total of 51 of 303 (16.8%) hospitals had no manuals regarding infection control in the emergency department. Among 250 hospitals having emergency department manuals, 115 (46.0%) did not include contents regarding disinfection and sterilization for imaging examination rooms, and only 44 (17.6%) had criteria for contacting the emergency medical service when patients are suspected of, or diagnosed with, communicable diseases. Of the 303 hospitals, 277 (91.4%) prepared specific manuals for the 2009 pandemic influenza. Of the 303 hospitals, 80 (26.4%) did not prepare manuals for the Ebola virus disease outbreak in West Africa in 2014. Furthermore, 92 (30.4%) of the 303 hospitals did not have any negative‐pressure isolation rooms. CONCLUSIONS: Practices and guidelines necessary for infection control in the emergency department were not sufficiently covered in the hospitals studied. Education, information sharing, and a checklist for preparing manuals are needed to establish better infection control systems in emergency departments.",2018 Jul 30,"['Kudo, Daisuke', 'Sasaki, Junichi', 'Ikeda, Hiroto', 'Shiino, Yasukazu', 'Shime, Nobuaki', 'Mochizuki, Toru', 'Morita, Masanori', 'Soeda, Hiroshi', 'Ohge, Hiroki', 'Lee, Jong Ja', 'Fujita, Masahisa', 'Miyairi, Isao', 'Kato, Yasuyuki', 'Watanabe, Manabu', 'Yokota, Hiroyuki', None]",Acute Med Surg,,,True
7a3b1df462ac5224e195a12287ee156064910bf0,PMC,A planetary vision for one health,http://dx.doi.org/10.1136/bmjgh-2018-001137,PMC6169660,30294465,CC BY-NC,,2018 Oct 2,"['Rabinowitz, Peter MacGarr', 'Pappaioanou, Marguerite', 'Bardosh, Kevin Louis', 'Conti, Lisa']",BMJ Glob Health,,,True
751591a95a9673f692d3a0189ca5a9b0c7e8781c,PMC,Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency,http://dx.doi.org/10.1084/jem.20180628,PMC6170168,30143481,CC BY-NC-SA,"Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5-yr-old child with severe pulmonary influenza at 2 yr. She is homozygous for a loss-of-function IRF9 allele. Her cells activate gamma-activated factor (GAF) STAT1 homodimers but not IFN-stimulated gene factor 3 (ISGF3) trimers (STAT1/STAT2/IRF9) in response to IFN-α2b. The transcriptome induced by IFN-α2b in the patient’s cells is much narrower than that of control cells; however, induction of a subset of IFN-stimulated gene transcripts remains detectable. In vitro, the patient’s cells do not control three respiratory viruses, influenza A virus (IAV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV). These phenotypes are rescued by wild-type IRF9, whereas silencing IRF9 expression in control cells increases viral replication. However, the child has controlled various common viruses in vivo, including respiratory viruses other than IAV. Our findings show that human IRF9- and ISGF3-dependent type I and III IFN responsive pathways are essential for controlling IAV.",2018 Oct 1,"['Hernandez, Nicholas', 'Melki, Isabelle', 'Jing, Huie', 'Habib, Tanwir', 'Huang, Susie S.Y.', 'Danielson, Jeffrey', 'Kula, Tomasz', 'Drutman, Scott', 'Belkaya, Serkan', 'Rattina, Vimel', 'Lorenzo-Diaz, Lazaro', 'Boulai, Anais', 'Rose, Yoann', 'Kitabayashi, Naoki', 'Rodero, Mathieu P.', 'Dumaine, Cecile', 'Blanche, Stéphane', 'Lebras, Marie-Noëlle', 'Leung, Man Chun', 'Mathew, Lisa Sara', 'Boisson, Bertrand', 'Zhang, Shen-Ying', 'Boisson-Dupuis, Stephanie', 'Giliani, Silvia', 'Chaussabel, Damien', 'Notarangelo, Luigi D.', 'Elledge, Stephen J.', 'Ciancanelli, Michael J.', 'Abel, Laurent', 'Zhang, Qian', 'Marr, Nico', 'Crow, Yanick J.', 'Su, Helen C.', 'Casanova, Jean-Laurent']",J Exp Med,,,True
fa994c4585ad68547b8a9fd973109d183fe8b71e,PMC,Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency,http://dx.doi.org/10.1084/jem.20180628,PMC6170168,30143481,CC BY-NC-SA,"Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5-yr-old child with severe pulmonary influenza at 2 yr. She is homozygous for a loss-of-function IRF9 allele. Her cells activate gamma-activated factor (GAF) STAT1 homodimers but not IFN-stimulated gene factor 3 (ISGF3) trimers (STAT1/STAT2/IRF9) in response to IFN-α2b. The transcriptome induced by IFN-α2b in the patient’s cells is much narrower than that of control cells; however, induction of a subset of IFN-stimulated gene transcripts remains detectable. In vitro, the patient’s cells do not control three respiratory viruses, influenza A virus (IAV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV). These phenotypes are rescued by wild-type IRF9, whereas silencing IRF9 expression in control cells increases viral replication. However, the child has controlled various common viruses in vivo, including respiratory viruses other than IAV. Our findings show that human IRF9- and ISGF3-dependent type I and III IFN responsive pathways are essential for controlling IAV.",2018 Oct 1,"['Hernandez, Nicholas', 'Melki, Isabelle', 'Jing, Huie', 'Habib, Tanwir', 'Huang, Susie S.Y.', 'Danielson, Jeffrey', 'Kula, Tomasz', 'Drutman, Scott', 'Belkaya, Serkan', 'Rattina, Vimel', 'Lorenzo-Diaz, Lazaro', 'Boulai, Anais', 'Rose, Yoann', 'Kitabayashi, Naoki', 'Rodero, Mathieu P.', 'Dumaine, Cecile', 'Blanche, Stéphane', 'Lebras, Marie-Noëlle', 'Leung, Man Chun', 'Mathew, Lisa Sara', 'Boisson, Bertrand', 'Zhang, Shen-Ying', 'Boisson-Dupuis, Stephanie', 'Giliani, Silvia', 'Chaussabel, Damien', 'Notarangelo, Luigi D.', 'Elledge, Stephen J.', 'Ciancanelli, Michael J.', 'Abel, Laurent', 'Zhang, Qian', 'Marr, Nico', 'Crow, Yanick J.', 'Su, Helen C.', 'Casanova, Jean-Laurent']",J Exp Med,,,True
a2d7c5fc05284d7176ae30fd6fe4967cdc111f10,PMC,"Characterization of the structure, cells, and cellular mechanobiological response of human plantar fascia",http://dx.doi.org/10.1177/2041731418801103,PMC6170959,30302189,CC BY-NC,"In this study, we report that human plantar fascia consists of two distinct tissues with differential structural properties. These tissues also contain stem/progenitor cells with differential biological properties. The mechanobiological responses of these two plantar fascia stem cells also differ in terms of expression of collagen I and IV, non-ligament-related genes, and proinflammatory genes. The production of inflammatory agents (prostaglandin E(2), interleukin-6) and matrix degradative enzymes (matrix metalloproteinase-1, matrix metalloproteinase-2) are also different between the two types of plantar fascia stem cells. Based on the findings from this study, we suggest that plantar fasciitis results from the aberrant mechanobiological responses of the stem cells from plantar fascia sheath and core tissues. Our findings may also be used to devise tissue engineering approaches to treat plantar fascia injury effectively.",2018 Oct 3,"['Zhang, Jianying', 'Nie, Daibang', 'Rocha, Jorge L', 'Hogan, MaCalus V', 'Wang, James H-C']",J Tissue Eng,,,True
138e18baf12e4e92b67ab7dee321d2b149f236ed,PMC,"The changes of prevalence and etiology of pediatric pneumonia from National Emergency Department Information System in Korea, between 2007 and 2014",http://dx.doi.org/10.3345/kjp.2017.06100,PMC6172518,30274507,CC BY-NC,"PURPOSE: Understanding changes in pathogen and pneumonia prevalence among pediatric pneumonia patients is important for the prevention of infectious diseases. METHODS: We retrospectively analyzed data of children younger than 18 years diagnosed with pneumonia at 117 Emergency Departments in Korea between 2007 and 2014. RESULTS: Over the study period, 329,380 pediatric cases of pneumonia were identified. The most frequent age group was 1–3 years old (48.6%) and the next was less than 12 months of age (17.4%). Based on International Classification of Diseases, 10th revision diagnostic codes, confirmed cases of viral pneumonia comprised 8.4% of all cases, pneumonia due to Mycoplasma pneumoniae comprised 3.8% and confirmed cases of bacterial pneumonia 1.3%. The prevalence of confirmed bacterial pneumonia decreased from 3.07% in 2007 and 4.01% in 2008 to 0.65% in 2014. The yearly rate of pneumococcal pneumonia also decreased from 0.47% in 2007 to 0.08% in 2014. A periodic prevalence of M. pneumoniae pneumonia (MP) was identified. CONCLUSION: The increased number of patients with pneumonia, bacterial pneumonia, pleural effusion, and empyema in 2011 and 2013–2014 resulted from an MP epidemic. We provide evidence that the frequency of confirmed cases of bacterial pneumonia and pneumococcal pneumonia has declined from 2007 to 2014, which can simultaneously reflect the effectiveness of the pneumococcal conjugate vaccine.",2018 Sep 15,"['Shin, Eun Ju', 'Kim, Yunsun', 'Jeong, Jin-Young', 'Jung, Yu Mi', 'Lee, Mi-Hee', 'Chung, Eun Hee']",Korean J Pediatr,,,True
43fb44b6c809c497fa4e6e7a52e7a3dbbebe4155,PMC,Microbiological testing of adults hospitalised with community-acquired pneumonia: an international study,http://dx.doi.org/10.1183/23120541.00096-2018,PMC6174282,30474036,CC BY-NC,"This study aimed to describe real-life microbiological testing of adults hospitalised with community-acquired pneumonia (CAP) and to assess concordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) and 2011 European Respiratory Society (ERS) CAP guidelines. This was a cohort study based on the Global Initiative for Methicillin-resistant Staphylococcus aureus Pneumonia (GLIMP) database, which contains point-prevalence data on adults hospitalised with CAP across 54 countries during 2015. In total, 3702 patients were included. Testing was performed in 3217 patients, and included blood culture (71.1%), sputum culture (61.8%), Legionella urinary antigen test (30.1%), pneumococcal urinary antigen test (30.0%), viral testing (14.9%), acute-phase serology (8.8%), bronchoalveolar lavage culture (8.4%) and pleural fluid culture (3.2%). A pathogen was detected in 1173 (36.5%) patients. Testing attitudes varied significantly according to geography and disease severity. Testing was concordant with IDSA/ATS and ERS guidelines in 16.7% and 23.9% of patients, respectively. IDSA/ATS concordance was higher in Europe than in North America (21.5% versus 9.8%; p<0.01), while ERS concordance was higher in North America than in Europe (33.5% versus 19.5%; p<0.01). Testing practices of adults hospitalised with CAP varied significantly by geography and disease severity. There was a wide discordance between real-life testing practices and IDSA/ATS/ERS guideline recommendations.",2018 Oct 8,"['Carugati, Manuela', 'Aliberti, Stefano', 'Reyes, Luis Felipe', 'Franco Sadud, Ricardo', 'Irfan, Muhammad', 'Prat, Cristina', 'Soni, Nilam J.', 'Faverio, Paola', 'Gori, Andrea', 'Blasi, Francesco', 'Restrepo, Marcos I.']",ERJ Open Res,,,True
4aa64b68fec8e053f6abcc1594eee14507853618,PMC,Designing of CD8(+) and CD8(+)-overlapped CD4(+) epitope vaccine by targeting late and early proteins of human papillomavirus,http://dx.doi.org/10.2147/BTT.S177901,PMC6174296,30323556,CC BY-NC,"BACKGROUND AND AIM: Human papillomavirus (HPV) is an oncogenic agent that causes over 90% of cases of cervical cancer in the world. Currently available prophylactic vaccines are type specific and have less therapeutic efficiency. Therefore, we aimed to predict the potential species-specific and therapeutic epitopes from the protein sequences of HPV45 by using different immunoinformatics tools. METHODS: Initially, we determined the antigenic potential of late (L1 and L2) and early (E1, E2, E4, E5, E6, and E7) proteins. Then, major histocompatibility complex class I-restricted CD8(+) T-cell epitopes were selected based on their immunogenicity. In addition, epitope conservancy, population coverage (PC), and target receptor-binding affinity of the immunogenic epitopes were determined. Moreover, we predicted the possible CD8(+), nested interferon gamma (IFN-γ)-producing CD4(+), and linear B-cell epitopes. Further, antigenicity, allergenicity, immunogenicity, and system biology-based virtual pathway associated with cervical cancer were predicted to confirm the therapeutic efficiency of overlapped epitopes. RESULTS: Twenty-seven immunogenic epitopes were found to exhibit cross-protection (≥55%) against the 15 high-risk HPV strains (16, 18, 31, 33, 35, 39, 51, 52, 56, 58, 59, 68, 69, 73, and 82). The highest PC was observed in Europe (96.30%), North America (93.98%), West Indies (90.34%), North Africa (90.14%), and East Asia (89.47%). Binding affinities of 79 docked complexes observed as global energy ranged from −10.80 to −86.71 kcal/mol. In addition, CD8(+) epitope-overlapped segments in CD4(+) and B-cell epitopes demonstrated that immunogenicity and IFN-γ-producing efficiency ranged from 0.0483 to 0.5941 and 0.046 to 18, respectively. Further, time core simulation revealed the overlapped epitopes involved in pRb, p53, COX-2, NF-X1, and HPV45 infection signaling pathways. CONCLUSION: Even though the results of this study need to be confirmed by further experimental peptide sensitization studies, the findings on immunogenic and IFN-γ-producing CD8(+) and overlapped epitopes provide new insights into HPV vaccine development.",2018 Oct 2,"['Kaliamurthi, Satyavani', 'Selvaraj, Gurudeeban', 'Kaushik, Aman Chandra', 'Gu, Ke-Ren', 'Wei, Dong-Qing']",Biologics,,,True
26cb41132d945aa5cff35a80761daf086a4375e0,PMC,Pseudomonas aeruginosa infection increases the readmission rate of COPD patients,http://dx.doi.org/10.2147/COPD.S173759,PMC6174684,30323578,CC BY-NC,"INTRODUCTION: Acute exacerbation of COPD (AECOPD) leads to rapid deterioration of pulmonary function and quality of life. It is unclear whether the prognosis for AECOPD differs depending on the bacterium or virus identified. The purpose of this study is to determine whether readmission of patients with severe AECOPD varies according to the bacterium or virus identified. METHODS: We performed a retrospective review of medical records of 704 severe AECOPD events at Korea University Guro Hospital from January 2011 to May 2017. We divided events into two groups, one in which patients were readmitted within 30 days after discharge and the other in which there was no readmission. RESULTS: Of the 704 events, 65 were followed by readmission within 30 days. Before propensity score matching, the readmission group showed a higher rate of bacterial identification with no viral identification and a higher rate of identification with the Pseudomonas aeruginosa (P=0.003 and P=0.007, respectively). Using propensity score matching, the readmission group still showed a higher P. aeruginosa identification rate (P=0.030), but there was no significant difference in the rate of bacterial identification, with no viral identification (P=0.210). In multivariate analysis, the readmission group showed a higher P. aeruginosa identification rate than the no-readmission group (odds ratio, 4.749; 95% confidence interval, 1.296–17.041; P=0.019). CONCLUSION: P. aeruginosa identification is associated with a higher readmission rate in AECOPD patients.",2018 Oct 2,"['Choi, Juwhan', 'Oh, Jee Youn', 'Lee, Young Seok', 'Hur, Gyu Young', 'Lee, Sung Yong', 'Shim, Jae Jeong', 'Kang, Kyung Ho', 'Min, Kyung Hoon']",Int J Chron Obstruct Pulmon Dis,,,True
eb979bab57933dd9c6c1c02684bd3d7002cb604c,PMC,Identification of enteric viruses circulating in a dog population with low vaccine coverage,http://dx.doi.org/10.1016/j.bjm.2018.02.006,PMC6175709,29588198,CC BY-NC-ND,"Although the use of vaccines has controlled enteric diseases in dogs in many developed countries, vaccine coverage is still under optimal situation in Brazil. There is a large population of nonimmunized dogs and few studies about the identification of the viruses associated with diarrhea. To address this situation, stool samples from 325 dogs were analyzed by polymerase chain reaction for the detection of common enteric viruses such as Canine adenovirus (CAdV), Canine coronavirus (CCoV), Canine distemper virus (CDV), Canine rotavirus (CRV) and Carnivorous protoparvovirus 1 (canine parvovirus 2; CPV-2). At least one of these species was detected in 56.6% (184/325) of the samples. The viruses detected most frequently in either diarrheic or nondiarrheic dog feces were CPV-2 (54.3% of the positive samples), CDV (45.1%) and CCoV (30.4%), followed by CRV (8.2%) and CAdV (4.9%). Only one agent was detected in the majority of the positive samples (63%), but co-infections were present in 37% of the positive samples and mainly included CDV and CPV-2. The data presented herein can improve the clinical knowledge in regions with low vaccine coverage and highlight the need to improve the methods used to control these infectious diseases in domestic dogs.",2018 Mar 15,"['Alves, Christian D.B.T.', 'Granados, Oscar F.O.', 'Budaszewski, Renata da F.', 'Streck, André F.', 'Weber, Matheus N.', 'Cibulski, Samuel P.', 'Pinto, Luciane D.', 'Ikuta, Nilo', 'Canal, Cláudio W.']",Braz J Microbiol,,,False
2060cb027399ce2ff97b6f9d17b932aa16dd0844,PMC,Montelukast Reduces Serum Levels of Eosinophil-Derived Neurotoxin in Preschool Asthma,http://dx.doi.org/10.4168/aair.2018.10.6.686,PMC6182197,30306750,CC BY-NC,"PURPOSE: Several markers for eosinophilic inflammation have been proposed to predict response to asthma treatment. However, definitive criteria for treatment decisions have not yet been established. We investigate a potentially useful relatively non-invasive biomarker, eosinophil-derived neurotoxin (EDN), to predict favorable responses to budesonide or montelukast, common treatment for children with asthma. METHODS: Young children (1 to 6 years old) were enrolled in this randomized, parallel, 2-group, open-label trial. Criteria for eligibility included: 1) being symptomatic during the run-in period; and 2) having a serum EDN (sEDN) level ≥ 53 ng/mL, with positive specific immunoglobulin E to house dust mite. Eligible patients were randomly placed into 2 groups: the BIS group received budesonide inhalation suspension (BIS) 0.5 mg once daily; the MONT group received montelukast 4 mg once daily. Ineligible patients were invited to receive montelukast 4 mg once daily (OBS group). Treatment period was 12 weeks. RESULTS: Asthma control days increased significantly in the BIS and MONT groups (P < 0.000) over the 12-week study period. There was no significant change in sEDN in the BIS group but there was a significant decrease in the MONT group (P < 0.000). Patients in the OBS group with high EDN levels (< 53 ng/mL) showed a significant decrease due to MONT treatment (P = 0.023). Rescue medication usage significantly decreased in the BIS and MONT groups (P < 0.000). CONCLUSIONS: EDN is a useful relatively non-invasive biomarker for predicting responses to montelukast and budesonide treatment of preschool children with beta2-agonist responsive recurrent wheeze and multiple-trigger wheeze (Trial registry at UMIN Clinical Trials Registry, UMIN000008335).",2018 Nov 30,"['Kim, Chang-Keun', 'Callaway, Zak', 'Park, Jin-Sung', 'Nishimori, Hisashi', 'Ogino, Tikatoshi', 'Nagao, Mizuho', 'Fujisawa, Takao']",Allergy Asthma Immunol Res,,,True
6bdb41aa63efed5063efbecbb615896b8ea4ae5e,PMC,A Simple Method to Detect Candidate Overlapping Genes in Viruses Using Single Genome Sequences,http://dx.doi.org/10.1093/molbev/msy155,PMC6188560,30099499,CC BY-NC,"Overlapping genes in viruses maximize the coding capacity of their genomes and allow the generation of new genes without major increases in genome size. Despite their importance, the evolution and function of overlapping genes are often not well understood, in part due to difficulties in their detection. In addition, most bioinformatic approaches for the detection of overlapping genes require the comparison of multiple genome sequences that may not be available in metagenomic surveys of virus biodiversity. We introduce a simple new method for identifying candidate functional overlapping genes using single virus genome sequences. Our method uses randomization tests to estimate the expected length of open reading frames and then identifies overlapping open reading frames that significantly exceed this length and are thus predicted to be functional. We applied this method to 2548 reference RNA virus genomes and find that it has both high sensitivity and low false discovery for genes that overlap by at least 50 nucleotides. Notably, this analysis provided evidence for 29 previously undiscovered functional overlapping genes, some of which are coded in the antisense direction suggesting there are limitations in our current understanding of RNA virus replication.",2018 Oct 7,"['Schlub, Timothy E', 'Buchmann, Jan P', 'Holmes, Edward C']",Mol Biol Evol,,,True
626bcea8ab6811ee19f946cb84a273601cfd7bcc,PMC,Challenges in identifying antibiotic resistance targets for point-of-care diagnostics in general practice,http://dx.doi.org/10.2217/fmb-2018-0084,PMC6190172,30113214,CC BY-NC-ND,"General practitioners stand at the front line of healthcare provision and have a pivotal role in the fight against increasing antibiotic resistance. In this respect, targeted antibiotic prescribing by general practitioners would help reduce the unnecessary use of antibiotics, leading to reduced treatment failures, fewer side-effects for patients and a reduction in the (global) spread of antibiotic resistances. Current ‘gold standard’ antibiotic resistance detection strategies tend to be slow, taking up to 48 h to obtain a result, although the implementation of point-of-care testing by general practitioners could help achieve the goal of targeted antibiotic prescribing practices. However, deciding on which antibiotic resistances to include in a point-of-care diagnostic is not a trivial task, as outlined in this publication.",2018 Aug 16,"['Mitsakakis, Konstantinos', 'Kaman, Wendy E', 'Elshout, Gijs', 'Specht, Mara', 'Hays, John P']",Future Microbiol,,,True
41199e837e1c706b7a8a1a8a0970856974235566,PMC,Protective Effect and Mechanism of Alprostadil in Acute Respiratory Distress Syndrome Induced by Oleic Acid in Rats,http://dx.doi.org/10.12659/MSM.909678,PMC6190919,30296789,CC BY-NC-ND,"BACKGROUND: This study investigated the role and mechanism of alprostadil in acute respiratory distress syndrome (ARDS) induced by oleic acid (OA) in rats. MATERIAL/METHODS: Sprague-Dawley rats were randomly divided into control, OA model, and OA + Alprostadil (2.5, 5, and 10 μg/kg, respectively) groups. The ARDS model was induced by femoral vein injection of OA, and alprostadil was administrated immediately. Lung injury was evaluated by lung wet-dry weight ratio (W/D) and histological analyses. Expressions of ACE, inflammatory mediators, apoptotic-related proteins, and proteins in the MAPKs and NF-κB signaling pathways were determined by Western blot or immunohistochemical staining. RESULTS: Compared with the control group, the OA model group had significantly increased W/D, lung injury score, and collagen deposition at 3 h after OA injection. However, alprostadil (10 μg/kg) treatment significantly reduced OA-induced elevation of these indicators. Additionally, OA-induced expression of TNF-α and IL-1β were suppressed by alprostadil. The OA-induced activation of nuclear factor (NF) κB p65 was also reduced by alprostadil. Furthermore, we found that Alprostadil had an inhibitory effect on the phosphorylation of JNK, ERK1/2, and p38 MAPKs. Alprostadil inhibited Bax but increased Bcl-2, indicating a suppressive role in apoptosis. Remarkably increased expression of ACE in the OA model group was observed, which was decreased by alprostadil. CONCLUSIONS: Alprostadil has a protective effect on ARDS induced by OA in rats, possibly through inhibiting apoptosis, suppressing the activation of MAPKs and NF-κB signaling pathways, and decreasing ACE protein expression. Therefore, the use of alprostadil in clinical ARDS treatment is promising.",2018 Oct 8,"['Yan, Xiujuan', 'Li, Yingxiu', 'Choi, Yun Ho', 'Wang, Chongyang', 'Piao, Yihua', 'Ye, Jing', 'Jiang, Jingzhi', 'Li, Liangchang', 'Xu, Huixian', 'Cui, Qingsong', 'Yan, Guanghai', 'Jin, Minggen']",Med Sci Monit,,,True
904d886a8a305e2bc1125fccad82741d78690fef,PMC,"Therapeutic Efficacy and Safety of Prolonged Macrolide, Corticosteroid, Doxycycline, and Levofloxacin against Macrolide-Unresponsive Mycoplasma pneumoniae Pneumonia in Children",http://dx.doi.org/10.3346/jkms.2018.33.e268,PMC6193889,30344461,CC BY-NC,"BACKGROUND: We aimed to compare the therapeutic efficacy of prolonged macrolide (PMC), corticosteroids (CST), doxycycline (DXC), and levofloxacin (LFX) against macrolide-unresponsive Mycoplasma pneumoniae (MP) pneumonia in children and to evaluate the safety of the secondary treatment agents. METHODS: We retrospectively analyzed the data of patients with MP pneumonia hospitalized between January 2015 and April 2017. Macrolide-unresponsiveness was clinically defined with a persistent fever of ≥ 38.0°C at ≥ 72 hours after macrolide treatment. The cases were divided into four groups: PMC, CST, DXC, and LFX. We compared the time to defervescence (TTD) after secondary treatment and the TTD after initial macrolide treatment in each group with adjustment using propensity score-matching analysis. RESULTS: Among 1,165 cases of MP pneumonia, 190 (16.3%) were unresponsive to macrolides. The proportion of patients who achieved defervescence within 48 hours in CST, DXC, and LFX groups were 96.9% (31/33), 85.7% (12/14), and 83.3% (5/6), respectively. The TTD after initial macrolide treatment did not differ between PMC and CST groups (5.1 vs. 4.2 days, P = 0.085), PMC and DXC groups (4.9 vs. 5.7 days, P = 0.453), and PMC and LFX groups (4.4 vs. 5.0 days, P = 0.283). No side effects were observed in the CST, DXC, and LFX groups. CONCLUSION: The change to secondary treatment did not show better efficacy compared to PMC in children with macrolide-unresponsive MP pneumonia. Further studies are needed to guide appropriate treatment in children with MP pneumonia.",2018 Sep 18,"['Ha, Seok Gyun', 'Oh, Kyung Jin', 'Ko, Kwang-Pil', 'Sun, Yong Han', 'Ryoo, Eell', 'Tchah, Hann', 'Jeon, In Sang', 'Kim, Hyo Jeong', 'Ahn, Jung Min', 'Cho, Hye-Kyung']",J Korean Med Sci,,,True
0a098b3876e799d9b21608e26e80d05aa9ec6475,PMC,"Undernutrition, obesity and governance: a unified framework for upholding the right to food",http://dx.doi.org/10.1136/bmjgh-2018-000886,PMC6195135,30364379,CC BY-NC,"This paper addresses the need for conceptual and analytic clarity on nutrition governance, an essential underpinning of more effective approaches for undernutrition, the ‘single greatest constraint to global development’ and obesity, which already accounts for 4% of the world’s disease burden and is growing rapidly. The governance of nutrition, which is essential to designing and implementing policies to realise the right to food, is among the most important and most defining duties of society. But research and action on nutrition governance are hampered by the absence of conceptual rigour, even as the continuing very high burden of undernutrition and the rapid rise in obesity highlight the need for such structures. The breadth of nutrition itself suggests that governance is both needed and sure to be complicated. This analysis explores the reasons attention has come to governance in development policy making, and why it has focused on nutrition governance in particular. It then assesses how the concept of nutrition governance has been used, finding that it has become increasingly prominent in scholarship on poor nutritional outcomes, but remains weakly specified and is invoked by different authors to mean different things. Undernutrition analysts have stressed coordination problems and structural issues related to the general functioning of government. Those studying obesity have emphasised international trade policies, regulatory issues and corporate behaviour. This paper argues that the lack of a clear, operational definition of governance is a serious obstacle to conceptualising and solving major problems in nutrition. To address this need, it develops a unified definition of nutrition governance consisting of three principles: accountability, participation and responsiveness. These are justified with reference to the social contract that defines modern nations and identifies citizens as the ultimate source of national power and legitimacy. A unified framework is then employed to explore solutions to nutrition governance problems.",2018 Oct 10,"Bump, Jesse B",BMJ Glob Health,,,True
6005b8055730f4625c1995a57def5c32fa3f4ec7,PMC,Tuberculosis-associated Immune Thrombocytopenia: A Case Report,http://dx.doi.org/10.4103/sjmms.sjmms_140_16,PMC6196693,30787844,CC BY-NC-SA,"Various hematological manifestations are known to occur with tuberculosis (TB), but its association with immune thrombocytopenia is uncommon and not well recognized. Here, the case of a 39-year-old male who presented with a history of epistaxis and hematuria is described. The patient was found to have diffuse lymphadenopathy both clinically and radiologically. He was diagnosed with immune thrombocytopenia; however, there was a delay in the diagnosis of TB because of the patient's refusal of lymph node biopsy and late recognition of the association between TB and immune thrombocytopenia. Treatment with steroids without antituberculosis medications may have led to reactivation and dissemination of tuberculous infection in this patient. Later, the patient was readmitted with a suspected community-acquired pneumonia and the sputum smear was positive for acid-fast bacilli. Unfortunately, the patient died after he developed sepsis and multiorgan failure. The purpose of this case report is to highlight this rare combination and create awareness among clinicians to consider TB as an underlying etiology of immune thrombocytopenia, especially if there are other associated physical findings such as the presence of lymphadenopathy.",2018 Aug 14 Sep-Dec,"['Al Argan, Reem J.', 'Al Elq, Abdulmohsen H.']",Saudi J Med Med Sci,,,True
616cdd0a8b488fcf0b28781f710cc7fba8625a4d,PMC,"Molecular detection and phylogenetic properties of isolated infectious bronchitis viruses from broilers in Ahvaz, southwest Iran, based on partial sequences of spike gene",http://dx.doi.org/10.30466/vrf.2018.32089,PMC6198162,30357063,CC BY-NC,"Infectious bronchitis (IB) is a highly contagious disease involving mostly upper respiratory tract in chickens, leading to significant economic losses in the poultry industry worldwide. One of the major concerns regarding to IB is the emergence of new types of infectious bronchitis viruses (IBVs). The purpose of this study was to identify the IBVs isolated from Iranian broiler chickens with respiratory symptoms. Twenty-five broiler flocks around Ahwaz (southwest of Iran) were examined for IBV. The specimens including trachea, lung, liver, kidney, and ceacal tonsil, were collected from diseased birds and inoculated into chicken embryonated eggs. Harvested allantoic fluids were subjected to reverse transcription polymerase chain reaction (RT-PCR) using primers in order to amplify spike 1 (S1) gene of IBV. The RT-PCR products of four IBV isolates were sequenced. The results showed that from 25 examined flocks with respiratory disease, 12 flocks (48.00%) were positive for IBV. In phylogenetic analysis, our isolates were closely related to the QX-like viruses such as PCRLab/06/2012 (Iran), QX, HC9, HC10, CK/CH/GX/NN11-1, CK/CH/JS/YC11-1, CK/CH/JS/2010/13, CK/CH/JS/2011/2 (China), QX/SGK-21, QX/SGK-11 (Iraq) with nucleotide homology up to 99.00%. This study indicates the role of IBVs in the respiratory disorders of broiler flocks located in southwest Iran, and also the existence of a variant of IBV, which is distinguishable from the other Iranian variants.",2018 Sep 15 Summer,"['Boroomand, Zahra', 'Jafari, Ramezan Ali', 'Mayahi, Mansour']",Vet Res Forum,,,True
9f78883fead290d4f822852fbd953b2b2cfbb566,PMC,Epidemic and pandemic-prone diseases,,PMC6201038,,CC BY-NC-SA,,2018 Oct,,Saudi Med J,,,False
2c074099e6063fd2570cb173900da087fba991f5,PMC,Respiratory failure in the hematopoietic stem cell transplant recipient,http://dx.doi.org/10.5492/wjccm.v7.i5.62,PMC6201323,30370228,CC BY-NC,"The number of patients receiving hematopoietic stem cell transplantation (HSCT) is rapidly rising worldwide. Despite substantial improvements in peri-transplant care, pulmonary complications resulting in respiratory failure remain a major contributor to morbidity and mortality in the post-transplant period, and represent a major barrier to the overall success of HSCT. Infectious complications include pneumonia due to bacteria, viruses, and fungi, and most commonly occur during neutropenia in the early post-transplant period. Non-infectious complications include idiopathic pneumonia syndrome, peri-engraftment respiratory distress syndrome, diffuse alveolar hemorrhage, pulmonary veno-occlusive disease, delayed pulmonary toxicity syndrome, cryptogenic organizing pneumonia, bronchiolitis obliterans syndrome, and post-transplant lymphoproliferative disorder. These complications have distinct clinical features and risk factors, occur at differing times following transplant, and contribute to morbidity and mortality.",2018 Oct 16,"['Wieruszewski, Patrick M', 'Herasevich, Svetlana', 'Gajic, Ognjen', 'Yadav, Hemang']",World J Crit Care Med,,,True
e222c3bbd05eb665b185124594a7d85712735418,PMC,Clinical and sero-molecular characterization of Escherichia coli with an emphasis on hybrid strain in healthy and diarrheic neonatal calves in Egypt,http://dx.doi.org/10.4314/ovj.v8i4.1,PMC6203894,30425958,CC BY-NC-SA,"The present study was carried out to characterize pathogenic E. coli in apparently healthy and diarrheic neonatal calves with special reference to the hybrid E. coli strains and evaluate their clinical and hematobiochemical consequences. One hundred and seventy calves (age 1-30 days) were divided into two groups: apparently healthy (n = 70) and diarrheic (n=100). Animals were subjected to thorough clinical, hematobiochemical and bacteriological examinations. Clinically, diarrheic calves showed various degree of diarrhea with the presence of cardinal signs of dehydration in moderate and severe cases. There was a significant increase (p<0.05) in the hemogram parameters with uremia and hyperkalemia in calves with severe diarrhea. The O-H serotyping of cultural and biochemically positive isolates identified 31 isolates belonging to 12 serotypes including O44:H18, O55:H7, O146:H21, O113:H4, O121:H7, O26:H11, O91:H21, O111:H2, O8, O127: H6, O86 and O128:H2. Molecular characterization of E. coli isolates on three toxin genes: heat-stable enterotoxin (sta), shiga toxin type 1 and 2 (stx1 and stx2) revealed two well-known pathotypes (EPEC O44:H18, O55:H7, O146:H21, O113:H4, O121:H7 and EHEC O26:H11 O91:H21 O111:H2) with high frequency of enterohemorrhagic E. coli (EHEC). Molecular analysis also showed a number of E. coli isolates that carry sta and stx1 or sta and stx2 gene and belonged to O8, and O127:H6, O86 and O128:H2. These isolates were identified as hybrid E. coli strains (ETEC-STEC) and found in both apparently healthy and diarrheic calves. In conclusion, the present study identified high frequency of pathogenic E. coli in both apparently healthy and diarrheic calves. Serological and molecular analysis of E. coli isolates showed that high frequency of EHEC and presence of a new phenotype, STEC–ETEC hybrid, revealing their importance in the etiopathogenesis of diarrhea in calves and reinforcing the role of these animals as a reservoir of potentially pathogenic E. coli for humans.",2018 Oct 12,"['Aref, Nasr-Eldin M.', 'Abdel-Raheem, Abdel-Raheem A.', 'Kamaly, Hanaa F.', 'Hussien, Soher Z.']",Open Vet J,,,True
103228b102f34e60c7057cc68069d00194959837,PMC,mTOR inhibitors lower an intrinsic barrier to virus infection mediated by IFITM3,http://dx.doi.org/10.1073/pnas.1811892115,PMC6205447,30301809,CC BY-NC-ND,"Rapamycin and its derivatives are specific inhibitors of mammalian target of rapamycin (mTOR) kinase and, as a result, are well-established immunosuppressants and antitumorigenic agents. Additionally, this class of drug promotes gene delivery by facilitating lentiviral vector entry into cells, revealing its potential to improve gene therapy efforts. However, the precise mechanism was unknown. Here, we report that mTOR inhibitor treatment results in down-regulation of the IFN-induced transmembrane (IFITM) proteins. IFITM proteins, especially IFITM3, are potent inhibitors of virus–cell fusion and are broadly active against a range of pathogenic viruses. We found that the effect of rapamycin treatment on lentiviral transduction is diminished upon IFITM silencing or knockout in primary and transformed cells, and the extent of transduction enhancement depends on basal expression of IFITM proteins, with a major contribution from IFITM3. The effect of rapamycin treatment on IFITM3 manifests at the level of protein, but not mRNA, and is selective, as many other endosome-associated transmembrane proteins are unaffected. Rapamycin-mediated degradation of IFITM3 requires endosomal trafficking, ubiquitination, endosomal sorting complex required for transport (ESCRT) machinery, and lysosomal acidification. Since IFITM proteins exhibit broad antiviral activity, we show that mTOR inhibition also promotes infection by another IFITM-sensitive virus, Influenza A virus, but not infection by Sendai virus, which is IFITM-resistant. Our results identify the molecular basis by which mTOR inhibitors enhance virus entry into cells and reveal a previously unrecognized immunosuppressive feature of these clinically important drugs. In addition, this study uncovers a functional convergence between the mTOR pathway and IFITM proteins at endolysosomal membranes.",2018 Oct 23,"['Shi, Guoli', 'Ozog, Stosh', 'Torbett, Bruce E.', 'Compton, Alex A.']",Proc Natl Acad Sci U S A,,,True
37feea85864da899f6c9b22a7d89c8598fa38a29,PMC,mTOR inhibitors lower an intrinsic barrier to virus infection mediated by IFITM3,http://dx.doi.org/10.1073/pnas.1811892115,PMC6205447,30301809,CC BY-NC-ND,"Rapamycin and its derivatives are specific inhibitors of mammalian target of rapamycin (mTOR) kinase and, as a result, are well-established immunosuppressants and antitumorigenic agents. Additionally, this class of drug promotes gene delivery by facilitating lentiviral vector entry into cells, revealing its potential to improve gene therapy efforts. However, the precise mechanism was unknown. Here, we report that mTOR inhibitor treatment results in down-regulation of the IFN-induced transmembrane (IFITM) proteins. IFITM proteins, especially IFITM3, are potent inhibitors of virus–cell fusion and are broadly active against a range of pathogenic viruses. We found that the effect of rapamycin treatment on lentiviral transduction is diminished upon IFITM silencing or knockout in primary and transformed cells, and the extent of transduction enhancement depends on basal expression of IFITM proteins, with a major contribution from IFITM3. The effect of rapamycin treatment on IFITM3 manifests at the level of protein, but not mRNA, and is selective, as many other endosome-associated transmembrane proteins are unaffected. Rapamycin-mediated degradation of IFITM3 requires endosomal trafficking, ubiquitination, endosomal sorting complex required for transport (ESCRT) machinery, and lysosomal acidification. Since IFITM proteins exhibit broad antiviral activity, we show that mTOR inhibition also promotes infection by another IFITM-sensitive virus, Influenza A virus, but not infection by Sendai virus, which is IFITM-resistant. Our results identify the molecular basis by which mTOR inhibitors enhance virus entry into cells and reveal a previously unrecognized immunosuppressive feature of these clinically important drugs. In addition, this study uncovers a functional convergence between the mTOR pathway and IFITM proteins at endolysosomal membranes.",2018 Oct 23,"['Shi, Guoli', 'Ozog, Stosh', 'Torbett, Bruce E.', 'Compton, Alex A.']",Proc Natl Acad Sci U S A,,,True
069695d115517cbd0e713fb44245be7a6226bc7f,PMC,Studies of nonhuman primates: key sources of data on zoonoses and microbiota,http://dx.doi.org/10.1016/j.nmni.2018.08.014,PMC6205567,30402252,CC BY-NC-ND,"The genetic and morphologic similarities between primates and humans means that much information obtained from primates may be applied to humans, and vice versa. However, habitat loss, hunting and the continued presence of humans have a negative effect on the biology and behaviour of almost all nonhuman primates. Noninvasive methods such as stool collection are among the safest alternative ways to study the multiple aspects of the biology of primates. Many epidemiologic issues (e.g. pathogen detection, microbiota studies) may be easily studied using stool samples from primates. Primates are undoubtedly among the first candidates suspected of becoming the source of one of the next emerging epidemic of zoonotic origin, as has already been observed with HIV, malaria and monkeypox. The Institut Hospitalo-Universitaire Méditerranée Infection in Marseille actively participates in the study, mostly epidemiologic, of nonhuman primates, using mostly stool samples.",2018 Aug 30,"['Davoust, B.', 'Levasseur, A.', 'Mediannikov, O.']",New Microbes New Infect,,,False
c5f2db5c9d68ec18bad931bbbc31bc535e5cb3a6,PMC,Highly infectious diseases in the Mediterranean Sea area: Inventory of isolation capabilities and recommendations for appropriate isolation,http://dx.doi.org/10.1016/j.nmni.2018.08.013,PMC6205579,30402245,CC BY-NC-ND,"Epidemics such as viral haemorrhagic fevers, severe acute respiratory syndrome, Middle East respiratory syndrome coronavirus or yet unknown ones have few chances of disappearing. Globalization, worldwide travel, climate change, social conflicts and wars, among others, are likely to favor the emergence of epidemics. Preparedness of hospitals to prevent the spread of these outbreaks is among the prioritized political programmes of many countries. The EuroNHID network has in the past drawn a map of features and equipment of hospitals across Europe to take care of highly contagious patients. We update the data regarding isolation capabilities and recommendations, with an emphasis on Mediterranean countries.",2018 Aug 30,"['Fusco, F.M.', 'Brouqui, P.', 'Ippolito, G.', None]",New Microbes New Infect,,,False
7d1b56a1da849ab1a3e0ee57807511ebac91de24,PMC,Comparison of conservative therapy and steroid therapy for Bell’s palsy in children,http://dx.doi.org/10.3345/kjp.2018.06380,PMC6212712,30304913,CC BY-NC,"PURPOSE: Bell’s palsy is characterized by sudden onset of unilateral facial weakness. The use of corticosteroids for childhood Bell’s palsy is controversial. This study aimed to identify clinical characteristics, etiology, and laboratory findings in childhood Bell’s palsy, and to evaluate the efficacy of corticosteroid treatment. METHODS: We conducted a retrospective analysis of children under 19 years of age treated for Bell’s palsy between January 2009 and June 2017, and followed up for over 1 month. Clinical characteristics, neuroimaging data, laboratory findings, treatments, and outcomes were reviewed. Patients with Bell’s palsy were divided into groups with (group 1) and without (group 2) corticosteroid treatment. Differences in onset age, sex, laterality, infection and vaccination history, degree of facial nerve palsy, and prognosis after treatment between the groups were analyzed. RESULTS: One hundred patients were included. Mean age at presentation was 7.4±5.62 years. A total of 73 patients (73%) received corticosteroids with or without intravenous antiviral agents, and 27 (27%) received only supportive treatment. There was no significant difference in the severity, laboratory findings, or neuroimaging findings between the groups. Significant improvement was observed in 68 (93.2%) and 26 patients (96.3%) in groups 1 and 2, respectively; this rate was not significantly different between the groups (P=0.48). CONCLUSION: Childhood Bell’s palsy showed good prognosis with or without corticosteroid treatment; there was no difference in prognosis between treated and untreated groups. Steroid therapy in childhood Bell’s palsy may not significantly improve outcomes.",2018 Oct 12,"['Yoo, Hye Won', 'Yoon, Lira', 'Kim, Hye Young', 'Kwak, Min Jung', 'Park, Kyung Hee', 'Bae, Mi Hye', 'Lee, Yunjin', 'Nam, Sang Ook', 'Kim, Young Mi']",Korean J Pediatr,,,True
01de46a248049d2fbdc049b686ee5b172301d0fa,PMC,Pericollapse Stage of Osteonecrosis of the Femoral Head: A Last Chance for Joint Preservation,http://dx.doi.org/10.4103/0366-6999.244111,PMC6213842,30381593,CC BY-NC-SA,"OBJECTIVE: To propose a new definition of the pericollapse stage of osteonecrosis of the femoral head (ONFH) and review its significance in disease diagnosis and treatment selection. DATA SOURCES: A search for eligible studies was conducted in three electronic databases including PubMed, Cochrane Library, and Embase up to August 10, 2018, using the following keywords: “osteonecrosis”, “prognosis”, and “treatment”. STUDY SELECTION: Investigations appraising the clinical signs, symptoms, and imaging manifestations in different stages of ONFH were included. Articles evaluating the prognosis of various joint-preserving procedures were also reviewed. RESULTS: The pericollapse stage refers to a continuous period in the development of ONFH from the occurrence of subchondral fracture to early collapse (<2 mm), possessing specific imaging features that mainly consist of bone marrow edema and joint effusion on magnetic resonance imaging (MRI), crescent signs on X-ray films, and clinical manifestations such as the sudden worsening of hip pain. Accumulating evidence has indicated that these findings may be secondary to the changes after subchondral fractures. Of note, computed tomography provides more information for identifying possible subchondral fractures than does MRI and serves as the most sensitive tool for grading the pericollapse lesion stage. The pericollapse stage may indicate a high possibility of progressive disease but also demonstrates satisfactory long- and medium-term outcomes for joint-preserving techniques. In fact, if the articular surface subsides more than 2 mm, total hip arthroplasty is preferable. CONCLUSIONS: The pericollapse stage with distinct clinical and imaging characteristics provides a last good opportunity for the use of joint-preserving techniques. It is necessary to separate the pericollapse stage as an independent state in evaluating the natural progression of ONFH and selecting an appropriate treatment regimen.",2018 Nov 5,"['Zhang, Qing-Yu', 'Li, Zi-Rong', 'Gao, Fu-Qiang', 'Sun, Wei']",Chin Med J (Engl),,,True
26fec23192bed03196a134abb20b8b197a2acc42,PMC,Single‐cell transcriptomics reveals distinct inflammation‐induced microglia signatures,http://dx.doi.org/10.15252/embr.201846171,PMC6216255,30206190,CC BY-NC-ND,"Microglia are specialized parenchymal‐resident phagocytes of the central nervous system (CNS) that actively support, defend and modulate the neural environment. Dysfunctional microglial responses are thought to worsen CNS diseases; nevertheless, their impact during neuroinflammatory processes remains largely obscure. Here, using a combination of single‐cell RNA sequencing and multicolour flow cytometry, we comprehensively profile microglia in the brain of lipopolysaccharide (LPS)‐injected mice. By excluding the contribution of other immune CNS‐resident and peripheral cells, we show that microglia isolated from LPS‐injected mice display a global downregulation of their homeostatic signature together with an upregulation of inflammatory genes. Notably, we identify distinct microglial activated profiles under inflammatory conditions, which greatly differ from neurodegenerative disease‐associated profiles. These results provide insights into microglial heterogeneity and establish a resource for the identification of specific phenotypes in CNS disorders, such as neuroinflammatory and neurodegenerative diseases.",2018 Nov 11,"['Sousa, Carole', 'Golebiewska, Anna', 'Poovathingal, Suresh K', 'Kaoma, Tony', 'Pires‐Afonso, Yolanda', 'Martina, Silvia', 'Coowar, Djalil', 'Azuaje, Francisco', 'Skupin, Alexander', 'Balling, Rudi', 'Biber, Knut', 'Niclou, Simone P', 'Michelucci, Alessandro']",EMBO Rep,,,True
3e80b66b079cce399e318efd422d791965557d18,PMC,Single‐cell transcriptomics reveals distinct inflammation‐induced microglia signatures,http://dx.doi.org/10.15252/embr.201846171,PMC6216255,30206190,CC BY-NC-ND,"Microglia are specialized parenchymal‐resident phagocytes of the central nervous system (CNS) that actively support, defend and modulate the neural environment. Dysfunctional microglial responses are thought to worsen CNS diseases; nevertheless, their impact during neuroinflammatory processes remains largely obscure. Here, using a combination of single‐cell RNA sequencing and multicolour flow cytometry, we comprehensively profile microglia in the brain of lipopolysaccharide (LPS)‐injected mice. By excluding the contribution of other immune CNS‐resident and peripheral cells, we show that microglia isolated from LPS‐injected mice display a global downregulation of their homeostatic signature together with an upregulation of inflammatory genes. Notably, we identify distinct microglial activated profiles under inflammatory conditions, which greatly differ from neurodegenerative disease‐associated profiles. These results provide insights into microglial heterogeneity and establish a resource for the identification of specific phenotypes in CNS disorders, such as neuroinflammatory and neurodegenerative diseases.",2018 Nov 11,"['Sousa, Carole', 'Golebiewska, Anna', 'Poovathingal, Suresh K', 'Kaoma, Tony', 'Pires‐Afonso, Yolanda', 'Martina, Silvia', 'Coowar, Djalil', 'Azuaje, Francisco', 'Skupin, Alexander', 'Balling, Rudi', 'Biber, Knut', 'Niclou, Simone P', 'Michelucci, Alessandro']",EMBO Rep,,,False
a263a1551a68f5e5e0f272166364fe171cc49b06,PMC,Single‐cell transcriptomics reveals distinct inflammation‐induced microglia signatures,http://dx.doi.org/10.15252/embr.201846171,PMC6216255,30206190,CC BY-NC-ND,"Microglia are specialized parenchymal‐resident phagocytes of the central nervous system (CNS) that actively support, defend and modulate the neural environment. Dysfunctional microglial responses are thought to worsen CNS diseases; nevertheless, their impact during neuroinflammatory processes remains largely obscure. Here, using a combination of single‐cell RNA sequencing and multicolour flow cytometry, we comprehensively profile microglia in the brain of lipopolysaccharide (LPS)‐injected mice. By excluding the contribution of other immune CNS‐resident and peripheral cells, we show that microglia isolated from LPS‐injected mice display a global downregulation of their homeostatic signature together with an upregulation of inflammatory genes. Notably, we identify distinct microglial activated profiles under inflammatory conditions, which greatly differ from neurodegenerative disease‐associated profiles. These results provide insights into microglial heterogeneity and establish a resource for the identification of specific phenotypes in CNS disorders, such as neuroinflammatory and neurodegenerative diseases.",2018 Nov 11,"['Sousa, Carole', 'Golebiewska, Anna', 'Poovathingal, Suresh K', 'Kaoma, Tony', 'Pires‐Afonso, Yolanda', 'Martina, Silvia', 'Coowar, Djalil', 'Azuaje, Francisco', 'Skupin, Alexander', 'Balling, Rudi', 'Biber, Knut', 'Niclou, Simone P', 'Michelucci, Alessandro']",EMBO Rep,,,False
68fe7e9a2c5857167b70d9499372dc3dd5cdde06,PMC,Single‐cell transcriptomics reveals distinct inflammation‐induced microglia signatures,http://dx.doi.org/10.15252/embr.201846171,PMC6216255,30206190,CC BY-NC-ND,"Microglia are specialized parenchymal‐resident phagocytes of the central nervous system (CNS) that actively support, defend and modulate the neural environment. Dysfunctional microglial responses are thought to worsen CNS diseases; nevertheless, their impact during neuroinflammatory processes remains largely obscure. Here, using a combination of single‐cell RNA sequencing and multicolour flow cytometry, we comprehensively profile microglia in the brain of lipopolysaccharide (LPS)‐injected mice. By excluding the contribution of other immune CNS‐resident and peripheral cells, we show that microglia isolated from LPS‐injected mice display a global downregulation of their homeostatic signature together with an upregulation of inflammatory genes. Notably, we identify distinct microglial activated profiles under inflammatory conditions, which greatly differ from neurodegenerative disease‐associated profiles. These results provide insights into microglial heterogeneity and establish a resource for the identification of specific phenotypes in CNS disorders, such as neuroinflammatory and neurodegenerative diseases.",2018 Nov 11,"['Sousa, Carole', 'Golebiewska, Anna', 'Poovathingal, Suresh K', 'Kaoma, Tony', 'Pires‐Afonso, Yolanda', 'Martina, Silvia', 'Coowar, Djalil', 'Azuaje, Francisco', 'Skupin, Alexander', 'Balling, Rudi', 'Biber, Knut', 'Niclou, Simone P', 'Michelucci, Alessandro']",EMBO Rep,,,False
12666bbfb4382c1c684087fa6343d5c03cea8584,PMC,Single‐cell transcriptomics reveals distinct inflammation‐induced microglia signatures,http://dx.doi.org/10.15252/embr.201846171,PMC6216255,30206190,CC BY-NC-ND,"Microglia are specialized parenchymal‐resident phagocytes of the central nervous system (CNS) that actively support, defend and modulate the neural environment. Dysfunctional microglial responses are thought to worsen CNS diseases; nevertheless, their impact during neuroinflammatory processes remains largely obscure. Here, using a combination of single‐cell RNA sequencing and multicolour flow cytometry, we comprehensively profile microglia in the brain of lipopolysaccharide (LPS)‐injected mice. By excluding the contribution of other immune CNS‐resident and peripheral cells, we show that microglia isolated from LPS‐injected mice display a global downregulation of their homeostatic signature together with an upregulation of inflammatory genes. Notably, we identify distinct microglial activated profiles under inflammatory conditions, which greatly differ from neurodegenerative disease‐associated profiles. These results provide insights into microglial heterogeneity and establish a resource for the identification of specific phenotypes in CNS disorders, such as neuroinflammatory and neurodegenerative diseases.",2018 Nov 11,"['Sousa, Carole', 'Golebiewska, Anna', 'Poovathingal, Suresh K', 'Kaoma, Tony', 'Pires‐Afonso, Yolanda', 'Martina, Silvia', 'Coowar, Djalil', 'Azuaje, Francisco', 'Skupin, Alexander', 'Balling, Rudi', 'Biber, Knut', 'Niclou, Simone P', 'Michelucci, Alessandro']",EMBO Rep,,,True
b9e6621f5b788746ecf6f648b00844b10634d43f,PMC,On‐Chip Screening of a Glycomimetic Library with C‐Type Lectins Reveals Structural Features Responsible for Preferential Binding of Dectin‐2 over DC‐SIGN/R and Langerin,http://dx.doi.org/10.1002/chem.201802577,PMC6220942,29975429,CC BY-NC-ND,"A library of mannose‐ and fucose‐based glycomimetics was synthesized and screened in a microarray format against a set of C‐type lectin receptors (CLRs) that included DC‐SIGN, DC‐SIGNR, langerin, and dectin‐2. Glycomimetic ligands able to interact with dectin‐2 were identified for the first time. Comparative analysis of binding profiles allowed their selectivity against other CLRs to be probed.",2018 Sep 25,"['Medve, Laura', 'Achilli, Silvia', 'Serna, Sonia', 'Zuccotto, Fabio', 'Varga, Norbert', 'Thépaut, Michel', 'Civera, Monica', 'Vivès, Corinne', 'Fieschi, Franck', 'Reichardt, Niels', 'Bernardi, Anna']",Chemistry,,,True
ec4342e09dc05955d87c6ae10d17544561133bfb,PMC,On‐Chip Screening of a Glycomimetic Library with C‐Type Lectins Reveals Structural Features Responsible for Preferential Binding of Dectin‐2 over DC‐SIGN/R and Langerin,http://dx.doi.org/10.1002/chem.201802577,PMC6220942,29975429,CC BY-NC-ND,"A library of mannose‐ and fucose‐based glycomimetics was synthesized and screened in a microarray format against a set of C‐type lectin receptors (CLRs) that included DC‐SIGN, DC‐SIGNR, langerin, and dectin‐2. Glycomimetic ligands able to interact with dectin‐2 were identified for the first time. Comparative analysis of binding profiles allowed their selectivity against other CLRs to be probed.",2018 Sep 25,"['Medve, Laura', 'Achilli, Silvia', 'Serna, Sonia', 'Zuccotto, Fabio', 'Varga, Norbert', 'Thépaut, Michel', 'Civera, Monica', 'Vivès, Corinne', 'Fieschi, Franck', 'Reichardt, Niels', 'Bernardi, Anna']",Chemistry,,,False
26800b3eaee2dc23b411ad506c255ab5133a8608,PMC,Regulating gene expression in animals through RNA endonucleolytic cleavage,http://dx.doi.org/10.1016/j.heliyon.2018.e00908,PMC6223193,30426105,CC BY-NC-ND,"The expression of any gene must be precisely controlled for appropriate function. This expression can be controlled at various levels. This includes epigenetic regulation through DNA methylation or histone modifications. At the posttranscriptional level, regulation can be via alternative splicing or controlling messenger RNA (mRNA) stability. RNA cleavage is one way to control mRNA stability. For example, microRNA (miRNA)-induced mRNA cleavage has long been recognised in plants. RNA cleavage also appears to be widespread in other kingdoms of life, and it is now clear that mRNA cleavage plays critical functions in animals. Although miRNA-induced mRNA cleavage can occur in animals, it is not a widespread mechanism. Instead, mRNA cleavage can be induced by a range of other mechanisms, including by endogenous short inhibitory RNAs (endo-siRNAs), as well as the Ribonuclease III (RNase III) enzymes Drosha and Dicer. In addition, RNA cleavage induced by endo-siRNAs and PIWI-interacting RNAs (piRNAs) is important for genome defence against transposons. Moreover, several RNase has been identified as important antiviral mediators. In this review, we will discuss these various RNA endonucleolytic cleavage mechanisms utilised by animals to regulate the expression of genes and as a defence against retrotransposons and viral infection.",2018 Nov 2,"['Gu, Karen', 'Mok, Lawrence', 'Chong, Mark M.W.']",Heliyon,,,False
c84aa58b12823cdd6f119b4da3b0c4ba488856b5,PMC,Digital Epidemiology: Use of Digital Data Collected for Non-epidemiological Purposes in Epidemiological Studies,http://dx.doi.org/10.4258/hir.2018.24.4.253,PMC6230537,30443413,CC BY-NC,"OBJECTIVES: We reviewed digital epidemiological studies to characterize how researchers are using digital data by topic domain, study purpose, data source, and analytic method. METHODS: We reviewed research articles published within the last decade that used digital data to answer epidemiological research questions. Data were abstracted from these articles using a data collection tool that we developed. Finally, we summarized the characteristics of the digital epidemiological studies. RESULTS: We identified six main topic domains: infectious diseases (58.7%), non-communicable diseases (29.4%), mental health and substance use (8.3%), general population behavior (4.6%), environmental, dietary, and lifestyle (4.6%), and vital status (0.9%). We identified four categories for the study purpose: description (22.9%), exploration (34.9%), explanation (27.5%), and prediction and control (14.7%). We identified eight categories for the data sources: web search query (52.3%), social media posts (31.2%), web portal posts (11.9%), webpage access logs (7.3%), images (7.3%), mobile phone network data (1.8%), global positioning system data (1.8%), and others (2.8%). Of these, 50.5% used correlation analyses, 41.3% regression analyses, 25.6% machine learning, and 19.3% descriptive analyses. CONCLUSIONS: Digital data collected for non-epidemiological purposes are being used to study health phenomena in a variety of topic domains. Digital epidemiology requires access to large datasets and advanced analytics. Ensuring open access is clearly at odds with the desire to have as little personal data as possible in these large datasets to protect privacy. Establishment of data cooperatives with restricted access may be a solution to this dilemma.",2018 Oct 31,"['Park, Hyeoun-Ae', 'Jung, Hyesil', 'On, Jeongah', 'Park, Seul Ki', 'Kang, Hannah']",Healthc Inform Res,,,True
15068678ec0fe7fd4ee563d914de8dad612bc98a,PMC,Developing metrics for emergency care research in low- and middle-income countries,http://dx.doi.org/10.1016/j.afjem.2016.06.003,PMC6234170,30456077,CC BY-NC-ND,"INTRODUCTION: There is little research on emergency care delivery in low- and middle-income countries (LMICs). To facilitate future research, we aimed to assess the set of key metrics currently used by researchers in these settings and to propose a set of standard metrics to facilitate future research. METHODS: Systematic literature review of 43,109 published reports on general emergency care from 139 LMICs. Studies describing care for subsets of emergency conditions, subsets of populations, and data aggregated across multiple facilities were excluded. All facility- and patient-level statistics reported in these studies were recorded and the most commonly used metrics were identified. RESULTS: We identified 195 studies on emergency care delivery in LMICs. There was little uniformity in either patient- or facility-level metrics reported. Patient demographics were inconsistently reported: only 33% noted average age and 63% the gender breakdown. The upper age boundary used for paediatric data varied widely, from 5 to 20 years of age. Emergency centre capacity was reported using a variety of metrics including annual patient volume (n = 175, 90%); bed count (n = 60, 31%), number of rooms (n = 48, 25%); frequently none of these metrics were reported (n = 16, 8%). Many characteristics essential to describe capabilities and performance of emergency care were not reported, including use and type of triage; level of provider training; admission rate; time to evaluation; and length of EC stay. CONCLUSION: We found considerable heterogeneity in reporting practices for studies of emergency care in LMICs. Standardised metrics could facilitate future analysis and interpretation of such studies, and expand the ability to generalise and compare findings across emergency care settings.",2016 Sep 12,"['Abujaber, Samer', 'Chang, Cindy Y.', 'Reynolds, Teri A.', 'Mowafi, Hani', 'Obermeyer, Ziad']",Afr J Emerg Med,,,False
4090c4a0e8cead64dd9e44a1610fb4f557fefdcf,PMC,Evaluation of Zika Virus-specific T-cell Responses in Immunoprivileged Organs of Infected Ifnar1(-/-) Mice,http://dx.doi.org/10.3791/58110,PMC6235543,30394402,CC BY-NC-ND,"The Zika virus (ZIKV) can induce inflammation in immunoprivileged organs (e.g., the brain and testis), leading to the Guillain-Barré syndrome and damaging the testes. During an infection with the ZIKV, immune cells have been shown to infiltrate into the tissues. However, the cellular mechanisms that define the protection and/or immunopathogenesis of these immune cells during a ZIKV infection are still largely unknown. Herein, we describe methods to evaluate the virus-specific T-cell functionality in these immunoprivileged organs of ZIKV-infected mice. These methods include a) a ZIKV infection and vaccine inoculation in Ifnar1(-/-) mice; b) histopathology, immunofluorescence, and immunohistochemistry assays to detect the virus infection and inflammation in the brain, testes, and spleen; c) the preparation of a tetramer of ZIKV-derived T-cell epitopes; d) the detection of ZIKV-specific T cells in the monocytes isolated from the brain, testes, and spleen. Using these approaches, it is possible to detect the antigen-specific T cells that have infiltrated into the immunoprivileged organs and to evaluate the functions of these T cells during the infection: potential immune protection via virus clearance and/or immunopathogenesis to exacerbate the inflammation. These findings may also help to clarify the contribution of T cells induced by the immunization against ZIKV.",2018 Oct 17,"['Zhang, Yongli', 'Zhang, Hangjie', 'Ma, Wenqiang', 'Liu, Kefang', 'Zhao, Min', 'Zhao, Yingze', 'Lu, Xuancheng', 'Zhang, Fuping', 'Li, Xiangdong', 'Gao, George F.', 'Liu, William J.']",J Vis Exp,,,True
f0ec075fb3dafe5c5815a641fc8ae543b30f36fd,PMC,"Nucleolar Localization of HIV-1 Rev Is Required, Yet Insufficient for Production of Infectious Viral Particles",http://dx.doi.org/10.1089/aid.2017.0306,PMC6238656,29804468,CC BY-NC,"Combination antiretroviral therapy fails in complete suppression of HIV-1 due to drug resistance and persistent latency. Novel therapeutic intervention requires knowledge of intracellular pathways responsible for viral replication, specifically those untargeted by antiretroviral drugs. An understudied phenomenon is the nucleolar localization of Rev phosphoprotein, which completes nucleocytoplasmic transport of unspliced/partially spliced HIV mRNA through multimerization with intronic cis-acting targets—the Rev-response element (RRE). Rev contains a nucleolar localization signal (NoLS) comprising the COOH terminus of the arginine-rich motif for accumulation within nucleoli—speculated as the interaction ground for Rev with cellular proteins mediating mRNA-independent nuclear export and splicing. Functionality of Rev nucleolar access during HIV-1 production and infection was investigated in the context of deletion and single-point mutations within Rev-NoLS. Mutations induced upon Rev-NoLS are hypothesized to inactivate the HIV-1 infectious cycle. HIV-1(HXB2) replication ceased with Rev mutations lacking nucleolar access due to loss or replacement of multiple arginine residues. Rev mutations missing single arginine residues remained strictly nucleolar in pattern and participated in proviral production, however, with reduced efficiency. Viral RNA packaging also decreased in efficiency after expression of nucleolar-localizing mutations. These results were observed during propagation of variant HIV-1(NL4-3) containing nucleolar-localizing mutations within the viral backbone (M4, M5, and M6). Lentiviral particles produced with Rev single-point mutations were transducible at extremely low frequency. Similarly, HIV-1(NL4-3) Rev-NoLS variants lost infectivity, unlike virulent WT (wild type) HIV-1(NL4-3). HIV-1(NL4-3) variants were capable of CD4(+) host entry and reverse transcription as WT HIV-1(NL4-3), but lacked ability to complete a full infectious cycle. We currently reveal that viral integration is deregulated in the presence of Rev-NoLS mutations.",2018 Nov 1,"['Arizala, Jerlisa Ann C.', 'Takahashi, Mayumi', 'Burnett, John C.', 'Ouellet, Dominique L.', 'Li, Haitang', 'Rossi, John J.']",AIDS Res Hum Retroviruses,,,True
b54ed16382ae289770e7df71e3f304f5ad2fbabd,PMC,"Nucleolar Localization of HIV-1 Rev Is Required, Yet Insufficient for Production of Infectious Viral Particles",http://dx.doi.org/10.1089/aid.2017.0306,PMC6238656,29804468,CC BY-NC,"Combination antiretroviral therapy fails in complete suppression of HIV-1 due to drug resistance and persistent latency. Novel therapeutic intervention requires knowledge of intracellular pathways responsible for viral replication, specifically those untargeted by antiretroviral drugs. An understudied phenomenon is the nucleolar localization of Rev phosphoprotein, which completes nucleocytoplasmic transport of unspliced/partially spliced HIV mRNA through multimerization with intronic cis-acting targets—the Rev-response element (RRE). Rev contains a nucleolar localization signal (NoLS) comprising the COOH terminus of the arginine-rich motif for accumulation within nucleoli—speculated as the interaction ground for Rev with cellular proteins mediating mRNA-independent nuclear export and splicing. Functionality of Rev nucleolar access during HIV-1 production and infection was investigated in the context of deletion and single-point mutations within Rev-NoLS. Mutations induced upon Rev-NoLS are hypothesized to inactivate the HIV-1 infectious cycle. HIV-1(HXB2) replication ceased with Rev mutations lacking nucleolar access due to loss or replacement of multiple arginine residues. Rev mutations missing single arginine residues remained strictly nucleolar in pattern and participated in proviral production, however, with reduced efficiency. Viral RNA packaging also decreased in efficiency after expression of nucleolar-localizing mutations. These results were observed during propagation of variant HIV-1(NL4-3) containing nucleolar-localizing mutations within the viral backbone (M4, M5, and M6). Lentiviral particles produced with Rev single-point mutations were transducible at extremely low frequency. Similarly, HIV-1(NL4-3) Rev-NoLS variants lost infectivity, unlike virulent WT (wild type) HIV-1(NL4-3). HIV-1(NL4-3) variants were capable of CD4(+) host entry and reverse transcription as WT HIV-1(NL4-3), but lacked ability to complete a full infectious cycle. We currently reveal that viral integration is deregulated in the presence of Rev-NoLS mutations.",2018 Nov 1,"['Arizala, Jerlisa Ann C.', 'Takahashi, Mayumi', 'Burnett, John C.', 'Ouellet, Dominique L.', 'Li, Haitang', 'Rossi, John J.']",AIDS Res Hum Retroviruses,,,False
5fc9523915b057c03afa54f111fe9fd1995dd1ad,PMC,Cyclophilin A as a target in the treatment of cytomegalovirus infections,http://dx.doi.org/10.1177/2040206618811413,PMC6243413,30449131,CC BY-NC,"BACKGROUND: Viruses are obligate parasites that depend on the cellular machinery of the host to regenerate and manufacture their proteins. Most antiviral drugs on the market today target viral proteins. However, the more recent strategies involve targeting the host cell proteins or pathways that mediate viral replication. This new approach would be effective for most viruses while minimizing drug resistance and toxicity. METHODS: Cytomegalovirus replication, latency, and immune response are mediated by the intermediate early protein 2, the main protein that determines the effectiveness of drugs in cytomegalovirus inhibition. This review explains how intermediate early protein 2 can modify the action of cyclosporin A, an immunosuppressive, and antiviral drug. It also links all the pathways mediated by cyclosporin A, cytomegalovirus replication, and its encoded proteins. RESULTS: Intermediate early protein 2 can influence the cellular cyclophilin A pathway, affecting cyclosporin A as a mediator of viral replication or anti-cytomegalovirus drug. CONCLUSION: Cyclosporin A has a dual function in cytomegalovirus pathogenesis. It has the immunosuppressive effect that establishes virus replication through the inhibition of T-cell function. It also has an anti-cytomegalovirus effect mediated by intermediate early protein 2. Both of these functions involve cyclophilin A pathway.",2018 Nov 18,"['A Abdullah, Ashwaq', 'Abdullah, Rasedee', 'A Nazariah, Zeenathul', 'N Balakrishnan, Krishnan', 'Firdaus J Abdullah, Faez', 'A Bala, Jamilu', 'Mohd-Lila, Mohd-Azmi']",Antivir Chem Chemother,,,True
83303635687128ac583152565ba1d7e29540f2af,PMC,Health care-associated infections – an overview,http://dx.doi.org/10.2147/IDR.S177247,PMC6245375,30532565,CC BY-NC,"Health care-associated infections (HCAIs) are infections that occur while receiving health care, developed in a hospital or other health care facility that first appear 48 hours or more after hospital admission, or within 30 days after having received health care. Multiple studies indicate that the common types of adverse events affecting hospitalized patients are adverse drug events, HCAIs, and surgical complications. The US Center for Disease Control and Prevention identifies that nearly 1.7 million hospitalized patients annually acquire HCAIs while being treated for other health issues and that more than 98,000 patients (one in 17) die due to these. Several studies suggest that simple infection-control procedures such as cleaning hands with an alcohol-based hand rub can help prevent HCAIs and save lives, reduce morbidity, and minimize health care costs. Routine educational interventions for health care professionals can help change their hand-washing practices to prevent the spread of infection. In support of this, the WHO has produced guidelines to promote hand-washing practices among member countries.",2018 Nov 15,"['Haque, Mainul', 'Sartelli, Massimo', 'McKimm, Judy', 'Abu Bakar, Muhamad']",Infect Drug Resist,,,True
2ead29b6cd37834fcfae2fcd41acbffc821f85ae,PMC,"Travel, Migration and Emerging Infectious Diseases",,PMC6247124,30479600,CC BY-NC,"Emerging infectious diseases (EID) threaten public health and are sustained by increasing global commerce, travel and disruption of ecological systems. Travelers could play a role in importing EIDs and could be a sentinel of major epidemics. In connection with the extension of poverty, urbanization, extensive livestock rearing and globalization, we could be exposed to a third epidemiological transition characterized by zoonotic diseases and infections with multidrug-resistant bacteria. The risk appears low for emerging infectious diseases, or very low for high-risk emerging infectious diseases, but higher for multidrug-resistant enterobacteriaceae carriage with possibly limited consequences. The role played by migrants is weaker than imagined. Immigrants don’t play the role of sentinel epidemic so far. They could play a role in importing multidrug-resistant enterobacteriaceae, but it is poorly evaluated.",2018 Nov 7,"['Vignier, Nicolas', 'Bouchaud, Olivier']",EJIFCC,,,True
996e815518a05c8d1a296afc435aa2fbe396fd14,PMC,Laboratory Medicine: Meeting the Needs of Mediterranean Nations,,PMC6247136,30479597,CC BY-NC,,2018 Nov 7,,EJIFCC,,,False
afaa73edec3f6944af5018e8426d3333d3a9986a,PMC,Autophagy-Associated Proteins Control Ebola Virus Internalization Into Host Cells,http://dx.doi.org/10.1093/infdis/jiy294,PMC6249560,29947774,CC BY-NC-ND,"Ebola virus (EBOV) enters host cells by macropinocytosis, a poorly understood process. Recent studies have suggested that cell factors involved in autophagy, an evolutionally conserved pathway leading to the lysosomal degradation of protein aggregates and organelles during cellular stress, also have roles in macropinocytosis. Here, we demonstrate that autophagy-associated proteins are required for trafficking of EBOV into the cell body. Depleting cells of beclin 1, autophagy-related protein 7, or microtubule-associated protein 1A/B light chain 3B (LC3B) abolished EBOV uptake, owing to a block in vesicle formation at the cell surface. Both LC3B-I and LC3B-II interacted with macropinocytic structures. Our work indicates that, although various forms of LC3B possess an inherent ability to associate with forming macropinosomes, LC3B-II is critical for internalization of macropinocytic vesicles and, therefore, EBOV from the cell surface.",2018 Dec 15,"['Shtanko, Olena', 'Reyes, Ann N', 'Jackson, William T', 'Davey, Robert A']",J Infect Dis,,,True
25576dd63e9bdf1bef094279010e378d096d40f2,PMC,Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate,http://dx.doi.org/10.1093/infdis/jiy377,PMC6249570,30010950,CC BY-NC-ND,"Transchromosomic bovines (Tc-bovines) adaptively produce fully human polyclonal immunoglobulin (Ig)G antibodies after exposure to immunogenic antigen(s). The National Interagency Confederation for Biological Research and collaborators rapidly produced and then evaluated anti-Ebola virus IgG immunoglobulins (collectively termed SAB-139) purified from Tc-bovine plasma after sequential hyperimmunization with an Ebola virus Makona isolate glycoprotein nanoparticle vaccine. SAB-139 was characterized by several in vitro production, research, and clinical level assays using wild-type Makona-C05 or recombinant virus/antigens from different Ebola virus variants. SAB-139 potently activates natural killer cells, monocytes, and peripheral blood mononuclear cells and has high-binding avidity demonstrated by surface plasmon resonance. SAB-139 has similar concentrations of galactose-α-1,3-galactose carbohydrates compared with human-derived intravenous Ig, and the IgG1 subclass antibody is predominant. All rhesus macaques infected with Ebola virus/H.sapiens-tc/GIN/2014/Makona-C05 and treated with sufficient SAB-139 at 1 day (n = 6) or 3 days (n = 6) postinfection survived versus 0% of controls. This study demonstrates that Tc-bovines can produce pathogen-specific human Ig to prevent and/or treat patients when an emerging infectious disease either threatens to or becomes an epidemic.",2018 Dec 15,"['Luke, Thomas', 'Bennett, Richard S', 'Gerhardt, Dawn M', 'Burdette, Tracey', 'Postnikova, Elena', 'Mazur, Steven', 'Honko, Anna N', 'Oberlander, Nicholas', 'Byrum, Russell', 'Ragland, Dan', 'St. Claire, Marisa', 'Janosko, Krisztina B', 'Smith, Gale', 'Glenn, Gregory', 'Hooper, Jay', 'Dye, John', 'Pal, Subhamoy', 'Bishop-Lilly, Kimberly A', 'Hamilton, Theron', 'Frey, Kenneth', 'Bollinger, Laura', 'Wada, Jiro', 'Wu, Hua', 'Jiao, Jin-an', 'Olinger, Gene G', 'Gunn, Bronwyn', 'Alter, Galit', 'Khurana, Surender', 'Hensley, Lisa E', 'Sullivan, Eddie', 'Jahrling, Peter B']",J Infect Dis,,,True
cb3586555dce451f217e333cec5e23ed3cd74c68,PMC,Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate,http://dx.doi.org/10.1093/infdis/jiy377,PMC6249570,30010950,CC BY-NC-ND,"Transchromosomic bovines (Tc-bovines) adaptively produce fully human polyclonal immunoglobulin (Ig)G antibodies after exposure to immunogenic antigen(s). The National Interagency Confederation for Biological Research and collaborators rapidly produced and then evaluated anti-Ebola virus IgG immunoglobulins (collectively termed SAB-139) purified from Tc-bovine plasma after sequential hyperimmunization with an Ebola virus Makona isolate glycoprotein nanoparticle vaccine. SAB-139 was characterized by several in vitro production, research, and clinical level assays using wild-type Makona-C05 or recombinant virus/antigens from different Ebola virus variants. SAB-139 potently activates natural killer cells, monocytes, and peripheral blood mononuclear cells and has high-binding avidity demonstrated by surface plasmon resonance. SAB-139 has similar concentrations of galactose-α-1,3-galactose carbohydrates compared with human-derived intravenous Ig, and the IgG1 subclass antibody is predominant. All rhesus macaques infected with Ebola virus/H.sapiens-tc/GIN/2014/Makona-C05 and treated with sufficient SAB-139 at 1 day (n = 6) or 3 days (n = 6) postinfection survived versus 0% of controls. This study demonstrates that Tc-bovines can produce pathogen-specific human Ig to prevent and/or treat patients when an emerging infectious disease either threatens to or becomes an epidemic.",2018 Dec 15,"['Luke, Thomas', 'Bennett, Richard S', 'Gerhardt, Dawn M', 'Burdette, Tracey', 'Postnikova, Elena', 'Mazur, Steven', 'Honko, Anna N', 'Oberlander, Nicholas', 'Byrum, Russell', 'Ragland, Dan', 'St. Claire, Marisa', 'Janosko, Krisztina B', 'Smith, Gale', 'Glenn, Gregory', 'Hooper, Jay', 'Dye, John', 'Pal, Subhamoy', 'Bishop-Lilly, Kimberly A', 'Hamilton, Theron', 'Frey, Kenneth', 'Bollinger, Laura', 'Wada, Jiro', 'Wu, Hua', 'Jiao, Jin-an', 'Olinger, Gene G', 'Gunn, Bronwyn', 'Alter, Galit', 'Khurana, Surender', 'Hensley, Lisa E', 'Sullivan, Eddie', 'Jahrling, Peter B']",J Infect Dis,,,False
5c08aea2dc326afc98c4359cf5f35951d13c09af,PMC,The enzymatic biosynthesis of acylated steroidal glycosides and their cytotoxic activity,http://dx.doi.org/10.1016/j.apsb.2018.04.006,PMC6251810,30505666,CC BY-NC-ND,"Herein we describe the discovery and functional characterization of a steroidal glycosyltransferase (SGT) from Ornithogalum saundersiae and a steroidal glycoside acyltransferase (SGA) from Escherichia coli and their application in the biosynthesis of acylated steroidal glycosides (ASGs). Initially, an SGT gene, designated as OsSGT1, was isolated from O. saundersiae. OsSGT1-containing cell free extract was then used as the biocatalyst to react with 49 structurally diverse drug-like compounds. The recombinant OsSGT1 was shown to be active against both 3β- and 17β-hydroxyl steroids. Unexpectedly, in an effort to identify OsSGT1, we found the bacteria lacA gene in lac operon actually encoded an SGA, specifically catalyzing the acetylations of sugar moieties of steroid 17β-glucosides. Finally, a novel enzymatic two-step synthesis of two ASGs, acetylated testosterone-17-O-β-glucosides (AT-17β-Gs) and acetylated estradiol-17-O-β-glucosides (AE-17β-Gs), from the abundantly available free steroids using OsSGT1 and EcSGA1 as the biocatalysts was developed. The two-step process is characterized by EcSGA1-catalyzed regioselective acylations of all hydroxyl groups on the sugar unit of unprotected steroidal glycosides (SGs) in the late stage, thereby significantly streamlining the synthetic route towards ASGs and thus forming four monoacylates. The improved cytotoxic activities of 3′-acetylated testosterone17-O-β-glucoside towards seven human tumor cell lines were thus observable.",2018 Oct 1,"['Liu, Ming', 'Kong, Jian-Qiang']",Acta Pharm Sin B,,,False
764bc1bd3dbbb91e1584a85a0bcb6e6ffdcee59f,PMC,The enzymatic biosynthesis of acylated steroidal glycosides and their cytotoxic activity,http://dx.doi.org/10.1016/j.apsb.2018.04.006,PMC6251810,30505666,CC BY-NC-ND,"Herein we describe the discovery and functional characterization of a steroidal glycosyltransferase (SGT) from Ornithogalum saundersiae and a steroidal glycoside acyltransferase (SGA) from Escherichia coli and their application in the biosynthesis of acylated steroidal glycosides (ASGs). Initially, an SGT gene, designated as OsSGT1, was isolated from O. saundersiae. OsSGT1-containing cell free extract was then used as the biocatalyst to react with 49 structurally diverse drug-like compounds. The recombinant OsSGT1 was shown to be active against both 3β- and 17β-hydroxyl steroids. Unexpectedly, in an effort to identify OsSGT1, we found the bacteria lacA gene in lac operon actually encoded an SGA, specifically catalyzing the acetylations of sugar moieties of steroid 17β-glucosides. Finally, a novel enzymatic two-step synthesis of two ASGs, acetylated testosterone-17-O-β-glucosides (AT-17β-Gs) and acetylated estradiol-17-O-β-glucosides (AE-17β-Gs), from the abundantly available free steroids using OsSGT1 and EcSGA1 as the biocatalysts was developed. The two-step process is characterized by EcSGA1-catalyzed regioselective acylations of all hydroxyl groups on the sugar unit of unprotected steroidal glycosides (SGs) in the late stage, thereby significantly streamlining the synthetic route towards ASGs and thus forming four monoacylates. The improved cytotoxic activities of 3′-acetylated testosterone17-O-β-glucoside towards seven human tumor cell lines were thus observable.",2018 Oct 1,"['Liu, Ming', 'Kong, Jian-Qiang']",Acta Pharm Sin B,,,False
a14910b8e83f501344835665a3d577dc23f77679,PMC,The microbiome and chronic rhinosinusitis,http://dx.doi.org/10.1016/j.wjorl.2018.08.004,PMC6251963,30506054,CC BY-NC-ND,Chronic rhinosinusitis (CRS) is a multifactorial condition in which the microbiota plays a pathogenic role. The nature of the interaction between the microbiota and the local immune system is very complex and has not been fully elucidated. Recent improvements in the microbiological techniques have greatly advanced our understanding of the complex nature of this interaction. This paper summarizes the current state of the rapidly evolving research on this subject. Defining the nature of the role of the microbiota in CRS is important because of the associated therapeutic implications.,2018 Oct 31,"['Sivasubramaniam, Rahuram', 'Douglas, Richard']",World J Otorhinolaryngol Head Neck Surg,,,False
4a758df0843f5c4f55d49cf8e47098ffcaaa6022,PMC,"Middle East respiratory syndrome coronavirus (MERS-CoV): Impact on Saudi Arabia, 2015",http://dx.doi.org/10.1016/j.sjbs.2016.09.020,PMC6252006,30505188,CC BY-NC-ND,"Middle East respiratory syndrome is the acute respiratory syndrome caused by betacoronavirus MERS-CoV. The first case of this disease was reported from Saudi Arabia in 2012. This virus is lethal and is a close relative of a severe acute respiratory syndrome (SARS), which is responsible for more than 3000 deaths in 2002–2003. According to Ministry of Health, Saudi Arabia. The number of new cases is 457 in 2015. Riyadh has the highest number of reports in comparison to the other cities. According to this report, males are more susceptible than female, especially after the age of 40. Because of the awareness and early diagnosis the incidence is falling gradually. The pre-existence of another disease like cancer or diabetic etc. boosts the infection. MERS is a zoonotic disease and human to human transmission is low. The MERS-CoV is a RNA virus with protein envelope. On the outer surface, virus has spike like glycoprotein which is responsible for the attachment and entrance inside host cells. There is no specific treatment for the MERS-CoV till now, but drugs are in pipeline which bind with the spike glycoprotein and inhibit its entrance host cells. MERS-CoV and SAR-CoV are from the same genus, so it was thought that the drugs which inhibit the growth of SARS-CoV can also inhibit the growth of MERS-CoV but those drugs are not completely inhibiting virus activity. Until we don’t have proper structure and the treatment of MERS-CoV, We should take precautions, especially the health care workers, Camel owners and Pilgrims during Hajj and Umrah, because they are at a higher risk of getting infected.",2018 Nov 1,"Faridi, Uzma",Saudi J Biol Sci,,,False
656804baa38b83efc3fbbc24cbc19b89e6d778f0,PMC,RNA structure interactions and ribonucleoprotein processes of the influenza A virus,http://dx.doi.org/10.1093/bfgp/elx028,PMC6252904,29040388,CC BY-NC,"In one more years, we will ‘celebrate’ an exact centenary of the Spanish flu pandemic. With the rapid evolution of the influenza virus, the possibility of novel pandemic remains ever a concern. This review covers our current knowledge of the influenza A virus: on the role of RNA in translation, replication, what is known of the expressed proteins and the protein products generated from alternative splicing, and on the role of base pairing in RNA structure. We highlight the main events associated with viral entry into the cell, the transcription and replication process, an export of the viral genetic material from the nucleus and the final release of the virus. We discuss the observed potential roles of RNA secondary structure (the RNA base-pairing arrangement) and RNA/RNA interactions in this scheme.",2017 Oct 10,"['Dawson, Wayne K', 'Lazniewski, Michal', 'Plewczynski, Dariusz']",Brief Funct Genomics,,,True
0f462eee8a53108cbdec664ee063f824e750c336,PMC,1583. The Utility of the Immunodeficiency Scoring Index (ISI) to Predict Outcomes of Coronavirus (HCoV) Infections in Hematopietic Cell Transplant (HCT) Recipients,http://dx.doi.org/10.1093/ofid/ofy210.1411,PMC6252950,,CC BY-NC-ND,"BACKGROUND: Respiratory viral infections in HCT recipients are associated with high morbidity and mortality, especially after progression from upper respiratory tract infection (URI) to lower respiratory tract infections (LRI). Data on risk factors (RF) for LRI and mortality is lacking for HCoV infections after HCT. We aimed to validate our ISI in HCoV infections. METHODS: All adult HCT recipients with HCoV infection from 2015 to 2017 were evaluated. An ISI based on RF was used to classify patients as low (0–2), moderate (3–6), or high (7 or higher) risk for progression to LRI or death. We defined LRI as HCoV detected in nasal wash and/or bronchoalveolar lavage and new lung infiltrates on diagnostic imaging. Clinical parameters were collected and ISI were calculated for comparison. RESULTS: A total of 144 adult HCT recipients with 166 episodes of HCoV infections were analyzed. The most common HCoV serotype for LRI and URI was 229E (42.4%) and OC43 (37.6%), respectively, and most patients were infected between November and March each year (Figures 1 and 2). When compared with URI, patients with LRI were more likely in the pre-engraftment period, had multiple respiratory viruses infections, had nosocomially acquired HCoV, required hospitalization, ICU transfer, and mechanical ventilation (all, P < 0.05). Overall mortality rate was 4% at Day 30 from diagnosis and all patients who died had LRI with an 18% mortality. Among those who died, 33% had nosocomial infection, 67% were co-infected with another respiratory virus and 67% required mechanical ventilation. Using an ISI cut off of <4, the negative predictive value (NPV) for progression to LRI was 86% with a specificity of 76%. CONCLUSION: HCT recipients with HCoV LRI were more likely to have a fatal outcome. The NPV of the ISI for progression to LRI was high and could be used as a prognostic tool for future studies and for therapeutic clinical trials. DISCLOSURES: All authors: No reported disclosures.",2018 Nov 26,"['Khawaja, Fareed', 'Shigle, Terri Lynn', 'Ghantoji, Shashank S', 'Batista, Marjorie', 'Ariza-Heredia, Ella', 'Chemaly, Roy F']",Open Forum Infect Dis,,,False
3d8594f91b867a7a54516348f434dd4a950e2aa0,PMC,2264. The Burden of Respiratory Viral Illness in HIV-Infected Patients,http://dx.doi.org/10.1093/ofid/ofy210.1917,PMC6253283,,CC BY-NC-ND,"BACKGROUND: Among individuals living with human immunodeficiency virus (HIV), pulmonary complications are the most frequent cause of morbidity and mortality. Although bacterial and fungal pathogens are well-described etiologies of lung disease, the role of respiratory viruses remains poorly understood. We sought to describe the burden of respiratory viral illness in HIV-infected inpatients admitted to our tertiary care center. METHODS: All HIV-infected inpatients from August 2015 to March 2018 were approached if they presented with respiratory symptoms, defined as cough, dyspnea, sore throat, rhinorrhea, wheezing, or stridor. Eighty patients were enrolled. After obtaining informed consent, nasopharyngeal swabs and blood were collected. If the subject underwent bronchoscopy per the treating physician, excess bronchoalveolar lavage (BAL) sample was collected. Demographic and clinical data were recorded for each subject. Multiplex PCR testing of all respiratory samples was performed. RESULTS: Of the 70 HIV-infected patients that have undergone complete analysis, 23 (33%) tested positive for respiratory viruses. Of these, 11 (48%) were positive for rhinovirus, 3 were positive for influenza A (13%), 2 for parainfluenza 3 (9%), 2 for coronavirus (9%), and one each tested positive for adenovirus, parainfluenza 4, respiratory syncytial virus and influenza B. One patient had co-infection with rhinovirus and human metapneumovirus. Patients infected with a respiratory virus had severe illness as nearly half (10/23; 48%) required intensive care, 5 (22%) required mechanical ventilation, 4 (17%) were discharged to a higher level of care, and 3 (13%) died. CONCLUSION: The role of respiratory viruses on the lung health of HIV-infected patients is poorly defined. In this study, respiratory viruses were identified in over a third of HIV-infected inpatients, representing a substantial disease burden. Moreover, these patients demonstrated significant disease severity. Given these findings, there is a need for future studies of viral infections in HIV-infected individuals to elucidate mechanisms of susceptibility to reduce the burden of pulmonary morbidity in this vulnerable population. DISCLOSURES: All authors: No reported disclosures.",2018 Nov 26,"['Sellers, Subhashini', 'Dover, Kenton', 'Wohl, David Alain', 'Miller, Melissa', 'Dittmer, Dirk', 'Fischer, William']",Open Forum Infect Dis,,,False
cd12e1a41b3b6db301f3ead584f7c369544d5002,PMC,634. Transcriptional Stimulation of Antiviral Response Components by the Structural and Accessory Human coronavirus OC43 Proteins,http://dx.doi.org/10.1093/ofid/ofy210.641,PMC6253624,,CC BY-NC-ND,"BACKGROUND: In Kuwait, human coronavirus OC43 (HCoV-OC43) causes 25–30% of common cold, and 8.8% of respiratory infections in hospitalised patients. It is also associated with severe respiratory symptoms in infants, elderly, and immunocompromised patients. Our previous results showed that the expression of antiviral genes in human embryonic kidney (HEK) 293 cells is downregulated in the presence of HCoV-OC43 proteins. To understand the role of HCoV-OC43 proteins in antagonizing antiviral responses of the host, we investigated the effect of HCoV-OC43 structural and accessory proteins on the transcriptional activation of interferon-stimulated response element (ISRE), interferon-β (IFN-β) promoter, and nuclear factor kappa B response element (NF-kappaB-RE). METHODS: HCoV-OC43 ns2a, ns5a, membrane (M), and nucleocapsid (N) mRNA were amplified and cloned into the pAcGFP1-N expression vector, followed by transfection in HEK-293 cells. Two days post-transfection, the cells were co-transfected with a reporter vector containing firefly luciferase under the control of ISRE, IFN-β promoter, or NF-kappaB-RE. Renilla luciferase vector was used as an internal control for transfection efficiency. Following 24 hours of incubation, the cells were treated with either IFN or tumour necrosis factor (TNF) for 6 hours. Thereafter, promoter activity was assayed using the dual-luciferase reporter assay system. Influenza NS1 protein was used as positive control for antagonism. RESULTS: The transcriptional activity of ISRE, IFN-β promoter, and NF-kappaB-RE was downregulated in the presence of ns2a, ns5a, M, or N protein as there was a sharp fall in firefly luciferase levels. Overall, HCoV-OC43 proteins reduced firefly luciferase levels for ISRE and IFN-β promoter by at least ten fold, whereas for NF-kappaB-RE the firefly luciferase levels were reduced by at least fivefold. CONCLUSION: HCoV-OC43 has the ability to block the activation of different antiviral signaling pathways. DISCLOSURES: All authors: No reported disclosures.",2018 Nov 26,"['Al-Nakib, Widad Widad', 'Beidas, Meshal', 'Chehadeh, Wassim']",Open Forum Infect Dis,,,False
e4bed20a720495dfa13c88678442e2eb8c2ff081,PMC,2518. The Role of Non-Influenza Viruses in the Seasonal Viral Respiratory Illness: A Epidemiologic Study From October 2016–March 2017,http://dx.doi.org/10.1093/ofid/ofy210.2170,PMC6253674,,CC BY-NC-ND,"BACKGROUND: Influenza virus (IV) is a leading cause of morbidity and mortality worldwide; however, understanding the contribution of non-influenza viruses (NIV) to the annual burden of respiratory illnesses (RI) is evolving. Improvements in diagnostic techniques, including the increasing clinical use of respiratory viral PCR panels (vPCR), have markedly advanced our understanding of the contributions of NIV to the “influenza season.” METHODS: A retrospective analysis of all vPCR results from one hospital system, collected between October 1, 2016 and March 7, 2017, including inpatient and outpatient samples was performed. 2,047 vPCR tests were reviewed; after removing those with undetermined results and internal control samples, 1,924 were analyzed. Data points abstracted included detection and identification of virus, and date of detection. We compared the total and monthly rates of NIV with IV, throughout the study period. RESULTS: Of 1,924 vPCR results, 985 (51%) were positive for a respiratory virus. Of these, 302 (31%) were IV, and 683 (69%) were NIV. For every month studied, the ratio of NIV to IV exceeded 50%, including the height of the season. The most commonly detected viruses were Influenza A (30%), Rhino/Enterovirus (24%), RSV (19%), Coronavirus OC43 (7%) and Metapneumovirus (5%). The peak influenza incidence temporally coincided with the national peak months of January and February. The NIV incidence paralleled the trend in IV incidence, dominated by Rhino/Enterovirus and RSV, but without a specific virus driving the trend. CONCLUSION: Non-influenza respiratory viruses cause substantial viral RI during the winter months. Many viral syndromes during the height of influenza season have traditionally been attributed to IV, including influenza-like-illness (ILI); however, these can now be better characterized using patient-specific vPCR panels, leading to improved understanding of NIV epidemiology. Even during the period of highest IV incidence, NIV infections were more common than IV. Understanding the high prevalence of NIV infections may improve the judicious use of both antibiotics and antivirals. There may also be a role for refinement of ILI, including best practices for diagnosis and treatment. DISCLOSURES: All Authors: No reported disclosures.",2018 Nov 26,"['Dean, Chelsea', 'Fitzgibbons, Lynn', 'Li, Jeanne', 'Choe, Jane']",Open Forum Infect Dis,,,False
6b8791fc696da0f017d4c3b92ed3aabc4a470e68,PMC,1241. Surveillance for Viral Respiratory Infections in Pediatric Chronic Care Facilities,http://dx.doi.org/10.1093/ofid/ofy210.1074,PMC6254255,,CC BY-NC-ND,"BACKGROUND: Residents of pediatric chronic care facilities (PCCFs) are vulnerable to acute respiratory infections (ARIs) due to their underlying medical conditions and infection control challenges in congregate living. METHODS: We conducted active, prospective surveillance for ARIs (defined as ≥2 new signs/symptoms of respiratory illness) among all residents in three PCCFs near New York City from December 7, 2016 to May 7, 2017. The parents/guardians of some residents also provided consent for research specimen collection at the start of the study. In that subset, nasopharyngeal swabs were obtained ≤4 days of ARI symptom onset and weekly for 4 weeks of follow-up to assess viral shedding. Influenza, respiratory syncytial virus (RSV), rhinovirus (RV), coronavirus (229E, NL63, OC43, HKU1), parainfluenzavirus (PIV 1–4), metapneumovirus (MPV), adenovirus (AdV), bocavirus (BoV), enterovirus, parechovirus, and M. pneumoniae were tested by the Fast Track Diagnostics Respiratory Pathogens 21 real-time RT-PCR panel. RESULTS: Subset with research specimen collection: Among 79 residents (aged 0–20 years, median = 8), 60 ARIs were reported in 37 (47%) residents. Swabs were obtained at illness onset for 53/60 ARI episodes; among these, there were 25 single-virus detections and five co-detections. An additional 33 single- and five co-detections occurred in 175 follow-up swabs (table). Molecular typing of 32 RV+ specimens identified 13 RV types. All residents: During the 2016–2017 influenza season, 308/322 (96%) age-eligible residents received influenza vaccine and 168/364 (46%) received prophylactic antivirals for influenza exposures. Although influenza was not detected in research swabs, it was detected in 3/200 tests conducted for clinical purposes. CONCLUSION: ARIs were common among residents of three PCCFs, and a variety of respiratory viruses were detected. The rarity of influenza may reflect strong infection control practices in these facilities, including vaccination and prophylactic use of antivirals. DISCLOSURES: All authors: No reported disclosures.",2018 Nov 26,"['Prill, Mila M', 'Kim, Lindsay', 'Wilmont, Sibyl', 'Whitaker, Brett L', 'Lu, Xiaoyan', 'Neu, Natalie', 'Gerber, Susan I', 'Garg, Shikha', 'Stone, Nimalie D', 'Larson, Elaine', 'Saiman, Lisa']",Open Forum Infect Dis,,,False
86396067e3a2f025f33796a205dfec8bfe058fa3,PMC,"724. Neurologic Complications in Hospitalized Pediatric Patients with Influenza Infection, A Multicenter Retrospective Study in Korea",http://dx.doi.org/10.1093/ofid/ofy210.731,PMC6254533,,CC BY-NC-ND,"BACKGROUND: The aim of the study was to evaluate the incidence and characteristics of influenza associated neurologic complications (IANCs) in hospitalized pediatric patients in Korea. METHODS: We performed retrospective review of hospitalized cases of confirmed influenza infection from October 2010 to April 2017. Patient’s data were collected from three referral hospitals in different regions of the country. RESULTS: A total 2,002 laboratory confirmed influenza cases were identified. The median age was 3.3 years old (range 0.0–18.9 years) and 1,003 patients were male (54%). Influenza A was diagnosed in 1,357 cases (68%), influenza B in 624 (31%) and both influenza A and B in 21 (1%). Other combined respiratory virus infection was detected in 104 (5.2%) cases. Out of 2,002 cases, IANCs were identified in 167 cases (8.3%); influenza virus A was detected in 116 (69.4%), B in 50 (29.9%) and both A and B in one case (0.6%). Of 167 cases with IANCs, 25 patients (15%) had underlying neurologic diseases. Eleven patients (11/167, 6.5%) had combined respiratory viral infection (Rhinovirus = 5; respiratory syncytial virus = 3; coronavirus = 2; and bocavirus = 1). The most common diagnosis was a simple febrile seizure (112/167, 67.1%), followed by other seizures (26/167, 15.6%), encephalopathy/encephalitis (17/167, 10.2%), meningitis (7/167, 4.2%), meningism (4/167, 2.4%) and acute ataxia (1/167, 0.6%). In two patients with encephalitis/meningitis, one patient had influenza A and the other patient had influenza B detected by PCR in cerebrospinal fluid. Most of the patients were fully recovered (162/167, 97%) and no neurologic complication occurred in patients who had only initial manifestation of simple febrile seizure. Ten patients (10/167, 6.0%) required hospitalization in intensive care unit. Three patients (3/167, 1.8%) died of encephalopathy (n = 1) and combined encephalopathy/myocarditis (n = 2). Pre-existing neurologic disease was a risk factor of IANCs with an odds ratio of 3.94 (95% confidence interval 2.37 to 6.56, P < 0.0001). CONCLUSION: IANCs is not rare and may cause serious outcome including death. Clinicians should be aware of the increased risk for IANCs in certain patients with neurologic diseases. DISCLOSURES: All authors: No reported disclosures.",2018 Nov 26,"['Choi, Gwang-Jun', 'Park, Ji Young', 'Choi, Joon-Sik', 'Kim, Bitna', 'Choi, Sae Rom', 'Kim, Dong Sub', 'Kang, Ji-Man', 'Lee, Jun Wha', 'Woo, Young-Jong', 'Lee, Jeehun', 'Kim, Yae-Jean']",Open Forum Infect Dis,,,False
6d6294ef224683962e08a1059ea4b027b769e5ed,PMC,"Antiviral and Anti-Inflammatory Activities of Pochonin D, a Heat Shock Protein 90 Inhibitor, against Rhinovirus Infection",http://dx.doi.org/10.4062/biomolther.2017.233,PMC6254639,29715717,CC BY-NC,"Human rhinoviruses (HRV) are one of the major causes of common cold in humans and are also associated with acute asthma and bronchial illness. Heat-shock protein 90 (Hsp90), a molecular chaperone, is an important host factor for the replication of single-strand RNA viruses. In the current study, we examined the effect of the Hsp90 inhibitor pochonin D, in vitro and in vivo, using a murine model of human rhinovirus type 1B (HRV1B) infection. Our data suggested that Hsp90 inhibition significantly reduced the inflammatory cytokine production and lung damage caused by HRV1B infection. The viral titer was significantly lowered in HRV1B-infected lungs and in Hela cells upon treatment with pochonin D. Infiltration of innate immune cells including granulocytes and monocytes was also reduced in the bronchoalveolar lavage (BAL) by pochonin D treatment after HRV1B infection. Histological analysis of the lung and respiratory tract showed that pochonin D protected the mice from HRV1B infection. Collectively, our results suggest that the Hsp90 inhibitor, pochonin D, could be an attractive antiviral therapeutic for treating HRV infection.",2018 Nov 2,"['Song, Jae-Hyoung', 'Shim, Aeri', 'Kim, Yeon-Jeong', 'Ahn, Jae-Hee', 'Kwon, Bo-Eun', 'Pham, Thuy Trang', 'Lee, Jongkook', 'Chang, Sun-Young', 'Ko, Hyun-Jeong']",Biomol Ther (Seoul),,,True
2300246f43291b95cbee7086fd76563e0ad8d380,PMC,"Antiviral and Anti-Inflammatory Activities of Pochonin D, a Heat Shock Protein 90 Inhibitor, against Rhinovirus Infection",http://dx.doi.org/10.4062/biomolther.2017.233,PMC6254639,29715717,CC BY-NC,"Human rhinoviruses (HRV) are one of the major causes of common cold in humans and are also associated with acute asthma and bronchial illness. Heat-shock protein 90 (Hsp90), a molecular chaperone, is an important host factor for the replication of single-strand RNA viruses. In the current study, we examined the effect of the Hsp90 inhibitor pochonin D, in vitro and in vivo, using a murine model of human rhinovirus type 1B (HRV1B) infection. Our data suggested that Hsp90 inhibition significantly reduced the inflammatory cytokine production and lung damage caused by HRV1B infection. The viral titer was significantly lowered in HRV1B-infected lungs and in Hela cells upon treatment with pochonin D. Infiltration of innate immune cells including granulocytes and monocytes was also reduced in the bronchoalveolar lavage (BAL) by pochonin D treatment after HRV1B infection. Histological analysis of the lung and respiratory tract showed that pochonin D protected the mice from HRV1B infection. Collectively, our results suggest that the Hsp90 inhibitor, pochonin D, could be an attractive antiviral therapeutic for treating HRV infection.",2018 Nov 2,"['Song, Jae-Hyoung', 'Shim, Aeri', 'Kim, Yeon-Jeong', 'Ahn, Jae-Hee', 'Kwon, Bo-Eun', 'Pham, Thuy Trang', 'Lee, Jongkook', 'Chang, Sun-Young', 'Ko, Hyun-Jeong']",Biomol Ther (Seoul),,,False
0053afc398e118f91781e815f349804fb05ecfe1,PMC,"Antiviral and Anti-Inflammatory Activities of Pochonin D, a Heat Shock Protein 90 Inhibitor, against Rhinovirus Infection",http://dx.doi.org/10.4062/biomolther.2017.233,PMC6254639,29715717,CC BY-NC,"Human rhinoviruses (HRV) are one of the major causes of common cold in humans and are also associated with acute asthma and bronchial illness. Heat-shock protein 90 (Hsp90), a molecular chaperone, is an important host factor for the replication of single-strand RNA viruses. In the current study, we examined the effect of the Hsp90 inhibitor pochonin D, in vitro and in vivo, using a murine model of human rhinovirus type 1B (HRV1B) infection. Our data suggested that Hsp90 inhibition significantly reduced the inflammatory cytokine production and lung damage caused by HRV1B infection. The viral titer was significantly lowered in HRV1B-infected lungs and in Hela cells upon treatment with pochonin D. Infiltration of innate immune cells including granulocytes and monocytes was also reduced in the bronchoalveolar lavage (BAL) by pochonin D treatment after HRV1B infection. Histological analysis of the lung and respiratory tract showed that pochonin D protected the mice from HRV1B infection. Collectively, our results suggest that the Hsp90 inhibitor, pochonin D, could be an attractive antiviral therapeutic for treating HRV infection.",2018 Nov 2,"['Song, Jae-Hyoung', 'Shim, Aeri', 'Kim, Yeon-Jeong', 'Ahn, Jae-Hee', 'Kwon, Bo-Eun', 'Pham, Thuy Trang', 'Lee, Jongkook', 'Chang, Sun-Young', 'Ko, Hyun-Jeong']",Biomol Ther (Seoul),,,False
3a0c99e76875e3cc05a285d541208ec87adbf383,PMC,"Antiviral and Anti-Inflammatory Activities of Pochonin D, a Heat Shock Protein 90 Inhibitor, against Rhinovirus Infection",http://dx.doi.org/10.4062/biomolther.2017.233,PMC6254639,29715717,CC BY-NC,"Human rhinoviruses (HRV) are one of the major causes of common cold in humans and are also associated with acute asthma and bronchial illness. Heat-shock protein 90 (Hsp90), a molecular chaperone, is an important host factor for the replication of single-strand RNA viruses. In the current study, we examined the effect of the Hsp90 inhibitor pochonin D, in vitro and in vivo, using a murine model of human rhinovirus type 1B (HRV1B) infection. Our data suggested that Hsp90 inhibition significantly reduced the inflammatory cytokine production and lung damage caused by HRV1B infection. The viral titer was significantly lowered in HRV1B-infected lungs and in Hela cells upon treatment with pochonin D. Infiltration of innate immune cells including granulocytes and monocytes was also reduced in the bronchoalveolar lavage (BAL) by pochonin D treatment after HRV1B infection. Histological analysis of the lung and respiratory tract showed that pochonin D protected the mice from HRV1B infection. Collectively, our results suggest that the Hsp90 inhibitor, pochonin D, could be an attractive antiviral therapeutic for treating HRV infection.",2018 Nov 2,"['Song, Jae-Hyoung', 'Shim, Aeri', 'Kim, Yeon-Jeong', 'Ahn, Jae-Hee', 'Kwon, Bo-Eun', 'Pham, Thuy Trang', 'Lee, Jongkook', 'Chang, Sun-Young', 'Ko, Hyun-Jeong']",Biomol Ther (Seoul),,,False
ed94f0bd0fe17c099f8cdff4bf9edbbd29ebf41f,PMC,Structural basis of development of multi-epitope vaccine against Middle East respiratory syndrome using in silico approach,http://dx.doi.org/10.2147/IDR.S175114,PMC6254671,30538505,CC BY-NC,"BACKGROUND: Middle East respiratory syndrome (MERS) is caused by MERS coronavirus (MERS-CoV). Thus far, MERS outbreaks have been reported from Saudi Arabia (2013 and 2014) and South Korea (2015). No specific vaccine has yet been reported against MERS. PURPOSE: To address the urgent need for an MERS vaccine, in the present study, we have designed two multi-epitope vaccines (MEVs) against MERS utilizing several in silico methods and tools. METHODS: The design of both the multi-epitope vaccines (MEVs) are composed of cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) epitopes, screened form thirteen different proteins of MERS-CoV. Both the MEVs also carry potential B-cell linear epitope regions, B-cell discontinuous epitopes as well as interferon-γ-inducing epitopes. Human β-defensin-2 and β-defensin-3 were used as adjuvants to enhance the immune response of MEVs. To design the MEVs, short peptide molecular linkers were utilized to link screened most potential CTL epitopes, HTL epitopes and the adjuvants. Tertiary models for both the MEVs were generated, refined, and further studied for their molecular interaction with toll-like receptor 3. The cDNAs of both MEVs were generated and analyzed in silico for their expression in a mammalian host cell line (human). RESULTS: Screened CTL and HTL epitopes were found to have high propensity for stable molecular interaction with HLA alleles molecules. CTL epitopes were also found to have favorable molecular interaction within the cavity of transporter associated with antigen processing. The selected CTL and HTL epitopes jointly cover upto 94.0% of worldwide human population. Both the CTL and HTL MEVs molecular models have shown to have stable binding and complex formation propensity with toll-like receptor 3. The cDNA analysis of both the MEVs have shown high expression tendency in mammalian host cell line (human). CONCLUSION: After multistage in silico analysis, both the MEVs are predicted to elicit humoral as well as cell mediated immune response. Epitopes of the designed MEVs are predicted to cover large human population worldwide. Hence both the designed MEVs could be tried in vivo as potential vaccine candidates against MERS.",2018 Nov 21,"['Srivastava, Sukrit', 'Kamthania, Mohit', 'Singh, Soni', 'Saxena, Ajay K', 'Sharma, Nishi']",Infect Drug Resist,,,True
fc960b02885e99137c265c8829213604c9945f66,PMC,739. Middle East Respiratory Syndrome Coronavirus Infection Profile in Qatar: A 7-Year Retrospective Study,http://dx.doi.org/10.1093/ofid/ofy210.746,PMC6255065,,CC BY-NC-ND,"BACKGROUND: A deadly zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) had emerged over the last 7 years in the Arabian Peninsula. As of February 28, 2018, 2,182 cases of MERS-CoV infection (with 779 deaths) in 27 countries were reported to WHO worldwide. The objectives of this study were to identify the clinical and epidemiological characteristics of MERS-CoV infection as well as determine its clinical outcome. METHODS: This was a retrospective-observational study of all laboratory confirmed cases of MERS-CoV infection conducted at the main seven hospitals in the State of Qatar from January, 2012 to April 2018. We used the Fast Track diagnostics real-time reverse-transcription polymerase chain reaction (rRT-PCR), targeting the upE and ORF1a genes respectively. Demographics, clinical information, potential contacts and probable risk factors were collected and analyzed by standard statistical methods. RESULTS: The mean annual incidence was 1.7 per 100,0000 person-years. Among the 24 confirmed cases of of MERS-CoV, males constituted the vast majority of cases (23 males) with a median age of 52 years (range 22–74). Fifty percent of the cases were Qatari and 42% reside in the same region. 67% of the cases had contact with camels, and 21% had contact with MERS-CoV-infected patient. Thirty-eight had travel history within 2 weeks of symptoms onset to the Kingdom of Saudi Arabia. Fifty percent were smokers and 42% had comorbidities. The median symptoms duration was 4.5 days. Most of the patient presented with flu-like symptoms, were fever was the most common presentation, followed by cough, SOB, diarrhea, abdominal pain and headache, 96%, 83%, 33%, 8%, 8% and 4%, respectively. All patients were admitted to a tertiary hospital with a median hospital stay 41 days (8–97). Forty-five percent patients developed severe sepsis with multi-organ failure and needed ICU admission. Fifty percent patients developed acute kidney injury, 29% patients were on hemodialysis and 16% needed extra-corporeal membrane oxygenation. Thirty-three percent patients died. The rest of patients had recovered from the infection and discharged home. Among those who died all had one or more comorbidities. CONCLUSION: MERS-CoV infection is a rare infection in the State of Qatar, seen in both Qataris and expatriates with and without travel history. The infection in patients with comorbidities carries high mortality. DISCLOSURES: All authors: No reported disclosures.",2018 Nov 26,"['Elmaki, Nada', 'Abid, Fatma Ben', 'Farag, Elmubasher', 'Alsoub, Hussam', 'Ghazouani, Hafedh Ghazouani', 'Saleh, Mulham Mohed', 'Dousa, Khalid M', 'Al-Khal, Abdullatif', 'Hashim, Samar Mahmoud A', 'Al- Maslamani, Muna']",Open Forum Infect Dis,,,False
445da9fd3c33ca0a37637af5fd029b841ae0daff,PMC,2491. Post-Exposure Prophylaxis With Ribavirin Plus Lopinavir/Ritonavir for Middle East Respiratory Syndrome in Healthcare Workers,http://dx.doi.org/10.1093/ofid/ofy210.2143,PMC6255574,,CC BY-NC-ND,"BACKGROUND: In 2015, an outbreak of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection occurred in South Korea involving 186 patients, 39 of whom were healthcare workers (HCWs) exposed to the infection. An effective post-exposure prophylaxis (PEP) strategy may limit the spread of infection; however, there is no consensus regarding PEP for MERS-CoV infection. In this study, we assessed (1) the efficacy of oral ribavirin and lopinavir/ritonavir as PEP for HCWs exposed to patients with severe MERS-CoV pre-isolation pneumonia, and (2) safety of the PEP regimen. METHODS: We retrospectively enrolled 43 HCWs with high-risk exposure to MERS-CoV from 5 hospitals affected during this outbreak in South Korea. The rate of MERS-CoV infection was compared between 22 workers at 1 hospital who received PEP consisting of oral ribavirin and lopinavir/ritonavir after exposure to patients with severe MERS-CoV pre-isolation pneumonia and 21 workers at other hospitals who did not receive PEP. RESULTS: Six workers (14%) developed MERS-CoV infection; all of these subjects belonged to the non-PEP group. The attack rate was lower in the PEP group compared with the non-PEP group (0% vs. 28.6%; Odds ratio = 0.405, 95% confidence interval = 0.274–0.599; P = 0.009). The most commonly reported side effects of PEP therapy were nausea and diarrhea, but there were no severe adverse effects associated with PEP therapy. CONCLUSION: PEP with a combination of oral ribavirin and lopinavir/ritonavir appears to be effective and generally safe for preventing MERS-CoV infection after high-risk exposure in healthcare workers. DISCLOSURES: All authors: No reported disclosures.",2018 Nov 26,"['Park, So Yeon', 'Lee, Jin Seo', 'Kim, Jungok', 'Joo, Eun-Jeong', 'Eom, Joong Sik', 'Peck, Kyong Ran']",Open Forum Infect Dis,,,False
2ae023dbcedb660475c4de1033343196265fd42c,PMC,Chyloabdomen in a cat with pancreatic carcinoma,http://dx.doi.org/10.4314/ovj.v8i4.16,PMC6258519,30538938,CC BY-NC-SA,"A 12-year-old spayed female domestic shorthair cat was evaluated for a 3-week history of abdominal distension. Chyloabdomen secondary to pancreatic carcinoma was diagnosed. The cat was palliatively managed using rutin and a low-fat diet. The etiology, diagnosis and management of chyloabdomen are discussed.",2018 Nov 24,"['Véran, Emilie', 'Gallay-Lepoutre, Julie', 'Gory, Guillaume', 'Guillaumot, Pierre', 'Duboy, Julie']",Open Vet J,,,True
b16cc9a6b9fa37d7b10f17e8b1d2c6dff8783911,PMC,p53- and ROS-mediated AIF pathway involved in TGEV-induced apoptosis,http://dx.doi.org/10.1292/jvms.18-0104,PMC6261820,30249935,CC BY-NC-ND,"We previously demonstrated that transmissible gastroenteritis virus (TGEV) could induce apoptosis through caspase signaling. However, apoptosis was not completely prevented by caspases inhibitors, suggesting that there may be a caspase-independent pathway involved in TGEV-induced cell apoptosis. In this study, we investigated the regulation of apoptosis-inducing factor (AIF) on TGEV-induced apoptotic pathway. Results indicated that AIF translocated from the mitochondria to nucleus during TGEV infection, and the AIF inhibitor, N-phenylmaleimide (NP), significantly attenuated the apoptosis. In addition, the translocation of AIF was inhibited by Veliparib (ABT-888), an inhibitor of poly (ADP-ribose) polymerase (PARP). And the reactive oxygen species (ROS) scavenger, pyrrolidinedithiocarbamic (PDTC), redistributed AIF in the mitochondria and nucleus in TGEV-infected cells. Moreover, the protein levels in nucleus and the mRNA levels of AIF were inhibited in the presence of the p53 inhibitor, pifithrin-α (PFT-α) or in TGEV-infected p53−/−cells. Furthermore, TGEV-induced apoptosis was blocked by combination of three or more inhibitors, such as pan caspase inhibitor Z-VAD-FMK, NP, ABT-888, PDTC, PFT-α, to treat PK-15 cells. Taken together, these results suggest that the p53- and ROS-mediated AIF pathway and caspase-dependent pathway were involved in TGEV-induced apoptosis.",2018 Nov 25,"['DING, Li', 'LI, Jiawei', 'LI, Weihao', 'FANG, Zhenhua', 'LI, Na', 'WU, Shannan', 'LI, Jiangyue', 'HONG, Meiling']",J Vet Med Sci,,,True
8ab9e9b90aa057cdd59acac5cce30ec1a6784e71,PMC,Detection of neutralizing antibody against porcine epidemic diarrhea virus in subclinically infected finishing pigs,http://dx.doi.org/10.1292/jvms.18-0132,PMC6261828,30282841,CC BY-NC-ND,"The purpose of this study was to detect porcine epidemic diarrhea virus (PEDV) subclinically infected pigs shipped from non-case farms to slaughterhouses. Systematic sampling was conducted at two slaughterhouses. A total of 1,556 blood samples were collected from 80 case and non-case farms from pigs over 6 months old. Blood samples were centrifuged to obtain sera. Serial serum dilutions were subjected to serological examination for PEDV presence using Neutralization test (NT). The cut-off titer was set at titer of 1:2 dilution and farms with at least one positive sample in duplicate were classified as PED-positive farms. Several non-case farms (9.4%, 6/64) and 100% (16/16) of the case farms were indeed positive for PEDV. The proportion of seropositive animals from case farms was 63.7%, significantly different from that of non-case farms (4.3%, P<0.05). In both case and non-case farms, the proportion of seropositive animals in farrow-to-finish farms was significantly higher than in wean-to-finish farms (P<0.05). Seropositive animals in non-case farms were detected by NT in a sero-survey by sampling at slaughterhouses. Therefore, subclinically infected pigs should be considered prior to shipment.",2018 Nov 2,"['KOIKE, Naoki', 'MAI, Thi Ngan', 'SHIRAI, Mamoru', 'KUBO, Meiko', 'HATA, Kazuhiro', 'MARUMOTO, Nobuyuki', 'WATANABE, Shinji', 'SASAKI, Yosuke', 'MITOMA, Shuya', 'NOTSU, Kosuke', 'OKABAYASHI, Tamaki', 'WIRATSUDAKUL, Anuwat', 'KABALI, Emmanuel', 'NORIMINE, Junzo', 'SEKIGUCHI, Satoshi']",J Vet Med Sci,,,True
4476687d4a23df5d5428626f81d9621abf94e679,PMC,Synergistic effect of ribavirin and vaccine for protection during early infection stage of foot-and-mouth disease,http://dx.doi.org/10.4142/jvs.2018.19.6.788,PMC6265586,30304889,CC BY-NC,"In many countries, vaccines are used for the prevention of foot-and-mouth disease (FMD). However, because there is no protection against FMD immediately after vaccination, research and development on antiviral agents is being conducted to induce protection until immunological competence is produced. This study tested whether well-known chemicals used as RNA virus treatment agents had inhibitory effects on FMD viruses (FMDVs) and demonstrated that ribavirin showed antiviral effects against FMDV in vitro/in vivo. In addition, it was observed that combining the administration of the antiviral agents orally and complementary therapy with vaccines synergistically enhanced antiviral activity and preserved the survival rate and body weight in the experimental animals. Antiviral agents mixed with an adjuvant were inoculated intramuscularly along with the vaccines, thereby inhibiting virus replication after injection and verifying that it was possible to induce early protection against viral infection prior to immunity being achieved through the vaccine. Finally, pigs treated with antiviral agents and vaccines showed no clinical signs and had low virus excretion. Based on these results, it is expected that this combined approach could be a therapeutic and preventive treatment for early protection against FMD.",2018 Nov 28,"['Choi, Joo-Hyung', 'Jeong, Kwiwan', 'Kim, Su-Mi', 'Ko, Mi-Kyeong', 'You, Su-Hwa', 'Lyoo, Young S.', 'Kim, Byounghan', 'Ku, Jin-Mo', 'Park, Jong-Hyeon']",J Vet Sci,,,True
464e444443d007ddd7b577c9e878c12eeaf7829e,PMC,ERS syllabus for postgraduate training in respiratory infections: a guide for comprehensive training,http://dx.doi.org/10.1183/20734735.026218,PMC6269171,30519292,CC BY-NC,ERS has developed a syllabus for postgraduate training in respiratory infections to guide programme designers http://ow.ly/xJ0R30m8CYB,2018 Dec,"['Aliberti, Stefano', 'Farr, Amy', 'Tabin, Nathalie', 'Blasi, Francesco', 'Torres, Antoni', 'Woodhead, Mark', 'Migliori, Giovanni Battista', 'Sotgiu, Giovanni', 'Dimopoulos, George', 'Chalmers, James D.', 'Ringshausen, Felix\xa0C.', 'Loebinger, Michael R.', 'Read, Robert', 'Rohde, Gernot']",Breathe (Sheff),,,True
5a0058a8f5c282059a2cc172807b09340161ae77,PMC,Investigation of an experimental infection model of equine coronavirus in adult horses,http://dx.doi.org/10.1111/jvim.15318,PMC6271284,30353949,CC BY-NC,"BACKGROUND: Equine coronavirus (ECoV) is a recently reported enteric disease of adult horses. Natural infection by ECoV has been reported in adult horses worldwide, whereas experimental infection has only been reported in juvenile horses. An experimental infection model is needed to study the clinical presentation, laboratory abnormalities, and pathophysiological changes associated with ECoV. OBJECTIVES: To investigate the clinical, hematologic, molecular, and serological features of adult horses experimentally infected with ECoV. ANIMALS: Eight adult horses. METHODS: Four horses were intragastrically infected with fecal material containing 10(9) genome equivalents of ECoV. Four additional horses were exposed daily to the feces from the experimentally‐infected horses. Monitoring included physical examinations, as well as daily nasal swab, whole blood, and fecal collection for molecular detection of ECoV. Blood was collected every other day for hematologic analysis and weekly for serologic analysis. RESULTS: All 8 horses shed ECoV in feces. Six of the 8 horses (75%) exhibited mild, clinical disease with soft, formed manure; 1 horse exhibited transient pyrexia. All horses maintained total white cell counts within normal limits, but 3 horses developed transient lymphopenia. No statistically significant differences (P = .20) were observed in quantity of fecal shedding of ECoV between the 2 groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Experimental infection of adult horses with ECoV was associated with mild and self‐limiting clinical signs, transient lymphopenia, and fecal shedding of ECoV, which mimics natural infection. No differences between experimentally‐infected horses and horses exposed to ECoV‐containing feces were identified. Results of our study support a fecal‐oral route of transmission.",2018 Oct 24 Nov-Dec,"['Schaefer, Emily', 'Harms, Corey', 'Viner, Molly', 'Barnum, Samantha', 'Pusterla, Nicola']",J Vet Intern Med,,,True
5d76f5faf141941d2f18c2da3b4a518139425316,PMC,"2018 ACVIM Forum Research Report Program: Seattle, Washington, June 14 ‐ 16, 2018",http://dx.doi.org/10.1111/jvim.15314,PMC6272036,,CC BY-NC,,2018 Oct 11 Nov-Dec,,J Vet Intern Med,,,False
35349bb1fc9290338907b7d7f104c9db3951163b,PMC,"2018 ACVIM Forum Research Abstract Program: Seattle, Washington, June 14 ‐ 15, 2018",http://dx.doi.org/10.1111/jvim.15319,PMC6272043,,CC BY-NC,,2018 Oct 25 Nov-Dec,,J Vet Intern Med,,,True
3e880727d0c88f982bad7fa677c2a8dc1d837dc7,PMC,"Knowledge, attitudes, and practices of emergency department staff towards disaster and emergency preparedness at tertiary health care hospital in central Saudi Arabia",http://dx.doi.org/10.15537/smj.2018.11.23026,PMC6274652,30397712,CC BY-NC-SA,"OBJECTIVES: To assess the knowledge, practices, and attitudes regarding disaster and emergency preparedness among Emergency Department (ED) staff. METHODS: This cross-sectional study was conducted at Tertiary health care hospital in central Riyadh, Kingdom of Saudi Arabia. A self-administered survey was utilized to collect data from ED physicians and nurses. The questionnaire was divided into 5 sections viz; demographics, knowledge about disaster management and preparedness, attitudes about disaster planning, current role and practices, and familiarity towards emergency. RESULTS: A 189 participants have completed the questionnaire. Two-third of the participants were below 30 years, and more than 85% were female. One hundred and eleven (58.7%) had a clinical experience of more than 5 years, while 78 (41.3%) participants had more than 3 years of clinical service at the Tertiary care hospital in Riyadh, Kingdom of Saudi Arabia. Correct responses of knowledge towards disaster and emergency preparedness score was 6.2±2.5. Participants with more than 5-years of experience had a statistically significant (p=0.009) knowledge scale score for disaster and emergency preparedness. Overall, 186 (98.4%) patients believed that training is necessary for all healthcare workers. Approximately 153 (81%) participants reported the conduct of disaster drill at their hospital. The mean score (Mean±SD) for the overall familiarity of the study participants with emergency preparedness information questionnaire (EPIQ) scale was 3.2±1.3. CONCLUSION: The level of knowledge was satisfactory among healthcare providers with neutral level of attitude, practice, and familiarity regarding disaster preparedness. Follow-up research is necessary for maximizing ED preparedness.",2018,"['Nofal, Abdullah', 'Alfayyad, Isamme', 'Khan, Anas', 'Aseri, Zohair Al', 'Abu-Shaheen, Amani']",Saudi Med J,,,True
031abff76f2005b80e265698e59561577c8c4175,PMC,Pool of MERS experts for deployment established by WHO’s Regional Office for the Eastern Mediterranean,,PMC6274668,,CC BY-NC-SA,,2018,,Saudi Med J,,,False
6a2d45016115d187120a5c232f671df30422870b,PMC,Nasal microbiota and symptom persistence in acute respiratory tract infections in infants,http://dx.doi.org/10.1183/23120541.00066-2018,PMC6275129,30519565,CC BY-NC,"Acute respiratory tract infections (ARI) in infancy have been implicated in the development of chronic respiratory disease, but the complex interplay between viruses, bacteria and host is not completely understood. We aimed to prospectively determine whether nasal microbiota changes occur between the onset of the first symptomatic ARI in the first year of life and 3 weeks later, and to explore possible associations with the duration of respiratory symptoms, as well as with host, environmental and viral factors. Nasal microbiota of 167 infants were determined at both time-points by 16S ribosomal RNA-encoding gene PCR amplification and subsequent pyrosequencing. Infants were clustered based on their nasal microbiota using hierarchical clustering methods at both time-points. We identified five dominant infant clusters with distinct microbiota at the onset of ARI but only three clusters after 3 weeks. In these three clusters, symptom persistence was overrepresented in the Streptococcaceae-dominated cluster and underrepresented in the cluster dominated by “Others” (p<0.001). Duration of symptoms was not associated with the type of respiratory virus. Infants with prolonged respiratory symptoms after their first ARI tend to exhibit distinct microbial compositions, indicating close microbiota–host interactions that seem to be of importance for symptom persistence and recovery.",2018 Dec 3,"['Neumann, Roland P.', 'Hilty, Markus', 'Xu, Binbin', 'Usemann, Jakob', 'Korten, Insa', 'Mika, Moana', 'Müller, Loretta', 'Latzin, Philipp', 'Frey, Urs']",ERJ Open Res,,,True
81c92759c804f01629de5c8499535a5b300b5f16,PMC,Nasal microbiota and symptom persistence in acute respiratory tract infections in infants,http://dx.doi.org/10.1183/23120541.00066-2018,PMC6275129,30519565,CC BY-NC,"Acute respiratory tract infections (ARI) in infancy have been implicated in the development of chronic respiratory disease, but the complex interplay between viruses, bacteria and host is not completely understood. We aimed to prospectively determine whether nasal microbiota changes occur between the onset of the first symptomatic ARI in the first year of life and 3 weeks later, and to explore possible associations with the duration of respiratory symptoms, as well as with host, environmental and viral factors. Nasal microbiota of 167 infants were determined at both time-points by 16S ribosomal RNA-encoding gene PCR amplification and subsequent pyrosequencing. Infants were clustered based on their nasal microbiota using hierarchical clustering methods at both time-points. We identified five dominant infant clusters with distinct microbiota at the onset of ARI but only three clusters after 3 weeks. In these three clusters, symptom persistence was overrepresented in the Streptococcaceae-dominated cluster and underrepresented in the cluster dominated by “Others” (p<0.001). Duration of symptoms was not associated with the type of respiratory virus. Infants with prolonged respiratory symptoms after their first ARI tend to exhibit distinct microbial compositions, indicating close microbiota–host interactions that seem to be of importance for symptom persistence and recovery.",2018 Dec 3,"['Neumann, Roland P.', 'Hilty, Markus', 'Xu, Binbin', 'Usemann, Jakob', 'Korten, Insa', 'Mika, Moana', 'Müller, Loretta', 'Latzin, Philipp', 'Frey, Urs']",ERJ Open Res,,,True
4b39a22119a35764490e94b64fd908629af5d2f0,PMC,Nasal microbiota and symptom persistence in acute respiratory tract infections in infants,http://dx.doi.org/10.1183/23120541.00066-2018,PMC6275129,30519565,CC BY-NC,"Acute respiratory tract infections (ARI) in infancy have been implicated in the development of chronic respiratory disease, but the complex interplay between viruses, bacteria and host is not completely understood. We aimed to prospectively determine whether nasal microbiota changes occur between the onset of the first symptomatic ARI in the first year of life and 3 weeks later, and to explore possible associations with the duration of respiratory symptoms, as well as with host, environmental and viral factors. Nasal microbiota of 167 infants were determined at both time-points by 16S ribosomal RNA-encoding gene PCR amplification and subsequent pyrosequencing. Infants were clustered based on their nasal microbiota using hierarchical clustering methods at both time-points. We identified five dominant infant clusters with distinct microbiota at the onset of ARI but only three clusters after 3 weeks. In these three clusters, symptom persistence was overrepresented in the Streptococcaceae-dominated cluster and underrepresented in the cluster dominated by “Others” (p<0.001). Duration of symptoms was not associated with the type of respiratory virus. Infants with prolonged respiratory symptoms after their first ARI tend to exhibit distinct microbial compositions, indicating close microbiota–host interactions that seem to be of importance for symptom persistence and recovery.",2018 Dec 3,"['Neumann, Roland P.', 'Hilty, Markus', 'Xu, Binbin', 'Usemann, Jakob', 'Korten, Insa', 'Mika, Moana', 'Müller, Loretta', 'Latzin, Philipp', 'Frey, Urs']",ERJ Open Res,,,False
e5f71ba1a7a42ab454f9db83a9942509eb947fd3,PMC,Nasal microbiota and symptom persistence in acute respiratory tract infections in infants,http://dx.doi.org/10.1183/23120541.00066-2018,PMC6275129,30519565,CC BY-NC,"Acute respiratory tract infections (ARI) in infancy have been implicated in the development of chronic respiratory disease, but the complex interplay between viruses, bacteria and host is not completely understood. We aimed to prospectively determine whether nasal microbiota changes occur between the onset of the first symptomatic ARI in the first year of life and 3 weeks later, and to explore possible associations with the duration of respiratory symptoms, as well as with host, environmental and viral factors. Nasal microbiota of 167 infants were determined at both time-points by 16S ribosomal RNA-encoding gene PCR amplification and subsequent pyrosequencing. Infants were clustered based on their nasal microbiota using hierarchical clustering methods at both time-points. We identified five dominant infant clusters with distinct microbiota at the onset of ARI but only three clusters after 3 weeks. In these three clusters, symptom persistence was overrepresented in the Streptococcaceae-dominated cluster and underrepresented in the cluster dominated by “Others” (p<0.001). Duration of symptoms was not associated with the type of respiratory virus. Infants with prolonged respiratory symptoms after their first ARI tend to exhibit distinct microbial compositions, indicating close microbiota–host interactions that seem to be of importance for symptom persistence and recovery.",2018 Dec 3,"['Neumann, Roland P.', 'Hilty, Markus', 'Xu, Binbin', 'Usemann, Jakob', 'Korten, Insa', 'Mika, Moana', 'Müller, Loretta', 'Latzin, Philipp', 'Frey, Urs']",ERJ Open Res,,,False
42acec8b568d37919600c778f37d025370833e95,PMC,Nasal microbiota and symptom persistence in acute respiratory tract infections in infants,http://dx.doi.org/10.1183/23120541.00066-2018,PMC6275129,30519565,CC BY-NC,"Acute respiratory tract infections (ARI) in infancy have been implicated in the development of chronic respiratory disease, but the complex interplay between viruses, bacteria and host is not completely understood. We aimed to prospectively determine whether nasal microbiota changes occur between the onset of the first symptomatic ARI in the first year of life and 3 weeks later, and to explore possible associations with the duration of respiratory symptoms, as well as with host, environmental and viral factors. Nasal microbiota of 167 infants were determined at both time-points by 16S ribosomal RNA-encoding gene PCR amplification and subsequent pyrosequencing. Infants were clustered based on their nasal microbiota using hierarchical clustering methods at both time-points. We identified five dominant infant clusters with distinct microbiota at the onset of ARI but only three clusters after 3 weeks. In these three clusters, symptom persistence was overrepresented in the Streptococcaceae-dominated cluster and underrepresented in the cluster dominated by “Others” (p<0.001). Duration of symptoms was not associated with the type of respiratory virus. Infants with prolonged respiratory symptoms after their first ARI tend to exhibit distinct microbial compositions, indicating close microbiota–host interactions that seem to be of importance for symptom persistence and recovery.",2018 Dec 3,"['Neumann, Roland P.', 'Hilty, Markus', 'Xu, Binbin', 'Usemann, Jakob', 'Korten, Insa', 'Mika, Moana', 'Müller, Loretta', 'Latzin, Philipp', 'Frey, Urs']",ERJ Open Res,,,False
0773b5fa847a82b3d084dfe0a76d4288c082bd70,PMC,Nasal microbiota and symptom persistence in acute respiratory tract infections in infants,http://dx.doi.org/10.1183/23120541.00066-2018,PMC6275129,30519565,CC BY-NC,"Acute respiratory tract infections (ARI) in infancy have been implicated in the development of chronic respiratory disease, but the complex interplay between viruses, bacteria and host is not completely understood. We aimed to prospectively determine whether nasal microbiota changes occur between the onset of the first symptomatic ARI in the first year of life and 3 weeks later, and to explore possible associations with the duration of respiratory symptoms, as well as with host, environmental and viral factors. Nasal microbiota of 167 infants were determined at both time-points by 16S ribosomal RNA-encoding gene PCR amplification and subsequent pyrosequencing. Infants were clustered based on their nasal microbiota using hierarchical clustering methods at both time-points. We identified five dominant infant clusters with distinct microbiota at the onset of ARI but only three clusters after 3 weeks. In these three clusters, symptom persistence was overrepresented in the Streptococcaceae-dominated cluster and underrepresented in the cluster dominated by “Others” (p<0.001). Duration of symptoms was not associated with the type of respiratory virus. Infants with prolonged respiratory symptoms after their first ARI tend to exhibit distinct microbial compositions, indicating close microbiota–host interactions that seem to be of importance for symptom persistence and recovery.",2018 Dec 3,"['Neumann, Roland P.', 'Hilty, Markus', 'Xu, Binbin', 'Usemann, Jakob', 'Korten, Insa', 'Mika, Moana', 'Müller, Loretta', 'Latzin, Philipp', 'Frey, Urs']",ERJ Open Res,,,False
40234a3a592579ea8fc20b2d256a045b5c57cf41,PMC,Nasal microbiota and symptom persistence in acute respiratory tract infections in infants,http://dx.doi.org/10.1183/23120541.00066-2018,PMC6275129,30519565,CC BY-NC,"Acute respiratory tract infections (ARI) in infancy have been implicated in the development of chronic respiratory disease, but the complex interplay between viruses, bacteria and host is not completely understood. We aimed to prospectively determine whether nasal microbiota changes occur between the onset of the first symptomatic ARI in the first year of life and 3 weeks later, and to explore possible associations with the duration of respiratory symptoms, as well as with host, environmental and viral factors. Nasal microbiota of 167 infants were determined at both time-points by 16S ribosomal RNA-encoding gene PCR amplification and subsequent pyrosequencing. Infants were clustered based on their nasal microbiota using hierarchical clustering methods at both time-points. We identified five dominant infant clusters with distinct microbiota at the onset of ARI but only three clusters after 3 weeks. In these three clusters, symptom persistence was overrepresented in the Streptococcaceae-dominated cluster and underrepresented in the cluster dominated by “Others” (p<0.001). Duration of symptoms was not associated with the type of respiratory virus. Infants with prolonged respiratory symptoms after their first ARI tend to exhibit distinct microbial compositions, indicating close microbiota–host interactions that seem to be of importance for symptom persistence and recovery.",2018 Dec 3,"['Neumann, Roland P.', 'Hilty, Markus', 'Xu, Binbin', 'Usemann, Jakob', 'Korten, Insa', 'Mika, Moana', 'Müller, Loretta', 'Latzin, Philipp', 'Frey, Urs']",ERJ Open Res,,,False
8f3bb5a9bf1d61de95f4caa4f67d250dc4c09dbb,PMC,Nasal microbiota and symptom persistence in acute respiratory tract infections in infants,http://dx.doi.org/10.1183/23120541.00066-2018,PMC6275129,30519565,CC BY-NC,"Acute respiratory tract infections (ARI) in infancy have been implicated in the development of chronic respiratory disease, but the complex interplay between viruses, bacteria and host is not completely understood. We aimed to prospectively determine whether nasal microbiota changes occur between the onset of the first symptomatic ARI in the first year of life and 3 weeks later, and to explore possible associations with the duration of respiratory symptoms, as well as with host, environmental and viral factors. Nasal microbiota of 167 infants were determined at both time-points by 16S ribosomal RNA-encoding gene PCR amplification and subsequent pyrosequencing. Infants were clustered based on their nasal microbiota using hierarchical clustering methods at both time-points. We identified five dominant infant clusters with distinct microbiota at the onset of ARI but only three clusters after 3 weeks. In these three clusters, symptom persistence was overrepresented in the Streptococcaceae-dominated cluster and underrepresented in the cluster dominated by “Others” (p<0.001). Duration of symptoms was not associated with the type of respiratory virus. Infants with prolonged respiratory symptoms after their first ARI tend to exhibit distinct microbial compositions, indicating close microbiota–host interactions that seem to be of importance for symptom persistence and recovery.",2018 Dec 3,"['Neumann, Roland P.', 'Hilty, Markus', 'Xu, Binbin', 'Usemann, Jakob', 'Korten, Insa', 'Mika, Moana', 'Müller, Loretta', 'Latzin, Philipp', 'Frey, Urs']",ERJ Open Res,,,False
3bbc1e3fede8608e7d854bfbd5c3ef7b85010417,PMC,Nasal microbiota and symptom persistence in acute respiratory tract infections in infants,http://dx.doi.org/10.1183/23120541.00066-2018,PMC6275129,30519565,CC BY-NC,"Acute respiratory tract infections (ARI) in infancy have been implicated in the development of chronic respiratory disease, but the complex interplay between viruses, bacteria and host is not completely understood. We aimed to prospectively determine whether nasal microbiota changes occur between the onset of the first symptomatic ARI in the first year of life and 3 weeks later, and to explore possible associations with the duration of respiratory symptoms, as well as with host, environmental and viral factors. Nasal microbiota of 167 infants were determined at both time-points by 16S ribosomal RNA-encoding gene PCR amplification and subsequent pyrosequencing. Infants were clustered based on their nasal microbiota using hierarchical clustering methods at both time-points. We identified five dominant infant clusters with distinct microbiota at the onset of ARI but only three clusters after 3 weeks. In these three clusters, symptom persistence was overrepresented in the Streptococcaceae-dominated cluster and underrepresented in the cluster dominated by “Others” (p<0.001). Duration of symptoms was not associated with the type of respiratory virus. Infants with prolonged respiratory symptoms after their first ARI tend to exhibit distinct microbial compositions, indicating close microbiota–host interactions that seem to be of importance for symptom persistence and recovery.",2018 Dec 3,"['Neumann, Roland P.', 'Hilty, Markus', 'Xu, Binbin', 'Usemann, Jakob', 'Korten, Insa', 'Mika, Moana', 'Müller, Loretta', 'Latzin, Philipp', 'Frey, Urs']",ERJ Open Res,,,False
c0a0552ddfb422b518d3248184c6401c138c2b74,PMC,Nasal microbiota and symptom persistence in acute respiratory tract infections in infants,http://dx.doi.org/10.1183/23120541.00066-2018,PMC6275129,30519565,CC BY-NC,"Acute respiratory tract infections (ARI) in infancy have been implicated in the development of chronic respiratory disease, but the complex interplay between viruses, bacteria and host is not completely understood. We aimed to prospectively determine whether nasal microbiota changes occur between the onset of the first symptomatic ARI in the first year of life and 3 weeks later, and to explore possible associations with the duration of respiratory symptoms, as well as with host, environmental and viral factors. Nasal microbiota of 167 infants were determined at both time-points by 16S ribosomal RNA-encoding gene PCR amplification and subsequent pyrosequencing. Infants were clustered based on their nasal microbiota using hierarchical clustering methods at both time-points. We identified five dominant infant clusters with distinct microbiota at the onset of ARI but only three clusters after 3 weeks. In these three clusters, symptom persistence was overrepresented in the Streptococcaceae-dominated cluster and underrepresented in the cluster dominated by “Others” (p<0.001). Duration of symptoms was not associated with the type of respiratory virus. Infants with prolonged respiratory symptoms after their first ARI tend to exhibit distinct microbial compositions, indicating close microbiota–host interactions that seem to be of importance for symptom persistence and recovery.",2018 Dec 3,"['Neumann, Roland P.', 'Hilty, Markus', 'Xu, Binbin', 'Usemann, Jakob', 'Korten, Insa', 'Mika, Moana', 'Müller, Loretta', 'Latzin, Philipp', 'Frey, Urs']",ERJ Open Res,,,False
e2c392c638380652a5e6bcac9d5600f168f09026,PMC,Nasal microbiota and symptom persistence in acute respiratory tract infections in infants,http://dx.doi.org/10.1183/23120541.00066-2018,PMC6275129,30519565,CC BY-NC,"Acute respiratory tract infections (ARI) in infancy have been implicated in the development of chronic respiratory disease, but the complex interplay between viruses, bacteria and host is not completely understood. We aimed to prospectively determine whether nasal microbiota changes occur between the onset of the first symptomatic ARI in the first year of life and 3 weeks later, and to explore possible associations with the duration of respiratory symptoms, as well as with host, environmental and viral factors. Nasal microbiota of 167 infants were determined at both time-points by 16S ribosomal RNA-encoding gene PCR amplification and subsequent pyrosequencing. Infants were clustered based on their nasal microbiota using hierarchical clustering methods at both time-points. We identified five dominant infant clusters with distinct microbiota at the onset of ARI but only three clusters after 3 weeks. In these three clusters, symptom persistence was overrepresented in the Streptococcaceae-dominated cluster and underrepresented in the cluster dominated by “Others” (p<0.001). Duration of symptoms was not associated with the type of respiratory virus. Infants with prolonged respiratory symptoms after their first ARI tend to exhibit distinct microbial compositions, indicating close microbiota–host interactions that seem to be of importance for symptom persistence and recovery.",2018 Dec 3,"['Neumann, Roland P.', 'Hilty, Markus', 'Xu, Binbin', 'Usemann, Jakob', 'Korten, Insa', 'Mika, Moana', 'Müller, Loretta', 'Latzin, Philipp', 'Frey, Urs']",ERJ Open Res,,,False
c58f3b28b4a61ada287c65f77e6656b88aedaba2,PMC,Nasal microbiota and symptom persistence in acute respiratory tract infections in infants,http://dx.doi.org/10.1183/23120541.00066-2018,PMC6275129,30519565,CC BY-NC,"Acute respiratory tract infections (ARI) in infancy have been implicated in the development of chronic respiratory disease, but the complex interplay between viruses, bacteria and host is not completely understood. We aimed to prospectively determine whether nasal microbiota changes occur between the onset of the first symptomatic ARI in the first year of life and 3 weeks later, and to explore possible associations with the duration of respiratory symptoms, as well as with host, environmental and viral factors. Nasal microbiota of 167 infants were determined at both time-points by 16S ribosomal RNA-encoding gene PCR amplification and subsequent pyrosequencing. Infants were clustered based on their nasal microbiota using hierarchical clustering methods at both time-points. We identified five dominant infant clusters with distinct microbiota at the onset of ARI but only three clusters after 3 weeks. In these three clusters, symptom persistence was overrepresented in the Streptococcaceae-dominated cluster and underrepresented in the cluster dominated by “Others” (p<0.001). Duration of symptoms was not associated with the type of respiratory virus. Infants with prolonged respiratory symptoms after their first ARI tend to exhibit distinct microbial compositions, indicating close microbiota–host interactions that seem to be of importance for symptom persistence and recovery.",2018 Dec 3,"['Neumann, Roland P.', 'Hilty, Markus', 'Xu, Binbin', 'Usemann, Jakob', 'Korten, Insa', 'Mika, Moana', 'Müller, Loretta', 'Latzin, Philipp', 'Frey, Urs']",ERJ Open Res,,,False
645a3eaa114cc4a4827d02c0ef31b8a19c45b802,PMC,"Spectrum of bactericidal action of amylmetacresol/2,4-dichlorobenzyl alcohol lozenges against oropharyngeal organisms implicated in pharyngitis",http://dx.doi.org/10.2147/IJGM.S184406,PMC6276617,30568479,CC BY-NC,"PURPOSE: Pharyngitis is commonly caused by a self-limiting upper respiratory tract infection (URTI) and symptoms typically include sore throat. Antibiotics are often inappropriately used for the treatment of pharyngitis, which can contribute to antimicrobial resistance, therefore non-antibiotic treatments which have broad antiseptic effects may be more appropriate. Amylmetacresol (AMC) and 2,4-dichlorobenzyl alcohol (DCBA) are present in some antiseptic lozenges and have established benefits in providing symptomatic relief and some in vitro antiviral action. METHODS: Seven bacterial species associated with pharyngitis, namely Streptococcus pyogenes, Fusobacterium necrophorum, Streptococcus dysgalactiae subspecies equisimilis, Moraxella catarrhalis, Haemophilus influenza, Arcanobacterium haemolyticum and Staphylococcus aureus, were exposed to an AMC/DCBA lozenge dissolved in artificial saliva. In vitro bactericidal activity was measured as a log reduction in colony-forming units (CFUs). RESULTS: Bactericidal activity was recorded against all organisms after 1 minute. Greater than 3 log(10) reductions in CFUs were observed at 1 minute for S. pyogenes (log(10) reduction CFU/mL ± SD, 5.7±0.1), H. influenza (6.1±0.1), A. haemolyticum (6.5±0.0) and F. necrophorum (6.5±0.0), at 5 minutes for S. dysgalactiae (6.3±0.0) and M. catarrhalis (5.0±0.9) and at 10 minutes for S. aureus (3.5±0.1). CONCLUSION: An AMC/DCBA lozenge demonstrated a greater than 99.9% reduction in CFUs against all tested species within 10 minutes, which is consistent with the time a lozenge remains in the mouth. Patients with uncomplicated bacterial pharyngitis may benefit from the antibacterial action of antiseptic AMC/DCBA lozenges. Furthermore, AMC/DCBA lozenges may be more relevant and appropriate than antibiotics for pharyngitis associated with a self-limiting viral URTI.",2018 Nov 28,"['Matthews, Derek', 'Atkinson, Robert', 'Shephard, Adrian']",Int J Gen Med,,,True
deea74c59b21622d228c43adea5340e8a2447081,PMC,Systems vaccinology and big data in the vaccine development chain,http://dx.doi.org/10.1111/imm.13012,PMC6283655,30317555,CC BY-NC,"Systems vaccinology has proven a fascinating development in the last decade. Where traditionally vaccine development has been dominated by trial and error, systems vaccinology is a tool that provides novel and comprehensive understanding if properly used. Data sets retrieved from systems‐based studies endorse rational design and effective development of safe and efficacious vaccines. In this review we first describe different omics‐techniques that form the pillars of systems vaccinology. In the second part, the application of systems vaccinology in the different stages of vaccine development is described. Overall, this review shows that systems vaccinology has become an important tool anywhere in the vaccine development chain.",2019 Jan 13,"['Raeven, René H. M.', 'van Riet, Elly', 'Meiring, Hugo D.', 'Metz, Bernard', 'Kersten, Gideon F. A.']",Immunology,,,True
d095e5dd57f0cce04d19b803d2eff03b87febf8f,PMC,Overproduction of IL-6 and Type-I IFN in a Lethal Case of Chikungunya Virus Infection in an Elderly Man During the 2017 Italian Outbreak,http://dx.doi.org/10.1093/ofid/ofy276,PMC6284464,30539034,CC BY-NC-ND,"Chikungunya fever is caused by Chikungunya virus (CHIKV) and is generally considered a self-limiting disease. However, severe clinical presentations with a high mortality rate have been reported in association with underlying medical conditions. This study reports the molecular characterization of the virus and an abnormal pattern of circulating cytokines in a unique lethal CHIKV case during the 2017 outbreak in Italy, which involved an elderly patient with underlying cardiac disease. Analysis of inflammatory cytokines revealed a strong increase of interferon (IFN)-α and IFN-β, as well as interleukin-6, suggesting a possible role of type-I IFN in the cytokine storm, which may be correlated with unfavorable prognosis of CHIKV infection.",2018 Oct 25,"['Colavita, Francesca', 'Vita, Serena', 'Lalle, Eleonora', 'Carletti, Fabrizio', 'Bordi, Licia', 'Vincenti, Donatella', 'Pozzetto, Irene', 'Aiuti, Massimo', 'Vairo, Francesco', 'Capobianchi, Maria Rosaria', 'Lichtner, Miriam', 'Castilletti, Concetta']",Open Forum Infect Dis,,,True
46ec3a9b64437b3a7908f0efbf575e1645ee0419,PMC,Porcine Circovirus type 2 – Systemic disease on pig farms and associated knowledge of key players in the pig industry in Central Uganda,http://dx.doi.org/10.1016/j.ijvsm.2018.08.004,PMC6286401,30564593,CC BY-NC-ND,"Porcine Circovirus type 2 (PCV2) infections and associated diseases have been rarely studied in Africa. There is no report of PCV2 infection-associated morbidity and the level of awareness of stakeholders has never been investigated in Uganda. This cross sectional survey investigated the occurrence of Porcine Circovirus type 2 – systemic disease (PCV2-SD) among pigs and the associated level of awareness of stakeholders in Central Uganda. Data were collected using questionnaires, Focus Group Discussions (FGDs), key informant interviews and laboratory investigations. All respondents (n = 131) and farmers attending FGDs (n = 31) had never heard of PCV2-SD and only 16.7% (n = 2) of the interviewed animal health workers (n = 12) knew about the disease. Among the farms, 20 piglets presenting with a chronic wasting and a persistent diarrhea were detected and sampled for laboratory investigations. Severe lymphoid depletion with histiocytic and macrophage infiltration in lymphoid organs (n = 8), shortening of intestinal villi (n = 9), abscesses in various organs (n = 15) and granulomatous pneumonia (n = 2) were the major histopathological lesions described. Immunohistochemistry and PCR assays on organs with implicating lesions confirmed PCV2 infection in 25% (n = 5) of the 20 pigs. The study confirmed the occurrence of PCV2 infections among piglets with persistent diarrhea on pig farms in central Uganda and revealed a low level of associated knowledge among farmers and veterinary practitioners. The study arouses the need for systematic studies on prevalence of PCV2 infections and sensitization of stakeholders on occurrence of PCV2 infections in Uganda.",2018 Aug 28,"['Wilfred, Eneku', 'Mutebi, Francis', 'Mwiine, Frank Norbert', 'James, Okwee-Acai', 'Lonzy, Ojok']",Int J Vet Sci Med,,,False
ad98979eada6e333a276d39efdce21779d538625,PMC,Xanthine-based acyclic nucleoside phosphonates with potent antiviral activity against varicella-zoster virus and human cytomegalovirus,http://dx.doi.org/10.1177/2040206618813050,PMC6287304,30497281,CC BY-NC,"While noncanonic xanthine nucleotides XMP/dXMP play an important role in balancing and maintaining intracellular purine nucleotide pool as well as in potential mutagenesis, surprisingly, acyclic nucleoside phosphonates bearing a xanthine nucleobase have not been studied so far for their antiviral properties. Herein, we report the synthesis of a series of xanthine-based acyclic nucleoside phosphonates and evaluation of their activity against a wide range of DNA and RNA viruses. Two acyclic nucleoside phosphonates within the series, namely 9-[2-(phosphonomethoxy)ethyl]xanthine (PMEX) and 9-[3-hydroxy-2-(phosphonomethoxy)propyl]xanthine (HPMPX), were shown to possess activity against several human herpesviruses. The most potent compound was PMEX, a xanthine analogue of adefovir (PMEA). PMEX exhibited a single digit µM activity against VZV (EC(50) = 2.6 µM, TK(+) Oka strain) and HCMV (EC(50) = 8.5 µM, Davis strain), while its hexadecyloxypropyl monoester derivative was active against HSV-1 and HSV-2 (EC(50) values between 1.8 and 4.0 µM). In contrast to acyclovir, PMEX remained active against the TK(–) VZV 07–1 strain with EC(50) = 4.58 µM. PMEX was suggested to act as an inhibitor of viral DNA polymerase and represents the first reported xanthine-based acyclic nucleoside phosphonate with potent antiviral properties.",2018 Nov 29,"['Baszczyňski, Ondřej', 'Kaiser, Martin Maxmilian', 'Česnek, Michal', 'Břehová, Petra', 'Jansa, Petr', 'Procházková, Eliška', 'Dračínský, Martin', 'Snoeck, Robert', 'Andrei, Graciela', 'Janeba, Zlatko']",Antivir Chem Chemother,,,True
c5c3ad1af37fa848bbdb5fc237c0825aed3a100d,PMC,Successful steroid treatment for acute fibrinous and organizing pneumonia: A case report,http://dx.doi.org/10.12998/wjcc.v6.i15.1053,PMC6288515,30568963,CC BY-NC,"BACKGROUND: Since the acute fibrinous and organizing pneumonia (AFOP) was first described by Beasley in 2002, some case reports of patients aged from 38 d to 80 years have been published worldwide, but there is still no standard therapy for this disease and the treatment methods remain controversial. Both steroid and immunosuppressive agents, such as cyclophosphamide or mycophenolate mofetil, have been reported to be effective in some studies, but with many side effects, especially in patients of advanced age. CASE SUMMARY: We herein report an 81-year-old female patient who was admitted to our hospital due to dry cough, and breathlessness for 1 mo. She was treated with broad-spectrum antibiotics and anti-fungal therapy, but without improvement in both symptoms and radiological findings, and her respiratory status worsened, and she required bed rest almost the whole day. Computed tomography-guided percutaneous needle lung biopsy was performed and histopathology examination confirmed the diagnosis of AFOP. She was then successfully treated with a steroid monotherapy, which resulted in a satisfactory clinical outcome without serious complications. CONCLUSION: We conclude that complete remission of AFOP can be achieved by steroid monotherapy in patients of advanced age.",2018 Dec 6,"['Ning, Ya-Jing', 'Ding, Pei-Shan', 'Ke, Zhang-Yan', 'Zhang, Yan-Bei', 'Liu, Rong-Yu']",World J Clin Cases,,,True
d71ce9edcc0e1fdc375e7aadb23b21aea86ff228,PMC,Host-adapted Cryptosporidium and Enterocytozoon bieneusi genotypes in straw-colored fruit bats in Nigeria,http://dx.doi.org/10.1016/j.ijppaw.2018.12.001,PMC6289945,30560054,CC BY-NC-ND,"Few data are available on the distribution and human infective potential of Cryptosporidium and Enterocytozoon bieneusi genotypes in bats. In this preliminary study, we collected 109 fecal specimens during April–July 2011 from a colony of straw-colored fruit bats (Eidolon helvum) in an urban park (Agodi Gardens) of Ibadan, Nigeria, and analyzed for Cryptosporidium spp., Giardia duodenalis and E. bieneusi using PCR targeting the small subunit rRNA gene, triosephosphate isomerase gene, and ribosomal internal transcribed spacer, respectively. Genotypes of these enteric parasites were determined by DNA sequencing of the PCR products. Altogether, 6 (5.5%), 0 and 16 (14.7%) specimens were positive for Cryptosporidium spp., G. duodenalis, and E. bieneusi, respectively. DNA sequence analysis of the PCR products indicated the presence of two novel Cryptosporidium genotypes named as bat genotype XIV (in 5 specimens) and bat genotype XV (in 1 specimen) and one known E. bieneusi genotype (Type IV in 1 specimen) and two novel E. bieneusi genotypes (Bat1 in 13 specimens and Bat2 in 2 specimens). In phylogenetic analysis of DNA sequences, the two novel Cryptosporidium genotypes were genetically related to Bat genotype II previously identified in fruit bats in China and Philippines, whereas the two novel E. bieneusi genotypes were genetically related to Group 5, which contains several known genotypes from primates. With the exception of Type IV, none of the Cryptosporidium and E. bieneusi genotypes found in bats in this study are known human pathogens. Thus, straw-colored fruit bats in Nigeria are mainly infected with host-adapted Cryptosporidium and E. bieneusi genotypes.",2018 Dec 4,"['Li, Na', 'Ayinmode, Adekunle B.', 'Zhang, Hongwei', 'Feng, Yaoyu', 'Xiao, Lihua']",Int J Parasitol Parasites Wildl,,,False
390dc3c6b8a82c69dddf3395e72846d49f5c4a72,PMC,Measurability of the epidemic reproduction number in data-driven contact networks,http://dx.doi.org/10.1073/pnas.1811115115,PMC6294899,30463945,CC BY-NC-ND,"The basic reproduction number is one of the conceptual cornerstones of mathematical epidemiology. Its classical definition as the number of secondary cases generated by a typical infected individual in a fully susceptible population finds a clear analytical expression in homogeneous and stratified mixing models. Along with the generation time (the interval between primary and secondary cases), the reproduction number allows for the characterization of the dynamics of an epidemic. A clear-cut theoretical picture, however, is hardly found in real data. Here, we infer from highly detailed sociodemographic data two multiplex contact networks representative of a subset of the Italian and Dutch populations. We then simulate an infection transmission process on these networks accounting for the natural history of influenza and calibrated on empirical epidemiological data. We explicitly measure the reproduction number and generation time, recording all individual-level transmission events. We find that the classical concept of the basic reproduction number is untenable in realistic populations, and it does not provide any conceptual understanding of the epidemic evolution. This departure from the classical theoretical picture is not due to behavioral changes and other exogenous epidemiological determinants. Rather, it can be simply explained by the (clustered) contact structure of the population. Finally, we provide evidence that methodologies aimed at estimating the instantaneous reproduction number can operationally be used to characterize the correct epidemic dynamics from incidence data.",2018 Dec 11,"['Liu, Quan-Hui', 'Ajelli, Marco', 'Aleta, Alberto', 'Merler, Stefano', 'Moreno, Yamir', 'Vespignani, Alessandro']",Proc Natl Acad Sci U S A,,,True
b322c2b004bb384ff72b6da2ee511e6b13792bc7,PMC,Measurability of the epidemic reproduction number in data-driven contact networks,http://dx.doi.org/10.1073/pnas.1811115115,PMC6294899,30463945,CC BY-NC-ND,"The basic reproduction number is one of the conceptual cornerstones of mathematical epidemiology. Its classical definition as the number of secondary cases generated by a typical infected individual in a fully susceptible population finds a clear analytical expression in homogeneous and stratified mixing models. Along with the generation time (the interval between primary and secondary cases), the reproduction number allows for the characterization of the dynamics of an epidemic. A clear-cut theoretical picture, however, is hardly found in real data. Here, we infer from highly detailed sociodemographic data two multiplex contact networks representative of a subset of the Italian and Dutch populations. We then simulate an infection transmission process on these networks accounting for the natural history of influenza and calibrated on empirical epidemiological data. We explicitly measure the reproduction number and generation time, recording all individual-level transmission events. We find that the classical concept of the basic reproduction number is untenable in realistic populations, and it does not provide any conceptual understanding of the epidemic evolution. This departure from the classical theoretical picture is not due to behavioral changes and other exogenous epidemiological determinants. Rather, it can be simply explained by the (clustered) contact structure of the population. Finally, we provide evidence that methodologies aimed at estimating the instantaneous reproduction number can operationally be used to characterize the correct epidemic dynamics from incidence data.",2018 Dec 11,"['Liu, Quan-Hui', 'Ajelli, Marco', 'Aleta, Alberto', 'Merler, Stefano', 'Moreno, Yamir', 'Vespignani, Alessandro']",Proc Natl Acad Sci U S A,,,True
b55c993891c702e7ec32d579fd90f380c3814ab9,PMC,Coronaviruses in Avian Species – Review with Focus on Epidemiology and Diagnosis in Wild Birds,http://dx.doi.org/10.2478/jvetres-2018-0035,PMC6296008,30584600,CC BY-NC-ND,"Coronaviruses (CoVs) are a large group of enveloped viruses with a single-strand RNA genome, which continuously circulate in mammals and birds and pose a threat to livestock, companion animals, and humans. CoVs harboured by avian species are classified to the genera gamma- and deltacoronaviruses. Within the gamma-CoVs the main representative is avian coronavirus, a taxonomic name which includes the highly contagious infectious bronchitis viruses (IBVs) in chickens and similar viruses infecting other domestic birds such as turkeys, guinea fowls, or quails. Additionally, IBVs have been detected in healthy wild birds, demonstrating that they may act as the vector between domestic and free-living birds. Moreover, CoVs other than IBVs, are identified in wild birds, which suggests that wild birds play a key role in the epidemiology of other gammaCoVs and deltaCoVs. Development of molecular techniques has significantly improved knowledge of the prevalence of CoVs in avian species. The methods adopted in monitoring studies of CoVs in different avian species are mainly based on detection of conservative regions within the viral replicase, nucleocapsid genes, and 3’UTR or 5’UTR. The purpose of this review is to summarise recent discoveries in the areas of epidemiology and diagnosis of CoVs in avian species and to understand the role of wild birds in the virus distribution.",2018 Dec 10,"['Miłek, Justyna', 'Blicharz-Domańska, Katarzyna']",J Vet Res,,,True
5ceca9883a0930498d29cdfc09b942f6a9c6bf89,PMC,A Preliminary Study to Determine Comprehensive Research and Development Plans for Promoting Mental Health Services,http://dx.doi.org/10.24171/j.phrp.2018.9.6.05,PMC6296814,30584495,CC BY-NC-ND,"OBJECTIVES: The aim of this study was to analyze research and development projects in mental health services in Korea, using priority evaluation of mental health promotion policies to determine direction of the service. METHODS: An online survey was conducted that targeted experts in the mental health service regarding promotion of mental health in Korea in 2016. The survey was based on 32 policy projects that resulted from 12 strategies according to 4 policy objectives. RESULTS: Analysis of 32 mental health projects were assessed regarding the possibility of technology development success, magnitude of the ripple effect, and necessity of a national response. It was observed that 3 policy projects relevant to suicide, had a high relative priority. This was followed by policies for improvement of health insurance and the medical benefit cost system, and policies for reinforcement of crisis psychological support such as those for disaster victims. CONCLUSION: The prioritization of mental health services should place an emphasis on promotion of a healthy mental lifestyle, rehabilitation support for patients with serious mental illness, and reinforcement of social safety networks for suicide prevention.",2018 Dec,"['Kim, Chul Eung', 'Ko, Young-Mi', 'Lee, Sang-Uk', 'Choi, SungKu', 'Han, Kiwan', 'Park, Se Jin', 'Jo, MinKyung', 'Park, Yu Kyong', 'Lee, Hye Young', 'Park, Subin']",Osong Public Health Res Perspect,,,True
1cfcdcf2a3783b9adba2b091bd50c5d8ac3252ff,PMC,Antiviral efficacy of nanoparticulate vacuolar ATPase inhibitors against influenza virus infection,http://dx.doi.org/10.2147/IJN.S185806,PMC6298390,30587980,CC BY-NC,"BACKGROUND: Influenza virus infections are a major public health concern worldwide. Conventional treatments against the disease are designed to target viral proteins. However, the emergence of viral variants carrying drug-resistant mutations can outpace the development of pathogen-targeting antivirals. Diphyllin and bafilomycin are potent vacuolar ATPase (V-ATPase) inhibitors previously shown to have broad-spectrum antiviral activity. However, their poor water solubility and potential off-target effect limit their clinical application. METHODS: In this study, we report that nanoparticle encapsulation of diphyllin and bafilomycin improves the drugs’ anti-influenza applicability. RESULTS: Using PEG-PLGA diblock copolymers, sub-200 nm diphyllin and bafilomycin nanoparticles were prepared, with encapsulation efficiency of 42% and 100%, respectively. The drug-loaded nanoparticles have sustained drug release kinetics beyond 72 hours and facilitate intracellular drug delivery to two different influenza virus-permissive cell lines. As compared to free drugs, the nanoparticulate V-ATPase inhibitors exhibited lower cytotoxicity and greater in vitro antiviral activity, improving the therapeutic index of diphyllin and bafilomycin by approximately 3 and 5-fold, respectively. In a mouse model of sublethal influenza challenge, treatment with diphyllin nanoparticles resulted in reduced body weight loss and viral titer in the lungs. In addition, following a lethal influenza viral challenge, diphyllin nanoparticle treatment conferred a survival advantage of 33%. CONCLUSIONS: These results demonstrate the potential of the nanoparticulate V-ATPase inhibitors for host-targeted treatment against influenza.",2018 Dec 14,"['Hu, Che-Ming Jack', 'Chen, You-Ting', 'Fang, Zih-Syun', 'Chang, Wei-Shan', 'Chen, Hui-Wen']",Int J Nanomedicine,,,True
005c43980edf3fcc2a4d12ee7ad630ddb651ce6e,PMC,Development of a smartphone-based rapid dual fluorescent diagnostic system for the simultaneous detection of influenza A and H5 subtype in avian influenza A-infected patients,http://dx.doi.org/10.7150/thno.28027,PMC6299699,30613288,CC BY-NC,"Accurate and rapid diagnosis of highly pathogenic avian influenza A H5N1 is of critical importance for the effective clinical management of patients. Here, we developed a rapid and simultaneous detection toolkit for influenza A H5 subtype viruses in human samples based on a bioconjugate of quantum dots (QDs) assembly and a smartphone-based rapid dual fluorescent diagnostic system (SRDFDS). Methods: Two types of QDs were assembled on a latex bead to enhance the detection sensitivity and specificity of influenza A infection (QD580) and H5 subtype (QD650). The dual signals of influenza A and H5 subtype of H5N1-infected patients were detected simultaneously and quantified separately by SRDFDS equipped with two emission filters. Results: Our results showed a high sensitivity of 92.86% (13/14) and 78.57% (11/14), and a specificity of 100% (38/38, P < 0.0001) and 97.37% (37/38) for influenza A and H5 subtype detection, respectively. Conclusion: Therefore, our multiplex QD bioconjugates and SRDFDS-based influenza virus detection toolkit potentially provide accurate and meaningful diagnosis information with improved detection accuracies and sensitivities for H5N1 patients.",2018 Nov 29,"['Yeo, Seon-Ju', 'Kang, Homan', 'Dao, Tung Duy', 'Cuc, Bui Thi', 'Nguyen, Anh Thi Viet', 'Tien, Trinh Thi Thuy', 'Hang, Nguyen Le Khanh', 'Phuong, Hoang Vu Mai', 'Thanh, Le Thi', 'Mai, Le Quynh', 'Rah, Yoonhyuk', 'Yu, Kyoungsik', 'Shin, Ho-Joon', 'Chong, Chom-Kyu', 'Choi, Hak Soo', 'Park, Hyun']",Theranostics,,,True
41d42af9e99779958c80165b6958a1cbeba023a9,PMC,Development of a smartphone-based rapid dual fluorescent diagnostic system for the simultaneous detection of influenza A and H5 subtype in avian influenza A-infected patients,http://dx.doi.org/10.7150/thno.28027,PMC6299699,30613288,CC BY-NC,"Accurate and rapid diagnosis of highly pathogenic avian influenza A H5N1 is of critical importance for the effective clinical management of patients. Here, we developed a rapid and simultaneous detection toolkit for influenza A H5 subtype viruses in human samples based on a bioconjugate of quantum dots (QDs) assembly and a smartphone-based rapid dual fluorescent diagnostic system (SRDFDS). Methods: Two types of QDs were assembled on a latex bead to enhance the detection sensitivity and specificity of influenza A infection (QD580) and H5 subtype (QD650). The dual signals of influenza A and H5 subtype of H5N1-infected patients were detected simultaneously and quantified separately by SRDFDS equipped with two emission filters. Results: Our results showed a high sensitivity of 92.86% (13/14) and 78.57% (11/14), and a specificity of 100% (38/38, P < 0.0001) and 97.37% (37/38) for influenza A and H5 subtype detection, respectively. Conclusion: Therefore, our multiplex QD bioconjugates and SRDFDS-based influenza virus detection toolkit potentially provide accurate and meaningful diagnosis information with improved detection accuracies and sensitivities for H5N1 patients.",2018 Nov 29,"['Yeo, Seon-Ju', 'Kang, Homan', 'Dao, Tung Duy', 'Cuc, Bui Thi', 'Nguyen, Anh Thi Viet', 'Tien, Trinh Thi Thuy', 'Hang, Nguyen Le Khanh', 'Phuong, Hoang Vu Mai', 'Thanh, Le Thi', 'Mai, Le Quynh', 'Rah, Yoonhyuk', 'Yu, Kyoungsik', 'Shin, Ho-Joon', 'Chong, Chom-Kyu', 'Choi, Hak Soo', 'Park, Hyun']",Theranostics,,,True
64531e8dca54414b55f67981cd6e67b77fe8c43c,PMC,Immunohistochemical studies on meningoencephalitis in feline infectious peritonitis (FIP),http://dx.doi.org/10.1292/jvms.18-0406,PMC6305510,30333381,CC BY-NC-ND,"The present study describes the association between inflammatory cell types and feline infectious peritonitis virus (FIPV) antigen in the brain of 4 cats diagnosed as feline infectious peritonitis (FIP). Immunohistochemically, FIPV antigens were detected in the inflammatory foci of the leptomeninges, choroid plexus and ventricles in 3 of the 4 cats. In 3 cases, inflammatory foci mainly consisted of CD204- and Iba1-positive macrophages, and the FIPV antigens were found in the macrophages. In the other case which was negative for FIPV antigen, severe inflammation predominantly consisting of CD20-positive B lymphocytes was observed in the leptomeninges and subventricles, accompanied with diffuse proliferation of gemistocytic astrocytes. The difference in histopathology may reflect the inflammatory process or the strain variation of FIP virus.",2018 Dec 17,"['WANG, Huanan', 'HIRABAYASHI, Miyuki', 'CHAMBERS, James K.', 'UCHIDA, Kazuyuki', 'NAKAYAMA, Hiroyuki']",J Vet Med Sci,,,True
fac6a0008107bdbd3d6e609f613ea7b59288e36c,PMC,End-stage Renal Disease and Risk of Active Tuberculosis: a Nationwide Population-Based Cohort Study,http://dx.doi.org/10.3346/jkms.2018.33.e341,PMC6306323,30595682,CC BY-NC,"BACKGROUND: The converging epidemics of tuberculosis (TB) and end-stage renal disease (ESRD) have generated a significant public health burden, however, previous studies have been limited to a small number of patients. This nationwide cohort study aimed to assess the rate of developing active TB among patients receiving dialysis for ESRD. METHODS: The Korean national health insurance database was used to identify patients receiving dialysis for new-onset ESRD during 2004–2013, who were propensity score matched to an equivalent number of non-dialysis subjects from the general population. The incidences of active TB in the ESRD and control cohorts were calculated for 2004–2013, and multivariable Cox proportional hazards model was used to evaluate the ESRD-related risk of active TB. RESULTS: During 2004–2013, 59,584 patients received dialysis for newly diagnosed ESRD. In the dialysis and control cohorts, 457 (0.8%) and 125 (0.2%) cases of active TB were detected, respectively. Patients with ESRD were associated with a significantly higher risk of active TB compared to the controls (incidence rate ratio, 4.80). The ESRD cohort had an independently elevated risk of active TB (adjusted hazard ratio, 4.39; 95% confidence interval, 3.60–5.37). CONCLUSION: We found that patients receiving dialysis for ESRD had an elevated risk of active TB. These results highlight the need for detailed and well-organised guidelines for active TB screening among patients with ESRD.",2018 Dec 13,"['Min, Jinsoo', 'Kwon, Soon Kil', 'Jeong, Hye Won', 'Han, Joung-Ho', 'Kim, Yeonkook Joseph', 'Kang, Minseok', 'Kang, Gilwon']",J Korean Med Sci,,,True
b1e4e816bbe16c3dd36ffdead29d576677983864,PMC,Considering Revision the Criteria for Patients under Investigations for MERS-CoV Infections: Diarrhea or Not,http://dx.doi.org/10.3346/jkms.2018.33.e344,PMC6306324,30595685,CC BY-NC,,2018 Dec 14,"['Kim, Mi-Na', 'Kim, Eui-Chong']",J Korean Med Sci,,,True
cbc7ee25347acd1ad2fef88420dca328d27d8f5d,PMC,"An Atypical Case of Middle East Respiratory Syndrome in a Returning Traveler to Korea from Kuwait, 2018",http://dx.doi.org/10.3346/jkms.2018.33.e348,PMC6306328,30595687,CC BY-NC,"We report a case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in a 61-year-old businessman returning from Kuwait. The patient arrived there on August 16, 2018, developed watery diarrhea on August 28 (day 0), and came back to Korea on September 7 (day 10) as his condition worsened. Upon arrival, he complained of diarrhea and weakness, but denied any respiratory symptoms, and he directly went to visit an emergency room. Chest radiography revealed interstitial infiltrates in the lungs, and he was immediately transferred to an isolation unit. Quantitative real-time PCR analysis of sputum samples taken on day 11 returned positive for MERS-CoV. No secondary MERS-CoV infection was identified among people who had close contact with him. This case underscores the importance of a high index of suspicion of MERS-CoV infection in any febrile patients who present after a trip to the Middle East.",2018 Dec 20,"['Bak, Song Lee', 'Jun, Kang Il', 'Jung, Jongtak', 'Kim, Jeong-Han', 'Kang, Chang Kyung', 'Park, Wan Beom', 'Kim, Nam-Joong', 'Oh, Myoung-don']",J Korean Med Sci,,,True
945fac2c9ade4e451cc0cb8388cf9de8b2f00a47,PMC,"Clinical Features, Severity, and Incidence of RSV Illness During 12 Consecutive Seasons in a Community Cohort of Adults ≥60 Years Old",http://dx.doi.org/10.1093/ofid/ofy316,PMC6306566,30619907,CC BY-NC-ND,"BACKGROUND: The epidemiology and burden of respiratory syncytial virus (RSV) illness are not well defined in older adults. METHODS: Adults ≥60 years old seeking outpatient care for acute respiratory illness were recruited from 2004–2005 through 2015–2016 during the winter seasons. RSV was identified from respiratory swabs by multiplex polymerase chain reaction. Clinical characteristics and outcomes were ascertained by interview and medical record abstraction. The incidence of medically attended RSV was estimated for each seasonal cohort. RESULTS: RSV was identified in 243 (11%) of 2257 enrollments (241 of 1832 individuals), including 121 RSV type A and 122 RSV type B. The RSV clinical outcome was serious in 47 (19%), moderate in 155 (64%), and mild in 41 (17%). Serious outcomes included hospital admission (n = 29), emergency department visit (n = 13), and pneumonia (n = 23) and were associated with lower respiratory tract symptoms during the enrollment visit. Moderate outcomes included receipt of a new antibiotic prescription (n = 144; 59%), bronchodilator/nebulizer (n = 45; 19%), or systemic corticosteroids (n = 28; 12%). The relative risk of a serious outcome was significantly increased in persons aged ≥75 years (vs 60–64 years) and in those with chronic obstructive pulmonary disease or congestive heart failure. The average seasonal incidence was 139 cases/10 000, and it was significantly higher in persons with cardiopulmonary disease compared with others (rate ratio, 1.89; 95% confidence interval, 1.44–2.48). CONCLUSIONS: RSV causes substantial outpatient illness with lower respiratory tract involvement. Serious outcomes are common in older patients and those with cardiopulmonary disease.",2018 Nov 27,"['Belongia, Edward A', 'King, Jennifer P', 'Kieke, Burney A', 'Pluta, Joanna', 'Al-Hilli, Ali', 'Meece, Jennifer K', 'Shinde, Vivek']",Open Forum Infect Dis,,,True
8b3f1411a204bf1cd829342b87e5fa88bb9f12ed,PMC,"Mandatory meningococcal vaccine, and other recommended immunisations: Uptake, barriers, and facilitators among health care workers and trainees at Hajj",http://dx.doi.org/10.12998/wjcc.v6.i16.1128,PMC6306626,30613671,CC BY-NC,"AIM: To evaluate the uptake of a mandatory meningococcal, a highly recommended influenza, and an optional pneumococcal vaccine, and to explore the key factors affecting vaccination rate among health care workers (HCWs) during the Hajj. METHODS: An anonymous cross-sectional online survey was distributed among HCWs and trainees who worked or volunteered at the Hajj 2015-2017 through their line managers, or by visiting their hospitals and healthcare centres in Makkah and Mina. Overseas HCWs who accompanied the pilgrims or those who work in foreign Hajj medical missions were excluded. Pearson’s χ(2) test was used to compare categorical variables and odds ratio (OR) was calculated by “risk estimate” statistics along with 95% confidence interval (95%CI). RESULTS: A total of 138 respondents aged 20 to 59 (median 25.6) years with a male to female ratio of 2.5:1 participated in the survey. Only 11.6% (16/138) participants reported receiving all three vaccines, 15.2% (21/138) did not receive any vaccine, 76.1% (105/138) received meningococcal, 68.1% (94/138) influenza and 13.8% (19/138) pneumococcal vaccine. Females were more likely to receive a vaccine than males (OR 3.6, 95%CI: 1.0-12.7, P < 0.05). Willingness to follow health authority’s recommendation was the main reason for receipt of vaccine (78.8%) while believing that they were up-to-date with vaccination (39.8%) was the prime reason for non-receipt. CONCLUSION: Some HCWs at Hajj miss out the compulsory and highly recommended vaccines; lack of awareness is a key barrier and authority’s advice is an important motivator. Health education followed by stringent measures may be required to improve their vaccination rate.",2018 Dec 26,"['Badahdah, Al-Mamoon', 'Alfelali, Mohammad', 'Alqahtani, Amani S', 'Alsharif, Saeed', 'Barasheed, Osamah', 'Rashid, Harunor', None]",World J Clin Cases,,,True
8c6f071d6b3d84c8f81fe4c6676a1888f58938f1,PMC,Crazy paving pattern as a rare radiological manifestation of peripheral T-cell lymphoma (PTCL) with lung involvement: A case report,http://dx.doi.org/10.1016/j.rmcr.2018.09.015,PMC6308371,30596008,CC BY-NC-ND,"We report on a 70-year old woman with dyspnea, systemic lymphadenopathy and abnormal chest computed tomography (CT) findings. A complete laboratory testing as well as mediastinal tissue sampling via Endobronchial Ultrasound (EBUS)-guided Transbronchial Needle Biopsy (TBNB) did not reveal a definite diagnosis. After experiencing acute respiratory failure which led to intensive care unit, the patient underwent a cervical lymph node biopsy which revealed peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). A CT-guided trans-thoracic lung biopsy was performed that showed involvement of the lung parenchyma in the context of PTCL-NOS. Lung involvement is a rare extra-nodal manifestation of PTCL. The imaging patterns of this lymphoma have not been well described. We conclude that the finding of crazy paving pattern is a rare manifestation of this disease. In patients with pre-existing lymphoma, lung involvement should be included in the differential due to high pre-test probability.",2018 Sep 26,"['Gomatou, Georgia', 'Tzilas, Vasilios', 'Kourti, Georgia', 'Lagou, Styliani', 'Bouros, Demosthenes', 'Syrigos, Konstantinos']",Respir Med Case Rep,,,False
5b25c21a882848393a88f2036871db32f76c7a80,PMC,Construction and next-generation sequencing analysis of a large phage-displayed V(NAR) single-domain antibody library from six naïve nurse sharks,http://dx.doi.org/10.1093/abt/tby011,PMC6312525,30627698,CC BY-NC,"BACKGROUND: Shark new antigen receptor variable domain (V(NAR)) antibodies can bind restricted epitopes that may be inaccessible to conventional antibodies. METHODS: Here, we developed a library construction method based on polymerase chain reaction (PCR)-Extension Assembly and Self-Ligation (named “EASeL”) to construct a large V(NAR) antibody library with a size of 1.2 × 10(10) from six naïve adult nurse sharks (Ginglymostoma cirratum). RESULTS: The next-generation sequencing analysis of 1.19 million full-length V(NAR)s revealed that this library is highly diversified because it covers all four classical V(NAR) types (Types I–IV) including 11% of classical Type I and 57% of classical Type II. About 30% of the total V(NAR)s could not be categorized as any of the classical types. The high variability of complementarity determining region (CDR) 3 length and cysteine numbers are important for the diversity of V(NAR)s. To validate the use of the shark V(NAR) library for antibody discovery, we isolated a panel of V(NAR) phage binders to cancer therapy-related antigens, including glypican-3, human epidermal growth factor receptor 2 (HER2), and programmed cell death-1 (PD1). Additionally, we identified binders to viral antigens that included the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) spike proteins. The isolated shark single-domain antibodies including Type I and Type II V(NAR)s were produced in Escherichia coli and validated for their antigen binding. A Type II V(NAR) (PE38-B6) has a high affinity (K(d) = 10.1 nM) for its antigen. CONCLUSIONS: The naïve nurse shark V(NAR) library is a useful source for isolating single-domain antibodies to a wide range of antigens. The EASeL method may be applicable to the construction of other large diversity gene expression libraries.",2019 Jan 7,"['Feng, Mingqian', 'Bian, Hejiao', 'Wu, Xiaolin', 'Fu, Tianyun', 'Fu, Ying', 'Hong, Jessica', 'Fleming, Bryan D', 'Flajnik, Martin F', 'Ho, Mitchell']",Antib Ther,,,True
fe2b70a4317057c021120d2281f2d7796c742e86,PMC,Inhibition of Triggering Receptor Expressed on Myeloid Cells 1 Ameliorates Inflammation and Macrophage and Neutrophil Activation in Alcoholic Liver Disease in Mice,http://dx.doi.org/10.1002/hep4.1269,PMC6312652,30619998,CC BY-NC-ND,"Alcoholic liver disease (ALD) is characterized by macrophage and neutrophil leukocyte recruitment and activation in the liver. Damage‐ and pathogen‐associated molecular patterns contribute to a self‐perpetuating proinflammatory state in ALD. Triggering receptor expressed on myeloid cells 1 (TREM‐1) is a surface receptor that amplifies inflammation induced by toll‐like receptors (TLRs) and is expressed on neutrophils and monocytes/macrophages. We hypothesized that TREM‐1 signaling contributes to proinflammatory pathway activation in ALD. Using an in vivo ALD model in mice, we tested the effects of ligand‐independent TREM‐1 inhibitory peptides that were formulated into human high‐density lipoprotein (HDL)‐mimicking complexes GF9‐HDL and GA/E31‐HDL. As revealed in vitro, macrophages endocytosed these rationally designed complexes through scavenger receptors. A 5‐week alcohol feeding with the Lieber‐DeCarli diet in mice resulted in increased serum alanine aminotransferase (ALT), liver steatosis, and increased proinflammatory cytokines in the liver. TREM‐1 messenger RNA (mRNA) expression was significantly increased in alcohol‐fed mice, and TREM‐1 inhibitors significantly reduced this increase. TREM‐1 inhibition significantly attenuated alcohol‐induced spleen tyrosine kinase (SYK) activation, an early event in both TLR4 and TREM‐1 signaling. The TREM‐1 inhibitors significantly inhibited macrophage (epidermal growth factor‐like module‐containing mucin‐like hormone receptor‐like 1 [F4/80], clusters of differentiation [CD]68) and neutrophil (lymphocyte antigen 6 complex, locus G [Ly6G] and myeloperoxidase [MPO]) markers and proinflammatory cytokines (monocyte chemoattractant protein 1 [MCP‐1], tumor necrosis factor α [TNF‐α], interleukin‐1β [IL‐1β], macrophage inflammatory protein 1α [MIP‐1α]) at the mRNA level compared to the HDL vehicle. Administration of TREM‐1 inhibitors ameliorated liver steatosis and early fibrosis markers (α‐smooth muscle actin [αSMA] and procollagen1α [Pro‐Col1α]) at the mRNA level in alcohol‐fed mice. However, the HDL vehicle also reduced serum ALT and some cytokine protein levels in alcohol‐fed mice, indicating HDL‐related effects. Conclusion: HDL‐delivered novel TREM‐1 peptide inhibitors ameliorate early phases of inflammation and neutrophil and macrophage recruitment and activation in the liver and attenuate hepatocyte damage and liver steatosis. TREM‐1 inhibition represents a promising therapeutic approach for further investigations in ALD.",2018 Oct 29,"['Tornai, David', 'Furi, Istvan', 'Shen, Zu T.', 'Sigalov, Alexander B.', 'Coban, Sahin', 'Szabo, Gyongyi']",Hepatol Commun,,,True
9d38da02529d9d374d0083040dff52cf993e8285,PMC,GeneOne Life Science,http://dx.doi.org/10.1080/21645515.2018.1507374,PMC6314400,30346869,CC BY-NC-ND,,2018 Oct 26,"Maslow, Joel",Hum Vaccin Immunother,,,False
6d50402d52c9af24a8b2bc012c33116a7ccabdf3,PMC,"Relatedness of the incidence decay with exponential adjustment (IDEA) model, “Farr's law” and SIR compartmental difference equation models",http://dx.doi.org/10.1016/j.idm.2018.03.001,PMC6326218,30839910,CC BY-NC-ND,"Mathematical models are often regarded as recent innovations in the description and analysis of infectious disease outbreaks and epidemics, but simple mathematical expressions have been in use for projection of epidemic trajectories for more than a century. We recently introduced a single equation model (the incidence decay with exponential adjustment, or IDEA model) that can be used for short-term epidemiological forecasting. In the mid-19th century, Dr. William Farr made the observation that epidemic events rise and fall in a roughly symmetrical pattern that can be approximated by a bell-shaped curve. He noticed that this time-evolution behavior could be captured by a single mathematical formula (“Farr's law”) that could be used for epidemic forecasting. We show here that the IDEA model follows Farr's law, and show that for intuitive assumptions, Farr's Law can be derived from the IDEA model. Moreover, we show that both mathematical approaches, Farr's Law and the IDEA model, resemble solutions of a susceptible-infectious-removed (SIR) compartmental differential-equation model in an asymptotic limit, where the changes of disease transmission respond to control measures, and not only to the depletion of susceptible individuals. This suggests that the concept of the reproduction number [Formula: see text] was implicitly captured in Farr's (pre-microbial era) work, and also suggests that control of epidemics, whether via behavior change or intervention, is as integral to the natural history of epidemics as is the dynamics of disease transmission.",2018 Mar 9,"['Santillana, Mauricio', 'Tuite, Ashleigh', 'Nasserie, Tahmina', 'Fine, Paul', 'Champredon, David', 'Chindelevitch, Leonid', 'Dushoff, Jonathan', 'Fisman, David']",Infect Dis Model,,,False
19e9fcce4b442e7bef53c6cec0aee71a1c565943,PMC,Evaluation of a Carbapenem-Saving Strategy Using Empirical Combination Regimen of Piperacillin-Tazobactam and Amikacin in Hemato-Oncology Patients,http://dx.doi.org/10.3346/jkms.2019.34.e17,PMC6327090,30636947,CC BY-NC,"We implemented a carbapenem-saving strategy in hemato-oncology patients from 2013, using an empirical combination of piperacillin-tazobactam and amikacin for high-risk hemato-oncology patients with febrile neutropenia, who remain hemodynamically unstable > 72 hours despite initial cefepime treatment. All-cause mortality was not different between the two periods (6.54 and 6.57 deaths per 1,000 person-day, P = 0.926). Group 2 carbapenem use significantly decreased after strategy implementation (78.43 vs. 67.43 monthly days of therapy, P = 0.018), while carbapenem-resistant gram-negative bacilli did not show meaningful changes during the study period. Our carbapenem-saving strategy could effectively suppress carbapenem use without an increase of overall mortality.",2019 Jan 4,"['Ko, Jae-Hoon', 'Kim, Si-Ho', 'Kang, Cheol-In', 'Cho, Sun Young', 'Lee, Nam Yong', 'Chung, Doo Ryeon', 'Peck, Kyong Ran', 'Song, Jae-Hoon']",J Korean Med Sci,,,True
b09fe466052873919115ea1da6510a01704c6c3a,PMC,Use of Dipstick Assay and Rapid PCR-DNA Analysis of Nasal Secretions for Diagnosis of Bacterial Sinusitis in Children With Chronic Cough,http://dx.doi.org/10.1177/2152656718821281,PMC6327234,30671281,CC BY-NC,"BACKGROUND: Chronic cough in children is a diagnostic challenge. OBJECTIVE: To discover the utility of nasal dipsticks and polymerase chain reaction (PCR)-DNA analysis in differentiating bacterial sinusitis from other causes of chronic cough and identifying pathogens from the nasal cavity. METHOD: We recruited 22 patients under 15 years of age with cough lasting longer than 4 weeks (group 1), 7 controls with allergic rhinitis (group 2), and 10 controls without respiratory symptoms (group 3). Based on symptoms, the results of nasal secretion assays, and nasal endoscopy, a diagnosis of clinical bacterial sinusitis was made. We identified potential pathogens by quantitative PCR of nasal secretions. RESULTS: Group 1A (cough with clinical bacterial sinusitis n = 10): Eight (80%) patients had bacterial sinusitis associated with dominant potential pathogenic bacteria (PPB): Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Group 1B (cough without clinical bacterial sinusitis n = 12): None had dominant PPB. Group 2 (allergic rhinitis n = 7): None had dominant PPB. Group 3 (asymptomatic n = 10): None had dominant PPB. Twenty to 57% of all groups were colonized with Staphylococcus aureus. Fifty to 70% were colonized with Staphylococcus epidermidis, Corynebacterium pseudodiphtheriticum, and Dolosigranulum pigrum. CONCLUSION: In children with chronic cough, clinicians can utilize a simple and inexpensive nasal secretion dipstick assay for rapid diagnosis of sinusitis and identify PPB by DNA-PCR test for specific antibiotic treatment.",2019 Jan 7,"['Song, Charles', 'Chorath, Jeena', 'Pak, Youngju', 'Redjal, Nasser']",Allergy Rhinol (Providence),,,True
f2286bb839d74a844ed5bd6510eab4137d3920b8,PMC,Respiratory Viral Infections in Children and Adolescents with Hematological Malignancies,http://dx.doi.org/10.4084/MJHID.2019.006,PMC6328038,30671212,CC BY-NC,"BACKGROUND: Despite the introduction of a polymerase chain reaction (PCR) test for the diagnosis of respiratory viral infection (RVI), guidance on the application of this test and the management of RVI in immunocompromised children is lacking. This study evaluated the clinical characteristics of RVI and established strategies for the PCR test in children and adolescents with hematological malignancies. METHODS: This study included children and adolescents with underlying hematological malignancies and respiratory symptoms, in whom a multiplex PCR test was performed. Patients in whom RVI was identified and not identified were categorized into Groups I and II, respectively. Group I was sub-divided into patients with upper and lower respiratory infections. The medical records of the enrolled patients were retrospectively reviewed. RESULTS: A total of 93 respiratory illnesses were included. Group I included 46 (49.5%) cases of RVI, including 31 (67.4%) upper and 15 (32.6%) lower respiratory infections. Rhinovirus (37.0%) was the most common viral pathogen. Significantly more patients in Group I had community-acquired respiratory illnesses (p=0.003) and complained of rhinorrhea (p<0.001) and sputum (p=0.008) than those in Group II. In Group I, significantly more patients with lower respiratory infections had uncontrolled underlying malignancies (p=0.038) and received re-induction or palliative chemotherapy (p=0.006) than those with upper respiratory infections. CONCLUSIONS: A multiplex PCR test should be considered for RVI diagnosis in immunocompromised children and adolescents with respiratory symptoms, especially in those with rhinorrhea or sputum prominent over a cough. The early application of the PCR test in patients with uncontrolled underlying malignancies may improve outcomes.",2019 Jan 1,"['Han, Seung Beom', 'Shin, Ju Ae', 'Kim, Seong koo', 'Lee, Jae Wook', 'Lee, Dong-Gun', 'Chung, Nack-Gyun', 'Cho, Bin', 'Jeong, Dae Chul', 'Kang, Jin Han']",Mediterr J Hematol Infect Dis,,,True
16dd2eb417bbac88ac2235efe705761a57807ae6,PMC,"Strangles, convalescent Streptococcus equi subspecies equi M antibody titers, and presence of complications",http://dx.doi.org/10.1111/jvim.15388,PMC6335513,30520521,CC BY-NC,"BACKGROUND: Streptococcus equi subspecies equi infection elicits M protein antibody titers in equids. Interpretation of titers is not generally accepted. HYPOTHESIS: The magnitude of S. equi M protein (SeM) antibody titer after infection (titer ≥1:12 800) will be useful to monitor for the presence of complications or the risk of development of complications. ANIMALS: Forty‐eight horses on 1 farm involved in strangles outbreak. METHODS: Clinical and observational study. S. equi M protein antibody titers were measured on all horses 8 weeks after infection and select horses 12 and 28 weeks after infection. Horses were categorized: no disease, uncomplicated case, persistent guttural pouch (GP) infection, or complicated cases (metastatic abscesses, purpura hemorrhagica, secondary infections, and dysphagia). Category was compared to titer. RESULTS: Twenty‐eight of 48 (58%) developed clinical signs of S. equi infection. Of those, 11 (39%) had uncomplicated strangles, 9 (21%) had persistent GP infection, 5 (18%) were complicated cases, and 3 (11%) had both persistent GP infection and complications. Thirty‐three percent of horses (16 of 48) had SeM antibody titers ≥1:12 800 eight weeks after infection. Of horses with titers ≥1:12 800, 6 of 16 had evidence of complications. Of complicated cases, 6 of 8 had titers ≥1:12 800. In this outbreak, the sensitivity (75%; 95% CI [confidence interval] 45‐105) for a SeM antibody titer ≥1:12 800 detecting complications was higher than the specificity (43%; 95% CI 23‐64). CONCLUSIONS AND CLINICAL IMPORTANCE: This outbreak demonstrates that SeM antibody titers can be increased after infection (≥1:12 800) in the absence of complications of strangles.",2019 Dec 6 Jan-Feb,"['Delph, Katherine M.', 'Beard, Laurie A.', 'Trimble, Amanda C.', 'Sutter, Maureen E.', 'Timoney, John F.', 'Morrow, Jennifer K.']",J Vet Intern Med,,,True
d6da8802866acb6cd35ee1c4a0ec6c64d06b8345,PMC,SOX2 knockdown inhibits the migration and invasion of basal cell carcinoma cells by targeting the SRPK1-mediated PI3K/AKT signaling pathway,http://dx.doi.org/10.3892/ol.2018.9810,PMC6341784,30675221,CC BY-NC-ND,"Basal cell carcinoma (BCC) is the most common type of human skin cancer, which is driven by the aberrant activation of Hedgehog signaling. Previous evidence indicated that sex determining region Y-box 2 (SOX2) is associated with the tumor metastasis. However, the expression and role of SOX2 in BCC remain unknown. Therefore, the aim of the current study was to analyze the possible mechanism of SOX2 in the progression of BCC. The levels of SOX2 in BCC cells were detected by reverse transcription-quantitative polymerase chain reaction. Transwell assays were also used to determine the migration and invasion of BCC cells. Immunoblotting and immunofluorescence were used for analyzing the role of SOX2 knockdown in the serine-arginine protein kinase 1 (SRPK1)-mediated phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway in BCC cells. The results demonstrated that SOX2 is overexpressed in BCC tissues and cells. In addition, SOX2 knockdown inhibited the migration and invasion of BCC cells, and the epithelial-mesenchymal transition (EMT) progress of BCC cells. It was also observed that SOX2 knockdown decreased SRPK1 expression, which further led to the downregulation of PI3K and AKT expression levels in BCC cells. Furthermore, SRPK1 transfection or PI3K/AKT pathway activation abolished the inhibitory effects of SOX2 knockdown on the migration, invasion and EMT progress of BCC cells. In conclusion, these results indicated that SOX2 may potentially serve as a target for BCC therapy by targeting the SRPK1-mediated PI3K/AKT signaling pathway.",2019 Feb 7,"['Li, Zhuo-Ran', 'Jiang, Yong', 'Hu, Jian-Zhong', 'Chen, Yang', 'Liu, Quan-Zhong']",Oncol Lett,,,True
f5a7b8b5e36fb9c710990a5adbe057fdc1682ec5,PMC,Bacterial and Viral Identification Rate in Acute Exacerbation of Chronic Obstructive Pulmonary Disease in Korea,http://dx.doi.org/10.3349/ymj.2019.60.2.216,PMC6342712,30666844,CC BY-NC,"PURPOSE: The most common cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is respiratory infection. Most studies of bacterial or viral cause in AECOPD have been conducted in Western countries. We investigated bacterial and viral identification rates in AECOPD in Korea. MATERIALS AND METHODS: We reviewed and analyzed medical records of 736 cases of AECOPD at the Korea University Guro Hospital. We analyzed bacterial and viral identification rates and classified infections according to epidemiological factors, such as Global Initiative for Chronic Obstructive Lung Disease stage, mortality, and seasonal variation. RESULTS: The numbers of AECOPD events involving only bacterial identification, only viral identification, bacterial-viral co-identification, and no identification were 200 (27.2%), 159 (21.6%), 107 (14.5%), and 270 (36.7%), respectively. The most common infectious bacteria identified were Pseudomonas aeruginosa (13.0%), Streptococcus pneumoniae (11.4%), and Haemophilus influenzae (5.3%); the most common viruses identified were influenza virus (12.4%), rhinovirus (9.4%), parainfluenza virus (5.2%), and metapneumovirus (4.9%). The bacterial identification rate tended to be higher at more advanced stages of chronic obstructive pulmonary disease (p=0.020 overall, p=0.011 for P. aeruginosa, p=0.048 for S. pneumoniae). Staphylococcus aureus and Klebsiella pneumoniae were identified more in mortality group (p=0.003 for S. aureus, p=0.009 for K. pneumoniae). All viruses were seasonal (i.e., greater prevalence in a particular season; p<0.050). Influenza virus and rhinovirus were mainly identified in the winter, parainfluenza virus in the summer, and metapneumovirus in the spring. CONCLUSION: This information on the epidemiology of respiratory infections in AECOPD will improve the management of AECOPD using antibiotics and other treatments in Korea.",2019 Feb 1,"['Choi, Juwhan', 'Oh, Jee Youn', 'Lee, Young Seok', 'Hur, Gyu Young', 'Lee, Sung Yong', 'Shim, Jae Jeong', 'Kang, Kyung Ho', 'Min, Kyung Hoon']",Yonsei Med J,,,True
0c92f5b237572a3461ae2205a62ba7622c07a6ab,PMC,The Role of CXCR3 in Neurological Diseases,http://dx.doi.org/10.2174/1570159X15666171109161140,PMC6343204,29119926,CC BY-NC,"BACKGROUND: Neurological diseases have become an obvious challenge due to insufficient therapeutic intervention. Therefore, novel drugs for various neurological disorders are in desperate need. Recently, compelling evidence has demon-strated that chemokine receptor CXCR3, which is a G protein-coupled receptor in the CXC chemokine receptor family, may play a pivotal role in the development of neurological diseases. The aim of this review is to provide evidence for the potential of CXCR3 as a therapeutic target for neurological diseases. METHODS: English journal articles that focused on the invovlement of CXCR3 in neurological diseases were searched via PubMed up to May 2017. Moreover, reference lists from identified articles were included for overviews. RESULTS: The expression level of CXCR3 in T cells was significantly elevated in several neurological diseases, including multiple sclerosis (MS), glioma, Alzheimer’s disease (AD), chronic pain, human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and bipolar disorder. CXCR3 antagonists showed therapeutic effects in these neurological diseases. CONCLUSION: These studies provided hard evidence that CXCR3 plays a vital role in the pathogenesis of MS, glioma, AD, chronic pain, HAM/TSP and bipolar disorder. CXCR3 is a crucial molecule in neuroinflammatory and neurodegenerative diseases. It regulates the activation of infiltrating cells and resident immune cells. However, the exact functions of CXCR3 in neurological diseases are inconclusive. Thus, it is important to understand the topic of chemokines and the scope of their ac-tivity in neurological diseases.",2019 Feb,"['Zhou, Ya-Qun', 'Liu, Dai-Qiang', 'Chen, Shu-Ping', 'Sun, Jia', 'Zhou, Xue-Rong', 'Xing, Cui', 'Ye, Da-Wei', 'Tian, Yu-Ke']",Curr Neuropharmacol,,,True
57b88add1645a89614742dc32b0e11922c5f37d2,PMC,ISG20 promotes local tumor immunity and contributes to poor survival in human glioma,http://dx.doi.org/10.1080/2162402X.2018.1534038,PMC6343791,30713788,CC BY-NC-ND,"Recent evidence has confirmed that a mutation of the isocitrate dehydrogenase (IDH) gene occurs early in gliomagenesis and contributes to suppressed immunity. The present study aimed to determine the candidate genes associated with IDH mutation status that could serve as biomarkers of immune suppression for improved prognosis prediction. Clinical information and RNA-seq gene expression data were collected for 932 glioma samples from the CGGA and TCGA databases, and differentially expressed genes in both lower-grade glioma (LGG) and glioblastoma (GBM) samples were identified according to IDH mutation status. Only one gene, interferon-stimulated exonuclease gene 20 (ISG20), with reduced expression in IDH mutant tumors, demonstrated significant prognostic value. ISG20 expression level significantly increased with increasing tumor grade, and its high expression was associated with a poor clinical outcome. Moreover, increased ISG20 expression was associated with increased infiltration of monocyte-derived macrophages and neutrophils, and suppressed adaptive immune response. ISG20 expression was also positively correlated with PD-1, PD-L1, and CTLA4 expression, along with the levels of several chemokines. We conclude that ISG20 is a useful biomarker to identify IDH-mediated immune processes in glioma and may serve as a potential therapeutic target.",2018 Oct 31,"['Gao, Mengqi', 'Lin, Yi', 'Liu, Xing', 'Li, Yiming', 'Zhang, Chuanbao', 'Wang, Zheng', 'Wang, Zhiliang', 'Wang, Yulin', 'Guo, Zongze']",Oncoimmunology,,,True
f55f8738047b91e93738b2cdf2dc4cbcdc0634ff,PMC,Middle East respiratory syndrome coronavirus (MERS-CoV) – Saudi Arabia,,PMC6344663,,CC BY-NC-SA,,2018,,Saudi Med J,,,False
d6bbcc059331dda0ac8c4a897f4d7171d0d1cb99,PMC,Psychological Responses among Humidifier Disinfectant Disaster Victims and Their Families,http://dx.doi.org/10.3346/jkms.2019.34.e29,PMC6345639,30686951,CC BY-NC,"To substantiate psychological symptoms following humidifier disinfectant (HD) disasters, counseling records of 26 victims and 92 family members of victims (45 were bereaved) were analyzed retrospectively. Among the victims, 34.6% had Clinical Global Impression-Severity scores of over 4, which meant they were moderately ill. While anxiety/fear and depression with respiratory symptoms were frequently observed in victims and family members, chronic psychological distress such as alcohol/smoking abuse and insomnia was relatively high in bereaved family members. In conclusion, it is important to provide mental health support for victims and their families, focusing on the characteristic symptoms of each group as well as monetary compensation.",2019 Jan 16,"['Yoo, Seonyoung', 'Sim, Minyoung', 'Choi, Jungwon', 'Jeon, Kyoungsun', 'Shin, Jungha', 'Chung, Seockhoon', 'Hong, Sang-Bum', 'Lee, So-Yeon', 'Hong, Soo-Jong']",J Korean Med Sci,,,True
f2e2f923e6fad608a3d34daf4f0ccaa0e4507c44,PMC,An Uncommon Cause of Spontaneous Pneumomediastinum and Subcutaneous Emphysema,http://dx.doi.org/10.12890/2017_000549,PMC6346762,30755935,CC BY-NC-ND,"A 79-year-old gentleman presented with spontaneous pneumomediastinum and subcutaneous emphysema with pneumonia but no pre-existing lung disease. He presented with a 4-day history of increased shortness of breath, pleuritic chest pain, fevers, and non-productive cough. After 4 days of intravenous antibiotics, the patient developed considerable subcutaneous emphysema and pneumomediastinum. Pneumomediastinum presents most commonly with chest pain, shortness of breath, and subcutaneous emphysema. It has previously been associated with cases of pneumonia but often with rare strains such as P. jirovecii pneumonia in immunocompromised patients. This case highlights spontaneous pneumomediastinum as a rare complication of pneumonia. Treatment of pneumomediastinum is typically conservative, and although options may be limited, aggressive management of any causative factor may be essential in selected cases. LEARNING POINTS: Pneumomediastinum and subcutaneous emphysema are rare complications of pneumonia. Computerised tomography is a valuable diagnostic tool for identifying pneumomediastinum in patients with subcutaneous emphysema. While pneumomediastinum is typically a benign condition, aggressive management may occasionally be required. Evidence regarding use of non-invasive/invasive ventilation remains limited but it may theoretically aggravate any air leakage.",2017 Feb 3,"['Edwards, Michael', 'Ramappa, Arun Jeenahalli']",Eur J Case Rep Intern Med,,,True
e27e8c74a021090c4f54ccfca13646232741638a,PMC,"Antiproliferative and apoptotic activity of glycyrrhizinic acid in MCF-7 human breast cancer cells and evaluation of its effect on cell cycle, cell migration and m-TOR/PI3K/Akt signalling pathway",http://dx.doi.org/10.5114/aoms.2018.79429,PMC6348358,30697268,CC BY-NC-SA,"INTRODUCTION: Glycyrrhizinic acid is a natural product of pharmacological relevance and its anticancer activity against breast cancer cell lines has not been evaluated. Therefore the main purpose of the present study was to investigate the anticancer effects of glycyrrhizinic acid in MCF-7 human breast cancer cells. MATERIAL AND METHODS: The MTT assay was used to evaluate the anticancer effects while a clonogenic assay was used to study its effects on colony formation tendency. Flow cytometry was used to study the effects on cell cycle phase distribution and apoptosis. Western blot assay was used to study changes in protein expression of the m-TOR/PI3K/Akt pathway. RESULTS: The results indicated that glycyrrhizinic acid caused significant (p < 0.01). The growth inhibitory effects MCF-7 human breast cancer cells. The growth inhibitory effects of glycyrrhizinic acid exhibited concentration-dependent as well as time-dependent growth inhibitory trend. Different doses of glycyrrhizinic acid had a tendency to significantly (p < 0.01) inhibit the colony formation tendency of MCF-7 cells. As compared to the control group, glycyrrhizinic acid-treated cells showed a high percentage of apoptotic cells. Cells treated with a 10, 50 and 100 µM dose of glycyrrhizinic acid led to a 24.3%, 41.5% and 82.1% increase in the sub-G1 phase (apoptotic) cells. Glycyrrhizinic acid also led to significant (p < 0.01) inhibition of cell invasion along with downregulation of m-TOR/PI3K/Akt protein expression. CONCLUSIONS: Glycyrrhizinic acid inhibited MCF-7 human breast cancer cell growth and therefore may prove essential lead molecule in the treatment of breast cancer.",2019 Jan 8,"['Zhang, Zhen', 'Feng, Yun', 'Li, Zhen-Yu', 'Cao, Xiao-Zhong']",Arch Med Sci,,,True
f9ec0fcbc2df8fea3210c7db618e70145323c81b,PMC,Improving emergency preparedness and response in the Asia-Pacific,http://dx.doi.org/10.1136/bmjgh-2018-001271,PMC6352770,30775010,CC BY-NC,,2019 Jan 29,"['Marais, Ben J', 'Williams, Stephanie', 'Li, Ailan', 'Ofrin, Roderico', 'Merianos, Angela', 'Negin, Joel', 'Firman, Jenny', 'Davies, Robin', 'Sorrell, Tania']",BMJ Glob Health,,,True
d0445a006b72980b50bccc09a785a688457bbede,PMC,Assessing global preparedness for the next pandemic: development and application of an Epidemic Preparedness Index,http://dx.doi.org/10.1136/bmjgh-2018-001157,PMC6352812,30775006,CC BY-NC,"INTRODUCTION: Robust metrics for national-level preparedness are critical for assessing global resilience to epidemic and pandemic outbreaks. However, existing preparedness assessments focus primarily on public health systems or specific legislative frameworks, and do not measure other essential capacities that enable and support public health preparedness and response. METHODS: We developed an Epidemic Preparedness Index (EPI) to assess national-level preparedness. The EPI is global, covering 188 countries. It consists of five subindices measuring each country’s economic resources, public health communications, infrastructure, public health systems and institutional capacity. To evaluate the construct validity of the EPI, we tested its correlation with proxy measures for preparedness and response capacity, including the timeliness of outbreak detection and reporting, as well as vaccination rates during the 2009 H1N1 influenza pandemic. RESULTS: The most prepared countries were concentrated in Europe and North America, while the least prepared countries clustered in Central and West Africa and Southeast Asia. Better prepared countries were found to report infectious disease outbreaks more quickly and to have vaccinated a larger proportion of their population during the 2009 pandemic. CONCLUSION: The EPI measures a country’s capacity to detect and respond to infectious disease events. Existing tools, such as the Joint External Evaluation (JEE), have been designed to measure preparedness within a country over time. The EPI complements the JEE by providing a holistic view of preparedness and is constructed to support comparative risk assessment between countries. The index can be updated rapidly to generate global estimates of pandemic preparedness that can inform strategy and resource allocation.",2019 Jan 29,"['Oppenheim, Ben', 'Gallivan, Mark', 'Madhav, Nita K', 'Brown, Naor', 'Serhiyenko, Volodymyr', 'Wolfe, Nathan D', 'Ayscue, Patrick']",BMJ Glob Health,,,True
48a5d369de0ea286764a65867a49b61ecb2056a7,PMC,Assessing global preparedness for the next pandemic: development and application of an Epidemic Preparedness Index,http://dx.doi.org/10.1136/bmjgh-2018-001157,PMC6352812,30775006,CC BY-NC,"INTRODUCTION: Robust metrics for national-level preparedness are critical for assessing global resilience to epidemic and pandemic outbreaks. However, existing preparedness assessments focus primarily on public health systems or specific legislative frameworks, and do not measure other essential capacities that enable and support public health preparedness and response. METHODS: We developed an Epidemic Preparedness Index (EPI) to assess national-level preparedness. The EPI is global, covering 188 countries. It consists of five subindices measuring each country’s economic resources, public health communications, infrastructure, public health systems and institutional capacity. To evaluate the construct validity of the EPI, we tested its correlation with proxy measures for preparedness and response capacity, including the timeliness of outbreak detection and reporting, as well as vaccination rates during the 2009 H1N1 influenza pandemic. RESULTS: The most prepared countries were concentrated in Europe and North America, while the least prepared countries clustered in Central and West Africa and Southeast Asia. Better prepared countries were found to report infectious disease outbreaks more quickly and to have vaccinated a larger proportion of their population during the 2009 pandemic. CONCLUSION: The EPI measures a country’s capacity to detect and respond to infectious disease events. Existing tools, such as the Joint External Evaluation (JEE), have been designed to measure preparedness within a country over time. The EPI complements the JEE by providing a holistic view of preparedness and is constructed to support comparative risk assessment between countries. The index can be updated rapidly to generate global estimates of pandemic preparedness that can inform strategy and resource allocation.",2019 Jan 29,"['Oppenheim, Ben', 'Gallivan, Mark', 'Madhav, Nita K', 'Brown, Naor', 'Serhiyenko, Volodymyr', 'Wolfe, Nathan D', 'Ayscue, Patrick']",BMJ Glob Health,,,False
95cf6b3c44e05dc3bf6d1e5e3f912af5a7fa8a36,PMC,An mRNA Vaccine Protects Mice against Multiple Tick-Transmitted Flavivirus Infections,http://dx.doi.org/10.1016/j.celrep.2018.11.082,PMC6353567,30566864,CC BY-NC-ND,"Powassan virus (POWV) is an emerging tick-transmitted flavivirus that circulates in North America and Russia. Up to 5% of deer ticks now test positive for POWV in certain regions of the northern United States. Although POWV infections cause life-threatening encephalitis, there is no vaccine or counter-measure available for prevention or treatment. Here, we developed a lipid nanoparticle (LNP)-encapsulated modified mRNA vaccine encoding the POWV prM and E genes and demonstrated its immunogenicity and efficacy in mice following immunization with one or two doses. The POWV mRNA vaccine induced high titers of neutralizing antibody and sterilizing immunity against lethal challenge with different POWV strains. The mRNA vaccine also induced cross-neutralizing antibodies against multiple other tick-borne flaviviruses and protected mice against the distantly related Langat virus. These data demonstrate the utility of the LNP-mRNA vaccine platform for the development of vaccines with protective activity against multiple flaviviruses.",2018 Dec 18,"['VanBlargan, Laura A.', 'Himansu, Sunny', 'Foreman, Bryant M.', 'Ebel, Gregory D.', 'Pierson, Theodore C.', 'Diamond, Michael S.']",Cell Rep,,,True
652d1892ec99d35a3474afe3fd486f05d0423e05,PMC,An mRNA Vaccine Protects Mice against Multiple Tick-Transmitted Flavivirus Infections,http://dx.doi.org/10.1016/j.celrep.2018.11.082,PMC6353567,30566864,CC BY-NC-ND,"Powassan virus (POWV) is an emerging tick-transmitted flavivirus that circulates in North America and Russia. Up to 5% of deer ticks now test positive for POWV in certain regions of the northern United States. Although POWV infections cause life-threatening encephalitis, there is no vaccine or counter-measure available for prevention or treatment. Here, we developed a lipid nanoparticle (LNP)-encapsulated modified mRNA vaccine encoding the POWV prM and E genes and demonstrated its immunogenicity and efficacy in mice following immunization with one or two doses. The POWV mRNA vaccine induced high titers of neutralizing antibody and sterilizing immunity against lethal challenge with different POWV strains. The mRNA vaccine also induced cross-neutralizing antibodies against multiple other tick-borne flaviviruses and protected mice against the distantly related Langat virus. These data demonstrate the utility of the LNP-mRNA vaccine platform for the development of vaccines with protective activity against multiple flaviviruses.",2018 Dec 18,"['VanBlargan, Laura A.', 'Himansu, Sunny', 'Foreman, Bryant M.', 'Ebel, Gregory D.', 'Pierson, Theodore C.', 'Diamond, Michael S.']",Cell Rep,,,False
2e85e487853731cc083f75a7b86e7649a7e2272c,PMC,An mRNA Vaccine Protects Mice against Multiple Tick-Transmitted Flavivirus Infections,http://dx.doi.org/10.1016/j.celrep.2018.11.082,PMC6353567,30566864,CC BY-NC-ND,"Powassan virus (POWV) is an emerging tick-transmitted flavivirus that circulates in North America and Russia. Up to 5% of deer ticks now test positive for POWV in certain regions of the northern United States. Although POWV infections cause life-threatening encephalitis, there is no vaccine or counter-measure available for prevention or treatment. Here, we developed a lipid nanoparticle (LNP)-encapsulated modified mRNA vaccine encoding the POWV prM and E genes and demonstrated its immunogenicity and efficacy in mice following immunization with one or two doses. The POWV mRNA vaccine induced high titers of neutralizing antibody and sterilizing immunity against lethal challenge with different POWV strains. The mRNA vaccine also induced cross-neutralizing antibodies against multiple other tick-borne flaviviruses and protected mice against the distantly related Langat virus. These data demonstrate the utility of the LNP-mRNA vaccine platform for the development of vaccines with protective activity against multiple flaviviruses.",2018 Dec 18,"['VanBlargan, Laura A.', 'Himansu, Sunny', 'Foreman, Bryant M.', 'Ebel, Gregory D.', 'Pierson, Theodore C.', 'Diamond, Michael S.']",Cell Rep,,,True
0a449e173239afb38816257e1a53811b47bf13f4,PMC,Depression as a Mediator of Chronic Fatigue and Post-Traumatic Stress Symptoms in Middle East Respiratory Syndrome Survivors,http://dx.doi.org/10.30773/pi.2018.10.22.3,PMC6354037,30605995,CC BY-NC,"OBJECTIVE: The relationship among chronic fatigue, depressive symptoms, and post-traumatic stress symptoms (PTSSs) among Middle East respiratory syndrome (MERS) survivors is poorly understood. METHODS: Of 148 survivors who consented to be registered and underwent assessments at 12 months (T1) and 18 months (T2) after the MERS outbreak, 72 (48.65%) were evaluated for chronic fatigue, depressive symptoms, and PTSSs based on the Impact of Event ScaleRevised (IES-R), the Patient Health Questionnaire-9 (PHQ-9), and the Fatigue Severity Scale (FSS). Data from 52 subjects, who completed both assessments, were analyzed using a regression-based serial multiple mediation model (PROCESS Model 6). RESULTS: Bootstrap analyses indicated no direct effects of T1 FSS on T2 IES-R but significant positive indirect effects of T1 FSS on T2 IESR through T1 PHQ-9 and T2 PHQ-9 (B=2.1601, SE=1.3268, 95% confidence interval=0.4250–6.1307). In other words, both T1 PHQ-9 and T2 PHQ-9 fully mediated the relationship between T1 FSS and T2 IES. CONCLUSION: Chronic fatigue 12 months after MERS had indirect effects on prolonged PTSSs 18 months after MERS via persisting depression in MERS survivors. This finding supports the need to promote interventional programs for emerging infectious disease survivors with chronic fatigue to reduce depression and prevent prolonged PTSSs.",2019 Jan 7,"['Lee, So Hee', 'Shin, Hyoung-Shik', 'Park, Hye Yoon', 'Kim, Jeong Lan', 'Lee, Jung Jae', 'Lee, Haewoo', 'Won, Sung-Doo', 'Han, Woori']",Psychiatry Investig,,,True
1aaa45043de59cda6c14acd355518c688f37b374,PMC,Ebola Emergency Preparedness: Simulation Training for Frontline Health Care Professionals,http://dx.doi.org/10.15766/mep_2374-8265.10433,PMC6354722,30800728,CC BY-NC-SA,"INTRODUCTION: At Brigham and Women's Hospital, we identified the need for a comprehensive training program designed to prepare frontline staff to safely manage a patient with Ebola viral disease (EVD). The primary goal of this program was to ensure the safety of staff, patients, and the general public by training staff in the correct use of personal protective equipment (PPE) before, during, and after care of patients with EVD. METHODS: We delivered a 4-hour experiential training program to frontline health care professionals who would be expected to care for a patient with EVD. The program occurred in a simulation center with multiple flexible spaces and consisted of demonstration, multiple skills practice sessions, and a patient simulation case. We analyzed completed pre- and posttraining questionnaires. The questionnaire assessed their subjective level of confidence in three key areas: donning and doffing PPE, performing clinical skills while wearing PPE, and management of a contamination breach. RESULTS: This program was effectively deployed in the STRATUS Center for Medical Simulation over a 4-month period, with 220 health care professionals participating in the training and 195 participants completing the pre-/posttraining questionnaires. Our intervention significantly increased the confidence of participants on each primary objective (p = .001 for all three stations). DISCUSSION: This interprofessional simulation-based program has been shown to be a well-received method of training clinicians to manage patients collaboratively during an EVD outbreak. Our intent is that the skills taught in this training program would also be transferable to management of other infectious diseases in the clinical setting.",,"[""O'Keeffe, Dara Ann"", 'Bradley, Dorothy', 'Evans, Linda', 'Bustamante, Nirma', 'Timmel, Matthew', 'Akkineni, Roopa', 'Mulloy, Deborah', 'Goralnick, Eric', 'Pozner, Charles']",MedEdPORTAL.; 12:10433,,,True
f3a90e6992ef81870180a64caea939eccefee16c,PMC,"Molecular Characterization of Two Mitogen-Activated Protein Kinases: p38 MAP Kinase and Ribosomal S6 Kinase From Bombyx mori (Lepidoptera: Bombycidae), and Insight Into Their Roles in Response to BmNPV Infection",http://dx.doi.org/10.1093/jisesa/iey134,PMC6359879,30715437,CC BY-NC,"Proteins p38 map kinase and ribosomal S6 kinase (S6K) as members of mitogen-activated protein kinases (MAPKs) play important roles against pathogens. In this study, Bmp38 and BmS6K were identified as differentially expressed proteins from iTRAQ database. Bmp38 and BmS6K were expressed, and recombinant proteins were purified. The bioinformatics analysis showed that both proteins have serine/threonine-protein kinases, catalytic domain (S_TKc) with 360 and 753 amino acids, respectively. The real-time quantitative polymerase chain reaction (RT-qPCR) results suggest that Bmp38 and BmS6K had high expression in the midgut and hemolymph. The comparative expression level of Bmp38 and BmS6K in BC9 was upregulated than in P50 in the midgut after Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Western bolt results showed a positive correlation between RT-qPCR and iTRAQ data for Bmp38, but BmS6K data showed partial correlation with iTRAQ. Injection of anti-Bmp38 and anti-BmS6K serum suggested that Bmp38 may be involved against BmNPV infection, whereas BmS6K may require phosphorylation modification to inhibit BmNPV infection. Taken together, our results suggest that Bmp38 and BmS6k might play an important role in innate immunity of silkworm against BmNPV.",2019 Feb 2,"['Muhammad, Azharuddin', 'Toufeeq, Shahzad', 'Yu, Hai-Zhong', 'Wang, Jie', 'Zhang, Shang-Zhi', 'Li, Bing', 'Li, Zhen', 'Yang, Li-Ang', 'Hu, Pei', 'Ma, Yan', 'Xu, Jia-Ping']",J Insect Sci,,,True
f774e52f2267ee839ba5b026e12dfef588e15bfa,PMC,Overexpression of Tripartite Motif Conaining 55 (TRIM55) Inhibits Migration and Invasion of Hepatocellular Carcinoma (HCC) Cells via Epithelial-Mesenchymal Transition and Matrix Metalloproteinase-2 (MMP2),http://dx.doi.org/10.12659/MSM.910984,PMC6360872,30685767,CC BY-NC-ND,"BACKGROUND: Tripartite motif containing 55 (TRIM55) plays a regulatory role in assembly of sarcomeres, but few studies have assessed its function in hepatocellular carcinoma (HCC). MATREIAL/METHODS: Immunohistochemistry (IHC) was used to detect expression of TRIM55 in tissues samples of HCC patients. Transwell assay was used to study migration and invasion ability of HCC cells. Western blot and immunofluorescence (IF) were used to analyze mechanism of TRIM55 in cell migration and invasion. RESULTS: We found TRIM55 was downregulated in HCC tissues and was associated with prognosis of HCC patients. Cox regression analysis showed that TRIM55 was an independent risk factor of prognosis of HCC patients. Overexpression of TRIM55 was associated with lower cell migration and invasion ability, and it led to high expression of E-cadherin and low expression of Vimentin and MMP2. CONCLUSIONS: Our study found TRIM55 is an independent factor affecting the prognosis of HCC patients, and overexpression of TRIM55 inhibits migration and invasion of HCC cells through epithelial-mesenchymal transition and MMP2.",2019 Jan 27,"['Li, Xinyu', 'Huang, Lei', 'Gao, Weijie']",Med Sci Monit,,,True
319004f23d1af4357edb2a3862f2619be23a21a6,PMC,An updated roadmap for MERS-CoV research and product development: focus on diagnostics,http://dx.doi.org/10.1136/bmjgh-2018-001105,PMC6361340,30815285,CC BY-NC,"Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. In this review we identified sources for molecular and serological diagnostic tests used in MERS-CoV detection, case management and outbreak investigations, as well as surveillance for humans and animals (camels), and summarised the performance of currently available tests, diagnostic needs, and associated challenges for diagnostic test development and implementation. A more detailed understanding of the kinetics of infection of MERS-CoV is needed in order to optimise the use of existing assays. Notably, MERS-CoV point-of-care tests are needed in order to optimise supportive care and to minimise transmission risk. However, for new test development, sourcing clinical material continues to be a major challenge to achieving assay validation. Harmonisation and standardisation of laboratory methods are essential for surveillance and for a rapid and effective international response to emerging diseases. Routine external quality assessment, along with well-characterised and up-to-date proficiency panels, would provide insight into MERS-CoV diagnostic performance worldwide. A defined set of Target Product Profiles for diagnostic technologies will be developed by WHO to address these gaps in MERS-CoV outbreak management.",2019 Feb 1,"['Kelly-Cirino, Cassandra', 'Mazzola, Laura T', 'Chua, Arlene', 'Oxenford, Christopher J', 'Van Kerkhove, Maria D']",BMJ Glob Health,,,True
dd703cbcefa01f6fb1441333a897c57d90f011f9,PMC,An updated roadmap for MERS-CoV research and product development: focus on diagnostics,http://dx.doi.org/10.1136/bmjgh-2018-001105,PMC6361340,30815285,CC BY-NC,"Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. In this review we identified sources for molecular and serological diagnostic tests used in MERS-CoV detection, case management and outbreak investigations, as well as surveillance for humans and animals (camels), and summarised the performance of currently available tests, diagnostic needs, and associated challenges for diagnostic test development and implementation. A more detailed understanding of the kinetics of infection of MERS-CoV is needed in order to optimise the use of existing assays. Notably, MERS-CoV point-of-care tests are needed in order to optimise supportive care and to minimise transmission risk. However, for new test development, sourcing clinical material continues to be a major challenge to achieving assay validation. Harmonisation and standardisation of laboratory methods are essential for surveillance and for a rapid and effective international response to emerging diseases. Routine external quality assessment, along with well-characterised and up-to-date proficiency panels, would provide insight into MERS-CoV diagnostic performance worldwide. A defined set of Target Product Profiles for diagnostic technologies will be developed by WHO to address these gaps in MERS-CoV outbreak management.",2019 Feb 1,"['Kelly-Cirino, Cassandra', 'Mazzola, Laura T', 'Chua, Arlene', 'Oxenford, Christopher J', 'Van Kerkhove, Maria D']",BMJ Glob Health,,,False
e74f5e16ea50735c376959c210d2a06023c1245c,PMC,An updated roadmap for MERS-CoV research and product development: focus on diagnostics,http://dx.doi.org/10.1136/bmjgh-2018-001105,PMC6361340,30815285,CC BY-NC,"Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. In this review we identified sources for molecular and serological diagnostic tests used in MERS-CoV detection, case management and outbreak investigations, as well as surveillance for humans and animals (camels), and summarised the performance of currently available tests, diagnostic needs, and associated challenges for diagnostic test development and implementation. A more detailed understanding of the kinetics of infection of MERS-CoV is needed in order to optimise the use of existing assays. Notably, MERS-CoV point-of-care tests are needed in order to optimise supportive care and to minimise transmission risk. However, for new test development, sourcing clinical material continues to be a major challenge to achieving assay validation. Harmonisation and standardisation of laboratory methods are essential for surveillance and for a rapid and effective international response to emerging diseases. Routine external quality assessment, along with well-characterised and up-to-date proficiency panels, would provide insight into MERS-CoV diagnostic performance worldwide. A defined set of Target Product Profiles for diagnostic technologies will be developed by WHO to address these gaps in MERS-CoV outbreak management.",2019 Feb 1,"['Kelly-Cirino, Cassandra', 'Mazzola, Laura T', 'Chua, Arlene', 'Oxenford, Christopher J', 'Van Kerkhove, Maria D']",BMJ Glob Health,,,False
b8ac98738fd685d41d8750e577231b3c021f0dd1,PMC,An updated roadmap for MERS-CoV research and product development: focus on diagnostics,http://dx.doi.org/10.1136/bmjgh-2018-001105,PMC6361340,30815285,CC BY-NC,"Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. In this review we identified sources for molecular and serological diagnostic tests used in MERS-CoV detection, case management and outbreak investigations, as well as surveillance for humans and animals (camels), and summarised the performance of currently available tests, diagnostic needs, and associated challenges for diagnostic test development and implementation. A more detailed understanding of the kinetics of infection of MERS-CoV is needed in order to optimise the use of existing assays. Notably, MERS-CoV point-of-care tests are needed in order to optimise supportive care and to minimise transmission risk. However, for new test development, sourcing clinical material continues to be a major challenge to achieving assay validation. Harmonisation and standardisation of laboratory methods are essential for surveillance and for a rapid and effective international response to emerging diseases. Routine external quality assessment, along with well-characterised and up-to-date proficiency panels, would provide insight into MERS-CoV diagnostic performance worldwide. A defined set of Target Product Profiles for diagnostic technologies will be developed by WHO to address these gaps in MERS-CoV outbreak management.",2019 Feb 1,"['Kelly-Cirino, Cassandra', 'Mazzola, Laura T', 'Chua, Arlene', 'Oxenford, Christopher J', 'Van Kerkhove, Maria D']",BMJ Glob Health,,,False
9e9667fc7fcb441ee60a45d5cc2a8550205c9ad3,PMC,Importance of diagnostics in epidemic and pandemic preparedness,http://dx.doi.org/10.1136/bmjgh-2018-001179,PMC6362765,30815287,CC BY-NC,"Diagnostics are fundamental for successful outbreak containment. In this supplement, ‘Diagnostic preparedness for WHO Blueprint pathogens’, we describe specific diagnostic challenges presented by selected priority pathogens most likely to cause future epidemics. Some challenges to diagnostic preparedness are common to all outbreak situations, as highlighted by recent outbreaks of Ebola, Zika and yellow fever. In this article, we review these overarching challenges and explore potential solutions. Challenges include fragmented and unreliable funding pathways, limited access to specimens and reagents, inadequate diagnostic testing capacity at both national and community levels of healthcare and lack of incentives for companies to develop and manufacture diagnostics for priority pathogens during non-outbreak periods. Addressing these challenges in an efficient and effective way will require multiple stakeholders—public and private—coordinated in implementing a holistic approach to diagnostics preparedness. All require strengthening of healthcare system diagnostic capacity (including surveillance and education of healthcare workers), establishment of sustainable financing and market strategies and integration of diagnostics with existing mechanisms. Identifying overlaps in diagnostic development needs across different priority pathogens would allow more timely and cost-effective use of resources than a pathogen by pathogen approach; target product profiles for diagnostics should be refined accordingly. We recommend the establishment of a global forum to bring together representatives from all key stakeholders required for the response to develop a coordinated implementation plan. In addition, we should explore if and how existing mechanisms to address challenges to the vaccines sector, such as Coalition for Epidemic Preparedness Innovations and Gavi, could be expanded to cover diagnostics.",2019 Jan 29,"['Kelly-Cirino, Cassandra D', 'Nkengasong, John', 'Kettler, Hannah', 'Tongio, Isabelle', 'Gay-Andrieu, Françoise', 'Escadafal, Camille', 'Piot, Peter', 'Peeling, Rosanna W', 'Gadde, Renuka', 'Boehme, Catharina']",BMJ Glob Health,,,True
fc1f4b62e7c63ec2a3536401ce6aea880dca8512,PMC,IgY antibodies for the immunoprophylaxis and therapy of respiratory infections,http://dx.doi.org/10.1080/21645515.2018.1514224,PMC6363154,30230944,CC BY-NC-ND,"Emergence of drug resistance among the causative organisms for respiratory tract infections represents a critical challenge to the global health care community. Further, although vaccination can prevent disease, vaccine development is impeded by several factors. Therefore, novel approaches to treat and manage respiratory infections are urgently needed. Passive immunization represents a possible alternative to meet this need. Immunoglobulin Y antibodies (IgYs) from the yolk of chicken eggs have previously been used against bacterial and viral infections in human and animals. Their advantages include lack of reaction with mammalian Fc receptors, low production cost, and ease of extraction. Compared to mammalian IgGs, they have higher target specificity and greater binding avidity. They also possess remarkable pathogen-neutralizing activity in the respiratory tract and lungs. In this review, we provide an overview of avian IgYs and describe their potential therapeutic applications for the prevention and treatment of respiratory infections.",2018 Sep 19,"['Abbas, Aymn Talat', 'El-Kafrawy, Sherif Aly', 'Sohrab, Sayed Sartaj', 'Azhar, Esam Ibraheem Ahmed']",Hum Vaccin Immunother,,,True
7f69a764a32e9fefc971d79582da33db151cdeb5,PMC,BAR scaffolds drive membrane fission by crowding disordered domains,http://dx.doi.org/10.1083/jcb.201807119,PMC6363457,30504247,CC BY-NC-SA,"Cellular membranes are continuously remodeled. The crescent-shaped bin-amphiphysin-rvs (BAR) domains remodel membranes in multiple cellular pathways. Based on studies of isolated BAR domains in vitro, the current paradigm is that BAR domain–containing proteins polymerize into cylindrical scaffolds that stabilize lipid tubules. But in nature, proteins that contain BAR domains often also contain large intrinsically disordered regions. Using in vitro and live cell assays, here we show that full-length BAR domain–containing proteins, rather than stabilizing membrane tubules, are instead surprisingly potent drivers of membrane fission. Specifically, when BAR scaffolds assemble at membrane surfaces, their bulky disordered domains become crowded, generating steric pressure that destabilizes lipid tubules. More broadly, we observe this behavior with BAR domains that have a range of curvatures. These data suggest that the ability to concentrate disordered domains is a key driver of membrane remodeling and fission by BAR domain–containing proteins.",2019 Feb 4,"['Snead, Wilton T.', 'Zeno, Wade F.', 'Kago, Grace', 'Perkins, Ryan W.', 'Richter, J Blair', 'Zhao, Chi', 'Lafer, Eileen M.', 'Stachowiak, Jeanne C.']",J Cell Biol,,,True
d84514633b2de3a00d06955978cb5a2eebe0ea7d,PMC,BAR scaffolds drive membrane fission by crowding disordered domains,http://dx.doi.org/10.1083/jcb.201807119,PMC6363457,30504247,CC BY-NC-SA,"Cellular membranes are continuously remodeled. The crescent-shaped bin-amphiphysin-rvs (BAR) domains remodel membranes in multiple cellular pathways. Based on studies of isolated BAR domains in vitro, the current paradigm is that BAR domain–containing proteins polymerize into cylindrical scaffolds that stabilize lipid tubules. But in nature, proteins that contain BAR domains often also contain large intrinsically disordered regions. Using in vitro and live cell assays, here we show that full-length BAR domain–containing proteins, rather than stabilizing membrane tubules, are instead surprisingly potent drivers of membrane fission. Specifically, when BAR scaffolds assemble at membrane surfaces, their bulky disordered domains become crowded, generating steric pressure that destabilizes lipid tubules. More broadly, we observe this behavior with BAR domains that have a range of curvatures. These data suggest that the ability to concentrate disordered domains is a key driver of membrane remodeling and fission by BAR domain–containing proteins.",2019 Feb 4,"['Snead, Wilton T.', 'Zeno, Wade F.', 'Kago, Grace', 'Perkins, Ryan W.', 'Richter, J Blair', 'Zhao, Chi', 'Lafer, Eileen M.', 'Stachowiak, Jeanne C.']",J Cell Biol,,,True
6a14ff1798aa6ca90d45bab127740593ab37fac3,PMC,Changes in Chemokines and Chemokine Receptors Expression in a Mouse Model of Alzheimer's Disease,http://dx.doi.org/10.7150/ijbs.26703,PMC6367555,30745834,CC BY-NC,"The amyloid precursor protein plus presenilin-1 (APP/PS1) mice are a frequently-used model for Alzheimer's disease studies (AD). However, the data relevant to which proteins are involved in inflammatory mechanism are not sufficiently well-studied using the AD mouse model. Using behavioral studies, quantitative RT-PCR and Western-blot techniques, significant findings were determined by the expression of proteins involved in inflammation comparing APP/PS1 and Wild type mice. Increased GFAP expression could be associated with the elevation in number of reactive astrocytes. IL-3 is involved in inflammation and ABDF1 intervenes normally in the transport across cell membranes and both were found up-regulated in APP/PS1 mice compared to Wild type mice. Furthermore, CCR5 expression was decreased and both CCL3 and CCL4 chemokines were highly expressed indicating a possible gliosis and probably an increase in chemotaxis from lymphocytes and T cell generation. We also noted for the first time, a CCR8 increase expression with diminution of its CCL1 chemokine, both normally involved in protection from bacterial infection and demyelination. Control of inflammatory proteins will be the next step in understanding the progression of AD and also in determining the mechanisms that can develop in this disease.",2019 Jan 1,"['Jorda, Adrián', 'Cauli, Omar', 'Santonja, Jose M.', 'Aldasoro, Martin', 'Aldasoro, Constanza', 'Obrador, Elena', 'Vila, Jose Ma', 'Mauricio, Ma Dolores', 'Iradi, Antonio', 'Guerra-Ojeda, Sol', 'Marchio, Patricia', 'Valles, Soraya L.']",Int J Biol Sci,,,True
1999185dad27d52562c1dfe77bb72f06bdaf5084,PMC,Expression and serological application of recombinant epitope-repeat protein carrying an immunodominant epitope of Newcastle disease virus nucleoprotein,http://dx.doi.org/10.7774/cevr.2019.8.1.27,PMC6369128,30775348,CC BY-NC,PURPOSE: The aim of the present study was to develop a serodiagnostic test for differentiation infected from vaccinated animal (DIVA) strategy accompanying the marker vaccine lacking an immunodominant epitope (IDE) of nucleoprotein of Newcastle disease virus (NDV). MATERIALS AND METHODS: Recombinant epitope-repeat protein (rERP) gene encoding eight repeats of the IDE sequence (ETQFLDLMRAVANSMR) by tetra-glycine linker was synthesized. Recombinant baculovirus carrying the rERP gene was generated to express the rERP in insect cells. Specificity and sensitivity of an indirect enzyme-linked immunosorbent assay (ELISA) employing the rERP was evaluated. RESULTS: The rERP with molecular weight of 20 kDa was successfully expressed by the recombinant baculovirus in an insect-baculovirus system. The rERP was antigenically functional as demonstrated by Western blotting. An indirect ELISA employing the rERP was developed and its specificity and sensitivity was determined. The ELISA test allowed discrimination of NDV infected sera from epitope deletion virus vaccinated sera. CONCLUSION: The preliminary results represent rERP ELISA as a promising DIVA diagnostic tool.,2019 Jan 31,"['Gaikwad, Satish S.', 'Lee, Hyun-Jeong', 'Kim, Ji-Ye', 'Choi, Kang-Seuk']",Clin Exp Vaccine Res,,,True
de4399a1034294c5aecf4f318fd99ca559a762ea,PMC,Absence of neutralizing activity in serum 1 year after successful treatment with antivirals and recovery from MERS in South Korea,http://dx.doi.org/10.7774/cevr.2019.8.1.86,PMC6369131,30775355,CC BY-NC,"We evaluated the neutralizing activity in serum from three patients >1 year after recovery from Middle East respiratory syndrome (MERS) associated with mild pneumonia treated with antivirals during the MERS outbreak in South Korea at 2015. The neutralizing activity in serum was measured by pseudovirus inhibition assays. Three-fold diluted serum of subjects showed only 9.7%, 10.3%, and 2.2% reductions in relative light units. So, significant neutralizing activity was not demonstrated in any sera of three patients with mild pneumonia >1 year after being successfully treated with antiviral agents and recovering from MERS coronavirus infection.",2019 Jan 31,"['Choi, Jun Yong', 'Oh, Jin Ok', 'Ahn, Jin Young', 'Choi, Heun', 'Kim, Jung Ho', 'Seong, Hye', 'Jeong, Su Jin', 'Ku, Nam Su', 'Yeom, Joon-Sup', 'Choi, Jae-Phil']",Clin Exp Vaccine Res,,,True
1052ac76b8c769749a3400eb9479e34a35407eae,PMC,Small molecule ISRIB suppresses the integrated stress response within a defined window of activation,http://dx.doi.org/10.1073/pnas.1815767116,PMC6369741,30674674,CC BY-NC-ND,"Activation of the integrated stress response (ISR) by a variety of stresses triggers phosphorylation of the α-subunit of translation initiation factor eIF2. P-eIF2α inhibits eIF2B, the guanine nucleotide exchange factor that recycles inactive eIF2•GDP to active eIF2•GTP. eIF2 phosphorylation thereby represses translation. Persistent activation of the ISR has been linked to the development of several neurological disorders, and modulation of the ISR promises new therapeutic strategies. Recently, a small-molecule ISR inhibitor (ISRIB) was identified that rescues translation in the presence of P-eIF2α by facilitating the assembly of more active eIF2B. ISRIB enhances cognitive memory processes and has therapeutic effects in brain-injured mice without displaying overt side effects. While using ISRIB to investigate the ISR in picornavirus-infected cells, we observed that ISRIB rescued translation early in infection when P-eIF2α levels were low, but not late in infection when P-eIF2α levels were high. By treating cells with varying concentrations of poly(I:C) or arsenite to induce the ISR, we provide additional proof that ISRIB is unable to inhibit the ISR when intracellular P-eIF2α concentrations exceed a critical threshold level. Together, our data demonstrate that the effects of pharmacological activation of eIF2B are tuned by P-eIF2α concentration. Thus, ISRIB can mitigate undesirable outcomes of low-level ISR activation that may manifest neurological disease but leaves the cytoprotective effects of acute ISR activation intact. The insensitivity of cells to ISRIB during acute ISR may explain why ISRIB does not cause overt toxic side effects in vivo.",2019 Feb 5,"['Rabouw, Huib H.', 'Langereis, Martijn A.', 'Anand, Aditya A.', 'Visser, Linda J.', 'de Groot, Raoul J.', 'Walter, Peter', 'van Kuppeveld, Frank J. M.']",Proc Natl Acad Sci U S A,,,True
6fe5c74868af62cfacb629af957915de0b094af9,PMC,Small molecule ISRIB suppresses the integrated stress response within a defined window of activation,http://dx.doi.org/10.1073/pnas.1815767116,PMC6369741,30674674,CC BY-NC-ND,"Activation of the integrated stress response (ISR) by a variety of stresses triggers phosphorylation of the α-subunit of translation initiation factor eIF2. P-eIF2α inhibits eIF2B, the guanine nucleotide exchange factor that recycles inactive eIF2•GDP to active eIF2•GTP. eIF2 phosphorylation thereby represses translation. Persistent activation of the ISR has been linked to the development of several neurological disorders, and modulation of the ISR promises new therapeutic strategies. Recently, a small-molecule ISR inhibitor (ISRIB) was identified that rescues translation in the presence of P-eIF2α by facilitating the assembly of more active eIF2B. ISRIB enhances cognitive memory processes and has therapeutic effects in brain-injured mice without displaying overt side effects. While using ISRIB to investigate the ISR in picornavirus-infected cells, we observed that ISRIB rescued translation early in infection when P-eIF2α levels were low, but not late in infection when P-eIF2α levels were high. By treating cells with varying concentrations of poly(I:C) or arsenite to induce the ISR, we provide additional proof that ISRIB is unable to inhibit the ISR when intracellular P-eIF2α concentrations exceed a critical threshold level. Together, our data demonstrate that the effects of pharmacological activation of eIF2B are tuned by P-eIF2α concentration. Thus, ISRIB can mitigate undesirable outcomes of low-level ISR activation that may manifest neurological disease but leaves the cytoprotective effects of acute ISR activation intact. The insensitivity of cells to ISRIB during acute ISR may explain why ISRIB does not cause overt toxic side effects in vivo.",2019 Feb 5,"['Rabouw, Huib H.', 'Langereis, Martijn A.', 'Anand, Aditya A.', 'Visser, Linda J.', 'de Groot, Raoul J.', 'Walter, Peter', 'van Kuppeveld, Frank J. M.']",Proc Natl Acad Sci U S A,,,True
01297dffaf94c1314ca46088f7b829b8383c2f73,PMC,Glycosylation of the HIV-1 Env V1V2 loop to form a native-like structure may not be essential with a nanoparticle vaccine,http://dx.doi.org/10.2217/fvl-2018-0174,PMC6378949,30815025,CC BY-NC-ND,,2019 Feb 10,"['Karch, Christopher P', 'Matyas, Gary R', 'Burkhard, Peter', 'Beck, Zoltan']",Future Virol,,,True
6f64870ea0f8f51525b16926dc6dbb42911f850f,PMC,Suspected phenobarbital-induced fever in a cat,http://dx.doi.org/10.1177/2055116919830214,PMC6379798,30800413,CC BY-NC,"CASE SUMMARY: A 3-year-old spayed female domestic shorthair cat developed a fever 1 week after starting the anticonvulsant phenobarbital. A diagnostic work-up for seizures and subsequent onset of fever of unknown origin, consisting of MRI of the brain, cerebrospinal fluid analysis and infectious disease testing, was unremarkable. The cat was switched from phenobarbital onto pregabalin with complete resolution of the fever within 24 h, consistent with a drug-induced fever following phenobarbital administration. RELEVANCE AND NOVEL INFORMATION: While anticonvulsant hypersensitivities have been reported and studied in veterinary medicine, phenobarbital-induced fever outside of the context of systemic clinical signs has not been documented in the veterinary scientific literature. Drug-induced fever secondary to anticonvulsants should be considered in patients that develop a fever after starting anticonvulsant therapy with an unrewarding diagnostic work-up for fever of unknown origin.",2019 Feb 18,"['Djani, Dylan M', 'Draper, William E']",JFMS Open Rep,,,True
47bd7df352db2b1b093566b04fc328d6f0292c1b,PMC,Comparison of fit factors among healthcare providers working in the Emergency Department Center before and after training with three types of N95 and higher filter respirators,http://dx.doi.org/10.1097/MD.0000000000014250,PMC6380834,30732139,CC BY-NC,"INTRODUCTION: N95 or higher filtering respirators have been recommended in healthcare settings, although there is still a risk of infection due to the improper selection and wearing of respirators. We aimed to assess the effects of training with N95 or higher filter respirators on the protection performance of respirators among healthcare providers in the emergency medical center (EMC). METHODS: This randomized crossover study evaluated 23 healthcare providers. Quantitative fit tests (QNFTs) were performed before and after training using three types of N95 or higher filter respirators (cup-type, fold-type, valve-type). Training was performed by lecture, real-time feedback, and fit check. The primary outcome was the fit factor, and the secondary outcomes were overall fit factor, adequate protection rate, and respiratory preference. RESULTS: Fit factors, overall fit factor, and adequate protection rate were higher after training than before training for the 3 types of respirators (all P < .05). For normal breathing, fit factors before and after training were 121 (10–185) vs 192 (161–200) for cup-type, 200 (39–200) vs 200 (200–200) for fold-type, and 85 (18–157) vs 173 (117–200) for valve-type. For normal breathing, the adequate protection rates before and after training were 62 (0–100) vs 100 (90–100) for cup-type, 100 (0–100) vs 100 (100–100) for fold-type, and 19 (0–100) vs 100 (44–100) for valve-type (all P < .05). The most preferred respirator type was the valve-type (10 persons, 45.5%). CONCLUSIONS: Training on wearing an N95 or higher respirator improved the protection performance of respirators among healthcare providers working in the EMC. The selection of proper respirators and training would be beneficial to the safety of healthcare providers.",2019 Feb 8,"['Kim, Hongjung', 'Lee, Juncheol', 'Lee, Sanghyun', 'Oh, Jaehoon', 'Kang, Boseung', 'Lim, Tae Ho', 'Kang, Hyunggoo']",Medicine (Baltimore),,,True
93c68999496870d3c22d197c05645a9bd747c8cc,PMC,Comparison of fit factors among healthcare providers working in the Emergency Department Center before and after training with three types of N95 and higher filter respirators,http://dx.doi.org/10.1097/MD.0000000000014250,PMC6380834,30732139,CC BY-NC,"INTRODUCTION: N95 or higher filtering respirators have been recommended in healthcare settings, although there is still a risk of infection due to the improper selection and wearing of respirators. We aimed to assess the effects of training with N95 or higher filter respirators on the protection performance of respirators among healthcare providers in the emergency medical center (EMC). METHODS: This randomized crossover study evaluated 23 healthcare providers. Quantitative fit tests (QNFTs) were performed before and after training using three types of N95 or higher filter respirators (cup-type, fold-type, valve-type). Training was performed by lecture, real-time feedback, and fit check. The primary outcome was the fit factor, and the secondary outcomes were overall fit factor, adequate protection rate, and respiratory preference. RESULTS: Fit factors, overall fit factor, and adequate protection rate were higher after training than before training for the 3 types of respirators (all P < .05). For normal breathing, fit factors before and after training were 121 (10–185) vs 192 (161–200) for cup-type, 200 (39–200) vs 200 (200–200) for fold-type, and 85 (18–157) vs 173 (117–200) for valve-type. For normal breathing, the adequate protection rates before and after training were 62 (0–100) vs 100 (90–100) for cup-type, 100 (0–100) vs 100 (100–100) for fold-type, and 19 (0–100) vs 100 (44–100) for valve-type (all P < .05). The most preferred respirator type was the valve-type (10 persons, 45.5%). CONCLUSIONS: Training on wearing an N95 or higher respirator improved the protection performance of respirators among healthcare providers working in the EMC. The selection of proper respirators and training would be beneficial to the safety of healthcare providers.",2019 Feb 8,"['Kim, Hongjung', 'Lee, Juncheol', 'Lee, Sanghyun', 'Oh, Jaehoon', 'Kang, Boseung', 'Lim, Tae Ho', 'Kang, Hyunggoo']",Medicine (Baltimore),,,True
ab9abbe85c17fc97b9b10fefa729dae44c12c65d,PMC,Modeling the impact of quarantine during an outbreak of Ebola virus disease,http://dx.doi.org/10.1016/j.idm.2019.01.003,PMC6382747,30828672,CC BY-NC-ND,"The quarantine of people suspected of being exposed to an infectious agent is one of the most basic public health measure that has historically been used to combat the spread of communicable diseases in human communities. This study presents a new deterministic model for assessing the population-level impact of the quarantine of individuals suspected of being exposed to disease on the spread of the 2014–2015 outbreaks of Ebola viral disease. It is assumed that quarantine is imperfect (i.e., individuals can acquire infection during quarantine). In the absence of quarantine, the model is shown to exhibit global dynamics with respect to the disease-free and its unique endemic equilibrium when a certain epidemiological threshold (denoted by [Formula: see text]) is either less than or greater than unity. Thus, unlike the full model with imperfect quarantine (which is known to exhibit the phenomenon of backward bifurcation), the version of the model with no quarantine does not undergo a backward bifurcation. Using data relevant to the 2014–2015 Ebola transmission dynamics in the three West African countries (Guinea, Liberia and Sierra Leone), uncertainty analysis of the model show that, although the current level and effectiveness of quarantine can lead to significant reduction in disease burden, they fail to bring the associated quarantine reproduction number ([Formula: see text]) to a value less than unity (which is needed to make effective disease control or elimination feasible). This reduction of [Formula: see text] is, however, very possible with a modest increase in quarantine rate and effectiveness. It is further shown, via sensitivity analysis, that the parameters related to the effectiveness of quarantine (namely the parameter associated with the reduction in infectiousness of infected quarantined individuals and the contact rate during quarantine) are the main drivers of the disease transmission dynamics. Overall, this study shows that the singular implementation of a quarantine intervention strategy can lead to the effective control or elimination of Ebola viral disease in a community if its coverage and effectiveness levels are high enough.",2019 Feb 5,"['Dénes, Attila', 'Gumel, Abba B.']",Infect Dis Model,,,False
0adc2dfd5f26656ce3527dbb5dec379d44d0601e,PMC,Infectious Complications After Umbilical Cord Blood Transplantation for Hematological Malignancy,http://dx.doi.org/10.1093/ofid/ofz037,PMC6386816,30815505,CC BY-NC-ND,"BACKGROUND: Umbilical cord blood transplant (UCBT) is used for patients who do not have a matched donor, but engraftment often takes longer than with a standard allogeneic transplant, likely increasing the risk for infection. We characterized specific infections and outcomes in adults undergoing UCBT at our 2 centers. METHODS: All adults who underwent UCBT between January 1, 2006 and December 31, 2015 were included. Infectious episodes from 6 months before to 2 years after UCBT were reviewed. RESULTS: Fifty-seven patients underwent UCBT; 47 had neutrophil engraftment. A total of 179 infectious episodes occurred in 55 patients, 73 (41%) within 30 days post-UCBT. Viruses caused 85 (47%) infections. Cytomegalovirus caused 32 infectious episodes and was most common from day 30 to 100. Human herpesvirus 6 occurred in 28 episodes, was most common within 30 days, and caused 1 death. Bacteria were responsible for 82 (46%) infections, most commonly bacteremias due to Staphylococcus spp, Enterococcus spp, and Enterobacteriaceae. Of 11 invasive fungal infections, 9 were aspergillosis, 4 of which were fatal. Overall mortality was 56% in the first year. Thirteen deaths were from infection; 11 occurred in the first 100 days and 7 in the first 30 days post-UCBT. Of 10 patients who never engrafted, 9 died, 6 from infection, within 100 days post-UCBT. CONCLUSIONS: Infectious complications were common after UCBT, especially in the first 30 days. Deaths from viral infections were fewer than expected. Delayed engraftment and nonengraftment continue to convey increased risk for fatal bacterial and fungal infections post-UCBT.",2019 Feb 22,"['Linder, Kathleen A', 'McDonald, Philip J', 'Kauffman, Carol A', 'Revankar, Sanjay G', 'Chandrasekar, Pranatharthi H', 'Miceli, Marisa H']",Open Forum Infect Dis,,,True
62d641575bf71e839a2c4f4c7a6dc398ef2b5a0a,PMC,The development and application of Laboratory Animal Science in China,http://dx.doi.org/10.1002/ame2.12047,PMC6388048,30891573,CC BY-NC,,2018 Dec 21,"['Vergara, Patri', 'Morahan, Grant']",Animal Model Exp Med,,,True
5fbe76b0ae7ef869d483dfa3844a8d4f66f65c8f,PMC,The battle against SARS and MERS coronaviruses: Reservoirs and Animal Models,http://dx.doi.org/10.1002/ame2.12017,PMC6388065,30891557,CC BY-NC,"In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus (SARS‐CoV) and the emerging Middle East respiratory syndrome coronavirus (MERS‐CoV), induces acute respiratory failure, resulting in high mortality. Irregular coronavirus related epidemics indicate that the evolutionary origins of these two pathogens need to be identified urgently and there are still questions related to suitable laboratory animal models. Thus, in this review we aim to highlight key discoveries concerning the animal origin of the virus and summarize and compare current animal models.",2018 Jul 28,"['Gong, Shu‐ran', 'Bao, Lin‐lin']",Animal Model Exp Med,,,True
4707f1bde6c93904ce5481e8d38e86a3fc2cd36e,PMC,Transient plant production of Salmonella Typhimurium diagnostic antibodies,http://dx.doi.org/10.1016/j.btre.2019.e00314,PMC6389800,30847285,CC BY-NC-ND,"Salmonella Typhimurium is one of the most important zoonotic pathogens worldwide and a major cause of economic losses in the pig production chain. The emergence of multi-drug resistant strains over the past years has led to considerations about an enhanced surveillance of bacterial food contamination. Currently, ELISA is the method of choice for high throughput identification of S. Typhimurium. The sensitivity and specificity of this assay might be improved by application of new diagnostic antibodies. We focused on plant-based expression of candidate diagnostic TM43-E10 antibodies discovered using as antigen the S. Typhimurium OmpD protein. The scFv-TM43-E10 and scFv-Fc-TM43-E10 antibody derivatives have been successfully produced in N. benthamiana using a deconstructed movement-deficient PVX vector supplemented with the γb silencing suppressor from Poa semilatent virus. The plant-made antibodies showed the same antigen-binding specificity as that of the microbial/mammalian cell-produced counterparts and could recognize the OmpD antigen in S. Typhimurium infected plant samples.",2019 Feb 12,"['Kopertekh, Lilya', 'Meyer, Torsten', 'Freyer, Cornelia', 'Hust, Michael']",Biotechnol Rep (Amst),,,False
0dc475f4419836c2dc352073498f56ae982170a0,PMC,"Age-related prevalence of common upper respiratory pathogens, based on the application of the FilmArray Respiratory panel in a tertiary hospital in Greece",http://dx.doi.org/10.1097/MD.0000000000010903,PMC6392546,29851817,CC BY-NC,"The FilmArray Respiratory Panel (FA-RP) is an FDA certified multiplex PCR that can detect 17 viruses and 3 bacteria responsible for upper respiratory tract infections, thus it is potentially useful to the assessment of the age-related prevalence of these pathogens. In this observational study, we retrospectively analyzed the results of all the respiratory samples, which had been processed during 1 year-period (November 2015 to November 2016) with the FA-RP, in the Central Laboratories of Hygeia & Mitera General Hospitals of Athens, Greece. In order to have an age-related distribution, the following age groups were implemented: (<2), (≥2, <5), (≥5, <10), (≥10, <18), (≥18, <45), (≥45, <65), and (≥65) years old. Among 656 respiratory samples tested, 362 (55%) were from male and 294 (45%) from female patients, while 356 (54.3%) were positive and 300 (45.7%) negative. In the first age-group (<2), 41/121 samples (33.9%) revealed human rhinovirus/enterovirus (HRV) and 16 (13.2%) adenovirus (Adv), followed by respiratory syncytial virus (RSV), coronavirus, human metapneumovirus (Hmpv), and parainfluenza viruses (PIV). In the age-group (≥2, <5), Adv predominated with 37/147 samples (25.2%), followed by HRV, RSV, coronavirus (all types), and influenza, Hmpv and PIV. In the age-group (≥5, <10), HRV was identified in 25/80 samples (31.3%), Adv in 18 (22.5%), influenza in 11 (13.8%), and Hmpv in 6 (7.5%). Influenza predominated in the age-group (≥10, <18), with 4/22 samples (18.2%), while in the remaining age-groups (≥18), HRV was the commonest isolated pathogen, 33/286 (11.5%), followed by influenza with 20 (7%) (influenza A H1-2009, 11/20). In our patient series, HRV seemed to prevail in most age-groups, followed by Adv, although Influenza was the second most frequent pathogen isolated in the age-groups (≥18). Moreover, increasing age corresponded to increasing possibility of having a negative sample, indicating that FilmArray may be more useful before adolescence.",2018 Jun 1,"['Tsagarakis, Nikolaos J.', 'Sideri, Anthi', 'Makridis, Panagiotis', 'Triantafyllou, Argyro', 'Stamoulakatou, Alexandra', 'Papadogeorgaki, Eleni']",Medicine (Baltimore),,,True
5eb49e806422f7b236b088d46352af5874b52700,PMC,Schmallenberg virus induces apoptosis in Vero cell line via extrinsic and intrinsic pathways in a time and dose dependent manner,http://dx.doi.org/10.1292/jvms.18-0582,PMC6395206,30541984,CC BY-NC-ND,"Schmallenberg virus (SBV), discovered in 2011 in Germany, is associated with clinical manifestations of fever, diarrhea, reduced milk yield, abortions and congenital malformations in ruminants. Despite many studies performed for SBV, there is no detailed research on in vitro apoptotic effect of SBV. This study is aimed to determine apoptosis pathways and role of pro-apoptotic and anti-apoptotic molecules in Vero cells infected with SBV. The study results showed that SBV induced apoptosis via both extrinsic and intrinsic pathways by activating both caspase-8 and caspase-9, respectively. Expression analyses of pro-apoptotic (Bax, Bak and Puma) and anti-apoptotic (Bcl-2 and Bcl-XL) genes revealed that SBV-induced apoptosis causes upregulation of pro-apoptotic genes, dominantly via Puma gene, whereas Bcl-2 and Bcl-XL genes were downregulated. In conclusion, this is the first detailed report about SBV induced apoptosis in the Vero cells via both extrinsic and intrinsic cascades and apoptosis induction is seem to be regulated by Puma.",2019 Feb 12,"['AKSOY, Emel', 'AZKUR, Ahmet Kursat']",J Vet Med Sci,,,True
ac49bb9b1f83ff26a1ffda195c8f06b9cdf72b3a,PMC,Schmallenberg virus induces apoptosis in Vero cell line via extrinsic and intrinsic pathways in a time and dose dependent manner,http://dx.doi.org/10.1292/jvms.18-0582,PMC6395206,30541984,CC BY-NC-ND,"Schmallenberg virus (SBV), discovered in 2011 in Germany, is associated with clinical manifestations of fever, diarrhea, reduced milk yield, abortions and congenital malformations in ruminants. Despite many studies performed for SBV, there is no detailed research on in vitro apoptotic effect of SBV. This study is aimed to determine apoptosis pathways and role of pro-apoptotic and anti-apoptotic molecules in Vero cells infected with SBV. The study results showed that SBV induced apoptosis via both extrinsic and intrinsic pathways by activating both caspase-8 and caspase-9, respectively. Expression analyses of pro-apoptotic (Bax, Bak and Puma) and anti-apoptotic (Bcl-2 and Bcl-XL) genes revealed that SBV-induced apoptosis causes upregulation of pro-apoptotic genes, dominantly via Puma gene, whereas Bcl-2 and Bcl-XL genes were downregulated. In conclusion, this is the first detailed report about SBV induced apoptosis in the Vero cells via both extrinsic and intrinsic cascades and apoptosis induction is seem to be regulated by Puma.",2019 Feb 12,"['AKSOY, Emel', 'AZKUR, Ahmet Kursat']",J Vet Med Sci,,,False
70fd2c4e38970a59c42925daef90f674d7b21302,PMC,What Have We Learned About Middle East Respiratory Syndrome Coronavirus Emergence in Humans? A Systematic Literature Review,http://dx.doi.org/10.1089/vbz.2017.2191,PMC6396572,30676269,CC BY-NC,"Background: Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in humans in 2012. A systematic literature review was conducted to synthesize current knowledge and identify critical knowledge gaps. Materials and Methods: We conducted a systematic review on MERS-CoV using PRISMA guidelines. We identified 407 relevant, peer-reviewed publications and selected 208 of these based on their contributions to four key areas: virology; clinical characteristics, outcomes, therapeutic and preventive options; epidemiology and transmission; and animal interface and the search for natural hosts of MERS-CoV. Results: Dipeptidyl peptidase 4 (DPP4/CD26) was identified as the human receptor for MERS-CoV, and a variety of molecular and serological assays developed. Dromedary camels remain the only documented zoonotic source of human infection, but MERS-like CoVs have been detected in bat species globally, as well as in dromedary camels throughout the Middle East and Africa. However, despite evidence of camel-to-human MERS-CoV transmission and cases apparently related to camel contact, the source of many primary cases remains unknown. There have been sustained health care-associated human outbreaks in Saudi Arabia and South Korea, the latter originating from one traveler returning from the Middle East. Transmission mechanisms are poorly understood; for health care, this may include environmental contamination. Various potential therapeutics have been identified, but not yet evaluated in human clinical trials. At least one candidate vaccine has progressed to Phase I trials. Conclusions: There has been substantial MERS-CoV research since 2012, but significant knowledge gaps persist, especially in epidemiology and natural history of the infection. There have been few rigorous studies of baseline prevalence, transmission, and spectrum of disease. Terms such as “camel exposure” and the epidemiological relationships of cases should be clearly defined and standardized. We strongly recommend a shared and accessible registry or database. Coronaviruses will likely continue to emerge, arguing for a unified “One Health” approach.",2019 Mar 1,"['Dawson, Patrick', 'Malik, Mamunur Rahman', 'Parvez, Faruque', 'Morse, Stephen S.']",Vector Borne Zoonotic Dis,,,True
b463342e6ef8e2537568f371e7e15b3020f37ab8,PMC,"VaccHemInf project: protocol for a prospective cohort study of efficacy, safety and characterisation of immune functional response to vaccinations in haematopoietic stem cell transplant recipients",http://dx.doi.org/10.1136/bmjopen-2018-026093,PMC6398679,30772864,CC BY-NC,"INTRODUCTION: Immune reconstitution after haematopoietic stem cell transplantation (HSCT) is a complex and dynamic process, varying from a state of nearly complete immunosuppression to an expected full immune recovery. Specific vaccination guidelines recommend reimmunisation after HSCT but data regarding vaccine efficacy in this unique population are scarce. New immune functional assays could enable prediction of vaccine response in the setting of HSCT. METHODS AND ANALYSIS: A prospective, longitudinal single-centre cohort study of autologous and allogeneic HSCT recipients was designed in order to determine the vaccine response to five vaccine targets (pneumococcus, hepatitis B virus, Haemophilus Influenzae type b, tetanus and diphtheria) and to correlate it to immune function parameters. A workflow was set up to study serological response to vaccines and to describe the functional immune status of 100 HSCT recipients (50 autologous and 50 allogeneic) before and 3, 12 and 24 months after primary immunisation. At each time point, ‘basic’ immune status recording (serology, immunophenotyping of lymphocyte subsets by flow cytometry) will be assessed. The immune response will furthermore be evaluated before and 3 months after primary vaccination by two ex vivo immune functional assays assessing: (1) tumour necrosis factor alpha, interferon gamma production and host messenger RNA expression on whole-blood stimulation by lipopolysaccharide or Staphylococcus aureus enterotoxin B and (2) T-lymphocyte proliferation in response to a standard mitogen (phytohaemagglutinin) or to selected recall antigens. Reference intervals will be determined from a cohort of 30 healthy volunteers. This translational study will provide data describing vaccine response, immune functionality of HSCT recipients over time and will allow mapping HSCT recipients with regard to their immune function. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the institutional review board (no 69HCL17_0769). Results will be communicated at scientific meetings and submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03659773; Pre-results.",2019 Feb 15,"['Conrad, Anne', 'Boccard, Mathilde', 'Valour, Florent', 'Alcazer, Vincent', 'Tovar Sanchez, Aydee-Tamara', 'Chidiac, Christian', 'Laurent, Frédéric', 'Vanhems, Philippe', 'Salles, Gilles', 'Brengel-Pesce, Karen', 'Meunier, Boris', 'Trouillet-Assant, Sophie', 'Ader, Florence']",BMJ Open,,,True
a9eec435999ab4cd18d878153a834c72521ad604,PMC,"VaccHemInf project: protocol for a prospective cohort study of efficacy, safety and characterisation of immune functional response to vaccinations in haematopoietic stem cell transplant recipients",http://dx.doi.org/10.1136/bmjopen-2018-026093,PMC6398679,30772864,CC BY-NC,"INTRODUCTION: Immune reconstitution after haematopoietic stem cell transplantation (HSCT) is a complex and dynamic process, varying from a state of nearly complete immunosuppression to an expected full immune recovery. Specific vaccination guidelines recommend reimmunisation after HSCT but data regarding vaccine efficacy in this unique population are scarce. New immune functional assays could enable prediction of vaccine response in the setting of HSCT. METHODS AND ANALYSIS: A prospective, longitudinal single-centre cohort study of autologous and allogeneic HSCT recipients was designed in order to determine the vaccine response to five vaccine targets (pneumococcus, hepatitis B virus, Haemophilus Influenzae type b, tetanus and diphtheria) and to correlate it to immune function parameters. A workflow was set up to study serological response to vaccines and to describe the functional immune status of 100 HSCT recipients (50 autologous and 50 allogeneic) before and 3, 12 and 24 months after primary immunisation. At each time point, ‘basic’ immune status recording (serology, immunophenotyping of lymphocyte subsets by flow cytometry) will be assessed. The immune response will furthermore be evaluated before and 3 months after primary vaccination by two ex vivo immune functional assays assessing: (1) tumour necrosis factor alpha, interferon gamma production and host messenger RNA expression on whole-blood stimulation by lipopolysaccharide or Staphylococcus aureus enterotoxin B and (2) T-lymphocyte proliferation in response to a standard mitogen (phytohaemagglutinin) or to selected recall antigens. Reference intervals will be determined from a cohort of 30 healthy volunteers. This translational study will provide data describing vaccine response, immune functionality of HSCT recipients over time and will allow mapping HSCT recipients with regard to their immune function. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the institutional review board (no 69HCL17_0769). Results will be communicated at scientific meetings and submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03659773; Pre-results.",2019 Feb 15,"['Conrad, Anne', 'Boccard, Mathilde', 'Valour, Florent', 'Alcazer, Vincent', 'Tovar Sanchez, Aydee-Tamara', 'Chidiac, Christian', 'Laurent, Frédéric', 'Vanhems, Philippe', 'Salles, Gilles', 'Brengel-Pesce, Karen', 'Meunier, Boris', 'Trouillet-Assant, Sophie', 'Ader, Florence']",BMJ Open,,,True
79e536b521d16ae3e033e12d2a90e3c8729140e1,PMC,"VaccHemInf project: protocol for a prospective cohort study of efficacy, safety and characterisation of immune functional response to vaccinations in haematopoietic stem cell transplant recipients",http://dx.doi.org/10.1136/bmjopen-2018-026093,PMC6398679,30772864,CC BY-NC,"INTRODUCTION: Immune reconstitution after haematopoietic stem cell transplantation (HSCT) is a complex and dynamic process, varying from a state of nearly complete immunosuppression to an expected full immune recovery. Specific vaccination guidelines recommend reimmunisation after HSCT but data regarding vaccine efficacy in this unique population are scarce. New immune functional assays could enable prediction of vaccine response in the setting of HSCT. METHODS AND ANALYSIS: A prospective, longitudinal single-centre cohort study of autologous and allogeneic HSCT recipients was designed in order to determine the vaccine response to five vaccine targets (pneumococcus, hepatitis B virus, Haemophilus Influenzae type b, tetanus and diphtheria) and to correlate it to immune function parameters. A workflow was set up to study serological response to vaccines and to describe the functional immune status of 100 HSCT recipients (50 autologous and 50 allogeneic) before and 3, 12 and 24 months after primary immunisation. At each time point, ‘basic’ immune status recording (serology, immunophenotyping of lymphocyte subsets by flow cytometry) will be assessed. The immune response will furthermore be evaluated before and 3 months after primary vaccination by two ex vivo immune functional assays assessing: (1) tumour necrosis factor alpha, interferon gamma production and host messenger RNA expression on whole-blood stimulation by lipopolysaccharide or Staphylococcus aureus enterotoxin B and (2) T-lymphocyte proliferation in response to a standard mitogen (phytohaemagglutinin) or to selected recall antigens. Reference intervals will be determined from a cohort of 30 healthy volunteers. This translational study will provide data describing vaccine response, immune functionality of HSCT recipients over time and will allow mapping HSCT recipients with regard to their immune function. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the institutional review board (no 69HCL17_0769). Results will be communicated at scientific meetings and submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03659773; Pre-results.",2019 Feb 15,"['Conrad, Anne', 'Boccard, Mathilde', 'Valour, Florent', 'Alcazer, Vincent', 'Tovar Sanchez, Aydee-Tamara', 'Chidiac, Christian', 'Laurent, Frédéric', 'Vanhems, Philippe', 'Salles, Gilles', 'Brengel-Pesce, Karen', 'Meunier, Boris', 'Trouillet-Assant, Sophie', 'Ader, Florence']",BMJ Open,,,False
dcd5c4f4081c90fa1c4672cbe00246e62dcc440a,PMC,The Role of Autophagy in Eosinophilic Airway Inflammation,http://dx.doi.org/10.4110/in.2019.19.e5,PMC6399092,30838160,CC BY-NC,"Autophagy is a homeostatic mechanism that discards not only invading pathogens but also damaged organelles and denatured proteins via lysosomal degradation. Increasing evidence suggests a role for autophagy in inflammatory diseases, including infectious diseases, Crohn's disease, cystic fibrosis, and pulmonary hypertension. These studies suggest that modulating autophagy could be a novel therapeutic option for inflammatory diseases. Eosinophils are a major type of inflammatory cell that aggravates airway inflammatory diseases, particularly corticosteroid-resistant inflammation. The eosinophil count is a useful tool for assessing which patients may benefit from inhaled corticosteroid therapy. Recent studies demonstrate that autophagy plays a role in eosinophilic airway inflammatory diseases by promoting airway remodeling and loss of function. Genetic variant in the autophagy gene ATG5 is associated with asthma pathogenesis, and autophagy regulates apoptotic pathways in epithelial cells in individuals with chronic obstructive pulmonary disease. Moreover, autophagy dysfunction leads to severe inflammation, especially eosinophilic inflammation, in chronic rhinosinusitis. However, the mechanism underlying autophagy-mediated regulation of eosinophilic airway inflammation remains unclear. The aim of this review is to provide a general overview of the role of autophagy in eosinophilic airway inflammation. We also suggest that autophagy may be a new therapeutic target for airway inflammation, including that mediated by eosinophils.",2019 Feb 4,"['Lee, Jinju', 'Kim, Hun Sik']",Immune Netw,,,True
49fbca70a4e7e3018cab7eb445683c58fd06bce2,PMC,"Clinical and Epidemiologic Patterns of Chikungunya Virus Infection and Coincident Arboviral Disease in a School Cohort in Haiti, 2014–2015",http://dx.doi.org/10.1093/cid/ciy582,PMC6399436,30184178,CC BY-NC-ND,"BACKGROUND: Beginning in December 2013, an epidemic of chikungunya virus (CHIKV) infection spread across the Caribbean and into virtually all countries in the Western hemisphere, with >2.4 million cases reported through the end of 2017. METHODS: We monitored a cohort of school children in rural Haiti from May 2014, through February 2015, for occurrence of acute undifferentiated febrile illness, with clinical and laboratory data available for 252 illness episodes. RESULTS: Our findings document passage of the major CHIKV epidemic between May and July 2014, with 82 laboratory-confirmed cases. Subsequent peaks of febrile illness were found to incorporate smaller outbreaks of dengue virus serotypes 1 and 4 and Zika virus, with identification of additional infections with Mayaro virus, enterovirus D68, and coronavirus NL63. CHIKV and dengue virus serotype 1 infections were more common in older children, with a complaint of arthralgia serving as a significant predictor for infection with CHIKV (odds ratio, 16.2; 95% confidence interval, 8.0–34.4; positive predictive value, 66%; negative predictive value, 80%). CONCLUSIONS: Viral/arboviral infections were characterized by a pattern of recurrent outbreaks and case clusters, with the CHIKV epidemic representing just one of several arboviral agents moving through the population. Although clinical presentations of these agents are similar, arthralgias are highly suggestive of CHIKV infection.",2019 Mar 15,"['Ball, Jacob D', 'Elbadry, Maha A', 'Telisma, Taina', 'White, Sarah K', 'Chavannes, Sonese', 'Anilis, Marie Gina', 'Prosperi, Mattia', 'Cummings, Derek A T', 'Lednicky, John A', 'Morris, J Glenn', 'Beau de Rochars, Madsen']",Clin Infect Dis,,,True
df638f8a7a456418b116ca93f6b20b9cd8c7f791,PMC,Prevalence and outcomes of Guillain-Barré syndrome among pediatrics in Saudi Arabia: a 10-year retrospective study,http://dx.doi.org/10.2147/NDT.S187994,PMC6400135,30880987,CC BY-NC,"BACKGROUND: Guillain-Barré syndrome (GBS) is a progressive acute form of paralysis most probably secondary to an immune-mediated process. GBS among Saudis has been seldom investigated, which leaves both clinicians and researchers with scarcity in knowledge. Therefore, this study aims to assess the prevalence and clinical prognosis of GBS among pediatrics admitted with acute paralysis at a large healthcare facility in Riyadh, Saudi Arabia. METHODS: This retrospective study reviewed patients’ medical records between 2005 and 2015. Eligible cases were children (<14 years old) admitted to the hospital complaining of acute paralysis and later diagnosed with one form or variant of GBS. Pearson’s chi-square, Fisher’s exact test, and binary logistic regression were employed to analyze the collected data. RESULTS: The prevalence of GBS was 49%. The male-to-female ratio was 1.45:1. The mean ± standard deviation age was 7±3.7 years. There were 34 (69.4%) cases with progression to maximum paralysis in ≤2 weeks, while 15 (30.6%) cases occurred beyond 2 weeks. Males (n=24, 82.8%) were more likely to endure progression to maximum paralysis in ≤2 weeks after the disease onset, compared to females (n=10, 50%), P=0.014. All cases complaining of respiratory problems exhibited a progression to maximum paralysis in ≤2 weeks, compared to those with no respiratory problems, P=0.027. Residual paralysis at 60 days post disease onset was highly associated with GBS patients of age 8–14 years (n=15, 65.2%), compared to younger patients (n=8, 30.8%), P=0.016. Patients admitted in colder seasons (n=14, 63.6%) were more likely to suffer residual paralysis too, compared to those in warmer seasons (n=9, 33.3%), P=0.035. GBS cases who complained of facial weakness (n=9, 75%) and ocular abnormalities (n=10, 71.4%) were also more likely to endure residual paralysis at 60 days post disease onset, P=0.025 and P=0.03, respectively. CONCLUSION: Male gender could be a determinant of rapid progression to maximum paralysis, while the older age group in pediatrics is expected to endure residual paralysis at 60 days post disease onset. GBS can be accounted as a rare disease, especially in pediatrics, so confirmed cases should be investigated comprehensively for research purposes.",2019 Mar 1,"['Asiri, Safiyyah', 'Altwaijri, Waleed A', 'Ba-Armah, Duaa', 'Al Rumayyan, Ahmed', 'Alrifai, Muhammad T', 'Salam, Mahmoud', 'Almutairi, Adel F']",Neuropsychiatr Dis Treat,,,True
d539dd5b41a0186e1849f61cb6deaeb5e1cd855c,PMC,Middle East respiratory syndrome coronavirus (MERS-CoV),,PMC6402468,,CC BY-NC-SA,,2019 Feb,,Saudi Med J,,,False
b216cb3673df315302fa5747b0ad25ff7ba92162,PMC,Using research to prepare for outbreaks of severe acute respiratory infection,http://dx.doi.org/10.1136/bmjgh-2018-001061,PMC6407534,30899557,CC BY-NC,"Severe acute respiratory infections (SARI) remain one of the leading causes of mortality around the world in all age groups. There is large global variation in epidemiology, clinical management and outcomes, including mortality. We performed a short period observational data collection in critical care units distributed globally during regional peak SARI seasons from 1 January 2016 until 31 August 2017, using standardised data collection tools. Data were collected for 1 week on all admitted patients who met the inclusion criteria for SARI, with follow-up to hospital discharge. Proportions of patients across regions were compared for microbiology, management strategies and outcomes. Regions were divided geographically and economically according to World Bank definitions. Data were collected for 682 patients from 95 hospitals and 23 countries. The overall mortality was 9.5%. Of the patients, 21.7% were children, with case fatality proportions of 1% for those less than 5 years. The highest mortality was in those above 60 years, at 18.6%. Case fatality varied by region: East Asia and Pacific 10.2% (21 of 206), Sub-Saharan Africa 4.3% (8 of 188), South Asia 0% (0 of 35), North America 13.6% (25 of 184), and Europe and Central Asia 14.3% (9 of 63). Mortality in low-income and low-middle-income countries combined was 4% as compared with 14% in high-income countries. Organ dysfunction scores calculated on presentation in 560 patients where full data were available revealed Sequential Organ Failure Assessment (SOFA) scores on presentation were significantly associated with mortality and hospital length of stay. Patients in East Asia and Pacific (48%) and North America (24%) had the highest SOFA scores of >12. Multivariable analysis demonstrated that initial SOFA score and age were independent predictors of hospital survival. There was variability across regions and income groupings for the critical care management and outcomes of SARI. Intensive care unit-specific factors, geography and management features were less reliable than baseline severity for predicting ultimate outcome. These findings may help in planning future outbreak severity assessments, but more globally representative data are required.",2019 Feb 13,,BMJ Glob Health,,,True
e8c88bae765a67eb93e119820caa702994e13c1d,PMC,Imatinib-induced irreversible interstitial lung disease: A case report,http://dx.doi.org/10.1097/MD.0000000000014402,PMC6407980,30813141,CC BY-NC-ND,"RATIONALE: Imatinib mesylate (imatinib) is a classic tyrosine kinase inhibitor used to treat chronic myeloid leukemia. Although it is well tolerated by most patients and helps in the achievement of complete remission, a few rare imatinib-associated adverse effects such as pulmonary interstitial fibrosis have been reported. Because of its rareity, the clinical features of imatinib-induced interstitial lung disease (ILD) remain unclear. PATIENT CONCERNS: A 49-year-old Chinese man with chronic myeloid leukemia received oral treatment with imatinib and initially exhibited a good response. However, he presented with cough and fever 9 months after treatment initiation. DIAGNOSES: Pulmonary computed tomography indicated diffuse interstitial fibrosis in both lungs. All tests for possible infectious pathologies provided negative results. INTERVENTIONS: The patient was diagnosed with interstitial pneumonia and treated with antibiotics; however, there was no improvement. On the basis of a suspicion of imatinib-induced ILD, imatinib was discontinued and prednisone treatment was initiated. OUTCOMES: The patient's symptoms ameliorated with treatment, and imatinib was reintroduced. However, he developed cough and dyspnea again, and his treatment was switched to nilotinib as a second-line regimen. He was regularly monitored, and although his clinical symptoms ameliorated, computed tomography performed 29 months after he was diagnosed with ILD showed irreversible pulmonary interstitial fibrosis without progression. LESSONS: Clinicians should consider the possibility of severe irreversible ILD and carefully monitor patients receiving imatinib treatment.",2019 Feb 22,"['Zhang, Ping', 'Huang, Jingfeng', 'Jin, Fangfang', 'Pan, Jiaohai', 'Ouyang, Guifang']",Medicine (Baltimore),,,True
120be7888e94409082f16c372c818d66e558d33e,PMC,Acute fibrinous and organizing pneumonia: A case report,http://dx.doi.org/10.1097/MD.0000000000014537,PMC6408101,30813161,CC BY-NC,"RATIONALE: Acute fibrinous and organizing pneumonia (AFOP) is an uncommon type of acute lung injury associated with infection, connective tissue disorders, drug exposure, and hematologic malignancies. PATIENT CONCERNS: A 53-year-old female presented with intermittent fever, chills, and dry cough since 10 days. Chest computed tomography scan showed multiple bilateral patchy infiltrates. PPD skin test was positive but tuberculosis antibody test and T-SPOT were negative. DIAGNOSES: Histologic examination revealed massive fibrinous exudation with organization within alveolar spaces and scattered neutrophilic infiltrates, which was consistent with AFOP. INTERVENTIONS: This patient was treated with prednisolone therapy. OUTCOMES: Chest radiograph improvement and symptom improvement, including fever and respiratory symptoms, was observed after 2 week of oral prednisolone treatment. After 9-month of treatment, the patient was asymptomatic with stable disease and improved quality of life. LESSONS: AFOP has unique pathologic manifestations; however, the condition is liable to be misdiagnosed as community-acquired pneumonia ortuberculosis. Antibiotics are ineffective, while some patients show good response to glucocorticoid therapy.",2019 Feb 22,"['Wang, Yuanhui', 'Li, Yuwen', 'Wang, Qian', 'Zhang, Lili', 'Li, Jun', 'Zhu, Chuanlong']",Medicine (Baltimore),,,True
709c30173f5cfdd55b8636f71cf76d3788a0553d,PMC,Pneumocystis jirovecii pneumonia as an initial manifestation of hyper-IgM syndrome in an infant: A case report,http://dx.doi.org/10.1097/MD.0000000000014559,PMC6408131,30762803,CC BY-NC-ND,"RATIONALE: Pneumocystis jirovecii causes severe pneumonia in immunocompromised hosts. Human immunodeficiency virus infection, malignancy, solid organ or hematopoietic cell transplantation, and primary immune deficiency compose the risk factors for Pneumocystis pneumonia (PCP) in children, and PCP can be an initial clinical manifestation of primary immune deficiency. PATIENT CONCERNS: A 5-month-old infant presented with cyanosis and tachypnea. He had no previous medical or birth history suggesting primary immune deficiency. He was diagnosed with interstitial pneumonia on admission. DIAGNOSES: He was diagnosed with PCP, and further evaluations revealed underlying X-linked hyper-IgM syndrome. INTERVENTIONS: He was treated with trimethoprim/sulfamethoxazole for PCP, and eventually received allogeneic hematopoietic cell transplantation for hyper-IgM syndrome. OUTCOMES: Twenty months have passed after transplantation without severe complications. LESSONS: PCP should be considered in infants presenting with severe interstitial pneumonia even in the absence of evidence of immune deficiency. Primary immune deficiency should also be suspected in infants diagnosed with PCP.",2019 Feb 15,"['Kim, Danbi', 'Shin, Ju Ae', 'Han, Seung Beom', 'Chung, Nack-Gyun', 'Jeong, Dae Chul']",Medicine (Baltimore),,,True
9f7ffa3a1bbf4a6ad9e71f2377fb45564589d415,PMC,Necrotizing Enteritis Caused by Pharyngostomum cordatum Infection in a Stray Cat,http://dx.doi.org/10.3347/kjp.2019.57.1.17,PMC6409222,30840794,CC BY-NC,"A stray female cat of unknown age, presenting bright red watery diarrhea, was submitted to the Animal and Plant Quarantine Agency for diagnosis. In the small intestines extracted from the necropsied cat, numerous white oval-shaped organisms were firmly embedded in the mucosa and there was thickening of intestinal wall. Histopathological analysis revealed severe necrotizing enteritis, together with atrophied intestinal villi, exfoliated enterocytes, and parasitic worms. Recovered worms were identified as Pharyngostomum cordatum by morphological observation and genetic analysis. Although P. cordatum is known to occur widely in Korea, this is the first clinical description of an infection by P. cordatum causing severe feline enteritis.",2019 Feb 26,"['Kim, Ji-Hyeon', 'Lee, Kyunghyun', 'Sohn, Woon-Mok', 'Kim, Ha-Young', 'Lee, Yu-Ran', 'Choi, Eun-Jin', 'So, ByungJae', 'Jung, Ji-Youl']",Korean J Parasitol,,,True
a5f08604ffadbbd3a3759ba8c3b647913bc1c4b6,PMC,"Transmission of Respiratory Syncytial Virus Among Children Under 5 Years in Households of Rural Communities, the Philippines",http://dx.doi.org/10.1093/ofid/ofz045,PMC6411217,30882012,CC BY-NC-ND,"BACKGROUND: To develop a more effective vaccination strategy for reducing the impact of respiratory syncytial virus (RSV) infection, especially in young infants (<6 months old), it is necessary to understand the transmission dynamics of RSV. METHODS: We conducted a community-based prospective cohort study from 2014 to 2016 in Biliran Province, the Philippines, on children <5 years old. We collected nasopharyngeal swabs from symptomatic children with acute respiratory infection (ARI) during household visits and at health facilities. In households (n = 181) with RSV-positive ARI cases (RSV-ARI), we also identified ARI episodes among other children <5 years old in the same household. In addition, we determined the serial interval to estimate the basic reproduction number (R(0)), the average number of secondary cases generated by a single primary case. RESULTS: In the 181 households analyzed, we found 212 RSV-ARI in 152 households with a single case and 29 households with multiple cases, which included 29 1st RSV-ARI and 31 2nd RSV-ARI. We also found possible index cases among children <5 years old in the same household for 29.0% (18 of 62) of young infants with RSV-ARI. The estimated mean serial interval was 3.2 days, and R(0) was estimated to be 0.92–1.33 for RSV-A and 1.04–1.76 for RSV-B, which varied between different times (2014 and 2015) and places. CONCLUSIONS: Young infants are likely to acquire RSV infection from older children in the same household. Therefore, vaccination targeting older children might protect infants from RSV infection.",2019 Mar 11,"['Otomaru, Hirono', 'Kamigaki, Taro', 'Tamaki, Raita', 'Okamoto, Michiko', 'Alday, Portia Parian', 'Tan, Alvin Gue', 'Manalo, Joanna Ina', 'Segubre-Mercado, Edelwisa', 'Inobaya, Marianette Tawat', 'Tallo, Veronica', 'Lupisan, Socorro', 'Oshitani, Hitoshi']",Open Forum Infect Dis,,,True
95f7c797080ddb8d466a88443df62ea97f46d932,PMC,C3P3-G1: first generation of a eukaryotic artificial cytoplasmic expression system,http://dx.doi.org/10.1093/nar/gkz069,PMC6412113,30726994,CC BY-NC,"Most eukaryotic expression systems make use of host-cell nuclear transcriptional and post-transcriptional machineries. Here, we present the first generation of the chimeric cytoplasmic capping-prone phage polymerase (C3P3-G1) expression system developed by biological engineering, which generates capped and polyadenylated transcripts in host-cell cytoplasm by means of two components. First, an artificial single-unit chimeric enzyme made by fusing an mRNA capping enzyme and a DNA-dependent RNA polymerase. Second, specific DNA templates designed to operate with the C3P3-G1 enzyme, which encode for the transcripts and their artificial polyadenylation. This system, which can potentially be adapted to any in cellulo or in vivo eukaryotic expression applications, was optimized for transient expression in mammalian cells. C3P3-G1 shows promising results for protein production in Chinese Hamster Ovary (CHO-K1) cells. This work also provides avenues for enhancing the performances for next generation C3P3 systems.",2019 Mar 18,"['Jaïs, Philippe H', 'Decroly, Etienne', 'Jacquet, Eric', 'Le\xa0Boulch, Marine', 'Jaïs, Aurélien', 'Jean-Jean, Olivier', 'Eaton, Heather', 'Ponien, Prishila', 'Verdier, Fréderique', 'Canard, Bruno', 'Goncalves, Sergio', 'Chiron, Stéphane', 'Le\xa0Gall, Maude', 'Mayeux, Patrick', 'Shmulevitz, Maya']",Nucleic Acids Res,,,True
5cded487793694de49b640b3972285bfc8431cfb,PMC,Deciphering desirable immune responses from disease models with resistant and susceptible chickens,http://dx.doi.org/10.3382/ps/pey535,PMC6414032,30534980,CC BY-NC,"Coccidiosis and necrotic enteritis (NE) are among the most significant diseases affecting the poultry industry. These diseases have become more prominent in the wake of policies to reduce the use of antibiotics in animal production. This has led to more research focused on better understanding the immune system and its responses to pathogen challenge, and thus developing informed strategies to exploit immune responses that can support enhanced disease resistance and growth performance. Some chicken breeds and lines show greater resistance or susceptibility to various diseases, and thus these birds maybe able to shed light on immune processes or pathways that contribute to the more resistant/susceptible state. This review attempts to identify potentially important genes that show some consistency in (relative) up or downregulation in key tissues between the resistant and susceptible chickens. For coccidiosis and NE, relative downregulation of IL-10 and (slightly less consistently) upregulation of IFN-γ appear to be features of more resistant birds. Data for IFN-α, IL-12, and IL-17D are currently less consistent. Gene expression data from NE studies have identified some potentially interesting, perhaps less well understood, immune-related genes (e.g., TCF12, BCL2, IRF2, TRAF3, TAB3, etc.,) that maybe associated with the resistant and/or susceptible phenotype. Salmonella and Campylobacter are important foodborne pathogens harbored by the chicken intestinal tract, while infectious bursal disease and infectious bronchitis are also important viral diseases of poultry. We, therefore, consider whether there are consistent features from resistant/susceptible disease models with these pathogens that relate to findings from the coccidiosis and NE studies. It is not anticipated that ideal immune responses to these pathogens will be identical but rather that consistent elements maybe identified that could help inform breeding or alternative strategies to support general disease resistance and enhanced (and efficient) flock productivity.",2019 Apr 11,"['Broom, Leon J', 'Kogut, Michael H']",Poult Sci,,,True
c93f00ba900315d3b2ac23258d8ab75d63d366cf,PMC,Shiga toxin-producing Escherichia coli (STEC) isolated from fecal samples of African dromedary camels,http://dx.doi.org/10.1016/j.onehlt.2019.100087,PMC6416407,30911597,CC BY-NC-ND,"Shiga toxin-producing Escherichia coli (STEC) cause gastrointestinal illnesses including non-bloody or bloody diarrhoea, haemorrhagic colitis (HC), and the haemolytic uremic syndrome (HUS). To investigate the occurrence of STEC among grazing dromedaries from Kenya, E. coli isolated from fecal matter collected from 163 dromedaries on a large ranch were screened for the presence of stx1 and stx2. STEC strains were isolated and serotyped. Isolates were subjected to PCR for the subtyping of stx genes and for the detection of eae and ehx. In addition, whole genome sequencing (WGS) was carried out to detect further virulence genes and to determine the multilocus sequence types (MLST). Antimicrobial resistance profiles were determined by disk diffusion. STEC was isolated from 20 (12.3%) of the fecal samples. Thereof, nine (45%) isolates were STEC O156:H25, three (15%) isolates typed STEC O43:H2. The remaining isolates occurred as single serotypes or were O non-typeable. Eleven (55%) of the isolates harboured stx2a, nine (45%) eae, and 14 (70%) ehx, respectively. WGS revealed the presence of iss in 16 (80%), subAB in four (20%) and astA in two (10%) of the isolates, Furthermore, espA, tccP, nleA, nleB, tccP, and tir were found exclusively among STEC O156:H25. Eleven different sequence types (ST) were detected. The most prominent was ST300/ST5343, which comprised STEC O156:H25. All STEC isolates were pan susceptible to a panel of 16 antimicrobial agents. Overall, the results indicate that dromedary camels in Kenya may be reservoirs of STEC, including serotypes possessing virulence markers associated to disease in humans, such as STEC O156:H25. STEC in camels may represent a health hazard for humans with close contact to camels or to consumers of camel derived foodstuffs, such as unpasteurised camel milk.",2019 Mar 7,"['Baschera, Melinda', 'Cernela, Nicole', 'Stevens, Marc J.A.', 'Liljander, Anne', 'Jores, Jörg', 'Corman, Victor Max', 'Nüesch-Inderbinen, Magdalena', 'Stephan, Roger']",One Health,,,False
15d87194ff22d1a52809b2c2332aa3e11a6fcd4a,PMC,High Environmental Stability of Hepatitis B Virus and Inactivation Requirements for Chemical Biocides,http://dx.doi.org/10.1093/infdis/jiy620,PMC6420165,30358855,CC BY-NC-ND,"Hepatitis B virus (HBV) infection is considered a major public health problem worldwide, and a significant number of reports on nosocomial and occupational outbreaks have been reported. This systematic investigation of HBV stability and susceptibility to different antiseptics revealed that HBV infectivity was very stable, with a half-life of >22 days at 37°C. At 4°C, infectivity was barely reduced for up to 9 months. Different alcohols and commercially available hand antiseptics had a virucidal effect against HBV. We propose that very strict compliance with established hygienic guidelines should be mandatory to avoid and prevent HBV infections.",2019 Apr 1,"['Than, Thoa Thi', 'Jo, Eunji', 'Todt, Daniel', 'Nguyen, Phuong Hong', 'Steinmann, Jochen', 'Steinmann, Eike', 'Windisch, Marc P']",J Infect Dis,,,True
6daf14d0342bca1c7e6c9f52a65ba4fa3fe618ba,PMC,High Environmental Stability of Hepatitis B Virus and Inactivation Requirements for Chemical Biocides,http://dx.doi.org/10.1093/infdis/jiy620,PMC6420165,30358855,CC BY-NC-ND,"Hepatitis B virus (HBV) infection is considered a major public health problem worldwide, and a significant number of reports on nosocomial and occupational outbreaks have been reported. This systematic investigation of HBV stability and susceptibility to different antiseptics revealed that HBV infectivity was very stable, with a half-life of >22 days at 37°C. At 4°C, infectivity was barely reduced for up to 9 months. Different alcohols and commercially available hand antiseptics had a virucidal effect against HBV. We propose that very strict compliance with established hygienic guidelines should be mandatory to avoid and prevent HBV infections.",2019 Apr 1,"['Than, Thoa Thi', 'Jo, Eunji', 'Todt, Daniel', 'Nguyen, Phuong Hong', 'Steinmann, Jochen', 'Steinmann, Eike', 'Windisch, Marc P']",J Infect Dis,,,True
13531a593bf382e8e4f605622db4f7f2c6ef92a9,PMC,OAS-RNase L innate immune pathway mediates the cytotoxicity of a DNA-demethylating drug,http://dx.doi.org/10.1073/pnas.1815071116,PMC6421468,30814222,CC BY-NC-ND,"Drugs that reverse epigenetic silencing, such as the DNA methyltransferase inhibitor (DNMTi) 5-azacytidine (AZA), have profound effects on transcription and tumor cell survival. AZA is an approved drug for myelodysplastic syndromes and acute myeloid leukemia, and is under investigation for different solid malignant tumors. AZA treatment generates self, double-stranded RNA (dsRNA), transcribed from hypomethylated repetitive elements. Self dsRNA accumulation in DNMTi-treated cells leads to type I IFN production and IFN-stimulated gene expression. Here we report that cell death in response to AZA treatment occurs through the 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway. OASs are IFN-induced enzymes that synthesize the RNase L activator 2-5A in response to dsRNA. Cells deficient in RNase L or OAS1 to 3 are highly resistant to AZA, as are wild-type cells treated with a small-molecule inhibitor of RNase L. A small-molecule inhibitor of c-Jun NH(2)-terminal kinases (JNKs) also antagonizes RNase L-dependent cell death in response to AZA, consistent with a role for JNK in RNase L-induced apoptosis. In contrast, the rates of AZA-induced and RNase L-dependent cell death were increased by transfection of 2-5A, by deficiencies in ADAR1 (which edits and destabilizes dsRNA), PDE12 or AKAP7 (which degrade 2-5A), or by ionizing radiation (which induces IFN-dependent signaling). Finally, OAS1 expression correlates with AZA sensitivity in the NCI-60 set of tumor cell lines, suggesting that the level of OAS1 can be a biomarker for predicting AZA sensitivity of tumor cells. These studies may eventually lead to pharmacologic strategies for regulating the antitumor activity and toxicity of AZA and related drugs.",2019 Mar 12,"['Banerjee, Shuvojit', 'Gusho, Elona', 'Gaughan, Christina', 'Dong, Beihua', 'Gu, Xiaorong', 'Holvey-Bates, Elise', 'Talukdar, Manisha', 'Li, Yize', 'Weiss, Susan R.', 'Sicheri, Frank', 'Saunthararajah, Yogen', 'Stark, George R.', 'Silverman, Robert H.']",Proc Natl Acad Sci U S A,,,True
b1ac4363950bdd885496d03b7b035ca8bb7e2b3b,PMC,OAS-RNase L innate immune pathway mediates the cytotoxicity of a DNA-demethylating drug,http://dx.doi.org/10.1073/pnas.1815071116,PMC6421468,30814222,CC BY-NC-ND,"Drugs that reverse epigenetic silencing, such as the DNA methyltransferase inhibitor (DNMTi) 5-azacytidine (AZA), have profound effects on transcription and tumor cell survival. AZA is an approved drug for myelodysplastic syndromes and acute myeloid leukemia, and is under investigation for different solid malignant tumors. AZA treatment generates self, double-stranded RNA (dsRNA), transcribed from hypomethylated repetitive elements. Self dsRNA accumulation in DNMTi-treated cells leads to type I IFN production and IFN-stimulated gene expression. Here we report that cell death in response to AZA treatment occurs through the 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway. OASs are IFN-induced enzymes that synthesize the RNase L activator 2-5A in response to dsRNA. Cells deficient in RNase L or OAS1 to 3 are highly resistant to AZA, as are wild-type cells treated with a small-molecule inhibitor of RNase L. A small-molecule inhibitor of c-Jun NH(2)-terminal kinases (JNKs) also antagonizes RNase L-dependent cell death in response to AZA, consistent with a role for JNK in RNase L-induced apoptosis. In contrast, the rates of AZA-induced and RNase L-dependent cell death were increased by transfection of 2-5A, by deficiencies in ADAR1 (which edits and destabilizes dsRNA), PDE12 or AKAP7 (which degrade 2-5A), or by ionizing radiation (which induces IFN-dependent signaling). Finally, OAS1 expression correlates with AZA sensitivity in the NCI-60 set of tumor cell lines, suggesting that the level of OAS1 can be a biomarker for predicting AZA sensitivity of tumor cells. These studies may eventually lead to pharmacologic strategies for regulating the antitumor activity and toxicity of AZA and related drugs.",2019 Mar 12,"['Banerjee, Shuvojit', 'Gusho, Elona', 'Gaughan, Christina', 'Dong, Beihua', 'Gu, Xiaorong', 'Holvey-Bates, Elise', 'Talukdar, Manisha', 'Li, Yize', 'Weiss, Susan R.', 'Sicheri, Frank', 'Saunthararajah, Yogen', 'Stark, George R.', 'Silverman, Robert H.']",Proc Natl Acad Sci U S A,,,True
f0dd1cca2c2cc4ff4f1a37a74ca694382ba9eed4,PMC,Identification of Urinary CD44 and Prosaposin as Specific Biomarkers of Urinary Tract Infections in Children With Neurogenic Bladders,http://dx.doi.org/10.1177/1177271919835570,PMC6421595,30906192,CC BY-NC,"PURPOSE: Distinguishing urinary tract infection (UTI) from urinary tract colonization (UTC) in children with neurogenic bladders who require clean intermittent catheterization (CIC) is challenging. Our objective was to identify urinary proteins to distinguish UTI from UTC in CIC-dependent children that have potential to serve as objective markers of UTI. EXPERIMENTAL DESIGN: A total of 10 CIC-dependent children were included in the mass spectrometry analysis (UTI = 5, UTC = 5). Quantitative profiling of urine proteins with isobaric protein labeling was performed using tandem mass spectrometry. Candidate markers were normalized using a collective mixture of proteins from all samples. Relative quantitative abundance of proteins across all samples were compared. Proteins with >50% change in the average abundance were identified as proteins of interest, which were then measured using enzyme-linked immunosorbent assay (ELISA) in an additional 40 samples (no growth = 10, UTC = 15, UTI = 15). RESULTS: Mass spectrometry revealed 8 differentially expressed proteins. Of these, apolipoprotein D, alpha-amylase 2B, non-secretory ribonuclease, CD44 antigen, and prosaposin were measurable by ELISA. Concentrations of both CD44 and prosaposin were significantly higher in UTI, with area under the curves (AUCs) of 0.72 and 0.78, respectively. CONCLUSION: Urinary CD44 and prosaposin are candidate markers that may assist with the diagnosis of UTI in CIC-dependent children.",2019 Mar 15,"['Forster, Catherine S', 'Haffey, Wendy D', 'Bennett, Michael', 'Greis, Kenneth D', 'Devarajan, Prasad']",Biomark Insights,,,True
5407b1aabede9eeed76c59a7b890be9f513712b7,PMC,A simple and safe antibody neutralization assay based on polio pseudoviruses,http://dx.doi.org/10.1080/21645515.2018.1526553,PMC6422504,30273512,CC BY-NC-ND,"The evaluation of the immunogenicity of Sabin strain based Inactivated Poliovirus Vaccines (sIPV) necessitates the use of wild strains in neutralization assays to assess the potential cross-reactivity of antibodies. The live virus strains including wild and Sabin strains must be handled in level 3 biocontainment laboratories. To develop an alternative assay without the use of a live virus, we constructed Mahoney, MEF-1, and Saukett pseudovirions by inserting luciferase reporter genes into intact capsid proteins. Afterward, we developed a pseudovirus-based neutralization test (pNT) and evaluated for the specificity and reproducibility. We tested serum samples from a clinical trial on sIPV vaccines by pNT and compared the results with those obtained from conventional neutralization tests (cNT). A strong correlation was observed between two methods, with the correlation coefficients of all three types of IPV vaccines being greater than 0.82 (p < 0.0001). The Geometric Mean Titer (GMT) values obtained by pNT were approximately four times higher than that by cNT, revealing the better sensitivity of pNT. In conclusion, pNT is a safe, rapid and sensitive quantitative assay with the potential of being an alternative for the evaluation of the potency of polio vaccines.",2018 Oct 16,"['Jiang, Zheng', 'Liu, Guixiu', 'Guo-yang, Liao', 'Sun, Mingbo', 'Xu, Kangwei', 'Ying, Zhifang', 'Wang, Jianfeng', 'Li, Xuguang', 'Li, Changgui']",Hum Vaccin Immunother,,,True
17526c4d7ebc24e00acdd7c803eb97dd34980e41,PMC,Intratracheal Administration of siRNA Triggers mRNA Silencing in the Lung to Modulate T Cell Immune Response and Lung Inflammation,http://dx.doi.org/10.1016/j.omtn.2019.02.013,PMC6426712,30901578,CC BY-NC-ND,"Clinical application of siRNA-based therapeutics outside of the liver has been hindered by the inefficient delivery of siRNA effector molecules into extra-hepatic organs and cells of interest. To understand the parameters that enable RNAi activity in vivo, it is necessary to develop a systematic approach to identify which cells within a tissue are permissive to oligonucleotide internalization and activity. In the present study, we evaluate the distribution and activity within the lung of chemically stabilized siRNA to characterize cell-type tropism and structure-activity relationship. We demonstrate intratracheal delivery of fully modified siRNA for RNAi-mediated target knockdown in lung CD11c(+) cells (dendritic cells, alveolar macrophages) and alveolar epithelial cells. Finally, we use an allergen-induced model of lung inflammation to demonstrate the capacity of inhaled siRNA to induce target knockdown in dendritic cells and ameliorate lung pathology.",2019 Feb 26,"['Ng, Bruce', 'Cash-Mason, Tanesha', 'Wang, Yi', 'Seitzer, Jessica', 'Burchard, Julja', 'Brown, Duncan', 'Dudkin, Vadim', 'Davide, Joseph', 'Jadhav, Vasant', 'Sepp-Lorenzino, Laura', 'Cejas, Pedro J.']",Mol Ther Nucleic Acids,,,False
deae71f6c2acd88de567196bd0db6a426b759ff7,PMC,Intratracheal Administration of siRNA Triggers mRNA Silencing in the Lung to Modulate T Cell Immune Response and Lung Inflammation,http://dx.doi.org/10.1016/j.omtn.2019.02.013,PMC6426712,30901578,CC BY-NC-ND,"Clinical application of siRNA-based therapeutics outside of the liver has been hindered by the inefficient delivery of siRNA effector molecules into extra-hepatic organs and cells of interest. To understand the parameters that enable RNAi activity in vivo, it is necessary to develop a systematic approach to identify which cells within a tissue are permissive to oligonucleotide internalization and activity. In the present study, we evaluate the distribution and activity within the lung of chemically stabilized siRNA to characterize cell-type tropism and structure-activity relationship. We demonstrate intratracheal delivery of fully modified siRNA for RNAi-mediated target knockdown in lung CD11c(+) cells (dendritic cells, alveolar macrophages) and alveolar epithelial cells. Finally, we use an allergen-induced model of lung inflammation to demonstrate the capacity of inhaled siRNA to induce target knockdown in dendritic cells and ameliorate lung pathology.",2019 Feb 26,"['Ng, Bruce', 'Cash-Mason, Tanesha', 'Wang, Yi', 'Seitzer, Jessica', 'Burchard, Julja', 'Brown, Duncan', 'Dudkin, Vadim', 'Davide, Joseph', 'Jadhav, Vasant', 'Sepp-Lorenzino, Laura', 'Cejas, Pedro J.']",Mol Ther Nucleic Acids,,,False
8844e6a68b22d3f36ec69db175b660a8dd8a276b,PMC,Intratracheal Administration of siRNA Triggers mRNA Silencing in the Lung to Modulate T Cell Immune Response and Lung Inflammation,http://dx.doi.org/10.1016/j.omtn.2019.02.013,PMC6426712,30901578,CC BY-NC-ND,"Clinical application of siRNA-based therapeutics outside of the liver has been hindered by the inefficient delivery of siRNA effector molecules into extra-hepatic organs and cells of interest. To understand the parameters that enable RNAi activity in vivo, it is necessary to develop a systematic approach to identify which cells within a tissue are permissive to oligonucleotide internalization and activity. In the present study, we evaluate the distribution and activity within the lung of chemically stabilized siRNA to characterize cell-type tropism and structure-activity relationship. We demonstrate intratracheal delivery of fully modified siRNA for RNAi-mediated target knockdown in lung CD11c(+) cells (dendritic cells, alveolar macrophages) and alveolar epithelial cells. Finally, we use an allergen-induced model of lung inflammation to demonstrate the capacity of inhaled siRNA to induce target knockdown in dendritic cells and ameliorate lung pathology.",2019 Feb 26,"['Ng, Bruce', 'Cash-Mason, Tanesha', 'Wang, Yi', 'Seitzer, Jessica', 'Burchard, Julja', 'Brown, Duncan', 'Dudkin, Vadim', 'Davide, Joseph', 'Jadhav, Vasant', 'Sepp-Lorenzino, Laura', 'Cejas, Pedro J.']",Mol Ther Nucleic Acids,,,False
8e51b76492d9bb9fe3f64f80f5bdb3e29a8c5519,PMC,Guillain–Barré syndrome with unilateral peripheral facial and bulbar palsy in a child: A case report,http://dx.doi.org/10.1177/2050313X19838750,PMC6429638,30915222,CC BY-NC,"Guillain–Barré syndrome is characterized by progressive motor weakness, sensory changes, dysautonomia, and areflexia. Cranial nerve palsies are frequent in Guillain–Barré syndrome. Among cranial nerve palsies in Guillain–Barré syndrome, facial nerve palsy is the most common affecting around half of the cases. Facial palsy in Guillain–Barré syndrome is usually bilateral. We describe a pediatric Guillain–Barré syndrome variant presenting with unilateral peripheral facial palsy and dysphagia. A 5-year-old boy had progressive lower extremity weakness and pain 3 days prior to onset of unilateral peripheral facial palsy. On presentation, diagnosis of Guillain–Barré syndrome was supported by areflexia and albuminocytologic dissociation. His condition deteriorated with a decline in his respiratory effort and inability to handle secretions. He was given non-invasive ventilation to prevent worsening of his acute respiratory failure. Brain and spine magnetic resonance imaging scans showed enhancement of the left bulbar nerve complex and anterior and posterior cervical nerve roots with gadolinium. Treatment with intravenous immunoglobulin led to an uneventful clinical course with partial recovery within 2 weeks. In summary, Guillain–Barré syndrome should be considered as a possible cause of unilateral peripheral facial palsy. Guillain–Barré syndrome patients with facial nerve and bulbar palsy require close monitoring as they are at risk of developing acute respiratory failure. Early intervention with intravenous immunoglobulin may benefit these patients. Magnetic resonance imaging findings may lend support to early intervention.",2019 Mar 21,"['Sharma, Kamal', 'Tengsupakul, Supatida', 'Sanchez, Omar', 'Phaltas, Rozaleen', 'Maertens, Paul']",SAGE Open Med Case Rep,,,True
2272b370fe7b1e730af1659f9e3099c451b1a21d,PMC,A SimpleProbe(®) real‐time PCR assay for differentiating the canine parvovirus type 2 genotype,http://dx.doi.org/10.1002/jcla.22654,PMC6430354,30168193,CC BY-NC,"BACKGROUND: Canine parvovirus type 2 (CPV‐2) causes an important canine viral disease worldwide. CPV‐2 belongs to the Protoparvovirus genus in the family Parvoviridae. An amino acid change at position 426 of the VP2 protein differentiate types of CPV‐2, designated as CPV‐2a (Asn), CPV‐2b (Asp), and CPV‐2c (Glu). In this study, we compared CPV‐2 genotyping results obtained by SimpleProbe(®) real‐time PCR and DNA sequencing analysis to identify the accuracy and sensitivity of these methods. METHODS: One hundred rectal swabs were collected from CPV‐2 naturally infected dogs from 2015 to 2017 at the Animal Disease Diagnostic Center, National Pingtung University of Science and Technology. CPV‐2 genotyping was performed by SimpleProbe(®) real‐time PCR and DNA sequencing to compare results. RESULTS: CPV‐2a (n = 23), 2b (n = 6) and 2c (n = 71) genotyping results obtained by both techniques were identical with specificity of 100% for SimpleProbe(®) assay. In the SimpleProbe(®) assay, amplifying the DNAs prepared from the clinical specimens showed three distinct melting curve peaks. CPV‐2b had the highest melting peak of 57.8°C (CI 95%: 57.7‐58.5°C) followed by CPV‐2c with a slightly lower melting peak of 52.3°C (CI 95%: 52.2‐53.2°C) and CPV‐2a with the lowest peak of 50.2°C (CI 95%: 50.1‐50.5°C). CONCLUSION: This study developed a novel method for genotyping CPV‐2 strains using the SimpleProbe(®) real‐time PCR assay. This assay is a reliable and sensitive tool for differentiating between the CPV‐2a, 2b and 2c and this technique can be used for molecular CPV‐2 epidemiology studies.",2018 Aug 31,"['Hoang, Minh', 'Wu, Hung‐Yi', 'Lien, Ying‐Xiu', 'Chiou, Ming‐Tang', 'Lin, Chao‐Nan']",J Clin Lab Anal,,,True
53c5b444db5bde8e975a22df9e3c80250e8ad3d1,PMC,Disease features of equine coronavirus and enteric salmonellosis are similar in horses,http://dx.doi.org/10.1111/jvim.15386,PMC6430874,30632200,CC BY-NC,"BACKGROUND: Equine coronavirus (ECoV) is an emerging pathogen associated with fever and enteric disease in adult horses. Clinical features of ECoV infection have been described, but no study has compared these features to those of Salmonella infections. OBJECTIVES: Compare the clinical features of ECoV infection with enteric salmonellosis and establish a disease signature to increase clinical suspicion of ECoV infection in adult horses. ANIMALS: Forty‐three horses >1 year of age with results of CBC, serum biochemistry, and fecal diagnostic testing for ECoV and Salmonella spp. METHODS: Medical records of horses presented to the North Carolina State University Equine and Farm Animal Veterinary Center (2003‐016) were retrospectively reviewed. Horses were divided into 3 groups based on fecal diagnostic test results: ECoV‐positive, Salmonella‐positive, or unknown diagnosis (UNK). Time of year presented, clinical signs, CBC, and serum biochemistry test results were recorded. Data were analyzed by 1‐way analysis of variance, Kruskal‐Wallis test, or Fisher's exact test with significance set at P < .05. RESULTS: Most common presenting complaints were fever and colic and were similar across groups. Horses with ECoV had significantly decreased neutrophil counts when compared to those with no diagnosis but were not different from horses with Salmonella. Horses with Salmonella had significantly lower mean leukocyte counts compared to those with UNK. No significant differences were found among groups for any other examined variable. CONCLUSIONS AND CLINICAL IMPORTANCE: Equine coronavirus and Salmonella infections share clinical features, suggesting both diseases should be differential diagnoses for horses with fever and enteric clinical signs.",2019 Jan 10 Mar-Apr,"['Manship, Arlie J.', 'Blikslager, Anthony T.', 'Elfenbein, Johanna R.']",J Vet Intern Med,,,True
0f8e65d8901e2bfe93d4d004f551f8620f4c9795,PMC,Disease features of equine coronavirus and enteric salmonellosis are similar in horses,http://dx.doi.org/10.1111/jvim.15386,PMC6430874,30632200,CC BY-NC,"BACKGROUND: Equine coronavirus (ECoV) is an emerging pathogen associated with fever and enteric disease in adult horses. Clinical features of ECoV infection have been described, but no study has compared these features to those of Salmonella infections. OBJECTIVES: Compare the clinical features of ECoV infection with enteric salmonellosis and establish a disease signature to increase clinical suspicion of ECoV infection in adult horses. ANIMALS: Forty‐three horses >1 year of age with results of CBC, serum biochemistry, and fecal diagnostic testing for ECoV and Salmonella spp. METHODS: Medical records of horses presented to the North Carolina State University Equine and Farm Animal Veterinary Center (2003‐016) were retrospectively reviewed. Horses were divided into 3 groups based on fecal diagnostic test results: ECoV‐positive, Salmonella‐positive, or unknown diagnosis (UNK). Time of year presented, clinical signs, CBC, and serum biochemistry test results were recorded. Data were analyzed by 1‐way analysis of variance, Kruskal‐Wallis test, or Fisher's exact test with significance set at P < .05. RESULTS: Most common presenting complaints were fever and colic and were similar across groups. Horses with ECoV had significantly decreased neutrophil counts when compared to those with no diagnosis but were not different from horses with Salmonella. Horses with Salmonella had significantly lower mean leukocyte counts compared to those with UNK. No significant differences were found among groups for any other examined variable. CONCLUSIONS AND CLINICAL IMPORTANCE: Equine coronavirus and Salmonella infections share clinical features, suggesting both diseases should be differential diagnoses for horses with fever and enteric clinical signs.",2019 Jan 10 Mar-Apr,"['Manship, Arlie J.', 'Blikslager, Anthony T.', 'Elfenbein, Johanna R.']",J Vet Intern Med,,,False
22ad1016b7afc7b517f0e6ea9fe27984f582908f,PMC,Disease features of equine coronavirus and enteric salmonellosis are similar in horses,http://dx.doi.org/10.1111/jvim.15386,PMC6430874,30632200,CC BY-NC,"BACKGROUND: Equine coronavirus (ECoV) is an emerging pathogen associated with fever and enteric disease in adult horses. Clinical features of ECoV infection have been described, but no study has compared these features to those of Salmonella infections. OBJECTIVES: Compare the clinical features of ECoV infection with enteric salmonellosis and establish a disease signature to increase clinical suspicion of ECoV infection in adult horses. ANIMALS: Forty‐three horses >1 year of age with results of CBC, serum biochemistry, and fecal diagnostic testing for ECoV and Salmonella spp. METHODS: Medical records of horses presented to the North Carolina State University Equine and Farm Animal Veterinary Center (2003‐016) were retrospectively reviewed. Horses were divided into 3 groups based on fecal diagnostic test results: ECoV‐positive, Salmonella‐positive, or unknown diagnosis (UNK). Time of year presented, clinical signs, CBC, and serum biochemistry test results were recorded. Data were analyzed by 1‐way analysis of variance, Kruskal‐Wallis test, or Fisher's exact test with significance set at P < .05. RESULTS: Most common presenting complaints were fever and colic and were similar across groups. Horses with ECoV had significantly decreased neutrophil counts when compared to those with no diagnosis but were not different from horses with Salmonella. Horses with Salmonella had significantly lower mean leukocyte counts compared to those with UNK. No significant differences were found among groups for any other examined variable. CONCLUSIONS AND CLINICAL IMPORTANCE: Equine coronavirus and Salmonella infections share clinical features, suggesting both diseases should be differential diagnoses for horses with fever and enteric clinical signs.",2019 Jan 10 Mar-Apr,"['Manship, Arlie J.', 'Blikslager, Anthony T.', 'Elfenbein, Johanna R.']",J Vet Intern Med,,,False
7afb40ff1e8710f31b4805249e6e6fcce6467e96,PMC,Evaluation of equine coronavirus fecal shedding among hospitalized horses,http://dx.doi.org/10.1111/jvim.15449,PMC6430884,30788861,CC BY-NC,"BACKGROUND: Currently, diagnosis of equine coronavirus (ECoV) relies on the exclusion of other infectious causes of enteric disease along with molecular detection of ECoV in feces or tissue. Although this approach is complete, it is costly and may not always be achievable. OBJECTIVE: We hypothesized that the overall fecal shedding of ECoV in hospitalized horses is low. Our objective was to determine whether systemically healthy horses and horses with gastrointestinal disorders shed ECoV in their feces at the time of admission to a referral hospital and after 48 hours of stress associated with hospitalization. ANIMALS: One‐hundred thirty adult horses admitted to the Washington State University Veterinary Teaching Hospital for gastrointestinal disease (n = 65) or for imaging under anesthesia (n = 65) that were hospitalized for 48 hours. Owner consent was obtained before sampling. METHODS: Fecal samples were collected at admission and 48 hours later. Polymerase chain reaction (PCR) for ECoV and electron microscopy (EM) were performed on all samples. RESULTS: Only 1 of 258 fecal samples was PCR‐positive for ECoV. Electron microscopy identified ECoV‐like particles in 9 of 258 samples, parvovirus‐like particles in 4 of 258 samples, and rotavirus‐like particles in 1 of 258 samples. CONCLUSIONS AND CLINICAL IMPORTANCE: The presence of ECoV in feces of hospitalized adult horses was low. Thus, fecal samples that are PCR‐positive for ECoV in adult horses that have clinical signs consistent with this viral infection are likely to be of diagnostic relevance. The clinical relevance of the viruses observed using EM remains to be investigated.",2019 Feb 20 Mar-Apr,"['Sanz, Macarena G.', 'Kwon, SoYoung', 'Pusterla, Nicola', 'Gold, Jenifer R.', 'Bain, Fairfield', 'Evermann, Jim']",J Vet Intern Med,,,True
9c4c3663078fac75ec89955444e1bed1f069e751,PMC,Fungi in respiratory samples of horses with inflammatory airway disease,http://dx.doi.org/10.1111/jvim.15397,PMC6430897,30576012,CC BY-NC,"BACKGROUND: Fungi contribute to the inflammatory response of lungs in horses with recurrent airway obstruction and in some forms of asthma in humans. The role of fungi in inflammatory airway disease (IAD) has not been assessed. OBJECTIVES: Evaluate the prevalence of fungi in the respiratory samples of horses diagnosed with IAD, describe clinical signs associated with the presence of fungi in respiratory samples, and assess the risk factors associated with IAD and with the presence of fungi in the airways. ANIMALS: Seven‐hundred thirty‐one active horses referred to a specialized ambulatory practice for signs of respiratory disease or poor performance. METHODS: A prospective observational study was performed, collecting clinical data, environmental conditions, and results of a tracheal wash (TW; cytology, fungal culture, and bacterial culture), and bronchoalveolar lavage (cytology). RESULTS: A positive fungal culture was obtained in 55% (402/731) of horses. Horses with fungal elements observed on the TW cytology had 2 times greater chance of having IAD than horses without fungi (odds ratio [OR] = 2.1; 95% CI 1.08‐3.33; P = .0003). Risks of being diagnosed with IAD and likelihood of fungi in TW were higher when horses were bedded on straw (OR = 2.0; 95% CI 1.2‐3.2 and OR = 1.9; 95% CI 1.3‐2.6, respectively) or fed dry hay (OR = 2.7; 95% CI 1.7‐4.4 and OR = 2.6; 95% CI 1.6‐3.4, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Horses inhaling aerosolized fungal particles are at a significantly higher risk of developing IAD. The type of bedding and forage represent significant risk factors for IAD and fungal contamination of equine airways.",2019 Dec 21 Mar-Apr,"['Dauvillier, Julie', 'ter Woort, Fe', 'van Erck‐Westergren, Emmanuelle']",J Vet Intern Med,,,True
1c027ab6a3c4c10fe054c80c4ac3b93aaacbf802,PMC,RESEARCH COMMUNICATIONS OF THE 28th ECVIM‐CA CONGRESS,http://dx.doi.org/10.1111/jvim.15372,PMC6430903,,CC BY-NC,,2019 Dec 19 Mar-Apr,,J Vet Intern Med,,,False
f17b881cc20dbd7330c1b396037fc872a4ff47ee,PMC,"Plasma citrulline, arginine, nitric oxide, and blood ammonia levels in neonatal calves with acute diarrhea",http://dx.doi.org/10.1111/jvim.15459,PMC6430905,30788867,CC BY-NC,"BACKGROUND: Plasma citrulline (CIT) concentration is considered to be a reliable marker of functional enterocyte mass, primarily in humans. However, information about CIT levels along with related metabolites, arginine (ARG), nitric oxide (NO), and ammonia in neonatal calves are lacking. OBJECTIVES: To compare plasma CIT, ARG, NO, and whole blood ammonia concentrations in neonatal calves with acute diarrhea with those in healthy calves and to assess their possible relationships with diarrhea‐related criteria. ANIMALS: Seventy neonatal calves (60 with acute diarrhea and 10 healthy). METHODS: Observational case‐control study. Diarrheic calves were classified into subgroups on the basis of etiology, severity of diarrhea, degree of dehydration, and systemic inflammatory response syndrome (SIRS) status. Plasma CIT and ARG concentrations were measured by liquid chromatography/tandem mass spectrometry. RESULTS: Plasma CIT (median [range]: 67.5 [61.9‐75.4] vs 30.1 [15.0‐56.1] μmol/L) and ARG (170.7 [148.5‐219.5] vs 106.1 [54.4‐190.7] μmol/L) were lower and plasma NO (4.42 [3.29‐5.58] vs 6.78 [5.29‐8.92] μM) and blood ammonia concentrations (28.7 [26.1‐36.9] vs 59.8 [34.6‐99.5] μmol/L) were higher in the neonatal calves with diarrhea (P < .001). Plasma CIT (β = −0.29, P = .02), ARG (β = −0.33, P = .01), NO (β = 0.55, P < .001), and blood ammonia (β = 0.63, P <.001) were affected by SIRS status. Except for ammonia (0.52), the effects sizes for severity of diarrhea and degree of dehydration were small (ηp2 ≤ 0.45) for CIT, ARG, and NO. CONCLUSIONS AND CLINICAL IMPORTANCE: The changes in these variables might have diagnostic, prognostic, and therapeutic value in diarrheic neonatal calves.",2019 Feb 20 Mar-Apr,"['Gultekin, Mehmet', 'Voyvoda, Huseyin', 'Ural, Kerem', 'Erdogan, Hasan', 'Balikci, Canberk', 'Gultekin, Gamze']",J Vet Intern Med,,,True
3be1720b6058d0560bd1a90d3a1e42e4a901504b,PMC,"Plasma citrulline, arginine, nitric oxide, and blood ammonia levels in neonatal calves with acute diarrhea",http://dx.doi.org/10.1111/jvim.15459,PMC6430905,30788867,CC BY-NC,"BACKGROUND: Plasma citrulline (CIT) concentration is considered to be a reliable marker of functional enterocyte mass, primarily in humans. However, information about CIT levels along with related metabolites, arginine (ARG), nitric oxide (NO), and ammonia in neonatal calves are lacking. OBJECTIVES: To compare plasma CIT, ARG, NO, and whole blood ammonia concentrations in neonatal calves with acute diarrhea with those in healthy calves and to assess their possible relationships with diarrhea‐related criteria. ANIMALS: Seventy neonatal calves (60 with acute diarrhea and 10 healthy). METHODS: Observational case‐control study. Diarrheic calves were classified into subgroups on the basis of etiology, severity of diarrhea, degree of dehydration, and systemic inflammatory response syndrome (SIRS) status. Plasma CIT and ARG concentrations were measured by liquid chromatography/tandem mass spectrometry. RESULTS: Plasma CIT (median [range]: 67.5 [61.9‐75.4] vs 30.1 [15.0‐56.1] μmol/L) and ARG (170.7 [148.5‐219.5] vs 106.1 [54.4‐190.7] μmol/L) were lower and plasma NO (4.42 [3.29‐5.58] vs 6.78 [5.29‐8.92] μM) and blood ammonia concentrations (28.7 [26.1‐36.9] vs 59.8 [34.6‐99.5] μmol/L) were higher in the neonatal calves with diarrhea (P < .001). Plasma CIT (β = −0.29, P = .02), ARG (β = −0.33, P = .01), NO (β = 0.55, P < .001), and blood ammonia (β = 0.63, P <.001) were affected by SIRS status. Except for ammonia (0.52), the effects sizes for severity of diarrhea and degree of dehydration were small (ηp2 ≤ 0.45) for CIT, ARG, and NO. CONCLUSIONS AND CLINICAL IMPORTANCE: The changes in these variables might have diagnostic, prognostic, and therapeutic value in diarrheic neonatal calves.",2019 Feb 20 Mar-Apr,"['Gultekin, Mehmet', 'Voyvoda, Huseyin', 'Ural, Kerem', 'Erdogan, Hasan', 'Balikci, Canberk', 'Gultekin, Gamze']",J Vet Intern Med,,,False
647f5293613f9be827c37bb609d3248db9889d78,PMC,ACVIM consensus statement on the diagnosis of immune‐mediated hemolytic anemia in dogs and cats,http://dx.doi.org/10.1111/jvim.15441,PMC6430921,30806491,CC BY-NC,"Immune‐mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune‐mediated erythrocyte destruction, and adverse consequences of long‐term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence‐based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors.",2019 Feb 26 Mar-Apr,"['Garden, Oliver A.', 'Kidd, Linda', 'Mexas, Angela M.', 'Chang, Yu‐Mei', 'Jeffery, Unity', 'Blois, Shauna L.', 'Fogle, Jonathan E.', 'MacNeill, Amy L.', 'Lubas, George', 'Birkenheuer, Adam', 'Buoncompagni, Simona', 'Dandrieux, Julien R. S.', 'Di Loria, Antonio', 'Fellman, Claire L.', 'Glanemann, Barbara', 'Goggs, Robert', 'Granick, Jennifer L.', 'LeVine, Dana N.', 'Sharp, Claire R.', 'Smith‐Carr, Saralyn', 'Swann, James W.', 'Szladovits, Balazs']",J Vet Intern Med,,,True
94a10870a3585f2d71edeb6de9c2235d59f8bae4,PMC,ACVIM consensus statement on the diagnosis of immune‐mediated hemolytic anemia in dogs and cats,http://dx.doi.org/10.1111/jvim.15441,PMC6430921,30806491,CC BY-NC,"Immune‐mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune‐mediated erythrocyte destruction, and adverse consequences of long‐term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence‐based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors.",2019 Feb 26 Mar-Apr,"['Garden, Oliver A.', 'Kidd, Linda', 'Mexas, Angela M.', 'Chang, Yu‐Mei', 'Jeffery, Unity', 'Blois, Shauna L.', 'Fogle, Jonathan E.', 'MacNeill, Amy L.', 'Lubas, George', 'Birkenheuer, Adam', 'Buoncompagni, Simona', 'Dandrieux, Julien R. S.', 'Di Loria, Antonio', 'Fellman, Claire L.', 'Glanemann, Barbara', 'Goggs, Robert', 'Granick, Jennifer L.', 'LeVine, Dana N.', 'Sharp, Claire R.', 'Smith‐Carr, Saralyn', 'Swann, James W.', 'Szladovits, Balazs']",J Vet Intern Med,,,False
a0c48f8d2c0e2e43df2fc1f904fc97aa4d0584ac,PMC,ACVIM consensus statement on the diagnosis of immune‐mediated hemolytic anemia in dogs and cats,http://dx.doi.org/10.1111/jvim.15441,PMC6430921,30806491,CC BY-NC,"Immune‐mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune‐mediated erythrocyte destruction, and adverse consequences of long‐term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence‐based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors.",2019 Feb 26 Mar-Apr,"['Garden, Oliver A.', 'Kidd, Linda', 'Mexas, Angela M.', 'Chang, Yu‐Mei', 'Jeffery, Unity', 'Blois, Shauna L.', 'Fogle, Jonathan E.', 'MacNeill, Amy L.', 'Lubas, George', 'Birkenheuer, Adam', 'Buoncompagni, Simona', 'Dandrieux, Julien R. S.', 'Di Loria, Antonio', 'Fellman, Claire L.', 'Glanemann, Barbara', 'Goggs, Robert', 'Granick, Jennifer L.', 'LeVine, Dana N.', 'Sharp, Claire R.', 'Smith‐Carr, Saralyn', 'Swann, James W.', 'Szladovits, Balazs']",J Vet Intern Med,,,False
ef1efc8936a33b9ffb3a691071a4372f9ee173f6,PMC,ACVIM consensus statement on the diagnosis of immune‐mediated hemolytic anemia in dogs and cats,http://dx.doi.org/10.1111/jvim.15441,PMC6430921,30806491,CC BY-NC,"Immune‐mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune‐mediated erythrocyte destruction, and adverse consequences of long‐term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence‐based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors.",2019 Feb 26 Mar-Apr,"['Garden, Oliver A.', 'Kidd, Linda', 'Mexas, Angela M.', 'Chang, Yu‐Mei', 'Jeffery, Unity', 'Blois, Shauna L.', 'Fogle, Jonathan E.', 'MacNeill, Amy L.', 'Lubas, George', 'Birkenheuer, Adam', 'Buoncompagni, Simona', 'Dandrieux, Julien R. S.', 'Di Loria, Antonio', 'Fellman, Claire L.', 'Glanemann, Barbara', 'Goggs, Robert', 'Granick, Jennifer L.', 'LeVine, Dana N.', 'Sharp, Claire R.', 'Smith‐Carr, Saralyn', 'Swann, James W.', 'Szladovits, Balazs']",J Vet Intern Med,,,True
7c5c81226bc5cf7d5506fb44115d566dfc3fa1db,PMC,ACVIM consensus statement on the diagnosis of immune‐mediated hemolytic anemia in dogs and cats,http://dx.doi.org/10.1111/jvim.15441,PMC6430921,30806491,CC BY-NC,"Immune‐mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune‐mediated erythrocyte destruction, and adverse consequences of long‐term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence‐based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors.",2019 Feb 26 Mar-Apr,"['Garden, Oliver A.', 'Kidd, Linda', 'Mexas, Angela M.', 'Chang, Yu‐Mei', 'Jeffery, Unity', 'Blois, Shauna L.', 'Fogle, Jonathan E.', 'MacNeill, Amy L.', 'Lubas, George', 'Birkenheuer, Adam', 'Buoncompagni, Simona', 'Dandrieux, Julien R. S.', 'Di Loria, Antonio', 'Fellman, Claire L.', 'Glanemann, Barbara', 'Goggs, Robert', 'Granick, Jennifer L.', 'LeVine, Dana N.', 'Sharp, Claire R.', 'Smith‐Carr, Saralyn', 'Swann, James W.', 'Szladovits, Balazs']",J Vet Intern Med,,,True
d6f4597aa9fb819ab0adf5c68601e967ef9970e5,PMC,ACVIM consensus statement on the diagnosis of immune‐mediated hemolytic anemia in dogs and cats,http://dx.doi.org/10.1111/jvim.15441,PMC6430921,30806491,CC BY-NC,"Immune‐mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune‐mediated erythrocyte destruction, and adverse consequences of long‐term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence‐based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors.",2019 Feb 26 Mar-Apr,"['Garden, Oliver A.', 'Kidd, Linda', 'Mexas, Angela M.', 'Chang, Yu‐Mei', 'Jeffery, Unity', 'Blois, Shauna L.', 'Fogle, Jonathan E.', 'MacNeill, Amy L.', 'Lubas, George', 'Birkenheuer, Adam', 'Buoncompagni, Simona', 'Dandrieux, Julien R. S.', 'Di Loria, Antonio', 'Fellman, Claire L.', 'Glanemann, Barbara', 'Goggs, Robert', 'Granick, Jennifer L.', 'LeVine, Dana N.', 'Sharp, Claire R.', 'Smith‐Carr, Saralyn', 'Swann, James W.', 'Szladovits, Balazs']",J Vet Intern Med,,,True
2cf45a5a4224dbf38d537eace1f6d49327e3487d,PMC,ACVIM consensus statement on the diagnosis of immune‐mediated hemolytic anemia in dogs and cats,http://dx.doi.org/10.1111/jvim.15441,PMC6430921,30806491,CC BY-NC,"Immune‐mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune‐mediated erythrocyte destruction, and adverse consequences of long‐term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence‐based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors.",2019 Feb 26 Mar-Apr,"['Garden, Oliver A.', 'Kidd, Linda', 'Mexas, Angela M.', 'Chang, Yu‐Mei', 'Jeffery, Unity', 'Blois, Shauna L.', 'Fogle, Jonathan E.', 'MacNeill, Amy L.', 'Lubas, George', 'Birkenheuer, Adam', 'Buoncompagni, Simona', 'Dandrieux, Julien R. S.', 'Di Loria, Antonio', 'Fellman, Claire L.', 'Glanemann, Barbara', 'Goggs, Robert', 'Granick, Jennifer L.', 'LeVine, Dana N.', 'Sharp, Claire R.', 'Smith‐Carr, Saralyn', 'Swann, James W.', 'Szladovits, Balazs']",J Vet Intern Med,,,True
e18ac727e1edc13aeab67e5d458ee00a190ace7b,PMC,Trends and Patterns of Burden of Disease and Injuries in Korea Using Disability-Adjusted Life Years,http://dx.doi.org/10.3346/jkms.2019.34.e75,PMC6434149,30923488,CC BY-NC,"BACKGROUND: It is extremely important to objectively take a view of population health to provide useful information to decision makers, health-sector leaders, researchers, and informed citizens. This study aims to examine the burden of disease in Korea as of 2015, and to study how the burden of disease changes with the passage of time. METHODS: We used results from the Korean National Burden of Disease and Injuries Study 2015 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive disability-adjusted life years (DALYs) by gender and age groups from 2007 to 2015. DALYs were calculated as the sum of the years of life lost (YLLs) and the years lived with disability (YLDs). RESULTS: In 2015, the burden of disease for Korean people was calculated at 29,476 DALYs per 100,000 population. DALYs caused by low back pain were the highest, followed by diabetes mellitus and chronic obstructive pulmonary disease. The burden of disease showed a consistently increasing trend from 2007 to 2015. Although YLLs have been on the decrease since 2011, the increase in YLDs has contributed to the overall rise in DALYs. The DALYs per 100,000 population in 2015 increased by 28.1% compared to 2007. CONCLUSION: As for the diseases for which the burden of disease is substantially increasing, it is needed to establish appropriate policies in a timely manner. The results of this study are expected to be the basis for prioritizing public health and health care policies in Korea.",2019 Mar 5,"['Kim, Young-Eun', 'Park, Hyesook', 'Jo, Min-Woo', 'Oh, In-Hwan', 'Go, Dun-Sol', 'Jung, Jaehun', 'Yoon, Seok-Jun']",J Korean Med Sci,,,True
7220982ea4592afc5109160c63d728f1fdaa8373,PMC,Comparative Research for the Healthcare Budget and Burden of Disease in Perspective Resource Allocation,http://dx.doi.org/10.3346/jkms.2019.34.e81,PMC6434158,30923490,CC BY-NC,"BACKGROUND: Burden of disease can be used to prioritize the healthcare budget allocation. We analyzed the research and development (R&D) budget of the Ministry of Health and Welfare (MOHW) in 2018 and compared the results with those of the 2015 Korean National Burden of Disease (KNBD) study. METHODS: The 2018 MOHW R&D Project integrated implementation plan was used to analyze the R&D budget of the MOHW. The budget was allocated according to the KNBD disease group and according to the budget lines. The allocated budget was compared with the economic burden and the disability adjusted life years (DALYs) in 2015. Also, for budget targets for risk factors, DALYs of attributable risk factors were compared with corresponding budgets. RESULTS: In 2018, the MOHW major R&D budget of USD 435.1 million accounted for 3% of the total government budget. Within the disease specific R&D budget, 35.9% was allocated to communicable disease groups, 64.1% to non-communicable diseases, and 0% to injury and violence. Among level 2 disease groups, neoplasm was ranked first. Among risk factors, climate change and behavioral risk were targeted for R&D. CONCLUSIONS: It would be difficult to say that current R&D allocations focus to minimize the burden of disease. A mismatch was observed between the R&D budget and the burden of disease in terms of economic burden and DALYs. There was a similar finding for risk factors R&D. A novel approach for allocating government R&D funding that is based on the goal of minimizing the disease burden in the Korean population should be considered.",2019 Mar 7,"['Park, So-Youn', 'Yoon, Seok-Jun', 'Park, Hyesook', 'Jo, Min-Woo', 'Oh, In-Hwan']",J Korean Med Sci,,,True
7037460cc980744603573744bf370ee8f49a4ffe,PMC,Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis,http://dx.doi.org/10.1177/1098612X19825701,PMC6435921,30755068,CC BY-NC,"OBJECTIVES: The aim of this study was to determine the safety and efficacy of the nucleoside analog GS-441524 for cats suffering from various forms of naturally acquired feline infectious peritonitis (FIP). METHODS: Cats ranged from 3.4–73 months of age (mean 13.6 months); 26 had effusive or dry-to-effusive FIP and five had non-effusive disease. Cats with severe neurological and ocular FIP were not recruited. The group was started on GS-441524 at a dosage of 2.0 mg/kg SC q24h for at least 12 weeks and increased when indicated to 4.0 mg/kg SC q24h. RESULTS: Four of the 31 cats that presented with severe disease died or were euthanized within 2–5 days and a fifth cat after 26 days. The 26 remaining cats completed the planned 12 weeks or more of treatment. Eighteen of these 26 cats remain healthy at the time of publication (OnlineFirst, February 2019) after one round of treatment, while eight others suffered disease relapses within 3–84 days. Six of the relapses were non-neurological and two neurological. Three of the eight relapsing cats were treated again at the same dosage, while five cats had the dosage increased from 2.0 to 4.0 mg/kg q24h. The five cats treated a second time at the higher dosage, including one with neurological disease, responded well and also remain healthy at the time of publication. However, one of the three cats re-treated at the original lower dosage relapsed with neurological disease and was euthanized, while the two remaining cats responded favorably but relapsed a second time. These two cats were successfully treated a third time at the higher dosage, producing 25 long-time survivors. One of the 25 successfully treated cats was subsequently euthanized due to presumably unrelated heart disease, while 24 remain healthy. CONCLUSIONS AND RELEVANCE: GS-441524 was shown to be a safe and effective treatment for FIP. The optimum dosage was found to be 4.0 mg/kg SC q24h for at least 12 weeks.",2019 Apr 13,"['Pedersen, Niels C', 'Perron, Michel', 'Bannasch, Michael', 'Montgomery, Elizabeth', 'Murakami, Eisuke', 'Liepnieks, Molly', 'Liu, Hongwei']",J Feline Med Surg,,,True
7a53295a349dc3079dc20b769ba956e07d7f2496,PMC,First report of Enterocytozoon bieneusi and Cryptosporidium spp. in peafowl (Pavo cristatus) in China,http://dx.doi.org/10.1016/j.ijppaw.2019.03.014,PMC6438908,30976510,CC BY-NC-ND,"Enterocytozoon bieneusi and Cryptosporidium spp. are important pathogens causing diarrhea in humans and animals. However, few studies have been conducted on the infection of E. bieneusi and Cryptosporidium spp. in peafowl up to now. The purpose of the present study was to determine the prevalence and the involved genotypes of Cryptosporidium spp. and E. bieneusi in peafowl in Beijing and Jiangxi Province, China. In total, 258 peafowl fecal samples were collected. Overall, both Cryptosporidium spp. and E. bieneusi had the same prevalence, i.e. 6.59% (17/258). Higher infection rates of E. bieneusi and Cryptosporidium spp. were found in the adolescent peafowl. The prevalence of E. bieneusi in Beijing and Jiangxi Province was 5.23% and 8.57% respectively. For Cryptosporidium spp., the prevalence was 4.58% and 9.52% in Beijing and Jiangxi Province, respectively. Three zoonotic genotypes of E. bieneusi were confirmed, including two known genotypes, genotype Peru 6 and D, and one novel genotype, JXP1. Two avian specific species/genotypes of Cryptosporidium, Avian genotype Ⅲ and Goose genotype Ⅰ, were identified. To our knowledge, this is the first report of E. bieneusi and Cryptosporidium spp. occurrence in peafowl in China. The findings suggest that peafowl could be reservoirs of E. bieneusi and Cryptosporidium spp. which could be potentially transmitted to humans and other animals, and the present survey have implications for controlling E. bieneusi and Cryptosporidium spp. infection in peafowl.",2019 Mar 23,"['Feng, Sheng-Yong', 'Chang, Han', 'Luo, Jing', 'Huang, Jing-Jing', 'He, Hong-Xuan']",Int J Parasitol Parasites Wildl,,,False
2c602e06cc01660017717021bf172b821491700e,PMC,Plant-derived antiviral drugs as novel hepatitis B virus inhibitors: Cell culture and molecular docking study,http://dx.doi.org/10.1016/j.jsps.2018.12.008,PMC6439212,30976183,CC BY-NC-ND,"Despite high anti-HBV efficacies, while the nucleoside analogs (e.g., lamivudine) lead to the emergence of drug-resistance, interferons (e.g., IFN-α causes adverse side-effects. Comparatively, various natural or plant products have shown similar or even better efficacy. Hence, new antiviral strategies must focus not only on synthetic molecules but also on potential natural compounds. In this report, we have combined the in vitro cell culture and in silico molecular docking methods to assess the novel anti-HBV activity and delineate the inhibitory mechanism of selected plant-derived pure compounds of different classes. Of the tested (2.5-50 μg/ml) twelve non-cytotoxic compounds, ten (10 μg/ml) were found to maximally inhibit HBsAg production at day 5. Compared to quercetin (73%), baccatin III (71%), psoralen (67%), embelin (65%), menisdaurin (64%) and azadirachtin (62%) that showed high inhibition of HBeAg synthesis, lupeol (52%), rutin (47%), β-sitosterol (43%) and hesperidin (41%) had moderate efficacies against HBV replication. Further assessment of quercetin in combination with the highly active compounds, enhanced its anti-HBV activity up to 10%. Being the most important drug target, a 3-D structure of HBV polymerase (Pol/RT) was modeled and docked with the active compounds, including lamivudine as standard. Docking of lamivudine indicated strong interaction with the modeled HBV Pol active-site residues that formed stable complex (∆G = −5.2 kcal/mol). Similarly, all the docked antiviral compounds formed very stable complexes with HBV Pol (∆G = −6.1 to −9.3 kcal/mol). Taken together, our data suggest the anti-HBV potential of the tested natural compounds as novel viral Pol/RT inhibitors.",2019 Mar 26,"['Parvez, Mohammad K.', 'Tabish Rehman, Md.', 'Alam, Perwez', 'Al-Dosari, Mohammed S.', 'Alqasoumi, Saleh I.', 'Alajmi, Mohammed F.']",Saudi Pharm J,,,False
c95aea18951cb2b0ba90fe898b92b09ac419c5b9,PMC,Type I interferon protects neurons from prions in in vivo models,http://dx.doi.org/10.1093/brain/awz016,PMC6439327,30753318,CC BY-NC,"Infectious prions comprising abnormal prion protein, which is produced by structural conversion of normal prion protein, are responsible for transmissible spongiform encephalopathies including Creutzfeldt-Jakob disease in humans. Prions are infectious agents that do not possess a genome and the pathogenic protein was not thought to evoke any immune response. Although we previously reported that interferon regulatory factor 3 (IRF3) was likely to be involved in the pathogenesis of prion diseases, suggesting the protective role of host innate immune responses mediated by IRF3 signalling, this remained to be clarified. Here, we investigated the reciprocal interactions of type I interferon evoked by IRF3 activation and prion infection and found that infecting prions cause the suppression of endogenous interferon expression. Conversely, treatment with recombinant interferons in an ex vivo model was able to inhibit prion infection. In addition, cells and mice deficient in type I interferon receptor (subunit interferon alpha/beta receptor 1), exhibited higher susceptibility to 22L-prion infection. Moreover, in in vivo and ex vivo prion-infected models, treatment with RO8191, a selective type I interferon receptor agonist, inhibited prion invasion and prolonged the survival period of infected mice. Taken together, these data indicated that the interferon signalling interferes with prion propagation and some interferon-stimulated genes might play protective roles in the brain. These findings may allow for the development of new strategies to combat fatal diseases.",2019 Apr 7,"['Ishibashi, Daisuke', 'Homma, Takujiro', 'Nakagaki, Takehiro', 'Fuse, Takayuki', 'Sano, Kazunori', 'Satoh, Katsuya', 'Mori, Tsuyoshi', 'Atarashi, Ryuichiro', 'Nishida, Noriyuki']",Brain,,,True
ad59a9758295c7788db943e2a737915fd07c2739,PMC,Type I interferon protects neurons from prions in in vivo models,http://dx.doi.org/10.1093/brain/awz016,PMC6439327,30753318,CC BY-NC,"Infectious prions comprising abnormal prion protein, which is produced by structural conversion of normal prion protein, are responsible for transmissible spongiform encephalopathies including Creutzfeldt-Jakob disease in humans. Prions are infectious agents that do not possess a genome and the pathogenic protein was not thought to evoke any immune response. Although we previously reported that interferon regulatory factor 3 (IRF3) was likely to be involved in the pathogenesis of prion diseases, suggesting the protective role of host innate immune responses mediated by IRF3 signalling, this remained to be clarified. Here, we investigated the reciprocal interactions of type I interferon evoked by IRF3 activation and prion infection and found that infecting prions cause the suppression of endogenous interferon expression. Conversely, treatment with recombinant interferons in an ex vivo model was able to inhibit prion infection. In addition, cells and mice deficient in type I interferon receptor (subunit interferon alpha/beta receptor 1), exhibited higher susceptibility to 22L-prion infection. Moreover, in in vivo and ex vivo prion-infected models, treatment with RO8191, a selective type I interferon receptor agonist, inhibited prion invasion and prolonged the survival period of infected mice. Taken together, these data indicated that the interferon signalling interferes with prion propagation and some interferon-stimulated genes might play protective roles in the brain. These findings may allow for the development of new strategies to combat fatal diseases.",2019 Apr 7,"['Ishibashi, Daisuke', 'Homma, Takujiro', 'Nakagaki, Takehiro', 'Fuse, Takayuki', 'Sano, Kazunori', 'Satoh, Katsuya', 'Mori, Tsuyoshi', 'Atarashi, Ryuichiro', 'Nishida, Noriyuki']",Brain,,,False
0e2a8d77e70775a89a1be92c4f2c5d86f5caece2,PMC,Recreational ‘mud fever’: Leptospira interrogans induced diffuse alveolar hemorrhage and severe acute respiratory distress syndrome in a U.S. Navy seaman following ‘mud-run’ in Hawaii,http://dx.doi.org/10.1016/j.idcr.2019.e00529,PMC6441746,30976519,CC BY-NC-ND,"A 23-year-old man with a viral-like prodrome developed sudden severe dyspnea and was found to have renal failure, anemia, shock, and diffuse alveolar hemorrhage with acute respiratory distress syndrome, requiring emergent endotracheal intubation and extracorporeal membrane oxygenation (ECMO). Travel and exposure history from peripheral sources revealed that the patient had participated in a ‘mud-run’ in Hawaii two weeks prior to symptom onset. The patient was subsequently diagnosed with leptospirosis and treated with ceftriaxone and doxycycline. He was discharged on hospital day 13 with full recovery. Leptospirosis is associated with exposure to water, soil, or other matter contaminated with urine of carrier animals. It has been associated with a multitude of activities over time; most recently recreational water-based activities including ‘mud-runs’ in endemic areas have been added to the list of routes of exposure. This case underscores the importance of obtaining a thorough epidemiological exposure and travel history and being aware of areas of endemicity for life-threatening infections. Additionally, to our knowledge this is the second case of a patient in the United States treated with ECMO for leptospirosis induced pulmonary hemorrhage.",2019 Mar 23,"['Schmalzle, Sarah A', 'Tabatabai, Ali', 'Mazzeffi, Michael', 'Matta, Ann', 'Hollis, Allison', 'Zubrow, Marc', 'Rajagopal, Keshava', 'Thom, Kerri', 'Scalea, Thomas']",IDCases,,,False
18cdd1a1d97483f2cb8a1586b2d4858dab46efa2,PMC,Evolutionary relationship analysis of Middle East respiratory syndrome coronavirus 4a and 4b protein coding sequences,http://dx.doi.org/10.4142/jvs.2019.20.e1,PMC6441811,30944524,CC BY-NC,"The 4a and 4b proteins of the Middle East respiratory syndrome coronavirus (MERS-CoV) have been described for their antagonism on host innate immunity. However, unlike clustering patterns of the complete gene sequences of human and camel MERS-CoVs, the 4a and 4b protein coding regions did not constitute species-specific phylogenetic groups. Moreover, given the estimated evolutionary rates of the complete, 4a, and 4b gene sequences, the 4a and 4b proteins might be less affected by species-specific innate immune pressures. These results suggest that the 4a and 4b proteins of MERS-CoV may function against host innate immunity in a manner independent of host species and/or evolutionary clustering patterns.",2019 Mar 19,"['Kim, Jin Il', 'Park, Sehee', 'Bae, Joon-Yong', 'Park, Man-Seong']",J Vet Sci,,,True
8ae4a09bc3001554f0639e2b139ee2565fe1aad3,PMC,Oxidized LDL upregulates macrophage DPP4 expression via TLR4/TRIF/CD36 pathways,http://dx.doi.org/10.1016/j.ebiom.2019.01.065,PMC6441950,30738832,CC BY-NC-ND,"BACKGROUND: We and others have shown that dipeptidyl peptidase-IV (DPP4) expression is increased in obesity/atherosclerosis and is positively correlated with atherosclerotic burden. However, the mechanism by which DPP4 expression is regulated in obesity remains unclear. In this study, we investigated the pathways regulating the expression of DPP4 on macrophages. METHODS: Flowsight® Imaging Flow Cytometry was employed for the detection of DPP4 and immunophenotyping. DPP4 enzymatic activity was measured by a DPPIV-Glo™ Protease Assay kit. FINDINGS: Human monocytes expressed a moderate level of membrane-bound DPP4. Obese patients with body mass index (BMI) ≥ 30 had a higher level of monocyte DPP4 expression, in parallel with higher levels of HOMA-IR, blood glucose, triglycerides, and non-HDL cholesterol, compared to those in the non-obese (BMI < 30) patients. Oxidized low-density lipoprotein (oxLDL), but not native LDL, up-regulated DPP4 expression on macrophages with a preferential increase in CD36(+) cells. OxLDL mediated DPP4 up-regulation was considerably diminished by Toll-like receptor-4 (TLR4) knockdown and CD36 deficiency. TRIF deficiency, but not MyD88 deficiency, attenuated oxLDL-induced DPP4 increase. INTERPRETATION: Our study suggests a key role for oxLDL and downstream CD36/TLR4/TRIF in regulating DPP4 expression. Increased DPP4 in response to oxidized lipids may represent an integrated mechanism linking post-prandial glucose metabolism to lipoprotein abnormality-potentiated atherosclerosis.",2019 Feb 7,"['Rao, Xiaoquan', 'Zhao, Shi', 'Braunstein, Zachary', 'Mao, Hong', 'Razavi, Michael', 'Duan, Lihua', 'Wei, Yingying', 'Toomey, Amelia C.', 'Rajagopalan, Sanjay', 'Zhong, Jixin']",EBioMedicine,,,False
6e068d9060b30bf3ea11b0b6cbabf6ebcdd58a93,PMC,Oxidized LDL upregulates macrophage DPP4 expression via TLR4/TRIF/CD36 pathways,http://dx.doi.org/10.1016/j.ebiom.2019.01.065,PMC6441950,30738832,CC BY-NC-ND,"BACKGROUND: We and others have shown that dipeptidyl peptidase-IV (DPP4) expression is increased in obesity/atherosclerosis and is positively correlated with atherosclerotic burden. However, the mechanism by which DPP4 expression is regulated in obesity remains unclear. In this study, we investigated the pathways regulating the expression of DPP4 on macrophages. METHODS: Flowsight® Imaging Flow Cytometry was employed for the detection of DPP4 and immunophenotyping. DPP4 enzymatic activity was measured by a DPPIV-Glo™ Protease Assay kit. FINDINGS: Human monocytes expressed a moderate level of membrane-bound DPP4. Obese patients with body mass index (BMI) ≥ 30 had a higher level of monocyte DPP4 expression, in parallel with higher levels of HOMA-IR, blood glucose, triglycerides, and non-HDL cholesterol, compared to those in the non-obese (BMI < 30) patients. Oxidized low-density lipoprotein (oxLDL), but not native LDL, up-regulated DPP4 expression on macrophages with a preferential increase in CD36(+) cells. OxLDL mediated DPP4 up-regulation was considerably diminished by Toll-like receptor-4 (TLR4) knockdown and CD36 deficiency. TRIF deficiency, but not MyD88 deficiency, attenuated oxLDL-induced DPP4 increase. INTERPRETATION: Our study suggests a key role for oxLDL and downstream CD36/TLR4/TRIF in regulating DPP4 expression. Increased DPP4 in response to oxidized lipids may represent an integrated mechanism linking post-prandial glucose metabolism to lipoprotein abnormality-potentiated atherosclerosis.",2019 Feb 7,"['Rao, Xiaoquan', 'Zhao, Shi', 'Braunstein, Zachary', 'Mao, Hong', 'Razavi, Michael', 'Duan, Lihua', 'Wei, Yingying', 'Toomey, Amelia C.', 'Rajagopalan, Sanjay', 'Zhong, Jixin']",EBioMedicine,,,False
8d612e0c4433db428f3e06657888d5296a43b653,PMC,Geographical disparities in emergency department presentations for acute respiratory infections and risk factors for presenting: a population-based cohort study of Western Australian children,http://dx.doi.org/10.1136/bmjopen-2018-025360,PMC6443078,30804033,CC BY-NC,"INTRODUCTION: Studies examining acute respiratory infections (ARIs) in emergency department (EDs), particularly in rural and remote areas, are rare. This study aimed to examine the burden of ARIs among Aboriginal and non-Aboriginal children presenting to Western Australian (WA) EDs from 2002 to 2012. METHOD: Using a retrospective population-based cohort study linking ED records to birth and perinatal records, we examined presentation rates for metropolitan, rural and remote Aboriginal and non-Aboriginal children from 469 589 births. We used ED diagnosis information to categorise presentations into ARI groups and calculated age-specific rates. Negative binomial regression was used to investigate association between risk factors and frequency of ARI presentation. RESULTS: Overall, 26% of presentations were for ARIs. For Aboriginal children, the highest rates were for those aged <12 months in the Great Southern (1233 per 1000 child-years) and Pilbara regions (1088 per 1000 child-years). Rates for non-Aboriginal children were highest in children <12 months in the Southwest and Kimberley (400 and 375 per 1000 child-years, respectively). Presentation rates for ARI in children from rural and remote WA significantly increased over time in all age groups <5 years. Risk factors for children presenting to ED with ARI were: male, prematurity, caesarean delivery and residence in the Kimberley region and lower socio-economic areas. CONCLUSION: One in four ED presentations in WA children are for ARIs, representing a significant out-of-hospital burden with some evidence of geographical disparity. Planned linkages with hospital discharge and laboratory detection data will aid in assessing the sensitivity and specificity of ARI diagnoses in ED.",2019 Feb 24,"['Barnes, Rosanne', 'Blyth, Christopher C', 'de Klerk, Nicholas', 'Lee, Wei Hao', 'Borland, Meredith L', 'Richmond, Peter', 'Lim, Faye J', 'Fathima, Parveen', 'Moore, Hannah C']",BMJ Open,,,True
8d732d6fc180c5be5a7c49cd8d8cf49332d24b39,PMC,Geographical disparities in emergency department presentations for acute respiratory infections and risk factors for presenting: a population-based cohort study of Western Australian children,http://dx.doi.org/10.1136/bmjopen-2018-025360,PMC6443078,30804033,CC BY-NC,"INTRODUCTION: Studies examining acute respiratory infections (ARIs) in emergency department (EDs), particularly in rural and remote areas, are rare. This study aimed to examine the burden of ARIs among Aboriginal and non-Aboriginal children presenting to Western Australian (WA) EDs from 2002 to 2012. METHOD: Using a retrospective population-based cohort study linking ED records to birth and perinatal records, we examined presentation rates for metropolitan, rural and remote Aboriginal and non-Aboriginal children from 469 589 births. We used ED diagnosis information to categorise presentations into ARI groups and calculated age-specific rates. Negative binomial regression was used to investigate association between risk factors and frequency of ARI presentation. RESULTS: Overall, 26% of presentations were for ARIs. For Aboriginal children, the highest rates were for those aged <12 months in the Great Southern (1233 per 1000 child-years) and Pilbara regions (1088 per 1000 child-years). Rates for non-Aboriginal children were highest in children <12 months in the Southwest and Kimberley (400 and 375 per 1000 child-years, respectively). Presentation rates for ARI in children from rural and remote WA significantly increased over time in all age groups <5 years. Risk factors for children presenting to ED with ARI were: male, prematurity, caesarean delivery and residence in the Kimberley region and lower socio-economic areas. CONCLUSION: One in four ED presentations in WA children are for ARIs, representing a significant out-of-hospital burden with some evidence of geographical disparity. Planned linkages with hospital discharge and laboratory detection data will aid in assessing the sensitivity and specificity of ARI diagnoses in ED.",2019 Feb 24,"['Barnes, Rosanne', 'Blyth, Christopher C', 'de Klerk, Nicholas', 'Lee, Wei Hao', 'Borland, Meredith L', 'Richmond, Peter', 'Lim, Faye J', 'Fathima, Parveen', 'Moore, Hannah C']",BMJ Open,,,True
4fab9d6fcfd7daca9ed2e0f89c2433955d34e553,PMC,Geographical disparities in emergency department presentations for acute respiratory infections and risk factors for presenting: a population-based cohort study of Western Australian children,http://dx.doi.org/10.1136/bmjopen-2018-025360,PMC6443078,30804033,CC BY-NC,"INTRODUCTION: Studies examining acute respiratory infections (ARIs) in emergency department (EDs), particularly in rural and remote areas, are rare. This study aimed to examine the burden of ARIs among Aboriginal and non-Aboriginal children presenting to Western Australian (WA) EDs from 2002 to 2012. METHOD: Using a retrospective population-based cohort study linking ED records to birth and perinatal records, we examined presentation rates for metropolitan, rural and remote Aboriginal and non-Aboriginal children from 469 589 births. We used ED diagnosis information to categorise presentations into ARI groups and calculated age-specific rates. Negative binomial regression was used to investigate association between risk factors and frequency of ARI presentation. RESULTS: Overall, 26% of presentations were for ARIs. For Aboriginal children, the highest rates were for those aged <12 months in the Great Southern (1233 per 1000 child-years) and Pilbara regions (1088 per 1000 child-years). Rates for non-Aboriginal children were highest in children <12 months in the Southwest and Kimberley (400 and 375 per 1000 child-years, respectively). Presentation rates for ARI in children from rural and remote WA significantly increased over time in all age groups <5 years. Risk factors for children presenting to ED with ARI were: male, prematurity, caesarean delivery and residence in the Kimberley region and lower socio-economic areas. CONCLUSION: One in four ED presentations in WA children are for ARIs, representing a significant out-of-hospital burden with some evidence of geographical disparity. Planned linkages with hospital discharge and laboratory detection data will aid in assessing the sensitivity and specificity of ARI diagnoses in ED.",2019 Feb 24,"['Barnes, Rosanne', 'Blyth, Christopher C', 'de Klerk, Nicholas', 'Lee, Wei Hao', 'Borland, Meredith L', 'Richmond, Peter', 'Lim, Faye J', 'Fathima, Parveen', 'Moore, Hannah C']",BMJ Open,,,True
7ae3ad07fe12d216b26ff679b77df0e1df054ecf,PMC,Geographical disparities in emergency department presentations for acute respiratory infections and risk factors for presenting: a population-based cohort study of Western Australian children,http://dx.doi.org/10.1136/bmjopen-2018-025360,PMC6443078,30804033,CC BY-NC,"INTRODUCTION: Studies examining acute respiratory infections (ARIs) in emergency department (EDs), particularly in rural and remote areas, are rare. This study aimed to examine the burden of ARIs among Aboriginal and non-Aboriginal children presenting to Western Australian (WA) EDs from 2002 to 2012. METHOD: Using a retrospective population-based cohort study linking ED records to birth and perinatal records, we examined presentation rates for metropolitan, rural and remote Aboriginal and non-Aboriginal children from 469 589 births. We used ED diagnosis information to categorise presentations into ARI groups and calculated age-specific rates. Negative binomial regression was used to investigate association between risk factors and frequency of ARI presentation. RESULTS: Overall, 26% of presentations were for ARIs. For Aboriginal children, the highest rates were for those aged <12 months in the Great Southern (1233 per 1000 child-years) and Pilbara regions (1088 per 1000 child-years). Rates for non-Aboriginal children were highest in children <12 months in the Southwest and Kimberley (400 and 375 per 1000 child-years, respectively). Presentation rates for ARI in children from rural and remote WA significantly increased over time in all age groups <5 years. Risk factors for children presenting to ED with ARI were: male, prematurity, caesarean delivery and residence in the Kimberley region and lower socio-economic areas. CONCLUSION: One in four ED presentations in WA children are for ARIs, representing a significant out-of-hospital burden with some evidence of geographical disparity. Planned linkages with hospital discharge and laboratory detection data will aid in assessing the sensitivity and specificity of ARI diagnoses in ED.",2019 Feb 24,"['Barnes, Rosanne', 'Blyth, Christopher C', 'de Klerk, Nicholas', 'Lee, Wei Hao', 'Borland, Meredith L', 'Richmond, Peter', 'Lim, Faye J', 'Fathima, Parveen', 'Moore, Hannah C']",BMJ Open,,,False
d912056b2587126dc6cdbbebc8572c9b56a65691,PMC,Geographical disparities in emergency department presentations for acute respiratory infections and risk factors for presenting: a population-based cohort study of Western Australian children,http://dx.doi.org/10.1136/bmjopen-2018-025360,PMC6443078,30804033,CC BY-NC,"INTRODUCTION: Studies examining acute respiratory infections (ARIs) in emergency department (EDs), particularly in rural and remote areas, are rare. This study aimed to examine the burden of ARIs among Aboriginal and non-Aboriginal children presenting to Western Australian (WA) EDs from 2002 to 2012. METHOD: Using a retrospective population-based cohort study linking ED records to birth and perinatal records, we examined presentation rates for metropolitan, rural and remote Aboriginal and non-Aboriginal children from 469 589 births. We used ED diagnosis information to categorise presentations into ARI groups and calculated age-specific rates. Negative binomial regression was used to investigate association between risk factors and frequency of ARI presentation. RESULTS: Overall, 26% of presentations were for ARIs. For Aboriginal children, the highest rates were for those aged <12 months in the Great Southern (1233 per 1000 child-years) and Pilbara regions (1088 per 1000 child-years). Rates for non-Aboriginal children were highest in children <12 months in the Southwest and Kimberley (400 and 375 per 1000 child-years, respectively). Presentation rates for ARI in children from rural and remote WA significantly increased over time in all age groups <5 years. Risk factors for children presenting to ED with ARI were: male, prematurity, caesarean delivery and residence in the Kimberley region and lower socio-economic areas. CONCLUSION: One in four ED presentations in WA children are for ARIs, representing a significant out-of-hospital burden with some evidence of geographical disparity. Planned linkages with hospital discharge and laboratory detection data will aid in assessing the sensitivity and specificity of ARI diagnoses in ED.",2019 Feb 24,"['Barnes, Rosanne', 'Blyth, Christopher C', 'de Klerk, Nicholas', 'Lee, Wei Hao', 'Borland, Meredith L', 'Richmond, Peter', 'Lim, Faye J', 'Fathima, Parveen', 'Moore, Hannah C']",BMJ Open,,,False
e8f1edfb8249017f774ccc05dea2ab17be144313,PMC,OAS1 and OAS3 negatively regulate the expression of chemokines and interferon-responsive genes in human macrophages,http://dx.doi.org/10.5483/BMBRep.2019.52.2.129,PMC6443328,30078389,CC BY-NC,"Upon viral infection, the 2′, 5′-oligoadenylate synthetase (OAS)-ribonuclease L (RNaseL) system works to cleave viral RNA, thereby blocking viral replication. However, it is unclear whether OAS proteins have a role in regulating gene expression. Here, we show that OAS1 and OAS3 act as negative regulators of the expression of chemokines and interferon-responsive genes in human macrophages. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (Cas9) technology was used to engineer human myeloid cell lines in which the OAS1 or OAS3 gene was deleted. Neither OAS1 nor OAS3 was exclusively responsible for the degradation of rRNA in macrophages stimulated with poly(I:C), a synthetic surrogate for viral double-stranded (ds)RNA. An mRNA sequencing analysis revealed that genes related to type I interferon signaling and chemokine activity were increased in OAS1(−/−) and OAS3(−/−) macrophages treated with intracellular poly(I:C). Indeed, retinoic-acid-inducible gene (RIG)-I- and interferon-induced helicase C domain-containing protein (IFIH1 or MDA5)-mediated induction of chemokines and interferon-stimulated genes was regulated by OAS3, but Toll-like receptor 3 (TLR3)- and TLR4-mediated induction of those genes was modulated by OAS1 in macrophages. However, stimulation of these cells with type I interferons had no effect on OAS1- or OAS3-mediated chemokine secretion. These data suggest that OAS1 and OAS3 negatively regulate the expression of chemokines and interferon-responsive genes in human macrophages.",2019 Feb 28,"['Lee, Wook-Bin', 'Choi, Won Young', 'Lee, Dong-Hyun', 'Shim, Hyeran', 'Kim-Ha, Jeongsil', 'Kim, Young-Joon']",BMB Rep,,,True
7b1e5a1aa29a9959214b1cb462d689d6a1a8abb2,PMC,OAS1 and OAS3 negatively regulate the expression of chemokines and interferon-responsive genes in human macrophages,http://dx.doi.org/10.5483/BMBRep.2019.52.2.129,PMC6443328,30078389,CC BY-NC,"Upon viral infection, the 2′, 5′-oligoadenylate synthetase (OAS)-ribonuclease L (RNaseL) system works to cleave viral RNA, thereby blocking viral replication. However, it is unclear whether OAS proteins have a role in regulating gene expression. Here, we show that OAS1 and OAS3 act as negative regulators of the expression of chemokines and interferon-responsive genes in human macrophages. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (Cas9) technology was used to engineer human myeloid cell lines in which the OAS1 or OAS3 gene was deleted. Neither OAS1 nor OAS3 was exclusively responsible for the degradation of rRNA in macrophages stimulated with poly(I:C), a synthetic surrogate for viral double-stranded (ds)RNA. An mRNA sequencing analysis revealed that genes related to type I interferon signaling and chemokine activity were increased in OAS1(−/−) and OAS3(−/−) macrophages treated with intracellular poly(I:C). Indeed, retinoic-acid-inducible gene (RIG)-I- and interferon-induced helicase C domain-containing protein (IFIH1 or MDA5)-mediated induction of chemokines and interferon-stimulated genes was regulated by OAS3, but Toll-like receptor 3 (TLR3)- and TLR4-mediated induction of those genes was modulated by OAS1 in macrophages. However, stimulation of these cells with type I interferons had no effect on OAS1- or OAS3-mediated chemokine secretion. These data suggest that OAS1 and OAS3 negatively regulate the expression of chemokines and interferon-responsive genes in human macrophages.",2019 Feb 28,"['Lee, Wook-Bin', 'Choi, Won Young', 'Lee, Dong-Hyun', 'Shim, Hyeran', 'Kim-Ha, Jeongsil', 'Kim, Young-Joon']",BMB Rep,,,False
84388602b1574ebc0b2cdffa1d5ea4ec5ba22b40,PMC,Trends of participation of post-graduate year training program for dentists in Taiwan dental training institutions from 2010 to 2018,http://dx.doi.org/10.1016/j.jds.2018.11.001,PMC6445971,30988879,CC BY-NC-ND,"BACKGROUND/PURPOSE: The licensed dentists in Taiwan should join the post-graduate year training program for dentists (PGYD) since 2010. This study aimed to analyze the project types and the geographical distribution of the PGYD training institutions in Taiwan from 2010 to 2018. MATERIALS AND METHODS: From 2010 to 2018, 735 hospitals and clinics participated in four types of PGYD project including hospital as the single training institution (project A), clinic as the single training institution (project B), hospital as the main training institution in the joint training group (project C), and clinic as the main training institution in the joint training group (project D). The project types and the geographical distribution of the training institutions were analyzed. RESULTS: The 735 PGYD training projects were proposed by the 735 dental institutions. The project number grew from 119 in 2010 to 195 in 2018. The most common project type was project B (307, 41.8%), followed by the project A (249, 33.9%), the project D (101, 13.7%), and the project C (78, 10.6%). Geographically, these 735 main training institutions were located most commonly in northern region of Taiwan (379, 51.6%), followed by the central region of Taiwan (171, 23.3%), southern region of Taiwan (156, 21.2%), and eastern region of Taiwan (29, 3.9%). CONCLUSION: Hospital or clinic as the single training institution is the two most common PGYD project types in Taiwan from 2010 to 2018. These single or main dental training institutions are mainly located in the northern, central, and southern regions of Taiwan.",2019 Mar 15,"['Cheng, Feng-Chou', 'Chiang, Chun-Pin', 'Lin, Tzu-Chiang', 'Chang, Wen-Chiung', 'Hsiang-Hua Lai, Eddie', 'Chang, Yung-Ta']",J Dent Sci,,,False
85f4ff3ff33bcc47e9826ee3bd468626fba5870d,PMC,A case report of a ruptured subclavian artery aneurysm presenting to the emergency department,http://dx.doi.org/10.1002/ccr3.2098,PMC6452447,30997088,CC BY-NC,"Subclavian artery aneurysms are uncommon and present a diagnostic dilemma. Our patient attended with life‐threatening rupture, requiring prompt management. However, lack of on‐site facilities and specialist input posed a logistical challenge. The patient was stable enough to allow an urgent transfer to a specialist unit for successful endovascular repair.",2019 Mar 12,"['Ramtoola, Mohammad Tariq', 'Bhatti, Mubashir', 'Shetty, Ritesh']",Clin Case Rep,,,True
c1a29945f51707d279560855da521ea878989333,PMC,A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike,http://dx.doi.org/10.1126/sciadv.aav4580,PMC6457931,30989115,CC BY-NC,"Continuously emerging highly pathogenic human coronaviruses (HCoVs) remain a major threat to human health, as illustrated in past SARS-CoV and MERS-CoV outbreaks. The development of a drug with broad-spectrum HCoV inhibitory activity would address this urgent unmet medical need. Although previous studies have suggested that the HR1 of HCoV spike (S) protein is an important target site for inhibition against specific HCoVs, whether this conserved region could serve as a target for the development of broad-spectrum pan-CoV inhibitor remains controversial. Here, we found that peptide OC43-HR2P, derived from the HR2 domain of HCoV-OC43, exhibited broad fusion inhibitory activity against multiple HCoVs. EK1, the optimized form of OC43-HR2P, showed substantially improved pan-CoV fusion inhibitory activity and pharmaceutical properties. Crystal structures indicated that EK1 can form a stable six-helix bundle structure with both short α-HCoV and long β-HCoV HR1s, further supporting the role of HR1 region as a viable pan-CoV target site.",2019 Apr 10,"['Xia, Shuai', 'Yan, Lei', 'Xu, Wei', 'Agrawal, Anurodh Shankar', 'Algaissi, Abdullah', 'Tseng, Chien-Te K.', 'Wang, Qian', 'Du, Lanying', 'Tan, Wenjie', 'Wilson, Ian A.', 'Jiang, Shibo', 'Yang, Bei', 'Lu, Lu']",Sci Adv,,,True
c11a0262b97aadec1035217c46b546a45f844c35,PMC,A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike,http://dx.doi.org/10.1126/sciadv.aav4580,PMC6457931,30989115,CC BY-NC,"Continuously emerging highly pathogenic human coronaviruses (HCoVs) remain a major threat to human health, as illustrated in past SARS-CoV and MERS-CoV outbreaks. The development of a drug with broad-spectrum HCoV inhibitory activity would address this urgent unmet medical need. Although previous studies have suggested that the HR1 of HCoV spike (S) protein is an important target site for inhibition against specific HCoVs, whether this conserved region could serve as a target for the development of broad-spectrum pan-CoV inhibitor remains controversial. Here, we found that peptide OC43-HR2P, derived from the HR2 domain of HCoV-OC43, exhibited broad fusion inhibitory activity against multiple HCoVs. EK1, the optimized form of OC43-HR2P, showed substantially improved pan-CoV fusion inhibitory activity and pharmaceutical properties. Crystal structures indicated that EK1 can form a stable six-helix bundle structure with both short α-HCoV and long β-HCoV HR1s, further supporting the role of HR1 region as a viable pan-CoV target site.",2019 Apr 10,"['Xia, Shuai', 'Yan, Lei', 'Xu, Wei', 'Agrawal, Anurodh Shankar', 'Algaissi, Abdullah', 'Tseng, Chien-Te K.', 'Wang, Qian', 'Du, Lanying', 'Tan, Wenjie', 'Wilson, Ian A.', 'Jiang, Shibo', 'Yang, Bei', 'Lu, Lu']",Sci Adv,,,False
5db655de0fdc5e28e3fc13f279b5068c30e9cdc2,PMC,"Coptidis Rhizoma: a comprehensive review of its traditional uses, botany, phytochemistry, pharmacology and toxicology",http://dx.doi.org/10.1080/13880209.2019.1577466,PMC6461078,30963783,CC BY-NC,"Context: Coptidis rhizome (CR), also known as Huanglian in Chinese, is the rhizome of Coptis chinensis Franch., C. deltoidea C.Y. Cheng et Hsiao, or C. teeta Wall (Ranunculaceae). It has been widely used to treat bacillary dysentery, diabetes, pertussis, sore throat, aphtha, and eczema in China. Objectives: The present paper reviews the latest advances of CR, focusing on the botany, phytochemistry, traditional usages, pharmacokinetics, pharmacology and toxicology of CR and its future perspectives. Methods: Studies from 1985 to 2018 were reviewed from books; PhD. and MSc. dissertations; the state and local drug standards; PubMed; CNKI; Scopus; the Web of Science; and Google Scholar using the keywords Coptis, Coptidis Rhizoma, Huanglian, and goldthread. Results: Currently, 128 chemical constituents have been isolated and identified from CR. Alkaloids are the characteristic components, together with organic acids, coumarins, phenylpropanoids and quinones. The extracts/compounds isolated from CR cover a wide pharmacological spectrum, including antibacterial, antivirus, antifungal, antidiabetic, anticancer and cardioprotective effects. Berberine is the most important active constituent and the primary toxic component of CR. Conclusions: As an important herbal medicine in Chinese medicine, CR has the potential to treat various diseases. However, further research should be undertaken to investigate the clinical effects, toxic constituents, target organs and pharmacokinetics, and to establish criteria for quality control, for CR and its related medications. In addition, the active constituents, other than alkaloids, in both raw and processed products of CR should be investigated.",2019 Apr 9,"['Wang, Jin', 'Wang, Lin', 'Lou, Guan-Hua', 'Zeng, Hai-Rong', 'Hu, Ju', 'Huang, Qin-Wan', 'Peng, Wei', 'Yang, Xiang-Bo']",Pharm Biol,,,True
6380762dca586738fd20d4b1c4bbdc3722a313aa,PMC,Crystal structure and activity-based labeling reveal the mechanisms for linkage-specific substrate recognition by deubiquitinase USP9X,http://dx.doi.org/10.1073/pnas.1815027116,PMC6462090,30914461,CC BY-NC-ND,"USP9X is a conserved deubiquitinase (DUB) that regulates multiple cellular processes. Dysregulation of USP9X has been linked to cancers and X-linked intellectual disability. Here, we report the crystal structure of the USP9X catalytic domain at 2.5-Å resolution. The structure reveals a canonical USP-fold comprised of fingers, palm, and thumb subdomains, as well as an unusual β-hairpin insertion. The catalytic triad of USP9X is aligned in an active configuration. USP9X is exclusively active against ubiquitin (Ub) but not Ub-like modifiers. Cleavage assays with di-, tri-, and tetraUb chains show that the USP9X catalytic domain has a clear preference for K11-, followed by K63-, K48-, and K6-linked polyUb chains. Using a set of activity-based diUb and triUb probes (ABPs), we demonstrate that the USP9X catalytic domain has an exo-cleavage preference for K48- and endo-cleavage preference for K11-linked polyUb chains. The structure model and biochemical data suggest that the USP9X catalytic domain harbors three Ub binding sites, and a zinc finger in the fingers subdomain and the β-hairpin insertion both play important roles in polyUb chain processing and linkage specificity. Furthermore, unexpected labeling of a secondary, noncatalytic cysteine located on a blocking loop adjacent to the catalytic site by K11-diUb ABP implicates a previously unreported mechanism of polyUb chain recognition. The structural features of USP9X revealed in our study are critical for understanding its DUB activity. The new Ub-based ABPs form a set of valuable tools to understand polyUb chain processing by the cysteine protease class of DUBs.",2019 Apr 9,"['Paudel, Prajwal', 'Zhang, Qi', 'Leung, Charles', 'Greenberg, Harrison C.', 'Guo, Yusong', 'Chern, Yi-Hsuan', 'Dong, Aiping', 'Li, Yanjun', 'Vedadi, Masoud', 'Zhuang, Zhihao', 'Tong, Yufeng']",Proc Natl Acad Sci U S A,,,True
7d3facc82a83039b3871ebb8a299bcdb9700156f,PMC,Crystal structure and activity-based labeling reveal the mechanisms for linkage-specific substrate recognition by deubiquitinase USP9X,http://dx.doi.org/10.1073/pnas.1815027116,PMC6462090,30914461,CC BY-NC-ND,"USP9X is a conserved deubiquitinase (DUB) that regulates multiple cellular processes. Dysregulation of USP9X has been linked to cancers and X-linked intellectual disability. Here, we report the crystal structure of the USP9X catalytic domain at 2.5-Å resolution. The structure reveals a canonical USP-fold comprised of fingers, palm, and thumb subdomains, as well as an unusual β-hairpin insertion. The catalytic triad of USP9X is aligned in an active configuration. USP9X is exclusively active against ubiquitin (Ub) but not Ub-like modifiers. Cleavage assays with di-, tri-, and tetraUb chains show that the USP9X catalytic domain has a clear preference for K11-, followed by K63-, K48-, and K6-linked polyUb chains. Using a set of activity-based diUb and triUb probes (ABPs), we demonstrate that the USP9X catalytic domain has an exo-cleavage preference for K48- and endo-cleavage preference for K11-linked polyUb chains. The structure model and biochemical data suggest that the USP9X catalytic domain harbors three Ub binding sites, and a zinc finger in the fingers subdomain and the β-hairpin insertion both play important roles in polyUb chain processing and linkage specificity. Furthermore, unexpected labeling of a secondary, noncatalytic cysteine located on a blocking loop adjacent to the catalytic site by K11-diUb ABP implicates a previously unreported mechanism of polyUb chain recognition. The structural features of USP9X revealed in our study are critical for understanding its DUB activity. The new Ub-based ABPs form a set of valuable tools to understand polyUb chain processing by the cysteine protease class of DUBs.",2019 Apr 9,"['Paudel, Prajwal', 'Zhang, Qi', 'Leung, Charles', 'Greenberg, Harrison C.', 'Guo, Yusong', 'Chern, Yi-Hsuan', 'Dong, Aiping', 'Li, Yanjun', 'Vedadi, Masoud', 'Zhuang, Zhihao', 'Tong, Yufeng']",Proc Natl Acad Sci U S A,,,True
b625ef49ed4b9e6f2d32150303199ca3fca8bddb,PMC,Characterization and bioactivity of self-assembled anti-angiogenic chondroitin sulfate-ES2-AF nanoparticle conjugate,http://dx.doi.org/10.2147/IJN.S195934,PMC6462165,31040673,CC BY-NC,"BACKGROUND: In the past few years, significant progress has been made in inhibiting neovascularization at the tumor site, cutting off the nutrient supply of the tumor, and inhibiting tumor growth and metastasis. However, many proteins/peptides have the disadvantage of poor stability, short half-life, and uncertain targeting ability. Chemical modification can be used to overcome these disadvantages; many polyethylene glycol-modified proteins/peptides have been approved by US FDA. The purpose of this study was to obtain a novel anti-angiogenic chondroitin sulfate (CS)-peptide nanoparticle conjugate with efficient anti-neovascularization and tumor targeting ability and an acceptable half-life. MATERIALS AND METHODS: The CS-ES2-AF nanoparticle conjugate was synthesized and characterized using (1)H-nuclear magnetic resonance spectroscopy, transmission electron microscopy, and particle size and zeta potential analyzer. The anti-angiogenic ability was studied using MTT, migration, tube formation, and chick chorioallantoic membrane assays. The targeting ability of CS-ES2-AF was studied by ELISA, surface plasmon resonance, and bioimaging. The pharmacokinetics was also studied. RESULTS: The CS-ES2-AF could self-assemble into stable nanoparticles in aqueous solution, which significantly enhances its anti-neovascularization activity, tumor targeting more explicit, and prolongs its half-life. CONCLUSION: CS is an effective protein/peptide modifier, and CS-ES2-AF displayed good potential in tumor targeting therapy.",2019 Apr 10,"['Xing, Liang', 'Sun, Feng', 'Wang, Zhendong', 'Li, Yan', 'Yang, Zhifang', 'Wang, Fengshan', 'Zhai, Guangxi', 'Tan, Haining']",Int J Nanomedicine,,,True
aeae7709de0f5cc24b6e055115c3105f44da9c61,PMC,"Qatar experience on One Health approach for middle-east respiratory syndrome coronavirus, 2012–2017: A viewpoint",http://dx.doi.org/10.1016/j.onehlt.2019.100090,PMC6462540,31011617,CC BY-NC-ND,"The emergence of the Middle East Respiratory Syndrome Corona Virus (MERS-CoV) in the Middle East in 2012 was associated with an overwhelming uncertainty about its epidemiological and clinical characteristics. Once dromedary camels (Camelus dromedarius) was found to be the natural reservoir of the virus, the public health systems across the Arabian Peninsula encountered an unprecedented pressure to control its transmission. This view point describes how the One Health approach was used in Qatar to manage the MERS-CoV outbreak during the period 2012–2017. One Health focuses on the association between the human, animals and environment sectors for total health and wellbeing of these three sectors. To manage the MERS outbreak in Qatar through a One Health approach, the Qatar National Outbreak Control Taskforce (OCT) was reactivated in November 2012. The animal health sector was invited to join the OCT. Later on, technical expertise was requested from the WHO, FAO, CDC, EMC, and PHE. Subsequently, a comprehensive One Health roadmap was delivered through leadership and coordination; surveillance and investigation; epidemiological studies and increase of local diagnostic capacity. The joint OCT, once trained had easy access to allocated resources and high risk areas to provide more evidence on the potential source of the virus and to investigate all reported cases within 24–48 h. Lack of sufficient technical guidance on veterinary surveillance and poor risk perception among the vulnerable population constituted major obstacles to maintain systematic One Health performance.",2019 Apr 4,"['Farag, Elmoubasher', 'Nour, Mohamed', 'Islam, Md. Mazharul', 'Mustafa, Aya', 'Khalid, Minahil', 'Sikkema, Reina S.', 'Alhajri, Forhud', 'Bu-Sayaa, Abdulla', 'Haroun, Mohamed', 'Van Kerkhove, Maria D.', 'Elkholy, Amgad', 'Malik, Sk. Mamunur R.', 'Reusken, Chantal', 'Koopmans, Marion', 'AlHajri, Mohd M.']",One Health,,,False
b530a3db1f7e6d6f289cd4fa3df8a782dcb691ab,PMC,The contribution of viruses and bacteria to community-acquired pneumonia in vaccinated children: a case–control study,http://dx.doi.org/10.1136/thoraxjnl-2018-212096,PMC6467248,30337417,CC BY-NC,"INTRODUCTION: Respiratory pathogens associated with childhood pneumonia are often detected in the upper respiratory tract of healthy children, making their contribution to pneumonia difficult to determine. We aimed to determine the contribution of common pathogens to pneumonia adjusting for rates of asymptomatic detection to inform future diagnosis, treatment and preventive strategies. METHODS: A case–control study was conducted among children <18 years in Perth, Western Australia. Cases were children hospitalised with radiologically confirmed pneumonia; controls were healthy children identified from outpatient and local immunisation clinics. Nasopharyngeal swabs were collected and tested for 14 respiratory viruses and 6 bacterial species by Polymerase chain reaction (PCR). For each pathogen, adjusted odds ratio (aOR; 95% CI) was calculated using multivariate logistic regression and population-attributable fraction (95% CI) for pneumonia was estimated. RESULTS: From May 2015 to October 2017, 230 cases and 230 controls were enrolled. At least one respiratory virus was identified in 57% of cases and 29% of controls (aOR: 4.7; 95% CI: 2.8 to 7.8). At least one bacterial species was detected in 72% of cases and 80% of controls (aOR: 0.7; 95% CI: 0.4 to 1.2). Respiratory syncytial virus (RSV) detection was most strongly associated with pneumonia (aOR: 58.4; 95% CI: 15.6 to 217.5). Mycoplasma pneumoniae was the only bacteria associated with pneumonia (aOR: 14.5; 95% CI: 2.2 to 94.8). We estimated that RSV, human metapneumovirus (HMPV), influenza, adenovirus and Mycoplasma pneumoniae were responsible for 20.2% (95% CI: 14.6 to 25.5), 9.8% (5.6% to 13.7%), 6.2% (2.5% to 9.7%), 4% (1.1% to 7.1%) and 7.2% (3.5% to 10.8%) of hospitalisations for childhood pneumonia, respectively. CONCLUSIONS: Respiratory viruses, particularly RSV and HMPV, are major contributors to pneumonia in Australian children.",2019 Mar 18,"['Bhuiyan, Mejbah Uddin', 'Snelling, Thomas L', 'West, Rachel', 'Lang, Jurissa', 'Rahman, Tasmina', 'Granland, Caitlyn', 'de Gier, Camilla', 'Borland, Meredith L', 'Thornton, Ruth B', 'Kirkham, Lea-Ann S', 'Sikazwe, Chisha', 'Martin, Andrew C', 'Richmond, Peter C', 'Smith, David W', 'Jaffe, Adam', 'Blyth, Christopher C']",Thorax,,,True
46e88010c4a926b35d981984c673bb834c17f7d2,PMC,2018 recommendations for the management of community acquired pneumonia,http://dx.doi.org/10.1590/S1806-37562018000000130,PMC6467584,30517341,CC BY-NC,"Community-acquired pneumonia (CAP) is the leading cause of death worldwide. Despite the vast diversity of respiratory microbiota, Streptococcus pneumoniae remains the most prevalent pathogen among etiologic agents. Despite the significant decrease in the mortality rates for lower respiratory tract infections in recent decades, CAP ranks third as a cause of death in Brazil. Since the latest Guidelines on CAP from the Sociedade Brasileira de Pneumologia e Tisiologia (SBPT, Brazilian Thoracic Association) were published (2009), there have been major advances in the application of imaging tests, in etiologic investigation, in risk stratification at admission and prognostic score stratification, in the use of biomarkers, and in the recommendations for antibiotic therapy (and its duration) and prevention through vaccination. To review these topics, the SBPT Committee on Respiratory Infections summoned 13 members with recognized experience in CAP in Brazil who identified issues relevant to clinical practice that require updates given the publication of new epidemiological and scientific evidence. Twelve topics concerning diagnostic, prognostic, therapeutic, and preventive issues were developed. The topics were divided among the authors, who conducted a nonsystematic review of the literature, but giving priority to major publications in the specific areas, including original articles, review articles, and systematic reviews. All authors had the opportunity to review and comment on all questions, producing a single final document that was approved by consensus.",2018 Sep-Oct,"['Corrêa, Ricardo de Amorim', 'Costa, Andre Nathan', 'Lundgren, Fernando', 'Michelin, Lessandra', 'Figueiredo, Mara Rúbia', 'Holanda, Marcelo', 'Gomes, Mauro', 'Teixeira, Paulo José Zimermann', 'Martins, Ricardo', 'Silva, Rodney', 'Athanazio, Rodrigo Abensur', 'da Silva, Rosemeri Maurici', 'Pereira, Mônica Corso']",J Bras Pneumol,,,True
4f16c5332bacc7ebdc6286893771ce195dd270de,PMC,IFITM3: How genetics influence influenza infection demographically,http://dx.doi.org/10.1016/j.bj.2019.01.004,PMC6468115,30987701,CC BY-NC-ND,"The role of host genetics in influenza infection is unclear despite decades of interest. Confounding factors such as age, sex, ethnicity and environmental factors have made it difficult to assess the role of genetics without influence. In recent years a single nucleotide polymorphism, interferon-induced transmembrane protein 3 (IFITM3) rs12252, has been shown to alter the severity of influenza infection in Asian populations. In this review we investigate this polymorphism as well as several others suggested to alter the host's defence against influenza infection. In addition, we highlight the open questions surrounding the viral restriction protein IFITM3 with the hope that by answering some of these questions we can elucidate the mechanism of IFITM3 viral restriction and therefore how this restriction is altered due to the rs12252 polymorphism.",2019 Feb 20,"['Wellington, Dannielle', 'Laurenson-Schafer, Henry', 'Abdel-Haq, Adi', 'Dong, Tao']",Biomed J,,,False
9e96c7b07f540611fcaccb80520fb7b3432d94b5,PMC,Emerging viruses and current strategies for vaccine intervention,http://dx.doi.org/10.1111/cei.13295,PMC6468171,30993690,CC BY-NC-ND,"During the past decade several notable viruses have suddenly emerged from obscurity or anonymity to become serious global health threats, provoking concern regarding their sustained epidemic transmission in immunologically naive human populations. With each new threat comes the call for rapid vaccine development. Indeed, vaccines are considered a critical component of disease prevention for emerging viral infections because, in many cases, other medical options are limited or non‐existent, or that infections result in such a rapid clinical deterioration that the effectiveness of therapeutics is limited. While classic approaches to vaccine development are still amenable to emerging viruses, the application of molecular techniques in virology has profoundly influenced our understanding of virus biology, and vaccination methods based on replicating, attenuated and non‐replicating virus vector approaches have become useful vaccine platforms. Together with a growing understanding of viral disease emergence, a range of vaccine strategies and international commitment to underpin development, vaccine intervention for new and emerging viruses may become a possibility.",2019 May 16,"['Afrough, B.', 'Dowall, S.', 'Hewson, R.']",Clin Exp Immunol,,,True
38550290e3c74a86fb0e56ecd69303ff68de55d9,PMC,Vaccines for emerging pathogens: from research to the clinic,http://dx.doi.org/10.1111/cei.13303,PMC6468174,30993689,CC BY-NC,"In this two‐part series of reviews, we have invited experts in their fields to contribute articles on the status of vaccine research and development for emerging pathogens. This topic has been brought into sharp focus in recent years following significant outbreaks of viral diseases such as those causing severe acute respiratory syndrome and Middle East respiratory syndrome, as well as devastating outbreaks of diseases caused by the Ebola, Marburg, Zika and Lassa fever viruses, to name only a few examples. Additionally, bacterial infections leading to bubonic and pneumonic plague, most notably in Madagascar in 2018, as well as malaria in many tropical countries, melioidosis in south east Asia and tularaemia in northern Europe and North America, have incurred significant morbidity and mortality. In this review series, the life cycle of these pathogens and the epidemiology of disease have been reviewed in the context of potential points of intervention for the prevention of human infection. Many of the emerging pathogens are zoonoses and, as such, there is scope for intervention at the animal/insect/environmental reservoir. Other pathogens covered in this review series are considered to be re‐emerging, such as multi‐drug resistant tuberculosis.",2019 May 16,"Williamson, E. D.",Clin Exp Immunol,,,True
9d8a94b596784c4280b895452b7f3d0e86b588b4,PMC,"Temporal trends in the incidence and demographics of cancers, communicable diseases, and non-communicable diseases in Saudi Arabia over the last decade",http://dx.doi.org/10.15537/smj.2019.3.23585,PMC6468216,30834424,CC BY-NC-SA,"OBJECTIVES: To describe the trends in the incidence rates of 5 most common cancers, communicable diseases, and non-communicable diseases in Saudi Arabia over the last decade. METHODS: The incidence rates of cancers (2001-2014), communicable diseases (2003-2016), and non-communicable diseases (1990-2017) were retrieved, classified, and analyzed retrospectively during November 2017, based on data available with the Ministry of Health and were analyzed at the Imam Abdulrahman Bin Faisal University in Dammam, Kingdom of Saudi Arabia. RESULTS: Age-standardized incidence rate (ASR) (per 100,000 population) of breast cancer among women increased dramatically from 11.8 in 2001 to 22.7 in 2014, indicating a 92.4% increase over the decade. Colorectal cancer incidence was the highest among men, and its ASR per 100,000 population increased from 5.0 to 10.6 in men and from 5.0 to 8.2 in women. Among communicable diseases, incidences of hepatitis B, measles, chickenpox, and brucellosis decreased while dengue fever increased. An alarming increase was observed in the incidence rate of non-communicable diseases namely, obesity, diabetes, and hypertension. CONCLUSION: The incidence rate of non-communicable diseases increased over the decade and was associated with increased mortality and disability, reduced quality of life, and increased health-care costs, indicating an urgent need to establish prevention and control programs. The rising trend in the incidence of cancers may also become a health care issue in Saudi Arabia in the coming years.",2019 Mar,"['Herzallah, Hatem K.', 'Antonisamy, Belavendra R.', 'Shafee, Mohammed H.', 'Al-Otaibi, Sultan T.']",Saudi Med J,,,True
c25e786759a5c261fed053aeeb9298e36b8aed17,PMC,"Noise and Room Acoustic Conditions in a Tertiary Referral Hospital, Seoul National University Hospital",http://dx.doi.org/10.7874/jao.2018.00269,PMC6468283,30989997,CC BY-NC,"BACKGROUND AND OBJECTIVES: Noise levels and room acoustic parameters at a tertiary referral hospital, Seoul National University Hospital (SNUH) in Korea, are investigated. MATERIALS AND METHODS: Through a questionnaire, acoustically problematic rooms are identified. Noise levels in emergency rooms (ERs) and intensive care units (ICUs) are measured over about three days. Acoustically critical and problematic rooms in the otolaryngology department are measured including examination rooms, operating rooms, nurse stations, receptions, and patient rooms. RESULTS: The A-weighted equivalent noise level, L(Aeq), ranges from 54 to 56 dBA, which is at least 10 dB lower than the noise levels of 65 to 73 dBA measured in American ERs. In an ICU, the noise level for the first night was 66 dBA, which came down to 56 dBA for the next day. The noise levels during three different ear surgeries vary from 57 to 62 dBA, depending on the use of surgical drills and suctions. The noise levels in a patient room is found to be 47 dBA, while the nurse stations and the receptions have high noise levels up to 64 dBA. The reverberation times in an operation room, examination room, and single patient room are found to be below 0.6 s. CONCLUSIONS: At SNUH, the nurse stations and receptions were found to be quite noisy. The ERs were quieter than in the previous studies. The measured reverberation times seemed low enough but some other nurse stations and examination rooms were not satisfactory according to the questionnaire.",2019 Apr 10,"['Cho, Wan-Ho', 'Jeong, Cheol-Ho', 'Chang, Ji-Ho', 'Lee, Seong-Hyun', 'Park, Moo Kyun', 'Suh, Myung-Whan', 'Han, Jae Joon']",J Audiol Otol,,,True
471aa6c890ce013986b2f55f65bde5b06615f456,PMC,Dominant LMAN2L mutation causes intellectual disability with remitting epilepsy,http://dx.doi.org/10.1002/acn3.727,PMC6469342,31020005,CC BY-NC-ND,"Mis‐secreted glycoproteins (LGI1, reelin) are emerging causes of epilepsy. LMAN2L belongs to a glycoprotein secretion chaperone family. One recessive LMAN2L missense mutation predicted to impair the chaperone's interaction with glycoproteins was reported in a family with intellectual disability (ID) and remitting epilepsy. We describe four members of a family with autosomal dominant inheritance of a similar phenotype. We show that they segregate a NM_001142292.1:c.1073delT mutation that eliminates LMAN2L's endoplasmic reticulum retention signal and mislocalizes the protein from that compartment to the plasma membrane. LMAN2L mislocalization, like impaired glycoprotein interaction, disturbs brain development, including generation of developmentally restricted epilepsy.",2019 Mar 7,"['Alkhater, Reem A.', 'Wang, Peixiang', 'Ruggieri, Alessandra', 'Israelian, Lori', 'Walker, Susan', 'Scherer, Stephen W.', 'Smith, Mary Lou', 'Minassian, Berge A.']",Ann Clin Transl Neurol,,,True
2a2a9ae443755df9e1d930c75c2023f0b1780a51,PMC,The role of lateral pterygoid muscle in the traumatic temporomandibular joint ankylosis: A gene chip based analysis,http://dx.doi.org/10.3892/mmr.2019.10078,PMC6471772,30942403,CC BY-NC-ND,"Traumatic temporomandibular joint ankylosis (TMJA) is a common disease and disorder of the temporomandibular joint (TMJ); however, its pathogenesis has yet to be completely elucidated. In the authors' previous studies, the lateral pterygoid muscle (LPM) was confirmed to exert a function in distraction osteogenesis (DO) during the healing of a condylar fracture, which resulted in the formation of excess bone. The aim of the present study was to investigate alterations in the expression of any associated genes via an Affymetrix GeneChip method. The traumatic TMJA model was fabricated by a condylar fracture in the TMJ area of sheep with either a dissected LPM (LPD) or normal (LPN). The untreated sheep served as a control. At 4- and 12 weeks post-surgery, the condylar zone was isolated to perform the gene chip analysis, which was performed according to a standard Affymetrix protocol. The validated genes were further evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The gene chip analysis indicated that the LPN gene expression pattern was similar compared with the DO process, while LPD was similar to that of normal bone fracture healing. The validated genes were collagen type II α1 chain, C-type lectin domain family 3 member A, interleukin 1A, cartilage oligomeric matrix protein, chondromodulin (LECT1), calcitonin receptor (CALCR), transforming growth factor (TGF)-β1, Fos proto-oncogene (FOS), bone γ-carboxyglutamate protein and bone morphogenic protein (BMP)7, among which, BMP7, LECT1, CALCR and FOS were confirmed by RT-qPCR. In conclusion, the present study demonstrated that LPM exerts a DO effect during the pathogenesis of traumatic TMJA, which may provide a novel target for preventing TMJA.",2019 May 22,"['Zhang, Jianying', 'Sun, Xiangzhao', 'Jia, Sen', 'Jiang, Xin', 'Deng, Tiange', 'Liu, Ping', 'Hu, Kaijin']",Mol Med Rep,,,True
c6e1ce0bd3692673434c291e76fd1f545a4115b7,PMC,The role of lateral pterygoid muscle in the traumatic temporomandibular joint ankylosis: A gene chip based analysis,http://dx.doi.org/10.3892/mmr.2019.10078,PMC6471772,30942403,CC BY-NC-ND,"Traumatic temporomandibular joint ankylosis (TMJA) is a common disease and disorder of the temporomandibular joint (TMJ); however, its pathogenesis has yet to be completely elucidated. In the authors' previous studies, the lateral pterygoid muscle (LPM) was confirmed to exert a function in distraction osteogenesis (DO) during the healing of a condylar fracture, which resulted in the formation of excess bone. The aim of the present study was to investigate alterations in the expression of any associated genes via an Affymetrix GeneChip method. The traumatic TMJA model was fabricated by a condylar fracture in the TMJ area of sheep with either a dissected LPM (LPD) or normal (LPN). The untreated sheep served as a control. At 4- and 12 weeks post-surgery, the condylar zone was isolated to perform the gene chip analysis, which was performed according to a standard Affymetrix protocol. The validated genes were further evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The gene chip analysis indicated that the LPN gene expression pattern was similar compared with the DO process, while LPD was similar to that of normal bone fracture healing. The validated genes were collagen type II α1 chain, C-type lectin domain family 3 member A, interleukin 1A, cartilage oligomeric matrix protein, chondromodulin (LECT1), calcitonin receptor (CALCR), transforming growth factor (TGF)-β1, Fos proto-oncogene (FOS), bone γ-carboxyglutamate protein and bone morphogenic protein (BMP)7, among which, BMP7, LECT1, CALCR and FOS were confirmed by RT-qPCR. In conclusion, the present study demonstrated that LPM exerts a DO effect during the pathogenesis of traumatic TMJA, which may provide a novel target for preventing TMJA.",2019 May 22,"['Zhang, Jianying', 'Sun, Xiangzhao', 'Jia, Sen', 'Jiang, Xin', 'Deng, Tiange', 'Liu, Ping', 'Hu, Kaijin']",Mol Med Rep,,,False
8509342038d6b5c6a8a9d980bf207a83f37cd970,PMC,Patient-Centeredness during In-Depth Consultation in the Outpatient Clinic of a Tertiary Hospital in Korea: Paradigm Shift from Disease to Patient,http://dx.doi.org/10.3346/jkms.2019.34.e119,PMC6473096,31001936,CC BY-NC,"BACKGROUND: Patient-centered care (PCC) and integrative care approach are widely advocated. However, their implementation usually requires an extended consultation time. Despite significant advances in medical diagnosis and treatment, no studies have examined consultation time and patient centeredness in Korea. METHODS: We conducted a “15-Minute Consultation” for first-time patients in outpatient clinics of 13 departments. A control group was selected from the same physicians' first-time patients, adjusting for age and gender. A total of 275 patients were selected for receiving in-depth consultation and 141 control patients were selected for regular consultation. Data were collected from patients using a questionnaire comprising a patient-centeredness scale and items on potential predictors such as socio-demographic and clinical factors. We also investigated the participating physician's professionalism. RESULTS: As compared to the control group, the in-depth consultation group scored higher on 5 variables associated with PCC, including (patients' perception of) medical professionals, wait and consultation times, treatment, patient advocacy, and patient satisfaction. While 92.4% of patients in the in-depth consultation group reported that the consultation time was sufficient, only 69.0% of those in the control group reported the same (P < 0.01). In the in-depth consultation group, scores on satisfaction level were the highest for the department of internal medicine, followed by departments of surgery and pediatrics. Participating physicians' improved satisfaction following the intervention proved that in-depth consultation facilitated building a rapport with patients. CONCLUSION: This study illustrated that the provision of sufficiently long consultation for serious and rare diseases could improve PCC and physicians' professionalism. Health authorities should reshuffle the healthcare delivery system and provide sufficient consultation time to ensure PCC and medical professionalism.",2019 Apr 9,"['Sohn, Kyoung-Hee', 'Nam, Sarah', 'Joo, Jungmin', 'Kwon, Yong Jin', 'Yim, Jae-Joon']",J Korean Med Sci,,,True
104e60eede9e4016c243f20f4541a33852ea3d1c,PMC,"Respiratory syncytial virus-associated seizures in Korean children, 2011–2016",http://dx.doi.org/10.3345/kjp.2018.07066,PMC6477548,30360041,CC BY-NC,"PURPOSE: Respiratory syncytial virus (RSV) infection can cause various neurological complications. This study aimed to investigate the RSV-associated neurologic manifestations that present with seizures. METHODS: We retrospectively reviewed the medical records of patients aged less than 15 years with laboratory-confirmed RSV infections and seizures between January 2011 and December 2016 in a regional hospital in South Korea. RESULTS: During this period, 1,193 patients with laboratory-confirmed RSV infection were identified. Of these, 35 (35 of 1,193, 2.93%; boys, 19; girls, 16; mean age: 20.8±16.6 months) presented with seizure. Febrile seizure was the most common diagnosis (27 of 35, 77.1%); simple febrile seizures in 13 patients (13 of 27, 48.1%) and complex febrile seizures in 14 (14 of 27, 51.9%). Afebrile seizures without meningitis or encephalopathy were observed in 5 patients (5 of 35, 14.3%), seizures with meningitis in 2 (2 of 35, 5.7%), and seizure with encephalopathy in 1 (1 of 35, 2.9%) patient. Lower respiratory symptoms were not observed in 8 patients. In a patient with encephalopathy, brain diffusion-weighted magnetic resonance imaging revealed transient changes in white matter, suggesting cytotoxic edema as the mechanism underlying encephalopathy. Most patients recovered with general management, and progression to epilepsy was noted in only 1 patient. CONCLUSION: Although febrile seizures are the most common type of seizure associated with RSV infection, the proportion of patients with complex febrile seizures was higher than that of those with general febrile seizures. Transient cytotoxic edema may be a pathogenic mechanism in RSV-related encephalopathy with seizures.",2019 Apr 23,"['Cha, Teahyen', 'Choi, Young Jin', 'Oh, Jae-Won', 'Kim, Chang-Ryul', 'Park, Dong Woo', 'Seol, In Joon', 'Moon, Jin-Hwa']",Korean J Pediatr,,,True
1141866ae787a8da15454e7301841b05b5e19525,PMC,Assessing health systems in Guinea for prevention and control of priority zoonotic diseases: A One Health approach,http://dx.doi.org/10.1016/j.onehlt.2019.100093,PMC6479159,31049389,CC BY-NC-ND,"To guide One Health capacity building efforts in the Republic of Guinea in the wake of the 2014–2016 Ebola virus disease (EVD) outbreak, we sought to identify and assess the existing systems and structures for zoonotic disease detection and control. We partnered with the government ministries responsible for human, animal, and environmental health to identify a list of zoonotic diseases – rabies, anthrax, brucellosis, viral hemorrhagic fevers, trypanosomiasis and highly pathogenic avian influenza – as the country's top priorities. We used each priority disease as a case study to identify existing processes for prevention, surveillance, diagnosis, laboratory confirmation, reporting and response across the three ministries. Results were used to produce disease-specific systems “maps” emphasizing linkages across the systems, as well as opportunities for improvement. We identified brucellosis as a particularly neglected condition. Past efforts to build avian influenza capabilities, which had degraded substantially in less than a decade, highlighted the challenge of sustainability. We observed a keen interest across sectors to reinvigorate national rabies control, and given the regional and global support for One Health approaches to rabies elimination, rabies could serve as an ideal disease to test incipient One Health coordination mechanisms and procedures. Overall, we identified five major categories of gaps and challenges: (1) Coordination; (2) Training; (3) Infrastructure; (4) Public Awareness; and (5) Research. We developed and prioritized recommendations to address the gaps, estimated the level of resource investment needed, and estimated a timeline for implementation. These prioritized recommendations can be used by the Government of Guinea to plan strategically for future One Health efforts, ideally under the auspices of the national One Health Platform. This work demonstrates an effective methodology for mapping systems and structures for zoonotic diseases, and the benefit of conducting a baseline review of systemic capabilities prior to embarking on capacity building efforts.",2019 Apr 16,"['Standley, Claire J.', 'Carlin, Ellen P.', 'Sorrell, Erin M.', 'Barry, Alpha M.', 'Bile, Ebi', 'Diakite, Aboubacar S.', 'Keita, Mamady S.', 'Koivogui, Lamine', 'Mane, Seny', 'Martel, Lise D.', 'Katz, Rebecca']",One Health,,,False
fc3ea6bcece82db1a8217d73e4d64bb848661135,PMC,Assessing health systems in Guinea for prevention and control of priority zoonotic diseases: A One Health approach,http://dx.doi.org/10.1016/j.onehlt.2019.100093,PMC6479159,31049389,CC BY-NC-ND,"To guide One Health capacity building efforts in the Republic of Guinea in the wake of the 2014–2016 Ebola virus disease (EVD) outbreak, we sought to identify and assess the existing systems and structures for zoonotic disease detection and control. We partnered with the government ministries responsible for human, animal, and environmental health to identify a list of zoonotic diseases – rabies, anthrax, brucellosis, viral hemorrhagic fevers, trypanosomiasis and highly pathogenic avian influenza – as the country's top priorities. We used each priority disease as a case study to identify existing processes for prevention, surveillance, diagnosis, laboratory confirmation, reporting and response across the three ministries. Results were used to produce disease-specific systems “maps” emphasizing linkages across the systems, as well as opportunities for improvement. We identified brucellosis as a particularly neglected condition. Past efforts to build avian influenza capabilities, which had degraded substantially in less than a decade, highlighted the challenge of sustainability. We observed a keen interest across sectors to reinvigorate national rabies control, and given the regional and global support for One Health approaches to rabies elimination, rabies could serve as an ideal disease to test incipient One Health coordination mechanisms and procedures. Overall, we identified five major categories of gaps and challenges: (1) Coordination; (2) Training; (3) Infrastructure; (4) Public Awareness; and (5) Research. We developed and prioritized recommendations to address the gaps, estimated the level of resource investment needed, and estimated a timeline for implementation. These prioritized recommendations can be used by the Government of Guinea to plan strategically for future One Health efforts, ideally under the auspices of the national One Health Platform. This work demonstrates an effective methodology for mapping systems and structures for zoonotic diseases, and the benefit of conducting a baseline review of systemic capabilities prior to embarking on capacity building efforts.",2019 Apr 16,"['Standley, Claire J.', 'Carlin, Ellen P.', 'Sorrell, Erin M.', 'Barry, Alpha M.', 'Bile, Ebi', 'Diakite, Aboubacar S.', 'Keita, Mamady S.', 'Koivogui, Lamine', 'Mane, Seny', 'Martel, Lise D.', 'Katz, Rebecca']",One Health,,,False
e0e8648de04f7d9e69558253b2a663585a11bee5,PMC,Assessing health systems in Guinea for prevention and control of priority zoonotic diseases: A One Health approach,http://dx.doi.org/10.1016/j.onehlt.2019.100093,PMC6479159,31049389,CC BY-NC-ND,"To guide One Health capacity building efforts in the Republic of Guinea in the wake of the 2014–2016 Ebola virus disease (EVD) outbreak, we sought to identify and assess the existing systems and structures for zoonotic disease detection and control. We partnered with the government ministries responsible for human, animal, and environmental health to identify a list of zoonotic diseases – rabies, anthrax, brucellosis, viral hemorrhagic fevers, trypanosomiasis and highly pathogenic avian influenza – as the country's top priorities. We used each priority disease as a case study to identify existing processes for prevention, surveillance, diagnosis, laboratory confirmation, reporting and response across the three ministries. Results were used to produce disease-specific systems “maps” emphasizing linkages across the systems, as well as opportunities for improvement. We identified brucellosis as a particularly neglected condition. Past efforts to build avian influenza capabilities, which had degraded substantially in less than a decade, highlighted the challenge of sustainability. We observed a keen interest across sectors to reinvigorate national rabies control, and given the regional and global support for One Health approaches to rabies elimination, rabies could serve as an ideal disease to test incipient One Health coordination mechanisms and procedures. Overall, we identified five major categories of gaps and challenges: (1) Coordination; (2) Training; (3) Infrastructure; (4) Public Awareness; and (5) Research. We developed and prioritized recommendations to address the gaps, estimated the level of resource investment needed, and estimated a timeline for implementation. These prioritized recommendations can be used by the Government of Guinea to plan strategically for future One Health efforts, ideally under the auspices of the national One Health Platform. This work demonstrates an effective methodology for mapping systems and structures for zoonotic diseases, and the benefit of conducting a baseline review of systemic capabilities prior to embarking on capacity building efforts.",2019 Apr 16,"['Standley, Claire J.', 'Carlin, Ellen P.', 'Sorrell, Erin M.', 'Barry, Alpha M.', 'Bile, Ebi', 'Diakite, Aboubacar S.', 'Keita, Mamady S.', 'Koivogui, Lamine', 'Mane, Seny', 'Martel, Lise D.', 'Katz, Rebecca']",One Health,,,False
2f2d45c91cb9bc3c2884d4edb8b9e62786468b97,PMC,Assessing health systems in Guinea for prevention and control of priority zoonotic diseases: A One Health approach,http://dx.doi.org/10.1016/j.onehlt.2019.100093,PMC6479159,31049389,CC BY-NC-ND,"To guide One Health capacity building efforts in the Republic of Guinea in the wake of the 2014–2016 Ebola virus disease (EVD) outbreak, we sought to identify and assess the existing systems and structures for zoonotic disease detection and control. We partnered with the government ministries responsible for human, animal, and environmental health to identify a list of zoonotic diseases – rabies, anthrax, brucellosis, viral hemorrhagic fevers, trypanosomiasis and highly pathogenic avian influenza – as the country's top priorities. We used each priority disease as a case study to identify existing processes for prevention, surveillance, diagnosis, laboratory confirmation, reporting and response across the three ministries. Results were used to produce disease-specific systems “maps” emphasizing linkages across the systems, as well as opportunities for improvement. We identified brucellosis as a particularly neglected condition. Past efforts to build avian influenza capabilities, which had degraded substantially in less than a decade, highlighted the challenge of sustainability. We observed a keen interest across sectors to reinvigorate national rabies control, and given the regional and global support for One Health approaches to rabies elimination, rabies could serve as an ideal disease to test incipient One Health coordination mechanisms and procedures. Overall, we identified five major categories of gaps and challenges: (1) Coordination; (2) Training; (3) Infrastructure; (4) Public Awareness; and (5) Research. We developed and prioritized recommendations to address the gaps, estimated the level of resource investment needed, and estimated a timeline for implementation. These prioritized recommendations can be used by the Government of Guinea to plan strategically for future One Health efforts, ideally under the auspices of the national One Health Platform. This work demonstrates an effective methodology for mapping systems and structures for zoonotic diseases, and the benefit of conducting a baseline review of systemic capabilities prior to embarking on capacity building efforts.",2019 Apr 16,"['Standley, Claire J.', 'Carlin, Ellen P.', 'Sorrell, Erin M.', 'Barry, Alpha M.', 'Bile, Ebi', 'Diakite, Aboubacar S.', 'Keita, Mamady S.', 'Koivogui, Lamine', 'Mane, Seny', 'Martel, Lise D.', 'Katz, Rebecca']",One Health,,,False
d1fcc874f5dea992525479e321f0eced236b7e7c,PMC,Assessing health systems in Guinea for prevention and control of priority zoonotic diseases: A One Health approach,http://dx.doi.org/10.1016/j.onehlt.2019.100093,PMC6479159,31049389,CC BY-NC-ND,"To guide One Health capacity building efforts in the Republic of Guinea in the wake of the 2014–2016 Ebola virus disease (EVD) outbreak, we sought to identify and assess the existing systems and structures for zoonotic disease detection and control. We partnered with the government ministries responsible for human, animal, and environmental health to identify a list of zoonotic diseases – rabies, anthrax, brucellosis, viral hemorrhagic fevers, trypanosomiasis and highly pathogenic avian influenza – as the country's top priorities. We used each priority disease as a case study to identify existing processes for prevention, surveillance, diagnosis, laboratory confirmation, reporting and response across the three ministries. Results were used to produce disease-specific systems “maps” emphasizing linkages across the systems, as well as opportunities for improvement. We identified brucellosis as a particularly neglected condition. Past efforts to build avian influenza capabilities, which had degraded substantially in less than a decade, highlighted the challenge of sustainability. We observed a keen interest across sectors to reinvigorate national rabies control, and given the regional and global support for One Health approaches to rabies elimination, rabies could serve as an ideal disease to test incipient One Health coordination mechanisms and procedures. Overall, we identified five major categories of gaps and challenges: (1) Coordination; (2) Training; (3) Infrastructure; (4) Public Awareness; and (5) Research. We developed and prioritized recommendations to address the gaps, estimated the level of resource investment needed, and estimated a timeline for implementation. These prioritized recommendations can be used by the Government of Guinea to plan strategically for future One Health efforts, ideally under the auspices of the national One Health Platform. This work demonstrates an effective methodology for mapping systems and structures for zoonotic diseases, and the benefit of conducting a baseline review of systemic capabilities prior to embarking on capacity building efforts.",2019 Apr 16,"['Standley, Claire J.', 'Carlin, Ellen P.', 'Sorrell, Erin M.', 'Barry, Alpha M.', 'Bile, Ebi', 'Diakite, Aboubacar S.', 'Keita, Mamady S.', 'Koivogui, Lamine', 'Mane, Seny', 'Martel, Lise D.', 'Katz, Rebecca']",One Health,,,False
46c2b3f4e85af8b1e30ac3c5be7b72a1412eec46,PMC,"Disaster preparedness for earthquakes in hemodialysis units in Gyeongju and Pohang, South Korea",http://dx.doi.org/10.23876/j.krcp.18.0058,PMC6481979,30776874,CC BY-NC-ND,"In 2016 and 2017, there were earthquakes greater than 5.0 in magnitude on the Korean Peninsula, which has previously been considered an earthquake-free zone. Patients with chronic kidney disease are particularly vulnerable to earthquakes, as the term “renal disaster” suggests. In the event of a major earthquake, patients on hemodialysis face the risk of losing maintenance dialysis due to infrastructure disruption. In this review, we share the experience of an earthquake in Pohang that posed a serious risk to patients on hemodialysis. We review the disaster response system in Japan and propose a disaster preparedness plan with respect to hemodialysis. Korean nephrologists and staff in dialysis facilities should be trained in emergency response to mitigate risk from natural disasters. Dialysis staff should be familiar with the action plan for natural disaster events that disrupt hemodialysis, such as outages and water treatment system failures caused by earthquakes. Patients on hemodialysis also need to be educated about disaster preparedness. In the event of a disaster situation that results in dialysis failure, patients need to know what to do. At the local and national government level, long-term preparations should be made to handle renal disaster and patient safety logistics. Moreover, Korean nephrologists should also be prepared to manage cardiovascular disease and diabetes in disaster situations. Further evaluation and management of social and national disaster preparedness of hemodialysis units to earthquakes in Korea are needed.",2019 Mar 18,"['Yoo, Kyung Don', 'Kim, Hyo Jin', 'Kim, Yunmi', 'Park, Jae Yoon', 'Shin, Sung Joon', 'Han, Seung Hyeok', 'Kim, Dong Ki', 'Lim, Chun Soo', 'Kim, Yon Su']",Kidney Res Clin Pract,,,True
e6cb0165f7a39a1721da4e100aee26666a5e5c50,PMC,Rebound stridor in children with croup after nebulised adrenaline: does it really exist?,http://dx.doi.org/10.1183/20734735.0011-2019,PMC6481985,31031839,CC BY-NC,Rebound stridor after the use of nebulised adrenaline does not exist http://ow.ly/aoOd30o5lEo,2019 Mar,"['Sakthivel, Muthukumar', 'Elkashif, Sami', 'Al Ansari, Khalid', 'Powell, Colin V.E.']",Breathe (Sheff),,,True
60cc55d9df1b0ff215bcaefe413b7b6edc5eb182,PMC,Memory immune responses and protection of chickens against a nephropathogenic infectious bronchitis virus strain by combining live heterologous and inactivated homologous vaccines,http://dx.doi.org/10.1292/jvms.18-0065,PMC6483904,30867350,CC BY-NC-ND,"In this study, we evaluated antibody and cell-mediated immune (CMI) responses in the mucosal and systemic compartments and protection against challenge with a nephropathogenic Brazilian (BR-I) strain of infectious bronchitis virus (IBV) in chickens submitted to a vaccination regime comprising a priming dose of heterologous live attenuated Massachusetts vaccine followed by a booster dose of an experimental homologous inactivated vaccine two weeks later. This immunization protocol elicited significant increases in serum and lachrymal levels of anti-IBV IgG antibodies and upregulated the expression of CMI response genes, such as those encoding CD8β chain and Granzyme homolog A in tracheal and kidney tissues at 3, 7, and 11 days post-infection in the vaccinated chickens. Additionally, vaccinated and challenged chickens showed reduced viral loads and microscopic lesion counts in tracheal and kidney tissues, and their antibody and CMI responses were negatively correlated with viral loads in the trachea and kidney. In conclusion, the combination of live attenuated vaccine containing the Massachusetts strain with a booster dose of an inactivated vaccine, containing a BR-I IBV strain, confers effective protection against infection with nephropathogenic homologous IBV strain because of the induction of consistent memory immune responses mediated by IgG antibodies and TCD8 cells in the mucosal and systemic compartments of chickens submitted to this vaccination regime.",2019 Apr 12,"['dos SANTOS, Romeu Moreira', 'FERNANDO, Filipe Santos', 'MONTASSIER, Maria de Fátima Silva', 'SILVA, Ketherson Rodrigues', 'LOPES, Priscila Diniz', 'PAVANI, Caren', 'BORZI, Mariana Monezi', 'OKINO, Cintia Hiromi', 'MONTASSIER, Helio José']",J Vet Med Sci,,,True
9cda860c97d430aea207a063d13e8612e023320c,PMC,Assessment of the cost effectiveness of compulsory testing of introduced animals and bulk tank milk testing for bovine viral diarrhea in Japan,http://dx.doi.org/10.1292/jvms.18-0671,PMC6483914,30828031,CC BY-NC-ND,"Bovine viral diarrhea (BVD) is a chronic disease of cattle caused by infection with BVD virus (BVDV) and can result in economic losses within the livestock industry. In Japan, the test and culling policy is a basic control measure, and implementation of an adequate vaccination program is recommended as a national policy. In addition, optional control measures, including compulsory testing of introduced animals and bulk tank milk (BTM) testing as a mass screening method, are used in several provinces, but their efficacy has not been completely assessed. We evaluated these control measures using the scenario tree model of BVD in Japan, developed in the previous study. The model outputs indicated that compulsory testing of all introduced cattle, rather than only heifers and/or non-vaccinated cattle, was cost effective and reduced the risk of BVDV introduction due to animal movement and that BTM testing could effectively monitor most part of the cattle population. Vaccination coverage and BVDV prevalence among introduced cattle could also affect the cost effectiveness of compulsory testing of targeted cattle, particularly under low vaccination coverage or high BVDV prevalence. However, even with the implementation of a highly effective monitoring scheme for many years, BVD risk could not be eliminated; it instead converged at a very low level (0.02%). Disease models with a cost-effective output could be a powerful tool in developing a control scheme for chronic animal diseases, including BVD, with the consent of relevant stakeholders.",2019 Apr 1,"['ISODA, Norikazu', 'ASANO, Akihiro', 'ICHIJO, Michiru', 'OHNO, Hiroshi', 'SATO, Kazuhiko', 'OKAMOTO, Hirokazu', 'NAKAO, Shigeru', 'KATO, Hajime', 'SAITO, Kazuma', 'ITO, Naoki', 'USUI, Akira', 'TAKAYAMA, Hiroaki', 'SAKODA, Yoshihiro']",J Vet Med Sci,,,True
066178ded1d6d540be366e6468bc01e78e605a81,PMC,Repeated avian infectious bronchitis virus infections within a single chicken farm,http://dx.doi.org/10.1292/jvms.18-0722,PMC6483923,30828040,CC BY-NC-ND,"Genotyping of avian infectious bronchitis virus (IBV) was performed on trachea and kidney samples of six chickens obtained from a single farm in Japan. Using two primer sets targeting the spike (S) protein gene, the S1 and S2 regions of DNA fragments were amplified. Sequences of amplified S1 fragments extracted from both organs were identical among the six chickens, showing a JP-I genotype. Sequences of amplified S2 fragments differed between trachea and kidney samples. The kidney profile showed a group IV genotype, whereas the trachea profile showed an unclassified group. This result showed that two different IBVs infected the six chickens. The first IBV infection induced poor protective immunity in this farm, permitting a second IBV infection to occur.",2019 Apr 4,"['KATO, Atsushi', 'OGURO, Shiori', 'KURIHARA, Yukino', 'KOJIMA, Hiroe', 'INAYOSHI, Yujin', 'LIN, Zhifeng', 'SASAKAWA, Chihiro', 'SHIBUYA, Kazumoto']",J Vet Med Sci,,,True
65648f466638ba2c4b63d49a1c46e834719890a5,PMC,Nested–polymerase chain reaction detection of Pneumocystis carinii f. sp. canis in a suspected immunocompromised Cavalier King Charles spaniel with multiple infections,http://dx.doi.org/10.1177/2050313X19841169,PMC6487761,31065354,CC BY-NC,"A 7-month-old Cavalier King Charles Spaniel female was referred due to a chronic cough refractory to antibiotic treatments. Laboratory findings showed leukocytosis, increased serum C-reactive protein, hypogammaglobulinemia, and decreased total serum immunoglobulin G concentration. Thoracic radiographs showed a mild bronchial pattern. Cytology of the bronchoalveolar lavage fluid revealed a septic inflammation. Bordetella bronchiseptica, Mycoplasma spp., and Pneumocystis carinii were identified by polymerase chain reaction testing, and Klebsiella pneumonia was cultured from the bronchoalveolar lavage fluid. Moreover, Escherichia coli was also cultured from urine. Pneumocystis spp. identification was done by sequencing of genetic amplicons. The dog died due to cardiopulmonary arrest secondary to a spontaneous pneumothorax on the day following the procedure. This report documents the detection of Pneumocystis carinii f. sp. canis in a suspected immunocompromised Cavalier King Charles Spaniel with concurrent pulmonary and urinary tract infections involving four different pathogens, and highlights the importance of the use of polymerase chain reaction testing to detect canine Pneumocystis spp. in cases with negative bronchoalveolar lavage cytology.",2019 Apr 26,"['Petini, Matteo', 'Furlanello, Tommaso', 'Danesi, Patrizia', 'Zoia, Andrea']",SAGE Open Med Case Rep,,,True
81b7b68d85bd6af03d993351bdc5d94c7ae814e2,PMC,Metabolic programming of macrophage functions and pathogens control,http://dx.doi.org/10.1016/j.redox.2019.101198,PMC6488820,31048245,CC BY-NC-ND,"Macrophages (Mφ) are central players in mediating proinflammatory and immunomodulatory functions. Unchecked Mφ activities contribute to pathology across many diseases, including those caused by infectious pathogens and metabolic disorders. A fine balance of Mφ responses is crucial, which may be achieved by enforcing appropriate bioenergetics pathways. Metabolism serves as the provider of energy, substrates, and byproducts that support differential Mφ characteristics. The metabolic properties that control the polarization and response of Mφ remain to be fully uncovered for use in managing infectious diseases. Here, we review the various metabolic states in Mφ and how they influence the cell function.",2019 Apr 20,"['Koo, Sue-jie', 'Garg, Nisha J.']",Redox Biol,,,False
5a0937374802cad6f72576fb6c511715aa884b18,PMC,Evaluation of prognosis related to compliance with supportive periodontal treatment in patients with chronic periodontitis: a clinical retrospective study,http://dx.doi.org/10.5051/jpis.2019.49.2.76,PMC6494772,31098329,CC BY-NC,"PURPOSE: The purpose of this study was to evaluate the prognostic effect of patient compliance with supportive periodontal treatment (PC-SPT). Chronic periodontitis patients were classified based on their compliance level, and factors affecting PC-SPT and the prognosis of PC-SPT were investigated. METHODS: This study selected 206 patients who started SPT after receiving periodontal treatment between 2010 and 2012. Patients who continued SPT through February 2016 were included. The patients were classified according to whether they exhibited complete compliance (100% of visits), excellent compliance (≥70% of visits), incomplete compliance (<70% of visits), or non-compliance (only 2 visits). Patient characteristics that could affect PC-SPT, such as age, sex, distance of the clinic from their residence, implantation, and periodontal treatment, were investigated. The number of newly decayed and extracted teeth, alveolar bone level changes around the teeth and implants, and implant removal were examined to evaluate the prognosis of PC-SPT. RESULTS: Sex and the presence of an implant significantly affected PC-SPT. Additionally, the number of newly decayed and extracted teeth and changes in alveolar bone levels around the teeth and implants were significant prognostic factors related to PC-SPT. CONCLUSIONS: PC-SPT in chronic periodontitis patients will help maintain periodontal health and prevent further periodontal disease.",2019 Apr 17,"['Lee, Jong-Bin', 'Shin, Hye-Jung', 'Kim, Dae-Yeob', 'Pang, Eun-Kyoung']",J Periodontal Implant Sci,,,True
5d4f1f02d0e731966dddd635e8fa7bfdc169d3b9,PMC,A Rare Case of Autoimmune Polyglandular Syndrome Type 2 in a Child With Persistent Fatigue,http://dx.doi.org/10.1177/2333794X19845074,PMC6498771,31080849,CC BY-NC,"Adrenal insufficiency is a rare, potentially life-threatening condition whose diagnosis requires a high index of suspicion. Adrenal insufficiency may be primary, secondary, or tertiary with varied etiologies. Primary insufficiency may be part of a cluster of autoimmune diseases, referred to as autoimmune polyglandular syndrome(s) (APS). We describe a case of a 15-year-old male who presents to a local emergency department complaining of fatigue, fever, abdominal pain, nausea, and vomiting for a few days with a preceding viral illness. The patient was hyponatremic and hyperkalemic with skin hyperpigmentation, raising concern for adrenal insufficiency. Laboratory workup confirmed autoimmune primary adrenal insufficiency, with subsequent laboratory studies revealing autoimmune thyroiditis and celiac disease. Concomitant Addison’s and Hashimoto’s diseases led to a diagnosis of APS type 2. The patient was started on steroid replacement with rapid clinical improvement.",2019 May 1,"['Smith, Ryan Kenneth', 'Gerrits, Peter M.']",Glob Pediatr Health,,,True
c39ece828769a97d7ab743e5bae232bc127ae6a3,PMC,The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression,http://dx.doi.org/10.1016/j.celrep.2019.03.063,PMC6499400,30995476,CC BY-NC-ND,"Many viruses shut off host gene expression to inhibit antiviral responses. Viral proteins and host proteins required for viral replication are typically spared in this process, but the mechanisms of target selectivity during host shutoff remain poorly understood. Using transcriptome-wide and targeted reporter experiments, we demonstrate that the influenza A virus endoribonuclease PA-X usurps RNA splicing to selectively target host RNAs for destruction. Proximity-labeling proteomics reveals that PA-X interacts with cellular RNA processing proteins, some of which are partially required for host shutoff. Thus, PA-X taps into host nuclear pre-mRNA processing mechanisms to destroy nascent mRNAs shortly after their synthesis. This mechanism sets PA-X apart from other viral host shutoff proteins that target actively translating mRNAs in the cytoplasm. Our study reveals a unique mechanism of host shutoff that helps us understand how influenza viruses suppress host gene expression.",2019 Apr 16,"['Gaucherand, Lea', 'Porter, Brittany K.', 'Levene, Rachel E.', 'Price, Emma L.', 'Schmaling, Summer K.', 'Rycroft, Chris H.', 'Kevorkian, Yuzo', 'McCormick, Craig', 'Khaperskyy, Denys A.', 'Gaglia, Marta M.']",Cell Rep,,,True
8da197323d31294840253b501f434273767f1a5f,PMC,The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression,http://dx.doi.org/10.1016/j.celrep.2019.03.063,PMC6499400,30995476,CC BY-NC-ND,"Many viruses shut off host gene expression to inhibit antiviral responses. Viral proteins and host proteins required for viral replication are typically spared in this process, but the mechanisms of target selectivity during host shutoff remain poorly understood. Using transcriptome-wide and targeted reporter experiments, we demonstrate that the influenza A virus endoribonuclease PA-X usurps RNA splicing to selectively target host RNAs for destruction. Proximity-labeling proteomics reveals that PA-X interacts with cellular RNA processing proteins, some of which are partially required for host shutoff. Thus, PA-X taps into host nuclear pre-mRNA processing mechanisms to destroy nascent mRNAs shortly after their synthesis. This mechanism sets PA-X apart from other viral host shutoff proteins that target actively translating mRNAs in the cytoplasm. Our study reveals a unique mechanism of host shutoff that helps us understand how influenza viruses suppress host gene expression.",2019 Apr 16,"['Gaucherand, Lea', 'Porter, Brittany K.', 'Levene, Rachel E.', 'Price, Emma L.', 'Schmaling, Summer K.', 'Rycroft, Chris H.', 'Kevorkian, Yuzo', 'McCormick, Craig', 'Khaperskyy, Denys A.', 'Gaglia, Marta M.']",Cell Rep,,,False
0ae1cad5b20badf8dcea32e8c80209b8948d1e49,PMC,The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression,http://dx.doi.org/10.1016/j.celrep.2019.03.063,PMC6499400,30995476,CC BY-NC-ND,"Many viruses shut off host gene expression to inhibit antiviral responses. Viral proteins and host proteins required for viral replication are typically spared in this process, but the mechanisms of target selectivity during host shutoff remain poorly understood. Using transcriptome-wide and targeted reporter experiments, we demonstrate that the influenza A virus endoribonuclease PA-X usurps RNA splicing to selectively target host RNAs for destruction. Proximity-labeling proteomics reveals that PA-X interacts with cellular RNA processing proteins, some of which are partially required for host shutoff. Thus, PA-X taps into host nuclear pre-mRNA processing mechanisms to destroy nascent mRNAs shortly after their synthesis. This mechanism sets PA-X apart from other viral host shutoff proteins that target actively translating mRNAs in the cytoplasm. Our study reveals a unique mechanism of host shutoff that helps us understand how influenza viruses suppress host gene expression.",2019 Apr 16,"['Gaucherand, Lea', 'Porter, Brittany K.', 'Levene, Rachel E.', 'Price, Emma L.', 'Schmaling, Summer K.', 'Rycroft, Chris H.', 'Kevorkian, Yuzo', 'McCormick, Craig', 'Khaperskyy, Denys A.', 'Gaglia, Marta M.']",Cell Rep,,,True
ad8c7c22faa32a928133bfeb767353400262040c,PMC,Understanding perceptions of global healthcare experiences on provider values and practices in the USA: a qualitative study among global health physicians and program directors,http://dx.doi.org/10.1136/bmjopen-2018-026020,PMC6500299,30948593,CC BY-NC,"OBJECTIVES: The study aimed to qualitatively examine the perspectives of US-based physicians and academic global health programme leaders on how global health work shapes their viewpoints, values and healthcare practices back in the USA. DESIGN: A prospective, qualitative exploratory study that employed online questionnaires and open-ended, semi-structured interviews with two participant groups: (1) global health physicians and (2) global health programme leaders affiliated with USA-based academic medical centres. Open coding procedures and thematic content analysis were used to analyse data and derive themes for discussion. PARTICIPANTS: 159 global health physicians and global health programme leaders at 25 academic medical institutions were invited via email to take a survey and participate in a follow-up interview. Twelve participants completed online questionnaires (7.5% response rate) and eight participants (four survey participants and four additionally recruited participants) participated in in-depth, in-person or phone semi-structured interviews. RESULTS: Five themes emerged that highlight how global health physicians and academic global health programme leaders perceive global health work abroad in shaping USA-based medical practices: (1) a sense of improved patient rapport, particularly with low-income, refugee and immigrant patients, and improved and more engaged patient care; (2) reduced spending on healthcare services; (3) greater awareness of the social determinants of health; (4) deeper understanding of the USA’s healthcare system compared with systems in other countries; and (5) a reinforcement of values that initially motivated physicians to pursue work in global health. CONCLUSIONS: A majority of participating global health physicians and programme leaders believed that international engagements improved patient care back in the USA. Participant responses relating to the five themes were contextualised by highlighting factors that simultaneously impinge on their ability to provide improved patient care, such as the social determinants of health, and the challenges of changing USA healthcare policy.",2019 Apr 3,"['Matthews-Trigg, Nathaniel', 'Citrin, David', 'Halliday, Scott', 'Acharya, Bibhav', 'Maru, Sheela', 'Bezruchka, Stephen', 'Maru, Duncan']",BMJ Open,,,True
c7ec0563ddbb18f183ddbd147056d8a2aca9fef2,PMC,Understanding perceptions of global healthcare experiences on provider values and practices in the USA: a qualitative study among global health physicians and program directors,http://dx.doi.org/10.1136/bmjopen-2018-026020,PMC6500299,30948593,CC BY-NC,"OBJECTIVES: The study aimed to qualitatively examine the perspectives of US-based physicians and academic global health programme leaders on how global health work shapes their viewpoints, values and healthcare practices back in the USA. DESIGN: A prospective, qualitative exploratory study that employed online questionnaires and open-ended, semi-structured interviews with two participant groups: (1) global health physicians and (2) global health programme leaders affiliated with USA-based academic medical centres. Open coding procedures and thematic content analysis were used to analyse data and derive themes for discussion. PARTICIPANTS: 159 global health physicians and global health programme leaders at 25 academic medical institutions were invited via email to take a survey and participate in a follow-up interview. Twelve participants completed online questionnaires (7.5% response rate) and eight participants (four survey participants and four additionally recruited participants) participated in in-depth, in-person or phone semi-structured interviews. RESULTS: Five themes emerged that highlight how global health physicians and academic global health programme leaders perceive global health work abroad in shaping USA-based medical practices: (1) a sense of improved patient rapport, particularly with low-income, refugee and immigrant patients, and improved and more engaged patient care; (2) reduced spending on healthcare services; (3) greater awareness of the social determinants of health; (4) deeper understanding of the USA’s healthcare system compared with systems in other countries; and (5) a reinforcement of values that initially motivated physicians to pursue work in global health. CONCLUSIONS: A majority of participating global health physicians and programme leaders believed that international engagements improved patient care back in the USA. Participant responses relating to the five themes were contextualised by highlighting factors that simultaneously impinge on their ability to provide improved patient care, such as the social determinants of health, and the challenges of changing USA healthcare policy.",2019 Apr 3,"['Matthews-Trigg, Nathaniel', 'Citrin, David', 'Halliday, Scott', 'Acharya, Bibhav', 'Maru, Sheela', 'Bezruchka, Stephen', 'Maru, Duncan']",BMJ Open,,,True
ad8c7c22faa32a928133bfeb767353400262040c,PMC,Understanding perceptions of global healthcare experiences on provider values and practices in the USA: a qualitative study among global health physicians and program directors,http://dx.doi.org/10.1136/bmjopen-2018-026020,PMC6500299,30948593,CC BY-NC,"OBJECTIVES: The study aimed to qualitatively examine the perspectives of US-based physicians and academic global health programme leaders on how global health work shapes their viewpoints, values and healthcare practices back in the USA. DESIGN: A prospective, qualitative exploratory study that employed online questionnaires and open-ended, semi-structured interviews with two participant groups: (1) global health physicians and (2) global health programme leaders affiliated with USA-based academic medical centres. Open coding procedures and thematic content analysis were used to analyse data and derive themes for discussion. PARTICIPANTS: 159 global health physicians and global health programme leaders at 25 academic medical institutions were invited via email to take a survey and participate in a follow-up interview. Twelve participants completed online questionnaires (7.5% response rate) and eight participants (four survey participants and four additionally recruited participants) participated in in-depth, in-person or phone semi-structured interviews. RESULTS: Five themes emerged that highlight how global health physicians and academic global health programme leaders perceive global health work abroad in shaping USA-based medical practices: (1) a sense of improved patient rapport, particularly with low-income, refugee and immigrant patients, and improved and more engaged patient care; (2) reduced spending on healthcare services; (3) greater awareness of the social determinants of health; (4) deeper understanding of the USA’s healthcare system compared with systems in other countries; and (5) a reinforcement of values that initially motivated physicians to pursue work in global health. CONCLUSIONS: A majority of participating global health physicians and programme leaders believed that international engagements improved patient care back in the USA. Participant responses relating to the five themes were contextualised by highlighting factors that simultaneously impinge on their ability to provide improved patient care, such as the social determinants of health, and the challenges of changing USA healthcare policy.",2019 Apr 3,"['Matthews-Trigg, Nathaniel', 'Citrin, David', 'Halliday, Scott', 'Acharya, Bibhav', 'Maru, Sheela', 'Bezruchka, Stephen', 'Maru, Duncan']",BMJ Open,,,True
1ddb1bf28b7a62037dc736e2dc7692460467a20a,PMC,Understanding perceptions of global healthcare experiences on provider values and practices in the USA: a qualitative study among global health physicians and program directors,http://dx.doi.org/10.1136/bmjopen-2018-026020,PMC6500299,30948593,CC BY-NC,"OBJECTIVES: The study aimed to qualitatively examine the perspectives of US-based physicians and academic global health programme leaders on how global health work shapes their viewpoints, values and healthcare practices back in the USA. DESIGN: A prospective, qualitative exploratory study that employed online questionnaires and open-ended, semi-structured interviews with two participant groups: (1) global health physicians and (2) global health programme leaders affiliated with USA-based academic medical centres. Open coding procedures and thematic content analysis were used to analyse data and derive themes for discussion. PARTICIPANTS: 159 global health physicians and global health programme leaders at 25 academic medical institutions were invited via email to take a survey and participate in a follow-up interview. Twelve participants completed online questionnaires (7.5% response rate) and eight participants (four survey participants and four additionally recruited participants) participated in in-depth, in-person or phone semi-structured interviews. RESULTS: Five themes emerged that highlight how global health physicians and academic global health programme leaders perceive global health work abroad in shaping USA-based medical practices: (1) a sense of improved patient rapport, particularly with low-income, refugee and immigrant patients, and improved and more engaged patient care; (2) reduced spending on healthcare services; (3) greater awareness of the social determinants of health; (4) deeper understanding of the USA’s healthcare system compared with systems in other countries; and (5) a reinforcement of values that initially motivated physicians to pursue work in global health. CONCLUSIONS: A majority of participating global health physicians and programme leaders believed that international engagements improved patient care back in the USA. Participant responses relating to the five themes were contextualised by highlighting factors that simultaneously impinge on their ability to provide improved patient care, such as the social determinants of health, and the challenges of changing USA healthcare policy.",2019 Apr 3,"['Matthews-Trigg, Nathaniel', 'Citrin, David', 'Halliday, Scott', 'Acharya, Bibhav', 'Maru, Sheela', 'Bezruchka, Stephen', 'Maru, Duncan']",BMJ Open,,,False
85f7430c807f1334c2b9c5621304e9e7fa8ad64a,PMC,"Efficacy and safety of Chou-Ling-Dan granules in the treatment of seasonal influenza via combining Western and traditional Chinese medicine: protocol for a multicentre, randomised controlled clinical trial",http://dx.doi.org/10.1136/bmjopen-2018-024800,PMC6500347,30944133,CC BY-NC,"INTRODUCTION: Chou-Ling-Dan (CLD) (Laggerapterodonta) granules are an ethnic herbal medicine from Yunnan province of China. CLD granules have been used for the treatment of inflammatory conditions and feverish diseases in China, including seasonal influenza, but few evidence-based medicine (EBM) clinical studies have been conducted to assess its efficacy and safety in the treatment of influenza. Here, we performed an EBM clinical trial combining Western Chinese medicine and traditional Chinese medicine (TCM) evaluation systems to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza. METHODS AND ANALYSIS: The study is designed as a multicentre, randomised, double-blinded, double-simulation, oseltamivir-controlled and placebo-controlled, parallel-design clinical trial. Eligible subjects (n=318) will be allocated after satisfying the criteria (Western medicine). Subjects will be randomised to receive CLD granules, oseltamivir, or a placebo for 5 days of treatment and with follow-up after treatment to record symptoms and signs and to collect pharyngeal/throat swabs and serum samples for detecting the virus and antibodies. At the same time, the syndrome differentiation criteria of TCM, such as tongue body, furred tongue and type of pulse, will be recorded as determined by doctors of both Western and Chinese medicine. Participants will be instructed to comply with the protocol and to keep a daily record of symptoms. The primary and secondary outcomes and safety indicators will be used to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza based on both Western Chinese medicine and TCM evaluation systems. ETHICS AND DISSEMINATION: The CLD granules clinical trial will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice and has been approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT02662426; Pre-results.",2019 Apr 2,"['He, Jiayang', 'Li, Zhengtu', 'Huang, Wanyi', 'Guan, Wenda', 'Ma, Hongxia', 'Yang, Zi feng', 'Wang, Xinhua']",BMJ Open,,,True
500e585afac01e4b3847aa138db86b04352484c5,PMC,"Efficacy and safety of Chou-Ling-Dan granules in the treatment of seasonal influenza via combining Western and traditional Chinese medicine: protocol for a multicentre, randomised controlled clinical trial",http://dx.doi.org/10.1136/bmjopen-2018-024800,PMC6500347,30944133,CC BY-NC,"INTRODUCTION: Chou-Ling-Dan (CLD) (Laggerapterodonta) granules are an ethnic herbal medicine from Yunnan province of China. CLD granules have been used for the treatment of inflammatory conditions and feverish diseases in China, including seasonal influenza, but few evidence-based medicine (EBM) clinical studies have been conducted to assess its efficacy and safety in the treatment of influenza. Here, we performed an EBM clinical trial combining Western Chinese medicine and traditional Chinese medicine (TCM) evaluation systems to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza. METHODS AND ANALYSIS: The study is designed as a multicentre, randomised, double-blinded, double-simulation, oseltamivir-controlled and placebo-controlled, parallel-design clinical trial. Eligible subjects (n=318) will be allocated after satisfying the criteria (Western medicine). Subjects will be randomised to receive CLD granules, oseltamivir, or a placebo for 5 days of treatment and with follow-up after treatment to record symptoms and signs and to collect pharyngeal/throat swabs and serum samples for detecting the virus and antibodies. At the same time, the syndrome differentiation criteria of TCM, such as tongue body, furred tongue and type of pulse, will be recorded as determined by doctors of both Western and Chinese medicine. Participants will be instructed to comply with the protocol and to keep a daily record of symptoms. The primary and secondary outcomes and safety indicators will be used to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza based on both Western Chinese medicine and TCM evaluation systems. ETHICS AND DISSEMINATION: The CLD granules clinical trial will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice and has been approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT02662426; Pre-results.",2019 Apr 2,"['He, Jiayang', 'Li, Zhengtu', 'Huang, Wanyi', 'Guan, Wenda', 'Ma, Hongxia', 'Yang, Zi feng', 'Wang, Xinhua']",BMJ Open,,,True
488c028f6d7b11c0eda9224a28685fcc192e151e,PMC,"Efficacy and safety of Chou-Ling-Dan granules in the treatment of seasonal influenza via combining Western and traditional Chinese medicine: protocol for a multicentre, randomised controlled clinical trial",http://dx.doi.org/10.1136/bmjopen-2018-024800,PMC6500347,30944133,CC BY-NC,"INTRODUCTION: Chou-Ling-Dan (CLD) (Laggerapterodonta) granules are an ethnic herbal medicine from Yunnan province of China. CLD granules have been used for the treatment of inflammatory conditions and feverish diseases in China, including seasonal influenza, but few evidence-based medicine (EBM) clinical studies have been conducted to assess its efficacy and safety in the treatment of influenza. Here, we performed an EBM clinical trial combining Western Chinese medicine and traditional Chinese medicine (TCM) evaluation systems to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza. METHODS AND ANALYSIS: The study is designed as a multicentre, randomised, double-blinded, double-simulation, oseltamivir-controlled and placebo-controlled, parallel-design clinical trial. Eligible subjects (n=318) will be allocated after satisfying the criteria (Western medicine). Subjects will be randomised to receive CLD granules, oseltamivir, or a placebo for 5 days of treatment and with follow-up after treatment to record symptoms and signs and to collect pharyngeal/throat swabs and serum samples for detecting the virus and antibodies. At the same time, the syndrome differentiation criteria of TCM, such as tongue body, furred tongue and type of pulse, will be recorded as determined by doctors of both Western and Chinese medicine. Participants will be instructed to comply with the protocol and to keep a daily record of symptoms. The primary and secondary outcomes and safety indicators will be used to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza based on both Western Chinese medicine and TCM evaluation systems. ETHICS AND DISSEMINATION: The CLD granules clinical trial will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice and has been approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT02662426; Pre-results.",2019 Apr 2,"['He, Jiayang', 'Li, Zhengtu', 'Huang, Wanyi', 'Guan, Wenda', 'Ma, Hongxia', 'Yang, Zi feng', 'Wang, Xinhua']",BMJ Open,,,True
213a8c23f78d46b373ed3f00cb04fadd6256f954,PMC,"Efficacy and safety of Chou-Ling-Dan granules in the treatment of seasonal influenza via combining Western and traditional Chinese medicine: protocol for a multicentre, randomised controlled clinical trial",http://dx.doi.org/10.1136/bmjopen-2018-024800,PMC6500347,30944133,CC BY-NC,"INTRODUCTION: Chou-Ling-Dan (CLD) (Laggerapterodonta) granules are an ethnic herbal medicine from Yunnan province of China. CLD granules have been used for the treatment of inflammatory conditions and feverish diseases in China, including seasonal influenza, but few evidence-based medicine (EBM) clinical studies have been conducted to assess its efficacy and safety in the treatment of influenza. Here, we performed an EBM clinical trial combining Western Chinese medicine and traditional Chinese medicine (TCM) evaluation systems to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza. METHODS AND ANALYSIS: The study is designed as a multicentre, randomised, double-blinded, double-simulation, oseltamivir-controlled and placebo-controlled, parallel-design clinical trial. Eligible subjects (n=318) will be allocated after satisfying the criteria (Western medicine). Subjects will be randomised to receive CLD granules, oseltamivir, or a placebo for 5 days of treatment and with follow-up after treatment to record symptoms and signs and to collect pharyngeal/throat swabs and serum samples for detecting the virus and antibodies. At the same time, the syndrome differentiation criteria of TCM, such as tongue body, furred tongue and type of pulse, will be recorded as determined by doctors of both Western and Chinese medicine. Participants will be instructed to comply with the protocol and to keep a daily record of symptoms. The primary and secondary outcomes and safety indicators will be used to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza based on both Western Chinese medicine and TCM evaluation systems. ETHICS AND DISSEMINATION: The CLD granules clinical trial will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice and has been approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT02662426; Pre-results.",2019 Apr 2,"['He, Jiayang', 'Li, Zhengtu', 'Huang, Wanyi', 'Guan, Wenda', 'Ma, Hongxia', 'Yang, Zi feng', 'Wang, Xinhua']",BMJ Open,,,False
2a5b2e11c10d35b22cb2965f62ccc79e61eeb77b,PMC,"Hepatitis B: Prevalence, Hope",,PMC6500415,31073252,CC BY-NC-SA,,2019 May 27,"['Hedley-Whyte, John', 'Milamed, Debra R.']",Ulster Med J,,,True
dec136aeb4b48f3a2f506fa208d892cbe3ccd4af,PMC,"Occurrence of infectious bronchitis in layer birds in Plateau state, north central Nigeria",http://dx.doi.org/10.4314/ovj.v9i1.13,PMC6500855,31086770,CC BY-NC,"A flock of 54 wk-old layer birds exhibiting signs of respiratory distress, greenish diarrhea, and drop in egg production was investigated. A marked drop in egg production (55%) was recorded with eggs appearing white and soft-shelled. Mortality was in the range of 1%–2% with post-mortem lesions revealing cloudy air sacs, frothy, and congested lungs. Viral RNA was extracted from pooled tissue samples (trachea, lungs, spleen, and liver) and tested for Avian influenza virus (AIV), Newcastle disease virus (NDV), and infectious bronchitis virus (IBV) by reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, virus isolation was attempted in 9–11 day-old embryonating chicken eggs (ECE). In order to determine the prevalence of IBV serotype(s) in the flock, serum samples were screened by hemagglutination-inhibition (HI) test using IBV antigens and antisera (Arkansas, Connecticut, and Massachusetts). Neither AIV nor NDV but IBV was detected in the tissue samples by RT-PCR. In addition, virus isolate obtained after four serial passages in ECE produced dwarfed, stunted, and hemorrhagic embryos, and the isolate was confirmed by RT-PCR to be IBV. The serum samples were 100% seropositive for three serotypes with HI titres ranging from 5 to 12 Log(2). In this study, IBV was confirmed as the causative agent of the observed respiratory distress and drop in egg production. Also, the evidence of co-circulation of multiple IBV serotypes was established, this to the best of our knowledge is the first of such report in Nigeria. We recommend extensive molecular and sero-epidemiology of circulating IBV genotypes and serotypes in Nigeria with the aim of developing better control strategies, including vaccination.",2019 Apr 16,"['Shittu, Ismaila', 'Gado, Dorcas A.', 'Meseko, Clement A.', 'Nyam, Davou C.', 'Olawuyi, Kayode A.', 'Moses, Gyang D.', 'Chinyere, Chinonoyerem N.', 'Joannis, Tony M.']",Open Vet J,,,True
3edd89544597d9f178b831aa1047475fe3910871,PMC,A water-focused one-health approach for early detection and prevention of viral outbreaks,http://dx.doi.org/10.1016/j.onehlt.2019.100094,PMC6501061,31080867,CC BY-NC-ND,"Despite consistent efforts to protect public health there is still a heavy burden of viral disease, both in the United States and abroad. In addition to conventional medical treatment, there is a need for a holistic approach for early detection and prevention of viral outbreaks at a population level. One-Health is a relatively new integrative approach to the solving of global health challenges. A key component to the One-Health approach is the notion that human health, animal health, and environmental health are all innately interrelated. One-Health interventions, initiated by veterinary doctors, have proven to be effective in controlling outbreaks, but thus far the applications focus on zoonotic viruses transmitted from animals to humans. Environmental engineers and environmental scientists hold a critical role in the further development of One-Health approaches that include water-related transport and transmission of human, animal, and zoonotic viruses. In addition to waterborne viruses, the proposed approach is applicable to a wide range of viruses that are found in human excrement since contaminated water-based surveillance systems may be used for early detection of viral disease. This paper proposes a greater One-Health based framework that involves water-related pathways. The first step in the proposed framework is the identification of critical exposure pathways of viruses in the water environment. Identification of critical pathways informs the second and third steps, which include water-based surveillance systems for early detection at a population level and implementation of intervention approaches to block the critical pathways of exposure.",2019 Apr 20,"[""O'Brien, Evan"", 'Xagoraraki, Irene']",One Health,,,False
4af614b04d5df393575c749cd953aa3855fa8b44,PMC,Perceptions of postoutbreak management by management and healthcare workers of a Middle East respiratory syndrome outbreak in a tertiary care hospital: a qualitative study,http://dx.doi.org/10.1136/bmjopen-2017-017476,PMC6502063,31061009,CC BY-NC,"OBJECTIVES: This study examines perceptions of the operational and organisational management of a major outbreak of Middle East Respiratory Syndrome (MERS) caused by a novel coronavirus (MERS-CoV) in the Kingdom of Saudi Arabia (KSA). Perspectives were sought from key decision-makers and clinical staff about the factors perceived to promote and inhibit effective and rapid control of the outbreak. SETTING: A large teaching tertiary healthcare centre in KSA; the outbreak lasted 6 weeks from June 2015. PARTICIPANTS: Data were collected via individual and focus group interviews with 28 key informant participants (9 management decision-makers and 19 frontline healthcare workers). DESIGN: We used qualitative methods of process evaluation to examine perceptions of the outbreak and the factors contributing to, or detracting from successful management. Data were analysed using qualitative thematic content analysis. RESULTS: Five themes and 15 subthemes were found. The themes were related to: (1) the high stress of the outbreak, (2) factors perceived to contribute to outbreak occurrence, (3) factors perceived to contribute to success of outbreak control, (4) factors inhibiting outbreak control and (5) long-term institutional gains in response to the outbreak management. CONCLUSION: Management of the MERS-CoV outbreak at King Abdulaziz Medical City-Riyadh was widely recognised by staff as a serious outbreak of local and national significance. While the outbreak was controlled successfully in 6 weeks, progress in management was inhibited by a lack of institutional readiness to implement infection control (IC) measures and reduce patient flow, low staff morale and high anxiety. Effective management was promoted by greater involvement of all staff in sharing learning and knowledge of the outbreak, developing trust and teamwork and harnessing collective leadership. Future major IC crises could be improved via measures to strengthen these areas, better coordination of media management and proactive staff counselling and support.",2019 May 5,"['Al Knawy, Bandar Abdulmohsen', 'Al-Kadri, Hanan M F', 'Elbarbary, Mahmoud', 'Arabi, Yaseen', 'Balkhy, Hanan H', 'Clark, Alex']",BMJ Open,,,True
59c84e06ac8246b44efc595cafef84b946f24219,PMC,Perceptions of postoutbreak management by management and healthcare workers of a Middle East respiratory syndrome outbreak in a tertiary care hospital: a qualitative study,http://dx.doi.org/10.1136/bmjopen-2017-017476,PMC6502063,31061009,CC BY-NC,"OBJECTIVES: This study examines perceptions of the operational and organisational management of a major outbreak of Middle East Respiratory Syndrome (MERS) caused by a novel coronavirus (MERS-CoV) in the Kingdom of Saudi Arabia (KSA). Perspectives were sought from key decision-makers and clinical staff about the factors perceived to promote and inhibit effective and rapid control of the outbreak. SETTING: A large teaching tertiary healthcare centre in KSA; the outbreak lasted 6 weeks from June 2015. PARTICIPANTS: Data were collected via individual and focus group interviews with 28 key informant participants (9 management decision-makers and 19 frontline healthcare workers). DESIGN: We used qualitative methods of process evaluation to examine perceptions of the outbreak and the factors contributing to, or detracting from successful management. Data were analysed using qualitative thematic content analysis. RESULTS: Five themes and 15 subthemes were found. The themes were related to: (1) the high stress of the outbreak, (2) factors perceived to contribute to outbreak occurrence, (3) factors perceived to contribute to success of outbreak control, (4) factors inhibiting outbreak control and (5) long-term institutional gains in response to the outbreak management. CONCLUSION: Management of the MERS-CoV outbreak at King Abdulaziz Medical City-Riyadh was widely recognised by staff as a serious outbreak of local and national significance. While the outbreak was controlled successfully in 6 weeks, progress in management was inhibited by a lack of institutional readiness to implement infection control (IC) measures and reduce patient flow, low staff morale and high anxiety. Effective management was promoted by greater involvement of all staff in sharing learning and knowledge of the outbreak, developing trust and teamwork and harnessing collective leadership. Future major IC crises could be improved via measures to strengthen these areas, better coordination of media management and proactive staff counselling and support.",2019 May 5,"['Al Knawy, Bandar Abdulmohsen', 'Al-Kadri, Hanan M F', 'Elbarbary, Mahmoud', 'Arabi, Yaseen', 'Balkhy, Hanan H', 'Clark, Alex']",BMJ Open,,,True
54e6685af0e34a4bff348e1ea79e1e2e4bde3b1a,PMC,Perceptions of postoutbreak management by management and healthcare workers of a Middle East respiratory syndrome outbreak in a tertiary care hospital: a qualitative study,http://dx.doi.org/10.1136/bmjopen-2017-017476,PMC6502063,31061009,CC BY-NC,"OBJECTIVES: This study examines perceptions of the operational and organisational management of a major outbreak of Middle East Respiratory Syndrome (MERS) caused by a novel coronavirus (MERS-CoV) in the Kingdom of Saudi Arabia (KSA). Perspectives were sought from key decision-makers and clinical staff about the factors perceived to promote and inhibit effective and rapid control of the outbreak. SETTING: A large teaching tertiary healthcare centre in KSA; the outbreak lasted 6 weeks from June 2015. PARTICIPANTS: Data were collected via individual and focus group interviews with 28 key informant participants (9 management decision-makers and 19 frontline healthcare workers). DESIGN: We used qualitative methods of process evaluation to examine perceptions of the outbreak and the factors contributing to, or detracting from successful management. Data were analysed using qualitative thematic content analysis. RESULTS: Five themes and 15 subthemes were found. The themes were related to: (1) the high stress of the outbreak, (2) factors perceived to contribute to outbreak occurrence, (3) factors perceived to contribute to success of outbreak control, (4) factors inhibiting outbreak control and (5) long-term institutional gains in response to the outbreak management. CONCLUSION: Management of the MERS-CoV outbreak at King Abdulaziz Medical City-Riyadh was widely recognised by staff as a serious outbreak of local and national significance. While the outbreak was controlled successfully in 6 weeks, progress in management was inhibited by a lack of institutional readiness to implement infection control (IC) measures and reduce patient flow, low staff morale and high anxiety. Effective management was promoted by greater involvement of all staff in sharing learning and knowledge of the outbreak, developing trust and teamwork and harnessing collective leadership. Future major IC crises could be improved via measures to strengthen these areas, better coordination of media management and proactive staff counselling and support.",2019 May 5,"['Al Knawy, Bandar Abdulmohsen', 'Al-Kadri, Hanan M F', 'Elbarbary, Mahmoud', 'Arabi, Yaseen', 'Balkhy, Hanan H', 'Clark, Alex']",BMJ Open,,,False
4f161faa8e707f7ec698d9c9a9790249d8d90171,PMC,Perceptions of postoutbreak management by management and healthcare workers of a Middle East respiratory syndrome outbreak in a tertiary care hospital: a qualitative study,http://dx.doi.org/10.1136/bmjopen-2017-017476,PMC6502063,31061009,CC BY-NC,"OBJECTIVES: This study examines perceptions of the operational and organisational management of a major outbreak of Middle East Respiratory Syndrome (MERS) caused by a novel coronavirus (MERS-CoV) in the Kingdom of Saudi Arabia (KSA). Perspectives were sought from key decision-makers and clinical staff about the factors perceived to promote and inhibit effective and rapid control of the outbreak. SETTING: A large teaching tertiary healthcare centre in KSA; the outbreak lasted 6 weeks from June 2015. PARTICIPANTS: Data were collected via individual and focus group interviews with 28 key informant participants (9 management decision-makers and 19 frontline healthcare workers). DESIGN: We used qualitative methods of process evaluation to examine perceptions of the outbreak and the factors contributing to, or detracting from successful management. Data were analysed using qualitative thematic content analysis. RESULTS: Five themes and 15 subthemes were found. The themes were related to: (1) the high stress of the outbreak, (2) factors perceived to contribute to outbreak occurrence, (3) factors perceived to contribute to success of outbreak control, (4) factors inhibiting outbreak control and (5) long-term institutional gains in response to the outbreak management. CONCLUSION: Management of the MERS-CoV outbreak at King Abdulaziz Medical City-Riyadh was widely recognised by staff as a serious outbreak of local and national significance. While the outbreak was controlled successfully in 6 weeks, progress in management was inhibited by a lack of institutional readiness to implement infection control (IC) measures and reduce patient flow, low staff morale and high anxiety. Effective management was promoted by greater involvement of all staff in sharing learning and knowledge of the outbreak, developing trust and teamwork and harnessing collective leadership. Future major IC crises could be improved via measures to strengthen these areas, better coordination of media management and proactive staff counselling and support.",2019 May 5,"['Al Knawy, Bandar Abdulmohsen', 'Al-Kadri, Hanan M F', 'Elbarbary, Mahmoud', 'Arabi, Yaseen', 'Balkhy, Hanan H', 'Clark, Alex']",BMJ Open,,,False
a4f39fce76a00087b57733d4da58e67b49966eae,PMC,Ciliocytophthoria of nasal epithelial cells after viral infection: a sign of suffering cell,http://dx.doi.org/10.23750/abm.v90i2-S.8103,PMC6502078,30715030,CC BY-NC-SA,"Ciliocytophthoria (CCP) defines a degenerative process of the ciliated cells consequent to viral infections, and it is characterized by typical morphological changes. We evaluated the distinct and characteristic phases of CCP, by means of the optical microscopy of the nasal mucosa (nasal cytology), in 20 patients (12 males and 8 females; aged between 18 and 40 years). Three phases of CCP by nasal cytology are detected. This outcome confirms that CCP represents a sign of suffering nasal epithelial cell. (www.actabiomedica.it)",2019,"['Matteo, Gelardi', 'Giorgio, Ciprandi']",Acta Biomed,,,True
f9738261ac322d052e519fb1f1297eedc917a939,PMC,Human metapneumovirus in Pediatric Patients with Acute Respiratory Tract Infections in the Aseer Region of Saudi Arabia,http://dx.doi.org/10.4103/sjmms.sjmms_72_18,PMC6503696,31080387,CC BY-NC-SA,"BACKGROUND: Human metapneumovirus (hMPV) is a Paramyxovirus known to cause acute respiratory tract infections in children and young adults. To date, there is no study from the Aseer region of Saudi Arabia determining the proportion and severity of hMPV infection among pediatric hospitalized patients with respiratory infections. OBJECTIVES: The objective of this study is to determine the presence of hMPV antigens in the nasopharyngeal secretions of pediatric patients hospitalized with respiratory tract infections in the Aseer region of Saudi Arabia. MATERIALS AND METHODS: This prospective, serological hospital-based study included all pediatric patients who were admitted to Aseer Central Hospital, Abha, Saudi Arabia, from July 2016 to November 2017 with upper and/or lower respiratory tract infections. Basic demographics of patients and their clinical data on and after admission were recorded. Direct fluorescent antibody assay was used to detect the presence of hMPV antigens in the obtained nasopharyngeal secretion specimens. RESULTS: During the study, 91 pediatric patients were hospitalized due to upper and/or lower respiratory tract infections, of which 9.9% were positive for hMPV. These patients were aged 9 months to 16 years, were from Abha city or its surrounding localities and were mostly (77.8%) hospitalized during autumn or winter. The most common diagnosis on admission was bronchopneumonia (55.5%) and aspiration pneumonia (22.2%), and some patients also had underlying chronic conditions such as chronic heart disease (22.2%) and bronchial asthma (11.1%). CONCLUSIONS: The results obtained indicated that hMPV is a potential etiologic factor for the commonly occurring acute respiratory infections in hospitalized children from the Aseer region of Saudi Arabia. hMPV infection was also found to be associated with complicated respiratory conditions such as bronchopneumonia, chronic heart disease and bronchial asthma.",2019 Apr 12 May-Aug,"['Alsuheel, Ali Mohammed', 'Ali, Abdelwahid Saeed', 'Al-Hakami, Ahmed Musa', 'Shati, Ayed Abdullah', 'Chandramoorthy, Harish C.', 'Al-Qahtani, Saleh Mohammed']",Saudi J Med Med Sci,,,True
e3298846caa5271bd93b410c46b8ab6cee3eff8e,PMC,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Oman: Current Situation and Going Forward,http://dx.doi.org/10.5001/omj.2019.36,PMC6505341,31110623,CC BY-NC,,2019 May,"['Al Awaidy, Salah T.', 'Khamis, Faryal']",Oman Med J,,,True
234e0ff5a56d4d4900f17fab95a1dbbab8c3b034,PMC,WHO LAUNCHES NEW GLOBAL INFLUENZA STRATEGY,,PMC6506662,,CC BY-NC-SA,,2019,,Saudi Med J,,,False
344b7576e8d591d39fa83b3fe6d6176a61c0ec9a,PMC,Factors Influencing the Diagnosis and Treatment of Latent Tuberculosis among Contacts in Congregated Settings in Korea,http://dx.doi.org/10.3346/jkms.2019.34.e138,PMC6509364,31074252,CC BY-NC,"BACKGROUND: This study aimed to compare the indicators (the rates of diagnosis, need for treatment, treatment initiation, and treatment completion) of management of latent tuberculosis infection (LTBI) in contacts and to identify the impact of active tuberculosis (TB) index case characteristics on the exposed population in congregated settings, such as schools, workplaces, and medical institutes. METHODS: The data of 8,648 clusters in the TB epidemiological investigation database between 2013 and 2016 were extracted and analyzed to evaluate the indicators and perform multilevel logistic regression (MLR) analyses to identify the factors affecting each indicator. RESULTS: The rates of total LTBI diagnosis, need for treatment, treatment initiation, and treatment completion were 15.2%, 10.2%, 69.4%, and 76.6%, respectively. After adjusting for other factors on MLR, the probability of diagnosis and need for treatment of latent TB in contacts was higher in most types of facilities than in schools. Conversely, treatment completion rates in these facilities were lower. Notably, the correctional institutions showed the highest odds ratio (OR) relative to school for LTBI diagnosis (OR, 6.37) and need for treatment (OR, 4.49) and the lowest OR for treatment completion (OR, 0.10). CONCLUSION: This study provided evidence for the implementation of latent TB control policies in congregated settings.",2019 May 7,"['Kim, Ahreum', 'Choi, Minhyeok']",J Korean Med Sci,,,True
3831c263a7c8d673bd839bb390083c0d79003d14,PMC,Advancing Planetary Health in Australia: focus on emerging infections and antimicrobial resistance,http://dx.doi.org/10.1136/bmjgh-2018-001283,PMC6509602,31139446,CC BY-NC,"With rising population numbers, anthropogenic changes to our environment and unprecedented global connectivity, the World Economic Forum ranks the spread of infectious diseases second only to water crises in terms of potential global impact. Addressing the diverse challenges to human health and well-being in the 21st century requires an overarching focus on ‘Planetary Health’, with input from all sectors of government, non-governmental organisations, academic institutions and industry. To clarify and advance the Planetary Health agenda within Australia, specifically in relation to emerging infectious diseases (EID) and antimicrobial resistance (AMR), national experts and key stakeholders were invited to a facilitated workshop. EID themes identified included animal reservoirs, targeted surveillance, mechanisms of emergence and the role of unrecognised human vectors (the ‘invisible man’) in the spread of infection. Themes related to AMR included antimicrobial use in production and companion animals, antimicrobial stewardship, novel treatment approaches and education of professionals, politicians and the general public. Effective infection control strategies are important in both EID and AMR. We provide an overview of key discussion points, as well as important barriers identified and solutions proposed.",2019 Apr 22,"['Hill-Cawthorne, Grant', 'Negin, Joel', 'Capon, Tony', 'Gilbert, Gwendolyn L', 'Nind, Lee', 'Nunn, Michael', 'Ridgway, Patricia', 'Schipp, Mark', 'Firman, Jenny', 'Sorrell, Tania C', 'Marais, Ben J']",BMJ Glob Health,,,True
4c5c841e4ad3fbf9b31d6c0c282dfec035f716bb,PMC,The association between blood eosinophil percent and bacterial infection in acute exacerbation of chronic obstructive pulmonary disease,http://dx.doi.org/10.2147/COPD.S197361,PMC6511627,31190782,CC BY-NC,"Introduction: The use of antibiotics is based on the clinician’s experience and judgment, and antibiotics may often be overused in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Eosinophils have been studied as biomarkers of bacterial infection and prognostic factors in chronic obstructive pulmonary disease and AECOPD. Thus, the purpose of this study was to determine whether eosinophils could be used to determine bacterial infection in AECOPD events. Methods: We retrospectively analyzed the medical records of patients admitted to Korea University Guro Hospital for AECOPD between January 2011 and May 2017. Data pertaining to baseline characteristics, results of previous pulmonary function tests, treatment information during the admission period, and history of pulmonary treatment were collected before admission. Results: A total of 736 AECOPD events were eligible for inclusion and were divided into two groups based on the eosinophil count: those involving eosinophil counts of less than 2% (546 events) and those involving counts of 2% or more (190 events). In univariate analysis, the only bacterial pathogen identification events and bacterial-viral pathogen co-identification events were significantly more frequent in the group with eosinophil counts of less than 2% (P=0.010 and P=0.001, respectively). In logistic regression analysis, the rates of only bacterial pathogen identification [odds ratios =1.744; 95% confidence interval, 1.107–2.749; P=0.017] and bacterial-viral pathogen co-identification [odds ratios=2.075; 95% confidence interval, 1.081–3.984; P=0.028] were higher in the group with eosinophil count less than 2%. Conclusion: In conclusion, eosinophil counts of less than 2% are potential indicators of a bacterial infection in AECOPD events. Eosinophils could thus serve as a reference for the use of antibiotics in AECOPD treatment.",2019 May 6,"['Choi, Juwhan', 'Oh, Jee Youn', 'Lee, Young Seok', 'Hur, Gyu Young', 'Lee, Sung Yong', 'Shim, Jae Jeong', 'Kang, Kyung Ho', 'Min, Kyung Hoon']",Int J Chron Obstruct Pulmon Dis,,,True
4a8c5f46f5d234453c3c498a85a2ffb261e584c4,PMC,"Virologic study of acute lower respiratory tract infections in children admitted to the paediatric department of Blida University Hospital, Algeria",http://dx.doi.org/10.1016/j.nmni.2019.100536,PMC6517316,31193119,CC BY-NC-ND,"Acute lower respiratory tract infections (ALRTI) such as pneumonia and bronchiolitis are major causes of mortality and morbidity in children under 5 years of age. The main microbial agents responsible for ALRTI are either bacterial agents (Streptococcus pneumoniae, Haemophilus influenzae type b, Mycoplasma pneumoniae) or viruses (respiratory syncytial virus (RSV, also known as human orthopneumovirus), Myxovirus influenzae, Myxovirus parainfluenzae, adenovirus) [1]. More recently, other viruses (rhinovirus, metapneumovirus, coronavirus, bocavirus) have been implicated in ALRTI; their identification has been facilitated by new molecular biology techniques such as real-time PCR. To our knowledge, these emerging viruses have never been the subject of epidemiologic studies in our country.",2019 Mar 27,"['Derrar, F.', 'Izri, K.', 'Kaddache, C.', 'Boukari, R.', 'Hannoun, D.']",New Microbes New Infect,,,False
26360be96ced1f242e01966b0d152c32544f3d60,PMC,Extension of the known distribution of a novel clade C betacoronavirus in a wildlife host,http://dx.doi.org/10.1017/S0950268819000207,PMC6518468,31063092,CC BY-NC-ND,"Disease surveillance in wildlife populations presents a logistical challenge, yet is critical in gaining a deeper understanding of the presence and impact of wildlife pathogens. Erinaceus coronavirus (EriCoV), a clade C Betacoronavirus, was first described in Western European hedgehogs (Erinaceus europaeus) in Germany. Here, our objective was to determine whether EriCoV is present, and if it is associated with disease, in Great Britain (GB). An EriCoV-specific BRYT-Green(®) real-time reverse transcription PCR assay was used to test 351 samples of faeces or distal large intestinal tract contents collected from casualty or dead hedgehogs from a wide area across GB. Viral RNA was detected in 10.8% (38) samples; however, the virus was not detected in any of the 61 samples tested from Scotland. The full genome sequence of the British EriCoV strain was determined using next generation sequencing; it shared 94% identity with a German EriCoV sequence. Multivariate statistical models using hedgehog case history data, faecal specimen descriptions and post-mortem examination findings found no significant associations indicative of disease associated with EriCoV in hedgehogs. These findings indicate that the Western European hedgehog is a reservoir host of EriCoV in the absence of apparent disease.",2019 Apr 3,"['Saldanha, I. F.', 'Lawson, B.', 'Goharriz, H.', 'Rodriguez-Ramos Fernandez, J.', 'John, S. K.', 'Fooks, A. R.', 'Cunningham, A. A.', 'Johnson, N.', 'Horton, D. L.']",Epidemiol Infect,,,True
b03c7f6241f74f5934ebec0287004bf9ff784922,PMC,Association between rs12252 and influenza susceptibility and severity: an updated meta-analysis,http://dx.doi.org/10.1017/S0950268818002832,PMC6518565,30421689,CC BY-NC-SA,"In several lately published studies, the association between single-nucleotide polymorphism (SNP, rs12252) of IFITM3 and the risk of influenza is inconsistent. To further understand the association between the SNP of IFITM3 and the risk of influenza, we searched related studies in five databases including PubMed published earlier than 9 November 2017. Ten sets of data from nine studies were included and data were analysed by Revman 5.0 and Stata 12.0 in our updated meta-analysis, which represented 1365 patients and 5425 no-influenza controls from four different ethnicities. Here strong association between rs12252 and influenza was found in all four genetic models. The significant differences in the allelic model (C vs. T: odds ratio (OR) = 1.35, 95% confidence interval (CI) (1.03–1.79), P = 0.03) and homozygote model (CC vs. TT: OR = 10.63, 95% CI (3.39–33.33), P < 0.00001) in the Caucasian subgroup were discovered, which is very novel and striking. Also novel discoveries were found in the allelic model (C vs. T: OR = 1.37, 95% CI (1.08–1.73), P = 0.009), dominant model (CC + CT vs. TT: OR = 1.48, 95% CI (1.08–2.02), P = 0.01) and homozygote model (CC vs. TT: OR = 2.84, 95% CI (1.36–5.92), P = 0.005) when we compared patients with mild influenza with healthy individuals. Our meta-analysis suggests that single-nucleotide T to C polymorphism of IFITM3 associated with increasingly risk of severe and mild influenza in both Asian and Caucasian populations.",2018 Nov 13,"['Chen, T.', 'Xiao, M.', 'Yang, J.', 'Chen, Y. K.', 'Bai, T.', 'Tang, X. J.', 'Shu, Y. L.']",Epidemiol Infect,,,True
e1d7c0ed2db49bcc8e49814b1bb24bd01f9ba8c4,PMC,Potential use of Pichia pastoris strain SMD1168H expressing DNA topoisomerase I in the screening of potential anti-breast cancer agents,http://dx.doi.org/10.3892/mmr.2019.10201,PMC6522884,31059050,CC BY-NC-ND,"Cancer chemotherapy possesses high toxicity, particularly when a higher concentration of drugs is administered to patients. Therefore, searching for more effective compounds to reduce the toxicity of treatments, while still producing similar effects as current chemotherapy regimens, is required. Currently, the search for potential anticancer agents involves a random, inaccurate process with strategic deficits and a lack of specific targets. For this reason, the initial in vitro high-throughput steps in the screening process should be reviewed for rapid identification of the compounds that may serve as anticancer agents. The present study aimed to investigate the potential use of the Pichia pastoris strain SMD1168H expressing DNA topoisomerase I (SMD1168H-TOPOI) in a yeast-based assay for screening potential anticancer agents. The cell density that indicated the growth of the recombinant yeast without treatment was first measured by spectrophotometry. Subsequently, the effects of glutamate (agonist) and camptothecin (antagonist) on the recombinant yeast cell density were investigated using the same approach, and finally, the effect of camptothecin on various cell lines was determined and compared with its effect on recombinant yeast. The current study demonstrated that growth was enhanced in SMD1168H-TOPOI as compared with that in SMD1168H. Glutamate also enhanced the growth of the SMD1168H; however, the growth effect was not enhanced in SMD1168H-TOPOI treated with glutamate. By contrast, camptothecin caused only lower cell density and growth throughout the treatment of SMD1168H-TOPOI. The findings of the current study indicated that SMD1168H-TOPOI has similar characteristics to MDA-MB-231 cells; therefore, it can be used in a yeast-based assay to screen for more effective compounds that may inhibit the growth of highly metastatic breast cancer cells.",2019 Jun 30,"['Xin, Jian', 'Mahtar, Wan Nor Azlin Wan', 'Siah, Poh Chiew', 'Miswan, Noorizan', 'Khoo, Boon Yin']",Mol Med Rep,,,True
ca274e20fd535ce3666baf7a70daffcecd68d5ae,PMC,Deleted in colorectal cancer (netrin‐1 receptor) antibodies and limbic encephalitis in a cat with hippocampal necrosis,http://dx.doi.org/10.1111/jvim.15492,PMC6524083,30942925,CC BY-NC,"A 7‐year‐old neutered female domestic shorthaired cat born in Poland and then moved to Japan presented to the local clinic with recent onset of convulsive cluster seizures and status epilepticus. Magnetic resonance imaging revealed bilateral swelling of the hippocampus with T2 hyperintensity and contrast enhancing image, suggesting hippocampal necrosis. The cat completely recovered after treatment with antiepileptic drugs (AED) and administration of prednisolone (1 mg/kg PO q24h for 4 days and tapered). However, cluster seizures reoccurred and developed into status epilepticus despite increasing doses of AED. Although the convulsions were resolved by other AEDs, stupor and renal failure developed, and the cat was euthanized. Pathological findings were consistent with hippocampal necrosis. Immunological analysis for leucine‐rich glioma inactivated 1 (LGI1) autoantibodies was negative, but antibodies against DCC (deleted in colorectal carcinoma) known as netrin‐1 receptor were found. This report describes a case of feline autoimmune limbic encephalitis and hippocampal necrosis that were presumably associated with DCC autoantibodies.",2019 Apr 3 May-Jun,"['Hasegawa, Daisuke', 'Ohnishi, Yumi', 'Koyama, Eiji', 'Matsunaga, Satoru', 'Ohtani, Shouhei', 'Nakanishi, Akio', 'Shiga, Takanori', 'Chambers, James K.', 'Uchida, Kazuyuki', 'Yokoi, Norihiko', 'Fukata, Yuko', 'Fukata, Masaki']",J Vet Intern Med,,,True
d7edc599de4625ef946fca148a7e7138d529eb5d,PMC,Deleted in colorectal cancer (netrin‐1 receptor) antibodies and limbic encephalitis in a cat with hippocampal necrosis,http://dx.doi.org/10.1111/jvim.15492,PMC6524083,30942925,CC BY-NC,"A 7‐year‐old neutered female domestic shorthaired cat born in Poland and then moved to Japan presented to the local clinic with recent onset of convulsive cluster seizures and status epilepticus. Magnetic resonance imaging revealed bilateral swelling of the hippocampus with T2 hyperintensity and contrast enhancing image, suggesting hippocampal necrosis. The cat completely recovered after treatment with antiepileptic drugs (AED) and administration of prednisolone (1 mg/kg PO q24h for 4 days and tapered). However, cluster seizures reoccurred and developed into status epilepticus despite increasing doses of AED. Although the convulsions were resolved by other AEDs, stupor and renal failure developed, and the cat was euthanized. Pathological findings were consistent with hippocampal necrosis. Immunological analysis for leucine‐rich glioma inactivated 1 (LGI1) autoantibodies was negative, but antibodies against DCC (deleted in colorectal carcinoma) known as netrin‐1 receptor were found. This report describes a case of feline autoimmune limbic encephalitis and hippocampal necrosis that were presumably associated with DCC autoantibodies.",2019 Apr 3 May-Jun,"['Hasegawa, Daisuke', 'Ohnishi, Yumi', 'Koyama, Eiji', 'Matsunaga, Satoru', 'Ohtani, Shouhei', 'Nakanishi, Akio', 'Shiga, Takanori', 'Chambers, James K.', 'Uchida, Kazuyuki', 'Yokoi, Norihiko', 'Fukata, Yuko', 'Fukata, Masaki']",J Vet Intern Med,,,False
543ac2431685616436dfe9f7ff063a02a741686f,PMC,"Efficacy of an orally administered anti‐diarrheal probiotic paste (Pro‐Kolin Advanced) in dogs with acute diarrhea: A randomized, placebo‐controlled, double‐blinded clinical study",http://dx.doi.org/10.1111/jvim.15481,PMC6524086,30882953,CC BY-NC,"BACKGROUND: Acute diarrhea is a common clinical presentation of dogs. The effect of specific anti‐diarrheal probiotic pastes (ADPPs) in the management of acute, uncomplicated diarrhea in dogs is unknown. HYPOTHESIS: Administration of an ADPP containing Enterococcus faecium 4b1707 will improve the clinical outcome of acute, uncomplicated diarrhea in dogs compared to placebo. ANIMALS: One hundred forty‐eight client‐owned dogs with acute diarrhea as the main clinical sign. METHODS: Double‐blinded, placebo‐controlled, randomized, blocked, multicenter clinical field study conducted at 14 primary care veterinary practices in the United Kingdom and Ireland. RESULTS: The ADPP was associated with better clinical outcome compared to placebo in dogs with acute, uncomplicated diarrhea. Dogs in the ADPP group had a significantly shorter duration of diarrhea (ADPP: median, 32 hours; 95% confidence interval [CI], 2‐118; n = 51; Placebo: median, 47 hours; 95% CI, 4‐167; n = 58; P = .008) and the rate of resolution of diarrhea was 1.60 times faster in the ADPP group than in the Placebo group (ratio, 1.60; 95% CI, 1.08‐2.44; P = .02). Fewer dogs required additional medical intervention (AMI) for non‐improvement or worsening in the ADPP group compared to the Placebo group (3.5% of dogs and 14.8% of dogs, respectively), with a relative risk of 0.88 (P = .04; AMI, ADPP, 3.5%, 2/57 dogs; Placebo, 14.8%, 9/61 dogs; relative risk, 0.88; 95% CI, 0.77‐0.99). CONCLUSION AND CLINICAL IMPORTANCE: The ADPP may accelerate resolution of acute diarrhea in dogs and decrease the requirement for AMI.",2019 Mar 18 May-Jun,"['Nixon, Sophie L.', 'Rose, Lindsay', 'Muller, Annika T.']",J Vet Intern Med,,,True
fedbb043730105d05937dcf351201e597fc0e8bb,PMC,"Efficacy of an orally administered anti‐diarrheal probiotic paste (Pro‐Kolin Advanced) in dogs with acute diarrhea: A randomized, placebo‐controlled, double‐blinded clinical study",http://dx.doi.org/10.1111/jvim.15481,PMC6524086,30882953,CC BY-NC,"BACKGROUND: Acute diarrhea is a common clinical presentation of dogs. The effect of specific anti‐diarrheal probiotic pastes (ADPPs) in the management of acute, uncomplicated diarrhea in dogs is unknown. HYPOTHESIS: Administration of an ADPP containing Enterococcus faecium 4b1707 will improve the clinical outcome of acute, uncomplicated diarrhea in dogs compared to placebo. ANIMALS: One hundred forty‐eight client‐owned dogs with acute diarrhea as the main clinical sign. METHODS: Double‐blinded, placebo‐controlled, randomized, blocked, multicenter clinical field study conducted at 14 primary care veterinary practices in the United Kingdom and Ireland. RESULTS: The ADPP was associated with better clinical outcome compared to placebo in dogs with acute, uncomplicated diarrhea. Dogs in the ADPP group had a significantly shorter duration of diarrhea (ADPP: median, 32 hours; 95% confidence interval [CI], 2‐118; n = 51; Placebo: median, 47 hours; 95% CI, 4‐167; n = 58; P = .008) and the rate of resolution of diarrhea was 1.60 times faster in the ADPP group than in the Placebo group (ratio, 1.60; 95% CI, 1.08‐2.44; P = .02). Fewer dogs required additional medical intervention (AMI) for non‐improvement or worsening in the ADPP group compared to the Placebo group (3.5% of dogs and 14.8% of dogs, respectively), with a relative risk of 0.88 (P = .04; AMI, ADPP, 3.5%, 2/57 dogs; Placebo, 14.8%, 9/61 dogs; relative risk, 0.88; 95% CI, 0.77‐0.99). CONCLUSION AND CLINICAL IMPORTANCE: The ADPP may accelerate resolution of acute diarrhea in dogs and decrease the requirement for AMI.",2019 Mar 18 May-Jun,"['Nixon, Sophie L.', 'Rose, Lindsay', 'Muller, Annika T.']",J Vet Intern Med,,,False
79e75fc82b515edcb68d6c8a6b83d630e3b21193,PMC,Perspectives in veterinary medicine: Description and classification of bronchiolar disorders in cats,http://dx.doi.org/10.1111/jvim.15473,PMC6524100,30982233,CC BY-NC,"This Perspectives in Veterinary Medicine article seeks to define, describe putative causes, and discuss key diagnostic tests for primary and secondary bronchiolar disorders to propose a classification scheme in cats with support from a literature review and case examples. The small airways (bronchioles with inner diameters <2 mm), located at the transitional zone between larger conducting airways and the pulmonary acinus, have been overlooked as major contributors to clinical syndromes of respiratory disease in cats. Because the trigger for many bronchiolar disorders is environmental and humans live in a shared environment with similar susceptibility, understanding these diseases in pet cats has relevance to One Health. Thoracic radiography, the major imaging modality used in the diagnostic evaluation of respiratory disease in cats, has low utility in detection of bronchiolar disease. Computed tomography (CT) with paired inspiratory and expiratory scans can detect pathology centered on small airways. In humans, treatment of bronchiolar disorders is not well established because of heterogeneous presentations and often late definitive diagnosis. A review of the human and veterinary medical literature will serve as the basis for a proposed classification scheme in cats. A case series of cats with CT or histopathologic evidence of bronchiolar lesions or both, either as a primary disorder or secondary to extension from large airway disease or interstitial lung disease, will be presented. Future multi‐institutional and multidisciplinary discussions among clinicians, radiologists, and pathologists will help refine and develop this classification scheme to promote early and specific recognition and optimize treatment.",2019 Apr 13 May-Jun,"['Reinero, Carol R.', 'Masseau, Isabelle', 'Grobman, Megan', 'Vientos‐Plotts, Aida', 'Williams, Kurt']",J Vet Intern Med,,,True
239cef1150ea526ebe6c454413ce4283b36463da,PMC,Perspectives in veterinary medicine: Description and classification of bronchiolar disorders in cats,http://dx.doi.org/10.1111/jvim.15473,PMC6524100,30982233,CC BY-NC,"This Perspectives in Veterinary Medicine article seeks to define, describe putative causes, and discuss key diagnostic tests for primary and secondary bronchiolar disorders to propose a classification scheme in cats with support from a literature review and case examples. The small airways (bronchioles with inner diameters <2 mm), located at the transitional zone between larger conducting airways and the pulmonary acinus, have been overlooked as major contributors to clinical syndromes of respiratory disease in cats. Because the trigger for many bronchiolar disorders is environmental and humans live in a shared environment with similar susceptibility, understanding these diseases in pet cats has relevance to One Health. Thoracic radiography, the major imaging modality used in the diagnostic evaluation of respiratory disease in cats, has low utility in detection of bronchiolar disease. Computed tomography (CT) with paired inspiratory and expiratory scans can detect pathology centered on small airways. In humans, treatment of bronchiolar disorders is not well established because of heterogeneous presentations and often late definitive diagnosis. A review of the human and veterinary medical literature will serve as the basis for a proposed classification scheme in cats. A case series of cats with CT or histopathologic evidence of bronchiolar lesions or both, either as a primary disorder or secondary to extension from large airway disease or interstitial lung disease, will be presented. Future multi‐institutional and multidisciplinary discussions among clinicians, radiologists, and pathologists will help refine and develop this classification scheme to promote early and specific recognition and optimize treatment.",2019 Apr 13 May-Jun,"['Reinero, Carol R.', 'Masseau, Isabelle', 'Grobman, Megan', 'Vientos‐Plotts, Aida', 'Williams, Kurt']",J Vet Intern Med,,,False
98ecc13f4c66ae6de60d2e2ffdee5835a3b9dfd7,PMC,Perspectives in veterinary medicine: Description and classification of bronchiolar disorders in cats,http://dx.doi.org/10.1111/jvim.15473,PMC6524100,30982233,CC BY-NC,"This Perspectives in Veterinary Medicine article seeks to define, describe putative causes, and discuss key diagnostic tests for primary and secondary bronchiolar disorders to propose a classification scheme in cats with support from a literature review and case examples. The small airways (bronchioles with inner diameters <2 mm), located at the transitional zone between larger conducting airways and the pulmonary acinus, have been overlooked as major contributors to clinical syndromes of respiratory disease in cats. Because the trigger for many bronchiolar disorders is environmental and humans live in a shared environment with similar susceptibility, understanding these diseases in pet cats has relevance to One Health. Thoracic radiography, the major imaging modality used in the diagnostic evaluation of respiratory disease in cats, has low utility in detection of bronchiolar disease. Computed tomography (CT) with paired inspiratory and expiratory scans can detect pathology centered on small airways. In humans, treatment of bronchiolar disorders is not well established because of heterogeneous presentations and often late definitive diagnosis. A review of the human and veterinary medical literature will serve as the basis for a proposed classification scheme in cats. A case series of cats with CT or histopathologic evidence of bronchiolar lesions or both, either as a primary disorder or secondary to extension from large airway disease or interstitial lung disease, will be presented. Future multi‐institutional and multidisciplinary discussions among clinicians, radiologists, and pathologists will help refine and develop this classification scheme to promote early and specific recognition and optimize treatment.",2019 Apr 13 May-Jun,"['Reinero, Carol R.', 'Masseau, Isabelle', 'Grobman, Megan', 'Vientos‐Plotts, Aida', 'Williams, Kurt']",J Vet Intern Med,,,False
13b16688b86661a6165f9c688c4f45893b7e47c5,PMC,Human LAP(+)GARP(+)FOXP3(+) regulatory T cells attenuate xenogeneic graft versus host disease,http://dx.doi.org/10.7150/thno.30254,PMC6531299,31149046,CC BY-NC,"Adoptive transfer of regulatory T cells (FOXP3(+) Tregs) has been developed as a potential curative immune therapy to prevent and treat autoimmune and graft-versus-host diseases (GVHD). A major limitation that has hindered the use of Treg immunotherapy in humans is the difficulty of consistently isolating and obtaining highly purified Tregs after ex vivo expansion. Methods: We isolated bona fide Tregs from expansion cultures based on their selective surface expression of latency-associated peptide (LAP). The TCR Vβ diversity and intracellular cytokine production of Tregs were determined by flow cytometer. The TSDR methylation was determined by epigenetic human FOXP3 qPCR Assay. Their in vitro and in vivo potency was confirmed with suppression assay and humanized xenogeneic GVHD (xGVHD) murine model, respectively. Results: LAP(+) repurification results in >90% LAP(+)FOXP3(+) Tregs, leaving behind FOXP3(-) and FOXP3(+) nonTregs within the LAP(-) population. After 4-week expansion, the LAP(+) Tregs were >1 billion cells, highly suppressive and anergic in vitro, >90% demethylated in the TSDR and able to maintain TCR Vβ diversity. In the xGVHD model, exogenous CD25(-)PBMC administered alone results in a median survival of 32 days. The co-transfer of LAP(+) Tregs increased median survival to 47 days, while the LAP parent (CD25(+)) and LAP(-) nonTregs had median survival of 39 and 31 days, respectively. Conclusions: These preclinical data together provide evidence that LAP(+) Tregs are highly purified with fully suppressive function for cell therapy. This population results in a more effective and safer product for immunotherapy to treat GVHD and provides the necessary preclinical data for transition into a clinical trial with LAP(+) Tregs to prevent or treat GVHD and other autoimmune diseases.",2019 Apr 12,"['Wang, Huihui', 'Song, Hyo', 'Pham, Anha V.', 'Cooper, Laurence J.', 'Schulze, Janika J.', 'Olek, Sven', 'Tran, Dat Q.']",Theranostics,,,True
a5eccd2676bf90cf3697384f0cfa0ba0056a6c5e,PMC,Human LAP(+)GARP(+)FOXP3(+) regulatory T cells attenuate xenogeneic graft versus host disease,http://dx.doi.org/10.7150/thno.30254,PMC6531299,31149046,CC BY-NC,"Adoptive transfer of regulatory T cells (FOXP3(+) Tregs) has been developed as a potential curative immune therapy to prevent and treat autoimmune and graft-versus-host diseases (GVHD). A major limitation that has hindered the use of Treg immunotherapy in humans is the difficulty of consistently isolating and obtaining highly purified Tregs after ex vivo expansion. Methods: We isolated bona fide Tregs from expansion cultures based on their selective surface expression of latency-associated peptide (LAP). The TCR Vβ diversity and intracellular cytokine production of Tregs were determined by flow cytometer. The TSDR methylation was determined by epigenetic human FOXP3 qPCR Assay. Their in vitro and in vivo potency was confirmed with suppression assay and humanized xenogeneic GVHD (xGVHD) murine model, respectively. Results: LAP(+) repurification results in >90% LAP(+)FOXP3(+) Tregs, leaving behind FOXP3(-) and FOXP3(+) nonTregs within the LAP(-) population. After 4-week expansion, the LAP(+) Tregs were >1 billion cells, highly suppressive and anergic in vitro, >90% demethylated in the TSDR and able to maintain TCR Vβ diversity. In the xGVHD model, exogenous CD25(-)PBMC administered alone results in a median survival of 32 days. The co-transfer of LAP(+) Tregs increased median survival to 47 days, while the LAP parent (CD25(+)) and LAP(-) nonTregs had median survival of 39 and 31 days, respectively. Conclusions: These preclinical data together provide evidence that LAP(+) Tregs are highly purified with fully suppressive function for cell therapy. This population results in a more effective and safer product for immunotherapy to treat GVHD and provides the necessary preclinical data for transition into a clinical trial with LAP(+) Tregs to prevent or treat GVHD and other autoimmune diseases.",2019 Apr 12,"['Wang, Huihui', 'Song, Hyo', 'Pham, Anha V.', 'Cooper, Laurence J.', 'Schulze, Janika J.', 'Olek, Sven', 'Tran, Dat Q.']",Theranostics,,,False
de3e0083918cb84a1b2df214b7cd898afbe12206,PMC,"Characterization of G-Quadruplex Motifs in espB, espK, and cyp51 Genes of Mycobacterium tuberculosis as Potential Drug Targets",http://dx.doi.org/10.1016/j.omtn.2019.04.022,PMC6531831,31128421,CC BY-NC-ND,"G-quadruplex structure forming motifs are among the most studied evolutionarily conserved drug targets that are present throughout the genome of different organisms and susceptible to influencing various biological processes. Here we report highly conserved potential G-quadruplex motifs (PGQs) in three essential genes (espK, espB, and cyp51) among 160 strains of the Mycobacterium tuberculosis genome. Products of these genes are involved in pathways that are responsible for virulence determination of bacteria inside the host cell and its survival by maintaining membrane fluidity. The espK and espB genes are essential players that prevent the formation of mature phagolysosome and antigen presentation by host macrophages. The cyp51 is another PGQ-possessing gene involved in sterol biosynthesis pathway and membrane formation. In the present study, we revealed the formation of stable intramolecular parallel G-quadruplex structures by Mycobacterium PGQs using a combination of techniques (NMR, circular dichroism [CD], and gel electrophoresis). Next, isothermal titration calorimetry (ITC) and CD melting analysis demonstrated that a well-known G-quadruplex ligand, TMPyP4, binds to and stabilizes these PGQ motifs. Finally, polymerase inhibition and qRT-PCR assays highlight the biological relevance of PGQ-possessing genes in this pathogen and demonstrate that G-quadruplexes are potential drug targets for the development of effective anti-tuberculosis therapeutics.",2019 Apr 30,"['Mishra, Subodh Kumar', 'Shankar, Uma', 'Jain, Neha', 'Sikri, Kriti', 'Tyagi, Jaya Sivaswami', 'Sharma, Tarun Kumar', 'Mergny, Jean-Louis', 'Kumar, Amit']",Mol Ther Nucleic Acids,,,False
4691859fba97c59b688292d6d2132d3ef1510e3a,PMC,"Characterization of G-Quadruplex Motifs in espB, espK, and cyp51 Genes of Mycobacterium tuberculosis as Potential Drug Targets",http://dx.doi.org/10.1016/j.omtn.2019.04.022,PMC6531831,31128421,CC BY-NC-ND,"G-quadruplex structure forming motifs are among the most studied evolutionarily conserved drug targets that are present throughout the genome of different organisms and susceptible to influencing various biological processes. Here we report highly conserved potential G-quadruplex motifs (PGQs) in three essential genes (espK, espB, and cyp51) among 160 strains of the Mycobacterium tuberculosis genome. Products of these genes are involved in pathways that are responsible for virulence determination of bacteria inside the host cell and its survival by maintaining membrane fluidity. The espK and espB genes are essential players that prevent the formation of mature phagolysosome and antigen presentation by host macrophages. The cyp51 is another PGQ-possessing gene involved in sterol biosynthesis pathway and membrane formation. In the present study, we revealed the formation of stable intramolecular parallel G-quadruplex structures by Mycobacterium PGQs using a combination of techniques (NMR, circular dichroism [CD], and gel electrophoresis). Next, isothermal titration calorimetry (ITC) and CD melting analysis demonstrated that a well-known G-quadruplex ligand, TMPyP4, binds to and stabilizes these PGQ motifs. Finally, polymerase inhibition and qRT-PCR assays highlight the biological relevance of PGQ-possessing genes in this pathogen and demonstrate that G-quadruplexes are potential drug targets for the development of effective anti-tuberculosis therapeutics.",2019 Apr 30,"['Mishra, Subodh Kumar', 'Shankar, Uma', 'Jain, Neha', 'Sikri, Kriti', 'Tyagi, Jaya Sivaswami', 'Sharma, Tarun Kumar', 'Mergny, Jean-Louis', 'Kumar, Amit']",Mol Ther Nucleic Acids,,,False
f4998df4f550be136b50f7d4d6234e2cf916b583,PMC,"Characterization of G-Quadruplex Motifs in espB, espK, and cyp51 Genes of Mycobacterium tuberculosis as Potential Drug Targets",http://dx.doi.org/10.1016/j.omtn.2019.04.022,PMC6531831,31128421,CC BY-NC-ND,"G-quadruplex structure forming motifs are among the most studied evolutionarily conserved drug targets that are present throughout the genome of different organisms and susceptible to influencing various biological processes. Here we report highly conserved potential G-quadruplex motifs (PGQs) in three essential genes (espK, espB, and cyp51) among 160 strains of the Mycobacterium tuberculosis genome. Products of these genes are involved in pathways that are responsible for virulence determination of bacteria inside the host cell and its survival by maintaining membrane fluidity. The espK and espB genes are essential players that prevent the formation of mature phagolysosome and antigen presentation by host macrophages. The cyp51 is another PGQ-possessing gene involved in sterol biosynthesis pathway and membrane formation. In the present study, we revealed the formation of stable intramolecular parallel G-quadruplex structures by Mycobacterium PGQs using a combination of techniques (NMR, circular dichroism [CD], and gel electrophoresis). Next, isothermal titration calorimetry (ITC) and CD melting analysis demonstrated that a well-known G-quadruplex ligand, TMPyP4, binds to and stabilizes these PGQ motifs. Finally, polymerase inhibition and qRT-PCR assays highlight the biological relevance of PGQ-possessing genes in this pathogen and demonstrate that G-quadruplexes are potential drug targets for the development of effective anti-tuberculosis therapeutics.",2019 Apr 30,"['Mishra, Subodh Kumar', 'Shankar, Uma', 'Jain, Neha', 'Sikri, Kriti', 'Tyagi, Jaya Sivaswami', 'Sharma, Tarun Kumar', 'Mergny, Jean-Louis', 'Kumar, Amit']",Mol Ther Nucleic Acids,,,True
81cfdc6601a05ba9db405a714d3372ea328a2186,PMC,Evidence for Cross-Protection Against Subsequent Febrile Respiratory Illness Episodes From Prior Infections by Different Viruses Among Singapore Military Recruits 2009–2014,http://dx.doi.org/10.1093/infdis/jiz046,PMC6534195,30722024,CC BY-NC-ND,"BACKGROUND: Few studies have evaluated the relative cross-protection conferred by infection with different groups of viruses through studies of sequential infections in humans. We investigated the presence of short-lived relative cross-protection conferred by specific prior viral infections against subsequent febrile respiratory illness (FRI). METHODS: Men enlisted in basic military training between December 2009 and December 2014 were recruited, with the first FRI as the study entry point. ResPlex II assays and real-time polymerase chain reaction assays were used to detect viral pathogens in nasal wash samples, and survival analyses were performed to determine whether infection with particular viruses conferred short-lived relative cross-protection against FRI. RESULTS: Prior infection with adenovirus (hazard ratio [HR], 0.24; 95% confidence interval [CI], .14–.44) or influenza virus (HR, 0.52; 95% CI, .38–.73) conferred relative protection against subsequent FRI episode. Results were statistically significant even after adjustment for the interval between enlistment and FRI (P < .001). Adenovirus-positive participants with FRI episodes tended to be protected against subsequent infection with adenovirus, coronavirus, enterovirus/rhinovirus, and influenza virus (P = .062–.093), while men with influenza virus–positive FRI episodes tended be protected against subsequent infection with adenovirus (P = .044) and influenza virus (P = .081). CONCLUSION: Prior adenovirus or influenza virus infection conferred cross-protection against subsequent FRI episodes relative to prior infection due to other circulating viruses.",2019 Jun 15,"['Chen, I-Cheng Mark', 'Loh, Jin Phang', 'Chuah, Cheryl X P', 'Gao, Qiu Han Christine', 'Sun, Yinxiaohe', 'Ng, Sock Hoon', 'Koh, Wee-Hong Victor', 'Goh, Ee Hui', 'Zhao, Xiahong', 'Tambyah, Paul Anantharajah', 'Cook, Alex R', 'Chng, Jeremiah', 'Pang, Junxiong', 'Tan, Boon-Huan', 'Lee, Vernon J']",J Infect Dis,,,True
e2b26fb1febcce2de00f4e178958e710cf468416,PMC,Development of a fluorescent loop-mediated isothermal amplification assay for rapid and simple diagnosis of bovine leukemia virus infection,http://dx.doi.org/10.1292/jvms.19-0009,PMC6541838,30918136,CC BY-NC-ND,"Bovine leukemia virus (BLV) causes enzootic bovine leukosis (EBL), a condition that threatens the sustainability of the livestock industry. A fluorescent loop-mediated isothermal amplification (fLAMP) assay targeting BLV env sequences was developed and used to evaluate 100 bovine blood samples. Compared with a conventional real-time PCR (rPCR) assay, the fLAMP assay achieved 87.3% (62/71) sensitivity and 100% (29/29) specificity. The rPCR assay took 65 min, while the fLAMP assay took 8 min to 30 min from the beginning of DNA amplification to final judgement with a comparable limit of detection. The fLAMP is a potential tool for the rapid and simple diagnosis of BLV infection to supplement ELISA testing and can be used by local laboratories and slaughterhouses without special equipment.",2019 May 27,"['NAGAO, Konomu', 'MAKINO, Ryohei', 'APEGO, Francis Victor', 'MEKATA, Hirohisa', 'YAMAZAKI, Wataru']",J Vet Med Sci,,,True
26b7be83c700658a9d095fc1fa44533136e9eadc,PMC,Development of a fluorescent loop-mediated isothermal amplification assay for rapid and simple diagnosis of bovine leukemia virus infection,http://dx.doi.org/10.1292/jvms.19-0009,PMC6541838,30918136,CC BY-NC-ND,"Bovine leukemia virus (BLV) causes enzootic bovine leukosis (EBL), a condition that threatens the sustainability of the livestock industry. A fluorescent loop-mediated isothermal amplification (fLAMP) assay targeting BLV env sequences was developed and used to evaluate 100 bovine blood samples. Compared with a conventional real-time PCR (rPCR) assay, the fLAMP assay achieved 87.3% (62/71) sensitivity and 100% (29/29) specificity. The rPCR assay took 65 min, while the fLAMP assay took 8 min to 30 min from the beginning of DNA amplification to final judgement with a comparable limit of detection. The fLAMP is a potential tool for the rapid and simple diagnosis of BLV infection to supplement ELISA testing and can be used by local laboratories and slaughterhouses without special equipment.",2019 May 27,"['NAGAO, Konomu', 'MAKINO, Ryohei', 'APEGO, Francis Victor', 'MEKATA, Hirohisa', 'YAMAZAKI, Wataru']",J Vet Med Sci,,,False
30fd1c06ba7ba3777ee5a348dfc0ee8343f4fdb2,PMC,"Severe Acute Respiratory Infections With Influenza and Noninfluenza Respiratory Viruses: Yemen, 2011-2016",http://dx.doi.org/10.1177/0046958019850731,PMC6542124,31137990,CC BY-NC,"In 2010, Yemen started the surveillance for severe acute respiratory infections (SARIs) by establishing 2 sentinel sites in Sana’a and Aden city. This study aims to determine the proportions of influenza and noninfluenza viruses among SARI patients and to determine the severity of SARI and its associated factors. The data of SARI patients who were admitted to SARI surveillance sites at Al Johory hospital in Sana’a and Al Wahdah hospital in Aden city during the period 2011-2016 were analyzed. The proportions of positive influenza viruses (type A, B) and noninfluenza viruses (respiratory syncytial, adenovirus, human parainfluenza, and human metapneumovirus), intensive care unit (ICU) admission rate, and fatality rate among SARI patients were calculated. A total of 1811 of SARI patients were admitted during 2011-2016. Of those, 78% were <15 years old. A total of 89 (5%) patients had influenza viruses and 655 (36%) had noninfluenza viruses. The overall ICU admission rate was 40% and the case-fatality rate was 8%. Infection by influenza type (A, B) and mixed (adenovirus, human parainfluenza) was significantly associated with lower ICU admission. Age <15 years old, infection with influenza B, pre-existence of chronic diseases, and admission to Aden site were significantly associated with higher fatality rate among patients. In conclusion; SARI patients in Yemen had a high ICU admission and case-fatality rates. Influenza type B, chronic diseases, and admission to Aden site are associated with higher fatality rate. Expanding surveillance sites and panel of laboratory tests to involve other pathogens will help to provide accurate diagnosis for SARI etiology and give more comprehensive picture. Training staff for SARI case management will help to reduce severe outcomes.",2019 May 29,"['Al Amad, Mohammad Abdullah', 'Al Mahaqri, Ali Ali', 'Al Serouri, Abdulwahed Abdulgabar', 'Khader, Yousef S.']",Inquiry,,,True
ed610e3cb3696b2a25490d26ad19a1ef8229663d,PMC,Modulation of HIV-1 Gag/Gag-Pol frameshifting by tRNA abundance,http://dx.doi.org/10.1093/nar/gkz202,PMC6547452,30968122,CC BY-NC,"A hallmark of translation in human immunodeficiency virus type 1 (HIV-1) is a –1 programmed ribosome frameshifting event that produces the Gag-Pol fusion polyprotein. The constant Gag to Gag-Pol ratio is essential for the virion structure and infectivity. Here we show that the frameshifting efficiency is modulated by Leu-tRNA(Leu) that reads the UUA codon at the mRNA slippery site. This tRNA(Leu) isoacceptor is particularly rare in human cell lines derived from T-lymphocytes, the cells that are targeted by HIV-1. When UUA decoding is delayed, the frameshifting follows an alternative route, which maintains the Gag to Gag-Pol ratio constant. A second potential slippery site downstream of the first one is normally inefficient but can also support –1-frameshifting when altered by a compensatory resistance mutation in response to current antiviral drug therapy. Together these different regimes allow the virus to maintain a constant –1-frameshifting efficiency to ensure successful virus propagation.",2019 Jun 4,"['Korniy, Natalia', 'Goyal, Akanksha', 'Hoffmann, Markus', 'Samatova, Ekaterina', 'Peske, Frank', 'Pöhlmann, Stefan', 'Rodnina, Marina V']",Nucleic Acids Res,,,True
2d07e323c6ca944934316295569596dfe41367f4,PMC,Modulation of HIV-1 Gag/Gag-Pol frameshifting by tRNA abundance,http://dx.doi.org/10.1093/nar/gkz202,PMC6547452,30968122,CC BY-NC,"A hallmark of translation in human immunodeficiency virus type 1 (HIV-1) is a –1 programmed ribosome frameshifting event that produces the Gag-Pol fusion polyprotein. The constant Gag to Gag-Pol ratio is essential for the virion structure and infectivity. Here we show that the frameshifting efficiency is modulated by Leu-tRNA(Leu) that reads the UUA codon at the mRNA slippery site. This tRNA(Leu) isoacceptor is particularly rare in human cell lines derived from T-lymphocytes, the cells that are targeted by HIV-1. When UUA decoding is delayed, the frameshifting follows an alternative route, which maintains the Gag to Gag-Pol ratio constant. A second potential slippery site downstream of the first one is normally inefficient but can also support –1-frameshifting when altered by a compensatory resistance mutation in response to current antiviral drug therapy. Together these different regimes allow the virus to maintain a constant –1-frameshifting efficiency to ensure successful virus propagation.",2019 Jun 4,"['Korniy, Natalia', 'Goyal, Akanksha', 'Hoffmann, Markus', 'Samatova, Ekaterina', 'Peske, Frank', 'Pöhlmann, Stefan', 'Rodnina, Marina V']",Nucleic Acids Res,,,False
3061f05203159384dfbb2fd9b1d9a1ca7b98c8a6,PMC,Iranian Emergency Medical Service Response in Disaster; Report of three Earthquakes,http://dx.doi.org/10.22114/AJEM.v0i0.121,PMC6548112,31172124,CC BY-NC,"INTRODUCTION: The earthquake is one of the most natural catastrophic crises that can cause a lot of casualties. Considering an earthquake-prone country, Iran is ranked as one of the world's most dangerous countries OBJECTIVE: In this article, we describe the actions taken by emergency medical service (EMS) after the earthquake in Kermanshah, Varzaghan, and Bam and compared the strengths and weaknesses of the emergency response program and the limitations and challenges of this system in dealing with these major crises. METHOD: This study is a cross-sectional study that compares some of the information and findings related to three earthquakes that occurred in Iran, including Bam, Varzaghan and Sarpol-e-Zahab earthquakes. The data reported in the present article is descriptive and is based on various independent sources such as National Emergency Operation Center, Local Emergency Operations Center (EOC), the EMS of the country, the World Health Organization, the United Nations, the statistics website, the Forensic Data website, the International Institute of Seismology and Earthquake Engineering, conferences and personal interviews. To ensure the credibility of the information, the authors reported data that had been verified by two or more sources. RESULTS: The characteristics of the geographic area of the 3 earthquakes has been described. Post-earthquake response activities were described in details in subheadings including rapid warning and response, surge capacity plan, rapid response teams, emergency medical teams, increasing the capacity of health facilities, increasing transfer capacity, and handling, transportation and distribution of injuries. CONCLUSION: In the recent earthquake, had been occurred in Sarpol-e-Zahab, the health response of the country was largely satisfactory. The existence of structures such as EOC at various levels, the unified incident command system, emergency operations plan, and Medical Care Monitoring Center are among the most important reasons for satisfactory performance.",2019 Jan 14,"['Saberian, Peyman', 'Kolivand, Pir-Hossein', 'Hasani-Sharamin, Parisa', 'Dadashi, Fatemeh', 'Farhoud, Amir Reza']",Adv J Emerg Med,,,True
9660e4d54d854be62dc2e3ec086d1132a741efd9,PMC,Interleukin-35 as an Emerging Player in Tumor Microenvironment,http://dx.doi.org/10.7150/jca.29170,PMC6548173,31205568,CC BY-NC,"IL-35 is the newest member of IL-12 family. A dimeric protein consisting of two separate subunits has manifested suppressive actions on immune system, which is counterproductive in the context of cancers. Various reports have confirmed its inhibitory role on immune system which is carried out via formation of IL-35-producing regulatory T cells (iTr35), increased Treg development and suppressive Th17 cells growth. Although last decade has seen a great deal of scientific interest on this subject, the exact role, precise signal transduction and elaborative functions of IL-35 in tumor microenvironment (TME) remained elusive. Search for anti-IL-35 therapies have exhibited limited success in animal models. Contrarily, few studies have denied the idea that IL-35 plays a role in cancer. The purpose of this review is to analyze the reported scientific data on continuous symphony of IL-35 in cancers since the inception of former.",2019 May 12,"['Xue, Wenhua', 'Yan, Dan', 'Kan, Quancheng']",J Cancer,,,True
a72c48519bc3db9884b25a258aba41ccd333c162,PMC,A metaanalysis of bat phylogenetics and positive selection based on genomes and transcriptomes from 18 species,http://dx.doi.org/10.1073/pnas.1814995116,PMC6561249,31113885,CC BY-NC-ND,"Historically, the evolution of bats has been analyzed using a small number of genetic loci for many species or many genetic loci for a few species. Here we present a phylogeny of 18 bat species, each of which is represented in 1,107 orthologous gene alignments used to build the tree. We generated a transcriptome sequence of Hypsignathus monstrosus, the African hammer-headed bat, and additional transcriptome sequence for Rousettus aegyptiacus, the Egyptian fruit bat. We then combined these data with existing genomic and transcriptomic data from 16 other bat species. In the analysis of such datasets, there is no clear consensus on the most reliable computational methods for the curation of quality multiple sequence alignments since these public datasets represent multiple investigators and methods, including different source materials (chromosomal DNA or expressed RNA). Here we lay out a systematic analysis of parameters and produce an advanced pipeline for curating orthologous gene alignments from combined transcriptomic and genomic data, including a software package: the Mismatching Isoform eXon Remover (MIXR). Using this method, we created alignments of 11,677 bat genes, 1,107 of which contain orthologs from all 18 species. Using the orthologous gene alignments created, we assessed bat phylogeny and also performed a holistic analysis of positive selection acting in bat genomes. We found that 181 genes have been subject to positive natural selection. This list is dominated by genes involved in immune responses and genes involved in the production of collagens.",2019 Jun 4,"['Hawkins, John A.', 'Kaczmarek, Maria E.', 'Müller, Marcel A.', 'Drosten, Christian', 'Press, William H.', 'Sawyer, Sara L.']",Proc Natl Acad Sci U S A,,,False
5335dd626c2c607a3a6f7abefb0d341f0fd63164,PMC,A metaanalysis of bat phylogenetics and positive selection based on genomes and transcriptomes from 18 species,http://dx.doi.org/10.1073/pnas.1814995116,PMC6561249,31113885,CC BY-NC-ND,"Historically, the evolution of bats has been analyzed using a small number of genetic loci for many species or many genetic loci for a few species. Here we present a phylogeny of 18 bat species, each of which is represented in 1,107 orthologous gene alignments used to build the tree. We generated a transcriptome sequence of Hypsignathus monstrosus, the African hammer-headed bat, and additional transcriptome sequence for Rousettus aegyptiacus, the Egyptian fruit bat. We then combined these data with existing genomic and transcriptomic data from 16 other bat species. In the analysis of such datasets, there is no clear consensus on the most reliable computational methods for the curation of quality multiple sequence alignments since these public datasets represent multiple investigators and methods, including different source materials (chromosomal DNA or expressed RNA). Here we lay out a systematic analysis of parameters and produce an advanced pipeline for curating orthologous gene alignments from combined transcriptomic and genomic data, including a software package: the Mismatching Isoform eXon Remover (MIXR). Using this method, we created alignments of 11,677 bat genes, 1,107 of which contain orthologs from all 18 species. Using the orthologous gene alignments created, we assessed bat phylogeny and also performed a holistic analysis of positive selection acting in bat genomes. We found that 181 genes have been subject to positive natural selection. This list is dominated by genes involved in immune responses and genes involved in the production of collagens.",2019 Jun 4,"['Hawkins, John A.', 'Kaczmarek, Maria E.', 'Müller, Marcel A.', 'Drosten, Christian', 'Press, William H.', 'Sawyer, Sara L.']",Proc Natl Acad Sci U S A,,,True
bea239f61e1c445ba7d5b03c037709b856f18d30,PMC,Correction: Case characteristics among Middle East respiratory syndrome coronavirus outbreak and non-outbreak cases in Saudi Arabia from 2012 to 2015,http://dx.doi.org/10.1136/bmjopen-2016-011865corr1,PMC6561458,31175202,CC BY-NC,,2019 Jun 7,,BMJ Open,,,False
4b34166a75b4835a2743fabba60bf7ff23cf0087,PMC,Asthma associated with denatonium benzoate in a healthcare worker in Taiwan: A case report,http://dx.doi.org/10.1097/MD.0000000000015818,PMC6571374,31124982,CC BY-NC-ND,"RATIONALE: Denatonium benzoate is a useful indicator to ensure that the respirator being used by an individual forms a tight enough seal to adequately protect against unwanted airborne exposure. Although the relative risk for adverse effects of fit testing using denatonium benzoate is low, the absolute number of workers with adverse reactions may nevertheless be sizeable. PATIENT CONCERNS: A 34-year-old female nurse rapidly developed shortness of breath, cough, and agitation after denatonium benzoate fit testing. She had a history of allergy to shrimp, crab, mite, and disinfecting products (containing quaternary ammonium). DIAGNOSES: Due to typical symptoms of asthma after exposure to denatonium benzoate aerosol without any other apparent cause, serial pulmonary function tests indicating obstructive lung function and a higher concentration of immunoglobulin antibody E, she was diagnosed with allergic asthma. INTERVENTIONS: This patient was treated with omalizumab (Xolair), corticosteroid, β(2) agonist, montelukast, and Symbicort turbuhaler. OUTCOMES: The patient showed quick responses after treatment with diphenhydramine (intramuscularly), fenoterol HBr (inhalation), and prednisolone (oral). Approximately 2 weeks later, she suffered from difficulty breathing and asthmatic symptoms again when she was exposed to polished wax and disinfectant. She was treated with omalizumab (Xolair), corticosteroid, β(2) agonist, montelukast, and Symbicort turbuhaler. The patient was in stable condition with improvement in symptoms during follow-up. LESSONS: There may be potentially important health risks when healthcare workers are exposed to denatonium benzoate. Individuals who have a history of allergy to disinfecting products (containing quaternary ammonium) should avoid exposure of denatonium benzoate. More advanced research is needed in the future.",2019 May 24,"['Chen, Kou-Huang', 'Chung, Kuo-Mou', 'Chung, Ju-Hui', 'Chen, Kow-Tong']",Medicine (Baltimore),,,True
dee0aa9ba97f07a5635f79ce50cf17abaa2b699a,PMC,"Epidemiological characteristics of pulmonary tuberculosis in Shandong, China, 2005–2017: A retrospective study",http://dx.doi.org/10.1097/MD.0000000000015778,PMC6571395,31124969,CC BY-NC-ND,"This study aimed to analyze the epidemiology of pulmonary tuberculosis (PTB) and gained insight into the future TB control plan in China. We extracted epidemiological, clinical, and geographic data from TB prevention and control institutions in 6 cities of Shandong province, China, during 2005 to 2017. Among 224,480 diagnosed PTB, rural residents accounted for 93%, smear-positive PTB 52%, and new cases 92%. The incidence rate of overall PTB declined from 40.8 to 26.25 per 100,000 during 2005 to 2017. Except smear-negative PTB (7.57–19.87 per 100,000), the incidence of smear-positive PTB and all that stratified by age, sex, and treatment history decreased. With 80% reduction, the incidence of smear-positive PTB (6.38 per 100,000) and relapse cases (1.01 per 100,000) were already very low in 2017. With persistent efforts to combat TB, the disease burden had shifted from smear-positive PTB to smear-negative PTB. While new cases need continuous attention, further reducing the incidence of smear-negative PTB and elderly patients may have a greater impact on future TB control.",2019 May 24,"['Tao, Ning-Ning', 'Li, Yi-Fan', 'Wang, Shan-Shan', 'Liu, Yun-Xia', 'Liu, Jin-Yue', 'Song, Wan-Mei', 'Liu, Yao', 'Geng, Hong', 'Li, Huai-Chen']",Medicine (Baltimore),,,True
cfb3f090f09ba13429edc88b5f1d8a595df81fc1,PMC,Novel insights into endogenous RNA viral elements in Ixodes scapularis and other arbovirus vector genomes,http://dx.doi.org/10.1093/ve/vez010,PMC6580184,31249694,CC BY-NC,"Many emerging arboviruses are not transmitted by traditional mosquito vectors, but by lesser-studied arthropods such as ticks, midges, and sand flies. Small RNA (sRNA) silencing pathways are the main antiviral defence mechanism for arthropods, which lack adaptive immunity. Non-retroviral integrated RNA virus sequences (NIRVS) are one potential source of sRNAs which comprise these pathways. NIRVS are remnants of past germline RNA viral infections, where viral cDNA integrates into the host genome and is vertically transmitted. In Aedes mosquitoes, NIRVS are widespread and produce PIWI-interacting RNAs (piRNAs). These are hypothesised to target incoming viral transcripts to modulate viral titre, perhaps rendering the organism a more efficient arbovirus vector. To explore the NIRVS landscape in alternative arbovirus vectors, we validated the NIRVS landscape in Aedes spp. and then identified novel NIRVS in six medically relevant arthropods and also in Drosophila melanogaster. We identified novel NIRVS in Phlebotomus papatasi, Culicoides sonorensis, Rhipicephalus microplus, Anopheles gambiae, Culex quinquefasciatus, and Ixodes scapularis. Due to their unexpected abundance, we further characterised NIRVS in the blacklegged tick I. scapularis (n = 143). Interestingly, NIRVS are not enriched in R. microplus, another hard tick, suggesting this is an Ixodes-specific adaptation. I. scapularis NIRVS are enriched in bunya- and orthomyxo-like sequences, reflecting that ticks are a dominant host for these virus groups. Unlike in mosquitoes, I. scapularis NIRVS are more commonly derived from the non-structural region (replicase) of negative-sense viruses, as opposed to structural regions (e.g. glycoprotein). Like other arthropods, I. scapularis NIRVS preferentially integrate into genomic piRNA clusters, and serve as a template for primary piRNA production in the commonly used embryonic I. scapularis ISE6 cell line. Interestingly, we identified a two-fold enrichment of non-long terminal repeat (non-LTR) retrotransposons, in genomic proximity to NIRVS, contrasting with studeis in Ae. aegypti, where LTR retrotransposons are instead associated with NIRVS formation. We characterised NIRVS phylogeny and integration patterns in the important vector, I. scapularis, revealing they are distinct from those in Aedes spp. Future studies will explore the possible antiviral mechanism conferred by NIRVS to I. scapularis,which may help the transmission of pathogenic arboviruses. Finally, this study explored NIRVS as an untapped wealth of viral diversity in arthropods.",2019 Jun 18,"['Russo, Alice G', 'Kelly, Andrew G', 'Enosi Tuipulotu, Daniel', 'Tanaka, Mark M', 'White, Peter A']",Virus Evol,,,True
4cfc6c13359411fd900beeee260ce00a2e6c1b9d,PMC,Novel insights into endogenous RNA viral elements in Ixodes scapularis and other arbovirus vector genomes,http://dx.doi.org/10.1093/ve/vez010,PMC6580184,31249694,CC BY-NC,"Many emerging arboviruses are not transmitted by traditional mosquito vectors, but by lesser-studied arthropods such as ticks, midges, and sand flies. Small RNA (sRNA) silencing pathways are the main antiviral defence mechanism for arthropods, which lack adaptive immunity. Non-retroviral integrated RNA virus sequences (NIRVS) are one potential source of sRNAs which comprise these pathways. NIRVS are remnants of past germline RNA viral infections, where viral cDNA integrates into the host genome and is vertically transmitted. In Aedes mosquitoes, NIRVS are widespread and produce PIWI-interacting RNAs (piRNAs). These are hypothesised to target incoming viral transcripts to modulate viral titre, perhaps rendering the organism a more efficient arbovirus vector. To explore the NIRVS landscape in alternative arbovirus vectors, we validated the NIRVS landscape in Aedes spp. and then identified novel NIRVS in six medically relevant arthropods and also in Drosophila melanogaster. We identified novel NIRVS in Phlebotomus papatasi, Culicoides sonorensis, Rhipicephalus microplus, Anopheles gambiae, Culex quinquefasciatus, and Ixodes scapularis. Due to their unexpected abundance, we further characterised NIRVS in the blacklegged tick I. scapularis (n = 143). Interestingly, NIRVS are not enriched in R. microplus, another hard tick, suggesting this is an Ixodes-specific adaptation. I. scapularis NIRVS are enriched in bunya- and orthomyxo-like sequences, reflecting that ticks are a dominant host for these virus groups. Unlike in mosquitoes, I. scapularis NIRVS are more commonly derived from the non-structural region (replicase) of negative-sense viruses, as opposed to structural regions (e.g. glycoprotein). Like other arthropods, I. scapularis NIRVS preferentially integrate into genomic piRNA clusters, and serve as a template for primary piRNA production in the commonly used embryonic I. scapularis ISE6 cell line. Interestingly, we identified a two-fold enrichment of non-long terminal repeat (non-LTR) retrotransposons, in genomic proximity to NIRVS, contrasting with studeis in Ae. aegypti, where LTR retrotransposons are instead associated with NIRVS formation. We characterised NIRVS phylogeny and integration patterns in the important vector, I. scapularis, revealing they are distinct from those in Aedes spp. Future studies will explore the possible antiviral mechanism conferred by NIRVS to I. scapularis,which may help the transmission of pathogenic arboviruses. Finally, this study explored NIRVS as an untapped wealth of viral diversity in arthropods.",2019 Jun 18,"['Russo, Alice G', 'Kelly, Andrew G', 'Enosi Tuipulotu, Daniel', 'Tanaka, Mark M', 'White, Peter A']",Virus Evol,,,False
84d3fe51518523e73a65e73756e4496587e4f2f4,PMC,Ebola virus VP35 has novel NTPase and helicase-like activities,http://dx.doi.org/10.1093/nar/gkz340,PMC6582406,31066445,CC BY-NC,"Ebola virus (EBOV) is a non-segmented, negative-sense RNA virus (NNSV) in the family Filoviridae, and is recognized as one of the most lethal pathogens in the planet. For RNA viruses, cellular or virus-encoded RNA helicases play pivotal roles in viral life cycles by remodelling viral RNA structures and/or unwinding viral dsRNA produced during replication. However, no helicase or helicase-like activity has ever been found to associate with any NNSV-encoded proteins, and it is unknown whether the replication of NNSVs requires the participation of any viral or cellular helicase. Here, we show that despite of containing no conserved NTPase/helicase motifs, EBOV VP35 possesses the NTPase and helicase-like activities that can hydrolyse all types of NTPs and unwind RNA helices in an NTP-dependent manner, respectively. Moreover, guanidine hydrochloride, an FDA-approved compound and inhibitor of certain viral helicases, inhibited the NTPase and helicase-like activities of VP35 as well as the replication/transcription of an EBOV minigenome replicon in cells, highlighting the importance of VP35 helicase-like activity during EBOV life cycle. Together, our findings provide the first demonstration of the NTPase/helicase-like activity encoded by EBOV, and would foster our understanding of EBOV and NNSVs.",2019 Jun 20,"['Shu, Ting', 'Gan, Tianyu', 'Bai, Peng', 'Wang, Xiaotong', 'Qian, Qi', 'Zhou, Hui', 'Cheng, Qi', 'Qiu, Yang', 'Yin, Lei', 'Zhong, Jin', 'Zhou, Xi']",Nucleic Acids Res,,,True
ba4eedadb7aa198c1343816154d6b45a1e307da4,PMC,Ebola virus VP35 has novel NTPase and helicase-like activities,http://dx.doi.org/10.1093/nar/gkz340,PMC6582406,31066445,CC BY-NC,"Ebola virus (EBOV) is a non-segmented, negative-sense RNA virus (NNSV) in the family Filoviridae, and is recognized as one of the most lethal pathogens in the planet. For RNA viruses, cellular or virus-encoded RNA helicases play pivotal roles in viral life cycles by remodelling viral RNA structures and/or unwinding viral dsRNA produced during replication. However, no helicase or helicase-like activity has ever been found to associate with any NNSV-encoded proteins, and it is unknown whether the replication of NNSVs requires the participation of any viral or cellular helicase. Here, we show that despite of containing no conserved NTPase/helicase motifs, EBOV VP35 possesses the NTPase and helicase-like activities that can hydrolyse all types of NTPs and unwind RNA helices in an NTP-dependent manner, respectively. Moreover, guanidine hydrochloride, an FDA-approved compound and inhibitor of certain viral helicases, inhibited the NTPase and helicase-like activities of VP35 as well as the replication/transcription of an EBOV minigenome replicon in cells, highlighting the importance of VP35 helicase-like activity during EBOV life cycle. Together, our findings provide the first demonstration of the NTPase/helicase-like activity encoded by EBOV, and would foster our understanding of EBOV and NNSVs.",2019 Jun 20,"['Shu, Ting', 'Gan, Tianyu', 'Bai, Peng', 'Wang, Xiaotong', 'Qian, Qi', 'Zhou, Hui', 'Cheng, Qi', 'Qiu, Yang', 'Yin, Lei', 'Zhong, Jin', 'Zhou, Xi']",Nucleic Acids Res,,,False
bc47c74ccb7b9751aaa0fa71dd6b6a8265fdbc2c,PMC,Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments,http://dx.doi.org/10.1111/all.13624,PMC6587559,30276826,CC BY-NC,"Current data indicate that the “bronchiolitis” diagnosis comprises more than one condition. Clinically, pathophysiologically, and even genetically three main clusters of patients can be identified among children suffering from severe bronchiolitis (or first wheezing episode): (a) respiratory syncytial virus (RSV)‐induced bronchiolitis, characterized by young age of the patient, mechanical obstruction of the airways due to mucus and cell debris, and increased risk of recurrent wheezing. For this illness, an effective prophylactic RSV‐specific monoclonal antibody is available; (b) rhinovirus‐induced wheezing, associated with atopic predisposition of the patient and high risk of subsequent asthma development, which may, however, be reversed with systemic corticosteroids in those with severe illness; and (c) wheeze due to other viruses, characteristically likely to be less frequent and severe. Clinically, it is important to distinguish between these partially overlapping patient groups as they are likely to respond to different treatments. It appears that the first episode of severe bronchiolitis in under 2‐year‐old children is a critical event and an important opportunity for designing secondary prevention strategies for asthma. As data have shown bronchiolitis cannot simply be diagnosed using a certain cutoff age, but instead, as we suggest, using the viral etiology as the differentiating factor.",2019 Jan 25,"['Jartti, Tuomas', 'Smits, Hermelijn H.', 'Bønnelykke, Klaus', 'Bircan, Ozlem', 'Elenius, Varpu', 'Konradsen, Jon R.', 'Maggina, Paraskevi', 'Makrinioti, Heidi', 'Stokholm, Jakob', 'Hedlin, Gunilla', 'Papadopoulos, Nikolaos', 'Ruszczynski, Marek', 'Ryczaj, Klaudia', 'Schaub, Bianca', 'Schwarze, Jürgen', 'Skevaki, Chrysanthi', 'Stenberg‐Hammar, Katarina', 'Feleszko, Wojciech', None]",Allergy,,,True
f83b2d3bcbf4f5da7dbb22a53a5b2cb942d08a5e,PMC,"Protocol for a randomised, single-blind, two-arm, parallel-group controlled trial of the efficacy of rhinothermy delivered by nasal high flow therapy in the treatment of the common cold",http://dx.doi.org/10.1136/bmjopen-2018-028098,PMC6589000,31221888,CC BY-NC,"INTRODUCTION: The common cold is the most common infectious disease affecting humans. It is usually a self-limiting disease; however, the common cold can cause significant morbidity and has a substantial economic impact on society. Human rhinoviruses (HRVs), which cause up to two-thirds of colds, have temperature-dependent replication and most HRV strains replicate optimally at 33°C. Delivery of heated, humidified air to the upper airways has the potential to reduce viral replication, but evidence of the effectiveness of this treatment of the common cold is inconclusive. We plan to test the hypothesis that delivery of humidified air heated to 41°C at high flow, nasal high flow rhinothermy (rNHF), for 2 hours daily for five days is more effective in reducing common cold symptom severity and duration than five days of ‘sham’ rhinothermy. METHODS AND ANALYSIS: This is a randomised, single-blind, parallel-group trial comparing rNHF to ‘sham’ rhinothermy in the treatment of common cold. We plan to recruit 170 participants within 48 hours of the onset of symptoms of common cold and randomise them 1:1 to receive one of the two treatments for five days. The study duration is 14 days, which includes clinic visits on the first day of randomisation and four days post-randomisation, and a phone call on the 14th day. Participants will complete daily symptom diaries which include a symptom score, the Modified Jackson Score (MJS). The primary outcome is the MJS after four days. ETHICS AND DISSEMINATION: New Zealand Ethics Registration: 17/STH/174. Results will be published in a peer-reviewed medical journal, presented at academic meetings, and reported to participants. TRIAL REGISTRATION NUMBER: U1111-1194-4345 and ACTRN12617001340325; Pre-results.",2019 Jun 19,"['Bird, Grace', 'Braithwaite, Irene', 'Harper, James', 'McKinstry, Steven', 'Koorevaar, Iris', 'Fingleton, James', 'Semprini, Alex', 'Dilcher, Meik', 'Jennings, Lance', 'Weatherall, Mark', 'Beasley, Richard']",BMJ Open,,,True
1e05bf53ba39bc46ff6319529831aa0a06d610a6,PMC,"Protocol for a randomised, single-blind, two-arm, parallel-group controlled trial of the efficacy of rhinothermy delivered by nasal high flow therapy in the treatment of the common cold",http://dx.doi.org/10.1136/bmjopen-2018-028098,PMC6589000,31221888,CC BY-NC,"INTRODUCTION: The common cold is the most common infectious disease affecting humans. It is usually a self-limiting disease; however, the common cold can cause significant morbidity and has a substantial economic impact on society. Human rhinoviruses (HRVs), which cause up to two-thirds of colds, have temperature-dependent replication and most HRV strains replicate optimally at 33°C. Delivery of heated, humidified air to the upper airways has the potential to reduce viral replication, but evidence of the effectiveness of this treatment of the common cold is inconclusive. We plan to test the hypothesis that delivery of humidified air heated to 41°C at high flow, nasal high flow rhinothermy (rNHF), for 2 hours daily for five days is more effective in reducing common cold symptom severity and duration than five days of ‘sham’ rhinothermy. METHODS AND ANALYSIS: This is a randomised, single-blind, parallel-group trial comparing rNHF to ‘sham’ rhinothermy in the treatment of common cold. We plan to recruit 170 participants within 48 hours of the onset of symptoms of common cold and randomise them 1:1 to receive one of the two treatments for five days. The study duration is 14 days, which includes clinic visits on the first day of randomisation and four days post-randomisation, and a phone call on the 14th day. Participants will complete daily symptom diaries which include a symptom score, the Modified Jackson Score (MJS). The primary outcome is the MJS after four days. ETHICS AND DISSEMINATION: New Zealand Ethics Registration: 17/STH/174. Results will be published in a peer-reviewed medical journal, presented at academic meetings, and reported to participants. TRIAL REGISTRATION NUMBER: U1111-1194-4345 and ACTRN12617001340325; Pre-results.",2019 Jun 19,"['Bird, Grace', 'Braithwaite, Irene', 'Harper, James', 'McKinstry, Steven', 'Koorevaar, Iris', 'Fingleton, James', 'Semprini, Alex', 'Dilcher, Meik', 'Jennings, Lance', 'Weatherall, Mark', 'Beasley, Richard']",BMJ Open,,,True
3ced31e65e14cbd45628ea410b50d4e4841c9f50,PMC,"Protocol for a randomised, single-blind, two-arm, parallel-group controlled trial of the efficacy of rhinothermy delivered by nasal high flow therapy in the treatment of the common cold",http://dx.doi.org/10.1136/bmjopen-2018-028098,PMC6589000,31221888,CC BY-NC,"INTRODUCTION: The common cold is the most common infectious disease affecting humans. It is usually a self-limiting disease; however, the common cold can cause significant morbidity and has a substantial economic impact on society. Human rhinoviruses (HRVs), which cause up to two-thirds of colds, have temperature-dependent replication and most HRV strains replicate optimally at 33°C. Delivery of heated, humidified air to the upper airways has the potential to reduce viral replication, but evidence of the effectiveness of this treatment of the common cold is inconclusive. We plan to test the hypothesis that delivery of humidified air heated to 41°C at high flow, nasal high flow rhinothermy (rNHF), for 2 hours daily for five days is more effective in reducing common cold symptom severity and duration than five days of ‘sham’ rhinothermy. METHODS AND ANALYSIS: This is a randomised, single-blind, parallel-group trial comparing rNHF to ‘sham’ rhinothermy in the treatment of common cold. We plan to recruit 170 participants within 48 hours of the onset of symptoms of common cold and randomise them 1:1 to receive one of the two treatments for five days. The study duration is 14 days, which includes clinic visits on the first day of randomisation and four days post-randomisation, and a phone call on the 14th day. Participants will complete daily symptom diaries which include a symptom score, the Modified Jackson Score (MJS). The primary outcome is the MJS after four days. ETHICS AND DISSEMINATION: New Zealand Ethics Registration: 17/STH/174. Results will be published in a peer-reviewed medical journal, presented at academic meetings, and reported to participants. TRIAL REGISTRATION NUMBER: U1111-1194-4345 and ACTRN12617001340325; Pre-results.",2019 Jun 19,"['Bird, Grace', 'Braithwaite, Irene', 'Harper, James', 'McKinstry, Steven', 'Koorevaar, Iris', 'Fingleton, James', 'Semprini, Alex', 'Dilcher, Meik', 'Jennings, Lance', 'Weatherall, Mark', 'Beasley, Richard']",BMJ Open,,,True
f1ee53d1819104cd3f9629afb60c1e5c95f4e779,PMC,"Protocol for a randomised, single-blind, two-arm, parallel-group controlled trial of the efficacy of rhinothermy delivered by nasal high flow therapy in the treatment of the common cold",http://dx.doi.org/10.1136/bmjopen-2018-028098,PMC6589000,31221888,CC BY-NC,"INTRODUCTION: The common cold is the most common infectious disease affecting humans. It is usually a self-limiting disease; however, the common cold can cause significant morbidity and has a substantial economic impact on society. Human rhinoviruses (HRVs), which cause up to two-thirds of colds, have temperature-dependent replication and most HRV strains replicate optimally at 33°C. Delivery of heated, humidified air to the upper airways has the potential to reduce viral replication, but evidence of the effectiveness of this treatment of the common cold is inconclusive. We plan to test the hypothesis that delivery of humidified air heated to 41°C at high flow, nasal high flow rhinothermy (rNHF), for 2 hours daily for five days is more effective in reducing common cold symptom severity and duration than five days of ‘sham’ rhinothermy. METHODS AND ANALYSIS: This is a randomised, single-blind, parallel-group trial comparing rNHF to ‘sham’ rhinothermy in the treatment of common cold. We plan to recruit 170 participants within 48 hours of the onset of symptoms of common cold and randomise them 1:1 to receive one of the two treatments for five days. The study duration is 14 days, which includes clinic visits on the first day of randomisation and four days post-randomisation, and a phone call on the 14th day. Participants will complete daily symptom diaries which include a symptom score, the Modified Jackson Score (MJS). The primary outcome is the MJS after four days. ETHICS AND DISSEMINATION: New Zealand Ethics Registration: 17/STH/174. Results will be published in a peer-reviewed medical journal, presented at academic meetings, and reported to participants. TRIAL REGISTRATION NUMBER: U1111-1194-4345 and ACTRN12617001340325; Pre-results.",2019 Jun 19,"['Bird, Grace', 'Braithwaite, Irene', 'Harper, James', 'McKinstry, Steven', 'Koorevaar, Iris', 'Fingleton, James', 'Semprini, Alex', 'Dilcher, Meik', 'Jennings, Lance', 'Weatherall, Mark', 'Beasley, Richard']",BMJ Open,,,False
42832de41afe698335e24953f6d884ace6ec1b09,PMC,"Protocol for a randomised, single-blind, two-arm, parallel-group controlled trial of the efficacy of rhinothermy delivered by nasal high flow therapy in the treatment of the common cold",http://dx.doi.org/10.1136/bmjopen-2018-028098,PMC6589000,31221888,CC BY-NC,"INTRODUCTION: The common cold is the most common infectious disease affecting humans. It is usually a self-limiting disease; however, the common cold can cause significant morbidity and has a substantial economic impact on society. Human rhinoviruses (HRVs), which cause up to two-thirds of colds, have temperature-dependent replication and most HRV strains replicate optimally at 33°C. Delivery of heated, humidified air to the upper airways has the potential to reduce viral replication, but evidence of the effectiveness of this treatment of the common cold is inconclusive. We plan to test the hypothesis that delivery of humidified air heated to 41°C at high flow, nasal high flow rhinothermy (rNHF), for 2 hours daily for five days is more effective in reducing common cold symptom severity and duration than five days of ‘sham’ rhinothermy. METHODS AND ANALYSIS: This is a randomised, single-blind, parallel-group trial comparing rNHF to ‘sham’ rhinothermy in the treatment of common cold. We plan to recruit 170 participants within 48 hours of the onset of symptoms of common cold and randomise them 1:1 to receive one of the two treatments for five days. The study duration is 14 days, which includes clinic visits on the first day of randomisation and four days post-randomisation, and a phone call on the 14th day. Participants will complete daily symptom diaries which include a symptom score, the Modified Jackson Score (MJS). The primary outcome is the MJS after four days. ETHICS AND DISSEMINATION: New Zealand Ethics Registration: 17/STH/174. Results will be published in a peer-reviewed medical journal, presented at academic meetings, and reported to participants. TRIAL REGISTRATION NUMBER: U1111-1194-4345 and ACTRN12617001340325; Pre-results.",2019 Jun 19,"['Bird, Grace', 'Braithwaite, Irene', 'Harper, James', 'McKinstry, Steven', 'Koorevaar, Iris', 'Fingleton, James', 'Semprini, Alex', 'Dilcher, Meik', 'Jennings, Lance', 'Weatherall, Mark', 'Beasley, Richard']",BMJ Open,,,False
02450c2c82a1511cb5e1639d3b8438f69bbe11f0,PMC,GRASP depletion–mediated Golgi destruction decreases cell adhesion and migration via the reduction of α5β1 integrin,http://dx.doi.org/10.1091/mbc.E18-07-0462,PMC6589770,30649990,CC BY-NC-SA,"The Golgi apparatus is a membrane-bound organelle that serves as the center for trafficking and processing of proteins and lipids. To perform these functions, the Golgi forms a multilayer stacked structure held by GRASP55 and GRASP65 trans-oligomers and perhaps their binding partners. Depletion of GRASP proteins disrupts Golgi stack formation and impairs critical functions of the Golgi, such as accurate protein glycosylation and sorting. However, how Golgi destruction affects other cellular activities is so far unknown. Here, we report that depletion of GRASP proteins reduces cell attachment and migration. Interestingly, GRASP depletion reduces the protein level of α5β1 integrin, the major cell adhesion molecule at the surface of HeLa and MDA-MB-231 cells, due to decreased integrin protein synthesis. GRASP depletion also increases cell growth and total protein synthesis. These new findings enrich our understanding on the role of the Golgi in cell physiology and provide a potential target for treating protein-trafficking disorders.",2019 Mar 15,"['Ahat, Erpan', 'Xiang, Yi', 'Zhang, Xiaoyan', 'Bekier, Michael E.', 'Wang, Yanzhuang']",Mol Biol Cell,,,True
b4a9b6b4be03252d0b1e4c237603c3d2d13dc1f5,PMC,GRASP depletion–mediated Golgi destruction decreases cell adhesion and migration via the reduction of α5β1 integrin,http://dx.doi.org/10.1091/mbc.E18-07-0462,PMC6589770,30649990,CC BY-NC-SA,"The Golgi apparatus is a membrane-bound organelle that serves as the center for trafficking and processing of proteins and lipids. To perform these functions, the Golgi forms a multilayer stacked structure held by GRASP55 and GRASP65 trans-oligomers and perhaps their binding partners. Depletion of GRASP proteins disrupts Golgi stack formation and impairs critical functions of the Golgi, such as accurate protein glycosylation and sorting. However, how Golgi destruction affects other cellular activities is so far unknown. Here, we report that depletion of GRASP proteins reduces cell attachment and migration. Interestingly, GRASP depletion reduces the protein level of α5β1 integrin, the major cell adhesion molecule at the surface of HeLa and MDA-MB-231 cells, due to decreased integrin protein synthesis. GRASP depletion also increases cell growth and total protein synthesis. These new findings enrich our understanding on the role of the Golgi in cell physiology and provide a potential target for treating protein-trafficking disorders.",2019 Mar 15,"['Ahat, Erpan', 'Xiang, Yi', 'Zhang, Xiaoyan', 'Bekier, Michael E.', 'Wang, Yanzhuang']",Mol Biol Cell,,,False
51fff92f21f050e40ae7214b2b0b3a51e9079918,PMC,"Knowledge, Awareness, and Compliance of Disease Surveillance and Notification Among Jordanian Physicians in Residency Programs",http://dx.doi.org/10.1177/0046958019856508,PMC6589958,31220967,CC BY-NC,Health professionals’ knowledge and awareness of the disease surveillance is essential for reporting diseases to health departments. This study aimed to assess the knowledge and attitudes of Jordanian physicians toward public health surveillance of communicable disease. A cross-sectional study was conducted among resident doctors who were working in 4 main Ministry of Health hospitals and 2 teaching hospitals in Jordan in September 2017. A self-administered paper-based questionnaire was used to collect the data. The questionnaire collected information about sociodemographic and practice-related characteristics of physicians and included items to assess their knowledge of surveillance and reporting practices. This study included 223 physicians (152 males and 71 females). About 60.1% of the residents were graduates from medical schools in Jordan and the remaining (39.9%) were graduates from medical schools in other countries. Approximately two thirds of residents (62.3%) were doing their residency in Ministry of Health hospitals and the rest (37.7%) in 2 teaching hospitals. Only 44.8% of physicians had defined surveillance correctly. Only 27.4% of physicians had been educated or trained on surveillance. About 39.5% of physicians had filled at least one report form during their practice. The main reasons for not reporting mandatory diseases were high workload (49.8%) and being not trained on reporting diseases (46.6%). A relatively high percentage of physicians have insufficient knowledge of surveillance and reporting of notifiable communicable diseases. Training of physicians on surveillance and diseases notification is highly needed. The practice of disease notification should be enforced in Jordanian hospitals.,2019 Jun 21,"['Abdulrahim, Nansi', 'Alasasfeh, Ihab', 'Khader, Yousef S.', 'Iblan, Ibrahim']",Inquiry,,,True
9200568d5a5c88f0f1b203240e94e90f96546431,PMC,Development and evaluation of a new real‐time RT‐PCR assay for detecting the latest H9N2 influenza viruses capable of causing human infection,http://dx.doi.org/10.1111/1348-0421.12666,PMC6590187,30599081,CC BY-NC,"The H9N2 subtype of avian influenza A viruses (AIV) has spread among domestic poultry and wild birds worldwide. H9N2 AIV is sporadically transmitted to humans from avian species. A total of 42 laboratory‐confirmed cases of non‐fatal human infection with the Eurasian Y280 and G1 lineages have been reported in China, Hong Kong, Bangladesh and Egypt since 1997. H9N2 AIV infections in poultry have become endemic in Asia and the Middle East and are a major source of viral internal genes for other AIV subtypes, such that continuous monitoring of H9N2 AIV is recommended. In this study, a new, one‐step, real‐time RT‐PCR assay was developed to detect two major Eurasian H9 lineages of AIV capable of causing human infection. The sensitivity of this assay was determined using in vitro‐transcribed RNA, and the detection limit was approximately 3 copies/reaction. In this assay, no cross‐reactivity was observed against RNA from H1–15 subtypes of influenza A viruses, influenza B viruses and other viral respiratory pathogens. In addition, this assay could detect the H9 hemagglutinin (HA) gene from artificially reconstituted clinical samples spiked with H9N2 virus without any non‐specific reactions. Therefore, this assay is highly sensitive and specific for H9 HA detection. The assay is useful both for diagnostic purposes in cases of suspected human infection with influenza H9N2 viruses and for the surveillance of both avian and human influenza viruses.",2019 Jan 30,"['Saito, Shinji', 'Takayama, Ikuyo', 'Nakauchi, Mina', 'Nagata, Shiho', 'Oba, Kunihiro', 'Odagiri, Takato', 'Kageyama, Tsutomu']",Microbiol Immunol,,,True
eb7432cee2519eefd1a6672e1f0bc483c9527a8d,PMC,Analysis of Women’s Health Online News Articles Using Topic Modeling,http://dx.doi.org/10.24171/j.phrp.2019.10.3.07,PMC6590882,31263665,CC BY-NC-ND,"OBJECTIVES: This research aimed to understand the popularity of topics in the field of women’s health through analysis of online news articles which were chronologically classified and examined to determine how women’s health and diseases had changed over time. METHODS: Women’s health and disease news articles were collated from a popular news website between 1993 to 2015 and preprocessed using gynecological medical terminology, Korean words and nouns (excluding general nouns not related to women’s healthcare topics). The resultant articles (N = 7,710) were analyzed using the Latent Dirichlet Allocation algorithm and major topics were extracted. Topic trends were analyzed by year and period for women’s health. RESULTS: It was observed that most of the women’s health articles were focused on “Healthcare”, and 9 other topics were identified that represented a relatively small proportion in 1993–2000. In 2001–2005, most of the articles were focused on “Medical Services” and “Dietary Supplements” with some specific topics that peaked people’s interest, as compared to those focused on “Healthcare” in the 1990s. It was also observed that differences in the proportion of each topic was small after 2011. CONCLUSION: Changes in topics related to women’s disease were not clearly distinguished in the 1990s but this changed from 2001where articles related to “women disease” appeared as articles on the topics of various diseases.",2019 Jun,"['Cho, Kyoung Won', 'Kim, Shine Young', 'Woo, Young Woon']",Osong Public Health Res Perspect,,,True
e0981e6148fcddc3856151ebf5d7f99539c87bbf,PMC,"Stochastic and spatio-temporal analysis of the Middle East Respiratory Syndrome outbreak in South Korea, 2015",http://dx.doi.org/10.1016/j.idm.2019.06.002,PMC6595052,31297469,CC BY-NC-ND,"South Korea was free of the Middle East Respiratory Syndrome (MERS) until 2015. The MERS outbreak in South Korea during 2015 was the largest outbreak of the Coronavirus outside the Middle East. The major characteristic of this outbreak is inter- or intra-hospital transmission. This recent MERS outbreak in South Korea is examined and assessed in this paper. The main objectives of the study is to characterize the pattern of the MERS outbreak in South Korea based on a basic reproductive ratio, the probability of ultimate extinction of the disease, and the spatio-temporal proximity of occurrence between patients. The survival function method and stochastic branching process model are adapted to calculate the basic reproductive ratio and the probability of ultimate extinction of the disease. We further investigate the occurrence pattern of the outbreak using a spatio-temporal autocorrelation function.",2019 Jun 14,"Lee, Hyunsun",Infect Dis Model,,,False
f245596ffe228f1eb183e60f02428bf156bea645,PMC,Identification and Molecular Characterisation of Bovine Parainfluenza Virus-3 and Bovine Respiratory Syncytial Virus - First Report from Turkey,http://dx.doi.org/10.2478/jvetres-2019-0022,PMC6598183,31276055,CC BY-NC-ND,"INTRODUCTION: Bovine parainfluenza virus-3 (BPIV3) and bovine respiratory syncytial virus (BRSV) are the cause of respiratory disease in cattle worldwide. With other pathogens, they cause bovine respiratory disease complex (BRDC) in ruminants. The aim of the study was the detection and molecular characterisation of BPIV3 and BRSV from nasal swabs and lung samples of cows in and around the Erzurum region of eastern Turkey. MATERIAL AND METHODS: In total, 155 samples were collected. Of animals used in the study 92 were males and 63 females. The age of the animals was between 9 months and 5 years, mean 1.4 years. Most males were in the fattening period and being raised in open sheds; females were in the lactating period and kept in free stall barns. All samples were tested for the presence of viral genes using RT-PCR. Gene-specific primers in a molecular method (RT-PCR) identified BRSV (fusion gene) and BPIV3 (matrix gene) strains at the genus level. RESULTS: RNA from BRSV and BPIV3 was detected in two (1.29%) and three (1.93%) samples, respectively, one of each of which was sequenced and the sequences were aligned with reference virus strains. Phylogenetic analyses clustered the strains in genotype C/BPIV3 and subgroup III/BRSV. CONCLUSION: The results indicate that BRSV and BPIV3 contribute to bovine respiratory disease cases in Turkey. This is the first report on their detection and molecular characterisation in ruminants in Turkey.",2019 Jun 12,"['Timurkan, Mehmet Ozkan', 'Aydin, Hakan', 'Sait, Ahmet']",J Vet Res,,,True
b7aee99640edf75791f77fd9ab46534c27efdaae,PMC,"A Decade On: Systematic Review of ClinicalTrials.gov Infectious Disease Trials, 2007–2017",http://dx.doi.org/10.1093/ofid/ofz189,PMC6598302,31276007,CC BY-NC-ND,"BACKGROUND: Registration of interventional trials of Food and Drug Administration–regulated drug and biological products and devices became a legal requirement in 2007; the vast majority of these trials are registered in ClinicalTrials.gov. An analysis of ClinicalTrials.gov offers an opportunity to define the clinical research landscape; here we analyze 10 years of infectious disease (ID) clinical trial research. METHODS: Beginning with 166 415 interventional trials registered in ClinicalTrials.gov from 2007–2017, ID trials were selected by study conditions and interventions. Relevance to ID was confirmed through manual review, resulting in 13 707 ID trials and 152 708 non-ID trials. RESULTS: ID-related trials represented 6.9%–9.9% of all trials with no significant trend over time. ID trials tended to be more focused on treatment and prevention, with a focus on testing drugs, biologics, and vaccines. ID trials tended to be large, randomized, and nonblinded with a greater degree of international enrollment. Industry was the primary funding source for 45.2% of ID trials. Compared with the global burden of disease, human immunodeficiency virus/AIDS and hepatitis C trials were overrepresented, and lower respiratory tract infection trials were underrepresented. Hepatitis C trials fluctuated, keeping with a wave of new drug development. Influenza vaccine trials peaked during the 2009 H1N1 swine influenza outbreak. CONCLUSIONS: This study presents the most comprehensive characterization of ID clinical trials over the past decade. These results help define how clinical research aligns with clinical need. Temporal trends reflect changes in disease epidemiology and the impact of scientific discovery and market forces. Periodic review of ID clinical trials can help identify gaps and serve as a mechanism to realign resources.",2019 Apr 15,"['Jaffe, Ian S', 'Chiswell, Karen', 'Tsalik, Ephraim L']",Open Forum Infect Dis,,,True
bd9abaeae84a3ecea684e6bc7ddc64d4c6bb7cc0,PMC,What can we learn from China’s health system reform?,http://dx.doi.org/10.1136/bmj.l2349,PMC6598719,31217222,CC BY-NC,Qingyue Meng and colleagues assess what China’s health system reform has achieved and what needs to be done over the next decade,2019 Jun 20,"['Meng, Qingyue', 'Mills, Anne', 'Wang, Longde', 'Han, Qide']",BMJ,,,True
f794f4f008a3e169fc5c4f99c586355594caa296,PMC,Waterpipe smoking as a public health risk: Potential risk for transmission of MERS-CoV,http://dx.doi.org/10.1016/j.sjbs.2018.05.006,PMC6600605,31303822,CC BY-NC-ND,"The Middle East Respiratory Syndrome (MERS-CoV) emerged in the Kingdom of Saudi Arabia in 2012 causing a critical challenge to public health. The epidemiology of MERS-CoV remain enigmatic as human-to-human transmission is not fully understood. One possible scenario that might play a role in the virus transmission is the cultural waterpipe smoking. Cafés providing waterpipe smoking in cities within Saudi Arabia have been moved to areas outside city limits that frequently place them close to camels markets. We report results of a surveillance study wherein waterpipe hoses throughout several regions in Saudi Arabia were tested for the presence of MERS-CoV. A total of 2489 waterpipe samples were collected from cities where MERS-CoV cases were continuously recorded. MERS-CoV RNA wasn’t detected in collected samples. Irrespective of the negative results of our survey, the public health risk of waterpipe smoking should not be underestimated. To avoid a possible transmission within country where MERS-CoV is prevalent, we recommend the replacement of resusable hoses with “one-time-use” hoses in addition to a close inspection of waterpipe components to assure the appropriate cleaning and sanitization.",2019 Jul 3,"['Alagaili, Abdulaziz N.', 'Briese, Thomas', 'Amor, Nabil M.S.', 'Mohammed, Osama B.', 'Lipkin, W. Ian']",Saudi J Biol Sci,,,False
1f263aae1c1dcc053a85fc4444f0bc02a01e5b68,PMC,Respiratory syncytial virus in hematopoietic cell transplant recipients and patients with hematologic malignancies,http://dx.doi.org/10.3324/haematol.2018.215152,PMC6601091,31221784,CC BY-NC,"In the USA and other western nations, respiratory syncytial virus is one of the most commonly encountered respiratory viruses among patients who have been diagnosed with a hematologic malignancy or who have undergone a stem cell transplant. Multiple studies have been performed to evaluate the complications associated with respiratory syncytial virus infections. Other studies have evaluated therapeutic agents and strategies in which these agents can be used. There have also been numerous reports of outbreaks in bone marrow transplant units and oncology wards, where infection control measures have been invaluable in controlling the spread of disease. However, despite these novel approaches, respiratory syncytial virus continues to be potentially fatal in immunocompromised populations. In this review, we discuss the incidence of respiratory syncytial viral infections, risk factors associated with progression from upper respiratory tract infection to lower respiratory tract infection, other complications and outcomes (including mortality), management strategies, and prevention strategies in patients with a hematologic malignancy and in hematopoietic cell transplant recipients.",2019 Jul,"['Khawaja, Fareed', 'Chemaly, Roy F.']",Haematologica,,,True
72d70ffa18b4fd87526024500bf99d609b0e04cf,PMC,Respiratory syncytial virus in hematopoietic cell transplant recipients and patients with hematologic malignancies,http://dx.doi.org/10.3324/haematol.2018.215152,PMC6601091,31221784,CC BY-NC,"In the USA and other western nations, respiratory syncytial virus is one of the most commonly encountered respiratory viruses among patients who have been diagnosed with a hematologic malignancy or who have undergone a stem cell transplant. Multiple studies have been performed to evaluate the complications associated with respiratory syncytial virus infections. Other studies have evaluated therapeutic agents and strategies in which these agents can be used. There have also been numerous reports of outbreaks in bone marrow transplant units and oncology wards, where infection control measures have been invaluable in controlling the spread of disease. However, despite these novel approaches, respiratory syncytial virus continues to be potentially fatal in immunocompromised populations. In this review, we discuss the incidence of respiratory syncytial viral infections, risk factors associated with progression from upper respiratory tract infection to lower respiratory tract infection, other complications and outcomes (including mortality), management strategies, and prevention strategies in patients with a hematologic malignancy and in hematopoietic cell transplant recipients.",2019 Jul,"['Khawaja, Fareed', 'Chemaly, Roy F.']",Haematologica,,,False
eba708e6e1866e719f4b3671111e858f0062070d,PMC,Respiratory syncytial virus in hematopoietic cell transplant recipients and patients with hematologic malignancies,http://dx.doi.org/10.3324/haematol.2018.215152,PMC6601091,31221784,CC BY-NC,"In the USA and other western nations, respiratory syncytial virus is one of the most commonly encountered respiratory viruses among patients who have been diagnosed with a hematologic malignancy or who have undergone a stem cell transplant. Multiple studies have been performed to evaluate the complications associated with respiratory syncytial virus infections. Other studies have evaluated therapeutic agents and strategies in which these agents can be used. There have also been numerous reports of outbreaks in bone marrow transplant units and oncology wards, where infection control measures have been invaluable in controlling the spread of disease. However, despite these novel approaches, respiratory syncytial virus continues to be potentially fatal in immunocompromised populations. In this review, we discuss the incidence of respiratory syncytial viral infections, risk factors associated with progression from upper respiratory tract infection to lower respiratory tract infection, other complications and outcomes (including mortality), management strategies, and prevention strategies in patients with a hematologic malignancy and in hematopoietic cell transplant recipients.",2019 Jul,"['Khawaja, Fareed', 'Chemaly, Roy F.']",Haematologica,,,False
366057ee7dcf005190e239f45cdb054964e828db,PMC,"Assessing Zika Virus Transmission Within Households During an Outbreak in Martinique, 2015–2016",http://dx.doi.org/10.1093/aje/kwz091,PMC6601520,30995296,CC BY-NC,"Since 2015, Zika virus (ZIKV) has caused large epidemics in the Americas. Households are natural targets for control interventions, but quantification of the contribution of household transmission to overall spread is needed to guide policy. We developed a modeling framework to evaluate this contribution and key epidemic features of the ZIKV epidemic in Martinique in 2015–2016 from the joint analysis of a household transmission study (n = 68 households), a study among symptomatic pregnant women (n = 281), and seroprevalence surveys of blood donors (n = 457). We estimated that the probability of mosquito-mediated within-household transmission (from an infected member to a susceptible one) was 21% (95% credible interval (CrI): 5, 51), and the overall probability of infection from outside the household (i.e., in the community) was 39% (95% CrI: 27, 50). Overall, 50% (95% CrI: 43, 58) of the population was infected, with 22% (95% CrI: 5, 46) of infections acquired in households and 40% (95% CrI: 23, 56) being asymptomatic. The probability of presenting with Zika-like symptoms due to another cause was 16% (95% CrI: 10, 23). This study characterized the contribution of household transmission in ZIKV epidemics, demonstrating the benefits of integrating multiple data sets to gain more insight into epidemic dynamics.",2019 Jul 17,"['Cousien, Anthony', 'Abel, Sylvie', 'Monthieux, Alice', 'Andronico, Alessio', 'Calmont, Isabelle', 'Cervantes, Minerva', 'Césaire, Raymond', 'Gallian, Pierre', 'de Lamballerie, Xavier', 'Laouénan, Cédric', 'Najioullah, Fatiha', 'Pierre-François, Sandrine', 'Pircher, Mathilde', 'Salje, Henrik', 'ten Bosch, Quirine A', 'Cabié, André', 'Cauchemez, Simon']",Am J Epidemiol,,,True
b29af8a410b032d1159bf9cefe0654c43f3503d9,PMC,"Assessing Zika Virus Transmission Within Households During an Outbreak in Martinique, 2015–2016",http://dx.doi.org/10.1093/aje/kwz091,PMC6601520,30995296,CC BY-NC,"Since 2015, Zika virus (ZIKV) has caused large epidemics in the Americas. Households are natural targets for control interventions, but quantification of the contribution of household transmission to overall spread is needed to guide policy. We developed a modeling framework to evaluate this contribution and key epidemic features of the ZIKV epidemic in Martinique in 2015–2016 from the joint analysis of a household transmission study (n = 68 households), a study among symptomatic pregnant women (n = 281), and seroprevalence surveys of blood donors (n = 457). We estimated that the probability of mosquito-mediated within-household transmission (from an infected member to a susceptible one) was 21% (95% credible interval (CrI): 5, 51), and the overall probability of infection from outside the household (i.e., in the community) was 39% (95% CrI: 27, 50). Overall, 50% (95% CrI: 43, 58) of the population was infected, with 22% (95% CrI: 5, 46) of infections acquired in households and 40% (95% CrI: 23, 56) being asymptomatic. The probability of presenting with Zika-like symptoms due to another cause was 16% (95% CrI: 10, 23). This study characterized the contribution of household transmission in ZIKV epidemics, demonstrating the benefits of integrating multiple data sets to gain more insight into epidemic dynamics.",2019 Jul 17,"['Cousien, Anthony', 'Abel, Sylvie', 'Monthieux, Alice', 'Andronico, Alessio', 'Calmont, Isabelle', 'Cervantes, Minerva', 'Césaire, Raymond', 'Gallian, Pierre', 'de Lamballerie, Xavier', 'Laouénan, Cédric', 'Najioullah, Fatiha', 'Pierre-François, Sandrine', 'Pircher, Mathilde', 'Salje, Henrik', 'ten Bosch, Quirine A', 'Cabié, André', 'Cauchemez, Simon']",Am J Epidemiol,,,True
077a70059a89059bace1150d779cc911a2229c60,PMC,Generation and characterization of a monoclonal antibody against MERS-CoV targeting the spike protein using a synthetic peptide epitope-CpG-DNA-liposome complex,http://dx.doi.org/10.5483/BMBRep.2019.52.6.185,PMC6605520,30355437,CC BY-NC,"Middle East respiratory syndrome coronavirus (MERS-CoV) uses the spike (S) glycoprotein to recognize and enter target cells. In this study, we selected two epitope peptide sequences within the receptor binding domain (RBD) of the MERS-CoV S protein. We used a complex consisting of the epitope peptide of the MERS-CoV S protein and CpG-DNA encapsulated in liposome complex to immunize mice, and produced the monoclonal antibodies 506-2G10G5 and 492-1G10E4E2. The western blotting data showed that both monoclonal antibodies detected the S protein and immunoprecipitated the native form of the S protein. Indirect immunofluorescence and confocal analysis suggested strong reactivity of the antibodies towards the S protein of MERS-CoV virus infected Vero cells. Furthermore, the 506-2G10G5 monoclonal antibody significantly reduced plaque formation in MERS-CoV infected Vero cells compared to normal mouse IgG and 492-1G10E4E2. Thus, we successfully produced a monoclonal antibody directed against the RBD domain of the S protein which could be used in the development of diagnostics and therapeutic applications in the future.",2019 Jun 30,"['Park, Byoung Kwon', 'Maharjan, Sony', 'Lee, Su In', 'Kim, Jinsoo', 'Bae, Joon-Yong', 'Park, Man-Seong', 'Kwon, Hyung-Joo']",BMB Rep,,,True
13dfe6b793f6abab3135b4506eac31a0207b7552,PMC,Generation and characterization of a monoclonal antibody against MERS-CoV targeting the spike protein using a synthetic peptide epitope-CpG-DNA-liposome complex,http://dx.doi.org/10.5483/BMBRep.2019.52.6.185,PMC6605520,30355437,CC BY-NC,"Middle East respiratory syndrome coronavirus (MERS-CoV) uses the spike (S) glycoprotein to recognize and enter target cells. In this study, we selected two epitope peptide sequences within the receptor binding domain (RBD) of the MERS-CoV S protein. We used a complex consisting of the epitope peptide of the MERS-CoV S protein and CpG-DNA encapsulated in liposome complex to immunize mice, and produced the monoclonal antibodies 506-2G10G5 and 492-1G10E4E2. The western blotting data showed that both monoclonal antibodies detected the S protein and immunoprecipitated the native form of the S protein. Indirect immunofluorescence and confocal analysis suggested strong reactivity of the antibodies towards the S protein of MERS-CoV virus infected Vero cells. Furthermore, the 506-2G10G5 monoclonal antibody significantly reduced plaque formation in MERS-CoV infected Vero cells compared to normal mouse IgG and 492-1G10E4E2. Thus, we successfully produced a monoclonal antibody directed against the RBD domain of the S protein which could be used in the development of diagnostics and therapeutic applications in the future.",2019 Jun 30,"['Park, Byoung Kwon', 'Maharjan, Sony', 'Lee, Su In', 'Kim, Jinsoo', 'Bae, Joon-Yong', 'Park, Man-Seong', 'Kwon, Hyung-Joo']",BMB Rep,,,False
3a3cfdfd688cecf04f3d9beb9b98e61d77159497,PMC,Sources and symptoms of stress among nurses in the first Chinese anti-Ebola medical team during the Sierra Leone aid mission: A qualitative study,http://dx.doi.org/10.1016/j.ijnss.2019.03.007,PMC6608674,31406890,CC BY-NC-ND,"OBJECTIVE: This study investigated the sources of stress, corresponding symptoms, and stress relief among nurses of the first Chinese anti-Ebola medical team during the Sierra Leone aid mission. METHOD: A purposive sampling method was used and 10 nurses were selected from the first Chinese anti-Ebola medical team that was dispatched to Sierra Leone. Data were collected via phone and semi-structured interviews, then analyzed using Colaizzi's seven-step method. RESULTS: The data showed three major themes: (1) The causes of stress during the Sierra Leone aid mission mainly related to unsafety, responsibility, and unfamiliarity; (2) Physical, cognitive, emotional, and behavioral symptoms were documented; (3) Nurses experienced relief from stress after the mission. CONCLUSION: Targeted measures, proper responses and good community support can effectively lower stress among nurses on anti-Ebola missions.",2019 Mar 8,"['Liu, Chunzi', 'Wang, Huaming', 'Zhou, Lin', 'Xie, Hui', 'Yang, Huiyin', 'Yu, Yanbo', 'Sha, Huayan', 'Yang, Ying', 'Zhang, Xin']",Int J Nurs Sci,,,False
c6aea56ae2d57157e5a84857bc2c166d6a9a0105,PMC,Epidemiological Investigation of the Outbreak of Acute Respiratory Infection caused by Adenovirus Type B55 in a Physical Education School in 2017,http://dx.doi.org/10.3947/ic.2019.51.2.119,PMC6609751,31270991,CC BY-NC,"BACKGROUND: On May 19, 2017, the cluster of 6 acute respiratory infections due to adenovirus in the swimming department of a physical education school (School J) was reported to Korea Centers for Disease Control and Prevention. An epidemiological investigation was conducted to identify the transmission route of the infection and to control the outbreak. MATERIALS AND METHODS: A retrospective cohort study (Study 1) was conducted on students and teachers of the athletic departments using the swimming pool, and a prospective surveillance (Study 2) was conducted on all students and teachers of the School J. A case was defined as any student and school personnel who developed more than two of the following symptoms from April 10 to July 2, 2017: fever, sore throat, cough, rhinorrhea, or headache. Relative risks (RRs) were calculated to compare the attack rates according to potential risk factors. Multivariable logistic regression was performed to identify the risk factors for infection in the outbreak. RESULTS: 47 cases were identified: 33 (55.9%) cases occurred among 59 students and teachers in Study 1 and 14 (3.9%) among 362 students and school personnel in Study 2. There were 18 laboratory confirmed adenovirus infection cases. The common symptoms were headache (71.7%), fever (69.6%), rhinorrhea (63.0%), sputum (56.5%), and sore throat (54.3%). 23.9% of the cases were accompanied with diarrhea and 19.6% with eye congestion. None of the cases developed pneumonia. 32.6% of the cases were hospitalized. In Study 1, attack rate in the swimming department was higher than that in others (RR: 1.90; 95% confidence interval [CI]: 1.01-3.60). In Study 2, being a member of the shooting department (RR: 20.70; 95% CI: 4.90-87.47) and being a first year high school student (RR: 10.95; 95% CI: 2.90-41.33) were identified as risk factors for the infections. Genetic analyses of the adenoviruses showed 100% identical sequence in homology and confirmed the human adenovirus B55 (HAdV-B55). No adenovirus was detected at examining the water and environment of the swimming pool and dormitory. CONCLUSION: The outbreak is inferred to be occurred via propagated transmission among the students in the same athletic department, while the students with symptoms of respiratory infection continued performing school activities without any restrictions. Infection control measures such as early detection of symptoms of respiratory infection and restriction of group activity are necessary to prevent respiratory infection outbreak in the communal living setting.",2019 Jun 28,"['Song, Jeongsuk', 'Lee, Hyerim', 'Cho, Enhi']",Infect Chemother,,,True
79f2edaa6e757d6032bd265f4735512738f51797,PMC,Pathogenesis of oral type I feline infectious peritonitis virus (FIPV) infection: Antibody-dependent enhancement infection of cats with type I FIPV via the oral route,http://dx.doi.org/10.1292/jvms.18-0702,PMC6612493,31019150,CC BY-NC-ND,"Feline infectious peritonitis virus (FIPV) causes a severe, immune-mediated disease called FIP in domestic and wild cats. It is unclear whether FIP transmits from cat to cat through the oral route of FIPV infection, and the reason for this includes that FIP is caused by oral inoculation with some FIPV strains (e.g., type II FIPV WSU 79-1146), but is not caused by other FIPV (e.g., type I FIPV KU-2 strain: FIPV-I KU-2). In this study, when cats passively immunized with anti-FIPV-I KU-2 antibodies were orally inoculated with FIPV-I KU-2, FIP was caused at a 50% probability, i.e., FIPV not causing FIP through oral infection caused FIP by inducing antibody-dependent enhancement. Many strains of type I FIPV do not cause FIP by inoculation through the oral route in cats. Based on the findings of this study, type I FIPV which orally infected cats may cause FIP depending on the condition.",2019 Jun 23,"['TAKANO, Tomomi', 'YAMADA, Shinji', 'DOKI, Tomoyoshi', 'HOHDATSU, Tsutomu']",J Vet Med Sci,,,True
7ab7699be02b690053288d296a55d2cead606c40,PMC,Delicate structural coordination of the Severe Acute Respiratory Syndrome coronavirus Nsp13 upon ATP hydrolysis,http://dx.doi.org/10.1093/nar/gkz409,PMC6614802,31131400,CC BY-NC,"To date, an effective therapeutic treatment that confers strong attenuation toward coronaviruses (CoVs) remains elusive. Of all the potential drug targets, the helicase of CoVs is considered to be one of the most important. Here, we first present the structure of the full-length Nsp13 helicase of SARS-CoV (SARS-Nsp13) and investigate the structural coordination of its five domains and how these contribute to its translocation and unwinding activity. A translocation model is proposed for the Upf1-like helicase members according to three different structural conditions in solution characterized through H/D exchange assay, including substrate state (SARS-Nsp13-dsDNA bound with AMPPNP), transition state (bound with ADP-AlF(4)(−)) and product state (bound with ADP). We observed that the β19–β20 loop on the 1A domain is involved in unwinding process directly. Furthermore, we have shown that the RNA dependent RNA polymerase (RdRp), SARS-Nsp12, can enhance the helicase activity of SARS-Nsp13 through interacting with it directly. The interacting regions were identified and can be considered common across CoVs, which provides new insights into the Replication and Transcription Complex (RTC) of CoVs.",2019 Jul 9,"['Jia, Zhihui', 'Yan, Liming', 'Ren, Zhilin', 'Wu, Lijie', 'Wang, Jin', 'Guo, Jing', 'Zheng, Litao', 'Ming, Zhenhua', 'Zhang, Lianqi', 'Lou, Zhiyong', 'Rao, Zihe']",Nucleic Acids Res,,,True
416f793bce2245b6bcaca43307e6a0ac09111896,PMC,Delicate structural coordination of the Severe Acute Respiratory Syndrome coronavirus Nsp13 upon ATP hydrolysis,http://dx.doi.org/10.1093/nar/gkz409,PMC6614802,31131400,CC BY-NC,"To date, an effective therapeutic treatment that confers strong attenuation toward coronaviruses (CoVs) remains elusive. Of all the potential drug targets, the helicase of CoVs is considered to be one of the most important. Here, we first present the structure of the full-length Nsp13 helicase of SARS-CoV (SARS-Nsp13) and investigate the structural coordination of its five domains and how these contribute to its translocation and unwinding activity. A translocation model is proposed for the Upf1-like helicase members according to three different structural conditions in solution characterized through H/D exchange assay, including substrate state (SARS-Nsp13-dsDNA bound with AMPPNP), transition state (bound with ADP-AlF(4)(−)) and product state (bound with ADP). We observed that the β19–β20 loop on the 1A domain is involved in unwinding process directly. Furthermore, we have shown that the RNA dependent RNA polymerase (RdRp), SARS-Nsp12, can enhance the helicase activity of SARS-Nsp13 through interacting with it directly. The interacting regions were identified and can be considered common across CoVs, which provides new insights into the Replication and Transcription Complex (RTC) of CoVs.",2019 Jul 9,"['Jia, Zhihui', 'Yan, Liming', 'Ren, Zhilin', 'Wu, Lijie', 'Wang, Jin', 'Guo, Jing', 'Zheng, Litao', 'Ming, Zhenhua', 'Zhang, Lianqi', 'Lou, Zhiyong', 'Rao, Zihe']",Nucleic Acids Res,,,False
6c51eafc88ddf46d27452c1a1b7a009c5341e848,PMC,Transcription attenuation-derived small RNA rnTrpL regulates tryptophan biosynthesis gene expression in trans,http://dx.doi.org/10.1093/nar/gkz274,PMC6614838,30993322,CC BY-NC,"Ribosome-mediated transcription attenuation is a basic posttranscriptional regulation mechanism in bacteria. Liberated attenuator RNAs arising in this process are generally considered nonfunctional. In Sinorhizobium meliloti, the tryptophan (Trp) biosynthesis genes are organized into three operons, trpE(G), ppiD-trpDC-moaC-moeA, and trpFBA-accD-folC, of which only the first one, trpE(G), contains a short ORF (trpL) in the 5′-UTR and is regulated by transcription attenuation. Under conditions of Trp sufficiency, transcription is terminated between trpL and trpE(G), and a small attenuator RNA, rnTrpL, is produced. Here, we show that rnTrpL base-pairs with trpD and destabilizes the polycistronic trpDC mRNA, indicating rnTrpL-mediated downregulation of the trpDC operon in trans. Although all three trp operons are regulated in response to Trp availability, only in the two operons trpE(G) and trpDC the Trp-mediated regulation is controlled by rnTrpL. Together, our data show that the trp attenuator coordinates trpE(G) and trpDC expression posttranscriptionally by two fundamentally different mechanisms: ribosome-mediated transcription attenuation in cis and base-pairing in trans. Also, we present evidence that rnTrpL-mediated regulation of trpDC genes expression in trans is conserved in Agrobacterium and Bradyrhizobium, suggesting that the small attenuator RNAs may have additional conserved functions in the control of bacterial gene expression.",2019 Jul 9,"['Melior, Hendrik', 'Li, Siqi', 'Madhugiri, Ramakanth', 'Stötzel, Maximilian', 'Azarderakhsh, Saina', 'Barth-Weber, Susanne', 'Baumgardt, Kathrin', 'Ziebuhr, John', 'Evguenieva-Hackenberg, Elena']",Nucleic Acids Res,,,True
1b44eb4e309e0a843a7c308eeddab0e852704a19,PMC,Prevalence and related factors of post-traumatic stress disorder among medical staff members exposed to H7N9 patients,http://dx.doi.org/10.1016/j.ijnss.2016.12.002,PMC6626070,31406720,CC BY-NC-ND,"OBJECTIVE: This study aimed to evaluate the prevalence and related factors of post-traumatic stress disorder (PTSD) symptoms among doctors and nurses who were exposed to H7N9 patients during the H7N9 influenza epidemic. To provide scientific basis for promoting the physical and psychological health of these staff members. METHOD: The 102 medical staff workers who were exposed to H7N9 patients were recruited through convenient sampling between January 2015 and May 2016. We used a self-reported questionnaire, the PTSD Checklist-Civilian Version (PCL-C), to evaluate the PTSD symptoms among doctors and nurses from an intensive care unit (n = 61), a respiratory department (n = 20), and an emergency department (n = 21). We then analyzed the related factors. RESULTS: Around 20.59% of the tested doctors and nurses showed PTSD symptoms. The sample had a mean PCL-C score of 30.00 ± 9.95. The differences in the scores of doctors and nurses with different genders, ages, professional titles, contact frequencies, trainings, and experiences were statistically significant (P < 0.05, P < 0.01). Moreover, t-tests and one-way analysis of variance showed that nurses received higher scores than doctors, female participants received higher scores than male participants, and the participants with low professional title and high contact frequency, aged between 20 years and 30 years, with less than five years of work experience, having not received related training and with no related experience obtained higher PCL-C scores than the others (P < 0.05, P < 0.01). CONCLUSION: The PTSD level of doctors and nurses after their exposure to H7N9 patients was high, which warrant further research. Health and medical institutions should pay attention to the physical and psychological health of these staff members.",2016 Dec 11,"['Tang, Liling', 'Pan, Lingling', 'Yuan, Liping', 'Zha, Lei']",Int J Nurs Sci,,,False
52d9b4cc7d694101b07e611e194f0115f359249a,PMC,Parasites and wildlife in a changing world: The vector-host- pathogen interaction as a learning case,http://dx.doi.org/10.1016/j.ijppaw.2019.05.011,PMC6630057,31341772,CC BY-NC-ND,"In the Anthropocene context, changes in climate, land use and biodiversity are considered among the most important anthropogenic factors affecting parasites-host interaction and wildlife zoonotic diseases emergence. Transmission of vector borne pathogens are particularly sensitive to these changes due to the complexity of their cycle, where the transmission of a microparasite depends on the interaction between its vector, usually a macroparasite, and its reservoir host, in many cases represented by a wildlife vertebrate. The scope of this paper focuses on the effect of some major, fast-occurring anthropogenic changes on the vectorial capacity for tick and mosquito borne pathogens. Specifically, we review and present the latest advances regarding two emerging vector-borne viruses in Europe: Tick-borne encephalitis virus (TBEV) and West Nile virus (WNV). In both cases, variation in vector to host ratio is critical in determining the intensity of pathogen transmission and consequently infection hazard for humans. Forecasting vector-borne disease hazard under the global change scenarios is particularly challenging, requiring long term studies based on a multidisciplinary approach in a One-Health framework.",2019 Jun 12,"['Rizzoli, Annapaola', 'Tagliapietra, Valentina', 'Cagnacci, Francesca', 'Marini, Giovanni', 'Arnoldi, Daniele', 'Rosso, Fausta', 'Rosà, Roberto']",Int J Parasitol Parasites Wildl,,,False
fad2e25d3eb22c2837bc1dc311d83a79d65b2889,PMC,Refractory ventricular tachycardia storm associated with severe hypokalemia in Fanconi syndrome,http://dx.doi.org/10.1016/j.hrcr.2019.04.003,PMC6630180,31341780,CC BY-NC-ND,,2019 Apr 24,"['Rodriguez, Alex P.', 'Badiye, Amit', 'Lambrakos, Litsa K.', 'Ghodsizad, Ali', 'Myerburg, Robert J.', 'Goldberger, Jeffrey J.']",HeartRhythm Case Rep,,,False
5ca05808cfc6d2139bc1ab6112d67dff9411f9ce,PMC,Social Media and the Dissemination of Prepublication Data in Surgical Fields,http://dx.doi.org/10.1097/GOX.0000000000002303,PMC6635179,31624692,CC BY-NC-ND,"BACKGROUND: This review investigates the use of social media at surgical conferences and possible effects of prepublication data release in surgical fields. Potential risks include patient harm by the preliminary application of research that lacks sufficient peer review, infringements on intellectual property, and loss of “research novelty.” METHODS: A literature review of the current use of social media in dispersion of prepublication data was performed. Current submission guidelines for surgical conferences and journals were analyzed for data release embargos and social media use policies. RESULTS: Conference abstract guidelines mentioned data embargos half of the time and the use of social media less than one third of the time. Eighty percentage of journal instructions to authors contained guidelines on both. CONCLUSIONS: In nonsurgical fields, the appropriateness of the use of social media to release prepublication data is increasingly being discussed. Little guidance exists on how surgical conference attendees should use social media while at conferences. Given the potential for patient harm and negative impact on intellectual property and attribution, further discussion is warranted. INTRODUCCIÓN: Esta crítica investiga el uso de las redes sociales en las conferencias quirúrgicas y los efectos posibles de los datos pre-publicados en cirugía. Los riesgos probables incluyen: daño al paciente causado por la aplicación prematura de las investigaciones sin bastante análisis, violación de la propiedad intelectual, y perdido de “novedad de investigación.” METODOLOGÍA: Un repaso fue hecho sobre el rol de las redes sociales en la propagación de los datos pre-publicados. Las normas actuales para la entrega de las conferencias y los periódicos quirúrgicos claves fueron analizadas por las reglas gobernando el uso de las redes sociales y los embargos del lanzamiento de datos. RESULTADOS: Las reglas generales sobre la entrega de abstractos para las conferencias mencionaron los embargos de datos la mitad del tiempo mientras que estas mismas reglas mencionaron el uso de las redes sociales menos que un tercio el tiempo. 80% de las instrucciones de los periódicos dirigidas a los autores tuvieron las reglas generales sobre los dos: los embargos de datas y las redes sociales. CONCLUSIONES: En las especialidades non-quirúrgicas, la pertinencia del uso de las redes sociales para lanzar el dato pre-publicado es discutida con más frecuencia. No existen normas sobre cómo se usan las redes sociales durante las conferencias. Dado el daño potencial al paciente y el impacto negativo en la propiedad y la atribución intelectuales, más discusión está obligatoria.",2019 Jun 19,"['Akhavan, Arya A.', 'Ndem, Idorenyin E.', 'Kalliainen, Loree K.']",Plast Reconstr Surg Glob Open,,,True
fbf3cc84b1d412693330fffee86bef8fbdda3b07,PMC,Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders,http://dx.doi.org/10.1002/glia.23529,PMC6635749,30378163,CC BY-NC,"Microglia are prominent immune cells in the central nervous system (CNS) and are critical players in both neurological development and homeostasis, and in neurological diseases when dysfunctional. Our previous understanding of the phenotypes and functions of microglia has been greatly extended by a dearth of recent investigations. Distinct genetically defined subsets of microglia are now recognized to perform their own independent functions in specific conditions. The molecular profiling of single microglial cells indicates extensively heterogeneous reactions in different neurological disorders, resulting in multiple potentials for crosstalk with other kinds of CNS cells such as astrocytes and neurons. In settings of neurological diseases it could thus be prudent to establish effective cell‐based therapies by targeting entire microglial networks. Notably, activated microglial depletion through genetic targeting or pharmacological therapies within a suitable time window can stimulate replenishment of the CNS niche with new microglia. Additionally, enforced repopulation through provision of replacement cells also represents a potential means of exchanging dysfunctional with functional microglia. In each setting the newly repopulated microglia might have the potential to resolve ongoing neuroinflammation. In this review, we aim to summarize the most recent knowledge of microglia and to highlight microglial depletion and subsequent repopulation as a promising cell replacement therapy. Although glial cell replacement therapy is still in its infancy and future translational studies are still required, the approach is scientifically sound and provides new optimism for managing the neurotoxicity and neuroinflammation induced by activated microglia.",2019 Feb 30,"['Han, Jinming', 'Zhu, Keying', 'Zhang, Xing‐Mei', 'Harris, Robert A.']",Glia,,,True
eaeab732c9c3e204526d8e1ea34cf40e7f37731f,PMC,Plasma and tissue angiotensin‐converting enzyme 2 activity and plasma equilibrium concentrations of angiotensin peptides in dogs with heart disease,http://dx.doi.org/10.1111/jvim.15548,PMC6639469,31254308,CC BY-NC,"BACKGROUND: Angiotensin‐converting enzyme 2 (ACE2) is a homologue of angiotensin‐converting enzyme (ACE) and produces angiotensin peptides (APs), such as angiotensin 1‐9 and 1‐7 that are vasodilatory and natriuretic, and act to counterbalance angiotensin II. HYPOTHESIS: Evidence of ACE2 can be found in tissues and plasma of dogs. Equilibrium concentrations of renin angiotensin aldosterone system (RAAS) APs differ in dogs with heart disease compared to healthy dogs and recombinant human ACE2 (rhACE2) alters relative concentrations of APs. ANIMALS: Forty‐nine dogs with and 34 dogs without heart disease. METHODS: Immunohistochemistry and assays for tissue and plasma ACE2 activity and equilibrium concentrations of plasma RAAS APs were performed. RESULTS: Immunolabeling for ACE2 was present in kidney and myocardial tissue. Median plasma ACE2 activity was significantly increased in dogs with congestive heart failure (CHF; 6.9 mU/mg; interquartile range [IQR], 5.1‐12.1) as compared to control (2.2 mU/mg; IQR, 1.8‐3.0; P = .0003). Plasma equilibrium analysis of RAAS APs identified significant increases in the median concentrations of beneficial APs, such as angiotensin 1‐7, in dogs with CHF (486.7 pg/mL; IQR, 214.2‐1168) as compared to those with preclinical disease (41.0 pg/mL; IQR, 27.4‐45.1; P < .0001) or control (11.4 pg/mL; IQR, 7.1‐25.3; P = .01). Incubation of plasma samples from dogs with CHF with rhACE2 increased beneficial APs, such as angiotensin 1‐9 (preincubation, 10.3 pg/mL; IQR, 4.4‐37.2; postincubation, 2431 pg/mL; IQR, 1355‐3037; P = .02), while simultaneously decreasing maladaptive APs, such as angiotensin II (preincubation, 53.4 pg/mL; IQR, 28.6‐226.4; postincubation, 2.4 pg/mL; IQR, 0.50‐5.8; P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Recognition of the ACE2 system expands the conventional view of the RAAS in the dog and represents an important potential therapeutic target.",2019 Jun 28 Jul-Aug,"['Larouche‐Lebel, Éva', 'Loughran, Kerry A.', 'Oyama, Mark A.', 'Solter, Phil F.', 'Laughlin, Danielle S.', 'Sánchez, Melissa D.', 'Assenmacher, Charles‐Antoine', 'Fox, Philip R.', 'Fries, Ryan C.']",J Vet Intern Med,,,True
0548badb833de84544d36d72f00b8706b97e19b1,PMC,Plasma and tissue angiotensin‐converting enzyme 2 activity and plasma equilibrium concentrations of angiotensin peptides in dogs with heart disease,http://dx.doi.org/10.1111/jvim.15548,PMC6639469,31254308,CC BY-NC,"BACKGROUND: Angiotensin‐converting enzyme 2 (ACE2) is a homologue of angiotensin‐converting enzyme (ACE) and produces angiotensin peptides (APs), such as angiotensin 1‐9 and 1‐7 that are vasodilatory and natriuretic, and act to counterbalance angiotensin II. HYPOTHESIS: Evidence of ACE2 can be found in tissues and plasma of dogs. Equilibrium concentrations of renin angiotensin aldosterone system (RAAS) APs differ in dogs with heart disease compared to healthy dogs and recombinant human ACE2 (rhACE2) alters relative concentrations of APs. ANIMALS: Forty‐nine dogs with and 34 dogs without heart disease. METHODS: Immunohistochemistry and assays for tissue and plasma ACE2 activity and equilibrium concentrations of plasma RAAS APs were performed. RESULTS: Immunolabeling for ACE2 was present in kidney and myocardial tissue. Median plasma ACE2 activity was significantly increased in dogs with congestive heart failure (CHF; 6.9 mU/mg; interquartile range [IQR], 5.1‐12.1) as compared to control (2.2 mU/mg; IQR, 1.8‐3.0; P = .0003). Plasma equilibrium analysis of RAAS APs identified significant increases in the median concentrations of beneficial APs, such as angiotensin 1‐7, in dogs with CHF (486.7 pg/mL; IQR, 214.2‐1168) as compared to those with preclinical disease (41.0 pg/mL; IQR, 27.4‐45.1; P < .0001) or control (11.4 pg/mL; IQR, 7.1‐25.3; P = .01). Incubation of plasma samples from dogs with CHF with rhACE2 increased beneficial APs, such as angiotensin 1‐9 (preincubation, 10.3 pg/mL; IQR, 4.4‐37.2; postincubation, 2431 pg/mL; IQR, 1355‐3037; P = .02), while simultaneously decreasing maladaptive APs, such as angiotensin II (preincubation, 53.4 pg/mL; IQR, 28.6‐226.4; postincubation, 2.4 pg/mL; IQR, 0.50‐5.8; P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Recognition of the ACE2 system expands the conventional view of the RAAS in the dog and represents an important potential therapeutic target.",2019 Jun 28 Jul-Aug,"['Larouche‐Lebel, Éva', 'Loughran, Kerry A.', 'Oyama, Mark A.', 'Solter, Phil F.', 'Laughlin, Danielle S.', 'Sánchez, Melissa D.', 'Assenmacher, Charles‐Antoine', 'Fox, Philip R.', 'Fries, Ryan C.']",J Vet Intern Med,,,False
304397b339265e6096999d27e83cefb84842e8f2,PMC,Plasma and tissue angiotensin‐converting enzyme 2 activity and plasma equilibrium concentrations of angiotensin peptides in dogs with heart disease,http://dx.doi.org/10.1111/jvim.15548,PMC6639469,31254308,CC BY-NC,"BACKGROUND: Angiotensin‐converting enzyme 2 (ACE2) is a homologue of angiotensin‐converting enzyme (ACE) and produces angiotensin peptides (APs), such as angiotensin 1‐9 and 1‐7 that are vasodilatory and natriuretic, and act to counterbalance angiotensin II. HYPOTHESIS: Evidence of ACE2 can be found in tissues and plasma of dogs. Equilibrium concentrations of renin angiotensin aldosterone system (RAAS) APs differ in dogs with heart disease compared to healthy dogs and recombinant human ACE2 (rhACE2) alters relative concentrations of APs. ANIMALS: Forty‐nine dogs with and 34 dogs without heart disease. METHODS: Immunohistochemistry and assays for tissue and plasma ACE2 activity and equilibrium concentrations of plasma RAAS APs were performed. RESULTS: Immunolabeling for ACE2 was present in kidney and myocardial tissue. Median plasma ACE2 activity was significantly increased in dogs with congestive heart failure (CHF; 6.9 mU/mg; interquartile range [IQR], 5.1‐12.1) as compared to control (2.2 mU/mg; IQR, 1.8‐3.0; P = .0003). Plasma equilibrium analysis of RAAS APs identified significant increases in the median concentrations of beneficial APs, such as angiotensin 1‐7, in dogs with CHF (486.7 pg/mL; IQR, 214.2‐1168) as compared to those with preclinical disease (41.0 pg/mL; IQR, 27.4‐45.1; P < .0001) or control (11.4 pg/mL; IQR, 7.1‐25.3; P = .01). Incubation of plasma samples from dogs with CHF with rhACE2 increased beneficial APs, such as angiotensin 1‐9 (preincubation, 10.3 pg/mL; IQR, 4.4‐37.2; postincubation, 2431 pg/mL; IQR, 1355‐3037; P = .02), while simultaneously decreasing maladaptive APs, such as angiotensin II (preincubation, 53.4 pg/mL; IQR, 28.6‐226.4; postincubation, 2.4 pg/mL; IQR, 0.50‐5.8; P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Recognition of the ACE2 system expands the conventional view of the RAAS in the dog and represents an important potential therapeutic target.",2019 Jun 28 Jul-Aug,"['Larouche‐Lebel, Éva', 'Loughran, Kerry A.', 'Oyama, Mark A.', 'Solter, Phil F.', 'Laughlin, Danielle S.', 'Sánchez, Melissa D.', 'Assenmacher, Charles‐Antoine', 'Fox, Philip R.', 'Fries, Ryan C.']",J Vet Intern Med,,,True
9095dbfa1951b433c4f02eab37fac3cd1f355169,PMC,Plasma and tissue angiotensin‐converting enzyme 2 activity and plasma equilibrium concentrations of angiotensin peptides in dogs with heart disease,http://dx.doi.org/10.1111/jvim.15548,PMC6639469,31254308,CC BY-NC,"BACKGROUND: Angiotensin‐converting enzyme 2 (ACE2) is a homologue of angiotensin‐converting enzyme (ACE) and produces angiotensin peptides (APs), such as angiotensin 1‐9 and 1‐7 that are vasodilatory and natriuretic, and act to counterbalance angiotensin II. HYPOTHESIS: Evidence of ACE2 can be found in tissues and plasma of dogs. Equilibrium concentrations of renin angiotensin aldosterone system (RAAS) APs differ in dogs with heart disease compared to healthy dogs and recombinant human ACE2 (rhACE2) alters relative concentrations of APs. ANIMALS: Forty‐nine dogs with and 34 dogs without heart disease. METHODS: Immunohistochemistry and assays for tissue and plasma ACE2 activity and equilibrium concentrations of plasma RAAS APs were performed. RESULTS: Immunolabeling for ACE2 was present in kidney and myocardial tissue. Median plasma ACE2 activity was significantly increased in dogs with congestive heart failure (CHF; 6.9 mU/mg; interquartile range [IQR], 5.1‐12.1) as compared to control (2.2 mU/mg; IQR, 1.8‐3.0; P = .0003). Plasma equilibrium analysis of RAAS APs identified significant increases in the median concentrations of beneficial APs, such as angiotensin 1‐7, in dogs with CHF (486.7 pg/mL; IQR, 214.2‐1168) as compared to those with preclinical disease (41.0 pg/mL; IQR, 27.4‐45.1; P < .0001) or control (11.4 pg/mL; IQR, 7.1‐25.3; P = .01). Incubation of plasma samples from dogs with CHF with rhACE2 increased beneficial APs, such as angiotensin 1‐9 (preincubation, 10.3 pg/mL; IQR, 4.4‐37.2; postincubation, 2431 pg/mL; IQR, 1355‐3037; P = .02), while simultaneously decreasing maladaptive APs, such as angiotensin II (preincubation, 53.4 pg/mL; IQR, 28.6‐226.4; postincubation, 2.4 pg/mL; IQR, 0.50‐5.8; P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Recognition of the ACE2 system expands the conventional view of the RAAS in the dog and represents an important potential therapeutic target.",2019 Jun 28 Jul-Aug,"['Larouche‐Lebel, Éva', 'Loughran, Kerry A.', 'Oyama, Mark A.', 'Solter, Phil F.', 'Laughlin, Danielle S.', 'Sánchez, Melissa D.', 'Assenmacher, Charles‐Antoine', 'Fox, Philip R.', 'Fries, Ryan C.']",J Vet Intern Med,,,False
656c938ecdcc9da033e96de658ac1673959e0f6e,PMC,Plasma and tissue angiotensin‐converting enzyme 2 activity and plasma equilibrium concentrations of angiotensin peptides in dogs with heart disease,http://dx.doi.org/10.1111/jvim.15548,PMC6639469,31254308,CC BY-NC,"BACKGROUND: Angiotensin‐converting enzyme 2 (ACE2) is a homologue of angiotensin‐converting enzyme (ACE) and produces angiotensin peptides (APs), such as angiotensin 1‐9 and 1‐7 that are vasodilatory and natriuretic, and act to counterbalance angiotensin II. HYPOTHESIS: Evidence of ACE2 can be found in tissues and plasma of dogs. Equilibrium concentrations of renin angiotensin aldosterone system (RAAS) APs differ in dogs with heart disease compared to healthy dogs and recombinant human ACE2 (rhACE2) alters relative concentrations of APs. ANIMALS: Forty‐nine dogs with and 34 dogs without heart disease. METHODS: Immunohistochemistry and assays for tissue and plasma ACE2 activity and equilibrium concentrations of plasma RAAS APs were performed. RESULTS: Immunolabeling for ACE2 was present in kidney and myocardial tissue. Median plasma ACE2 activity was significantly increased in dogs with congestive heart failure (CHF; 6.9 mU/mg; interquartile range [IQR], 5.1‐12.1) as compared to control (2.2 mU/mg; IQR, 1.8‐3.0; P = .0003). Plasma equilibrium analysis of RAAS APs identified significant increases in the median concentrations of beneficial APs, such as angiotensin 1‐7, in dogs with CHF (486.7 pg/mL; IQR, 214.2‐1168) as compared to those with preclinical disease (41.0 pg/mL; IQR, 27.4‐45.1; P < .0001) or control (11.4 pg/mL; IQR, 7.1‐25.3; P = .01). Incubation of plasma samples from dogs with CHF with rhACE2 increased beneficial APs, such as angiotensin 1‐9 (preincubation, 10.3 pg/mL; IQR, 4.4‐37.2; postincubation, 2431 pg/mL; IQR, 1355‐3037; P = .02), while simultaneously decreasing maladaptive APs, such as angiotensin II (preincubation, 53.4 pg/mL; IQR, 28.6‐226.4; postincubation, 2.4 pg/mL; IQR, 0.50‐5.8; P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Recognition of the ACE2 system expands the conventional view of the RAAS in the dog and represents an important potential therapeutic target.",2019 Jun 28 Jul-Aug,"['Larouche‐Lebel, Éva', 'Loughran, Kerry A.', 'Oyama, Mark A.', 'Solter, Phil F.', 'Laughlin, Danielle S.', 'Sánchez, Melissa D.', 'Assenmacher, Charles‐Antoine', 'Fox, Philip R.', 'Fries, Ryan C.']",J Vet Intern Med,,,False
9cc5e110d250f1c0f9fe64ba621c7bc300ddf58d,PMC,Plasma and tissue angiotensin‐converting enzyme 2 activity and plasma equilibrium concentrations of angiotensin peptides in dogs with heart disease,http://dx.doi.org/10.1111/jvim.15548,PMC6639469,31254308,CC BY-NC,"BACKGROUND: Angiotensin‐converting enzyme 2 (ACE2) is a homologue of angiotensin‐converting enzyme (ACE) and produces angiotensin peptides (APs), such as angiotensin 1‐9 and 1‐7 that are vasodilatory and natriuretic, and act to counterbalance angiotensin II. HYPOTHESIS: Evidence of ACE2 can be found in tissues and plasma of dogs. Equilibrium concentrations of renin angiotensin aldosterone system (RAAS) APs differ in dogs with heart disease compared to healthy dogs and recombinant human ACE2 (rhACE2) alters relative concentrations of APs. ANIMALS: Forty‐nine dogs with and 34 dogs without heart disease. METHODS: Immunohistochemistry and assays for tissue and plasma ACE2 activity and equilibrium concentrations of plasma RAAS APs were performed. RESULTS: Immunolabeling for ACE2 was present in kidney and myocardial tissue. Median plasma ACE2 activity was significantly increased in dogs with congestive heart failure (CHF; 6.9 mU/mg; interquartile range [IQR], 5.1‐12.1) as compared to control (2.2 mU/mg; IQR, 1.8‐3.0; P = .0003). Plasma equilibrium analysis of RAAS APs identified significant increases in the median concentrations of beneficial APs, such as angiotensin 1‐7, in dogs with CHF (486.7 pg/mL; IQR, 214.2‐1168) as compared to those with preclinical disease (41.0 pg/mL; IQR, 27.4‐45.1; P < .0001) or control (11.4 pg/mL; IQR, 7.1‐25.3; P = .01). Incubation of plasma samples from dogs with CHF with rhACE2 increased beneficial APs, such as angiotensin 1‐9 (preincubation, 10.3 pg/mL; IQR, 4.4‐37.2; postincubation, 2431 pg/mL; IQR, 1355‐3037; P = .02), while simultaneously decreasing maladaptive APs, such as angiotensin II (preincubation, 53.4 pg/mL; IQR, 28.6‐226.4; postincubation, 2.4 pg/mL; IQR, 0.50‐5.8; P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Recognition of the ACE2 system expands the conventional view of the RAAS in the dog and represents an important potential therapeutic target.",2019 Jun 28 Jul-Aug,"['Larouche‐Lebel, Éva', 'Loughran, Kerry A.', 'Oyama, Mark A.', 'Solter, Phil F.', 'Laughlin, Danielle S.', 'Sánchez, Melissa D.', 'Assenmacher, Charles‐Antoine', 'Fox, Philip R.', 'Fries, Ryan C.']",J Vet Intern Med,,,False
644c29fa7c611e8dbd689ff0cba3643c929835e2,PMC,Plasma and tissue angiotensin‐converting enzyme 2 activity and plasma equilibrium concentrations of angiotensin peptides in dogs with heart disease,http://dx.doi.org/10.1111/jvim.15548,PMC6639469,31254308,CC BY-NC,"BACKGROUND: Angiotensin‐converting enzyme 2 (ACE2) is a homologue of angiotensin‐converting enzyme (ACE) and produces angiotensin peptides (APs), such as angiotensin 1‐9 and 1‐7 that are vasodilatory and natriuretic, and act to counterbalance angiotensin II. HYPOTHESIS: Evidence of ACE2 can be found in tissues and plasma of dogs. Equilibrium concentrations of renin angiotensin aldosterone system (RAAS) APs differ in dogs with heart disease compared to healthy dogs and recombinant human ACE2 (rhACE2) alters relative concentrations of APs. ANIMALS: Forty‐nine dogs with and 34 dogs without heart disease. METHODS: Immunohistochemistry and assays for tissue and plasma ACE2 activity and equilibrium concentrations of plasma RAAS APs were performed. RESULTS: Immunolabeling for ACE2 was present in kidney and myocardial tissue. Median plasma ACE2 activity was significantly increased in dogs with congestive heart failure (CHF; 6.9 mU/mg; interquartile range [IQR], 5.1‐12.1) as compared to control (2.2 mU/mg; IQR, 1.8‐3.0; P = .0003). Plasma equilibrium analysis of RAAS APs identified significant increases in the median concentrations of beneficial APs, such as angiotensin 1‐7, in dogs with CHF (486.7 pg/mL; IQR, 214.2‐1168) as compared to those with preclinical disease (41.0 pg/mL; IQR, 27.4‐45.1; P < .0001) or control (11.4 pg/mL; IQR, 7.1‐25.3; P = .01). Incubation of plasma samples from dogs with CHF with rhACE2 increased beneficial APs, such as angiotensin 1‐9 (preincubation, 10.3 pg/mL; IQR, 4.4‐37.2; postincubation, 2431 pg/mL; IQR, 1355‐3037; P = .02), while simultaneously decreasing maladaptive APs, such as angiotensin II (preincubation, 53.4 pg/mL; IQR, 28.6‐226.4; postincubation, 2.4 pg/mL; IQR, 0.50‐5.8; P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Recognition of the ACE2 system expands the conventional view of the RAAS in the dog and represents an important potential therapeutic target.",2019 Jun 28 Jul-Aug,"['Larouche‐Lebel, Éva', 'Loughran, Kerry A.', 'Oyama, Mark A.', 'Solter, Phil F.', 'Laughlin, Danielle S.', 'Sánchez, Melissa D.', 'Assenmacher, Charles‐Antoine', 'Fox, Philip R.', 'Fries, Ryan C.']",J Vet Intern Med,,,False
24bc853dce27cbe938ca42aefdaa4e788df30481,PMC,Exploratory cohort study to determine if dry cow vaccination with a Salmonella Newport bacterin can protect dairy calves against oral Salmonella challenge,http://dx.doi.org/10.1111/jvim.15529,PMC6639490,31134697,CC BY-NC,"BACKGROUND: Salmonellosis is a major cause of morbidity and mortality in neonatal calves, often occurring before preventative vaccines can be administered. HYPOTHESIS/OBJECTIVE: To evaluate the protective effect on calves of colostrum from cows vaccinated with a commercially available Salmonella Newport bacterin against a Salmonella Typhimurium challenge. ANIMALS: Twenty Holstein bull calves from a university dairy farm. METHODS: Nonrandomized placebo‐controlled trial in which colostrum was harvested from 30 cows that received 2 doses of either Salmonella bacterin or saline before calving. Colostrum collected from each group was pooled and fed to 2 groups of 10 calves at birth. At approximately 2 weeks of age, calves were challenged with Salmonella Typhimurium. Clinical, hematologic, microbiological, and postmortem findings were compared between the 2 groups. RESULTS: No differences in mortality, clinical findings, hematology results, blood and fecal cultures, or necropsy findings between the 2 groups were observed. Vaccinated cows had higher colostral titers, and calves fed this colostrum had higher serum titers (mean difference, 0.429; mean [SE], 0.852 [0.02] for vaccinated versus 0.423 [0.02] for control calves). CONCLUSIONS AND CLINICAL IMPORTANCE: Transfer of colostral immunoglobulins from Salmonella enterica serotype Newport bacterin to neonatal calves was not sufficient to decrease mortality, clinical signs, sepsis, intestinal damage, or fecal shedding when exposed to a highly pathogenic Salmonella isolate. A large‐scale randomized controlled clinical trial is needed to evaluate the efficacy of this bacterin when administered in the dry period for prevention of salmonellosis in neonatal calves.",2019 May 27 Jul-Aug,"['Foster, Derek', 'Jacob, Megan', 'Stowe, Devorah', 'Smith, Geof']",J Vet Intern Med,,,True
8ec28590f496ed0fda704679a0b69f03c1d9e539,PMC,Exploratory cohort study to determine if dry cow vaccination with a Salmonella Newport bacterin can protect dairy calves against oral Salmonella challenge,http://dx.doi.org/10.1111/jvim.15529,PMC6639490,31134697,CC BY-NC,"BACKGROUND: Salmonellosis is a major cause of morbidity and mortality in neonatal calves, often occurring before preventative vaccines can be administered. HYPOTHESIS/OBJECTIVE: To evaluate the protective effect on calves of colostrum from cows vaccinated with a commercially available Salmonella Newport bacterin against a Salmonella Typhimurium challenge. ANIMALS: Twenty Holstein bull calves from a university dairy farm. METHODS: Nonrandomized placebo‐controlled trial in which colostrum was harvested from 30 cows that received 2 doses of either Salmonella bacterin or saline before calving. Colostrum collected from each group was pooled and fed to 2 groups of 10 calves at birth. At approximately 2 weeks of age, calves were challenged with Salmonella Typhimurium. Clinical, hematologic, microbiological, and postmortem findings were compared between the 2 groups. RESULTS: No differences in mortality, clinical findings, hematology results, blood and fecal cultures, or necropsy findings between the 2 groups were observed. Vaccinated cows had higher colostral titers, and calves fed this colostrum had higher serum titers (mean difference, 0.429; mean [SE], 0.852 [0.02] for vaccinated versus 0.423 [0.02] for control calves). CONCLUSIONS AND CLINICAL IMPORTANCE: Transfer of colostral immunoglobulins from Salmonella enterica serotype Newport bacterin to neonatal calves was not sufficient to decrease mortality, clinical signs, sepsis, intestinal damage, or fecal shedding when exposed to a highly pathogenic Salmonella isolate. A large‐scale randomized controlled clinical trial is needed to evaluate the efficacy of this bacterin when administered in the dry period for prevention of salmonellosis in neonatal calves.",2019 May 27 Jul-Aug,"['Foster, Derek', 'Jacob, Megan', 'Stowe, Devorah', 'Smith, Geof']",J Vet Intern Med,,,False
29ead3f1e4f24c9158b65d37a4ba9d839fb9028c,PMC,Randomized controlled clinical trial on the effect of oral immunoglobulin supplementation on neonatal dairy calves with diarrhea,http://dx.doi.org/10.1111/jvim.15538,PMC6639563,31124588,CC BY-NC,"BACKGROUND: Nonantibiotic alternatives providing local gut immunity have been recommended for managing calf diarrhea. ANIMALS: One hundred and two calves with diarrhea. HYPOTHESIS: Oral supplementation with immunoglobulins in calves with diarrhea will reduce time to resolution of diarrhea, number of treatment events, and mortality rate. METHODS: Randomized controlled trial. Calves were assigned into 1 of 3 groups. The treatment group was supplemented with 20 g of immunoglobulins in milk twice daily for 14 days. The placebo group was supplemented with 20 g of a product with similar nutritional value as the treatment group, but without immunoglobulins, in milk, twice daily for 14 days. The control group received no supplements. Medical treatments, time to resolution of diarrhea, and case fatality rates were compared. RESULTS: There was no difference in the proportion of treatment events (treatment, 79% versus placebo, 77% versus control, 71%) among groups (P = .69). The median time to resolution of diarrhea was not different between the treatment (10.5 days; 95% confidence interval [CI], 7, 13) and control (8 days; 95% CI, 5, 10) groups (P = .08) or between the placebo (6.5 days; 95% CI, 3, 9) and control groups (P = .89). Median time to resolution was shorter (P = .008) in the placebo compared to the treatment group (6.5 versus 10.5 days). Case fatality rates among groups (treatment, 12% versus placebo, 3% versus control, 3%) were not different (P = .36). CONCLUSIONS AND CLINICAL IMPORTANCE: Expected benefits of conferring local gut immunity by immunoglobulin supplementation in calves with diarrhea were not evident.",2019 May 24 Jul-Aug,"['Chung, James J.', 'Rayburn, Maire C.', 'Chigerwe, Munashe']",J Vet Intern Med,,,True
c98075a839f10763a8c30207b33c57e4455bc4ae,PMC,Non-lytic antibiotic treatment in community-acquired pneumococcal pneumonia does not attenuate inflammation: the PRISTINE trial,http://dx.doi.org/10.1093/jac/dkz207,PMC6640306,31106377,CC BY-NC,"BACKGROUND: The inflammatory response in pneumococcal infection is primarily driven by immunoreactive bacterial cell wall components [lipoteichoic acid (LTA)]. An acute release of these components occurs when pneumococcal infection is treated with β-lactam antibiotics. OBJECTIVES: We hypothesized that non-lytic rifampicin compared with lytic β-lactam antibiotic treatment would attenuate the inflammatory response in patients with pneumococcal pneumonia. METHODS: In the PRISTINE (Pneumonia treated with RIfampicin aTtenuates INflammation) trial, a randomized, therapeutic controlled, exploratory study in patients with community-acquired pneumococcal pneumonia, we looked at LTA release and inflammatory and clinical response during treatment with both rifampicin and β-lactam compared with treatment with β-lactam antibiotics only. The trial is registered in the Dutch trial registry, number NTR3751 (European Clinical Trials Database number 2012-003067-22). RESULTS: Forty-one patients with community-acquired pneumonia were included; 17 of them had pneumococcal pneumonia. LTA release, LTA-mediated inflammatory responses, clinical outcomes, inflammatory biomarkers and transcription profiles were not different between treatment groups. CONCLUSIONS: The PRISTINE study demonstrated the feasibility of adding rifampicin to β-lactam antibiotics in the treatment of community-acquired pneumococcal pneumonia, but, despite solid in vitro and experimental animal research evidence, failed to demonstrate a difference in plasma LTA concentrations and subsequent inflammatory and clinical responses. Most likely, an inhibitory effect of human plasma contributes to the low immune response in these patients. In addition, LTA plasma concentration could be too low to mount a response via Toll-like receptor 2 in vitro, but may nonetheless have an effect in vivo.",2019 Aug 18,"['Groeneveld, Geert H', 'van der Reyden, Tanny J', 'Joosten, Simone A', 'Bootsma, Hester J', 'Cobbaert, Christa M', 'de Vries, Jutte J C', 'Kuijper, Ed J', 'van Dissel, Jaap T']",J Antimicrob Chemother,,,True
cfd6678648c72749e498c81d8cfea523009d69d0,PMC,Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases,http://dx.doi.org/10.1016/j.ebiom.2019.06.036,PMC6642283,31257147,CC BY-NC-ND,"Duchenne muscular dystrophy (DMD) is an X-linked disorder characterized by progressive muscle degeneration, caused by the absence of dystrophin. Exon skipping by antisense oligonucleotides (ASOs) has recently gained recognition as therapeutic approach in DMD. Conjugation of a peptide to the phosphorodiamidate morpholino backbone (PMO) of ASOs generated the peptide-conjugated PMOs (PPMOs) that exhibit a dramatically improved pharmacokinetic profile. When tested in animal models, PPMOs demonstrate effective exon skipping in target muscles and prolonged duration of dystrophin restoration after a treatment regime. Herein we summarize the main pathophysiological features of DMD and the emergence of PPMOs as promising exon skipping agents aiming to rescue defective gene expression in DMD and other neuromuscular diseases. The listed PPMO laboratory findings correspond to latest trends in the field and highlight the obstacles that must be overcome prior to translating the animal-based research into clinical trials tailored to the needs of patients suffering from neuromuscular diseases.",2019 Jun 27,"['Tsoumpra, Maria K.', 'Fukumoto, Seiji', 'Matsumoto, Toshio', ""Takeda, Shin'ichi"", 'Wood, Matthew J.A.', 'Aoki, Yoshitsugu']",EBioMedicine,,,False
60f1455bed921da2e4f3df7aae854cb8e142ff44,PMC,Gain‐of‐function experiments with bacteriophage lambda uncover residues under diversifying selection in nature,http://dx.doi.org/10.1111/evo.13586,PMC6646904,30152871,CC BY-NC-ND,"Viral gain‐of‐function mutations frequently evolve during laboratory experiments. Whether the specific mutations that evolve in the lab also evolve in nature and whether they have the same impact on evolution in the real world is unknown. We studied a model virus, bacteriophage λ, that repeatedly evolves to exploit a new host receptor under typical laboratory conditions. Here, we demonstrate that two residues of λ’s J protein are required for the new function. In natural λ variants, these amino acid sites are highly diverse and evolve at high rates. Insertions and deletions at these locations are associated with phylogenetic patterns indicative of ecological diversification. Our results show that viral evolution in the laboratory mirrors that in nature and that laboratory experiments can be coupled with protein sequence analyses to identify the causes of viral evolution in the real world. Furthermore, our results provide evidence for widespread host‐shift evolution in lambdoid viruses.",2018 Oct 11,"['Maddamsetti, Rohan', 'Johnson, Daniel T.', 'Spielman, Stephanie J.', 'Petrie, Katherine L.', 'Marks, Debora S.', 'Meyer, Justin R.']",Evolution,,,True
45d421f19615b936de0527809bb71e12be89fa7c,PMC,"One-step triplex PCR/RT-PCR to detect canine distemper virus, canine parvovirus and canine kobuvirus",http://dx.doi.org/10.1292/jvms.17-0442,PMC6656820,29367517,CC BY-NC-ND,"To rapidly distinguish Canine distemper virus (CDV), canine parvovirus (CPV), and canine kobuvirus (CaKoV) in practice, a one-step multiplex PCR/RT-PCR assay was developed, with detection limits of 10(2.1) TCID(50) for CDV, 10(1.9) TCID(50) for CPV and 10(3) copies for CaKoV. This method did not amplify nonspecific DNA or RNA from other canine viruses. Therefore, the assay provides a sensitive tool for the rapid clinical detection and epidemiological surveillance of CDV, CPV and CaKoV in dogs.",2019 Jul 23,"['LIU, Dafei', 'LIU, Fei', 'GUO, Dongchun', 'HU, Xiaoliang', 'LI, Zhijie', 'LI, Zhigang', 'MA, Jianzhang', 'LIU, Chunguo']",J Vet Med Sci,,,True
7a819c63e6e9a3c1979c34b11e3866d23dbed476,PMC,Genes and Pathways Regulating Decline in Lung Function and Airway Remodeling in Asthma,http://dx.doi.org/10.4168/aair.2019.11.5.604,PMC6658410,31332973,CC BY-NC,"Asthma is a common disorder of the airways characterized by airway inflammation and by decline in lung function and airway remodeling in a subset of asthmatics. Airway remodeling is characterized by structural changes which include airway smooth muscle hypertrophy/hyperplasia, subepithelial fibrosis due to thickening of the reticular basement membrane, mucus metaplasia of the epithelium, and angiogenesis. Epidemiologic studies suggest that both genetic and environmental factors may contribute to decline in lung function and airway remodeling in a subset of asthmatics. Environmental factors include respiratory viral infection-triggered asthma exacerbations, and tobacco smoke. There is also evidence that several asthma candidate genes may contribute to decline in lung function, including ADAM33, PLAUR, VEGF, IL13, CHI3L1, TSLP, GSDMB, TGFB1, POSTN, ESR1 and ARG2. In addition, mediators or cytokines, including cysteinyl leukotrienes, matrix metallopeptidase-9, interleukin-33 and eosinophil expression of transforming growth factor-β, may contribute to airway remodeling in asthma. Although increased airway smooth muscle is associated with reduced lung function (i.e. forced expiratory volume in 1 second) in asthma, there have been few long-term studies to determine how individual pathologic features of airway remodeling contribute to decline in lung function in asthma. Clinical studies with inhibitors of individual gene products, cytokines or mediators are needed in asthmatic patients to identify their individual role in decline in lung function and/or airway remodeling.",2019 Jun 4,"['Hur, Gyu Young', 'Broide, David H.']",Allergy Asthma Immunol Res,,,True
725f0a6590f20c15be0ae719463c0624a34ee1af,PMC,Mechanism of Cxc Chemokine Ligand 5 (CXCL5)/Cxc Chemokine Receptor 2 (CXCR2) Bio-Axis in Mice with Acute Respiratory Distress Syndrome,http://dx.doi.org/10.12659/MSM.915835,PMC6659456,31311916,CC BY-NC-ND,"BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common acute and severe disease in clinic. Recent studies indicated that Cxc chemokine ligand 5 (CXCL5), an inflammatory chemokine, was associated with tumorigenesis. The present study investigated the role of the CXCL5/Cxc chemokine receptor 2 (CXCR2) bio-axis in ARDS, and explored the underlying molecular mechanism. MATERIAL/METHODS: The pathological morphology of lung tissue and degree of pulmonary edema were assessed by hematoxylin-eosin staining and pulmonary edema score, respectively. Real-time PCR and Western blot analysis were performed to detect the expression levels of CXCL5, CXCR2, Matrix metalloproteinases 2 (MMP2), and Matrix metalloproteinases 9 (MMP9) in lung tissues. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the expression levels of CXCL5 and inflammatory factors (IL-1β, IL-6, TNF-α, and IL-10) in serum. RESULTS: The results demonstrated that diffuse alveolar damage and pulmonary edema appeared in lipopolysaccharide (LPS)-induced ARDS and were positively correlated with the severity of ARDS. In addition, CXCL5 and its receptor CXCR2 were overexpressed by upregulation of MMP2 and MMP9 in lung tissues of ARDS. In addition, CXCL5 neutralizing antibody effectively alleviated inflammatory response, diffuse alveolar damage, and pulmonary edema, and decreased the expression levels of MMP2 and MMP9 compared to LPS-induced ARDS. CONCLUSIONS: We found that CXCL5/CXCR2 accelerated the progression of ARDS, partly by upregulation of MMP2 and MMP9 in lung tissues with the release of inflammatory factors.",2019 Jul 17,"['Wang, Chang-yong', 'Shang, Min', 'Zhou, Chen-liang', 'Feng, Li-zhi', 'Zhou, Qing-shan', 'Hu, Ke']",Med Sci Monit,,,True
c58195e4e9894fdbf2e89872912cd0fb46c9f947,PMC,Impact of the 2015 Middle East Respiratory Syndrome Outbreak on Emergency Care Utilization and Mortality in South Korea,http://dx.doi.org/10.3349/ymj.2019.60.8.796,PMC6660446,31347336,CC BY-NC,"PURPOSE: In May 2015, South Korea experienced an epidemic of Middle East respiratory syndrome (MERS). This study investigated the impacts of MERS epidemic on emergency care utilization and mortality in South Korea. MATERIALS AND METHODS: A natural experimental study was conducted using healthcare utilization and mortality data of the entire Korean population. The number of monthly emergency room (ER) visits was investigated to identify changes in emergency care utilization during the MERS epidemic; these trends were also examined according to patients' demographic factors, disease severity, and region. Deaths within 7 days after visiting an ER were analyzed to evaluate the impact of the reduction in ER visits on mortality. RESULTS: The number of ER visits during the peak of the MERS epidemic (June 2015) decreased by 33.1% compared to the average figures from June 2014 and June 2016. The decrease was observed in all age, sex, and income groups, and was more pronounced for low-acuity diseases (acute otitis media: 53.0%; upper respiratory infections: 45.2%) than for high-acuity diseases (myocardial infarctions: 14.0%; ischemic stroke: 16.6%). No substantial changes were detected for the highest-acuity diseases, with increases of 3.5% for cardiac arrest and 2.4% for hemorrhagic stroke. The number of deaths within 7 days of an ER visit did not change significantly. CONCLUSION: During the MERS epidemic, the number of ER visits decreased in all age, sex, and socioeconomic groups, and decreased most sharply for low-acuity diseases. Nonetheless, there was no significant change in deaths after emergency care.",2019 Aug 1,"['Lee, Sun Young', 'Khang, Young-Ho', 'Lim, Hwa-Kyung']",Yonsei Med J,,,True
f849989abfab9b3b932996b1f4189ab63f06d669,PMC,Impact of the 2015 Middle East Respiratory Syndrome Outbreak on Emergency Care Utilization and Mortality in South Korea,http://dx.doi.org/10.3349/ymj.2019.60.8.796,PMC6660446,31347336,CC BY-NC,"PURPOSE: In May 2015, South Korea experienced an epidemic of Middle East respiratory syndrome (MERS). This study investigated the impacts of MERS epidemic on emergency care utilization and mortality in South Korea. MATERIALS AND METHODS: A natural experimental study was conducted using healthcare utilization and mortality data of the entire Korean population. The number of monthly emergency room (ER) visits was investigated to identify changes in emergency care utilization during the MERS epidemic; these trends were also examined according to patients' demographic factors, disease severity, and region. Deaths within 7 days after visiting an ER were analyzed to evaluate the impact of the reduction in ER visits on mortality. RESULTS: The number of ER visits during the peak of the MERS epidemic (June 2015) decreased by 33.1% compared to the average figures from June 2014 and June 2016. The decrease was observed in all age, sex, and income groups, and was more pronounced for low-acuity diseases (acute otitis media: 53.0%; upper respiratory infections: 45.2%) than for high-acuity diseases (myocardial infarctions: 14.0%; ischemic stroke: 16.6%). No substantial changes were detected for the highest-acuity diseases, with increases of 3.5% for cardiac arrest and 2.4% for hemorrhagic stroke. The number of deaths within 7 days of an ER visit did not change significantly. CONCLUSION: During the MERS epidemic, the number of ER visits decreased in all age, sex, and socioeconomic groups, and decreased most sharply for low-acuity diseases. Nonetheless, there was no significant change in deaths after emergency care.",2019 Aug 1,"['Lee, Sun Young', 'Khang, Young-Ho', 'Lim, Hwa-Kyung']",Yonsei Med J,,,False
14ca763ec476b15068c2475d3d495b23c019664c,PMC,Impact of the 2015 Middle East Respiratory Syndrome Outbreak on Emergency Care Utilization and Mortality in South Korea,http://dx.doi.org/10.3349/ymj.2019.60.8.796,PMC6660446,31347336,CC BY-NC,"PURPOSE: In May 2015, South Korea experienced an epidemic of Middle East respiratory syndrome (MERS). This study investigated the impacts of MERS epidemic on emergency care utilization and mortality in South Korea. MATERIALS AND METHODS: A natural experimental study was conducted using healthcare utilization and mortality data of the entire Korean population. The number of monthly emergency room (ER) visits was investigated to identify changes in emergency care utilization during the MERS epidemic; these trends were also examined according to patients' demographic factors, disease severity, and region. Deaths within 7 days after visiting an ER were analyzed to evaluate the impact of the reduction in ER visits on mortality. RESULTS: The number of ER visits during the peak of the MERS epidemic (June 2015) decreased by 33.1% compared to the average figures from June 2014 and June 2016. The decrease was observed in all age, sex, and income groups, and was more pronounced for low-acuity diseases (acute otitis media: 53.0%; upper respiratory infections: 45.2%) than for high-acuity diseases (myocardial infarctions: 14.0%; ischemic stroke: 16.6%). No substantial changes were detected for the highest-acuity diseases, with increases of 3.5% for cardiac arrest and 2.4% for hemorrhagic stroke. The number of deaths within 7 days of an ER visit did not change significantly. CONCLUSION: During the MERS epidemic, the number of ER visits decreased in all age, sex, and socioeconomic groups, and decreased most sharply for low-acuity diseases. Nonetheless, there was no significant change in deaths after emergency care.",2019 Aug 1,"['Lee, Sun Young', 'Khang, Young-Ho', 'Lim, Hwa-Kyung']",Yonsei Med J,,,False
326a5a610d778f8f3608045d4ca4f69b30e7204b,PMC,Impact of the 2015 Middle East Respiratory Syndrome Outbreak on Emergency Care Utilization and Mortality in South Korea,http://dx.doi.org/10.3349/ymj.2019.60.8.796,PMC6660446,31347336,CC BY-NC,"PURPOSE: In May 2015, South Korea experienced an epidemic of Middle East respiratory syndrome (MERS). This study investigated the impacts of MERS epidemic on emergency care utilization and mortality in South Korea. MATERIALS AND METHODS: A natural experimental study was conducted using healthcare utilization and mortality data of the entire Korean population. The number of monthly emergency room (ER) visits was investigated to identify changes in emergency care utilization during the MERS epidemic; these trends were also examined according to patients' demographic factors, disease severity, and region. Deaths within 7 days after visiting an ER were analyzed to evaluate the impact of the reduction in ER visits on mortality. RESULTS: The number of ER visits during the peak of the MERS epidemic (June 2015) decreased by 33.1% compared to the average figures from June 2014 and June 2016. The decrease was observed in all age, sex, and income groups, and was more pronounced for low-acuity diseases (acute otitis media: 53.0%; upper respiratory infections: 45.2%) than for high-acuity diseases (myocardial infarctions: 14.0%; ischemic stroke: 16.6%). No substantial changes were detected for the highest-acuity diseases, with increases of 3.5% for cardiac arrest and 2.4% for hemorrhagic stroke. The number of deaths within 7 days of an ER visit did not change significantly. CONCLUSION: During the MERS epidemic, the number of ER visits decreased in all age, sex, and socioeconomic groups, and decreased most sharply for low-acuity diseases. Nonetheless, there was no significant change in deaths after emergency care.",2019 Aug 1,"['Lee, Sun Young', 'Khang, Young-Ho', 'Lim, Hwa-Kyung']",Yonsei Med J,,,False
93c4cab815143b6a3d7de870bc238749cb1a1bfc,PMC,Impact of the 2015 Middle East Respiratory Syndrome Outbreak on Emergency Care Utilization and Mortality in South Korea,http://dx.doi.org/10.3349/ymj.2019.60.8.796,PMC6660446,31347336,CC BY-NC,"PURPOSE: In May 2015, South Korea experienced an epidemic of Middle East respiratory syndrome (MERS). This study investigated the impacts of MERS epidemic on emergency care utilization and mortality in South Korea. MATERIALS AND METHODS: A natural experimental study was conducted using healthcare utilization and mortality data of the entire Korean population. The number of monthly emergency room (ER) visits was investigated to identify changes in emergency care utilization during the MERS epidemic; these trends were also examined according to patients' demographic factors, disease severity, and region. Deaths within 7 days after visiting an ER were analyzed to evaluate the impact of the reduction in ER visits on mortality. RESULTS: The number of ER visits during the peak of the MERS epidemic (June 2015) decreased by 33.1% compared to the average figures from June 2014 and June 2016. The decrease was observed in all age, sex, and income groups, and was more pronounced for low-acuity diseases (acute otitis media: 53.0%; upper respiratory infections: 45.2%) than for high-acuity diseases (myocardial infarctions: 14.0%; ischemic stroke: 16.6%). No substantial changes were detected for the highest-acuity diseases, with increases of 3.5% for cardiac arrest and 2.4% for hemorrhagic stroke. The number of deaths within 7 days of an ER visit did not change significantly. CONCLUSION: During the MERS epidemic, the number of ER visits decreased in all age, sex, and socioeconomic groups, and decreased most sharply for low-acuity diseases. Nonetheless, there was no significant change in deaths after emergency care.",2019 Aug 1,"['Lee, Sun Young', 'Khang, Young-Ho', 'Lim, Hwa-Kyung']",Yonsei Med J,,,False
d7b842b943340f6143c4e44c899f76f8d517aa2b,PMC,Impact of the 2015 Middle East Respiratory Syndrome Outbreak on Emergency Care Utilization and Mortality in South Korea,http://dx.doi.org/10.3349/ymj.2019.60.8.796,PMC6660446,31347336,CC BY-NC,"PURPOSE: In May 2015, South Korea experienced an epidemic of Middle East respiratory syndrome (MERS). This study investigated the impacts of MERS epidemic on emergency care utilization and mortality in South Korea. MATERIALS AND METHODS: A natural experimental study was conducted using healthcare utilization and mortality data of the entire Korean population. The number of monthly emergency room (ER) visits was investigated to identify changes in emergency care utilization during the MERS epidemic; these trends were also examined according to patients' demographic factors, disease severity, and region. Deaths within 7 days after visiting an ER were analyzed to evaluate the impact of the reduction in ER visits on mortality. RESULTS: The number of ER visits during the peak of the MERS epidemic (June 2015) decreased by 33.1% compared to the average figures from June 2014 and June 2016. The decrease was observed in all age, sex, and income groups, and was more pronounced for low-acuity diseases (acute otitis media: 53.0%; upper respiratory infections: 45.2%) than for high-acuity diseases (myocardial infarctions: 14.0%; ischemic stroke: 16.6%). No substantial changes were detected for the highest-acuity diseases, with increases of 3.5% for cardiac arrest and 2.4% for hemorrhagic stroke. The number of deaths within 7 days of an ER visit did not change significantly. CONCLUSION: During the MERS epidemic, the number of ER visits decreased in all age, sex, and socioeconomic groups, and decreased most sharply for low-acuity diseases. Nonetheless, there was no significant change in deaths after emergency care.",2019 Aug 1,"['Lee, Sun Young', 'Khang, Young-Ho', 'Lim, Hwa-Kyung']",Yonsei Med J,,,False
e400bf79de752ad6ef0811e6dcce76a963ed09d2,PMC,Impact of the 2015 Middle East Respiratory Syndrome Outbreak on Emergency Care Utilization and Mortality in South Korea,http://dx.doi.org/10.3349/ymj.2019.60.8.796,PMC6660446,31347336,CC BY-NC,"PURPOSE: In May 2015, South Korea experienced an epidemic of Middle East respiratory syndrome (MERS). This study investigated the impacts of MERS epidemic on emergency care utilization and mortality in South Korea. MATERIALS AND METHODS: A natural experimental study was conducted using healthcare utilization and mortality data of the entire Korean population. The number of monthly emergency room (ER) visits was investigated to identify changes in emergency care utilization during the MERS epidemic; these trends were also examined according to patients' demographic factors, disease severity, and region. Deaths within 7 days after visiting an ER were analyzed to evaluate the impact of the reduction in ER visits on mortality. RESULTS: The number of ER visits during the peak of the MERS epidemic (June 2015) decreased by 33.1% compared to the average figures from June 2014 and June 2016. The decrease was observed in all age, sex, and income groups, and was more pronounced for low-acuity diseases (acute otitis media: 53.0%; upper respiratory infections: 45.2%) than for high-acuity diseases (myocardial infarctions: 14.0%; ischemic stroke: 16.6%). No substantial changes were detected for the highest-acuity diseases, with increases of 3.5% for cardiac arrest and 2.4% for hemorrhagic stroke. The number of deaths within 7 days of an ER visit did not change significantly. CONCLUSION: During the MERS epidemic, the number of ER visits decreased in all age, sex, and socioeconomic groups, and decreased most sharply for low-acuity diseases. Nonetheless, there was no significant change in deaths after emergency care.",2019 Aug 1,"['Lee, Sun Young', 'Khang, Young-Ho', 'Lim, Hwa-Kyung']",Yonsei Med J,,,False
c15a612b305f3a174a6f69c0ec4de0dd85afb646,PMC,Impact of the 2015 Middle East Respiratory Syndrome Outbreak on Emergency Care Utilization and Mortality in South Korea,http://dx.doi.org/10.3349/ymj.2019.60.8.796,PMC6660446,31347336,CC BY-NC,"PURPOSE: In May 2015, South Korea experienced an epidemic of Middle East respiratory syndrome (MERS). This study investigated the impacts of MERS epidemic on emergency care utilization and mortality in South Korea. MATERIALS AND METHODS: A natural experimental study was conducted using healthcare utilization and mortality data of the entire Korean population. The number of monthly emergency room (ER) visits was investigated to identify changes in emergency care utilization during the MERS epidemic; these trends were also examined according to patients' demographic factors, disease severity, and region. Deaths within 7 days after visiting an ER were analyzed to evaluate the impact of the reduction in ER visits on mortality. RESULTS: The number of ER visits during the peak of the MERS epidemic (June 2015) decreased by 33.1% compared to the average figures from June 2014 and June 2016. The decrease was observed in all age, sex, and income groups, and was more pronounced for low-acuity diseases (acute otitis media: 53.0%; upper respiratory infections: 45.2%) than for high-acuity diseases (myocardial infarctions: 14.0%; ischemic stroke: 16.6%). No substantial changes were detected for the highest-acuity diseases, with increases of 3.5% for cardiac arrest and 2.4% for hemorrhagic stroke. The number of deaths within 7 days of an ER visit did not change significantly. CONCLUSION: During the MERS epidemic, the number of ER visits decreased in all age, sex, and socioeconomic groups, and decreased most sharply for low-acuity diseases. Nonetheless, there was no significant change in deaths after emergency care.",2019 Aug 1,"['Lee, Sun Young', 'Khang, Young-Ho', 'Lim, Hwa-Kyung']",Yonsei Med J,,,True
1ce4231aeefd5ac1caef8246df9984b7455d16df,PMC,Impact of the 2015 Middle East Respiratory Syndrome Outbreak on Emergency Care Utilization and Mortality in South Korea,http://dx.doi.org/10.3349/ymj.2019.60.8.796,PMC6660446,31347336,CC BY-NC,"PURPOSE: In May 2015, South Korea experienced an epidemic of Middle East respiratory syndrome (MERS). This study investigated the impacts of MERS epidemic on emergency care utilization and mortality in South Korea. MATERIALS AND METHODS: A natural experimental study was conducted using healthcare utilization and mortality data of the entire Korean population. The number of monthly emergency room (ER) visits was investigated to identify changes in emergency care utilization during the MERS epidemic; these trends were also examined according to patients' demographic factors, disease severity, and region. Deaths within 7 days after visiting an ER were analyzed to evaluate the impact of the reduction in ER visits on mortality. RESULTS: The number of ER visits during the peak of the MERS epidemic (June 2015) decreased by 33.1% compared to the average figures from June 2014 and June 2016. The decrease was observed in all age, sex, and income groups, and was more pronounced for low-acuity diseases (acute otitis media: 53.0%; upper respiratory infections: 45.2%) than for high-acuity diseases (myocardial infarctions: 14.0%; ischemic stroke: 16.6%). No substantial changes were detected for the highest-acuity diseases, with increases of 3.5% for cardiac arrest and 2.4% for hemorrhagic stroke. The number of deaths within 7 days of an ER visit did not change significantly. CONCLUSION: During the MERS epidemic, the number of ER visits decreased in all age, sex, and socioeconomic groups, and decreased most sharply for low-acuity diseases. Nonetheless, there was no significant change in deaths after emergency care.",2019 Aug 1,"['Lee, Sun Young', 'Khang, Young-Ho', 'Lim, Hwa-Kyung']",Yonsei Med J,,,True
d660c08a826fd9d229644e55a130fd1614e3b3f6,PMC,Impact of the 2015 Middle East Respiratory Syndrome Outbreak on Emergency Care Utilization and Mortality in South Korea,http://dx.doi.org/10.3349/ymj.2019.60.8.796,PMC6660446,31347336,CC BY-NC,"PURPOSE: In May 2015, South Korea experienced an epidemic of Middle East respiratory syndrome (MERS). This study investigated the impacts of MERS epidemic on emergency care utilization and mortality in South Korea. MATERIALS AND METHODS: A natural experimental study was conducted using healthcare utilization and mortality data of the entire Korean population. The number of monthly emergency room (ER) visits was investigated to identify changes in emergency care utilization during the MERS epidemic; these trends were also examined according to patients' demographic factors, disease severity, and region. Deaths within 7 days after visiting an ER were analyzed to evaluate the impact of the reduction in ER visits on mortality. RESULTS: The number of ER visits during the peak of the MERS epidemic (June 2015) decreased by 33.1% compared to the average figures from June 2014 and June 2016. The decrease was observed in all age, sex, and income groups, and was more pronounced for low-acuity diseases (acute otitis media: 53.0%; upper respiratory infections: 45.2%) than for high-acuity diseases (myocardial infarctions: 14.0%; ischemic stroke: 16.6%). No substantial changes were detected for the highest-acuity diseases, with increases of 3.5% for cardiac arrest and 2.4% for hemorrhagic stroke. The number of deaths within 7 days of an ER visit did not change significantly. CONCLUSION: During the MERS epidemic, the number of ER visits decreased in all age, sex, and socioeconomic groups, and decreased most sharply for low-acuity diseases. Nonetheless, there was no significant change in deaths after emergency care.",2019 Aug 1,"['Lee, Sun Young', 'Khang, Young-Ho', 'Lim, Hwa-Kyung']",Yonsei Med J,,,False
b0419b7772c75f4f70ca0394ed3fede136025e5e,PMC,Impact of the 2015 Middle East Respiratory Syndrome Outbreak on Emergency Care Utilization and Mortality in South Korea,http://dx.doi.org/10.3349/ymj.2019.60.8.796,PMC6660446,31347336,CC BY-NC,"PURPOSE: In May 2015, South Korea experienced an epidemic of Middle East respiratory syndrome (MERS). This study investigated the impacts of MERS epidemic on emergency care utilization and mortality in South Korea. MATERIALS AND METHODS: A natural experimental study was conducted using healthcare utilization and mortality data of the entire Korean population. The number of monthly emergency room (ER) visits was investigated to identify changes in emergency care utilization during the MERS epidemic; these trends were also examined according to patients' demographic factors, disease severity, and region. Deaths within 7 days after visiting an ER were analyzed to evaluate the impact of the reduction in ER visits on mortality. RESULTS: The number of ER visits during the peak of the MERS epidemic (June 2015) decreased by 33.1% compared to the average figures from June 2014 and June 2016. The decrease was observed in all age, sex, and income groups, and was more pronounced for low-acuity diseases (acute otitis media: 53.0%; upper respiratory infections: 45.2%) than for high-acuity diseases (myocardial infarctions: 14.0%; ischemic stroke: 16.6%). No substantial changes were detected for the highest-acuity diseases, with increases of 3.5% for cardiac arrest and 2.4% for hemorrhagic stroke. The number of deaths within 7 days of an ER visit did not change significantly. CONCLUSION: During the MERS epidemic, the number of ER visits decreased in all age, sex, and socioeconomic groups, and decreased most sharply for low-acuity diseases. Nonetheless, there was no significant change in deaths after emergency care.",2019 Aug 1,"['Lee, Sun Young', 'Khang, Young-Ho', 'Lim, Hwa-Kyung']",Yonsei Med J,,,False
32d98992b213139fc36d2ff05af879b112e230f6,PMC,Severe Immune Thrombocytopenia Complicated by Intracerebral Haemorrhage Associated with Coronavirus Infection: A Case Report and Literature Review,http://dx.doi.org/10.12890/2019_001155,PMC6663043,31410357,CC BY-NC,"Immune thrombocytopenic purpura (ITP) is an autoimmune disorder that causes isolated thrombocytopenia. Many viruses have been identified as triggering the autoimmune process, including HIV, MCV, EBV, parvovirus, rubella and measles. However, ITP in association with coronavirus infection has not previously been reported. We describe the case of a healthy man who presented with severe ITP complicated by intracranial haemorrhage following upper respiratory tract infection. An infection screen revealed coronavirus infection. LEARNING POINTS: Coronavirus can cause severe immune thrombocytopenic purpura (ITP). Intracerebral haemorrhage is an uncommon presentation of ITP. Intravenous immunoglobulin and steroids are very effective treatments for severe ITP.",2019 Jul 12,"['Magdi, Mohamed', 'Rahil, Ali']",Eur J Case Rep Intern Med,,,True
e60a7630d751366b6ea36f9c0b60eed8e20a00f6,PMC,Rotavirus vaccine efficacy: current status and areas for improvement,http://dx.doi.org/10.1080/21645515.2018.1520583,PMC6663136,30215578,CC BY-NC-ND,"The difference noted in Rotavirus vaccine efficiency between high and low income countries correlates with the lack of universal access to clean water and higher standards of hygiene. Overcoming these obstacles will require great investment and also time, therefore more effective vaccines should be developed to meet the needs of those who would benefit the most from them. Increasing our current knowledge of mucosal immunity, response to Rotavirus infection and its modulation by circadian rhythms could point at actionable pathways to improve vaccination efficacy, especially in the case of individuals affected by environmental enteropathy. Also, a better understanding and validation of Rotavirus entry factors as well as the systematic monitoring of dominant strains could assist in tailoring vaccines to individual’s needs. Another aspect that could improve vaccine efficiency is targeting to M cells, for which new ligands could potentially be sought. Finally, alternative mucosal adjuvants and vaccine expression, storage and delivery systems could have a positive impact in the outcome of Rotavirus vaccination.",2018 Sep 19,"['Carvalho, Miguel F.', 'Gill, Davinder']",Hum Vaccin Immunother,,,True
a4e3ea0a718f906e5f879917d26384c2c0c49d09,PMC,"”For this one, let me take the risk”: why surgical staff continued to perform caesarean sections during the 2014–2016 Ebola epidemic in Sierra Leone",http://dx.doi.org/10.1136/bmjgh-2018-001361,PMC6666802,31406584,CC BY-NC,"INTRODUCTION: Routine health service provision decreased during the 2014–2016 Ebola virus disease (EVD) outbreak in Sierra Leone, while caesarean section (CS) rates at public hospitals did not. It is unknown what made staff provide CS despite the risks of contracting EVD. This study explores Sierra Leonean health worker perspectives of why they continued to provide CS. METHODS: This qualitative study documents the experiences of 15 CS providers who worked during the EVD outbreak. We interviewed surgical and non-surgical CS providers who worked at public hospitals that either increased or decreased CS volumes during the outbreak. Hospitals in all four administrative areas of Sierra Leone were included. Semistructured interviews averaged 97 min and healthcare experience 21 years. Transcripts were analysed by modified framework analysis in the NVivo V.11.4.1 software. RESULTS: We identified two themes that may explain why providers performed CS despite EVD risks: (1) clinical adaptability and (2) overcoming the moral dilemmas. CS providers reported being overworked and exposed to infection hazards. However, they developed clinical workarounds to the lack of surgical materials, protective equipment and standard operating procedures until the broader international response introduced formal personal protective equipment and infection prevention and control practices. CS providers reported that dutifulness and sense of responsibility for one’s community increased during EVD, which helped them justify taking the risk of being infected. Although most surgical activities were reduced to minimise staff exposure to EVD, staff at public hospitals tended to prioritise performing CS surgery for women with acute obstetric complications. CONCLUSION: This study found that CS surgery during EVD in Sierra Leone may be explained by remarkable decisions by individual CS providers at public hospitals. They adapted practically to material limitations exacerbated by the outbreak and overcame the moral dilemmas of performing CS despite the risk of being infected with EVD.",2019 Jul 19,"['Drevin, Gustaf', 'Mölsted Alvesson, Helle', 'van Duinen, Alex', 'Bolkan, Håkon A', 'Koroma, Alimamy P', 'Von Schreeb, Johan']",BMJ Glob Health,,,True
4f8881d84a2dc68828437d1778e841a3fbf6e2b4,PMC,"”For this one, let me take the risk”: why surgical staff continued to perform caesarean sections during the 2014–2016 Ebola epidemic in Sierra Leone",http://dx.doi.org/10.1136/bmjgh-2018-001361,PMC6666802,31406584,CC BY-NC,"INTRODUCTION: Routine health service provision decreased during the 2014–2016 Ebola virus disease (EVD) outbreak in Sierra Leone, while caesarean section (CS) rates at public hospitals did not. It is unknown what made staff provide CS despite the risks of contracting EVD. This study explores Sierra Leonean health worker perspectives of why they continued to provide CS. METHODS: This qualitative study documents the experiences of 15 CS providers who worked during the EVD outbreak. We interviewed surgical and non-surgical CS providers who worked at public hospitals that either increased or decreased CS volumes during the outbreak. Hospitals in all four administrative areas of Sierra Leone were included. Semistructured interviews averaged 97 min and healthcare experience 21 years. Transcripts were analysed by modified framework analysis in the NVivo V.11.4.1 software. RESULTS: We identified two themes that may explain why providers performed CS despite EVD risks: (1) clinical adaptability and (2) overcoming the moral dilemmas. CS providers reported being overworked and exposed to infection hazards. However, they developed clinical workarounds to the lack of surgical materials, protective equipment and standard operating procedures until the broader international response introduced formal personal protective equipment and infection prevention and control practices. CS providers reported that dutifulness and sense of responsibility for one’s community increased during EVD, which helped them justify taking the risk of being infected. Although most surgical activities were reduced to minimise staff exposure to EVD, staff at public hospitals tended to prioritise performing CS surgery for women with acute obstetric complications. CONCLUSION: This study found that CS surgery during EVD in Sierra Leone may be explained by remarkable decisions by individual CS providers at public hospitals. They adapted practically to material limitations exacerbated by the outbreak and overcame the moral dilemmas of performing CS despite the risk of being infected with EVD.",2019 Jul 19,"['Drevin, Gustaf', 'Mölsted Alvesson, Helle', 'van Duinen, Alex', 'Bolkan, Håkon A', 'Koroma, Alimamy P', 'Von Schreeb, Johan']",BMJ Glob Health,,,True
c10c2ab655bb4dccdba2f6271fd112ab40a52f6b,PMC,"”For this one, let me take the risk”: why surgical staff continued to perform caesarean sections during the 2014–2016 Ebola epidemic in Sierra Leone",http://dx.doi.org/10.1136/bmjgh-2018-001361,PMC6666802,31406584,CC BY-NC,"INTRODUCTION: Routine health service provision decreased during the 2014–2016 Ebola virus disease (EVD) outbreak in Sierra Leone, while caesarean section (CS) rates at public hospitals did not. It is unknown what made staff provide CS despite the risks of contracting EVD. This study explores Sierra Leonean health worker perspectives of why they continued to provide CS. METHODS: This qualitative study documents the experiences of 15 CS providers who worked during the EVD outbreak. We interviewed surgical and non-surgical CS providers who worked at public hospitals that either increased or decreased CS volumes during the outbreak. Hospitals in all four administrative areas of Sierra Leone were included. Semistructured interviews averaged 97 min and healthcare experience 21 years. Transcripts were analysed by modified framework analysis in the NVivo V.11.4.1 software. RESULTS: We identified two themes that may explain why providers performed CS despite EVD risks: (1) clinical adaptability and (2) overcoming the moral dilemmas. CS providers reported being overworked and exposed to infection hazards. However, they developed clinical workarounds to the lack of surgical materials, protective equipment and standard operating procedures until the broader international response introduced formal personal protective equipment and infection prevention and control practices. CS providers reported that dutifulness and sense of responsibility for one’s community increased during EVD, which helped them justify taking the risk of being infected. Although most surgical activities were reduced to minimise staff exposure to EVD, staff at public hospitals tended to prioritise performing CS surgery for women with acute obstetric complications. CONCLUSION: This study found that CS surgery during EVD in Sierra Leone may be explained by remarkable decisions by individual CS providers at public hospitals. They adapted practically to material limitations exacerbated by the outbreak and overcame the moral dilemmas of performing CS despite the risk of being infected with EVD.",2019 Jul 19,"['Drevin, Gustaf', 'Mölsted Alvesson, Helle', 'van Duinen, Alex', 'Bolkan, Håkon A', 'Koroma, Alimamy P', 'Von Schreeb, Johan']",BMJ Glob Health,,,False
68ad2dd709c43428a872d1d91ff37534082da3f7,PMC,The global pool of simulation exercise materials in health emergency preparedness and response: a scoping review with a health system perspective,http://dx.doi.org/10.1136/bmjgh-2019-001687,PMC6666827,31406594,CC BY-NC,"Simulation Exercises (SimEx) are an established tool in defence and allied security sectors, applied extensively in health security initiatives under national or international legislative requirements, particularly the International Health Regulations (2005). There is, however, a paucity of information on SimEx application to test the functionality of health systems alongside emergency preparedness, response and recovery. Given the important implications health services resilience has for the protection and improvement of human life, this scoping review was undertaken to determine how the publicly available body of existing global SimEx materials considers health systems, together with health security functions in the event of disruptive emergencies. The global review identified 668 articles from literature and 73 products from institutional sources. Relevant screening identified 51 materials suitable to examine from a health system lens using the six health system building blocks as per the WHO Health System Framework. Eight materials were identified for further examination of their ability to test health system functionality from a resilience perspective. SimEx are an effective approach used extensively within health security and emergency response sectors but is not yet adequately used to test health system resilience. Currently available SimEx materials lack an integrated health system perspective and have a limited focus on the quality of services delivered within the context of response to a public health emergency. The materials do not focus on the ability of systems to effectively maintain core services during response. Without adjustment of the scope and focus, currently available SimEx materials do not have the capacity to test health systems to support the development of resilient health systems. Dedicated SimEx materials are urgently needed to fill this gap and harness their potential as an operational tool to contribute to improvements in health systems. They can act as effective global goods to allow testing of different functional aspects of health systems and service delivery alongside emergency preparedness and response. The work was conducted within the scope of the Tackling Deadly Diseases in Africa Programme, funded by the UK Department for International Development, which seeks to strengthen collaboration between the health system and health security clusters to promote health security and build resilient health systems.",2019 Jul 29,"['McDarby, Geraldine', 'Reynolds, Lindy', 'Zibwowa, Zandile', 'Syed, Shams', 'Kelley, Ed', 'Saikat, Sohel']",BMJ Glob Health,,,True
dc11b756bc75339e192c5ed4410a062120c1ad57,PMC,The global pool of simulation exercise materials in health emergency preparedness and response: a scoping review with a health system perspective,http://dx.doi.org/10.1136/bmjgh-2019-001687,PMC6666827,31406594,CC BY-NC,"Simulation Exercises (SimEx) are an established tool in defence and allied security sectors, applied extensively in health security initiatives under national or international legislative requirements, particularly the International Health Regulations (2005). There is, however, a paucity of information on SimEx application to test the functionality of health systems alongside emergency preparedness, response and recovery. Given the important implications health services resilience has for the protection and improvement of human life, this scoping review was undertaken to determine how the publicly available body of existing global SimEx materials considers health systems, together with health security functions in the event of disruptive emergencies. The global review identified 668 articles from literature and 73 products from institutional sources. Relevant screening identified 51 materials suitable to examine from a health system lens using the six health system building blocks as per the WHO Health System Framework. Eight materials were identified for further examination of their ability to test health system functionality from a resilience perspective. SimEx are an effective approach used extensively within health security and emergency response sectors but is not yet adequately used to test health system resilience. Currently available SimEx materials lack an integrated health system perspective and have a limited focus on the quality of services delivered within the context of response to a public health emergency. The materials do not focus on the ability of systems to effectively maintain core services during response. Without adjustment of the scope and focus, currently available SimEx materials do not have the capacity to test health systems to support the development of resilient health systems. Dedicated SimEx materials are urgently needed to fill this gap and harness their potential as an operational tool to contribute to improvements in health systems. They can act as effective global goods to allow testing of different functional aspects of health systems and service delivery alongside emergency preparedness and response. The work was conducted within the scope of the Tackling Deadly Diseases in Africa Programme, funded by the UK Department for International Development, which seeks to strengthen collaboration between the health system and health security clusters to promote health security and build resilient health systems.",2019 Jul 29,"['McDarby, Geraldine', 'Reynolds, Lindy', 'Zibwowa, Zandile', 'Syed, Shams', 'Kelley, Ed', 'Saikat, Sohel']",BMJ Glob Health,,,False
a7eb563733dde1b81b2bd1953087e34925f966c6,PMC,rVSVΔG-ZEBOV-GP (also designated V920) recombinant vesicular stomatitis virus pseudotyped with Ebola Zaire Glycoprotein: Standardized template with key considerations for a risk/benefit assessment,http://dx.doi.org/10.1016/j.jvacx.2019.100009,PMC6668225,31384731,CC BY-NC-ND,"The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety and characteristics of live, recombinant viral vector vaccines. A recent publication by the V3SWG described live, attenuated, recombinant vesicular stomatitis virus (rVSV) as a chimeric virus vaccine for HIV-1 (Clarke et al., 2016). The rVSV vector system is being explored as a platform for development of multiple vaccines. This paper reviews the molecular and biological features of the rVSV vector system, followed by a template with details on the safety and characteristics of a rVSV vaccine against Zaire ebolavirus (ZEBOV). The rVSV-ZEBOV vaccine is a live, replication competent vector in which the VSV glycoprotein (G) gene is replaced with the glycoprotein (GP) gene of ZEBOV. Multiple copies of GP are expressed and assembled into the viral envelope responsible for inducing protective immunity. The vaccine (designated V920) was originally constructed by the National Microbiology Laboratory, Public Health Agency of Canada, further developed by NewLink Genetics Corp. and Merck & Co., and is now in final stages of registration by Merck. The vaccine is attenuated by deletion of the principal virulence factor of VSV (the G protein), which also removes the primary target for anti-vector immunity. The V920 vaccine caused no toxicities after intramuscular (IM) or intracranial injection of nonhuman primates and no reproductive or developmental toxicity in a rat model. In multiple studies, cynomolgus macaques immunized IM with a wide range of virus doses rapidly developed ZEBOV-specific antibodies measured in IgG ELISA and neutralization assays and were fully protected against lethal challenge with ZEBOV virus. Over 20,000 people have received the vaccine in clinical trials; the vaccine has proven to be safe and well tolerated. During the first few days after vaccination, many vaccinees experience a mild acute-phase reaction with fever, headache, myalgia, and arthralgia of short duration; this period is associated with a low-level viremia, activation of anti-viral genes, and increased levels of chemokines and cytokines. Oligoarthritis and rash appearing in the second week occur at a low incidence, and are typically mild-moderate in severity and self-limited. V920 vaccine was used in a Phase III efficacy trial during the West African Ebola epidemic in 2015, showing 100% protection against Ebola Virus Disease, and it has subsequently been deployed for emergency control of Ebola outbreaks in central Africa. The template provided here provides a comprehensive picture of the first rVSV vector to reach the final stage of development and to provide a solution to control of an alarming human disease.",2019 Jan 29,"['Monath, Thomas P.', 'Fast, Patricia E.', 'Modjarrad, Kayvon', 'Clarke, David K.', 'Martin, Brian K.', 'Fusco, Joan', 'Nichols, Richard', 'Heppner, D. Gray', 'Simon, Jakub K.', 'Dubey, Sheri', 'Troth, Sean P.', 'Wolf, Jayanthi', 'Singh, Vidisha', 'Coller, Beth-Ann', 'Robertson, James S.', None]",Vaccine X,,,False
93d77f602ff27ef1575dd6f700d3f39033bba576,PMC,Generation and protective efficacy of a cold-adapted attenuated genotype 2b porcine epidemic diarrhea virus,http://dx.doi.org/10.4142/jvs.2019.20.e32,PMC6669205,31364317,CC BY-NC,"The recent emergence and re-emergence of porcine epidemic diarrhea virus (PEDV) underscore the urgent need for the development of novel, safe, and effective vaccines against the prevailing strain. In this study, we generated a cold-adapted live attenuated vaccine candidate (Aram-P29-CA) by short-term passage of a virulent PEDV isolate at successively lower temperatures in Vero cells. Whole genome sequencing identified 12 amino acid changes in the cold-adapted strain with no insertions and deletions throughout the genome. Animal inoculation experiments confirmed the attenuated phenotype of Aram-P29-CA virus in the natural host. Pregnant sows were orally administered P29-CA live vaccines two doses at 2-week intervals prior to parturition, and the newborn piglets were challenged with the parental virus. The oral homologous prime-boost vaccination of P29-CA significantly improved the survival rate of the piglets and notably mitigated the severity of diarrhea and PEDV fecal shedding after the challenge. Furthermore, strong antibody responses to PEDV were detected in the sera and colostrum of immunized sows and in the sera of their offspring. These results demonstrated that the cold-adapted attenuated virus can be used as a live vaccine in maternal vaccination strategies to provide durable lactogenic immunity and confer passive protection to litters against PEDV.",2019 Jul 9,"['Won, Hokeun', 'Lee, Dong-Uk', 'Jang, Guehwan', 'Noh, Yun-Hee', 'Lee, Seung-Chul', 'Choi, Hwan-Won', 'Yoon, In-Joong', 'Yoo, Han Sang', 'Lee, Changhee']",J Vet Sci,,,True
aeb4261d73ec7020a2ddcd4fdd3778d28cc83434,PMC,Haemophilus parainfluenzae endocarditis with multiple cerebral emboli in a pregnant woman with coronavirus,http://dx.doi.org/10.1016/j.idcr.2019.e00593,PMC6676006,31388489,CC BY-NC-ND,,2019 Jul 10,"['De Castro, Alicia', 'Abu-Hishmeh, Mohammad', 'El Husseini, Ibrahim', 'Paul, Lisa']",IDCases,,,False
94af6bf9cae266730bbc0480ab71595c12072891,PMC,Global Warming and Its Health Impact,http://dx.doi.org/10.15171/ijoem.2017.963,PMC6679631,28051192,CC BY-NC-SA,"Since the mid-19(th) century, human activities have increased greenhouse gases such as carbon dioxide, methane, and nitrous oxide in the Earth's atmosphere that resulted in increased average temperature. The effects of rising temperature include soil degradation, loss of productivity of agricultural land, desertification, loss of biodiversity, degradation of ecosystems, reduced fresh-water resources, acidification of the oceans, and the disruption and depletion of stratospheric ozone. All these have an impact on human health, causing non-communicable diseases such as injuries during natural disasters, malnutrition during famine, and increased mortality during heat waves due to complications in chronically ill patients. Direct exposure to natural disasters has also an impact on mental health and, although too complex to be quantified, a link has even been established between climate and civil violence. Over time, climate change can reduce agricultural resources through reduced availability of water, alterations and shrinking arable land, increased pollution, accumulation of toxic substances in the food chain, and creation of habitats suitable to the transmission of human and animal pathogens. People living in low-income countries are particularly vulnerable. Climate change scenarios include a change in distribution of infectious diseases with warming and changes in outbreaks associated with weather extreme events. After floods, increased cases of leptospirosis, campylobacter infections and cryptosporidiosis are reported. Global warming affects water heating, rising the transmission of water-borne pathogens. Pathogens transmitted by vectors are particularly sensitive to climate change because they spend a good part of their life cycle in a cold-blooded host invertebrate whose temperature is similar to the environment. A warmer climate presents more favorable conditions for the survival and the completion of the life cycle of the vector, going as far as to speed it up as in the case of mosquitoes. Diseases transmitted by mosquitoes include some of the most widespread worldwide illnesses such as malaria and viral diseases. Tick-borne diseases have increased in the past years in cold regions, because rising temperatures accelerate the cycle of development, the production of eggs, and the density and distribution of the tick population. The areas of presence of ticks and diseases that they can transmit have increased, both in terms of geographical extension than in altitude. In the next years the engagement of the health sector would be working to develop prevention and adaptation programs in order to reduce the costs and burden of climate change.",2016 Dec 10,"Rossati, Antonella",Int J Occup Environ Med,,,True
b55aa037b62821a2bcf4463f30caba8c8e662e2b,PMC,The prevalence of respiratory pathogens in adults with community-acquired pneumonia in an outpatient cohort,http://dx.doi.org/10.2147/IDR.S213296,PMC6679678,31440068,CC BY-NC,"PURPOSE: Community-acquired pneumonia is a common illness worldwide. In adults, community-acquired bacterial pneumonia has been well studied, but viral pneumonia is less well understood. We designed this study to identify respiratory pathogens, including common pneumonia-causing bacteria, viruses and atypical pneumonia pathogens, using reverse transcription-polymerase chain reaction. PATIENTS AND METHODS: We conducted a retrospective study of outpatients with community-acquired pneumonia at the Fever Clinic of Peking University Third Hospital. We collected sputum or throat swabs from patients diagnosed with community-acquired pneumonia. Multiplex real-time reverse transcription-polymerase chain reaction was performed for 20 pathogens, including 9 viruses, 3 atypical pathogens and 8 bacteria. RESULTS: There were 232 outpatients enrolled in our study, and 153 patients (65.9%) had positive test results, of which 26.7% were viruses, 19.4% were atypical pathogens and 19.8% were bacteria. Mycoplasma pneumoniae infection was detected at the highest frequency (19.0%), exceeding Streptococcus pneumoniae infection. The most commonly identified viral pathogens were IFVs (15.1%), PIVs (3.4%) and RhV (2.6%). The most commonly identified bacteria were Streptococcus pneumoniae (9.1%), Haemophilus influenza (6.5%) and Klebsiella pneumoniae (2.6%). CONCLUSION: Our study suggests that viruses were commonly detected in outpatients with CAP, and IFVs were the most common viruses, especially during flu season. Patients with viral infection were prone to viral-bacterial coinfection. Mycoplasma pneumoniae was the leading pathogen in the outpatients with CAP. Viral infection occurs in a large number of outpatients with CAP, and it should receive greater attention in clinical work.",2019 Jul 30,"['Chen, Jing', 'Li, Xiaoguang', 'Wang, Wei', 'Jia, Ying', 'Lin, Fei', 'Xu, Jie']",Infect Drug Resist,,,True
94f679e7bf40010e41952e26e8953a5703be64c0,PMC,Furin‐mediated protein processing in infectious diseases and cancer,http://dx.doi.org/10.1002/cti2.1073,PMC6682551,31406574,CC BY-NC,"Proteolytic cleavage regulates numerous processes in health and disease. One key player is the ubiquitously expressed serine protease furin, which cleaves a plethora of proteins at polybasic recognition motifs. Mammalian substrates of furin include cytokines, hormones, growth factors and receptors. Thus, it is not surprising that aberrant furin activity is associated with a variety of disorders including cancer. Furthermore, the enzymatic activity of furin is exploited by numerous viral and bacterial pathogens, thereby enhancing their virulence and spread. In this review, we describe the physiological and pathophysiological substrates of furin and discuss how dysregulation of a simple proteolytic cleavage event may promote infectious diseases and cancer. One major focus is the role of furin in viral glycoprotein maturation and pathogenicity. We also outline cellular mechanisms regulating the expression and activation of furin and summarise current approaches that target this protease for therapeutic intervention.",2019 Aug 5,"['Braun, Elisabeth', 'Sauter, Daniel']",Clin Transl Immunology,,,True
254270af7f396d35475aee946cc1b3f9a3694e29,PMC,IL-27 promotes the expansion of self-renewing CD8(+) T cells in persistent viral infection,http://dx.doi.org/10.1084/jem.20190173,PMC6683984,31164392,CC BY-NC-SA,"Chronic infection and cancer are associated with suppressed T cell responses in the presence of cognate antigen. Recent work identified memory-like CXCR5(+) TCF1(+) CD8(+) T cells that sustain T cell responses during persistent infection and proliferate upon anti-PD1 treatment. Approaches to expand these cells are sought. We show that blockade of interferon type 1 (IFN-I) receptor leads to CXCR5(+) CD8(+) T cell expansion in an IL-27– and STAT1-dependent manner. IFNAR1 blockade promoted accelerated cell division and retention of TCF1 in virus-specific CD8(+) T cells. We found that CD8(+) T cell–intrinsic IL-27 signaling safeguards the ability of TCF1(hi) cells to maintain proliferation and avoid terminal differentiation or programmed cell death. Mechanistically, IL-27 endowed rapidly dividing cells with IRF1, a transcription factor that was required for sustained division in a cell-intrinsic manner. These findings reveal that IL-27 opposes IFN-I to uncouple effector differentiation from cell division and suggest that IL-27 signaling could be exploited to augment self-renewing T cells in chronic infections and cancer.",2019 Aug 5,"['Huang, Zhe', 'Zak, Jaroslav', 'Pratumchai, Isaraphorn', 'Shaabani, Namir', 'Vartabedian, Vincent F.', 'Nguyen, Nhan', 'Wu, Tuoqi', 'Xiao, Changchun', 'Teijaro, John R.']",J Exp Med,,,True
97ba00ce6a99f88a1c51898bdd85221df6b74e50,PMC,IL-27 promotes the expansion of self-renewing CD8(+) T cells in persistent viral infection,http://dx.doi.org/10.1084/jem.20190173,PMC6683984,31164392,CC BY-NC-SA,"Chronic infection and cancer are associated with suppressed T cell responses in the presence of cognate antigen. Recent work identified memory-like CXCR5(+) TCF1(+) CD8(+) T cells that sustain T cell responses during persistent infection and proliferate upon anti-PD1 treatment. Approaches to expand these cells are sought. We show that blockade of interferon type 1 (IFN-I) receptor leads to CXCR5(+) CD8(+) T cell expansion in an IL-27– and STAT1-dependent manner. IFNAR1 blockade promoted accelerated cell division and retention of TCF1 in virus-specific CD8(+) T cells. We found that CD8(+) T cell–intrinsic IL-27 signaling safeguards the ability of TCF1(hi) cells to maintain proliferation and avoid terminal differentiation or programmed cell death. Mechanistically, IL-27 endowed rapidly dividing cells with IRF1, a transcription factor that was required for sustained division in a cell-intrinsic manner. These findings reveal that IL-27 opposes IFN-I to uncouple effector differentiation from cell division and suggest that IL-27 signaling could be exploited to augment self-renewing T cells in chronic infections and cancer.",2019 Aug 5,"['Huang, Zhe', 'Zak, Jaroslav', 'Pratumchai, Isaraphorn', 'Shaabani, Namir', 'Vartabedian, Vincent F.', 'Nguyen, Nhan', 'Wu, Tuoqi', 'Xiao, Changchun', 'Teijaro, John R.']",J Exp Med,,,False
f41bb45e2257663c953fd7d3ff1c78f9b37ba268,PMC,A Systematic Review of Social Contact Surveys to Inform Transmission Models of Close-contact Infections,http://dx.doi.org/10.1097/EDE.0000000000001047,PMC6684224,31274572,CC BY-NC-ND,"BACKGROUND: Researchers increasingly use social contact data to inform models for infectious disease spread with the aim of guiding effective policies about disease prevention and control. In this article, we undertake a systematic review of the study design, statistical analyses, and outcomes of the many social contact surveys that have been published. METHODS: We systematically searched PubMed and Web of Science for articles regarding social contact surveys. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines as closely as possible. RESULTS: In total, we identified 64 social contact surveys, with more than 80% of the surveys conducted in high-income countries. Study settings included general population (58%), schools or universities (37%), and health care/conference/research institutes (5%). The largest number of studies did not focus on a specific age group (38%), whereas others focused on adults (32%) or children (19%). Retrospective (45%) and prospective (41%) designs were used most often with 6% using both for comparison purposes. The definition of a contact varied among surveys, e.g., a nonphysical contact may require conversation, close proximity, or both. We identified age, time schedule (e.g., weekday/weekend), and household size as relevant determinants of contact patterns across a large number of studies. CONCLUSIONS: We found that the overall features of the contact patterns were remarkably robust across several countries, and irrespective of the study details. By considering the most common approach in each aspect of design (e.g., sampling schemes, data collection, definition of contact), we could identify recommendations for future contact data surveys that may be used to facilitate comparison between studies.",2019 Sep 30,"['Hoang, Thang', 'Coletti, Pietro', 'Melegaro, Alessia', 'Wallinga, Jacco', 'Grijalva, Carlos G.', 'Edmunds, John W.', 'Beutels, Philippe', 'Hens, Niel']",Epidemiology,,,True
bd614a6233ff72830a79371d92a7680e1b8af33b,PMC,A Systematic Review of Social Contact Surveys to Inform Transmission Models of Close-contact Infections,http://dx.doi.org/10.1097/EDE.0000000000001047,PMC6684224,31274572,CC BY-NC-ND,"BACKGROUND: Researchers increasingly use social contact data to inform models for infectious disease spread with the aim of guiding effective policies about disease prevention and control. In this article, we undertake a systematic review of the study design, statistical analyses, and outcomes of the many social contact surveys that have been published. METHODS: We systematically searched PubMed and Web of Science for articles regarding social contact surveys. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines as closely as possible. RESULTS: In total, we identified 64 social contact surveys, with more than 80% of the surveys conducted in high-income countries. Study settings included general population (58%), schools or universities (37%), and health care/conference/research institutes (5%). The largest number of studies did not focus on a specific age group (38%), whereas others focused on adults (32%) or children (19%). Retrospective (45%) and prospective (41%) designs were used most often with 6% using both for comparison purposes. The definition of a contact varied among surveys, e.g., a nonphysical contact may require conversation, close proximity, or both. We identified age, time schedule (e.g., weekday/weekend), and household size as relevant determinants of contact patterns across a large number of studies. CONCLUSIONS: We found that the overall features of the contact patterns were remarkably robust across several countries, and irrespective of the study details. By considering the most common approach in each aspect of design (e.g., sampling schemes, data collection, definition of contact), we could identify recommendations for future contact data surveys that may be used to facilitate comparison between studies.",2019 Sep 30,"['Hoang, Thang', 'Coletti, Pietro', 'Melegaro, Alessia', 'Wallinga, Jacco', 'Grijalva, Carlos G.', 'Edmunds, John W.', 'Beutels, Philippe', 'Hens, Niel']",Epidemiology,,,True
55f664e8e3b18388964ec14c61a7b655b786ef31,PMC,Is Fever a Red Flag for Bacterial Pneumonia in Children With Viral Bronchiolitis?,http://dx.doi.org/10.1177/2333794X19868660,PMC6686317,31431903,CC BY-NC,"We hypothesized that fever in children with viral bronchiolitis indicates the need for consideration of superimposed bacterial pneumonia. We conducted a retrospective study of 349 children aged 2 years and younger with diagnoses of respiratory syncytial virus (RSV) and viral upper respiratory infection. Data were analyzed using Pearson χ(2) test. One hundred seventy-eight children had RSV with no other identified virus. The majority of children (56%) who had only RSV were afebrile. Febrile children with RSV were over twice as likely to be diagnosed with bacterial pneumonia as those who were afebrile (60% vs 27%, P < .001). In the 171 children who had bronchiolitis caused by a virus other than RSV, 51% were afebrile. These children were 8 times more likely to be diagnosed with pneumonia than those who were afebrile (65% vs 8%, P < .001). Evaluation of febrile children with viral bronchiolitis may allow early diagnosis and treatment of secondary bacterial pneumonia.",2019 Aug 6,"['Elmore, Dominique', 'Yaslam, Balfaqih', 'Putty, Krista', 'Magrane, Thomas', 'Abadir, Anthony', 'Bhatt, Saloni', 'Frazier, Marie', 'Flesher, Susan']",Glob Pediatr Health,,,True
3b8b2a835cfa770c6cef711d52e1f1e869d8aca8,PMC,Tumor-Treating Fields Induce RAW264.7 Macrophage Activation Via NK-κB/MAPK Signaling Pathways,http://dx.doi.org/10.1177/1533033819868225,PMC6691660,31401938,CC BY-NC,"OBJECTIVE: Tumor-treating fields are currently used to successfully treat various cancers; however, the specific pathways associated with its efficacy remain unknown in the immune responses. Here, we evaluated tumor-treating fields–mediated initiation of the macrophage-specific immune response. MATERIALS AND METHODS: We subjected RAW 264.7 mouse macrophages to clinically relevant levels of tumor-treating fields (0.9 V/cm, 150 kHz) and evaluated alterations in cytokine expression and release, as well as cell viability. Additionally, we investigated the status of immunomodulatory pathways to determine their roles in tumor-treating fields–mediated immune activation. RESULTS AND DISCUSSION: Our results indicated that tumor-treating fields treatment at 0.9 V/cm decreased cell viability and increased cytokine messenger RNA/protein levels, as well as levels of nitric oxide and reactive oxygen species, relative to controls. The levels of tumor necrosis factor α, interleukin 1β, and interleukin 6 were markedly increased in tumor-treating fields–treated RAW 264.7 cells cocultured with 4T1 murine mammary carcinoma cells compared with those in 4T1 or RAW 264.7 cells with or without tumor-treating fields treatment. Moreover, the viability of 4T1 cells treated with the conditioned medium of tumor-treating fields–stimulated RAW 264.7 cells decreased, indicating that macrophage activation by tumor-treating fields effectively killed the tumor cells. Moreover, tumor-treating fields treatment activated the nuclear factor κB and mitogen-activated protein kinase pathways involved in immunomodulatory signaling. CONCLUSION: These results provide critical insights into the mechanisms through which tumor-treating fields affect macrophage-specific immune responses and the efficacy of this method for cancer treatment.",2019 Aug 11,"['Park, Jeong-In', 'Song, Kyung-Hee', 'Jung, Seung-Youn', 'Ahn, Jiyeon', 'Hwang, Sang-Gu', 'Kim, Joon', 'Kim, Eun Ho', 'Song, Jie-Young']",Technol Cancer Res Treat,,,True
ebe2d78994fb611b59146b5480d460b153b0af82,PMC,Antimicrobial activity of novel synthesized coumarin based transitional metal complexes,http://dx.doi.org/10.1016/j.jtumed.2016.10.004,PMC6694993,31435225,CC BY-NC-ND,OBJECTIVES: To synthesize new transitional metal complexes derived from 3-aryl-azo-4-hydroxy coumarin analogues and to evaluate their antimicrobial activities. METHODS: The syntheses of complexes of coumarin analogues were accomplished by mixing a hydro-alcoholic solution of 3-aryl-azo-4-hydroxy coumarin analogues with transition metal chlorides. The structural environment of the synthesized molecules was characterized using different instrumental methods. The antimicrobial activity of the compounds was determined by the agar well diffusion method. RESULTS: The cobalt complexes of (E)-3-((4-chlorophenyl) diazenyl)-4-hydroxy-2H-chromen-2-one (HL(1)): (4a) and (E)-3-((4-methoxyphenyl) diazenyl)-4-hydroxy-2H-chromen-2-one (HL(2)): (4e) showed excellent antimicrobial activities compared with their ligands. CONCLUSION: The reports of the antimicrobial investigation showed that the cobalt complexes of 3-aryl-azo-4-hydroxy coumarin analogues exhibited potential antimicrobial activity that was stronger than that of their ligands.,2016 Nov 24,"['Sahoo, Jyotirmaya', 'Paidesetty, Sudhir K.']",J Taibah Univ Med Sci,,,False
cda2b34b3bd99847fe20196abee563da22b81207,PMC,Antimicrobial activity of novel synthesized coumarin based transitional metal complexes,http://dx.doi.org/10.1016/j.jtumed.2016.10.004,PMC6694993,31435225,CC BY-NC-ND,OBJECTIVES: To synthesize new transitional metal complexes derived from 3-aryl-azo-4-hydroxy coumarin analogues and to evaluate their antimicrobial activities. METHODS: The syntheses of complexes of coumarin analogues were accomplished by mixing a hydro-alcoholic solution of 3-aryl-azo-4-hydroxy coumarin analogues with transition metal chlorides. The structural environment of the synthesized molecules was characterized using different instrumental methods. The antimicrobial activity of the compounds was determined by the agar well diffusion method. RESULTS: The cobalt complexes of (E)-3-((4-chlorophenyl) diazenyl)-4-hydroxy-2H-chromen-2-one (HL(1)): (4a) and (E)-3-((4-methoxyphenyl) diazenyl)-4-hydroxy-2H-chromen-2-one (HL(2)): (4e) showed excellent antimicrobial activities compared with their ligands. CONCLUSION: The reports of the antimicrobial investigation showed that the cobalt complexes of 3-aryl-azo-4-hydroxy coumarin analogues exhibited potential antimicrobial activity that was stronger than that of their ligands.,2016 Nov 24,"['Sahoo, Jyotirmaya', 'Paidesetty, Sudhir K.']",J Taibah Univ Med Sci,,,False
eaf89905f4e044366327ca15b97b47a03c79883a,PMC,Case report: Detection of the Middle East respiratory syndrome corona virus (MERS-CoV) in nasal secretions of a dead human,http://dx.doi.org/10.1016/j.jtumed.2017.07.004,PMC6695009,31435338,CC BY-NC-ND,"The Middle East respiratory syndrome coronavirus (MERS-CoV) has been recognized as a highly pathogenic virus that infects the human respiratory tract and has high morbidity and mortality. The MERS-CoV is a huge burden on Saudi Arabian health-care facilities, causing approximately 40% mortality. The transmission mechanism of the virus is still not well understood. Therefore, the prevention of any route of transmission is the best measure to arrest the spread of this disease. Using the real time polymerase chain reaction (RT-PCR), MERS-CoV was detected in the nasal secretions of a human cadaver. Full precautions should be applied and carefully followed to prevent the transmission of the virus, especially among health care workers.",2017 Aug 16,"Mahallawi, Waleed H.",J Taibah Univ Med Sci,,,False
95b9bac4d7a86402203e36f44eb826352f406b13,PMC,Diagnosis and management of a case of retroperitoneal eosinophilic sclerosing fibroplasia in a cat,http://dx.doi.org/10.1177/2055116919867178,PMC6699013,31452913,CC BY-NC,"CASE SUMMARY: A 4-year-old neutered male cat was presented with a 2-month history of intermittent constipation that progressed to obstipation. Primary clinical findings included a large, multi lobulated mass in the caudodorsal abdomen, peripheral eosinophilia and hyperglobulinemia. Abdominal imaging revealed a multilobulated, cavitated mass in the sublumbar region. Exploratory celiotomy revealed multiple firm masses in the sublumbar retroperitoneal space causing ventral displacement and compression of the descending colon with extension of the masses into the pelvic canal. Histopathology was consistent with feline gastrointestinal eosinophilic sclerosing fibroplasia (FGESF). Aerobic culture was positive for Staphylococcus aureus. The cat was treated with prednisolone (2 mg/kg PO q24h), lactulose (0.5 g/kg PO q8h), amoxicillin/clavulanic acid (62.5 mg/cat PO q12h for 1 month) and fenbendazole (50 mg/kg PO q24h for 5 days). Six months postoperatively, the cat had no recurrence of clinical signs. Repeat evaluation and imaging at day 732 postoperatively revealed marked improvement of the abdominal mass, resolution of peripheral eosinophilia and no clinical signs with continued prednisolone therapy (0.5 mg/kg PO q24h). RELEVANCE AND NOVEL INFORMATION: This is a report of a primary extramural FGESF lesion, and the first description of characteristics of FGESF on CT. Previous evidence suggests that the most favorable outcomes require immunosuppressive therapy and complete surgical excision; however, this case demonstrates a favorable outcome with medical management alone.",2019 Aug 16,"['Thieme, Maureen E', 'Olsen, Anastasia M', 'Woolcock, Andrew D', 'Miller, Margaret A', 'Simons, Micha C']",JFMS Open Rep,,,True
567a4ae944e5286ed25f8ab20dc098ed570b74d8,PMC,Fluoroscopy-guided balloon dilation of a proximal urethral stricture caused by a urethral membrane in a female cat,http://dx.doi.org/10.1177/2055116919867177,PMC6699014,31452912,CC BY-NC,"CASE SUMMARY: A proximal urethral stricture was diagnosed by retrograde urethrogram in a 2-year-old female neutered cat, which was referred following a 2-month history of stranguria, pollakiuria and urinary incontinence. Cystoscopic examination confirmed the presence of a severe narrowing of the proximal urethra near to the bladder neck, consisting of a membrane arising from the urethral mucosa. Fluoroscopy-guided balloon dilation was performed. Twelve months after the procedure, the cat did not show any recurrence of clinical signs. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first report of a proximal urethral stricture in a cat. Management by fluoroscopy-guided balloon dilation proved to be a successful and minimally invasive option with an excellent outcome.",2019 Aug 16,"['Rincon Alvarez, Javier', 'Smith, Victoria', 'Broome, Cameron']",JFMS Open Rep,,,True
7a920d6b53c292f53323cb6c5109732a9575e33c,PMC,Epitope-based vaccine as a universal vaccination strategy against Toxoplasma gondii infection: A mini-review,http://dx.doi.org/10.5455/javar.2019.f329,PMC6702889,31453188,CC BY-NC,"Despite the significant progress in the recent efforts toward developing an effective vaccine against toxoplasmosis, the search for new protective vaccination strategy still remains a challenge and elusive goal because it becomes the appropriate way to prevent the disease. Various experimental approaches in the past few years showed that developing a potential vaccine against the disease can be achievable. The combination of multi-epitopes expressing different stages of the parasite life cycle has become an optimal strategy for acquiring a potent, safe, and effective vaccine. Epitope-based vaccines have gained attention as alternative vaccine candidates due to their ability of inducing protective immune responses. This mini-review highlights the current status and the prospects of Toxoplasma gondii vaccine development along with the application of epitope-based vaccine in the future parasite immunization as a novel under development and evaluation strategy.",2019 Mar 24,"['Hajissa, Khalid', 'Zakaria, Robaiza', 'Suppian, Rapeah', 'Mohamed, Zeehaida']",J Adv Vet Anim Res,,,True
860ffcab2771f1935ac5a59e986d416a603b3de3,PMC,Diversity and prevalence of parasitic infestation with zoonotic potential in dromedary camel (Camelus dromedarius) and fat-tailed sheep (dhumba) in Bangladesh,http://dx.doi.org/10.5455/javar.2019.f324,PMC6702934,31453183,CC BY-NC,"OBJECTIVE: Parasitic infestation is a major cause of losses in livestock production in tropical regions. A cross-sectional study was conducted to determine the prevalence of Gastro-intestinal (GI) parasites of dromedary camel (Camelus dromedarius) and fat-tailed sheep (dhumba), and the prevalence of hemoparasites in camel from Dhaka, Bangladesh. MATERIALS AND METHODS: A total of 87 fecal samples (32 dhumba and 55 camel) and 55 camel blood samples were collected during September–October 2015. Fecal samples were examined by direct smear, sedimentation method, flotation technique, and McMaster technique for GI parasite. Giemsa stained blood smears were examined under microscope for hemoparasite detection. RESULTS: 62% camel (n = 34; 95% confidence interval (CI): 47.7–74.6) were infected with at least one genus of parasite. 15% camel were harboring more than one genus of parasite. The prevalence of GI parasite and hemoparasite in camel were recorded as Trichuris spp. (n = 16; 29%; 95% CI: 17.6–42.9), Balantidium coli (n = 12; 22%; 95% CI: 11.8–35.0), Trichostrongylus spp. (n = 7; 13%; 95% CI: 5.3–24.5), Strongyloides spp. (n = 5; 9%; 95% CI: 3.0–20.0), Anaplasma spp. (n = 5; 9%; 95% CI: 3.02–20.0), Paragonimus spp. (n = 1; 2%; 95% CI: 0.05–9.7), Schistosoma spp. (n = 1; 2%; 95% CI: 0.05–9.7), Hymenolepis spp. (n = 1; 2%; 95% CI: 0.05–9.7), Moniezia spp. (n = 1; 2%; 95% CI: 0.05–9.7), and Babesia spp. (n = 1; 2%; 95% CI: 0.05–9.7). Mean EPG feces of camel was 291.76 ± 42.03 with a range of 0–1,400. Total 59.4% dhumba (n = 19; 95% CI: 41–76) were positive for GI parasite, including Trichostrongylus spp. (n = 10; 31.3%; 95% CI: 16.1–50), Strongyloides spp. (n = 9; 28%; 95% CI: 13.8–46.8), B. coli (n = 5; 15.6%; 95% CI: 5.3–32.8), and Trichuris spp. (n = 4; 12.5%; 95% CI: 3.5–28.9). CONCLUSIONS: High percentage of parasitic infestation in camel and dhumba in the present study refers to the necessity of use of anthelmintic for health and production improvement and to prevent zoonotic parasite transmission to animal handler and workers.",2019 Feb 25,"['Islam, Ariful', 'Islam, Shariful', 'Ferdous, Jinnat', 'Rahman, Md Kaisar', 'Uddin, Md Helal', 'Akter, Sazeda', 'Rahman, Md Hafizar', 'Hassan, Mohammad Mahmudul']",J Adv Vet Anim Res,,,True
9791d7ab94765e2012facc4084c479cedbdfaf5e,PMC,Organisation of primary health care in the Asia-Pacific region: developing a prioritised research agenda,http://dx.doi.org/10.1136/bmjgh-2019-001467,PMC6703300,31478022,CC BY-NC,"Health system planners in low- and middle-income countries (LMIC) of the Asia-Pacific region seeking to reorient primary health care (PHC) systems to achieve universal health coverage may be hindered by lack of knowledge of what works in their setting. With limited resources for research available, it is important to identify evidence-based strategies for reorganising PHC delivery, determine where relevant evidence gaps exist and prioritise these for future study. This paper describes an approach for doing this using the best available evidence combined with consultation to establish evidence priorities. We first reviewed PHC organisational interventions in Asia-Pacific LMICs and ascertained evidence gaps. The largest gaps related to interventions to promote access to essential medicines, patient management tools, effective health promotion strategies and service planning and accountability. Evidence from Pacific Island countries was particularly scant. We then engaged an expert panel of 22 PHC stakeholders from seven Asia-Pacific LMICs in a Delphi exercise to identify priority questions for future research. Research priorities were: (1) identifying effective PHC service delivery models for chronic diseases; (2) devising sustainable models of disease integration; (3) optimising task shifting; (4) understanding barriers to care continuity; (5) projecting future PHC needs; and (6) designing appropriate PHC service packages. Notably, stakeholder-determined priorities reflected large, context-dependent system issues, while evidence gaps centred on discrete interventions. Future research on the organisation of PHC services in Asia-Pacific LMICs should incorporate codesign principles to engage researchers and national PHC system stakeholders, and innovative methods that build on existing evidence and account for system complexity.",2019 Aug 16,"['Palagyi, Anna', 'Dodd, Rebecca', 'Jan, Stephen', 'Nambiar, Devaki', 'Joshi, Rohina', 'Tian, Maoyi', 'Abimbola, Seye', 'Peiris, David']",BMJ Glob Health,,,True
70a52d0582ae02f1290e8263ad02b7f602a88a3b,PMC,Organisation of primary health care in the Asia-Pacific region: developing a prioritised research agenda,http://dx.doi.org/10.1136/bmjgh-2019-001467,PMC6703300,31478022,CC BY-NC,"Health system planners in low- and middle-income countries (LMIC) of the Asia-Pacific region seeking to reorient primary health care (PHC) systems to achieve universal health coverage may be hindered by lack of knowledge of what works in their setting. With limited resources for research available, it is important to identify evidence-based strategies for reorganising PHC delivery, determine where relevant evidence gaps exist and prioritise these for future study. This paper describes an approach for doing this using the best available evidence combined with consultation to establish evidence priorities. We first reviewed PHC organisational interventions in Asia-Pacific LMICs and ascertained evidence gaps. The largest gaps related to interventions to promote access to essential medicines, patient management tools, effective health promotion strategies and service planning and accountability. Evidence from Pacific Island countries was particularly scant. We then engaged an expert panel of 22 PHC stakeholders from seven Asia-Pacific LMICs in a Delphi exercise to identify priority questions for future research. Research priorities were: (1) identifying effective PHC service delivery models for chronic diseases; (2) devising sustainable models of disease integration; (3) optimising task shifting; (4) understanding barriers to care continuity; (5) projecting future PHC needs; and (6) designing appropriate PHC service packages. Notably, stakeholder-determined priorities reflected large, context-dependent system issues, while evidence gaps centred on discrete interventions. Future research on the organisation of PHC services in Asia-Pacific LMICs should incorporate codesign principles to engage researchers and national PHC system stakeholders, and innovative methods that build on existing evidence and account for system complexity.",2019 Aug 16,"['Palagyi, Anna', 'Dodd, Rebecca', 'Jan, Stephen', 'Nambiar, Devaki', 'Joshi, Rohina', 'Tian, Maoyi', 'Abimbola, Seye', 'Peiris, David']",BMJ Glob Health,,,False
0b773ab6729646ecd09b85cb16354cb78a528865,PMC,Organisation of primary health care in the Asia-Pacific region: developing a prioritised research agenda,http://dx.doi.org/10.1136/bmjgh-2019-001467,PMC6703300,31478022,CC BY-NC,"Health system planners in low- and middle-income countries (LMIC) of the Asia-Pacific region seeking to reorient primary health care (PHC) systems to achieve universal health coverage may be hindered by lack of knowledge of what works in their setting. With limited resources for research available, it is important to identify evidence-based strategies for reorganising PHC delivery, determine where relevant evidence gaps exist and prioritise these for future study. This paper describes an approach for doing this using the best available evidence combined with consultation to establish evidence priorities. We first reviewed PHC organisational interventions in Asia-Pacific LMICs and ascertained evidence gaps. The largest gaps related to interventions to promote access to essential medicines, patient management tools, effective health promotion strategies and service planning and accountability. Evidence from Pacific Island countries was particularly scant. We then engaged an expert panel of 22 PHC stakeholders from seven Asia-Pacific LMICs in a Delphi exercise to identify priority questions for future research. Research priorities were: (1) identifying effective PHC service delivery models for chronic diseases; (2) devising sustainable models of disease integration; (3) optimising task shifting; (4) understanding barriers to care continuity; (5) projecting future PHC needs; and (6) designing appropriate PHC service packages. Notably, stakeholder-determined priorities reflected large, context-dependent system issues, while evidence gaps centred on discrete interventions. Future research on the organisation of PHC services in Asia-Pacific LMICs should incorporate codesign principles to engage researchers and national PHC system stakeholders, and innovative methods that build on existing evidence and account for system complexity.",2019 Aug 16,"['Palagyi, Anna', 'Dodd, Rebecca', 'Jan, Stephen', 'Nambiar, Devaki', 'Joshi, Rohina', 'Tian, Maoyi', 'Abimbola, Seye', 'Peiris, David']",BMJ Glob Health,,,False
0ace222a6c33986dfe57d3f24779fe5f674724c7,PMC,Organisation of primary health care in the Asia-Pacific region: developing a prioritised research agenda,http://dx.doi.org/10.1136/bmjgh-2019-001467,PMC6703300,31478022,CC BY-NC,"Health system planners in low- and middle-income countries (LMIC) of the Asia-Pacific region seeking to reorient primary health care (PHC) systems to achieve universal health coverage may be hindered by lack of knowledge of what works in their setting. With limited resources for research available, it is important to identify evidence-based strategies for reorganising PHC delivery, determine where relevant evidence gaps exist and prioritise these for future study. This paper describes an approach for doing this using the best available evidence combined with consultation to establish evidence priorities. We first reviewed PHC organisational interventions in Asia-Pacific LMICs and ascertained evidence gaps. The largest gaps related to interventions to promote access to essential medicines, patient management tools, effective health promotion strategies and service planning and accountability. Evidence from Pacific Island countries was particularly scant. We then engaged an expert panel of 22 PHC stakeholders from seven Asia-Pacific LMICs in a Delphi exercise to identify priority questions for future research. Research priorities were: (1) identifying effective PHC service delivery models for chronic diseases; (2) devising sustainable models of disease integration; (3) optimising task shifting; (4) understanding barriers to care continuity; (5) projecting future PHC needs; and (6) designing appropriate PHC service packages. Notably, stakeholder-determined priorities reflected large, context-dependent system issues, while evidence gaps centred on discrete interventions. Future research on the organisation of PHC services in Asia-Pacific LMICs should incorporate codesign principles to engage researchers and national PHC system stakeholders, and innovative methods that build on existing evidence and account for system complexity.",2019 Aug 16,"['Palagyi, Anna', 'Dodd, Rebecca', 'Jan, Stephen', 'Nambiar, Devaki', 'Joshi, Rohina', 'Tian, Maoyi', 'Abimbola, Seye', 'Peiris, David']",BMJ Glob Health,,,True
7fcb59f56baadd5c096e583c5620f6904f4275f2,PMC,The molecular epidemiology of respiratory viruses in military trainees in Iran,http://dx.doi.org/10.34171/mjiri.33.40,PMC6708098,31456964,CC BY-NC-SA,"Background: Military populations are more prone to respiratory infections worldwide. There is a dearth of research about the role of viral pathogens in the etiology of respiratory infections in military trainees in Iran. Hence, we aimed to investigate the molecular epidemiology and clinical symptoms of respiratory viruses among this population. Methods: This cross-sectional study was performed on 400 military trainees with symptoms of respiratory infection, referred to the military medical clinic center in the basic military training camp of the General Staff of the Armed Forces of the Islamic Republic of Iran. Nucleic acid extraction from the throat or nasopharyngeal swab samples was performed by an automated extraction system. The extracts were then analyzed by the CLART® PneumoVir array system for the detection of respiratory viruses. Results: All military trainees were male, aged between 18 and 57 years (mean: 21.69 years). Sore throat (75.5%), rhinorrhea (63.2%), cough (59.2%), fever (59.2%), and nasal congestion (50.5%) were amongst the most common symptoms. Overall, viral pathogens were detected in a total count of 124 (31%). The most commonly detected viruses were rhinovirus (7.2%), respiratory syncytial virus A (7.2%) and influenza B virus (6%). Conclusion: This study was an important first step for understanding the etiological role of viral pathogens in respiratory infection among military trainees population in Iran. Our results indicated that rhinovirus, respiratory syncytial virus A and influenza B virus are important viral pathogens causing respiratory infection in military trainees, respectively. However, further multi-center studies with larger sample size are strongly recommended to confirm our findings.",2019 May 8,"['Tavakoli, Ahmad', 'Karbalaie Niya, Mohammad Hadi', 'Bokharaei-Salim, Farah', 'Farahmand, Mohammad', 'Izadi, Morteza', 'Dorostkar, Ruhollah', 'Keyvani, Hossein']",Med J Islam Repub Iran,,,False
97180e8069348d5c8f1db6a79d2dbe4d6a586cf5,PMC,"Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases",http://dx.doi.org/10.2147/IDR.S208576,PMC6709804,31686866,CC BY-NC,"Macrophages are a functionally heterogeneous group of cells with specialized functions depending not only on their subgroup but also on the function of the organ or tissue in which the cells are located. The concept of macrophage phenotypic heterogeneity has been investigated since the 1980s, and more recent studies have identified a diverse spectrum of phenotypic subpopulations. Several types of macrophages play a central role in the response to infectious agents and, along with other components of the immune system, determine the clinical outcome of major infectious diseases. Here, we review the functions of various macrophage phenotypic subpopulations, the concept of macrophage polarization, and the influence of these cells on the evolution of infections. In addition, we emphasize their role in the immune response in vivo and in situ, as well as the molecular effectors and signaling mechanisms used by these cells. Furthermore, we highlight the mechanisms of immune evasion triggered by infectious agents to counter the actions of macrophages and their consequences. Our aim here is to provide an overview of the role of macrophages in the pathogenesis of critical transmissible diseases and discuss how elucidation of this relationship could enhance our understanding of the host–pathogen association in organ-specific immune responses.",2019 Aug 22,"['de Sousa, Jorge Rodrigues', 'Da Costa Vasconcelos, Pedro Fernando', 'Quaresma, Juarez Antonio Simões']",Infect Drug Resist,,,True
00d4ff0cfe5582b3f2746b2a33d67f6bd4307e98,PMC,"ULK1/2 Restricts the Formation of Inducible SINT-Speckles, Membraneless Organelles Controlling the Threshold of TBK1 Activation",http://dx.doi.org/10.1016/j.isci.2019.08.001,PMC6710720,31442668,CC BY-NC-ND,"Membraneless organelles (MLOs) are liquid-like subcellular compartments providing spatiotemporal control to biological processes. This study reveals that cellular stress leads to the incorporation of the adaptor protein SINTBAD (TBKBP1) into membraneless, cytosolic speckles. Determination of the interactome identified >100 proteins forming constitutive and stress-inducible members of an MLO that we termed SINT-speckles. SINT-speckles partially colocalize with activated TBK1, and deletion of SINTBAD and the SINT-speckle component AZI2 leads to impaired TBK1 phosphorylation. Dynamic formation of SINT-speckles is positively controlled by the acetyltransferase KAT2A (GCN5) and antagonized by heat shock protein-mediated chaperone activity. SINT-speckle formation is also inhibited by the autophagy-initiating kinases ULK1/2, and knockdown of these kinases prevented focal TBK1 phosphorylation in a pathway-specific manner. The phlebovirus-encoded non-structural protein S enhances ULK1-mediated TBK1 phosphorylation and shows a stress-induced translocation to SINT-speckles, raising the possibility that viruses can also target this signaling hub to manipulate host cell functions.",2019 Aug 6,"['Saul, Vera Vivian', 'Seibert, Markus', 'Krüger, Marcus', 'Jeratsch, Sylvia', 'Kracht, Michael', 'Schmitz, Michael Lienhard']",iScience,,,False
bccd7fb26272a0c36186a098011b7ca88004a019,PMC,"ULK1/2 Restricts the Formation of Inducible SINT-Speckles, Membraneless Organelles Controlling the Threshold of TBK1 Activation",http://dx.doi.org/10.1016/j.isci.2019.08.001,PMC6710720,31442668,CC BY-NC-ND,"Membraneless organelles (MLOs) are liquid-like subcellular compartments providing spatiotemporal control to biological processes. This study reveals that cellular stress leads to the incorporation of the adaptor protein SINTBAD (TBKBP1) into membraneless, cytosolic speckles. Determination of the interactome identified >100 proteins forming constitutive and stress-inducible members of an MLO that we termed SINT-speckles. SINT-speckles partially colocalize with activated TBK1, and deletion of SINTBAD and the SINT-speckle component AZI2 leads to impaired TBK1 phosphorylation. Dynamic formation of SINT-speckles is positively controlled by the acetyltransferase KAT2A (GCN5) and antagonized by heat shock protein-mediated chaperone activity. SINT-speckle formation is also inhibited by the autophagy-initiating kinases ULK1/2, and knockdown of these kinases prevented focal TBK1 phosphorylation in a pathway-specific manner. The phlebovirus-encoded non-structural protein S enhances ULK1-mediated TBK1 phosphorylation and shows a stress-induced translocation to SINT-speckles, raising the possibility that viruses can also target this signaling hub to manipulate host cell functions.",2019 Aug 6,"['Saul, Vera Vivian', 'Seibert, Markus', 'Krüger, Marcus', 'Jeratsch, Sylvia', 'Kracht, Michael', 'Schmitz, Michael Lienhard']",iScience,,,False
bc0e1d6e96b004296ea87bde20bf39334df6d9b6,PMC,"Improving adherence to lung cancer guidelines: a quality improvement project that uses chart review, audit and feedback approach",http://dx.doi.org/10.1136/bmjoq-2018-000436,PMC6711445,31523724,CC BY-NC,"INTRODUCTION: The implementation of evidence-based clinical practice guidelines is one of the most effective interventions for improving quality of care. A gap between guidelines and clinical practice often exists, which may result in patients not receiving appropriate care. This project aimed at improving adherence to lung cancer guidelines at our institution. METHOD: The records of patients with lung cancer were evaluated for adherence to guidelines by using an auditing tool that was developed to capture pertinent information. The study team collected data about the following variables: compliance with documentation of pathological diagnosis, documentation of disease stage prior to treatment initiation, presentation at thoracic tumour board within 30 days of diagnosis, management course, and management of end of life in terms of early ‘no code’ initiation, stopping chemotherapy and referral to palliative care prior to 2 weeks of death. Annual audits were performed from 2012 to 2015. Education and discussion with team members to address the deviations were the main interventions to improve adherence. RESULTS: The baseline measurements were taken in 2012 (49 patients). Histological subtype identification improved from 94% to 100%. Presentation of new cases at the tumour board improved from 35% to 82%. Testing for epidermal growth factor receptor mutation for non-squamous cell lung cancer improved from 77% to 100%. The staging was documented in 100% of the cases. CONCLUSION: Running audits to monitor adherence to guidelines and discussions with the team have a positive effect on providing consistent evidence-based care for patients with lung cancer.",2019 Aug 26,"['Jazieh, Abdulrahman', 'Alkaiyat, Mohammad Omar', 'Ali, Yosra', 'Hashim, Mohamed Ahmed', 'Abdelhafiz, Nafisa', 'Al Olayan, Ashwaq']",BMJ Open Qual,,,True
6b161d7b35ea02229e8b983f54638dbcc66c9467,PMC,"Improving adherence to lung cancer guidelines: a quality improvement project that uses chart review, audit and feedback approach",http://dx.doi.org/10.1136/bmjoq-2018-000436,PMC6711445,31523724,CC BY-NC,"INTRODUCTION: The implementation of evidence-based clinical practice guidelines is one of the most effective interventions for improving quality of care. A gap between guidelines and clinical practice often exists, which may result in patients not receiving appropriate care. This project aimed at improving adherence to lung cancer guidelines at our institution. METHOD: The records of patients with lung cancer were evaluated for adherence to guidelines by using an auditing tool that was developed to capture pertinent information. The study team collected data about the following variables: compliance with documentation of pathological diagnosis, documentation of disease stage prior to treatment initiation, presentation at thoracic tumour board within 30 days of diagnosis, management course, and management of end of life in terms of early ‘no code’ initiation, stopping chemotherapy and referral to palliative care prior to 2 weeks of death. Annual audits were performed from 2012 to 2015. Education and discussion with team members to address the deviations were the main interventions to improve adherence. RESULTS: The baseline measurements were taken in 2012 (49 patients). Histological subtype identification improved from 94% to 100%. Presentation of new cases at the tumour board improved from 35% to 82%. Testing for epidermal growth factor receptor mutation for non-squamous cell lung cancer improved from 77% to 100%. The staging was documented in 100% of the cases. CONCLUSION: Running audits to monitor adherence to guidelines and discussions with the team have a positive effect on providing consistent evidence-based care for patients with lung cancer.",2019 Aug 26,"['Jazieh, Abdulrahman', 'Alkaiyat, Mohammad Omar', 'Ali, Yosra', 'Hashim, Mohamed Ahmed', 'Abdelhafiz, Nafisa', 'Al Olayan, Ashwaq']",BMJ Open Qual,,,False
ca97293b281358aefbe9685a223cbe4a597a2c2b,PMC,"Improving adherence to lung cancer guidelines: a quality improvement project that uses chart review, audit and feedback approach",http://dx.doi.org/10.1136/bmjoq-2018-000436,PMC6711445,31523724,CC BY-NC,"INTRODUCTION: The implementation of evidence-based clinical practice guidelines is one of the most effective interventions for improving quality of care. A gap between guidelines and clinical practice often exists, which may result in patients not receiving appropriate care. This project aimed at improving adherence to lung cancer guidelines at our institution. METHOD: The records of patients with lung cancer were evaluated for adherence to guidelines by using an auditing tool that was developed to capture pertinent information. The study team collected data about the following variables: compliance with documentation of pathological diagnosis, documentation of disease stage prior to treatment initiation, presentation at thoracic tumour board within 30 days of diagnosis, management course, and management of end of life in terms of early ‘no code’ initiation, stopping chemotherapy and referral to palliative care prior to 2 weeks of death. Annual audits were performed from 2012 to 2015. Education and discussion with team members to address the deviations were the main interventions to improve adherence. RESULTS: The baseline measurements were taken in 2012 (49 patients). Histological subtype identification improved from 94% to 100%. Presentation of new cases at the tumour board improved from 35% to 82%. Testing for epidermal growth factor receptor mutation for non-squamous cell lung cancer improved from 77% to 100%. The staging was documented in 100% of the cases. CONCLUSION: Running audits to monitor adherence to guidelines and discussions with the team have a positive effect on providing consistent evidence-based care for patients with lung cancer.",2019 Aug 26,"['Jazieh, Abdulrahman', 'Alkaiyat, Mohammad Omar', 'Ali, Yosra', 'Hashim, Mohamed Ahmed', 'Abdelhafiz, Nafisa', 'Al Olayan, Ashwaq']",BMJ Open Qual,,,False
e35295b96d9cee71829be853fe2a43accd1dff37,PMC,Enemy at the Gate,http://dx.doi.org/10.24171/j.phrp.2019.10.4.01,PMC6711719,31497490,CC BY-NC-ND,,2019 Aug,"Cho, Hae-Wol",Osong Public Health Res Perspect,,,True
4b9e5d0ffdac80fba0ea840f8f14e359ad4c43f1,PMC,Risk of Water and Food-Borne Communicable Diseases in Travelers Entering Korea,http://dx.doi.org/10.24171/j.phrp.2019.10.4.03,PMC6711720,31497492,CC BY-NC-ND,"OBJECTIVES: It was supposed to analyze status and affecting factors in water and food-borne communicable disease by screening entrants with diarrhea symptom at the point of entry in Korea METHODS: Symptomatic travelers with water and food-borne communicable diseases who entered Korea were diagnosed by a health declaration and detection of causative agents in water and food using laboratory tests. Among those entered in 2017, the affecting factors in the incidence of communicable diseases among those who had diarrhea at the entry into Korea, were analyzed, with frequency and chi-square test. RESULTS: The number of travel entrants with gastrointestinal communicable diseases increased by 40.19% from 2013 to 2017. The percentage of causative agents of water and food-borne communicable diseases was the highest at 69.2% from July to September. The rate of detection of causative agents of communicable disease pathogens in travelers from Southeast Asia entering Korea was 70.2%, which was higher than people arriving from East Asia and Central Asia (57.5%; p < 0.001). CONCLUSION: The positive ratio of causative agents of water and food-borne communicable diseases was high among travelers that had entered Korea from July to September, with a high number among entrants from Southeast Asia. Based on the positive detection of causative agents, the entry period and countries visited were statistically significant affecting factors (p < 0.001).",2019 Aug,"['Jung, Kyung Sook', 'Jang, Yu Mi', 'Hwang, Ji Hye', 'Park, Gi Jun', 'Son, Tae Jong']",Osong Public Health Res Perspect,,,True
5f56a9b712608c599a21191b06b78bfa70ad523f,PMC,Long non-coding RNA MEG3 attends to morphine-mediated autophagy of HT22 cells through modulating ERK pathway,http://dx.doi.org/10.1080/13880209.2019.1651343,PMC6713166,31433241,CC BY-NC,"Context: Morphine is an alkaloid isolated from the poppy plants. The addiction of morphine is a very serious social issue. Some long non-coding RNAs (lncRNAs) have been proposed to engage in drug addiction. Objective: Whether lncRNA maternally expressed gene 3 (MEG3) attended to morphine-mediated autophagy of mouse hippocampal neuronal HT22 cells was probed. Materials and methods: HT22 cells were subjected to 10 µM morphine for 24 h. Cell autophagy was assessed by measuring LC3-II/LC3-I and Beclin-1 expression. qRT-PCR was carried out to measure MEG3 expression. SiRNA oligoribonucleotides targeting MEG3 (si-MEG3) was transfected to silence MEG3. The orexin1 receptor (OX1R), c-fos, p/t-ERK and p/t-PKC expressions were tested by western blotting. SCH772984 was used as an inhibitor of ERK pathway. Results: Morphine elevated OX1R (2.92 times), c-fos (2.06 times), p/t-ERK (2.04 times) and p/t-PKC (2.4 times), Beclin-1 (3.2 times) and LC3-II/LC3-I (3.96 times) expression in HT22 cells. Moreover, followed by morphine exposure, the MEG3 expression was also elevated in HT22 cells (3.03 times). The silence of MEG3 lowered the Beclin-1 (1.85 times), LC3-II/LC3-I (2.12 times), c-fos (1.39 times) and p/t-ERK (1.44 times) expressions in morphine-treated HT22 cells. Inhibitor of ERK pathway SCH772984 further promoted the influence of MEG3 silence on morphine-caused Beclin-1 (1.97 times) and LC3-II/LC3-I (1.92 times) expressions decreases. Conclusions: Up-regulation of MEG3 attended to the morphine-caused autophagy of HT22 cells might be through elevating c-fos expression and promoting ERK pathway activation. More experiments are also needed in the future to analyse the influence of other lncRNAs in drug addiction.",2019 Aug 21,"['Gao, Shuibo', 'Li, Enyao', 'Gao, Haixia']",Pharm Biol,,,True
8a8d2206e8fa15801497ee0d24618adb7e34b693,PMC,Establishing Appropriate Agency Relationships for Providers in China,http://dx.doi.org/10.1177/0046958019872348,PMC6713957,31455126,CC BY-NC,"Physicians play multiple roles in a health system. They typically serve simultaneously as the agent for patients, for insurers, for their own medical practices, and for the hospital facilities where they practice. Theoretical and empirical results have demonstrated that financial relations among these different stakeholders can affect clinical outcomes as well as the efficiency and quality of care. What are the physicians’ roles as the agents of Chinese patients? The marketization approach of China’s economic reforms since 1978 has made hospitals and physicians profit-driven. Such profit-driven behavior and the financial tie between hospitals and physicians have in turn made physicians more the agents of hospitals rather than of their patients. While this commentary acknowledges physicians’ ethics and their dedication to their patients, it argues that the current physician agency relation in China has created barriers to achieving some of the central goals of current provider-side health care reform efforts. In addition to eliminating existing perverse financial incentives for both hospitals and physicians, the need for which is already agreed upon by numerous scholars, we argue that the success of the ongoing Chinese public hospital reform and of overall health care reform also relies on establishing appropriate physician-hospital agency relations. This commentary proposes 2 essential steps to establish such physician-hospital agency relations: (1) minimize financial ties between senior physicians and tertiary-level public hospitals by establishing a separate reimbursement system for senior physicians, and (2) establishing a comprehensive physician professionalism system underwritten by the Chinese government, professional physician associations, and major health care facilities as well as by physician leadership representatives. Neither of these suggestions is addressed adequately in current health care reform activities.",2019 Aug 27,"['Liu, Yu', 'Saltman, Richard B.']",Inquiry,,,True
0892a219a7caf18088f5e3a331ec01b6912c9188,PMC,"One health approach in Nepal: Scope, opportunities and challenges",http://dx.doi.org/10.1016/j.onehlt.2019.100101,PMC6715885,31485475,CC BY-NC-ND,"One Health (OH) is a collaborative effort to attain optimal health for people, animals and the environment. The concept of OH is still in its infancy in Nepal but is increasingly growing. The Government of Nepal (GoN) has taken some initiatives to tackle burgeoning problems such as antimicrobial resistance, highly pathogenic avian influenza and rabies using OH approach but there are several challenges at the level of implementation. Few non-governmental organizations support GoN to promote an OH approach. The major bottlenecks in implementing OH in Nepal include poor organizational structure to support OH, absence of a legal framework to implement OH, poor coordination among different governmental agencies, insufficient technical expertise, poor data sharing mechanism across sectors, limited budget and poor understanding at political level. We encourage GoN to address these gaps and prioritize the health problems where OH approach would give the best outcome. Institutional and legal frameworks need to be created to effectively implement an OH approach in Nepal. Increasing awareness among policy makers including political leadership and increasing regular government budget for OH activities would be helpful to promote OH in Nepal.",2019 Aug 12,"['Acharya, Krishna Prasad', 'Karki, Surendra', 'Shrestha, Kshitiz', 'Kaphle, Krishna']",One Health,,,False
78dbccb9c48475f599da9922e4ba3f039a224997,PMC,Some One Health based control strategies for the Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1016/j.onehlt.2019.100102,PMC6715958,31485476,CC BY-NC-ND,"The Middle East respiratory syndrome coronavirus (MERS-CoV) presents an ideal example for developing One Health concepts. Dromedary camels are the principal reservoir for the virus. Infected camels shed the virus in body secretions, particularly nasal discharges. MERS-CoV has the potential to remain active in the environment for some time under optimum conditions of temperature and humidity. This shedding sustains the virus in endemic communities and thus contact with camels is considered a major risk factor for human infection. Reducing virus shedding from camels will have a great positive impact on reducing the human risk of infection. Our main objective is to highlight the potential aspects of reducing virus shedding from camels to the environment, thereby reducing the possibility of human infection. We will focus on the potential roles of camel markets, camel shows, importation, transportation and grazing in the amplification and shedding of the virus, providing some novel concepts for the control approaches for the MERS-CoV.",2019 Aug 21,"['Hemida, Maged Gomaa', 'Alnaeem, Abdelmohsen']",One Health,,,False
e52ecf4b22e9dcb340ccf67f0251b5a3f9373f02,PMC,"Epidemiological status of the Middle East respiratory syndrome coronavirus in 2019: an update from January 1 to March 31, 2019",http://dx.doi.org/10.2147/IJGM.S215396,PMC6716594,31692574,CC BY-NC,"PURPOSE: This study represents the current epidemiological status of Middle East respiratory syndrome coronavirus (MERS-CoV) worldwide in the first three months of 2019. PATIENTS AND METHODS: Full details of the MERS-CoV cases available and published in the disease outbreak news on the WHO website were retrieved. Related details of laboratory-confirmed MERS-CoV were extracted and analyzed by standard statistical methods. RESULTS: A total of 107 cases of MERS-CoV, including 18 deaths (overall case fatality rate (CFR), 16.8%; male-specific CFR was 17.5% [14/80] and female-specific CFR was 14.8% [4/27]) were reported to WHO from the National International Health Regulation Focal Points of Saudi Arabia and Oman. The overall mean age was 50±17 years and 80 patients (74.8%) were male. The average time from the onset of the symptoms to the first hospitalization was 3±3.3 days; from the first hospitalization to laboratory confirmation was 3.6±6.5 days; from the onset of symptom to death was 17.5±11.7 days; and the mean length of hospitalization for patients with MERS-CoV was 3.5±3.9 days. Males in comparison to females had a 1.5-fold increased chance (adjusted OR =1.5 [95% CI: 1.3–1.8]) of death related to MERS-CoV infection; 1.05 [95% CI: 1.1–3.3], 1.05 [95% CI: 1.2–2.8] and 1.06 [95% CI: 1.2–2.0] for those who had exposure to camels, camel milk consumption, and close contact with MERS-CoV cases, respectively. Health care workers had 2.4 fold [95% CI: 1.2–3.1] greater odds of death compared to other people. CONCLUSION: The knowledge obtained from this study can contribute to the development of a prevention program and early system warning against MERS-CoV infection.",2019 Aug 26,"['Ahmadzadeh, Jamal', 'Mobaraki, Kazhal']",Int J Gen Med,,,True
887264fa70bfd2130e5ef9089f058332364d6313,PMC,Simultaneous detection of eleven sexually transmitted agents using multiplexed PCR coupled with MALDI-TOF analysis,http://dx.doi.org/10.2147/IDR.S219580,PMC6717854,31695443,CC BY-NC,"PURPOSE: Sexually transmitted infections (STIs), representing a major global health problem, are caused by different microbes, including bacteria, viruses, and protozoa. Unfortunately, infections of different sexually transmitted pathogens often present similar clinical symptoms, so it is almost impossible to distinguish them clinically. Therefore, the aim of the current study was to develop a sensitive, multitarget, and high-throughput method that can detect various agents responsible for STIs. METHODS: We developed and tested a 23-plex PCR coupled with matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) assay (sexually transmitted infection-mass spectrometry, STI-MS) that simultaneously targets 11 different agents, including 8 most common clinical pathogens related to STIs (HSV-1, HSV-2, Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, Trichomonas vaginalis, Mycoplasma genitalium, and Haemophilus ducreyi) and 3 controversial microorganisms as pathogens (Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum). RESULTS: The results showed that the STI-MS approach can accurately detect the expected agents, without cross-reaction with other organisms. The limit of detection of each STI-MS assay was ranged from 1.739 to 10.009 copies/reaction, using probit analyses. The verification rate for each target organism of the STI-MS ranged from a minimum of 89.3% to a maximum of 100%, using conventional assays and ultrasensitive digital PCR to confirm the STI-MS-positive results. To further evaluate the clinical performance of this assay, 241 clinical specimens (124 urethral/cervical swabs and 117 urine) were tested in parallel using the STI-MS assay and monoplex real-time PCR for each agent. The overall validation parameters of STI-MS were extremely high including sensitivity (from 85.7% to 100%), specificity (from 92.3% to 100%), PPV (from 50% to 100%), and NPV (from 99.1% to 100%) for each target. CONCLUSION: STI-MS is a useful high-throughput screening tool for detecting mixed infections of STIs and has great potential for application in large-scale epidemiological programs for specific microorganisms of STI.",2019 Aug 28,"['Xiu, Leshan', 'Zhang, Chi', 'Li, Yamei', 'Wang, Feng', 'Peng, Junping']",Infect Drug Resist,,,True
c123770a0567eeea72f4df1a2004585732e08198,PMC,Virus- and Interferon Alpha-Induced Transcriptomes of Cells from the Microbat Myotis daubentonii,http://dx.doi.org/10.1016/j.isci.2019.08.016,PMC6718828,31465999,CC BY-NC-ND,"Antiviral interferons (IFN-alpha/beta) are possibly responsible for the high tolerance of bats to zoonotic viruses. Previous studies focused on the IFN system of megabats (suborder Yinpterochiroptera). We present statistically robust RNA sequencing (RNA-seq) data on transcriptomes of cells from the “microbat” Myotis daubentonii (suborder Yangochiroptera) responding at 6 and 24 h to either an IFN-inducing virus or treatment with IFN. Our data reveal genes triggered only by virus, either in both humans and Myotis (CCL4, IFNL3, CH25H), or exclusively in Myotis (STEAP4). Myotis cells also express a series of conserved IFN-stimulated genes (ISGs) and an unusually high paralog number of the antiviral ISG BST2 (tetherin) but lack several ISGs that were described for megabats (EMC2, FILIP1, IL17RC, OTOGL, SLC24A1). Also, in contrast to megabats, we detected neither different IFN-alpha subtypes nor an unusually high baseline expression of IFNs. Thus, Yangochiroptera microbats, represented by Myotis, may possess an IFN system with distinctive features.",2019 Aug 10,"['Hölzer, Martin', 'Schoen, Andreas', 'Wulle, Julia', 'Müller, Marcel A.', 'Drosten, Christian', 'Marz, Manja', 'Weber, Friedemann']",iScience,,,False
0f631c3f9ceddcf03d90d552dbc1a7461c3e25db,PMC,Virus- and Interferon Alpha-Induced Transcriptomes of Cells from the Microbat Myotis daubentonii,http://dx.doi.org/10.1016/j.isci.2019.08.016,PMC6718828,31465999,CC BY-NC-ND,"Antiviral interferons (IFN-alpha/beta) are possibly responsible for the high tolerance of bats to zoonotic viruses. Previous studies focused on the IFN system of megabats (suborder Yinpterochiroptera). We present statistically robust RNA sequencing (RNA-seq) data on transcriptomes of cells from the “microbat” Myotis daubentonii (suborder Yangochiroptera) responding at 6 and 24 h to either an IFN-inducing virus or treatment with IFN. Our data reveal genes triggered only by virus, either in both humans and Myotis (CCL4, IFNL3, CH25H), or exclusively in Myotis (STEAP4). Myotis cells also express a series of conserved IFN-stimulated genes (ISGs) and an unusually high paralog number of the antiviral ISG BST2 (tetherin) but lack several ISGs that were described for megabats (EMC2, FILIP1, IL17RC, OTOGL, SLC24A1). Also, in contrast to megabats, we detected neither different IFN-alpha subtypes nor an unusually high baseline expression of IFNs. Thus, Yangochiroptera microbats, represented by Myotis, may possess an IFN system with distinctive features.",2019 Aug 10,"['Hölzer, Martin', 'Schoen, Andreas', 'Wulle, Julia', 'Müller, Marcel A.', 'Drosten, Christian', 'Marz, Manja', 'Weber, Friedemann']",iScience,,,False
aa8a0b3cfa95daea83c1fc448904d6627593bb59,PMC,Survival of mechanically ventilated patients admitted to intensive care units: Results from a tertiary care center between 2016-2018,http://dx.doi.org/10.15537/smj.2019.8.24447,PMC6718855,31423514,CC BY-NC-SA,"OBJECTIVES: To estimate the survival of adult and pediatric patients receiving mechanical ventilation and determine the associated risk factors METHODS: A retrospective cohort study was carried out in the intensive care unit (ICU) at King Abdulaziz Medical City (KAMC) and King Abdullah Children’s Specialist Hospital (KACSH), Riyadh, Saudi Arabia. The analysis includes data from medical records of all patients admitted to ICUs who received mechanical ventilation between 2016-2018. For each patient, potential risk factors were collected. The main outcome of this study was the mortality during the stay in ICU after receiving mechanical ventilation RESULTS: A total of 262 adults and 175 pediatric patients were admitted to ICUs and received mechanical ventilation during the study period. For adult patients, the overall mortality was 37%, with a median survival time of 11 days (interquartile range [IQR] 6-20 days). The main risk factors independently associated with the increased mortality rate were being aged 51-60 (odds ratio [OR] 2.6, 95% confidence interval [CI] 6.7-1.0) and factors related to ICU admission. For the pediatric population, the mortality rate was 17%, with a median survival time of 16 days (IQR 7-37 days). Prematurity with respiratory problems was the main recorded cause of initiation of mechanical ventilation (50% of patients). Neonates who had mechanical ventilation within one month of their birth and were born extremely preterm had a high mortality rate after the initiation of mechanical ventilation. CONCLUSION: Both patient age and the causes of the initiation of mechanical ventilation were influencing the survival of patients who required mechanical ventilation.",2019 Aug,"['Ismaeil, Taha', 'Almutairi, Jawaher', 'Alshaikh, Rema', 'Althobaiti, Zahrah', 'Ismaiel, Yassin', 'Othman, Fatmah']",Saudi Med J,,,True
0322eccb9230a1aad165702457091eb9ae122d55,PMC,"Proceedings of the Food and Drug Administration public workshop on pathogen reduction technologies for blood safety 2018 (Commentary, p. 3026)",http://dx.doi.org/10.1111/trf.15344,PMC6726584,31144334,CC BY-NC-ND,,2019 Sep 29,"['Atreya, Chintamani', 'Glynn, Simone', 'Busch, Michael', 'Kleinman, Steve', 'Snyder, Edward', 'Rutter, Sara', 'AuBuchon, James', 'Flegel, Willy', 'Reeve, David', 'Devine, Dana', 'Cohn, Claudia', 'Custer, Brian', 'Goodrich, Raymond', 'Benjamin, Richard J.', 'Razatos, Anna', 'Cancelas, Jose', 'Wagner, Stephen', 'Maclean, Michelle', 'Gelderman, Monique', 'Cap, Andrew', 'Ness, Paul']",Transfusion,,,True
94d47d45fbe70e69c32aa588b44fbdfc0333751a,PMC,Duty of care and health worker protections in the age of Ebola: lessons from Médecins Sans Frontières,http://dx.doi.org/10.1136/bmjgh-2019-001593,PMC6730573,31543992,CC BY-NC,,2019 Aug 31,"['McDiarmid, Melissa', 'Crestani, Rosa']",BMJ Glob Health,,,True
09d9038625c7a2e0aa27f9f04cd7f4b2d7ec6f11,PMC,Protecting the world from infectious disease threats: now or never,http://dx.doi.org/10.1136/bmjgh-2019-001885,PMC6730581,31543999,CC BY-NC,,2019 Aug 31,"['Shahpar, Cyrus', 'Lee, Christopher T', 'Wilkason, Colby', 'Buissonnière, Marine', 'McClelland, Amanda', 'Frieden, Thomas R']",BMJ Glob Health,,,True
c4c22747c9ab8d0c3b66d8c2d440cf505f492cba,PMC,Integrating mental health into primary care: the policy maker’s perspective and experience in China,,PMC6734950,31508015,CC BY-NC-ND,"In China, ‘community’ was an alien word. Many people used to live in dormitories (Danwei), to which they were assigned by government according to their work units. ‘Dormitory form’ community was closely linked to where people worked, and thus administration and supervision were simple, as was the provision of health services. In each Danwei, a clinic provided basic healthcare not only for its employees but also for the other residents of the dormitory. The old primary care service was based on this. In fact, the ‘golden age’ of community mental healthcare was at that time, when psychiatric hospitals extended their service to communities via the Danwei ’s clinics in the cities and via ‘barefoot doctors’ in the rural areas. Home beds, occupational therapy stations and shelter factories were set up in some cities and mobile mental health teams played important roles in the villages. Although this did not really represent the ‘integration’ of mental health into primary care, it was a good example of maximising the utilisation of the very limited mental health resources by stretching the psychiatric service, using administrative power, and mobilising family members (Shen et al, 1990; Zhang & Yan, 1990; Zhang, 1999).",2010 Jan 1,"['Xin, Yu', 'Jin, Liu', 'Hong, Ma']",Int Psychiatry,,,True
addfc08009d7a0975783d6208103e9c3c2a41d27,PMC,What does the future hold?,http://dx.doi.org/10.4322/acr.2012.001,PMC6735637,31528555,CC BY-NC,,2012 Mar 30,"de Campos, Fernando Peixoto Ferraz",Autops Case Rep,,,True
23115c887d431cd03a4858bd044e41bee07112e6,PMC,A60 Revealing the evolution of virulence in RNA viruses,http://dx.doi.org/10.1093/ve/vez002.059,PMC6735695,,CC BY-NC,"A combination of high rates of mutation and replication, coupled with strong natural selection, ensures that RNA viruses experience rapid genotypic and phenotypic evolution. Such a ‘fast-forward’ evolution enables viruses to rapidly adapt to new host species, evade host immune responses, and to develop resistance to anti-viral drugs. Similarly, rapid evolution allows viruses to attain new levels of virulence, defined as the ability to cause severe disease in hosts. We hypothesize that distinct viral groups share genetic determinants that modulate virulence that have been acquired through convergent evolution. Thus, common patterns reflecting changing virulence-related specific viral groups could be detected. The main goals for this project are (1) to understand how genetic and phenotypic diversity can be generated among different viral groups by analyzing the variation patterns and determining the selective forces behind them (impact in viral fitness) and (2) to understand how fixed mutations can modulate virulence within different viral groups by performing comparison of strains with differing virulence within a longitudinal timescale. The subject of the study is key emerging and re-emerging virus families of medical importance. Such groups include: Coronaviridae (severe acute respiratory syndrome and Middle East respiratory syndrome-associated coronaviruses), Picornaviridae (Hepatitis A virus), Flaviviridae (Yellow fever, West Nile, Hepatitis C, Dengue, and Zika viruses), Togaviridae (Rubella and Chikungunya virus), Bornaviridae (Borna-disease virus), Filoviridae (Ebola and Marburg viruses), Paramyxoviridae (Measles, Nipah, and Hendra viruses), Rhabdoviridae (Lyssaviruses), Arenaviridae (Lassa virus), Bunyaviridae (Hanta- and Crimean-Congo hemorrhagic fever viruses), and Orthomyxoviridae (Influenza A viruses). Viral genomes collected at different time points, different hosts (human and their most closely related animal reservoirs) and different locations will be compiled. Extensive molecular evolutionary analyses will be carried out to infer gene expansion/contraction within groups, rates of evolution, and changes in selection pressure, including the detection of positive selected genes and sites (adaptive evolution). Positively selected sites will be mapped onto the viral protein structures to reveal their impact on function, and hence the location of potential virulence determinants. Virulence changes among particular viral strains and types will be defined and measured according to definitions based on an increase in: (1) transmissibility, (2) host tropism, (3) immune evasion, (4) morbidity and mortality, (5) drug resistance, and by the incorporation of epidemiological data to determine whether high or low virulence strains within different hosts and localities are spreading most efficiently in nature.",2019 Aug 22,"['Escalera-Zamudio, Marina', 'Gutiérrez, Bernardo', 'Thézé, Julien', 'Pybus, Oliver G']",Virus Evol,,,False
35ddb96aa2fff1f58927be76f4571f3aad757fb2,PMC,A48 Identification and full-genome characterization of Alpha- and Beta-Coronaviruses viruses from bats in Italy,http://dx.doi.org/10.1093/ve/vez002.047,PMC6735706,,CC BY-NC,"Bats are the natural reservoir of Coronaviruses (CoVs). Human CoVs cause mild respiratory diseases worldwide, but, in the last decade, two Beta-CoVs [Middle East respiratory syndrome (MERS)-CoV and severe acute respiratory syndrome] caused thousands of deaths and cases worldwide. Phylogenetic analysis suggested the evolutionary origin of mammalian CoVs is derived from bats. In this study, we characterized three Alpha-CoVs and two Beta-CoVs demonstrating the circulation of bat strains in Italy. Isolates were sequenced using a next-generation sequencing approach and genomes reconstructed using the online tool Galaxy Aries. Phylogenetic analyses were conducted using MEGA7 and MrBayes. Similarity plots were generated using SSE v1.2. The structure of the receptor binding domain (RBD) in the S protein was predicted by sequence-homology method using the protein data bank. Bioinformatics analysis permitted the identification of 2 Beta-CoV complete genomes of 30 kb and three Alpha-CoV of 28 kb (named BatCoV-ITA1-5). BatCoV-ITA1 and 2 formed a monophyletic group with MERS-CoV sequences. The comparison of the concatenated domains within ORF1ab confirmed their classification into the MERS-CoV species. The 3D structure of RBD of Italian strains showed two amino acid deletions located in a region corresponding to the external subdomain of MERS-RBD. BatCoV-Ita3 and BatCoV-Ita4/5 were classified into two novel Alpha-CoV species by comparison of concatenated domains within ORF1ab. Due to the high divergence with the Alpha human spike protein strains, it was impossible to establish the protein structure and the potential affinity to human receptor. The Italian strains showed the typical organization of Alpha and Beta-CoVs. We reported two Beta-CoVs closely related to MERS-CoVs from bats belonging to common Italian species (Pipistrellus kuhlii and Hypsugo savii). The analysis of the RBD in the spike protein indicates significant differences from human RBD known to date. The three Alpha-CoV strains were classified into two novel species, confirming the high heterogeneity of CoV strains in bats. Although the studies conducted cannot confirm a risk for humans, surveillance studies are needed to investigate the genetic diversity of CoVs in bats. Because this exceeds what is known for other hosts, it is compatible with bats being the major reservoir of mammalian CoVs.",2019 Aug 22,"['De Sabato, L', 'Vaccari, G', 'Lelli, D', 'Lavazza, A', 'Castrucci, M R', 'Moreno, A']",Virus Evol,,,False
dfc8247f7e483da9a2fde5288447f7052de83128,PMC,A52 MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity,http://dx.doi.org/10.1093/ve/vez002.051,PMC6735769,,CC BY-NC,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of this zoonotic infection. Although MERS-CoV infection is ubiquitous in dromedaries across Africa and the Arabian Peninsula, the continuous appearance of zoonotic MERS cases in humans is confined to the Arabian Peninsula. MERS-CoV from Africa has hitherto been poorly studied. Here, we report the genetic and phenotypic characterization of MERS-CoV from dromedaries in African countries. Phylogenetically, viruses from dromedaries in Africa formed a monophyletic clade, which we have provisionally designated as virus clade C. Molecular dating analyses of MERS-CoV, including clade C viruses, suggests that the ancestral MERS-CoV in dromedaries could have spread to the two continents within a short timeframe. Camel MERS-CoVs from west and north African countries form a subclade (C1) that shares genetic signatures of a major deletion in the accessory gene ORF4b. Compared with human and camel MERS-CoV from Saudi Arabia, virus isolates from Burkina Faso (BF785) and Nigeria (Nig1657) had lower virus replication competence in Calu-3 cells and in ex vivo cultures of human bronchus and lung, and BF785 replicated to lower titer in lungs of human DPP4-transduced mice. However, it is still inconclusive whether ORF4b deletions may lead to the reduced replication competence of BF785 and Nig1657. Genetic and phenotypic differences in West African viruses may be relevant to the zoonotic potential of MERS-CoV.",2019 Aug 22,"['Chu, D K W', 'Hui, K P Y', 'Perera, R A P M', 'Miguel, E', 'Oladipo, J O', 'Traore, A', 'Fassi-Fihri, O', 'Chan, M C W', 'Zhou, Z', 'So, R T Y', 'Chevalier, V', 'Peiris, J S M']",Virus Evol,,,False
b4ce7ea6a5afa5a67052a4493511dc001bfbc75c,PMC,A53 MERS-CoV in East African dromedary camels,http://dx.doi.org/10.1093/ve/vez002.052,PMC6736029,,CC BY-NC,"Human Middle East respiratory syndrome is a zoonotic respiratory disease caused by Middle East respiratory syndrome coronavirus (MERS-CoV) originating from camels in the Arabian Peninsula. While there are a large number of camels in East Africa, often traded to the Arabian Peninsula, no autochthonous human MERS-CoV case is reported in East Africa. Furthermore, there is limited information of MERS-CoV in East Africa. In this study, MERS-CoV in dromedary camels from Ethiopia was detected using RT-qPCR. Next-generation sequencing was used to obtain the full genome of MERS-CoV. MERS-CoV antibodies were also detected through MERS-spike pseudoparticle neutralization assay. Phylogenetic analysis of full-genome sequences and spike-genome antibodies indicates that MERS-CoV in East Africa is genetically distinct from those in the Arabian Peninsula. The results from this study show that MERS-CoV circulating in dromedary camels in East Africa are genetically distinct from those in the Arabian Peninsula. Further studies are needed to evaluate the risk of zoonotic transmission in East Africa.",2019 Aug 22,"['Zhou, Ziqi', 'Chu, Daniel K W', 'Ali, Abraham', 'Demissié, Getnet F', 'Peiris, Malik']",Virus Evol,,,False
0e903662c85e43faeaee3a8508879ff27c81e5dd,PMC,A54 Genomic analysis of camel-HKU23 in Nigeria dromedary camels reveals strain-specific cross-species recombination,http://dx.doi.org/10.1093/ve/vez002.053,PMC6736086,,CC BY-NC,"Coronaviruses (CoVs) are enveloped, single stranded, positive-sense RNA viruses with a large genomic size of 26–32 kilobases. The first human CoV identified in the 1960s was isolated from patients presenting with common cold symptoms. Subsequent epidemic outbreaks of novel zoonotic CoV transmission were reported, examples including HCoV-229E (229E), HCoV-OC43 (OC43), severe acute respiratory syndrome, and Middle East respiratory syndrome (MERS). The ongoing outbreak of MERS in the Middle East is originating from a zoonotic source of dromedary camels. Surveillance later revealed that three CoV species—HCoV-229E (229E), camel-HKU23, and MERS-CoV—were co-circulating in Saudi Arabia dromedary camels. Camel-HKU23 belongs to Group 2a CoV, which also includes human coronavirus OC43, bovine coronavirus, and porcine hemagglutinating encephalomyelitis virus. Recombination, resulting in the generation of different novel genotypes, has been reported previously among these CoVs. Our surveillance of dromedary camels slaughtered in a major abattoir in Nigeria identified camel-HKU23 from nasal swab samples with a prevalence of 2.2 per cent. Phylogenetic analysis showed Nigeria camel-HKU23 is distinct from those previously identified in Saudi Arabia, while still genetically similar, as they share a monophyletic origin. Recombination analysis of Nigeria camel-HKU23 revealed two recombination breakpoints at positions of 22774–24100 base pairs (bp) and 28224–29362 bp. Recombination breakpoint at position 22774, encoding the Group 2a CoV-specific hemagglutinin esterase gene, exhibited high bootstrap support for clustering with RbCoV HKU14, which was previously detected in domestic rabbits in China. The recombination signal is only observed in Nigeria camel-HKU23, suggesting a regional varied evolutionary history of camel-HKU23. Our findings extended the knowledge of the evolutionary relationship among Group 2a CoVs. Further surveillance in other African camels will be important to elucidate the evolution of camel-HKU23.",2019 Aug 22,"['So, R T Y', 'Oladipo, J O', 'Chu, D K W', 'Peiris, M']",Virus Evol,,,False
91bf77728f819af91ffed7f116dd2da12a1bd2a0,PMC,"Occurrence of feline immunodeficiency virus and feline leukaemia virus in Maputo city and province, Mozambique: a pilot study",http://dx.doi.org/10.1177/2055116919870877,PMC6737869,31534776,CC BY-NC,"OBJECTIVES: Feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) are immunosuppressive viruses in cats that increase their susceptibility to zoonotic pathogens. This study aimed to determine the occurrence of one or both viruses, the risk factors associated with infection, and to develop further recommendations. METHODS: This was a cross-sectional study conducted at the Veterinary Faculty of Eduardo Mondlane University, Mozambique, between March and December 2017, in 145 cats. From each of 145 cats, we took 1.5 ml of blood by jugular puncture for detection of antibodies to FIV and FeLV antigens in whole blood using a commercial test kit, DFV Test FeLV/FIV. RESULTS: We found an overall prevalence of 11.0% and 14.5% for FIV antibodies and FeLV antigens, respectively, with four (2.8%) cats coinfected by both pathogens. Male cats were more likely to be infected with FIV (odds ratio [OR] 1.1, 95% confidence interval [CI] 0.3–4.0) compared with female cats. Clinically ill cats were more likely to have a positive result for FeLV antigen infection (OR 18.8, 95% CI 5.2–68.3). Moreover, cats living in suburban areas have a greater chance of a positive result for FeLV infection (OR 3.7, 95% CI 1.4–9.6) compared with cats living in urban areas. CONCLUSIONS AND RELEVANCE: FIV and FeLV occur in cats from Maputo and possibly all over the country. Further studies should be conducted in Mozambique and other African countries to define the burden of both pathogens in cats, coinfection with other zoonotic pathogens and the possible role played by the cats on the transmission of zoonotic and opportunistic diseases to humans.",2019 Sep 10,"['Tchamo, Cesaltina CLM', 'De Rugeriis, Mónica', 'Noormahomed, Emília V']",JFMS Open Rep,,,True
630a6b5851e9d6362eb68f157fa704bfd97f1705,PMC,Distinct mutation in the feline coronavirus spike protein cleavage activation site in a cat with feline infectious peritonitis-associated meningoencephalomyelitis,http://dx.doi.org/10.1177/2055116919856103,PMC6739741,31534775,CC BY-NC,"CASE SUMMARY: This report describes a cat with chronic, progressive, non-painful, non-lateralizing multifocal neurologic clinical signs associated with feline infectious peritonitis (FIP). The cat initially presented as underweight, despite a good appetite, and a complete blood count showed non-regenerative anemia. Three months later the cat was returned having developed ataxia and paraparesis, which then progressed over 2 months to tetraparesis, tail plegia, urinary and fecal incontinence, and titubation. Histologic examination of the tissues with subsequent immunohistochemistry confirmed FIP-associated meningoencephalomyelitis following necropsy. Molecular analysis of the coronavirus spike protein within the tissues identified a specific, functionally relevant amino acid change (R793M), which was only identified in tissues associated with the central nervous system (ie, brain and spinal cord). RELEVANCE AND NOVEL INFORMATION: This case report describes an early presentation of a cat with primarily neurologic FIP, with molecular characterization of the virus within various tissues.",2019 Jun 26,"['André, Nicole M', 'Cossic, Brieuc', 'Davies, Emma', 'Miller, Andrew D', 'Whittaker, Gary R']",JFMS Open Rep,,,True
216dbed8787845bd23a22cc2dd10964aef95fe71,PMC,Innovative Preventive and Resilience Approaches Against Aedes-linked Vector-borne Arboviral Diseases Threat and Epidemics Burden in Gulf Council Countries,http://dx.doi.org/10.5001/omj.2019.73,PMC6745427,31555414,CC BY-NC,"Facing the local and imported borderless Aedes-linked vector-borne viral diseases threat and epidemics burden, the Health Committee of the Gulf Cooperation Council (GCC), including the Saudi Arabian government, announced that all Gulf countries are still free from the threat of a Zika virus epidemic. This article provides a vision of integrated eco-friendly and sustainable behavioral communication change (BCC), biological control preparedness and resilience approaches, and innovations implementation in Saudi Arabia and GCC for the purpose of controlling the threat of Aedes-linked vector-borne viral diseases. Implementing innovative Aedes-linked arboviral preventive and resilient control measures is pivotal in improving community-based surveillance-response systems, BCC multidisciplinary and empowerment methods, and in enhancing community social mobilization and risk communication strategies. Moreover, boosting social, cultural and ecological preparedness, and prompt management approaches are necessary against the threat of local and global zoonotic epidemics and pandemics. Nurturing evidence and proven tick or mosquito vector populations' reduction, planned urbanization, climate change and waste management systems, and implementing data sharing and tailored mitigation solutions are crucial against the persisting Aedes competence and the public health threat of dengue, MERS-CoV, and influenza outbreaks. Sustained investment and ample financial allocation are needed to improve Muslim pilgrimage (Hajj and Umrah mass gathering) including point of entry screening and treatment, community-based education and awareness campaigns, and increasing mosquito vector viral pathogens surveillance interventions. Increasing evidence-based population participation and resilient emergency community preparedness and rapid response programs integration are critical to reduce mosquito breeding sites, dengue, and other arboviral infections.",2019 Sep,"['Tambo, Ernest', 'El Dessouky, Ashraf G.', 'Khater, Emad I.M.']",Oman Med J,,,True
9104c8bed3340e783a7a0a820ff269711f39bc8f,PMC,Nivolumab-induced Myocarditis Successfully Treated with Corticosteroid Therapy: A Case Report and Review of the Literature,http://dx.doi.org/10.2169/internalmedicine.2596-18,PMC6746646,31118387,CC BY-NC-ND,"A 62-year-old man presented to our hospital for the further evaluation and treatment of his back pain, general fatigue, and dyspnea, which had developed 4 days after the 29th administration of nivolumab to treat his lung cancer. Based on his clinical history, elevated serum cardiac enzyme values, and cardiac magnetic resonance (CMR) imaging and myocardial biopsy findings, he was diagnosed with myocarditis induced by nivolumab. Corticosteroid therapy improved his condition, and CMR performed on hospital day 11 also showed remarkable improvement. Although nivolumab-induced myocarditis is rare, cardiologists should consider it when encountering patients treated with such a drug for malignant disease.",2019 Aug 15,"['Matsuo, Keisuke', 'Ishiguro, Takashi', 'Najama, Takatomo', 'Shimizu, Yoshihiko', 'Kobayashi, Yasuhito', 'Mutou, Makoto']",Intern Med,,,True
61c1d57c318f5a10b2d31abd543d55e24d1fa47c,PMC,The impact of global budgeting in Taiwan on inpatients with unexplained fever,http://dx.doi.org/10.1097/MD.0000000000017131,PMC6750349,31517851,CC BY-NC-ND,"Unexplained fever is one of the most common and difficult diagnostic problems faced daily by clinicians. This study evaluated the differences in health service utilization, health care expenditures, and quality of care provided to patients with unexplained fever before and after global budget (GB) implementation in Taiwan. The National Health Insurance Research Database was used for analyzing the health care expenditures and quality of care before and after implementation of the GB system. Patients diagnosed as having unexplained fever during 2000–2001 were recruited; their 2000–2001 and 2004–2005 data were considered baseline and postintervention data, respectively. Data of 259 patients with unexplained fever were analyzed. The mean lengths of stay (LOSs) before and after GB system implementation were 4.22 ± 0.35 days and 5.29 ± 0.70 days, respectively. The mean costs of different health care expenditures before and after implementation of the GB system were as follows: the mean diagnostic, drug, therapy, and total costs increased respectively from New Taiwan Dollar (NT$) 1440.05 ± NT$97.43, NT$3249.90 ± NT$1108.27, NT$421.03 ± NT$100.03, and NT$13,866.77 ± NT$2,114.95 before GB system implementation to NT$2224.34 ± NT$238.36, NT$4272.31 ± NT$1466.90, NT$2217.03 ± NT$672.20, and NT$22,856.41 ± NT$4,196.28 after implementation. The mean rates of revisiting the emergency department within 3 days and readmission within 14 days increased respectively from 10.5% ± 2.7% and 8.3% ± 2.4% before implementation to 6.3% ± 2.2% and 4.0% ± 1.7% after implementation. GB significantly increased LOS and incremental total costs for patients with unexplained fever; but improved the quality of care.",2019 Sep 13,"['Liu, Keh-Sen', 'Yu, Tsung-Fu', 'Wu, Hsing-Ju', 'Lin, Chun-Yi']",Medicine (Baltimore),,,True
570064e6a308ec28efcc76ef74ba3f0e6ea5e5a5,PMC,The perceptions of natural compounds against dipeptidyl peptidase 4 in diabetes: from in silico to in vivo,http://dx.doi.org/10.1177/2040622319875305,PMC6753520,31555430,CC BY-NC,"Dipeptidyl peptidase IV (DPP-4), an incretin glucagon-like peptide-1 (GLP-1) degrading enzyme, contains two forms and it can exert various physiological functions particular in controlling blood glucose through the action of GLP-1. In diabetic use, the DPP-4 inhibitor can block the DDP-4 to attenuate GLP-1 degradation and prolong GLP-1 its action and sensitize insulin activity for the purpose of lowering blood glucose. Nonetheless the adverse effects of DPP-4 inhibitors severely hinder their clinical applications, and notably there is a clinical demand for novel DPP-4 inhibitors from various sources including chemical synthesis, herbs, and plants with fewer side effects. In this review, we highlight various strategies, namely computational biology (in silico), in vitro enzymatic and cell assays, and in vivo animal tests, for seeking natural DPP-4 inhibitors from botanic sources including herbs and plants. The pros and cons of all approaches for new inhibitor candidates or hits will be under discussion.",2019 Sep 19,"['Lin, Shian-Ren', 'Chang, Chia-Hsiang', 'Tsai, May-Jwan', 'Cheng, Henrich', 'Chen, Jian-Chyi', 'Leong, Max K.', 'Weng, Ching-Feng']",Ther Adv Chronic Dis,,,True
6bd9a619434c6c57efe77c253b97c31d98369b02,PMC,Mycoplasma pneumoniaeassociated transverse myelitis presenting as asymmetric flaccid paralysis,http://dx.doi.org/10.4081/cp.2019.1142,PMC6755258,31579494,CC BY-NC,"Acute transverse myelitis is a rare spinal cord inflammatory disorder that manifests as sudden onset of motor, sensory, and autonomic dysfunctions. Here, we report a case of acute transverse myelitis in a 13- year-old boy secondary to Mycoplasma pneumoniae infection. He presented with left facial palsy and contralateral upper extremity weakness without sensory or autonomic changes. The patient was diagnosed with transverse myelitis based on his magnetic resonance imaging findings, although his presentation was mainly motor dysfunction, which is more consistent with acute flaccid paralysis.",2019 Sep 12,"['Salloum, Shafee', 'Goenka, Ajay', 'Ey, Elizabeth']",Clin Pract,,,True
c96cd1e79d3f1ea12887e2b4d9b3347b9ee07137,PMC,Effects of ubiquitin-proteasome inhibitor on the expression levels of TNF-α and TGF-β1 in mice with viral myocarditis,http://dx.doi.org/10.3892/etm.2019.7895,PMC6755415,31555373,CC BY-NC-ND,"Effects of ubiquitin-proteasome system (UPS) inhibitor MG-132 on the expression levels of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in mice with viral myocarditis were investigated to analyze the correlation of myocardial tissue score of mice between TNF-α and TGF-β1. Eighty healthy male SPF mice aged 6 weeks were selected and 20 mice were randomly selected as the blank group. The blank group did not receive any intervention. Mortality rates of each group were recorded and compared on day 8 of modeling, and heart specimens from the remaining mice were histopathologically examined and the expression of mRNA and protein of TNF-α and TGF-β1 in myocardial tissues were detected by western blot analysis. Correlation between mouse myocardial histopathologic scores and expression of protein of TNF-α and TGF-β1 in myocardial tissues, as well as the expression of TNF-α and TGF-β1 in myocardial tissue in VMC mice was analyzed. The expression levels of myocardial histopathological scores, mRNA and protein of TNF-α and TGF-β1 in the blank and control group were significantly lower than those in the VMC and the MG-132 group. The myocardial histopathological scores, mRNA and TNF-α and TGF-β1 protein in the MG-132 group were significantly lower than those in the VMC group (P<0.05). The expression of TNF-α and TGF-β1 protein in myocardial tissues was positively correlated with the pathological score in myocardial tissue of mice (r=0.843, P<0.05; r=0.763, P<0.05), and there was a positive correlation between the expression of TNF-α and TGF-β1 protein in myocardial tissues of VMC mice (r=0.672, P<0.05). UPS inhibitor MG-132, which can significantly alleviate the myocardial injury of VMC mice, reduced the expression of inflammatory factors in myocardial tissues, and improved the survival rate of mice, thus it is a potential new treatment for VMC.",2019 Oct 14,"['Zhang, Hui', 'Yu, Jingbin', 'Sun, Hu', 'Zhao, Yunhe', 'Wang, Jitao', 'Zhang, Juan', 'Meng, Bin']",Exp Ther Med,,,True
7ca300b9a142c9df5da9d660610782ace344a412,PMC,2019 ACVIM Forum Research Report Program,http://dx.doi.org/10.1111/jvim.15593,PMC6766493,,CC BY-NC,,2019 Sep 9 Sep-Oct,,J Vet Intern Med,,,True
d93f7790f05612e0984dba1bf0e720d2771ac304,PMC,Practical use of povidone‐iodine antiseptic in the maintenance of oral health and in the prevention and treatment of common oropharyngeal infections,http://dx.doi.org/10.1111/ijcp.12707,PMC6767541,26249761,CC BY-NC-ND,"AIMS: To better inform medical practitioners on the role of antiseptics in oropharyngeal health and disease, this article focuses on povidone‐iodine (PVP‐I), an established and widely‐available antiseptic agent. METHODOLOGY: Review of the anti‐infective profile, efficacy and safety of PVP‐I in managing common upper respiratory tract infections such as the common cold, influenza and tonsillo‐pharyngitis, as well as oral complications resulting from cancer treatment (oral mucositis), and dental conditions (periodontitis, caries). RESULTS: Antiseptics with broad‐spectrum anti‐infective activity and low resistance potential offer an attractive option in both infection control and prevention. While there is some evidence of benefit of antiseptics in a variety of clinical settings that include dental and oral hygiene, dermatology, oncology, and pulmonology, there appears to be discordance between the evidence‐base and practice. This is especially apparent in the management and prevention of oropharyngeal infections, for which the use of antiseptics varies considerably between clinical practices, and is in marked contrast to their dermal application, where they are extensively used as both a prophylaxis and a treatment of skin and wound infections, thus minimising the use of antibiotics. CONCLUSION: The link between oral and oropharyngeal health status and susceptibility to infection has long been recognised. The high rates of antibiotic misuse and subsequent development of bacterial resistance (e.g. increasing vancomycin‐resistant enterococci (VRE) and methicillin‐resistant Staphylococcus aureus (MRSA)) in large parts of the world, especially across Asia Pacific, highlight the need for identifying alternative antimicrobials that would minimise the use of these medications. This, together with recent large‐scale outbreaks of, for example, avian and swine influenza virus, further underline the importance of an increasing armamentarium for infection prevention and control.",2015 Nov 6,"['Kanagalingam, J.', 'Feliciano, R.', 'Hah, J. H.', 'Labib, H.', 'Le, T. A.', 'Lin, J.‐C.']",Int J Clin Pract,,,True
84d00088f2124eac73c0e79cb15fbe4924109178,PMC,"Molecular Evidence of Influenza A Virus Circulation in African Dromedary Camels Imported to Saudi Arabia, 2017–2018",http://dx.doi.org/10.1093/ofid/ofz370,PMC6767964,31660338,CC BY-NC-ND,"Little is known about influenza A viruses in dromedaries. Here, we detected influenza A viral RNA in 11 specimens (1.7 %) out of 665 nasal swabs collected from dromedaries between 2017 and 2018 in Saudi Arabia. Positive samples were detected only in imported camels from Sudan and Djibouti but not local ones. Partial genome sequencing indicates a close relationship to 2009–2019 human/swine influenza A H1N1 isolates from different countries, suggesting possible interspecies transmission. Taken together, dromedaries could represent a potentially unrecognized permissive host for these viruses, highlighting the need for enhanced surveillance in animals to aid implementation of one-health strategies.",2019 Sep 30,"['Alghamdi, Abdulaziz', 'Hassan, Ahmed M', 'Tolah, Ahmed M', 'Alamari, Sawsan S', 'Alzahrani, Abdulrahman A', 'Alsaaidi, Ghaleb A', 'Abujamel, Turki S', 'Azhar, Esam I', 'Hashem, Anwar M']",Open Forum Infect Dis,,,True
fc9566ce58963eeecb60b3dd52a9e03712045a38,PMC,"Pathology of infectious diseases: new agents, opportunistic, neglectable, emergent, reemergent diseases and why not super resistant nosocomial bacteria?",http://dx.doi.org/10.4322/acr.2019.126,PMC6768261,31641650,CC BY-NC,,2019 Sep 27,"Duarte-Neto, Amaro Nunes",Autops Case Rep,,,True
9a4c0d0a76e1ecd99c5a45fe8ff2a96aeff0fc2b,PMC,Mechanisms and biomedical implications of –1 programmed ribosome frameshifting on viral and bacterial mRNAs,http://dx.doi.org/10.1002/1873-3468.13478,PMC6771820,31222875,CC BY-NC,"Some proteins are expressed as a result of a ribosome frameshifting event that is facilitated by a slippery site and downstream secondary structure elements in the mRNA. This review summarizes recent progress in understanding mechanisms of –1 frameshifting in several viral genes, including IBV 1a/1b, HIV‐1 gag‐pol, and SFV 6K, and in Escherichia coli dnaX. The exact frameshifting route depends on the availability of aminoacyl‐tRNAs: the ribosome normally slips into the –1‐frame during tRNA translocation, but can also frameshift during decoding at condition when aminoacyl‐tRNA is in limited supply. Different frameshifting routes and additional slippery sites allow viruses to maintain a constant production of their key proteins. The emerging idea that tRNA pools are important for frameshifting provides new direction for developing antiviral therapies.",2019 Jul 20,"['Korniy, Natalia', 'Samatova, Ekaterina', 'Anokhina, Maria M.', 'Peske, Frank', 'Rodnina, Marina V.']",FEBS Lett,,,True
53f05daf7342372ab5fbeb2f4f5710254fcad893,PMC,How law can help solve the collective action problem of antimicrobial resistance,http://dx.doi.org/10.1111/bioe.12597,PMC6771835,31268565,CC BY-NC,Antimicrobial resistance is a global collective action problem with dire consequences for human health. This article considers how domestic and international legal mechanisms can be used to address antimicrobial resistance and overcome the governance and political economy challenges that accelerate it.,2019 Sep 3,"['Hoffman, Steven J.', 'Bakshi, Reema', 'Rogers Van Katwyk, Susan']",Bioethics,,,True
c3df72b290828f12274a34ec6f4ca15d17d885de,PMC,Using population-wide administrative and laboratory data to estimate type- and subtype-specific influenza vaccine effectiveness: a surveillance protocol,http://dx.doi.org/10.1136/bmjopen-2019-029708,PMC6773297,31575570,CC BY-NC,"INTRODUCTION: The appropriateness of using routinely collected laboratory data combined with administrative data for estimating influenza vaccine effectiveness (VE) is still being explored. This paper outlines a protocol to estimate influenza VE using linked laboratory and administrative data which could act as a companion to estimates derived from other methods. METHODS AND ANALYSIS: We will use the test-negative design to estimate VE for each influenza type/subtype and season. Province-wide individual-level records of positive and negative influenza tests at the Provincial Laboratory for Public Health in Alberta will be linked, by unique personal health numbers, to administrative databases and vaccination records held at the Ministry of Health in Alberta to determine covariates and influenza vaccination status, respectively. Covariates of interests include age, sex, immunocompromising chronic conditions and healthcare setting. Cases will be defined based on an individual’s first positive influenza test during the season, and potential controls will be defined based on an individual’s first negative influenza test during the season. One control for each case will be randomly selected based on the week the specimen was collected. We will estimate VE using multivariable logistic regression. ETHICS AND DISSEMINATION: Ethics approval was obtained from the University of Alberta’s Health Research Ethics Board—Health Panel under study ID Pro00075997. Results will be disseminated by public health officials in Alberta.",2019 Sep 30,"['Scott, Allison Nicole', 'Buchan, Sarah A', 'Kwong, Jeffrey C', 'Drews, Steven J', 'Simmonds, Kimberley A', 'Svenson, Lawrence W']",BMJ Open,,,True
eed4463e9a2c736a3e76c379689d2aca6247981e,PMC,Using population-wide administrative and laboratory data to estimate type- and subtype-specific influenza vaccine effectiveness: a surveillance protocol,http://dx.doi.org/10.1136/bmjopen-2019-029708,PMC6773297,31575570,CC BY-NC,"INTRODUCTION: The appropriateness of using routinely collected laboratory data combined with administrative data for estimating influenza vaccine effectiveness (VE) is still being explored. This paper outlines a protocol to estimate influenza VE using linked laboratory and administrative data which could act as a companion to estimates derived from other methods. METHODS AND ANALYSIS: We will use the test-negative design to estimate VE for each influenza type/subtype and season. Province-wide individual-level records of positive and negative influenza tests at the Provincial Laboratory for Public Health in Alberta will be linked, by unique personal health numbers, to administrative databases and vaccination records held at the Ministry of Health in Alberta to determine covariates and influenza vaccination status, respectively. Covariates of interests include age, sex, immunocompromising chronic conditions and healthcare setting. Cases will be defined based on an individual’s first positive influenza test during the season, and potential controls will be defined based on an individual’s first negative influenza test during the season. One control for each case will be randomly selected based on the week the specimen was collected. We will estimate VE using multivariable logistic regression. ETHICS AND DISSEMINATION: Ethics approval was obtained from the University of Alberta’s Health Research Ethics Board—Health Panel under study ID Pro00075997. Results will be disseminated by public health officials in Alberta.",2019 Sep 30,"['Scott, Allison Nicole', 'Buchan, Sarah A', 'Kwong, Jeffrey C', 'Drews, Steven J', 'Simmonds, Kimberley A', 'Svenson, Lawrence W']",BMJ Open,,,True
02d9be8cdb8499cd90f2c9cee8421b02b2bbba76,PMC,Using population-wide administrative and laboratory data to estimate type- and subtype-specific influenza vaccine effectiveness: a surveillance protocol,http://dx.doi.org/10.1136/bmjopen-2019-029708,PMC6773297,31575570,CC BY-NC,"INTRODUCTION: The appropriateness of using routinely collected laboratory data combined with administrative data for estimating influenza vaccine effectiveness (VE) is still being explored. This paper outlines a protocol to estimate influenza VE using linked laboratory and administrative data which could act as a companion to estimates derived from other methods. METHODS AND ANALYSIS: We will use the test-negative design to estimate VE for each influenza type/subtype and season. Province-wide individual-level records of positive and negative influenza tests at the Provincial Laboratory for Public Health in Alberta will be linked, by unique personal health numbers, to administrative databases and vaccination records held at the Ministry of Health in Alberta to determine covariates and influenza vaccination status, respectively. Covariates of interests include age, sex, immunocompromising chronic conditions and healthcare setting. Cases will be defined based on an individual’s first positive influenza test during the season, and potential controls will be defined based on an individual’s first negative influenza test during the season. One control for each case will be randomly selected based on the week the specimen was collected. We will estimate VE using multivariable logistic regression. ETHICS AND DISSEMINATION: Ethics approval was obtained from the University of Alberta’s Health Research Ethics Board—Health Panel under study ID Pro00075997. Results will be disseminated by public health officials in Alberta.",2019 Sep 30,"['Scott, Allison Nicole', 'Buchan, Sarah A', 'Kwong, Jeffrey C', 'Drews, Steven J', 'Simmonds, Kimberley A', 'Svenson, Lawrence W']",BMJ Open,,,True
f5f51b4ecc1f2d630d1ecca8329ce8a8177dfbe4,PMC,Using population-wide administrative and laboratory data to estimate type- and subtype-specific influenza vaccine effectiveness: a surveillance protocol,http://dx.doi.org/10.1136/bmjopen-2019-029708,PMC6773297,31575570,CC BY-NC,"INTRODUCTION: The appropriateness of using routinely collected laboratory data combined with administrative data for estimating influenza vaccine effectiveness (VE) is still being explored. This paper outlines a protocol to estimate influenza VE using linked laboratory and administrative data which could act as a companion to estimates derived from other methods. METHODS AND ANALYSIS: We will use the test-negative design to estimate VE for each influenza type/subtype and season. Province-wide individual-level records of positive and negative influenza tests at the Provincial Laboratory for Public Health in Alberta will be linked, by unique personal health numbers, to administrative databases and vaccination records held at the Ministry of Health in Alberta to determine covariates and influenza vaccination status, respectively. Covariates of interests include age, sex, immunocompromising chronic conditions and healthcare setting. Cases will be defined based on an individual’s first positive influenza test during the season, and potential controls will be defined based on an individual’s first negative influenza test during the season. One control for each case will be randomly selected based on the week the specimen was collected. We will estimate VE using multivariable logistic regression. ETHICS AND DISSEMINATION: Ethics approval was obtained from the University of Alberta’s Health Research Ethics Board—Health Panel under study ID Pro00075997. Results will be disseminated by public health officials in Alberta.",2019 Sep 30,"['Scott, Allison Nicole', 'Buchan, Sarah A', 'Kwong, Jeffrey C', 'Drews, Steven J', 'Simmonds, Kimberley A', 'Svenson, Lawrence W']",BMJ Open,,,False
2dc628f8092de38b705b1c159ef93a45425f9643,PMC,B-cell restriction – an alternative piece to the puzzle,http://dx.doi.org/10.1080/21645515.2019.1600989,PMC6773388,30945969,CC BY-NC-ND,"Effective vaccination is based on three critical aspects of the B-cell response towards infectious agents: (i) that B-cells can generate specific antibodies towards a vast molecular diversity of antigens; proteins, sugars, DNA and lipids. There seems to be no limit to the ability to raise antibodies to everything. (ii) once stimulated, B-cells can perfect their antibodies through affinity maturation to complement every nook and cranny of the epitope and (iii) that the pathogen remains genetically stable and does not change to any great extent. Thus, antibodies produced against the vaccine and subsequent boosts recognize the viral virulent field isolates in future encounters and effectively knock them out. However, some vaccine targets, such as flu virus and HIV, are extremely genetically dynamic. The rapid genetic drift of these viruses renders them moving targets which assist in their ability to evade immune surveillance. Here we postulate that in the case of hyper-variable pathogens the B-cell response actually might be “too good”. We propose that restricting B-cell activities may prove effective in counteracting the genetic diversity of variant viruses such as flu and HIV. We suggest two levels of “B-cell restriction”: (i) to focus the B-cell response exclusively towards neutralizing epitopes by creating epitope-based immunogens; (ii) to restrict affinity maturation of B-cells to prevent the production of overly optimized exquisitely specific antibodies. Together, these “B-cell restrictions” provide a new modality for vaccine design.",2019 Apr 23,"Gershoni, Jonathan M.",Hum Vaccin Immunother,,,True
2d1300359d8ec1682b0b6bdb51df4604a7ed4930,PMC,Epidemiological and clinical profile of Korean travelers receiving international medical repatriation,http://dx.doi.org/10.1097/MD.0000000000017330,PMC6775375,31574869,CC BY-NC,"The aim of this study was to investigate the experiences of medical transportation of Korean travelers who suffered accidents abroad and then transferred home by our aeromedical team. We collected demographic and clinical data on patients injured while traveling abroad from January 2013 to July 2017. Descriptive analyses based on 4 different transportation methods and transport time since hospitalization were performed. A total of 33 patients were repatriated during the study period. Of these, 28 (84.8%) were trauma cases with pedestrian injuries being the most common (11 cases; 39.3%). Twenty patients were repatriated by flight-stretchers, 6 by flight-prestige, 2 by ship, and 5 by air ambulance. The air ambulance was the most expensive (average 61,124 US Dollars) mode of transportation (P = .001) and the ship took the longest time (14 hours) to transport patients back to Korea from regions with similar distance (P = .0023). We experienced medical repatriation of 33 seriously injured Korean travelers back to South Korea. Transfer time should be an important considering factor and directly contacting and communicating with the specialized staff of foreign hospitals could also be very important to reduce unnecessary overseas hospital stay and cost incidence.",2019 Sep 27,"['Kim, Jiena', 'Choi, Hyo Jeong', 'Kim, Ho Jung']",Medicine (Baltimore),,,True
2e16617b3004017c0f1c2fcbb140d70444fee083,PMC,Characteristics and Outcomes of Patients with Pulmonary Acute Respiratory Distress Syndrome Infected with Influenza versus Other Respiratory Viruses,http://dx.doi.org/10.4046/trd.2019.0017,PMC6778745,31583874,CC BY-NC,"BACKGROUND: Although the frequency of respiratory viral infection in patients with pulmonary acute respiratory distress syndrome (ARDS) is not uncommon, clinical significance of the condition remains to be further elucidated. The purpose of this study was to compare characteristics and outcomes of patients with pulmonary ARDS infected with influenza and other respiratory viruses. METHODS: Clinical data of patients with pulmonary ARDS infected with respiratory viruses January 2014–June 2018 were reviewed. Respiratory viral infection was identified by multiplex reverse transcription–polymerase chain reaction (RT-PCR). RESULTS: Among 126 patients who underwent multiplex RT-PCR, respiratory viral infection was identified in 46% (58/126): 28 patients with influenza and 30 patients with other respiratory viruses. There was no significant difference in baseline and clinical characteristics between patients with influenza and those with other respiratory viruses. The use of extracorporeal membrane oxygenation (ECMO) was more frequent in patients with influenza than in those with other respiratory viruses (32.1% vs 3.3%, p=0.006). Co-bacterial pathogens were more frequently isolated from respiratory samples of patients with pulmonary ARDS infected with influenza virus than those with other respiratory viruses. (53.6% vs 26.7%, p=0.036). There were no significant differences regarding clinical outcomes. In multivariate analysis, acute physiology and chronic health evaluation II was associated with 30-mortality (odds ratio, 1.158; 95% confidence interval, 1.022–1.312; p=0.022). CONCLUSION: Respiratory viral infection was not uncommon in patients with pulmonary ARDS. Influenza virus was most commonly identified and was associated with more co-bacterial infection and ECMO therapy.",2019 Oct 30,"['Yoo, Jung-Wan', 'Ju, Sunmi', 'Lee, Seung Jun', 'Cho, Min-Chul', 'Cho, Yu Ji', 'Jeong, Yi Yeong', 'Lee, Jong Deog', 'Kim, Ho Choel']",Tuberc Respir Dis (Seoul),,,True
45cf4bcdf80e9ed9e3048485b0c57926028451d3,PMC,Novel Therapeutic Approaches Targeting the Renin-Angiotensin System and Associated Peptides in Hypertension and Heart Failure,http://dx.doi.org/10.1124/pr.118.017129,PMC6782023,31537750,CC BY-NC,"Despite the success of renin-angiotensin system (RAS) blockade by angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor (AT(1)R) blockers, current therapies for hypertension and related cardiovascular diseases are still inadequate. Identification of additional components of the RAS and associated vasoactive pathways, as well as new structural and functional insights into established targets, have led to novel therapeutic approaches with the potential to provide improved cardiovascular protection and better blood pressure control and/or reduced adverse side effects. The simultaneous modulation of several neurohumoral mediators in key interconnected blood pressure–regulating pathways has been an attractive approach to improve treatment efficacy, and several novel approaches involve combination therapy or dual-acting agents. In addition, increased understanding of the complexity of the RAS has led to novel approaches aimed at upregulating the ACE2/angiotensin-(1-7)/Mas axis to counter-regulate the harmful effects of the ACE/angiotensin II/angiotensin III/AT(1)R axis. These advances have opened new avenues for the development of novel drugs targeting the RAS to better treat hypertension and heart failure. Here we focus on new therapies in preclinical and early clinical stages of development, including novel small molecule inhibitors and receptor agonists/antagonists, less conventional strategies such as gene therapy to suppress angiotensinogen at the RNA level, recombinant ACE2 protein, and novel bispecific designer peptides.",2019 Oct,"['Arendse, Lauren B.', 'Danser, A. H. Jan', 'Poglitsch, Marko', 'Touyz, Rhian M.', 'Burnett, John C.', 'Llorens-Cortes, Catherine', 'Ehlers, Mario R.', 'Sturrock, Edward D.']",Pharmacol Rev,,,True
ddf5a29103d06a6ab0fef7f8c15c169050e493c2,PMC,A Retrospective Study Investigating Risks of Acute Respiratory Distress Syndrome and Mortality Following Human Metapneumovirus Infection in Hospitalized Adults,http://dx.doi.org/10.4266/kjccm.2017.00038,PMC6786705,31723632,CC BY-NC,"BACKGROUND: Human metapneumovirus (hMPV) is a relatively recently identified respiratory virus that induces respiratory symptoms similar to those of respiratory syncytial virus infection in children. The characteristics of hMPV-infected adults are unclear because few cases have been reported. METHODS: We conducted a retrospective review of hospitalized adult patients with a positive multiplex real-time polymerase chain reaction assay result from 2012 to 2016 at a single tertiary referral hospital in South Korea. We analyzed clinical characteristics of the enrolled patients and divided patients into an acute respiratory distress syndrome (ARDS) group and a non-ARDS group. RESULTS: In total, 110 adults were reviewed in this study. Their mean age was 61.4 years, and the majority (n = 105, 95.5%) had comorbidities or were immunocompromised. Most of the patients had pneumonia on chest X-ray (n = 88, 93.6%), 22 (20.0%) had ARDS, and 12 (10.9%) expired during hospitalization. The mortality rate for patients with ARDS was higher than that of the other patients (36.4% vs. 5.7%, P = 0.001). The risk factor for hMPV-associated ARDS was heart failure (odds ratio, 5.24; P = 0.044) and laboratory values were increased blood urea nitrogen and increased C-reactive protein. The acquisition site of infection was divided into community vs. nosocomial; 43 patients (39.1%) had a nosocomial infection. The risk factors for nosocomial infection were an immunocompromised state, malignancy and immunosuppressive treatment. CONCLUSIONS: These data suggest that hMPV is one of the important respiratory pathogens important respiratory pathogen that causes pneumonia/ARDS in elderly, immunocompromised individuals and that it may be transmitted via the nosocomial route.",2017 May 31,"['Hwang, Hyunjung', 'Kim, Yujin', 'Park, Jeong-Woong', 'Jeong, Sung Hwan', 'Kyung, Sun Young']",Korean J Crit Care Med,,,True
1f2db689c7aab2b23d60c6da16731d54efe0612f,PMC,A Retrospective Study Investigating Risks of Acute Respiratory Distress Syndrome and Mortality Following Human Metapneumovirus Infection in Hospitalized Adults,http://dx.doi.org/10.4266/kjccm.2017.00038,PMC6786705,31723632,CC BY-NC,"BACKGROUND: Human metapneumovirus (hMPV) is a relatively recently identified respiratory virus that induces respiratory symptoms similar to those of respiratory syncytial virus infection in children. The characteristics of hMPV-infected adults are unclear because few cases have been reported. METHODS: We conducted a retrospective review of hospitalized adult patients with a positive multiplex real-time polymerase chain reaction assay result from 2012 to 2016 at a single tertiary referral hospital in South Korea. We analyzed clinical characteristics of the enrolled patients and divided patients into an acute respiratory distress syndrome (ARDS) group and a non-ARDS group. RESULTS: In total, 110 adults were reviewed in this study. Their mean age was 61.4 years, and the majority (n = 105, 95.5%) had comorbidities or were immunocompromised. Most of the patients had pneumonia on chest X-ray (n = 88, 93.6%), 22 (20.0%) had ARDS, and 12 (10.9%) expired during hospitalization. The mortality rate for patients with ARDS was higher than that of the other patients (36.4% vs. 5.7%, P = 0.001). The risk factor for hMPV-associated ARDS was heart failure (odds ratio, 5.24; P = 0.044) and laboratory values were increased blood urea nitrogen and increased C-reactive protein. The acquisition site of infection was divided into community vs. nosocomial; 43 patients (39.1%) had a nosocomial infection. The risk factors for nosocomial infection were an immunocompromised state, malignancy and immunosuppressive treatment. CONCLUSIONS: These data suggest that hMPV is one of the important respiratory pathogens important respiratory pathogen that causes pneumonia/ARDS in elderly, immunocompromised individuals and that it may be transmitted via the nosocomial route.",2017 May 31,"['Hwang, Hyunjung', 'Kim, Yujin', 'Park, Jeong-Woong', 'Jeong, Sung Hwan', 'Kyung, Sun Young']",Korean J Crit Care Med,,,False
af6f879247d84fabc9201446a9ee97e5573038ac,PMC,A Retrospective Study Investigating Risks of Acute Respiratory Distress Syndrome and Mortality Following Human Metapneumovirus Infection in Hospitalized Adults,http://dx.doi.org/10.4266/kjccm.2017.00038,PMC6786705,31723632,CC BY-NC,"BACKGROUND: Human metapneumovirus (hMPV) is a relatively recently identified respiratory virus that induces respiratory symptoms similar to those of respiratory syncytial virus infection in children. The characteristics of hMPV-infected adults are unclear because few cases have been reported. METHODS: We conducted a retrospective review of hospitalized adult patients with a positive multiplex real-time polymerase chain reaction assay result from 2012 to 2016 at a single tertiary referral hospital in South Korea. We analyzed clinical characteristics of the enrolled patients and divided patients into an acute respiratory distress syndrome (ARDS) group and a non-ARDS group. RESULTS: In total, 110 adults were reviewed in this study. Their mean age was 61.4 years, and the majority (n = 105, 95.5%) had comorbidities or were immunocompromised. Most of the patients had pneumonia on chest X-ray (n = 88, 93.6%), 22 (20.0%) had ARDS, and 12 (10.9%) expired during hospitalization. The mortality rate for patients with ARDS was higher than that of the other patients (36.4% vs. 5.7%, P = 0.001). The risk factor for hMPV-associated ARDS was heart failure (odds ratio, 5.24; P = 0.044) and laboratory values were increased blood urea nitrogen and increased C-reactive protein. The acquisition site of infection was divided into community vs. nosocomial; 43 patients (39.1%) had a nosocomial infection. The risk factors for nosocomial infection were an immunocompromised state, malignancy and immunosuppressive treatment. CONCLUSIONS: These data suggest that hMPV is one of the important respiratory pathogens important respiratory pathogen that causes pneumonia/ARDS in elderly, immunocompromised individuals and that it may be transmitted via the nosocomial route.",2017 May 31,"['Hwang, Hyunjung', 'Kim, Yujin', 'Park, Jeong-Woong', 'Jeong, Sung Hwan', 'Kyung, Sun Young']",Korean J Crit Care Med,,,False
25c88fafba786f31d034614ba0f6efce5c687594,PMC,Rapid Response Systems Reduce In-Hospital Cardiopulmonary Arrest: A Pilot Study and Motivation for a Nationwide Survey,http://dx.doi.org/10.4266/kjccm.2017.00024,PMC6786727,31723641,CC BY-NC,"BACKGROUND: Early recognition of the signs and symptoms of clinical deterioration could diminish the incidence of cardiopulmonary arrest. The present study investigates outcomes with respect to cardiopulmonary arrest rates in institutions with and without rapid response systems (RRSs) and the current level of cardiopulmonary arrest rate in tertiary hospitals. METHODS: This was a retrospective study based on data from 14 tertiary hospitals. Cardiopulmonary resuscitation (CPR) rate reports were obtained from each hospital to include the number of cardiopulmonary arrest events in adult patients in the general ward, the annual adult admission statistics, and the structure of the RRS if present. RESULTS: Hospitals with RRSs showed a statistically significant reduction of the CPR rate between 2013 and 2015 (odds ratio [OR], 0.731; 95% confidence interval [CI], 0.577 to 0.927; P = 0.009). Nevertheless, CPR rates of 2013 and 2015 did not change in hospitals without RRS (OR, 0.988; 95% CI, 0.868 to 1.124; P = 0.854). National university-affiliated hospitals showed less cardiopulmonary arrest rate than private university-affiliated in 2015 (1.92 vs. 2.40; OR, 0.800; 95% CI, 0.702 to 0.912; P = 0.001). High-volume hospitals showed lower cardiopulmonary arrest rates compared with medium-volume hospitals in 2013 (1.76 vs. 2.63; OR, 0.667; 95% CI, 0.577 to 0.772; P < 0.001) and in 2015 (1.55 vs. 3.20; OR, 0.485; 95% CI, 0.428 to 0.550; P < 0.001). CONCLUSIONS: RRSs may be a feasible option to reduce the CPR rate. The discrepancy in cardiopulmonary arrest rates suggests further research should include a nationwide survey to tease out factors involved in in-hospital cardiopulmonary arrest and differences in outcomes based on hospital characteristics.",2017 Aug 31,"['Park, Yeonhee', 'Ahn, Jong-Joon', 'Kang, Byung Ju', 'Lee, Young Seok', 'Ha, Sang-Ook', 'Min, Jin-Soo', 'Cho, Woo-Hyun', 'Na, Se-Hee', 'Lee, Dong-Hyun', 'Park, Seung-Yong', 'Hong, Goo-Hyeon', 'Kim, Hyun-Jung', 'Shim, Sangwoo', 'Kim, Jung-Hyun', 'Lee, Seok-Jeong', 'Park, So-Young', 'Moon, Jae Young']",Korean J Crit Care Med,,,True
e918fa86b48ad310a58f1c7aa0ba307fa97c66e9,PMC,Rapid Response Systems Reduce In-Hospital Cardiopulmonary Arrest: A Pilot Study and Motivation for a Nationwide Survey,http://dx.doi.org/10.4266/kjccm.2017.00024,PMC6786727,31723641,CC BY-NC,"BACKGROUND: Early recognition of the signs and symptoms of clinical deterioration could diminish the incidence of cardiopulmonary arrest. The present study investigates outcomes with respect to cardiopulmonary arrest rates in institutions with and without rapid response systems (RRSs) and the current level of cardiopulmonary arrest rate in tertiary hospitals. METHODS: This was a retrospective study based on data from 14 tertiary hospitals. Cardiopulmonary resuscitation (CPR) rate reports were obtained from each hospital to include the number of cardiopulmonary arrest events in adult patients in the general ward, the annual adult admission statistics, and the structure of the RRS if present. RESULTS: Hospitals with RRSs showed a statistically significant reduction of the CPR rate between 2013 and 2015 (odds ratio [OR], 0.731; 95% confidence interval [CI], 0.577 to 0.927; P = 0.009). Nevertheless, CPR rates of 2013 and 2015 did not change in hospitals without RRS (OR, 0.988; 95% CI, 0.868 to 1.124; P = 0.854). National university-affiliated hospitals showed less cardiopulmonary arrest rate than private university-affiliated in 2015 (1.92 vs. 2.40; OR, 0.800; 95% CI, 0.702 to 0.912; P = 0.001). High-volume hospitals showed lower cardiopulmonary arrest rates compared with medium-volume hospitals in 2013 (1.76 vs. 2.63; OR, 0.667; 95% CI, 0.577 to 0.772; P < 0.001) and in 2015 (1.55 vs. 3.20; OR, 0.485; 95% CI, 0.428 to 0.550; P < 0.001). CONCLUSIONS: RRSs may be a feasible option to reduce the CPR rate. The discrepancy in cardiopulmonary arrest rates suggests further research should include a nationwide survey to tease out factors involved in in-hospital cardiopulmonary arrest and differences in outcomes based on hospital characteristics.",2017 Aug 31,"['Park, Yeonhee', 'Ahn, Jong-Joon', 'Kang, Byung Ju', 'Lee, Young Seok', 'Ha, Sang-Ook', 'Min, Jin-Soo', 'Cho, Woo-Hyun', 'Na, Se-Hee', 'Lee, Dong-Hyun', 'Park, Seung-Yong', 'Hong, Goo-Hyeon', 'Kim, Hyun-Jung', 'Shim, Sangwoo', 'Kim, Jung-Hyun', 'Lee, Seok-Jeong', 'Park, So-Young', 'Moon, Jae Young']",Korean J Crit Care Med,,,False
e918fa86b48ad310a58f1c7aa0ba307fa97c66e9,PMC,Rapid Response Systems Reduce In-Hospital Cardiopulmonary Arrest: A Pilot Study and Motivation for a Nationwide Survey,http://dx.doi.org/10.4266/kjccm.2017.00024,PMC6786727,31723641,CC BY-NC,"BACKGROUND: Early recognition of the signs and symptoms of clinical deterioration could diminish the incidence of cardiopulmonary arrest. The present study investigates outcomes with respect to cardiopulmonary arrest rates in institutions with and without rapid response systems (RRSs) and the current level of cardiopulmonary arrest rate in tertiary hospitals. METHODS: This was a retrospective study based on data from 14 tertiary hospitals. Cardiopulmonary resuscitation (CPR) rate reports were obtained from each hospital to include the number of cardiopulmonary arrest events in adult patients in the general ward, the annual adult admission statistics, and the structure of the RRS if present. RESULTS: Hospitals with RRSs showed a statistically significant reduction of the CPR rate between 2013 and 2015 (odds ratio [OR], 0.731; 95% confidence interval [CI], 0.577 to 0.927; P = 0.009). Nevertheless, CPR rates of 2013 and 2015 did not change in hospitals without RRS (OR, 0.988; 95% CI, 0.868 to 1.124; P = 0.854). National university-affiliated hospitals showed less cardiopulmonary arrest rate than private university-affiliated in 2015 (1.92 vs. 2.40; OR, 0.800; 95% CI, 0.702 to 0.912; P = 0.001). High-volume hospitals showed lower cardiopulmonary arrest rates compared with medium-volume hospitals in 2013 (1.76 vs. 2.63; OR, 0.667; 95% CI, 0.577 to 0.772; P < 0.001) and in 2015 (1.55 vs. 3.20; OR, 0.485; 95% CI, 0.428 to 0.550; P < 0.001). CONCLUSIONS: RRSs may be a feasible option to reduce the CPR rate. The discrepancy in cardiopulmonary arrest rates suggests further research should include a nationwide survey to tease out factors involved in in-hospital cardiopulmonary arrest and differences in outcomes based on hospital characteristics.",2017 Aug 31,"['Park, Yeonhee', 'Ahn, Jong-Joon', 'Kang, Byung Ju', 'Lee, Young Seok', 'Ha, Sang-Ook', 'Min, Jin-Soo', 'Cho, Woo-Hyun', 'Na, Se-Hee', 'Lee, Dong-Hyun', 'Park, Seung-Yong', 'Hong, Goo-Hyeon', 'Kim, Hyun-Jung', 'Shim, Sangwoo', 'Kim, Jung-Hyun', 'Lee, Seok-Jeong', 'Park, So-Young', 'Moon, Jae Young']",Korean J Crit Care Med,,,False
8fefe8e70632ffdfd96f701facc6f2dcce16167a,PMC,Feline coronavirus-associated myocarditis in a domestic longhair cat,http://dx.doi.org/10.1177/2055116919879256,PMC6787879,31636915,CC BY-NC,"CASE SUMMARY: A 9-month-old entire male domestic longhair indoor cat presented with a 3-week history of fluctuating fever, weight loss and small intestine diarrhoea, which was unresponsive to antibiotics and supportive treatment. Abdominal ultrasound revealed severe jejunal and ileocolic junction intestinal wall thickening with loss of layering. An enterectomy was performed and histopathology revealed severe pyogranulomatous enteritis with vasculitits, compatible with the diagnosis of feline infectious peritonitis (FIP). Four days after surgery, the cat re-presented with anorexia and acute onset of expiratory dyspnoea. Echocardiography showed left ventricular hypertrophy and bilateral atrial enlargement. Congestive heart failure caused by hypertrophic cardiomyopathy was suspected and treatment with furosemide was started, which led to amelioration of the clinical signs. The following day, four-limb ataxia, hypermetria and bilateral uveitis were evident. Given the persistent anorexia and worsening of the clinical signs, the cat was humanely euthanized and a post-mortem examination was performed. Necropsy revealed multifocal pyogranulomatous lesions involving multiple organs (adrenal glands, kidneys, lungs, brain, myocardium, lymph nodes, liver), compatible with the diagnosis of FIP. Immunohistochemistry performed on the myocardium revealed feline coronavirus-positive macrophages associated with pyogranulomatous lesions, justifying a diagnosis of feline coronavirus-associated myocarditis. RELEVANCE AND NOVEL INFORMATION: To the authors’ knowledge, the case described here represents the first published report of feline coronavirus-associated myocarditis. This should be considered as a possible differential diagnosis in cats presenting with cardiac-related signs and other clinical signs compatible with FIP.",2019 Oct 10,"['Ernandes, Maria A', 'Cantoni, Anna M', 'Armando, Federico', 'Corradi, Attilio', 'Ressel, Lorenzo', 'Tamborini, Alice']",JFMS Open Rep,,,True
7b3a1e17837723ff83422617fef30925bab713a4,PMC,siRNAs Derived from Cymbidium Mosaic Virus and Odontoglossum Ringspot Virus Down-modulated the Expression Levels of Endogenous Genes in Phalaenopsis equestris,http://dx.doi.org/10.5423/PPJ.OA.03.2019.0055,PMC6788414,31632225,CC BY-NC,"Interplay between Cymbidium mosaic virus (CymMV)/Odontoglossum ringspot virus (ORSV) and its host plant Phalaenopsis equestris remain largely unknown, which led to deficiency of effective measures to control disease of P. equestris caused by infecting viruses. In this study, for the first time, we characterized viral small interfering RNAs (vsiRNAs) profiles in P. equestris co-infected with CymMV and ORSV through small RNA sequencing technology. CymMV and ORSV small interfering RNAs (siRNAs) demonstrated several general and specific/new characteristics. vsiRNAs, with A/U bias at the first nucleotide, were predominantly 21-nt long and they were derived predominantly (90%) from viral positive-strand RNA. 21-nt siRNA duplexes with 0-nt overhangs were the most abundant 21-nt duplexes, followed by 2-nt overhangs and then 1-nt overhangs 21-nt duplexes in infected P. equestris. Continuous but heterogeneous distribution and secondary structures prediction implied that vsiRNAs originate predominantly by direct Dicer-like enzymes cleavage of imperfect duplexes in the most folded regions of the positive strand of both viruses RNA molecular. Furthermore, we totally predicted 54 target genes by vsiRNAs with psRNATarget server, including disease/stress response–related genes, RNA interference core components, cytoskeleton-related genes, photosynthesis or energy supply related genes. Gene Ontology classification showed that a majority of the predicted targets were related to cellular components and cellular processes and performed a certain function. All target genes were down-regulated with different degree by vsiRNAs as shown by real-time reverse transcription polymerase chain reaction. Taken together, CymMV and ORSV siRNAs played important roles in interplay with P. equestris by down modulating the expression levels of endogenous genes in host plant.",2019 Oct 1,"['Lan, Han-hong', 'Wang, Cui-mei', 'Chen, Shuang-shuang', 'Zheng, Jian-ying']",Plant Pathol J,,,True
a9c5cb751437d911eeaacaf497c121b53fbc7f7a,PMC,siRNAs Derived from Cymbidium Mosaic Virus and Odontoglossum Ringspot Virus Down-modulated the Expression Levels of Endogenous Genes in Phalaenopsis equestris,http://dx.doi.org/10.5423/PPJ.OA.03.2019.0055,PMC6788414,31632225,CC BY-NC,"Interplay between Cymbidium mosaic virus (CymMV)/Odontoglossum ringspot virus (ORSV) and its host plant Phalaenopsis equestris remain largely unknown, which led to deficiency of effective measures to control disease of P. equestris caused by infecting viruses. In this study, for the first time, we characterized viral small interfering RNAs (vsiRNAs) profiles in P. equestris co-infected with CymMV and ORSV through small RNA sequencing technology. CymMV and ORSV small interfering RNAs (siRNAs) demonstrated several general and specific/new characteristics. vsiRNAs, with A/U bias at the first nucleotide, were predominantly 21-nt long and they were derived predominantly (90%) from viral positive-strand RNA. 21-nt siRNA duplexes with 0-nt overhangs were the most abundant 21-nt duplexes, followed by 2-nt overhangs and then 1-nt overhangs 21-nt duplexes in infected P. equestris. Continuous but heterogeneous distribution and secondary structures prediction implied that vsiRNAs originate predominantly by direct Dicer-like enzymes cleavage of imperfect duplexes in the most folded regions of the positive strand of both viruses RNA molecular. Furthermore, we totally predicted 54 target genes by vsiRNAs with psRNATarget server, including disease/stress response–related genes, RNA interference core components, cytoskeleton-related genes, photosynthesis or energy supply related genes. Gene Ontology classification showed that a majority of the predicted targets were related to cellular components and cellular processes and performed a certain function. All target genes were down-regulated with different degree by vsiRNAs as shown by real-time reverse transcription polymerase chain reaction. Taken together, CymMV and ORSV siRNAs played important roles in interplay with P. equestris by down modulating the expression levels of endogenous genes in host plant.",2019 Oct 1,"['Lan, Han-hong', 'Wang, Cui-mei', 'Chen, Shuang-shuang', 'Zheng, Jian-ying']",Plant Pathol J,,,False
17fd86bef40a55871ecfc83dc845f3a988bf4aaa,PMC,Structural and functional analyses reveal promiscuous and species specific use of ephrin receptors by Cedar virus,http://dx.doi.org/10.1073/pnas.1911773116,PMC6789926,31548390,CC BY-NC-ND,"Cedar virus (CedV) is a bat-borne henipavirus related to Nipah virus (NiV) and Hendra virus (HeV), zoonotic agents of fatal human disease. CedV receptor-binding protein (G) shares only ∼30% sequence identity with those of NiV and HeV, although they can all use ephrin-B2 as an entry receptor. We demonstrate that CedV also enters cells through additional B- and A-class ephrins (ephrin-B1, ephrin-A2, and ephrin-A5) and report the crystal structure of the CedV G ectodomain alone and in complex with ephrin-B1 or ephrin-B2. The CedV G receptor-binding site is structurally distinct from other henipaviruses, underlying its capability to accommodate additional ephrin receptors. We also show that CedV can enter cells through mouse ephrin-A1 but not human ephrin-A1, which differ by 1 residue in the key contact region. This is evidence of species specific ephrin receptor usage by a henipavirus, and implicates additional ephrin receptors in potential zoonotic transmission.",2019 Oct 8,"['Laing, Eric D.', 'Navaratnarajah, Chanakha K.', 'Cheliout Da Silva, Sofia', 'Petzing, Stephanie R.', 'Xu, Yan', 'Sterling, Spencer L.', 'Marsh, Glenn A.', 'Wang, Lin-Fa', 'Amaya, Moushimi', 'Nikolov, Dimitar B.', 'Cattaneo, Roberto', 'Broder, Christopher C.', 'Xu, Kai']",Proc Natl Acad Sci U S A,,,True
ca3d3e317e5c694091583d23c1cbcd0b68c88d27,PMC,Structural and functional analyses reveal promiscuous and species specific use of ephrin receptors by Cedar virus,http://dx.doi.org/10.1073/pnas.1911773116,PMC6789926,31548390,CC BY-NC-ND,"Cedar virus (CedV) is a bat-borne henipavirus related to Nipah virus (NiV) and Hendra virus (HeV), zoonotic agents of fatal human disease. CedV receptor-binding protein (G) shares only ∼30% sequence identity with those of NiV and HeV, although they can all use ephrin-B2 as an entry receptor. We demonstrate that CedV also enters cells through additional B- and A-class ephrins (ephrin-B1, ephrin-A2, and ephrin-A5) and report the crystal structure of the CedV G ectodomain alone and in complex with ephrin-B1 or ephrin-B2. The CedV G receptor-binding site is structurally distinct from other henipaviruses, underlying its capability to accommodate additional ephrin receptors. We also show that CedV can enter cells through mouse ephrin-A1 but not human ephrin-A1, which differ by 1 residue in the key contact region. This is evidence of species specific ephrin receptor usage by a henipavirus, and implicates additional ephrin receptors in potential zoonotic transmission.",2019 Oct 8,"['Laing, Eric D.', 'Navaratnarajah, Chanakha K.', 'Cheliout Da Silva, Sofia', 'Petzing, Stephanie R.', 'Xu, Yan', 'Sterling, Spencer L.', 'Marsh, Glenn A.', 'Wang, Lin-Fa', 'Amaya, Moushimi', 'Nikolov, Dimitar B.', 'Cattaneo, Roberto', 'Broder, Christopher C.', 'Xu, Kai']",Proc Natl Acad Sci U S A,,,True
eb828bb9f9c3a58b135f382517a9ebbe65fa6fc6,PMC,Point‐of‐care testing in primary care: A systematic review on implementation aspects addressed in test evaluations,http://dx.doi.org/10.1111/ijcp.13392,PMC6790572,31313873,CC BY-NC,"OBJECTIVES: There are numerous point‐of‐care tests (POCTs) available on the market, but many of these are not used. This study reviewed literature pertaining to the evaluation/usage of POCTs in primary care, to investigate whether outcomes being reported reflect aspects previously demonstrated to be important for general practitioners (GPs) in the decision to implement a POCT in practice. METHODS: Scopus and Medline were searched to identify studies that evaluated a POCT in primary care. We identified abstracts and full‐texts consisting of applied studies (eg trials, simulations, observational studies) and qualitative studies (eg interviews, surveys). Data were extracted from the included studies, such as the type of study, the extent to which manufacturers were involved in the study, and the biomarker/assay measured by the test(s). Studies were evaluated to summarise the extent to which they reported on, amongst others, clinical utility, user‐friendliness, turnaround‐time and technical performance (aspects previously identified as important). RESULTS: The initial search resulted in 1398 publications, of which 125 met the inclusion criteria. From these studies, 83 POCTs across several disease areas (including cardiovascular disease, venous thromboembolism and respiratory‐tract‐infections) were identified. There was an inconsistency between what is reported in the studies and what GPs consider important. GPs perceive clinical utility as the most important aspect, yet this was rarely included explicitly in test evaluations in the literature, with only 8% of evaluations incorporating it in their analysis/discussion. CONCLUSIONS: This review showed that, despite the growing market and development of new POCTs, studies evaluating such tests fail to report on aspects that GPs find important. To ensure that an evaluation of a POCT is useful to primary care clinicians, future evaluations should not only focus on the technical performance aspects of a test, but also report on the aspects relating to the clinical utility and risks.",2019 Oct 19,"['Lingervelder, Deon', 'Koffijberg, Hendrik', 'Kusters, Ron', 'IJzerman, Maarten J.']",Int J Clin Pract,,,True
75251cc3d312b0d2c63117458c68dba563715155,PMC,Prevention of respiratory outbreaks in the rehabilitation setting,http://dx.doi.org/10.1136/bmjoq-2019-000663,PMC6797241,31673641,CC BY-NC,"BACKGROUND: Respiratory viral (RV) outbreaks in rehabilitation facilities can jeopardise patient safety, interfere with patient rehabilitation goals and cause unit closures that impede patient flow in referring facilities. PROBLEM: Despite education about infection prevention practices, frequent RV outbreaks were declared each year at our rehabilitation facility. METHODS: Before and after study design. The primary outcome was the number of bed closure days due to outbreak per overall bed days. Process measures included delays in initiation of transmission-based precautions, RV testing and reporting of staff to occupational health and safety (OHS). Balancing measures included the number of isolation days and staff missed work hours. INTERVENTIONS: Based on comprehensive analysis of prior outbreaks, the following changes were implemented: (1) clear criteria for initiation of transmission-based precautions, (2) communication to visitors to avoid visitation if infectious symptoms were present, (3) exemption of staff absences if documented due to infectious illness, (4) development of an electronic programme providing guidance to staff about whether they should be excluded from work due to infectious illness. RESULTS: The number of bed closure days due to outbreak per overall bed days dropped from 2.8% to 0.5% during the intervention season and sustained at 0.6% during the postintervention season (p<0.001). There were fewer delays in initiation of droplet and contact precautions (28.8% to 15.5%, p=0.005) and collection of RV testing (42.9% to 20.3%, p<0.001), better reporting to OHS (9 vs 28.8 reports per 100 employees; p<0.001) and fewer isolation days (7.8% vs 7.3%; p=0.02) without a significant increase in missed work hours per 100 hours worked (4.0 vs 3.9; p=0.12). CONCLUSION: This Quality Improvement study highlights the process changes that can prevent respiratory outbreaks in the rehabilitation setting.",2019 Oct 9,"['Corpus, Carla', 'Williams, Victoria', 'Salt, Natasha', 'Agnihotri, Tanya', 'Morgan, Wendy', 'Robinson, Lawrence', 'Maze Dit Mieusement, Lorraine', 'Cobbam, Sonja', 'Leis, Jerome A']",BMJ Open Qual,,,True
e6cbbae9adbaf4928b36dd49c39147002aeb8973,PMC,Prevention of respiratory outbreaks in the rehabilitation setting,http://dx.doi.org/10.1136/bmjoq-2019-000663,PMC6797241,31673641,CC BY-NC,"BACKGROUND: Respiratory viral (RV) outbreaks in rehabilitation facilities can jeopardise patient safety, interfere with patient rehabilitation goals and cause unit closures that impede patient flow in referring facilities. PROBLEM: Despite education about infection prevention practices, frequent RV outbreaks were declared each year at our rehabilitation facility. METHODS: Before and after study design. The primary outcome was the number of bed closure days due to outbreak per overall bed days. Process measures included delays in initiation of transmission-based precautions, RV testing and reporting of staff to occupational health and safety (OHS). Balancing measures included the number of isolation days and staff missed work hours. INTERVENTIONS: Based on comprehensive analysis of prior outbreaks, the following changes were implemented: (1) clear criteria for initiation of transmission-based precautions, (2) communication to visitors to avoid visitation if infectious symptoms were present, (3) exemption of staff absences if documented due to infectious illness, (4) development of an electronic programme providing guidance to staff about whether they should be excluded from work due to infectious illness. RESULTS: The number of bed closure days due to outbreak per overall bed days dropped from 2.8% to 0.5% during the intervention season and sustained at 0.6% during the postintervention season (p<0.001). There were fewer delays in initiation of droplet and contact precautions (28.8% to 15.5%, p=0.005) and collection of RV testing (42.9% to 20.3%, p<0.001), better reporting to OHS (9 vs 28.8 reports per 100 employees; p<0.001) and fewer isolation days (7.8% vs 7.3%; p=0.02) without a significant increase in missed work hours per 100 hours worked (4.0 vs 3.9; p=0.12). CONCLUSION: This Quality Improvement study highlights the process changes that can prevent respiratory outbreaks in the rehabilitation setting.",2019 Oct 9,"['Corpus, Carla', 'Williams, Victoria', 'Salt, Natasha', 'Agnihotri, Tanya', 'Morgan, Wendy', 'Robinson, Lawrence', 'Maze Dit Mieusement, Lorraine', 'Cobbam, Sonja', 'Leis, Jerome A']",BMJ Open Qual,,,False
5b2945b68e31dfe32f721791a52b95f09b6a31bc,PMC,Vaccines for emerging pathogens: prospects for licensure,http://dx.doi.org/10.1111/cei.13284,PMC6797873,30972733,CC BY-NC,"Globally, there are a number of emerging pathogens. For most, there are no licensed vaccines available for human use, although there is ongoing research and development. However, given the extensive and increasing list of emerging pathogens and the investment required to bring vaccines into clinical use, the task is huge. Overlaid on this task is the risk of anti‐microbial resistance (AMR) acquisition by micro‐organisms which can endow a relatively harmless organism with pathogenic potential. Furthermore, climate change also introduces a challenge by causing some of the insect vectors and environmental conditions prevalent in tropical regions to begin to spread out from these traditional areas, thus increasing the risk of migration of zoonotic disease. Vaccination provides a defence against these emerging pathogens. However, vaccines for pathogens which cause severe, but occasional, disease outbreaks in endemic pockets have suffered from a lack of commercial incentive for development to a clinical standard, encompassing Phase III clinical trials for efficacy. An alternative is to develop such vaccines to request US Emergency Use Authorization (EUA), or equivalent status in the United States, Canada and the European Union, making use of a considerable number of regulatory mechanisms that are available prior to licensing. This review covers the status of vaccine development for some of the emerging pathogens, the hurdles that need to be overcome to achieve EUA or an equivalent regional or national status and how these considerations may impact vaccine development for the future, such that a more comprehensive stockpile of promising vaccines can be achieved.",2019 Nov 11,"['Williamson, E. D.', 'Westlake, G. E.']",Clin Exp Immunol,,,True
03e8628eb61ff4c66a17673745a7b9c33aece853,PMC,The burden of severe cases of Influenza disease: the Friuli Venezia Giulia Region experience,http://dx.doi.org/10.15167/2421-4248/jpmh2019.60.3.1314,PMC6797893,31650049,CC BY-NC,"INTRODUCTION: Influenza is a matter of serious concern for clinicians, in both outpatient and in-hospital settings. Worldwide, the 2017-18 epidemic proved to be the most severe since 2003-04. We report a real-world experience regarding the management of patients with influenza admitted to a large teaching hospital in the Friuli Venezia Giulia region during the 2017-2018 influenza season. We also provide a practical guide for the management of hospitalized influenza patients. METHODS: A retrospective observational analysis was conducted among all influenza patients requiring admission to our center during the 2017-18 season. RESULTS: Overall, 29 patients were admitted to the University Hospital of Udine during the 2017-18 season with a diagnosis of influenza. B virus was responsible for the majority of cases. More than 65.5% of the subjects presented with a complication. We estimated that 41.4% of the patients admitted were affected by a “severe form”. All these cases required admission to the Intensive Care Unit, with 27.6% and 10.3% needing Orotracheal Intubation and Extracorporeal Membrane Oxygenation, respectively. The fatality rate was 24.1%. Notably, only 9 subjects in our cohort had been vaccinated. Based on the experience acquired during the past season, we propose a practical guide to the management of influenza cases in everyday hospital practice. CONCLUSION: The cornerstones of the management of all hospitalized influenza patients are the rapid identification and treatment of severe forms. Timely and strict adherence to contact and respiratory precautions are also fundamental to reducing the risk of intra-hospital outbreaks. Despite improvements in antiviral therapies and supportive measures, influenza-related morbidity and mortality remain high. In our opinion, a universal vaccination program is the only safe and effective method of filling the gap.",2019 Sep 30,"['BASSETTI, M.', 'PEGHIN, M.', 'GALLO, T.', 'PIPAN, C.', 'D’AGARO, P.', 'SARTOR, A.', 'BOVE, T.', 'COCCONI, R.', 'GRAZIANO, E.', 'CASTALDO, N.']",J Prev Med Hyg,,,True
db71883643ea4dbc79a8f3e5248811d9c3385c3e,PMC,Static DNA Nanostructures For Cancer Theranostics: Recent Progress In Design And Applications,http://dx.doi.org/10.2147/NSA.S227193,PMC6800557,31686793,CC BY-NC,"Among the various nano/biomaterials used in cancer treatment, the beauty and benefits of DNA nanocomposites are outstanding. The specificity and programmability of the base pairing of DNA strands, together with their ability to conjugate with different types of functionalities have realized unsurpassed potential for the production of two- and three-dimensional nano-sized structures in any shape, size, surface chemistry and functionality. This review aims to provide an insight into the diversity of static DNA nanodevices, including DNA origami, DNA polyhedra, DNA origami arrays and bioreactors, DNA nanoswitch, DNA nanoflower, hydrogel and dendrimer as young but promising platforms for cancer theranostics. The utility and potential of the individual formats in biomedical science and especially in cancer therapy will be discussed.",2019 Oct 15,"['Jahanban-Esfahlan, Rana', 'Seidi, Khaled', 'Jahanban-Esfahlan, Ali', 'Jaymand, Mehdi', 'Alizadeh, Effat', 'Majdi, Hasan', 'Najjar, Reza', 'Javaheri, Tahereh', 'Zare, Peyman']",Nanotechnol Sci Appl,,,True
576176e6d8ee4629ca0228dff8a6ceb74ff7edb2,PMC,2002. BioFire® Filmarray® Pneumonia Panel: A Powerful Rapid Diagnostic Test for Antimicrobial Stewardship,http://dx.doi.org/10.1093/ofid/ofz360.1682,PMC6808661,,CC BY-NC-ND,"BACKGROUND: BioFire® Filmarray® Pneumonia Panel (BFPP) is a multiplex PCR panel that identifies 33 common bacterial and viral pathogens seen in community- and hospital-acquired pneumonias. It rapidly identifies these pathogens in addition to 7 antibiotic resistance genes on sputum and bronchioalveolar lavage samples in 1 hour. As one of the test centers for this panel, our institution utilized this panel for clinical and laboratory use. We reviewed the impact of BFPP on antimicrobial stewardship, particularly its role in early discontinuation of empiric antibiotics and prompt initiation of optimized targeted therapy. METHODS: We retrospectively reviewed all cases by which BFPP was ordered. We reviewed medical records of each case to identify the results of the panel, culture data, antibiotics used, and subsequent clinical intervention. RESULTS: 43 tests were ordered in total. 17 were for clinical use by an infectious disease specialist and 26 were randomly obtained by the microbiology lab. All 17 clinical cases were intervened upon with the following interventions: discontinuation of anti-pseudomonal antibiotics (8 cases), discontinuation of anti-MRSA antibiotics (5 cases), discontinuation of azithromycin (4 cases), discontinuation of carbapenem (1 case), prevention of inappropriate antibiotic escalation or initiation of inappropriate antibiotics (2 cases), and early IV to PO transition (3 cases). Of the random 26 samples ordered by lab, 13 had opportunities for antibiotic de-escalation if a physician were notified of the results. Viruses were identified in 15 samples with coronavirus being the most common. Virus was the sole pathogen in 9 of the 15 samples. Bacterial pathogens were identified in 20 samples that were reported as normal flora by conventional culture; none of these cases led to or potentially could have led to antibiotic escalation as the sole intervention. CONCLUSION: Clinical use of BFPP had 100% intervention rate with all interventions leading to de-escalation of antibiotics or prevention of inappropriate antibiotics use. Though over-identification of colonizers is a potential limitation, BFPP is a powerful tool for antibiotic stewardship that results in rapid interventions to achieve optimal targeted therapy. DISCLOSURES: All authors: No reported disclosures.",2019 Oct 23,"['Furukawa, Daisuke', 'Kim, Brian', 'Jeng, Arthur']",Open Forum Infect Dis,,,False
0afbc3efd63bd1b65615182d879c1209cbc4dcc0,PMC,1756. Role of Human bocavirus Respiratory Tract Infection in Hematopoietic Cell Transplant Recipients,http://dx.doi.org/10.1093/ofid/ofz360.1619,PMC6808672,,CC BY-NC-ND,"BACKGROUND: Limited data exist regarding the impact of human bocavirus (BoV) in hematopoietic cell transplant (HCT) recipients. We examined incidence and disease spectrum of BoV respiratory tract infection (RTI) in HCT recipients. METHODS: In a longitudinal surveillance study of viral RTIs among allogeneic HCT recipients, pre-HCT and weekly post-HCT nasal washes and symptom surveys were collected through day 100, then every 3 months, and whenever respiratory symptoms occurred through 1-year post-HCT. Samples were tested by multiplex semi-quantitative PCR for RSV, parainfluenza virus 1–4, influenza A/B, adenovirus, human metapneumovirus, rhinovirus, coronavirus, and BoV. Plasma samples from BoV+ subjects were analyzed by PCR. In addition, we conducted a retrospective review of HCT recipients with BoV detected in bronchoalveolar lavage or lung biopsy. RESULTS: Among 469 patients in the prospective cohort, 21 distinct BoV RTIs (3 pre-HCT and 18 post-HCT) were observed by 1-year post-HCT in 19 patients (median 42 years old, range 0–67) without apparent seasonality. BoV was more frequently detected in the latter half of the first 100 days post-HCT (Figure 1). The frequencies of respiratory symptoms in patients with BoV detected did not appear to be higher than those without any virus detected, with the exception of watery eyes (P < 0.01) (Figure 2). Univariable models among patients with BoV RTI post-HCT showed higher peak viral load in nasal samples (P = 0.04) and presence of respiratory copathogens (P = 0.03) were associated with presence of respiratory symptoms; however, BoV detection in plasma was not (P = 0.8). Retrospective review identified 6 allogeneic HCT recipients (range 1–64 years old) with BoV detected in lower respiratory tract specimens [incidence rate of 0.4% (9/2,385) per sample tested]. Although all 6 cases presented with hypoxemia, 4 had significant respiratory copathogens or concomitant conditions that contributed to respiratory compromise. No death was attributed mainly to BoV lower RTI. CONCLUSION: BoV is infrequently detected in respiratory tract in HCT recipients. Our studies did not demonstrate convincing evidence that BoV is a significant pathogen in either upper or lower respiratory tracts. Watery eyes were associated with BoV detection. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.",2019 Oct 23,"['Ogimi, Chikara', 'Martin, Emily T', 'Xie, Hu', 'Campbell, Angela P', 'Waghmare, Alpana', 'Kuypers, Jane', 'Jerome, Keith', 'Leisenring, Wendy', 'Englund, Janet A', 'Boeckh, Michael']",Open Forum Infect Dis,,,False
cde5da0e034fde8c82990e0880b93053f80400e9,PMC,1791. Novel Metabolomics Approach for the Diagnosis of Respiratory Viruses Directly from Nasopharyngeal Specimens,http://dx.doi.org/10.1093/ofid/ofz360.1654,PMC6809267,,CC BY-NC-ND,"BACKGROUND: Respiratory virus infections are important causes of morbidity and mortality among pediatric and adult patients. These viruses infect respiratory epithelial cells, where they may induce specific metabolite alterations. As a proof-of-concept, we investigate the novel use of liquid chromatography (LC) combined with quadrupole time-of-flight mass spectrometry (Q-TOF) for the study of host cell metabolite alterations to diagnose and differentiate respiratory viruses. METHODS: We studied nasopharyngeal swab samples positive for respiratory viruses by the eSensor Respiratory Viral Panel (GenMark Diagnostics, Carlsbad, CA). Banked, frozen samples (−80°C) stored in viral transport media were retrieved and thawed. Aliquots of 100 μL were centrifuged at 13.3 × g for 15 minutes, and the filtrate was analyzed by Agilent 6545 Quadrupole LC/Q-TOF (Agilent Technologies, Santa Clara, CA). Compounds were separated using a novel column arrangement based on hydrophobicity and charge using a quaternary solvent manager, followed by accurate mass analysis by LC/Q-TOF. Agilent Mass Profiler 3D principal component analysis was performed, and compound identification was completed using the METLIN metabolite database. RESULTS: A total of 235 specimens were tested by LC/Q-TOF, including 195 positive specimens [including adenovirus, coronavirus, influenza A H1N1 and H3N2, influenza B, human metapneumovirus, parainfluenza viruses 1, 2, 3, and 4, respiratory syncytial virus (RSV), and rhinovirus] as well as 40 negative clinical specimens. LC/Q-TOF primary component analysis (PCA) allowed preliminary identification of key metabolites that distinguished all virus-positive specimens compared with the negative group, and differentiated respiratory viruses from one another including between influenza A 2009 H1N1 and H3N2 subtypes (Figure 1). CONCLUSION: Preliminary data from our LC/Q-TOF analysis show that respiratory viruses exhibit different host cell metabolomic profiles that allow viral differentiation to the species level, and for influenza A virus, the subtype level. This metabolomic approach has substantial potential for diagnostic applications in infectious diseases directly from patient samples, and may be eventually adapted for point-of-care testing. [Image: see text] DISCLOSURES: All authors: No reported disclosures.",2019 Oct 23,"['Hogan, Catherine', 'Le, Anthony T', 'Mak, Justin', 'Kumar. Sahoo, Malaya', 'Cowan, Tina', 'Pinksy, Benjamin A']",Open Forum Infect Dis,,,False
00260429f4bddc57b04f025adb6c91c28cb4580b,PMC,2786. The Role of Respiratory Panel PCR in Decreasing Antibiotic Exposure in Patients Diagnosed With a Respiratory Viral Infection,http://dx.doi.org/10.1093/ofid/ofz360.2463,PMC6809478,,CC BY-NC-ND,"BACKGROUND: Respiratory viral infections (RVI) are becoming increasingly recognized as an important cause of pneumonia. There is limited data regarding the role of rapid PCR testing for RVI and its effect on antibiotic duration and length of stay (LOS). METHODS: We performed a single-center, retrospective chart review in adult patients who were admitted and underwent evaluation with the FilmArray Multiplex Respiratory Panel (RP) (Biomerieux™) using a random sample from July 1, 2016 through April 1, 2018. Patient clinical and virologic characteristics, LOS, antibiotic use, and duration of treatment were collected. A Student’s t-test was performed for all comparisons. RESULTS: We identified 540 patients who were admitted and underwent RP testing. The mean age was 57.1 years (range 19–99), 50.2% were immunocompromised, 23.8% were transplant recipients, 70.4% had respiratory symptoms, and 35.7% had an admitting diagnosis of pneumonia. 55.6% required supplemental O(2) and 24.6% had an ICU admission that required either noninvasive or mechanical ventilation. 22.6% (N = 122) of these patients were diagnosed with an RVI, of which 15 were co-infected with two or more respiratory viruses. There were 41 (34%) rhinovirus/enterovirus, 41 (34%) influenza (Types A/H1, A/H3, A/H1-2209, and B), 16 (13%) RSV, 15 (12%) coronavirus (Types NL63, OC43, 229E, and HKU1), 13 (11%) metapneumovirus, and 7 (5%) parainfluenza (Types 2, 3, and 4). 85.2% (104/122) of patients with an RVI received antibiotics. The mean LOS and antibiotic duration were 9.07 days and 7.31 days for patients with an RVI when compared with 11.5 days and 10.4 days for patients without an RVI (P = 0.098; P = 0.032), respectively. In patients with an RVI and negative bacterial cultures, the mean LOS was 8.4 days and mean antibiotic duration was 5.9 days when compared with 16.4 days and 15.5 days for all patients with positive bacterial cultures (P = 0.003; P < 0.0001), respectively. The mean time from available results of + RP to antibiotic discontinuation was 5.1 days in the setting of negative bacterial cultures. CONCLUSION: Although antibiotic exposure and time to discontinuation still remained significant in patients diagnosed with an RVI, there was a marked reduction in LOS and antibiotic duration in the subset of patients with an RVI and negative bacterial cultures. DISCLOSURES: All authors: No reported disclosures.",2019 Oct 23,"['Vostal, Alexander', 'Gonzalez, Michael Antonio', 'Darling, Nellie', 'Papastamelos, Christine', 'Natarajan, Madhuri', 'Kumar, Princy', 'Timpone, Joseph']",Open Forum Infect Dis,,,False
7896f68d228522d176850fc9845d57f1fd25ea5e,PMC,"2792. Association of Body Mass Index with Rates of Hospitalization in Patients with Respiratory Viral Infections—Puerto Rico, 2012–2018",http://dx.doi.org/10.1093/ofid/ofz360.2469,PMC6809817,,CC BY-NC-ND,"BACKGROUND: Obesity is a serious public health problem in Puerto Rico, where 31% of the population is obese. Multiple studies have suggested that adults with influenza who are underweight, overweight, or obese have increased risk of hospitalization compared with those of normal weight. We sought to determine whether risk of hospitalization among patients infected with influenza or other respiratory viruses differs by BMI among patients in Puerto Rico. METHODS: We analyzed data from patients enrolled in the Sentinel Enhanced Dengue Surveillance System (SEDSS), a prospective study of patients with acute febrile illness (AFI), from May 2012 to September 2018. We evaluated those older than 24 months, who had height, weight, and clinical disposition recorded, and tested positive by RT–PCR for infection with influenza A (n = 1253), influenza B (n = 844), adenovirus (n = 435), respiratory syncytial virus (n = 289), parainfluenza virus (n = 361), metapneumovirus (n = 247), or coronavirus (n = 15). BMI categories were determined using standard cutoffs in adults and BMI-for-age percentiles for children and adolescents. Risk of hospitalization by BMI category was calculated using multivariate Poisson regression. RESULTS: Among the 3,388 patients included, 675 (20%) were overweight, 926 (27%) were obese, 405 (12%) were underweight, and 1382 (41%) were normal weight. Median age was 13.4 (range: 2–100 years), and 50% were male. Risk of hospitalization was not significantly different in children and adult patients infected with a respiratory virus who were overweight relative to those that had normal BMI; however, once hospitalized, obese individuals of any age had a mean length of hospital stay 1.7 days longer than normal weight persons (95% CI: 0.27–3.17 days). Among adult patients, underweight patients were nearly 3 times more likely to be hospitalized compared with normal weight patients (relative risk 2.8, 95% CI: 1.4–5.9). Underweight children were not at increased risk of hospitalization. CONCLUSION: Among patients infected with a respiratory virus, risk of hospitalization was higher among underweight adult patients, and obese patients had a longer mean length of stay once hospitalized. Body mass index should be considered when evaluating risk and managing these patients. DISCLOSURES: All authors: No reported disclosures.",2019 Oct 23,"['Tobolowsky, Farrell A', 'Zambrano, Laura', 'Sharp, Tyler', 'Beckham, John David', 'Alvarado, Luisa', 'Paz-Bailey, Gabriela']",Open Forum Infect Dis,,,False
a06bf20070537f1165c21f428aac86070f850ab6,PMC,1675. Implementation of Electronic Travel History Screening at an Urban Medical Center,http://dx.doi.org/10.1093/ofid/ofz360.1539,PMC6809912,,CC BY-NC-ND,"BACKGROUND: Middle East Respiratory Syndrome (MERS), caused by a novel coronavirus, can lead to severe respiratory failure and death. CDC recommends screening patients who traveled to endemic countries for fever, respiratory symptoms, and exposure to MERS-positive contacts and healthcare facilities. UCLA is a large, academic, medical center located in a diverse city with frequent international travel. We implemented a travel screening (TS) questionnaire in our electronic medical record (EMR) (Figure 1) to identify high-risk patients in order to implement early isolation practices and testing. This study describes the use and performance of our TS for identifying suspect MERS cases. METHODS: An EMR-based tool prompts nurses to ask patients at triage or admission whether they have traveled out of the country in the past 30 days (Figure 1). If patients answer affirmatively, the EMR prompts nurses to inquire about travel to specific high-risk countries and to review symptoms and exposure risks. Upon notification of a potential MERS case, the EID physician on-call reviews the TS, clinical history, epidemiologic risks, and makes a determination whether further evaluation and/or isolation for suspect MERS is necessary. We reviewed travel history, demographics, and symptoms of patients who triggered a positive TS from April 2017 to September 2018. RESULTS: The ED completed 115,815 distinct TS on 81,197 individuals during this time period. The median time from ED arrival to TS completion was 6.4 minutes. 308 ED encounters triggered a positive TS; an additional 257 encounters in other units triggered a positive TS, resulting in 565 positive TS (Table 1). 122 (22%) expressed ≥1 MERS symptom and 29 (24%) expressed both fever and respiratory symptoms. Of these symptomatic patients, 0 had a history of contact with a MERS case; 3 had a history of contact with a healthcare facility while traveling; and 4 had a history of contact with camels. No patients were diagnosed with MERS (Table 2). CONCLUSION: A history of travel to the MERS endemic countries is relatively common at a large urban hospital. Routine electronic screening of patients is an efficient way to identify high-risk travelers. This EMR tool could be modified for other emerging pathogens, such as measles or Ebola, to identify high-risk patients. [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.",2019 Oct 23,"['de St. Maurice, Annabelle M', 'Martinez, Sandra', 'Sweeney, Sarah', 'Genta, Elizabeth', 'Walton, Shaunte', 'Rubin, Zachary A', 'Uslan, Daniel']",Open Forum Infect Dis,,,False
81ae2aa4696d328286059bce6eafe50ee65ab832,PMC,2324. Respiratory Viral Coinfection in a Birth Cohort of Infants in Rural Nepal,http://dx.doi.org/10.1093/ofid/ofz360.2002,PMC6810005,,CC BY-NC-ND,"BACKGROUND: Acute respiratory illnesses are a leading cause of global morbidity and mortality in children. Coinfection with multiple respiratory viruses is common. Although the effects of each virus have been studied individually, the effects of coinfection on disease severity or healthcare seeking are less well-understood. METHODS: A secondary analysis was performed of a maternal influenza vaccine trial conducted between 2011 and 2014 in rural southern Nepal. Prospective weekly active household-based surveillance of infants was conducted from birth to 180 days of age. Mid-nasal swabs were collected and tested for respiratory syncytial virus (RSV), rhinovirus, influenza, human metapneumovirus (HMPV), coronavirus, parainfluenza (HPIV), and bocavirus by RT–PCR. Coinfection was defined as the presence of two or more respiratory viruses simultaneously detected as part of the same illness episode. Maternal vaccination status, infant age, prematurity, and number of children under 5 in the household were adjusted for with multivariate logistic regression. RESULTS: Of 1,730 infants with a respiratory illness, 327 (19%) had at least two respiratory viruses detected on their primary illness episode. Coinfection status did not differ by maternal vaccination status, infant age, premature birth, and number of children under 5 in the household. Of 113 infants with influenza, 23 (20%) had coinfection. Of 214 infants with RSV, 87 (41%) had coinfection. Overall, infants with coinfection had increased occurrence of fever lasting 4 or more days overall (OR 1.4, 95% CI: 1.1, 2.0), and in the subset of infants with influenza (OR 5.8, 95% CI: 1.8, 18.7). Coinfection was not associated with seeking further care (OR 1.1, 95% CI: 0.8, 1.5) or pneumonia (OR 1.2, 95% CI: 1.0, 1.6). CONCLUSION: A high proportion of infants experiencing their first respiratory illness had multiple viruses detected. Coinfection with influenza was associated with longer duration of fever compared with children with influenza alone, but was not associated with increased illness severity by other measures. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.",2019 Oct 23,"['Emanuels, Anne', 'Newman, Kira L', 'Hawes, Stephen E', 'Martin, Emily T', 'Englund, Janet A', 'Tielsch, James', 'Kuypers, Jane', 'Katz, Joanne', 'Khatry, Subarna', 'LeClerq, Steven', 'Chu, Helen Y']",Open Forum Infect Dis,,,False
96237ed99dde8c2046b3c645814423f7a7e87c54,PMC,2626. Rhinovirus in Children Presenting to the Emergency Department: Role of Viral Load in Disease Severity and Co-Infections,http://dx.doi.org/10.1093/ofid/ofz360.2304,PMC6810026,,CC BY-NC-ND,"BACKGROUND: Rhinovirus (RV) quantitation by reverse transcription-quantitative PCR is limited by variable amplification efficiency across genotypes. We used a precise viral quantitation method, reverse transcription-digital PCR (RT-dPCR), to characterize the role of viral load in clinical outcomes and in viral co-infections in children presenting to a tertiary hospital emergency department (ED). METHODS: Children < 18 years with respiratory symptoms for ≤ 14 days were enrolled from December 1, 2016 to December 31, 2018. Participants had nasal and throat specimens obtained and multiplex PCR testing with a commercial assay (FilmArray; bioMerieux). RV positive samples were quantified using RT-dPCR. Samples with sufficient viral load were sequenced at a 543 bp fragment of the RV VP4/VP2 region. RV species were assigned by comparison to RV sequences in GenBank using BLAST. Clinical data were collected into REDCap. T-tests were used to compare mean viral loads between groups. RESULTS: Of 1703 children enrolled in the ED, 697 were RV/enterovirus positive by FilmArray [median age 18 months (interquartile range 9–39 months)]. Of 590 subjects with viral load available, 276 (47%) were admitted to the hospital. Among RV mono-infections (N = 434), mean viral load did not differ between subjects admitted vs. discharged from the ED (7.03 log copies/mL for both, P = 0.97). Among admitted subjects with RV mono-infection, viral load also did not differ between subjects requiring supplemental oxygen vs. not (7.01 vs. 7.10 log copies/mL, P = 0.6). Subjects with viral co-infections had lower mean RV viral loads (6.31 log copies/mL) compared with those with RV only (7.03 log copies/mL; P < 0.001) (figure). Significantly different RV viral loads were seen with co-infections with respiratory syncytial virus (RSV), metapneumovirus (MPV) and parainfluenza (PIV), but not with influenza, adenovirus or coronavirus. In 525 sequenced samples (46% RV-A, 4% RV-B, 50% RV-C), viral load did not vary between RV viral species (P = 0.09). CONCLUSION: Precise viral quantitation demonstrates children co-infected with RV and RSV, MPV or PIV have lower nasal viral loads than those with RV alone. Among RV mono-infections, RV viral load was not associated with admission or need for supplemental oxygen. [Image: see text] DISCLOSURES: All authors: No reported disclosures.",2019 Oct 23,"['Waghmare, Alpana', 'Strelitz, Bonnie', 'Lacombe, Kirsten', 'Perchetti, Garrett', 'Nalla, Arun', 'Rha, Brian', 'Midgley, Claire', 'Lively, Joana Y', 'Klein, Eileen J', 'Kuypers, Jane', 'Englund, Janet A']",Open Forum Infect Dis,,,False
bcc68fabbc7b37ab751c5981cdc4320a48ca8408,PMC,1642. Comparing Viral Respiratory Infections Between Children Who Do and Do Not Attend Child Care,http://dx.doi.org/10.1093/ofid/ofz360.1506,PMC6810424,,CC BY-NC-ND,"BACKGROUND: Out-of-home child care (CC) is a risk factor for viral acute respiratory infection (ARI) in young children. Little is known, however, about differences in frequencies of viral infection between CC children and those cared for exclusively at home. METHODS: Using surveillance data from the HIVE household cohort in southeast Michigan from 2014–2018 (4 seasons), we analyzed 1022 illness cases from 354 children aged 0–6 years. Age groups were dichotomized as infants (aged <2 years) and toddlers/preschoolers (aged 2–6 years). Households were prospectively enrolled and nasal respiratory swabs were collected from children upon report of acute illness symptoms. We used real-time RT–PCR to test for 18 respiratory viruses. RESULTS: We detected at least one virus in 855 illness cases (83% of all illnesses reported). Age at first illness onset in all four seasons was significantly younger among CC children than homecare children (P < 0.001) across all 4 years (average difference = 1.25 years). CC children <2 years had slightly lower odds of viral detection during illness (OR = 0.89, 95% CI [0.49, 1.61]) but higher odds at ages 2–6y (1.07 [0.65, 1.76]); neither was statistically significant. Neither CC nor homecare children were significantly more or less at risk for any particular pathogen—expect for rhinovirus in the <2-year group, where odds of rhinovirus infection were 58% lower (OR = 0.42) in CC children compared with homecare counterparts (95% CI, 0.21–0.83). Conversely, CC attendees under 3 more frequently had influenza, RSV, hMPV, parainfluenza, and coronavirus; however, none of these associations were significant. Odds of coinfection (> 1 virus detected) were higher among CC children, but not significant (OR = 1.4 [0.63, 2.96] and 1.2 [0.77, 1.88] in <2 year and 2–6 year age groups, respectively). Among all children <7 year, the mean number of pathogens detected was not different between CC and homecare individuals (1.20 vs. 1.23, P = 0.16). CONCLUSION: As expected, results indicated that CC attendees aged 0–6y experienced illness episodes earlier in life compared with homecare children. Our analysis also indicated that, compared with children cared for at home, CC children were less at risk for rhinovirus infection when young but could potentially be at higher risk for viruses of greater clinical concern. DISCLOSURES: All authors: No reported disclosures.",2019 Oct 23,"['DeJonge, Peter', 'Malosh, Ryan', 'Truscon, Rachel', 'Johnson, Emileigh', 'Foote, Sydney', 'Cheng, Bonnie', 'Tiseo, Katie E', 'Getz, Amy S', 'Segaloff, Hannah', 'Monto, Arnold', 'Martin, Emily T']",Open Forum Infect Dis,,,False
05d4815ef4cb7be7b98de47c136409d905696463,PMC,2448. Clinical Presentation and Outcomes of Long-Term Care Residents with Coronavirus Respiratory Infection: A Retrospective Cohort Study,http://dx.doi.org/10.1093/ofid/ofz360.2126,PMC6810513,,CC BY-NC-ND,"BACKGROUND: Human coronaviruses (CoVs) are a major cause of respiratory infection and institutional outbreaks, yet the epidemiology and clinical outcomes of these viruses is poorly described among the elderly residing in long-term care facilities (LTCFs). METHODS: We performed a retrospective cohort study of LTCF residents with positive nasopharyngeal or mid-turbinate swabs for CoVs (OC43, 229E, NL63 and HKU1) between January 2013 and December 2018. Demographic and clinical data were obtained from resident charts including clinical presentation, treatment, outcome, and transmission to other residents. Variables were compared using univariate analysis. RESULTS: 3268 residents met inclusion criteria (median age 93 years, 90% male) comprising 7.5% (246/3268) of all positive respiratory virus specimens detected during the study period. 97(39%) of cases were associated with a respiratory outbreak while 149(61%) were sporadic cases that did not result in transmission. OC43 (52%) was the most commonly identified CoV and was more commonly associated with outbreak cases (76% vs. 37%; P < 0.001). In total, 87% of all cases had two or more of runny nose/congestion, cough, sore throat/hoarse voice or fever. The most common symptoms among residents were cough (85%), runny nose/congestion (79%), and sore throat/hoarse voice (59%) and only 17% of residents had a measured temperature of ≥ 37.8C. Only 6% of residents received antibiotic treatment for suspected secondary bacterial pneumonia. The 30-day mortality rate was 3.7% with 67% of deaths attributable to the CoV infection. There was no statistically significant difference in symptoms, treatment or outcomes associated with outbreaks or seasonality. CONCLUSION: CoVs make up an important proportion of respiratory viral infections among LTCF residents and may result in frequent outbreaks. Most residents remain afebrile and have self-limited illness while only a small minority develop secondary bacterial pneumonia and death. Given these findings the benefits of control measures should be weighed against the impact on resident quality of life. DISCLOSURES: All authors: No reported disclosures.",2019 Oct 23,"['Williams, Victoria R', 'Pajak, Dariusz', 'Salt, Natasha', 'Leis, Jerome A']",Open Forum Infect Dis,,,False
d690af2217392d3b4686d86b6cb0434918f71f9b,PMC,Emerging infectious disease laboratory and diagnostic preparedness to accelerate vaccine development,http://dx.doi.org/10.1080/21645515.2019.1634992,PMC6816404,31268394,CC BY-NC-ND,"Rapid vaccine development in response to an outbreak of a new emerging infectious disease (EID) is a goal targeted by public health agencies worldwide. This goal becomes more complicated when there are no standardized sets of viral and immunological assays, no accepted and well-characterized samples, standards or reagents, and no approved diagnostic tests for the EID pathogen. The diagnosis of infections is of critical importance to public health, but also in vaccine development in order to track incident infections during clinical trials, to differentiate natural infection responses from those that are vaccine-related and, if called for by study design, to exclude subjects with prior exposure from vaccine efficacy trials. Here we review emerging infectious disease biological standards development, vaccine clinical assay development and trial execution with the recent experiences of MERS-CoV and Zika virus as examples. There is great need to establish, in advance, the standardized reagents, sample panels, controls, and assays to support the rapid advancement of vaccine development efforts in response to EID outbreaks.",2019 Jul 16,"Roberts, Christine C.",Hum Vaccin Immunother,,,True
d690e4df20380e92f907315e831f39116b1c460d,PMC,Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens,http://dx.doi.org/10.1080/21645515.2019.1649532,PMC6816421,31368826,CC BY-NC-ND,"The devastating Ebola virus (EBOV) outbreak in West Africa in 2013–2016 has flagged the need for the timely development of vaccines for high-threat pathogens. To be better prepared for new epidemics, the WHO has compiled a list of priority pathogens that are likely to cause future outbreaks and for which R&D efforts are, therefore, paramount (R&D Blueprint: https://www.who.int/blueprint/priority-diseases/en/). To this end, the detailed characterization of vaccine platforms is needed. The vesicular stomatitis virus (VSV) has been established as a robust vaccine vector backbone for infectious diseases for well over a decade. The recent clinical trials testing the vaccine candidate VSV-EBOV against EBOV disease now have added a substantial amount of clinical data and suggest VSV to be an ideal vaccine vector candidate for outbreak pathogens. In this review, we discuss insights gained from the clinical VSV-EBOV vaccine trials as well as from animal studies investigating vaccine candidates for Blueprint pathogens.",2019 Sep 5,"['Fathi, Anahita', 'Dahlke, Christine', 'Addo, Marylyn M.']",Hum Vaccin Immunother,,,True
5c1dd2b19bb6b3016ba2654f69905bf4ec65bd54,PMC,"“Running the Gauntlet”: Formidable challenges in advancing neglected tropical diseases vaccines from development through licensure, and a “Call to Action”",http://dx.doi.org/10.1080/21645515.2019.1629254,PMC6816440,31180271,CC BY-NC-ND,"Translational science for new biotechnologies (e.g. drugs, vaccines, devices, or diagnostics) depend on the development of a robust ‘business case’. This is driven by complex scientific, technical, logistical, financial and operational elements to determine the feasibility and probability of traversing the “valleys of death” leading to licensure. The potential results in terms of profitability and financial realization, called ‘product value proposition’ play a crucial role in establishing incentives for investment during and after development. With this review, our goal is to summarize the challenges in taking vaccines against neglected tropical diseases (NTDs) from development through licensure and provide a perspective that these vaccines can have measurable public health and economic profitability and market success. Understanding these processes and its challenges would open the opportunity to accelerate and advance these essential NTD vaccines through the last mile towards licensure and for the delivery to afflicted populations in low- and middle-income countries.",2019 Jul 10,"['Bottazzi, Maria Elena', 'Hotez, Peter J.']",Hum Vaccin Immunother,,,True
3dc1b1e197ec2bdd5ee03a588505a7a7c127c79d,PMC,"Common cold in Team Finland during 2018 Winter Olympic Games (PyeongChang): epidemiology, diagnosis including molecular point-of-care testing (POCT) and treatment",http://dx.doi.org/10.1136/bjsports-2018-100487,PMC6818521,31142472,CC BY-NC,"OBJECTIVES: The common cold is the main cause of medical time loss in elite sport. Rapid diagnosis has been a challenge that may be amenable to molecular point-of-care testing (POCT). METHODS: We performed a prospective observational study of the common cold in Team Finland during the 2018 Winter Olympic Games. There were 44 elite athletes and 68 staff members. The chief physician recorded the symptoms of the common cold daily on a standardised form. Two nasal swabs were taken at the onset of symptoms. One swab was analysed within 45 min using a molecular POCT for respiratory syncytial virus and influenza A and B viruses. After the Games, the other swab was tested for 16 possible causative respiratory viruses using PCR in laboratory-based testing. RESULTS: 20 out of 44 (45%) athletes and 22 out of 68 (32%) staff members experienced symptoms of the common cold during a median stay of 21 days. Eleven (26%) samples tested virus-positive using POCT. All subjects with influenza (n=6) and 32 close contacts were treated with oseltamivir. The aetiology of the common cold was finally detected in 75% of the athletes and 68 % of the staff members. Seven virus clusters were identified. They were caused by coronaviruses 229E, NL63 and OC43, influenza B virus, respiratory syncytial virus A, rhinovirus and human metapneumovirus. The virus infections spread readily within the team, most commonly within the same sport discipline. CONCLUSIONS: The cold was indeed a common illness in Team Finland during the Winter Olympic Games. POCT proved to be clinically valuable, especially for influenza. The aetiology of the common cold was identified in most cases.",2019 Sep 29,"['Valtonen, Maarit', 'Waris, Matti', 'Vuorinen, Tytti', 'Eerola, Erkki', 'Hakanen, Antti J', 'Mjosund, Katja', 'Grönroos, Wilma', 'Heinonen, Olli J', 'Ruuskanen, Olli']",Br J Sports Med,,,True
5072f11488276a2dc8171394942364d59373c743,PMC,Performance evaluation of antimicrobial peptide ll-37 and hepcidin and β-defensin-2 secreted by mesenchymal stem cells,http://dx.doi.org/10.1016/j.heliyon.2019.e02652,PMC6820248,31687504,CC BY-NC-ND,"Peptides are secreted by different cell types and are trendy therapeutic agents that have attracted attention for the treatment of several diseases such as infections. Antimicrobial peptides exert various mechanisms such as changing cell membrane permeability which leads to inhibition or death of bacterial cells. mesenchymal stem cells (MSCs) are key to produce antimicrobial peptides and to inhibit the growth of pathogens. These cells have been shown to be capable of producing antimicrobial peptides upon exposure to different bacteria. As a result, antimicrobial peptides can be considered as novel agents for the treatment of infectious diseases. The purpose of this review was to investigate the targets and mechanisms of antimicrobial peptides secreted by MSCs.",2019 Oct 23,"['Esfandiyari, Reza', 'Halabian, Raheleh', 'Behzadi, Elham', 'Sedighian, Hamid', 'Jafari, Ramezan', 'Imani Fooladi, Abbas Ali']",Heliyon,,,False
4de882602b82e20b2b7d9c7cb136de860a4f8634,PMC,Recovery of TRIM25-Mediated RIG-I Ubiquitination through Suppression of NS1 by RNA Aptamers,http://dx.doi.org/10.14348/molcells.2019.0157,PMC6821451,31600868,CC BY-NC-SA,"Non-structural protein 1 (NS1) of influenza virus has been shown to inhibit the innate immune response by blocking the induction of interferon (IFN). In this study, we isolated two single-stranded RNA aptamers specific to NS1 with K(d) values of 1.62 ± 0.30 nM and 1.97 ± 0.27 nM, respectively, using a systematic evolution of ligand by exponential enrichment (SELEX) procedure. The selected aptamers were able to inhibit the interaction of NS1 with tripartite motif-containing protein 25 (TRIM25), and suppression of NS1 enabled retinoic acid inducible gene I (RIG-I) to be ubiquitinated regularly by TRIM25. Additional luciferase reporter assay and quantitative real-time PCR (RT-PCR) experiments demonstrated that suppression of NS1 by the selected aptamers induced IFN production. It is noted that viral replication was also inhibited through IFN induction in the presence of the selected aptamers. These results suggest that the isolated aptamers are strongly expected to be new therapeutic agents against influenza infection.",2019 Oct 10,"['Woo, Hye-Min', 'Lee, Jin-Moo', 'Kim, Chul-Joong', 'Lee, Jong-Soo', 'Jeong, Yong-Joo']",Mol Cells,,,True
d5aa58e876fa5f90ddab30ed7c410546713d8f01,PMC,Recovery of TRIM25-Mediated RIG-I Ubiquitination through Suppression of NS1 by RNA Aptamers,http://dx.doi.org/10.14348/molcells.2019.0157,PMC6821451,31600868,CC BY-NC-SA,"Non-structural protein 1 (NS1) of influenza virus has been shown to inhibit the innate immune response by blocking the induction of interferon (IFN). In this study, we isolated two single-stranded RNA aptamers specific to NS1 with K(d) values of 1.62 ± 0.30 nM and 1.97 ± 0.27 nM, respectively, using a systematic evolution of ligand by exponential enrichment (SELEX) procedure. The selected aptamers were able to inhibit the interaction of NS1 with tripartite motif-containing protein 25 (TRIM25), and suppression of NS1 enabled retinoic acid inducible gene I (RIG-I) to be ubiquitinated regularly by TRIM25. Additional luciferase reporter assay and quantitative real-time PCR (RT-PCR) experiments demonstrated that suppression of NS1 by the selected aptamers induced IFN production. It is noted that viral replication was also inhibited through IFN induction in the presence of the selected aptamers. These results suggest that the isolated aptamers are strongly expected to be new therapeutic agents against influenza infection.",2019 Oct 10,"['Woo, Hye-Min', 'Lee, Jin-Moo', 'Kim, Chul-Joong', 'Lee, Jong-Soo', 'Jeong, Yong-Joo']",Mol Cells,,,True
ff3db609dbf2669d8d528279ef32280c2646ba85,PMC,More than efficacy revealed by single-cell analysis of antiviral therapeutics,http://dx.doi.org/10.1126/sciadv.aax4761,PMC6821460,31692968,CC BY-NC,"Because many aspects of viral infection dynamics and inhibition are governed by stochastic processes, single-cell analysis should provide more information than approaches using population averaging. We have developed a microfluidic device composed of ~6000 wells, with each well containing a microstructure to capture single, infected cells replicating an enterovirus expressing a fluorescent reporter protein. We have used this system to characterize enterovirus inhibitors with distinct mechanisms of action. Single-cell analysis reveals that each class of inhibitor interferes with the viral infection cycle in a manner that can be distinguished by principal component analysis. Single-cell analysis of antiviral candidates not only reveals efficacy but also facilitates clustering of drugs with the same mechanism of action and provides some indication of the ease with which resistance will develop.",2019 Oct 30,"['Liu, Wu', 'Caglar, Mehmet U.', 'Mao, Zhangming', 'Woodman, Andrew', 'Arnold, Jamie J.', 'Wilke, Claus O.', 'Cameron, Craig E.']",Sci Adv,,,True
f255a3f315fb271531f9dc1f46c33cacf1d18e29,PMC,More than efficacy revealed by single-cell analysis of antiviral therapeutics,http://dx.doi.org/10.1126/sciadv.aax4761,PMC6821460,31692968,CC BY-NC,"Because many aspects of viral infection dynamics and inhibition are governed by stochastic processes, single-cell analysis should provide more information than approaches using population averaging. We have developed a microfluidic device composed of ~6000 wells, with each well containing a microstructure to capture single, infected cells replicating an enterovirus expressing a fluorescent reporter protein. We have used this system to characterize enterovirus inhibitors with distinct mechanisms of action. Single-cell analysis reveals that each class of inhibitor interferes with the viral infection cycle in a manner that can be distinguished by principal component analysis. Single-cell analysis of antiviral candidates not only reveals efficacy but also facilitates clustering of drugs with the same mechanism of action and provides some indication of the ease with which resistance will develop.",2019 Oct 30,"['Liu, Wu', 'Caglar, Mehmet U.', 'Mao, Zhangming', 'Woodman, Andrew', 'Arnold, Jamie J.', 'Wilke, Claus O.', 'Cameron, Craig E.']",Sci Adv,,,False
39a7144b3eb9ddf5b9076163aa61099d8b58f977,PMC,Comparison of Rates of Hospitalization Between Single and Dual Virus Detection in a Mexican Cohort of Children and Adults With Influenza-Like Illness,http://dx.doi.org/10.1093/ofid/ofz424,PMC6824528,31696140,CC BY-NC-ND,"BACKGROUND: Molecular detection methods allow for the simultaneous detection of several infectious agents. This study assesses whether co-infection with 2 viruses as compared with 1 is associated with increased hospitalization in those with acute respiratory infections. METHODS: We prospectively enrolled a cohort of pediatric and adult participants with influenza-like illness during 2010–2014 in Mexico. Clinical information and respiratory samples were collected at enrollment. Respiratory viruses were detected with multiplex polymerase chain reaction (PCR) and influenza-specific reverse transcription PCR assays. Participants were followed for 14 and 28 days after inclusion. Severity of disease, as measured by hospitalization with acute respiratory infections, was compared between single and dual viral infections. RESULTS: Among 5662 participants in the study, either 1 (n = 3285) or 2 (n = 641) viruses were detected in 3926 participants. Rhinovirus (n = 1433), influenza (n = 888), and coronaviruses (n = 703) were the most frequently detected viruses (either alone or in co-infection). Bocavirus, respiratory syncytial virus (RSV), metapneumovirus, and rhinovirus cases were hospitalized more often than other viruses. Bocavirus+rhinovirus cases were hospitalized more often than those with rhinovirus alone (but not bocavirus alone). RSV cases were more likely to be hospitalized than cases with co-infections of RSV and parainfluenza virus or coronavirus. Metapneumovirus cases were hospitalized more often than those co-infected with metapneumovirus+coronavirus. CONCLUSIONS: In this study, detection of 2 viruses did not significantly increase hospitalizations compared with single virus infections. Larger studies will allow for distinguishing between sequential and simultaneous infection and for a better understanding of the role of each virus during the evolution of acute respiratory episodes.",2019 Oct 3,"['Noyola, Daniel E', 'Hunsberger, Sally', 'Valdés Salgado, Raydel', 'Powers, John H', 'Galindo-Fraga, Arturo', 'Ortiz-Hernández, Ana A', 'Ramirez-Venegas, Alejandra', 'Moreno-Espinosa, Sarbelio', 'Llamosas-Gallardo, Beatriz', 'Guerrero, M Lourdes', 'Beigel, John H', 'Ruiz-Palacios, Guillermo', 'Perez-Patrigeon, Santiago', None]",Open Forum Infect Dis,,,True
8b965ccb656960174a81c75effed2a6f2315f0e7,PMC,Predictors of Hematoma Enlargement in Patients with Spontaneous Intracerebral Hemorrhage Treated with Rapid Administration of Antifibrinolytic Agents and Strict Conservative Management,http://dx.doi.org/10.13004/kjnt.2019.15.e23,PMC6826086,31720266,CC BY-NC,"OBJECTIVE: Spontaneous intracerebral hemorrhage (ICH) is caused by the rupture of small blood vessels and other health problems. In ICH patients, hematoma enlargement is the most critical risk factor for poor outcomes. Tranexamic acid, an anti-fibrinolytic agent, has been used to reduce hematoma expansion. We analyzed the risk factors for hematoma expansion in ICH patients and compared the predictability of hematoma expansion in ICH patients with the use of tranexamic acid. METHODS: We performed retrospective analysis of ICH patients who underwent follow-up computed tomography scans from October 2008 to October 2018. Of the 329 included patients, 67 who received tranexamic acid and 262 who did not receive tranexamic acid were compared. We also analyzed the risk factors of 45 and 284 patients who did and did not experience hematoma expansion, respectively. RESULTS: Hematoma expansion was observed in 7 (10.4%) of 67 patients in the tranexamic acid group and 38 (14.5%) of the 262 patients who did not receive tranexamic acid. There was no statistically significant difference between patients who did and did not received tranexamic acid (p=0.389). In the multivariate logistic regression analysis of risk factors for hematoma expansion, spot sign and a maximal diameter of 40 mm were identified as risk factors. CONCLUSION: We could not confirm the effect of tranexamic acid on hematoma expansion in ICH patients. Spot sign and the maximal diameter of hematomas were confirmed as risk factors of hematoma expansion. If the maximal diameter is greater than 40 mm, the hematoma should be closely monitored.",2019 Sep 11,"['Kim, Chang Hyeun', 'Lee, Sang Weon', 'Kim, Young Ha', 'Sung, Soon Ki', 'Son, Dong Wuk', 'Song, Geun Sung']",Korean J Neurotrauma,,,True
14e878a6400d8320e2c781a76edc4a14f4cec1df,PMC,Viral Etiology of Acute Respiratory Infections in Pediatric Patients in Lebanon,http://dx.doi.org/10.4084/MJHID.2019.059,PMC6827722,31700584,CC BY-NC,"BACKGROUND: Acute respiratory infections (ARI) are the leading cause of death worldwide, especially among children. The majority of these infections in children are of viral etiology. In this study, we evaluated the incidence of viral ARI among children in Lebanon. PATIENTS AND METHODS: Children presenting with symptoms of ARI were prospectively recruited between September 2009 to February 2012. Nasopharyngeal aspirates were obtained from patients and screened for 11 respiratory viruses using a multiplex Luminex-based PCR assay. RESULTS: Two hundred twenty-one patients were recruited with a median age of 1 year (IQR: 0 – 5). Out of 221 patients, 116 (52.5%) were positive for at least one virus, the majority (103/116; 88.8%) of which were in children under 6-year of age. Overall, 188 viruses were detected. Rhinovirus (RhV) was the most common virus detected in 81 (69.8%) patients followed by coxsackie virus and echovirus (CVEV) which were detected as one target in the panel in 45 (38.8%), and parainfluenza viruses (PIV types: 1, 2, 3, 4) in 24 (20.7%) patients. Coinfection with more than one virus was detected in 49 (42.9%) patients. RhV and CVEV were the most common viruses associated with co-infections and higher risk of rhinorrhea. CONCLUSIONS: Viral pathogens account for at least half of the ARIs in Lebanon, with a high frequency of co-infections being detected.",2019 Nov 1,"['Masoud, Khaldoun', 'Hanna-Wakim, Rima', 'Zaraket, Hassan', 'Kharroubi, Samer', 'Araj, George F', 'Matar, Ghassan M', 'Dbaibo, Ghassan']",Mediterr J Hematol Infect Dis,,,True
778e12208f719a2e26d1387a5a489cdc93c612f4,PMC,Association between syphilis seroprevalence and age among blood donors in Southern China: an observational study from 2014 to 2017,http://dx.doi.org/10.1136/bmjopen-2018-024393,PMC6830658,31678932,CC BY-NC,"OBJECTIVE: This study investigated the association between syphilis seroprevalence and age among blood donors, and described the distribution of serological titres among syphilis-infected donors, aiming to confirm the syphilis epidemic characteristics and to promote effective interventions for older adults. METHODS: Data were obtained from the Shenzhen Programme for Syphilis Prevention and Control in 2014–2017. Blood samples were screened using the ELISAs, and confirmed using the Treponema pallidum particle agglutination assay (TPPA) and toluidine red unheated serum test (TRUST). RESULTS: Among 394 792 blood donors, 733 tested TPPA and TRUST positive (active infection), and 728 tested only TPPA positive (historical infection). The overall prevalence of syphilis seropositivity was 370.1 per 100 000 (95% CI 351.1 to 389.0 per 100 000); the prevalence of active infection was 185.7 per 100 000 (95% CI 172.2 to 199.1 per 100 000). People aged ≥45 years displayed a prevalence of 621.8 per 100 000 in syphilis seropositivity and 280.5 per 100 000 in active infection, which were 3.8 times and 2.4 times higher than that for people aged <25 years, respectively. The prevalence of syphilis seropositivity (χ(2) (trend)=311.9, p (trend)<0.001) and active infection (χ(2) (trend)=72.1, p (trend)<0.001) increased significantly with age. After stratification by gender and year of donation, the increasing trend of prevalence with age remained (p (trend)<0.05), except for the prevalence of active infection in males and females in 2014. About 16.3% of donors with active infection and aged ≥45 years had a TRUST titre of ≥1∶8, lower than that of patients aged <25 years (51.3%) and 25–34 years (34.1%). CONCLUSIONS: The findings confirm the high prevalence of syphilis among older adults, and suggest the need to increase awareness among healthcare providers and deliver more targeted prevention interventions for older adults to promote early testing.",2019 Nov 2,"['Wu, Xiaobing', 'Guan, Yang', 'Ye, Jianbin', 'Fu, Hanlin', 'Zhang, Chunlai', 'Lan, Lina', 'Wu, Fengxin', 'Tang, Fen', 'Wang, Feng', 'Cai, Yumao', 'Yu, Weiye', 'Feng, Tiejian']",BMJ Open,,,True
56f69c9790f32dd7649fa2e14be26ae099321ee6,PMC,Association between syphilis seroprevalence and age among blood donors in Southern China: an observational study from 2014 to 2017,http://dx.doi.org/10.1136/bmjopen-2018-024393,PMC6830658,31678932,CC BY-NC,"OBJECTIVE: This study investigated the association between syphilis seroprevalence and age among blood donors, and described the distribution of serological titres among syphilis-infected donors, aiming to confirm the syphilis epidemic characteristics and to promote effective interventions for older adults. METHODS: Data were obtained from the Shenzhen Programme for Syphilis Prevention and Control in 2014–2017. Blood samples were screened using the ELISAs, and confirmed using the Treponema pallidum particle agglutination assay (TPPA) and toluidine red unheated serum test (TRUST). RESULTS: Among 394 792 blood donors, 733 tested TPPA and TRUST positive (active infection), and 728 tested only TPPA positive (historical infection). The overall prevalence of syphilis seropositivity was 370.1 per 100 000 (95% CI 351.1 to 389.0 per 100 000); the prevalence of active infection was 185.7 per 100 000 (95% CI 172.2 to 199.1 per 100 000). People aged ≥45 years displayed a prevalence of 621.8 per 100 000 in syphilis seropositivity and 280.5 per 100 000 in active infection, which were 3.8 times and 2.4 times higher than that for people aged <25 years, respectively. The prevalence of syphilis seropositivity (χ(2) (trend)=311.9, p (trend)<0.001) and active infection (χ(2) (trend)=72.1, p (trend)<0.001) increased significantly with age. After stratification by gender and year of donation, the increasing trend of prevalence with age remained (p (trend)<0.05), except for the prevalence of active infection in males and females in 2014. About 16.3% of donors with active infection and aged ≥45 years had a TRUST titre of ≥1∶8, lower than that of patients aged <25 years (51.3%) and 25–34 years (34.1%). CONCLUSIONS: The findings confirm the high prevalence of syphilis among older adults, and suggest the need to increase awareness among healthcare providers and deliver more targeted prevention interventions for older adults to promote early testing.",2019 Nov 2,"['Wu, Xiaobing', 'Guan, Yang', 'Ye, Jianbin', 'Fu, Hanlin', 'Zhang, Chunlai', 'Lan, Lina', 'Wu, Fengxin', 'Tang, Fen', 'Wang, Feng', 'Cai, Yumao', 'Yu, Weiye', 'Feng, Tiejian']",BMJ Open,,,True
92a5a662e916fd3d1520764cbfca4ad457dd09d7,PMC,Association between syphilis seroprevalence and age among blood donors in Southern China: an observational study from 2014 to 2017,http://dx.doi.org/10.1136/bmjopen-2018-024393,PMC6830658,31678932,CC BY-NC,"OBJECTIVE: This study investigated the association between syphilis seroprevalence and age among blood donors, and described the distribution of serological titres among syphilis-infected donors, aiming to confirm the syphilis epidemic characteristics and to promote effective interventions for older adults. METHODS: Data were obtained from the Shenzhen Programme for Syphilis Prevention and Control in 2014–2017. Blood samples were screened using the ELISAs, and confirmed using the Treponema pallidum particle agglutination assay (TPPA) and toluidine red unheated serum test (TRUST). RESULTS: Among 394 792 blood donors, 733 tested TPPA and TRUST positive (active infection), and 728 tested only TPPA positive (historical infection). The overall prevalence of syphilis seropositivity was 370.1 per 100 000 (95% CI 351.1 to 389.0 per 100 000); the prevalence of active infection was 185.7 per 100 000 (95% CI 172.2 to 199.1 per 100 000). People aged ≥45 years displayed a prevalence of 621.8 per 100 000 in syphilis seropositivity and 280.5 per 100 000 in active infection, which were 3.8 times and 2.4 times higher than that for people aged <25 years, respectively. The prevalence of syphilis seropositivity (χ(2) (trend)=311.9, p (trend)<0.001) and active infection (χ(2) (trend)=72.1, p (trend)<0.001) increased significantly with age. After stratification by gender and year of donation, the increasing trend of prevalence with age remained (p (trend)<0.05), except for the prevalence of active infection in males and females in 2014. About 16.3% of donors with active infection and aged ≥45 years had a TRUST titre of ≥1∶8, lower than that of patients aged <25 years (51.3%) and 25–34 years (34.1%). CONCLUSIONS: The findings confirm the high prevalence of syphilis among older adults, and suggest the need to increase awareness among healthcare providers and deliver more targeted prevention interventions for older adults to promote early testing.",2019 Nov 2,"['Wu, Xiaobing', 'Guan, Yang', 'Ye, Jianbin', 'Fu, Hanlin', 'Zhang, Chunlai', 'Lan, Lina', 'Wu, Fengxin', 'Tang, Fen', 'Wang, Feng', 'Cai, Yumao', 'Yu, Weiye', 'Feng, Tiejian']",BMJ Open,,,True
298f292239fa60b67bc08c1e1098cff747aa8f15,PMC,The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus,http://dx.doi.org/10.1016/j.isci.2019.07.003,PMC6831822,31402258,CC BY-NC-ND,"Here, we show that the US Food and Drug Administration-approved oral drug nitazoxanide (NTZ) broadly amplifies the host innate immune response to viruses and inhibits Ebola virus (EBOV) replication. We find that NTZ enhances retinoic-acid-inducible protein I (RIG-I)-like-receptor, mitochondrial antiviral signaling protein, interferon regulatory factor 3, and interferon activities and induces transcription of the antiviral phosphatase GADD34. NTZ significantly inhibits EBOV replication in human cells through its effects on RIG-I and protein kinase R (PKR), suggesting that it counteracts EBOV VP35 protein's ability to block RIG-I and PKR sensing of EBOV. NTZ also inhibits a second negative-strand RNA virus, vesicular stomatitis virus (VSV), through RIG-I and GADD34, but not PKR, consistent with VSV's distinct host innate immune evasion mechanisms. Thus, NTZ counteracts varied virus-specific immune evasion strategies by generally enhancing the RNA sensing and interferon axis that is triggered by foreign cytoplasmic RNA exposure, and holds promise as an oral therapy against EBOV.",2019 Aug 8,"['Jasenosky, Luke D.', 'Cadena, Cristhian', 'Mire, Chad E.', 'Borisevich, Viktoriya', 'Haridas, Viraga', 'Ranjbar, Shahin', 'Nambu, Aya', 'Bavari, Sina', 'Soloveva, Veronica', 'Sadukhan, Supriya', 'Cassell, Gail H.', 'Geisbert, Thomas W.', 'Hur, Sun', 'Goldfeld, Anne E.']",iScience,,,False
af0442df28de9051b460e903b513afc2a13b54a4,PMC,The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus,http://dx.doi.org/10.1016/j.isci.2019.07.003,PMC6831822,31402258,CC BY-NC-ND,"Here, we show that the US Food and Drug Administration-approved oral drug nitazoxanide (NTZ) broadly amplifies the host innate immune response to viruses and inhibits Ebola virus (EBOV) replication. We find that NTZ enhances retinoic-acid-inducible protein I (RIG-I)-like-receptor, mitochondrial antiviral signaling protein, interferon regulatory factor 3, and interferon activities and induces transcription of the antiviral phosphatase GADD34. NTZ significantly inhibits EBOV replication in human cells through its effects on RIG-I and protein kinase R (PKR), suggesting that it counteracts EBOV VP35 protein's ability to block RIG-I and PKR sensing of EBOV. NTZ also inhibits a second negative-strand RNA virus, vesicular stomatitis virus (VSV), through RIG-I and GADD34, but not PKR, consistent with VSV's distinct host innate immune evasion mechanisms. Thus, NTZ counteracts varied virus-specific immune evasion strategies by generally enhancing the RNA sensing and interferon axis that is triggered by foreign cytoplasmic RNA exposure, and holds promise as an oral therapy against EBOV.",2019 Aug 8,"['Jasenosky, Luke D.', 'Cadena, Cristhian', 'Mire, Chad E.', 'Borisevich, Viktoriya', 'Haridas, Viraga', 'Ranjbar, Shahin', 'Nambu, Aya', 'Bavari, Sina', 'Soloveva, Veronica', 'Sadukhan, Supriya', 'Cassell, Gail H.', 'Geisbert, Thomas W.', 'Hur, Sun', 'Goldfeld, Anne E.']",iScience,,,False
6e8fa242b79e0687b11c09dc305227edce302d7d,PMC,Understanding temporal and spatial variations of viral disease in the US: The need for a one-health-based data collection and analysis approach,http://dx.doi.org/10.1016/j.onehlt.2019.100105,PMC6831848,31709295,CC BY-NC-ND,"Viral diseases exhibit spatial and temporal variation, and there are many factors that can affect their occurrence. The identification of these factors is critical in the efforts to predict and lessen viral disease burden. Because viral infection is able to spread to humans from the environment, animals, and other humans, the One-Health framework can be used to investigate the critical pathways through which viruses are transported and transmitted. A holistic approach, incorporating publicly available clinical data for human, livestock, and wildlife disease occurrence, together with environmental data reported in federal and state databases such as parameters related to land use, environmental quality, and weather, can enhance the understanding of variations in disease patterns, leading to the design and implementation of surveillance systems. An example analysis approach is presented for Michigan, United States, which is a state with large urban centers as well as a sizeable rural and agricultural population. Analysis of publicly available data from 2017 indicates that gastrointestinal (GI) and influenza-associated illnesses in Michigan may have been related with agricultural land use to a higher extent than with developed land use during that year. Meanwhile, hepatitis A virus appears to be most closely related with developed land use in dense population areas. GI illnesses may be related to precipitation, and this relationship is strongest in the springtime, although GI illnesses are most common in the winter months. Integration of human-related clinical data, animal disease data, and environmental data can ultimately be used for prioritization of the most critical locations and times for viral outbreaks in both urban and rural environments.",2019 Oct 19,"[""O'Brien, Evan"", 'Xagoraraki, Irene']",One Health,,,False
4aaa3a3f99f42247cde4c7dced85ce317c19384b,PMC,A rare case of CMV pneumonia in HIV-infection,http://dx.doi.org/10.1016/j.rmcr.2019.100945,PMC6831852,31709138,CC BY-NC-ND,"Cytomegalovirus (CMV) pneumonia is a rare opportunistic infection in the setting of HIV (Human Immunodeficiency Virus)-infection. Establishing accurate diagnosis of CMV pneumonia in HIV-infection can be challenging. Co-infections by multiple opportunistic pathogens are common and a high degree of clinical vigilance to evaluate for multiple infections, including CMV pneumonia, should be maintained. As there can be a degree of overlap in clinical and radiological features amongst different opportunistic infections affecting the lungs, definitive microbiological and cytohistologic evidences are needed. Reliance on microbiological evidence of CMV in respiratory specimens alone for the diagnosis of CMV pneumonia will lead to an over-diagnosis of the condition and unnecessary treatment. In our case report, we describe a 53-year-old man with recently diagnosed HIV-infection who presented with non-resolving pneumonia. A diagnosis of CMV pneumonia was reached through consistent clinical, radiological, microbiological and cytologic investigations. The patient made a full clinical recovery after being started on anti-CMV treatment.",2019 Oct 16,"['Poh, Kai Chin', 'Zheng, Shuwei']",Respir Med Case Rep,,,False
afa4ca223097866f6e31d75570448a22db0f72c5,PMC,Estimation Of Direct Medical Costs Of Middle East Respiratory Syndrome Coronavirus Infection: A Single-Center Retrospective Chart Review Study,http://dx.doi.org/10.2147/IDR.S231087,PMC6844224,31819541,CC BY-NC,"BACKGROUND: Among the countries affected by Middle East respiratory syndrome (MERS), Saudi Arabia was impacted the most, with 2,058 cases reported as of June 2019. However, the impact of the MERS epidemic on the Saudi economy is unknown. PURPOSE: The present study aimed to evaluate the direct medical costs associated with the management of MERS cases at a tertiary referral hospital in Riyadh, Saudi Arabia. METHODS: The study involved a retrospective chart review of confirmed cases of MERS coronavirus (MERS-CoV) infections in a tertiary care referral center in Riyadh, Saudi Arabia, from January 2015 to October 2018. The collected data included sociodemographic characteristics, medical information, and the cost of hospitalization of each patient as estimated by micro-costing. RESULTS: A complete set of relevant information was available only for 24 of 44 identified MERS-CoV cases. Patients were mostly females, and the mean age was 52 years. Diabetes, hypertension, and chronic kidney disease were the most frequent comorbidities. The length of hospital stay varied from 1 to 31 days, averaging 4.96 ± 7.29 days. Two of the 24 patients died. The total cost of managing a MERS case at the hospital ranged from $1278.41 to $75,987.95 with a mean cost of $12,947.03 ± $19,923.14. CONCLUSION: The findings of this study highlight the enormous expenses incurred by the Saudi health care system due to the MERS-CoV outbreak and the importance of developing an enforceable nationwide policy to control MERS-CoV transmission and infection.",2019 Nov 7,"['AlRuthia, Yazed', 'Somily, Ali M', 'Alkhamali, Amal S', 'Bahari, Ohud H', 'AlJuhani, Raneem J', 'Alsenaidy, Mohammad', 'Balkhi, Bander']",Infect Drug Resist,,,True
802c4e9e532b2a48928179795754847a229252ec,PMC,Bornaviruses in naturally infected Psittacus erithacus in Portugal: insights of molecular epidemiology and ecology,http://dx.doi.org/10.1080/20008686.2019.1685632,PMC6844444,31741722,CC BY-NC,"Background: The genus Orthobornavirus comprises non-segmented, negative-stranded RNA viruses able to infect humans, mammals, reptiles and various birds. Parrot bornavirus 1 to 8 (PaBV-1 to 8) causes neurological and/or gastrointestinal syndromes and death on psittacines. We aimed to identify and to produce epidemiologic knowledge about the etiologic agent associated with a death of two female Psittacus erithacus (grey parrot). Methods and Results: Both parrots were submitted for a complete standardised necropsy. Tissue samples were analysed by PCR. The findings in necropsy were compatible with bornavirus infection. Analysis revealed PaBV-4 related with genotypes detected in captive and in wild birds. The N and X proteins of PaBV-4 were more related to avian bornaviruses, while phosphoprotein was more related to variegated squirrel bornavirus 1 (VSBV-1). Within the P gene/phosphoprotein a highly conserved region between and within bornavirus species was found. Conclusions: Portugal is on the routes of the intensive world trade of psittacines. Broad screening studies are required to help understanding the role of wild birds in the emergence and spread of pathogenic bornaviruses. PaBV-4 phosphoprotein is closer to VSBV-1 associated with lethal encephalitis in humans than with some of the avian bornaviruses. The highly conserved P gene/phosphoprotein region is a good target for molecular diagnostics screenings.",2019 Nov 6,"['Pinto, Marlene Cavaleiro', 'Craveiro, Hélder', 'Johansson Wensman, Jonas', 'Carvalheira, Júlio', 'Berg, Mikael', 'Thompson, Gertrude']",Infect Ecol Epidemiol,,,True
51d37c55030f7c7570f83c8a75f5e6a97209a6c5,PMC,Intensive Care Unit Relocation and Its Effect on Multidrug-Resistant Respiratory Microorganisms,http://dx.doi.org/10.4266/acc.2018.00220,PMC6849029,31723891,CC BY-NC,"BACKGROUND: Infection by multidrug-resistant (MDR) pathogens leads to poor patient outcomes in intensive care units (ICUs). Contact precautions are necessary to reduce the transmission of MDR pathogens. However, the importance of the surrounding environment is not well known. We studied the effects of ICU relocation on MDR respiratory pathogen detection rates and patient outcomes. METHODS: Patients admitted to the ICU before and after the relocation were retrospectively analyzed. Baseline patient characteristics, types of respiratory pathogens detected, antibiotics used, and patient outcomes were measured. RESULTS: A total of 463 adult patients admitted to the ICU, 4 months before and after the relocation, were included. Of them, 234 were admitted to the ICU before the relocation and 229 afterward. Baseline characteristics, including age, sex, and underlying comorbidities, did not differ between the two groups. After the relocation, the incidence rate of MDR respiratory pathogen detection decreased from 90.0 to 68.8 cases per 1,000 patient-days, but that difference was statistically insignificant. The use of colistin was significantly reduced from 53.5 days (95% confidence interval [CI], 20.3 to 86.7 days) to 18.7 days (95% CI, 5.6 to 31.7 days). Furthermore, the duration of hospital stay was significantly reduced from a median of 29 days (interquartile range [IQR], 14 to 50 days) to 21 days (IQR, 11 to 39 days). CONCLUSIONS: Incidence rates of MDR respiratory pathogen detection were not significantly different before and after ICU relocation. However, ICU relocation could be helpful in reducing the use of antibiotics against MDR pathogens and improving patient outcomes.",2018 Nov 14,"['Kim, Hyung-Jun', 'Jeong, EuiSeok', 'Choe, Pyoeng Gyun', 'Lee, Sang-Min', 'Lee, Jinwoo']",Acute Crit Care,,,True
46914e767ad2dad4be0e39ae051c645fdea70666,PMC,Intensive Care Unit Relocation and Its Effect on Multidrug-Resistant Respiratory Microorganisms,http://dx.doi.org/10.4266/acc.2018.00220,PMC6849029,31723891,CC BY-NC,"BACKGROUND: Infection by multidrug-resistant (MDR) pathogens leads to poor patient outcomes in intensive care units (ICUs). Contact precautions are necessary to reduce the transmission of MDR pathogens. However, the importance of the surrounding environment is not well known. We studied the effects of ICU relocation on MDR respiratory pathogen detection rates and patient outcomes. METHODS: Patients admitted to the ICU before and after the relocation were retrospectively analyzed. Baseline patient characteristics, types of respiratory pathogens detected, antibiotics used, and patient outcomes were measured. RESULTS: A total of 463 adult patients admitted to the ICU, 4 months before and after the relocation, were included. Of them, 234 were admitted to the ICU before the relocation and 229 afterward. Baseline characteristics, including age, sex, and underlying comorbidities, did not differ between the two groups. After the relocation, the incidence rate of MDR respiratory pathogen detection decreased from 90.0 to 68.8 cases per 1,000 patient-days, but that difference was statistically insignificant. The use of colistin was significantly reduced from 53.5 days (95% confidence interval [CI], 20.3 to 86.7 days) to 18.7 days (95% CI, 5.6 to 31.7 days). Furthermore, the duration of hospital stay was significantly reduced from a median of 29 days (interquartile range [IQR], 14 to 50 days) to 21 days (IQR, 11 to 39 days). CONCLUSIONS: Incidence rates of MDR respiratory pathogen detection were not significantly different before and after ICU relocation. However, ICU relocation could be helpful in reducing the use of antibiotics against MDR pathogens and improving patient outcomes.",2018 Nov 14,"['Kim, Hyung-Jun', 'Jeong, EuiSeok', 'Choe, Pyoeng Gyun', 'Lee, Sang-Min', 'Lee, Jinwoo']",Acute Crit Care,,,False
ed6b1dc674893e435945a5efbd1eef13a7c56bc1,PMC,"Study on inactivation of porcine epidemic diarrhoea virus, porcine sapelovirus 1 and adenovirus in the production and storage of laboratory spray‐dried porcine plasma",http://dx.doi.org/10.1111/jam.14235,PMC6849764,30803120,CC BY-NC-ND,"AIM: Evaluation of the thermal and physical conditions for inactivation of adenovirus (AdV), porcine sapelovirus 1 (PSV1) and the economically important viruses porcine epidemic diarrhoea virus (PEDV) and porcine circovirus 2 (PCV2) in the production of spray‐dried porcine plasma (SDPP). METHODS AND RESULTS: Citrate‐treated porcine plasma of pH 7·5, 9·8 and 10·2 (8·5% dry‐matter) was spiked with PEDV, PSV1, PCV2 and AdV and incubated at 3°C for maximum 24 h, and at 44 or 48°C for maximum 10 min (Experiment 1). Spiked citrate‐treated concentrated plasma of pH 7·5 and 9·8 (24% dry‐matter) was spray dried in a laboratory scale apparatus (Experiment 2). Aliquots of SDPP were stored over a period of 0–10 weeks at 11 and 20°C (Experiment 3). Reverse transcription(RT)‐quantitative PCR detected no notable reduction in viral genomes in treated plasma and SDPP samples. No infectious PSV1 was re‐isolated from plasma and SDPP samples in cell culture. At pH 10·2 and 3°C, infectivity of PEDV in plasma was reduced with a reduction factor of 4·2 log 10 (LRF) at 10 h contact time, whereas heating to 44°C for at least 1 min at alkali pH was needed to achieve a LRF of 4·2 for AdV. Spray drying at an outlet temperature of 80°C reduced AdV infectivity effectively (LRF = 5·2) and PEDV infectivity for 95% (LRF = 1·4). After storage at 20°C for 2 weeks no infectious PEDV was re‐isolated from SDPP anymore (LRF ≥4·0). Due to growth of antibiotic‐resistant bacteria from plasma in cell cultures used for PCV2 isolation, no data regarding inactivation of PCV2 were obtained. CONCLUSIONS: Five percent of PEDV stayed infectious after our spray drying conditions. Spray drying in combination with storage for ≥2 weeks at 20°C eliminated infectivity of PEDV effectively. SIGNIFICANCE AND IMPACT OF THE STUDY: The conditions for inactivation of virus in plasma and SDPP determined are important for producers to inactivate PEDV during production of SDPP.",2019 Jun 1,"['Hulst, M.M.', 'Heres, L.', 'Hakze‐van der Honing, R.W.', 'Pelser, M.', 'Fox, M.', 'van der Poel, W.H.M.']",J Appl Microbiol,,,True
ecdc56575a3711cd6b7f3207098bae3b82fd79a4,PMC,"Study on inactivation of porcine epidemic diarrhoea virus, porcine sapelovirus 1 and adenovirus in the production and storage of laboratory spray‐dried porcine plasma",http://dx.doi.org/10.1111/jam.14235,PMC6849764,30803120,CC BY-NC-ND,"AIM: Evaluation of the thermal and physical conditions for inactivation of adenovirus (AdV), porcine sapelovirus 1 (PSV1) and the economically important viruses porcine epidemic diarrhoea virus (PEDV) and porcine circovirus 2 (PCV2) in the production of spray‐dried porcine plasma (SDPP). METHODS AND RESULTS: Citrate‐treated porcine plasma of pH 7·5, 9·8 and 10·2 (8·5% dry‐matter) was spiked with PEDV, PSV1, PCV2 and AdV and incubated at 3°C for maximum 24 h, and at 44 or 48°C for maximum 10 min (Experiment 1). Spiked citrate‐treated concentrated plasma of pH 7·5 and 9·8 (24% dry‐matter) was spray dried in a laboratory scale apparatus (Experiment 2). Aliquots of SDPP were stored over a period of 0–10 weeks at 11 and 20°C (Experiment 3). Reverse transcription(RT)‐quantitative PCR detected no notable reduction in viral genomes in treated plasma and SDPP samples. No infectious PSV1 was re‐isolated from plasma and SDPP samples in cell culture. At pH 10·2 and 3°C, infectivity of PEDV in plasma was reduced with a reduction factor of 4·2 log 10 (LRF) at 10 h contact time, whereas heating to 44°C for at least 1 min at alkali pH was needed to achieve a LRF of 4·2 for AdV. Spray drying at an outlet temperature of 80°C reduced AdV infectivity effectively (LRF = 5·2) and PEDV infectivity for 95% (LRF = 1·4). After storage at 20°C for 2 weeks no infectious PEDV was re‐isolated from SDPP anymore (LRF ≥4·0). Due to growth of antibiotic‐resistant bacteria from plasma in cell cultures used for PCV2 isolation, no data regarding inactivation of PCV2 were obtained. CONCLUSIONS: Five percent of PEDV stayed infectious after our spray drying conditions. Spray drying in combination with storage for ≥2 weeks at 20°C eliminated infectivity of PEDV effectively. SIGNIFICANCE AND IMPACT OF THE STUDY: The conditions for inactivation of virus in plasma and SDPP determined are important for producers to inactivate PEDV during production of SDPP.",2019 Jun 1,"['Hulst, M.M.', 'Heres, L.', 'Hakze‐van der Honing, R.W.', 'Pelser, M.', 'Fox, M.', 'van der Poel, W.H.M.']",J Appl Microbiol,,,False
32b8b12a0247b3413442631d5a1bee05a4e5d689,PMC,How do we … integrate pathogen reduced platelets into our hospital blood bank inventory?,http://dx.doi.org/10.1111/trf.15241,PMC6850142,30883807,CC BY-NC-ND,"For more than 50 years there has been an ongoing effort to combat transfusion‐transmitted infections and provide patients with the safest possible blood. This initiative has driven much of the research within the transfusion community. Initial methods included screening donors for travel histories to banned areas and for high‐risk behaviors, but pathogen‐specific assays performed at the collection and manufacturing sites also have become key factors in assuring blood safety. Many of these have focused on donor and laboratory‐based screening for transfusion‐transmitted diseases, as evidenced by the hepatitis and human immunodeficiency virus screening in the 1970s, 1980s, and 1990s. More recently, this effort has expanded to develop donor screening assays to identify other blood‐borne pathogens, such as Zika and West Nile viruses and Babesia. Bacterial contamination of units of platelets (PLTs), however, remains a significant concern. In recent years, the Food and Drug Administration has approved rapid tests to identify bacterially contaminated PLT units in the blood bank before transfusion. Other supplemental methods have been developed, however, that aim to inactivate blood‐borne pathogen(s) present in the blood product, rather than to rely on our ability to identify and interdict contaminated and infected components. Pathogen reduction technology, as this is referred to, provides a proactive way to further reduce the risk posed by transfusion‐transmitted infections.",2019 May 18,"['Rutter, Sara', 'Snyder, Edward L.']",Transfusion,,,True
b233ca2dc15696ccb328ab3eed768e1ec006f55a,PMC,From farm management to bacteriophage therapy: strategies to reduce antibiotic use in animal agriculture,http://dx.doi.org/10.1111/nyas.14034,PMC6850639,30924542,CC BY-NC,"To reduce the use of antibiotics in animal agriculture, a number of effective or commercially viable alternatives have been implemented by food animal producers or are under development. Perhaps the most well‐established strategies are flock and herd management practices to mitigate disease introduction and spread, and, subsequently, reduce the need for antibiotic use. While vaccines in food animal production have been used to prevent both bacterial and viral diseases, but historically, most vaccines have targeted viral diseases. Though vaccines against viral diseases can help reduce the need for antibiotic use by controlling the spread of secondary bacterial infections, more recent vaccines under development specifically target bacteria. New developments in selecting and potentially tailoring bacteriophages provide a promising avenue for controlling pathogenic bacteria without the need for traditional small‐molecule antibiotics. In this article we discuss these established and emerging strategies, which are anticipated to reduce the reliance on antibiotics in food animal production and should reduce the prevalence and transmission to humans of antimicrobial resistant bacteria from these systems.",2019 Apr 29,"['Kahn, Laura H.', 'Bergeron, Gilles', 'Bourassa, Megan W.', 'De Vegt, Bert', 'Gill, Jason', 'Gomes, Filomena', 'Malouin, François', 'Opengart, Ken', 'Ritter, G. Donald', 'Singer, Randall S.', 'Storrs, Carina', 'Topp, Edward']",Ann N Y Acad Sci,,,True
abd53dcf1f9552913a4e99b759c0df469577d5b5,PMC,Systemic resilience to cross‐border infectious disease threat events in Europe,http://dx.doi.org/10.1111/tbed.13211,PMC6852001,31022321,CC BY-NC-ND,"Recurrent health emergencies threaten global health security. International Health Regulations (IHR) aim to prevent, detect and respond to such threats, through increase in national public health core capacities, but whether IHR core capacity implementation is necessary and sufficient has been contested. With a longitudinal study we relate changes in national IHR core capacities to changes in cross‐border infectious disease threat events (IDTE) between 2010 and 2016, collected through epidemic intelligence at the European Centre for Disease Prevention and Control (ECDC). By combining all IHR core capacities into one composite measure we found that a 10% increase in the mean of this composite IHR core capacity to be associated with a 19% decrease (p = 0.017) in the incidence of cross‐border IDTE in the EU. With respect to specific IHR core capacities, an individual increase in national legislation, policy & financing; coordination and communication with relevant sectors; surveillance; response; preparedness; risk communication; human resource capacity; or laboratory capacity was associated with a significant decrease in cross‐border IDTE incidence. In contrast, our analysis showed that IHR core capacities relating to point‐of‐entry, zoonotic events or food safety were not associated with IDTE in the EU. Due to high internal correlations between core capacities, we conducted a principal component analysis which confirmed a 20% decrease in risk of IDTE for every 10% increase in the core capacity score (95% CI: 0.73, 0.88). Globally (EU excluded), a 10% increase in the mean of all IHR core capacities combined was associated with a 14% decrease (p = 0.077) in cross‐border IDTE incidence. We provide quantitative evidence that improvements in IHR core capacities at country‐level are associated with fewer cross‐border IDTE in the EU, which may also hold true for other parts of the world.",2019 Sep 17,"['Semenza, Jan C.', 'Sewe, Maquines Odhiambo', 'Lindgren, Elisabet', 'Brusin, Sergio', 'Aaslav, Kaja Kaasik', 'Mollet, Thomas', 'Rocklöv, Joacim']",Transbound Emerg Dis,,,True
9ddb63e47ae59fb8d315bfe119d9a1a3426af592,PMC,Detection of selected viral pathogens in dogs with canine infectious respiratory disease in Austria,http://dx.doi.org/10.1111/jsap.13051,PMC6852529,31301071,CC BY-NC-ND,"OBJECTIVES: To assess the prevalence of canine parainfluenza virus, canine adenovirus type 2, canine distemper virus, canine respiratory coronavirus and influenza virus A infections in: (1) privately‐owned or, (2) kennelled dogs showing signs consistent with canine infectious respiratory disease and, (3) clinically healthy dogs in Vienna, Austria. MATERIALS AND METHODS: Prospectively, nasal and tonsillar swabs from 214 dogs affected with infectious respiratory disease, and 50 healthy control dogs were tested for nucleic acids specific to the various viral infections. Concurrent bronchoalveolar lavage fluid from 31 dogs with chronic respiratory disease was investigated for the same viral pathogens. Additionally, anti‐canine respiratory coronavirus antibody concentrations were measured in paired blood samples from 30 acutely diseased dogs. RESULTS: Canine respiratory coronavirus (7.5%) and canine parainfluenza virus (6.5%) were the most commonly detected viruses in samples from the upper airways of dogs with respiratory infections. Serological results showed a significant seroconversion in response to coronavirus in 50% of the examined cases. None of the samples was positive for influenza virus A‐specific nucleic acid. Canine coronavirus‐specific nucleic acid was detected in 4.0% of healthy dogs. CLINICAL SIGNIFICANCE: Canine coronavirus should be considered as a clinically relevant cause of infectious respiratory disease in crowded dog populations. For sample collection, the nasal mucosa can be recommended as the favoured site. Analysis of paired serum samples aids verification of canine coronavirus infection in respiratory disease.",2019 Oct 12,"['Hiebl, A.', 'Auer, A.', 'Bagrinovschi, G.', 'Stejskal, M.', 'Hirt, R.', 'Rümenapf, H. T.', 'Tichy, A.', 'Künzel, F.']",J Small Anim Pract,,,True
264fb27c70d421557131f4ec462c56c8378217ef,PMC,Impaired inflammasome activation and bacterial clearance in G6PD deficiency due to defective NOX/p38 MAPK/AP-1 redox signaling,http://dx.doi.org/10.1016/j.redox.2019.101363,PMC6854078,31707353,CC BY-NC-ND,"Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway that modulates cellular redox homeostasis via the regeneration of NADPH. G6PD-deficient cells have a reduced ability to induce the innate immune response, thus increasing host susceptibility to pathogen infections. An important part of the immune response is the activation of the inflammasome. G6PD-deficient peripheral blood mononuclear cells (PBMCs) from patients and human monocytic (THP-1) cells were used as models to investigate whether G6PD modulates inflammasome activation. A decreased expression of IL-1β was observed in both G6PD-deficient PBMCs and PMA-primed G6PD-knockdown (G6PD-kd) THP-1 cells upon lipopolysaccharide (LPS)/adenosine triphosphate (ATP) or LPS/nigericin stimulation. The pro-IL-1β expression of THP-1 cells was decreased by G6PD knockdown at the transcriptional and translational levels in an investigation of the expression of the inflammasome subunits. The phosphorylation of p38 MAPK and downstream c-Fos expression were decreased upon G6PD knockdown, accompanied by decreased AP-1 translocation into the nucleus. Impaired inflammasome activation in G6PD-kd THP-1 cells was mediated by a decrease in the production of reactive oxygen species (ROS) by NOX signaling, while treatment with hydrogen peroxide (H(2)O(2)) enhanced inflammasome activation in G6PD-kd THP-1 cells. G6PD knockdown decreased Staphylococcus aureus and Escherichia coli clearance in G6PD-kd THP-1 cells and G6PD-deficient PBMCs following inflammasome activation. These findings support the notion that enhanced pathogen susceptibility in G6PD deficiency is, in part, due to an altered redox signaling, which adversely affects inflammasome activation and the bactericidal response.",2019 Nov 2,"['Yen, Wei-Chen', 'Wu, Yi-Hsuan', 'Wu, Chih-Ching', 'Lin, Hsin-Ru', 'Stern, Arnold', 'Chen, Shih-Hsiang', 'Shu, Jwu-Ching', 'Tsun-Yee Chiu, Daniel']",Redox Biol,,,False
fe7f73942f37c95d1cce92b35d0176c9bc11c138,PMC,Impaired inflammasome activation and bacterial clearance in G6PD deficiency due to defective NOX/p38 MAPK/AP-1 redox signaling,http://dx.doi.org/10.1016/j.redox.2019.101363,PMC6854078,31707353,CC BY-NC-ND,"Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway that modulates cellular redox homeostasis via the regeneration of NADPH. G6PD-deficient cells have a reduced ability to induce the innate immune response, thus increasing host susceptibility to pathogen infections. An important part of the immune response is the activation of the inflammasome. G6PD-deficient peripheral blood mononuclear cells (PBMCs) from patients and human monocytic (THP-1) cells were used as models to investigate whether G6PD modulates inflammasome activation. A decreased expression of IL-1β was observed in both G6PD-deficient PBMCs and PMA-primed G6PD-knockdown (G6PD-kd) THP-1 cells upon lipopolysaccharide (LPS)/adenosine triphosphate (ATP) or LPS/nigericin stimulation. The pro-IL-1β expression of THP-1 cells was decreased by G6PD knockdown at the transcriptional and translational levels in an investigation of the expression of the inflammasome subunits. The phosphorylation of p38 MAPK and downstream c-Fos expression were decreased upon G6PD knockdown, accompanied by decreased AP-1 translocation into the nucleus. Impaired inflammasome activation in G6PD-kd THP-1 cells was mediated by a decrease in the production of reactive oxygen species (ROS) by NOX signaling, while treatment with hydrogen peroxide (H(2)O(2)) enhanced inflammasome activation in G6PD-kd THP-1 cells. G6PD knockdown decreased Staphylococcus aureus and Escherichia coli clearance in G6PD-kd THP-1 cells and G6PD-deficient PBMCs following inflammasome activation. These findings support the notion that enhanced pathogen susceptibility in G6PD deficiency is, in part, due to an altered redox signaling, which adversely affects inflammasome activation and the bactericidal response.",2019 Nov 2,"['Yen, Wei-Chen', 'Wu, Yi-Hsuan', 'Wu, Chih-Ching', 'Lin, Hsin-Ru', 'Stern, Arnold', 'Chen, Shih-Hsiang', 'Shu, Jwu-Ching', 'Tsun-Yee Chiu, Daniel']",Redox Biol,,,False
f6e985e472df7bba7a7ef1568336c0443b919639,PMC,On the stability of sequences inserted into viral genomes,http://dx.doi.org/10.1093/ve/vez045,PMC6855363,31741748,CC BY-NC,"Viruses are widely used as vectors for heterologous gene expression in cultured cells or natural hosts, and therefore a large number of viruses with exogenous sequences inserted into their genomes have been engineered. Many of these engineered viruses are viable and express heterologous proteins at high levels, but the inserted sequences often prove to be unstable over time and are rapidly lost, limiting heterologous protein expression. Although virologists are aware that inserted sequences can be unstable, processes leading to insert instability are rarely considered from an evolutionary perspective. Here, we review experimental work on the stability of inserted sequences over a broad range of viruses, and we present some theoretical considerations concerning insert stability. Different virus genome organizations strongly impact insert stability, and factors such as the position of insertion can have a strong effect. In addition, we argue that insert stability not only depends on the characteristics of a particular genome, but that it will also depend on the host environment and the demography of a virus population. The interplay between all factors affecting stability is complex, which makes it challenging to develop a general model to predict the stability of genomic insertions. We highlight key questions and future directions, finding that insert stability is a surprisingly complex problem and that there is need for mechanism-based, predictive models. Combining theoretical models with experimental tests for stability under varying conditions can lead to improved engineering of viral modified genomes, which is a valuable tool for understanding genome evolution as well as for biotechnological applications, such as gene therapy.",2019 Nov 14,"['Willemsen, Anouk', 'Zwart, Mark P']",Virus Evol,,,True
62219dc0553022e4faac2b1523e7e0a2d1eaec30,PMC,Analysis of mortality prognostic factors using model for end-stage liver disease with incorporation of serum-sodium classification for liver cirrhosis complications: A retrospective cohort study,http://dx.doi.org/10.1097/MD.0000000000017862,PMC6855481,31702650,CC BY-NC,"Since the progression of cirrhosis is accelerated each time a complication recurs, the management and treatment of the complication is critical in enhancement of the quality of life and expectation of life in patients. The use of model for end-stage liver disease with incorporation of serum-sodium (MELD-Na) with physiological indicators can be used to assess severity and differentiate therapeutic interventions. This study is aimed to determine the mean survival period and cumulative survival rate by classifying patients into high-risk and low-risk groups based on MELD-Na, a predictor of mortality in liver disease, and to investigate the mortality prognostic factors. A retrospective cohort study, which follows the STROBE checklist, was performed. 263 patients who were diagnosed with liver cirrhosis complications for the first time and hospitalized were selected as the subjects of this study. The collected data were analyzed based on the survival package provided by the statistical program R version 3.4.2. Subjects were classified into high-risk and low-risk groups using MELD-Na 14 points where sensitivity and specificity crossed the cut-off point. Gender, age, and primary caregiver were significant variables in the mortality high-risk group, and AST, albumin, and primary caregiver were significant variables in the mortality low-risk group. Based on these mortality prognostic factors, it is possible to present the factors affecting mortality in patients who were diagnosed with liver cirrhosis complications for the first time. The classification of patients by risk level could be the foundation to provide accurate guidelines for management and it is necessary to modify prognostic factors and apply nursing interventions to manage complications.",2019 Nov 11,"['Kim, Yuna', 'Kim, Kyunghee', 'Jang, Insil']",Medicine (Baltimore),,,True
d279bf13512bd679f95fc43b64aa11b3eac47ded,PMC,Mental well-being of international migrants to Japan: a systematic review,http://dx.doi.org/10.1136/bmjopen-2019-029988,PMC6858191,31685498,CC BY-NC,"BACKGROUND: Migration is a stressful process of resettlement and acculturation that can often negatively impact the mental health of migrants. International migration to Japan, a country with dominant ethnic homogeneity, is growing steadily amid an ageing domestic population and severe labour shortages. OBJECTIVES: To identify the contemporary barriers to, and facilitators of, mental well-being among the migrant population in Japan. DESIGN: Systematic review DATA SOURCES: PubMed, ProQuest, Web of Science, Ichushi and J-Stage ELIGIBILITY CRITERIA: Research articles examining the mental well-being of international migrants in Japan that were published in English or Japanese between January 2000 and September 2018 were included. DATA EXTRACTION AND SYNTHESIS: Full texts of relevant articles were screened and references of the included studies were hand-searched for further admissible articles. Study characteristics, mental well-being facilitators and barriers, as well as policy recommendations were synthesised into categorical observations and were then thematically analysed. RESULTS: Fifty-five studies (23 published in English), surveying a total of 8649 migrants, were identified. The most commonly studied migrant nationalities were Brazilian (36%), followed by Chinese (27%) and Filipino (8%). Thematic analysis of barriers to mental well-being among migrants chiefly identified ‘language difficulties’, ‘being female’ and ‘lack of social support’, whereas the primary facilitators were ‘social networks’ followed by ‘cultural identity’. Policy recommendations for authorities generally described more migrant support services and cross-cultural awareness among the Japanese public. CONCLUSION: Access to social support networks of various types appears to be an influential factor affecting the mental well-being of international migrants in Japan. More research is necessary on how to promote such connections to foster a more inclusive and multicultural Japanese society amid rapid demographic change. PROSPERO REGISTRATION NUMBER: CRD42018108421.",2019 Nov 3,"['Miller, Russell', 'Tomita, Yuri', 'Ong, Ken Ing Cherng', 'Shibanuma, Akira', 'Jimba, Masamine']",BMJ Open,,,True
e546b975c39f4fd2c5c35fb0320cacc3ded2adac,PMC,Mental well-being of international migrants to Japan: a systematic review,http://dx.doi.org/10.1136/bmjopen-2019-029988,PMC6858191,31685498,CC BY-NC,"BACKGROUND: Migration is a stressful process of resettlement and acculturation that can often negatively impact the mental health of migrants. International migration to Japan, a country with dominant ethnic homogeneity, is growing steadily amid an ageing domestic population and severe labour shortages. OBJECTIVES: To identify the contemporary barriers to, and facilitators of, mental well-being among the migrant population in Japan. DESIGN: Systematic review DATA SOURCES: PubMed, ProQuest, Web of Science, Ichushi and J-Stage ELIGIBILITY CRITERIA: Research articles examining the mental well-being of international migrants in Japan that were published in English or Japanese between January 2000 and September 2018 were included. DATA EXTRACTION AND SYNTHESIS: Full texts of relevant articles were screened and references of the included studies were hand-searched for further admissible articles. Study characteristics, mental well-being facilitators and barriers, as well as policy recommendations were synthesised into categorical observations and were then thematically analysed. RESULTS: Fifty-five studies (23 published in English), surveying a total of 8649 migrants, were identified. The most commonly studied migrant nationalities were Brazilian (36%), followed by Chinese (27%) and Filipino (8%). Thematic analysis of barriers to mental well-being among migrants chiefly identified ‘language difficulties’, ‘being female’ and ‘lack of social support’, whereas the primary facilitators were ‘social networks’ followed by ‘cultural identity’. Policy recommendations for authorities generally described more migrant support services and cross-cultural awareness among the Japanese public. CONCLUSION: Access to social support networks of various types appears to be an influential factor affecting the mental well-being of international migrants in Japan. More research is necessary on how to promote such connections to foster a more inclusive and multicultural Japanese society amid rapid demographic change. PROSPERO REGISTRATION NUMBER: CRD42018108421.",2019 Nov 3,"['Miller, Russell', 'Tomita, Yuri', 'Ong, Ken Ing Cherng', 'Shibanuma, Akira', 'Jimba, Masamine']",BMJ Open,,,True
5cec667baa25d7a4f00c997f16feb8846f8b95f0,PMC,Mental well-being of international migrants to Japan: a systematic review,http://dx.doi.org/10.1136/bmjopen-2019-029988,PMC6858191,31685498,CC BY-NC,"BACKGROUND: Migration is a stressful process of resettlement and acculturation that can often negatively impact the mental health of migrants. International migration to Japan, a country with dominant ethnic homogeneity, is growing steadily amid an ageing domestic population and severe labour shortages. OBJECTIVES: To identify the contemporary barriers to, and facilitators of, mental well-being among the migrant population in Japan. DESIGN: Systematic review DATA SOURCES: PubMed, ProQuest, Web of Science, Ichushi and J-Stage ELIGIBILITY CRITERIA: Research articles examining the mental well-being of international migrants in Japan that were published in English or Japanese between January 2000 and September 2018 were included. DATA EXTRACTION AND SYNTHESIS: Full texts of relevant articles were screened and references of the included studies were hand-searched for further admissible articles. Study characteristics, mental well-being facilitators and barriers, as well as policy recommendations were synthesised into categorical observations and were then thematically analysed. RESULTS: Fifty-five studies (23 published in English), surveying a total of 8649 migrants, were identified. The most commonly studied migrant nationalities were Brazilian (36%), followed by Chinese (27%) and Filipino (8%). Thematic analysis of barriers to mental well-being among migrants chiefly identified ‘language difficulties’, ‘being female’ and ‘lack of social support’, whereas the primary facilitators were ‘social networks’ followed by ‘cultural identity’. Policy recommendations for authorities generally described more migrant support services and cross-cultural awareness among the Japanese public. CONCLUSION: Access to social support networks of various types appears to be an influential factor affecting the mental well-being of international migrants in Japan. More research is necessary on how to promote such connections to foster a more inclusive and multicultural Japanese society amid rapid demographic change. PROSPERO REGISTRATION NUMBER: CRD42018108421.",2019 Nov 3,"['Miller, Russell', 'Tomita, Yuri', 'Ong, Ken Ing Cherng', 'Shibanuma, Akira', 'Jimba, Masamine']",BMJ Open,,,False
789679b6d2b9b81d978d080a3470cbff850ac835,PMC,Mental well-being of international migrants to Japan: a systematic review,http://dx.doi.org/10.1136/bmjopen-2019-029988,PMC6858191,31685498,CC BY-NC,"BACKGROUND: Migration is a stressful process of resettlement and acculturation that can often negatively impact the mental health of migrants. International migration to Japan, a country with dominant ethnic homogeneity, is growing steadily amid an ageing domestic population and severe labour shortages. OBJECTIVES: To identify the contemporary barriers to, and facilitators of, mental well-being among the migrant population in Japan. DESIGN: Systematic review DATA SOURCES: PubMed, ProQuest, Web of Science, Ichushi and J-Stage ELIGIBILITY CRITERIA: Research articles examining the mental well-being of international migrants in Japan that were published in English or Japanese between January 2000 and September 2018 were included. DATA EXTRACTION AND SYNTHESIS: Full texts of relevant articles were screened and references of the included studies were hand-searched for further admissible articles. Study characteristics, mental well-being facilitators and barriers, as well as policy recommendations were synthesised into categorical observations and were then thematically analysed. RESULTS: Fifty-five studies (23 published in English), surveying a total of 8649 migrants, were identified. The most commonly studied migrant nationalities were Brazilian (36%), followed by Chinese (27%) and Filipino (8%). Thematic analysis of barriers to mental well-being among migrants chiefly identified ‘language difficulties’, ‘being female’ and ‘lack of social support’, whereas the primary facilitators were ‘social networks’ followed by ‘cultural identity’. Policy recommendations for authorities generally described more migrant support services and cross-cultural awareness among the Japanese public. CONCLUSION: Access to social support networks of various types appears to be an influential factor affecting the mental well-being of international migrants in Japan. More research is necessary on how to promote such connections to foster a more inclusive and multicultural Japanese society amid rapid demographic change. PROSPERO REGISTRATION NUMBER: CRD42018108421.",2019 Nov 3,"['Miller, Russell', 'Tomita, Yuri', 'Ong, Ken Ing Cherng', 'Shibanuma, Akira', 'Jimba, Masamine']",BMJ Open,,,False
5f744537090352fd5997270dc07700a60dee0139,PMC,Mental well-being of international migrants to Japan: a systematic review,http://dx.doi.org/10.1136/bmjopen-2019-029988,PMC6858191,31685498,CC BY-NC,"BACKGROUND: Migration is a stressful process of resettlement and acculturation that can often negatively impact the mental health of migrants. International migration to Japan, a country with dominant ethnic homogeneity, is growing steadily amid an ageing domestic population and severe labour shortages. OBJECTIVES: To identify the contemporary barriers to, and facilitators of, mental well-being among the migrant population in Japan. DESIGN: Systematic review DATA SOURCES: PubMed, ProQuest, Web of Science, Ichushi and J-Stage ELIGIBILITY CRITERIA: Research articles examining the mental well-being of international migrants in Japan that were published in English or Japanese between January 2000 and September 2018 were included. DATA EXTRACTION AND SYNTHESIS: Full texts of relevant articles were screened and references of the included studies were hand-searched for further admissible articles. Study characteristics, mental well-being facilitators and barriers, as well as policy recommendations were synthesised into categorical observations and were then thematically analysed. RESULTS: Fifty-five studies (23 published in English), surveying a total of 8649 migrants, were identified. The most commonly studied migrant nationalities were Brazilian (36%), followed by Chinese (27%) and Filipino (8%). Thematic analysis of barriers to mental well-being among migrants chiefly identified ‘language difficulties’, ‘being female’ and ‘lack of social support’, whereas the primary facilitators were ‘social networks’ followed by ‘cultural identity’. Policy recommendations for authorities generally described more migrant support services and cross-cultural awareness among the Japanese public. CONCLUSION: Access to social support networks of various types appears to be an influential factor affecting the mental well-being of international migrants in Japan. More research is necessary on how to promote such connections to foster a more inclusive and multicultural Japanese society amid rapid demographic change. PROSPERO REGISTRATION NUMBER: CRD42018108421.",2019 Nov 3,"['Miller, Russell', 'Tomita, Yuri', 'Ong, Ken Ing Cherng', 'Shibanuma, Akira', 'Jimba, Masamine']",BMJ Open,,,False
1a15f074b28cbfa5bb3c38b708117f2b7d85c5c2,PMC,Mental well-being of international migrants to Japan: a systematic review,http://dx.doi.org/10.1136/bmjopen-2019-029988,PMC6858191,31685498,CC BY-NC,"BACKGROUND: Migration is a stressful process of resettlement and acculturation that can often negatively impact the mental health of migrants. International migration to Japan, a country with dominant ethnic homogeneity, is growing steadily amid an ageing domestic population and severe labour shortages. OBJECTIVES: To identify the contemporary barriers to, and facilitators of, mental well-being among the migrant population in Japan. DESIGN: Systematic review DATA SOURCES: PubMed, ProQuest, Web of Science, Ichushi and J-Stage ELIGIBILITY CRITERIA: Research articles examining the mental well-being of international migrants in Japan that were published in English or Japanese between January 2000 and September 2018 were included. DATA EXTRACTION AND SYNTHESIS: Full texts of relevant articles were screened and references of the included studies were hand-searched for further admissible articles. Study characteristics, mental well-being facilitators and barriers, as well as policy recommendations were synthesised into categorical observations and were then thematically analysed. RESULTS: Fifty-five studies (23 published in English), surveying a total of 8649 migrants, were identified. The most commonly studied migrant nationalities were Brazilian (36%), followed by Chinese (27%) and Filipino (8%). Thematic analysis of barriers to mental well-being among migrants chiefly identified ‘language difficulties’, ‘being female’ and ‘lack of social support’, whereas the primary facilitators were ‘social networks’ followed by ‘cultural identity’. Policy recommendations for authorities generally described more migrant support services and cross-cultural awareness among the Japanese public. CONCLUSION: Access to social support networks of various types appears to be an influential factor affecting the mental well-being of international migrants in Japan. More research is necessary on how to promote such connections to foster a more inclusive and multicultural Japanese society amid rapid demographic change. PROSPERO REGISTRATION NUMBER: CRD42018108421.",2019 Nov 3,"['Miller, Russell', 'Tomita, Yuri', 'Ong, Ken Ing Cherng', 'Shibanuma, Akira', 'Jimba, Masamine']",BMJ Open,,,False
f709c57759c73d92079f99c26fade99a13384f78,PMC,Comparison Of Four Anti-Avian IgY Secondary Antibodies Used In Western Blot And Dot-Blot ELISA To Detect Avian Bornavirus Antibodies In Four Different Bird Species,http://dx.doi.org/10.2147/VMRR.S227616,PMC6858837,31815098,CC BY-NC,"PURPOSE: This study evaluated the specificity of different avian secondary antibodies used in Western blot and dot-blot ELISA to detect avian bornavirus antibodies in bird plasma. METHODS: Plasma samples were collected from: two Blue and gold macaws, one positive and one negative for avian bornavirus by RT-PCR; a Cockatiel and a Monk parakeet prior to and following experimental infection; and, two Mallards, one positive and one negative for avian bornavirus by RT-PCR Samples were analyzed by Western blot and dot-blot ELISA that incorporated recombinant avian bornavirus nucleoprotein as the target analyte. Four species-specific anti-IgY secondary antibodies were used in the assays: goat anti-macaw IgY, goat anti-bird IgY, goat anti-duck IgY, and rabbit anti-chicken IgY. RESULTS: In the Western blot, anti-macaw IgY secondary antibody produced strong signals with Blue and gold macaw and Cockatiel positive plasma, but no signal with Mallard positive plasma. Anti-bird IgY secondary antibody produced strong signals with Blue and gold macaw, Cockatiel, and Mallard positive plasma. Anti-duck and anti-chicken IgY secondary antibody produced a strong and moderate signal, respectively, only with Mallard positive plasma. In the dot-blot ELISA, there was a distinct and significant difference (P<0.05) in the signal intensity between the different secondary antibodies within a bird species. Anti-macaw IgY secondary antibody produced significantly (P<0.05) stronger signals than the other secondary antibodies in Blue and gold macaw, Cockatiel, and Monk parakeet positive plasma, while anti-duck IgY secondary antibody produced significantly (P<0.05) stronger signals than the other secondary antibodies in Mallard positive plasma. CONCLUSION: In testing psittacines with immunoassays, and especially in assays that incorporate short incubation reaction times such as a dot-blot ELISA, species-specific anti-IgY secondary antibodies provided more accurate results.",2019 Nov 12,"['Escandon, Paulina', 'Heatley, J Jill', 'Berghman, Luc R', 'Tizard, Ian', 'Musser, Jeffrey MB']",Vet Med (Auckl),,,True
285423e1a13bb2e1b98795cc6bb0cb6f54c0f8fd,PMC,Lay media reporting of monkeypox in Nigeria,http://dx.doi.org/10.1136/bmjgh-2019-002019,PMC6861118,31799006,CC BY-NC,,2019 Nov 12,"['Oyebanji, Oyeronke', 'Ofonagoro, Ugonna', 'Akande, Oluwatosin', 'Nsofor, Ifeanyi', 'Ukenedo, Chika', 'Mohammed, Tarik Benjamin', 'Anueyiagu, Chimezie', 'Agenyi, Jeremiah', 'Yinka-Ogunleye, Adesola', 'Ihekweazu, Chikwe']",BMJ Glob Health,,,True
b66f94ce35f66aa3ce423a16a7e6c814966786d2,PMC,Feline coronavirus isolates from a part of Brazil: insights into molecular epidemiology and phylogeny inferred from the 7b gene,http://dx.doi.org/10.1292/jvms.19-0090,PMC6863716,31447457,CC BY-NC-ND,"The Feline coronavirus (FCoV) can lead to Feline infectious peritonitis (FIP), which the precise cause is still unknown. The theory of internal mutation suggests that a less virulent biotype of FCoV (FECV) would lead to another more pathogenic biotype (FIPV) capable of causing FIP. In this work, the 7b gene was amplified from 51 domestic cat plasma samples by semi-nested PCR and tested through phylogenetic and phylogeographical approaches. The 7b gene of Brazilian isolates displayed high conservation, a strong correlation between the geographic origin of the viral isolates and their genealogy, and its evolution was possibly shaped by a combination of high rates of nucleotide substitution and purifying selection.",2019 Oct 23,"['MYRRHA, Luciana Wanderley', 'SILVA, Fernanda Miquelitto Figueira', 'VIDIGAL, Pedro Marcus Pereira', 'RESENDE, Maurício', 'BRESSAN, Gustavo Costa', 'FIETTO, Juliana Lopes Rangel', 'SANTOS, Marcus Rebouças', 'SILVA, Laura Morais Nascimento', 'ASSAO, Viviane Sisdelli', 'SILVA-JÚNIOR, Abelardo', 'de ALMEIDA, Márcia Rogéria']",J Vet Med Sci,,,True
39244c86324ed37f0b32222540efeefd2144d458,PMC,Porcine IL-12 plasmid as an adjuvant improves the cellular and humoral immune responses of DNA vaccine targeting transmissible gastroenteritis virus spike gene in a mouse model,http://dx.doi.org/10.1292/jvms.18-0682,PMC6863717,31474664,CC BY-NC-ND,"Transmissible gastroenteritis (TGE), caused by transmissible gastroenteritis virus (TGEV), is a highly infectious disease in pigs. Vaccination is an effective approach to prevent TGEV infection. Here, we evaluated the potential of TGEV S1 as a DNA vaccine and porcine interleukin (pIL)-12 as an adjuvant in a mouse model. A DNA vaccine was constructed with the TGEV S1 gene to induce immune response in an experimental mouse model; pIL-12 was chosen as the immunological adjuvant within this DNA vaccine. The pVAX1-(TGEV-S1) and pVAX1-(pIL-12) vectors were transfected into BHK-21 cells and expressed in vitro. Experimental mice were separately immunized with each of the recombinant plasmids and controls through the intramuscular route. The lymphocytes isolated from the blood and spleen were analyzed for proliferation, cytotoxic activities, and populations of CD4(+) and CD8(+) cells. The titers of TGEV S1 in an enzyme-linked immunosorbent assay (ELISA) and TGEV neutralizing antibodies and the concentrations of interferon (IFN)-γ and IL-4 were also analyzed in the serum. The plasmids pVAX1-(TGEV-S1) and pVAX1-(pIL-12) could be expressed in BHK-21 cells, and the combination of pVAX1-(TGEV-S1) and pVAX1-(pIL-12) could induce a significant increase in all markers. pIL-12 could act as an immunological adjuvant in the DNA vaccine for TGEV-S1. Furthermore, the DNA vaccine prepared using TGEV-S1 and porcine IL-12 could induce excellent humoral and cellular immune responses.",2019 Oct 2,"['LI, Xunliang', 'LI, Pengchong', 'CAO, Liyan', 'BAI, Yunyun', 'CHEN, Huijie', 'LIU, He', 'REN, Xiaofeng', 'LI, Guangxing']",J Vet Med Sci,,,True
a93ae58385828b5de96f52d447e0305af7dbfe80,PMC,Artificial Blood: A Futuristic Dimension of Modern Day Transfusion 
Sciences,http://dx.doi.org/10.2174/1871525717666190617120045,PMC6864588,31204626,CC BY-NC,"Artificial blood is an innovative concept of transfusion medicine where specifically designed compounds perform the task of transport and delivery of oxygen in the body to replace this function of allogenic human blood transfusion. Several molecules have been developed in the past few decades to achieve this objective and continous refinements are being continuously made in the quest of the ideal blood substitute. Currently, available technology manufactures artificial blood from haemoglobin obtained from outdated human/bovine blood (Haemoglobin Based Oxygen Carriers) or utilizing Perfluorocarbons. These synthetic blood substitutes are advantageous in that they do not require compatibility testing, are free from blood borne infections, have prolonged shelf life and do not require refrigeration. Artificial blood is projected to have a significant impact on the development of medical care in the future. It can complement the current blood products for transfusion and create a stable supply of safe and effective products. It is likely to reduce the requirements of blood transfusions drastically especially in settings of trauma and surgery thereby reducing the reliance on banked donated blood.",2019 May,"['Haldar, Rudrashish', 'Gupta, Devendra', 'Chitranshi, Shweta', 'Singh, Manish Kumar', 'Sachan, Sumit']",Cardiovasc Hematol Agents Med Chem,,,True
ce6717ad3bb0da86077a5cbb8111576ea8230b2c,PMC,"Atti del 52° Congresso Nazionale: Società Italiana di Igiene, Medicina Preventiva e Sanità Pubblica (SItI)",http://dx.doi.org/10.15167/2421-4248/jpmh2019.60.3s1,PMC6865078,31777763,CC BY-NC,,2019 Oct 15,,J Prev Med Hyg,,,True
faec4bca24cb275ebc6c55e7cba3bd6a3b74df32,PMC,Expression and role of HEPIS in breast cancer,http://dx.doi.org/10.3892/ol.2019.10993,PMC6865829,31788121,CC BY-NC-ND,"Human embryo lung cellular protein interacting with severe acute respiratory syndrome-coronavirus nonstructural protein-10 (HEPIS) is expressed at varying levels in multiple organs and breast cancer cell lines. However, its expression and function in breast cancer cells has yet to be studied. Therefore, RNA in situ hybridization was used to detect the expression of HEPIS in breast cancer and cancer-adjacent normal breast tissue. HEPIS was expressed at lower levels in breast cancer compared with that in adjacent normal tissue. Subcellular localization of HEPIS was mainly found in the cytoplasm of HeLa cells. Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine cell proliferation assays were used to investigate the role of HEPIS in cancer cell proliferation. Ectopic expression of HEPIS in MCF-7 cells was found to significantly inhibit cell proliferation. In contrast, knockdown of HEPIS by RNA interference exhibited the opposite effect. Furthermore, a dual-luciferase reporter assay was performed and HEPIS overexpression specifically inhibited the activity of the NF-κB reporter gene. Results of the gene chip assay revealed that 2,231 genes were differentially expressed in HEPIS-overexpressing cells. Results of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that these genes were enriched in the ‘mitogen-activated protein kinase signaling pathway’, ‘JAK-STAT signaling pathway’ and ‘focal adhesion’. Reverse transcription-quantitative PCR was used to confirm the expression levels of the differentially expressed genes interleukin 2 receptor subunit α (IL2RA), interferon α and β receptor subunit 2 (IFNAR2) and IFα8 (IFNA8). In conclusion, the results of the present study indicated that HEPIS may function as a potential repressor of breast cancer.",2019 Dec 17,"['Hu, Fen', 'Zhang, Yunfeng', 'Li, Mi', 'Bai, Yun', 'Zhang, Xiujun']",Oncol Lett,,,True
319b8c97174d684a0e0f50dff4ecfdab294d2a05,PMC,Vaccine or field strains: the jigsaw pattern of infectious bronchitis virus molecular epidemiology in Poland,http://dx.doi.org/10.3382/ps/pez473,PMC6870560,31399745,CC BY-NC,"Infectious bronchitis (IB), caused by infectious bronchitis virus (IBV), account for severe economic losses in the poultry industry. The continuous emergence of a multitude of IBV variants poses many challenges for its diagnosis and control, and live attenuated vaccines, despite their routine use, still plays a significant role in driving IBV evolution, further complicating the epidemiological scenario. Unfortunately, the impact of different vaccination strategies on IB control, epidemiology, and diagnosis has rarely been investigated. This work presents the results of a large-scale diagnostic survey performed in Poland to study IBV molecular epidemiology and how vaccination may affect the viral circulation in the field. To this purpose, 589 samples were collected between May 2017 and January 2019, tested by reverse transcription-PCR for IBV and sequenced. Vaccine and field strains were discriminated based on genetic and anamnestic information. The most commonly detected lineages were 793B (79%) and variant 2 (17.4%), with sporadic detections of QX, Mass, and D274-like strains. Most of the detected strains had a vaccine origin: 46.3% matched one of the applied vaccines, while 36.5% were genetically related to vaccines not implemented in the respective protocol. Besides their practical value for the proper planning of vaccination protocols in Poland, these results suggest that only a fraction (17.2%) of the circulating strains are field ones, imposing a careful assessment of the actual IBV field menaces. Moreover, phenomena like vaccine spreading and persistence seem to occur commonly, stressing the need to further study the epidemiological consequences of the extensive use of live vaccines.",2019 Dec 9,"['Legnardi, Matteo', 'Franzo, Giovanni', 'Koutoulis, Konstantinos C', 'Wiśniewski, Marek', 'Catelli, Elena', 'Tucciarone, Claudia Maria', 'Cecchinato, Mattia']",Poult Sci,,,True
f22bbd33c610d6ee6e4f8fe91e346bd8d114b0d6,PMC,The socio-economic distribution of exposure to Ebola: Survey evidence from Liberia and Sierra Leone,http://dx.doi.org/10.1016/j.ssmph.2019.100472,PMC6880008,31788533,CC BY-NC-ND,"Socio-economic factors are widely believed to have been an important driver of the transmission of Ebola Virus Disease (EVD) during the West African outbreak of 2014–16, however, studies that have investigated the relationship between socio-economic status (SES) and EVD have found inconsistent results. Using nationally representative household survey data on whether respondents knew a close friend or family member with Ebola, we explore the SES determinants of EVD exposure along individual, household, and community lines in Liberia and Sierra Leone. While we find no overall association between household wealth and EVD exposure, we find that pooled data mask important differences observed within countries with higher wealth households more likely to have been exposed to EVD in Sierra Leone and the opposite relationship in Liberia. Finally, we also generally find a positive association between education and EVD exposure both at the individual and the community levels in the full sample. There is an urgent need to better understand these relationships to examine both why the outbreak spread and to help prepare for future outbreaks.",2019 Nov 15,"['Grépin, Karen A.', 'Poirier, Mathieu J.P.', 'Fox, Ashley M.']",SSM Popul Health,,,False
d4ae876b5fb0b3c64650915ca3970c0a58d6433c,PMC,Why Are Children With Bronchiolitis At Risk Of Urinary Tract Infections?,http://dx.doi.org/10.2147/RMHP.S222470,PMC6881700,31819685,CC BY-NC,"Viral respiratory infections are frequently eliminated from human bodies without any sequelae. Secondary serious bacterial infection (SBI) in children with acute bronchiolitis has been an apprehension expressed by health care providers. Several published studies have shown an association between acute bronchiolitis and secondary bacterial infection, including urinary tract infections (UTI). However, the proposed mechanism by which a virus can induce UTIs is not yet known. The aim of this commentary is to update the current evidence of risk of UTI in children with bronchiolitis. We present several clinical studies related to the topic as well as a brief review of the potential pathophysiology of secondary infections that could present with viral respiratory illness.",2019 Nov 14,"Hendaus, Mohamed A",Risk Manag Healthc Policy,,,True
57f7bd687c1b968f782d3a1aa7f7fd051acdcaee,PMC,Inhibition of SARS-CoV 3CL protease by flavonoids,http://dx.doi.org/10.1080/14756366.2019.1690480,PMC6882434,31724441,CC BY-NC,"There were severe panics caused by Severe Acute Respiratory Syndrome (SARS) and Middle-East Respiratory Syndrome-Coronavirus. Therefore, researches targeting these viruses have been required. Coronaviruses (CoVs) have been rising targets of some flavonoids. The antiviral activity of some flavonoids against CoVs is presumed directly caused by inhibiting 3C-like protease (3CLpro). Here, we applied a flavonoid library to systematically probe inhibitory compounds against SARS-CoV 3CLpro. Herbacetin, rhoifolin and pectolinarin were found to efficiently block the enzymatic activity of SARS-CoV 3CLpro. The interaction of the three flavonoids was confirmed using a tryptophan-based fluorescence method, too. An induced-fit docking analysis indicated that S1, S2 and S3′ sites are involved in binding with flavonoids. The comparison with previous studies showed that Triton X-100 played a critical role in objecting false positive or overestimated inhibitory activity of flavonoids. With the systematic analysis, the three flavonoids are suggested to be templates to design functionally improved inhibitors.",2019 Nov 14,"['Jo, Seri', 'Kim, Suwon', 'Shin, Dong Hae', 'Kim, Mi-Sun']",J Enzyme Inhib Med Chem,,,True
983df610328c1e73e3c12546d42a14d520844f9b,PMC,Seroprevalence of major avian respiratory diseases in broiler and sonali chicken in selected areas of Bangladesh,http://dx.doi.org/10.5455/javar.2019.f383,PMC6882717,31819887,CC BY-NC,"OBJECTIVE: This study was conducted to investigate different respiratory diseases in broiler and sonali birds in some selected districts of Bangladesh. MATERIALS AND METHODS: We were collected a total of 460 blood samples from 46 farms with 36 broiler farms and 10 sonali farms (cross-breed) from 2015 to 2017. All the collected serum samples were tested for determining specific antibodies of avian rhinotracheitis (ART) virus, infectious laryngotracheitis (ILT) virus, infectious bronchitis (IBV) virus, and Ornithobacterium rhinotracheale (ORT) infection using commercially available enzyme-linked immunosorbent assay kits. RESULTS: The overall seropositivity was highest in ORT (45.9%), followed by IBV (37.6%), ART (2.6%), and ILT (0.4%). Out of 360 broiler samples, highest seropositivity was recorded in ORT (43.3%) and lowest in IBV (31.4%). Surprisingly, no broiler samples were found positive for ART and ILT. In case of sonali, the seropositivity was highest in IBV (60%) and lowest in ILT (2%). With respect to types of birds and age groups, the seropositive percentage of all four pathogens was found higher in sonali than broiler. Between two age groups of sonali, the seropositive percentage of ART (12%), ORT (55%), ILT (2%), and IBV (60%) was highest at 21–60 weeks of age compared to 5–20 weeks of age. However, based on location, the seropositive of ORT and IBV was highest in Jamalpur (63.3%) and Fulbariya and Trishal (50%) and lowest in Sreepur (16.7%) and Jamalpur (3.3%). CONCLUSION: The four pathogens are ubiquitous in nature for the sonali chickens, and the prevalence of ORT and IBV was the most prevalent viruses in the study areas. This study indicates a need for improved surveillance and characterization of ORT and ART circulating in all types of poultry in Bangladesh.",2019 Nov 3,"['Bhuiyan, Zafar Ahmed', 'Ali, Md Zulfekar', 'Moula, Mohammad Moktader', 'Bary, Md Akramul', 'Arefin, Nishat', 'Giasuddin, Md', 'Khan, Zahed Uddin Mahmood']",J Adv Vet Anim Res,,,True
595ec9383d19b691e17362abb472fa1103074014,PMC,"Enhancement of antigen-specific humoral immune responses and protein solubility through conjugation of bacterial flagellin, Vibrio vulnificus FlaB, to the N-terminus of porcine epidemic diarrhea virus surface protein antigen S0",http://dx.doi.org/10.4142/jvs.2019.20.e70,PMC6883195,31775197,CC BY-NC,"Porcine epidemic diarrhea (PED) is a highly contagious enteric swine disease. The large economic impact of PED on the swine industry worldwide has made the development of an effective PED vaccine a necessity. S0, a truncated region of the porcine epidemic diarrhea virus (PEDV) spike protein, has been suggested as a candidate antigen for PED subunit vaccines; however, poor solubility problems when the protein is expressed in Escherichia coli, and the inherent problems of subunit vaccines, such as low immunogenicity, remain. Flagellin has been widely used as a fusion partner to enhance the immunogenicity and solubility of many difficult-to-express proteins; however, the conjugation effect of flagellin varies depending on the target antigen or the position of the fusion placement. Here, we conjugated flagellin, Vibrio vulnificus FlaB, to the N- and C-termini of S0 and evaluated the ability of the fusion to enhance the solubility and immunogenicity of S0. Flagellin conjugation in the presence of the trigger factor chaperone tig greatly improved the solubility of the fusion protein (up to 99%) regardless of its conjugation position. Of importance, flagellin conjugated to the N-terminus of S0 significantly enhanced S0-specific humoral immune responses compared to other recombinant antigens in Balb/c mice. The mechanism of this phenomenon was investigated through in vitro and in vivo studies. These findings provide important information for the development of a novel PED vaccine and flagellin-based immunotherapeutics.",2019 Nov 5,"['Oh, Seo-ho', 'Kim Cho, Young-Saeng', 'Lee, Ho-Bin', 'Lee, Sang-Mok', 'Kim, Whee-Soo', 'Hong, Liang', 'Cho, Chong-Su', 'Choi, Yun-Jaie', 'Kang, Sang-Kee']",J Vet Sci,,,True
cac688a10fc20a83e2a43abc2297738c26b8afb4,PMC,Causative agents and epidemiology of diarrhea in Korean native calves,http://dx.doi.org/10.4142/jvs.2019.20.e64,PMC6883198,31775191,CC BY-NC,"Calf diarrhea caused by infectious agents is associated with economic losses in the cattle industry. The purpose of this study was to identify the causative agents and epidemiological characteristics of diarrhea in Korean native calves (KNC). In total, 207 diarrheal KNC aged less than 7 months were investigated. Fecal samples collected from the rectum were examined for causative agents using polymerase chain reaction (PCR) or real-time PCR and the number of oocysts were counted. Fourteen causative agents were detected from 164 of the 207 diarrheal KNC. Rotavirus was the most common agent (34.8%), followed by Eimeria spp. (31.7%), Escherichia coli (22.0%), Giardia spp. (14.0%), Clostridium difficile (9.8%), bovine viral diarrhea virus (8.5%), coronavirus (7.9%), Cryptosporidium spp. (7.3%), torovirus (6.7%), parvovirus (5.5%), norovirus (4.9%), kobuvirus (1.8%), adenovirus (1.2%), and Salmonella spp. (0.6%). About 95 (57.9%) of 164 calves were infected with a single causative agent and 42.1% were infected by multiple agents. No significant difference was observed in mortality between calves infected with a single agent and multiple agents. The occurrence of diarrhea caused by rotavirus, Eimeria spp., kobuvirus, and Giardia spp. was significantly different based on onset age, and the prevalence of diarrhea caused by rotavirus or C. difficile was significantly different between seasons. This study help the understanding of KNC diarrhea for the development of an effective strategy for disease prevention and control, especially in Eastern provinces of South Korea.",2019 Nov 25,"['Lee, Sung-Hwan', 'Kim, Ha-Young', 'Choi, Eun Wha', 'Kim, Doo']",J Vet Sci,,,True
f2948dc01fd28774bb06b6c6995bec2a2f466f2a,PMC,Household preparedness for emergency events: a cross-sectional survey on residents in four regions of China,http://dx.doi.org/10.1136/bmjopen-2019-032462,PMC6887017,31727663,CC BY-NC,"OBJECTIVE: This study aimed to assess household preparedness for emergency events and its determinants in China. DESIGN: A cross-sectional questionnaire survey was conducted on 3541 households in China in 2015. PARTICIPANTS: Households were selected using a stratified cluster sampling strategy, representing central, eastern, western and southern regions of China. The designed questionnaires were administered through face-to-face interviews. OUTCOME MEASURES: Household emergency preparedness was measured with 14 indicators, tapping into the supply of nine emergency necessities (food and water, extra batteries, battery-powered radio, battery-operated torch, first-aid kit, gas mask, fire extinguisher, escape ropes, whistle), coverage of accident insurance, knowledge of local emergency response systems (emergency numbers, exit routes and shelters) and availability of a household evacuation plan. If an individual acted on 9 of the 14 indicators, they were deemed well prepared. Logistic regression models were established to identify predictors of well preparedness based on 3541 returned questionnaires containing no missing values. RESULTS: Only 9.9% of households were well prepared for emergencies: 53.6% did not know what to do and 31.6% did not want to think about it. A higher level of preparedness was found in the respondents who have attained higher education (adjusted OR=0.826 compared with the higher level), participated in emergency training activities (adjusted OR=2.299), had better emergency knowledge (adjusted OR=2.043), reported less fate-submissiveness (adjusted OR=1.385) and more self-reliance (adjusted OR=1.349), prior exposure to emergency events (adjusted OR=1.280) and held more positive attitudes towards preparedness (adjusted OR=1.286). CONCLUSION: Household preparedness for emergency events is poor in China. Lack of motivation, negative attitude to preparedness and knowledge shortfall are major but remediable barriers for household preparedness.",2019 Nov 14,"['Chen, Chao Yi', 'Xu, Wei', 'Dai, Yajun', 'Xu, Weilan', 'Liu, Chaojie', 'Wu, Qunhong', 'Gao, Lijun', 'Kang, Zheng', 'Hao, Yanhua', 'Ning, Ning']",BMJ Open,,,True
84ef152ba76ced39a6ab7f082895541c1b3ea9ec,PMC,Household preparedness for emergency events: a cross-sectional survey on residents in four regions of China,http://dx.doi.org/10.1136/bmjopen-2019-032462,PMC6887017,31727663,CC BY-NC,"OBJECTIVE: This study aimed to assess household preparedness for emergency events and its determinants in China. DESIGN: A cross-sectional questionnaire survey was conducted on 3541 households in China in 2015. PARTICIPANTS: Households were selected using a stratified cluster sampling strategy, representing central, eastern, western and southern regions of China. The designed questionnaires were administered through face-to-face interviews. OUTCOME MEASURES: Household emergency preparedness was measured with 14 indicators, tapping into the supply of nine emergency necessities (food and water, extra batteries, battery-powered radio, battery-operated torch, first-aid kit, gas mask, fire extinguisher, escape ropes, whistle), coverage of accident insurance, knowledge of local emergency response systems (emergency numbers, exit routes and shelters) and availability of a household evacuation plan. If an individual acted on 9 of the 14 indicators, they were deemed well prepared. Logistic regression models were established to identify predictors of well preparedness based on 3541 returned questionnaires containing no missing values. RESULTS: Only 9.9% of households were well prepared for emergencies: 53.6% did not know what to do and 31.6% did not want to think about it. A higher level of preparedness was found in the respondents who have attained higher education (adjusted OR=0.826 compared with the higher level), participated in emergency training activities (adjusted OR=2.299), had better emergency knowledge (adjusted OR=2.043), reported less fate-submissiveness (adjusted OR=1.385) and more self-reliance (adjusted OR=1.349), prior exposure to emergency events (adjusted OR=1.280) and held more positive attitudes towards preparedness (adjusted OR=1.286). CONCLUSION: Household preparedness for emergency events is poor in China. Lack of motivation, negative attitude to preparedness and knowledge shortfall are major but remediable barriers for household preparedness.",2019 Nov 14,"['Chen, Chao Yi', 'Xu, Wei', 'Dai, Yajun', 'Xu, Weilan', 'Liu, Chaojie', 'Wu, Qunhong', 'Gao, Lijun', 'Kang, Zheng', 'Hao, Yanhua', 'Ning, Ning']",BMJ Open,,,True
d0e4a23b392c97a4cce74b1da7bffffa6eee36ed,PMC,Household preparedness for emergency events: a cross-sectional survey on residents in four regions of China,http://dx.doi.org/10.1136/bmjopen-2019-032462,PMC6887017,31727663,CC BY-NC,"OBJECTIVE: This study aimed to assess household preparedness for emergency events and its determinants in China. DESIGN: A cross-sectional questionnaire survey was conducted on 3541 households in China in 2015. PARTICIPANTS: Households were selected using a stratified cluster sampling strategy, representing central, eastern, western and southern regions of China. The designed questionnaires were administered through face-to-face interviews. OUTCOME MEASURES: Household emergency preparedness was measured with 14 indicators, tapping into the supply of nine emergency necessities (food and water, extra batteries, battery-powered radio, battery-operated torch, first-aid kit, gas mask, fire extinguisher, escape ropes, whistle), coverage of accident insurance, knowledge of local emergency response systems (emergency numbers, exit routes and shelters) and availability of a household evacuation plan. If an individual acted on 9 of the 14 indicators, they were deemed well prepared. Logistic regression models were established to identify predictors of well preparedness based on 3541 returned questionnaires containing no missing values. RESULTS: Only 9.9% of households were well prepared for emergencies: 53.6% did not know what to do and 31.6% did not want to think about it. A higher level of preparedness was found in the respondents who have attained higher education (adjusted OR=0.826 compared with the higher level), participated in emergency training activities (adjusted OR=2.299), had better emergency knowledge (adjusted OR=2.043), reported less fate-submissiveness (adjusted OR=1.385) and more self-reliance (adjusted OR=1.349), prior exposure to emergency events (adjusted OR=1.280) and held more positive attitudes towards preparedness (adjusted OR=1.286). CONCLUSION: Household preparedness for emergency events is poor in China. Lack of motivation, negative attitude to preparedness and knowledge shortfall are major but remediable barriers for household preparedness.",2019 Nov 14,"['Chen, Chao Yi', 'Xu, Wei', 'Dai, Yajun', 'Xu, Weilan', 'Liu, Chaojie', 'Wu, Qunhong', 'Gao, Lijun', 'Kang, Zheng', 'Hao, Yanhua', 'Ning, Ning']",BMJ Open,,,True
a0ee437d7eab376084d070124b4070598480a179,PMC,Antidengue potential of leaf extracts of Pavetta tomentosa and Tarenna asiatica (Rubiaceae) against dengue virus and its vector Aedes aegypti (Diptera: Culicidae),http://dx.doi.org/10.1016/j.heliyon.2019.e02732,PMC6889234,31844692,CC BY-NC-ND,"The aim of the present study was to screen the anti-dengue potential of crude leaf extracts of two plants from Pavetta tomentosa and Tarenna asiatica. For larvicidal assay, the acetone extract of both plants showed maximum effects, with the least LC(50) and LC(90) values (P. tomentosa (5.968 and 7.493 μg/ml) and T. asiatica (1.288 and 1.992 μg/ml)) and the same extract of both plants exhibited better pupicidal potency. The adulticidal activity of both plants (0–60 min interval periods) recorded best results in acetone extracts and the LC(50) and LC(90) values were recorded as P. tomentosa (32.105 and 41.001 μg/ml) and T. asiatica (09.012 and 11.854 μg/ml). Among the two plants P. tomentosa acetone leaf extract have good antiviral property against Dengue viral cell line. In addition, the phytochemical nature of the plant reveals the presence of saponins, flavonoids and alkaloids in all the tested extracts of both plants. GC-MS analysis revealed Hexanedioic acid, Bis(2-Ethylhexyl) Ester (22.54) and 2,6,10,14,18,22- Tetracosahexane, 2,6,10, 15, 19,15,19,23- Hexamethyl-(ALL-E)- (25.33) identified as two major phytoconstitutents in P. tomentosa and Tetracontane (23.580) is a major compound identified from T. asiatica acetone extracts. The functional groups of chemical compounds (aromatis, alkanes, alkyls and carboxylic acids) from P. tomentosa and T. asiatica were analyzed by FT-IR spectrum.",2019 Nov 26,"['Pratheeba, T.', 'Taranath, V.', 'Sai Gopal, DVR', 'Natarajan, D.']",Heliyon,,,False
c64f469a3115f900053a2313679efdf81cb35741,PMC,Cross-sectional investigation and risk factor analysis of community-acquired and hospital-associated canine viral infectious respiratory disease complex,http://dx.doi.org/10.1016/j.heliyon.2019.e02726,PMC6895754,31844690,CC BY-NC-ND,"Canine infectious respiratory disease complex (CIRDC) is associated with multiple factors. The possible transmission source can be via community-acquired infection (CAI) or hospital-associated infection (HAI), but the variable factors within these two routes are not well described. This study aimed to (i) investigate a cross-sectional incidence of canine respiratory viruses, including influenza (CIV), parainfluenza, distemper (CDV), respiratory coronavirus (CRCoV), adenovirus-2, and herpesvirus, in respiratory-diseased dogs, and (ii) analyze the possibly related risk factors. In total 209 dogs with respiratory illness, consisting of 133 CAI and 76 HAI dogs, were studied. Both nasal and oropharyngeal swabs were sampled from each dog and subjected for CIRDC virus detection using multiplex PCRs. Common six viruses associated with CIRDC were detected in both groups with CIV and CRCoV being predominantly found. Only CDV was significantly more prevalent in CAI than HAI dogs. Multiple virus detections were found in 81.2% and 78.9% of CAI and HAI dogs, respectively. Co-detection of CIV and CRCoV was represented the highest proportion and most often found with other CIRD viruses. Moreover, the clinical severity level was notably related to the age of infected dogs, but not to the vaccination status, sex and transmission route. Since healthy or control dogs were not included in this study, the prevalence of the CIRD virus infections could not be assessed.",2019 Nov 14,"['Piewbang, Chutchai', 'Rungsipipat, Anudep', 'Poovorawan, Yong', 'Techangamsuwan, Somporn']",Heliyon,,,False
37894de51fed87b7b8b323f9ca56cdabdc164a94,PMC,Respiratory syncytial virus–associated illness in adults with advanced chronic obstructive pulmonary disease and/or congestive heart failure,http://dx.doi.org/10.1002/jmv.25285,PMC6900175,30132922,CC BY-NC,"BACKGROUND: Respiratory syncytial virus (RSV) is recognized as a serious pathogen in people with chronic cardiopulmonary conditions. Immunoprophylaxis might be considered for adults at high‐risk for frequent and severe RSV infection. Thus, we studied the incidence of RSV‐related medically attended acute respiratory illness (MARI) in adults with severe chronic obstructive pulmonary disease (COPD) and/or congestive heart failure (CHF). METHODS: Subjects ≥50 years of age with Gold Class III/IV COPD and/or American Heart Association class III/IV CHF and exposure to children ≥once per month were recruited. Subjects were evaluated over 1.5 to 2.5 years for RSV‐associated MARI, defined as polymerase chain reaction (PCR) and/or seroresponse. RESULTS: Four hundred forty‐five subjects were enrolled between October 2011 and May 2012. Overall, 99 RSV infections were documented by PCR or serology for a cumulative incidence of 22.2%. Of these, 42 (9.4%) subjects had protocol‐specified RSV‐MARI for an incidence of 4.68/100 patient‐seasons. All‐cause MARI was common (63.85/100 patient‐seasons) with rhinovirus most commonly identified. CONCLUSION: RSV infection was common in adults with severe COPD and/or advanced CHF. Given the severity of underlying cardiopulmonary diseases in the study population, most illnesses were surprisingly mild. Thus, active immunization rather than passive immunoprophylaxis with monoclonal antibodies may be a more cost‐effective strategy.",2019 Jan 24,"['Falsey, Ann R', 'Walsh, Edward E', 'Esser, Mark T', 'Shoemaker, Kathryn', 'Yu, Li', 'Griffin, M Pam']",J Med Virol,,,True
afc2f0a5be2fb3bd3355e04f45d827e9e73419bb,PMC,Monitoring for airborne respiratory viruses in a general pediatric ward in Singapore,http://dx.doi.org/10.4081/jphr.2019.1407,PMC6902309,31857987,CC BY-NC,"There is an increasing body of evidence suggesting that transmission of respiratory viruses occurs through the inhalation of virus-laden particles. Our study describes the use of an aerosol sampling system to monitor the prevalence of airborne viruses in a hospital setting. Using SKC AirCheck Touch pumps, with National Institute for Occupational Safety and Health (NIOSH) bioaerosol samplers and SKC filter cassette blanks, 28 aerosol samples were collected in a hospital ward in Singapore. Following DNA/RNA extraction, real-time RT-PCR/PCR was used for the detection of influenza A, B and D viruses, coronaviruses, enteroviruses, and adenoviruses. Airborne virus was detected in nine (32%) of 28 samples. Among the nine positive samples, eight were PCR-positive for adenovirus and one for influenza A virus. Our data suggest that bioaerosol sampling could be valuable in monitoring for airborne respiratory viruses in clinical environments to better understand the risk of infection during a hospital visit.",2019 Dec 4,"['Yadana, Su', 'Coleman, Kristen Kelli', 'Nguyen, Tham Thi', 'Hansen-Estruch, Christophe', 'Kalimuddin, Shirin', 'Thoon, Koh Cheng', 'Low, Jenny Guek Hong', 'Gray, Gregory Charles']",J Public Health Res,,,True
369acb7f90ebcfd6e59ab973c97ab233c5642b1a,PMC,Prevalence of feline immunodeficiency virus and feline leukaemia virus in domestic cats in Hungary,http://dx.doi.org/10.1177/2055116919892094,PMC6904780,31839979,CC BY-NC,"OBJECTIVES: Feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) are retroviruses affecting cats worldwide. The objectives of the study were to estimate the prevalence of these retroviruses in domestic cats in Hungary and to characterise the phylogenetic relationships of FIV strains. METHODS: A total of 335 anticoagulated whole-blood samples obtained from both a healthy and ill cat population were examined for the presence of FIV and FeLV with two methods: ELISA and PCR. Statistical analysis was carried out to analyse the data obtained. Sequencing and phylogenetic analysis of partial polymerase (pol) gene sequences was performed to describe circulating FIV subtypes. RESULTS: Statistical analysis showed 11.8% and 9.9% true prevalence of FeLV and FIV, respectively, with ELISA. The apparent prevalence calculated from the PCR results were 17.3% for FeLV and 13.1% for FIV. Phylogenetic analysis of partial pol gene sequences obtained from 22 FIV strains showed that all observed Hungarian strains belonged to FIV subtype B. The strains were grouped into several monophyletic subgroups reflecting the geographic locations of the origin of the samples. The overall mean genetic similarity between the analysed strains was 98.2%. CONCLUSIONS AND RELEVANCE: We report the first thorough overview of the prevalence of FeLV and FIV in Hungary, which is relatively high, and give insight into the genetic diversity of Hungarian strains of FIV.",2019 Dec 10,"['Szilasi, Anna', 'Dénes, Lilla', 'Krikó, Eszter', 'Heenemann, Kristin', 'Ertl, Reinhard', 'Mándoki, Míra', 'Vahlenkamp, Thomas W', 'Balka, Gyula']",JFMS Open Rep,,,True
22c00b12361acc7b59c2874d165c8f9bcee54b5d,PMC,Fill the gap between traditional and new era: The medical educational reform in Taiwan,http://dx.doi.org/10.4103/tcmj.tcmj_229_18,PMC6905246,31867248,CC BY-NC-SA,"The 7-year medical education program in Taiwan has been established since 1949. More than 60 years later, many medical professionals have observed and voiced its deficiencies following the outbreak of severe acute respiratory syndrome. The deficiencies are three-fold: (1) specialties are excessively institutionalized, (2) students engage in passive learning and memorization, and (3) passing one written national examination serves as the means of granting permanent physician qualification. The situation has aroused concerns and discussions among medical professionals and educators for a new medical education program. Authorized by the Conference of Deans of Medical Schools in Taiwan, Prof. Chyi-Her Lin assembled a team for planning medical curricular reform. Subsequently, Prof. Shan-Chwen Chang organized a task force team which has been monitoring the new 6-year program since 2013. The aims of medical reform by Prof. Lin are (1) to eliminate the specialty training part, (2) to use innovative teaching methods to motivate students to learn proactively, and (3) to implement competency-based medical education. Now, the first class of physicians will enter the workplace in 2019, subject to various clinical challenges.",2019 Sep 16,"['Cheng, Wei-Chun', 'Chen, Tsung-Ying', 'Lee, Ming-Shinn']",Ci Ji Yi Xue Za Zhi,,,True
940982caa84b1a49e2fd8b4dd0f12e2e904fc55b,PMC,Hemophagocytic lymphohistiocytosis in a patient with glioblastoma: a case report,http://dx.doi.org/10.2217/cns-2019-0013,PMC6912850,31777271,CC BY-NC-ND,"Adult onset hemophagocytic lymphohistiocytosis (HLH) is a rare condition, usually secondary to either a precipitating infective or hematologic malignancy. We present a case of Epstein–Barr virus associated HLH in a 55-year-old female receiving treatment for a glioblastoma (GBM). It is possible that HLH is under recognized, as patients with GBM often have features of a nonspecific systemic inflammatory response syndrome, multiorgan failure and cognitive decline. A high index of suspicion and increased awareness can help improve timeliness of diagnosis. Therapeutically, Epstein–Barr virus associated HLH in patients with solid organ malignancy poses significant challenges. An individualized, multidisciplinary approach is essential when managing adult-onset HLH and providers will need to be mindful of the high mortality rate despite treatment.",,"['Kumar, Vaibhav', 'Eulitt, Patrick J', 'Bermudez, Ana', 'Khagi, Simon']",CNS Oncol.; 8(4):CNS45,,,True
d89b71dc9725043b0a554e5b55791ef59e51d05a,PMC,Treating nasal symptoms associated with rhinitis using the intranasal herbal ointment Biyeom‐go: A prospective observational study,http://dx.doi.org/10.1111/coa.13425,PMC6916331,31468673,CC BY-NC-ND,"OBJECTIVES: The aim of the current study was to investigate the effectiveness and clinical feasibility of Biyeom‐go for the treatment of nasal symptoms associated with rhinitis. DESIGN: Prospective observational study. SETTING: This study was conducted at the Woosuk Korean Medicine Medical Center in South Korea. PARTICIPANTS: Fifty‐eight patients with rhinitis participated in this study. All patients received Biyeom‐go treatment >3 times daily for a total of 4 weeks. MAIN OUTCOME MEASURES: The primary outcome was the total nasal symptom score. Mini‐rhinoconjunctivitis quality of life questionnaire, nasal endoscopy index, total serum immunoglobulin E levels and immunologic factors in nasal lavage fluid were also measured. RESULTS: Biyeom‐go administration was associated with significant improvements in total nasal symptoms scores (P < .0001) and mini‐rhinoconjunctivitis quality of life questionnaire scores (P < .0001) in a time‐dependent manner. The nasal endoscopy index also significantly improved at weeks 2 (P = .0049), 3 (P < .0001) and 4 (P = .0001) after Biyeom‐go treatment. Significantly, increased interleukin‐2 levels (P = .005) and decreased interleukin‐8, chemokine (C‐C motif) ligand (CCL) 5, chemokine (C‐X‐C motif) ligand (CXCL) 9, CCL2 and CXCL10 levels were observed in the nasal lavage fluid. CONCLUSIONS: The present findings suggest that Biyeom‐go may be beneficial for the management of rhinitis symptoms and rhinitis‐associated quality of life. Further well‐designed randomised controlled trials are needed to evaluate the effectiveness of Biyeom‐go for rhinitis.",2019 Nov 29,"['Son, Mi Ju', 'Jung, Jeeyoun', 'Kim, Young‐Eun', 'Yeum, Chang‐Sub', 'Lee, So Min', 'Jung, So Young', 'Kwon, Ojin', 'Kim, Sungha', 'Kang, Jeong‐In', 'Kim, Hye‐Lin', 'Lee, Jung‐Eun', 'Lee, Dong‐Hyo']",Clin Otolaryngol,,,True
7d780290822a5408a54dfdf2ae32139cf1a2892c,PMC,"Epidemiology, Outcome and Risk Factors Analysis of Viral Infections in Children and Adolescents Undergoing Hematopoietic Cell Transplantation: Antiviral Drugs Do Not Prevent Epstein–Barr Virus Reactivation",http://dx.doi.org/10.2147/IDR.S224291,PMC6925545,31908501,CC BY-NC,"OBJECTIVE: The analysis of epidemiology, risk factors and outcome of viral infections in children and adolescents after hematopoietic cell transplantation (HCT). METHODS: In this multicenter nationwide study a total of 971 HCT procedures (741 allo-HCT; 230 auto-HCT) over a period of 6 years were analyzed. RESULTS: During this period 801 episodes of viral infections were diagnosed in 442 patients. The incidence of viral infections was 57.9% in allo-HCT and 4.8% in auto-HCT patients. The most frequent infections after allo-HCT were caused by cytomegalovirus (CMV), polyoma BK virus (BKV) and Epstein–Barr virus (EBV). The majority of infections occurred within the first 4 months after allo-HCT and over 80% required pharmacotherapy or symptomatic therapy. The median time of treatment of specific viral infection ranged from 7 (for EBV) to 24 (for CMV) days. The highest mortality was observed in case of CMV infection. The risk factors for viral infections were allo-HCT, acute leukemia, acute and chronic graft versus host disease (a/cGVHD), and matched unrelated donor (MUD)/mismatched unrelated donor (MMUD)-HCT. The risk factor for death from viral infection were CMV-IgG seropositivity in acute lymphoblastic leukemia recipient, and MUD/MMUD-HCT. The incidence of EBV infection requiring pre-emptive treatment with rituximab in allo-HCT children was 19.3%. In 30.8% cases of EBV infection, these episodes were preceded by other viral infection and treated with antivirals, which did not prevent development of EBV-DNA-emia with need of rituximab treatment in 81.5% cases. In 47.7% of these cases, GVHD was a factor enabling development of significant EBV-DNA-emia during antiviral therapy of other infection. CONCLUSION: We have shown that antiviral drugs do not prevent EBV reactivation in allo-HCT pediatric patients.",2019 Dec 17,"['Czyzewski, Krzysztof', 'Dziedzic, Magdalena', 'Salamonowicz, Malgorzata', 'Fraczkiewicz, Jowita', 'Zajac-Spychala, Olga', 'Zaucha-Prazmo, Agnieszka', 'Gozdzik, Jolanta', 'Galazka, Przemyslaw', 'Bartoszewicz, Natalia', 'Demidowicz, Ewa', 'Styczynski, Jan']",Infect Drug Resist,,,True
a94fd30a8dfce024118696e454bbe0f0e41840d9,PMC,The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose‐only exposure device,http://dx.doi.org/10.1002/ame2.12088,PMC6930991,31942559,CC BY-NC,"BACKGROUND: Middle East respiratory syndrome coronavirus (MERS‐CoV), which is not fully understood in regard to certain transmission routes and pathogenesis and lacks specific therapeutics and vaccines, poses a global threat to public health. METHODS: To simulate the clinical aerosol transmission route, hDPP4 transgenic mice were infected with MERS‐CoV by an animal nose‐only exposure device and compared with instillation‐inoculated mice. The challenged mice were observed for 14 consecutive days and necropsied on days 3, 5, 7, and 9 to analyze viral load, histopathology, viral antigen distribution, and cytokines in tissues. RESULTS: MERS‐CoV aerosol‐infected mice with an incubation period of 5‐7 days showed weight loss on days 7‐11, obvious lung lesions on day 7, high viral loads in the lungs on days 3‐9 and in the brain on days 7‐9, and 60% survival. MERS‐CoV instillation‐inoculated mice exhibited clinical signs on day 1, obvious lung lesions on days 3‐5, continuous weight loss, 0% survival by day 5, and high viral loads in the lungs and brain on days 3‐5. Viral antigen and high levels of proinflammatory cytokines and chemokines were detected in the aerosol and instillation groups. Disease, lung lesion, and viral replication progressions were slower in the MERS‐CoV aerosol‐infected mice than in the MERS‐CoV instillation‐inoculated mice. CONCLUSION: hDPP4 transgenic mice were successfully infected with MERS‐CoV aerosols via an animal nose‐only exposure device, and aerosol‐ and instillation‐infected mice simulated the clinical symptoms of moderate diffuse interstitial pneumonia. However, the transgenic mice exposed to aerosol MERS‐CoV developed disease and lung pathology progressions that more closely resembled those observed in humans.",2019 Oct 30,"['Hao, Xin‐yan', 'Lv, Qi', 'Li, Feng‐di', 'Xu, Yan‐feng', 'Gao, Hong']",Animal Model Exp Med,,,True
398bb77199ddb0d4e54efc14a1f1ef4c4ccb312b,PMC,Epidemics on networks: Reducing disease transmission using health emergency declarations and peer communication,http://dx.doi.org/10.1016/j.idm.2019.11.002,PMC6933230,31891014,CC BY-NC-ND,"Understanding individual decisions in a world where communications and information move instantly via cell phones and the internet, contributes to the development and implementation of policies aimed at stopping or ameliorating the spread of diseases. In this manuscript, the role of official social network perturbations generated by public health officials to slow down or stop a disease outbreak are studied over distinct classes of static social networks. The dynamics are stochastic in nature with individuals (nodes) being assigned fixed levels of education or wealth. Nodes may change their epidemiological status from susceptible, to infected and to recovered. Most importantly, it is assumed that when the prevalence reaches a pre-determined threshold level, [Formula: see text] , information, called awareness in our framework, starts to spread, a process triggered by public health authorities. Information is assumed to spread over the same static network and whether or not one becomes a temporary informer, is a function of his/her level of education or wealth and epidemiological status. Stochastic simulations show that threshold selection [Formula: see text] and the value of the average basic reproduction number impact the final epidemic size differentially. For the Erdős-Rényi and Small-world networks, an optimal choice for [Formula: see text] that minimize the final epidemic size can be identified under some conditions while for Scale-free networks this is not case.",2019 Dec 11,"['Azizi, Asma', 'Montalvo, Cesar', 'Espinoza, Baltazar', 'Kang, Yun', 'Castillo-Chavez, Carlos']",Infect Dis Model,,,False
4e5e41c6bee286394aab9998f7c4b2401a80333b,PMC,Pathogens Causing Respiratory Tract Infections in Children Less Than 5 Years of Age in Senegal,http://dx.doi.org/10.1177/1178636119890885,PMC6937528,31908474,CC BY-NC,"INTRODUCTION: While acute respiratory tract infections are the main cause of paediatric mortality and morbidity worldwide, pathogen patterns shift due to factors such as hygiene, vaccinations, and antibiotic resistance. Knowledge about current cause of respiratory infections is lacking, particularly in low- and middle-income countries. The aim of this study was to identity the various respiratory pathogens causing acute respiratory tract infections in children below 5 years of age visiting a sub-urban primary care clinic in Senegal. METHODS: A case-control study was performed in September and October 2018. Oropharyngeal swabs were collected from cases; infants with fever and respiratory symptoms, and controls; children involved in the vaccination programme. Viral identification was conducted by polymerase chain reaction for 21 different viruses; bacteria were identified by culture studies. Associations between microorganisms, acute respiratory infection and severity of disease were calculated by multivariate regression adjusting for confounders such as age, sex, and living area. RESULTS: Overall, 102 cases and 96 controls were included. Microorganisms were detected in 90.1% of cases and 53.7% of controls (P < .001). Influenza virus A (including H1N1), influenza virus B, respiratory syncytial virus (RSV), and Streptococcus pneumoniae were independently associated with acute respiratory tract infections. Co-detection of two or more pathogens was present in 49.5% of cases; 31.7% of cases had a pneumonia and 90.2% was treated with antibiotics. CONCLUSIONS: This case-control study in a primary care setting in sub-Saharan Africa found influenza virus A and B, RSV, and S pneumoniae to be the main causes of acute respiratory tract infections in children below 5 years of age. We recommend evaluation of antibiotics prescription behaviour in this setting.",2019 Dec 30,"['Knobbe, Rebecca B', 'Diallo, Abdallah', 'Fall, Amary', 'Gueye, Aida D', 'Dieng, Assane', 'van Immerzeel, Tabitha D', 'Ba, Abou', 'Diop, Amadou', 'Diop, Abdoulaye', 'Niang, Mbayame', 'Boye, Cheikh SB']",Microbiol Insights,,,True
a4490fc5ca8fea133b9a5beb9258df89cf4945b6,PMC,PRSS contributes to cetuximab resistance in colorectal cancer,http://dx.doi.org/10.1126/sciadv.aax5576,PMC6938705,31911942,CC BY-NC,"Cetuximab improves the survival of patients with metastatic colorectal cancer. The main limitation is primary and secondary resistance, the underlying mechanism of which requires extensive investigation. We proved that PRSS expression levels are significantly negatively associated with the sensitivity of cancer cells to cetuximab. Detailed mechanistic analysis indicated that PRSS can cleave cetuximab, leading to resistance. Cetuximab or bevacizumab combined with SPINK1, a PRSS inhibitor, inhibited cell growth more efficiently than cetuximab or bevacizumab alone in xenograft models. PRSS levels in the serum of 156 patients with mCRC were analyzed, and poor efficacy of cetuximab therapy was observed in patients with aberrant PRSS expression. PRSS expression in monoclonal antibody (mAb)–treated patients with cancer from The Cancer Genome Atlas database was also evaluated to determine whether patients with higher PRSS expression have significantly reduced progression-free survival. Our work provides a strong scientific rationale for targeting PRSS in combination with cetuximab therapy.",2020 Jan 1,"['Tan, Zhaoli', 'Gao, Lihua', 'Wang, Yan', 'Yin, Huihui', 'Xi, Yongyi', 'Wu, Xiaojie', 'Shao, Yong', 'Qiu, Weiyi', 'Du, Peng', 'Shen, Wenlong', 'Fu, Ling', 'Jia, Ru', 'Zhao, Chuanhua', 'Zhang, Yun', 'Zhao, Zhihu', 'Sun, Zhiwei', 'Chen, Hongxing', 'Hu, Xianwen', 'Xu, Jianming', 'Wang, Youliang']",Sci Adv,,,True
72dd846d7517f98a1e13b79fe4e7f9f6482356e3,PMC,PRSS contributes to cetuximab resistance in colorectal cancer,http://dx.doi.org/10.1126/sciadv.aax5576,PMC6938705,31911942,CC BY-NC,"Cetuximab improves the survival of patients with metastatic colorectal cancer. The main limitation is primary and secondary resistance, the underlying mechanism of which requires extensive investigation. We proved that PRSS expression levels are significantly negatively associated with the sensitivity of cancer cells to cetuximab. Detailed mechanistic analysis indicated that PRSS can cleave cetuximab, leading to resistance. Cetuximab or bevacizumab combined with SPINK1, a PRSS inhibitor, inhibited cell growth more efficiently than cetuximab or bevacizumab alone in xenograft models. PRSS levels in the serum of 156 patients with mCRC were analyzed, and poor efficacy of cetuximab therapy was observed in patients with aberrant PRSS expression. PRSS expression in monoclonal antibody (mAb)–treated patients with cancer from The Cancer Genome Atlas database was also evaluated to determine whether patients with higher PRSS expression have significantly reduced progression-free survival. Our work provides a strong scientific rationale for targeting PRSS in combination with cetuximab therapy.",2020 Jan 1,"['Tan, Zhaoli', 'Gao, Lihua', 'Wang, Yan', 'Yin, Huihui', 'Xi, Yongyi', 'Wu, Xiaojie', 'Shao, Yong', 'Qiu, Weiyi', 'Du, Peng', 'Shen, Wenlong', 'Fu, Ling', 'Jia, Ru', 'Zhao, Chuanhua', 'Zhang, Yun', 'Zhao, Zhihu', 'Sun, Zhiwei', 'Chen, Hongxing', 'Hu, Xianwen', 'Xu, Jianming', 'Wang, Youliang']",Sci Adv,,,False
17f00e096a5f3ce94278a77011e6f38d7a47c618,PMC,Tumor‐associated macrophages secrete CC‐chemokine ligand 2 and induce tamoxifen resistance by activating PI3K/Akt/mTOR in breast cancer,http://dx.doi.org/10.1111/cas.14230,PMC6942430,31710162,CC BY-NC,"Breast cancer is the most prevalent malignancy among women. Although endocrine therapy is effective, the development of endocrine resistance is a major clinical challenge. The tumor microenvironment (TME) promotes tumor malignancy, and tumor‐associated macrophages (TAM) within the TME play a crucial role in endocrine resistance. Herein, we aimed to elucidate the relationship between TAM and the endocrine‐resistant phenotype of breast cancer. Macrophages were cultured with conditioned medium (CM) from tamoxifen‐sensitive (MCF7‐S) or ‐resistant (MCF7‐R) MCF7 breast cancer cells. M2 polarization was detected by CD163 immunofluorescence. To determine the effect on endocrine resistance, MCF7 cells were cultured in the supernatant of different TAM, and then treated with tamoxifen. CC‐chemokine ligand 2 (CCL2) immunohistochemistry was carried out on pathological sections from 100 patients with invasive estrogen receptor‐positive breast cancer. We found that macrophages cultured in the CM of MCF7‐S and MCF7‐R cells were induced into TAM, with a more obvious M2 polarization in the latter. Tamoxifen resistance was increased by culture in TAM medium. TAM secreted CCL2, which increased endocrine resistance in breast cancer cells through activation of the PI3K/Akt/mTOR signaling pathway. High expression of CCL2 was correlated with infiltration of CD163+macrophages (r = 0.548, P < .001), and patients with high CCL2 expression presented shorter progression‐free survival than those with low CCL2 expression (P < .05). We conclude that CCL2 secreted by TAM activates PI3K/Akt/mTOR signaling and promotes an endocrine resistance feedback loop in the TME, suggesting that CCL2 and TAM may be novel therapeutic targets for patients with endocrine‐resistant breast cancer.",2020 Jan 19,"['Li, Dongbo', 'Ji, Hongfei', 'Niu, Xingjian', 'Yin, Lei', 'Wang, Yiran', 'Gu, Yucui', 'Wang, Jinlu', 'Zhou, Xiaoping', 'Zhang, Han', 'Zhang, Qingyuan']",Cancer Sci,,,True
eac8ac161c5889bb47d90400f3bc2fb1ab32f3ff,PMC,Clinical findings and treatment of disseminated ‘Mycobacterium avium subspecies hominissuis’ infection in a domestic cat,http://dx.doi.org/10.1292/jvms.19-0492,PMC6943314,31666444,CC BY-NC-ND,"A cat was referred because of diffuse parenchymal lung disease. Close examinations revealed a swollen abdominal lymph node and multiple nodules of the liver. Mycobacterium avium subspecies hominissuis infection was confirmed by culture and single nucleotide polymorphism analysis of samples recovered from the liver and bronchoalveolar lavage. After administration of combination antibiotics for 6 months, culture results were negative. Though atonic seizures were observed during the treatment, it disappeared after isoniazid discontinuation and pyridoxal phosphate administration. On day 771 of illness, no clinical signs, lung diseases, or obvious swelling of lymph nodes was observed. This is the first report to confirm Mycobacterium avium subspecies hominissuis infection in cats through gene analysis and to completely cure it with combination antibiotics.",2019 Dec 31,"['KANEGI, Ryoji', 'YASUGI, Mayo', 'NABETANI, Tomoyo', 'TANAKA, Toshiyuki', 'WADA, Yusuke', 'HIRAI, Kotaro', 'SUGIURA, Kikuya', 'HATOYA, Shingo']",J Vet Med Sci,,,True
8cfedfcfe692d38a55444702e704325ad1163277,PMC,Phenobarbital-induced anticonvulsant hypersensitivity syndrome in a cat,http://dx.doi.org/10.1292/jvms.19-0388,PMC6943318,31685729,CC BY-NC-ND,"In this study, we document a case of phenobarbital-induced anticonvulsant hypersensitivity syndrome (AHS), which has been rarely reported in veterinary medicine. A 2-year-old, 5.4 kg, neutered male Russian Blue cat was diagnosed with idiopathic epilepsy and started on phenobarbital treatment. Eight days after initiation of phenobarbital treatment, the cat showed tachypnea and hyperthermia. CBC and serum biochemistry were unremarkable. However, the patient showed high serum amyloid A (SAA). On abdominal ultrasonography, generalized enlargement of abdominal lymph nodes and splenic multiple hypo-echoic nodules, which were consistent with reactive lymphadenopathy were found. The cat was diagnosed with AHS, and phenobarbital was discontinued. After 10 days of cessation, the patient had normal SAA, and clinical signs were resolved.",2019 Dec 4,"['SOHN, Sang-June', 'JEUNG, So-Young', 'CHAE, Hyung-Kyu', 'CHO, Hee-Seon', 'AN, Ju-Hyun', 'LI, Qiang', 'SONG, Woo-Jin', 'YOUN, Hwa-Young']",J Vet Med Sci,,,True
99be48475fc986f16d752a56ceeed588e4f74818,PMC,Evaluation of serological assays available in a biosafety level 2 laboratory and their application for survey of Middle East respiratory syndrome coronavirus among livestock in Ethiopia,http://dx.doi.org/10.1292/jvms.19-0436,PMC6943330,31685722,CC BY-NC-ND,"A serological survey of Middle East respiratory syndrome coronavirus (MERS-CoV) was conducted among dromedary camels and herbivorous animals sharing the same pasturage in Ethiopia. The pseudotyped vesicular stomatitis virus coated with the spike protein of MERS-CoV was used in virus neutralization (VN) tests performed in a biosafety level (BSL)-2 laboratory. The results were similar to those obtained from the VN test using live MERS-CoV and were more sensitive than the ELISA performed using synthetic MERS S1 fragment as the antigen as well as the competitive ELISA performed using a monoclonal antibody against MERS-CoV. According to the comprehensive results of the four types of serodiagnosis methods, positive antibodies were detected only in dromedary camels and the remaining herbivorous animals were not infected with the virus. Moreover, using the present procedure, serological tests for MERS-CoV can be conducted even in BSL 2 laboratory.",2019 Dec 5,"['TERAMICHI, Takurou', 'FUKUSHI, Shuetsu', 'HACHIYA, Yuma', 'MELAKU, Simenew Keskes', 'OGUMA, Keisuke', 'SENTSUI, Hiroshi']",J Vet Med Sci,,,True
b6ea35cdd357c55dddb3b9732487e664a26cc502,PMC,Evaluation of antiviral - passive - active immunization (“sandwich”) therapeutic strategy for functional cure of chronic hepatitis B in mice,http://dx.doi.org/10.1016/j.ebiom.2019.10.043,PMC6945269,31680000,CC BY-NC-ND,"BACKGROUND: Chronic Hepatitis B (CHB) remains a major problem for global public health. Viral persistence and immune defects are the two major reasons for CHB, and it was hypothesized that based on a transient clearance of serum viral DNA and HBsAg “window stage”, active immunization against hepatitis B virus (HBV) might initiate effective host immune responses versus HBV to achieve functional cure of CHB. METHODS: Two experimental mouse models that mice hydrodynamic injected HBV DNA or infected with recombinant AAV/HBV were used. The “sandwich” therapeutic effect by using a potent human anti-HBsAg neutralizing monoclonal antibody (G12) in combination with antiviral drug tenofovir disoproxil fumarate (TDF), followed by active immunization with HBsAg-HBsAb (mYIC) was evaluated. FINDINGS: A single G12 injection rapidly cleared serum HBsAg in HDI-HBV carrier mice, with a synergistic effect in decreasing viral DNA load when TDF was given orally. When both serum viral DNA and HBsAg load became low or undetectable, mYIC was administered. A more effective clearance of viral DNA and HBsAg was observed and serum HBsAb was developed only in these “sandwich”-treated mice. Efficient intrahepatic anti-HBV immune responses were also observed in these mice, including the formation of aggregates of myeloid cells with CD8(+)T cells and increased TNF-α, granzyme B production. INTERPRETATION: The “sandwich” combination therapy not only efficiently decreased HBsAg and HBV DNA levels but also induced effective cellular and humoral immunity, which may result in functional cure of CHB.",2019 Nov 1,"['Shi, Bisheng', 'Wu, Yanling', 'Wang, Chunyu', 'Li, Xiaofang', 'Yu, Fan', 'Wang, Bin', 'Yang, Zhenlin', 'Li, Jianhua', 'Liang, Mifang', 'Wen, Yumei', 'Ying, Tianlei', 'Yuan, Zhenghong']",EBioMedicine,,,False
4178b81e61b88d5cc07ca0253875007e93e9a7f5,PMC,Nanomedicine for Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome,http://dx.doi.org/10.1159/000477086,PMC6945951,31988911,CC BY-NC,"Acute lung injury and acute respiratory distress syndrome (ARDS) represent a heterogenous group of lung disease in critically ill patients that continues to have high mortality. Despite the increased understanding of the molecular pathogenesis of ARDS, specific targeted treatments for ARDS have yet to be developed. ARDS represents an unmet medical need with an urgency to develop effective pharmacotherapies. Multiple promising targets have been identified that could lead to the development of potential therapies for ARDS; however, they have been limited because of difficulty with the mode of delivery, especially in critically ill patients. Nanobiotechnology is the basis of innovative techniques to deliver drugs targeted to the site of inflamed organs, such as the lungs. Nanoscale drug delivery systems have the ability to improve the pharmacokinetics and pharmacodynamics of agents, allowing an increase in the biodistribution of therapeutic agents to target organs and resulting in improved efficacy with reduction in drug toxicity. Although attractive, delivering nanomedicine to lungs can be challenging as it requires sophisticated systems. Here we review the potential of novel nanomedicine approaches that may prove to be therapeutically beneficial for the treatment of this devastating condition.",2017 Jun 27,"['Sadikot, Ruxana T.', 'Kolanjiyil, Arun V.', 'Kleinstreuer, Clement', 'Rubinstein, Israel']",Biomed Hub,,,True
ca247deecd89fea456e741ed2a23a8e1213471c3,PMC,Focusing on Families and Visitors Reduces Healthcare Associated Respiratory Viral Infections in a Neonatal Intensive Care Unit,http://dx.doi.org/10.1097/pq9.0000000000000242,PMC6946222,32010868,CC BY-NC-ND,"Healthcare-associated respiratory viral infections (HARVIs) result in significant harm to infants in the neonatal intensive care unit (NICU). Healthcare workers and visitors can serve as transmission vectors to patients. We hypothesized that improved family and visitor hand hygiene (FVHH) and visitor screening would reduce HARVIs by at least 25%. METHODS: This quality improvement project took place in a large tertiary NICU to reduce HARVIs. Interventions primarily focused on improving FVHH and reducing visitation by symptomatic family members and visitors. We defined correct FVHH as hand hygiene performed immediately before touching their child. Hand hygiene observations were performed by direct observation by NICU staff using a standardized tool. Interventions to improve FVHH included education of staff and visitors, reminder signs, and immediate reminders to families to prevent lapses in hand hygiene. Staff screened family and visitors before NICU entry. Symptomatic individuals were asked to defer visitation until symptoms resolved. HARVIs were identified during prospective surveillance by infection preventionists using standard definitions. RESULTS: Baseline FVHH was 27% in 2015. After May 2017, the average FVHH remained at 85%. When reminded, family members and visitors performed hand hygiene 99% of the time. Staff screened ~129,000 people for FVHH. Between January 2013 and March 2019, there were 74 HARVIs; 80% were rhinovirus/enterovirus. After the implementation of improved FVHH, the HARVI rate decreased from 0.67 to 0.23/1,000 patient days. CONCLUSIONS: Adding interventions to improve FVHH and visitor management to existing healthcare worker prevention efforts can help reduce HARVIs in the NICU.",2019 Dec 16,"['Linam, W. Matthew', 'Marrero, Elizabeth M.', 'Honeycutt, Michele D.', 'Wisdom, Christy M.', 'Gaspar, Anna', 'Vijayan, Vini']",Pediatr Qual Saf,,,True
80443ac4a7af83c776c6c895683e66907f66e28e,PMC,Focusing on Families and Visitors Reduces Healthcare Associated Respiratory Viral Infections in a Neonatal Intensive Care Unit,http://dx.doi.org/10.1097/pq9.0000000000000242,PMC6946222,32010868,CC BY-NC-ND,"Healthcare-associated respiratory viral infections (HARVIs) result in significant harm to infants in the neonatal intensive care unit (NICU). Healthcare workers and visitors can serve as transmission vectors to patients. We hypothesized that improved family and visitor hand hygiene (FVHH) and visitor screening would reduce HARVIs by at least 25%. METHODS: This quality improvement project took place in a large tertiary NICU to reduce HARVIs. Interventions primarily focused on improving FVHH and reducing visitation by symptomatic family members and visitors. We defined correct FVHH as hand hygiene performed immediately before touching their child. Hand hygiene observations were performed by direct observation by NICU staff using a standardized tool. Interventions to improve FVHH included education of staff and visitors, reminder signs, and immediate reminders to families to prevent lapses in hand hygiene. Staff screened family and visitors before NICU entry. Symptomatic individuals were asked to defer visitation until symptoms resolved. HARVIs were identified during prospective surveillance by infection preventionists using standard definitions. RESULTS: Baseline FVHH was 27% in 2015. After May 2017, the average FVHH remained at 85%. When reminded, family members and visitors performed hand hygiene 99% of the time. Staff screened ~129,000 people for FVHH. Between January 2013 and March 2019, there were 74 HARVIs; 80% were rhinovirus/enterovirus. After the implementation of improved FVHH, the HARVI rate decreased from 0.67 to 0.23/1,000 patient days. CONCLUSIONS: Adding interventions to improve FVHH and visitor management to existing healthcare worker prevention efforts can help reduce HARVIs in the NICU.",2019 Dec 16,"['Linam, W. Matthew', 'Marrero, Elizabeth M.', 'Honeycutt, Michele D.', 'Wisdom, Christy M.', 'Gaspar, Anna', 'Vijayan, Vini']",Pediatr Qual Saf,,,False
19a8fa406706ba3ec843407622cbcf241f992029,PMC,Focusing on Families and Visitors Reduces Healthcare Associated Respiratory Viral Infections in a Neonatal Intensive Care Unit,http://dx.doi.org/10.1097/pq9.0000000000000242,PMC6946222,32010868,CC BY-NC-ND,"Healthcare-associated respiratory viral infections (HARVIs) result in significant harm to infants in the neonatal intensive care unit (NICU). Healthcare workers and visitors can serve as transmission vectors to patients. We hypothesized that improved family and visitor hand hygiene (FVHH) and visitor screening would reduce HARVIs by at least 25%. METHODS: This quality improvement project took place in a large tertiary NICU to reduce HARVIs. Interventions primarily focused on improving FVHH and reducing visitation by symptomatic family members and visitors. We defined correct FVHH as hand hygiene performed immediately before touching their child. Hand hygiene observations were performed by direct observation by NICU staff using a standardized tool. Interventions to improve FVHH included education of staff and visitors, reminder signs, and immediate reminders to families to prevent lapses in hand hygiene. Staff screened family and visitors before NICU entry. Symptomatic individuals were asked to defer visitation until symptoms resolved. HARVIs were identified during prospective surveillance by infection preventionists using standard definitions. RESULTS: Baseline FVHH was 27% in 2015. After May 2017, the average FVHH remained at 85%. When reminded, family members and visitors performed hand hygiene 99% of the time. Staff screened ~129,000 people for FVHH. Between January 2013 and March 2019, there were 74 HARVIs; 80% were rhinovirus/enterovirus. After the implementation of improved FVHH, the HARVI rate decreased from 0.67 to 0.23/1,000 patient days. CONCLUSIONS: Adding interventions to improve FVHH and visitor management to existing healthcare worker prevention efforts can help reduce HARVIs in the NICU.",2019 Dec 16,"['Linam, W. Matthew', 'Marrero, Elizabeth M.', 'Honeycutt, Michele D.', 'Wisdom, Christy M.', 'Gaspar, Anna', 'Vijayan, Vini']",Pediatr Qual Saf,,,False
5d58ccdb0252429f7c74ece67b505a2afd7e08c9,PMC,Viral Pneumonia Requiring Differentiation from Acute and Progressive Diffuse Interstitial Lung Diseases,http://dx.doi.org/10.2169/internalmedicine.2696-19,PMC6949447,31839671,CC BY-NC-ND,"OBJECTIVE: The clinical characteristics and chest imaging findings of viral pneumonia and several interstitial lung diseases (ILDs) overlap, and viral pneumonia may be underrecognized and misdiagnosed as certain ILDs. To clarify the frequency of viral pneumonia among patients with acute progressive clinical courses that required a differential diagnosis between ILDs and pneumonia, and to determine the most frequent ILDs misdiagnosed in cases of viral pneumonia. PATIENTS AND METHODS: We retrospectively analyzed patients hospitalized from 2010 to 2017 with an acute clinical course (≤30 days) who underwent bronchoalveolar lavage (BAL) for the differential diagnosis of infection and ILDs. We performed a multiplex PCR for respiratory viruses using the patients' preserved BAL fluid. The final diagnosis was made by a multidisciplinary approach and after considering the PCR results. The diagnosis at discharge was compared to the final diagnosis. RESULTS: Among the 109 patients, 53 were diagnosed with viral pneumonia. Viral pneumonia and other diseases showed some differences in symptoms and laboratory data; however, the differences were small or overlapped. Viral pneumonia was misdiagnosed on discharge as acute fibrinous organizing pneumonia, cryptogenic organizing pneumonia, or chronic eosinophilic pneumonia (AFOP/COP/CEP) (n=22), acute interstitial pneumonia (n=5), connective tissue disease-related ILDs (n=3), unclassifiable interstitial pneumonia (n=2), drug-induced ILD (n=1), and pneumonia (n=20). CONCLUSION: Approximately half of the patients who underwent BAL had viral pneumonia. The most common ILD-related misdiagnoses were AFOP/COP/CEP. Differences in symptoms and laboratory findings between viral pneumonia and other diseases were small, and viral pneumonia should be included in the differential diagnosis when physicians encounter cases in which the abovementioned ILDs are suspected.",2019 Dec 15,"['Ishiguro, Takashi', 'Kobayashi, Yasuhito', 'Uozumi, Ryuji', 'Takata, Naomi', 'Takaku, Yotaro', 'Kagiyama, Naho', 'Kanauchi, Tetsu', 'Shimizu, Yoshihiko', 'Takayanagi, Noboru']",Intern Med,,,True
54560eb4cc2e0affe21b8b21435c907232764c8a,PMC,Current Status of Porcine Epidemic Diarrhoea (PED) in European Pigs,http://dx.doi.org/10.2478/jvetres-2019-0064,PMC6950429,31934654,CC BY-NC-ND,"Porcine epidemic diarrhoea (PED) is a highly contagious and devastating enteric disease of pigs caused by porcine epidemic diarrhoea virus (PEDV), an enveloped, single-stranded RNA virus belonging to the Alphacoronavirus genus of the Coronaviridae family. The disease is clinically similar to other forms of porcine gastroenteritis. Pigs are the only known host of the disease, and the occurrence of PED in wild boars is unknown. The virus causes acute diarrhoea, vomiting, dehydration, and high mortality in suckling piglets reaching 100%. Heavy economic losses in the pig-farming industry were sustained in the USA between 2013 and 2015 when PEDV spread very quickly and resulted in epidemics. The loss in the US pig industry has been estimated at almost seven million pigs. The purpose of this review is a description of the current status of porcine epidemic diarrhoea in European pigs and the risk presented by the introduction of PEDV to Poland in comparison to the epidemics in the USA.",2019 Oct 24,"['Antas, Marta', 'Woźniakowski, Grzegorz']",J Vet Res,,,True
064fc5c0af69e9be13dee69a113ca743d05fd807,PMC,Highly sensitive simultaneous electrochemical determination of myricetin and rutin via solid phase extraction on a ternary Pt@r-GO@MWCNTs nanocomposite,http://dx.doi.org/10.1016/j.jpha.2019.03.009,PMC6951492,31929945,CC BY-NC-ND,"The simultaneous electrochemical determination of myricetin and rutin remains a challenge due to their indistinguishable potentials. To solve this problem, we constructed a ternary platinum nanoparticle, reduced graphene oxide, multi-walled carbon nanotubes (Pt@r-GO@MWCNTs) nanocomposite via a facile one-pot synthetic method. Under the optimized conditions, the ternary Pt@r-GO@MWCNTs nanocomposite exhibited good electrocatalytic activity toward myricetin and rutin via solid phase extraction and excellent performance for the simultaneous determination of myricetin and rutin. The oxidation peak current of myricetin was proportional to its concentrations in the range of 0.05–50 μM with a detection limit of 0.01 μM (S/N = 3). The linear range for rutin was 0.05–50 μM with a detection limit of 0.005 μM (S/N = 3). The ternary nanocomposite sensor also exhibited good reproducibility and stability, and was successfully used for the simultaneous determination of myricetin and rutin in real orange juice samples with recoveries ranging between 100.57% and 108.46%.",2019 Oct 22,"['Tursynbolat, Satar', 'Bakytkarim, Yrysgul', 'Huang, Jianzhi', 'Wang, Lishi']",J Pharm Anal,,,False
0f506a74e190c45a399f382c153919612fa1ef5b,PMC,Integrated Cross-Species Analysis Identifies a Conserved Transitional Dendritic Cell Population,http://dx.doi.org/10.1016/j.celrep.2019.11.042,PMC6951814,31825848,CC BY-NC-ND,"Plasmacytoid dendritic cells (pDCs) are sensor cells with diverse immune functions, from type I interferon (IFN-I) production to antigen presentation, T cell activation, and tolerance. Regulation of these functions remains poorly understood but could be mediated by functionally specialized pDC subpopulations. We address pDC diversity using a high-dimensional single-cell approach: mass cytometry (CyTOF). Our analysis uncovers a murine pDC-like population that specializes in antigen presentation with limited capacity for IFN-I production. Using a multifaceted cross-species comparison, we show that this pDC-like population is the definitive murine equivalent of the recently described human AXL(+) DCs, which we unify under the name transitional DCs (tDCs) given their continuum of pDC and cDC2 characteristics. tDCs share developmental traits with pDCs, as well as recruitment dynamics during viral infection. Altogether, we provide a framework for deciphering the function of pDCs and tDCs during diseases, which has the potential to open new avenues for therapeutic design.",2019 Dec 10,"['Leylek, Rebecca', 'Alcántara-Hernández, Marcela', 'Lanzar, Zachary', 'Lüdtke, Anja', 'Perez, Oriana A.', 'Reizis, Boris', 'Idoyaga, Juliana']",Cell Rep,,,True
caaa1e0e60a860b078465c328e73a2c201b53554,PMC,Integrated Cross-Species Analysis Identifies a Conserved Transitional Dendritic Cell Population,http://dx.doi.org/10.1016/j.celrep.2019.11.042,PMC6951814,31825848,CC BY-NC-ND,"Plasmacytoid dendritic cells (pDCs) are sensor cells with diverse immune functions, from type I interferon (IFN-I) production to antigen presentation, T cell activation, and tolerance. Regulation of these functions remains poorly understood but could be mediated by functionally specialized pDC subpopulations. We address pDC diversity using a high-dimensional single-cell approach: mass cytometry (CyTOF). Our analysis uncovers a murine pDC-like population that specializes in antigen presentation with limited capacity for IFN-I production. Using a multifaceted cross-species comparison, we show that this pDC-like population is the definitive murine equivalent of the recently described human AXL(+) DCs, which we unify under the name transitional DCs (tDCs) given their continuum of pDC and cDC2 characteristics. tDCs share developmental traits with pDCs, as well as recruitment dynamics during viral infection. Altogether, we provide a framework for deciphering the function of pDCs and tDCs during diseases, which has the potential to open new avenues for therapeutic design.",2019 Dec 10,"['Leylek, Rebecca', 'Alcántara-Hernández, Marcela', 'Lanzar, Zachary', 'Lüdtke, Anja', 'Perez, Oriana A.', 'Reizis, Boris', 'Idoyaga, Juliana']",Cell Rep,,,True
869a5a7ca9cf0fc9a2f5cd0332ac7c6b8e8e2ab9,PMC,Integrated Cross-Species Analysis Identifies a Conserved Transitional Dendritic Cell Population,http://dx.doi.org/10.1016/j.celrep.2019.11.042,PMC6951814,31825848,CC BY-NC-ND,"Plasmacytoid dendritic cells (pDCs) are sensor cells with diverse immune functions, from type I interferon (IFN-I) production to antigen presentation, T cell activation, and tolerance. Regulation of these functions remains poorly understood but could be mediated by functionally specialized pDC subpopulations. We address pDC diversity using a high-dimensional single-cell approach: mass cytometry (CyTOF). Our analysis uncovers a murine pDC-like population that specializes in antigen presentation with limited capacity for IFN-I production. Using a multifaceted cross-species comparison, we show that this pDC-like population is the definitive murine equivalent of the recently described human AXL(+) DCs, which we unify under the name transitional DCs (tDCs) given their continuum of pDC and cDC2 characteristics. tDCs share developmental traits with pDCs, as well as recruitment dynamics during viral infection. Altogether, we provide a framework for deciphering the function of pDCs and tDCs during diseases, which has the potential to open new avenues for therapeutic design.",2019 Dec 10,"['Leylek, Rebecca', 'Alcántara-Hernández, Marcela', 'Lanzar, Zachary', 'Lüdtke, Anja', 'Perez, Oriana A.', 'Reizis, Boris', 'Idoyaga, Juliana']",Cell Rep,,,True
b22c9aa91ec989861466462585e303956e6ae949,PMC,Metformin Inhibits Proliferation of Human Thyroid Cancer TPC-1 Cells by Decreasing LRP2 to Suppress the JNK Pathway,http://dx.doi.org/10.2147/OTT.S227915,PMC6954091,32021253,CC BY-NC,"OBJECTIVE: To uncover the potential effect of metformin on proliferation and apoptosis of thyroid cancer TPC-1 cell line, and the underlying mechanism. METHODS: Viability, apoptosis and LRP2 level in TPC-1 cells treated with different doses of metformin for different time points were determined. Besides, protein levels of p-JNK1 and c-Jun N-terminal kinases (JNK) in metformin-treated TPC-1 cells were detected by Western blot. Regulatory effects of LRP2 on the JNK pathway and cell viability in metformin-treated TPC-1 cells were assessed. RESULTS: Viability in TPC-1 cells gradually decreased with the treatment of increased doses of metformin either for 24 h or 48 h. The apoptotic rate was concentration-dependently elevated by metformin treatment. Relative levels of LRP2 and p-JNK1 were concentration-dependently downregulated by metformin treatment. In addition, overexpression of LRP2 partially abolished the inhibitory effect of metformin on the viability of TPC-1 cells. CONCLUSION: Metformin treatment suppresses the proliferative ability and induces apoptosis of TPC-1 cells by downregulating LRP2 to block the JNK pathway.",2020 Jan 6,"['He, Yang', 'Cao, Lingling', 'Wang, Li', 'Liu, Lingping', 'Huang, Ying', 'Gong, Xuan']",Onco Targets Ther,,,True
e3bc735859aa567bbb943a3c48e8e0da30b3c99e,PMC,Implementation System of a Biosurveillance System in the Republic of Korea and Its Legal Ramifications,http://dx.doi.org/10.1089/hs.2019.0071,PMC6964808,31800333,CC BY-NC,"Laws are fundamental tools that regulate and manage various issues to protect the rights of the people in a society. Legislation on disease surveillance enables agencies to regulate and manage public health, including preventing the spread of infectious diseases. We assessed the Infectious Disease Prevention and Control Act of Korea (IDPCA) through the lens of biosurveillance to understand its effectiveness in protecting public health. In addition, the relevant legislation and regulations of the United States and the World Health Organization were examined. The evaluation concludes that the current IDPCA is limited in terms of providing guidance for early detection of and response to hazards using integrated data and an information-sharing system. Further revision of the laws is needed to enable early detection and warning of potential threats to public health.",2019 Dec 1,"['Kim, Amanda J.', 'Tak, Sangwoo']",Health Secur,,,True
920ac358de68e48b50b4d65dc500935ade21c997,PMC,Virus-induced immunosuppression in turkeys (Meleagris gallopavo): A review,http://dx.doi.org/10.4314/ovj.v9i4.13,PMC6971353,32042658,CC BY-NC,"Immunosuppression is characterized by a dysfunction of humoral and/or cellular immune response leading to increase of susceptibility to secondary infections, increase of mortality and morbidity, poor productivity, and welfare and vaccination failures. Humoral immune response depression is due to perturbation of soluble factors, as complement and chemokines in innate immunity and antibodies or cytokines in adaptive immunity. At the cellular immune response, immunosuppression is the consequence of the dysfunction of T-cells, B-cells, heterophils, monocytes, macrophages, and natural Killer cells. Immunosuppression in turkeys can be caused by numerous, non-infectious, and infectious agents, having variable pathological and molecular mechanisms. Interactions between them are very complex. This paper reviews the common viruses inducing clinical and sub-clinical immunosuppression in turkeys, and enteric and neoplastic viruses in particular, as well as the interactions among them. The evaluation of immunosuppression is currently based on classical approach; however, new technique such as the microarray technology is being developed to investigate immunological mediator’s genes detection. Controlling of immunosuppression include, in general, biosecurity practices, maintaining appropriate breeding conditions and vaccination of breeders and their progeny. Nevertheless, few vaccines are available against immunosuppressive viruses in turkey’s industry. The development of new control strategies is reviewed.",2020 Jan 25,"Kaboudi, Khaled",Open Vet J,,,True
c5ad260f605645f5fe9da46ff2c2738984ef9ff8,PMC,Proceedings 31st Symposium ESVN‐ECVN,http://dx.doi.org/10.1111/jvim.15647,PMC6979112,31863606,CC BY-NC,,2020 Dec 21 Jan-Feb,,J Vet Intern Med,,,False
cfe337afa069a02e96adf6894819e7928f8c4534,PMC,Long‐term outcome of cats with acquired myasthenia gravis without evidence of a cranial mediastinal mass,http://dx.doi.org/10.1111/jvim.15655,PMC6979264,31746510,CC BY-NC-ND,"BACKGROUND: Acquired myasthenia gravis (AMG) is increasingly recognized in cats, yet information regarding the natural history of the disease, treatment, and outcome including occurrence of immune and spontaneous remission remains limited. OBJECTIVE: To determine the long‐term outcome of cats with AMG without evidence of a cranial mediastinal mass (CMM). ANIMALS: Eight cats diagnosed with AMG without evidence of a CMM. METHODS: Retrospective case series. The medical records of cats diagnosed with AMG between 2005 and 2018 from 2 veterinary referral hospitals were reviewed for inclusion. Inclusion criteria consisted of a diagnosis of AMG, thoracic imaging, serum biochemistry including measurement of creatine kinase, and a CBC. Exclusion criteria were the presence of an identifiable CMM, or administration of methimazole or carbimazole. RESULTS: All cats had an excellent long‐term outcome, achieving immune remission within 6 months of diagnosis, including 4 cats that did not receive any treatment and whose natural course of disease involved spontaneous remission. Clinical presentation was heterogeneous, and skeletal muscle weakness and fatigability induced or exacerbated by the wheelbarrow exercise stress test were the most consistent abnormalities associated with AMG. CONCLUSION AND CLINICAL IMPORTANCE: Cats diagnosed with AMG without evidence a CMM have a favorable outcome and frequently achieve immune remission. Moreover, the natural history of AMG in cats includes spontaneous remission when there is no evidence of a CMM. Attempting to rule out the presence of a CMM therefore refines prognosis, and treatment is not always necessary in this disease population.",2020 Nov 20 Jan-Feb,"['Mignan, Thomas', 'Garosi, Laurent', 'Targett, Mike', 'Lowrie, Mark']",J Vet Intern Med,,,True
0036b28fddf7e93da0970303672934ea2f9944e7,PMC,Research Communications of the 29th ECVIM‐CA Congress,http://dx.doi.org/10.1111/jvim.15658,PMC6979267,31837159,CC BY-NC,,2020 Dec 14 Jan-Feb,,J Vet Intern Med,,,True
71b8c50ee0e1f4e79e6618301b768befbf943a5d,PMC,Inflammatory and microbiological associations with near-fatal asthma requiring extracorporeal membrane oxygenation,http://dx.doi.org/10.1183/23120541.00267-2019,PMC6983494,32010717,CC BY-NC,Patients with near-fatal asthma requiring ECMO are more likely to be younger and female and are also likely to have positive viral and fungal isolates on bronchoalveolar lavage when compared to those receiving conventional mechanical ventilation http://bit.ly/2S38SaC,2020 Jan 27,"['Patel, Sunil', 'Shah, Neeraj M.', 'Malhotra, Akanksha M.', 'Lockie, Christopher', 'Camporota, Luigi', 'Barrett, Nicholas', 'Kent, Brian D.', 'Jackson, David J.']",ERJ Open Res,,,True
e18773ecee762195cee18f1b3d83ef02f2db0dc9,PMC,Recomendaciones para el manejo de la faringoamigdalitis aguda del adulto(),http://dx.doi.org/10.1016/j.aprim.2015.02.002,PMC6983836,26025360,CC BY-NC-ND,"Acute pharyngitis in adults is one of the most common infectious diseases seen in general practitioners’ consultations. Viral aetiology is the most common. Among bacterial causes, the main agent is Streptococcus pyogenes or group A β-haemolytic streptococcus (GABHS), which causes 5%-30% of the episodes. In the diagnostic process, clinical assessment scales can help clinicians to better predict suspected bacterial aetiology by selecting patients who should undergo a rapid antigen detection test. If these techniques are not performed, an overdiagnosis of streptococcal pharyngitis often occurs, resulting in unnecessary prescriptions of antibiotics, most of which are broad spectrum. Consequently, management algorithms that include the use of predictive clinical rules and rapid tests have been set up. The aim of the treatment is speeding up symptom resolution, reducing the contagious time span and preventing local suppurative and non-suppurative complications. Penicillin and amoxicillin are the antibiotics of choice for the treatment of pharyngitis. The association of amoxicillin and clavulanate is not indicated as the initial treatment of acute infection. Neither are macrolides indicated as first-line therapy; they should be reserved for patients allergic to penicillin. The appropriate diagnosis of bacterial pharyngitis and proper use of antibiotics based on the scientific evidence available are crucial. Using management algorithms can be helpful in identifying and screening the cases that do not require antibiotic therapy.",2015 Oct 27,"['Cots, Josep M.', 'Alós, Juan-Ignacio', 'Bárcena, Mario', 'Boleda, Xavier', 'Cañada, José L.', 'Gómez, Niceto', 'Mendoza, Ana', 'Vilaseca, Isabel', 'Llor, Carles']",Aten Primaria,,,False
db4a4b2bde1bf1bb981bf87f9c6c25462834a25e,PMC,Intracellular Vesicle Fusion Requires a Membrane-Destabilizing Peptide Located at the Juxtamembrane Region of the v-SNARE,http://dx.doi.org/10.1016/j.celrep.2019.11.107,PMC6990648,31875562,CC BY-NC-ND,"Intracellular vesicle fusion is mediated by soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs) and Sec1/Munc18 (SM) proteins. It is generally accepted that membrane fusion occurs when the vesicle and target membranes are brought into close proximity by SNAREs and SM proteins. In this work, we demonstrate that, for fusion to occur, membrane bilayers must be destabilized by a conserved membrane-embedded motif located at the juxtamembrane region of the vesicle-anchored v-SNARE. Comprised of basic and hydrophobic residues, the juxtamembrane motif perturbs the lipid bilayer structure and promotes SNARE-SM-mediated membrane fusion. The juxtamembrane motif can be functionally substituted with an unrelated membrane-disrupting peptide in the membrane fusion reaction. These findings establish the juxtamembrane motif of the v-SNARE as a membrane-destabilizing peptide. Requirement of membrane-destabilizing peptides is likely a common feature of biological membrane fusion.",2019 Dec 24,"['Rathore, Shailendra S.', 'Liu, Yinghui', 'Yu, Haijia', 'Wan, Chun', 'Lee, MyeongSeon', 'Yin, Qian', 'Stowell, Michael H.B.', 'Shen, Jingshi']",Cell Rep,,,True
ba34dcc49e18899e68cf4bed58d3fafb94845496,PMC,Intracellular Vesicle Fusion Requires a Membrane-Destabilizing Peptide Located at the Juxtamembrane Region of the v-SNARE,http://dx.doi.org/10.1016/j.celrep.2019.11.107,PMC6990648,31875562,CC BY-NC-ND,"Intracellular vesicle fusion is mediated by soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs) and Sec1/Munc18 (SM) proteins. It is generally accepted that membrane fusion occurs when the vesicle and target membranes are brought into close proximity by SNAREs and SM proteins. In this work, we demonstrate that, for fusion to occur, membrane bilayers must be destabilized by a conserved membrane-embedded motif located at the juxtamembrane region of the vesicle-anchored v-SNARE. Comprised of basic and hydrophobic residues, the juxtamembrane motif perturbs the lipid bilayer structure and promotes SNARE-SM-mediated membrane fusion. The juxtamembrane motif can be functionally substituted with an unrelated membrane-disrupting peptide in the membrane fusion reaction. These findings establish the juxtamembrane motif of the v-SNARE as a membrane-destabilizing peptide. Requirement of membrane-destabilizing peptides is likely a common feature of biological membrane fusion.",2019 Dec 24,"['Rathore, Shailendra S.', 'Liu, Yinghui', 'Yu, Haijia', 'Wan, Chun', 'Lee, MyeongSeon', 'Yin, Qian', 'Stowell, Michael H.B.', 'Shen, Jingshi']",Cell Rep,,,False
1bed4f8a5412cfa315b0936705a647059ceaec62,PMC,The Fight against the 2019-nCoV Outbreak: an Arduous March Has Just Begun,http://dx.doi.org/10.3346/jkms.2020.35.e56,PMC6995816,31997618,CC BY-NC,,2020 Jan 30,"Yoo, Jin-Hong",J Korean Med Sci,,,True
11888535f2eb67c15d08783b164def90aa47a3bd,PMC,Pre-Treatment with Zirconia Nanoparticles Reduces Inflammation Induced by the Pathogenic H5N1 Influenza Virus,http://dx.doi.org/10.2147/IJN.S221667,PMC6996547,32099358,CC BY-NC,"BACKGROUND: New approaches are urgently needed to fight influenza viral infection. Previous research has shown that zirconia nanoparticles can be used as anticancer materials, but their antiviral activity has not been reported. Here, we investigated the antiviral effect of zirconia (ZrO(2)) nanoparticles (NPs) against a highly pathogenic avian influenza virus. MATERIALS AND METHODS: In this study, the antiviral effects of ZrO(2) on H5N1 virus were assessed in vivo, and the molecular mechanism responsible for this protection was investigated. RESULTS: Mice treated with 200 nm positively-charged NPs at a dose of 100 mg/kg showed higher survival rates and smaller reductions in weight. 200 nm ZrO(2) activated mature dendritic cells and initially promoted the expression of cytokines associated with the antiviral response and innate immunity. In the lungs of H5N1-infected mice, ZrO(2) treatment led to less pathological lung injury, significant reduction in influenza A virus replication, and overexpression of pro-inflammatory cytokines. CONCLUSION: This antiviral study using zirconia NPs shows protection of mice against highly pathogenic avian influenza virus and suggests strong application potential for this method, introducing a new tool against a wide range of microbial infections.",2020 Jan 30,"['Huo, Caiyun', 'Xiao, Jin', 'Xiao, Kai', 'Zou, Shumei', 'Wang, Ming', 'Qi, Peng', 'Liu, Tianlong', 'Hu, Yanxin']",Int J Nanomedicine,,,True
c23db0f0dc55dea350cd7e27939acad930c6c85a,PMC,Identifying factors and target preventive therapies for Middle East Respiratory Syndrome sucsibtable patients,http://dx.doi.org/10.1016/j.jsps.2019.11.016,PMC7000305,32042254,CC BY-NC-ND,"BACKGROUND: Middle East Respiratory Syndrome (MERS) is a respiratory disease caused by a novel coronavirus that was identified in 2012 in Saudi Arabia. It is associated with significant mortality and morbidity. We identified factors associated with the Middle East Respiratory Syndrome-Coronavirus (MERS‐CoV) infection among suspected cases presented with sign and symptoms of upper respiratory infection or exposure to the virus. We also looked at the impact of medication history on virus transmission. METHOD: We included subjects with suspected MERS-CoV infection and confirmed cases of MERS infection. Subjects were excluded if there were any missing data that prevent the final analysis. Descriptive statistics were used to report demographic data. Percentages and frequencies were used to summarize the categorical variables, while means and standard deviations were calculated for continuous variables. Logistic regression was used to assess the risk of MERS-CoV infection among the suspected cases. A value of p < 0.05 was considered statistically significant. RESULTS: A total of 16,189 suspected cases were identified, complete data were analyzed for 3154 to assess factors that are independently associated with MERS-CoV infection. MERS-CoV infection was associated with age (adjusted odds ratio [AOR] = 1.06; 95% CI [1.02–1.098], P-value = 0.004), male gender (AOR = 1.617; 95% CI [1.365–1.77], P-value < 0.001) and diabetes (AOR = 1.68; 95% CI [1.346–1.848], P-value = 0.002. There was no significant association with the other comorbidities. Medication history was not associated with an increase or decrease the likelihood of the infection. CONCLUSIONS: MERS-Cov infection is more common in male, advanced age and diabetes. No medications were associated with an increase or decrease the likelihood of the infection. This is important to focus on screening and detection to this patient population.",2020 Feb 7,"['Alburikan, Khalid A.', 'Abuelizz, Hatem A.']",Saudi Pharm J,,,False
acbe63db4d9bb13ebde8af3b75b797cb29bbd5cb,PMC,Assessment of hemagglutination activity of porcine deltacoronavirus,http://dx.doi.org/10.4142/jvs.2020.21.e12,PMC7000906,31940691,CC BY-NC,"Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus that causes diarrhea in piglets. However, the biological characteristics of PDCoV are unclear. In this study, the hemagglutination (HA) abilities of two PDCoV strains (CH-01 and HNZK-04) were investigated. Our results showed that PDCoV has the ability to agglutinate rabbit erythrocytes after virion pretreatment with trypsin or neuraminidase. Additionally, the HA assay results showed a significant positive correlation with the infectious viral titer. Our results suggest that assessing the HA activity of PDCoV may be a useful diagnostic method for investigating and surveilling PDCoV infections.",2020 Jan 13,"['Zhang, Yunfei', 'Han, Li', 'Xia, Lu', 'Yuan, Yixin', 'Hu, Hui']",J Vet Sci,,,True
9e924e077420d14dc2f532673769a45c2f424527,PMC,Approaches for patients with very high MELD scores,http://dx.doi.org/10.1016/j.jhepr.2019.02.008,PMC7001538,32039352,CC BY-NC-ND,"In the era of the “sickest first” policy, patients with very high model for end-stage liver disease (MELD) scores have been increasingly admitted to the intensive care unit with the expectation that they will receive a liver transplant (LT) in the absence of improvement on supportive therapies. Such patients are often admitted in a context of acute-on-chronic liver failure with extrahepatic failures. Sequential assessment of scores or classification based on organ failures within the first days after admission help to stratify the risk of mortality in this population. Although the prognosis of severely ill cirrhotic patients has recently improved, transplant-free mortality remains high. LT is still the only curative treatment in this population. Yet, the increased relative scarcity of graft resource must be considered alongside the increased risk of losing a graft in the initial postoperative period when performing LT in “too sick to transplant” patients. Variables associated with poor immediate post-LT outcomes have been identified in large studies. Despite this, the performance of scores based on these variables is still insufficient. Consideration of a patient’s comorbidities and frailty is an appealing predictive approach in this population that has proven of great value in many other diseases. So far, local expertise remains the last safeguard to LT. Using this expertise, data are accumulating on favourable post-LT outcomes in very high MELD populations, particularly when LT is performed in a situation of stabilization/improvement of organ failures in selected candidates. The absence of “definitive” contraindications and the control of “dynamic” contraindications allow a “transplantation window” to be defined. This window must be identified swiftly after admission given the poor short-term survival of patients with very high MELD scores. In the absence of any prospect of LT, withdrawal of care could be discussed to ensure respect of patient life, dignity and wishes.",2019 Feb 23,"['Artru, Florent', 'Samuel, Didier']",JHEP Rep,,,False
2d4246494e250c90bb5721a35e2b0a8e20100f20,PMC,"Comparative genomics of hepatitis A virus, hepatitis C virus, and hepatitis E virus provides insights into the evolutionary history of Hepatovirus species",http://dx.doi.org/10.1002/mbo3.973,PMC7002107,31742930,CC BY-NC-ND,"The intraspecies genomic diversity of the single‐strand RNA (+) virus species hepatitis A virus (Hepatovirus), hepatitis C virus (Hepacivirus), and hepatitis E virus (Orthohepevirus) was compared. These viral species all can cause liver inflammation (hepatitis), but share no gene similarity. The codon usage of human hepatitis A virus (HAV) is suboptimal for replication in its host, a characteristic it shares with taxonomically related rodent, simian, and bat hepatitis A virus species. We found this codon usage to be strikingly similar to that of Triatoma virus that infects blood‐sucking kissing bugs. The codon usage of that virus is well adapted to its insect host. The codon usage of HAV is also similar to other invertebrate viruses of various taxonomic families. An evolutionary ancestor of HAV and related virus species is hypothesized to be an insect virus that underwent a host jump to infect mammals. The similarity between HAV and invertebrate viruses goes beyond codon usage, as they also share amino acid composition characteristics, while not sharing direct sequence homology. In contrast, hepatitis C virus and hepatitis E virus are highly similar in codon usage preference, nucleotide composition, and amino acid composition, and share these characteristics with Human pegivirus A, West Nile virus, and Zika virus. We present evidence that these observations are only partly explained by differences in nucleotide composition of the complete viral codon regions. We consider the combination of nucleotide composition, amino acid composition, and codon usage preference suitable to provide information on possible evolutionary similarities between distant virus species that cannot be investigated by phylogeny.",2019 Nov 19,"['Wassenaar, Trudy M.', 'Jun, Se‐Ran', 'Robeson, Michael', 'Ussery, David W.']",Microbiologyopen,,,True
9c4444ada7a386ec68c8180c998e0b2ec44824d8,PMC,Icariin promotes osteogenic differentiation of BMSCs by upregulating BMAL1 expression via BMP signaling,http://dx.doi.org/10.3892/mmr.2020.10954,PMC7002972,32016461,CC BY-NC-ND,"Increasing research has demonstrated that expression of brain and muscle ARNT-like 1 (BMAL1) and other circadian clock genes can be regulated by drugs and toxicants. We previously demonstrated that icariin, extracted from Herba Epimedii, sromotes osteogenic differentiation. However, the mechanism underlying the association between icariin and BMAL1 in osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) remains unclear. The present study was designed with an aim to clarify the association between icariin and BMAL1 in osteogenic differentiation of BMSCs. The Cell Counting Kit-8 assay was used to evaluate cell proliferation. The expression of bone morphogenetic protein 2 (BMP2), RUNX family transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OC) and BMAL1 in BMSCs was evaluated by reverse transcription-quantitative PCR and western blotting. ALP and Alizarin red S (ARS) staining were also performed. Icariin promoted BMSC proliferation, and upregulated expression of osteogenic genes and BMAL1. In addition, expression of the osteogenic genes BMP2, RUNX2, ALP and OC were upregulated by BMAL1 overexpression. Furthermore, we confirmed that BMAL1 deficiency suppressed osteogenic differentiation in BMSCs. Finally, ARS staining of BMAL1(−/−) BMSCs revealed that BMAL1 was an essential intermediary in matrix mineralization during osteogenic differentiation. In conclusion, these results demonstrated that icariin promoted osteogenic differentiation through BMAL1-BMP2 signaling in BMSCs. The present study thus described a novel target of icariin that has potential applications in the treatment of osteogenic disorders.",2020 Mar 20,"['Huang, Zengfa', 'Wei, Hui', 'Wang, Xiang', 'Xiao, Jianwei', 'Li, Zuoqin', 'Xie, Yuanliang', 'Hu, Yun', 'Li, Xiang', 'Wang, Zheng', 'Zhang, Shutong']",Mol Med Rep,,,True
01af2562df4acf3113843d039c3b82bb801b1427,PMC,Chest Computed Tomography Abnormalities and Their Relationship to the Clinical Manifestation of Respiratory Syncytial Virus Infection in a Genetically Confirmed Outbreak,http://dx.doi.org/10.2169/internalmedicine.3117-19,PMC7008051,31941871,CC BY-NC-ND,"Studies reporting chest images of respiratory syncytial virus (RSV)-induced lower respiratory tract infection (LRTI) in an outbreak setting and their relationship to the clinical manifestation are limited. During a genetically confirmed RSV outbreak, eight patients underwent both chest X-ray and computed tomography (CT). Among these, 5 cases had newly appearing abnormalities on CT, although chest X-ray was able to detect abnormalities in only 2 cases (40%). Although bronchial wall thickening was common, other findings and their distribution were variable, even in an outbreak setting. All patients with both a history of anticancer chemotherapy against hematological cancer and lower respiratory symptoms, such as wheezing, sputum, and hypoxemia, had abnormalities on CT, suggesting that these two factors might be important for predicting the existence of LRTI in RSV-infected patients.",2020 Jan 15,"['Nabeya, Daijiro', 'Kinjo, Takeshi', 'Parrott, Gretchen Lynn', 'Nakachi, Sawako', 'Yamashiro, Tomoko', 'Ikemiyagi, Nanae', 'Arakaki, Wakako', 'Masuzaki, Hiroaki', 'Fujita, Jiro']",Intern Med,,,True
8318896fad2acf22ac94d15d6d571dd2f7cf121d,PMC,The Outbreak Cases with the Novel Coronavirus Suggest Upgraded Quarantine and Isolation in Korea,http://dx.doi.org/10.3346/jkms.2020.35.e62,PMC7008072,32030926,CC BY-NC,,2020 Feb 3,"['Yoo, Jin-Hong', 'Hong, Sung-Tae']",J Korean Med Sci,,,True
dc7ae96ed471da2388e3d63cc70fe1ee30a297ae,PMC,"The First Case of 2019 Novel Coronavirus Pneumonia Imported into Korea from Wuhan, China: Implication for Infection Prevention and Control Measures",http://dx.doi.org/10.3346/jkms.2020.35.e61,PMC7008073,32030925,CC BY-NC,"In December 2019, a viral pneumonia outbreak caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV), began in Wuhan, China. We report the epidemiological and clinical features of the first patient with 2019-nCoV pneumonia imported into Korea from Wuhan. This report suggests that in the early phase of 2019-nCoV pneumonia, chest radiography would miss patients with pneumonia and highlights taking travel history is of paramount importance for early detection and isolation of 2019-nCoV cases.",2020 Feb 3,"['Kim, Jin Yong', 'Choe, Pyoeng Gyun', 'Oh, Yoonju', 'Oh, Kyung Joong', 'Kim, Jinsil', 'Park, So Jeong', 'Park, Ji Hye', 'Na, Hye Kyoung', 'Oh, Myoung-don']",J Korean Med Sci,,,True
a6f40ea4a3c00f065ee24e7be886e3cc48a3a6bd,PMC,The rOX‐stars of inflammation: links between the inflammasome and mitochondrial meltdown,http://dx.doi.org/10.1002/cti2.1109,PMC7008497,32055400,CC BY-NC-ND,"The nod‐like receptor protein 3 (NLRP3) inflammasome drives inflammation in response to mitochondrial dysfunction. As metabolic powerhouses with prokaryotic ancestry, mitochondria are a cache for danger‐associated molecular patterns and pathogen‐associated molecular pattern‐like molecules that elicit potent innate immune responses. Persistent mitochondrial damage caused by infection, or genetic or environmental factors, can lead to inappropriate or sustained inflammasome signalling. Here, we review the features of mitochondria that drive inflammatory signalling, with a particular focus on mitochondrial activation of the NLRP3 inflammasome. Given that mitochondrial network dynamics, metabolic activity and redox state are all intricately linked to each other and to NLRP3 inflammasome activity, we highlight the importance of a holistic approach to investigations of NLRP3 activation by dysfunctional mitochondria.",2020 Feb 10,"['Holley, Caroline L', 'Schroder, Kate']",Clin Transl Immunology,,,True
cfa3dd16b97bf8c51a0106577a0a639bcc706142,PMC,Syndromic Surveillance System for MERS-CoV as New Early Warning and Identification Approach,http://dx.doi.org/10.2147/RMHP.S239984,PMC7008581,32104115,CC BY-NC,This commentary presents a novel outlook for public health authorities in the affected countries to detect and respond quickly to the emerging public health threats such as Middle East respiratory syndrome coronavirus (MERS-CoV). Implementing an innovative electronic surveillance system called syndromic surveillance system is essential for global health security.,2020 Feb 5,"['Salamatbakhsh, Maryam', 'Mobaraki, Kazhal', 'Ahmadzadeh, Jamal']",Risk Manag Healthc Policy,,,True
b43fc42df698fbc829757a0dac65d9bce3d8f054,PMC,A novel loop-mediated isothermal amplification method for efficient and robust detection of EGFR mutations,http://dx.doi.org/10.3892/ijo.2020.4961,PMC7010225,32124949,CC BY-NC-ND,"The activation of somatic mutations conferring sensitivity to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors has been widely used in the development of advanced or metastatic primary lung cancer therapy. Therefore, identification of EGFR mutations is essential. In the present study, a loop-mediated isothermal amplification (LAMP) method was used to identify EGFR mutations, and its efficiency was compared with the Therascreen quantitative PCR assay. Using LAMP and Therascreen to analyze surgically resected tissue samples from patients with pulmonary adenocarcinoma, EGFR mutations were observed in 32/59 tumor samples (LAMP) and 33/59 tumor samples (Therascreen). Notably, the LAMP assay identified one tumor as wild-type, which had previously been identified as a deletion mutation in exon 19 via the Therascreen assay (Case X). However, the direct sequencing to confirm the EGFR status of the Case X adhered to the results of the LAMP assay. Further experiments using Case X DNA identified this exon 19 deletion mutation using both methods. In addition, a novel deletion mutation in exon 19 of the EGFR was identified. Overall, the present study shows that the LAMP method may serve as a valuable alternative for the identification oncogene mutations.",2020 Jan 14,"['Horiuchi, Sho', 'Saito, Yuichi', 'Matsui, Atsuka', 'Takahashi, Nobumasa', 'Ikeya, Tomohiko', 'Hoshi, Eishin', 'Shimizu, Yoshihiko', 'Yasuda, Masanori']",Int J Oncol,,,True
aa33c034390b9db8e458730ebc92b1da7668aedf,PMC,A novel loop-mediated isothermal amplification method for efficient and robust detection of EGFR mutations,http://dx.doi.org/10.3892/ijo.2020.4961,PMC7010225,32124949,CC BY-NC-ND,"The activation of somatic mutations conferring sensitivity to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors has been widely used in the development of advanced or metastatic primary lung cancer therapy. Therefore, identification of EGFR mutations is essential. In the present study, a loop-mediated isothermal amplification (LAMP) method was used to identify EGFR mutations, and its efficiency was compared with the Therascreen quantitative PCR assay. Using LAMP and Therascreen to analyze surgically resected tissue samples from patients with pulmonary adenocarcinoma, EGFR mutations were observed in 32/59 tumor samples (LAMP) and 33/59 tumor samples (Therascreen). Notably, the LAMP assay identified one tumor as wild-type, which had previously been identified as a deletion mutation in exon 19 via the Therascreen assay (Case X). However, the direct sequencing to confirm the EGFR status of the Case X adhered to the results of the LAMP assay. Further experiments using Case X DNA identified this exon 19 deletion mutation using both methods. In addition, a novel deletion mutation in exon 19 of the EGFR was identified. Overall, the present study shows that the LAMP method may serve as a valuable alternative for the identification oncogene mutations.",2020 Jan 14,"['Horiuchi, Sho', 'Saito, Yuichi', 'Matsui, Atsuka', 'Takahashi, Nobumasa', 'Ikeya, Tomohiko', 'Hoshi, Eishin', 'Shimizu, Yoshihiko', 'Yasuda, Masanori']",Int J Oncol,,,False
d51dd0a976e0d01e1be8d21d301c7ed8843fc89e,PMC,"Hospital-based surveillance of influenza A(H1N1)pdm09 virus in Saudi Arabia, 2010-2016",http://dx.doi.org/10.5144/0256-4947.2020.1,PMC7012031,32026719,CC BY-NC-ND,"BACKGROUND: Influenza is a highly contagious acute viral respiratory tract infection. The emergence of influenza A(H1N1)pdm09 in 2009 caused a pandemic. Since then it has become a seasonal influenza virus. It causes symptoms ranging from mild to severe illness, which might be fatal, particularly in people with underlying chronic medical conditions, immunocompromised people, the elderly, and pregnant women. OBJECTIVE: Describe the data generated by the influenza A(H1N1) pdm09 surveillance in Saudi Arabia from 2010 to 2016. DESIGN: Retrospective, descriptive. SETTING: Hospitals reporting to the Ministry of Health. MATERIALS AND METHODS: We studied aggregate data on hospitalized cases of influenza A(H1N1)pdm09 in Saudi Arabia between 2010 and 2016. The surveillance system used the case definition proposed by the WHO. The cases were confirmed by performing the real-time PCR (polymerase chain reaction) on upper respiratory samples. MAIN OUTCOME MEASURES: Suspected and confirmed influenza A(H1N1)pdm09 cases. SAMPLE SIZE: 113 502 suspected H1N1 cases and 17 094 (15.1%) confirmed cases. RESULTS: Most of the reported cases were registered in the Riyadh region. During the period of the study, the highest number of confirmed cases, 9262 (54.2 %), was in 2015. The case fatality rate for confirmed cases was 3.6%. CONCLUSION: Influenza A(H1N1)pdm09 showed seasonal trends. The number of suspected influenza cases each year was proportionate to the number of confirmed cases for that year. Riyadh, Jeddah and the Eastern areas (regions with the highest population) reported most of the cases. LIMITATION: Only one strain of H1N1 was tested. CONFLICT OF INTEREST: None.",2020 Jan 6 Jan-Feb,"['Abdalla, Osman', 'Mohammed, Mutaz', 'Hakawi, Ahmed Mohammed', 'Aljifri, Alanoud', 'Abdalla, Mohamed', 'Eltigani, Sara', 'Mujib, Sahibzada Azhar', 'Assiri, Abdullah']",Ann Saudi Med,,,True
3e039d09e97b28724f19438f21fcebab6c15c986,PMC,The 10th Anniversary of Asia Pacific Allergy,http://dx.doi.org/10.5415/apallergy.2020.10.e10,PMC7016318,32099832,CC BY-NC,,2020 Jan 31,"Chang, Yoon-Seok",Asia Pac Allergy,,,True
4b36607cdbc54f8006161a9a1839489dd0a51269,PMC,A qualitative study of zoonotic risk factors among rural communities in southern China,http://dx.doi.org/10.1093/inthealth/ihaa001,PMC7017878,32040190,CC BY-NC,"BACKGROUND: Strategies are urgently needed to mitigate the risk of zoonotic disease emergence in southern China, where pathogens with zoonotic potential are known to circulate in wild animal populations. However, the risk factors leading to emergence are poorly understood, which presents a challenge in developing appropriate mitigation strategies for local communities. METHODS: Residents in rural communities of Yunnan, Guangxi and Guangdong provinces were recruited and enrolled in this study. Data were collected through ethnographic interviews and field observations, and thematically coded and analysed to identify both risk and protective factors for zoonotic disease emergence at the individual, community and policy levels. RESULTS: Eighty-eight ethnographic interviews and 55 field observations were conducted at nine selected sites. Frequent human–animal interactions and low levels of environmental biosecurity in local communities were identified as risks for zoonotic disease emergence. Policies and programmes existing in the communities provide opportunities for zoonotic risk mitigation. CONCLUSIONS: This study explored the relationship among zoonotic risk and human behaviour, environment and policies in rural communities in southern China. It identifies key behavioural risk factors that can be targeted for development of tailored risk-mitigation strategies to reduce the threat of novel zoonoses.",2020 Feb 10,"['Li, Hong-Ying', 'Zhu, Guang-Jian', 'Zhang, Yun-Zhi', 'Zhang, Li-Biao', 'Hagan, Emily A', 'Martinez, Stephanie', 'Chmura, Aleksei A', 'Francisco, Leilani', 'Tai, Hina', 'Miller, Maureen', 'Daszak, Peter']",Int Health,,,True
aaa7097797afbe1f79128eccfcb4050b98cabd72,PMC,A qualitative study of zoonotic risk factors among rural communities in southern China,http://dx.doi.org/10.1093/inthealth/ihaa001,PMC7017878,32040190,CC BY-NC,"BACKGROUND: Strategies are urgently needed to mitigate the risk of zoonotic disease emergence in southern China, where pathogens with zoonotic potential are known to circulate in wild animal populations. However, the risk factors leading to emergence are poorly understood, which presents a challenge in developing appropriate mitigation strategies for local communities. METHODS: Residents in rural communities of Yunnan, Guangxi and Guangdong provinces were recruited and enrolled in this study. Data were collected through ethnographic interviews and field observations, and thematically coded and analysed to identify both risk and protective factors for zoonotic disease emergence at the individual, community and policy levels. RESULTS: Eighty-eight ethnographic interviews and 55 field observations were conducted at nine selected sites. Frequent human–animal interactions and low levels of environmental biosecurity in local communities were identified as risks for zoonotic disease emergence. Policies and programmes existing in the communities provide opportunities for zoonotic risk mitigation. CONCLUSIONS: This study explored the relationship among zoonotic risk and human behaviour, environment and policies in rural communities in southern China. It identifies key behavioural risk factors that can be targeted for development of tailored risk-mitigation strategies to reduce the threat of novel zoonoses.",2020 Feb 10,"['Li, Hong-Ying', 'Zhu, Guang-Jian', 'Zhang, Yun-Zhi', 'Zhang, Li-Biao', 'Hagan, Emily A', 'Martinez, Stephanie', 'Chmura, Aleksei A', 'Francisco, Leilani', 'Tai, Hina', 'Miller, Maureen', 'Daszak, Peter']",Int Health,,,False
c439e1028bc93d94f4eba1855c6b1eade676f732,PMC,Acute Respiratory Distress Syndrome as an Organ Phenotype of Vascular Microthrombotic Disease: Based on Hemostatic Theory and Endothelial Molecular Pathogenesis,http://dx.doi.org/10.1177/1076029619887437,PMC7019416,31775524,CC BY-NC,"Acute respiratory distress syndrome (ARDS) is a life-threatening noncardiogenic circulatory disorder of the lungs associated with critical illnesses such as sepsis, trauma, and immune and collagen vascular disease. Its mortality rate is marginally improved with the best supportive care. The demise occurs due to progressive pulmonary hypoxia and multi-organ dysfunction syndrome (MODS) with severe inflammation. Complement activation is a part of immune response against pathogen or insult in which membrane attack complex (MAC) is formed and eliminates microbes. If complement regulatory protein such as endothelial CD59 is underexpressed, MAC may also cause pulmonary vascular injury to the innocent bystander endothelial cell of host and provokes endotheliopathy that causes inflammation and pulmonary vascular microthrombosis, leading to ARDS. Its pathogenesis is based on a novel “two-path unifying theory” of hemostasis and “two-activation theory of the endothelium” promoting molecular pathogenesis. Endotheliopathy activates two independent molecular pathways: inflammatory and microthrombotic. The former triggers the release inflammatory cytokines and the latter promotes exocytosis of unusually large von Willebrand factor multimers (ULVWF) and platelet activation. Inflammatory pathway initiates inflammation, but microthrombotic pathway more seriously produces “microthrombi strings” composed of platelet-ULVWF complexes, which become anchored on the injured endothelial cells, and causes disseminated intravascular microthrombosis (DIT). DIT is a hemostatic disease due to lone activation of ULVWF path without activated tissue factor path. It leads to endotheliopathy-associated vascular microthrombotic disease (EA-VMTD), which orchestrates consumptive thrombocytopenia, microangiopathic hemolytic anemia, and MODS. Thrombotic thrombocytopenic purpura (TTP)-like syndrome is the hematologic phenotype of EA-VMTD. ARDS is one of organ phenotypes among MODS associated with TTP-like syndrome. The most effective treatment of ARDS can be achieved by counteracting the activated microthrombotic pathway based on two novel hemostatic theories.",2019 Nov 28,"Chang, Jae C.",Clin Appl Thromb Hemost,,,True
f0e75f3b4aeda66ce88ca4a58a785c8fdf32b9ab,PMC,Suspension culture of Vero cells for the production of adenovirus type 5,http://dx.doi.org/10.7774/cevr.2020.9.1.48,PMC7024729,32095440,CC BY-NC,"PURPOSE: Most cell culture processes for viral vaccine production are mainly based on adherent cell culture systems using serum, which are associated with expensive and labor-intensive processes to produce large amounts of viral vaccine strains. In this study, we investigated whether Vero cells could be grown in serum-free and shaking suspension conditions. Furthermore, we assessed the ability of the Vero cell suspension culture system to produce adenovirus type 5 (Ad5), compared to that of the adhesive Vero cell culture system. MATERIALS AND METHODS: We tested the feasibility of commercial serum-free media for Vero cell culture. For the adaptation of Vero cells in suspension culture, adhesive Vero cells were added in the early phase of shaking suspension culture, and 50 days after shaking suspension culture, suspension-adapted Vero cells were subcultured continuously. To assess the virus production ability of Vero cells in suspension, the cells were infected with Ad5-green fluorescent protein and evaluated based on their fluorescence intensity. RESULTS: The Vero cells grown in OptiPRO serum-free medium showed no changes in morphology and growth rate, but MRC-5 and FRhk-4 cells showed morphological changes and decreased growth rate, respectively. The Vero cells were well adapted to the suspension culture system. The Vero cells in suspension showed a better Ad5 production ability than the adherent Vero cells. CONCLUSION: Vero cells can be grown in OptiPRO serum-free medium. Further, our suspension culture-adapted Vero cells may be suitable to produce viral vaccine strains due to their high ability to produce viruses such as Ad5.",2020 Jan 31,"['Lee, Deuk-Ki', 'Park, Jihye', 'Seo, Dong-Won']",Clin Exp Vaccine Res,,,True
f0a7684b84d874e9d61eee9c4cff37bb45bb2547,PMC,Case of the Index Patient Who Caused Tertiary Transmission of Coronavirus Disease 2019 in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Pneumonia Monitored by Quantitative RT-PCR,http://dx.doi.org/10.3346/jkms.2020.35.e79,PMC7025910,32056407,CC BY-NC,"Since mid-December of 2019, coronavirus disease 2019 (COVID-19) has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.",2020 Feb 14,"['Lim, Jaegyun', 'Jeon, Seunghyun', 'Shin, Hyun-Young', 'Kim, Moon Jung', 'Seong, Yu Min', 'Lee, Wang Jun', 'Choe, Kang-Won', 'Kang, Yu Min', 'Lee, Baeckseung', 'Park, Sang-Joon']",J Korean Med Sci,,,True
ad3eea30652fd3de7debecd8a1c4723018a0a465,PMC,Translational recoding: canonical translation mechanisms reinterpreted,http://dx.doi.org/10.1093/nar/gkz783,PMC7026636,31511883,CC BY-NC,"During canonical translation, the ribosome moves along an mRNA from the start to the stop codon in exact steps of one codon at a time. The collinearity of the mRNA and the protein sequence is essential for the quality of the cellular proteome. Spontaneous errors in decoding or translocation are rare and result in a deficient protein. However, dedicated recoding signals in the mRNA can reprogram the ribosome to read the message in alternative ways. This review summarizes the recent advances in understanding the mechanisms of three types of recoding events: stop-codon readthrough, –1 ribosome frameshifting and translational bypassing. Recoding events provide insights into alternative modes of ribosome dynamics that are potentially applicable to other non-canonical modes of prokaryotic and eukaryotic translation.",2020 Feb 20,"['Rodnina, Marina V', 'Korniy, Natalia', 'Klimova, Mariia', 'Karki, Prajwal', 'Peng, Bee-Zen', 'Senyushkina, Tamara', 'Belardinelli, Riccardo', 'Maracci, Cristina', 'Wohlgemuth, Ingo', 'Samatova, Ekaterina', 'Peske, Frank']",Nucleic Acids Res,,,True
298a64fc7158cb78592bd96d53b4e58fbf562276,PMC,Co‐localization of Middle East respiratory syndrome coronavirus (MERS‐CoV) and dipeptidyl peptidase‐4 in the respiratory tract and lymphoid tissues of pigs and llamas,http://dx.doi.org/10.1111/tbed.13092,PMC7027813,30520548,CC BY-NC,"This study investigated the co‐localization of the Middle East respiratory syndrome coronavirus (MERS‐CoV) and its receptor dipeptidyl peptidase‐4 (DPP4) by immunohistochemistry (IHC) across respiratory and lymphoid organs of experimentally MERS‐CoV infected pigs and llamas. Also, scanning electron microscopy was performed to assess the ciliary integrity of respiratory epithelial cells in both species. In pigs, on day 2 post‐inoculation (p.i.), DPP4‐MERS‐CoV co‐localization was detected in medial turbinate epithelium. On day 4 p.i., the virus/receptor co‐localized in frontal and medial turbinate epithelial cells in pigs, and epithelial cells distributed unevenly through the whole nasal cavity and in the cervical lymph node in llamas. MERS‐CoV viral nucleocapsid was mainly detected in upper respiratory tract sites on days 2 and 4 p.i. in pigs and day 4 p.i. in llamas. No MERS‐CoV was detected on day 24 p.i. in any tissue by IHC. While pigs showed severe ciliary loss in the nasal mucosa both on days 2 and 4 p.i. and moderate loss in the trachea on days 4 and 24 p.i., ciliation of respiratory organs in llamas was not significantly affected. Obtained data confirm the role of DPP4 for MERS‐CoV entry in respiratory epithelial cells of llamas. Notably, several nasal epithelial cells in pigs were found to express viral antigen but not DPP4, suggesting the possible existence of other molecule/s facilitating virus entry or down regulation of DPP4 upon infection.",2019 Mar 28,"['Te, Nigeer', 'Vergara‐Alert, Júlia', 'Lehmbecker, Annika', 'Pérez, Mónica', 'Haagmans, Bart L.', 'Baumgärtner, Wolfgang', 'Bensaid, Albert', 'Segalés, Joaquim']",Transbound Emerg Dis,,,True
ca5a4a493d2bb7b970d36753a7eb36baf714a760,PMC,The importance of caveolins and caveolae to dermatology: Lessons from the caves and beyond,http://dx.doi.org/10.1111/exd.14068,PMC7028117,31845391,CC BY-NC,"Caveolae are flask‐shaped invaginations of the cell membrane rich in cholesterol and sphingomyelin, with caveolin proteins acting as their primary structural components that allow compartmentalization and orchestration of various signalling molecules. In this review, we discuss how pleiotropic functions of caveolin‐1 (Cav1) and its intricate roles in numerous cellular functions including lipid trafficking, signalling, cell migration and proliferation, as well as cellular senescence, infection and inflammation, are integral for normal development and functioning of skin and its appendages. We then examine how disruption of the homeostatic levels of Cav1 can lead to development of various cutaneous pathophysiologies including skin cancers, cutaneous fibroses, psoriasis, alopecia, age‐related changes in skin and aberrant wound healing and propose how levels of Cav1 may have theragnostic value in skin physiology/pathophysiology.",2020 Feb 10,"['Egger, Andjela N.', 'Rajabiestarabadi, Ali', 'Williams, Natalie M.', 'Resnik, Sydney R.', 'Fox, Joshua D.', 'Wong, Lulu L.', 'Jozic, Ivan']",Exp Dermatol,,,True
d82be8a4aaa62cde9678615d95b22163fa35c8dc,PMC,Fatal Primary Human Bocavirus Pneumonia in an Immunocompetent Adult,http://dx.doi.org/10.2169/internalmedicine.3583-19,PMC7028423,31588085,CC BY-NC-ND,"A 70-year-old woman was admitted to our hospital for dyspnea and a fever of 2 weeks duration. Chest imaging showed bilateral infiltration, and a rapid diagnostic test for influenza virus, Mycoplasma pneumoniae, Streptococcus pneumoniae, and Legionella spp. was negative. She was intubated and mechanically ventilated and underwent bronchoalveolar lavage. Bronchoalveolar lavage fluid yielded no significant pathogens, and the multiplex polymerase chain reaction test was positive only for human bocavirus. Specific antibodies against significant pathogens were not increased in paired sera, so we diagnosed her with primary human bocavirus pneumonia.",2020 Feb 1,"['Ishiguro, Takashi', 'Hirota, Shuko', 'Kobayashi, Yasuhito', 'Takano, Kenji', 'Kobayashi, Yoichi', 'Shimizu, Yoshihiko', 'Takayanagi, Noboru']",Intern Med,,,True
6b6a3e24c4812ea75232742d0fdd0a4020289ce6,PMC,An updated estimation of the risk of transmission of the novel coronavirus (2019-nCov),http://dx.doi.org/10.1016/j.idm.2020.02.001,PMC7029158,32099934,CC BY-NC-ND,"The basic reproduction number of an infectious agent is the average number of infections one case can generate over the course of the infectious period, in a naïve, uninfected population. It is well-known that the estimation of this number may vary due to several methodological issues, including different assumptions and choice of parameters, utilized models, used datasets and estimation period. With the spreading of the novel coronavirus (2019-nCoV) infection, the reproduction number has been found to vary, reflecting the dynamics of transmission of the coronavirus outbreak as well as the case reporting rate. Due to significant variations in the control strategies, which have been changing over time, and thanks to the introduction of detection technologies that have been rapidly improved, enabling to shorten the time from infection/symptoms onset to diagnosis, leading to faster confirmation of the new coronavirus cases, our previous estimations on the transmission risk of the 2019-nCoV need to be revised. By using time-dependent contact and diagnose rates, we refit our previously proposed dynamics transmission model to the data available until January 29th(,) 2020 and re-estimated the effective daily reproduction ratio that better quantifies the evolution of the interventions. We estimated when the effective daily reproduction ratio has fallen below 1 and when the epidemics will peak. Our updated findings suggest that the best measure is persistent and strict self-isolation. The epidemics will continue to grow, and can peak soon with the peak time depending highly on the public health interventions practically implemented.",2020 Feb 11,"['Tang, Biao', 'Bragazzi, Nicola Luigi', 'Li, Qian', 'Tang, Sanyi', 'Xiao, Yanni', 'Wu, Jianhong']",Infect Dis Model,,,False
1f2bfec9b985a04dc2645ceabc4e5e456a9ad9a5,PMC,The 2019 Novel Coronavirus: A Crown Jewel of Pandemics?,http://dx.doi.org/10.2478/jccm-2020-0013,PMC7029402,32104726,CC BY-NC-ND,,2020 Jan 31,"Azamfirei, Razvan",J Crit Care Med (Targu Mures),,,True
a20ac7b01ea008ea43804434b4dfba43d841f9cf,PMC,"Should, and how can, exercise be done during a coronavirus outbreak? An interview with Dr. Jeffrey A. Woods",http://dx.doi.org/10.1016/j.jshs.2020.01.005,PMC7031769,32099717,CC BY-NC-ND,,2020 Mar 4,"Zhu, Weimo",J Sport Health Sci,,,False
029440dede483511b869a1a8ac39a7b53e5cc22f,PMC,Wuhan coronavirus (2019-nCoV): The need to maintain regular physical activity while taking precautions,http://dx.doi.org/10.1016/j.jshs.2020.02.001,PMC7031771,32099716,CC BY-NC-ND,,2020 Mar 4,"['Chen, Peijie', 'Mao, Lijuan', 'Nassis, George P.', 'Harmer, Peter', 'Ainsworth, Barbara E.', 'Li, Fuzhong']",J Sport Health Sci,,,False
3965a2d31b31a317f72d0f08695060dbd6952f82,PMC,"Real-time forecasts of the COVID-19 epidemic in China from February 5th to February 24th, 2020",http://dx.doi.org/10.1016/j.idm.2020.02.002,PMC7033348,32110742,CC BY-NC-ND,"The initial cluster of severe pneumonia cases that triggered the COVID-19 epidemic was identified in Wuhan, China in December 2019. While early cases of the disease were linked to a wet market, human-to-human transmission has driven the rapid spread of the virus throughout China. The Chinese government has implemented containment strategies of city-wide lockdowns, screening at airports and train stations, and isolation of suspected patients; however, the cumulative case count keeps growing every day. The ongoing outbreak presents a challenge for modelers, as limited data are available on the early growth trajectory, and the epidemiological characteristics of the novel coronavirus are yet to be fully elucidated. We use phenomenological models that have been validated during previous outbreaks to generate and assess short-term forecasts of the cumulative number of confirmed reported cases in Hubei province, the epicenter of the epidemic, and for the overall trajectory in China, excluding the province of Hubei. We collect daily reported cumulative confirmed cases for the 2019-nCoV outbreak for each Chinese province from the National Health Commission of China. Here, we provide 5, 10, and 15 day forecasts for five consecutive days, February 5th through February 9th, with quantified uncertainty based on a generalized logistic growth model, the Richards growth model, and a sub-epidemic wave model. Our most recent forecasts reported here, based on data up until February 9, 2020, largely agree across the three models presented and suggest an average range of 7409–7496 additional confirmed cases in Hubei and 1128–1929 additional cases in other provinces within the next five days. Models also predict an average total cumulative case count between 37,415 and 38,028 in Hubei and 11,588–13,499 in other provinces by February 24, 2020. Mean estimates and uncertainty bounds for both Hubei and other provinces have remained relatively stable in the last three reporting dates (February 7th – 9th). We also observe that each of the models predicts that the epidemic has reached saturation in both Hubei and other provinces. Our findings suggest that the containment strategies implemented in China are successfully reducing transmission and that the epidemic growth has slowed in recent days.",2020 Feb 14,"['Roosa, K.', 'Lee, Y.', 'Luo, R.', 'Kirpich, A.', 'Rothenberg, R.', 'Hyman, J.M.', 'Yan, P.', 'Chowell, G.']",Infect Dis Model,,,False
9a27c99f125072894ab9db357b4ff8858a11203d,PMC,Viral Load Kinetics of SARS-CoV-2 Infection in First Two Patients in Korea,http://dx.doi.org/10.3346/jkms.2020.35.e86,PMC7036338,32080991,CC BY-NC,"As of February 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak started in China in December 2019 has been spreading in many countries in the world. With the numbers of confirmed cases are increasing, information on the epidemiologic investigation and clinical manifestation have been accumulated. However, data on viral load kinetics in confirmed cases are lacking. Here, we present the viral load kinetics of the first two confirmed patients with mild to moderate illnesses in Korea in whom distinct viral load kinetics are shown. This report suggests that viral load kinetics of SARS-CoV-2 may be different from that of previously reported other coronavirus infections such as SARS-CoV.",2020 Feb 20,"['Kim, Jin Yong', 'Ko, Jae-Hoon', 'Kim, Yeonjae', 'Kim, Yae-Jean', 'Kim, Jeong-Min', 'Chung, Yoon-Seok', 'Kim, Heui Man', 'Han, Myung-Guk', 'Kim, So Yeon', 'Chin, Bum Sik']",J Korean Med Sci,,,True
b5094dcef4e616a20092ca5e3a30d0e9369455fd,PMC,Virus Isolation from the First Patient with SARS-CoV-2 in Korea,http://dx.doi.org/10.3346/jkms.2020.35.e84,PMC7036342,32080990,CC BY-NC,Novel coronavirus (SARS-CoV-2) is found to cause a large outbreak started from Wuhan since December 2019 in China and SARS-CoV-2 infections have been reported with epidemiological linkage to China in 25 countries until now. We isolated SARS-CoV-2 from the oropharyngeal sample obtained from the patient with the first laboratory-confirmed SARS-CoV-2 infection in Korea. Cytopathic effects of SARS-CoV-2 in the Vero cell cultures were confluent 3 days after the first blind passage of the sample. Coronavirus was confirmed with spherical particle having a fringe reminiscent of crown on transmission electron microscopy. Phylogenetic analyses of whole genome sequences showed that it clustered with other SARS-CoV-2 reported from Wuhan.,2020 Feb 18,"['Park, Wan Beom', 'Kwon, Nak-Jung', 'Choi, Su-Jin', 'Kang, Chang Kyung', 'Choe, Pyoeng Gyun', 'Kim, Jin Yong', 'Yun, Jiyoung', 'Lee, Gir-Won', 'Seong, Moon-Woo', 'Kim, Nam Joong', 'Seo, Jeong-Sun', 'Oh, Myoung-don']",J Korean Med Sci,,,True
58be092086c74c58e9067121a6ba4836468e7ec3,PMC,Letter to the Editor: Case of the Index Patient Who Caused Tertiary Transmission of Coronavirus Disease 2019 in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Pneumonia Monitored by Quantitative RT-PCR,http://dx.doi.org/10.3346/jkms.2020.35.e88,PMC7036343,32080992,CC BY-NC,,2020 Feb 20,"Kim, Jin Yong",J Korean Med Sci,,,True
dd215aa15c6f212275cacf2f9db5c2e8d4145217,PMC,Success of Big Infectious Disease Reimbursement Policy in China,http://dx.doi.org/10.1177/0046958020907788,PMC7036499,32075479,CC BY-NC,"Big infectious diseases do harm to the whole society, and it is highly crucial to control them on time. The major purpose of this article is to theoretically demonstrate that the Chinese government’s intervention in large-scale infectious diseases is successful and efficient. Two potential strategies were considered: strategy 1 was infectious disease without government intervention, and strategy 2 was infectious disease with government intervention. By evolution model, this article illustrates the efficiency of big infectious disease reimbursement policy in China. Without government reimbursement, this article finds that high expenditures accelerate the disease infection. The number of infected persons decreases under big infectious disease reimbursement policy in China. The higher the treatment costs, the more important the government intervention. Big infectious disease reimbursement policy in China can serve as an efficient example to cope with big infectious diseases.",2020 Feb 20,"['Nie, Kun-xi', 'Wang, Chan', 'Li, Xin-wu']",Inquiry,,,True
5f3fc1bf0b828ea47a282433d84726eb5b25447c,PMC,2019-nCoV: Polite with children!,http://dx.doi.org/10.4081/pr.2020.8495,PMC7036705,,CC BY-NC,,2020 Feb 11,"['Caselli, Désirée', 'Aricò, Maurizio']",Pediatr Rep,,,True
140ab046d55c6618aa71fea9e48b7971a7e4b60e,PMC,Safety Assessment of a Hemp Extract using Genotoxicity and Oral Repeat-Dose Toxicity Studies in Sprague-Dawley Rats,http://dx.doi.org/10.1016/j.toxrep.2020.02.014,PMC7036713,32123668,CC BY-NC-ND,"Cannabinoids are extracted from Cannabis sativa L. and are used for a variety of medicinal purposes. Recently, there has been a focus on the cannabinoid Cannabidiol (CBD) and its potential benefits. This study investigated the safety of a proprietary extract of C. sativa, consisting of 9% hemp extract (of which 6.27% is CBD) and 91% olive oil. The mutagenic potential of the hemp extract was evaluated with the AMES assay inclusive of a hepatic drug metabolizing mix (S9) rich in CYP enzymes. The test article did not elicit evidence of bacterial mutagenicity. GLP compliant 14-day and a 90-day toxicity study were conducted. Olive oil was used as a control. The 90-day study had a 28-day recovery period. Treatments for the 14-day non-recovery range-finding study were 0, 1000, 2000 and 4000 mg test article/kg body weight (bw)/day for 14 days. There was a non-statistically significant (p > 0.05) decrease in body weights for the male and female rats receiving the test article. Hypoactivity, hyperactivity, reduced food consumption and piloerection were observed in the rats receiving 4000 mg test article/kg bw. Histopathology showed an increase in the size of liver cells (hypertrophy) around the central vein (centrilobular) in Groups 3 (3/10) and 4 (5/10) that correlated with increased liver weights. In the 90-day study, 8 groups of rats were dosed with 0, 200, 400 and 800 mg test article/kg bw/day. Groups 5 to 8 had a 28-day recovery. There were no test article-linked changes in clinical observations, physical examinations, Functional Observation Battery, ophthalmology, Motor Activity Assessment, hematology, clinical chemistries and macropathology (all groups). With the exception of the liver and adrenal gland, no test article-linked pathology was observed. For all rats receiving the test article, histopathology showed hypertrophy of liver cells around the central vein. The increase of liver weight is most likely caused by hypertrophy due to up-regulation of the hepatic drug metabolizing enzymes. The hepatocellular hypertrophy was completely reversed in 28 days and was not considered to be an adverse effect. Vacuolization of the adrenal zona fasciculata was observed in the control and 800 mg test article/kg bw groups. The vacuolization of the zona fasciculata was of the same incidence and severity in treatment and control male rats and correlated with an increased in the weights of the adrenal glands. In addition, a statistically significant increase (p<0.05) in adrenal-to-body weight ratios was observed for females receiving 800 mg test article/kg bw. This increase in adrenal-to-body weight ratio did not correlate with any of the pathology findings. The NOAEL for the test article is 800 mg/kg bw/day for female and 400 mg/kg bw/day for male Sprague Dawley rats.",2020 Feb 20,"['Dziwenka, Margitta', 'Coppock, Robert', 'Alexander, McCorkle', 'Palumbo, Eddie', 'Ramirez, Carlos', 'Lermer, Stephen']",Toxicol Rep,,,False
d7f54f3f478888e9b3f3571a391ce869f0eac789,PMC,Novel Coronavirus Pneumonia Outbreak in 2019: Computed Tomographic Findings in Two Cases,http://dx.doi.org/10.3348/kjr.2020.0078,PMC7039714,32056397,CC BY-NC,"Since the 2019 novel coronavirus (2019-nCoV or officially named by the World Health Organization as COVID-19) outbreak in Wuhan, Hubei Province, China in 2019, there have been a few reports of its imaging findings. Here, we report two confirmed cases of 2019-nCoV pneumonia with chest computed tomography findings of multiple regions of patchy consolidation and ground-glass opacities in both lungs. These findings were characteristically located along the bronchial bundle or subpleural lungs.",2020 Mar 11,"['Lin, Xiaoqi', 'Gong, Zhenyu', 'Xiao, Zuke', 'Xiong, Jingliang', 'Fan, Bing', 'Liu, Jiaqi']",Korean J Radiol,,,True
92b6e41df821c7c137bfa56339734cee1715df3d,PMC,Pneumonia Associated with 2019 Novel Coronavirus: Can Computed Tomographic Findings Help Predict the Prognosis of the Disease?,http://dx.doi.org/10.3348/kjr.2020.0096,PMC7039716,32056396,CC BY-NC,,2020 Mar 11,"Lee, Kyung Soo",Korean J Radiol,,,True
2c2f0107d55f1c770896c982d59e0bfa035fd4d7,PMC,Development of a one-run real-time PCR detection system for pathogens associated with porcine respiratory diseases,http://dx.doi.org/10.1292/jvms.19-0063,PMC7041981,31866601,CC BY-NC-ND,"The etiology of Porcine respiratory disease complex is complicated by infections with multiple pathogens, and multiple infections increase the difficulty in identifying the causal pathogen. In this present study, we developed a detection system of microbes from porcine respiratory by using TaqMan real-time PCR (referred to as Dempo-PCR) to screen a broad range of pathogens associated with porcine respiratory diseases in a single run. We selected 17 porcine respiratory pathogens (Actinobacillus pleuropneumoniae, Boldetella bronchiseptica, Haemophilus parasuis, Pasteurella multocida, Pasteurella multocida toxin, Streptococcus suis, Mycoplasma hyopneumoniae, Mycoplasma hyorhinis, Mycoplasma hyosynovie, porcine circovirus 2, pseudorabies virus, porcine cytomegalovirus, swine influenza A virus, porcine reproductive and respiratory virus US strain, EU strain, porcine respiratory coronavirus and porcine hemagglutinating encephalomyelitis virus) as detection targets and designed novel specific primer-probe sets for seven of them. In sensitivity test by using standard curves from synthesized DNA, all primer-probe sets showed high sensitivity. However, porcine reproductive and respiratory virus is known to have a high frequency of genetic mutations, and the primer and probe sequences will need to be checked at a considerable frequency when performing Dempo-PCR from field samples. A total of 30 lung samples from swine showing respiratory symptoms on six farms were tested by the Dempo-PCR to validate the assay’s clinical performance. As the results, 12 pathogens (5 virus and 7 bacteria) were detected and porcine reproductive and respiratory virus US strain, Mycoplasma hyorhinis, Haemophilus parasuis, and porcine cytomegalovirus were detected at high frequency. These results suggest that Dempo-PCR assay can be applied as a screening system with wide detection targets.",2020 Feb 23,"['SUNAGA, Fujiko', 'TSUCHIAKA, Shinobu', 'KISHIMOTO, Mai', 'AOKI, Hiroshi', 'KAKINOKI, Mari', 'KURE, Katsumasa', 'OKUMURA, Hanako', 'OKUMURA, Maho', 'OKUMURA, Atsushi', 'NAGAI, Makoto', 'OMATSU, Tsutomu', 'MIZUTANI, Tetsuya']",J Vet Med Sci,,,True
017015a89a8532f7b4a05bc06126d9e4413d2342,PMC,Development of a one-run real-time PCR detection system for pathogens associated with porcine respiratory diseases,http://dx.doi.org/10.1292/jvms.19-0063,PMC7041981,31866601,CC BY-NC-ND,"The etiology of Porcine respiratory disease complex is complicated by infections with multiple pathogens, and multiple infections increase the difficulty in identifying the causal pathogen. In this present study, we developed a detection system of microbes from porcine respiratory by using TaqMan real-time PCR (referred to as Dempo-PCR) to screen a broad range of pathogens associated with porcine respiratory diseases in a single run. We selected 17 porcine respiratory pathogens (Actinobacillus pleuropneumoniae, Boldetella bronchiseptica, Haemophilus parasuis, Pasteurella multocida, Pasteurella multocida toxin, Streptococcus suis, Mycoplasma hyopneumoniae, Mycoplasma hyorhinis, Mycoplasma hyosynovie, porcine circovirus 2, pseudorabies virus, porcine cytomegalovirus, swine influenza A virus, porcine reproductive and respiratory virus US strain, EU strain, porcine respiratory coronavirus and porcine hemagglutinating encephalomyelitis virus) as detection targets and designed novel specific primer-probe sets for seven of them. In sensitivity test by using standard curves from synthesized DNA, all primer-probe sets showed high sensitivity. However, porcine reproductive and respiratory virus is known to have a high frequency of genetic mutations, and the primer and probe sequences will need to be checked at a considerable frequency when performing Dempo-PCR from field samples. A total of 30 lung samples from swine showing respiratory symptoms on six farms were tested by the Dempo-PCR to validate the assay’s clinical performance. As the results, 12 pathogens (5 virus and 7 bacteria) were detected and porcine reproductive and respiratory virus US strain, Mycoplasma hyorhinis, Haemophilus parasuis, and porcine cytomegalovirus were detected at high frequency. These results suggest that Dempo-PCR assay can be applied as a screening system with wide detection targets.",2020 Feb 23,"['SUNAGA, Fujiko', 'TSUCHIAKA, Shinobu', 'KISHIMOTO, Mai', 'AOKI, Hiroshi', 'KAKINOKI, Mari', 'KURE, Katsumasa', 'OKUMURA, Hanako', 'OKUMURA, Maho', 'OKUMURA, Atsushi', 'NAGAI, Makoto', 'OMATSU, Tsutomu', 'MIZUTANI, Tetsuya']",J Vet Med Sci,,,False
9e90670ce5061438424bedfc1f400b75e3dea417,PMC,Role of brain renin angiotensin system in neurodegeneration: An update,http://dx.doi.org/10.1016/j.sjbs.2020.01.026,PMC7042626,32127770,CC BY-NC-ND,"Renin angiotensin system (RAS) is an endocrine system widely known for its physiological roles in electrolyte homeostasis, body fluid volume regulation and cardiovascular control in peripheral circulation. However, brain RAS is an independent form of RAS expressed locally in the brain, which is known to be involved in brain functions and disorders. There is strong evidence for a major involvement of excessive brain angiotensin converting enzyme (ACE)/Angiotensin II (Ang II)/Angiotensin type-1 receptor (AT-1R) axis in increased activation of oxidative stress, apoptosis and neuroinflammation causing neurodegeneration in several brain disorders. Numerous studies have demonstrated strong neuroprotective effects by blocking AT1R in these brain disorders. Additionally, the angiotensin converting enzyme 2 (ACE2)/Angiotensin (1–7)/Mas receptor (MASR), is another axis of brain RAS which counteracts the damaging effects of ACE/Ang II/AT1R axis on neurons in the brain. Thus, angiotensin II receptor blockers (ARBs) and activation of ACE2/Angiotensin (1–7)/MASR axis may serve as an exciting and novel method for neuroprotection in several neurodegenerative diseases. Here in this review article, we discuss the expression of RAS in the brain and highlight how altered RAS level may cause neurodegeneration. Understanding the pathophysiology of RAS and their links to neurodegeneration has enormous potential to identify potentially effective pharmacological tools to treat neurodegenerative diseases in the brain.",2020 Mar 30,"['Abiodun, Oyesiji A.', 'Ola, Mohammad Shamsul']",Saudi J Biol Sci,,,False
0c88aef176b70c6b11a51028124680237a6e5abd,PMC,Rapid Multiplex Testing for Upper Respiratory Pathogens in the Emergency Department: A Randomized Controlled Trial,http://dx.doi.org/10.1093/ofid/ofz481,PMC7043218,32128326,CC BY-NC-ND,"BACKGROUND: Acute upper respiratory tract infections are a common cause of emergency department (ED) visits and often result in unnecessary antibiotic treatment. METHODS: We conducted a randomized clinical trial to evaluate the impact of a rapid, multipathogen respiratory panel (RP) test vs usual care (control). Patients were eligible if they were ≥12 months old, had symptoms of upper respiratory infection or influenza-like illness, and were not on antibiotics. The primary outcome was antibiotic prescription; secondary outcomes included antiviral prescription, disposition, and length of stay (ClinicalTrials.gov# NCT02957136). RESULTS: Of 191 patients enrolled, 93 (49%) received RP testing; 98 (51%) received usual care. Fifty-three (57%) RP and 7 (7%) control patients had a virus detected and reported during the ED visit (P = .0001). Twenty (22%) RP patients and 33 (34%) usual care patients received antibiotics during the ED visit (–12%; 95% confidence interval, –25% to 0.4%; P = .06/0.08); 9 RP patients received antibiotics despite having a virus detected. The magnitude of antibiotic reduction was greater in children (–19%) vs adults (–9%, post hoc analysis). There was no difference in antiviral use, length of stay, or disposition. CONCLUSIONS: Rapid RP testing was associated with a trend toward decreased antibiotic use, suggesting a potential benefit from more rapid viral tests in the ED. Future studies should determine if specific groups are more likely to benefit from testing and evaluate the relative cost and effectiveness of broad testing, focused testing, and a combined diagnostic and antimicrobial stewardship approach.",2019 Nov 5,"['May, Larissa', 'Tatro, Grant', 'Poltavskiy, Eduard', 'Mooso, Benjamin', 'Hon, Simson', 'Bang, Heejung', 'Polage, Christopher']",Open Forum Infect Dis,,,True
948027e1ec13360c3967548ba0f45b50769dceaf,PMC,Rapid Multiplex Testing for Upper Respiratory Pathogens in the Emergency Department: A Randomized Controlled Trial,http://dx.doi.org/10.1093/ofid/ofz481,PMC7043218,32128326,CC BY-NC-ND,"BACKGROUND: Acute upper respiratory tract infections are a common cause of emergency department (ED) visits and often result in unnecessary antibiotic treatment. METHODS: We conducted a randomized clinical trial to evaluate the impact of a rapid, multipathogen respiratory panel (RP) test vs usual care (control). Patients were eligible if they were ≥12 months old, had symptoms of upper respiratory infection or influenza-like illness, and were not on antibiotics. The primary outcome was antibiotic prescription; secondary outcomes included antiviral prescription, disposition, and length of stay (ClinicalTrials.gov# NCT02957136). RESULTS: Of 191 patients enrolled, 93 (49%) received RP testing; 98 (51%) received usual care. Fifty-three (57%) RP and 7 (7%) control patients had a virus detected and reported during the ED visit (P = .0001). Twenty (22%) RP patients and 33 (34%) usual care patients received antibiotics during the ED visit (–12%; 95% confidence interval, –25% to 0.4%; P = .06/0.08); 9 RP patients received antibiotics despite having a virus detected. The magnitude of antibiotic reduction was greater in children (–19%) vs adults (–9%, post hoc analysis). There was no difference in antiviral use, length of stay, or disposition. CONCLUSIONS: Rapid RP testing was associated with a trend toward decreased antibiotic use, suggesting a potential benefit from more rapid viral tests in the ED. Future studies should determine if specific groups are more likely to benefit from testing and evaluate the relative cost and effectiveness of broad testing, focused testing, and a combined diagnostic and antimicrobial stewardship approach.",2019 Nov 5,"['May, Larissa', 'Tatro, Grant', 'Poltavskiy, Eduard', 'Mooso, Benjamin', 'Hon, Simson', 'Bang, Heejung', 'Polage, Christopher']",Open Forum Infect Dis,,,False
956f777cf3a26f2989c840cbb927ac552b95732e,PMC,Association of specific viral infections with childhood asthma exacerbations,http://dx.doi.org/10.1556/1646.10.2018.35,PMC7044566,32148899,CC BY-NC,"INTRODUCTION: Asthma exacerbations may occur due to a variety of triggers including respiratory viruses. The aim of this study was to determine the role of particular viral infections in asthma exacerbations in children. MATERIALS AND METHODS: The study was performed at Dr. Daneshvari Hospital Pediatric Emergency Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran between 2014 and 2015. A nasopharyngeal aspirate or swab was obtained from each patient during admission. All samples were maintained at 4 °C until submission to the virology laboratory and were tested for respiratory viruses by nucleic acid testing. RESULTS: A total of 60 patients with asthma exacerbations were recruited for this study. Of the 60 samples collected from the patients with acute asthma exacerbations, rhinovirus was detected in 12 patients (20%), respiratory syncytial virus in 5 (8%), adenovirus in 5 (8%), and influenza virus in 1 (1.6%). Respiratory pathogens were not detected in 37 (61%) samples. All the samples investigated showed single viral infection. CONCLUSIONS: To conclude, the most common viruses detected were rhinovirus followed by respiratory syncytial virus (RSV) and adenovirus. RSV was more commonly associated with more severe attacks. Both the study design (e.g., time of sampling, age of the patients, etc.) and also the method used for viral detection influence the frequency of detection of the respiratory viruses.",,"['Hassanzad, Maryam', 'Nadji, Seyed Alireza', 'Darougar, Sepideh', 'Tashayoie-Nejad, Sabereh', 'Boloursaz, Mohammad Reza', 'Mahdaviani, Seyed Alireza', 'Baghaie, Nooshin', 'Ghaffaripour, Hosseinali', 'Velayati, Ali Akbar']",Interv Med Appl Sci.; 11(1):17-20,,,True
9b1db58b45ac9db3de3c103db7e9de544c6c3eea,PMC,"Provider perspectives on general practice in Henan, China: a mixed-methods study",http://dx.doi.org/10.1136/bmjopen-2019-036240,PMC7044834,32019820,CC BY-NC,"OBJECTIVE: Since 2011 China’s central government has committed to establishing a new ‘general practitioner’ (GP)-centred primary care system. To this end there have been great efforts to train an additional 300 000 GPs by 2020. This paper examines the perspective of practitioners in Henan, China, regarding general practice. DESIGN: A mixed-methods approach using focus group discussions (FGD), and structured questionnaires. SETTING/PARTICIPANTS: Seven FGDs and responses to 1887 questionnaires included medical students, primary care doctors and GP residents in Henan. RESULTS: The three surveyed medical groups have some awareness of the attributes of general practice (eg, comprehensiveness, first contact and coordination), but often misinterpret what being a GP entails. Five themes were identified through the FGDs and tested quantitatively for their prevalence with structured questionnaires. First, the GPs’ role as a comprehensive care provider was (mis)interpreted as an ‘all-round doctor’. Second, the GP’s responsibility as the first point of care was understood in two conflicting ways: private personal doctors of the rich and the powerful or village doctors for common people. Third, referral was understood as simply guiding patients to appropriate departments within the hospital while the gatekeeping role was interpreted to involve GPs being peoples’ health protectors rather than being also gatekeepers of specialty services. Traditional Chinese medicine now further complicates the understanding of GPs. And lastly, the GPs’ main responsibility was considered to be public health work. CONCLUSION: The misunderstandings of the roles and responsibilities of GPs render problematic the policy foundation of China’s GP-centred primary care system. Pursuing the quantity of GPs on its own is meaningless, since the number needed depends on the delineated role of GPs. Top priority is to establish clarity about the GP role, which requires reforming the health delivery system to address issues with fragmented care, strategically taking into account the development of GPs with work delegation and substitution and providing more clarity on the distinction between general practice and public health.",2020 Feb 3,"['Zhu, Jiming', 'Ariana, Proochista']",BMJ Open,,,True
ff2461416a15e35f6befb112accdc1301f5a7724,PMC,"Provider perspectives on general practice in Henan, China: a mixed-methods study",http://dx.doi.org/10.1136/bmjopen-2019-036240,PMC7044834,32019820,CC BY-NC,"OBJECTIVE: Since 2011 China’s central government has committed to establishing a new ‘general practitioner’ (GP)-centred primary care system. To this end there have been great efforts to train an additional 300 000 GPs by 2020. This paper examines the perspective of practitioners in Henan, China, regarding general practice. DESIGN: A mixed-methods approach using focus group discussions (FGD), and structured questionnaires. SETTING/PARTICIPANTS: Seven FGDs and responses to 1887 questionnaires included medical students, primary care doctors and GP residents in Henan. RESULTS: The three surveyed medical groups have some awareness of the attributes of general practice (eg, comprehensiveness, first contact and coordination), but often misinterpret what being a GP entails. Five themes were identified through the FGDs and tested quantitatively for their prevalence with structured questionnaires. First, the GPs’ role as a comprehensive care provider was (mis)interpreted as an ‘all-round doctor’. Second, the GP’s responsibility as the first point of care was understood in two conflicting ways: private personal doctors of the rich and the powerful or village doctors for common people. Third, referral was understood as simply guiding patients to appropriate departments within the hospital while the gatekeeping role was interpreted to involve GPs being peoples’ health protectors rather than being also gatekeepers of specialty services. Traditional Chinese medicine now further complicates the understanding of GPs. And lastly, the GPs’ main responsibility was considered to be public health work. CONCLUSION: The misunderstandings of the roles and responsibilities of GPs render problematic the policy foundation of China’s GP-centred primary care system. Pursuing the quantity of GPs on its own is meaningless, since the number needed depends on the delineated role of GPs. Top priority is to establish clarity about the GP role, which requires reforming the health delivery system to address issues with fragmented care, strategically taking into account the development of GPs with work delegation and substitution and providing more clarity on the distinction between general practice and public health.",2020 Feb 3,"['Zhu, Jiming', 'Ariana, Proochista']",BMJ Open,,,True
260c92c2ef71bc901d75e0c915329544ec28906e,PMC,"Provider perspectives on general practice in Henan, China: a mixed-methods study",http://dx.doi.org/10.1136/bmjopen-2019-036240,PMC7044834,32019820,CC BY-NC,"OBJECTIVE: Since 2011 China’s central government has committed to establishing a new ‘general practitioner’ (GP)-centred primary care system. To this end there have been great efforts to train an additional 300 000 GPs by 2020. This paper examines the perspective of practitioners in Henan, China, regarding general practice. DESIGN: A mixed-methods approach using focus group discussions (FGD), and structured questionnaires. SETTING/PARTICIPANTS: Seven FGDs and responses to 1887 questionnaires included medical students, primary care doctors and GP residents in Henan. RESULTS: The three surveyed medical groups have some awareness of the attributes of general practice (eg, comprehensiveness, first contact and coordination), but often misinterpret what being a GP entails. Five themes were identified through the FGDs and tested quantitatively for their prevalence with structured questionnaires. First, the GPs’ role as a comprehensive care provider was (mis)interpreted as an ‘all-round doctor’. Second, the GP’s responsibility as the first point of care was understood in two conflicting ways: private personal doctors of the rich and the powerful or village doctors for common people. Third, referral was understood as simply guiding patients to appropriate departments within the hospital while the gatekeeping role was interpreted to involve GPs being peoples’ health protectors rather than being also gatekeepers of specialty services. Traditional Chinese medicine now further complicates the understanding of GPs. And lastly, the GPs’ main responsibility was considered to be public health work. CONCLUSION: The misunderstandings of the roles and responsibilities of GPs render problematic the policy foundation of China’s GP-centred primary care system. Pursuing the quantity of GPs on its own is meaningless, since the number needed depends on the delineated role of GPs. Top priority is to establish clarity about the GP role, which requires reforming the health delivery system to address issues with fragmented care, strategically taking into account the development of GPs with work delegation and substitution and providing more clarity on the distinction between general practice and public health.",2020 Feb 3,"['Zhu, Jiming', 'Ariana, Proochista']",BMJ Open,,,False
a3b5e995f19fca615af9084f08e562b563a74085,PMC,Impact of isolation on hospitalised patients who are infectious: systematic review with meta-analysis,http://dx.doi.org/10.1136/bmjopen-2019-030371,PMC7044903,32075820,CC BY-NC,"OBJECTIVE: To systematically review the literature exploring the impact of isolation on hospitalised patients who are infectious: psychological and non-psychological outcomes. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Embase, Medline and PsycINFO were searched from inception until December 2018. Reference lists and Google Scholar were also handsearched. RESULTS: Twenty-six papers published from database inception to December 2018 were reviewed. A wide range of psychological and non-psychological outcomes were reported. There was a marked trend for isolated patients to exhibit higher levels of depression, the pooled standardised mean difference being 1.28 (95% CI 0.47 to 2.09) and anxiety 1.45 (95% CI 0.56 to 2.34), although both had high levels of heterogeneity, and worse outcomes for a range of care-related factors but with significant variation. CONCLUSION: The review indicates that isolation to contain the risk of infection has negative consequences for segregated patients. Although strength of the evidence is weak, comprising primarily single-centre convenience samples, consistency of the effects may strengthen this conclusion. More research needs to be undertaken to examine this relationship and develop and test interventions to reduce the negative effects of isolation.",2020 Feb 18,"['Purssell, Edward', 'Gould, Dinah', 'Chudleigh, Jane']",BMJ Open,,,True
21a19241ff8c8602a9cd610ceea62e746a6493e2,PMC,Impact of isolation on hospitalised patients who are infectious: systematic review with meta-analysis,http://dx.doi.org/10.1136/bmjopen-2019-030371,PMC7044903,32075820,CC BY-NC,"OBJECTIVE: To systematically review the literature exploring the impact of isolation on hospitalised patients who are infectious: psychological and non-psychological outcomes. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Embase, Medline and PsycINFO were searched from inception until December 2018. Reference lists and Google Scholar were also handsearched. RESULTS: Twenty-six papers published from database inception to December 2018 were reviewed. A wide range of psychological and non-psychological outcomes were reported. There was a marked trend for isolated patients to exhibit higher levels of depression, the pooled standardised mean difference being 1.28 (95% CI 0.47 to 2.09) and anxiety 1.45 (95% CI 0.56 to 2.34), although both had high levels of heterogeneity, and worse outcomes for a range of care-related factors but with significant variation. CONCLUSION: The review indicates that isolation to contain the risk of infection has negative consequences for segregated patients. Although strength of the evidence is weak, comprising primarily single-centre convenience samples, consistency of the effects may strengthen this conclusion. More research needs to be undertaken to examine this relationship and develop and test interventions to reduce the negative effects of isolation.",2020 Feb 18,"['Purssell, Edward', 'Gould, Dinah', 'Chudleigh, Jane']",BMJ Open,,,True
f69a2530ff271d313fee4a8c4aa6d9975d2a1ae8,PMC,Impact of isolation on hospitalised patients who are infectious: systematic review with meta-analysis,http://dx.doi.org/10.1136/bmjopen-2019-030371,PMC7044903,32075820,CC BY-NC,"OBJECTIVE: To systematically review the literature exploring the impact of isolation on hospitalised patients who are infectious: psychological and non-psychological outcomes. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Embase, Medline and PsycINFO were searched from inception until December 2018. Reference lists and Google Scholar were also handsearched. RESULTS: Twenty-six papers published from database inception to December 2018 were reviewed. A wide range of psychological and non-psychological outcomes were reported. There was a marked trend for isolated patients to exhibit higher levels of depression, the pooled standardised mean difference being 1.28 (95% CI 0.47 to 2.09) and anxiety 1.45 (95% CI 0.56 to 2.34), although both had high levels of heterogeneity, and worse outcomes for a range of care-related factors but with significant variation. CONCLUSION: The review indicates that isolation to contain the risk of infection has negative consequences for segregated patients. Although strength of the evidence is weak, comprising primarily single-centre convenience samples, consistency of the effects may strengthen this conclusion. More research needs to be undertaken to examine this relationship and develop and test interventions to reduce the negative effects of isolation.",2020 Feb 18,"['Purssell, Edward', 'Gould, Dinah', 'Chudleigh, Jane']",BMJ Open,,,False
db7f377298ce92a409440604688c3b935bf7dd07,PMC,Impact of isolation on hospitalised patients who are infectious: systematic review with meta-analysis,http://dx.doi.org/10.1136/bmjopen-2019-030371,PMC7044903,32075820,CC BY-NC,"OBJECTIVE: To systematically review the literature exploring the impact of isolation on hospitalised patients who are infectious: psychological and non-psychological outcomes. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Embase, Medline and PsycINFO were searched from inception until December 2018. Reference lists and Google Scholar were also handsearched. RESULTS: Twenty-six papers published from database inception to December 2018 were reviewed. A wide range of psychological and non-psychological outcomes were reported. There was a marked trend for isolated patients to exhibit higher levels of depression, the pooled standardised mean difference being 1.28 (95% CI 0.47 to 2.09) and anxiety 1.45 (95% CI 0.56 to 2.34), although both had high levels of heterogeneity, and worse outcomes for a range of care-related factors but with significant variation. CONCLUSION: The review indicates that isolation to contain the risk of infection has negative consequences for segregated patients. Although strength of the evidence is weak, comprising primarily single-centre convenience samples, consistency of the effects may strengthen this conclusion. More research needs to be undertaken to examine this relationship and develop and test interventions to reduce the negative effects of isolation.",2020 Feb 18,"['Purssell, Edward', 'Gould, Dinah', 'Chudleigh, Jane']",BMJ Open,,,False
d0c5aa527f5ac0e80012380e5f40133e593e81ba,PMC,Impact of isolation on hospitalised patients who are infectious: systematic review with meta-analysis,http://dx.doi.org/10.1136/bmjopen-2019-030371,PMC7044903,32075820,CC BY-NC,"OBJECTIVE: To systematically review the literature exploring the impact of isolation on hospitalised patients who are infectious: psychological and non-psychological outcomes. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Embase, Medline and PsycINFO were searched from inception until December 2018. Reference lists and Google Scholar were also handsearched. RESULTS: Twenty-six papers published from database inception to December 2018 were reviewed. A wide range of psychological and non-psychological outcomes were reported. There was a marked trend for isolated patients to exhibit higher levels of depression, the pooled standardised mean difference being 1.28 (95% CI 0.47 to 2.09) and anxiety 1.45 (95% CI 0.56 to 2.34), although both had high levels of heterogeneity, and worse outcomes for a range of care-related factors but with significant variation. CONCLUSION: The review indicates that isolation to contain the risk of infection has negative consequences for segregated patients. Although strength of the evidence is weak, comprising primarily single-centre convenience samples, consistency of the effects may strengthen this conclusion. More research needs to be undertaken to examine this relationship and develop and test interventions to reduce the negative effects of isolation.",2020 Feb 18,"['Purssell, Edward', 'Gould, Dinah', 'Chudleigh, Jane']",BMJ Open,,,False
b10f86263a762361a88a50eaa0b8f2640551874d,PMC,Impact of isolation on hospitalised patients who are infectious: systematic review with meta-analysis,http://dx.doi.org/10.1136/bmjopen-2019-030371,PMC7044903,32075820,CC BY-NC,"OBJECTIVE: To systematically review the literature exploring the impact of isolation on hospitalised patients who are infectious: psychological and non-psychological outcomes. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Embase, Medline and PsycINFO were searched from inception until December 2018. Reference lists and Google Scholar were also handsearched. RESULTS: Twenty-six papers published from database inception to December 2018 were reviewed. A wide range of psychological and non-psychological outcomes were reported. There was a marked trend for isolated patients to exhibit higher levels of depression, the pooled standardised mean difference being 1.28 (95% CI 0.47 to 2.09) and anxiety 1.45 (95% CI 0.56 to 2.34), although both had high levels of heterogeneity, and worse outcomes for a range of care-related factors but with significant variation. CONCLUSION: The review indicates that isolation to contain the risk of infection has negative consequences for segregated patients. Although strength of the evidence is weak, comprising primarily single-centre convenience samples, consistency of the effects may strengthen this conclusion. More research needs to be undertaken to examine this relationship and develop and test interventions to reduce the negative effects of isolation.",2020 Feb 18,"['Purssell, Edward', 'Gould, Dinah', 'Chudleigh, Jane']",BMJ Open,,,False
85d5d7886d7ad0ec2c28a5ca133853c64a1733ed,PMC,Impact of isolation on hospitalised patients who are infectious: systematic review with meta-analysis,http://dx.doi.org/10.1136/bmjopen-2019-030371,PMC7044903,32075820,CC BY-NC,"OBJECTIVE: To systematically review the literature exploring the impact of isolation on hospitalised patients who are infectious: psychological and non-psychological outcomes. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Embase, Medline and PsycINFO were searched from inception until December 2018. Reference lists and Google Scholar were also handsearched. RESULTS: Twenty-six papers published from database inception to December 2018 were reviewed. A wide range of psychological and non-psychological outcomes were reported. There was a marked trend for isolated patients to exhibit higher levels of depression, the pooled standardised mean difference being 1.28 (95% CI 0.47 to 2.09) and anxiety 1.45 (95% CI 0.56 to 2.34), although both had high levels of heterogeneity, and worse outcomes for a range of care-related factors but with significant variation. CONCLUSION: The review indicates that isolation to contain the risk of infection has negative consequences for segregated patients. Although strength of the evidence is weak, comprising primarily single-centre convenience samples, consistency of the effects may strengthen this conclusion. More research needs to be undertaken to examine this relationship and develop and test interventions to reduce the negative effects of isolation.",2020 Feb 18,"['Purssell, Edward', 'Gould, Dinah', 'Chudleigh, Jane']",BMJ Open,,,False
ba77e9c0b7ae7296c3bf89b2cda28bc28819bb6e,PMC,Impact of isolation on hospitalised patients who are infectious: systematic review with meta-analysis,http://dx.doi.org/10.1136/bmjopen-2019-030371,PMC7044903,32075820,CC BY-NC,"OBJECTIVE: To systematically review the literature exploring the impact of isolation on hospitalised patients who are infectious: psychological and non-psychological outcomes. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Embase, Medline and PsycINFO were searched from inception until December 2018. Reference lists and Google Scholar were also handsearched. RESULTS: Twenty-six papers published from database inception to December 2018 were reviewed. A wide range of psychological and non-psychological outcomes were reported. There was a marked trend for isolated patients to exhibit higher levels of depression, the pooled standardised mean difference being 1.28 (95% CI 0.47 to 2.09) and anxiety 1.45 (95% CI 0.56 to 2.34), although both had high levels of heterogeneity, and worse outcomes for a range of care-related factors but with significant variation. CONCLUSION: The review indicates that isolation to contain the risk of infection has negative consequences for segregated patients. Although strength of the evidence is weak, comprising primarily single-centre convenience samples, consistency of the effects may strengthen this conclusion. More research needs to be undertaken to examine this relationship and develop and test interventions to reduce the negative effects of isolation.",2020 Feb 18,"['Purssell, Edward', 'Gould, Dinah', 'Chudleigh, Jane']",BMJ Open,,,False
6fc52ed878c271020a2a375bb6e4b12943a7666c,PMC,Effectiveness for the Response to COVID-19: The MERS Outbreak Containment Procedures,http://dx.doi.org/10.24171/j.phrp.2020.11.1.01,PMC7045877,32149035,CC BY-NC-ND,,2020 Feb,"Cho, Hae-Wol",Osong Public Health Res Perspect,,,False
b9c4627fca08e4d363dbd7c27da40834a048a262,PMC,Early Epidemiological and Clinical Characteristics of 28 Cases of Coronavirus Disease in South Korea,http://dx.doi.org/10.24171/j.phrp.2020.11.1.03,PMC7045878,32149037,CC BY-NC-ND,"OBJECTIVES: The first confirmed case of coronavirus disease 2019 (COVID-19) in South Korea was reported in January 2020, with 28 confirmed cases reported as of February 14(th), 2020. The epidemiological and clinical characteristics of all 28 cases were analyzed in response to this disease. METHODS: The epidemiological characteristics and early clinical features of the 28 patients from Korea with confirmed COVID-19 were analyzed using COVID-19 reporting and surveillance data and the epidemiological investigation reports prepared by the rapid response team. RESULTS: There were 16 patients that entered Korea from foreign countries: Wuhan, China (11 patients), Zhuhai, China, (1 patient), Singapore (2 patients), Japan (1 patient), and Thailand (1 patient). The early symptoms were fever, sore throat, cough or sputum production, chills, and muscle ache. Three patients were asymptomatic, however, 18 developed pneumonia. Of the 28 cases, 16 were index cases imported from abroad, with 10 cases of secondary infection originating in Korea, and the route of transmission still under investigation for 2 patients. The 10 patients with secondary infection were infected from contact with family members or acquaintances of primary patients, and the suspected sites of transmission were mostly at home. CONCLUSION: COVID-19 in Korea was spread by 16 infected individuals traveling from other countries, leading to second-generation cases. The initial symptoms were mostly minor, but the disease was infectious at this stage, resulting from close contact, particularly at home. Establishing an early detection strategy for COVID-19 is crucial for managing the transmission of the disease.",2020 Feb,,Osong Public Health Res Perspect,,,True
90b31a2542e2275640ec9dc8264cdf1e975d807e,PMC,Identification of Coronavirus Isolated from a Patient in Korea with COVID-19,http://dx.doi.org/10.24171/j.phrp.2020.11.1.02,PMC7045880,32149036,CC BY-NC-ND,"OBJECTIVES: Following reports of patients with unexplained pneumonia at the end of December 2019 in Wuhan, China, the causative agent was identified as coronavirus (SARS-CoV-2), and the 2019 novel coronavirus disease was named COVID-19 by the World Health Organization. Putative patients with COVID-19 have been identified in South Korea, and attempts have been made to isolate the pathogen from these patients. METHODS: Upper and lower respiratory tract secretion samples from putative patients with COVID-19 were inoculated onto cells to isolate the virus. Full genome sequencing and electron microscopy were used to identify the virus. RESULTS: The virus replicated in Vero cells and cytopathic effects were observed. Full genome sequencing showed that the virus genome exhibited sequence homology of more than 99.9% with SARS-CoV-2 which was isolated from patients from other countries, for instance China. Sequence homology of SARS-CoV-2 with SARS-CoV, and MERS-CoV was 77.5% and 50%, respectively. Coronavirus-specific morphology was observed by electron microscopy in virus-infected Vero cells. CONCLUSION: SARS-CoV-2 was isolated from putative patients with unexplained pneumonia and intermittent coughing and fever. The isolated virus was named BetaCoV/Korea/KCDC03/2020.",2020 Feb,"['Kim, Jeong-Min', 'Chung, Yoon-Seok', 'Jo, Hye Jun', 'Lee, Nam-Joo', 'Kim, Mi Seon', 'Woo, Sang Hee', 'Park, Sehee', 'Kim, Jee Woong', 'Kim, Heui Man', 'Han, Myung-Guk']",Osong Public Health Res Perspect,,,True
5644db6f53b8425eedbdb33ae2c8924e02cdf447,PMC,Contact Transmission of COVID-19 in South Korea: Novel Investigation Techniques for Tracing Contacts,http://dx.doi.org/10.24171/j.phrp.2020.11.1.09,PMC7045882,32149043,CC BY-NC-ND,"In the epidemiological investigation of an infectious disease, investigating, classifying, tracking, and managing contacts by identifying the patient’s route are important for preventing further transmission of the disease. However, omissions and errors in previous activities can occur when the investigation is performed through only a proxy interview with the patient. To overcome these limitations, methods that can objectively verify the patient’s claims (medical facility records, Global Positioning System, card transactions, and closed-circuit television) were used for the recent ongoing coronavirus disease 2019 contact investigations in South Korea.",2020 Feb,,Osong Public Health Res Perspect,,,True
35166631ae0d6093844d32f88e663fc1dbf8b415,PMC,Challenges and responsibilities of family doctors in the new global coronavirus outbreak,http://dx.doi.org/10.1136/fmch-2020-000333,PMC7046369,32148740,CC BY-NC,,2020 Feb 21,"Li, Donald Kwok Tung",Fam Med Community Health,,,False
3b8d650d6325394ab80ca6c41330f625134680eb,PMC,A Novel Approach of Consultation on 2019 Novel Coronavirus (COVID-19)-Related Psychological and Mental Problems: Structured Letter Therapy,http://dx.doi.org/10.30773/pi.2020.0047,PMC7047000,32093461,CC BY-NC,,2020 Feb 25,"Xiao, Chunfeng",Psychiatry Investig,,,True
9b18c2064a44deefb8f0975a3309d6e5cbf97c36,PMC,Mental Health Care Measures in Response to the 2019 Novel Coronavirus Outbreak in Korea,http://dx.doi.org/10.30773/pi.2020.0058,PMC7047003,32093458,CC BY-NC,,2020 Feb 25,"['Park, Seon-Cheol', 'Park, Yong Chon']",Psychiatry Investig,,,True
b399adcfb1d563f2c836e2c924fb0c090fca961a,PMC,Effect of acute respiratory infections in infancy on pulmonary function test at 3 years of age: a prospective birth cohort study,http://dx.doi.org/10.1136/bmjresp-2019-000436,PMC7047475,32079606,CC BY-NC,"INTRODUCTION: Acute respiratory infections (ARIs) in infancy may have a long-term impact on the developing respiratory system. We planned a prospective cohort study to determine the impact of ARI during infancy on the pulmonary function test indices at 3 years of age. METHODS: A cohort of normal, full-term newborns were followed up 6 monthly and during ARI episodes. Infant pulmonary function tests (IPFTs) were performed at baseline and each follow-up visit using tidal breathing flow-volume loop, rapid thoracoabdominal compression (RTC) and raised volume RTC manoeuvres. During each ARI episode, nasopharyngeal aspirates were tested for respiratory pathogens by real-time PCR. RESULTS: We screened 3421 neonates; 310 were enrolled; IPFT was performed in 225 (boys: 125 (55.6%)) at 3 years. During infancy, 470 ARI episodes were documented in 173 infants. At 3 years, children with history of any ARI episode during infancy had lower forced expiratory volume in 1 s (FEV(1.0)), forced expiratory volume in 0.75 s (FEV(0.75)), forced expiratory volume in 0.5 s (FEV(0.5)), forced expiratory flow between 25% and 75% of FVC (FEF(25–75)), and maximal expiratory flow at 25% of FVC (MEF(25)) as compared with those without any ARI episode during infancy. The ratio of tidal expiratory flow (TEF) at 25% or 50% of tidal expiratory volume to peak TEF (TEF(50) or TEF(25)/peak TEF) at 3 years was significantly increased in children who had ARI in infancy. CONCLUSIONS: ARI during infancy is associated with impaired pulmonary function indices such as increased resistance and decreased forced expiratory flow and volume at 3 years of age.",2020 Feb 19,"['Kumar, Prawin', 'Mukherjee, Aparna', 'Randev, Shivani', 'Medigeshi, Guruprasad R', 'Jat, Kana Ram', 'Kapil, Arti', 'Lodha, Rakesh', 'Kabra, Sushil Kumar']",BMJ Open Respir Res,,,True
f3c42fe2e4ec58780e78b0197b09e1ef615d27b6,PMC,Effect of acute respiratory infections in infancy on pulmonary function test at 3 years of age: a prospective birth cohort study,http://dx.doi.org/10.1136/bmjresp-2019-000436,PMC7047475,32079606,CC BY-NC,"INTRODUCTION: Acute respiratory infections (ARIs) in infancy may have a long-term impact on the developing respiratory system. We planned a prospective cohort study to determine the impact of ARI during infancy on the pulmonary function test indices at 3 years of age. METHODS: A cohort of normal, full-term newborns were followed up 6 monthly and during ARI episodes. Infant pulmonary function tests (IPFTs) were performed at baseline and each follow-up visit using tidal breathing flow-volume loop, rapid thoracoabdominal compression (RTC) and raised volume RTC manoeuvres. During each ARI episode, nasopharyngeal aspirates were tested for respiratory pathogens by real-time PCR. RESULTS: We screened 3421 neonates; 310 were enrolled; IPFT was performed in 225 (boys: 125 (55.6%)) at 3 years. During infancy, 470 ARI episodes were documented in 173 infants. At 3 years, children with history of any ARI episode during infancy had lower forced expiratory volume in 1 s (FEV(1.0)), forced expiratory volume in 0.75 s (FEV(0.75)), forced expiratory volume in 0.5 s (FEV(0.5)), forced expiratory flow between 25% and 75% of FVC (FEF(25–75)), and maximal expiratory flow at 25% of FVC (MEF(25)) as compared with those without any ARI episode during infancy. The ratio of tidal expiratory flow (TEF) at 25% or 50% of tidal expiratory volume to peak TEF (TEF(50) or TEF(25)/peak TEF) at 3 years was significantly increased in children who had ARI in infancy. CONCLUSIONS: ARI during infancy is associated with impaired pulmonary function indices such as increased resistance and decreased forced expiratory flow and volume at 3 years of age.",2020 Feb 19,"['Kumar, Prawin', 'Mukherjee, Aparna', 'Randev, Shivani', 'Medigeshi, Guruprasad R', 'Jat, Kana Ram', 'Kapil, Arti', 'Lodha, Rakesh', 'Kabra, Sushil Kumar']",BMJ Open Respir Res,,,False
d56dbc061a440a3d5024e4574907e16669aa29ae,PMC,Effect of acute respiratory infections in infancy on pulmonary function test at 3 years of age: a prospective birth cohort study,http://dx.doi.org/10.1136/bmjresp-2019-000436,PMC7047475,32079606,CC BY-NC,"INTRODUCTION: Acute respiratory infections (ARIs) in infancy may have a long-term impact on the developing respiratory system. We planned a prospective cohort study to determine the impact of ARI during infancy on the pulmonary function test indices at 3 years of age. METHODS: A cohort of normal, full-term newborns were followed up 6 monthly and during ARI episodes. Infant pulmonary function tests (IPFTs) were performed at baseline and each follow-up visit using tidal breathing flow-volume loop, rapid thoracoabdominal compression (RTC) and raised volume RTC manoeuvres. During each ARI episode, nasopharyngeal aspirates were tested for respiratory pathogens by real-time PCR. RESULTS: We screened 3421 neonates; 310 were enrolled; IPFT was performed in 225 (boys: 125 (55.6%)) at 3 years. During infancy, 470 ARI episodes were documented in 173 infants. At 3 years, children with history of any ARI episode during infancy had lower forced expiratory volume in 1 s (FEV(1.0)), forced expiratory volume in 0.75 s (FEV(0.75)), forced expiratory volume in 0.5 s (FEV(0.5)), forced expiratory flow between 25% and 75% of FVC (FEF(25–75)), and maximal expiratory flow at 25% of FVC (MEF(25)) as compared with those without any ARI episode during infancy. The ratio of tidal expiratory flow (TEF) at 25% or 50% of tidal expiratory volume to peak TEF (TEF(50) or TEF(25)/peak TEF) at 3 years was significantly increased in children who had ARI in infancy. CONCLUSIONS: ARI during infancy is associated with impaired pulmonary function indices such as increased resistance and decreased forced expiratory flow and volume at 3 years of age.",2020 Feb 19,"['Kumar, Prawin', 'Mukherjee, Aparna', 'Randev, Shivani', 'Medigeshi, Guruprasad R', 'Jat, Kana Ram', 'Kapil, Arti', 'Lodha, Rakesh', 'Kabra, Sushil Kumar']",BMJ Open Respir Res,,,False
86187e3b53204c29186866ed157cbe911d94a1a1,PMC,Effect of acute respiratory infections in infancy on pulmonary function test at 3 years of age: a prospective birth cohort study,http://dx.doi.org/10.1136/bmjresp-2019-000436,PMC7047475,32079606,CC BY-NC,"INTRODUCTION: Acute respiratory infections (ARIs) in infancy may have a long-term impact on the developing respiratory system. We planned a prospective cohort study to determine the impact of ARI during infancy on the pulmonary function test indices at 3 years of age. METHODS: A cohort of normal, full-term newborns were followed up 6 monthly and during ARI episodes. Infant pulmonary function tests (IPFTs) were performed at baseline and each follow-up visit using tidal breathing flow-volume loop, rapid thoracoabdominal compression (RTC) and raised volume RTC manoeuvres. During each ARI episode, nasopharyngeal aspirates were tested for respiratory pathogens by real-time PCR. RESULTS: We screened 3421 neonates; 310 were enrolled; IPFT was performed in 225 (boys: 125 (55.6%)) at 3 years. During infancy, 470 ARI episodes were documented in 173 infants. At 3 years, children with history of any ARI episode during infancy had lower forced expiratory volume in 1 s (FEV(1.0)), forced expiratory volume in 0.75 s (FEV(0.75)), forced expiratory volume in 0.5 s (FEV(0.5)), forced expiratory flow between 25% and 75% of FVC (FEF(25–75)), and maximal expiratory flow at 25% of FVC (MEF(25)) as compared with those without any ARI episode during infancy. The ratio of tidal expiratory flow (TEF) at 25% or 50% of tidal expiratory volume to peak TEF (TEF(50) or TEF(25)/peak TEF) at 3 years was significantly increased in children who had ARI in infancy. CONCLUSIONS: ARI during infancy is associated with impaired pulmonary function indices such as increased resistance and decreased forced expiratory flow and volume at 3 years of age.",2020 Feb 19,"['Kumar, Prawin', 'Mukherjee, Aparna', 'Randev, Shivani', 'Medigeshi, Guruprasad R', 'Jat, Kana Ram', 'Kapil, Arti', 'Lodha, Rakesh', 'Kabra, Sushil Kumar']",BMJ Open Respir Res,,,False
ce5237e4f58fd922034f51ad50d86057a4acf994,PMC,The novel Coronavirus (SARS-CoV-2) is a one health issue,http://dx.doi.org/10.1016/j.onehlt.2020.100123,PMC7049657,32140538,CC BY-NC-ND,,2020 Feb 14,"['Marty, Aileen Maria', 'Jones, Malcolm K.']",One Health,,,False
8cfe567d42fa459cb4364e240ddfe29629d03f85,PMC,The profile of respiratory pathogens in induced sputum of elderly and non-elderly asthmatics,http://dx.doi.org/10.5114/ceji.2019.92790,PMC7050048,32140050,CC BY-NC-SA,"INTRODUCTION: Respiratory pathogens are thought to be involved in the pathogenesis and exacerbations of asthma at all ages; however, little is known about the airway microbiome in the elderly. AIM OF THE STUDY: To identify respiratory pathogens in the induced sputum (IS) of elderly asthmatics, and to determine the association between pathogens and the markers of asthma activity. MATERIAL AND METHODS: Twenty-nine subjects with stable asthma, 15 above 65 years of age and 14 aged 30-49 years, underwent clinical evaluation, fractional exhaled nitric oxide measurement, and sputum induction. Pathogens were detected by multiplex reverse transcription polymerase chain reaction. The periostin concentration of IS supernatants was measured by enzyme-linked immunosorbent assay. Serum eosinophil cationic protein and total IgE levels were measured by Immun<sup>o</sup>CAP. RESULTS: Elderly patients, as compared to non-elderly, had significantly higher eosinophilia in IS, although other markers of eosinophilic inflammation were comparable. Half of the subjects were positive for Haemophilus influenzae. Chlamydophila pneumoniae was found in two subjects. Respiratory viruses were detected in more than 70% of patients. The detection rates and profiles of atypical bacteria and respiratory viruses were similar in both groups. Only in the elderly asthmatics was influenza A positivity associated with lower predicted FVC%, RSV A positivity connected with decreased tIgE concentration, and RSV B positivity related to a lower percentage of lymphocytes in IS. CONCLUSIONS: Despite the existence of differences in some clinical and inflammatory characteristics of asthma between elderly and non-elderly asthmatics, the pathogen detection rates in the IS from the two groups are similar.",2019 Jan 20,"['WARDZYŃSKA, ALEKSANDRA', 'PAWEŁCZYK, MAŁGORZATA', 'GŁOBIŃSKA, ANNA', 'MAKOWSKA, JOANNA S.', 'KOWALSKI, MAREK L.']",Cent Eur J Immunol,,,True
618a793838421a7bf238e8f6ae2635ca3d2f5a25,PMC,Regulation of Nucleotide Metabolism and Germline Proliferation in Response to Nucleotide Imbalance and Genotoxic Stresses by EndoU Nuclease,http://dx.doi.org/10.1016/j.celrep.2020.01.050,PMC7050212,32049015,CC BY-NC-ND,"Nucleotide deprivation and imbalance present detrimental conditions for animals and are thus expected to trigger cellular responses that direct protective changes in metabolic, developmental, and behavioral programs, albeit such mechanisms are vastly underexplored. Following our previous finding that Caenorhabditis elegans shut down germ cell proliferation in response to pyrimidine deprivation, we find in this study that endonuclease ENDU-2 regulates nucleotide metabolism and germ cell proliferation in response to nucleotide imbalance and other genotoxic stress, and that it affects mitotic chromosomal segregation in the intestine and lifespan. ENDU-2 expression is induced by nucleotide imbalance and genotoxic stress, and ENDU-2 exerts its function in the intestine, mostly by inhibiting the phosphorylation of CTPS-1 through repressing the PKA pathway and histone deacetylase HDA-1. Human EndoU also affects the response to genotoxic drugs. Our work reveals an unknown role of ENDU-2 in regulating nucleotide metabolism and animals’ response to genotoxic stress, which may link EndoU function to cancer treatment.",2020 Feb 11,"['Jia, Fan', 'Chi, Congwu', 'Han, Min']",Cell Rep,,,True
c1c96aa5875001fc787fe897c13a379514971fc1,PMC,Regulation of Nucleotide Metabolism and Germline Proliferation in Response to Nucleotide Imbalance and Genotoxic Stresses by EndoU Nuclease,http://dx.doi.org/10.1016/j.celrep.2020.01.050,PMC7050212,32049015,CC BY-NC-ND,"Nucleotide deprivation and imbalance present detrimental conditions for animals and are thus expected to trigger cellular responses that direct protective changes in metabolic, developmental, and behavioral programs, albeit such mechanisms are vastly underexplored. Following our previous finding that Caenorhabditis elegans shut down germ cell proliferation in response to pyrimidine deprivation, we find in this study that endonuclease ENDU-2 regulates nucleotide metabolism and germ cell proliferation in response to nucleotide imbalance and other genotoxic stress, and that it affects mitotic chromosomal segregation in the intestine and lifespan. ENDU-2 expression is induced by nucleotide imbalance and genotoxic stress, and ENDU-2 exerts its function in the intestine, mostly by inhibiting the phosphorylation of CTPS-1 through repressing the PKA pathway and histone deacetylase HDA-1. Human EndoU also affects the response to genotoxic drugs. Our work reveals an unknown role of ENDU-2 in regulating nucleotide metabolism and animals’ response to genotoxic stress, which may link EndoU function to cancer treatment.",2020 Feb 11,"['Jia, Fan', 'Chi, Congwu', 'Han, Min']",Cell Rep,,,False
4ebe630a2d802a7d6f2402a88c3dc88e7497dcfd,PMC,Regulation of Nucleotide Metabolism and Germline Proliferation in Response to Nucleotide Imbalance and Genotoxic Stresses by EndoU Nuclease,http://dx.doi.org/10.1016/j.celrep.2020.01.050,PMC7050212,32049015,CC BY-NC-ND,"Nucleotide deprivation and imbalance present detrimental conditions for animals and are thus expected to trigger cellular responses that direct protective changes in metabolic, developmental, and behavioral programs, albeit such mechanisms are vastly underexplored. Following our previous finding that Caenorhabditis elegans shut down germ cell proliferation in response to pyrimidine deprivation, we find in this study that endonuclease ENDU-2 regulates nucleotide metabolism and germ cell proliferation in response to nucleotide imbalance and other genotoxic stress, and that it affects mitotic chromosomal segregation in the intestine and lifespan. ENDU-2 expression is induced by nucleotide imbalance and genotoxic stress, and ENDU-2 exerts its function in the intestine, mostly by inhibiting the phosphorylation of CTPS-1 through repressing the PKA pathway and histone deacetylase HDA-1. Human EndoU also affects the response to genotoxic drugs. Our work reveals an unknown role of ENDU-2 in regulating nucleotide metabolism and animals’ response to genotoxic stress, which may link EndoU function to cancer treatment.",2020 Feb 11,"['Jia, Fan', 'Chi, Congwu', 'Han, Min']",Cell Rep,,,True
b1a61e5a2eee47ec7d39715451c05879d11a5de0,PMC,Vector control in Zika-affected communities: Local views on community engagement and public health ethics during outbreaks,http://dx.doi.org/10.1016/j.pmedr.2020.101059,PMC7052511,,CC BY-NC-ND,"Aerial spraying of products to kill larvae or adult mosquitoes is a public health measure used to control vector-borne diseases. In some outbreaks, the intervention has evoked controversy and community resistance. This study evaluated how local opinion leaders in US localities affected by Zika think about community engagement in public health policies for outbreak response. In December 2017 through March 2018, 4 focus groups were convened in Houston, TX, New Orleans, LA, Miami, FL, and Brooklyn, NY. They discussed a hypothetical scenario that featured vector control by aerial spraying. Participants (N = 20) more readily accepted this vector control method under 4 conditions: They were informed of alternatives, benefits, and risks for human health and the environment. Public health claims were backed by objective evidence and an authority figure genuinely working in the community’s interests. They received timely notice about how to mitigate toxin exposure. And, aerial spraying helped to protect vulnerable individuals. The community engagement requirements of the local opinion leaders resonate with core principles of recent public health ethics frameworks: namely, personal autonomy, transparency, reasonableness, and solidarity. Participants foresaw problems with community consent in an era of growing social media use and mistrust in governmental and scientific authority. They also debated whether health authorities should use moral-based arguments, in addition to science-based ones, to communicate aerial spraying’s risks and benefits.",2020 Jan 25,"['Schoch-Spana, Monica', 'Watson, Crystal', 'Ravi, Sanjana', 'Meyer, Diane', 'Pechta, Laura E.', 'Rose, Dale A.', 'Lubell, Keri M.', 'Podgornik, Michelle N.', 'Sell, Tara Kirk']",Prev Med Rep,,,False
6931b5e9ff438fd47df998904ce32f6f027514e8,PMC,Fear can be more harmful than the severe acute respiratory syndrome coronavirus 2 in controlling the corona virus disease 2019 epidemic,http://dx.doi.org/10.12998/wjcc.v8.i4.652,PMC7052559,32149049,CC BY-NC,"The current corona virus disease 2019 outbreak caused by severe acute respiratory syndrome coronavirus 2 started in Wuhan, China in December 2019 and has put the world on alert. To safeguard Chinese citizens and to strengthen global health security, China has made great efforts to control the epidemic. Many in the global community have joined China to limit the epidemic. However, discrimination and prejudice driven by fear or misinformation have been flowing globally, superseding evidence and jeopardizing the anti-severe acute respiratory syndrome coronavirus 2 efforts. We analyze this phenomenon and its underlying causes and suggest practical solutions.",2020 Feb 26,"['Ren, Shi-Yan', 'Gao, Rong-Ding', 'Chen, Ye-Lin']",World J Clin Cases,,,True
715842fa536064980818ad7e31ce511272a4b6bc,PMC,The coronavirus 2019-nCoV epidemic: Is hindsight 20/20?,http://dx.doi.org/10.1016/j.eclinm.2020.100289,PMC7057189,,CC BY-NC-ND,,2020 Mar 3,"['Malta, Monica', 'Rimoin, Anne W.', 'Strathdee, Steffanie A.']",EClinicalMedicine,,,True
ffb9c96d6bf428d73c5bcbea0524288661f0f78a,PMC,The coronavirus 2019-nCoV epidemic: Is hindsight 20/20?,http://dx.doi.org/10.1016/j.eclinm.2020.100289,PMC7057189,,CC BY-NC-ND,,2020 Mar 3,"['Malta, Monica', 'Rimoin, Anne W.', 'Strathdee, Steffanie A.']",EClinicalMedicine,,,False
f1548a1bcf0d81c278b46d24408dc7e63d9ce09d,PMC,Why can't I visit? The ethics of visitation restrictions – lessons learned from SARS,http://dx.doi.org/10.1186/cc2930,PMC1065028,15469583,NO-CC CODE,"Patients want, need and expect that their relatives will be able to visit them during inpatient admissions or accompany them during ambulatory visits. The sudden outbreak of severe acute respiratory syndrome (SARS), or a similar contagious pathogen, will restrict the number of people entering the hospital. The ethical values that underlie visitor restrictions are discussed here.",2004 Aug 31,"Rogers, Sharon",Crit Care,,,True
467694c7a219031c9be1734c7ab3bc42bfa07590,PMC,Scanning the horizon: emerging hospital-wide technologies and their impact on critical care,http://dx.doi.org/10.1186/cc3046,PMC1065120,15693973,NO-CC CODE,"This commentary represents a selective survey of developments relevant to critical care. Selected themes include advances in point-of-care diagnostic testing, glucose control, novel microbiological diagnostics and infection control measures, and developments in information technology that have implications for intensive care. The latter encompasses an early example of an artificially intelligent clinical decision support mechanism, the introduction of a national health care information technology programme (UK NPfIT) and its implications, and exotic threats to patient safety due to emergent behaviour in complex information systems.",2005 Jan 13,"['Suntharalingam, Ganesh', 'Cousins, Jonathan', 'Gattas, David', 'Chapman, Martin']",Crit Care,,,True
5f04dc1178c4d83e7f673119faa173daf1d19394,PMC,"Characterization of the frameshift signal of Edr, a mammalian example of programmed −1 ribosomal frameshifting",http://dx.doi.org/10.1093/nar/gki299,PMC1065257,15767280,NO-CC CODE,"The ribosomal frameshifting signal of the mouse embryonal carcinoma differentiation regulated (Edr) gene represents the sole documented example of programmed −1 frameshifting in mammalian cellular genes [Shigemoto,K., Brennan,J., Walls,E,. Watson,C.J., Stott,D., Rigby,P.W. and Reith,A.D. (2001), Nucleic Acids Res., 29, 4079–4088]. Here, we have employed site-directed mutagenesis and RNA structure probing to characterize the Edr signal. We began by confirming the functionality and magnitude of the signal and the role of a GGGAAAC motif as the slippery sequence. Subsequently, we derived a model of the Edr stimulatory RNA and assessed its similarity to those stimulatory RNAs found at viral frameshift sites. We found that the structure is an RNA pseudoknot possessing features typical of retroviral frameshifter pseudoknots. From these experiments, we conclude that the Edr signal and by inference, the human orthologue PEG10, do not represent a novel ‘cellular class’ of programmed −1 ribosomal frameshift signal, but rather are similar to viral examples, albeit with some interesting features. The similarity to viral frameshift signals may complicate the design of antiviral therapies that target the frameshift process.",2005 Mar 14,"['Manktelow, Emily', 'Shigemoto, Kazuhiro', 'Brierley, Ian']",Nucleic Acids Res,,,True
a77badb297bf4927419481e660ea8f1806ed91b1,PMC,Torsional restraint: a new twist on frameshifting pseudoknots,http://dx.doi.org/10.1093/nar/gki329,PMC1072802,15800212,NO-CC CODE,"mRNA pseudoknots have a stimulatory function in programmed −1 ribosomal frameshifting (−1 PRF). Though we previously presented a model for how mRNA pseudoknots might activate the mechanism for −1 PRF, it did not address the question of the role that they may play in positioning the mRNA relative to the ribosome in this process [E. P. Plant, K. L. M. Jacobs, J. W. Harger, A. Meskauskas, J. L. Jacobs, J. L. Baxter, A. N. Petrov and J. D. Dinman (2003) RNA, 9, 168–174]. A separate ‘torsional restraint’ model suggests that mRNA pseudoknots act to increase the fraction of ribosomes directed to pause with the upstream heptameric slippery site positioned at the ribosome's A- and P-decoding sites [J. D. Dinman (1995) Yeast, 11, 1115–1127]. Here, experiments using a series of ‘pseudo-pseudoknots’ having different degrees of rotational freedom were used to test this model. The results of this study support the mechanistic hypothesis that −1 ribosomal frameshifting is enhanced by torsional resistance of the mRNA pseudoknot.",2005 Mar 30,"['Plant, Ewan P.', 'Dinman, Jonathan D.']",Nucleic Acids Res,,,True
93c6eef32a1a511ee989a259eab0e12174dc6859,PMC,Correcting errors in synthetic DNA through consensus shuffling,http://dx.doi.org/10.1093/nar/gni053,PMC1072806,15800206,NO-CC CODE,"Although efficient methods exist to assemble synthetic oligonucleotides into genes and genomes, these suffer from the presence of 1–3 random errors/kb of DNA. Here, we introduce a new method termed consensus shuffling and demonstrate its use to significantly reduce random errors in synthetic DNA. In this method, errors are revealed as mismatches by re-hybridization of the population. The DNA is fragmented, and mismatched fragments are removed upon binding to an immobilized mismatch binding protein (MutS). PCR assembly of the remaining fragments yields a new population of full-length sequences enriched for the consensus sequence of the input population. We show that two iterations of consensus shuffling improved a population of synthetic green fluorescent protein (GFPuv) clones from ∼60 to >90% fluorescent, and decreased errors 3.5- to 4.3-fold to final values of ∼1 error per 3500 bp. In addition, two iterations of consensus shuffling corrected a population of GFPuv clones where all members were non-functional, to a population where 82% of clones were fluorescent. Consensus shuffling should facilitate the rapid and accurate synthesis of long DNA sequences.",2005 Mar 30,"['Binkowski, Brock F.', 'Richmond, Kathryn E.', 'Kaysen, James', 'Sussman, Michael R.', 'Belshaw, Peter J.']",Nucleic Acids Res,,,True
4185d64883b5f5a49c9032005bd17bebe47b7f90,PMC,Correcting errors in synthetic DNA through consensus shuffling,http://dx.doi.org/10.1093/nar/gni053,PMC1072806,15800206,NO-CC CODE,"Although efficient methods exist to assemble synthetic oligonucleotides into genes and genomes, these suffer from the presence of 1–3 random errors/kb of DNA. Here, we introduce a new method termed consensus shuffling and demonstrate its use to significantly reduce random errors in synthetic DNA. In this method, errors are revealed as mismatches by re-hybridization of the population. The DNA is fragmented, and mismatched fragments are removed upon binding to an immobilized mismatch binding protein (MutS). PCR assembly of the remaining fragments yields a new population of full-length sequences enriched for the consensus sequence of the input population. We show that two iterations of consensus shuffling improved a population of synthetic green fluorescent protein (GFPuv) clones from ∼60 to >90% fluorescent, and decreased errors 3.5- to 4.3-fold to final values of ∼1 error per 3500 bp. In addition, two iterations of consensus shuffling corrected a population of GFPuv clones where all members were non-functional, to a population where 82% of clones were fluorescent. Consensus shuffling should facilitate the rapid and accurate synthesis of long DNA sequences.",2005 Mar 30,"['Binkowski, Brock F.', 'Richmond, Kathryn E.', 'Kaysen, James', 'Sussman, Michael R.', 'Belshaw, Peter J.']",Nucleic Acids Res,,,False
1b118d5c8f6b4408ae66ce657f1edd5b1e6c3204,PMC,Correcting errors in synthetic DNA through consensus shuffling,http://dx.doi.org/10.1093/nar/gni053,PMC1072806,15800206,NO-CC CODE,"Although efficient methods exist to assemble synthetic oligonucleotides into genes and genomes, these suffer from the presence of 1–3 random errors/kb of DNA. Here, we introduce a new method termed consensus shuffling and demonstrate its use to significantly reduce random errors in synthetic DNA. In this method, errors are revealed as mismatches by re-hybridization of the population. The DNA is fragmented, and mismatched fragments are removed upon binding to an immobilized mismatch binding protein (MutS). PCR assembly of the remaining fragments yields a new population of full-length sequences enriched for the consensus sequence of the input population. We show that two iterations of consensus shuffling improved a population of synthetic green fluorescent protein (GFPuv) clones from ∼60 to >90% fluorescent, and decreased errors 3.5- to 4.3-fold to final values of ∼1 error per 3500 bp. In addition, two iterations of consensus shuffling corrected a population of GFPuv clones where all members were non-functional, to a population where 82% of clones were fluorescent. Consensus shuffling should facilitate the rapid and accurate synthesis of long DNA sequences.",2005 Mar 30,"['Binkowski, Brock F.', 'Richmond, Kathryn E.', 'Kaysen, James', 'Sussman, Michael R.', 'Belshaw, Peter J.']",Nucleic Acids Res,,,False
1e9f356a360887ad996c4a9ca420699d2eacf214,PMC,Correcting errors in synthetic DNA through consensus shuffling,http://dx.doi.org/10.1093/nar/gni053,PMC1072806,15800206,NO-CC CODE,"Although efficient methods exist to assemble synthetic oligonucleotides into genes and genomes, these suffer from the presence of 1–3 random errors/kb of DNA. Here, we introduce a new method termed consensus shuffling and demonstrate its use to significantly reduce random errors in synthetic DNA. In this method, errors are revealed as mismatches by re-hybridization of the population. The DNA is fragmented, and mismatched fragments are removed upon binding to an immobilized mismatch binding protein (MutS). PCR assembly of the remaining fragments yields a new population of full-length sequences enriched for the consensus sequence of the input population. We show that two iterations of consensus shuffling improved a population of synthetic green fluorescent protein (GFPuv) clones from ∼60 to >90% fluorescent, and decreased errors 3.5- to 4.3-fold to final values of ∼1 error per 3500 bp. In addition, two iterations of consensus shuffling corrected a population of GFPuv clones where all members were non-functional, to a population where 82% of clones were fluorescent. Consensus shuffling should facilitate the rapid and accurate synthesis of long DNA sequences.",2005 Mar 30,"['Binkowski, Brock F.', 'Richmond, Kathryn E.', 'Kaysen, James', 'Sussman, Michael R.', 'Belshaw, Peter J.']",Nucleic Acids Res,,,False
b3e41e68ed1d5a4a3aa74456552605e5192a70eb,PMC,Correcting errors in synthetic DNA through consensus shuffling,http://dx.doi.org/10.1093/nar/gni053,PMC1072806,15800206,NO-CC CODE,"Although efficient methods exist to assemble synthetic oligonucleotides into genes and genomes, these suffer from the presence of 1–3 random errors/kb of DNA. Here, we introduce a new method termed consensus shuffling and demonstrate its use to significantly reduce random errors in synthetic DNA. In this method, errors are revealed as mismatches by re-hybridization of the population. The DNA is fragmented, and mismatched fragments are removed upon binding to an immobilized mismatch binding protein (MutS). PCR assembly of the remaining fragments yields a new population of full-length sequences enriched for the consensus sequence of the input population. We show that two iterations of consensus shuffling improved a population of synthetic green fluorescent protein (GFPuv) clones from ∼60 to >90% fluorescent, and decreased errors 3.5- to 4.3-fold to final values of ∼1 error per 3500 bp. In addition, two iterations of consensus shuffling corrected a population of GFPuv clones where all members were non-functional, to a population where 82% of clones were fluorescent. Consensus shuffling should facilitate the rapid and accurate synthesis of long DNA sequences.",2005 Mar 30,"['Binkowski, Brock F.', 'Richmond, Kathryn E.', 'Kaysen, James', 'Sussman, Michael R.', 'Belshaw, Peter J.']",Nucleic Acids Res,,,False
184aded923f0ac3cbdbcf74d2a5b42cda0f414c2,PMC,Towards standardization of RNA quality assessment using user-independent classifiers of microcapillary electrophoresis traces,http://dx.doi.org/10.1093/nar/gni054,PMC1072807,15800207,NO-CC CODE,"While it is universally accepted that intact RNA constitutes the best representation of the steady-state of transcription, there is no gold standard to define RNA quality prior to gene expression analysis. In this report, we evaluated the reliability of conventional methods for RNA quality assessment including UV spectroscopy and 28S:18S area ratios, and demonstrated their inconsistency. We then used two new freely available classifiers, the Degradometer and RIN systems, to produce user-independent RNA quality metrics, based on analysis of microcapillary electrophoresis traces. Both provided highly informative and valuable data and the results were found highly correlated, while the RIN system gave more reliable data. The relevance of the RNA quality metrics for assessment of gene expression differences was tested by Q-PCR, revealing a significant decline of the relative expression of genes in RNA samples of disparate quality, while samples of similar, even poor integrity were found highly comparable. We discuss the consequences of these observations to minimize artifactual detection of false positive and negative differential expression due to RNA integrity differences, and propose a scheme for the development of a standard operational procedure, with optional registration of RNA integrity metrics in public repositories of gene expression data.",2005 Mar 30,"['Imbeaud, Sandrine', 'Graudens, Esther', 'Boulanger, Virginie', 'Barlet, Xavier', 'Zaborski, Patrick', 'Eveno, Eric', 'Mueller, Odilo', 'Schroeder, Andreas', 'Auffray, Charles']",Nucleic Acids Res,,,True
c3942c841518e9b2e2097dea7ee813e968000303,PMC,Management of Critically Ill Patients with Severe Acute Respiratory Syndrome (SARS),,PMC1074505,15912185,NO-CC CODE,"Severe acute respiratory syndrome (SARS) is frequently complicated with acute respiratory failure. In this article, we aim to focus on the management of the subgroup of SARS patients who are critically ill. Most SARS patients would require high flow oxygen supplementation, 20–30% required intensive care unit (ICU) or high dependency care, and 13–26% developed acute respiratory distress syndrome (ARDS). In some of these patients, the clinical course can progress relentlessly to septic shock and/or multiple organ dysfunction syndrome (MODS). The management of critically ill SARS patients requires timely institution of pharmacotherapy where applicable and supportive treatment (oxygen therapy, noninvasive and invasive ventilation). Superimposed bacterial and other opportunistic infections are common, especially in those treated with mechanical ventilation. Subcutaneous emphysema, pneumothoraces and pneumomediastinum may arise spontaneously or as a result of positive ventilatory assistance. Older age is a consistently a poor prognostic factor. Appropriate use of personal protection equipment and adherence to infection control measures is mandatory for effective infection control. Much of the knowledge about the clinical aspects of SARS is based on retrospective observational data and randomized-controlled trials are required for confirmation. Physicians and scientists all over the world should collaborate to study this condition which may potentially threaten human existence.",2004 Mar 10,"['LAU, Arthur Chun-Wing', 'YAM, Loretta Yin-Chun', 'SO, Loletta Kit-Ying']",Int J Med Sci,,,True
5ae641a5bf24b53a895f5f2f04254cc00e909c08,PMC,Species-independent detection of RNA virus by representational difference analysis using non-ribosomal hexanucleotides for reverse transcription,http://dx.doi.org/10.1093/nar/gni064,PMC1074749,15817564,NO-CC CODE,"A method for the isolation of genomic fragments of RNA virus based on cDNA representational difference analysis (cDNA RDA) was developed. cDNA RDA has been applied for the subtraction of poly(A)(+) RNAs but not for poly(A)(−) RNAs, such as RNA virus genomes, owing to the vast quantity of ribosomal RNAs. We constructed primers for inefficient reverse transcription of ribosomal sequences based on the distribution analysis of hexanucleotide patterns in ribosomal RNA. The analysis revealed that distributions of hexanucleotide patterns in ribosomal RNA and virus genome were different. We constructed 96 hexanucleotides (non-ribosomal hexanucleotides) and used them as mixed primers for reverse transcription of cDNA RDA. A synchronous analysis of hexanucleotide patterns in known viral sequences showed that all the known genomic-size viral sequences include non-ribosomal hexanucleotides. In a model experiment, when non-ribosomal hexanucleotides were used as primers, in vitro transcribed plasmid RNA was efficiently reverse transcribed when compared with ribosomal RNA of rat cells. Using non-ribosomal primers, the cDNA fragments of severe acute respiratory syndrome coronavirus and bovine parainfluenza virus 3 were efficiently amplified by subtracting the cDNA amplicons derived from uninfected cells from those that were derived from virus-infected cells. The results suggest that cDNA RDA with non-ribosomal primers can be used for species-independent detection of viruses, including new viruses.",2005 Apr 7,"['Endoh, Daiji', 'Mizutani, Tetsuya', 'Kirisawa, Rikio', 'Maki, Yoshiyuki', 'Saito, Hidetoshi', 'Kon, Yasuhiro', 'Morikawa, Shigeru', 'Hayashi, Masanobu']",Nucleic Acids Res,,,True
40e41f0c52b39669dee24e37875d7a9fabc38636,PMC,Factors affecting translation at the programmed −1 ribosomal frameshifting site of Cocksfoot mottle virus RNA in vivo,http://dx.doi.org/10.1093/nar/gki521,PMC1083427,15843686,NO-CC CODE,"The ratio between proteins P27 and replicase of Cocksfoot mottle virus (CfMV) is regulated via a −1 programmed ribosomal frameshift (−1 PRF). A minimal frameshift signal with a slippery U UUA AAC heptamer and a downstream stem–loop structure was inserted into a dual reporter vector and directed −1 PRF with an efficiency of 14.4 ± 1.9% in yeast and 2.4 ± 0.7% in bacteria. P27-encoding CfMV sequence flanking the minimal frameshift signal caused ∼2-fold increase in the −1 PRF efficiencies both in yeast and in bacteria. In addition to the expected fusion proteins, termination products ending putatively at the frameshift site were found in yeast cells. We propose that the amount of premature translation termination from control mRNAs played a role in determining the calculated −1PRF efficiency. Co-expression of CfMV P27 with the dual reporter vector containing the minimal frameshift signal reduced the production of the downstream reporter, whereas replicase co-expression had no pronounced effect. This finding allows us to propose that CfMV protein P27 may influence translation at the frameshift site but the mechanism needs to be elucidated.",2005 Apr 20,"['Mäkeläinen, Katri', 'Mäkinen, Kristiina']",Nucleic Acids Res,,,True
7000185289991946d912ac5f4b9451cce4d228a2,PMC,"Inhibition of SARS-CoV 3C-like Protease Activity by Theaflavin-3,3′-digallate (TF3)",http://dx.doi.org/10.1093/ecam/neh081,PMC1142193,15937562,NO-CC CODE,"SARS-CoV is the causative agent of severe acute respiratory syndrome (SARS). The virally encoded 3C-like protease (3CL(Pro)) has been presumed critical for the viral replication of SARS-CoV in infected host cells. In this study, we screened a natural product library consisting of 720 compounds for inhibitory activity against 3CL(Pro). Two compounds in the library were found to be inhibitive: tannic acid (IC(50) = 3 µM) and 3-isotheaflavin-3-gallate (TF2B) (IC(50) = 7 µM). These two compounds belong to a group of natural polyphenols found in tea. We further investigated the 3CL(Pro)-inhibitory activity of extracts from several different types of teas, including green tea, oolong tea, Puer tea and black tea. Our results indicated that extracts from Puer and black tea were more potent than that from green or oolong teas in their inhibitory activities against 3CL(Pro). Several other known compositions in teas were also evaluated for their activities in inhibiting 3CL(Pro). We found that caffeine, (—)-epigallocatechin gallte (EGCg), epicatechin (EC), theophylline (TP), catechin (C), epicatechin gallate (ECg) and epigallocatechin (EGC) did not inhibit 3CL(Pro) activity. Only theaflavin-3,3′-digallate (TF3) was found to be a 3CL(Pro) inhibitor. This study has resulted in the identification of new compounds that are effective 3CL(Pro) inhibitors.",2005 Jun 7,"['Chen, Chia-Nan', 'Lin, Coney P. C.', 'Huang, Kuo-Kuei', 'Chen, Wei-Cheng', 'Hsieh, Hsin-Pang', 'Liang, Po-Huang', 'Hsu, John T.-A.']",Evid Based Complement Alternat Med,,,True
47e5a99b14df794d9c33c1b1e8ff258d3f89a1d2,PMC,"PRED(BALB/c): a system for the prediction of peptide binding to H2(d) molecules, a haplotype of the BALB/c mouse",http://dx.doi.org/10.1093/nar/gki479,PMC1160239,15980450,NO-CC CODE,"PRED(BALB/c) is a computational system that predicts peptides binding to the major histocompatibility complex-2 (H2(d)) of the BALB/c mouse, an important laboratory model organism. The predictions include the complete set of H2(d) class I (H2-K(d), H2-L(d) and H2-D(d)) and class II (I-E(d) and I-A(d)) molecules. The prediction system utilizes quantitative matrices, which were rigorously validated using experimentally determined binders and non-binders and also by in vivo studies using viral proteins. The prediction performance of PRED(BALB/c) is of very high accuracy. To our knowledge, this is the first online server for the prediction of peptides binding to a complete set of major histocompatibility complex molecules in a model organism (H2(d) haplotype). PRED(BALB/c) is available at .",2005 Jul 1,"['Zhang, Guang Lan', 'Srinivasan, Kellathur N.', 'Veeramani, Anitha', 'August, J. Thomas', 'Brusic, Vladimir']",Nucleic Acids Res,,,True
96650e6fa280653c83e6f9b1ba1e5217f45e4799,PMC,GENSTYLE: exploration and analysis of DNA sequences with genomic signature,http://dx.doi.org/10.1093/nar/gki489,PMC1160249,15980524,NO-CC CODE,"GENSTYLE () is a workspace designed for the characterization and classification of nucleotide sequences. Based on the genomic signature paradigm, GENSTYLE focuses on oligonucleotide frequencies in DNA sequences. Users can select sequences of interest in the GENSTYLE companion database, where the whole set of GenBank sequences is grouped per species, or upload their own sequences to work with. Tools for the exploration and analysis of signatures allow (i) identification of the origin of DNA segments (detection of rare species or species for which technical problems prevent fast characterization, such as micro-organisms with slow growth), (ii) analysis of the homogeneity of a genome and isolation of areas with novel functionality (horizontal transfers for example) – and (iii) molecular phylogeny and taxonomy.",2005 Jul 1,"['Fertil, Bernard', 'Massin, Matthieu', 'Lespinats, Sylvain', 'Devic, Caroline', 'Dumee, Philippe', 'Giron, Alain']",Nucleic Acids Res,,,True
6eeaffdb22b4e310867262d1891a1442769c7803,PMC,A universal BMV-based RNA recombination system—how to search for general rules in RNA recombination,http://dx.doi.org/10.1093/nar/gni106,PMC1174899,16002784,NO-CC CODE,"At present, there is no doubt that RNA recombination is one of the major factors responsible for the generation of new RNA viruses and retroviruses. Numerous experimental systems have been created to investigate this complex phenomenon. Consequently, specific RNA structural motifs mediating recombination have been identified in several viruses. Unfortunately, up till now a unified model of genetic RNA recombination has not been formulated, mainly due to difficulties with the direct comparison of data obtained for different RNA-based viruses. To solve this problem, we have attempted to construct a universal system in which the recombination activity of various RNA sequences could be tested. To this end, we have used brome mosaic virus, a model (+)RNA virus of plants, for which the structural requirements of RNA recombination are well defined. The effectiveness of the new homomolecular system has been proven in an experiment involving two RNA sequences derived from the hepatitis C virus genome. In addition, comparison of the data obtained with the homomolecular system with those generated earlier using the heteromolecular one has provided new evidence that the mechanisms of homologous and non-homologous recombination are different and depend on the virus' mode of replication.",2005 Jul 7,"['Alejska, Magdalena', 'Figlerowicz, Magdalena', 'Malinowska, Nelli', 'Urbanowicz, Anna', 'Figlerowicz, Marek']",Nucleic Acids Res,,,True
c35675e5426c3a70835a0ce56c2921b4416f8686,PMC,Engendering enthusiasm for sustainable disaster critical care response: why this is of consequence to critical care professionals?,http://dx.doi.org/10.1186/cc3048,PMC1175928,15774058,NO-CC CODE,"Disaster medical response has historically focused on the pre-hospital and initial treatment needs of casualties. In particular, the critical care component of many disaster response plans is incomplete. Equally important, routinely available critical care resources are almost always insufficient to respond to disasters that generate anything beyond a 'modest' casualty stream. Large-scale monetary funding to effectively remedy these shortfalls is unavailable. Education, training, and improved planning are our most effective initial steps. We suggest several areas for further development, including dual usage of resources that may specifically augment critical care disaster medical capabilities over time.",2005 Jan 27,"['Dara, Saqib I', 'Ashton, Rendell W', 'Farmer, J Christopher']",Crit Care,,,True
363d8e5ae1bb4bc246692ca6ef794b559b046b54,PMC,Biochip sensors for the rapid and sensitive detection of viral disease,http://dx.doi.org/10.1186/gb-2005-6-6-112,PMC1175961,15960809,NO-CC CODE,Recent advances in DNA and protein microarray methodology and the emerging technology of cell-based sensors have massively increased the speed and sensitivity with which we can detect viral infections. The advantages of the multi-parameter microarray technologies could be combined with the speed and sensitivity of cell-based systems to give 'cell-omic' sensors.,2005 May 26,"['Livingston, Andrew D', 'Campbell, Colin J', 'Wagner, Edward K', 'Ghazal, Peter']",Genome Biol,,,True
308a157fe5e9a630ded41e9d708dd50df3b6149b,PMC,An atypical RNA pseudoknot stimulator and an upstream attenuation signal for −1 ribosomal frameshifting of SARS coronavirus,http://dx.doi.org/10.1093/nar/gki731,PMC1182165,16055920,NO-CC CODE,"The −1 ribosomal frameshifting requires the existence of an in cis RNA slippery sequence and is promoted by a downstream stimulator RNA. An atypical RNA pseudoknot with an extra stem formed by complementary sequences within loop 2 of an H-type pseudoknot is characterized in the severe acute respiratory syndrome coronavirus (SARS CoV) genome. This pseudoknot can serve as an efficient stimulator for −1 frameshifting in vitro. Mutational analysis of the extra stem suggests frameshift efficiency can be modulated via manipulation of the secondary structure within the loop 2 of an infectious bronchitis virus-type pseudoknot. More importantly, an upstream RNA sequence separated by a linker 5′ to the slippery site is also identified to be capable of modulating the −1 frameshift efficiency. RNA sequence containing this attenuation element can downregulate −1 frameshifting promoted by an atypical pseudoknot of SARS CoV and two other pseudoknot stimulators. Furthermore, frameshift efficiency can be reduced to half in the presence of the attenuation signal in vivo. Therefore, this in cis RNA attenuator represents a novel negative determinant of general importance for the regulation of −1 frameshift efficiency, and is thus a potential antiviral target.",2005 Jul 29,"['Su, Mei-Chi', 'Chang, Chung-Te', 'Chu, Chiu-Hui', 'Tsai, Ching-Hsiu', 'Chang, Kung-Yao']",Nucleic Acids Res,,,True
cc698ffabf545da2fd7ee6a5cb4f25d9102a856a,PMC,eCAM benefits from diversity that derives from CAM,http://dx.doi.org/10.1093/ecam/neh120,PMC1193560,16136204,NO-CC CODE,,2005 Sep,"Cooper, Edwin L.",Evid Based Complement Alternat Med,,,True
95aec306660c1b7519e9f019d92cc3a8206481e4,PMC,The influence of locked nucleic acid residues on the thermodynamic properties of 2′-O-methyl RNA/RNA heteroduplexes,http://dx.doi.org/10.1093/nar/gki789,PMC1201327,16155181,NO-CC CODE,"The influence of locked nucleic acid (LNA) residues on the thermodynamic properties of 2′-O-methyl RNA/RNA heteroduplexes is reported. Optical melting studies indicate that LNA incorporated into an otherwise 2′-O-methyl RNA oligonucleotide usually, but not always, enhances the stabilities of complementary duplexes formed with RNA. Several trends are apparent, including: (i) a 3′ terminal U LNA and 5′ terminal LNAs are less stabilizing than interior and other 3′ terminal LNAs; (ii) most of the stability enhancement is achieved when LNA nucleotides are separated by at least one 2′-O-methyl nucleotide; and (iii) the effects of LNA substitutions are approximately additive when the LNA nucleotides are separated by at least one 2′-O-methyl nucleotide. An equation is proposed to approximate the stabilities of complementary duplexes formed with RNA when at least one 2′-O-methyl nucleotide separates LNA nucleotides. The sequence dependence of 2′-O-methyl RNA/RNA duplexes appears to be similar to that of RNA/RNA duplexes, and preliminary nearest-neighbor free energy increments at 37°C are presented for 2′-O-methyl RNA/RNA duplexes. Internal mismatches with LNA nucleotides significantly destabilize duplexes with RNA.",2005 Sep 9,"['Kierzek, Elzbieta', 'Ciesielska, Anna', 'Pasternak, Karol', 'Mathews, David H.', 'Turner, Douglas H.', 'Kierzek, Ryszard']",Nucleic Acids Res,,,True
8ce5bc85657209e5380bfdae424fd9bc2816e31d,PMC,The influence of locked nucleic acid residues on the thermodynamic properties of 2′-O-methyl RNA/RNA heteroduplexes,http://dx.doi.org/10.1093/nar/gki789,PMC1201327,16155181,NO-CC CODE,"The influence of locked nucleic acid (LNA) residues on the thermodynamic properties of 2′-O-methyl RNA/RNA heteroduplexes is reported. Optical melting studies indicate that LNA incorporated into an otherwise 2′-O-methyl RNA oligonucleotide usually, but not always, enhances the stabilities of complementary duplexes formed with RNA. Several trends are apparent, including: (i) a 3′ terminal U LNA and 5′ terminal LNAs are less stabilizing than interior and other 3′ terminal LNAs; (ii) most of the stability enhancement is achieved when LNA nucleotides are separated by at least one 2′-O-methyl nucleotide; and (iii) the effects of LNA substitutions are approximately additive when the LNA nucleotides are separated by at least one 2′-O-methyl nucleotide. An equation is proposed to approximate the stabilities of complementary duplexes formed with RNA when at least one 2′-O-methyl nucleotide separates LNA nucleotides. The sequence dependence of 2′-O-methyl RNA/RNA duplexes appears to be similar to that of RNA/RNA duplexes, and preliminary nearest-neighbor free energy increments at 37°C are presented for 2′-O-methyl RNA/RNA duplexes. Internal mismatches with LNA nucleotides significantly destabilize duplexes with RNA.",2005 Sep 9,"['Kierzek, Elzbieta', 'Ciesielska, Anna', 'Pasternak, Karol', 'Mathews, David H.', 'Turner, Douglas H.', 'Kierzek, Ryszard']",Nucleic Acids Res,,,False
d1e1e8dba793fcab2ab717c2b9e34009768a699c,PMC,The capacity to change: building global environmental health expertise.,,PMC1241591,12842794,NO-CC CODE,,2003 Jul,"Karasov, Corliss",Environ Health Perspect,,,True
a83597bafe4870a3b5bf41a3012cb7c94d79a7ff,PMC,Emerging diseases threaten conservation.,,PMC1241623,12896863,NO-CC CODE,,2003 Aug,"['Epstein, Paul R', 'Chivian, Eric', 'Frith, Kathleen']",Environ Health Perspect,,,True
bf417a4d999dae8d6ad38e62fc69f2a578c58f16,PMC,Conservation medicine: combining the best of all worlds.,,PMC1241627,12896870,NO-CC CODE,,2003 Aug,"Weinhold, Bob",Environ Health Perspect,,,True
d7eab0c035d397fbe68ae0506f2d9f474a34e3c4,PMC,Infectious disease: the human costs of our environmental errors.,,PMC1241811,14698949,NO-CC CODE,,2004 Jan,"Weinhold, Bob",Environ Health Perspect,,,False
8f4ec7b6c58e8cafcc1f8eb3380370621110202b,PMC,Unhealthy Landscapes: Policy Recommendations on Land Use Change and Infectious Disease Emergence,http://dx.doi.org/10.1289/ehp.6877,PMC1247383,15238283,NO-CC CODE,"Anthropogenic land use changes drive a range of infectious disease outbreaks and emergence events and modify the transmission of endemic infections. These drivers include agricultural encroachment, deforestation, road construction, dam building, irrigation, wetland modification, mining, the concentration or expansion of urban environments, coastal zone degradation, and other activities. These changes in turn cause a cascade of factors that exacerbate infectious disease emergence, such as forest fragmentation, disease introduction, pollution, poverty, and human migration. The Working Group on Land Use Change and Disease Emergence grew out of a special colloquium that convened international experts in infectious diseases, ecology, and environmental health to assess the current state of knowledge and to develop recommendations for addressing these environmental health challenges. The group established a systems model approach and priority lists of infectious diseases affected by ecologic degradation. Policy-relevant levels of the model include specific health risk factors, landscape or habitat change, and institutional (economic and behavioral) levels. The group recommended creating Centers of Excellence in Ecology and Health Research and Training, based at regional universities and/or research institutes with close links to the surrounding communities. The centers’ objectives would be 3-fold: a) to provide information to local communities about the links between environmental change and public health; b) to facilitate fully interdisciplinary research from a variety of natural, social, and health sciences and train professionals who can conduct interdisciplinary research; and c) to engage in science-based communication and assessment for policy making toward sustainable health and ecosystems.",2004 Jul 22,"['Patz, Jonathan A.', 'Daszak, Peter', 'Tabor, Gary M.', 'Aguirre, A. Alonso', 'Pearl, Mary', 'Epstein, Jon', 'Wolfe, Nathan D.', 'Kilpatrick, A. Marm', 'Foufopoulos, Johannes', 'Molyneux, David', 'Bradley, David J.', None]",Environ Health Perspect,,,True
d450fc8885843d48772df9a898552302f8c80b98,PMC,Draft versus finished sequence data for DNA and protein diagnostic signature development,http://dx.doi.org/10.1093/nar/gki896,PMC1266063,16243783,NO-CC CODE,"Sequencing pathogen genomes is costly, demanding careful allocation of limited sequencing resources. We built a computational Sequencing Analysis Pipeline (SAP) to guide decisions regarding the amount of genomic sequencing necessary to develop high-quality diagnostic DNA and protein signatures. SAP uses simulations to estimate the number of target genomes and close phylogenetic relatives (near neighbors or NNs) to sequence. We use SAP to assess whether draft data are sufficient or finished sequencing is required using Marburg and variola virus sequences. Simulations indicate that intermediate to high-quality draft with error rates of 10(−3)–10(−5) (∼8× coverage) of target organisms is suitable for DNA signature prediction. Low-quality draft with error rates of ∼1% (3× to 6× coverage) of target isolates is inadequate for DNA signature prediction, although low-quality draft of NNs is sufficient, as long as the target genomes are of high quality. For protein signature prediction, sequencing errors in target genomes substantially reduce the detection of amino acid sequence conservation, even if the draft is of high quality. In summary, high-quality draft of target and low-quality draft of NNs appears to be a cost-effective investment for DNA signature prediction, but may lead to underestimation of predicted protein signatures.",2005 Oct 20,"['Gardner, Shea N.', 'Lam, Marisa W.', 'Smith, Jason R.', 'Torres, Clinton L.', 'Slezak, Tom R.']",Nucleic Acids Res,,,True
46eed3a4ec7612d74e9295fe57c982755948feae,PMC,Clinical review: SARS – lessons in disaster management,http://dx.doi.org/10.1186/cc3041,PMC1269424,16137388,NO-CC CODE,"Disaster management plans have traditionally been required to manage major traumatic events that create a large number of victims. Infectious diseases, whether they be natural (e.g. SARS [severe acute respiratory syndrome] and influenza) or the result of bioterrorism, have the potential to create a large influx of critically ill into our already strained hospital systems. With proper planning, hospitals, health care workers and our health care systems can be better prepared to deal with such an eventuality. This review explores the Toronto critical care experience of coping in the SARS outbreak disaster. Our health care system and, in particular, our critical care system were unprepared for this event, and as a result the impact that SARS had was worse than it could have been. Nonetheless, we were able to organize a response rapidly during the outbreak. By describing our successes and failures, we hope to help others to learn and avoid the problems we encountered as they develop their own disaster management plans in anticipation of similar future situations.",2005 Jan 13,"['Hawryluck, Laura', 'Lapinsky, Stephen E', 'Stewart, Thomas E']",Crit Care,,,True
f7778201dec1d1cf942577562819fa9841b1db50,PMC,Bench-to-bedside review: Outcome predictions for critically ill patients in the emergency department,http://dx.doi.org/10.1186/cc3518,PMC1269432,16137387,NO-CC CODE,"The escalating number of emergency department (ED) visits, length of stay, and hospital overcrowding have been associated with an increasing number of critically ill patients cared for in the ED. Existing physiologic scoring systems have traditionally been used for outcome prediction, clinical research, quality of care analysis, and benchmarking in the intensive care unit (ICU) environment. However, there is limited experience with scoring systems in the ED, while early and aggressive intervention in critically ill patients in the ED is becoming increasingly important. Development and implementation of physiologic scoring systems specific to this setting is potentially useful in the early recognition and prognostication of illness severity. A few existing ICU physiologic scoring systems have been applied in the ED, with some success. Other ED specific scoring systems have been developed for various applications: recognition of patients at risk for infection; prediction of mortality after critical care transport; prediction of in-hospital mortality after admission; assessment of prehospital therapeutic efficacy; screening for severe acute respiratory syndrome; and prediction of pediatric hospital admission. Further efforts at developing unique physiologic assessment methodologies for use in the ED will improve quality of patient care, aid in resource allocation, improve prognostic accuracy, and objectively measure the impact of early intervention in the ED.",2005 Apr 18,"['Hargrove, Jenny', 'Nguyen, H Bryant']",Crit Care,,,True
a04f95dd2586d12bce1fab7cf5208046923da10a,PMC,Critical care during epidemics,http://dx.doi.org/10.1186/cc3533,PMC1269436,16137366,NO-CC CODE,"We recommend several actions that could improve hospitals' abilities to deliver critical care during epidemics involving large numbers of victims. In the absence of careful pre-event planning, demand for critical care services may quickly exceed available intensive care unit (ICU) staff, beds and equipment, leaving the bulk of the infected populace without benefit of potentially lifesaving critical care. The toll of death may be inversely proportional to the ability to augment critical care capacity, so critical care health care professionals must take the lead for planning and preparing to care for numbers of seriously ill patients that far exceed available ICU beds.",2005 Apr 27,"['Rubinson, Lewis', ""O'Toole, Tara""]",Crit Care,,,True
7d53d33c7dc9188bb757f20b10714041aa84f59e,PMC,An analysis of the feasibility of short read sequencing,http://dx.doi.org/10.1093/nar/gni170,PMC1278949,16275781,NO-CC CODE,"Several methods for ultra high-throughput DNA sequencing are currently under investigation. Many of these methods yield very short blocks of sequence information (reads). Here we report on an analysis showing the level of genome sequencing possible as a function of read length. It is shown that re-sequencing and de novo sequencing of the majority of a bacterial genome is possible with read lengths of 20–30 nt, and that reads of 50 nt can provide reconstructed contigs (a contiguous fragment of sequence data) of 1000 nt and greater that cover 80% of human chromosome 1.",2005 Nov 7,"['Whiteford, Nava', 'Haslam, Niall', 'Weber, Gerald', 'Prügel-Bennett, Adam', 'Essex, Jonathan W.', 'Roach, Peter L.', 'Bradley, Mark', 'Neylon, Cameron']",Nucleic Acids Res,,,True
e2619c76a8dde67ace5623870a263a365d2c944b,PMC,Bench-to-bedside review: Adjuncts to mechanical ventilation in patients with acute lung injury,http://dx.doi.org/10.1186/cc3763,PMC1297606,16277735,NO-CC CODE,"Mechanical ventilation is indispensable for the survival of patients with acute lung injury and acute respiratory distress syndrome. However, excessive tidal volumes and inadequate lung recruitment may contribute to mortality by causing ventilator-induced lung injury. This bench-to-bedside review presents the scientific rationale for using adjuncts to mechanical ventilation aimed at optimizing lung recruitment and preventing the deleterious consequences of reduced tidal volume. To enhance CO(2 )elimination when tidal volume is reduced, the following are possible: first, ventilator respiratory frequency can be increased without necessarily generating intrinsic positive end-expiratory pressure; second, instrumental dead space can be reduced by replacing the heat and moisture exchanger with a conventional humidifier; and third, expiratory washout can be used for replacing the CO(2)-laden gas present at end expiration in the instrumental dead space by a fresh gas (this method is still experimental). For optimizing lung recruitment and preventing lung derecruitment there are the following possibilities: first, recruitment manoeuvres may be performed in the most hypoxaemic patients before implementing the preset positive end-expiratory pressure or after episodes of accidental lung derecruitment; second, the patient can be turned to the prone position; third, closed-circuit endotracheal suctioning is to be preferred to open endotracheal suctioning.",2005 Jun 28,"['Rouby, Jean-Jacques', 'Lu, Qin']",Crit Care,,,True
5722e1b167fe879fc2901ba8ea2fa69fec89a6f7,PMC,Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers,http://dx.doi.org/10.1371/journal.ppat.0020001,PMC1326218,16415982,NO-CC CODE,"The filoviruses Marburg virus and Ebola virus (EBOV) quickly outpace host immune responses and cause hemorrhagic fever, resulting in case fatality rates as high as 90% in humans and nearly 100% in nonhuman primates. The development of an effective therapeutic for EBOV is a daunting public health challenge and is hampered by a paucity of knowledge regarding filovirus pathogenesis. This report describes a successful strategy for interfering with EBOV infection using antisense phosphorodiamidate morpholino oligomers (PMOs). A combination of EBOV-specific PMOs targeting sequences of viral mRNAs for the viral proteins (VPs) VP24, VP35, and RNA polymerase L protected rodents in both pre- and post-exposure therapeutic regimens. In a prophylactic proof-of-principal trial, the PMOs also protected 75% of rhesus macaques from lethal EBOV infection. The work described here may contribute to development of designer, “druggable” countermeasures for filoviruses and other microbial pathogens.",2006 Jan 13,"['Warfield, Kelly L', 'Swenson, Dana L', 'Olinger, Gene G', 'Nichols, Donald K', 'Pratt, William D', 'Blouch, Robert', 'Stein, David A', 'Aman, M. Javad', 'Iversen, Patrick L', 'Bavari, Sina']",PLoS Pathog,,,True
49f7f726a602a3e20d2525a7b696fd4a41d8430c,PMC,TaqMan probe array for quantitative detection of DNA targets,http://dx.doi.org/10.1093/nar/gnj006,PMC1326252,,NO-CC CODE,"To date real-time quantitative PCR and gene expression microarrays are the methods of choice for quantification of nucleic acids. Herein, we described a unique fluorescence resonance energy transfer-based microarray platform for real-time quantification of nucleic acid targets that combines advantages of both and reduces their limitations. A set of 3′ amino-modified TaqMan probes were designed and immobilized on a glass slide composing a regular microarray pattern, and used as probes in the consecutive PCR carried out on the surface. During the extension step of the PCR, 5′ nuclease activity of DNA polymerase will cleave quencher dyes of the immobilized probe in the presence of nucleic acids targets. The increase of fluorescence intensities generated by the change in physical distance between reporter fluorophore and quencher moiety of the probes were collected by a confocal scanner. Using this new approach we successfully monitored five different pathogenic genomic DNAs and analyzed the dynamic characteristics of fluorescence intensity changes on the TaqMan probe array. The results indicate that the TaqMan probe array on a planar glass slide monitors DNA targets with excellent specificity as well as high sensitivity. This set-up offers the great advantage of real-time quantitative detection of DNA targets in a parallel array format.",2006 Jan 10,"['Liu, Heping', 'Wang, Hong', 'Shi, Zhiyang', 'Wang, Hua', 'Yang, Chaoyong', 'Silke, Spering', 'Tan, Weihong', 'Lu, Zuhong']",Nucleic Acids Res,,,True
7c7c02af9951523fe4147d5e43f322b139cc966c,PMC,Identification of Hepta- and Octo-Uridine stretches as sole signals for programmed +1 and −1 ribosomal frameshifting during translation of SARS-CoV ORF 3a variants,http://dx.doi.org/10.1093/nar/gkl017,PMC1383626,16500894,NO-CC CODE,"Programmed frameshifting is one of the translational recoding mechanisms that read the genetic code in alternative ways. This process is generally programmed by signals at defined locations in a specific mRNA. In this study, we report the identification of hepta- and octo-uridine stretches as sole signals for programmed +1 and −1 ribosomal frameshifting during translation of severe acute respiratory syndrome coronavirus (SARS-CoV) ORF 3a variants. SARS-CoV ORF 3a encodes a minor structural protein of 274 amino acids. Over the course of cloning and expression of the gene, a mixed population of clones with six, seven, eight and nine T stretches located 14 nt downstream of the initiation codon was found. In vitro and in vivo expression of clones with six, seven and eight Ts, respectively, showed the detection of the full-length 3a protein. Mutagenesis studies led to the identification of the hepta- and octo-uridine stretches as slippery sequences for efficient frameshifting. Interestingly, no stimulatory elements were found in the sequences upstream or downstream of the slippage site. When the hepta- and octo-uridine stretches were used to replace the original slippery sequence of the SARS-CoV ORF 1a and 1b, efficient frameshift events were observed. Furthermore, the efficiencies of frameshifting mediated by the hepta- and octo-uridine stretches were not affected by mutations introduced into a downstream stem–loop structure that totally abolish the frameshift event mediated by the original slippery sequence of ORF 1a and 1b. Taken together, this study identifies the hepta- and octo-uridine stretches that function as sole elements for efficient +1 and −1 ribosomal frameshift events.",2006 Feb 25,"['Wang, Xiaoxing', 'Wong, Sek-Man', 'Liu, D. X.']",Nucleic Acids Res,,,True
1e1286db212100993d03cc22374b624f7caee956,PMC,Airborne rhinovirus detection and effect of ultraviolet irradiation on detection by a semi-nested RT-PCR assay,http://dx.doi.org/10.1186/1471-2458-3-5,PMC140314,12525263,NO-CC CODE,"BACKGROUND: Rhinovirus, the most common cause of upper respiratory tract infections, has been implicated in asthma exacerbations and possibly asthma deaths. Although the method of transmission of rhinoviruses is disputed, several studies have demonstrated that aerosol transmission is a likely method of transmission among adults. As a first step in studies of possible airborne rhinovirus transmission, we developed methods to detect aerosolized rhinovirus by extending existing technology for detecting infectious agents in nasal specimens. METHODS: We aerosolized rhinovirus in a small aerosol chamber. Experiments were conducted with decreasing concentrations of rhinovirus. To determine the effect of UV irradiation on detection of rhinoviral aerosols, we also conducted experiments in which we exposed aerosols to a UV dose of 684 mJ/m(2). Aerosols were collected on Teflon filters and rhinovirus recovered in Qiagen AVL buffer using the Qiagen QIAamp Viral RNA Kit (Qiagen Corp., Valencia, California) followed by semi-nested RT-PCR and detection by gel electrophoresis. RESULTS: We obtained positive results from filter samples that had collected at least 1.3 TCID(50 )of aerosolized rhinovirus. Ultraviolet irradiation of airborne virus at doses much greater than those used in upper-room UV germicidal irradiation applications did not inhibit subsequent detection with the RT-PCR assay. CONCLUSION: The air sampling and extraction methodology developed in this study should be applicable to the detection of rhinovirus and other airborne viruses in the indoor air of offices and schools. This method, however, cannot distinguish UV inactivated virus from infectious viral particles.",2003 Jan 13,"['Myatt, Theodore A', 'Johnston, Sebastian L', 'Rudnick, Stephen', 'Milton, Donald K']",BMC Public Health,,,True
0a6e9aa35d1320355bf071879e98aabcacfe2b85,PMC,Twelve Essentials of Science-based Policy,,PMC1435713,16164820,NO-CC CODE,"This article presents a systematic framework of 12 essentials, or basic elements, of science-based policy. The 12 essentials are grouped into three categories, or areas, as follows: 1) knowledge generation, which includes credible design, accurate data, sound analysis, and comprehensive synthesis; 2) knowledge exchange, which includes relevant content, appropriate translation, timely dissemination, and modulated release; and 3) knowledge uptake, which includes accessible information, readable message, motivated user, and rewarding outcome.",2005 Sep 15,"Choi, Bernard C.K",Prev Chronic Dis,,,True
5543303ea370910fdff1ef7e9f77ddfe136ff683,PMC,Polyadenylation of genomic RNA and initiation of antigenomic RNA in a positive-strand RNA virus are controlled by the same cis-element,http://dx.doi.org/10.1093/nar/gkl349,PMC1474053,16738134,NO-CC CODE,"Genomes and antigenomes of many positive-strand RNA viruses contain 3′-poly(A) and 5′-poly(U) tracts, respectively, serving as mutual templates. Mechanism(s) controlling the length of these homopolymeric stretches are not well understood. Here, we show that in coxsackievirus B3 (CVB3) and three other enteroviruses the poly(A) tract is ∼80–90 and the poly(U) tract is ∼20 nt-long. Mutagenesis analysis indicate that the length of the CVB3 3′-poly(A) is determined by the oriR, a cis-element in the 3′-noncoding region of viral RNA. In contrast, while mutations of the oriR inhibit initiation of (−) RNA synthesis, they do not affect the 5′-poly(U) length. Poly(A)-lacking genomes are able to acquire genetically unstable AU-rich poly(A)-terminated 3′-tails, which may be generated by a mechanism distinct from the cognate viral RNA polyadenylation. The aberrant tails ensure only inefficient replication. The possibility of RNA replication independent of oriR and poly(A) demonstrate that highly debilitated viruses are able to survive by utilizing ‘emergence’, perhaps atavistic, mechanisms.",2006 May 31,"['van Ooij, Mark J. M.', 'Polacek, Charlotta', 'Glaudemans, Dirk H. R. F.', 'Kuijpers, Judith', 'van Kuppeveld, Frank J. M.', 'Andino, Raul', 'Agol, Vadim I.', 'Melchers, Willem J. G.']",Nucleic Acids Res,,,True
c128cbe506d417582e13e50a2028a34d13c6b2fb,PMC,Abstracts of Poster Session: Abstracts,,PMC1474450,,NO-CC CODE,,1987 Nov,,Environ Health Perspect,,,True
e7f311d3c752063f75f28de85abd5f82eacab413,PMC,Epicatechins Purified from Green Tea (Camellia sinensis) Differentially Suppress Growth of Gender-Dependent Human Cancer Cell Lines,http://dx.doi.org/10.1093/ecam/nel003,PMC1475929,16786054,NO-CC CODE,"The anticancer potential of catechins derived from green tea is not well understood, in part because catechin-related growth suppression and/or apoptosis appears to vary with the type and stage of malignancy as well as with the type of catechin. This in vitro study examined the biological effects of epicatechin (EC), epigallocatechin (EGC), EC 3-gallate (ECG) and EGC 3-gallate (EGCG) in cell lines from human gender-specific cancers. Cell lines developed from organ-confined (HH870) and metastatic (DU145) prostate cancer, and from moderately (HH450) and poorly differentiated (HH639) epithelial ovarian cancer were grown with or without EC, EGC, ECG or EGCG. When untreated cells reached confluency, viability and doubling time were measured for treated and untreated cells. Whereas EC treatment reduced proliferation of HH639 cells by 50%, EGCG suppressed proliferation of all cell lines by 50%. ECG was even more potent: it inhibited DU145, HH870, HH450 and HH639 cells at concentrations of 24, 27, 29 and 30 µM, whereas EGCG inhibited DU145, HH870, HH450 and HH639 cells at concentrations 89, 45, 62 and 42 µM. When compared with EGCG, ECG more effectively suppresses the growth of prostate cancer and epithelial ovarian cancer cell lines derived from tumors of patients with different stages of disease.",2006 Jun 25,"['Ravindranath, Mepur H.', 'Saravanan, Thiruverkadu S.', 'Monteclaro, Clarence C.', 'Presser, Naftali', 'Ye, Xing', 'Selvan, Senthamil R.', 'Brosman, Stanley']",Evid Based Complement Alternat Med,,,True
52ad224b03765bb748a346a5d0586beef490a490,PMC,The effects of ozone on immune function.,,PMC1518840,7614952,NO-CC CODE,"A review of the literature reveals that ozone (O3) exposure can either suppress or enhance immune responsiveness. These disparate effects elicited by O3 exposure depend, in large part, on the experimental design used, the immune parameters examined as well as the animal species studied. Despite the apparent contradictions, a general pattern of response to O3 exposure can be recognized. Most studies indicate that continuous O3 exposure leads to an early (days 0-3) impairment of immune responsiveness followed, with continued exposures, by a form of adaptation to O3 that results in a re-establishment of the immune response. The effects of O3 exposure on the response to antigenic stimulation also depend on the time at which O3 exposure occurred. Whereas O3 exposure prior to immunization is without effect on the response to antigen, O3 exposure subsequent to immunization suppresses the response to antigen. Although most studies have focused on immune responses in the lung, numerous investigators have provided functional and anatomical evidence to support the hypothesis that O3 exposure can have profound effects on systemic immunity.",1995 Mar,"['Jakab, G J', 'Spannhake, E W', 'Canning, B J', 'Kleeberger, S R', 'Gilmour, M I']",Environ Health Perspect,,,True
833f392ae03b75260838505b490da16d13088cba,PMC,Technical Report Abstracts: TR-335 to TR-364,,PMC1519403,,NO-CC CODE,,1993 Apr,,Environ Health Perspect,,,True
cf3640a2e06457c47beac679ac651bc69f7c9521,PMC,Common commercial cosmetic products induce arthritis in the DA rat.,,PMC1532946,9417771,NO-CC CODE,"Many different agents, including mineral oil and silicone, have the capacity to act as immunological adjuvants, i.e., they can contribute to the activation of the immune system. Some adjuvants, including mineral oil, are known to induce arthritis in certain strains of rats after intradermal injection or percutaneous application. The aim of this study was to determine if common commercial cosmetic products containing mineral oil could induce arthritis in the highly susceptible DA (Dark Agouti) rat. Intradermal injection of five out of eight assayed cosmetic products without further additives resulted in arthritis with synovitis. One of the products induced a very aggressive arthritis, which had declined after 5-9 weeks. When this product was also assayed for arthritogenicity upon percutaneous administration, it induced a mild and transient arthritis in 5 out of 10 DA rats, whereas control animals showed no clinical signs of joint involvement. No arthritic reaction was seen in rats after peroral feeding with the most arthritogenic product or by intravaginal application of Freund's adjuvants. Silicone gel implants in DA rats did not cause arthritis. We conclude that mineral oils included in common commercially available products retain their adjuvant properties and are arthritogenic in the presently investigated arthritis-prone rat strain. There is yet no evidence that mineral oils present in cosmetics may contribute to arthritis in humans, but we suggest that this question should be subject to further investigation.",1998 Jan,"['Sverdrup, B', 'Klareskog, L', 'Kleinau, S']",Environ Health Perspect,,,True
9ef828a2fe98eb0aebae134bd073051c659a8560,PMC,siVirus: web-based antiviral siRNA design software for highly divergent viral sequences,http://dx.doi.org/10.1093/nar/gkl214,PMC1538817,16845046,NO-CC CODE,"siVirus () is a web-based online software system that provides efficient short interfering RNA (siRNA) design for antiviral RNA interference (RNAi). siVirus searches for functional, off-target minimized siRNAs targeting highly conserved regions of divergent viral sequences. These siRNAs are expected to resist viral mutational escape, since their highly conserved targets likely contain structurally/functionally constrained elements. siVirus will be a useful tool for designing optimal siRNAs targeting highly divergent pathogens, including human immunodeficiency virus (HIV), hepatitis C virus (HCV), influenza virus and SARS coronavirus, all of which pose enormous threats to global human health.",2006 Jul 1,"['Naito, Yuki', 'Ui-Tei, Kumiko', 'Nishikawa, Toru', 'Takebe, Yutaka', 'Saigo, Kaoru']",Nucleic Acids Res,,,True
86137493357f000507e97acf40e74d2fdf8039a4,PMC,Nearest neighbor parameters for Watson–Crick complementary heteroduplexes formed between 2′-O-methyl RNA and RNA oligonucleotides,http://dx.doi.org/10.1093/nar/gkl232,PMC1540717,16870722,NO-CC CODE,"Results from optical melting studies of Watson–Crick complementary heteroduplexes formed between 2′-O-methyl RNA and RNA oligonucleotides are used to determine nearest neighbor thermodynamic parameters for predicting the stabilities of such duplexes. The results are consistent with the physical model assumed by the individual nearest neighbor-hydrogen bonding model, which contains terms for helix initiation, base pair stacking and base pair composition. The sequence dependence is similar to that for Watson–Crick complementary RNA/RNA duplexes, which suggests that the sequence dependence may also be similar to that for other backbones that favor A-form RNA conformations.",2006 Jul 26,"['Kierzek, Elzbieta', 'Mathews, David H.', 'Ciesielska, Anna', 'Turner, Douglas H.', 'Kierzek, Ryszard']",Nucleic Acids Res,,,True
927d61c8c5d2d7c892a9f11a454ec80e43b0f46a,PMC,Clinical review: A systematic review of corticosteroid use in infections,http://dx.doi.org/10.1186/cc3904,PMC1550829,16356204,NO-CC CODE,"Traditional teaching suggests that corticosteroids should be avoided during acute infectious episodes for fear of compromising the immune response. However, the outcome benefit shown through steroid administration in early septic shock implies this paranoia may be misplaced. We therefore performed a systematic review of the literature to identify the current strength of evidence for the use of corticosteroids in specified infections, and to make appropriate graded recommendations.",2006 Nov 22,"['Aberdein, Jody', 'Singer, Mervyn']",Crit Care,,,True
1a6dfebcc7315a03ee559aec809e9c7591833999,PMC,"Recently published papers: pulmonary care, pandemics, and eugenics in surviving sepsis?",http://dx.doi.org/10.1186/cc4820,PMC1550845,16469134,NO-CC CODE,"Respiratory failure is one of the leading admission diagnoses on the critical care unit, and the journals have reflected this over the past few months. An understanding of the aetiology of pulmonary sepsis is important but your choice of ventilator gas humidification system is not. There are prophecies of more pandemics, but panic is futile because survival is all down to your genes.",2006 Feb 1,"['Bouch, Christopher', 'Williams, Gareth']",Crit Care,,,True
25850a7f18984f720731456ef16942a48c6f14a8,PMC,Epidemiology studies in critical care,http://dx.doi.org/10.1186/cc4897,PMC1550877,16606434,NO-CC CODE,"Epidemiology studies are an essential part of clinical research, often forming the foundation for studies ranked more highly in the hierarchy of evidence-based medicine. Studies of sepsis to date have been conducted on local, regional, national and international scales, with the majority conducted in the past 5 years. Longitudinal epidemiology studies convey an important additional aspect of the healthcare burden from disease, and may additionally serve to compare the effectiveness and efficiency of healthcare systems, to examine specific patient care strategies and to perform quality control analyses.",2006 Apr 4,"Martin, Greg",Crit Care,,,True
485388f5e7b0617fafb36828bf59032f438a36a7,PMC,"26th International Symposium on Intensive Care and Emergency Medicine, 21–24 March 2006, Brussels, Belgium",http://dx.doi.org/10.1186/cc4935,PMC1550926,16732901,NO-CC CODE,,2006 May 18,"Wurz, Jeannie",Crit Care,,,False
03c813ffcf340b594f76c6005c7cec594d9f4263,PMC,"26th International Symposium on Intensive Care and Emergency Medicine, 21–24 March 2006, Brussels, Belgium",http://dx.doi.org/10.1186/cc4935,PMC1550926,16732901,NO-CC CODE,,2006 May 18,"Wurz, Jeannie",Crit Care,,,False
72af637abdc92f045426ef76b39818510cd5053a,PMC,"Year in review 2005: Critical Care – Respirology: mechanical ventilation, infection, monitoring, and education",http://dx.doi.org/10.1186/cc4959,PMC1550947,16817943,NO-CC CODE,"We summarize all original research in the field of respiratory intensive care medicine published in 2005 in Critical Care. Twenty-seven articles were grouped into the following categories and subcategories to facilitate rapid overview: mechanical ventilation (physiology, spontaneous breathing during mechanical ventilation, high frequency oscillatory ventilation, side effects of mechanical ventilation, sedation, and prone positioning); infection (pneumonia and sepsis); monitoring (ventilatory monitoring, pulmonary artery catheter and pulse oxymeter); and education (training and health outcome).",2006 Jun 29,"['Haitsma, Jack J', 'Villar, Jesús', 'Slutsky, Arthur S']",Crit Care,,,True
f7929dc28f24ccdc65e36f6b67d182adc6c4f2ba,PMC,Targeted Delivery of siRNA,http://dx.doi.org/10.1155/JBB/2006/63675,PMC1559924,17057365,NO-CC CODE,"Therapeutic application of siRNA requires delivery to the correct intracellular location, to interact with the RNAi machinery within the target cell, within the target tissue responsible for the pathology. Each of these levels of targeting poses a significant barrier. To overcome these barriers several strategies have been developed, such as chemical modifications of siRNA, viral nucleic acid delivery systems, and nonviral nucleic acid delivery systems. Here, we discuss progress that has been made to improve targeted delivery of siRNA in vivo for each of these strategies.",2006 Jun 25,"['Oliveira, Sabrina', 'Storm, Gert', 'Schiffelers, Raymond M.']",J Biomed Biotechnol,,,True
f4d18f2beafa875cd4e30a9a237a64b9d3110856,PMC,Delivery Systems for the Direct Application of siRNAs to Induce        RNA Interference (RNAi) In Vivo,http://dx.doi.org/10.1155/JBB/2006/71659,PMC1559929,17057369,NO-CC CODE,"RNA interference (RNAi) is a powerful method for specific gene silencing which may also lead to promising novel therapeutic strategies. It is mediated through small interfering RNAs (siRNAs) which sequence-specifically trigger the cleavage and subsequent degradation of their target mRNA. One critical factor is the ability to deliver intact siRNAs into target cells/organs in vivo. This review highlights the mechanism of RNAi and the guidelines for the design of optimal siRNAs. It gives an overview of studies based on the systemic or local application of naked siRNAs or the use of various nonviral siRNA delivery systems. One promising avenue is the the complexation of siRNAs with the polyethylenimine (PEI), which efficiently stabilizes siRNAs and, upon systemic administration, leads to the delivery of the intact siRNAs into different organs. The antitumorigenic effects of PEI/siRNA-mediated in vivo gene-targeting of tumor-relevant proteins like in mouse tumor xenograft models are described.",2006 May 18,"Aigner, Achim",J Biomed Biotechnol,,,True
8ae137c8da1607b3a8e4c946c07ca8bda67f88ac,PMC,Discovering human history from stomach bacteria,http://dx.doi.org/10.1186/gb-2003-4-5-213,PMC156578,12734001,NO-CC CODE,Recent analyses of human pathogens have revealed that their evolutionary histories are congruent with the hypothesized pattern of ancient and modern human population migrations. Phylogenetic trees of strains of the bacterium Helicobacter pylori and the polyoma JC virus taken from geographically diverse groups of human beings correlate closely with relationships of the populations in which they are found.,2003 Apr 28,"Disotell, Todd R",Genome Biol,,,True
384c14fbb8287badd7f0f1823ea34b6cc4ab86cb,PMC,Microbiological safety of drinking water: United States and global perspectives.,,PMC1566363,10229718,NO-CC CODE,"Waterborne disease statistics only begin to estimate the global burden of infectious diseases from contaminated drinking water. Diarrheal disease is dramatically underreported and etiologies seldom diagnosed. This review examines available data on waterborne disease incidence both in the United States and globally together with its limitations. The waterborne route of transmission is examined for bacterial, protozoal, and viral pathogens that either are frequently associated with drinking water (e.g., Shigella spp.), or for which there is strong evidence implicating the waterborne route of transmission (e.g., Leptospira spp.). In addition, crucial areas of research are discussed, including risks from selection of treatment-resistant pathogens, importance of environmental reservoirs, and new methodologies for pathogen-specific monitoring. To accurately assess risks from waterborne disease, it is necessary to understand pathogen distribution and survival strategies within water distribution systems and to apply methodologies that can detect not only the presence, but also the viability and infectivity of the pathogen.",1999 Feb,"Ford, T E",Environ Health Perspect,,,True
3b5579588b12f1f4bd5e6c1eea4c8ba0258a4f57,PMC,Infectious diseases of the upper respiratory tract: implications for toxicology studies.,,PMC1568352,2200664,NO-CC CODE,"The consequences of adventitious infectious agents upon the interpretation of toxicology studies performed in rats and mice are incompletely understood. Several prevalent murine pathogens cause alterations of the respiratory system that can confuse the assessment of chemically induced airway injury. In some instances the pathogenesis of infection with these agents has been relatively well studied in the lower respiratory tract. However, there are few well-controlled studies that have examined the upper respiratory region, which result in interpretive problems for toxicologic pathologists. The conduct and interpretation of both short-term and chronic rodent bioassays can be compromised by both the clinical and subclinical manifestations of infectious diseases. This paper reviews several important infectious diseases of the upper airway of rats and mice and discusses the potential influence of these conditions on the results of toxicology studies.",1990 Apr,"['Everitt, J I', 'Richter, C B']",Environ Health Perspect,,,True
ac20dcb832b6cd6ea92dd87915d8520a91cef2b2,PMC,Report of the Federal Panel on Formaldehyde.,,PMC1568898,6977445,NO-CC CODE,"The Federal Panel on Formaldehyde concluded that definitive experiments exist which demonstrate the mutagenicity and carcinogenicity of formaldehyde under laboratory conditions. Formaldehyde induces both gene mutations and chromosomal aberrations in a variety of test systems. Inhalation of formaldehyde causes cancer of the nose in rats. The concentrations of formaldehyde in inhaled air that caused nasal cancer in Fisher 344 rats are within the same order of magnitude as those to which humans may be exposed. The data presently available do not permit a direct assessment of the carcinogenicity of formaldehyde to man. Epidemiologic studies on exposed human populations are in progress and may further clarify the situation. Other experimental and human studies on toxic effects such as teratogenicity and reproductive disorders are as yet inadequate for a health risk assessment. The CIIT 24 month study on animal carcinogenicity has not yet been completely evaluated. Additional data are expected on the effects of prolonged exposure to lower doses of formaldehyde and on the possible carcinogenicity of formaldehyde in the mouse. The panel recommends that, for a comprehensive health risk assessment, further experiments be conducted on the effects of other modes of exposure (ingestion and skin penetration), the effects in humans, and on the pharmacokinetics of formaldehyde in man and animals and the possible role for formaldehyde in reproductive and chronic respiratory disorders. It is the conclusion of the panel that formaldehyde should be presumed to pose a carcinogenic risk to humans.",1982 Feb,,Environ Health Perspect,,,True
f0487c3f285a07a594aac45ed339968de0680c3f,PMC,Combining genetic and biochemical approaches to identify functional molecular contact points,http://dx.doi.org/10.1251/bpo121,PMC1592461,17033698,NO-CC CODE,"Protein-protein interactions are required for many viral and cellular functions and are potential targets for novel therapies. Here we detail a series of genetic and biochemical techniques used in combination to find an essential molecular contact point on the duck hepatitis B virus polymerase. These techniques include differential immunoprecipitation, mutagenesis and peptide competition. The strength of these techniques is their ability to identify contact points on intact proteins or protein complexes employing functional assays. This approach can be used to aid identification of putative binding sites on proteins and protein complexes which are resistant to characterization by other methods.",2006 Aug 10,"['Badtke, Matthew P.', 'Cao, Feng', 'Tavis, John E.']",Biol Proced Online,,,True
8d3800d0ab71b59ea6a298927762a3fd09655107,PMC,Anaplasma phagocytophilum Infection in North Norway. The First Laboratory Confirmed Case,http://dx.doi.org/10.1186/1751-0147-46-167,PMC1624813,16261930,NO-CC CODE,,2005 Sep 30,"['Stuen, S', 'Oppegaard, A Solli', 'Bergström, K', 'Moum, T']",Acta Vet Scand,,,True
ab394df8160904be82c09bfacf72f690a8004a0c,PMC,Epitope-based vaccines: SARS – a model,http://dx.doi.org/10.1186/1742-4690-3-S1-P62,PMC1716885,,NO-CC CODE,,2006 Dec 21,"['Freund, Natalia Tarnovitski', 'Sui, Jianhua', 'Marasco, Wayne A', 'Gershoni, Jonathan M']",Retrovirology,,,True
3899c3b15d80afef1944752dafbebaa99ee43187,PMC,A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice,http://dx.doi.org/10.1371/journal.ppat.0030005,PMC1769406,17222058,NO-CC CODE,"No single animal model for severe acute respiratory syndrome (SARS) reproduces all aspects of the human disease. Young inbred mice support SARS-coronavirus (SARS-CoV) replication in the respiratory tract and are available in sufficient numbers for statistical evaluation. They are relatively inexpensive and easily accessible, but their use in SARS research is limited because they do not develop illness following infection. Older (12- to 14-mo-old) BALB/c mice develop clinical illness and pneumonitis, but they can be hard to procure, and immune senescence complicates pathogenesis studies. We adapted the SARS-CoV (Urbani strain) by serial passage in the respiratory tract of young BALB/c mice. Fifteen passages resulted in a virus (MA15) that is lethal for mice following intranasal inoculation. Lethality is preceded by rapid and high titer viral replication in lungs, viremia, and dissemination of virus to extrapulmonary sites accompanied by lymphopenia, neutrophilia, and pathological changes in the lungs. Abundant viral antigen is extensively distributed in bronchial epithelial cells and alveolar pneumocytes, and necrotic cellular debris is present in airways and alveoli, with only mild and focal pneumonitis. These observations suggest that mice infected with MA15 die from an overwhelming viral infection with extensive, virally mediated destruction of pneumocytes and ciliated epithelial cells. The MA15 virus has six coding mutations associated with adaptation and increased virulence; when introduced into a recombinant SARS-CoV, these mutations result in a highly virulent and lethal virus (rMA15), duplicating the phenotype of the biologically derived MA15 virus. Intranasal inoculation with MA15 reproduces many aspects of disease seen in severe human cases of SARS. The availability of the MA15 virus will enhance the use of the mouse model for SARS because infection with MA15 causes morbidity, mortality, and pulmonary pathology. This virus will be of value as a stringent challenge in evaluation of the efficacy of vaccines and antivirals.",2007 Jan 12,"['Roberts, Anjeanette', 'Deming, Damon', 'Paddock, Christopher D', 'Cheng, Aaron', 'Yount, Boyd', 'Vogel, Leatrice', 'Herman, Brian D', 'Sheahan, Tim', 'Heise, Mark', 'Genrich, Gillian L', 'Zaki, Sherif R', 'Baric, Ralph', 'Subbarao, Kanta']",PLoS Pathog,,,True
635deef7edf38573fceb916e49b70330b3ff2037,PMC,A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice,http://dx.doi.org/10.1371/journal.ppat.0030005,PMC1769406,17222058,NO-CC CODE,"No single animal model for severe acute respiratory syndrome (SARS) reproduces all aspects of the human disease. Young inbred mice support SARS-coronavirus (SARS-CoV) replication in the respiratory tract and are available in sufficient numbers for statistical evaluation. They are relatively inexpensive and easily accessible, but their use in SARS research is limited because they do not develop illness following infection. Older (12- to 14-mo-old) BALB/c mice develop clinical illness and pneumonitis, but they can be hard to procure, and immune senescence complicates pathogenesis studies. We adapted the SARS-CoV (Urbani strain) by serial passage in the respiratory tract of young BALB/c mice. Fifteen passages resulted in a virus (MA15) that is lethal for mice following intranasal inoculation. Lethality is preceded by rapid and high titer viral replication in lungs, viremia, and dissemination of virus to extrapulmonary sites accompanied by lymphopenia, neutrophilia, and pathological changes in the lungs. Abundant viral antigen is extensively distributed in bronchial epithelial cells and alveolar pneumocytes, and necrotic cellular debris is present in airways and alveoli, with only mild and focal pneumonitis. These observations suggest that mice infected with MA15 die from an overwhelming viral infection with extensive, virally mediated destruction of pneumocytes and ciliated epithelial cells. The MA15 virus has six coding mutations associated with adaptation and increased virulence; when introduced into a recombinant SARS-CoV, these mutations result in a highly virulent and lethal virus (rMA15), duplicating the phenotype of the biologically derived MA15 virus. Intranasal inoculation with MA15 reproduces many aspects of disease seen in severe human cases of SARS. The availability of the MA15 virus will enhance the use of the mouse model for SARS because infection with MA15 causes morbidity, mortality, and pulmonary pathology. This virus will be of value as a stringent challenge in evaluation of the efficacy of vaccines and antivirals.",2007 Jan 12,"['Roberts, Anjeanette', 'Deming, Damon', 'Paddock, Christopher D', 'Cheng, Aaron', 'Yount, Boyd', 'Vogel, Leatrice', 'Herman, Brian D', 'Sheahan, Tim', 'Heise, Mark', 'Genrich, Gillian L', 'Zaki, Sherif R', 'Baric, Ralph', 'Subbarao, Kanta']",PLoS Pathog,,,False
72ca641edaef238e49b5f2dd299defb51fae3dd1,PMC,A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice,http://dx.doi.org/10.1371/journal.ppat.0030005,PMC1769406,17222058,NO-CC CODE,"No single animal model for severe acute respiratory syndrome (SARS) reproduces all aspects of the human disease. Young inbred mice support SARS-coronavirus (SARS-CoV) replication in the respiratory tract and are available in sufficient numbers for statistical evaluation. They are relatively inexpensive and easily accessible, but their use in SARS research is limited because they do not develop illness following infection. Older (12- to 14-mo-old) BALB/c mice develop clinical illness and pneumonitis, but they can be hard to procure, and immune senescence complicates pathogenesis studies. We adapted the SARS-CoV (Urbani strain) by serial passage in the respiratory tract of young BALB/c mice. Fifteen passages resulted in a virus (MA15) that is lethal for mice following intranasal inoculation. Lethality is preceded by rapid and high titer viral replication in lungs, viremia, and dissemination of virus to extrapulmonary sites accompanied by lymphopenia, neutrophilia, and pathological changes in the lungs. Abundant viral antigen is extensively distributed in bronchial epithelial cells and alveolar pneumocytes, and necrotic cellular debris is present in airways and alveoli, with only mild and focal pneumonitis. These observations suggest that mice infected with MA15 die from an overwhelming viral infection with extensive, virally mediated destruction of pneumocytes and ciliated epithelial cells. The MA15 virus has six coding mutations associated with adaptation and increased virulence; when introduced into a recombinant SARS-CoV, these mutations result in a highly virulent and lethal virus (rMA15), duplicating the phenotype of the biologically derived MA15 virus. Intranasal inoculation with MA15 reproduces many aspects of disease seen in severe human cases of SARS. The availability of the MA15 virus will enhance the use of the mouse model for SARS because infection with MA15 causes morbidity, mortality, and pulmonary pathology. This virus will be of value as a stringent challenge in evaluation of the efficacy of vaccines and antivirals.",2007 Jan 12,"['Roberts, Anjeanette', 'Deming, Damon', 'Paddock, Christopher D', 'Cheng, Aaron', 'Yount, Boyd', 'Vogel, Leatrice', 'Herman, Brian D', 'Sheahan, Tim', 'Heise, Mark', 'Genrich, Gillian L', 'Zaki, Sherif R', 'Baric, Ralph', 'Subbarao, Kanta']",PLoS Pathog,,,False
42d0cbae854328376847605927593412b399c6bd,PMC,A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice,http://dx.doi.org/10.1371/journal.ppat.0030005,PMC1769406,17222058,NO-CC CODE,"No single animal model for severe acute respiratory syndrome (SARS) reproduces all aspects of the human disease. Young inbred mice support SARS-coronavirus (SARS-CoV) replication in the respiratory tract and are available in sufficient numbers for statistical evaluation. They are relatively inexpensive and easily accessible, but their use in SARS research is limited because they do not develop illness following infection. Older (12- to 14-mo-old) BALB/c mice develop clinical illness and pneumonitis, but they can be hard to procure, and immune senescence complicates pathogenesis studies. We adapted the SARS-CoV (Urbani strain) by serial passage in the respiratory tract of young BALB/c mice. Fifteen passages resulted in a virus (MA15) that is lethal for mice following intranasal inoculation. Lethality is preceded by rapid and high titer viral replication in lungs, viremia, and dissemination of virus to extrapulmonary sites accompanied by lymphopenia, neutrophilia, and pathological changes in the lungs. Abundant viral antigen is extensively distributed in bronchial epithelial cells and alveolar pneumocytes, and necrotic cellular debris is present in airways and alveoli, with only mild and focal pneumonitis. These observations suggest that mice infected with MA15 die from an overwhelming viral infection with extensive, virally mediated destruction of pneumocytes and ciliated epithelial cells. The MA15 virus has six coding mutations associated with adaptation and increased virulence; when introduced into a recombinant SARS-CoV, these mutations result in a highly virulent and lethal virus (rMA15), duplicating the phenotype of the biologically derived MA15 virus. Intranasal inoculation with MA15 reproduces many aspects of disease seen in severe human cases of SARS. The availability of the MA15 virus will enhance the use of the mouse model for SARS because infection with MA15 causes morbidity, mortality, and pulmonary pathology. This virus will be of value as a stringent challenge in evaluation of the efficacy of vaccines and antivirals.",2007 Jan 12,"['Roberts, Anjeanette', 'Deming, Damon', 'Paddock, Christopher D', 'Cheng, Aaron', 'Yount, Boyd', 'Vogel, Leatrice', 'Herman, Brian D', 'Sheahan, Tim', 'Heise, Mark', 'Genrich, Gillian L', 'Zaki, Sherif R', 'Baric, Ralph', 'Subbarao, Kanta']",PLoS Pathog,,,False
9795fe49f827ff0654ce919cd8b7450e8a2b40d8,PMC,The immunoregulatory and allergy-associated cytokines in the aetiology of the otitis media with effusion.,http://dx.doi.org/10.1080/09629350410001688477,PMC1781541,15203548,NO-CC CODE,"Inflammation in the middle ear mucosa, which can be provoked by different primary factors such as bacterial and viral infection, local allergic reactions and reflux, is the crucial event in the pathogenesis of otitis media with effusion (OME). Unresolved acute inflammatory responses or defective immunoregulation of middle inflammation can promote chronic inflammatory processes and stimulate the chronic condition of OME. Cytokines are the central molecular regulators of middle ear inflammation and can switch the acute phase of inflammation in the chronic stage and induce molecular-pathological processes leading to the histopathological changes accompanying OME. In this review we present cytokines identified in otitis media, immunoregulatory [interleukin (IL)-2, IL-10, transforming growth factor-beta]) and allergy associated (IL-4, IL-5, granulocyte-macrophage colony-stimulating factor), as crucial molecular regulators, responsible for chronic inflammation in the middle ear and the chronic condition of OME.",2004 Apr,"['Smirnova, Marina G', 'Birchall, John P', 'Pearson, Jeffrey P']",Mediators Inflamm,,,True
ec01394568507c47b7ef63f688ca9ca4c233964a,PMC,Viral and Bacterial Pathogens in Bovine Respiratory Disease in Finland,http://dx.doi.org/10.1186/1751-0147-45-193,PMC1820993,15663079,NO-CC CODE,"Pathogens causing bovine respiratory tract disease in Finland were investigated. Eighteen cattle herds with bovine respiratory disease were included. Five diseased calves from each farm were chosen for closer examination and tracheobronchial lavage. Blood samples were taken from the calves at the time of the investigation and from 86 calves 3–4 weeks later. In addition, 6–10 blood samples from animals of different ages were collected from each herd, resulting in 169 samples. Serum samples were tested for antibodies to bovine parainfluenza virus-3 (PIV-3), bovine respiratory syncytial virus (BRSV), bovine coronavirus (BCV), bovine adenovirus-3 (BAV-3) and bovine adenovirus-7 (BAV-7). About one third of the samples were also tested for antibodies to bovine virus diarrhoea virus (BVDV) with negative results. Bacteria were cultured from lavage fluid and in vitro susceptibility to selected antimicrobials was tested. According to serological findings, PIV-3, BAV-7, BAV-3, BCV and BRSV are common pathogens in Finnish cattle with respiratory problems. A titre rise especially for BAV-7 and BAV-3, the dual growth of Mycoplasma dispar and Pasteurella multocida, were typical findings in diseased calves. Pasteurella sp. strains showed no resistance to tested antimicrobials. Mycoplasma bovis and Mannheimia haemolytica were not found.",2004 Dec 31,"['Härtel, H', 'Nikunen, S', 'Neuvonen, E', 'Tanskanen, R', 'Kivelä, S-L', 'Aho, P', 'Soveri, T', 'Saloniemi, H']",Acta Vet Scand,,,True
9e8066b614f3db5212ebd32729dff2430cfc988a,PMC,Studies on Calf Diarrhoea in Mozambique: Prevalence of Bacterial Pathogens,http://dx.doi.org/10.1186/1751-0147-45-27,PMC1821001,15535084,NO-CC CODE,"The prevalence of diarrhoea in calves was investigated in 8 dairy farms in Mozambique at 4 occasions during 2 consecutive years. A total of 1241 calves up to 6 months of age were reared in the farms, and 63 (5%) of them had signs of diarrhoea. Two farms had an overall higher prevalence (13% and 21%) of diarrhoea. Faecal samples were collected from all diarrhoeal calves (n = 63) and from 330 healthy calves and analysed for Salmonella species, Campylobacter jejuni and enterotoxigenic Escherichia coli (ETEC). Salmonella spp. was isolated in only 2% of all calves. Campylobacter was isolated in 11% of all calves, irrespective of health condition, and was more frequent (25%) in one of the 2 diarrhoeal farms (p = 0.001). 80% of the isolates were identified as C. jejuni. No ETEC strains were detected among the 55 tested strains from diarrhoeal calves, but 22/55 (40%) strains from diarrhoeal calves and 14/88 (16%) strains from healthy calves carried the K99 adhesin (p = 0.001). 6,757 E. coli isolates were typed with a biochemical fingerprinting method (the PhenePlate™) giving the same E. coli diversity in healthy and diarrhoeal calves. Thus it was concluded: i) the overall prevalence of diarrhoea was low, but 2 farms had a higher prevalence that could be due to an outbreak situation, ii) Salmonella did not seem to be associated with diarrhoea, iii) Campylobacter jejuni was common at one of the 2 diarrhoeal farms and iv) ETEC strains were not found, but K99 antigen was more prevalent in E. coli strains from diarrhoeal calves than from healthy, as well as more prevalent in one diarrhoeal farm.",2004 Mar 31,"['Achá, SJ', 'Kühn, I', 'Jonsson, P', 'Mbazima, G', 'Katouli, M', 'Möllby, R']",Acta Vet Scand,,,True
5f4a9c2d6e1f0256ef7c1088f61809fcc6af5734,PMC,"The Role of Internists During Epidemics, Outbreaks, and Bioterrorist Attacks",http://dx.doi.org/10.1007/s11606-006-0030-2,PMC1824729,17351853,NO-CC CODE,"Internists are well-positioned to play significant roles in recognizing and responding to epidemics, outbreaks, and bioterrorist attacks. They see large numbers of patients with various health problems and may be the patients’ only interaction with the medical community for symptoms resulting from infectious diseases and injuries from radiation, chemicals, and/or burns. Therefore, Internists must understand early warning signs of different bioterrorist and infectious agents, proper reporting channels and measures, various ways that they can assist the public health response, and roles of different local, state, and federal agencies. In addition, it is important to understand effects of a public health disaster on clinic operations and relevant legal consequences.",2007 Jan 13,"Lee, Bruce Y.",J Gen Intern Med,,,True
a510ff06475118256003b81fbc9abdaa33242da1,PMC,"No Effect of a Homeopathic Preparation on Neonatal Calf Diarrhoea in a Randomised Double-Blind, Placebo-Controlled Clinical Trial",http://dx.doi.org/10.1186/1751-0147-44-97,PMC1831551,14650548,NO-CC CODE,"A double-blind, placebo-controlled clinical trial of a homeopathic treatment of neonatal calf diarrhoea was performed using 44 calves in 12 dairy herds. Calves with spontaneously derived diarrhoea were treated with either the homeopathic remedy Podophyllum (D30) (n = 24) or a placebo (n = 20). No clinically or statistically significant difference between the 2 groups was demonstrated. Calves treated with Podophyllum had an average of 3.1 days of diarrhoea compared with 2.9 days for the placebo group. Depression, inappetence and fever were presented equally in the 2 groups. These results support the widely held opinion that scientific proof for the efficacy of veterinary homeopathy is lacking. In the European Union this implies a considerable risk for animal welfare, since in some countries priority is given to homeopathic treatments in organic farming.",2003 Jun 30,"['de Verdier, K', 'Öhagen, P', 'Alenius, S']",Acta Vet Scand,,,True
c905423410ad459a067d65c11efbb89fa196d751,PMC,Cryptosporidium parvum and Giardia intestinalis in Calf Diarrhoea in Sweden,http://dx.doi.org/10.1186/1751-0147-44-145,PMC1831560,15074627,NO-CC CODE,"The objective of this study conducted in 75 herds was to investigate the presence and significance of Cryptosporidium parvum and Giardia intestinalis in Swedish dairy calves in comparison with rotavirus, coronavirus and Escherichia coli K99+. The farmers were asked to collect faecal samples from each heifer calf that had diarrhoea between birth and 90 days of age, and also from a healthy calf of the same age. In total, 270 samples were collected and analysed. C. parvum, either alone or together with G. intestinalis and/or rotavirus, was detected in 16 (11%) and 6 (5%) of the samples from diarrhoeic and healthy calves, respectively. Even though a higher proportion of diarrhoeic calves shed C. parvum, the difference between the groups was not statistically significant (p = 0.067), possibly due to the low number of positive samples. G. intestinalis was found in 42 (29%) of the diarrhoea samples and in 29 (23%) of the samples from healthy calves. Rotavirus and coronavirus were demonstrated in 24% and 3% of the diarrhoea samples, respectively, whereas E. coli K99+ was only found in samples from 2 healthy calves. C. parvum and G. intestinalis were found in samples from calves 7 to 84 days of age and during all seasons. The results confirm that C. parvum is present in Swedish dairy herds and might have clinical significance. G. intestinalis was the most common agent found but the importance of this parasite remains unclear. Both parasites have suggested zoonotic potential and thus warrant further attention. In addition, rotavirus is a major pathogen in neonatal enteritis in Sweden, whereas coronavirus and E. coli K99+ seem to be of less importance.",2003 Sep 30,"['Björkman, C', 'Svensson, C', 'Christensson, B', 'de Verdier, K']",Acta Vet Scand,,,True
323ece9056ef7a1d81faf3422e98def1efd38f70,PMC,Immune pathways and defence mechanisms in honey bees Apis mellifera,http://dx.doi.org/10.1111/j.1365-2583.2006.00682.x,PMC1847501,17069638,NO-CC CODE,"Social insects are able to mount both group-level and individual defences against pathogens. Here we focus on individual defences, by presenting a genome-wide analysis of immunity in a social insect, the honey bee Apis mellifera. We present honey bee models for each of four signalling pathways associated with immunity, identifying plausible orthologues for nearly all predicted pathway members. When compared to the sequenced Drosophila and Anopheles genomes, honey bees possess roughly one-third as many genes in 17 gene families implicated in insect immunity. We suggest that an implied reduction in immune flexibility in bees reflects either the strength of social barriers to disease, or a tendency for bees to be attacked by a limited set of highly coevolved pathogens.",2006 Oct 1,"['Evans, J D', 'Aronstein, K', 'Chen, Y P', 'Hetru, C', 'Imler, J-L', 'Jiang, H', 'Kanost, M', 'Thompson, G J', 'Zou, Z', 'Hultmark, D']",Insect Mol Biol,,,True
6ea2532aacbdcea4609067523e9e72fa8cd73200,PMC,Mutational analysis of human CEACAM1: the potential of receptor polymorphism in increasing host susceptibility to bacterial infection,http://dx.doi.org/10.1111/j.1462-5822.2006.00789.x,PMC1859983,16953805,NO-CC CODE,"A common overlapping site on the N-terminal IgV-like domain of human carcinoembryonic antigen (CEA)-related cell adhesion molecules (CEACAMs) is targeted by several important human respiratory pathogens. These include Neisseria meningitidis (Nm) and Haemophilus influenzae (Hi) that can cause disseminated or persistent localized infections. To define the precise structural features that determine the binding of distinct pathogens with CEACAMs, we have undertaken molecular modelling and mutation of the receptor molecules at previously implicated key target residues required for bacterial binding. These include Ser-32, Tyr-34, Val-39, Gln-44 and Gln-89, in addition to Ile-91, the primary docking site for the pathogens. Most, but not all, of these residues located adjacent to each other in a previous N-domain model of human CEACAM1, which was based on REI, CD2 and CD4. In the current studies, we have refined this model based on the mouse CEACAM1 crystal structure, and observe that all of the above residues form an exposed continuous binding region on the N-domain. Examination of the model also suggested that substitution of two of these residues 34 and 89 could affect the accessibility of Ile-91 for ligand binding. By introducing selected mutations at the positions 91, 34 and 89, we confirmed the primary importance of Ile-91 in all bacterial binding to CEACAM1 despite the inter- and intraspecies structural differences between the bacterial CEACAM-binding ligands. The studies further indicated that the efficiency of binding was significantly enhanced for specific strains by mutations such as Y34F and Q89N, which also altered the hierarchy of Nm versus Hi strain binding. These studies imply that distinct polymorphisms in human epithelial CEACAMs have the potential to decrease or increase the risk of infection by the receptor-targeting pathogens.",2007 Feb 1,"['Villullas, Silvia', 'Hill, Darryl J', 'Sessions, Richard B', 'Rea, Jon', 'Virji, Mumtaz']",Cell Microbiol,,,True
17845fc831495c6ed20d436bbab6a7a0c77a48ec,PMC,What is new in otitis media?,http://dx.doi.org/10.1007/s00431-007-0461-8,PMC1876255,17364173,NO-CC CODE,"The “wait and see” approach in acute otitis media (AOM), consisting of postponing the antibiotic administration for a few days, has been advocated mainly to counteract the increased bacterial resistance in respiratory infections. This approach is not justified in children less than 2 years of age and this for several reasons. First, AOM is an acute inflammation of the middle ear caused in about 70% of cases by bacteria. Redness and bulging of the tympanic membrane are characteristic findings in bacterial AOM. Second, AOM is associated with long-term dysfunction of the inflamed eustachian tube (ET), particularly in children less than 2 years of age. In this age group, the small calibre of the ET together with its horizontal direction result in impaired clearance, ventilation and protection of the middle ear. Third, recent prospective studies have shown poor long-term prognosis of AOM in children below 2 years with at least 50% of recurrences and persisting otitis media with effusion (OME) in about 35% 6 months after AOM. Viruses elicit AOM in about 30% of children. A prolonged course of AOM has been observed when bacterial and viral infections are combined because viral infection is also associated with ET dysfunction in young children. Bacterial and viral testing of the nasopharyngeal aspirate is an excellent tool both for initial treatment and recurrence of AOM. Antibiotic treatment of AOM is mandatory in children less than 2 years of age to decrease inflammation in the middle ear but also of the ET particularly during the first episode. The best choice is amoxicillin because of its superior penetration in the middle ear. Streptococci pneumoniae with intermediary bacterial resistance to penicillin are particularly associated with recurrent AOM. Therefore the dosage of amoxicillin should be 90 mg/kg per day in three doses. In recurrent AOM with β-lactamase-producing bacilli, amoxicillin should be associated with clavulanic acid at a dose of 6.4 mg/kg per day. The duration of the treatment is not established yet but 10 days is reasonable for a first episode of AOM. OME may be a precursor initiating AOM but also a complication thereof. OME needs a watchful waiting approach. When associated with deafness for 2–3 months in children over 2 years of age, an antibiotic should be given according to the results of the bacterial resistance in the nasopharyngeal aspirate. The high rate of complications of tympanostomy tube insertion outweighs the beneficial effect on hearing loss. The poor results of this procedure are due to the absence of effects on ET dysfunction. Pneumococcal vaccination has little beneficial effects on recurrent AOM and its use in infants needs further studies. Treatment with amoxicillin is indicated in all children younger than 2 years with a first episode of AOM presenting with redness and bulging of the tympanic membrane. Combined amoxicillin and clavulanic acid should be given in patients with β-lactamase-producing bacteria. The duration of treatment is estimated to be at least 10 days depending on the findings by pneumo-otoscopy and tympanometry. Bacterial and viral testing of the nasopharyngeal aspirate is highly recommended particularly in children in day care centres as well as for regular follow-up. The high recurrence rate is due to the long-lasting dysfunction of the eustachian tube and the immune immaturity of children less than 2 years of age.",2007 Jun 16,"Corbeel, Lucien",Eur J Pediatr,,,True
1f226c5209bbf8cef4fdb1822781967928401850,PMC,A new recruit for the army of the men of death,http://dx.doi.org/10.1186/gb-2003-4-7-113,PMC193621,12844350,NO-CC CODE,"The army of the men of death, in John Bunyan's memorable phrase, has a new recruit, and fear has a new face: a face wearing a surgical mask.",2003 Jun 27,"Petsko, Gregory A",Genome Biol,,,False
bada3cc0577a226694617d77f95ac443c6431969,PMC,DNA Vaccines against Protozoan Parasites: Advances and Challenges,http://dx.doi.org/10.1155/2007/90520,PMC1940056,17710244,NO-CC CODE,"Over the past 15 years, DNA vaccines have gone from a scientific curiosity to one of the most dynamic research field and may offer new alternatives for the control of parasitic diseases such as leishmaniasis and Chagas disease. We review here some of the advances and challenges for the development of DNA vaccines against these diseases. Many studies have validated the concept of using DNA vaccines for both protection and therapy against these protozoan parasites in a variety of mouse models. The challenge now is to translate what has been achieved in these models into veterinary or human vaccines of comparable efficacy. Also, genome-mining and new antigen discovery strategies may provide new tools for a more rational search of novel vaccine candidates.",2007 Jun 24,"Dumonteil, Eric",J Biomed Biotechnol,,,True
c7c4b98517819b787b89bfeee835280593dbf035,PMC,"The Trojan Chicken Study, Minnesota",http://dx.doi.org/10.3201/eid1205.050790,PMC1952212,16704840,NO-CC CODE,We conducted a study in the summer of 2004 at county fairs in the Midwest to investigate the role poultry exhibits have in spreading avian pathogens to humans. A nearly invisible powder (pathogen surrogate) that fluoresces under UV light was surreptitiously sprinkled each day on 1 show bird at each of 2 fairs. A UV light box was used to daily examine the hands of 94 poultry-exhibit participants (blinded regarding UV box results) for up to 4 days during the poultry shows. Enrollment and end-of-study questionnaires collected data on pathogen risk factors. Eight (8.5%) of 94 participants had evidence of fluorescent powder contamination (95% confidence interval 2.76%–14.26%). This contamination and infrequent handwashing practices suggest that county fairs are a possible venue for animal-to-human pathogen transmission.,2006 May,"['Olson, Sandra R.', 'Gray, Gregory C.']",Emerg Infect Dis,,,True
638ce87155f81ea03edcb4e2e16c447550aa8405,PMC,Enhancement of the Pathogenicity of Mouse Hepatitis Virus (MHV1) By Prior Infection of Mice with Certain Leukaemia Agents,,PMC2071161,13899183,NO-CC CODE,,1961 Sep,"Gledhill, A. W.",Br J Cancer,,,True
0104f6ceccf92ae8567a0102f89cbb976969a774,PMC,Association of HLA class I with severe acute respiratory syndrome coronavirus infection,http://dx.doi.org/10.1186/1471-2350-4-9,PMC212558,12969506,NO-CC CODE,"BACKGROUND: The human leukocyte antigen (HLA) system is widely used as a strategy in the search for the etiology of infectious diseases and autoimmune disorders. During the Taiwan epidemic of severe acute respiratory syndrome (SARS), many health care workers were infected. In an effort to establish a screening program for high risk personal, the distribution of HLA class I and II alleles in case and control groups was examined for the presence of an association to a genetic susceptibly or resistance to SARS coronavirus infection. METHODS: HLA-class I and II allele typing by PCR-SSOP was performed on 37 cases of probable SARS, 28 fever patients excluded later as probable SARS, and 101 non-infected health care workers who were exposed or possibly exposed to SARS coronavirus. An additional control set of 190 normal healthy unrelated Taiwanese was also used in the analysis. RESULTS: Woolf and Haldane Odds ratio (OR) and corrected P-value (Pc) obtained from two tails Fisher exact test were used to show susceptibility of HLA class I or class II alleles with coronavirus infection. At first, when analyzing infected SARS patients and high risk health care workers groups, HLA-B*4601 (OR = 2.08, P = 0.04, Pc = n.s.) and HLA-B*5401 (OR = 5.44, P = 0.02, Pc = n.s.) appeared as the most probable elements that may be favoring SARS coronavirus infection. After selecting only a ""severe cases"" patient group from the infected ""probable SARS"" patient group and comparing them with the high risk health care workers group, the severity of SARS was shown to be significantly associated with HLA-B*4601 (P = 0.0008 or Pc = 0.0279). CONCLUSIONS: Densely populated regions with genetically related southern Asian populations appear to be more affected by the spreading of SARS infection. Up until recently, no probable SARS patients were reported among Taiwan indigenous peoples who are genetically distinct from the Taiwanese general population, have no HLA-B* 4601 and have high frequency of HLA-B* 1301. While increase of HLA-B* 4601 allele frequency was observed in the ""Probable SARS infected"" patient group, a further significant increase of the allele was seen in the ""Severe cases"" patient group. These results appeared to indicate association of HLA-B* 4601 with the severity of SARS infection in Asian populations. Independent studies are needed to test these results.",2003 Sep 12,"['Lin, Marie', 'Tseng, Hsiang-Kuang', 'Trejaut, Jean A', 'Lee, Hui-Lin', 'Loo, Jun-Hun', 'Chu, Chen-Chung', 'Chen, Pei-Jan', 'Su, Ying-Wen', 'Lim, Ken Hong', 'Tsai, Zen-Uong', 'Lin, Ruey-Yi', 'Lin, Ruey-Shiung', 'Huang, Chun-Hsiung']",BMC Med Genet,,,True
62b7f419bb3a4af2f439778b85c0b2582461053a,PMC,Nucleolus: the fascinating nuclear body,http://dx.doi.org/10.1007/s00418-007-0359-6,PMC2137947,18046571,NO-CC CODE,"Nucleoli are the prominent contrasted structures of the cell nucleus. In the nucleolus, ribosomal RNAs are synthesized, processed and assembled with ribosomal proteins. RNA polymerase I synthesizes the ribosomal RNAs and this activity is cell cycle regulated. The nucleolus reveals the functional organization of the nucleus in which the compartmentation of the different steps of ribosome biogenesis is observed whereas the nucleolar machineries are in permanent exchange with the nucleoplasm and other nuclear bodies. After mitosis, nucleolar assembly is a time and space regulated process controlled by the cell cycle. In addition, by generating a large volume in the nucleus with apparently no RNA polymerase II activity, the nucleolus creates a domain of retention/sequestration of molecules normally active outside the nucleolus. Viruses interact with the nucleolus and recruit nucleolar proteins to facilitate virus replication. The nucleolus is also a sensor of stress due to the redistribution of the ribosomal proteins in the nucleoplasm by nucleolus disruption. The nucleolus plays several crucial functions in the nucleus: in addition to its function as ribosome factory of the cells it is a multifunctional nuclear domain, and nucleolar activity is linked with several pathologies. Perspectives on the evolution of this research area are proposed.",2008 Jan 29,"['Sirri, Valentina', 'Urcuqui-Inchima, Silvio', 'Roussel, Pascal', 'Hernandez-Verdun, Danièle']",Histochem Cell Biol,,,True
6999b89c08c8a72fc0e86e78e4fd67666516a63a,PMC,World wide web resources on control of nosocomial infections,http://dx.doi.org/10.1186/cc5116,PMC2151856,17254319,NO-CC CODE,"Nosocomial infections are a major worldwide cause of death and disability, infection control programs are effective in limiting these infections, especially those acquired in the intensive care unit. The development of the world wide web has provided health care professionals with immediate access to continuously updated information in the field of infection control. We sought to identify websites that contain information on nosocomial infection control by using popular internet search engines, such as Google, Yahoo and AltaVista, and by reviewing relevant publications identified in the PubMed and Current Contents databases. Only those sites that were English language, open access, and developed by a government, academic institution, or national or international scientific association were eligible for inclusion. From a vast number of internet sites initially identified, we selected 49 that provide information on infection control for inclusion in our list of practical and relevant internet resources. Several sites provide general information on infection control practices, whereas others focus on one or a few specific infection(s). We provide health care professionals with a timely and succinct list of open access internet resources that contain information regarding the prevention and control of nosocomial infections in order to help in the dissemination of relevant information and so contribute to the limitation of such hazards.",2007 Jan 25,"['Siempos, Ilias I', 'Fragoulis, Konstantinos N', 'Falagas, Matthew E']",Crit Care,,,True
c135b16e3b78c0c09c16de6287ddb1233acf9bd3,PMC,Bovine Respiratory Syncytial Virus (BRSV) Pneumonia in Beef Calf Herds Despite Vaccination,http://dx.doi.org/10.1186/1751-0147-42-113,PMC2202333,11455891,NO-CC CODE,"The present report describes the clinical, pathological, serological and virological findings in calves from 2 larger Danish beef herds experiencing outbreaks of pneumonia. The calves had been vaccinated with an inactivated bovine respiratory syncytial virus (BRSV) vaccine 2 months prior to the outbreak. The clinical signs comprised nasal discharge, pyrexia, cough and increased respiratory rates. A total of 28 calves died in the 2 herds. The laboratory investigations revealed that BRSV was involved and probably initiated both outbreaks. Furthermore, the serological results suggested that the vaccine induced only sparse levels of antibodies probably due to the presence of maternally derived antibodies at the time of vaccination. Necropsy findings in 5 calves revealed changes typical for infectious pneumonia with involvment of BRSV. In conclusion, vaccination of calves against BRSV in 2 Danish beef herds failed to protect the calves against severe or even fatal BRSV mediated respiratory disease 2 months later.",2001 Mar 31,"['Larsen, LE', 'Tegtmeier, C', 'Pedersen, E']",Acta Vet Scand,,,True
9c4703d955eb0a06809ef3c48ddb829fe0ef3987,PMC,Clinical review: Update of avian influenza A infections in humans,http://dx.doi.org/10.1186/cc5675,PMC2206439,17419881,NO-CC CODE,"Influenza A viruses have a wide host range for infection, from wild waterfowl to poultry to humans. Recently, the cross-species transmission of avian influenza A, particularly subtype H5N1, has highlighted the importance of the non-human subtypes and their incidence in the human population has increased over the past decade. During cross-species transmission, human disease can range from the asymptomatic to mild conjunctivitis to fulminant pneumonia and death. With these cases, however, the risk for genetic change and development of a novel virus increases, heightening the need for public health and hospital measures. This review discusses the epidemiology, host range, human disease, outcome, treatment, and prevention of cross-transmission of avian influenza A into humans.",2007 Mar 22,"['Sandrock, Christian', 'Kelly, Terra']",Crit Care,,,True
e5a12d970ccbf27a26ddd5568214768342997cc9,PMC,Clinical review: Mass casualty triage – pandemic influenza and critical care,http://dx.doi.org/10.1186/cc5732,PMC2206465,17490495,NO-CC CODE,"Worst case scenarios for pandemic influenza planning in the US involve over 700,000 patients requiring mechanical ventilation. UK planning predicts a 231% occupancy of current level 3 (intensive care unit) bed capacity. Critical care planners need to recognise that mortality is likely to be high and the risk to healthcare workers significant. Contingency planning should, therefore, be multi-faceted, involving a robust health command structure, the facility to expand critical care provision in terms of space, equipment and staff and cohorting of affected patients in the early stages. It should also be recognised that despite this expansion of critical care, demand will exceed supply and a process for triage needs to be developed that is valid, reproducible, transparent and consistent with distributive justice. We advocate the development and validation of physiological scores for use as a triage tool, coupled with candid public discussion of the process.",2007 Apr 30,"['Challen, Kirsty', 'Bentley, Andrew', 'Bright, John', 'Walter, Darren']",Crit Care,,,True
702962623f2e16d33d405327b3de64f6751035b6,PMC,Year in review 2006: Critical Care – paediatrics,http://dx.doi.org/10.1186/cc5946,PMC2206501,17764585,NO-CC CODE,"In 2006, paediatric intensive care-related subjects were discussed in a number of papers published in various journals, including Critical Care. Because they focused on the cardiovascular system and its support, we summarize them here. In particular, these papers highlighted the management of refractory septic shock, extracorporeal support, outcome markers in sepsis, and outcome after cardiac arrest.",2007 Aug 24,"['Amoretti, Carolina F', 'Tasker, Robert C']",Crit Care,,,True
5b68a553a7cbbea13472721cd1ad617d42b40c26,PMC,A double epidemic model for the SARS propagation,http://dx.doi.org/10.1186/1471-2334-3-19,PMC222908,12964944,NO-CC CODE,"BACKGROUND: An epidemic of a Severe Acute Respiratory Syndrome (SARS) caused by a new coronavirus has spread from the Guangdong province to the rest of China and to the world, with a puzzling contagion behavior. It is important both for predicting the future of the present outbreak and for implementing effective prophylactic measures, to identify the causes of this behavior. RESULTS: In this report, we show first that the standard Susceptible-Infected-Removed (SIR) model cannot account for the patterns observed in various regions where the disease spread. We develop a model involving two superimposed epidemics to study the recent spread of the SARS in Hong Kong and in the region. We explore the situation where these epidemics may be caused either by a virus and one or several mutants that changed its tropism, or by two unrelated viruses. This has important consequences for the future: the innocuous epidemic might still be there and generate, from time to time, variants that would have properties similar to those of SARS. CONCLUSION: We find that, in order to reconcile the existing data and the spread of the disease, it is convenient to suggest that a first milder outbreak protected against the SARS. Regions that had not seen the first epidemic, or that were affected simultaneously with the SARS suffered much more, with a very high percentage of persons affected. We also find regions where the data appear to be inconsistent, suggesting that they are incomplete or do not reflect an appropriate identification of SARS patients. Finally, we could, within the framework of the model, fix limits to the future development of the epidemic, allowing us to identify landmarks that may be useful to set up a monitoring system to follow the evolution of the epidemic. The model also suggests that there might exist a SARS precursor in a large reservoir, prompting for implementation of precautionary measures when the weather cools down.",2003 Sep 10,"['Ng, Tuen Wai', 'Turinici, Gabriel', 'Danchin, Antoine']",BMC Infect Dis,,,True
3ed670f60a7be2e3e2a991ea8af1fdd5fa5e2b2c,PMC,Cloaked similarity between HIV-1 and SARS-CoV suggests an anti-SARS strategy,http://dx.doi.org/10.1186/1471-2180-3-20,PMC222911,14499001,NO-CC CODE,"BACKGROUND: Severe acute respiratory syndrome (SARS) is a febrile respiratory illness. The disease has been etiologically linked to a novel coronavirus that has been named the SARS-associated coronavirus (SARS-CoV), whose genome was recently sequenced. Since it is a member of the Coronaviridae, its spike protein (S2) is believed to play a central role in viral entry by facilitating fusion between the viral and host cell membranes. The protein responsible for viral-induced membrane fusion of HIV-1 (gp41) differs in length, and has no sequence homology with S2. RESULTS: Sequence analysis reveals that the two viral proteins share the sequence motifs that construct their active conformation. These include (1) an N-terminal leucine/isoleucine zipper-like sequence, and (2) a C-terminal heptad repeat located upstream of (3) an aromatic residue-rich region juxtaposed to the (4) transmembrane segment. CONCLUSIONS: This study points to a similar mode of action for the two viral proteins, suggesting that anti-viral strategy that targets the viral-induced membrane fusion step can be adopted from HIV-1 to SARS-CoV. Recently the FDA approved Enfuvirtide, a synthetic peptide corresponding to the C-terminal heptad repeat of HIV-1 gp41, as an anti-AIDS agent. Enfuvirtide and C34, another anti HIV-1 peptide, exert their inhibitory activity by binding to a leucine/isoleucine zipper-like sequence in gp41, thus inhibiting a conformational change of gp41 required for its activation. We suggest that peptides corresponding to the C-terminal heptad repeat of the S2 protein may serve as inhibitors for SARS-CoV entry.",2003 Sep 21,"['Kliger, Yossef', 'Levanon, Erez Y']",BMC Microbiol,,,True
59ffca26c9d1f881e4e37e7c5af626d72d858dc4,PMC,Relationship of SARS-CoV to other pathogenic RNA viruses explored by tetranucleotide usage profiling,http://dx.doi.org/10.1186/1471-2105-4-43,PMC222961,14499005,NO-CC CODE,"BACKGROUND: The exact origin of the cause of the Severe Acute Respiratory Syndrome (SARS) is still an open question. The genomic sequence relationship of SARS-CoV with 30 different single-stranded RNA (ssRNA) viruses of various families was studied using two non-standard approaches. Both approaches began with the vectorial profiling of the tetra-nucleotide usage pattern V for each virus. In approach one, a distance measure of a vector V, based on correlation coefficient was devised to construct a relationship tree by the neighbor-joining algorithm. In approach two, a multivariate factor analysis was performed to derive the embedded tetra-nucleotide usage patterns. These patterns were subsequently used to classify the selected viruses. RESULTS: Both approaches yielded relationship outcomes that are consistent with the known virus classification. They also indicated that the genome of RNA viruses from the same family conform to a specific pattern of word usage. Based on the correlation of the overall tetra-nucleotide usage patterns, the Transmissible Gastroenteritis Virus (TGV) and the Feline CoronaVirus (FCoV) are closest to SARS-CoV. Surprisingly also, the RNA viruses that do not go through a DNA stage displayed a remarkable discrimination against the CpG and UpA di-nucleotide (z = -77.31, -52.48 respectively) and selection for UpG and CpA (z = 65.79,49.99 respectively). Potential factors influencing these biases are discussed. CONCLUSION: The study of genomic word usage is a powerful method to classify RNA viruses. The congruence of the relationship outcomes with the known classification indicates that there exist phylogenetic signals in the tetra-nucleotide usage patterns, that is most prominent in the replicase open reading frames.",2003 Sep 20,"['Yap, Yee Leng', 'Zhang, Xue Wu', 'Danchin, Antoine']",BMC Bioinformatics,,,True
e73a6a49cecb243ce24b57182cd354db7922d7e0,PMC,Diagnosis and treatment of severe sepsis,http://dx.doi.org/10.1186/cc6153,PMC2230613,18269689,NO-CC CODE,"The burden of infection in industrialized countries has prompted considerable effort to improve the outcomes of patients with sepsis. This has been formalized through the Surviving Sepsis Campaign 'bundles', derived from the recommendations of 11 professional societies, which have promoted global improvement in those practices whose primary goal it is to reduce sepsis-related death. However, difficulties remain in implementing all of the procedures recommended by the experts, despite the apparent pragmatism of those procedures. We summarize the main proposals made by the Surviving Sepsis Campaign and focus on the difficulties associated with making a proper diagnosis and supplying adequate treatment promptly to septic patients.",2007 Dec 19,"['Claessens, Yann-Erick', 'Dhainaut, Jean-François']",Crit Care,,,True
f41bba1e37e13b899c10c8f2c21b10fdc91930c2,PMC,Peptide Mimicrying Between SARS Coronavirus Spike Protein and Human Proteins Reacts with SARS Patient Serum,http://dx.doi.org/10.1155/2008/326464,PMC2254527,18320019,NO-CC CODE,"Molecular mimicry, defined as similar structures shared by molecules from dissimilar genes or proteins, is a general strategy used by pathogens to infect host cells. Severe acute respiratory syndrome (SARS) is a new human respiratory infectious disease caused by SARS coronavirus (SARS-CoV). The spike (S) protein of SARS-CoV plays an important role in the virus entry into a cell. In this study, eleven synthetic peptides from the S protein were selected based on its sequence homology with human proteins. Two of the peptides D07 (residues 927–937) and D08 (residues 942–951) were recognized by the sera of SARS patients. Murine hyperimmune sera against these peptides bound to proteins of human lung epithelial cells A549. Another peptide D10 (residues 490–502) stimulated A549 to proliferate and secrete IL-8. The present results suggest that the selected S protein regions, which share sequence homology with human proteins, may play important roles in SARS-CoV infection.",2008 Feb 19,"['Hwa, K.-Y.', 'Lin, W. M.', 'Hou, Y.-I.', 'Yeh, T.-M.']",J Biomed Biotechnol,,,True
149587a47192b3b0d086c8fa649c00ed2e3a4bcf,PMC,"Of epidemic proportions: physicians, personal risk, and public trust.",,PMC2259152,17132343,NO-CC CODE,,2005 Oct,"Clark, Chalmers C.",Yale J Biol Med,,,True
88e67b379a452f7aad18f4ed1746fceb0e301466,PMC,Talking to the public about a pandemic: some applications of the WHO outbreak communication guidelines.,,PMC2259158,17132344,NO-CC CODE,,2005 Oct,"Lanard, Jody",Yale J Biol Med,,,True
0a89f0c083b2766075f2e8f8cdfaeccf6c43e406,PMC,"Emerging diseases at the interface of people, domestic animals and wildlife. The role of wildlife in our understanding of highly pathogenic avian influenza.",,PMC2259160,17132341,NO-CC CODE,,2005 Oct,"Cook, Robert A.",Yale J Biol Med,,,True
f602e1eac50b0f5ad85c09bc5feb5b8c496cab51,PMC,Panglobalism and pandemics: ecological and ethical concerns.,,PMC2259162,17132337,NO-CC CODE,"A pandemic is a human medical problem but must be understood at multiple levels. Analysis of social and commercial forces is vital, and, more comprehensively, an ecological framework is necessary for an inclusive picture. Ecological health webworked with political and social determinants surrounds issues of human health. In this constellation of both natural and social factors, ethical concerns will arise at these multiple levels, from human health to the conservation and health of wild nature.",2005 Oct,"Rolston, Holmes",Yale J Biol Med,,,True
c6a34c64f00ecea47bb8b62a5e0c66dc173cd299,PMC,Enhancing the legitimacy of public health response in pandemic influenza planning: lessons from SARS.,,PMC2259163,17132340,NO-CC CODE,,2005 Oct,"Upshur, Ross E. G.",Yale J Biol Med,,,True
566b5c62fc77292ebe09295d59e7fbf6fc914260,PMC,Social Contacts and Mixing Patterns Relevant to the Spread of Infectious Diseases,http://dx.doi.org/10.1371/journal.pmed.0050074,PMC2270306,18366252,NO-CC CODE,"BACKGROUND: Mathematical modelling of infectious diseases transmitted by the respiratory or close-contact route (e.g., pandemic influenza) is increasingly being used to determine the impact of possible interventions. Although mixing patterns are known to be crucial determinants for model outcome, researchers often rely on a priori contact assumptions with little or no empirical basis. We conducted a population-based prospective survey of mixing patterns in eight European countries using a common paper-diary methodology. METHODS AND FINDINGS: 7,290 participants recorded characteristics of 97,904 contacts with different individuals during one day, including age, sex, location, duration, frequency, and occurrence of physical contact. We found that mixing patterns and contact characteristics were remarkably similar across different European countries. Contact patterns were highly assortative with age: schoolchildren and young adults in particular tended to mix with people of the same age. Contacts lasting at least one hour or occurring on a daily basis mostly involved physical contact, while short duration and infrequent contacts tended to be nonphysical. Contacts at home, school, or leisure were more likely to be physical than contacts at the workplace or while travelling. Preliminary modelling indicates that 5- to 19-year-olds are expected to suffer the highest incidence during the initial epidemic phase of an emerging infection transmitted through social contacts measured here when the population is completely susceptible. CONCLUSIONS: To our knowledge, our study provides the first large-scale quantitative approach to contact patterns relevant for infections transmitted by the respiratory or close-contact route, and the results should lead to improved parameterisation of mathematical models used to design control strategies.",2008 Mar 25,"['Mossong, Joël', 'Hens, Niel', 'Jit, Mark', 'Beutels, Philippe', 'Auranen, Kari', 'Mikolajczyk, Rafael', 'Massari, Marco', 'Salmaso, Stefania', 'Tomba, Gianpaolo Scalia', 'Wallinga, Jacco', 'Heijne, Janneke', 'Sadkowska-Todys, Malgorzata', 'Rosinska, Magdalena', 'Edmunds, W. John']",PLoS Med,,,True
57288607e089c162d64acbbcdf6bf6efcc454d44,PMC,Social Contacts and Mixing Patterns Relevant to the Spread of Infectious Diseases,http://dx.doi.org/10.1371/journal.pmed.0050074,PMC2270306,18366252,NO-CC CODE,"BACKGROUND: Mathematical modelling of infectious diseases transmitted by the respiratory or close-contact route (e.g., pandemic influenza) is increasingly being used to determine the impact of possible interventions. Although mixing patterns are known to be crucial determinants for model outcome, researchers often rely on a priori contact assumptions with little or no empirical basis. We conducted a population-based prospective survey of mixing patterns in eight European countries using a common paper-diary methodology. METHODS AND FINDINGS: 7,290 participants recorded characteristics of 97,904 contacts with different individuals during one day, including age, sex, location, duration, frequency, and occurrence of physical contact. We found that mixing patterns and contact characteristics were remarkably similar across different European countries. Contact patterns were highly assortative with age: schoolchildren and young adults in particular tended to mix with people of the same age. Contacts lasting at least one hour or occurring on a daily basis mostly involved physical contact, while short duration and infrequent contacts tended to be nonphysical. Contacts at home, school, or leisure were more likely to be physical than contacts at the workplace or while travelling. Preliminary modelling indicates that 5- to 19-year-olds are expected to suffer the highest incidence during the initial epidemic phase of an emerging infection transmitted through social contacts measured here when the population is completely susceptible. CONCLUSIONS: To our knowledge, our study provides the first large-scale quantitative approach to contact patterns relevant for infections transmitted by the respiratory or close-contact route, and the results should lead to improved parameterisation of mathematical models used to design control strategies.",2008 Mar 25,"['Mossong, Joël', 'Hens, Niel', 'Jit, Mark', 'Beutels, Philippe', 'Auranen, Kari', 'Mikolajczyk, Rafael', 'Massari, Marco', 'Salmaso, Stefania', 'Tomba, Gianpaolo Scalia', 'Wallinga, Jacco', 'Heijne, Janneke', 'Sadkowska-Todys, Malgorzata', 'Rosinska, Magdalena', 'Edmunds, W. John']",PLoS Med,,,False
6a42af8cbfae6626a1bfd9ef5c82c6526d743e15,PMC,Social Contacts and Mixing Patterns Relevant to the Spread of Infectious Diseases,http://dx.doi.org/10.1371/journal.pmed.0050074,PMC2270306,18366252,NO-CC CODE,"BACKGROUND: Mathematical modelling of infectious diseases transmitted by the respiratory or close-contact route (e.g., pandemic influenza) is increasingly being used to determine the impact of possible interventions. Although mixing patterns are known to be crucial determinants for model outcome, researchers often rely on a priori contact assumptions with little or no empirical basis. We conducted a population-based prospective survey of mixing patterns in eight European countries using a common paper-diary methodology. METHODS AND FINDINGS: 7,290 participants recorded characteristics of 97,904 contacts with different individuals during one day, including age, sex, location, duration, frequency, and occurrence of physical contact. We found that mixing patterns and contact characteristics were remarkably similar across different European countries. Contact patterns were highly assortative with age: schoolchildren and young adults in particular tended to mix with people of the same age. Contacts lasting at least one hour or occurring on a daily basis mostly involved physical contact, while short duration and infrequent contacts tended to be nonphysical. Contacts at home, school, or leisure were more likely to be physical than contacts at the workplace or while travelling. Preliminary modelling indicates that 5- to 19-year-olds are expected to suffer the highest incidence during the initial epidemic phase of an emerging infection transmitted through social contacts measured here when the population is completely susceptible. CONCLUSIONS: To our knowledge, our study provides the first large-scale quantitative approach to contact patterns relevant for infections transmitted by the respiratory or close-contact route, and the results should lead to improved parameterisation of mathematical models used to design control strategies.",2008 Mar 25,"['Mossong, Joël', 'Hens, Niel', 'Jit, Mark', 'Beutels, Philippe', 'Auranen, Kari', 'Mikolajczyk, Rafael', 'Massari, Marco', 'Salmaso, Stefania', 'Tomba, Gianpaolo Scalia', 'Wallinga, Jacco', 'Heijne, Janneke', 'Sadkowska-Todys, Malgorzata', 'Rosinska, Magdalena', 'Edmunds, W. John']",PLoS Med,,,False
dffbdd7bda7c2a404419c5a08fa5e3a363364d36,PMC,Social Contacts and Mixing Patterns Relevant to the Spread of Infectious Diseases,http://dx.doi.org/10.1371/journal.pmed.0050074,PMC2270306,18366252,NO-CC CODE,"BACKGROUND: Mathematical modelling of infectious diseases transmitted by the respiratory or close-contact route (e.g., pandemic influenza) is increasingly being used to determine the impact of possible interventions. Although mixing patterns are known to be crucial determinants for model outcome, researchers often rely on a priori contact assumptions with little or no empirical basis. We conducted a population-based prospective survey of mixing patterns in eight European countries using a common paper-diary methodology. METHODS AND FINDINGS: 7,290 participants recorded characteristics of 97,904 contacts with different individuals during one day, including age, sex, location, duration, frequency, and occurrence of physical contact. We found that mixing patterns and contact characteristics were remarkably similar across different European countries. Contact patterns were highly assortative with age: schoolchildren and young adults in particular tended to mix with people of the same age. Contacts lasting at least one hour or occurring on a daily basis mostly involved physical contact, while short duration and infrequent contacts tended to be nonphysical. Contacts at home, school, or leisure were more likely to be physical than contacts at the workplace or while travelling. Preliminary modelling indicates that 5- to 19-year-olds are expected to suffer the highest incidence during the initial epidemic phase of an emerging infection transmitted through social contacts measured here when the population is completely susceptible. CONCLUSIONS: To our knowledge, our study provides the first large-scale quantitative approach to contact patterns relevant for infections transmitted by the respiratory or close-contact route, and the results should lead to improved parameterisation of mathematical models used to design control strategies.",2008 Mar 25,"['Mossong, Joël', 'Hens, Niel', 'Jit, Mark', 'Beutels, Philippe', 'Auranen, Kari', 'Mikolajczyk, Rafael', 'Massari, Marco', 'Salmaso, Stefania', 'Tomba, Gianpaolo Scalia', 'Wallinga, Jacco', 'Heijne, Janneke', 'Sadkowska-Todys, Malgorzata', 'Rosinska, Magdalena', 'Edmunds, W. John']",PLoS Med,,,False
3c1616987b26e8e364fe129a42413c697772cdd8,PMC,Social Contacts and Mixing Patterns Relevant to the Spread of Infectious Diseases,http://dx.doi.org/10.1371/journal.pmed.0050074,PMC2270306,18366252,NO-CC CODE,"BACKGROUND: Mathematical modelling of infectious diseases transmitted by the respiratory or close-contact route (e.g., pandemic influenza) is increasingly being used to determine the impact of possible interventions. Although mixing patterns are known to be crucial determinants for model outcome, researchers often rely on a priori contact assumptions with little or no empirical basis. We conducted a population-based prospective survey of mixing patterns in eight European countries using a common paper-diary methodology. METHODS AND FINDINGS: 7,290 participants recorded characteristics of 97,904 contacts with different individuals during one day, including age, sex, location, duration, frequency, and occurrence of physical contact. We found that mixing patterns and contact characteristics were remarkably similar across different European countries. Contact patterns were highly assortative with age: schoolchildren and young adults in particular tended to mix with people of the same age. Contacts lasting at least one hour or occurring on a daily basis mostly involved physical contact, while short duration and infrequent contacts tended to be nonphysical. Contacts at home, school, or leisure were more likely to be physical than contacts at the workplace or while travelling. Preliminary modelling indicates that 5- to 19-year-olds are expected to suffer the highest incidence during the initial epidemic phase of an emerging infection transmitted through social contacts measured here when the population is completely susceptible. CONCLUSIONS: To our knowledge, our study provides the first large-scale quantitative approach to contact patterns relevant for infections transmitted by the respiratory or close-contact route, and the results should lead to improved parameterisation of mathematical models used to design control strategies.",2008 Mar 25,"['Mossong, Joël', 'Hens, Niel', 'Jit, Mark', 'Beutels, Philippe', 'Auranen, Kari', 'Mikolajczyk, Rafael', 'Massari, Marco', 'Salmaso, Stefania', 'Tomba, Gianpaolo Scalia', 'Wallinga, Jacco', 'Heijne, Janneke', 'Sadkowska-Todys, Malgorzata', 'Rosinska, Magdalena', 'Edmunds, W. John']",PLoS Med,,,False
4ba13c94e10bfebdd334f377f78e40bbf7e25d72,PMC,"Genetic susceptibility to infectious diseases: big is beautiful, but will bigger be even better?",http://dx.doi.org/10.1016/S1473-3099(06)70601-6,PMC2330096,17008174,NO-CC CODE,"Genetic epidemiology, including twin studies, provides robust evidence that genetic variation in human populations contributes to susceptibility to infectious disease. One of the major limitations of studies that attempt to identify the genes and mechanisms that underlie this susceptibility has been lack of power caused by small sample size. With the development of novel technologies, burgeoning information on the human genome, the HapMap project, and human genetic diversity, we are at the beginning of a new era in the study of the genetics of complex diseases. This review looks afresh at the epidemiological evidence that supports a role for genetics in susceptibility to infectious disease, examines the somewhat limited achievements to date, and discusses current advances in methodology and technology that will potentially lead to translational data in the future.",2006 Oct,"['Burgner, David', 'Jamieson, Sarra E', 'Blackwell, Jenefer M']",Lancet Infect Dis,,,False
085d7daf789f97c9886b9b8ab08bbf416d3128d2,PMC,"Genetic susceptibility to infectious diseases: big is beautiful, but will bigger be even better?",http://dx.doi.org/10.1016/S1473-3099(06)70601-6,PMC2330096,17008174,NO-CC CODE,"Genetic epidemiology, including twin studies, provides robust evidence that genetic variation in human populations contributes to susceptibility to infectious disease. One of the major limitations of studies that attempt to identify the genes and mechanisms that underlie this susceptibility has been lack of power caused by small sample size. With the development of novel technologies, burgeoning information on the human genome, the HapMap project, and human genetic diversity, we are at the beginning of a new era in the study of the genetics of complex diseases. This review looks afresh at the epidemiological evidence that supports a role for genetics in susceptibility to infectious disease, examines the somewhat limited achievements to date, and discusses current advances in methodology and technology that will potentially lead to translational data in the future.",2006 Oct,"['Burgner, David', 'Jamieson, Sarra E', 'Blackwell, Jenefer M']",Lancet Infect Dis,,,True
7f90265c6f254f3c10e47394f1a573a36507a7e5,PMC,"Genetic susceptibility to infectious diseases: big is beautiful, but will bigger be even better?",http://dx.doi.org/10.1016/S1473-3099(06)70601-6,PMC2330096,17008174,NO-CC CODE,"Genetic epidemiology, including twin studies, provides robust evidence that genetic variation in human populations contributes to susceptibility to infectious disease. One of the major limitations of studies that attempt to identify the genes and mechanisms that underlie this susceptibility has been lack of power caused by small sample size. With the development of novel technologies, burgeoning information on the human genome, the HapMap project, and human genetic diversity, we are at the beginning of a new era in the study of the genetics of complex diseases. This review looks afresh at the epidemiological evidence that supports a role for genetics in susceptibility to infectious disease, examines the somewhat limited achievements to date, and discusses current advances in methodology and technology that will potentially lead to translational data in the future.",2006 Oct,"['Burgner, David', 'Jamieson, Sarra E', 'Blackwell, Jenefer M']",Lancet Infect Dis,,,True
93adcbf3142015ef32b767777b0f4bfaba19a4bc,PMC,"Genetic susceptibility to infectious diseases: big is beautiful, but will bigger be even better?",http://dx.doi.org/10.1016/S1473-3099(06)70601-6,PMC2330096,17008174,NO-CC CODE,"Genetic epidemiology, including twin studies, provides robust evidence that genetic variation in human populations contributes to susceptibility to infectious disease. One of the major limitations of studies that attempt to identify the genes and mechanisms that underlie this susceptibility has been lack of power caused by small sample size. With the development of novel technologies, burgeoning information on the human genome, the HapMap project, and human genetic diversity, we are at the beginning of a new era in the study of the genetics of complex diseases. This review looks afresh at the epidemiological evidence that supports a role for genetics in susceptibility to infectious disease, examines the somewhat limited achievements to date, and discusses current advances in methodology and technology that will potentially lead to translational data in the future.",2006 Oct,"['Burgner, David', 'Jamieson, Sarra E', 'Blackwell, Jenefer M']",Lancet Infect Dis,,,True
4598e96f24115b1fd9bc0247cdd88e52beb5268f,PMC,CD13/Aminopeptidase N overexpression by basic fibroblast growth factor mediates enhanced invasiveness of 1F6 human melanoma cells,http://dx.doi.org/10.1038/sj.bjc.6603157,PMC2361307,16685268,NO-CC CODE,"CD13/Aminopeptidase N (CD13) is known to play an important role in tumour cell invasion. We examined whether basic fibroblast growth factor (bFGF) is involved in the regulation of CD13 expression in human melanoma cells. 1F6 human melanoma cells were stably transfected with constructs encoding either the 18 kDa (18kD) or all (ALL) bFGF isoform proteins. We observed highly increased CD13 mRNA and protein expression in the 1F6 clones regardless of the overexpression of either the 18kD or all isoform proteins. Neutral aminopeptidase activity was increased five-fold and could be inhibited by bestatin and the CD13-neutralising antibody WM15. The enhanced invasion through Matrigel, but not migration in a wound assay, was efficiently abrogated by both bestatin and WM15. Upregulation of CD13 expression was the result of increased epithelial and myeloid promoter activity up to 4.5-fold in 1F6-18kD and 1F6-ALL clones. Interestingly, in a panel of human melanoma cell lines, a significant correlation (r(2)=0.883, P<0.05) between bFGF and CD13 mRNA and protein expression was detected. High bFGF and CD13 expression were clearly related with an aggressive phenotype. Taken together, our data indicate that high bFGF expression upregulates CD13 expression in human melanoma cells by activating both the myeloid and the epithelial CD13 promoter. In addition, we show that high bFGF and CD13 expression results in enhanced invasive capacity and metastatic behaviour of human melanoma cells.",2006 Jun 5,"['Fontijn, D', 'Duyndam, M C A', 'van Berkel, M P A', 'Yuana, Y', 'Shapiro, L H', 'Pinedo, H M', 'Broxterman, H J', 'Boven, E']",Br J Cancer,,,True
2a1ca0c271e014530a0cd2ae77e3cb6457666133,PMC,Quantitative measurement of thyroglobulin mRNA in peripheral blood of patients after total thyroidectomy,http://dx.doi.org/10.1054/bjoc.2001.1904,PMC2363919,11437410,NO-CC CODE,"Previous studies have reported the clinical usefulness of reverse transcription-polymerase chain reaction (RT-PCR) detection of thyroglobulin (TG) mRNA in the peripheral blood of patients with differentiated thyroid carcinoma. To evaluate this usefulness, we measured TG mRNA in the peripheral blood of patients diagnosed with thyroid carcinoma after total thyroidectomy by real-time quantitative RT-PCR using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA as an internal control. Surprisingly, we detected TG mRNA in all samples obtained after total thyroidectomy, including those from 4 medullary carcinomas. Further, there was no statistical difference in expression levels of TG mRNA in the patients with or without metastasis, and no significant correlation was found between serum TG concentrations and the expression levels of TG mRNA. These results give rise to a question regarding the clinical applications of not only RT-PCR detection but also quantitative measurement of TG mRNA in peripheral blood. © 2001 Cancer Research Campaign http://www.bjcancer.com",2001 Jul,"['Takano, T', 'Miyauchi, A', 'Yoshida, H', 'Hasegawa, Y', 'Kuma, K', 'Amino, N']",Br J Cancer,,,True
763f208363aaabe89413dd846b11c9b37df4bd43,PMC,Early transcriptional response in the jejunum of germ-free piglets after oral infection with virulent rotavirus,http://dx.doi.org/10.1007/s00705-008-0118-6,PMC2441536,18523839,NO-CC CODE,"Germ-free piglets were orally infected with virulent rotavirus to collect jejunal mucosal scrapings at 12 and 18 hours post infection (two piglets per time point). IFN-gamma mRNA expression was stimulated in the mucosa of all four infected piglets, indicating that they all responded to the rotavirus infection. RNA pools prepared from two infected piglets were used to compare whole mucosal gene expression at 12 and 18 hpi to expression in uninfected germ-free piglets (n = 3) using a porcine intestinal cDNA microarray. Microarray analysis identified 13 down-regulated and 17 up-regulated genes. Northern blot analysis of a selected group of genes confirmed the data of the microarray. Genes were functionally clustered in interferon-regulated genes, proliferation/differentiation genes, apoptosis genes, cytoskeleton genes, signal transduction genes, and enterocyte digestive, absorptive, and transport genes. Down-regulation of the transport gene cluster reflected in part the loss of rotavirus-infected enterocytes from the villous tips. Data mining suggested that several genes were regulated in lower- or mid-villus immature enterocytes and goblet cells, probably to support repair of the damaged epithelial cell layer at the villous tips. Furthermore, up-regulation was observed for IFN-γ induced guanylate binding protein 2, a protein that effectively inhibited VSV and EMCV replication in vitro (Arch Virol 150:1213–1220, 2005). This protein may play a role in the small intestine’s innate defense against enteric viruses like rotavirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-008-0118-6) contains supplementary material, which is available to authorized users.",2008 Jul 4,"['Hulst, Marcel', 'Kerstens, Hinri', 'de Wit, Agnes', 'Smits, Mari', 'van der Meulen, Jan', 'Niewold, Theo']",Arch Virol,,,False
c60e9faaf8d025d3cf00b275de051fc9bc3b5bd4,PMC,Early transcriptional response in the jejunum of germ-free piglets after oral infection with virulent rotavirus,http://dx.doi.org/10.1007/s00705-008-0118-6,PMC2441536,18523839,NO-CC CODE,"Germ-free piglets were orally infected with virulent rotavirus to collect jejunal mucosal scrapings at 12 and 18 hours post infection (two piglets per time point). IFN-gamma mRNA expression was stimulated in the mucosa of all four infected piglets, indicating that they all responded to the rotavirus infection. RNA pools prepared from two infected piglets were used to compare whole mucosal gene expression at 12 and 18 hpi to expression in uninfected germ-free piglets (n = 3) using a porcine intestinal cDNA microarray. Microarray analysis identified 13 down-regulated and 17 up-regulated genes. Northern blot analysis of a selected group of genes confirmed the data of the microarray. Genes were functionally clustered in interferon-regulated genes, proliferation/differentiation genes, apoptosis genes, cytoskeleton genes, signal transduction genes, and enterocyte digestive, absorptive, and transport genes. Down-regulation of the transport gene cluster reflected in part the loss of rotavirus-infected enterocytes from the villous tips. Data mining suggested that several genes were regulated in lower- or mid-villus immature enterocytes and goblet cells, probably to support repair of the damaged epithelial cell layer at the villous tips. Furthermore, up-regulation was observed for IFN-γ induced guanylate binding protein 2, a protein that effectively inhibited VSV and EMCV replication in vitro (Arch Virol 150:1213–1220, 2005). This protein may play a role in the small intestine’s innate defense against enteric viruses like rotavirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-008-0118-6) contains supplementary material, which is available to authorized users.",2008 Jul 4,"['Hulst, Marcel', 'Kerstens, Hinri', 'de Wit, Agnes', 'Smits, Mari', 'van der Meulen, Jan', 'Niewold, Theo']",Arch Virol,,,True
e02f049fee95cabc6dbd1795a61117b73bc084ec,PMC,Surveillance Sans Frontières: Internet-Based Emerging Infectious Disease Intelligence and the HealthMap Project,http://dx.doi.org/10.1371/journal.pmed.0050151,PMC2443186,18613747,NO-CC CODE,"John Brownstein and colleagues discuss HealthMap, an automated real-time system that monitors and disseminates online information about emerging infectious diseases.",2008 Jul 8,"['Brownstein, John S', 'Freifeld, Clark C', 'Reis, Ben Y', 'Mandl, Kenneth D']",PLoS Med,,,True
42822532587ea4f62ac2b8df0502ac1db09a9552,PMC,Clinical review: Influenza pandemic – physicians and their obligations,http://dx.doi.org/10.1186/cc6918,PMC2481470,18598380,NO-CC CODE,"An influenza pandemic threatens to be the most lethal public health crisis to confront the world. Physicians will have critical roles in diagnosis, containment and treatment of influenza, and their commitment to treat despite increased personal risks is essential for a successful public health response. The obligations of the medical profession stem from the unique skills of its practitioners, who are able to provide more effective aid than the general public in a medical emergency. The free choice of profession and the societal contract from which doctors derive substantial benefits affirm this commitment. In hospitals, the duty will fall upon specialties that are most qualified to deal with an influenza pandemic, such as critical care, pulmonology, anesthesiology and emergency medicine. It is unrealistic to expect that this obligation to treat should be burdened with unlimited risks. Instead, risks should be minimized and justified against the effectiveness of interventions. Institutional and public cooperation in logistics, remuneration and psychological/legal support may help remove the barriers to the ability to treat. By stepping forward in duty during such a pandemic, physicians will be able to reaffirm the ethical center of the profession and lead the rest of the healthcare team in overcoming the medical crisis.",2008 Jun 24,"['Anantham, Devanand', 'McHugh, Wendy', ""O'Neill, Stephen"", 'Forrow, Lachlan']",Crit Care,,,True
db23b1ede65392b310b9152cf2999ec8f86ebd9b,PMC,Viral membrane fusion,http://dx.doi.org/10.1038/nsmb.1456,PMC2517140,18596815,NO-CC CODE,"Infection by viruses having lipid-bilayer envelopes proceeds through fusion of the viral membrane with a membrane of the target cell. Viral ‘fusion proteins’ facilitate this process. They vary greatly in structure, but all seem to have a common mechanism of action, in which a ligand-triggered, large-scale conformational change in the fusion protein is coupled to apposition and merger of the two bilayers. We describe three examples—the influenza virus hemagglutinin, the flavivirus E protein and the vesicular stomatitis virus G protein—in some detail, to illustrate the ways in which different structures have evolved to implement this common mechanism. Fusion inhibitors can be effective antiviral agents.",2008 Jul,"Harrison, Stephen C",Nat Struct Mol Biol,,,True
6c403549ba4284ba1d23902b3250e2ccb72096c3,PMC,Frontiers in the Convergence of Bioscience and Information Technology,http://dx.doi.org/10.1155/2008/728908,PMC2519141,18769494,NO-CC CODE,,2008 Aug 24,"Howard, Daniel",J Biomed Biotechnol,,,False
3f4fc78e53396ab0573664ed3ff5d665751861f6,PMC,Optimizing antibiotic selection in treating COPD exacerbations,,PMC2528209,18488427,NO-CC CODE,"Our understanding of the etiology, pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD) has increased substantially in the last decade. Several new lines of evidence demonstrate that bacterial isolation from sputum during acute exacerbation in many instances reflects a cause-effect relationship. Placebo-controlled antibiotic trials in exacerbations of COPD demonstrate significant clinical benefits of antibiotic treatment in moderate and severe episodes. However, in the multitude of antibiotic comparison trials, the choice of antibiotics does not appear to affect the clinical outcome, which can be explained by several methodological limitations of these trials. Recently, comparison trials with nontraditional end-points have shown differences among antibiotics in the treatment of exacerbations of COPD. Observational studies that have examined clinical outcome of exacerbations have repeatedly demonstrated certain clinical characteristics to be associated with treatment failure or early relapse. Optimal antibiotic selection for exacerbations has therefore incorporated quantifying the risk for a poor outcome of the exacerbation and choosing antibiotics differently for low risk and high risk patients, reserving the broader spectrum drugs for the high risk patients. Though improved outcomes in exacerbations with antibiotic choice based on such risk stratification has not yet been demonstrated in prospective controlled trials, this approach takes into account concerns of disease heterogeneity, antibiotic resistance and judicious antibiotic use in exacerbations.",2008 Mar,"['Siddiqi, Attiya', 'Sethi, Sanjay']",Int J Chron Obstruct Pulmon Dis,,,True
a2132636acb6782dd23b7e691b8f847ad6d883d0,PMC,Respiratory syncytial virus: an important cause of acute respiratory illness among young adults undergoing military training,http://dx.doi.org/10.1111/j.1750-2659.2007.00029.x,PMC2564797,18846262,NO-CC CODE,"Background  Military recruits receiving training are vulnerable to acute respiratory disease and a significant proportion of illness is caused by unidentified pathogens. While some countries use surveillance programmes to monitor such illness, few data exist for recruits of the British Armed Forces. Objectives  Through active surveillance of approximately 1000 Royal Navy trainees during 2001, we sought to describe and determine the aetiology of acute respiratory illness. Methods  Standard viral culture was used together with serology and a novel highly sensitive real‐time PCR and molecular beacon probe assay for respiratory syncytial virus (RSV) detection. Results  Among 54 Royal Navy recruits with respiratory symptoms adenovirus was identified in 35%, influenza viruses in 19% and RSV in 14%. All recruits were absent from training for almost a week, most of whom were confined to the sickbay. Conclusions  This study is the first to document adenovirus and RSV as important causes of acute respiratory illness among Royal Navy trainees. The study findings demonstrate the clinical significance and challenges of diagnosing RSV infection in young adults.",2007 Sep 10,"['O’Shea, Matthew K.', 'Pipkin, Christopher', 'Cane, Patricia A.', 'Gray, Gregory C.']",Influenza Other Respir Viruses,,,True
f9cd3dff30e7874eda1680c8aff01511184b821c,PMC,"Hemagglutinating Encephalomyelitis Coronavirus Infection in Pigs, Argentina",http://dx.doi.org/10.3201/eid1403.070825,PMC2570804,18325268,NO-CC CODE,"We describe an outbreak of vomiting, wasting, and encephalomyelitis syndrome in piglets in Argentina, caused by porcine hemagglutinating encephalomyelitis coronavirus (PHE-CoV) infection. Diagnosis was made by epidemiologic factors, pathologic features, immunohistochemistry, reverse transcription–PCR, and genomic sequencing. This study documents PHE-CoV infection in South America.",2008 Mar,"['Quiroga, Maria A.', 'Cappuccio, Javier', 'Piñeyro, Pablo', 'Basso, Walter', 'Moré, Gastón', 'Kienast, Mariana', 'Schonfeld, Sergio', 'Cáncer, José L.', 'Arauz, Sandra', 'Pintos, María E.', 'Nanni, Mariana', 'Machuca, Mariana', 'Hirano, Norio', 'Perfumo, Carlos J.']",Emerg Infect Dis,,,True
b60e2996ec59f48cb2376f9c791d7253d0f220cd,PMC,Screening Pneumonia Patients for Mimivirus,http://dx.doi.org/10.3201/eid1403.071027,PMC2570813,18325263,NO-CC CODE,"Acanthamoeba polyphaga mimivirus (APM), a virus of free-living amebae, has reportedly caused human respiratory disease. Using 2 newly developed real-time PCR assays, we screened 496 respiratory specimens from 9 pneumonia-patient populations for APM. This virus was not detected in any specimen, which suggests it is not a common respiratory pathogen.",2008 Mar,"['Dare, Ryan K.', 'Chittaganpitch, Malinee', 'Erdman, Dean D.']",Emerg Infect Dis,,,True
c67da0716b299594f705eaae2945f8d1c72b7927,PMC,Resource Allocation during an Influenza Pandemic,http://dx.doi.org/10.3201/eid1403.071275,PMC2570815,18325284,NO-CC CODE,Resource Allocation during an Influenza Pandemic,2008 Mar,"['Paranthaman, Karthikeyan', 'Conlon, Christopher P.', 'Parker, Claire', 'McCarthy, Noel']",Emerg Infect Dis,,,True
7716cb3ff9dd83dbbd2b5c85eb25b31436a1bd9c,PMC,"Increased Mortality Rate Associated with Chikungunya Epidemic, Ahmedabad, India",http://dx.doi.org/10.3201/eid1403.070720,PMC2570824,18325255,NO-CC CODE,"A total of 3,056 excess deaths epidemiologically linked to chikungunya occurred in 2006.",2008 Mar,"['Mavalankar, Dileep', 'Shastri, Priya', 'Bandyopadhyay, Tathagata', 'Parmar, Jeram', 'Ramani, Karaikurichi V.']",Emerg Infect Dis,,,True
deff02a187178ad474a1c556ff4f134d48300ce9,PMC,Hantavirus RNA in Saliva from Patients with Hemorrhagic Fever with Renal Syndrome,http://dx.doi.org/10.3201/eid1403.071242,PMC2570843,18325254,NO-CC CODE,"Hantaviruses cause 2 zoonotic diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome. Infection is usually initiated after inhalation of virus-contaminated rodent excreta. In addition to the zoonotic infection route, growing evidence suggests person-to-person transmission of Andes virus. For this reason, we studied whether saliva from HFRS patients contained hantavirus. During an outbreak in northern Sweden of nephropathia epidemica (NE), a milder form of hemorrhagic fever with renal syndrome, we collected saliva and plasma from 14 hospitalized NE patients with verified Puumala virus (PUUV) infection. PUUV RNA was detected in saliva from 10 patients (range 1,530–121,323 PUUV RNA copies/mL) by quantitative reverse transcription–PCR. The PUUV S-segment sequences from saliva and plasma of the same patients were identical. Our data show that hantavirus RNA could be detected in human saliva several days after onset of disease symptoms and raise the question whether interhuman transmission of hantavirus may occur through saliva.",2008 Mar,"['Pettersson, Lisa', 'Klingström, Jonas', 'Hardestam, Jonas', 'Lundkvist, Åke', 'Ahlm, Clas', 'Evander, Magnus']",Emerg Infect Dis,,,True
fe9f6f9d341b4949a8216e59c3bbbe4ddc3a7d5f,PMC,"Chikungunya Fever in Travelers Returning to Europe from the Indian Ocean Region, 2006",http://dx.doi.org/10.3201/eid1403.070906,PMC2570846,18325256,NO-CC CODE,"Chikungunya fever has spread through several Indian Ocean islands and India, including popular travel destinations. To compare usefulness of diagnostic tests and to understand reasons for the magnitude and severity of an outbreak, we used 3 diagnostic methods to test 720 samples from 680 patients returning to Europe from the Indian Ocean region in 2006. Chikungunya infection was confirmed for 24.4% patients in the first half of the year and for 9.9% in the second half. Reverse transcription–PCR was positive for all samples taken up to day 4 after symptom onset. Immunofluorescence detected immunoglobulin (Ig) M on day 1 and IgG on day 2 for some patients, and in all patients from day 5 onward. Soon after onset of symptoms, patients had IgG and IgM and high viral loads (some >10(9) copies/mL plasma). These data will help healthcare providers select diagnostic tests for returning travelers.",2008 Mar,"['Panning, Marcus', 'Grywna, Klaus', 'van Esbroeck, Marjan', 'Emmerich, Petra', 'Drosten, Christian']",Emerg Infect Dis,,,True
f4389cc1e3aa62a33af3c9df3744898cad8a2c07,PMC,Coronaviruses: Molecular and Cellular Biology,http://dx.doi.org/10.3201/eid1404.080016,PMC2570902,,NO-CC CODE,Coronaviruses: Molecular and Cellular Biology,2008 Apr,"Leibowitz, Julian L.",Emerg Infect Dis,,,False
85f5df7c9d677a28ffd8dbbc544d268b79bca556,PMC,"Control Measures Used during Lymphogranuloma Venereum Outbreak, Europe",http://dx.doi.org/10.3201/eid1404.061583,PMC2570903,18394274,NO-CC CODE,"To assess the response to the reemergence of lymphogranuloma venereum, we conducted a cross-sectional survey by administering a structured questionnaire to representatives from 26 European countries. Responses were received from 18 countries. The ability to respond quickly and the measures used for outbreak detection and control varied. Evidence-based criteria were not consistently used to develop recommendations. We did not develop criteria to determine the effectiveness of the recommendations. The degree of preparedness for an unexpected outbreak, as well as the ability of countries to respond quickly to alerts, varied, which indicates weaknesses in the ability to control an outbreak. More guidance is needed to implement and evaluate control measures used during international outbreaks.",2008 Apr,"['Timen, Aura', 'Hulscher, Marlies E.J.L.', 'Vos, Dieuwke', 'van de Laar, Marita J.W.', 'Fenton, Kevin A.', 'van Steenbergen, Jim E.', 'van der Meer, Jos W.M.', 'Grol, Richard P.T.M.']",Emerg Infect Dis,,,True
08a5baead4b645020cadeb031cd31220322b734c,PMC,"Detection and Prevalence Patterns of Group I Coronaviruses in Bats, Northern Germany",http://dx.doi.org/10.3201/eid1404.071439,PMC2570906,18400147,NO-CC CODE,"We tested 315 bats from 7 different bat species in northern Germany for coronaviruses by reverse transcription–PCR. The overall prevalence was 9.8%. There were 4 lineages of group I coronaviruses in association with 4 different species of verspertilionid bats (Myotis dasycneme, M. daubentonii, Pipistrellus nathusii, P. pygmaeus). The lineages formed a monophyletic clade of bat coronaviruses found in northern Germany. The clade of bat coronaviruses have a sister relationship with a clade of Chinese type I coronaviruses that were also associated with the Myotis genus (M. ricketti). Young age and ongoing lactation, but not sex or existing gravidity, correlated significantly with coronavirus detection. The virus is probably maintained on the population level by amplification and transmission in maternity colonies, rather than being maintained in individual bats.",2008 Apr,"['Gloza-Rausch, Florian', 'Ipsen, Anne', 'Seebens, Antje', 'Göttsche, Matthias', 'Panning, Marcus', 'Drexler, Jan Felix', 'Petersen, Nadine', 'Annan, Augustina', 'Grywna, Klaus', 'Müller, Marcel', 'Pfefferle, Susanne', 'Drosten, Christian']",Emerg Infect Dis,,,True
6186625c6f0eef08356ddb8245f000d6de2e0744,PMC,Travel Medicine: Tales Behind the Science,http://dx.doi.org/10.3201/eid1403.071595,PMC2570935,,NO-CC CODE,,2008 Apr,"Carroll, I. Dale",Emerg Infect Dis,,,False
28c3136f729fa6b60127262e63ee74613597a1e6,PMC,Pandemic influenza: are we prepared to face our obligations?,http://dx.doi.org/10.1186/cc6938,PMC2575555,18638362,NO-CC CODE,"After decades of low personal risk for contracting lethal diseases, physicians are suddenly facing the possibility of a substantial increase in occupational risk during an influenza pandemic. If they are not confronted before the onset of an influenza pandemic, feelings of unease and fear or ignorance about physicians' professional obligations could profoundly hinder individual physicians in fulfilling their professional duties. Such feelings could therefore undermine institutional and societal preparations. In their review published in Critical Care, Anantham and coworkers outline the ethical framework that forms the basis of the professional obligations of physicians who respond to health care emergencies, such as an influenza pandemic.",2008 Jul 15,"Ehrenstein, Boris P",Crit Care,,,True
d36eb475d88c70eea0f81e38a0aa0811f91b2dc3,PMC,Corticosteroids for community-acquired pneumonia: time to act!,http://dx.doi.org/10.1186/cc6940,PMC2575557,18638361,NO-CC CODE,The use of corticosteroids for the treatment of community-acquired pneumonia has been reported for almost 50 years. A recent systematic analysis of the relevant literature suggested that corticosteroids reduce the critical illness associated with community-acquired pneumonia. There is little doubt that a prolonged administration of a moderate dose of corticosteroids may alleviate the systemic inflammatory response and subsequent organ dysfunction in severe infection. Whether these favorable effects on morbidity may translate into better survival and quality of life needs to be addressed in additional adequately powered randomized controlled trials.,2008 Jul 14,"['Annane, Djillali', 'Meduri, G Umberto']",Crit Care,,,True
a3935942e50683102c5f4f15da7563931648e329,PMC,Bench-to-bedside review: Rare and common viral infections in the intensive care unit – linking pathophysiology to clinical presentation,http://dx.doi.org/10.1186/cc6917,PMC2575602,18671826,NO-CC CODE,"Viral infections are common causes of respiratory tract disease in the outpatient setting but much less common in the intensive care unit. However, a finite number of viral agents cause respiratory tract disease in the intensive care unit. Some viruses, such as influenza, respiratory syncytial virus (RSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV), are relatively common. Others, such as adenovirus, severe acute respiratory syndrome (SARS)-coronavirus, Hantavirus, and the viral hemorrhagic fevers (VHFs), are rare but have an immense public health impact. Recognizing these viral etiologies becomes paramount in treatment, infection control, and public health measures. Therefore, a basic understanding of the pathogenesis of viral entry, replication, and host response is important for clinical diagnosis and initiating therapeutic options. This review discusses the basic pathophysiology leading to clinical presentations in a few common and rare, but important, viruses found in the intensive care unit: influenza, RSV, SARS, VZV, adenovirus, CMV, VHF, and Hantavirus.",2008 Jul 17,"['Stollenwerk, Nicholas', 'Harper, Richart W', 'Sandrock, Christian E']",Crit Care,,,True
4b371efad68f1f604961744b82c69e625e8faef5,PMC,Electron microscopy for the rapid detection and identification of viruses from clinical specimens.,,PMC2589215,2672617,NO-CC CODE,"The advantages of using electron microscopy for rapid diagnosis of virus infection from clinical specimens, for identification of virus isolates with unusual properties, and for monitoring endogenous agents in cell cultures are illustrated by several actual cases that have occurred over the years. The importance of using morphological characteristics of viruses for initial identification is emphasized.",1989 Mar-Apr,"Fong, C. K.",Yale J Biol Med,,,True
c817b976b111658ac342f938c26c72c0bf1c6e61,PMC,An evolutionary change in diagnostic virology.,,PMC2589218,2672623,NO-CC CODE,"The earliest laboratory diagnoses of viral infections were made by microscopy just after the turn of the twentieth century. Animal and egg inoculation were the methods of choice until tissue culture and serology accelerated the field of diagnostic virology during the fifties and sixties. More rapid methods, including electron microscopy, immunoassays, and nucleic acid probes, are now available and influencing laboratory decisions and patient care. This review discusses changes in science and society which have influenced diagnostic virology and how the discipline has responded to these influences.",1989 Mar-Apr,"Chernesky, M. A.",Yale J Biol Med,,,True
eede431ba944ca208bf69d6c10e40dc7d52db655,PMC,The major histocompatibility complex: the value of extended haplotypes in the analysis of associated immune diseases and disorders.,,PMC2589374,2293506,NO-CC CODE,"Major histocompatibility complex antigens are critical to an animal's immune response. In most animals, the extreme polymorphism of MHC molecules complicates studies of the role of this complex in the immune response. In mice, however, MHC haplotype-homozygous inbred strains have been developed which are invaluable in the study of the immune system and the search for immune response genes. The human MHC bears many similarities to its murine equivalent with regard to antigen structure and polymorphism; furthermore, a number of combinations of specific MHC alleles between HLA-B and HLA-DR/DQ (extended haplotypes) are found in people more commonly than predicted by individual allele frequencies. Over 30 percent of Caucasian haplotypes are extended haplotypes, and over 55 percent of individuals have at least one extended haplotype. Examples of the same extended haplotype, even in unrelated individuals, should either all have or lack any gene within the MHC region. The value of considering extended haplotypes in searching for associations between the MHC and diseases, or immune response, is shown in three examples: congenital adrenal hyperplasia, hepatitis B immunization, and transfusion-associated graft-versus-host disease.",1990 Sep-Oct,"Kruskall, M. S.",Yale J Biol Med,,,True
f7f228117ed266bdd9f35510bec8011dfcef21a1,PMC,Causation and disease: effect of technology on postulates of causation.,,PMC2589507,1814063,NO-CC CODE,"This paper reviews the technical developments in microbiology that led to the discovery of new infectious agents and the effect of these discoveries on establishing proof of causation. In bacteriology, these advances included the light microscope, bacterial stains, bacterial cultures, and the methods used to isolate clones. In virology, they involved the use of filters to separate viruses from bacteria, the electron microscope, the use of laboratory animals, embryonated eggs, tissue cultures to identify or grow the agent, and the recent development of molecular techniques to detect the presence of antigen in tissues. In immunology, they were based on the discovery of antibodies and of the immune response.",1991 Sep-Oct,"Evans, A. S.",Yale J Biol Med,,,True
62fc5c722d09d38217a96f1fb4e6831a0255b25d,PMC,Medical reviews. Coronaviruses.,,PMC2595130,4617423,NO-CC CODE,,1974 Dec,"Monto, A. S.",Yale J Biol Med,,,True
a8c1928d0295a8f2f13a679f4536ceff03508bde,PMC,Virus morphology as an aid for rapid diagnosis.,,PMC2595834,6155006,NO-CC CODE,"Standard methods of virus diagnosis may take many days to complete. As antiviral drugs are being used with more effectiveness, it becomes more important to develop rapid diagnostic methods. It takes only a few minutes to prepare and examine a specimen for electron microscopy (EM), using the negative staining technique. Viruses in the specimen can readily be identified by their morphology. In order to be detected by EM there must be at least 10(7) virus particles per milliliter of sample. This concentration is frequently found in certain types of specimens. The sensitivity of EM is increased 100-fold if homologous antibody is used to aggregate the virus. Visualization of virus-antibody aggregates forms the basis for serotyping by immunoelectron microscopy (IEM).",1980 Jan-Feb,"Doane, F. W.",Yale J Biol Med,,,True
7aa5c87d322c83d77e3a4d1a3ae55b0bace68625,PMC,Viral immunodiagnosis.,,PMC2595836,6990636,NO-CC CODE,"This review discusses the commonly employed methods for viral immunodiagnosis, mentions unusual or novel procedures, and briefly refers to the use of monoclonal antibody.",1980 Jan-Feb,"Baumgarten, A.",Yale J Biol Med,,,True
20029dc39eb2b7cd0a8392445e6596f93933258a,PMC,Has the virus of multiple sclerosis been isolated?,,PMC2596456,7180025,NO-CC CODE,"There have been many attempts to isolate infectious agents from patients with multiple sclerosis (MS), and many viruses have been incriminated at one time or another over the past few decades. However, in every case further research has disproved the original claim. Thus, we cautiously report on the isolation of four antigenically related agents from the cerebrospinal fluid (CSF) of three patients with MS and one patient with amyotrophic lateral sclerosis. The patients yielding the isolates from their CSF possessed neutralizing antibodies to the virus in their blood, in contrast to several other virus-free patients with chronic central nervous system (CNS) diseases studied at the same time. The virus could not be isolated from 27 patients who were not suffering from chronic disease of the CNS. The agent has not yet been adequately characterized, but it deserves further attention because it seems to be a hitherto unknown virus, difficult to isolate and difficult to work with in the laboratory. Its isolation from the four patients mentioned above (and subsequently in several other MS patients) warrants further investigation of its potential role in MS and other progressive diseases of the CNS.",1982 May-Aug,"Melnick, J. L.",Yale J Biol Med,,,True
de697e14b572a44814a93dabd82210bde299bdc2,PMC,In Memoriam: Michael B. Gregg (1930–2008),http://dx.doi.org/10.3201/eid1409.080952,PMC2599917,18760025,NO-CC CODE,,2008 Sep,"Morens, David M.",Emerg Infect Dis,,,True
e61dc248ce523ab72ae25a6974c9e10cc1dcdea7,PMC,Integrated Approaches and Empirical Models for Investigation of Parasitic Diseases in Northern Wildlife,http://dx.doi.org/10.3201/eid1401.071119,PMC2600137,18258071,NO-CC CODE,"The North is a frontier for exploration of emerging infectious diseases and the large-scale drivers influencing distribution, host associations, and evolution of pathogens among persons, domestic animals, and wildlife. Leading into the International Polar Year 2007–2008, we outline approaches, protocols, and empirical models derived from a decade of integrated research on northern host–parasite systems. Investigations of emerging infectious diseases associated with parasites in northern wildlife involved a network of multidisciplinary collaborators and incorporated geographic surveys, archival collections, historical foundations for diversity, and laboratory and field studies exploring the interface for hosts, parasites, and the environment. In this system, emergence of parasitic disease was linked to geographic expansion, host switching, resurgence due to climate change, and newly recognized parasite species. Such integrative approaches serve as cornerstones for detection, prediction, and potential mitigation of emerging infectious diseases in wildlife and persons in the North and elsewhere under a changing global climate.",2008 Jan,"['Hoberg, Eric P.', 'Polley, Lydden', 'Jenkins, Emily J.', 'Kutz, Susan J.', 'Veitch, Alasdair M.', 'Elkin, Brett T.']",Emerg Infect Dis,,,True
82fb52d462dc847ed33ec87be35bd5c5065844aa,PMC,Cross-subtype Immunity against Avian Influenza in Persons Recently Vaccinated for Influenza,http://dx.doi.org/10.3201/eid1401.061283,PMC2600140,18258091,NO-CC CODE,"Avian influenza virus (H5N1) can be transmitted to humans, resulting in a severe or fatal disease. The aim of this study was to evaluate the immune cross-reactivity between human and avian influenza (H5N1) strains in healthy donors vaccinated for seasonal influenza A (H1N1)/(H3N2). A small frequency of CD4 T cells specific for subtype H5N1 was detected in several persons at baseline, and seasonal vaccine administration enhanced the frequency of such reactive CD4 T cells. We also observed that seasonal vaccination is able to raise neutralizing immunity against influenza (H5N1) in a large number of donors. No correlation between influenza-specific CD4 T cells and humoral responses was observed. N1 may possibly be a target for both cellular and humoral cross-type immunity, but additional experiments are needed to clarify this point. These findings highlight the possibility of boosting cross-type cellular and humoral immunity against highly pathogenic avian influenza A virus subtype H5N1 by seasonal influenza vaccination.",2008 Jan,"['Gioia, Cristiana', 'Castilletti, Concetta', 'Tempestilli, Massimo', 'Piacentini, Paola', 'Bordi, Licia', 'Chiappini, Roberta', 'Agrati, Chiara', 'Squarcione, Salvatore', 'Ippolito, Giuseppe', 'Puro, Vincenzo', 'Capobianchi, Maria R.', 'Poccia, Fabrizio']",Emerg Infect Dis,,,True
466db44b1f77af3237d04ac0313bd03c2b2e94bc,PMC,"International Circumpolar Surveillance, An Arctic Network for the Surveillance of Infectious Diseases",http://dx.doi.org/10.3201/eid1401.070717,PMC2600151,18258072,NO-CC CODE,"Peoples of the Arctic and sub-Arctic regions live in social and physical environments that differ substantially from those of their more southern-dwelling counterparts. The cold northern climate keeps people indoors, amplifying the effects of household crowding, smoking, and inadequate ventilation on person-to-person spread of infectious disease. The emergence of antimicrobial drug resistance among bacterial pathogens, the reemergence of tuberculosis, the entrance of HIV into Arctic communities, and the specter of pandemic influenza or the sudden emergence and introduction of new viral pathogens such as severe acute respiratory syndrome are of increasing concern to residents, governments, and public health authorities. The International Circumpolar Surveillance system is a network of hospital, public health agencies, and reference laboratories throughout the Arctic linked together to collect, compare, and share uniform laboratory and epidemiologic data on infectious diseases and assist in the formulation of prevention and control strategies.",2008 Jan,"['Parkinson, Alan J.', 'Bruce, Michael G.', 'Zulz, Tammy', None]",Emerg Infect Dis,,,True
d22dce4d19758350089a8bca54f25e5b602e58b7,PMC,"Influenza Virus Samples, International Law, and Global Health Diplomacy",http://dx.doi.org/10.3201/eid1401.070700,PMC2600156,18258086,NO-CC CODE,"Indonesia’s decision to withhold samples of avian influenza virus A (H5N1) from the World Health Organization for much of 2007 caused a crisis in global health. The World Health Assembly produced a resolution to try to address the crisis at its May 2007 meeting. I examine how the parties to this controversy used international law in framing and negotiating the dispute. Specifically, I analyze Indonesia’s use of the international legal principle of sovereignty and its appeal to rules on the protection of biological and genetic resources found in the Convention on Biological Diversity. In addition, I consider how the International Health Regulations 2005 applied to the controversy. The incident involving Indonesia’s actions with virus samples illustrates both the importance and the limitations of international law in global health diplomacy.",2008 Jan,"Fidler, David P.",Emerg Infect Dis,,,True
372fcfd74ff4f579704d40ec8fe524357534ef22,PMC,Pandemic Influenza and Pregnant Women,http://dx.doi.org/10.3201/eid1401.070667,PMC2600164,18258087,NO-CC CODE,"Planning for a future influenza pandemic should include considerations specific to pregnant women. First, pregnant women are at increased risk for influenza-associated illness and death. The effects on the fetus of maternal influenza infection, associated fever, and agents used for prophylaxis and treatment should be taken into account. Pregnant women might be reluctant to comply with public health recommendations during a pandemic because of concerns regarding effects of vaccines or medications on the fetus. Guidelines regarding nonpharmaceutical interventions (e.g., voluntary quarantine) also might present special challenges because of conflicting recommendations about routine prenatal care and delivery. Finally, healthcare facilities need to develop plans to minimize exposure of pregnant women to ill persons, while ensuring that women receive necessary care.",2008 Jan,"['Rasmussen, Sonja A.', 'Jamieson, Denise J.', 'Bresee, Joseph S.']",Emerg Infect Dis,,,True
58a0dfba31e0a2965443ca1edd463fc3daed5138,PMC,"The International Polar Year, 2007–2008, An Opportunity to Focus on Infectious Diseases in Arctic Regions",http://dx.doi.org/10.3201/eid1401.071405,PMC2600170,18258069,NO-CC CODE,,2008 Jan,"Parkinson, Alan J.",Emerg Infect Dis,,,True
731829483bf1acb462e1be27f8873725169e2e88,PMC,Encyclopedia of Infectious Diseases: Modern Methodologies,http://dx.doi.org/10.3201/eid1402.071411,PMC2600183,,NO-CC CODE,,2008 Feb,"Ostroff, Stephen M.",Emerg Infect Dis,,,True
e646b7a9960fc90325ceaf6bade3ab0bc2b237ef,PMC,Human Bocavirus Infections in Hospitalized Children and Adults,http://dx.doi.org/10.3201/eid1402.070851,PMC2600186,18258113,NO-CC CODE,"Studies have reported human bocavirus (HBoV) in children with respiratory tract infections (RTIs), but only occasionally in adults. We searched for HBoV DNA in nasopharyngeal aspirates (NPAs) from adults with exacerbations of chronic bronchitis or pneumonia, from children hospitalized for acute RTIs, and from asymptomatic children during the winter of 2002–2003 in Canada. HBoV was detected in NPAs of 1 (0.8%) of 126 symptomatic adults, 31 (13.8%) of 225 symptomatic children, and 43 (43%) of 100 asymptomatic children undergoing elective surgery. Another virus was detected in 22 (71%) of the 31 HBoV-positive NPAs from symptomatic children. Two clades of HBoV were identified. The pathogenic role of HBoV in RTIs is uncertain because it was frequently detected in symptomatic and asymptomatic children and was commonly found with other viruses in symptomatic children.",2008 Feb,"['Longtin, Jean', 'Bastien, Martine', 'Gilca, Rodica', 'Leblanc, Eric', 'de Serres, Gaston', 'Bergeron, Michel G.', 'Boivin, Guy']",Emerg Infect Dis,,,True
2da16887635db893ede660723a373467674a9884,PMC,"Emerging Infectious Diseases: Trends and Issues, 2nd Edition",http://dx.doi.org/10.3201/eid1402.071424,PMC2600208,,NO-CC CODE,,2008 Feb,"['Kramer, Laura D.', 'Kauffman, Elizabeth']",Emerg Infect Dis,,,True
bc05e373e5ba03d2dcd4a11a1f8c80eea4475dfe,PMC,Social Support and Response to AIDS and Severe Acute Respiratory Syndrome,http://dx.doi.org/10.3201/eid1405.071070,PMC2600224,18439373,NO-CC CODE,"Negative public reactions to emerging infectious diseases can adversely affect population health. We assessed whether social support was associated with knowledge of, worry about, and attitudes towards AIDS and severe acute respiratory syndrome. Our findings suggest that social support may be central to our understanding of public responses to emerging infectious diseases.",2008 May,"['Nandi, Arijit', 'Tracy, Melissa', 'Aiello, Allison', 'Des Jarlais, Don C.', 'Galea, Sandro']",Emerg Infect Dis,,,False
45d5977d22dcb1bc57c9cd4348f63c1cc19eaa84,PMC,Social Support and Response to AIDS and Severe Acute Respiratory Syndrome,http://dx.doi.org/10.3201/eid1405.071070,PMC2600224,18439373,NO-CC CODE,"Negative public reactions to emerging infectious diseases can adversely affect population health. We assessed whether social support was associated with knowledge of, worry about, and attitudes towards AIDS and severe acute respiratory syndrome. Our findings suggest that social support may be central to our understanding of public responses to emerging infectious diseases.",2008 May,"['Nandi, Arijit', 'Tracy, Melissa', 'Aiello, Allison', 'Des Jarlais, Don C.', 'Galea, Sandro']",Emerg Infect Dis,,,True
eae82da25e8df59f046a3c31405984543b53dc2e,PMC,Public Response to Community Mitigation Measures for Pandemic Influenza,http://dx.doi.org/10.3201/eid1405.071437,PMC2600239,18439361,NO-CC CODE,"We report the results of a national survey conducted to help public health officials understand the public’s response to community mitigation interventions for a severe outbreak of pandemic influenza. Survey results suggest that if community mitigation measures are instituted, most respondents would comply with recommendations but would be challenged to do so if their income or job were severely compromised. The results also indicate that community mitigation measures could cause problems for persons with lower incomes and for racial and ethnic minorities. Twenty-four percent of respondents said that they would not have anyone available to take care of them if they became sick with pandemic influenza. Given these results, planning and public engagement will be needed to encourage the public to be prepared.",2008 May,"['Blendon, Robert J.', 'Koonin, Lisa M.', 'Benson, John M.', 'Cetron, Martin S.', 'Pollard, William E.', 'Mitchell, Elizabeth W.', 'Weldon, Kathleen J.', 'Herrmann, Melissa J.']",Emerg Infect Dis,,,True
578def3a338542ea59f0251c8f5fa32acc37a83c,PMC,Public Response to Community Mitigation Measures for Pandemic Influenza,http://dx.doi.org/10.3201/eid1405.071437,PMC2600239,18439361,NO-CC CODE,"We report the results of a national survey conducted to help public health officials understand the public’s response to community mitigation interventions for a severe outbreak of pandemic influenza. Survey results suggest that if community mitigation measures are instituted, most respondents would comply with recommendations but would be challenged to do so if their income or job were severely compromised. The results also indicate that community mitigation measures could cause problems for persons with lower incomes and for racial and ethnic minorities. Twenty-four percent of respondents said that they would not have anyone available to take care of them if they became sick with pandemic influenza. Given these results, planning and public engagement will be needed to encourage the public to be prepared.",2008 May,"['Blendon, Robert J.', 'Koonin, Lisa M.', 'Benson, John M.', 'Cetron, Martin S.', 'Pollard, William E.', 'Mitchell, Elizabeth W.', 'Weldon, Kathleen J.', 'Herrmann, Melissa J.']",Emerg Infect Dis,,,True
f1446580f1091a33b07aad5ecbe7151c5895cafc,PMC,Pandemic Influenza Planning in the United States from a Health Disparities Perspective,http://dx.doi.org/10.3201/eid1405.071301,PMC2600245,18439350,NO-CC CODE,"We explored how different socioeconomic and racial/ethnic groups in the United States might fare in an influenza pandemic on the basis of social factors that shape exposure, vulnerability to influenza virus, and timeliness and adequacy of treatment. We discuss policies that might differentially affect social groups’ risk for illness or death. Our purpose is not to establish the precise magnitude of disparities likely to occur; rather, it is to call attention to avoidable disparities that can be expected in the absence of systematic attention to differential social risks in pandemic preparedness plans. Policy makers at the federal, state, and local levels should consider potential sources of socioeconomic and racial/ethnic disparities during a pandemic and formulate specific plans to minimize these disparities.",2008 May,"['Blumenshine, Philip', 'Reingold, Arthur', 'Egerter, Susan', 'Mockenhaupt, Robin', 'Braveman, Paula', 'Marks, James']",Emerg Infect Dis,,,True
d32e506b9bb4c99bc79e4231c0db5f2581bf8a17,PMC,Coronavirus Antibodies in Bat Biologists,http://dx.doi.org/10.3201/eid1406.070964,PMC2600275,18507931,NO-CC CODE,,2008 Jun,"['Stockman, Lauren J.', 'Haynes, Lia M.', 'Miao, Congrong', 'Harcourt, Jennifer L.', 'Rupprecht, Charles E.', 'Ksiazek, Thomas G.', 'Hyde, Terri B.', 'Fry, Alicia M.', 'Anderson, Larry J.']",Emerg Infect Dis,,,True
4a356ebe0d7578b2c9bd8e9bc844d204632019a7,PMC,Validation of Syndromic Surveillance for Respiratory Pathogen Activity,http://dx.doi.org/10.3201/eid1406.071467,PMC2600280,18507902,NO-CC CODE,"Syndromic surveillance is increasingly used to signal unusual illness events. To validate data-source selection, we retrospectively investigated the extent to which 6 respiratory syndromes (based on different medical registries) reflected respiratory pathogen activity. These syndromes showed higher levels in winter, which corresponded with higher laboratory counts of Streptococcus pneumoniae, respiratory syncytial virus, and influenza virus. Multiple linear regression models indicated that most syndrome variations (up to 86%) can be explained by counts of respiratory pathogens. Absenteeism and pharmacy syndromes might reflect nonrespiratory conditions as well. We also observed systematic syndrome elevations in the fall, which were unexplained by pathogen counts but likely reflected rhinovirus activity. Earliest syndrome elevations were observed in absenteeism data, followed by hospital data (+1 week), pharmacy/general practitioner consultations (+2 weeks), and deaths/laboratory submissions (test requests) (+3 weeks). We conclude that these syndromes can be used for respiratory syndromic surveillance, since they reflect patterns in respiratory pathogen activity.",2008 Jun,"['van den Wijngaard, Cees', 'van Asten, Liselotte', 'van Pelt, Wilfrid', 'Nagelkerke, Nico J.D.', 'Verheij, Robert', 'de Neeling, Albert J.', 'Dekkers, Arnold', 'van der Sande, Marianne A.B.', 'van Vliet, Hans', 'Koopmans, Marion P.G.']",Emerg Infect Dis,,,True
a047cce70b858a4adfc4ee2c3a46a11c32757e9b,PMC,Validation of Syndromic Surveillance for Respiratory Pathogen Activity,http://dx.doi.org/10.3201/eid1406.071467,PMC2600280,18507902,NO-CC CODE,"Syndromic surveillance is increasingly used to signal unusual illness events. To validate data-source selection, we retrospectively investigated the extent to which 6 respiratory syndromes (based on different medical registries) reflected respiratory pathogen activity. These syndromes showed higher levels in winter, which corresponded with higher laboratory counts of Streptococcus pneumoniae, respiratory syncytial virus, and influenza virus. Multiple linear regression models indicated that most syndrome variations (up to 86%) can be explained by counts of respiratory pathogens. Absenteeism and pharmacy syndromes might reflect nonrespiratory conditions as well. We also observed systematic syndrome elevations in the fall, which were unexplained by pathogen counts but likely reflected rhinovirus activity. Earliest syndrome elevations were observed in absenteeism data, followed by hospital data (+1 week), pharmacy/general practitioner consultations (+2 weeks), and deaths/laboratory submissions (test requests) (+3 weeks). We conclude that these syndromes can be used for respiratory syndromic surveillance, since they reflect patterns in respiratory pathogen activity.",2008 Jun,"['van den Wijngaard, Cees', 'van Asten, Liselotte', 'van Pelt, Wilfrid', 'Nagelkerke, Nico J.D.', 'Verheij, Robert', 'de Neeling, Albert J.', 'Dekkers, Arnold', 'van der Sande, Marianne A.B.', 'van Vliet, Hans', 'Koopmans, Marion P.G.']",Emerg Infect Dis,,,False
cccc6d4345633099ad5574b4bbe23727e0e5edd0,PMC,In Memoriam: Joshua Lederberg (1925–2008),http://dx.doi.org/10.3201/eid1406.080413,PMC2600297,18507922,NO-CC CODE,,2008 Jun,"['Hughes, James M.', 'Drotman, D. Peter']",Emerg Infect Dis,,,True
2e285596b823368b401a5df5b07b6bbedd9a444a,PMC,Conflict and Emerging Infectious Diseases,http://dx.doi.org/10.3201/eid1406.080027,PMC2600301,18507934,NO-CC CODE,,2008 Jun,"Kelly-Hope, Louise A.",Emerg Infect Dis,,,True
a6223e7c69d8d8404a4576a0a6968cbf010c426d,PMC,Global Distribution of Novel Rhinovirus Genotype,http://dx.doi.org/10.3201/eid1406.080271,PMC2600308,18507910,NO-CC CODE,"Global surveillance for a novel rhinovirus genotype indicated its association with community outbreaks and pediatric respiratory disease in Africa, Asia, Australia, Europe, and North America. Molecular dating indicates that these viruses have been circulating for at least 250 years.",2008 Jun,"['Briese, Thomas', 'Renwick, Neil', 'Venter, Marietjie', 'Jarman, Richard G.', 'Ghosh, Dhrubaa', 'Köndgen, Sophie', 'Shrestha, Sanjaya K.', 'Hoegh, A. Mette', 'Casas, Inmaculada', 'Adjogoua, Edgard Valerie', 'Akoua-Koffi, Chantal', 'Myint, Khin Saw', 'Williams, David T.', 'Chidlow, Glenys', 'van den Berg, Ria', 'Calvo, Cristina', 'Koch, Orienka', 'Palacios, Gustavo', 'Kapoor, Vishal', 'Villari, Joseph', 'Dominguez, Samuel R.', 'Holmes, Kathryn V.', 'Harnett, Gerry', 'Smith, David', 'Mackenzie, John S.', 'Ellerbrok, Heinz', 'Schweiger, Brunhilde', 'Schønning, Kristian', 'Chadha, Mandeep S.', 'Leendertz, Fabian H.', 'Mishra, A.C.', 'Gibbons, Robert V.', 'Holmes, Edward C.', 'Lipkin, W. Ian']",Emerg Infect Dis,,,True
bce0050667b80e7ff893094d6d7ff84a005d14e3,PMC,Virus Transfer from Personal Protective Equipment to Healthcare Employees’ Skin and Clothing,http://dx.doi.org/10.3201/eid1408.080085,PMC2600382,18680659,NO-CC CODE,We evaluated a personal protective equipment removal protocol designed to minimize wearer contamination with pathogens. Following this protocol often resulted in virus transfer to hands and clothing. An altered protocol or other measures are needed to prevent healthcare worker contamination.,2008 Aug,"['Casanova, Lisa', 'Alfano-Sobsey, Edie', 'Rutala, William A.', 'Weber, David J.', 'Sobsey, Mark']",Emerg Infect Dis,,,True
5c11738d4ea5152d1ff5853607c37db61abaff53,PMC,Pandemic Influenza and Excess Intensive-Care Workload,http://dx.doi.org/10.3201/eid1410.080440,PMC2609860,18826813,NO-CC CODE,"In the Netherlands a major part of preparedness planning for an epidemic or pandemic consists of maintaining essential public services, e.g., by the police, fire departments, army personnel, and healthcare workers. We provide estimates for peak demand for healthcare workers, factoring in healthcare worker absenteeism and using estimates from published epidemiologic models on the expected evolution of pandemic influenza in relation to the impact on peak surge capacity of healthcare facilities and intensive care units (ICUs). Using various published scenarios, we estimate their effect in increasing the availability of healthcare workers for duty during a pandemic. We show that even during the peak of the pandemic, all patients requiring hospital and ICU admission can be served, including those who have non–influenza-related conditions. For this rigorous task differentiation, clear hierarchical management, unambiguous communication, and discipline are essential and we recommend informing and training non-ICU healthcare workers for duties in the ICU.",2008 Oct,"['Nap, Raoul E.', 'Andriessen, Maarten P.H.M.', 'Meessen, Nico E.L.', 'dos Reis Miranda, Dinis', 'van der Werf, Tjip S.']",Emerg Infect Dis,,,False
f8bcf50f84ee1bcfe3dc59fc94d6692a636d6c46,PMC,Pandemic Influenza and Excess Intensive-Care Workload,http://dx.doi.org/10.3201/eid1410.080440,PMC2609860,18826813,NO-CC CODE,"In the Netherlands a major part of preparedness planning for an epidemic or pandemic consists of maintaining essential public services, e.g., by the police, fire departments, army personnel, and healthcare workers. We provide estimates for peak demand for healthcare workers, factoring in healthcare worker absenteeism and using estimates from published epidemiologic models on the expected evolution of pandemic influenza in relation to the impact on peak surge capacity of healthcare facilities and intensive care units (ICUs). Using various published scenarios, we estimate their effect in increasing the availability of healthcare workers for duty during a pandemic. We show that even during the peak of the pandemic, all patients requiring hospital and ICU admission can be served, including those who have non–influenza-related conditions. For this rigorous task differentiation, clear hierarchical management, unambiguous communication, and discipline are essential and we recommend informing and training non-ICU healthcare workers for duties in the ICU.",2008 Oct,"['Nap, Raoul E.', 'Andriessen, Maarten P.H.M.', 'Meessen, Nico E.L.', 'dos Reis Miranda, Dinis', 'van der Werf, Tjip S.']",Emerg Infect Dis,,,False
bfc30febb21caaeca4b083ee15c7b36f94d8b3b4,PMC,Pandemic Influenza and Excess Intensive-Care Workload,http://dx.doi.org/10.3201/eid1410.080440,PMC2609860,18826813,NO-CC CODE,"In the Netherlands a major part of preparedness planning for an epidemic or pandemic consists of maintaining essential public services, e.g., by the police, fire departments, army personnel, and healthcare workers. We provide estimates for peak demand for healthcare workers, factoring in healthcare worker absenteeism and using estimates from published epidemiologic models on the expected evolution of pandemic influenza in relation to the impact on peak surge capacity of healthcare facilities and intensive care units (ICUs). Using various published scenarios, we estimate their effect in increasing the availability of healthcare workers for duty during a pandemic. We show that even during the peak of the pandemic, all patients requiring hospital and ICU admission can be served, including those who have non–influenza-related conditions. For this rigorous task differentiation, clear hierarchical management, unambiguous communication, and discipline are essential and we recommend informing and training non-ICU healthcare workers for duties in the ICU.",2008 Oct,"['Nap, Raoul E.', 'Andriessen, Maarten P.H.M.', 'Meessen, Nico E.L.', 'dos Reis Miranda, Dinis', 'van der Werf, Tjip S.']",Emerg Infect Dis,,,True
13cc0633cce64b71718f50ff5276ff5181a8e4fd,PMC,Pandemic Influenza and Excess Intensive-Care Workload,http://dx.doi.org/10.3201/eid1410.080440,PMC2609860,18826813,NO-CC CODE,"In the Netherlands a major part of preparedness planning for an epidemic or pandemic consists of maintaining essential public services, e.g., by the police, fire departments, army personnel, and healthcare workers. We provide estimates for peak demand for healthcare workers, factoring in healthcare worker absenteeism and using estimates from published epidemiologic models on the expected evolution of pandemic influenza in relation to the impact on peak surge capacity of healthcare facilities and intensive care units (ICUs). Using various published scenarios, we estimate their effect in increasing the availability of healthcare workers for duty during a pandemic. We show that even during the peak of the pandemic, all patients requiring hospital and ICU admission can be served, including those who have non–influenza-related conditions. For this rigorous task differentiation, clear hierarchical management, unambiguous communication, and discipline are essential and we recommend informing and training non-ICU healthcare workers for duties in the ICU.",2008 Oct,"['Nap, Raoul E.', 'Andriessen, Maarten P.H.M.', 'Meessen, Nico E.L.', 'dos Reis Miranda, Dinis', 'van der Werf, Tjip S.']",Emerg Infect Dis,,,True
e304aff78d3aa505cac8ded07d448f1e12a668ea,PMC,Risky Trade: Infectious Disease in the Era of Global Trade,http://dx.doi.org/10.3201/eid1410.080835,PMC2609866,,NO-CC CODE,,2008 Oct,"Price-Smith, Andrew",Emerg Infect Dis,,,False
506316bb7b959a3afda9ab87ea7d12a3bd239cde,PMC,"Unexplained Deaths and Critical Illnesses of Suspected Infectious Cause, Taiwan, 2000–2005",http://dx.doi.org/10.3201/eid1410.061587,PMC2609874,18826839,NO-CC CODE,"We report 5 years’ surveillance data from the Taiwan Centers for Disease Control on unexplained deaths and critical illnesses suspected of being caused by infection. A total of 130 cases were reported; the incidence rate was 0.12 per 100,000 person-years; and infectious causes were identified for 81 cases (62%).",2008 Oct,"['Wang, Tsung-Hsi', 'Wei, Kuo-Chen', 'Jiang, Donald Dah-Shyong', 'Chiu, Chan-Hsian', 'Chang, Shan-Chwen', 'Wang, Jung-Der']",Emerg Infect Dis,,,False
6861186b7e7dd18bce1b605b8fe879bf4c341207,PMC,"Unexplained Deaths and Critical Illnesses of Suspected Infectious Cause, Taiwan, 2000–2005",http://dx.doi.org/10.3201/eid1410.061587,PMC2609874,18826839,NO-CC CODE,"We report 5 years’ surveillance data from the Taiwan Centers for Disease Control on unexplained deaths and critical illnesses suspected of being caused by infection. A total of 130 cases were reported; the incidence rate was 0.12 per 100,000 person-years; and infectious causes were identified for 81 cases (62%).",2008 Oct,"['Wang, Tsung-Hsi', 'Wei, Kuo-Chen', 'Jiang, Donald Dah-Shyong', 'Chiu, Chan-Hsian', 'Chang, Shan-Chwen', 'Wang, Jung-Der']",Emerg Infect Dis,,,True
3ed0c2cb0dd726b902f5470fd984ce7cc7d6c62f,PMC,Human Rhinovirus Group C Infection in Children with Lower Respiratory Tract Infection,http://dx.doi.org/10.3201/eid1410.080545,PMC2609892,18826844,NO-CC CODE,,2008 Oct,"['Xiang, Zichun', 'Gonzalez, Richard', 'Xie, Zhengde', 'Xiao, Yan', 'Chen, Lan', 'Li, Yongjun', 'Liu, Chunyan', 'Hu, Yinghui', 'Yao, Yuan', 'Qian, Suyun', 'Geng, Rong', 'Vernet, Guy', 'Paranhos-Baccalà, Gláucia', 'Shen, Kunling', 'Jin, Qi', 'Wang, Jianwei']",Emerg Infect Dis,,,True
7e5895cf23d87d2246903fc27c53130ab5b4d9e4,PMC,"Effects of School Closures, 2008 Winter Influenza Season, Hong Kong",http://dx.doi.org/10.3201/eid1410.080646,PMC2609897,18826841,NO-CC CODE,"In winter 2008, kindergartens and primary schools in Hong Kong were closed for 2 weeks after media coverage indicated that 3 children had died, apparently from influenza. We examined prospective influenza surveillance data before, during, and after the closure. We did not find a substantial effect on community transmission.",2008 Oct,"['Cowling, Benjamin J.', 'Lau, Eric H.Y.', 'Lam, Conrad L.H.', 'Cheng, Calvin K.Y.', 'Kovar, Jana', 'Chan, Kwok Hung', 'Peiris, J.S. Malik', 'Leung, Gabriel M.']",Emerg Infect Dis,,,True
1dc18baed79c3ae009d73d109a7aaec9f9195a2f,PMC,Cost effective strategies for completing the Interactome,http://dx.doi.org/10.1038/nmeth.1283,PMC2613168,19079254,NO-CC CODE,"Comprehensive protein interaction mapping projects are underway for many model species and humans. A key step in these projects is estimating the time, cost, and personnel required for obtaining an accurate and complete map. Here, we model the cost of interaction map completion across a spectrum of experimental designs. We show that current efforts may require up to 20 independent tests covering each protein pair to approach completion. We explore designs for reducing this cost substantially, including prioritization of protein pairs, probability thresholding, and interaction prediction. The best designs lower cost by four-fold overall and >100-fold in early stages of mapping. We demonstrate the best strategy in an ongoing project in Drosophila, in which we map 450 high-confidence interactions using 47 microtiter plates, versus thousands of plates expected using current designs. This study provides a framework for assessing the feasibility of interaction mapping projects and for future efforts to increase their efficiency.",2009 Jan 14,"['Schwartz, Ariel S.', 'Yu, Jingkai', 'Gardenour, Kyle R.', 'Finley, Russell L.', 'Ideker, Trey']",Nat Methods,,,True
fb6abbffcf23a7f85906627f2203c55e784cee09,PMC,Cost effective strategies for completing the Interactome,http://dx.doi.org/10.1038/nmeth.1283,PMC2613168,19079254,NO-CC CODE,"Comprehensive protein interaction mapping projects are underway for many model species and humans. A key step in these projects is estimating the time, cost, and personnel required for obtaining an accurate and complete map. Here, we model the cost of interaction map completion across a spectrum of experimental designs. We show that current efforts may require up to 20 independent tests covering each protein pair to approach completion. We explore designs for reducing this cost substantially, including prioritization of protein pairs, probability thresholding, and interaction prediction. The best designs lower cost by four-fold overall and >100-fold in early stages of mapping. We demonstrate the best strategy in an ongoing project in Drosophila, in which we map 450 high-confidence interactions using 47 microtiter plates, versus thousands of plates expected using current designs. This study provides a framework for assessing the feasibility of interaction mapping projects and for future efforts to increase their efficiency.",2009 Jan 14,"['Schwartz, Ariel S.', 'Yu, Jingkai', 'Gardenour, Kyle R.', 'Finley, Russell L.', 'Ideker, Trey']",Nat Methods,,,True
941a9a3f0138f7c01ff930023a4aa428a18170e1,PMC,Gene Chip for Viral Discovery,http://dx.doi.org/10.1371/journal.pbio.0000003,PMC261871,,NO-CC CODE,,2003 Nov 17,,PLoS Biol,,,True
45d747c81ca2c36c26e66349ff45abc6a43b612c,PMC,Norwalk-like calicivirus genes in farm animals.,,PMC2627973,10653567,NO-CC CODE,"Viruses closely related to Norwalk-like viruses (NLVs) were recently found in stored stool samples from two calves (United Kingdom and Germany) and four pigs (Japan), sparking discussions about the potential for zoonotic transmission. To investigate if NLVs are commonly present in farm animals, pooled stool samples from 100 pig farms, 48 chicken farms, 43 dairy cow herds, and 75 veal calf farms from the Netherlands were assayed by reverse transcription- polymerase chain reaction amplification, using primers specific for the detection of NLVs from humans. NLV RNA was detected in 33 (44%) of the specimens from veal calf farms and two (2%) specimens from pig farms. Our data show that NLV infections until recently thought to be restricted to humans occur often in calves and sometimes in pigs. While zoonotic transmission has not been proven, these findings suggest that calves and pigs may be reservoir hosts of NLVs.",2000 Jan-Feb,"['van Der Poel, W. H.', 'Vinjé, J.', 'van Der Heide, R.', 'Herrera, M. I.', 'Vivo, A.', 'Koopmans, M. P.']",Emerg Infect Dis,,,True
7718cbb91f57cc5e715277c2c6fda2f404573c1f,PMC,Role of macrolide therapy in chronic obstructive pulmonary disease,,PMC2629987,18990961,NO-CC CODE,"Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability worldwide. The Global Burden of Disease study has concluded that COPD will become the third leading cause of death worldwide by 2020, and will increase its ranking of disability-adjusted life years lost from 12th to 5th. Acute exacerbations of COPD (AECOPD) are associated with impaired quality of life and pulmonary function. More frequent or severe AECOPDs have been associated with especially markedly impaired quality of life and a greater longitudinal loss of pulmonary function. COPD and AECOPDs are characterized by an augmented inflammatory response. Macrolide antibiotics are macrocyclical lactones that provide adequate coverage for the most frequently identified pathogens in AECOPD and have been generally included in published guidelines for AECOPD management. In addition, they exert broad-ranging, immunomodulatory effects both in vitro and in vivo, as well as diverse actions that suppress microbial virulence factors. Macrolide antibiotics have been used to successfully treat a number of chronic, inflammatory lung disorders including diffuse panbronchiolitis, asthma, noncystic fibrosis associated bronchiectasis, and cystic fibrosis. Data in COPD patients have been limited and contradictory but the majority hint to a potential clinical and biological effect. Additional, prospective, controlled data are required to define any potential treatment effect, the nature of this effect, and the role of bronchiectasis, baseline colonization, and other cormorbidities.",2008 Sep,"['Martinez, Fernando J', 'Curtis, Jeffrey L', 'Albert, Richard']",Int J Chron Obstruct Pulmon Dis,,,True
6861259e73b53c482dea9ed97abad64f5c1c479a,PMC,Isolation of Novel Adenovirus from Fruit Bat (Pteropus dasymallus yayeyamae),http://dx.doi.org/10.3201/eid1402.070932,PMC2630045,18258142,NO-CC CODE,Isolation of Novel Adenovirus from Fruit Bat,2008 Feb,"['Maeda, Ken', 'Hondo, Eiichi', 'Terakawa, Junpei', 'Kiso, Yasuo', 'Nakaichi, Numekazu', 'Endoh, Daiji', 'Sakai, Kouji', 'Morikawa, Shigeru', 'Mizutani, Tetsuya']",Emerg Infect Dis,,,True
ac6642c9936e8c0291bba6f5b6e812c891d2b072,PMC,Novel Human Rhinoviruses and Exacerbation of Asthma in Children,http://dx.doi.org/10.3201/eid1411.080386,PMC2630738,18976575,NO-CC CODE,"To determine links between human rhinoviruses (HRV) and asthma, we used data from a case–control study, March 2003–February 2004, among children with asthma. Molecular characterization identified several likely new HRVs and showed that association with asthma exacerbations was largely driven by HRV-A and a phylogenetically distinct clade of 8 strains, genogroup C.",2008 Nov,"['Khetsuriani, Nino', 'Lu, Xiaoyan', 'Teague, W. Gerald', 'Kazerouni, Neely', 'Anderson, Larry J.', 'Erdman, Dean D.']",Emerg Infect Dis,,,True
7a8f5602e6965231fd63c55c95b2d1523c3f8091,PMC,Role of Human Polyomaviruses in Respiratory Tract Disease in Young Children,http://dx.doi.org/10.3201/eid1411.080394,PMC2630739,18976566,NO-CC CODE,KI virus was detected in respiratory secretions of 8/367 (2.2%) symptomatic and 0/96 asymptomatic children (p = 0.215). WU virus was detected in 26/367 (7.1%) symptomatic and 6/96 (6.3%) asymptomatic children (p = 1.00). These human polyomaviruses may not independently cause respiratory tract disease in young children.,2008 Nov,"['Wattier, Rachel L.', 'Vázquez, Marietta', 'Weibel, Carla', 'Shapiro, Eugene D.', 'Ferguson, David', 'Landry, Marie L.', 'Kahn, Jeffrey S.']",Emerg Infect Dis,,,True
0b746643e6aba929cdb7b709d0af00d39f09cb79,PMC,"Prevalence and Pathogenicity of WU and KI Polyomaviruses in Children, the Netherlands",http://dx.doi.org/10.3201/eid1411.080464,PMC2630742,18976572,NO-CC CODE,"A longitudinal study in 2004 and 2005 detected polyomaviruses WU and KI in 44% and 17% of children with and without respiratory symptoms, respectively, in the Netherlands. In some children both viruses were detected for long periods. In several symptomatic children no other respiratory pathogen was detected.",2008 Nov,"['van der Zalm, Marieke M.', 'Rossen, John W. A.', 'van Ewijk, Bart E.', 'Wilbrink, Berry', 'van Esch, Petra C.H.M.', 'Wolfs, Tom F.W.', 'van der Ent, Cornelis K.']",Emerg Infect Dis,,,True
0bef65699098fb63e5091c44004b59bcdb52858f,PMC,"Influenza Virus (H5N1) in Live Bird Markets and Food Markets, Thailand",http://dx.doi.org/10.3201/eid1411.080683,PMC2630752,18976558,NO-CC CODE,A surveillance program for influenza A viruses (H5N1) was conducted in live bird and food markets in central Thailand during July 2006–August 2007. Twelve subtype H5N1 viruses were isolated. The subtype H5N1 viruses circulating in the markets were genetically related to those that circulated in Thailand during 2004–2005.,2008 Nov,"['Amonsin, Alongkorn', 'Choatrakol, Chuensakon', 'Lapkuntod, Jiradej', 'Tantilertcharoen, Rachod', 'Thanawongnuwech, Roongroje', 'Suradhat, Sanipa', 'Suwannakarn, Kamol', 'Theamboonlers, Apiradee', 'Poovorawan, Yong']",Emerg Infect Dis,,,True
a43dc2a14f1a0ea6e5203a062f130693f5fd2a4d,PMC,Preventing infections in non-hospital settings: long-term care.,,PMC2631702,11294707,NO-CC CODE,"Infection concerns in long-term care facilities include endemic infections, outbreaks, and colonization and infection with antimicrobial-drug resistant microorganisms. Infection control programs are now used in most long-term care facilities, but their impact on infections has not been rigorously evaluated. Preventive strategies need to address the changing complexity of care in these facilities, e.g., the increased use of invasive devices. The anticipated increase in the elderly population in the next several decades makes prevention of infection in long-term care facilities a priority.",2001 Mar-Apr,"Nicolle, L. E.",Emerg Infect Dis,,,True
5f8af3ed94e16f3560c088fc4ca349fc663f4be3,PMC,Emerging health care-associated infections in the geriatric population.,,PMC2631705,11294721,NO-CC CODE,"The increasing number of persons >65 years of age form a special population at risk for nosocomial and other health care-associated infections. The vulnerability of this age group is related to impaired host defenses such as diminished cell-mediated immunity. Lifestyle considerations, e.g., travel and living arrangements, and residence in nursing homes, can further complicate the clinical picture. The magnitude and diversity of health care-associated infections in the aging population are generating new arenas for prevention and control efforts.",2001 Mar-Apr,"Strausbaugh, L. J.",Emerg Infect Dis,,,True
70cb54e32fbc19f5a34a37e75cc9e9d6afc6c2f2,PMC,Epidemiology and prevention of pediatric viral respiratory infections in health-care institutions.,,PMC2631706,11294717,NO-CC CODE,"Nosocomial viral respiratory infections cause considerable illness and death on pediatric wards. Common causes of these infections include respiratory syncytial virus and influenza. Although primarily a community pathogen, rhinovirus also occasionally results in hospitalization and serious sequelae. This article reviews effective infection control interventions for these three pathogens, as well as ongoing controversies.",2001 Mar-Apr,"Goldmann, D. A.",Emerg Infect Dis,,,True
3aa64273e4b7c80baee8fe40bbbe5339dfc87c3b,PMC,"Sentinel-based Surveillance of Coyotes to Detect Bovine Tuberculosis, Michigan",http://dx.doi.org/10.3201/eid1412.071181,PMC2634611,19046508,NO-CC CODE,"Bovine tuberculosis (TB) is endemic in white-tailed deer (Odocoileus virginianus) in the northeastern portion of Michigan’s Lower Peninsula. Bovine TB in deer and cattle has created immense financial consequences for the livestock industry and hunting public. Surveillance identified coyotes (Canis latrans) as potential bio-accumulators of Mycobacterium bovis, a finding that generated interest in their potential to serve as sentinels for monitoring disease risk. We sampled 175 coyotes in the bovine TB–endemic area. Fifty-eight tested positive, and infection prevalence by county ranged from 19% to 52% (statistical mean 33%, SE 0.07). By contrast, prevalence in deer (n = 3,817) was lower (i.e., 1.49%; Mann-Whitney U(4,4) = 14, p<0.001). By focusing on coyotes rather than deer, we sampled 97% fewer individuals and increased the likelihood of detecting M. bovis by 40%. As a result of reduced sampling intensity, sentinel coyote surveys have the potential to be practical indicators of M. bovis presence in wildlife and livestock.",2008 Dec,"['VerCauteren, Kurt C.', 'Atwood, Todd C.', 'DeLiberto, Thomas J.', 'Smith, Holly J.', 'Stevenson, Justin S.', 'Thomsen, Bruce V.', 'Gidlewski, Thomas', 'Payeur, Janet']",Emerg Infect Dis,,,True
058c4cce2921ae76cd2083a447e61b0768924a2c,PMC,"Antibodies to Nipah or Nipah-like Viruses in Bats, China",http://dx.doi.org/10.3201/eid1412.080359,PMC2634619,19046545,NO-CC CODE,,2008 Dec,"['Li, Yan', 'Wang, Jianmin', 'Hickey, Andrew C.', 'Zhang, Yunzhi', 'Li, Yuchun', 'Wu, Yi', 'Zhang, Huajun', 'Yuan, Junfa', 'Han, Zhenggang', 'McEachern, Jennifer', 'Broder, Christopher C.', 'Wang, Lin-Fa', 'Shi, Zhengli']",Emerg Infect Dis,,,False
ec69d4cf6cbbee8eab930f347ca9ad135db8ef28,PMC,"Antibodies to Nipah or Nipah-like Viruses in Bats, China",http://dx.doi.org/10.3201/eid1412.080359,PMC2634619,19046545,NO-CC CODE,,2008 Dec,"['Li, Yan', 'Wang, Jianmin', 'Hickey, Andrew C.', 'Zhang, Yunzhi', 'Li, Yuchun', 'Wu, Yi', 'Zhang, Huajun', 'Yuan, Junfa', 'Han, Zhenggang', 'McEachern, Jennifer', 'Broder, Christopher C.', 'Wang, Lin-Fa', 'Shi, Zhengli']",Emerg Infect Dis,,,True
f2caaa5a4a9ddb82c1324b28106e08b30ccc501d,PMC,Detection and Phylogenetic Analysis of Group 1 Coronaviruses in South American Bats,http://dx.doi.org/10.3201/eid1412.080642,PMC2634629,19046513,NO-CC CODE,Bat coronaviruses (Bt-CoVs) are thought to be the precursors of severe acute respiratory syndrome coronavirus. We detected Bt-CoVs in 2 bat species from Trinidad. Phylogenetic analysis of the RNA-dependent RNA polymerase gene and helicase confirmed them as group 1 coronaviruses.,2008 Dec,"['Carrington, Christine V.F.', 'Foster, Jerome E.', 'Zhu, Hua Chen', 'Zhang, Jin Xia', 'Smith, Gavin J.D.', 'Thompson, Nadin', 'Auguste, Albert J.', 'Ramkissoon, Vernie', 'Adesiyun, Abiodun A.', 'Guan, Yi']",Emerg Infect Dis,,,True
e366e0d17ab75efbaaeeb16705d551d50a0c188a,PMC,Extraction of Glycyrrhizic Acid and Glabridin from Licorice,,PMC2635700,19325770,NO-CC CODE,"The extraction and separation conditions of glycyrrhizic acid and glabridin from licorice were investigated. By changing the different extraction solvents, procedures, times and temperature, the optimum extraction condition was established: the used of ethanol/water (30:70, v/v) as an extraction solvent, and 60 min dipping time under 50°C. The extracts of licorice were separated and determined by reversed-phase high performance liquid chromatography with a methanol/water (70:30, v/v, containing 1% acetic acid) as the mobile phase. Under the optimum extraction condition, 2.39 mg/g of glycyrrhizic acid and 0.92 mg/g of glabridin were extracted from Chinese licorice and the recoveries were 89.7% and 72.5% respectively.",2008 Apr 16,"['Tian, Minglei', 'Yan, Hongyuan', 'Row, Kyung Ho']",Int J Mol Sci,,,True
39cfbf03d49e10e11570e18ae30e0a4dc1a63d7b,PMC,"Viral Etiology of Common Cold in Children, Finland",http://dx.doi.org/10.3201/eid1502.081468,PMC2657644,19193292,NO-CC CODE,,2009 Feb,"['Ruohola, Aino', 'Waris, Matti', 'Allander, Tobias', 'Ziegler, Thedi', 'Heikkinen, Terho', 'Ruuskanen, Olli']",Emerg Infect Dis,,,True
190a3e95092a129b94052ac128ce9b690350d9af,PMC,Virus-Specific Read-Through Codon Preference Affects Infectivity of Chimeric Cucumber Green Mottle Mosaic Viruses Displaying a Dengue Virus Epitope,http://dx.doi.org/10.1155/2009/781712,PMC2659398,19325913,NO-CC CODE,"A Cucumber green mottle mosaic virus (CGMMV) was used to present a truncated dengue virus type 2 envelope (E) protein binding region from amino acids 379 to 423 (EB4). The EB4 gene was inserted at the terminal end of the CGMMV coat protein (CP) open reading frame (ORF). Read-through sequences of TMV or CGMMV, CAA-UAG-CAA-UUA, or AAA-UAG-CAA-UUA were, respectively, inserted in between the CP and the EB4 genes. The chimeric clones, pRT, pRG, and pCG+FSRTRE, were transcribed into full-length capped recombinant CGMMV transcripts. Only constructs with the wild-type CGMMV read-through sequence yielded infectious viruses following infection of host plant, muskmelon (Cucumis melo) leaves. The ratio of modified to unmodified CP for the read-through expression clone developed was also found to be approximately 1:1, higher than what has been previously reported. It was also observed that infectivity was not affected by differences in pI between the chimera and its wild counterpart. Analysis of recombinant viruses after 21-days-postinculation (dpi) revealed that deletions occurred resulting in partial reversions of the viral population to near wild type and suggesting that this would be the limiting harvest period for obtaining true to type recombinants with this construct.",2009 Mar 22,"['Teoh, Pak-Guan', 'Ooi, Aik-Seng', 'AbuBakar, Sazaly', 'Othman, Rofina Yasmin']",J Biomed Biotechnol,,,True
6a68dadda9052b8be43679f6aca30887677ffabb,PMC,Enhanced Hygiene Measures and Norovirus Transmission during an Outbreak,http://dx.doi.org/10.3201/1501.080299,PMC2660689,19116045,NO-CC CODE,"Control of norovirus outbreaks relies on enhanced hygiene measures, such as handwashing, surface cleaning, using disposable paper towels, and using separate toilets for sick and well persons. However, little is known about their effectiveness in limiting further spread of norovirus infections. We analyzed norovirus outbreaks in 7 camps at an international scouting jamboree in the Netherlands during 2004. Implementation of hygiene measures coincided with an 84.8% (95% predictive interval 81.2%–86.6%) reduction in reproduction number. This reduction was unexpectedly large but still below the reduction needed to contain a norovirus outbreak. Even more stringent control measures are required to break the chain of transmission of norovirus.",2009 Jan,"['Heijne, Janneke C.M.', 'Teunis, Peter', 'Morroy, Gabriella', 'Wijkmans, Clementine', 'Oostveen, Sandy', 'Duizer, Erwin', 'Kretzschmar, Mirjam', 'Wallinga, Jacco']",Emerg Infect Dis,,,True
9cd3e3b494131726a57bf2d8e5aeb5bc56239dd0,PMC,Enhanced Hygiene Measures and Norovirus Transmission during an Outbreak,http://dx.doi.org/10.3201/1501.080299,PMC2660689,19116045,NO-CC CODE,"Control of norovirus outbreaks relies on enhanced hygiene measures, such as handwashing, surface cleaning, using disposable paper towels, and using separate toilets for sick and well persons. However, little is known about their effectiveness in limiting further spread of norovirus infections. We analyzed norovirus outbreaks in 7 camps at an international scouting jamboree in the Netherlands during 2004. Implementation of hygiene measures coincided with an 84.8% (95% predictive interval 81.2%–86.6%) reduction in reproduction number. This reduction was unexpectedly large but still below the reduction needed to contain a norovirus outbreak. Even more stringent control measures are required to break the chain of transmission of norovirus.",2009 Jan,"['Heijne, Janneke C.M.', 'Teunis, Peter', 'Morroy, Gabriella', 'Wijkmans, Clementine', 'Oostveen, Sandy', 'Duizer, Erwin', 'Kretzschmar, Mirjam', 'Wallinga, Jacco']",Emerg Infect Dis,,,True
6369253a8ac4a54ae6bb4e0f855f0c18467b943b,PMC,Enhanced Hygiene Measures and Norovirus Transmission during an Outbreak,http://dx.doi.org/10.3201/1501.080299,PMC2660689,19116045,NO-CC CODE,"Control of norovirus outbreaks relies on enhanced hygiene measures, such as handwashing, surface cleaning, using disposable paper towels, and using separate toilets for sick and well persons. However, little is known about their effectiveness in limiting further spread of norovirus infections. We analyzed norovirus outbreaks in 7 camps at an international scouting jamboree in the Netherlands during 2004. Implementation of hygiene measures coincided with an 84.8% (95% predictive interval 81.2%–86.6%) reduction in reproduction number. This reduction was unexpectedly large but still below the reduction needed to contain a norovirus outbreak. Even more stringent control measures are required to break the chain of transmission of norovirus.",2009 Jan,"['Heijne, Janneke C.M.', 'Teunis, Peter', 'Morroy, Gabriella', 'Wijkmans, Clementine', 'Oostveen, Sandy', 'Duizer, Erwin', 'Kretzschmar, Mirjam', 'Wallinga, Jacco']",Emerg Infect Dis,,,False
2edf14d68de169e1e3457fb5134cf5cac92b5afc,PMC,School Closure to Reduce Influenza Transmission,http://dx.doi.org/10.3201/eid1501.081289,PMC2660715,19116082,NO-CC CODE,,2009 Jan,"['Koonin, Lisa M.', 'Cetron, Martin S.']",Emerg Infect Dis,,,True
d5baf9d8cdb27590c3f85afb7d2ecdf579128be2,PMC,Polyomaviruses KI and WU in Immunocompromised Patients with Respiratory Disease,http://dx.doi.org/10.3201/1501.080758,PMC2662633,19116066,NO-CC CODE,"Polyomaviruses KI (KIPyV) and WU (WUPyV) were recently identified, mainly in respiratory specimens from children. Among 200 patients with respiratory disorders admitted to Saint Louis Hospital, Paris, France, KIPyV was detected in 8% and WUPyV in 1%. KIPyV was significantly more frequent among human stem cell transplant patients (17.8% vs. 5.1%; p = 0.01).",2009 Jan,"['Mourez, Thomas', 'Bergeron, Anne', 'Ribaud, Patricia', 'Scieux, Catherine', 'Peffault de Latour, Régis', 'Tazi, Abdellatif', 'Socié, Gérard', 'Simon, François', 'LeGoff, Jérôme']",Emerg Infect Dis,,,False
5caf6fa187000ae494d50b2ed2ab15911b7da3b6,PMC,Polyomaviruses KI and WU in Immunocompromised Patients with Respiratory Disease,http://dx.doi.org/10.3201/1501.080758,PMC2662633,19116066,NO-CC CODE,"Polyomaviruses KI (KIPyV) and WU (WUPyV) were recently identified, mainly in respiratory specimens from children. Among 200 patients with respiratory disorders admitted to Saint Louis Hospital, Paris, France, KIPyV was detected in 8% and WUPyV in 1%. KIPyV was significantly more frequent among human stem cell transplant patients (17.8% vs. 5.1%; p = 0.01).",2009 Jan,"['Mourez, Thomas', 'Bergeron, Anne', 'Ribaud, Patricia', 'Scieux, Catherine', 'Peffault de Latour, Régis', 'Tazi, Abdellatif', 'Socié, Gérard', 'Simon, François', 'LeGoff, Jérôme']",Emerg Infect Dis,,,True
8a244626a996d30b62a52bb8705b889e74f3a5cf,PMC,Face Mask Use and Control of Respiratory Virus Transmission in Households,http://dx.doi.org/10.3201/eid1502.081167,PMC2662657,19193267,NO-CC CODE,"Many countries are stockpiling face masks for use as a nonpharmaceutical intervention to control virus transmission during an influenza pandemic. We conducted a prospective cluster-randomized trial comparing surgical masks, non–fit-tested P2 masks, and no masks in prevention of influenza-like illness (ILI) in households. Mask use adherence was self-reported. During the 2006 and 2007 winter seasons, 286 exposed adults from 143 households who had been exposed to a child with clinical respiratory illness were recruited. We found that adherence to mask use significantly reduced the risk for ILI-associated infection, but <50% of participants wore masks most of the time. We concluded that household use of face masks is associated with low adherence and is ineffective for controlling seasonal respiratory disease. However, during a severe pandemic when use of face masks might be greater, pandemic transmission in households could be reduced. Many countries are stockpiling face masks for use as nonpharmaceutical interventions to reduce viral transmission during an influenza pandemic. We conducted a prospective cluster-randomized trial comparing surgical masks, non–fit-tested P2 masks, and no masks in prevention of influenza-like illness (ILI) in households. During the 2006 and 2007 winter seasons, 286 exposed adults from 143 households who had been exposed to a child with clinical respiratory illness were recruited. Intent-to-treat analysis showed no significant difference in the relative risk of ILI in the mask use groups compared with the control group; however, <50% of those in the mask use groups reported wearing masks most of the time. Adherence to mask use was associated with a significantly reduced risk of ILI-associated infection. We concluded that household use of masks is associated with low adherence and is ineffective in controlling seasonal ILI. If adherence were greater, mask use might reduce transmission during a severe influenza pandemic.",2009 Feb,"['MacIntyre, C. Raina', 'Cauchemez, Simon', 'Dwyer, Dominic E.', 'Seale, Holly', 'Cheung, Pamela', 'Browne, Gary', 'Fasher, Michael', 'Wood, James', 'Gao, Zhanhai', 'Booy, Robert', 'Ferguson, Neil']",Emerg Infect Dis,,,True
6cabfa322c9c7ae5d082357948957b303baacba8,PMC,Face Mask Use and Control of Respiratory Virus Transmission in Households,http://dx.doi.org/10.3201/eid1502.081167,PMC2662657,19193267,NO-CC CODE,"Many countries are stockpiling face masks for use as a nonpharmaceutical intervention to control virus transmission during an influenza pandemic. We conducted a prospective cluster-randomized trial comparing surgical masks, non–fit-tested P2 masks, and no masks in prevention of influenza-like illness (ILI) in households. Mask use adherence was self-reported. During the 2006 and 2007 winter seasons, 286 exposed adults from 143 households who had been exposed to a child with clinical respiratory illness were recruited. We found that adherence to mask use significantly reduced the risk for ILI-associated infection, but <50% of participants wore masks most of the time. We concluded that household use of face masks is associated with low adherence and is ineffective for controlling seasonal respiratory disease. However, during a severe pandemic when use of face masks might be greater, pandemic transmission in households could be reduced. Many countries are stockpiling face masks for use as nonpharmaceutical interventions to reduce viral transmission during an influenza pandemic. We conducted a prospective cluster-randomized trial comparing surgical masks, non–fit-tested P2 masks, and no masks in prevention of influenza-like illness (ILI) in households. During the 2006 and 2007 winter seasons, 286 exposed adults from 143 households who had been exposed to a child with clinical respiratory illness were recruited. Intent-to-treat analysis showed no significant difference in the relative risk of ILI in the mask use groups compared with the control group; however, <50% of those in the mask use groups reported wearing masks most of the time. Adherence to mask use was associated with a significantly reduced risk of ILI-associated infection. We concluded that household use of masks is associated with low adherence and is ineffective in controlling seasonal ILI. If adherence were greater, mask use might reduce transmission during a severe influenza pandemic.",2009 Feb,"['MacIntyre, C. Raina', 'Cauchemez, Simon', 'Dwyer, Dominic E.', 'Seale, Holly', 'Cheung, Pamela', 'Browne, Gary', 'Fasher, Michael', 'Wood, James', 'Gao, Zhanhai', 'Booy, Robert', 'Ferguson, Neil']",Emerg Infect Dis,,,False
0ae70ae84cc9052dedf214ca44a842f0f9edc161,PMC,Capacity of Thailand to Contain an Emerging Influenza Pandemic,http://dx.doi.org/10.3201/eid1503.080872,PMC2666290,19239756,NO-CC CODE,"Southeast Asia will likely be the epicenter of the next influenza pandemic. To determine whether health system resources in Thailand are sufficient to contain an emerging pandemic, we mapped health system resources in 76 provinces. We used 3 prepandemic scenarios of clustered cases and determined resource needs, availability, and gaps. We extended this analysis to a scenario of a modest pandemic and assumed that the same standards of clinical care would be required. We found that gaps exist in many resource categories, even under scenarios in which few cases occur. Such gaps are likely to be profound if a severe pandemic occurs. These gaps exist in infrastructure, personnel and materials, and surveillance capacity. Policy makers must determine whether such resource gaps can realistically be closed, ideally before a pandemic occurs. Alternatively, explicit assumptions must be made regarding allocation of scarce resources, standards of care, and priority setting during a pandemic.",2009 Mar,"['Putthasri, Weerasak', 'Lertiendumrong, Jongkol', 'Chompook, Pornthip', 'Tangcharoensathien, Viroj', 'Coker, Richard']",Emerg Infect Dis,,,True
aea62023f49b491e3f81fb977576ef64b5821342,PMC,Capacity of Thailand to Contain an Emerging Influenza Pandemic,http://dx.doi.org/10.3201/eid1503.080872,PMC2666290,19239756,NO-CC CODE,"Southeast Asia will likely be the epicenter of the next influenza pandemic. To determine whether health system resources in Thailand are sufficient to contain an emerging pandemic, we mapped health system resources in 76 provinces. We used 3 prepandemic scenarios of clustered cases and determined resource needs, availability, and gaps. We extended this analysis to a scenario of a modest pandemic and assumed that the same standards of clinical care would be required. We found that gaps exist in many resource categories, even under scenarios in which few cases occur. Such gaps are likely to be profound if a severe pandemic occurs. These gaps exist in infrastructure, personnel and materials, and surveillance capacity. Policy makers must determine whether such resource gaps can realistically be closed, ideally before a pandemic occurs. Alternatively, explicit assumptions must be made regarding allocation of scarce resources, standards of care, and priority setting during a pandemic.",2009 Mar,"['Putthasri, Weerasak', 'Lertiendumrong, Jongkol', 'Chompook, Pornthip', 'Tangcharoensathien, Viroj', 'Coker, Richard']",Emerg Infect Dis,,,False
c9610eb83659d81169046e71d9312d73ea8377e5,PMC,International Course on Emerging Viruses in the Amazon Region,http://dx.doi.org/10.3201/eid1504.080367,PMC2671423,19331725,NO-CC CODE,,2009 Apr,"['do Vale Gomes, Ana Lisa', 'Magalhães, Cintia', 'Melo, Fernando', 'Inga, Rocio', 'Gadelha, Sandra R.']",Emerg Infect Dis,,,False
2735c2e5b493fd4e7b7c4ec3d44a775f9399aa0d,PMC,Enhancing Time-Series Detection Algorithms for Automated Biosurveillance,http://dx.doi.org/10.3201/1504.080616,PMC2671446,19331728,NO-CC CODE,"BioSense is a US national system that uses data from health information systems for automated disease surveillance. We studied 4 time-series algorithm modifications designed to improve sensitivity for detecting artificially added data. To test these modified algorithms, we used reports of daily syndrome visits from 308 Department of Defense (DoD) facilities and 340 hospital emergency departments (EDs). At a constant alert rate of 1%, sensitivity was improved for both datasets by using a minimum standard deviation (SD) of 1.0, a 14–28 day baseline duration for calculating mean and SD, and an adjustment for total clinic visits as a surrogate denominator. Stratifying baseline days into weekdays versus weekends to account for day-of-week effects increased sensitivity for the DoD data but not for the ED data. These enhanced methods may increase sensitivity without increasing the alert rate and may improve the ability to detect outbreaks by using automated surveillance system data.",2009 Apr,"['Tokars, Jerome I.', 'Burkom, Howard', 'Xing, Jian', 'English, Roseanne', 'Bloom, Steven', 'Cox, Kenneth', 'Pavlin, Julie A.']",Emerg Infect Dis,,,True
07fe504a3b64db4dd23da77929893eb89215f3be,PMC,Frequency and clinical relevance of human bocavirus infection in acute exacerbations of chronic obstructive pulmonary disease,,PMC2672801,19436697,NO-CC CODE,"OBJECTIVE: Human bocavirus (HBoV) is a recently discovered parvovirus associated with acute respiratory tract infections in children. The objective of the present study was to determine the frequency and clinical relevance of HBoV infection in adult patients with acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). METHODS: We retrospectively tested 212 COPD patients, 141 (66.5%) with AE-COPD and 71 (33.5%) with stable disease, of whom nasal lavage and induced sputum had been obtained for the presence of HBoV deoxyribonucleic acid (DNA). The specificity of positive polymerase chain reaction results was confirmed by sequencing. RESULTS: Two hundred two of 212 patients for whom PCR results were available both for nasal lavage and induced sputum samples were eligible for data analysis. HBoV DNA was detected in three patients (1.5%). Of those, only one patient had AE-COPD. Thus, the frequency of HBoV infection demonstrated to be low in both AE-COPD (0.8%) and stable COPD (2.9%). HBoV was found in two sputum and one nasal lavage sample in different patients, respectively. Sequencing revealed >99% sequence identity with the reference strain. CONCLUSION: HBoV detection was infrequent. Since we detected HBoV in both upper and lower respiratory tract specimens and in AE-COPD as well as stable disease, a major role of HBoV infection in adults with AE-COPD is unlikely.",2009 Apr 15,"['Ringshausen, Felix C', 'Tan, Ai-Yui M', 'Allander, Tobias', 'Borg, Irmgard', 'Arinir, Umut', 'Kronsbein, Juliane', 'Hauptmeier, Barbara M', 'Schultze-Werninghaus, Gerhard', 'Rohde, Gernot']",Int J Chron Obstruct Pulmon Dis,,,True
faa9aae68713e08818d4eaeb3a3f8c02f075d21b,PMC,Meeting the Challenge of Influenza Pandemic Preparedness in Developing Countries,http://dx.doi.org/10.3201/eid1503.080857,PMC2681116,19239746,NO-CC CODE,"Developing countries face unique difficulties preparing for an influenza pandemic. Our current top-down approach will not provide these countries with adequate supplies of vaccines and antiviral agents. Consequently, they will have to use a bottom-up approach based on inexpensive generic agents that either modify the host response to influenza virus or act as antiviral agents. Several of these agents have shown promise, and many are currently produced in developing countries. Investigators must primarily identify agents for managing infection in populations and not simply seek explanations for how they work. They must determine in which countries these agents are produced and define patterns of distribution and costs. Because prepandemic research cannot establish whether these agents will be effective in a pandemic, randomized controlled trials must begin immediately after a new pandemic virus has emerged. Without this research, industrialized and developing countries could face an unprecedented health crisis.",2009 Mar,"Fedson, David S.",Emerg Infect Dis,,,True
6a98c9b230674dbe10a4e42f93436b229966ae46,PMC,Detection of Novel SARS-like and Other Coronaviruses in Bats from Kenya,http://dx.doi.org/10.3201/eid1503.081013,PMC2681120,19239771,NO-CC CODE,"Diverse coronaviruses have been identified in bats from several continents but not from Africa. We identified group 1 and 2 coronaviruses in bats in Kenya, including SARS-related coronaviruses. The sequence diversity suggests that bats are well-established reservoirs for and likely sources of coronaviruses for many species, including humans.",2009 Mar,"['Tong, Suxiang', 'Conrardy, Christina', 'Ruone, Susan', 'Kuzmin, Ivan V.', 'Guo, Xiling', 'Tao, Ying', 'Niezgoda, Michael', 'Haynes, Lia', 'Agwanda, Bernard', 'Breiman, Robert F.', 'Anderson, Larry J.', 'Rupprecht, Charles E.']",Emerg Infect Dis,,,True
ec1ffddf6d1cb1f2a96a599bf0d2b3c70d5dec58,PMC,Merkel Cell Polyomavirus DNA in Respiratory Specimens from Children and Adults,http://dx.doi.org/10.3201/eid1503.081067,PMC2681122,19239774,NO-CC CODE,Merkel cell polyomavirus (MCPyV) DNA was detected in 7 (1.3%) of 526 respiratory tract samples from patients in Australia with upper or lower respiratory tract symptoms. Partial T antigen and major capsid protein sequences of MCPyV identified in respiratory secretions showed high homology (99%–100%) to those found in Merkel cell carcinoma.,2009 Mar,"['Bialasiewicz, Seweryn', 'Lambert, Stephen B.', 'Whiley, David M.', 'Nissen, Michael D.', 'Sloots, Theo P.']",Emerg Infect Dis,,,True
46202621202a28e12bb2444d9f4b9763ed8b1881,PMC,Coordinated Implementation of Chikungunya Virus Reverse Transcription–PCR,http://dx.doi.org/10.3201/eid1503.081104,PMC2681123,19239767,NO-CC CODE,"A preformulated chikungunya virus real-time reverse transcription–PCR, quality-confirmed oligonucleotides, and noninfectious virus controls were distributed by the European Network for the Diagnosis of Imported Viral Diseases. An international proficiency study with 31 participants demonstrated that ad hoc implementation of molecular diagnostics was feasible and successful.",2009 Mar,"['Panning, Marcus', 'Charrel, Remi N.', 'Mantke, Oliver D.', 'Landt, Olfert', 'Niedrig, Matthias', 'Drosten, Christian']",Emerg Infect Dis,,,True
7f02b0d7567aa90c77c7fe13dc67f1bac185f88e,PMC,Human rhinoviruses: coming in from the cold,http://dx.doi.org/10.1186/gm44,PMC2684665,19439028,NO-CC CODE,"Rhinovirus infections cause at least 70% of virus-related wheezing exacerbations and cold and flu-like illnesses. Infections are also associated with otitis media, sinusitis and pneumonia. The annual impact of human rhinovirus (HRV) infections costs billions of healthcare dollars. To date, 100 serotyped HRV or 'classical' strains have been divided between two genetically distinct species based on subgenomic sequences, but many more, apparently novel strains remain un-characterized, circulating in unknown patterns and causing undefined illnesses. Until recently, the genomes of less than half the classical strains had been sequenced. In April 2009, the remaining classical HRV genome sequences were reported. These data will inform therapeutic development and phylogenetic analysis for this subset of HRV strains but should be viewed as one step in a long road leading to comprehensive HRV characterization.",2009 Apr 28,"['Arden, Katherine E', 'Mackay, Ian M']",Genome Med,,,True
dc13e186e4b8ca3e634b4c665fe07c124047e27e,PMC,"Novel Respiratory Virus Infections in Children, Brazil",http://dx.doi.org/10.3201/eid1505.081603,PMC2687000,19402976,NO-CC CODE,"Recently discovered respiratory viruses were detected in 19 (9.2%) of 205 nasal swab specimens from children in Brazil with respiratory illnesses. Five each were positive for human metapneumovirus (HMPV) alone and human bocavirus (HBoV) alone, 3 for human coronaviruses (HCoV-HKU1 or -NL63) alone, and 6 for more than 1 recently discovered virus.",2009 May,"['Albuquerque, Maria Carolina M.', 'Pena, Gisele P.A.', 'Varella, Rafael B.', 'Gallucci, George', 'Erdman, Dean', 'Santos, Norma']",Emerg Infect Dis,,,False
13157beaef7cf1c5fd5a90b3a77bf3917409cdb4,PMC,"Novel Respiratory Virus Infections in Children, Brazil",http://dx.doi.org/10.3201/eid1505.081603,PMC2687000,19402976,NO-CC CODE,"Recently discovered respiratory viruses were detected in 19 (9.2%) of 205 nasal swab specimens from children in Brazil with respiratory illnesses. Five each were positive for human metapneumovirus (HMPV) alone and human bocavirus (HBoV) alone, 3 for human coronaviruses (HCoV-HKU1 or -NL63) alone, and 6 for more than 1 recently discovered virus.",2009 May,"['Albuquerque, Maria Carolina M.', 'Pena, Gisele P.A.', 'Varella, Rafael B.', 'Gallucci, George', 'Erdman, Dean', 'Santos, Norma']",Emerg Infect Dis,,,True
2ea888daab5051a877778175c2349b630c5728f6,PMC,New Respiratory Enterovirus and Recombinant Rhinoviruses among Circulating Picornaviruses,http://dx.doi.org/10.3201/eid1505.081286,PMC2687021,19402957,NO-CC CODE,"Rhinoviruses and enteroviruses are leading causes of respiratory infections. To evaluate genotypic diversity and identify forces shaping picornavirus evolution, we screened persons with respiratory illnesses by using rhinovirus-specific or generic real-time PCR assays. We then sequenced the 5′ untranslated region, capsid protein VP1, and protease precursor 3CD regions of virus-positive samples. Subsequent phylogenetic analysis identified the large genotypic diversity of rhinoviruses circulating in humans. We identified and completed the genome sequence of a new enterovirus genotype associated with respiratory symptoms and acute otitis media, confirming the close relationship between rhinoviruses and enteroviruses and the need to detect both viruses in respiratory specimens. Finally, we identified recombinants among circulating rhinoviruses and mapped their recombination sites, thereby demonstrating that rhinoviruses can recombine in their natural host. This study clarifies the diversity and explains the reasons for evolution of these viruses.",2009 May,"['Tapparel, Caroline', 'Junier, Thomas', 'Gerlach, Daniel', 'Van Belle, Sandra', 'Turin, Lara', 'Cordey, Samuel', 'Mühlemann, Kathrin', 'Regamey, Nicolas', 'Aubert, John-David', 'Soccal, Paola M.', 'Eigenmann, Philippe', 'Zdobnov, Evgeny', 'Kaiser, Laurent']",Emerg Infect Dis,,,True
1c74b63f8be1bf0a381a36319751ddcac4f7f60c,PMC,New Respiratory Enterovirus and Recombinant Rhinoviruses among Circulating Picornaviruses,http://dx.doi.org/10.3201/eid1505.081286,PMC2687021,19402957,NO-CC CODE,"Rhinoviruses and enteroviruses are leading causes of respiratory infections. To evaluate genotypic diversity and identify forces shaping picornavirus evolution, we screened persons with respiratory illnesses by using rhinovirus-specific or generic real-time PCR assays. We then sequenced the 5′ untranslated region, capsid protein VP1, and protease precursor 3CD regions of virus-positive samples. Subsequent phylogenetic analysis identified the large genotypic diversity of rhinoviruses circulating in humans. We identified and completed the genome sequence of a new enterovirus genotype associated with respiratory symptoms and acute otitis media, confirming the close relationship between rhinoviruses and enteroviruses and the need to detect both viruses in respiratory specimens. Finally, we identified recombinants among circulating rhinoviruses and mapped their recombination sites, thereby demonstrating that rhinoviruses can recombine in their natural host. This study clarifies the diversity and explains the reasons for evolution of these viruses.",2009 May,"['Tapparel, Caroline', 'Junier, Thomas', 'Gerlach, Daniel', 'Van Belle, Sandra', 'Turin, Lara', 'Cordey, Samuel', 'Mühlemann, Kathrin', 'Regamey, Nicolas', 'Aubert, John-David', 'Soccal, Paola M.', 'Eigenmann, Philippe', 'Zdobnov, Evgeny', 'Kaiser, Laurent']",Emerg Infect Dis,,,False
dcc71f9181feb8632cf7a505099d278af3e6f67f,PMC,New Respiratory Enterovirus and Recombinant Rhinoviruses among Circulating Picornaviruses,http://dx.doi.org/10.3201/eid1505.081286,PMC2687021,19402957,NO-CC CODE,"Rhinoviruses and enteroviruses are leading causes of respiratory infections. To evaluate genotypic diversity and identify forces shaping picornavirus evolution, we screened persons with respiratory illnesses by using rhinovirus-specific or generic real-time PCR assays. We then sequenced the 5′ untranslated region, capsid protein VP1, and protease precursor 3CD regions of virus-positive samples. Subsequent phylogenetic analysis identified the large genotypic diversity of rhinoviruses circulating in humans. We identified and completed the genome sequence of a new enterovirus genotype associated with respiratory symptoms and acute otitis media, confirming the close relationship between rhinoviruses and enteroviruses and the need to detect both viruses in respiratory specimens. Finally, we identified recombinants among circulating rhinoviruses and mapped their recombination sites, thereby demonstrating that rhinoviruses can recombine in their natural host. This study clarifies the diversity and explains the reasons for evolution of these viruses.",2009 May,"['Tapparel, Caroline', 'Junier, Thomas', 'Gerlach, Daniel', 'Van Belle, Sandra', 'Turin, Lara', 'Cordey, Samuel', 'Mühlemann, Kathrin', 'Regamey, Nicolas', 'Aubert, John-David', 'Soccal, Paola M.', 'Eigenmann, Philippe', 'Zdobnov, Evgeny', 'Kaiser, Laurent']",Emerg Infect Dis,,,False
45dad2e0a82a6a22df9c573f868655018d5233f5,PMC,Use of Unstructured Event-Based Reports for Global Infectious Disease Surveillance,http://dx.doi.org/10.3201/eid1505.081114,PMC2687026,19402953,NO-CC CODE,"Free or low-cost sources of unstructured information, such as Internet news and online discussion sites, provide detailed local and near real-time data on disease outbreaks, even in countries that lack traditional public health surveillance. To improve public health surveillance and, ultimately, interventions, we examined 3 primary systems that process event-based outbreak information: Global Public Health Intelligence Network, HealthMap, and EpiSPIDER. Despite similarities among them, these systems are highly complementary because they monitor different data types, rely on varying levels of automation and human analysis, and distribute distinct information. Future development should focus on linking these systems more closely to public health practitioners in the field and establishing collaborative networks for alert verification and dissemination. Such development would further establish event-based monitoring as an invaluable public health resource that provides critical context and an alternative to traditional indicator-based outbreak reporting.",2009 May,"['Keller, Mikaela', 'Blench, Michael', 'Tolentino, Herman', 'Freifeld, Clark C.', 'Mandl, Kenneth D.', 'Mawudeku, Abla', 'Eysenbach, Gunther', 'Brownstein, John S.']",Emerg Infect Dis,,,True
d2fc91c08f376138ab8783e627db3f2e27d8c796,PMC,"Acceptance of Public Health Measures by Air Travelers, Switzerland",http://dx.doi.org/10.3201/eid1505.080933,PMC2687032,19402986,NO-CC CODE,,2009 May,"['Senpinar-Brunner, Nicole', 'Eckert, Tobias', 'Wyss, Kaspar']",Emerg Infect Dis,,,True
649e93103cd970604570c424279a7d6a53a99ef4,PMC,"Real-Time Surveillance for Respiratory Disease Outbreaks, Ontario, Canada",http://dx.doi.org/10.3201/eid1505.081174,PMC2687041,19402974,NO-CC CODE,"To validate the utility of a chief complaint–based emergency department surveillance system, we compared it with respiratory diagnostic data and calls to Telehealth Ontario about respiratory disease. This local syndromic surveillance system accurately monitored status of respiratory diseases in the community and contributed to early detection of respiratory disease outbreaks.",2009 May,"['van Dijk, Adam', 'Aramini, Jeff', 'Edge, Graham', 'Moore, Kieran M.']",Emerg Infect Dis,,,True
1d618133a3ebc9e6e55ba44933616cd0c07771cd,PMC,"Apes, lice and prehistory",http://dx.doi.org/10.1186/jbiol114,PMC2687769,19232074,NO-CC CODE,"Although most epidemic human infectious diseases are caused by recently introduced pathogens, cospeciation of parasite and host is commonplace for endemic infections. Occasional host infidelity, however, provides the endemic parasite with an opportunity to survive the potential extinction of its host. Such infidelity may account for the survival of certain types of human lice, and it is currently exemplified by viruses such as HIV.",2009 Feb 10,"Weiss, Robin A",J Biol,,,True
6fea38758661f89b35ac1bba4b6f78d58994d5bd,PMC,Silencing Viral MicroRNA as a Novel Antiviral Therapy?,http://dx.doi.org/10.1155/2009/419539,PMC2688686,19704916,NO-CC CODE,"Viruses are intracellular parasites that ensure their existence by converting host cells into viral particle producing entities or into hiding places rendering the virus invisible to the host immune system. Some viruses may also survive by transforming the infected cell into an immortal tumour cell. MicroRNAs are small non-coding transcripts that function as posttranscriptional regulators of gene expression. Viruses encode miRNAs that regulate expression of both cellular and viral genes, and contribute to the pathogenic properties of viruses. Hence, neutralizing the action of viral miRNAs expression by complementary single-stranded oligonucleotides or so-called anti-miRNAs may represent a strategy to combat viral infections and viral-induced pathogenesis. This review describes the miRNAs encoded by human viruses, and discusses the possible therapeutic applications of anti-miRNAs against viral diseases.",2009 May 28,"Moens, Ugo",J Biomed Biotechnol,,,True
9233087a44732e7cb754add5dd568b11f3dd8850,PMC,"Perceived Threat, Risk Perception, and Efficacy Beliefs Related to SARS and Other (Emerging) Infectious Diseases: Results of an International Survey",http://dx.doi.org/10.1007/s12529-008-9008-2,PMC2691522,19125335,NO-CC CODE,"PURPOSE: To study the levels of perceived threat, perceived severity, perceived vulnerability, response efficacy, and self-efficacy for severe acute respiratory syndrome (SARS) and eight other diseases in five European and three Asian countries. METHOD: A computer-assisted phone survey was conducted among 3,436 respondents. The questionnaire focused on perceived threat, vulnerability, severity, response efficacy, and self-efficacy related to SARS and eight other diseases. RESULTS: Perceived threat of SARS in case of an outbreak in the country was higher than that of other diseases. Perceived vulnerability of SARS was at an intermediate level and perceived severity was high compared to other diseases. Perceived threat for SARS varied between countries in Europe and Asia with a higher perceived severity of SARS in Europe and a higher perceived vulnerability in Asia. Response efficacy and self-efficacy for SARS were higher in Asia compared to Europe. In multiple linear regression analyses, country was strongly associated with perceived threat. CONCLUSIONS: The relatively high perceived threat for SARS indicates that it is seen as a public health risk and offers a basis for communication in case of an outbreak. The strong association between perceived threat and country and different regional patterns require further research.",2009 Mar 6,"['de Zwart, Onno', 'Veldhuijzen, Irene K.', 'Elam, Gillian', 'Aro, Arja R.', 'Abraham, Thomas', 'Bishop, George D.', 'Voeten, Hélène A. C. M.', 'Richardus, Jan Hendrik', 'Brug, Johannes']",Int J Behav Med,,,True
93dffbe2dbaf6a930a6ba69004962a4ccc4a4ddb,PMC,"Occasional review: Influenza in COPD: pathogenesis, prevention, and treatment",,PMC2692115,18044060,NO-CC CODE,"Influenza viruses cause respiratory tract infections that in patients with underlying lung diseases such as chronic obstructive pulmonary disease (COPD) are associated with exacerbations and excess morbidity and mortality. Typically, influenza B is associated with relatively mild, local outbreaks, whereas influenza A is the cause of world-wide pandemics. Upon infection, two antigens present on the viral surface, hemagglutinin and neuraminidase result in human immunity, but since many subtypes of these antigens exist that vary over time, immunity in the population is blunted. Vaccination is advocated in high-risk groups including patients with underlying (lung) diseases and in the elderly, and needs to be repeated annually with vaccines expected to cover the expected change in viral antigenicity. When started early, antiviral drugs, especially neuraminidase-inhibitors can be prescribed in adjunct to nonspecific interventions in an attempt to shorten disease duration and to prevent complications in case of an influenza infection. Currently, the effectiveness of antiviral drugs specifically in patients with COPD has not been proven.",2007 Mar,"Wesseling, Geertjan",Int J Chron Obstruct Pulmon Dis,,,True
a0ed0d8eecbfe77dad7e8c46acba3e9524422d66,PMC,Structural and Functional Bases for Broad-Spectrum Neutralization of Avian and Human Influenza A Viruses,http://dx.doi.org/10.1038/nsmb.1566,PMC2692245,19234466,NO-CC CODE,"Influenza virus remains a constant public health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Monoclonal antibody (mAb)-based immunotherapy is a promising strategy for disease control. Here we use a human Ab phage display library and H5 hemagglutinin (HA) ectodomain to select ten neutralizing mAbs (nAbs) with a remarkably broad range among Group 1 influenza viruses, including the H5N1 “bird flu” and the H1N1 “Spanish flu” strains. Notably, nine of the Abs utilize the same germline gene, VH1-69. The crystal structure of one mAb bound to H5N1 HA reveals that only the heavy chain inserts into a highly conserved pocket in the HA stem, inhibiting the conformational changes required for membrane fusion. Our studies indicate that nAbs targeting this pocket could provide broad protection against both seasonal and pandemic influenza A infections.",2009 Mar 22,"['Sui, Jianhua', 'Hwang, William C.', 'Perez, Sandra', 'Wei, Ge', 'Aird, Daniel', 'Chen, Li-mei', 'Santelli, Eugenio', 'Stec, Boguslaw', 'Cadwell, Greg', 'Ali, Maryam', 'Wan, Hongquan', 'Murakami, Akikazu', 'Yammanuru, Anuradha', 'Han, Thomas', 'Cox, Nancy J.', 'Bankston, Laurie A.', 'Donis, Ruben O.', 'Liddington, Robert C.', 'Marasco, Wayne A.']",Nat Struct Mol Biol,,,True
7af37cc39c5f2eeb88b98ea439da7fc687eddb60,PMC,In vivo transmission studies of ‘Candidatus Mycoplasma turicensis’ in the domestic cat,http://dx.doi.org/10.1051/vetres/2009028,PMC2701178,19505421,NO-CC CODE,"The natural transmission routes of the three feline haemotropic mycoplasmas – Mycoplasma haemofelis, ‘Candidatus Mycoplasma haemominutum’, and ‘Candidatus Mycoplasma turicensis’ (CMt) – are largely unknown. Since CMt has been detected in the saliva of infected cats using PCR, we hypothesised that direct transmission via social or aggressive contact may occur. The aim of this study was to evaluate this transmission route. CMt-positive saliva and blood samples were obtained from three prednisolone-treated specific pathogen-free (SPF) cats that were infected intraperitoneally with CMt. Five SPF cats were inoculated with CMt-positive saliva or blood subcutaneously to mimic cat bites, and five cats were inoculated orally with blood or oronasally with saliva to mimic social contact. Blood samples were monitored for CMt infection using quantitative real-time PCR and for seroconversion using a novel western blot assay. Neither oronasal nor subcutaneous inoculation with CMt-positive saliva led to CMt infection in the recipient cats, as determined by PCR, independent of prior prednisolone treatment. However, when blood containing the same CMt dose was given subcutaneously, 4 of the 5 cats became PCR-positive, while none of the 5 cats inoculated orally with up to 500 μL of CMt-positive blood became PCR-positive. Subsequently, the latter cats were successfully subcutaneously infected with blood. All 13 CMt-exposed cats seroconverted. In conclusion, CMt transmission by social contact seems less likely than transmission by aggressive interaction. The latter transmission may occur if the recipient cat is exposed to blood from an infected cat.",2009 May 16 Sep-Oct,"['Museux, Kristina', 'Boretti, Felicitas S.', 'Willi, Barbara', 'Riond, Barbara', 'Hoelzle, Katharina', 'Hoelzle, Ludwig E.', 'Wittenbrink, Max M.', 'Tasker, Séverine', 'Wengi, Nicole', 'Reusch, Claudia E.', 'Lutz, Hans', 'Hofmann-Lehmann, Regina']",Vet Res,,,True
49130444457c29a469a3d1c054c706c451975391,PMC,Recently published papers: small pieces of the puzzle and the long-term view,,PMC270692,12793868,NO-CC CODE,,2003 May 8,"Ball, Jonathan",Crit Care,,,True
65084f5b311cb50b0eca19c8f1a97ca89a69f5fb,PMC,Challenging beliefs and ethical concepts: the collateral damage of SARS,,PMC270701,12930546,NO-CC CODE,"The recent SARS (severe acute respiratory syndrome) outbreak exploded on an unsuspecting public and functionally paralyzed health care delivery systems in many countries. Cancer treatments were deferred and elective surgeries, clinic visits and diagnostic tests were postponed. Other collateral damage includes the devastating psychological distress suffered by patients who were isolated from their families, those same families who could not visit their ill loved ones, patients awaiting access to various aspects of the health care system, and health care workers. We are all starting to dig out, and this process will take many months at a minimum and we may never completely return to the way we were. This commentary addresses the implications of a modern-day epidemic like SARS, focusing on the intensive care unit setting, with special attention given to the effect on health care workers. We explore some of the ethical challenges posed to relationships, professional integrity and resource allocation.",2003 May 29,"['Bernstein, Mark', 'Hawryluck, Laura']",Crit Care,,,True
22279bef01140a61dda67aad293824d04f6bcc23,PMC,"Recently published papers: inflammation, elucidation, manipulation?",,PMC270703,12930550,NO-CC CODE,,2003 Jul 3,"['Kirk-Bayley, Justin', 'Venn, Richard']",Crit Care,,,True
ae267a98af103856a22932cac54e9208b34da846,PMC,Resistance of livestock to viruses: mechanisms and strategies for genetic engineering,http://dx.doi.org/10.1186/1297-9686-28-5-385,PMC2708302,,NO-CC CODE,,1996 Dec 15,"Gavora, JS",Genet Sel Evol,,,True
e8b5cb3fc6da16eb2ffe2830a159b3aa9c04577d,PMC,Is the risk of multiple sclerosis related to the ‘biography’ of the immune system?,http://dx.doi.org/10.1007/s00415-009-5068-8,PMC2708340,19252771,NO-CC CODE,"Multiple sclerosis (MS) with onset in childhood offers a unique opportunity to study the infectious background of this disease but the immune reactions against infectious agents in such children have only recently been investigated. These and other epidemiological studies strongly implicate involvement of one or more infectious agents in the aetiology of MS, with Epstein-Barr virus (EBV) being the prime candidate. Rather than being the actual cause of MS, it is more probable that these agents are involved in the development of immunoregulatory pathways. These pathways, if disturbed by hygiene-related factors including an altered sequence of infections, may generate and maintain a deficit within the immunological network that facilitates, to particular early events in the development of MS, preceding the onset of MS disease by years or a decade. A framework that can serve as a guide for further epidemiological, immunologic and molecular biologic investigations is formulated. This approach may shed light on the complex natural history of MS and may lead to rational preventive and therapeutic strategies. It is possible that, in the future, MS could be prevented by vaccination against EBV in early childhood; the framework is of relevance to the design of an appropriate type of vaccine.",2009 Jul 1,"['Krone, Bernd', 'Oeffner, Frank', 'Grange, John M.']",J Neurol,,,True
670ef52bc9d875ae6086b6b76d739fe85652ab6c,PMC,Vasoactive neuropeptides in clinical ophthalmology: An association with autoimmune retinopathy?,,PMC2709019,19668576,NO-CC CODE,"The mammalian eye is protected against pathogens and inflammation in a relatively immune-privileged environment. Stringent mechanisms are activated that regulate external injury, infection, and autoimmunity. The eye contains a variety of cells expressing vasoactive neuropeptides (VNs), and their receptors, located in the sclera, cornea, iris, ciliary body, ciliary process, and the retina. VNs are important activators of adenylate cyclase, deriving cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). Impairment of VN function would arguably impede cAMP production and impede utilization of ATP. Thus VN autoimmunity may be an etiological factor in retinopathy involving perturbations of purinergic signaling. A sound blood supply is necessary for the existence and functional properties of the retina. This paper postulates that impairments in the endothelial barriers and the blood–retinal barrier, as well as certain inflammatory responses, may arise from disruption to VN function. Phosphodiesterase inhibitors and purinergic modulators may have a role in the treatment of postulated VN autoimmune retinopathy.",2009 Jun 2,"['Staines, Donald R', 'Brenu, Ekua W', 'Marshall-Gradisnik, Sonya']",Clin Ophthalmol,,,True
d9642448d10a480b44672fcdb066ca3deff8031e,PMC,Effectiveness of national cervical cancer screening programme in Taiwan: 12-year experiences,http://dx.doi.org/10.1038/sj.bjc.6605139,PMC2713714,19536091,NO-CC CODE,"BACKGROUND: We examined cervical cancer incidence before and after nationwide cervical cancer screening was initiated in Taiwan in mid-1995. RESULTS: The invasive cancer incidence decreased by 47.8% during 1995–2006. The carcinoma in situ incidence increased 1.7-fold during 1995–2000, and decreased by 19.6% during 2000–2006. CONCLUSION: The Taiwan national programme has significantly decreased invasive cervical cancer.",2009 Jul 7,"['Chen, Y-Y', 'You, S-L', 'Chen, C-A', 'Shih, L-Y', 'Koong, S-L', 'Chao, K-Y', 'Hsiao, M-L', 'Hsieh, C-Y', 'Chen, C-J']",Br J Cancer,,,True
4b4c47bbc2473d07c8ffd4d940a099e7546b9f25,PMC,Regulation of the apoptosis-inducing kinase DRAK2 by cyclooxygenase-2 in colorectal cancer,http://dx.doi.org/10.1038/sj.bjc.6605144,PMC2720240,19638987,NO-CC CODE,"BACKGROUND: Cyclooxygenase-2 (COX-2) is over-expressed in colorectal cancer (CRC), rendering tumour cells resistant to apoptosis. Selective COX-2 inhibition is effective in CRC prevention, although having adverse cardiovascular effects, thus focus has shifted to downstream pathways. METHODS: Microarray experiments identified genes regulated by COX-2 in HCA7 CRC cells. In vitro and in vivo regulation of DRAK2 (DAP kinase-related apoptosis-inducing kinase 2 or STK17β, an apoptosis-inducing kinase) by COX-2 was validated by qRT-PCR. RESULTS: Inhibition of COX-2 induced apoptosis and enhanced DRAK2 expression in HCA7 cells (4.4-fold increase at 4 h by qRT-PCR, P=0.001), an effect prevented by co-administration of PGE(2). DRAK2 levels were suppressed in a panel of human colorectal tumours (n=10) compared to normal mucosa, and showed inverse correlation with COX-2 expression (R=−0.68, R(2)=0.46, P=0.03). Administration of the selective COX-2 inhibitor rofecoxib to patients with CRC (n=5) induced DRAK2 expression in tumours (2.5-fold increase, P=0.01). In vitro silencing of DRAK2 by RNAi enhanced CRC cell survival following COX-2 inhibitor treatment. CONCLUSION: DRAK2 is a serine–threonine kinase implicated in the regulation of apoptosis and is negatively regulated by COX-2 in vitro and in vivo, suggesting a novel mechanism for the effect of COX-2 on cancer cell survival.",2009 Aug 4,"['Doherty, G A', 'Byrne, S M', 'Austin, S C', 'Scully, G M', 'Sadlier, D M', 'Neilan, T G', 'Kay, E W', 'Murray, F E', 'Fitzgerald, D J']",Br J Cancer,,,True
7e4f3fdf70d647d0530a94f12f90f0927fbc1ff5,PMC,Biological targets for isatin and its analogues: Implications for therapy,,PMC2721300,19707325,NO-CC CODE,"Isatin and its metabolites are constituents of many natural substances. They are also components of many synthetic compounds exhibiting a wide range of effects, including antiviral activity, antitumor and antiangiogenic activity, antibacterial, antitubercular, antifungal, antiaptotic, anticonvulsant and anxyolytic activities. Isatin itself is an endogenous oxidized indole with a wide spectrum of behavioral and metabolic effects. It has a distinct and discontinuous distribution in the brain, peripheral tissues and body fluids and isatin binding sites are widely distributed also. Its output is increased during stress. Its most potent known in vitro actions are as an antagonist of atrial natriuretic peptide (ANP) function and NO signaling. As we understand more about its function and sites of action we may be able to develop new pharmacological agents to mimic or counteract its activity. We consider here the most promising biological targets for various isatin analogues and/or metabolites, which are employed for the development of various groups of therapeutics. It is also possible that the level of endogenous isatin may influence the in vivo pharmacological activity of compounds possessing the isatin moiety.",2007 Jun,"['Medvedev, Alexei', 'Buneeva, Olga', 'Glover, Vivette']",Biologics,,,True
041827953afeda8e10e25ae78437e37f8a453578,PMC,Generation and Characterization of Novel Human IRAS Monoclonal Antibodies,http://dx.doi.org/10.1155/2009/973754,PMC2723995,19672324,NO-CC CODE,"Imidazoline receptors were first proposed by Bousquet et al., when they studied antihypertensive effect of clonidine. A strong candidate for I1R, known as imidazoline receptor antisera-selected protein (IRAS), has been cloned from human hippocampus. We reported that IRAS mediated agmatine-induced inhibition of opioid dependence in morphine-dependent cells. To elucidate the functional and structure properties of I1R, we developed the newly monoclonal antibody against the N-terminal hIRAS region including the PX domain (10–120aa) through immunization of BALB/c mice with the NusA-IRAS fusion protein containing an IRAS N-terminal (10–120aa). Stable hybridoma cell lines were established and monoclonal antibodies specifically recognized full-length IRAS proteins in their native state by immunoblotting and immunoprecipitation. Monoclonal antibodies stained in a predominantly punctate cytoplasmic pattern when applied to IRAS-transfected HEK293 cells by indirect immunofluorescence assays and demonstrated excellent reactivity in flow immunocytometry. These monoclonal antibodies will provide powerful reagents for the further investigation of hIRAS protein functions.",2009 Aug 10,"['Wang, Bo', 'Liu, Ying', 'Shan, Yajun', 'Yao, Zhenyu', 'Liu, Xiaolan', 'Su, Ruibin', 'Sun, Qihong', 'Cong, Yuwen', 'Li, Jin']",J Biomed Biotechnol,,,True
f1e47847b222b58ed3c6cc35c785b1136c388019,PMC,Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype,http://dx.doi.org/10.1038/labinvest.2009.32,PMC2725397,19398961,NO-CC CODE,"Recent studies in mice have demonstrated that the protein tyrosine phosphatase SHP-1 is a crucial negative regulator of pro-inflammatory cytokine signaling, TLR signaling, and inflammatory gene expression. Furthermore, mice genetically lacking SHP-1 (me/me) display a profound susceptibility to inflammatory CNS demyelination relative to wild type mice. In particular, SHP-1 deficiency may act predominantly in inflammatory macrophages to increase CNS demyelination as SHP-1-deficient macrophages display co-expression of inflammatory effector molecules and increased demyelinating activity in me/me mice. Recently, we reported that PBMCs of multiple sclerosis (MS) patients have a deficiency in SHP-1 expression relative to normal control subjects indicating that SHP-1 deficiency may play a similar role in MS as to that seen in mice. Therefore, it became essential to examine the specific expression and function of SHP-1 in macrophages from MS patients. Herein, we document that macrophages of MS patients have deficient SHP-1 protein and mRNA expression relative to those of normal control subjects. To examine functional consequences of the lower SHP-1, the activation of STAT6, STAT1, and NF-κB was quantified and macrophages of MS patients showed increased activation of these transcription factors. In accordance with this observation, several STAT6-, STAT1-, and NF-κB-responsive genes that mediate inflammatory demyelination were increased in macrophages of MS patients following cytokine and TLR agonist stimulation. Supporting a direct role of SHP-1 deficiency in altered macrophage function, experimental depletion of SHP-1 in normal subject macrophages resulted in an increased STAT/NF-κB activation and increased inflammatory gene expression to levels seen in macrophages of MS patients. In conclusion, macrophages of MS patients display a deficiency of SHP-1 expression, heightened activation of STAT6, STAT1, and NF-κB and a corresponding inflammatory profile that may be important in controlling macrophage-mediated demyelination in MS.",2009 Jul 27,"['Christophi, George P.', 'Panos, Michael', 'Hudson, Chad A.', 'Christophi, Rebecca L.', 'Gruber, Ross C.', 'Mersich, Akos T.', 'Blystone, Scott D.', 'Jubelt, Burk', 'Massa, Paul T.']",Lab Invest,,,True
96b1d037fb00eb3ecb7321ca5102d36553ff56ce,PMC,"Human Bocavirus Infection, People’s Republic of China",http://dx.doi.org/10.3201/eid1301.060824,PMC2725817,17370538,NO-CC CODE,"A newly identified parvovirus, human bocavirus (HBoV), was found in 21 (8.3%) of 252 nasopharyngeal aspirates from hospitalized children with lower respiratory tract infection in Hunan Province, People’s Republic of China. Viral loads were 10(4) to 10(10) copies/mL. Phylogenetic analysis of the VP1 gene showed a single genetic lineage of HBoV worldwide.",2007 Jan,"['Qu, Xiao-Wang', 'Duan, Zhao-Jun', 'Qi, Zheng-Yu', 'Xie, Zhi-Ping', 'Gao, Han-Chun', 'Liu, Wen-Pei', 'Huang, Can-Ping', 'Peng, Fu-Wang', 'Zheng, Li-Shu', 'Hou, Yun-De']",Emerg Infect Dis,,,True
f194d114007cfcecb07bcfc17b26256ea82cc46e,PMC,Panmicrobial Oligonucleotide Array for Diagnosis of Infectious Diseases,http://dx.doi.org/10.3201/eid1301.060837,PMC2725825,17370518,NO-CC CODE,"To facilitate rapid, unbiased, differential diagnosis of infectious diseases, we designed GreeneChipPm, a panmicrobial microarray comprising 29,455 sixty-mer oligonucleotide probes for vertebrate viruses, bacteria, fungi, and parasites. Methods for nucleic acid preparation, random primed PCR amplification, and labeling were optimized to allow the sensitivity required for application with nucleic acid extracted from clinical materials and cultured isolates. Analysis of nasopharyngeal aspirates, blood, urine, and tissue from persons with various infectious diseases confirmed the presence of viruses and bacteria identified by other methods, and implicated Plasmodium falciparum in an unexplained fatal case of hemorrhagic feverlike disease during the Marburg hemorrhagic fever outbreak in Angola in 2004–2005.",2007 Jan,"['Palacios, Gustavo', 'Quan, Phenix-Lan', 'Jabado, Omar J.', 'Conlan, Sean', 'Hirschberg, David L.', 'Liu, Yang', 'Zhai, Junhui', 'Renwick, Neil', 'Hui, Jeffrey', 'Hegyi, Hedi', 'Grolla, Allen', 'Strong, James E.', 'Towner, Jonathan S.', 'Geisbert, Thomas W.', 'Jahrling, Peter B.', 'Büchen-Osmond, Cornelia', 'Ellerbrok, Heinz', 'Sanchez-Seco, Maria Paz', 'Lussier, Yves', 'Formenty, Pierre', 'Nichol, Stuart T.', 'Feldmann, Heinz', 'Briese, Thomas', 'Lipkin, W. Ian']",Emerg Infect Dis,,,True
fc154cdab53513c3beb93049b93dcc34602c921a,PMC,"Wildlife, Exotic Pets, and Emerging Zoonoses",http://dx.doi.org/10.3201/eid1301.060480,PMC2725831,17370509,NO-CC CODE,"Most emerging infectious diseases are zoonotic; wildlife constitutes a large and often unknown reservoir. Wildlife can also be a source for reemergence of previously controlled zoonoses. Although the discovery of such zoonoses is often related to better diagnostic tools, the leading causes of their emergence are human behavior and modifications to natural habitats (expansion of human populations and their encroachment on wildlife habitat), changes in agricultural practices, and globalization of trade. However, other factors include wildlife trade and translocation, live animal and bushmeat markets, consumption of exotic foods, development of ecotourism, access to petting zoos, and ownership of exotic pets. To reduce risk for emerging zoonoses, the public should be educated about the risks associated with wildlife, bushmeat, and exotic pet trades; and proper surveillance systems should be implemented.",2007 Jan,"['Chomel, Bruno B.', 'Belotto, Albino', 'Meslin, François-Xavier']",Emerg Infect Dis,,,True
c54608c457676be2a819a1879a14df08074082d1,PMC,"Human Bocavirus in Febrile Children, the Netherlands",http://dx.doi.org/10.3201/eid1301.060819,PMC2725834,17370546,NO-CC CODE,,2007 Jan,"['Monteny, Miriam', 'Niesters, Hubert G.M.', 'Moll, Henriëtte A.', 'Berger, Marjolein Y.']",Emerg Infect Dis,,,True
2b74ca42f9a1083f01aeb7e7ee221953b2ed57fc,PMC,"Interaction Between Humans and Poultry, Rural Cambodia",http://dx.doi.org/10.3201/eid1301.061014,PMC2725837,17370527,NO-CC CODE,"Because avian influenza H5N1 infection risks are associated with exposure to infected poultry, we conducted a knowledge, attitudes, and practices survey of poultry-handling behavior among villagers in rural Cambodia. Despite widespread knowledge of avian influenza and personal protection measures, most rural Cambodians still have a high level of at-risk poultry handling.",2007 Jan,"['Ly, Sowath', 'Van Kerkhove, Maria D.', 'Holl, Davun', 'Froehlich, Yves', 'Vong, Sirenda']",Emerg Infect Dis,,,True
d01a3aa9bfabf76255cad83bb3aef2e5773f2d1c,PMC,"Code-based Syndromic Surveillance for Influenzalike Illness by International Classification of Diseases, Ninth Revision",http://dx.doi.org/10.3201/eid1302.060557,PMC2725845,17479881,NO-CC CODE,"With the spread of avian influenza, use of automated data streams to rapidly detect and track human influenza cases has increased. We performed correlation analyses to determine whether International Classification of Diseases, Ninth Revision (ICD-9), groupings used to detect influenzalike illness (ILI) within an automated syndromic system correlate with respiratory virus laboratory test results in the same population (r = 0.71 or 0.86, depending on group). We used temporal and signal-to-noise analysis to identify 2 subsets of ICD-9 codes that most accurately represent ILI trends, compared nationwide sentinel ILI surveillance data from the Centers for Disease Control and Prevention with the automated data (r = 0.97), and found the most sensitive set of ICD-9 codes for respiratory illness surveillance. Our results demonstrate a method for selecting the best group of ICD-9 codes to assist system developers and health officials who are interpreting similar data for daily public health activities.",2007 Feb,"['Marsden-Haug, Nicola', 'Foster, Virginia B.', 'Gould, Philip L.', 'Elbert, Eugene', 'Wang, Hailiang', 'Pavlin, Julie A.']",Emerg Infect Dis,,,True
357d5838127aad0439fe56f9a619d11919e51d01,PMC,"Avian Influenza Risk Perception, Europe and Asia",http://dx.doi.org/10.3201/eid1302.060303,PMC2725846,17479894,NO-CC CODE,"During autumn 2005, we conducted 3,436 interviews in European and Asian countries. We found risk perceptions of avian influenza to be at an intermediate level and beliefs of efficacy to be slightly lower. Risk perceptions were higher in Asia than Europe; efficacy beliefs were lower in Europe than Asia.",2007 Feb,"['de Zwart, Onno', 'Veldhuijzen, Irene K.', 'Elam, Gillian', 'Aro, Arja R.', 'Abraham, Thomas', 'Bishop, George D.', 'Richardus, Jan Hendrik', 'Brug, Johannes']",Emerg Infect Dis,,,True
2b239fe6cdaea749fbfd5c219b70ceb99ba5a844,PMC,Rapid Genome Sequencing of RNA Viruses,http://dx.doi.org/10.3201/eid1302.061032,PMC2725858,17479903,NO-CC CODE,We developed a system for rapid determination of viral RNA sequences whereby genomic sequence is obtained from cultured virus isolates without subcloning into plasmid vectors. This method affords new opportunities to address the challenges of unknown or untypeable emerging viruses.,2007 Feb,"['Mizutani, Tetsuya', 'Endoh, Daiji', 'Okamoto, Michiko', 'Shirato, Kazuya', 'Shimizu, Hiroyuki', 'Arita, Minetaro', 'Fukushi, Shuetsu', 'Saijo, Masayuki', None, None, 'Lim, Chang Kweng', 'Ito, Mikako', 'Nerome, Reiko', 'Takasaki, Tomohiko', 'Ishii, Koji', 'Suzuki, Tetsuro', 'Kurane, Ichiro', 'Morikawa, Shigeru', 'Nishimura, Hidekazu']",Emerg Infect Dis,,,True
63b48a2db91293fd73f193d76cad74360b561706,PMC,Subclinical Infection with Avian Influenza A H5N1 Virus in Cats,http://dx.doi.org/10.3201/eid1302.060608,PMC2725870,17479886,NO-CC CODE,"Avian influenza A virus subtype H5N1 was transmitted to domestic cats by close contact with infected birds. Virus-specific nucleic acids were detected in pharyngeal swabs from 3 of 40 randomly sampled cats from a group of 194 animals (day 8 after contact with an infected swan). All cats were transferred to a quarantine station and monitored for clinical signs, virus shedding, and antibody production until day 50. Despite unfamiliar handling, social distress and the presence of other viral and nonviral pathogens that caused illness and poor health and compromised the immune systems, none of the cats developed clinical signs of influenza. There was no evidence of horizontal transmission to other cats because only 2 cats developed antibodies against H5N1 virus.",2007 Feb,"['Leschnik, Michael', 'Weikel, Joachim', 'Möstl, Karin', 'Revilla-Fernández, Sandra', 'Wodak, Eveline', 'Bagó, Zoltan', 'Vanek, Elisabeth', 'Benetka, Viviane', 'Hess, Michael', 'Thalhammer, Johann G.']",Emerg Infect Dis,,,True
ecd8bd486e5e3d2c0604ba6e4f5f13d8589ab386,PMC,Effectiveness of Neuraminidase Inhibitors for Preventing Staff Absenteeism during Pandemic Influenza,http://dx.doi.org/10.3201/eid1303.060309,PMC2725890,17552099,NO-CC CODE,"We used a deterministic SEIR (susceptible-exposed-infectious-removed) meta-population model, together with scenario, sensitivity, and simulation analyses, to determine stockpiling strategies for neuraminidase inhibitors that would minimize absenteeism among healthcare workers. A pandemic with a basic reproductive number (R(0)) of 2.5 resulted in peak absenteeism of 10%. Treatment decreased peak absenteeism to 8%, while 8 weeks’ prophylaxis reduced it to 2%. For pandemics with higher R(0), peak absenteeism exceeded 20% occasionally and 6 weeks’ prophylaxis reduced peak absenteeism by 75%. Insufficient duration of prophylaxis increased peak absenteeism compared with treatment only. Earlier pandemic detection and initiation of prophylaxis may render shorter prophylaxis durations ineffective. Eight weeks’ prophylaxis substantially reduced peak absenteeism under a broad range of assumptions for severe pandemics (peak absenteeism >10%). Small investments in treatment and prophylaxis, if adequate and timely, can reduce absenteeism among essential staff.",2007 Mar,"['Lee, Vernon J.', 'Chen, Mark I.']",Emerg Infect Dis,,,False
218e334c991ac7840a535ceddb2ac7e026a4919e,PMC,Effectiveness of Neuraminidase Inhibitors for Preventing Staff Absenteeism during Pandemic Influenza,http://dx.doi.org/10.3201/eid1303.060309,PMC2725890,17552099,NO-CC CODE,"We used a deterministic SEIR (susceptible-exposed-infectious-removed) meta-population model, together with scenario, sensitivity, and simulation analyses, to determine stockpiling strategies for neuraminidase inhibitors that would minimize absenteeism among healthcare workers. A pandemic with a basic reproductive number (R(0)) of 2.5 resulted in peak absenteeism of 10%. Treatment decreased peak absenteeism to 8%, while 8 weeks’ prophylaxis reduced it to 2%. For pandemics with higher R(0), peak absenteeism exceeded 20% occasionally and 6 weeks’ prophylaxis reduced peak absenteeism by 75%. Insufficient duration of prophylaxis increased peak absenteeism compared with treatment only. Earlier pandemic detection and initiation of prophylaxis may render shorter prophylaxis durations ineffective. Eight weeks’ prophylaxis substantially reduced peak absenteeism under a broad range of assumptions for severe pandemics (peak absenteeism >10%). Small investments in treatment and prophylaxis, if adequate and timely, can reduce absenteeism among essential staff.",2007 Mar,"['Lee, Vernon J.', 'Chen, Mark I.']",Emerg Infect Dis,,,True
d754e10693704ae712d206a81db8c7e68037ebc9,PMC,Effectiveness of Neuraminidase Inhibitors for Preventing Staff Absenteeism during Pandemic Influenza,http://dx.doi.org/10.3201/eid1303.060309,PMC2725890,17552099,NO-CC CODE,"We used a deterministic SEIR (susceptible-exposed-infectious-removed) meta-population model, together with scenario, sensitivity, and simulation analyses, to determine stockpiling strategies for neuraminidase inhibitors that would minimize absenteeism among healthcare workers. A pandemic with a basic reproductive number (R(0)) of 2.5 resulted in peak absenteeism of 10%. Treatment decreased peak absenteeism to 8%, while 8 weeks’ prophylaxis reduced it to 2%. For pandemics with higher R(0), peak absenteeism exceeded 20% occasionally and 6 weeks’ prophylaxis reduced peak absenteeism by 75%. Insufficient duration of prophylaxis increased peak absenteeism compared with treatment only. Earlier pandemic detection and initiation of prophylaxis may render shorter prophylaxis durations ineffective. Eight weeks’ prophylaxis substantially reduced peak absenteeism under a broad range of assumptions for severe pandemics (peak absenteeism >10%). Small investments in treatment and prophylaxis, if adequate and timely, can reduce absenteeism among essential staff.",2007 Mar,"['Lee, Vernon J.', 'Chen, Mark I.']",Emerg Infect Dis,,,True
7e1c6ccf9c329afc2fbb53e028c9412a61c25926,PMC,Pregnancy and Emerging Diseases,http://dx.doi.org/10.3201/eid1303.061345,PMC2725895,17552124,NO-CC CODE,,2007 Mar,"Anker, Martha",Emerg Infect Dis,,,True
dce54cded1eacab0a9aa40c210a4b27ea9fd2226,PMC,"Matrix Protein 2 Vaccination and Protection against Influenza Viruses, Including Subtype H5N1",http://dx.doi.org/10.3201/eid1303.061125,PMC2725899,17552096,NO-CC CODE,"Changes in influenza viruses require regular reformulation of strain-specific influenza vaccines. Vaccines based on conserved antigens provide broader protection. Influenza matrix protein 2 (M2) is highly conserved across influenza A subtypes. To evaluate its efficacy as a vaccine candidate, we vaccinated mice with M2 peptide of a widely shared consensus sequence. This vaccination induced antibodies that cross-reacted with divergent M2 peptide from an H5N1 subtype. A DNA vaccine expressing full-length consensus-sequence M2 (M2-DNA) induced M2-specific antibody responses and protected against challenge with lethal influenza. Mice primed with M2-DNA and then boosted with recombinant adenovirus expressing M2 (M2-Ad) had enhanced antibody responses that cross-reacted with human and avian M2 sequences and induced T-cell responses. This M2 prime-boost vaccination conferred broad protection against challenge with lethal influenza A, including an H5N1 strain. Vaccination with M2, with key sequences represented, may provide broad protection against influenza A.",2007 Mar,"['Tompkins, Stephen Mark', 'Zhao, Zi-Shan', 'Lo, Chia-Yun', 'Misplon, Julia A.', 'Liu, Teresa', 'Ye, Zhiping', 'Hogan, Robert J.', 'Wu, Zhengqi', 'Benton, Kimberly A.', 'Tumpey, Terrence M.', 'Epstein, Suzanne L.']",Emerg Infect Dis,,,True
e06405cc150773e699a28a474e50a5e579939f89,PMC,Bird Migration Routes and Risk for Pathogen Dispersion into Western Mediterranean Wetlands,http://dx.doi.org/10.3201/eid1303.060301,PMC2725901,17552088,NO-CC CODE,"Wild birds share with humans the capacity for moving fast over large distances. During migratory movements, birds carry pathogens that can be transmitted between species at breeding, wintering, and stopover places where numerous birds of various species are concentrated. We consider the area of the Camargue (southern France) as an example to highlight how ad hoc information already available on birds’ movements, abundance, and diversity can help assess the introduction and transmission risk for birdborne diseases in the western Mediterranean wetlands. Avian influenza and West Nile viruses are used as examples because birds are central to the epidemiology of these viruses.",2007 Mar,"['Jourdain, Elsa', 'Gauthier-Clerc, Michel', 'Bicout, Dominique', 'Sabatier, Philippe']",Emerg Infect Dis,,,True
a6f4882f1c3862d065c63f0f352541404aed8143,PMC,Bird Migration Routes and Risk for Pathogen Dispersion into Western Mediterranean Wetlands,http://dx.doi.org/10.3201/eid1303.060301,PMC2725901,17552088,NO-CC CODE,"Wild birds share with humans the capacity for moving fast over large distances. During migratory movements, birds carry pathogens that can be transmitted between species at breeding, wintering, and stopover places where numerous birds of various species are concentrated. We consider the area of the Camargue (southern France) as an example to highlight how ad hoc information already available on birds’ movements, abundance, and diversity can help assess the introduction and transmission risk for birdborne diseases in the western Mediterranean wetlands. Avian influenza and West Nile viruses are used as examples because birds are central to the epidemiology of these viruses.",2007 Mar,"['Jourdain, Elsa', 'Gauthier-Clerc, Michel', 'Bicout, Dominique', 'Sabatier, Philippe']",Emerg Infect Dis,,,False
f3e1f3dc98f076fcddab0fa95dc3eeb89072265f,PMC,Bird Migration Routes and Risk for Pathogen Dispersion into Western Mediterranean Wetlands,http://dx.doi.org/10.3201/eid1303.060301,PMC2725901,17552088,NO-CC CODE,"Wild birds share with humans the capacity for moving fast over large distances. During migratory movements, birds carry pathogens that can be transmitted between species at breeding, wintering, and stopover places where numerous birds of various species are concentrated. We consider the area of the Camargue (southern France) as an example to highlight how ad hoc information already available on birds’ movements, abundance, and diversity can help assess the introduction and transmission risk for birdborne diseases in the western Mediterranean wetlands. Avian influenza and West Nile viruses are used as examples because birds are central to the epidemiology of these viruses.",2007 Mar,"['Jourdain, Elsa', 'Gauthier-Clerc, Michel', 'Bicout, Dominique', 'Sabatier, Philippe']",Emerg Infect Dis,,,False
e40be79a3cf1f325f186e5b8adb087211f5ebc56,PMC,"Spanish Influenza in Japanese Armed Forces, 1918–1920",http://dx.doi.org/10.3201/eid1304.060615,PMC2725954,17553274,NO-CC CODE,"With the recent outbreaks of avian influenza A (H5N1), the risk for the next influenza pandemic has increased. For effective countermeasures against the next pandemic, investigation of past pandemics is necessary. We selected cases diagnosed as influenza from medical records and hospitalization registries of Japanese army hospitals during 1918–1920, the Spanish influenza era, and investigated clinical features and circumstances of outbreaks. Admission lists showed a sudden increase in the number of inpatients with influenza in November 1918 and showed the effect of the first wave of this pandemic in Tokyo. The death rate was high (6%–8%) even though patients were otherwise healthy male adults.",2007 Apr,"['Kawana, Akihiko', 'Naka, Go', 'Fujikura, Yuji', 'Kato, Yasuyuki', 'Mizuno, Yasutaka', 'Kondo, Tatsuya', 'Kudo, Koichiro']",Emerg Infect Dis,,,True
97a632fdbc3ebd9ace9c84c90229bfa08e166ecd,PMC,Effectiveness of Interventions to Reduce Contact Rates during a Simulated Influenza Pandemic,http://dx.doi.org/10.3201/eid1304.060828,PMC2725959,17553273,NO-CC CODE,"Measures to decrease contact between persons during an influenza pandemic have been included in pandemic response plans. We used stochastic simulation models to explore the effects of school closings, voluntary confinements of ill persons and their household contacts, and reductions in contacts among long-term care facility (LTCF) residents on pandemic-related illness and deaths. Our findings suggest that school closings would not have a substantial effect on pandemic-related outcomes in the absence of measures to reduce out-of-school contacts. However, if persons with influenzalike symptoms and their household contacts were encouraged to stay home, then rates of illness and death might be reduced by ≈50%. By preventing ill LTCF residents from making contact with other residents, illness and deaths in this vulnerable population might be reduced by ≈60%. Restricting the activities of infected persons early in a pandemic could decrease negative health impact.",2007 Apr,"['Haber, Michael J.', 'Shay, Davis K.', 'Davis, Xiaohong M.', 'Patel, Rajan', 'Jin, Xiaoping', 'Weintraub, Eric', 'Orenstein, Evan', 'Thompson, William W.']",Emerg Infect Dis,,,True
762d9040c711ef9f7ad28c28b7d4b65f9e51296d,PMC,Dengue and Relative Bradycardia,http://dx.doi.org/10.3201/eid1304.061212,PMC2725972,17561566,NO-CC CODE,,2007 Apr,"['Lateef, Aisha', 'Fisher, Dale Andrew', 'Tambyah, Paul Ananth']",Emerg Infect Dis,,,True
ed7a04f26d6e08daab64aa8f7fb5bac8da9e0bad,PMC,"Human Bocavirus, a Respiratory and Enteric Virus",http://dx.doi.org/10.3201/eid1304.061501,PMC2725986,17553287,NO-CC CODE,"In Spain, human bocavirus (HBoV) was detected in 48 (9.1%) of 527 children with gastroenteritis at similar frequency as for children with respiratory illness (40/520, 7.7%). Fecal excretion adds new concern about the transmission of HBoV. To our knowledge, this report is the first to document HBoV in human feces.",2007 Apr,"['Vicente, Diego', 'Cilla, Gustavo', 'Montes, Milagrosa', 'Pérez-Yarza, Eduardo G.', 'Pérez-Trallero, Emilio']",Emerg Infect Dis,,,True
e12c17bb3bd456ef264c863eca4a393c532f065e,PMC,Novel and Re-emerging Respiratory Viral Diseases: Novartis Foundation Symposium 290,http://dx.doi.org/10.3201/eid1506.090293,PMC2727329,,NO-CC CODE,,2009 Jun,"Morens, David M.",Emerg Infect Dis,,,False
118d16b3829c6880298058627442bdc06591be6e,PMC,"Japanese Encephalitis Viruses from Bats in Yunnan, China",http://dx.doi.org/10.3201/eid1506.081525,PMC2727346,19523297,NO-CC CODE,"Genome sequencing and virulence studies of 2 Japanese encephalitis viruses (JEVs) from bats in Yunnan, China, showed a close relationship with JEVs isolated from mosquitoes and humans in the same region over 2 decades. These results indicate that bats may play a role in human Japanese encephalitis outbreaks in this region.",2009 Jun,"['Wang, Jing-Lin', 'Pan, Xiao-Ling', 'Zhang, Hai-Lin', 'Fu, Shi-Hong', 'Wang, Huan-Yu', 'Tang, Qing', 'Wang, Lin-Fa', 'Liang, Guo-Dong']",Emerg Infect Dis,,,True
501a57b3b0e0a5154507b25e23a3f34bf6d2299d,PMC,Interaction of short modified peptides deriving from glycoprotein gp36 of feline immunodeficiency virus with phospholipid membranes,http://dx.doi.org/10.1007/s00249-009-0454-9,PMC2728064,19415263,NO-CC CODE,"A tryptophan-rich octapeptide, C8 (Ac-Trp-Glu-Asp-Trp-Val-Gly-Trp-Ile-NH(2)), modelled on the membrane-proximal external region of the feline immunodeficiency virus (FIV) gp36 glycoprotein ectodomain, exhibits potent antiviral activity against FIV. A mechanism has been proposed by which the peptide, being positioned on the surface of the cell membrane, inhibits its fusion with the virus. In the present work, peptide–lipid interactions of C8 with dimyristoyl phosphatidylcholine liposomes are investigated using electron spin resonance spectroscopy of spin-labelled lipids. Three other peptides, obtained from modifications of C8, have also been investigated, in an attempt to clarify the essential molecular features of the interactions involving the tryptophan residues. The results show that C8 adsorbs strongly on the bilayer surface. Membrane binding requires not only the presence of the Trp residues in the sequence, but also their common orientation on one side of the peptide that is engendered by the WX(2) WX(2) W motif. Membrane interaction correlates closely with peptide antiviral activity, indicating that the membrane is essential in stabilizing the peptide conformation that will be able to inhibit viral infection.",2009 Sep 5,"['D’Errico, Gerardino', 'Vitiello, Giuseppe', 'D’Ursi, Anna Maria', 'Marsh, Derek']",Eur Biophys J,,,True
98e85066186167e53509cadef5d5389f2087da2e,PMC,Mesodynamics in the SARS nucleocapsid measured by NMR field cycling,http://dx.doi.org/10.1007/s10858-009-9347-6,PMC2728245,19641854,NO-CC CODE,"Protein motions on all timescales faster than molecular tumbling are encoded in the spectral density. The dissection of complex protein dynamics is typically performed using relaxation rates determined at high and ultra-high field. Here we expand this range of the spectral density to low fields through field cycling using the nucleocapsid protein of the SARS coronavirus as a model system. The field-cycling approach enables site-specific measurements of R(1) at low fields with the sensitivity and resolution of a high-field magnet. These data, together with high-field relaxation and heteronuclear NOE, provide evidence for correlated rigid-body motions of the entire β-hairpin, and corresponding motions of adjacent loops with a time constant of 0.8 ns (mesodynamics). MD simulations substantiate these findings and provide direct verification of the time scale and collective nature of these motions.",2009 Sep 30,"['Clarkson, Michael W.', 'Lei, Ming', 'Eisenmesser, Elan Z.', 'Labeikovsky, Wladimir', 'Redfield, Alfred', 'Kern, Dorothee']",J Biomol NMR,,,True
b27455411400dcb41fbfb8df4cd9a0976e352426,PMC,Nature of the Virus Associated with Endemic Balkan Nephropathy,http://dx.doi.org/10.3201/eid0808.020042,PMC2732507,12141978,NO-CC CODE,,2002 Aug,"['Riquelme, Cristina', 'Escors, David', 'Ortego, Javier', 'Sanchez, Carlos M.', 'Uzelac-Keserovic, Branislava', 'Apostolov, Konstantin', 'Enjuanes, Luis']",Emerg Infect Dis,,,True
01363927a2d74245f78e5850a085caf62836f9b8,PMC,Respirator Donning in Post-Hurricane New Orleans,http://dx.doi.org/10.3201/eid1305.061490,PMC2738466,17553247,NO-CC CODE,"We evaluated correctness of N95 filtering facepiece respirator donning by the public in post-hurricane New Orleans, where respirators were recommended for mold remediation. We randomly selected, interviewed, and observed 538 participants, using multiple logistic regression for analysis. Only 129 (24%) participants demonstrated proper donning. Errors included nose clip not tightened (71%) and straps incorrectly placed (52%); 22% put on the respirator upside down. Factors independently associated with proper donning were as follows: ever having used a mask or respirator (odds ratio [OR] 5.28; 95% confidence interval [CI], 1.79–22.64); ever having had a respirator fit test (OR 4.40; 95% CI, 2.52–7.81); being male (OR 2.44; 95% CI, 1.50–4.03); Caucasian race (OR 2.09; 95% CI, 1.32–3.33); having a certified respirator (OR 1.99, 95% CI 1.20–3.28); and having participated in mold clean-up (OR 1.82; 95% CI,1.00–3.41). Interventions to improve respirator donning should be considered in planning for influenza epidemics and disasters.",2007 May,"['Cummings, Kristin J.', 'Cox-Ganser, Jean', 'Riggs, Margaret A.', 'Edwards, Nicole', 'Kreiss, Kathleen']",Emerg Infect Dis,,,True
aa71e82c7e8fb18305287a5bccd724d35d238db6,PMC,Dengue Hemorrhagic Fever in Infants: Research Opportunities Ignored,http://dx.doi.org/10.3201/eid0812.020170,PMC2738509,12498666,NO-CC CODE,"The age distribution of cases of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) in infants under the age of 1 year are reported from Bangkok, Thailand, and for the first time for Ho Chi Minh City, Vietnam; Yangon, Myanmar; and Surabaya, Indonesia. The four dengue viruses were isolated from Thai infants, all of whom were having a primary dengue infection. Progress studying the immunologically distinct infant DHF/DSS has been limited; most contemporary research has centered on DHF/DSS accompanying secondary dengue infections. In designing research results obtained in studies on a congruent animal model, feline infectious peritonitis virus (FIPV) infections of kittens born to FIPV-immune queens should be considered. Research challenges presented by infant DHF/DSS are discussed.",2002 Dec,"['Halstead, Scott B.', 'Lan, Nguyen Trong', 'Myint, Thein Thein', 'Shwe, Than Nu', 'Nisalak, Ananda', 'Kalyanarooj, Siripen', 'Nimmannitya, Suchitra', 'Soegijanto, Soegeng', 'Vaughn, David W.', 'Endy, Timothy P.']",Emerg Infect Dis,,,True
2a342bddeca93a319539fa01061776543e38a88f,PMC,Genetically Diverse Coronaviruses in Wild Bird Populations of Northern England,http://dx.doi.org/10.3201/eid1507.090067,PMC2744231,19624927,NO-CC CODE,Infectious bronchitis virus (IBV) causes a costly respiratory viral disease of chickens. The role of wild birds in the epidemiology of IBV is poorly understood. We detected diverse coronaviruses by PCR in wildfowl and wading birds in England. Sequence analysis showed some viruses to be related to IBV.,2009 Jul,"['Hughes, Laura A.', 'Savage, Carol', 'Naylor, Clive', 'Bennett, Malcolm', 'Chantrey, Julian', 'Jones, Richard']",Emerg Infect Dis,,,True
c7cb43c8bc34a2bf0c4a4fcc68525880e194a781,PMC,Emerging Infections in Asia,http://dx.doi.org/10.3201/eid1507.090450,PMC2744235,,NO-CC CODE,,2009 Jul,"Horby, Peter",Emerg Infect Dis,,,False
b411919ba9575cf0fb503965275a640a116edfb0,PMC,Increased Host Species Diversity and Decreased Prevalence of Sin Nombre Virus,http://dx.doi.org/10.3201/eid1507.081083,PMC2744248,19624913,NO-CC CODE,"Emerging outbreaks of zoonotic diseases are affecting humans at an alarming rate. Until the ecological factors associated with zoonoses are better understood, disease emergence will continue. For Lyme disease, disease suppression has been demonstrated by a dilution effect, whereby increasing species diversity decreases disease prevalence in host populations. To test the dilution effect in another disease, we examined 17 ecological variables associated with prevalence of the directly transmitted Sin Nombre virus (genus Hantavirus, etiologic agent of hantavirus pulmonary syndrome) in its wildlife host, the deer mouse (Peromyscus maniculatus). Only species diversity was statistically linked to infection prevalence: as species diversity decreased, infection prevalence increased. The increase was moderate, but prevalence increased exponentially at low levels of diversity, a phenomenon described as zoonotic release. The results suggest that species diversity affects disease emergence.",2009 Jul,"['Dizney, Laurie J.', 'Ruedas, Luis A.']",Emerg Infect Dis,,,True
6fb5908423137fe666c68038150e783398bd50f8,PMC,"Chinese-like Strain of Porcine Epidemic Diarrhea Virus, Thailand",http://dx.doi.org/10.3201/eid1507.081256,PMC2744260,19624933,NO-CC CODE,"Since late 2007, several outbreaks of porcine epidemic diarrhea virus (PEDV) infection have emerged in Thailand. Phylogenetic analysis places all Thai PEDV isolates during the outbreaks in the same clade as the Chinese strain JS-2004-2. This new genotype PEDV is prevailing and currently causing sporadic outbreaks in Thailand.",2009 Jul,"['Puranaveja, Suphasawatt', 'Poolperm, Pariwat', 'Lertwatcharasarakul, Preeda', 'Kesdaengsakonwut, Sawang', 'Boonsoongnern, Alongkot', 'Urairong, Kitcha', 'Kitikoon, Pravina', 'Choojai, Porjit', 'Kedkovid, Roongtham', 'Teankum, Komkrich', 'Thanawongnuwech, Roongroje']",Emerg Infect Dis,,,True
f553255dcfe8027bcf53bcb1147a0f8e1ccbe74b,PMC,Ducks: The “Trojan Horses” of H5N1 influenza,http://dx.doi.org/10.1111/j.1750-2659.2009.00084.x,PMC2749972,19627369,NO-CC CODE,"Abstract Wild ducks are the main reservoir of influenza A viruses that can be transmitted to domestic poultry and mammals, including humans. Of the 16 hemagglutinin (HA) subtypes of influenza A viruses, only the H5 and H7 subtypes cause highly pathogenic (HP) influenza in the natural hosts. Several duck species are naturally resistant to HP Asian H5N1 influenza viruses. These duck species can shed and spread virus from both the respiratory and intestinal tracts while showing few or no disease signs. While the HP Asian H5N1 viruses are 100% lethal for chickens and other gallinaceous poultry, the absence of disease signs in some duck species has led to the concept that ducks are the “Trojan horses” of H5N1 in their surreptitious spread of virus. An important unresolved issue is whether the HP H5N1 viruses are maintained in the wild duck population of the world. Here, we review the ecology and pathobiology of ducks infected with influenza A viruses and ducks’ role in the maintenance and spread of HP H5N1 viruses. We also identify the key questions about the role of ducks that must be resolved in order to understand the emergence and control of pandemic influenza. It is generally accepted that wild duck species can spread HP H5N1 viruses, but there is insufficient evidence to show that ducks maintain these viruses and transfer them from one generation to the next.",2009 Jul 31,"['Kim, Jeong‐Ki', 'Negovetich, Nicholas J.', 'Forrest, Heather L.', 'Webster, Robert G.']",Influenza Other Respir Viruses,,,True
8c74c670f9001e13f725a59a04e19b7c07005d39,PMC,Extraction and characterization of the rhesus macaque T cell receptor β-chain genes,http://dx.doi.org/10.1038/icb.2009.38,PMC2756323,19506572,NO-CC CODE,"Rhesus macaque models have been instrumental for the development and testing of vaccines prior to human studies and have provided fundamental insights into the determinants of immune efficacy in a variety of infectious diseases. However, the characterization of antigen-specific T cell receptor (TCR) repertoires during adaptive immune responses in these models has previously relied on human TCR gene assignments. Here, we extracted and characterized TCR β-chain (TRB) genes from the recently sequenced rhesus macaque genome that are homologous to the human TRB genes. Comparison of the rhesus macaque TRB genes with the human TRB genes revealed an average best-match similarity of 92.9%. Furthermore, we confirmed the usage of most rhesus macaque TRB genes by expressed TCRβ sequences within epitope-specific TCR repertoires. This primary description of the rhesus macaque TRB genes will provide a standardized nomenclature and enable better characterization of TCR usage in studies that utilize this species.",2009 Oct 9,"['Greenaway, Hui Yee', 'Kurniawan, Monica', 'Price, David A', 'Douek, Daniel C', 'Davenport, Miles P', 'Venturi, Vanessa']",Immunol Cell Biol,,,True
65cee74b7f13fb05b462b6814d4eca274a9eb68a,PMC,Extraction and characterization of the rhesus macaque T cell receptor β-chain genes,http://dx.doi.org/10.1038/icb.2009.38,PMC2756323,19506572,NO-CC CODE,"Rhesus macaque models have been instrumental for the development and testing of vaccines prior to human studies and have provided fundamental insights into the determinants of immune efficacy in a variety of infectious diseases. However, the characterization of antigen-specific T cell receptor (TCR) repertoires during adaptive immune responses in these models has previously relied on human TCR gene assignments. Here, we extracted and characterized TCR β-chain (TRB) genes from the recently sequenced rhesus macaque genome that are homologous to the human TRB genes. Comparison of the rhesus macaque TRB genes with the human TRB genes revealed an average best-match similarity of 92.9%. Furthermore, we confirmed the usage of most rhesus macaque TRB genes by expressed TCRβ sequences within epitope-specific TCR repertoires. This primary description of the rhesus macaque TRB genes will provide a standardized nomenclature and enable better characterization of TCR usage in studies that utilize this species.",2009 Oct 9,"['Greenaway, Hui Yee', 'Kurniawan, Monica', 'Price, David A', 'Douek, Daniel C', 'Davenport, Miles P', 'Venturi, Vanessa']",Immunol Cell Biol,,,False
226afecf9d1d5dabbbf7f6b0e3ae0d114ecff299,PMC,Primary biliary cirrhosis,http://dx.doi.org/10.1007/s00281-009-0164-5,PMC2758170,19603170,NO-CC CODE,"Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9–10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13–15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC.",2009 Sep 15,"['Hohenester, Simon', 'Oude-Elferink, Ronald P. J.', 'Beuers, Ulrich']",Semin Immunopathol,,,True
ae453f1b3f495c4cea808f1ab92de2c7fb80b72d,PMC,Impairment of germline transmission after blastocyst injection with murine embryonic stem cells cultured with mouse hepatitis virus and mouse minute virus,http://dx.doi.org/10.1007/s11248-008-9216-1,PMC2758372,18800235,NO-CC CODE,"The aim of this study was to determine the susceptibility of murine embryonic stem (mESCs) to mouse hepatitis virus (MHV-A59) and mouse minute virus (MMVp) and the effect of these viruses on germline transmission (GLT) and the serological status of recipients and pups. When recipients received 10 blastocysts, each injected with 10(0) TCID(50) MHV-A59, three out of five recipients and four out of 14 pups from three litters became seropositive. When blastocysts were injected with 10(−5) TCID(50) MMVp, all four recipients and 14 pups from four litters remained seronegative. The mESCs replicated MHV-A59 but not MMVp, MHV-A59 being cytolytic for mESCs. Exposure of mESCs to the viruses over four to five passages but not for 6 h affected GLT. Recipients were seropositive for MHV-A59 but not for MMVp when mESCs were cultured with the virus over four or five passages. The data show that GLT is affected by virus-contaminated mESCs.",2009 Feb 18,"['Mahabir, E.', 'Reindl, K.', 'Mysliwietz, J.', 'Needham, J.', 'Bulian, D.', 'Markoullis, K.', 'Scherb, H.', 'Schmidt, J.']",Transgenic Res,,,True
9f2eacde02bfd34993a2eab9d87c2643fcfd17e2,PMC,Cytokine Profiles in Human Immunodeficiency Virus-Infected Children Treated With Highly Active Antiretroviral Therapy,http://dx.doi.org/10.1186/1758-2652-7-2-71,PMC2759641,19825129,NO-CC CODE,"CONTEXT: There have been few longitudinal studies of cytokine production in neonatally acquired HIV-1 infection and none in Asian or Chinese children. OBJECTIVE: To determine whether monitoring cytokine production could contribute to the better management of pediatric patients with HIV-1 infection. SETTING: Clinical Immunology Laboratory and Pediatrics Department, University Hospital, Hong Kong. PATIENTS: Ten Asian and 2 Eurasian children infected with HIV-1 by mother-to-child transmission were followed for up to 5 years while on treatment with highly active antiretroviral therapy (HAART). MAIN OUTCOME MEASURES: Numbers of unstimulated and mitogen-activated cytokine-secreting cells (IFN-gamma, interleukin [IL]-2, IL-4, IL-6, IL-10, IL-12, and TNF-alpha) were measured by ELISPOT assay at frequent intervals, and correlations were sought with CD4+ and CD8+ cell counts and viral loads. RESULTS: Mitogen-stimulated IL-2-secreting cells were directly associated with recovery of CD4+ cells. Correlations with viral load were found for Con A-induced IFN-gamma, Con A-induced IL-4, and unstimulated IL-10, suggesting that these cytokines were either suppressed by high virus levels or that higher cytokine levels suppressed virus. IFN-gamma, IL-2-, IL-4-, and IL-12-secreting cells induced by PHA, Con A, and/or SAC tended to increase for the first 3-4 years of treatment but declined thereafter. CONCLUSION: Alterations in cytokine profiles were not associated with adverse clinical events and there was little evidence to indicate that monitoring cytokine enzyme-linked immunospots (ELISPOTs) could contribute to pediatric patient management.",2005 May 3,"['Jones, Brian M', 'Chiu, Susan SS', 'Wong, Wilfred HS', 'Lim, Wilina WL', 'Lau, Yu-lung']",J Int AIDS Soc,,,True
dc91750f913c083da70bb7dd1816c0418eaf346d,PMC,"Analysis of trends in emergency department attendances, hospital admissions and medical staffing in a Hong Kong university hospital: 5-year study",http://dx.doi.org/10.1007/s12245-009-0098-7,PMC2760706,20157463,NO-CC CODE,"BACKGROUND: The workload of emergency departments (ED) continually changes in response to presentations, overcrowding and availability of expertise and investigations. AIMS: To investigate changes in ED presentations and care processes, and the relationship of patient demand and ED staff resources to waiting times and processing times. METHODS: Retrospective analysis of prospectively collected administrative data from January 1999 to April 2005 in an emergency department in a university teaching hospital in Hong Kong. All patients attending the emergency department during the study period were included. Monthly attendance data were retrieved and analysed to determine both qualitative and quantitative changes in the patterns of presentation to the ED using prospectively gathered data. RESULTS: Total ED attendances decreased by 25% during the study with little seasonal variation. The admission rate and the use of ambulances increased steadily and significantly. Medical patients are increasing proportionately, but trauma patients are decreased in number. CONCLUSION: There have been major changes in the patterns of ED attendances and ED waiting times over the study period in this teaching hospital ED. Decreasing overall ED numbers are offset by an increasingly elderly population and a more complex case mix. Reducing clinical staff numbers appears to reduce the ED’s capacity to provide timely assessments and care and to function as hospital gatekeepers. Restoring staff numbers to previous levels may improve the quality and timeliness of ED services. It is necessary to refine measures of ED complexity and workload to determine appropriate staffing levels in the future.",2009 Apr 8,"['Wai, Abraham K. C.', 'Chor, C. M.', 'Lee, Allen T. C.', 'Sittambunka, Yuwares', 'Graham, Colin A.', 'Rainer, Timothy H.']",Int J Emerg Med,,,True
3f01702c71fa172be560638b826441239c956227,PMC,T10B9 monoclonal antibody: A short-acting nonstimulating monoclonal antibody that spares γδ T-cells and treats and prevents cellular rejection,,PMC2769243,19920935,NO-CC CODE,"T10B9.1A-31/MEDI-500 is a nonmitogenic immunoglobulin M kappa murine monoclonal antibody (mAb) directed against the alpha-beta (αβ) heterodimer of the T-lymphocyte receptor complex. The hybridoma was first produced by fusing spleen cells from BALB/C mice immunized with human peripheral blood T-lymphocytes with SP2/O-Ag14 mutant myeloma cells. The mAb is produced and purified using multistep ion exchange and molecular sieve chromatography protocols. T10B9 has been used successfully to treat acute cellular rejection in renal transplantation and as an immunosuppression induction agent in heart and simultaneous kidney-pancreas transplantation. Because T10B9 is nonmitogenic and causes minimal cytokine release, both treatment of rejection and induction of immunosuppression were accomplished with significantly fewer and milder untoward effects (cytokine release syndrome) than its comparator OKT3. Since T10B9 is directed against the αβ heterodimer of the CD3 epitope, it spares the gamma delta (γδ) region. These gamma delta (γδ) T cells have a unique role in the immune response controlling many serious human diseases and perhaps facilitating the development of immunologic tolerance. T10B9 has a relatively short duration of action, depleting T cells for only 10 to 14 days, unlike the protracted depletion seen with thymoglobulin and Campath-1H. There is no B-lymphocyte depletion with T10B9 as there is with both of the aforementioned reagents. The lack of prolonged lymphocyte depletion may account for less infection observed with T10B9 treatment.",2009 Sep 21,"['Waid, Thomas H', 'Thompson, John S', 'Siemionow, Maria', 'Brown, Stephen A']",Drug Des Devel Ther,,,True
b8d17f3628650e4b6ab0d9068e9e25aa26857569,PMC,"All-Cause Mortality in Tianjin, China, 1999-2004",,PMC2774646,19755008,NO-CC CODE,"INTRODUCTION: We analyzed trends of major causes of death in Tianjin, China, from 1999 through 2004 to better inform disease prevention and control programs and policies. METHODS: To report all-cause deaths among Tianjin residents from 1999 through 2004, we standardized mortality rates to the world population in 2000. We analyzed age, sex, and geographic distribution of deaths from different causes and the leading causes of death in Tianjin. RESULTS: The 5 leading causes of death in Tianjin were cardiovascular disease, cerebrovascular disease, malignant neoplasm, chronic lower respiratory disease, and injuries and poisoning. Mortality in Tianjin declined from 0.60% in 1999 to 0.48% in 2004. Noncommunicable diseases accounted for more than 80% of all deaths. Infant and maternal mortality in Tianjin were low. Life expectancy of Tianjin residents increased every year but was consistently longer in women. When deaths from the main chronic diseases are not considered, life expectancy lengthens substantially. CONCLUSION: Chronic diseases are the leading cause of death in Tianjin, China. China should commit additional resources to supporting chronic disease prevention and control programs, including proven special health promotion projects.",2009 Sep 15,"['Wang, Xiexiu', 'Jiang, Guohong', 'Wang, Dezheng', 'Pan, Yi', 'Boulton, Matthew']",Prev Chronic Dis,,,True
92a874a4d2371061665a018eee85abf9e857ebc2,PMC,Integrated Blood Barcode Chips,http://dx.doi.org/10.1038/nbt.1507,PMC2775523,19029914,NO-CC CODE,"Blood comprises the largest version of the human proteome1. Changes of plasma protein profiles can reflect physiological or pathological conditions associated with many human diseases, making blood the most important fluid for clinical diagnostics2-4. Nevertheless, only a handful of plasma proteins are utilized in routine clinical tests. This is due to a host of reasons, including the intrinsic complexity of the plasma proteome1, the heterogeneity of human diseases and the fast kinetics associated with protein degradation in sampled blood5. Simple technologies that can sensitively sample large numbers of proteins over broad concentration ranges, from small amounts of blood, and within minutes of sample collection, would assist in solving these problems. Herein, we report on an integrated microfluidic system, called the Integrated Blood Barcode Chip (IBBC). It enables on-chip blood separation and the rapid measurement of a panel of plasma proteins from small quantities of blood samples including a fingerprick of whole blood. This platform holds potential for inexpensive, non-invasive, and informative clinical diagnoses, particularly, for point-of-care.",2008 Dec 16,"['Fan, Rong', 'Vermesh, Ophir', 'Srivastava, Alok', 'Yen, Brian K.H.', 'Qin, Lidong', 'Ahmad, Habib', 'Kwong, Gabriel A.', 'Liu, Chao-Chao', 'Gould, Juliane', 'Hood, Leroy', 'Heath, James R.']",Nat Biotechnol,,,True
2cdb7b3be2a0c0e1c276302897afc6d3f4a16ef4,PMC,"The ongoing H1N1 flu pandemic and the intensive care community: challenges, opportunities, and the duties of scientific societies and intensivists",http://dx.doi.org/10.1007/s00134-009-1706-y,PMC2779348,19841893,NO-CC CODE,,2009 Dec 20,"['Moreno, Rui P.', 'Rhodes, Andrew', 'Chiche, Jean-Daniel']",Intensive Care Med,,,True
6939348451319caef5c642925739778b12a41d52,PMC,Model-consistent estimation of the basic reproduction number from the incidence of an emerging infection,http://dx.doi.org/10.1007/s00285-007-0112-8,PMC2782110,17684743,NO-CC CODE,"We investigate the merit of deriving an estimate of the basic reproduction number [Formula: see text] early in an outbreak of an (emerging) infection from estimates of the incidence and generation interval only. We compare such estimates of [Formula: see text] with estimates incorporating additional model assumptions, and determine the circumstances under which the different estimates are consistent. We show that one has to be careful when using observed exponential growth rates to derive an estimate of [Formula: see text] , and we quantify the discrepancies that arise.",2007 Nov 8,"['Roberts, M. G.', 'Heesterbeek, J. A. P.']",J Math Biol,,,True
8ceb037798bd3fa6941261d1b888fe0cb79f2850,PMC,A novel two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein,http://dx.doi.org/10.1038/nsmb.1680,PMC2784181,19838190,NO-CC CODE,"Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression, including type I interferon production, by promoting host mRNA degradation and inhibiting host translation, in infected cells. We present evidence that nsp1 uses a novel, two-pronged strategy to inhibit host translation/gene expression. Nsp1 bound to the 40S ribosomal subunit and inactivated the translational activity of the 40S subunits. Furthermore, the nsp1-40S ribosome complex induced the modification of the 5'-region of capped mRNA template and rendered the template RNA translationally incompetent. Nsp1 also induced RNA cleavage in templates carrying the internal ribosome entry site (IRES) from encephalomyocarditis virus, but not in those carrying IRESs from hepatitis C and cricket paralysis viruses, demonstrating that the nsp1-induced RNA modification was template-dependent. We speculate that the mRNAs that underwent the nsp1-mediated modification are marked for rapid turnover by the host RNA degradation machinery.",2009 Nov 18,"['Kamitani, Wataru', 'Huang, Cheng', 'Narayanan, Krishna', 'Lokugamage, Kumari G.', 'Makino, Shinji']",Nat Struct Mol Biol,,,True
377b501684f6ec4b6c7988f5d3edffadfb24e7ce,PMC,A novel two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein,http://dx.doi.org/10.1038/nsmb.1680,PMC2784181,19838190,NO-CC CODE,"Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression, including type I interferon production, by promoting host mRNA degradation and inhibiting host translation, in infected cells. We present evidence that nsp1 uses a novel, two-pronged strategy to inhibit host translation/gene expression. Nsp1 bound to the 40S ribosomal subunit and inactivated the translational activity of the 40S subunits. Furthermore, the nsp1-40S ribosome complex induced the modification of the 5'-region of capped mRNA template and rendered the template RNA translationally incompetent. Nsp1 also induced RNA cleavage in templates carrying the internal ribosome entry site (IRES) from encephalomyocarditis virus, but not in those carrying IRESs from hepatitis C and cricket paralysis viruses, demonstrating that the nsp1-induced RNA modification was template-dependent. We speculate that the mRNAs that underwent the nsp1-mediated modification are marked for rapid turnover by the host RNA degradation machinery.",2009 Nov 18,"['Kamitani, Wataru', 'Huang, Cheng', 'Narayanan, Krishna', 'Lokugamage, Kumari G.', 'Makino, Shinji']",Nat Struct Mol Biol,,,False
7b329eb91fdc5ea7e947a48e414a7a1f10ed40c9,PMC,Exposure of cats to low doses of FeLV: seroconversion as the sole parameter of infection,http://dx.doi.org/10.1051/vetres/2009065,PMC2789331,19861115,NO-CC CODE,"In felids, feline leukemia virus (FeLV) infection results in a variety of outcomes that range from abortive (virus readily eliminated and never detectable) to progressive infection (persistent viremia and viral shedding). Recently, a novel outcome was postulated for low FeLV infectious doses. Naïve cats exposed to faeces of persistently infected cats seroconverted, indicating infection, but remained negative for provirus and p27 antigen in blood. FeLV provirus was found in some tissues but not in the bone marrow, infection of which is usually considered a necessary stage for disease progression. To investigate the impact of low FeLV doses on young cats and to test the hypothesis that low dose exposure may lead to an unknown pathogenesis of infection without involvement of the bone marrow, 21 cats were infected oronasally with variable viral doses. Blood p27, proviral and viral loads were followed until week 20 post-infection. Tissue proviral loads were determined as well. The immune response was monitored by measuring FeLV whole virus and p45 antibodies; and feline oncornavirus-associated cell membrane antigen (FOCMA) assay. One cat showed regressive infection (transient antigenemia, persistent provirus-positivity, and seroconversion) with provirus only found in some organs at sacrifice. In 7 of the 20 remaining cats FOCMA assay positivity was the only sign of infection, while all other tests were negative. Overall, the results show that FeLV low dose exposure can result in seroconversion during a presumed abortive infection. Therefore, commonly used detection methods do not detect all FeLV-infected animals, possibly leading to an underestimation of the prevalence of infection.",2010 Oct 28 Mar-Apr,"['Major, Andrea', 'Cattori, Valentino', 'Boenzli, Eva', 'Riond, Barbara', 'Ossent, Peter', 'Meli, Marina Luisa', 'Hofmann-Lehmann, Regina', 'Lutz, Hans']",Vet Res,,,True
5208adba66fd95d02e5358f74ce0c3a45d502c9d,PMC,"Coronaviruses in Children, Greece",http://dx.doi.org/10.3201/eid1306.061353,PMC2792836,17582904,NO-CC CODE,,2007 Jun,"['Papa, Anna', 'Papadimitriou, Evangelia', 'de Souza Luna, Luciano Kleber', 'Al Masri, Motassim', 'Souliou, Efimia', 'Eboriadou, Maria', 'Antoniadis, Antonis', 'Drosten, Christian']",Emerg Infect Dis,,,True
f5cb9270ebde80bfaf1298576cb7c6fc7076f6b7,PMC,"European Hedgehogs as Hosts for Borrelia spp., Germany",http://dx.doi.org/10.3201/eid1306.070224,PMC2792852,17582907,NO-CC CODE,,2007 Jun,"['Skuballa, Jasmin', 'Oehme, Rainer', 'Hartelt, Kathrin', 'Petney, Trevor', 'Bücher, Thomas', 'Kimmig, Peter', 'Taraschewski, Horst']",Emerg Infect Dis,,,True
56cbccd7c5d62a459ac405ce9c7de45d77ec19df,PMC,Abstracts,http://dx.doi.org/10.1007/s00431-006-0349-z,PMC2799065,17242961,NO-CC CODE,,2006 Nov 20,,Eur J Pediatr,,,False
12627b91b3942f3727458c1bd4653be6fe30600f,PMC,Isolation and identification of a canine coronavirus strain from giant pandas (Ailuropoda melanoleuca),http://dx.doi.org/10.4142/jvs.2009.10.3.261,PMC2801125,19687628,NO-CC CODE,"Two giant pandas (Ailuropoda melanoleuca) died of unknown causes in a Chinese zoo. The clinical disease profile suggested that the pandas may have suffered a viral infection. Therefore, a series of detection including virus isolation, electron microscopy, cytobiological assay, serum neutralization and RT-PCR were used to identify the virus. It was determined that the isolated virus was a canine coronavirus (CCV), on the basis of coronavirus, neutralization by canine anti-CCV serum, and 84.3% to 100% amino acid sequence similarity with CCV. The results suggest that the affected pandas had been infected with CCV.",2009 Sep 8,"['Gao, Feng-Shan', 'Hu, Gui-Xue', 'Xia, Xian-zhu', 'Gao, Yu-Wei', 'Bai, Ya-Duo', 'Zou, Xiao-Huan']",J Vet Sci,,,True
da6cb24186f59847fb1dcdb6614ab15b2bd3377c,PMC,Detection and molecular characterization of infectious bronchitis virus isolated from recent outbreaks in broiler flocks in Thailand,http://dx.doi.org/10.4142/jvs.2009.10.3.219,PMC2801127,19687622,NO-CC CODE,"Thirteen field isolates of infectious bronchitis virus (IBV) were isolated from broiler flocks in Thailand between January and June 2008. The 878-bp of the S1 gene covering a hypervariable region was amplified and sequenced. Phylogenetic analysis based on that region revealed that these viruses were separated into two groups (I and II). IBV isolates in group I were not related to other IBV strains published in the GenBank database. Group 1 nucleotide sequence identities were less than 85% and amino acid sequence identities less than 84% in common with IBVs published in the GenBank database. This group likely represents the strains indigenous to Thailand. The isolates in group II showed a close relationship with Chinese IBVs. They had nucleotide sequence identities of 97-98% and amino acid sequence identities 96-98% in common with Chinese IBVs (strain A2, SH and QXIBV). This finding indicated that the recent Thai IBVs evolved separately and at least two groups of viruses are circulating in Thailand.",2009 Sep 7,"['Pohuang, Tawatchai', 'Chansiripornchai, Niwat', 'Tawatsin, Achara', 'Sasipreeyajan, Jiroj']",J Vet Sci,,,True
b1e9d1c6ab23addf3775583442376e4d5e63e44e,PMC,Definition of Mafa-A and -B haplotypes in pedigreed cynomolgus macaques (Macaca fascicularis),http://dx.doi.org/10.1007/s00251-009-0412-9,PMC2802488,19937015,NO-CC CODE,"The major histocompatibility complex (MHC) class I B gene/allelic repertoire was investigated in a pedigreed population of cynomolgus macaques of mixed Indonesian/Malaysian origin. The Mafa-B alleles detected in this cohort are mostly specific for a given geographic area, and only a small number of alleles appears to be shared with other populations. This suggests the fast evolution of Mafa-B alleles due to adaptation to new environments. In contrast to humans, the B locus in Old World monkeys displays extensive copy number variation. The Mafa-B and previously defined -A gene combinations segregate in families and thus allowed the definition of extended haplotypes. In many cases it was possible to assign a particular Mafa-I allele to one of these Mafa-A/B haplotypes as well. The presence of a large number of stable haplotypes in this cohort of animals, which was pedigreed for up to eight generations, looks promising for developing discriminative MHC typing tools that are less cumbersome. Furthermore, the discovery of 53 unreported Mafa-B sequences expands the lexicon of alleles significantly, and may help in understanding the complex organisation of the macaque B region.",2009 Dec 24,"['Otting, Nel', 'Doxiadis, Gaby G. M.', 'Bontrop, Ronald E.']",Immunogenetics,,,True
dab2d95da5307c840eb4a1e00f0186022541d63d,PMC,"A model of tripeptidyl-peptidase I (CLN2), a ubiquitous and highly conserved member of the sedolisin family of serine-carboxyl peptidases",http://dx.doi.org/10.1186/1472-6807-3-8,PMC280685,14609438,NO-CC CODE,"BACKGROUND: Tripeptidyl-peptidase I, also known as CLN2, is a member of the family of sedolisins (serine-carboxyl peptidases). In humans, defects in expression of this enzyme lead to a fatal neurodegenerative disease, classical late-infantile neuronal ceroid lipofuscinosis. Similar enzymes have been found in the genomic sequences of several species, but neither systematic analyses of their distribution nor modeling of their structures have been previously attempted. RESULTS: We have analyzed the presence of orthologs of human CLN2 in the genomic sequences of a number of eukaryotic species. Enzymes with sequences sharing over 80% identity have been found in the genomes of macaque, mouse, rat, dog, and cow. Closely related, although clearly distinct, enzymes are present in fish (fugu and zebra), as well as in frogs (Xenopus tropicalis). A three-dimensional model of human CLN2 was built based mainly on the homology with Pseudomonas sp. 101 sedolisin. CONCLUSION: CLN2 is very highly conserved and widely distributed among higher organisms and may play an important role in their life cycles. The model presented here indicates a very open and accessible active site that is almost completely conserved among all known CLN2 enzymes. This result is somehow surprising for a tripeptidase where the presence of a more constrained binding pocket was anticipated. This structural model should be useful in the search for the physiological substrates of these enzymes and in the design of more specific inhibitors of CLN2.",2003 Nov 11,"['Wlodawer, Alexander', 'Durell, Stewart R', 'Li, Mi', 'Oyama, Hiroshi', 'Oda, Kohei', 'Dunn, Ben M']",BMC Struct Biol,,,True
32c8722461407f64b15ce12595cd8eb7cbe3733c,PMC,Pathogenicity and antigenicity of a new variant of Korean nephropathogenic infectious bronchitis virus,http://dx.doi.org/10.4142/jvs.2009.10.4.357,PMC2807275,19934604,NO-CC CODE,"Despite the existence of an active vaccination program, recently emerged strains of nephropathogenic infectious bronchitis virus (IBV) in Korea have caused significant economic losses in the poultry industry. In this study, we assessed the pathogenic and antigenic characteristics of a K-IIb type field strain of IBV that emerged in Korea since 2003, such as Kr/Q43/06. Specific pathogen free 1-week-old chickens exhibited severe respiratory symptoms (dyspnea) and nephropathogenic lesions (swollen kidneys with nephritis and urate deposits) following challenge with the recent IBV field strain. The antigenic relatedness (R value), based on a calculated virus neutralization index, of the K-IIb type field strain and K-IIa type strain KM91 (isolated in 1991) was 30%, which indicated that the recent strain, Kr/Q43/06, is a new variant that is antigenically distinct from strain KM91. This report is the first to document the emergence of a new antigenic variant of nephropathogenic IBV in chicken from Korea.",2009 Dec 26,"['Choi, Kang-Seuk', 'Lee, Eun-Kyoung', 'Jeon, Woo-Jin', 'Park, Mi-Ja', 'Kim, Jin-Won', 'Kwon, Jun-Hun']",J Vet Sci,,,True
748ef951c31564eb3eb37a7bc947ce5ff4cb5fdd,PMC,Fluorescence Competition Assay Measurements of Free Energy Changes for RNA Pseudoknots,http://dx.doi.org/10.1021/bi901541j,PMC2808147,19921809,NO-CC CODE,"[Image: see text] RNA pseudoknots have important functions, and thermodynamic stability is a key to predicting pseudoknots in RNA sequences and to understanding their functions. Traditional methods, such as UV melting and differential scanning calorimetry, for measuring RNA thermodynamics are restricted to temperature ranges around the melting temperature for a pseudoknot. Here, we report RNA pseudoknot free energy changes at 37 °C measured by fluorescence competition assays. Sequence-dependent studies for the loop 1−stem 2 region reveal (1) the individual nearest-neighbor hydrogen bonding (INN-HB) model provides a reasonable estimate for the free energy change when a Watson−Crick base pair in stem 2 is changed, (2) the loop entropy can be estimated by a statistical polymer model, although some penalty for certain loop sequences is necessary, and (3) tertiary interactions can significantly stabilize pseudoknots and extending the length of stem 2 may alter tertiary interactions such that the INN-HB model does not predict the net effect of adding a base pair. The results can inform writing of algorithms for predicting and/or designing RNA secondary structures.",2010 Jan 26,"['Liu, Biao', 'Shankar, Neelaabh', 'Turner, Douglas H.']",Biochemistry,,,True
539c8819307bd03a90bfd559f47d4c82e7aab58d,PMC,Fluorescence Competition Assay Measurements of Free Energy Changes for RNA Pseudoknots,http://dx.doi.org/10.1021/bi901541j,PMC2808147,19921809,NO-CC CODE,"[Image: see text] RNA pseudoknots have important functions, and thermodynamic stability is a key to predicting pseudoknots in RNA sequences and to understanding their functions. Traditional methods, such as UV melting and differential scanning calorimetry, for measuring RNA thermodynamics are restricted to temperature ranges around the melting temperature for a pseudoknot. Here, we report RNA pseudoknot free energy changes at 37 °C measured by fluorescence competition assays. Sequence-dependent studies for the loop 1−stem 2 region reveal (1) the individual nearest-neighbor hydrogen bonding (INN-HB) model provides a reasonable estimate for the free energy change when a Watson−Crick base pair in stem 2 is changed, (2) the loop entropy can be estimated by a statistical polymer model, although some penalty for certain loop sequences is necessary, and (3) tertiary interactions can significantly stabilize pseudoknots and extending the length of stem 2 may alter tertiary interactions such that the INN-HB model does not predict the net effect of adding a base pair. The results can inform writing of algorithms for predicting and/or designing RNA secondary structures.",2010 Jan 26,"['Liu, Biao', 'Shankar, Neelaabh', 'Turner, Douglas H.']",Biochemistry,,,True
f3a7c66f75eba81e19ad7e1e05aa8ae1133a984c,PMC,Human genomics and preparedness for infectious threats,http://dx.doi.org/10.1186/gm119,PMC2808735,20090897,NO-CC CODE,"Public health preparedness requires effective surveillance of and rapid response to infectious disease outbreaks. Inclusion of research activities within the outbreak setting provides important opportunities to maximize limited resources, to enhance gains in scientific knowledge, and ultimately to increase levels of preparedness. With rapid advances in laboratory technologies, banking and analysis of human genomic specimens can be conducted as part of public health investigations, enabling valuable research well into the future.",2009 Dec 29,"['Dowling, Nicole F', 'Gwinn, Marta', 'Mawle, Alison']",Genome Med,,,True
63188fe828f332759eb902e48628239cb4679964,PMC,"Use of Revised International Health Regulations during Influenza A (H1N1) Epidemic, 2009",http://dx.doi.org/10.3201/eid1508.090665,PMC2815989,19751576,NO-CC CODE,"Strong international health agreements and good planning created a structure and common procedure for nations involved in detection and evaluation of the emergence of influenza A (H1N1). This report describes a timeline of events that led to the determination of the epidemic as a public health emergency of international concern, following the agreed-upon procedures of the International Health Regulations. These events illustrate the need for sound international health agreements and should be a call to action for all nations to implement these agreements to the best of their abilities.",2009 Aug,"Katz, Rebecca",Emerg Infect Dis,,,True
874c67489633255b8ea0b0412f5a9261f5de31cf,PMC,"Distant Relatives of Severe Acute Respiratory Syndrome Coronavirus and Close Relatives of Human Coronavirus 229E in Bats, Ghana",http://dx.doi.org/10.3201/eid1509.090224,PMC2819850,19788804,NO-CC CODE,"We tested 12 bat species in Ghana for coronavirus (CoV) RNA. The virus prevalence in insectivorous bats (n = 123) was 9.76%. CoV was not detected in 212 fecal samples from Eidolon helvum fruit bats. Leaf-nosed bats pertaining to Hipposideros ruber by morphology had group 1 and group 2 CoVs. Virus concentrations were <45,000 copies/100 mg of bat feces. The diversified group 1 CoV shared a common ancestor with the human common cold virus hCoV-229E but not with hCoV-NL63, disputing hypotheses of common human descent. The most recent common ancestor of hCoV-229E and GhanaBt-CoVGrp1 existed in ≈1686–1800 ad. The GhanaBt-CoVGrp2 shared an old ancestor (≈2,400 years) with the severe acute respiratory syndrome–like group of CoV.",2009 Sep,"['Pfefferle, Susanne', 'Oppong, Samuel', 'Drexler, Jan Felix', 'Gloza-Rausch, Florian', 'Ipsen, Anne', 'Seebens, Antje', 'Müller, Marcel A.', 'Annan, Augustina', 'Vallo, Peter', 'Adu-Sarkodie, Yaw', 'Kruppa, Thomas F.', 'Drosten, Christian']",Emerg Infect Dis,,,True
51fef2a2c2978a6384b1925376b460da142708ad,PMC,"Clinical and Epidemiologic Characteristics of 3 Early Cases of Influenza A Pandemic (H1N1) 2009 Virus Infection, People’s Republic of China, 2009",http://dx.doi.org/10.3201/eid1509.090794,PMC2819857,19788809,NO-CC CODE,"On May 7, 2009, a national network was organized in the People’s Republic of China for the surveillance, reporting, diagnosis, and treatment of influenza A pandemic (H1N1) 2009 virus infection (pandemic [H1N1] 2009). Persons with suspected cases are required to report to the Chinese Center for Disease Control and Prevention and the Ministry of Health within 24 hours; the patient’s close contacts are then traced and placed in quarantine for 7 days. We report 3 confirmed early cases of pandemic (H1N1) 2009. Two cases were imported from United States; the other was imported from Canada. The patients exhibited fever and signs and other symptoms that were indistinguishable from those of seasonal influenza. Serial virologic monitoring of pharyngeal swabs showed that they were negative for pandemic (H1N1) 2009 virus by real-time reverse transcription–PCR 4–6 days after onset of illness. One close contact whose sample tested positive for pandemic (H1N1) 2009 virus had no symptoms during quarantine. A national network is essential for controlling pandemic (H1N1) 2009.",2009 Sep,"['Bin, Cao', 'Xingwang, Li', 'Yuelong, Shu', 'Nan, Jiang', 'Shijun, Chen', 'Xiayuan, Xu', 'Chen, Wang', None]",Emerg Infect Dis,,,True
c5d0bce44486081ea768a33f90828d3ef996af07,PMC,Using Satellite Images of Environmental Changes to Predict Infectious Disease Outbreaks,http://dx.doi.org/10.3201/eid/1509.081334,PMC2819876,19788799,NO-CC CODE,"Recent events clearly illustrate a continued vulnerability of large populations to infectious diseases, which is related to our changing human-constructed and natural environments. A single person with multidrug-resistant tuberculosis in 2007 provided a wake-up call to the United States and global public health infrastructure, as the health professionals and the public realized that today’s ease of airline travel can potentially expose hundreds of persons to an untreatable disease associated with an infectious agent. Ease of travel, population increase, population displacement, pollution, agricultural activity, changing socioeconomic structures, and international conflicts worldwide have each contributed to infectious disease events. Today, however, nothing is larger in scale, has more potential for long-term effects, and is more uncertain than the effects of climate change on infectious disease outbreaks, epidemics, and pandemics. We discuss advances in our ability to predict these events and, in particular, the critical role that satellite imaging could play in mounting an effective response.",2009 Sep,"['Ford, Timothy E.', 'Colwell, Rita R.', 'Rose, Joan B.', 'Morse, Stephen S.', 'Rogers, David J.', 'Yates, Terry L.']",Emerg Infect Dis,,,True
665921bbd601a833446d193381861aa1275cb5ee,PMC,Genetics and Pathogenesis of Feline Infectious Peritonitis Virus,http://dx.doi.org/10.3201/eid1509.081573,PMC2819880,19788813,NO-CC CODE,"Feline coronavirus (FCoV) is endemic in feral cat populations and cat colonies, frequently preceding outbreaks of fatal feline infectious peritonitis (FIP). FCoV exhibits 2 biotypes: the pathogenic disease and a benign infection with feline enteric coronavirus (FECV). Uncertainty remains regarding whether genetically distinctive avirulent and virulent forms coexist or whether an avirulent form mutates in vivo, causing FIP. To resolve these alternative hypotheses, we isolated viral sequences from FCoV-infected clinically healthy and sick cats (8 FIP cases and 48 FECV-asymptomatic animals); 735 sequences from 4 gene segments were generated and subjected to phylogenetic analyses. Viral sequences from healthy cats were distinct from sick cats on the basis of genetic distances observed in the membrane and nonstructural protein 7b genes. These data demonstrate distinctive circulating virulent and avirulent strains in natural populations. In addition, 5 membrane protein amino acid residues with functional potential differentiated healthy cats from cats with FIP. These findings may have potential as diagnostic markers for virulent FIP-associated FCoV.",2009 Sep,"['Brown, Meredith A.', 'Troyer, Jennifer L.', 'Pecon-Slattery, Jill', 'Roelke, Melody E.', 'O’Brien, Stephen J.']",Emerg Infect Dis,,,False
4fa21ce9a36501d674d0e98146b3233a7e2bc4d6,PMC,Genetics and Pathogenesis of Feline Infectious Peritonitis Virus,http://dx.doi.org/10.3201/eid1509.081573,PMC2819880,19788813,NO-CC CODE,"Feline coronavirus (FCoV) is endemic in feral cat populations and cat colonies, frequently preceding outbreaks of fatal feline infectious peritonitis (FIP). FCoV exhibits 2 biotypes: the pathogenic disease and a benign infection with feline enteric coronavirus (FECV). Uncertainty remains regarding whether genetically distinctive avirulent and virulent forms coexist or whether an avirulent form mutates in vivo, causing FIP. To resolve these alternative hypotheses, we isolated viral sequences from FCoV-infected clinically healthy and sick cats (8 FIP cases and 48 FECV-asymptomatic animals); 735 sequences from 4 gene segments were generated and subjected to phylogenetic analyses. Viral sequences from healthy cats were distinct from sick cats on the basis of genetic distances observed in the membrane and nonstructural protein 7b genes. These data demonstrate distinctive circulating virulent and avirulent strains in natural populations. In addition, 5 membrane protein amino acid residues with functional potential differentiated healthy cats from cats with FIP. These findings may have potential as diagnostic markers for virulent FIP-associated FCoV.",2009 Sep,"['Brown, Meredith A.', 'Troyer, Jennifer L.', 'Pecon-Slattery, Jill', 'Roelke, Melody E.', 'O’Brien, Stephen J.']",Emerg Infect Dis,,,False
07287765df0556a744dd888dc6585bc1d4da6dc9,PMC,Genetics and Pathogenesis of Feline Infectious Peritonitis Virus,http://dx.doi.org/10.3201/eid1509.081573,PMC2819880,19788813,NO-CC CODE,"Feline coronavirus (FCoV) is endemic in feral cat populations and cat colonies, frequently preceding outbreaks of fatal feline infectious peritonitis (FIP). FCoV exhibits 2 biotypes: the pathogenic disease and a benign infection with feline enteric coronavirus (FECV). Uncertainty remains regarding whether genetically distinctive avirulent and virulent forms coexist or whether an avirulent form mutates in vivo, causing FIP. To resolve these alternative hypotheses, we isolated viral sequences from FCoV-infected clinically healthy and sick cats (8 FIP cases and 48 FECV-asymptomatic animals); 735 sequences from 4 gene segments were generated and subjected to phylogenetic analyses. Viral sequences from healthy cats were distinct from sick cats on the basis of genetic distances observed in the membrane and nonstructural protein 7b genes. These data demonstrate distinctive circulating virulent and avirulent strains in natural populations. In addition, 5 membrane protein amino acid residues with functional potential differentiated healthy cats from cats with FIP. These findings may have potential as diagnostic markers for virulent FIP-associated FCoV.",2009 Sep,"['Brown, Meredith A.', 'Troyer, Jennifer L.', 'Pecon-Slattery, Jill', 'Roelke, Melody E.', 'O’Brien, Stephen J.']",Emerg Infect Dis,,,False
9ba8b44bb13969b76e138f9593a787943c0ad9e9,PMC,Genetics and Pathogenesis of Feline Infectious Peritonitis Virus,http://dx.doi.org/10.3201/eid1509.081573,PMC2819880,19788813,NO-CC CODE,"Feline coronavirus (FCoV) is endemic in feral cat populations and cat colonies, frequently preceding outbreaks of fatal feline infectious peritonitis (FIP). FCoV exhibits 2 biotypes: the pathogenic disease and a benign infection with feline enteric coronavirus (FECV). Uncertainty remains regarding whether genetically distinctive avirulent and virulent forms coexist or whether an avirulent form mutates in vivo, causing FIP. To resolve these alternative hypotheses, we isolated viral sequences from FCoV-infected clinically healthy and sick cats (8 FIP cases and 48 FECV-asymptomatic animals); 735 sequences from 4 gene segments were generated and subjected to phylogenetic analyses. Viral sequences from healthy cats were distinct from sick cats on the basis of genetic distances observed in the membrane and nonstructural protein 7b genes. These data demonstrate distinctive circulating virulent and avirulent strains in natural populations. In addition, 5 membrane protein amino acid residues with functional potential differentiated healthy cats from cats with FIP. These findings may have potential as diagnostic markers for virulent FIP-associated FCoV.",2009 Sep,"['Brown, Meredith A.', 'Troyer, Jennifer L.', 'Pecon-Slattery, Jill', 'Roelke, Melody E.', 'O’Brien, Stephen J.']",Emerg Infect Dis,,,False
5893fce58f11ff4e5510d0c4de7f9097c7a1869a,PMC,Genetics and Pathogenesis of Feline Infectious Peritonitis Virus,http://dx.doi.org/10.3201/eid1509.081573,PMC2819880,19788813,NO-CC CODE,"Feline coronavirus (FCoV) is endemic in feral cat populations and cat colonies, frequently preceding outbreaks of fatal feline infectious peritonitis (FIP). FCoV exhibits 2 biotypes: the pathogenic disease and a benign infection with feline enteric coronavirus (FECV). Uncertainty remains regarding whether genetically distinctive avirulent and virulent forms coexist or whether an avirulent form mutates in vivo, causing FIP. To resolve these alternative hypotheses, we isolated viral sequences from FCoV-infected clinically healthy and sick cats (8 FIP cases and 48 FECV-asymptomatic animals); 735 sequences from 4 gene segments were generated and subjected to phylogenetic analyses. Viral sequences from healthy cats were distinct from sick cats on the basis of genetic distances observed in the membrane and nonstructural protein 7b genes. These data demonstrate distinctive circulating virulent and avirulent strains in natural populations. In addition, 5 membrane protein amino acid residues with functional potential differentiated healthy cats from cats with FIP. These findings may have potential as diagnostic markers for virulent FIP-associated FCoV.",2009 Sep,"['Brown, Meredith A.', 'Troyer, Jennifer L.', 'Pecon-Slattery, Jill', 'Roelke, Melody E.', 'O’Brien, Stephen J.']",Emerg Infect Dis,,,True
261141d75b67dd38a19c1a4c9af037587c2357ff,PMC,"Increasing Incidence of Zygomycosis (Mucormycosis), France, 1997–2006",http://dx.doi.org/10.3201/eid1509.090334,PMC2819884,19788806,NO-CC CODE,"We analyzed hospital records to provide a population-based estimate of zygomycosis incidence and trends over a 10-year period at a national level in France. Data showed an increasing incidence from 0.7/million in 1997 to 1.2/million in 2006 (p<0.001). We compared our data with those from the French Mycosis Study Group, a recently established voluntary network of French mycologists coordinated by the National Reference Center for Mycoses and Antifungals. We documented that incidence of zygomycosis increased, particularly in patients with hematologic malignancies or bone marrow transplants. The role of previous exposure to antifungal drugs lacking activity against zygomycetes could explain this increase but does not appear exclusive. Incidence also increased in the population of patients with diabetes mellitus. We conclude that observed trends reflect a genuine increase of zygomycosis cases in at-risk populations.",2009 Sep,"['Bitar, Dounia', 'Van Cauteren, Dieter', 'Lanternier, Fanny', 'Dannaoui, Eric', 'Che, Didier', 'Dromer, Francoise', 'Desenclos, Jean-Claude', 'Lortholary, Olivier']",Emerg Infect Dis,,,True
d0c33264c3dc13c6c5f3a3d83bdde246bdc82165,PMC,"Clinical Assessment and Improved Diagnosis of Bocavirus-induced Wheezing in Children, Finland",http://dx.doi.org/10.3201/eid1509.090204,PMC2819894,19788810,NO-CC CODE,"Human bocavirus (HBoV) is a widespread respiratory virus. To improve diagnostic methods, we conducted immunoglobulin (Ig) G and IgM enzyme immunoassays with recombinant virus–like particles of HBoV as antigen. Acute-phase and follow-up serum samples from 258 wheezing children and single serum samples from 115 healthy adults in Finland were examined. Our assays had a sensitivity of 97% and a specificity of 99.5%. Of adults, 96% had immunity; none had an acute infection. Of 48 children with serologically diagnosed acute HBoV infections, 45 were viremic and 35 had virus in nasopharyngeal aspirates (NPAs). Of 39 HBoV NPA PCR–positive children co-infected with another virus, 64% had a serologically verified HBoV infection. HBoV caused illness of longer duration than rhinovirus and of equal severity to that of respiratory syncytial virus. Among children with bronchiolitis, >25% had acute HBoV infections. Accurate HBoV diagnosis requires serologic analysis or PCR of serum; PCR of NPAs alone is insufficient.",2009 Sep,"['Söderlund-Venermo, Maria', 'Lahtinen, Anne', 'Jartti, Tuomas', 'Hedman, Lea', 'Kemppainen, Kaisa', 'Lehtinen, Pasi', 'Allander, Tobias', 'Ruuskanen, Olli', 'Hedman, Klaus']",Emerg Infect Dis,,,True
4df45b8404d9de0b376a8ae3c282a517df36fe51,PMC,Two novel HLA-A*0201 T-cell epitopes in avian H5N1 viral nucleoprotein induced specific immune responses in HHD mice,http://dx.doi.org/10.1051/vetres/2009071,PMC2820229,19941812,NO-CC CODE,"The influenza A nucleoprotein (NP) is an attractive target for avian flu vaccine development because of its high conversancy in the evolutionary chain of the virus. Here we identified two novel HLA-A*0201 restricted NP epitopes, named H5N1 NP373-381 AMDSNTLEL (NP373) and NP458-466 FQGRGVFEL (NP458), using computational bioinformatic analysis. The NP peptides showed a high binding affinity to HLA-A*0201 on T2 cells, and were able to induce the activation of the cytotoxic T cells in the human peripheral blood mononuclear cells. We examined the potential of using NP373 and NP458 peptide sequences supplemented with a single-chain trimer as potential DNA vaccine candidates in an HHD transgenic mouse model. A gene gun delivery system was used for administrating the vaccine candidates into the animals. The results from cytotoxicity and ELISPOT assays indicated that a significant amount of IFN-γ was secreted by the T cells of the vaccinated mice, and the T cells were able to eliminate the corresponding peptide-loaded T2 cells. The discovery of these novel immunogenic NP peptides provides valuable information for avian flu vaccine design and construction.",2010 Nov 27 Mar-Apr,"['Cheung, Ying-Kit', 'Cheng, Samuel Chak-Sum', 'Ke, Yan', 'Xie, Yong']",Vet Res,,,True
58c0cc8bc91f5e92814df48b22321af4c7f75d53,PMC,Human Noroviruses in Swine and Cattle,http://dx.doi.org/10.3201/eid1308.070005,PMC2828081,17953089,NO-CC CODE,"Human noroviruses are the predominant cause of foodborne gastroenteritis worldwide. Strains of norovirus also exist that are uniquely associated with animals; their contribution to the incidence of human illness remains unclear. We tested animal fecal samples and identified GIII (bovine), GII.18 (swine), and GII.4 (human) norovirus sequences, demonstrating for the first time, to our knowledge, that GII.4-like strains can be present in livestock. In addition, we detected GII.4-like noroviral RNA from a retail meat sample. This finding highlights a possible route for indirect zoonotic transmission of noroviruses through the food chain.",2007 Aug,"['Mattison, Kirsten', 'Shukla, Anu', 'Cook, Angela', 'Pollari, Frank', 'Friendship, Robert', 'Kelton, David', 'Bidawid, Sabah', 'Farber, Jeffrey M.']",Emerg Infect Dis,,,True
b69fe5e231d41629e4620b18e90999022c72474d,PMC,"Molecular Epidemiology of Canine Parvovirus, Europe",http://dx.doi.org/10.3201/eid1308.070505,PMC2828098,17953097,NO-CC CODE,"Canine parvovirus (CPV), which causes hemorrhagic enteritis in dogs, has 3 antigenic variants: types 2a, 2b, and 2c. Molecular method assessment of the distribution of the CPV variants in Europe showed that the new variant CPV-2c is widespread in Europe and that the viruses are distributed in different countries.",2007 Aug,"['Decaro, Nicola', 'Desario, Costantina', 'Addie, Diane D.', 'Martella, Vito', 'Vieira, Maria João', 'Elia, Gabriella', 'Zicola, Angelique', 'Davis, Christopher', 'Thompson, Gertrude', 'Thiry, Ethienne', 'Truyen, Uwe', 'Buonavoglia, Canio']",Emerg Infect Dis,,,True
b6ed892b894ed62251a8cb78b5bca37318a03a4d,PMC,A VLP vaccine for epidemic Chikungunya virus protects non-human primates against infection,http://dx.doi.org/10.1038/nm.2105,PMC2834826,20111039,NO-CC CODE,"Chikungunya virus (CHIKV) has infected millions of people in Africa, Europe, and Asia1,2 since its re-emergence in Kenya in 2004. The severity of disease and spread of this epidemic virus present a serious public health threat in the absence of vaccines or anti-viral therapies. Here, we describe a novel vaccine that protects against emerging CHIKV infection of non-human primates (NHP). We show that selective expression of viral structural proteins gives rise to virus-like particles (VLPs) in vitro that resemble replication-competent alphaviruses. Immunization with these VLPs elicited neutralizing antibodies against envelope proteins from different CHIKV strains. Monkeys immunized with VLPs produced high titer neutralizing antibodies that protected against viremia after high dose challenge. We transferred these antibodies into immunodeficient mice, where they protected against subsequent lethal CHIKV challenge, establishing a humoral mechanism of protection. Immunization with alphavirus VLP vaccines represents a strategy to contain the spread of CHIKV and related pathogenic viruses in humans.",2010 Mar 28,"['Akahata, Wataru', 'Yang, Zhi-yong', 'Andersen, Hanne', 'Sun, Siyang', 'Holdaway, Heather A.', 'Kong, Wing-Pui', 'Lewis, Mark G.', 'Higgs, Stephen', 'Rossmann, Michael G.', 'Rao, Srinivas', 'Nabel, Gary J.']",Nat Med,,,True
f92ea65fa3771a913f8e3d7aff52c03fed0ae833,PMC,Plant polyphenols as dietary antioxidants in human health and disease,,PMC2835915,20716914,NO-CC CODE,"Polyphenols are secondary metabolites of plants and are generally involved in defense against ultraviolet radiation or aggression by pathogens. In the last decade, there has been much interest in the potential health benefits of dietary plant polyphenols as antioxidant. Epidemiological studies and associated meta-analyses strongly suggest that long term consumption of diets rich in plant polyphenols offer protection against development of cancers, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases. Here we present knowledge about the biological effects of plant polyphenols in the context of relevance to human health.",2009 Nov-Dec,"['Pandey, Kanti Bhooshan', 'Rizvi, Syed Ibrahim']",Oxid Med Cell Longev,,,True
81f9bd0e0377dbd8e67c579b6614003e6d825ab3,PMC,Early Days of Food and Environmental Virology,http://dx.doi.org/10.1007/s12560-010-9024-7,PMC2837245,20234839,NO-CC CODE,"In July 1962, the author joined the Food Research Institute (FRI), then at the University of Chicago, to become its food virologist. There was a limited record of waterborne viral disease outbreaks at the time; recorded data on foodborne outbreaks were fewer still. Laboratory environmental (water and wastewater) virology was in its infancy, and food virology was in gestation. Detection of viruses was most often attempted by inoculation of primary primate cell cultures, with observation for plaque formation or cytopathic effects. Focus was initially on enteroviruses and reoviruses. Environmental and food samples had to be liquefied if not already in liquid form; clarified to remove solids, bacteria, and fungi; and concentrated to a volume that could be tested in cell culture. Cytotoxicity was also a concern. Studies at the FRI and some other laboratories addressed all of these challenges. The FRI group was the World Health Organization’s Collaborating Center for Food Virology for many years. Other topics studied were virus inactivation as functions of temperature, time, matrix, disinfectants, and microbial action; peroral and ex-vivo infectivity; and the suitability of various virus surrogates for environmental monitoring and inactivation experiments. Detection of noroviruses and hepatitis A virus required molecular methods, most often RT-PCR. When it was found that inactivated virus often gave the same RT-PCR signal as that of infectious virus, sample treatments were sought, which would prevent false-positive test results. Many laboratories around the world have taken up food and environmental virology since 1962, with the result that a dedicated journal has been launched.",2010 Mar 4,"Cliver, Dean O.",Food Environ Virol,,,True
3c3572ba243d61e7631725669c8f88347fdbd5bc,PMC,"Prevalence of feline herpesvirus 1, feline calicivirus and Chlamydophila felis in clinically normal cats at a Korean animal shelter",http://dx.doi.org/10.4142/jvs.2008.9.2.207,PMC2839100,18487944,NO-CC CODE,"The prevalence of feline herpesvirus-1 (FHV-1), feline calicivirus (FCV), and Chlamydophila (C.) felis was studied in cats of an animal shelter in Korea. Total 78 cats without ocular and upper respiratory tract disease were examined. Specimens were obtained from ocular conjunctiva and oropharynx. Using multiplex polymerase chain reaction (PCR) and reverse transcription PCR, three pathogens were simultaneously detected. In examined 78 cats, 49 (63%) cats were positive for FHV-1. However, all specimens were negative for C. felis and FCV. In conclusion, many cats recovered from FHV-1 infection remain subclinical carriers in shelter environment.",2008 Jun 30,"['Kang, Byeong-Teck', 'Park, Hee-Myung']",J Vet Sci,,,True
dd6c1a719bd75ba7fb7c62291a676b39c99bb0bc,PMC,Molecular characterization and genogrouping of VP1 of aquatic birnavirus GC1 isolated from rockfish Sebastes schlegeli in Korea,http://dx.doi.org/10.4142/jvs.2008.9.1.85,PMC2839116,18296892,NO-CC CODE,"The cDNA nucleotide sequence of genome segment B encoding the VP1 protein was determined for the aquatic birnavirus GC1 isolated from the rockfish Sebastes schlegeli in Korea. The VP1 protein of GC1 contains a 2,538 bp open reading frame, which encodes a protein comprising 846 amino acid residues that has a predicted MW of 94 kDa. The sequence contains 6 potential Asn-X-Ser/Thr motifs. Eight potential Ser phosphorylation sites and 1 potential Tyr phophorylation site were also identified. GC1 contains the Leu-Lys-Asn (LKN) motif instead of the typical Gly-Asp-Asp (GDD) motif found in other aquatic birnaviruses. We also identified the GLPYIGKT motif, the putative GTP-binding site at amino acid position 248. In total, the VP1 regions of 22 birnavirus strains were compared for analyzing the genetic relationship among the family Birnaviridae. Based on the deduced amino acid sequences, GC1 was observed to be more closely related to the infectious pancreatic necrosis virus (IPNV) from the USA, Japan, and Korea than the IPNV from Europe. Further, aquatic birnaviruses containing GC1 and IPNV have genogroups that are distinct from those in the genus Avibirnaviruses and Entomo-birnaviruses. The birnavirusstrains were clustered into 5 genogroups based on their amino acid sequences. The marine aquatic birnaviruses (MABVs) containing GC1 were included in the MABV genogroup; the IPNV strains isolated from Korea, Japan, and the USA were included in genogroup 1 and the IPNV strains isolated primarily from Europe were included in genogroup 2. Avibirnaviruses and entomobirnaviruses were included in genogroup 3 and 4, respectively.",2008 Mar 31,"['Joh, Seong Joon', 'Shon, Chae Ik', 'Kang, Sung Won', 'Kim, Byoung Han', 'Jeong, Byung Yul', 'Lee, Kyung Gi', 'Kwon, Jun Hun', 'Heo, Gang Jun']",J Vet Sci,,,True
5560c5577076d3180d78439586d9ebe75653b20f,PMC,Modern approaches to understanding stress and disease susceptibility: A review with special emphasis on respiratory disease,,PMC2840576,20360883,NO-CC CODE,"Studies in animals and humans link both physical and psychological stress with an increased incidence and severity of respiratory infections. For this manuscript we define stress as the physiological responses an individual undergoes while adjusting to a continually changing environment. It is known that stressors of various types (psychological/physical) can alter the physiological levels of certain hormones, chemokines and cytokines. These alterations send information to the central nervous system to take necessary action which then sends messages to appropriate organs/tissues/cells to respond. These messages can either activate or suppress the immune system as needed and failure to compensate for this by the body can lead to serious health-related problems. Little is known how stress affects disease susceptibility, yet understanding this mechanism is important for developing effective treatments, and for improving health and food quality. The current review focuses on (a) the effects of psychological stressors in humans and animals, (b) various methodologies employed to understand stress responses and their outcomes, and (c) the current status of the attempts to correlate stress and disease with respiratory disease as model system. The methodologies included in this review span traditional epidemiological, behavioral and immunological studies to current high throughput genomic, proteomic, metabolomic/metabonomic approaches. With the advent of various newer omics and bioinformatics methodologies we postulate that it will become feasible to understand the mechanisms through which stress can influence disease onset. Although the literature in this area is limited because of the infancy of this research area, the objective of this review is to illustrate the power of new approaches to address complex biological questions. These new approaches will also aid in our understanding how these processes are related to the dynamics and kinetics of changes in expression of multiple genes at various levels.",2009 Jul 30,"['Aich, Palok', 'Potter, Andrew A', 'Griebel, Philip J']",Int J Gen Med,,,True
6993451f527d3f206e315e404687a38c97a495ff,PMC,Detection of multiple respiratory pathogens during primary respiratory infection: nasal swab versus nasopharyngeal aspirate using real-time polymerase chain reaction,http://dx.doi.org/10.1007/s10096-009-0865-7,PMC2840676,20111881,NO-CC CODE,"In this study, we present the multiple detection of respiratory viruses in infants during primary respiratory illness, investigate the sensitivity of nasal swabs and nasopharyngeal aspirates, and assess whether patient characteristics and viral load played a role in the sensitivity. Healthy infants were included at signs of first respiratory tract infection. Paired nasopharyngeal aspirates and nasal swabs were collected. Real-time polymerase chain reaction (PCR) was carried out for 11 respiratory pathogens. Paired nasopharyngeal aspirates and nasal swabs were collected in 98 infants. Rhinovirus (n = 67) and respiratory syncytial virus (n = 39) were the most frequently detected. Co-infection occurred in 48% (n = 45) of the infants. The sensitivity of the nasal swab was lower than the nasopharyngeal aspirate, in particular, for respiratory syncytial virus (51% vs. 100%) and rhinovirus (75% vs. 97%). The sensitivity of the nasal swab was strongly determined by the cycle threshold (CT) value (p < 0.001). The sensitivity of the swab for respiratory syncytial virus, but not rhinovirus, was 100% in children with severe symptoms (score ≥11). It is concluded that, for community-based studies and surveillance purposes, the nasal swab can be used, though the sensitivity is lower than the aspirate, in particular, for the detection of mild cases of respiratory syncytial virus (RSV) infection.",2010 Apr 29,"['Meerhoff, T. J.', 'Houben, M. L.', 'Coenjaerts, F. E. J.', 'Kimpen, J. L. L.', 'Hofland, R. W.', 'Schellevis, F.', 'Bont, L. J.']",Eur J Clin Microbiol Infect Dis,,,True
d050ed9690b0179835dca97985ab7ef2c843f230,PMC,Examining Landscape Factors Influencing Relative Distribution of Mosquito Genera and Frequency of Virus Infection,http://dx.doi.org/10.1007/s10393-009-0260-y,PMC2841756,19915916,NO-CC CODE,"Mosquito-borne infections cause some of the most debilitating human diseases, including yellow fever and malaria, yet we lack an understanding of how disease risk scales with human-driven habitat changes. We present an approach to study variation in mosquito distribution and concomitant viral infections on the landscape level. In a pilot study we analyzed mosquito distribution along a 10-km transect of a West African rainforest area, which included primary forest, secondary forest, plantations, and human settlements. Variation was observed in the abundance of Anopheles, Aedes,Culex, and Uranotaenia mosquitoes between the different habitat types. Screening of trapped mosquitoes from the different habitats led to the isolation of five uncharacterized viruses of the families Bunyaviridae, Coronaviridae, Flaviviridae, and Rhabdoviridae, as well as an unclassified virus. Polymerase chain reaction screening for these five viruses in individual mosquitoes indicated a trend toward infection with specific viruses in specific mosquito genera that differed by habitat. Based on these initial analyses, we believe that further work is indicated to investigate the impact of anthropogenic landscape changes on mosquito distribution and accompanying arbovirus infection.",2009 Jun 14,"['Junglen, S.', 'Kurth, A.', 'Kuehl, H.', 'Quan, P.-L.', 'Ellerbrok, H.', 'Pauli, G.', 'Nitsche, A.', 'Nunn, C.', 'Rich, S. M.', 'Lipkin, W. I.', 'Briese, T.', 'Leendertz, F. H.']",Ecohealth,,,True
8d7d39313cd9791fca858c229b4af66a8e0927ad,PMC,SAROTUP: Scanner and Reporter of Target-Unrelated Peptides,http://dx.doi.org/10.1155/2010/101932,PMC2842971,20339521,NO-CC CODE,"As epitope mimics, mimotopes have been widely utilized in the study of epitope prediction and the development of new diagnostics, therapeutics, and vaccines. Screening the random peptide libraries constructed with phage display or any other surface display technologies provides an efficient and convenient approach to acquire mimotopes. However, target-unrelated peptides creep into mimotopes from time to time through binding to contaminants or other components of the screening system. In this study, we present SAROTUP, a free web tool for scanning, reporting and excluding possible target-unrelated peptides from real mimotopes. Preliminary tests show that SAROTUP is efficient and capable of improving the accuracy of mimotope-based epitope mapping. It is also helpful for the development of mimotope-based diagnostics, therapeutics, and vaccines.",2010 Mar 21,"['Huang, Jian', 'Ru, Beibei', 'Li, Shiyong', 'Lin, Hao', 'Guo, Feng-Biao']",J Biomed Biotechnol,,,True
1e77d7c7edc8692bbe4056e0ea0bb52ffabafa96,PMC,DNA Vaccines: Developing New Strategies against Cancer,http://dx.doi.org/10.1155/2010/174378,PMC2846346,20368780,NO-CC CODE,"Due to their rapid and widespread development, DNA vaccines have entered into a variety of human clinical trials for vaccines against various diseases including cancer. Evidence that DNA vaccines are well tolerated and have an excellent safety profile proved to be of advantage as many clinical trials combines the first phase with the second, saving both time and money. It is clear from the results obtained in clinical trials that such DNA vaccines require much improvement in antigen expression and delivery methods to make them sufficiently effective in the clinic. Similarly, it is clear that additional strategies are required to activate effective immunity against poorly immunogenic tumor antigens. Engineering vaccine design for manipulating antigen presentation and processing pathways is one of the most important aspects that can be easily handled in the DNA vaccine technology. Several approaches have been investigated including DNA vaccine engineering, co-delivery of immunomodulatory molecules, safe routes of administration, prime-boost regimen and strategies to break the immunosuppressive networks mechanisms adopted by malignant cells to prevent immune cell function. Combined or single strategies to enhance the efficacy and immunogenicity of DNA vaccines are applied in completed and ongoing clinical trials, where the safety and tolerability of the DNA platform are substantiated. In this review on DNA vaccines, salient aspects on this topic going from basic research to the clinic are evaluated. Some representative DNA cancer vaccine studies are also discussed.",2010 Mar 28,"['Fioretti, Daniela', 'Iurescia, Sandra', 'Fazio, Vito Michele', 'Rinaldi, Monica']",J Biomed Biotechnol,,,True
bae793db127cecb4f94b4964d3ecad045b793848,PMC,TLR agonist–Stat3 siRNA conjugates: cell-specific gene silencing and enhanced antitumor immune responses,http://dx.doi.org/10.1038/nbt.1564,PMC2846721,19749770,NO-CC CODE,"Efficient delivery of siRNA to specific cell populations in vivo remains a formidable challenge to its successful therapeutic application. We describe a novel siRNA-based approach – synthetically linking siRNA to an oligonucleotide TLR9 agonist – that targets and silences genes in TLR9(+) myeloid cells and B cells, both of which are key components of the tumor microenvironment. Because Stat3 in tumor-associated immune cells suppresses antitumor immune responses and hinders TLR9-induced immune stimulation, we tested CpG-Stat3siRNA conjugates for anti-tumor effects. When injected locally at the tumor site or systemically through an intravenous route, the CpG-Stat3siRNA conjugates access tumor-associated dendritic cells, macrophages and B cells, inhibit Stat3 expression, leading to activation of tumor-associated immune cells, and ultimately potent anti-tumor immune responses. Our findings demonstrate the potential of TLR agonist-siRNA conjugates for targeted gene silencing coupled with TLR stimulation and immune activation in the tumor microenvironment.",2009 Oct 13,"['Kortylewski, Marcin', 'Swiderski, Piotr', 'Herrmann, Andreas', 'Wang, Lin', 'Kowolik, Claudia', 'Kujawski, Maciej', 'Lee, Heehyoung', 'Scuto, Anna', 'Liu, Yong', 'Yang, Chunmei', 'Deng, Jiehui', 'Soifer, Harris S.', 'Raubitschek, Andrew', 'Forman, Stephen', 'Rossi, John J.', 'Pardoll, Drew M.', 'Jove, Richard', 'Yu, Hua']",Nat Biotechnol,,,True
250511b53daafc621417d4c983bf82df2ca2bde8,PMC,TLR agonist–Stat3 siRNA conjugates: cell-specific gene silencing and enhanced antitumor immune responses,http://dx.doi.org/10.1038/nbt.1564,PMC2846721,19749770,NO-CC CODE,"Efficient delivery of siRNA to specific cell populations in vivo remains a formidable challenge to its successful therapeutic application. We describe a novel siRNA-based approach – synthetically linking siRNA to an oligonucleotide TLR9 agonist – that targets and silences genes in TLR9(+) myeloid cells and B cells, both of which are key components of the tumor microenvironment. Because Stat3 in tumor-associated immune cells suppresses antitumor immune responses and hinders TLR9-induced immune stimulation, we tested CpG-Stat3siRNA conjugates for anti-tumor effects. When injected locally at the tumor site or systemically through an intravenous route, the CpG-Stat3siRNA conjugates access tumor-associated dendritic cells, macrophages and B cells, inhibit Stat3 expression, leading to activation of tumor-associated immune cells, and ultimately potent anti-tumor immune responses. Our findings demonstrate the potential of TLR agonist-siRNA conjugates for targeted gene silencing coupled with TLR stimulation and immune activation in the tumor microenvironment.",2009 Oct 13,"['Kortylewski, Marcin', 'Swiderski, Piotr', 'Herrmann, Andreas', 'Wang, Lin', 'Kowolik, Claudia', 'Kujawski, Maciej', 'Lee, Heehyoung', 'Scuto, Anna', 'Liu, Yong', 'Yang, Chunmei', 'Deng, Jiehui', 'Soifer, Harris S.', 'Raubitschek, Andrew', 'Forman, Stephen', 'Rossi, John J.', 'Pardoll, Drew M.', 'Jove, Richard', 'Yu, Hua']",Nat Biotechnol,,,False
2b554bfe12a457f1092ae7b12537e48cb3392f67,PMC,Duration of Antibody Responses after Severe Acute Respiratory Syndrome,http://dx.doi.org/10.3201/eid1310.070576,PMC2851497,18258008,NO-CC CODE,"Among 176 patients who had had severe acute respiratory syndrome (SARS), SARS-specific antibodies were maintained for an average of 2 years, and significant reduction of immunoglobulin G–positive percentage and titers occurred in the third year. Thus, SARS patients might be susceptible to reinfection >3 years after initial exposure.",2007 Oct,"['Wu, Li-Ping', 'Wang, Nai-Chang', 'Chang, Yi-Hua', 'Tian, Xiang-Yi', 'Na, Dan-Yu', 'Zhang, Li-Yuan', 'Zheng, Lei', 'Lan, Tao', 'Wang, Lin-Fa', 'Liang, Guo-Dong']",Emerg Infect Dis,,,True
64f75ab0933b2639497b4d607de656a09a1a3284,PMC,Evolutionary Relationships between Bat Coronaviruses and Their Hosts,http://dx.doi.org/10.3201/eid1310.070448,PMC2851503,18258002,NO-CC CODE,"Recent studies have suggested that bats are the natural reservoir of a range of coronaviruses (CoVs), and that rhinolophid bats harbor viruses closely related to the severe acute respiratory syndrome (SARS) CoV, which caused an outbreak of respiratory illness in humans during 2002–2003. We examined the evolutionary relationships between bat CoVs and their hosts by using sequence data of the virus RNA-dependent RNA polymerase gene and the bat cytochrome b gene. Phylogenetic analyses showed multiple incongruent associations between the phylogenies of rhinolophid bats and their CoVs, which suggested that host shifts have occurred in the recent evolutionary history of this group. These shifts may be due to either virus biologic traits or host behavioral traits. This finding has implications for the emergence of SARS and for the potential future emergence of SARS-CoVs or related viruses.",2007 Oct,"['Cui, Jie', 'Han, Naijian', 'Streicker, Daniel', 'Li, Gang', 'Tang, Xianchun', 'Shi, Zhengli', 'Hu, Zhihong', 'Zhao, Guoping', 'Fontanet, Arnaud', 'Guan, Yi', 'Wang, Linfa', 'Jones, Gareth', 'Field, Hume E.', 'Daszak, Peter', 'Zhang, Shuyi']",Emerg Infect Dis,,,True
d02034376ac45efa3806785215aa2d9619c7abfa,PMC,Personal Protective Equipment and Antiviral Drug Use during Hospitalization for Suspected Avian or Pandemic Influenza(1),http://dx.doi.org/10.3201/eid1310.070033,PMC2851524,18258004,NO-CC CODE,"For pandemic influenza planning, realistic estimates of personal protective equipment (PPE) and antiviral medication required for hospital healthcare workers (HCWs) are vital. In this simulation study, a patient with suspected avian or pandemic influenza (API) sought treatment at 9 Australian hospital emergency departments where patient–staff interactions during the first 6 hours of hospitalization were observed. Based on World Health Organization definitions and guidelines, the mean number of “close contacts” of the API patient was 12.3 (range 6–17; 85% HCWs); mean “exposures” were 19.3 (range 15–26). Overall, 20–25 PPE sets were required per patient, with variable HCW compliance for wearing these items (93% N95 masks, 77% gowns, 83% gloves, and 73% eye protection). Up to 41% of HCW close contacts would have qualified for postexposure antiviral prophylaxis. These data indicate that many current national stockpiles of PPE and antiviral medication are likely inadequate for a pandemic.",2007 Oct,"['Swaminathan, Ashwin', 'Martin, Rhea', 'Gamon, Sandi', 'Aboltins, Craig', 'Athan, Eugene', 'Braitberg, George', 'Catton, Michael G.', 'Cooley, Louise', 'Dwyer, Dominic E.', 'Edmonds, Deidre', 'Eisen, Damon P.', 'Hosking, Kelly', 'Hughes, Andrew J.', 'Johnson, Paul D.', 'Maclean, Andrew V', 'O’Reilly, Mary', 'Peters, S. Erica', 'Stuart, Rhonda L.', 'Moran, Rodney', 'Grayson, M. Lindsay']",Emerg Infect Dis,,,True
ec6675c47e1dc4e4227c9ed3345103a82baaf09b,PMC,Rapid Field Immunoassay for Detecting Antibody to Sin Nombre Virus in Deer Mice,http://dx.doi.org/10.3201/eid1310.070383,PMC2851528,18258020,NO-CC CODE,We developed a 1-hour field enzyme immunoassay (EIA) for detecting antibody to Sin Nombre virus in deer mice (Peromyscus maniculatus). The assay specificity and sensitivity were comparable to those of a standard EIA. This test will permit identification of rodents with antibody to this and perhaps other hantaviruses.,2007 Oct,"['Schountz, Tony', 'Calisher, Charles H.', 'Richens, Tiffany R.', 'Rich, Audrey A.', 'Doty, Jeffrey B.', 'Hughes, Mark T.', 'Beaty, Barry J.']",Emerg Infect Dis,,,True
f3ead6ffa56b8d94abfe97c81efa762233a7aa13,PMC,Global Public Health Security,http://dx.doi.org/10.3201/eid1013.070732,PMC2851539,18257985,NO-CC CODE,National public health institutes will play a key role in implementation of the revised International Health Regulations.,2007 Oct,"['Rodier, Guénaël', 'Greenspan, Allison L.', 'Hughes, James M.', 'Heymann, David L.']",Emerg Infect Dis,,,True
6266766fd9da3175d27c27b38db9054b7dd45c17,PMC,"Risk of Importing Zoonotic Diseases through Wildlife Trade, United States",http://dx.doi.org/10.3201/eid1511.090467,PMC2857234,19891857,NO-CC CODE,"The United States is the world’s largest wildlife importer, and imported wild animals represent a potential source of zoonotic pathogens. Using data on mammals imported during 2000–2005, we assessed their potential to host 27 selected risk zoonoses and created a risk assessment that could inform policy making for wildlife importation and zoonotic disease surveillance. A total of 246,772 mammals in 190 genera (68 families) were imported. The most widespread agents of risk zoonoses were rabies virus (in 78 genera of mammals), Bacillus anthracis (57), Mycobacterium tuberculosis complex (48), Echinococcus spp. (41), and Leptospira spp. (35). Genera capable of harboring the greatest number of risk zoonoses were Canis and Felis (14 each), Rattus (13), Equus (11), and Macaca and Lepus (10 each). These findings demonstrate the myriad opportunities for zoonotic pathogens to be imported and suggest that, to ensure public safety, immediate proactive changes are needed at multiple levels.",2009 Nov,"['Pavlin, Boris I.', 'Schloegel, Lisa M.', 'Daszak, Peter']",Emerg Infect Dis,,,True
863f0c3fde068d1ef7b13ac852e98dea477559b0,PMC,"Risk of Importing Zoonotic Diseases through Wildlife Trade, United States",http://dx.doi.org/10.3201/eid1511.090467,PMC2857234,19891857,NO-CC CODE,"The United States is the world’s largest wildlife importer, and imported wild animals represent a potential source of zoonotic pathogens. Using data on mammals imported during 2000–2005, we assessed their potential to host 27 selected risk zoonoses and created a risk assessment that could inform policy making for wildlife importation and zoonotic disease surveillance. A total of 246,772 mammals in 190 genera (68 families) were imported. The most widespread agents of risk zoonoses were rabies virus (in 78 genera of mammals), Bacillus anthracis (57), Mycobacterium tuberculosis complex (48), Echinococcus spp. (41), and Leptospira spp. (35). Genera capable of harboring the greatest number of risk zoonoses were Canis and Felis (14 each), Rattus (13), Equus (11), and Macaca and Lepus (10 each). These findings demonstrate the myriad opportunities for zoonotic pathogens to be imported and suggest that, to ensure public safety, immediate proactive changes are needed at multiple levels.",2009 Nov,"['Pavlin, Boris I.', 'Schloegel, Lisa M.', 'Daszak, Peter']",Emerg Infect Dis,,,True
f8f67ffc1bc2ed32272f79ff80c26beda4bcda86,PMC,"Contagion and Chaos: Disease, Ecology, and National Security in the Era of Globalization",http://dx.doi.org/10.3201/eid1511.090577,PMC2857238,,NO-CC CODE,,2009 Nov,"Morse, Stephen A.",Emerg Infect Dis,,,False
8b2141d00757fe30e235fc16fecc7106c96b3088,PMC,"Health Status of Visitors and Temporary Residents, United States",http://dx.doi.org/10.3201/eid1511.090938,PMC2857256,19891856,NO-CC CODE,"Human mobility has always been associated with the spread of infection, and mobility of nonimmigrant visitors and temporary residents to the United States is increasing, from ≈12 million in 1987 to ≈37 million in 2007. Lack of information about the health status of these populations upon arrival and their need for and use of medical services in the United States hinders development of public health policy, education, and provision of adequate clinical care. After these issues and needs are clarified, intervention programs should be developed to increase access and decrease the disparities of care experienced by these populations.",2009 Nov,"['Yanni, Emad A.', 'Marano, Nina', 'Stauffer, William M.', 'Barnett, Elizabeth D.', 'Cano, Maria', 'Cetron, Martin S.']",Emerg Infect Dis,,,True
d930538d1883ce56182169efa9d90113a1fb00f6,PMC,"Health Status of Visitors and Temporary Residents, United States",http://dx.doi.org/10.3201/eid1511.090938,PMC2857256,19891856,NO-CC CODE,"Human mobility has always been associated with the spread of infection, and mobility of nonimmigrant visitors and temporary residents to the United States is increasing, from ≈12 million in 1987 to ≈37 million in 2007. Lack of information about the health status of these populations upon arrival and their need for and use of medical services in the United States hinders development of public health policy, education, and provision of adequate clinical care. After these issues and needs are clarified, intervention programs should be developed to increase access and decrease the disparities of care experienced by these populations.",2009 Nov,"['Yanni, Emad A.', 'Marano, Nina', 'Stauffer, William M.', 'Barnett, Elizabeth D.', 'Cano, Maria', 'Cetron, Martin S.']",Emerg Infect Dis,,,False
42660ed19540a2bb59a9fb7481cb0c526fd12846,PMC,Multicenter EuroTravNet/GeoSentinel Study of Travel-related Infectious Diseases in Europe,http://dx.doi.org/10.3201/eid1511.091147,PMC2857260,19891866,NO-CC CODE,"We analyzed prospective data on 17,228 European patients who sought treatment at GeoSentinel sites from 1997 to 2007. Gastrointestinal illness (particularly in tourists), fever (those visiting friends and relatives [VFRs]), and skin disorders (in tourists) were the most common reasons for seeking medical care. Diagnoses varied by country of origin, region visited, or categories of travelers. VFRs who returned from sub-Saharan Africa and Indian Ocean islands were more likely to experience falciparum malaria than any other group. Multiple correspondence analysis identified Italian, French, and Swiss VFRs and expatriate travelers to sub-Saharan Africa and Indian Ocean Islands as most likely to exhibit febrile illnesses. German tourists to Southeast and south-central Asia were most likely to seek treatment for acute diarrhea. Non-European travelers (12,663 patients from other industrialized countries) were less likely to acquire certain travel-associated infectious diseases. These results should be considered in the practice of travel medicine and development of health recommendations for European travelers.",2009 Nov,"['Gautret, Philippe', 'Schlagenhauf, Patricia', 'Gaudart, Jean', 'Castelli, Francesco', 'Brouqui, Philippe', 'von Sonnenburg, Frank', 'Loutan, Louis', 'Parola, Philippe', None]",Emerg Infect Dis,,,True
94eae6202d688c4ab3c879c3706117feb385e3d1,PMC,Multicenter EuroTravNet/GeoSentinel Study of Travel-related Infectious Diseases in Europe,http://dx.doi.org/10.3201/eid1511.091147,PMC2857260,19891866,NO-CC CODE,"We analyzed prospective data on 17,228 European patients who sought treatment at GeoSentinel sites from 1997 to 2007. Gastrointestinal illness (particularly in tourists), fever (those visiting friends and relatives [VFRs]), and skin disorders (in tourists) were the most common reasons for seeking medical care. Diagnoses varied by country of origin, region visited, or categories of travelers. VFRs who returned from sub-Saharan Africa and Indian Ocean islands were more likely to experience falciparum malaria than any other group. Multiple correspondence analysis identified Italian, French, and Swiss VFRs and expatriate travelers to sub-Saharan Africa and Indian Ocean Islands as most likely to exhibit febrile illnesses. German tourists to Southeast and south-central Asia were most likely to seek treatment for acute diarrhea. Non-European travelers (12,663 patients from other industrialized countries) were less likely to acquire certain travel-associated infectious diseases. These results should be considered in the practice of travel medicine and development of health recommendations for European travelers.",2009 Nov,"['Gautret, Philippe', 'Schlagenhauf, Patricia', 'Gaudart, Jean', 'Castelli, Francesco', 'Brouqui, Philippe', 'von Sonnenburg, Frank', 'Loutan, Louis', 'Parola, Philippe', None]",Emerg Infect Dis,,,False
940a99850a2fe93223a5ff0d9bb95869094a4a8f,PMC,Globally Mobile Populations and the Spread of Emerging Pathogens,http://dx.doi.org/10.3201/eid1511.091426,PMC2857263,19891855,NO-CC CODE,,2009 Nov,"['Arguin, Paul M.', 'Marano, Nina', 'Freedman, David O.']",Emerg Infect Dis,,,True
7415b0e3fd0142110b218a154658e0171feb4a91,PMC,Fecal Viral Concentration and Diarrhea in Norovirus Gastroenteritis,http://dx.doi.org/10.3201/eid1309.061535,PMC2857278,18252121,NO-CC CODE,Fecal viral concentrations of 40 patients infected with norovirus genogroup GII.4 correlated with diarrhea duration and frequency of vomiting. Higher viral concentration and older age were independently associated with prolonged diarrhea (>4 days). These findings provide information on the pathogenesis and transmission of norovirus infections.,2007 Sep,"['Lee, Nelson', 'Chan, Martin C.W.', 'Wong, Bonnie', 'Choi, K.W.', 'Sin, Winnie', 'Lui, Grace', 'Chan, Paul K.S.', 'Lai, Raymond W.M.', 'Cockram, C.S.', 'Sung, Joseph J.Y.', 'Leung, Wai K.']",Emerg Infect Dis,,,True
7a776da1c0d3e0368750bd6ef1984d371b97b102,PMC,Frequent Travelers and Rate of Spread of Epidemics,http://dx.doi.org/10.3201/eid1309.070081,PMC2857283,18252097,NO-CC CODE,"A small proportion of air travelers make disproportionately more journeys than the rest of travelers. They also tend to interact predominantly with other frequent travelers in hotels and airport lounges. This group has the potential to accelerate global spread of infectious respiratory diseases. Using an epidemiologic model, we simulated exportation of cases from severe acute respiratory syndrome–like and influenza-like epidemics in a population for which a small proportion travel more frequently than the rest. Our simulations show that frequent travelers accelerate international spread of epidemics only if they are infected early in an outbreak and the outbreak does not expand rapidly. If the epidemic growth rate is high, as is likely for pandemic influenza, heterogeneities in travel are frequently overwhelmed by the large number of infected persons in the majority population and the resulting high probability that some of these persons will take an international flight.",2007 Sep,"['Hollingsworth, T. Déirdre', 'Ferguson, Neil M.', 'Anderson, Roy M.']",Emerg Infect Dis,,,True
4a7b22608c2a923a9b0bba5938c19a3a5d3cb3e2,PMC,Frequent Travelers and Rate of Spread of Epidemics,http://dx.doi.org/10.3201/eid1309.070081,PMC2857283,18252097,NO-CC CODE,"A small proportion of air travelers make disproportionately more journeys than the rest of travelers. They also tend to interact predominantly with other frequent travelers in hotels and airport lounges. This group has the potential to accelerate global spread of infectious respiratory diseases. Using an epidemiologic model, we simulated exportation of cases from severe acute respiratory syndrome–like and influenza-like epidemics in a population for which a small proportion travel more frequently than the rest. Our simulations show that frequent travelers accelerate international spread of epidemics only if they are infected early in an outbreak and the outbreak does not expand rapidly. If the epidemic growth rate is high, as is likely for pandemic influenza, heterogeneities in travel are frequently overwhelmed by the large number of infected persons in the majority population and the resulting high probability that some of these persons will take an international flight.",2007 Sep,"['Hollingsworth, T. Déirdre', 'Ferguson, Neil M.', 'Anderson, Roy M.']",Emerg Infect Dis,,,False
66d2443a9cacf7efd16112043485ce2692af1c2b,PMC,Disseminated Bocavirus Infection after Stem Cell Transplant,http://dx.doi.org/10.3201/eid1309.070318,PMC2857292,18252130,NO-CC CODE,,2007 Sep,"['Schenk, Thomas', 'Strahm, Brigitte', 'Kontny, Udo', 'Hufnagel, Markus', 'Neumann-Haefelin, Dieter', 'Falcone, Valeria']",Emerg Infect Dis,,,True
5bb307428f45e725c931894d2ed7d06d7f8d0991,PMC,Coronavirus Antibodies in African Bat Species,http://dx.doi.org/10.3201/eid1309.070342,PMC2857293,18252111,NO-CC CODE,"Asian bats have been identified as potential reservoir hosts of coronaviruses associated with severe acute respiratory syndrome (SARS-CoV). We detected antibody reactive with SARS-CoV antigen in 47 (6.7%) of 705 bat serum specimens comprising 26 species collected in Africa; thus, African bats may harbor agents related to putative group 4 CoV.",2007 Sep,"['Müller, Marcel A.', 'Paweska, Janusz T.', 'Leman, Patricia A.', 'Drosten, Christian', 'Grywna, Klaus', 'Kemp, Alan', 'Braack, Leo', 'Sonnenberg, Karen', 'Niedrig, Matthias', 'Swanepoel, Robert']",Emerg Infect Dis,,,True
397db76eef397c31bbc72af60ccd55ca7e9c4d76,PMC,Coronavirus Antibodies in African Bat Species,http://dx.doi.org/10.3201/eid1309.070342,PMC2857293,18252111,NO-CC CODE,"Asian bats have been identified as potential reservoir hosts of coronaviruses associated with severe acute respiratory syndrome (SARS-CoV). We detected antibody reactive with SARS-CoV antigen in 47 (6.7%) of 705 bat serum specimens comprising 26 species collected in Africa; thus, African bats may harbor agents related to putative group 4 CoV.",2007 Sep,"['Müller, Marcel A.', 'Paweska, Janusz T.', 'Leman, Patricia A.', 'Drosten, Christian', 'Grywna, Klaus', 'Kemp, Alan', 'Braack, Leo', 'Sonnenberg, Karen', 'Niedrig, Matthias', 'Swanepoel, Robert']",Emerg Infect Dis,,,False
125d62b8501fb7db5ffe3d173e9f805c568df5b4,PMC,Precautionary Behavior in Response to Perceived Threat of Pandemic Influenza,http://dx.doi.org/10.3201/eid1309.070372,PMC2857294,18252100,NO-CC CODE,"Faced with an epidemic of an infectious disease, persons may take precautionary actions to try to reduce their risk. Such actions include avoiding situations that persons perceive to be risky, which can have negative health and economic effects. Therefore, we conducted a population-based survey of persons’ precautionary actions in response to a hypothetical influenza pandemic. For the 5 European and 3 Asian regions that had been affected by severe acute respiratory syndrome, the pattern of reported precautionary action was broadly similar across the regions; ≈75% of respondents reported that they would avoid public transportation and 20%–30% would try to stay indoors. Some regional differences were noted; Europeans were more likely than Asians to avoid places of entertainment, and Asians were more likely to avoid seeing physicians. This international survey provides insight into what might be expected during an influenza pandemic.",2007 Sep,"['Sadique, M. Zia', 'Edmunds, W. John', 'Smith, Richard D.', 'Meerding, William Jan', 'de Zwart, Onno', 'Brug, Johannes', 'Beutels, Philippe']",Emerg Infect Dis,,,True
4cb9c6ef889605b3149ab8b59c8258074067ba04,PMC,Detection of Group 1 Coronaviruses in Bats in North America,http://dx.doi.org/10.3201/eid1309.070491,PMC2857301,18252098,NO-CC CODE,"The epidemic of severe acute respiratory syndrome (SARS) was caused by a newly emerged coronavirus (SARS-CoV). Bats of several species in southern People’s Republic of China harbor SARS-like CoVs and may be reservoir hosts for them. To determine whether bats in North America also harbor coronaviruses, we used reverse transcription–PCR to detect coronavirus RNA in bats. We found coronavirus RNA in 6 of 28 fecal specimens from bats of 2 of 7 species tested. The prevalence of viral RNA shedding was high: 17% in Eptesicus fuscus and 50% in Myotis occultus. Sequence analysis of a 440-bp amplicon in gene 1b showed that these Rocky Mountain bat coronaviruses formed 3 clusters in phylogenetic group 1 that were distinct from group 1 coronaviruses of Asian bats. Because of the potential for bat coronaviruses to cause disease in humans and animals, further surveillance and characterization of bat coronaviruses in North America are needed.",2007 Sep,"['Dominguez, Samuel R.', 'O’Shea, Thomas J.', 'Oko, Lauren M.', 'Holmes, Kathryn V.']",Emerg Infect Dis,,,True
d7f5e5abde02015d22f7738d6db889db53fe5863,PMC,“Nature Hath Fram’d Strange Fellows in Her Time”,http://dx.doi.org/10.3201/eid1309.000000,PMC2857308,,NO-CC CODE,,2007 Sep,"Potter, Polyxeni",Emerg Infect Dis,,,True
aeae3e593ea4d3d0b59c83839837be75d2ea47d5,PMC,Induction of type I interferon by RNA viruses: cellular receptors and their substrates,http://dx.doi.org/10.1007/s00726-009-0374-0,PMC2860555,19882216,NO-CC CODE,"Virus recognition and induction of interferon (IFN) are critical components of the innate immune system. The Toll-like receptor (TLR) and RIG-I-like receptor families have been characterized as key players in RNA virus detection. Signaling cascades initiated by these receptors are crucial for establishment of an IFN signaling mediated antiviral state in infected and neighboring cells and containment of virus replication as well as initiation of the adaptive immune response. In this review, we focus on the diverse and overlapping functions of these receptors, their physiological importance, and respective viral inducers. We highlight the roles of TRL3, TLR7/8, retinoic acid inducible gene I, melanoma differentiation-associated gene 5, and the RNA molecules responsible for activating these viral sensors.",2010 May 1,"['Baum, Alina', 'García-Sastre, Adolfo']",Amino Acids,,,True
5f7a4ea047afec2cad9f019c118233f41057084f,PMC,Generation of stable monoclonal antibody-producing BCR(+) human memory B cells by genetic programming,http://dx.doi.org/10.1038/nm.2071,PMC2861345,20023635,NO-CC CODE,"B cell lymphoma (BCL)6 and Bcl-xL are expressed in germinal center (GC) B cells and enable them to endure the proliferative and mutagenic environment of the GC. By introducing these genes into peripheral blood memory B cells and culturing these cells with factors produced by follicular helper T cells, CD40L and IL-21, we convert them to highly proliferating, cell surface BCR positive, Ig-secreting B cells with features of GC B cells including expression of activation-induced cytidine deaminase. We generated cloned lines of B cells specific for respiratory syncytial virus and used these cells as a source of antibodies that effectively neutralized this virus in vivo. This method provides a new tool to study GC B cell biology, signal transduction through antigen-specific B cell receptors, and for the rapid generation of high affinity human monoclonal antibodies.",2010 Jan 20,"['Kwakkenbos, Mark J.', 'Diehl, Sean A.', 'Yasuda, Etsuko', 'Bakker, Arjen Q.', 'van Geelen, Caroline M.M.', 'Lukens, Michaël V.', 'van Bleek, Grada M.', 'Widjojoatmodjo, Myra N.', 'Bogers, Willy M.J.M.', 'Mei, Henrik', 'Radbruch, Andreas', 'Scheeren, Ferenc A.', 'Spits, Hergen', 'Beaumont, Tim']",Nat Med,,,True
f5f5f2c5e7570a4152e6bbdecada50edc34a786d,PMC,Generation of stable monoclonal antibody-producing BCR(+) human memory B cells by genetic programming,http://dx.doi.org/10.1038/nm.2071,PMC2861345,20023635,NO-CC CODE,"B cell lymphoma (BCL)6 and Bcl-xL are expressed in germinal center (GC) B cells and enable them to endure the proliferative and mutagenic environment of the GC. By introducing these genes into peripheral blood memory B cells and culturing these cells with factors produced by follicular helper T cells, CD40L and IL-21, we convert them to highly proliferating, cell surface BCR positive, Ig-secreting B cells with features of GC B cells including expression of activation-induced cytidine deaminase. We generated cloned lines of B cells specific for respiratory syncytial virus and used these cells as a source of antibodies that effectively neutralized this virus in vivo. This method provides a new tool to study GC B cell biology, signal transduction through antigen-specific B cell receptors, and for the rapid generation of high affinity human monoclonal antibodies.",2010 Jan 20,"['Kwakkenbos, Mark J.', 'Diehl, Sean A.', 'Yasuda, Etsuko', 'Bakker, Arjen Q.', 'van Geelen, Caroline M.M.', 'Lukens, Michaël V.', 'van Bleek, Grada M.', 'Widjojoatmodjo, Myra N.', 'Bogers, Willy M.J.M.', 'Mei, Henrik', 'Radbruch, Andreas', 'Scheeren, Ferenc A.', 'Spits, Hergen', 'Beaumont, Tim']",Nat Med,,,True
9d77f5c67963a68f5ede5bf53e95fdb03270fd2b,PMC,Triggering DTH and CTL Activity by fd Filamentous Bacteriophages: Role of CD4+ T Cells in Memory Responses,http://dx.doi.org/10.1155/2010/894971,PMC2862324,20454650,NO-CC CODE,"The ability of fd bacteriophage particles to trigger different arms of the immune system has been previously shown by us with particular emphasis on the ability of phages to raise CTL responses in vitro and in vivo. Here we show that fd virions in the absence of adjuvants are able to evoke a DTH reaction mediated by antigen specific CD8+ T cells. In addition, we analyzed the induction of CTL responses in mice depleted of CD4+ T cells, and we observed that short-term secondary CTL responses were induced in the absence of CD4+ T cells while induction of long-term memory CTLs required the presence of CD4+ T lymphocytes. These results examine the cellular mechanism at the basis of fd efficiency and provide new elements to further validate the use of fd particles for eliciting and monitoring antigen-specific CTLs.",2010 Apr 29,"['Del Pozzo, Giovanna', 'Mascolo, Dina', 'Sartorius, Rossella', 'Citro, Alessandra', 'Barba, Pasquale', ""D'Apice, Luciana"", 'De Berardinis, Piergiuseppe']",J Biomed Biotechnol,,,True
3aa5c9f53c616efdef4103a7e8c3ebf433437a83,PMC,"Human Bocavirus 2 in Children, South Korea",http://dx.doi.org/10.3201/eid1510.090337,PMC2866402,19861084,NO-CC CODE,,2009 Oct,"['Han, Tae-Hee', 'Chung, Ju-Young', 'Hwang, Eung-Soo']",Emerg Infect Dis,,,True
ecee696015fbe0e5ec5d1a7c560fc8d1191d95a1,PMC,Sequence analysis of the S1 glycoprotein gene of infectious bronchitis viruses: identification of a novel phylogenetic group in Korea,http://dx.doi.org/10.4142/jvs.2007.8.4.401,PMC2868157,17993755,NO-CC CODE,"Twelve Korean infectious bronchitis viruses (IBVs) were isolated in the field from chickens suspected of being carriers of infectious bronchitis between 2001 and 2003. The S1 glycoprotein genes of these IBV isolates were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) and analyzed by restriction fragment length polymorphism (RFLP) analysis. These Korean IBV isolates were classified into three groups according to their RFLP patterns obtained using the restriction enzyme HaeIII. Half of the twelve isolates were similar to the KM91 RFLP pattern, which is a common pattern in Korea. Three more isolates were related to the Arkansas strain pattern, but with some unique variations. The other three viruses showed variant RFLP patterns. For a comparison with the published sequences for non-Korean IBV strains, amplified PCR products from the twelve isolates were cloned and sequenced. The Korean IBV field isolates had 71.2-99.7% nucleotide sequence homology with each other and 45.9-80.7% nucleotide sequence homology with non-Korean IBV strains. With respect to the deduced amino acid sequence, the Korean IBV isolates had 71.5-99.3% similarity with each other and 44.9-80.3% similarity with non-Korean IBV strains. Phylogenetic tree analysis revealed that some of the IBV isolates appear to belong to a new group, different from the non-Korean IBV strains or from previously isolated Korean IBV strains. Specifically, the new Korean IBV isolates K10217-03, K3-3 and K1255-03 represented a separate group. These findings suggest that the Korean IBVs appear to be continuously evolving.",2007 Dec 31,"['Jang, Ji-Hyun', 'Sung, Haan-Woo', 'Song, Chang-Seon', 'Kwon, Hyuk-Moo']",J Vet Sci,,,True
3ac3823b31229b9754a336bf17f5ff76fdcaadf2,PMC,Production of specific antibodies against SARS-coronavirus nucleocapsid protein without cross reactivity with human coronaviruses 229E and OC43,http://dx.doi.org/10.4142/jvs.2010.11.2.165,PMC2873818,20458159,NO-CC CODE,"Severe acute respiratory syndrome (SARS) is a life-threatening disease for which accurate diagnosis is essential. Although many tools have been developed for the diagnosis of SARS, false-positive reactions in negative sera may occur because of cross-reactivity with other coronaviruses. We have raised polyclonal and monoclonal antibodies (Abs) using a recombinant form of the SARS virus nucleocapsid protein. Cross-reactivity of these anti-SARS Abs against human coronavirus (HCoV) 229E and HCoV OC43 were determined by Western blotting. The Abs produced reacted with recombinant SARS virus nucleocapsid protein, but not with HCoV 229E or HCoV OC43.",2010 Jun 11,"['Lee, Hyun-Kyoung', 'Lee, Byoung-Hee', 'Seok, Seung-Hyeok', 'Baek, Min-Won', 'Lee, Hui-Young', 'Kim, Dong-Jae', 'Na, Yi-Rang', 'Noh, Kyoung-Jin', 'Park, Sung-Hoon', 'Kumar, Dutta Noton', 'Kariwa, Hiroaki', 'Nakauchi, Mina', 'Heo, Suk-Jin', 'Park, Jae-Hak']",J Vet Sci,,,True
844952cd4f3326959a4bf2e50bc64ab436b8ded8,PMC,"Public Health Threat of New, Reemerging, and Neglected Zoonoses in the Industrialized World",http://dx.doi.org/10.3201/eid1601.081467,PMC2874344,20031035,NO-CC CODE,"Microbiologic infections acquired from animals, known as zoonoses, pose a risk to public health. An estimated 60% of emerging human pathogens are zoonotic. Of these pathogens, >71% have wildlife origins. These pathogens can switch hosts by acquiring new genetic combinations that have altered pathogenic potential or by changes in behavior or socioeconomic, environmental, or ecologic characteristics of the hosts. We discuss causal factors that influence the dynamics associated with emergence or reemergence of zoonoses, particularly in the industrialized world, and highlight selected examples to provide a comprehensive view of their range and diversity.",2010 Jan,"['Cutler, Sally J.', 'Fooks, Anthony R.', 'van der Poel, Wim H. M.']",Emerg Infect Dis,,,True
105aab8d21e803d2b363183c263a90ce47a9c5ae,PMC,Acute Encephalopathy Associated with Influenza A Infection in Adults,http://dx.doi.org/10.3201/eid1601.090077,PMC2874350,20031062,NO-CC CODE,"We report acute encephalopathy associated with influenza A infection in 3 adults. We detected high cerebrospinal fluid (CSF) and plasma concentrations of CXCL8/IL-8 and CCL2/MCP-1 (CSF/plasma ratios >3), and interleukin-6, CXCL10/IP-10, but no evidence of viral neuroinvasion. Patients recovered without sequelae. Hyperactivated cytokine response may play a role in pathogenesis.",2010 Jan,"['Lee, Nelson', 'Wong, Chun Kwok', 'Chan, Paul K.S.', 'Lindegardh, Niklas', 'White, Nicholas J.', 'Hayden, Frederick G.', 'Wong, Edward H.C.', 'Wong, Ka Shing', 'Cockram, Clive S.', 'Sung, Joseph J.Y.', 'Hui, David S.C.']",Emerg Infect Dis,,,True
a1f353aafa8d3dfc2e76c6d3d75df0342c8a9e6e,PMC,Acute Encephalopathy Associated with Influenza A Infection in Adults,http://dx.doi.org/10.3201/eid1601.090077,PMC2874350,20031062,NO-CC CODE,"We report acute encephalopathy associated with influenza A infection in 3 adults. We detected high cerebrospinal fluid (CSF) and plasma concentrations of CXCL8/IL-8 and CCL2/MCP-1 (CSF/plasma ratios >3), and interleukin-6, CXCL10/IP-10, but no evidence of viral neuroinvasion. Patients recovered without sequelae. Hyperactivated cytokine response may play a role in pathogenesis.",2010 Jan,"['Lee, Nelson', 'Wong, Chun Kwok', 'Chan, Paul K.S.', 'Lindegardh, Niklas', 'White, Nicholas J.', 'Hayden, Frederick G.', 'Wong, Edward H.C.', 'Wong, Ka Shing', 'Cockram, Clive S.', 'Sung, Joseph J.Y.', 'Hui, David S.C.']",Emerg Infect Dis,,,True
0312582594429d880453377773c1925f5b65682b,PMC,"Recombinant Canine Coronaviruses in Dogs, Europe",http://dx.doi.org/10.3201/eid1601.090726,PMC2874359,20031041,NO-CC CODE,"Coronaviruses of potential recombinant origin with porcine transmissible gastroenteritis virus (TGEV), referred to as a new subtype (IIb) of canine coronavirus (CCoV), were recently identified in dogs in Europe. To assess the distribution of the TGEV-like CCoV subtype, during 2001–2008 we tested fecal samples from dogs with gastroenteritis. Of 1,172 samples, 493 (42.06%) were positive for CCoV. CCoV-II was found in 218 samples, and CCoV-I and CCoV-II genotypes were found in 182. Approximately 20% of the samples with CCoV-II had the TGEV-like subtype; detection rates varied according to geographic origin. The highest and lowest rates of prevalence for CCoV-II infection were found in samples from Hungary and Greece (96.87% and 3.45%, respectively). Sequence and phylogenetic analyses showed that the CCoV-IIb strains were related to prototype TGEV-like strains in the 5′ and the 3′ ends of the spike protein gene.",2010 Jan,"['Decaro, Nicola', 'Mari, Viviana', 'Elia, Gabriella', 'Addie, Diane D.', 'Camero, Michele', 'Lucente, Maria Stella', 'Martella, Vito', 'Buonavoglia, Canio']",Emerg Infect Dis,,,True
56e84cb19a30592280b4f0460ee74f8175eb98b3,PMC,"Laboratory Surge Response to Pandemic (H1N1) 2009 Outbreak, New York City Metropolitan Area, USA",http://dx.doi.org/10.3201/eid1601.091167,PMC2874380,20031036,NO-CC CODE,"The North Shore–Long Island Jewish Health System Laboratories serve 15 hospitals and affiliated regional physician practices in the New York City metropolitan area, with virus testing performed at a central reference laboratory. The influenza A pandemic (H1N1) 2009 outbreak began in this area on April 24, 2009, and within weeks respiratory virus testing increased 7.5 times. In response, laboratory and client service workforces were increased, physical plant build-out was completed, testing paradigms were converted from routine screening tests and viral culture to a high-capacity molecular assay for respiratory viruses, laboratory information system interfaces were built, and same-day epidemiologic reports were produced. Daily review by leadership of data from emergency rooms, hospital facilities, and the Health System Laboratories enabled real-time management of unfolding events. The ability of System laboratories to rapidly increase to high-volume comprehensive diagnostics, including influenza A subtyping, provided key epidemiologic information for local and state public health departments.",2010 Jan,"['Crawford, James M.', 'Stallone, Robert', 'Zhang, Fan', 'Gerolimatos, Mary', 'Korologos, Diamanto D.', 'Sweetapple, Carolyn', 'de Geronimo, Marcella', 'Dlugacz, Yosef', 'Armellino, Donna M.', 'Ginocchio, Christine C.']",Emerg Infect Dis,,,True
af80c32eafcea0399e640e11e913412f298e1aae,PMC,"Epidemiology of Travel-associated Pandemic (H1N1) 2009 Infection in 116 Patients, Singapore",http://dx.doi.org/10.3201/eid1601.091376,PMC2874386,20031038,NO-CC CODE,"In June 2009, during Singapore’s pandemic influenza plan containment phase, pandemic (H1N1) 2009 was introduced into the country through imported cases. To understand how travel patterns affected the initial outbreak, we examined epidemiologic and travel data for the first 116 case-patients admitted to Tan Tock Seng Hospital, Singapore, with travel-associated infection. Sixty-one percent and 54% of patients, respectively, met US Centers for Disease Control and Prevention and World Health Organization temperature criteria for influenza-like illness. One fourth of the case-patients traveled after illness onset, and 15% became ill while traveling. Regions of exposure for imported infections changed rapidly; case-patients initially arrived from North America, followed by Australasia and Southeast Asia. Case-patients on longer flights were more likely to become ill before arrival; those with shorter flights tended to become ill after arrival. Thermal scanners detected fevers in 12% of the arriving case-patients, resulting in a shorter time to isolation.",2010 Jan,"['Mukherjee, Pratik', 'Lim, Poh Lian', 'Chow, Angela', 'Barkham, Timothy', 'Seow, Eillyne', 'Win, Mar Kyaw', 'Chua, Arlene', 'Leo, Yee Sin', 'Chen, Mark I-Cheng']",Emerg Infect Dis,,,True
1531085b662c68caaedc8dc13d826759142d8829,PMC,10th Annual Conference on New and Re-emerging Infectious Diseases,http://dx.doi.org/10.3201/eid1311.070791,PMC2874435,,NO-CC CODE,,2007 Nov,"['Kitron, Uriel', 'Wilson, Brenda A.']",Emerg Infect Dis,,,False
516c3a32adbf893d696dec21d087c848b85b3940,PMC,The triage dilemma: opening Pandora's box... ever so slowly,http://dx.doi.org/10.1186/cc8215,PMC2875492,20092613,NO-CC CODE,,2010 Jan 19,"Burkle, Frederick M",Crit Care,,,True
e26317772e5eefc6c0ca5e616b2073c65c00550e,PMC,Clinical review: Critical care medicine in mainland China,http://dx.doi.org/10.1186/cc8222,PMC2875498,20236446,NO-CC CODE,"Critical care medicine began in mainland China in the early 1980s. After almost 30 years of effort, it has been recognized as a specialty very recently. However, limited data suggest that critical care resources, especially ICU beds, are inadequate compared with those of developed countries. National critical care societies work together to set up good practice standards, and to improve academic levels with scientific meetings, education programs, and training courses. Critical care research in mainland China is beginning to evolve, with great potential for improvement.",2010 Feb 25,"['Du, Bin', 'Xi, Xiuming', 'Chen, Dechang', 'Peng, Jinmin']",Crit Care,,,True
81bc3b72979ca17bc4385765f5e4452315d4b138,PMC,First evidence of a pro-inflammatory response to severe infection with influenza virus H1N1,http://dx.doi.org/10.1186/cc8846,PMC2875516,20236480,NO-CC CODE,"The great majority of infections caused by the pandemic variant of the influenza virus (nvH1N1) are self-limited, but a small percentage of patients develop severe symptoms requiring hospitalization. Bermejo-Martin and colleagues have presented a pilot study describing the differences in the early immune response for patients both mildly and severely infected with nvH1N1. Patients who develop severe symptoms after nvH1N1 infection showed Th1 and Th17 'hypercytokinemia', compared to mildly infected patients and healthy controls. The mediators involved with the Th1 and Th17 profiles are known to be involved in antiviral, pro-inflammatory and autoimmune responses. This is the first work reporting the association of a pro-inflamatory immune response with a severe pandemic infection, although it is likely that more studies are needed to understand the detrimental or beneficial roles these cytokines play in the evolution of mild and severe nvH1N1 infection.",2010 Feb 11,"['de Castro, Isabel Fernández', 'Guzmán-Fulgencio, María', 'García-Álvarez, Mónica', 'Resino, Salvador']",Crit Care,,,True
d34916b7408b3fc84c9cf4c9b4e50115cafcbd6f,PMC,Emerging Viruses in Human Populations,http://dx.doi.org/10.3201/eid1312.070794,PMC2876770,,NO-CC CODE,,2007 Dec,"Brault, Aaron C.",Emerg Infect Dis,,,False
0f78d742b7aec2eb129584fece81ac7628cc2648,PMC,"Clinical and Epidemiologic Characterization of WU Polyomavirus Infection, St. Louis, Missouri",http://dx.doi.org/10.3201/eid1312.070977,PMC2876771,18258052,NO-CC CODE,"WU polyomavirus is a recently described polyomavirus found in patients with respiratory infections. Of 2,637 respiratory samples tested in St. Louis, Missouri, 2.7% were positive for WU polyomavirus by PCR, and 71% were coinfected with other respiratory viruses. Persistent human infection with WU polyomavirus is described.",2007 Dec,"['Le, Binh-Minh', 'Demertzis, Lee M.', 'Wu, Guang', 'Tibbets, Robert J.', 'Buller, Richard', 'Arens, Max Q.', 'Gaynor, Anne M.', 'Storch, Gregory A.', 'Wang, David']",Emerg Infect Dis,,,False
ce4796d011abc721c271d969b7f3802e263a80b0,PMC,"Clinical and Epidemiologic Characterization of WU Polyomavirus Infection, St. Louis, Missouri",http://dx.doi.org/10.3201/eid1312.070977,PMC2876771,18258052,NO-CC CODE,"WU polyomavirus is a recently described polyomavirus found in patients with respiratory infections. Of 2,637 respiratory samples tested in St. Louis, Missouri, 2.7% were positive for WU polyomavirus by PCR, and 71% were coinfected with other respiratory viruses. Persistent human infection with WU polyomavirus is described.",2007 Dec,"['Le, Binh-Minh', 'Demertzis, Lee M.', 'Wu, Guang', 'Tibbets, Robert J.', 'Buller, Richard', 'Arens, Max Q.', 'Gaynor, Anne M.', 'Storch, Gregory A.', 'Wang, David']",Emerg Infect Dis,,,True
50c1901ebf4db31816c88cc4c2512ca0261730fb,PMC,"WU Polyomavirus in Children with Acute Lower Respiratory Tract Infections, South Korea",http://dx.doi.org/10.3201/eid1311.070872,PMC2878209,18217567,NO-CC CODE,"In South Korea, WU polyomavirus (WUPyV) was detected in 34 (7%) of 486 children with acute lower respiratory tract infections, 3 (4.2%) of 72 asymptomatic children, and as coinfection with other respiratory viruses in 23 (67.6%) children. Although WUPyV was frequently detected, its clinical role has not been distinguished from that of coinfecting viruses.",2007 Nov,"['Han, Tae Hee', 'Chung, Ju-Young', 'Koo, Ja Wook', 'Kim, Sang Woo', 'Hwang, Eung-Soo']",Emerg Infect Dis,,,True
50dd715b6dfd61f8b87474e37fb0817c14cd465f,PMC,Effects of Internal Border Control on Spread of Pandemic Influenza,http://dx.doi.org/10.3201/eid1307.060740,PMC2878213,18214176,NO-CC CODE,"We investigated the capacity of internal border control to limit influenza spread in an emergent pandemic in the context of Australia, a country with a low-population density and geopolitical boundaries that may facilitate restrictions. Mathematical models were used to study the time delay between epidemics in 2 population centers when travel restrictions were imposed. The models demonstrated that population size, travel rates, and places where travelers reside can strongly influence delay. The model simulations suggested that moderate delays in geographic spread may be possible with stringent restrictions and a low reproduction number, but results will be sensitive to the reproduction number and timing of restrictions. Model limitations include the absence of further importations and additional control measures. Internal border control may have a role in protecting domestic centers early in a pandemic, when importations are sparse. Our results may be useful for policymakers.",2007 Jul,"['Wood, James G.', 'Zamani, Nasim', 'MacIntyre, C. Raina', 'Becker, Niels G.']",Emerg Infect Dis,,,True
34bc96d247a78a804e014e09c997bf5f2ac71b6d,PMC,Effects of Internal Border Control on Spread of Pandemic Influenza,http://dx.doi.org/10.3201/eid1307.060740,PMC2878213,18214176,NO-CC CODE,"We investigated the capacity of internal border control to limit influenza spread in an emergent pandemic in the context of Australia, a country with a low-population density and geopolitical boundaries that may facilitate restrictions. Mathematical models were used to study the time delay between epidemics in 2 population centers when travel restrictions were imposed. The models demonstrated that population size, travel rates, and places where travelers reside can strongly influence delay. The model simulations suggested that moderate delays in geographic spread may be possible with stringent restrictions and a low reproduction number, but results will be sensitive to the reproduction number and timing of restrictions. Model limitations include the absence of further importations and additional control measures. Internal border control may have a role in protecting domestic centers early in a pandemic, when importations are sparse. Our results may be useful for policymakers.",2007 Jul,"['Wood, James G.', 'Zamani, Nasim', 'MacIntyre, C. Raina', 'Becker, Niels G.']",Emerg Infect Dis,,,True
a1533dacc01547792d22032e0781a7ea7632f0cb,PMC,Blood Screening for Influenza,http://dx.doi.org/10.3201/eid1307.060861,PMC2878216,18214186,NO-CC CODE,"Influenza viruses, including highly pathogenic avian influenza virus (H5N1), could threaten blood safety. We analyzed 10,272 blood donor samples with a minipool nucleic acid amplication technique. Analytical sensitivity of the method was 804 geq/mL and 444 geq/mL for generic influenza primers and influenza (H5N1) subtype–specific primers. This study demonstrates that such screening for influenza viruses is feasible.",2007 Jul,"['Hourfar, Michael Kai', 'Themann, Anna', 'Eickmann, Markus', 'Puthavathana, Pilaipan', 'Laue, Thomas', 'Seifried, Erhard', 'Schmidt, Michael']",Emerg Infect Dis,,,True
00534e81b57655bfaaad33a06b6d24015491a082,PMC,Person-to-Person Transmission of Nipah Virus in a Bangladeshi Community,http://dx.doi.org/10.3201/eid1307.061128,PMC2878219,18214175,NO-CC CODE,"An encephalitis outbreak was investigated in Faridpur District, Bangladesh, in April–May 2004 to determine the cause of the outbreak and risk factors for disease. Biologic specimens were tested for Nipah virus. Surfaces were evaluated for Nipah virus contamination by using reverse transcription–PCR (RT-PCR). Thirty-six cases of Nipah virus illness were identified; 75% of case-patients died. Multiple peaks of illness occurred, and 33 case-patients had close contact with another Nipah virus patient before their illness. Results from a case-control study showed that contact with 1 patient carried the highest risk for infection (odds ratio 6.7, 95% confidence interval 2.9–16.8, p<0.001). RT-PCR testing of environmental samples confirmed Nipah virus contamination of hospital surfaces. This investigation provides evidence for person-to-person transmission of Nipah virus. Capacity for person-to-person transmission increases the potential for wider spread of this highly lethal pathogen and highlights the need for infection control strategies for resource-poor settings.",2007 Jul,"['Gurley, Emily S.', 'Montgomery, Joel M.', 'Hossain, M. Jahangir', 'Bell, Michael', 'Azad, Abul Kalam', 'Islam, Mohammed Rafiqul', 'Molla, Mohammed Abdur Rahim', 'Carroll, Darin S.', 'Ksiazek, Thomas G.', 'Rota, Paul A.', 'Lowe, Luis', 'Comer, James A.', 'Rollin, Pierre', 'Czub, Markus', 'Grolla, Allen', 'Feldmann, Heinz', 'Luby, Stephen P.', 'Woodward, Jennifer L.', 'Breiman, Robert F.']",Emerg Infect Dis,,,False
93449583723d3c74095362edbb236d263cf83821,PMC,Person-to-Person Transmission of Nipah Virus in a Bangladeshi Community,http://dx.doi.org/10.3201/eid1307.061128,PMC2878219,18214175,NO-CC CODE,"An encephalitis outbreak was investigated in Faridpur District, Bangladesh, in April–May 2004 to determine the cause of the outbreak and risk factors for disease. Biologic specimens were tested for Nipah virus. Surfaces were evaluated for Nipah virus contamination by using reverse transcription–PCR (RT-PCR). Thirty-six cases of Nipah virus illness were identified; 75% of case-patients died. Multiple peaks of illness occurred, and 33 case-patients had close contact with another Nipah virus patient before their illness. Results from a case-control study showed that contact with 1 patient carried the highest risk for infection (odds ratio 6.7, 95% confidence interval 2.9–16.8, p<0.001). RT-PCR testing of environmental samples confirmed Nipah virus contamination of hospital surfaces. This investigation provides evidence for person-to-person transmission of Nipah virus. Capacity for person-to-person transmission increases the potential for wider spread of this highly lethal pathogen and highlights the need for infection control strategies for resource-poor settings.",2007 Jul,"['Gurley, Emily S.', 'Montgomery, Joel M.', 'Hossain, M. Jahangir', 'Bell, Michael', 'Azad, Abul Kalam', 'Islam, Mohammed Rafiqul', 'Molla, Mohammed Abdur Rahim', 'Carroll, Darin S.', 'Ksiazek, Thomas G.', 'Rota, Paul A.', 'Lowe, Luis', 'Comer, James A.', 'Rollin, Pierre', 'Czub, Markus', 'Grolla, Allen', 'Feldmann, Heinz', 'Luby, Stephen P.', 'Woodward, Jennifer L.', 'Breiman, Robert F.']",Emerg Infect Dis,,,False
057e31ee37a66543d6cf7f189356b43deb91a31a,PMC,Person-to-Person Transmission of Nipah Virus in a Bangladeshi Community,http://dx.doi.org/10.3201/eid1307.061128,PMC2878219,18214175,NO-CC CODE,"An encephalitis outbreak was investigated in Faridpur District, Bangladesh, in April–May 2004 to determine the cause of the outbreak and risk factors for disease. Biologic specimens were tested for Nipah virus. Surfaces were evaluated for Nipah virus contamination by using reverse transcription–PCR (RT-PCR). Thirty-six cases of Nipah virus illness were identified; 75% of case-patients died. Multiple peaks of illness occurred, and 33 case-patients had close contact with another Nipah virus patient before their illness. Results from a case-control study showed that contact with 1 patient carried the highest risk for infection (odds ratio 6.7, 95% confidence interval 2.9–16.8, p<0.001). RT-PCR testing of environmental samples confirmed Nipah virus contamination of hospital surfaces. This investigation provides evidence for person-to-person transmission of Nipah virus. Capacity for person-to-person transmission increases the potential for wider spread of this highly lethal pathogen and highlights the need for infection control strategies for resource-poor settings.",2007 Jul,"['Gurley, Emily S.', 'Montgomery, Joel M.', 'Hossain, M. Jahangir', 'Bell, Michael', 'Azad, Abul Kalam', 'Islam, Mohammed Rafiqul', 'Molla, Mohammed Abdur Rahim', 'Carroll, Darin S.', 'Ksiazek, Thomas G.', 'Rota, Paul A.', 'Lowe, Luis', 'Comer, James A.', 'Rollin, Pierre', 'Czub, Markus', 'Grolla, Allen', 'Feldmann, Heinz', 'Luby, Stephen P.', 'Woodward, Jennifer L.', 'Breiman, Robert F.']",Emerg Infect Dis,,,True
91d05ee767e5582b61781844a76f08951ce43501,PMC,"Influenza Pandemics in Singapore, a Tropical, Globally Connected City",http://dx.doi.org/10.3201/eid1307.061313,PMC2878222,18214178,NO-CC CODE,"Tropical cities such as Singapore do not have well-defined influenza seasons but have not been spared from influenza pandemics. The 1918 epidemic in Singapore, which was then already a major global trading hub, occurred in 2 waves, June–July, and October–November, and resulted in >2,870 deaths. The excess mortality rate was higher than that for industrialized nations in the Northern Hemisphere but lower than that for less industrialized countries in Asia and Africa. The 1957 epidemic occurred in May and resulted in widespread illness. The 1968 epidemic occurred in August and lasted a few weeks, again with widespread illness. Tropical cities may be affected early in a pandemic and have higher mortality rates. With the increase in travel and trade, a future pandemic may reach a globally connected city early and spread worldwide. Preparedness and surveillance plans must be developed to include the megacities of the tropical world.",2007 Jul,"['Lee, Vernon J.', 'Chen, Mark I.', 'Chan, Siew Pang', 'Wong, Chia Siong', 'Cutter, Jeffery', 'Goh, Kee Tai', 'Tambyah, Paul Anath']",Emerg Infect Dis,,,True
3a6a9f669d1d3bf1880190cd747efed573dc5dab,PMC,"Human Influenza A (H5N1) Cases, Urban Areas of People’s Republic of China, 2005–2006",http://dx.doi.org/10.3201/eid1307.061557,PMC2878233,18214180,NO-CC CODE,"We investigated potential sources of infection for 6 confirmed influenza A (H5N1) patients who resided in urban areas of People’s Republic of China. None had known exposure to sick poultry or poultry that died from illness, but all had visited wet poultry markets before illness.",2007 Jul,"['Yu, Hongjie', 'Feng, Zijian', 'Zhang, Xianfeng', 'Xiang, Nijuan', 'Huai, Yang', 'Zhou, Lei', 'Li, Zhongjie', 'Xu, Cuiling', 'Luo, Huiming', 'He, Jianfeng', 'Guan, Xuhua', 'Yuan, Zhengan', 'Li, Yanting', 'Xu, Longshan', 'Hong, Rongtao', 'Liu, Xuecheng', 'Zhou, Xingyu', 'Yin, Wenwu', 'Zhang, Shunxiang', 'Shu, Yuelong', 'Wang, Maowu', 'Wang, Yu', 'Lee, Chin-Kei', 'Uyeki, Timothy M.', 'Yang, Weizhong', None]",Emerg Infect Dis,,,True
aa8016f871841b6899dac58441f6f8de93f30ffa,PMC,Cytokine profiles of suction pulmonary secretions from children infected with pandemic influenza A(H1N1) 2009,http://dx.doi.org/10.1186/cc8918,PMC2887147,20416119,NO-CC CODE,,2010 Apr 13,"['Kawashima, Hisashi', 'Go, Soken', 'Kashiwagi, Yasuyo', 'Morishima, Yasuyuki', 'Miura, Taro', 'Ushio, Masanobu', 'Nishimata, Shigeo', 'Takekuma, Kouji']",Crit Care,,,True
e6c4b7349bd9542b2aa4a58acc26c5a6adaf4ba0,PMC,On computational approaches for size-and-shape distributions from sedimentation velocity analytical ultracentrifugation,http://dx.doi.org/10.1007/s00249-009-0545-7,PMC2892069,19806353,NO-CC CODE,"Sedimentation velocity analytical ultracentrifugation has become a very popular technique to study size distributions and interactions of macromolecules. Recently, a method termed two-dimensional spectrum analysis (2DSA) for the determination of size-and-shape distributions was described by Demeler and colleagues (Eur Biophys J 2009). It is based on novel ideas conceived for fitting the integral equations of the size-and-shape distribution to experimental data, illustrated with an example but provided without proof of the principle of the algorithm. In the present work, we examine the 2DSA algorithm by comparison with the mathematical reference frame and simple well-known numerical concepts for solving Fredholm integral equations, and test the key assumptions underlying the 2DSA method in an example application. While the 2DSA appears computationally excessively wasteful, key elements also appear to be in conflict with mathematical results. This raises doubts about the correctness of the results from 2DSA analysis.",2010 Jul 6,"Schuck, Peter",Eur Biophys J,,,True
b31b7e11a6cf05cf0132d92bc09ee5911e7672f0,PMC,Using Complementary and Alternative Medicines to Target the Host Response during Severe Influenza,http://dx.doi.org/10.1093/ecam/nep152,PMC2892358,19779008,NO-CC CODE,"It is now accepted that an overwhelming inflammatory response is the cause of human deaths from avian H5N1 influenza infection. With this in mind we sought to examine the literature for examples of complementary and alternative medicines that reduce inflammation, and to place the results of this search in the context of our own work in a mouse model of influenza disease, using a pharmaceutical agent with anti-inflammatory properties. Two Chinese herbs, Angelica sinensis (Dang Gui) and Salvia miltiorrhiza (Danshen), have been recently shown to protect mice during lethal experimental sepsis via inhibition of the novel inflammatory cytokine High Mobility Group Box 1 protein (HMGB1). Biochanin A, a ligand of the peroxisome proliferator activated receptors (PPAR) alpha and gamma and the active isoflavone in Trifolium pratense (red clover), has anti-inflammatory properties, and thus could be used as an influenza treatment. This is of great interest since we have recently shown that gemfibrozil, a drug used to treat hyperlipidemia in humans and a synthetic ligand of PPAR alpha, significantly reduces the mortality associated with influenza infections in mice. The inflammation-modulating abilities of these natural agents should be considered in light of what is now known about the mechanisms of fatal influenza, and tested as potential candidates for influenza treatments in their own right, or as adjunct treatments to antivirals.",2010 Dec 24,"['Alleva, Lisa M.', 'Cai, Charles', 'Clark, Ian A.']",Evid Based Complement Alternat Med,,,True
803f7053c2a6c053e0ebcd748c6a0f2462a5c067,PMC,Trypsin Isoinhibitors with Antiproliferative Activity toward Leukemia Cells from Phaseolus vulgaris cv “White Cloud Bean”,http://dx.doi.org/10.1155/2010/219793,PMC2896657,20617140,NO-CC CODE,"A purification protocol that comprised ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose, and gel filtration by FPLC on Superdex 75 was complied to isolate two trypsin inhibitors from Phaseolus vulgaris cv “White Cloud Bean”. Both trypsin inhibitors exhibited a molecular mass of 16 kDa and reduced the activity of trypsin with an IC(50) value of about 0.6 μM. Dithiothreitol attenuated the trypsin inhibitory activity, signifying that an intact disulfide bond is indispensable to the activity. [Methyl-(3)H] thymidine incorporation by leukemia L1210 cells was inhibited with an IC(50) value of 28.8 μM and 21.5 μM, respectively. They were lacking in activity toward lymphoma MBL2 cells and inhibitory effect on HIV-1 reverse transcriptase and fungal growth when tested up to 100 μM.",2010 Jun 14,"['Sun, Jian', 'Wang, Hexiang', 'Ng, Tzi Bun']",J Biomed Biotechnol,,,True
7871f62facbecd9f3a12f4278c7aefaaec8899d6,PMC,Comparative Pathogenesis and Systems Biology for  Biodefense Virus Vaccine Development,http://dx.doi.org/10.1155/2010/236528,PMC2896660,20617142,NO-CC CODE,"Developing vaccines to biothreat agents presents a number of challenges for discovery, preclinical development, and licensure. The need for high containment to work with live agents limits the amount and types of research that can be done using complete pathogens, and small markets reduce potential returns for industry. However, a number of tools, from comparative pathogenesis of viral strains at the molecular level to novel computational approaches, are being used to understand the basis of viral attenuation and characterize protective immune responses. As the amount of basic molecular knowledge grows, we will be able to take advantage of these tools not only to rationally attenuate virus strains for candidate vaccines, but also to assess immunogenicity and safety in silico. This review discusses how a basic understanding of pathogenesis, allied with systems biology and machine learning methods, can impact biodefense vaccinology.",2010 Jun 6,"['Bowick, Gavin C.', 'Barrett, Alan D. T.']",J Biomed Biotechnol,,,True
30175004a6a58f006a53f32c00e0363c126f667b,PMC,Oral Vaccination with the Porcine Rotavirus VP4 Outer Capsid Protein Expressed by Lactococcus lactis Induces Specific Antibody Production,http://dx.doi.org/10.1155/2010/708460,PMC2896853,20625406,NO-CC CODE,"The objective of this study to design a delivery system resistant to the gastrointestinal environment for oral vaccine against porcine rotavirus. Lactococcus lactis NZ9000 was transformed with segments of vP4 of the porcine rotavirus inserted into the pNZ8112 surface-expression vector, and a recombinant L. lactis expressing VP4 protein was constructed. An approximately 27 kDa VP4 protein was confirmed by SDS-PAGE , Western blot and immunostaining analysis. BALB/c mice were immunized orally with VP4-expression recombinant L. lactis and cellular, mucosal and systemic humoral immune responses were examined. Specific anti-VP4 secretory IgA and IgG were found in feces, ophthalmic and vaginal washes and in serum. The induced antibodies demonstrated neutralizing effects on porcine rotavirus infection on MA104 cells. Our findings suggest that oral immunization with VP4-expressing L. lactis induced both specific local and systemic humoral and cellular immune responses in mice.",2010 Jun 6,"['Li, Yi-jing', 'Ma, Guang-peng', 'Li, Gui-wei', 'Qiao, Xin-yuan', 'Ge, Jun-wei', 'Tang, Li-jie', 'Liu, Min', 'Liu, Li-wei']",J Biomed Biotechnol,,,True
230a3e80afacb1c6a06912b5ad06df56fc4535b2,PMC,Rate of Compliance with Hand Hygiene by Dental Healthcare Personnel (DHCP) within a Dentistry Healthcare First Aid Facility,,PMC2897854,20613909,NO-CC CODE,"OBJECTIVES: To evaluate the compliance with the opportunities of hand hygiene by dentistry school healthcare professionals, as well as the higher choice products. METHODS: Through direct observation, the oral healthcare team-professors, oral and maxillofacial surgery residents, graduation students-for daily care were monitored: before performing the first treatment of the shift, after snacks and meals, and after going to the bathroom (initial opportunities) as well as between patients’ care, and after ending the shift (following opportunities). RESULTS: The professors’ category profited 78.4% of all opportunities while residents and graduation students did not reach 50.0% of compliance. Statistically significant data (P≤.05) were seen between categories: professors and residents, professors and graduation students, and between genders within the residents’ category. When opportunities were profited, the preferred choice for hand hygiene was water and soap (82.2%), followed by 70% alcohol (10.2%), and both (7.6%). CONCLUSIONS: Although gloves were worn in all procedures, we concluded that the hygiene compliance by these professionals was under the expectation.",2010 Jul,"['de Amorim-Finzi, Marcília Batista', 'Cury, Mauro Vieira Cezar', 'Costa, Cláudio Rodrigues R.', 'dos Santos, Angelis Costa', 'de Melo, Geraldo Batista']",Eur J Dent,,,True
1a537a4d664e3ee6f53bbb7566e4837f31945b8d,PMC,Viral Infection Triggers Central Nervous System Autoimmunity Via Activation of Dual TCR-Expressing CD8(+) T Cells,http://dx.doi.org/10.1038/ni.1888,PMC2900379,20526343,NO-CC CODE,"Multiple sclerosis (MS) is an inflammatory, demyelinating, central nervous system disease mediated by myelin-specific T cells. Environmental triggers that cause a breakdown of myelin-specific T cell tolerance are unknown. We found that CD8(+) myelin basic protein (MBP)-specific T cell tolerance can be broken and autoimmunity induced by infection with a virus that does not express MBP cross-reactive epitopes and does not depend on bystander activation. Instead, the virus activated dual T cell receptor (TCR)-expressing T cells capable of recognizing both MBP and viral antigens. These results demonstrate the importance of dual TCR T cells in autoimmunity and suggest a mechanism by which a ubiquitous viral infection could trigger autoimmunity in a subset of infected individuals, as hypothesized in the etiology of MS.",2010 Jul 6,"['Ji, Qingyong', 'Perchellet, Antoine', 'Goverman, Joan M.']",Nat Immunol,,,True
ad3d8fb68b470597542e0f551b99ec9b880ab31e,PMC,Viral Infection Triggers Central Nervous System Autoimmunity Via Activation of Dual TCR-Expressing CD8(+) T Cells,http://dx.doi.org/10.1038/ni.1888,PMC2900379,20526343,NO-CC CODE,"Multiple sclerosis (MS) is an inflammatory, demyelinating, central nervous system disease mediated by myelin-specific T cells. Environmental triggers that cause a breakdown of myelin-specific T cell tolerance are unknown. We found that CD8(+) myelin basic protein (MBP)-specific T cell tolerance can be broken and autoimmunity induced by infection with a virus that does not express MBP cross-reactive epitopes and does not depend on bystander activation. Instead, the virus activated dual T cell receptor (TCR)-expressing T cells capable of recognizing both MBP and viral antigens. These results demonstrate the importance of dual TCR T cells in autoimmunity and suggest a mechanism by which a ubiquitous viral infection could trigger autoimmunity in a subset of infected individuals, as hypothesized in the etiology of MS.",2010 Jul 6,"['Ji, Qingyong', 'Perchellet, Antoine', 'Goverman, Joan M.']",Nat Immunol,,,False
ed41111b7ec211ae5ad254835306b8a92567411d,PMC,A Mechanism of Virus-Induced Demyelination,http://dx.doi.org/10.1155/2010/109239,PMC2905936,20652053,NO-CC CODE,"Myelin forms an insulating sheath surrounding axons in the central and peripheral nervous systems and is essential for rapid propagation of neuronal action potentials. Demyelination is an acquired disorder in which normally formed myelin degenerates, exposing axons to the extracellular environment. The result is dysfunction of normal neuron-to-neuron communication and in many cases, varying degrees of axonal degeneration. Numerous central nervous system demyelinating disorders exist, including multiple sclerosis. Although demyelination is the major manifestation of most of the demyelinating diseases, recent studies have clearly documented concomitant axonal loss to varying degrees resulting in long-term disability. Axonal injury may occur secondary to myelin damage (outside-in model) or myelin damage may occur secondary to axonal injury (inside-out model). Viral induced demyelination models, has provided unique imminent into the cellular mechanisms of myelin destruction. They illustrate mechanisms of viral persistence, including latent infections, virus reactivation and viral-induced tissue damage. These studies have also provided excellent paradigms to study the interactions between the immune system and the central nervous system (CNS). In this review we will discuss potential cellular and molecular mechanism of central nervous system axonal loss and demyelination in a viral induced mouse model of multiple sclerosis.",2010 Jun 21,"Das Sarma, Jayasri",Interdiscip Perspect Infect Dis,,,True
1c38d6ab050242d8a1552846481949dc6aa75690,PMC,Distinctive clinical features of human bocavirus in children younger than 2 years,http://dx.doi.org/10.1007/s00431-010-1183-x,PMC2908446,20383526,NO-CC CODE,"BACKGROUND AND OBJECTIVE: Clinical characteristics of human bocavirus (HBoV) infection have been studied worldwide, but their importance of those characteristics remains unknown. We investigated distinctive clinical features of HBoV-positive children with lower respiratory tract infection (LRTI). METHODS AND RESULTS: During April 2007–July 2009, for 402 hospitalized children younger than 2 years with LRTI, we prospectively examined virus genomes in nasopharyngeal swabs for HBoV, respiratory syncytial virus (RSV), rhinovirus, metapneumovirus, parainfluenzavirus, and adenovirus. The HBoV genomes were identified in 34 patients (8.5%). Clinical and laboratory data of HBoV-positive and other virus/bacteria-negative patients (n = 18) were analyzed and compared with data of RSV-single positive patients (n = 99). The seasonal distribution of HBoV exhibits a concentration of cases during March–September, with most RSV cases occurring during winter in Japan. The minimum age of HBoV-positive patients was 5 months, although 44 patients (44%) with RSV were younger than 6 months. The main clinical features were respiratory distress and hypoxia. Hypoxia advances within 3 days after onset. The mean oxygen saturation on arrival was 92.8%, which was significantly lower than that in patients with RSV (p < 0.001). White blood cell counts were similar among groups. However, the percentage of neutrophils in white blood cells were significantly higher in HBoV-positive patients (62 vs. 45%, p < 0.001). Their prognoses were good. Their hospital stays were 6.6 days. CONCLUSIONS: HBoV-single positive patients show several clinical characteristics, such as seasonality, age, hypoxia, and neutrophilia, which differ from those with RSV infection.",2010 Sep 10,"['Moriyama, Yoko', 'Hamada, Hiromichi', 'Okada, Mineyuki', 'Tsuchiya, Nozomi', 'Maru, Hiromi', 'Shirato, Yuri', 'Maeda, Yasuhiro', 'Hirose, Yosuke', 'Yoshida, Masaki', 'Omura, Yoh', 'Honda, Takafumi', 'Muto, Ayako', 'Hayashi, Kitami', 'Terai, Masaru']",Eur J Pediatr,,,True
41ff8966b05ab778bb135d48143800f2792807fa,PMC,Vaxign: The First Web-Based Vaccine Design Program for Reverse Vaccinology and Applications for Vaccine Development,http://dx.doi.org/10.1155/2010/297505,PMC2910479,20671958,NO-CC CODE,"Vaxign is the first web-based vaccine design system that predicts vaccine targets based on genome sequences using the strategy of reverse vaccinology. Predicted features in the Vaxign pipeline include protein subcellular location, transmembrane helices, adhesin probability, conservation to human and/or mouse proteins, sequence exclusion from genome(s) of nonpathogenic strain(s), and epitope binding to MHC class I and class II. The precomputed Vaxign database contains prediction of vaccine targets for >70 genomes. Vaxign also performs dynamic vaccine target prediction based on input sequences. To demonstrate the utility of this program, the vaccine candidates against uropathogenic Escherichia coli (UPEC) were predicted using Vaxign and compared with various experimental studies. Our results indicate that Vaxign is an accurate and efficient vaccine design program.",2010 Jul 4,"['He, Yongqun', 'Xiang, Zuoshuang', 'Mobley, Harry L. T.']",J Biomed Biotechnol,,,True
cf2af5e2c7b504fe693f5d5a70c42bf97ed4faec,PMC,The efficacy of herbal therapy on quality of life in patients with breast cancer: self-control clinical trial,,PMC2915555,20694182,NO-CC CODE,"BACKGROUND: Mounting evidence indicates that herbal therapy is effective in alleviating anxiety, lessening cancer treatment-related side-effects, and facilitating rehabilitation. This is the first trial to examine the herbal therapy of combined yunzhi and danshen on quality of life among breast cancer patients. METHODS: A multicenter, longitudinal, and self-control study was used. Eighty-two breast cancer patients were given combined yunzhi and danshen capsules for six months on a daily basis. Data collection including quality of life, vitality status and adverse effects were taken. RESULTS: Results showed a significant improvement in physical function, role-physical, role-emotion and health transition (P < 0.05). Patients also reported less fatigue, better quality of sleep, better appetite, more regular bowel movements and more stable emotions (P < 0.05). As far as side-effects were concerned, only mild discomforts including sore throat (13.4%) and dry mouth (9.8%) were recorded. CONCLUSION: The findings add clinical evidence to support the beneficial effects of herbal therapy on quality of life and vitality status in breast cancer patients. Therefore, herbal therapy has a potentially important role to play in managing psychological distress in cancer patients. This study also suggests that herbal therapy is clinically acceptable and can be used safely with breast cancer patients.",2010 Jul 21,"['Wong, Lai Yi Eliza', 'Wong, Chun Kwok', 'Leung, Ping Chung', 'Lam, Wei Kei Christopher']",Patient Prefer Adherence,,,True
7b5f035fa37b84d80757e91805bdb1dc470f3f7c,PMC,Structural basis for receptor recognition by New World hemorrhagic fever arenaviruses,http://dx.doi.org/10.1038/nsmb.1772,PMC2920743,20208545,NO-CC CODE,New World (NW) hemorrhagic fever arenaviruses are rodent-borne agents that cause severe human disease. The GP1 subunit of the surface glycoprotein (GP) mediates cell attachment through transferrin receptor 1 (TfR1). We report the structure of Machupo virus (MACV) GP1 bound with human TfR1. Atomic details of the GP1:TfR1 interface clarify the importance of TfR1 residues implicated in NW arenavirus host specificity. Analysis of sequence variation among NW arenavirus GP1s and their host-species receptors in light of the molecular structure indicates determinants of viral zoonotic transmission. Infectivities of pseudoviruses in cells expressing mutated TfR1 confirm that contacts at the tip of the TfR1 apical domain determine the capacity of human TfR1 to mediate infection by particular NW arenaviruses. We propose that NW arenaviruses pathogenic to humans fortuitously acquired affinity for human TfR1 during adaptation to TfR1 of their natural hosts.,2010 Apr 7,"['Abraham, Jonathan', 'Corbett, Kevin D.', 'Farzan, Michael', 'Choe, Hyeryun', 'Harrison, Stephen C.']",Nat Struct Mol Biol,,,True
0c4b19d02fd4fad087f3571c64cc5c33dcb5a3fb,PMC,Structural basis for receptor recognition by New World hemorrhagic fever arenaviruses,http://dx.doi.org/10.1038/nsmb.1772,PMC2920743,20208545,NO-CC CODE,New World (NW) hemorrhagic fever arenaviruses are rodent-borne agents that cause severe human disease. The GP1 subunit of the surface glycoprotein (GP) mediates cell attachment through transferrin receptor 1 (TfR1). We report the structure of Machupo virus (MACV) GP1 bound with human TfR1. Atomic details of the GP1:TfR1 interface clarify the importance of TfR1 residues implicated in NW arenavirus host specificity. Analysis of sequence variation among NW arenavirus GP1s and their host-species receptors in light of the molecular structure indicates determinants of viral zoonotic transmission. Infectivities of pseudoviruses in cells expressing mutated TfR1 confirm that contacts at the tip of the TfR1 apical domain determine the capacity of human TfR1 to mediate infection by particular NW arenaviruses. We propose that NW arenaviruses pathogenic to humans fortuitously acquired affinity for human TfR1 during adaptation to TfR1 of their natural hosts.,2010 Apr 7,"['Abraham, Jonathan', 'Corbett, Kevin D.', 'Farzan, Michael', 'Choe, Hyeryun', 'Harrison, Stephen C.']",Nat Struct Mol Biol,,,True
9eab3344aca02a78b6a81ebda1666faff0561e39,PMC,"Spatial Distribution of Diarrhoea and Microbial Quality of Domestic Water during an Outbreak of Diarrhoea in the Tshikuwi Community in Venda, South Africa",,PMC2928092,19902801,NO-CC CODE,"Total microbial quality assessment and geographical information system were used for evaluating the quality of water and the spatial distribution of diarrhoea cases in Tshikuwi, a rural community in South Africa, during an outbreak of diarrhoea. The water-abstraction points included two groundwater storage tanks, namely Tank 1 and Tank 2 and the Khandanama river. Indicator microbial counts for total coliforms, faecal coliforms, enterococci, and heterotrophic bacteria exceeded the limit for no risk as stipulated by the South African water-quality guidelines for domestic use for Tank 1 and the Khandanama river. Vibrio, Salmonella, and Shigella species were prevalent in the Khandanama river. The spatial distribution of diarrhoea cases showed a hot-spot of diarrhoea cases close to Tank 1 and the Khandanama river. Results of chi-square analysis showed that the proportion of infection from each water source was different or that infection depends on the type of water source (α=0.05). The demonstrated spatial clustering of diarrhoea cases might have been influenced by the poor microbial quality of water used from Tank 1 and the Khandanama river. The results further highlight the urgent need of water-treatment facilities and monitoring of water quality in rural communities of South Africa.",2009 Oct,"['Bessong, Pascal O.', 'Odiyo, John O.', 'Musekene, Justice N.', 'Tessema, Abera']",J Health Popul Nutr,,,True
2e2bc679c8393230bac2af64115bab7ed1ba62c0,PMC,Large-scale implementation of a critical care surge capacity management program,http://dx.doi.org/10.1186/cc8514,PMC2934227,,NO-CC CODE,,2010 Mar 1,"['Lawless, BW', 'Trpkovski, J']",Crit Care,,,True
75ebad1e8641e5fe2a51214f4d97742ab59a8dae,PMC,Air pollution and case fatality of SARS in the People's Republic of China: an ecologic study,http://dx.doi.org/10.1186/1476-069X-2-15,PMC293432,14629774,NO-CC CODE,"BACKGROUND: Severe acute respiratory syndrome (SARS) has claimed 349 lives with 5,327 probable cases reported in mainland China since November 2002. SARS case fatality has varied across geographical areas, which might be partially explained by air pollution level. METHODS: Publicly accessible data on SARS morbidity and mortality were utilized in the data analysis. Air pollution was evaluated by air pollution index (API) derived from the concentrations of particulate matter, sulfur dioxide, nitrogen dioxide, carbon monoxide and ground-level ozone. Ecologic analysis was conducted to explore the association and correlation between air pollution and SARS case fatality via model fitting. Partially ecologic studies were performed to assess the effects of long-term and short-term exposures on the risk of dying from SARS. RESULTS: Ecologic analysis conducted among 5 regions with 100 or more SARS cases showed that case fatality rate increased with the increment of API (case fatality = - 0.063 + 0.001 * API). Partially ecologic study based on short-term exposure demonstrated that SARS patients from regions with moderate APIs had an 84% increased risk of dying from SARS compared to those from regions with low APIs (RR = 1.84, 95% CI: 1.41–2.40). Similarly, SARS patients from regions with high APIs were twice as likely to die from SARS compared to those from regions with low APIs. (RR = 2.18, 95% CI: 1.31–3.65). Partially ecologic analysis based on long-term exposure to ambient air pollution showed the similar association. CONCLUSION: Our studies demonstrated a positive association between air pollution and SARS case fatality in Chinese population by utilizing publicly accessible data on SARS statistics and air pollution indices. Although ecologic fallacy and uncontrolled confounding effect might have biased the results, the possibility of a detrimental effect of air pollution on the prognosis of SARS patients deserves further investigation.",2003 Nov 20,"['Cui, Yan', 'Zhang, Zuo-Feng', 'Froines, John', 'Zhao, Jinkou', 'Wang, Hua', 'Yu, Shun-Zhang', 'Detels, Roger']",Environ Health,,,True
777328a5bc26d551df06e62b64682c03c25dde03,PMC,Dendritic Cell-Specific Antigen Delivery by Coronavirus Vaccine Vectors Induces Long-Lasting Protective Antiviral and Antitumor Immunity,http://dx.doi.org/10.1128/mBio.00171-10,PMC2939679,20844609,NO-CC CODE,"Efficient vaccination against infectious agents and tumors depends on specific antigen targeting to dendritic cells (DCs). We report here that biosafe coronavirus-based vaccine vectors facilitate delivery of multiple antigens and immunostimulatory cytokines to professional antigen-presenting cells in vitro and in vivo. Vaccine vectors based on heavily attenuated murine coronavirus genomes were generated to express epitopes from the lymphocytic choriomeningitis virus glycoprotein, or human Melan-A, in combination with the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). These vectors selectively targeted DCs in vitro and in vivo resulting in vector-mediated antigen expression and efficient maturation of DCs. Single application of only low vector doses elicited strong and long-lasting cytotoxic T-cell responses, providing protective antiviral and antitumor immunity. Furthermore, human DCs transduced with Melan-A-recombinant human coronavirus 229E efficiently activated tumor-specific CD8(+) T cells. Taken together, this novel vaccine platform is well suited to deliver antigens and immunostimulatory cytokines to DCs and to initiate and maintain protective immunity.",2010 Sep 14,"['Cervantes-Barragan, Luisa', 'Züst, Roland', 'Maier, Reinhard', 'Sierro, Sophie', 'Janda, Jozef', 'Levy, Frederic', 'Speiser, Daniel', 'Romero, Pedro', 'Rohrlich, Pierre-Simon', 'Ludewig, Burkhard', 'Thiel, Volker']",mBio,,,True
2a664c1411e75f9237a896f1a9e120046438586d,PMC,Pathogenic characteristics of persistent feline enteric coronavirus infection in cats,http://dx.doi.org/10.1051/vetres/2010043,PMC2939696,20663472,NO-CC CODE,"Feline coronaviruses (FCoV) comprise two biotypes: feline enteric coronaviruses (FECV) and feline infectious peritonitis viruses (FIPV). FECV is associated with asymptomatic persistent enteric infections, while FIPV causes feline infectious peritonitis (FIP), a usually fatal systemic disease in domestic cats and some wild Felidae. FIPV arises from FECV by mutation. FCoV also occur in two serotypes, I and II, of which the serotype I viruses are by far the most prevalent in the field. Yet, most of our knowledge about FCoV infections relates to serotype II viruses, particularly about the FIPV, mainly because type I viruses grow poorly in cell culture. Hence, the aim of the present work was the detailed study of the epidemiologically most relevant viruses, the avirulent serotype I viruses. Kittens were inoculated oronasally with different doses of two independent FECV field strains, UCD and RM. Persistent infection could be reproducibly established. The patterns of clinical symptoms, faecal virus shedding and seroconversion were monitored for up to 10 weeks revealing subtle but reproducible differences between the two viruses. Faecal virus, i.e. genomic RNA, was detected during persistent FECV infection only in the large intestine, downstream of the appendix, and could occasionally be observed also in the blood. The implications of our results, particularly our insights into the persistently infected state, are discussed.",2010 Jul 23 Sep-Oct,"['Vogel, Liesbeth', 'Van der Lubben, Mariken', 'Te Lintelo, Eddie G.', 'Bekker, Cornelis P.J.', 'Geerts, Tamara', 'Schuijff, Leontine S.', 'Grinwis, Guy C.M.', 'Egberink, Herman F.', 'Rottier, Peter J.M.']",Vet Res,,,True
8c593d726094e8a047376050bd28806e371a2797,PMC,"Proteomics: Challenges, Techniques and Possibilities to Overcome Biological Sample Complexity",http://dx.doi.org/10.4061/2009/239204,PMC2950283,20948568,NO-CC CODE,"Proteomics is the large-scale study of the structure and function of proteins in complex biological sample. Such an approach has the potential value to understand the complex nature of the organism. Current proteomic tools allow large-scale, high-throughput analyses for the detection, identification, and functional investigation of proteome. Advances in protein fractionation and labeling techniques have improved protein identification to include the least abundant proteins. In addition, proteomics has been complemented by the analysis of posttranslational modifications and techniques for the quantitative comparison of different proteomes. However, the major limitation of proteomic investigations remains the complexity of biological structures and physiological processes, rendering the path of exploration paved with various difficulties and pitfalls. The quantity of data that is acquired with new techniques places new challenges on data processing and analysis. This article provides a brief overview of currently available proteomic techniques and their applications, followed by detailed description of advantages and technical challenges. Some solutions to circumvent technical difficulties are proposed.",2009 Dec 8,"['Chandramouli, Kondethimmanahalli', 'Qian, Pei-Yuan']",Hum Genomics Proteomics,,,True
cc2e7594049d91279f4e3d69d27b440ddd8de1f9,PMC,Bronchiolitis Obliterans Organizing Pneumonia in Swine Associated with Porcine Circovirus Type 2 Infection,http://dx.doi.org/10.1155/2011/245728,PMC2952812,20976305,NO-CC CODE,"Bronchiolitis obliterans organizing pneumonia (BOOP) is a chronic respiratory disease. Although the pathogenesis of BOOP is still incompletely understood, BOOP is responsive to steroids and has a good prognosis. In our five pigs with chronic postweaning multisystemic wasting syndrome (PMWS), typical BOOP lesions were revealed. All five porcine lungs showed typical intraluminal plugs, and porcine circovirus type 2 (PCV2) was identified. They also exhibited similar pathologic findings such as proliferation of type II pneumocytes and myofibroblasts (MFBs), extracellular collagen matrix (ECM) deposition, and fragmentation of elastic fibers. MFBs migration correlative molecules, for instance, gelatinase A, B and osteopontin, appeared strongly in the progressing marginal area of polypoid intraluminal plugs of fibrotic lesion. These molecules colocalized with the active MFBs. Both gelatinase activity and intercellular level of active MFBs were significantly increased (P < .05). Porcine chronic bronchopneumonia leads to BOOP and it is associated with PCV2 persistent infection. Swine BOOP demonstrates similar cellular constituents with human BOOP. Perhaps their molecular mechanisms of pathogenesis operate in a similar way. Thus we infer that the swine BOOP can be considered as a potential animal model for human BOOP associated with natural viral infection. Moreover, it is more convenient to obtain samples.",2011 Sep 27,"['Cheng, Ching-Chang', 'Lee, Yen-Feng', 'Lin, Nai-Nu', 'Wu, Chieh-Liang', 'Tung, Kwong-Chung', 'Chiu, Yung-Tsung']",J Biomed Biotechnol,,,True
1578499cbeda9a2abea8e444aab66575e8618b8c,PMC,"Capacity of Public Health Surveillance to Comply with Revised International Health Regulations, USA",http://dx.doi.org/10.3201/eid1605.091127,PMC2953987,20409370,NO-CC CODE,"Public health surveillance is essential for detecting and responding to infectious diseases and necessary for compliance with the revised International Health Regulations (IHR) 2005. To assess reporting capacities and compliance with IHR of all 50 states and Washington, DC, we sent a questionnaire to respective epidemiologists; 47 of 51 responded. Overall reporting capacity was high. Eighty-one percent of respondents reported being able to transmit notifications about unknown or unexpected events to the Centers for Disease Control and Prevention (CDC) daily. Additionally, 80% of respondents reported use of a risk assessment tool to determine whether CDC should be notified of possible public health emergencies. These findings suggest that most states have systems in place to ensure compliance with IHR. However, full state-level compliance will require additional efforts.",2010 May,"['Armstrong, Kia E.', 'McNabb, Scott J. N.', 'Ferland, Lisa D.', 'Stephens, Tim', 'Muldoon, Anna', 'Fernandez, Jose A.', 'Ostroff, Stephen']",Emerg Infect Dis,,,True
23f71cec67b168779d76b16f771126d98fc6f22e,PMC,Tropheryma whipplei in Children with Gastroenteritis,http://dx.doi.org/10.3201/eid1605.091801,PMC2954008,20409366,NO-CC CODE,"Tropheryma whipplei, which causes Whipple disease, is found in human feces and may cause gastroenteritis. To show that T. whipplei causes gastroenteritis, PCRs for T. whipplei were conducted with feces from children 2–4 years of age. Western blotting was performed for samples from children with diarrhea who had positive or negative results for T. whipplei. T. whipplei was found in samples from 36 (15%) of 241 children with gastroenteritis and associated with other diarrheal pathogens in 13 (33%) of 36. No positive specimen was detected for controls of the same age (0/47; p = 0.008). Bacterial loads in case-patients were as high as those in patients with Whipple disease and significantly higher than those in adult asymptomatic carriers (p = 0.002). High incidence in patients and evidence of clonal circulation suggests that some cases of gastroenteritis are caused or exacerbated by T. whipplei, which may be co-transmitted with other intestinal pathogens.",2010 May,"['Raoult, Didier', 'Fenollar, Florence', 'Rolain, Jean-Marc', 'Minodier, Philippe', 'Bosdure, Emmanuelle', 'Li, Wenjun', 'Garnier, Jean-Marc', 'Richet, Hervé']",Emerg Infect Dis,,,True
018460f6371890fe8cbb4cc74348cf6a9799b42d,PMC,Effects of Coronavirus Infections in Children,http://dx.doi.org/10.3201/eid1602.090469,PMC2957994,20113545,NO-CC CODE,"The isolation of the coronavirus (CoV) identified as the cause of severe acute respiratory syndrome and the detection of 2 new human CoVs (HCoV-NL63 and HCoV-HKU1) have led to studies of the epidemiology and clinical and socioeconomic effects of infections caused by all HCoVs, including those known since the late 1960s (HCoV-229E and HCoV-OC43). HCoV infections can be associated with respiratory and extrarespiratory manifestations, including central nervous system involvement. Furthermore, unlike other RNA viruses, HCoVs can easily mutate and recombine when different strains infect the same cells and give rise to a novel virus with unpredictable host ranges and pathogenicity. Thus, circulating HCoVs should be closely monitored to detect the spread of particularly virulent strains in the community at an early stage and to facilitate the development of adequate preventive and therapeutic measures.",2010 Feb,"['Principi, Nicola', 'Bosis, Samantha', 'Esposito, Susanna']",Emerg Infect Dis,,,False
79e0f0277142b321ccd75630f2405565e2ee64f3,PMC,Effects of Coronavirus Infections in Children,http://dx.doi.org/10.3201/eid1602.090469,PMC2957994,20113545,NO-CC CODE,"The isolation of the coronavirus (CoV) identified as the cause of severe acute respiratory syndrome and the detection of 2 new human CoVs (HCoV-NL63 and HCoV-HKU1) have led to studies of the epidemiology and clinical and socioeconomic effects of infections caused by all HCoVs, including those known since the late 1960s (HCoV-229E and HCoV-OC43). HCoV infections can be associated with respiratory and extrarespiratory manifestations, including central nervous system involvement. Furthermore, unlike other RNA viruses, HCoVs can easily mutate and recombine when different strains infect the same cells and give rise to a novel virus with unpredictable host ranges and pathogenicity. Thus, circulating HCoVs should be closely monitored to detect the spread of particularly virulent strains in the community at an early stage and to facilitate the development of adequate preventive and therapeutic measures.",2010 Feb,"['Principi, Nicola', 'Bosis, Samantha', 'Esposito, Susanna']",Emerg Infect Dis,,,True
e3eb479eab9c4630958978752dfdd3c5ce08d35a,PMC,Novel Human Bocavirus in Children with Acute Respiratory Tract Infection,http://dx.doi.org/10.3201/eid1602.090553,PMC2957997,20113572,NO-CC CODE,"Human bocavirus (HBoV) and HBoV2, two human bocavirus species, were found in 18 and 10 of 235 nasopharyngeal aspirates, respectively, from children hospitalized with acute respiratory tract infection. Our results suggest that, like HBoV, HBoV2 is distributed worldwide and may be associated with respiratory and enteric diseases.",2010 Feb,"['Song, Jing-rong', 'Jin, Yu', 'Xie, Zhi-ping', 'Gao, Han-chun', 'Xiao, Ni-guang', 'Chen, Wei-xia', 'Xu, Zi-qian', 'Yan, Kun-long', 'Zhao, Yang', 'Hou, Yun-de', 'Duan, Zhao-jun']",Emerg Infect Dis,,,True
9ffccb5731f62e6c18e8c6b4411204407cc4df1d,PMC,Employment and Compliance with Pandemic Influenza Mitigation Recommendations,http://dx.doi.org/10.3201/eid1602.090638,PMC2958001,20113549,NO-CC CODE,"In the event of a serious pandemic influenza outbreak, businesses must play a key role in protecting employees' health and safety. With regard to pandemic influenza mitigation recommendations requiring social distancing, we examined whether some US employees would disproportionately fail to comply because of job insecurity and financial problems associated with missing work. We used the 2006 Harvard School of Public Health Pandemic Influenza Survey and multivariable logistic regression to determine whether employment characteristics such as inability to work from home, lack of pay when absent from work, and self-employment would be associated with less ability to comply with recommendations. We found that inability to work from home, lack of paid sick leave, and income are associated with working adults’ ability to comply and should be major targets for workplace interventions in the event of a serious outbreak.",2010 Feb,"['Blake, Kelly D.', 'Blendon, Robert J.', 'Viswanath, Kasisomayajula']",Emerg Infect Dis,,,True
55503b79c71296ececcf4121f238db84d9e66d5a,PMC,"Hendra Virus Outbreak with Novel Clinical Features, Australia",http://dx.doi.org/10.3201/eid1602.090780,PMC2958006,20113576,NO-CC CODE,"To determine the epidemiologic and clinical features of a 2008 outbreak of Hendra virus infection in a veterinary clinic in Australia, we investigated the equine case-series. Four of 5 infected horses died, as did 1 of 2 infected staff members. Clinical manifestation in horses was predominantly neurologic. Preclinical transmission appears likely.",2010 Feb,"['Field, Hume', 'Schaaf, Kylie', 'Kung, Nina', 'Simon, Craig', 'Waltisbuhl, David', 'Hobert, Heather', 'Moore, Frederick', 'Middleton, Deborah', 'Crook, Allison', 'Smith, Greg', 'Daniels, Peter', 'Glanville, Ron', 'Lovell, David']",Emerg Infect Dis,,,False
a3ef5e2ffb31783af550c32f7512c0330ab9bc93,PMC,"Hendra Virus Outbreak with Novel Clinical Features, Australia",http://dx.doi.org/10.3201/eid1602.090780,PMC2958006,20113576,NO-CC CODE,"To determine the epidemiologic and clinical features of a 2008 outbreak of Hendra virus infection in a veterinary clinic in Australia, we investigated the equine case-series. Four of 5 infected horses died, as did 1 of 2 infected staff members. Clinical manifestation in horses was predominantly neurologic. Preclinical transmission appears likely.",2010 Feb,"['Field, Hume', 'Schaaf, Kylie', 'Kung, Nina', 'Simon, Craig', 'Waltisbuhl, David', 'Hobert, Heather', 'Moore, Frederick', 'Middleton, Deborah', 'Crook, Allison', 'Smith, Greg', 'Daniels, Peter', 'Glanville, Ron', 'Lovell, David']",Emerg Infect Dis,,,True
ee70b25804619797b5aeb8440a84203117ee36ef,PMC,A comparison of methods for purification and concentration of norovirus GII-4 capsid virus-like particles,http://dx.doi.org/10.1007/s00705-010-0768-z,PMC2970802,20721592,NO-CC CODE,"Noroviruses (NoVs) are one of the leading causes of acute gastroenteritis worldwide. NoV GII-4 VP1 protein was expressed in a recombinant baculovirus system using Sf9 insect cells. Several methods for purification and concentration of virus-like particles (VLPs) were evaluated. Electron microscopy (EM) and histo-blood group antigen (HBGA) binding assays showed that repeated sucrose gradient purification followed by ultrafiltration resulted in intact VLPs with excellent binding to H type 3 antigens. VLPs were stable for at least 12 months at 4°C, and up to 7 days at ambient temperature. These findings indicate that this method yielded stable and high-quality VLPs.",2010 Nov 19,"['Huhti, L.', 'Blazevic, V.', 'Nurminen, K.', 'Koho, T.', 'Hytönen, V. P.', 'Vesikari, T.']",Arch Virol,,,True
4b05e7b9898203b6bf0659c315eb9eb1f66f228c,PMC,Urine Peptidomic and Targeted Plasma Protein Analyses in the Diagnosis and Monitoring of Systemic Juvenile Idiopathic Arthritis,http://dx.doi.org/10.1007/s12014-010-9058-8,PMC2970804,21124648,NO-CC CODE,"PURPOSE: Systemic juvenile idiopathic arthritis is a chronic pediatric disease. The initial clinical presentation can mimic other pediatric inflammatory conditions, which often leads to significant delays in diagnosis and appropriate therapy. SJIA biomarker development is an unmet diagnostic/prognostic need to prevent disease complications. EXPERIMENTAL DESIGN: We profiled the urine peptidome to analyze a set of 102 urine samples, from patients with SJIA, Kawasaki disease (KD), febrile illnesses (FI), and healthy controls. A set of 91 plasma samples, from SJIA flare and quiescent patients, were profiled using a customized antibody array against 43 proteins known to be involved in inflammatory and protein catabolic processes. RESULTS: We identified a 17-urine-peptide biomarker panel that could effectively discriminate SJIA patients at active, quiescent, and remission disease states, and patients with active SJIA from confounding conditions including KD and FI. Targeted sequencing of these peptides revealed that they fall into several tight clusters from seven different proteins, suggesting disease-specific proteolytic activities. The antibody array plasma profiling identified an SJIA plasma flare signature consisting of tissue inhibitor of metalloproteinase-1 (TIMP1), interleukin (IL)-18, regulated upon activation, normal T cell expressed and secreted (RANTES), P-Selectin, MMP9, and L-Selectin. CONCLUSIONS AND CLINICAL RELEVANCE: The urine peptidomic and plasma protein analyses have the potential to improve SJIA care and suggest that SJIA urine peptide biomarkers may be an outcome of inflammation-driven effects on catabolic pathways operating at multiple sites. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12014-010-9058-8) contains supplementary material, which is available to authorized users.",2010 Dec 30,"['Ling, Xuefeng B.', 'Lau, Kenneth', 'Deshpande, Chetan', 'Park, Jane L.', 'Milojevic, Diana', 'Macaubas, Claudia', 'Xiao, Chris', 'Lopez-Avila, Viorica', 'Kanegaye, John', 'Burns, Jane C.', 'Cohen, Harvey', 'Schilling, James', 'Mellins, Elizabeth D.']",Clin Proteomics,,,True
06896d4cce2f5c7acef18238c110efec0865c2a7,PMC,"Henri Matisse (1869–1954). Icarus (from the illustrated book, Jazz, published in 1947 by E. Tériade)",http://dx.doi.org/10.3201/eid0905.AC0905,PMC2972775,,NO-CC CODE,,2003 May,"Potter, Polyxeni",Emerg Infect Dis,,,True
36102f647952cc83d82e800c7069bc2467214d2d,PMC,Severe Acute Respiratory Syndrome (SARS) in Singapore: Clinical Features of Index Patient and Initial Contacts,http://dx.doi.org/10.3201/eid0906.030264,PMC3000162,12781012,NO-CC CODE,"Severe acute respiratory syndrome (SARS) is an emerging viral infectious disease. One of the largest outbreaks of SARS to date began in Singapore in March 2003. We describe the clinical, laboratory, and radiologic features of the index patient and the patient’s initial contacts affected with probable SARS.",2003 Jun,"['Hsu, Li-Yang', 'Lee, Cheng-Chuan', 'Green, Justin A.', 'Ang, Brenda', 'Paton, Nicholas I.', 'Lee, Lawrence', 'Villacian, Jorge S.', 'Lim, Poh-Lian', 'Earnest, Arul', 'Leo, Yee-Sin']",Emerg Infect Dis,,,True
704f0c7ab057483ee618adfe0926eacab4227187,PMC,Control Measures for Severe Acute Respiratory Syndrome (SARS) in Taiwan,http://dx.doi.org/10.3201/eid0906.030283,PMC3000163,12781013,NO-CC CODE,"As of April 14, 2003, Taiwan had had 23 probable cases of severe acute respiratory syndrome (SARS), all imported. Taiwan isolated these first 23 patients with probable SARS in negative-pressure rooms; extensive personal protective equipment was used for healthcare workers and visitors. For the first 6 weeks of the SARS outbreak, recognized spread was limited to one healthcare worker and three household contacts.",2003 Jun,"['Twu, Shiing-Jer', 'Chen, Tzay-Jinn', 'Chen, Chien-Jen', 'Olsen, Sonja J.', 'Lee, Long-Teng', 'Fisk, Tamara', 'Hsu, Kwo-Hsiung', 'Chang, Shan-Chwen', 'Chen, Kow-Tong', 'Chiang, I-Hsin', 'Wu, Yi-Chun', 'Wu, Jiunn-Shyan', 'Dowell, Scott F.']",Emerg Infect Dis,,,True
b19a21295cdc5bb0be8ddc6688268147a0a6d510,PMC,Transmission of communicable respiratory infections and facemasks,,PMC3004550,21197329,NO-CC CODE,"BACKGROUND: Respiratory protection efficiency of facemasks is critically important in the battle against communicable respiratory infections such as influenza and severe acute respiratory syndrome (SARS). We studied the spatial distributions of simulated virus-laden respiratory droplets when human subjects wore facemasks and were exposed to regulatory viral droplets by conducting in vivo experiments in facemask use. METHODS: Transmission pathway of aerosols of Fluorescein-KCl solution through facemasks and protective efficiency of facemasks were examined by using normal surgical facemasks and two facemasks with exhaust valves (Facemask A) and exhaust holes (Facemask B) covered with the same surgical filters situated at the back of the facemasks. Fluorescein-KCl solution was sprayed onto the faces of participants wearing the facemasks and performing intermittent exercises on a treadmill in a climatic chamber. RESULTS: Experimental results showed that when droplets spread onto a person face-to-face over short distances, 92.3% to 99.5% of droplets were blocked by the front surface of the facemask, whereas only 0.5% to 7.7% of droplets reached the back of the facemask. Both facemasks A and B had near or over 99% protection efficiency, compared with that of 95.5% to 97% of surgical facemasks. Using the same filters as normal surgical masks, facemasks A and B provided more effective respiratory protection against communicable respiratory infections such as influenza and SARS by the location of the breathing pathway to the back of the facemasks. CONCLUSIONS: Separating the breathing pathway from the virus-contaminated area in facemasks can provide more effective protection against communicable respiratory infections such as influenza and SARS.",2008 May 1,"['Li, Yi', 'Guo, Yue Ping', 'Wong, Kwok Ching Thomas', 'Chung, Wai Yee Joanne', 'Gohel, Mayur Danny Indulal', 'Leung, Hang Mei Polly']",J Multidiscip Healthc,,,True
b59de45467bf403971b02fc44bc84f4e75bfbdfa,PMC,Two resource distribution strategies for dynamic mitigation of influenza pandemics,,PMC3004603,21197356,NO-CC CODE,"As recently pointed out by the Institute of Medicine, the existing pandemic containment and mitigation models lack the dynamic decision support capabilities. We present two simulation-based optimization models for developing dynamic predictive resource distribution strategies for cross-regional pandemic outbreaks. In both models, the underlying simulation mimics the disease and population dynamics of the affected regions. The quantity-based optimization model generates a progressive allocation of limited quantities of mitigation resources, including vaccines, antiviral, administration capacities, and social distancing enforcement resources. The budget-based optimization model strives instead allocating a total resource budget. Both models seek to minimize the impact of ongoing outbreaks and the expected impact of potential outbreaks. The models incorporate measures of morbidity, mortality, and social distancing, translated into the societal and economic costs of lost productivity and medical expenses. The models were calibrated using historic pandemic data and implemented on a sample outbreak in Florida, with over four million inhabitants. The quantity-based model was found to be inferior to the budget-based model, which was advantageous in its ability to balance the varying relative cost and effectiveness of individual resources. The models are intended to assist public health policy makers in developing effective distribution policies for mitigation of influenza pandemics.",2010 Jul 7,"['Uribe-Sánchez, Andrés', 'Savachkin, Alex']",J Multidiscip Healthc,,,True
6c0dee643345c93436cfa8d58270aa887ad92e3d,PMC,The Virus That Changed My World,http://dx.doi.org/10.1371/journal.pbio.0000066,PMC300679,14691538,NO-CC CODE,Personal account of a young virologist working in Singapore at the height of the 2003 SARS pandemic,2003 Dec 22,"Poh Ng, Lisa Fong",PLoS Biol,,,True
f4dd6a079963031a5fc8012b659c9bff14e739a6,PMC,Lectins: production and practical applications,http://dx.doi.org/10.1007/s00253-010-2892-9,PMC3016214,20890754,NO-CC CODE,"Lectins are proteins found in a diversity of organisms. They possess the ability to agglutinate erythrocytes with known carbohydrate specificity since they have at least one non-catalytic domain that binds reversibly to specific monosaccharides or oligosaccharides. This articles aims to review the production and practical applications of lectins. Lectins are isolated from their natural sources by chromatographic procedures or produced by recombinant DNA technology. The yields of animal lectins are usually low compared with the yields of plant lectins such as legume lectins. Lectins manifest a diversity of activities including antitumor, immunomodulatory, antifungal, HIV-1 reverse transcriptase inhibitory, and anti-insect activities, which may find practical applications. A small number of lectins demonstrate antibacterial and anti-nematode activities.",2011 Jan 3,"['Lam, Sze Kwan', 'Ng, Tzi Bun']",Appl Microbiol Biotechnol,,,True
951bc7b3cf514d9077b2cd520cad9e6089f0e558,PMC,Mild Severe Acute Respiratory Syndrome,http://dx.doi.org/10.3201/eid0909.030461,PMC3016760,14531381,NO-CC CODE,,2003 Sep,"['Li, Gang', 'Zhao, Zhixin', 'Chen, Lubiao', 'Zhou, Yihua']",Emerg Infect Dis,,,True
9d3a3e66c47a288c1ae7048c853a583c4eabf721,PMC,Role of China in the Quest to Define and Control Severe Acute Respiratory Syndrome,http://dx.doi.org/10.3201/eid0909.030390,PMC3016762,14519236,NO-CC CODE,"China holds the key to solving many questions crucial to global control of severe acute respiratory syndrome (SARS). The disease appears to have originated in Guangdong Province, and the causative agent, SARS coronavirus, is likely to have originated from an animal host, perhaps sold in public markets. Epidemiologic findings, integral to defining an animal-human linkage, may then be confirmed by laboratory studies; once animal host(s) are confirmed, interventions may be needed to prevent further animal-to-human transmission. Community seroprevalence studies may help determine the basis for the decline in disease incidence in Guangdong Province after February 2002. China will also be able to contribute key data about how the causative agent is transmitted and how it is evolving, as well as identifying pivotal factors influencing disease outcome. There must be support for systematically addressing these fundamental questions in China and rapidly disseminating results.",2003 Sep,"['Breiman, Robert F.', 'Evans, Meirion R.', 'Preiser, Wolfgang', 'Maguire, James', 'Schnur, Alan', 'Bekedam, Henk', 'MacKenzie, John S.']",Emerg Infect Dis,,,True
601183372b370d59a83b1d68598cb594f9397777,PMC,Transmission of Severe Acute Respiratory Syndrome,http://dx.doi.org/10.3201/eid0909.030471,PMC3016764,14531382,NO-CC CODE,,2003 Sep,"['Arita, Isao', 'Kojima, Kazunobu', 'Nakane, Miyuki']",Emerg Infect Dis,,,True
9d26cdd19afaaa9f93ff6b4a6741f4fb3eb33e4e,PMC,Lessons from the Severe Acute Respiratory Syndrome Outbreak in Hong Kong,http://dx.doi.org/10.3201/eid0909.030366,PMC3016765,14519237,NO-CC CODE,"Severe acute respiratory syndrome (SARS) is now a global public health threat with many medical, ethical, social, economic, political, and legal implications. The nonspecific signs and symptoms of this disease, coupled with a relatively long incubation period and the initial absence of a reliable diagnostic test, limited the understanding of the magnitude of the outbreak. This paper outlines our experience with public health issues that have arisen during this outbreak of SARS in Hong Kong. We confirmed that case detection, reporting, clear and timely dissemination of information, and strict infection control measures are essential in handling such an infectious disease outbreak. The need for an outbreak response unit is crucial to combat any future outbreak.",2003 Sep,"['Abdullah, Abu S.M.', 'Tomlinson, Brian', 'Cockram, Clive S.', 'Thomas, G. Neil']",Emerg Infect Dis,,,True
050b683c5336bc0243b53caed1df50fbf52e0727,PMC,World Health Organization Global Conference on Severe Acute Respiratory Syndrome,http://dx.doi.org/10.3201/eid0909.030559,PMC3016766,14531385,NO-CC CODE,,2003 Sep,"['Bell, David', 'Jenkins, Philip', 'Hall, Julie']",Emerg Infect Dis,,,False
608f11c80d206e1ca59ef5683a1b31d689c79102,PMC,About the Cover Vincent van Gogh (1853–1890). The Prison Courtyard (1890),http://dx.doi.org/10.3201/eid0909.AC0909,PMC3016769,14531386,NO-CC CODE,,2003 Sep,"Potter, Polyxeni",Emerg Infect Dis,,,True
2a10dd7be4d35acd837cdec5d058541d13def6c3,PMC,"Microbiologic Characteristics, Serologic Responses, and Clinical Manifestations in Severe Acute Respiratory Syndrome, Taiwan",http://dx.doi.org/10.3201/eid0909.030367,PMC3016775,14519257,NO-CC CODE,"The genome of one Taiwanese severe acute respiratory syndrome-associated coronavirus (SARS-CoV) strain (TW1) was 29,729 nt in length. Viral RNA may persist for some time in patients who seroconvert, and some patients may lack an antibody response (immunoglobulin G) to SARS-CoV >21 days after illness onset. An upsurge of antibody response was associated with the aggravation of respiratory failure.",2003 Sep,"['Hsueh, Po-Ren', 'Hsiao, Cheng-Hsiang', 'Yeh, Shiou-Hwei', 'Wang, Wei-Kung', 'Chen, Pei-Jer', 'Wang, Jin-Town', 'Chang, Shan-Chwen', 'Kao, Chuan-Liang', 'Yang, Pan-Chyr', None]",Emerg Infect Dis,,,True
88534ac83f589e5b7cfcb52ac0062db7b6b101ac,PMC,Human Metapneumovirus Detection in Patients with Severe Acute Respiratory Syndrome,http://dx.doi.org/10.3201/eid0909.030304,PMC3016779,14519240,NO-CC CODE,"We used a combination approach of conventional virus isolation and molecular techniques to detect human metapneumovirus (HMPV) in patients with severe acute respiratory syndrome (SARS). Of the 48 study patients, 25 (52.1%) were infected with HMPV; 6 of these 25 patients were also infected with coronavirus, and another 5 patients (10.4%) were infected with coronavirus alone. Using this combination approach, we found that human laryngeal carcinoma (HEp-2) cells were superior to rhesus monkey kidney (LLC-MK2) cells commonly used in previous studies for isolation of HMPV. These widely available HEp-2 cells should be included in conjunction with a molecular method for cell culture followup to detect HMPV, particularly in patients with SARS.",2003 Sep,"['Chan, Paul K.S.', 'Tam, John S.', 'Lam, Ching-Wan', 'Chan, Edward', 'Wu, Alan', 'Li, Chi-Kong', 'Buckley, Thomas A.', 'Ng, King-Cheung', 'Joynt, Gavin M.', 'Cheng, Frankie W.T.', 'To, Ka-Fai', 'Lee, Nelson', 'Hui, David S.C.', 'Cheung, Jo L.K.', 'Chu, Ida', 'Liu, Esther', 'Chung, Sydney S.C.', 'Sung, Joseph J.Y.']",Emerg Infect Dis,,,True
3f893c8176209b798e129adac6c6ce6b17631a27,PMC,Severe Acute Respiratory Syndrome: Relapse? Hospital Infection?,http://dx.doi.org/10.3201/eid0909.030395,PMC3016786,14531379,NO-CC CODE,,2003 Sep,"['Tsang, Owen Tak-Yin', 'Chau, Tai-Nin', 'Choi, Kin-Wing', 'Tso, Eugene Yuk-Keung', 'Lim, Wilina', 'Chiu, Ming-Chi', 'Tong, Wing-Lok', 'Lee, Po-Oi', 'Lam, Bosco Hoi Shiu', 'Ng, Tak-Keung', 'Lai, Jak-Yiu', 'Yu, Wai-Cho', 'Lai, Sik-To']",Emerg Infect Dis,,,True
595556e68d7c883581515ebc68d1ca3aa786e44d,PMC,The Global Threat of New and Reemerging Infectious Diseases: Reconciling U.S. National Security and Public Health Policy,http://dx.doi.org/10.3201/eid0909.030442,PMC3016794,,NO-CC CODE,,2003 Sep,"McConnon, Patrick J.",Emerg Infect Dis,,,False
361e12416e0ff49f28521c2dc5fc69934e419910,PMC,Severe Acute Respiratory Syndrome: Clinical Outcome and Prognostic Correlates,http://dx.doi.org/10.3201/eid0909.030362,PMC3016795,14519241,NO-CC CODE,"Severe acute respiratory syndrome (SARS) poses a major threat to the health of people worldwide. We performed a retrospective case series analysis to assess clinical outcome and identify pretreatment prognostic correlates of SARS, managed under a standardized treatment protocol. We studied 127 male and 196 female patients with a mean age of 41±14 (range 18–83). All patients, except two, received ribavirin and steroid combination therapy. In 115 (36%) patients, the course of disease was limited. Pneumonitis progressed rapidly in the remaining patients. Sixty-seven (21%) patients required intensive care, and 42 (13%) required ventilator support. Advanced age, high admission neutrophil count, and high initial lactate dehydrogenase level were independent correlates of an adverse clinical outcome. SARS-associated coronavirus caused severe illnesses in most patients, despite early treatment with ribavirin and steroid. This study has identified three independent pretreatment prognostic correlates.",2003 Sep,"['Tsui, Ping Tim', 'Kwok, Man Leung', 'Yuen, Hon', 'Lai, Sik To']",Emerg Infect Dis,,,True
73ff82d21abeaf54a23fddf5354da59c0890a95a,PMC,Severe Acute Respiratory Syndrome: Temporal Stability and Geographic Variation in Death Rates and Doubling Times,http://dx.doi.org/10.3201/eid0908.030334,PMC3020622,12967499,NO-CC CODE,"We analyzed temporal stability and geographic trends in cumulative case-fatality rates and average doubling times of severe acute respiratory syndrome (SARS). In part, we account for correlations between case-fatality rates and doubling times through differences in control measures. Factors that may alter future estimates of case-fatality rates, reasons for heterogeneity in doubling times among countries, and implications for the control of SARS are discussed.",2003 Aug,"['Galvani, Alison P.', 'Lei, Xiudong', 'Jewell, Nicholas P.']",Emerg Infect Dis,,,False
7b9fb5e842666cdb5418bacb81aefb0226088c06,PMC,Severe Acute Respiratory Syndrome: Temporal Stability and Geographic Variation in Death Rates and Doubling Times,http://dx.doi.org/10.3201/eid0908.030334,PMC3020622,12967499,NO-CC CODE,"We analyzed temporal stability and geographic trends in cumulative case-fatality rates and average doubling times of severe acute respiratory syndrome (SARS). In part, we account for correlations between case-fatality rates and doubling times through differences in control measures. Factors that may alter future estimates of case-fatality rates, reasons for heterogeneity in doubling times among countries, and implications for the control of SARS are discussed.",2003 Aug,"['Galvani, Alison P.', 'Lei, Xiudong', 'Jewell, Nicholas P.']",Emerg Infect Dis,,,True
db40a1dfdecdf2427c6d0a22c0affdbeda3cb25a,PMC,Jan Steen (c. 1625–1679). Beware of Luxury (c. 1665).,http://dx.doi.org/10.3201/eid0908.AC0908,PMC3020624,,NO-CC CODE,,2003 Aug,"Potter, Polyxeni",Emerg Infect Dis,,,True
d09b79026117ec9faebba46a8d13aa9b23ec751e,PMC,A Method to Identify p62's UBA Domain Interacting  Proteins,http://dx.doi.org/10.1251/bpo66,PMC302190,14702098,NO-CC CODE,"The UBA domain is a conserved sequence motif among polyubiquitin binding proteins. For the first time, we demonstrate a systematic, high throughput approach to identification of UBA domain-interacting proteins from a proteome-wide perspective. Using the rabbit reticulocyte lysate in vitro expression cloning system, we have successfully identified eleven proteins that interact with p62’s UBA domain, and the majority of the eleven proteins are associated with neurodegenerative disorders, such as Alzheimer’s disease. Therefore, p62 may play a novel regulatory role through its UBA domain. Our approach provides an easy route to the characterization of UBA domain interacting proteins and its application will unfold the important roles that the UBA domain plays.",2003 Dec 12,"['Pridgeon, Julia W.', 'Geetha, Thangiah', 'Wooten, Marie W.']",Biol Proced Online,,,True
dd798f4e35268f8ab935a299973627fc3082864a,PMC,Swabbing for respiratory viral infections in older patients: a comparison of rayon and nylon flocked swabs,http://dx.doi.org/10.1007/s10096-010-1064-2,PMC3022161,20853014,NO-CC CODE,"The purpose of this study was to compare the sampling efficacy of rayon swabs and nylon flocked swabs, and of oropharyngeal and nasopharyngeal specimens for the detection of respiratory viruses in elderly patients. Samples were obtained from patients 60 years of age or above who were newly admitted to Sorlandet Hospital Arendal, Norway. The patients were interviewed for current symptoms of a respiratory tract infection. Using rayon swabs and nylon flocked swabs, comparable sets of mucosal samples were harvested from the nasopharynx and the oropharynx. The samples were analysed using real-time polymerase chain reaction (PCR) methods. A total of 223 patients (mean age 74.9 years, standard deviation [SD] 9.0 years) were swabbed and a virus was recovered from 11% of the symptomatic patients. Regardless of the sampling site, a calculated 4.8 times higher viral load (95% confidence interval [CI] 1.3–17, p = 0.017) was obtained using the nylon flocked swabs as compared to the rayon swabs. Also, regardless of the type of swab, a calculated 19 times higher viral load was found in the samples from the nasopharynx as compared to the oropharynx (95% CI 5.4–67.4, p < 0.001). When swabbing for respiratory viruses in elderly patients, nasopharyngeal rather than oropharyngeal samples should be obtained. Nylon flocked swabs appear to be more efficient than rayon swabs.",2011 Feb 18,"['Hernes, S. S.', 'Quarsten, H.', 'Hagen, E.', 'Lyngroth, A. L.', 'Pripp, A. H.', 'Bjorvatn, B.', 'Bakke, P. S.']",Eur J Clin Microbiol Infect Dis,,,True
16715be315ab1392947070e15252a60ae2b745f8,PMC,Current progress in the development of a prophylactic vaccine for HIV-1,http://dx.doi.org/10.2147/DDDT.S6959,PMC3023272,21267356,NO-CC CODE,"Since its discovery and characterization in the early 1980s as a virus that attacks the immune system, there has been some success for the treatment of human immunodeficiency virus-1 (HIV-1) infection. However, due to the overwhelming public health impact of this virus, a vaccine is needed urgently. Despite the tireless efforts of scientist and clinicians, there is still no safe and effective vaccine that provides sterilizing immunity. A vaccine that provides sterilizing immunity against HIV infection remains elusive in part due to the following reasons: 1) degree of diversity of the virus, 2) ability of the virus to evade the hosts’ immunity, and 3) lack of appropriate animal models in which to test vaccine candidates. There have been several attempts to stimulate the immune system to provide protection against HIV-infection. Here, we will discuss attempts that have been made to induce sterilizing immunity, including traditional vaccination attempts, induction of broadly neutralizing antibody production, DNA vaccines, and use of viral vectors. Some of these attempts show promise pending continued research efforts.",2010 Dec 22,"['Gamble, Lena J', 'Matthews, Qiana L']",Drug Des Devel Ther,,,True
59ed1130893561378ca9da3fe95361433673ca9d,PMC,"Jacques-Louis David (1748–1825). Coronation of Empress Josephine by Napoleon I at Notre Dame de Paris, 2 December 1804 (1806–1807)",http://dx.doi.org/10.3201/eid0910.AC0910,PMC3033066,,NO-CC CODE,,2003 Oct,"Potter, Polyxeni",Emerg Infect Dis,,,False
d46d2f01a570bfb6e3b2e65ec50972d1649b6a3d,PMC,Severe Acute Respiratory Syndrome: Lessons from Singapore,http://dx.doi.org/10.3201/eid0910.030388,PMC3033073,14609466,NO-CC CODE,"An outbreak of severe acute respiratory syndrome (SARS) occurred in Singapore in March 2003. To illustrate the problems in diagnosing and containing SARS in the hospital, we describe a case series and highlight changes in triage and infection control practices that resulted. By implementing these changes, we have stopped the nosocomial transmission of the virus.",2003 Oct,"['Singh, Kamaljit', 'Hsu, Li-Yang', 'Villacian, Jorge S.', 'Habib, Abdulrazaq', 'Fisher, Dale', 'Tambyah, Paul A.']",Emerg Infect Dis,,,True
64b175f9110dce9c9995d872ba7f7b3671e52f5b,PMC,Illness in Intensive Care Staff after Brief Exposure to Severe Acute Respiratory Syndrome,http://dx.doi.org/10.3201/eid0910.030525,PMC3033076,14609453,NO-CC CODE,,2003 Oct,"['Scales, Damon C.', 'Green, Karen', 'Chan, Adrienne K.', 'Poutanen, Susan M.', 'Foster, Donna', 'Nowak, Kylie', 'Raboud, Janet M.', 'Saskin, Refik', 'Lapinsky, Stephen E.', 'Stewart, Thomas E.']",Emerg Infect Dis,,,True
b4ac66a59b0e40c10a447b7a90f5c03d03eb58dc,PMC,The European Commission’s Task Force on Bioterrorism,http://dx.doi.org/10.3201/eid0910.030368,PMC3033083,14609475,NO-CC CODE,"In response to the increased threat of bioterrorism, a task force on health security was established in the European Commission. Task force members address a broad range of issues related to preparedness for and response to bioterrorist events and seek to bring about a greater collaboration between the European Union member states.",2003 Oct,"['Tegnell, Anders', 'Bossi, Philippe', 'Baka, Agoritsa', 'Van Loock, Frank', 'Hendriks, Jan', 'Wallyn, Solvejg', 'Gouvras, Georgios']",Emerg Infect Dis,,,True
ddb2b05c81507bb243a857b3bdc61bb9b24b4686,PMC,Severe Acute Respiratory Syndrome Epidemic in Asia,http://dx.doi.org/10.3201/eid0912.030382,PMC3034341,14720403,NO-CC CODE,"We analyzed the dynamics of cumulative severe acute respiratory syndrome (SARS) cases in Singapore, Hong Kong, and Beijing using the Richards model. The predicted total SARS incidence was close to the actual number of cases; the predicted cessation date was close to the lower limit of the 95% confidence interval.",2003 Dec,"['Zhou, Guofa', 'Yan, Guiyun']",Emerg Infect Dis,,,False
54ce6d742da5a2312aeea36c4d92f5fc0208538c,PMC,Severe Acute Respiratory Syndrome Epidemic in Asia,http://dx.doi.org/10.3201/eid0912.030382,PMC3034341,14720403,NO-CC CODE,"We analyzed the dynamics of cumulative severe acute respiratory syndrome (SARS) cases in Singapore, Hong Kong, and Beijing using the Richards model. The predicted total SARS incidence was close to the actual number of cases; the predicted cessation date was close to the lower limit of the 95% confidence interval.",2003 Dec,"['Zhou, Guofa', 'Yan, Guiyun']",Emerg Infect Dis,,,True
8e49f1654890f932661f31d95f1d8353221c5eee,PMC,Severe Acute Respiratory Syndrome Epidemic in Asia,http://dx.doi.org/10.3201/eid0912.030382,PMC3034341,14720403,NO-CC CODE,"We analyzed the dynamics of cumulative severe acute respiratory syndrome (SARS) cases in Singapore, Hong Kong, and Beijing using the Richards model. The predicted total SARS incidence was close to the actual number of cases; the predicted cessation date was close to the lower limit of the 95% confidence interval.",2003 Dec,"['Zhou, Guofa', 'Yan, Guiyun']",Emerg Infect Dis,,,False
2dd04a587ffcdb375a958d05f133c707ab782454,PMC,Atlas of Travel Medicine and Health,http://dx.doi.org/10.3201/eid0911.030503,PMC3035546,,NO-CC CODE,,2003 Nov,"Chen, Lin H.",Emerg Infect Dis,,,False
7c754c95f6614150c41ea4c07cfe7e781f3a165d,PMC,Coronavirus-positive Nasopharyngeal Aspirate as Predictor for Severe Acute Respiratory Syndrome Mortality,http://dx.doi.org/10.3201/eid0911.030400,PMC3035547,14718079,NO-CC CODE,"Severe acute respiratory syndrome (SARS) has caused a major epidemic worldwide. A novel coronavirus is deemed to be the causative agent. Early diagnosis can be made with reverse transcriptase-polymerase chain reaction (RT-PCR) of nasopharyngeal aspirate samples. We compared symptoms of 156 SARS-positive and 62 SARS-negative patients in Hong Kong; SARS was confirmed by RT-PCR. The RT-PCR–positive patients had significantly more shortness of breath, a lower lymphocyte count, and a lower lactate dehydrogenase level; they were also more likely to have bilateral and multifocal chest radiograph involvement, to be admitted to intensive care, to need mechanical ventilation, and to have higher mortality rates. By multivariate analysis, positive RT-PCR on nasopharyngeal aspirate samples was an independent predictor of death within 30 days.",2003 Nov,"['Tsang, Owen Tak-Yin', 'Chau, Tai-Nin', 'Choi, Kin-Wing', 'Tso, Eugene Yuk-Keung', 'Lim, Wilina', 'Chiu, Ming-Chi', 'Tong, Wing-Lok', 'Lee, Po-Oi', 'Lam, Bosco Hoi Shiu', 'Ng, Tak-Keung', 'Lai, Jak-Yiu', 'Yu, Wai-Cho', 'Lai, Sik-To']",Emerg Infect Dis,,,True
00573277e6be50669016f770bc28ec2da0639a8f,PMC,Asymptomatic Severe Acute Respiratory Syndrome–associated Coronavirus Infection,http://dx.doi.org/10.3201/eid0911.030401,PMC3035549,14725258,NO-CC CODE,,2003 Nov,"['Lee, Harold K.K.', 'Tso, Eugene Y.K.', 'Chau, T. N.', 'Tsang, Owen T.Y.', None, 'Choi, W.', 'Lai, Thomas S.T.']",Emerg Infect Dis,,,True
ae5583765a6a5c11926b7d4b3820d4ee98defe64,PMC,Flow Cytometry and T-Cell Response Monitoring after Smallpox Vaccination,http://dx.doi.org/10.3201/eid0911.030349,PMC3035552,14718095,NO-CC CODE,"Orthopoxvirus zoonosis or smallpox as result of bioterrorism or biological warfare represents a risk for epidemic spread. By monitoring T-cell responses by flow cytometry, we observed a recall response after recent vaccination against smallpox. When the high similarity between the orthopoxviruses is considered, this rapid assay that uses vaccinia antigens could identify recently exposures.",2003 Nov,"['Poccia, Fabrizio', 'Gioia, Cristiana', 'Montesano, Carla', 'Martini, Federico', 'Horejsh, Douglas', 'Castilletti, Concetta', 'Pucillo, Leopoldo Paolo', 'Capobianchi, Maria Rosaria', 'Ippolito, Giuseppe']",Emerg Infect Dis,,,True
38731c8391dd2178df3d10c3db375d000428407d,PMC,Severe Acute Respiratory Syndrome–associated Coronavirus Infection,http://dx.doi.org/10.3201/eid0911.030421,PMC3035556,14718090,NO-CC CODE,"Whether severe acute respiratory syndrome–associated coronavirus (SARS-CoV) infection can be asymptomatic is unclear. We examined the seroprevalence of SARS-CoV among 674 healthcare workers from a hospital in which a SARS outbreak had occurred. A total of 353 (52%) experienced mild self-limiting illnesses, and 321 (48%) were asymptomatic throughout the course of these observations. None of these healthcare workers had antibody to SARS CoV, indicating that subclinical or mild infection attributable to SARS CoV in adults is rare.",2003 Nov,"['Chan, Paul K.S.', 'Ip, Margaret', 'Ng, KC', 'Chan, Rickjason C. W.', 'Wu, Alan', 'Lee, Nelson', 'Rainer, Timothy H.', 'Joynt, Gavin M.', 'Sung, Joseph J. Y.', 'Tam, John S.']",Emerg Infect Dis,,,True
f2cc8e8c4fa06d2af961fe2c2bab8c2d1e2849b3,PMC,Mechanisms of viral entry: sneaking in the front door,http://dx.doi.org/10.1007/s00709-010-0152-6,PMC3038234,20446005,NO-CC CODE,"Recent developments in methods to study virus internalisation are providing clearer insights into mechanisms used by viruses to enter host cells. The use of dominant negative constructs, specific inhibitory drugs and RNAi to selectively prevent entry through particular pathways has provided evidence for the clathrin-mediated entry of hepatitis C virus (HCV) as well as the caveolar entry of Simian Virus 40. Moreover, the ability to image and track fluorescent-labelled virus particles in real-time has begun to challenge the classical plasma membrane entry mechanisms described for poliovirus and human immunodeficiency virus. This review will cover both well-documented entry mechanisms as well as more recent discoveries in the entry pathways of enveloped and non-enveloped viruses. This will include viruses which enter the cytosol directly at the plasma membrane and those which enter via endocytosis and traversal of internal membrane barrier(s). Recent developments in imaging and inhibition of entry pathways have provided insights into the ill-defined entry mechanism of HCV, bringing it to the forefront of viral entry research. Finally, as high-affinity receptors often define viral internalisation pathways, and tropism in vivo, host membrane proteins to which viral particles specifically bind will be discussed throughout.",2010 Aug 6,"['Thorley, Jennifer A.', 'McKeating, Jane A.', 'Rappoport, Joshua Zachary']",Protoplasma,,,True
58bb4af3c8facbfe1aa740dc5893a5b4518807f7,PMC,"New Adenovirus in Bats, Germany",http://dx.doi.org/10.3201/eid1512.090646,PMC3044533,19961700,NO-CC CODE,"We tested 55 deceased vespertilionid bats of 12 species from southern Germany for virus infections. A new adenovirus was isolated from tissue samples of 2 Pipistrellus pipistrellus bats, which represents the only chiropteran virus isolate found in Europe besides lyssavirus (rabies virus). Evidence was found for adenovirus transmission between bats.",2009 Dec,"['Sonntag, Michael', 'Mühldorfer, Kristin', 'Speck, Stephanie', 'Wibbelt, Gudrun', 'Kurth, Andreas']",Emerg Infect Dis,,,True
6204ddfab367830e9fb70d356967ee25b13ab546,PMC,Cost-effectiveness Analysis of Hospital Infection Control Response to an Epidemic Respiratory Virus Threat,http://dx.doi.org/10.3201/eid1512.090902,PMC3044543,19961669,NO-CC CODE,"The outbreak of influenza A pandemic (H1N1) 2009 prompted many countries in Asia, previously strongly affected by severe acute respiratory syndrome (SARS), to respond with stringent measures, particularly in preventing outbreaks in hospitals. We studied actual direct costs and cost-effectiveness of different response measures from a hospital perspective in tertiary hospitals in Singapore by simulating outbreaks of SARS, pandemic (H1N1) 2009, and 1918 Spanish influenza. Protection measures targeting only infected patients yielded lowest incremental cost/death averted of $23,000 (US$) for pandemic (H1N1) 2009. Enforced protection in high-risk areas (Yellow Alert) and full protection throughout the hospital (Orange Alert) averted deaths but came at an incremental cost of up to $2.5 million/death averted. SARS and Spanish influenza favored more stringent measures. High case-fatality rates, virulence, and high proportion of atypical manifestations impacted cost-effectiveness the most. A calibrated approach in accordance with viral characteristics and community risks may help refine responses to future epidemics.",2009 Dec,"['Dan, Yock Young', 'Tambyah, Paul A.', 'Sim, Joe', 'Lim, Jeremy', 'Hsu, Li Yang', 'Chow, Wai Leng', 'Fisher, Dale A.', 'Wong, Yue Sie', 'Ho, Khek Yu']",Emerg Infect Dis,,,True
664563d8f7858aa1fe412414d4728b9243930e5a,PMC,"Respiratory Infection in Institutions during Early Stages of Pandemic (H1N1) 2009, Canada",http://dx.doi.org/10.3201/eid1512.091022,PMC3044548,19961686,NO-CC CODE,"Outbreaks of respiratory infection in institutions in Ontario, Canada were studied from April 20 to June 12, 2009, during the early stages of the emergence of influenza A pandemic (H1N1) 2009. Despite widespread presence of influenza in the general population, only 2 of 83 outbreaks evaluated by molecular methods were associated with pandemic (H1N1) 2009.",2009 Dec,"['Marchand-Austin, Alex', 'Farrell, David J.', 'Jamieson, Frances B.', 'Lombardi, Nino', 'Lombos, Ernesto', 'Narang, Sunita', 'Akwar, Holy', 'Low, Donald E.', 'Gubbay, Jonathan B.']",Emerg Infect Dis,,,True
e88710cd7b238794bd75f21d308bc5442ad9713f,PMC,Efficacy and safety of a multiherbal formula with vitamin C and zinc (Immumax) in the management of the common cold,http://dx.doi.org/10.2147/IJGM.S16266,PMC3048339,21403792,NO-CC CODE,"OBJECTIVE: To study the potential efficacy and tolerability of a natural multiherbal formula (Immumax) containing Echinacea extract 120 mg, garlic powder 100 mg, Nigella sativa oil 200 mg, and Panax ginseng extract 50 mg plus vitamin C 50 mg and elemental zinc 7.5 mg in the treatment of patients suffering from the common cold. DESIGN AND SETTING: The study was conducted in a prospective, double-blind, randomized, controlled study design in an outpatient setting. PATIENTS AND METHODS: Sixty-two eligible patients with symptoms of the common cold were randomized to either Immumax or placebo treatment groups for the duration of their symptoms or a maximum of 14 days. Resolution rates were estimated using Kaplan–Meier analysis, and resolution profiles were compared between groups using the log-rank test. The mean percentage change in total symptom severity scores at days 4 and 8 from baseline were compared between the two groups by one-way analysis of variance (ANOVA). RESULTS: The median (interquartile range) time to resolution of all symptoms was 8 (5–9) days in the placebo group and 4 (3–6) days in the Immumax group. The results of the log-rank test indicate that symptoms resolved significantly faster in the Immumax group than in the placebo group (P < 0.001). The mean percentage reduction in total symptom severity scores from baseline at days 4 and 8 was significantly greater in the Immumax group than in the placebo group by one-way ANOVA (P < 0.01). CONCLUSION: We can conclude from our study that Immumax is helpful in reducing the duration and severity of common cold symptoms.",2011 Jan 12,"['Yakoot, Mostafa', 'Salem, Amel']",Int J Gen Med,,,True
8b922efc32e8afde38542d35e9941e86c07ca6a0,PMC,Role of glutathione in immunity and inflammation in the lung,http://dx.doi.org/10.2147/IJGM.S15618,PMC3048347,21403800,NO-CC CODE,"Reactive oxygen species and thiol antioxidants, including glutathione (GSH), regulate innate immunity at various levels. This review outlines the redox-sensitive steps of the cellular mechanisms implicated in inflammation and host defense against infection, and describes how GSH is not only important as an antioxidant but also as a signaling molecule. There is an extensive literature of the role of GSH in immunity. Most reviews are biased by an oversimplified picture where “bad” free radicals cause all sorts of diseases and “good” antioxidants protect from them and prevent oxidative stress. While this may be the case in certain fields (eg, toxicology), the role of thiols (the topic of this review) in immunity certainly requires wearing scientist’s goggles and being prepared to accept a more complex picture. This review aims at describing the role of GSH in the lung in the context of immunity and inflammation. The first part summarizes the history and basic concepts of this picture. The second part focuses on GSH metabolism/levels in pathology, the third on the role of GSH in innate immunity and inflammation, and the fourth gives 4 examples describing the importance of GSH in the response to infections.",2011 Jan 25,"Ghezzi, Pietro",Int J Gen Med,,,True
49952f26e28224dcb6345f7bd9abcbc1b1dc32d8,PMC,Detection of novel astroviruses in urban brown rats and previously known astroviruses in humans,http://dx.doi.org/10.1099/vir.0.022764-0,PMC3052596,20554799,NO-CC CODE,"Several novel astroviruses have been recently discovered in humans and in other animals. Here, we report results from our surveillance of astroviruses in human and rodent faecal samples in Hong Kong. Classical human astroviruses (n=9) and a human MLB1 astrovirus were detected in human faecal samples (n=622). Novel astroviruses were detected from 1.6 % of the faecal samples of urban brown rat (Rattus norvegicus) (n=441), indicating the prevalence of astrovirus infection in rats might be much lower than that recently observed in bats. These rat astroviruses were phylogenetically related to recently discovered human astroviruses MLB1 and MLB2, suggesting that the MLB viruses and these novel rat astroviruses may share a common ancestor.",2010 Oct,"['Chu, Daniel K. W.', 'Chin, Alex W. H.', 'Smith, Gavin J.', 'Chan, Kwok-Hung', 'Guan, Yi', 'Peiris, J. S. Malik', 'Poon, Leo L. M.']",J Gen Virol,,,True
65fbc452a84534c7fd436616c2257fb81e9ea714,PMC,Detection of novel astroviruses in urban brown rats and previously known astroviruses in humans,http://dx.doi.org/10.1099/vir.0.022764-0,PMC3052596,20554799,NO-CC CODE,"Several novel astroviruses have been recently discovered in humans and in other animals. Here, we report results from our surveillance of astroviruses in human and rodent faecal samples in Hong Kong. Classical human astroviruses (n=9) and a human MLB1 astrovirus were detected in human faecal samples (n=622). Novel astroviruses were detected from 1.6 % of the faecal samples of urban brown rat (Rattus norvegicus) (n=441), indicating the prevalence of astrovirus infection in rats might be much lower than that recently observed in bats. These rat astroviruses were phylogenetically related to recently discovered human astroviruses MLB1 and MLB2, suggesting that the MLB viruses and these novel rat astroviruses may share a common ancestor.",2010 Oct,"['Chu, Daniel K. W.', 'Chin, Alex W. H.', 'Smith, Gavin J.', 'Chan, Kwok-Hung', 'Guan, Yi', 'Peiris, J. S. Malik', 'Poon, Leo L. M.']",J Gen Virol,,,False
a0cc0dc42e116ed81ab681809e67edadda9663c8,PMC,2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members,http://dx.doi.org/10.1038/nature09489,PMC3058805,21085181,NO-CC CODE,"Cellular mRNA of higher eukaryotes and many viral RNA are methylated at the N-7 and 2′-O positions of the 5′ guanosine cap by specific nuclear and cytoplasmic methyltransferases (MTases), respectively. Whereas N-7 methylation is essential for RNA translation and stability 1, the function of 2′-O methylation has remained uncertain since its discovery 35 years ago 2-4. Here, we show that a West Nile virus (WNV) mutant (E218A) that lacks 2′-O MTase activity was attenuated in wild type primary cells and mice but was pathogenic in the absence of type I interferon (IFN) signaling. 2′-O methylation of viral RNA did not affect IFN induction in WNV-infected fibroblasts but instead modulated the antiviral effects of IFN-induced proteins with tetratricopeptide repeats (IFIT), which are interferon-stimulated genes (ISG) implicated in regulation of protein translation. Poxvirus and coronavirus mutants that lacked 2′-O MTase activity similarly showed enhanced sensitivity to the antiviral actions of IFN and specifically, IFIT proteins. Our results demonstrate that the 2′-O methylation of the 5′ cap of viral RNA functions to subvert innate host antiviral responses through escape of IFIT-mediated suppression, and suggest an evolutionary explanation for 2′-O methylation of cellular mRNA: to distinguish self from non-self RNA. Differential methylation of cytoplasmic RNA likely serves as a paradigm for pattern recognition and restriction of propagation of foreign viral RNA in host cells.",2010 Nov 18,"['Daffis, Stephane', 'Szretter, Kristy J.', 'Schriewer, Jill', 'Li, Jianqing', 'Youn, Soonjeon', 'Errett, John', 'Lin, Tsai-Yu', 'Schneller, Stewart', 'Zust, Roland', 'Dong, Hongping', 'Thiel, Volker', 'Pierson, Theodore C.', 'Buller, R. Mark', 'Gale, Michael', 'Shi, Pei-Yong', 'Diamond, Michael S.']",Nature,,,True
2cd96b0ecf1e3ec1bab0923341f40aa1029db078,PMC,2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members,http://dx.doi.org/10.1038/nature09489,PMC3058805,21085181,NO-CC CODE,"Cellular mRNA of higher eukaryotes and many viral RNA are methylated at the N-7 and 2′-O positions of the 5′ guanosine cap by specific nuclear and cytoplasmic methyltransferases (MTases), respectively. Whereas N-7 methylation is essential for RNA translation and stability 1, the function of 2′-O methylation has remained uncertain since its discovery 35 years ago 2-4. Here, we show that a West Nile virus (WNV) mutant (E218A) that lacks 2′-O MTase activity was attenuated in wild type primary cells and mice but was pathogenic in the absence of type I interferon (IFN) signaling. 2′-O methylation of viral RNA did not affect IFN induction in WNV-infected fibroblasts but instead modulated the antiviral effects of IFN-induced proteins with tetratricopeptide repeats (IFIT), which are interferon-stimulated genes (ISG) implicated in regulation of protein translation. Poxvirus and coronavirus mutants that lacked 2′-O MTase activity similarly showed enhanced sensitivity to the antiviral actions of IFN and specifically, IFIT proteins. Our results demonstrate that the 2′-O methylation of the 5′ cap of viral RNA functions to subvert innate host antiviral responses through escape of IFIT-mediated suppression, and suggest an evolutionary explanation for 2′-O methylation of cellular mRNA: to distinguish self from non-self RNA. Differential methylation of cytoplasmic RNA likely serves as a paradigm for pattern recognition and restriction of propagation of foreign viral RNA in host cells.",2010 Nov 18,"['Daffis, Stephane', 'Szretter, Kristy J.', 'Schriewer, Jill', 'Li, Jianqing', 'Youn, Soonjeon', 'Errett, John', 'Lin, Tsai-Yu', 'Schneller, Stewart', 'Zust, Roland', 'Dong, Hongping', 'Thiel, Volker', 'Pierson, Theodore C.', 'Buller, R. Mark', 'Gale, Michael', 'Shi, Pei-Yong', 'Diamond, Michael S.']",Nature,,,False
f9a57bac5e3280f475b1e3ba90c7a5610e917aef,PMC,2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members,http://dx.doi.org/10.1038/nature09489,PMC3058805,21085181,NO-CC CODE,"Cellular mRNA of higher eukaryotes and many viral RNA are methylated at the N-7 and 2′-O positions of the 5′ guanosine cap by specific nuclear and cytoplasmic methyltransferases (MTases), respectively. Whereas N-7 methylation is essential for RNA translation and stability 1, the function of 2′-O methylation has remained uncertain since its discovery 35 years ago 2-4. Here, we show that a West Nile virus (WNV) mutant (E218A) that lacks 2′-O MTase activity was attenuated in wild type primary cells and mice but was pathogenic in the absence of type I interferon (IFN) signaling. 2′-O methylation of viral RNA did not affect IFN induction in WNV-infected fibroblasts but instead modulated the antiviral effects of IFN-induced proteins with tetratricopeptide repeats (IFIT), which are interferon-stimulated genes (ISG) implicated in regulation of protein translation. Poxvirus and coronavirus mutants that lacked 2′-O MTase activity similarly showed enhanced sensitivity to the antiviral actions of IFN and specifically, IFIT proteins. Our results demonstrate that the 2′-O methylation of the 5′ cap of viral RNA functions to subvert innate host antiviral responses through escape of IFIT-mediated suppression, and suggest an evolutionary explanation for 2′-O methylation of cellular mRNA: to distinguish self from non-self RNA. Differential methylation of cytoplasmic RNA likely serves as a paradigm for pattern recognition and restriction of propagation of foreign viral RNA in host cells.",2010 Nov 18,"['Daffis, Stephane', 'Szretter, Kristy J.', 'Schriewer, Jill', 'Li, Jianqing', 'Youn, Soonjeon', 'Errett, John', 'Lin, Tsai-Yu', 'Schneller, Stewart', 'Zust, Roland', 'Dong, Hongping', 'Thiel, Volker', 'Pierson, Theodore C.', 'Buller, R. Mark', 'Gale, Michael', 'Shi, Pei-Yong', 'Diamond, Michael S.']",Nature,,,True
3858fd802f76401901ec985a5996b77319299098,PMC,"Peptide model helices in lipid membranes: insertion, positioning, and lipid response on aggregation studied by X-ray scattering",http://dx.doi.org/10.1007/s00249-010-0645-4,PMC3070074,21181143,NO-CC CODE,"Studying membrane active peptides or protein fragments within the lipid bilayer environment is particularly challenging in the case of synthetically modified, labeled, artificial, or recently discovered native structures. For such samples the localization and orientation of the molecular species or probe within the lipid bilayer environment is the focus of research prior to an evaluation of their dynamic or mechanistic behavior. X-ray scattering is a powerful method to study peptide/lipid interactions in the fluid, fully hydrated state of a lipid bilayer. For one, the lipid response can be revealed by observing membrane thickening and thinning as well as packing in the membrane plane; at the same time, the distinct positions of peptide moieties within lipid membranes can be elucidated at resolutions of up to several angstroms by applying heavy-atom labeling techniques. In this study, we describe a generally applicable X-ray scattering approach that provides robust and quantitative information about peptide insertion and localization as well as peptide/lipid interaction within highly oriented, hydrated multilamellar membrane stacks. To this end, we have studied an artificial, designed β-helical peptide motif in its homodimeric and hairpin variants adopting different states of oligomerization. These peptide lipid complexes were analyzed by grazing incidence diffraction (GID) to monitor changes in the lateral lipid packing and ordering. In addition, we have applied anomalous reflectivity using synchrotron radiation as well as in-house X-ray reflectivity in combination with iodine-labeling in order to determine the electron density distribution ρ(z) along the membrane normal (z axis), and thereby reveal the hydrophobic mismatch situation as well as the position of certain amino acid side chains within the lipid bilayer. In the case of multiple labeling, the latter technique is not only applicable to demonstrate the peptide’s reconstitution but also to generate evidence about the relative peptide orientation with respect to the lipid bilayer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00249-010-0645-4) contains supplementary material, which is available to authorized users.",2011 Apr 23,"['Schneggenburger, Philipp E.', 'Beerlink, André', 'Weinhausen, Britta', 'Salditt, Tim', 'Diederichsen, Ulf']",Eur Biophys J,,,True
5e1017f2def4ac50f1b63bd52a9a2214c1dfd3b7,PMC,"Peptide model helices in lipid membranes: insertion, positioning, and lipid response on aggregation studied by X-ray scattering",http://dx.doi.org/10.1007/s00249-010-0645-4,PMC3070074,21181143,NO-CC CODE,"Studying membrane active peptides or protein fragments within the lipid bilayer environment is particularly challenging in the case of synthetically modified, labeled, artificial, or recently discovered native structures. For such samples the localization and orientation of the molecular species or probe within the lipid bilayer environment is the focus of research prior to an evaluation of their dynamic or mechanistic behavior. X-ray scattering is a powerful method to study peptide/lipid interactions in the fluid, fully hydrated state of a lipid bilayer. For one, the lipid response can be revealed by observing membrane thickening and thinning as well as packing in the membrane plane; at the same time, the distinct positions of peptide moieties within lipid membranes can be elucidated at resolutions of up to several angstroms by applying heavy-atom labeling techniques. In this study, we describe a generally applicable X-ray scattering approach that provides robust and quantitative information about peptide insertion and localization as well as peptide/lipid interaction within highly oriented, hydrated multilamellar membrane stacks. To this end, we have studied an artificial, designed β-helical peptide motif in its homodimeric and hairpin variants adopting different states of oligomerization. These peptide lipid complexes were analyzed by grazing incidence diffraction (GID) to monitor changes in the lateral lipid packing and ordering. In addition, we have applied anomalous reflectivity using synchrotron radiation as well as in-house X-ray reflectivity in combination with iodine-labeling in order to determine the electron density distribution ρ(z) along the membrane normal (z axis), and thereby reveal the hydrophobic mismatch situation as well as the position of certain amino acid side chains within the lipid bilayer. In the case of multiple labeling, the latter technique is not only applicable to demonstrate the peptide’s reconstitution but also to generate evidence about the relative peptide orientation with respect to the lipid bilayer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00249-010-0645-4) contains supplementary material, which is available to authorized users.",2011 Apr 23,"['Schneggenburger, Philipp E.', 'Beerlink, André', 'Weinhausen, Britta', 'Salditt, Tim', 'Diederichsen, Ulf']",Eur Biophys J,,,True
eee925fdf6e8c99bb72678f1b413fd65cc78c585,PMC,Antibody-Mediated “Universal” Osteoclast Targeting Platform using Calcitonin as a Model Drug,http://dx.doi.org/10.1007/s11095-011-0376-y,PMC3073043,21301934,NO-CC CODE,"PURPOSE: To generate and characterize a specific monoclonal antibody (mAb) against recombinant human RANK receptor and to develop an antiresorptive strategy using this mAb as an osteoclast-targeting platform that selectively targets osteoclast cells whilst delivering an attached (i.e. chemically conjugated) active drug cargo. METHODS: Using hybridoma technology, we generated a specific monoclonal antibody (mAb) against recombinant human RANK receptor and characterized by SDS PAGE, ELISA, Western Blot and immunocytochemistry, then synthesized osteoclast-targeting bioconjugates of salmon calcitonin (sCT) using this antibody by generating thiol groups on mAb using 2-Iminothiolane and subsequently reacting them with sCT-PEG-MAL synthesised from sCT and NHS-PEG-MAL. To test the efficacy of the conjugate in vitro, osteoclasts were generated from precursor RAW 264.7 cells by dosing with the cytokines macrophage-colony-stimulating factor (M-CSF), and RANK Ligand (RANKL) and TRAP activity assay, Resorption Pit Assay, TRAP staining were performed. Cytotoxicity of the mAb-sCT conjugate was also evaluated in RAW 264.7 cells; sCT bioactivity and CTR binding potential were evaluated by in vitro intracellular cAMP stimulation assay in human T47D breast cancer cells. RESULTS: Generation of antibody against human RANK receptor was confirmed by SDS PAGE, ELISA and Western Blot. Immunocytochemistry confirmed the osteoclast targeting potential of the antibody. Successful conjugation of the antibody with sCT was confirmed by SDS PAGE and ELISA.Multinucleated osteoclast formation was confirmed by staining for tartrate-resistant acid phosphatase (TRAP). Conjugate functionality was confirmed by TRAP activity and Resorption Pit assay, showing the inhibitory effect on osteoclast differentiation. cAMP assay confirmed the retention of calcitonin bioactivity after conjugation. CONCLUSIONS: Our strategy offers the potential for a “universal” osteoclast-targeting platform—one that targets the RANK receptor on osteoclast cells by simply altering the conjugated cargo in order to affect the specific regulation of osteoclast cells.",2011 May 8,"['Newa, Madhuri', 'Bhandari, Krishna Hari', 'Tang, Lili', 'Kalvapalle, Rohit', 'Suresh, Mavanur', 'Doschak, Michael R.']",Pharm Res,,,True
fa38f89cd6981199ac346529620337c743e4aada,PMC,Wresting SARS from Uncertainty,http://dx.doi.org/10.3201/eid1002.031032,PMC3086179,15040341,NO-CC CODE,,2004 Feb,"['Lingappa, Jairam R.', 'McDonald, L. Clifford', 'Simone, Patricia', 'Parashar, Umesh']",Emerg Infect Dis,,,True
1b18bebba1cbb0fdf78888bf15d03ac44c1582af,PMC,Rhinovirus C and Respiratory Exacerbations in Children with Cystic Fibrosis,http://dx.doi.org/10.3201/eid1606.100063,PMC3086221,20507756,NO-CC CODE,"To investigate a possible role for human rhinovirus C in respiratory exacerbations of children with cystic fibrosis, we conducted microbiologic testing on respiratory specimens from 103 such patients in São Paulo, Brazil, during 2006–2007. A significant association was found between the presence of human rhinovirus C and respiratory exacerbations.",2010 Jun,"['de Almeida, Marina B.', 'Zerbinati, Rodrigo M.', 'Tateno, Adriana F.', 'Oliveira, Cristina M.', 'Romão, Renata M.', 'Rodrigues, Joaquim C.', 'Pannuti, Cláudio S.', 'da Silva Filho, Luiz Vicente F.']",Emerg Infect Dis,,,True
cabbf64c0fcdcb3cfff6df2101a6b8c77c02e4f6,PMC,Novel Betaherpesvirus in Bats,http://dx.doi.org/10.3201/eid1606.091567,PMC3086227,20507753,NO-CC CODE,"Because bats are associated with emerging zoonoses, identification and characterization of novel viruses from bats is needed. Using a modified rapid determination system for viral RNA/DNA sequences, we identified a novel bat betaherpesvirus 2 not detected by herpesvirus consensus PCR. This modified system is useful for detecting unknown viruses.",2010 Jun,"['Watanabe, Shumpei', 'Maeda, Ken', 'Suzuki, Kazuo', 'Ueda, Naoya', 'Iha, Koichiro', 'Taniguchi, Satoshi', 'Shimoda, Hiroshi', 'Kato, Kentaro', 'Yoshikawa, Yasuhiro', 'Morikawa, Shigeru', 'Kurane, Ichiro', 'Akashi, Hiroomi', 'Mizutani, Tetsuya']",Emerg Infect Dis,,,True
64778c71390d68e402c5999fcfd3eb8723cdaf49,PMC,Novel Betaherpesvirus in Bats,http://dx.doi.org/10.3201/eid1606.091567,PMC3086227,20507753,NO-CC CODE,"Because bats are associated with emerging zoonoses, identification and characterization of novel viruses from bats is needed. Using a modified rapid determination system for viral RNA/DNA sequences, we identified a novel bat betaherpesvirus 2 not detected by herpesvirus consensus PCR. This modified system is useful for detecting unknown viruses.",2010 Jun,"['Watanabe, Shumpei', 'Maeda, Ken', 'Suzuki, Kazuo', 'Ueda, Naoya', 'Iha, Koichiro', 'Taniguchi, Satoshi', 'Shimoda, Hiroshi', 'Kato, Kentaro', 'Yoshikawa, Yasuhiro', 'Morikawa, Shigeru', 'Kurane, Ichiro', 'Akashi, Hiroomi', 'Mizutani, Tetsuya']",Emerg Infect Dis,,,True
96b4ff3646d9229fa7d420908f6507f5b746e270,PMC,Novel Betaherpesvirus in Bats,http://dx.doi.org/10.3201/eid1606.091567,PMC3086227,20507753,NO-CC CODE,"Because bats are associated with emerging zoonoses, identification and characterization of novel viruses from bats is needed. Using a modified rapid determination system for viral RNA/DNA sequences, we identified a novel bat betaherpesvirus 2 not detected by herpesvirus consensus PCR. This modified system is useful for detecting unknown viruses.",2010 Jun,"['Watanabe, Shumpei', 'Maeda, Ken', 'Suzuki, Kazuo', 'Ueda, Naoya', 'Iha, Koichiro', 'Taniguchi, Satoshi', 'Shimoda, Hiroshi', 'Kato, Kentaro', 'Yoshikawa, Yasuhiro', 'Morikawa, Shigeru', 'Kurane, Ichiro', 'Akashi, Hiroomi', 'Mizutani, Tetsuya']",Emerg Infect Dis,,,False
d01690bafbc4c042dd47c6aa77801b56071493d2,PMC,"Oseltamivir-Resistant Influenza Viruses A (H1N1) during 2007–2009 Influenza Seasons, Japan",http://dx.doi.org/10.3201/eid1606.091623,PMC3086245,20507742,NO-CC CODE,"To monitor oseltamivir-resistant influenza viruses A (H1N1) (ORVs) with H275Y in neuraminidase (NA) in Japan during 2 influenza seasons, we analyzed 3,216 clinical samples by NA sequencing and/or NA inhibition assay. The total frequency of ORVs was 2.6% (45/1,734) during the 2007–08 season and 99.7% (1,477/1,482) during the 2008–09 season, indicating a marked increase in ORVs in Japan during 1 influenza season. The NA gene of ORVs in the 2007–08 season fell into 2 distinct lineages by D354G substitution, whereas that of ORVs in the 2008–09 season fell into 1 lineage. NA inhibition assay and M2 sequencing showed that almost all the ORVs were sensitive to zanamivir and amantadine. The hemagglutination inhibition test showed that ORVs were antigenetically similar to the 2008–09 vaccine strain A/Brisbane/59/2007. Our data indicate that the current vaccine or zanamivir and amantadine are effective against recent ORVs, but continuous surveillance remains necessary.",2010 Jun,"['Ujike, Makoto', 'Shimabukuro, Kozue', 'Mochizuki, Kiku', 'Obuchi, Masatsugu', 'Kageyama, Tsutomu', 'Shirakura, Masayuki', 'Kishida, Noriko', 'Yamashita, Kazuyo', 'Horikawa, Hiroshi', 'Kato, Yumiko', 'Fujita, Nobuyuki', 'Tashiro, Masato', 'Odagiri, Takato', None]",Emerg Infect Dis,,,True
f2cf26f9c677482ee8e060ce7d9d73b6214fef52,PMC,Novel Norovirus in Dogs with Diarrhea,http://dx.doi.org/10.3201/eid1606.091861,PMC3086253,20507751,NO-CC CODE,"To identify the prevalence and genetic variability of noroviruses in dogs, we tested fecal samples by using reverse transcription–PCR. We found canine norovirus in 40% and 9% of dogs with and without diarrhea, respectively. The virus was genetically unrelated to other noroviruses and constitutes a tentative new genogroup.",2010 Jun,"['Mesquita, João Rodrigo', 'Barclay, Leslie', 'Nascimento, Maria São José', 'Vinjé, Jan']",Emerg Infect Dis,,,True
c6463593f45c19d4989336f52905704d1ec9b74e,PMC,The Influence of Social-Cognitive Factors on Personal Hygiene Practices to Protect Against Influenzas: Using Modelling to Compare Avian A/H5N1 and 2009 Pandemic A/H1N1 Influenzas in Hong Kong,http://dx.doi.org/10.1007/s12529-010-9123-8,PMC3088805,20949342,NO-CC CODE,"BACKGROUND: Understanding population responses to influenza helps optimize public health interventions. Relevant theoretical frameworks remain nascent. PURPOSE: To model associations between trust in information, perceived hygiene effectiveness, knowledge about the causes of influenza, perceived susceptibility and worry, and personal hygiene practices (PHPs) associated with influenza. METHODS: Cross-sectional household telephone surveys on avian influenza A/H5N1 (2006) and pandemic influenza A/H1N1 (2009) gathered comparable data on trust in formal and informal sources of influenza information, influenza-related knowledge, perceived hygiene effectiveness, worry, perceived susceptibility, and PHPs. Exploratory factor analysis confirmed domain content while confirmatory factor analysis was used to evaluate the extracted factors. The hypothesized model, compiled from different theoretical frameworks, was optimized with structural equation modelling using the A/H5N1 data. The optimized model was then tested against the A/H1N1 dataset. RESULTS: The model was robust across datasets though corresponding path weights differed. Trust in formal information was positively associated with perceived hygiene effectiveness which was positively associated with PHPs in both datasets. Trust in formal information was positively associated with influenza worry in A/H5N1 data, and with knowledge of influenza cause in A/H1N1 data, both variables being positively associated with PHPs. Trust in informal information was positively associated with influenza worry in both datasets. Independent of information trust, perceived influenza susceptibility associated with influenza worry. Worry associated with PHPs in A/H5N1 data only. CONCLUSIONS: Knowledge of influenza cause and perceived PHP effectiveness were associated with PHPs. Improving trust in formal information should increase PHPs. Worry was significantly associated with PHPs in A/H5N1.",2011 Jun 15,"['Liao, Qiuyan', 'Cowling, Benjamin J.', 'Lam, Wendy Wing Tak', 'Fielding, Richard']",Int J Behav Med,,,True
5aefd421655e2155dfc6a2fcb3c12dc14f35e9dc,PMC,"Severe Acute Respiratory Syndrome, Beijing, 2003",http://dx.doi.org/10.3201/eid1001.030553,PMC3092360,15078593,NO-CC CODE,"The largest outbreak of severe acute respiratory syndrome (SARS) struck Beijing in spring 2003. Multiple importations of SARS to Beijing initiated transmission in several healthcare facilities. Beijing’s outbreak began March 5; by late April, daily hospital admissions for SARS exceeded 100 for several days; 2,521 cases of probable SARS occurred. Attack rates were highest in those 20–39 years of age; 1% of cases occurred in children <10 years. The case-fatality rate was highest among patients >65 years (27.7% vs. 4.8% for those 20–64 years, p < 0.001). Healthcare workers accounted for 16% of probable cases. The proportion of case-patients without known contact to a SARS patient increased significantly in May. Implementation of early detection, isolation, contact tracing, quarantine, triage of case-patients to designated SARS hospitals, and community mobilization ended the outbreak.",2004 Jan,"['Liang, Wannian', 'Zhu, Zonghan', 'Guo, Jiyong', 'Liu, Zejun', 'He, Xiong', 'Zhou, Weigong', 'Chin, Daniel P.', 'Schuchat, Anne', None]",Emerg Infect Dis,,,True
99ad07c4a0fdcc24df76b723ff978c84076c56ac,PMC,One-year molecular survey of astrovirus infection in turkeys in Poland,http://dx.doi.org/10.1007/s00705-011-0958-3,PMC3104002,21404112,NO-CC CODE,"The presence of turkey astrovirus (TAstV) was monitored in meat-type turkey flocks in Poland in 2008. Clinical samples (10 individual faecal swabs/flock) from 77 flocks aged 1-19 weeks were collected from different regions of the country. RT-PCR experiments were performed for detection and molecular characterization of TAstV using four sets of primers within the RdRp gene (ORF1b). The prevalence of astrovirus was 34/77 (44.15%) in the flocks tested. TAstV type 2 was associated with 30 of 77 infections (38.9%), either alone or in mixed infections; TAstV type 1 was detected in 9 of 77 flocks (11.6%), either alone or in mixed infections; ANV was detected only in one flock (1.29%) by sequence analysis during this study. Phylogenetic analysis revealed genetic variability in the TAstV strains that were isolated. Some of Polish TAstV-2 strains were genetically related to the North American isolates; however, most of them formed a distinct subgroup of “European” isolates, suggesting their separate origin or evolution. Additionally, due to the high variability of the TAstV sequences, the most suitable method for TAstV typing seems to be sequencing.",2011 Jun 15,"['Domanska-Blicharz, Katarzyna', 'Seroka, Anna', 'Minta, Zenon']",Arch Virol,,,True
4691c2e3a8705236b9eb901abfbca15fc89773da,PMC,Initial human transmission dynamics of the pandemic (H1N1) 2009 virus in North America,http://dx.doi.org/10.1111/j.1750-2659.2009.00100.x,PMC3122129,19702583,NO-CC CODE,"Background  Between 5 and 25 April 2009, pandemic (H1N1) 2009 caused a substantial, severe outbreak in Mexico, and subsequently developed into the first global pandemic in 41 years. We determined the reproduction number of pandemic (H1N1) 2009 by analyzing the dynamics of the complete case series in Mexico City during this early period. Methods  We analyzed three mutually exclusive datasets from Mexico City Distrito Federal which constituted all suspect cases from 15 March to 25 April: confirmed pandemic (H1N1) 2009 infections, non‐pandemic influenza A infections and patients who tested negative for influenza. We estimated the initial reproduction number from 497 suspect cases identified prior to 20 April, using a novel contact network methodology incorporating dates of symptom onset and hospitalization, variation in contact rates, extrinsic sociological factors, and uncertainties in underreporting and disease progression. We tested the robustness of this estimate using both the subset of laboratory‐confirmed pandemic (H1N1) 2009 infections and an extended case series through 25 April, adjusted for suspected ascertainment bias. Results  The initial reproduction number (95% confidence interval range) for this novel virus is 1·51 (1·32–1·71) based on suspected cases and 1·43 (1·29–1·57) based on confirmed cases before 20 April. The longer time series (through 25 April) yielded a higher estimate of 2·04 (1·84–2·25), which reduced to 1·44 (1·38–1·51) after correction for ascertainment bias. Conclusions  The estimated transmission characteristics of pandemic (H1N1) 2009 suggest that pharmaceutical and non‐pharmaceutical mitigation measures may appreciably limit its spread prior the development of an effective vaccine.",2009 Sep 18,"['Pourbohloul, Babak', 'Ahued, Armando', 'Davoudi, Bahman', 'Meza, Rafael', 'Meyers, Lauren A.', 'Skowronski, Danuta M.', 'Villaseñor, Ignacio', 'Galván, Fernando', 'Cravioto, Patricia', 'Earn, David J. D.', 'Dushoff, Jonathan', 'Fisman, David', 'Edmunds, W. John', 'Hupert, Nathaniel', 'Scarpino, Samuel V.', 'Trujillo, Jesús', 'Lutzow, Miguel', 'Morales, Jorge', 'Contreras, Ada', 'Chávez, Carolina', 'Patrick, David M.', 'Brunham, Robert C.']",Influenza Other Respir Viruses,,,True
5c59d9e3c66ccee9b1e671f475954e581af7a320,PMC,Mucosal Immunization Induces a Higher Level of Lasting Neutralizing Antibody Response in Mice by a Replication-Competent Smallpox Vaccine: Vaccinia Tiantan Strain,http://dx.doi.org/10.1155/2011/970424,PMC3134386,21765641,NO-CC CODE,"The possible bioterrorism threat using the variola virus, the causative agent of smallpox, has promoted us to further investigate the immunogenicity profiles of existing vaccines. Here, we study for the first time the immunogenicity profile of a replication-competent smallpox vaccine (vaccinia Tiantan, VTT strain) for inducing neutralizing antibodies (Nabs) through mucosal vaccination, which is noninvasive and has a critical implication for massive vaccination programs. Four different routes of vaccination were tested in parallel including intramuscular (i.m.), intranasal (i.n.), oral (i.o.), and subcutaneous (s.c.) inoculations in mice. We found that one time vaccination with an optimal dose of VTT was able to induce anti-VTT Nabs via each of the four routes. Higher levels of antiviral Nabs, however, were induced via the i.n. and i.o. inoculations when compared with the i.m. and s.c. routes. Moreover, the i.n. and i.o. vaccinations also induced higher sustained levels of Nabs overtime, which conferred better protections against homologous or alternating mucosal routes of viral challenges six months post vaccination. The VTT-induced immunity via all four routes, however, was partially effective against the intramuscular viral challenge. Our data have implications for understanding the potential application of mucosal smallpox vaccination and for developing VTT-based vaccines to overcome preexisting antivaccinia immunity.",2011 Jun 20,"['Lu, Bin', 'Yu, Wenbo', 'Huang, Xiaoxing', 'Wang, Haibo', 'Liu, Li', 'Chen, Zhiwei']",J Biomed Biotechnol,,,True
d7011047894121dc7f115cbeb1f355b76c33f80d,PMC,A Brief Review on Diagnosis of Foot-and-Mouth Disease of Livestock: Conventional to Molecular Tools,http://dx.doi.org/10.4061/2011/905768,PMC3135314,21776357,NO-CC CODE,"Foot-and-mouth disease (FMD) is one of the highly contagious diseases of domestic animals. Effective control of this disease needs sensitive, specific, and quick diagnostic tools at each tier of control strategy. In this paper we have outlined various diagnostic approaches from old to new generation in a nutshell. Presently FMD diagnosis is being carried out using techniques such as Virus Isolation (VI), Sandwich-ELISA (S-ELISA), Liquid-Phase Blocking ELISA (LPBE), Multiplex-PCR (m-PCR), and indirect ELISA (DIVA), and real time-PCR can be used for detection of antibody against nonstructural proteins. Nucleotide sequencing for serotyping, microarray as well as recombinant antigen-based detection, biosensor, phage display, and nucleic-acid-based diagnostic are on the way for rapid and specific detection of FMDV. Various pen side tests, namely, lateral flow, RT-LAMP, Immunostrip tests, and so forth. are also developed for detection of the virus in field condition.",2011 Jul 6,"['Longjam, Neeta', 'Deb, Rajib', 'Sarmah, A. K.', 'Tayo, Tilling', 'Awachat, V. B.', 'Saxena, V. K.']",Vet Med Int,,,True
2a2f98e53f7347072c5d8975d76acfa5da084905,PMC,Renewed Global Partnerships and Redesigned Roadmaps for Rabies Prevention and Control,http://dx.doi.org/10.4061/2011/923149,PMC3135331,21776359,NO-CC CODE,"Canine rabies, responsible for most human rabies deaths, is a serious global public health concern. This zoonosis is entirely preventable, but by focusing solely upon rabies prevention in humans, this “incurable wound” persists at high costs. Although preventing human deaths through canine rabies elimination is feasible, dog rabies control is often neglected, because dogs are not considered typical economic commodities by the animal health sector. Here, we demonstrate that the responsibility of managing rabies falls upon multiple sectors, that a truly integrated approach is the key to rabies elimination, and that considerable progress has been made to this effect. Achievements include the construction of global rabies networks and organizational partnerships; development of road maps, operational toolkits, and a blueprint for rabies prevention and control; and opportunities for scaling up and replication of successful programs. Progress must continue towards overcoming the remaining challenges preventing the ultimate goal of rabies elimination.",2011 Jun 1,"['Lembo, Tiziana', 'Attlan, Michaël', 'Bourhy, Hervé', 'Cleaveland, Sarah', 'Costa, Peter', 'de Balogh, Katinka', 'Dodet, Betty', 'Fooks, Anthony R.', 'Hiby, Elly', 'Leanes, Fernando', 'Meslin, François-Xavier', 'Miranda, Mary Elizabeth', 'Müller, Thomas', 'Nel, Louis H.', 'Rupprecht, Charles E.', 'Tordo, Noël', 'Tumpey, Abbigail', 'Wandeler, Alexander', 'Briggs, Deborah J.']",Vet Med Int,,,True
134953face0c7475092ed130a40ebd194b99358b,PMC,Geometry and Adhesion of Extracellular Domains of DC-SIGNR Neck Length Variants Analyzed by Force–Distance Measurements,http://dx.doi.org/10.1021/bi2003444,PMC3140775,21650186,NO-CC CODE,"[Image: see text] Force–distance measurements have been used to examine differences in the interaction of the dendritic cell glycan-binding receptor DC-SIGN and the closely related endothelial cell receptor DC-SIGNR (L-SIGN) with membranes bearing glycan ligands. The results demonstrate that upon binding to membrane-anchored ligand, DC-SIGNR undergoes a conformational change similar to that previously observed for DC-SIGN. The results also validate a model for the extracellular domain of DC-SIGNR derived from crystallographic studies. Force measurements were performed with DC-SIGNR variants that differ in the length of the neck that result from genetic polymorphisms, which encode different numbers of the 23-amino acid repeat sequences that constitute the neck. The findings are consistent with an elongated, relatively rigid structure of the neck repeat observed in crystals. In addition, differences in the lengths of DC-SIGN and DC-SIGNR extracellular domains with equivalent numbers of neck repeats support a model in which the different dispositions of the carbohydrate-recognition domains in DC-SIGN and DC-SIGNR result from variations in the sequences of the necks.",2011 Jul 12,"['Leckband, Deborah E.', 'Menon, Sindhu', 'Rosenberg, Kenneth', 'Graham, Sarah A.', 'Taylor, Maureen E.', 'Drickamer, Kurt']",Biochemistry,,,True
089cb93cd18fdf78c9f6b99409151919980b6ace,PMC,Geometry and Adhesion of Extracellular Domains of DC-SIGNR Neck Length Variants Analyzed by Force–Distance Measurements,http://dx.doi.org/10.1021/bi2003444,PMC3140775,21650186,NO-CC CODE,"[Image: see text] Force–distance measurements have been used to examine differences in the interaction of the dendritic cell glycan-binding receptor DC-SIGN and the closely related endothelial cell receptor DC-SIGNR (L-SIGN) with membranes bearing glycan ligands. The results demonstrate that upon binding to membrane-anchored ligand, DC-SIGNR undergoes a conformational change similar to that previously observed for DC-SIGN. The results also validate a model for the extracellular domain of DC-SIGNR derived from crystallographic studies. Force measurements were performed with DC-SIGNR variants that differ in the length of the neck that result from genetic polymorphisms, which encode different numbers of the 23-amino acid repeat sequences that constitute the neck. The findings are consistent with an elongated, relatively rigid structure of the neck repeat observed in crystals. In addition, differences in the lengths of DC-SIGN and DC-SIGNR extracellular domains with equivalent numbers of neck repeats support a model in which the different dispositions of the carbohydrate-recognition domains in DC-SIGN and DC-SIGNR result from variations in the sequences of the necks.",2011 Jul 12,"['Leckband, Deborah E.', 'Menon, Sindhu', 'Rosenberg, Kenneth', 'Graham, Sarah A.', 'Taylor, Maureen E.', 'Drickamer, Kurt']",Biochemistry,,,False
c164cfe5a21b1f6a0efb61aa0e8bdf34efb93867,PMC,Viral Takeover of the Host Ubiquitin System,http://dx.doi.org/10.3389/fmicb.2011.00161,PMC3147166,21847386,NO-CC CODE,"Like the other more well-characterized post-translational modifications (phosphorylation, methylation, acetylation, acylation, etc.), the attachment of the 76 amino acid ubiquitin (Ub) protein to substrates has been shown to govern countless cellular processes. As obligate intracellular parasites, viruses have evolved the capability to commandeer many host processes in order to maximize their own survival, whether it be to increase viral production or to ensure the long-term survival of latently infected host cells. The first evidence that viruses could usurp the Ub system came from the DNA tumor viruses and Adenoviruses, each of which use Ub to dysregulate the host cell cycle (Scheffner et al., 1990; Querido et al., 2001). Today, the list of viruses that utilize Ub includes members from almost every viral class, encompassing both RNA and DNA viruses. Among these, there are examples of Ub usage at every stage of the viral life cycle, involving both ubiquitination and de-ubiquitination. In addition to viruses that merely modify the host Ub system, many of the large DNA viruses encode their own Ub modifying machinery. In this review, we highlight the latest discoveries regarding the myriad ways that viruses utilize Ub to their advantage.",2011 Jul 28,"['Gustin, Jean K.', 'Moses, Ashlee V.', 'Früh, Klaus', 'Douglas, Janet L.']",Front Microbiol,,,True
4a3941003ea2673397975ae8bc2536ad59f789e5,PMC,Evaluation of admissions to the Major Incident Hospital based on a standardized protocol,http://dx.doi.org/10.1007/s00068-010-0067-0,PMC3150834,21837255,NO-CC CODE,"INTRODUCTION: The Major Incident Hospital (MIH) is a unique facility strictly reserved to provide immediate large-scale emergency care for victims of disasters and major incidents. We evaluated the implemented organization to identify strengths and weaknesses, and provide knowledge essential for further improvement of preparedness. METHOD: According to the Protocol for Reports from Major accidents and Disasters (PRMD) and along with our five scenarios for activation, we analyzed all the data from evaluation reports of all our deployments since the MIH was founded in 1991. RESULTS: The MIH was able to provide group-wise emergency care to military (29 admissions) as well as civilian victims of major incidents and disasters, both national (260) and international (226). Group-wise treatment was advantageous for quarantine, logistics, registration, emotional support and (pre)arrangements for family, media and security. Strong points are preparedness and availability of a dedicated facility, including ICU, X-ray and OR facilities, irrespective of MRSA status and prearranged cooperation, e.g., with a trauma centre, poison centre and the military. Evaluation, research and training resulted in a barcode registration system and continuous adaptations to improve preparedness. Shortage of resources did not occur; use of the MIH’s available resources for national incidents though, could be further optimized. CONCLUSIONS: Recommendations for the future are: improvement of imbedding in regional and national procedures, continued dedicated time and staff for training, research and development, improvement of nuclear/biological/chemical decontamination facilities and preparedness, implementation of standardized scoring systems and expansion of registration systems to the prehospital setting. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00068-010-0067-0) contains supplementary material, which is available to authorized users.",2011 Feb 3,"['Marres, G. M. H.', 'van der Eijk, J.', 'Bemelman, M.', 'Leenen, L. P. H.']",Eur J Trauma Emerg Surg,,,True
60b35dbca96ef8c02f90e2aaad56e19bdd150cf6,PMC,Histological study of the biodynamics of iron oxide nanoparticles with different diameters,http://dx.doi.org/10.2147/IJN.S22189,PMC3152477,21845049,NO-CC CODE,"The biodynamics of ultrasmall and small superparamagnetic iron oxide (USPIO and SPIO, respectively) particles that were injected intraperitoneally into 36 C57BL/6 mice were investigated chronologically. Their distribution was studied histologically at six time points by measuring iron-positive areas (μm(2)) in organ sections stained with Prussian blue. The uptake of the differently sized particles was also compared by cultured murine macrophages (J774.1). Iron-positive areas in the liver were significantly larger in the mice injected with USPIO than those injected with SPIO at the first three time points (P < 0.05). The amount of USPIO in the lung parenchyma around the airway was larger than that of SPIO at four time points (P < 0.05); distribution to the lymph nodes was not significantly different. The amount of iron was significantly larger in SPIO- than USPIO-treated cultured cells (P < 0.05). In conclusion, it is suggested that intra peritoneally injected USPIO particles could be used more quickly than SPIO to make Kupffer images of the liver and that both agents could help get lymph node images of similar quality.",2011 Aug 2,"['Tsuchiya, Keiko', 'Nitta, Norihisa', 'Sonoda, Akinaga', 'Nitta-Seko, Ayumi', 'Ohta, Shinichi', 'Otani, Hideji', 'Takahashi, Masashi', 'Murata, Kiyoshi', 'Murase, Katsutoshi', 'Nohara, Satoshi', 'Mukaisho, Kenichi']",Int J Nanomedicine,,,True
ab343259d4d09f7bc3e154063755e18d3ffed609,PMC,An Updated Loop-Mediated Isothermal Amplification Method for Rapid Diagnosis of H5N1 Avian Influenza Viruses,http://dx.doi.org/10.2149/tmh.2010-21,PMC3153145,22028606,NO-CC CODE,"We designed a new set of primers for reverse transcriptase loop-mediated isothermal amplification (RTLAMP) to specifically amplify the HA gene of avian influenza viruses subtype H5N1. By testing nine H5N1 virus strains and 41 clinical samples collected in Northern Vietnam, we found that the new primers showed higher sensitivity and specificity than the previously published RT-LAMP primers and were comparable to the RT-PCR method currently recommended by WHO. These results suggest that our RT-LAMP assay may be a better choice as a diagnostic tool for current H5N1 influenza virus infection.",2011 Mar 24,"['Dinh, Duc Tuan', 'Le, Mai Thi Quynh', 'Vuong, Cuong Duc', 'Hasebe, Futoshi', 'Morita, Kouichi']",Trop Med Health,,,True
b18e1ab81f9263fe8f2ec5bec5c54c31371f4a4c,PMC,Delivery Systems for In Vivo Use of Nucleic Acid Drugs,,PMC3155220,21901073,NO-CC CODE,"The notorious biotechnological advance of the last few decades has allowed the development of experimental methods for understanding molecular mechanisms of genes and new therapeutic approaches. Gene therapy is maturing into a viable, practical method with the potential to cure a variety of human illnesses. Some nucleic-acid-based drugs are now available for controlling the progression of genetic diseases by inhibiting gene expression or the activity of their gene products. New therapeutic strategies employ a wide range of molecular tools such as bacterial plasmids containing transgenic inserts, RNA interference and aptamers. A nucleic-acid based constitution confers a lower immunogenic potential and as result of the high stringency selection of large molecular variety, these drugs have high affinity and selectivity for their targets. However, nucleic acids have poor biostability thus requiring chemical modifications and delivery systems to maintain their activity and ease their cellular internalization. This review discusses some of the mechanisms of action and the application of therapies based on nucleic acids such as aptamers and RNA interference as well as platforms for cellular uptake and intracellular delivery of therapeutic oligonucleotides and their trade-offs.",2007 Aug 9,"['Resende, R.R', 'Torres, H.A.M', 'Yuahasi, K.K', 'Majumder, P', 'Ulrich, H']",Drug Target Insights,,,True
549c70b7e76d19a76e4f6e51aa7fd9755a858a73,PMC,Cyclophilin and Viruses: Cyclophilin as a Cofactor for Viral Infection and Possible Anti-Viral Target,,PMC3155236,21901058,NO-CC CODE,"Cyclophilin (CyP) is a peptidyl prolyl cis/trans isomerase, catalyzing the cis-trans isomerization of proline residues in proteins. CyP plays key roles in several different aspects of cellular physiology including the immune response, transcription, mitochondrial function, cell death, and chemotaxis. In addition to these cellular events, a number of reports demonstrated that CyP plays a critical role in the life cycle of viruses, especially human immunodeficiency virus (HIV) and hepatitis C virus (HCV). These two viruses are significant causes of morbidity and mortality worldwide, but current therapies are often insufficient. CyP may provide a novel therapeutic target for the management and/or cure of these diseases, in particular HCV.",2007 Feb 5,"['Watashi, Koichi', 'Shimotohno, Kunitada']",Drug Target Insights,,,True
f3042820ac417ec01ca0e15a4232e24b8d78ba74,PMC,"Targeting Human Immunodeficiency Virus Type 1 Assembly, Maturation and Budding",,PMC3155237,21901072,NO-CC CODE,"The targets for licensed drugs used for the treatment of human immunodeficiency virus type 1 (HIV-1) are confined to the viral reverse transcriptase (RT), protease (PR), and the gp41 transmembrane protein (TM). While currently approved drugs are effective in controlling HIV-1 infections, new drug targets and agents are needed due to the eventual emergence of drug resistant strains and drug toxicity. Our increased understanding of the virus life-cycle and how the virus interacts with the host cell has unveiled novel mechanisms for blocking HIV-1 replication. This review focuses on inhibitors that target the late stages of virus replication including the synthesis and trafficking of the viral polyproteins, viral assembly, maturation and budding. Novel approaches to blocking the oligomerization of viral enzymes and the interactions between viral proteins and host cell factors, including their feasibility as drug targets, are discussed.",2007 Jul 20,"['Wapling, Johanna', 'Srivastava, Seema', 'Shehu-Xhilaga, Miranda', 'Tachedjian, Gilda']",Drug Target Insights,,,True
b27597f4106492dc77eb8e3e6ae832cc5a8262be,PMC,Antigen-expressing immunostimulatory liposomes as a genetically programmable synthetic vaccine,http://dx.doi.org/10.1007/s11693-010-9066-z,PMC3159695,21949673,NO-CC CODE,"Liposomes are versatile (sub)micron-sized membrane vesicles that can be used for a variety of applications, including drug delivery and in vivo imaging but they also represent excellent models for artificial membranes or cells. Several studies have demonstrated that in vitro transcription and translation can take place inside liposomes to obtain compartmentalized production of functional proteins within the liposomes (Kita et al. in Chembiochem 9(15):2403–2410, 2008; Moritani et al.in FEBS J, 2010; Kuruma et al. in Methods Mol Biol 607:161–171, 2010; Murtas et al. in Biochem Biophys Res Commun 363(1):12–17, 2007; Sunami et al. in Anal Biochem 357(1):128–136, 2006; Ishikawa et al. in FEBS Lett 576(3):387–390, 2004; Oberholzer et al. in Biochem Biophys Res Commun 261(2):238–241, 1999). Such a minimal artificial cell-based model is ideal for synthetic biology based applications. In this study, we propose the use of liposomes as artificial microbes for vaccination. These artificial microbes can be genetically programmed to produce specific antigens at will. To show proof-of-concept for this artificial cell-based platform, a bacterial in vitro transcription and translation system together with a gene construct encoding the model antigen β-galactosidase were entrapped inside multilamellar liposomes. Vaccination studies in mice showed that such antigen-expressing immunostimulatory liposomes (AnExILs) elicited higher specific humoral immune responses against the produced antigen (β-galactosidase) than control vaccines (i.e. AnExILs without genetic input, liposomal β-galactosidase or pDNA encoding β-galactosidase). In conclusion, AnExILs present a new platform for DNA-based vaccines which combines antigen production, adjuvanticity and delivery in one system and which offer several advantages over existing vaccine formulations.",2011 Jun 26,"['Amidi, Maryam', 'de Raad, Markus', 'Crommelin, Daan J. A.', 'Hennink, Wim E.', 'Mastrobattista, Enrico']",Syst Synth Biol,,,True
4a25649bbc72d2ef0e57a19221b21c486271bcfd,PMC,Amplification of Emerging Viruses in a Bat Colony,http://dx.doi.org/10.3201/eid1703.100526,PMC3165994,21392436,NO-CC CODE,"Bats host noteworthy viral pathogens, including coronaviruses, astroviruses, and adenoviruses. Knowledge on the ecology of reservoir-borne viruses is critical for preventive approaches against zoonotic epidemics. We studied a maternity colony of Myotis myotis bats in the attic of a private house in a suburban neighborhood in Rhineland-Palatinate, Germany, during 2008, 2009, and 2010. One coronavirus, 6 astroviruses, and 1 novel adenovirus were identified and monitored quantitatively. Strong and specific amplification of RNA viruses, but not of DNA viruses, occurred during colony formation and after parturition. The breeding success of the colony was significantly better in 2010 than in 2008, in spite of stronger amplification of coronaviruses and astroviruses in 2010, suggesting that these viruses had little pathogenic influence on bats. However, the general correlation of virus and bat population dynamics suggests that bats control infections similar to other mammals and that they may well experience epidemics of viruses under certain circumstances.",2011 Mar,"['Drexler, Jan Felix', 'Corman, Victor Max', 'Wegner, Tom', 'Tateno, Adriana Fumie', 'Zerbinati, Rodrigo Melim', 'Gloza-Rausch, Florian', 'Seebens, Antje', 'Müller, Marcel A.', 'Drosten, Christian']",Emerg Infect Dis,,,True
2111f7e8255fbbc35aa48c3cee385c2c3665a727,PMC,"Monitoring and Characterization of Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus, Japan, 2009–2010",http://dx.doi.org/10.3201/eid1703.101188,PMC3166015,21392439,NO-CC CODE,"To monitor and characterize oseltamivir-resistant (OR) pandemic (H1N1) 2009 virus with the H275Y mutation, we analyzed 4,307 clinical specimens from Japan by neuraminidase (NA) sequencing or inhibition assay; 61 OR pandemic (H1N1) 2009 viruses were detected. NA inhibition assay and M2 sequencing indicated that OR pandemic (H1N1) 2009 virus was resistant to M2 inhibitors, but sensitive to zanamivir. Full-genome sequencing showed OR and oseltamivir-sensitive (OS) viruses had high sequence similarity, indicating that domestic OR virus was derived from OS pandemic (H1N1) 2009 virus. Hemagglutination inhibition test demonstrated that OR and OS pandemic (H1N1) 2009 viruses were antigenically similar to the A/California/7/2009 vaccine strain. Of 61 case-patients with OR viruses, 45 received oseltamivir as treatment, and 10 received it as prophylaxis, which suggests that most cases emerged sporadically from OS pandemic (H1N1) 2009, due to selective pressure. No evidence of sustained spread of OR pandemic (H1N1) 2009 was found in Japan; however, 2 suspected incidents of human-to-human transmission were reported.",2011 Mar,"['Ujike, Makoto', 'Ejima, Miho', 'Anraku, Akane', 'Shimabukuro, Kozue', 'Obuchi, Masatsugu', 'Kishida, Noriko', 'Hong, Xu', 'Takashita, Emi', 'Fujisaki, Seiichiro', 'Yamashita, Kazuyo', 'Horikawa, Hiroshi', 'Kato, Yumiko', 'Oguchi, Akio', 'Fujita, Nobuyuki', 'Tashiro, Masato', 'Odagiri, Takato', None]",Emerg Infect Dis,,,True
cfe0fc219225651d68cd409b66bfe522f6482403,PMC,"Tuberculosis among Foreign-born Persons, Singapore, 2000–2009",http://dx.doi.org/10.3201/eid1703.101615,PMC3166031,21392448,NO-CC CODE,We determined the proportion of foreign-born persons with tuberculosis (TB) in Singapore. This proportion increased from 25.5% in 2004 to 37.6% in 2009. Unskilled workers from countries with high incidences of TB accounted for the highest number of and greatest increase in foreign-born TB case-patients.,2011 Mar,"['Win, Khin Mar Kyi', 'Chee, Cynthia B.E.', 'Shen, Liang', 'Wang, Yee T.', 'Cutter, Jeffery']",Emerg Infect Dis,,,True
a03cd1ddfd40e68547016fef7e8442d123156870,PMC,Syphilis in China: the great comeback,http://dx.doi.org/10.3134/ehtj.08.006,PMC3167587,22460215,NO-CC CODE,"China is currently witnessing a major resurgence of syphilis from the elimination of the disease in the 1960s to 5.3 per 100,000 people incidence in 2000–2005. The reasons for the elimination and subsequent resurgence of syphilis in China lie at the heart of much public health debate, highlighting both the relationship between politics and public health, and the role of government in controlling disease. Were the Draconian measures to control syphilis during the early Mao years a price worth paying for the effective control? Is the recent resurgence of syphilis an inevitable consequence of economic development and greater freedom for the individual, which will ultimately lead to better health for the majority of the population? Could tougher control measures such as those of the early Mao years be re-introduced in the current social and economic climate in China? In this review, we briefly chart the history of the syphilis epidemic in China, its elimination in the 1960s, and its gradual resurgence in the past two decades. We explore the reasons for this resurgence, and we conclude with a discussion on the options for control.",2008 Jun 20,"['Hesketh, T', 'Ye, XJ', 'Zhu, WX']",Emerg Health Threats J,,,True
a43bb56b5b1f3c5d5f30023ce701f33d670bc5ce,PMC,Age-associated impaired plasmacytoid dendritic cell functions lead to decreased CD4 and CD8 T cell immunity,http://dx.doi.org/10.1007/s11357-010-9191-3,PMC3168606,20953722,NO-CC CODE,"Increased susceptibility to infections, particularly respiratory viral infections, is a hallmark of advancing age. The underlying mechanisms are not well understood, and there is a scarcity of information regarding the contribution of the innate immune system, which is the first line of defense against infections. In the present study, we have investigated the effect of advancing age on plasmacytoid dendritic cell (PDC) function because they are critical in generating a robust antiviral response via the secretion of interferons (IFN). Our results indicate that PDCs from the aged are impaired in their capacity to secrete IFN-I in response to influenza virus and CPG stimulation. Additionally, we observed a severe reduction in the production of IFN-III, which plays an important role in defense against viral infections at respiratory mucosal surfaces. This reduction in IFN-I and IFN-III were a result of age-associated impaired phosphorylation of transcription factor, IRF-7. Furthermore, aged PDCs were observed to be impaired in their capacity to induce perforin and granzyme in CD8 T cells. Comparison of the antigen-presenting capacity of aged PDC with young PDC revealed that PDCs from aged subjects display reduced capacity to induce proliferation and IFN-gamma secretion in CD4 and CD8 T cells as compared with PDCs from young subjects. In summary, our study demonstrates that advancing age has a profound effect on PDC function at multiple levels and may therefore, be responsible for the increased susceptibility to infections in the elderly.",2011 Sep 16,"['Sridharan, Aishwarya', 'Esposo, Marc', 'Kaushal, Khushboo', 'Tay, Jia', 'Osann, Kathyrn', 'Agrawal, Sudhanshu', 'Gupta, Sudhir', 'Agrawal, Anshu']",Age (Dordr),,,True
3ee377ece8b8a1fb6a4468d39d410f0f33042051,PMC,Is respiratory viral infection really an important trigger of asthma exacerbations in children?,http://dx.doi.org/10.1007/s00431-011-1446-1,PMC3175036,21448631,NO-CC CODE,"We performed a prospective cohort study from September 2003 to December 2004 to delineate attributing the effect of different respiratory viral infections including newly discovered ones to asthma exacerbations in children in Hong Kong. One hundred and fourteen children aged 6–14 years with chronic stable asthma and on regular inhaled steroid were monitored for respiratory symptoms over a full calendar year from recruitment. They would attend the study clinic if peak expiratory flow rate decreased to below 80% of their baselines, if they met a predefined symptom score, or if parents subjectively felt them developing a cold. Virological diagnosis using virus culture, antigen detection, and polymerase chain reaction methods on nasal swab specimens would be attempted for all these visits irrespective of triggers. Physician diagnosed outcome of each episode was documented. Three hundred and five episodes of respiratory illnesses were captured in the cohort. Nasal specimens were available in 166 episodes, 92 of which were diagnosed as asthma exacerbations, and 74 non-asthma related episodes. Respiratory viruses were detected in 61 of 166 episodes (36.7%). There was no significant difference in virus detection rate between asthma exacerbations (32 out of 97 episodes, 34.8%) and non-asthma respiratory illnesses (29 out of 79 episodes, 39.2%). Although newly discovered respiratory viruses were identified in these episodes, rhinovirus was the commonest organism associated with both asthma exacerbations and non-asthma related episodes. Plausible explanations for much lower virus detection rate than previously reported include improved personal hygiene and precautionary measures taken during respiratory tract infections in the immediate post-severe acute respiratory syndrome period together with a significant contribution of other adverse factors like environmental air pollution. We conclude that not all viral infections in children with asthma lead to an asthma exacerbation and the attributing effect of different triggers of asthma exacerbations in children vary across different time periods and across different localities.",2011 Oct 30,"['Lee, So-lun', 'Chiu, Shui-seng Susan', 'Malik, Peiris Joseph S.', 'Chan, Kwok-hung', 'Wong, Hing-sang Wilfred', 'Lau, Yu-lung']",Eur J Pediatr,,,True
bfebea5629eb128672f452ba095d7b2057401410,PMC,Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children,http://dx.doi.org/10.1111/j.1750-2659.2011.00265.x,PMC3175338,21668660,NO-CC CODE,"Please cite this paper as: Martin et al. (2012) Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children. Influenza and Other Respiratory Viruses 6(1), 71–77. Background  Molecular testing for viral pathogens has resulted in increasing detection of multiple viruses in respiratory secretions of ill children. The clinical impact of multiple virus infections on clinical presentation and outcome is unclear. Objectives  To compare clinical characteristics and viral load between children with multiple virus versus single virus illnesses. Patients/methods  Eight hundred and ninety‐three residual nasal wash samples from children treated for respiratory illness at Children’s Hospital, Seattle, from September 2003 to September 2004 were evaluated by quantitative PCR for respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (Flu), parainfluenza, adenoviruses, and coronaviruses (CoV). Illness severity and patient characteristics were abstracted from medical charts. Results  Coinfections were identified in 103 (18%) of 566 virus‐positive samples. Adenovirus was most commonly detected in coinfections (52%), followed by CoV (50%). Illnesses with a single virus had increased risk of oxygen requirement (P = 0·02), extended hospital stays (P = 0·002), and admissions to the inpatient (P = 0·02) or intensive care units (P = 0·04). For Adv and PIV‐1, multiple virus illnesses had a significantly lower viral load (log(10) copies/ml) than single virus illnesses (4·2 versus 5·6, P = 0·007 and 4·2 versus 6·9, P < 0·001, respectively). RSV, Flu‐A, PIV‐3, and hMPV viral loads were consistently high whether or not another virus was detected. Conclusions  Illnesses with multiple virus detections were correlated with less severe disease. The relationship between viral load and multiple virus infections was virus specific, and this may serve as a way to differentiate viruses in multiple virus infections.",2012 Jan 31,"['Martin, Emily T.', 'Kuypers, Jane', 'Wald, Anna', 'Englund, Janet A.']",Influenza Other Respir Viruses,,,True
f74d6f598edd77d5ececd51da9d900910b21186d,PMC,Implications of Host Genetic Variation on the Risk and Prevalence of Infectious Diseases Transmitted Through the Environment,http://dx.doi.org/10.1534/genetics.110.125625,PMC3176547,21527777,NO-CC CODE,"Previous studies have shown that host genetic heterogeneity in the response to infectious challenge can affect the emergence risk and the severity of diseases transmitted through direct contact between individuals. However, there is substantial uncertainty about the degree and direction of influence owing to different definitions of genetic variation, most of which are not in line with the current understanding of the genetic architecture of disease traits. Also, the relevance of previous results for diseases transmitted through environmental sources is unclear. In this article a compartmental genetic–epidemiological model was developed to quantify the impact of host genetic diversity on epidemiological characteristics of diseases transmitted through a contaminated environment. The model was parameterized for footrot in sheep. Genetic variation was defined through continuous distributions with varying shape and degree of dispersion for different disease traits. The model predicts a strong impact of genetic heterogeneity on the disease risk and its progression and severity, as well as on observable host phenotypes, when dispersion in key epidemiological parameters is high. The impact of host variation depends on the disease trait for which variation occurs and on environmental conditions affecting pathogen survival. In particular, compared to homogeneous populations with the same average susceptibility, disease risk and severity are substantially higher in populations containing a large proportion of highly susceptible individuals, and the differences are strongest when environmental contamination is low. The implications of our results for the recording and analysis of disease data and for predicting response to selection are discussed.",2011 Jul,"['Doeschl-Wilson, Andrea B.', 'Davidson, R.', 'Conington, J.', 'Roughsedge, T.', 'Hutchings, M. R.', 'Villanueva, B.']",Genetics,,,True
8f92e63e66110b0e8c72eb9385ddfa957c404aea,PMC,Current status of multiple antigen-presenting peptide vaccine systems: Application of organic and inorganic nanoparticles,http://dx.doi.org/10.1186/1752-153X-5-48,PMC3178480,21861904,NO-CC CODE,"Many studies are currently investigating the development of safe and effective vaccines to prevent various infectious diseases. Multiple antigen-presenting peptide vaccine systems have been developed to avoid the adverse effects associated with conventional vaccines (i.e., live-attenuated, killed or inactivated pathogens), carrier proteins and cytotoxic adjuvants. Recently, two main approaches have been used to develop multiple antigen-presenting peptide vaccine systems: (1) the addition of functional components, e.g., T-cell epitopes, cell-penetrating peptides, and lipophilic moieties; and (2) synthetic approaches using size-defined nanomaterials, e.g., self-assembling peptides, non-peptidic dendrimers, and gold nanoparticles, as antigen-displaying platforms. This review summarizes the recent experimental studies directed to the development of multiple antigen-presenting peptide vaccine systems.",2011 Aug 23,"['Fujita, Yoshio', 'Taguchi, Hiroaki']",Chem Cent J,,,True
7052dc3cb4e9de110fbec8baddc369d6d53b3fba,PMC,Detection of alpha and betacoronaviruses in multiple Iberian bat species,http://dx.doi.org/10.1007/s00705-011-1057-1,PMC3181409,21766197,NO-CC CODE,"Bat coronaviruses (CoV) are putative precursors of the severe acute respiratory syndrome (SARS) CoV and other CoV that crossed the species barrier from zoonotic reservoirs into the human population. To determine the presence and distribution of CoV in Iberian bats, 576 individuals of 26 different bat species were captured in 13 locations in Spain. We report for the first time the presence of 14 coronaviruses in 9 Iberian bat species. Phylogenetic analysis of a conserved CoV genome region (RdRp gene) shows a wide diversity and distribution of alpha and betacoronavirus in Spain. Interestingly, although some of these viruses are related to other European BatCoV, or to Asian CoV, some of the viruses found in Spain cluster in new groups of α and β CoV.",2011 Oct 16,"['Falcón, Ana', 'Vázquez-Morón, Sonia', 'Casas, Inmaculada', 'Aznar, Carolina', 'Ruiz, Guillermo', 'Pozo, Francisco', 'Perez-Breña, Pilar', 'Juste, Javier', 'Ibáñez, Carlos', 'Garin, Inazio', 'Aihartza, Joxerra', 'Echevarría, Juan E.']",Arch Virol,,,True
4c9593ce46963b23b3bdb053ae80a600ed96492a,PMC,Protein Disulfide Isomerase and Host-Pathogen Interaction,http://dx.doi.org/10.1100/2011/289182,PMC3201685,22125433,NO-CC CODE,"Reactive oxygen species (ROS) production by immunological cells is known to cause damage to pathogens. Increasing evidence accumulated in the last decade has shown, however, that ROS (and redox signals) functionally regulate different cellular pathways in the host-pathogen interaction. These especially affect (i) pathogen entry through protein redox switches and redox modification (i.e., intra- and interdisulfide and cysteine oxidation) and (ii) phagocytic ROS production via Nox family NADPH oxidase enzyme and the control of phagolysosome function with key implications for antigen processing. The protein disulfide isomerase (PDI) family of redox chaperones is closely involved in both processes and is also implicated in protein unfolding and trafficking across the endoplasmic reticulum (ER) and towards the cytosol, a thiol-based redox locus for antigen processing. Here, we summarise examples of the cellular association of host PDI with different pathogens and explore the possible roles of pathogen PDIs in infection. A better understanding of these complex regulatory steps will provide insightful information on the redox role and coevolutional biological process, and assist the development of more specific therapeutic strategies in pathogen-mediated infections.",2011 Oct 11,"['Stolf, Beatriz S.', 'Smyrnias, Ioannis', 'Lopes, Lucia R.', 'Vendramin, Alcione', 'Goto, Hiro', 'Laurindo, Francisco R. M.', 'Shah, Ajay M.', 'Santos, Celio X. C.']",ScientificWorldJournal,,,True
185a01541eeba3c18e5c68ee961fdabd6069564e,PMC,Improved Immunological Tolerance Following Combination Therapy with CTLA-4/Ig and AAV-Mediated PD-L1/2 Muscle Gene Transfer,http://dx.doi.org/10.3389/fmicb.2011.00199,PMC3202221,22046170,NO-CC CODE,"Initially thought as being non-immunogenic, recombinant AAVs have emerged as efficient vector candidates for treating monogenic diseases. It is now clear however that they induce potent immune responses against transgene products which can lead to destruction of transduced cells. Therefore, developing strategies to circumvent these immune responses and facilitate long-term expression of transgenic therapeutic proteins is a main challenge in gene therapy. We evaluated herein a strategy to inhibit the undesirable immune activation that follows muscle gene transfer by administration of CTLA-4/Ig to block the costimulatory signals required early during immune priming and by using gene transfer of PD-1 ligands to inhibit T cell functions at the tissue sites. We provide the proof of principle that this combination immunoregulatory therapy targeting two non-redundant checkpoints of the immune response, i.e., priming and effector functions, can improve persistence of transduced cells in experimental settings where cytotoxic T cells escape initial blockade. Therefore, CTLA-4/Ig plus PD-L1/2 combination therapy represents a candidate approach to circumvent the bottleneck of immune responses directed toward transgene products.",2011 Sep 29,"['Adriouch, Sahil', 'Franck, Emilie', 'Drouot, Laurent', 'Bonneau, Carole', 'Jolinon, Nelly', 'Salvetti, Anna', 'Boyer, Olivier']",Front Microbiol,,,True
373474bd0d2c88363e7fad85fa0ca0863687a791,PMC,"Completeness of Communicable Disease Reporting, North Carolina, USA, 1995–1997 and 2000–2006",http://dx.doi.org/10.3201/eid1701.100660,PMC3204630,21192850,NO-CC CODE,"Despite widespread use of communicable disease surveillance data to inform public health intervention and control measures, the reporting completeness of the notifiable disease surveillance system remains incompletely assessed. Therefore, we conducted a comprehensive study of reporting completeness with an analysis of 53 diseases reported by 8 health care systems across North Carolina, USA, during 1995–1997 and 2000–2006. All patients who were assigned an International Classification of Diseases, 9th Revision, Clinical Modification, diagnosis code for a state-required reportable communicable disease were matched to surveillance records. We used logistic regression techniques to estimate reporting completeness by disease, year, and health care system. The completeness of reporting varied among the health care systems from 2% to 30% and improved over time. Disease-specific reporting completeness proportions ranged from 0% to 82%, but were generally low even for diseases with great public health importance and opportunity for interventions.",2011 Jan,"['Sickbert-Bennett, Emily E.', 'Weber, David J.', 'Poole, Charles', 'MacDonald, Pia D.M.', 'Maillard, Jean-Marie']",Emerg Infect Dis,,,True
28cd0535d235f1323e6da447732751774f207ce1,PMC,Usefulness of Published PCR Primers in Detecting Human Rhinovirus Infection,http://dx.doi.org/10.3201/eid1702.101123,PMC3204776,21291610,NO-CC CODE,"We conducted a preliminary comparison of the relative sensitivity of a cross-section of published human rhinovirus (HRV)–specific PCR primer pairs, varying the oligonucleotides and annealing temperature. None of the pairs could detect all HRVs in 2 panels of genotyped clinical specimens; >1 PCR is required for accurate description of HRV epidemiology.",2011 Feb,"['Faux, Cassandra E.', 'Arden, Katherine E.', 'Lambert, Stephen B.', 'Nissen, Michael D.', 'Nolan, Terry M.', 'Chang, Anne B.', 'Sloots, Theo P.', 'Mackay, Ian M.']",Emerg Infect Dis,,,True
b32b26b8d44120d0daaa6fa57f5fd73234085837,PMC,Applications of the Phytomedicine Echinacea purpurea (Purple Coneflower) in Infectious Diseases,http://dx.doi.org/10.1155/2012/769896,PMC3205674,22131823,NO-CC CODE,"Extracts of Echinacea purpurea (EP, purple coneflower) have been used traditionally in North America for the treatment of various types of infections and wounds, and they have become very popular herbal medicines globally. Recent studies have revealed that certain standardized preparations contain potent and selective antiviral and antimicrobial activities. In addition, they display multiple immune-modulatory activities, comprising stimulation of certain immune functions such as phagocytic activity of macrophages and suppression of the proinflammatory responses of epithelial cells to viruses and bacteria, which are manifested as alterations in secretion of various cytokines and chemokines. These immune modulations result from upregulation or downregulation of the relevant genes and their transcription factors. All these bioactivities can be demonstrated at noncytotoxic concentrations of extract and appear to be due to multiple components rather than the individual chemical compounds that characterize Echinacea extracts. Potential applications of the bioactive extracts may go beyond their traditional uses.",2012 Oct 26,"Hudson, James B.",J Biomed Biotechnol,,,True
166b70bab11b13953f7a074daa76bbe53d7300b7,PMC,Immune Responses to rAAV6: The Influence of Canine Parvovirus Vaccination and Neonatal Administration of Viral Vector,http://dx.doi.org/10.3389/fmicb.2011.00220,PMC3207220,22065964,NO-CC CODE,"Recombinant adeno-associated viral (rAAV) vectors promote long-term gene transfer in many animal species. Significant effort has focused on the evaluation of rAAV delivery and the immune response in both murine and canine models of neuromuscular disease. However, canines provided for research purposes are routinely vaccinated against canine parvovirus (CPV). rAAV and CPV possess significant homology and are both parvoviruses. Thus, any immune response generated to CPV vaccination has the potential to cross-react with rAAV vectors. In this study, we investigated the immune response to rAAV6 delivery in a cohort of CPV-vaccinated canines and evaluated multiple vaccination regimens in a mouse model of CPV-vaccination. We show that CPV-vaccination stimulates production of neutralizing antibodies with minimal cross-reactivity to rAAV6. In addition, no significant differences were observed in the magnitude of the rAAV6-directed immune response between CPV-vaccinated animals and controls. Moreover, CPV-vaccination did not inhibit rAAV6-mediated transduction. We also evaluated the immune response to early rAAV6-vaccination in neonatal mice. The influence of maternal hormones and cytokines leads to a relatively permissive state in the neonate. We hypothesized that immaturity of the immune system would permit induction of tolerance to rAAV6 when delivered during the neonatal period. Mice were vaccinated with rAAV6 at 1 or 5 days of age, and subsequently challenged with rAAV6 exposure during adulthood via two sequential IM injections, 1 month apart. All vaccinated animals generated a significant neutralizing antibody response to rAAV6-vaccination that was enhanced following IM injection in adulthood. Taken together, these data demonstrate that the immune response raised against rAAV6 is distinct from that which is elicited by the standard parvoviral vaccines and is sufficient to prevent stable tolerization in neonatal mice.",2011 Nov 3,"['Arnett, Andrea L. H.', 'Garikipati, Dilip', 'Wang, Zejing', 'Tapscott, Stephen', 'Chamberlain, Jeffrey S.']",Front Microbiol,,,True
3cdfc63c3790d0bc50c45fe33b2b7ca304641a5d,PMC,Interfering Waves of Adaptation Promote Spatial Mixing,http://dx.doi.org/10.1534/genetics.111.130112,PMC3213383,21900264,NO-CC CODE,"A fundamental problem of asexual adaptation is that beneficial substitutions are not efficiently accumulated in large populations: Beneficial mutations often go extinct because they compete with one another in going to fixation. It has been argued that such clonal interference may have led to the evolution of sex and recombination in well-mixed populations. Here, we study clonal interference, and mechanisms of its mitigation, in an evolutionary model of spatially structured populations with uniform selection pressure. Clonal interference is much more prevalent with spatial structure than without, due to the slow wave-like spread of beneficial mutations through space. We find that the adaptation speed of asexuals saturates when the linear habitat size exceeds a characteristic interference length, which becomes shorter with smaller migration and larger mutation rate. The limiting speed is proportional to μ(1/2) and μ(1/3) in linear and planar habitats, respectively, where the mutational supply μ is the product of mutation rate and local population density. This scaling and the existence of a speed limit should be amenable to experimental tests as they fall far below predicted adaptation speeds for well-mixed populations (that scale as the logarithm of population size). Finally, we show that not only recombination, but also long-range migration is a highly efficient mechanism of relaxing clonal competition in structured populations. Our conservative estimates of the interference length predict prevalent clonal interference in microbial colonies and biofilms, so clonal competition should be a strong driver of both genetic and spatial mixing in those contexts.",2011 Nov,"['Martens, Erik A.', 'Hallatschek, Oskar']",Genetics,,,True
0d8f8313ebf345a47ae755d7f470b393a79893fe,PMC,A putative diacidic motif in the SARS-CoV ORF6 protein influences its subcellular localization and suppression of expression of co-transfected expression constructs,http://dx.doi.org/10.1186/1756-0500-4-446,PMC3219739,22026976,NO-CC CODE,"BACKGROUND: The ORF6 protein is one of the eight accessory proteins of the severe acute respiratory syndrome coronavirus (SARS-CoV). Numerous properties of ORF6 have been documented and this study focuses on two of these, namely, its ability to suppress the expression of co-transfected expression constructs and its subcellular localization to vesicular structures. RESULTS: Using a transient transfection system, ORF6's ability to suppress the expression of co-transfected expression constructs was measured in a quantitative manner. While ORF6 does not have a global effect on protein synthesis, quantitative real-time PCR revealed that it down-regulated the mRNA level of the co-transfected myc-nsp8 gene. Furthermore, alanine substitution of a diacidic cluster motif (aa53-56) in the ORF6 gene caused a reduction in the suppression of expression of co-transfected myc-nsp8 gene. Our previous study revealed that ORF6 localized to vesicular structures in SARS-CoV infected Vero E6 cells. Here, ORF6 was observed to be localized to similar vesicular structures in Vero E6 cells which have been transiently transfected with a mammalian expression plasmid encoding for untagged ORF6. ORF6 showed partial colocalization with cellular proteins CD63 and Lamp1, suggesting that the vesicular structures may be a subpopulation of endosomal/lysosomal vesicles. The alanine substitution of the diacidic cluster motif also altered the subcellular localization of the ORF6 protein, indicating a potential relationship between the subcellular localization of the ORF6 protein and its ability to suppress the expression of co-transfected expression constructs. CONCLUSIONS: By combining quantitative real-time PCR and transient transfection system, a simple and safe method is established to measure ORF6's ability to suppress the expression of co-transfected myc-nsp8. In addition, immunofluorescence analysis revealed that the subcellular localization of ORF6 when expressed on its own is similar to that observed in SARS-CoV infected cells. Through the use of these two assays, a putative diacidic motif in the ORF6 protein was found to influence its subcellular localization and ability to suppress the expression of co-transfected expression constructs.",2011 Oct 25,"['Gunalan, Vithiagaran', 'Mirazimi, Ali', 'Tan, Yee-Joo']",BMC Res Notes,,,True
7f0b1ae991e40333c7bd010c6a621322f09ac888,PMC,Bacterial contamination of platelet concentrates: pathogen detection and inactivation methods,http://dx.doi.org/10.4081/hr.2009.e5,PMC3222246,,NO-CC CODE,"Whereas the reduction of transfusion related viral transmission has been a priority during the last decade, bacterial infection transmitted by transfusion still remains associated to a high morbidity and mortality, and constitutes the most frequent infectious risk of transfusion. This problem especially concerns platelet concentrates because of their favorable bacterial growth conditions. This review gives an overview of platelet transfusion-related bacterial contamination as well as on the different strategies to reduce this problem by using either bacterial detection or inactivation methods.",2009 Apr 16,"['Védy, Dana', 'Robert, Daniel', 'Gasparini, Danielle', 'Canellini, Giorgia', 'Waldvogel, Sophie', 'Tissot, Jean-Daniel']",Hematol Rev,,,True
c160b476d630126321658e6cd0d00276af4875d1,PMC,Apoptosis induced in vivo by new type gosling viral enteritis virus,http://dx.doi.org/10.4142/jvs.2011.12.4.333,PMC3232392,22122899,NO-CC CODE,"In this study, apoptosis was induced by new type gosling viral enteritis virus (NGVEV) in experimentally infected goslings is reported in detail for the first time. After 3-day-old goslings were orally inoculated with a NGVEV-CN strain suspension, the time course of NGVEV effects on apoptotic morphological changes of the internal tissues was evaluated. These changes were observed by histological analysis with light microscopy and ultrastructural analysis with transmission electron microscopy. DNA fragmentation was assessed with a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay and DNA ladder analysis. A series of characteristic apoptotic morphological changes including chromatin condensation and margination, cytoplasmic shrinkage, plasma membrane blebbing, and formation of apoptotic bodies were noted. Apoptosis was readily observed in the lymphoid and gastrointestinal organs, and sporadically occurred in other organs after 3 days post-infection (PI). The presence and quantity of TUNEL-positive cells increased with infection time until 9 days PI. DNA extracted from the NGVEV-infected gosling cells displayed characteristic 180~200 bp ladders. Apoptotic cells were ubiquitously distributed, especially among lymphocytes, macrophages, monocytes, and epithelial and intestinal cells. Necrosis was subsequently detected during the late NGVEV-infection phase, which was characterized by cell swelling, plasma membrane collapse, and rapidly lysis. Our results suggested that apoptosis may play an important role in the pathogenesis of NGVE disease.",2011 Dec 30,"['Chen, Shun', 'Cheng, Anchun', 'Wang, Mingshu', 'Zhu, Dekang', 'Jia, Renyong', 'Luo, Qihui', 'Cui, Hengmin', 'Zhou, Yi', 'Wang, Yin', 'Xu, Zhiwen', 'Chen, Zhengli', 'Chen, Xiaoyue', 'Wang, Xiaoyu']",J Vet Sci,,,True
f87281bef799be6149320996f90bccc2194d7652,PMC,Interference of H-bonding and substituent effects in nitro- and hydroxy-substituted salicylaldehydes,http://dx.doi.org/10.1007/s00894-011-1044-1,PMC3249548,21523547,NO-CC CODE,"Two intramolecular interactions, i.e., (1) hydrogen bond and (2) substituent effect, were analyzed and compared. For this purpose, the geometry of 4- and 5-X-substituted salicylaldehyde derivatives (X = NO(2), H or OH) was optimized by means of B3LYP/6-311 + G(d,p) and MP2/aug-cc-pVDZ methods. The results obtained allowed us to show that substituents (NO(2) or OH) in the para or meta position with respect to either OH or CHO in H-bonded systems interact more strongly than in the case of di-substituted species: 4- and 3-nitrophenol or 4- and 3-hydroxybenzaldehyde by ∼31%. The substituent effect due to the intramolecular charge transfer from the para-counter substituent (NO(2)) to the proton-donating group (OH) is ∼35% greater than for the interaction of para-OH with the proton-accepting group (CHO). The total energy of H-bonding for salicylaldehyde, and its derivatives, is composed of two contributions: ∼80% from the energy of H-bond formation and ∼20% from the energy associated with reorganization of the electron structure of the systems in question. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00894-011-1044-1) contains supplementary material, which is available to authorized users.",2012 Jan 27,"['Jezierska-Mazzarello, Aneta', 'Szatyłowicz, Halina', 'Krygowski, Tadeusz Marek']",J Mol Model,,,True
87d1712d269ca273a4496d43b91c472df46bbd38,PMC,Interference of H-bonding and substituent effects in nitro- and hydroxy-substituted salicylaldehydes,http://dx.doi.org/10.1007/s00894-011-1044-1,PMC3249548,21523547,NO-CC CODE,"Two intramolecular interactions, i.e., (1) hydrogen bond and (2) substituent effect, were analyzed and compared. For this purpose, the geometry of 4- and 5-X-substituted salicylaldehyde derivatives (X = NO(2), H or OH) was optimized by means of B3LYP/6-311 + G(d,p) and MP2/aug-cc-pVDZ methods. The results obtained allowed us to show that substituents (NO(2) or OH) in the para or meta position with respect to either OH or CHO in H-bonded systems interact more strongly than in the case of di-substituted species: 4- and 3-nitrophenol or 4- and 3-hydroxybenzaldehyde by ∼31%. The substituent effect due to the intramolecular charge transfer from the para-counter substituent (NO(2)) to the proton-donating group (OH) is ∼35% greater than for the interaction of para-OH with the proton-accepting group (CHO). The total energy of H-bonding for salicylaldehyde, and its derivatives, is composed of two contributions: ∼80% from the energy of H-bond formation and ∼20% from the energy associated with reorganization of the electron structure of the systems in question. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00894-011-1044-1) contains supplementary material, which is available to authorized users.",2012 Jan 27,"['Jezierska-Mazzarello, Aneta', 'Szatyłowicz, Halina', 'Krygowski, Tadeusz Marek']",J Mol Model,,,True
b44c16070a980ad9258249edfc99db4f17149d99,PMC,ColorPhylo: A Color Code to Accurately Display Taxonomic Classifications,http://dx.doi.org/10.4137/EBO.S7565,PMC3255521,22253532,NO-CC CODE,"Color may be very useful to visualise complex data. As far as taxonomy is concerned, color may help observing various species’ characteristics in correlation with classification. However, choosing the number of subclasses to display is often a complex task: on the one hand, assigning a limited number of colors to taxa of interest hides the structure imbedded in the subtrees of the taxonomy; on the other hand, differentiating a high number of taxa by giving them specific colors, without considering the underlying taxonomy, may lead to unreadable results since relationships between displayed taxa would not be supported by the color code. In the present paper, an automatic color coding scheme is proposed to visualise the levels of taxonomic relationships displayed as overlay on any kind of data plot. To achieve this goal, a dimensionality reduction method allows displaying taxonomic “distances” onto a Euclidean two-dimensional space. The resulting map is projected onto a 2D color space (the Hue, Saturation, Brightness colorimetric space with brightness set to 1). Proximity in the taxonomic classification corresponds to proximity on the map and is therefore materialised by color proximity. As a result, each species is related to a color code showing its position in the taxonomic tree. The so called ColorPhylo displays taxonomic relationships intuitively and can be combined with any biological result. A Matlab version of ColorPhylo is available at http://sy.lespi.free.fr/ColorPhylo-homepage.html. Meanwhile, an ad-hoc distance in case of taxonomy with unknown edge lengths is proposed.",2011 Nov 13,"['Lespinats, Sylvain', 'Fertil, Bernard']",Evol Bioinform Online,,,True
d45eca08453374762035363feb89e80b414f6105,PMC,The crazy-paving pattern: a radiological-pathological correlation,http://dx.doi.org/10.1007/s13244-010-0060-5,PMC3259383,22347941,NO-CC CODE,"The crazy-paving pattern is a linear pattern superimposed on a background of ground-glass opacity, resembling irregularly shaped paving stones. The crazy-paving pattern is initially described as the pathognomonic sign of alveolar proteinosis. Nowadays this pattern is a common finding on high-resolution CT imaging, and can be seen in a number of acute and chronic diseases. The purpose of this paper is to illustrate different diseases that cause this crazy-paving pattern and to correlate the radiological findings from computed tomography with the histopathological findings.",2011 Jan 9,"['De Wever, Walter', 'Meersschaert, Joke', 'Coolen, Johan', 'Verbeken, Eric', 'Verschakelen, Johny A']",Insights Imaging,,,True
22e62964e71141a66a131787be751d6787efcdbf,PMC,Quantitative trace analysis of a broad range of antiviral drugs in poultry muscle using column-switch liquid chromatography coupled to tandem mass spectrometry,http://dx.doi.org/10.1007/s00216-011-5581-3,PMC3262966,22173207,NO-CC CODE,"A liquid chromatography–tandem mass spectrometry method for the analysis of seven antiviral drugs, zanamivir, ribavirin, oseltamivir, oseltamivir carboxylate, amantadine, rimantadine and arbidol, in poultry muscle is reported. The antiviral drugs were extracted from the homogenized poultry muscle sample using methanol. The extract was purified using tandem solid-phase extraction combining a cation exchange cartridge and a phenylboronic acid cartridge. To prevent excessive matrix effects, the analytes were separated from the matrix constituents using a column-switch liquid chromatography system combining a reversed-phase and a Hypercarb analytical column. Detection was carried out using tandem mass spectrometry. The method was fully validated according to 2002/657/EC [1] and proved to be adequate for quantification and confirmation of zanamivir and ribavirin at 10 μg kg(−1), oseltamivir, oseltamivir carboxylate, amantadine and rimantadine at levels below 1.0 μg kg(−1) and for qualitative confirmatory analysis of arbidol at levels below 1 μg kg(−1). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00216-011-5581-3) contains supplementary material, which is available to authorized users.",2012 Feb 16,"['Berendsen, Bjorn J. A.', 'Wegh, Robin S.', 'Essers, Martien L.', 'Stolker, Alida A. M.', 'Weigel, Stefan']",Anal Bioanal Chem,,,False
f2ea312712d4e9fbe371d2ccb5cfdca0c6348c53,PMC,Quantitative trace analysis of a broad range of antiviral drugs in poultry muscle using column-switch liquid chromatography coupled to tandem mass spectrometry,http://dx.doi.org/10.1007/s00216-011-5581-3,PMC3262966,22173207,NO-CC CODE,"A liquid chromatography–tandem mass spectrometry method for the analysis of seven antiviral drugs, zanamivir, ribavirin, oseltamivir, oseltamivir carboxylate, amantadine, rimantadine and arbidol, in poultry muscle is reported. The antiviral drugs were extracted from the homogenized poultry muscle sample using methanol. The extract was purified using tandem solid-phase extraction combining a cation exchange cartridge and a phenylboronic acid cartridge. To prevent excessive matrix effects, the analytes were separated from the matrix constituents using a column-switch liquid chromatography system combining a reversed-phase and a Hypercarb analytical column. Detection was carried out using tandem mass spectrometry. The method was fully validated according to 2002/657/EC [1] and proved to be adequate for quantification and confirmation of zanamivir and ribavirin at 10 μg kg(−1), oseltamivir, oseltamivir carboxylate, amantadine and rimantadine at levels below 1.0 μg kg(−1) and for qualitative confirmatory analysis of arbidol at levels below 1 μg kg(−1). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00216-011-5581-3) contains supplementary material, which is available to authorized users.",2012 Feb 16,"['Berendsen, Bjorn J. A.', 'Wegh, Robin S.', 'Essers, Martien L.', 'Stolker, Alida A. M.', 'Weigel, Stefan']",Anal Bioanal Chem,,,True
14d04f36cb13550aa7769b61a079fa54031a21eb,PMC,Public health measures during an anticipated influenza pandemic: Factors influencing willingness to comply,,PMC3270909,22312204,NO-CC CODE,"This research assessed factors associated with willingness to comply with vaccination, isolation, and face mask wearing during an anticipated influenza pandemic. Data were collected from 2081 adults (16+) using a module of questions incorporated into the NSW Health Adult Population Health Survey. High levels of willingness to comply were reported with 73% either very or extremely willing to receive vaccination, 67% willing to isolate themselves, 58% willing to wear a face mask, and 48% willing to comply with all three behaviors. Further analysis indicated concern for self and family and higher levels of education were associated with high levels of willingness to comply. Younger people (16–24) were the least willing to comply; especially with wearing a face mask. Those with children reported higher levels of willingness to receive vaccination, and respondents who speak a language other than English at home were less willing to isolate themselves or comply with all behaviors. These findings provide a baseline measure of anticipated public compliance with key public health behaviors in the event of an influenza pandemic in the Australian population, and help to identify groups that may be more resistant to individual measures and may require additional attention in terms of risk communication strategies or health education.",2009 Jan 29,"['Taylor, Melanie', 'Raphael, Beverley', 'Barr, Margo', 'Agho, Kingsley', 'Stevens, Garry', 'Jorm, Louisa']",Risk Manag Healthc Policy,,,True
6a07f0ba055d2d843908ad7683bc36c3f46e1550,PMC,Systematic Review of Economic Evaluations of Preparedness Strategies and Interventions against Influenza Pandemics,http://dx.doi.org/10.1371/journal.pone.0030333,PMC3290611,22393352,NO-CC CODE,"BACKGROUND: Although public health guidelines have implications for resource allocation, these issues were not explicitly considered in previous WHO pandemic preparedness and response guidance. In order to ensure a thorough and informed revision of this guidance following the H1N1 2009 pandemic, a systematic review of published and unpublished economic evaluations of preparedness strategies and interventions against influenza pandemics was conducted. METHODS: The search was performed in September 2011 using 10 electronic databases, 2 internet search engines, reference list screening, cited reference searching, and direct communication with relevant authors. Full and partial economic evaluations considering both costs and outcomes were included. Conversely, reviews, editorials, and studies on economic impact or complications were excluded. Studies were selected by 2 independent reviewers. RESULTS: 44 studies were included. Although most complied with the cost effectiveness guidelines, the quality of evidence was limited. However, the data sources used were of higher quality in economic evaluations conducted after the 2009 H1N1 pandemic. Vaccination and drug regimens were varied. Pharmaceutical plus non-pharmaceutical interventions are relatively cost effective in comparison to vaccines and/or antivirals alone. Pharmaceutical interventions vary from cost saving to high cost effectiveness ratios. According to ceiling thresholds (Gross National Income per capita), the reduction of non-essential contacts and the use of pharmaceutical prophylaxis plus the closure of schools are amongst the cost effective strategies for all countries. However, quarantine for household contacts is not cost effective even for low and middle income countries. CONCLUSION: The available evidence is generally inconclusive regarding the cost effectiveness of preparedness strategies and interventions against influenza pandemics. Studies on their effectiveness and cost effectiveness should be readily implemented in forthcoming events that also involve the developing world. Guidelines for assessing the impact of disease and interventions should be drawn up to facilitate these studies.",2012 Feb 29,"['Pérez Velasco, Román', 'Praditsitthikorn, Naiyana', 'Wichmann, Kamonthip', 'Mohara, Adun', 'Kotirum, Surachai', 'Tantivess, Sripen', 'Vallenas, Constanza', 'Harmanci, Hande', 'Teerawattananon, Yot']",PLoS One,,,True
7affb8951346d72458b9aa05be31531d43695add,PMC,"Public Understanding of Pandemic Influenza, United Kingdom",http://dx.doi.org/10.3201/eid1210.060208,PMC3290942,17176595,NO-CC CODE,,2006 Oct,"['Gupta, Ravindra K.', 'Toby, Martina', 'Bandopadhyay, Gagori', 'Cooke, Mary', 'Gelb, David', 'Nguyen-Van-Tam, Jonathan S.']",Emerg Infect Dis,,,True
55ddef381063d2056a4f4b1051a0ed3c476bc010,PMC,Severe Pneumonia and Human Bocavirus in Adult,http://dx.doi.org/10.3201/eid1210.060520,PMC3290954,17176591,NO-CC CODE,,2006 Oct,"['Kupfer, Bernd', 'Vehreschild, Jörg', 'Cornely, Oliver', 'Kaiser, Rolf', 'Plum, Gerhard', 'Viazov, Sergei', 'Franzen, Caspar', 'Tillmann, Ramona-Liza', 'Simon, Arne', 'Müller, Andreas', 'Schildgen, Oliver']",Emerg Infect Dis,,,True
d4fa60c6535f776f6350942c3636069ed04b2771,PMC,Novel Chikungunya Virus Variant in Travelers Returning from Indian Ocean Islands,http://dx.doi.org/10.3201/eid1210.060610,PMC3290960,17176562,NO-CC CODE,"Chikungunya virus (CHIKV) emerged in Indian Ocean islands in 2005 and is causing an ongoing outbreak that involves >260,000 patients, including travelers returning home from these islands. We investigated cases in 4 patients returning from Mayotte and Reunion Islands with CHIKV infection and a nurse infected in metropolitan France after direct contact with the blood of a traveler. Four patients had tenosynovitis and pain at wrist pressure, and 1 had life-threatening manifestations. Four CHIKV strains were isolated, including 1 from the patient with the autochthonous case. The complete genomic sequence identified a new CHIKV variant emerging from the East/central African evolutionary lineage. Aedes albopictus, the implicated vector of CHIKV in Indian Ocean islands, has dispersed worldwide in recent decades. High viral loads in patients returning from Indian Ocean islands to countries where Ae. albopictus is prevalent may be a source of epidemics.",2006 Oct,"['Parola, Philippe', 'de Lamballerie, Xavier', 'Jourdan, Jacques', 'Rovery, Clarisse', 'Vaillant, Véronique', 'Minodier, Philippe', 'Brouqui, Philippe', 'Flahault, Antoine', 'Raoult, Didier', 'Charrel, Rémi N.']",Emerg Infect Dis,,,True
13aaa954a9640c1432ca19b75e00c021ab63871b,PMC,Global Public Health Surveillance under New International Health Regulations,http://dx.doi.org/10.3201/eid1207.051497,PMC3291053,16836821,NO-CC CODE,"The new International Health Regulations adopted by the World Health Assembly in May 2005 (IHR 2005) represents a major development in the use of international law for public health purposes. One of the most important aspects of IHR 2005 is the establishment of a global surveillance system for public health emergencies of international concern. This article assesses the surveillance system in IHR 2005 by applying well-established frameworks for evaluating public health surveillance. The assessment shows that IHR 2005 constitutes a major advance in global surveillance from what has prevailed in the past. Effectively implementing the IHR 2005 surveillance objectives requires surmounting technical, resource, governance, legal, and political obstacles. Although IHR 2005 contains some provisions that directly address these obstacles, active support by the World Health Organization and its member states is required to strengthen national and global surveillance capabilities.",2006 Jul,"['Baker, Michael G.', 'Fidler, David P.']",Emerg Infect Dis,,,True
5f8f57b347928e8586fde5b98a1457146a7b1410,PMC,Human Bocavirus in French Children,http://dx.doi.org/10.3201/eid1208.060213,PMC3291226,16965707,NO-CC CODE,"Human bocavirus (HBoV), a new member of the genus Bocavirus in the family Parvoviridae, has been recently associated with respiratory tract infections. We report the epidemiologic and clinical features observed from a 1-year retrospective study of HBoV infection in young children hospitalized with a respiratory tract infection.",2006 Aug,"['Foulongne, Vincent', 'Olejnik, Yann', 'Perez, Virginie', 'Elaerts, Stéphane', 'Rodière, Michel', 'Segondy, Michel']",Emerg Infect Dis,,,True
177dc1a77c417696ac36875b7fc3cefec3ec8d55,PMC,"Bocavirus Infection in Hospitalized Children, South Korea",http://dx.doi.org/10.3201/eid1208.060261,PMC3291229,16965708,NO-CC CODE,"This study presents the first evidence of human bocavirus infection in South Korean children. The virus was detected in 27 (8.0%) of 336 tested specimens, including 17 (7.5%) of 225 virus-negative specimens, collected from children with acute lower respiratory tract infection.",2006 Aug,"['Chung, Ju-Young', 'Han, Tae Hee', 'Kim, Chang Keun', 'Kim, Sang Woo']",Emerg Infect Dis,,,True
c411d679c075271c621362069cea8014264d6c67,PMC,Virulent Epidemics and Scope of Healthcare Workers' Duty of Care,http://dx.doi.org/10.3201/eid1208.060360,PMC3291234,16965703,NO-CC CODE,"The phrase ""duty of care"" is, at best, too vague and, at worst, ethically dangerous. The nature and scope of the duty need to be determined, and conflicting duties must be recognized and acknowledged. Duty of care is neither fixed nor absolute but heavily dependent on context. The normal risk level of the working environment, the healthcare worker's specialty, the likely harm and benefits of treatment, and the competing obligations deriving from the worker's multiple roles will all influence the limits of the duty of care. As experts anticipate the arrival of an avian influenza pandemic in humans, discussion of this matter is urgently needed.",2006 Aug,"Sokol, Daniel K.",Emerg Infect Dis,,,True
c776741a382b4b6a00d9deb5f97bc2fb113bef74,PMC,Evaluating Detection of an Inhalational Anthrax Outbreak,http://dx.doi.org/10.3201/eid1212.060331,PMC3291344,17326949,NO-CC CODE,"Timely detection of an inhalational anthrax outbreak is critical for clinical and public health management. Syndromic surveillance has received considerable investment, but little is known about how it will perform relative to routine clinical case finding for detection of an inhalational anthrax outbreak. We conducted a simulation study to compare clinical case finding with syndromic surveillance for detection of an outbreak of inhalational anthrax. After simulated release of 1 kg of anthrax spores, the proportion of outbreaks detected first by syndromic surveillance was 0.59 at a specificity of 0.9 and 0.28 at a specificity of 0.975. The mean detection benefit of syndromic surveillance was 1.0 day at a specificity of 0.9 and 0.32 days at a specificity of 0.975. When syndromic surveillance was sufficiently sensitive to detect a substantial proportion of outbreaks before clinical case finding, it generated frequent false alarms.",2006 Dec,"['Buckeridge, David L.', 'Owens, Douglas K.', 'Switzer, Paul', 'Frank, John', 'Musen, Mark A.']",Emerg Infect Dis,,,True
c963e012bdc62568b37159f8a60ab687c8489e3c,PMC,Evaluating Detection of an Inhalational Anthrax Outbreak,http://dx.doi.org/10.3201/eid1212.060331,PMC3291344,17326949,NO-CC CODE,"Timely detection of an inhalational anthrax outbreak is critical for clinical and public health management. Syndromic surveillance has received considerable investment, but little is known about how it will perform relative to routine clinical case finding for detection of an inhalational anthrax outbreak. We conducted a simulation study to compare clinical case finding with syndromic surveillance for detection of an outbreak of inhalational anthrax. After simulated release of 1 kg of anthrax spores, the proportion of outbreaks detected first by syndromic surveillance was 0.59 at a specificity of 0.9 and 0.28 at a specificity of 0.975. The mean detection benefit of syndromic surveillance was 1.0 day at a specificity of 0.9 and 0.32 days at a specificity of 0.975. When syndromic surveillance was sufficiently sensitive to detect a substantial proportion of outbreaks before clinical case finding, it generated frequent false alarms.",2006 Dec,"['Buckeridge, David L.', 'Owens, Douglas K.', 'Switzer, Paul', 'Frank, John', 'Musen, Mark A.']",Emerg Infect Dis,,,True
38c2570bc1b51e286def9e0dcf27ec6bcf893dd8,PMC,Review of Bats and SARS,http://dx.doi.org/10.3201/eid1212.060401,PMC3291347,17326933,NO-CC CODE,"Bats have been identified as a natural reservoir for an increasing number of emerging zoonotic viruses, including henipaviruses and variants of rabies viruses. Recently, we and another group independently identified several horseshoe bat species (genus Rhinolophus) as the reservoir host for a large number of viruses that have a close genetic relationship with the coronavirus associated with severe acute respiratory syndrome (SARS). Our current research focused on the identification of the reservoir species for the progenitor virus of the SARS coronaviruses responsible for outbreaks during 2002–2003 and 2003–2004. In addition to SARS-like coronaviruses, many other novel bat coronaviruses, which belong to groups 1 and 2 of the 3 existing coronavirus groups, have been detected by PCR. The discovery of bat SARS-like coronaviruses and the great genetic diversity of coronaviruses in bats have shed new light on the origin and transmission of SARS coronaviruses.",2006 Dec,"['Wang, Lin-Fa', 'Shi, Zhengli', 'Zhang, Shuyi', 'Field, Hume', 'Daszak, Peter', 'Eaton, Bryan T.']",Emerg Infect Dis,,,True
596e1ce4967dd7cbb1fbe4c6b52c3910fee48987,PMC,Long-term Psychological and Occupational Effects of Providing Hospital Healthcare during SARS Outbreak,http://dx.doi.org/10.3201/eid1212.060584,PMC3291360,17326946,NO-CC CODE,"Healthcare workers (HCWs) found the 2003 outbreak of severe acute respiratory syndrome (SARS) to be stressful, but the long-term impact is not known. From 13 to 26 months after the SARS outbreak, 769 HCWs at 9 Toronto hospitals that treated SARS patients and 4 Hamilton hospitals that did not treat SARS patients completed a survey of several adverse outcomes. Toronto HCWs reported significantly higher levels of burnout (p = 0.019), psychological distress (p<0.001), and posttraumatic stress (p<0.001). Toronto workers were more likely to have reduced patient contact and work hours and to report behavioral consequences of stress. Variance in adverse outcomes was explained by a protective effect of the perceived adequacy of training and support and by a provocative effect of maladaptive coping style and other individual factors. The results reinforce the value of effective staff support and training in preparation for future outbreaks.",2006 Dec,"['Maunder, Robert G.', 'Lancee, William J.', 'Balderson, Kenneth E.', 'Bennett, Jocelyn P.', 'Borgundvaag, Bjug', 'Evans, Susan', 'Fernandes, Christopher M.B.', 'Goldbloom, David S.', 'Gupta, Mona', 'Hunter, Jonathan J.', 'Hall, Linda McGillis', 'Nagle, Lynn M.', 'Pain, Clare', 'Peczeniuk, Sonia S.', 'Raymond, Glenna', 'Read, Nancy', 'Rourke, Sean B.', 'Steinberg, Rosalie J.', 'Stewart, Thomas E.', 'Coke, Susan VanDeVelde', 'Veldhorst, Georgina G.', 'Wasylenki, Donald A.']",Emerg Infect Dis,,,True
62aad0910cdeceb067d2847f0c145c5c785e7085,PMC,"Laboratory Exposure to Influenza A H2N2, Germany, 2004–2005",http://dx.doi.org/10.3201/eid1212.060664,PMC3291362,17354343,NO-CC CODE,,2006 Dec,"['Schrauder, Annette', 'Schweiger, Brunhilde', 'Buchholz, Udo', 'Haas, Walter', 'Sagebiel, Daniel', 'Guignard, Adrienne', 'Hellenbrand, Wiebke']",Emerg Infect Dis,,,True
402b53bd0eb35adc900cc262a1c20d5ef198aeb6,PMC,"Risk Factors for Human Infection with Avian Influenza A H5N1, Vietnam, 2004",http://dx.doi.org/10.3201/eid1212.060829,PMC3291373,17326934,NO-CC CODE,"To evaluate risk factors for human infection with influenza A subtype H5N1, we performed a matched case-control study in Vietnam. We enrolled 28 case-patients who had laboratory-confirmed H5N1 infection during 2004 and 106 age-, sex-, and location-matched control-respondents. Data were analyzed by matched-pair analysis and multivariate conditional logistic regression. Factors that were independently associated with H5N1 infection were preparing sick or dead poultry for consumption <7 days before illness onset (matched odds ratio [OR] 8.99, 95% confidence interval [CI] 0.98–81.99, p = 0.05), having sick or dead poultry in the household <7 days before illness onset (matched OR 4.94, 95% CI 1.21–20.20, p = 0.03), and lack of an indoor water source (matched OR 6.46, 95% CI 1.20–34.81, p = 0.03). Factors not significantly associated with infection were raising healthy poultry, preparing healthy poultry for consumption, and exposure to persons with an acute respiratory illness.",2006 Dec,"['Dinh, Pham Ngoc', 'Long, Hoang Thuy', 'Tien, Nguyen Thi Kim', 'Hien, Nguyen Tran', 'Mai, Le Thi Quynh', 'Phong, Le Hong', 'Van Tuan, Le', 'Van Tan, Hoang', 'Nguyen, Nguyen Binh', 'Van Tu, Phan', 'Phuong, Nguyen Thi Minh', None]",Emerg Infect Dis,,,True
d20952c61aec1485523305c6c24fb757b5c27dba,PMC,"Coordinated Response to SARS, Vancouver, Canada",http://dx.doi.org/10.3201/eid1201.050327,PMC3291383,16494736,NO-CC CODE,"Two Canadian urban areas received travelers with severe acute respiratory syndrome (SARS) before the World Health Organization issued its alert. By July 2003, Vancouver had identified 5 cases (4 imported); Toronto reported 247 cases (3 imported) and 43 deaths. Baseline preparedness for pandemic threats may account for the absence of sustained transmission and fewer cases of SARS in Vancouver.",2006 Jan,"['Skowronski, Danuta M.', 'Petric, Martin', 'Daly, Patricia', 'Parker, Robert A.', 'Bryce, Elizabeth', 'Doyle, Patrick W.', 'Noble, Michael A.', 'Roscoe, Diane L.', 'Tomblin, Joan', 'Yang, Tung C.', 'Krajden, Mel', 'Patrick, David M.', 'Pourbohloul, Babak', 'Goh, Swee Han', 'Bowie, William R.', 'Booth, Tim F.', 'Tweed, S. Aleina', 'Perry, Thomas L.', 'McGeer, Allison', 'Brunham, Robert C.']",Emerg Infect Dis,,,True
e6be23c89a2a35984244b66372f9ec6bcc549839,PMC,Pathogen Transmission and Clinic Scheduling,http://dx.doi.org/10.3201/eid1201.050349,PMC3291384,16494737,NO-CC CODE,"We developed a model of pathogen dissemination in the outpatient clinic that incorporates key kinetic aspects of the transmission process, as well as uncertainty regarding whether or not each incident patient is contagious. Assigning appointments late in the day to patients suspected of being infectious should decrease pathogen dissemination.",2006 Jan,"['Hotchkiss, John R.', 'Strike, David G.', 'Crooke, Philip S.']",Emerg Infect Dis,,,True
22a307b3c964d16821fcf30a809d1cbd408939f8,PMC,SARS–associated Coronavirus Replication in Cell Lines,http://dx.doi.org/10.3201/eid1201.050496,PMC3291385,16494729,NO-CC CODE,"Given the potential for laboratory-associated severe acute respiratory syndrome–associated coronavirus (SARS-CoV) infections, we must know which cell lines are susceptible to the virus. We investigated 21 cell lines routinely used for virus isolation or research. After infection with SARS-CoV, cells were observed for cytopathic effects, and quantitative real-time polymerase chain reaction was used to measure ongoing viral replication. An indirect immunofluorescence assay was also used as a confirmatory test. The study identified 10 new cell lines capable of supporting the replication of SARS-CoV and confirmed the susceptibility of 4 cell lines previously reported. This study shows that SARS-CoV can be isolated in several cell lines commonly used for diagnostic or research purposes. It also shows that SARS-CoV can achieve high titers in several cell lines, sometimes in the absence of specific cytopathic effects.",2006 Jan,"['Kaye, Matthew', 'Druce, Julian', 'Tran, Thomas', 'Kostecki, Renata', 'Chibo, Doris', 'Morris, Jessica', 'Catton, Mike', 'Birch, Chris']",Emerg Infect Dis,,,True
8890802024d971865d693869aa338494806233b4,PMC,Pandemic Influenza Threat and Preparedness,http://dx.doi.org/10.3201/eid1201.050983,PMC3291399,16494721,NO-CC CODE,"The threat of a human influenza pandemic has greatly increased over the past several years with the emergence of highly virulent avian influenza viruses, notably H5N1 viruses, which have infected humans in several Asian and European countries. Previous influenza pandemics have arrived with little or no warning, but the current widespread circulation of H5N1 viruses among avian populations and their potential for increased transmission to humans and other mammalian species may afford us an unprecedented opportunity to prepare for the next pandemic threat. The US Department of Health and Human Services is coordinating a national strategy to respond to an influenza pandemic that involves multiple agencies, including the Centers for Disease Control and Prevention, the Food and Drug Administration, and the National Institutes of Health (NIH). Within NIH, the National Institute of Allergy and Infectious Diseases (NIAID) conducts basic and clinical research to develop new vaccine technologies and antiviral drugs against influenza viruses. We describe recent research progress in preparing for pandemic influenza.",2006 Jan,"Fauci, Anthony S.",Emerg Infect Dis,,,True
d66d18ad33170f29a2279d8cc4ca3e31bdee67f0,PMC,H5N1 Outbreaks and Enzootic Influenza,http://dx.doi.org/10.3201/eid1201.051024,PMC3291402,16494709,NO-CC CODE,"Ongoing outbreaks of H5N1 avian influenza in migratory waterfowl, domestic poultry, and humans in Asia during the summer of 2005 present a continuing, protean pandemic threat. We review the zoonotic source of highly pathogenic H5N1 viruses and their genesis from their natural reservoirs. The acquisition of novel traits, including lethality to waterfowl, ferrets, felids, and humans, indicates an expanding host range. The natural selection of nonpathogenic viruses from heterogeneous subpopulations cocirculating in ducks contributes to the spread of H5N1 in Asia. Transmission of highly pathogenic H5N1 from domestic poultry back to migratory waterfowl in western China has increased the geographic spread. The spread of H5N1 and its likely reintroduction to domestic poultry increase the need for good agricultural vaccines. In fact, the root cause of the continuing H5N1 pandemic threat may be the way the pathogenicity of H5N1 viruses is masked by cocirculating influenza viruses or bad agricultural vaccines.",2006 Jan,"['Webster, Robert G.', 'Peiris, Malik', 'Chen, Honglin', 'Guan, Yi']",Emerg Infect Dis,,,True
c13a9965ccf255b75e8c2d08b3da78f73e77fbc5,PMC,Vaccines for Pandemic Influenza,http://dx.doi.org/10.3201/eid1201.051147,PMC3291408,16494720,NO-CC CODE,"Recent outbreaks of highly pathogenic avian influenza in Asia and associated human infections have led to a heightened level of awareness and preparation for a possible influenza pandemic. Vaccination is the best option by which spread of a pandemic virus could be prevented and severity of disease reduced. Production of live attenuated and inactivated vaccine seed viruses against avian influenza viruses, which have the potential to cause pandemics, and their testing in preclinical studies and clinical trials will establish the principles and ensure manufacturing experience that will be critical in the event of the emergence of such a virus into the human population. Studies of such vaccines will also add to our understanding of the biology of avian influenza viruses and their behavior in mammalian hosts.",2006 Jan,"['Luke, Catherine J.', 'Subbarao, Kanta']",Emerg Infect Dis,,,True
2767c1eb3cdc745405ed67f0f92b226ee9b33b79,PMC,Molecular Pathogenesis of Virus Infections,http://dx.doi.org/10.3201/eid1201.051305,PMC3291412,,NO-CC CODE,,2006 Jan,"Buller, Robert",Emerg Infect Dis,,,False
7dd61ea67b85e4605fd732fd0208d5eb27822ded,PMC,"The Germ Freak's Guide to Outwitting Colds and Flu: Guerilla Tactics to Keep Yourself Healthy at Home, at Work, and in the World",http://dx.doi.org/10.3201/eid1201.051309,PMC3291413,,NO-CC CODE,,2006 Jan,"Sessions, Kimberly",Emerg Infect Dis,,,False
4c7759f1da349496e9308d9f4f0d4e071a23c19f,PMC,"Nonpharmaceutical Interventions for Pandemic Influenza, International Measures",http://dx.doi.org/10.3201/eid1201.051370,PMC3291414,16494722,NO-CC CODE,"Since global availability of vaccine and antiviral agents against influenza caused by novel human subtypes is insufficient, the World Health Organization (WHO) recommends nonpharmaceutical public health interventions to contain infection, delay spread, and reduce the impact of pandemic disease. Virus transmission characteristics will not be completely known in advance, but difficulties in influenza control typically include peak infectivity early in illness, a short interval between cases, and to a lesser extent, transmission from persons with incubating or asymptomatic infection. Screening and quarantining entering travelers at international borders did not substantially delay virus introduction in past pandemics, except in some island countries, and will likely be even less effective in the modern era. Instead, WHO recommends providing information to international travelers and possibly screening travelers departing countries with transmissible human infection. The principal focus of interventions against pandemic influenza spread should be at national and community levels rather than international borders.",2006 Jan,,Emerg Infect Dis,,,True
e159298c6d214ba5e950ef1cda327cf5a88326b8,PMC,"Nonpharmaceutical Interventions for Pandemic Influenza, National and Community Measures",http://dx.doi.org/10.3201/eid1201.051371,PMC3291415,16494723,NO-CC CODE,"The World Health Organization's recommended pandemic influenza interventions, based on limited data, vary by transmission pattern, pandemic phase, and illness severity and extent. In the pandemic alert period, recommendations include isolation of patients and quarantine of contacts, accompanied by antiviral therapy. During the pandemic period, the focus shifts to delaying spread and reducing effects through population-based measures. Ill persons should remain home when they first become symptomatic, but forced isolation and quarantine are ineffective and impractical. If the pandemic is severe, social distancing measures such as school closures should be considered. Nonessential domestic travel to affected areas should be deferred. Hand and respiratory hygiene should be routine; mask use should be based on setting and risk, and contaminated household surfaces should be disinfected. Additional research and field assessments during pandemics are essential to update recommendations. Legal authority and procedures for implementing interventions should be understood in advance and should respect cultural differences and human rights.",2006 Jan,,Emerg Infect Dis,,,True
36c97bef26a4934b9f543c3f67f0ab9cfa55e6b5,PMC,Canine Coronavirus Highly Pathogenic for Dogs,http://dx.doi.org/10.3201/eid1203.050839,PMC3291441,16704791,NO-CC CODE,"Canine coronavirus (CCoV) is usually responsible for mild, self-limiting infections restricted to the enteric tract. We report an outbreak of fatal disease in puppies caused by a pathogenic variant of CCoV that was isolated from organs with severe lesions.",2006 Mar,"['Buonavoglia, Canio', 'Decaro, Nicola', 'Martella, Vito', 'Elia, Gabriella', 'Campolo, Marco', 'Desario, Costantina', 'Castagnaro, Massimo', 'Tempesta, Maria']",Emerg Infect Dis,,,True
080315372a3c246497a2f111b90af0c956032487,PMC,Detecting Emerging Diseases in Farm Animals through Clinical Observations,http://dx.doi.org/10.3201/eid1202.050498,PMC3293432,16494743,NO-CC CODE,"Predicting emerging diseases is among the most difficult challenges facing researchers and health managers. We present available approaches and tools to detect emerging diseases in animals based on clinical observations of farm animals by veterinarians. Three information systems are described and discussed: Veterinary Practitioner Aided Disease Surveillance in New Zealand, the Rapid Syndrome Validation Project—Animal in the United States, and ""émergences"" in France. These systems are based on syndromic surveillance with the notification of every case or of specific clinical syndromes or on the notification of atypical clinical cases. Data are entered by field veterinarians into forms available through Internet-accessible devices. Beyond challenges of implementing new information systems, minimizing economic and health effects from emerging diseases in animals requires strong synergies across a group of field partners, in research, and in international animal and public health customs and practices.",2006 Feb,"[""Vourc'h, Gwenaël"", 'Bridges, Victoria E.', 'Gibbens, Jane', 'De Groot, Brad D.', 'McIntyre, Lachlan', 'Poland, Roger', 'Barnouin, Jacques']",Emerg Infect Dis,,,True
53e010f880f4fc5f6a6832c81cbae2342f98b210,PMC,Real-time Forecast of Multiphase Outbreak,http://dx.doi.org/10.3201/eid1201.050396,PMC3293463,16494728,NO-CC CODE,"We used a single equation with discrete phases to fit the daily cumulative case data from the 2003 severe acute respiratory syndrome outbreak in Toronto. This model enabled us to estimate turning points and case numbers during the 2 phases of this outbreak. The 3 estimated turning points are March 25, April 27, and May 24. The estimated case number during the first phase of the outbreak between February 23 and April 26 is 140.53 (95% confidence interval [CI] 115.88–165.17) if we use the data from February 23 to April 4; and 249 (95% CI: 246.67–251.25) at the end of the second phase on June 12 if we use the data from April 28 to June 4. The second phase can be detected by using case data just 3 days past the beginning of the phase, while the first and third turning points can be identified only ≈10 days afterwards. Our modeling procedure provides insights into ongoing outbreaks that may facilitate real-time public health responses.",2006 Jan,"['Hsieh, Ying-Hen', 'Cheng, Yuan-Sen']",Emerg Infect Dis,,,True
12c156dc659a9b4c3008ce4d6d10f464d60b5b65,PMC,Real-time Estimates in Early Detection of SARS,http://dx.doi.org/10.3201/eid1201.050593,PMC3293464,16494726,NO-CC CODE,"We propose a Bayesian statistical framework for estimating the reproduction number R early in an epidemic. This method allows for the yet-unrecorded secondary cases if the estimate is obtained before the epidemic has ended. We applied our approach to the severe acute respiratory syndrome (SARS) epidemic that started in February 2003 in Hong Kong. Temporal patterns of R estimated after 5, 10, and 20 days were similar. Ninety-five percent credible intervals narrowed when more data were available but stabilized after 10 days. Using simulation studies of SARS-like outbreaks, we have shown that the method may be used for early monitoring of the effect of control measures.",2006 Jan,"['Cauchemez, Simon', 'Boëlle, Pierre-Yves', 'Donnelly, Christl A.', 'Ferguson, Neil M', 'Thomas, Guy', 'Leung, Gabriel M.', 'Hedley, Anthony J', 'Anderson, Roy M.', 'Valleron, Alain-Jacques']",Emerg Infect Dis,,,True
27c85eb0542256f6599ba43e90986abfdb1ddc5b,PMC,Influenza-associated Deaths in Tropical Singapore,http://dx.doi.org/10.3201/eid1201.050826,PMC3293465,16494727,NO-CC CODE,"We used a regression model to examine the impact of influenza on death rates in tropical Singapore for the period 1996–2003. Influenza A (H3N2) was the predominant circulating influenza virus subtype, with consistently significant and robust effect on mortality rates. Influenza was associated with an annual death rate from all causes, from underlying pneumonia and influenza, and from underlying circulatory and respiratory conditions of 14.8 (95% confidence interval 9.8–19.8), 2.9 (1.0–5.0), and 11.9 (8.3–15.7) per 100,000 person-years, respectively. These results are comparable with observations in the United States and subtropical Hong Kong. An estimated 6.5% of underlying pneumonia and influenza deaths were attributable to influenza. The proportion of influenza-associated deaths was 11.3 times higher in persons age >65 years than in the general population. Our findings support the need for influenza surveillance and annual influenza vaccination for at-risk populations in tropical countries.",2006 Jan,"['Chow, Angela', 'Ma, Stefan', 'Ling, Ai Ee', 'Chew, Suok Kai']",Emerg Infect Dis,,,True
4566e8328c0ee3f5a68f04651dafb852786cb121,PMC,Occupational Health Response to SARS,http://dx.doi.org/10.3201/eid1101.040637,PMC3294325,15714660,NO-CC CODE,,2005 Jan,"['Koh, David', 'Lim, Meng-Kin', 'Ong, Choon-Nam', 'Chia, Sin-Eng']",Emerg Infect Dis,,,True
a8aa723ba5e98887cee2b63ca3cfe956c4a5933b,PMC,Border Screening for SARS,http://dx.doi.org/10.3201/eid1101.040835,PMC3294328,15705315,NO-CC CODE,"With the rapid international spread of severe acute respiratory syndrome (SARS) from March through May 2003, Canada introduced various measures to screen airplane passengers at selected airports for symptoms and signs of SARS. The World Health Organization requested that all affected areas screen departing passengers for SARS symptoms. In spite of intensive screening, no SARS cases were detected. SARS has an extremely low prevalence, and the positive predictive value of screening is essentially zero. Canadian screening results raise questions about the effectiveness of available screening measures for SARS at international borders.",2005 Jan,"['St. John, Ronald K.', 'King, Arlene', 'de Jong, Dick', 'Bodie-Collins, Margaret', 'Squires, Susan G.', 'Tam, Theresa WS']",Emerg Infect Dis,,,True
0a3d78fb4b228cdc20e48fcc96f9da3f92ce1207,PMC,SARS-CoV Sampling from 3 Portals,http://dx.doi.org/10.3201/eid1101.040645,PMC3294345,15714659,NO-CC CODE,,2005 Jan,"Tong, Tommy R.",Emerg Infect Dis,,,True
1fc650db3448c38d83fbe7cdd07db4f45dda9223,PMC,"Anti–SARS-CoV Immunoglobulin G in Healthcare Workers, Guangzhou, China",http://dx.doi.org/10.3201/eid1101.040138,PMC3294349,15705328,NO-CC CODE,"To determine the prevalence of inapparent infection with severe acute respiratory syndrome (SARS) among healthcare workers, we performed a serosurvey to test for immunoglobulin (Ig) G antibodies to the SARS coronavirus (SARS-CoV) among 1,147 healthcare workers in 3 hospitals that admitted SARS patients in mid-May 2003. Among them were 90 healthcare workers with SARS. As a reference group, 709 healthcare workers who worked in 2 hospitals that never admitted any SARS patients were similarly tested. The seroprevalence rate was 88.9% (80/90) for healthcare workers with SARS and 1.4% (15/1,057) for healthcare workers who were apparently healthy. The seroprevalence in the reference group was 0.4% (3/709). These findings suggest that inapparent infection is uncommon. Low level of immunity among unaffected healthcare workers reinforces the need for adequate personal protection and other infection control measures in hospitals to prevent future epidemics.",2005 Jan,"['Chen, Wei-Qing', 'Lu, Ci-Yong', 'Wong, Tze-Wai', 'Ling, Wen-Hua', 'Lin, Zhong-Ning', 'Hao, Yuan-Tao', 'Liu, Qing', 'Fang, Ji-Qian', 'He, Yun', 'Luo, Fu-Tian', 'Jing, Jin', 'Ling, Li', 'Ma, Xiang', 'Liu, Yi-Min', 'Chen, Gui-Hua', 'Huang, Jian', 'Jiang, Yuan-Sen', 'Jiang, Wen-Qi', 'Zou, He-Qun', 'Yan, Guang-Mei']",Emerg Infect Dis,,,True
615e5a74d3b54ce5e9d1a5dfda4187c1d99a8903,PMC,"SARS Clinical Features, United States, 2003",http://dx.doi.org/10.3201/eid1101.040585,PMC3294350,15705339,NO-CC CODE,"We compared the clinical features of 8 U.S. case-patients with laboratory-confirmed severe acute respiratory syndrome (SARS) to 65 controls who tested negative for SARS coronavirus (SARS-CoV) infection. Shortness of breath, vomiting, diarrhea, progressive bilateral infiltrates on chest radiograph, and need for supplemental oxygen were significantly associated with confirmed SARS-CoV infection.",2005 Jan,"['Srikantiah, Padmini', 'Charles, Myrna D.', 'Reagan, Sarah', 'Clark, Thomas A.', 'Pletz, Mathias W.R.', 'Patel, Priti R.', 'Hoekstra, Robert M.', 'Lingappa, Jairam', 'Jernigan, John A.', 'Fischer, Marc', None]",Emerg Infect Dis,,,True
310df0148d6a22a47355143c065a8b6cef8edd41,PMC,A Novel Paramyxovirus?,http://dx.doi.org/10.3201/eid1101.040653,PMC3294354,15705331,NO-CC CODE,"In public databases, we identified sequences reported as human genes expressed in kidney mesangial cells. The similarity of these genes to paramyxovirus matrix, fusion, and phosphoprotein genes suggests that they are derived from a novel paramyxovirus. These genes are sufficiently unique to suggest the existence of a novel paramyxovirus genus.",2005 Jan,"['Basler, Christopher F.', 'García-Sastre, Adolfo', 'Palese, Peter']",Emerg Infect Dis,,,True
276d1d1c20336ca2a6f54c7a95507001917e4c44,PMC,Tracing SARS-Coronavirus Variant with Large Genomic Deletion,http://dx.doi.org/10.3201/eid1101.040544,PMC3294368,15714661,NO-CC CODE,,2005 Jan,"['Chiu, Rossa W.K.', 'Chim, Stephen S.C.', 'Tong, Yu-kwan', 'Fung, Kitty S.C.', 'Chan, Paul K.S.', 'Zhao, Guo-ping', 'Lo, Y.M. Dennis']",Emerg Infect Dis,,,True
f8e19f9d339fc06f51381d54969121f75fcbaf0f,PMC,"Risk Factors for Pandemic (H1N1) 2009 Virus Seroconversion among Hospital Staff, Singapore",http://dx.doi.org/10.3201/eid1610.100516,PMC3294397,20875280,NO-CC CODE,"We describe incidence and risk factors for pandemic (H1N1) 2009 virus infection in healthcare personnel during the June–September 2009 epidemic in Singapore. Personnel contributed 3 serologic samples during June–October 2009, with seroconversion defined as a >4-fold increase in hemagglutination inhibition titers to pandemic (H1N1) 2009. Of 531 participants, 35 showed evidence of seroconversion. Seroconversion rates were highest in nurses (28/290) and lowest in allied health staff (2/116). Significant risk factors on multivariate analysis were being a nurse (adjusted odds ratio [aOR] 4.5, 95% confidence interval [CI] 1.0–19.6) and working in pandemic (H1N1) 2009 isolation wards (aOR 4.5, 95% CI 1.3–15.6). Contact with pandemic (H1N1) 2009–infected colleagues (aOR 2.5, 95% CI 0.9–6.6) and larger household size (aOR 1.2, 95% CI 1.0–1.4) were of borderline significance. Our study suggests that seroconversion was associated with occupational and nonoccupational risk factors.",2010 Oct,"['Chen, Mark I.C.', 'Lee, Vernon J.M.', 'Barr, Ian', 'Lin, Cui', 'Goh, Rachelle', 'Lee, Caroline', 'Singh, Baldev', 'Tan, Jessie', 'Lim, Wei-Yen', 'Cook, Alex R.', 'Ang, Brenda', 'Chow, Angela', 'Tan, Boon Huan', 'Loh, Jimmy', 'Shaw, Robert', 'Chia, Kee Seng', 'Lin, Raymond T.P.', 'Leo, Yee Sin']",Emerg Infect Dis,,,True
ff7d49ac4008f60ef9c5a437e0d504dcefd1246f,PMC,"Internet Search Limitations and Pandemic Influenza, Singapore",http://dx.doi.org/10.3201/eid1610.100840,PMC3294408,20875307,NO-CC CODE,,2010 Oct,"['Cook, Alex R.', 'Chen, Mark I.C.', 'Lin, Raymond Tzer Pin']",Emerg Infect Dis,,,True
dca62735df89a3903dc137e511095984c2d9f21a,PMC,Outbreaks of Pandemic (H1N1) 2009 and Seasonal Influenza A (H3N2) on Cruise Ship,http://dx.doi.org/10.3201/eid1611.100477,PMC3294517,21029531,NO-CC CODE,"To determine the extent and pattern of influenza transmission and effectiveness of containment measures, we investigated dual outbreaks of pandemic (H1N1) 2009 and influenza A (H3N2) that had occurred on a cruise ship in May 2009. Of 1,970 passengers and 734 crew members, 82 (3.0%) were infected with pandemic (H1N1) 2009 virus, 98 (3.6%) with influenza A (H3N2) virus, and 2 (0.1%) with both. Among 45 children who visited the ship’s childcare center, infection rate for pandemic (H1N1) 2009 was higher than that for influenza A (H3N2) viruses. Disembarked passengers reported a high level of compliance with isolation and quarantine recommendations. We found 4 subsequent cases epidemiologically linked to passengers but no evidence of sustained transmission to the community or passengers on the next cruise. Among this population of generally healthy passengers, children seemed more susceptible to pandemic (H1N1) 2009 than to influenza (H3N2) viruses. Intensive disease control measures successfully contained these outbreaks.",2010 Nov,"['Ward, Kate A.', 'Armstrong, Paul', 'McAnulty, Jeremy M.', 'Iwasenko, Jenna M.', 'Dwyer, Dominic E.']",Emerg Infect Dis,,,True
02db9273596bf34a72c596189ed95dab16e683e4,PMC,Comparison of 3 Infrared Thermal Detection Systems and Self-Report for Mass Fever Screening,http://dx.doi.org/10.3201/eid1611.100703,PMC3294528,21029528,NO-CC CODE,"Despite limited evidence regarding their utility, infrared thermal detection systems (ITDS) are increasingly being used for mass fever detection. We compared temperature measurements for 3 ITDS (FLIR ThermoVision A20M [FLIR Systems Inc., Boston, MA, USA], OptoTherm Thermoscreen [OptoTherm Thermal Imaging Systems and Infrared Cameras Inc., Sewickley, PA, USA], and Wahl Fever Alert Imager HSI2000S [Wahl Instruments Inc., Asheville, NC, USA]) with oral temperatures (>100°F = confirmed fever) and self-reported fever. Of 2,873 patients enrolled, 476 (16.6%) reported a fever, and 64 (2.2%) had a confirmed fever. Self-reported fever had a sensitivity of 75.0%, specificity 84.7%, and positive predictive value 10.1%. At optimal cutoff values for detecting fever, temperature measurements by OptoTherm and FLIR had greater sensitivity (91.0% and 90.0%, respectively) and specificity (86.0% and 80.0%, respectively) than did self-reports. Correlations between ITDS and oral temperatures were similar for OptoTherm (ρ = 0.43) and FLIR (ρ = 0.42) but significantly lower for Wahl (ρ = 0.14; p<0.001). When compared with oral temperatures, 2 systems (OptoTherm and FLIR) were reasonably accurate for detecting fever and predicted fever better than self-reports.",2010 Nov,"['Nguyen, An V.', 'Cohen, Nicole J.', 'Lipman, Harvey', 'Brown, Clive M.', 'Molinari, Noelle-Angelique', 'Jackson, William L.', 'Kirking, Hannah', 'Szymanowski, Paige', 'Wilson, Todd W.', 'Salhi, Bisan A.', 'Roberts, Rebecca R.', 'Stryker, David W.', 'Fishbein, Daniel B.']",Emerg Infect Dis,,,True
11618b8e0169b98b7c4f0b06f900d3fe4c853ab3,PMC,Reassortant Group A Rotavirus from Straw-colored Fruit Bat (Eidolon helvum),http://dx.doi.org/10.3201/eid1612.101089,PMC3294550,21122212,NO-CC CODE,"Bats are known reservoirs of viral zoonoses. We report genetic characterization of a bat rotavirus (Bat/KE4852/07) detected in the feces of a straw-colored fruit bat (Eidolon helvum). Six bat rotavirus genes (viral protein [VP] 2, VP6, VP7, nonstructural protein [NSP] 2, NSP3, and NSP5) shared ancestry with other mammalian rotaviruses but were distantly related. The VP4 gene was nearly identical to that of human P[6] rotavirus strains, and the NSP4 gene was closely related to those of previously described mammalian rotaviruses, including human strains. Analysis of partial sequence of the VP1 gene indicated that it was distinct from cognate genes of other rotaviruses. No sequences were obtained for the VP3 and NSP1 genes of the bat rotavirus. This rotavirus was designated G25-P[6]-I15-R8(provisional)-C8-Mx-Ax-N8-T11-E2-H10. Results suggest that several reassortment events have occurred between human, animal, and bat rotaviruses. Several additional rotavirus strains were detected in bats.",2010 Dec,"['Esona, Mathew D.', 'Mijatovic-Rustempasic, Slavica', 'Conrardy, Christina', 'Tong, Suxiang', 'Kuzmin, Ivan V.', 'Agwanda, Bernard', 'Breiman, Robert F.', 'Banyai, Krisztian', 'Niezgoda, Michael', 'Rupprecht, Charles E.', 'Gentsch, Jon R.', 'Bowen, Michael D.']",Emerg Infect Dis,,,True
ac6ddd960d11017380374185a61548d6a1c7dba4,PMC,Reassortant Group A Rotavirus from Straw-colored Fruit Bat (Eidolon helvum),http://dx.doi.org/10.3201/eid1612.101089,PMC3294550,21122212,NO-CC CODE,"Bats are known reservoirs of viral zoonoses. We report genetic characterization of a bat rotavirus (Bat/KE4852/07) detected in the feces of a straw-colored fruit bat (Eidolon helvum). Six bat rotavirus genes (viral protein [VP] 2, VP6, VP7, nonstructural protein [NSP] 2, NSP3, and NSP5) shared ancestry with other mammalian rotaviruses but were distantly related. The VP4 gene was nearly identical to that of human P[6] rotavirus strains, and the NSP4 gene was closely related to those of previously described mammalian rotaviruses, including human strains. Analysis of partial sequence of the VP1 gene indicated that it was distinct from cognate genes of other rotaviruses. No sequences were obtained for the VP3 and NSP1 genes of the bat rotavirus. This rotavirus was designated G25-P[6]-I15-R8(provisional)-C8-Mx-Ax-N8-T11-E2-H10. Results suggest that several reassortment events have occurred between human, animal, and bat rotaviruses. Several additional rotavirus strains were detected in bats.",2010 Dec,"['Esona, Mathew D.', 'Mijatovic-Rustempasic, Slavica', 'Conrardy, Christina', 'Tong, Suxiang', 'Kuzmin, Ivan V.', 'Agwanda, Bernard', 'Breiman, Robert F.', 'Banyai, Krisztian', 'Niezgoda, Michael', 'Rupprecht, Charles E.', 'Gentsch, Jon R.', 'Bowen, Michael D.']",Emerg Infect Dis,,,False
6e4cf144e298b4825f3717f6e8f03ab2bb7851e9,PMC,Co-detection of Pandemic (H1N1) 2009 Virus and Other Respiratory Pathogens,http://dx.doi.org/10.3201/eid1612.091697,PMC3294579,21122236,NO-CC CODE,"From May through October 2009, a total of 10,624 clinical samples from 23 US states were screened for multiple respiratory pathogen gene targets. Of 3,110 (29.3%) samples positive for pandemic (H1N1) 2009 virus, 28% contained >1 other pathogen, most commonly Staphylococcus aureus (14.7%), Streptococcus pneumoniae (10.2%), and Haemophilus influenzae (3.5%).",2010 Dec,"['Koon, Kassi', 'Sanders, Catherine M.', 'Green, Jessica', 'Malone, Leslie', 'White, Holly', 'Zayas, Delineliz', 'Miller, Rebecca', 'Lu, Stanley', 'Han, Jian']",Emerg Infect Dis,,,True
3454d8f6a1cfd9321ea90568ac0dc0e138859034,PMC,"Prevalence of Henipavirus and Rubulavirus Antibodies in Pteropid Bats, Papua New Guinea",http://dx.doi.org/10.3201/eid1612.100879,PMC3294587,21122242,NO-CC CODE,"To determine seroprevalence of viruses in bats in Papua New Guinea, we sampled 66 bats at 3 locations. We found a seroprevalence of 55% for henipavirus (Hendra or Nipah virus) and 56% for rubulavirus (Tioman or Menangle virus). Notably, 36% of bats surveyed contained antibodies to both types of viruses, indicating concurrent or consecutive infection.",2010 Dec,"['Breed, Andrew C.', 'Yu, Meng', 'Barr, Jennifer A.', 'Crameri, Gary', 'Thalmann, Claudia M.', 'Wang, Lin-Fa']",Emerg Infect Dis,,,True
b01edd6c71207f4ab7f514a7e39267ee2eb8d029,PMC,"Environmental Sampling for Avian Influenza Virus A (H5N1) in Live-Bird Markets, Indonesia",http://dx.doi.org/10.3201/eid1612.100402,PMC3294595,21122218,NO-CC CODE,"To identify environmental sites commonly contaminated by avian influenza virus A (H5N1) in live-bird markets in Indonesia, we investigated 83 markets in 3 provinces in Indonesia. At each market, samples were collected from up to 27 poultry-related sites to assess the extent of contamination. Samples were tested by using real-time reverse transcription–PCR and virus isolation. A questionnaire was used to ascertain types of birds in the market, general infrastructure, and work practices. Thirty-nine (47%) markets showed contamination with avian influenza virus in >1 of the sites sampled. Risk factors were slaughtering birds in the market and being located in West Java province. Protective factors included daily removal of waste and zoning that segregated poultry-related work flow areas. These results can aid in the design of evidence-based programs concerning environmental sanitation, food safety, and surveillance to reduce the risk for avian influenza virus A (H5N1) transmission in live-bird markets.",2010 Dec,"['Indriani, Risa', 'Samaan, Gina', 'Gultom, Anita', 'Loth, Leo', 'Indryani, Sri', 'Adjid, Rma', 'Dharmayanti, Ni Luh Putu Indi', 'Weaver, John', 'Mumford, Elizabeth', 'Lokuge, Kamalini', 'Kelly, Paul M.', None]",Emerg Infect Dis,,,True
72eea61339d1f964cc302b20af2842e8ca77d3bb,PMC,"Bartonella spp. in Bats, Kenya",http://dx.doi.org/10.3201/eid1612.100601,PMC3294596,21122216,NO-CC CODE,"We report the presence and diversity of Bartonella spp. in bats of 13 insectivorous and frugivorous species collected from various locations across Kenya. Bartonella isolates were obtained from 23 Eidolon helvum, 22 Rousettus aegyptiacus, 4 Coleura afra, 7 Triaenops persicus, 1 Hipposideros commersoni, and 49 Miniopterus spp. bats. Sequence analysis of the citrate synthase gene from the obtained isolates showed a wide assortment of Bartonella strains. Phylogenetically, isolates clustered in specific host bat species. All isolates from R. aegyptiacus, C. afra, and T. persicus bats clustered in separate monophyletic groups. In contrast, E. helvum and Miniopterus spp. bats harbored strains that clustered in several groups. Further investigation is needed to determine whether these agents are responsible for human illnesses in the region.",2010 Dec,"['Kosoy, Michael', 'Bai, Ying', 'Lynch, Tarah', 'Kuzmin, Ivan V.', 'Niezgoda, Michael', 'Franka, Richard', 'Agwanda, Bernard', 'Breiman, Robert F.', 'Rupprecht, Charles E.']",Emerg Infect Dis,,,True
2b269d2f3f05bfcd6dd61c1ce2eb19937d338f98,PMC,"Pulmonary Tuberculosis and SARS, China",http://dx.doi.org/10.3201/eid1204.050264,PMC3294680,16715587,NO-CC CODE,,2006 Apr,"['Liu, Wei', 'Fontanet, Arnaud', 'Zhang, Pan-He', 'Zhan, Lin', 'Xin, Zhong-Tao', 'Tang, Fang', 'Baril, Laurence', 'Cao, Wu-Chun']",Emerg Infect Dis,,,True
0b0cc43d86df1f781f1b37dc2e1a5d8e0b12f7ae,PMC,"Confronting Zoonoses, Linking Human and Veterinary Medicine",http://dx.doi.org/10.3201/eid1204.050956,PMC3294691,16704801,NO-CC CODE,"Many of the emerging infectious diseases, including those caused by bioterrorist agents, are zoonoses. Since zoonoses can infect both animals and humans, the medical and veterinary communities should work closely together in clinical, public health, and research settings. In the clinical setting, input from both professions would improve assessments of the risk-benefit ratios of pet ownership, particularly for pet owners who are immunocompromised. In public health, human and animal disease surveillance systems are important in tracking and controlling zoonoses such as avian influenza virus, West Nile virus, and foodborne pathogens. Comparative medicine is the study of disease processes across species, including humans. Physician and veterinarian comparative medicine research teams should be promoted and encouraged to study zoonotic agent-host interactions. These efforts would increase our understanding of how zoonoses expand their host range and would, ultimately, improve prevention and control strategies.",2006 Apr,"Kahn, Laura H.",Emerg Infect Dis,,,True
cbbc88f97eeb4e11fadea3ea628092195e608018,PMC,Manifesting Ecologic and Microbial Connections,http://dx.doi.org/10.3201/eid1204.AC1204,PMC3294718,16715590,NO-CC CODE,,2006 Apr,"Potter, Polyxeni",Emerg Infect Dis,,,True
fe88da3bc7a4ef88f2bd09b88ae8b08ddb37901e,PMC,"Human Bocavirus in Hospitalized Children, South Africa",http://dx.doi.org/10.3201/eid1209.051616,PMC3294732,17073104,NO-CC CODE,,2006 Sep,"['Smuts, Heidi', 'Hardie, Di']",Emerg Infect Dis,,,True
feadeaa76cdeba85792a28babff5332a83ea1c82,PMC,Nosocomial Tuberculosis in India,http://dx.doi.org/10.3201/eid1209.051663,PMC3294738,17073077,NO-CC CODE,"Most high-income countries implement tuberculosis (TB) infection control programs to reduce the risk for nosocomial transmission. However, such control programs are not routinely implemented in India, the country that accounts for the largest number of TB cases in the world. Despite the high prevalence of TB in India and the expected high probability of nosocomial transmission, little is known about nosocomial and occupational TB there. The few available studies suggest that nosocomial TB may be a problem. We review the available data on this topic, describe factors that may facilitate nosocomial transmission in Indian healthcare settings, and consider the feasibility and applicability of various recommended infection control interventions in these settings. Finally, we outline the critical information needed to effectively address the problem of nosocomial transmission of TB in India.",2006 Sep,"['Pai, Madhukar', 'Kalantri, Shriprakash', 'Aggarwal, Ashutosh Nath', 'Menzies, Dick', 'Blumberg, Henry M.']",Emerg Infect Dis,,,True
d5cfc9cea824e7282fc781c7295d0cbeed69dd1c,PMC,"Murine Typhus from Vietnam, Imported into Japan",http://dx.doi.org/10.3201/eid1209.060071,PMC3294741,17073110,NO-CC CODE,,2006 Sep,"['Azuma, Momoyo', 'Nishioka, Yasuhiko', 'Ogawa, Motohiko', 'Takasaki, Tomohiko', 'Sone, Saburo', 'Uchiyama, Tsuneo']",Emerg Infect Dis,,,True
08432fbe941b440c394214311d01a0dd2a29acd6,PMC,"Human Bocavirus Infection among Children, Jordan",http://dx.doi.org/10.3201/eid1209.060417,PMC3294754,17073092,NO-CC CODE,"Human bocavirus was detected in 57 (18.3%) of 312 children with acute respiratory infection (ARI) who required hospitalization in Jordan. It was also detected in 30 (21.7%) of 138 children with severe ARI, in 27 (15.5%) of 174 with mild or moderate disease, and in 41 (72%) of 57 with other pathogens.",2006 Sep,"['Kaplan, Nasser M.', 'Dove, Winifred', 'Abu-Zeid, Ahmad F.', 'Shamoon, Hiyam E.', 'Abd-Eldayem, Sawsan A.', 'Hart, C. Anthony']",Emerg Infect Dis,,,True
298cf2b429e2d9f800d4605192f37da28bec19a0,PMC,"Influenza in Refugees on the Thailand–Myanmar Border, May–October 2009",http://dx.doi.org/10.3201/eid1609.100220,PMC3294974,20735919,NO-CC CODE,"We describe the epidemiology of influenza virus infections in refugees in a camp in rural Southeast Asia during May–October 2009, the first 6 months after identification of pandemic (H1N1) 2009 in Thailand. Influenza A viruses were detected in 20% of patients who had influenza-like illness and in 23% of those who had clinical pneumonia. Seasonal influenza A (H1N1) was the predominant virus circulating during weeks 26–33 (June 25–August 29) and was subsequently replaced by the pandemic strain. A review of passive surveillance for acute respiratory infection did not show an increase in acute respiratory tract infection incidence associated with the arrival of pandemic (H1N1) 2009 in the camp.",2010 Sep,"['Turner, Paul', 'Turner, Claudia L.', 'Watthanaworawit, Wanitda', 'Carrara, Verena I.', 'Kapella, Bryan K.', 'Painter, John', 'Nosten, François H.']",Emerg Infect Dis,,,True
c26343b1cf5dfc83c01af64179530a7cfa69c5c8,PMC,"Rhinovirus Outbreaks in Long-term Care Facilities, Ontario, Canada",http://dx.doi.org/10.3201/eid1609.100476,PMC3294989,20735934,NO-CC CODE,"Diagnostic difficulties may have led to underestimation of rhinovirus infections in long-term care facilities. Using surveillance data, we found that rhinovirus caused 59% (174/297) of respiratory outbreaks in these facilities during 6 months in 2009. Disease was sometimes severe. Molecular diagnostic testing can differentiate these outbreaks from other infections such as influenza.",2010 Sep,"['Longtin, Jean', 'Marchand-Austin, Alex', 'Winter, Anne-Luise', 'Patel, Samir', 'Eshaghi, Alireza', 'Jamieson, Frances', 'Low, Donald E.', 'Gubbay, Jonathan B.']",Emerg Infect Dis,,,True
026195c31c1b5e03c8b24560de008bce009e6ada,PMC,Rapid Identification of Emerging Pathogens: Coronavirus,http://dx.doi.org/10.3201/eid1103.040629,PMC3298233,15757550,NO-CC CODE,"We describe a new approach for infectious disease surveillance that facilitates rapid identification of known and emerging pathogens. The process uses broad-range polymerase chain reaction (PCR) to amplify nucleic acid targets from large groupings of organisms, electrospray ionization mass spectrometry for accurate mass measurements of PCR products, and base composition signature analysis to identify organisms in a sample. We demonstrate this principle by using 14 isolates of 9 diverse Coronavirus spp., including the severe acute respiratory syndrome–associated coronavirus (SARS-CoV). We show that this method could identify and distinguish between SARS and other known CoV, including the human CoV 229E and OC43, individually and in a mixture of all 3 human viruses. The sensitivity of detection, measured by using titered SARS-CoV spiked into human serum, was ≈1 PFU/mL. This approach, applicable to the surveillance of bacterial, viral, fungal, or protozoal pathogens, is capable of automated analysis of >900 PCR reactions per day.",2005 Mar,"['Sampath, Rangarajan', 'Hofstadler, Steven A.', 'Blyn, Lawrence B.', 'Eshoo, Mark W.', 'Hall, Thomas A.', 'Massire, Christian', 'Levene, Harold M.', 'Hannis, James C.', 'Harrell, Patina M.', 'Neuman, Benjamin', 'Buchmeier, Michael J.', 'Jiang, Yun', 'Ranken, Raymond', 'Drader, Jared J.', 'Samant, Vivek', 'Griffey, Richard H.', 'McNeil, John A.', 'Crooke, Stanley T.', 'Ecker, David J.']",Emerg Infect Dis,,,True
2f3f3fc88a1b21cfb6c1e38e5cd61b856e6caab8,PMC,"SARS Risk Perceptions in Healthcare Workers, Japan",http://dx.doi.org/10.3201/eid1103.040631,PMC3298234,15757555,NO-CC CODE,"In coping with severe acute respiratory syndrome (SARS), infection control measures are a key aspect of protecting healthcare workers. We conducted a survey concerning perception of risk and countermeasures for SARS in 7 tertiary hospitals in Japan from July through September 2003, immediately after the SARS epidemic in neighboring countries. Based on 7,282 respondents out of 9,978 questionnaires administered, we found the perception of risk to be relatively high and the perception of countermeasures at the institutional level to be relatively low. Knowledge of preventive measures, concept of (opinions regarding) institutional measures, and perception of risk differed substantially among the 3 job categories, notably between physicians and nurses. The concept of institutional measures was the most important predictor of individual perception of risk. In view of the potential for future epidemics, planning and implementing institutional measures should be given a high priority.",2005 Mar,"['Imai, Teppei', 'Takahashi, Ken', 'Hoshuyama, Tsutomu', 'Hasegawa, Naoki', 'Lim, Meng-Kin', 'Koh, David']",Emerg Infect Dis,,,True
a66ada771ab0038a0b3dcd76cc3b3f9833416329,PMC,"SARS Risk Perceptions in Healthcare Workers, Japan",http://dx.doi.org/10.3201/eid1103.040631,PMC3298234,15757555,NO-CC CODE,"In coping with severe acute respiratory syndrome (SARS), infection control measures are a key aspect of protecting healthcare workers. We conducted a survey concerning perception of risk and countermeasures for SARS in 7 tertiary hospitals in Japan from July through September 2003, immediately after the SARS epidemic in neighboring countries. Based on 7,282 respondents out of 9,978 questionnaires administered, we found the perception of risk to be relatively high and the perception of countermeasures at the institutional level to be relatively low. Knowledge of preventive measures, concept of (opinions regarding) institutional measures, and perception of risk differed substantially among the 3 job categories, notably between physicians and nurses. The concept of institutional measures was the most important predictor of individual perception of risk. In view of the potential for future epidemics, planning and implementing institutional measures should be given a high priority.",2005 Mar,"['Imai, Teppei', 'Takahashi, Ken', 'Hoshuyama, Tsutomu', 'Hasegawa, Naoki', 'Lim, Meng-Kin', 'Koh, David']",Emerg Infect Dis,,,False
13b6abc1061e1cb04624b733ae472952f741e17f,PMC,Fever Screening at Airports and Imported Dengue,http://dx.doi.org/10.3201/eid1103.040420,PMC3298237,15757566,NO-CC CODE,"Airport fever screening in Taiwan, July 2003–June 2004, identified 40 confirmed dengue cases. Results obtained by capture immunoglobulin (Ig) M and IgG enzyme-linked immunoassay, real time 1-step polymerase chain reaction, and virus isolation showed that 33 (82.5%) of 40 patients were viremic. Airport fever screening can thus quickly identify imported dengue cases.",2005 Mar,"['Shu, Pei-Yun', 'Chien, Li-Jung', 'Chang, Shu-Fen', 'Su, Chien-Ling', 'Kuo, Yu-Chung', 'Liao, Tsai-Ling', 'Ho, Mei-Shang', 'Lin, Ting-Hsiang', 'Huang, Jyh-Hsiung']",Emerg Infect Dis,,,True
d40e933624cc2b3006d8998924d79e103cf06fe0,PMC,SARS-associated Coronavirus Transmitted from Human to Pig,http://dx.doi.org/10.3201/eid1103.040824,PMC3298239,15757562,NO-CC CODE,SEVERE ACUTE RESPIRATORY SYNDROME–ASSOCIATED: coronavirus (SARS-CoV) was isolated from a pig during a survey for possible routes of viral transmission after a SARS epidemic. Sequence and epidemiology analyses suggested that the pig was infected by a SARS-CoV of human origin.,2005 Mar,"['Chen, Weijun', 'Yan, Minghua', 'Yang, Ling', 'Ding, Boliang', 'He, Bo', 'Wang, Yingzhen', 'Liu, Xiuli', 'Liu, Chenhui', 'Zhu, Hui', 'You, Bo', 'Huang, Shengyong', 'Zhang, Jiangguo', 'Mu, Feng', 'Xiang, Zhao', 'Feng, Xiaoli', 'Wen, Jie', 'Fang, Jianqiu', 'Yu, Jun', 'Yang, Huanming', 'Wang, Jian']",Emerg Infect Dis,,,True
7d60e86e17b289ff581de119742058c51540d58b,PMC,Longitudinally Profiling Neutralizing Antibody Response to SARS Coronavirus with Pseudotypes,http://dx.doi.org/10.3201/eid1103.040906,PMC3298259,15757556,NO-CC CODE,The severe acute respiratory syndrome–associated coronavirus (SARS-CoV) spike protein (S) is a major target for neutralizing antibodies. Retroviral SARS-CoV S pseudotypes have been constructed and used to develop an in vitro microneutralization assay that is both sensitive and specific for SARS-CoV neutralizing antibodies. Neutralization titers measured by this assay are highly correlated to those measured by an assay using replication-competent SARS-CoV. No cross-neutralization occurred with human sera known to contain antibodies to coronavirus strains OC43 and 229E. The pseudotype assay was used to profile neutralizing antibody responses against SARS-CoV S in sequential serum samples taken from 41 confirmed SARS patients during the 2003 outbreak in Hong Kong and shows long-lasting immunity in most recovered patients. The pseudotype assay does not require handling live SARS virus; it is a useful tool to determine neutralizing titers during natural infection and the preclinical evaluation of candidate vaccines.,2005 Mar,"['Temperton, Nigel J.', 'Chan, Paul K.', 'Simmons, Graham', 'Zambon, Maria C.', 'Tedder, Richard S.', 'Takeuchi, Yasuhiro', 'Weiss, Robin A.']",Emerg Infect Dis,,,True
5e0a713a7436909c940dc70693cf666dd9c8ac62,PMC,SARS-related Perceptions in Hong Kong,http://dx.doi.org/10.3201/eid1103.040675,PMC3298267,15757557,NO-CC CODE,"To understand different aspects of community responses related to severe acute respiratory syndrome (SARS), 2 population-based, random telephone surveys were conducted in June 2003 and January 2004 in Hong Kong. More than 70% of respondents would avoid visiting hospitals or mainland China to avoid contracting SARS. Most respondents believed that SARS could be transmitted through droplets, fomites, sewage, and animals. More than 90% believed that public health measures were efficacious means of prevention; 40.4% believed that SARS would resurge in Hong Kong; and ≈70% would then wear masks in public places. High percentages of respondents felt helpless, horrified, and apprehensive because of SARS. Approximately 16% showed signs of posttraumatic symptoms, and ≈40% perceived increased stress in family or work settings. The general public in Hong Kong has been very vigilant about SARS but needs to be more psychologically prepared to face a resurgence of the epidemic.",2005 Mar,"['Lau, Joseph T.F.', 'Yang, Xilin', 'Pang, Ellie', 'Tsui, H.Y.', 'Wong, Eric', 'Wing, Yun Kwok']",Emerg Infect Dis,,,True
693eea7b0edb03ecf411992bc2f9df52bfbc020c,PMC,"The Dictionary of Virology, 4th Edition",http://dx.doi.org/10.3201/eid1608.100778,PMC3298299,,NO-CC CODE,,2010 Aug,"Brault, Aaron",Emerg Infect Dis,,,False
a750d0302fd2e1684bb414f2e81a1f5b4322da42,PMC,"Bat Coronaviruses and Experimental Infection of Bats, the Philippines",http://dx.doi.org/10.3201/eid1608.100208,PMC3298303,20678314,NO-CC CODE,"Fifty-two bats captured during July 2008 in the Philippines were tested by reverse transcription–PCR to detect bat coronavirus (CoV) RNA. The overall prevalence of virus RNA was 55.8%. We found 2 groups of sequences that belonged to group 1 (genus Alphacoronavirus) and group 2 (genus Betacoronavirus) CoVs. Phylogenetic analysis of the RNA-dependent RNA polymerase gene showed that groups 1 and 2 CoVs were similar to Bat-CoV/China/A515/2005 (95% nt sequence identity) and Bat-CoV/HKU9–1/China/2007 (83% identity), respectively. To propagate group 2 CoVs obtained from a lesser dog-faced fruit bat (Cynopterus brachyotis), we administered intestine samples orally to Leschenault rousette bats (Rousettus leschenaulti) maintained in our laboratory. After virus replication in the bats was confirmed, an additional passage of the virus was made in Leschenault rousette bats, and bat pathogenesis was investigated. Fruit bats infected with virus did not show clinical signs of infection.",2010 Aug,"['Watanabe, Shumpei', 'Masangkay, Joseph S.', 'Nagata, Noriyo', 'Morikawa, Shigeru', 'Mizutani, Tetsuya', 'Fukushi, Shuetsu', 'Alviola, Phillip', 'Omatsu, Tsutomu', 'Ueda, Naoya', 'Iha, Koichiro', 'Taniguchi, Satoshi', 'Fujii, Hikaru', 'Tsuda, Shumpei', 'Endoh, Maiko', 'Kato, Kentaro', 'Tohya, Yukinobu', 'Kyuwa, Shigeru', 'Yoshikawa, Yasuhiro', 'Akashi, Hiroomi']",Emerg Infect Dis,,,True
907f894adb65a78f0d4ee2b936c4637c0bbddcf3,PMC,"Viral Bacterial Artificial Chromosomes: Generation, Mutagenesis, and Removal of Mini-F Sequences",http://dx.doi.org/10.1155/2012/472537,PMC3303620,22496607,NO-CC CODE,"Maintenance and manipulation of large DNA and RNA virus genomes had presented an obstacle for virological research. BAC vectors provided a solution to both problems as they can harbor large DNA sequences and can efficiently be modified using well-established mutagenesis techniques in Escherichia coli. Numerous DNA virus genomes of herpesvirus and pox virus were cloned into mini-F vectors. In addition, several reverse genetic systems for RNA viruses such as members of Coronaviridae and Flaviviridae could be established based on BAC constructs. Transfection into susceptible eukaryotic cells of virus DNA cloned as a BAC allows reconstitution of recombinant viruses. In this paper, we provide an overview on the strategies that can be used for the generation of virus BAC vectors and also on systems that are currently available for various virus species. Furthermore, we address common mutagenesis techniques that allow modification of BACs from single-nucleotide substitutions to deletion of viral genes or insertion of foreign sequences. Finally, we review the reconstitution of viruses from BAC vectors and the removal of the bacterial sequences from the virus genome during this process.",2012 Feb 23,"['Tischer, B. Karsten', 'Kaufer, Benedikt B.']",J Biomed Biotechnol,,,True
9fe474e7623a88324431ac74e778e8403e263465,PMC,C-type lectin receptors and RIG-I-like receptors: new points on the oncogenomics map,http://dx.doi.org/10.2147/CMAR.S28983,PMC3304337,22427730,NO-CC CODE,"The group of pattern recognition receptors includes families of Toll-like receptors, NOD-like receptors, C-type lectin receptors, and RIG-I-like receptors. They are key sensors for a number of infectious agents, some of which are oncogenic, and they launch an immune response against them, normally promoting their eradication. Inherited variations in genes encoding these receptors and proteins and their signaling pathways may affect their function, possibly modulating cancer risk and features of cancer progression. There are numerous studies investigating the association of single nucleotide polymorphisms within or near genes encoding Toll-like receptors and NOD-like receptors, cancer risk, and features of cancer progression. However, there is an almost total absence of articles analyzing the correlation between polymorphisms of genes encoding C-type lectin receptors and RIG-I-like receptors and cancer risk or progression. Nevertheless, there is some evidence supporting the hypothesis that inherited C-type lectin receptor and RIG-I-like receptor variants can be associated with increased cancer risk. Certain C-type lectin receptors and RIG-I-like receptors recognize pathogen-associated molecular patterns of potentially oncogenic infectious agents, and certain polymorphisms of genes encoding C-type lectin receptors and RIG-I-like receptors may have functional consequences at the molecular level that can lead to association of such single nucleotide polymorphisms with risk or progression of some diseases that may modulate cancer risk, so these gene polymorphisms may affect cancer risk indirectly. Polymorphisms of genes encoding C-type lectin receptors and RIG-I-like receptors thereby may be correlated with a risk of lung, oral, esophageal, gastric, colorectal, and liver cancer, as well as nasopharyngeal carcinoma, glioblastoma, multiple myeloma, and lymphoma. The list of the most promising polymorphisms for oncogenomic investigations may include rs1926736, rs2478577, rs2437257, rs691005, rs2287886, rs735239, rs4804803, rs16910526, rs36055726, rs11795404, and rs10813831.",2012 Feb 24,"['Kutikhin, Anton G', 'Yuzhalin, Arseniy E']",Cancer Manag Res,,,True
1dbff143322886fdbdd833b8052ea3e3e0cc2d6d,PMC,"Serious Invasive Saffold Virus Infections in Children, 2009",http://dx.doi.org/10.3201/eid1801.110725,PMC3310106,22261113,NO-CC CODE,"The first human virus in the genus Cardiovirus was described in 2007 and named Saffold virus (SAFV). Cardioviruses can cause severe infections of the myocardium and central nervous system in animals, but SAFV has not yet been convincingly associated with disease in humans. To study a possible association between SAFV and infections in the human central nervous system, we designed a real-time PCR for SAFV and tested cerebrospinal fluid (CSF) samples from children <4 years of age. SAFV was detected in 2 children: in the CSF and a fecal sample from 1 child with monosymptomatic ataxia caused by cerebellitis; and in the CSF, blood, and myocardium of another child who died suddenly with no history of illness. Virus from each child was sequenced and shown to be SAFV type 2. These findings demonstrate that SAFV can cause serious invasive infection in children.",2012 Jan,"['Nielsen, Alex Christian Yde', 'Böttiger, Blenda', 'Banner, Jytte', 'Hoffmann, Thomas', 'Nielsen, Lars Peter']",Emerg Infect Dis,,,True
f5311986a1c067ce79c82fd9a50cc1b185718ff6,PMC,"Unexpected Result of Hendra Virus Outbreaks for Veterinarians, Queensland, Australia",http://dx.doi.org/10.3201/eid1801.111006,PMC3310112,22261152,NO-CC CODE,"A qualitative study of equine veterinarians and allied staff from Queensland, Australia, showed that veterinarians are ceasing equine practice because of fears related to Hendra virus. Their decisions were motivated by personal safety and legal liability concerns.",2012 Jan,"['Mendez, Diana H.', 'Judd, Jenni', 'Speare, Rick']",Emerg Infect Dis,,,True
8903fdfd69ea2f76dfde69fad78d73027fc59993,PMC,"Molecular Epidemiology of SARS-associated Coronavirus, Beijing",http://dx.doi.org/10.3201/eid1109.040773,PMC3310602,16229772,NO-CC CODE,"Single nucleotide variations (SNVs) at 5 loci (17564, 21721, 22222, 23823, and 27827) were used to define the molecular epidemiologic characteristics of severe acute respiratory syndrome–associated coronavirus (SARS-CoV) from Beijing patients. Five fragments targeted at the SNV loci were amplified directly from clinical samples by using reverse transcription–polymerase chain reaction (RT-PCR), before sequencing the amplified products. Analyses of 45 sequences obtained from 29 patients showed that the GGCTC motif dominated among samples collected from March to early April 2003; the TGTTT motif predominanted afterwards. The switch from GGCTC to TGTTT was observed among patients belonging to the same cluster, which ruled out the possibility of the coincidental superposition of 2 epidemics running in parallel in Beijing. The Beijing isolates underwent the same change pattern reported from Guangdong Province. The same series of mutations occurring in separate geographic locations and at different times suggests a dominant process of viral adaptation to the host.",2005 Sep,"['Liu, Wei', 'Tang, Fang', 'Fontanet, Arnaud', 'Zhan, Lin', 'Wang, Tian-Bao', 'Zhang, Pan-He', 'Luan, Yi-He', 'Cao, Chao-Yang', 'Zhao, Qiu-Min', 'Wu, Xiao-Ming', 'Xin, Zhong-Tao', 'Zuo, Shu-Qing', 'Baril, Laurence', 'Vabret, Astrid', 'Shao, Yi-Ming', 'Yang, Hong', 'Cao, Wu-Chun']",Emerg Infect Dis,,,True
2d102f7db396b4358f23cab728f3af3d8871c39c,PMC,Protective Behavior and West Nile Virus Risk,http://dx.doi.org/10.3201/eid1109.041184,PMC3310612,16229774,NO-CC CODE,"We conducted a cross-sectional, household survey in Oakville, Ontario, where an outbreak of West Nile virus (WNV) in 2002 led to an unprecedented number of cases of meningitis and encephalitis. Practicing >2 personal protective behavior traits reduced the risk for WNV infection by half.",2005 Sep,"['Loeb, Mark', 'Elliott, Susan J.', 'Gibson, Brian', 'Fearon, Margaret', 'Nosal, Robert', 'Drebot, Michael', ""D'Cuhna, Colin"", 'Harrington, Daniel', 'Smith, Stephanie', 'George, Pauline', 'Eyles, John']",Emerg Infect Dis,,,True
dc02bc5e86dabe370331b032a7956db8660db1cc,PMC,"Pandemic (H1N1) 2009 among Quarantined Close Contacts, Beijing, People’s Republic of China",http://dx.doi.org/10.3201/eid1710.101344,PMC3310645,22000351,NO-CC CODE,"We estimated the attack rate of pandemic (H1N1) 2009 and assessed risk factors for infection among close contacts quarantined in Beijing, People’s Republic of China. The first 613 confirmed cases detected between May 16 and September 15, 2009, were investigated; 7,099 close contacts were located and quarantined. The attack rate of confirmed infection in close contacts was 2.4% overall, ranging from 0.9% among aircraft passengers to >5% among household members. Risk factors for infection among close contacts were younger age, being a household member of an index case-patient, exposure during the index case-patient’s symptomatic phase, and longer exposure. Among close contacts with positive test results at the start of quarantine, 17.2% had subclinical infection. Having contact with a household member and younger age were the major risk factors for acquiring pandemic (H1N1) 2009 influenza virus infection. One person in 6 with confirmed pandemic (H1N1) 2009 was asymptomatic.",2011 Oct,"['Pang, Xinghuo', 'Yang, Peng', 'Li, Shuang', 'Zhang, Li', 'Tian, Lili', 'Li, Yang', 'Liu, Bo', 'Zhang, Yi', 'Liu, Baiwei', 'Huang, Ruogang', 'Li, Xinyu', 'Wang, Quanyi']",Emerg Infect Dis,,,True
74a6430d5021dafa50400460adc13f0e8ee4d457,PMC,Global Health Security in an Era of Global Health Threats,http://dx.doi.org/10.3201/eid1710.101656,PMC3310652,22000385,NO-CC CODE,,2011 Oct,"Cáceres, Sigfrido Burgos",Emerg Infect Dis,,,True
b703a12d98e44bc45d958bc7e15e38f570393e5c,PMC,"Human Cardioviruses, Meningitis, and Sudden Infant Death Syndrome in Children",http://dx.doi.org/10.3201/eid1712.111037,PMC3311172,22153118,NO-CC CODE,"Cardioviruses cause myocarditis and encephalomyelitis in rodents; human cardioviruses have not been ascribed to any disease. We screened 6,854 cerebrospinal fluid and 10 myocardium specimens from children and adults. A genotype 2 cardiovirus was detected from a child who died of sudden infant death syndrome, and 2 untypeable cardioviruses were detected from 2 children with meningitis.",2011 Dec,"['Drexler, Jan Felix', 'Baumgarte, Sigrid', 'Eschbach-Bludau, Monika', 'Simon, Arne', 'Kemen, Christoph', 'Bode, Udo', 'Eis-Hübinger, Anna-Maria', 'Madea, Burkhard', 'Drosten, Christian']",Emerg Infect Dis,,,True
c88784fa43f85c65f163931de7eb149e6e6dd8ba,PMC,"Knowledge of Avian Influenza (H5N1) among Poultry Workers, Hong Kong, China",http://dx.doi.org/10.3201/eid1712.110321,PMC3311183,22172127,NO-CC CODE,"In 2009, a cross-sectional survey of 360 poultry workers in Hong Kong, China, showed that workers had inadequate levels of avian influenza (H5N1) risk knowledge, preventive behavior, and outbreak preparedness. The main barriers to preventive practices were low perceived benefits and interference with work. Poultry workers require occupation-specific health promotion.",2011 Dec,"['Kim, Jean H.', 'Lo, Fung Kuk', 'Cheuk, Ka Kin', 'Kwong, Ming Sum', 'Goggins, William B.', 'Cai, Yan Shan', 'Lee, Shui Shan', 'Griffiths, Sian']",Emerg Infect Dis,,,True
736b7d64512deea08729df55af4d2aa0d1423cce,PMC,Astroviruses in Rabbits,http://dx.doi.org/10.3201/eid1712.110967,PMC3311190,22172457,NO-CC CODE,"By screening rabbits with enterocolitis or enteritis complex and asymptomatic rabbits, we identified a novel astrovirus. The virus was distantly related (19.3%–23.7% aa identity) in the capsid precursor to other mammalian astroviruses within the Mamastrovirus genus. By using real-time reverse transcription PCR, with specific primers and probes and targeting a conserved stretch in open reading frame 1b, we found rabbit astrovirus in 10 (43%) of 23 samples from animals with enteric disease and in 25 (18%) of 139 samples from asymptomatic animals in Italy during 2005–2008. The mean and median titers in the positive animals were 10(2)× and 10(3)× greater, respectively, in the symptomatic animals than in the asymptomatic animals. These findings support the idea that rabbit astroviruses should be included in the diagnostic algorithm of rabbit enteric disease and animal experiments to increase information obtained about their epidemiology and potential pathogenic role.",2011 Dec,"['Martella, Vito', 'Moschidou, Paschalina', 'Pinto, Pierfrancesco', 'Catella, Cristiana', 'Desario, Constantina', 'Larocca, Vittorio', 'Circella, Elena', 'Bànyai, Krisztian', 'Lavazza, Antonio', 'Magistrali, Chiara', 'Decaro, Nicola', 'Buonavoglia, Canio']",Emerg Infect Dis,,,True
6170c6d5c7e660f19226bfd026159c4ba6915fda,PMC,A Pilot Study of Host Genetic Variants Associated with Influenza-associated Deaths among Children and Young Adults,http://dx.doi.org/10.3201/eid1712.111002,PMC3311214,22172537,NO-CC CODE,"We compared the prevalence of 8 polymorphisms in the tumor necrosis factor and mannose-binding lectin genes among 105 children and young adults with fatal influenza with US population estimates and determined in subanalyses whether these polymorphisms were associated with sudden death and bacterial co-infection among persons with fatal influenza. No differences were observed in genotype prevalence or minor allele frequencies between persons with fatal influenza and the reference sample. Fatal cases with low-producing MBL2 genotypes had a 7-fold increased risk for invasive methicillin-resistant Staphylococcus aureus (MRSA) co-infection compared with fatal cases with high- and intermediate-producing MBL2 genotypes (odds ratio 7.1, 95% confidence interval 1.6–32.1). Limited analysis of 2 genes important to the innate immune response found no association between genetic variants and fatal influenza infection. Among children and young adults who died of influenza, low-producing MBL2 genotypes may have increased risk for MRSA co-infection.",2011 Dec,"['Ferdinands, Jill M.', 'Denison, Amy M.', 'Dowling, Nicole F.', 'Jost, Heather A.', 'Gwinn, Marta L.', 'Liu, Lindy', 'Zaki, Sherif R.', 'Shay, David K.']",Emerg Infect Dis,,,True
bbb2d7be584420074efdbaf24788af5c41b9d230,PMC,Lack of Association between CLEC5A Gene Single-Nucleotide Polymorphisms and Kawasaki Disease in Taiwanese Children,http://dx.doi.org/10.1155/2012/398628,PMC3318896,22536019,NO-CC CODE,"Background. Kawasaki disease is characterized by systemic vasculitis of unknown etiology. Previous genetic studies have identified certain candidate genes associated with susceptibility to KD and coronary artery lesions. Host innate immune response factors are involved in modulating the disease outcome. The aim of this study was to investigate CLEC5A (C-type lectin domain family 5) genetic polymorphisms with regards to the susceptibility and outcome of KD. Methods. A total of 1045 subjects (381 KD patients and 664 controls) were enrolled to identify 4 tagging single-nucleotide polymorphisms (tSNPs) of CLEC5A (rs1285968, rs11770855, rs1285935, rs1285933) by using the TaqMan Allelic Discrimination Assay. The Hardy-Weinberg equilibrium was assessed in cases and controls, and genetic effects were evaluated by the chi-square test. Results. No significant associations were noted between the genotypes and allele frequency of the 4 CLEC5A tSNPs between controls and patients. In the patients, polymorphisms of CLEC5A showed no significant association with coronary artery lesion formation and intravenous immunoglobulin treatment response. Conclusions. This study showed for the first time that polymorphisms of CLEC5A are not associated with susceptibility to KD, coronary artery lesion formation, and intravenous immunoglobulin treatment response in a Taiwanese population.",2012 Dec 22,"['Yang, Ya-Ling', 'Chang, Wei-Pin', 'Hsu, Yu-Wen', 'Chen, Wei-Chiao', 'Yu, Hong-Ren', 'Liang, Chi-Di', 'Tsai, Yao-Ting', 'Huang, Ying-Hsien', 'Yang, Kuender D.', 'Kuo, Ho-Chang', 'Chang, Wei-Chiao']",J Biomed Biotechnol,,,False
8ef3d0709843acf3358abcb4144c23478e817097,PMC,Lack of Association between CLEC5A Gene Single-Nucleotide Polymorphisms and Kawasaki Disease in Taiwanese Children,http://dx.doi.org/10.1155/2012/398628,PMC3318896,22536019,NO-CC CODE,"Background. Kawasaki disease is characterized by systemic vasculitis of unknown etiology. Previous genetic studies have identified certain candidate genes associated with susceptibility to KD and coronary artery lesions. Host innate immune response factors are involved in modulating the disease outcome. The aim of this study was to investigate CLEC5A (C-type lectin domain family 5) genetic polymorphisms with regards to the susceptibility and outcome of KD. Methods. A total of 1045 subjects (381 KD patients and 664 controls) were enrolled to identify 4 tagging single-nucleotide polymorphisms (tSNPs) of CLEC5A (rs1285968, rs11770855, rs1285935, rs1285933) by using the TaqMan Allelic Discrimination Assay. The Hardy-Weinberg equilibrium was assessed in cases and controls, and genetic effects were evaluated by the chi-square test. Results. No significant associations were noted between the genotypes and allele frequency of the 4 CLEC5A tSNPs between controls and patients. In the patients, polymorphisms of CLEC5A showed no significant association with coronary artery lesion formation and intravenous immunoglobulin treatment response. Conclusions. This study showed for the first time that polymorphisms of CLEC5A are not associated with susceptibility to KD, coronary artery lesion formation, and intravenous immunoglobulin treatment response in a Taiwanese population.",2012 Dec 22,"['Yang, Ya-Ling', 'Chang, Wei-Pin', 'Hsu, Yu-Wen', 'Chen, Wei-Chiao', 'Yu, Hong-Ren', 'Liang, Chi-Di', 'Tsai, Yao-Ting', 'Huang, Ying-Hsien', 'Yang, Kuender D.', 'Kuo, Ho-Chang', 'Chang, Wei-Chiao']",J Biomed Biotechnol,,,True
0faea8445e96457c63aa5ac80ed6b13b08c2e992,PMC,"Inpatient Capacity at Children’s Hospitals during Pandemic (H1N1) 2009 Outbreak, United States",http://dx.doi.org/10.3201/eid1709.101950,PMC3320222,21888795,NO-CC CODE,,2011 Sep,"['Sills, Marion R.', 'Hall, Matthew', 'Fieldston, Evan S.', 'Hain, Paul D.', 'Simon, Harold K.', 'Brogan, Thomas V.', 'Fagbuyi, Daniel B.', 'Mundorff, Michael B.', 'Shah, Samir S.']",Emerg Infect Dis,,,True
08c594ec305784d01af745c8a911525dcb45401a,PMC,"Inpatient Capacity at Children’s Hospitals during Pandemic (H1N1) 2009 Outbreak, United States",http://dx.doi.org/10.3201/eid1709.101950,PMC3320222,21888795,NO-CC CODE,,2011 Sep,"['Sills, Marion R.', 'Hall, Matthew', 'Fieldston, Evan S.', 'Hain, Paul D.', 'Simon, Harold K.', 'Brogan, Thomas V.', 'Fagbuyi, Daniel B.', 'Mundorff, Michael B.', 'Shah, Samir S.']",Emerg Infect Dis,,,False
6d4c75d6c089ec27a4e019c0ea659ab27662d163,PMC,Viral Loads in Clinical Specimens and SARS Manifestations,http://dx.doi.org/10.3201/eid1009.040058,PMC3320271,15498155,NO-CC CODE,"A retrospective viral load study was performed on clinical specimens from 154 patients with laboratory-confirmed severe acute respiratory syndrome (SARS); the specimens were prospectively collected during patients' illness. Viral load in nasopharyngeal aspirates (n = 142) from day 10 to day 15 after onset of symptoms was associated with oxygen desaturation, mechanical ventilation, diarrhea, hepatic dysfunction, and death. Serum viral load (n = 53) was associated with oxygen desaturation, mechanical ventilation, and death. Stool viral load (n = 94) was associated with diarrhea, and urine viral load (n = 111) was associated with abnormal urinalysis results. Viral replications at different sites are important in the pathogenesis of clinical and laboratory abnormalities of SARS.",2004 Sep,"['Hung, I.F.N.', 'Cheng, V.C.C.', 'Wu, A.K.L.', 'Tang, B.S.F.', 'Chan, K.H.', 'Chu, C.M.', 'Wong, M.M.L.', 'Hui, W.T.', 'Poon, L.L.M.', 'Tse, D.M.W.', 'Chan, K.S.', 'Woo, P.C.Y.', 'Lau, S.K.P.', 'Peiris, J.S.M.', 'Yuen, K.Y.']",Emerg Infect Dis,,,True
b45b6c2d890f204bd14f8140605ded987336b791,PMC,"SARS during Pregnancy, United States",http://dx.doi.org/10.3201/eid1009.040244,PMC3320293,15503406,NO-CC CODE,,2004 Sep,"['Stockman, Lauren J.', 'Lowther, Sara A.', 'Coy, Karen', 'Saw, Jenny', 'Parashar, Umesh D.']",Emerg Infect Dis,,,True
08339aa5e21ebd96be7ad261cbff35cc29466329,PMC,Ethics and Epidemics,http://dx.doi.org/10.3201/eid1009.040407,PMC3320297,,NO-CC CODE,,2004 Sep,"['Baker, Robert', 'Shelton, Wayne', 'Strosberg, Martin']",Emerg Infect Dis,,,True
70bc607ee56445c9b8a1786f1ba103318780d38c,PMC,Toronto Emergency Medical Services and SARS,http://dx.doi.org/10.3201/eid1009.040170,PMC3320298,15503405,NO-CC CODE,,2004 Sep,"['Silverman, Alexis', 'Simor, Andrew', 'Loutfy, Mona R.']",Emerg Infect Dis,,,False
f2e236f0458f86706985c627ef88d40c8f037492,PMC,SARS Antibody Test for Serosurveillance,http://dx.doi.org/10.3201/eid1009.040101,PMC3320307,15498156,NO-CC CODE,"A peptide-based enzyme-linked immunosorbent assay (ELISA) can be used for retrospective serosurveillance of severe acute respiratory syndrome (SARS) by helping identify undetected chains of disease transmission. The assay was developed by epitope mapping, using synthetic peptides from the spike, membrane, and nucleocapsid protein sequences of SARS-associated coronavirus. The new peptide ELISA consistently detected seroconversion by week 2 of onset of fever, and seropositivity remained through day 100. Specificity was 100% on normal blood donor samples, on serum samples associated with infection by other pathogens, and on an interference panel. The peptide-based test has advantages of safety, standardization, and automation over previous immunoassays for SARS. The assay was used for a retrospective survey of healthy healthcare workers in Taiwan who treated SARS patients. Asymptomatic seroconversions were detected in two hospitals that had nosocomial disease.",2004 Sep,"['Hsueh, Po-Ren', 'Kao, Chuan-Liang', 'Lee, Chun-Nan', 'Chen, Li-Kuan', 'Ho, Mei-Shang', 'Sia, Charles', 'De Fang, Xin', 'Lynn, Shugene', 'Chang, Tseng Yuan', 'Liu, Shi Kau', 'Walfield, Alan M.', 'Wang, Chang Yi']",Emerg Infect Dis,,,True
2381ff001bed1d5b7fef6c926fce1643c5089860,PMC,A Clinician's Dictionary of Pathogenic Microorganisms,http://dx.doi.org/10.3201/eid1009.040540,PMC3320314,,NO-CC CODE,,2004 Sep,"Raoult, Didier",Emerg Infect Dis,,,False
aa37211ba5110e94e0eb66faeab05d0e9a407c53,PMC,SARS-CoV Antibody Prevalence in All Hong Kong Patient Contacts,http://dx.doi.org/10.3201/eid1009.040155,PMC3320316,15498170,NO-CC CODE,"A total of 1,068 asymptomatic close contacts of patients with severe acute respiratory (SARS) from the 2003 epidemic in Hong Kong were serologically tested, and 2 (0.19%) were positive for SARS coronavirus immunoglobulin G antibody. SARS rarely manifests as a subclinical infection, and at present, wild animal species are the only important natural reservoirs of the virus.",2004 Sep,"['Leung, Gabriel M.', 'Chung, Pui-Hong', 'Tsang, Thomas', 'Lim, Wilina', 'Chan, Steve K.K.', 'Chau, Patsy', 'Donnelly, Christl A.', 'Ghani, Azra C.', 'Fraser, Christophe', 'Riley, Steven', 'Ferguson, Neil M.', 'Anderson, Roy M.', 'Law, Yuk-lung', 'Mok, Tina', 'Ng, Tonny', 'Fu, Alex', 'Leung, Pak-Yin', 'Peiris, J.S. Malik', 'Lam, Tai-Hing', 'Hedley, Anthony J.']",Emerg Infect Dis,,,True
6a4a0de0df03bfd7860d0732ea9d42daeac06b10,PMC,"Echovirus 30, Jiangsu Province, China",http://dx.doi.org/10.3201/eid1104.040995,PMC3320326,15829194,NO-CC CODE,"An outbreak of aseptic meningitis occurred in the northern area of Jiangsu Province in China from January to July in 2003. A total of 1,681 cases were involved in this outbreak, and 99% of patients were <15 years of age. To identify the etiologic agent, 66 cerebrospinal fluid specimens were tested by cell culture. Eighteen showed an enteroviruslike cytopathic effect on MRC-5 human fetal diploid lung cells. An enterovirus primer-mediated reverse transcriptase–polymerase chain reaction, a standard neutralization assay, and sequencing of the complete capsid-encoding (VP1) gene identified the 18 isolates (FDJS03) as echovirus 30. At least a 10% difference was seen in nucleotide sequences of VP1 between FDJS03 isolates and other global strains of echovirus 30. Phylogenetic analysis based on complete sequences of VP1 was performed to further characterize the FDJS03 isolates. This report is the first to identify a distinct lineage of echovirus 30 as a probable cause of this outbreak.",2005 Apr,"['Zhao, Ya Nan', 'Jiang, Qing Wu', 'Jiang, Ren Jie', 'Chen, Liang', 'Perlin, David S.']",Emerg Infect Dis,,,True
89860bed01edcabbb95ae9ea724e7f60feac25da,PMC,"SARS Risk Perception and Preventive Measures, Singapore and Japan",http://dx.doi.org/10.3201/eid1104.040765,PMC3320330,15834989,NO-CC CODE,,2005 Apr,"['Koh, David', 'Takahashi, Ken', 'Lim, Meng-Kin', 'Imai, Teppei', 'Chia, Sin-Eng', 'Qian, Feng', 'Ng, Vivian', 'Fones, Calvin']",Emerg Infect Dis,,,True
63f7049d200896290b38b38711113054f7ea1b50,PMC,Emerging Infectious Diseases: a 10-Year Perspective from the National Institute of Allergy and Infectious Diseases,http://dx.doi.org/10.3201/eid1104.041167,PMC3320336,15829188,NO-CC CODE,"Although optimists once imagined that serious infectious disease threats would by now be conquered, newly emerging (e.g., severe acute respiratory syndrome [SARS]), reemerging (e.g., West Nile virus), and even deliberately disseminated infectious diseases (e.g., anthrax bioterrorism) continue to appear throughout the world. Over the past decade, the global effort to identify and characterize infectious agents, decipher the underlying pathways by which they cause disease, and develop preventive measures and treatments for many of the world's most dangerous pathogens has resulted in considerable progress. Intramural and extramural investigators supported by the National Institute of Allergy and Infectious Diseases (NIAID) have contributed substantially to this effort. This overview highlights selected NIAID-sponsored research advances over the past decade, with a focus on progress in combating HIV/AIDS, malaria, tuberculosis, influenza, SARS, West Nile virus, and potential bioterror agents. Many basic research discoveries have been translated into novel diagnostics, antiviral and antimicrobial compounds, and vaccines, often with extraordinary speed.",2005 Apr,"['Fauci, Anthony S.', 'Touchette, Nancy A.', 'Folkers, Gregory K.']",Emerg Infect Dis,,,True
2132357512ad6873036487fb997bba2a600fd554,PMC,Web-based Investigation of Multistate Salmonellosis Outbreak,http://dx.doi.org/10.3201/eid1104.040997,PMC3320341,15829202,NO-CC CODE,"We investigated a large outbreak of Salmonella enterica serotype Javiana among attendees of the 2002 U.S. Transplant Games, including 1,500 organ transplant recipients. Web-based survey methods identified pre-diced tomatoes as the source of this outbreak, which highlights the utility of such investigative tools to cope with the changing epidemiology of foodborne diseases.",2005 Apr,"['Srikantiah, Padmini', 'Bodager, Dean', 'Toth, Bill', 'Kass-Hout, Taha', 'Hammond, Roberta', 'Stenzel, Sara', 'Hoekstra, R.M.', 'Adams, Jennifer', 'Van Duyne, Susan', 'Mead, Paul S.']",Emerg Infect Dis,,,True
27cf8042e0891da58b8c21c382a78efdb76110bc,PMC,Are SARS Superspreaders Cloud Adults?,http://dx.doi.org/10.3201/eid1104.040639,PMC3320342,15834986,NO-CC CODE,,2005 Apr,"['Bassetti, Stefano', 'Bischoff, Werner E.', 'Sherertz, Robert J.']",Emerg Infect Dis,,,True
6edb6aecb92419c8aa964cecabc115e732f85344,PMC,Patient Contact Recall after SARS Exposure,http://dx.doi.org/10.3201/eid1104.040648,PMC3320347,15829207,NO-CC CODE,We reinterviewed healthcare workers who had been exposed to a patient with severe acute respiratory syndrome (SARS) in an intensive care unit to evaluate the effect of time on recall reliability and willingness to report contact activities and infection control precautions. Healthcare workers reliably recalled events 6 months after exposure.,2005 Apr,"['Dimoulas, Popy', 'Green, Karen A.', 'Shigayeva, Altynay', 'Aquino, Michael', 'McGeer, Allison', 'Scales, Damon C.', None]",Emerg Infect Dis,,,True
9dfa774c9dee1273ae85f5c7199e83bbb45eb18b,PMC,Media Effects on Students during SARS Outbreak,http://dx.doi.org/10.3201/eid1105.040512,PMC3320361,15890131,NO-CC CODE,"A few months after the 2003 severe acute respiratory syndrome (SARS) outbreak, a sample of Canadian undergraduate university students completed a questionnaire that showed that, despite believing media coverage of the outbreak was excessive, they had little anxiety about acquiring SARS. Additionally, 69% of participants failed a SARS-specific knowledge section of the questionnaire.",2005 May,"['Bergeron, Sheri L.', 'Sanchez, Ana L.']",Emerg Infect Dis,,,True
ed276d222dcdee71e13c0b46fdb9c70f06d5fcd9,PMC,"Avian Influenza Risk Perception, Hong Kong",http://dx.doi.org/10.3201/eid1105.041225,PMC3320362,15890118,NO-CC CODE,"A telephone survey of 986 Hong Kong households determined exposure and risk perception of avian influenza from live chicken sales. Householders bought 38,370,000 live chickens; 11% touched them when buying, generating 4,220,000 exposures annually; 36% (95% confidence interval [CI] 33%–39%) perceived this as risky, 9% (7%–11%) estimated >50% likelihood of resultant sickness, whereas 46% (43%–49%) said friends worried about such sickness. Recent China travel (adjusted odds ratio 0.35; CI 0.13–0.91), traditional beliefs (1.20, 1.06–1.13), willingness to change (0.29, 0.11–0.81) and believing cooking protects against avian influenza (8.66, 1.61-46.68) predicted buying. Birth in China (2.79, 1.43–5.44) or overseas (4.23, 1.43–12.53) and unemployment (3.87, 1.24–12.07) predicted touching. Age, avian influenza contagion worries, husbandry threat, avian influenza threat, and avian influenza anxiety predicted perceived sickness risk. High population exposures to live chickens and low perceived risk are potentially important health threats in avian influenza.",2005 May,"['Fielding, Richard', 'Lam, Wendy W.T.', 'Ho, Ella Y.Y.', 'Lam, Tai Hing', 'Hedley, Anthony J.', 'Leung, Gabriel M.']",Emerg Infect Dis,,,True
7e71b0b68479d59fe662f53a7ba3e6037b7e09a2,PMC,SARS Alert Applicability,http://dx.doi.org/10.3201/eid1008.040221,PMC3320393,15503403,NO-CC CODE,,2004 Aug,,Emerg Infect Dis,,,True
831eced9e695618368c334b5b42159f2172fbe55,PMC,"SARS Risk Perception, Knowledge, Precautions, and Information Sources, the Netherlands",http://dx.doi.org/10.3201/eid1008.040283,PMC3320399,15496256,NO-CC CODE,"Severe acute respiratory syndrome (SARS)–related risk perceptions, knowledge, precautionary actions, and information sources were studied in the Netherlands during the 2003 SARS outbreak. Although respondents were highly aware of the SARS outbreak, the outbreak did not result in unnecessary precautionary actions or fears.",2004 Aug,"['Brug, Johannes', 'Aro, Arja R.', 'Oenema, Anke', 'de Zwart, Onno', 'Richardus, Jan Hendrik', 'Bishop, George D.']",Emerg Infect Dis,,,True
c9877ae6ac5465d45291db9429e8e2b0976c8c48,PMC,SARS Transmission and Commercial Aircraft,http://dx.doi.org/10.3201/eid1008.040093,PMC3320400,15503396,NO-CC CODE,,2004 Aug,"['Breugelmans, J. Gabrielle', 'Zucs, Phillip', 'Porten, Klaudia', 'Broll, Susanne', 'Niedrig, Matthias', 'Ammon, Andrea', 'Krause, Gérard']",Emerg Infect Dis,,,True
90a0b231586bf8d6f53f07088f37a73ffe2ffe48,PMC,"SARS in Three Categories of Hospital Workers, Hong Kong",http://dx.doi.org/10.3201/eid1008.040041,PMC3320402,15496240,NO-CC CODE,"We analyzed attack rates for severe acute respiratory syndrome (SARS) in three categories of hospital workers (nurses, nonmedical support staff, and other technical or medical staff) in all public hospitals in Hong Kong that had admitted SARS patients. Of 16 such hospitals, 14 had cases. The overall attack rate was 1.20%. Nonmedical support staff had the highest attack rate (2.73%). The odds ratios of group nonmedical support staff versus those of nurses and of nonmedical support staff versus other technical or medical staff were 2.30 (p < 0.001) and 9.78 (p < 0.001), respectively. The number of affected staff and attack rates were significantly correlated with the number of SARS patients admitted (r = 0.914 and 0.686, respectively). Affected patients were concentrated in three hospitals and in the earlier phase of the epidemic. Cleaning and clerical staff on hospital wards were at a much higher risk.",2004 Aug,"['Lau, Joseph T.F.', 'Yang, Xilin', 'Leung, Ping-Chung', 'Chan, Louis', 'Wong, Eliza', 'Fong, Carmen', 'Tsui, Hi-Yi']",Emerg Infect Dis,,,True
ab50cf0159a56f447825137b6100ce061f2a745a,PMC,Print Media Response to SARS in New Zealand,http://dx.doi.org/10.3201/eid1008.031096,PMC3320422,15496249,NO-CC CODE,"To examine the media response to severe acute respiratory syndrome, we reviewed New Zealand's major newspaper (261 articles for 3 months). While important accurate health messages were frequently included, some were missed (e.g., hand washing in only 2% of articles). No incorrect information was identified, and health spokespersons were accurately quoted.",2004 Aug,"['Wilson, Nick', 'Thomson, George', 'Mansoor, Osman']",Emerg Infect Dis,,,True
eaca17432584c7f2ecbb17e611df70deed0dbec3,PMC,Managing Febrile Respiratory Illnesses during a Hypothetical SARS Outbreak,http://dx.doi.org/10.3201/eid1102.040524,PMC3320437,15752435,NO-CC CODE,"Since the World Health Organization declared the global outbreak of severe acute respiratory syndrome (SARS) contained in July 2003, new cases have periodically reemerged in Asia. This situation has placed hospitals and health officials worldwide on heightened alert. In a future outbreak, rapidly and accurately distinguishing SARS from other common febrile respiratory illnesses (FRIs) could be difficult. We constructed a decision-analysis model to identify the most efficient strategies for managing undifferentiated FRIs within a hypothetical SARS outbreak in New York City during the season of respiratory infections. If establishing reliable epidemiologic links were not possible, societal costs would exceed $2.0 billion per month. SARS testing with existing polymerase chain reaction assays would have harmful public health and economic consequences if SARS made up <0.1% of circulating FRIs. Increasing influenza vaccination rates among the general population before the onset of respiratory season would save both money and lives.",2005 Feb,"['Khan, Kamran', 'Muennig, Peter', 'Gardam, Michael', 'Zivin, Joshua Graff']",Emerg Infect Dis,,,True
1c5dca0eea0fa4b2ae7f523c8b8b076e56fd623f,PMC,Diagnostic System for Rapid and Sensitive Differential Detection of Pathogens,http://dx.doi.org/10.3201/eid1102.040492,PMC3320438,15752453,NO-CC CODE,"Naturally emerging and deliberately released pathogens demand new detection strategies to allow early recognition and containment. We describe a diagnostic system for rapid, sensitive, multiplex discrimination of microbial gene sequences and report its application for detecting 22 respiratory pathogens in clinical samples.",2005 Feb,"['Briese, Thomas', 'Palacios, Gustavo', 'Kokoris, Mark', 'Jabado, Omar', 'Liu, Zhiqiang', 'Renwick, Neil', 'Kapoor, Vishal', 'Casas, Inmaculada', 'Pozo, Francisco', 'Limberger, Ron', 'Perez-Brena, Pilar', 'Ju, Jingyue', 'Lipkin, W. Ian']",Emerg Infect Dis,,,True
1bc6ca895dc8218ab2d2a126ae92b1593637328c,PMC,"Quarantine for SARS, Taiwan",http://dx.doi.org/10.3201/eid1102.040190,PMC3320446,15752447,NO-CC CODE,"During the 2003 outbreak of severe acute respiratory syndrome (SARS) in Taiwan, >150,000 persons were quarantined, 24 of whom were later found to have laboratory-confirmed SARS-coronavirus (SARS-CoV) infection. Since no evidence exists that SARS-CoV is infective before the onset of symptoms and the quarantined persons were exposed but not symptomatic, we thought the quarantine's effectiveness should be investigated. Using the Taiwan quarantine data, we found that the onset-to-diagnosis time of previously quarantined confirmed case-patients was significantly shortened compared to that for those who had not been quarantined. Thus, quarantine for SARS in Taiwan screened potentially infective persons for swift diagnosis and hospitalization after onset, thereby indirectly reducing infections. Full-scale quarantine measures implemented on April 28 led to a significant improvement in onset-to-diagnosis time of all SARS patients, regardless of previous quarantine status. We discuss the temporal effects of quarantine measures and other interventions on detection and isolation as well as the potential usefulness of quarantine in faster identification of persons with SARS and in improving isolation measures.",2005 Feb,"['Hsieh, Ying-Hen', 'King, Chwan-Chuan', 'Chen, Cathy W. S.', 'Ho, Mei-Shang', 'Lee, Jen-Yu', 'Liu, Feng-Chi', 'Wu, Yi-Chun', None]",Emerg Infect Dis,,,True
6d7851259dcf3f3a78c8f34b7784b07d2cd65296,PMC,"SARS Control and Psychological Effects of Quarantine, Toronto, Canada",http://dx.doi.org/10.3201/eid1102.040760,PMC3320456,15759346,NO-CC CODE,,2005 Feb,"Hull, Harry F.",Emerg Infect Dis,,,True
156e1cb11da156eec419079bd54c3b78ab65d6f7,PMC,"Late Recognition of SARS in Nosocomial Outbreak, Toronto",http://dx.doi.org/10.3201/eid1102.040607,PMC3320463,15752456,NO-CC CODE,"Late recognition of severe acute respiratory syndrome (SARS) was associated with no known SARS contact, hospitalization before the nosocomial outbreak was recognized, symptom onset while hospitalized, wards with SARS clusters, and postoperative status. SARS is difficult to recognize in hospitalized patients with a variety of underlying conditions in the absence of epidemiologic links.",2005 Feb,"['Wong, Thomas', 'Wallington, Tamara', 'McDonald, L. Clifford', 'Abbas, Zahid', 'Christian, Michael', 'Low, Donald E.', 'Gravel, Denise', 'Ofner, Marianna', 'Mederski, Barbara', 'Berger, Lisa', 'Hansen, Lisa', 'Harrison, Cheryl', 'King, Arlene', 'Yaffe, Barbara', 'Tam, Theresa']",Emerg Infect Dis,,,True
5aea42c8922c84b19c8ae83793d535d53667a772,PMC,Posttraumatic Stress after SARS,http://dx.doi.org/10.3201/eid1108.041083,PMC3320475,16102324,NO-CC CODE,"Posttraumatic stress disorder (PTSD) can arise in patients with medical illness. We used 2 Chinese self-report measures to examine features of PTSD, anxiety, and depression in 131 survivors of severe acute respiratory syndrome at 1 month and 3 months after discharge from the hospital. Risk factors associated with psychological distress were identified.",2005 Aug,"['Wu, Kitty K.', 'Chan, Sumee K.', 'Ma, Tracy M.']",Emerg Infect Dis,,,True
54c1ec13d3697c96a018ad42935295c9d0aefa55,PMC,Modeling Control Strategies of Respiratory Pathogens,http://dx.doi.org/10.3201/eid1108.040449,PMC3320482,16102315,NO-CC CODE,"Effectively controlling infectious diseases requires quantitative comparisons of quarantine, infection control precautions, case identification and isolation, and immunization interventions. We used contact network epidemiology to predict the effect of various control policies for a mildly contagious disease, such as severe acute respiratory syndrome, and a moderately contagious disease, such as smallpox. The success of an intervention depends on the transmissibility of the disease and the contact pattern between persons within a community. The model predicts that use of face masks and general vaccination will only moderately affect the spread of mildly contagious diseases. In contrast, quarantine and ring vaccination can prevent the spread of a wide spectrum of diseases. Contact network epidemiology can provide valuable quantitative input to public health decisionmaking, even before a pathogen is well characterized.",2005 Aug,"['Pourbohloul, Babak', 'Meyers, Lauren Ancel', 'Skowronski, Danuta M.', 'Krajden, Mel', 'Patrick, David M.', 'Brunham, Robert C.']",Emerg Infect Dis,,,True
687d11c75e96fdb573a27b6ac0ec3802de6de48a,PMC,Cost-Benefit of Stockpiling Drugs for Influenza Pandemic,http://dx.doi.org/10.3201/eid1108.041156,PMC3320484,16102319,NO-CC CODE,"We analyzed strategies for the use of stockpiled antiviral drugs in the context of a future influenza pandemic and estimated cost-benefit ratios. Current stockpiling of oseltamivir appears to be cost-saving to the economy under several treatment strategies, including therapeutic treatment of patients and postexposure prophylactic treatment of patients' close contacts.",2005 Aug,"['Balicer, Ran D.', 'Huerta, Michael', 'Davidovitch, Nadav', 'Grotto, Itamar']",Emerg Infect Dis,,,True
ffb381668d93248759ca3855425e05722cb9f562,PMC,"Human Coronavirus NL63, France",http://dx.doi.org/10.3201/eid1108.050110,PMC3320486,16102311,NO-CC CODE,"The human coronavirus NL63 (HCoV-NL63) was first identified in the Netherlands, and its circulation in France has not been investigated. We studied HCoV-NL63 infection in hospitalized children diagnosed with respiratory tract infections. From November 2002 to April 2003, we evaluated 300 respiratory specimens for HCoV-NL63. Of the 300 samples, 28 (9.3%) were positive for HCoV-NL63. The highest prevalence was found in February (18%). The main symptoms were fever (61%), rhinitis (39%), bronchiolitis (39%), digestive problems (33%), otitis (28%), pharyngitis (22%), and conjunctivitis (17%). A fragment of the spike protein gene was sequenced to determine the variety of circulating HCoV-NL63. Phylogenetic analysis indicated that strains with different genetic markers cocirculate in France.",2005 Aug,"['Vabret, Astrid', 'Mourez, Thomas', 'Dina, Julia', 'van der Hoek, Lia', 'Gouarin, Stéphanie', 'Petitjean, Joëlle', 'Brouard, Jacques', 'Freymuth, François']",Emerg Infect Dis,,,True
9e04e344099e9f7ae40628aba46e4a2cf65aa876,PMC,SARS Vaccine Protective in Mice,http://dx.doi.org/10.3201/eid1108.041003,PMC3320494,16110580,NO-CC CODE,,2005 Aug,"['Stadler, Konrad', 'Roberts, Anjeanette', 'Becker, Stephan', 'Vogel, Leatrice', 'Eickmann, Markus', 'Kolesnikova, Larissa', 'Klenk, Hans-Dieter', 'Murphy, Brian', 'Rappuoli, Rino', 'Abrignani, Sergio', 'Subbarao, Kanta']",Emerg Infect Dis,,,True
a9ef59df236cebc1284670d073d8724ca360ac6a,PMC,"Yersinia Species Isolated from Bats, Germany",http://dx.doi.org/10.3201/eid1603.091035,PMC3322022,20202457,NO-CC CODE,,2010 Mar,"['Mühldorfer, Kristin', 'Wibbelt, Gudrun', 'Haensel, Joachim', 'Riehm, Julia', 'Speck, Stephanie']",Emerg Infect Dis,,,True
fbac14ed1b86f5accd35d9a3153591b938b7d72d,PMC,"Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus, Asia",http://dx.doi.org/10.3201/eid1709.110411,PMC3322091,21888830,NO-CC CODE,,2011 Sep,"['An, Tong-Qing', 'Tian, Zhi-Jun', 'Leng, Chao-Liang', 'Peng, Jin-Mei', 'Tong, Guang-Zhi']",Emerg Infect Dis,,,True
fbcbe40a6873d2dabd90963c5a7c8e26531eb52f,PMC,Severe Acute Respiratory Syndrome–associated Coronavirus in Lung Tissue,http://dx.doi.org/10.3201/eid1001.030404,PMC3322746,15078592,NO-CC CODE,"Efforts to contain severe acute respiratory syndrome (SARS) have been limited by the lack of a standardized, sensitive, and specific test for SARS-associated coronavirus (CoV). We used a standardized reverse transcription-polymerase chain reaction assay to detect SARS-CoV in lung samples obtained from well-characterized patients who died of SARS and from those who died of other reasons. SARS-CoV was detected in all 22 postmortem lung tissues (to 10(9) viral copies/g) from 11 patients with probable SARS but was not detected in any of the 23 lung control samples (sample analysis was blinded). The sensitivity and specificity (95% confidence interval) were 100% (84.6% to 100%) and 100% (85.1% to 100%), respectively. Viral loads were significantly associated with a shorter course of illness but not with the use of ribavirin or steroids. CoV was consistently identified in the lungs of all patients who died of SARS but not in control patients, supporting a primary role for CoV in deaths.",2004 Jan,"['Mazzulli, Tony', 'Farcas, Gabriella A.', 'Poutanen, Susan M.', 'Willey, Barbara M.', 'Low, Donald E.', 'Butany, Jagdish', 'Asa, Sylvia L.', 'Kain, Kevin C.']",Emerg Infect Dis,,,True
e1a92eaaadeb57ad1273b68900ab659a34e1db12,PMC,"Virus Taxonomy: One Step Forward, Two Steps Back",http://dx.doi.org/10.3201/eid1001.030945,PMC3322753,15112667,NO-CC CODE,,2004 Jan,"Eberhard, Mark",Emerg Infect Dis,,,True
ab10fed7d8688da4c396efac79aa05d8d6b8f300,PMC,Immunofluorescence Assay for Serologic Diagnosis of SARS,http://dx.doi.org/10.3201/eid1003.030493,PMC3322771,15109430,NO-CC CODE,We evaluated a virus-infected cell-based indirect immunofluorescence assay for detecting anti–severe acute respiratory syndrome-associated coronavirus (SARS-CoV) immunoglobulin (Ig) G antibody. All confirmed SARS cases demonstrated seroconversion or fourfold rise in IgG antibody titer; no control was positive. Sensitivity and specificity of this assay were both 100%. Immunofluorescence assay can ascertain the status of SARS-CoV infection.,2004 Mar,"['Chan, Paul K. S.', 'Ng, King-Cheung', 'Chan, Rickjason C. W.', 'Lam, Rebecca K. Y.', 'Chow, Viola C. Y.', 'Hui, Mamie', 'Wu, Alan', 'Lee, Nelson', 'Yap, Florence H.Y.', 'Cheng, Frankie W. T.', 'Sung, Joseph J. Y.', 'Tam, John S.']",Emerg Infect Dis,,,True
e269ac6cbd3208b8f71892f9e1f8b9ccb225f472,PMC,Human Metapneumovirus-associated Atypical Pneumonia and SARS,http://dx.doi.org/10.3201/eid1003.030513,PMC3322781,15109421,NO-CC CODE,"Acute pneumonia developed in a previously healthy man during the outbreak of severe acute respiratory syndrome (SARS) in southern China in March 2003. Antibiotic treatment was ineffective, and he died 8 days after illness onset. Human metapneumovirus was isolated from lung tissue. No other pathogen was found. Other etiologic agents should thus be sought in apparent SARS cases when coronavirus infection cannot be confirmed.",2004 Mar,"['Chan, Paul K.S.', 'To, Ka-Fai', 'Wu, Alan', 'Tse, Gary M.K.', 'Chan, Kui-Fat', 'Lui, Siu-Fai', 'Sung, Joseph J.Y.', 'Tam, John S.', 'Tomlinson, Brian']",Emerg Infect Dis,,,True
f7d1b521f0668811e2435b60cce4657ff769f457,PMC,Early Defervescence and SARS Recovery,http://dx.doi.org/10.3201/eid1003.030500,PMC3322783,15116707,NO-CC CODE,,2004 Mar,"['Wang, Jann-Tay', 'Wang, Jiun-Ling', 'Fang, Chi-Tai', 'Chang, Shan-Chwen']",Emerg Infect Dis,,,True
d1501d93b454fa850a635ceed555f5266bc1db6a,PMC,SARS Transmission and Hospital Containment,http://dx.doi.org/10.3201/eid1003.030650,PMC3322797,15109403,NO-CC CODE,"An outbreak of severe acute respiratory syndrome (SARS) was detected in Singapore at the beginning of March 2003. The outbreak, initiated by a traveler to Hong Kong in late February 2003, led to sequential spread of SARS to three major acute care hospitals in Singapore. The critical factor in containing this outbreak was early detection and complete assessment of movements and follow-up of patients, healthcare workers, and visitors who were contacts. Visitor records were important in helping identify exposed persons who could carry the infection into the community. In the three hospital outbreaks, three different containment strategies were used to contain spread of infection: closing an entire hospital, removing all potentially infected persons to a dedicated SARS hospital, and managing exposed persons in place. On the basis of this experience, if a nosocomial outbreak is detected late, a hospital may need to be closed in order to contain spread of the disease. Outbreaks detected early can be managed by either removing all exposed persons to a designated location or isolating and managing them in place.",2004 Mar,"['Gopalakrishna, Gowri', 'Choo, Philip', 'Leo, Yee Sin', 'Tay, Boon Keng', 'Lim, Yean Teng', 'Khan, Ali S.', 'Tan, Chorh Chuan']",Emerg Infect Dis,,,True
ca18e923f1cd6532ba1a7f05ca8e2abfa940834a,PMC,Clinical Trials and Novel Pathogens: Lessons Learned from SARS,http://dx.doi.org/10.3201/eid1003.030702,PMC3322802,15109402,NO-CC CODE,"During the recent global outbreak of severe acute respiratory syndrome (SARS), thousands of patients received treatments of uncertain efficacy and known toxicity such as ribavirin and corticosteroids. Despite this, no controlled clinical trials assessing the efficacy of these agents were conducted. If a second global SARS outbreak occurred, clinicians would not have controlled data on which to base therapeutic decisions. We discuss the unique methodologic and logistical challenges faced by researchers who attempt to conduct controlled trials of therapeutic agents during an outbreak of a novel or unknown infectious pathogen. We draw upon our own experience in attempting to conduct a randomized controlled trial (trial) of ribavirin therapy for SARS and discuss the lessons learned. Strategies to facilitate future clinical trials during outbreaks of unknown or novel pathogens are also presented.",2004 Mar,"['Muller, Matthew P.', 'McGeer, Allison', 'Straus, Sharon E.', 'Hawryluck, Laura', 'Gold, Wayne L.']",Emerg Infect Dis,,,True
d8a0a04161c4ee9b42ffddb705b21ab539098447,PMC,Coronaviridae and SARS-associated Coronavirus Strain HSR1,http://dx.doi.org/10.3201/eid1003.030683,PMC3322807,15109406,NO-CC CODE,"During the recent severe acute respiratory (SARS) outbreak, the etiologic agent was identified as a new coronavirus (CoV). We have isolated a SARS-associated CoV (SARS-CoV) strain by injecting Vero cells with a sputum specimen from an Italian patient affected by a severe pneumonia; the patient traveled from Vietnam to Italy in March 2003. Ultrastructural analysis of infected Vero cells showed the virions within cell vesicles and around the cell membrane. The full-length viral genome sequence was similar to those derived from the Hong-Kong Hotel M isolate. By using both real-time reverse transcription–polymerase chain reaction TaqMan assay and an infectivity plaque assay, we determined that approximately 360 viral genomes were required to generate a PFU. In addition, heparin (100 μg/mL) inhibited infection of Vero cells by 50%. Overall, the molecular and biologic characteristics of the strain HSR1 provide evidence that SARS-CoV forms a fourth genetic coronavirus group with distinct genomic and biologic features.",2004 Mar,"['Vicenzi, Elisa', 'Canducci, Filippo', 'Pinna, Debora', 'Mancini, Nicasio', 'Carletti, Silvia', 'Lazzarin, Adriano', 'Bordignon, Claudio', 'Poli, Guido', 'Clementi, Massimo']",Emerg Infect Dis,,,True
8baba2afe8dd478ae1d7ed13b666098aa3bfb623,PMC,SARS and Pregnancy: A Case Report,http://dx.doi.org/10.3201/eid1002.030736,PMC3322896,15030710,NO-CC CODE,"We report a laboratory-confirmed case of severe acute respiratory syndrome (SARS) in a pregnant woman. Although the patient had respiratory failure, a healthy infant was subsequently delivered, and the mother is now well. There was no evidence of viral shedding at delivery. Antibodies to SARS virus were detected in cord blood and breast milk.",2004 Feb,"['Robertson, Corwin A.', 'Lowther, Sara A.', 'Birch, Thomas', 'Tan, Christina', 'Sorhage, Faye', 'Stockman, Lauren', 'McDonald, L. Clifford', 'Lingappa, Jairam R.', 'Bresnitz, Eddy']",Emerg Infect Dis,,,True
1dc89329e8a644d5dc0e2b0b845e65cbe17a782a,PMC,HHS/CDC Legal Response to SARS Outbreak,http://dx.doi.org/10.3201/eid1002.030721,PMC3322897,15030712,NO-CC CODE,"Before the severe acute respiratory syndrome (SARS) outbreak, the Centers for Disease Control and Prevention’s (CDC) legal authority to apprehend, detain, or conditionally release persons was limited to seven listed diseases, not including SARS, and could only be changed using a two-step process: 1) executive order of the President of the United States on recommendation by the Secretary, U.S. Department of Health and Human Services (HHS), and 2) amendment to CDC quarantine regulations (42 CFR Parts 70 and 71). In April 2003, in response to the SARS outbreak, the federal executive branch acted rapidly to add SARS to the list of quarantinable communicable diseases. At the same time, HHS amended the regulations to streamline the process of adding future emerging infectious diseases. Since the emergence of SARS, CDC has increased legal preparedness for future public health emergencies by establishing a multistate teleconference program for public health lawyers and a Web-based clearinghouse of legal documents.",2004 Feb,"['Misrahi, James J.', 'Foster, Joseph A.', 'Shaw, Frederic E.', 'Cetron, Martin S.']",Emerg Infect Dis,,,True
fbabb5fb318eb82681d448718a79bc44f11a7643,PMC,"SARS among Critical Care Nurses, Toronto",http://dx.doi.org/10.3201/eid1002.030838,PMC3322898,15030692,NO-CC CODE,"To determine factors that predispose or protect healthcare workers from severe acute respiratory syndrome (SARS), we conducted a retrospective cohort study among 43 nurses who worked in two Toronto critical care units with SARS patients. Eight of 32 nurses who entered a SARS patient’s room were infected. The probability of SARS infection was 6% per shift worked. Assisting during intubation, suctioning before intubation, and manipulating the oxygen mask were high-risk activities. Consistently wearing a mask (either surgical or particulate respirator type N95) while caring for a SARS patient was protective for the nurses, and consistent use of the N95 mask was more protective than not wearing a mask. Risk was reduced by consistent use of a surgical mask, but not significantly. Risk was lower with consistent use of a N95 mask than with consistent use of a surgical mask. We conclude that activities related to intubation increase SARS risk and use of a mask (particularly a N95 mask) is protective.",2004 Feb,"['Loeb, Mark', 'McGeer, Allison', 'Henry, Bonnie', 'Ofner, Marianna', 'Rose, David', 'Hlywka, Tammy', 'Levie, Joanne', 'McQueen, Jane', 'Smith, Stephanie', 'Moss, Lorraine', 'Smith, Andrew', 'Green, Karen', 'Walter, Stephen D.']",Emerg Infect Dis,,,True
2c8f94a4a58f03648ff5d88c1d6bff6c6ba7354b,PMC,"SARS-related Virus Predating SARS Outbreak, Hong Kong",http://dx.doi.org/10.3201/eid1002.030533,PMC3322899,15030679,NO-CC CODE,"Using immunofluorescence and neutralization assays, we detected antibodies to human severe acute respiratory syndrome–associated coronavirus (SARS-CoV) and/or animal SARS-CoV–like virus in 17 (1.8%) of 938 adults recruited in 2001. This finding suggests that a small proportion of healthy persons in Hong Kong had been exposed to SARS-related viruses at least 2 years before the recent SARS outbreak.",2004 Feb,"['Zheng, Bo Jian', 'Guan, Yi', 'Wong, Ka Hing', 'Zhou, Jie', 'Wong, Kin Ling', 'Young, Betty Wan Y.', 'Lu, Li Wei', 'Lee, Shui Shan']",Emerg Infect Dis,,,True
55417958dbef828b9c450e7c193bb2cf20cea896,PMC,"Body Temperature Monitoring and SARS Fever Hotline, Taiwan",http://dx.doi.org/10.3201/eid1002.030748,PMC3322900,15030716,NO-CC CODE,"In Taiwan, a temperature-monitoring campaign and hotline for severe acute respiratory syndrome (SARS) fever were implemented in June 2003. Among 1,966 calls, fever was recorded in 19% (n = 378); 18 persons at high risk for SARS were identified. In a cross-sectional telephone survey, 95% (n = 1,060) of households knew about the campaign and 7 households reported fever.",2004 Feb,"['Kaydos-Daniels, S. Cornelia', 'Olowokure, Babatunde', 'Chang, Hong-Jen', 'Barwick, Rachel S.', 'Deng, Jou-Fang', 'Lee, Ming-Liang', 'Kuo, Steve Hsu-Sung', 'Su, Ih-Jen', 'Chen, Kow-Tong', 'Maloney, Susan A.', None]",Emerg Infect Dis,,,False
c85ac6dc2c53a16be7fcdbb1523954da3e053d25,PMC,"Body Temperature Monitoring and SARS Fever Hotline, Taiwan",http://dx.doi.org/10.3201/eid1002.030748,PMC3322900,15030716,NO-CC CODE,"In Taiwan, a temperature-monitoring campaign and hotline for severe acute respiratory syndrome (SARS) fever were implemented in June 2003. Among 1,966 calls, fever was recorded in 19% (n = 378); 18 persons at high risk for SARS were identified. In a cross-sectional telephone survey, 95% (n = 1,060) of households knew about the campaign and 7 households reported fever.",2004 Feb,"['Kaydos-Daniels, S. Cornelia', 'Olowokure, Babatunde', 'Chang, Hong-Jen', 'Barwick, Rachel S.', 'Deng, Jou-Fang', 'Lee, Ming-Liang', 'Kuo, Steve Hsu-Sung', 'Su, Ih-Jen', 'Chen, Kow-Tong', 'Maloney, Susan A.', None]",Emerg Infect Dis,,,True
6e6b122886cf7d009604cdd36ef743ddb632a9c1,PMC,Real-Time Reverse Transcription–Polymerase Chain Reaction Assay for SARS-associated Coronavirus,http://dx.doi.org/10.3201/eid1002.030759,PMC3322901,15030703,NO-CC CODE,"A real-time reverse transcription–polymerase chain reaction (RT-PCR) assay was developed to rapidly detect the severe acute respiratory syndrome–associated coronavirus (SARS-CoV). The assay, based on multiple primer and probe sets located in different regions of the SARS-CoV genome, could discriminate SARS-CoV from other human and animal coronaviruses with a potential detection limit of <10 genomic copies per reaction. The real-time RT-PCR assay was more sensitive than a conventional RT-PCR assay or culture isolation and proved suitable to detect SARS-CoV in clinical specimens. Application of this assay will aid in diagnosing SARS-CoV infection.",2004 Feb,"['Emery, Shannon L.', 'Erdman, Dean D.', 'Bowen, Michael D.', 'Newton, Bruce R.', 'Winchell, Jonas M.', 'Meyer, Richard F.', 'Tong, Suxiang', 'Cook, Byron T.', 'Holloway, Brian P.', 'McCaustland, Karen A.', 'Rota, Paul A.', 'Bankamp, Bettina', 'Lowe, Luis E.', 'Ksiazek, Tom G.', 'Bellini, William J.', 'Anderson, Larry J.']",Emerg Infect Dis,,,True
f11cea7250059fc4acd3955f7d66579d10c11d7e,PMC,Probable Secondary Infections in Households of SARS Patients in Hong Kong,http://dx.doi.org/10.3201/eid1002.030626,PMC3322902,15030689,NO-CC CODE,"Although severe acute respiratory syndrome (SARS) is highly infectious in clinical settings, SARS has not been well examined in household settings. The household and household member attack rates were calculated for 1,214 SARS case-patients and their household members, stratified by two phases of the epidemic. A case-control analysis identified risk factors for secondary infection. Secondary infection occurred in 14.9% (22.1% versus 11% in earlier and later phases) of all households and 8% (11.7% versus 5.9% in the earlier and later phases) of all household members. Healthcare workers’ households were less likely to be affected. Risk factors from the multivariate analysis included at-home duration before hospitalization, hospital visitation to the SARS patient (and mask use during the visit), and frequency of close contact. SARS transmission at the household level was not negligible in Hong Kong. Transmission rates may be greatly reduced with precautionary measures taken by household members of SARS patients.",2004 Feb,"['Lau, Joseph T.F.', 'Lau, Mason', 'Kim, Jean H.', 'Wong, Eric', 'Tsui, Hi-Yi', 'Tsang, Thomas', 'Wong, Tze Wai']",Emerg Infect Dis,,,True
c3cb6dbc8f9856954962672e54253ab8fe627446,PMC,Possible SARS Coronavirus Transmission during Cardiopulmonary Resuscitation,http://dx.doi.org/10.3201/eid1002.030700,PMC3322904,15030699,NO-CC CODE,"Infection of healthcare workers with the severe acute respiratory syndrome–associated coronavirus (SARS-CoV) is thought to occur primarily by either contact or large respiratory droplet transmission. However, infrequent healthcare worker infections occurred despite the use of contact and droplet precautions, particularly during certain aerosol-generating medical procedures. We investigated a possible cluster of SARS-CoV infections in healthcare workers who used contact and droplet precautions during attempted cardiopulmonary resuscitation of a SARS patient. Unlike previously reported instances of transmission during aerosol-generating procedures, the index case-patient was unresponsive, and the intubation procedure was performed quickly and without difficulty. However, before intubation, the patient was ventilated with a bag-valve-mask that may have contributed to aerosolization of SARS-CoV. On the basis of the results of this investigation and previous reports of SARS transmission during aerosol-generating procedures, a systematic approach to the problem is outlined, including the use of the following: 1) administrative controls, 2) environmental engineering controls, 3) personal protective equipment, and 4) quality control.",2004 Feb,"['Christian, Michael D.', 'Loutfy, Mona', 'McDonald, L. Clifford', 'Martinez, Kenneth F.', 'Ofner, Mariana', 'Wong, Tom', 'Wallington, Tamara', 'Gold, Wayne L.', 'Mederski, Barbara', 'Green, Karen', 'Low, Donald E.', None]",Emerg Infect Dis,,,True
321d1c4149caa030f3ad537e3be1ce3a9201571c,PMC,Detection of SARS Coronavirus in Patients with Suspected SARS,http://dx.doi.org/10.3201/eid1002.030610,PMC3322905,15030700,NO-CC CODE,"Cases of severe acute respiratory syndrome (SARS) were investigated for SARS coronavirus (SARS-CoV) through RNA tests, serologic response, and viral culture. Of 537 specimens from patients in whom SARS was clinically diagnosed, 332 (60%) had SARS-CoV RNA in one or more clinical specimens, compared with 1 (0.3%) of 332 samples from controls. Of 417 patients with clinical SARS from whom paired serum samples were available, 92% had an antibody response. Rates of viral RNA positivity increased progressively and peaked at day 11 after onset of illness. Although viral RNA remained detectable in respiratory secretions and stool and urine specimens for >30 days in some patients, virus could not be cultured after week 3 of illness. Nasopharyngeal aspirates, throat swabs, or sputum samples were the most useful clinical specimens in the first 5 days of illness, but later in the illness viral RNA could be detected more readily in stool specimens.",2004 Feb,"['Chan, Kwok H.', 'Poon, Leo L.L.M.', 'Cheng, V.C.C.', 'Guan, Yi', 'Hung, I.F.N.', 'Kong, James', 'Yam, Loretta Y.C.', 'Seto, Wing H.', 'Yuen, Kwok Y.', 'Peiris, Joseph S. Malik']",Emerg Infect Dis,,,True
e065a96a33ccdbcc23e9f7d0af9c5edf440cb478,PMC,Susceptibility of Pigs and Chickens to SARS Coronavirus,http://dx.doi.org/10.3201/eid1002.030677,PMC3322906,15030680,NO-CC CODE,"An outbreak of severe acute respiratory syndrome (SARS) in humans, associated with a new coronavirus, was reported in Southeast Asia, Europe, and North America in early 2003. To address speculations that the virus originated in domesticated animals, or that domestic species were susceptible to the virus, we inoculated 6-week-old pigs and chickens intravenously, intranasally, ocularly, and orally with 10(6) PFU of SARS-associated coronavirus (SARS-CoV). Clinical signs did not develop in any animal, nor were gross pathologic changes evident on postmortem examinations. Attempts at virus isolation were unsuccessful; however, viral RNA was detected by reverse transcriptase-polymerase chain reaction in blood of both species during the first week after inoculation, and in chicken organs at 2 weeks after inoculation. Virus-neutralizing antibodies developed in the pigs. Our results indicate that these animals do not play a role as amplifying hosts for SARS-CoV.",2004 Feb,"['Weingartl, Hana M.', 'Copps, John', 'Drebot, Michael A.', 'Marszal, Peter', 'Smith, Greg', 'Gren, Jason', 'Andonova, Maya', 'Pasick, John', 'Kitching, Paul', 'Czub, Markus']",Emerg Infect Dis,,,True
d624310854291e71dfd4af21d00cc0406d52c7a3,PMC,"Clinical Description of a Completed Outbreak of SARS in Vietnam, February–May, 2003",http://dx.doi.org/10.3201/eid1002.030761,PMC3322907,15030707,NO-CC CODE,"We investigated the clinical manifestations and course of all probable severe acute respiratory syndrome (SARS) patients in the Vietnam outbreak. Probable SARS cases were defined by using the revised World Health Organization criteria. We systematically reviewed medical records and undertook descriptive statistical analyses. All 62 patients were hospitalized. On admission, the most prominent symptoms were malaise (82.3%) and fever (79.0%). Cough, chest pain, and shortness of breath were present in approximately one quarter of the patients; 79.0% had lymphopenia; 40.3% had thrombocytopenia; 19.4% had leukopenia; and 75.8% showed changes on chest radiograph. Fever developed on the first day of illness onset, and both respiratory symptoms and radiographic changes occurred on day 4. On average, maximal radiographic changes were observed on day 10, and fevers subsided by day 13. Symptoms on admission were nonspecific, although fever, malaise, and lymphopenia were common. The complications of SARS included invasive intubation and ventilation (11.3%) and death (9.7%).",2004 Feb,"['Vu, Hoang Thu', 'Leitmeyer, Katrin C.', 'Le, Dang Ha', 'Miller, Megge J.', 'Nguyen, Quang Hien', 'Uyeki, Timothy M.', 'Reynolds, Mary G.', 'Aagesen, Jesper', 'Nicholson, Karl G.', 'Vu, Quang Huy', 'Bach, Huy Anh', 'Plant, Aileen J.']",Emerg Infect Dis,,,True
a8341c6a373e27741446456bce5aae29fa926c52,PMC,SARS Epidemic in the Press,http://dx.doi.org/10.3201/eid1002.030743,PMC3322908,15043015,NO-CC CODE,,2004 Feb,"['Rezza, Giovanni', 'Marino, Raffaella', 'Farchi, Francesca', 'Taranto, Mirella', 'Superiore di Sanità, Istituto', None, None]",Emerg Infect Dis,,,True
44f6a983bc7eba1620e1d53ff2721f9a0aea1a6a,PMC,Combining Clinical and Epidemiologic Features for Early Recognition of SARS,http://dx.doi.org/10.3201/eid1002.030741,PMC3322910,15030706,NO-CC CODE,"Early recognition and rapid initiation of infection control precautions are currently the most important strategies for controlling severe acute respiratory syndrome (SARS). No rapid diagnostic tests currently exist that can rule out SARS among patients with febrile respiratory illnesses. Clinical features alone cannot with certainty distinguish SARS from other respiratory illnesses rapidly enough to inform early management decisions. A balanced approach to screening that allows early recognition of SARS without unnecessary isolation of patients with other respiratory illnesses will require clinicians not only to look for suggestive clinical features but also to routinely seek epidemiologic clues suggestive of SARS coronavirus exposure. Key epidemiologic risk factors include 1) exposure to settings where SARS activity is suspected or documented, or 2) in the absence of such exposure, epidemiologic linkage to other persons with pneumonia (i.e., pneumonia clusters), or 3) exposure to healthcare settings. When combined with clinical findings, these epidemiologic features provide a possible strategic framework for early recognition of SARS.",2004 Feb,"['Jernigan, John A.', 'Low, Donald E.', 'Helfand, Rita F.']",Emerg Infect Dis,,,True
6a45024a424c3a6f8c31fd16d57756a34992b495,PMC,Health Communication during SARS,http://dx.doi.org/10.3201/eid1002.030812,PMC3322911,15030717,NO-CC CODE,"During the severe acute respiratory syndrome (SARS) outbreak, electronic media made it possible to disseminate prevention messages rapidly. The Centers for Disease Control and Prevention’s Travelers’ Health Web site was frequently visited in the first half of 2003; more than 2.6 million visits were made to travel alerts, advisories, and other SARS-related documents.",2004 Feb,"['Arguin, Paul M.', 'Navin, Ava W.', 'Steele, Stefanie F.', 'Weld, Leisa H.', 'Kozarsky, Phyllis E.']",Emerg Infect Dis,,,True
6bccd8e7984b14a10e690519d1d40f5b8a4e4b4c,PMC,"SARS Surveillance during Emergency Public Health Response, United States, March–July 2003",http://dx.doi.org/10.3201/eid1002.030752,PMC3322912,15030681,NO-CC CODE,"In response to the emergence of severe acute respiratory syndrome (SARS), the United States established national surveillance using a sensitive case definition incorporating clinical, epidemiologic, and laboratory criteria. Of 1,460 unexplained respiratory illnesses reported by state and local health departments to the Centers for Disease Control and Prevention from March 17 to July 30, 2003, a total of 398 (27%) met clinical and epidemiologic SARS case criteria. Of these, 72 (18%) were probable cases with radiographic evidence of pneumonia. Eight (2%) were laboratory-confirmed SARS-coronavirus (SARS-CoV) infections, 206 (52%) were SARS-CoV negative, and 184 (46%) had undetermined SARS-CoV status because of missing convalescent-phase serum specimens. Thirty-one percent (124/398) of case-patients were hospitalized; none died. Travel was the most common epidemiologic link (329/398, 83%), and mainland China was the affected area most commonly visited. One case of possible household transmission was reported, and no laboratory-confirmed infections occurred among healthcare workers. Successes and limitations of this emergency surveillance can guide preparations for future outbreaks of SARS or respiratory diseases of unknown etiology.",2004 Feb,"['Schrag, Stephanie J.', 'Brooks, John T.', 'Van Beneden, Chris', 'Parashar, Umesh D.', 'Griffin, Patricia M.', 'Anderson, Larry J.', 'Bellini, William J.', 'Benson, Robert F.', 'Erdman, Dean D.', 'Klimov, Alexander', 'Ksiazek, Thomas G.', 'Peret, Teresa C.T.', 'Talkington, Deborah F.', 'Thacker, W. Lanier', 'Tondella, Maria L.', 'Sampson, Jacquelyn S.', 'Hightower, Allen W.', 'Nordenberg, Dale F.', 'Plikaytis, Brian D.', 'Khan, Ali S.', 'Rosenstein, Nancy E.', 'Treadwell, Tracee A.', 'Whitney, Cynthia G.', 'Fiore, Anthony E.', 'Durant, Tonji M.', 'Perz, Joseph F.', 'Wasley, Annemarie', 'Feikin, Daniel', 'Herndon, Joy L.', 'Bower, William A.', 'Kilbourn, Barbara W.', 'Levy, Deborah A.', 'Coronado, Victor G.', 'Buffington, Joanna', 'Dykewicz, Clare A.', 'Khabbaz, Rima F.', 'Chamberland, Mary E.']",Emerg Infect Dis,,,False
39ee2164fd26eb50a770a31e1fb67c230b4f2ee4,PMC,"SARS Surveillance during Emergency Public Health Response, United States, March–July 2003",http://dx.doi.org/10.3201/eid1002.030752,PMC3322912,15030681,NO-CC CODE,"In response to the emergence of severe acute respiratory syndrome (SARS), the United States established national surveillance using a sensitive case definition incorporating clinical, epidemiologic, and laboratory criteria. Of 1,460 unexplained respiratory illnesses reported by state and local health departments to the Centers for Disease Control and Prevention from March 17 to July 30, 2003, a total of 398 (27%) met clinical and epidemiologic SARS case criteria. Of these, 72 (18%) were probable cases with radiographic evidence of pneumonia. Eight (2%) were laboratory-confirmed SARS-coronavirus (SARS-CoV) infections, 206 (52%) were SARS-CoV negative, and 184 (46%) had undetermined SARS-CoV status because of missing convalescent-phase serum specimens. Thirty-one percent (124/398) of case-patients were hospitalized; none died. Travel was the most common epidemiologic link (329/398, 83%), and mainland China was the affected area most commonly visited. One case of possible household transmission was reported, and no laboratory-confirmed infections occurred among healthcare workers. Successes and limitations of this emergency surveillance can guide preparations for future outbreaks of SARS or respiratory diseases of unknown etiology.",2004 Feb,"['Schrag, Stephanie J.', 'Brooks, John T.', 'Van Beneden, Chris', 'Parashar, Umesh D.', 'Griffin, Patricia M.', 'Anderson, Larry J.', 'Bellini, William J.', 'Benson, Robert F.', 'Erdman, Dean D.', 'Klimov, Alexander', 'Ksiazek, Thomas G.', 'Peret, Teresa C.T.', 'Talkington, Deborah F.', 'Thacker, W. Lanier', 'Tondella, Maria L.', 'Sampson, Jacquelyn S.', 'Hightower, Allen W.', 'Nordenberg, Dale F.', 'Plikaytis, Brian D.', 'Khan, Ali S.', 'Rosenstein, Nancy E.', 'Treadwell, Tracee A.', 'Whitney, Cynthia G.', 'Fiore, Anthony E.', 'Durant, Tonji M.', 'Perz, Joseph F.', 'Wasley, Annemarie', 'Feikin, Daniel', 'Herndon, Joy L.', 'Bower, William A.', 'Kilbourn, Barbara W.', 'Levy, Deborah A.', 'Coronado, Victor G.', 'Buffington, Joanna', 'Dykewicz, Clare A.', 'Khabbaz, Rima F.', 'Chamberland, Mary E.']",Emerg Infect Dis,,,True
66311ae91af1d27827b42b3ad96bca60cb58db03,PMC,"SARS-associated Coronavirus Transmission, United States",http://dx.doi.org/10.3201/eid1002.030734,PMC3322913,15030687,NO-CC CODE,"To better assess the risk for transmission of the severe acute respiratory syndrome–associated coronavirus (SARS-CoV), we obtained serial specimens and clinical and exposure data from seven confirmed U.S. SARS patients and their 10 household contacts. SARS-CoV was detected in a day-14 sputum specimen from one case-patient and in five stool specimens from two case-patients. In one case-patient, SARS-CoV persisted in stool for at least 26 days after symptom onset. The highest amounts of virus were in the day-14 sputum sample and a day-14 stool sample. Residual respiratory symptoms were still present in recovered SARS case-patients 2 months after illness onset. Possible transmission of SARS-CoV occurred in one household contact, but this person had also traveled to a SARS-affected area. The data suggest that SARS-CoV is not always transmitted efficiently. Laboratory diagnosis of SARS-CoV infection is difficult; thus, sputum and stool specimens should be included in the diagnostic work-up for SARS-CoV infection.",2004 Feb,"['Isakbaeva, Elmira T.', 'Khetsuriani, Nino', 'Beard, R. Suzanne', 'Peck, Angela', 'Erdman, Dean', 'Monroe, Stephan S.', 'Tong, Suxiang', 'Ksiazek, Thomas G.', 'Lowther, Sara', 'Smith, Indra Pandya', 'Anderson, Larry J.', 'Lingappa, Jairam', 'Widdowson, Marc-Alain', None]",Emerg Infect Dis,,,True
4b735ca93a77a4443a12ef137288760636db5b41,PMC,Atypical SARS in Geriatric Patient,http://dx.doi.org/10.3201/eid1002.030322,PMC3322914,15030694,NO-CC CODE,"We describe an atypical presentation of severe acute respiratory syndrome (SARS) in a geriatric patient with multiple coexisting conditions. Interpretation of radiographic changes was confounded by cardiac failure, with resolution of fever causing delayed diagnosis and a cluster of cases. SARS should be considered even if a contact history is unavailable, during an ongoing outbreak.",2004 Feb,"['Tee, Augustine K.H.', 'Oh, Helen M.L.', 'Hui, K.P.', 'Lien, Christopher T.C.', 'Narendran, K.', 'Heng, B.H.', 'Ling, A.E.']",Emerg Infect Dis,,,True
f24c7d6af5f673b9dcb3258adf3cba74df3af1d6,PMC,Atypical SARS and Escherichia coli Bacteremia,http://dx.doi.org/10.3201/eid1002.030501,PMC3322915,15030711,NO-CC CODE,We describe a patient with severe acute respiratory syndrome (SARS) whose clinical symptoms were masked by Escherichia coli bacteremia. SARS developed in a cluster of healthcare workers who had contact with this patient. SARS was diagnosed when a chest infiltrate developed and when the patient’s brother was hospitalized with acute respiratory failure. We highlight problems in atypical cases and offer infection control suggestions.,2004 Feb,"['Tan, Thuan Tong', 'Tan, Ban Hock', 'Kurup, Asok', 'Oon, Lynette Lin Ean', 'Heng, Derrick', 'Thoe, Su Yun Se', 'Bai, Xin Lai', 'Chan, Kwai Peng', 'Ling, Ai Ee']",Emerg Infect Dis,,,True
c19a5d9172833a021fd382a55ef79f0fc6ab9119,PMC,SARS Preparedness and Response Planning,http://dx.doi.org/10.3201/eid1002.030803,PMC3322916,15043017,NO-CC CODE,,2004 Feb,"['Parashar, Umesh D.', 'Anderson, Larry J.']",Emerg Infect Dis,,,False
ad2b2d668217156f73fb821ae1228b662724b76a,PMC,SARS-associated Coronavirus Infection in Teenagers,http://dx.doi.org/10.3201/eid1002.030485,PMC3322917,15043016,NO-CC CODE,,2004 Feb,"['Yang, Gee-Gwo', 'Lin, Shinn-Zont', 'Liao, Kuang-Wen', 'Lee, Jen-Jyh', 'Wang, Lih-Shinn']",Emerg Infect Dis,,,True
943f2beb4d32bce84617c72677a277224b73fd8f,PMC,"Lack of SARS Transmission among Public Hospital Workers, Vietnam",http://dx.doi.org/10.3201/eid1002.030707,PMC3322918,15030695,NO-CC CODE,"The severe acute respiratory syndrome (SARS) outbreak in Vietnam was amplified by nosocomial spread within hospital A, but no transmission was reported in hospital B, the second of two designated SARS hospitals. Our study documents lack of SARS-associated coronavirus transmission to hospital B workers, despite variable infection control measures and the use of personal protective equipment.",2004 Feb,"['Ha, Le Dang', 'Bloom, Sharon A.', 'Hien, Nguyen Quang', 'Maloney, Susan A.', 'Mai, Le Quynh', 'Leitmeyer, Katrin C.', 'Anh, Bach Huy', 'Reynolds, Mary G.', 'Montgomery, Joel M.', 'Comer, James A.', 'Horby, PeterW.', 'Plant, Aileen J.']",Emerg Infect Dis,,,True
75f820d5baa32148f309c3661128a6c10a2eee24,PMC,Interferon-β 1a and SARS Coronavirus Replication,http://dx.doi.org/10.3201/eid1002.030482,PMC3322919,15030704,NO-CC CODE,"A global outbreak of severe acute respiratory syndrome (SARS) caused by a novel coronavirus began in March 2003. The rapid emergence of SARS and the substantial illness and death it caused have made it a critical public health issue. Because no effective treatments are available, an intensive effort is under way to identify and test promising antiviral drugs. Here, we report that recombinant human interferon (IFN)-β 1a potently inhibits SARS coronavirus replication in vitro.",2004 Feb,"['Hensley, Lisa E.', 'Fritz, Elizabeth A.', 'Jahrling, Peter B.', 'Karp, Christopher', 'Huggins, John W.', 'Geisbert, Thomas W.']",Emerg Infect Dis,,,True
123d3406f2ad2c3c7f1595a4c4491aaf3a570931,PMC,"Introduction of SARS in France, March–April, 2003",http://dx.doi.org/10.3201/eid1002.030351,PMC3322920,15030682,NO-CC CODE,"We describe severe acute respiratory syndrome (SARS) in France. Patients meeting the World Health Organization definition of a suspected case underwent a clinical, radiologic, and biologic assessment at the closest university-affiliated infectious disease ward. Suspected cases were immediately reported to the Institut de Veille Sanitaire. Probable case-patients were isolated, their contacts quarantined at home, and were followed for 10 days after exposure. Five probable cases occurred from March through April 2003; four were confirmed as SARS coronavirus by reverse transcription–polymerase chain reaction, serologic testing, or both. The index case-patient (patient A), who had worked in the French hospital of Hanoi, Vietnam, was the most probable source of transmission for the three other confirmed cases; two had been exposed to patient A while on the Hanoi-Paris flight of March 22–23. Timely detection, isolation of probable cases, and quarantine of their contacts appear to have been effective in preventing the secondary spread of SARS in France.",2004 Feb,"['Desenclos, Jean-Claude', 'van der Werf, Sylvie', 'Bonmarin, Isabelle', 'Levy-Bruhl, Daniel', 'Yazdanpanah, Yazdan', 'Hoen, Bruno', 'Emmanuelli, Julien', 'Lesens, Olivier', 'Dupon, Michel', 'Natali, François', 'Michelet, Christian', 'Reynes, Jacques', 'Guery, Benoit', 'Larsen, Christine', 'Semaille, Caroline', 'Mouton, Yves', 'Christmann, Daniel', 'André, Michel', 'Escriou, Nicolas', 'Burguière, Anna', 'Manuguerra, Jean-Claude', 'Coignard, Bruno', 'Lepoutre, Agnés', 'Meffre, Christine', 'Bitar, Dounia', 'Decludt, Bénédicte', 'Capek, Isabelle', 'Antona, Denise', 'Che, Didier', 'Herida, Magid', 'Infuso, Andréa', 'Saura, Christine', 'Brücker, Gilles', 'Hubert, Bruno', 'LeGoff, Dominique', 'Scheidegger, Suzanne']",Emerg Infect Dis,,,True
010a3e0b94485b14a46a26d502b3a37fa763b4eb,PMC,"SARS Outbreak, Taiwan, 2003",http://dx.doi.org/10.3201/eid1002.030515,PMC3322921,15030683,NO-CC CODE,"We studied the severe acute respiratory syndrome (SARS) outbreak in Taiwan, using the daily case-reporting data from May 5 to June 4 to learn how it had spread so rapidly. Our results indicate that most SARS-infected persons had symptoms and were admitted before their infections were reclassified as probable cases. This finding could indicate efficient admission, slow reclassification process, or both. The high percentage of nosocomial infections in Taiwan suggests that infection from hospitalized patients with suspected, but not yet classified, cases is a major factor in the spread of disease. Delays in reclassification also contributed to the problem. Because accurate diagnostic testing for SARS is currently lacking, intervention measures aimed at more efficient diagnosis, isolation of suspected SARS patients, and reclassification procedures could greatly reduce the number of infections in future outbreaks.",2004 Feb,"['Hsieh, Ying-Hen', 'Chen, Cathy W.S.', 'Hsu, Sze-Bi']",Emerg Infect Dis,,,False
ddafef49efd9a7dfcdd16c3e6ef2620c78414e34,PMC,"SARS Outbreak, Taiwan, 2003",http://dx.doi.org/10.3201/eid1002.030515,PMC3322921,15030683,NO-CC CODE,"We studied the severe acute respiratory syndrome (SARS) outbreak in Taiwan, using the daily case-reporting data from May 5 to June 4 to learn how it had spread so rapidly. Our results indicate that most SARS-infected persons had symptoms and were admitted before their infections were reclassified as probable cases. This finding could indicate efficient admission, slow reclassification process, or both. The high percentage of nosocomial infections in Taiwan suggests that infection from hospitalized patients with suspected, but not yet classified, cases is a major factor in the spread of disease. Delays in reclassification also contributed to the problem. Because accurate diagnostic testing for SARS is currently lacking, intervention measures aimed at more efficient diagnosis, isolation of suspected SARS patients, and reclassification procedures could greatly reduce the number of infections in future outbreaks.",2004 Feb,"['Hsieh, Ying-Hen', 'Chen, Cathy W.S.', 'Hsu, Sze-Bi']",Emerg Infect Dis,,,False
b45eb2cb079ef2489165f86686645b88c2bac2bb,PMC,"SARS Outbreak, Taiwan, 2003",http://dx.doi.org/10.3201/eid1002.030515,PMC3322921,15030683,NO-CC CODE,"We studied the severe acute respiratory syndrome (SARS) outbreak in Taiwan, using the daily case-reporting data from May 5 to June 4 to learn how it had spread so rapidly. Our results indicate that most SARS-infected persons had symptoms and were admitted before their infections were reclassified as probable cases. This finding could indicate efficient admission, slow reclassification process, or both. The high percentage of nosocomial infections in Taiwan suggests that infection from hospitalized patients with suspected, but not yet classified, cases is a major factor in the spread of disease. Delays in reclassification also contributed to the problem. Because accurate diagnostic testing for SARS is currently lacking, intervention measures aimed at more efficient diagnosis, isolation of suspected SARS patients, and reclassification procedures could greatly reduce the number of infections in future outbreaks.",2004 Feb,"['Hsieh, Ying-Hen', 'Chen, Cathy W.S.', 'Hsu, Sze-Bi']",Emerg Infect Dis,,,True
3f18a67fe497ea56d25018fe7b88b5b5f0925621,PMC,"Serologic and Molecular Biologic Methods for SARS-associated Coronavirus Infection, Taiwan",http://dx.doi.org/10.3201/eid1002.030731,PMC3322922,15030702,NO-CC CODE,"Severe acute respiratory syndrome (SARS) has raised a global alert since March 2003. After its causative agent, SARS-associated coronavirus (SARS-CoV), was confirmed, laboratory methods, including virus isolation, reverse transcriptase–polymerase chain reaction (RT-PCR), and serologic methods, have been quickly developed. In this study, we evaluated four serologic tests ( neutralization test, enzyme-linked immunosorbent assay [ELISA], immunofluorescent assay [IFA], and immunochromatographic test [ICT]) for detecting antibodies to SARS-CoV in sera of 537 probable SARS case-patients with correlation to the RT-PCR . With the neutralization test as a reference method, the sensitivity, specificity, positive predictive value, and negative predictive value were 98.2%, 98.7%, 98.7%, and 98.4% for ELISA; 99.1%, 87.8%, 88.1% and 99.1% for IFA; 33.6%, 98.2%, 95.7%, and 56.1% for ICT, respectively. We also compared the recombinant-based western blot with the whole virus–based IFA and ELISA; the data showed a high correlation between these methods, with an overall agreement of >90%. Our results provide a systematic analysis of serologic and molecular methods for evaluating SARS-CoV infection.",2004 Feb,"['Wu, Ho-Sheng', 'Chiu, Shu-Chun', 'Tseng, Tsan-Chang', 'Lin, Szu-Fong', 'Lin, Jih-Hui', 'Hsu, Yu-Fen', 'Wang, Mei-Ching', 'Lin, Tsuey-Li', 'Yang, Wen-Zieh', 'Ferng, Tian-Lin', 'Huang, Kai-Hung', 'Hsu, Li-Ching', 'Lee, Li-Li', 'Yang, Jyh-Yuan', 'Chen, Hour-Young', 'Su, Shun-Pi', 'Yang, Shih-Yan', 'Lin, Ting-Hsiang', 'Su, Ih-Jen']",Emerg Infect Dis,,,True
24de65541e25ca372d5fb686b733b45a1dd5c0b6,PMC,Multiple Contact Dates and SARS Incubation Periods,http://dx.doi.org/10.3201/eid1002.030426,PMC3322923,15030684,NO-CC CODE,"Many severe acute respiratory syndrome (SARS) patients have multiple possible incubation periods due to multiple contact dates. Multiple contact dates cannot be used in standard statistical analytic techniques, however. I present a simple spreadsheet-based method that uses multiple contact dates to calculate the possible incubation periods of SARS.",2004 Feb,"Meltzer, Martin I.",Emerg Infect Dis,,,True
fdf569ac878048dd7d684ff5c664c5774cd8704b,PMC,Surgical Helmets and SARS Infection,http://dx.doi.org/10.3201/eid1002.030764,PMC3322924,15030697,NO-CC CODE,Performance testing of two brands of surgical helmets indicated that their efficiency at in vivo filtration of sub–micrometer-sized particles is inadequate for their use as respirators. These helmets are not marketed for respiratory protection and should not be used alone for protection against severe acute respiratory syndrome when performing aerosol-generating procedures.,2004 Feb,"['Derrick, James L.', 'Gomersall, Charles D.']",Emerg Infect Dis,,,True
99366c7b20c1a456b14ba2c03cfa67ea0aefcf14,PMC,"Crisis Prevention and Management during SARS Outbreak, Singapore",http://dx.doi.org/10.3201/eid1002.030418,PMC3322925,15030714,NO-CC CODE,"We discuss crisis prevention and management during the first 3 months of the severe acute respiratory syndrome (SARS) outbreak in Singapore. Four public health issues were considered: prevention measures, self-health evaluation, SARS knowledge, and appraisal of crisis management. We conducted telephone interviews with a representative sample of 1,201 adults, ≥21 years of age. We found that sex, age, and attitude (anxiety and perception of open communication with authorities) were associated with practicing preventive measures. Analysis of Singapore’s outbreak improves our understanding of the social dimensions of infectious disease outbreaks.",2004 Feb,"['Quah, Stella R.', 'Hin-Peng, Lee']",Emerg Infect Dis,,,True
5eec2a24d87a846e43dacb1f973271ff481eabc4,PMC,"Crisis Prevention and Management during SARS Outbreak, Singapore",http://dx.doi.org/10.3201/eid1002.030418,PMC3322925,15030714,NO-CC CODE,"We discuss crisis prevention and management during the first 3 months of the severe acute respiratory syndrome (SARS) outbreak in Singapore. Four public health issues were considered: prevention measures, self-health evaluation, SARS knowledge, and appraisal of crisis management. We conducted telephone interviews with a representative sample of 1,201 adults, ≥21 years of age. We found that sex, age, and attitude (anxiety and perception of open communication with authorities) were associated with practicing preventive measures. Analysis of Singapore’s outbreak improves our understanding of the social dimensions of infectious disease outbreaks.",2004 Feb,"['Quah, Stella R.', 'Hin-Peng, Lee']",Emerg Infect Dis,,,True
ea0237728df0d0d6df8c9bf3623c7e696c03a7f3,PMC,Making State Public Health Laws Work for SARS Outbreaks,http://dx.doi.org/10.3201/eid1002.030836,PMC3322926,15043009,NO-CC CODE,,2004 Feb,"['Richards, Edward P.', 'Rathbun, Katharine C.']",Emerg Infect Dis,,,True
4d872182302a82a44112df09c3ca01faa11b93d7,PMC,"Secondary Household Transmission of SARS, Singapore",http://dx.doi.org/10.3201/eid1002.030676,PMC3322927,15030688,NO-CC CODE,Secondary household transmission of severe acute respiratory syndrome (SARS) was studied in 114 households involving 417 contacts. The attack rate was low (6.2%). Occupation of the index case was the factor that most influenced household transmission (adjusted hazard ratio for healthcare workers 0.157; 95% confidence interval 0.042 to 0.588).,2004 Feb,"['Goh, Denise Li-Meng', 'Lee, Bee Wah', 'Chia, Kee Seng', 'Heng, Bee Hoon', 'Chen, Mark', 'Ma, Stefan', 'Tan, Chorh Chuan']",Emerg Infect Dis,,,True
3f0df8f8017cbe949add8bb74b4afb0597e54330,PMC,Possible Central Nervous System Infection by SARS Coronavirus,http://dx.doi.org/10.3201/eid1002.030638,PMC3322928,15030709,NO-CC CODE,"On day 22 of illness, generalized tonic-clonic convulsion developed in a 32-year-old woman with severe acute respiratory syndrome (SARS). Cerebrospinal fluid tested positive for SARS coronavirus (SARS-CoV) by reverse transcriptase–polymerase chain reaction. SARS-CoV may have caused an infection in the central nervous system in this patient.",2004 Feb,"['Lau, Kwok-Kwong', 'Yu, Wai-Cho', 'Chu, Chung-Ming', 'Lau, Suet-Ting', 'Sheng, Bun', 'Yuen, Kwok-Yung']",Emerg Infect Dis,,,True
9305dbadf39b7da72a61b551eb55bda43567b7da,PMC,Index Patient and SARS Outbreak in Hong Kong,http://dx.doi.org/10.3201/eid1002.030645,PMC3322929,15030708,NO-CC CODE,"During the global outbreak of severe acute respiratory syndrome (SARS) in 2003, treatment was empiric. We report the case history of the index patient in a hospital outbreak of SARS in Hong Kong. The patient recovered after conventional antimicrobial therapy. Further studies are needed to address treatment of SARS, which has high attack and death rates.",2004 Feb,"['Wong, Raymond S.M.', 'Hui, David S.']",Emerg Infect Dis,,,True
21a745df80bcdc816a59568b99f3f1fbc87955b3,PMC,"Superspreading SARS Events, Beijing, 2003",http://dx.doi.org/10.3201/eid1002.030732,PMC3322930,15030693,NO-CC CODE,"Superspreading events were pivotal in the global spread of severe acute respiratory syndrome (SARS). We investigated superspreading in one transmission chain early in Beijing’s epidemic. Superspreading was defined as transmission of SARS to at least eight contacts. An index patient with onset of SARS 2 months after hospital admission was the source of four generations of transmission to 76 case-patients, including 12 healthcare workers and several hospital visitors. Four (5%) case circumstances met the superspreading definition. Superspreading appeared to be associated with older age (mean 56 vs. 44 years), case fatality (75% vs. 16%, p = 0.02, Fisher exact test), number of close contacts (36 vs. 0.37) and attack rate among close contacts (43% vs. 18.5%, p < 0.025). Delayed recognition of SARS in a hospitalized patient permitted transmission to patients, visitors, and healthcare workers. Older age and number of contacts merit investigation in future studies of superspreading.",2004 Feb,"['Shen, Zhuang', 'Ning, Fang', 'Zhou, Weigong', 'He, Xiong', 'Lin, Changying', 'Chin, Daniel P.', 'Zhu, Zonghan', 'Schuchat, Anne']",Emerg Infect Dis,,,True
34bb9a7b2786bcb577b96dcc04e0f5e04434935b,PMC,"Risk Factors for SARS among Persons without Known Contact with SARS Patients, Beijing, China",http://dx.doi.org/10.3201/eid1002.030730,PMC3322931,15030685,NO-CC CODE,"Most cases of severe acute respiratory syndrome (SARS) have occurred in close contacts of SARS patients. However, in Beijing, a large proportion of SARS cases occurred in persons without such contact. We conducted a case-control study in Beijing that compared exposures of 94 unlinked, probable SARS patients with those of 281 community-based controls matched for age group and sex. Case-patients were more likely than controls to have chronic medical conditions or to have visited fever clinics (clinics at which possible SARS patients were separated from other patients), eaten outside the home, or taken taxis frequently. The use of masks was strongly protective. Among 31 case-patients for whom convalescent-phase (>21 days) sera were available, 26% had immunoglobulin G to SARS-associated coronavirus. Our finding that clinical SARS was associated with visits to fever clinics supports Beijing’s strategy of closing clinics with poor infection-control measures. Our finding that mask use lowered the risk for disease supports the community’s use of this strategy.",2004 Feb,"['Wu, Jiang', 'Xu, Fujie', 'Zhou, Weigong', 'Feikin, Daniel R.', 'Lin, Chang-Ying', 'He, Xiong', 'Zhu, Zonghan', 'Liang, Wannian', 'Chin, Daniel P.', 'Schuchat, Anne']",Emerg Infect Dis,,,True
d8ba6ed1922432420ce26e3be1fd1f97dbbb5f71,PMC,The Impressive and Rapidly Expanding Knowledge Base on SARS,http://dx.doi.org/10.3201/eid1002.031043,PMC3322932,15040344,NO-CC CODE,,2004 Feb,"Hughes, James M.",Emerg Infect Dis,,,True
25b2102f32004f50167c6d6894d5f4fc6a70b99f,PMC,SARS Transmission among Hospital Workers in Hong Kong,http://dx.doi.org/10.3201/eid1002.030534,PMC3322933,15030698,NO-CC CODE,"Despite infection control measures, breakthrough transmission of severe acute respiratory syndrome (SARS) occurred for many hospital workers in Hong Kong. We conducted a case-control study of 72 hospital workers with SARS and 144 matched controls. Inconsistent use of goggles, gowns, gloves, and caps was associated with a higher risk for SARS infection (unadjusted odds ratio 2.42 to 20.54, p < 0.05). The likelihood of SARS infection was strongly associated with the amount of personal protection equipment perceived to be inadequate, having <2 hours of infection control training, and not understanding infection control procedures. No significant differences existed between the case and control groups in the proportion of workers who performed high-risk procedures, reported minor protection equipment problems, or had social contact with SARS-infected persons. Perceived inadequacy of personal protection equipment supply, infection control training <2 hours, and inconsistent use of personal protection equipment when in contact with SARS patients were significant independent risk factors for SARS infection.",2004 Feb,"['Lau, Joseph T.F.', 'Fung, Kitty S.', 'Wong, Tze Wai', 'Kim, Jean H.', 'Wong, Eric', 'Chung, Sydney', 'Ho, Deborah', 'Chan, Louis Y.', 'Lui, S.F.', 'Cheng, Augustine']",Emerg Infect Dis,,,True
69ad5dfa7eb8ada52f203b2130a89ecf2ec5c6fa,PMC,Ultrastructural Characterization of SARS Coronavirus,http://dx.doi.org/10.3201/eid1002.030913,PMC3322934,15030705,NO-CC CODE,"Severe acute respiratory syndrome (SARS) was first described during a 2002–2003 global outbreak of severe pneumonia associated with human deaths and person-to-person disease transmission. The etiologic agent was initially identified as a coronavirus by thin-section electron microscopic examination of a virus isolate. Virions were spherical, 78 nm in mean diameter, and composed of a helical nucleocapsid within an envelope with surface projections. Herein, we show that infection with the SARS-associated coronavirus resulted in distinct ultrastructural features: double-membrane vesicles, nucleocapsid inclusions, and large granular areas of cytoplasm. These three structures and the coronavirus particles were shown to be positive for viral proteins and RNA by using ultrastructural immunogold and in situ hybridization assays. In addition, ultrastructural examination of a bronchiolar lavage specimen from a SARS patient showed numerous coronavirus-infected cells with features similar to those in infected culture cells. Electron microscopic studies were critical in identifying the etiologic agent of the SARS outbreak and in guiding subsequent laboratory and epidemiologic investigations.",2004 Feb,"['Goldsmith, Cynthia S.', 'Tatti, Kathleen M.', 'Ksiazek, Thomas G.', 'Rollin, Pierre E.', 'Comer, James A.', 'Lee, William W.', 'Rota, Paul A.', 'Bankamp, Bettina', 'Bellini, William J.', 'Zaki, Sherif R.']",Emerg Infect Dis,,,True
5ad3a3198af0dc26625b9ad9196cb2f1a65aa248,PMC,"Real-Time Polymerase Chain Reaction for Detecting SARS Coronavirus, Beijing, 2003",http://dx.doi.org/10.3201/eid1002.030799,PMC3322935,15030701,NO-CC CODE,"During the 2003 severe acute respiratory syndrome (SARS) outbreak, a real-time quantitative polymerase chain reaction, which targets the nucleocapsid gene at the 3′-end of the viral genome, was established to detect and identify the SARS-associated coronavirus. We describe the use of this assay to screen >700 clinical samples.",2004 Feb,"['Zhai, Junhui', 'Briese, Thomas', 'Dai, Erhei', 'Wang, Xiaoyi', 'Pang, Xin', 'Du, Zongmin', 'Liu, Haihong', 'Wang, Jin', 'Wang, Hongxia', 'Guo, Zhaobiao', 'Chen, Zeliang', 'Jiang, Lingxiao', 'Zhou, Dongsheng', 'Han, Yanping', 'Jabado, Omar', 'Palacios, Gustavo', 'Lipkin, W. Ian', 'Yang, Ruifu']",Emerg Infect Dis,,,True
d283e04661726366d5eb583ddbb927d630d89852,PMC,Healthcare Worker Seroconversion in SARS Outbreak,http://dx.doi.org/10.3201/eid1002.030397,PMC3322936,15030691,NO-CC CODE,"Serum samples were obtained from healthcare workers 5 weeks after exposure to an outbreak of severe acute respiratory syndrome (SARS). A sensitive dot blot enzyme-linked immunosorbent assay, complemented by a specific neutralization test, shows that only persons in whom probable SARS was diagnosed had specific antibodies and suggests that subclinical SARS is not an important feature of the disease.",2004 Feb,"['Chow, Pierce K. H.', 'Ooi, Eng-Eong', 'Tan, Hiang-Khoon', 'Ong, Kong-Wee', 'Sil, Bijon Kumar', 'Teo, Melissa', 'Ng, Timothy', 'Soo, Khee-Chee']",Emerg Infect Dis,,,True
d2f5ff7d542090b94032fa81f1e22ec4c3c4ffef,PMC,"Lack of SARS Transmission among Healthcare Workers, United States",http://dx.doi.org/10.3201/eid1002.030793,PMC3322937,15030686,NO-CC CODE,"Healthcare workers accounted for a large proportion of persons with severe acute respiratory syndrome (SARS) during the worldwide epidemic of early 2003. We conducted an investigation of healthcare workers exposed to laboratory-confirmed SARS patients in the United States to evaluate infection-control practices and possible SARS-associated coronavirus (SARS-CoV) transmission. We identified 110 healthcare workers with exposure within droplet range (i.e., 3 feet) to six SARS-CoV–positive patients. Forty-five healthcare workers had exposure without any mask use, 72 had exposure without eye protection, and 40 reported direct skin-to-skin contact. Potential droplet- and aerosol-generating procedures were infrequent: 5% of healthcare workers manipulated a patient’s airway, and 4% administered aerosolized medication. Despite numerous unprotected exposures, there was no serologic evidence of healthcare-related SARS-CoV transmission. Lack of transmission in the United States may be related to the relative absence of high-risk procedures or patients, factors that may place healthcare workers at higher risk for infection.",2004 Feb,"['Park, Benjamin J.', 'Peck, Angela J.', 'Kuehnert, Matthew J.', 'Newbern, Claire', 'Smelser, Chad', 'Comer, James A.', 'Jernigan, Daniel', 'McDonald, L. Clifford']",Emerg Infect Dis,,,True
25ad613a571cd6c9f3ea5af6727a7b1af41eb763,PMC,"Global Surveillance, National Surveillance, and SARS",http://dx.doi.org/10.3201/eid1002.031038,PMC3322938,15040346,NO-CC CODE,,2004 Feb,"['Heymann, David L.', 'Rodier, Guénaël']",Emerg Infect Dis,,,True
1af6f8be4db8c2fb39dccbc04ea21d8e263af56a,PMC,"Cluster of SARS among Medical Students Exposed to Single Patient, Hong Kong",http://dx.doi.org/10.3201/eid1002.030452,PMC3322939,15030696,NO-CC CODE,"We studied transmission patterns of severe acute respiratory syndrome (SARS) among medical students exposed exclusively to the first SARS patient in the Prince of Wales Hospital in Hong Kong, before his illness was recognized. We conducted a retrospective cohort study of 66 medical students who visited the index patient’s ward, including 16 students with SARS and 50 healthy students. The risk of contracting SARS was sevenfold greater among students who definitely visited the index case’s cubicle than in those who did not (10/27 [41%] versus 1/20 [5%], relative risk [RR] 7.4; 95% confidence interval [CI] 1.0 to 53.3). Illness rates increased directly with proximity of exposure to the index case. However, four of eight students who were in the same cubicle, but were not within 1 m of the index case-patient, contracted SARS. Proximity to the index case-patient was associated with transmission, which is consistent with droplet spread. Transmission through fomites or small aerosols cannot be ruled out.",2004 Feb,"['Wong, Tze-wai', 'Lee, Chin-kei', 'Tam, Wilson', 'Lau, Joseph Tak-fai', 'Yu, Tak-sun', 'Lui, Siu-fai', 'Chan, Paul K.S.', 'Li, Yuguo', 'Bresee, Joseph S.', 'Sung, Joseph J.Y.', 'Parashar, Umesh D.', None]",Emerg Infect Dis,,,True
19771e5bae9637f1f2d1c788e9089d17ebf37c42,PMC,Fear and Stigma: The Epidemic within the SARS Outbreak,http://dx.doi.org/10.3201/eid1002.030750,PMC3322940,15030713,NO-CC CODE,"Because of their evolving nature and inherent scientific uncertainties, outbreaks of emerging infectious diseases can be associated with considerable fear in the general public or in specific communities, especially when illness and deaths are substantial. Mitigating fear and discrimination directed toward persons infected with, and affected by, infectious disease can be important in controlling transmission. Persons who are feared and stigmatized may delay seeking care and remain in the community undetected. This article outlines efforts to rapidly assess, monitor, and address fears associated with the 2003 severe acute respiratory syndrome (SARS) epidemic in the United States. Although fear, stigmatization, and discrimination were not widespread in the general public, Asian-American communities were particularly affected.",2004 Feb,"['Person, Bobbie', 'Sy, Francisco', 'Holton, Kelly', 'Govert, Barbara', 'Liang, Arthur', None, None, 'Garza, Brenda', 'Gould, Deborah', 'Hickson, Meredith', 'McDonald, Marian', 'Meijer, Cecilia', 'Smith, Julia', 'Veto, Liza', 'Williams, Walter', 'Zauderer, Laura']",Emerg Infect Dis,,,True
1b025e30cb06c0149473a80f39ae2194bc5f0b27,PMC,"Vets, Meds, and Zoonotic Threats",http://dx.doi.org/10.3201/eid1004.030805,PMC3323071,15212004,NO-CC CODE,"The fourth international conference on emerging zoonoses (September 18–21, Ames, Iowa, USA) brought together 180 scientists and healthcare specialists from 18 countries working to control diseases transmitted from animals to humans. The meeting took place under the auspices of the Center of Food Security and Public Health, USA, and the Institute for International Cooperation in Animal Biologics (a collaborating center of the World Animal Health Organisation [OIE]).",2004 Apr,"Pitlik, Silvio",Emerg Infect Dis,,,False
8e152f8144e2d2ea5b829aa4b7089a49fa903453,PMC,Inhibition of SARS Coronavirus Infection In Vitro with Clinically Approved Antiviral Drugs,http://dx.doi.org/10.3201/eid1004.030458,PMC3323075,15200845,NO-CC CODE,"Severe acute respiratory syndrome (SARS) is an infectious disease caused by a newly identified human coronavirus (SARS-CoV). Currently, no effective drug exists to treat SARS-CoV infection. In this study, we investigated whether a panel of commercially available antiviral drugs exhibit in vitro anti–SARS-CoV activity. A drug-screening assay that scores for virus-induced cytopathic effects on cultured cells was used. Tested were 19 clinically approved compounds from several major antiviral pharmacologic classes: nucleoside analogs, interferons, protease inhibitors, reverse transcriptase inhibitors, and neuraminidase inhibitors. Complete inhibition of cytopathic effects of SARS-CoV in culture was observed for interferon subtypes, β-1b, α-n1, α-n3, and human leukocyte interferon α. These findings support clinical testing of approved interferons for the treatment of SARS.",2004 Apr,"['Tan, Emily L.C.', 'Ooi, Eng Eong', 'Lin, Chin-Yo', 'Tan, Hwee Cheng', 'Ling, Ai Ee', 'Lim, Bing', 'Stanton, Lawrence W.']",Emerg Infect Dis,,,True
8551fc3e19170f1f99d325d6a3283d9a91493d61,PMC,"SARS Transmission, Risk Factors, and Prevention in Hong Kong",http://dx.doi.org/10.3201/eid1004.030628,PMC3323085,15200846,NO-CC CODE,"We analyzed information obtained from 1,192 patients with probable severe acute respiratory syndrome (SARS) reported in Hong Kong. Among them, 26.6% were hospital workers, 16.1% were household members of SARS patients and had probable secondary infections, 14.3% were Amoy Garden residents, 4.9% were inpatients, and 20.1% were contacts of SARS patients who were not family members. The remaining 347 case-patients (29.1%) did not have “known” sources of infection. Excluding those <16 years of age, 330 patients with cases from “undefined” sources were used in a 1:2 matched case-control study. Multivariate analysis of this case-control study showed that having visited mainland China, hospitals, or the Amoy Gardens were risk factors (odds ratio [OR] 1.95 to 7.63). In addition, frequent mask use in public venues, frequent hand washing, and disinfecting the living quarters were significant protective factors (OR 0.36 to 0.58). In Hong Kong, therefore, community-acquired infection did not make up most transmissions, and public health measures have contributed substantially to the control of the SARS epidemic.",2004 Apr,"['Lau, Joseph T.F.', 'Tsui, Hiyi', 'Lau, Mason', 'Yang, Xilin']",Emerg Infect Dis,,,True
2144267cf424681c6f75208bd17198b59e630fe2,PMC,Human Challenge Pilot Study with Cyclospora cayetanensis,http://dx.doi.org/10.3201/eid1004.030356,PMC3323087,15200870,NO-CC CODE,"We describe a pilot study that attempted to infect human volunteers with Cyclospora cayetanensis. Seven healthy volunteers ingested an inoculum of Cyclospora oocysts (approximately 200–49,000 oocysts). The volunteers did not experience symptoms of gastroenteritis, and no oocysts were detected in any stool samples during the 16 weeks volunteers were monitored.",2004 Apr,"['Alfano-Sobsey, Edith M.', 'Eberhard, Mark L.', 'Seed, John R.', 'Weber, David J.', 'Won, Kimberly Y.', 'Nace, Eva K.', 'Moe, Christine L.']",Emerg Infect Dis,,,True
2ded225df8c6a428c0356f30df7656d574b648e6,PMC,Epidemiologic Clues to SARS Origin in China,http://dx.doi.org/10.3201/eid1006.030852,PMC3323155,15207054,NO-CC CODE,"An epidemic of severe acute respiratory syndrome (SARS) began in Foshan municipality, Guangdong Province, China, in November 2002. We studied SARS case reports through April 30, 2003, including data from case investigations and a case series analysis of index cases. A total of 1,454 clinically confirmed cases (and 55 deaths) occurred; the epidemic peak was in the first week of February 2003. Healthcare workers accounted for 24% of cases. Clinical signs and symptoms differed between children (<18 years) and older persons (>65 years). Several observations support the hypothesis of a wild animal origin for SARS. Cases apparently occurred independently in at least five different municipalities; early case-patients were more likely than later patients to report living near a produce market (odds ratio undefined; lower 95% confidence interval 2.39) but not near a farm; and 9 (39%) of 23 early patients, including 6 who lived or worked in Foshan, were food handlers with probable animal contact.",2004 Jun,"['Xu, Rui-Heng', 'He, Jian-Feng', 'Evans, Meirion R.', 'Peng, Guo-Wen', 'Field, Hume E', 'Yu, De-Wen', 'Lee, Chin-Kei', 'Luo, Hui-Min', 'Lin, Wei-Sheng', 'Lin, Peng', 'Li, Ling-Hui', 'Liang, Wen-Jia', 'Lin, Jin-Yan', 'Schnur, Alan']",Emerg Infect Dis,,,True
03e352c35635f746ff112e5a766eefe10efb59b4,PMC,SARS Epidemiology Modeling,http://dx.doi.org/10.3201/eid1006.031023,PMC3323156,15224675,NO-CC CODE,,2004 Jun,"['Hsieh, Ying-Hen', 'Lee, Jen-Yu', 'Chang, Hsiao-Ling']",Emerg Infect Dis,,,True
c842b8c5487911096f23f2894b690620e511c522,PMC,SARS Exposure and Emergency Department Workers,http://dx.doi.org/10.3201/eid1006.030972,PMC3323160,15207066,NO-CC CODE,"Of 193 emergency department workers exposed to severe acute respiratory syndrome (SARS), 9 (4.7%) were infected. Pneumonia developed in six workers, and assays showed anti-SARS immunoglobulin (Ig) M and IgG. The other three workers were IgM-positive and had lower IgG titers; in two, mild illness developed, and one remained asymptomatic.",2004 Jun,"['Chang, Wei-Tien', 'Kao, Chuan-Liang', 'Chung, Ming-Yi', 'Chen, Shyr-Chyr', 'Lin, Shou-Ju', 'Chiang, Wen-Chu', 'Chen, Shey-Ying', 'Su, Chan-Ping', 'Hsueh, Po-Ren', 'Chen, Wen-Jone', 'Chen, Pei-Jer', 'Yang, Pan-Chyr']",Emerg Infect Dis,,,True
6a53c9947edc4772e593300a652b20875114befe,PMC,Diagnostic Criteria during SARS Outbreak in Hong Kong,http://dx.doi.org/10.3201/eid1006.030618,PMC3323171,15224676,NO-CC CODE,,2004 Jun,"['Chan, Louis Y.', 'Lee, Nelson', 'Chan, Paul K.S.', 'Wu, Alan', 'Rainer, Timothy H.', 'Li, Philip K.T.', 'Fung, Hong', 'Sung, Joseph JY']",Emerg Infect Dis,,,True
db5f07cca2e8c9d47193fa957565147e7fad8d10,PMC,SARS and Common Viral Infections,http://dx.doi.org/10.3201/eid1006.030863,PMC3323182,15207072,NO-CC CODE,"In California, molecular testing was useful in decreasing suspicion for severe acute respiratory syndrome (SARS), by detecting common respiratory pathogens (influenza A/B, human metapneumovirus, picornavirus, Mycoplasma pneumoniae, Chlamydia spp., parainfluenza virus, respiratory syncytial virus, and adenovirus) in 23 (45%) of 51 patients with suspected SARS and 9 (47%) of 19 patients with probable SARS.",2004 Jun,"['Louie, Janice K.', 'Hacker, Jill K.', 'Mark, Jennifer', 'Gavali, Shilpa S.', 'Yagi, Shigeo', 'Espinosa, Alex', 'Schnurr, David P.', 'Cossen, Cynthia K.', 'Isaacson, Erin R.', 'Glaser, Carol A.', 'Fischer, Marc', 'Reingold, Arthur L.', 'Vugia, Duc J.', None, None]",Emerg Infect Dis,,,True
d4147c3df65fb378821ec21f5171668cdd76ceae,PMC,Respiratory Picornaviruses and Respiratory Syncytial Virus as Causative Agents of Acute Expiratory Wheezing in Children,http://dx.doi.org/10.3201/eid1006.030629,PMC3323183,15207063,NO-CC CODE,"We studied the viral etiology of acute expiratory wheezing (bronchiolitis, acute asthma) in 293 hospitalized children in a 2-year prospective study in Finland. A potential causative viral agent was detected in 88% of the cases. Eleven different viruses were represented. Respiratory syncytial virus (RSV) (27%), enteroviruses (25%), rhinovirus (24%), and nontypable rhino/enterovirus (16%) were found most frequently. In infants, RSV was found in 54% and respiratory picornaviruses (rhinovirus and enteroviruses) in 42% of the cases. In older children, respiratory picornaviruses dominated (65% of children ages 1-2 years and 82% of children ages >3 years). Human metapneumovirus was detected in 4% of all children and in 11% of infants. To prevent and treat acute expiratory wheezing illnesses in children, efforts should be focused on RSV, enterovirus, and rhinovirus infections.",2004 Jun,"['Jartti, Tuomas', 'Lehtinen, Pasi', 'Vuorinen, Tytti', 'Österback, Riikka', 'van den Hoogen, Bernadette', 'Osterhaus, Albert D.M.E.', 'Ruuskanen, Olli']",Emerg Infect Dis,,,True
e7e37189d093df46af346624bfbd0386fd0796f8,PMC,Ring Vaccination and Smallpox Control,http://dx.doi.org/10.3201/eid1005.030419,PMC3323203,15200816,NO-CC CODE,"We present a stochastic model for the spread of smallpox after a small number of index cases are introduced into a susceptible population. The model describes a branching process for the spread of the infection and the effects of intervention measures. We discuss scenarios in which ring vaccination of direct contacts of infected persons is sufficient to contain an epidemic. Ring vaccination can be successful if infectious cases are rapidly diagnosed. However, because of the inherent stochastic nature of epidemic outbreaks, both the size and duration of contained outbreaks are highly variable. Intervention requirements depend on the basic reproduction number R(0), for which different estimates exist. When faced with the decision of whether to rely on ring vaccination, the public health community should be aware that an epidemic might take time to subside even for an eventually successful intervention strategy.",2004 May,"['Kretzschmar, Mirjam', 'van den Hof, Susan', 'Wallinga, Jacco', 'van Wijngaarden, Jan']",Emerg Infect Dis,,,False
68680c43a6baf085d18dbc567d93647d2d01ce72,PMC,Ring Vaccination and Smallpox Control,http://dx.doi.org/10.3201/eid1005.030419,PMC3323203,15200816,NO-CC CODE,"We present a stochastic model for the spread of smallpox after a small number of index cases are introduced into a susceptible population. The model describes a branching process for the spread of the infection and the effects of intervention measures. We discuss scenarios in which ring vaccination of direct contacts of infected persons is sufficient to contain an epidemic. Ring vaccination can be successful if infectious cases are rapidly diagnosed. However, because of the inherent stochastic nature of epidemic outbreaks, both the size and duration of contained outbreaks are highly variable. Intervention requirements depend on the basic reproduction number R(0), for which different estimates exist. When faced with the decision of whether to rely on ring vaccination, the public health community should be aware that an epidemic might take time to subside even for an eventually successful intervention strategy.",2004 May,"['Kretzschmar, Mirjam', 'van den Hof, Susan', 'Wallinga, Jacco', 'van Wijngaarden, Jan']",Emerg Infect Dis,,,True
caf34dc95f513eba16331c99fbe0a1cbf1fe2557,PMC,"Clinical Manifestations, Laboratory Findings, and Treatment Outcomes of SARS Patients",http://dx.doi.org/10.3201/eid1005.030640,PMC3323212,15200814,NO-CC CODE,"Clinical and laboratory data on severe acute respiratory syndrome (SARS), particularly on the temporal progression of abnormal laboratory findings, are limited. We conducted a prospective study on the clinical, radiologic, and hematologic findings of SARS patients with pneumonia, who were admitted to National Taiwan University Hospital from March 8 to June 15, 2003. Fever was the most frequent initial symptom, followed by cough, myalgia, dyspnea, and diarrhea. Twenty-four patients had various underlying diseases. Most patients had elevated C-reactive protein (CRP) levels and lymphopenia. Other common abnormal laboratory findings included leukopenia, thrombocytopenia, and elevated levels of aminotransferase, lactate dehydrogenase, and creatine kinase. These clinical and laboratory findings were exacerbated in most patients during the second week of disease. The overall case-fatality rate was 19.7%. By multivariate analysis, underlying disease and initial CRP level were predictive of death.",2004 May,"['Wang, Jann-Tay', 'Sheng, Wang-Huei', 'Fang, Chi-Tai', 'Chen, Yee-Chun', 'Wang, Jiun-Ling', 'Yu, Chong-Jen', 'Chang, Shan-Chwen', 'Yang, Pan-Chyr']",Emerg Infect Dis,,,True
b7f1dcfe8b12d6b8a548db0de597cbef95712d9c,PMC,Laboratory Diagnosis of SARS,http://dx.doi.org/10.3201/eid1005.030682,PMC3323215,15200815,NO-CC CODE,"The virologic test results of 415 patients with severe acute respiratory syndrome (SARS) were examined. The peak detection rate for SARS-associated coronavirus occurred at week 2 after illness onset for respiratory specimens, at weeks 2 to 3 for stool or rectal swab specimens, and at week 4 for urine specimens. The latest stool sample that was positive by reverse transcription–polymerase chain reaction (RT-PCR) was collected on day 75 while the patient was receiving intensive care. Tracheal aspirate and stool samples had a higher diagnostic yield (RT-PCR average positive rate for first 2 weeks: 66.7% and 56.5%, respectively). Pooled throat and nasal swabs, rectal swab, nasal swab, throat swab, and nasopharyngeal aspirate specimens provided a moderate yield (29.7%–40.0%), whereas throat washing and urine specimens showed a lower yield (17.3% and 4.5%). The collection procedures for stool and pooled nasal and throat swab specimens were the least likely to transmit infection, and the combination gave the highest yield for coronavirus detection by RT-PCR. Positive virologic test results in patient groups were associated with mechanical ventilation or death (p < 0.001), suggesting a correlation between viral load and disease severity.",2004 May,"['Chan, Paul K. S.', 'To, Wing-Kin', 'Ng, King-Cheung', 'Lam, Rebecca K. Y.', 'Ng, Tak-Keung', 'Chan, Rickjason C. W.', 'Wu, Alan', 'Yu, Wai-Cho', 'Lee, Nelson', 'Hui, David S. C.', 'Lai, Sik-To', 'Hon, Ellis K. L.', 'Li, Chi-Kong', 'Sung, Joseph J. Y.', 'Tam, John S.']",Emerg Infect Dis,,,True
44b17c2f802ed2716fdf040dc05633b35d4b6dcb,PMC,Animal-to-Human SARS-associated Coronavirus Transmission?,http://dx.doi.org/10.3201/eid1005.040022,PMC3323218,15216845,NO-CC CODE,,2004 May,"['Lun, Zhao-Rong', 'Qu, Liang-Hu']",Emerg Infect Dis,,,True
66435f60ea3030e572cc8306d4e7be3354737583,PMC,SARS in Hospital Emergency Room,http://dx.doi.org/10.3201/eid1005.030579,PMC3323223,15200809,NO-CC CODE,"Thirty-one cases of severe acute respiratory syndrome (SARS) occurred after exposure in the emergency room at the National Taiwan University Hospital. The index patient was linked to an outbreak at a nearby municipal hospital. Three clusters were identified over a 3-week period. The first cluster (5 patients) and the second cluster (14 patients) occurred among patients, family members, and nursing aids. The third cluster (12 patients) occurred exclusively among healthcare workers. Six healthcare workers had close contact with SARS patients. Six others, with different working patterns, indicated that they did not have contact with a SARS patient. Environmental surveys found 9 of 119 samples of inanimate objects to be positive for SARS coronavirus RNA. These observations indicate that although transmission by direct contact with known SARS patients was responsible for most cases, environmental contamination with the SARS coronavirus may have lead to infection among healthcare workers without documented contact with known hospitalized SARS patients.",2004 May,"['Chen, Yee-Chun', 'Huang, Li-Min', 'Chan, Chang-Chuan', 'Su, Chan-Ping', 'Chang, Shan-Chwen', 'Chang, Ying-Ying', 'Chen, Mei-Ling', 'Hung, Chien-Ching', 'Chen, Wen-Jone', 'Lin, Fang-Yue', 'Lee, Yuan-Teh', None]",Emerg Infect Dis,,,True
d7c1bff961955e099a23dd51fd2a7734069bd942,PMC,Genetic Variation of SARS Coronavirus in Beijing Hospital,http://dx.doi.org/10.3201/eid1005.030875,PMC3323231,15200810,NO-CC CODE,"To characterize genetic variation of severe acute respiratory syndrome–associated coronavirus (SARS-CoV) transmitted in the Beijing area during the epidemic outbreak of 2003, we sequenced 29 full-length S genes of SARS-CoV from 20 hospitalized SARS patients on our unit, the Beijing 302 Hospital. Viral RNA templates for the S-gene amplification were directly extracted from raw clinical samples, including plasma, throat swab, sputum, and stool, during the course of the epidemic in the Beijing area. We used a TA-cloning assay with direct analysis of nested reverse transcription–polymerase chain reaction products in sequence. One hundred thirteen sequence variations with nine recurrent variant sites were identified in analyzed S-gene sequences compared with the BJ01 strain of SARS-CoV. Among them, eight variant sites were, we think, the first documented. Our findings demonstrate the coexistence of S-gene sequences with and without substitutions (referred to BJ01) in samples analyzed from some patients.",2004 May,"['Xu, Dongping', 'Zhang, Zheng', 'Chu, Fuliang', 'Li, Yonggang', 'Jin, Lei', 'Zhang, Lingxia', 'Gao, George F.', 'Wang, Fu-Sheng']",Emerg Infect Dis,,,True
d911768dd0b8ffceaa878966a9196a26eda89e42,PMC,"Domestic Poultry and SARS Coronavirus, Southern China",http://dx.doi.org/10.3201/eid1005.030827,PMC3323233,15200830,NO-CC CODE,"SARS coronavirus injected intratracheally into chickens, turkeys, geese, ducks, and quail, or into the allantoic sac of their embryonating eggs, failed to cause disease or replicate. This finding suggests that domestic poultry were unlikely to have been the reservoir, or associated with dissemination, of SARS coronavirus in the animal markets of southern China.",2004 May,"['Swayne, David E.', 'Suarez, David L.', 'Spackman, Erica', 'Tumpey, Terrence M.', 'Beck, Joan R.', 'Erdman, Dean', 'Rollin, Pierre E.', 'Ksiazek, Thomas G.']",Emerg Infect Dis,,,True
b29b3863f312e1de39f2246ca14e563a5b7642c3,PMC,Hospital Preparedness and SARS,http://dx.doi.org/10.3201/eid1005.030717,PMC3323236,15200807,NO-CC CODE,"On May 23, 2003, Toronto experienced the second phase of a severe acute respiratory syndrome (SARS) outbreak. Ninety cases were confirmed, and >620 potential cases were managed. More than 9,000 persons had contact with confirmed or potential case-patients; many required quarantine. The main hospital involved during the second outbreak was North York General Hospital. We review this hospital’s response to, and management of, this outbreak, including such factors as building preparation and engineering, personnel, departmental workload, policies and documentation, infection control, personal protective equipment, training and education, public health, management and administration, follow-up of SARS patients, and psychological and psychosocial management and research. We also make recommendations for other institutions to prepare for future outbreaks, regardless of their origin.",2004 May,"['Loutfy, Mona R.', 'Wallington, Tamara', 'Rutledge, Tim', 'Mederski, Barbara', 'Rose, Keith', 'Kwolek, Sue', 'McRitchie, Donna', 'Ali, Azra', 'Wolff, Bryan', 'White, Diane', 'Glassman, Edward', 'Ofner, Marianna', 'Low, Don E.', 'Berger, Lisa', 'McGeer, Allison', 'Wong, Tom', 'Baron, David', 'Berall, Glenn']",Emerg Infect Dis,,,False
4667d92ff3cfe1a4ac0c714cf7152e7c7c430a0e,PMC,Hospital Preparedness and SARS,http://dx.doi.org/10.3201/eid1005.030717,PMC3323236,15200807,NO-CC CODE,"On May 23, 2003, Toronto experienced the second phase of a severe acute respiratory syndrome (SARS) outbreak. Ninety cases were confirmed, and >620 potential cases were managed. More than 9,000 persons had contact with confirmed or potential case-patients; many required quarantine. The main hospital involved during the second outbreak was North York General Hospital. We review this hospital’s response to, and management of, this outbreak, including such factors as building preparation and engineering, personnel, departmental workload, policies and documentation, infection control, personal protective equipment, training and education, public health, management and administration, follow-up of SARS patients, and psychological and psychosocial management and research. We also make recommendations for other institutions to prepare for future outbreaks, regardless of their origin.",2004 May,"['Loutfy, Mona R.', 'Wallington, Tamara', 'Rutledge, Tim', 'Mederski, Barbara', 'Rose, Keith', 'Kwolek, Sue', 'McRitchie, Donna', 'Ali, Azra', 'Wolff, Bryan', 'White, Diane', 'Glassman, Edward', 'Ofner, Marianna', 'Low, Don E.', 'Berger, Lisa', 'McGeer, Allison', 'Wong, Tom', 'Baron, David', 'Berall, Glenn']",Emerg Infect Dis,,,True
634ff899aa23d42b3a4941bdf96ad6063edcc206,PMC,"Infection Control and SARS Transmission among Healthcare Workers, Taiwan",http://dx.doi.org/10.3201/eid1005.030777,PMC3323237,15200825,NO-CC CODE,"This study found infrequent transmission of severe acute respiratory syndrome (SARS) coronavirus to healthcare workers involved in the care of the first five case-patients in Taiwan, despite a substantial number of unprotected exposures. Nonetheless, given that SARS has been highly transmissible on some occasions, we still recommend strict precautions.",2004 May,"['Chen, Yee-Chun', 'Chen, Pei-Jer', 'Chang, Shan-Chwen', 'Kao, Chiang-Lian', 'Wang, Shiou-Hwa', 'Wang, Li-Hua', 'Yang, Pan-Chyr', None]",Emerg Infect Dis,,,True
d6f24e997f0b166dba199b275aaeb5d1f4f6c44c,PMC,"SARS in Healthcare Facilities, Toronto and Taiwan",http://dx.doi.org/10.3201/eid1005.030791,PMC3323242,15200808,NO-CC CODE,"The healthcare setting was important in the early spread of severe acute respiratory syndrome (SARS) in both Toronto and Taiwan. Healthcare workers, patients, and visitors were at increased risk for infection. Nonetheless, the ability of individual SARS patients to transmit disease was quite variable. Unrecognized SARS case-patients were a primary source of transmission and early detection and intervention were important to limit spread. Strict adherence to infection control precautions was essential in containing outbreaks. In addition, grouping patients into cohorts and limiting access to SARS patients minimized exposure opportunities. Given the difficulty in implementing several of these measures, controls were frequently adapted to the acuity of SARS care and level of transmission within facilities. Although these conclusions are based only on a retrospective analysis of events, applying the experiences of Toronto and Taiwan to SARS preparedness planning efforts will likely minimize future transmission within healthcare facilities.",2004 May,"['McDonald, L. Clifford', 'Simor, Andrew E.', 'Su, Ih-Jen', 'Maloney, Susan', 'Ofner, Marianna', 'Chen, Kow-Tong', 'Lando, James F.', 'McGeer, Allison', 'Lee, Min-Ling', 'Jernigan, Daniel B.']",Emerg Infect Dis,,,True
94b5bb85c872c0c1db0148b572b78e82f284cf59,PMC,"Long-term SARS Coronavirus Excretion from Patient Cohort, China",http://dx.doi.org/10.3201/eid1010.040297,PMC3323244,15504274,NO-CC CODE,"This study investigated the long-term excretion of severe acute respiratory syndrome–associated coronavirus in sputum and stool specimens from 56 infected patients. The median (range) duration of virus excretion in sputa and stools was 21 (14–52) and 27 (16–126) days, respectively. Coexisting illness or conditions were associated with longer viral excretion in stools.",2004 Oct,"['Liu, Wei', 'Tang, Fang', 'Fontanet, Arnaud', 'Zhan, Lin', 'Zhao, Qiu-Min', 'Zhang, Pan-He', 'Wu, Xiao-Ming', 'Zuo, Shu-Qing', 'Baril, Laurence', 'Vabret, Astrid', 'Xin, Zhong-Tao', 'Shao, Yi-Ming', 'Yang, Hong', 'Cao, Wu-Chun']",Emerg Infect Dis,,,True
4dcc4cda564c914e44c9a3dd9e3d379b1e8cbb91,PMC,"Correction, vol. 10, no. 9",http://dx.doi.org/10.3201/eid1010.C11010,PMC3323253,,NO-CC CODE,,2004 Oct,,Emerg Infect Dis,,,True
80d9d5734676b9a27d165dbb2826d4ba1da23da5,PMC,Virus-specific RNA and Antibody from Convalescent-phase SARS Patients Discharged from Hospital,http://dx.doi.org/10.3201/eid1010.040026,PMC3323266,15504259,NO-CC CODE,"Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus (SARS-CoV). In a longitudinal cross-sectional study, we determined the prevalence of virus in bodily excretions and time of seroconversion in discharged patients with SARS. Conjunctival, throat, stool, and urine specimens were collected weekly from 64 patients and tested for SARS-CoV RNA by real-time polymerase chain reaction; serum samples were collected weekly and tested for SARS-CoV antibody with indirect enzyme immunoassay and immunofluorescence assay. In total, 126 conjunctival, 124 throat swab, 116 stool, and 124 urine specimens were analyzed. Five patients had positive stool samples, collected in weeks 5–9. Two patients seroconverted in weeks 7 and 8; the others were seropositive at the first serum sample collection. In this study, 5 (7.8%) of 64 patients continued to shed viral RNA in stool samples only, for up to week 8 of illness. Most seroconversions occurred by week 6 of illness.",2004 Oct,"['Leong, Hoe Nam', 'Chan, Kwai Peng', 'Khan, Ali S.', 'Oon, Lynette', 'Se-Thoe, Su Yun', 'Bai, Xin Lai', 'Yeo, Daniel', 'Leo, Yee Sin', 'Ang, Brenda', 'Ksiazek, Thomas G.', 'Ling, Ai Ee']",Emerg Infect Dis,,,True
76afb423879efd78bcd26ac2be9086727030f990,PMC,"Laboratory Diagnosis of Four Recent Sporadic Cases of Community-acquired SARS, Guangdong Province, China",http://dx.doi.org/10.3201/eid1010.040445,PMC3323270,15504263,NO-CC CODE,"Four cases of severe acute respiratory syndrome (SARS) that occurred from December 16, 2003, to January 8, 2004, in the city of Guangzhou, Guangdong Province, China, were investigated. Clinical specimens collected from these patients were tested by provincial and national laboratories in China as well as members of the World Health Organization SARS Reference and Verification Laboratory Network in a collaborative effort to identify and confirm SARS-associated coronavirus (SARS-CoV) infection. Although SARS-CoV was not isolated from any patient, specimens from three patients were positive for viral RNA by reverse transcription–polymerase chain reaction assay, and all patients had detectable rises in SARS-CoV–specific antibodies. This study shows the effectiveness of a collaborative, multilaboratory response to diagnose SARS.",2004 Oct,"['Liang, Guodong', 'Chen, Qiuxia', 'Xu, Jianguo', 'Liu, Yufei', 'Lim, Wilina', 'Peiris, J.S.M.', 'Anderson, Larry J.', 'Ruan, Li', 'Li, Hui', 'Kan, Biao', 'Di, Biao', 'Cheng, Peter', 'Chan, K.H.', 'Erdman, Dean D.', 'Gu, Shuyan', 'Yan, Xinge', 'Liang, Weili', 'Zhou, Duanhua', 'Haynes, Lia', 'Duan, Shumin', 'Zhang, Xin', 'Zheng, Han', 'Gao, Yang', 'Tong, Suxiang', 'Li, Dexin', 'Fang, Ling', 'Qin, Pengzhe', 'Xu, Wenbo', None]",Emerg Infect Dis,,,True
c5557ff86a3d5630f341285081a5d39089964ab3,PMC,"SARS in Teaching Hospital, Taiwan",http://dx.doi.org/10.3201/eid1010.040356,PMC3323276,15515251,NO-CC CODE,,2004 Oct,"['Chen, Yee-Chun', 'Chen, Ming-Fong', 'Liu, Shuen-Zen', 'Romeis, James C.', 'Lee, Yuan-Teh']",Emerg Infect Dis,,,True
21bff37a6a0f9daebb9e37c4bb0937d642c39d12,PMC,New and Re-Emerging Infectious Diseases,http://dx.doi.org/10.3201/eid1010.040531,PMC3323277,,NO-CC CODE,,2004 Oct,"Docampo, Roberto",Emerg Infect Dis,,,False
a0f886e37b6c1b0dbce48aa05a6a7638368110d4,PMC,SARS Patients and Need for Treatment,http://dx.doi.org/10.3201/eid1010.040091,PMC3323283,15515244,NO-CC CODE,,2004 Oct,"['Chan, Johnny W.M.', 'Lee, Samuel']",Emerg Infect Dis,,,True
ce40c2d0956a6167604ab1a0955fd47f22b55111,PMC,SARS Coronavirus Detection,http://dx.doi.org/10.3201/eid1007.030678,PMC3323308,15324554,NO-CC CODE,"We developed a set of three real-time reverse transcription–polymerase chain reaction (PCR) assays that amplify three different regions of the SARS-associated coronavirus (SARS-CoV), can be run in parallel or in a single tube, and can detect <10 genome equivalents of SARS-CoV. The assays consider all currently available SARS-CoV sequences and are optimized for two prominent real-time PCR platforms.",2004 Jul,"['Nitsche, Andreas', 'Schweiger, Brunhilde', 'Ellerbrok, Heinz', 'Niedrig, Matthias', 'Pauli, Georg']",Emerg Infect Dis,,,True
85c624c0a20d8ed83f850072ce1e4bfdc197dedc,PMC,Psychosocial Impact of SARS,http://dx.doi.org/10.3201/eid1007.040090,PMC3323309,15338536,NO-CC CODE,,2004 Jul,"['Tsang, Hector W.H.', 'Scudds, Rhonda J.', 'Chan, Ellen Y.L.']",Emerg Infect Dis,,,True
4e97c78baf0d09de4207f0436d01db05826e5b20,PMC,Detection of SARS-associated Coronavirus in Throat Wash and Saliva in Early Diagnosis,http://dx.doi.org/10.3201/eid1007.031113,PMC3323313,15324540,NO-CC CODE,"The severe acute respiratory syndrome–associated coronavirus (SARS-CoV) is thought to be transmitted primarily through dispersal of droplets, but little is known about the load of SARS-CoV in oral droplets. We examined oral specimens, including throat wash and saliva, and found large amounts of SARS-CoV RNA in both throat wash (9.58 x 10(2) to 5.93 x 10(6) copies/mL) and saliva (7.08 x 10(3) to 6.38 x 10(8) copies/mL) from all specimens of 17 consecutive probable SARS case-patients, supporting the possibility of transmission through oral droplets. Immunofluorescence study showed replication of SARS-CoV in the cells derived from throat wash, demonstrating the possibility of developing a convenient antigen detection assay. This finding, with the high detection rate a median of 4 days after disease onset and before the development of lung lesions in four patients, suggests that throat wash and saliva should be included in sample collection guidelines for SARS diagnosis.",2004 Jul,"['Wang, Wei-Kung', 'Chen, Shey-Ying', 'Liu, I-Jung', 'Chen, Yee-Chun', 'Chen, Hui-Ling', 'Yang, Chao-Fu', 'Chen, Pei-Jer', 'Yeh, Shiou-Hwei', 'Kao, Chuan-Liang', 'Huang, Li-Min', 'Hsueh, Po-Ren', 'Wang, Jann-Tay', 'Sheng, Wang-Hwei', 'Fang, Chi-Tai', 'Hung, Chien-Ching', 'Hsieh, Szu-Min', 'Su, Chan-Ping', 'Chiang, Wen-Chu', 'Yang, Jyh-Yuan', 'Lin, Jih-Hui', 'Hsieh, Szu-Chia', 'Hu, Hsien-Ping', 'Chiang, Yu-Ping', 'Wang, Jin-Town', 'Yang, Pan-Chyr', 'Chang, Shan-Chwen', None, None]",Emerg Infect Dis,,,True
b62b8267bb53def16c93b7e566c780f7ab70456c,PMC,Human Metapneumovirus and Chronic Obstructive Pulmonary Disease,http://dx.doi.org/10.3201/eid1007.030633,PMC3323314,15338546,NO-CC CODE,,2004 Jul,"['Vicente, Diego', 'Montes, Milagrosa', 'Cilla, Gustavo', 'Pérez-Trallero, Emilio']",Emerg Infect Dis,,,True
bce2ef17ec8b6c4f09ea5db6941423ebacfaaa0f,PMC,Manual of Travel Medicine and Health,http://dx.doi.org/10.3201/eid1007.031004,PMC3323316,,NO-CC CODE,Manual of Travel Medicine and Health,2004 Jul,"Posey, Drew L.",Emerg Infect Dis,,,False
9d91b77a524dbfd635e4db011f1e9bfe84c55861,PMC,Mice Susceptible to SARS Coronavirus,http://dx.doi.org/10.3201/eid1007.031119,PMC3323317,15324552,NO-CC CODE,"Murine models of severe acute respiratory syndrome–associated coronavirus (SARS-CoV) will greatly advance research on this emerging virus. When BALB/c mice were simultaneously inoculated intranasally and orally, replication of SARS-CoV was found in both lung and intestinal tissue.",2004 Jul,"['Wentworth, David E.', 'Gillim-Ross, Laura', 'Espina, Noel', 'Bernard, Kristen A.']",Emerg Infect Dis,,,True
92d3b21a383e7937cc7e70bc0c1fbb4bf7c09b87,PMC,Syndromic Surveillance,http://dx.doi.org/10.3201/eid1007.031035,PMC3323334,15338541,NO-CC CODE,,2004 Jul,"['Dembek, Zygmunt F.', 'Cochrane, Dennis G.', 'Pavlin, Julie A.']",Emerg Infect Dis,,,True
24ff3659d783f4ae055ca1580b01d7f1ca36b9ab,PMC,Emerging Infections: What Have We Learned from SARS?,http://dx.doi.org/10.3201/eid1007.040166,PMC3323335,15338569,NO-CC CODE,,2004 Jul,"Galvani, Alison P.",Emerg Infect Dis,,,True
e5c898f447a574feb83e59b9c5dbb4deb1b267f0,PMC,Transporting Patient with Suspected SARS,http://dx.doi.org/10.3201/1007.030608,PMC3323337,15338533,NO-CC CODE,,2004 Jul,"['Tsai, Shin-Han', 'Tsang, Chiu-Man', 'Wu, Hsueh-Ru', 'Lu, Li-Hua', 'Pai, Yung-Chia', 'Olsen, Mark', 'Chiu, Wen-Ta']",Emerg Infect Dis,,,True
af8bd3576468e8c80a70d8ed5a07e4b2be7a6b80,PMC,Human Metapneumovirus and Severity of Respiratory Syncytial Virus Disease,http://dx.doi.org/10.3201/eid1007.030983,PMC3323339,15324559,NO-CC CODE,,2004 Jul,"['Lazar, Isaac', 'Weibel, Carla', 'Dziura, James', 'Ferguson, David', 'Landry, Marie L.', 'Kahn, Jeffrey S.']",Emerg Infect Dis,,,True
e69dfe25f7db4608216cabd383668302a49df586,PMC,Model Parameters and Outbreak Control for SARS,http://dx.doi.org/10.3201/eid1007.030647,PMC3323341,15324546,NO-CC CODE,"Control of the 2002–2003 severe acute respiratory syndrome (SARS) outbreak was based on rapid diagnosis coupled with effective patient isolation. We used uncertainty and sensitivity analysis of the basic reproductive number R(0) to assess the role that model parameters play in outbreak control. The transmission rate and isolation effectiveness have the largest fractional effect on R(0). We estimated the distribution of the reproductive number R(0) under perfect isolation conditions. The distribution lies in the interquartile range 0.19–1.08, with a median of 0.49. Even though the median of R(0) is <1, we found that 25% of our R(0) distribution lies at R(0) > 1, even with perfect isolation. This implies the need to simultaneously apply more than one method of control.",2004 Jul,"['Chowell, Gerardo', 'Castillo-Chavez, Carlos', 'Fenimore, Paul W.', 'Kribs-Zaleta, Christopher M.', 'Arriola, Leon', 'Hyman, James M.']",Emerg Infect Dis,,,True
a06b054ac060108a8563363fa40ce617eb7af258,PMC,"Environmental and Occupational Health Response to SARS, Taiwan, 2003",http://dx.doi.org/10.3201/eid1007.030728,PMC3323342,15324536,NO-CC CODE,Environmental and Occupational Health Industrial hygiene emergency response to SARS in Taiwan.,2004 Jul,"['Esswein, Eric J.', 'Kiefer, Max', 'Wallingford, Ken', 'Burr, Greg', 'Lee, Lukas Jyhun-Hsiarn', 'Wang, Jung-Der', 'Wang, Shun Chih', 'Su, Ih-Jen']",Emerg Infect Dis,,,True
91af6f5f54820a907d235b3d89cc5e94d3587aea,PMC,"SARS Control and Psychological Effects of Quarantine, Toronto, Canada",http://dx.doi.org/10.3201/eid1007.030703,PMC3323345,15324539,NO-CC CODE,"As a transmissible infectious disease, severe acute respiratory syndrome (SARS) was successfully contained globally by instituting widespread quarantine measures. Although these measures were successful in terminating the outbreak in all areas of the world, the adverse effects of quarantine have not previously been determined in a systematic manner. In this hypothesis-generating study supported by a convenience sample drawn in close temporal proximity to the period of quarantine, we examined the psychological effects of quarantine on persons in Toronto, Canada. The 129 quarantined persons who responded to a Web-based survey exhibited a high prevalence of psychological distress. Symptoms of posttraumatic stress disorder (PTSD) and depression were observed in 28.9% and 31.2% of respondents, respectively. Longer durations of quarantine were associated with an increased prevalence of PTSD symptoms. Acquaintance with or direct exposure to someone with a diagnosis of SARS was also associated with PTSD and depressive symptoms.",2004 Jul,"['Hawryluck, Laura', 'Gold, Wayne L.', 'Robinson, Susan', 'Pogorski, Stephen', 'Galea, Sandro', 'Styra, Rima']",Emerg Infect Dis,,,True
085f0b23abbdb47bd03b99b8476d56efb3d42492,PMC,Collecting Data To Assess SARS Interventions,http://dx.doi.org/10.3201/eid1007.030749,PMC3323351,15324551,NO-CC CODE,"With cases of severe acute respiratory syndrome (SARS) occurring across geographic regions, data collection on the effectiveness of intervention strategies should be standardized to facilitate analysis. We propose a minimum dataset to capture data needed to examine the basic reproduction rate, case status and criteria, symptoms, and outcomes of SARS.",2004 Jul,"['Scott, R. Douglas', 'Gregg, Edward', 'Meltzer, Martin I.']",Emerg Infect Dis,,,False
63b9deb2d4d45240dd29d2361481fb1f94830497,PMC,Collecting Data To Assess SARS Interventions,http://dx.doi.org/10.3201/eid1007.030749,PMC3323351,15324551,NO-CC CODE,"With cases of severe acute respiratory syndrome (SARS) occurring across geographic regions, data collection on the effectiveness of intervention strategies should be standardized to facilitate analysis. We propose a minimum dataset to capture data needed to examine the basic reproduction rate, case status and criteria, symptoms, and outcomes of SARS.",2004 Jul,"['Scott, R. Douglas', 'Gregg, Edward', 'Meltzer, Martin I.']",Emerg Infect Dis,,,False
ba57dd74c557de7638d8c30c1622de799edc65cd,PMC,Collecting Data To Assess SARS Interventions,http://dx.doi.org/10.3201/eid1007.030749,PMC3323351,15324551,NO-CC CODE,"With cases of severe acute respiratory syndrome (SARS) occurring across geographic regions, data collection on the effectiveness of intervention strategies should be standardized to facilitate analysis. We propose a minimum dataset to capture data needed to examine the basic reproduction rate, case status and criteria, symptoms, and outcomes of SARS.",2004 Jul,"['Scott, R. Douglas', 'Gregg, Edward', 'Meltzer, Martin I.']",Emerg Infect Dis,,,True
b1f59bdfada5dfed801691b8499168baf8b5c67f,PMC,SARS Molecular Detection External Quality Assurance,http://dx.doi.org/10.3201/eid1012.040416,PMC3323363,15663861,NO-CC CODE,"Inactivated severe acute respiratory syndrome–associated coronavirus samples were used for an external quality assurance study within the World Health Organization SARS Reference and Verification Network and other reference institutions. Of 58 participants, 51 correctly detected virus in all samples >9,400 RNA copies per milliliter and none in negative samples. Commercial test kits significantly improved the outcome.",2004 Dec,"['Drosten, Christian', 'Doerr, Hans Wilhelm', 'Lim, Wilina', 'Stöhr, Klaus', 'Niedrig, Matthias']",Emerg Infect Dis,,,True
342d06ebd07e4973d9825fb4767d43074949c022,PMC,"Historical, New, and Reemerging Links between Human and Animal Health",http://dx.doi.org/10.3201/eid1012.041037,PMC3323373,15717420,NO-CC CODE,,2004 Dec,"['Marano, Nina', 'Pappiaoanou, Marguerite']",Emerg Infect Dis,,,True
cd72303957519f8ec6ea7df1d21c1fd6c330fe90,PMC,Wildlife as Source of Zoonotic Infections,http://dx.doi.org/10.3201/eid1012.040707,PMC3323390,15663840,NO-CC CODE,"Zoonoses with a wildlife reservoir represent a major public health problem, affecting all continents. Hundreds of pathogens and many different transmission modes are involved, and many factors influence the epidemiology of the various zoonoses. The importance and recognition of wildlife as a reservoir of zoonoses are increasing. Cost-effective prevention and control of these zoonoses necessitate an interdisciplinary and holistic approach and international cooperation. Surveillance, laboratory capability, research, training and education, and communication are key elements.",2004 Dec,"['Kruse, Hilde', 'Kirkemo, Anne-Mette', 'Handeland, Kjell']",Emerg Infect Dis,,,True
53c202275d1fc7697460590ddb247e5675b661fa,PMC,Antibodies to SARS Coronavirus in Civets,http://dx.doi.org/10.3201/eid1012.040520,PMC3323399,15663874,NO-CC CODE,"Using three different assays, we examined 103 serum samples collected from different civet farms and a market in China in June 2003 and January 2004. While civets on farms were largely free from SARS-CoV infection, ≈80% of the animals from one animal market in Guangzhou contained significant levels of antibody to SARS-CoV, which suggests no widespread infection among civets resident on farms, and the infection of civets in the market might be associated with trading activities under the conditions of overcrowding and mixing of various animal species.",2004 Dec,"['Tu, Changchun', 'Crameri, Gary', 'Kong, Xiangang', 'Chen, Jinding', 'Sun, Yanwei', 'Yu, Meng', 'Xiang, Hua', 'Xia, Xianzhu', 'Liu, Shengwang', 'Ren, Tao', 'Yu, Yedong', 'Eaton, Bryan T.', 'Xuan, Hua', 'Wang, Lin-Fa']",Emerg Infect Dis,,,True
2d97940930d80363a94347a1356e4059a0b867d6,PMC,Topographic Changes in SARS Coronavirus–infected Cells at Late Stages of Infection,http://dx.doi.org/10.3201/eid1011.040195,PMC3328989,15550199,NO-CC CODE,"Scanning electron and atomic force microscopy was used for the first time to view the maturation of the severe acute respiratory syndrome–associated coronavirus at the cell surface. The surface form of the cells at advanced infection displayed prolific pseudopodia that, in addition to the rest of the plasma membrane, were also active sites of virus release. High magnification of the maturing virus particles showed a rosette appearance with short knoblike spikes under both the scanning electron and atomic force microscopes. The final expulsion step of the maturing virus particles seemed to result in some disruptions to the plasma membrane. The cytoskeletal network along the edge of the infected cells was enhanced and could be involved in transporting and expelling the progeny virus particles. Thickening of the actin filaments at the cell edge provided the bending force to extrude the virus particles.",2004 Nov,"['Ng, M.L.', 'Lee, J.W.M.', 'Leong, M.L.N.', 'Ling, A.-E.', 'Tan, H.-C.', 'Ooi, E.E.']",Emerg Infect Dis,,,True
0758be46dc2f4ada2905d557959a82ed31f0b93c,PMC,Nurses' Working Conditions: Implications for Infectious Disease,http://dx.doi.org/10.3201/eid1011.040253,PMC3328993,15550212,NO-CC CODE,Poor working conditions are associated with risk for occupational infections.,2004 Nov,"['Stone, Patricia W.', 'Clarke, Sean P.', 'Cimiotti, Jeannie', 'Correa-de-Araujo, Rosaly']",Emerg Infect Dis,,,True
4ea304eab3fcb728a21fb66f902c4c5d2a52ec2e,PMC,Nucleocapsid Protein as Early Diagnostic Marker for SARS,http://dx.doi.org/10.3201/eid1011.040516,PMC3329003,15550204,NO-CC CODE,"Serum samples from 317 patients with patients with severe acute respiratory syndrome (SARS) were tested for the nucleocapsid (N) protein of SARS-associated coronavirus, with sensitivities of 94% and 78% for the first 5 days and 6–10 days after onset, respectively. The specificity was 99.9%. N protein can be used as an early diagnostic maker for SARS.",2004 Nov,"['Che, Xiao-Yan', 'Hao, Wei', 'Wang, Yadi', 'Di, Biao', 'Yin, Kai', 'Xu, Yin-Chao', 'Feng, Chang-Sen', 'Wan, Zhuo-Yue', 'Cheng, Vincent C.C.', 'Yuen, Kwok-Yung']",Emerg Infect Dis,,,True
99c0958f9fa04d32dcdd13fcc01ffcb531f48950,PMC,"Plagues, Public Health, and Politics",http://dx.doi.org/10.3201/eid1011.040673,PMC3329042,16010727,NO-CC CODE,,2004 Nov,"['Koplan, Jeffrey P.', 'McPheeters, Melissa']",Emerg Infect Dis,,,True
affa4df43665fb042bffde141c288050aa99ed47,PMC,"Public Health Interventions and SARS Spread, 2003",http://dx.doi.org/10.3201/eid1011.040729,PMC3329045,15550198,NO-CC CODE,"The 2003 outbreak of severe acute respiratory syndrome (SARS) was contained largely through traditional public health interventions, such as finding and isolating case-patients, quarantining close contacts, and enhanced infection control. The independent effectiveness of measures to ""increase social distance"" and wearing masks in public places requires further evaluation. Limited data exist on the effectiveness of providing health information to travelers. Entry screening of travelers through health declarations or thermal scanning at international borders had little documented effect on detecting SARS cases; exit screening appeared slightly more effective. The value of border screening in deterring travel by ill persons and in building public confidence remains unquantified. Interventions to control global epidemics should be based on expert advice from the World Health Organization and national authorities. In the case of SARS, interventions at a country's borders should not detract from efforts to identify and isolate infected persons within the country, monitor or quarantine their contacts, and strengthen infection control in healthcare settings.",2004 Nov,"['Bell, David M.', None]",Emerg Infect Dis,,,True
e722ac6d3a3d6676a700214141cdead17950d590,PMC,Healthcare Settings as Amplifiers of Infectious Disease,http://dx.doi.org/10.3201/eid1011.040797_01,PMC3329047,16010741,NO-CC CODE,,2004 Nov,"['Chiarello, Linda A.', 'Tapper, Michael L.']",Emerg Infect Dis,,,False
96f00e294d684a5201ec5a5166724e39a21bf997,PMC,Transformation of the Developing World: Socioeconomic Matrix,http://dx.doi.org/10.3201/eid1011.040797_03,PMC3329049,16010742,NO-CC CODE,,2004 Nov,"['Carroll, Dennis', 'Gardner, Pierce', 'Kay, Bradford A.', 'Osterholm, Michael', 'Ryan, Edward T.']",Emerg Infect Dis,,,False
4d2aa0724ebf4c9ee99e18267c0b388e98f8b28b,PMC,Battling 21st-Century Scourges with a 14th-Century Toolbox,http://dx.doi.org/10.3201/eid1011.040797_12,PMC3329058,16010748,NO-CC CODE,,2004 Nov,"['Cetron, Martin', 'Simone, Pattie']",Emerg Infect Dis,,,False
3818785d389b05d37729f9229ebc60c20bd65eb2,PMC,Emerging Issues for the Public Health Laboratory,http://dx.doi.org/10.3201/eid1011.040797_13,PMC3329059,16010743,NO-CC CODE,,2004 Nov,"['Somsel, Patricia', 'Warnock, David']",Emerg Infect Dis,,,False
ca4c51d7b9ad3d31045bf31ec22e63c693691f5b,PMC,International Conference on Emerging Infectious Diseases,http://dx.doi.org/10.3201/eid1011.040857,PMC3329061,,NO-CC CODE,,2004 Nov,"['Tauxe, Robert V.', 'Khabbaz, Rima F.', 'Cameron, Daniel N.', 'Feinman, Lori']",Emerg Infect Dis,,,False
c7bc90f329faeba483338d68f8cda2b59506da57,PMC,Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen,http://dx.doi.org/10.1038/nature10996,PMC3350622,22504179,NO-CC CODE,"As with many other viruses, the initial cell attachment of rotaviruses, major causative agent of infantile gastroenteritis, is mediated by interactions with specific cellular glycans(1–4). The distally located VP8* domain of the rotavirus spike protein VP4(5) mediates such interactions. The existing paradigm is that ‘sialidase-sensitive’ animal rotavirus strains bind to glycans with terminal sialic acid (Sia), whereas ‘sialidase-insensitive’ human rotavirus (HR) strains bind to glycans with internal Sia such as GM1(3). Although the involvement of Sia in the animal strains is firmly supported by crystallographic studies(1,3,6,7), it is not yet known how VP8* of HRs interacts with Sia and whether their cell attachment necessarily involves sialoglycans. We found that VP8* of a HR strain specifically recognizes A-type histo-blood group antigen (HBGA) using a glycan array screen comprised of 511 glycans, and that virus infectivity in HT-29 cells is abrogated by anti-Atype antibodies as well as significantly enhanced in CHO cells genetically modified to express the A-type HBGA, providing a novel paradigm for initial cell attachment of HR. HBGAs are genetically determined glycoconjugates present in mucosal secretions, epithelial and on red blood cells(8), and are recognized as susceptibility and cell attachment factors for gastric pathogens like H. pylori(9) and noroviruses(10). Our crystallographic studies show that the A-type HBGA binds to the HR VP8* at the same location as the Sia in the VP8* of animal rotavirus, and suggest how subtle changes within the same structural framework allow for such receptor switching. These results raise the possibility that host susceptibility to specific HR strains and pathogenesis are influenced by genetically controlled expression of different HBGAs among the world’s population.",2012 Apr 15,"['Hu, Liya', 'Crawford, Sue E.', 'Czako, Rita', 'Cortes-Penfield, Nicolas W', 'Smith, David F.', 'Le Pendu, Jacques', 'Estes, Mary K.', 'Venkataram Prasad, B. V.']",Nature,,,True
782dc01012d45b7202ecb9f788a0234270077b47,PMC,Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen,http://dx.doi.org/10.1038/nature10996,PMC3350622,22504179,NO-CC CODE,"As with many other viruses, the initial cell attachment of rotaviruses, major causative agent of infantile gastroenteritis, is mediated by interactions with specific cellular glycans(1–4). The distally located VP8* domain of the rotavirus spike protein VP4(5) mediates such interactions. The existing paradigm is that ‘sialidase-sensitive’ animal rotavirus strains bind to glycans with terminal sialic acid (Sia), whereas ‘sialidase-insensitive’ human rotavirus (HR) strains bind to glycans with internal Sia such as GM1(3). Although the involvement of Sia in the animal strains is firmly supported by crystallographic studies(1,3,6,7), it is not yet known how VP8* of HRs interacts with Sia and whether their cell attachment necessarily involves sialoglycans. We found that VP8* of a HR strain specifically recognizes A-type histo-blood group antigen (HBGA) using a glycan array screen comprised of 511 glycans, and that virus infectivity in HT-29 cells is abrogated by anti-Atype antibodies as well as significantly enhanced in CHO cells genetically modified to express the A-type HBGA, providing a novel paradigm for initial cell attachment of HR. HBGAs are genetically determined glycoconjugates present in mucosal secretions, epithelial and on red blood cells(8), and are recognized as susceptibility and cell attachment factors for gastric pathogens like H. pylori(9) and noroviruses(10). Our crystallographic studies show that the A-type HBGA binds to the HR VP8* at the same location as the Sia in the VP8* of animal rotavirus, and suggest how subtle changes within the same structural framework allow for such receptor switching. These results raise the possibility that host susceptibility to specific HR strains and pathogenesis are influenced by genetically controlled expression of different HBGAs among the world’s population.",2012 Apr 15,"['Hu, Liya', 'Crawford, Sue E.', 'Czako, Rita', 'Cortes-Penfield, Nicolas W', 'Smith, David F.', 'Le Pendu, Jacques', 'Estes, Mary K.', 'Venkataram Prasad, B. V.']",Nature,,,False
cd69df65ac1b519f8032fcc29c7c2506094e0fcf,PMC,The great opportunity: Evolutionary applications to medicine and public health,http://dx.doi.org/10.1111/j.1752-4571.2007.00006.x,PMC3352398,25567489,NO-CC CODE,"Evolutionary biology is an essential basic science for medicine, but few doctors and medical researchers are familiar with its most relevant principles. Most medical schools have geneticists who understand evolution, but few have even one evolutionary biologist to suggest other possible applications. The canyon between evolutionary biology and medicine is wide. The question is whether they offer each other enough to make bridge building worthwhile. What benefits could be expected if evolution were brought fully to bear on the problems of medicine? How would studying medical problems advance evolutionary research? Do doctors need to learn evolution, or is it valuable mainly for researchers? What practical steps will promote the application of evolutionary biology in the areas of medicine where it offers the most? To address these questions, we review current and potential applications of evolutionary biology to medicine and public health. Some evolutionary technologies, such as population genetics, serial transfer production of live vaccines, and phylogenetic analysis, have been widely applied. Other areas, such as infectious disease and aging research, illustrate the dramatic recent progress made possible by evolutionary insights. In still other areas, such as epidemiology, psychiatry, and understanding the regulation of bodily defenses, applying evolutionary principles remains an open opportunity. In addition to the utility of specific applications, an evolutionary perspective fundamentally challenges the prevalent but fundamentally incorrect metaphor of the body as a machine designed by an engineer. Bodies are vulnerable to disease – and remarkably resilient – precisely because they are not machines built from a plan. They are, instead, bundles of compromises shaped by natural selection in small increments to maximize reproduction, not health. Understanding the body as a product of natural selection, not design, offers new research questions and a framework for making medical education more coherent. We conclude with recommendations for actions that would better connect evolutionary biology and medicine in ways that will benefit public health. It is our hope that faculty and students will send this article to their undergraduate and medical school Deans, and that this will initiate discussions about the gap, the great opportunity, and action plans to bring the full power of evolutionary biology to bear on human health problems.",2008 Feb,"['Nesse, Randolph M', 'Stearns, Stephen C']",Evol Appl,,,True
d086f62864fb6b39416bad3b5a969668b1791acb,PMC,Invasion thresholds and the evolution of nonequilibrium virulence,http://dx.doi.org/10.1111/j.1752-4571.2007.00003.x,PMC3352400,25567500,NO-CC CODE,"The enterprise of virulence management attempts to predict how social practices and other factors affect the evolution of parasite virulence. These predictions are often based on parasite optima or evolutionary equilibria derived from models of host-parasite dynamics. Yet even when such models accurately capture the parasite optima, newly invading parasites will typically not be at their optima. Here we show that parasite invasion of a host population can occur despite highly nonoptimal virulence. Fitness improvements soon after invasion may proceed through many steps with wide changes in virulence, because fitness depends on transmission as well as virulence, and transmission improvements can overwhelm nonoptimal virulence. This process is highly sensitive to mutation supply and the strength of selection. Importantly, the same invasion principle applies to the evolution of established parasites, whenever mutants arise that overcome host immunity/resistance. A host population may consequently experience repeated invasions of new parasite variants and possible large shifts in virulence as it evolves in an arms race with the parasite. An experimental study of phage lysis time and examples of mammalian viruses matching some of these characteristics are reviewed.",2008 Feb 9,"['Bull, James J', 'Ebert, Dieter']",Evol Appl,,,True
c275276d1cebcac93a5964d79f4b7174ed4afcf9,PMC,Evaluation of atherosclerotic lesions using dextran- and mannan–dextran-coated USPIO: MRI analysis and pathological findings,http://dx.doi.org/10.2147/IJN.S29417,PMC3356181,22619561,NO-CC CODE,"Magnetic resonance imaging (MRI) can detect atherosclerotic lesions containing accumulations of ultrasmall superparamagnetic iron oxides (USPIO). Positing that improved USPIO with a higher affinity for atherosclerotic plaques would yield better plaque images, we performed MRI and histologic studies to compare the uptake of dextran- and mannan–dextran-coated USPIO (D-USPIO and DM-USPIO, respectively) by the atherosclerotic walls of rabbits. We intravenously injected atherosclerotic rabbits with DM-USPIO (n = 5) or D-USPIO (n = 5). Two rabbits were the controls. The doses delivered were 0.08 (dose 1) (n = 1), 0.4 (dose 2) (n = 1), or 0.8 (dose 3) (n = 3) mmol iron/Kg. The dose 3 rabbits underwent in vivo contrast-enhanced magnetic resonance angiography (MRA) before and 5 days after USPIO administration. Afterwards, all animals were euthanized, the aortae were removed and subjected to in vitro MRI study. The signal-to-noise ratio (SNR) of the aortic wall in the same region of interest (ROI) was calculated in both in vivo and in vitro studies. Histological assessment through measurement of iron-positive regions in Prussian blue-stained specimens showed that iron-positive regions were significantly larger in rabbits injected with DM- rather than D-USPIO (P < 0.05) for all doses. In vivo MRA showed that the SNR-reducing effect of DM- was greater than that of D-USPIO (P < 0.05). With in vitro MRI scans, SNR was significantly lower in rabbits treated with dose 2 of DM-USPIO compared with D-USPIO treatment (P < 0.05), and it tended to be lower at dose 3 (P < 0.1). In conclusion, we suggest that DM-USPIO is superior to D-USPIO for the study of atherosclerotic lesions in rabbits.",2012 May 3,"['Tsuchiya, Keiko', 'Nitta, Norihisa', 'Sonoda, Akinaga', 'Nitta-Seko, Ayumi', 'Ohta, Shinichi', 'Takahashi, Masashi', 'Murata, Kiyoshi', 'Mukaisho, Kenichi', 'Shiomi, Masashi', 'Tabata, Yasuhiko', 'Nohara, Satoshi']",Int J Nanomedicine,,,True
cbe361acc62c98bc529a37614761fe15f49f0f95,PMC,A facile inhibitor screening of SARS coronavirus N protein using nanoparticle-based RNA oligonucleotide,http://dx.doi.org/10.2147/IJN.S31379,PMC3356205,22619553,NO-CC CODE,"Hundreds of million people worldwide have been infected with severe acute respiratory syndrome (SARS), and the rate of global death from SARS has remarkably increased. Hence, the development of efficient drug treatments for the biological effects of SARS is highly needed. We have previously shown that quantum dots (QDs)-conjugated RNA oligonucleotide is sensitive to the specific recognition of the SARS-associated coronavirus (SARS-CoV) nucleocapsid (N) protein. In this study, we found that a designed biochip could analyze inhibitors of the SARS-CoV N protein using nanoparticle-based RNA oligonucleotide. Among the polyphenolic compounds examined, (−)-catechin gallate and (−)-gallocatechin gallate demonstrated a remarkable inhibition activity on SARS-CoV N protein. (−)-catechin gallate and (−)-gallocatechin gallate attenuated the binding affinity in a concentrated manner as evidenced by QDs-conjugated RNA oligonucleotide on a designed biochip. At a concentration of 0.05 μg mL(−1), (−)-catechin gallate and (−)-gallocatechin gallate showed more than 40% inhibition activity on a nanoparticle-based RNA oligonucleotide biochip system.",2012 May 3,"Roh, Changhyun",Int J Nanomedicine,,,True
cbbf2c867d16605a4802dfeea0b9a2b21d8ccb47,PMC,"Screening for Influenza A(H1N1)pdm09, Auckland International Airport, New Zealand",http://dx.doi.org/10.3201/eid1805.111080,PMC3358051,22516105,NO-CC CODE,"Entry screening for influenza A(H1N1)pdm09 at Auckland International Airport, New Zealand, detected 4 cases, which were later confirmed, among 456,518 passengers arriving April 27–June 22, 2009. On the basis of national influenza surveillance data, which suggest that ≈69 infected travelers passed through the airport, sensitivity for screening was only 5.8%.",2012 May,"['Hale, Michael J.', 'Hoskins, Richard S.', 'Baker, Michael G.']",Emerg Infect Dis,,,True
0a492457fae69095f62bea0f3394665a4d83285c,PMC,"Coxsackievirus A21, Enterovirus 68, and Acute Respiratory Tract Infection, China",http://dx.doi.org/10.3201/eid1805.111376,PMC3358056,22516379,NO-CC CODE,"During August 2006–April 2010, in Beijing, China, 2 rare human enterovirus serotypes, coxsackievirus A21 and enterovirus 68, were detected most frequently in human enterovirus–positive adults with acute respiratory tract infections. Thus, during some years, these 2 viruses cause a substantial proportion of enterovirus-associated adult acute respiratory tract infections.",2012 May,"['Xiang, Zichun', 'Gonzalez, Richard', 'Wang, Zhong', 'Ren, Lili', 'Xiao, Yan', 'Li, Jianguo', 'Li, Yongjun', 'Vernet, Guy', 'Paranhos-Baccalà, Gláucia', 'Jin, Qi', 'Wang, Jianwei']",Emerg Infect Dis,,,True
022c31717b2ad8e7c25aab342d27c203d7e32527,PMC,Virulence Potential of Fusogenic Orthoreoviruses,http://dx.doi.org/10.3201/eid1806.111688,PMC3358160,22608100,NO-CC CODE,"Several severe respiratory virus infections that have emerged during the past decade originated in animals, including bats. In Indonesia, exposure to bats has been associated with increased risk of acquiring orthoreovirus infection. Although orthoreovirus infections are mild and self-limiting, we explored their potential for evolution into a more virulent form. We used conventional virus culture, electron microscopy, and molecular sequencing to isolate and identify orthoreoviruses from 3 patients in whom respiratory tract infection developed after travel to Indonesia. Virus characterization by plaque-reduction neutralization testing showed antigenic similarity, but sequencing of the small segment genes suggested virus reassortment, which could lead to increased virulence. Bats as a reservoir might contribute to virus evolution and genetic diversity, giving orthoreoviruses the potential to become more virulent. Evolution of this virus should be closely monitored so that prevention and control measures can be taken should it become more virulent.",2012 Jun,"['Wong, Ann H.', 'Cheng, Peter K.C.', 'Lai, Mary Y.Y.', 'Leung, Peter C.K.', 'Wong, Kitty K.Y.', 'Lee, W.Y.', 'Lim, Wilina W.L.']",Emerg Infect Dis,,,True
8d7876047a1709d32140730550bf5c1fa7808378,PMC,"Immunologic Changes during Pandemic (H1N1) 2009, China",http://dx.doi.org/10.3201/eid1706.100643,PMC3358185,21749768,NO-CC CODE,"We analyzed changes in immunologic values over time for 28 hospitalized patients with pandemic (H1N1) 2009. Levels of interleukin-6, interferon-γ, and interleukin-10 increased 1 day after illness onset and then decreased to baseline levels. Levels of virus-specific antibody were undetectable 1 day after illness onset and peaked 36 days later.",2011 Jun,"['Shen, Hong-Hui', 'Hou, Jun', 'Chen, Wei-Wei', 'Bai, Bing-Ke', 'Wang, Hai-Bin', 'Guo, Tong-Sheng', 'Liu, Ai-Xia', 'Li, Yong-Li', 'Zhao, Min', 'Mao, Pan-Yong', 'Li, Jin', 'Li, Bo-An', 'Mao, Yuan-Li']",Emerg Infect Dis,,,True
19bc8e320b35b2a9a0304aa51b5db76460b82137,PMC,Pandemic (H1N1) 2009 Risk for Frontline Health Care Workers,http://dx.doi.org/10.3201/eid1706.101030,PMC3358191,21749760,NO-CC CODE,"To determine whether frontline health care workers (HCWs) are at greater risk for contracting pandemic (H1N1) 2009 than nonclinical staff, we conducted a study of 231 HCWs and 215 controls. Overall, 79 (17.7%) of 446 had a positive antibody titer by hemagglutination inhibition, with 46 (19.9%) of 231 HCWs and 33 (15.3%) of 215 controls positive (OR 1.37, 95% confidence interval 0.84–2.22). Of 87 participants who provided a second serum sample, 1 showed a 4-fold rise in antibody titer; of 45 patients who had a nose swab sample taken during a respiratory illness, 7 had positive results. Higher numbers of children in a participant’s family and working in an intensive care unit were risk factors for infection; increasing age, working at hospital 2, and wearing gloves were protective factors. This highly exposed group of frontline HCWs was no more likely to contract pandemic (H1N1) 2009 influenza infection than nonclinical staff, which suggests that personal protective measures were adequate in preventing transmission.",2011 Jun,"['Marshall, Caroline', 'Kelso, Anne', 'McBryde, Emma', 'Barr, Ian G.', 'Eisen, Damon P.', 'Sasadeusz, Joe', 'Buising, Kirsty', 'Cheng, Allen C.', 'Johnson, Paul', 'Richards, Michael']",Emerg Infect Dis,,,True
b2afa8848026171f770c7154e8ff44c432ca23b7,PMC,"Coronavirus HKU1 in Children, Brazil, 1995",http://dx.doi.org/10.3201/eid1706.101381,PMC3358201,21749800,NO-CC CODE,,2011 Jun,"['Góes, Luiz G.', 'Durigon, Edison L.', 'Campos, Angélica A.', 'Hein, Noely', 'Passos, Saulo D.', 'Jerez, José A.']",Emerg Infect Dis,,,True
d2e50891500031a482f95969c3657a6ef253b22a,PMC,Social Factors Associated with AIDS and SARS,http://dx.doi.org/10.3201/eid1111.050424,PMC3367336,16318735,NO-CC CODE,We conducted a survey of 928 New York City area residents to assess knowledge and worry about AIDS and SARS. Specific sociodemographic groups of persons were more likely to be less informed and more worried about contracting the diseases.,2005 Nov,"['Des Jarlais, Don C.', 'Stuber, Jennifer', 'Tracy, Melissa', 'Tross, Susan', 'Galea, Sandro']",Emerg Infect Dis,,,True
a6fe0efaddf824480cd89f3940ad0109e74453b6,PMC,Quarantine Stressing Voluntary Compliance,http://dx.doi.org/10.3201/eid1111.050661,PMC3367339,16318738,NO-CC CODE,"A 1-day table-top exercise in San Diego, California, in December 2004 emphasized voluntary compliance with home quarantine to control an emerging infectious disease outbreak. The exercise heightened local civilian-military collaboration in public health emergency management. Addressing concerns about lost income by residents in quarantine was particularly challenging.",2005 Nov,"['DiGiovanni, Cleto', 'Bowen, Nancy', 'Ginsberg, Michele', 'Giles, Gregory']",Emerg Infect Dis,,,True
6e771d40d5f81b24dbf7ca95bd6f86538790f9ae,PMC,"Respiratory Infections during SARS Outbreak, Hong Kong, 2003",http://dx.doi.org/10.3201/eid1111.050729,PMC3367357,16318726,NO-CC CODE,The effect of community hygienic measures during the outbreak of severe acute respiratory syndrome in Hong Kong was studied by comparing the proportion of positive specimens of various respiratory viruses in 2003 with those from 1998 to 2002. Community hygienic measures significantly reduced the incidence of various respiratory viral infections.,2005 Nov,"['Lo, Janice Y.C.', 'Tsang, Thomas H.F.', 'Leung, Yiu-Hong', 'Yeung, Eugene Y.H.', 'Wu, Thomson', 'Lim, Wilina W.L.']",Emerg Infect Dis,,,True
7dec79b2d676d371ae0a82d32862aa59e5040870,PMC,Neutralizing Antibody Response and SARS Severity,http://dx.doi.org/10.3201/eid1111.040659,PMC3367364,16318725,NO-CC CODE,"Using the Taiwan nationwide laboratory-confirmed severe acute respiratory syndrome (SARS) database, we analyzed neutralizing antibody in relation to clinical outcomes. With a linear mixed model, neutralizing antibody titer was shown to peak between week 5 and week 8 after onset and to decline thereafter, with a half-life of 6.4 weeks. Patients with a longer illness showed a lower neutralizing antibody response than patients with a shorter illness duration (p = 0.008). When early responders were compared with most patients, who seroconverted on and after week 3 of illness, the small proportion (17.4%) of early responders (antibody detectable within 2 weeks) had a higher death rate (29.6% vs. 7.8%) (Fisher exact test, p = 0.004), had a shorter survival time of <2 weeks (Fisher exact test, p = 0.013), and were more likely to be > 60 years of age (Fisher exact test, p = 0.01). Our findings have implications for understanding the pathogenesis of SARS and for SARS vaccine research and development.",2005 Nov,"['Ho, Mei-Shang', 'Chen, Wei-Ju', 'Chen, Hour-Young', 'Lin, Szu-Fong', 'Wang, Min-Chin', 'Di, Jiali', 'Lu, Yen-Ta', 'Liu, Ching-Lung', 'Chang, Shan-Chwen', 'Chao, Chung-Liang', 'King, Chwan-Chuen', 'Chiou, Jeng-Min', 'Su, Ih-Jen', 'Yang, Jyh-Yuan']",Emerg Infect Dis,,,True
4519b7e7baeb12b34da4f55870d0000f6233f8d7,PMC,Microbe: Are We Ready for the Next Plague?,http://dx.doi.org/10.3201/eid1111.051084,PMC3367366,,NO-CC CODE,,2005 Nov,"Jahrling, Peter B.",Emerg Infect Dis,,,False
078025b470595541bbb492b1aaed90862cdca287,PMC,Antimicrobial Resistance Determinants and Future Control,http://dx.doi.org/10.3201/eid1106.050167,PMC3367590,15963271,NO-CC CODE,"At the beginning of the 21st century, antimicrobial resistance is common, has developed against every class of antimicrobial drug, and appears to be spreading into new clinical niches. We describe determinants likely to influence the future epidemiology and health impact of antimicrobial-resistant infections. Understanding these factors will ultimately optimize preventive strategies for an unpredictable future.",2005 Jun,"['Harbarth, Stephan', 'Samore, Matthew H.']",Emerg Infect Dis,,,True
5f35a51b9aed0111281ff79055d7566d6ef6c1c7,PMC,"Bushmeat Hunting, Deforestation, and Prediction of Zoonotic Disease",http://dx.doi.org/10.3201/eid1112.040789,PMC3367616,16485465,NO-CC CODE,"Understanding the emergence of new zoonotic agents requires knowledge of pathogen biodiversity in wildlife, human-wildlife interactions, anthropogenic pressures on wildlife populations, and changes in society and human behavior. We discuss an interdisciplinary approach combining virology, wildlife biology, disease ecology, and anthropology that enables better understanding of how deforestation and associated hunting leads to the emergence of novel zoonotic pathogens.",2005 Dec,"['Wolfe, Nathan D.', 'Daszak, Peter', 'Kilpatrick, A. Marm', 'Burke, Donald S.']",Emerg Infect Dis,,,True
b2eb07b13c059c3bc0907d5e3f38424dcd7fcd84,PMC,Viral Load Distribution in SARS Outbreak,http://dx.doi.org/10.3201/eid1112.040949,PMC3367618,16485474,NO-CC CODE,"An unprecedented community outbreak of severe acute respiratory syndrome (SARS) occurred in the Amoy Gardens, a high-rise residential complex in Hong Kong. Droplet, air, contaminated fomites, and rodent pests have been proposed to be mechanisms for transmitting SARS in a short period. We studied nasopharyngeal viral load of SARS patients on admission and their geographic distribution. Higher nasopharyngeal viral load was found in patients living in adjacent units of the same block inhabited by the index patient, while a lower but detectable nasopharyngeal viral load was found in patients living further away from the index patient. This pattern of nasopharyngeal viral load suggested that airborne transmission played an important part in this outbreak in Hong Kong. Contaminated fomites and rodent pests may have also played a role.",2005 Dec,"['Chu, Chung-Ming', 'Cheng, Vincent C.C.', 'Hung, Ivan F.N.', 'Chan, Kin-Sang', 'Tang, Bone S.F.', 'Tsang, Thomas H.F.', 'Chan, Kwok-Hung', 'Yuen, Kwok-Yung']",Emerg Infect Dis,,,True
fc9f4ba0a657fb6fe7c562097f43162406151a7e,PMC,SARS-CoV Infection in a Restaurant from Palm Civet,http://dx.doi.org/10.3201/eid1112.041293,PMC3367621,16485471,NO-CC CODE,"Epidemiologic investigations showed that 2 of 4 patients with severe acute respiratory syndrome (SARS) identified in the winter of 2003–2004 were a waitress at a restaurant in Guangzhou, China, that served palm civets as food and a customer who ate in the restaurant a short distance from animal cages. All 6 palm civets at the restaurant were positive for SARS-associated coronavirus (SARS-CoV). Partial spike (S) gene sequences of SARS-CoV from the 2 patients were identical to 4 of 5 S gene viral sequences from palm civets. Phylogenetic analysis showed that SARS-CoV from palm civets in the restaurant was most closely related to animal isolates. SARS cases at the restaurant were the result of recent interspecies transfer from the putative palm civet reservoir, and not the result of continued circulation of SARS-CoV in the human population.",2005 Dec,"['Wang, Ming', 'Yan, Meiying', 'Xu, Huifang', 'Liang, Weili', 'Kan, Biao', 'Zheng, Bojian', 'Chen, Honglin', 'Zheng, Han', 'Xu, Yanmei', 'Zhang, Enmin', 'Wang, Hongxia', 'Ye, Jingrong', 'Li, Guichang', 'Li, Machao', 'Cui, Zhigang', 'Liu, Yu-Fei', 'Guo, Rong-Tong', 'Liu, Xiao-Ning', 'Zhan, Liu-Hua', 'Zhou, Duan-Hua', 'Zhao, Ailan', 'Hai, Rong', 'Yu, Dongzhen', 'Guan, Yi', 'Xu, Jianguo']",Emerg Infect Dis,,,True
9a5a8345c449ca529d68c57e0b52b8f90b1297bd,PMC,Community Epidemiology Framework for Classifying Disease Threats,http://dx.doi.org/10.3201/eid1112.050306,PMC3367628,16485464,NO-CC CODE,"Recent evidence suggests that most parasites can infect multiple host species and that these are primarily responsible for emerging infectious disease outbreaks in humans and wildlife. However, the ecologic and evolutionary factors that constrain or facilitate such emergences are poorly understood. We propose a conceptual framework based on the pathogen's between- and within-species transmission rates to describe possible configurations of a multihost-pathogen community that may lead to disease emergence. We establish 3 dynamic thresholds separating 4 classes of disease outcomes, spillover, apparent multihost, true multihost, and potential emerging infectious disease; describe possible disease emergence scenarios; outline the population dynamics of each case; and clarify existing terminology. We highlight the utility of this framework with examples of disease threats in human and wildlife populations, showing how it allows us to understand which ecologic factors affect disease emergence and predict the impact of host shifts in a range of disease systems.",2005 Dec,"['Fenton, Andy', 'Pedersen, Amy B.']",Emerg Infect Dis,,,True
9f290aa8269c9b4f281f2e0757e22a4a72ac867d,PMC,Porcine Noroviruses Related to Human Noroviruses,http://dx.doi.org/10.3201/eid1112.050485,PMC3367634,16485473,NO-CC CODE,"Detection of genogroup II (GII) norovirus (NoV) RNA from adult pigs in Japan and Europe and GII NoV antibodies in US swine raises public health concerns about zoonotic transmission of porcine NoVs to humans, although no NoVs have been detected in US swine. To detect porcine NoVs and to investigate their genetic diversity and relatedness to human NoVs, 275 fecal samples from normal US adult swine were screened by reverse transcription–polymerase chain reaction with calicivirus universal primers. Six samples were positive for NoV. Based on sequence analysis of 3 kb on the 3´ end of 5 porcine NoVs, 3 genotypes in GII and a potential recombinant were identified. One genotype of porcine NoVs was genetically and antigenically related to human NoVs and replicated in gnotobiotic pigs. These results raise concerns of whether subclinically infected adult swine may be reservoirs of new human NoVs or if porcine/human GII recombinants could emerge.",2005 Dec,"['Wang, Qiu-Hong', 'Han, Myung Guk', 'Cheetham, Sonia', 'Souza, Menira', 'Funk, Julie A.', 'Saif, Linda J.']",Emerg Infect Dis,,,True
62ed08b25033369488b34d3a7aaee0401a3c00a0,PMC,Host Range and Emerging and Reemerging Pathogens,http://dx.doi.org/10.3201/eid1112.050997,PMC3367654,16485468,NO-CC CODE,"An updated literature survey identified 1,407 recognized species of human pathogen, 58% of which are zoonotic. Of the total, 177 are regarded as emerging or reemerging. Zoonotic pathogens are twice as likely to be in this category as are nonzoonotic pathogens. Emerging and reemerging pathogens are not strongly associated with particular types of nonhuman hosts, but they are most likely to have the broadest host ranges. Emerging and reemerging zoonoses are associated with a wide range of drivers, but changes in land use and agriculture and demographic and societal changes are most commonly cited. However, although zoonotic pathogens do represent the most likely source of emerging and reemerging infectious disease, only a small minority have proved capable of causing major epidemics in the human population.",2005 Dec,"['Woolhouse, Mark E.J.', 'Gowtage-Sequeria, Sonya']",Emerg Infect Dis,,,True
62e527f27449e1100ffd912c29df0b72b964fe97,PMC,"Behind the Mask: How the World Survived SARS, the First Epidemic of the 21st Century",http://dx.doi.org/10.3201/eid1112.051058,PMC3367656,,NO-CC CODE,,2005 Dec,"Massoudi, Mehran S.",Emerg Infect Dis,,,False
d9d6c6f034dd3114696c0811a672bbd5c9c9dc18,PMC,Role of Multisector Partnerships in Controlling Emerging Zoonotic Diseases,http://dx.doi.org/10.3201/eid1112.051322,PMC3367657,22289146,NO-CC CODE,,2005 Dec,"['Marano, Nina', 'Arguin, Paul', 'Pappaioanou, Marguerite', 'King, Lonnie']",Emerg Infect Dis,,,True
e400309a9601ccd52d0fbee511e868dfed9acef0,PMC,"Empyema in spinal canal in thoracic region, abscesses in paravertebral space, spondylitis: in clinical course of zoonosis Erysipelothrix rhusiopathiae",http://dx.doi.org/10.1007/s00586-012-2289-9,PMC3369048,22526696,NO-CC CODE,"OBJECTIVES: Erysipelas is an animal disease caused by Gram-positive bacteria Erysipelothrix rhusiopathiae. Among the domestic animals, domestic pig (Sus scrofa f. domestica) suffers most frequently from the disease in human environment. This is a typical animal-borne disease observed mainly in occupational groups employed in agriculture, farming (of animals and birds), fishing and manufacturing industry. METHODS: We are presenting the clinical course of infection (E. rhusiopathiae) and discuss clinical forms. E. rhusiopathiae in humans may have the following clinical course: mild form of skin infection diagnosed as local erythema (erysipeloid), disseminated form of skin infection and the most serious form of infection of systemic course (endocarditis and sepsis). Mild skin infection and local erythema are the most common forms. Very rare case of animal-borne infection course has been presented in which after initial phase the disease was generalised to the abscesses formation in paravertebral space, spondylitis and empyema formation in spinal canal. In the presented clinical case, the patient was suffering from diabetes. It was probably an additional risk factor of the disease generalisation. Patient underwent drainage of empyema in spinal canal, after which his neurological status gradually improved. Antibiotic therapy was implemented and continued for 8 weeks. Such course of erysipelas was not previously described in the literature. RESULTS: After therapy neurological status was improved. In follow MRI control exam empyema and spondylitis was successfully eliminated. CONCLUSIONS: Various complications of the disease, such as endocarditis and heart valves disturbances, are well known and are the most severe complications of the generalised infection. Proper targeted and long-term antibiotic therapy is crucial.",2012 Jun 17,"['Andrychowski, Jarosław', 'Jasielski, Piotr', 'Netczuk, Tomasz', 'Czernicki, Zbigniew']",Eur Spine J,,,True
8f0e06be9f6ded0251683770d5f9fa0efd15510b,PMC,Occupational Deaths among Healthcare Workers,http://dx.doi.org/10.3201/eid1107.041038,PMC3371777,16022771,NO-CC CODE,"Recent experiences with severe acute respiratory syndrome and the US smallpox vaccination program have demonstrated the vulnerability of healthcare workers to occupationally acquired infectious diseases. However, despite acknowledgment of risk, the occupational death rate for healthcare workers is unknown. In contrast, the death rate for other professions with occupational risk, such as police officer or firefighter, has been well defined. With available information from federal sources and calculating the additional number of deaths from infection by using data on prevalence and natural history, we estimate the annual death rate for healthcare workers from occupational events, including infection, is 17–57 per 1 million workers. However, a much more accurate estimate of risk is needed. Such information could inform future interventions, as was seen with the introduction of safer needle products. This information would also heighten public awareness of this often minimized but essential aspect of patient care.",2005 Jul,"['Sepkowitz, Kent A.', 'Eisenberg, Leon']",Emerg Infect Dis,,,True
43c97885b9857b19786fed791ef44c801ed5c97b,PMC,Veillonella montpellierensis Endocarditis,http://dx.doi.org/10.3201/eid1107.041361,PMC3371781,16022792,NO-CC CODE,"Veillonella spp. rarely cause infections in humans. We report a case of Veillonella endocarditis documented by isolating a slow-growing, gram-negative microbe in blood cultures. This microbe was identified as the newly recognized species Veillonella montpellierensis (100% homology) by 16S RNA gene sequence analysis.",2005 Jul,"['Rovery, Clarisse', 'Etienne, Anne', 'Foucault, Cédric', 'Berger, Pierre', 'Brouqui, Philippe']",Emerg Infect Dis,,,True
f8fd65777b69f5f9b7177a709e22607eb96abfa6,PMC,SARS Vaccine Development,http://dx.doi.org/10.3201/eid1107.050219,PMC3371787,16022774,NO-CC CODE,"Developing effective and safe vaccines is urgently needed to prevent infection by severe acute respiratory syndrome (SARS)–associated coronavirus (SARS-CoV). The inactivated SARS-CoV vaccine may be the first one available for clinical use because it is easy to generate; however, safety is the main concern. The spike (S) protein of SARS-CoV is the major inducer of neutralizing antibodies, and the receptor-binding domain (RBD) in the S1 subunit of S protein contains multiple conformational neutralizing epitopes. This suggests that recombinant proteins containing RBD and vectors encoding the RBD sequence can be used to develop safe and effective SARS vaccines.",2005 Jul,"['Jiang, Shibo', 'He, Yuxian', 'Liu, Shuwen']",Emerg Infect Dis,,,True
d0610fbc985c67974c9182498173b3b91c176072,PMC,SARS Coronavirus Detection Methods,http://dx.doi.org/10.3201/eid1107.041045,PMC3371792,16022791,NO-CC CODE,"Using clinical samples from patients with severe acute respiratory syndrome, we showed that the sensitivities of a quantitative reverse transcription–polymerase chain reaction (80% for fecal samples and 25% for urine samples) were higher than those of the polyclonal (50% and 5%) and monoclonal (35% and 8%) antibody-based nucleocapsid antigen capture enzyme-linked immunosorbent assays.",2005 Jul,"['Lau, Susanna K.P.', 'Che, Xiao-Yan', 'Woo, Patrick C.Y.', 'Wong, Beatrice H.L.', 'Cheng, Vincent C.C.', 'Woo, Gibson K.S.', 'Hung, Ivan F.N.', 'Poon, Rosana W.S.', 'Chan, Kwok-Hung', 'Peiris, J.S. Malik', 'Yuen, Kwok-Yung']",Emerg Infect Dis,,,True
9fa838a7ec9e083660848bf720e4d13d7d6f372f,PMC,"Asymptomatic SARS Coronavirus Infection among Healthcare Workers, Singapore",http://dx.doi.org/10.3201/eid1107.041165,PMC3371799,16022801,NO-CC CODE,"We conducted a study among healthcare workers (HCWs) exposed to patients with severe acute respiratory syndrome (SARS) before infection control measures were instituted. Of all exposed HCWs, 7.5% had asymptomatic SARS-positive cases. Asymptomatic SARS was associated with lower SARS antibody titers and higher use of masks when compared to pneumonic SARS.",2005 Jul,"['Wilder-Smith, Annelies', 'Teleman, Monica D.', 'Heng, Bee H.', 'Earnest, Arul', 'Ling, Ai E.', 'Leo, Yee S.']",Emerg Infect Dis,,,True
8baaa5e94c6ee9d9adbd29414dd001d31aefc269,PMC,Wildlife Trade and Global Disease Emergence,http://dx.doi.org/10.3201/eid1107.050194,PMC3371803,16022772,NO-CC CODE,"The global trade in wildlife provides disease transmission mechanisms that not only cause human disease outbreaks but also threaten livestock, international trade, rural livelihoods, native wildlife populations, and the health of ecosystems. Outbreaks resulting from wildlife trade have caused hundreds of billions of dollars of economic damage globally. Rather than attempting to eradicate pathogens or the wild species that may harbor them, a practical approach would include decreasing the contact rate among species, including humans, at the interface created by the wildlife trade. Since wildlife marketing functions as a system of scale-free networks with major hubs, these points provide control opportunities to maximize the effects of regulatory efforts.",2005 Jul,"['Karesh, William B.', 'Cook, Robert A.', 'Bennett, Elizabeth L.', 'Newcomb, James']",Emerg Infect Dis,,,True
3208852c9234f3d7d415af376bdb22cdb95f5bba,PMC,"Emergency Department Response to SARS, Taiwan",http://dx.doi.org/10.3201/eid1107.040917,PMC3371807,16022782,NO-CC CODE,"How emergency departments of different levels and types cope with a large-scale contagious infectious disease is unclear. We retrospectively analyzed the response of 100 emergency departments regarding use of personal protective equipment (PPE) and implementation of infection control measures (ICMs) during the severe acute respiratory syndrome outbreak in Taiwan. Emergency department workers in large hospitals were more severely affected by the epidemic. Large hospitals or public hospitals were more likely to use respirators. Small hospitals implemented more restrictive ICMs. Most emergency departments provided PPE (80%) and implemented ICMs (66%) at late stages of the outbreak. Instructions to use PPE or ICMs more frequently originated by emergency department administrators. The difficulty of implementing ICMs was significantly negatively correlated with their effectiveness. Because ability to prepare for and respond to emerging infectious diseases varies among hospitals, grouping infectious patients in a centralized location in an early stage of infection may reduce the extent of epidemics.",2005 Jul,"['Chen, Wei-Kung', 'Wu, Hong-Dar Isaac', 'Lin, Cheng-Chieh', 'Cheng, Yi-Chang']",Emerg Infect Dis,,,True
efff85e4de5521d86c399aceb8ef44c55a7a1121,PMC,Primate-to-Human Retroviral Transmission in Asia,http://dx.doi.org/10.3201/eid1107.040957,PMC3371821,16022776,NO-CC CODE,"We describe the first reported transmission to a human of simian foamy virus (SFV) from a free-ranging population of nonhuman primates in Asia. The transmission of an exogenous retrovirus, SFV, from macaques (Macaca fascicularis) to a human at a monkey temple in Bali, Indonesia, was investigated with molecular and serologic techniques. Antibodies to SFV were detected by Western blotting of serum from 1 of 82 humans tested. SFV DNA was detected by nested polymerase chain reaction (PCR) from the blood of the same person. Cloning and sequencing of PCR products confirmed the virus's close phylogenetic relationship to SFV isolated from macaques at the same temple. This study raises concerns that persons who work at or live around monkey temples are at risk for infection with SFV.",2005 Jul,"['Jones-Engel, Lisa', 'Engel, Gregory A.', 'Schillaci, Michael A.', 'Rompis, Aida', 'Putra, Artha', 'Suaryana, Komang Gde', 'Fuentes, Agustin', 'Beer, Brigitte', 'Hicks, Sarah', 'White, Robert', 'Wilson, Brenda', 'Allan, Jonathan S.']",Emerg Infect Dis,,,True
44ca543f5528ca4d7b33b401623cc1bf0afb84c6,PMC,Potential Impact of Antiviral Drug Use during Influenza Pandemic,http://dx.doi.org/10.3201/eid1109.041344,PMC3371825,16229762,NO-CC CODE,"The recent spread of highly pathogenic strains of avian influenza has highlighted the threat posed by pandemic influenza. In the early phases of a pandemic, the only treatment available would be neuraminidase inhibitors, which many countries are considering stockpiling for pandemic use. We estimate the effect on hospitalization rates of using different antiviral stockpile sizes to treat infection. We estimate that stockpiles that cover 20%–25% of the population would be sufficient to treat most of the clinical cases and could lead to 50% to 77% reductions in hospitalizations. Substantial reductions in hospitalization could be achieved with smaller antiviral stockpiles if drugs are reserved for persons at high risk.",2005 Sep,"['Gani, Raymond', 'Hughes, Helen', 'Fleming, Douglas', 'Griffin, Thomas', 'Medlock, Jolyon', 'Leach, Steve']",Emerg Infect Dis,,,True
55ffdd0f4c113e59ddf3ae633d00fb676abff48d,PMC,Emerging Infections and Pregnancy,http://dx.doi.org/10.3201/eid1211.060152,PMC3372330,17283611,NO-CC CODE,"A key component of the response to emerging infections is consideration of special populations, including pregnant women. Successful pregnancy depends on adaptation of the woman's immune system to tolerate a genetically foreign fetus. Although the immune system changes are not well understood, a shift from cell-mediated immunity toward humoral immunity is believed to occur. These immunologic changes may alter susceptibility to and severity of infectious diseases in pregnant women. For example, pregnancy may increase susceptibility to toxoplasmosis and listeriosis and may increase severity of illness and increase mortality rates from influenza and varicella. Compared with information about more conventional disease threats, information about emerging infectious diseases is quite limited. Pregnant women's altered response to infectious diseases should be considered when planning a response to emerging infectious disease threats.",2006 Nov,"['Jamieson, Denise J.', 'Theiler, Regan N.', 'Rasmussen, Sonja A.']",Emerg Infect Dis,,,True
e85838ff5bf9ad259d3511d9e906950e9d0d1ede,PMC,"Chikungunya Fever, Hong Kong",http://dx.doi.org/10.3201/eid1211.060574,PMC3372348,17283640,NO-CC CODE,,2006 Nov,"['Lee, Nelson', 'Wong, Chun K.', 'Lam, Wai Y.', 'Wong, Ann', 'Lim, Wilina', 'Lam, Christopher W.K.', 'Cockram, Clive S.', 'Sung, Joseph J.Y.', 'Chan, Paul K.S.', 'Tang, Julian W.']",Emerg Infect Dis,,,True
ef5660b91f755b280e59a60c59ea2eee570ee370,PMC,Prophylaxis and Treatment of Pregnant Women for Emerging Infections and Bioterrorism Emergencies,http://dx.doi.org/10.3201/eid1211.060618,PMC3372351,17283610,NO-CC CODE,"Emerging infectious disease outbreaks and bioterrorism attacks warrant urgent public health and medical responses. Response plans for these events may include use of medications and vaccines for which the effects on pregnant women and fetuses are unknown. Healthcare providers must be able to discuss the benefits and risks of these interventions with their pregnant patients. Recent experiences with outbreaks of severe acute respiratory syndrome, monkeypox, and anthrax, as well as response planning for bioterrorism and pandemic influenza, illustrate the challenges of making recommendations about treatment and prophylaxis for pregnant women. Understanding the physiology of pregnancy, the factors that influence the teratogenic potential of medications and vaccines, and the infection control measures that may stop an outbreak will aid planners in making recommendations for care of pregnant women during large-scale infectious disease emergencies.",2006 Nov,"['Cono, Joanne', 'Cragan, Janet D.', 'Jamieson, Denise J.', 'Rasmussen, Sonja A.']",Emerg Infect Dis,,,True
67946abf87640b5b9106aaaf732c11e4b7b07a28,PMC,Food Markets with Live Birds as Source of Avian Influenza,http://dx.doi.org/10.3201/eid1211.060675,PMC3372357,17283635,NO-CC CODE,,2006 Nov,"['Wang, Ming', 'Di, Biao', 'Zhou, Duan-Hua', 'Zheng, Bo-Jian', 'Jing, Huaiqi', 'Lin, Yong-Ping', 'Liu, Yu-Fei', 'Wu, Xin-Wei', 'Qin, Peng-Zhe', 'Wang, Yu-Lin', 'Jian, Li-Yun', 'Li, Xiang-Zhong', 'Xu, Jian-Xiong', 'Lu, En-Jie', 'Li, Tie-Gang', 'Xu, Jianguo']",Emerg Infect Dis,,,True
b8fc960573a817a8bdd0dc42420ef61f3073330d,PMC,Screening Laboratory Requests,http://dx.doi.org/10.3201/eid1211.060711,PMC3372359,17283641,NO-CC CODE,,2006 Nov,"['Petti, Cathy A.', 'Polage, Christopher R.', 'Hillyard, David R.']",Emerg Infect Dis,,,True
43fa93dd99dc6f9a8204dc22c79fb80ddb44dfba,PMC,"2,500-year Evolution of the Term Epidemic",http://dx.doi.org/10.3201/eid1206.051263,PMC3373038,16707055,NO-CC CODE,"The term epidemic (from the Greek epi [on] plus demos [people]), first used by Homer, took its medical meaning when Hippocrates used it as the title of one of his famous treatises. At that time, epidemic was the name given to a collection of clinical syndromes, such as coughs or diarrheas, occurring and propagating in a given period at a given location. Over centuries, the form and meaning of the term have changed. Successive epidemics of plague in the Middle Ages contributed to the definition of an epidemic as the propagation of a single, well-defined disease. The meaning of the term continued to evolve in the 19th-century era of microbiology. Its most recent semantic evolution dates from the last quarter of the 20th century, and this evolution is likely to continue in the future.",2006 Jun,"['Martin, Paul M.V.', 'Martin-Granel, Estelle']",Emerg Infect Dis,,,True
6dc8c0724577e0dc219ddb91ef0fc54569e56d37,PMC,"Human Streptococcus suis Outbreak, Sichuan, China",http://dx.doi.org/10.3201/eid1206.051194,PMC3373052,16707046,NO-CC CODE,"From mid-July to the end of August 2005, a total of 215 cases of human Streptococcus suis infections, 66 of which were laboratory confirmed, were reported in Sichuan, China. All infections occurred in backyard farmers who were directly exposed to infection during the slaughtering process of pigs that had died of unknown causes or been killed for food because they were ill. Sixty-one (28%) of the farmers had streptococcal toxic shock syndrome; 38 (62%) of them died. The other illnesses reported were sepsis (24%) and meningitis (48%) or both. All isolates tested positive for genes for tuf, species-specific 16S rRNA, cps2J, mrp, ef, and sly. A single strain of S. suis caused the outbreak, as shown by the identification of a single ribotype. The high death ratio was of concern; prohibiting backyard slaughtering ended the outbreak.",2006 Jun,"['Yu, Hongjie', 'Jing, Huaiqi', 'Chen, Zhihai', 'Zheng, Han', 'Zhu, Xiaoping', 'Wang, Hua', 'Wang, Shiwen', 'Liu, Lunguang', 'Zu, Rongqiang', 'Luo, Longze', 'Xiang, Nijuan', 'Liu, Honglu', 'Liu, Xuecheng', 'Shu, Yuelong', 'Lee, Shui Shan', 'Chuang, Shuk Kwan', 'Wang, Yu', 'Xu, Jianguo', 'Yang, Weizhong', None]",Emerg Infect Dis,,,True
c67b2bd9b0311fefe3b3d7371e01828fb248adfa,PMC,Coccidioidomycosis as a Common Cause of Community-acquired Pneumonia,http://dx.doi.org/10.3201/eid1206.060028,PMC3373055,16707052,NO-CC CODE,"The early manifestations of coccidioidomycosis (valley fever) are similar to those of other causes of community-acquired pneumonia (CAP). Without specific etiologic testing, the true frequency of valley fever may be underestimated by public health statistics. Therefore, we conducted a prospective observational study of adults with recent onset of a lower respiratory tract syndrome. Valley fever was serologically confirmed in 16 (29%) of 55 persons (95% confidence interval 16%–44%). Antimicrobial medications were used in 81% of persons with valley fever. Symptomatic differences at the time of enrollment had insufficient predictive value for valley fever to guide clinicians without specific laboratory tests. Thus, valley fever is a common cause of CAP after exposure in a disease-endemic region. If CAP develops in persons who travel or reside in Coccidioides-endemic regions, diagnostic evaluation should routinely include laboratory evaluation for this organism.",2006 Jun,"['Valdivia, Lisa', 'Nix, David', 'Wright, Mark', 'Lindberg, Elizabeth', 'Fagan, Timothy', 'Lieberman, Donald', ""Stoffer, T'Prien"", 'Ampel, Neil M.', 'Galgiani, John N.']",Emerg Infect Dis,,,True
f76e23d2dce15bbfa44c92cb917bf718ade1472e,PMC,Pets in Voluntary Household Quarantine,http://dx.doi.org/10.3201/eid1206.051548,PMC3373060,16752473,NO-CC CODE,,2006 Jun,"['Weese, J. Scott', 'Kruth, Stephen A.']",Emerg Infect Dis,,,True
5ca63d7cbf0377f09cb59fd81afbf751f9affef2,PMC,"Human Bocavirus Infection, Canada",http://dx.doi.org/10.3201/eid1205.051424,PMC3374420,16704852,NO-CC CODE,"Human Bocavirus was detected in 18 (1.5%) of 1,209 respiratory specimens collected in 2003 and 2004 in Canada. The main symptoms of affected patients were cough (78%), fever (67%), and sore throat (44%). Nine patients were hospitalized; of these, 8 (89%) were <5 years of age.",2006 May,"['Bastien, Nathalie', 'Brandt, Ken', 'Dust, Kerry', 'Ward, Diane', 'Li, Yan']",Emerg Infect Dis,,,True
1227edfb87826c52b770b469aaa2f41f5276cc84,PMC,Human Bocavirus in Children,http://dx.doi.org/10.3201/eid1205.051523,PMC3374421,16710957,NO-CC CODE,,2006 May,"['Foulongne, Vincent', 'Rodière, Michel', 'Segondy, Michel']",Emerg Infect Dis,,,True
01cfb2699f116b6a9e107c5eb20b1c5327d554f0,PMC,Biodefense Shield and Avian Influenza,http://dx.doi.org/10.3201/eid1205.051480,PMC3374437,16710964,NO-CC CODE,,2006 May,"['Alibek, Ken', 'Liu, Ge']",Emerg Infect Dis,,,True
607c9e39d3ba883da7c5796c4d102e74f87948b7,PMC,Coronavirus HKU1 Infection in the United States,http://dx.doi.org/10.3201/eid1205.051316,PMC3374449,16704837,NO-CC CODE,"In 2005, a new human coronavirus, HCoV-HKU1, was identified in Hong Kong. We screened respiratory specimens collected from December 16, 2001, to December 15, 2002, from children <5 years of age who tested negative for respiratory syncytial virus, parainfluenza viruses, influenza virus, and adenovirus for HCoV-HKU1 by reverse transcription–polymerase chain reaction. Overall, 1,048 respiratory specimens from 851 children were tested, and 9 HCoV-HKU1–positive children (1%) were identified, 2 of whom had 2 positive specimens. Children who had HCoV-HKU1 infection had evidence of either upper or lower respiratory tract infection or both. Two patients had disease beyond the respiratory tract. HCoV-HKU1 was identified from December 2001 to February 2002. Sequence analyses suggest that a single strain was circulating. HCoV-HKU1 is therefore likely circulating in the United States and is associated with upper and lower respiratory tract disease.",2006 May,"['Esper, Frank', 'Weibel, Carla', 'Ferguson, David', 'Landry, Marie L.', 'Kahn, Jeffrey S.']",Emerg Infect Dis,,,True
7e78314c36ae7c4c1c8caa99dd9d562d0c08f40f,PMC,"Human Bocavirus in Infants, New Zealand",http://dx.doi.org/10.3201/eid1311.070793,PMC3375780,18217577,NO-CC CODE,,2007 Nov,"['Redshaw, Natalie', 'Wood, Catherine', 'Rich, Fenella', 'Grimwood, Keith', 'Kirman, Joanna R.']",Emerg Infect Dis,,,True
ebed3cc5b0f4f9aa5a2dd3fd6f107c7a3a707914,PMC,Pandemic Influenza and Hospital Resources,http://dx.doi.org/10.3201/eid1311.070103,PMC3375786,18217556,NO-CC CODE,"Using estimates from the Centers for Disease Control and Prevention, the World Health Organization, and published models of the expected evolution of pandemic influenza, we modeled the surge capacity of healthcare facility and intensive care unit (ICU) requirements over time in northern Netherlands (≈1.7 million population). We compared the demands of various scenarios with estimates of maximum ICU capacity, factoring in healthcare worker absenteeism as well as reported and realistic estimates derived from semistructured telephone interviews with key management in ICUs in the study area. We show that even during the peak of the pandemic, most patients requiring ICU admission may be served, even those who have non–influenza-related conditions, provided that strong indications and decision-making rules are maintained for admission as well as for continuation (or discontinuation) of life support. Such a model should be integral to a preparedness plan for a pandemic with a new human-transmissible agent.",2007 Nov,"['Nap, Raoul E.', 'Andriessen, Maarten P.H.M.', 'Meessen, Nico E.L.', 'van der Werf, Tjip S.']",Emerg Infect Dis,,,True
f7eac9466807a50cfa24455c4a8b79bbf8c3510a,PMC,Conflict and Emerging Infectious Diseases,http://dx.doi.org/10.3201/eid1311.061093,PMC3375795,18217543,NO-CC CODE,"Detection and control of emerging infectious diseases in conflict situations are major challenges due to multiple risk factors known to enhance emergence and transmission of infectious diseases. These include inadequate surveillance and response systems, destroyed infrastructure, collapsed health systems and disruption of disease control programs, and infection control practices even more inadequate than those in resource-poor settings, as well as ongoing insecurity and poor coordination among humanitarian agencies. This article outlines factors that potentiate emergence and transmission of infectious diseases in conflict situations and highlights several priority actions for their containment and control.",2007 Nov,"['Gayer, Michelle', 'Legros, Dominique', 'Formenty, Pierre', 'Connolly, Maire A.']",Emerg Infect Dis,,,True
938700b6861f687bac83e4cc9fc056e7d38371de,PMC,Medical Students and Pandemic Influenza,http://dx.doi.org/10.3201/eid1311.070279,PMC3375803,18217571,NO-CC CODE,"To assess knowledge of pandemic influenza, we administered a questionnaire to all medical students at the University of Alberta; 354 (69%) of 510 students responded. Data from questionnaires such as this could help determine the role of medical students during a public health emergency.",2007 Nov,"['Herman, Benjamin', 'Rosychuk, Rhonda J.', 'Bailey, Tracey', 'Lake, Robert', 'Yonge, Olive', 'Marrie, Thomas J.']",Emerg Infect Dis,,,True
efac5c5025f1b54b65276fea345f3a2dc580d174,PMC,Retrospective Evaluation of Control Measures for Contacts of Patient with Marburg Hemorrhagic Fever,http://dx.doi.org/10.3201/eid1807.101638,PMC3376788,22710186,NO-CC CODE,"After an imported case of Marburg hemorrhagic fever was reported in 2008 in the Netherlands, control measures to prevent transmission were implemented. To evaluate consequences of these measures, we administered a structured questionnaire to 130 contacts classified as either having high-risk or low-risk exposure to body fluids of the case-patient; 77 (59.2%) of 130 contacts responded. A total of 67 (87.0%) of 77 respondents agreed that temperature monitoring and reporting was necessary, significantly more often among high-risk than low-risk contacts (p<0.001). Strict compliance with daily temperature monitoring decreased from 80.5% (62/77) during week 1 to 66.2% (51/77) during week 3. Contacts expressed concern about development of Marburg hemorrhagic fever (58.4%, 45/77) and infecting a family member (40.2%, 31/77). High-risk contacts had significantly higher scores on psychological impact scales (p<0.001) during and after the monitoring period. Public health authorities should specifically address consequences of control measures on the daily life of contacts.",2012 Jul,"['Timen, Aura', 'Isken, Leslie D.', 'Willemse, Patricia', 'van den Berkmortel, Franchette', 'Koopmans, Marion P.G.', 'van Oudheusden, Danielle E.C.', 'Bleeker-Rovers, Chantal P.', 'Brouwer, Annemarie E.', 'Grol, Richard P.T.M.', 'Hulscher, Marlies E.J.L.', 'van Dissel, Jaap T.']",Emerg Infect Dis,,,True
220b242a5251299e0effdd406a1fd6a08cf313c9,PMC,Spike Protein Fusion Peptide and Feline Coronavirus Virulence,http://dx.doi.org/10.3201/eid1807.120143,PMC3376813,22709821,NO-CC CODE,"Coronaviruses are well known for their potential to change their host or tissue tropism, resulting in unpredictable new diseases and changes in pathogenicity; severe acute respiratory syndrome and feline coronaviruses, respectively, are the most recognized examples. Feline coronaviruses occur as 2 pathotypes: nonvirulent feline enteric coronaviruses (FECVs), which replicate in intestinal epithelium cells, and lethal feline infectious peritonitis viruses (FIPVs), which replicate in macrophages. Evidence indicates that FIPV originates from FECV by mutation, but consistent distinguishing differences have not been established. We sequenced the full genome of 11 viruses of each pathotype and then focused on the single most distinctive site by additionally sequencing hundreds of viruses in that region. As a result, we identified 2 alternative amino acid differences in the putative fusion peptide of the spike protein that together distinguish FIPV from FECV in >95% of cases. By these and perhaps other mutations, the virus apparently acquires its macrophage tropism and spreads systemically.",2012 Jul,"['Chang, Hui-Wen', 'Egberink, Herman F.', 'Halpin, Rebecca', 'Spiro, David J.', 'Rottier, Peter J.M.']",Emerg Infect Dis,,,True
44217677cfbc7011d80be49e7087b539fe4fab0b,PMC,Timeliness of Nongovernmental versus Governmental Global Outbreak Communications,http://dx.doi.org/10.3201/eid1807.120249,PMC3376818,22709741,NO-CC CODE,"To compare the timeliness of nongovernmental and governmental communications of infectious disease outbreaks and evaluate trends for each over time, we investigated the time elapsed from the beginning of an outbreak to public reporting of the event. We found that governmental sources improved the timeliness of public reporting of infectious disease outbreaks during the study period.",2012 Jul,"['Mondor, Luke', 'Brownstein, John S.', 'Chan, Emily', 'Madoff, Lawrence C.', 'Pollack, Marjorie P.', 'Buckeridge, David L.', 'Brewer, Timothy F.']",Emerg Infect Dis,,,True
9d867a0457787225540f0aae55979bea536fb74f,PMC,"Calicivirus from Novel Recovirus Genogroup in Human Diarrhea, Bangladesh",http://dx.doi.org/10.3201/eid1807.120344,PMC3376821,22709854,NO-CC CODE,"To identify unknown human viruses in the enteric tract, we examined 105 stool specimens from patients with diarrhea in Bangladesh. A novel calicivirus was identified in a sample from 1 patient and subsequently found in samples from 5 other patients. Phylogenetic analyses classified this virus within the proposed genus Recovirus.",2012 Jul,"['Smits, Saskia L.', 'Rahman, Mustafizur', 'Schapendonk, Claudia M.E.', 'van Leeuwen, Marije', 'Faruque, Abu S.G.', 'Haagmans, Bart L.', 'Endtz, Hubert P.', 'Osterhaus, Albert D.M.E.']",Emerg Infect Dis,,,True
0b78510b912ca51403b0d3d38441d939cb0b5103,PMC,"Calicivirus from Novel Recovirus Genogroup in Human Diarrhea, Bangladesh",http://dx.doi.org/10.3201/eid1807.120344,PMC3376821,22709854,NO-CC CODE,"To identify unknown human viruses in the enteric tract, we examined 105 stool specimens from patients with diarrhea in Bangladesh. A novel calicivirus was identified in a sample from 1 patient and subsequently found in samples from 5 other patients. Phylogenetic analyses classified this virus within the proposed genus Recovirus.",2012 Jul,"['Smits, Saskia L.', 'Rahman, Mustafizur', 'Schapendonk, Claudia M.E.', 'van Leeuwen, Marije', 'Faruque, Abu S.G.', 'Haagmans, Bart L.', 'Endtz, Hubert P.', 'Osterhaus, Albert D.M.E.']",Emerg Infect Dis,,,False
40416d6c18e932e8c5d553c696e9a45c89f4f269,PMC,International Health Regulations—What Gets Measured Gets Done,http://dx.doi.org/10.3201/eid1807.120487,PMC3376826,22709593,NO-CC CODE,"The global spread of severe acute respiratory syndrome highlighted the need to detect and control disease outbreaks at their source, as envisioned by the 2005 revised International Health Regulations (IHR). June 2012 marked the initial deadline by which all 194 World Health Organization (WHO) member states agreed to have IHR core capacities fully implemented for limiting the spread of public health emergencies of international concern. Many countries fell short of these implementation goals and requested a 2-year extension. The degree to which achieving IHR compliance will result in global health security is not clear, but what is clear is that progress against the threat of epidemic disease requires a focused approach that can be monitored and measured efficiently. We developed concrete goals and metrics for 4 of the 8 core capacities with other US government partners in consultation with WHO and national collaborators worldwide. The intent is to offer an example of an approach to implementing and monitoring IHR for consideration or adaptation by countries that complements other frameworks and goals of IHR. Without concrete metrics, IHR may waste its considerable promise as an instrument for global health security against public health emergencies.",2012 Jul,"['Ijaz, Kashef', 'Kasowski, Eric', 'Arthur, Ray R.', 'Angulo, Frederick J.', 'Dowell, Scott F.']",Emerg Infect Dis,,,True
f0cd69cc5ce78e991615973043a3db23a29bab4a,PMC,"Orthopoxvirus DNA in Eurasian Lynx, Sweden",http://dx.doi.org/10.3201/eid1704.091899,PMC3377389,21470451,NO-CC CODE,"Cowpox virus, which has been used to protect humans against smallpox but may cause severe disease in immunocompromised persons, has reemerged in humans, domestic cats, and other animal species in Europe. Orthopoxvirus (OPV) DNA was detected in tissues (lung, kidney, spleen) in 24 (9%) of 263 free-ranging Eurasian lynx (Lynx lynx) from Sweden. Thymidine kinase gene amplicon sequences (339 bp) from 21 lynx were all identical to those from cowpox virus isolated from a person in Norway and phylogenetically closer to monkeypox virus than to vaccinia virus and isolates from 2 persons with cowpox virus in Sweden. Prevalence was higher among animals from regions with dense, rather than rural, human populations. Lynx are probably exposed to OPV through predation on small mammal reservoir species. We conclude that OPV is widely distributed in Sweden and may represent a threat to humans. Further studies are needed to verify whether this lynx OPV is cowpox virus.",2011 Apr,"['Tryland, Morten', 'Okeke, Malachy Ifeanyi', 'af Segerstad, Carl Hård', 'Mörner, Torsten', 'Traavik, Terje', 'Ryser-Degiorgis, Marie-Pierre']",Emerg Infect Dis,,,True
ba59b6a25e1ed76527b1876c403372afda76f4d1,PMC,"Effects of Hand Hygiene Campaigns on Incidence of Laboratory-confirmed Influenza and Absenteeism in Schoolchildren, Cairo, Egypt",http://dx.doi.org/10.3201/eid1704.101353,PMC3377412,21470450,NO-CC CODE,"To evaluate the effectiveness of an intensive hand hygiene campaign on reducing absenteeism caused by influenza-like illness (ILI), diarrhea, conjunctivitis, and laboratory-confirmed influenza, we conducted a randomized control trial in 60 elementary schools in Cairo, Egypt. Children in the intervention schools were required to wash hands twice each day, and health messages were provided through entertainment activities. Data were collected on student absenteeism and reasons for illness. School nurses collected nasal swabs from students with ILI, which were tested by using a qualitative diagnostic test for influenza A and B. Compared with results for the control group, in the intervention group, overall absences caused by ILI, diarrhea, conjunctivitis, and laboratory-confirmed influenza were reduced by 40%, 30%, 67%, and 50%, respectively (p<0.0001 for each illness). An intensive hand hygiene campaign was effective in reducing absenteeism caused by these illnesses.",2011 Apr,"['Talaat, Maha', 'Afifi, Salma', 'Dueger, Erica', 'El-Ashry, Nagwa', 'Marfin, Anthony', 'Kandeel, Amr', 'Mohareb, Emad', 'El-Sayed, Nasr']",Emerg Infect Dis,,,True
f3d353eb411034e59f379d03308d6afcfb7d6da1,PMC,Remaining Questions about Clinical Variola Major,http://dx.doi.org/10.3201/eid1704.101960,PMC3377426,21470458,NO-CC CODE,"After the recent summary of World Health Organization–authorized research on smallpox, several clinical issues remain. This policy review addresses whether early hemorrhagic smallpox is disseminated intravascular coagulation and speculates about the cause of the high mortality rate among pregnant women and whether ocular smallpox is partly the result of trachoma or vitamin A deficiency. The joint destruction common in children with smallpox might be prevented by antiviral drugs, but intraarticular infusion of antiviral drugs is unprecedented. Development of highly effective antiviral drugs against smallpox raises the issue of whether postexposure vaccination can be performed without interference by an antiviral drug. Clinicians should consider whether patients with smallpox should be admitted to general hospitals. Although an adequate supply of second-generation smallpox vaccine exists in the United States, its use is unclear. Finally, political and ethical forces suggest that destruction of the remaining stocks of live smallpox virus is now appropriate.",2011 Apr,"Lane, J. Michael",Emerg Infect Dis,,,True
eac2d30bfd0231911f3879b0d57be63297e4f351,PMC,Sequence Analysis of Feline Coronaviruses and the Circulating Virulent/Avirulent Theory,http://dx.doi.org/10.3201/eid1704.102027,PMC3377428,21470478,NO-CC CODE,,2011 Apr,"['Chang, Hui-Wen', 'Egberink, Herman F.', 'Rottier, Peter J.M.']",Emerg Infect Dis,,,True
38323c6d7602627e8979b5a4a6939f8991a68bf1,PMC,“Filoviruses”: a real pandemic threat?,http://dx.doi.org/10.1002/emmm.200900005,PMC3378103,20049699,NO-CC CODE,"Filoviruses are zoonotic and among the deadliest viruses known to mankind, with mortality rates in outbreaks reaching up to 90%. Despite numerous efforts to identify the host reservoir(s), the transmission cycle of filoviruses between the animal host(s) and humans remains unclear. The last decade has witnessed an increase in filovirus outbreaks with a changing epidemiology. The high mortality rates and lack of effective antiviral drugs or preventive vaccines has propagated the fear that filoviruses may become a real pandemic threat. This article discusses the factors that could influence the possible pandemic potential of filoviruses and elaborates on the prerequisites for the containment of future outbreaks, which would help prevent the evolution of filovirus into more virulent and more transmissible viruses.",2009 Apr,"['Martina, Byron EE', 'Osterhaus, Albert DME']",EMBO Mol Med,,,True
7e3344bab4007d0b919ca28f879e1b6452178041,PMC,Microbiological study of patients hospitalized for acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) and the usefulness of analytical and clinical parameters in its identification (VIRAE study),http://dx.doi.org/10.2147/COPD.S30568,PMC3379868,22745532,NO-CC CODE,"PURPOSE: Respiratory infection is the most common cause for acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). The aim of this work was to study the etiology of the respiratory infection in order to assess the usefulness of the clinical and analytical parameters used for COPD identification. PATIENTS AND METHODS: We included 132 patients over a period of 2 years. The etiology of the respiratory infection was studied by conventional sputum, paired serology tests for atypical bacteria, and viral diagnostic techniques (immunochromatography, immunofluorescence, cell culture, and molecular biology techniques). We grouped the patients into four groups based on the pathogens isolated (bacterial versus. viral, known etiology versus unknown etiology) and compared the groups. RESULTS: A pathogen was identified in 48 patients. The pathogen was identified through sputum culture in 34 patients, seroconversion in three patients, and a positive result from viral techniques in 14 patients. No significant differences in identifying etiology were observed in the clinical and analytical parameters within the different groups. The most cost-effective tests were the sputum test and the polymerase chain reaction. CONCLUSION: Based on our experience, clinical and analytical parameters are not useful for the etiological identification of COPD exacerbations. Diagnosing COPD exacerbation is difficult, with the conventional sputum test for bacterial etiology and molecular biology techniques for viral etiology providing the most profitability. Further studies are necessary to identify respiratory syndromes or analytical parameters that can be used to identify the etiology of new AE-COPD cases without the laborious diagnostic techniques.",2012 May 25,"['Boixeda, Ramon', 'Rabella, Nuria', 'Sauca, Goretti', 'Delgado, Maria', 'Martínez-Costa, Xavier', 'Mauri, Montserrat', 'Vicente, Vanessa', 'Palomera, Elisabet', 'Serra-Prat, Mateu', 'Capdevila, Josep Antón']",Int J Chron Obstruct Pulmon Dis,,,True
191ff4c78c5ff376029d94493b54410fb6662ea6,PMC,"Transmission of Influenza on International Flights, May 2009",http://dx.doi.org/10.3201/eid1707.101135,PMC3381396,21762571,NO-CC CODE,"Understanding the dynamics of influenza transmission on international flights is necessary for prioritizing public health response to pandemic incursions. A retrospective cohort study to ascertain in-flight transmission of pandemic (H1N1) 2009 and influenza-like illness (ILI) was undertaken for 2 long-haul flights entering Australia during May 2009. Combined results, including survey responses from 319 (43%) of 738 passengers, showed that 13 (2%) had an ILI in flight and an ILI developed in 32 (5%) passengers during the first week post arrival. Passengers were at 3.6% increased risk of contracting pandemic (H1N1) 2009 if they sat in the same row as or within 2 rows of persons who were symptomatic preflight. A closer exposed zone (2 seats in front, 2 seats behind, and 2 seats either side) increased the risk for postflight disease to 7.7%. Efficiency of contact tracing without compromising the effectiveness of the public health intervention might be improved by limiting the exposed zone.",2011 Jul,"['Foxwell, A. Ruth', 'Roberts, Leslee', 'Lokuge, Kamalini', 'Kelly, Paul M.']",Emerg Infect Dis,,,True
615f822ea45e03824b752aabd831e2f594608d4a,PMC,"Enteric Coronavirus in Ferrets, the Netherlands",http://dx.doi.org/10.3201/eid1708.110115,PMC3381543,21801658,NO-CC CODE,,2011 Aug,"['Provacia, Lisette B.V.', 'Smits, Saskia L.', 'Martina, Byron E.', 'Raj, V. Stalin', 'v.d. Doel, Petra', 'v. Amerongen, Geert', 'Moorman-Roest, Hanneke', 'Osterhaus, Albert D.M.E.', 'Haagmans, Bart L.']",Emerg Infect Dis,,,True
af6f36f6996b3cbbe64dc659b12f5b2ea5d41fb1,PMC,"Atypical Pestivirus and Severe Respiratory Disease in Calves, Europe",http://dx.doi.org/10.3201/eid1708.101447,PMC3381567,21801648,NO-CC CODE,"In 2010, a HoBi-like pestivirus was isolated from clinically affected calves in Italy. This European virus reproduced a milder form of disease under experimental conditions and was genetically related to previously reported HoBi-like strains. Isolation of this novel virus from a clinical outbreak may have implications for cattle health and prophylactic programs.",2011 Aug,"['Decaro, Nicola', 'Lucente, Maria Stella', 'Mari, Viviana', 'Cirone, Francesco', 'Cordioli, Paolo', 'Camero, Michele', 'Sciarretta, Rossana', 'Losurdo, Michele', 'Lorusso, Eleonora', 'Buonavoglia, Canio']",Emerg Infect Dis,,,True
038f7612653a0732ece011b4cc49e29d305d345b,PMC,Human Bocavirus DNA in Paranasal Sinus Mucosa,http://dx.doi.org/10.3201/eid1708.101944,PMC3381581,21801654,NO-CC CODE,,2011 Aug,"['Falcone, Valeria', 'Ridder, Gerd J.', 'Panning, Marcus', 'Bierbaum, Sibylle', 'Neumann-Haefelin, Dieter', 'Huzly, Daniela']",Emerg Infect Dis,,,True
cc343d904a45985b94b97900c462674c4c8ed237,PMC,"West Nile Virus Infection in Killer Whale, Texas, USA, 2007",http://dx.doi.org/10.3201/eid1708.101979,PMC3381582,21801643,NO-CC CODE,"In 2007, nonsuppurative encephalitis was identified in a killer whale at a Texas, USA, marine park. Panviral DNA microarray of brain tissue suggested West Nile virus (WNV); WNV was confirmed by reverse transcription PCR and sequencing. Immunohistochemistry demonstrated WNV antigen within neurons. WNV should be considered in cases of encephalitis in cetaceans.",2011 Aug,"['St. Leger, Judy', 'Wu, Guang', 'Anderson, Mark', 'Dalton, Les', 'Nilson, Erika', 'Wang, David']",Emerg Infect Dis,,,True
212caadd66e6c2c7c4af2b8fb0c48cfe1ebeb17d,PMC,"Novel Lyssavirus in Natterer’s Bat, Germany",http://dx.doi.org/10.3201/eid1708.110201,PMC3381583,21801640,NO-CC CODE,"A virus isolated from a Natterer’s bat (Myotis nattererii) in Germany was differentiated from other lyssaviruses on the basis of the reaction pattern of a panel of monoclonal antibodies. Phylogenetic analysis supported the assumption that the isolated virus, Bokeloh bat lyssavirus, may represent a new member of the genus Lyssavirus.",2011 Aug,"['Freuling, Conrad M.', 'Beer, Martin', 'Conraths, Franz J.', 'Finke, Stefan', 'Hoffmann, Bernd', 'Keller, Barbara', 'Kliemt, Jeannette', 'Mettenleiter, Thomas C.', 'Mühlbach, Elke', 'Teifke, Jens P.', 'Wohlsein, Peter', 'Müller, Thomas']",Emerg Infect Dis,,,True
85fadc26663d1add5c2e6effd39b37d8720528fc,PMC,Novel Human Reovirus Isolated from Children with Acute Necrotizing Encephalopathy,http://dx.doi.org/10.3201/eid1708.101528,PMC3381585,21801621,NO-CC CODE,"For many encephalitis cases, the cause remains unidentified. After 2 children (from the same family) received a diagnosis of acute necrotizing encephalopathy at Centre Hospitalier Universitaire (Tours, France), we attempted to identify the etiologic agent. Because clinical samples from the 2 patients were negative for all pathogens tested, urine and throat swab specimens were added to epithelial cells, and virus isolates detected were characterized by molecular analysis and electron microscopy. We identified a novel reovirus strain (serotype 2), MRV2Tou05, which seems to be closely related to porcine and human strains. A specific antibody response directed against this new reovirus strain was observed in convalescent-phase serum specimens from the patients, whereas no response was observed in 38 serum specimens from 38 healthy adults. This novel reovirus is a new etiologic agent of encephalitis.",2011 Aug,"['Ouattara, Louise A.', 'Barin, Francis', 'Barthez, Marie Anne', 'Bonnaud, Bertrand', 'Roingeard, Philippe', 'Goudeau, Alain', 'Castelnau, Pierre', 'Vernet, Guy', 'Paranhos-Baccalà, Gláucia', 'Komurian-Pradel, Florence']",Emerg Infect Dis,,,True
9b5ccd6bdaec71cd24d8c9122c6a6b868bdd22a0,PMC,"Outbreak of Porcine Epidemic Diarrhea in Suckling Piglets, China",http://dx.doi.org/10.3201/eid1801.111259,PMC3381683,22261231,NO-CC CODE,,2012 Jan,"['Sun, Rui-Qin', 'Cai, Ru-Jian', 'Chen, Ya-Qiang', 'Liang, Peng-Shuai', 'Chen, De-Kun', 'Song, Chang-Xu']",Emerg Infect Dis,,,True
0498793e595e90458c63f2f26b7bee68050cfdbc,PMC,"Outbreak of Porcine Epidemic Diarrhea in Suckling Piglets, China",http://dx.doi.org/10.3201/eid1801.111259,PMC3381683,22261231,NO-CC CODE,,2012 Jan,"['Sun, Rui-Qin', 'Cai, Ru-Jian', 'Chen, Ya-Qiang', 'Liang, Peng-Shuai', 'Chen, De-Kun', 'Song, Chang-Xu']",Emerg Infect Dis,,,False
0aa9c6e5d23acccfae9077750071e2768bdeefe6,PMC,Yeast and the AIDS Virus: The Odd Couple,http://dx.doi.org/10.1155/2012/549020,PMC3385842,22778552,NO-CC CODE,"Despite being simple eukaryotic organisms, the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe have been widely used as a model to study human pathologies and the replication of human, animal, and plant viruses, as well as the function of individual viral proteins. The complete genome of S. cerevisiae was the first of eukaryotic origin to be sequenced and contains about 6,000 genes. More than 75% of the genes have an assigned function, while more than 40% share conserved sequences with known or predicted human genes. This strong homology has allowed the function of human orthologs to be unveiled starting from the data obtained in yeast. RNA plant viruses were the first to be studied in yeast. In this paper, we focus on the use of the yeast model to study the function of the proteins of human immunodeficiency virus type 1 (HIV-1) and the search for its cellular partners. This human retrovirus is the cause of AIDS. The WHO estimates that there are 33.4 million people worldwide living with HIV/AIDS, with 2.7 million new HIV infections per year and 2.0 million annual deaths due to AIDS. Current therapy is able to control the disease but there is no permanent cure or a vaccine. By using yeast, it is possible to dissect the function of some HIV-1 proteins and discover new cellular factors common to this simple cell and humans that may become potential therapeutic targets, leading to a long-lasting treatment for AIDS.",2012 Jun 17,"['Andréola, Marie-Line', 'Litvak, Simon']",J Biomed Biotechnol,,,True
81496ab8f06bbb9f90b5e7773b8e6c6db6e02b2a,PMC,Peptide-mediated Cell and In Vivo Delivery of Antisense Oligonucleotides and siRNA,http://dx.doi.org/10.1038/mtna.2012.18,PMC3390225,23344079,NO-CC CODE,,2012 Jun 12,"['Järver, Peter', 'Coursindel, Thibault', 'Andaloussi, Samir EL', 'Godfrey, Caroline', 'Wood, Matthew JA', 'Gait, Michael J']",Mol Ther Nucleic Acids,,,True
be602928156cf0ace9899c1c8569eb4f4ea4597b,PMC,Pro/Con debate: Are barrier precautions cost-effective in improving patient outcomes in the intensive care unit?,http://dx.doi.org/10.1186/cc10532,PMC3396214,22264293,NO-CC CODE,"You are responsible for a large medical surgical ICU. Your hospital administration has been very focused on reducing rates of hospital-acquired infections particularly in the wake of increasing public attention. However, it is time for budget preparation and your financial officer is concerned about the escalating costs associated with patient isolation and barrier precautions/personal protective equipment. Having become aware of the high costs associated with these interventions, you start to wonder about the wisdom of spending so much in this area. Your hospital administration wants your direction on next year's expenditures. You are debating whether the expense is worthwhile and advise your hospital administration accordingly.",2012 Jan 19,"['Thampi, Nisha', 'Morris, Andrew M']",Crit Care,,,True
85ea36d6f12f1998c292532c97cc228ee305271f,PMC,Preparation of an antitumor and antivirus agent: chemical modification of α-MMC and MAP30 from Momordica Charantia L. with covalent conjugation of polyethyelene glycol,http://dx.doi.org/10.2147/IJN.S30631,PMC3396394,22802682,NO-CC CODE,"BACKGROUND: Alpha-momorcharin (α-MMC) and momordica anti-HIV protein (MAP30) derived from Momordica charantia L. have been confirmed to possess antitumor and antivirus activities due to their RNA-N-glycosidase activity. However, strong immunogenicity and short plasma half-life limit their clinical application. To solve this problem, the two proteins were modified with (mPEG)(2)-Lys-NHS (20 kDa). METHODOLOGY/PRINCIPAL FINDINGS: In this article, a novel purification strategy for the two main type I ribosome-inactivating proteins (RIPs), α-MMC and MAP30, was successfully developed for laboratory-scale preparation. Using this dramatic method, 200 mg of α-MMC and about 120 mg of MAP30 was obtained in only one purification process from 200 g of Momordica charantia seeds. The homogeneity and some other properties of the two proteins were assessed by gradient SDS-PAGE, electrospray ionization quadruple mass spectrometry, and N-terminal sequence analysis as well as Western blot. Two polyethylene glycol (PEG)ylated proteins were synthesized and purified. Homogeneous mono-, di-, or tri-PEGylated proteins were characterized by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The analysis of antitumor and antivirus activities indicated that the serial PEGylated RIPs preserved moderate activities on JAR choriocarcinoma cells and herpes simplex virus-1. Furthermore, both PEGylated proteins showed about 60%–70% antitumor and antivirus activities, and at the same time decreased 50%–70% immunogenicity when compared with their unmodified counterparts. CONCLUSION/SIGNIFICANCE: α-MMC and MAP30 obtained from this novel purification strategy can meet the requirement of a large amount of samples for research. Their chemical modification can solve the problem of strong immunogenicity and meanwhile preserve moderate activities. All these findings suggest the potential application of PEGylated α-MMC and PEGylated MAP30 as antitumor and antivirus agents. According to these results, PEGylated RIPs can be constructed with nanomaterials to be a targeting drug that can further decrease immunogenicity and side effects. Through nanotechnology we can make them low-release drugs, which can further prolong their half-life period in the human body.",2012 Jun 27,"['Meng, Yao', 'Liu, Shuangfeng', 'Li, Juan', 'Meng, Yanfa', 'Zhao, Xiaojun']",Int J Nanomedicine,,,True
678afd3fc1f3aba4346f2513ce3a4550794d5cad,PMC,Jasmonic Acid (JA) Acts as a Signal Molecule in LaCl(3)-Induced Baicalin Synthesis in Scutellaria baicalensis Seedlings,http://dx.doi.org/10.1007/s12011-012-9379-8,PMC3399072,22476950,NO-CC CODE,"Rare earth elements (REEs) have been widely used to increase accumulation of biomass and secondary metabolites in medicinal plants in China. However, very few studies have investigated how REEs mediate secondary metabolism synthesis in medicinal plants. Lanthanum (La), an important REE, is known to improve the accumulation of secondary metabolites in medicinal plants and is widely distributed in China. However, few studies have evaluated the signal transduction leading to La-induced secondary metabolism in medicinal plants. In this study, LaCl(3) treatment-induced multiple responses in Scutellaria baicalensis seedlings, including the rapid generation of jasmonic acid (JA), sequentially followed by the enhancement of baicalin production. Direct application of JA also promoted the synthesis of baicalin in the absence of LaCl(3). LaCl(3)-induced baicalin synthesis was blocked by two different JA synthesis inhibitors. Our results showed that JA acts as a signal component within the signaling system leading to La-induced baicalin synthesis in S. baicalensis seedlings.",2012 Sep 3,"['Zhou, Jie', 'Fang, Lei', 'Li, Xuan', 'Guo, Lanping', 'Huang, Luqi']",Biol Trace Elem Res,,,True
eba4fe7ae5e8a69de34227a077e2050f4a93cb2f,PMC,Diversity and roles of (t)RNA ligases,http://dx.doi.org/10.1007/s00018-012-0944-2,PMC3400036,22426497,NO-CC CODE,"The discovery of discontiguous tRNA genes triggered studies dissecting the process of tRNA splicing. As a result, we have gained detailed mechanistic knowledge on enzymatic removal of tRNA introns catalyzed by endonuclease and ligase proteins. In addition to the elucidation of tRNA processing, these studies facilitated the discovery of additional functions of RNA ligases such as RNA repair and non-conventional mRNA splicing events. Recently, the identification of a new type of RNA ligases in bacteria, archaea, and humans closed a long-standing gap in the field of tRNA processing. This review summarizes past and recent findings in the field of tRNA splicing with a focus on RNA ligation as it preferentially occurs in archaea and humans. In addition to providing an integrated view of the types and phyletic distribution of RNA ligase proteins known to date, this survey also aims at highlighting known and potential accessory biological functions of RNA ligases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00018-012-0944-2) contains supplementary material, which is available to authorized users.",2012 Aug 17,"['Popow, Johannes', 'Schleiffer, Alexander', 'Martinez, Javier']",Cell Mol Life Sci,,,True
d6a5a00ad9468ae27a3a1c7cc33c2131297fbaa9,PMC,Engineered hepatitis B virus surface antigen L protein particles for in vivo active targeting of splenic dendritic cells,http://dx.doi.org/10.2147/IJN.S32813,PMC3405891,22848163,NO-CC CODE,"Dendritic cells (DCs) are key regulators of adaptive T-cell responses. By capturing exogenous antigens and presenting antigen-derived peptides via major histocompatibility complex molecules to naïve T cells, DCs induce antigen-specific immune responses in vivo. In order to induce effective host immune responses, active delivery of exogenous antigens to DCs is considered important for future vaccine development. We recently generated bionanocapsules (BNCs) consisting of hepatitis B virus surface antigens that mediate stringent in vivo cell targeting and efficient endosomal escape, and after the fusion with liposomes (LP) containing therapeutic materials, the BNC-LP complexes deliver them to human liver-derived tissues in vivo. BNCs were further modified to present the immunoglobulin G (IgG) Fc-interacting domain (Z domain) derived from Staphylococcus aureus protein A in tandem. When mixed with IgGs, modified BNCs (ZZ-BNCs) displayed the IgG Fv regions outwardly for efficient binding to antigens in an oriented-immobilization manner. Due to the affinity of the displayed IgGs, the IgG-ZZ-BNC complexes accumulated in specific cells and tissues in vitro and in vivo. After mixing ZZ-BNCs with antibodies against DCs, we used immunocytochemistry to examine which antibodies delivered ZZ-BNCs to mouse splenic DCs following intravenous injection of the ZZ-BNCs. ZZ-BNCs displaying anti-CD11c monoclonal antibodies (α-CD11c-ZZ-BNCs) were found to accumulate with approximately 62% of splenic DCs, and reside within some of them. After the fusion with liposomes containing antigens, the α-CD11c-ZZ-BNCs could elicit the respective antibodies more efficiently than other nontargeting control vaccines, suggesting that this DC-specific nanocarrier is promising for future vaccines.",2012 Jul 3,"['Matsuo, Hidenori', 'Yoshimoto, Nobuo', 'Iijima, Masumi', 'Niimi, Tomoaki', 'Jung, Joohee', 'Jeong, Seong-Yun', 'Choi, Eun Kyung', 'Sewaki, Tomomitsu', 'Arakawa, Takeshi', 'Kuroda, Shun’ichi']",Int J Nanomedicine,,,True
843f0cacbbf8ea36f7638c26564c118035284f40,PMC,Structural Basis of Evasion of Cellular Adaptive Immunity by HIV-1 Nef,http://dx.doi.org/10.1038/nsmb.2328,PMC3407041,22705789,NO-CC CODE,"The HIV-1 protein Nef inhibits antigen presentation by class I MHC (MHC-I). Here the mechanism of this activity is revealed by the crystal structure of a protein complex consisting of Nef, the MHC-I cytoplasmic domain (MHC-I CD), and the μ1 subunit of the clathrin adaptor protein complex 1. A ternary, cooperative interaction clamps the MHC-I CD into a narrow binding groove at the Nef-μ1 interface encompassing the cargo-recognition site of μ1 and the proline rich strand of Nef. The Nef C-terminus induces a novel conformational change in μ1, while the N-terminus binds the Nef core to position it optimally for complex formation. Positively charged patches on μ1 recognize acidic clusters in Nef and MHC-I. The structure shows how Nef functions as a clathrin-associated sorting protein to alter the specificity of host membrane trafficking and enable viral evasion of adaptive immunity.",2012 Jun 17,"['Jia, Xiaofei', 'Singh, Rajendra', 'Homann, Stefanie', 'Yang, Haitao', 'Guatelli, John', 'Xiong, Yong']",Nat Struct Mol Biol,,,True
9b4046783634f1eaca7edb9524cd9930f4cc8b99,PMC,Structural Basis of Evasion of Cellular Adaptive Immunity by HIV-1 Nef,http://dx.doi.org/10.1038/nsmb.2328,PMC3407041,22705789,NO-CC CODE,"The HIV-1 protein Nef inhibits antigen presentation by class I MHC (MHC-I). Here the mechanism of this activity is revealed by the crystal structure of a protein complex consisting of Nef, the MHC-I cytoplasmic domain (MHC-I CD), and the μ1 subunit of the clathrin adaptor protein complex 1. A ternary, cooperative interaction clamps the MHC-I CD into a narrow binding groove at the Nef-μ1 interface encompassing the cargo-recognition site of μ1 and the proline rich strand of Nef. The Nef C-terminus induces a novel conformational change in μ1, while the N-terminus binds the Nef core to position it optimally for complex formation. Positively charged patches on μ1 recognize acidic clusters in Nef and MHC-I. The structure shows how Nef functions as a clathrin-associated sorting protein to alter the specificity of host membrane trafficking and enable viral evasion of adaptive immunity.",2012 Jun 17,"['Jia, Xiaofei', 'Singh, Rajendra', 'Homann, Stefanie', 'Yang, Haitao', 'Guatelli, John', 'Xiong, Yong']",Nat Struct Mol Biol,,,False
fd82025c545a45eb4e5701d19effecf2388f613a,PMC,Mesoniviridae: a proposed new family in the order Nidovirales formed by a single species of mosquito-borne viruses,http://dx.doi.org/10.1007/s00705-012-1295-x,PMC3407358,22527862,NO-CC CODE,"Recently, two independent surveillance studies in Côte d’Ivoire and Vietnam, respectively, led to the discovery of two mosquito-borne viruses, Cavally virus and Nam Dinh virus, with genome and proteome properties typical for viruses of the order Nidovirales. Using a state-of-the-art approach, we show that the two insect nidoviruses are (i) sufficiently different from other nidoviruses to represent a new virus family, and (ii) related to each other closely enough to be placed in the same virus species. We propose to name this new family Mesoniviridae. Meso is derived from the Greek word “mesos” (in English “in the middle”) and refers to the distinctive genome size of these insect nidoviruses, which is intermediate between that of the families Arteriviridae and Coronaviridae, while ni is an abbreviation for “nido”. A taxonomic proposal to establish the new family Mesoniviridae, genus Alphamesonivirus, and species Alphamesonivirus 1 has been approved for consideration by the Executive Committee of the ICTV.",2012 Aug 24,"['Lauber, Chris', 'Ziebuhr, John', 'Junglen, Sandra', 'Drosten, Christian', 'Zirkel, Florian', 'Nga, Phan Thi', 'Morita, Kouichi', 'Snijder, Eric J.', 'Gorbalenya, Alexander E.']",Arch Virol,,,True
7bf0ed5268fb6a4f25291a4a0841b50791be018b,PMC,"Novel Hepatitis E Virus in Ferrets, the Netherlands",http://dx.doi.org/10.3201/eid1808.111659,PMC3414025,22840220,NO-CC CODE,,2012 Aug,"['Raj, V. Stalin', 'Smits, Saskia L.', 'Pas, Suzan D.', 'Provacia, Lisette B.V.', 'Moorman-Roest, Hanneke', 'Osterhaus, Albert D.M.E.', 'Haagmans, Bart L.']",Emerg Infect Dis,,,True
f9a38a8e26ffe3c3a028f67a4ffc622a7d63661e,PMC,"Novel Hepatitis E Virus in Ferrets, the Netherlands",http://dx.doi.org/10.3201/eid1808.111659,PMC3414025,22840220,NO-CC CODE,,2012 Aug,"['Raj, V. Stalin', 'Smits, Saskia L.', 'Pas, Suzan D.', 'Provacia, Lisette B.V.', 'Moorman-Roest, Hanneke', 'Osterhaus, Albert D.M.E.', 'Haagmans, Bart L.']",Emerg Infect Dis,,,False
144a42d199c75de765dbf0d0ec7b32a0f9b30dc4,PMC,"New Variants of Porcine Epidemic Diarrhea Virus, China, 2011",http://dx.doi.org/10.3201/eid1808.120002,PMC3414035,22840964,NO-CC CODE,"In 2011, porcine epidemic diarrhea virus (PEDV) infection rates rose substantially in vaccinated swine herds. To determine the distribution profile of PEDV outbreak strains, we sequenced the full-length spike gene from samples from 9 farms where animals exhibited severe diarrhea and mortality rates were high. Three new PEDV variants were identified.",2012 Aug,"['Li, Wentao', 'Li, Heng', 'Liu, Yunbo', 'Pan, Yongfei', 'Deng, Feng', 'Song, Yanhua', 'Tang, Xibiao', 'He, Qigai']",Emerg Infect Dis,,,True
798e12b3a2ba2e004b662673aa590e8d7fe6f3b9,PMC,"New Variants of Porcine Epidemic Diarrhea Virus, China, 2011",http://dx.doi.org/10.3201/eid1808.120002,PMC3414035,22840964,NO-CC CODE,"In 2011, porcine epidemic diarrhea virus (PEDV) infection rates rose substantially in vaccinated swine herds. To determine the distribution profile of PEDV outbreak strains, we sequenced the full-length spike gene from samples from 9 farms where animals exhibited severe diarrhea and mortality rates were high. Three new PEDV variants were identified.",2012 Aug,"['Li, Wentao', 'Li, Heng', 'Liu, Yunbo', 'Pan, Yongfei', 'Deng, Feng', 'Song, Yanhua', 'Tang, Xibiao', 'He, Qigai']",Emerg Infect Dis,,,False
06559dd625491d6474ee88f08c12fc17c1830995,PMC,"Towards evidence-based, GIS-driven national spatial health information infrastructure and surveillance services in the United Kingdom",http://dx.doi.org/10.1186/1476-072X-3-1,PMC343292,14748927,NO-CC CODE,"The term ""Geographic Information Systems"" (GIS) has been added to MeSH in 2003, a step reflecting the importance and growing use of GIS in health and healthcare research and practices. GIS have much more to offer than the obvious digital cartography (map) functions. From a community health perspective, GIS could potentially act as powerful evidence-based practice tools for early problem detection and solving. When properly used, GIS can: inform and educate (professionals and the public); empower decision-making at all levels; help in planning and tweaking clinically and cost-effective actions, in predicting outcomes before making any financial commitments and ascribing priorities in a climate of finite resources; change practices; and continually monitor and analyse changes, as well as sentinel events. Yet despite all these potentials for GIS, they remain under-utilised in the UK National Health Service (NHS). This paper has the following objectives: (1) to illustrate with practical, real-world scenarios and examples from the literature the different GIS methods and uses to improve community health and healthcare practices, e.g., for improving hospital bed availability, in community health and bioterrorism surveillance services, and in the latest SARS outbreak; (2) to discuss challenges and problems currently hindering the wide-scale adoption of GIS across the NHS; and (3) to identify the most important requirements and ingredients for addressing these challenges, and realising GIS potential within the NHS, guided by related initiatives worldwide. The ultimate goal is to illuminate the road towards implementing a comprehensive national, multi-agency spatio-temporal health information infrastructure functioning proactively in real time. The concepts and principles presented in this paper can be also applied in other countries, and on regional (e.g., European Union) and global levels.",2004 Jan 28,"Boulos, Maged N Kamel",Int J Health Geogr,,,True
d81ae79ebc6462fd3de075e220992f1aae1f06ae,PMC,Descriptive review of geographic mapping of severe acute respiratory syndrome (SARS) on the Internet,http://dx.doi.org/10.1186/1476-072X-3-2,PMC343293,14748926,NO-CC CODE,"From geographic mapping at different scales to location-based alerting services, geoinformatics plays an important role in the study and control of global outbreaks like severe acute respiratory syndrome (SARS). This paper reviews several geographic mapping efforts of SARS on the Internet that employ a variety of techniques like choropleth rendering, graduated circles, graduated pie charts, buffering, overlay analysis and animation. The aim of these mapping services is to educate the public (especially travellers to potentially at-risk areas) and assist public health authorities in analysing the spatial and temporal trends and patterns of SARS and in assessing/revising current control measures.",2004 Jan 28,"Boulos, Maged N Kamel",Int J Health Geogr,,,True
e1dd5b5b1884508b0e49421388eb658f9f9949e1,PMC,Environmental and non-infectious factors in the aetiology of pharyngitis (sore throat),http://dx.doi.org/10.1007/s00011-012-0540-9,PMC3439613,22890476,NO-CC CODE,"OBJECTIVES: The aim of this review is to examine the causes, pathophysiology and experimental models of non-infectious pharyngitis (sore throat). INTRODUCTION: The causes of sore throat can be infectious (viruses, bacteria, and fungi) or non-infectious, although the relative proportion of each is not well documented. METHODS: A PubMed database search was performed for studies of non-infectious sore throat. RESULTS AND CONCLUSIONS: Non-infectious causes of sore throat include: physico-chemical factors, such as smoking, snoring, shouting, tracheal intubation, medications, or concomitant illness; and environmental factors including indoor and outdoor air pollutants, temperature and humidity, and hazardous or occupational irritants. The pathophysiology underlying non-infectious sore throat is largely uncharacterised, although neurogenic inflammation looks to be a promising candidate. It is likely that there will be individual disposition factors or the coincidence of more than one irritant with possible—up to now unknown—interactions between them. Therefore, experimental models with defined conditions and objective endpoints are needed. A new model using cold dry air to directly induce pharyngeal irritation in humans, with pharyngeal lavage to measure biomarkers, may provide a useful tool for the study of mechanisms and treatment of non-infectious sore throat.",2012 Oct 14,"['Renner, Bertold', 'Mueller, Christian A.', 'Shephard, Adrian']",Inflamm Res,,,True
98fd9db3d54a142771aa760cdfcbd53b7cfbd0ed,PMC,Challenge models to assess new therapies in chronic obstructive pulmonary disease,http://dx.doi.org/10.2147/COPD.S30664,PMC3459659,23055710,NO-CC CODE,"Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Current therapies confer partial benefits either by incompletely improving airflow limitation or by reducing acute exacerbations, hence new therapies are desirable. In the absence of robust early predictors of clinical efficacy, the potential success of novel therapeutic agents in COPD will not entirely be known until the drugs enter relatively large and costly clinical trials. New predictive models in humans, and new study designs are being sought to allow for confirmation of pharmacodynamic and potentially clinically meaningful effects in early development. This review focuses on human challenge models with lipopolysaccharide endotoxin, ozone, and rhinovirus, in the early clinical development phases of novel therapeutic agents for the treatment and reduction of exacerbations in COPD.",2012 Sep 13,"['van der Merwe, René', 'Molfino, Nestor A']",Int J Chron Obstruct Pulmon Dis,,,True
9f08226b10da36589025f4b568fa4734be47f0c1,PMC,Influenza Virus Infection in Nonhuman Primates,http://dx.doi.org/10.3201/eid1810.120214,PMC3471624,23017256,NO-CC CODE,"To determine whether nonhuman primates are infected with influenza viruses in nature, we conducted serologic and swab studies among macaques from several parts of the world. Our detection of influenza virus and antibodies to influenza virus raises questions about the role of nonhuman primates in the ecology of influenza.",2012 Oct,"['Karlsson, Erik A.', 'Engel, Gregory A.', 'Feeroz, M.M.', 'San, Sorn', 'Rompis, Aida', 'Lee, Benjamin P. Y.-H.', 'Shaw, Eric', 'Oh, Gunwha', 'Schillaci, Michael A.', 'Grant, Richard', 'Heidrich, John', 'Schultz-Cherry, Stacey', 'Jones-Engel, Lisa']",Emerg Infect Dis,,,True
d8b36980251bf7abdc4d17ff7ef4baf1899f0540,PMC,WU and KI Polyomaviruses in Respiratory Samples from Allogeneic Hematopoietic Cell Transplant Recipients,http://dx.doi.org/10.3201/eid1810.120477,PMC3471632,23017213,NO-CC CODE,"Data are limited regarding 2 new human polyomaviruses, KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV), in immunocompromised patients. We used real-time PCR to test for these and 12 respiratory viruses in 2,732 nasal wash samples collected during the first year after allogeneic hematopoietic cell transplantation from 222 patients. Specimens were collected weekly until day 100; then at least every 3 months. One year after hematopoietic cell transplantation, the cumulative incidence estimate was 26% for KIPyV and 8% for WUPyV. Age <20 years predicted detection of KIPyV (hazard ratio [HR] 4.6) and WUPyV (HR 4.4), and detection of a respiratory virus in the previous 2 weeks predicted KIPyV detection (HR 3.4). Sputum production and wheezing were associated with detection of KIPyV in the past week and WUPyV in the past month. There were no associations with polyomavirus detection and acute graft versus host disease, cytomegalovirus reactivation, neutropenia, lymphopenia, hospitalization, or death.",2012 Oct,"['Kuypers, Jane', 'Campbell, Angela P.', 'Guthrie, Katherine A.', 'Wright, Nancy L.', 'Englund, Janet A.', 'Corey, Lawrence', 'Boeckh, Michael']",Emerg Infect Dis,,,True
fc5396c4fb0587a9741ed6ab1bec5c6cd8da1b17,PMC,ECR 2012 Book of Abstracts - A - Postergraduate Educational Programme,http://dx.doi.org/10.1007/s13244-012-0153-4,PMC3481066,22696127,NO-CC CODE,,2012 Mar 21,,Insights Imaging,,,True
557c406ad2a9c8dec744c69b3e7ac9621e3d6f66,PMC,"History of the World Allergy Organization: Two Decades Leading to World Leadership, 1990–2010",http://dx.doi.org/10.1097/WOX.0b013e31823ba552,PMC3488903,23268440,NO-CC CODE,,2011 Nov 18,"Kaliner, Michael A.",World Allergy Organ J,,,True
5deba58c72c66f2c3f47ec82569c9b2527f6f21d,PMC,"Toxicology, biodistribution and shedding profile of a recombinant measles vaccine vector expressing HIV-1 antigens, in cynomolgus macaques",http://dx.doi.org/10.1007/s00210-012-0793-4,PMC3495096,22983013,NO-CC CODE,"As a new human immunodeficiency virus type 1 (HIV-1) vaccine approach, the live-attenuated measles virus (MV) Schwarz vaccine strain was genetically engineered to express the F4 antigen (MV1-F4). F4 is a fusion protein comprising HIV-1 antigens p17 and p24, reverse transcriptase and Nef. This study assessed the toxicity, biodistribution and shedding profiles of MV1-F4. Cynomolgus macaques were intramuscularly immunized one or three times with the highest dose of MV1-F4 intended for clinical use, the reference (Schwarz) measles vaccine or saline, and monitored clinically for 11 or 85 days. Toxicological parameters included local and systemic clinical signs, organ weights, haematology, clinical and gross pathology and histopathology. Both vaccines were well tolerated, with no morbidity, clinical signs or gross pathological findings observed. Mean spleen weights were increased after three doses of either vaccine, which corresponded with increased numbers and/or sizes of germinal centers. This was likely a result of the immune response to the vaccines. Either vaccine virus replicated preferentially in secondary lymphoid organs and to a lesser extent in epithelium-rich tissues (e.g., intestine, urinary bladder and trachea) and the liver. At the expected peak of viremia, viral RNA was detected in some biological fluid samples from few animals immunized with either vaccine, but none of these samples contained infectious virus. In conclusion, no shedding of infectious viral particles was identified in cynomolgus monkeys after injection of MV1-F4 or Schwarz measles vaccines. Furthermore, no toxic effect in relation to the MV vaccination was found with these vaccines in this study.",2012 Dec 16,"['Lorin, Clarisse', 'Segal, Lawrence', 'Mols, Johann', 'Morelle, Danielle', 'Bourguignon, Patricia', 'Rovira, Olga', 'Mettens, Pascal', 'Silvano, Jérémy', 'Dumey, Nicolas', 'Le Goff, Frédérick', 'Koutsoukos, Marguerite', 'Voss, Gerald', 'Tangy, Frédéric']",Naunyn Schmiedebergs Arch Pharmacol,,,True
3f3401216256123b750a1d70058fea8af14ec311,PMC,"Possibilities, Intentions and Threats: Dual Use in the Life Sciences Reconsidered",http://dx.doi.org/10.1007/s11948-011-9266-2,PMC3513596,21327859,NO-CC CODE,"Due to the terrorist attacks of 9/11 and the anthrax letters of a few weeks later, the concept of dual use has spread widely in the life sciences during the past decade. This article is aimed at a clarification of the dual use concept and its scope of application for the life sciences. Such a clarification would greatly facilitate the work of policymakers seeking to ensure security while avoiding undesirable interventions of government in the conduct of science. The article starts with an overview of the main developments in life sciences in relation to dual use. This is illustrated by discussions on synthetic biology and dual use. The findings lead to a reconsideration of the dual use concept. An area in need of further attention is to what extent threats and intentions should have impact on the definition of dual use. Possible threats are analyzed against the background of the phenomenon of securitization of health care and life sciences: considering these sectors of society in security terms. Some caveats that should be taken into account in a dual use policy are described. An acceptable, adequate and applicable definition of the dual use concept could help researchers, universities, companies and policy makers. Such a definition should build upon, but go beyond, the view developed in the influential Fink-report, which concentrates on the so-called ‘experiments of concern’, e.g. experiments that enhance the virulence of pathogens (National Research Council of the National Academies 2004) It will be argued that—in addition to these more technical aspects—a definition of dual use should include the aspect of threats and intentions.",2012 Dec 17,"van der Bruggen, Koos",Sci Eng Ethics,,,True
ed2de3694f5580ea38f4adf24bd1c8b46862df1f,PMC,Mannose-binding lectin deficiency and acute exacerbations of chronic obstructive pulmonary disease,http://dx.doi.org/10.2147/COPD.S33714,PMC3514010,23226013,NO-CC CODE,"BACKGROUND: Mannose-binding lectin is a collectin involved in host defense against infection. Whether mannose-binding lectin deficiency is associated with acute exacerbations of chronic obstructive pulmonary disease is debated. METHODS: Participants in a study designed to determine if azithromycin taken daily for one year decreased acute exacerbations had serum mannose-binding lectin concentrations measured at the time of enrollment. RESULTS: Samples were obtained from 1037 subjects (91%) in the trial. The prevalence of mannose-binding lectin deficiency ranged from 0.5% to 52.2%, depending on how deficiency was defined. No differences in the prevalence of deficiency were observed with respect to any demographic variable assessed, and no differences were observed in time to first exacerbation, rate of exacerbations, or percentage of subjects requiring hospitalization for exacerbations in those with deficiency versus those without, regardless of how deficiency was defined. CONCLUSION: In a large sample of subjects with chronic obstructive pulmonary disease selected for having an increased risk of experiencing an acute exacerbation of chronic obstructive pulmonary disease, only 1.9% had mannose-binding lectin concentrations below the normal range and we found no association between mannose-binding lectin concentrations and time to first acute exacerbation or frequency of acute exacerbations during one year of prospective follow-up.",2012 Nov 23,"['Albert, Richard K', 'Connett, John', 'Curtis, Jeffrey L', 'Martinez, Fernando J', 'Han, MeiLan K', 'Lazarus, Stephen C', 'Woodruff, Prescott G']",Int J Chron Obstruct Pulmon Dis,,,True
a0d46c310512552aeb8e88f5a5d0c11f42fffcc8,PMC,"A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease",http://dx.doi.org/10.1038/nm.2972,PMC3518599,23142821,NO-CC CODE,"Live-attenuated RNA virus vaccines are efficacious but subject to reversion to virulence. Among RNA viruses, replication fidelity is recognized as a key determinant of virulence and escape from antiviral therapy; increased fidelity is attenuating for some viruses. Coronavirus replication fidelity is approximately 20-fold greater than that of other RNA viruses and is mediated by a 3′-5′ exonuclease activity (ExoN) that likely functions in RNA proofreading. In this study, we demonstrate that engineered inactivation of SARS-CoV ExoN activity results in a stable mutator phenotype with profoundly decreased fidelity in vivo and attenuation of pathogenesis in young, aged, and immunocompromised mouse models of human SARS. The ExoN inactivation genotype and mutator phenotype are stable and do not revert to virulence, even after serial passage or long-term persistent infection in vivo. Our approach represents a strategy with potential for broad applications for the stable attenuation of coronaviruses and possibly other RNA viruses.",2012 Dec 11,"['Graham, Rachel L.', 'Becker, Michelle M.', 'Eckerle, Lance D.', 'Bolles, Meagan', 'Denison, Mark R.', 'Baric, Ralph S.']",Nat Med,,,True
f631c65ac148fd2987bb614f648c90d6225d0d28,PMC,"A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease",http://dx.doi.org/10.1038/nm.2972,PMC3518599,23142821,NO-CC CODE,"Live-attenuated RNA virus vaccines are efficacious but subject to reversion to virulence. Among RNA viruses, replication fidelity is recognized as a key determinant of virulence and escape from antiviral therapy; increased fidelity is attenuating for some viruses. Coronavirus replication fidelity is approximately 20-fold greater than that of other RNA viruses and is mediated by a 3′-5′ exonuclease activity (ExoN) that likely functions in RNA proofreading. In this study, we demonstrate that engineered inactivation of SARS-CoV ExoN activity results in a stable mutator phenotype with profoundly decreased fidelity in vivo and attenuation of pathogenesis in young, aged, and immunocompromised mouse models of human SARS. The ExoN inactivation genotype and mutator phenotype are stable and do not revert to virulence, even after serial passage or long-term persistent infection in vivo. Our approach represents a strategy with potential for broad applications for the stable attenuation of coronaviruses and possibly other RNA viruses.",2012 Dec 11,"['Graham, Rachel L.', 'Becker, Michelle M.', 'Eckerle, Lance D.', 'Bolles, Meagan', 'Denison, Mark R.', 'Baric, Ralph S.']",Nat Med,,,False
35c420fb4598e8d833173d957564539f37162d0d,PMC,Trex1 regulates lysosomal biogenesis and interferon-independent activation of antiviral genes,http://dx.doi.org/10.1038/ni.2475,PMC3522772,23160154,NO-CC CODE,"Innate immune sensing of viral nucleic acids triggers type I interferon (IFN) production, which activates interferon-stimulated genes (ISGs) and directs a multifaceted antiviral response. ISGs can also be activated through IFN-independent pathways, although the precise mechanisms remain elusive. Here we found that the cytosolic exonuclease Trex1 regulates the activation of a subset of ISGs independently of IFN. Both Trex1(−/−) mouse and TREX1-mutant human cells express high levels of antiviral genes and are refractory to viral infections. The IFN-independent activation of antiviral genes in Trex1(−/−) cells requires STING, TBK1 and IRF3 and IRF7. We also found that Trex1-deficient cells display expanded lysosomal compartment, altered subcellular localization of the transcription factor EB (TFEB), and reduced mTORC1 activity. Together, our data identify Trex1 as a regulator of lysosomal biogenesis and IFN-independent activation of antiviral genes, and shows dysregulation of lysosomes can elicit innate immune responses.",2013 Jan 18,"['Hasan, Maroof', 'Koch, James', 'Rakheja, Dinesh', 'Pattnaik, Asit K.', 'Brugarolas, James', 'Dozmorov, Igor', 'Levine, Beth', 'Wakeland, Edward K.', 'Lee-kirsch, Min Ae', 'Yan, Nan']",Nat Immunol,,,True
fc8ad569b2d40a7af0cdcfa184aa698841e9ef36,PMC,Trex1 regulates lysosomal biogenesis and interferon-independent activation of antiviral genes,http://dx.doi.org/10.1038/ni.2475,PMC3522772,23160154,NO-CC CODE,"Innate immune sensing of viral nucleic acids triggers type I interferon (IFN) production, which activates interferon-stimulated genes (ISGs) and directs a multifaceted antiviral response. ISGs can also be activated through IFN-independent pathways, although the precise mechanisms remain elusive. Here we found that the cytosolic exonuclease Trex1 regulates the activation of a subset of ISGs independently of IFN. Both Trex1(−/−) mouse and TREX1-mutant human cells express high levels of antiviral genes and are refractory to viral infections. The IFN-independent activation of antiviral genes in Trex1(−/−) cells requires STING, TBK1 and IRF3 and IRF7. We also found that Trex1-deficient cells display expanded lysosomal compartment, altered subcellular localization of the transcription factor EB (TFEB), and reduced mTORC1 activity. Together, our data identify Trex1 as a regulator of lysosomal biogenesis and IFN-independent activation of antiviral genes, and shows dysregulation of lysosomes can elicit innate immune responses.",2013 Jan 18,"['Hasan, Maroof', 'Koch, James', 'Rakheja, Dinesh', 'Pattnaik, Asit K.', 'Brugarolas, James', 'Dozmorov, Igor', 'Levine, Beth', 'Wakeland, Edward K.', 'Lee-kirsch, Min Ae', 'Yan, Nan']",Nat Immunol,,,False
9695a8fb288be9ef014dbaf030498d3c7ce0fc81,PMC,Genomic and proteomic approaches for studying human cancer: Prospects for true patient-tailored therapy,http://dx.doi.org/10.1186/1479-7364-1-2-134,PMC3525069,15601541,NO-CC CODE,"Global gene expression analysis is beginning to move from the laboratories of basic investigators to large-scale clinical trials. The potential of this technology to improve diagnosis and tailored treatment of human disease may soon be realised, now that several comprehensive studies have demonstrated the utility of gene expression profiles for the classification of tumours into distinct, clinically relevant subtypes and the prediction of clinical outcomes. In addition, new data from the emerging proteomics platforms add another layer of molecular information to the study of human disease, as scientists attempt to catalogue a complete inventory of the proteins encoded by the genome and to establish a 'biosignature' profile of human health and disease. As a result, it is anticipated that, together, these technologies will facilitate the comprehensive study of genes, gene products and signalling pathways so that the objective of personalised molecular medicine can be achieved. This paper will review the studies that best demonstrate how genomics and proteomics technologies can be used to improve cancer diagnosis and treatment it will specifically highlight the important work being incorporated into clinical trials.",2004 Jan 1,"['Carr, Kristen M', 'Rosenblatt, Kevin', 'Petricoin, Emanuel F', 'Liotta, Lance A']",Hum Genomics,,,True
fab11f842979b0ca95927e6919ed0740a5ccc3be,PMC,Strategies for intranasal delivery of vaccines,http://dx.doi.org/10.1007/s13346-012-0085-z,PMC3539070,23316448,NO-CC CODE,"The vast majority of human pathogens colonize and invade at the mucosal surfaces. Preventing infection at these sites via mucosally active vaccines is a promising and rational approach for vaccine development. However, it is only recently that the stimulation of local immunity at the mucosal surfaces has become a primary objective in addition to inducing systemic immunity. This review describes vaccine formulations designed for mucosal delivery to the nasal-associated lymphoid tissue, via intranasal administration. The association of antigens with mucosal adjuvants and delivery systems is emphasised.",2013 Feb 12,"['Zaman, Mehfuz', 'Chandrudu, Saranya', 'Toth, Istvan']",Drug Deliv Transl Res,,,True
b6641c661abc4e253dac263e658506b83995ec46,PMC,Influenza virus and cell signaling pathways,http://dx.doi.org/10.12659/MSM.881801,PMC3539548,21629204,NO-CC CODE,"Influenza viruses comprise a major class of human respiratory pathogens, responsible for causing morbidity and mortality worldwide. Influenza A virus, due to its segmented RNA genome, is highly subject to mutation, resulting in rapid formation of variants. During influenza infection, viral proteins interact with host proteins and exploit a variety of cellular pathways for their own benefit. Influenza virus inhibits the synthesis of these cellular proteins and facilitates expression of its own proteins for viral transcription and replication. Infected cell pathways are hijacked by an array of intracellular signaling cascades such as NF-κB signaling, PI3K/Akt pathway, MAPK pathway, PKC/PKR signaling and TLR/RIG-I signaling cascades. This review presents a research update on the subject and discusses the impact of influenza viral infection on these cell signaling pathways.",2011 Jun 1,"['Gaur, Pratibha', 'Munjal, Ashok', 'Lal, Sunil K.']",Med Sci Monit,,,True
edc0a7510a126ecbd0c7d43a489979bab36ceea1,PMC,"Publications in ISI-indexed public health journals from mainland China, Hong Kong and Taiwan during 1999–2008",http://dx.doi.org/10.12659/MSM.881832,PMC3539559,21709647,NO-CC CODE,"BACKGROUND: There has been a steady increase in China’s annual research output. We aimed to investigate the research output in public health from 3 major regions of China: mainland China (ML), Hong Kong (HK) and Taiwan (TW). MATERIAL/METHODS: We retrieved papers published in 105 public health-related journals from ML, HK and TW with the applications of the ISI Web of Knowledge database. The total papers, impact factor, times cited, papers published in the highest impact factor journals, and most often published journals were analyzed for quantity and quality comparisons among the 3 regions. RESULTS: Totally, 2587 papers were published during 1999–2008, including 1089 (42.1%) from ML, 471 (18.2%) from HK, and 1027 (39.7%) from TW. The total annual number of papers from the 3 regions increased significantly, from 140 in 1999 to 424 in 2008. The average impact factor of papers from TW (2.588) was higher than those from HK (2.531) and ML (1.568). The average number of times cited of each paper from TW was 8.84, followed by 8.34 from HK and 5.90 from ML. Excluding publications in Biomedical and Environmental Sciences, papers from ML had higher average IF and average times cited. TW had the most articles published in the highest impact factor journals, and HK had the highest total IF of most often published journals. CONCLUSIONS: The total number of papers in public health from China increased significantly during 1999–2008. ML contributed the highest annual paper output compared with HK and TW, but papers from ML are more often locally published and less frequently cited.",2011 Jul 1,"['Zheng, Mei-Ling', 'Yang, Li-Li', 'Shu, Qiang', 'Shen, Yi']",Med Sci Monit,,,True
377d8d4560cb8cca5ca75e49f9f5be8047c767ea,PMC,Predictors of symptoms of posttraumatic stress in Chinese university students during the 2009 H1N1 influenza pandemic,http://dx.doi.org/10.12659/MSM.881836,PMC3539574,21709644,NO-CC CODE,"BACKGROUND: The university environment poses a high risk of spreading infectious diseases, particularly the 2009 pandemic influenza H1N1, as it is a mass gathering place for youth. This study aimed to evaluate the predictors of stress symptoms among Chinese university students during the 2009 H1N1 influenza pandemic. MATERIAL/METHODS: We used a self-reported questionnaire, the PTSD (posttraumatic stress disorder) Checklist-Civilian Version (PCL-C) to evaluate the stress symptoms among Chinese university students from Heilongjiang (n=455), Beijing (n=106), Shanghai (n=419) and Sichuan (n=102). We then analyzed the predictors of stress symptoms. RESULTS: The proportion of university students enrolled in this study who met symptomatic criteria for PTSD was 2% (22 students). The mean PCL-C total score in the sample was 22.09±8.01. The correlational analyses revealed a significant positive relationship between the PCL-C total score and area, and university grade (P<0.01). Moreover, a negative relationship was found between the PCL-C total score and gender, having H1N1 influenza, having family members, friends or acquaintances having H1N1 influenza, and being afraid of H1N1 influenza (P<0.01). The regression analyses showed that in North China, female gender, having H1N1 influenza, having family members or acquaintances with H1N1 influenza, and being afraid of H1N1 influenza were significant predictors of the stress symptoms. CONCLUSIONS: In North China, female gender, having H1N1 influenza, having family members, friends, or acquaintances with H1N1 influenza, and being afraid of H1N1 influenza were significant predictors of the stress symptoms.",2011 Jul 1,"['Xu, Jiahong', 'Zheng, Yayuan', 'Wang, Mingmin', 'Zhao, Jiangmin', 'Zhan, Qing', 'Fu, Mingxu', 'Wang, Qianyi', 'Xiao, Junjie', 'Cheng, Yan']",Med Sci Monit,,,True
1d207b14f92ffce3c151c86f9483c159065e0646,PMC,Natural killer cells act as rheostats modulating anti-viral T cells,http://dx.doi.org/10.1038/nature10624,PMC3539796,22101430,NO-CC CODE,"Anti-viral T cells are thought to regulate whether hepatitis C virus (HCV) and HIV infections result in viral control, asymptomatic persistence, or severe disease, though the reasons for these different outcomes remain unclear. Recent genetic evidence, however, has indicated a correlation between certain natural killer (NK) cell receptors and progression of both HIV and HCV infection(1–3), implying that NK cells are playing a role in these T cell-associated diseases. While direct NK cell-mediated lysis of virus-infected cells may contribute to anti-viral defense during some virus infections, especially murine cytomegalovirus (MCMV) infections in mice and perhaps HIV in humans(4–5), NK cells have also been suspected as having immunoregulatory functions. For instance, NK cells may indirectly regulate T cell responses by lysing MCMV-infected antigen-presenting cells(6–7). In contrast to MCMV, lymphocytic choromeningitis virus (LCMV) infection in mice seems resistant to any direct anti-viral effects of NK cells(5,8). Here the roles of NK cells in regulating T cell-dependent viral persistence and immunopathology were examined in mice infected with LCMV, an established model for HIV and HCV infections in humans. We describe a three-way interaction, whereby activated NK cells cytolytically eliminate activated CD4 T cells that affect CD8 T-cell function and exhaustion. At high virus dose NK cells prevented fatal pathology while enabling T-cell exhaustion and viral persistence, but at a medium dose NK cells paradoxically facilitated lethal T cell-mediated pathology. Thus, NK cells can act as rheostats, regulating CD4 T cell-mediated support for the anti-viral CD8 T cells that control viral pathogenesis and persistence.",2011 Nov 20,"['Waggoner, Stephen N.', 'Cornberg, Markus', 'Selin, Liisa K.', 'Welsh, Raymond M.']",Nature,,,True
09629119b4604ff4655e01d37b0dd0a88bfcc976,PMC,Natural killer cells act as rheostats modulating anti-viral T cells,http://dx.doi.org/10.1038/nature10624,PMC3539796,22101430,NO-CC CODE,"Anti-viral T cells are thought to regulate whether hepatitis C virus (HCV) and HIV infections result in viral control, asymptomatic persistence, or severe disease, though the reasons for these different outcomes remain unclear. Recent genetic evidence, however, has indicated a correlation between certain natural killer (NK) cell receptors and progression of both HIV and HCV infection(1–3), implying that NK cells are playing a role in these T cell-associated diseases. While direct NK cell-mediated lysis of virus-infected cells may contribute to anti-viral defense during some virus infections, especially murine cytomegalovirus (MCMV) infections in mice and perhaps HIV in humans(4–5), NK cells have also been suspected as having immunoregulatory functions. For instance, NK cells may indirectly regulate T cell responses by lysing MCMV-infected antigen-presenting cells(6–7). In contrast to MCMV, lymphocytic choromeningitis virus (LCMV) infection in mice seems resistant to any direct anti-viral effects of NK cells(5,8). Here the roles of NK cells in regulating T cell-dependent viral persistence and immunopathology were examined in mice infected with LCMV, an established model for HIV and HCV infections in humans. We describe a three-way interaction, whereby activated NK cells cytolytically eliminate activated CD4 T cells that affect CD8 T-cell function and exhaustion. At high virus dose NK cells prevented fatal pathology while enabling T-cell exhaustion and viral persistence, but at a medium dose NK cells paradoxically facilitated lethal T cell-mediated pathology. Thus, NK cells can act as rheostats, regulating CD4 T cell-mediated support for the anti-viral CD8 T cells that control viral pathogenesis and persistence.",2011 Nov 20,"['Waggoner, Stephen N.', 'Cornberg, Markus', 'Selin, Liisa K.', 'Welsh, Raymond M.']",Nature,,,False
affffc6dc24b98ff94d3b5ef1f2f3ad1afc5e772,PMC,Natural killer cells act as rheostats modulating anti-viral T cells,http://dx.doi.org/10.1038/nature10624,PMC3539796,22101430,NO-CC CODE,"Anti-viral T cells are thought to regulate whether hepatitis C virus (HCV) and HIV infections result in viral control, asymptomatic persistence, or severe disease, though the reasons for these different outcomes remain unclear. Recent genetic evidence, however, has indicated a correlation between certain natural killer (NK) cell receptors and progression of both HIV and HCV infection(1–3), implying that NK cells are playing a role in these T cell-associated diseases. While direct NK cell-mediated lysis of virus-infected cells may contribute to anti-viral defense during some virus infections, especially murine cytomegalovirus (MCMV) infections in mice and perhaps HIV in humans(4–5), NK cells have also been suspected as having immunoregulatory functions. For instance, NK cells may indirectly regulate T cell responses by lysing MCMV-infected antigen-presenting cells(6–7). In contrast to MCMV, lymphocytic choromeningitis virus (LCMV) infection in mice seems resistant to any direct anti-viral effects of NK cells(5,8). Here the roles of NK cells in regulating T cell-dependent viral persistence and immunopathology were examined in mice infected with LCMV, an established model for HIV and HCV infections in humans. We describe a three-way interaction, whereby activated NK cells cytolytically eliminate activated CD4 T cells that affect CD8 T-cell function and exhaustion. At high virus dose NK cells prevented fatal pathology while enabling T-cell exhaustion and viral persistence, but at a medium dose NK cells paradoxically facilitated lethal T cell-mediated pathology. Thus, NK cells can act as rheostats, regulating CD4 T cell-mediated support for the anti-viral CD8 T cells that control viral pathogenesis and persistence.",2011 Nov 20,"['Waggoner, Stephen N.', 'Cornberg, Markus', 'Selin, Liisa K.', 'Welsh, Raymond M.']",Nature,,,False
fa8e948aec6194e737fbe6273de48cf674a0d363,PMC,Natural killer cells act as rheostats modulating anti-viral T cells,http://dx.doi.org/10.1038/nature10624,PMC3539796,22101430,NO-CC CODE,"Anti-viral T cells are thought to regulate whether hepatitis C virus (HCV) and HIV infections result in viral control, asymptomatic persistence, or severe disease, though the reasons for these different outcomes remain unclear. Recent genetic evidence, however, has indicated a correlation between certain natural killer (NK) cell receptors and progression of both HIV and HCV infection(1–3), implying that NK cells are playing a role in these T cell-associated diseases. While direct NK cell-mediated lysis of virus-infected cells may contribute to anti-viral defense during some virus infections, especially murine cytomegalovirus (MCMV) infections in mice and perhaps HIV in humans(4–5), NK cells have also been suspected as having immunoregulatory functions. For instance, NK cells may indirectly regulate T cell responses by lysing MCMV-infected antigen-presenting cells(6–7). In contrast to MCMV, lymphocytic choromeningitis virus (LCMV) infection in mice seems resistant to any direct anti-viral effects of NK cells(5,8). Here the roles of NK cells in regulating T cell-dependent viral persistence and immunopathology were examined in mice infected with LCMV, an established model for HIV and HCV infections in humans. We describe a three-way interaction, whereby activated NK cells cytolytically eliminate activated CD4 T cells that affect CD8 T-cell function and exhaustion. At high virus dose NK cells prevented fatal pathology while enabling T-cell exhaustion and viral persistence, but at a medium dose NK cells paradoxically facilitated lethal T cell-mediated pathology. Thus, NK cells can act as rheostats, regulating CD4 T cell-mediated support for the anti-viral CD8 T cells that control viral pathogenesis and persistence.",2011 Nov 20,"['Waggoner, Stephen N.', 'Cornberg, Markus', 'Selin, Liisa K.', 'Welsh, Raymond M.']",Nature,,,False
4fc997d9c975d91ab09f8643d90be58e1accb289,PMC,Natural killer cells act as rheostats modulating anti-viral T cells,http://dx.doi.org/10.1038/nature10624,PMC3539796,22101430,NO-CC CODE,"Anti-viral T cells are thought to regulate whether hepatitis C virus (HCV) and HIV infections result in viral control, asymptomatic persistence, or severe disease, though the reasons for these different outcomes remain unclear. Recent genetic evidence, however, has indicated a correlation between certain natural killer (NK) cell receptors and progression of both HIV and HCV infection(1–3), implying that NK cells are playing a role in these T cell-associated diseases. While direct NK cell-mediated lysis of virus-infected cells may contribute to anti-viral defense during some virus infections, especially murine cytomegalovirus (MCMV) infections in mice and perhaps HIV in humans(4–5), NK cells have also been suspected as having immunoregulatory functions. For instance, NK cells may indirectly regulate T cell responses by lysing MCMV-infected antigen-presenting cells(6–7). In contrast to MCMV, lymphocytic choromeningitis virus (LCMV) infection in mice seems resistant to any direct anti-viral effects of NK cells(5,8). Here the roles of NK cells in regulating T cell-dependent viral persistence and immunopathology were examined in mice infected with LCMV, an established model for HIV and HCV infections in humans. We describe a three-way interaction, whereby activated NK cells cytolytically eliminate activated CD4 T cells that affect CD8 T-cell function and exhaustion. At high virus dose NK cells prevented fatal pathology while enabling T-cell exhaustion and viral persistence, but at a medium dose NK cells paradoxically facilitated lethal T cell-mediated pathology. Thus, NK cells can act as rheostats, regulating CD4 T cell-mediated support for the anti-viral CD8 T cells that control viral pathogenesis and persistence.",2011 Nov 20,"['Waggoner, Stephen N.', 'Cornberg, Markus', 'Selin, Liisa K.', 'Welsh, Raymond M.']",Nature,,,False
b9fbd0773ea09b1ad96a7746601d7a8e2125313d,PMC,"Virulent Avian Infectious Bronchitis Virus, People’s Republic of China",http://dx.doi.org/10.3201/eid1812.120552,PMC3557894,23171741,NO-CC CODE,"A virulent avian infectious bronchitis virus (IBV) was isolated from 30-day-old broiler chickens that exhibited respiratory symptoms, nephropathologic lesions, and a high proportion of deaths in the People’s Republic of China during 2005. The strain, designated YN, was genetically and pathologically characterized. Phylogenetic analysis showed that YN and most of the previously characterized IBV isolates found in China were phylogenetically classified into 2 main genetic clusters. The YN isolate caused severe lesions and resulted in deaths of 65% in experimental infections of 30-day-old specific-pathogen–free chickens. Tracheal and severe kidney lesions developed in all infected birds, confirming the ability of YN strain to induce both respiratory and renal disease. IBV antigens were detected by immunohistochemical analysis in the trachea, lung, kidney, and bursa, consistent with histopathologic observations, virus isolation, and reverse transcription PCR detection. We showed that YN IBV exhibits severe pathogenicity in chickens, and that similar viruses are prevalent in China.",2012 Dec,"['Feng, Jinling', 'Hu, Yanxin', 'Ma, Zhijun', 'Yu, Qi', 'Zhao, Jixun', 'Liu, Xiaodong', 'Zhang, Guozhong']",Emerg Infect Dis,,,True
e7d09bd9d2aa4dd46ffe54edc2526bf46aa281b6,PMC,"Virulent Avian Infectious Bronchitis Virus, People’s Republic of China",http://dx.doi.org/10.3201/eid1812.120552,PMC3557894,23171741,NO-CC CODE,"A virulent avian infectious bronchitis virus (IBV) was isolated from 30-day-old broiler chickens that exhibited respiratory symptoms, nephropathologic lesions, and a high proportion of deaths in the People’s Republic of China during 2005. The strain, designated YN, was genetically and pathologically characterized. Phylogenetic analysis showed that YN and most of the previously characterized IBV isolates found in China were phylogenetically classified into 2 main genetic clusters. The YN isolate caused severe lesions and resulted in deaths of 65% in experimental infections of 30-day-old specific-pathogen–free chickens. Tracheal and severe kidney lesions developed in all infected birds, confirming the ability of YN strain to induce both respiratory and renal disease. IBV antigens were detected by immunohistochemical analysis in the trachea, lung, kidney, and bursa, consistent with histopathologic observations, virus isolation, and reverse transcription PCR detection. We showed that YN IBV exhibits severe pathogenicity in chickens, and that similar viruses are prevalent in China.",2012 Dec,"['Feng, Jinling', 'Hu, Yanxin', 'Ma, Zhijun', 'Yu, Qi', 'Zhao, Jixun', 'Liu, Xiaodong', 'Zhang, Guozhong']",Emerg Infect Dis,,,False
916602c93360fa550e272dcc72f00bd36be64817,PMC,"Lessons from the History of Quarantine, from Plague to Influenza A",http://dx.doi.org/10.3201/eid1902.120312,PMC3559034,23343512,NO-CC CODE,"In the new millennium, the centuries-old strategy of quarantine is becoming a powerful component of the public health response to emerging and reemerging infectious diseases. During the 2003 pandemic of severe acute respiratory syndrome, the use of quarantine, border controls, contact tracing, and surveillance proved effective in containing the global threat in just over 3 months. For centuries, these practices have been the cornerstone of organized responses to infectious disease outbreaks. However, the use of quarantine and other measures for controlling epidemic diseases has always been controversial because such strategies raise political, ethical, and socioeconomic issues and require a careful balance between public interest and individual rights. In a globalized world that is becoming ever more vulnerable to communicable diseases, a historical perspective can help clarify the use and implications of a still-valid public health strategy.",2013 Feb,"Tognotti, Eugenia",Emerg Infect Dis,,,True
2abeedc1200b3978f52e87ebeb9e0fa0ae56aa6f,PMC,"Lessons from the History of Quarantine, from Plague to Influenza A",http://dx.doi.org/10.3201/eid1902.120312,PMC3559034,23343512,NO-CC CODE,"In the new millennium, the centuries-old strategy of quarantine is becoming a powerful component of the public health response to emerging and reemerging infectious diseases. During the 2003 pandemic of severe acute respiratory syndrome, the use of quarantine, border controls, contact tracing, and surveillance proved effective in containing the global threat in just over 3 months. For centuries, these practices have been the cornerstone of organized responses to infectious disease outbreaks. However, the use of quarantine and other measures for controlling epidemic diseases has always been controversial because such strategies raise political, ethical, and socioeconomic issues and require a careful balance between public interest and individual rights. In a globalized world that is becoming ever more vulnerable to communicable diseases, a historical perspective can help clarify the use and implications of a still-valid public health strategy.",2013 Feb,"Tognotti, Eugenia",Emerg Infect Dis,,,False
e1c75a638bdac1693aee9103d38374e401253704,PMC,"Nipah Virus Infection Outbreak with Nosocomial and Corpse-to-Human Transmission, Bangladesh",http://dx.doi.org/10.3201/eid1902.120971,PMC3559054,23347678,NO-CC CODE,"Active Nipah virus encephalitis surveillance identified an encephalitis cluster and sporadic cases in Faridpur, Bangladesh, in January 2010. We identified 16 case-patients; 14 of these patients died. For 1 case-patient, the only known exposure was hugging a deceased patient with a probable case, while another case-patient’s exposure involved preparing the same corpse for burial by removing oral secretions and anogenital excreta with a cloth and bare hands. Among 7 persons with confirmed sporadic cases, 6 died, including a physician who had physically examined encephalitis patients without gloves or a mask. Nipah virus–infected patients were more likely than community-based controls to report drinking raw date palm sap and to have had physical contact with an encephalitis patient (29% vs. 4%, matched odds ratio undefined). Efforts to prevent transmission should focus on reducing caregivers’ exposure to infected patients’ bodily secretions during care and traditional burial practices.",2013 Feb,"['Sazzad, Hossain M.S.', 'Hossain, M. Jahangir', 'Gurley, Emily S.', 'Ameen, Kazi M.H.', 'Parveen, Shahana', 'Islam, M. Saiful', 'Faruque, Labib I.', 'Podder, Goutam', 'Banu, Sultana S.', 'Lo, Michael K.', 'Rollin, Pierre E.', 'Rota, Paul A.', 'Daszak, Peter', 'Rahman, Mahmudur', 'Luby, Stephen P.']",Emerg Infect Dis,,,True
ffd3a93b927e221ded4cf76536ad31bef2c74b89,PMC,"Fatal Respiratory Infections Associated with Rhinovirus Outbreak, Vietnam",http://dx.doi.org/10.3201/eid1811.120607,PMC3559162,23092635,NO-CC CODE,"During an outbreak of severe acute respiratory infections in 2 orphanages, Vietnam, 7/12 hospitalized children died. All hospitalized children and 26/43 children from outbreak orphanages tested positive for rhinovirus versus 9/40 control children (p = 0.0005). Outbreak rhinoviruses formed a distinct genetic cluster. Human rhinovirus is an underappreciated cause of severe pneumonia in vulnerable groups.",2012 Nov,"['Hai, Le Thanh', 'Bich, Vu Thi Ngoc', 'Ngai, Le Kien', 'Diep, Nguyen Thi Ngoc', 'Phuc, Phan Huu', 'Hung, Viet Pham', 'Taylor, Walter R.', 'Horby, Peter', 'Liem, Nguyen Thanh', 'Wertheim, Heiman F.L.']",Emerg Infect Dis,,,True
f5a95ba3b592c46903d5f4a4c00bd15a2cbb74f9,PMC,"Influenza vaccines and vaccinations in Poland – past, present and future",http://dx.doi.org/10.12659/MSM.883534,PMC3560607,23111751,NO-CC CODE,"Influenza causes seasonal infections worldwide that can lead to complications and deaths in every age group. The most effective and cheapest way to combat influenza is through vaccination. In many countries, including Poland, for each age group, the rate of vaccination against influenza is still at a very low level, which generates high social costs, not infrequently family tragedies in the case of irreversible complications of influenza, or death of a loved one. Regular vaccination should be part of good medical practice, as well as an individual’s engagement in their own health and in that of their family. Based on numerous studies, it is estimated that the effectiveness of current inactivated influenza vaccine in reducing morbidity and mortality in high-risk groups ranges from 50–70%. According to data from the National Institute of Public Health-National Institute of Hygiene, the rate of vaccination in children in 2008 in Poland was very low. In the group of children aged from 6 months to 14 years, only 1.1–1.6% were vaccinated. Although influenza vaccination for people aged over 65 years was free of charge in many provinces in this group, only 13.4% of this population was immunized, while in the case of people with chronic diseases, only 11.1% were immunized. The vaccination rate among health care employees is an embarrassing 6.4%. More educational activities addressed to both medical professionals and patients are required in order to increase influenza vaccine coverage in Poland.",2012 Nov 1,"['Brydak, Lidia B.', 'Kosek, Agnieszka WoŸniak', 'Nitsch-Osuch, Aneta']",Med Sci Monit,,,True
3741c1d2fb8893ca57a949704a64a7a570802543,PMC,High-throughput virtual screening and docking studies of matrix protein vp40 of ebola virus,http://dx.doi.org/10.6026/97320630009286,PMC3607187,23559747,NO-CC CODE,"Ebolavirus, a member of the Filoviridae family of negative-sense RNA viruses, causes severe haemorrhagic fever leading up to 90% lethality. Ebolavirus matrix protein VP40 is involved in the virus assembly and budding process. The RNA binding pocket of VP40 is considered as the drug target site for structure based drug design. High Throughput Virtual Screening and molecular docking studies were employed to find the suitable inhibitors against VP40. Ten compounds showing good glide score and glide energy as well as interaction with specific amino acid residues were short listed as drug leads. These small molecule inhibitors could be potent inhibitors for VP40 matrix protein by blocking virus assembly and budding process.",2013 Mar 19,"['Tamilvanan, Thangaraju', 'Hopper, Waheeta']",Bioinformation,,,True
20b18e7a91ce0a4df5d1411869174a4bff4bb3a8,PMC,High-throughput virtual screening and docking studies of matrix protein vp40 of ebola virus,http://dx.doi.org/10.6026/97320630009286,PMC3607187,23559747,NO-CC CODE,"Ebolavirus, a member of the Filoviridae family of negative-sense RNA viruses, causes severe haemorrhagic fever leading up to 90% lethality. Ebolavirus matrix protein VP40 is involved in the virus assembly and budding process. The RNA binding pocket of VP40 is considered as the drug target site for structure based drug design. High Throughput Virtual Screening and molecular docking studies were employed to find the suitable inhibitors against VP40. Ten compounds showing good glide score and glide energy as well as interaction with specific amino acid residues were short listed as drug leads. These small molecule inhibitors could be potent inhibitors for VP40 matrix protein by blocking virus assembly and budding process.",2013 Mar 19,"['Tamilvanan, Thangaraju', 'Hopper, Waheeta']",Bioinformation,,,False
863fec2f2894a48b0dbf00f4b934f75a002a9941,PMC,A novel submicron emulsion system loaded with vincristine–oleic acid ion-pair complex with improved anticancer effect: in vitro and in vivo studies,http://dx.doi.org/10.2147/IJN.S41775,PMC3607420,23658485,NO-CC CODE,"BACKGROUND: Vincristine (VCR), which is a widely used antineoplastic drug, was integrated with a submicron-emulsion drug-delivery system to enhance the anticancer effect. METHODS: After the formation of a VCR-oleic acid ion-pair complex (VCR-OA), the VCR-OA-loaded submicron emulsion (VCR-OA-SME), prepared by classical high-pressure homogenization, was characterized and its in vitro anticancer effects were evaluated. RESULTS: The submicron-emulsion formulation exhibited a homogeneous round shape. The mean particle size, zeta potential, and encapsulation efficiency were 157.6 ± 12.6 nm, −26.5 ± 5.0 mV and 78.64% ± 3.44%, respectively. An in vitro release study of the VCR-OA-SME revealed that 12.4% of the VCR was released within the first 2 hours (initial burst-release phase) and the rest of the drug was detected in the subsequent sustained-release phase. Compared with VCR solution, the pharmacokinetic study of VCR-OA-SME showed relatively longer mean residence time (mean residence time [0–∞] increased from 187.19 to 227.56 minutes), higher maximum concentration (from 252.13 ng/mL to 533.34 ng/mL), and greater area under the curve (area under the curve [0–∞] from 11,417.77 μg/L/minute to 17,164.34 μg/L/minute. Moreover, the VCR-OA-SME exhibited higher cytotoxicity (P < 0.05) on tumor cells by inducing cell arrest in the G2/M phase or even apoptosis (P < 0.05). CONCLUSION: The VCR-OA-SME formulation in our study displayed great potential for an anticancer effect for VCR.",2013 Mar 20,"['Zhang, Ting', 'Zheng, Yong', 'Peng, Qiang', 'Cao, Xi', 'Gong, Tao', 'Zhang, Zhirong']",Int J Nanomedicine,,,True
ffae8c96650c55c0edd325fb8ad79010a983c47a,PMC,Genetic variation analysis of reemerging porcine epidemic diarrhea virus prevailing in central China from 2010 to 2011,http://dx.doi.org/10.1007/s11262-012-0867-x,PMC3610022,23269482,NO-CC CODE,"Porcine epidemic diarrhea has re-emerged with devastating impact in central China since October 2010. To investigate and analyze the reason of this outbreak, the M and ORF3 genes of 15 porcine epidemic diarrhea viruses (PEDV), which were collected from different areas of central China during October 2010 and December 2011, were amplified by reverse transcriptase polymerase chain reaction, cloned, sequenced, and analyzed. Sequence analyses showed that the nucleotides and amino acids were changed at some sites in the M and ORF3 genes of the 15 PEDV strains compared with those genes of CV777 reference strain. Based on the phylogenetic analyses, PEDVs in central China and reference strains could be separated into three groups: G1, G2, and G3. The 15 PEDV strains belonged to G3 group and showed a close relationship with Korean strains (2007), Thai strains (2007–2008), and partial other Chinese strains (2010–2011), but differed genetically from European strains (Br1/87) and the vaccine strain (CV777 vs) being used in China. Furthermore, all 15 PEDV strains from central China and some other isolates in China from 2003 to 2007 (LJB-03, QH, and LZC) belonged to different group. Therefore, PEDV exhibits rapid variation and genetic evolution, and the currently prevailing PEDV strains in central China are a new genotype.",2013 Apr 27,"['Yang, Xia', 'Huo, Jin-yao', 'Chen, Lu', 'Zheng, Feng-mei', 'Chang, Hong-tao', 'Zhao, Jun', 'Wang, Xin-wei', 'Wang, Chuan-qing']",Virus Genes,,,False
c4f1924395fe010018f7e83f71f5a0ba744dcf2e,PMC,Lactate dehydrogenase as a marker of nasopharyngeal inflammatory injury during viral upper respiratory infection: implications for acute otitis media,http://dx.doi.org/10.1038/pr.2012.179,PMC3612027,23202721,NO-CC CODE,"BACKGROUND: Acute otitis media (AOM) is a frequent complication of viral upper respiratory tract infection (URI). We hypothesized that severity of nasopharyngeal cellular injury during URI, as measured by lactate dehydrogenase (LDH) concentrations in nasopharyngeal secretions (NPS), is related to AOM complication. METHODS: LDH concentrations were determined in NPS samples (n=594) which were collected at the initial visit for URI from 183 children who were followed for development of AOM. A subset of NPS samples (n= 134) were analyzed for interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) α concentrations. RESULTS: AOM complication was independently predicted by LDH concentrations (median mU/ml with AOM = 2438 vs. without AOM = 1573, estimate=0.276; P=0.02). LDH effect on AOM development was highest during the first 4 days of URI. LDH concentrations were higher in URIs due to adenoviruses, bocaviruses, and rhinoviruses when compared to virus-negative samples (P <0.05). There was a positive correlation between concentrations of LDH and all cytokines (P< 0.001). CONCLUSION: LDH concentrations in NPS are positively associated with AOM risk, suggesting that the severity of nasopharyngeal inflammatory injury during URI contributes to the development of AOM, and that reduction of inflammatory injury may reduce the risk for AOM.",2013 Mar 30,"['Ede, Linda C.', 'O’Brien, James', 'Chonmaitree, Tasnee', 'Han, Yimei', 'Patel, Janak A.']",Pediatr Res,,,True
431cc0d8bd58bdbe9da45c4402399713d1a882ae,PMC,An Informatics Solution for Informing Care Delivery of Immediate Public Health Risks to Their Patients,http://dx.doi.org/10.5210/ojphi.v1i1.2750,PMC3615750,23569573,NO-CC CODE,"This paper describes a public health alerting approach that has the potential to improve patient care during a public health outbreak and reduce healthcare costs, streamline the process of public health alert management and dissemination, and heighten the crucial feedback loop between public health officials and clinicians. The approach ties public health alerts into the diagnostic process and allows clinicians to more easily determine when an observed medical condition may be related to a more widespread disease outbreak. A prototype Alert Knowledge Repository (AKR) service using this approach was demonstrated within the Health Information and Management Systems Society (HIMSS) and the Public Health Information Network (PHIN) interoperability showcases in April and September 2009, respectively.",2009 Dec 10,"['Lombardo, Joseph S', 'Garrett, Nedra', 'Loschen, Wayne', 'Seagraves, Richard', 'Nichols, Barbara', 'Babin, Steven']",Online J Public Health Inform,,,True
fc7a909258427d608f8f8e3a4d2f3d7ef1dba473,PMC,Advanced Querying Features for Disease Surveillance Systems,http://dx.doi.org/10.5210/ojphi.v2i1.2847,PMC3615752,23569575,NO-CC CODE,"Most automated disease surveillance systems notify users of increases in the prevalence of reports in syndrome categories and allow users to view patient level data related to those increases. Occasionally, a more dynamic level of control is required to properly detect an emerging disease in a community. Dynamic querying features are invaluable when using existing surveillance systems to investigate outbreaks of newly emergent diseases or to identify cases of reportable diseases within data being captured for surveillance. The objective of the Advance Querying Tool (AQT) is to build a more flexible query interface for most web-based disease surveillance systems. This interface allows users to define and build their query as if they were writing a logical expression for a mathematical computation. The AQT allows users to develop, investigate, save, and share complex case definitions. It provides a flexible interface that accommodates both advanced and novice users, checks the validity of the expression as it is built, and marks errors for users.",2010 Apr 9,"Hashemian, Mohammad R.",Online J Public Health Inform,,,True
14180d7522cd39919afbfe4a6725e1cfc51229bc,PMC,Spatial and Temporal Algorithm Evaluation for Detecting Over-The-Counter Thermometer Sale Increases during 2009 H1N1 Pandemic,http://dx.doi.org/10.5210/ojphi.v4i1.3915,PMC3615801,23569624,NO-CC CODE,"BACKGROUND: Spatial outbreak detection algorithms using routinely collected healthcare data have been developed since the late 90s to identify and locate disease outbreaks. However, current well-received spatial algorithms assume only one outbreak cluster present at the same point of time which may not be valid during a pandemic when several clusters of geographic areas concurrently occur. Based on a retrospective evaluation on time-series and spatial algorithms, this paper suggests that time series analysis in detection of pandemics is still a desirable process, which may achieve more sensitive performance with better timeliness. METHODS: In this paper, we first prove in theory that two existing spatial models, the likelihood ratio and the Bayesian spatial scan statistics, are not useful if multiple clusters occur at the same point of time in different geographic regions. Then we conduct a comparison between a spatial algorithm, the Bayesian Spatial Scan Statistic (BSS), and a time series algorithm, the wavelet anomaly detector (WAD), on the performance of detecting the increase of the over-the-counter (OTC) medicine sales during 2009 H1N1 pandemic. RESULTS: The experiments demonstrated that the Bayesian spatial algorithm responded to the increase of thermometer sales about 3 days later than the time series algorithm. CONCLUSION: Time-series algorithms demonstrated an advantage for early outbreak detection, especially when multiple clusters occur at the same time in different geographic regions. Given spatial-temporal algorithms for outbreak detection are widely used, this paper suggests that epidemiologists or public health officials would benefit by applying time series algorithms as a complement to spatial algorithms for public health surveillance.",2012 May 17,"['Que, Jialan', 'Tsui, Fu-Chiang']",Online J Public Health Inform,,,True
33ca94e310160a0d80e15f1d2bbd2379485789d7,PMC,This Zoonotic World,http://dx.doi.org/10.4269/ajtmh.13-0092,PMC3617873,29624312,NO-CC CODE,,2013 Apr 3,"Panosian Dunavan, Claire",Am J Trop Med Hyg,,,True
0b3d08dea77cc6eb97d674682c1a4eb6145940a1,PMC,Differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive stranded RNA viruses,http://dx.doi.org/10.1038/nm.3108,PMC3618596,23455712,NO-CC CODE,"Although susceptibility of neurons in the brain to microbial infection is a major determinant of clinical outcome, little is known about the molecular factors governing this. Here, we show that two types of neurons from distinct brain regions exhibited differential permissivity to replication of several positive-stranded RNA viruses. Granule cell neurons (GCN) of the cerebellum and cortical neurons (CN) from the cerebral cortex have unique innate immune programs that confer differential susceptibility to viral infection ex vivo and in vivo. By transducing CN with genes that were expressed more highly in GCN, we identified three interferon-stimulated genes (ISGs; Ifi27, Irg1, and Rsad2/Viperin) that mediated antiviral effects against different neurotropic viruses. Moreover, we found that the epigenetic state and microRNA-mediated regulation of ISGs correlates with enhanced antiviral response in GCN. Thus, neurons from evolutionarily distinct brain regions have unique innate immune signatures, which likely contribute to their relative permissiveness to infection.",2013 Apr 3,"['Cho, Hyelim', 'Proll, Sean C.', 'Szretter, Kristy J.', 'Katze, Michael G.', 'Gale, Michael', 'Diamond, Michael S.']",Nat Med,,,True
7ea8a6e74e46f70f70c151746ef2df2bada07216,PMC,Differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive stranded RNA viruses,http://dx.doi.org/10.1038/nm.3108,PMC3618596,23455712,NO-CC CODE,"Although susceptibility of neurons in the brain to microbial infection is a major determinant of clinical outcome, little is known about the molecular factors governing this. Here, we show that two types of neurons from distinct brain regions exhibited differential permissivity to replication of several positive-stranded RNA viruses. Granule cell neurons (GCN) of the cerebellum and cortical neurons (CN) from the cerebral cortex have unique innate immune programs that confer differential susceptibility to viral infection ex vivo and in vivo. By transducing CN with genes that were expressed more highly in GCN, we identified three interferon-stimulated genes (ISGs; Ifi27, Irg1, and Rsad2/Viperin) that mediated antiviral effects against different neurotropic viruses. Moreover, we found that the epigenetic state and microRNA-mediated regulation of ISGs correlates with enhanced antiviral response in GCN. Thus, neurons from evolutionarily distinct brain regions have unique innate immune signatures, which likely contribute to their relative permissiveness to infection.",2013 Apr 3,"['Cho, Hyelim', 'Proll, Sean C.', 'Szretter, Kristy J.', 'Katze, Michael G.', 'Gale, Michael', 'Diamond, Michael S.']",Nat Med,,,True
f76c950c5c0544362b9bc72614a3f318da4a4076,PMC,Find novel dual-agonist drugs for treating type 2 diabetes by means of cheminformatics,http://dx.doi.org/10.2147/DDDT.S42113,PMC3623550,23630413,NO-CC CODE,"The high prevalence of type 2 diabetes mellitus in the world as well as the increasing reports about the adverse side effects of the existing diabetes treatment drugs have made developing new and effective drugs against the disease a very high priority. In this study, we report ten novel compounds found by targeting peroxisome proliferator-activated receptors (PPARs) using virtual screening and core hopping approaches. PPARs have drawn increasing attention for developing novel drugs to treat diabetes due to their unique functions in regulating glucose, lipid, and cholesterol metabolism. The reported compounds are featured with dual functions, and hence belong to the category of dual agonists. Compared with the single PPAR agonists, the dual PPAR agonists, formed by combining the lipid benefit of PPARα agonists (such as fibrates) and the glycemic advantages of the PPARγ agonists (such as thiazolidinediones), are much more powerful in treating diabetes because they can enhance metabolic effects while minimizing the side effects. This was observed in the studies on molecular dynamics simulations, as well as on absorption, distribution, metabolism, and excretion, that these novel dual agonists not only possessed the same function as ragaglitazar (an investigational drug developed by Novo Nordisk for treating type 2 diabetes) did in activating PPARα and PPARγ, but they also had more favorable conformation for binding to the two receptors. Moreover, the residues involved in forming the binding pockets of PPARα and PPARγ among the top ten compounds are explicitly presented, and this will be very useful for the in-depth conduction of mutagenesis experiments. It is anticipated that the ten compounds may become potential drug candidates, or at the very least, the findings reported here may stimulate new strategies or provide useful insights for designing new and more powerful dual-agonist drugs for treating type 2 diabetes.",2013 Apr 8,"['Liu, Lei', 'Ma, Ying', 'Wang, Run-Ling', 'Xu, Wei-Ren', 'Wang, Shu-Qing', 'Chou, Kuo-Chen']",Drug Des Devel Ther,,,True
76bd7e45c1c026b89423857cad797033b30aca39,PMC,"Early Introduction and Delayed Dissemination of Pandemic Influenza, Gabon",http://dx.doi.org/10.3201/eid1904.111925,PMC3647404,23631999,NO-CC CODE,"Active surveillance in health care centers in Gabon during 2009–2011 detected 72 clinical cases of pandemic (H1N1) 2009 (pH1N1). We found that pH1N1 virus was introduced in mid-2009 but spread throughout the country in 2010. Thus, Gabon was also affected by pH1N1.",2013 Apr,"['Lekana-Douki, Sonia Etenna', 'Mouinga-Ondémé, Augustin', 'Nkoghe, Dieudonné', 'Drosten, Christian', 'Drexler, Jan Felix', 'Kazanji, Mirdad', 'Leroy, Eric M.']",Emerg Infect Dis,,,True
bc652839250b03af000623dec894399f63d8203b,PMC,Circovirus in Tissues of Dogs with Vasculitis and Hemorrhage,http://dx.doi.org/10.3201/eid1904.121390,PMC3647419,23628223,NO-CC CODE,"We characterized the complete genome of a novel dog circovirus (DogCV) from the liver of a dog with severe hemorrhagic gastroenteritis, vasculitis, and granulomatous lymphadenitis. DogCV was detected by PCR in fecal samples from 19/168 (11.3%) dogs with diarrhea and 14/204 (6.9%) healthy dogs and in blood from 19/409 (3.3%) of dogs with thrombocytopenia and neutropenia, fever of unknown origin, or past tick bite. Co-infection with other canine pathogens was detected for 13/19 (68%) DogCV-positive dogs with diarrhea. DogCV capsid proteins from different dogs varied by up to 8%. In situ hybridization and transmission electron microscopy detected DogCV in the lymph nodes and spleens of 4 dogs with vascular compromise and histiocytic inflammation. The detection of a circovirus in tissues of dogs expands the known tropism of these viruses to a second mammalian host. Our results indicate that circovirus, alone or in co-infection with other pathogens, might contribute to illness and death in dogs.",2013 Apr,"['Li, Linlin', 'McGraw, Sabrina', 'Zhu, Kevin', 'Leutenegger, Christian M.', 'Marks, Stanley L.', 'Kubiski, Steven', 'Gaffney, Patricia', 'Dela Cruz Jr, Florante N.', 'Wang, Chunlin', 'Delwart, Eric', 'Pesavento, Patricia A.']",Emerg Infect Dis,,,True
d64ec639ed9aee0bbfb01e5fbeaeb8c88c6d810e,PMC,"Novel Molecular Type of Clostridium difficile in Neonatal Pigs, Western Australia",http://dx.doi.org/10.3201/eid1905.121062,PMC3647499,23697508,NO-CC CODE,"Clostridium difficile causes neonatal enteritis in piglets; strains of PCR ribotype 078 are most commonly identified. We investigated C. difficile prevalence in piglets in Australia and isolated a novel strain with a unique pathogenicity locus. In a mouse infection model, this strain produced more weight loss than did a ribotype 078 strain.",2013 May,"['Squire, Michele M.', 'Carter, Glen P.', 'Mackin, Kate E.', 'Chakravorty, Anjana', 'Norén, Torbjörn', 'Elliott, Briony', 'Lyras, Dena', 'Riley, Thomas V.']",Emerg Infect Dis,,,True
3de1a5a224b154bb91728f71697ca7bd3db17ee5,PMC,"Novel Lyssavirus in Bat, Spain",http://dx.doi.org/10.3201/eid1905.121071,PMC3647500,23648051,NO-CC CODE,"A new tentative lyssavirus, Lleida bat lyssavirus, was found in a bent-winged bat (Miniopterus schreibersii) in Spain. It does not belong to phylogroups I or II, and it seems to be more closely related to the West Causasian bat virus, and especially to the Ikoma lyssavirus.",2013 May,"['Ceballos, Nidia Aréchiga', 'Morón, Sonia Vázquez', 'Berciano, José M.', 'Nicolás, Olga', 'López, Carolina Aznar', 'Juste, Javier', 'Nevado, Cristina Rodríguez', 'Setién, Álvaro Aguilar', 'Echevarría, Juan E.']",Emerg Infect Dis,,,True
e8aba212b12646260213688399d736da078dd22a,PMC,"Novel Lyssavirus in Bat, Spain",http://dx.doi.org/10.3201/eid1905.121071,PMC3647500,23648051,NO-CC CODE,"A new tentative lyssavirus, Lleida bat lyssavirus, was found in a bent-winged bat (Miniopterus schreibersii) in Spain. It does not belong to phylogroups I or II, and it seems to be more closely related to the West Causasian bat virus, and especially to the Ikoma lyssavirus.",2013 May,"['Ceballos, Nidia Aréchiga', 'Morón, Sonia Vázquez', 'Berciano, José M.', 'Nicolás, Olga', 'López, Carolina Aznar', 'Juste, Javier', 'Nevado, Cristina Rodríguez', 'Setién, Álvaro Aguilar', 'Echevarría, Juan E.']",Emerg Infect Dis,,,False
2f56502b1b23bd52dcf3e700ff370667fac055ee,PMC,Full-Genome Deep Sequencing and Phylogenetic Analysis of Novel Human Betacoronavirus,http://dx.doi.org/10.3201/eid1905.130057,PMC3647518,23693015,NO-CC CODE,"A novel betacoronavirus associated with lethal respiratory and renal complications was recently identified in patients from several countries in the Middle East. We report the deep genome sequencing of the virus directly from a patient’s sputum sample. Our high-throughput sequencing yielded a substantial depth of genome sequence assembly and showed the minority viral variants in the specimen. Detailed phylogenetic analysis of the virus genome (England/Qatar/2012) revealed its close relationship to European bat coronaviruses circulating among the bat species of the Vespertilionidae family. Molecular clock analysis showed that the 2 human infections of this betacoronavirus in June 2012 (EMC/2012) and September 2012 (England/Qatar/2012) share a common virus ancestor most likely considerably before early 2012, suggesting the human diversity is the result of multiple zoonotic events.",2013 May,"['Cotten, Matthew', 'Lam, Tommy T.', 'Watson, Simon J.', 'Palser, Anne L.', 'Petrova, Velislava', 'Grant, Paul', 'Pybus, Oliver G.', 'Rambaut, Andrew', 'Guan, Yi', 'Pillay, Deenan', 'Kellam, Paul', 'Nastouli, Eleni']",Emerg Infect Dis,,,True
167d0e9f3c37038289d218171597deca49fdc0d2,PMC,Full-Genome Deep Sequencing and Phylogenetic Analysis of Novel Human Betacoronavirus,http://dx.doi.org/10.3201/eid1905.130057,PMC3647518,23693015,NO-CC CODE,"A novel betacoronavirus associated with lethal respiratory and renal complications was recently identified in patients from several countries in the Middle East. We report the deep genome sequencing of the virus directly from a patient’s sputum sample. Our high-throughput sequencing yielded a substantial depth of genome sequence assembly and showed the minority viral variants in the specimen. Detailed phylogenetic analysis of the virus genome (England/Qatar/2012) revealed its close relationship to European bat coronaviruses circulating among the bat species of the Vespertilionidae family. Molecular clock analysis showed that the 2 human infections of this betacoronavirus in June 2012 (EMC/2012) and September 2012 (England/Qatar/2012) share a common virus ancestor most likely considerably before early 2012, suggesting the human diversity is the result of multiple zoonotic events.",2013 May,"['Cotten, Matthew', 'Lam, Tommy T.', 'Watson, Simon J.', 'Palser, Anne L.', 'Petrova, Velislava', 'Grant, Paul', 'Pybus, Oliver G.', 'Rambaut, Andrew', 'Guan, Yi', 'Pillay, Deenan', 'Kellam, Paul', 'Nastouli, Eleni']",Emerg Infect Dis,,,False
9456caa4e69d2efb19a1dccca6a307bee16548ea,PMC,"Human Betacoronavirus 2c EMC/2012–related Viruses in Bats, Ghana and Europe",http://dx.doi.org/10.3201/eid1903.121503,PMC3647674,23622767,NO-CC CODE,"We screened fecal specimens of 4,758 bats from Ghana and 272 bats from 4 European countries for betacoronaviruses. Viruses related to the novel human betacoronavirus EMC/2012 were detected in 46 (24.9%) of 185 Nycteris bats and 40 (14.7%) of 272 Pipistrellus bats. Their genetic relatedness indicated EMC/2012 originated from bats.",2013 Mar,"['Annan, Augustina', 'Baldwin, Heather J.', 'Corman, Victor Max', 'Klose, Stefan M.', 'Owusu, Michael', 'Nkrumah, Evans Ewald', 'Badu, Ebenezer Kofi', 'Anti, Priscilla', 'Agbenyega, Olivia', 'Meyer, Benjamin', 'Oppong, Samuel', 'Sarkodie, Yaw Adu', 'Kalko, Elisabeth K.V.', 'Lina, Peter H.C.', 'Godlevska, Elena V.', 'Reusken, Chantal', 'Seebens, Antje', 'Gloza-Rausch, Florian', 'Vallo, Peter', 'Tschapka, Marco', 'Drosten, Christian', 'Drexler, Jan Felix']",Emerg Infect Dis,,,True
a8f2b244f8cc8ecb5129f6ef67640ddd0497ac63,PMC,"Human Betacoronavirus 2c EMC/2012–related Viruses in Bats, Ghana and Europe",http://dx.doi.org/10.3201/eid1903.121503,PMC3647674,23622767,NO-CC CODE,"We screened fecal specimens of 4,758 bats from Ghana and 272 bats from 4 European countries for betacoronaviruses. Viruses related to the novel human betacoronavirus EMC/2012 were detected in 46 (24.9%) of 185 Nycteris bats and 40 (14.7%) of 272 Pipistrellus bats. Their genetic relatedness indicated EMC/2012 originated from bats.",2013 Mar,"['Annan, Augustina', 'Baldwin, Heather J.', 'Corman, Victor Max', 'Klose, Stefan M.', 'Owusu, Michael', 'Nkrumah, Evans Ewald', 'Badu, Ebenezer Kofi', 'Anti, Priscilla', 'Agbenyega, Olivia', 'Meyer, Benjamin', 'Oppong, Samuel', 'Sarkodie, Yaw Adu', 'Kalko, Elisabeth K.V.', 'Lina, Peter H.C.', 'Godlevska, Elena V.', 'Reusken, Chantal', 'Seebens, Antje', 'Gloza-Rausch, Florian', 'Vallo, Peter', 'Tschapka, Marco', 'Drosten, Christian', 'Drexler, Jan Felix']",Emerg Infect Dis,,,False
2e8fb12daa448c956d8b7b348df5e46d29c5f51a,PMC,Detection of Spliced mRNA from Human Bocavirus 1 in Clinical Samples from Children with Respiratory Tract Infections,http://dx.doi.org/10.3201/eid1904.121775,PMC3647721,23628409,NO-CC CODE,"Human bocavirus 1 (HBoV1) is a parvovirus associated with respiratory tract infections (RTIs) in children, but a causal relation has not yet been confirmed. To develop a qualitative reverse transcription PCR to detect spliced mRNA from HBoV1 and to determine whether HBoV1 mRNA correlated better with RTIs than did HBoV1 DNA, we used samples from HBoV1 DNA–positive children, with and without RTIs, to evaluate the test. A real-time reverse transcription PCR, targeting 2 alternatively spliced mRNAs, was developed. HBoV1 mRNA was detected in nasopharyngeal aspirates from 33 (25%) of 133 children with RTIs but in none of 28 controls (p<0.001). The analytical sensitivity and specificity of the test were good. Our data support the hypothesis that HBoV1 may cause RTIs, and we propose that HBoV1 mRNA could be used with benefit, instead of HBoV1 DNA, as a diagnostic target.",2013 Apr,"['Christensen, Andreas', 'Døllner, Henrik', 'Skanke, Lars Høsøien', 'Krokstad, Sidsel', 'Moe, Nina', 'Nordbø, Svein Arne']",Emerg Infect Dis,,,True
3770ac55babf2fd6c2efdc3e58c8936a99b7a272,PMC,Dynamics of translation by single ribosomes through mRNA secondary structures,http://dx.doi.org/10.1038/nsmb.2544,PMC3648610,23542154,NO-CC CODE,"During protein synthesis, the ribosome translates nucleotide triplets in single-stranded mRNA into polypeptide sequences. Strong downstream mRNA secondary (2°) structures, which must be unfolded for translation, can slow or even halt protein synthesis. Here we employ single molecule fluorescence resonance energy transfer to determine reaction rates for specific steps within the elongation cycle as the Escherichia coli ribosome encounters stem loop or pseudoknot mRNA 2° structures. Downstream stem-loops containing 100% G-C base pairs decrease the rates of both tRNA translocation within the ribosome and deacylated tRNA dissociation from the ribosomal exit (E) site. Downstream stem-loops or pseudoknots containing both G-C and A-U pairs also decrease the rate of tRNA dissociation, but they have little effect on tRNA translocation rate. Thus, somewhat surprisingly, unfolding of mRNA 2° structures is more closely coupled to E-site tRNA dissociation than to tRNA translocation.",2013 May 31,"['Chen, Chunlai', 'Zhang, Haibo', 'Broitman, Steven L.', 'Reiche, Michael', 'Farrell, Ian', 'Cooperman, Barry S.', 'Goldman, Yale E.']",Nat Struct Mol Biol,,,True
490c64195eec44f9280570aece9732e7a120bd34,PMC,Dynamics of translation by single ribosomes through mRNA secondary structures,http://dx.doi.org/10.1038/nsmb.2544,PMC3648610,23542154,NO-CC CODE,"During protein synthesis, the ribosome translates nucleotide triplets in single-stranded mRNA into polypeptide sequences. Strong downstream mRNA secondary (2°) structures, which must be unfolded for translation, can slow or even halt protein synthesis. Here we employ single molecule fluorescence resonance energy transfer to determine reaction rates for specific steps within the elongation cycle as the Escherichia coli ribosome encounters stem loop or pseudoknot mRNA 2° structures. Downstream stem-loops containing 100% G-C base pairs decrease the rates of both tRNA translocation within the ribosome and deacylated tRNA dissociation from the ribosomal exit (E) site. Downstream stem-loops or pseudoknots containing both G-C and A-U pairs also decrease the rate of tRNA dissociation, but they have little effect on tRNA translocation rate. Thus, somewhat surprisingly, unfolding of mRNA 2° structures is more closely coupled to E-site tRNA dissociation than to tRNA translocation.",2013 May 31,"['Chen, Chunlai', 'Zhang, Haibo', 'Broitman, Steven L.', 'Reiche, Michael', 'Farrell, Ian', 'Cooperman, Barry S.', 'Goldman, Yale E.']",Nat Struct Mol Biol,,,True
8fac3cde7ec21f88cdaf5a5f6526f12e0353bfdb,PMC,IFITM3 restricts the morbidity and mortality associated with influenza,http://dx.doi.org/10.1038/nature10921,PMC3648786,22446628,NO-CC CODE,,2012 Mar 25,"['Everitt, Aaron R.', 'Clare, Simon', 'Pertel, Thomas', 'John, Sinu P.', 'Wash, Rachael S.', 'Smith, Sarah E.', 'Chin, Christopher R.', 'Feeley, Eric M.', 'Sims, Jennifer S.', 'Adams, David J.', 'Wise, Helen M.', 'Kane, Leanne', 'Goulding, David A.', 'Digard, Paul', 'Anttila, Verneri', 'Baillie, J. Kenneth', 'Walsh, Tim S.', 'Hume, David A.', 'Palotie, Aarno', 'Xue, Yali', 'Colonna, Vincenza', 'Tyler-Smith, Chris', 'Dunning, Jake', 'Gordon, Stephen B.', None, None, 'Smyth, Rosalind L.', 'Openshaw, Peter', 'Dougan, Gordon', 'Brass, Abraham L.', 'Kellam, Paul']",Nature,,,True
4f951fbc8db79c352bb152ff6194819523b32c18,PMC,IFITM3 restricts the morbidity and mortality associated with influenza,http://dx.doi.org/10.1038/nature10921,PMC3648786,22446628,NO-CC CODE,,2012 Mar 25,"['Everitt, Aaron R.', 'Clare, Simon', 'Pertel, Thomas', 'John, Sinu P.', 'Wash, Rachael S.', 'Smith, Sarah E.', 'Chin, Christopher R.', 'Feeley, Eric M.', 'Sims, Jennifer S.', 'Adams, David J.', 'Wise, Helen M.', 'Kane, Leanne', 'Goulding, David A.', 'Digard, Paul', 'Anttila, Verneri', 'Baillie, J. Kenneth', 'Walsh, Tim S.', 'Hume, David A.', 'Palotie, Aarno', 'Xue, Yali', 'Colonna, Vincenza', 'Tyler-Smith, Chris', 'Dunning, Jake', 'Gordon, Stephen B.', None, None, 'Smyth, Rosalind L.', 'Openshaw, Peter', 'Dougan, Gordon', 'Brass, Abraham L.', 'Kellam, Paul']",Nature,,,False
e25a627093e802ba8b7b53987ebae5366e98ea63,PMC,IFITM3 restricts the morbidity and mortality associated with influenza,http://dx.doi.org/10.1038/nature10921,PMC3648786,22446628,NO-CC CODE,,2012 Mar 25,"['Everitt, Aaron R.', 'Clare, Simon', 'Pertel, Thomas', 'John, Sinu P.', 'Wash, Rachael S.', 'Smith, Sarah E.', 'Chin, Christopher R.', 'Feeley, Eric M.', 'Sims, Jennifer S.', 'Adams, David J.', 'Wise, Helen M.', 'Kane, Leanne', 'Goulding, David A.', 'Digard, Paul', 'Anttila, Verneri', 'Baillie, J. Kenneth', 'Walsh, Tim S.', 'Hume, David A.', 'Palotie, Aarno', 'Xue, Yali', 'Colonna, Vincenza', 'Tyler-Smith, Chris', 'Dunning, Jake', 'Gordon, Stephen B.', None, None, 'Smyth, Rosalind L.', 'Openshaw, Peter', 'Dougan, Gordon', 'Brass, Abraham L.', 'Kellam, Paul']",Nature,,,False
f9a4350a22b0ac2d527dbbea0b0d4ebde180e2bf,PMC,Sequence and phylogenetic analysis of nucleocapsid genes of porcine epidemic diarrhea virus (PEDV) strains in China,http://dx.doi.org/10.1007/s00705-012-1592-4,PMC3668129,23389550,NO-CC CODE,"Porcine epidemic diarrhea virus (PEDV) causes acute diarrhea and dehydration with high mortality rates in swine. It has become increasingly problematic in China. Since the nucleocapsid (N) protein is highly conserved, it is a candidate protein for early diagnosis and vaccine development. In this study, the N genes of 15 PEDV strains were amplified by RT-PCR and cloned into the pMT-19T vector, sequenced, and compared to each other as well as to PEDV reference strains. The nucleotide sequences of the N gene of the Chinese PEDV strains consist of 1326 nucleotides and encode a 441-aa-long peptide. The nucleotide sequences of the fifteen PEDV strains in our study were 96.1-100 % identical to each other, and the deduced amino acid sequences were 94.8-100 % identical. Sequence comparison with other PEDV strains selected from GenBank revealed that their nucleotide sequences were 94.2-99.7 % identical to those of the Chinese PEDV strains, and their deduced amino acid sequences were 94.1-99.5 % identical. In addition, the fifteen strains showed a high degree of nucleotide sequence identity to the early domestic strains (98.4-99.7 %) except the LZC strain, but less sequence identity to the vaccine strain (CV777) used in China (94.7-97.7 %). Phylogenetic analysis showed that the Chinese PEDV strains are composed of a separate cluster including three early domestic strains (JS-2004-02, LJB/03 and DX) but differ genetically from the vaccine strain (CV777) and the early Korean strains (Chinju99 and SM98).",2013 Jun 7,"['Li, Zhili', 'Chen, Feng', 'Yuan, Yao', 'Zeng, Xiduo', 'Wei, Zhongyan', 'Zhu, Ling', 'Sun, Baoli', 'Xie, Qingmei', 'Cao, Yongchang', 'Xue, Chunyi', 'Ma, Jingyun', 'Bee, Yingzuo']",Arch Virol,,,True
4b7bfd89ad2142ae4d193ed7925dc02889e31c27,PMC,Design of a set of probes with high potential for influenza virus epidemiological surveillance,http://dx.doi.org/10.6026/97320630009414,PMC3670124,23750091,NO-CC CODE,"An Influenza Probe Set (IPS) consisting in 1,249 9-mer probes for genomic fingerprinting of closely and distantly related Influenza Virus strains was designed and tested in silico. The IPS was derived from alignments of Influenza genomes. The RNA segments of 5,133 influenza strains having diverse degree of relatedness were concatenated and aligned. After alignment, 9-mer sites having high Shannon entropy were searched. Additional criteria such as: G+C content between 35 to 65%, absence of dimer or trimer consecutive repeats, a minimum of 2 differences between 9mers and selecting only sequences with Tm values between 34.5 and 36.5oC were applied for selecting probes with high sequential entropy. Virtual Hybridization was used to predict Genomic Fingerprints to assess the capability of the IPS to discriminate between influenza and related strains. Distance scores between pairs of Influenza Genomic Fingerprints were calculated, and used for estimating Taxonomic Trees. Visual examination of both Genomic Fingerprints and Taxonomic Trees suggest that the IPS is able to discriminate between distant and closely related Influenza strains. It is proposed that the IPS can be used to investigate, by virtual or experimental hybridization, any new, and potentially virulent, strain.",2013 Apr 30,"['Carreño-Durán, Luis R', 'Larios-Serrato, V', 'Jaimes-Díaz, Hueman', 'Pérez-Cervantes, Hilda', 'Zepeda-López, Héctor', 'Sánchez-Vallejo, Carlos Javier', 'Olguín-Ruiz, Gabriela Edith', 'Maldonado-Rodríguez, Rogelio', 'Méndez-Tenorio, Alfonso']",Bioinformation,,,True
42f18bf9a496b45c78d72ea080d2e8c885c41187,PMC,Design of a set of probes with high potential for influenza virus epidemiological surveillance,http://dx.doi.org/10.6026/97320630009414,PMC3670124,23750091,NO-CC CODE,"An Influenza Probe Set (IPS) consisting in 1,249 9-mer probes for genomic fingerprinting of closely and distantly related Influenza Virus strains was designed and tested in silico. The IPS was derived from alignments of Influenza genomes. The RNA segments of 5,133 influenza strains having diverse degree of relatedness were concatenated and aligned. After alignment, 9-mer sites having high Shannon entropy were searched. Additional criteria such as: G+C content between 35 to 65%, absence of dimer or trimer consecutive repeats, a minimum of 2 differences between 9mers and selecting only sequences with Tm values between 34.5 and 36.5oC were applied for selecting probes with high sequential entropy. Virtual Hybridization was used to predict Genomic Fingerprints to assess the capability of the IPS to discriminate between influenza and related strains. Distance scores between pairs of Influenza Genomic Fingerprints were calculated, and used for estimating Taxonomic Trees. Visual examination of both Genomic Fingerprints and Taxonomic Trees suggest that the IPS is able to discriminate between distant and closely related Influenza strains. It is proposed that the IPS can be used to investigate, by virtual or experimental hybridization, any new, and potentially virulent, strain.",2013 Apr 30,"['Carreño-Durán, Luis R', 'Larios-Serrato, V', 'Jaimes-Díaz, Hueman', 'Pérez-Cervantes, Hilda', 'Zepeda-López, Héctor', 'Sánchez-Vallejo, Carlos Javier', 'Olguín-Ruiz, Gabriela Edith', 'Maldonado-Rodríguez, Rogelio', 'Méndez-Tenorio, Alfonso']",Bioinformation,,,False
c09a10b1d2e8dedabdc06617cff5c3d86b111d18,PMC,Electrochemical Sensors for Clinic Analysis,,PMC3673406,27879810,NO-CC CODE,"Demanded by modern medical diagnosis, advances in microfabrication technology have led to the development of fast, sensitive and selective electrochemical sensors for clinic analysis. This review addresses the principles behind electrochemical sensor design and fabrication, and introduces recent progress in the application of electrochemical sensors to analysis of clinical chemicals such as blood gases, electrolytes, metabolites, DNA and antibodies, including basic and applied research. Miniaturized commercial electrochemical biosensors will form the basis of inexpensive and easy to use devices for acquiring chemical information to bring sophisticated analytical capabilities to the non-specialist and general public alike in the future.",2008 Mar 27,"['Wang, You', 'Xu, Hui', 'Zhang, Jianming', 'Li, Guang']",Sensors (Basel),,,True
fe96465c506e69345e10773221f72b871b4e742f,PMC,Novel compounds for the treatment of Duchenne muscular dystrophy: emerging therapeutic agents,http://dx.doi.org/10.2147/TACG.S8762,PMC3681176,23776365,NO-CC CODE,"The identification of dystrophin and the causative role of mutations in this gene in Duchenne and Becker muscular dystrophies (D/BMD) was expected to lead to timely development of effective therapies. Despite over 20 years of research, corticosteroids remain the only available pharmacological treatment for DMD, although significant benefits and extended life have resulted from advances in the clinical care and management of DMD individuals. Effective treatment of DMD will require dystrophin restitution in skeletal, cardiac, and smooth muscles and nonmuscle tissues; however, modulation of muscle loss and regeneration has the potential to play an important role in altering the natural history of DMD, particularly in combination with other treatments. Emerging biological, molecular, and small molecule therapeutics are showing promise in ameliorating this devastating disease, and it is anticipated that regulatory environments will need to display some flexibility in order to accommodate the new treatment paradigms.",2011 Mar 10,"['Wilton, Steve D', 'Fletcher, Sue']",Appl Clin Genet,,,True
bd42860179bf3032b5da35bf4cba948603f8dc10,PMC,The epidemiological and public health research response to 2009 pandemic influenza A(H1N1): experiences from Hong Kong,http://dx.doi.org/10.1111/j.1750-2659.2012.00420.x,PMC3705741,22883352,NO-CC CODE,"In recent years, Hong Kong has invested in research infrastructure to appropriately respond to novel infectious disease epidemics. Research from Hong Kong made a strong contribution to the international response to the 2009 influenza A (H1N1) pandemic (pH1N1). Summarizing, describing, and reviewing Hong Kong’s response to the 2009 pandemic, this article aimed to identify key elements of a real‐time research response. A systematic search in PubMed and EMBASE for research into the infection dynamics and natural history, impact, or control of pH1N1 in Hong Kong. Eligible articles were analyzed according to their scope. Fifty‐five articles were included in the review. Transmissibility of pH1N1 was similar in Hong Kong to elsewhere, and only a small fraction of infections were associated with severe disease. School closures were effective in reducing pH1N1 transmission, oseltamivir was effective for treatment of severe cases while convalescent plasma therapy has the potential to mitigate future pandemics. There was a rapid and comprehensive research response to pH1N1 in Hong Kong, providing important information on the epidemiology of the novel virus with relevance internationally as well as locally. The scientific knowledge gained through these detailed studies of pH1N1 is now being used to revise and update pandemic plans. The experiences of the research response in Hong Kong could provide a template for the research response to future emerging and reemerging disease epidemics.",2013 May 9,"['Wu, Peng', 'Cowling, Benjamin J.', 'Wu, Joseph T.', 'Lau, Eric H. Y.', 'Ip, Dennis K. M.', 'Nishiura, Hiroshi']",Influenza Other Respir Viruses,,,True
a334bbb2a7fe8f65dccde53a8d0234d524bf10f7,PMC,Genomics and outbreak investigation: from sequence to consequence,http://dx.doi.org/10.1186/gm440,PMC3706975,23673226,NO-CC CODE,"Outbreaks of infection can be devastating for individuals and societies. In this review, we examine the applications of new high-throughput sequencing approaches to the identification and characterization of outbreaks, focusing on the application of whole-genome sequencing (WGS) to outbreaks of bacterial infection. We describe traditional epidemiological analysis and show how WGS can be informative at multiple steps in outbreak investigation, as evidenced by many recent studies. We conclude that high-throughput sequencing approaches can make a significant contribution to the investigation of outbreaks of bacterial infection and that the integration of WGS with epidemiological investigation, diagnostic assays and antimicrobial susceptibility testing will precipitate radical changes in clinical microbiology and infectious disease epidemiology in the near future. However, several challenges remain before WGS can be routinely used in outbreak investigation and clinical practice.",2013 Apr 29,"['Robinson, Esther R', 'Walker, Timothy M', 'Pallen, Mark J']",Genome Med,,,True
16692bb9b2915fbac5398b1171076aeeb4397528,PMC,Public Health Lessons from Severe Acute Respiratory Syndrome a Decade Later,http://dx.doi.org/10.3201/eid1906.121426,PMC3713823,23739634,NO-CC CODE,"The outbreak of severe acute respiratory syndrome in 2002–2003 exacted considerable human and economic costs from countries involved. It also exposed major weaknesses in several of these countries in coping with an outbreak of a newly emerged infectious disease. In the 10 years since the outbreak, in addition to the increase in knowledge of the biology and epidemiology of this disease, a major lesson learned is the value of having a national public health institute that is prepared to control disease outbreaks and designed to coordinate a national response and assist localities in their responses.",2013 Jun,"['Koplan, Jeffrey P.', 'Butler-Jones, David', 'Tsang, Thomas', 'Yu, Wang']",Emerg Infect Dis,,,True
ff304104b0e2e1f4c8318ec119a79721fe7a4467,PMC,"Pandemic Influenza Planning, United States, 1978–2008",http://dx.doi.org/10.3201/eid1906.121478,PMC3713824,23731839,NO-CC CODE,"During the past century, 4 influenza pandemics occurred. After the emergence of a novel influenza virus of swine origin in 1976, national, state, and local US public health authorities began planning efforts to respond to future pandemics. Several events have since stimulated progress in public health emergency planning: the 1997 avian influenza A(H5N1) outbreak in Hong Kong, China; the 2001 anthrax attacks in the United States; the 2003 outbreak of severe acute respiratory syndrome; and the 2003 reemergence of influenza A(H5N1) virus infection in humans. We outline the evolution of US pandemic planning since the late 1970s, summarize planning accomplishments, and explain their ongoing importance. The public health community’s response to the 2009 influenza A(H1N1)pdm09 pandemic demonstrated the value of planning and provided insights into improving future plans and response efforts. Preparedness planning will enhance the collective, multilevel response to future public health crises.",2013 Jun,"['Iskander, John', 'Strikas, Raymond A.', 'Gensheimer, Kathleen F.', 'Cox, Nancy J.', 'Redd, Stephen C.']",Emerg Infect Dis,,,True
b0b8ac292312c6642c37e502d2fd803955084c17,PMC,"Active Surveillance for Influenza A Virus among Swine, Midwestern United States, 2009–2011",http://dx.doi.org/10.3201/eid1906.121637,PMC3713829,23735740,NO-CC CODE,"Veterinary diagnostic laboratories identify and characterize influenza A viruses primarily through passive surveillance. However, additional surveillance programs are needed. To meet this need, an active surveillance program was conducted at pig farms throughout the midwestern United States. From June 2009 through December 2011, nasal swab samples were collected monthly from among 540 groups of growing pigs and tested for influenza A virus by real-time reverse transcription PCR. Of 16,170 samples, 746 were positive for influenza A virus; of these, 18.0% were subtype H1N1, 16.0% H1N2, 7.6% H3N2, and 14.5% (H1N1)pdm09. An influenza (H3N2) and (H1N1)pdm09 virus were identified simultaneously in 8 groups. This active influenza A virus surveillance program provided quality data and increased the understanding of the current situation of circulating viruses in the midwestern US pig population.",2013 Jun,"['Corzo, Cesar A.', 'Culhane, Marie', 'Juleen, Kevin', 'Stigger-Rosser, Evelyn', 'Ducatez, Mariette F.', 'Webby, Richard J.', 'Lowe, James F.']",Emerg Infect Dis,,,True
00683d59d56123ae85e080d00ef1b3edd3f7405d,PMC,Transmission Potential of Rift Valley Fever Virus over the Course of the 2010 Epidemic in South Africa,http://dx.doi.org/10.3201/eid1906.121641,PMC3713830,23735606,NO-CC CODE,"A Rift Valley fever (RVF) epidemic affecting animals on domestic livestock farms was reported in South Africa during January–August 2010. The first cases occurred after heavy rainfall, and the virus subsequently spread countrywide. To determine the possible effect of environmental conditions and vaccination on RVF virus transmissibility, we estimated the effective reproduction number (R(e)) for the virus over the course of the epidemic by extending the Wallinga and Teunis algorithm with spatial information. R(e) reached its highest value in mid-February and fell below unity around mid-March, when vaccination coverage was 7.5%–45.7% and vector-suitable environmental conditions were maintained. The epidemic fade-out likely resulted first from the immunization of animals following natural infection or vaccination. The decline in vector-suitable environmental conditions from April onwards and further vaccination helped maintain R(e) below unity. Increased availability of vaccine use data would enable evaluation of the effect of RVF vaccination campaigns.",2013 Jun,"['Métras, Raphaëlle', 'Baguelin, Marc', 'Edmunds, W. John', 'Thompson, Peter N.', 'Kemp, Alan', 'Pfeiffer, Dirk U.', 'Collins, Lisa M.', 'White, Richard G.']",Emerg Infect Dis,,,True
ca3eeb26589ebc7faeeec6943a4340583d6a467f,PMC,Transmission Potential of Rift Valley Fever Virus over the Course of the 2010 Epidemic in South Africa,http://dx.doi.org/10.3201/eid1906.121641,PMC3713830,23735606,NO-CC CODE,"A Rift Valley fever (RVF) epidemic affecting animals on domestic livestock farms was reported in South Africa during January–August 2010. The first cases occurred after heavy rainfall, and the virus subsequently spread countrywide. To determine the possible effect of environmental conditions and vaccination on RVF virus transmissibility, we estimated the effective reproduction number (R(e)) for the virus over the course of the epidemic by extending the Wallinga and Teunis algorithm with spatial information. R(e) reached its highest value in mid-February and fell below unity around mid-March, when vaccination coverage was 7.5%–45.7% and vector-suitable environmental conditions were maintained. The epidemic fade-out likely resulted first from the immunization of animals following natural infection or vaccination. The decline in vector-suitable environmental conditions from April onwards and further vaccination helped maintain R(e) below unity. Increased availability of vaccine use data would enable evaluation of the effect of RVF vaccination campaigns.",2013 Jun,"['Métras, Raphaëlle', 'Baguelin, Marc', 'Edmunds, W. John', 'Thompson, Peter N.', 'Kemp, Alan', 'Pfeiffer, Dirk U.', 'Collins, Lisa M.', 'White, Richard G.']",Emerg Infect Dis,,,True
394a138dbcb0699e087ecd3747fa370c69565909,PMC,"Novel SARS-like Betacoronaviruses in Bats, China, 2011",http://dx.doi.org/10.3201/eid1906.121648,PMC3713832,23739658,NO-CC CODE,"To clarify the evolutionary relationships among betavoronaviruses that infect bats, we analyzed samples collected during 2010–2011 from 14 insectivorous bat species in China. We identified complete genomes of 2 novel betacoronaviruses in Rhinolophus pusillus and Chaerephon plicata bats, which showed close genetic relationships with severe acute respiratory syndrome coronaviruses.",2013 Jun,"['Yang, Li', 'Wu, Zhiqiang', 'Ren, Xianwen', 'Yang, Fan', 'He, Guimei', 'Zhang, Junpeng', 'Dong, Jie', 'Sun, Lilian', 'Zhu, Yafang', 'Du, Jiang', 'Zhang, Shuyi', 'Jin, Qi']",Emerg Infect Dis,,,True
acc553c568c83d482c22c85f280ea92a5afccdab,PMC,"Novel Poxvirus in Big Brown Bats, Northwestern United States",http://dx.doi.org/10.3201/eid1906.121713,PMC3713833,23735421,NO-CC CODE,A wildlife hospital and rehabilitation center in northwestern United States received several big brown bats with necrosuppurative osteomyelitis in multiple joints. Wing and joint tissues were positive by PCR for poxvirus. Thin-section electron microscopy showed poxvirus particles within A-type inclusions. Phylogenetic comparison supports establishment of a new genus of Poxviridae.,2013 Jun,"['Emerson, Ginny L.', 'Nordhausen, Robert', 'Garner, Michael M.', 'Huckabee, John R.', 'Johnson, Steven', 'Wohrle, Ron D.', 'Davidson, Whitni B.', 'Wilkins, Kimberly', 'Li, Yu', 'Doty, Jeffrey B.', 'Gallardo-Romero, Nadia F.', 'Metcalfe, Maureen G.', 'Karem, Kevin L.', 'Damon, Inger K.', 'Carroll, Darin S.']",Emerg Infect Dis,,,True
41f28afec098e61c475678ac2c8546f640c8b284,PMC,Prospects for Emerging Infections in East and Southeast Asia 10 Years after Severe Acute Respiratory Syndrome,http://dx.doi.org/10.3201/eid1906.121783,PMC3713834,23738977,NO-CC CODE,"It is 10 years since severe acute respiratory syndrome (SARS) emerged, and East and Southeast Asia retain a reputation as a hot spot of emerging infectious diseases. The region is certainly a hot spot of socioeconomic and environmental change, and although some changes (e.g., urbanization and agricultural intensification) may reduce the probability of emerging infectious diseases, the effect of any individual emergence event may be increased by the greater concentration and connectivity of livestock, persons, and products. The region is now better able to detect and respond to emerging infectious diseases than it was a decade ago, but the tools and methods to produce sufficiently refined assessments of the risks of disease emergence are still lacking. Given the continued scale and pace of change in East and Southeast Asia, it is vital that capabilities for predicting, identifying, and controlling biologic threats do not stagnate as the memory of SARS fades.",2013 Jun,"['Horby, Peter W,', 'Pfeiffer, Dirk', 'Oshitani, Hitoshi']",Emerg Infect Dis,,,True
6f22bd9b49b8d4e320160285611adac4cdbe9e1a,PMC,Cell Culture and Electron Microscopy for Identifying Viruses in Diseases of Unknown Cause,http://dx.doi.org/10.3201/eid1906.130173,PMC3713842,23731788,NO-CC CODE,"During outbreaks of infectious diseases or in cases of severely ill patients, it is imperative to identify the causative agent. This report describes several events in which virus isolation and identification by electron microscopy were critical to initial recognition of the etiologic agent, which was further analyzed by additional laboratory diagnostic assays. Examples include severe acute respiratory syndrome coronavirus, and Nipah, lymphocytic choriomeningitis, West Nile, Cache Valley, and Heartland viruses. These cases illustrate the importance of the techniques of cell culture and electron microscopy in pathogen identification and recognition of emerging diseases.",2013 Jun,"['Goldsmith, Cynthia S.', 'Ksiazek, Thomas G.', 'Rollin, Pierre E.', 'Comer, James A.', 'Nicholson, William L.', 'Peret, Teresa C.T.', 'Erdman, Dean D.', 'Bellini, William J.', 'Harcourt, Brian H.', 'Rota, Paul A.', 'Bhatnagar, Julu', 'Bowen, Michael D.', 'Erickson, Bobbie R.', 'McMullan, Laura K.', 'Nichol, Stuart T.', 'Shieh, Wun-Ju', 'Paddock, Christopher D.', 'Zaki, Sherif R.']",Emerg Infect Dis,,,True
404ca779551d8f2defd48fa692a4ae44bb729e15,PMC,Progress in Global Surveillance and Response Capacity 10 Years after Severe Acute Respiratory Syndrome,http://dx.doi.org/10.3201/eid1906.130192,PMC3713843,23731871,NO-CC CODE,"Ten years have elapsed since the World Health Organization issued its first global alert for an unexplained illness named severe acute respiratory syndrome (SARS). The anniversary provides an opportunity to reflect on the international response to this new global microbial threat. While global surveillance and response capacity for public health threats have been strengthened, critical gaps remain. Of 194 World Health Organization member states that signed on to the International Health Regulations (2005), <20% had achieved compliance with the core capacities required by the deadline in June 2012. Lessons learned from the global SARS outbreak highlight the need to avoid complacency, strengthen efforts to improve global capacity to address the next pandemic using all available 21st century tools, and support research to develop new treatment options, countermeasures, and insights while striving to address the global inequities that are the root cause of many of these challenges.",2013 Jun,"['Braden, Christopher R.', 'Dowell, Scott F.', 'Jernigan, Daniel B.', 'Hughes, James M.']",Emerg Infect Dis,,,True
46365f6b8a2f8ebbfea7feab338c0df7a96842dc,PMC,Mutation in Spike Protein Cleavage Site and Pathogenesis of Feline Coronavirus,http://dx.doi.org/10.3201/eid1907.121094,PMC3713968,23763835,NO-CC CODE,"Feline coronaviruses (FCoV) exist as 2 biotypes: feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). FECV causes subclinical infections; FIPV causes feline infectious peritonitis (FIP), a systemic and fatal disease. It is thought that mutations in FECV enable infection of macrophages, causing FIP. However, the molecular basis for this biotype switch is unknown. We examined a furin cleavage site in the region between receptor-binding (S1) and fusion (S2) domains of the spike of serotype 1 FCoV. FECV sequences were compared with FIPV sequences. All FECVs had a conserved furin cleavage motif. For FIPV, there was a correlation with the disease and >1 substitution in the S1/S2 motif. Fluorogenic peptide assays confirmed that the substitutions modulate furin cleavage. We document a functionally relevant S1/S2 mutation that arises when FIP develops in a cat. These insights into FIP pathogenesis may be useful in development of diagnostic, prevention, and treatment measures against coronaviruses.",2013 Jul,"['Licitra, Beth N.', 'Millet, Jean K.', 'Regan, Andrew D.', 'Hamilton, Brian S.', 'Rinaldi, Vera D.', 'Duhamel, Gerald E.', 'Whittaker, Gary R.']",Emerg Infect Dis,,,True
dcea6ce0132c84a8483fb8999554184d374941af,PMC,Mutation in Spike Protein Cleavage Site and Pathogenesis of Feline Coronavirus,http://dx.doi.org/10.3201/eid1907.121094,PMC3713968,23763835,NO-CC CODE,"Feline coronaviruses (FCoV) exist as 2 biotypes: feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). FECV causes subclinical infections; FIPV causes feline infectious peritonitis (FIP), a systemic and fatal disease. It is thought that mutations in FECV enable infection of macrophages, causing FIP. However, the molecular basis for this biotype switch is unknown. We examined a furin cleavage site in the region between receptor-binding (S1) and fusion (S2) domains of the spike of serotype 1 FCoV. FECV sequences were compared with FIPV sequences. All FECVs had a conserved furin cleavage motif. For FIPV, there was a correlation with the disease and >1 substitution in the S1/S2 motif. Fluorogenic peptide assays confirmed that the substitutions modulate furin cleavage. We document a functionally relevant S1/S2 mutation that arises when FIP develops in a cat. These insights into FIP pathogenesis may be useful in development of diagnostic, prevention, and treatment measures against coronaviruses.",2013 Jul,"['Licitra, Beth N.', 'Millet, Jean K.', 'Regan, Andrew D.', 'Hamilton, Brian S.', 'Rinaldi, Vera D.', 'Duhamel, Gerald E.', 'Whittaker, Gary R.']",Emerg Infect Dis,,,False
6c72317009dd3ab6117004c7121c1cca52cbdbf6,PMC,Steps to a Sustainable Public Health Surveillance Enterprise
A Commentary from the International Society for Disease Surveillance,http://dx.doi.org/10.5210/ojphi.v5i2.4703,PMC3733763,23923095,NO-CC CODE,"More than a decade into the 21(st) century, the ability to effectively monitor community health status, as well as forecast, detect, and respond to disease outbreaks and other events of public health significance, remains a major challenge. As an issue that affects population health, economic stability, and global security, the public health surveillance enterprise warrants the attention of decision makers at all levels. Public health practitioners responsible for surveillance functions are best positioned to identify the key elements needed for creating and maintaining effective and sustainable surveillance systems. This paper presents the recommendations of the Sustainable Surveillance Workgroup convened by the International Society for Disease Surveillance (ISDS) to identify strategies for building, strengthening, and maintaining surveillance systems that are equipped to provide data continuity and to handle both established and new data sources and public health surveillance practices.",2013 Jul 1,"['Mirza, Nabila', 'Reynolds, Tera', 'Coletta, Michael', 'Suda, Katie', 'Soyiri, Ireneous', 'Markle, Ariana', 'Leopold, Henry', 'Lenert, Leslie', 'Samoff, Erika', 'Siniscalchi, Alan', 'Streichert, Laura']",Online J Public Health Inform,,,True
1bb5464402133a23adce74998e5658cf9f3fa491,PMC,Comparing Neural-Network Scoring Functions and the State of the Art: Applications to Common Library Screening,http://dx.doi.org/10.1021/ci400042y,PMC3735370,23734946,NO-CC CODE,"[Image: see text] We compare established docking programs, AutoDock Vina and Schrödinger’s Glide, to the recently published NNScore scoring functions. As expected, the best protocol to use in a virtual-screening project is highly dependent on the target receptor being studied. However, the mean screening performance obtained when candidate ligands are docked with Vina and rescored with NNScore 1.0 is not statistically different than the mean performance obtained when docking and scoring with Glide. We further demonstrate that the Vina and NNScore docking scores both correlate with chemical properties like small-molecule size and polarizability. Compensating for these potential biases leads to improvements in virtual screen performance. Composite NNScore-based scoring functions suited to a specific receptor further improve performance. We are hopeful that the current study will prove useful for those interested in computer-aided drug design.",2013 Jul 22,"['Durrant, Jacob D.', 'Friedman, Aaron\nJ.', 'Rogers, Kathleen\nE.', 'McCammon, J. Andrew']",J Chem Inf Model,,,True
88356a43079eda96b1416bb12b8eca07a73d4f02,PMC,Comparing Neural-Network Scoring Functions and the State of the Art: Applications to Common Library Screening,http://dx.doi.org/10.1021/ci400042y,PMC3735370,23734946,NO-CC CODE,"[Image: see text] We compare established docking programs, AutoDock Vina and Schrödinger’s Glide, to the recently published NNScore scoring functions. As expected, the best protocol to use in a virtual-screening project is highly dependent on the target receptor being studied. However, the mean screening performance obtained when candidate ligands are docked with Vina and rescored with NNScore 1.0 is not statistically different than the mean performance obtained when docking and scoring with Glide. We further demonstrate that the Vina and NNScore docking scores both correlate with chemical properties like small-molecule size and polarizability. Compensating for these potential biases leads to improvements in virtual screen performance. Composite NNScore-based scoring functions suited to a specific receptor further improve performance. We are hopeful that the current study will prove useful for those interested in computer-aided drug design.",2013 Jul 22,"['Durrant, Jacob D.', 'Friedman, Aaron\nJ.', 'Rogers, Kathleen\nE.', 'McCammon, J. Andrew']",J Chem Inf Model,,,False
3ed8570c9e422b49c3583e04543e636a4154777b,PMC,"Primary and Secondary Human Bocavirus 1 Infections in a Family, Finland",http://dx.doi.org/10.3201/eid.1908.130074,PMC3739498,23876382,NO-CC CODE,"Human bocavirus 1 (HBoV1) was detected in a young child hospitalized for pneumonia and subsequently in his twin brother and other family members. The mother’s nasopharyngeal samples intermittently showed HBoV1 DNA; the grandmother had HBoV1 reinfection. Findings in this family lead to consideration of HBoV virulence, latency, and reactivation.",2013 Aug,"['Jula, Alma', 'Waris, Matti', 'Kantola, Kalle', 'Peltola, Ville', 'Söderlund-Venermo, Maria', 'Hedman, Klaus', 'Ruuskanen, Olli']",Emerg Infect Dis,,,True
51792eea98bf36177fc815a79e8bd713c986d393,PMC,The New Global Health,http://dx.doi.org/10.3201/eid1908.130121,PMC3739536,23876365,NO-CC CODE,"Global health reflects the realities of globalization, including worldwide dissemination of infectious and noninfectious public health risks. Global health architecture is complex and better coordination is needed between multiple organizations. Three overlapping themes determine global health action and prioritization: development, security, and public health. These themes play out against a background of demographic change, socioeconomic development, and urbanization. Infectious diseases remain critical factors, but are no longer the major cause of global illness and death. Traditional indicators of public health, such as maternal and infant mortality rates no longer describe the health status of whole societies; this change highlights the need for investment in vital registration and disease-specific reporting. Noncommunicable diseases, injuries, and mental health will require greater attention from the world in the future. The new global health requires broader engagement by health organizations and all countries for the objectives of health equity, access, and coverage as priorities beyond the Millennium Development Goals are set.",2013 Aug,"['De Cock, Kevin M.', 'Simone, Patricia M.', 'Davison, Veronica', 'Slutsker, Laurence']",Emerg Infect Dis,,,True
c96e2b9d86911b1bc2bc67cd49081b64065764c0,PMC,The New Global Health,http://dx.doi.org/10.3201/eid1908.130121,PMC3739536,23876365,NO-CC CODE,"Global health reflects the realities of globalization, including worldwide dissemination of infectious and noninfectious public health risks. Global health architecture is complex and better coordination is needed between multiple organizations. Three overlapping themes determine global health action and prioritization: development, security, and public health. These themes play out against a background of demographic change, socioeconomic development, and urbanization. Infectious diseases remain critical factors, but are no longer the major cause of global illness and death. Traditional indicators of public health, such as maternal and infant mortality rates no longer describe the health status of whole societies; this change highlights the need for investment in vital registration and disease-specific reporting. Noncommunicable diseases, injuries, and mental health will require greater attention from the world in the future. The new global health requires broader engagement by health organizations and all countries for the objectives of health equity, access, and coverage as priorities beyond the Millennium Development Goals are set.",2013 Aug,"['De Cock, Kevin M.', 'Simone, Patricia M.', 'Davison, Veronica', 'Slutsker, Laurence']",Emerg Infect Dis,,,True
c16fecd2784f334dbf3265085fa2fc4d20ea19ae,PMC,"Group C Betacoronavirus in Bat Guano Fertilizer, Thailand",http://dx.doi.org/10.3201/eid1908.130119,PMC3739538,23880503,NO-CC CODE,,2013 Aug,"['Wacharapluesadee, Supaporn', 'Sintunawa, Chirapol', 'Kaewpom, Thongchai', 'Khongnomnan, Kritsada', 'Olival, Kevin J.', 'Epstein, Jonathan H.', 'Rodpan, Apaporn', 'Sangsri, Paiboon', 'Intarut, Nirun', 'Chindamporn, Ariya', 'Suksawa, Kanyarat', 'Hemachudha, Thiravat']",Emerg Infect Dis,,,True
568fec0df53acc098777e861ab6b824bf22ca3e4,PMC,Altered distribution of mucosal NK cells during HIV infection,http://dx.doi.org/10.1038/mi.2011.40,PMC3740353,21993602,NO-CC CODE,"The human gut mucosa is a major site of HIV infection and infection-associated pathogenesis. Increasing evidence shows that natural killer (NK) cells play an important role in control of HIV infection but the mechanism(s) by which they mediate antiviral activity in the gut is unclear. Here we show two distinct subsets of NK cells exist in the gut, one localized to intraepithelial spaces (IEL) and the other to the lamina propria (LP). The frequency of both subsets of NK cells was reduced in chronic infection, whereas IEL NK cells remained stable in spontaneous controllers with protective KIR/HLA genotypes. Both IEL and LP NK cells were significantly expanded in immunologic non-responsive (INR) patients, who incompletely recovered CD4+ T cells on HAART. These data suggest that both IEL and LP NK cells may expand in the gut in an effort to compensate for compromised CD4+ T cell recovery, but that only IEL NK cells may be involved in providing durable control of HIV in the gut,",2012 Jan 12,"['Sips, Magdalena', 'Sciaranghella, Gaia', 'Diefenbach, Thomas', 'Dugast, Anne-Sophie', 'Berger, Christoph T.', 'Liu, Qingquan', 'Kwon, Douglas', 'Ghebremichael, Musie', 'Estes, Jacob D.', 'Carrington, Mary', 'Martin, Jeffrey N.', 'Deeks, Steven G.', 'Hunt, Peter W.', 'Alter, Galit']",Mucosal Immunol,,,True
5c5a6ea2bb2e3865e47d4495eb6ee3e4cddb1134,PMC,A Prospective Evaluation of Real-Time PCR Assays for the Detection of Orientia tsutsugamushi and Rickettsia spp. for Early Diagnosis of Rickettsial Infections during the Acute Phase of Undifferentiated Febrile Illness,http://dx.doi.org/10.4269/ajtmh.12-0600,PMC3741253,23732256,NO-CC CODE,"One hundred and eighty febrile patients were analyzed in a prospective evaluation of Orientia tsutsugamushi and Rickettsia spp. real-time polymerase chain reaction (PCR) assays for early diagnosis of rickettsial infections. By paired serology, 3.9% (7 of 180) and 6.1% (11 of 180) of patients were confirmed to have acute scrub or murine typhus, respectively. The PCR assays for the detection of O. tsutsugamushi and Rickettsia spp. had high specificity (99.4% [95% confidence interval (CI): 96.8–100] and 100% [95% CI: 97.8–100], respectively). The PCR results were also compared with immunoglobulin M (IgM) immunofluorescence assay (IFA) on acute sera. For O. tsutsugamushi, PCR sensitivity was twice that of acute specimen IgM IFA (28.6% versus 14.3%; McNemar's P = 0.3). For Rickettsia spp., PCR was four times as sensitive as acute specimen IgM IFA (36.4% versus 9.1%; P = 0.08), although this was not statistically significant. Whole blood and buffy coat, but not serum, were acceptable specimens for these PCRs. Further evaluation of these assays in a larger prospective study is warranted.",2013 Aug 7,"['Watthanaworawit, Wanitda', 'Turner, Paul', 'Turner, Claudia', 'Tanganuchitcharnchai, Ampai', 'Richards, Allen L.', 'Bourzac, Kevin M.', 'Blacksell, Stuart D.', 'Nosten, François']",Am J Trop Med Hyg,,,True
123c9d8da7648c728ebc6bfcd0e3b57cdc9cc8b7,PMC,Autopsy in critical illness: is it obsolete?,,PMC374374,14624674,NO-CC CODE,"The autopsy continues to have important implications for patient management in critical illness. It is not obsolete. Autopsy data help us to track shifts in disease prevalence over time and to heighten surveillance for serious diagnoses that are commonly missed. These data help us to identify important contributors to death that may be remediated through quality assurance and control programs. In discrete patient subsets, information from autopsies may reinforce the degree of certainty surrounding end-of-life decision-making.",2003 Sep 26,"Herridge, Margaret S",Crit Care,,,True
2a92147a3684058e383a4b403c25cacbda28022b,PMC,SARS Resources,http://dx.doi.org/10.1186/cc2383,PMC374376,,NO-CC CODE,,2003 Sep 29,"Kraus, Peter A",Crit Care,,,False
c20b07555abfd0ee9bb51260bbbb997f30a95031,PMC,Communication in the Toronto critical care community: important lessons learned during SARS,,PMC374381,14624673,NO-CC CODE,"The SARS outbreak in 2003 pushed Toronto's health care system to its limits. Staffing shortages, transmission of SARS within the ICU, and the influx of critically ill SARS patients were some unique challenges to the delivery of critical care. Communication strategies were a key component in the critical care response to SARS. Regular teleconference calls, web-based training and education, and the rapid coordination of research studies were some of the initiatives developed within the Toronto critical care community during the SARS outbreak. Other critical care communities should consider their communication strategies in advance of similar events.",2003 Oct 10,"['Booth, Christopher M', 'Stewart, Thomas E']",Crit Care,,,True
ee46c9064c2ef4916ba7d54c80236d3cb1781635,PMC,Deubiquitylating Enzymes and DNA Damage Response Pathways,http://dx.doi.org/10.1007/s12013-013-9635-3,PMC3756857,23712866,NO-CC CODE,"Covalent post-translational modification of proteins by ubiquitin and ubiquitin-like factors has emerged as a general mechanism to regulate myriad intra-cellular processes. The addition and removal of ubiquitin or ubiquitin-like proteins from factors has recently been demonstrated as a key mechanism to modulate DNA damage response (DDR) pathways. It is thus, timely to evaluate the potential for ubiquitin pathway enzymes as DDR drug targets for therapeutic intervention. The synthetic lethal approach provides exciting opportunities for the development of targeted therapies to treat cancer: most tumours have lost critical DDR pathways, and thus rely more heavily on the remaining pathways, while normal tissues are still equipped with all DDR pathways. Here, we review key deubiquitylating enzymes (DUBs) involved in DDR pathways, and describe how targeting DUBs may lead to selective therapies to treat cancer patients.",2013 May 28,"['Jacq, Xavier', 'Kemp, Mark', 'Martin, Niall M. B.', 'Jackson, Stephen P.']",Cell Biochem Biophys,,,True
b85fb3c87b048a1ead4177bf01e987ed23f87c33,PMC,Cationic Host Defence Peptides: Potential as Antiviral Therapeutics,http://dx.doi.org/10.1007/s40259-013-0039-0,PMC3775153,23649937,NO-CC CODE,"There is a pressing need to develop new antiviral treatments; of the 60 drugs currently available, half are aimed at HIV-1 and the remainder target only a further six viruses. This demand has led to the emergence of possible peptide therapies, with 15 currently in clinical trials. Advancements in understanding the antiviral potential of naturally occurring host defence peptides highlights the potential of a whole new class of molecules to be considered as antiviral therapeutics. Cationic host defence peptides, such as defensins and cathelicidins, are important components of innate immunity with antimicrobial and immunomodulatory capabilities. In recent years they have also been shown to be natural, broad-spectrum antivirals against both enveloped and non-enveloped viruses, including HIV-1, influenza virus, respiratory syncytial virus and herpes simplex virus. Here we review the antiviral properties of several families of these host peptides and their potential to inform the design of novel therapeutics.",2013 May 7,"['Gwyer Findlay, Emily', 'Currie, Silke M.', 'Davidson, Donald J.']",BioDrugs,,,True
d21c15c55bc1ec4daa906cdd848ad037e20c925c,PMC,Combining field epidemiological information and genetic data to comprehensively reconstruct the invasion history and the microevolution of the sudden oak death agent Phytophthora ramorum (Stramenopila: Oomycetes) in California,http://dx.doi.org/10.1007/s10530-013-0453-8,PMC3782357,24078788,NO-CC CODE,"Understanding the migration patterns of invasive organisms is of paramount importance to predict and prevent their further spread. Previous attempts at reconstructing the entire history of the sudden oak death (SOD) epidemic in California were limited by: (1) incomplete sampling; (2) the inability to include infestations caused by a single genotype of the pathogen; (3) collapsing of non-spatially contiguous yet genetically similar samples into large meta-samples that confounded the coalescent analyses. Here, we employ an intensive sampling coverage of 832 isolates of Phytopthora ramorum (the causative agent of SOD) from 60 California forests, genotyped at nine microsatellite loci, to reconstruct its invasion. By using age of infestation as a constraint on coalescent analyses, by dividing genetically indistinguishable meta-populations into highly-resolved sets of spatially contiguous populations, and by using Bruvo genetic distances for most analyses, we reconstruct the entire history of the epidemic and convincingly show infected nursery plants are the original source for the entire California epidemic. Results indicate that multiple human-mediated introductions occurred in most counties and that further disease sources were represented by large wild infestations. The study also identifies minor introductions, some of them relatively recent, linked to infected ornamental plants. Finally, using archival isolates collected soon after the discovery of the pathogen in California, we corroborate that the epidemic is likely to have resulted form 3 to 4 core founder individuals evolved from a single genotype. This is probably the most complete reconstruction ever completed for an invasion by an exotic forest pathogen, and the approach here described may be useful for the reconstruction of invasions by any clonally reproducing organism with a relatively limited natural dispersal range. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10530-013-0453-8) contains supplementary material, which is available to authorized users.",2013 May 29,"['Croucher, Peter J. P.', 'Mascheretti, Silvia', 'Garbelotto, Matteo']",Biol Invasions,,,True
109ac576c495ec3c3f4366c6f0f31d69e9b60dee,PMC,Implementation of an Alert and Response System in Haiti during the Early Stage of the Response to the Cholera Epidemic,http://dx.doi.org/10.4269/ajtmh.13-0267,PMC3795099,24106196,NO-CC CODE,"The start of the cholera epidemic in Haiti quickly highlighted the necessity of the implementation of an Alert and Response (A&R) System to complement the existing national surveillance system. The national system had been able to detect and confirm the outbreak etiology but required external support to monitor the spread of cholera and coordinate response, because much of the information produced was insufficiently timely for real-time monitoring and directing of a rapid, targeted response. The A&R System was designed by the Pan American Health Organization/World Health Organization in collaboration with the Haiti Ministry of Health, and it was based on a network of partners, including any institution, structure, or individual that could identify, verify, and respond to alerts. The defined objectives were to (1) save lives through early detection and treatment of cases and (2) control the spread through early intervention at the community level. The operational structure could be broken down into three principle categories: (1) alert (early warning), (2) verification and assessment of the information, and (3) efficient and timely response in coordination with partners to avoid duplication. Information generated by the A&R System was analyzed and interpreted, and the qualitative information was critical in qualifying the epidemic and defining vulnerable areas, particularly because the national surveillance system reported incomplete data for more than one department. The A&R System detected a number of alerts unrelated to cholera and facilitated rapid access to that information. The sensitivity of the system and its ability to react quickly was shown in May of 2011, when an abnormal increase in alerts coming from several communes in the Sud-Est Department in epidemiological weeks (EWs) 17 and 18 were noted and disseminated network-wide and response activities were implemented. The national cholera surveillance system did not register the increase until EWs 21 and 22, and the information did not become available until EWs 23 and 24, when the peak of cases had already been reached. Although many of the partners reporting alerts during the peak of the cholera epidemic have since left Haiti, the A&R System has continued to function as an Early Warning (EWARN) System, and it continues to be developed with recent activities, such as the distribution of cell phones to enhance alert communication.",2013 Oct 9,"['Santa-Olalla, Patricia', 'Gayer, Michelle', 'Magloire, Roc', 'Barrais, Robert', 'Valenciano, Marta', 'Aramburu, Carmen', 'Poncelet, Jean Luc', 'Gustavo Alonso, Juan Carlos', 'Van Alphen, Dana', 'Heuschen, Florence', 'Andraghetti, Roberta', 'Lee, Robert', 'Drury, Patrick', 'Aldighieri, Sylvain']",Am J Trop Med Hyg,,,True
f54b32b81436b336dfcae7660350b7f488756e0d,PMC,"Fact-finding Survey of Nosocomial Infection Control in Hospitals in Kathmandu, Nepal—A Basis for Improvement",http://dx.doi.org/10.2149/tmh.2013-03,PMC3798410,24155652,NO-CC CODE,"The purpose of this study was to investigate the actual conditions of nosocomial infection control in Kathmandu City, Nepal as a basis for the possible contribution to its improvement. The survey was conducted at 17 hospitals and the methods included a questionnaire, site visits and interviews. Nine hospitals had manuals on nosocomial infection control, and seven had an infection control committee (ICC). The number of hospitals that met the required amount of personal protective equipment preparation was as follows: gowns (13), gloves (13), surgical masks (12). Six hospitals had carried out in-service training over the past one year, but seven hospitals responded that no staff had been trained. Eight hospitals were conducting surveillance based on the results of bacteriological testing. The major problems included inadequate management of ICC, insufficient training opportunities for hospital staff, and lack of essential equipment. Moreover, increasing bacterial resistance to antibiotics was recognized as a growing issue. In comparison with the results conducted in 2003 targeting five governmental hospitals, a steady improvement was observed, but further improvements are needed in terms of the provision of high quality medical care. Particularly, dissemination of appropriate manuals, enhancement of basic techniques, and strengthening of the infection control system should be given priority.",2013 Sep 29,"['Ohara, Hiroshi', 'Pokhrel, Bharat M.', 'Dahal, Rajan K.', 'Mishra, Shyam K.', 'Kattel, Hari P.', 'Shrestha, Dharma L.', 'Haneishi, Yumiko', 'Sherchand, Jeevan B.']",Trop Med Health,,,True
62a0a9024b88c9abef953835a6704042549034ab,PMC,Human coronavirus ocurrence in different populations of Sao Paulo: A comprehensive nine-year study using a pancoronavirus RT-PCR assay,http://dx.doi.org/10.1590/S1517-83822013000100049,PMC3804219,24159325,NO-CC CODE,"Human coronaviruses (HCoVs) are considered one of the most common respiratory viruses associated with respiratory tract illnesses. An emergent human coronavirus was identified as the causal agent of an epidemic of severe acute respiratory syndrome (SARS) during 2002–2003. The severity of the disease combined with its rapid spread requires the continuous surveillance of coronaviruses in worldwide populations. Epidemiological and clinical data of HCoVs infectious in the Brazilian population are scarce and restricted to one or two groups of patients. Our study aimed to investigate retrospectively the presence of HCoVs in different populations of São Paulo presenting acute respiratory tract infections (ARIs) during the years of 2001–2010. A pancoronavirus RT-PCR was performed in this study. Coronaviruses were detected in 126 (11.5%) of 1,087 specimens. Peaks detection frequency was observed during 2002–2004 and 2008–2009, with the highest detection in 2008. The prevalence of HCoVs was higher among children with heart diseases (24.6%), patients under stem cell transplantation program (24.3%) and renal transplanted patients (20.2%). Coryza, cough and fever were the most common symptoms at presentation of positive cases and wheezing, a lower respiratory tract infection symptom was reported by 12% of the total, and 27% of high at-risk patients. HCoVs may have an important role among patients with underlying conditions and transplanted ones.",2013 May 31,"['Cabeça, Tatiane K.', 'Passos, Ana Maria', 'Granato, Celso', 'Bellei, Nancy']",Braz J Microbiol,,,True
30c832e81049d050f9f0c0b4887d0008d86ebc7c,PMC,Prone to survive and the priority rule in science,http://dx.doi.org/10.12659/MSM.889695,PMC3808240,24107784,NO-CC CODE,,2013 Oct 9,"Puliyel, Jacob",Med Sci Monit,,,True
fdc336253485b3b3e895271a27f3457611e826f4,PMC,MicroRNA-based strategy to mitigate the risk of gain-of-function influenza studies,http://dx.doi.org/10.1038/nbt.2666,PMC3808852,23934176,NO-CC CODE,"Recent gain-of-function studies in influenza A virus H5N1 strains revealed that as few as three amino-acid changes in the hemagglutinin protein confer the capacity for viral transmission between ferrets(1, 2). As transmission between ferrets is considered a surrogate indicator of transmissibility between humans, these studies raised concerns about the risks of gain-of-function influenza A virus research. Here we present an approach to strengthen the biosafety of gain-of-function influenza experiments. We exploit species-specific endogenous small RNAs to restrict influenza A virus tropism. In particular, we found that the microRNA miR-192 was expressed in primary human respiratory tract epithelial cells as well as mouse lungs but absent from the ferret respiratory tract. Incorporation of miR-192 target sites into influenza A virus did not prevent influenza replication and transmissibility in ferrets, but did attenuate influenza pathogenicity in mice. This molecular biocontainment approach should be applicable beyond influenza A virus to minimize the risk of experiments involving other pathogenic viruses.",2013 Sep 11,"['Langlois, Ryan A.', 'Albrecht, Randy A.', 'Kimble, Brian', 'Sutton, Troy', 'Shapiro, Jillian S.', 'Finch, Courtney', 'Angel, Matthew', 'Chua, Mark A.', 'Gonzalez-Reiche, Ana Silvia', 'Xu, Kemin', 'Perez, Daniel', 'García-Sastre, Adolfo', 'tenOever, Benjamin R.']",Nat Biotechnol,,,True
b639036a443e2dd13f9c37556011232ff35375ed,PMC,"Declining Influenza Vaccination Coverage among Nurses, Hong Kong, 2006–2012",http://dx.doi.org/10.3201/eid1910.130195,PMC3810738,24047868,NO-CC CODE,"Seasonal influenza vaccination of nurses in Hong Kong fell from 57% in 2005 to 24% in 2012, paralleling concern for adverse reactions associated with vaccination. Decreased acceptance of vaccination was most prominent among nurses who had less work experience and more frequent contact with patients.",2013 Oct,"['Lee, Shui Shan', 'Wong, Ngai Sze', 'Lee, Sing']",Emerg Infect Dis,,,True
df806aba65548a95da899a9663ff3b37fadd3da8,PMC,"Persistent Human Cosavirus Infection in Lung Transplant Recipient, Italy",http://dx.doi.org/10.3201/eid1910.130352,PMC3810744,24047954,NO-CC CODE,Human cosavirus is a novel picornavirus recently identified in feces from children in southern Asia. We report infection with human cosavirus in a patient in the Mediterranean area. The patient was an adult double lung transplant recipient who had chronic diarrhea associated with persistent infection with human cosavirus.,2013 Oct,"['Campanini, Giulia', 'Rovida, Francesca', 'Meloni, Federica', 'Cascina, Alessandro', 'Ciccocioppo, Rachele', 'Piralla, Antonio', 'Baldanti, Fausto']",Emerg Infect Dis,,,True
fcbbd69303b907ba92cb854b46dc2d571e7db2e3,PMC,"Novel Bat Coronaviruses, Brazil and Mexico",http://dx.doi.org/10.3201/eid1910.130525,PMC3810755,24050144,NO-CC CODE,,2013 Oct,"['Góes, Luiz Gustavo Bentim', 'Ruvalcaba, Sicilene Gonzalez', 'Campos, Angélica Almeida', 'Queiroz, Luzia Helena', 'de Carvalho, Cristiano', 'Jerez, José Antonio', 'Durigon, Edison Luiz', 'Dávalos, Luis Ignacio Iñiguez', 'Dominguez, Samuel R.']",Emerg Infect Dis,,,True
361114a078d375c3b8a599835b83f4708eb2ce81,PMC,"Novel Bat Coronaviruses, Brazil and Mexico",http://dx.doi.org/10.3201/eid1910.130525,PMC3810755,24050144,NO-CC CODE,,2013 Oct,"['Góes, Luiz Gustavo Bentim', 'Ruvalcaba, Sicilene Gonzalez', 'Campos, Angélica Almeida', 'Queiroz, Luzia Helena', 'de Carvalho, Cristiano', 'Jerez, José Antonio', 'Durigon, Edison Luiz', 'Dávalos, Luis Ignacio Iñiguez', 'Dominguez, Samuel R.']",Emerg Infect Dis,,,False
e6721f956795bb264b2a66d30e5e6f2145a09193,PMC,"Close Relative of Human Middle East Respiratory Syndrome Coronavirus in Bat, South Africa",http://dx.doi.org/10.3201/eid1910.130946,PMC3810765,24050621,NO-CC CODE,,2013 Oct,"['Ithete, Ndapewa Laudika', 'Stoffberg, Samantha', 'Corman, Victor Max', 'Cottontail, Veronika M.', 'Richards, Leigh Rosanne', 'Schoeman, M. Corrie', 'Drosten, Christian', 'Drexler, Jan Felix', 'Preiser, Wolfgang']",Emerg Infect Dis,,,True
2160b8d1c91659ee78df45256abcf33040016082,PMC,"Close Relative of Human Middle East Respiratory Syndrome Coronavirus in Bat, South Africa",http://dx.doi.org/10.3201/eid1910.130946,PMC3810765,24050621,NO-CC CODE,,2013 Oct,"['Ithete, Ndapewa Laudika', 'Stoffberg, Samantha', 'Corman, Victor Max', 'Cottontail, Veronika M.', 'Richards, Leigh Rosanne', 'Schoeman, M. Corrie', 'Drosten, Christian', 'Drexler, Jan Felix', 'Preiser, Wolfgang']",Emerg Infect Dis,,,False
f1382d2d476137ce89455675b6a2eb68a485ebac,PMC,Management strategies in the treatment of neonatal and pediatric gastroenteritis,http://dx.doi.org/10.2147/IDR.S12718,PMC3815002,24194646,NO-CC CODE,"Acute gastroenteritis, characterized by the onset of diarrhea with or without vomiting, continues to be a major cause of morbidity and mortality in children in mostly resource-constrained nations. Although generally a mild and self-limiting disease, gastroenteritis is one of the most common causes of hospitalization and is associated with a substantial disease burden. Worldwide, up to 40% of children aged less than 5 years with diarrhea are hospitalized with rotavirus. Also, some microorganisms have been found predominantly in resource-constrained nations, including Shigella spp, Vibrio cholerae, and the protozoan infections. Prevention remains essential, and the rotavirus vaccines have demonstrated good safety and efficacy profiles in large clinical trials. Because dehydration is the major complication associated with gastroenteritis, appropriate fluid management (oral or intravenous) is an effective and safe strategy for rehydration. Continuation of breastfeeding is strongly recommended. New treatments such as antiemetics (ondansetron), some antidiarrheal agents (racecadotril), and chemotherapeutic agents are often proposed, but not yet universally recommended. Probiotics, also known as “food supplement,” seem to improve intestinal microbial balance, reducing the duration and the severity of acute infectious diarrhea. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the European Society of Paediatric Infectious Diseases guidelines make a stronger recommendation for the use of probiotics for the management of acute gastroenteritis, particularly those with documented efficacy such as Lactobacillus rhamnosus GG, Lactobacillus reuteri, and Saccharomyces boulardii. To date, the management of acute gastroenteritis has been based on the option of “doing the least”: oral rehydration-solution administration, early refeeding, no testing, no unnecessary drugs.",2013 Oct 29,"['Ciccarelli, Simona', 'Stolfi, Ilaria', 'Caramia, Giuseppe']",Infect Drug Resist,,,True
db055944a3acc538005fe7af772ec33c16b2fdd9,PMC,Vaccines for the future: learning from human immunology,http://dx.doi.org/10.1111/j.1751-7915.2011.00276.x,PMC3815775,21880117,NO-CC CODE,"Conventional vaccines have been extremely successful in preventing infections by pathogens expressing relatively conserved antigens through antibody‐mediated effector mechanisms. Thanks to vaccination some diseases have been eradicated and mortality due to infectious diseases has been significantly reduced. However, there are still many infections that are not preventable with vaccination, which represent a major cause of mortality worldwide. Some of these infections are caused by pathogens with a high degree of antigen variability that cannot be controlled only by antibodies, but require a mix of humoral and cellular immune responses. Novel technologies for antigen discovery, expression and formulation allow now for the development of vaccines that can better cope with pathogen diversity and trigger multifunctional immune responses. In addition, the application of new genomic assays and systems biology approaches in human immunology can help to better identify vaccine correlates of protection. The availability of novel vaccine technologies, together with the knowledge of the distinct human immune responses that are required to prevent different types of infection, should help to rationally design effective vaccines where conventional approaches have failed.",2012 Mar 20,"['De Gregorio, Ennio', 'Rappuoli, Rino']",Microb Biotechnol,,,True
cdb6748d297a7329b905186e48611af6d932b62f,PMC,Nanoparticles for transcutaneous vaccination,http://dx.doi.org/10.1111/j.1751-7915.2011.00284.x,PMC3815776,21854553,NO-CC CODE,"The living epidermis and dermis are rich in antigen presenting cells (APCs). Their activation can elicit a strong humoral and cellular immune response as well as mucosal immunity. Therefore, the skin is a very attractive site for vaccination, and an intradermal application of antigen may be much more effective than a subcutaneous or intramuscular injection. However, the stratum corneum (SC) is a most effective barrier against the invasion of topically applied vaccines. Products which have reached the stage of clinical testing, avoid this problem by injecting the nano‐vaccine intradermally or by employing a barrier disrupting method and applying the vaccine to a relatively large skin area. Needle‐free vaccination is desirable from a number of aspects: ease of application, improved patient acceptance and less risk of infection among them. Nanocarriers can be designed in a way that they can overcome the SC. Also incorporation into nanocarriers protects instable antigen from degradation, improves uptake and processing by APCs, and facilitates endosomal escape and nuclear delivery of DNA vaccines. In addition, sustained release systems may build a depot in the tissue gradually releasing antigen which may avoid booster doses. Therefore, nanoformulations of vaccines for transcutaneous immunization are currently a very dynamic field of research. Among the huge variety of nanocarrier systems that are investigated hopes lie on ultra‐flexible liposomes, superfine rigid nanoparticles and nanocarriers, which are taken up by hair follicles. The potential and pitfalls associated with these three classes of carriers will be discussed.",2012 Mar 20,"['Hansen, Steffi', 'Lehr, Claus‐Michael']",Microb Biotechnol,,,True
442483b51febb0ef0cedea0d4283da1cb8c7ec01,PMC,The future of biological warfare,http://dx.doi.org/10.1111/j.1751-7915.2012.00340.x,PMC3815869,22432943,NO-CC CODE,,2012 Sep 24,"Casadevall, Arturo",Microb Biotechnol,,,True
9881cbf87faaee63ada0713e3a8953d3732e0f12,PMC,Targeting and retention of HPV16 E7 to the endoplasmic reticulum enhances immune tumour protection,http://dx.doi.org/10.1111/j.1582-4934.2009.00934.x,PMC3823120,19818090,NO-CC CODE,"The endoplasmic reticulum (ER) is where the major histocompatibility complex (MHC) class I molecules are loaded with epitopes to cause an immune cellular response. Most of the protein antigens are degraded in the cytoplasm to amino acids and few epitopes reach the ER. Antigen targeting of this organelle by Calreticulin (CRT) fusion avoids this degradation and enhances the immune response. We constructed a recombinant adenovirus to express the E7 antigen with an ER-targeting signal peptide (SP) plus an ER retention signal (KDEL sequence). In cell-culture experiments we demonstrated that this new E7 antigen, SP-E7-KDEL, targeted the ER. Infection of mice with this recombinant adenovirus that expresses SP-E7-KDEL showed interferon induction and tumour-protection response, similar to that provided by an adenovirus expressing the E7 antigen fused to CRT. This work demonstrated that just by adding a SP and the KDEL sequence, antigens can be targeted and retained in the ER with a consequent enhancement of immune response and tumour protection. These results will have significant clinical applications.",2010 Apr 10,"['Loera-Arias, MJ', 'Martínez-Pérez, AG', 'Barrera-Hernández, A', 'Ibarra-Obregón, ER', 'González-Saldívar, G', 'Martínez-Ortega, JI', 'Rosas-Taraco, A', 'Villanueva-Olivo, A', 'Esparza-González, SC', 'Villatoro-Hernandez, J', 'Saucedo-Cárdenas, O', 'Montes-de-Oca-Luna, R']",J Cell Mol Med,,,True
8b622c10da164694e7148158875599c31f460b82,PMC,"Docking, virtual high throughput screening and in silico fragment-based drug design",http://dx.doi.org/10.1111/j.1582-4934.2008.00665.x,PMC3823351,19183238,NO-CC CODE,"The drug discovery process has been profoundly changed recently by the adoption of computational methods helping the design of new drug candidates more rapidly and at lower costs. In silico drug design consists of a collection of tools helping to make rational decisions at the different steps of the drug discovery process, such as the identification of a biomolecular target of therapeutical interest, the selection or the design of new lead compounds and their modification to obtain better affinities, as well as pharmacokinetic and pharmacodynamic properties. Among the different tools available, a particular emphasis is placed in this review on molecular docking, virtual high-throughput screening and fragment-based ligand design.",2009 Feb 21,"['Zoete, Vincent', 'Grosdidier, Aurélien', 'Michielin, Olivier']",J Cell Mol Med,,,True
db59c00ca304cff50531d66511fcf971f97a53ec,PMC,Identification of pathogens and virulence profile of Rhodococcus equi and Escherichia coli strains obtained from sand of parks,http://dx.doi.org/10.1590/S1517-83822013005000044,PMC3833150,24294244,NO-CC CODE,"The identification of pathogens of viral (Rotavirus, Coronavirus), parasitic (Toxocara spp.) and bacterial (Escherichia coli, Salmonella spp., Rhodococcus equi) origin shed in feces, and the virulence profile of R. equi and E. coli isolates were investigated in 200 samples of sand obtained from 40 parks, located in central region of state of Sao Paulo, Brazil, using different diagnostic methods. From 200 samples analyzed, 23 (11.5%) strains of R. equi were isolated. None of the R. equi isolates showed a virulent (vapA gene) or intermediately virulent (vapB gene) profiles. Sixty-three (31.5%) strains of E. coli were identified. The following genes encoding virulence factors were identified in E. coli: eae, bfp, saa, iucD, papGI, sfa and hly. Phylogenetic classification showed that 63 E. coli isolates belonged to groups B1 (52.4%), A (25.4%) and B2 (22.2%). No E. coli serotype O157:H7 was identified. Eggs of Toxocara sp. were found in three parks and genetic material of bovine Coronavirus was identified in one sample of one park. No Salmonella spp. and Rotavirus isolates were identified in the samples of sand. The presence of R. equi, Toxocara sp, bovine Coronavirus and virulent E. coli isolates in the environment of parks indicates that the sanitary conditions of the sand should be improved in order to reduce the risks of fecal transmission of pathogens of zoonotic potential to humans in these places.",2013 Oct 30,"['Fernandes, M.C.', 'Takai, S.', 'Leite, D.S.', 'Pinto, J.P.A.N.', 'Brandão, P.E.', 'Santarém, V.A.', 'Listoni, F.J.P.', 'Da Silva, A.V.', 'Ribeiro, M.G.']",Braz J Microbiol,,,True
76f130b68624f44fc610de3deae25f2ba703b304,PMC,Systems Biology and Biomarker Discovery,http://dx.doi.org/10.3233/DMA-2010-0706,PMC3833237,20534904,NO-CC CODE,,2010 Jun 9,"Rodland, Karin D.",Dis Markers,,,True
3399d0fe01c7cb8bff0615a506b7beacc813a05e,PMC,Systems Biology Approaches to Disease Marker Discovery,http://dx.doi.org/10.3233/DMA-2010-0707,PMC3833409,20534906,NO-CC CODE,"Our understanding of human disease and potential therapeutics is improving rapidly. In order to take advantage of these developments it is important to be able to identify disease markers. Many new high-throughput genomics and proteomics technologies are being implemented to identify candidate disease markers. These technologies include protein microarrays, next-generation DNA sequencing and mass spectrometry platforms. Such methods are particularly important for elucidating the repertoire of molecular markers in the genome, transcriptome, proteome and metabolome of patients with diseases such as cancer, autoimmune diseases, and viral infections, resulting from the disruption of many biological pathways. These new technologies have identified many potential disease markers. These markers are expected to be valuable to achieve the promise of truly personalized medicine.",2010 Jun 9,"['Sharon, Donald', 'Chen, Rui', 'Snyder, Michael']",Dis Markers,,,True
285fac85e3bda953636c45b1e600f9e60540938d,PMC,Increased Flavonoid Compounds from Fermented Houttuynia cordata using Isolated Six of Bacillus from Traditionally Fermented Houttuynia cordata,http://dx.doi.org/10.5487/TR.2012.28.2.117,PMC3834406,24278599,NO-CC CODE,"Flavonoids, which form a major component in Houttuynia cordata Thunb., display a wide range of pharmacological activities. The expression of plant flavonoids is partly regulated by fermentation. Therefore, we studied the effects of fermentation on H. cordata in order to identify the strains present during the fermentation process, and to determine whether fermented H. cordata could be used as a probiotic. Our results showed that all 6 of the bacterial strains isolated from fermented H. cordata (FHC) belonged to the genus Bacillus. As expected, fermenting H cordata also increased the flavonoid content as increases were observed in the levels of rutin, quercitrin, and quercetin. To test the effects of fermentation, we treated LPS-stimulated RAW264.7 cells with non-fermented H. cordata extracts (HCE) or FHC extracts (FHCE). Compared to the HCE-treated cells, the FHCE-treated cells showed increased viability. No cytotoxic effects were detected in the FHCE-treated groups in the 2 cell lines used in the study, namely, RAW264.7 and RBL-2H3. FHCE-treated HepG2 cells showed decreased growth, compared to HCE-treated HepG2 cells. These results indicate that the fermented H. cordata predominantly contained Bacillus strains. Furthermore, FHCE are able to prevent LPS-induced inflammatory effects and inhibit the growth of HepG2 cells.",2012 Jun,"['Kwon, Ryun Hee', 'Ha, Bae Jin']",Toxicol Res,,,True
7051169cee12dbca19764986a24af534e60c3ab4,PMC,Machine learning approach identifies new pathways associated with demyelination in a viral model of multiple sclerosis,http://dx.doi.org/10.1111/j.1582-4934.2008.00646.x,PMC3837619,19183246,NO-CC CODE,"Theiler’s murine encephalomyelitis is an experimentally virus-induced inflammatory demyelinating disease of the spinal cord, displaying clinical and pathological similarities to chronic progressive multiple sclerosis. The aim of this study was to identify pathways associated with chronic demyelination using an assumption-free combined microarray and immunohistology approach. Movement control as determined by rotarod assay significantly worsened in Theiler’s murine encephalomyelitis -virus-infected SJL/J mice from 42 to 196 days after infection (dpi). In the spinal cords, inflammatory changes were detected 14 to 196 dpi, and demyelination progressively increased from 42 to 196 dpi. Microarray analysis revealed 1001 differentially expressed genes over the study period. The dominating changes as revealed by k-means and functional annotation clustering included up-regulations related to intrathecal antibody production and antigen processing and presentation via major histocompatibility class II molecules. A random forest machine learning algorithm revealed that down-regulated lipid and cholesterol biosynthesis, differentially expressed neurite morphogenesis and up-regulated toll-like receptor-4-induced pathways were intimately associated with demyelination as measured by immunohistology. Conclusively, although transcriptional changes were dominated by the adaptive immune response, the main pathways associated with demyelination included up-regulation of toll-like receptor 4 and down-regulation of cholesterol biosynthesis. Cholesterol biosynthesis is a rate limiting step of myelination and its down-regulation is suggested to be involved in chronic demyelination by an inhibition of remyelination.",2010 Jan 14 Jan-Feb,"['Ulrich, Reiner', 'Kalkuhl, Arno', 'Deschl, Ulrich', 'Baumgärtner, Wolfgang']",J Cell Mol Med,,,True
60a0f190f79987eaf2d5bbe5e2e48b85161caaa9,PMC,"Use of National Pneumonia Surveillance to Describe Influenza A(H7N9) Virus Epidemiology, China, 2004–2013",http://dx.doi.org/10.3201/eid1911.130865,PMC3837642,24206646,NO-CC CODE,"In mainland China, most avian influenza A(H7N9) cases in the spring of 2013 were reported through the pneumonia of unknown etiology (PUE) surveillance system. To understand the role of possible underreporting and surveillance bias in assessing the epidemiology of subtype H7N9 cases and the effect of live-poultry market closures, we examined all PUE cases reported from 2004 through May 3, 2013. Historically, the PUE system was underused, reporting was inconsistent, and PUE reporting was biased toward A(H7N9)-affected provinces, with sparse data from unaffected provinces; however, we found no evidence that the older ages of persons with A(H7N9) resulted from surveillance bias. The absolute number and the proportion of PUE cases confirmed to be A(H7N9) declined after live-poultry market closures (p<0.001), indicating that market closures might have positively affected outbreak control. In China, PUE surveillance needs to be improved.",2013 Nov,"['Xiang, Nijuan', 'Havers, Fiona', 'Chen, Tao', 'Song, Ying', 'Tu, Wenxiao', 'Li, Leilei', 'Cao, Yang', 'Liu, Bo', 'Zhou, Lei', 'Meng, Ling', 'Hong, Zhiheng', 'Wang, Rui', 'Niu, Yan', 'Yao, Jianyi', 'Liao, Kaiju', 'Jin, Lianmei', 'Zhang, Yanping', 'Li, Qun', 'Widdowson, Marc-Alain', 'Feng, Zijian']",Emerg Infect Dis,,,True
9595fe80c8e79a20286b0bfad42c930623e13805,PMC,"Middle East Respiratory Syndrome Coronavirus in Bats, Saudi Arabia",http://dx.doi.org/10.3201/eid1911.131172,PMC3837665,24206838,NO-CC CODE,The source of human infection with Middle East respiratory syndrome coronavirus remains unknown. Molecular investigation indicated that bats in Saudi Arabia are infected with several alphacoronaviruses and betacoronaviruses. Virus from 1 bat showed 100% nucleotide identity to virus from the human index case-patient. Bats might play a role in human infection.,2013 Nov,"['Memish, Ziad A.', 'Mishra, Nischay', 'Olival, Kevin J.', 'Fagbo, Shamsudeen F.', 'Kapoor, Vishal', 'Epstein, Jonathan H.', 'AlHakeem, Rafat', 'Durosinloun, Abdulkareem', 'Al Asmari, Mushabab', 'Islam, Ariful', 'Kapoor, Amit', 'Briese, Thomas', 'Daszak, Peter', 'Al Rabeeah, Abdullah A.', 'Lipkin, W. Ian']",Emerg Infect Dis,,,True
eaceb9c0b3330a958c786c5fa07673d744269070,PMC,"Schmallenberg Virus Infection in Dogs, France, 2012",http://dx.doi.org/10.3201/eid1911.130464,PMC3837666,24209712,NO-CC CODE,,2013 Nov,"['Sailleau, Corinne', 'Boogaerts, Cassandre', 'Meyrueix, Anne', 'Laloy, Eve', 'Bréard, Emmanuel', 'Viarouge, Cyril', 'Desprat, Alexandra', 'Vitour, Damien', 'Doceul, Virginie', 'Boucher, Catherine', 'Zientara, Stéphan', 'Nicolier, Alexandra', 'Grandjean, Dominique']",Emerg Infect Dis,,,True
b553ae7b38c105bfb4182ec31b51c9a24ed501cf,PMC,"Surveillance for Avian Influenza A(H7N9), Beijing, China, 2013",http://dx.doi.org/10.3201/eid1912.130983,PMC3840857,24274700,NO-CC CODE,"During surveillance for pneumonia of unknown etiology and sentinel hospital–based surveillance in Beijing, China, we detected avian influenza A(H7N9) virus infection in 4 persons who had pneumonia, influenza-like illness, or asymptomatic infections. Samples from poultry workers, associated poultry environments, and wild birds suggest that this virus might not be present in Beijing.",2013 Dec,"['Yang, Peng', 'Pang, Xinghuo', 'Deng, Ying', 'Ma, Chunna', 'Zhang, Daitao', 'Sun, Ying', 'Shi, Weixian', 'Lu, Guilan', 'Zhao, Jiachen', 'Liu, Yimeng', 'Peng, Xiaomin', 'Tian, Yi', 'Qian, Haikun', 'Chen, Lijuan', 'Wang, Quanyi']",Emerg Infect Dis,,,True
1e2678ba55265e7afbeee0af9b5dee86342f85f6,PMC,"Novel Orthoreovirus from Mink, China, 2011",http://dx.doi.org/10.3201/eid1912.130043,PMC3840883,24274037,NO-CC CODE,"We identified a novel mink orthoreovirus, MRV1HB-A, which seems to be closely related to human strain MRV2tou05, which was isolated from 2 children with acute necrotizing encephalopathy in 2005. Evolution of this virus should be closely monitored so that prevention and control measures can be taken should it become more virulent.",2013 Dec,"['Lian, Hai', 'Liu, Ye', 'Zhang, Shoufeng', 'Zhang, Fei', 'Hu, Rongliang']",Emerg Infect Dis,,,True
b4e7d6a06b8a5eef40f477b8c2fe42640cf45ffc,PMC,"Novel Orthoreovirus from Mink, China, 2011",http://dx.doi.org/10.3201/eid1912.130043,PMC3840883,24274037,NO-CC CODE,"We identified a novel mink orthoreovirus, MRV1HB-A, which seems to be closely related to human strain MRV2tou05, which was isolated from 2 children with acute necrotizing encephalopathy in 2005. Evolution of this virus should be closely monitored so that prevention and control measures can be taken should it become more virulent.",2013 Dec,"['Lian, Hai', 'Liu, Ye', 'Zhang, Shoufeng', 'Zhang, Fei', 'Hu, Rongliang']",Emerg Infect Dis,,,False
329cff721b7b30ea14537ac2a85254cd984691db,PMC,Savage Nature and Ecologic Exchange,http://dx.doi.org/10.3201/eid1912.AC1912,PMC3840887,,NO-CC CODE,,2013 Dec,"Potter, Polyxeni",Emerg Infect Dis,,,True
5df6a629545e9d444c3ee76b24095606a25e48e1,PMC,"Porcine Epidemic Diarrhea Virus Variants with High Pathogenicity, China",http://dx.doi.org/10.3201/eid1912.121088,PMC3840889,24274832,NO-CC CODE,,2013 Dec,"['Wang, Jinbao', 'Zhao, Pengwei', 'Guo, Lihui', 'Liu, Yueyue', 'Du, Yijun', 'Ren, Sufang', 'Li, Jun', 'Zhang, Yuyu', 'Fan, Yufeng', 'Huang, Baohua', 'Liu, Sidang', 'Wu, Jiaqiang']",Emerg Infect Dis,,,True
b52cbe9e88f7e6f760270317dc1ff03b49aaae0d,PMC,"Porcine Epidemic Diarrhea Virus Variants with High Pathogenicity, China",http://dx.doi.org/10.3201/eid1912.121088,PMC3840889,24274832,NO-CC CODE,,2013 Dec,"['Wang, Jinbao', 'Zhao, Pengwei', 'Guo, Lihui', 'Liu, Yueyue', 'Du, Yijun', 'Ren, Sufang', 'Li, Jun', 'Zhang, Yuyu', 'Fan, Yufeng', 'Huang, Baohua', 'Liu, Sidang', 'Wu, Jiaqiang']",Emerg Infect Dis,,,False
306e80d6a8f3885d871f6b16cdce1bd19f9a70c2,PMC,"Distinct Lineage of Vesiculovirus from Big Brown Bats, United States",http://dx.doi.org/10.3201/eid1912.121506,PMC3840891,24274823,NO-CC CODE,"We identified a novel rhabdovirus, American bat vesiculovirus, from postmortem tissue samples from 120 rabies-negative big brown bats with a history of human contact. Five percent of the tested bats were infected with this virus. The extent of zoonotic exposure and possible health effects in humans from this virus are unknown.",2013 Dec,"['Ng, Terry Fei Fan', 'Driscoll, Cindy', 'Carlos, Maria Paz', 'Prioleau, Algernon', 'Schmieder, Robert', 'Dwivedi, Bhakti', 'Wong, Jakk', 'Cha, Yunhee', 'Head, Steven', 'Breitbart, Mya', 'Delwart, Eric']",Emerg Infect Dis,,,True
cdcd1d3772530b841701af3e7c01226fed60655a,PMC,"Distinct Lineage of Vesiculovirus from Big Brown Bats, United States",http://dx.doi.org/10.3201/eid1912.121506,PMC3840891,24274823,NO-CC CODE,"We identified a novel rhabdovirus, American bat vesiculovirus, from postmortem tissue samples from 120 rabies-negative big brown bats with a history of human contact. Five percent of the tested bats were infected with this virus. The extent of zoonotic exposure and possible health effects in humans from this virus are unknown.",2013 Dec,"['Ng, Terry Fei Fan', 'Driscoll, Cindy', 'Carlos, Maria Paz', 'Prioleau, Algernon', 'Schmieder, Robert', 'Dwivedi, Bhakti', 'Wong, Jakk', 'Cha, Yunhee', 'Head, Steven', 'Breitbart, Mya', 'Delwart, Eric']",Emerg Infect Dis,,,True
70192ccdd02a91b15853fd3556114d83f88cc4d5,PMC,"Lack of MERS Coronavirus Neutralizing Antibodies in Humans, Eastern Province, Saudi Arabia",http://dx.doi.org/10.3201/eid1912.130701,PMC3840893,24274664,NO-CC CODE,"We used a lentiviral vector bearing the viral spike protein to detect neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) in persons from the Eastern Province of Saudi Arabia. None of the 268 samples tested displayed neutralizing activity, which suggests that MERS-CoV infections in humans are infrequent in this province.",2013 Dec,"['Gierer, Stefanie', 'Hofmann-Winkler, Heike', 'Albuali, Waleed H.', 'Bertram, Stephanie', 'Al-Rubaish, Abdullah M.', 'Yousef, Abdullah A.', 'Al-Nafaie, Awatif N.', 'Al-Ali, Amein K.', 'Obeid, Obeid E.', 'Alkharsah, Khaled R.', 'Pöhlmann, Stefan']",Emerg Infect Dis,,,True
b48d63ad65555f3c41a482332d3a9971ab28bc00,PMC,Massively parallel pathogen identification using high‐density microarrays,http://dx.doi.org/10.1111/j.1751-7915.2007.00012.x,PMC3864434,21261824,NO-CC CODE,"Identification of microbial pathogens in clinical specimens is still performed by phenotypic methods that are often slow and cumbersome, despite the availability of more comprehensive genotyping technologies. We present an approach based on whole‐genome amplification and resequencing microarrays for unbiased pathogen detection. This 10 h process identifies a broad spectrum of bacterial and viral species and predicts antibiotic resistance and pathogenicity and virulence profiles. We successfully identify a variety of bacteria and viruses, both in isolation and in complex mixtures, and the high specificity of the microarray distinguishes between different pathogens that cause diseases with overlapping symptoms. The resequencing approach also allows identification of organisms whose sequences are not tiled on the array, greatly expanding the repertoire of identifiable organisms and their variants. We identify organisms by hybridization of their DNA in as little as 1–4 h. Using this method, we identified Monkeypox virus and drug‐resistant Staphylococcus aureus in a skin lesion taken from a child suspected of an orthopoxvirus infection, despite poor transport conditions of the sample, and a vast excess of human DNA. Our results suggest this technology could be applied in a clinical setting to test for numerous pathogens in a rapid, sensitive and unbiased manner.",2008 Jan 22,"['Berthet, Nicolas', 'Dickinson, Philip', 'Filliol, Ingrid', 'Reinhardt, Anita K.', 'Batejat, Christophe', 'Vallaeys, Tatiana', 'Kong, Katherine A.', 'Davies, Christopher', 'Lee, Walter', 'Zhang, Shenglan', 'Turpaz, Yaron', 'Heym, Beate', 'Coralie, Gilberte', 'Dacheux, Laurent', 'Burguière, Ana Maria', 'Bourhy, Hervé', 'Old, Iain G.', 'Manuguerra, Jean‐Claude', 'Cole, Stewart T.', 'Kennedy, Giulia C.']",Microb Biotechnol,,,True
f16e75ea1eeb18f86b4e113796cabc4c7c78621a,PMC,Massively parallel pathogen identification using high‐density microarrays,http://dx.doi.org/10.1111/j.1751-7915.2007.00012.x,PMC3864434,21261824,NO-CC CODE,"Identification of microbial pathogens in clinical specimens is still performed by phenotypic methods that are often slow and cumbersome, despite the availability of more comprehensive genotyping technologies. We present an approach based on whole‐genome amplification and resequencing microarrays for unbiased pathogen detection. This 10 h process identifies a broad spectrum of bacterial and viral species and predicts antibiotic resistance and pathogenicity and virulence profiles. We successfully identify a variety of bacteria and viruses, both in isolation and in complex mixtures, and the high specificity of the microarray distinguishes between different pathogens that cause diseases with overlapping symptoms. The resequencing approach also allows identification of organisms whose sequences are not tiled on the array, greatly expanding the repertoire of identifiable organisms and their variants. We identify organisms by hybridization of their DNA in as little as 1–4 h. Using this method, we identified Monkeypox virus and drug‐resistant Staphylococcus aureus in a skin lesion taken from a child suspected of an orthopoxvirus infection, despite poor transport conditions of the sample, and a vast excess of human DNA. Our results suggest this technology could be applied in a clinical setting to test for numerous pathogens in a rapid, sensitive and unbiased manner.",2008 Jan 22,"['Berthet, Nicolas', 'Dickinson, Philip', 'Filliol, Ingrid', 'Reinhardt, Anita K.', 'Batejat, Christophe', 'Vallaeys, Tatiana', 'Kong, Katherine A.', 'Davies, Christopher', 'Lee, Walter', 'Zhang, Shenglan', 'Turpaz, Yaron', 'Heym, Beate', 'Coralie, Gilberte', 'Dacheux, Laurent', 'Burguière, Ana Maria', 'Bourhy, Hervé', 'Old, Iain G.', 'Manuguerra, Jean‐Claude', 'Cole, Stewart T.', 'Kennedy, Giulia C.']",Microb Biotechnol,,,True
659dbc689ddfded5d655534f1e03041279f3942d,PMC,Massively parallel pathogen identification using high‐density microarrays,http://dx.doi.org/10.1111/j.1751-7915.2007.00012.x,PMC3864434,21261824,NO-CC CODE,"Identification of microbial pathogens in clinical specimens is still performed by phenotypic methods that are often slow and cumbersome, despite the availability of more comprehensive genotyping technologies. We present an approach based on whole‐genome amplification and resequencing microarrays for unbiased pathogen detection. This 10 h process identifies a broad spectrum of bacterial and viral species and predicts antibiotic resistance and pathogenicity and virulence profiles. We successfully identify a variety of bacteria and viruses, both in isolation and in complex mixtures, and the high specificity of the microarray distinguishes between different pathogens that cause diseases with overlapping symptoms. The resequencing approach also allows identification of organisms whose sequences are not tiled on the array, greatly expanding the repertoire of identifiable organisms and their variants. We identify organisms by hybridization of their DNA in as little as 1–4 h. Using this method, we identified Monkeypox virus and drug‐resistant Staphylococcus aureus in a skin lesion taken from a child suspected of an orthopoxvirus infection, despite poor transport conditions of the sample, and a vast excess of human DNA. Our results suggest this technology could be applied in a clinical setting to test for numerous pathogens in a rapid, sensitive and unbiased manner.",2008 Jan 22,"['Berthet, Nicolas', 'Dickinson, Philip', 'Filliol, Ingrid', 'Reinhardt, Anita K.', 'Batejat, Christophe', 'Vallaeys, Tatiana', 'Kong, Katherine A.', 'Davies, Christopher', 'Lee, Walter', 'Zhang, Shenglan', 'Turpaz, Yaron', 'Heym, Beate', 'Coralie, Gilberte', 'Dacheux, Laurent', 'Burguière, Ana Maria', 'Bourhy, Hervé', 'Old, Iain G.', 'Manuguerra, Jean‐Claude', 'Cole, Stewart T.', 'Kennedy, Giulia C.']",Microb Biotechnol,,,True
c64895008556e2b29bdd88524b8be2e54ed5abe9,PMC,"Novel Avian Coronavirus and Fulminating Disease in Guinea Fowl, France",http://dx.doi.org/10.3201/eid2001.130774,PMC3884723,24377831,NO-CC CODE,"For decades, French guinea fowl have been affected by fulminating enteritis of unclear origin. By using metagenomics, we identified a novel avian gammacoronavirus associated with this disease that is distantly related to turkey coronaviruses. Fatal respiratory diseases in humans have recently been caused by coronaviruses of animal origin.",2014 Jan,"['Liais, Etienne', 'Croville, Guillaume', 'Mariette, Jérôme', 'Delverdier, Maxence', 'Lucas, Marie-Noëlle', 'Klopp, Christophe', 'Lluch, Jérôme', 'Donnadieu, Cécile', 'Guy, James S.', 'Corrand, Léni', 'Ducatez, Mariette F.', 'Guérin, Jean-Luc']",Emerg Infect Dis,,,True
a410689981eddf53ed0073a2310941bb37913ab9,PMC,Activity of sputum p38 MAPK is correlated with airway inflammation and reduced FEV(1) in COPD patients,http://dx.doi.org/10.12659/MSM.889880,PMC3890402,24382347,NO-CC CODE,"BACKGROUND: Inflammation and remodeling of the small airways are major determinants of the progression and severity of COPD. The present study explored the correlation between sputum p38 mitogen-activated protein kinase (MAPK) activity and airway inflammation and reduction of lung function in the patients with chronic obstructive pulmonary disease (COPD). MATERIAL/METHODS: Sputum samples were collected from 48 COPD patients and 12 healthy persons. Sputum p38 MAPK activity was measured by Western blotting and sputum levels of CXCL8 and neutrophil, and lung function was measured. The correlation between p38MAPK activity and airway inflammation and reduction of lung function was analyzed. RESULT: Our results showed the significantly increased expression of phospho-p38 MAPK and CXCL8 in the sputum samples of the COPD patients. The p38 MAPK activity was remarkably correlated with the CXCL8 level and neutrophils infiltration in the airway, and the decline of lung function in the COPD patients. CONCLUSIONS: These findings suggest the pivotal role of p38 MAPK in the airway inflammation of COPD patients. We propose p38 MAPK as a potential target for the treatment of COPD.",2013 Dec 31,"['Huang, Cuiping', 'Xie, Moying', 'He, Xinhua', 'Gao, Hui']",Med Sci Monit,,,True
2c22051b7eac78f942e796dd838481e126eebeba,PMC,Welcome to Infectious Disease Reports: a message from the Editor,http://dx.doi.org/10.4081/idr.2009.e1,PMC3892566,24470879,NO-CC CODE,,2009 Sep 14,"Aronoff, David M",Infect Dis Rep,,,False
c3d3ee0b012a09d8de42c13d046f42ebd291e76e,PMC,Human metapneumovirus and respiratory syncytial virus: subtle differences but comparable severity,http://dx.doi.org/10.4081/idr.2010.e12,PMC3892583,24470892,NO-CC CODE,"Human metapneumovirus (hMPV) is a recently discovered virus that causes respiratory illness in children that can lead to hospitalization. Our study was undertaken to further understand hMPV-associated illness, compare clinical characteristics of hMPV and respiratory syncytial virus (RSV), and establish the utility of routine screening for hMPV. We retrospectively identified hMPV-associated illnesses described among children with respiratory symptoms admitted to a tertiary care center in southeast Michigan during the 2006–2007 respiratory viral season. A convenience sample of 256 nasopharyngeal specimens was subjected to nucleic acid extraction and amplification to identify those specimens positive for hMPV. A medical record review was undertaken to retrieve demographic and clinical data of patients with hMPV, comparing them to RSV-positive patients and patients evaluated for respiratory symptoms who were negative for hMPV and RSV. We found that hMPV was the second most commonly identified virus after RSV. hMPV-positive patients were older than RSV-positive patients. Among hMPV-positive patients, pneumonia was diagnosed in 37.5% and bronchiolitis in 31.2%, peribronchial cuffing was present on chest radiographs of 37.5%, antibiotic treatment was used in 81.2%, and admission to the ICU was seen in 37.5%. Finally, hMPV-positive patients were more likely to have fever than RSV-positive patients or patients negative for hMPV and RSV. We concluded that hMPV is a major pathogen associated with hospitalization of children and with the same severity of illness as RSV but in a slightly older population. Because of the apparent prevalence and severity of illness, routine screening should be implemented.",2010 Aug 11,"['Akhras, Nour', 'Weinberg, Jason B.', 'Newton, Duane']",Infect Dis Rep,,,True
d83a2c20f409e7be9dbe6e9c8c62ddaf2b506c48,PMC,The severe acute respiratory syndrome epidemic in mainland China dissected,http://dx.doi.org/10.4081/idr.2011.e2,PMC3892599,24470901,NO-CC CODE,"This paper provides a review of a recently published series of studies that give a detailed and comprehensive documentation of the severe acute respiratory syndrome (SARS) epidemic in mainland China, which severely struck the country in the spring of 2003. The epidemic spanned a large geographical extent but clustered in two areas: first in Guangdong Province, and about 3 months later in Beijing with its surrounding areas. Reanalysis of all available epidemiological data resulted in a total of 5327 probable cases of SARS, of whom 343 died. The resulting case fatality ratio (CFR) of 6.4% was less than half of that in other SARS-affected countries or areas, and this difference could only partly be explained by younger age of patients and higher number of community acquired infections. Analysis of the impact of interventions demonstrated that strong political commitment and a centrally coordinated response was the most important factor to control SARS in mainland China, whereas the most stringent control measures were all initiated when the epidemic was already dying down. The long-term economic consequence of the epidemic was limited, much consumption was merely postponed, but for Beijing irrecoverable losses to the tourist sector were considerable. An important finding from a cohort study was that many former SARS patients currently suffer from avascular osteonecrosis, as a consequence of the treatment with corticosteroids during their infection. The SARS epidemic provided valuable information and lessons relevant in controlling outbreaks of newly emerging infectious diseases, and has led to fundamental reforms of the Chinese health system. In particular, a comprehensive nationwide internet-based disease reporting system was established.",2011 Feb 18,"['Cao, Wu-Chun', 'de Vlas, Sake J.', 'Richardus, Jan Hendrik']",Infect Dis Rep,,,True
87e5c2fa3f9febab3992aa84f38ebdc324bd9738,PMC,"Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility",http://dx.doi.org/10.1016/S1473-3099(13)70304-9,PMC3895322,24239323,NO-CC CODE,"BACKGROUND: The novel Middle East respiratory syndrome coronavirus (MERS-CoV) had, as of Aug 8, 2013, caused 111 virologically confirmed or probable human cases of infection worldwide. We analysed epidemiological and genetic data to assess the extent of human infection, the performance of case detection, and the transmission potential of MERS-CoV with and without control measures. METHODS: We assembled a comprehensive database of all confirmed and probable cases from public sources and estimated the incubation period and generation time from case cluster data. Using data of numbers of visitors to the Middle East and their duration of stay, we estimated the number of symptomatic cases in the Middle East. We did independent analyses, looking at the growth in incident clusters, the growth in viral population, the reproduction number of cluster index cases, and cluster sizes to characterise the dynamical properties of the epidemic and the transmission scenario. FINDINGS: The estimated number of symptomatic cases up to Aug 8, 2013, is 940 (95% CI 290–2200), indicating that at least 62% of human symptomatic cases have not been detected. We find that the case-fatality ratio of primary cases detected via routine surveillance (74%; 95% CI 49–91) is biased upwards because of detection bias; the case-fatality ratio of secondary cases was 20% (7–42). Detection of milder cases (or clinical management) seemed to have improved in recent months. Analysis of human clusters indicated that chains of transmission were not self-sustaining when infection control was implemented, but that R in the absence of controls was in the range 0·8–1·3. Three independent data sources provide evidence that R cannot be much above 1, with an upper bound of 1·2–1·5. INTERPRETATION: By showing that a slowly growing epidemic is underway either in human beings or in an animal reservoir, quantification of uncertainty in transmissibility estimates, and provision of the first estimates of the scale of the epidemic and extent of case detection biases, we provide valuable information for more informed risk assessment. FUNDING: Medical Research Council, Bill & Melinda Gates Foundation, EU FP7, and National Institute of General Medical Sciences.",2014 Jan,"['Cauchemez, Simon', 'Fraser, Christophe', 'Van Kerkhove, Maria D', 'Donnelly, Christl A', 'Riley, Steven', 'Rambaut, Andrew', 'Enouf, Vincent', 'van der Werf, Sylvie', 'Ferguson, Neil M']",Lancet Infect Dis,,,True
169edebe1c7c37c530c58a25683bdae4cc4eb14e,PMC,Replicative Capacity of MERS Coronavirus in Livestock Cell Lines,http://dx.doi.org/10.3201/eid2002.131182,PMC3901466,24457147,NO-CC CODE,Replicative capacity of Middle East respiratory syndrome coronavirus (MERS-CoV) was assessed in cell lines derived from livestock and peridomestic small mammals on the Arabian Peninsula. Only cell lines originating from goats and camels showed efficient replication of MERS-CoV. These results provide direction in the search for the intermediate host of MERS-CoV.,2014 Feb,"['Eckerle, Isabella', 'Corman, Victor M.', 'Müller, Marcel A.', 'Lenk, Matthias', 'Ulrich, Rainer G.', 'Drosten, Christian']",Emerg Infect Dis,,,True
8e34a3230f0fc157b5d5ed998fa8792f0ecf3d0e,PMC,"Low-Incidence, High-Consequence Pathogens",http://dx.doi.org/10.3201/eid2002.131748,PMC3901478,24596949,NO-CC CODE,,2014 Feb,"['Belay, Ermias D.', 'Monroe, Stephan S.']",Emerg Infect Dis,,,True
917f664cddf8f82b6981fca23210ce68f7aad01d,PMC,"Genetic Characterization of Coronaviruses from Domestic Ferrets, Japan",http://dx.doi.org/10.3201/eid2002.130543,PMC3901494,24447852,NO-CC CODE,We detected ferret coronaviruses in 44 (55.7%) of 79 pet ferrets tested in Japan and classified the viruses into 2 genotypes on the basis of genotype-specific PCR. Our results show that 2 ferret coronaviruses that cause feline infectious peritonitis–like disease and epizootic catarrhal enteritis are enzootic among ferrets in Japan.,2014 Feb,"['Terada, Yutaka', 'Minami, Shohei', 'Noguchi, Keita', 'Mahmoud, Hassan Y.A.H.', 'Shimoda, Hiroshi', 'Mochizuki, Masami', 'Une, Yumi', 'Maeda, Ken']",Emerg Infect Dis,,,True
9be839381833cc5da620a0c6c25da09c3a0ea961,PMC,"Looking Back, Looking Forward",http://dx.doi.org/10.7453/gahmj.2014.001,PMC3921617,24753988,NO-CC CODE,,2014 Jan 1,"Riley, David",Glob Adv Health Med,,,True
eeaba0837e6425e745caef024c53670d335f0e02,PMC,"The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family",http://dx.doi.org/10.1007/s11033-014-3019-7,PMC3933739,24413991,NO-CC CODE,"Extracts of Anthemis hyalina (Ah), Nigella sativa (Ns) and peels of Citrus sinensis (Cs) have been used as folk medicine to fight antimicrobial diseases. To evaluate the effect of extracts of Ah, Ns and Cs on the replication of coronavirus (CoV) and on the expression of TRP genes during coronavirus infection, HeLa-CEACAM1a (HeLa-epithelial carcinoembryonic antigen-related cell adhesion molecule 1a) cells were inoculated with MHV-A59 (mouse hepatitis virus–A59) at moi of 30. 1/50 dilution of the extracts was found to be the safe active dose. ELISA kits were used to detect the human IL-8 levels. Total RNA was isolated from the infected cells and cDNA was synthesized. Fluidigm Dynamic Array nanofluidic chip 96.96 was used to analyze the mRNA expression of 21 TRP genes and two control genes. Data was analyzed using the BioMark digital array software. Determinations of relative gene expression values were carried out by using the 2(−∆∆Ct) method (normalized threshold cycle (Ct) value of sample minus normalized Ct value of control). TCID(50)/ml (tissue culture infectious dose that will produce cytopathic effect in 50 % of the inoculated tissue culture cells) was found for treatments to determine the viral loads. The inflammatory cytokine IL-8 level was found to increase for both 24 and 48 h time points following Ns extract treatment. TRPA1, TRPC4, TRPM6, TRPM7, TRPM8 and TRPV4 were the genes which expression levels changed significantly after Ah, Ns or Cs extract treatments. The virus load decreased when any of the Ah, Ns or Cs extracts was added to the CoV infected cells with Ah extract treatment leading to undetectable virus load for both 6 and 8hpi. Although all the extract treatments had an effect on IL-8 secretion, TRP gene expression and virus load after CoV infection, it was the Ah extract treatment that showed the biggest difference in virus load. Therefore Ah extract is the best candidate in our hands that contains potential treatment molecule(s). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11033-014-3019-7) contains supplementary material, which is available to authorized users.",2014 Jan 12,"['Ulasli, Mustafa', 'Gurses, Serdar A.', 'Bayraktar, Recep', 'Yumrutas, Onder', 'Oztuzcu, Serdar', 'Igci, Mehri', 'Igci, Yusuf Ziya', 'Cakmak, Ecir Ali', 'Arslan, Ahmet']",Mol Biol Rep,,,False
145f37b63789de6209b2d69b56ea22f8755d76f1,PMC,"The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family",http://dx.doi.org/10.1007/s11033-014-3019-7,PMC3933739,24413991,NO-CC CODE,"Extracts of Anthemis hyalina (Ah), Nigella sativa (Ns) and peels of Citrus sinensis (Cs) have been used as folk medicine to fight antimicrobial diseases. To evaluate the effect of extracts of Ah, Ns and Cs on the replication of coronavirus (CoV) and on the expression of TRP genes during coronavirus infection, HeLa-CEACAM1a (HeLa-epithelial carcinoembryonic antigen-related cell adhesion molecule 1a) cells were inoculated with MHV-A59 (mouse hepatitis virus–A59) at moi of 30. 1/50 dilution of the extracts was found to be the safe active dose. ELISA kits were used to detect the human IL-8 levels. Total RNA was isolated from the infected cells and cDNA was synthesized. Fluidigm Dynamic Array nanofluidic chip 96.96 was used to analyze the mRNA expression of 21 TRP genes and two control genes. Data was analyzed using the BioMark digital array software. Determinations of relative gene expression values were carried out by using the 2(−∆∆Ct) method (normalized threshold cycle (Ct) value of sample minus normalized Ct value of control). TCID(50)/ml (tissue culture infectious dose that will produce cytopathic effect in 50 % of the inoculated tissue culture cells) was found for treatments to determine the viral loads. The inflammatory cytokine IL-8 level was found to increase for both 24 and 48 h time points following Ns extract treatment. TRPA1, TRPC4, TRPM6, TRPM7, TRPM8 and TRPV4 were the genes which expression levels changed significantly after Ah, Ns or Cs extract treatments. The virus load decreased when any of the Ah, Ns or Cs extracts was added to the CoV infected cells with Ah extract treatment leading to undetectable virus load for both 6 and 8hpi. Although all the extract treatments had an effect on IL-8 secretion, TRP gene expression and virus load after CoV infection, it was the Ah extract treatment that showed the biggest difference in virus load. Therefore Ah extract is the best candidate in our hands that contains potential treatment molecule(s). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11033-014-3019-7) contains supplementary material, which is available to authorized users.",2014 Jan 12,"['Ulasli, Mustafa', 'Gurses, Serdar A.', 'Bayraktar, Recep', 'Yumrutas, Onder', 'Oztuzcu, Serdar', 'Igci, Mehri', 'Igci, Yusuf Ziya', 'Cakmak, Ecir Ali', 'Arslan, Ahmet']",Mol Biol Rep,,,True
881bb13e961f96f6d3ba6e0cd749126d56245bb8,PMC,"Influenza A(H1N1)pdm09 Virus Infection in Giant Pandas, China",http://dx.doi.org/10.3201/eid2003.131531,PMC3944863,24565026,NO-CC CODE,We confirmed infection with influenza A(H1N1)pdm09 in giant pandas in China during 2009 by using virus isolation and serologic analysis methods. This finding extends the host range of influenza viruses and indicates a need for increased surveillance for and control of influenza viruses among giant pandas.,2014 Mar,"['Li, Desheng', 'Zhu, Ling', 'Cui, Hengmin', 'Ling, Shanshan', 'Fan, Shengtao', 'Yu, Zhijun', 'Zhou, Yuancheng', 'Wang, Tiecheng', 'Qian, Jun', 'Xia, Xianzhu', 'Xu, Zhiwen', 'Gao, Yuwei', 'Wang, Chengdong']",Emerg Infect Dis,,,True
818caae91a81785b3f7de5d8c9ccdc18e0743872,PMC,"Influenza A(H1N1)pdm09 Virus Infection in Giant Pandas, China",http://dx.doi.org/10.3201/eid2003.131531,PMC3944863,24565026,NO-CC CODE,We confirmed infection with influenza A(H1N1)pdm09 in giant pandas in China during 2009 by using virus isolation and serologic analysis methods. This finding extends the host range of influenza viruses and indicates a need for increased surveillance for and control of influenza viruses among giant pandas.,2014 Mar,"['Li, Desheng', 'Zhu, Ling', 'Cui, Hengmin', 'Ling, Shanshan', 'Fan, Shengtao', 'Yu, Zhijun', 'Zhou, Yuancheng', 'Wang, Tiecheng', 'Qian, Jun', 'Xia, Xianzhu', 'Xu, Zhiwen', 'Gao, Yuwei', 'Wang, Chengdong']",Emerg Infect Dis,,,False
ac6ab25f83e79fc2c1794b69c8bbfe0616f527ad,PMC,"Hendra Virus Vaccine, a One Health Approach to Protecting Horse, Human, and Environmental Health",http://dx.doi.org/10.3201/eid2003.131159,PMC3944873,24572697,NO-CC CODE,"In recent years, the emergence of several highly pathogenic zoonotic diseases in humans has led to a renewed emphasis on the interconnectedness of human, animal, and environmental health, otherwise known as One Health. For example, Hendra virus (HeV), a zoonotic paramyxovirus, was discovered in 1994, and since then, infections have occurred in 7 humans, each of whom had a strong epidemiologic link to similarly affected horses. As a consequence of these outbreaks, eradication of bat populations was discussed, despite their crucial environmental roles in pollination and reduction of the insect population. We describe the development and evaluation of a vaccine for horses with the potential for breaking the chain of HeV transmission from bats to horses to humans, thereby protecting horse, human, and environmental health. The HeV vaccine for horses is a key example of a One Health approach to the control of human disease.",2014 Mar,"['Middleton, Deborah', 'Pallister, Jackie', 'Klein, Reuben', 'Feng, Yan-Ru', 'Haining, Jessica', 'Arkinstall, Rachel', 'Frazer, Leah', 'Huang, Jin-An', 'Edwards, Nigel', 'Wareing, Mark', 'Elhay, Martin', 'Hashmi, Zia', 'Bingham, John', 'Yamada, Manabu', 'Johnson, Dayna', 'White, John', 'Foord, Adam', 'Heine, Hans G.', 'Marsh, Glenn A.', 'Broder, Christopher C.', 'Wang, Lin-Fa']",Emerg Infect Dis,,,True
7a054783434b19b3fb546990d25b735659fc851a,PMC,High-Affinity Recognition of HIV-1 Frameshift-Stimulating RNA Alters Frameshifting in Vitro and Interferes with HIV-1 Infectivity,http://dx.doi.org/10.1021/jm401438g,PMC3954503,24387306,NO-CC CODE,"[Image: see text] The life cycle of the human immunodeficiency virus type 1 (HIV-1) has an absolute requirement for ribosomal frameshifting during protein translation in order to produce the polyprotein precursor of the viral enzymes. While an RNA stem-loop structure (the “HIV-1 Frameshift Stimulating Signal”, or HIV-1 FSS) controls the frameshift efficiency and has been hypothesized as an attractive therapeutic target, developing compounds that selectively bind this RNA and interfere with HIV-1 replication has proven challenging. Building on our prior discovery of a “hit” molecule able to bind this stem-loop, we now report the development of compounds displaying high affinity for the HIV-1 FSS. These compounds are able to enhance frameshifting more than 50% in a dual-luciferase assay in human embryonic kidney cells, and they strongly inhibit the infectivity of pseudotyped HIV-1 virions.",2014 Feb 13,"['Ofori, Leslie\nO.', 'Hilimire, Thomas A.', 'Bennett, Ryan P.', 'Brown, Nathaniel\nW.', 'Smith, Harold C.', 'Miller, Benjamin L.']",J Med Chem,,,True
b345fe36029c6ccebee177f8635ea0a5ab5f0141,PMC,High-Affinity Recognition of HIV-1 Frameshift-Stimulating RNA Alters Frameshifting in Vitro and Interferes with HIV-1 Infectivity,http://dx.doi.org/10.1021/jm401438g,PMC3954503,24387306,NO-CC CODE,"[Image: see text] The life cycle of the human immunodeficiency virus type 1 (HIV-1) has an absolute requirement for ribosomal frameshifting during protein translation in order to produce the polyprotein precursor of the viral enzymes. While an RNA stem-loop structure (the “HIV-1 Frameshift Stimulating Signal”, or HIV-1 FSS) controls the frameshift efficiency and has been hypothesized as an attractive therapeutic target, developing compounds that selectively bind this RNA and interfere with HIV-1 replication has proven challenging. Building on our prior discovery of a “hit” molecule able to bind this stem-loop, we now report the development of compounds displaying high affinity for the HIV-1 FSS. These compounds are able to enhance frameshifting more than 50% in a dual-luciferase assay in human embryonic kidney cells, and they strongly inhibit the infectivity of pseudotyped HIV-1 virions.",2014 Feb 13,"['Ofori, Leslie\nO.', 'Hilimire, Thomas A.', 'Bennett, Ryan P.', 'Brown, Nathaniel\nW.', 'Smith, Harold C.', 'Miller, Benjamin L.']",J Med Chem,,,False
e0737ee93afe7b0bf06b1e3f9adf21d541dd10f0,PMC,Protective Effects of Long Pentraxin PTX3 on Lung Injury in a Severe Acute Respiratory Syndrome Model in Mice,http://dx.doi.org/10.1038/labinvest.2012.92,PMC3955193,22732935,NO-CC CODE,"The outbreak of severe acute respiratory syndrome (SARS) in 2003 reinforces the potential of lethal pandemics of respiratory viral infection s. The underlying mechanisms of SARS are still largely undefined. Long pentraxin PTX3, a humoral mediator of innate immunity, has been reported to have anti-viral effects. We examined the role of PTX3 in Coronavirus murine hepatitis virus strain 1 (MHV-1)-induced acute lung injury, a previously reported animal model for SARS. PTX3 deficient mice (129/SvEv/C57BL6/J) and their wild type littermates were intranasally infected MHV-1. These mice were also treated with recombinant PTX3. Effects of PTX3 on viral binding and infectivity were determined in vitro. Cytokine expression, severity of lung injury, leukocyte infiltration and inflammatory responses were examined in vivo. In PTX3wild type mice, MHV -1 induced PTX3 expression in the lung and serum in a time dependent manner. MHV-1 infection led to acute lung injury with greater severity in PTX3 deficient mice than that in wild type mice. PTX3 deficiency enhanced early infiltration of neutrophils and macrophages in the lung. PTX3 bound to MHV-1 and MHV-3 and reduced MHV-1 infectivity in vitro. Administration of recombinant PTX3 significantly accelerated viral clearance in the lung; attenuated MHV-1 induced lung injury, and reduced early neutrophil influx and elevation of inflammatory mediators in the lung. Results from this study indicate a protective role of PTX3 in coronaviral infection -induced acute lung injury.",2012 Sep 25,"['Han, Bing', 'Ma, Xuezhong', 'Zhang, Jianhua', 'Zhang, Yu', 'Bai, Xiaohui', 'Hwang, David M.', 'Keshavjee, Shaf', 'Levy, Gary', 'McGilvray, Ian', 'Liu, Mingyao']",Lab Invest,,,True
2e62dd52f92a91d9fd39e146fcadc9208e0e9535,PMC,Protective Effects of Long Pentraxin PTX3 on Lung Injury in a Severe Acute Respiratory Syndrome Model in Mice,http://dx.doi.org/10.1038/labinvest.2012.92,PMC3955193,22732935,NO-CC CODE,"The outbreak of severe acute respiratory syndrome (SARS) in 2003 reinforces the potential of lethal pandemics of respiratory viral infection s. The underlying mechanisms of SARS are still largely undefined. Long pentraxin PTX3, a humoral mediator of innate immunity, has been reported to have anti-viral effects. We examined the role of PTX3 in Coronavirus murine hepatitis virus strain 1 (MHV-1)-induced acute lung injury, a previously reported animal model for SARS. PTX3 deficient mice (129/SvEv/C57BL6/J) and their wild type littermates were intranasally infected MHV-1. These mice were also treated with recombinant PTX3. Effects of PTX3 on viral binding and infectivity were determined in vitro. Cytokine expression, severity of lung injury, leukocyte infiltration and inflammatory responses were examined in vivo. In PTX3wild type mice, MHV -1 induced PTX3 expression in the lung and serum in a time dependent manner. MHV-1 infection led to acute lung injury with greater severity in PTX3 deficient mice than that in wild type mice. PTX3 deficiency enhanced early infiltration of neutrophils and macrophages in the lung. PTX3 bound to MHV-1 and MHV-3 and reduced MHV-1 infectivity in vitro. Administration of recombinant PTX3 significantly accelerated viral clearance in the lung; attenuated MHV-1 induced lung injury, and reduced early neutrophil influx and elevation of inflammatory mediators in the lung. Results from this study indicate a protective role of PTX3 in coronaviral infection -induced acute lung injury.",2012 Sep 25,"['Han, Bing', 'Ma, Xuezhong', 'Zhang, Jianhua', 'Zhang, Yu', 'Bai, Xiaohui', 'Hwang, David M.', 'Keshavjee, Shaf', 'Levy, Gary', 'McGilvray, Ian', 'Liu, Mingyao']",Lab Invest,,,False
13828eaedcbd1d65cf6384ed2e74b77d9e931c42,PMC,Protective Effects of Long Pentraxin PTX3 on Lung Injury in a Severe Acute Respiratory Syndrome Model in Mice,http://dx.doi.org/10.1038/labinvest.2012.92,PMC3955193,22732935,NO-CC CODE,"The outbreak of severe acute respiratory syndrome (SARS) in 2003 reinforces the potential of lethal pandemics of respiratory viral infection s. The underlying mechanisms of SARS are still largely undefined. Long pentraxin PTX3, a humoral mediator of innate immunity, has been reported to have anti-viral effects. We examined the role of PTX3 in Coronavirus murine hepatitis virus strain 1 (MHV-1)-induced acute lung injury, a previously reported animal model for SARS. PTX3 deficient mice (129/SvEv/C57BL6/J) and their wild type littermates were intranasally infected MHV-1. These mice were also treated with recombinant PTX3. Effects of PTX3 on viral binding and infectivity were determined in vitro. Cytokine expression, severity of lung injury, leukocyte infiltration and inflammatory responses were examined in vivo. In PTX3wild type mice, MHV -1 induced PTX3 expression in the lung and serum in a time dependent manner. MHV-1 infection led to acute lung injury with greater severity in PTX3 deficient mice than that in wild type mice. PTX3 deficiency enhanced early infiltration of neutrophils and macrophages in the lung. PTX3 bound to MHV-1 and MHV-3 and reduced MHV-1 infectivity in vitro. Administration of recombinant PTX3 significantly accelerated viral clearance in the lung; attenuated MHV-1 induced lung injury, and reduced early neutrophil influx and elevation of inflammatory mediators in the lung. Results from this study indicate a protective role of PTX3 in coronaviral infection -induced acute lung injury.",2012 Sep 25,"['Han, Bing', 'Ma, Xuezhong', 'Zhang, Jianhua', 'Zhang, Yu', 'Bai, Xiaohui', 'Hwang, David M.', 'Keshavjee, Shaf', 'Levy, Gary', 'McGilvray, Ian', 'Liu, Mingyao']",Lab Invest,,,False
8ccaf50414e8f530aaa405630c4e477d377d09ce,PMC,Complete Genome of Hepatitis E Virus from Laboratory Ferrets,http://dx.doi.org/10.3201/eid2004.131815,PMC3966362,24655541,NO-CC CODE,"The complete genome of hepatitis E virus (HEV) from laboratory ferrets imported from the United States was identified. This virus shared only 82.4%–82.5% nt sequence identities with strains from the Netherlands, which indicated that the ferret HEV genome is genetically diverse. Some laboratory ferrets were contaminated with HEV.",2014 Apr,"['Li, Tian-Cheng', 'Yang, Tingting', 'Ami, Yasushi', 'Suzaki, Yuriko', 'Shirakura, Masayuki', 'Kishida, Noriko', 'Asanuma, Hideki', 'Takeda, Naokazu', 'Takaji, Wakita']",Emerg Infect Dis,,,True
31ff32abd2da30cf9a0ed4414fb83e19eb874314,PMC,Truth in the Details,http://dx.doi.org/10.3201/eid2004.AC2004,PMC3966375,,NO-CC CODE,,2014 Apr,"['Bloom, Sharon', 'Weeks, Emily M.']",Emerg Infect Dis,,,True
9d9ad4fc953115d139ae6bad7522c4e685022065,PMC,"Novel Betacoronavirus in Dromedaries of the Middle East, 2013",http://dx.doi.org/10.3201/eid2004.131769,PMC3966378,24655427,NO-CC CODE,"In 2013, a novel betacoronavirus was identified in fecal samples from dromedaries in Dubai, United Arab Emirates. Antibodies against the recombinant nucleocapsid protein of the virus, which we named dromedary camel coronavirus (DcCoV) UAE-HKU23, were detected in 52% of 59 dromedary serum samples tested. In an analysis of 3 complete DcCoV UAE-HKU23 genomes, we identified the virus as a betacoronavirus in lineage A1. The DcCoV UAE-HKU23 genome has G+C contents; a general preference for G/C in the third position of codons; a cleavage site for spike protein; and a membrane protein of similar length to that of other betacoronavirus A1 members, to which DcCoV UAE-HKU23 is phylogenetically closely related. Along with this coronavirus, viruses of at least 8 other families have been found to infect camels. Because camels have a close association with humans, continuous surveillance should be conducted to understand the potential for virus emergence in camels and for virus transmission to humans.",2014 Apr,"['Woo, Patrick C.Y.', 'Lau, Susanna K.P.', 'Wernery, Ulrich', 'Wong, Emily Y.M.', 'Tsang, Alan K.L.', 'Johnson, Bobby', 'Yip, Cyril C.Y.', 'Lau, Candy C.Y.', 'Sivakumar, Saritha', 'Cai, Jian-Piao', 'Fan, Rachel Y.Y.', 'Chan, Kwok-Hung', 'Mareena, Ringu', 'Yuen, Kwok-Yung']",Emerg Infect Dis,,,True
e4f137f6a18bb08198bd2227d293e25090a12a24,PMC,"Novel Betacoronavirus in Dromedaries of the Middle East, 2013",http://dx.doi.org/10.3201/eid2004.131769,PMC3966378,24655427,NO-CC CODE,"In 2013, a novel betacoronavirus was identified in fecal samples from dromedaries in Dubai, United Arab Emirates. Antibodies against the recombinant nucleocapsid protein of the virus, which we named dromedary camel coronavirus (DcCoV) UAE-HKU23, were detected in 52% of 59 dromedary serum samples tested. In an analysis of 3 complete DcCoV UAE-HKU23 genomes, we identified the virus as a betacoronavirus in lineage A1. The DcCoV UAE-HKU23 genome has G+C contents; a general preference for G/C in the third position of codons; a cleavage site for spike protein; and a membrane protein of similar length to that of other betacoronavirus A1 members, to which DcCoV UAE-HKU23 is phylogenetically closely related. Along with this coronavirus, viruses of at least 8 other families have been found to infect camels. Because camels have a close association with humans, continuous surveillance should be conducted to understand the potential for virus emergence in camels and for virus transmission to humans.",2014 Apr,"['Woo, Patrick C.Y.', 'Lau, Susanna K.P.', 'Wernery, Ulrich', 'Wong, Emily Y.M.', 'Tsang, Alan K.L.', 'Johnson, Bobby', 'Yip, Cyril C.Y.', 'Lau, Candy C.Y.', 'Sivakumar, Saritha', 'Cai, Jian-Piao', 'Fan, Rachel Y.Y.', 'Chan, Kwok-Hung', 'Mareena, Ringu', 'Yuen, Kwok-Yung']",Emerg Infect Dis,,,False
5b418c0fc9be9eb87329aae74de81b3270e3603d,PMC,"Antibodies against MERS Coronavirus in Dromedary Camels, United Arab Emirates, 2003 and 2013",http://dx.doi.org/10.3201/eid2004.131746,PMC3966379,24655412,NO-CC CODE,"Middle East respiratory syndrome coronavirus (MERS-CoV) has caused an ongoing outbreak of severe acute respiratory tract infection in humans in the Arabian Peninsula since 2012. Dromedary camels have been implicated as possible viral reservoirs. We used serologic assays to analyze 651 dromedary camel serum samples from the United Arab Emirates; 151 of 651 samples were obtained in 2003, well before onset of the current epidemic, and 500 serum samples were obtained in 2013. Recombinant spike protein–specific immunofluorescence and virus neutralization tests enabled clear discrimination between MERS-CoV and bovine CoV infections. Most (632/651, 97.1%) camels had antibodies against MERS-CoV. This result included all 151 serum samples obtained in 2003. Most (389/651, 59.8%) serum samples had MERS-CoV–neutralizing antibody titers >1,280. Dromedary camels from the United Arab Emirates were infected at high rates with MERS-CoV or a closely related, probably conspecific, virus long before the first human MERS cases.",2014 Apr,"['Meyer, Benjamin', 'Müller, Marcel A.', 'Corman, Victor M.', 'Reusken, Chantal B.E.M.', 'Ritz, Daniel', 'Godeke, Gert-Jan', 'Lattwein, Erik', 'Kallies, Stephan', 'Siemens, Artem', 'van Beek, Janko', 'Drexler, Jan F.', 'Muth, Doreen', 'Bosch, Berend-Jan', 'Wernery, Ulrich', 'Koopmans, Marion P.G.', 'Wernery, Renate', 'Drosten, Christian']",Emerg Infect Dis,,,True
9241e0b97dce927be4592622e554fe81af5bfb2f,PMC,Lack of MERS Coronavirus but Prevalence of Influenza Virus in French Pilgrims after 2013 Hajj,http://dx.doi.org/10.3201/eid2004.131708,PMC3966380,24656283,NO-CC CODE,,2014 Apr,"['Gautret, Philippe', 'Charrel, Rémi', 'Benkouiten, Samir', 'Belhouchat, Khadidja', 'Nougairede, Antoine', 'Drali, Tassadit', 'Salez, Nicolas', 'Memish, Ziad A.', 'al Masri, Malak', 'Lagier, Jean-Christophe', 'Million, Matthieu', 'Raoult, Didier', 'Brouqui, Philippe', 'Parola, Philippe']",Emerg Infect Dis,,,True
36d93efb83871f3d6d3b92605ae47f5a9c182ca2,PMC,"New Alphacoronavirus in Mystacina tuberculata Bats, New Zealand",http://dx.doi.org/10.3201/eid2004.131441,PMC3966383,24656060,NO-CC CODE,"Because of recent interest in bats as reservoirs of emerging diseases, we investigated the presence of viruses in Mystacina tuberculata bats in New Zealand. A novel alphacoronavirus sequence was detected in guano from roosts of M. tuberculata bats in pristine indigenous forest on a remote offshore island (Codfish Island).",2014 Apr,"['Hall, Richard J.', 'Wang, Jing', 'Peacey, Matthew', 'Moore, Nicole E.', 'McInnes, Kate', 'Tompkins, Daniel M.']",Emerg Infect Dis,,,True
3c020dec5b062a2b10f71b7a3030ac306a093cd5,PMC,Pathology of US Porcine Epidemic Diarrhea Virus Strain PC21A in Gnotobiotic Pigs,http://dx.doi.org/10.3201/eid2004.131685,PMC3966387,24795932,NO-CC CODE,"To understand the progression of porcine epidemic diarrhea virus infection, we inoculated gnotobiotic pigs with a newly emerged US strain, PC21A, of the virus. At 24–48 hours postinoculation, the pigs exhibited severe diarrhea and vomiting, fecal shedding, viremia, and severe atrophic enteritis. These findings confirm that strain PC21A is highly enteropathogenic.",2014 Apr,"['Jung, Kwonil', 'Wang, Qiuhong', 'Scheuer, Kelly A.', 'Lu, Zhongyan', 'Zhang, Yan', 'Saif, Linda J.']",Emerg Infect Dis,,,True
f2e0d9212887c0032b1887f34ee3b3042510d7f9,PMC,"Contact Investigation for Imported Case of Middle East Respiratory Syndrome, Germany",http://dx.doi.org/10.3201/eid2004.131375,PMC3966395,24655721,NO-CC CODE,"On March 19, 2013, a patient from United Arab Emirates who had severe respiratory infection was transferred to a hospital in Germany, 11 days after symptom onset. Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) was suspected on March 21 and confirmed on March 23; the patient, who had contact with an ill camel shortly before symptom onset, died on March 26. A contact investigation was initiated to identify possible person-to-person transmission and assess infection control measures. Of 83 identified contacts, 81 were available for follow-up. Ten contacts experienced mild symptoms, but test results for respiratory and serum samples were negative for MERS-CoV. Serologic testing was done for 53 (75%) of 71 nonsymptomatic contacts; all results were negative. Among contacts, the use of FFP2/FFP3 face masks during aerosol exposure was more frequent after MERS-CoV infection was suspected than before. Infection control measures may have prevented nosocomial transmission of the virus.",2014 Apr,"['Reuss, Annicka', 'Litterst, Annette', 'Drosten, Christian', 'Seilmaier, Michael', 'Böhmer, Merle', 'Graf, Petra', 'Gold, Hermann', 'Wendtner, Clemens-Martin', 'Zanuzdana, Arina', 'Schaade, Lars', 'Haas, Walter', 'Buchholz, Udo']",Emerg Infect Dis,,,True
5baa1d21e6334a0af38c31d852992e7e6ad2402c,PMC,A new unconventional HLA-A2-restricted epitope from HBV core protein elicits antiviral cytotoxic T lymphocytes,http://dx.doi.org/10.1007/s13238-014-0041-4,PMC3978166,24659387,NO-CC CODE,"Cytotoxic T cells (CTLs) play a key role in the control of Hepatitis B virus (HBV) infection and viral clearance. However, most of identified CTL epitopes are derived from HBV of genotypes A and D, and few have been defined in virus of genotypes B and C which are more prevalent in Asia. As HBV core protein (HBc) is the most conservative and immunogenic component, in this study we used an overlapping 9-mer peptide pool covering HBc to screen and identify specific CTL epitopes. An unconventional HLA-A2-restricted epitope HBc141–149 was discovered and structurally characterized by crystallization analysis. The immunogenicity and anti-HBV activity were further determined in HBV and HLA-A2 transgenic mice. Finally, we show that mutations in HBc141–149 epitope are associated with viral parameters and disease progression in HBV infected patients. Our data therefore provide insights into the structure characteristics of this unconventional epitope binding to MHC-I molecules, as well as epitope specific CTL activity that orchestrate T cell response and immune evasion in HBV infected patients.",2014 Apr 22,"['Sun, Lu', 'Zhang, Yu', 'Zhao, Bao', 'Deng, Mengmeng', 'Liu, Jun', 'Li, Xin', 'Hou, Junwei', 'Gui, Mingming', 'Zhang, Shuijun', 'Li, Xiaodong', 'Gao, George F.', 'Meng, Songdong']",Protein Cell,,,True
8cbc79e63c08258edef9ed362498b779a592977a,PMC,Metagenomics for pathogen detection in public health,http://dx.doi.org/10.1186/gm485,PMC3978900,24050114,NO-CC CODE,"Traditional pathogen detection methods in public health infectious disease surveillance rely upon the identification of agents that are already known to be associated with a particular clinical syndrome. The emerging field of metagenomics has the potential to revolutionize pathogen detection in public health laboratories by allowing the simultaneous detection of all microorganisms in a clinical sample, without a priori knowledge of their identities, through the use of next-generation DNA sequencing. A single metagenomics analysis has the potential to detect rare and novel pathogens, and to uncover the role of dysbiotic microbiomes in infectious and chronic human disease. Making use of advances in sequencing platforms and bioinformatics tools, recent studies have shown that metagenomics can even determine the whole-genome sequences of pathogens, allowing inferences about antibiotic resistance, virulence, evolution and transmission to be made. We are entering an era in which more novel infectious diseases will be identified through metagenomics-based methods than through traditional laboratory methods. The impetus is now on public health laboratories to integrate metagenomics techniques into their diagnostic arsenals.",2013 Sep 20,"['Miller, Ruth R', 'Montoya, Vincent', 'Gardy, Jennifer L', 'Patrick, David M', 'Tang, Patrick']",Genome Med,,,True
b75374ebf027be698e5ce4e721a4840dc4384240,PMC,IN VITRO ASSESSMENT OF THE BIOLOGIC ACTIVITY OF INTERFERON BETA FORMULATIONS USED FOR THE TREATMENT OF RELAPSING MULTIPLE SCLEROSIS,http://dx.doi.org/10.1080/15321819.2013.848815,PMC3979447,24654824,NO-CC CODE,"□ A new formulation (NF) of subcutaneous (sc) interferon (IFN) β-1a was developed in an attempt to improve injection tolerability and immunogenicity. We compared antiviral and IFNβ-stimulated gene (ISG) activities of IFNβ-1a sc NF with IFNβ-1a sc original formulation and IFNβ-1b sc. When equivalent unit amounts were compared, the IFNβ formulations demonstrated similar antiviral activity and induced similar levels of ISG mRNA. However, on a weight basis (ng/mL), significantly more IFNβ-1b sc was needed to equal the antiviral activity of either IFNβ-1a sc formulation, and both IFNβ-1a sc formulations induced significantly higher levels of ISG mRNA than IFNβ-1b sc.",2014 Jul 21,"['Scagnolari, Carolina', 'Selvaggi, Carla', 'Di Biase, Emilia', 'Fraulo, Maurizio', 'Dangond, Fernando', 'Antonelli, Guido']",J Immunoassay Immunochem,,,True
f45b20a7cfdc6f8300d934c4599b089671605884,PMC,Mouse Development From Oocyte to Stem Cells,http://dx.doi.org/10.4081/ejh.2014.2369,PMC3980216,,NO-CC CODE,,2014 Feb 19,"Monti, Manuela",Eur J Histochem,,,False
746397a8fa84468dcf0a9e8465d7cc090441f058,PMC,Lobar flexible fiberoptic lung lavage: therapeutic benefit in severe respiratory failure in pulmonary alveolar proteinosis and influenza A H1N1 pneumonia,http://dx.doi.org/10.4081/cp.2011.e53,PMC3981374,24765314,NO-CC CODE,"Lobar fiberoptic lung lavage is a well-known procedure used in primary pulmonary alveolar proteinosis (PAP); the use of this procedure has increased in the recent years. This procedure has also been used in other pulmonary diseases such as desquamative interstitial pneumonia with good results. We describe a case of extremely severe respiratory failure due to concurrence of PAP and Influenza A H1N1 virus pneumonia which resolved with the help of this procedure. The patient, a 41-year-old woman, needed less mechanical ventilation after undergoing lobar fiberoptic bronchoscopic lavage. Moreover, a rapid and progressive improvement in the computed tomography of the lungs was observed. Flexibile fiberoptic bronchoscopic lobar lavage is a simple, safe procedure used not only in milder disease, but also in particular severe cases in which the physiological derangement of whole lung lavage would not be tolerated by patient or when extra-corporeal membrane oxygenation is not available.",2011 Jul 1,"['Nicolini, Antonello', 'Barlascini, Cornelius']",Clin Pract,,,True
2f3883fe9db3bd0858a68a14233e076dd59e3e4f,PMC,Structural Basis for the Identification of the N-Terminal Domain of Coronavirus Nucleocapsid Protein as an Antiviral Target,http://dx.doi.org/10.1021/jm500089r,PMC3983370,24564608,NO-CC CODE,"[Image: see text] Coronaviruses (CoVs) cause numerous diseases, including Middle East respiratory syndrome and severe acute respiratory syndrome, generating significant health-related and economic consequences. CoVs encode the nucleocapsid (N) protein, a major structural protein that plays multiple roles in the virus replication cycle and forms a ribonucleoprotein complex with the viral RNA through the N protein’s N-terminal domain (N-NTD). Using human CoV-OC43 (HCoV-OC43) as a model for CoV, we present the 3D structure of HCoV-OC43 N-NTD complexed with ribonucleoside 5′-monophosphates to identify a distinct ribonucleotide-binding pocket. By targeting this pocket, we identified and developed a new coronavirus N protein inhibitor, N-(6-oxo-5,6-dihydrophenanthridin-2-yl)(N,N-dimethylamino)acetamide hydrochloride (PJ34), using virtual screening; this inhibitor reduced the N protein’s RNA-binding affinity and hindered viral replication. We also determined the crystal structure of the N-NTD–PJ34 complex. On the basis of these findings, we propose guidelines for developing new N protein-based antiviral agents that target CoVs.",2014 Mar 27,"['Lin, Shing-Yen', 'Liu, Chia-Ling', 'Chang, Yu-Ming', 'Zhao, Jincun', 'Perlman, Stanley', 'Hou, Ming-Hon']",J Med Chem,,,True
fd193c4454e959a01d62a4a31358b9aca9422bba,PMC,Structural Basis for the Identification of the N-Terminal Domain of Coronavirus Nucleocapsid Protein as an Antiviral Target,http://dx.doi.org/10.1021/jm500089r,PMC3983370,24564608,NO-CC CODE,"[Image: see text] Coronaviruses (CoVs) cause numerous diseases, including Middle East respiratory syndrome and severe acute respiratory syndrome, generating significant health-related and economic consequences. CoVs encode the nucleocapsid (N) protein, a major structural protein that plays multiple roles in the virus replication cycle and forms a ribonucleoprotein complex with the viral RNA through the N protein’s N-terminal domain (N-NTD). Using human CoV-OC43 (HCoV-OC43) as a model for CoV, we present the 3D structure of HCoV-OC43 N-NTD complexed with ribonucleoside 5′-monophosphates to identify a distinct ribonucleotide-binding pocket. By targeting this pocket, we identified and developed a new coronavirus N protein inhibitor, N-(6-oxo-5,6-dihydrophenanthridin-2-yl)(N,N-dimethylamino)acetamide hydrochloride (PJ34), using virtual screening; this inhibitor reduced the N protein’s RNA-binding affinity and hindered viral replication. We also determined the crystal structure of the N-NTD–PJ34 complex. On the basis of these findings, we propose guidelines for developing new N protein-based antiviral agents that target CoVs.",2014 Mar 27,"['Lin, Shing-Yen', 'Liu, Chia-Ling', 'Chang, Yu-Ming', 'Zhao, Jincun', 'Perlman, Stanley', 'Hou, Ming-Hon']",J Med Chem,,,False
84ba11845e71831d66c57966eb03e3190057fee7,PMC,X-ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain-like Proteases,http://dx.doi.org/10.1021/jm401712t,PMC3983375,24568342,NO-CC CODE,"[Image: see text] Structure-guided design was used to generate a series of noncovalent inhibitors with nanomolar potency against the papain-like protease (PLpro) from the SARS coronavirus (CoV). A number of inhibitors exhibit antiviral activity against SARS-CoV infected Vero E6 cells and broadened specificity toward the homologous PLP2 enzyme from the human coronavirus NL63. Selectivity and cytotoxicity studies established a more than 100-fold preference for the coronaviral enzyme over homologous human deubiquitinating enzymes (DUBs), and no significant cytotoxicity in Vero E6 and HEK293 cell lines is observed. X-ray structural analyses of inhibitor-bound crystal structures revealed subtle differences between binding modes of the initial benzodioxolane lead (15g) and the most potent analogues 3k and 3j, featuring a monofluoro substitution at para and meta positions of the benzyl ring, respectively. Finally, the less lipophilic bis(amide) 3e and methoxypyridine 5c exhibit significantly improved metabolic stability and are viable candidates for advancing to in vivo studies.",2014 Mar 27,"['Báez-Santos, Yahira\nM.', 'Barraza, Scott J.', 'Wilson, Michael W.', 'Agius, Michael P.', 'Mielech, Anna M.', 'Davis, Nicole M.', 'Baker, Susan C.', 'Larsen, Scott D.', 'Mesecar, Andrew D.']",J Med Chem,,,True
374834808ed55e895c9da2d0687b007b84972897,PMC,Injection Route and TLR9 Agonist Addition Significantly Impact Heroin Vaccine Efficacy,http://dx.doi.org/10.1021/mp400631w,PMC3993894,24517171,NO-CC CODE,"[Image: see text] Active immunization is an effective means of blocking the pharmacodynamic effects of drugs and holds promise as a treatment for heroin addiction. Previously, we demonstrated the efficacy of our first-generation vaccine in blocking heroin self-administration in rats, however, many vaccine components can be modified to further improve performance. Herein we examine the effects of varying heroin vaccine injection route and adjuvant formulation. Mice immunized via subcutaneous (sc) injection exhibited inferior anti-heroin titers compared to intraperitoneal (ip) and sc/ip coadministration injection routes. Addition of TLR9 agonist cytosine-guanine oligodeoxynucleotide 1826 (CpG ODN 1826) to the original alum adjuvant elicited superior antibody titers and opioid affinities compared to alum alone. To thoroughly assess vaccine efficacy, full dose–response curves were generated for heroin-induced analgesia in both hot plate and tail immersion tests. Mice treated with CpG ODN 1826 exhibited greatly shifted dose–response curves (10–13-fold vs unvaccinated controls) while non-CpG ODN vaccine groups did not exhibit the same robust effect (2–7-fold shift for ip and combo, 2–3-fold shift for sc). Our results suggest that CpG ODN 1826 is a highly potent adjuvant, and injection routes should be considered for development of small molecule–protein conjugate vaccines. Lastly, this study has established a new standard for assessing drugs of abuse vaccines, wherein a full dose–response curve should be performed in an appropriate behavioral task.",2014 Mar 3,"['Bremer, Paul T.', 'Schlosburg, Joel E.', 'Lively, Jenny M.', 'Janda, Kim D.']",Mol Pharm,,,True
2f787a3576169eb58da0ec737994385190b024d6,PMC,Injection Route and TLR9 Agonist Addition Significantly Impact Heroin Vaccine Efficacy,http://dx.doi.org/10.1021/mp400631w,PMC3993894,24517171,NO-CC CODE,"[Image: see text] Active immunization is an effective means of blocking the pharmacodynamic effects of drugs and holds promise as a treatment for heroin addiction. Previously, we demonstrated the efficacy of our first-generation vaccine in blocking heroin self-administration in rats, however, many vaccine components can be modified to further improve performance. Herein we examine the effects of varying heroin vaccine injection route and adjuvant formulation. Mice immunized via subcutaneous (sc) injection exhibited inferior anti-heroin titers compared to intraperitoneal (ip) and sc/ip coadministration injection routes. Addition of TLR9 agonist cytosine-guanine oligodeoxynucleotide 1826 (CpG ODN 1826) to the original alum adjuvant elicited superior antibody titers and opioid affinities compared to alum alone. To thoroughly assess vaccine efficacy, full dose–response curves were generated for heroin-induced analgesia in both hot plate and tail immersion tests. Mice treated with CpG ODN 1826 exhibited greatly shifted dose–response curves (10–13-fold vs unvaccinated controls) while non-CpG ODN vaccine groups did not exhibit the same robust effect (2–7-fold shift for ip and combo, 2–3-fold shift for sc). Our results suggest that CpG ODN 1826 is a highly potent adjuvant, and injection routes should be considered for development of small molecule–protein conjugate vaccines. Lastly, this study has established a new standard for assessing drugs of abuse vaccines, wherein a full dose–response curve should be performed in an appropriate behavioral task.",2014 Mar 3,"['Bremer, Paul T.', 'Schlosburg, Joel E.', 'Lively, Jenny M.', 'Janda, Kim D.']",Mol Pharm,,,False
97a3bb18c51244482cb68d5565389266a0cb7098,PMC,SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex,http://dx.doi.org/10.1007/s13238-014-0026-3,PMC3996160,24622840,NO-CC CODE,"SARS coronavirus (SARS-CoV) develops an antagonistic mechanism by which to evade the antiviral activities of interferon (IFN). Previous studies suggested that SARS-CoV papain-like protease (PLpro) inhibits activation of the IRF3 pathway, which would normally elicit a robust IFN response, but the mechanism(s) used by SARS PLpro to inhibit activation of the IRF3 pathway is not fully known. In this study, we uncovered a novel mechanism that may explain how SARS PLpro efficiently inhibits activation of the IRF3 pathway. We found that expression of the membrane-anchored PLpro domain (PLpro-TM) from SARS-CoV inhibits STING/TBK1/IKKε-mediated activation of type I IFNs and disrupts the phosphorylation and dimerization of IRF3, which are activated by STING and TBK1. Meanwhile, we showed that PLpro-TM physically interacts with TRAF3, TBK1, IKKε, STING, and IRF3, the key components that assemble the STING-TRAF3-TBK1 complex for activation of IFN expression. However, the interaction between the components in STING-TRAF3-TBK1 complex is disrupted by PLpro-TM. Furthermore, SARS PLpro-TM reduces the levels of ubiquitinated forms of RIG-I, STING, TRAF3, TBK1, and IRF3 in the STING-TRAF3-TBK1 complex. These results collectively point to a new mechanism used by SARS-CoV through which PLpro negatively regulates IRF3 activation by interaction with STING-TRAF3-TBK1 complex, yielding a SARS-CoV countermeasure against host innate immunity.",2014 May 14,"['Chen, Xiaojuan', 'Yang, Xingxing', 'Zheng, Yang', 'Yang, Yudong', 'Xing, Yaling', 'Chen, Zhongbin']",Protein Cell,,,True
68c75abe54d5b162839f0e67a9dceb28f5caeb05,PMC,Febrile Illness in the Athlete,http://dx.doi.org/10.1177/1941738113508373,PMC4000470,24790692,NO-CC CODE,"CONTEXT: Acute febrile illnesses are common in athletes over the course of training and competition seasons. Complete recovery and rapid yet safe return to participation are critical for competitive athletes. Alterations in thermoregulation, metabolism, fluid homeostasis, muscle strength, and endurance, as well as potential complications for the athlete and others, must be considered. EVIDENCE ACQUISITION: The PubMed database was searched (1970-2013) for all English-language articles related to febrile illness in sport, using the keywords fever, febrile, body temperature, thermoregulation, infection, illness, disease, exercise, athlete, sport, performance, return to play, metabolism, hydration, and dehydration. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS: Limited data confirm that febrile illness is correlated with alterations in the body’s thermoregulatory system, with increases in metabolic rate, and with effects in fluid homeostasis. Human and animal studies demonstrate a decrease in muscle strength and endurance secondary to muscle catabolism in febrile illness. However, indirect evidence suggests that regular exercise enhances the immune response. No strong clinical research has been published on return to play during or following acute febrile illness, excluding mononucleosis and myocarditis. CONCLUSION: Fever is correlated with an increase in insensible fluid losses, dehydration, metabolic demands, and dysregulation of body temperature. Fever can have detrimental effects on the musculoskeletal system, including decreasing strength and endurance, generalized muscle catabolism, and increase in perceived fatigue. Participating in strenuous exercise during febrile illness can worsen the illness and has demonstrated increased lethality in animal models. No consensus recommendations support return to activity before resolution of fever, and training should be resumed gradually once fever and dehydration have resolved.",2014 May,"['Dick, Natalie A.', 'Diehl, Jason J.']",Sports Health,,,True
39c3cd333c7f1556827c2318f07b93cb90e81553,PMC,In vitro RNA interference targeting the DNA polymerase gene inhibits orf virus replication in primary ovine fetal turbinate cells,http://dx.doi.org/10.1007/s00705-013-1896-z,PMC4010719,24178308,NO-CC CODE,"Orf, which is caused by orf virus (ORFV), is distributed worldwide and is endemic in most sheep- and/or goat-raising countries. RNA interference (RNAi) pathways have emerged as important regulators of virus-host cell interactions. In this study, the specific effect of RNAi on the replication of ORFV was explored. The application of RNA interference (RNAi) inhibited the replication of ORFV in cell culture by targeting the ORF025 gene of ORFV, which encodes the viral polymerase. Three small interfering RNA (siRNA) (named siRNA704, siRNA1017 and siRNA1388) were prepared by in vitro transcription. The siRNAs were evaluated for antiviral activity against the ORFV Jilin isolate by the observation of cytopathic effects (CPE), virus titration, and real-time PCR. After 48 h of infection, siRNA704, siRNA1017 and siRNA1388 reduced virus titers by 59- to 199-fold and reduced the level of viral replication by 73-89 %. These results suggest that these three siRNAs can efficiently inhibit ORFV genome replication and infectious virus production. RNAi targeting of the DNA polymerase gene is therefore potentially useful for studying the replication of ORFV and may have potential therapeutic applications.",2014 Nov 1,"['Wang, Gaili', 'He, Wenqi', 'Song, Deguang', 'Li, Jida', 'Bao, Yingfu', 'Lu, Rongguang', 'Bi, Jingying', 'Zhao, Kui', 'Gao, Feng']",Arch Virol,,,True
504684906ab86a5130b59c2557ec73e2226f67e7,PMC,Bat Flight and Zoonotic Viruses,http://dx.doi.org/10.3201/eid2005.130539,PMC4012789,24750692,NO-CC CODE,"Bats are sources of high viral diversity and high-profile zoonotic viruses worldwide. Although apparently not pathogenic in their reservoir hosts, some viruses from bats severely affect other mammals, including humans. Examples include severe acute respiratory syndrome coronaviruses, Ebola and Marburg viruses, and Nipah and Hendra viruses. Factors underlying high viral diversity in bats are the subject of speculation. We hypothesize that flight, a factor common to all bats but to no other mammals, provides an intensive selective force for coexistence with viral parasites through a daily cycle that elevates metabolism and body temperature analogous to the febrile response in other mammals. On an evolutionary scale, this host–virus interaction might have resulted in the large diversity of zoonotic viruses in bats, possibly through bat viruses adapting to be more tolerant of the fever response and less virulent to their natural hosts.",2014 May,"['O’Shea, Thomas J.', 'Cryan, Paul M.', 'Cunningham, Andrew A.', 'Fooks, Anthony R.', 'Hayman, David T.S.', 'Luis, Angela D.', 'Peel, Alison J.', 'Plowright, Raina K.', 'Wood, James L.N.']",Emerg Infect Dis,,,True
25781baaa25b85c1d688e32d35730300a39ac3bd,PMC,PCR for Detection of Oseltamivir Resistance Mutation in Influenza A(H7N9) Virus,http://dx.doi.org/10.3201/eid2005.131364,PMC4012804,24751348,NO-CC CODE,Sensitive molecular techniques are needed for rapid detection of the R292K oseltamivir-resistant mutant of influenza A(H7/N9) virus strain to monitor its transmission and guide antiviral treatment. We developed a real-time reverse transcription PCR and single nucleotide polymorphism probes to differentiate this mutant strain in mixed virus populations in human specimens.,2014 May,"['Wang, Wei', 'Song, Zhigang', 'Guan, Wencai', 'Liu, Yi', 'Zhang, Xiaonan', 'Xu, Lei', 'Li, Jianhua', 'Yuan, Zhenghong', 'Hu, Yunwen']",Emerg Infect Dis,,,True
978fcb9694711bd974f21203205a86d359868b3d,PMC,PCR for Detection of Oseltamivir Resistance Mutation in Influenza A(H7N9) Virus,http://dx.doi.org/10.3201/eid2005.131364,PMC4012804,24751348,NO-CC CODE,Sensitive molecular techniques are needed for rapid detection of the R292K oseltamivir-resistant mutant of influenza A(H7/N9) virus strain to monitor its transmission and guide antiviral treatment. We developed a real-time reverse transcription PCR and single nucleotide polymorphism probes to differentiate this mutant strain in mixed virus populations in human specimens.,2014 May,"['Wang, Wei', 'Song, Zhigang', 'Guan, Wencai', 'Liu, Yi', 'Zhang, Xiaonan', 'Xu, Lei', 'Li, Jianhua', 'Yuan, Zhenghong', 'Hu, Yunwen']",Emerg Infect Dis,,,True
10243aff722d36cdd14970ce1fd5d4ac737430d5,PMC,"Role of Transportation in Spread of Porcine Epidemic Diarrhea Virus Infection, United States",http://dx.doi.org/10.3201/eid2005.131628,PMC4012813,24750785,NO-CC CODE,"After porcine epidemic diarrhea virus (PEDV) was detected in the United States in 2013, we tested environmental samples from trailers in which pigs had been transported. PEDV was found in 5.2% of trailers not contaminated at arrival, , suggesting that the transport process is a source of transmission if adequate hygiene measures are not implemented.",2014 May,"['Lowe, James', 'Gauger, Phillip', 'Harmon, Karen', 'Zhang, Jianqiang', 'Connor, Joseph', 'Yeske, Paul', 'Loula, Timothy', 'Levis, Ian', 'Dufresne, Luc', 'Main, Rodger']",Emerg Infect Dis,,,True
f4d811f1ad17486fd10dad9a4a5cbbdc59b4d9ad,PMC,"Responses to Threat of Influenza A(H7N9) and Support for Live Poultry Markets, Hong Kong, 2013",http://dx.doi.org/10.3201/eid2005.131859,PMC4012820,24750988,NO-CC CODE,We conducted a population survey in Hong Kong to gauge psychological and behavioral responses to the threat of influenza A(H7N9) and support for closure of live poultry markets. We found low anxiety and low levels of exposure to live poultry but mixed support for permanent closure of the markets.,2014 May,"['Wu, Peng', 'Fang, Vicky J.', 'Liao, Qiuyan', 'Ng, Diane M.W.', 'Wu, Joseph T.', 'Leung, Gabriel M.', 'Fielding, Richard', 'Cowling, Benjamin J.']",Emerg Infect Dis,,,True
9b46571754b56f18f1485bb4d18157d23e1c7ada,PMC,"Responses to Threat of Influenza A(H7N9) and Support for Live Poultry Markets, Hong Kong, 2013",http://dx.doi.org/10.3201/eid2005.131859,PMC4012820,24750988,NO-CC CODE,We conducted a population survey in Hong Kong to gauge psychological and behavioral responses to the threat of influenza A(H7N9) and support for closure of live poultry markets. We found low anxiety and low levels of exposure to live poultry but mixed support for permanent closure of the markets.,2014 May,"['Wu, Peng', 'Fang, Vicky J.', 'Liao, Qiuyan', 'Ng, Diane M.W.', 'Wu, Joseph T.', 'Leung, Gabriel M.', 'Fielding, Richard', 'Cowling, Benjamin J.']",Emerg Infect Dis,,,False
e9d184be19d186f0c3aa85806c7f1bb4d0107160,PMC,"New Variant of Porcine Epidemic Diarrhea Virus, United States, 2014",http://dx.doi.org/10.3201/eid2005.140195,PMC4012824,24750580,NO-CC CODE,,2014 May,"['Wang, Leyi', 'Byrum, Beverly', 'Zhang, Yan']",Emerg Infect Dis,,,True
ff1cf519f153e1ebcdb5922731b28ee4e92f827c,PMC,"Signalling C-Type lectin receptors, microbial recognition and immunity",http://dx.doi.org/10.1111/cmi.12249,PMC4016756,24330199,NO-CC CODE,"Signalling C-type lectin receptors (CLRs) are crucial in shaping the immune response to fungal pathogens, but comparably little is known about the role of these receptors in bacterial, viral and parasitic infections. CLRs have many diverse functions depending on the signalling motifs in their cytoplasmic domains, and can induce endocytic, phagocytic, antimicrobial, pro-inflammatory or anti-inflammatory responses which are either protective or not during an infection. Understanding the role of CLRs in shaping anti-microbial immunity offers great potential for the future development of therapeutics for disease intervention. In this review we will focus on the recognition of bacterial, viral and parasitic pathogens by CLRs, and how these receptors influence the outcome of infection. We will also provide a brief update on the role of CLRs in antifungal immunity.",2014 Feb 10,"['Hoving, J Claire', 'Wilson, Gillian J', 'Brown, Gordon D']",Cell Microbiol,,,True
38e37fa66e4acf2931dbc37ac44d66cce82bae55,PMC,Potential for Introduction of Bat-Borne Zoonotic Viruses into the EU: A Review,http://dx.doi.org/10.3390/v6052084,PMC4036546,24841385,NO-CC CODE,"Bat-borne viruses can pose a serious threat to human health, with examples including Nipah virus (NiV) in Bangladesh and Malaysia, and Marburg virus (MARV) in Africa. To date, significant human outbreaks of such viruses have not been reported in the European Union (EU). However, EU countries have strong historical links with many of the countries where NiV and MARV are present and a corresponding high volume of commercial trade and human travel, which poses a potential risk of introduction of these viruses into the EU. In assessing the risks of introduction of these bat-borne zoonotic viruses to the EU, it is important to consider the location and range of bat species known to be susceptible to infection, together with the virus prevalence, seasonality of viral pulses, duration of infection and titre of virus in different bat tissues. In this paper, we review the current scientific knowledge of all these factors, in relation to the introduction of NiV and MARV into the EU.",2014 May 16,"['Simons, Robin R. L.', 'Gale, Paul', 'Horigan, Verity', 'Snary, Emma L.', 'Breed, Andrew C.']",Viruses,,,True
8bcf19aa1484447b3f16aa39f5f6efdaedfa5a5d,PMC,"Human Infection with MERS Coronavirus after Exposure to Infected Camels, Saudi Arabia, 2013",http://dx.doi.org/10.3201/eid2006.140402,PMC4036761,24857749,NO-CC CODE,We investigated a case of human infection with Middle East respiratory syndrome coronavirus (MERS-CoV) after exposure to infected camels. Analysis of the whole human-derived virus and 15% of the camel-derived virus sequence yielded nucleotide polymorphism signatures suggestive of cross-species transmission. Camels may act as a direct source of human MERS-CoV infection.,2014 Jun,"['Memish, Ziad A.', 'Cotten, Matthew', 'Meyer, Benjamin', 'Watson, Simon J.', 'Alsahafi, Abdullah J.', 'Al Rabeeah, Abdullah A.', 'Corman, Victor Max', 'Sieberg, Andrea', 'Makhdoom, Hatem Q.', 'Assiri, Abdullah', 'Al Masri, Malaki', 'Aldabbagh, Souhaib', 'Bosch, Berend-Jan', 'Beer, Martin', 'Müller, Marcel A.', 'Kellam, Paul', 'Drosten, Christian']",Emerg Infect Dis,,,True
5b474468e382cabf51bc7412054ce70f58f06bd6,PMC,"Human Infection with MERS Coronavirus after Exposure to Infected Camels, Saudi Arabia, 2013",http://dx.doi.org/10.3201/eid2006.140402,PMC4036761,24857749,NO-CC CODE,We investigated a case of human infection with Middle East respiratory syndrome coronavirus (MERS-CoV) after exposure to infected camels. Analysis of the whole human-derived virus and 15% of the camel-derived virus sequence yielded nucleotide polymorphism signatures suggestive of cross-species transmission. Camels may act as a direct source of human MERS-CoV infection.,2014 Jun,"['Memish, Ziad A.', 'Cotten, Matthew', 'Meyer, Benjamin', 'Watson, Simon J.', 'Alsahafi, Abdullah J.', 'Al Rabeeah, Abdullah A.', 'Corman, Victor Max', 'Sieberg, Andrea', 'Makhdoom, Hatem Q.', 'Assiri, Abdullah', 'Al Masri, Malaki', 'Aldabbagh, Souhaib', 'Bosch, Berend-Jan', 'Beer, Martin', 'Müller, Marcel A.', 'Kellam, Paul', 'Drosten, Christian']",Emerg Infect Dis,,,False
e6480c384c8c808c6d1215c72c4e540a09d944c8,PMC,Rapid Metagenomic Diagnostics for Suspected Outbreak of Severe Pneumonia,http://dx.doi.org/10.3201/eid2006.131526,PMC4036763,24857411,NO-CC CODE,,2014 Jun,"['Fischer, Nicole', 'Rohde, Holger', 'Indenbirken, Daniela', 'Günther, Thomas', 'Reumann, Kerstin', 'Lütgehetmann, Marc', 'Meyer, Thomas', 'Kluge, Stefan', 'Aepfelbacher, Martin', 'Alawi, Malik', 'Grundhoff, Adam']",Emerg Infect Dis,,,True
b846eb629d90098884d798cbfe4132db5f63562c,PMC,"MERS Coronaviruses in Dromedary Camels, Egypt",http://dx.doi.org/10.3201/eid2006.140299,PMC4036765,24856660,NO-CC CODE,"We identified the near-full-genome sequence (29,908 nt, >99%) of Middle East respiratory syndrome coronavirus (MERS-CoV) from a nasal swab specimen from a dromedary camel in Egypt. We found that viruses genetically very similar to human MERS-CoV are infecting dromedaries beyond the Arabian Peninsula, where human MERS-CoV infections have not yet been detected.",2014 Jun,"['Chu, Daniel K.W.', 'Poon, Leo L.M.', 'Gomaa, Mokhtar M.', 'Shehata, Mahmoud M.', 'Perera, Ranawaka A.P.M.', 'Abu Zeid, Dina', 'El Rifay, Amira S.', 'Siu, Lewis Y.', 'Guan, Yi', 'Webby, Richard J.', 'Ali, Mohamed A.', 'Peiris, Malik', 'Kayali, Ghazi']",Emerg Infect Dis,,,True
a5fd5dab815208bb61aa0e2f0133fe7811923158,PMC,"MERS Coronaviruses in Dromedary Camels, Egypt",http://dx.doi.org/10.3201/eid2006.140299,PMC4036765,24856660,NO-CC CODE,"We identified the near-full-genome sequence (29,908 nt, >99%) of Middle East respiratory syndrome coronavirus (MERS-CoV) from a nasal swab specimen from a dromedary camel in Egypt. We found that viruses genetically very similar to human MERS-CoV are infecting dromedaries beyond the Arabian Peninsula, where human MERS-CoV infections have not yet been detected.",2014 Jun,"['Chu, Daniel K.W.', 'Poon, Leo L.M.', 'Gomaa, Mokhtar M.', 'Shehata, Mahmoud M.', 'Perera, Ranawaka A.P.M.', 'Abu Zeid, Dina', 'El Rifay, Amira S.', 'Siu, Lewis Y.', 'Guan, Yi', 'Webby, Richard J.', 'Ali, Mohamed A.', 'Peiris, Malik', 'Kayali, Ghazi']",Emerg Infect Dis,,,False
b333e890955fbc28fc246b5e97467a0312f4def3,PMC,"Novel Phlebovirus with Zoonotic Potential Isolated from Ticks, Australia",http://dx.doi.org/10.3201/eid2006.140003,PMC4036776,24856477,NO-CC CODE,"Recently discovered tick-borne phleboviruses have been associated with severe disease and death among persons in Asia and the United States. We report the discovery of a novel tick phlebovirus in Tasmania State, Australia, that is closely related to those zoonotic viruses found in Asia and North America.",2014 Jun,"['Wang, Jianning', 'Selleck, Paul', 'Yu, Meng', 'Ha, Wendy', 'Rootes, Chrissy', 'Gales, Rosemary', 'Wise, Terry', 'Crameri, Sandra', 'Chen, Honglei', 'Broz, Ivano', 'Hyatt, Alex', 'Woods, Rupert', 'Meehan, Brian', 'McCullough, Sam', 'Wang, Lin-Fa']",Emerg Infect Dis,,,True
45f32bef75c27869b3553a11684b3212eb4319de,PMC,Unraveling the Mysteries of Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.3201/eid2006.140322,PMC4036779,24983095,NO-CC CODE,,2014 Jun,"['Watson, John T.', 'Hall, Aron J.', 'Erdman, Dean D.', 'Swerdlow, David L', 'Gerber, Susan I.']",Emerg Infect Dis,,,True
16f9fa5dc35b07c217016a843dff05fa7d9874bf,PMC,"New Hepatitis E Virus Genotype in Camels, the Middle East",http://dx.doi.org/10.3201/eid2006.140140,PMC4036782,24856611,NO-CC CODE,"In a molecular epidemiology study of hepatitis E virus (HEV) in dromedaries in Dubai, United Arab Emirates, HEV was detected in fecal samples from 3 camels. Complete genome sequencing of 2 strains showed >20% overall nucleotide difference to known HEVs. Comparative genomic and phylogenetic analyses revealed a previously unrecognized HEV genotype.",2014 Jun,"['Woo, Patrick C.Y.', 'Lau, Susanna K.P.', 'Teng, Jade L.L.', 'Tsang, Alan K. L.', 'Joseph, Marina', 'Wong, Emily Y.M.', 'Tang, Ying', 'Sivakumar, Saritha', 'Xie, Jun', 'Bai, Ru', 'Wernery, Renate', 'Wernery, Ulrich', 'Yuen, Kwok-Yung']",Emerg Infect Dis,,,True
b1bbebdace872c471e745721e079c456a42036e7,PMC,"New Hepatitis E Virus Genotype in Camels, the Middle East",http://dx.doi.org/10.3201/eid2006.140140,PMC4036782,24856611,NO-CC CODE,"In a molecular epidemiology study of hepatitis E virus (HEV) in dromedaries in Dubai, United Arab Emirates, HEV was detected in fecal samples from 3 camels. Complete genome sequencing of 2 strains showed >20% overall nucleotide difference to known HEVs. Comparative genomic and phylogenetic analyses revealed a previously unrecognized HEV genotype.",2014 Jun,"['Woo, Patrick C.Y.', 'Lau, Susanna K.P.', 'Teng, Jade L.L.', 'Tsang, Alan K. L.', 'Joseph, Marina', 'Wong, Emily Y.M.', 'Tang, Ying', 'Sivakumar, Saritha', 'Xie, Jun', 'Bai, Ru', 'Wernery, Renate', 'Wernery, Ulrich', 'Yuen, Kwok-Yung']",Emerg Infect Dis,,,False
8d7c4111c00e7c93455b3a010faf4edf568c4010,PMC,Salutogenesis: The Defining Concept for a New Healthcare System,http://dx.doi.org/10.7453/gahmj.2014.005,PMC4045099,24944875,NO-CC CODE,,2014 May 1,"['Jonas, Wayne B', 'Chez, Ronald A', 'Smith, Katherine', 'Sakallaris, Bonnie']",Glob Adv Health Med,,,True
943576d41ee9cd2a8be3379fa2ff1bc8963a3202,PMC,A comparative study of experimental mouse models of central nervous system demyelination,http://dx.doi.org/10.1038/gt.2014.33,PMC4047154,24718267,NO-CC CODE,"Several mouse models of multiple sclerosis (MS) are now available. We have established a mouse model, in which ocular infection with a recombinant HSV-1 that expresses murine IL-2 constitutively (HSV-IL-2) causes CNS demyelination in different strains of mice. This model differs from most other models in that it represents a mixture of viral and immune triggers. In the present study, we directly compared MOG(35–55), MBP(35–47), and PLP(190–209) models of EAE with our HSV-IL-2-induced MS model. Mice with HSV-IL-2-induced and MOG-induced demyelinating diseases demonstrated a similar pattern and distribution of demyelination in their brain, spinal cord, and optic nerves. In contrast, no demyelination was detected in the optic nerves of MBP- and PLP-injected mice. IFN-β injections significantly reduced demyelination in brains of all groups, in the spinal cords of the MOG and MBP groups, and completely blocked it in the spinal cords of the PLP and HSV-IL-2 groups as well as in optic nerves of MOG and HSV-IL-2 groups. In contrast to IFN-β treatment, IL-12p70 protected the HSV-IL-2 group from demyelination, while IL-4 was not effective at all in preventing demyelination. MOG-injected mice showed clinical signs of paralysis and disease-related mortality whereas mice in the other treatment groups did not. Collectively, the results indicate that the HSV-IL-2 model and the MOG model complement each other and, together, provide unique insights into the heterogeneity of human MS.",2014 Jun 10,"['Dumitrascu, Oana M.', 'Mott, Kevin R.', 'Ghiasi, Homayon']",Gene Ther,,,True
be98b0fb166e67e068fb5f7c316b6b80650ace29,PMC,A comparative study of experimental mouse models of central nervous system demyelination,http://dx.doi.org/10.1038/gt.2014.33,PMC4047154,24718267,NO-CC CODE,"Several mouse models of multiple sclerosis (MS) are now available. We have established a mouse model, in which ocular infection with a recombinant HSV-1 that expresses murine IL-2 constitutively (HSV-IL-2) causes CNS demyelination in different strains of mice. This model differs from most other models in that it represents a mixture of viral and immune triggers. In the present study, we directly compared MOG(35–55), MBP(35–47), and PLP(190–209) models of EAE with our HSV-IL-2-induced MS model. Mice with HSV-IL-2-induced and MOG-induced demyelinating diseases demonstrated a similar pattern and distribution of demyelination in their brain, spinal cord, and optic nerves. In contrast, no demyelination was detected in the optic nerves of MBP- and PLP-injected mice. IFN-β injections significantly reduced demyelination in brains of all groups, in the spinal cords of the MOG and MBP groups, and completely blocked it in the spinal cords of the PLP and HSV-IL-2 groups as well as in optic nerves of MOG and HSV-IL-2 groups. In contrast to IFN-β treatment, IL-12p70 protected the HSV-IL-2 group from demyelination, while IL-4 was not effective at all in preventing demyelination. MOG-injected mice showed clinical signs of paralysis and disease-related mortality whereas mice in the other treatment groups did not. Collectively, the results indicate that the HSV-IL-2 model and the MOG model complement each other and, together, provide unique insights into the heterogeneity of human MS.",2014 Jun 10,"['Dumitrascu, Oana M.', 'Mott, Kevin R.', 'Ghiasi, Homayon']",Gene Ther,,,False
7317e3c5fd2c9bd0c1581a9e05b11d5e4203c622,PMC,Management of sepsis in neutropenic patients: 2014 updated guidelines from the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO),http://dx.doi.org/10.1007/s00277-014-2086-0,PMC4050292,24777705,NO-CC CODE,"Sepsis is a major cause of mortality during the neutropenic phase after intensive cytotoxic therapies for malignancies. Improved management of sepsis during neutropenia may reduce the mortality of cancer therapies. Clinical guidelines on sepsis treatment have been published by others. However, optimal management may differ between neutropenic and non-neutropenic patients. Our aim is to give evidence-based recommendations for haematologist, oncologists and intensive care physicians on how to manage adult patients with neutropenia and sepsis.",2014 Apr 29,"['Penack, Olaf', 'Becker, Carolin', 'Buchheidt, Dieter', 'Christopeit, Maximilian', 'Kiehl, Michael', 'von Lilienfeld-Toal, Marie', 'Hentrich, Marcus', 'Reinwald, Marc', 'Salwender, Hans', 'Schalk, Enrico', 'Schmidt-Hieber, Martin', 'Weber, Thomas', 'Ostermann, Helmut']",Ann Hematol,,,True
af13aa4011a57e2670ce8204394e3a11f173109d,PMC,Poly(amidoamine) Dendrimer Nanocarriers and Their Aerosol Formulations for siRNA Delivery to the Lung Epithelium,http://dx.doi.org/10.1021/mp4006358,PMC4051247,24811243,NO-CC CODE,"[Image: see text] Small interfering RNA (siRNA)-based therapies have great promise in the treatment of a number of prevalent pulmonary disorders including lung cancer, asthma and cystic fibrosis. However, progress in this area has been hindered due to the lack of carriers that can efficiently deliver siRNA to lung epithelial cells, and also due to challenges in developing oral inhalation (OI) formulations for the regional administration of siRNA and their carriers to the lungs. In this work we report the ability of generation four, amine-terminated poly(amidoamine) (PAMAM) dendrimer (G4NH2)–siRNA complexes (dendriplexes) to silence the enhanced green fluorescent protein (eGFP) gene on A549 lung alveolar epithelial cells stably expressing eGFP. We also report the formulation of the dendriplexes and their aerosol characteristics in propellant-based portable OI devices. The size and gene silencing ability of the dendriplexes was seen not to be a strong function of the N/P ratio. Silencing efficiencies of up to 40% are reported. Stable dispersions of the dendriplexes encapsulated in mannitol and also in a biodegradable and water-soluble co-oligomer were prepared in hydrofluoroalkane (HFA)-based pressurized metered-dose inhalers (pMDIs). Their aerosol characteristics were very favorable, and conducive to deep lung deposition, with respirable fractions of up to 77%. Importantly, siRNA formulated as dendriplexes in pMDIs was shown to keep its integrity after the particle preparation processes, and also after long-term exposures to HFA. The relevance of this study stems from the fact that this is the first work to report the formulation of inhalable siRNA with aerosol properties suitable to deep lung deposition using pMDIs devices that are the least expensive and most widely used portable inhalers. This study is relevant because, also for the first time, it shows that siRNA–G4NH2 dendriplexes can efficiently target lung alveolar epithelial A549 cells and silence genes even after siRNA has been exposed to the propellant environment.",2014 Jun 2,"['Conti, Denise S.', 'Brewer, Daniel', 'Grashik, Jordan', 'Avasarala, Sumant', 'da Rocha, Sandro R. P.']",Mol Pharm,,,True
174406471afbd68d911a4e2f3033a40b7baa7765,PMC,Poly(amidoamine) Dendrimer Nanocarriers and Their Aerosol Formulations for siRNA Delivery to the Lung Epithelium,http://dx.doi.org/10.1021/mp4006358,PMC4051247,24811243,NO-CC CODE,"[Image: see text] Small interfering RNA (siRNA)-based therapies have great promise in the treatment of a number of prevalent pulmonary disorders including lung cancer, asthma and cystic fibrosis. However, progress in this area has been hindered due to the lack of carriers that can efficiently deliver siRNA to lung epithelial cells, and also due to challenges in developing oral inhalation (OI) formulations for the regional administration of siRNA and their carriers to the lungs. In this work we report the ability of generation four, amine-terminated poly(amidoamine) (PAMAM) dendrimer (G4NH2)–siRNA complexes (dendriplexes) to silence the enhanced green fluorescent protein (eGFP) gene on A549 lung alveolar epithelial cells stably expressing eGFP. We also report the formulation of the dendriplexes and their aerosol characteristics in propellant-based portable OI devices. The size and gene silencing ability of the dendriplexes was seen not to be a strong function of the N/P ratio. Silencing efficiencies of up to 40% are reported. Stable dispersions of the dendriplexes encapsulated in mannitol and also in a biodegradable and water-soluble co-oligomer were prepared in hydrofluoroalkane (HFA)-based pressurized metered-dose inhalers (pMDIs). Their aerosol characteristics were very favorable, and conducive to deep lung deposition, with respirable fractions of up to 77%. Importantly, siRNA formulated as dendriplexes in pMDIs was shown to keep its integrity after the particle preparation processes, and also after long-term exposures to HFA. The relevance of this study stems from the fact that this is the first work to report the formulation of inhalable siRNA with aerosol properties suitable to deep lung deposition using pMDIs devices that are the least expensive and most widely used portable inhalers. This study is relevant because, also for the first time, it shows that siRNA–G4NH2 dendriplexes can efficiently target lung alveolar epithelial A549 cells and silence genes even after siRNA has been exposed to the propellant environment.",2014 Jun 2,"['Conti, Denise S.', 'Brewer, Daniel', 'Grashik, Jordan', 'Avasarala, Sumant', 'da Rocha, Sandro R. P.']",Mol Pharm,,,True
4ca9a831e8193830fab1a4c09a70b2048c174d0c,PMC,"Frequency of human bocavirus (HBoV) infection among children with febrile respiratory symptoms in Argentina, Nicaragua and Peru",http://dx.doi.org/10.1111/j.1750-2659.2010.00160.x,PMC4066840,21138534,NO-CC CODE,"Please cite this paper as: Salmón‐Mulanovich et al. (2010) Frequency of human bocavirus (HBoV) infection among children with febrile respiratory symptoms in Argentina, Nicaragua and Peru. Influenza and Other Respiratory Viruses 5(1), 1–5. Background  Globally, respiratory infections are the primary cause of illness in developing countries, specifically among children; however, an etiological agent for many of these illnesses is rarely identified. Objectives  Our study aimed to estimate the frequency of human bocavirus (HBoV) infection among pediatric populations in Argentina, Nicaragua and Peru. Methods  We conducted a cross‐sectional study using stored samples of an influenza‐like illness surveillance program. Irrespective of previous diagnosis, nasopharyngeal or nasal swab specimens were randomly selected and tested using real‐time PCR from three sites during 2007 from patients younger than 6 years old. Results  A total of 568 specimens from Argentina (185), Nicaragua (192) and Peru (191) were tested. The prevalence of HBoV was 10·8% (95% CI: 6·3; 15·3) in Argentina, 33·3% in Nicaragua (95% CI: 26·6; 40·1) and 25·1% in Peru (95% CI: 18·9; 31·3). Conclusions  These findings demonstrate circulation of HBoV in Argentina, Nicaragua and Peru among children with influenza‐like symptoms enrolled in a sentinel surveillance program.",2011 Jan 16,"['Salmón‐Mulanovich, Gabriela', 'Sovero, Merly', 'Laguna‐Torres, V. Alberto', 'Kochel, Tadeusz J.', 'Lescano, Andres G.', 'Chauca, Gloria', 'Sanchez, J. Felix', 'Rodriguez, Francisco', 'Parrales, Eduardo', 'Ocaña, Victor', 'Barrantes, Melvin', 'Blazes, David L.', 'Montgomery, Joel M.']",Influenza Other Respir Viruses,,,True
6aadca94314fe7e81e278fbbef178f2a5bf4f538,PMC,Lower airway sampling greatly increases detection of respiratory viruses in critically ill patients: the COURSE study,http://dx.doi.org/10.1186/cc13531,PMC4069511,,NO-CC CODE,,2014 Mar 17,"['Van Someren Gréve, F', 'Van der Sluijs, KF', 'Juffermans, NP', 'Winters, T', 'Rebers, SP', 'SPVerheul, KD', 'Molenkamp, R', 'Spoelstra-de Man, AM', 'Spronk, P', 'De Jong, MD', 'Schultz, MJ']",Crit Care,,,True
ea36a40b76e233b4f7d69d38d9ce3741ccd710b4,PMC,"Outbreak-Related Porcine Epidemic Diarrhea Virus Strains Similar to US Strains, South Korea, 2013",http://dx.doi.org/10.3201/eid2007.140294,PMC4073847,24960370,NO-CC CODE,"In late 2013, outbreaks of porcine epidemic diarrhea virus (PEDV) infection recurred in South Korea. Genetic and phylogenetic analyses showed that isolates from the outbreaks were most closely related to emergent US strains of PEDV. These US strain–like PEDV variants are prevalent in South Korea and responsible for recent outbreaks in the country.",2014 Jul,"['Lee, Sunhee', 'Lee, Changhee']",Emerg Infect Dis,,,True
09842c75bf02714b8e4ae301e7eb88bd82b11890,PMC,"Outbreak-Related Porcine Epidemic Diarrhea Virus Strains Similar to US Strains, South Korea, 2013",http://dx.doi.org/10.3201/eid2007.140294,PMC4073847,24960370,NO-CC CODE,"In late 2013, outbreaks of porcine epidemic diarrhea virus (PEDV) infection recurred in South Korea. Genetic and phylogenetic analyses showed that isolates from the outbreaks were most closely related to emergent US strains of PEDV. These US strain–like PEDV variants are prevalent in South Korea and responsible for recent outbreaks in the country.",2014 Jul,"['Lee, Sunhee', 'Lee, Changhee']",Emerg Infect Dis,,,False
868afcaa176cdfdc50900313a5657583d5a74e9e,PMC,"Detection and Genetic Characterization of Deltacoronavirus in Pigs, Ohio, USA, 2014",http://dx.doi.org/10.3201/eid2007.140296,PMC4073853,24964136,NO-CC CODE,"In Ohio, United States, in early 2014, a deltacoronavirus was detected in feces and intestine samples from pigs with diarrheal disease. The complete genome sequence and phylogenetic analysis of the virus confirmed that the virus is closely related to a porcine deltacoronavirus (porcine coronavirus HKU15) reported in Hong Kong in 2012.",2014 Jul,"['Wang, Leyi', 'Byrum, Beverly', 'Zhang, Yan']",Emerg Infect Dis,,,True
346f7bb753e53598554deae2f428d0ce66a8320a,PMC,"MERS Coronavirus in Dromedary Camel Herd, Saudi Arabia",http://dx.doi.org/10.3201/eid2007.140571,PMC4073860,24964193,NO-CC CODE,A prospective study of a dromedary camel herd during the 2013–14 calving season showed Middle East respiratory syndrome coronavirus infection of calves and adults. Virus was isolated from the nose and feces but more frequently from the nose. Preexisting neutralizing antibody did not appear to protect against infection.,2014 Jul,"['Hemida, Maged G.', 'Chu, Daniel K.W.', 'Poon, Leo L.M.', 'Perera, Ranawaka A.P.M.', 'Alhammadi, Mohammad A.', 'Ng, Hoi-yee', 'Siu, Lewis Y.', 'Guan, Yi', 'Alnaeem, Abdelmohsen', 'Peiris, Malik']",Emerg Infect Dis,,,True
fe6434ef100a24a5528ba225163380cf0131dfbe,PMC,"MERS Coronavirus in Dromedary Camel Herd, Saudi Arabia",http://dx.doi.org/10.3201/eid2007.140571,PMC4073860,24964193,NO-CC CODE,A prospective study of a dromedary camel herd during the 2013–14 calving season showed Middle East respiratory syndrome coronavirus infection of calves and adults. Virus was isolated from the nose and feces but more frequently from the nose. Preexisting neutralizing antibody did not appear to protect against infection.,2014 Jul,"['Hemida, Maged G.', 'Chu, Daniel K.W.', 'Poon, Leo L.M.', 'Perera, Ranawaka A.P.M.', 'Alhammadi, Mohammad A.', 'Ng, Hoi-yee', 'Siu, Lewis Y.', 'Guan, Yi', 'Alnaeem, Abdelmohsen', 'Peiris, Malik']",Emerg Infect Dis,,,True
f433bb9c63b678e5ff5c981a1bfe5aad92392218,PMC,Stability of Middle East Respiratory Syndrome Coronavirus in Milk,http://dx.doi.org/10.3201/eid2007.140500,PMC4073862,24960335,NO-CC CODE,,2014 Jul,"['van Doremalen, Neeltje', 'Bushmaker, Trenton', 'Karesh, William B.', 'Munster, Vincent J.']",Emerg Infect Dis,,,True
cbb912f90a472343d8910eb0e4c02b5d8811269c,PMC,"MERS–Related Betacoronavirus in Vespertilio superans Bats, China",http://dx.doi.org/10.3201/eid2007.140318,PMC4073873,24960574,NO-CC CODE,,2014 Jul,"['Yang, Li', 'Wu, Zhiqiang', 'Ren, Xianwen', 'Yang, Fan', 'Zhang, Junpeng', 'He, Guimei', 'Dong, Jie', 'Sun, Lilian', 'Zhu, Yafang', 'Zhang, Shuyi', 'Jin, Qi']",Emerg Infect Dis,,,True
f12e63706cefe31a00a3921ce2ff6dcbed75b5c0,PMC,"MERS–Related Betacoronavirus in Vespertilio superans Bats, China",http://dx.doi.org/10.3201/eid2007.140318,PMC4073873,24960574,NO-CC CODE,,2014 Jul,"['Yang, Li', 'Wu, Zhiqiang', 'Ren, Xianwen', 'Yang, Fan', 'Zhang, Junpeng', 'He, Guimei', 'Dong, Jie', 'Sun, Lilian', 'Zhu, Yafang', 'Zhang, Shuyi', 'Jin, Qi']",Emerg Infect Dis,,,False
f906cbd97a70362b2645796aea712e3b5ce8dd7b,PMC,Innate immune responses and neuroepithelial degeneration and regeneration in the mouse olfactory mucosa induced by intranasal administration of Poly(I:C),http://dx.doi.org/10.1007/s00441-014-1848-2,PMC4077259,24744264,NO-CC CODE,"The pathogenesis of postviral olfactory disorder (PVOD) has not been fully elucidated. We investigated morphological changes and innate immune responses in the mouse olfactory mucosa induced by intranasal administration of polyinosinic-polycytidylic acid [Poly(I:C)], a synthetic analog of viral double-stranded RNA. Mice received three administrations of saline with or without Poly(I:C), once every 24 h. The olfactory mucosa was harvested at various intervals after the first administration (8 h, 3, 9 and 24 days). In the Poly(I:C) group, the number of apoptotic cells in the olfactory neuroepithelium had increased at 8 h. At 9 days, the olfactory neuroepithelium had severely degenerated and behavioral tests demonstrated that the mice showed signs of olfactory deterioration. At 24 days, the structure of the neuroepithelium had regenerated almost completely. Regarding the innate immune responses, many neutrophils had infiltrated the olfactory neuroepithelium at 8 h and had exuded into the nasal cavity by 3 days. Macrophages had also infiltrated the olfactory neuroepithelium at 8 h although to a lesser extent, but they still remained in the neuroepithelium at 24 days. Poly(I:C)-induced neuroepithelial damage was significantly inhibited by a neutrophil elastase inhibitor and was suppressed in neutropenic model mice. These findings suggest that the secondary damage caused by the neutrophil-mediated innate immune response plays an important role in the pathogenesis of PVOD.",2014 Apr 18,"['Kanaya, Kaori', 'Kondo, Kenji', 'Suzukawa, Keigo', 'Sakamoto, Takashi', 'Kikuta, Shu', 'Okada, Kazunari', 'Yamasoba, Tatsuya']",Cell Tissue Res,,,True
0cf35bb67d4a9d57d3482d3acc790525eab934eb,PMC,Structure and Dynamics of the HIV-1 Frameshift Element RNA,http://dx.doi.org/10.1021/bi5004926,PMC4089884,24926888,NO-CC CODE,"[Image: see text] The HIV-1 ribosomal frameshift element is highly structured, regulates translation of all virally encoded enzymes, and is a promising therapeutic target. The prior model for this motif contains two helices separated by a three-nucleotide bulge. Modifications to this model were suggested by SHAPE chemical probing of an entire HIV-1 RNA genome. Novel features of the SHAPE-directed model include alternate helical conformations and a larger, more complex structure. These structural elements also support the presence of a secondary frameshift site within the frameshift domain. Here, we use oligonucleotide-directed structure perturbation, probing in the presence of formamide, and in-virion experiments to examine these models. Our data support a model in which the frameshift domain is anchored by a stable helix outside the conventional domain. Less stable helices within the domain can switch from the SHAPE-predicted to the two-helix conformation. Translational frameshifting assays with frameshift domain mutants support a functional role for the interactions predicted by and specific to the SHAPE-directed model. These results reveal that the HIV-1 frameshift domain is a complex, dynamic structure and underscore the importance of analyzing folding in the context of full-length RNAs.",2014 Jul 8,"['Low, Justin\nT.', 'Garcia-Miranda, Pablo', 'Mouzakis, Kathryn D.', 'Gorelick, Robert J.', 'Butcher, Samuel E.', 'Weeks, Kevin M.']",Biochemistry,,,True
8666c0d92dc4d0de2839600559228d4dd07f487f,PMC,Structure and Dynamics of the HIV-1 Frameshift Element RNA,http://dx.doi.org/10.1021/bi5004926,PMC4089884,24926888,NO-CC CODE,"[Image: see text] The HIV-1 ribosomal frameshift element is highly structured, regulates translation of all virally encoded enzymes, and is a promising therapeutic target. The prior model for this motif contains two helices separated by a three-nucleotide bulge. Modifications to this model were suggested by SHAPE chemical probing of an entire HIV-1 RNA genome. Novel features of the SHAPE-directed model include alternate helical conformations and a larger, more complex structure. These structural elements also support the presence of a secondary frameshift site within the frameshift domain. Here, we use oligonucleotide-directed structure perturbation, probing in the presence of formamide, and in-virion experiments to examine these models. Our data support a model in which the frameshift domain is anchored by a stable helix outside the conventional domain. Less stable helices within the domain can switch from the SHAPE-predicted to the two-helix conformation. Translational frameshifting assays with frameshift domain mutants support a functional role for the interactions predicted by and specific to the SHAPE-directed model. These results reveal that the HIV-1 frameshift domain is a complex, dynamic structure and underscore the importance of analyzing folding in the context of full-length RNAs.",2014 Jul 8,"['Low, Justin\nT.', 'Garcia-Miranda, Pablo', 'Mouzakis, Kathryn D.', 'Gorelick, Robert J.', 'Butcher, Samuel E.', 'Weeks, Kevin M.']",Biochemistry,,,False
aacbe6a4b7636a58ee07716296eae9ec499bbc3f,PMC,Interferon-α2b and ribavirin treatment improves outcome in MERS-CoV-infected rhesus macaques,http://dx.doi.org/10.1038/nm.3362,PMC4093902,24013700,NO-CC CODE,"The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of global concern – causing severe respiratory illness with 97 confirmed cases and 46 deaths(1). Therapeutic interventions have not been evaluated in vivo, thus patient management relies exclusively on supportive care, which given the high case-fatality rate is not highly effective. The rhesus macaque is the only known disease model for MERS-CoV, developing an acute localized-to-widespread pneumonia with transient clinical disease(2,3) that recapitulates mild-to-moderate human MERS-CoV cases(4,5). The combination of interferon-α2b and ribavirin was effective in reducing MERS-CoV replication in vitro(6); therefore, this strategy was initiated 8 h post-infection in the rhesus macaque model. Treated animals did not develop breathing abnormalities and showed no-to-very mild radiographic evidence of pneumonia. Moreover, treated animals showed reduced levels of systemic (serum) and local (lung) proinflammatory markers in addition to reduced viral genome copies, altered gene expression and less severe histopathological changes in the lungs. Taken together, these data suggest that treatment of MERS-CoV infected rhesus macaques with IFN-α2b and ribavirin reduces virus replication, moderates the host response and improves clinical outcome. As these two drugs are already used in combination in the clinic, IFN-α2b and ribavirin should be considered for management of MERS-CoV cases.",2013 Oct 8,"['Falzarano, Darryl', 'de Wit, Emmie', 'Rasmussen, Angela L.', 'Feldmann, Friederike', 'Okumura, Atsushi', 'Scott, Dana P.', 'Brining, Doug', 'Bushmaker, Trenton', 'Martellaro, Cynthia', 'Baseler, Laura', 'Benecke, Arndt G.', 'Katze, Michael G.', 'Munster, Vincent J.', 'Feldmann, Heinz']",Nat Med,,,True
397b105a757d1d6241a7b1b77b49a768513c81e7,PMC,Interferon-α2b and ribavirin treatment improves outcome in MERS-CoV-infected rhesus macaques,http://dx.doi.org/10.1038/nm.3362,PMC4093902,24013700,NO-CC CODE,"The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of global concern – causing severe respiratory illness with 97 confirmed cases and 46 deaths(1). Therapeutic interventions have not been evaluated in vivo, thus patient management relies exclusively on supportive care, which given the high case-fatality rate is not highly effective. The rhesus macaque is the only known disease model for MERS-CoV, developing an acute localized-to-widespread pneumonia with transient clinical disease(2,3) that recapitulates mild-to-moderate human MERS-CoV cases(4,5). The combination of interferon-α2b and ribavirin was effective in reducing MERS-CoV replication in vitro(6); therefore, this strategy was initiated 8 h post-infection in the rhesus macaque model. Treated animals did not develop breathing abnormalities and showed no-to-very mild radiographic evidence of pneumonia. Moreover, treated animals showed reduced levels of systemic (serum) and local (lung) proinflammatory markers in addition to reduced viral genome copies, altered gene expression and less severe histopathological changes in the lungs. Taken together, these data suggest that treatment of MERS-CoV infected rhesus macaques with IFN-α2b and ribavirin reduces virus replication, moderates the host response and improves clinical outcome. As these two drugs are already used in combination in the clinic, IFN-α2b and ribavirin should be considered for management of MERS-CoV cases.",2013 Oct 8,"['Falzarano, Darryl', 'de Wit, Emmie', 'Rasmussen, Angela L.', 'Feldmann, Friederike', 'Okumura, Atsushi', 'Scott, Dana P.', 'Brining, Doug', 'Bushmaker, Trenton', 'Martellaro, Cynthia', 'Baseler, Laura', 'Benecke, Arndt G.', 'Katze, Michael G.', 'Munster, Vincent J.', 'Feldmann, Heinz']",Nat Med,,,False
d03888523e81c821f95247b544bdfac0c94a8b0c,PMC,Design and implementation of needs-specific critical care response teams,http://dx.doi.org/10.1186/cc5604,PMC4095497,,NO-CC CODE,,2007 Mar 22,"['Hodder, R', 'Fox-Robichaud, A', 'Wax, R', 'Cardinal, P', 'Reynolds, S']",Crit Care,,,True
57a67fd5273fb4aac8505d1ae7b32c2582d12df3,PMC,Physicochemical Properties of Cells and Their Effects on Intrinsically Disordered Proteins (IDPs),http://dx.doi.org/10.1021/cr400695p,PMC4095937,24901537,NO-CC CODE,,2014 Jul 9,"['Theillet, Francois-Xavier', 'Binolfi, Andres', 'Frembgen-Kesner, Tamara', 'Hingorani, Karan', 'Sarkar, Mohona', 'Kyne, Ciara', 'Li, Conggang', 'Crowley, Peter B.', 'Gierasch, Lila', 'Pielak, Gary J.', 'Elcock, Adrian H.', 'Gershenson, Anne', 'Selenko, Philipp']",Chem Rev,,,True
72a5640aa0c307fbe171ca7ad55d3fda48b53988,PMC,Computerised tomography (CT) in severe acute respiratory syndrome (SARS): late-stage acute respiratory disease syndrome (ARDS) and follow-up findings,http://dx.doi.org/10.1186/cc2504,PMC4099624,,NO-CC CODE,,2004 Mar 15,"['Joynt, G', 'Antonio, G', 'Wong, K', 'Lam, P', 'Gomersall, C', 'Li, T']",Crit Care,,,True
72a5640aa0c307fbe171ca7ad55d3fda48b53988,PMC,Critically ill patients with severe acute respiratory syndrome (SARS) in a designated national SARS ICU: clinical features and predictors for mortality,http://dx.doi.org/10.1186/cc2505,PMC4099625,,NO-CC CODE,,2004 Mar 15,"['Tai, D', 'Lew, T', 'Loo, S', 'Earnest, A', 'Chen, M']",Crit Care,,,True
72a5640aa0c307fbe171ca7ad55d3fda48b53988,PMC,Retrospective analysis of critically ill patients with severe acute respiratory syndrome admitted to an intensive care unit,http://dx.doi.org/10.1186/cc2506,PMC4099626,,NO-CC CODE,,2004 Mar 15,"Buckley, T",Crit Care,,,True
72a5640aa0c307fbe171ca7ad55d3fda48b53988,PMC,Increase in methicillin-resistant Staphylococcus aureus acquisition and change in pathogen pattern associated with outbreaks of severe acute respiratory syndrome (SARS),http://dx.doi.org/10.1186/cc2687,PMC4099807,,NO-CC CODE,,2004 Mar 15,"Yap, F",Crit Care,,,True
dd5f28bd9fee1733222b8816932316ad81964826,PMC,Oxidative tissue injury in multiple sclerosis is only partly reflected in experimental disease models,http://dx.doi.org/10.1007/s00401-014-1263-5,PMC4102830,24622774,NO-CC CODE,"Recent data suggest that oxidative injury may play an important role in demyelination and neurodegeneration in multiple sclerosis (MS). We compared the extent of oxidative injury in MS lesions with that in experimental models driven by different inflammatory mechanisms. It was only in a model of coronavirus-induced demyelinating encephalomyelitis that we detected an accumulation of oxidised phospholipids, which was comparable in extent to that in MS. In both, MS and coronavirus-induced encephalomyelitis, this was associated with massive microglial and macrophage activation, accompanied by the expression of the NADPH oxidase subunit p22phox but only sparse expression of inducible nitric oxide synthase (iNOS). Acute and chronic CD4(+) T cell-mediated experimental autoimmune encephalomyelitis lesions showed transient expression of p22phox and iNOS associated with inflammation. Macrophages in chronic lesions of antibody-mediated demyelinating encephalomyelitis showed lysosomal activity but very little p22phox or iNOS expressions. Active inflammatory demyelinating lesions induced by CD8(+) T cells or by innate immunity showed macrophage and microglial activation together with the expression of p22phox, but low or absent iNOS reactivity. We corroborated the differences between acute CD4(+) T cell-mediated experimental autoimmune encephalomyelitis and acute MS lesions via gene expression studies. Furthermore, age-dependent iron accumulation and lesion-associated iron liberation, as occurring in the human brain, were only minor in rodent brains. Our study shows that oxidative injury and its triggering mechanisms diverge in different models of rodent central nervous system inflammation. The amplification of oxidative injury, which has been suggested in MS, is only reflected to a limited degree in the studied rodent models. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-014-1263-5) contains supplementary material, which is available to authorized users.",2014 Mar 13,"['Schuh, Cornelia', 'Wimmer, Isabella', 'Hametner, Simon', 'Haider, Lukas', 'Van Dam, Anne-Marie', 'Liblau, Roland S.', 'Smith, Ken J.', 'Probert, Lesley', 'Binder, Christoph J.', 'Bauer, Jan', 'Bradl, Monika', 'Mahad, Don', 'Lassmann, Hans']",Acta Neuropathol,,,True
bf5c9b9133105871316b57136a6d2926303d3ebe,PMC,Oxidative tissue injury in multiple sclerosis is only partly reflected in experimental disease models,http://dx.doi.org/10.1007/s00401-014-1263-5,PMC4102830,24622774,NO-CC CODE,"Recent data suggest that oxidative injury may play an important role in demyelination and neurodegeneration in multiple sclerosis (MS). We compared the extent of oxidative injury in MS lesions with that in experimental models driven by different inflammatory mechanisms. It was only in a model of coronavirus-induced demyelinating encephalomyelitis that we detected an accumulation of oxidised phospholipids, which was comparable in extent to that in MS. In both, MS and coronavirus-induced encephalomyelitis, this was associated with massive microglial and macrophage activation, accompanied by the expression of the NADPH oxidase subunit p22phox but only sparse expression of inducible nitric oxide synthase (iNOS). Acute and chronic CD4(+) T cell-mediated experimental autoimmune encephalomyelitis lesions showed transient expression of p22phox and iNOS associated with inflammation. Macrophages in chronic lesions of antibody-mediated demyelinating encephalomyelitis showed lysosomal activity but very little p22phox or iNOS expressions. Active inflammatory demyelinating lesions induced by CD8(+) T cells or by innate immunity showed macrophage and microglial activation together with the expression of p22phox, but low or absent iNOS reactivity. We corroborated the differences between acute CD4(+) T cell-mediated experimental autoimmune encephalomyelitis and acute MS lesions via gene expression studies. Furthermore, age-dependent iron accumulation and lesion-associated iron liberation, as occurring in the human brain, were only minor in rodent brains. Our study shows that oxidative injury and its triggering mechanisms diverge in different models of rodent central nervous system inflammation. The amplification of oxidative injury, which has been suggested in MS, is only reflected to a limited degree in the studied rodent models. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-014-1263-5) contains supplementary material, which is available to authorized users.",2014 Mar 13,"['Schuh, Cornelia', 'Wimmer, Isabella', 'Hametner, Simon', 'Haider, Lukas', 'Van Dam, Anne-Marie', 'Liblau, Roland S.', 'Smith, Ken J.', 'Probert, Lesley', 'Binder, Christoph J.', 'Bauer, Jan', 'Bradl, Monika', 'Mahad, Don', 'Lassmann, Hans']",Acta Neuropathol,,,True
14b39f322085ccc2513a1180bb7c5fa9ca9002e0,PMC,"Antibodies against MERS Coronavirus in Dromedary Camels, Kenya, 1992–2013",http://dx.doi.org/10.3201/eid2008.140596,PMC4111164,25075637,NO-CC CODE,Dromedary camels are a putative source for human infections with Middle East respiratory syndrome coronavirus. We showed that camels sampled in different regions in Kenya during 1992–2013 have antibodies against this virus. High densities of camel populations correlated with increased seropositivity and might be a factor in predicting long-term virus maintenance.,2014 Aug,"['Corman, Victor M.', 'Jores, Joerg', 'Meyer, Benjamin', 'Younan, Mario', 'Liljander, Anne', 'Said, Mohammed Y.', 'Gluecks, Ilona', 'Lattwein, Erik', 'Bosch, Berend-Jan', 'Drexler, Jan Felix', 'Bornstein, Set', 'Drosten, Christian', 'Müller, Marcel A.']",Emerg Infect Dis,,,True
1acc5991023fac8c30fe7a675138ff3aae0628dd,PMC,"Antibodies against MERS Coronavirus in Dromedary Camels, Kenya, 1992–2013",http://dx.doi.org/10.3201/eid2008.140596,PMC4111164,25075637,NO-CC CODE,Dromedary camels are a putative source for human infections with Middle East respiratory syndrome coronavirus. We showed that camels sampled in different regions in Kenya during 1992–2013 have antibodies against this virus. High densities of camel populations correlated with increased seropositivity and might be a factor in predicting long-term virus maintenance.,2014 Aug,"['Corman, Victor M.', 'Jores, Joerg', 'Meyer, Benjamin', 'Younan, Mario', 'Liljander, Anne', 'Said, Mohammed Y.', 'Gluecks, Ilona', 'Lattwein, Erik', 'Bosch, Berend-Jan', 'Drexler, Jan Felix', 'Bornstein, Set', 'Drosten, Christian', 'Müller, Marcel A.']",Emerg Infect Dis,,,False
36817ab59a9f5a607f7cdc110e6d7930f5a45658,PMC,"Geographic Distribution of MERS Coronavirus among Dromedary Camels, Africa",http://dx.doi.org/10.3201/eid2008.140590,PMC4111168,25062254,NO-CC CODE,"We found serologic evidence for the circulation of Middle East respiratory syndrome coronavirus among dromedary camels in Nigeria, Tunisia, and Ethiopia. Circulation of the virus among dromedaries across broad areas of Africa may indicate that this disease is currently underdiagnosed in humans outside the Arabian Peninsula.",2014 Aug,"['Reusken, Chantal B.E.M.', 'Messadi, Lilia', 'Feyisa, Ashenafi', 'Ularamu, Hussaini', 'Godeke, Gert-Jan', 'Danmarwa, Agom', 'Dawo, Fufa', 'Jemli, Mohamed', 'Melaku, Simenew', 'Shamaki, David', 'Woma, Yusuf', 'Wungak, Yiltawe', 'Gebremedhin, Endrias Zewdu', 'Zutt, Ilse', 'Bosch, Berend-Jan', 'Haagmans, Bart L.', 'Koopmans, Marion P.G.']",Emerg Infect Dis,,,True
641c948cea542b5db2ff6d251a7698e476f6396d,PMC,"Human Exposure to Live Poultry and Psychological and Behavioral Responses to Influenza A(H7N9), China",http://dx.doi.org/10.3201/eid2008.131821,PMC4111172,25076186,NO-CC CODE,"To investigate human exposure to live poultry and changes in risk perception and behavior after the April 2013 influenza A(H7N9) outbreak in China, we surveyed 2,504 urban residents in 5 cities and 1,227 rural residents in 4 provinces and found that perceived risk for influenza A(H7N9) was low. The highest rate of exposure to live poultry was reported in Guangzhou, where 47% of those surveyed reported visiting a live poultry market >1 times in the previous year. Most (77%) urban respondents reported that they visited live markets less often after influenza A(H7N9) cases were first identified in China in March 2013, but only 30% supported permanent closure of the markets to control the epidemic. In rural areas, 48% of respondents reported that they raised backyard poultry. Exposure to live commercial and private poultry is common in urban and rural China and remains a potential risk factor for human infection with novel influenza viruses.",2014 Aug,"['Wang, Liping', 'Cowling, Benjamin J.', 'Wu, Peng', 'Yu, Jianxing', 'Li, Fu', 'Zeng, Lingjia', 'Wu, Joseph T.', 'Li, Zhongjie', 'Leung, Gabriel M.', 'Yu, Hongjie']",Emerg Infect Dis,,,True
f43d3c2c24521416b51016a809f64543c5c7fc78,PMC,"Human Exposure to Live Poultry and Psychological and Behavioral Responses to Influenza A(H7N9), China",http://dx.doi.org/10.3201/eid2008.131821,PMC4111172,25076186,NO-CC CODE,"To investigate human exposure to live poultry and changes in risk perception and behavior after the April 2013 influenza A(H7N9) outbreak in China, we surveyed 2,504 urban residents in 5 cities and 1,227 rural residents in 4 provinces and found that perceived risk for influenza A(H7N9) was low. The highest rate of exposure to live poultry was reported in Guangzhou, where 47% of those surveyed reported visiting a live poultry market >1 times in the previous year. Most (77%) urban respondents reported that they visited live markets less often after influenza A(H7N9) cases were first identified in China in March 2013, but only 30% supported permanent closure of the markets to control the epidemic. In rural areas, 48% of respondents reported that they raised backyard poultry. Exposure to live commercial and private poultry is common in urban and rural China and remains a potential risk factor for human infection with novel influenza viruses.",2014 Aug,"['Wang, Liping', 'Cowling, Benjamin J.', 'Wu, Peng', 'Yu, Jianxing', 'Li, Fu', 'Zeng, Lingjia', 'Wu, Joseph T.', 'Li, Zhongjie', 'Leung, Gabriel M.', 'Yu, Hongjie']",Emerg Infect Dis,,,False
bbb82b5cc6363d7e376af1d92e30ea59c0807f7b,PMC,"Isolation of MERS Coronavirus from a Dromedary Camel, Qatar, 2014",http://dx.doi.org/10.3201/eid2008.140663,PMC4111206,25075761,NO-CC CODE,"We obtained the full genome of Middle East respiratory syndrome coronavirus (MERS-CoV) from a camel in Qatar. This virus is highly similar to the human England/Qatar 1 virus isolated in 2012. The MERS-CoV from the camel efficiently replicated in human cells, providing further evidence for the zoonotic potential of MERS-CoV from camels.",2014 Aug,"['Raj, V. Stalin', 'Farag, Elmoubasher A.B.A.', 'Reusken, Chantal B.E.M.', 'Lamers, Mart M.', 'Pas, Suzan D.', 'Voermans, Jolanda', 'Smits, Saskia L.', 'Osterhaus, Albert D.M.E.', 'Al-Mawlawi, Naema', 'Al-Romaihi, Hamad E.', 'AlHajri, Mohd M.', 'El-Sayed, Ahmed M.', 'Mohran, Khaled A.', 'Ghobashy, Hazem', 'Alhajri, Farhoud', 'Al-Thani, Mohamed', 'Al-Marri, Salih A.', 'El-Maghraby, Mamdouh M.', 'Koopmans, Marion P.G.', 'Haagmans, Bart L.']",Emerg Infect Dis,,,True
b8ee512613d2625710a40e986a9564b80b6057b5,PMC,"Isolation of MERS Coronavirus from a Dromedary Camel, Qatar, 2014",http://dx.doi.org/10.3201/eid2008.140663,PMC4111206,25075761,NO-CC CODE,"We obtained the full genome of Middle East respiratory syndrome coronavirus (MERS-CoV) from a camel in Qatar. This virus is highly similar to the human England/Qatar 1 virus isolated in 2012. The MERS-CoV from the camel efficiently replicated in human cells, providing further evidence for the zoonotic potential of MERS-CoV from camels.",2014 Aug,"['Raj, V. Stalin', 'Farag, Elmoubasher A.B.A.', 'Reusken, Chantal B.E.M.', 'Lamers, Mart M.', 'Pas, Suzan D.', 'Voermans, Jolanda', 'Smits, Saskia L.', 'Osterhaus, Albert D.M.E.', 'Al-Mawlawi, Naema', 'Al-Romaihi, Hamad E.', 'AlHajri, Mohd M.', 'El-Sayed, Ahmed M.', 'Mohran, Khaled A.', 'Ghobashy, Hazem', 'Alhajri, Farhoud', 'Al-Thani, Mohamed', 'Al-Marri, Salih A.', 'El-Maghraby, Mamdouh M.', 'Koopmans, Marion P.G.', 'Haagmans, Bart L.']",Emerg Infect Dis,,,False
184daf3507a842a3231c6639f3adb05539afb2d2,PMC,Interferon gamma (IFNγ) +874A/T gene polymorphism in South Indian ischemic stroke patients,http://dx.doi.org/10.5214/ans.0972.7531.1118305,PMC4116942,25205933,NO-CC CODE,"BACKGROUND: Ischemic stroke is a complex vascular and metabolic process resulting in neuronal death and progression with time. Cytokines play a role in immune response and also maintains the normal homeostatic environment of the central nervous system. IFN-γ is one of the key effector cytokines produced by NK and T cells that enhances microbicidal activity of macrophages and neutrophils. PURPOSE: As the association of IFNγ +874A/T gene polymorphism with stroke has not been investigated in Indian population, we wanted to evaluate the association of this polymorphism with ischemic stroke in a South Indian population. METHODS: We genotyped 171 ischemic stroke patients and 153 age-matched control subjects. RESULTS: Statistical analysis showed a significant association of TT homozygote with ischemic stroke (OR=1.9, 95% CI=1.05-3.43, p=0.03), while AA (OR= 0.84, 95% CI=0.54–1.31, p=0.46) and AT(OR=0.80, 95% CI=0.51-1.26, p=0.34) genotypes were not significantly associated. A and T allele frequencies in stroke were 58.78% and 41.22% as against 65.36% and 34.64% in control group, respectively, thus, suggesting no statistically significant differences in the A (OR=0.75, 95% CI=0.54–1.03, p=0.08) and T (OR=1.32, 95% CI=0.96– 1.82, p=0.08) allele frequencies between the two groups. CONCLUSION: We conclude that the IFN-γ +874 TT genotype is associated with the increased risk of ischemic stroke.",2011 Jul,"['Sultana, Shehnaz', 'Venkata, Kolla K', 'Pranay, Penagaluru K', 'Usha, Rani P', 'Reddy, P.P.']",Ann Neurosci,,,True
1b6616fe20c678e18915ea2b6fab8b22309b45b6,PMC,Successful natural interferon-β plus ribavirin therapy in a chronic hepatitis C patient after discontinuation of interferon-α treatment due to arrhythmia and interstitial pneumonia,http://dx.doi.org/10.1007/s12328-014-0500-8,PMC4124242,25132867,NO-CC CODE,"A 71-year-old female patient with hepatitis C virus genotype 1 had previously discontinued interferon (IFN)-α plus ribavirin therapy, pegylated IFN-α (pegIFN-α) monotherapy, and natural IFN-α monotherapy because of arrhythmia, interstitial pneumonia, and severe neurovegetative symptoms. She subsequently completed 72 weeks of natural IFN-β plus ribavirin therapy without remarkable adverse effects and achieved a sustained viral response, suggesting differences in the pharmacological properties and biological effects of IFN-α and IFN-β. Thus, natural IFN-β plus ribavirin therapy may be a treatment option for patients with poor tolerance to IFN-α or pegIFN-α treatments.",2014 Jun 6,"['Sato, Akira', 'Yamauchi, Masahiro', 'Yamada, Takayuki', 'Kumano, Reiko', 'Adachi, Kayo', 'Ishii, Toshiya', 'Hayashi, Mikihito', 'Kumon, Daisuke']",Clin J Gastroenterol,,,True
ab6b6eba28fd72e9bf01d2821cc00762411b6a07,PMC,A Versatile PDMS/Paper Hybrid Microfluidic Platform for Sensitive Infectious Disease Diagnosis,http://dx.doi.org/10.1021/ac5021694,PMC4144724,25019330,NO-CC CODE,"[Image: see text] Bacterial meningitis is a serious health concern worldwide. Given that meningitis can be fatal and many meningitis cases occurred in high-poverty areas, a simple, low-cost, highly sensitive method is in great need for immediate and early diagnosis of meningitis. Herein, we report a versatile and cost-effective polydimethylsiloxane (PDMS)/paper hybrid microfluidic device integrated with loop-mediated isothermal amplification (LAMP) for the rapid, sensitive, and instrument-free detection of the main meningitis-causing bacteria, Neisseria meningitidis (N. meningitidis). The introduction of paper into the microfluidic device for LAMP reactions enables stable test results over a much longer period of time than a paper-free microfluidic system. This hybrid system also offers versatile functions, by providing not only on-site qualitative diagnostic analysis (i.e., a yes or no answer), but also confirmatory testing and quantitative analysis in laboratory settings. The limit of detection of N. meningitidis is about 3 copies per LAMP zone within 45 min, close to single-bacterium detection sensitivity. In addition, we have achieved simple pathogenic microorganism detection without a laborious sample preparation process and without the use of centrifuges. This low-cost hybrid microfluidic system provides a simple and highly sensitive approach for fast instrument-free diagnosis of N. meningitidis in resource-limited settings. This versatile PDMS/paper microfluidic platform has great potential for the point of care (POC) diagnosis of a wide range of infectious diseases, especially for developing nations.",2014 Aug 5,"['Dou, Maowei', 'Dominguez, Delfina\nC.', 'Li, XiuJun', 'Sanchez, Juan', 'Scott, Gabriel']",Anal Chem,,,True
590425a9891786425ac88780f5fd37414cfb1466,PMC,A Versatile PDMS/Paper Hybrid Microfluidic Platform for Sensitive Infectious Disease Diagnosis,http://dx.doi.org/10.1021/ac5021694,PMC4144724,25019330,NO-CC CODE,"[Image: see text] Bacterial meningitis is a serious health concern worldwide. Given that meningitis can be fatal and many meningitis cases occurred in high-poverty areas, a simple, low-cost, highly sensitive method is in great need for immediate and early diagnosis of meningitis. Herein, we report a versatile and cost-effective polydimethylsiloxane (PDMS)/paper hybrid microfluidic device integrated with loop-mediated isothermal amplification (LAMP) for the rapid, sensitive, and instrument-free detection of the main meningitis-causing bacteria, Neisseria meningitidis (N. meningitidis). The introduction of paper into the microfluidic device for LAMP reactions enables stable test results over a much longer period of time than a paper-free microfluidic system. This hybrid system also offers versatile functions, by providing not only on-site qualitative diagnostic analysis (i.e., a yes or no answer), but also confirmatory testing and quantitative analysis in laboratory settings. The limit of detection of N. meningitidis is about 3 copies per LAMP zone within 45 min, close to single-bacterium detection sensitivity. In addition, we have achieved simple pathogenic microorganism detection without a laborious sample preparation process and without the use of centrifuges. This low-cost hybrid microfluidic system provides a simple and highly sensitive approach for fast instrument-free diagnosis of N. meningitidis in resource-limited settings. This versatile PDMS/paper microfluidic platform has great potential for the point of care (POC) diagnosis of a wide range of infectious diseases, especially for developing nations.",2014 Aug 5,"['Dou, Maowei', 'Dominguez, Delfina\nC.', 'Li, XiuJun', 'Sanchez, Juan', 'Scott, Gabriel']",Anal Chem,,,False
61f833b5c4fb1c5d9a82ca699af4457e93d7ab12,PMC,Sequencing and Computational Approaches to Identification and Characterization of Microbial Organisms,http://dx.doi.org/10.4137/BECB.S10886,PMC4147756,25288901,NO-CC CODE,"The recent advances in sequencing technologies and computational approaches are propelling scientists ever closer towards complete understanding of human-microbial interactions. The powerful sequencing platforms are rapidly producing huge amounts of nucleotide sequence data which are compiled into huge databases. This sequence data can be retrieved, assembled, and analyzed for identification of microbial pathogens and diagnosis of diseases. In this article, we present a commentary on how the metagenomics incorporated with microarray and new sequencing techniques are helping microbial detection and characterization.",2013 May 20,"['Yadav, Brijesh Singh', 'Ronda, Venkateswarlu', 'Vashista, Dinesh P', 'Sharma, Bhaskar']",Biomed Eng Comput Biol,,,True
b34652cd7c52b16dc961e00da7f2b64599aba91a,PMC,Membrane Interacting Regions of Dengue Virus NS2A Protein,http://dx.doi.org/10.1021/jp504911r,PMC4148155,25119664,NO-CC CODE,"[Image: see text] The Dengue virus (DENV) NS2A protein, essential for viral replication, is a poorly characterized membrane protein. NS2A displays both protein/protein and membrane/protein interactions, yet neither its functions in the viral cycle nor its active regions are known with certainty. To highlight the different membrane-active regions of NS2A, we characterized the effects of peptides derived from a peptide library encompassing this protein’s full length on different membranes by measuring their membrane leakage induction and modulation of lipid phase behavior. Following this initial screening, one region, peptide dens25, had interesting effects on membranes; therefore, we sought to thoroughly characterize this region’s interaction with membranes. This peptide presents an interfacial/hydrophobic pattern characteristic of a membrane-proximal segment. We show that dens25 strongly interacts with membranes that contain a large proportion of lipid molecules with a formal negative charge, and that this effect has a major electrostatic contribution. Considering its membrane modulating capabilities, this region might be involved in membrane rearrangements and thus be important for the viral cycle.",2014 Aug 28,"['Nemésio, Henrique', 'Villalaín, José']",J Phys Chem B,,,True
4eea77457606a86e9c391837029ab326868b9fa7,PMC,Membrane Interacting Regions of Dengue Virus NS2A Protein,http://dx.doi.org/10.1021/jp504911r,PMC4148155,25119664,NO-CC CODE,"[Image: see text] The Dengue virus (DENV) NS2A protein, essential for viral replication, is a poorly characterized membrane protein. NS2A displays both protein/protein and membrane/protein interactions, yet neither its functions in the viral cycle nor its active regions are known with certainty. To highlight the different membrane-active regions of NS2A, we characterized the effects of peptides derived from a peptide library encompassing this protein’s full length on different membranes by measuring their membrane leakage induction and modulation of lipid phase behavior. Following this initial screening, one region, peptide dens25, had interesting effects on membranes; therefore, we sought to thoroughly characterize this region’s interaction with membranes. This peptide presents an interfacial/hydrophobic pattern characteristic of a membrane-proximal segment. We show that dens25 strongly interacts with membranes that contain a large proportion of lipid molecules with a formal negative charge, and that this effect has a major electrostatic contribution. Considering its membrane modulating capabilities, this region might be involved in membrane rearrangements and thus be important for the viral cycle.",2014 Aug 28,"['Nemésio, Henrique', 'Villalaín, José']",J Phys Chem B,,,False
0aca9344d369a4d450301ff2d727e4dd5219d45b,PMC,The effect of spent bleaching earth ageing process on its physicochemical and microbial composition and its potential use as a source of fatty acids and triterpenes,http://dx.doi.org/10.1007/s11356-014-3021-6,PMC4161935,24875308,NO-CC CODE,"This study was aimed at investigating the physicochemical and microbiological changes that took place during the ageing process of spent bleaching earth in the presence of autochthonous microorganisms. Research material included fresh spent bleaching earth (SBE(0)) and the same material after 3 years of storage at the constant temperature of 20 °C, without aeration and moistening (SBE(3)). Changes in the chemical composition of analysed waste material were observed during its ageing process point to a spontaneous bioconversion of fat substance towards formation and/or release of free saturated fatty acids C16:0 and C18:0 (14.3 g 100 g(−1) D.M.), triterpenes (8.48 g 100 g(−1) D.M.), cholesterol (3.29 g 100 g(−1) D.M.), small quantities of carbohydrates and esters (0.80 g 100 g(−1) D.M.). This process was accompanied by other changes in physicochemical parameters of the waste material, such as colour, odour and viscosity, decrease in fat content from 28.27 to 24.6 % and that of soluble forms of metals (Mo, Cu, Fe, Zn, Ni, Cr and Mn), ranging from 25 to 75 %, and an increase in pH, from 3.85 to 4.2. At the same time, changes in the microbial consortium were observed.",2014 May 31,"['Krzyśko-Łupicka, Teresa', 'Cybulska, Krystyna', 'Wieczorek, Andrzej', 'Możdżer, Ewa', 'Nowak, Maciej J.']",Environ Sci Pollut Res Int,,,True
f898a667de6c7ad8916d2e542498e953589be8d7,PMC,Computer aided prediction and identification of potential epitopes in the receptor binding domain (RBD) of spike (S) glycoprotein of MERS-CoV,http://dx.doi.org/10.6026/97320630010533,PMC4166774,25258490,NO-CC CODE,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) belongs to the coronaviridae family. In spite of several outbreaks in the very recent years, no vaccine against this deadly virus is developed yet. In this study, the receptor binding domain (RBD) of Spike (S) glycoprotein of MERS-CoV was analyzed through Computational Immunology approach to identify the antigenic determinants (epitopes). In order to do so, the sequences of S glycoprotein that belong to different geographical regions were aligned to observe the conservancy of MERS-CoV RBD. The immune parameters of this region were determined using different in silico tools and Immune Epitope Database (IEDB). Molecular docking study was also employed to check the affinity of the potential epitope towards the binding cleft of the specific HLA allele. The N-terminus RBD (S367-S606) of S glycoprotein was found to be conserved among all the available strains of MERS-CoV. Based on the lower IC(50) value, a total of eight potential T-cell epitopes and 19 major histocompatibility complex (MHC) class-I alleles were identified for this conserved region. A 9-mer epitope CYSSLILDY displayed interactions with the maximum number of MHC class-I molecules and projected the highest peak in the B-cell antigenicity plot which concludes that it could be a better choice for designing an epitope based peptide vaccine against MERSCoV considering that it must undergo further in vitro and in vivo experiments. Moreover, in molecular docking study, this epitope was found to have a significant binding affinity of -8.5 kcal/mol towards the binding cleft of the HLA-C*12:03 molecule.",2014 Aug 30,"['ali, Mohammad Tuhin', 'Morshed, Mohammed Monzur', 'Gazi, Md. Amran', 'Musa, Md. Abu', 'Kibria, Md Golam', 'Uddin, Md Jashim', 'Khan, Md. Anik Ashfaq', 'Hasan, Shihab']",Bioinformation,,,True
61f8f752bb0cc577734949f8fb1f2d1f6aae7c0b,PMC,Computer aided prediction and identification of potential epitopes in the receptor binding domain (RBD) of spike (S) glycoprotein of MERS-CoV,http://dx.doi.org/10.6026/97320630010533,PMC4166774,25258490,NO-CC CODE,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) belongs to the coronaviridae family. In spite of several outbreaks in the very recent years, no vaccine against this deadly virus is developed yet. In this study, the receptor binding domain (RBD) of Spike (S) glycoprotein of MERS-CoV was analyzed through Computational Immunology approach to identify the antigenic determinants (epitopes). In order to do so, the sequences of S glycoprotein that belong to different geographical regions were aligned to observe the conservancy of MERS-CoV RBD. The immune parameters of this region were determined using different in silico tools and Immune Epitope Database (IEDB). Molecular docking study was also employed to check the affinity of the potential epitope towards the binding cleft of the specific HLA allele. The N-terminus RBD (S367-S606) of S glycoprotein was found to be conserved among all the available strains of MERS-CoV. Based on the lower IC(50) value, a total of eight potential T-cell epitopes and 19 major histocompatibility complex (MHC) class-I alleles were identified for this conserved region. A 9-mer epitope CYSSLILDY displayed interactions with the maximum number of MHC class-I molecules and projected the highest peak in the B-cell antigenicity plot which concludes that it could be a better choice for designing an epitope based peptide vaccine against MERSCoV considering that it must undergo further in vitro and in vivo experiments. Moreover, in molecular docking study, this epitope was found to have a significant binding affinity of -8.5 kcal/mol towards the binding cleft of the HLA-C*12:03 molecule.",2014 Aug 30,"['ali, Mohammad Tuhin', 'Morshed, Mohammed Monzur', 'Gazi, Md. Amran', 'Musa, Md. Abu', 'Kibria, Md Golam', 'Uddin, Md Jashim', 'Khan, Md. Anik Ashfaq', 'Hasan, Shihab']",Bioinformation,,,False
4630cc2a962fc78b5f438c4d95f9163f2ee7e189,PMC,Rapid identification of novel antigens of Salmonella Enteritidis by microarray-based immunoscreening,http://dx.doi.org/10.1007/s00604-014-1197-6,PMC4167438,25253911,NO-CC CODE,"We report on an approach to rapidly screen thousands of Salmonella Enteritidis proteins with the goal of identifying novel immunodominant proteins. We used a microarray-based system that warrants high throughput and easy handling. Seven immunogenic candidates were selected after screening. Comparative analyses by ELISA and microarrays manifested their immunodominant character. The large repetitive protein (SEN4030) that plays a role as a putative adhesin in initial cell surface interaction and is highly specific to Salmonella is considered to be the most suitable protein for a diagnostic approach. The results further demonstrate that the strategy applied herein is convenient for specifically identifying immunogenic proteins of pathogenic microorganisms. Consequently, it enables a sound assessment of promising candidates for diagnostic applications and vaccine development. Moreover, the elucidation of immunogenic proteins may assist in unveiling unknown virulence-associated factors, thus furthering the understanding of the underlying pathogenicity of Salmonella in general, and of S. Enteritidis, one of the most frequently detected serovars of this pathogen, in particular. [Figure: see text]",2014 Feb 14,"['Danckert, Lena', 'Hoppe, Sebastian', 'Bier, Frank F.', 'von Nickisch-Rosenegk, Markus']",Mikrochim Acta,,,True
8de830f756b5674df785ee18adbe375ded033a81,PMC,Multiplex isothermal solid-phase recombinase polymerase amplification for the specific and fast DNA-based detection of three bacterial pathogens,http://dx.doi.org/10.1007/s00604-014-1198-5,PMC4167443,25253912,NO-CC CODE,"We report on the development of an on-chip RPA (recombinase polymerase amplification) with simultaneous multiplex isothermal amplification and detection on a solid surface. The isothermal RPA was applied to amplify specific target sequences from the pathogens Neisseria gonorrhoeae, Salmonella enterica and methicillin-resistant Staphylococcus aureus (MRSA) using genomic DNA. Additionally, a positive plasmid control was established as an internal control. The four targets were amplified simultaneously in a quadruplex reaction. The amplicon is labeled during on-chip RPA by reverse oligonucleotide primers coupled to a fluorophore. Both amplification and spatially resolved signal generation take place on immobilized forward primers bount to expoxy-silanized glass surfaces in a pump-driven hybridization chamber. The combination of microarray technology and sensitive isothermal nucleic acid amplification at 38 °C allows for a multiparameter analysis on a rather small area. The on-chip RPA was characterized in terms of reaction time, sensitivity and inhibitory conditions. A successful enzymatic reaction is completed in <20 min and results in detection limits of 10 colony-forming units for methicillin-resistant Staphylococcus aureus and Salmonella enterica and 100 colony-forming units for Neisseria gonorrhoeae. The results show this method to be useful with respect to point-of-care testing and to enable simplified and miniaturized nucleic acid-based diagnostics. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00604-014-1198-5) contains supplementary material, which is available to authorized users.",2014 Feb 18,"['Kersting, Sebastian', 'Rausch, Valentina', 'Bier, Frank F.', 'von Nickisch-Rosenegk, Markus']",Mikrochim Acta,,,False
1489b6508e4fd548cb93f4638e640de5f2741634,PMC,Multiplex isothermal solid-phase recombinase polymerase amplification for the specific and fast DNA-based detection of three bacterial pathogens,http://dx.doi.org/10.1007/s00604-014-1198-5,PMC4167443,25253912,NO-CC CODE,"We report on the development of an on-chip RPA (recombinase polymerase amplification) with simultaneous multiplex isothermal amplification and detection on a solid surface. The isothermal RPA was applied to amplify specific target sequences from the pathogens Neisseria gonorrhoeae, Salmonella enterica and methicillin-resistant Staphylococcus aureus (MRSA) using genomic DNA. Additionally, a positive plasmid control was established as an internal control. The four targets were amplified simultaneously in a quadruplex reaction. The amplicon is labeled during on-chip RPA by reverse oligonucleotide primers coupled to a fluorophore. Both amplification and spatially resolved signal generation take place on immobilized forward primers bount to expoxy-silanized glass surfaces in a pump-driven hybridization chamber. The combination of microarray technology and sensitive isothermal nucleic acid amplification at 38 °C allows for a multiparameter analysis on a rather small area. The on-chip RPA was characterized in terms of reaction time, sensitivity and inhibitory conditions. A successful enzymatic reaction is completed in <20 min and results in detection limits of 10 colony-forming units for methicillin-resistant Staphylococcus aureus and Salmonella enterica and 100 colony-forming units for Neisseria gonorrhoeae. The results show this method to be useful with respect to point-of-care testing and to enable simplified and miniaturized nucleic acid-based diagnostics. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00604-014-1198-5) contains supplementary material, which is available to authorized users.",2014 Feb 18,"['Kersting, Sebastian', 'Rausch, Valentina', 'Bier, Frank F.', 'von Nickisch-Rosenegk, Markus']",Mikrochim Acta,,,True
3d0023b0e5f3b5a5d544abfede465a54fcf2f0bb,PMC,Pulmonary penetration of piperacillin and tazobactam in critically ill patients,http://dx.doi.org/10.1038/clpt.2014.131,PMC4169708,24926779,NO-CC CODE,"Pulmonary infections in critically ill patients are common and associated with high morbidity and mortality. Piperacillin-tazobactam is a frequently used therapy in critically ill patients with pulmonary infection. Antibiotic concentrations in the lung reflect target site antibiotic concentrations in patients with pneumonia. The aim of this study was to assess the plasma and intra-pulmonary pharmacokinetics (PK) of piperacillin-tazobactam in critically ill patients administered standard piperacillin-tazobactam regimens. A population PK model was developed to describe plasma and intra-pulmonary piperacillin and tazobactam concentrations. The probability of piperacillin exposures reaching pharmacodynamic endpoints and the impact of pulmonary permeability on piperacillin and tazobactam pulmonary penetration was explored. The median piperacillin and tazobactam pulmonary penetration ratio was 49.3% and 121.2%, respectively. Pulmonary piperacillin and tazobactam concentration were unpredictable and negatively correlated to pulmonary permeability. Current piperacillin-tazobactam regimens may be insufficient to treat pneumonia caused by piperacillin-tazobactam susceptible organisms in some critically ill patients.",2014 Oct 13,"['Felton, TW', 'McCalman, K', 'Malagon, I', 'Isalska, B', 'Whalley, S', 'Goodwin, J', 'Bentley, AM', 'Hope, WW']",Clin Pharmacol Ther,,,True
8af7d1a7c7744f3ead4f7989ef2529f75d37c16d,PMC,"Porcine Coronavirus HKU15 Detected in 9 US States, 2014",http://dx.doi.org/10.3201/eid2009.140756,PMC4178395,25153521,NO-CC CODE,,2014 Sep,"['Wang, Leyi', 'Byrum, Beverly', 'Zhang, Yan']",Emerg Infect Dis,,,True
3eb19724cbb2037dae6ea67013ae8b2edd252695,PMC,"Porcine Coronavirus HKU15 Detected in 9 US States, 2014",http://dx.doi.org/10.3201/eid2009.140756,PMC4178395,25153521,NO-CC CODE,,2014 Sep,"['Wang, Leyi', 'Byrum, Beverly', 'Zhang, Yan']",Emerg Infect Dis,,,False
1113bc8b42aace6654dc131243f78f2302bd63ba,PMC,"Novel Circovirus from Mink, China",http://dx.doi.org/10.3201/eid2009.140015,PMC4178405,25148585,NO-CC CODE,"A long-established epidemic of enteritis, caused by an unidentified pathogen distinct from parvovirus, has now been recognized in mink. In 2013, we identified a novel circovirus by degenerate PCR and fully sequenced its genome. This virus differs substantially from currently known members of the genus Circovirus and represents a new species.",2014 Sep,"['Lian, Hai', 'Liu, Ye', 'Li, Nan', 'Wang, Yuying', 'Zhang, Shoufeng', 'Hu, Rongliang']",Emerg Infect Dis,,,True
44c0a8230ff9d4468cebe29f69a0a985f5b7a4d1,PMC,Enhanced MERS Coronavirus Surveillance of Travelers from the Middle East to England,http://dx.doi.org/10.3201/eid2009.140817,PMC4178421,25148267,NO-CC CODE,"During the first year of enhanced MERS coronavirus surveillance in England, 77 persons traveling from the Middle East had acute respiratory illness and were tested for the virus. Infection was confirmed in 2 travelers with acute respiratory distress syndrome and 2 of their contacts. Patients with less severe manifestations tested negative.",2014 Sep,"['Thomas, Helen Lucy', 'Zhao, Hongxin', 'Green, Helen K.', 'Boddington, Nicola L.', 'Carvalho, Carlos F.A.', 'Osman, Husam K.', 'Sadler, Carol', 'Zambon, Maria', 'Bermingham, Alison', 'Pebody, Richard G.']",Emerg Infect Dis,,,True
a2e717e550d63d5519146d4b94fd7f71468e0a1a,PMC,"Family Cluster of Middle East Respiratory Syndrome Coronavirus Infections, Tunisia, 2013",http://dx.doi.org/10.3201/eid2009.140378,PMC4178422,25148113,NO-CC CODE,"In 2013 in Tunisia, 3 persons in 1 family were infected with Middle East respiratory syndrome coronavirus (MERS-CoV). The index case-patient’s respiratory tract samples were negative for MERS-CoV by reverse transcription PCR, but diagnosis was retrospectively confirmed by PCR of serum. Sequences clustered with those from Saudi Arabia and United Arab Emirates.",2014 Sep,"['Abroug, Fekri', 'Slim, Amine', 'Ouanes-Besbes, Lamia', 'Kacem, Mohamed-Ali Hadj', 'Dachraoui, Fahmi', 'Ouanes, Islem', 'Lu, Xiaoyan', 'Tao, Ying', 'Paden, Clinton', 'Caidi, Hayat', 'Miao, Congrong', 'Al-Hajri, Mohammed Mohammed', 'Zorraga, Mokhtar', 'Ghaouar, Wissem', 'BenSalah, Afif', 'Gerber, Susan I.', None]",Emerg Infect Dis,,,True
89e62314f07fd34f5e609e92beaa7162d28e98ea,PMC,"Family Cluster of Middle East Respiratory Syndrome Coronavirus Infections, Tunisia, 2013",http://dx.doi.org/10.3201/eid2009.140378,PMC4178422,25148113,NO-CC CODE,"In 2013 in Tunisia, 3 persons in 1 family were infected with Middle East respiratory syndrome coronavirus (MERS-CoV). The index case-patient’s respiratory tract samples were negative for MERS-CoV by reverse transcription PCR, but diagnosis was retrospectively confirmed by PCR of serum. Sequences clustered with those from Saudi Arabia and United Arab Emirates.",2014 Sep,"['Abroug, Fekri', 'Slim, Amine', 'Ouanes-Besbes, Lamia', 'Kacem, Mohamed-Ali Hadj', 'Dachraoui, Fahmi', 'Ouanes, Islem', 'Lu, Xiaoyan', 'Tao, Ying', 'Paden, Clinton', 'Caidi, Hayat', 'Miao, Congrong', 'Al-Hajri, Mohammed Mohammed', 'Zorraga, Mokhtar', 'Ghaouar, Wissem', 'BenSalah, Afif', 'Gerber, Susan I.', None]",Emerg Infect Dis,,,False
11e29fd44b612542dcb4724e582ed38d68cd93ae,PMC,"Burden of Disease, Injuries, and Risk Factors in the Kingdom of Saudi Arabia, 1990–2010",http://dx.doi.org/10.5888/pcd11.140176,PMC4184091,25275806,NO-CC CODE,"INTRODUCTION: We report the burden of disease and risk factors measured by causes of death, years of life lost attributable to premature mortality (YLLs), years of life lived with disability (YLDs), and disability-adjusted life years (DALYs) for 1990, 2005, and 2010 in the Kingdom of Saudi Arabia (KSA). METHODS: We used the Global Burden of Diseases 2010 (GBD 2010) methodology to estimate the country-level burden of disease in KSA. We used data from systematic reviews of the literature, household survey data, antenatal clinic surveillance data, reportable disease notifications, disease registries, hospital admissions data, outpatient visit data, population-based cancer registries, active screening data, and other administrative data. RESULTS: Noncommunicable diseases and road traffic injuries became the leading cause of death and disability in KSA in 2010. Elevated body mass index was the leading risk factor for disease (7.02% for males and 4.61% for females in 2010). High glucose levels were the second leading disease risk factor for females (3.28%) and third for males (6.25%) in 2010. Preterm birth complications were the main cause for DALYs in 1990; however, in 2010, the leading cause of DALYs for males was road traffic injuries (12.40%) and for females it was major depressive disorder (7.88%). CONCLUSION: KSA is facing a rising burden of noncommunicable diseases and road traffic injuries as a result of rapid changes in behaviors. Our results demonstrate the need for major intervention to reduce these burdens and to engage other sectors of the government and the community in these efforts.",2014 Oct 2,"['Memish, Ziad A.', 'Jaber, Sara', 'Mokdad, Ali H.', 'AlMazroa, Mohammad A.', 'Murray, Christopher J.L.', 'Al Rabeeah, Abdullah A.', None]",Prev Chronic Dis,,,True
aaced93f65162e95222aee866dd1248133cb4e0b,PMC,Pandemic Fear and Literature: Observations from Jack London’s The Scarlet Plague,http://dx.doi.org/10.3201/eid2010.130278,PMC4193163,25401183,NO-CC CODE,,2014 Oct,"['Riva, Michele Augusto', 'Benedetti, Marta', 'Cesana, Giancarlo']",Emerg Infect Dis,,,True
6c0943194d78de26d9019179760b3ee9ea77fab3,PMC,"Evidence of Recombinant Strains of Porcine Epidemic Diarrhea Virus, United States, 2013",http://dx.doi.org/10.3201/eid2010.140338,PMC4193173,25272273,NO-CC CODE,"To investigate the evolutionary process by which porcine epidemic diarrhea virus (PEDV) in the United States hypothetically descended from strains in China, we analyzed PEDV-positive samples collected in China during January 2012–July 2013. Recombination in 2 strain sublineages was likely associated with identification of PEDV in the United States in 2013.",2014 Oct,"['Tian, Peng-Fei', 'Jin, Yu-Lan', 'Xing, Gang', 'Qv, Ling-Ling', 'Huang, Yao-Wei', 'Zhou, Ji-Yong']",Emerg Infect Dis,,,True
3eb3d0dca624ef9014b06247bbc7e25179931647,PMC,"Evidence of Recombinant Strains of Porcine Epidemic Diarrhea Virus, United States, 2013",http://dx.doi.org/10.3201/eid2010.140338,PMC4193173,25272273,NO-CC CODE,"To investigate the evolutionary process by which porcine epidemic diarrhea virus (PEDV) in the United States hypothetically descended from strains in China, we analyzed PEDV-positive samples collected in China during January 2012–July 2013. Recombination in 2 strain sublineages was likely associated with identification of PEDV in the United States in 2013.",2014 Oct,"['Tian, Peng-Fei', 'Jin, Yu-Lan', 'Xing, Gang', 'Qv, Ling-Ling', 'Huang, Yao-Wei', 'Zhou, Ji-Yong']",Emerg Infect Dis,,,False
351fca8e4bd7321d75ec0227794deb0db3567540,PMC,"Distinct Characteristics and Complex Evolution of PEDV Strains, North America, May 2013–February 2014",http://dx.doi.org/10.3201/eid2010.140491,PMC4193278,25279722,NO-CC CODE,"Porcine epidemic diarrhea virus (PEDV), which emerged in the United States in 2013, has spread throughout North America. Limited availability of PEDV complete genomes worldwide has impeded our understanding of PEDV introduction into the United States. To determine the relationship between the North American strains and global emerging and historic PEDV strains, we sequenced and analyzed complete genomes of 74 strains from North America; the strains clustered into 2 distinct clades. Compared with the initially reported virulent US PEDV strains, 7 (9.7%) strains from 4 states contained insertions and deletions in the spike gene (S INDELs). These S INDEL strains share 99.8%–100% nt identity with each other and 96.2%–96.7% nt identity with the initial US strains. Furthermore, the S INDEL strains form a distinct cluster within North American clade II, sharing 98.6%–100% nt identity overall. In the United States, the S INDEL and original PEDV strains are co-circulating and could have been introduced simultaneously.",2014 Oct,"['Vlasova, Anastasia N.', 'Marthaler, Douglas', 'Wang, Qiuhong', 'Culhane, Marie R.', 'Rossow, Kurt D.', 'Rovira, Albert', 'Collins, James', 'Saif, Linda J.']",Emerg Infect Dis,,,True
f8a3e1444dc1b8bdd31b49ce2435d8c1b5b3d083,PMC,"Distinct Characteristics and Complex Evolution of PEDV Strains, North America, May 2013–February 2014",http://dx.doi.org/10.3201/eid2010.140491,PMC4193278,25279722,NO-CC CODE,"Porcine epidemic diarrhea virus (PEDV), which emerged in the United States in 2013, has spread throughout North America. Limited availability of PEDV complete genomes worldwide has impeded our understanding of PEDV introduction into the United States. To determine the relationship between the North American strains and global emerging and historic PEDV strains, we sequenced and analyzed complete genomes of 74 strains from North America; the strains clustered into 2 distinct clades. Compared with the initially reported virulent US PEDV strains, 7 (9.7%) strains from 4 states contained insertions and deletions in the spike gene (S INDELs). These S INDEL strains share 99.8%–100% nt identity with each other and 96.2%–96.7% nt identity with the initial US strains. Furthermore, the S INDEL strains form a distinct cluster within North American clade II, sharing 98.6%–100% nt identity overall. In the United States, the S INDEL and original PEDV strains are co-circulating and could have been introduced simultaneously.",2014 Oct,"['Vlasova, Anastasia N.', 'Marthaler, Douglas', 'Wang, Qiuhong', 'Culhane, Marie R.', 'Rossow, Kurt D.', 'Rovira, Albert', 'Collins, James', 'Saif, Linda J.']",Emerg Infect Dis,,,False
87390d2ae28407b3e03e60a6b24a7fd99ed7229a,PMC,Pro/con clinical debate: Steroids are a key component in the treatment of SARS,http://dx.doi.org/10.1186/cc2452,PMC420028,15025770,NO-CC CODE,"SARS (severe acute respiratory syndrome) proved an enormous physical and emotional challenge to frontline health care workers throughout the world in late 2002 through to mid 2003. A large percentage of patients (many being health care workers themselves) became critically ill. Unfortunately, clinicians caring for these individuals did not have the advantage of previous experience or research data on which to base treatment decisions. As a result, at least early in the outbreak, a 'best guess approach' and/or anecdotes drove therapy. In many centres systemic steroids, which carry many potential downsides, became a mainstay of therapy. In this issue of Critical Care, two groups that have frontline experience of SARS debate the role of steroids. Let us hope and pray together that we never have the patient population needed to resolve the questions the two sides raise.",2004 Jan 26,"['Gomersall, Charles D', 'Kargel, Marcus J', 'Lapinsky, Stephen E']",Crit Care,,,True
c5131e5f5c6000ec84139edc64778a6f1d391b83,PMC,"8th Annual Toronto Critical Care Medicine Symposium, 30 October–1 November 2003, Toronto, Ontario, Canada",http://dx.doi.org/10.1186/cc2429,PMC420071,14975048,NO-CC CODE,,2004 Jan 2,"['Granton, Jeff', 'Granton, John']",Crit Care,,,True
8a7d5de5ea680e784ab2bd877240bf09e4c1c02d,PMC,Recently published papers: all the usual suspects and carbon dioxide,http://dx.doi.org/10.1186/cc2449,PMC420074,14975037,NO-CC CODE,,2004 Jan 2,"Ball, Jonathan",Crit Care,,,True
c35f1a6432bd9d7f5bce38e59661f93b1aa13060,PMC,Synthetic Antibodies with a Human Framework That Protect Mice from Lethal Sudan Ebolavirus Challenge,http://dx.doi.org/10.1021/cb5006454,PMC4201348,25140871,NO-CC CODE,"[Image: see text] The ebolaviruses cause severe and rapidly progressing hemorrhagic fever. There are five ebolavirus species; although much is known about Zaire ebolavirus (EBOV) and its neutralization by antibodies, little is known about Sudan ebolavirus (SUDV), which is emerging with increasing frequency. Here we describe monoclonal antibodies containing a human framework that potently inhibit infection by SUDV and protect mice from lethal challenge. The murine antibody 16F6, which binds the SUDV envelope glycoprotein (GP), served as the starting point for design. Sequence and structural alignment revealed similarities between 16F6 and YADS1, a synthetic antibody with a humanized scaffold. A focused phage library was constructed and screened to impart 16F6-like recognition properties onto the YADS1 scaffold. A panel of 17 antibodies were characterized and found to have a range of neutralization potentials against a pseudotype virus infection model. Neutralization correlated with GP binding as determined by ELISA. Two of these clones, E10 and F4, potently inhibited authentic SUDV and conferred protection and memory immunity in mice from lethal SUDV challenge. E10 and F4 were further shown to bind to the same epitope on GP as 16F6 with comparable affinities. These antibodies represent strong immunotherapeutic candidates for treatment of SUDV infection.",2014 Oct 17,"['Chen, Gang', 'Koellhoffer, Jayne F.', 'Zak, Samantha\nE.', 'Frei, Julia C.', 'Liu, Nina', 'Long, Hua', 'Ye, Wei', 'Nagar, Kaajal', 'Pan, Guohua', 'Chandran, Kartik', 'Dye, John M.', 'Sidhu, Sachdev S.', 'Lai, Jonathan R.']",ACS Chem Biol,,,True
d67640da9a65493bdc6c39501c483b723c722fcb,PMC,Synthetic Antibodies with a Human Framework That Protect Mice from Lethal Sudan Ebolavirus Challenge,http://dx.doi.org/10.1021/cb5006454,PMC4201348,25140871,NO-CC CODE,"[Image: see text] The ebolaviruses cause severe and rapidly progressing hemorrhagic fever. There are five ebolavirus species; although much is known about Zaire ebolavirus (EBOV) and its neutralization by antibodies, little is known about Sudan ebolavirus (SUDV), which is emerging with increasing frequency. Here we describe monoclonal antibodies containing a human framework that potently inhibit infection by SUDV and protect mice from lethal challenge. The murine antibody 16F6, which binds the SUDV envelope glycoprotein (GP), served as the starting point for design. Sequence and structural alignment revealed similarities between 16F6 and YADS1, a synthetic antibody with a humanized scaffold. A focused phage library was constructed and screened to impart 16F6-like recognition properties onto the YADS1 scaffold. A panel of 17 antibodies were characterized and found to have a range of neutralization potentials against a pseudotype virus infection model. Neutralization correlated with GP binding as determined by ELISA. Two of these clones, E10 and F4, potently inhibited authentic SUDV and conferred protection and memory immunity in mice from lethal SUDV challenge. E10 and F4 were further shown to bind to the same epitope on GP as 16F6 with comparable affinities. These antibodies represent strong immunotherapeutic candidates for treatment of SUDV infection.",2014 Oct 17,"['Chen, Gang', 'Koellhoffer, Jayne F.', 'Zak, Samantha\nE.', 'Frei, Julia C.', 'Liu, Nina', 'Long, Hua', 'Ye, Wei', 'Nagar, Kaajal', 'Pan, Guohua', 'Chandran, Kartik', 'Dye, John M.', 'Sidhu, Sachdev S.', 'Lai, Jonathan R.']",ACS Chem Biol,,,False
9d97b122ebffbbf28052287cae39cd6c6d3d7cb6,PMC,Antiviral activity of a Bacillus sp. P34 peptide against pathogenic viruses of domestic animals,,PMC4204951,25477947,NO-CC CODE,"P34 is an antimicrobial peptide produced by a Bacillus sp. strain isolated from the intestinal contents of a fish in the Brazilian Amazon basin with reported antibacterial activity. The aim of this work was to evaluate the peptide P34 for its in vitro antiviral properties against canine adenovirus type 2 (CAV-2), canine coronavirus (CCoV), canine distemper virus (CDV), canine parvovirus type 2 (CPV-2), equine arteritis virus (EAV), equine influenza virus (EIV), feline calicivirus (FCV) and feline herpesvirus type 1 (FHV-1). The results showed that the peptide P34 exhibited antiviral activity against EAV and FHV-1. The peptide P34 inhibited the replication of EAV by 99.9% and FHV-1 by 94.4%. Virucidal activity was detected only against EAV. When P34 and EAV were incubated for 6 h at 37 °C the viral titer reduced from 10(4.5) TCID(50) to 10(2.75) TCID(50), showing a percent of inhibition of 98.6%. In conclusion, our results demonstrated that P34 inhibited EAV and FHV-1 replication in infected cell cultures and it showed virucidal activity against EAV. Since there is documented resistance to the current drugs used against herpesviruses and there is no treatment for equine viral arteritis, it is advisable to search for new antiviral compounds to overcome these infections.",2014 Oct 9,"['Silva, Débora Scopel e', 'de Castro, Clarissa Caetano', 'Silva, Fábio da Silva e', 'Sant’anna, Voltaire', 'Vargas, Gilberto D’Avila', 'de Lima, Marcelo', 'Fischer, Geferson', 'Brandelli, Adriano', 'da Motta, Amanda de Souza', 'Hübner, Silvia de Oliveira']",Braz J Microbiol,,,True
68816a089550c8de2cf3e05e3ae31238554cfa99,PMC,B cell homeostasis and follicle confines are governed by fibroblastic reticular cells,http://dx.doi.org/10.1038/ni.2965,PMC4205585,25151489,NO-CC CODE,"Fibroblastic reticular cells (FRCs) are known to inhabit T cell-rich areas of lymphoid organs where they function to coordinate T cell and dendritic cell interactions. However, in vivo manipulation of FRCs has been limited by a dearth of genetic tools targeting this lineage. Here, using a mouse model to conditionally ablate FRCs, we demonstrate their indispensable role in anti-viral T cell responses. Unexpectedly, FRC loss also attenuated humoral immunity due to impaired B cell viability and follicular organization. Follicle-resident FRCs established a favorable niche for B lymphocytes via production of the cytokine BAFF. Thus, our study indicates that adaptive immunity requires an intact FRC network and illuminates a subset of FRCs that controls B cell homeostasis and follicle identity.",2014 Oct 24,"['Cremasco, Viviana', 'Woodruff, Matthew C.', 'Onder, Lucas', 'Cupovic, Jovana', 'Nieves-Bonilla, Janice M.', 'Schildberg, Frank A.', 'Chang, Jonathan', 'Cremasco, Floriana', 'Harvey, Christopher J.', 'Wucherpfennig, Kai', 'Ludewig, Burkhard', 'Carroll, Michael C.', 'Turley, Shannon J.']",Nat Immunol,,,True
a67212b1e5d4cac7cd2deb4a3b065e7aac6d8aea,PMC,The Global Outbreak Alert and Response Network,http://dx.doi.org/10.1080/17441692.2014.951870,PMC4205922,25186571,NO-CC CODE,"The Global Outbreak Alert and Response Network (GOARN) was established in 2000 as a network of technical institutions, research institutes, universities, international health organisations and technical networks willing to contribute and participate in internationally coordinated responses to infectious disease outbreaks. It reflected a recognition of the need to strengthen and coordinate rapid mobilisation of experts in responding to international outbreaks and to overcome the sometimes chaotic and fragmented operations characterising previous responses. The network partners agreed that the World Health Organization would coordinate the network and provide a secretariat, which would also function as the operational support team. The network has evolved to comprise 153 institutions/technical partners and 37 additional networks, the latter encompassing a further 355 members and has been directly involved in 137 missions to 79 countries, territories or areas. Future challenges will include supporting countries to achieve the capacity to detect and respond to outbreaks of international concern, as required by the International Health Regulations (2005). GOARN's increasing regional focus and expanding geographic composition will be central to meeting these challenges. The paper summarises some of network's achievements over the past 13 years and presents some of the future challenges.",2014 Oct 21,"['Mackenzie, John S.', 'Drury, Patrick', 'Arthur, Ray R.', 'Ryan, Michael J.', 'Grein, Thomas', 'Slattery, Raphael', 'Suri, Sameera', 'Domingo, Christine Tiffany', 'Bejtullahu, Armand']",Glob Public Health,,,True
f82887cb4851069ac9a0eebd39ecda541dbd44d4,PMC,Common and unique features of viral RNA-dependent polymerases,http://dx.doi.org/10.1007/s00018-014-1695-z,PMC4207942,25080879,NO-CC CODE,"Eukaryotes and bacteria can be infected with a wide variety of RNA viruses. On average, these pathogens share little sequence similarity and use different replication and transcription strategies. Nevertheless, the members of nearly all RNA virus families depend on the activity of a virally encoded RNA-dependent polymerase for the condensation of nucleotide triphosphates. This review provides an overview of our current understanding of the viral RNA-dependent polymerase structure and the biochemistry and biophysics that is involved in replicating and transcribing the genetic material of RNA viruses.",2014 Aug 1,"te Velthuis, Aartjan J. W.",Cell Mol Life Sci,,,True
e1f1806e2d4561bb8cd2f4025586b9b6278e5a72,PMC,Functional ultrastructure of the plant nucleolus,http://dx.doi.org/10.1007/s00709-014-0648-6,PMC4209244,24756369,NO-CC CODE,"Nucleoli are nuclear domains present in almost all eukaryotic cells. They not only specialize in the production of ribosomal subunits but also play roles in many fundamental cellular activities. Concerning ribosome biosynthesis, particular stages of this process, i.e., ribosomal DNA transcription, primary RNA transcript processing, and ribosome assembly proceed in precisely defined nucleolar subdomains. Although eukaryotic nucleoli are conservative in respect of their main function, clear morphological differences between these structures can be noticed between individual kingdoms. In most cases, a plant nucleolus shows well-ordered structure in which four main ultrastructural components can be distinguished: fibrillar centers, dense fibrillar component, granular component, and nucleolar vacuoles. Nucleolar chromatin is an additional crucial structural component of this organelle. Nucleolonema, although it is not always an unequivocally distinguished nucleolar domain, has often been described as a well-grounded morphological element, especially of plant nucleoli. The ratios and morphology of particular subcompartments of a nucleolus can change depending on its metabolic activity which in turn is correlated with the physiological state of a cell, cell type, cell cycle phase, as well as with environmental influence. Precise attribution of functions to particular nucleolar subregions in the process of ribosome biosynthesis is now possible using various approaches. The presented description of plant nucleolar morphology summarizes previous knowledge regarding the function of nucleoli as well as of their particular subdomains not only in the course of ribosome biosynthesis.",2014 Apr 23,"Stępiński, Dariusz",Protoplasma,,,True
1e3e37bcaf9a7cb93acef49776b6c3dead54c430,PMC,"Nosocomial Neonatal Legionellosis Associated with Water in Infant Formula, Taiwan",http://dx.doi.org/10.3201/eid2011.140542,PMC4214307,25340315,NO-CC CODE,We report 2 cases of neonatal Legionella infection associated with aspiration of contaminated water used in hospitals to make infant formula. The molecular profiles of Legionella strains isolated from samples from the infants and from water dispensers were indistinguishable. Our report highlights the need to consider nosocomial legionellosis among neonates who have respiratory symptoms.,2014 Nov,"['Wei, Sung-Hsi', 'Chou, Pesus', 'Tseng, Lei-Ron', 'Lin, Hung-Chih', 'Wang, Jen-Hsien', 'Sheu, Ji-Nan', 'Liu, Ming-Tsan', 'Liu, Fang-Ching', 'Wu, Hoa-Hsin', 'Lin, Min-Cheng', 'Ko, Ching-Fen', 'Lin, Hsiang-Yu', 'Kao, Pei-Hsiu', 'Hwang, Kao-Pin', 'Hsu, Yu-Lung', 'Kuo, Tsung-Lin', 'Chiang, Chuen-Sheue']",Emerg Infect Dis,,,True
4b4a95851bb68a1519d856046d011c084ed8eca6,PMC,Respiratory Viruses and Bacteria among Pilgrims during the 2013 Hajj,http://dx.doi.org/10.3201/eid2011.140600,PMC4214309,25341199,NO-CC CODE,"Pilgrims returning from the Hajj might contribute to international spreading of respiratory pathogens. Nasal and throat swab specimens were obtained from 129 pilgrims in 2013 before they departed from France and before they left Saudi Arabia, and tested by PCR for respiratory viruses and bacteria. Overall, 21.5% and 38.8% of pre-Hajj and post-Hajj specimens, respectively, were positive for ≥1 virus (p = 0.003). One third (29.8%) of the participants acquired ≥1 virus, particularly rhinovirus (14.0%), coronavirus E229 (12.4%), and influenza A(H3N2) virus (6.2%) while in Saudi Arabia. None of the participants were positive for the Middle East respiratory syndrome coronavirus. In addition, 50.0% and 62.0% of pre-Hajj and post-Hajj specimens, respectively, were positive for Streptococcus pneumoniae (p = 0.053). One third (36.3%) of the participants had acquired S. pneumoniae during their stay. Our results confirm high acquisition rates of rhinovirus and S. pneumoniae in pilgrims and highlight the acquisition of coronavirus E229.",2014 Nov,"['Benkouiten, Samir', 'Charrel, Rémi', 'Belhouchat, Khadidja', 'Drali, Tassadit', 'Nougairede, Antoine', 'Salez, Nicolas', 'Memish, Ziad A.', 'al Masri, Malak', 'Fournier, Pierre-Edouard', 'Raoult, Didier', 'Brouqui, Philippe', 'Parola, Philippe', 'Gautret, Philippe']",Emerg Infect Dis,,,True
e4b48ce0579f908da6dd3289bb2cc262dbdeae72,PMC,Detection of hepatitis C virus in the nasal secretions of an intranasal drug-user,http://dx.doi.org/10.1186/1476-0711-3-6,PMC421742,15132748,NO-CC CODE,"BACKGROUND: One controversial source of infection for hepatitis C virus (HCV) involves the sharing of contaminated implements, such as straws or spoons, used to nasally inhale cocaine and other powdered drugs. An essential precondition for this mode of transmission is the presence of HCV in the nasal secretions of intranasal drug users. METHODS: Blood and nasal secretion samples were collected from five plasma-positive chronic intranasal drug users and tested for HCV RNA using RT-PCR. RESULTS: HCV was detected in all five blood samples and in the nasal secretions of the subject with the highest serum viral load. CONCLUSIONS: This study is the first to demonstrate the presence of HCV in nasal secretions. This finding has implications for potential transmission of HCV through contact with contaminated nasal secretions.",2004 May 7,"['McMahon, James M', 'Simm, Malgorzata', 'Milano, Danielle', 'Clatts, Michael']",Ann Clin Microbiol Antimicrob,,,True
766398b576402973f5fe2e2e5b0c5a9d6017b0c0,PMC,"Public Health in Big Cities: Looking Back, Looking Forward",http://dx.doi.org/10.1097/PHH.0000000000000134,PMC4243799,25423052,NO-CC CODE,"This commentary provides reflections of a public health official on the important role public health departments play in advancing the goals of the larger public health enterprise in big cities, counties, and large metropolitan areas.",2015 Jan 20,"Fielding, Jonathan E.",J Public Health Manag Pract,,,True
22212b4c01be73b039da9396b7d20fb4a3429cb5,PMC,"Associations of IFN-γ rs2430561 T/A, IL28B rs12979860 C/T and ERα rs2077647 T/C polymorphisms with outcomes of hepatitis B virus infection: a meta-analysis",http://dx.doi.org/10.7555/JBR.28.20130162,PMC4250527,25469118,NO-CC CODE,"Several studies investigated associations of IFN-γ rs2430561 T/A, IL28B rs12979860 C/T and ERα rs2077647 T/C gene polymorphisms with outcomes of hepatitis B virus (HBV) infection, but the results were controversial. Therefore, we performed a meta-analysis of all published observational studies to address this inconsistency. Literature was searched in online database and a systematic review was conducted based on the search results. A total of 24 studies were included and dichotomous data were presented as odds ratio (OR) with a 95% confidence interval (CI). The rs2430561 T allele was associated with reduced persistent HBV infection risk (T vs. A: OR, 0.690; 95% CI, [0.490, 0.971]), while the rs2077647 T allele significantly increased the risk of persistent HBV infection (T vs. C: OR, 1.678; 95% CI, [1.212, 2.323]). Rs 2077647 CC might play a role in protecting individuals against HBV persistence (TT vs. CC: OR, 4.109; 95% CI, [2.609, 6.473]). Furthermore, carriers of the rs2430561 TT genotype were more likely to clear HBV spontaneously compared with those of the AA genotype (TT vs. AA: OR, 0.555; 95% CI, [0.359, 0.856]). For rs12979860 C/T polymorphism, no significant correlation with HBV infection outcomes was found. In subgroup analyses, the results were similar to those of overall analysis. However, for rs2077647 TT vs. TC+CC, significantly increased risks were observed in the Asian and hospital-based population, but not in the overall analysis. IFN-γ rs2430561 T/A and ERα rs2077647 T/C genetic polymorphisms were associated with outcomes of HBV infection, but no association was found between IL28B rs12979860 C/T and HBV infection.",2014 Nov 10,"['Tang, Shaidi', 'Yue, Ming', 'Wang, Jiajia', 'Zhang, Yun', 'Yu, Rongbin', 'Su, Jing', 'Peng, Zhihang', 'Wang, Jie']",J Biomed Res,,,True
b19c7828106ac7bcff5511ee3fc7189123e0cc4c,PMC,"Health Care Worker Contact with MERS Patient, Saudi Arabia",http://dx.doi.org/10.3201/eid2012.141211,PMC4257796,25418612,NO-CC CODE,"To investigate potential transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) to health care workers in a hospital, we serologically tested hospital contacts of the index case-patient in Saudi Arabia, 4 months after his death. None of the 48 contacts showed evidence of MERS-CoV infection.",2014 Dec,"['Hall, Aron J.', 'Tokars, Jerome I.', 'Badreddine, Samar A.', 'Saad, Ziad Bin', 'Furukawa, Elaine', 'Al Masri, Malak', 'Haynes, Lia M.', 'Gerber, Susan I.', 'Kuhar, David T.', 'Miao, Congrong', 'Trivedi, Suvang U.', 'Pallansch, Mark A.', 'Hajjeh, Rana', 'Memish, Ziad A.']",Emerg Infect Dis,,,True
4e38e3ba046eee2b6581520ef5e4f33ec8168bb4,PMC,"Human Infection with Influenza Virus A(H10N8) from Live Poultry Markets, China, 2014",http://dx.doi.org/10.3201/eid2012.140911,PMC4257803,25425075,NO-CC CODE,Human infection with avian influenza virus A(H10N8) was initially reported in China in December 2013. We characterized H10N8 strains from a human patient and from poultry in live markets that infected persons had visited. Results of genome sequencing and virus characterization suggest that the virus strains that infected humans originated from these markets.,2014 Dec,"['Zhang, Tao', 'Bi, Yuhai', 'Tian, Huaiyu', 'Li, Xiaowen', 'Liu, Di', 'Wu, Ying', 'Jin, Tao', 'Wang, Yong', 'Chen, Quanjiao', 'Chen, Ze', 'Chang, Jianyu', 'Gao, George F.', 'Xu, Bing']",Emerg Infect Dis,,,True
92c3491310afbd2b13368d1e64b5e46ac71934bf,PMC,"Equine Influenza A(H3N8) Virus Isolated from Bactrian Camel, Mongolia",http://dx.doi.org/10.3201/eid2012.140435,PMC4257804,25418532,NO-CC CODE,"Because little is known about the ecology of influenza viruses in camels, 460 nasal swab specimens were collected from healthy (no overt illness) Bactrian camels in Mongolia during 2012. One specimen was positive for influenza A virus (A/camel/Mongolia/335/2012[H3N8]), which is phylogenetically related to equine influenza A(H3N8) viruses and probably represents natural horse-to-camel transmission.",2014 Dec,"['Yondon, Myagmarsukh', 'Zayat, Batsukh', 'Nelson, Martha I.', 'Heil, Gary L.', 'Anderson, Benjamin D.', 'Lin, Xudong', 'Halpin, Rebecca A.', 'McKenzie, Pamela P.', 'White, Sarah K.', 'Wentworth, David E.', 'Gray, Gregory C.']",Emerg Infect Dis,,,True
064b8b054101863fcb0905b3926ed4f5531dceda,PMC,"Equine Influenza A(H3N8) Virus Isolated from Bactrian Camel, Mongolia",http://dx.doi.org/10.3201/eid2012.140435,PMC4257804,25418532,NO-CC CODE,"Because little is known about the ecology of influenza viruses in camels, 460 nasal swab specimens were collected from healthy (no overt illness) Bactrian camels in Mongolia during 2012. One specimen was positive for influenza A virus (A/camel/Mongolia/335/2012[H3N8]), which is phylogenetically related to equine influenza A(H3N8) viruses and probably represents natural horse-to-camel transmission.",2014 Dec,"['Yondon, Myagmarsukh', 'Zayat, Batsukh', 'Nelson, Martha I.', 'Heil, Gary L.', 'Anderson, Benjamin D.', 'Lin, Xudong', 'Halpin, Rebecca A.', 'McKenzie, Pamela P.', 'White, Sarah K.', 'Wentworth, David E.', 'Gray, Gregory C.']",Emerg Infect Dis,,,False
1c1c1e38bc3c71b4b634b86998ed2e12be6c89de,PMC,"Novel Porcine Epidemic Diarrhea Virus Variant with Large Genomic Deletion, South Korea",http://dx.doi.org/10.3201/eid2012.131642,PMC4257805,25424875,NO-CC CODE,"Since 1992, porcine epidemic diarrhea virus (PEDV) has been one of the most common porcine diarrhea–associated viruses in South Korea. We conducted a large-scale investigation of the incidence of PEDV in pigs with diarrhea in South Korea and consequently identified and characterized a novel PEDV variant with a large genomic deletion.",2014 Dec,"['Park, Seongjun', 'Kim, Sanghyun', 'Song, Daesub', 'Park, Bongkyun']",Emerg Infect Dis,,,True
dc37b885f85c99c777d87658f2194b71e17c237e,PMC,"Novel Porcine Epidemic Diarrhea Virus Variant with Large Genomic Deletion, South Korea",http://dx.doi.org/10.3201/eid2012.131642,PMC4257805,25424875,NO-CC CODE,"Since 1992, porcine epidemic diarrhea virus (PEDV) has been one of the most common porcine diarrhea–associated viruses in South Korea. We conducted a large-scale investigation of the incidence of PEDV in pigs with diarrhea in South Korea and consequently identified and characterized a novel PEDV variant with a large genomic deletion.",2014 Dec,"['Park, Seongjun', 'Kim, Sanghyun', 'Song, Daesub', 'Park, Bongkyun']",Emerg Infect Dis,,,False
e4c93a18d68cdabdab5f1ed3ba9621f611f3aa9e,PMC,"Third Strain of Porcine Epidemic Diarrhea Virus, United States",http://dx.doi.org/10.3201/eid2014.140908,PMC4257813,25417647,NO-CC CODE,,2014 Dec,"['Marthaler, Douglas', 'Bruner, Laura', 'Collins, James', 'Rossow, Kurt']",Emerg Infect Dis,,,True
74ae352ed6606527cca17ab3b773687251f38590,PMC,Replication and Shedding of MERS-CoV in Upper Respiratory Tract of Inoculated Dromedary Camels,http://dx.doi.org/10.3201/eid2012.141280,PMC4257817,25418529,NO-CC CODE,"In 2012, a novel coronavirus associated with severe respiratory disease in humans emerged in the Middle East. Epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of Middle East respiratory syndrome coronavirus (MERS-CoV). Here we provide experimental support for camels as a reservoir for MERS-CoV. We inoculated 3 adult camels with a human isolate of MERS-CoV and a transient, primarily upper respiratory tract infection developed in each of the 3 animals. Clinical signs of the MERS-CoV infection were benign, but each of the camels shed large quantities of virus from the upper respiratory tract. We detected infectious virus in nasal secretions through 7 days postinoculation, and viral RNA up to 35 days postinoculation. The pattern of shedding and propensity for the upper respiratory tract infection in dromedary camels may help explain the lack of systemic illness among naturally infected camels and the means of efficient camel-to-camel and camel-to-human transmission.",2014 Dec,"['Adney, Danielle R.', 'van Doremalen, Neeltje', 'Brown, Vienna R.', 'Bushmaker, Trenton', 'Scott, Dana', 'de Wit, Emmie', 'Bowen, Richard A.', 'Munster, Vincent J.']",Emerg Infect Dis,,,True
9ea9c0517c3f57dd4eeab9d0b6bb64f785ce36dc,PMC,"MERS Coronavirus Neutralizing Antibodies in Camels, Eastern Africa, 1983–1997",http://dx.doi.org/10.3201/eid2012.141026,PMC4257824,25425139,NO-CC CODE,"To analyze the distribution of Middle East respiratory syndrome coronavirus (MERS-CoV)–seropositive dromedary camels in eastern Africa, we tested 189 archived serum samples accumulated during the past 30 years. We identified MERS-CoV neutralizing antibodies in 81.0% of samples from the main camel-exporting countries, Sudan and Somalia, suggesting long-term virus circulation in these animals.",2014 Dec,"['Müller, Marcel A.', 'Corman, Victor Max', 'Jores, Joerg', 'Meyer, Benjamin', 'Younan, Mario', 'Liljander, Anne', 'Bosch, Berend-Jan', 'Lattwein, Erik', 'Hilali, Mosaad', 'Musa, Bakri E.', 'Bornstein, Set', 'Drosten, Christian']",Emerg Infect Dis,,,True
b745433cc7835b93e2aa9e87e44a4f1658523a41,PMC,"MERS Coronavirus Neutralizing Antibodies in Camels, Eastern Africa, 1983–1997",http://dx.doi.org/10.3201/eid2012.141026,PMC4257824,25425139,NO-CC CODE,"To analyze the distribution of Middle East respiratory syndrome coronavirus (MERS-CoV)–seropositive dromedary camels in eastern Africa, we tested 189 archived serum samples accumulated during the past 30 years. We identified MERS-CoV neutralizing antibodies in 81.0% of samples from the main camel-exporting countries, Sudan and Somalia, suggesting long-term virus circulation in these animals.",2014 Dec,"['Müller, Marcel A.', 'Corman, Victor Max', 'Jores, Joerg', 'Meyer, Benjamin', 'Younan, Mario', 'Liljander, Anne', 'Bosch, Berend-Jan', 'Lattwein, Erik', 'Hilali, Mosaad', 'Musa, Bakri E.', 'Bornstein, Set', 'Drosten, Christian']",Emerg Infect Dis,,,False
3b8be6719d642862ae96fc5614e4f555c38f2af2,PMC,Coronavirus membrane-associated papain-like proteases induce autophagy through interacting with Beclin1 to negatively regulate antiviral innate immunity,http://dx.doi.org/10.1007/s13238-014-0104-6,PMC4259884,25311841,NO-CC CODE,"Autophagy plays important roles in modulating viral replication and antiviral immune response. Coronavirus infection is associated with the autophagic process, however, little is known about the mechanisms of autophagy induction and its contribution to coronavirus regulation of host innate responses. Here, we show that the membrane-associated papain-like protease PLP2 (PLP2-TM) of coronaviruses acts as a novel autophagy-inducing protein. Intriguingly, PLP2-TM induces incomplete autophagy process by increasing the accumulation of autophagosomes but blocking the fusion of autophagosomes with lysosomes. Furthermore, PLP2-TM interacts with the key autophagy regulators, LC3 and Beclin1, and promotes Beclin1 interaction with STING, the key regulator for antiviral IFN signaling. Finally, knockdown of Beclin1 partially reverses PLP2-TM’s inhibitory effect on innate immunity which resulting in decreased coronavirus replication. These results suggested that coronavirus papain-like protease induces incomplete autophagy by interacting with Beclin1, which in turn modulates coronavirus replication and antiviral innate immunity.",2014 Dec 15,"['Chen, Xiaojuan', 'Wang, Kai', 'Xing, Yaling', 'Tu, Jian', 'Yang, Xingxing', 'Zhao, Qian', 'Li, Kui', 'Chen, Zhongbin']",Protein Cell,,,True
983154b0c824acdd8a9acf1e6ab1c9fe03c392f3,PMC,Insights into Ebola and Other Emerging and Re-emerging Infectious Disease Risks,http://dx.doi.org/10.4137/EHI.S20757,PMC4267510,25535455,NO-CC CODE,,2014 Oct 29,"Kelley, Timothy R",Environ Health Insights,,,True
494b65b83c62d007f6ebd38d7ae83516a8fd6971,PMC,Structural Insights into 5' Flap DNA Unwinding and Incision by the Human FAN1 Dimer,http://dx.doi.org/10.1038/ncomms6726,PMC4268874,25500724,NO-CC CODE,"Human FANCD2-associated nuclease 1 (FAN1) is a DNA structure-specific nuclease involved in the processing of DNA interstrand crosslinks (ICLs). FAN1 maintains genomic stability and prevents tissue decline in multiple organs, yet it confers ICL-induced anti-cancer drug resistance in several cancer subtypes. Here we report three crystal structures of human FAN1 in complex with a 5’ flap DNA substrate, showing that two FAN1 molecules form a head-to-tail dimer to locate the lesion, orient the DNA, and unwind a 5’ flap for subsequent incision. Biochemical experiments further validate our model for FAN1 action, as structure-informed mutations that disrupt protein dimerization, substrate orientation, or flap unwinding impair the structure-specific nuclease activity. Our work elucidates essential aspects of FAN1-DNA lesion recognition and a unique mechanism of incision. These structural insights shed light on the cellular mechanisms underlying organ degeneration protection and cancer drug resistance mediated by FAN1.",2014 Dec 11,"['Zhao, Qi', 'Xue, Xiaoyu', 'Longerich, Simonne', 'Sung, Patrick', 'Xiong, Yong']",Nat Commun,,,True
04fb1656b773a1db9bc2b340aa503fe12132c670,PMC,Structural Insights into 5' Flap DNA Unwinding and Incision by the Human FAN1 Dimer,http://dx.doi.org/10.1038/ncomms6726,PMC4268874,25500724,NO-CC CODE,"Human FANCD2-associated nuclease 1 (FAN1) is a DNA structure-specific nuclease involved in the processing of DNA interstrand crosslinks (ICLs). FAN1 maintains genomic stability and prevents tissue decline in multiple organs, yet it confers ICL-induced anti-cancer drug resistance in several cancer subtypes. Here we report three crystal structures of human FAN1 in complex with a 5’ flap DNA substrate, showing that two FAN1 molecules form a head-to-tail dimer to locate the lesion, orient the DNA, and unwind a 5’ flap for subsequent incision. Biochemical experiments further validate our model for FAN1 action, as structure-informed mutations that disrupt protein dimerization, substrate orientation, or flap unwinding impair the structure-specific nuclease activity. Our work elucidates essential aspects of FAN1-DNA lesion recognition and a unique mechanism of incision. These structural insights shed light on the cellular mechanisms underlying organ degeneration protection and cancer drug resistance mediated by FAN1.",2014 Dec 11,"['Zhao, Qi', 'Xue, Xiaoyu', 'Longerich, Simonne', 'Sung, Patrick', 'Xiong, Yong']",Nat Commun,,,True
8d6b0c0ee9ce6efb0bffee4babfc4b5dba652ff4,PMC,Protocol for Metagenomic Virus Detection in Clinical Specimens,http://dx.doi.org/10.3201/eid2101.140766,PMC4285256,25532973,NO-CC CODE,"Sixty percent of emerging viruses have a zoonotic origin, making transmission from animals a major threat to public health. Prompt identification and analysis of these pathogens are indispensable to taking action toward prevention and protection of the affected population. We quantifiably compared classical and modern approaches of virus purification and enrichment in theory and experiments. Eventually, we established an unbiased protocol for detection of known and novel emerging viruses from organ tissues (tissue-based universal virus detection for viral metagenomics [TUViD-VM]). The final TUViD-VM protocol was extensively validated by using real-time PCR and next-generation sequencing. We could increase the amount of detectable virus nucleic acids and improved the detection of viruses <75,000-fold compared with other tested approaches. This TUViD-VM protocol can be used in metagenomic and virome studies to increase the likelihood of detecting viruses from any biological source.",2015 Jan,"['Kohl, Claudia', 'Brinkmann, Annika', 'Dabrowski, Piotr W.', 'Radonić, Aleksandar', 'Nitsche, Andreas', 'Kurth, Andreas']",Emerg Infect Dis,,,True
0e547f3723a50ef4f55c873f2a65dfbee42cd655,PMC,Protocol for Metagenomic Virus Detection in Clinical Specimens,http://dx.doi.org/10.3201/eid2101.140766,PMC4285256,25532973,NO-CC CODE,"Sixty percent of emerging viruses have a zoonotic origin, making transmission from animals a major threat to public health. Prompt identification and analysis of these pathogens are indispensable to taking action toward prevention and protection of the affected population. We quantifiably compared classical and modern approaches of virus purification and enrichment in theory and experiments. Eventually, we established an unbiased protocol for detection of known and novel emerging viruses from organ tissues (tissue-based universal virus detection for viral metagenomics [TUViD-VM]). The final TUViD-VM protocol was extensively validated by using real-time PCR and next-generation sequencing. We could increase the amount of detectable virus nucleic acids and improved the detection of viruses <75,000-fold compared with other tested approaches. This TUViD-VM protocol can be used in metagenomic and virome studies to increase the likelihood of detecting viruses from any biological source.",2015 Jan,"['Kohl, Claudia', 'Brinkmann, Annika', 'Dabrowski, Piotr W.', 'Radonić, Aleksandar', 'Nitsche, Andreas', 'Kurth, Andreas']",Emerg Infect Dis,,,True
f15bfd75b9e2933456942b0f1867aade1586670f,PMC,Serologic Assessment of Possibility for MERS-CoV Infection in Equids,http://dx.doi.org/10.3201/eid2101.141342,PMC4285277,25531820,NO-CC CODE,,2015 Jan,"['Meyer, Benjamin', 'García-Bocanegra, Ignacio', 'Wernery, Ulrich', 'Wernery, Renate', 'Sieberg, Andrea', 'Müller, Marcel A.', 'Drexler, Jan Felix', 'Drosten, Christian', 'Eckerle, Isabella']",Emerg Infect Dis,,,True
51a2dad6387cc9aa3f9d5d73c83f1df8b4ba021d,PMC,Early-warning health and process indicators for sentinel surveillance in Madagascar 2007-2011,http://dx.doi.org/10.5210/ojphi.v6i3.5400,PMC4292534,25598869,NO-CC CODE,"Background: Epidemics pose major threats in resource-poor countries, and surveillance tools for their early detection and response are often inadequate. In 2007, a sentinel surveillance system was established in Madagascar, with the aim of rapidly identifying potential epidemics of febrile or diarrhoeal syndromes and issuing alerts. We present the health and process indicators for the five years during which this system was constructed, showing the spatiotemporal trends, early-warning sign detection capability and process evaluation through timely analyses of high-quality data. Methods: The Malagasy sentinel surveillance network is currently based on data for fever and diarrhoeal syndromes collected from 34 primary health centres and reported daily via the transmission of short messages from mobile telephones. Data are analysed daily at the Institut Pasteur de Madagascar to make it possible to issue alerts more rapidly, and integrated process indicators (timeliness, data quality) are used to monitor the system. Results: From 2007 to 2011, 917,798 visits were reported. Febrile syndromes accounted for about 11% of visits annually, but the trends observed differed between years and sentinel sites. From 2007 to 2011, 21 epidemic alerts were confirmed. However, delays in data transmission were observed (88% transmitted within 24 hours in 2008; 67% in 2011) and the percentage of forms transmitted each week for validity control decreased from 99.9% in 2007 to 63.5% in 2011. Conclusion: A sentinel surveillance scheme should take into account both epidemiological and process indicators. It must also be governed by the main purpose of the surveillance and by local factors, such as the motivation of healthcare workers and telecommunication infrastructure. Permanent evaluation indicators are required for regular improvement of the system.",2014 Dec 15,"['Rajatonirina, Soatiana', 'Rakotomanana, Fanjasoa', 'Randrianasolo, Laurence', 'Razanajatovo, Norosoa Harline', 'Andriamandimby, Soa Fy', 'Ravolomanana, Lisette', 'Randrianarivo-Solofoniaina, Armand Eugène', 'Reynes, Jean-Marc', 'Piola, Patrice', 'Finlay-Vickers, Alyssa', 'Heraud, Jean-Michel', 'Richard, Vincent']",Online J Public Health Inform,,,True
8db11431c2928d45f9c7587b2fb1a9dabbd2916f,PMC,Detection of Respiratory Viruses in Nasopharyngeal Swab and Adenoid Tissue from Children Submitted to Adenoidectomy: Pre- and Postoperative Analysis,http://dx.doi.org/10.1055/s-0034-1368135,PMC4296995,25992082,NO-CC CODE,"Introduction The presence of respiratory viruses in lymphoid tissues of the nasopharynx and oropharynx and its impact on recurrent infections and hypertrophy of these tissues are not yet fully understood. Objective To identify and determine the prevalence of major respiratory viruses in nasopharyngeal secretions and adenoid tissue pre- and postoperatively of children undergoing adenoidectomy. Methods A prospective observational study was conducted in 36 patients under 12 years of age with upper airway lymphoid hypertrophy who were undergoing adenoidectomy, in which various respiratory viruses were investigated using real-time polymerase chain reaction in adenoid tissue and nasopharyngeal secretions collected preoperatively and 30 days postoperatively. Results At least 1 viral agent was isolated in any of the samples collected in 58.3% of children and 25.9% of total samples. Respiratory viruses were identified in 33.8% of preoperative nasopharyngeal specimens and in 19.8% of postoperative secretion. Of the 21 patients with positive results for any respiratory virus, 6 (28.6%) had more than 1 virus. Considering all 36 respiratory viruses found, the main agent isolated was rhinovirus (27.8%), followed by bocavirus (22.2%). Conclusion The virus found more frequently in all samples was rhinovirus. After removal of adenoid tissue, there was a decrease in the prevalence of the virus contained in nasopharyngeal secretion 30 days after surgery.",2014 Apr 17,"['Biill Primo, Osvaldo Vinícius', 'Lourenço, Edmir Américo', 'Passos, Saulo Duarte']",Int Arch Otorhinolaryngol,,,True
1c5f9e0dfbba108b9d431f99fe2274ad0c47e7bc,PMC,Sequencing of the human IG light chain loci from a hydatidiform mole BAC library reveals locus-specific signatures of genetic diversity,http://dx.doi.org/10.1038/gene.2014.56,PMC4304971,25338678,NO-CC CODE,"Germline variation at immunoglobulin (IG) loci is critical for pathogen-mediated immunity, but establishing complete haplotype sequences in these regions has been problematic because of complex sequence architecture and diploid source DNA. We sequenced BAC clones from the effectively haploid human hydatidiform mole cell line, CHM1htert, across the light chain IG loci, kappa (IGK) and lambda (IGL), creating single haplotype representations of these regions. The IGL haplotype generated here is 1.25 Mb of contiguous sequence, including four novel V alleles and one novel C allele and an 11.9 kb insertion. The CH17 IGK haplotype consists of two 644 kb proximal and 466 kb distal contigs separated by a large gap of unknown size; these assemblies added 49 kb of unique sequence extending into this gap. Our analysis also resulted in the characterization of seven novel IGKV alleles and a 16.7 kb region exhibiting signatures of interlocus sequence exchange between distal and proximal IGKV gene clusters. Genetic diversity in IGK/IGL was compared to that of the IG heavy chain (IGH) locus within the same haploid genome, revealing 3-fold (IGK) and 6-fold (IGL) higher diversity in the IGH locus, potentially associated with increased levels of segmental duplication and the telomeric location of IGH.",2015 Oct 23 Jan-Feb,"['Watson, Corey T.', 'Steinberg, Karyn Meltz', 'Graves, Tina A.', 'Warren, Rene L.', 'Malig, Maika', 'Schein, Jacqueline', 'Wilson, Richard K.', 'Holt, Robert A.', 'Eichler, Evan E.', 'Breden, Felix']",Genes Immun,,,True
128fc4c67ef01890625e271452e1b9c7a4ac7984,PMC,Therapeutic vaccination and immunomodulation in the treatment of chronic hepatitis B: preclinical studies in the woodchuck,http://dx.doi.org/10.1007/s00430-014-0379-5,PMC4305085,25535101,NO-CC CODE,"Infection with hepatitis B virus (HBV) may lead to subclinical, acute or chronic hepatitis. In the prevaccination era, HBV infections were endemic due to frequent mother to child transmission in large regions of the world. However, there are still estimated 240 million chronic HBV carriers today and ca. 620,000 patients die per year due to HBV-related liver diseases. Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to satisfactory results. Induction of HBV-specific T cells by therapeutic vaccination or immunomodulation may be an innovative strategy to overcome virus persistence. Vaccination with commercially available HBV vaccines in patients with or without therapeutic reduction of viral load did not result in effective immune control of HBV infection, suggesting that combination of antiviral treatment with new formulations of therapeutic vaccines is needed. The woodchuck (Marmota monax) and its HBV-like woodchuck hepatitis virus are a useful preclinical animal model for developing new therapeutic approaches in chronic hepadnaviral infections. Several innovative approaches combining antiviral treatments using nucleos(t)ide analogues, with prime-boost vaccination using DNA vaccines, new hepadnaviral antigens or recombinant adenoviral vectors were tested in the woodchuck model. In this review, we summarize these encouraging results obtained with these therapeutic vaccines. In addition, we present potential innovations in immunostimulatory strategies by blocking the interaction of the inhibitory programmed death receptor 1 with its ligand in this animal model.",2015 Dec 23,"['Kosinska, Anna D.', 'Liu, Jia', 'Lu, Mengji', 'Roggendorf, Michael']",Med Microbiol Immunol,,,True
758e9c4e4ff49b4e2a9a3a14014edfc567e521fa,PMC,Evaluation of Border Entry Screening for Infectious Diseases in Humans,http://dx.doi.org/10.3201/eid2102.131610,PMC4313627,25625224,NO-CC CODE,"In response to the severe acute respiratory syndrome (SARS) pandemic of 2003 and the influenza pandemic of 2009, many countries instituted border measures as a means of stopping or slowing the spread of disease. The measures, usually consisting of a combination of border entry/exit screening, quarantine, isolation, and communications, were resource intensive, and modeling and observational studies indicate that border screening is not effective at detecting infectious persons. Moreover, border screening has high opportunity costs, financially and in terms of the use of scarce public health staff resources during a time of high need. We discuss the border-screening experiences with SARS and influenza and propose an approach to decision-making for future pandemics. We conclude that outbreak-associated communications for travelers at border entry points, together with effective communication with clinicians and more effective disease control measures in the community, may be a more effective approach to the international control of communicable diseases.",2015 Feb,"['Selvey, Linda A.', 'Antão, Catarina', 'Hall, Robert']",Emerg Infect Dis,,,True
7ee6196d0be6f703dd2e2a96b94cbe899f7400d2,PMC,"Cluster of Middle East Respiratory Syndrome Coronavirus Infections in Iran, 2014",http://dx.doi.org/10.3201/eid2102.141405,PMC4313658,25626079,NO-CC CODE,"During January 2013–August 2014, a total of 1,800 patients in Iran who had respiratory illness were tested for Middle East respiratory syndrome coronavirus. A cluster of 5 cases occurred in Kerman Province during May–July 2014, but virus transmission routes for some infections were unclear.",2015 Feb,"['Yavarian, Jila', 'Rezaei, Farshid', 'Shadab, Azadeh', 'Soroush, Mahmood', 'Gooya, Mohammad Mehdi', 'Azad, Talat Mokhtari']",Emerg Infect Dis,,,True
57e6620ed5a7142981da23d408a094c2e01bed35,PMC,"Influenza D Virus in Cattle, France, 2011–2014",http://dx.doi.org/10.3201/eid2102.141449,PMC4313661,25628038,NO-CC CODE,"A new influenza virus, genus D, isolated in US pigs and cattle, has also been circulating in cattle in France. It was first identified there in 2011, and an increase was detected in 2014. The virus genome in France is 94%–99% identical to its US counterpart, which suggests intercontinental spillover.",2015 Feb,"['Ducatez, Mariette F.', 'Pelletier, Claire', 'Meyer, Gilles']",Emerg Infect Dis,,,True
eef0cab385662b98975be9e90899f63f19243bce,PMC,"Year in review in Intensive Care Medicine 2014: I. Cardiac dysfunction and cardiac arrest, ultrasound, neurocritical care, ICU-acquired weakness, nutrition, acute kidney injury, and miscellaneous",http://dx.doi.org/10.1007/s00134-015-3665-9,PMC4315874,,NO-CC CODE,,2015 Jan 30,"['Citerio, Giuseppe', 'Bakker, Jan', 'Bassetti, Matteo', 'Benoit, Dominique', 'Cecconi, Maurizio', 'Curtis, J. Randall', 'Doig, Gordon S.', 'Herridge, Margaret', 'Jaber, Samir', 'Joannidis, Michael', 'Papazian, Laurent', 'Perner, Anders', 'Peters, Mark J.', 'Singer, Pierre', 'Smith, Martin', 'Soares, Marcio', 'Torres, Antoni', 'Vieillard-Baron, Antoine', 'Timsit, Jean-François', 'Azoulay, Elie']",Intensive Care Med,,,True
2e6b763befef8fc1df4868231c49171d57793e8a,PMC,"Resistance Prediction in AML: Analysis of 4,601 Patients from MRC/NCRI, HOVON/SAKK, SWOG, and MD Anderson Cancer Center",http://dx.doi.org/10.1038/leu.2014.242,PMC4318722,25113226,NO-CC CODE,"Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver operator characteristic curves (AUC) to quantify our ability to predict therapeutic resistance in individual patients where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4,601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in MRC/NCRI, HOVON, SWOG, and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk, and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death (“primary refractoriness”). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival (RFS), was even more difficult. Our ability to forecast resistance based on routinely available pre-treatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and post-treatment data to optimize resistance prediction in AML.",2015 Feb 12,"['Walter, Roland B.', 'Othus, Megan', 'Burnett, Alan K.', 'Löwenberg, Bob', 'Kantarjian, Hagop M.', 'Ossenkoppele, Gert J.', 'Hills, Robert K.', 'Ravandi, Farhad', 'Pabst, Thomas', 'Evans, Anna', 'Pierce, Sherry R.', 'Vekemans, Marie-Christiane', 'Appelbaum, Frederick R.', 'Estey, Elihu H.']",Leukemia,,,True
6203b7c7808aac525f83c3cc7d0107cf90344259,PMC,Respiratory Syncytial Virus Outbreak in the Basic Military Training Camp of the Republic of Korea Air Force,http://dx.doi.org/10.3961/jpmph.14.037,PMC4322513,25652706,NO-CC CODE,"OBJECTIVES: An outbreak of acute febrile illness occurred in the Republic of Korea Air Force boot camp from May to July 2011. An epidemiological investigation of the causative agent, which was of a highly infective nature, was conducted. METHODS: Throat swabs were carried out and a multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) assay was performed to identify possible causative factors. RESULTS: The mean age of patients who had febrile illness during the study period was 20.24 years. The multiplex RT-PCR assay identified respiratory syncytial virus (RSV) as the causative agent. The main symptoms were sore throat (76.0%), sputum (72.8%), cough (72.1%), tonsillar hypertrophy (67.9%), and rhinorrhea (55.9%). The mean temperature was 38.75°C and the attack rate among the recruits was 15.7% (588 out of 3750 recruits), while the mean duration of fever was 2.3 days. The prognosis was generally favorable with supportive care but recurrent fever occurred in 10.1% of the patients within a month. CONCLUSIONS: This is the first epidemiological study of an RSV outbreak that developed in a healthy young adult group. In the event of an outbreak of an acute febrile illness of a highly infective nature in facilities used by a young adult group, RSV should be considered among the possible causative agents.",2015 Jan 14,"['Park, Won-Ju', 'Yoo, Seok-Ju', 'Lee, Suk-Ho', 'Chung, Jae-Woo', 'Jang, Keun-Ho', 'Moon, Jai-Dong']",J Prev Med Public Health,,,True
b2b148720d1cf79fbeac9a409962bf9e2e190c4a,PMC,Visualization of HTLV-1–Specific Cytotoxic T Lymphocytes in the Spinal Cords of Patients With HTLV-1–Associated Myelopathy/Tropical Spastic Paraparesis,http://dx.doi.org/10.1097/NEN.0000000000000141,PMC4336315,25470342,NO-CC CODE,"Activated human T-lymphotropic virus type-1 (HTLV-1)–specific CD8-positive cytotoxic T lymphocytes (CTLs) are markedly increased in the periphery of patients with HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP), an HTLV-1–induced inflammatory disease of the CNS. Although virus-specific CTLs play a pivotal role to eliminate virus-infected cells, the potential role of HTLV-1–specific CTLs in the pathogenesis of HAM/TSP remains unclear. To address this issue, we evaluated the infiltration of HTLV-1–specific CTLs and the expression of HTLV-1 proteins in the spinal cords of 3 patients with HAM/TSP. Confocal laser scanning microscopy with our unique staining procedure made it possible to visualize HTLV-1–specific CTLs infiltrating the CNS of the HAM/TSP patients. The frequency of HTLV-1–specific CTLs was more than 20% of CD8-positive cells infiltrating the CNS. In addition, HTLV-1 proteins were detected in CD4-positive infiltrating T lymphocytes but not CNS resident cells. Although neurons were generally preserved, apoptotic oligodendrocytes were frequently in contact with CD8-positive cells; this likely resulted in demyelination. These findings suggest that the immune responses of the CTLs against HTLV-1–infected CD4-positive lymphocytes migrating into the CNS resulted in bystander neural damage.",2015 Jan 18,"['Matsuura, Eiji', 'Kubota, Ryuji', 'Tanaka, Yuetsu', 'Takashima, Hiroshi', 'Izumo, Shuji']",J Neuropathol Exp Neurol,,,True
5f2ad6d0fea48889b06eafdc3be79078b9e80504,PMC,"Comparison of Porcine Epidemic Diarrhea Viruses from Germany and the United States, 2014",http://dx.doi.org/10.3201/eid2103.141165,PMC4344272,25695311,NO-CC CODE,"Since 2013, highly virulent porcine epidemic diarrhea virus has caused considerable economic losses in the United States. To determine the relation of US strains to those recently causing disease in Germany, we compared genomes and found that the strain from Germany is closely related to variants in the United States.",2015 Mar,"['Hanke, Dennis', 'Jenckel, Maria', 'Petrov, Anja', 'Ritzmann, Mathias', 'Stadler, Julia', 'Akimkin, Valerij', 'Blome, Sandra', 'Pohlmann, Anne', 'Schirrmeier, Horst', 'Beer, Martin', 'Höper, Dirk']",Emerg Infect Dis,,,True
175f06ec35e11179a9b566479706ce4222768b23,PMC,"Comparison of Porcine Epidemic Diarrhea Viruses from Germany and the United States, 2014",http://dx.doi.org/10.3201/eid2103.141165,PMC4344272,25695311,NO-CC CODE,"Since 2013, highly virulent porcine epidemic diarrhea virus has caused considerable economic losses in the United States. To determine the relation of US strains to those recently causing disease in Germany, we compared genomes and found that the strain from Germany is closely related to variants in the United States.",2015 Mar,"['Hanke, Dennis', 'Jenckel, Maria', 'Petrov, Anja', 'Ritzmann, Mathias', 'Stadler, Julia', 'Akimkin, Valerij', 'Blome, Sandra', 'Pohlmann, Anne', 'Schirrmeier, Horst', 'Beer, Martin', 'Höper, Dirk']",Emerg Infect Dis,,,False
47b2413d069283b3278cd69e2777f53758af19b1,PMC,Porcine Epidemic Diarrhea Virus Replication in Duck Intestinal Cell Line,http://dx.doi.org/10.3201/eid2103.141658,PMC4344288,25695828,NO-CC CODE,,2015 Mar,"Khatri, Mahesh",Emerg Infect Dis,,,True
c5afb030f736eb07f8b16ea8bb39dd5c7007c0b2,PMC,Porcine Epidemic Diarrhea Virus Replication in Duck Intestinal Cell Line,http://dx.doi.org/10.3201/eid2103.141658,PMC4344288,25695828,NO-CC CODE,,2015 Mar,"Khatri, Mahesh",Emerg Infect Dis,,,False
52ce19fe79de46d9bb0fa7e75a0631fed2d3efd2,PMC,Bioinformatics analysis of SARS coronavirus genome polymorphism,http://dx.doi.org/10.1186/1471-2105-5-65,PMC434493,15161495,NO-CC CODE,"BACKGROUND: We have compared 38 isolates of the SARS-CoV complete genome. The main goal was twofold: first, to analyze and compare nucleotide sequences and to identify positions of single nucleotide polymorphism (SNP), insertions and deletions, and second, to group them according to sequence similarity, eventually pointing to phylogeny of SARS-CoV isolates. The comparison is based on genome polymorphism such as insertions or deletions and the number and positions of SNPs. RESULTS: The nucleotide structure of all 38 isolates is presented. Based on insertions and deletions and dissimilarity due to SNPs, the dataset of all the isolates has been qualitatively classified into three groups each having their own subgroups. These are the A-group with ""regular"" isolates (no insertions / deletions except for 5' and 3' ends), the B-group of isolates with ""long insertions"", and the C-group of isolates with ""many individual"" insertions and deletions. The isolate with the smallest average number of SNPs, compared to other isolates, has been identified (TWH). The density distribution of SNPs, insertions and deletions for each group or subgroup, as well as cumulatively for all the isolates is also presented, along with the gene map for TWH. Since individual SNPs may have occurred at random, positions corresponding to multiple SNPs (occurring in two or more isolates) are identified and presented. This result revises some previous results of a similar type. Amino acid changes caused by multiple SNPs are also identified (for the annotated sequences, as well as presupposed amino acid changes for non-annotated ones). Exact SNP positions for the isolates in each group or subgroup are presented. Finally, a phylogenetic tree for the SARS-CoV isolates has been produced using the CLUSTALW program, showing high compatibility with former qualitative classification. CONCLUSIONS: The comparative study of SARS-CoV isolates provides essential information for genome polymorphism, indication of strain differences and variants evolution. It may help with the development of effective treatment.",2004 May 25,"['Pavlović-Lažetić, Gordana M', 'Mitić, Nenad S', 'Beljanski, Miloš V']",BMC Bioinformatics,,,True
bbe2e49fac5f007f3313b35f9b264bb4219aa67d,PMC,The Role of Carbohydrates in Infection Strategies of Enteric Pathogens,http://dx.doi.org/10.2149/tmh.2014-25,PMC4361345,25859152,NO-CC CODE,"Enteric pathogens cause considerable public health concerns worldwide including tropical regions. Here, we review the roles of carbohydrates in the infection strategies of various enteric pathogens including viruses, bacteria and protozoa, which infect the epithelial lining of the human and animal intestine. At host cell entry, enteric viruses, including norovirus, recognize mainly histo-blood group antigens. At the initial step of bacterial infections, carbohydrates also function as receptors for attachment. Here, we describe the function of carbohydrates in infection by Salmonella enterica and several bacterial species that produce a variety of fimbrial adhesions. During invasion by enteropathogenic protozoa, apicomplexan parasites utilize sialic acids or sulfated glycans. Carbohydrates serve as receptors for infection by these microbes; however, their usage of carbohydrates varies depending on the microbe. On the surface of the mucosal tissues of the gastrointestinal tract, various carbohydrate moieties are present and play a crucial role in infection, representing the site of infection or route of access for most microbes. During the infection and/or invasion process of the microbes, carbohydrates function as receptors for various microbes, but they can also function as a barrier to infection. One approach to develop effective prophylactic and therapeutic antimicrobial agents is to modify the drug structure. Another approach is to modify the mode of inhibition of infection depending on the individual pathogen by using and mimicking the interactions with carbohydrates. In addition, similarities in mode of infection may also be utilized. Our findings will be useful in the development of new drugs for the treatment of enteric pathogens.",2015 Mar 15,"['Kato, Kentaro', 'Ishiwa, Akiko']",Trop Med Health,,,True
2bfa631d66f7e59bd7de5316ecc45b9f44352f1b,PMC,Merging Economics and Epidemiology to Improve the Prediction and Management of Infectious Disease,http://dx.doi.org/10.1007/s10393-014-0963-6,PMC4366543,25233829,NO-CC CODE,"Mathematical epidemiology, one of the oldest and richest areas in mathematical biology, has significantly enhanced our understanding of how pathogens emerge, evolve, and spread. Classical epidemiological models, the standard for predicting and managing the spread of infectious disease, assume that contacts between susceptible and infectious individuals depend on their relative frequency in the population. The behavioral factors that underpin contact rates are not generally addressed. There is, however, an emerging a class of models that addresses the feedbacks between infectious disease dynamics and the behavioral decisions driving host contact. Referred to as “economic epidemiology” or “epidemiological economics,” the approach explores the determinants of decisions about the number and type of contacts made by individuals, using insights and methods from economics. We show how the approach has the potential both to improve predictions of the course of infectious disease, and to support development of novel approaches to infectious disease management.",2014 Sep 19,"['Perrings, Charles', 'Castillo-Chavez, Carlos', 'Chowell, Gerardo', 'Daszak, Peter', 'Fenichel, Eli P.', 'Finnoff, David', 'Horan, Richard D.', 'Kilpatrick, A. Marm', 'Kinzig, Ann P.', 'Kuminoff, Nicolai V.', 'Levin, Simon', 'Morin, Benjamin', 'Smith, Katherine F.', 'Springborn, Michael']",Ecohealth,,,True
10f76405b60d19a29ab68f2b476a870d91d5ea7d,PMC,"Influenza A and B Viruses but Not MERS-CoV in Hajj Pilgrims, Austria, 2014",http://dx.doi.org/10.3201/eid2104.141745,PMC4378469,25811672,NO-CC CODE,,2015 Apr,"['Aberle, Judith H.', 'Popow-Kraupp, Theresia', 'Kreidl, Peter', 'Laferl, Hermann', 'Heinz, Franz X.', 'Aberle, Stephan W.']",Emerg Infect Dis,,,True
5adf6613fe8688c9c324efb8cc68844c3535c81f,PMC,Bat Coronavirus in Brazil Related to Appalachian Ridge and Porcine Epidemic Diarrhea Viruses,http://dx.doi.org/10.3201/eid2104.141783,PMC4378475,25811911,NO-CC CODE,,2015 Apr,"['Simas, Paulo Vitor Marques', 'Barnabé, Ana Caroline de Souza', 'Durães-Carvalho, Ricardo', 'Neto, Daniel Ferreira de Lima', 'Caserta, Leonardo Cardia', 'Artacho, Luiza', 'Jacomassa, Fábio André Facco', 'Martini, Matheus Cavalheiro', 'Bianchi dos Santos, Márcia Mercês Aparecida', 'Felippe, Paulo Anselmo Nunes', 'Ferreira, Helena Lage', 'Arns, Clarice Weis']",Emerg Infect Dis,,,True
31ce106a9007d3c92b32625c945aada3eb49a5a2,PMC,Bat Coronavirus in Brazil Related to Appalachian Ridge and Porcine Epidemic Diarrhea Viruses,http://dx.doi.org/10.3201/eid2104.141783,PMC4378475,25811911,NO-CC CODE,,2015 Apr,"['Simas, Paulo Vitor Marques', 'Barnabé, Ana Caroline de Souza', 'Durães-Carvalho, Ricardo', 'Neto, Daniel Ferreira de Lima', 'Caserta, Leonardo Cardia', 'Artacho, Luiza', 'Jacomassa, Fábio André Facco', 'Martini, Matheus Cavalheiro', 'Bianchi dos Santos, Márcia Mercês Aparecida', 'Felippe, Paulo Anselmo Nunes', 'Ferreira, Helena Lage', 'Arns, Clarice Weis']",Emerg Infect Dis,,,False
da445fcbe5ce291f6749c02784523b331c64baf1,PMC,"Candidate New Rotavirus Species in Sheltered Dogs, Hungary",http://dx.doi.org/10.3201/eid2104.141370,PMC4378476,25811414,NO-CC CODE,"We identified unusual rotavirus strains in fecal specimens from sheltered dogs in Hungary by viral metagenomics. The novel rotavirus species displayed limited genome sequence homology to representatives of the 8 rotavirus species, A–H, and qualifies as a candidate new rotavirus species that we tentatively named Rotavirus I.",2015 Apr,"['Mihalov-Kovács, Eszter', 'Gellért, Ákos', 'Marton, Szilvia', 'Farkas, Szilvia L.', 'Fehér, Enikő', 'Oldal, Miklós', 'Jakab, Ferenc', 'Martella, Vito', 'Bányai, Krisztián']",Emerg Infect Dis,,,True
e7225a44e3ba71ff67dae1b7dcdaba98dbe4e22b,PMC,"Candidate New Rotavirus Species in Sheltered Dogs, Hungary",http://dx.doi.org/10.3201/eid2104.141370,PMC4378476,25811414,NO-CC CODE,"We identified unusual rotavirus strains in fecal specimens from sheltered dogs in Hungary by viral metagenomics. The novel rotavirus species displayed limited genome sequence homology to representatives of the 8 rotavirus species, A–H, and qualifies as a candidate new rotavirus species that we tentatively named Rotavirus I.",2015 Apr,"['Mihalov-Kovács, Eszter', 'Gellért, Ákos', 'Marton, Szilvia', 'Farkas, Szilvia L.', 'Fehér, Enikő', 'Oldal, Miklós', 'Jakab, Ferenc', 'Martella, Vito', 'Bányai, Krisztián']",Emerg Infect Dis,,,True
ec38b733b394029c900b0bf2b3ee8c186b7e9956,PMC,Lack of Middle East Respiratory Syndrome Coronavirus Transmission from Infected Camels,http://dx.doi.org/10.3201/eid2104.141949,PMC4378477,25811546,NO-CC CODE,"To determine risk for Middle East respiratory syndrome coronavirus transmission from camels to humans, we tested serum from 191 persons with various levels of exposure to an infected dromedary herd. We found no serologic evidence of human infection, suggesting that zoonotic transmission of this virus from dromedaries is rare.",2015 Apr,"['Hemida, Maged G.', 'Al-Naeem, Abdulmohsen', 'Perera, Ranawaka A.P.M.', 'Chin, Alex W.H.', 'Poon, Leo L.M.', 'Peiris, Malik']",Emerg Infect Dis,,,True
35b6dc25346a6ccc941728e55628decf40327a0c,PMC,Pathogenicity of 2 Porcine Deltacoronavirus Strains in Gnotobiotic Pigs,http://dx.doi.org/10.3201/eid2104.141859,PMC4378491,25811229,NO-CC CODE,"To verify whether porcine deltacoronavirus infection induces disease, we inoculated gnotobiotic pigs with 2 virus strains (OH-FD22 and OH-FD100) identified by 2 specific reverse transcription PCRs. At 21–120 h postinoculation, pigs exhibited severe diarrhea, vomiting, fecal shedding of virus, and severe atrophic enteritis. These findings confirm that these 2 strains are enteropathogenic in pigs.",2015 Apr,"['Jung, Kwonil', 'Hu, Hui', 'Eyerly, Bryan', 'Lu, Zhongyan', 'Chepngeno, Juliet', 'Saif, Linda J.']",Emerg Infect Dis,,,True
b44258fb9be12d1ddecb77617f2cf7914313d35c,PMC,NCBI Viral Genomes Resource,http://dx.doi.org/10.1093/nar/gku1207,PMC4383986,25428358,NO-CC CODE,"Recent technological innovations have ignited an explosion in virus genome sequencing that promises to fundamentally alter our understanding of viral biology and profoundly impact public health policy. Yet, any potential benefits from the billowing cloud of next generation sequence data hinge upon well implemented reference resources that facilitate the identification of sequences, aid in the assembly of sequence reads and provide reference annotation sources. The NCBI Viral Genomes Resource is a reference resource designed to bring order to this sequence shockwave and improve usability of viral sequence data. The resource can be accessed at http://www.ncbi.nlm.nih.gov/genome/viruses/ and catalogs all publicly available virus genome sequences and curates reference genome sequences. As the number of genome sequences has grown, so too have the difficulties in annotating and maintaining reference sequences. The rapid expansion of the viral sequence universe has forced a recalibration of the data model to better provide extant sequence representation and enhanced reference sequence products to serve the needs of the various viral communities. This, in turn, has placed increased emphasis on leveraging the knowledge of individual scientific communities to identify important viral sequences and develop well annotated reference virus genome sets.",2015 Jan 28,"['Brister, J. Rodney', 'Ako-adjei, Danso', 'Bao, Yiming', 'Blinkova, Olga']",Nucleic Acids Res,,,True
9cb04b84b292eff39712e9af5a9f4db2c61a6dcd,PMC,Celiac and non-celiac gluten sensitivity: a review on the association with schizophrenia and mood disorders,http://dx.doi.org/10.1007/s13317-014-0064-0,PMC4389040,26000156,NO-CC CODE,"An association between many psychiatric and gluten-related disorders has been known for some time. In the case of schizophrenia and mood disorders, the major psychiatric disorders, there is much evidence, not without contradictions, of a possible association between schizophrenia and celiac disease. The association between mood disorders and gluten-related disorders, especially celiac disease, has only been studied for depression, often coupled with anxiety, and very recently for bipolar disorder. Since non-celiac gluten sensitivity is now known to be different from celiac disease, many studies have shown that gluten sensitivity is also associated with major psychiatric disorders. Here we review the literature on the association between schizophrenia/mood disorders and celiac disease/gluten sensitivity, pointing out the differences between these associations.",2014 Oct 16,"['Porcelli, Brunetta', 'Verdino, Valeria', 'Bossini, Letizia', 'Terzuoli, Lucia', 'Fagiolini, Andrea']",Auto Immun Highlights,,,True
48f7616ac0756fa4bcdb79fef569643b929b108e,PMC,In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1,http://dx.doi.org/10.7555/JBR.29.20130024,PMC4389116,25859271,NO-CC CODE,"This research focused on the modification of the functional groups of oseltamivir as neuraminidase inhibitor against influenza A virus subtype H1N1. Interactions of three of the best ligands were evaluated in the hydrated state using molecular dynamics simulation at two different temperatures. The docking result showed that AD3BF2D ligand (N-[(1S,6R)-5-amino-5-{[(2R,3S,4S)-3,4-dihydroxy-4-(hydroxymethyl) tetrahydrofuran-2-yl]oxy}-4-formylcyclohex-3-en-1-yl]acetamide-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate) had better binding energy values than standard oseltamivir. AD3BF2D had several interactions, including hydrogen bonds, with the residues in the catalytic site of neuraminidase as identified by molecular dynamics simulation. The results showed that AD3BF2D ligand can be used as a good candidate for neuraminidase inhibitor to cope with influenza A virus subtype H1N1.",2015 Apr 12,"['Tambunan, Usman Sumo Friend', 'Rachmania, Rizky Archintya', 'Parikesit, Arli Aditya']",J Biomed Res,,,True
791bb7fd75fdeed7781334dfb35f216bcea492df,PMC,Organic Carbamates in Drug Design and Medicinal Chemistry,http://dx.doi.org/10.1021/jm501371s,PMC4393377,25565044,NO-CC CODE,"[Image: see text] The carbamate group is a key structural motif in many approved drugs and prodrugs. There is an increasing use of carbamates in medicinal chemistry and many derivatives are specifically designed to make drug–target interactions through their carbamate moiety. In this Perspective, we present properties and stabilities of carbamates, reagents and chemical methodologies for the synthesis of carbamates, and recent applications of carbamates in drug design and medicinal chemistry.",2015 Apr 9,"['Ghosh, Arun K.', 'Brindisi, Margherita']",J Med Chem,,,True
623c7837507886a9e4cc4e4e58a95aa81cb5406a,PMC,Epidemiology and Virology of Acute Respiratory Infections During the First Year of Life: A Birth Cohort Study in Vietnam,http://dx.doi.org/10.1097/INF.0000000000000643,PMC4418783,25674708,NO-CC CODE,"BACKGROUND: Understanding viral etiology and age-specific incidence of acute respiratory infections in infants can help identify risk groups and inform vaccine delivery, but community-based data is lacking from tropical settings. METHODS: One thousand four hundred and seventy-eight infants in urban Ho Chi Minh City and 981 infants in a semi-rural district in southern Vietnam were enrolled at birth and followed to 1 year of age. Acute respiratory infection (ARI) episodes were identified through clinic-based illness surveillance, hospital admissions and self-reports. Nasopharyngeal swabs were collected from infants with respiratory symptoms and tested for 14 respiratory pathogens using multiplex reverse transcription-polymerase chain reaction. RESULTS: Estimated incidence of ARI was 542 and 2691 per 1000 infant-years, and hospitalization rates for ARI were 81 and 138 per 1000 infant-years, in urban and semi-rural cohorts, respectively, from clinic- and hospital-based surveillance. However self-reported ARI episodes were just 1.5-fold higher in the semi-rural versus urban cohort, indicating that part of the urban–rural difference was explained by under-ascertainment in the urban cohort. Incidence was higher in infants ≥6 months of age than <6 months, but this was pathogen-specific. One or more viruses were detected in 53% (urban) and 64% (semi-rural) of samples from outpatients with ARI and in 78% and 66% of samples from hospitalized ARI patients, respectively. The most frequently detected viruses were rhinovirus, respiratory syncytial virus, influenza virus A and bocavirus. ARI-associated hospitalizations were associated with longer stays and more frequent ICU admission than other infections. CONCLUSIONS: ARI is a significant cause of morbidity in Vietnamese infants and influenza virus A is an under-appreciated cause of vaccine-preventable disease and hospitalizations in this tropical setting. Public health strategies to reduce infant ARI incidence and hospitalization rates are needed.",2015 Apr 24,"['Anders, Katherine L.', 'Nguyen, Hoa L.', 'Nguyen, Nguyet Minh', 'Van Thuy, Nguyen Thi', 'Hong Van, Nguyen Thi', 'Hieu, Nguyen Trong', 'Hong Tham, Nguyen Thi', 'Thanh Ha, Phan Thi', 'Lien, Le Bich', 'Vinh Chau, Nguyen Van', 'Ty Hang, Vu Thi', 'van Doorn, H. Rogier', 'Simmons, Cameron P.']",Pediatr Infect Dis J,,,True
b499a41ad1d85a0e071b59e60065c874e534911d,PMC,Coronavirus 3CL(pro )proteinase cleavage sites: Possible relevance to SARS virus pathology,http://dx.doi.org/10.1186/1471-2105-5-72,PMC442122,15180906,NO-CC CODE,"BACKGROUND: Despite the passing of more than a year since the first outbreak of Severe Acute Respiratory Syndrome (SARS), efficient counter-measures are still few and many believe that reappearance of SARS, or a similar disease caused by a coronavirus, is not unlikely. For other virus families like the picornaviruses it is known that pathology is related to proteolytic cleavage of host proteins by viral proteinases. Furthermore, several studies indicate that virus proliferation can be arrested using specific proteinase inhibitors supporting the belief that proteinases are indeed important during infection. Prompted by this, we set out to analyse and predict cleavage by the coronavirus main proteinase using computational methods. RESULTS: We retrieved sequence data on seven fully sequenced coronaviruses and identified the main 3CL proteinase cleavage sites in polyproteins using alignments. A neural network was trained to recognise the cleavage sites in the genomes obtaining a sensitivity of 87.0% and a specificity of 99.0%. Several proteins known to be cleaved by other viruses were submitted to prediction as well as proteins suspected relevant in coronavirus pathology. Cleavage sites were predicted in proteins such as the cystic fibrosis transmembrane conductance regulator (CFTR), transcription factors CREB-RP and OCT-1, and components of the ubiquitin pathway. CONCLUSIONS: Our prediction method NetCorona predicts coronavirus cleavage sites with high specificity and several potential cleavage candidates were identified which might be important to elucidate coronavirus pathology. Furthermore, the method might assist in design of proteinase inhibitors for treatment of SARS and possible future diseases caused by coronaviruses. It is made available for public use at our website: .",2004 Jun 6,"['Kiemer, Lars', 'Lund, Ole', 'Brunak, Søren', 'Blom, Nikolaj']",BMC Bioinformatics,,,True
8004486cd94fe30d59168de8109ebfe241223a13,PMC,Chemical and Structural Aspects of Ebola Virus Entry Inhibitors,http://dx.doi.org/10.1021/id500025n,PMC4426353,25984565,NO-CC CODE,"[Image: see text] The Ebolaviruses are members of the family Filoviridae (“filoviruses”) and cause severe hemhorragic fever with human case fatality rates as high as 90%. Infection requires attachment of the viral particle to cells and triggering of membrane fusion between the host and viral membranes, a process that occurs in the host endosome and is facilitated by the envelope glycoprotein (GP). One potential strategy for therapeutic intervention is the development of agents (antibodies, peptides, and small molecules) that can interfere with viral entry aspects such as attachment, uptake, priming, or membrane fusion. This paper highlights recent developments in the discovery and evaluation of therapeutic entry inhibitors and identifies opportunities moving forward.",2015 Jan 9,"['Nyakatura, Elisabeth K.', 'Frei, Julia C.', 'Lai, Jonathan R.']",ACS Infect Dis,,,True
f9c05a5c33ef91bbf61d086c882b60a5e6510b21,PMC,The Axl receptor tyrosine kinase is a discriminator of macrophage function in the inflamed lung,http://dx.doi.org/10.1038/mi.2014.129,PMC4430298,25603826,NO-CC CODE,"Much of the biology surrounding macrophage functional specificity has arisen through examining inflammation-induced polarising signals, but this also occurs in homeostasis, requiring tissue-specific environmental triggers that influence macrophage phenotype and function. The TAM receptor family of receptor tyrosine kinases (Tyro3, Axl and MerTK) mediates the non-inflammatory removal of apoptotic cells by phagocytes through the bridging phosphatidylserine-binding molecules Gas6 or Protein S. We show that one such TAM receptor (Axl) is exclusively expressed on mouse airway macrophages, but not interstitial macrophages and other lung leukocytes, under homeostatic conditions and is constitutively ligated to Gas6. Axl expression is potently induced by GM-CSF expressed in the healthy and inflamed airway, and by type I interferon or TLR3 stimulation on human and mouse macrophages, indicating potential involvement of Axl in apoptotic cell removal under inflammatory conditions. Indeed, an absence of Axl does not cause sterile inflammation in health, but leads to exaggerated lung inflammatory disease upon influenza infection. These data imply that Axl allows specific identification of airway macrophages, and that its expression is critical for macrophage functional compartmentalisation in the airspaces or lung interstitium. We propose that this may be a critical feature to prevent excessive inflammation due to secondary necrosis of apoptotic cells that have not been cleared by efferocytosis.",2015 Sep 21,"['Fujimori, Toshifumi', 'Grabiec, Aleksander M', 'Kaur, Manminder', 'Bell, Thomas J', 'Fujino, Naoya', 'Cook, Peter C', 'Svedberg, Freya R', 'MacDonald, Andrew S', 'Maciewicz, Rose A', 'Singh, Dave', 'Hussell, Tracy']",Mucosal Immunol,,,True
a5043203032681fb5c6e5397873611200a3378a8,PMC,The Axl receptor tyrosine kinase is a discriminator of macrophage function in the inflamed lung,http://dx.doi.org/10.1038/mi.2014.129,PMC4430298,25603826,NO-CC CODE,"Much of the biology surrounding macrophage functional specificity has arisen through examining inflammation-induced polarising signals, but this also occurs in homeostasis, requiring tissue-specific environmental triggers that influence macrophage phenotype and function. The TAM receptor family of receptor tyrosine kinases (Tyro3, Axl and MerTK) mediates the non-inflammatory removal of apoptotic cells by phagocytes through the bridging phosphatidylserine-binding molecules Gas6 or Protein S. We show that one such TAM receptor (Axl) is exclusively expressed on mouse airway macrophages, but not interstitial macrophages and other lung leukocytes, under homeostatic conditions and is constitutively ligated to Gas6. Axl expression is potently induced by GM-CSF expressed in the healthy and inflamed airway, and by type I interferon or TLR3 stimulation on human and mouse macrophages, indicating potential involvement of Axl in apoptotic cell removal under inflammatory conditions. Indeed, an absence of Axl does not cause sterile inflammation in health, but leads to exaggerated lung inflammatory disease upon influenza infection. These data imply that Axl allows specific identification of airway macrophages, and that its expression is critical for macrophage functional compartmentalisation in the airspaces or lung interstitium. We propose that this may be a critical feature to prevent excessive inflammation due to secondary necrosis of apoptotic cells that have not been cleared by efferocytosis.",2015 Sep 21,"['Fujimori, Toshifumi', 'Grabiec, Aleksander M', 'Kaur, Manminder', 'Bell, Thomas J', 'Fujino, Naoya', 'Cook, Peter C', 'Svedberg, Freya R', 'MacDonald, Andrew S', 'Maciewicz, Rose A', 'Singh, Dave', 'Hussell, Tracy']",Mucosal Immunol,,,False
ba085942946a4ef42509d21445021f1bcdbe3b7e,PMC,"Cough: neurophysiology, methods of research, pharmacological therapy and phonoaudiology",http://dx.doi.org/10.7162/S1809-97772012000200016,PMC4435438,25991944,NO-CC CODE,"Introduction: The cough is the more common respiratory symptom in children and adults. Objective: To present a revision on the neurophysiology and the methods for study of the consequence of the cough, as well as the pharmacotherapy and phonoaudiology therapy of the cough, based on the works published between 2005 and 2010 and indexed in the bases Medline, Lilacs and Library Cochrane under them to keywords “cough” or “anti-cough”. Synthesis of the data: The consequence of the cough involves activation of receiving multiples becomes vacant in the aerial ways and of neural projections of the nucleus of the solitary treatment for other structures of the central nervous system. Experimental techniques allow studying the consequence of the cough to the cellular and molecular level to develop new anti-cough agents. It does not have evidences of that anti-cough exempt of medical lapsing they have superior effectiveness to the one of placebo for the relief of the cough. The phonoaudiology therapy can benefit patients with refractory chronic cough to the pharmacological treatment, over all when paradoxical movement of the vocal folds coexists. Final Comments: The boarding to multidiscipline has basic paper in the etiological diagnosis and treatment of the cough. The otolaryngologist must inform the patients on the risks of the anti-cough of free sales in order to prevent adverse poisonings and effect, especially in children.",2012 Apr,"Balbani, Aracy Pereira Silveira",Int Arch Otorhinolaryngol,,,True
3800c3eb94b585de91c4c52f585719c0fef6b6bb,PMC,"Acute Middle East Respiratory Syndrome Coronavirus Infection in Livestock Dromedaries, Dubai, 2014",http://dx.doi.org/10.3201/eid2106.150038,PMC4451903,25989145,NO-CC CODE,"Camels carry Middle East respiratory syndrome coronavirus, but little is known about infection age or prevalence. We studied >800 dromedaries of all ages and 15 mother–calf pairs. This syndrome constitutes an acute, epidemic, and time-limited infection in camels <4 years of age, particularly calves. Delayed social separation of calves might reduce human infection risk.",2015 Jun,"['Wernery, Ulrich', 'Corman, Victor M.', 'Wong, Emily Y.M.', 'Tsang, Alan K.L.', 'Muth, Doreen', 'Lau, Susanna K. P.', 'Khazanehdari, Kamal', 'Zirkel, Florian', 'Ali, Mansoor', 'Nagy, Peter', 'Juhasz, Jutka', 'Wernery, Renate', 'Joseph, Sunitha', 'Syriac, Ginu', 'Elizabeth, Shyna K.', 'Patteril, Nissy Annie Georgy', 'Woo, Patrick C. Y.', 'Drosten, Christian']",Emerg Infect Dis,,,True
993145adae199c9f03caa8989e6b82a6e69d2813,PMC,"Ebola Risk Perception in Germany, 2014",http://dx.doi.org/10.3201/eid2106.150013,PMC4451905,25989020,NO-CC CODE,"Ebola virus disease (EVD) outbreaks have occurred during the past 5 decades, but none has affected European countries like the 2014 epidemic in West Africa. We used an online questionnaire to investigate risk perceptions in Germany during this epidemic peak. Our questionnaire covered risk perceptions, knowledge about transmission routes, media use, reactions to the outbreak, attitudes toward measures to prevent the spread of EVD and vaccination against EVD, and willingness to volunteer for aid missions. Of 974 participants, 29% indicated that they worried about EVD, 4% correctly stated virus transmission routes, and 75% incorrectly rated airborne transmission and transmission by asymptomatic patients as possible. Many indicated that if a patient were flown to Germany for treatment in a nearby hospital, they would adapt preventive behavior. Although most participants were not worried about EVD at the current stage of the epidemic, misperceptions regarding transmission were common and could trigger inappropriate behavior changes.",2015 Jun,"['Rübsamen, Nicole', 'Castell, Stefanie', 'Horn, Johannes', 'Karch, André', 'Ott, Jördis J.', 'Raupach-Rosin, Heike', 'Zoch, Beate', 'Krause, Gérard', 'Mikolajczyk, Rafael T.']",Emerg Infect Dis,,,True
837b4d88c47776128f9adede779624245f3e0494,PMC,"Ebola Risk Perception in Germany, 2014",http://dx.doi.org/10.3201/eid2106.150013,PMC4451905,25989020,NO-CC CODE,"Ebola virus disease (EVD) outbreaks have occurred during the past 5 decades, but none has affected European countries like the 2014 epidemic in West Africa. We used an online questionnaire to investigate risk perceptions in Germany during this epidemic peak. Our questionnaire covered risk perceptions, knowledge about transmission routes, media use, reactions to the outbreak, attitudes toward measures to prevent the spread of EVD and vaccination against EVD, and willingness to volunteer for aid missions. Of 974 participants, 29% indicated that they worried about EVD, 4% correctly stated virus transmission routes, and 75% incorrectly rated airborne transmission and transmission by asymptomatic patients as possible. Many indicated that if a patient were flown to Germany for treatment in a nearby hospital, they would adapt preventive behavior. Although most participants were not worried about EVD at the current stage of the epidemic, misperceptions regarding transmission were common and could trigger inappropriate behavior changes.",2015 Jun,"['Rübsamen, Nicole', 'Castell, Stefanie', 'Horn, Johannes', 'Karch, André', 'Ott, Jördis J.', 'Raupach-Rosin, Heike', 'Zoch, Beate', 'Krause, Gérard', 'Mikolajczyk, Rafael T.']",Emerg Infect Dis,,,True
464575e607e642ade630c3c58620fcfea98cf698,PMC,"Pneumonia Outbreak Caused by Chlamydophila pneumoniae among US Air Force Academy Cadets, Colorado, USA",http://dx.doi.org/10.3201/eid2106.141394,PMC4451914,25988545,NO-CC CODE,"During October 2013–May 2014, there were 102 cases of pneumonia diagnosed in US Air Force Academy cadets. A total of 73% of tested nasal washes contained Chlamydophila pneumoniae. This agent can be considered to be present on campus settings during outbreaks with numerous, seemingly disconnected cases of relatively mild pneumonia.",2015 Jun,"['Fajardo, Kevin A.', 'Zorich, Shauna C.', 'Voss, Jameson D.', 'Thervil, Jeffrey W.']",Emerg Infect Dis,,,True
e9e0611bd64fa36c1a87679f24e49e28b92951bc,PMC,Lack of Protection Against Ebola Virus from Chloroquine in Mice and Hamsters,http://dx.doi.org/10.3201/eid2106.150176,PMC4451918,25988934,NO-CC CODE,"The antimalarial drug chloroquine has been suggested as a treatment for Ebola virus infection. Chloroquine inhibited virus replication in vitro, but only at cytotoxic concentrations. In mouse and hamster models, treatment did not improve survival. Chloroquine is not a promising treatment for Ebola. Efforts should be directed toward other drug classes.",2015 Jun,"['Falzarano, Darryl', 'Safronetz, David', 'Prescott, Joseph', 'Marzi, Andrea', 'Feldmann, Friederike', 'Feldmann, Heinz']",Emerg Infect Dis,,,True
ba905b2783008a9ceb817d60ead70d937fb002a4,PMC,"Public health in Canada: Evolution, meaning and a new paradigm for respiratory therapy",,PMC4456826,26078595,NO-CC CODE,"Chronic disease burden in Canada poses an imminent public health threat. The impact of respiratory disease in Canada alone is significant, affecting one in five and leading any other cause of repeat hospitalization in all age groups. Public health action is considered to be an important means of addressing these issues. Historical understanding of health has evolved to support the adoption of paradigms by professions that recognize the limitations of medical intervention in addressing the fundamental basis of disease when compared with the broader public health perspective. Several key historical events have shaped this understanding in the Canadian context including the Lalonde and Epp reports, and public health emergencies such as the severe acute respiratory syndrome outbreak in 2003. The profession of respiratory therapy has historically existed within a medicalized paradigm of practice; however, forces both internal and external to the profession are pressuring it to consider adopting broader social-and population-based approaches. As a rapidly evolving profession, there is a need to explore emerging areas of practice opportunities in the discipline. Investigating alternative knowledge and ideology can ensure that effective strategies for addressing the contemporary respiratory heath needs of Canadians are undertaken. The present article explores the rationale for a public health- and population-based approach to health in general, and its applicability to the respiratory therapist’s role in addressing respiratory health-related issues in Canada.",2013 Winter,"West, Andrew J",Can J Respir Ther,,,True
d5e52547df25abfc489429e1cd693f5c70876de9,PMC,Responding to Ebola: The role of medical journals during global public health emergencies,,PMC4456836,26078612,NO-CC CODE,,2014 Autumn,"Nickerson, Jason",Can J Respir Ther,,,True
535448073c1721a7928c2814283c5cda6e151902,PMC,Saving Human Lives: What Complexity Science and Information Systems can Contribute,http://dx.doi.org/10.1007/s10955-014-1024-9,PMC4457089,26074625,NO-CC CODE,"We discuss models and data of crowd disasters, crime, terrorism, war and disease spreading to show that conventional recipes, such as deterrence strategies, are often not effective and sufficient to contain them. Many common approaches do not provide a good picture of the actual system behavior, because they neglect feedback loops, instabilities and cascade effects. The complex and often counter-intuitive behavior of social systems and their macro-level collective dynamics can be better understood by means of complexity science. We highlight that a suitable system design and management can help to stop undesirable cascade effects and to enable favorable kinds of self-organization in the system. In such a way, complexity science can help to save human lives.",2015 Jun 5,"['Helbing, Dirk', 'Brockmann, Dirk', 'Chadefaux, Thomas', 'Donnay, Karsten', 'Blanke, Ulf', 'Woolley-Meza, Olivia', 'Moussaid, Mehdi', 'Johansson, Anders', 'Krause, Jens', 'Schutte, Sebastian', 'Perc, Matjaž']",J Stat Phys,,,True
b6652aa050955ad84e8a6bc22eb44829bb65dde9,PMC,Preparedness of institutions around the world for managing patients with Ebola virus disease: an infection control readiness checklist,http://dx.doi.org/10.1186/s13756-015-0061-8,PMC4459682,26056563,NO-CC CODE,"BACKGROUND: In response to global concerns about the largest Ebola virus disease (EVD), outbreak to-date in West Africa documented healthcare associated transmission and the risk of global spread, the International Society of Chemotherapy (ISC) Infection Control Working Group created an Ebola Infection Control Readiness Checklist to assess the preparedness of institutions around the globe. We report data from the electronic checklist that was disseminated to medical professionals from October to December 2014 and identify action needed towards better preparedness levels. FINDINGS: Data from 192 medical professionals (one third from Africa) representing 125 hospitals in 45 countries around the globe were obtained through a specifically developed electronic survey. The survey contained 76 specific questions in 7 major sections: Administrative/operational support; Communications; Education and audit; Human resources, Supplies, Infection Prevention and Control practices and Clinical management of patients. The majority of respondents were infectious disease specialists/infection control consultants/clinical microbiologists (75; 39 %), followed by infection control professionals (59; 31 %) and medical doctors of other specialties (17; 9 %). Nearly all (149; 92 %) were directly involved in Ebola preparedness activities. Whilst, 54 % indicated that their hospital would need to handle suspected and proven Ebola cases, the others would subsequently transfer suspected cases to a specialized centre. CONCLUSION: The results from our survey reveal that the general preparedness levels for management of potentially suspected cases of Ebola virus disease is only partially adequate in hospitals. Hospitals designated for admitting EVD suspected and proven patients had more frequently implemented Infection Control preparedness activities than hospitals that would subsequently transfer potential EVD cases to other centres. Results from this first international survey provide a framework for future efforts to improve hospital preparedness worldwide. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13756-015-0061-8) contains supplementary material, which is available to authorized users.",2015 Jun 8,"['Tartari, Ermira', 'Allegranzi, Benedetta', 'Ang, Brenda', 'Calleja, Neville', 'Collignon, Peter', 'Hopman, Joost', 'Lang, Lily', 'Lee, Lai Chee', 'Ling, Moi Lin', 'Mehtar, Shaheen', 'Tambyah, Paul A.', 'Widmer, Andreas', 'Voss, Andreas']",Antimicrob Resist Infect Control,,,False
1b822763c007bb77798727490e95ee2bec342494,PMC,Preparedness of institutions around the world for managing patients with Ebola virus disease: an infection control readiness checklist,http://dx.doi.org/10.1186/s13756-015-0061-8,PMC4459682,26056563,NO-CC CODE,"BACKGROUND: In response to global concerns about the largest Ebola virus disease (EVD), outbreak to-date in West Africa documented healthcare associated transmission and the risk of global spread, the International Society of Chemotherapy (ISC) Infection Control Working Group created an Ebola Infection Control Readiness Checklist to assess the preparedness of institutions around the globe. We report data from the electronic checklist that was disseminated to medical professionals from October to December 2014 and identify action needed towards better preparedness levels. FINDINGS: Data from 192 medical professionals (one third from Africa) representing 125 hospitals in 45 countries around the globe were obtained through a specifically developed electronic survey. The survey contained 76 specific questions in 7 major sections: Administrative/operational support; Communications; Education and audit; Human resources, Supplies, Infection Prevention and Control practices and Clinical management of patients. The majority of respondents were infectious disease specialists/infection control consultants/clinical microbiologists (75; 39 %), followed by infection control professionals (59; 31 %) and medical doctors of other specialties (17; 9 %). Nearly all (149; 92 %) were directly involved in Ebola preparedness activities. Whilst, 54 % indicated that their hospital would need to handle suspected and proven Ebola cases, the others would subsequently transfer suspected cases to a specialized centre. CONCLUSION: The results from our survey reveal that the general preparedness levels for management of potentially suspected cases of Ebola virus disease is only partially adequate in hospitals. Hospitals designated for admitting EVD suspected and proven patients had more frequently implemented Infection Control preparedness activities than hospitals that would subsequently transfer potential EVD cases to other centres. Results from this first international survey provide a framework for future efforts to improve hospital preparedness worldwide. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13756-015-0061-8) contains supplementary material, which is available to authorized users.",2015 Jun 8,"['Tartari, Ermira', 'Allegranzi, Benedetta', 'Ang, Brenda', 'Calleja, Neville', 'Collignon, Peter', 'Hopman, Joost', 'Lang, Lily', 'Lee, Lai Chee', 'Ling, Moi Lin', 'Mehtar, Shaheen', 'Tambyah, Paul A.', 'Widmer, Andreas', 'Voss, Andreas']",Antimicrob Resist Infect Control,,,True
4a228865af2c19adf9386a5b04cca3ceb3c8683d,PMC,Moderate mutation rate in the SARS coronavirus genome and its implications,http://dx.doi.org/10.1186/1471-2148-4-21,PMC446188,15222897,NO-CC CODE,"BACKGROUND: The outbreak of severe acute respiratory syndrome (SARS) caused a severe global epidemic in 2003 which led to hundreds of deaths and many thousands of hospitalizations. The virus causing SARS was identified as a novel coronavirus (SARS-CoV) and multiple genomic sequences have been revealed since mid-April, 2003. After a quiet summer and fall in 2003, the newly emerged SARS cases in Asia, particularly the latest cases in China, are reinforcing a wide-spread belief that the SARS epidemic would strike back. With the understanding that SARS-CoV might be with humans for years to come, knowledge of the evolutionary mechanism of the SARS-CoV, including its mutation rate and emergence time, is fundamental to battle this deadly pathogen. To date, the speed at which the deadly virus evolved in nature and the elapsed time before it was transmitted to humans remains poorly understood. RESULTS: Sixteen complete genomic sequences with available clinical histories during the SARS outbreak were analyzed. After careful examination of multiple-sequence alignment, 114 single nucleotide variations were identified. To minimize the effects of sequencing errors and additional mutations during the cell culture, three strategies were applied to estimate the mutation rate by 1) using the closely related sequences as background controls; 2) adjusting the divergence time for cell culture; or 3) using the common variants only. The mutation rate in the SARS-CoV genome was estimated to be 0.80 – 2.38 × 10(-3 )nucleotide substitution per site per year which is in the same order of magnitude as other RNA viruses. The non-synonymous and synonymous substitution rates were estimated to be 1.16 – 3.30 × 10(-3 )and 1.67 – 4.67 × 10(-3 )per site per year, respectively. The most recent common ancestor of the 16 sequences was inferred to be present as early as the spring of 2002. CONCLUSIONS: The estimated mutation rates in the SARS-CoV using multiple strategies were not unusual among coronaviruses and moderate compared to those in other RNA viruses. All estimates of mutation rates led to the inference that the SARS-CoV could have been with humans in the spring of 2002 without causing a severe epidemic.",2004 Jun 28,"['Zhao, Zhongming', 'Li, Haipeng', 'Wu, Xiaozhuang', 'Zhong, Yixi', 'Zhang, Keqin', 'Zhang, Ya-Ping', 'Boerwinkle, Eric', 'Fu, Yun-Xin']",BMC Evol Biol,,,True
e9c78584c08ba79d735e150eff98297eb57f12dd,PMC,Moderate mutation rate in the SARS coronavirus genome and its implications,http://dx.doi.org/10.1186/1471-2148-4-21,PMC446188,15222897,NO-CC CODE,"BACKGROUND: The outbreak of severe acute respiratory syndrome (SARS) caused a severe global epidemic in 2003 which led to hundreds of deaths and many thousands of hospitalizations. The virus causing SARS was identified as a novel coronavirus (SARS-CoV) and multiple genomic sequences have been revealed since mid-April, 2003. After a quiet summer and fall in 2003, the newly emerged SARS cases in Asia, particularly the latest cases in China, are reinforcing a wide-spread belief that the SARS epidemic would strike back. With the understanding that SARS-CoV might be with humans for years to come, knowledge of the evolutionary mechanism of the SARS-CoV, including its mutation rate and emergence time, is fundamental to battle this deadly pathogen. To date, the speed at which the deadly virus evolved in nature and the elapsed time before it was transmitted to humans remains poorly understood. RESULTS: Sixteen complete genomic sequences with available clinical histories during the SARS outbreak were analyzed. After careful examination of multiple-sequence alignment, 114 single nucleotide variations were identified. To minimize the effects of sequencing errors and additional mutations during the cell culture, three strategies were applied to estimate the mutation rate by 1) using the closely related sequences as background controls; 2) adjusting the divergence time for cell culture; or 3) using the common variants only. The mutation rate in the SARS-CoV genome was estimated to be 0.80 – 2.38 × 10(-3 )nucleotide substitution per site per year which is in the same order of magnitude as other RNA viruses. The non-synonymous and synonymous substitution rates were estimated to be 1.16 – 3.30 × 10(-3 )and 1.67 – 4.67 × 10(-3 )per site per year, respectively. The most recent common ancestor of the 16 sequences was inferred to be present as early as the spring of 2002. CONCLUSIONS: The estimated mutation rates in the SARS-CoV using multiple strategies were not unusual among coronaviruses and moderate compared to those in other RNA viruses. All estimates of mutation rates led to the inference that the SARS-CoV could have been with humans in the spring of 2002 without causing a severe epidemic.",2004 Jun 28,"['Zhao, Zhongming', 'Li, Haipeng', 'Wu, Xiaozhuang', 'Zhong, Yixi', 'Zhang, Keqin', 'Zhang, Ya-Ping', 'Boerwinkle, Eric', 'Fu, Yun-Xin']",BMC Evol Biol,,,True
cdb29ec7a9029d22f6fbf7ee04543819591acdc2,PMC,Moderate mutation rate in the SARS coronavirus genome and its implications,http://dx.doi.org/10.1186/1471-2148-4-21,PMC446188,15222897,NO-CC CODE,"BACKGROUND: The outbreak of severe acute respiratory syndrome (SARS) caused a severe global epidemic in 2003 which led to hundreds of deaths and many thousands of hospitalizations. The virus causing SARS was identified as a novel coronavirus (SARS-CoV) and multiple genomic sequences have been revealed since mid-April, 2003. After a quiet summer and fall in 2003, the newly emerged SARS cases in Asia, particularly the latest cases in China, are reinforcing a wide-spread belief that the SARS epidemic would strike back. With the understanding that SARS-CoV might be with humans for years to come, knowledge of the evolutionary mechanism of the SARS-CoV, including its mutation rate and emergence time, is fundamental to battle this deadly pathogen. To date, the speed at which the deadly virus evolved in nature and the elapsed time before it was transmitted to humans remains poorly understood. RESULTS: Sixteen complete genomic sequences with available clinical histories during the SARS outbreak were analyzed. After careful examination of multiple-sequence alignment, 114 single nucleotide variations were identified. To minimize the effects of sequencing errors and additional mutations during the cell culture, three strategies were applied to estimate the mutation rate by 1) using the closely related sequences as background controls; 2) adjusting the divergence time for cell culture; or 3) using the common variants only. The mutation rate in the SARS-CoV genome was estimated to be 0.80 – 2.38 × 10(-3 )nucleotide substitution per site per year which is in the same order of magnitude as other RNA viruses. The non-synonymous and synonymous substitution rates were estimated to be 1.16 – 3.30 × 10(-3 )and 1.67 – 4.67 × 10(-3 )per site per year, respectively. The most recent common ancestor of the 16 sequences was inferred to be present as early as the spring of 2002. CONCLUSIONS: The estimated mutation rates in the SARS-CoV using multiple strategies were not unusual among coronaviruses and moderate compared to those in other RNA viruses. All estimates of mutation rates led to the inference that the SARS-CoV could have been with humans in the spring of 2002 without causing a severe epidemic.",2004 Jun 28,"['Zhao, Zhongming', 'Li, Haipeng', 'Wu, Xiaozhuang', 'Zhong, Yixi', 'Zhang, Keqin', 'Zhang, Ya-Ping', 'Boerwinkle, Eric', 'Fu, Yun-Xin']",BMC Evol Biol,,,True
433adf76ea9adc9f5c540d4c28142d4d020969e2,PMC,Commensal enteric bacteria lipopolysaccharide impairs host defense against disseminated Candida albicans fungal infection,http://dx.doi.org/10.1038/mi.2014.119,PMC4465067,25492473,NO-CC CODE,"Commensal enteric bacteria maintain systemic immune responsiveness that protects against disseminated or localized infection in extra-intestinal tissues caused by pathogenic microbes. However, since shifts in infection susceptibility after commensal bacteria eradication have primarily been probed using viruses, the broader applicability to other pathogen types remains undefined. In sharp contrast to diminished antiviral immunity, we show commensal bacteria eradication bolsters protection against disseminated Candida albicans fungal infection. Enhanced antifungal immunity reflects more robust systemic expansion of Ly6G(hi)Ly6C(int) neutrophils, and their mobilization into infected tissues among antibiotic treated compared with commensal bacteria replete control mice. Reciprocally, depletion of neutrophils from expanded levels or intestinal LPS reconstitution overrides the antifungal protective benefits conferred by commensal bacteria eradication. This discordance in antifungal compared with antiviral immunity highlights intrinsic differences in how commensal bacteria control responsiveness for specific immune cell subsets because pathogen-specific CD8(+) T cells that protect against viruses were suppressed similarly after C. albicans and influenza A virus infection. Thus, positive calibration of antiviral immunity by commensal bacteria is counterbalanced by restrained activation of other immune components that confer antifungal immunity.",2015 Jul 10,"['Jiang, Tony T.', 'Chaturvedi, Vandana', 'Ertelt, James M.', 'Xin, Lijun', 'Clark, Dayna R.', 'Kinder, Jeremy M.', 'Way, Sing Sing']",Mucosal Immunol,,,True
0c691a912d4d4aeb61226048b724f9e84c77bd1d,PMC,Commensal enteric bacteria lipopolysaccharide impairs host defense against disseminated Candida albicans fungal infection,http://dx.doi.org/10.1038/mi.2014.119,PMC4465067,25492473,NO-CC CODE,"Commensal enteric bacteria maintain systemic immune responsiveness that protects against disseminated or localized infection in extra-intestinal tissues caused by pathogenic microbes. However, since shifts in infection susceptibility after commensal bacteria eradication have primarily been probed using viruses, the broader applicability to other pathogen types remains undefined. In sharp contrast to diminished antiviral immunity, we show commensal bacteria eradication bolsters protection against disseminated Candida albicans fungal infection. Enhanced antifungal immunity reflects more robust systemic expansion of Ly6G(hi)Ly6C(int) neutrophils, and their mobilization into infected tissues among antibiotic treated compared with commensal bacteria replete control mice. Reciprocally, depletion of neutrophils from expanded levels or intestinal LPS reconstitution overrides the antifungal protective benefits conferred by commensal bacteria eradication. This discordance in antifungal compared with antiviral immunity highlights intrinsic differences in how commensal bacteria control responsiveness for specific immune cell subsets because pathogen-specific CD8(+) T cells that protect against viruses were suppressed similarly after C. albicans and influenza A virus infection. Thus, positive calibration of antiviral immunity by commensal bacteria is counterbalanced by restrained activation of other immune components that confer antifungal immunity.",2015 Jul 10,"['Jiang, Tony T.', 'Chaturvedi, Vandana', 'Ertelt, James M.', 'Xin, Lijun', 'Clark, Dayna R.', 'Kinder, Jeremy M.', 'Way, Sing Sing']",Mucosal Immunol,,,False
79b6bbfb34a6b0365ee581d3e057005a67d5f691,PMC,Use of the Fluocinolone Acetonide Intravitreal Implant for the Treatment of Noninfectious Posterior Uveitis: 3-Year Results of a Randomized Clinical Trial in a Predominantly Asian Population,http://dx.doi.org/10.1007/s40123-014-0027-6,PMC4470982,25502122,NO-CC CODE,"INTRODUCTION: The fluocinolone acetonide (FA) intravitreal implant 0.59 mg (Retisert(®), Bausch + Lomb, Rochester, NY, USA) provides sustained release of FA directly to the vitreous cavity over a prolonged period of time. The purpose of this study was to evaluate the safety and efficacy of a 0.59- and 2.1-mg FA intravitreal implant in patients with noninfectious posterior uveitis. METHODS: A prospective, multicenter, randomized, double-masked, dose-controlled study was performed. Patients were randomized to the 0.59- or 2.1-mg FA implant surgically placed in the vitreous cavity through a pars plana incision and were evaluated at visits through 3 years. Patients with bilateral disease had the more severely affected eye implanted. Outcomes included uveitis recurrence rate, best-corrected visual acuity (BCVA), use of adjunctive therapy, and safety. RESULTS: A total of 239 patients, predominantly Asian, were implanted (n = 117, 0.59-mg implant; n = 122, 2.1-mg implant). Approximately 80% of patients had bilateral disease. Recurrence rates for implanted eyes decreased from 42.3% during the 1-year pre-implantation period to 25.9% during the 3-year post-implantation period (P = 0.0003) and increased for nonimplanted fellow eyes from 19.8 to 59.7% (P < 0.0001). More implanted eyes gained ≥3 lines of BCVA compared to nonimplanted fellow eyes (P ≤ 0.0046); and implanted eyes required less adjunctive systemic therapy and fewer periocular injections (P < 0.0001). Elevations of intraocular pressure (≥10 mm Hg) were frequent in implanted eyes (67.8%, 0.59-mg implant; 71.3%, 2.1-mg implant); nearly all (94.9%) phakic implanted eyes required cataract surgery. CONCLUSION: The FA intravitreal implant significantly reduced uveitis recurrence rates and led to improvements in visual acuity and reductions in adjunctive therapy. Lens clarity and intraocular pressure require monitoring. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40123-014-0027-6) contains supplementary material, which is available to authorized users.",2015 Jun 12,"['Sangwan, Virender S.', 'Pearson, P. Andrew', 'Paul, Hemanth', 'Comstock, Timothy L.']",Ophthalmol Ther,,,False
82722b89a6c49087f09c56d5d6b58e2bfe33bc7e,PMC,Use of the Fluocinolone Acetonide Intravitreal Implant for the Treatment of Noninfectious Posterior Uveitis: 3-Year Results of a Randomized Clinical Trial in a Predominantly Asian Population,http://dx.doi.org/10.1007/s40123-014-0027-6,PMC4470982,25502122,NO-CC CODE,"INTRODUCTION: The fluocinolone acetonide (FA) intravitreal implant 0.59 mg (Retisert(®), Bausch + Lomb, Rochester, NY, USA) provides sustained release of FA directly to the vitreous cavity over a prolonged period of time. The purpose of this study was to evaluate the safety and efficacy of a 0.59- and 2.1-mg FA intravitreal implant in patients with noninfectious posterior uveitis. METHODS: A prospective, multicenter, randomized, double-masked, dose-controlled study was performed. Patients were randomized to the 0.59- or 2.1-mg FA implant surgically placed in the vitreous cavity through a pars plana incision and were evaluated at visits through 3 years. Patients with bilateral disease had the more severely affected eye implanted. Outcomes included uveitis recurrence rate, best-corrected visual acuity (BCVA), use of adjunctive therapy, and safety. RESULTS: A total of 239 patients, predominantly Asian, were implanted (n = 117, 0.59-mg implant; n = 122, 2.1-mg implant). Approximately 80% of patients had bilateral disease. Recurrence rates for implanted eyes decreased from 42.3% during the 1-year pre-implantation period to 25.9% during the 3-year post-implantation period (P = 0.0003) and increased for nonimplanted fellow eyes from 19.8 to 59.7% (P < 0.0001). More implanted eyes gained ≥3 lines of BCVA compared to nonimplanted fellow eyes (P ≤ 0.0046); and implanted eyes required less adjunctive systemic therapy and fewer periocular injections (P < 0.0001). Elevations of intraocular pressure (≥10 mm Hg) were frequent in implanted eyes (67.8%, 0.59-mg implant; 71.3%, 2.1-mg implant); nearly all (94.9%) phakic implanted eyes required cataract surgery. CONCLUSION: The FA intravitreal implant significantly reduced uveitis recurrence rates and led to improvements in visual acuity and reductions in adjunctive therapy. Lens clarity and intraocular pressure require monitoring. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40123-014-0027-6) contains supplementary material, which is available to authorized users.",2015 Jun 12,"['Sangwan, Virender S.', 'Pearson, P. Andrew', 'Paul, Hemanth', 'Comstock, Timothy L.']",Ophthalmol Ther,,,True
39baa82181ff59bba638bda992aafd22b41e4abe,PMC,"Evaluation of Patients under Investigation for MERS-CoV Infection, United States, January 2013–October 2014",http://dx.doi.org/10.3201/eid2107.141888,PMC4480388,26079433,NO-CC CODE,"Middle East respiratory syndrome (MERS) cases continue to be reported from the Middle East. Evaluation and testing of patients under investigation (PUIs) for MERS are recommended. In 2013–2014, two imported cases were detected among 490 US PUIs. Continued awareness is needed for early case detection and implementation of infection control measures.",2015 Jul,"['Schneider, Eileen', 'Chommanard, Christina', 'Rudd, Jessica', 'Whitaker, Brett', 'Lowe, Luis', 'Gerber, Susan I.']",Emerg Infect Dis,,,True
fc6ab4b693bda93d6d96fed4c7ffba6510d04e0e,PMC,"Lack of Transmission among Close Contacts of Patient with Case of Middle East Respiratory Syndrome Imported into the United States, 2014",http://dx.doi.org/10.3201/eid2107.150054,PMC4480394,26079176,NO-CC CODE,"In May 2014, a traveler from the Kingdom of Saudi Arabia was the first person identified with Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States. To evaluate transmission risk, we determined the type, duration, and frequency of patient contact among health care personnel (HCP), household, and community contacts by using standard questionnaires and, for HCP, global positioning system (GPS) tracer tag logs. Respiratory and serum samples from all contacts were tested for MERS-CoV. Of 61 identified contacts, 56 were interviewed. HCP exposures occurred most frequently in the emergency department (69%) and among nurses (47%); some HCP had contact with respiratory secretions. Household and community contacts had brief contact (e.g., hugging). All laboratory test results were negative for MERS-CoV. This contact investigation found no secondary cases, despite case-patient contact by 61 persons, and provides useful information about MERS-CoV transmission risk. Compared with GPS tracer tag recordings, self-reported contact may not be as accurate.",2015 Jul,"['Breakwell, Lucy', 'Pringle, Kimberly', 'Chea, Nora', 'Allen, Donna', 'Allen, Steve', 'Richards, Shawn', 'Pantones, Pam', 'Sandoval, Michelle', 'Liu, Lixia', 'Vernon, Michael', 'Conover, Craig', 'Chugh, Rashmi', 'DeMaria, Alfred', 'Burns, Rachel', 'Smole, Sandra', 'Gerber, Susan I.', 'Cohen, Nicole J', 'Kuhar, David', 'Haynes, Lia M.', 'Schneider, Eileen', 'Kumar, Alan', 'Kapoor, Minal', 'Madrigal, Marlene', 'Swerdlow, David L.', 'Feikin, Daniel R.']",Emerg Infect Dis,,,True
9250bb5a4c335bb86319f5e922698816625c40d8,PMC,"MERS-CoV in Upper Respiratory Tract and Lungs of Dromedary Camels, Saudi Arabia, 2013–2014",http://dx.doi.org/10.3201/eid2107.150070,PMC4480395,26079346,NO-CC CODE,"To assess the temporal dynamics of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in dromedary camels, specimens were collected at 1–2 month intervals from 2 independent groups of animals during April 2013–May 2014 in Al-Ahsa Province, Saudi Arabia, and tested for MERS-CoV RNA by reverse transcription PCR. Of 96 live camels, 28 (29.2%) nasal swab samples were positive; of 91 camel carcasses, 56 (61.5%) lung tissue samples were positive. Positive samples were more commonly found among young animals (<4 years of age) than adults (>4 years of age). The proportions of positive samples varied by month for both groups; detection peaked during November 2013 and January 2014 and declined in March and May 2014. These findings further our understanding of MERS-CoV infection in dromedary camels and may help inform intervention strategies to reduce zoonotic infections.",2015 Jul,"['Khalafalla, Abdelmalik I.', 'Lu, Xiaoyan', 'Al-Mubarak, Abdullah I.A.', 'Dalab, Abdul Hafeed S.', 'Al-Busadah, Khalid A.S.', 'Erdman, Dean D.']",Emerg Infect Dis,,,True
e194924017ffd82f926955f23ca6e30ef772b6de,PMC,"Absence of MERS-Coronavirus in Bactrian Camels, Southern Mongolia, November 2014",http://dx.doi.org/10.3201/eid2107.150178,PMC4480398,26080032,NO-CC CODE,,2015 Jul,"['Chan, Samuel M.S.', 'Damdinjav, Batchuluun', 'Perera, Ranawaka A.P.M.', 'Chu, Daniel K.W.', 'Khishgee, Bodisaikhan', 'Enkhbold, Bazarragchaa', 'Poon, Leo L.M.', 'Peiris, Malik']",Emerg Infect Dis,,,True
4b452b0428ac7d2aaeaa1b4c313e834e2461e11b,PMC,Function-Based Mutation-Resistant Synthetic Signaling Device Activated by HIV-1 Proteolysis,http://dx.doi.org/10.1021/sb5002483,PMC4487218,25393958,NO-CC CODE,"[Image: see text] The high mutation rate of the human immunodeficiency virus type 1 (HIV-1) virus is a major problem since it evades the function of antibodies and chemical inhibitors. Here, we demonstrate a viral detection strategy based on synthetic biology principles to detect a specific viral function rather than a particular viral protein. The resistance caused by mutations can be circumvented since the mutations that cause the loss of function also incapacitate the virus. Many pathogens encode proteases that are essential for their replication and that have a defined substrate specificity. A genetically encoded sensor composed of a fused membrane anchor, viral protease target site, and an orthogonal transcriptional activator was engineered into a human cell line. The HIV-1 protease released the transcriptional activator from the membrane, thereby inducing transcription of the selected genes. The device was still strongly activated by clinically relevant protease mutants that are resistant to protease inhibitors. In the future, a similar principle could be applied to detect also other pathogens and functions.",2015 Jun 19,"['Majerle, Andreja', 'Gaber, Rok', 'Benčina, Mojca', 'Jerala, Roman']",ACS Synth Biol,,,True
99f11f6e7dcf626abe3290b0cdc98d91e291517a,PMC,Function-Based Mutation-Resistant Synthetic Signaling Device Activated by HIV-1 Proteolysis,http://dx.doi.org/10.1021/sb5002483,PMC4487218,25393958,NO-CC CODE,"[Image: see text] The high mutation rate of the human immunodeficiency virus type 1 (HIV-1) virus is a major problem since it evades the function of antibodies and chemical inhibitors. Here, we demonstrate a viral detection strategy based on synthetic biology principles to detect a specific viral function rather than a particular viral protein. The resistance caused by mutations can be circumvented since the mutations that cause the loss of function also incapacitate the virus. Many pathogens encode proteases that are essential for their replication and that have a defined substrate specificity. A genetically encoded sensor composed of a fused membrane anchor, viral protease target site, and an orthogonal transcriptional activator was engineered into a human cell line. The HIV-1 protease released the transcriptional activator from the membrane, thereby inducing transcription of the selected genes. The device was still strongly activated by clinically relevant protease mutants that are resistant to protease inhibitors. In the future, a similar principle could be applied to detect also other pathogens and functions.",2015 Jun 19,"['Majerle, Andreja', 'Gaber, Rok', 'Benčina, Mojca', 'Jerala, Roman']",ACS Synth Biol,,,True
5b009eb5287c8b9045f32c4e180f1cce5105f52d,PMC,"Year in review in Intensive Care Medicine 2014: III. Severe infections, septic shock, healthcare-associated infections, highly resistant bacteria, invasive fungal infections, severe viral infections, Ebola virus disease and paediatrics",http://dx.doi.org/10.1007/s00134-015-3755-8,PMC4491096,25810214,NO-CC CODE,,2015 Mar 26,"['Timsit, Jean-François', 'Perner, Anders', 'Bakker, Jan', 'Bassetti, Matteo', 'Benoit, Dominique', 'Cecconi, Maurizio', 'Randall Curtis, J.', 'Doig, Gordon S.', 'Herridge, Margaret', 'Jaber, Samir', 'Joannidis, Michael', 'Papazian, Laurent', 'Peters, Mark J.', 'Singer, Pierre', 'Smith, Martin', 'Soares, Marcio', 'Torres, Antoni', 'Vieillard-Baron, Antoine', 'Citerio, Giuseppe', 'Azoulay, Elie']",Intensive Care Med,,,True
22c981d032c93d30406d585ce81ba5d8dc4fda31,PMC,"Design, synthesis, antiviral and cytotoxic evaluation of novel acyclic phosphonate nucleotide analogues with a 5,6-dihydro-1H-[1,2,3]triazolo[4,5-d]pyridazine-4,7-dione system",http://dx.doi.org/10.1007/s00706-013-1137-x,PMC4494773,26166892,NO-CC CODE,"ABSTRACT: A series of diethyl 2-(4,5-dimethoxycarbonyl-1H-1,2,3-triazol-1-yl)alkylphosphonates was synthesised from ω-azidoalkylphosphonates and dimethyl acetylenedicarboxylate and was further transformed into the respective diamides, dihydrazides, and 5,6-dihydro-1H-[1,2,3]triazolo[4,5-d]pyridazine-4,7-diones as phosphonate analogues of acyclic nucleosides having nucleobases replaced with substituted 1,2,3-triazoles. All compounds containing P–C–C–triazole or P–C–C–CH(2)–triazole moieties exist in single conformations in which the diethoxyphosphoryl and substituted 1,2,3-triazolyl or substituted (1,2,3-triazolyl)methyl groups are oriented anti. All phosphonates were evaluated in vitro for activity against a variety of DNA and RNA viruses. None of the compounds were endowed with antiviral activity. They were not cytostatic at 100 μM. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00706-013-1137-x) contains supplementary material, which is available to authorized users.",2014 Jan 25,"['Bankowska, Emilia', 'Balzarini, Jan', 'Głowacka, Iwona E.', 'Wróblewski, Andrzej E.']",Monatsh Chem,,,False
9e27ba9881ed5c007ce21a415db956db0755e1f4,PMC,"Design, synthesis, antiviral and cytotoxic evaluation of novel acyclic phosphonate nucleotide analogues with a 5,6-dihydro-1H-[1,2,3]triazolo[4,5-d]pyridazine-4,7-dione system",http://dx.doi.org/10.1007/s00706-013-1137-x,PMC4494773,26166892,NO-CC CODE,"ABSTRACT: A series of diethyl 2-(4,5-dimethoxycarbonyl-1H-1,2,3-triazol-1-yl)alkylphosphonates was synthesised from ω-azidoalkylphosphonates and dimethyl acetylenedicarboxylate and was further transformed into the respective diamides, dihydrazides, and 5,6-dihydro-1H-[1,2,3]triazolo[4,5-d]pyridazine-4,7-diones as phosphonate analogues of acyclic nucleosides having nucleobases replaced with substituted 1,2,3-triazoles. All compounds containing P–C–C–triazole or P–C–C–CH(2)–triazole moieties exist in single conformations in which the diethoxyphosphoryl and substituted 1,2,3-triazolyl or substituted (1,2,3-triazolyl)methyl groups are oriented anti. All phosphonates were evaluated in vitro for activity against a variety of DNA and RNA viruses. None of the compounds were endowed with antiviral activity. They were not cytostatic at 100 μM. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00706-013-1137-x) contains supplementary material, which is available to authorized users.",2014 Jan 25,"['Bankowska, Emilia', 'Balzarini, Jan', 'Głowacka, Iwona E.', 'Wróblewski, Andrzej E.']",Monatsh Chem,,,True
22e1dd30a5cbd30d28a4d121e4876c8e327f027e,PMC,Transmissible Gastroenteritis Virus (TGEV) Infection Alters the Expression of Cellular MicroRNA Species That Affect Transcription of TGEV Gene 7,http://dx.doi.org/10.7150/ijbs.11585,PMC4495409,26157346,NO-CC CODE,"Transmissible gastroenteritis virus (TGEV) is a member of Coronaviridae family. TGEV infection has emerged as a major cause of severe gastroenteritis and leads to alterations of many cellular processes. Meanwhile, the pathogenic mechanism of TGEV is still unclear. microRNAs (miRNAs) are a novel class of small non-coding RNAs which are involved in the regulation of numerous biological processes such as viral infection and cell apoptosis. Accumulating data show that miRNAs are involved in the process of coronavirus infection such as replication of severe acute respiratory syndrome coronavirus (SARS-CoV). However, the link between miRNAs and TGEV infection is unknown. In this study, we performed microRNA microarray assay and predicted targets of altered miRNAs. The results showed TGEV infection caused the change of miRNAs profile. Then we selected miR-4331 for further analysis and subsequently identified cell division cycle-associated protein 7 (CDCA7) as the target of miR-4331. Moreover, miR-4331 showed the ability to inhibit transcription of TGEV gene 7 (a non-structure gene) via directly targeting CDCA7. In conclusion, differentially expressed miR-4331 that is caused by TGEV infection can suppress transcription of TGEV gene 7 via targeting cellular CDCA7. Our key finding is that TGEV selectively manipulates the expression of some cellular miRNAs to regulate its subgenomic transcription.",2015 Jun 7,"['Song, Xiangjun', 'Zhao, Xiaomin', 'Huang, Yong', 'Xiang, Hailing', 'Zhang, Wenlong', 'Tong, Dewen']",Int J Biol Sci,,,True
eb25ca46c7e411e952c63ded8455c9df1006bbd4,PMC,Mouse models with human immunity and their application in biomedical research,http://dx.doi.org/10.1111/j.1582-4934.2008.00347.x,PMC4496103,18419795,NO-CC CODE,"Biomedical research in human beings is largely restricted to in vitro studies that lack complexity of a living organism. To overcome this limitation, humanized mouse models are developed based on immunodeficient characteristics of severe combined immunodeficiency (SCID) or recombination activating gene (Rag)(null) mice, which can accept xenografts. Peripheral constitution of human immunity in SCID or Rag(null) mice has been achieved by transplantation of mature human immune cells, foetal human thymus, bone marrow, liver tissues, lymph nodes or a combination of these, although efficiency needs to be improved. These mouse models with constituted human immunity (defined as humanized mice in the present text) have been widely used to investigate the basic principles of human immunobiology as well as complex pathomechanisms and potential therapies of human diseases. Here, elements of an ideal humanized mouse model are highlighted including genetic and non-genetic modification of recipient mice, transplantation strategies and proposals to improve engraftments. The applications of the humanized mice to study the development and response of human immune cells, human autoimmune diseases, virus infections, transplantation biology and tumour biology are reviewed as well.",2009 Jun 15,"['Zhang, Baojun', 'Duan, Ziyuan', 'Zhao, Yong']",J Cell Mol Med,,,True
7e136fdfc76cd52435cf224414e8a59fa3eaf227,PMC,Human Immunodeficiency Virus-Associated Diarrhea: Still an Issue in the Era of Antiretroviral Therapy,http://dx.doi.org/10.1007/s10620-015-3615-y,PMC4499110,25772777,NO-CC CODE,"Over half of patients with human immunodeficiency virus (HIV) experience diarrhea that contributes negatively to quality of life and adherence to antiretroviral therapy (ART). Opportunistic infectious agents that cause diarrhea in patients with HIV span the array of protozoa, fungi, viruses, and bacteria. With global use of ART, the incidence of diarrhea because of opportunistic infections has decreased; however, the incidence of noninfectious diarrhea has increased. The etiology of noninfectious diarrhea in patients with HIV is multifactorial and includes ART-associated diarrhea and gastrointestinal damage related to HIV infection (i.e., HIV enteropathy). A basic algorithm for the diagnosis of diarrhea in patients with HIV includes physical examination, a review of medical history, assessment of HIV viral load and CD4+ T cell count, stool microbiologic assessment, and endoscopic evaluation, if needed. For patients with negative diagnostic results, the diagnosis of noninfectious diarrhea may be considered. Pharmacologic options for the treatment of noninfectious diarrhea are primarily supportive; however, the use of many unapproved agents is based on unstudied and anecdotal information. In addition, these agents can be associated with treatment-limiting adverse events (AEs), such as drug–drug interactions with ART regimens, abuse liability, and additional gastrointestinal AEs. Currently, crofelemer, an antisecretory agent, is the only therapy approved in the USA for the symptomatic relief of noninfectious diarrhea in patients with HIV on ART.",2015 Mar 14,"['Dikman, Andrew E.', 'Schonfeld, Emily', 'Srisarajivakul, Nalinee C.', 'Poles, Michael A.']",Dig Dis Sci,,,True
b029cd7b3c8216e1e78a56afcc5ed30fdc8d812d,PMC,Hospital Resource Utilization and Patient Outcomes Associated with Respiratory Viral Testing in Hospitalized Patients,http://dx.doi.org/10.3201/eid2108.140978,PMC4517710,26197268,NO-CC CODE,"Testing patients for respiratory viruses should guide isolation precautions and provide a rationale for antimicrobial drug therapies, but few studies have evaluated these assumptions. To determine the association between viral testing, patient outcomes, and care processes, we identified adults hospitalized with respiratory symptoms from 2004 through 2012 at a large, academic, tertiary hospital in Canada. Viral testing was performed in 11% (2,722/24,567) of hospital admissions and was not associated with reduced odds for death (odds ratio 0.90, 95% CI 0.76–1.10) or longer length of stay (+1 day for those tested). Viral testing resulted in more resource utilization, including intensive care unit admission, but positive test results were not associated with less antibiotic use or shorter duration of isolation. Results suggest that health care providers do not use viral test results in making management decisions at this hospital. Further research is needed to evaluate the effectiveness of respiratory infection control policies.",2015 Aug,"['Mulpuru, Sunita', 'Aaron, Shawn D.', 'Ronksley, Paul E.', 'Lawrence, Nadine', 'Forster, Alan J.']",Emerg Infect Dis,,,True
2bb74ba71323457fe9d1cf89239595dde6cc0e5e,PMC,Hospital Resource Utilization and Patient Outcomes Associated with Respiratory Viral Testing in Hospitalized Patients,http://dx.doi.org/10.3201/eid2108.140978,PMC4517710,26197268,NO-CC CODE,"Testing patients for respiratory viruses should guide isolation precautions and provide a rationale for antimicrobial drug therapies, but few studies have evaluated these assumptions. To determine the association between viral testing, patient outcomes, and care processes, we identified adults hospitalized with respiratory symptoms from 2004 through 2012 at a large, academic, tertiary hospital in Canada. Viral testing was performed in 11% (2,722/24,567) of hospital admissions and was not associated with reduced odds for death (odds ratio 0.90, 95% CI 0.76–1.10) or longer length of stay (+1 day for those tested). Viral testing resulted in more resource utilization, including intensive care unit admission, but positive test results were not associated with less antibiotic use or shorter duration of isolation. Results suggest that health care providers do not use viral test results in making management decisions at this hospital. Further research is needed to evaluate the effectiveness of respiratory infection control policies.",2015 Aug,"['Mulpuru, Sunita', 'Aaron, Shawn D.', 'Ronksley, Paul E.', 'Lawrence, Nadine', 'Forster, Alan J.']",Emerg Infect Dis,,,False
86d0072187f1f6d092ce296b13d3cb6fae55e70c,PMC,Human–Bat Interactions in Rural West Africa,http://dx.doi.org/10.3201/eid2108.142015,PMC4517717,26177344,NO-CC CODE,"Because some bats host viruses with zoonotic potential, we investigated human–bat interactions in rural Ghana during 2011–2012. Nearly half (46.6%) of respondents regularly visited bat caves; 37.4% had been bitten, scratched, or exposed to bat urine; and 45.6% ate bat meat. Human–bat interactions in rural Ghana are frequent and diverse.",2015 Aug,"['Anti, Priscilla', 'Owusu, Michael', 'Agbenyega, Olivia', 'Annan, Augustina', 'Badu, Ebenezer Kofi', 'Nkrumah, Evans Ewald', 'Tschapka, Marco', 'Oppong, Samuel', 'Adu-Sarkodie, Yaw', 'Drosten, Christian']",Emerg Infect Dis,,,True
d12f22eb235332248406e89f3badacc97a0c2cbc,PMC,Human–Bat Interactions in Rural West Africa,http://dx.doi.org/10.3201/eid2108.142015,PMC4517717,26177344,NO-CC CODE,"Because some bats host viruses with zoonotic potential, we investigated human–bat interactions in rural Ghana during 2011–2012. Nearly half (46.6%) of respondents regularly visited bat caves; 37.4% had been bitten, scratched, or exposed to bat urine; and 45.6% ate bat meat. Human–bat interactions in rural Ghana are frequent and diverse.",2015 Aug,"['Anti, Priscilla', 'Owusu, Michael', 'Agbenyega, Olivia', 'Annan, Augustina', 'Badu, Ebenezer Kofi', 'Nkrumah, Evans Ewald', 'Tschapka, Marco', 'Oppong, Samuel', 'Adu-Sarkodie, Yaw', 'Drosten, Christian']",Emerg Infect Dis,,,True
fbe7dbef085278229c19cf79fc2c5590495960f5,PMC,"Occupational Exposure to Dromedaries and Risk for MERS-CoV Infection, Qatar, 2013–2014",http://dx.doi.org/10.3201/eid2108.150481,PMC4517733,26196891,NO-CC CODE,"We determined the presence of neutralizing antibodies to Middle East respiratory syndrome coronavirus in persons in Qatar with and without dromedary contact. Antibodies were only detected in those with contact, suggesting dromedary exposure as a risk factor for infection. Findings also showed evidence for substantial underestimation of the infection in populations at risk in Qatar.",2015 Aug,"['Reusken, Chantal B.E.M.', 'Farag, Elmoubasher A.B.A.', 'Haagmans, Bart L.', 'Mohran, Khaled A.', 'Godeke, Gert-Jan', 'Raj, Stalin', 'Alhajri, Farhoud', 'Al-Marri, Salih A.', 'Al-Romaihi, Hamad E.', 'Al-Thani, Mohamed', 'Bosch, Berend-Jan', 'van der Eijk, Annemiek A.', 'El-Sayed, Ahmed M.', 'Ibrahim, Adel K.', 'Al-Molawi, N.', 'Müller, Marcel A.', 'Pasha, Syed K.', 'Drosten, Christian', 'AlHajri, Mohd M.', 'Koopmans, Marion P.G.']",Emerg Infect Dis,,,True
5bfde8cd6b202751b2fd6915fc3ffb256b846ec5,PMC,"Occupational Exposure to Dromedaries and Risk for MERS-CoV Infection, Qatar, 2013–2014",http://dx.doi.org/10.3201/eid2108.150481,PMC4517733,26196891,NO-CC CODE,"We determined the presence of neutralizing antibodies to Middle East respiratory syndrome coronavirus in persons in Qatar with and without dromedary contact. Antibodies were only detected in those with contact, suggesting dromedary exposure as a risk factor for infection. Findings also showed evidence for substantial underestimation of the infection in populations at risk in Qatar.",2015 Aug,"['Reusken, Chantal B.E.M.', 'Farag, Elmoubasher A.B.A.', 'Haagmans, Bart L.', 'Mohran, Khaled A.', 'Godeke, Gert-Jan', 'Raj, Stalin', 'Alhajri, Farhoud', 'Al-Marri, Salih A.', 'Al-Romaihi, Hamad E.', 'Al-Thani, Mohamed', 'Bosch, Berend-Jan', 'van der Eijk, Annemiek A.', 'El-Sayed, Ahmed M.', 'Ibrahim, Adel K.', 'Al-Molawi, N.', 'Müller, Marcel A.', 'Pasha, Syed K.', 'Drosten, Christian', 'AlHajri, Mohd M.', 'Koopmans, Marion P.G.']",Emerg Infect Dis,,,True
a14cdb0e8beba648720b8bde6e97915fcaae0142,PMC,Estimates of Outbreak Risk from New Introductions of Ebola with Immediate and Delayed Transmission Control,http://dx.doi.org/10.3201/eid2108.150170,PMC4517734,26196264,NO-CC CODE,"While the ongoing Ebola outbreak continues in the West Africa countries of Guinea, Sierra Leone, and Liberia, health officials elsewhere prepare for new introductions of Ebola from infected evacuees or travelers. We analyzed transmission data from patients (i.e., evacuees, international travelers, and those with locally acquired illness) in countries other than the 3 with continuing Ebola epidemics and quantitatively assessed the outbreak risk from new introductions by using different assumptions for transmission control (i.e., immediate and delayed). Results showed that, even in countries that can quickly limit expected number of transmissions per case to <1, the probability that a single introduction will lead to a substantial number of transmissions is not negligible, particularly if transmission variability is high. Identifying incoming infected travelers before symptom onset can decrease worst-case outbreak sizes more than reducing transmissions from patients with locally acquired cases, but performing both actions can have a synergistic effect.",2015 Aug,"['Toth, Damon J.A.', 'Gundlapalli, Adi V.', 'Khader, Karim', 'Pettey, Warren B.P.', 'Rubin, Michael A.', 'Adler, Frederick R.', 'Samore, Matthew H.']",Emerg Infect Dis,,,True
78e7570c26bdf3477fad36eed435207dffe21305,PMC,Estimates of Outbreak Risk from New Introductions of Ebola with Immediate and Delayed Transmission Control,http://dx.doi.org/10.3201/eid2108.150170,PMC4517734,26196264,NO-CC CODE,"While the ongoing Ebola outbreak continues in the West Africa countries of Guinea, Sierra Leone, and Liberia, health officials elsewhere prepare for new introductions of Ebola from infected evacuees or travelers. We analyzed transmission data from patients (i.e., evacuees, international travelers, and those with locally acquired illness) in countries other than the 3 with continuing Ebola epidemics and quantitatively assessed the outbreak risk from new introductions by using different assumptions for transmission control (i.e., immediate and delayed). Results showed that, even in countries that can quickly limit expected number of transmissions per case to <1, the probability that a single introduction will lead to a substantial number of transmissions is not negligible, particularly if transmission variability is high. Identifying incoming infected travelers before symptom onset can decrease worst-case outbreak sizes more than reducing transmissions from patients with locally acquired cases, but performing both actions can have a synergistic effect.",2015 Aug,"['Toth, Damon J.A.', 'Gundlapalli, Adi V.', 'Khader, Karim', 'Pettey, Warren B.P.', 'Rubin, Michael A.', 'Adler, Frederick R.', 'Samore, Matthew H.']",Emerg Infect Dis,,,True
549932f86b8f9e52e990b8e0b85db63bdd48ac0e,PMC,Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV),http://dx.doi.org/10.1007/s15010-015-0720-y,PMC4521086,25600929,NO-CC CODE,"BACKGROUND: Since the identification of the first case of infection with the Middle East respiratory syndrome corona virus (MERS-CoV) in Saudi Arabia in June 2012, the number of laboratory-confirmed cases has exceeded 941 cases globally, of which 347 died. The disease presents as severe respiratory infection often with shock, acute kidney injury, and coagulopathy. Recently, we observed three cases who presented with neurologic symptoms. These are so far the first reported cases of neurologic injury associated with MERS-CoV infection. METHODS: Data was retrospectively collected from three patients admitted with MERS-CoV infection to Intensive Care unit (ICU) at King Abdulaziz Medical City, Riyadh. They were managed separately in three different wards prior to their admission to ICU. FINDING: The three patients presented with severe neurologic syndrome which included altered level of consciousness ranging from confusion to coma, ataxia, and focal motor deficit. Brain MRI revealed striking changes characterized by widespread, bilateral hyperintense lesions on T2-weighted imaging within the white matter and subcortical areas of the frontal, temporal, and parietal lobes, the basal ganglia, and corpus callosum. None of the lesions showed gadolinium enhancement. INTERPRETATION: CNS involvement should be considered in patients with MERS-CoV and progressive neurological disease, and further elucidation of the pathophysiology of this virus is needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s15010-015-0720-y) contains supplementary material, which is available to authorized users.",2015 Jan 20,"['Arabi, Y. M.', 'Harthi, A.', 'Hussein, J.', 'Bouchama, A.', 'Johani, S.', 'Hajeer, A. H.', 'Saeed, B. T.', 'Wahbi, A.', 'Saedy, A.', 'AlDabbagh, T.', 'Okaili, R.', 'Sadat, M.', 'Balkhy, H.']",Infection,,,True
0f3ba0147ba55673ad30d983c9c850e0e327d1cd,PMC,Twenty Years of Active Bacterial Core Surveillance,http://dx.doi.org/10.3201/eid2109.141333,PMC4550139,26292067,NO-CC CODE,"Active Bacterial Core surveillance (ABCs) was established in 1995 as part of the Centers for Disease Control and Prevention Emerging Infections Program (EIP) network to assess the extent of invasive bacterial infections of public health importance. ABCs is distinctive among surveillance systems because of its large, population-based, geographically diverse catchment area; active laboratory-based identification of cases to ensure complete case capture; detailed collection of epidemiologic information paired with laboratory isolates; infrastructure that allows for more in-depth investigations; and sustained commitment of public health, academic, and clinical partners to maintain the system. ABCs has directly affected public health policies and practices through the development and evaluation of vaccines and other prevention strategies, the monitoring of antimicrobial drug resistance, and the response to public health emergencies and other emerging infections.",2015 Sep,"['Langley, Gayle', 'Schaffner, William', 'Farley, Monica M.', 'Lynfield, Ruth', 'Bennett, Nancy M.', 'Reingold, Arthur', 'Thomas, Ann', 'Harrison, Lee H.', 'Nichols, Megin', 'Petit, Susan', 'Miller, Lisa', 'Moore, Matthew R.', 'Schrag, Stephanie J.', 'Lessa, Fernanda C.', 'Skoff, Tami H.', 'MacNeil, Jessica R.', 'Briere, Elizabeth C.', 'Weston, Emily J.', 'Van Beneden, Chris']",Emerg Infect Dis,,,True
9b75fe020ec7b8a5ee0399a61135cbdfe18a50f8,PMC,Twenty Years of Active Bacterial Core Surveillance,http://dx.doi.org/10.3201/eid2109.141333,PMC4550139,26292067,NO-CC CODE,"Active Bacterial Core surveillance (ABCs) was established in 1995 as part of the Centers for Disease Control and Prevention Emerging Infections Program (EIP) network to assess the extent of invasive bacterial infections of public health importance. ABCs is distinctive among surveillance systems because of its large, population-based, geographically diverse catchment area; active laboratory-based identification of cases to ensure complete case capture; detailed collection of epidemiologic information paired with laboratory isolates; infrastructure that allows for more in-depth investigations; and sustained commitment of public health, academic, and clinical partners to maintain the system. ABCs has directly affected public health policies and practices through the development and evaluation of vaccines and other prevention strategies, the monitoring of antimicrobial drug resistance, and the response to public health emergencies and other emerging infections.",2015 Sep,"['Langley, Gayle', 'Schaffner, William', 'Farley, Monica M.', 'Lynfield, Ruth', 'Bennett, Nancy M.', 'Reingold, Arthur', 'Thomas, Ann', 'Harrison, Lee H.', 'Nichols, Megin', 'Petit, Susan', 'Miller, Lisa', 'Moore, Matthew R.', 'Schrag, Stephanie J.', 'Lessa, Fernanda C.', 'Skoff, Tami H.', 'MacNeil, Jessica R.', 'Briere, Elizabeth C.', 'Weston, Emily J.', 'Van Beneden, Chris']",Emerg Infect Dis,,,True
0cb9fd10d6764d4a7400fe3efb76ee44955eba4c,PMC,"Follow-up of Contacts of Middle East Respiratory Syndrome Coronavirus–Infected Returning Travelers, the Netherlands, 2014",http://dx.doi.org/10.3201/eid2109.150560,PMC4550153,26291986,NO-CC CODE,Notification of 2 imported cases of infection with Middle East respiratory syndrome coronavirus in the Netherlands triggered comprehensive monitoring of contacts. Observed low rates of virus transmission and the psychological effect of contact monitoring indicate that thoughtful assessment of close contacts is prudent and must be guided by clinical and epidemiologic risk factors.,2015 Sep,"['Mollers, Madelief', 'Jonges, Marcel', 'Pas, Suzan D.', 'van der Eijk, Annemiek A.', 'Dirksen, Kees', 'Jansen, Casper', 'Gelinck, Luc B.S.', 'Leyten, Eliane M.S.', 'Thurkow, Ingrid', 'Groeneveld, Paul H.P.', 'van Gageldonk-Lafeber, Arianne B.', 'Koopmans, Marion P.', 'Timen, Aura', None]",Emerg Infect Dis,,,True
57c6bdd6d7150e2291c899c59152ba816372f265,PMC,"Follow-up of Contacts of Middle East Respiratory Syndrome Coronavirus–Infected Returning Travelers, the Netherlands, 2014",http://dx.doi.org/10.3201/eid2109.150560,PMC4550153,26291986,NO-CC CODE,Notification of 2 imported cases of infection with Middle East respiratory syndrome coronavirus in the Netherlands triggered comprehensive monitoring of contacts. Observed low rates of virus transmission and the psychological effect of contact monitoring indicate that thoughtful assessment of close contacts is prudent and must be guided by clinical and epidemiologic risk factors.,2015 Sep,"['Mollers, Madelief', 'Jonges, Marcel', 'Pas, Suzan D.', 'van der Eijk, Annemiek A.', 'Dirksen, Kees', 'Jansen, Casper', 'Gelinck, Luc B.S.', 'Leyten, Eliane M.S.', 'Thurkow, Ingrid', 'Groeneveld, Paul H.P.', 'van Gageldonk-Lafeber, Arianne B.', 'Koopmans, Marion P.', 'Timen, Aura', None]",Emerg Infect Dis,,,True
147048173a533a2503ddabbd4aedadd921ecb82c,PMC,"Laboratory Testing for Middle East Respiratory Syndrome Coronavirus, California, USA, 2013–2014",http://dx.doi.org/10.3201/eid2109.150476,PMC4550170,26291839,NO-CC CODE,"Since Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged, the California Department of Public Health has coordinated efforts to identify possible cases in travelers to California, USA, from affected areas. During 2013–2014, the department investigated 54 travelers for MERS-CoV; none tested positive, but 32 (62%) of 52 travelers with suspected MERS-CoV had other respiratory viruses.",2015 Sep,"['Shahkarami, Mahtab', 'Yen, Cynthia', 'Glaser, Carol', 'Xia, Dongxiang', 'Watt, James', 'Wadford, Debra A.']",Emerg Infect Dis,,,True
ce964d964ab6d20bf9ba948f00f613084d10b6de,PMC,Acute Respiratory Infections in Travelers Returning from MERS-CoV–Affected Areas,http://dx.doi.org/10.3201/eid2109.150472,PMC4550174,26291541,NO-CC CODE,"We examined which respiratory pathogens were identified during screening for Middle East respiratory syndrome coronavirus in 177 symptomatic travelers returning to Ontario, Canada, from regions affected by the virus. Influenza A and B viruses (23.1%) and rhinovirus (19.8%) were the most common pathogens identified among these travelers.",2015 Sep,"['German, Matthew', 'Olsha, Romy', 'Kristjanson, Erik', 'Marchand-Austin, Alex', 'Peci, Adriana', 'Winter, Anne-Luise', 'Gubbay, Jonathan B.']",Emerg Infect Dis,,,True
6da81d5a45c958bbd505b7775741c9e7a94ca04b,PMC,Severe Measles Infection: The Spectrum of Disease in 36 Critically Ill Adult Patients,http://dx.doi.org/10.1097/MD.0b013e3182a713c2,PMC4553975,23982057,NO-CC CODE,"France has recently witnessed a nationwide outbreak of measles. Data on severe forms of measles in adults are lacking. We sought to describe the epidemiologic, clinical, treatment, and prognostic aspects of the disease in adult patients who required admission to an intensive care unit (ICU). We performed a retrospective analysis of a cohort of 36 adults admitted to a total of 64 ICUs throughout France for complications of measles from January 1, 2009, to December 31, 2011. All cases of measles were confirmed by serologic testing and/or reverse transcription polymerase chain reaction. The cohort consisted of 21 male and 15 female patients, with a median age of 29.2 years (25th–75th interquartile range [IQR], 27.2–34.2 yr) and a median Simplified Acute Physiology Score (SAPS II) of 13 (IQR, 9–18). Among the 26 patients whose measles vaccination status was documented, none had received 2 injections. One patient had developed measles during childhood. Underlying comorbid conditions included chronic respiratory disease in 9 patients, immunosuppression in 7 patients, and obesity in 3 patients, while measles affected 5 pregnant women. Respiratory complications induced by measles infection led to ICU admission in 32 cases, and measles-related neurologic complications led to ICU admission in 2 cases. Two patients were admitted due to concurrent respiratory and neurologic complications. Bacterial superinfection of measles-related airway infection was suspected in 28 patients and was documented in 8. Four cases of community-acquired pneumonia, 6 cases of ventilator-associated pneumonia, 1 case of tracheobronchitis, and 2 cases of sinusitis were microbiologically substantiated. Of 11 patients who required mechanical ventilation, 9 developed acute respiratory distress syndrome (ARDS). Among the patients with ARDS, extraalveolar air leak complications occurred in 4 cases. Five patients died, all of whom were severely immunocompromised. On follow-up, 1 patient had severe chronic respiratory failure related to lung fibrosis, and 2 patients had mild lower limb paraparesis along with bladder dysfunction, both of which were ascribable to measles-induced encephalitis and myelitis. Among the 5 pregnant patients, the course of measles infection was uneventful, albeit 1 patient underwent emergent cesarean delivery because of fetal growth restriction. Measles is a disease with protean and potentially deceptive clinical manifestations, especially in the immunocompromised patient. Measles-associated pneumonitis and its complications, and less commonly postinfectious encephalomyelitis, are the main source of morbidity and mortality. In contrast with the usually benign course of the disease in immunocompetent patients, measles occurring in immunocompromised patients gives rise to lethal complications including ARDS, with or without bacterial superinfection. Other patients potentially at high risk for severe measles are young adults and pregnant women. Measles pneumonitis may predispose to air leak disease in patients using mechanical ventilation. To date, vaccination remains the most potent tool to control measles infection.",2013 Sep 13,"['Rafat, Cédric', 'Klouche, Kada', 'Ricard, Jean-Damien', 'Messika, Jonathan', 'Roch, Antoine', 'Machado, Sonia', 'Sonneville, Romain', 'Guisset, Olivier', 'Pujol, Wilfried', 'Guérin, Claude', 'Teboul, Jean-Louis', 'Mrozek, Natacha', 'Darmon, Michaël', 'Chemouni, Frank', 'Schmidt, Matthieu', 'Mercier, Emmanuelle', 'Dreyfuss, Didier', 'Gaudry, Stéphane']",Medicine (Baltimore),,,True
3e2677a96d2f707426791f1802e64483d8ccaabb,PMC,Advancing One Health Policy and Implementation Through the Concept of One Medicine One Science,http://dx.doi.org/10.7453/gahmj.2015.053,PMC4563898,26421234,NO-CC CODE,"Numerous interspecies disease transmission events, Ebola virus being a recent and cogent example, highlight the complex interactions between human, animal, and environmental health and the importance of addressing medicine and health in a comprehensive scientific manner. The diversity of information gained from the natural, social, behavioral, and systems sciences is critical to developing and sustainably promoting integrated health approaches that can be implemented at the local, national, and international levels to meet grand challenges. The Concept of One Medicine One Science (COMOS) as outlined herein describes the interplay between scientific knowledge that underpins health and medicine and efforts toward stabilizing local systems using 2 linked case studies: the food system and emerging infectious disease. Forums such as the International Conference of One Medicine One Science (iCOMOS), where science and policy can be debated together, missing pieces identified, and science-based collaborations formed among industry, governmental, and nongovernmental policy makers and funders, is an essential step in addressing global health. The expertise of multiple disciplines and research foci to support policy development is critical to the implementation of one health and the successful achievement of global health security goals.",2015 Sep 1,"['Cardona, Carol', 'Travis, Dominic A.', 'Berger, Kavita', 'Coat, Gwenaële', 'Kennedy, Shaun', 'Steer, Clifford J.', 'Murtaugh, Michael P.', 'Sriramarao, P.']",Glob Adv Health Med,,,True
cc50f83beb4dae7f0a60291c3e1d4868d0884c5a,PMC,Development of a Rapid Detection Method for Potato virus X by Reverse Transcription Loop-Mediated Isothermal Amplification,http://dx.doi.org/10.5423/PPJ.OA.03.2015.0044,PMC4564147,26361470,NO-CC CODE,"The primary step for efficient control of viral diseases is the development of simple, rapid, and sensitive virus detection. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) has been used to detect viral RNA molecules because of its simplicity and high sensitivity for a number of viruses. RT-LAMP for the detection of Potato virus X (PVX) was developed and compared with conventional reverse transcription polymerase chain reaction (RT-PCR) to demonstrate its advantages over RT-PCR. RT-LAMP reactions were conducted with or without a set of loop primers since one out of six primers showed PVX specificity. Based on real-time monitoring, RT-LAMP detected PVX around 30 min, compared to 120 min for RT-PCR. By adding a fluorescent reagent during the reaction, the extra step of visualization by gel electrophoresis was not necessary. RT-LAMP was conducted using simple inexpensive instruments and a regular incubator to evaluate whether RNA could be amplified at a constant temperature instead of using an expensive thermal cycler. This study shows the potential of RT-LAMP for the diagnosis of viral diseases and PVX epidemiology because of its simplicity and rapidness compared to RT-PCR.",2015 Sep 30,"['Jeong, Joojin', 'Cho, Sang-Yun', 'Lee, Wang-Hyu', 'Lee, Kui-jae', 'Ju, Ho-Jong']",Plant Pathol J,,,True
1728c90977e94eb75a6997271473f663a541640b,PMC,Antibiotic Discontinuation Rates Associated with Positive Respiratory Viral Panel and Low Procalcitonin Results in Proven or Suspected Respiratory Infections,http://dx.doi.org/10.1007/s40121-015-0087-5,PMC4575297,26342921,NO-CC CODE,"INTRODUCTION: The differentiation of viral from bacterial pneumonia is important in determining whether antibiotics are appropriate for treatment of these infections. Advances in diagnostic technologies such as respiratory panels (RP) utilizing polymerase chain reactions to detect viruses and determination of procalcitonin (PCT) concentrations may aid in this differentiation. However, some studies have shown limited impact for this purpose and thus continuation of antibiotics despite results suggesting viral infection. Our objective was to characterize clinician-prescribing behavior at our institution once RP and/or PCT results were known and suggestive of a viral respiratory infection. METHODS: This retrospective analysis was based upon records of hospitalized patients in whom proven or possible respiratory infections as indicated by RP testing, respiratory bacterial culture or International Statistical Classification of Diseases and Related Health Problems 9th revision codes for acute infectious respiratory illness was documented. Patients evaluated were required to have a RP or PCT within the first 72 h of presentation. Drug orders were evaluated for discontinuation of antibiotic therapy within 48 h of a procalcitonin of <0.25 μg/mL, a positive viral RP result, or both. RESULTS: Of 4869 patients with PCT and/or RP results, 2031 were included. PCT and RP testing were obtained in 503 and 1823 patients, respectively, with 295 patients having both. Results of these tests suggested 789 patients were potential candidates for antibiotic avoidance. These included 219 with a PCT <0.25 μg/mL, 601 with a positive viral RP result, and 31 with both. Antibiotics were administered to 307 patients (39%) within the first 72 h. In these, antibiotics were discontinued within 48 h of laboratory results availability. CONCLUSION: These results suggest that positive viral RP and low PCT results are infrequently associated with discontinuation of antibiotic therapy in proven or possible respiratory infections at our institution. Direct interventions with clinicians are likely needed to correct this behavior and decrease unnecessary antibiotic use. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40121-015-0087-5) contains supplementary material, which is available to authorized users.",2015 Sep 5,"['Timbrook, Tristan', 'Maxam, Meshell', 'Bosso, John']",Infect Dis Ther,,,False
4230f45cdf439e789aa57cbb1a080823c74d7e8a,PMC,Antibiotic Discontinuation Rates Associated with Positive Respiratory Viral Panel and Low Procalcitonin Results in Proven or Suspected Respiratory Infections,http://dx.doi.org/10.1007/s40121-015-0087-5,PMC4575297,26342921,NO-CC CODE,"INTRODUCTION: The differentiation of viral from bacterial pneumonia is important in determining whether antibiotics are appropriate for treatment of these infections. Advances in diagnostic technologies such as respiratory panels (RP) utilizing polymerase chain reactions to detect viruses and determination of procalcitonin (PCT) concentrations may aid in this differentiation. However, some studies have shown limited impact for this purpose and thus continuation of antibiotics despite results suggesting viral infection. Our objective was to characterize clinician-prescribing behavior at our institution once RP and/or PCT results were known and suggestive of a viral respiratory infection. METHODS: This retrospective analysis was based upon records of hospitalized patients in whom proven or possible respiratory infections as indicated by RP testing, respiratory bacterial culture or International Statistical Classification of Diseases and Related Health Problems 9th revision codes for acute infectious respiratory illness was documented. Patients evaluated were required to have a RP or PCT within the first 72 h of presentation. Drug orders were evaluated for discontinuation of antibiotic therapy within 48 h of a procalcitonin of <0.25 μg/mL, a positive viral RP result, or both. RESULTS: Of 4869 patients with PCT and/or RP results, 2031 were included. PCT and RP testing were obtained in 503 and 1823 patients, respectively, with 295 patients having both. Results of these tests suggested 789 patients were potential candidates for antibiotic avoidance. These included 219 with a PCT <0.25 μg/mL, 601 with a positive viral RP result, and 31 with both. Antibiotics were administered to 307 patients (39%) within the first 72 h. In these, antibiotics were discontinued within 48 h of laboratory results availability. CONCLUSION: These results suggest that positive viral RP and low PCT results are infrequently associated with discontinuation of antibiotic therapy in proven or possible respiratory infections at our institution. Direct interventions with clinicians are likely needed to correct this behavior and decrease unnecessary antibiotic use. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40121-015-0087-5) contains supplementary material, which is available to authorized users.",2015 Sep 5,"['Timbrook, Tristan', 'Maxam, Meshell', 'Bosso, John']",Infect Dis Ther,,,True
41148756482815041a85c11c6b01cb832bf1de9b,PMC,What’s Past is Prologue: A Scoping Review of Recent Public Health and Global Health Informatics Literature,http://dx.doi.org/10.5210/ojphi.v7i2.5931,PMC4576440,26392846,NO-CC CODE,"Objective: To categorize and describe the public health informatics (PHI) and global health informatics (GHI) literature between 2012 and 2014. Methods: We conducted a semi-systematic review of articles published between January 2012 and September 2014 where information and communications technologies (ICT) was a primary subject of the study or a main component of the study methodology. Additional inclusion and exclusion criteria were used to filter PHI and GHI articles from the larger biomedical informatics domain. Articles were identified using MEDLINE as well as personal bibliographies from members of the American Medical Informatics Association PHI and GHI working groups. Results: A total of 85 PHI articles and 282 GHI articles were identified. While systems in PHI continue to support surveillance activities, we identified a shift towards support for prevention, environmental health, and public health care services. Furthermore, articles from the U.S. reveal a shift towards PHI applications at state and local levels. GHI articles focused on telemedicine, mHealth and eHealth applications. The development of adequate infrastructure to support ICT remains a challenge, although we identified a small but growing set of articles that measure the impact of ICT on clinical outcomes. Discussion: There is evidence of growth with respect to both implementation of information systems within the public health enterprise as well as a widening of scope within each informatics discipline. Yet the articles also illuminate the need for more primary research studies on what works and what does not as both searches yielded small numbers of primary, empirical articles. Conclusion: While the body of knowledge around PHI and GHI continues to mature, additional studies of higher quality are needed to generate the robust evidence base needed to support continued investment in ICT by governmental health agencies.",2015 Jul 1,"['Dixon, Brian E.', 'Pina, Jamie', 'Kharrazi, Hadi', 'Gharghabi, Fardad', 'Richards, Janise']",Online J Public Health Inform,,,True
0de11ee7d10c90212661c1a3822244833f2465a0,PMC,A cascade reaction network mimicking the basic functional steps of acquired immune response,http://dx.doi.org/10.1038/nchem.2325,PMC4580978,26391084,NO-CC CODE,"Biological systems use complex ‘information processing cores’ composed of molecular networks to coordinate their external environment and internal states. An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components. Here we report the step-by-step construction of a prototype mimic of the AIS which we call Adaptive Immune Response Simulator (AIRS). DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system which responds to specific molecular stimuli in vitro. We show that this network of reactions can function in a manner which is superficially similar to the most basic responses of the vertebrate acquired immune system, including reaction sequences that mimic both humoral and cellular responses. As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices.",2015 Oct 17,"['Han, Da', 'Wu, Cuichen', 'You, Mingxu', 'Zhang, Tao', 'Wan, Shuo', 'Chen, Tao', 'Qiu, Liping', 'Zheng, Zheng', 'Liang, Hao', 'Tan, Weihong']",Nat Chem,,,True
58379e16100bc077171b5ec4af4052a4559c04a3,PMC,A cascade reaction network mimicking the basic functional steps of acquired immune response,http://dx.doi.org/10.1038/nchem.2325,PMC4580978,26391084,NO-CC CODE,"Biological systems use complex ‘information processing cores’ composed of molecular networks to coordinate their external environment and internal states. An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components. Here we report the step-by-step construction of a prototype mimic of the AIS which we call Adaptive Immune Response Simulator (AIRS). DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system which responds to specific molecular stimuli in vitro. We show that this network of reactions can function in a manner which is superficially similar to the most basic responses of the vertebrate acquired immune system, including reaction sequences that mimic both humoral and cellular responses. As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices.",2015 Oct 17,"['Han, Da', 'Wu, Cuichen', 'You, Mingxu', 'Zhang, Tao', 'Wan, Shuo', 'Chen, Tao', 'Qiu, Liping', 'Zheng, Zheng', 'Liang, Hao', 'Tan, Weihong']",Nat Chem,,,True
3148f3c48df3ecc495ce6ec7caaebcaddd1340fc,PMC,"Airport Exit and Entry Screening for Ebola — August–November 10, 2014",,PMC4584540,25503920,NO-CC CODE,,2014 Dec 12,"['Brown, Clive M.', 'Aranas, Aaron E.', 'Benenson, Gabrielle A.', 'Brunette, Gary', 'Cetron, Marty', 'Chen, Tai-Ho', 'Cohen, Nicole J.', 'Diaz, Pam', 'Haber, Yonat', 'Hale, Christa R.', 'Holton, Kelly', 'Kohl, Katrin', 'Lee, Amanda W.', 'Palumbo, Gabriel J.', 'Pearson, Kate', 'Phares, Christina R.', 'Alvarado-Ramy, Francisco', 'Roohi, Shah', 'Rotz, Lisa D.', 'Tappero, Jordan', 'Washburn, Faith M.', 'Watkins, James', 'Pesik, Nicki']",MMWR Morb Mortal Wkly Rep,,,True
495aabbaf2ffb23eaebe4b3422bfdb4e2cd122da,PMC,"Update on the Epidemiology of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection, and Guidance for the Public, Clinicians, and Public Health Authorities — January 2015",,PMC4584559,25632953,NO-CC CODE,,2015 Jan 30,"['Rha, Brian', 'Rudd, Jessica', 'Feikin, Daniel', 'Watson, John', 'Curns, Aaron T.', 'Swerdlow, David L.', 'Pallansch, Mark A.', 'Gerber, Susan I.']",MMWR Morb Mortal Wkly Rep,,,True
cfd6f06653c31766de27f2b499d1557c82ba1733,PMC,"Use and Interpretation of a Rapid Respiratory Syncytial Virus Antigen Detection Test Among Infants Hospitalized in a Neonatal Intensive Care Unit — Wisconsin, March 2015",,PMC4584593,26270063,NO-CC CODE,,2015 Aug 14,"['Elbadawi, Lina I.', 'Haupt, Thomas', 'Reisdorf, Erik', 'Danz, Tonya', 'Davis, Jeffrey P.']",MMWR Morb Mortal Wkly Rep,,,True
a452e108006dbd4db3375ce517ab1b7b35425197,PMC,"Surveillance and Preparedness for Ebola Virus Disease — New York City, 2014",,PMC4584752,25321072,NO-CC CODE,,2014 Oct 17,"['Benowitz, Isaac', 'Ackelsberg, Joel', 'Balter, Sharon E.', 'Baumgartner, Jennifer C.', 'Dentinger, Catherine', 'Fine, Anne D.', 'Harper, Scott A.', 'Jones, Lucretia E.', 'Laraque, Fabienne', 'Lee, Ellen H.', 'Merizalde, Giselle', 'Quinn, Celia', 'Slavinski, Sally', 'Winters, Ann I.', 'Weiss, Don', 'Yacisin, Kari A.', 'Varma, Jay K.', 'Layton, Marcelle C.']",MMWR Morb Mortal Wkly Rep,,,True
3f05323273dcefec161e84d7e3f814e31feedb50,PMC,"Rapidly Building Global Health Security Capacity — Uganda Demonstration Project, 2013",,PMC4584897,24476978,NO-CC CODE,,2014 Jan 31,"['Borchert, Jeff N.', 'Tappero, Jordan W.', 'Downing, Robert', 'Shoemaker, Trevor', 'Behumbiize, Prosper', 'Aceng, Jane', 'Makumbi, Issa', 'Dahlke, Melissa', 'Jarrar, Bassam', 'Lozano, Briana', 'Kasozi, Sam', 'Austin, Mark', 'Phillippe, Dru', 'Watson, Ian D.', 'Evans, Tom J.', 'Stotish, Timothy', 'Dowell, Scott F.', 'Iademarco, Michael F.', 'Ransom, Raymond', 'Balajee, Arunmozhi', 'Becknell, Kristin', 'Beauvais, Denise', 'Wuhib, Tadesse']",MMWR Morb Mortal Wkly Rep,,,True
f4f7e73df95c1229f3498aad7bf9ef1ccc3180bc,PMC,"Strengthening Global Health Security Capacity — Vietnam Demonstration Project, 2013",,PMC4584898,24476979,NO-CC CODE,,2014 Jan 31,"['Phu, Tran Dac', 'Long, Vu Ngoc', 'Hien, Nguyen Tran', 'Lan, Phan Trong', 'Lowe, Wayne', 'McConnell, Michelle S.', 'Iademarco, Michael F.', 'Partridge, Jeffrey M.', 'Kile, James C.', 'Do, Trang', 'Nadol, Patrick J.', 'Bui, Hien', 'Vu, Diep', 'Bond, Kyle', 'Nelson, David B.', 'Anderson, Lauren', 'Hunt, Kenneth V.', 'Smith, Nicole', 'Giannone, Paul', 'Klena, John', 'Beauvais, Denise', 'Becknell, Kristin', 'Tappero, Jordan W.', 'Dowell, Scott F.', 'Rzeszotarski, Peter', 'Chu, May', 'Kinkade, Carl']",MMWR Morb Mortal Wkly Rep,,,True
dd601ba03cbb74182fafd2290bc100bc5569e1c3,PMC,Final 2013 Reports of Nationally Notifiable Infectious Diseases,,PMC4584913,25272402,NO-CC CODE,,2014 Aug 15,,MMWR Morb Mortal Wkly Rep,,,True
7e4571a77ec135db692d41693918b9663e6e08c3,PMC,"Updated Information on the Epidemiology of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Guidance for the Public, Clinicians, and Public Health Authorities, 2012–2013",,PMC4585538,24067584,NO-CC CODE,,2013 Sep 27,"[None, None, None, None]",MMWR Morb Mortal Wkly Rep,,,True
bd6a6cd1c453c47af156f6e42ba837207ab45c63,PMC,"Middle East Respiratory Syndrome Coronavirus Outbreak in the Republic of Korea, 2015",http://dx.doi.org/10.1016/j.phrp.2015.08.006,PMC4588443,26473095,NO-CC CODE,"OBJECTIVES: The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the Republic of Korea started from the index case who developed fever after returning from the Middle East. He infected 26 cases in Hospital C, and consecutive nosocomial transmission proceeded throughout the nation. We provide an epidemiologic description of the outbreak, as of July 2015. METHODS: Epidemiological research was performed by direct interview of the confirmed patients and reviewing medical records. We also analyzed the incubation period, serial interval, the characteristics of superspreaders, and factors associated with mortality. Full genome sequence was obtained from sputum specimens of the index patient. RESULTS: A total of 186 confirmed patients with MERS-CoV infection across 16 hospitals were identified in the Republic of Korea. Some 44.1% of the cases were patients exposed in hospitals, 32.8% were caregivers, and 13.4% were healthcare personnel. The most common presenting symptom was fever and chills. The estimated incubation period was 6.83 days and the serial interval was 12.5 days. A total of 83.2% of the transmission events were epidemiologically linked to five superspreaders, all of whom had pneumonia at presentation and contacted hundreds of people. Older age [odds ratio (OR) = 4.86, 95% confidence interval (CI) 1.90–12.45] and underlying respiratory disease (OR = 4.90, 95% CI 1.64–14.65) were significantly associated with mortality. Phylogenetic analysis showed that the MERS-CoV of the index case clustered closest with a recent virus from Riyadh, Saudi Arabia. CONCLUSION: A single imported MERS-CoV infection case imposed a huge threat to public health and safety. This highlights the importance of robust preparedness and optimal infection prevention control. The lessons learned from the current outbreak will contribute to more up-to-date guidelines and global health security.",2015 Aug 5,,Osong Public Health Res Perspect,,,False
feb25c9a9dbc1800d43c52b03616c7a4d3e2a709,PMC,Possible Role of Rickettsia felis in Acute Febrile Illness among Children in Gabon,http://dx.doi.org/10.3201/eid2110.141825,PMC4593428,26402580,NO-CC CODE,"Rickettsia felis has been reported to be a cause of fever in sub-Saharan Africa, but this association has been poorly evaluated in Gabon. We assessed the prevalence of this bacterium among children <15 years of age in 4 areas of Gabon; the locations were in urban, semiurban, and rural areas. DNA samples from 410 febrile children and 60 afebrile children were analyzed by quantitative PCR. Overall, the prevalence of R. felis among febrile and afebrile children was 10.2% (42/410 children) and 3.3% (2/60 children), respectively. Prevalence differed among febrile children living in areas that are urban (Franceville, 1.3% [1/77]), semiurban (Koulamoutou, 2.1% [3/141]), and rural (Lastourville, 11.2% [15/134]; Fougamou, 39.7% [23/58]). Furthermore, in a rural area (Fougamou), R. felis was significantly more prevalent in febrile (39.7% [23/58]) than afebrile children (5.0% [1/20]). Additional studies are needed to better understand the pathogenic role of R. felis in this part of the world.",2015 Oct,"['Mourembou, Gaël', 'Lekana-Douki, Jean Bernard', 'Mediannikov, Oleg', 'Nzondo, Sydney Maghendji', 'Kouna, Lady Charlene', 'Essone, Jean Claude Biteghe Bi', 'Fenollar, Florence', 'Raoult, Didier']",Emerg Infect Dis,,,True
82d57f25521d98a987a697acda75c05db018436a,PMC,Final 2012 Reports of Nationally Notifiable Infectious Diseases,,PMC4604800,24133698,NO-CC CODE,,2013 Aug 23,,MMWR Morb Mortal Wkly Rep,,,True
6397e80ffb931ee6f6d03c1fe85ef82aa36e1b9a,PMC,"Update: Severe Respiratory Illness Associated with a Novel Coronavirus — Worldwide, 2012–2013",,PMC4604826,23486385,NO-CC CODE,,2013 Mar 15,"[None, 'Rha, Brian']",MMWR Morb Mortal Wkly Rep,,,True
eaa32e6b91a42f8c79e06cb8ea2285295d3c1536,PMC,"Update: Severe Respiratory Illness Associated with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) — Worldwide, 2012–2013",,PMC4604848,23760190,NO-CC CODE,,2013 Jun 14,"[None, None, None, 'Gastañaduy, Paul A.']",MMWR Morb Mortal Wkly Rep,,,True
fa0c32f39abb602e0161bf738b5292e251c0c885,PMC,"Value of Pharmacy-Based Influenza Surveillance — Ontario, Canada, 2009",,PMC4604937,23698605,NO-CC CODE,,2013 May 24,"['Aramini, Jeffery J.', 'Muchaal, Pia K.', 'Pollari, Frank']",MMWR Morb Mortal Wkly Rep,,,True
7c6305da78645e761c09e007105cfc47262773ec,PMC,Update: Recommendations for Middle East Respiratory Syndrome Coronavirus (MERS-CoV),,PMC4604945,23842446,NO-CC CODE,,2013 Jul 12,,MMWR Morb Mortal Wkly Rep,,,True
29ee29dff88547e7bce5bca49ed91282811fda0c,PMC,A phospholipase linkAGE to SARS susceptibility,http://dx.doi.org/10.1084/jem.21211insight2,PMC4612097,26482140,NO-CC CODE,,2015 Oct 19,"Schoggins, John W.",J Exp Med,,,False
bafafd9f8218f31163be864df6a1a0681ad0d16c,PMC,Origin of Long-Term Storage Stability and Nitric Oxide Release Behavior of CarboSil Polymer Doped with S-Nitroso-N-acetyl-d-penicillamine,http://dx.doi.org/10.1021/acsami.5b07501,PMC4613868,26393943,NO-CC CODE,"[Image: see text] The prolonged and localized delivery of nitric oxide (NO), a potent antithrombotic and antimicrobial agent, has many potential biomedical applications. In this work, the origin of the long-term storage stability and sustained NO release mechanism of S-nitroso-N-acetyl-d-penicillamine (SNAP)-doped CarboSil 20 80A polymer, a biomedical thermoplastic silicone-polycarbonate-urethane, is explored. Long-term (22 days) localized NO release is achieved by utilizing a cross-linked silicone rubber as topcoats, which can greatly reduce the amount of SNAP, NAP, and NAP disulfide leaching from the SNAP-doped CarboSil films, as measured by LC–MS. Raman spectroscopy and powder X-ray diffraction characterization of SNAP-doped CarboSil films demonstrate that a polymer–crystal composite is formed during the solvent evaporation process when SNAP exceeds its solubility in CarboSil (ca. 3.4–4.0 wt %). Further, when exceeding this solubility threshold, SNAP exists in an orthorhombic crystal form within the bulk of the polymer. The proposed mechanism of sustained NO release in SNAP-doped CarboSil is that the solubilized SNAP in the polymer matrix decomposes and releases NO, primarily in the water-rich regions near the polymer/solution interface, and the dissolved SNAP in the bulk polymeric phase becomes unsaturated, resulting in the dissolution of crystalline SNAP within the bulk of the polymer. This is a very slow process that ultimately leads to NO release at the physiological flux levels for >3 weeks. The increased stability of SNAP within CarboSil is attributed to the intermolecular hydrogen bonds between the SNAP molecules that crystallize. This crystallization also plays a key role in maintaining RSNO stability within the CarboSil polymer for >8 months at 37 °C (88.5% remains). Further, intravascular catheters fabricated with this new material are demonstrated to significantly decrease the formation of Staphylococcus aureus biofilm (a leading cause of nosocomial bloodstream infections) (in vitro) over a 7 day period, with 5 log units reduction of viable cell count on catheter surfaces. It is also shown that the NO release catheters can greatly reduce thrombus formation on the catheter surfaces during 7 h implantation in rabbit veins, when compared to the control catheters fabricated without SNAP. These results suggest that the SNAP-doped CarboSil system is a very attractive new composite material for creating long-term NO release medical devices with increased stability and biocompatibility.",2015 Oct 14,"['Wo, Yaqi', 'Li, Zi', 'Brisbois, Elizabeth J.', 'Colletta, Alessandro', 'Wu, Jianfeng', 'Major, Terry\nC.', 'Xi, Chuanwu', 'Bartlett, Robert H.', 'Matzger, Adam J.', 'Meyerhoff, Mark E.']",ACS Appl Mater Interfaces,,,True
c289f35b5482b7a6d778503a6360704d59cbc7da,PMC,Origin of Long-Term Storage Stability and Nitric Oxide Release Behavior of CarboSil Polymer Doped with S-Nitroso-N-acetyl-d-penicillamine,http://dx.doi.org/10.1021/acsami.5b07501,PMC4613868,26393943,NO-CC CODE,"[Image: see text] The prolonged and localized delivery of nitric oxide (NO), a potent antithrombotic and antimicrobial agent, has many potential biomedical applications. In this work, the origin of the long-term storage stability and sustained NO release mechanism of S-nitroso-N-acetyl-d-penicillamine (SNAP)-doped CarboSil 20 80A polymer, a biomedical thermoplastic silicone-polycarbonate-urethane, is explored. Long-term (22 days) localized NO release is achieved by utilizing a cross-linked silicone rubber as topcoats, which can greatly reduce the amount of SNAP, NAP, and NAP disulfide leaching from the SNAP-doped CarboSil films, as measured by LC–MS. Raman spectroscopy and powder X-ray diffraction characterization of SNAP-doped CarboSil films demonstrate that a polymer–crystal composite is formed during the solvent evaporation process when SNAP exceeds its solubility in CarboSil (ca. 3.4–4.0 wt %). Further, when exceeding this solubility threshold, SNAP exists in an orthorhombic crystal form within the bulk of the polymer. The proposed mechanism of sustained NO release in SNAP-doped CarboSil is that the solubilized SNAP in the polymer matrix decomposes and releases NO, primarily in the water-rich regions near the polymer/solution interface, and the dissolved SNAP in the bulk polymeric phase becomes unsaturated, resulting in the dissolution of crystalline SNAP within the bulk of the polymer. This is a very slow process that ultimately leads to NO release at the physiological flux levels for >3 weeks. The increased stability of SNAP within CarboSil is attributed to the intermolecular hydrogen bonds between the SNAP molecules that crystallize. This crystallization also plays a key role in maintaining RSNO stability within the CarboSil polymer for >8 months at 37 °C (88.5% remains). Further, intravascular catheters fabricated with this new material are demonstrated to significantly decrease the formation of Staphylococcus aureus biofilm (a leading cause of nosocomial bloodstream infections) (in vitro) over a 7 day period, with 5 log units reduction of viable cell count on catheter surfaces. It is also shown that the NO release catheters can greatly reduce thrombus formation on the catheter surfaces during 7 h implantation in rabbit veins, when compared to the control catheters fabricated without SNAP. These results suggest that the SNAP-doped CarboSil system is a very attractive new composite material for creating long-term NO release medical devices with increased stability and biocompatibility.",2015 Oct 14,"['Wo, Yaqi', 'Li, Zi', 'Brisbois, Elizabeth J.', 'Colletta, Alessandro', 'Wu, Jianfeng', 'Major, Terry\nC.', 'Xi, Chuanwu', 'Bartlett, Robert H.', 'Matzger, Adam J.', 'Meyerhoff, Mark E.']",ACS Appl Mater Interfaces,,,True
5e25c11546305667e32023f9bdae2c5a3bc7c25c,PMC,"Association of Higher MERS-CoV Virus Load with Severe Disease and Death, Saudi Arabia, 2014",http://dx.doi.org/10.3201/eid2111.150764,PMC4622256,26488195,NO-CC CODE,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes a spectrum of illness. We evaluated whether cycle threshold (C(t)) values (which are inversely related to virus load) were associated with clinical severity in patients from Saudi Arabia whose nasopharyngeal specimens tested positive for this virus by real-time reverse transcription PCR. Among 102 patients, median C(t) of 31.0 for the upstream of the E gene target for 41 (40%) patients who died was significantly lower than the median of 33.0 for 61 survivors (p = 0.0087). In multivariable regression analyses, risk factors for death were age >60 years), underlying illness, and decreasing C(t) for each 1-point decrease in C(t)). Results were similar for a composite severe outcome (death and/or intensive care unit admission). More data are needed to determine whether modulation of virus load by therapeutic agents affects clinical outcomes.",2015 Nov,"['Feikin, Daniel R.', 'Alraddadi, Basem', 'Qutub, Mohammed', 'Shabouni, Omaima', 'Curns, Aaron', 'Oboho, Ikwo K.', 'Tomczyk, Sara M.', 'Wolff, Bernard', 'Watson, John T.', 'Madani, Tariq A.']",Emerg Infect Dis,,,True
71762af6792d1aae86e6632954a6ca0085ee86bb,PMC,"Molecular Epidemiology of Hospital Outbreak of Middle East Respiratory Syndrome, Riyadh, Saudi Arabia, 2014",http://dx.doi.org/10.3201/eid2111.150944,PMC4622263,26484549,NO-CC CODE,"We investigated an outbreak of Middle East respiratory syndrome (MERS) at King Fahad Medical City (KFMC), Riyadh, Saudi Arabia, during March 29–May 21, 2014. This outbreak involved 45 patients: 8 infected outside KFMC, 13 long-term patients at KFMC, 23 health care workers, and 1 who had an indeterminate source of infection. Sequences of full-length MERS coronavirus (MERS-CoV) from 10 patients and a partial sequence of MERS-CoV from another patient, when compared with other MERS-CoV sequences, demonstrated that this outbreak was part of a larger outbreak that affected multiple health care facilities in Riyadh and possibly arose from a single zoonotic transmission event that occurred in December 2013 (95% highest posterior density interval November 8, 2013–February 10, 2014). This finding suggested continued health care–associated transmission for 5 months. Molecular epidemiology documented multiple external introductions in a seemingly contiguous outbreak and helped support or refute transmission pathways suspected through epidemiologic investigation.",2015 Nov,"['Fagbo, Shamsudeen F.', 'Skakni, Leila', 'Chu, Daniel K.W.', 'Garbati, Musa A.', 'Joseph, Mercy', 'Peiris, Malik', 'Hakawi, Ahmed M.']",Emerg Infect Dis,,,True
f4efcd5ff6922b61877d1bc108dc4d3bc1d1302c,PMC,"Molecular Epidemiology of Hospital Outbreak of Middle East Respiratory Syndrome, Riyadh, Saudi Arabia, 2014",http://dx.doi.org/10.3201/eid2111.150944,PMC4622263,26484549,NO-CC CODE,"We investigated an outbreak of Middle East respiratory syndrome (MERS) at King Fahad Medical City (KFMC), Riyadh, Saudi Arabia, during March 29–May 21, 2014. This outbreak involved 45 patients: 8 infected outside KFMC, 13 long-term patients at KFMC, 23 health care workers, and 1 who had an indeterminate source of infection. Sequences of full-length MERS coronavirus (MERS-CoV) from 10 patients and a partial sequence of MERS-CoV from another patient, when compared with other MERS-CoV sequences, demonstrated that this outbreak was part of a larger outbreak that affected multiple health care facilities in Riyadh and possibly arose from a single zoonotic transmission event that occurred in December 2013 (95% highest posterior density interval November 8, 2013–February 10, 2014). This finding suggested continued health care–associated transmission for 5 months. Molecular epidemiology documented multiple external introductions in a seemingly contiguous outbreak and helped support or refute transmission pathways suspected through epidemiologic investigation.",2015 Nov,"['Fagbo, Shamsudeen F.', 'Skakni, Leila', 'Chu, Daniel K.W.', 'Garbati, Musa A.', 'Joseph, Mercy', 'Peiris, Malik', 'Hakawi, Ahmed M.']",Emerg Infect Dis,,,True
3b3b3bce4bd9b3e44f01dbacad3e39fa9dad7a3c,PMC,"Middle East Respiratory Syndrome in 3 Persons, South Korea, 2015",http://dx.doi.org/10.3201/eid2111.151016,PMC4622265,26488745,NO-CC CODE,"In May 2015, Middle East respiratory syndrome coronavirus infection was laboratory confirmed in South Korea. Patients were a man who had visited the Middle East, his wife, and a man who shared a hospital room with the index patient. Rapid laboratory confirmation will facilitate subsequent prevention and control for imported cases.",2015 Nov,"['Yang, Jeong-Sun', 'Park, SungHan', 'Kim, You-Jin', 'Kang, Hae Ji', 'Kim, Hak', 'Han, Young Woo', 'Lee, Han Saem', 'Kim, Dae-Won', 'Kim, A-Reum', 'Heo, Deok Rim', 'Kim, Joo Ae', 'Kim, Su Jin', 'Nam, Jeong-Gu', 'Jung, Hee-Dong', 'Cheong, Hyang-Min', 'Kim, Kisoon', 'Lee, Joo-Shil', 'Kim, Sung Soon']",Emerg Infect Dis,,,True
33cbb0a596335d751617e5ce9d8e89c2123680f7,PMC,"Mortality Risk Factors for Middle East Respiratory Syndrome Outbreak, South Korea, 2015",http://dx.doi.org/10.3201/eid2111.151231,PMC4622268,26488869,NO-CC CODE,"As of July 15, 2015, the South Korean Ministry of Health and Welfare had reported 186 case-patients with Middle East respiratory syndrome in South Korea. For 159 case-patients with known outcomes and complete case histories, we found that older age and preexisting concurrent health conditions were risk factors for death.",2015 Nov,"['Majumder, Maimuna S.', 'Kluberg, Sheryl A.', 'Mekaru, Sumiko R.', 'Brownstein, John S.']",Emerg Infect Dis,,,True
a2373788b3199f709c0686dec692ec9030a2ac0c,PMC,"Epidemiological study of influenza virus infections in young adult outpatients from Buenos Aires, Argentina",http://dx.doi.org/10.1111/j.1750-2659.2008.00048.x,PMC4634226,19453464,NO-CC CODE,"Background  Influenza virus is the most common cause of influenza‐like illness (ILI) in adults. In Argentina, studies on influenza and other respiratory viruses were performed mostly in pediatric populations. Objectives  To determine: (1) the frequency of influenza virus and other common respiratory viruses in adult outpatients with ILI, (2) whether the signs and symptoms predict viral etiology, (3) whether viral diagnosis changes clinical management or infection control measures and (4) to characterize the influenza strains circulating in the community. Population and methods  Nasal and pharyngeal swabs from adult outpatients with ILI attending the emergency room during the winter seasons of 2004 and 2005 in Argentina were evaluated by immunofluorescence and RT‐PCR. Results  Of 151 samples analyzed, 39 (26%) were influenza A positive, 5 (3·3%) influenza B positive and 4 (2·6%) respiratory syncytial virus positive by immunofluorescence. Two samples (1·3%) were human metapneumovirus positive by RT PCR. Cell culture detected six additional influenza viruses and one adenovirus positive sample. The sensitivity of immunofluorescence for influenza compared with culture was 70%. Symptoms did not predict etiology. Conclusions  In this study, 40% of the patients with ILI had a specific viral infection and 83% were influenza viruses. Viral detection was necessary to determine the etiology as signs and symptoms were not different between patients with or without viral infection. Viral diagnosis was important to implement infectious control measures. Circulating influenza strains in this study were similar to the correspondent vaccine strains selected for the Southern hemisphere.",2008 Jul 3,"['Santamaría, Cecilia', 'Urueña, Analía', 'Videla, Cristina', 'Suarez, Ariel', 'Ganduglia, Cecilia', 'Carballal, Guadalupe', 'Bonvehi, Pablo', 'Echavarría, Marcela']",Influenza Other Respir Viruses,,,True
d6186af12acb48dec863ecc4ec38450630e32807,PMC,Human coronavirus NL63 infections in infants hospitalised with acute respiratory tract infections in South Africa,http://dx.doi.org/10.1111/j.1750-2659.2008.00049.x,PMC4634228,19453465,NO-CC CODE,"Background  Human coronavirus NL63 (HCoV‐NL63) is a novel respiratory virus which is associated with respiratory tract infections in children. Objective  To determine the role of HCoV‐NL63 in infants and young children hospitalised with acute respiratory tract infections (ARI) in Cape Town, South Africa. Methods  Respiratory specimens were collected from 1055 infants and young children hospitalised with ARI in 2003–2004. Samples were screened by RT‐PCR to detect HCoV‐NL63 and human metapneumovirus (hMPV). Standard shell vial culture and immunofluoresence was used to detect the common respiratory viruses including RSV, influenza A and B viruses, parainfluenza viruses 1, 2, 3, adenovirus and CMV. Results  A respiratory virus was found in 401/1055 (38·0%) samples. HCoV‐NL63 was detected in 9/1055 (0·85%) with peak activity during autumn (67%). Most patients had a diagnosis of pneumonia or lower respiratory tract infection (6/9; 67%). Conclusions  This is the first report of HCoV‐NL63 infections in hospitalised children in Africa. During the 2‐year period HCoV‐NL63 played a minor role in ARI in children.",2008 Jul 24,"Smuts, Heidi",Influenza Other Respir Viruses,,,True
0b94596064704e2646533ca450403c1ee7ce4ef2,PMC,Evidence of transmission and risk factors for influenza A virus in household dogs and their owners,http://dx.doi.org/10.1111/irv.12162,PMC4634238,24034782,NO-CC CODE,"BACKGROUND: The possible transmission of influenza A virus between dogs and humans is important, as in Mexico City there are approximately 1·2 million dogs. We present the first evidence of influenza A virus infection in household dogs in Mexico. OBJECTIVES: The objective of this study was to identify the presence of antibodies against influenza A virus in dogs and their owners, as well as the presence of RNA of influenza A virus in nasal exudates of dogs and, thereby, assess the possible transmission of the virus between humans and dogs. METHODS: Serum samples from household dogs and their owners were analyzed to detect the presence of antibodies against three subtypes of human influenza virus (H1N1pdm09, H1N1, and H3N2), as well as subtype H3N8 of equine influenza. We analyzed dog nasal exudates to detect influenza viral RNA. The relationship between the seropositivity of dogs and various factors (age, sex, constantly at home, and seropositivity of owners) was statistically analyzed. RESULTS: Seroprevalence for human influenza in dogs was 0·9% (1 of 113), and it was 4% (5 of 113) for equine influenza. In humans, seroprevalence was 22% for subtype H1N1pdm09, 20% for subtype H1N1, and 11% for subtype H3N2. No significant association (P > 0·05) was found between seropositivity and any of the assessed factors. Furthermore, no viral RNA was detected in the nasal exudate samples. CONCLUSIONS: Results revealed seroprevalence of the influenza virus in household dogs in Mexico City. It can be assumed that dogs are currently becoming infected with different subtypes of influenza viruses.",2013 Nov 30,"['Ramírez‐Martínez, Luis A.', 'Contreras‐Luna, María', 'De la Luz, Jazmín', 'Manjarrez, María E.', 'Rosete, Dora P.', 'Rivera‐Benitez, José F.', 'Saavedra‐Montañez, Manuel', 'Ramírez‐Mendoza, Humberto']",Influenza Other Respir Viruses,,,True
4305e4ee478f16759146ed5ae853e0ea5b017cdb,PMC,Amaryllidaceae alkaloids inhibit nuclear‐to‐cytoplasmic export of ribonucleoprotein (RNP) complex of highly pathogenic avian influenza virus H5N1,http://dx.doi.org/10.1111/irv.12035,PMC4634243,23136954,NO-CC CODE,"Please cite this paper as: He et al. (2013) Amaryllidaceae alkaloids inhibit nuclear‐to‐cytoplasmic export of ribonucleoprotein (RNP) complex of highly pathogenic avian influenza virus H5N1. Influenza and Other Respiratory Viruses 7(6), 922–931. Background  Few drugs are currently licensed to treat influenza A infection, and new therapies are needed, especially for highly pathogenic strains. Traditional medicinal plants, such as Lycoris radiata, are a potential source of new antiviral agents. Objective  To test 15 Amaryllidaceae alkaloids isolated from the bulbs of L. radiata in vitro for antiviral activities against influenza virus type A, A/Chicken/GuangDong/178/2004 (H5N1, 178). Methods  Antiviral activities of the compounds were tested in time‐of‐addition assays, hemagglutination inhibition (HI) assays, neuraminidase (NA) activity assays, and viral entry inhibition assays using H5N1‐HIV pseudoviruses. Effects of the compounds on localization and activity of the viral ribonucleoprotein (RNP) were determined by immunofluorescence and an RNP minigenome assay, respectively. Results  Among the alkaloids, lycorine (AA1), hippeastrine (AA2), hemanthamine (AA3) and 11‐hydroxy vittatine (AA4) exhibited antiviral activities, with EC(90) values of 0·52, 82·07, 4·15, and 13·45 μm, respectively. These compounds did not affect the function of the outer membrane proteins or the viral entry process and viral RNP activity. As AA1 and AA3 exhibited stronger antiviral activities, they were further analyzed. Intracellular nucleoprotein (NP) localization showed that AA1 and AA3 inhibited the RNP complex in the nucleus at an early stage of a single‐round and multi‐round of replication. Conclusion  Four Amaryllidaceae alkaloids were first determined that could exert anti‐influenza activities after virus entry into cells. Furthermore, AA1 and AA3 could inhibit nuclear‐to‐cytoplasmic export of the RNP complex of virus replication. Thus, these compounds may be developed further as anti‐influenza drug candidates.",2013 Nov 8,"['He, Jun', 'Qi, Wen‐Bao', 'Wang, Lei', 'Tian, Jin', 'Jiao, Pei‐Rong', 'Liu, Guo‐Qian', 'Ye, Wen‐Cai', 'Liao, Ming']",Influenza Other Respir Viruses,,,True
e00be029fff23d2dd375aa4f86cef9d79b1ac7c6,PMC,"Comparing the use of, and considering the need for, lumbar puncture in children with influenza or other respiratory virus infections",http://dx.doi.org/10.1111/irv.12039,PMC4634251,23122417,NO-CC CODE,"Please cite this paper as: Khandaker et al. (2012) Comparing the use of, and considering the need for, lumbar puncture in children with influenza or other respiratory virus infections. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12039. Background  The clinical presentation of influenza in infancy may be similar to serious bacterial infection and be investigated with invasive procedures like lumbar puncture (LP), despite very limited evidence that influenza occurs concomitantly with bacterial meningitis, perhaps because the diagnosis of influenza is very often not established when the decision to perform LP is being considered. Methods  A retrospective medical record review was undertaken in all children presenting to the Children’s Hospital at Westmead, Sydney, Australia, in one winter season with laboratory‐confirmed influenza or other respiratory virus infections (ORVIs) but excluding respiratory syncytial virus, to compare the use of, and reflect on the need for, the performance of invasive diagnostic procedures, principally LP, but also blood culture, in influenza and non‐influenza cases. We also determined the rate of concomitant bacterial meningitis or bacteraemia. Findings  Of 294 children, 51% had laboratory‐confirmed influenza and 49% had ORVIs such as parainfluenza viruses (34%) and adenoviruses (15%). Of those with influenza, 18% had a LP and 71% had a blood culture performed compared with 6·3% and 55·5% in the ORVI group (for both P < 0·01). In multivariate analysis, diagnosis of influenza was a strong independent predictor of both LP (P = 0·02) and blood culture (P = 0·05) being performed, and, in comparison with ORVIs, influenza cases were almost three times more likely to have a LP performed on presentation to hospital. One child with influenza (0·9%) had bacteraemia and none had meningitis. Interpretation  Children with influenza were more likely to undergo LP on presentation to hospital compared with those presenting with ORVIs. If influenza is confirmed on admission by near‐patient testing, clinicians may be reassured and less inclined to perform LP, although if meningitis is clinically suspected, the clinician should act accordingly. We found that the risk of bacterial meningitis and bacteraemia was very low in hospitalised children with influenza and ORVIs. A systematic review should be performed to investigate this across a large number of settings.",2013 Nov 5,"['Khandaker, Gulam', 'Heron, Leon', 'Rashid, Harunor', 'Li‐Kim‐Moy, Jean', 'Lester‐Smith, David', 'Kesson, Alison', 'McCaskill, Mary', 'Jones, Cheryl', 'Zurynski, Yvonne', 'Elliott, Elizabeth J.', 'Dwyer, Dominic E.', 'Booy, Robert']",Influenza Other Respir Viruses,,,True
b3fd1c9139c31dc46f7b65873260adcb21f47192,PMC,Estimates and determinants of economic impacts from influenza‐like illnesses caused by respiratory viruses in Australian children attending childcare: a cohort study,http://dx.doi.org/10.1111/irv.12138,PMC4634260,23829670,NO-CC CODE,"BACKGROUND: Influenza and other respiratory infections cause excess winter morbidity in children. This study assessed the economic impact of influenza‐like illness (ILI) on families with children attending childcare using a societal perspective. METHODS: We conducted a prospective cohort study in 90 childcare centres and one general practitioner clinics in Sydney, Australia, during 2010. Healthy children aged ≥6 months to <3 years were enrolled. Economic impacts of ILI (temperature ≥37·8°C or parental report of fever, plus ≥1 respiratory symptoms) were collected at 2 and 4 weeks after ILI onset by telephone interview. Parent‐collected respiratory specimens were tested for respiratory viruses using real‐time PCR (RT‐PCR). Costs associated with healthcare visits, medication usage, carer time lost (work or recreation) and home care and/or additional childcare were collected. Influenza‐like illness costs were described and further analysed using a Tobit model. Zero‐inflated Poisson regression was employed to compare the numbers of healthcare visits for each ILI. RESULTS: Of 381 children enrolled and analysed, 105 developed 124 ILIs. Specimens were available for 117 ILIs: five were positive by RT‐PCR for A(H1N1)pdm09, 39 for adenovirus, 39 for rhinovirus, 15 for a coronavirus and 27 for a polyomavirus. The mean cost of all ILIs was AU$626 (95% confidence interval: AU$484–768) per ILI with no significant differences observed between viruses. Carers lost on average 13 hours of work and 3 hours of leisure time per ILI. Independent drivers of ILI costs were having both parents in employed work and longer duration of ILI. In multivariate analyses, four variables were significantly associated with an increased number of healthcare visits per ILI: non‐Caucasian child, living in a detached house, both parents in employed work and having an ILI with one or more viruses identified. CONCLUSIONS: For families with a child attending childcare, ILIs cause a substantial economic burden. An ILI in a child with working parents and/or with longer duration appears to cost more in monetary terms. Healthcare visits were increased if the child was non‐Caucasian, lived in a detached house, had working parents or had a virus‐positive ILI. Our findings on the estimates and determinants of economic impacts from respiratory virus infection highlight the importance and feasibility of an interdisciplinary (epidemiology/health economics) approach to such research.",2013 Nov 6,"['Yin, Jiehui Kevin', 'Salkeld, Glenn', 'Lambert, Stephen B.', 'Dierig, Alexa', 'Heron, Leon', 'Leask, Julie', 'Yui Kwan Chow, Maria', 'Booy, Robert']",Influenza Other Respir Viruses,,,True
06d7c3e1e46a199332798bd18e31d49787b39f99,PMC,"The impact of influenza and respiratory syncytial virus on hospitalizations for lower respiratory tract infections in young children: Slovenia, 2006–2011",http://dx.doi.org/10.1111/irv.12134,PMC4634267,23782430,NO-CC CODE,"BACKGROUND: Influenza and respiratory syncytial viruses (RSV) are important viral pathogens in childhood. OBJECTIVES: Our aim was to estimate the effect of influenza and RSV on excess hospitalizations for acute lower respiratory tract infections (ALRTI) in children aged ≤5. METHODS: Retrospective, population‐based study was performed for five seasons (2006–2011). Slovenian national hospital discharge data and surveillance data were used to estimate the effect of influenza and/or RSV on ALRTI hospitalizations (acute bronchiolitis, pneumonia, and acute bronchitis) using rate difference method. RESULTS: An excess was observed in average weekly ALRTI hospitalizations per 100 000 among children aged ≤5 in all five seasons during influenza and/or RSV active period. During three seasons, there was higher excess in ALRTI hospitalizations in the period when influenza/RSV cocirculated compared with the RSV period. In pandemic season (2009/2010), the only one without influenza/RSV overlap, excess hospitalization was higher in RSV period. The highest excess of hospitalizations was found among the youngest children (0‐5 months old). In all five seasons, acute bronchiolitis was the most common ALRTI recorded in hospitalized young children. CONCLUSIONS: Respiratory syncytial viruses was leading viral pathogen associated with ALRTI hospitalizations in children aged ≤5. The cocirculation of influenza virus increased the burden of ALRTI hospitalizations especially in seasons with A(H3) predominance.",2013 Nov 20,"['Učakar, Veronika', 'Sočan, Maja', 'Trilar, Katarina Prosenc']",Influenza Other Respir Viruses,,,True
608318d1cbddf1a10ea1d6faca8b4cacf8467c29,PMC,Respiratory virus infections in hospitalized children and adults in Lao PDR,http://dx.doi.org/10.1111/irv.12135,PMC4634274,23796419,NO-CC CODE,"BACKGROUND: Acute respiratory infections are an important cause of morbidity and mortality worldwide, with a major burden of disease in developing countries. The relative contribution of viruses in acute lower respiratory infections (ALRI) is, however, poorly documented in Lao PDR. OBJECTIVE: The objective of this study is to investigate the etiology of ALRI in patients of all ages in two hospitals of Laos. METHODS: Multiplex PCR/RT‐PCR methods were used to target 18 major common respiratory viruses. Between August 2009 and October 2010, samples from 292 patients presenting with ALRI were collected. RESULTS AND CONCLUSION: Viruses were detected in 162 (55%) samples. In 48% (140/292) of the total ALRI cases, a single virus was detected while coinfections were observed in 8% (22/292) of the samples. The most frequent viruses were rhinovirus/enterovirus (35%), human respiratory syncytial virus (26%), and influenza viruses (13%). Parainfluenza viruses were detected in 9%, adenovirus in 6%, human metapneumovirus in 4%, coronaviruses (229E, NL63, OC43, HKU1) in 4%, and bocavirus in 3% of ALRI specimens. Most viral infections occurred in patients below 5 years of age. The distribution of viruses varied according to age‐groups. No significant correlation was observed between the severity of the disease and the age of patients or the virus species. This study provides the description of viral etiology among patients presenting with ALRI in Lao PDR. Additional investigations are required to better understand the clinical role of the different viruses and their seasonality in Laos.",2013 Nov 25,"['Sentilhes, Anne‐Charlotte', 'Choumlivong, Khamla', 'Celhay, Olivier', 'Sisouk, Thongchanh', 'Phonekeo, Darouny', 'Vongphrachanh, Phengta', 'Brey, Paul', 'Buchy, Philippe']",Influenza Other Respir Viruses,,,True
3b5290a5bd5c9ac633320eed77f1a7929d72b749,PMC,Epidemiological and clinical features of human coronavirus infections among different subsets of patients,http://dx.doi.org/10.1111/irv.12101,PMC4634278,23462106,NO-CC CODE,"BACKGROUND: Epidemiological and clinical data of human coronaviruses (HCoVs) infections are restricted to span 1–3 years at most. We conducted a comprehensive 9‐year study on HCoVs by analyzing 1137 respiratory samples from four subsets of patients (asymptomatic, general community, with comorbidities, and hospitalized) in São Paulo, Brazil. METHODS: A pan‐coronavirus RT‐PCR screening assay was performed, followed by species‐specific real‐time RT‐PCR monoplex assays. RESULTS: Human coronaviruses were detected in 88 of 1137 (7.7%) of the samples. The most frequently detected HCoV species were NL63 (50.0%) and OC43 (27.3%). Patients with comorbidities presented the highest risk of acquiring coronavirus infection (odds ratio = 4.17; 95% confidence interval = 1.9–9.3), and children with heart diseases revealed a significant HCoV infection presence. Dyspnea was more associated with HCoV‐229E infections (66.6%), and cyanosis was reported only in HCoV‐OC43 infections. There were interseasonal differences in the detection frequencies, with HCoV‐229E being predominant in the year 2004 (61.5%) and HCoV‐NL63 (70.8%) in 2008. CONCLUSIONS: Our data provide a novel insight into the epidemiology and clinical knowledge of HCoVs among different subsets of patients, revealing that these viruses may cause more than mild respiratory tract disease.",2013 Nov 5,"['Cabeça, Tatiane K.', 'Granato, Celso', 'Bellei, Nancy']",Influenza Other Respir Viruses,,,True
6a558dabdd9c594f052ef2cc70f1b5202bad5203,PMC,Characteristics of respiratory viral infections during influenza season in Canadian Hutterite Communities,http://dx.doi.org/10.1111/irv.12021,PMC4634280,23078120,NO-CC CODE,"Please cite this paper as: Kim et al. (2012) Characteristics of respiratory viral infections during influenza season in Canadian Hutterite Communities. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12021. Objectives:  To determined the pathogen‐specific incidence of respiratory virus infection in Hutterite communities occurring over the 2008–2009 influenza season and assess temporal characteristics of respiratory illness related to infection. Methods:  3273 participants community members enrolled in a cluster randomized trial of influenza vaccine were studied. Results:  One hundred forty‐nine participants had laboratory‐confirmed influenza, and 595 had at least one episode of laboratory‐confirmed respiratory viral infection other than influenza. Entero/rhinovirus had the highest incidence among children <5 years. Conclusions:  A decline in the incidence of infections with age was observed for influenza as well as for most other respiratory viruses.",2013 Nov 19,"['Kim, Tae H.', 'Russell, Margaret L.', 'Fonseca, Kevin', 'Aoki, Fred', 'Horsman, Gregory', 'Van Caeseele, Paul', 'Chokani, Khami', 'Voight, Mark', 'Babiuk, Lorne', 'Moss, Lorraine', 'Webby, Richard', 'Earn, David J. D.', 'Singh, Pardeep', 'Howse, Cassandra', 'Loeb, Mark']",Influenza Other Respir Viruses,,,True
05fbc9a48ec571d9292767d0ac0e54d318a6eadc,PMC,Bat cells from Pteropus alecto are susceptible to influenza A virus infection and reassortment,http://dx.doi.org/10.1111/irv.12128,PMC4634287,23710888,NO-CC CODE,"Waterfowl are primary hosts for influenza A viruses (IAVs); however, there is sporadic infection of swine and other species that pose a risk of zoonotic spread. Yellow‐shouldered bats were shown to be hosts of an IAV, thereby constituting a potential novel reservoir. We show that Pteropus alecto kidney cells (PaKi) are susceptible to infection and sustain replication of A/WSN/33 (H1N1) and A/Vietnam/1203/04 (H5N1). Importantly, we show that co‐infection of PaKi cells results in novel reassortants.",2013 Nov 27,"['Dlugolenski, Daniel', 'Jones, Les', 'Tompkins, S. Mark', 'Crameri, Gary', 'Wang, Lin‐Fa', 'Tripp, Ralph A.']",Influenza Other Respir Viruses,,,True
d12482c6be35334fcb33c74a2f0740b230d8c32e,PMC,Prior infection of pigs with a recent human H3N2 influenza virus confers minimal cross‐protection against a European swine H3N2 virus,http://dx.doi.org/10.1111/irv.12105,PMC4634290,23551882,NO-CC CODE,"BACKGROUND: H3N2 influenza viruses circulating in humans and European pigs originate from the pandemic A/Hong Kong/68 virus. Because of slower antigenic drift in swine, the antigenic divergence between swine and human viruses has been increasing. It remains unknown to what extent this results in a reduced cross‐protection between recent human and swine H3N2 influenza viruses. OBJECTIVES: We examined whether prior infection of pigs with an old [A/Victoria/3/75 (A/Vic/75)] or a more recent [A/Wisconsin/67/05 (A/Wis/05)] human H3N2 virus protected against a European swine H3N2 virus [sw/Gent/172/08 (sw/Gent/08)]. Genetic and antigenic relationships between sw/Gent/08 and a selection of human H3N2 viruses were also assessed. RESULTS: After challenge with sw/Gent/08, all challenge controls had high virus titers in the entire respiratory tract at 3 days post‐challenge and nasal virus excretion for 5–6 days. Prior infection with sw/Gent/08 or A/Vic/75 offered complete virological protection against challenge. Pigs previously inoculated with A/Wis/05 showed similar virus titers in the respiratory tract as challenge controls, but the mean duration of nasal shedding was 1·3 days shorter. Unlike sw/Gent/08‐ and A/Vic/75‐inoculated pigs, A/Wis/05‐inoculated pigs lacked cross‐reactive neutralizing antibodies against sw/Gent/08 before challenge, but they showed a more rapid antibody response to sw/Gent/08 than challenge controls after challenge. Cross‐protection and serological responses correlated with genetic and antigenic differences. CONCLUSIONS: Infection immunity to a recent human H3N2 virus confers minimal cross‐protection against a European swine H3N2 virus. We discuss our findings with regard to the recent zoonotic infections of humans in the United States with a swine‐origin H3N2 variant virus.",2013 Nov 29,"['Qiu, Yu', 'van der Meulen, Karen', 'Van Reeth, Kristien']",Influenza Other Respir Viruses,,,True
fd8fe2d13c545800ba5aa3b59356002d35f81027,PMC,Worldwide transmission and seasonal variation of pandemic influenza A(H1N1)2009 virus activity during the 2009–2010 pandemic,http://dx.doi.org/10.1111/irv.12106,PMC4634296,23551904,NO-CC CODE,"BACKGROUND: Seasonal influenza activity varies with geography and time of year. OBJECTIVE: To describe how pandemic influenza A(H1N1)2009 [A(H1N1)pdm09] activity varied during the 2009–2010 pandemic. METHODS: We analyzed influenza virological data compiled by the World Health Organization from June 2009–August 2010. We calculated weekly proportions of A(H1N1)pdm09‐positive specimens out of all A(H1N1)pdm09‐positive specimens detected during the study period for each country. We compared parameters of pandemic activity (e.g., peak A[H1N1]pdm09 weekly proportion [peak activity], number of weeks between the 5th and 95th percentiles of A(H1N1)pdm09 cumulative weekly proportion [duration of activity]) between countries in temperate and tropical–subtropical regions. We quantified the proportion of A(H1N1)pdm09 out of all influenza A specimens by country and correlated it with countries' central latitudes. RESULTS: We analyzed data from 80 countries (47 temperate, 33 tropical–subtropical). The median proportion of cases identified during the peak week was higher in temperate (0·12) than in tropical–subtropical (0·09) regions (P < 0·01). The median duration of activity was longer in tropical–subtropical (27 weeks) than in temperate countries (20 weeks) (P < 0·01). In most temperate countries (98%), peak pandemic activity occurred during the fall–winter period. There was a positive correlation between country central latitude and proportion of A(H1N1)pdm09 out of all influenza A specimens (r: 0·76; P < 0·01). CONCLUSIONS: The transmission of A(H1N1)pdm09 exhibited similarities with seasonal influenza transmission in that activity varied between temperate and tropical–subtropical countries and by time of year. Our findings suggest the potential utility of accounting for these factors during future pandemic planning.",2013 Nov 30,"['Storms, Aaron D.', 'Van Kerkhove, Maria D.', 'Azziz‐Baumgartner, Eduardo', 'Lee, Wing‐Kei', 'Widdowson, Marc‐Alain', 'Ferguson, Neil M.', 'Mounts, Anthony W.']",Influenza Other Respir Viruses,,,True
6293160da51ace8a72b0297d94e05ec9ad4276b6,PMC,Managing public health crises: the role of models in pandemic preparedness,http://dx.doi.org/10.1111/j.1750-2659.2009.00081.x,PMC4634525,19496845,NO-CC CODE,"Background  Given the enormity of challenges involved in pandemic preparedness, design and implementation of effective and cost‐effective public health policies is a major task that requires an integrated approach through engagement of scientific, administrative, and political communities across disciplines. There is ample evidence to suggest that modeling may be a viable approach to accomplish this task. Methods  To demonstrate the importance of synergism between modelers, public health experts, and policymakers, the University of Winnipeg organized an interdisciplinary workshop on the role of models in pandemic preparedness in September 2008. The workshop provided an excellent opportunity to present outcomes of recent scientific investigations that thoroughly evaluate the merits of preventive, therapeutic, and social distancing mechanisms, where community structures, priority groups, healthcare providers, and responders to emergency situations are given specific consideration. Results  This interactive workshop was clearly successful in strengthening ties between various disciplines and creating venues for modelers to effectively communicate with policymakers. The importance of modeling in pandemic planning was highlighted, and key parameters that affect policy decision‐making were identified. Core assumptions and important activities in Canadian pandemic plans at the provincial and national levels were also discussed. Conclusions  There will be little time for thoughtful and rapid reflection once an influenza pandemic strikes, and therefore preparedness is an unavoidable priority. Modeling and simulations are key resources in pandemic planning to map out interdependencies and support complex decision‐making. Models are most effective in formulating strategies for managing public health crises when there are synergies between modelers, planners, and policymakers.",2009 Mar 2,"['Moghadas, Seyed M.', 'Pizzi, Nick J.', 'Wu, Jianhong', 'Yan, Ping']",Influenza Other Respir Viruses,,,True
6d3a152b0d6066f6575684cce29eab1a7ed84b5a,PMC,Model answers or trivial pursuits? The role of mathematical models in influenza pandemic preparedness planning,http://dx.doi.org/10.1111/j.1750-2659.2007.00008.x,PMC4634556,19432634,NO-CC CODE,"The panzootic of H5N1 influenza in birds has raised concerns that the virus will mutate to spread more readily in people, leading to a human pandemic. Mathematical models have been used to interpret past pandemics and outbreaks, and to thus model possible future pandemic scenarios and interventions. We review historical influenza outbreak and transmission data, and discuss the way in which modellers have used such sources to inform model structure and assumptions. We suggest that urban attack rates in the 1918–1919 pandemic were constrained by prior immunity, that R (0) for influenza is higher than often assumed, and that control of any future pandemic could be difficult in the absence of significant prior immunity. In future, modelling assumptions, parameter estimates and conclusions should be tested against as many relevant data sets as possible. To this end, we encourage researchers to access FluWeb, an on‐line influenza database of historical pandemics and outbreaks.",2007 Mar 25,"['McVernon, J', 'McCaw, CT', 'Mathews, JD']",Influenza Other Respir Viruses,,,True
96cd30cbd4f3cecd2d0add83df270e1ae68670b1,PMC,Original Article: Real time reverse transcription (RRT)‐polymerase chain reaction (PCR) methods for detection of pandemic (H1N1) 2009 influenza virus and European swine influenza A virus infections in pigs,http://dx.doi.org/10.1111/j.1750-2659.2010.00149.x,PMC4634650,20716157,NO-CC CODE,"Please cite this paper as: Slomka et al. (2010) Real time reverse transcription (RRT)‐polymerase chain reaction (PCR) methods for detection of pandemic (H1N1) 2009 influenza virus and European swine influenza A virus infections in pigs. Influenza and Other Respiratory Viruses 4(5), 277–293. Background  There is a requirement to detect and differentiate pandemic (H1N1) 2009 (H1N1v) and established swine influenza A viruses (SIVs) by real time reverse transcription (RRT) PCR methods. Objectives  First, modify an existing matrix (M) gene RRT PCR for sensitive generic detection of H1N1v and other European SIVs. Second, design an H1 RRT PCR to specifically detect H1N1v infections. Methods  RRT PCR assays were used to test laboratory isolates of SIV (n = 51; 37 European and 14 North American), H1N1v (n = 5) and avian influenza virus (AIV; n = 43). Diagnostic sensitivity and specificity were calculated for swabs (n = 133) and tissues (n = 116) collected from field cases and pigs infected experimentally with SIVs and H1N1v. Results  The “perfect match” M gene RRT PCR was the most sensitive variant of this test for detection of established European SIVs and H1N1v. H1 RRT PCR specifically detected H1N1v but not European SIVs. Validation with clinical specimens included comparison with virus isolation (VI) as a “gold standard”, while field infection with H1N1v in swine was independently confirmed by sequencing H1N1v amplified by conventional RT PCR. “Perfect match” M gene RRT PCR had 100% sensitivity and 95·2% specificity for swabs, 93·6% and 98·6% for tissues. H1 RRT PCR demonstrated sensitivity and specificity of 100% and 99·1%, respectively, for the swabs, and 100% and 100% for the tissues. Conclusions  Two RRT PCRs for the purposes of (i) generic detection of SIV and H1N1v infection in European pigs, and for (ii) specific detection of H1N1v (pandemic influenza) infection were validated.",2010 Sep 17,"['Slomka, Marek J.', 'Densham, Anstice L. E.', 'Coward, Vivien J.', 'Essen, Steve', 'Brookes, Sharon M.', 'Irvine, Richard M.', 'Spackman, Erica', 'Ridgeon, Jonathan', 'Gardner, Rebecca', 'Hanna, Amanda', 'Suarez, David L.', 'Brown, Ian H.']",Influenza Other Respir Viruses,,,True
c9033f4f43cc3b136aa09c5ade7f547fdbac351a,PMC,Introductory Editorial,http://dx.doi.org/10.1111/j.1750-2659.2006.00002.x,PMC4634660,19453475,NO-CC CODE,,2007 Jan 19,"Hampson, Alan W.",Influenza Other Respir Viruses,,,False
ddfb32b38e497cd4ff03d23270f3b7d4539df348,PMC,International Society for Influenza and other Respiratory Viruses and the new journal,http://dx.doi.org/10.1111/j.1750-2659.2006.00001.x,PMC4634663,19453474,NO-CC CODE,,2007 Jan 19,"Schild, Geoffrey C.",Influenza Other Respir Viruses,,,False
49426592699cbc14f6c757e989d956c240fdabc5,PMC,Acute respiratory infection and bacteraemia as causes of non-malarial febrile illness in African children: a narrative review,http://dx.doi.org/10.15172/pneu.2015.6/488,PMC4650196,26594615,NO-CC CODE,"The replacement of “presumptive treatment for malaria” by “test before treat” strategies for the management of febrile illness is raising awareness of the importance of knowing more about the causes of illness in children who are suspected to have malaria but return a negative parasitological test. The most common cause of non-malarial febrile illness (NMFI) in African children is respiratory tract inflection. Whilst the bacterial causes of NMFI are well known, the increasing use of sensitive techniques such as polymerase chain reaction (PCR) tests is revealing large numbers of viruses that are potential respiratory pathogens. However, many of these organisms are commonly present in the respiratory tract of healthy children so causality and risk factors for pneumonia remain poorly understood. Inflection with a combination of viral and bacterial pathogens is increasingly recognised as important in the pathogenesis of pneumonia. Similarly, blood stream inflections with organisms typically grown by aerobic culture are well known but a growing number of organisms that can be identified only by PCR, viral culture, or serology are now recognised to be common pathogens in African children. The high mortality of hospitalised children on the first or second day of admission suggests that, unless results are rapidly available, diagnostic tests to identify specific causes of illness will still be of limited use in guiding the potentially life saving decisions relating to initial treatment of children admitted to district hospitals in Africa with severe febrile illness and a negative test for malaria. Malaria control and the introduction of vaccines against Haemophilus influenzae type b and pneumococcal disease are contributing to improved child survival in Africa. However, increased parasitological testing for malaria is associated with increased use of antbiotics to which resistance is already high.",2015 Dec 1,"['Muro, Florid', 'Reyburn, Rita', 'Reyburn, Hugh']",Pneumonia (Nathan),,,False
cff0235863f34320b1b684ee7b3469900d0576cf,PMC,Nuclear Magnetic Resonance-Assisted Prediction of Secondary Structure for RNA: Incorporation of Direction-Dependent Chemical Shift Constraints,http://dx.doi.org/10.1021/acs.biochem.5b00833,PMC4666457,26451676,NO-CC CODE,"[Image: see text] Knowledge of RNA structure is necessary to determine structure–function relationships and to facilitate design of potential therapeutics. RNA secondary structure prediction can be improved by applying constraints from nuclear magnetic resonance (NMR) experiments to a dynamic programming algorithm. Imino proton walks from NOESY spectra reveal double-stranded regions. Chemical shifts of protons in GH1, UH3, and UH5 of GU pairs, UH3, UH5, and AH2 of AU pairs, and GH1 of GC pairs were analyzed to identify constraints for the 5′ to 3′ directionality of base pairs in helices. The 5′ to 3′ directionality constraints were incorporated into an NMR-assisted prediction of secondary structure (NAPSS-CS) program. When it was tested on 18 structures, including nine pseudoknots, the sensitivity and positive predictive value were improved relative to those of three unrestrained programs. The prediction accuracy for the pseudoknots improved the most. The program also facilitates assignment of chemical shifts to individual nucleotides, a necessary step for determining three-dimensional structure.",2015 Nov 17,"['Chen, Jonathan\nL.', 'Bellaousov, Stanislav', 'Tubbs, Jason D.', 'Kennedy, Scott D.', 'Lopez, Michael J.', 'Mathews, David H.', 'Turner, Douglas H.']",Biochemistry,,,True
b9b4213574ea78c40397f25bd72806df09c05013,PMC,Nuclear Magnetic Resonance-Assisted Prediction of Secondary Structure for RNA: Incorporation of Direction-Dependent Chemical Shift Constraints,http://dx.doi.org/10.1021/acs.biochem.5b00833,PMC4666457,26451676,NO-CC CODE,"[Image: see text] Knowledge of RNA structure is necessary to determine structure–function relationships and to facilitate design of potential therapeutics. RNA secondary structure prediction can be improved by applying constraints from nuclear magnetic resonance (NMR) experiments to a dynamic programming algorithm. Imino proton walks from NOESY spectra reveal double-stranded regions. Chemical shifts of protons in GH1, UH3, and UH5 of GU pairs, UH3, UH5, and AH2 of AU pairs, and GH1 of GC pairs were analyzed to identify constraints for the 5′ to 3′ directionality of base pairs in helices. The 5′ to 3′ directionality constraints were incorporated into an NMR-assisted prediction of secondary structure (NAPSS-CS) program. When it was tested on 18 structures, including nine pseudoknots, the sensitivity and positive predictive value were improved relative to those of three unrestrained programs. The prediction accuracy for the pseudoknots improved the most. The program also facilitates assignment of chemical shifts to individual nucleotides, a necessary step for determining three-dimensional structure.",2015 Nov 17,"['Chen, Jonathan\nL.', 'Bellaousov, Stanislav', 'Tubbs, Jason D.', 'Kennedy, Scott D.', 'Lopez, Michael J.', 'Mathews, David H.', 'Turner, Douglas H.']",Biochemistry,,,True
add01845567b1c863e734710038329e3545aa3dd,PMC,"Characteristics of Traveler with Middle East Respiratory Syndrome, China, 2015",http://dx.doi.org/10.3201/eid2112.151232,PMC4672405,26583433,NO-CC CODE,,2015 Dec,"['Da Guan, Wen', 'Mok, Chris Ka Pun', 'Chen, Zi Lin', 'Feng, Li Qiang', 'Li, Zheng Tu', 'Huang, Ji Cheng', 'Ke, Chang Wen', 'Deng, Xilong', 'Ling, Yun', 'Wu, Shi Guan', 'Niu, Xue Feng', 'Perera, Ranawaka A', 'Da Xu, Yuan', 'Zhao, Jincun', 'Zhang, Lin Qi', 'Li, Yi Min', 'Chen, Rong Chang', 'Peiris, Malik', 'Chen, Ling', 'Zhong, Nan Shan']",Emerg Infect Dis,,,True
79b9de8046987ccda00f034d86d599edb77bc32b,PMC,"Characteristics of Traveler with Middle East Respiratory Syndrome, China, 2015",http://dx.doi.org/10.3201/eid2112.151232,PMC4672405,26583433,NO-CC CODE,,2015 Dec,"['Da Guan, Wen', 'Mok, Chris Ka Pun', 'Chen, Zi Lin', 'Feng, Li Qiang', 'Li, Zheng Tu', 'Huang, Ji Cheng', 'Ke, Chang Wen', 'Deng, Xilong', 'Ling, Yun', 'Wu, Shi Guan', 'Niu, Xue Feng', 'Perera, Ranawaka A', 'Da Xu, Yuan', 'Zhao, Jincun', 'Zhang, Lin Qi', 'Li, Yi Min', 'Chen, Rong Chang', 'Peiris, Malik', 'Chen, Ling', 'Zhong, Nan Shan']",Emerg Infect Dis,,,True
ae259a3fbe7fe1269fb1fa49803adb40316e3c3e,PMC,"Isolation of Porcine Epidemic Diarrhea Virus during Outbreaks in South Korea, 2013–2014",http://dx.doi.org/10.3201/eid2112.150437,PMC4672425,26584230,NO-CC CODE,,2015 Dec,"['Chung, Hee-Chun', 'Nguyen, Van Giap', 'Moon, Hyoung-Joon', 'Lee, Jee-Hoon', 'Park, Seong-Jun', 'Lee, Ga-Eun', 'Kim, Hye-Kwon', 'Noh, You-Shun', 'Lee, Chan-Hee', 'Goede, Dane', 'Park, Bong Kyun']",Emerg Infect Dis,,,True
42f1a4559a7a54113e1d9b341cf6cb6815c0e023,PMC,"Isolation of Porcine Epidemic Diarrhea Virus during Outbreaks in South Korea, 2013–2014",http://dx.doi.org/10.3201/eid2112.150437,PMC4672425,26584230,NO-CC CODE,,2015 Dec,"['Chung, Hee-Chun', 'Nguyen, Van Giap', 'Moon, Hyoung-Joon', 'Lee, Jee-Hoon', 'Park, Seong-Jun', 'Lee, Ga-Eun', 'Kim, Hye-Kwon', 'Noh, You-Shun', 'Lee, Chan-Hee', 'Goede, Dane', 'Park, Bong Kyun']",Emerg Infect Dis,,,True
df5c297cca7c38328fdac4a3cfef5bda4e948e93,PMC,"Asymptomatic MERS-CoV Infection in Humans Possibly Linked to Infected Dromedaries Imported from Oman to United Arab Emirates, May 2015",http://dx.doi.org/10.3201/eid2112.151132,PMC4672428,26584223,NO-CC CODE,"In May 2015 in United Arab Emirates, asymptomatic Middle East respiratory syndrome coronavirus infection was identified through active case finding in 2 men with exposure to infected dromedaries. Epidemiologic and virologic findings suggested zoonotic transmission. Genetic sequences for viruses from the men and camels were similar to those for viruses recently detected in other countries.",2015 Dec,"['Al Hammadi, Zulaikha M.', 'Chu, Daniel K.W.', 'Eltahir, Yassir M.', 'Al Hosani, Farida', 'Al Mulla, Mariam', 'Tarnini, Wasim', 'Hall, Aron J.', 'Perera, Ranawaka A.P.M.', 'Abdelkhalek, Mohamed M.', 'Peiris, J.S.M.', 'Al Muhairi, Salama S.', 'Poon, Leo L.M.']",Emerg Infect Dis,,,True
f2052c2184052f6fc846cba6e9afcab029364350,PMC,"Asymptomatic MERS-CoV Infection in Humans Possibly Linked to Infected Dromedaries Imported from Oman to United Arab Emirates, May 2015",http://dx.doi.org/10.3201/eid2112.151132,PMC4672428,26584223,NO-CC CODE,"In May 2015 in United Arab Emirates, asymptomatic Middle East respiratory syndrome coronavirus infection was identified through active case finding in 2 men with exposure to infected dromedaries. Epidemiologic and virologic findings suggested zoonotic transmission. Genetic sequences for viruses from the men and camels were similar to those for viruses recently detected in other countries.",2015 Dec,"['Al Hammadi, Zulaikha M.', 'Chu, Daniel K.W.', 'Eltahir, Yassir M.', 'Al Hosani, Farida', 'Al Mulla, Mariam', 'Tarnini, Wasim', 'Hall, Aron J.', 'Perera, Ranawaka A.P.M.', 'Abdelkhalek, Mohamed M.', 'Peiris, J.S.M.', 'Al Muhairi, Salama S.', 'Poon, Leo L.M.']",Emerg Infect Dis,,,False
0c4bfbf56443b6d80e018f40564789037ce69418,PMC,Porcine Deltacoronavirus in Mainland China,http://dx.doi.org/10.3201/eid2112.150283,PMC4672429,26584185,NO-CC CODE,,2015 Dec,"['Dong, Nan', 'Fang, Liurong', 'Zeng, Songlin', 'Sun, Qianqian', 'Chen, Huanchun', 'Xiao, Shaobo']",Emerg Infect Dis,,,True
716b3356b6e9164e151a014393eaeb86d93f4311,PMC,Porcine Deltacoronavirus in Mainland China,http://dx.doi.org/10.3201/eid2112.150283,PMC4672429,26584185,NO-CC CODE,,2015 Dec,"['Dong, Nan', 'Fang, Liurong', 'Zeng, Songlin', 'Sun, Qianqian', 'Chen, Huanchun', 'Xiao, Shaobo']",Emerg Infect Dis,,,False
8edd711f742484517e3e3e206b4cb7b3441722f9,PMC,"Porcine Epidemic Diarrhea Virus among Farmed Pigs, Ukraine",http://dx.doi.org/10.3201/eid2112.150272,PMC4672447,26584081,NO-CC CODE,"An outbreak of porcine epidemic diarrhea occurred in the summer of 2014 in Ukraine, severely affecting piglets <10 days of age; the mortality rate approached 100%. Full genome sequencing showed the virus to be closely related to strains reported from North America, showing a sequence identity of up to 99.8%.",2015 Dec,"['Dastjerdi, Akbar', 'Carr, John', 'Ellis, Richard J.', 'Steinbach, Falko', 'Williamson, Susanna']",Emerg Infect Dis,,,True
32a899bfdc328494e01afe9a36452c579374e51d,PMC,"Porcine Epidemic Diarrhea Virus among Farmed Pigs, Ukraine",http://dx.doi.org/10.3201/eid2112.150272,PMC4672447,26584081,NO-CC CODE,"An outbreak of porcine epidemic diarrhea occurred in the summer of 2014 in Ukraine, severely affecting piglets <10 days of age; the mortality rate approached 100%. Full genome sequencing showed the virus to be closely related to strains reported from North America, showing a sequence identity of up to 99.8%.",2015 Dec,"['Dastjerdi, Akbar', 'Carr, John', 'Ellis, Richard J.', 'Steinbach, Falko', 'Williamson, Susanna']",Emerg Infect Dis,,,False
b3bf0cacc79b216fa4d6218521b5730e9023ac00,PMC,"No Evidence of Gouléako and Herbert Virus Infections in Pigs, Côte d’Ivoire and Ghana",http://dx.doi.org/10.3201/eid2112.141840,PMC4672453,26583956,NO-CC CODE,A recent report suggested that 2 novel bunyaviruses discovered in insects in Côte d’Ivoire caused lethal disease in swine in South Korea. We conducted cell culture studies and tested serum from pigs exposed to mosquitoes in Côte d’Ivoire and Ghana and found no evidence for infection in pigs.,2015 Dec,"['Junglen, Sandra', 'Marklewitz, Marco', 'Zirkel, Florian', 'Wollny, Robert', 'Meyer, Benjamin', 'Heidemann, Hanna', 'Metzger, Sonja', 'Annan, Augustina', 'Dei, Dickson', 'Leendertz, Fabian H.', 'Oppong, Samuel', 'Drosten, Christian']",Emerg Infect Dis,,,True
cdfa82e974f1631bc2e4afb8132180ee84bc4b5e,PMC,"No Evidence of Gouléako and Herbert Virus Infections in Pigs, Côte d’Ivoire and Ghana",http://dx.doi.org/10.3201/eid2112.141840,PMC4672453,26583956,NO-CC CODE,A recent report suggested that 2 novel bunyaviruses discovered in insects in Côte d’Ivoire caused lethal disease in swine in South Korea. We conducted cell culture studies and tested serum from pigs exposed to mosquitoes in Côte d’Ivoire and Ghana and found no evidence for infection in pigs.,2015 Dec,"['Junglen, Sandra', 'Marklewitz, Marco', 'Zirkel, Florian', 'Wollny, Robert', 'Meyer, Benjamin', 'Heidemann, Hanna', 'Metzger, Sonja', 'Annan, Augustina', 'Dei, Dickson', 'Leendertz, Fabian H.', 'Oppong, Samuel', 'Drosten, Christian']",Emerg Infect Dis,,,True
36878ef3cdf585376c19d3f19f3a50a1bd466615,PMC,"Kinetics of Serologic Responses to MERS Coronavirus Infection in Humans, South Korea",http://dx.doi.org/10.3201/eid2112.151421,PMC4672454,26583829,NO-CC CODE,"We investigated the kinetics of serologic responses to Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using virus neutralization and MERS-CoV S1 IgG ELISA tests. In most patients, robust antibody responses developed by the third week of illness. Delayed antibody responses with the neutralization test were associated with more severe disease.",2015 Dec,"['Park, Wan Beom', 'Perera, Ranawaka A.P.M.', 'Choe, Pyoeng Gyun', 'Lau, Eric H.Y.', 'Choi, Seong Jin', 'Chun, June Young', 'Oh, Hong Sang', 'Song, Kyoung-Ho', 'Bang, Ji Hwan', 'Kim, Eu Suk', 'Kim, Hong Bin', 'Park, Sang Won', 'Kim, Nam Joong', 'Man Poon, Leo Lit', 'Peiris, Malik', 'Oh, Myoung-don']",Emerg Infect Dis,,,True
b2d803efef67c2b66ffe61658d853421bdd20927,PMC,"Kinetics of Serologic Responses to MERS Coronavirus Infection in Humans, South Korea",http://dx.doi.org/10.3201/eid2112.151421,PMC4672454,26583829,NO-CC CODE,"We investigated the kinetics of serologic responses to Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using virus neutralization and MERS-CoV S1 IgG ELISA tests. In most patients, robust antibody responses developed by the third week of illness. Delayed antibody responses with the neutralization test were associated with more severe disease.",2015 Dec,"['Park, Wan Beom', 'Perera, Ranawaka A.P.M.', 'Choe, Pyoeng Gyun', 'Lau, Eric H.Y.', 'Choi, Seong Jin', 'Chun, June Young', 'Oh, Hong Sang', 'Song, Kyoung-Ho', 'Bang, Ji Hwan', 'Kim, Eu Suk', 'Kim, Hong Bin', 'Park, Sang Won', 'Kim, Nam Joong', 'Man Poon, Leo Lit', 'Peiris, Malik', 'Oh, Myoung-don']",Emerg Infect Dis,,,False
94887a1075f0c58470a7c380579cde5fac84be14,PMC,Rapid and Effective Virucidal Activity of Povidone-Iodine Products Against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and Modified Vaccinia Virus Ankara (MVA),http://dx.doi.org/10.1007/s40121-015-0091-9,PMC4675768,26416214,NO-CC CODE,"INTRODUCTION: Since the first case of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection was reported in 2012, the virus has infected more than 1300 individuals in 26 countries, and caused more than 480 deaths. Human-to-human transmission requires close contact, and has typically occurred in the healthcare setting. Improved global awareness, together with improved hygiene practices in healthcare facilities, has been highlighted as key strategies in controlling the spread of MERS-CoV. This study tested the in vitro efficacy of three formulations of povidone iodine (PVP-I: 4% PVP-I skin cleanser, 7.5% PVP-I surgical scrub, and 1% PVP-I gargle/mouthwash) against a reference virus (Modified vaccinia virus Ankara, MVA) and MERS-CoV. METHODS: According to EN14476, a standard suspension test was used to assess virucidal activity against MVA and large volume plating was used for MERS-CoV. All products were tested under clean (0.3 g/L bovine serum albumin, BSA) and dirty conditions (3.0 g/L BSA + 3.0 mL/L erythrocytes), with application times of 15, 30, and 60 s for MVA, and 15 s for MERS-CoV. The products were tested undiluted, 1:10 and 1:100 diluted against MVA, and undiluted against MERS-CoV. RESULTS: A reduction in virus titer of ≥4 log(10) (corresponding to an inactivation of ≥99.99%) was regarded as evidence of virucidal activity. This was achieved versus MVA and MERS-CoV, under both clean and dirty conditions, within 15 s of application of each undiluted PVP-I product. CONCLUSION: These data indicate that PVP-I-based hand wash products for potentially contaminated skin, and PVP-I gargle/mouthwash for reduction of viral load in the oral cavity and the oropharynx, may help to support hygiene measures to prevent transmission of MERS-CoV. FUNDING: Mundipharma Research GmbH & Co. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40121-015-0091-9) contains supplementary material, which is available to authorized users.",2015 Dec 28,"['Eggers, Maren', 'Eickmann, Markus', 'Zorn, Juergen']",Infect Dis Ther,,,False
6394756d9759bedd7e0053f7b99a7df74da7a16a,PMC,Rapid and Effective Virucidal Activity of Povidone-Iodine Products Against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and Modified Vaccinia Virus Ankara (MVA),http://dx.doi.org/10.1007/s40121-015-0091-9,PMC4675768,26416214,NO-CC CODE,"INTRODUCTION: Since the first case of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection was reported in 2012, the virus has infected more than 1300 individuals in 26 countries, and caused more than 480 deaths. Human-to-human transmission requires close contact, and has typically occurred in the healthcare setting. Improved global awareness, together with improved hygiene practices in healthcare facilities, has been highlighted as key strategies in controlling the spread of MERS-CoV. This study tested the in vitro efficacy of three formulations of povidone iodine (PVP-I: 4% PVP-I skin cleanser, 7.5% PVP-I surgical scrub, and 1% PVP-I gargle/mouthwash) against a reference virus (Modified vaccinia virus Ankara, MVA) and MERS-CoV. METHODS: According to EN14476, a standard suspension test was used to assess virucidal activity against MVA and large volume plating was used for MERS-CoV. All products were tested under clean (0.3 g/L bovine serum albumin, BSA) and dirty conditions (3.0 g/L BSA + 3.0 mL/L erythrocytes), with application times of 15, 30, and 60 s for MVA, and 15 s for MERS-CoV. The products were tested undiluted, 1:10 and 1:100 diluted against MVA, and undiluted against MERS-CoV. RESULTS: A reduction in virus titer of ≥4 log(10) (corresponding to an inactivation of ≥99.99%) was regarded as evidence of virucidal activity. This was achieved versus MVA and MERS-CoV, under both clean and dirty conditions, within 15 s of application of each undiluted PVP-I product. CONCLUSION: These data indicate that PVP-I-based hand wash products for potentially contaminated skin, and PVP-I gargle/mouthwash for reduction of viral load in the oral cavity and the oropharynx, may help to support hygiene measures to prevent transmission of MERS-CoV. FUNDING: Mundipharma Research GmbH & Co. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40121-015-0091-9) contains supplementary material, which is available to authorized users.",2015 Dec 28,"['Eggers, Maren', 'Eickmann, Markus', 'Zorn, Juergen']",Infect Dis Ther,,,True
dbb74d7f7208f09f5c107ecc18d9b28fcbc4d67a,PMC,"Phosphonooxymethyl Prodrug of Triptolide: Synthesis, Physicochemical Characterization, and Efficacy in Human Colon Adenocarcinoma and Ovarian Cancer Xenografts",http://dx.doi.org/10.1021/acs.jmedchem.5b01329,PMC4678411,26596892,NO-CC CODE,"[Image: see text] A disodium phosphonooxymethyl prodrug of the antitumor agent triptolide was prepared from the natural product in three steps (39% yield) and displayed excellent aqueous solubility at pH 7.4 (61 mg/mL) compared to the natural product (17 μg/mL). The estimated shelf life (t(90)) for hydrolysis of the prodrug at 4 °C and pH 7.4 was found to be two years. In a mouse model of human colon adenocarcinoma (HT-29), the prodrug administered intraperitoneally was effective in reducing or eliminating xenograft tumors at dose levels as low as 0.3 mg/kg when given daily and at 0.9 mg/kg when given less frequently. When given via intraperitoneal and oral routes at daily doses of 0.6 and 0.9 mg/kg, the prodrug was also effective and well tolerated in a mouse model of human ovarian cancer (A2780).",2015 Dec 10,"['Patil, Satish', 'Lis, Lev G.', 'Schumacher, Robert\nJ.', 'Norris, Beverly J.', 'Morgan, Monique L.', 'Cuellar, Rebecca A. D.', 'Blazar, Bruce R.', 'Suryanarayanan, Raj', 'Gurvich, Vadim J.', 'Georg, Gunda I.']",J Med Chem,,,True
d7e49619dea5bcfca63185a869586c0685d4a266,PMC,"Phosphonooxymethyl Prodrug of Triptolide: Synthesis, Physicochemical Characterization, and Efficacy in Human Colon Adenocarcinoma and Ovarian Cancer Xenografts",http://dx.doi.org/10.1021/acs.jmedchem.5b01329,PMC4678411,26596892,NO-CC CODE,"[Image: see text] A disodium phosphonooxymethyl prodrug of the antitumor agent triptolide was prepared from the natural product in three steps (39% yield) and displayed excellent aqueous solubility at pH 7.4 (61 mg/mL) compared to the natural product (17 μg/mL). The estimated shelf life (t(90)) for hydrolysis of the prodrug at 4 °C and pH 7.4 was found to be two years. In a mouse model of human colon adenocarcinoma (HT-29), the prodrug administered intraperitoneally was effective in reducing or eliminating xenograft tumors at dose levels as low as 0.3 mg/kg when given daily and at 0.9 mg/kg when given less frequently. When given via intraperitoneal and oral routes at daily doses of 0.6 and 0.9 mg/kg, the prodrug was also effective and well tolerated in a mouse model of human ovarian cancer (A2780).",2015 Dec 10,"['Patil, Satish', 'Lis, Lev G.', 'Schumacher, Robert\nJ.', 'Norris, Beverly J.', 'Morgan, Monique L.', 'Cuellar, Rebecca A. D.', 'Blazar, Bruce R.', 'Suryanarayanan, Raj', 'Gurvich, Vadim J.', 'Georg, Gunda I.']",J Med Chem,,,False
017ca5bdac589a37196df7b8e077c4c371ab32da,PMC,Pro/con clinical debate: Isolation precautions for all intensive care unit patients with methicillin-resistant Staphylococcus aureus colonization are essential,http://dx.doi.org/10.1186/cc2817,PMC468889,15153232,NO-CC CODE,"Antibiotic-resistant bacteria are an increasingly common problem in intensive care units (ICUs), and they are capable of impacting on patient outcome, the ICU's budget and bed availability. This issue, coupled with recent outbreaks of illnesses that pose a direct risk to ICU staff (such as SARS [severe acute respiratory syndrome]), has led to renewed emphasis on infection control measures and practitioners in the ICU. Infection control measures frequently cause clinicians to practice in a more time consuming way. As a result it is not surprising that ensuring compliance with these measures is not always easy, particularly when their benefit is not immediately obvious. In this issue of Critical Care, two experts face off over the need to isolate patients infected with methicillin-resistant Staphylococcus aureus.",2004 Feb 19,"['Farr, Barry M', 'Bellingan, Geoffrey']",Crit Care,,,True
a7413d2d2f103768cb45b13fc91c8f96568eaccb,PMC,"Synthesis, Binding and Antiviral Properties of Potent Core-Extended Naphthalene Diimides Targeting the HIV-1 Long Terminal Repeat Promoter G-Quadruplexes",http://dx.doi.org/10.1021/acs.jmedchem.5b01283,PMC4690987,26599611,NO-CC CODE,"[Image: see text] We have previously reported that stabilization of the G-quadruplex structures in the HIV-1 long terminal repeat (LTR) promoter suppresses viral transcription. Here we sought to develop new G-quadruplex ligands to be exploited as antiviral compounds by enhancing binding toward the viral G-quadruplex structures. We synthesized naphthalene diimide derivatives with a lateral expansion of the aromatic core. The new compounds were able to bind/stabilize the G-quadruplex to a high extent, and some of them displayed clear-cut selectivity toward the viral G-quadruplexes with respect to the human telomeric G-quadruplexes. This feature translated into low nanomolar anti-HIV-1 activity toward two viral strains and encouraging selectivity indexes. The selectivity depended on specific recognition of LTR loop residues; the mechanism of action was ascribed to inhibition of LTR promoter activity in cells. This is the first example of G-quadruplex ligands that show increased selectivity toward the viral G-quadruplexes and display remarkable antiviral activity.",2015 Dec 24,"['Perrone, Rosalba', 'Doria, Filippo', 'Butovskaya, Elena', 'Frasson, Ilaria', 'Botti, Silvia', 'Scalabrin, Matteo', 'Lago, Sara', 'Grande, Vincenzo', 'Nadai, Matteo', 'Freccero, Mauro', 'Richter, Sara N.']",J Med Chem,,,True
cac461b8650d4c26c02f44c3ec815f8de41595aa,PMC,"Synthesis, Binding and Antiviral Properties of Potent Core-Extended Naphthalene Diimides Targeting the HIV-1 Long Terminal Repeat Promoter G-Quadruplexes",http://dx.doi.org/10.1021/acs.jmedchem.5b01283,PMC4690987,26599611,NO-CC CODE,"[Image: see text] We have previously reported that stabilization of the G-quadruplex structures in the HIV-1 long terminal repeat (LTR) promoter suppresses viral transcription. Here we sought to develop new G-quadruplex ligands to be exploited as antiviral compounds by enhancing binding toward the viral G-quadruplex structures. We synthesized naphthalene diimide derivatives with a lateral expansion of the aromatic core. The new compounds were able to bind/stabilize the G-quadruplex to a high extent, and some of them displayed clear-cut selectivity toward the viral G-quadruplexes with respect to the human telomeric G-quadruplexes. This feature translated into low nanomolar anti-HIV-1 activity toward two viral strains and encouraging selectivity indexes. The selectivity depended on specific recognition of LTR loop residues; the mechanism of action was ascribed to inhibition of LTR promoter activity in cells. This is the first example of G-quadruplex ligands that show increased selectivity toward the viral G-quadruplexes and display remarkable antiviral activity.",2015 Dec 24,"['Perrone, Rosalba', 'Doria, Filippo', 'Butovskaya, Elena', 'Frasson, Ilaria', 'Botti, Silvia', 'Scalabrin, Matteo', 'Lago, Sara', 'Grande, Vincenzo', 'Nadai, Matteo', 'Freccero, Mauro', 'Richter, Sara N.']",J Med Chem,,,False
16b7f68551e24898021ef6f3ba87149381fb0dd0,PMC,"Porcine Epidemic Diarrhea Virus and Discovery of a Recombinant Swine Enteric Coronavirus, Italy",http://dx.doi.org/10.3201/eid2201.150544,PMC4696687,26689738,NO-CC CODE,Porcine epidemic diarrhea virus (PEDV) has been detected sporadically in Italy since the 1990s. We report the phylogenetic relationship of swine enteric coronaviruses collected in Italy during 2007–2014 and identify a drastic shift in PEDV strain variability and a new swine enteric coronavirus generated by recombination of transmissible gastroenteritis virus and PEDV.,2016 Jan,"['Boniotti, M. Beatrice', 'Papetti, Alice', 'Lavazza, Antonio', 'Alborali, Giovanni', 'Sozzi, Enrica', 'Chiapponi, Chiara', 'Faccini, Silvia', 'Bonilauri, Paolo', 'Cordioli, Paolo', 'Marthaler, Douglas']",Emerg Infect Dis,,,True
d5448306c493aaa77174e9140427688e0f9c1824,PMC,"Porcine Epidemic Diarrhea Virus and Discovery of a Recombinant Swine Enteric Coronavirus, Italy",http://dx.doi.org/10.3201/eid2201.150544,PMC4696687,26689738,NO-CC CODE,Porcine epidemic diarrhea virus (PEDV) has been detected sporadically in Italy since the 1990s. We report the phylogenetic relationship of swine enteric coronaviruses collected in Italy during 2007–2014 and identify a drastic shift in PEDV strain variability and a new swine enteric coronavirus generated by recombination of transmissible gastroenteritis virus and PEDV.,2016 Jan,"['Boniotti, M. Beatrice', 'Papetti, Alice', 'Lavazza, Antonio', 'Alborali, Giovanni', 'Sozzi, Enrica', 'Chiapponi, Chiara', 'Faccini, Silvia', 'Bonilauri, Paolo', 'Cordioli, Paolo', 'Marthaler, Douglas']",Emerg Infect Dis,,,True
b8cce26d679d7fe229d2694978be17b229508320,PMC,"Anticipated Negative Responses by Students to Possible Ebola Virus Outbreak, Guangzhou, China",http://dx.doi.org/10.3201/eid2201.150898,PMC4696696,26690661,NO-CC CODE,,2016 Jan,"['Lau, Joseph T.F.', 'Wang, Zixin', 'Kim, Yoona', 'Gu, Jing', 'Wu, Anise M.S.', 'Zhou, Qianling', 'Hao, Chun', 'Cheng, Perry', 'Hao, Yuantao']",Emerg Infect Dis,,,True
5f5654de54f2b6b57364b6e637723e5a3d97fdd3,PMC,"Anticipated Negative Responses by Students to Possible Ebola Virus Outbreak, Guangzhou, China",http://dx.doi.org/10.3201/eid2201.150898,PMC4696696,26690661,NO-CC CODE,,2016 Jan,"['Lau, Joseph T.F.', 'Wang, Zixin', 'Kim, Yoona', 'Gu, Jing', 'Wu, Anise M.S.', 'Zhou, Qianling', 'Hao, Chun', 'Cheng, Perry', 'Hao, Yuantao']",Emerg Infect Dis,,,False
cdbf113c93f807ee1853027325c17d3d00dd871c,PMC,"Variations in Spike Glycoprotein Gene of MERS-CoV, South Korea, 2015",http://dx.doi.org/10.3201/eid2201.151055,PMC4696701,26691200,NO-CC CODE,"An outbreak of nosocomial infections with Middle East respiratory syndrome coronavirus occurred in South Korea in May 2015. Spike glycoprotein genes of virus strains from South Korea were closely related to those of strains from Riyadh, Saudi Arabia. However, virus strains from South Korea showed strain-specific variations.",2016 Jan,"['Kim, Dae-Won', 'Kim, You-Jin', 'Park, Sung Han', 'Yun, Mi-Ran', 'Yang, Jeong-Sun', 'Kang, Hae Ji', 'Han, Young Woo', 'Lee, Han Saem', 'Man Kim, Heui', 'Kim, Hak', 'Kim, A-Reum', 'Heo, Deok Rim', 'Kim, Su Jin', 'Jeon, Jun Ho', 'Park, Deokbum', 'Kim, Joo Ae', 'Cheong, Hyang-Min', 'Nam, Jeong-Gu', 'Kim, Kisoon', 'Kim, Sung Soon']",Emerg Infect Dis,,,True
7740cafff20a808697d26091851c30416eadfe53,PMC,"Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Illness in Humans, Saudi Arabia, 2014",http://dx.doi.org/10.3201/eid2201.151340,PMC4696714,26692185,NO-CC CODE,"Risk factors for primary Middle East respiratory syndrome coronavirus (MERS-CoV) illness in humans are incompletely understood. We identified all primary MERS-CoV cases reported in Saudi Arabia during March–November 2014 by excluding those with history of exposure to other cases of MERS-CoV or acute respiratory illness of unknown cause or exposure to healthcare settings within 14 days before illness onset. Using a case–control design, we assessed differences in underlying medical conditions and environmental exposures among primary case-patients and 2–4 controls matched by age, sex, and neighborhood. Using multivariable analysis, we found that direct exposure to dromedary camels during the 2 weeks before illness onset, as well as diabetes mellitus, heart disease, and smoking, were each independently associated with MERS-CoV illness. Further investigation is needed to better understand animal-to-human transmission of MERS-CoV.",2016 Jan,"['Alraddadi, Basem M.', 'Watson, John T.', 'Almarashi, Abdulatif', 'Abedi, Glen R.', 'Turkistani, Amal', 'Sadran, Musallam', 'Housa, Abeer', 'Almazroa, Mohammad A.', 'Alraihan, Naif', 'Banjar, Ayman', 'Albalawi, Eman', 'Alhindi, Hanan', 'Choudhry, Abdul Jamil', 'Meiman, Jonathan G.', 'Paczkowski, Magdalena', 'Curns, Aaron', 'Mounts, Anthony', 'Feikin, Daniel R.', 'Marano, Nina', 'Swerdlow, David L.', 'Gerber, Susan I.', 'Hajjeh, Rana', 'Madani, Tariq A.']",Emerg Infect Dis,,,True
825a2b4323d1b8c828b97bd48d66b3e748bea470,PMC,"Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Illness in Humans, Saudi Arabia, 2014",http://dx.doi.org/10.3201/eid2201.151340,PMC4696714,26692185,NO-CC CODE,"Risk factors for primary Middle East respiratory syndrome coronavirus (MERS-CoV) illness in humans are incompletely understood. We identified all primary MERS-CoV cases reported in Saudi Arabia during March–November 2014 by excluding those with history of exposure to other cases of MERS-CoV or acute respiratory illness of unknown cause or exposure to healthcare settings within 14 days before illness onset. Using a case–control design, we assessed differences in underlying medical conditions and environmental exposures among primary case-patients and 2–4 controls matched by age, sex, and neighborhood. Using multivariable analysis, we found that direct exposure to dromedary camels during the 2 weeks before illness onset, as well as diabetes mellitus, heart disease, and smoking, were each independently associated with MERS-CoV illness. Further investigation is needed to better understand animal-to-human transmission of MERS-CoV.",2016 Jan,"['Alraddadi, Basem M.', 'Watson, John T.', 'Almarashi, Abdulatif', 'Abedi, Glen R.', 'Turkistani, Amal', 'Sadran, Musallam', 'Housa, Abeer', 'Almazroa, Mohammad A.', 'Alraihan, Naif', 'Banjar, Ayman', 'Albalawi, Eman', 'Alhindi, Hanan', 'Choudhry, Abdul Jamil', 'Meiman, Jonathan G.', 'Paczkowski, Magdalena', 'Curns, Aaron', 'Mounts, Anthony', 'Feikin, Daniel R.', 'Marano, Nina', 'Swerdlow, David L.', 'Gerber, Susan I.', 'Hajjeh, Rana', 'Madani, Tariq A.']",Emerg Infect Dis,,,False
b27756adff17efe99584415760407f3feb51014c,PMC,"Multifacility Outbreak of Middle East Respiratory Syndrome in Taif, Saudi Arabia",http://dx.doi.org/10.3201/eid2201.151370,PMC4696715,26692003,NO-CC CODE,"Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is a novel respiratory pathogen first reported in 2012. During September 2014–January 2015, an outbreak of 38 cases of MERS was reported from 4 healthcare facilities in Taif, Saudi Arabia; 21 of the 38 case-patients died. Clinical and public health records showed that 13 patients were healthcare personnel (HCP). Fifteen patients, including 4 HCP, were associated with 1 dialysis unit. Three additional HCP in this dialysis unit had serologic evidence of MERS-CoV infection. Viral RNA was amplified from acute-phase serum specimens of 15 patients, and full spike gene-coding sequencing was obtained from 10 patients who formed a discrete cluster; sequences from specimens of 9 patients were closely related. Similar gene sequences among patients unlinked by time or location suggest unrecognized viral transmission. Circulation persisted in multiple healthcare settings over an extended period, underscoring the importance of strengthening MERS-CoV surveillance and infection-control practices.",2016 Jan,"['Assiri, Abdullah', 'Abedi, Glen R.', 'Saeed, Abdulaziz A. Bin', 'Abdalla, Mutwakil A.', 'al-Masry, Malak', 'Choudhry, Abdul Jamil', 'Lu, Xiaoyan', 'Erdman, Dean D.', 'Tatti, Kathleen', 'Binder, Alison M.', 'Rudd, Jessica', 'Tokars, Jerome', 'Miao, Congrong', 'Alarbash, Hussain', 'Nooh, Randa', 'Pallansch, Mark', 'Gerber, Susan I.', 'Watson, John T.']",Emerg Infect Dis,,,True
4a1e916ed5c14a6c0e5e4587827a4dde53756f52,PMC,"Multifacility Outbreak of Middle East Respiratory Syndrome in Taif, Saudi Arabia",http://dx.doi.org/10.3201/eid2201.151370,PMC4696715,26692003,NO-CC CODE,"Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is a novel respiratory pathogen first reported in 2012. During September 2014–January 2015, an outbreak of 38 cases of MERS was reported from 4 healthcare facilities in Taif, Saudi Arabia; 21 of the 38 case-patients died. Clinical and public health records showed that 13 patients were healthcare personnel (HCP). Fifteen patients, including 4 HCP, were associated with 1 dialysis unit. Three additional HCP in this dialysis unit had serologic evidence of MERS-CoV infection. Viral RNA was amplified from acute-phase serum specimens of 15 patients, and full spike gene-coding sequencing was obtained from 10 patients who formed a discrete cluster; sequences from specimens of 9 patients were closely related. Similar gene sequences among patients unlinked by time or location suggest unrecognized viral transmission. Circulation persisted in multiple healthcare settings over an extended period, underscoring the importance of strengthening MERS-CoV surveillance and infection-control practices.",2016 Jan,"['Assiri, Abdullah', 'Abedi, Glen R.', 'Saeed, Abdulaziz A. Bin', 'Abdalla, Mutwakil A.', 'al-Masry, Malak', 'Choudhry, Abdul Jamil', 'Lu, Xiaoyan', 'Erdman, Dean D.', 'Tatti, Kathleen', 'Binder, Alison M.', 'Rudd, Jessica', 'Tokars, Jerome', 'Miao, Congrong', 'Alarbash, Hussain', 'Nooh, Randa', 'Pallansch, Mark', 'Gerber, Susan I.', 'Watson, John T.']",Emerg Infect Dis,,,True
4c9829439f94ee330a01958f332a4d8f6e8b438f,PMC,"Objective Determination of End of MERS Outbreak, South Korea, 2015",http://dx.doi.org/10.3201/eid2201.151383,PMC4696716,26689765,NO-CC CODE,,2016 Jan,"['Nishiura, Hiroshi', 'Miyamatsu, Yuichiro', 'Mizumoto, Kenji']",Emerg Infect Dis,,,True
019ede0c6f1c02b64dea8e05e3bc8c7cb5811fae,PMC,"Objective Determination of End of MERS Outbreak, South Korea, 2015",http://dx.doi.org/10.3201/eid2201.151383,PMC4696716,26689765,NO-CC CODE,,2016 Jan,"['Nishiura, Hiroshi', 'Miyamatsu, Yuichiro', 'Mizumoto, Kenji']",Emerg Infect Dis,,,True
cf811730e853bc23b3ce2978034940208bfa37f5,PMC,Multiorgan WU Polyomavirus Infection in Bone Marrow Transplant Recipient,http://dx.doi.org/10.3201/eid2201.151384,PMC4696717,26691850,NO-CC CODE,"WU polyomavirus (WUPyV) was detected in a bone marrow transplant recipient with severe acute respiratory distress syndrome who died in 2001. Crystalline lattices of polyomavirus-like particles were observed in the patient’s lung by electron microscopy. WUPyV was detected in the lung and other tissues by real-time quantitative PCR and identified in the lung and trachea by immunohistochemistry. A subset of WUPyV-positive cells in the lung had morphologic features of macrophages. Although the role of WUPyV as a human pathogen remains unclear, these results clearly demonstrate evidence for infection of respiratory tract tissues in this patient.",2016 Jan,"['Siebrasse, Erica A.', 'Nguyen, Nang L.', 'Willby, Melisa J.', 'Erdman, Dean D.', 'Menegus, Marilyn A.', 'Wang, David']",Emerg Infect Dis,,,True
4461e9c905b651248f56c1d107331240b706eeb4,PMC,"Surveillance for Coronaviruses in Bats, Lebanon and Egypt, 2013–2015",http://dx.doi.org/10.3201/eid2201.151397,PMC4696718,26689887,NO-CC CODE,,2016 Jan,"['Shehata, Mahmoud M.', 'Chu, Daniel K.W.', 'Gomaa, Mokhtar R.', 'AbiSaid, Mounir', 'El Shesheny, Rabeh', 'Kandeil, Ahmed', 'Bagato, Ola', 'Chan, Samuel M.S.', 'Barbour, Elie K.', 'Shaib, Houssam S.', 'McKenzie, Pamela P.', 'Webby, Richard J.', 'Ali, Mohamed A.', 'Peiris, Malik', 'Kayali, Ghazi']",Emerg Infect Dis,,,True
c2bd5bf1038d976b60d86a81c00d886c1af3c0da,PMC,"Surveillance for Coronaviruses in Bats, Lebanon and Egypt, 2013–2015",http://dx.doi.org/10.3201/eid2201.151397,PMC4696718,26689887,NO-CC CODE,,2016 Jan,"['Shehata, Mahmoud M.', 'Chu, Daniel K.W.', 'Gomaa, Mokhtar R.', 'AbiSaid, Mounir', 'El Shesheny, Rabeh', 'Kandeil, Ahmed', 'Bagato, Ola', 'Chan, Samuel M.S.', 'Barbour, Elie K.', 'Shaib, Houssam S.', 'McKenzie, Pamela P.', 'Webby, Richard J.', 'Ali, Mohamed A.', 'Peiris, Malik', 'Kayali, Ghazi']",Emerg Infect Dis,,,True
82ca3ab5d05e7d31f2dcea84251a1eba8aa3f546,PMC,Joint China-US Call for Employing a Transdisciplinary Approach to Emerging Infectious Diseases,http://dx.doi.org/10.1007/s10393-015-1060-1,PMC4700097,26646835,NO-CC CODE,,2015 Dec 8,"['Mazet, Jonna A. K.', 'Wei, Qin', 'Zhao, Guoping', 'Cummings, Derek A. T.', 'Desmond, James Stephen', 'Rosenthal, Joshua', 'King, Charles H.', 'Cao, Wuchun', 'Chmura, Aleksei A.', 'Hagan, Emily A.', 'Zhang, Shuyi', 'Xiao, Xiangming', 'Xu, Jianguo', 'Shi, Zhengli', 'Feng, Feng', 'Liu, Xiuping', 'Pan, Weiqing', 'Zhu, Guangjian', 'Zuo, Liyao', 'Daszak, Peter']",Ecohealth,,,True
16b0744424f02e01fe2f01b3ea03e2862f1359fc,PMC,"Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation",http://dx.doi.org/10.1093/nar/gkv1189,PMC4702849,26553804,NO-CC CODE,"The RefSeq project at the National Center for Biotechnology Information (NCBI) maintains and curates a publicly available database of annotated genomic, transcript, and protein sequence records (http://www.ncbi.nlm.nih.gov/refseq/). The RefSeq project leverages the data submitted to the International Nucleotide Sequence Database Collaboration (INSDC) against a combination of computation, manual curation, and collaboration to produce a standard set of stable, non-redundant reference sequences. The RefSeq project augments these reference sequences with current knowledge including publications, functional features and informative nomenclature. The database currently represents sequences from more than 55 000 organisms (>4800 viruses, >40 000 prokaryotes and >10 000 eukaryotes; RefSeq release 71), ranging from a single record to complete genomes. This paper summarizes the current status of the viral, prokaryotic, and eukaryotic branches of the RefSeq project, reports on improvements to data access and details efforts to further expand the taxonomic representation of the collection. We also highlight diverse functional curation initiatives that support multiple uses of RefSeq data including taxonomic validation, genome annotation, comparative genomics, and clinical testing. We summarize our approach to utilizing available RNA-Seq and other data types in our manual curation process for vertebrate, plant, and other species, and describe a new direction for prokaryotic genomes and protein name management.",2016 Jan 4,"[""O'Leary, Nuala A."", 'Wright, Mathew W.', 'Brister, J. Rodney', 'Ciufo, Stacy', 'Haddad, Diana', 'McVeigh, Rich', 'Rajput, Bhanu', 'Robbertse, Barbara', 'Smith-White, Brian', 'Ako-Adjei, Danso', 'Astashyn, Alexander', 'Badretdin, Azat', 'Bao, Yiming', 'Blinkova, Olga', 'Brover, Vyacheslav', 'Chetvernin, Vyacheslav', 'Choi, Jinna', 'Cox, Eric', 'Ermolaeva, Olga', 'Farrell, Catherine M.', 'Goldfarb, Tamara', 'Gupta, Tripti', 'Haft, Daniel', 'Hatcher, Eneida', 'Hlavina, Wratko', 'Joardar, Vinita S.', 'Kodali, Vamsi K.', 'Li, Wenjun', 'Maglott, Donna', 'Masterson, Patrick', 'McGarvey, Kelly M.', 'Murphy, Michael R.', ""O'Neill, Kathleen"", 'Pujar, Shashikant', 'Rangwala, Sanjida H.', 'Rausch, Daniel', 'Riddick, Lillian D.', 'Schoch, Conrad', 'Shkeda, Andrei', 'Storz, Susan S.', 'Sun, Hanzhen', 'Thibaud-Nissen, Francoise', 'Tolstoy, Igor', 'Tully, Raymond E.', 'Vatsan, Anjana R.', 'Wallin, Craig', 'Webb, David', 'Wu, Wendy', 'Landrum, Melissa J.', 'Kimchi, Avi', 'Tatusova, Tatiana', 'DiCuccio, Michael', 'Kitts, Paul', 'Murphy, Terence D.', 'Pruitt, Kim D.']",Nucleic Acids Res,,,True
819902e2222b531ae0a6016763e43618b2988516,PMC,Database resources of the National Center for Biotechnology Information,http://dx.doi.org/10.1093/nar/gkv1290,PMC4702911,26615191,NO-CC CODE,"The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank(®) nucleic acid sequence database and the PubMed database of citations and abstracts for published life science journals. Additional NCBI resources focus on literature (PubMed Central (PMC), Bookshelf and PubReader), health (ClinVar, dbGaP, dbMHC, the Genetic Testing Registry, HIV-1/Human Protein Interaction Database and MedGen), genomes (BioProject, Assembly, Genome, BioSample, dbSNP, dbVar, Epigenomics, the Map Viewer, Nucleotide, Probe, RefSeq, Sequence Read Archive, the Taxonomy Browser and the Trace Archive), genes (Gene, Gene Expression Omnibus (GEO), HomoloGene, PopSet and UniGene), proteins (Protein, the Conserved Domain Database (CDD), COBALT, Conserved Domain Architecture Retrieval Tool (CDART), the Molecular Modeling Database (MMDB) and Protein Clusters) and chemicals (Biosystems and the PubChem suite of small molecule databases). The Entrez system provides search and retrieval operations for most of these databases. Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized datasets. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.",2016 Jan 4,,Nucleic Acids Res,,,True
6658283efba628db14a76984b7d3f39d79712f4c,PMC,Genome-wide Analysis of Epstein-Barr Virus (EBV) Integration and Strain in C666-1 and Raji Cells,http://dx.doi.org/10.7150/jca.13150,PMC4716855,26819646,NO-CC CODE,"EBV is a key risk factor for many malignancy diseases such as nasopharyngeal carcinoma (NPC) and Burkitt lymphoma (BL). EBV integration has been reported, but its scale and impact to cancer development is remains unclear. C666-1 (NPC cell line) and Raji (BL cell line) are commonly studied EBV-positive cancer cells. A rare few EBV integration sites in Raji were found in previous research by traditional methods. To deeply survey EBV integration, we sequenced C666-1 and Raji whole genomes by the next generation sequencing (NGS) technology and a total of 909 breakpoints were detected in the two cell lines. Moreover, we observed that the number of integration sites was positive correlated with the total amount of chromosome structural variations (SVs) and copy number structural variations (CNVs), and most breakpoints located inside or nearby genome structural variations regions. It suggested that host genome instability provided an opportunity for EBV integration on one hand and the integration aggravated host genome instability on the other hand. Then, we respectively assembled the C666-1 and Raji EBV strains which would be useful resources for EBV-relative studies. Thus, we report the most comprehensive characterization of EBV integration in NPC cell and BL cell, and EBV shows the wide range and random integration to increase the tumorigenesis. The NGS provides an incomparable level of resolution on EBV integration and a convenient approach to obtain viral strain compared to any research technology before.",2016 Jan 1,"['Xiao, Kai', 'Yu, Zhengyuan', 'Li, Xiayu', 'Li, Xiaoling', 'Tang, Ke', 'Tu, Chaofeng', 'Qi, Peng', 'Liao, Qianjin', 'Chen, Pan', 'Zeng, Zhaoyang', 'Li, Guiyuan', 'Xiong, Wei']",J Cancer,,,True
ab9ebe0a429625b365db7684fca907c5fd2c5e31,PMC,Risk communication in times of crisis: Pitfalls and challenges in ensuring preparedness instead of hysterics,http://dx.doi.org/10.15252/embr.201541678,PMC4718415,26658329,NO-CC CODE,The Ebola outbreak in West Africa is an instructive lesson on the difficulties of risk communication in times of crisis. The most effective strategy to improve communication during a crisis is to build public trust in officials and academics long before disaster strikes. [Image: see text],2016 Jan 9,"Böl, Gaby‐Fleur",EMBO Rep,,,True
8604d285ad83e111704365b6dc4cc60e03d71b49,PMC,N-Methylation as a Strategy for Enhancing the Affinity and Selectivity of RNA-binding Peptides: Application to the HIV-1 Frameshift-Stimulating RNA,http://dx.doi.org/10.1021/acschembio.5b00682,PMC4720131,26496521,NO-CC CODE,"[Image: see text] Human Immunodeficiency Virus (HIV) type 1 uses a −1 programmed ribosomal frameshift (−1 PRF) event to translate its enzymes from the same transcript used to encode the virus’ structural proteins. The frequency of this event is highly regulated, and significant deviation from the normal 5–10% frequency has been demonstrated to decrease viral infectivity. Frameshifting is primarily regulated by the Frameshift Stimulatory Signal RNA (FSS-RNA), a thermodynamically stable, highly conserved stem loop that has been proposed as a therapeutic target. We describe the design, synthesis, and testing of a series of N-methyl peptides able to bind the HIV-1 FSS RNA stem loop with low nanomolar affinity and high selectivity. Surface plasmon resonance (SPR) data indicates increased affinity is a reflection of a substantially enhanced on rate. Compounds readily penetrate cell membranes and inhibit HIV infectivity in a pseudotyped virus assay. Viral infectivity inhibition correlates with compound-dependent changes in the ratios of Gag and Gag-Pol in virus particles. As the first compounds with both single digit nanomolar affinities for the FSS RNA and an ability to inhibit HIV in cells, these studies support the use of N-methylation for enhancing the affinity, selectivity, and bioactivity of RNA-binding peptides.",2016 Jan 15,"['Hilimire, Thomas\nA.', 'Bennett, Ryan P.', 'Stewart, Ryan A.', 'Garcia-Miranda, Pablo', 'Blume, Alex', 'Becker, Jordan', 'Sherer, Nathan', 'Helms, Eric D.', 'Butcher, Samuel E.', 'Smith, Harold C.', 'Miller, Benjamin L.']",ACS Chem Biol,,,True
9afb35f53239d7fc6c241632cef92d1ed9742ef6,PMC,N-Methylation as a Strategy for Enhancing the Affinity and Selectivity of RNA-binding Peptides: Application to the HIV-1 Frameshift-Stimulating RNA,http://dx.doi.org/10.1021/acschembio.5b00682,PMC4720131,26496521,NO-CC CODE,"[Image: see text] Human Immunodeficiency Virus (HIV) type 1 uses a −1 programmed ribosomal frameshift (−1 PRF) event to translate its enzymes from the same transcript used to encode the virus’ structural proteins. The frequency of this event is highly regulated, and significant deviation from the normal 5–10% frequency has been demonstrated to decrease viral infectivity. Frameshifting is primarily regulated by the Frameshift Stimulatory Signal RNA (FSS-RNA), a thermodynamically stable, highly conserved stem loop that has been proposed as a therapeutic target. We describe the design, synthesis, and testing of a series of N-methyl peptides able to bind the HIV-1 FSS RNA stem loop with low nanomolar affinity and high selectivity. Surface plasmon resonance (SPR) data indicates increased affinity is a reflection of a substantially enhanced on rate. Compounds readily penetrate cell membranes and inhibit HIV infectivity in a pseudotyped virus assay. Viral infectivity inhibition correlates with compound-dependent changes in the ratios of Gag and Gag-Pol in virus particles. As the first compounds with both single digit nanomolar affinities for the FSS RNA and an ability to inhibit HIV in cells, these studies support the use of N-methylation for enhancing the affinity, selectivity, and bioactivity of RNA-binding peptides.",2016 Jan 15,"['Hilimire, Thomas\nA.', 'Bennett, Ryan P.', 'Stewart, Ryan A.', 'Garcia-Miranda, Pablo', 'Blume, Alex', 'Becker, Jordan', 'Sherer, Nathan', 'Helms, Eric D.', 'Butcher, Samuel E.', 'Smith, Harold C.', 'Miller, Benjamin L.']",ACS Chem Biol,,,True
b60d9bb4f4f516bdf9e4e376e536c07111a940f4,PMC,"Microevolution of Outbreak-Associated Middle East Respiratory Syndrome Coronavirus, South Korea, 2015",http://dx.doi.org/10.3201/eid2202.151700,PMC4734539,26814649,NO-CC CODE,"During the 2015 Middle East respiratory syndrome coronavirus outbreak in South Korea, we sequenced full viral genomes of strains isolated from 4 patients early and late during infection. Patients represented at least 4 generations of transmission. We found no evidence of changes in the evolutionary rate and no reason to suspect adaptive changes in viral proteins.",2016 Feb,"['Seong, Moon-Woo', 'Kim, So Yeon', 'Corman, Victor Max', 'Kim, Taek Soo', 'Cho, Sung Im', 'Kim, Man Jin', 'Lee, Seung Jun', 'Lee, Jee-Soo', 'Seo, Soo Hyun', 'Ahn, Ji Soo', 'Yu, Byeong Su', 'Park, Nare', 'Oh, Myoung-don', 'Park, Wan Beom', 'Lee, Ji Yeon', 'Kim, Gayeon', 'Joh, Joon Sung', 'Jeong, Ina', 'Kim, Eui Chong', 'Drosten, Christian', 'Park, Sung Sup']",Emerg Infect Dis,,,True
0ed5e21aa97afbcd81aea8fb49610f4263b45475,PMC,"Microevolution of Outbreak-Associated Middle East Respiratory Syndrome Coronavirus, South Korea, 2015",http://dx.doi.org/10.3201/eid2202.151700,PMC4734539,26814649,NO-CC CODE,"During the 2015 Middle East respiratory syndrome coronavirus outbreak in South Korea, we sequenced full viral genomes of strains isolated from 4 patients early and late during infection. Patients represented at least 4 generations of transmission. We found no evidence of changes in the evolutionary rate and no reason to suspect adaptive changes in viral proteins.",2016 Feb,"['Seong, Moon-Woo', 'Kim, So Yeon', 'Corman, Victor Max', 'Kim, Taek Soo', 'Cho, Sung Im', 'Kim, Man Jin', 'Lee, Seung Jun', 'Lee, Jee-Soo', 'Seo, Soo Hyun', 'Ahn, Ji Soo', 'Yu, Byeong Su', 'Park, Nare', 'Oh, Myoung-don', 'Park, Wan Beom', 'Lee, Ji Yeon', 'Kim, Gayeon', 'Joh, Joon Sung', 'Jeong, Ina', 'Kim, Eui Chong', 'Drosten, Christian', 'Park, Sung Sup']",Emerg Infect Dis,,,False
f71c5fc3040dbc1fa7419bf6004a53353f32590b,PMC,Time for T? Immunoinformatics addresses vaccine design for neglected tropical and emerging infectious diseases,http://dx.doi.org/10.1586/14760584.2015.955478,PMC4743591,25193104,NO-CC CODE,"Vaccines have been invaluable for global health, saving lives and reducing healthcare costs, while also raising the quality of human life. However, newly emerging infectious diseases (EID) and more well-established tropical disease pathogens present complex challenges to vaccine developers; in particular, neglected tropical diseases, which are most prevalent among the world’s poorest, include many pathogens with large sizes, multistage life cycles and a variety of nonhuman vectors. EID such as MERS-CoV and H7N9 are highly pathogenic for humans. For many of these pathogens, while their genomes are available, immune correlates of protection are currently unknown. These complexities make developing vaccines for EID and neglected tropical diseases all the more difficult. In this review, we describe the implementation of an immunoinformatics-driven approach to systematically search for key determinants of immunity in newly available genome sequence data and design vaccines. This approach holds promise for the development of 21st century vaccines, improving human health everywhere.",2015 Jan 2,"['Terry, Frances E', 'Moise, Leonard', 'Martin, Rebecca F', 'Torres, Melissa', 'Pilotte, Nils', 'Williams, Steven A', 'De Groot, Anne S']",Expert Rev Vaccines,,,True
940fe55ad5d57c4e58076fb38e4aae64694a5baf,PMC,Delivery System of CpG Oligodeoxynucleotides through Eliciting an Effective T cell Immune Response against Melanoma in Mice,http://dx.doi.org/10.7150/jca.12899,PMC4747877,26918036,NO-CC CODE,"Purpose: In order to improve the immunogenicity of whole tumor cell lysate for tumor vaccine, we have designed a series of CpG ODNs to study their transport and to evaluate their anti-tumor activity in B16 melanoma mouse models. Methods: In this study, we investigated whether C-class CpG ODN (CpG ODN-685) could facilitate tumor cell lysate to induce vigorous anti-tumor activity against tumors in mice both prophylactically and therapeutically. Results: It was found that the combination of tumor cell lysate and CpG ODN-685 could inhibit the growth of B16 melanoma and prolong the survival of tumor-bearing mice. Moreover CpG ODN-685 with the addition of tumor cell lysate can also cause the generation of tumor specific immune memory by inducing specific cytotoxic T lymphocytes and helper T lymphocytes in mice. Conclusion: The results suggest that CpG ODN-685 could be developed as an efficient adjuvant for tumor vaccines against melanoma.",2016 Jan 5,"['Sun, Wei', 'Fang, Mingli', 'Chen, Yajing', 'Yang, Zhaogang', 'Xiao, Yue', 'Wan, Min', 'Wang, Hua', 'Yu, Yongli', 'Wang, Liying']",J Cancer,,,True
b70352cde76b15b3f8eb60a492ad27bd0a8c4a20,PMC,Association between Severity of MERS-CoV Infection and Incubation Period,http://dx.doi.org/10.3201/eid2203.151437,PMC4766874,26890291,NO-CC CODE,"We analyzed data for 170 patients in South Korea who had laboratory-confirmed infection with Middle East respiratory syndrome coronavirus. A longer incubation period was associated with a reduction in the risk for death (adjusted odds ratio/1-day increase in incubation period 0.83, 95% credibility interval 0.68–1.03).",2016 Mar,"['Virlogeux, Victor', 'Park, Minah', 'Wu, Joseph T.', 'Cowling, Benjamin J.']",Emerg Infect Dis,,,True
68a2a48d4c67318b019928c9e1d1e896153a6cd2,PMC,Association between Severity of MERS-CoV Infection and Incubation Period,http://dx.doi.org/10.3201/eid2203.151437,PMC4766874,26890291,NO-CC CODE,"We analyzed data for 170 patients in South Korea who had laboratory-confirmed infection with Middle East respiratory syndrome coronavirus. A longer incubation period was associated with a reduction in the risk for death (adjusted odds ratio/1-day increase in incubation period 0.83, 95% credibility interval 0.68–1.03).",2016 Mar,"['Virlogeux, Victor', 'Park, Minah', 'Wu, Joseph T.', 'Cowling, Benjamin J.']",Emerg Infect Dis,,,True
3415b829bc37f09d2e984666450d1a3af3f448d3,PMC,"Middle East Respiratory Syndrome Coronavirus during Pregnancy, Abu Dhabi, United Arab Emirates, 2013",http://dx.doi.org/10.3201/eid2203.151049,PMC4766880,26890613,NO-CC CODE,"As of June 19, 2015, the World Health Organization had received 1,338 notifications of laboratory-confirmed infection with Middle East respiratory syndrome coronavirus (MERS-CoV). Little is known about the course of or treatment for MERS-CoV in pregnant women. We report a fatal case of MERS-CoV in a pregnant woman administered combination ribavirin–peginterferon-α therapy.",2016 Mar,"['Malik, Asim', 'El Masry, Karim Medhat', 'Ravi, Mini', 'Sayed, Falak']",Emerg Infect Dis,,,True
c12f447d8fe4cc4602b52a31f1715e0cadedb6a1,PMC,"Absence of Middle East Respiratory Syndrome Coronavirus in Camelids, Kazakhstan, 2015",http://dx.doi.org/10.3201/eid2203.151284,PMC4766892,26889787,NO-CC CODE,,2016 Mar,"['Miguel, Eve', 'Perera, Ranawaka A.P.M.', 'Baubekova, Almagul', 'Chevalier, Véronique', 'Faye, Bernard', 'Akhmetsadykov, Nurlan', 'Ng, Chun Yin', 'Roger, François', 'Peiris, Malik']",Emerg Infect Dis,,,True
570862c4784b6f780726ec0548fc402a413146b4,PMC,EMMPRIN-Targeted Magnetic Nanoparticles for In Vivo Visualization and Regression of Acute Myocardial Infarction,http://dx.doi.org/10.7150/thno.13352,PMC4775864,26941847,NO-CC CODE,"Inhibition of extracellular matrix (ECM) degradation may represent a mechanism for cardiac protection against ischemia. Extracellular matrix metalloproteinase inducer (EMMPRIN) is highly expressed in response to acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including gelatinases MMP-2 and MMP-9. We targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles conjugated with the EMMPRIN binding peptide AP-9 (NAP9), or an AP-9 scrambled peptide as a negative control (NAPSC). We found that NAP9 binds to endogenous EMMPRIN in cultured HL1 myocytes and in mouse hearts subjected to ischemia/reperfusion (IR). Injection of NAP9 at the time of or one day after IR, was enough to reduce progression of myocardial cell death when compared to Control and NAPSC injected mice (infarct size in NAP9 injected mice: 32%±6.59 vs Control: 46%±9.04 or NAPSC injected mice: 48%±7.64). In the same way, cardiac parameters were recovered to almost healthy levels (LVEF NAP9 63% ± 7.24 vs Control 42% ± 4.74 or NAPSC 39% ± 6.44), whereas ECM degradation was also reduced as shown by inhibition of MMP-2 and MMP-9 activation. Cardiac magnetic resonance (CMR) scans have shown a signal enhancement in the left ventricle of NAP9 injected mice with respect to non-injected, and to mice injected with NAPSC. A positive correlation between CMR enhancement and Evans-Blue/TTC staining of infarct size was calculated (R:0.65). Taken together, these results point to EMMPRIN targeted nanoparticles as a new approach to the mitigation of ischemic/reperfusion injury.",2016 Feb 15,"['Cuadrado, Irene', 'Piedras, Maria Jose Garcia Miguel', 'Herruzo, Irene', 'Turpin, Maria del Carmen', 'Castejón, Borja', 'Reventun, Paula', 'Martin, Ana', 'Saura, Marta', 'Zamorano, Jose Luis', 'Zaragoza, Carlos']",Theranostics,,,True
382b6772598f7d07dde36a4377fe8e25302e212a,PMC,Critically ill patients with Middle East respiratory syndrome coronavirus infection,http://dx.doi.org/10.1186/s13054-016-1234-4,PMC4794852,26984370,NO-CC CODE,This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency medicine 2016. Other selected articles can be found online at http://www.biomedcentral.com/collections/annualupdate2016. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.,2016 Mar 16,"['Al-Dorzi, Hasan M.', 'Alsolamy, Sami', 'Arabi, Yaseen M.']",Crit Care,,,True
1c63b88923b15b7733aac9630ae9e73aa09c8e1d,PMC,Determinants and Drivers of Infectious Disease Threat Events in Europe,http://dx.doi.org/10.3201/eid2204.151073,PMC4806948,26982104,NO-CC CODE,"Infectious disease threat events (IDTEs) are increasing in frequency worldwide. We analyzed underlying drivers of 116 IDTEs detected in Europe during 2008–2013 by epidemic intelligence at the European Centre of Disease Prevention and Control. Seventeen drivers were identified and categorized into 3 groups: globalization and environment, sociodemographic, and public health systems. A combination of >2 drivers was responsible for most IDTEs. The driver category globalization and environment contributed to 61% of individual IDTEs, and the top 5 individual drivers of all IDTEs were travel and tourism, food and water quality, natural environment, global trade, and climate. Hierarchical cluster analysis of all drivers identified travel and tourism as a distinctly separate driver. Monitoring and modeling such disease drivers can help anticipate future IDTEs and strengthen control measures. More important, intervening directly on these underlying drivers can diminish the likelihood of the occurrence of an IDTE and reduce the associated human and economic costs.",2016 Apr,"['Semenza, Jan C.', 'Lindgren, Elisabet', 'Balkanyi, Laszlo', 'Espinosa, Laura', 'Almqvist, My S.', 'Penttinen, Pasi', 'Rocklöv, Joacim']",Emerg Infect Dis,,,True
39ba47cc9e50b03f0de4eb4e1b0af22e0a5014a3,PMC,"Deletion Variants of Middle East Respiratory Syndrome Coronavirus from Humans, Jordan, 2015",http://dx.doi.org/10.3201/eid2204.152065,PMC4806954,26981770,NO-CC CODE,"We characterized Middle East respiratory syndrome coronaviruses from a hospital outbreak in Jordan in 2015. The viruses from Jordan were highly similar to isolates from Riyadh, Saudi Arabia, except for deletions in open reading frames 4a and 3. Transmissibility and pathogenicity of this strain remains to be determined.",2016 Apr,"['Lamers, Mart M.', 'Raj, V. Stalin', 'Shafei, Mah’d', 'Ali, Sami Sheikh', 'Abdallh, Sultan M.', 'Gazo, Mahmoud', 'Nofal, Samer', 'Lu, Xiaoyan', 'Erdman, Dean D.', 'Koopmans, Marion P.', 'Abdallat, Mohammad', 'Haddadin, Aktham', 'Haagmans, Bart L.']",Emerg Infect Dis,,,True
9e28573c983994a6dbe2a66276d05781cecc4100,PMC,"One Health: People, Animals, and the Environment",http://dx.doi.org/10.3201/eid2204.151887,PMC4806965,,NO-CC CODE,,2016 Apr,"Behravesh, Casey Barton",Emerg Infect Dis,,,False
fc00aeeb5cb014196c3a07fbd9db0c5e80b4a8c4,PMC,"Porcine Deltacoronavirus, Thailand, 2015",http://dx.doi.org/10.3201/eid2204.151852,PMC4806967,26982324,NO-CC CODE,,2016 Apr,"['Janetanakit, Taveesak', 'Lumyai, Mongkol', 'Bunpapong, Napawan', 'Boonyapisitsopa, Supanat', 'Chaiyawong, Supassama', 'Nonthabenjawan, Nutthawan', 'Kesdaengsakonwut, Sawang', 'Amonsin, Alongkorn']",Emerg Infect Dis,,,True
1447cbaffd1c03718da0534b7bfa97435cd3c78d,PMC,"Porcine Deltacoronavirus, Thailand, 2015",http://dx.doi.org/10.3201/eid2204.151852,PMC4806967,26982324,NO-CC CODE,,2016 Apr,"['Janetanakit, Taveesak', 'Lumyai, Mongkol', 'Bunpapong, Napawan', 'Boonyapisitsopa, Supanat', 'Chaiyawong, Supassama', 'Nonthabenjawan, Nutthawan', 'Kesdaengsakonwut, Sawang', 'Amonsin, Alongkorn']",Emerg Infect Dis,,,True
196744775d0812baf3fdb72bf700df2c99e36ac5,PMC,Exportations of Symptomatic Cases of MERS-CoV Infection to Countries outside the Middle East,http://dx.doi.org/10.3201/eid2204.150976,PMC4806968,27358972,NO-CC CODE,"In 2012, an outbreak of infection with Middle East respiratory syndrome coronavirus (MERS-CoV), was detected in the Arabian Peninsula. Modeling can produce estimates of the expected annual number of symptomatic cases of MERS-CoV infection exported and the likelihood of exportation from source countries in the Middle East to countries outside the region.",2016 Apr,"['Carias, Cristina', 'O’Hagan, Justin J.', 'Jewett, Amy', 'Gambhir, Manoj', 'Cohen, Nicole J.', 'Haber, Yoni', 'Pesik, Nicki', 'Swerdlow, David L.']",Emerg Infect Dis,,,True
a0aed635308ebac3b0e430d3c7722756638b1510,PMC,Exportations of Symptomatic Cases of MERS-CoV Infection to Countries outside the Middle East,http://dx.doi.org/10.3201/eid2204.150976,PMC4806968,27358972,NO-CC CODE,"In 2012, an outbreak of infection with Middle East respiratory syndrome coronavirus (MERS-CoV), was detected in the Arabian Peninsula. Modeling can produce estimates of the expected annual number of symptomatic cases of MERS-CoV infection exported and the likelihood of exportation from source countries in the Middle East to countries outside the region.",2016 Apr,"['Carias, Cristina', 'O’Hagan, Justin J.', 'Jewett, Amy', 'Gambhir, Manoj', 'Cohen, Nicole J.', 'Haber, Yoni', 'Pesik, Nicki', 'Swerdlow, David L.']",Emerg Infect Dis,,,True
713670f3bba541ae77e6ac7bb32c9ea27c01e19d,PMC,"Transmission of Middle East Respiratory Syndrome Coronavirus Infections in Healthcare Settings, Abu Dhabi",http://dx.doi.org/10.3201/eid2204.151615,PMC4806977,26981708,NO-CC CODE,"Middle East respiratory syndrome coronavirus (MERS-CoV) infections sharply increased in the Arabian Peninsula during spring 2014. In Abu Dhabi, United Arab Emirates, these infections occurred primarily among healthcare workers and patients. To identify and describe epidemiologic and clinical characteristics of persons with healthcare-associated infection, we reviewed laboratory-confirmed MERS-CoV cases reported to the Health Authority of Abu Dhabi during January 1, 2013–May 9, 2014. Of 65 case-patients identified with MERS-CoV infection, 27 (42%) had healthcare-associated cases. Epidemiologic and genetic sequencing findings suggest that 3 healthcare clusters of MERS-CoV infection occurred, including 1 that resulted in 20 infected persons in 1 hospital. MERS-CoV in healthcare settings spread predominantly before MERS-CoV infection was diagnosed, underscoring the importance of increasing awareness and infection control measures at first points of entry to healthcare facilities.",2016 Apr,"['Hunter, Jennifer C.', 'Nguyen, Duc', 'Aden, Bashir', 'Al Bandar, Zyad', 'Al Dhaheri, Wafa', 'Abu Elkheir, Kheir', 'Khudair, Ahmed', 'Al Mulla, Mariam', 'El Saleh, Feda', 'Imambaccus, Hala', 'Al Kaabi, Nawal', 'Sheikh, Farrukh Amin', 'Sasse, Jurgen', 'Turner, Andrew', 'Abdel Wareth, Laila', 'Weber, Stefan', 'Al Ameri, Asma', 'Abu Amer, Wesal', 'Alami, Negar N.', 'Bunga, Sudhir', 'Haynes, Lia M.', 'Hall, Aron J.', 'Kallen, Alexander J.', 'Kuhar, David', 'Pham, Huong', 'Pringle, Kimberly', 'Tong, Suxiang', 'Whitaker, Brett L.', 'Gerber, Susan I.', 'Al Hosani, Farida Ismail']",Emerg Infect Dis,,,True
c1a03657b225afb8628f4806530db7f57645ad54,PMC,CPT-cGMP Is A New Ligand of Epithelial Sodium Channels,http://dx.doi.org/10.7150/ijbs.13764,PMC4807156,27019621,NO-CC CODE,"Epithelial sodium channels (ENaC) are localized at the apical membrane of the epithelium, and are responsible for salt and fluid reabsorption. Renal ENaC takes up salt, thereby controlling salt content in serum. Loss-of-function ENaC mutations lead to low blood pressure due to salt-wasting, while gain-of-function mutations cause impaired sodium excretion and subsequent hypertension as well as hypokalemia. ENaC activity is regulated by intracellular and extracellular signals, including hormones, neurotransmitters, protein kinases, and small compounds. Cyclic nucleotides are broadly involved in stimulating protein kinase A and protein kinase G signaling pathways, and, surprisingly, also appear to have a role in regulating ENaC. Increasing evidence suggests that the cGMP analog, CPT-cGMP, activates αβγ-ENaC activity reversibly through an extracellular pathway in a dose-dependent manner. Furthermore, the parachlorophenylthio moiety and ribose 2'-hydroxy group of CPT-cGMP are essential for facilitating the opening of ENaC channels by this compound. Serving as an extracellular ligand, CPT-cGMP eliminates sodium self-inhibition, which is a novel mechanism for stimulating salt reabsorption in parallel to the traditional NO/cGMP/PKG signal pathway. In conclusion, ENaC may be a druggable target for CPT-cGMP, leading to treatments for kidney malfunctions in salt reabsorption.",2016 Jan 28,"['Ji, Hong-Long', 'Nie, Hong-Guang', 'Chang, Yongchang', 'Lian, Qizhou', 'Liu, Shan-Lu']",Int J Biol Sci,,,True
8970ef10049816050cb1bc5fbf600865a5996ad4,PMC,Base-By-Base: Single nucleotide-level analysis of whole viral genome alignments,http://dx.doi.org/10.1186/1471-2105-5-96,PMC481056,15253776,NO-CC CODE,"BACKGROUND: With ever increasing numbers of closely related virus genomes being sequenced, it has become desirable to be able to compare two genomes at a level more detailed than gene content because two strains of an organism may share the same set of predicted genes but still differ in their pathogenicity profiles. For example, detailed comparison of multiple isolates of the smallpox virus genome (each approximately 200 kb, with 200 genes) is not feasible without new bioinformatics tools. RESULTS: A software package, Base-By-Base, has been developed that provides visualization tools to enable researchers to 1) rapidly identify and correct alignment errors in large, multiple genome alignments; and 2) generate tabular and graphical output of differences between the genomes at the nucleotide level. Base-By-Base uses detailed annotation information about the aligned genomes and can list each predicted gene with nucleotide differences, display whether variations occur within promoter regions or coding regions and whether these changes result in amino acid substitutions. Base-By-Base can connect to our mySQL database (Virus Orthologous Clusters; VOCs) to retrieve detailed annotation information about the aligned genomes or use information from text files. CONCLUSION: Base-By-Base enables users to quickly and easily compare large viral genomes; it highlights small differences that may be responsible for important phenotypic differences such as virulence. It is available via the Internet using Java Web Start and runs on Macintosh, PC and Linux operating systems with the Java 1.4 virtual machine.",2004 Jul 14,"['Brodie, Ryan', 'Smith, Alex J', 'Roper, Rachel L', 'Tcherepanov, Vasily', 'Upton, Chris']",BMC Bioinformatics,,,True
2fbf85467d8268da83e90d1cd249978262c8f2a5,PMC,"Characteristics of Group A Streptococcus Strains Circulating during Scarlet Fever Epidemic, Beijing, China, 2011",http://dx.doi.org/10.3201/eid1906.121020,PMC4816378,23735582,NO-CC CODE,"Scarlet fever is one of a variety of diseases caused by group A Streptococcus (GAS). During 2011, a scarlet fever epidemic characterized by peak monthly incidence rates 2.9–6.7 times higher than those in 2006–2010 occurred in Beijing, China. During the epidemic, hospital-based enhanced surveillance for scarlet fever and pharyngitis was conducted to determine characteristics of circulating GAS strains. The surveillance identified 3,359 clinical cases of scarlet fever or pharyngitis. GAS was isolated from 647 of the patients; 76.4% of the strains were type emm12, and 17.1% were emm1. Almost all isolates harbored superantigens speC and ssa. All isolates were susceptible to penicillin, and resistance rates were 96.1% to erythromycin, 93.7% to tetracycline, and 79.4% to clindamycin. Because emm12 type GAS is not the predominant type in other countries, wider surveillance for the possible spread of emm12 type GAS from China to other countries is warranted.",2013 Jun,"['Yang, Peng', 'Peng, Xiaomin', 'Zhang, Daitao', 'Wu, Shuangsheng', 'Liu, Yimeng', 'Cui, Shujuan', 'Lu, Guilan', 'Duan, Wei', 'Shi, Weixian', 'Liu, Shuang', 'Li, Jing', 'Wang, Quanyi']",Emerg Infect Dis,,,True
7a5bc9a848fbf197657c7ccb6f8d7ae361a4b9d2,PMC,More Is More,http://dx.doi.org/10.3201/eid1906.AC1906,PMC4816380,23735517,NO-CC CODE,,2013 Jun,"Potter, Polyxeni",Emerg Infect Dis,,,True
642f87b9554dc5868a8b876c6f1df729023f5f30,PMC,Bioinformatics and Molecular Analysis of the Evolutionary Relationship between Bovine Rhinitis A Viruses and Foot-And-Mouth Disease Virus,http://dx.doi.org/10.4137/BBI.S37223,PMC4822724,27081310,NO-CC CODE,"Bovine rhinitis viruses (BRVs) cause mild respiratory disease of cattle. In this study, a near full-length genome sequence of a virus named RS3X (formerly classified as bovine rhinovirus type 1), isolated from infected cattle from the UK in the 1960s, was obtained and analyzed. Compared to other closely related Aphthoviruses, major differences were detected in the leader protease (L(pro)), P1, 2B, and 3A proteins. Phylogenetic analysis revealed that RS3X was a member of the species bovine rhinitis A virus (BRAV). Using different codon-based and branch-site selection models for Aphthoviruses, including BRAV RS3X and foot-and-mouth disease virus, we observed no clear evidence for genomic regions undergoing positive selection. However, within each of the BRV species, multiple sites under positive selection were detected. The results also suggest that the probability (determined by Recombination Detection Program) for recombination events between BRVs and other Aphthoviruses, including foot-and-mouth disease virus was not significant. In contrast, within BRVs, the probability of recombination increases. The data reported here provide genetic information to assist in the identification of diagnostic signatures and research tools for BRAV.",2016 Apr 4,"['Rai, Devendra K.', 'Lawrence, Paul', 'Pauszek, Steve J.', 'Piccone, Maria E.', 'Knowles, Nick J.', 'Rieder, Elizabeth']",Bioinform Biol Insights,,,True
4d96e256e0f1c90ff5456ab1146d85f17bbd3c02,PMC,Human bocavirus infections among children less than two years old in Iran during fall and winter 2012–2013,,PMC4833746,27092229,NO-CC CODE,BACKGROUND AND OBJECTIVES: Human bocavirus (HBoV) is a newly discovered parvovirus. It has been detected primarily in children with acute respiratory tract infections. This study was conducted to clarify the frequency and genotype circulation pattern of HBoV in Iran. MATERIALS AND METHODS: Conventional PCR was performed on throat swabs of patients less than two years of age with respiratory illnesses during fall and winter 2012–2013. RESULTS: HBoV virus DNA was detected in 15 of 140 samples (10.7 %). Sequencing and phylogenetic analysis on 5 samples showed that all were HBoV1. The positive samples were negative for influenza A and B viruses while co-infection with RSV was found in 2 (13.3%). CONCLUSION: This study adds to the body of knowledge about the role of HBoV in acute respiratory illnesses in children in Iran.,2016 Feb,"['Tabasi, Maryam', 'Mokhtari-Azad, Talat', 'Eshraghian, Mohammad Reza', 'Shadab, Azadeh', 'Shatizadeh, Somayeh', 'Shafiei-Jandaghi, Nazanin Zahra', 'Yavarian, Jila']",Iran J Microbiol,,,True
38961185beb38aa928232a73801aa76944468e07,PMC,Health Care Associated Middle East Respiratory Syndrome (MERS): A Case from Iran,,PMC4841994,27114729,NO-CC CODE,"Middle East respiratory syndrome coronavirus (MERS-CoV) Infection, has caused recurrent outbreaks worldwide. It is associated with severe morbidity and mortality, and is not treatable with the currently available antiviral therapies. We present a case of a 43 year-old male healthcare provider, who admitted with productive cough, dyspnea, myalgia, pleuritic chest pain and fever. Computed tomography (CT) showed bilateral ground glass opacities and consolidation. Sputum polymerase chain reaction (PCR) for MERS-coronavirus was positive.",2015,"['Moniri, Afshin', 'Marjani, Majid', 'Tabarsi, Payam', 'Yadegarynia, Davood', 'Nadji, Seyed Alireza']",Tanaffos,,,True
f4761a305755e1f614a75cc8ade098b09d005728,PMC,Plasmon-Enhanced Fluorescence Biosensors: a Review,http://dx.doi.org/10.1007/s11468-013-9660-5,PMC4846700,27330521,NO-CC CODE,"Surfaces of metallic films and metallic nanoparticles can strongly confine electromagnetic field through its coupling to propagating or localized surface plasmons. This interaction is associated with large enhancement of the field intensity and local optical density of states which provides means to increase excitation rate, raise quantum yield, and control far field angular distribution of fluorescence light emitted by organic dyes and quantum dots. Such emitters are commonly used as labels in assays for detection of chemical and biological species. Their interaction with surface plasmons allows amplifying fluorescence signal (brightness) that accompanies molecular binding events by several orders of magnitude. In conjunction with interfacial architectures for the specific capture of target analyte on a metallic surface, plasmon-enhanced fluorescence (PEF) that is also referred to as metal-enhanced fluorescence (MEF) represents an attractive method for shortening detection times and increasing sensitivity of various fluorescence-based analytical technologies. This review provides an introduction to fundamentals of PEF, illustrates current developments in design of metallic nanostructures for efficient fluorescence signal amplification that utilizes propagating and localized surface plasmons, and summarizes current implementations to biosensors for detection of trace amounts of biomarkers, toxins, and pathogens that are relevant to medical diagnostics and food control.",2014 Dec 28,"['Bauch, Martin', 'Toma, Koji', 'Toma, Mana', 'Zhang, Qingwen', 'Dostalek, Jakub']",Plasmonics,,,True
a0cdda9586848d0b0a9f96b41500531ff2593f05,PMC,2014 ACVIM Forum Research Report Program,http://dx.doi.org/10.1111/jvim.12375,PMC4857940,,NO-CC CODE,,2014 May 19 Jul-Aug,,J Vet Intern Med,,,False
ec36627d378bd763bd34105515a08f6f55f03da1,PMC,Severe Systemic Calciphylaxis in a Young Cat,http://dx.doi.org/10.1111/jvim.12378,PMC4857947,24903891,NO-CC CODE,,2014 Jun 5 Jul-Aug,"['Anfinsen, K.P.', 'Piercy, R.J.', 'Massey, C.', 'Smith, K.C.', 'Kenny, P.J.', 'Garden, O.A.']",J Vet Intern Med,,,True
737c765488563c2864d576b696f16198bc83344c,PMC,Oral Research Communications of the 23rd ECVIM‐CA Congress,http://dx.doi.org/10.1111/jvim.12278,PMC4857967,,NO-CC CODE,,2014 Dec 26 Mar-Apr,,J Vet Intern Med,,,False
0a3a221e70ed8497ac197567fe69e7d384759826,PMC,Disease Associated with Equine Coronavirus Infection and High Case Fatality Rate,http://dx.doi.org/10.1111/jvim.12480,PMC4858071,25319406,NO-CC CODE,"BACKGROUND: Equine coronavirus (ECoV) is associated with clinical disease in adult horses. Outbreaks are associated with a low case fatality rate and a small number of animals with signs of encephalopathic disease are described. OBJECTIVES: The aim of this study is to describe the epidemiological and clinical features of two outbreaks of ECoV infection that were associated with an high case fatality rate. ANIMALS: 14 miniature horses and 1 miniature donkey testing fecal positive for ECoV from two related disease outbreaks. METHODS: Retrospective study describing the epidemiological findings, clinicopathological findings, and fecal viral load from affected horses. RESULTS: In EcoV positive horses, 27% (4/15) of the animals died or were euthanized. Severe hyperammonemia (677 μmol/L, reference range ≤60 μmol/L) was identified in one animal with signs of encephalopathic disease that subsequently died. Fecal viral load (ECoV genome equivalents per gram of feces) was significantly higher in the nonsurvivors compared to animals that survived (P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Equine coronavirus had a higher case fatality rate in this group of miniature horses than previously reported in other outbreaks of varying breeds. Hyperammonemia could contribute to signs of encephalopathic disease, and the fecal viral load might be of prognostic value in affected horses.",2015 Oct 15 Jan-Feb,"['Fielding, C.L.', 'Higgins, J.K.', 'Higgins, J.C.', 'McIntosh, S.', 'Scott, E.', 'Giannitti, F.', 'Mete, A.', 'Pusterla, N.']",J Vet Intern Med,,,True
f9e51b353d1f30a9dfbb30f0661bffa319c041eb,PMC,"Respiratory Pathogens in Québec Dairy Calves and Their Relationship with Clinical Status, Lung Consolidation, and Average Daily Gain",http://dx.doi.org/10.1111/jvim.12531,PMC4858077,25619524,NO-CC CODE,"BACKGROUND: Bovine respiratory disease (BRD) is 1 of the 2 most important causes of morbidity and mortality in dairy calves. Surprisingly, field data are scant concerning the prevalence of respiratory pathogens involved in BRD in preweaned dairy calves, especially in small herds. OBJECTIVES: To identify the main respiratory pathogens isolated from calves in Québec dairy herds with a high incidence of BRD, and to determine if there is an association between the presence of these pathogens and clinical signs of pneumonia, lung consolidation, or average daily gain. ANIMALS: Cross‐sectional study using a convenience sample of 95 preweaned dairy calves from 11 dairy herds. METHODS: At enrollment, calves were weighed, clinically examined, swabbed (nasal and nasopharyngeal), and lung ultrasonography was performed. One month later, all calves were reweighed. RESULTS: Twenty‐two calves had clinical BRD and 49 had ultrasonographic evidence of lung consolidation. Pasteurella multocida, Mannheimia haemolytica, and Histophilus somni were isolated in 54, 17, and 12 calves, respectively. Mycoplasma bovis was identified by PCR testing or culture in 19 calves, and 78 calves were found to be positive for Mycoplasma spp. Bovine coronavirus was detected in 38 calves and bovine respiratory syncytial virus in 1. Only the presence of M. bovis was associated with higher odds of clinical signs, lung consolidation, and lower average daily gain. CONCLUSIONS AND CLINICAL IMPORTANCE: Results suggested that nasopharyngeal carriage of M. bovis was detrimental to health and growth of dairy calves in small herds with a high incidence of BRD.",2015 Jan 25 Jan-Feb,"['Francoz, D.', 'Buczinski, S.', 'Bélanger, A.M.', 'Forté, G.', 'Labrecque, O.', 'Tremblay, D.', 'Wellemans, V.', 'Dubuc, J.']",J Vet Intern Med,,,True
5f2ac6c6a2cdc245be5786c14f13fa75995be36c,PMC,"Outbreak of Middle East Respiratory Syndrome at Tertiary Care Hospital, Jeddah, Saudi Arabia, 2014",http://dx.doi.org/10.3201/eid2205.151797,PMC4861521,27089550,NO-CC CODE,"During March–May 2014, a Middle East respiratory syndrome (MERS) outbreak occurred in Jeddah, Saudi Arabia, that included many persons who worked or received medical treatment at King Fahd General Hospital. We investigated 78 persons who had laboratory-confirmed MERS during March 2–May 10 and documented contact at this hospital. The 78 persons with MERS comprised 53 patients, 16 healthcare workers, and 9 visitors. Among the 53 patients, the most probable sites of acquisition were the emergency department (22 patients), inpatient areas (17), dialysis unit (11), and outpatient areas (3). Infection control deficiencies included limited separation of suspected MERS patients, patient crowding, and inconsistent use of infection control precautions; aggressive improvements in these deficiencies preceded a decline in cases. MERS coronavirus transmission probably was multifocal, occurring in multiple hospital settings. Continued vigilance and strict application of infection control precautions are necessary to prevent future MERS outbreaks.",2016 May,"['Hastings, Deborah L.', 'Tokars, Jerome I.', 'Abdel Aziz, Inas Zakaria A.M.', 'Alkhaldi, Khulud Z.', 'Bensadek, Areej T.', 'Alraddadi, Basem M.', 'Jokhdar, Hani', 'Jernigan, John A.', 'Garout, Mohammed A.', 'Tomczyk, Sara M.', 'Oboho, Ikwo K.', 'Geller, Andrew I.', 'Arinaminpathy, Nimalan', 'Swerdlow, David L.', 'Madani, Tariq A.']",Emerg Infect Dis,,,True
2747330a4eca3fc78e67be4fbf4eb5d127d33e73,PMC,"Outbreak of Middle East Respiratory Syndrome at Tertiary Care Hospital, Jeddah, Saudi Arabia, 2014",http://dx.doi.org/10.3201/eid2205.151797,PMC4861521,27089550,NO-CC CODE,"During March–May 2014, a Middle East respiratory syndrome (MERS) outbreak occurred in Jeddah, Saudi Arabia, that included many persons who worked or received medical treatment at King Fahd General Hospital. We investigated 78 persons who had laboratory-confirmed MERS during March 2–May 10 and documented contact at this hospital. The 78 persons with MERS comprised 53 patients, 16 healthcare workers, and 9 visitors. Among the 53 patients, the most probable sites of acquisition were the emergency department (22 patients), inpatient areas (17), dialysis unit (11), and outpatient areas (3). Infection control deficiencies included limited separation of suspected MERS patients, patient crowding, and inconsistent use of infection control precautions; aggressive improvements in these deficiencies preceded a decline in cases. MERS coronavirus transmission probably was multifocal, occurring in multiple hospital settings. Continued vigilance and strict application of infection control precautions are necessary to prevent future MERS outbreaks.",2016 May,"['Hastings, Deborah L.', 'Tokars, Jerome I.', 'Abdel Aziz, Inas Zakaria A.M.', 'Alkhaldi, Khulud Z.', 'Bensadek, Areej T.', 'Alraddadi, Basem M.', 'Jokhdar, Hani', 'Jernigan, John A.', 'Garout, Mohammed A.', 'Tomczyk, Sara M.', 'Oboho, Ikwo K.', 'Geller, Andrew I.', 'Arinaminpathy, Nimalan', 'Swerdlow, David L.', 'Madani, Tariq A.']",Emerg Infect Dis,,,True
c723a1d259891519fd489b94a7ff128f9a5555aa,PMC,Partitioning of Viruses in Wastewater Systems and Potential for Aerosolization,http://dx.doi.org/10.1021/acs.estlett.6b00105,PMC4869619,27213164,NO-CC CODE,"[Image: see text] To gain insight into the potential for aerosolization of viruses in wastewater systems, we investigated the partitioning of MS2 and Phi6 bacteriophages in synthetic sludge and anaerobically digested sludge from a wastewater treatment plant. We evaluated partitioning among the liquid, solids, and material surfaces of porcelain, concrete, polyvinyl chloride (PVC), and polypropylene. In all cases, at least 94% of the virions partitioned into the liquid fraction. In real sludge, no more than 0.8% of virions partitioned to the solids and no more than 6% to the material surface. Both MS2 and Phi6 partitioned more to the surface of concrete and polypropylene than to the surface of porcelain or PVC. Partitioning of viruses in wastewater among the liquid, biosolids, and material surface does not appear to mitigate the potential for aerosolization of virus, as most of the virus remains in the liquid phase.",2016 May 10,"['Titcombe Lee, Mari', 'Pruden, Amy', 'Marr, Linsey C.']",Environ Sci Technol Lett,,,True
fed59469020955a3f7dfe77ab7c593643d48f505,PMC,Partitioning of Viruses in Wastewater Systems and Potential for Aerosolization,http://dx.doi.org/10.1021/acs.estlett.6b00105,PMC4869619,27213164,NO-CC CODE,"[Image: see text] To gain insight into the potential for aerosolization of viruses in wastewater systems, we investigated the partitioning of MS2 and Phi6 bacteriophages in synthetic sludge and anaerobically digested sludge from a wastewater treatment plant. We evaluated partitioning among the liquid, solids, and material surfaces of porcelain, concrete, polyvinyl chloride (PVC), and polypropylene. In all cases, at least 94% of the virions partitioned into the liquid fraction. In real sludge, no more than 0.8% of virions partitioned to the solids and no more than 6% to the material surface. Both MS2 and Phi6 partitioned more to the surface of concrete and polypropylene than to the surface of porcelain or PVC. Partitioning of viruses in wastewater among the liquid, biosolids, and material surface does not appear to mitigate the potential for aerosolization of virus, as most of the virus remains in the liquid phase.",2016 May 10,"['Titcombe Lee, Mari', 'Pruden, Amy', 'Marr, Linsey C.']",Environ Sci Technol Lett,,,True
18d51b527546f388651b7d1322d9a9538c333b61,PMC,A LAIR-1 insertion generates broadly reactive antibodies against malaria variant antigens,http://dx.doi.org/10.1038/nature16450,PMC4869849,26700814,NO-CC CODE,"Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies(1–4). Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here, we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 100 amino acid collagen-binding domain of LAIR-1, an Ig superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B cell clone and carry distinct somatic mutations in the LAIR-1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine.",2016 Jan 7,"['Tan, Joshua', 'Pieper, Kathrin', 'Piccoli, Luca', 'Abdi, Abdirahman', 'Perez, Mathilde Foglierini', 'Geiger, Roger', 'Tully, Claire Maria', 'Jarrossay, David', 'Maina Ndungu, Francis', 'Wambua, Juliana', 'Bejon, Philip', 'Fregni, Chiara Silacci', 'Fernandez-Rodriguez, Blanca', 'Barbieri, Sonia', 'Bianchi, Siro', 'Marsh, Kevin', 'Thathy, Vandana', 'Corti, Davide', 'Sallusto, Federica', 'Bull, Peter', 'Lanzavecchia, Antonio']",Nature,,,True
12402a4aed4db76e2fa3f0d7c7169c18478c44f5,PMC,A LAIR-1 insertion generates broadly reactive antibodies against malaria variant antigens,http://dx.doi.org/10.1038/nature16450,PMC4869849,26700814,NO-CC CODE,"Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies(1–4). Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here, we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 100 amino acid collagen-binding domain of LAIR-1, an Ig superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B cell clone and carry distinct somatic mutations in the LAIR-1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine.",2016 Jan 7,"['Tan, Joshua', 'Pieper, Kathrin', 'Piccoli, Luca', 'Abdi, Abdirahman', 'Perez, Mathilde Foglierini', 'Geiger, Roger', 'Tully, Claire Maria', 'Jarrossay, David', 'Maina Ndungu, Francis', 'Wambua, Juliana', 'Bejon, Philip', 'Fregni, Chiara Silacci', 'Fernandez-Rodriguez, Blanca', 'Barbieri, Sonia', 'Bianchi, Siro', 'Marsh, Kevin', 'Thathy, Vandana', 'Corti, Davide', 'Sallusto, Federica', 'Bull, Peter', 'Lanzavecchia, Antonio']",Nature,,,False
94b25ecf44f04f66625ca9975f07118df3a0033f,PMC,A LAIR-1 insertion generates broadly reactive antibodies against malaria variant antigens,http://dx.doi.org/10.1038/nature16450,PMC4869849,26700814,NO-CC CODE,"Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies(1–4). Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here, we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 100 amino acid collagen-binding domain of LAIR-1, an Ig superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B cell clone and carry distinct somatic mutations in the LAIR-1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine.",2016 Jan 7,"['Tan, Joshua', 'Pieper, Kathrin', 'Piccoli, Luca', 'Abdi, Abdirahman', 'Perez, Mathilde Foglierini', 'Geiger, Roger', 'Tully, Claire Maria', 'Jarrossay, David', 'Maina Ndungu, Francis', 'Wambua, Juliana', 'Bejon, Philip', 'Fregni, Chiara Silacci', 'Fernandez-Rodriguez, Blanca', 'Barbieri, Sonia', 'Bianchi, Siro', 'Marsh, Kevin', 'Thathy, Vandana', 'Corti, Davide', 'Sallusto, Federica', 'Bull, Peter', 'Lanzavecchia, Antonio']",Nature,,,False
b6b5b7639a890decf17cb745a6551bb3cf8f7b1e,PMC,A LAIR-1 insertion generates broadly reactive antibodies against malaria variant antigens,http://dx.doi.org/10.1038/nature16450,PMC4869849,26700814,NO-CC CODE,"Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies(1–4). Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here, we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 100 amino acid collagen-binding domain of LAIR-1, an Ig superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B cell clone and carry distinct somatic mutations in the LAIR-1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine.",2016 Jan 7,"['Tan, Joshua', 'Pieper, Kathrin', 'Piccoli, Luca', 'Abdi, Abdirahman', 'Perez, Mathilde Foglierini', 'Geiger, Roger', 'Tully, Claire Maria', 'Jarrossay, David', 'Maina Ndungu, Francis', 'Wambua, Juliana', 'Bejon, Philip', 'Fregni, Chiara Silacci', 'Fernandez-Rodriguez, Blanca', 'Barbieri, Sonia', 'Bianchi, Siro', 'Marsh, Kevin', 'Thathy, Vandana', 'Corti, Davide', 'Sallusto, Federica', 'Bull, Peter', 'Lanzavecchia, Antonio']",Nature,,,False
998602bfbdddd5d3279bc40b458e4706f4ca81da,PMC,A LAIR-1 insertion generates broadly reactive antibodies against malaria variant antigens,http://dx.doi.org/10.1038/nature16450,PMC4869849,26700814,NO-CC CODE,"Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies(1–4). Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here, we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 100 amino acid collagen-binding domain of LAIR-1, an Ig superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B cell clone and carry distinct somatic mutations in the LAIR-1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine.",2016 Jan 7,"['Tan, Joshua', 'Pieper, Kathrin', 'Piccoli, Luca', 'Abdi, Abdirahman', 'Perez, Mathilde Foglierini', 'Geiger, Roger', 'Tully, Claire Maria', 'Jarrossay, David', 'Maina Ndungu, Francis', 'Wambua, Juliana', 'Bejon, Philip', 'Fregni, Chiara Silacci', 'Fernandez-Rodriguez, Blanca', 'Barbieri, Sonia', 'Bianchi, Siro', 'Marsh, Kevin', 'Thathy, Vandana', 'Corti, Davide', 'Sallusto, Federica', 'Bull, Peter', 'Lanzavecchia, Antonio']",Nature,,,False
b0ad202646441ca3d86a08a65f4b1c0ad90b43ab,PMC,A LAIR-1 insertion generates broadly reactive antibodies against malaria variant antigens,http://dx.doi.org/10.1038/nature16450,PMC4869849,26700814,NO-CC CODE,"Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies(1–4). Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here, we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 100 amino acid collagen-binding domain of LAIR-1, an Ig superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B cell clone and carry distinct somatic mutations in the LAIR-1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine.",2016 Jan 7,"['Tan, Joshua', 'Pieper, Kathrin', 'Piccoli, Luca', 'Abdi, Abdirahman', 'Perez, Mathilde Foglierini', 'Geiger, Roger', 'Tully, Claire Maria', 'Jarrossay, David', 'Maina Ndungu, Francis', 'Wambua, Juliana', 'Bejon, Philip', 'Fregni, Chiara Silacci', 'Fernandez-Rodriguez, Blanca', 'Barbieri, Sonia', 'Bianchi, Siro', 'Marsh, Kevin', 'Thathy, Vandana', 'Corti, Davide', 'Sallusto, Federica', 'Bull, Peter', 'Lanzavecchia, Antonio']",Nature,,,False
528793e51b7aa9012d0e7a9ea4a6030ff3f3c818,PMC,A LAIR-1 insertion generates broadly reactive antibodies against malaria variant antigens,http://dx.doi.org/10.1038/nature16450,PMC4869849,26700814,NO-CC CODE,"Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies(1–4). Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here, we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 100 amino acid collagen-binding domain of LAIR-1, an Ig superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B cell clone and carry distinct somatic mutations in the LAIR-1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine.",2016 Jan 7,"['Tan, Joshua', 'Pieper, Kathrin', 'Piccoli, Luca', 'Abdi, Abdirahman', 'Perez, Mathilde Foglierini', 'Geiger, Roger', 'Tully, Claire Maria', 'Jarrossay, David', 'Maina Ndungu, Francis', 'Wambua, Juliana', 'Bejon, Philip', 'Fregni, Chiara Silacci', 'Fernandez-Rodriguez, Blanca', 'Barbieri, Sonia', 'Bianchi, Siro', 'Marsh, Kevin', 'Thathy, Vandana', 'Corti, Davide', 'Sallusto, Federica', 'Bull, Peter', 'Lanzavecchia, Antonio']",Nature,,,False
a42c9a22f00973b3505bf87c0edba9327fe1f4c5,PMC,A LAIR-1 insertion generates broadly reactive antibodies against malaria variant antigens,http://dx.doi.org/10.1038/nature16450,PMC4869849,26700814,NO-CC CODE,"Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies(1–4). Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here, we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 100 amino acid collagen-binding domain of LAIR-1, an Ig superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B cell clone and carry distinct somatic mutations in the LAIR-1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine.",2016 Jan 7,"['Tan, Joshua', 'Pieper, Kathrin', 'Piccoli, Luca', 'Abdi, Abdirahman', 'Perez, Mathilde Foglierini', 'Geiger, Roger', 'Tully, Claire Maria', 'Jarrossay, David', 'Maina Ndungu, Francis', 'Wambua, Juliana', 'Bejon, Philip', 'Fregni, Chiara Silacci', 'Fernandez-Rodriguez, Blanca', 'Barbieri, Sonia', 'Bianchi, Siro', 'Marsh, Kevin', 'Thathy, Vandana', 'Corti, Davide', 'Sallusto, Federica', 'Bull, Peter', 'Lanzavecchia, Antonio']",Nature,,,False
2eee02ecee419e86eb6511fa1f8dc603e90761af,PMC,A LAIR-1 insertion generates broadly reactive antibodies against malaria variant antigens,http://dx.doi.org/10.1038/nature16450,PMC4869849,26700814,NO-CC CODE,"Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies(1–4). Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here, we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 100 amino acid collagen-binding domain of LAIR-1, an Ig superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B cell clone and carry distinct somatic mutations in the LAIR-1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine.",2016 Jan 7,"['Tan, Joshua', 'Pieper, Kathrin', 'Piccoli, Luca', 'Abdi, Abdirahman', 'Perez, Mathilde Foglierini', 'Geiger, Roger', 'Tully, Claire Maria', 'Jarrossay, David', 'Maina Ndungu, Francis', 'Wambua, Juliana', 'Bejon, Philip', 'Fregni, Chiara Silacci', 'Fernandez-Rodriguez, Blanca', 'Barbieri, Sonia', 'Bianchi, Siro', 'Marsh, Kevin', 'Thathy, Vandana', 'Corti, Davide', 'Sallusto, Federica', 'Bull, Peter', 'Lanzavecchia, Antonio']",Nature,,,False
c2a4acfef3152ab6cdab7b6bd5937e9237b0f907,PMC,A LAIR-1 insertion generates broadly reactive antibodies against malaria variant antigens,http://dx.doi.org/10.1038/nature16450,PMC4869849,26700814,NO-CC CODE,"Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies(1–4). Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here, we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 100 amino acid collagen-binding domain of LAIR-1, an Ig superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B cell clone and carry distinct somatic mutations in the LAIR-1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine.",2016 Jan 7,"['Tan, Joshua', 'Pieper, Kathrin', 'Piccoli, Luca', 'Abdi, Abdirahman', 'Perez, Mathilde Foglierini', 'Geiger, Roger', 'Tully, Claire Maria', 'Jarrossay, David', 'Maina Ndungu, Francis', 'Wambua, Juliana', 'Bejon, Philip', 'Fregni, Chiara Silacci', 'Fernandez-Rodriguez, Blanca', 'Barbieri, Sonia', 'Bianchi, Siro', 'Marsh, Kevin', 'Thathy, Vandana', 'Corti, Davide', 'Sallusto, Federica', 'Bull, Peter', 'Lanzavecchia, Antonio']",Nature,,,False
a9b1663a4cf6ace92b7aafb3af1541b9e402c09b,PMC,A LAIR-1 insertion generates broadly reactive antibodies against malaria variant antigens,http://dx.doi.org/10.1038/nature16450,PMC4869849,26700814,NO-CC CODE,"Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies(1–4). Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here, we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 100 amino acid collagen-binding domain of LAIR-1, an Ig superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B cell clone and carry distinct somatic mutations in the LAIR-1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine.",2016 Jan 7,"['Tan, Joshua', 'Pieper, Kathrin', 'Piccoli, Luca', 'Abdi, Abdirahman', 'Perez, Mathilde Foglierini', 'Geiger, Roger', 'Tully, Claire Maria', 'Jarrossay, David', 'Maina Ndungu, Francis', 'Wambua, Juliana', 'Bejon, Philip', 'Fregni, Chiara Silacci', 'Fernandez-Rodriguez, Blanca', 'Barbieri, Sonia', 'Bianchi, Siro', 'Marsh, Kevin', 'Thathy, Vandana', 'Corti, Davide', 'Sallusto, Federica', 'Bull, Peter', 'Lanzavecchia, Antonio']",Nature,,,False
5ab16b965a04942b212bf4508e96f2667f63a1d5,PMC,A LAIR-1 insertion generates broadly reactive antibodies against malaria variant antigens,http://dx.doi.org/10.1038/nature16450,PMC4869849,26700814,NO-CC CODE,"Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies(1–4). Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here, we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 100 amino acid collagen-binding domain of LAIR-1, an Ig superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B cell clone and carry distinct somatic mutations in the LAIR-1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine.",2016 Jan 7,"['Tan, Joshua', 'Pieper, Kathrin', 'Piccoli, Luca', 'Abdi, Abdirahman', 'Perez, Mathilde Foglierini', 'Geiger, Roger', 'Tully, Claire Maria', 'Jarrossay, David', 'Maina Ndungu, Francis', 'Wambua, Juliana', 'Bejon, Philip', 'Fregni, Chiara Silacci', 'Fernandez-Rodriguez, Blanca', 'Barbieri, Sonia', 'Bianchi, Siro', 'Marsh, Kevin', 'Thathy, Vandana', 'Corti, Davide', 'Sallusto, Federica', 'Bull, Peter', 'Lanzavecchia, Antonio']",Nature,,,False
ce92831247b14a53f4b0d08a494c8458ea34de50,PMC,A LAIR-1 insertion generates broadly reactive antibodies against malaria variant antigens,http://dx.doi.org/10.1038/nature16450,PMC4869849,26700814,NO-CC CODE,"Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies(1–4). Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here, we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 100 amino acid collagen-binding domain of LAIR-1, an Ig superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B cell clone and carry distinct somatic mutations in the LAIR-1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine.",2016 Jan 7,"['Tan, Joshua', 'Pieper, Kathrin', 'Piccoli, Luca', 'Abdi, Abdirahman', 'Perez, Mathilde Foglierini', 'Geiger, Roger', 'Tully, Claire Maria', 'Jarrossay, David', 'Maina Ndungu, Francis', 'Wambua, Juliana', 'Bejon, Philip', 'Fregni, Chiara Silacci', 'Fernandez-Rodriguez, Blanca', 'Barbieri, Sonia', 'Bianchi, Siro', 'Marsh, Kevin', 'Thathy, Vandana', 'Corti, Davide', 'Sallusto, Federica', 'Bull, Peter', 'Lanzavecchia, Antonio']",Nature,,,False
d8932d954c612d2ef0220a53943c24e7b0920dac,PMC,Respiratory source control using a surgical mask: An in vitro study,http://dx.doi.org/10.1080/15459624.2015.1043050,PMC4873718,26225807,NO-CC CODE,"Cough etiquette and respiratory hygiene are forms of source control encouraged to prevent the spread of respiratory infection. The use of surgical masks as a means of source control has not been quantified in terms of reducing exposure to others. We designed an in vitro model using various facepieces to assess their contribution to exposure reduction when worn at the infectious source (Source) relative to facepieces worn for primary (Receiver) protection, and the factors that contribute to each. In a chamber with various airflows, radiolabeled aerosols were exhaled via a ventilated soft-face manikin head using tidal breathing and cough (Source). Another manikin, containing a filter, quantified recipient exposure (Receiver). The natural fit surgical mask, fitted (SecureFit) surgical mask and an N95-class filtering facepiece respirator (commonly known as an “N95 respirator”) with and without a Vaseline-seal were tested. With cough, source control (mask or respirator on Source) was statistically superior to mask or unsealed respirator protection on the Receiver (Receiver protection) in all environments. To equal source control during coughing, the N95 respirator must be Vaseline-sealed. During tidal breathing, source control was comparable or superior to mask or respirator protection on the Receiver. Source control via surgical masks may be an important adjunct defense against the spread of respiratory infections. The fit of the mask or respirator, in combination with the airflow patterns in a given setting, are significant contributors to source control efficacy. Future clinical trials should include a surgical mask source control arm to assess the contribution of source control in overall protection against airborne infection.",2016 Jul 2,"['Patel, Rajeev B.', 'Skaria, Shaji D.', 'Mansour, Mohamed M.', 'Smaldone, Gerald C.']",J Occup Environ Hyg,,,True
e4514865ab32606bac0018ad579fe143067874bd,PMC,"Population-Level Effect of Cholera Vaccine on Displaced Populations, South Sudan, 2014",http://dx.doi.org/10.3201/eid2206.151592,PMC4880069,27192187,NO-CC CODE,"Following mass population displacements in South Sudan, preventive cholera vaccination campaigns were conducted in displaced persons camps before a 2014 cholera outbreak. We compare cholera transmission in vaccinated and unvaccinated areas and show vaccination likely halted transmission within vaccinated areas, illustrating the potential for oral cholera vaccine to stop cholera transmission in vulnerable populations.",2016 Jun,"['Azman, Andrew S.', 'Rumunu, John', 'Abubakar, Abdinasir', 'West, Haley', 'Ciglenecki, Iza', 'Helderman, Trina', 'Wamala, Joseph Francis', 'Vázquez, Olimpia de la Rosa', 'Perea, William', 'Sack, David A.', 'Legros, Dominique', 'Martin, Stephen', 'Lessler, Justin', 'Luquero, Francisco J.']",Emerg Infect Dis,,,True
4d073b45fadd07706636593f9c9aee196536eaf3,PMC,"Population-Level Effect of Cholera Vaccine on Displaced Populations, South Sudan, 2014",http://dx.doi.org/10.3201/eid2206.151592,PMC4880069,27192187,NO-CC CODE,"Following mass population displacements in South Sudan, preventive cholera vaccination campaigns were conducted in displaced persons camps before a 2014 cholera outbreak. We compare cholera transmission in vaccinated and unvaccinated areas and show vaccination likely halted transmission within vaccinated areas, illustrating the potential for oral cholera vaccine to stop cholera transmission in vulnerable populations.",2016 Jun,"['Azman, Andrew S.', 'Rumunu, John', 'Abubakar, Abdinasir', 'West, Haley', 'Ciglenecki, Iza', 'Helderman, Trina', 'Wamala, Joseph Francis', 'Vázquez, Olimpia de la Rosa', 'Perea, William', 'Sack, David A.', 'Legros, Dominique', 'Martin, Stephen', 'Lessler, Justin', 'Luquero, Francisco J.']",Emerg Infect Dis,,,True
b8c816b6461d1c8bf4603f85f6e9841c172a8bc1,PMC,"Infection, Replication, and Transmission of Middle East Respiratory Syndrome Coronavirus in Alpacas",http://dx.doi.org/10.3201/eid2206.160192,PMC4880070,27070385,NO-CC CODE,"Middle East respiratory syndrome coronavirus is a recently emerged pathogen associated with severe human disease. Zoonotic spillover from camels appears to play a major role in transmission. Because of logistic difficulties in working with dromedaries in containment, a more manageable animal model would be desirable. We report shedding and transmission of this virus in experimentally infected alpacas (n = 3) or those infected by contact (n = 3). Infectious virus was detected in all infected animals and in 2 of 3 in-contact animals. All alpacas seroconverted and were rechallenged 70 days after the original infection. Experimentally infected animals were protected against reinfection, and those infected by contact were partially protected. Necropsy specimens from immunologically naive animals (n = 3) obtained on day 5 postinfection showed virus in the upper respiratory tract. These data demonstrate efficient virus replication and animal-to-animal transmission and indicate that alpacas might be useful surrogates for camels in laboratory studies.",2016 Jun,"['Adney, Danielle R.', 'Bielefeldt-Ohmann, Helle', 'Hartwig, Airn E.', 'Bowen, Richard A.']",Emerg Infect Dis,,,True
d80a7090ab5c8141c7dbedb3b8bf302b1bdcee40,PMC,MERS-CoV Infection of Alpaca in a Region Where MERS-CoV is Endemic,http://dx.doi.org/10.3201/eid2206.152113,PMC4880085,27070501,NO-CC CODE,,2016 Jun,"['Reusken, Chantal B.E.M.', 'Schilp, Chrispijn', 'Raj, V. Stalin', 'De Bruin, Erwin', 'Kohl, Robert H.G.', 'Farag, Elmoubasher A.B.A.', 'Haagmans, Bart L.', 'Al-Romaihi, Hamad', 'Le Grange, Francois', 'Bosch, Berend-Jan', 'Koopmans, Marion P.G.']",Emerg Infect Dis,,,True
191e007b37a6d065812478b235a03ec1ebb0202f,PMC,MERS-CoV Infection of Alpaca in a Region Where MERS-CoV is Endemic,http://dx.doi.org/10.3201/eid2206.152113,PMC4880085,27070501,NO-CC CODE,,2016 Jun,"['Reusken, Chantal B.E.M.', 'Schilp, Chrispijn', 'Raj, V. Stalin', 'De Bruin, Erwin', 'Kohl, Robert H.G.', 'Farag, Elmoubasher A.B.A.', 'Haagmans, Bart L.', 'Al-Romaihi, Hamad', 'Le Grange, Francois', 'Bosch, Berend-Jan', 'Koopmans, Marion P.G.']",Emerg Infect Dis,,,True
1dba435e932ac0171832c22334dff3a382a0ad14,PMC,"MERS-CoV Antibodies in Humans, Africa, 2013–2014",http://dx.doi.org/10.3201/eid2206.160064,PMC4880087,27071076,NO-CC CODE,"Dromedaries in Africa and elsewhere carry the Middle East respiratory syndrome coronavirus (MERS-CoV). To search for evidence of autochthonous MERS-CoV infection in humans, we tested archived serum from livestock handlers in Kenya for MERS-CoV antibodies. Serologic evidence of infection was confirmed for 2 persons sampled in 2013 and 2014.",2016 Jun,"['Liljander, Anne', 'Meyer, Benjamin', 'Jores, Joerg', 'Müller, Marcel A.', 'Lattwein, Erik', 'Njeru, Ian', 'Bett, Bernard', 'Drosten, Christian', 'Corman, Victor Max']",Emerg Infect Dis,,,True
b14030110db9acc99c663c87643a6754ab25b6d8,PMC,"MERS-CoV Antibodies in Humans, Africa, 2013–2014",http://dx.doi.org/10.3201/eid2206.160064,PMC4880087,27071076,NO-CC CODE,"Dromedaries in Africa and elsewhere carry the Middle East respiratory syndrome coronavirus (MERS-CoV). To search for evidence of autochthonous MERS-CoV infection in humans, we tested archived serum from livestock handlers in Kenya for MERS-CoV antibodies. Serologic evidence of infection was confirmed for 2 persons sampled in 2013 and 2014.",2016 Jun,"['Liljander, Anne', 'Meyer, Benjamin', 'Jores, Joerg', 'Müller, Marcel A.', 'Lattwein, Erik', 'Njeru, Ian', 'Bett, Bernard', 'Drosten, Christian', 'Corman, Victor Max']",Emerg Infect Dis,,,True
5caf51a982d8b7e59cb54b2eb532f1eb43fe8a63,PMC,Perspective and Surprise in the Floating World,http://dx.doi.org/10.3201/eid2206.AC2206,PMC4880092,,NO-CC CODE,,2016 Jun,"['Breedlove, Byron', 'Friedberg, Jared']",Emerg Infect Dis,,,True
afb0a74705b6788ca4c0f9a1dc056200000d7f0f,PMC,Antibody Response and Disease Severity in Healthcare Worker MERS Survivors,http://dx.doi.org/10.3201/eid2206.160010,PMC4880093,27192543,NO-CC CODE,"We studied antibody response in 9 healthcare workers in Jeddah, Saudi Arabia, who survived Middle East respiratory syndrome, by using serial ELISA and indirect immunofluorescence assay testing. Among patients who had experienced severe pneumonia, antibody was detected for >18 months after infection. Antibody longevity was more variable in patients who had experienced milder disease.",2016 Jun,"['Alshukairi, Abeer N.', 'Khalid, Imran', 'Ahmed, Waleed A.', 'Dada, Ashraf M.', 'Bayumi, Daniyah T.', 'Malic, Laut S.', 'Althawadi, Sahar', 'Ignacio, Kim', 'Alsalmi, Hanadi S.', 'Al-Abdely, Hail M.', 'Wali, Ghassan Y.', 'Qushmaq, Ismael A.', 'Alraddadi, Basem M.', 'Perlman, Stanley']",Emerg Infect Dis,,,True
8fe8deec61edda35cbb08de93a02c9930c32a1eb,PMC,Antibody Response and Disease Severity in Healthcare Worker MERS Survivors,http://dx.doi.org/10.3201/eid2206.160010,PMC4880093,27192543,NO-CC CODE,"We studied antibody response in 9 healthcare workers in Jeddah, Saudi Arabia, who survived Middle East respiratory syndrome, by using serial ELISA and indirect immunofluorescence assay testing. Among patients who had experienced severe pneumonia, antibody was detected for >18 months after infection. Antibody longevity was more variable in patients who had experienced milder disease.",2016 Jun,"['Alshukairi, Abeer N.', 'Khalid, Imran', 'Ahmed, Waleed A.', 'Dada, Ashraf M.', 'Bayumi, Daniyah T.', 'Malic, Laut S.', 'Althawadi, Sahar', 'Ignacio, Kim', 'Alsalmi, Hanadi S.', 'Al-Abdely, Hail M.', 'Wali, Ghassan Y.', 'Qushmaq, Ismael A.', 'Alraddadi, Basem M.', 'Perlman, Stanley']",Emerg Infect Dis,,,True
a21078272350d16ee144e2c00faf0d68de89152d,PMC,Improved Global Capacity for Influenza Surveillance,http://dx.doi.org/10.3201/eid2206.151521,PMC4880096,27192395,NO-CC CODE,"During 2004–2009, the Centers for Disease Control and Prevention (CDC) partnered with 39 national governments to strengthen global influenza surveillance. Using World Health Organization data and program evaluation indicators collected by CDC in 2013, we retrospectively evaluated progress made 4–9 years after the start of influenza surveillance capacity strengthening in the countries. Our results showed substantial increases in laboratory and sentinel surveillance capacities, which are essential for knowing which influenza strains circulate globally, detecting emergence of novel influenza, identifying viruses for vaccine selection, and determining the epidemiology of respiratory illness. Twenty-eight of 35 countries responding to a 2013 questionnaire indicated that they have leveraged routine influenza surveillance platforms to detect other pathogens. This additional surveillance illustrates increased health-system strengthening. Furthermore, 34 countries reported an increased ability to use data in decision making; data-driven decisions are critical for improving local prevention and control of influenza around the world.",2016 Jun,"['Polansky, Lauren S.', 'Outin-Blenman, Sajata', 'Moen, Ann C.']",Emerg Infect Dis,,,True
c5fa97f3c08e5b88b1081d261c675cf9f0fea73b,PMC,Experimental Infection and Response to Rechallenge of Alpacas with Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.3201/eid2206.160007,PMC4880109,27070733,NO-CC CODE,We conducted a challenge/rechallenge trial in which 3 alpacas were infected with Middle East respiratory syndrome coronavirus. The alpacas shed virus at challenge but were refractory to further shedding at rechallenge on day 21. The trial indicates that alpacas may be suitable models for infection and shedding dynamics of this virus.,2016 Jun,"['Crameri, Gary', 'Durr, Peter A.', 'Klein, Reuben', 'Foord, Adam', 'Yu, Meng', 'Riddell, Sarah', 'Haining, Jessica', 'Johnson, Dayna', 'Hemida, Maged G.', 'Barr, Jennifer', 'Peiris, Malik', 'Middleton, Deborah', 'Wang, Lin-Fa']",Emerg Infect Dis,,,True
81c58ed877196e83b07a5f5450999bdf06a5be1e,PMC,Experimental Infection and Response to Rechallenge of Alpacas with Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.3201/eid2206.160007,PMC4880109,27070733,NO-CC CODE,We conducted a challenge/rechallenge trial in which 3 alpacas were infected with Middle East respiratory syndrome coronavirus. The alpacas shed virus at challenge but were refractory to further shedding at rechallenge on day 21. The trial indicates that alpacas may be suitable models for infection and shedding dynamics of this virus.,2016 Jun,"['Crameri, Gary', 'Durr, Peter A.', 'Klein, Reuben', 'Foord, Adam', 'Yu, Meng', 'Riddell, Sarah', 'Haining, Jessica', 'Johnson, Dayna', 'Hemida, Maged G.', 'Barr, Jennifer', 'Peiris, Malik', 'Middleton, Deborah', 'Wang, Lin-Fa']",Emerg Infect Dis,,,False
ffe133ed880d6c77ae340c5374817232e21f8315,PMC,Rational Design of Peptide Vaccines Against Multiple Types of Human Papillomavirus,http://dx.doi.org/10.4137/CIN.S39071,PMC4890726,27279731,NO-CC CODE,"Human papillomavirus (HPV) occurs in many types, some of which cause cervical, genital, and other cancers. While vaccination is available against the major cancer-causing HPV types, many others are not covered by these preventive measures. Herein, we present a bioinformatics study for the designing of multivalent peptide vaccines against multiple HPV types as an alternative strategy to the virus-like particle vaccines being used now. Our technique of rational design of peptide vaccines is expected to ensure stability of the vaccine against many cycles of mutational changes, elicit immune response, and negate autoimmune possibilities. Using the L1 capsid protein sequences, we identified several peptides for potential vaccine design for HPV 16, 18, 33, 35, 45, and 11 types. Although there are concerns about the epitope-binding affinities for the peptides identified in this process, the technique indicates possibilities of multivalent, adjuvanted, peptide vaccines against a wider range of HPV types, and tailor-made different combinations of the peptides to address frequency variations of types over different population groups as required for prophylaxis and at lower cost than are in use at the present time.",2016 Jun 1,"['Dey, Sumanta', 'De, Antara', 'Nandy, Ashesh']",Cancer Inform,,,True
6c9503d198ff881915e3ea30dd52435740b70bfa,PMC,Proceedings 26th Symposium ESVN‐ECVN,http://dx.doi.org/10.1111/jvim.12323,PMC4895466,,NO-CC CODE,,2014 Mar 1 May-Jun,,J Vet Intern Med,,,False
57145f9607b426eace5798c4045716ab6e3af5ff,PMC,Passive Immunity Stimulated by Vaccination of Dry Cows with a Salmonella Bacterial Extract,http://dx.doi.org/10.1111/jvim.12396,PMC4895567,24986262,NO-CC CODE,"BACKGROUND: Diarrhea because of Salmonella infection is a cause of neonatal calf diarrhea. The stimulation of passive immunity in the calf by vaccinating the dam for Salmonella has shown some success in previous studies; however, there are no data on the use of currently licensed vaccines in the United States. OBJECTIVE: To determine whether vaccinating cows at dry‐off with a commercially available Salmonella bacterial extract would stimulate Salmonella‐specific antibodies in the colostrum of cows at calving and whether these antibodies would be transferred to the calf. ANIMALS: Sixty Holstein cattle and 59 calves from a herd presumed to be naïve to Salmonella. METHODS: Prospective clinical trial. Thirty cows were vaccinated at dry‐off with a Salmonella enterica serovar Newport bacterial extract and again 4 weeks later. An additional 30 cows received only saline. Calves fed fresh colostrum from their dam within 4 hours of birth had blood collected 24 hours later. RESULTS: Vaccinated cattle had increased Salmonella Newport antibody titers at calving in blood (P = .01) and colostrum (P = .011). Calves that received colostrum from vaccinated cattle also had significant increase in Salmonella antibodies (1.04 ± 0.03) as compared to calves born to unvaccinated cows (0.30 ± 0.02). CONCLUSIONS AND CLINICAL IMPORTANCE: The results indicate that the use of a commercially available Salmonella vaccine can stimulate antibodies that are passed on to the calf via colostral transfer. Further studies need to be done to determine whether these antibodies will offer protection against Salmonella challenge.",2014 Jul 1 Sep-Oct,"['Smith, G.W.', 'Alley, M.L.', 'Foster, D.M.', 'Smith, F.', 'Wileman, B.W.']",J Vet Intern Med,,,True
53abe67758ae950feb6f7ee22501a345f597e98b,PMC,Probiotic Use in Horses – What is the Evidence for Their Clinical Efficacy?,http://dx.doi.org/10.1111/jvim.12451,PMC4895607,25231539,NO-CC CODE,"The gastrointestinal microbiota is extremely important for human and animal health. Investigations into the composition of the microbiota and its therapeutic modification have received increasing interest in human and veterinary medicine. Probiotics are a way of modifying the microbiota and have been tested to prevent and treat diseases. Probiotics are proposed to exert their beneficial effects through various pathways. Production of antimicrobial compounds targeting intestinal pathogens, general immune stimulation, and colonization resistance are among these mechanisms. Despite widespread availability and use, scientific, peer‐reviewed evidence behind commercial probiotic formulations in horses is limited. Additionally, quality control of commercial over‐the‐counter products is not tightly regulated. Although promising in vitro results have been achieved, in vivo health benefits have been more difficult to prove. Whether the ambiguous results are caused by strain selection, dosage selection or true lack of efficacy remains to be answered. Although these limitations exist, probiotics are increasingly used because of their lack of severe adverse effects, ease of administration, and low cost. This review summarizes the current evidence for probiotic use in equine medicine. It aims to provide veterinarians with evidence‐based information on when and why probiotics are indicated for prevention or treatment of gastrointestinal disease in horses. The review also outlines the current state of knowledge on the equine microbiota and the potential of fecal microbial transplantation, as they relate to the topic of probiotics.",2014 Sep 17 Nov-Dec,"['Schoster, A.', 'Weese, J.S.', 'Guardabassi, L.']",J Vet Intern Med,,,True
32b34236bf241a4818cf5763dcc46b92be097e16,PMC,Spatiotemporal Interplay of Severe Acute Respiratory Syndrome Coronavirus and Respiratory Mucosal Cells Drives Viral Dissemination in Rhesus Macaques,http://dx.doi.org/10.1038/mi.2015.127,PMC4900951,26647718,NO-CC CODE,"Innate immune responses play a critical role in the control of early virus replication and dissemination. It remains unknown, however, how SARS-CoV evades respiratory innate immunity to establish a systemic infection. Here, we show in Chinese macaques that SARS-CoV traversed the mucosa through the respiratory tract within 2 days, resulting in extensive mucosal infiltration by T cells, MAC387(+) and CD163(+) monocytes/macrophages followed by limited viral replication in the lung but persistent viral shedding into the upper airway. Mucosal monocytes/macrophages sequestered virions in intracellular vesicles together with infected Langerhans cells (LCs) and migrated into the tonsils and/or draining lymph nodes (LNs) within 2 days. In lymphoid tissues, viral RNA and proteins were detected in infected monocytes upon differentiation into dendritic cells (DCs) within 3 days. Systemic viral dissemination was observed within 7 days. This study provides a comprehensive overview of the spatiotemporal interactions of SARS-CoV, monocytes/macrophages and the dendritic cell network in mucosal tissues and highlights the fact that while these innate cells contribute to viral clearance, they probably also serve as shelters and vehicles to provide a mechanism for the virus to escape host mucosal innate immunity and disseminate systemically.",2016 Jul 9,"['Liu, Li', 'Wei, Qiang', 'Nishiura, Kenji', 'Peng, Jie', 'Wang, Haibo', 'Midkiff, Cecily', 'Alvarez, Xavier', 'Qin, Chuan', 'Lackner, Andrew', 'Chen, Zhiwei']",Mucosal Immunol,,,True
53273d3d1535bb285aea82a9cfe8244bb4729e41,PMC,Spatiotemporal Interplay of Severe Acute Respiratory Syndrome Coronavirus and Respiratory Mucosal Cells Drives Viral Dissemination in Rhesus Macaques,http://dx.doi.org/10.1038/mi.2015.127,PMC4900951,26647718,NO-CC CODE,"Innate immune responses play a critical role in the control of early virus replication and dissemination. It remains unknown, however, how SARS-CoV evades respiratory innate immunity to establish a systemic infection. Here, we show in Chinese macaques that SARS-CoV traversed the mucosa through the respiratory tract within 2 days, resulting in extensive mucosal infiltration by T cells, MAC387(+) and CD163(+) monocytes/macrophages followed by limited viral replication in the lung but persistent viral shedding into the upper airway. Mucosal monocytes/macrophages sequestered virions in intracellular vesicles together with infected Langerhans cells (LCs) and migrated into the tonsils and/or draining lymph nodes (LNs) within 2 days. In lymphoid tissues, viral RNA and proteins were detected in infected monocytes upon differentiation into dendritic cells (DCs) within 3 days. Systemic viral dissemination was observed within 7 days. This study provides a comprehensive overview of the spatiotemporal interactions of SARS-CoV, monocytes/macrophages and the dendritic cell network in mucosal tissues and highlights the fact that while these innate cells contribute to viral clearance, they probably also serve as shelters and vehicles to provide a mechanism for the virus to escape host mucosal innate immunity and disseminate systemically.",2016 Jul 9,"['Liu, Li', 'Wei, Qiang', 'Nishiura, Kenji', 'Peng, Jie', 'Wang, Haibo', 'Midkiff, Cecily', 'Alvarez, Xavier', 'Qin, Chuan', 'Lackner, Andrew', 'Chen, Zhiwei']",Mucosal Immunol,,,False
35280a72bb06b25d4a02e38efd412e97a40883c5,PMC,"Hepatitis E Virus Infection in Dromedaries, North and East Africa, United Arab Emirates, and Pakistan, 1983–2015",http://dx.doi.org/10.3201/eid2207.160168,PMC4918144,27315454,NO-CC CODE,"A new hepatitis E virus (HEV-7) was recently found in dromedaries and 1 human from the United Arab Emirates. We screened 2,438 dromedary samples from Pakistan, the United Arab Emirates, and 4 African countries. HEV-7 is long established, diversified and geographically widespread. Dromedaries may constitute a neglected source of zoonotic HEV infections.",2016 Jul,"['Rasche, Andrea', 'Saqib, Muhammad', 'Liljander, Anne M.', 'Bornstein, Set', 'Zohaib, Ali', 'Renneker, Stefanie', 'Steinhagen, Katja', 'Wernery, Renate', 'Younan, Mario', 'Gluecks, Ilona', 'Hilali, Mosaad', 'Musa, Bakri E.', 'Jores, Joerg', 'Wernery, Ulrich', 'Drexer, Jan Felix', 'Drosten, Christian', 'Corman, Victor Max']",Emerg Infect Dis,,,True
10f5615e0997e9d30c6a42a2d91e8cc9e896b8f4,PMC,"Hepatitis E Virus Infection in Dromedaries, North and East Africa, United Arab Emirates, and Pakistan, 1983–2015",http://dx.doi.org/10.3201/eid2207.160168,PMC4918144,27315454,NO-CC CODE,"A new hepatitis E virus (HEV-7) was recently found in dromedaries and 1 human from the United Arab Emirates. We screened 2,438 dromedary samples from Pakistan, the United Arab Emirates, and 4 African countries. HEV-7 is long established, diversified and geographically widespread. Dromedaries may constitute a neglected source of zoonotic HEV infections.",2016 Jul,"['Rasche, Andrea', 'Saqib, Muhammad', 'Liljander, Anne M.', 'Bornstein, Set', 'Zohaib, Ali', 'Renneker, Stefanie', 'Steinhagen, Katja', 'Wernery, Renate', 'Younan, Mario', 'Gluecks, Ilona', 'Hilali, Mosaad', 'Musa, Bakri E.', 'Jores, Joerg', 'Wernery, Ulrich', 'Drexer, Jan Felix', 'Drosten, Christian', 'Corman, Victor Max']",Emerg Infect Dis,,,False
a8fcb5f33a550dbbf4e54a3ce58f45e4a3e17567,PMC,"New Chimeric Porcine Coronavirus in Swine Feces, Germany, 2012",http://dx.doi.org/10.3201/eid2207.160179,PMC4918154,27070291,NO-CC CODE,,2016 Jul,"['Akimkin, Valerij', 'Beer, Martin', 'Blome, Sandra', 'Hanke, Dennis', 'Höper, Dirk', 'Jenckel, Maria', 'Pohlmann, Anne']",Emerg Infect Dis,,,True
897d4e1dcee3e63aadca1539aebef3d439bb11ab,PMC,"New Chimeric Porcine Coronavirus in Swine Feces, Germany, 2012",http://dx.doi.org/10.3201/eid2207.160179,PMC4918154,27070291,NO-CC CODE,,2016 Jul,"['Akimkin, Valerij', 'Beer, Martin', 'Blome, Sandra', 'Hanke, Dennis', 'Höper, Dirk', 'Jenckel, Maria', 'Pohlmann, Anne']",Emerg Infect Dis,,,False
7084dcfb81d40460f7ea05abe01a04285a45b095,PMC,"Response to Emergence of Middle East Respiratory Syndrome Coronavirus, Abu Dhabi, United Arab Emirates, 2013–2014",http://dx.doi.org/10.3201/eid2207.160040,PMC4918155,27314227,NO-CC CODE,"In January 2013, several months after Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia, Abu Dhabi, United Arab Emirates, began surveillance for MERS-CoV. We analyzed medical chart and laboratory data collected by the Health Authority–Abu Dhabi during January 2013–May 2014. Using real-time reverse transcription PCR, we tested respiratory tract samples for MERS-CoV and identified 65 case-patients. Of these patients, 23 (35%) were asymptomatic at the time of testing, and 4 (6%) showed positive test results for >3 weeks (1 had severe symptoms and 3 had mild symptoms). We also identified 6 clusters of MERS-CoV cases. This report highlights the potential for virus shedding by mildly ill and asymptomatic case-patients. These findings will be useful for MERS-CoV management and infection prevention strategies.",2016 Jul,"['Al Hosani, Farida Ismail', 'Pringle, Kimberly', 'Al Mulla, Mariam', 'Kim, Lindsay', 'Pham, Huong', 'Alami, Negar N.', 'Khudhair, Ahmed', 'Hall, Aron J.', 'Aden, Bashir', 'El Saleh, Feda', 'Al Dhaheri, Wafa', 'Al Bandar, Zyad', 'Bunga, Sudhir', 'Abou Elkheir, Kheir', 'Tao, Ying', 'Hunter, Jennifer C.', 'Nguyen, Duc', 'Turner, Andrew', 'Pradeep, Krishna', 'Sasse, Jurgen', 'Weber, Stefan', 'Tong, Suxiang', 'Whitaker, Brett L.', 'Haynes, Lia M.', 'Curns, Aaron', 'Gerber, Susan I.']",Emerg Infect Dis,,,True
6fc83e943aa7cc95190491c3c086c9edf16d4e6d,PMC,"Response to Emergence of Middle East Respiratory Syndrome Coronavirus, Abu Dhabi, United Arab Emirates, 2013–2014",http://dx.doi.org/10.3201/eid2207.160040,PMC4918155,27314227,NO-CC CODE,"In January 2013, several months after Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia, Abu Dhabi, United Arab Emirates, began surveillance for MERS-CoV. We analyzed medical chart and laboratory data collected by the Health Authority–Abu Dhabi during January 2013–May 2014. Using real-time reverse transcription PCR, we tested respiratory tract samples for MERS-CoV and identified 65 case-patients. Of these patients, 23 (35%) were asymptomatic at the time of testing, and 4 (6%) showed positive test results for >3 weeks (1 had severe symptoms and 3 had mild symptoms). We also identified 6 clusters of MERS-CoV cases. This report highlights the potential for virus shedding by mildly ill and asymptomatic case-patients. These findings will be useful for MERS-CoV management and infection prevention strategies.",2016 Jul,"['Al Hosani, Farida Ismail', 'Pringle, Kimberly', 'Al Mulla, Mariam', 'Kim, Lindsay', 'Pham, Huong', 'Alami, Negar N.', 'Khudhair, Ahmed', 'Hall, Aron J.', 'Aden, Bashir', 'El Saleh, Feda', 'Al Dhaheri, Wafa', 'Al Bandar, Zyad', 'Bunga, Sudhir', 'Abou Elkheir, Kheir', 'Tao, Ying', 'Hunter, Jennifer C.', 'Nguyen, Duc', 'Turner, Andrew', 'Pradeep, Krishna', 'Sasse, Jurgen', 'Weber, Stefan', 'Tong, Suxiang', 'Whitaker, Brett L.', 'Haynes, Lia M.', 'Curns, Aaron', 'Gerber, Susan I.']",Emerg Infect Dis,,,False
0f82974698355743046b60766dc767f02c357ad0,PMC,Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.3201/eid2207.160022,PMC4918159,27191188,NO-CC CODE,"Preclinical development of and research on potential Middle East respiratory syndrome coronavirus (MERS-CoV) medical countermeasures remain preliminary; advancements are needed before most countermeasures are ready to be tested in human clinical trials. Research priorities include standardization of animal models and virus stocks for studying disease pathogenesis and efficacy of medical countermeasures; development of MERS-CoV diagnostics; improved access to nonhuman primates to support preclinical research; studies to better understand and control MERS-CoV disease, including vaccination studies in camels; and development of a standardized clinical trial protocol. Partnering with clinical trial networks in affected countries to evaluate safety and efficacy of investigational therapeutics will strengthen efforts to identify successful medical countermeasures.",2016 Jul,"['Uyeki, Timothy M.', 'Erlandson, Karl J.', 'Korch, George', 'O’Hara, Michael', 'Wathen, Michael', 'Hu-Primmer, Jean', 'Hojvat, Sally', 'Stemmy, Erik J.', 'Donabedian, Armen']",Emerg Infect Dis,,,True
24da9eb1bf5b54581deda2e999cd5058674ceac4,PMC,"Tropheryma whipplei as a Cause of Epidemic Fever, Senegal, 2010–2012",http://dx.doi.org/10.3201/eid2207.150441,PMC4918168,27314980,NO-CC CODE,"The bacterium Tropheryma whipplei, which causes Whipple disease in humans, is commonly detected in the feces of persons in Africa. It is also associated with acute infections. We investigated the role of T. whipplei in febrile patients from 2 rural villages in Senegal. During June 2010–March 2012, we collected whole-blood finger-prick samples from 786 febrile and 385 healthy villagers. T. whipplei was detected in blood specimens from 36 (4.6%) of the 786 febrile patients and in 1 (0.25%) of the 385 apparently healthy persons. Of the 37 T. whipplei cases, 26 (70.2%) were detected in August 2010. Familial cases and a potential new genotype were observed. The patients’ symptoms were mainly headache (68.9%) and cough (36.1%). Our findings suggest that T. whipplei is a cause of epidemic fever in Senegal.",2016 Jul,"['Bassene, Hubert', 'Mediannikov, Oleg', 'Socolovschi, Cristina', 'Ratmanov, Pavel', 'Keita, Alpha K.', 'Sokhna, Cheikh', 'Raoult, Didier', 'Fenollar, Florence']",Emerg Infect Dis,,,True
3544f2f3beb5aec79815ae9ba463173cbe768172,PMC,Use of Plasma Therapy for Severe Fever with Thrombocytopenia Syndrome Encephalopathy,http://dx.doi.org/10.3201/eid2207.151791,PMC4918172,27315224,NO-CC CODE,,2016 Jul,"['Park, Se Yoon', 'Choi, WooYoung', 'Chong, Yong Pil', 'Park, Sun-Whan', 'Wang, Eun Byeol', 'Lee, Won-Ja', 'Jee, Youngmee', 'Kwon, Seog-Woon', 'Kim, Sung-Han']",Emerg Infect Dis,,,True
06eb8783f024a97d3bb159b01818ff6284123bb1,PMC,Use of Plasma Therapy for Severe Fever with Thrombocytopenia Syndrome Encephalopathy,http://dx.doi.org/10.3201/eid2207.151791,PMC4918172,27315224,NO-CC CODE,,2016 Jul,"['Park, Se Yoon', 'Choi, WooYoung', 'Chong, Yong Pil', 'Park, Sun-Whan', 'Wang, Eun Byeol', 'Lee, Won-Ja', 'Jee, Youngmee', 'Kwon, Seog-Woon', 'Kim, Sung-Han']",Emerg Infect Dis,,,False
2bf8ae683ef919a724c5623efda3a71110d57ddd,PMC,Structural basis for viral 5′-PPP-RNA recognition by human IFIT proteins,http://dx.doi.org/10.1038/nature11783,PMC4931921,23334420,NO-CC CODE,"IFIT proteins are interferon-inducible, innate immune effector molecules that are thought to confer antiviral defence through disruption of protein-protein interactions in the host translation initiation machinery. However, recently it was discovered that IFITs could directly recognize viral RNA bearing a 5′-triphosphate group (PPP-RNA), which is a molecular signature that distinguishes it from host RNA. Here, we report crystal structures of human IFIT5, its complex with PPP-RNAs, and an N-terminal fragment of IFIT1. The structures reveal a new helical domain that houses a positively charged cavity designed to specifically engage only single stranded PPP-RNA, thus distinguishing it from the canonical cytosolic sensor of double stranded viral PPP-RNA, RIG-I. Mutational analysis, proteolysis and gel-shift assays reveal that PPP-RNA is bound in a non-sequence specific manner and requires approximately a 3-nucleotide 5′-overhang. Abrogation of PPP-RNA binding in IFIT1 and IFIT5 were found to cause a defect in the anti-viral response by HEK cells. These results demonstrate the mechanism by which IFIT proteins selectively recognize viral RNA and lend insight into their downstream effector function.",2013 Feb 7,"['Abbas, Yazan M.', 'Pichlmair, Andreas', 'Górna, Maria W.', 'Superti-Furga, Giulio', 'Nagar, Bhushan']",Nature,,,True
24a4abb7e742c132b76b859fd53acfc1a126ba05,PMC,Structural basis for viral 5′-PPP-RNA recognition by human IFIT proteins,http://dx.doi.org/10.1038/nature11783,PMC4931921,23334420,NO-CC CODE,"IFIT proteins are interferon-inducible, innate immune effector molecules that are thought to confer antiviral defence through disruption of protein-protein interactions in the host translation initiation machinery. However, recently it was discovered that IFITs could directly recognize viral RNA bearing a 5′-triphosphate group (PPP-RNA), which is a molecular signature that distinguishes it from host RNA. Here, we report crystal structures of human IFIT5, its complex with PPP-RNAs, and an N-terminal fragment of IFIT1. The structures reveal a new helical domain that houses a positively charged cavity designed to specifically engage only single stranded PPP-RNA, thus distinguishing it from the canonical cytosolic sensor of double stranded viral PPP-RNA, RIG-I. Mutational analysis, proteolysis and gel-shift assays reveal that PPP-RNA is bound in a non-sequence specific manner and requires approximately a 3-nucleotide 5′-overhang. Abrogation of PPP-RNA binding in IFIT1 and IFIT5 were found to cause a defect in the anti-viral response by HEK cells. These results demonstrate the mechanism by which IFIT proteins selectively recognize viral RNA and lend insight into their downstream effector function.",2013 Feb 7,"['Abbas, Yazan M.', 'Pichlmair, Andreas', 'Górna, Maria W.', 'Superti-Furga, Giulio', 'Nagar, Bhushan']",Nature,,,True
77992c5e2e8442d8786bd1c80ec5b336680ed03b,PMC,Influenza virus assays based on virus‐inducible reporter cell lines,http://dx.doi.org/10.1111/j.1750-2659.2009.00095.x,PMC4940803,21462401,NO-CC CODE,"Background  Virus‐inducible reporter genes have been used as the basis of virus detection and quantitation assays for a number of viruses. A strategy for influenza A virus‐induction of a reporter gene was recently described. In this report, we describe the extension of this strategy to influenza B virus, the generation of stable cell lines with influenza A and B virus‐inducible reporter genes, and the use of these cells in various clinically relevant viral assays. Each of the cell lines described herein constitutively express an RNA transcript that contains a reporter gene coding region flanked by viral 5′‐ and 3′‐untranslated regions (UTR) and therefore mimics an influenza virus genomic segment. Upon infection of the cells with influenza virus the virus‐inducible reporter gene segment (VIRGS) is replicated and transcribed by the viral polymerase complex resulting in reporter gene expression. Findings  Reporter gene induction occurs after infection with a number of laboratory strains and clinical isolates of influenza virus including several H5N1 strains. The induction is dose‐dependent and highly specific for influenza A or influenza B viruses. Conclusions  These cell lines provide the basis of simple, rapid, and objective assays that involve virus quantitation such as determination of viral titer, assessment of antiviral susceptibility, and determination of antibody neutralization titer. These cell lines could be very useful for influenza virus researchers and vaccine manufacturers.",2009 Sep 13,"['Li, Yunsheng', 'Larrimer, Audrey', 'Curtiss, Teresa', 'Kim, Jaekyung', 'Jones, Abby', 'Baird‐Tomlinson, Heather', 'Pekosz, Andrew', 'Olivo, Paul D.']",Influenza Other Respir Viruses,,,True
0fe7366fd2acdb22f69d45c7373adf169a4636db,PMC,Respiratory viruses in children with cystic fibrosis: viral detection and clinical findings,http://dx.doi.org/10.1111/j.1750-2659.2011.00292.x,PMC4941093,21955319,NO-CC CODE,"Please cite this paper as: Burns et al. (2011) Respiratory viruses in children with cystic fibrosis: viral detection and clinical findings. Influenza and Other Respiratory Viruses 6(3), 218–223. Background  Viral detection from different respiratory sample types in children with cystic fibrosis (CF) is facilitated by available molecular methods, but optimum sampling strategies have not been identified. In addition, associations between viral detection and respiratory symptoms are not well described. Objectives  Study goals were to compare molecular detection of viruses from concurrent upper airway and sputum samples in children with CF and to describe relative frequency of respiratory viral infections and identify potential clinical associations. Methods  We conducted a 2‐year prospective surveillance study in 44 children with CF aged 6–18 years. Upper airway and sputum samples were collected quarterly and during pulmonary exacerbations and tested for respiratory syncytial virus (RSV), influenza viruses, parainfluenza viruses types 1–4, human metapneumovirus, coronaviruses, rhinoviruses, and adenoviruses. Physical exams and symptom surveys were used to identify respiratory signs and symptoms. Results  Upper airway samples were collected at 359 visits; concordance of PCR‐based viral detection was examined in a subset of paired upper airway and sputum samples from 21 participants at 92 visits. Rhinovirus was the most commonly detected virus (23·1% overall), and rhinovirus detection was the same for both sample types (21·7% each). Sensitivity and specificity for the detection of rhinovirus in sputum relative to upper airway sampling were 70% and 91·7%, respectively. Respiratory symptoms associated with rhinovirus detection included increased cough, increased nasal congestion, increased sputum production, and wheezing. Conclusions  A relatively high frequency of rhinovirus detection was observed by either upper airway or sputum samples, and clinical findings suggest a significant‐associated symptom burden.",2012 May 29,"['Burns, Jane L.', 'Emerson, Julia', 'Kuypers, Jane', 'Campbell, Angela P.', 'Gibson, Ronald L.', 'McNamara, Sharon', 'Worrell, Kelly', 'Englund, Janet A.']",Influenza Other Respir Viruses,,,True
a4b7fac91178fae8acd884c584fbbb525b883c65,PMC,A review of medical masks and respirators for use during an influenza pandemic,http://dx.doi.org/10.1111/j.1750-2659.2009.00101.x,PMC4941551,19702582,NO-CC CODE,,2009 Sep 18,"['Seale, Holly', 'Dwyer, Dominic E.', 'Cowling, Benjamin J.', 'Wang, Quanyi', 'Yang, Peng', 'MacIntyre, C. Raina']",Influenza Other Respir Viruses,,,True
c657dee5652708f18918e1c24b24d2f98cc1c4af,PMC,A cluster randomized clinical trial comparing fit‐tested and non‐fit‐tested N95 respirators to medical masks to prevent respiratory virus infection in health care workers,http://dx.doi.org/10.1111/j.1750-2659.2011.00198.x,PMC4941587,21477136,NO-CC CODE,"Please cite this paper as: MacIntyre et al. (2011) A cluster randomized clinical trial comparing fit‐tested and non‐fit‐tested N95 respirators to medical masks to prevent respiratory virus infection in health care workers. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2010.00198.x. Background  We compared the efficacy of medical masks, N95 respirators (fit tested and non fit tested), in health care workers (HCWs). Methods  A cluster randomized clinical trial (RCT) of 1441 HCWs in 15 Beijing hospitals was performed during the 2008/2009 winter. Participants wore masks or respirators during the entire work shift for 4 weeks. Outcomes included clinical respiratory illness (CRI), influenza‐like illness (ILI), laboratory‐confirmed respiratory virus infection and influenza. A convenience no‐mask/respirator group of 481 health workers from nine hospitals was compared. Findings  The rates of CRI (3·9% versus 6·7%), ILI (0·3% versus 0·6%), laboratory‐confirmed respiratory virus (1·4% versus 2·6%) and influenza (0·3% versus 1%) infection were consistently lower for the N95 group compared to medical masks. By intention‐to‐treat analysis, when P values were adjusted for clustering, non‐fit‐tested N95 respirators were significantly more protective than medical masks against CRI, but no other outcomes were significant. The rates of all outcomes were higher in the convenience no‐mask group compared to the intervention arms. There was no significant difference in outcomes between the N95 arms with and without fit testing. Rates of fit test failure were low. In a post hoc analysis adjusted for potential confounders, N95 masks and hospital level were significant, but medical masks, vaccination, handwashing and high‐risk procedures were not. Interpretation  Rates of infection in the medical mask group were double that in the N95 group. A benefit of respirators is suggested but would need to be confirmed by a larger trial, as this study may have been underpowered. The finding on fit testing is specific to the type of respirator used in the study and cannot be generalized to other respirators. Trial registration  Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN: ACTRN12609000257268 (http://www.anzctr.org.au).",2011 May 27,"['MacIntyre, Chandini Raina', 'Wang, Quanyi', 'Cauchemez, Simon', 'Seale, Holly', 'Dwyer, Dominic E.', 'Yang, Peng', 'Shi, Weixian', 'Gao, Zhanhai', 'Pang, Xinghuo', 'Zhang, Yi', 'Wang, Xiaoli', 'Duan, Wei', 'Rahman, Bayzidur', 'Ferguson, Neil']",Influenza Other Respir Viruses,,,True
e5869f8b8ecda2894a0ac35dc2f50bf56f24e72f,PMC,Journalists’ views about reporting avian influenza and a potential pandemic: a qualitative study,http://dx.doi.org/10.1111/j.1750-2659.2011.00319.x,PMC4941671,22176678,NO-CC CODE,"Please cite this paper as: Hooker et al. (20XX) Journalists’ views about reporting avian influenza and a potential pandemic: a qualitative study. Influenza and Other Respiratory Viruses 6(3), 224–229. Background  The mass media is a key component of any public communication strategy for influenza or other respiratory illnesses, but coverage can be variable. In this study, we explored the factors that influenced journalists’ coverage of avian influenza as a model for coverage of a potential influenza pandemic. Methods  This study involved semi‐structured interviews with 16 journalists from major Australian print, radio and television media organisations reporting on avian influenza and pandemic planning. Journalists, including reporters, editors and producers, were interviewed between October 2006 and August 2007. Thematic analysis was used to draw out major lessons for health communicators. Results  Coverage of avian influenza was influenced by a small set of news values: catastrophic potential, cultural and geographical proximity, unfamiliarity and uncertainty. Lack of novelty and the absence of compelling images led to a decline in coverage. Journalists expressed concerns about the accuracy and impacts of reporting, but saw as critically important, their primary role as informants. They hence emphasised the importance of journalistic independence. Journalists all intended to continue working in a pandemic. Conclusions  Health experts need to adapt their timetables and resources to journalists’ needs to improve their mutual communication. In crisis situations, journalists communicate with the public efficiently and effectively, but expert and journalistic views on the role and content of coverage may diverge in the post‐acute, reflective phase of a crisis.",2012 May 17,"['Hooker, Claire', 'King, Catherine', 'Leask, Julie']",Influenza Other Respir Viruses,,,True
21b6c038511e8897875bae8dad4ee6f574bad5d2,PMC,"Respiratory viral infections in institutions from late stage of the first and second waves of pandemic influenza A (H1N1) 2009, Ontario, Canada",http://dx.doi.org/10.1111/j.1750-2659.2012.00336.x,PMC4941672,22353417,NO-CC CODE,"Please cite this paper as: Asner et al. (2012) Respiratory viral infections in institutions from late stage of the first and second waves of pandemic A (H1N1) 2009, Ontario, Canada. Influenza and Other Respiratory Viruses 6(3), e11–e15. We report the impact of respiratory viruses on various outbreak settings by using surveillance data from the late first and second wave periods of the 2009 pandemic. A total of 278/345(78·5%) outbreaks tested positive for at least one respiratory virus by multiplex PCR. We detected A(H1N1)pdm09 in 20·6% of all reported outbreaks of which 54·9% were reported by camps, schools, and day cares (CSDs) and 29·6% by long‐term care facilities (LCFTs), whereas enterovirus/human rhinovirus (ENT/HRV) accounted for 62% outbreaks of which 83·7% were reported by long‐term care facilities (LCTFs). ENT/HRV was frequently identified in LTCF outbreaks involving elderly residents, whereas in CSDs, A(H1N1)pdm09 was primarily detected.",2012 May 21,"['Asner, Sandra', 'Peci, Adriana', 'Marchand‐Austin, Alex', 'Winter, Anne‐Luise', 'Olsha, Romy', 'Kristjanson, Erik', 'Low, Donald E.', 'Gubbay, Jonathan B.']",Influenza Other Respir Viruses,,,True
ac45f663ed3b7143b944a5385b5d82754087a6af,PMC,Molecular and phylogenetic analysis of matrix gene of avian influenza viruses isolated from wild birds and live bird markets in the USA,http://dx.doi.org/10.1111/irv.12003,PMC4941746,22958470,NO-CC CODE,"Please cite this paper as: Chander et al. (2012) Molecular and phylogenetic analysis of matrix gene of avian influenza viruses isolated from wild birds and live bird markets in the USA. Influenza and Other Respiratory Viruses 7(4), 513–520. Background  Wild birds are the natural hosts for influenza A viruses (IAVs) and provide a niche for the maintenance of this virus. Objectives  This study was undertaken to analyze nucleotide sequences of the matrix (M) gene of AIVs isolated from wild birds and live bird markets (LBMs) to index the changes occurring in this gene. Methods  M‐gene of 229 avian influenza virus (AIV) isolates obtained from wild birds and LBMs was amplified and sequenced. Full‐length sequences (∼900 nt.) thus obtained were analyzed to identify changes that may be associated with resistance to adamantanes. Phylogenetic analysis of all sequences was performed using clustalw, and evolutionary distances were calculated by maximum composite likelihood method using mega (ver. 5.0) software. Results  Twenty‐seven different viral subtypes were represented with H3N8 being the most dominant subtype in wild birds and H7N2 being the predominant subtype among isolates from LBMs. Phylogenetic analysis of the M‐gene showed a high degree of nucleotide sequence identity with US isolates of AIVs but not with those of Asian or European lineages. While none of the isolates from wild birds had any antiviral resistance–associated mutations, 17 LBM isolates carried polymorphisms known to cause reduced susceptibility to antiviral drugs (adamantanes). Of these 17 isolates, 16 had S31N change and one isolate had V27A mutation. Conclusions  These results indicate independent evolution of M‐gene in the absence of any antiviral drugs leading to mutations causing resistance indicating the need for continued active surveillance of AIVs.",2013 Jul 8,"['Chander, Yogesh', 'Jindal, Naresh', 'Sreevatsan, Srinand', 'Stallknecht, David E.', 'Goyal, Sagar M.']",Influenza Other Respir Viruses,,,True
f0f56c1e82c717ced3a4f2ca872dd303581ea750,PMC,"Inter‐ and intraspecies transmission of canine influenza virus (H3N2) in dogs, cats, and ferrets",http://dx.doi.org/10.1111/j.1750-2659.2012.00379.x,PMC4941754,22616918,NO-CC CODE,"Background  The emergence of zoonotic viruses in domestic animals is a significant public health concern. Canine influenza virus (CIV) H3N2 is a virus that can infect companion animals and is, therefore, a potential public health concern. Objective  This study investigated the inter‐ and intraspecies transmission of CIV among dogs, cats, and ferrets, under laboratory conditions, to determine whether transmission of the virus was possible between as well as within these domestic animal species. Method  The transmission routes for inter‐ and intraspecies transmission were airborne and direct contact, respectively. Transmission was conducted through intranasal infection of dogs followed by exposure to either cats or ferrets and by comingling infected and naïve animals of the same species. Results  The interspecies transmission of CIV H3N2 via airborne was only observed from dogs to cats and not from dogs to ferrets. However, direct intranasal infection of either cats or ferrets with CIV could induce influenza‐like clinical signs, viral shedding, and serological responses. Additionally, naïve cats and ferrets could be infected by CIV via direct contact with infected animals of the same species. Conclusion  Cats appear to be another susceptible host of CIV H3N2, whereas ferrets are not likely natural hosts. The molecular‐based mechanism of interspecies and intraspecies transmission of CIV H3N2 should be further studied.",2013 May 23,"['Kim, Hyekwon', 'Song, Daesub', 'Moon, Hyoungjoon', 'Yeom, Minjoo', 'Park, Seongjun', 'Hong, Minki', 'Na, Woonseong', 'Webby, Richard J.', 'Webster, Robert G.', 'Park, Bongkyun', 'Kim, Jeong‐Ki', 'Kang, Bokyu']",Influenza Other Respir Viruses,,,True
4f1b29ad62f545bbbce05dcdf1d7a2ce0b72e1d4,PMC,A sensitive retroviral pseudotype assay for influenza H5N1‐neutralizing antibodies,http://dx.doi.org/10.1111/j.1750-2659.2007.00016.x,PMC4941878,19453415,NO-CC CODE,"Background  The World Health Organisation (WHO) recommended the development of simple, safe, sensitive and specific neutralization assays for avian influenza antibodies. We have used retroviral pseudotypes bearing influenza H5 hemagglutinin (HA) as safe, surrogate viruses for influenza neutralization assays which can be carried out at Biosafety Level 2. Results  Using our assay, sera from patients who had recovered from infection with influenza H5N1, and sera from animals experimentally immunized or infected with H5 tested positive for the presence of neutralizing antibodies to H5N1. Pseudotype neutralizing antibody titers were compared with titers obtained by hemagglutinin inhibition (HI) assays and microneutralization (MN) assays using live virus, and showed a high degree of correlation, sensitivity and specificity. Conclusions  The pseudotype neutralization assay is as sensitive as horse erythrocyte HI and MN for the detection of antibodies to H5N1. It is safer, and can be applied in a high‐throughput format for human and animal surveillance and for the evaluation of vaccines.",2007 May 26,"['Temperton, Nigel J.', 'Hoschler, Katja', 'Major, Diane', 'Nicolson, Carolyn', 'Manvell, Ruth', 'Hien, Vo Minh', 'Ha, Do Quang', 'De Jong, Menno', 'Zambon, Maria', 'Takeuchi, Yasuhiro', 'Weiss, Robin A.']",Influenza Other Respir Viruses,,,True
8ee9f67cb46223274974fce223eb6c5d4834d809,PMC,Bioaerosol sampling for the detection of aerosolized influenza virus,http://dx.doi.org/10.1111/j.1750-2659.2007.00020.x,PMC4941879,19453416,NO-CC CODE,"Background Influenza virus was used to characterize the efficacy of a cyclone‐based, two‐stage personal bioaerosol sampler for the collection and size fractionation of aerosolized viral particles. Methods A Collison single‐jet nebulizer was used to aerosolize the attenuated FluMist® vaccine into a calm‐air settling chamber. Viral particles were captured with bioaerosol samplers that utilize 2 microcentrifuge tubes to collect airborne particulates. The first tube (T1) collects particles greater than 1.8 μm in diameter, while the second tube (T2) collects particles between 1.0 and 1.8 μm, and the back‐up filter (F) collects submicron particles. Following aerosolization, quantitative PCR was used to detect and quantify H1N1 and H3N2 influenza strains. Results Based on qPCR results, we demonstrate that aerosolized viral particles were efficiently collected and separated according to aerodynamic size using the two‐stage bioaerosol sampler. Most viral particles were collected in T2 (1‐1.8 μm) and on the back‐up filter (< 1 μm) of the bioaerosol sampler. Furthermore, we found that the detection of viral particles with the two‐stage sampler was directly proportional to the collection time. Consequently, viral particle counts were significantly greater at 40 minutes in comparison to 5, 10 and 20 minute aerosol collection points. Conclusions Due to a lack of empirical data, aerosol transmission of influenza is often questioned. Using FluMist®, we demonstrated that a newly developed bioaerosol sampler is able to recover and size fractionate aerosolized viral particles. This sampler should be an important tool for studying viral transmission in clinical settings and may significantly contribute towards understanding the modes of influenza virus transmission.",2007 May 22,"['Blachere, Francoise M.', 'Lindsley, William G.', 'Slaven, James E.', 'Green, Brett J.', 'Anderson, Stacey E.', 'Chen, Bean T.', 'Beezhold, Don H.']",Influenza Other Respir Viruses,,,True
a618a87ac05377d6f665251c756bc2e8f77d34e6,PMC,Influenza vaccination coverage rates in Europe – covering five consecutive seasons (2001–2006) in five countries,http://dx.doi.org/10.1111/j.1750-2659.2008.00036.x,PMC4941886,19453429,NO-CC CODE,"Objective  To understand potential drivers and barriers to influenza vaccination in the general population. Methods  47 982 household surveys were conducted in five European countries between 2001 and 2006. Results  Overall influenza vaccination coverage increased over the years and reached 26·2% in 2005/06. Among the elderly ≥65 years, the rate increased significantly to 67·8% (2005/06). The most common reason for being vaccinated over the 5 years was the perception of influenza as a serious illness, which people want to avoid. The main reason for not getting vaccinated among those never previously vaccinated was feeling that they were unlikely to catch influenza. A recommendation by the family physician was the most encouraging factor for vaccination.",2007 Sep 28,"['Holm, Majbrit V.', 'Blank, Patricia R.', 'Szucs, Thomas D.']",Influenza Other Respir Viruses,,,True
8695a2f335ffb2ccdaa84863bf31002555d0828f,PMC,Chloroquine is effective against influenza A virus in vitro but not in vivo,http://dx.doi.org/10.1111/j.1750-2659.2007.00027.x,PMC4941887,19453426,NO-CC CODE,"Background  Chloroquine is an inexpensive and widely available 9‐aminoquinolone used in the management of malaria. Recently, in vitro assays suggest that chloroquine may have utility in the treatment of several viral infections including influenza. Objectives  We sought to test whether chloroquine is effective against influenza in vivo in relevant animal models. Methods  The effectiveness of chloroquine at preventing or ameliorating influenza following viral challenge was assessed in established mouse and ferret disease models. Results  Although active against influenza viruses in vitro, chloroquine did not prevent the weight loss associated with influenza virus infection in mice after challenge with viruses expressing an H1 or H3 hemagglutinin protein. Similarly, clinical signs and viral replication in the nose of ferrets were not altered by treatment. Conclusions  Although in vitro results were promising, chloroquine was not effective as preventive therapy in vivo in standard mouse and ferret models of influenza virus infection. This dampens enthusiasm for the potential utility of the drug for humans with influenza.",2007 Sep 21,"['Vigerust, David J.', 'McCullers, Jonathan A.']",Influenza Other Respir Viruses,,,True
13b2340ab0e81bc4d29b8c0fb0a6894490c003b1,PMC,Sialic acid tissue distribution and influenza virus tropism,http://dx.doi.org/10.1111/j.1750-2659.2008.00051.x,PMC4941897,19453419,NO-CC CODE,"Abstract  Avian influenza A viruses exhibit a strong preference for using α2,3‐linked sialic acid as a receptor. Until recently, the presumed lack of this receptor in human airways was believed to constitute an efficient barrier to avian influenza A virus infection of humans. Recent zoonotic outbreaks of avian influenza A virus have triggered researchers to analyse tissue distribution of sialic acid in further detail. Here, we review and extend the current knowledge about sialic acid distribution in human tissues, and discuss viruses with ocular tropism and their preference for α2,3‐linked sialic acid.",2008 Sep 8,"['Kumlin, Urban', 'Olofsson, Sigvard', 'Dimock, Ken', 'Arnberg, Niklas']",Influenza Other Respir Viruses,,,True
e59218b42f783a547778cbf247cce2552f9a163a,PMC,Genetic diversity of swine influenza viruses isolated from pigs during 2000 to 2005 in Thailand,http://dx.doi.org/10.1111/j.1750-2659.2008.00062.x,PMC4941901,19453423,NO-CC CODE,"Background  Recent studies have revealed the existence of genetic diversity in swine influenza viruses (SIVs) in the world. In Thailand, there has been a little information on the molecular characteristics of the SIVs since the first isolation of viruses of H1N1 and H3N2 subtypes in the late 1970s. Our previous study demonstrated that Thai H1N1 SIVs possessed the classical swine H1 and avian‐like swine N1 genes (Takemae et al., Proceedings of the Options for the Control of Influenza VI.2007;350–353). Objectives  In the present study, we genetically characterized 12 SIVs including those of H1N1, H1N2 and H3N2 subtypes isolated between 2000 and 2005. Methods  We determined the entire nucleotide sequences of the eight gene segments of those isolates. Results  Phylogenetic analysis revealed the existence of nine distinct genotypes amongst the Thai SIVs. These genotypes arose from multiple introductions of classical swine, avian‐like swine and human viruses. The existence of two distinct sublineages within classical swine H1 and NS, avian‐like swine PA and M and human H3 and N2 genes of the Thai SIVs suggested that introduction of viruses of classical swine, avian‐like swine and human origins occurred twice respectively into the Thai pig population. The predominance of avian‐like swine genes amongst the Thai SIVs was evident. In particular, three polymerase (PB1, PB2 and PA) and matrix genes of avian‐like swine origin were retained in all the Thai SIVs examined. Conclusions  These observations may suggest that genes of avian‐like swine lineages have some advantages to be maintained in pigs as seen in the SIVs established through multiple introductions in other regions.",2008 Sep 24,"['Takemae, Nobuhiro', 'Parchariyanon, Sujira', 'Damrongwatanapokin, Sudarat', 'Uchida, Yuko', 'Ruttanapumma, Ruttapong', 'Watanabe, Chiaki', 'Yamaguchi, Shigeo', 'Saito, Takehiko']",Influenza Other Respir Viruses,,,True
c43a5466719bd6f3d36d415fdceb244e53d811a0,PMC,An ex vivo swine tracheal organ culture for the study of influenza infection,http://dx.doi.org/10.1111/j.1750-2659.2009.00119.x,PMC4941949,20021502,NO-CC CODE,"Background  The threat posed by swine influenza viruses with potential to transmit from pig populations to other hosts, including humans, requires the development of new experimental systems to study different aspects of influenza infection. Ex vivo organ culture (EVOC) systems have been successfully used in the study of both human and animal respiratory pathogens. Objectives  We aimed to develop an air interface EVOC using pig tracheas in the study of influenza infection demonstrating that tracheal explants can be effectively maintained in organ culture and support productive influenza infection. Methods  Tracheal explants were maintained in the air interface EVOC system for 7 days. Histological characteristics were analysed with different staining protocols and co‐ordinated ciliary movement on the epithelial surface was evaluated through a bead clearance assay. Explants were infected with a swine H1N1 influenza virus. Influenza infection of epithelial cells was confirmed by immunohistochemistry and viral replication was quantified by plaque assays and real‐time RT‐PCR. Results  Histological analysis and bead clearance assay showed that the tissue architecture of the explants was maintained for up to 7 days, while ciliary movement exhibited a gradual decrease after 4 days. Challenge with swine H1N1 influenza virus showed that the EVOC tracheal system shows histological changes consistent with in vivo influenza infection and supported productive viral replication over multiple cycles of infection. Conclusion  The air interface EVOC system using pig trachea described here constitutes a useful biological tool with a wide range of applications in the study of influenza infection.",2010 Jan 9,"['Nunes, Sandro F.', 'Murcia, Pablo R.', 'Tiley, Laurence S.', 'Brown, Ian H.', 'Tucker, Alexander W.', 'Maskell, Duncan J.', 'Wood, James Lionel N.']",Influenza Other Respir Viruses,,,True
5dc2b500e260938d6db9120669c23b90942bb07c,PMC,Annual influenza vaccination: coverage and attitudes of primary care staff in Australia,http://dx.doi.org/10.1111/j.1750-2659.2010.00158.x,PMC4942009,21306577,NO-CC CODE,"Please cite this paper as: Ward et al. (2011) Annual influenza vaccination: coverage and attitudes of primary care staff in Australia. Influenza and Other Respiratory Viruses 5(2), 135–141. Background  Annual influenza vaccination is recommended for all Australian health care workers (HCWs) including those working in primary health care. There is limited published data on coverage, workplace provision, attitudes and personal barriers to influenza vaccination amongst primary health care staff. The aim of this study was to contribute to the limited literature base in this important area by investigating these issues in the primary health care setting in New South Wales (NSW), Australia. Methods  A postal survey was sent to general practitioners (GPs) and practice nurses (PNs) from inner city, semi‐urban and rural areas of NSW, Australia. There were 139 responses in total (response rate 36%) from 79 GPs (response rate 30%) and 60 PNs (response rate 46%). Results  Reported influenza vaccination coverage in both 2007 and 2008 was greater than 70%, with GPs reporting higher coverage than PNs in both years. The main barriers identified were lack of awareness of vaccination recommendations for general practice staff and concern about adverse effects from the vaccine. Conclusions  Rates of influenza vaccination coverage reported in this study were higher than in previous studies of hospital and institutional HCWs, though it is possible that the study design may have contributed to these higher results. Nevertheless, these findings highlight that more needs to be done to understand barriers to vaccination in this group, to inform the development of appropriate strategies to increase vaccination coverage in primary health care staff, with a special focus on PNs.",2011 Mar 12,"['Ward, Kirsten', 'Seale, Holly', 'Zwar, Nicholas', 'Leask, Julie', 'MacIntyre, C. Raina']",Influenza Other Respir Viruses,,,True
afcc1a28b96721fb9f9544943254ab73d656b635,PMC,Transmission parameters of the A/H1N1 (2009) influenza virus pandemic: a review,http://dx.doi.org/10.1111/j.1750-2659.2011.00234.x,PMC4942041,21668690,NO-CC CODE,"Please cite this paper as: Boëlle P‐Y et al. (2011) Transmission parameters of the A/H1N1 (2009) influenza virus pandemic: a review. Influenza and Other Respiratory Viruses 5(5), 306–316. Background  The new influenza virus A/H1N1 (2009), identified in mid‐2009, rapidly spread over the world. Estimating the transmissibility of this new virus was a public health priority. Methods  We reviewed all studies presenting estimates of the serial interval or generation time and the reproduction number of the A/H1N1 (2009) virus infection. Results  Thirteen studies documented the serial interval from household or close‐contact studies, with overall mean 3 days (95% CI: 2·4, 3·6); taking into account tertiary transmission reduced this estimate to 2·6 days. Model‐based estimates were more variable, from 1·9 to 6 days. Twenty‐four studies reported reproduction numbers for community‐based epidemics at the town or country level. The range was 1·2–3·1, with larger estimates reported at the beginning of the pandemic. Accounting for under‐reporting in the early period of the pandemic and limiting variation because of the choice of the generation time interval, the reproduction number was between 1·2 and 2·3 with median 1·5. Discussion  The serial interval of A/H1N1 (2009) flu was typically short, with mean value similar to the seasonal flu. The estimates of the reproduction number were more variable. Compared with past influenza pandemics, the median reproduction number was similar (1968) or slightly smaller (1889, 1918, 1957).",2011 Sep 31,"['Boëlle, Pierre‐Yves', 'Ansart, Séverine', 'Cori, Anne', 'Valleron, Alain‐Jacques']",Influenza Other Respir Viruses,,,True
590e55ca7451d6a3aad7b2d84a04b39bc864dbe7,PMC,"Health promotion practices as perceived by primary healthcare professionals at the Ministry of National Guard Health Affairs, Saudi Arabia",http://dx.doi.org/10.5339/qmj.2016.4,PMC4951748,27482512,NO-CC CODE,"Introduction: In recent years, several research studies have investigated health promotion practices in Saudi healthcare organizations, yet no published literature exists on health promotion practices of primary healthcare professionals working for the Ministry of National Guard Health Affairs (MNG-HA). Methods: A cross-sectional study was conducted in a convenience sample of 206 primary healthcare professionals at the MNG-HA. A self-reporting questionnaire was used to investigate the attitudes, awareness, satisfaction, and methods regarding health promotion practices of primary healthcare professionals. Results: Of the 206 primary healthcare professionals surveyed, 58.1% reported awareness of health promotion programs conducted in the hospitals and 64.6% reported that the health promotion system in the hospitals needs to be improved. Language barriers and cultural beliefs were viewed as obstacles to carrying out effective health promotion by 65% and 64.6% of primary healthcare professionals, respectively. The majority (79.9%) of the primary healthcare professionals perceived themselves as having the necessary skills to promote health and 80.6% believed that printed educational materials are the most prevalent method of health promotion/education, whereas 55.8% reported that counseling was the most preferred method of health promotion. Conclusion: The awareness level of health promotion policies, strategies, and programs conducted in the hospitals was not found to be satisfactory. Therefore, widespread training programs are recommended to improve the health promotion system in the hospitals. These programs include facilitating behavioral change, introducing health promotion policies and strategies in hospitals, mandatory workshops, and systematic reminders.",2016 Jun 15,"['Altamimi, Samar', 'Alshoshan, Feda', 'Al Shaman, Ghada', 'Tawfeeq, Nasser', 'Alasmary, May', 'Ahmed, Anwar E.']",Qatar Med J,,,True
149fee3f610ddebf8ad1045779c8af5fb1f40940,PMC,"Improving influenza vaccine virus selectionReport of a WHO informal consultation held at WHO headquarters, Geneva, Switzerland, 14–16 June 2010",http://dx.doi.org/10.1111/j.1750-2659.2011.00277.x,PMC4954460,21819547,NO-CC CODE,"•  For almost 60 years, the WHO Global Influenza Surveillance and Response System (GISRS) has been the key player in monitoring the evolution and spread of influenza viruses and recommending the strains to be used in human influenza vaccines. The GISRS has also worked to continually monitor and assess the risk posed by potential pandemic viruses and to guide appropriate public health responses. •  The expanded and enhanced role of the GISRS following the adoption of the International Health Regulations (2005), recognition of the continuing threat posed by avian H5N1 and the aftermath of the 2009 H1N1 pandemic provide an opportune time to critically review the process by which influenza vaccine viruses are selected. In addition to identifying potential areas for improvement, such a review will also help to promote greater appreciation by the wider influenza and policy‐making community of the complexity of influenza vaccine virus selection. •  The selection process is highly coordinated and involves continual year‐round integration of virological data and epidemiological information by National Influenza Centres (NICs), thorough antigenic and genetic characterization of viruses by WHO Collaborating Centres (WHOCCs) as part of selecting suitable candidate vaccine viruses, and the preparation of suitable reassortants and corresponding reagents for vaccine standardization by WHO Essential Regulatory Laboratories (ERLs). •  Ensuring the optimal effectiveness of vaccines has been assisted in recent years by advances in molecular diagnosis and the availability of more extensive genetic sequence data. However, there remain a number of challenging constraints including variations in the assays used, the possibility of complications resulting from non‐antigenic changes, the limited availability of suitable vaccine viruses and the requirement for recommendations to be made up to a year in advance of the peak of influenza season because of production constraints. •  Effective collaboration and coordination between human and animal influenza networks is increasingly recognized as an essential requirement for the improved integration of data on animal and human viruses, the identification of unusual influenza A viruses infecting human, the evaluation of pandemic risk and the selection of candidate viruses for pandemic vaccines. •  Training workshops, assessments and donations have led to significant increases in trained laboratory personnel and equipment with resulting expansion in both geographical surveillance coverage and in the capacities of NICs and other laboratories. This has resulted in a significant increase in the volume of information reported to WHO on the spread, intensity and impact of influenza. In addition, initiatives such as the WHO Shipment Fund Project have facilitated the timely sharing of clinical specimens and virus isolates and contributed to a more comprehensive understanding of the global distribution and temporal circulation of different viruses. It will be important to sustain and build upon the gains made in these and other areas. •  Although the haemagglutination inhibition (HAI) assay is likely to remain the assay of choice for the antigenic characterization of viruses in the foreseeable future, alternative assays – for example based upon advanced recombinant DNA and protein technologies – may be more adaptable to automation. Other technologies such as microtitre neuraminidase inhibition assays may also have significant implications for both vaccine virus selection and vaccine development. •  Microneutralization assays provide an important adjunct to the HAI assay in virus antigenic characterization. Improvements in the use and potential automation of such assays should facilitate large‐scale serological studies, while other advanced techniques such as epitope mapping should allow for a more accurate assessment of the quality of a protective immune response and aid the development of additional criteria for measuring immunity. •  Standardized seroepidemiological surveys to assess the impact of influenza in a population could help to establish well‐characterized banks of age‐stratified representative sera as a national, regional and global resource, while providing direct evidence of the specific benefits of vaccination. •  Advances in high‐throughput genetic sequencing coupled with advanced bioinformatics tools, together with more X‐ray crystallographic data, should accelerate understanding of the genetic and phenotypic changes that underlie virus evolution and more specifically help to predict the influence of amino acid changes on virus antigenicity. •  Complex mathematical modelling techniques are increasingly being used to gain insights into the evolution and epidemiology of influenza viruses. However, their value in predicting the timing and nature of future antigenic and genetic changes is likely to be limited at present. The application of simpler non‐mechanistic statistical algorithms, such as those already used as the basis of antigenic cartography, and phylogenetic modelling are more likely to be useful in facilitating vaccine virus selection and in aiding assessment of the pandemic potential of avian and other animal influenza viruses. •  The adoption of alternative vaccine technologies – such as live‐attenuated, quadrivalent or non‐HA‐based vaccines – has significant implications for vaccine virus selection, as well as for vaccine regulatory and manufacturing processes. Recent collaboration between the GISRS and vaccine manufacturers has resulted in the increased availability of egg isolates and high‐growth reassortants for vaccine production, the development of qualified cell cultures and the investigation of alternative methods of vaccine potency testing. WHO will continue to support these and other efforts to increase the reliability and timeliness of the global influenza vaccine supply. •  The WHO GISRS and its partners are continually working to identify improvements, harness new technologies and strengthen and sustain collaboration. WHO will continue in its central role of coordinating worldwide expertise to meet the increasing public health need for influenza vaccines and will support efforts to improve the vaccine virus selection process, including through the convening of periodic international consultations.",2012 Mar 8,"[None, 'Ampofo, William K.', 'Baylor, Norman', 'Cobey, Sarah', 'Cox, Nancy J.', 'Daves, Sharon', 'Edwards, Steven', 'Ferguson, Neil', 'Grohmann, Gary', 'Hay, Alan', 'Katz, Jacqueline', 'Kullabutr, Kornnika', 'Lambert, Linda', 'Levandowski, Roland', 'Mishra, A. C.', 'Monto, Arnold', 'Siqueira, Marilda', 'Tashiro, Masato', 'Waddell, Anthony L.', 'Wairagkar, Niteen', 'Wood, John', 'Zambon, Maria', 'Zhang, Wenqing']",Influenza Other Respir Viruses,,,True
ec9040732c2587bf4776b0953905e8a87828e8cf,PMC,A systematic review of community-based interventions for emerging zoonotic infectious diseases in Southeast Asia,http://dx.doi.org/10.11124/jbisrir-2013-801,PMC4962925,,NO-CC CODE,"BACKGROUND: Southeast Asia has been at the epicentre of recent epidemics of emerging and re-emerging zoonotic diseases. Community-based surveillance and control interventions have been heavily promoted but the most effective interventions have not been identified. OBJECTIVES: This review evaluated evidence for the effectiveness of community-based surveillance interventions at monitoring and identifying emerging infectious disease; the effectiveness of community-based control interventions at reducing rates of emerging infectious disease; and contextual factors that influence intervention effectiveness. INCLUSION CRITERIA: Participants Communities in Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, the Philippines, Singapore, Thailand and Viet Nam. Types of intervention(s) Non-pharmaceutical, non-vaccine, and community-based surveillance or prevention and control interventions targeting rabies, Nipah virus, dengue, SARS or avian influenza. Types of outcomes Primary outcomes: measures: of infection or disease; secondary outcomes: measures of intervention function. Types of studies Original quantitative studies published in English. SEARCH STRATEGY: Databases searched (1980 to 2011): PubMed, CINAHL, ProQuest, EBSCOhost, Web of Science, Science Direct, Cochrane database of systematic reviews, WHOLIS, British Development Library, LILACS, World Bank (East Asia), Asian Development Bank. METHODOLOGICAL QUALITY: Two independent reviewers critically appraised studies using standard Joanna Briggs Institute instruments. Disagreements were resolved through discussion. DATA EXTRACTION: A customised tool was used to extract quantitative data on intervention(s), populations, study methods, and primary and secondary outcomes; and qualitative contextual information or narrative evidence about interventions. DATA SYNTHESIS: Data was synthesised in a narrative summary with the aid of tables. Meta-analysis was used to statistically pool quantitative results. RESULTS: Fifty-seven studies were included. Vector control interventions using copepods, environmental cleanup and education are effective and sustainable at reducing dengue in rural and urban communities, whilst insecticide spraying is effective in urban outbreak situations. Community-based surveillance interventions can effectively identify avian influenza in backyard flocks, but have not been broadly applied. Outbreak control interventions for Nipah virus and SARS are effective but may not be suitable for ongoing control. Canine vaccination and education is more acceptable than culling, but still fails to reach coverage levels required to effectively control rabies. Contextual factors were identified that influence community engagement with, and ultimately effectiveness of, interventions. CONCLUSION: Despite investment in community-based disease control and surveillance in Southeast Asia, published evidence evaluating interventions is limited in quantity and quality. Nonetheless this review identified a number of effective interventions, and several contextual factors influencing effectiveness. Identification of the best programs will require comparative evidence of effectiveness acceptability, cost-effectiveness and sustainability. Implications for practice Interventions are more effective if there are high levels of community ownership and engagement. Linkages between veterinary and public health surveillance systems are essential. Interventions are not well accepted when they fail to acknowledge the importance of animals for economic activity in communities. Implications for research Evidence is needed on functioning and outcomes of current surveillance systems and novel low-cost methods of surveillance. Evaluations of control interventions should control for confounding and report measures of disease, cost and sustainability. Translational research is needed to assess generalisability and evaluate roll-out of effective interventions as regional or national programs.",2013 Feb 12,"['Halton, Kate', 'Sarna, Mohinder', 'Barnett, Adrian', 'Leonardo, Lydia', 'Graves, Nicholas']",JBI Database System Rev Implement Rep,,,True
5738aa0be9b2dd358a1a968f90fad4b0723328f0,PMC,The effect of Allium sativum (Garlic) extract on infectious bronchitis virus in specific pathogen free embryonic egg,,PMC4967842,27516987,NO-CC CODE,"OBJECTIVE: Garlic is a plant has been used as a flavor, and anti-microbial and anti-diarrheal agent. Infectious bronchitis virus (IBV) is a coronavirus. The available vaccines against IBV cannot cover new variants. This study evaluated the inhibitory effects of garlic extract on IBV. MATERIALS AND METHODS: The constituents of garlic extract were detected by gas chromatography. This study was done in four groups of embryonic SPF eggs; first group was used for virus titration; second group received the mixture of different virus titration and constant amount of garlic extract; third group received 10(-3) titration of virus and after 8 hr received garlic extract and the last group received different dilutions of garlic extract. RESULTS: Based on our results, in the second group, IBV vaccine strain (4/91) at all titration and M41 in 10(-2) and 10(-3) titration and in the third group both variants of virus the embryonic Index (EI) was significantly increased. CONCLUSION: The garlic extract had inhibitory effects on IBV in the chickens embryo.",2016 Jul-Aug,"['Mohajer Shojai, Tabassom', 'Ghalyanchi Langeroudi, Arash', 'Karimi, Vahid', 'Barin, Abbas', 'Sadri, Naser']",Avicenna J Phytomed,,,True
e4a3696c1433c42badbd9cce9ec2721be357e02d,PMC,Use of Unamplified RNA/cDNA–Hybrid Nanopore Sequencing for Rapid Detection and Characterization of RNA Viruses,http://dx.doi.org/10.3201/eid2208.160270,PMC4982148,27191483,NO-CC CODE,"Nanopore sequencing, a novel genomics technology, has potential applications for routine biosurveillance, clinical diagnosis, and outbreak investigation of virus infections. Using rapid sequencing of unamplified RNA/cDNA hybrids, we identified Venezuelan equine encephalitis virus and Ebola virus in 3 hours from sample receipt to data acquisition, demonstrating a fieldable technique for RNA virus characterization.",2016 Aug,"['Kilianski, Andy', 'Roth, Pierce A.', 'Liem, Alvin T.', 'Hill, Jessica M.', 'Willis, Kristen L.', 'Rossmaier, Rebecca D.', 'Marinich, Andrew V.', 'Maughan, Michele N.', 'Karavis, Mark A.', 'Kuhn, Jens H.', 'Honko, Anna N.', 'Rosenzweig, C. Nicole']",Emerg Infect Dis,,,True
c6b99ab3de10ff656a6892c41510df092ea76ef4,PMC,Use of Unamplified RNA/cDNA–Hybrid Nanopore Sequencing for Rapid Detection and Characterization of RNA Viruses,http://dx.doi.org/10.3201/eid2208.160270,PMC4982148,27191483,NO-CC CODE,"Nanopore sequencing, a novel genomics technology, has potential applications for routine biosurveillance, clinical diagnosis, and outbreak investigation of virus infections. Using rapid sequencing of unamplified RNA/cDNA hybrids, we identified Venezuelan equine encephalitis virus and Ebola virus in 3 hours from sample receipt to data acquisition, demonstrating a fieldable technique for RNA virus characterization.",2016 Aug,"['Kilianski, Andy', 'Roth, Pierce A.', 'Liem, Alvin T.', 'Hill, Jessica M.', 'Willis, Kristen L.', 'Rossmaier, Rebecca D.', 'Marinich, Andrew V.', 'Maughan, Michele N.', 'Karavis, Mark A.', 'Kuhn, Jens H.', 'Honko, Anna N.', 'Rosenzweig, C. Nicole']",Emerg Infect Dis,,,True
1f9e68c3b98b3ea6a98fbdba8ddbaadd1b2eb018,PMC,"Middle East Respiratory Syndrome Coronavirus Transmission in Extended Family, Saudi Arabia, 2014",http://dx.doi.org/10.3201/eid2208.152015,PMC4982159,27191038,NO-CC CODE,"Risk factors for human-to-human transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) are largely unknown. After MERS-CoV infections occurred in an extended family in Saudi Arabia in 2014, relatives were tested by using real-time reverse transcription PCR (rRT-PCR) and serologic methods. Among 79 relatives, 19 (24%) were MERS-CoV positive; 11 were hospitalized, and 2 died. Eleven (58%) tested positive by rRT-PCR; 8 (42%) tested negative by rRT-PCR but positive by serology. Compared with MERS-CoV–negative adult relatives, MERS-CoV–positive adult relatives were older and more likely to be male and to have chronic medical conditions. Risk factors for household transmission included sleeping in an index patient’s room and touching respiratory secretions from an index patient. Casual contact and simple proximity were not associated with transmission. Serology was more sensitive than standard rRT-PCR for identifying infected relatives, highlighting the value of including serology in future investigations.",2016 Aug,"['Arwady, M. Allison', 'Alraddadi, Basem', 'Basler, Colin', 'Azhar, Esam I.', 'Abuelzein, Eltayb', 'Sindy, Abdulfattah I.', 'Sadiq, Bakr M. Bin', 'Althaqafi, Abdulhakeem O.', 'Shabouni, Omaima', 'Banjar, Ayman', 'Haynes, Lia M.', 'Gerber, Susan I.', 'Feikin, Daniel R.', 'Madani, Tariq A.']",Emerg Infect Dis,,,True
1373fc003367712c4d7def8811c096e4d270274b,PMC,"Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014",http://dx.doi.org/10.3201/eid2208.151949,PMC4982171,27434186,NO-CC CODE,"During August 8, 2014–October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case–control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non–EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis.",2016 Aug,"['Aliabadi, Negar', 'Messacar, Kevin', 'Pastula, Daniel M.', 'Robinson, Christine C.', 'Leshem, Eyal', 'Sejvar, James J.', 'Nix, W. Allan', 'Oberste, M. Steven', 'Feikin, Daniel R.', 'Dominguez, Samuel R.']",Emerg Infect Dis,,,True
ceabb750f6de4f2e3527db125ed62b4528ac958e,PMC,"Toward Developing a Preventive MERS-CoV Vaccine—Report from a Workshop Organized by the Saudi Arabia Ministry of Health and the International Vaccine Institute, Riyadh, Saudi Arabia, November 14–15, 2015",http://dx.doi.org/10.3201/eid2208.160229,PMC4982192,27439020,NO-CC CODE,"Middle East respiratory syndrome (MERS) remains a serious international public health threat. With the goal of accelerating the development of countermeasures against MERS coronavirus (MERS-CoV), funding agencies, nongovernmental organizations, and researchers across the world assembled in Riyadh, Saudi Arabia, on November 14–15, 2015, to discuss vaccine development challenges. The meeting was spearheaded by the Saudi Ministry of Health and co-organized by the International Vaccine Institute, South Korea. Accelerating the development of a preventive vaccine requires a better understanding of MERS epidemiology, transmission, and pathogenesis in humans and animals. A combination of rodent and nonhuman primate models should be considered in evaluating and developing preventive and therapeutic vaccine candidates. Dromedary camels should be considered for the development of veterinary vaccines. Several vaccine technology platforms targeting the MERS-CoV spike protein were discussed. Mechanisms to maximize investment, provide robust data, and affect public health are urgently needed.",2016 Aug,"['Excler, Jean-Louis', 'Delvecchio, Christopher J.', 'Wiley, Ryan E.', 'Williams, Marni', 'Yoon, In-Kyu', 'Modjarrad, Kayvon', 'Boujelal, Mohamed', 'Moorthy, Vasee S.', 'Hersi, Ahmad Salah', 'Kim, Jerome H.', None]",Emerg Infect Dis,,,True
5b4118a71d2dc9dae927ebd17ba9dcaa22f57ce2,PMC,Thin-Section Computed Tomography Manifestations During Convalescence and Long-Term Follow-Up of Patients with Severe Acute Respiratory Syndrome (SARS),http://dx.doi.org/10.12659/MSM.896985,PMC4982531,27501327,NO-CC CODE,"BACKGROUND: SARS is not only an acute disease, but also leads to long-term impaired lung diffusing capacity in some survivors. However, there is a paucity of data regarding long-term CT findings in survivors after SARS. The aim of this study was to assess the changes in lung function and lung thin-section computed tomography (CT) features in patients recovering from severe acute respiratory syndrome (SARS), especially the dynamic changes in ground-glass opacity (GGO). MATERIAL/METHODS: Clinical and radiological data from 11 patients with SARS were collected. The serial follow-up thin-section CTs were evaluated at 3, 6, and 84 months after SARS presentation. The distribution and predominant thin-section CT findings of lesions were evaluated. RESULTS: The extent of the lesions on the CT scans of the 11 patients decreased at 6 and 84 months compared to 3 months. The number of segments involved on 84-month follow-up CTs was less than those at 6 months (P<0.05). The predominant thin-section CT manifestation at 84 months (intralobular and interlobular septal thickening) was different than that at 6 months, at which GGO was predominant. CONCLUSIONS: During convalescence after SARS, GGO and intralobular and interlobular septal thickening were the main thin-section CT manifestation. Intralobular and interlobular septal thickening predominated over GGO at 84 months.",2016 Aug 8,"['Wu, Xiaohua', 'Dong, Dawei', 'Ma, Daqing']",Med Sci Monit,,,True
e776077dcfd93e49990ea94ab5f67e0c02cd3fca,PMC,"The science commons in health research: structure, function, and value",http://dx.doi.org/10.1007/s10961-006-9016-9,PMC4982884,27570367,NO-CC CODE,"The “science commons,” knowledge that is widely accessible at low or no cost, is a uniquely important input to scientific advance and cumulative technological innovation. It is primarily, although not exclusively, funded by government and nonprofit sources. Much of it is produced at academic research centers, although some academic science is proprietary and some privately funded R&D enters the science commons. Science in general aspires to Mertonian norms of openness, universality, objectivity, and critical inquiry. The science commons diverges from proprietary science primarily in being open and being very broadly available. These features make the science commons particularly valuable for advancing knowledge, for training innovators who will ultimately work in both public and private sectors, and in providing a common stock of knowledge upon which all players—both public and private—can draw readily. Open science plays two important roles that proprietary R&D cannot: it enables practical benefits even in the absence of profitable markets for goods and services, and its lays a shared foundation for subsequent private R&D. The history of genomics in the period 1992–2004, covering two periods when genomic startup firms attracted significant private R&D investment, illustrates these features of how a science commons contributes value. Commercial interest in genomics was intense during this period. Fierce competition between private sector and public sector genomics programs was highly visible. Seemingly anomalous behavior, such as private firms funding “open science,” can be explained by unusual business dynamics between established firms wanting to preserve a robust science commons to prevent startup firms from limiting established firms’ freedom to operate. Deliberate policies to create and protect a large science commons were pursued by nonprofit and government funders of genomics research, such as the Wellcome Trust and National Institutes of Health. These policies were crucial to keeping genomic data and research tools widely available at low cost.",2007 Dec 7,"Cook-Deegan, Robert",J Technol Transf,,,True
eb682a5cbe2942e78f0ec4959adce8475d5723d5,PMC,"Transmission dynamics and risk factors for pandemic H1N1‐related illness: outbreak investigation in a rural community of British Columbia, Canada",http://dx.doi.org/10.1111/j.1750-2659.2012.00344.x,PMC4986582,22385647,NO-CC CODE,"Please cite this paper as: Janjua et al. (2012) Transmission dynamics and risk factors for pandemic H1N1‐related illness: outbreak investigation in a rural community of British Columbia, Canada. Influenza and Other Respiratory Viruses 6(3), e54–e62. Objective  To characterize the first‐wave epidemiologic features of influenza‐like illness (ILI) associated with the novel pandemic A/H1N1 [A(H1N1)pdm09] virus. Methods  We used generalized linear mixed models (GLMM) to assess risk factors and non‐parametric and/or parametric distributions to estimate attack rates, secondary attack rates (SAR), duration of illness, and serial interval during a laboratory‐confirmed community outbreak of A(H1N1)pdm09 clustered around on‐reserve residents and households of an elementary school in rural British Columbia, Canada, in late April/early May 2009. ILI details were collected as part of outbreak investigation by community telephone survey in early June 2009. Results  Overall, 92/408 (23%) of participants developed ILI and 36/408 (9%) experienced medically attended ILI (MAILI). The overall SAR in households was 22%: highest among participants 1–4 years of age (yoa) (50%) followed by <1 yoa (38%), 5–8 yoa (20%), 10–19 yoa (13%), 20–49 yoa (20%), and 50–64 yoa (0%). The median serial interval was estimated at 3·5 days (95% CI: 2·1–5·1). In multivariable GLMM analysis, having a chronic condition (OR: 2·58; 95% CI: 1·1–6·04), younger age [1–8 yoa: OR: 4·63; 95% CI: 2·25–9·52; 9–19 yoa: OR: 1·95; 95% CI: 0·97–3·9 (referent: ≥20 yoa)] and receipt of 2008–2009 influenza vaccine (OR: 2·68; 95% CI: 1·37–5·25) were associated with increased risk of ILI. Median duration of illness was 9 days, longer among those with chronic conditions (21 days). Median time to seeking care after developing illness was 4·5 days. On‐reserve participants had higher chronic conditions, household density, ILI, MAILI, and SAR. Conclusions  During a community outbreak of A(H1N1)pdm09‐related illness, we identified substantial clinical ILI attack rates exceeding 20% with secondary household attack rates as high as 50% in young children. The serial interval was short suggesting a narrow period to prevent transmission.",2012 May 2,"['Janjua, Naveed Z.', 'Skowronski, Danuta M.', 'Hottes, Travis S.', 'Osei, William', 'Adams, Evan', 'Petric, Martin', 'Lem, Marcus', 'Tang, Patrick', 'De Serres, Gaston', 'Patrick, David M.', 'Bowering, David']",Influenza Other Respir Viruses,,,True
51ac691426403778f417c61b38f46f85480ca75f,PMC,"Contact Tracing for Imported Case of Middle East Respiratory Syndrome, China, 2015",http://dx.doi.org/10.3201/eid2209.152116,PMC4994337,27532887,NO-CC CODE,Confirmation of an imported case of infection with Middle East respiratory syndrome coronavirus in China triggered intensive contact tracing and mandatory monitoring. Using a hotline and surveillance video footage was effective for tracing all 110 identified contacts. Contact monitoring detected no secondary transmission of infection in China.,2016 Sep,"['Kang, Min', 'Song, Tie', 'Zhong, Haojie', 'Hou, Jie', 'Wang, Jun', 'Li, Jiansen', 'Wu, Jie', 'He, Jianfeng', 'Lin, Jinyan', 'Zhang, Yonghhui']",Emerg Infect Dis,,,True
668d738d46daa0b1a2a32486746d117add1750f5,PMC,"Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia",http://dx.doi.org/10.3201/eid2209.151164,PMC4994343,27532807,NO-CC CODE,"We explored the feasibility of collecting convalescent plasma for passive immunotherapy of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using ELISA to screen serum samples from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed MERS-CoV infection, 230 healthcare workers, and 17 household contacts exposed to MERS-CoV. ELISA-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. Of the 443 tested samples, 12 (2.7%) had a reactive ELISA result, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. Undertaking clinical trials of convalescent plasma for passive immunotherapy of MERS-CoV infection may be feasible, but such trials would be challenging because of the small pool of potential donors with sufficiently high antibody titers. Alternative strategies to identify convalescent plasma donors with adequate antibody titers should be explored, including the sampling of serum from patients with more severe disease and sampling at earlier points during illness.",2016 Sep,"['Arabi, Yaseen M.', 'Hajeer, Ali H.', 'Luke, Thomas', 'Raviprakash, Kanakatte', 'Balkhy, Hanan', 'Johani, Sameera', 'Al-Dawood, Abdulaziz', 'Al-Qahtani, Saad', 'Al-Omari, Awad', 'Al-Hameed, Fahad', 'Hayden, Frederick G.', 'Fowler, Robert', 'Bouchama, Abderrezak', 'Shindo, Nahoko', 'Al-Khairy, Khalid', 'Carson, Gail', 'Taha, Yusri', 'Sadat, Musharaf', 'Alahmadi, Mashail']",Emerg Infect Dis,,,True
6c781ec28811214ca0cb25d34a6569f975139a58,PMC,Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer,http://dx.doi.org/10.1038/nature16988,PMC5018210,26855426,NO-CC CODE,"The tremendous pandemic potential of coronaviruses was demonstrated twice in the last decades by two global outbreaks of deadly pneumonia. Entry of coronaviruses into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer carrying receptor-binding and membrane fusion functions(1). S also contains the principal antigenic determinants and is the target of neutralizing antibodies. Here we present the structure of a murine coronavirus S trimer ectodomain determined at 4.0 Å resolution by single particle cryo-electron microscopy. It reveals the metastable pre-fusion architecture of S and highlights key interactions stabilizing it. The structure shares a common core with paramyxovirus F proteins(2,3), implicating mechanistic similarities and an evolutionary connection between these viral fusion proteins. The accessibility of the highly conserved fusion peptide at the periphery of the trimer indicates potential vaccinology strategies to elicit broadly neutralizing antibodies against coronaviruses. Finally, comparison with crystal structures of human coronavirus S domains allows rationalization of the molecular basis for species specificity based on the use of spatially contiguous but distinct domains.",2016 Mar 3,"['Walls, Alexandra C.', 'Tortorici, M.Alejandra', 'Bosch, Berend-Jan', 'Frenz, Brandon', 'Rottier, Peter J.M.', 'DiMaio, Frank', 'Rey, Félix A.', 'Veesler, David']",Nature,,,True
5a4ba131e69f16674cc368d8bdaf7f69f6806e20,PMC,Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer,http://dx.doi.org/10.1038/nature16988,PMC5018210,26855426,NO-CC CODE,"The tremendous pandemic potential of coronaviruses was demonstrated twice in the last decades by two global outbreaks of deadly pneumonia. Entry of coronaviruses into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer carrying receptor-binding and membrane fusion functions(1). S also contains the principal antigenic determinants and is the target of neutralizing antibodies. Here we present the structure of a murine coronavirus S trimer ectodomain determined at 4.0 Å resolution by single particle cryo-electron microscopy. It reveals the metastable pre-fusion architecture of S and highlights key interactions stabilizing it. The structure shares a common core with paramyxovirus F proteins(2,3), implicating mechanistic similarities and an evolutionary connection between these viral fusion proteins. The accessibility of the highly conserved fusion peptide at the periphery of the trimer indicates potential vaccinology strategies to elicit broadly neutralizing antibodies against coronaviruses. Finally, comparison with crystal structures of human coronavirus S domains allows rationalization of the molecular basis for species specificity based on the use of spatially contiguous but distinct domains.",2016 Mar 3,"['Walls, Alexandra C.', 'Tortorici, M.Alejandra', 'Bosch, Berend-Jan', 'Frenz, Brandon', 'Rottier, Peter J.M.', 'DiMaio, Frank', 'Rey, Félix A.', 'Veesler, David']",Nature,,,False
5bcf7ccf893d6ed530a6b6c779c90babbdf6e3bc,PMC,Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer,http://dx.doi.org/10.1038/nature16988,PMC5018210,26855426,NO-CC CODE,"The tremendous pandemic potential of coronaviruses was demonstrated twice in the last decades by two global outbreaks of deadly pneumonia. Entry of coronaviruses into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer carrying receptor-binding and membrane fusion functions(1). S also contains the principal antigenic determinants and is the target of neutralizing antibodies. Here we present the structure of a murine coronavirus S trimer ectodomain determined at 4.0 Å resolution by single particle cryo-electron microscopy. It reveals the metastable pre-fusion architecture of S and highlights key interactions stabilizing it. The structure shares a common core with paramyxovirus F proteins(2,3), implicating mechanistic similarities and an evolutionary connection between these viral fusion proteins. The accessibility of the highly conserved fusion peptide at the periphery of the trimer indicates potential vaccinology strategies to elicit broadly neutralizing antibodies against coronaviruses. Finally, comparison with crystal structures of human coronavirus S domains allows rationalization of the molecular basis for species specificity based on the use of spatially contiguous but distinct domains.",2016 Mar 3,"['Walls, Alexandra C.', 'Tortorici, M.Alejandra', 'Bosch, Berend-Jan', 'Frenz, Brandon', 'Rottier, Peter J.M.', 'DiMaio, Frank', 'Rey, Félix A.', 'Veesler, David']",Nature,,,False
57d82101cbebfe51ba2cebdc3e20c438cfabe484,PMC,Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer,http://dx.doi.org/10.1038/nature16988,PMC5018210,26855426,NO-CC CODE,"The tremendous pandemic potential of coronaviruses was demonstrated twice in the last decades by two global outbreaks of deadly pneumonia. Entry of coronaviruses into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer carrying receptor-binding and membrane fusion functions(1). S also contains the principal antigenic determinants and is the target of neutralizing antibodies. Here we present the structure of a murine coronavirus S trimer ectodomain determined at 4.0 Å resolution by single particle cryo-electron microscopy. It reveals the metastable pre-fusion architecture of S and highlights key interactions stabilizing it. The structure shares a common core with paramyxovirus F proteins(2,3), implicating mechanistic similarities and an evolutionary connection between these viral fusion proteins. The accessibility of the highly conserved fusion peptide at the periphery of the trimer indicates potential vaccinology strategies to elicit broadly neutralizing antibodies against coronaviruses. Finally, comparison with crystal structures of human coronavirus S domains allows rationalization of the molecular basis for species specificity based on the use of spatially contiguous but distinct domains.",2016 Mar 3,"['Walls, Alexandra C.', 'Tortorici, M.Alejandra', 'Bosch, Berend-Jan', 'Frenz, Brandon', 'Rottier, Peter J.M.', 'DiMaio, Frank', 'Rey, Félix A.', 'Veesler, David']",Nature,,,False
cd492bb5d19539c9666aaa080e941f1e6e35f923,PMC,Aptamers against pathogenic microorganisms,http://dx.doi.org/10.3109/1040841X.2015.1070115,PMC5022137,26258445,NO-CC CODE,"An important current issue of modern molecular medicine and biotechnology is the search for new approaches to early diagnostic assays and adequate therapy of infectious diseases. One of the promising solutions to this problem might be a development of nucleic acid aptamers capable of interacting specifically with bacteria, protozoa, and viruses. Such aptamers can be used for the specific recognition of infectious agents as well as for blocking of their functions. The present review summarizes various modern SELEX techniques used in this field, and of several currently identified aptamers against viral particles and unicellular organisms, and their applications. The prospects of applying nucleic acid aptamers for the development of novel detection systems and antibacterial and antiviral drugs are discussed.",2016 Nov 1,"['Davydova, Anna', 'Vorobjeva, Maria', 'Pyshnyi, Dmitrii', 'Altman, Sidney', 'Vlassov, Valentin', 'Venyaminova, Alya']",Crit Rev Microbiol,,,True
ff365ebbc0fc55476886b0abd129e227c1f8a527,PMC,Blood metal ion levels are not a useful test for adverse reactions to metal debris: A systematic review and meta-analysis,http://dx.doi.org/10.1302/2046-3758.59.BJR-2016-0027.R1,PMC5027892,27612918,NO-CC CODE,"OBJECTIVES: Alarm over the reported high failure rates for metal-on-metal (MoM) hip implants as well as their potential for locally aggressive Adverse Reactions to Metal Debris (ARMDs) has prompted government agencies, internationally, to recommend the monitoring of patients with MoM hip implants. Some have advised that a blood ion level >7 µg/L indicates potential for ARMDs. We report a systematic review and meta-analysis of the performance of metal ion testing for ARMDs. METHODS: We searched MEDLINE and EMBASE to identify articles from which it was possible to reconstruct a 2 × 2 table. Two readers independently reviewed all articles and extracted data using explicit criteria. We computed a summary receiver operating curve using a Bayesian random-effects hierarchical model. RESULTS: Our literature search returned 575 unique articles; only six met inclusion criteria defined a priori. The discriminative capacity of ion tests was homogeneous across studies but that there was substantial cut-point heterogeneity. Our best estimate of the “true” area under curve (AUC) for metal ion testing is 0.615, with a 95% credible interval of 0.480 to 0.735, thus we can state that the probability that metal ion testing is actually clinically useful with an AUC ≥ 0.75 is 1.7%. CONCLUSION: Metal ion levels are not useful as a screening test for identifying high risk patients because ion testing will either lead to a large burden of false positive patients, or otherwise marginally modify the pre-test probability. With the availability of more accurate non-invasive tests, we did not find any evidence for using blood ion levels to diagnose symptomatic patients. Cite this article: M. Pahuta, J. M. Smolders, J. L. van Susante, J. Peck, P. R. Kim, P. E. Beaule. Blood metal ion levels are not a useful test for adverse reactions to metal debris: a systematic review and meta-analysis. Bone Joint Res 2016;5:379–386. DOI: 10.1302/2046-3758.59.BJR-2016-0027.R1.",2016 Sep 9,"['Pahuta, M.', 'Smolders, J. M.', 'van Susante, J. L.', 'Peck, J.', 'Kim, P. R.', 'Beaule, P. E.']",Bone Joint Res,,,True
30cde71f98e1b4202ba43473e686ec4b5b23d42f,PMC,A Single-Cell Platform for Monitoring Viral Proteolytic Cleavage in Different Cellular Compartments,http://dx.doi.org/10.4137/BCI.S30379,PMC5034881,27688710,NO-CC CODE,"Infectious diseases affect human health despite advances in biomedical research and drug discovery. Among these, viruses are especially difficult to tackle due to the sudden transfer from animals to humans, high mutational rates, resistance to current treatments, and the intricacies of their molecular interactions with the host. As an example of these interactions, we describe a cell-based approach to monitor specific proteolytic events executed by either the viral-encoded protease or by host proteins on the virus. We then emphasize the significance of examining proteolysis within the subcellular compartment where cleavage occurs naturally. We show the power of stable expression, highlighting the usefulness of the cell-based multiplexed approach, which we have adapted to two independent assays previously developed to monitor (a) the activity of the HIV-1-encoded protease or (b) the cleavage of the HIV-1-encoded envelope protein by the host. Multiplexing was achieved by mixing cells each carrying a different assay or, alternatively, by engineering cells expressing two assays. Multiplexing relies on the robustness of the individual assays and their clear discrimination, further enhancing screening capabilities in an attempt to block proteolytic events required for viral infectivity and spread.",2016 Sep 22,"['Abbadessa, Darin', 'Smurthwaite, Cameron A.', 'Reed, Connor W.', 'Wolkowicz, Roland']",Biochem Insights,,,True
01732214b0e66594afaceb2f641102b42e1b4685,PMC,"Global Capacity for Emerging Infectious Disease Detection, 1996–2014",http://dx.doi.org/10.3201/eid2210.151956,PMC5038396,27649306,NO-CC CODE,"The speed with which disease outbreaks are recognized is critical for establishing effective control efforts. We evaluate global improvements in the timeliness of outbreak discovery and communication during 2010–2014 as a follow-up to a 2010 report. For all outbreaks reported by the World Health Organization’s Disease Outbreak News, we estimate the number of days from first symptoms until outbreak discovery and until first public communication. We report median discovery and communication delays overall, by region, and by Human Development Index (HDI) quartile. We use Cox proportional hazards regression to assess changes in these 2 outcomes over time, along with Loess curves for visualization. Improvement since 1996 was greatest in the Eastern Mediterranean and Western Pacific regions and in countries in the middle HDI quartiles. However, little progress has occurred since 2010. Further improvements in surveillance will likely require additional international collaboration with a focus on regions of low or unstable HDI.",2016 Oct,"['Kluberg, Sheryl A.', 'Mekaru, Sumiko R.', 'McIver, David J.', 'Madoff, Lawrence C.', 'Crawley, Adam W.', 'Smolinski, Mark S.', 'Brownstein, John S.']",Emerg Infect Dis,,,True
f660fc62642dc8cdac853e68b3d2427fc967a361,PMC,Viral RNA in Blood as Indicator of Severe Outcome in Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.3201/eid2210.160218,PMC5038397,27479636,NO-CC CODE,"We evaluated the diagnostic and clinical usefulness of blood specimens to detect Middle East respiratory syndrome coronavirus infection in 21 patients from the 2015 outbreak in South Korea. Viral RNA was detected in blood from 33% of patients at initial diagnosis, and the detection preceded a worse clinical course.",2016 Oct,"['Kim, So Yeon', 'Park, Sun Jae', 'Cho, Sook Young', 'Cha, Ran-hui', 'Jee, Hyeon-Gun', 'Kim, Gayeon', 'Shin, Hyoung-Shik', 'Kim, Yeonjae', 'Jung, Yu Mi', 'Yang, Jeong-Sun', 'Kim, Sung Soon', 'Cho, Sung Im', 'Kim, Man Jin', 'Lee, Jee-Soo', 'Lee, Seung Jun', 'Seo, Soo Hyun', 'Park, Sung Sup', 'Seong, Moon-Woo']",Emerg Infect Dis,,,True
f00de2c951d24161cd4c46613650ceeded00167a,PMC,Viral RNA in Blood as Indicator of Severe Outcome in Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.3201/eid2210.160218,PMC5038397,27479636,NO-CC CODE,"We evaluated the diagnostic and clinical usefulness of blood specimens to detect Middle East respiratory syndrome coronavirus infection in 21 patients from the 2015 outbreak in South Korea. Viral RNA was detected in blood from 33% of patients at initial diagnosis, and the detection preceded a worse clinical course.",2016 Oct,"['Kim, So Yeon', 'Park, Sun Jae', 'Cho, Sook Young', 'Cha, Ran-hui', 'Jee, Hyeon-Gun', 'Kim, Gayeon', 'Shin, Hyoung-Shik', 'Kim, Yeonjae', 'Jung, Yu Mi', 'Yang, Jeong-Sun', 'Kim, Sung Soon', 'Cho, Sung Im', 'Kim, Man Jin', 'Lee, Jee-Soo', 'Lee, Seung Jun', 'Seo, Soo Hyun', 'Park, Sung Sup', 'Seong, Moon-Woo']",Emerg Infect Dis,,,False
a7c3c93984700518a2a04aeb492df3c1a2277467,PMC,Pandemic,http://dx.doi.org/10.3201/eid2210.160795,PMC5038412,,NO-CC CODE,,2016 Oct,"Nuzzo, Jennifer B.",Emerg Infect Dis,,,False
6ea2f62005558ec8368cecfec61be9635aab6410,PMC,Persistence of Antibodies against Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.3201/eid2210.160706,PMC5038413,27332149,NO-CC CODE,"To determine how long antibodies against Middle East respiratory syndrome coronavirus persist, we measured long-term antibody responses among persons serologically positive or indeterminate after a 2012 outbreak in Jordan. Antibodies, including neutralizing antibodies, were detectable in 6 (86%) of 7 persons for at least 34 months after the outbreak.",2016 Oct,"['Payne, Daniel C.', 'Iblan, Ibrahim', 'Rha, Brian', 'Alqasrawi, Sultan', 'Haddadin, Aktham', 'Al Nsour, Mohannad', 'Alsanouri, Tarek', 'Ali, Sami Sheikh', 'Harcourt, Jennifer', 'Miao, Congrong', 'Tamin, Azaibi', 'Gerber, Susan I.', 'Haynes, Lia M.', 'Al Abdallat, Mohammad Mousa']",Emerg Infect Dis,,,True
d90a211ef31ec56091a8c30bb8ee39e9f07ca755,PMC,"Estimation of Severe Middle East Respiratory Syndrome Cases in the Middle East, 2012–2016",http://dx.doi.org/10.3201/eid2210.151121,PMC5038414,27648640,NO-CC CODE,"Using data from travelers to 4 countries in the Middle East, we estimated 3,250 (95% CI 1,300–6,600) severe cases of Middle East respiratory syndrome occurred in this region during September 2012–January 2016. This number is 2.3-fold higher than the number of laboratory-confirmed cases recorded in these countries.",2016 Oct,"['O’Hagan, Justin J.', 'Carias, Cristina', 'Rudd, Jessica M.', 'Pham, Huong T.', 'Haber, Yonat', 'Pesik, Nicki', 'Cetron, Martin S.', 'Gambhir, Manoj', 'Gerber, Susan I.', 'Swerdlow, David L.']",Emerg Infect Dis,,,True
129385d837be59df19fab81b392563d1202ae5d1,PMC,"Estimation of Severe Middle East Respiratory Syndrome Cases in the Middle East, 2012–2016",http://dx.doi.org/10.3201/eid2210.151121,PMC5038414,27648640,NO-CC CODE,"Using data from travelers to 4 countries in the Middle East, we estimated 3,250 (95% CI 1,300–6,600) severe cases of Middle East respiratory syndrome occurred in this region during September 2012–January 2016. This number is 2.3-fold higher than the number of laboratory-confirmed cases recorded in these countries.",2016 Oct,"['O’Hagan, Justin J.', 'Carias, Cristina', 'Rudd, Jessica M.', 'Pham, Huong T.', 'Haber, Yonat', 'Pesik, Nicki', 'Cetron, Martin S.', 'Gambhir, Manoj', 'Gerber, Susan I.', 'Swerdlow, David L.']",Emerg Infect Dis,,,True
cf085d7780e024e54db7c45b4ca64900e5713a5e,PMC,National Institutes of Health–Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities,http://dx.doi.org/10.2337/db16-0234,PMC5079635,27465220,NO-CC CODE,"Eight manufacturing facilities participating in the National Institutes of Health–sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects with type 1 diabetes. Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis, and test methods. The process was compliant with Current Good Manufacturing Practices and Current Good Tissue Practices. This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results, including lot release. The results demonstrate the feasibility of implementing a harmonized process at multiple facilities for the manufacture of a complex cellular product. The quality systems and regulatory and operational strategies developed by the CIT Consortium yielded product lots that met the prespecified characteristics of safety, purity, potency, and identity and were successfully transplanted into 48 subjects. No adverse events attributable to the product and no cases of primary nonfunction were observed.",2016 Nov 27,"['Ricordi, Camillo', 'Goldstein, Julia S.', 'Balamurugan, A.N.', 'Szot, Gregory L.', 'Kin, Tatsuya', 'Liu, Chengyang', 'Czarniecki, Christine W.', 'Barbaro, Barbara', 'Bridges, Nancy D.', 'Cano, Jose', 'Clarke, William R.', 'Eggerman, Thomas L.', 'Hunsicker, Lawrence G.', 'Kaufman, Dixon B.', 'Khan, Aisha', 'Lafontant, David-Erick', 'Linetsky, Elina', 'Luo, Xunrong', 'Markmann, James F.', 'Naji, Ali', 'Korsgren, Olle', 'Oberholzer, Jose', 'Turgeon, Nicole A.', 'Brandhorst, Daniel', 'Chen, Xiaojuan', 'Friberg, Andrew S.', 'Lei, Ji', 'Wang, Ling-jia', 'Wilhelm, Joshua J.', 'Willits, Jamie', 'Zhang, Xiaomin', 'Hering, Bernhard J.', 'Posselt, Andrew M.', 'Stock, Peter G.', 'Shapiro, A.M. James']",Diabetes,,,True
0ad01da34afb0c735d7d9e50ca27610651b81d6e,PMC,"Exposures among MERS Case-Patients, Saudi Arabia, January–February 2016",http://dx.doi.org/10.3201/eid2211.161042,PMC5088020,27606432,NO-CC CODE,,2016 Nov,"['Alhakeem, Raafat F.', 'Midgley, Claire M.', 'Assiri, Abdullah M.', 'Alessa, Mohammed', 'Al Hawaj, Hassan', 'Saeed, Abdulaziz Bin', 'Almasri, Malak M.', 'Lu, Xiaoyan', 'Abedi, Glen R.', 'Abdalla, Osman', 'Mohammed, Mutaz', 'Algarni, Homoud S.', 'Al-Abdely, Hail M.', 'Alsharef, Ali Abraheem', 'Nooh, Randa', 'Erdman, Dean D.', 'Gerber, Susan I.', 'Watson, John T.']",Emerg Infect Dis,,,True
8c15e0d2ead3c4f2f977bff7c4c54aeefbb90872,PMC,"Exposures among MERS Case-Patients, Saudi Arabia, January–February 2016",http://dx.doi.org/10.3201/eid2211.161042,PMC5088020,27606432,NO-CC CODE,,2016 Nov,"['Alhakeem, Raafat F.', 'Midgley, Claire M.', 'Assiri, Abdullah M.', 'Alessa, Mohammed', 'Al Hawaj, Hassan', 'Saeed, Abdulaziz Bin', 'Almasri, Malak M.', 'Lu, Xiaoyan', 'Abedi, Glen R.', 'Abdalla, Osman', 'Mohammed, Mutaz', 'Algarni, Homoud S.', 'Al-Abdely, Hail M.', 'Alsharef, Ali Abraheem', 'Nooh, Randa', 'Erdman, Dean D.', 'Gerber, Susan I.', 'Watson, John T.']",Emerg Infect Dis,,,False
a829488e75a4af749d8fc997fcf24ebeb907228b,PMC,Risk Factors for Middle East Respiratory Syndrome Coronavirus Infection among Healthcare Personnel,http://dx.doi.org/10.3201/eid2211.160920,PMC5088034,27767011,NO-CC CODE,"Healthcare settings can amplify transmission of Middle East respiratory syndrome coronavirus (MERS-CoV), but knowledge gaps about the epidemiology of transmission remain. We conducted a retrospective cohort study among healthcare personnel in hospital units that treated MERS-CoV patients. Participants were interviewed about exposures to MERS-CoV patients, use of personal protective equipment, and signs and symptoms of illness after exposure. Infection status was determined by the presence of antibodies against MERS-CoV. To assess risk factors, we compared infected and uninfected participants. Healthcare personnel caring for MERS-CoV patients were at high risk for infection, but infection most often resulted in a relatively mild illness that might be unrecognized. In the healthcare personnel cohort reported here, infections occurred exclusively among those who had close contact with MERS-CoV patients.",2016 Nov,"['Alraddadi, Basem M.', 'Al-Salmi, Hanadi S.', 'Jacobs-Slifka, Kara', 'Slayton, Rachel B.', 'Estivariz, Concepcion F.', 'Geller, Andrew I.', 'Al-Turkistani, Hanan H.', 'Al-Rehily, Sanaa S.', 'Alserehi, Haleema A.', 'Wali, Ghassan Y.', 'Alshukairi, Abeer N.', 'Azhar, Esam I.', 'Haynes, Lia', 'Swerdlow, David L.', 'Jernigan, John A.', 'Madani, Tariq A.']",Emerg Infect Dis,,,True
0843b669142963c77ba252334d8bba1d78abbc12,PMC,A Simple Sketch Symbolizing Self-Reliance,http://dx.doi.org/10.3201/eid2211.AC2211,PMC5088038,,NO-CC CODE,,2016 Nov,"Breedlove, Byron",Emerg Infect Dis,,,True
d24c57228f54ec5f1ac1f075a265eff7b80b8b71,PMC,"Lack of Mimivirus Detection in Patients with Respiratory Disease, China",http://dx.doi.org/10.3201/eid2211.160687,PMC5088041,27331870,NO-CC CODE,,2016 Nov,"['Zhang, Xiao-Ai', 'Zhu, Teng', 'Zhang, Pan-He', 'Li, Hao', 'Li, Yan', 'Liu, En-Mei', 'Liu, Wei', 'Cao, Wu-Chun']",Emerg Infect Dis,,,True
9da34b54546112d418aa2b0e1ea55758b456a54c,PMC,Nanoyeast and Other Cell Envelope Compositions for Protein Studies and Biosensor Applications,http://dx.doi.org/10.1021/acsami.6b09263,PMC5114700,27762541,NO-CC CODE,"[Image: see text] Rapid progress in disease biomarker discovery has increased the need for robust detection technologies. In the past several years, the designs of many immunoaffinity reagents have focused on lowering costs and improving specificity while also promoting stability. Antibody fragments (scFvs) have long been displayed on the surface of yeast and phage libraries for selection; however, the stable production of such fragments presents challenges that hamper their widespread use in diagnostics. Membrane and cell wall proteins similarly suffer from stability problems when solubilized from their native environment. Recently, cell envelope compositions that maintain membrane proteins in native or native-like lipid environment to improve their stability have been developed. This cell envelope composition approach has now been adapted toward stabilizing antibody fragments by retaining their native cell wall environment. A new class of immunoaffinity reagents has been developed that maintains antibody fragment attachment to yeast cell wall. Herein, we review recent strategies that incorporate cell wall fragments with functional scFvs, which are designed for easy production while maintaining specificity and stability when in use with simple detection platforms. These cell wall based antibody fragments are globular in structure, and heterogeneous in size, with fragments ranging from tens to hundreds of nanometers in size. These fragments appear to retain activity once immobilized onto biosensor surfaces for the specific and sensitive detection of pathogen antigens. They can be quickly and economically generated from a yeast display library and stored lyophilized, at room temperature, for up to a year with little effect on stability. This new format of scFvs provides stability, in a simple and low-cost manner toward the use of scFvs in biosensor applications. The production and “panning” of such antibody cell wall composites are also extremely facile, enabling the rapid adoption of stable and inexpensive affinity reagents for emerging infectious threats.",2016 Nov 16,"['Grewal, Yadveer\nS.', 'Shiddiky, Muhammad J. A.', 'Mahler, Stephen M.', 'Cangelosi, Gerard A.', 'Trau, Matt']",ACS Appl Mater Interfaces,,,True
e3af2ca43010f59c3d1bb731abd011e3dd0fc51c,PMC,Date of origin of the SARS coronavirus strains,http://dx.doi.org/10.1186/1471-2334-4-3,PMC516801,15028113,NO-CC CODE,"BACKGROUND: A new respiratory infectious epidemic, severe acute respiratory syndrome (SARS), broke out and spread throughout the world. By now the putative pathogen of SARS has been identified as a new coronavirus, a single positive-strand RNA virus. RNA viruses commonly have a high rate of genetic mutation. It is therefore important to know the mutation rate of the SARS coronavirus as it spreads through the population. Moreover, finding a date for the last common ancestor of SARS coronavirus strains would be useful for understanding the circumstances surrounding the emergence of the SARS pandemic and the rate at which SARS coronavirus diverge. METHODS: We propose a mathematical model to estimate the evolution rate of the SARS coronavirus genome and the time of the last common ancestor of the sequenced SARS strains. Under some common assumptions and justifiable simplifications, a few simple equations incorporating the evolution rate (K) and time of the last common ancestor of the strains (T(0)) can be deduced. We then implemented the least square method to estimate K and T(0 )from the dataset of sequences and corresponding times. Monte Carlo stimulation was employed to discuss the results. RESULTS: Based on 6 strains with accurate dates of host death, we estimated the time of the last common ancestor to be about August or September 2002, and the evolution rate to be about 0.16 base/day, that is, the SARS coronavirus would on average change a base every seven days. We validated our method by dividing the strains into two groups, which coincided with the results from comparative genomics. CONCLUSION: The applied method is simple to implement and avoid the difficulty and subjectivity of choosing the root of phylogenetic tree. Based on 6 strains with accurate date of host death, we estimated a time of the last common ancestor, which is coincident with epidemic investigations, and an evolution rate in the same range as that reported for the HIV-1 virus.",2004 Feb 6,"['Lu, Hongchao', 'Zhao, Yi', 'Zhang, Jingfen', 'Wang, Yuelan', 'Li, Wei', 'Zhu, Xiaopeng', 'Sun, Shiwei', 'Xu, Jingyi', 'Ling, Lunjiang', 'Cai, Lun', 'Bu, Dongbo', 'Chen, Runsheng']",BMC Infect Dis,,,True
d07a12c15f26f94f6b1d0fc1ab61730140e8c7d2,PMC,A small stem-loop structure of the Ebola virus trailer is essential for replication and interacts with heat-shock protein A8,http://dx.doi.org/10.1093/nar/gkw825,PMC5175359,27651462,NO-CC CODE,"Ebola virus (EBOV) is a single-stranded negative-sense RNA virus belonging to the Filoviridae family. The leader and trailer non-coding regions of the EBOV genome likely regulate its transcription, replication, and progeny genome packaging. We investigated the cis-acting RNA signals involved in RNA–RNA and RNA–protein interactions that regulate replication of eGFP-encoding EBOV minigenomic RNA and identified heat shock cognate protein family A (HSC70) member 8 (HSPA8) as an EBOV trailer-interacting host protein. Mutational analysis of the trailer HSPA8 binding motif revealed that this interaction is essential for EBOV minigenome replication. Selective 2′-hydroxyl acylation analyzed by primer extension analysis of the secondary structure of the EBOV minigenomic RNA indicates formation of a small stem-loop composed of the HSPA8 motif, a 3′ stem-loop (nucleotides 1868–1890) that is similar to a previously identified structure in the replicative intermediate (RI) RNA and a panhandle domain involving a trailer-to-leader interaction. Results of minigenome assays and an EBOV reverse genetic system rescue support a role for both the panhandle domain and HSPA8 motif 1 in virus replication.",2016 Nov 16,"['Sztuba-Solinska, Joanna', 'Diaz, Larissa', 'Kumar, Mia R.', 'Kolb, Gaëlle', 'Wiley, Michael R.', 'Jozwick, Lucas', 'Kuhn, Jens H.', 'Palacios, Gustavo', 'Radoshitzky, Sheli R.', 'J.\xa0Le\xa0Grice, Stuart F.', 'Johnson, Reed F.']",Nucleic Acids Res,,,True
c3bb7beb561c6fd26079db11c0af1aaed7ada4c0,PMC,A small stem-loop structure of the Ebola virus trailer is essential for replication and interacts with heat-shock protein A8,http://dx.doi.org/10.1093/nar/gkw825,PMC5175359,27651462,NO-CC CODE,"Ebola virus (EBOV) is a single-stranded negative-sense RNA virus belonging to the Filoviridae family. The leader and trailer non-coding regions of the EBOV genome likely regulate its transcription, replication, and progeny genome packaging. We investigated the cis-acting RNA signals involved in RNA–RNA and RNA–protein interactions that regulate replication of eGFP-encoding EBOV minigenomic RNA and identified heat shock cognate protein family A (HSC70) member 8 (HSPA8) as an EBOV trailer-interacting host protein. Mutational analysis of the trailer HSPA8 binding motif revealed that this interaction is essential for EBOV minigenome replication. Selective 2′-hydroxyl acylation analyzed by primer extension analysis of the secondary structure of the EBOV minigenomic RNA indicates formation of a small stem-loop composed of the HSPA8 motif, a 3′ stem-loop (nucleotides 1868–1890) that is similar to a previously identified structure in the replicative intermediate (RI) RNA and a panhandle domain involving a trailer-to-leader interaction. Results of minigenome assays and an EBOV reverse genetic system rescue support a role for both the panhandle domain and HSPA8 motif 1 in virus replication.",2016 Nov 16,"['Sztuba-Solinska, Joanna', 'Diaz, Larissa', 'Kumar, Mia R.', 'Kolb, Gaëlle', 'Wiley, Michael R.', 'Jozwick, Lucas', 'Kuhn, Jens H.', 'Palacios, Gustavo', 'Radoshitzky, Sheli R.', 'J.\xa0Le\xa0Grice, Stuart F.', 'Johnson, Reed F.']",Nucleic Acids Res,,,False
693101049b23404d0ea907223cdcd0777fcc604c,PMC,Norovirus Infection in Harbor Porpoises,http://dx.doi.org/10.3201/eid2301.161081,PMC5176230,27983498,NO-CC CODE,"A norovirus was detected in harbor porpoises, a previously unknown host for norovirus. This norovirus had low similarity to any known norovirus. Viral RNA was detected primarily in intestinal tissue, and specific serum antibodies were detected in 8 (24%) of 34 harbor porpoises from the North Sea.",2017 Jan,"['de Graaf, Miranda', 'Bodewes, Rogier', 'van Elk, Cornelis E.', 'van de Bildt, Marco', 'Getu, Sarah', 'Aron, Georgina I.', 'Verjans, Georges M.G.M.', 'Osterhaus, Albert D.M.E.', 'van den Brand, Judith M.A.', 'Kuiken, Thijs', 'Koopmans, Marion P.G.']",Emerg Infect Dis,,,True
5fb8313680176593b75962be3d056a07c4d31538,PMC,Norovirus Infection in Harbor Porpoises,http://dx.doi.org/10.3201/eid2301.161081,PMC5176230,27983498,NO-CC CODE,"A norovirus was detected in harbor porpoises, a previously unknown host for norovirus. This norovirus had low similarity to any known norovirus. Viral RNA was detected primarily in intestinal tissue, and specific serum antibodies were detected in 8 (24%) of 34 harbor porpoises from the North Sea.",2017 Jan,"['de Graaf, Miranda', 'Bodewes, Rogier', 'van Elk, Cornelis E.', 'van de Bildt, Marco', 'Getu, Sarah', 'Aron, Georgina I.', 'Verjans, Georges M.G.M.', 'Osterhaus, Albert D.M.E.', 'van den Brand, Judith M.A.', 'Kuiken, Thijs', 'Koopmans, Marion P.G.']",Emerg Infect Dis,,,True
3a6f606e9489f6f9ae05e6f0a5fec50572fd0208,PMC,"Upsurge of Enterovirus D68, the Netherlands, 2016",http://dx.doi.org/10.3201/eid2301.161313,PMC5176244,27660916,NO-CC CODE,"In June and July 2016, we identified 8 adults and 17 children with respiratory enterovirus D68 infections. Thirteen children required intensive care unit admission because of respiratory insufficiency, and 1 had concomitant acute flaccid myelitis. Phylogenetic analysis showed that all of 20 sequences obtained belong to the recently described clade B3.",2017 Jan,"['Knoester, Marjolein', 'Schölvinck, Elisabeth H.', 'Poelman, Randy', 'Smit, Sylvia', 'Vermont, Clementien L.', 'Niesters, Hubert G.M.', 'Van Leer-Buter, Coretta C.']",Emerg Infect Dis,,,True
869d3d4d00795e9ca42618b9207f6dd315b19cd3,PMC,Assessing the Epidemic Potential of RNA and DNA Viruses,http://dx.doi.org/10.3201/eid2212.160123,PMC5189130,27869592,NO-CC CODE,"Many new and emerging RNA and DNA viruses are zoonotic or have zoonotic origins in an animal reservoir that is usually mammalian and sometimes avian. Not all zoonotic viruses are transmissible (directly or by an arthropod vector) between human hosts. Virus genome sequence data provide the best evidence of transmission. Of human transmissible virus, 37 species have so far been restricted to self-limiting outbreaks. These viruses are priorities for surveillance because relatively minor changes in their epidemiologies can potentially lead to major changes in the threat they pose to public health. On the basis of comparisons across all recognized human viruses, we consider the characteristics of these priority viruses and assess the likelihood that they will further emerge in human populations. We also assess the likelihood that a virus that can infect humans but is not capable of transmission (directly or by a vector) between human hosts can acquire that capability.",2016 Dec,"['Woolhouse, Mark E.J.', 'Brierley, Liam', 'McCaffery, Chris', 'Lycett, Sam']",Emerg Infect Dis,,,True
4546489385a109b082c9a09c3a0faf7788faa6e6,PMC,Assessing the Epidemic Potential of RNA and DNA Viruses,http://dx.doi.org/10.3201/eid2212.160123,PMC5189130,27869592,NO-CC CODE,"Many new and emerging RNA and DNA viruses are zoonotic or have zoonotic origins in an animal reservoir that is usually mammalian and sometimes avian. Not all zoonotic viruses are transmissible (directly or by an arthropod vector) between human hosts. Virus genome sequence data provide the best evidence of transmission. Of human transmissible virus, 37 species have so far been restricted to self-limiting outbreaks. These viruses are priorities for surveillance because relatively minor changes in their epidemiologies can potentially lead to major changes in the threat they pose to public health. On the basis of comparisons across all recognized human viruses, we consider the characteristics of these priority viruses and assess the likelihood that they will further emerge in human populations. We also assess the likelihood that a virus that can infect humans but is not capable of transmission (directly or by a vector) between human hosts can acquire that capability.",2016 Dec,"['Woolhouse, Mark E.J.', 'Brierley, Liam', 'McCaffery, Chris', 'Lycett, Sam']",Emerg Infect Dis,,,False
925b804acc0847b8811aecbda567350372b3254f,PMC,Time Course of MERS-CoV Infection and Immunity in Dromedary Camels,http://dx.doi.org/10.3201/eid2212.160382,PMC5189137,27224315,NO-CC CODE,"Knowledge about immunity to Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels is essential for infection control and vaccination. A longitudinal study of 11 dam–calf pairs showed that calves lose maternal MERS-CoV antibodies 5–6 months postparturition and are left susceptible to infection, indicating a short window of opportunity for vaccination.",2016 Dec,"['Meyer, Benjamin', 'Juhasz, Judit', 'Barua, Rajib', 'Das Gupta, Aungshuman', 'Hakimuddin, Fatima', 'Corman, Victor M.', 'Müller, Marcel A.', 'Wernery, Ulrich', 'Drosten, Christian', 'Nagy, Peter']",Emerg Infect Dis,,,True
e58c8d02a519cb271727a06b0b54ea39307cf9f8,PMC,"New Hepatitis E Virus Genotype in Bactrian Camels, Xinjiang, China, 2013",http://dx.doi.org/10.3201/eid2212.160979,PMC5189163,27869607,NO-CC CODE,,2016 Dec,"['Woo, Patrick C.Y.', 'Lau, Susanna K.P.', 'Teng, Jade L.L.', 'Cao, Kai-Yuan', 'Wernery, Ulrich', 'Schountz, Tony', 'Chiu, Tsz Ho', 'Tsang, Alan K.L.', 'Wong, Po-Chun', 'Wong, Emily Y.M.', 'Yuen, Kwok-Yung']",Emerg Infect Dis,,,True
ab6ea17fa84fe2ab054528617f42b5c36ce43883,PMC,"New Hepatitis E Virus Genotype in Bactrian Camels, Xinjiang, China, 2013",http://dx.doi.org/10.3201/eid2212.160979,PMC5189163,27869607,NO-CC CODE,,2016 Dec,"['Woo, Patrick C.Y.', 'Lau, Susanna K.P.', 'Teng, Jade L.L.', 'Cao, Kai-Yuan', 'Wernery, Ulrich', 'Schountz, Tony', 'Chiu, Tsz Ho', 'Tsang, Alan K.L.', 'Wong, Po-Chun', 'Wong, Emily Y.M.', 'Yuen, Kwok-Yung']",Emerg Infect Dis,,,False
523a530f03f2cd064a2d2c7cb6b3cb160926a803,PMC,Virus Variation Resource – improved response to emergent viral outbreaks,http://dx.doi.org/10.1093/nar/gkw1065,PMC5210549,27899678,NO-CC CODE,"The Virus Variation Resource is a value-added viral sequence data resource hosted by the National Center for Biotechnology Information. The resource is located at http://www.ncbi.nlm.nih.gov/genome/viruses/variation/ and includes modules for seven viral groups: influenza virus, Dengue virus, West Nile virus, Ebolavirus, MERS coronavirus, Rotavirus A and Zika virus. Each module is supported by pipelines that scan newly released GenBank records, annotate genes and proteins and parse sample descriptors and then map them to controlled vocabulary. These processes in turn support a purpose-built search interface where users can select sequences based on standardized gene, protein and metadata terms. Once sequences are selected, a suite of tools for downloading data, multi-sequence alignment and tree building supports a variety of user directed activities. This manuscript describes a series of features and functionalities recently added to the Virus Variation Resource.",2017 Jan 4,"['Hatcher, Eneida L.', 'Zhdanov, Sergey A.', 'Bao, Yiming', 'Blinkova, Olga', 'Nawrocki, Eric P.', 'Ostapchuck, Yuri', 'Schäffer, Alejandro A.', 'Brister, J. Rodney']",Nucleic Acids Res,,,True
652c4ca6d601033177d0dd2d9e0831950963b6f8,PMC,Multiple functions of USP18,http://dx.doi.org/10.1038/cddis.2016.326,PMC5260889,27809302,NO-CC CODE,"Since the discovery of the ubiquitin system and the description of its important role in the degradation of proteins, many studies have shown the importance of ubiquitin-specific peptidases (USPs). One special member of this family is the USP18 protein (formerly UBP43). In the past two decades, several functions of USP18 have been discovered: this protein is not only an isopeptidase but also a potent inhibitor of interferon signaling. Therefore, USP18 functions as 'a' maestro of many biological pathways in various cell types. This review outlines multiple functions of USP18 in the regulation of various immunological processes, including pathogen control, cancer development, and autoimmune diseases.",2016 Nov 3,"['Honke, Nadine', 'Shaabani, Namir', 'Zhang, Dong-Er', 'Hardt, Cornelia', 'Lang, Karl S']",Cell Death Dis,,,True
ef58b4dc1fbd69df709cfb1bd5e80a1ba03bc97b,PMC,"Evidence of human coroanvirus (229E), in patients with respiratory infection, Iran, 2015: the first report",,PMC5277600,28149491,NO-CC CODE,"BACKGROUND AND OBJECTIVES: Human coronaviruses (HCoVs) are one of the main causes of upper respiratory tract infections in humans. While more often responsible for mild illness, they have been associated with illnesses that require hospitalization. MATERIALS AND METHODS: 270 Samples from patients hospitalized with the respiratory infection during the autumn season of 2015 were evaluated for the presence of four HCoVs (OC43, 229E, HUK1, and NL63) using an optimized SYBR green RT-PCR assay. RESULTS: Fifteen HCoV-229E positive samples were identified (5.5 % positive). 85% of positive samples were male with the range of age between 12- 75 years old. CONCLUSION: It is the first comprehensive study on determination of the role of human coronaviruses in respiratory infections in Iran. Our data provide a novel insight into the epidemiology of HCoVs in Iran. Further studies are needed and should include the isolation and molecular characterization of HCoVs in Iran.",2016 Oct,"['Madhi, Ali', 'Ghalyanchilangeroudi, Arash', 'Soleimani, Mohammad']",Iran J Microbiol,,,True
5a7af4bc5cc14fbcd0bcc8d26515478c65a24406,PMC,Effectiveness of Antibiotic Use Management in Tianjin (2011–2013): A Quasi-Experimental Study,http://dx.doi.org/10.12659/MSM.899848,PMC5317282,28179620,NO-CC CODE,"BACKGROUND: In this study we investigated changes in the status of antibiotic use in Tianjin since the implementation of the Antibiotic Stewardship Program (ASP) (2011–2013), as well as existing problems, strategies, and outcomes to promote rational clinical antibiotic use. MATERIAL/METHODS: A quasi-experimental study was performed to investigate situations of antibiotic use in secondary and tertiary general hospitals in Tianjin from April 2011 to 2013. Five major indicators were analyzed: percentage of antibiotic use in inpatient cases (%), antibacterial use density (AUD), proportion of prophylactic antibiotic application for type I surgical incision, compliance rate of medication administration 0.5–2.0 h before such procedures, and antibiotic prophylaxis for ≤24 h in patients receiving these surgeries. RESULTS: There was a decrease in the percentage of antibiotic use across general hospitals (60.38% to 46.88%), in AUD (51.60% to 35.37%), and in the proportion of prophylactic antibiotic applications for type I incisions (86.67% to 25.08%). For patients undergoing these procedures, there was an increased compliance rate of medication administration of 0.5–2.0 h prior to surgery (86.38% to 100%), and of antibiotic prophylactic use for ≤24 h (40.30% to 96.37%). CONCLUSIONS: Implementation of the ASP campaign has reduced irrational antibiotic use, promoted rational antibiotic use, and delayed antibiotic resistance.",2017 Feb 9,"['Zhang, Hai-Hong', 'Du, Yue', 'Liu, Wei', 'Song, Shi-Duo', 'Zhao, Wen', 'Huang, Guo-Wei', 'Wang, He-Sheng']",Med Sci Monit,,,True
9a473a8b0c6f5a6d34a3201ab9635c5973149fd5,PMC,Highly Pathogenic Influenza A(H5Nx) Viruses with Altered H5 Receptor-Binding Specificity,http://dx.doi.org/10.3201/eid2302.161072,PMC5324792,27869615,NO-CC CODE,"Emergence and intercontinental spread of highly pathogenic avian influenza A(H5Nx) virus clade 2.3.4.4 is unprecedented. H5N8 and H5N2 viruses have caused major economic losses in the poultry industry in Europe and North America, and lethal human infections with H5N6 virus have occurred in Asia. Knowledge of the evolution of receptor-binding specificity of these viruses, which might affect host range, is urgently needed. We report that emergence of these viruses is accompanied by a change in receptor-binding specificity. In contrast to ancestral clade 2.3.4 H5 proteins, novel clade 2.3.4.4 H5 proteins bind to fucosylated sialosides because of substitutions K222Q and S227R, which are unique for highly pathogenic influenza virus H5 proteins. North American clade 2.3.4.4 virus isolates have retained only the K222Q substitution but still bind fucosylated sialosides. Altered receptor-binding specificity of virus clade 2.3.4.4 H5 proteins might have contributed to emergence and spread of H5Nx viruses.",2017 Feb,"['Guo, Hongbo', 'de Vries, Erik', 'McBride, Ryan', 'Dekkers, Jojanneke', 'Peng, Wenjie', 'Bouwman, Kim M.', 'Nycholat, Corwin', 'Verheije, M. Helene', 'Paulson, James C.', 'van Kuppeveld, Frank J.M.', 'de Haan, Cornelis A.M.']",Emerg Infect Dis,,,True
85c9d95797b7bf90bdc23ae36a2f43752128afcb,PMC,Highly Pathogenic Influenza A(H5Nx) Viruses with Altered H5 Receptor-Binding Specificity,http://dx.doi.org/10.3201/eid2302.161072,PMC5324792,27869615,NO-CC CODE,"Emergence and intercontinental spread of highly pathogenic avian influenza A(H5Nx) virus clade 2.3.4.4 is unprecedented. H5N8 and H5N2 viruses have caused major economic losses in the poultry industry in Europe and North America, and lethal human infections with H5N6 virus have occurred in Asia. Knowledge of the evolution of receptor-binding specificity of these viruses, which might affect host range, is urgently needed. We report that emergence of these viruses is accompanied by a change in receptor-binding specificity. In contrast to ancestral clade 2.3.4 H5 proteins, novel clade 2.3.4.4 H5 proteins bind to fucosylated sialosides because of substitutions K222Q and S227R, which are unique for highly pathogenic influenza virus H5 proteins. North American clade 2.3.4.4 virus isolates have retained only the K222Q substitution but still bind fucosylated sialosides. Altered receptor-binding specificity of virus clade 2.3.4.4 H5 proteins might have contributed to emergence and spread of H5Nx viruses.",2017 Feb,"['Guo, Hongbo', 'de Vries, Erik', 'McBride, Ryan', 'Dekkers, Jojanneke', 'Peng, Wenjie', 'Bouwman, Kim M.', 'Nycholat, Corwin', 'Verheije, M. Helene', 'Paulson, James C.', 'van Kuppeveld, Frank J.M.', 'de Haan, Cornelis A.M.']",Emerg Infect Dis,,,False
34d0858071fada0568643bf829c7349f56b28515,PMC,Livestock Susceptibility to Infection with Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.3201/eid2302.161239,PMC5324816,27901465,NO-CC CODE,"Middle East respiratory syndrome (MERS) cases continue to be reported, predominantly in Saudi Arabia and occasionally other countries. Although dromedaries are the main reservoir, other animal species might be susceptible to MERS coronavirus (MERS-CoV) infection and potentially serve as reservoirs. To determine whether other animals are potential reservoirs, we inoculated MERS-CoV into llamas, pigs, sheep, and horses and collected nasal and rectal swab samples at various times. The presence of MERS-CoV in the nose of pigs and llamas was confirmed by PCR, titration of infectious virus, immunohistochemistry, and in situ hybridization; seroconversion was detected in animals of both species. Conversely, in sheep and horses, virus-specific antibodies did not develop and no evidence of viral replication in the upper respiratory tract was found. These results prove the susceptibility of llamas and pigs to MERS-CoV infection. Thus, the possibility of MERS-CoV circulation in animals other than dromedaries, such as llamas and pigs, is not negligible.",2017 Feb,"['Vergara-Alert, Júlia', 'van den Brand, Judith M.A.', 'Widagdo, W.', 'Muñoz, Marta', 'Raj, Stalin', 'Schipper, Debby', 'Solanes, David', 'Cordón, Ivan', 'Bensaid, Albert', 'Haagmans, Bart L.', 'Segalés, Joaquim']",Emerg Infect Dis,,,True
fb488be48ad067eec86e76512e7e242becfc850d,PMC,Livestock Susceptibility to Infection with Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.3201/eid2302.161239,PMC5324816,27901465,NO-CC CODE,"Middle East respiratory syndrome (MERS) cases continue to be reported, predominantly in Saudi Arabia and occasionally other countries. Although dromedaries are the main reservoir, other animal species might be susceptible to MERS coronavirus (MERS-CoV) infection and potentially serve as reservoirs. To determine whether other animals are potential reservoirs, we inoculated MERS-CoV into llamas, pigs, sheep, and horses and collected nasal and rectal swab samples at various times. The presence of MERS-CoV in the nose of pigs and llamas was confirmed by PCR, titration of infectious virus, immunohistochemistry, and in situ hybridization; seroconversion was detected in animals of both species. Conversely, in sheep and horses, virus-specific antibodies did not develop and no evidence of viral replication in the upper respiratory tract was found. These results prove the susceptibility of llamas and pigs to MERS-CoV infection. Thus, the possibility of MERS-CoV circulation in animals other than dromedaries, such as llamas and pigs, is not negligible.",2017 Feb,"['Vergara-Alert, Júlia', 'van den Brand, Judith M.A.', 'Widagdo, W.', 'Muñoz, Marta', 'Raj, Stalin', 'Schipper, Debby', 'Solanes, David', 'Cordón, Ivan', 'Bensaid, Albert', 'Haagmans, Bart L.', 'Segalés, Joaquim']",Emerg Infect Dis,,,False
73c2273b28118421239c1275af22d309f1a44e4b,PMC,Loop Mediated Isothermal Amplification (LAMP) for Embryo Sex Determination in Pregnant Women at Eight Weeks of Pregnancy,,PMC5359858,28377900,NO-CC CODE,"BACKGROUND: In human, SRY (sex-determining region of the Y chromosome) is the major gene for the testis-determining factor which is found in normal XY males and in the rare XX males, and it is absent in normal XX females and many XY females. There are several methods which can indicate a male genotype by the presence of the amplified product of SRY gene. The aim of this study was to identify the SRY gene for embryo sex determination in human during pregnancy using loop mediated isothermal amplification (LAMP) method. METHODS: A total of 15 blood samples from pregnant women at eight weeks of pregnancy were collected, and Plasma DNA was extracted. LAMP assay was performed using DNA obtained for detection of SRY gene. Furthermore, colorimetric LAMP assay for rapid and easy detection of SRY gene was developed. RESULTS: LAMP results revealed that the positive reaction was highly specific only with samples containing XY chromosomes, while no amplification was found in samples containing XX chromosomes. A total of 15 blood samples from pregnant women were seven male embryos (46.6%) and eight female embryos (53.4%). All used visual components in the colorimetric assay could successfully make a clear distinction between positive and negative ones. CONCLUSION: The LAMP assay developed in this study is a valuable tool capable of monitoring the purity and detection of SRY gene for sex determination.",2017 Jan-Mar,"['Almasi, Mohammad Amin', 'Almasi, Galavizh']",J Reprod Infertil,,,True
9a68a4619502c6039c7b67be77cf1e73507ede65,PMC,"Surveillance and Testing for Middle East Respiratory Syndrome Coronavirus, Saudi Arabia, April 2015–February 2016",http://dx.doi.org/10.3201/eid2304.161793,PMC5367404,28322710,NO-CC CODE,"Saudi Arabia has reported >80% of the Middle East respiratory syndrome coronavirus (MERS-CoV) cases worldwide. During April 2015–February 2016, Saudi Arabia identified and tested 57,363 persons (18.4/10,000 residents) with suspected MERS-CoV infection; 384 (0.7%) tested positive. Robust, extensive, and timely surveillance is critical for limiting virus transmission.",2017 Apr,"['Bin Saeed, Abdulaziz A.', 'Abedi, Glen R.', 'Alzahrani, Abdullah G.', 'Salameh, Iyad', 'Abdirizak, Fatima', 'Alhakeem, Raafat', 'Algarni, Homoud', 'El Nil, Osman A.', 'Mohammed, Mutaz', 'Assiri, Abdullah M.', 'Alabdely, Hail M.', 'Watson, John T.', 'Gerber, Susan I.']",Emerg Infect Dis,,,True
777e2d21716c7c30bc37d19578f3ddfa61e0e11c,PMC,"Surveillance and Testing for Middle East Respiratory Syndrome Coronavirus, Saudi Arabia, April 2015–February 2016",http://dx.doi.org/10.3201/eid2304.161793,PMC5367404,28322710,NO-CC CODE,"Saudi Arabia has reported >80% of the Middle East respiratory syndrome coronavirus (MERS-CoV) cases worldwide. During April 2015–February 2016, Saudi Arabia identified and tested 57,363 persons (18.4/10,000 residents) with suspected MERS-CoV infection; 384 (0.7%) tested positive. Robust, extensive, and timely surveillance is critical for limiting virus transmission.",2017 Apr,"['Bin Saeed, Abdulaziz A.', 'Abedi, Glen R.', 'Alzahrani, Abdullah G.', 'Salameh, Iyad', 'Abdirizak, Fatima', 'Alhakeem, Raafat', 'Algarni, Homoud', 'El Nil, Osman A.', 'Mohammed, Mutaz', 'Assiri, Abdullah M.', 'Alabdely, Hail M.', 'Watson, John T.', 'Gerber, Susan I.']",Emerg Infect Dis,,,False
4bb2d045461c493bba023e72c87611ed59cf9f78,PMC,The Exploding Aliveness of the World,http://dx.doi.org/10.3201/eid2304.AC2304,PMC5367435,,NO-CC CODE,,2017 Apr,"['Breedlove, Byron', 'Arguin, Paul M.']",Emerg Infect Dis,,,True
768fb5bff1898a4076849b7d5318402a62cb0bfe,PMC,"Serologic Evidence for MERS-CoV Infection in Dromedary Camels, Punjab, Pakistan, 2012–2015",http://dx.doi.org/10.3201/eid2303.161285,PMC5382745,28221127,NO-CC CODE,"Dromedary camels from Africa and Arabia are an established source for zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) infection among humans. In Pakistan, we found specific neutralizing antibodies in samples from 39.5% of 565 dromedaries, documenting significant expansion of the enzootic range of MERS-CoV to Asia.",2017 Mar,"['Saqib, Muhammad', 'Sieberg, Andrea', 'Hussain, Muhammad Hammad', 'Mansoor, Muhammad Khalid', 'Zohaib, Ali', 'Lattwein, Erik', 'Müller, Marcel Alexander', 'Drosten, Christian', 'Corman, Victor Max']",Emerg Infect Dis,,,True
3ce427cdc17933b5d2a4834fe316196eec3c7113,PMC,"Serologic Evidence for MERS-CoV Infection in Dromedary Camels, Punjab, Pakistan, 2012–2015",http://dx.doi.org/10.3201/eid2303.161285,PMC5382745,28221127,NO-CC CODE,"Dromedary camels from Africa and Arabia are an established source for zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) infection among humans. In Pakistan, we found specific neutralizing antibodies in samples from 39.5% of 565 dromedaries, documenting significant expansion of the enzootic range of MERS-CoV to Asia.",2017 Mar,"['Saqib, Muhammad', 'Sieberg, Andrea', 'Hussain, Muhammad Hammad', 'Mansoor, Muhammad Khalid', 'Zohaib, Ali', 'Lattwein, Erik', 'Müller, Marcel Alexander', 'Drosten, Christian', 'Corman, Victor Max']",Emerg Infect Dis,,,False
18acb42cf96716cbb91dd26e491e253cc130cb78,PMC,Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor,http://dx.doi.org/10.1038/nature12711,PMC5389864,24172901,NO-CC CODE,"The 2002–3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history(1). An ongoing outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV)(2) suggests that this group of viruses remains a major threat and that their distribution is wider than previously recognized. Although bats have been suggested as the natural reservoirs of both viruses(3–5), attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa(5–8), but none are considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins (S) to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2)(9,10). Here, we report whole genome sequences of two novel bat CoVs from Chinese horseshoe bats (Family: Rhinolophidae) in Yunnan, China; RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat CoVs, particularly in the receptor binding domain (RDB) of the S protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat fecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses the ACE2s from human, civet and Chinese horseshoe bat for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.",2013 Nov 28,"['Ge, Xing-Yi', 'Li, Jia-Lu', 'Yang, Xing-Lou', 'Chmura, Aleksei A.', 'Zhu, Guangjian', 'Epstein, Jonathan H.', 'Mazet, Jonna K.', 'Hu, Ben', 'Zhang, Wei', 'Peng, Cheng', 'Zhang, Yu-Ji', 'Luo, Chu-Ming', 'Tan, Bing', 'Wang, Ning', 'Zhu, Yan', 'Crameri, Gary', 'Zhang, Shu-Yi', 'Wang, Lin-Fa', 'Daszak, Peter', 'Shi, Zheng-Li']",Nature,,,True
17ad982bf94d44ae2cc3e26362ec70d70cbc6c31,PMC,"Population Responses during the Pandemic Phase of the Influenza A(H1N1)pdm09 Epidemic, Hong Kong, China",http://dx.doi.org/10.3201/eid2305.160768,PMC5403031,28418300,NO-CC CODE,"During August 2009–July 2010, we conducted 7 longitudinal telephone surveys among 503 adults in Hong Kong, China, to explore changes in their behavioral and psychological responses to the influenza A(H1N1)pdm09 virus epidemic. Trends were examined using generalized estimating equations models. Findings showed that responses varied with the course of the pandemic.",2017 May,"['Yeung, Nelson C.Y.', 'Lau, Joseph T.F.', 'Choi, Kai Chow', 'Griffiths, Sian']",Emerg Infect Dis,,,True
b6b194382723f8c929c36eb1e7e80394f0a105fd,PMC,"Population Responses during the Pandemic Phase of the Influenza A(H1N1)pdm09 Epidemic, Hong Kong, China",http://dx.doi.org/10.3201/eid2305.160768,PMC5403031,28418300,NO-CC CODE,"During August 2009–July 2010, we conducted 7 longitudinal telephone surveys among 503 adults in Hong Kong, China, to explore changes in their behavioral and psychological responses to the influenza A(H1N1)pdm09 virus epidemic. Trends were examined using generalized estimating equations models. Findings showed that responses varied with the course of the pandemic.",2017 May,"['Yeung, Nelson C.Y.', 'Lau, Joseph T.F.', 'Choi, Kai Chow', 'Griffiths, Sian']",Emerg Infect Dis,,,True
4438de01e4b0376bfa446b4234e599fb234cb6b1,PMC,Structural basis for the specificity of USP18 towards ISG15,http://dx.doi.org/10.1038/nsmb.3371,PMC5405867,28165509,NO-CC CODE,"Protein modification by ubiquitin and ubiquitin-like modifiers (Ubls) is counteracted by ubiquitin- and Ubl-proteases collectively called DUBs. In contrast to other proteases of the ubiquitin-specific protease (USP) family, USP18 shows no reactivity towards ubiquitin but specifically deconjugates the interferon induced Ubl ISG15. To identify molecular determinants for this specificity, we solved the crystal structures of mouse USP18 and of mouse USP18 in complex with mouse ISG15. USP18 was crystallized in an open and a closed conformation revealing high flexibility of the enzyme. Structural data, biochemical and mutational analysis showed that only the C-terminal ubiquitin-like domain of ISG15 is recognized and essential for USP18 activity. A critical hydrophobic patch in USP18 interacts with a hydrophobic region unique to ISG15 providing evidence that ISG15 specificity of USP18 is mediated by a small interaction interface. Our results may provide the structural basis for the development of new drugs modulating ISGylation.",2017 Mar 6,"['Basters, Anja', 'Geurink, Paul P.', 'Röcker, Annika', 'Witting, Katharina F.', 'Tadayon, Roya', 'Hess, Sandra', 'Semrau, Marta S.', 'Storici, Paola', 'Ovaa, Huib', 'Knobeloch, Klaus-Peter', 'Fritz, Günter']",Nat Struct Mol Biol,,,True
7c47ab5430b5f3c97399faf245e08c30b4c38de3,PMC,Structural basis for the specificity of USP18 towards ISG15,http://dx.doi.org/10.1038/nsmb.3371,PMC5405867,28165509,NO-CC CODE,"Protein modification by ubiquitin and ubiquitin-like modifiers (Ubls) is counteracted by ubiquitin- and Ubl-proteases collectively called DUBs. In contrast to other proteases of the ubiquitin-specific protease (USP) family, USP18 shows no reactivity towards ubiquitin but specifically deconjugates the interferon induced Ubl ISG15. To identify molecular determinants for this specificity, we solved the crystal structures of mouse USP18 and of mouse USP18 in complex with mouse ISG15. USP18 was crystallized in an open and a closed conformation revealing high flexibility of the enzyme. Structural data, biochemical and mutational analysis showed that only the C-terminal ubiquitin-like domain of ISG15 is recognized and essential for USP18 activity. A critical hydrophobic patch in USP18 interacts with a hydrophobic region unique to ISG15 providing evidence that ISG15 specificity of USP18 is mediated by a small interaction interface. Our results may provide the structural basis for the development of new drugs modulating ISGylation.",2017 Mar 6,"['Basters, Anja', 'Geurink, Paul P.', 'Röcker, Annika', 'Witting, Katharina F.', 'Tadayon, Roya', 'Hess, Sandra', 'Semrau, Marta S.', 'Storici, Paola', 'Ovaa, Huib', 'Knobeloch, Klaus-Peter', 'Fritz, Günter']",Nat Struct Mol Biol,,,False
ed5b533b4656e7cef769c43e7e59d862fd9cfe1a,PMC,Structural basis for the specificity of USP18 towards ISG15,http://dx.doi.org/10.1038/nsmb.3371,PMC5405867,28165509,NO-CC CODE,"Protein modification by ubiquitin and ubiquitin-like modifiers (Ubls) is counteracted by ubiquitin- and Ubl-proteases collectively called DUBs. In contrast to other proteases of the ubiquitin-specific protease (USP) family, USP18 shows no reactivity towards ubiquitin but specifically deconjugates the interferon induced Ubl ISG15. To identify molecular determinants for this specificity, we solved the crystal structures of mouse USP18 and of mouse USP18 in complex with mouse ISG15. USP18 was crystallized in an open and a closed conformation revealing high flexibility of the enzyme. Structural data, biochemical and mutational analysis showed that only the C-terminal ubiquitin-like domain of ISG15 is recognized and essential for USP18 activity. A critical hydrophobic patch in USP18 interacts with a hydrophobic region unique to ISG15 providing evidence that ISG15 specificity of USP18 is mediated by a small interaction interface. Our results may provide the structural basis for the development of new drugs modulating ISGylation.",2017 Mar 6,"['Basters, Anja', 'Geurink, Paul P.', 'Röcker, Annika', 'Witting, Katharina F.', 'Tadayon, Roya', 'Hess, Sandra', 'Semrau, Marta S.', 'Storici, Paola', 'Ovaa, Huib', 'Knobeloch, Klaus-Peter', 'Fritz, Günter']",Nat Struct Mol Biol,,,False
d0e1735b8e1aa2448475c0e317ad01cac96f0701,PMC,Pulmonary Histoplasma Infection After Allogeneic Hematopoietic Stem Cell Transplantation: Case Report and Review of the Literature,http://dx.doi.org/10.1093/ofid/ofx041,PMC5407209,28470019,NO-CC CODE,"Histoplasmosis causes a wide spectrum of clinical illness, including disseminated infection in the immunocompromised. We report a case of pulmonary histoplasmosis in an allogeneic stem cell transplant recipient and review the literature on this topic. Histoplasmosis in this patient population is uncommon, but it is associated with poor outcome.",2017 Mar 1,"['Natarajan, Mukil', 'Swierzbinski, Matthew J.', 'Maxwell, Sandra', 'Zelazny, Adrian M.', 'Fahle, Gary A.', 'Quezado, Martha', 'Barrett, John', 'Battiwalla, Minoo', 'Lionakis, Michail S.']",Open Forum Infect Dis,,,True
992c7e3cd0a143b2506bcbe51d1cda024fb5b526,PMC,INHIBITORY EFFECT OF EMODIN ON RAW 264.7 ACTIVATED WITH DOUBLE STRANDED RNA ANALOGUE POLY I:C,http://dx.doi.org/10.21010/ajtcam.v14i3.17,PMC5412221,28480427,NO-CC CODE,"BACKGROUND: Emodin (3-methyl-1, 6, 8-trihydroxyanthraquinone) is a compound which can be found in Polygoni Multiflori Radix (PMR). PMR is the root of Polygonum multiflorum. PMR is used to treat dizziness, spermatorrhea, sores, and scrofula as well as chronic malaria traditionally in China and Korea. The anti-tumor property of emodin was already reported. However, anti-viral activity of emodin on macrophages are not fully reported. MATERIALS AND METHODS: Effects of emodin on RAW 264.7 mouse macrophages induced by polyinosinic-polycytidylic acid (poly I:C), a synthetic analog of double-stranded RNA, were evaluated. RESULTS: Emodin restored the cell viability in poly I: C-induced RAW 264.7 at concentrations of up to 50 μM. Emodin significantly inhibited the production of nitric oxide, IL-1α, IL-Ιβ, IL-6, GM-CSF, G-CSF, M-CSF, MCP-1, MIP-1a, MIP-Ιβ, MIP-2, RANTES, and IP-10 as well as calcium release and mRNA expression of signal transducer and activated transcription 1 (STAT1) in poly I:C-induced RAW 264.7 (P < 0.05). CONCLUSION: This study shows the inhibitory effect of emodin on poly I: C-induced RAW 264.7 via calcium-STAT pathway.",2017 Mar 1,"['Kim, Young-Jin', 'Lee, Ji Young', 'Kim, Hyun-Ju', 'Kim, Do-Hoon', 'Lee, Tae Hee', 'Kang, Mi Suk', 'Choi, You-Kyung', 'Lee, Hye Lim', 'Kim, Jaieun', 'An, Hyo-Jin', 'Park, Wansu']",Afr J Tradit Complement Altern Med,,,True
183dc10a5eac02c39b5c2b6151c6eb6fc6cf88a3,PMC,"Hospital Outbreaks of Middle East Respiratory Syndrome, Daejeon, South Korea, 2015",http://dx.doi.org/10.3201/eid2306.160120,PMC5443424,28516865,NO-CC CODE,"From May through July 2015, a total of 26 cases of Middle East Respiratory Syndrome were reported from 2 hospitals in Daejeon, South Korea, including 1 index case and 25 new cases. We examined the epidemiologic features of these cases and found an estimated median incubation period of 6.1 days (8.8 days in hospital A and 4.6 days in hospital B). The overall attack rate was 3.7% (4.7% in hospital A and 3.0% in hospital B), and the attack rates among inpatients and caregivers in the same ward were 12.3% and 22.5%, respectively. The overall case-fatality rate was 44.0% (28.6% in hospital A and 63.6% in hospital B). The use of cohort quarantine may have played a role in preventing community spread, but additional transmission occurred among members of the hospital cohort quarantined together. Caregivers may have contributed in part to the transmission.",2017 Jun,"['Park, Jung Wan', 'Lee, Keon Joo', 'Lee, Kang Hyoung', 'Lee, Sang Hyup', 'Cho, Jung Rae', 'Mo, Jin Won', 'Choi, Soo Young', 'Kwon, Geun Yong', 'Shin, Ji-Yeon', 'Hong, Jee Young', 'Kim, Jin', 'Yeon, Mi-Yeon', 'Oh, Jong Seok', 'Nam, Hae-Sung']",Emerg Infect Dis,,,True
3c9ff87937f85538b113a6ec97405c518c1c880b,PMC,"Hospital Outbreaks of Middle East Respiratory Syndrome, Daejeon, South Korea, 2015",http://dx.doi.org/10.3201/eid2306.160120,PMC5443424,28516865,NO-CC CODE,"From May through July 2015, a total of 26 cases of Middle East Respiratory Syndrome were reported from 2 hospitals in Daejeon, South Korea, including 1 index case and 25 new cases. We examined the epidemiologic features of these cases and found an estimated median incubation period of 6.1 days (8.8 days in hospital A and 4.6 days in hospital B). The overall attack rate was 3.7% (4.7% in hospital A and 3.0% in hospital B), and the attack rates among inpatients and caregivers in the same ward were 12.3% and 22.5%, respectively. The overall case-fatality rate was 44.0% (28.6% in hospital A and 63.6% in hospital B). The use of cohort quarantine may have played a role in preventing community spread, but additional transmission occurred among members of the hospital cohort quarantined together. Caregivers may have contributed in part to the transmission.",2017 Jun,"['Park, Jung Wan', 'Lee, Keon Joo', 'Lee, Kang Hyoung', 'Lee, Sang Hyup', 'Cho, Jung Rae', 'Mo, Jin Won', 'Choi, Soo Young', 'Kwon, Geun Yong', 'Shin, Ji-Yeon', 'Hong, Jee Young', 'Kim, Jin', 'Yeon, Mi-Yeon', 'Oh, Jong Seok', 'Nam, Hae-Sung']",Emerg Infect Dis,,,False
f2d1c4e958f633fefcb90c78a29c8c19bb0562ad,PMC,Sustainability of High-Level Isolation Capabilities among US Ebola Treatment Centers,http://dx.doi.org/10.3201/eid2306.170062,PMC5443454,28518036,NO-CC CODE,"To identify barriers to maintaining and applying capabilities of US high-level isolation units (HLIUs) used during the Ebola virus disease outbreak, during 2016 we surveyed HLIUs. HLIUs identified sustainability challenges and reported the highly infectious diseases they would treat. HLIUs expended substantial resources in development but must strategize models of sustainability to maintain readiness.",2017 Jun,"['Herstein, Jocelyn J.', 'Biddinger, Paul D.', 'Gibbs, Shawn G.', 'Le, Aurora B.', 'Jelden, Katelyn C.', 'Hewlett, Angela L.', 'Lowe, John J.']",Emerg Infect Dis,,,True
29646e3d897ae1232a6a1577635d75bc9ae94bc6,PMC,Domestic Pig Unlikely Reservoir for MERS-CoV,http://dx.doi.org/10.3201/eid2306.170096,PMC5443456,28318484,NO-CC CODE,"We tested the suitability of the domestic pig as a model for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Inoculation did not cause disease, but a low level of virus replication, shedding, and seroconversion were observed. Pigs do not recapitulate human MERS-CoV and are unlikely to constitute a reservoir in nature.",2017 Jun,"['de Wit, Emmie', 'Feldmann, Friederike', 'Horne, Eva', 'Martellaro, Cynthia', 'Haddock, Elaine', 'Bushmaker, Trenton', 'Rosenke, Kyle', 'Okumura, Atsushi', 'Rosenke, Rebecca', 'Saturday, Greg', 'Scott, Dana', 'Feldmann, Heinz']",Emerg Infect Dis,,,True
76d2a690120b972075f49370c5b27aaa61763df2,PMC,Law as a Tool for Preventing Chronic Diseases: Expanding the Spectrum of Effective Public Health Strategies,,PMC544536,15634375,NO-CC CODE,"Law, which is a fundamental element of effective public health policy and practice, played a crucial role in many of public health's greatest achievements of the 20th century. Still, conceptual legal frameworks for the systematic application of law to chronic disease prevention and control have not been fully recognized and used to address public health needs. Development and implementation of legal frameworks could broaden the range of effective public health strategies and provide valuable tools for the public health workforce, especially for state and local health department program managers and state and national policy makers. In an effort to expand the range of effective public health interventions, the Centers for Disease Control and Prevention will work with its partners to explore the development of systematic legal frameworks as a tool for preventing chronic diseases and addressing the growing epidemic of obesity, heart disease, stroke, and other chronic diseases and their risk factors.",2003 Dec 15,"['Mensah, George A.', 'Goodman, Richard A.', 'Zaza, Stephanie', 'Moulton, Anthony D.', 'Kocher, Paula L.', 'Dietz, William H.', 'Pechacek, Terry F.', 'Marks, James S.']",Prev Chronic Dis,,,True
cb70928ef1e8112feb2a802c88996237f95a524e,PMC,"Topology Engineering of Proteins in Vivo Using Genetically Encoded, Mechanically Interlocking SpyX Modules for Enhanced Stability",http://dx.doi.org/10.1021/acscentsci.7b00104,PMC5445526,28573210,NO-CC CODE,"[Image: see text] Recombinant proteins are traditionally limited to linear configuration. Herein, we report in vivo protein topology engineering using highly efficient, mechanically interlocking SpyX modules named AXB and BXA. SpyX modules are protein domains composed of p53dim (X), SpyTag (A), and SpyCatcher (B). The p53dim guides the intertwining of the two nascent protein chains followed by autocatalytic isopeptide bond formation between SpyTag and SpyCatcher to fulfill the interlocking, leading to a variety of backbone topologies. Direct expression of AXB or BXA produces protein catenanes with distinct ring sizes. Recombinant proteins containing SpyX modules are obtained either as mechanically interlocked obligate dimers if the protein of interest is fused to the N- or C-terminus of SpyX modules, or as star proteins if the protein is fused to both N- and C-termini. As examples, cellular syntheses of dimers of (GB1)(2) (where GB1 stands for immunoglobulin-binding domain B1 of streptococcal protein G) and of four-arm elastin-like star proteins were demonstrated. Comparison of the catenation efficiencies in different constructs reveals that BXA is generally much more effective than AXB, which is rationalized by the arrangement of three domains in space. Mechanical interlocking induces considerable stability enhancement. Both AXB and BXA have a melting point ∼20 °C higher than the linear controls and the BXA catenane has a melting point ~2 °C higher than the cyclic control BX’A. Notably, four-arm elastin-like star proteins demonstrate remarkable tolerance against trypsin digestion. The SpyX modules provide a convenient and versatile approach to construct unconventional protein topologies via the “assembly-reaction” synergy, which opens a new horizon in protein science for stability enhancement and function reinforcement via topology engineering.",2017 May 24,"['Liu, Dong', 'Wu, Wen-Hao', 'Liu, Ya-Jie', 'Wu, Xia-Ling', 'Cao, Yang', 'Song, Bo', 'Li, Xiaopeng', 'Zhang, Wen-Bin']",ACS Cent Sci,,,True
b7089fc75836770d44da4bc7d6200e81426b2d4e,PMC,"Topology Engineering of Proteins in Vivo Using Genetically Encoded, Mechanically Interlocking SpyX Modules for Enhanced Stability",http://dx.doi.org/10.1021/acscentsci.7b00104,PMC5445526,28573210,NO-CC CODE,"[Image: see text] Recombinant proteins are traditionally limited to linear configuration. Herein, we report in vivo protein topology engineering using highly efficient, mechanically interlocking SpyX modules named AXB and BXA. SpyX modules are protein domains composed of p53dim (X), SpyTag (A), and SpyCatcher (B). The p53dim guides the intertwining of the two nascent protein chains followed by autocatalytic isopeptide bond formation between SpyTag and SpyCatcher to fulfill the interlocking, leading to a variety of backbone topologies. Direct expression of AXB or BXA produces protein catenanes with distinct ring sizes. Recombinant proteins containing SpyX modules are obtained either as mechanically interlocked obligate dimers if the protein of interest is fused to the N- or C-terminus of SpyX modules, or as star proteins if the protein is fused to both N- and C-termini. As examples, cellular syntheses of dimers of (GB1)(2) (where GB1 stands for immunoglobulin-binding domain B1 of streptococcal protein G) and of four-arm elastin-like star proteins were demonstrated. Comparison of the catenation efficiencies in different constructs reveals that BXA is generally much more effective than AXB, which is rationalized by the arrangement of three domains in space. Mechanical interlocking induces considerable stability enhancement. Both AXB and BXA have a melting point ∼20 °C higher than the linear controls and the BXA catenane has a melting point ~2 °C higher than the cyclic control BX’A. Notably, four-arm elastin-like star proteins demonstrate remarkable tolerance against trypsin digestion. The SpyX modules provide a convenient and versatile approach to construct unconventional protein topologies via the “assembly-reaction” synergy, which opens a new horizon in protein science for stability enhancement and function reinforcement via topology engineering.",2017 May 24,"['Liu, Dong', 'Wu, Wen-Hao', 'Liu, Ya-Jie', 'Wu, Xia-Ling', 'Cao, Yang', 'Song, Bo', 'Li, Xiaopeng', 'Zhang, Wen-Bin']",ACS Cent Sci,,,True
09fc4c5e368a43d21f5130cb8474d61d65191dd9,PMC,Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality,http://dx.doi.org/10.1093/nar/gki193,PMC546170,15653644,NO-CC CODE,"Therapeutic application of the recently discovered small interfering RNA (siRNA) gene silencing phenomenon will be dependent on improvements in molecule bio-stability, specificity and delivery. To address these issues, we have systematically modified siRNA with the synthetic RNA-like high affinity nucleotide analogue, Locked Nucleic Acid (LNA). Here, we show that incorporation of LNA substantially enhances serum half-life of siRNA's, which is a key requirement for therapeutic use. Moreover, we provide evidence that LNA is compatible with the intracellular siRNA machinery and can be used to reduce undesired, sequence-related off-target effects. LNA-modified siRNAs targeting the emerging disease SARS, show improved efficiency over unmodified siRNA on certain RNA motifs. The results from this study emphasize LNA's promise in converting siRNA from a functional genomics technology to a therapeutic platform.",2005 Jan 14,"['Elmén, Joacim', 'Thonberg, Håkan', 'Ljungberg, Karl', 'Frieden, Miriam', 'Westergaard, Majken', 'Xu, Yunhe', 'Wahren, Britta', 'Liang, Zicai', 'Ørum, Henrik', 'Koch, Troels', 'Wahlestedt, Claes']",Nucleic Acids Res,,,True
f1d1b9694aa43c837d9b758cb2d45d8a24d293e3,PMC,Detection and characterization of horizontal transfers in prokaryotes using genomic signature,http://dx.doi.org/10.1093/nar/gni004,PMC546175,15653627,NO-CC CODE,"Horizontal DNA transfer is an important factor of evolution and participates in biological diversity. Unfortunately, the location and length of horizontal transfers (HTs) are known for very few species. The usage of short oligonucleotides in a sequence (the so-called genomic signature) has been shown to be species-specific even in DNA fragments as short as 1 kb. The genomic signature is therefore proposed as a tool to detect HTs. Since DNA transfers originate from species with a signature different from those of the recipient species, the analysis of local variations of signature along recipient genome may allow for detecting exogenous DNA. The strategy consists in (i) scanning the genome with a sliding window, and calculating the corresponding local signature (ii) evaluating its deviation from the signature of the whole genome and (iii) looking for similar signatures in a database of genomic signatures. A total of 22 prokaryote genomes are analyzed in this way. It has been observed that atypical regions make up ∼6% of each genome on the average. Most of the claimed HTs as well as new ones are detected. The origin of putative DNA transfers is looked for among ∼12 000 species. Donor species are proposed and sometimes strongly suggested, considering similarity of signatures. Among the species studied, Bacillus subtilis, Haemophilus Influenzae and Escherichia coli are investigated by many authors and give the opportunity to perform a thorough comparison of most of the bioinformatics methods used to detect HTs.",2005 Jan 13,"['Dufraigne, Christine', 'Fertil, Bernard', 'Lespinats, Sylvain', 'Giron, Alain', 'Deschavanne, Patrick']",Nucleic Acids Res,,,True
4819c0558a6034d3edd5147306063ddc899a1b21,PMC,Detection and characterization of horizontal transfers in prokaryotes using genomic signature,http://dx.doi.org/10.1093/nar/gni004,PMC546175,15653627,NO-CC CODE,"Horizontal DNA transfer is an important factor of evolution and participates in biological diversity. Unfortunately, the location and length of horizontal transfers (HTs) are known for very few species. The usage of short oligonucleotides in a sequence (the so-called genomic signature) has been shown to be species-specific even in DNA fragments as short as 1 kb. The genomic signature is therefore proposed as a tool to detect HTs. Since DNA transfers originate from species with a signature different from those of the recipient species, the analysis of local variations of signature along recipient genome may allow for detecting exogenous DNA. The strategy consists in (i) scanning the genome with a sliding window, and calculating the corresponding local signature (ii) evaluating its deviation from the signature of the whole genome and (iii) looking for similar signatures in a database of genomic signatures. A total of 22 prokaryote genomes are analyzed in this way. It has been observed that atypical regions make up ∼6% of each genome on the average. Most of the claimed HTs as well as new ones are detected. The origin of putative DNA transfers is looked for among ∼12 000 species. Donor species are proposed and sometimes strongly suggested, considering similarity of signatures. Among the species studied, Bacillus subtilis, Haemophilus Influenzae and Escherichia coli are investigated by many authors and give the opportunity to perform a thorough comparison of most of the bioinformatics methods used to detect HTs.",2005 Jan 13,"['Dufraigne, Christine', 'Fertil, Bernard', 'Lespinats, Sylvain', 'Giron, Alain', 'Deschavanne, Patrick']",Nucleic Acids Res,,,False
8ff393a301e0a033e3781bbb24726ca7037da349,PMC,Detection and characterization of horizontal transfers in prokaryotes using genomic signature,http://dx.doi.org/10.1093/nar/gni004,PMC546175,15653627,NO-CC CODE,"Horizontal DNA transfer is an important factor of evolution and participates in biological diversity. Unfortunately, the location and length of horizontal transfers (HTs) are known for very few species. The usage of short oligonucleotides in a sequence (the so-called genomic signature) has been shown to be species-specific even in DNA fragments as short as 1 kb. The genomic signature is therefore proposed as a tool to detect HTs. Since DNA transfers originate from species with a signature different from those of the recipient species, the analysis of local variations of signature along recipient genome may allow for detecting exogenous DNA. The strategy consists in (i) scanning the genome with a sliding window, and calculating the corresponding local signature (ii) evaluating its deviation from the signature of the whole genome and (iii) looking for similar signatures in a database of genomic signatures. A total of 22 prokaryote genomes are analyzed in this way. It has been observed that atypical regions make up ∼6% of each genome on the average. Most of the claimed HTs as well as new ones are detected. The origin of putative DNA transfers is looked for among ∼12 000 species. Donor species are proposed and sometimes strongly suggested, considering similarity of signatures. Among the species studied, Bacillus subtilis, Haemophilus Influenzae and Escherichia coli are investigated by many authors and give the opportunity to perform a thorough comparison of most of the bioinformatics methods used to detect HTs.",2005 Jan 13,"['Dufraigne, Christine', 'Fertil, Bernard', 'Lespinats, Sylvain', 'Giron, Alain', 'Deschavanne, Patrick']",Nucleic Acids Res,,,False
d7b699f75d71278245ec73e1fdae0b5fc61df2f2,PMC,Detection and characterization of horizontal transfers in prokaryotes using genomic signature,http://dx.doi.org/10.1093/nar/gni004,PMC546175,15653627,NO-CC CODE,"Horizontal DNA transfer is an important factor of evolution and participates in biological diversity. Unfortunately, the location and length of horizontal transfers (HTs) are known for very few species. The usage of short oligonucleotides in a sequence (the so-called genomic signature) has been shown to be species-specific even in DNA fragments as short as 1 kb. The genomic signature is therefore proposed as a tool to detect HTs. Since DNA transfers originate from species with a signature different from those of the recipient species, the analysis of local variations of signature along recipient genome may allow for detecting exogenous DNA. The strategy consists in (i) scanning the genome with a sliding window, and calculating the corresponding local signature (ii) evaluating its deviation from the signature of the whole genome and (iii) looking for similar signatures in a database of genomic signatures. A total of 22 prokaryote genomes are analyzed in this way. It has been observed that atypical regions make up ∼6% of each genome on the average. Most of the claimed HTs as well as new ones are detected. The origin of putative DNA transfers is looked for among ∼12 000 species. Donor species are proposed and sometimes strongly suggested, considering similarity of signatures. Among the species studied, Bacillus subtilis, Haemophilus Influenzae and Escherichia coli are investigated by many authors and give the opportunity to perform a thorough comparison of most of the bioinformatics methods used to detect HTs.",2005 Jan 13,"['Dufraigne, Christine', 'Fertil, Bernard', 'Lespinats, Sylvain', 'Giron, Alain', 'Deschavanne, Patrick']",Nucleic Acids Res,,,False
28dbd18b1b910e5763fbb23ba0a0b852643ab01e,PMC,Detection and characterization of horizontal transfers in prokaryotes using genomic signature,http://dx.doi.org/10.1093/nar/gni004,PMC546175,15653627,NO-CC CODE,"Horizontal DNA transfer is an important factor of evolution and participates in biological diversity. Unfortunately, the location and length of horizontal transfers (HTs) are known for very few species. The usage of short oligonucleotides in a sequence (the so-called genomic signature) has been shown to be species-specific even in DNA fragments as short as 1 kb. The genomic signature is therefore proposed as a tool to detect HTs. Since DNA transfers originate from species with a signature different from those of the recipient species, the analysis of local variations of signature along recipient genome may allow for detecting exogenous DNA. The strategy consists in (i) scanning the genome with a sliding window, and calculating the corresponding local signature (ii) evaluating its deviation from the signature of the whole genome and (iii) looking for similar signatures in a database of genomic signatures. A total of 22 prokaryote genomes are analyzed in this way. It has been observed that atypical regions make up ∼6% of each genome on the average. Most of the claimed HTs as well as new ones are detected. The origin of putative DNA transfers is looked for among ∼12 000 species. Donor species are proposed and sometimes strongly suggested, considering similarity of signatures. Among the species studied, Bacillus subtilis, Haemophilus Influenzae and Escherichia coli are investigated by many authors and give the opportunity to perform a thorough comparison of most of the bioinformatics methods used to detect HTs.",2005 Jan 13,"['Dufraigne, Christine', 'Fertil, Bernard', 'Lespinats, Sylvain', 'Giron, Alain', 'Deschavanne, Patrick']",Nucleic Acids Res,,,False
d5108b6c885b4234f31781e459203190209a5872,PMC,Detection and characterization of horizontal transfers in prokaryotes using genomic signature,http://dx.doi.org/10.1093/nar/gni004,PMC546175,15653627,NO-CC CODE,"Horizontal DNA transfer is an important factor of evolution and participates in biological diversity. Unfortunately, the location and length of horizontal transfers (HTs) are known for very few species. The usage of short oligonucleotides in a sequence (the so-called genomic signature) has been shown to be species-specific even in DNA fragments as short as 1 kb. The genomic signature is therefore proposed as a tool to detect HTs. Since DNA transfers originate from species with a signature different from those of the recipient species, the analysis of local variations of signature along recipient genome may allow for detecting exogenous DNA. The strategy consists in (i) scanning the genome with a sliding window, and calculating the corresponding local signature (ii) evaluating its deviation from the signature of the whole genome and (iii) looking for similar signatures in a database of genomic signatures. A total of 22 prokaryote genomes are analyzed in this way. It has been observed that atypical regions make up ∼6% of each genome on the average. Most of the claimed HTs as well as new ones are detected. The origin of putative DNA transfers is looked for among ∼12 000 species. Donor species are proposed and sometimes strongly suggested, considering similarity of signatures. Among the species studied, Bacillus subtilis, Haemophilus Influenzae and Escherichia coli are investigated by many authors and give the opportunity to perform a thorough comparison of most of the bioinformatics methods used to detect HTs.",2005 Jan 13,"['Dufraigne, Christine', 'Fertil, Bernard', 'Lespinats, Sylvain', 'Giron, Alain', 'Deschavanne, Patrick']",Nucleic Acids Res,,,False
fe1cb18dbcf6b77b8f161d0d9bd883f6db01b73e,PMC,Detection and characterization of horizontal transfers in prokaryotes using genomic signature,http://dx.doi.org/10.1093/nar/gni004,PMC546175,15653627,NO-CC CODE,"Horizontal DNA transfer is an important factor of evolution and participates in biological diversity. Unfortunately, the location and length of horizontal transfers (HTs) are known for very few species. The usage of short oligonucleotides in a sequence (the so-called genomic signature) has been shown to be species-specific even in DNA fragments as short as 1 kb. The genomic signature is therefore proposed as a tool to detect HTs. Since DNA transfers originate from species with a signature different from those of the recipient species, the analysis of local variations of signature along recipient genome may allow for detecting exogenous DNA. The strategy consists in (i) scanning the genome with a sliding window, and calculating the corresponding local signature (ii) evaluating its deviation from the signature of the whole genome and (iii) looking for similar signatures in a database of genomic signatures. A total of 22 prokaryote genomes are analyzed in this way. It has been observed that atypical regions make up ∼6% of each genome on the average. Most of the claimed HTs as well as new ones are detected. The origin of putative DNA transfers is looked for among ∼12 000 species. Donor species are proposed and sometimes strongly suggested, considering similarity of signatures. Among the species studied, Bacillus subtilis, Haemophilus Influenzae and Escherichia coli are investigated by many authors and give the opportunity to perform a thorough comparison of most of the bioinformatics methods used to detect HTs.",2005 Jan 13,"['Dufraigne, Christine', 'Fertil, Bernard', 'Lespinats, Sylvain', 'Giron, Alain', 'Deschavanne, Patrick']",Nucleic Acids Res,,,False
af1204bdffc3a96ed501d22472ecb9a3a466221e,PMC,Detection and characterization of horizontal transfers in prokaryotes using genomic signature,http://dx.doi.org/10.1093/nar/gni004,PMC546175,15653627,NO-CC CODE,"Horizontal DNA transfer is an important factor of evolution and participates in biological diversity. Unfortunately, the location and length of horizontal transfers (HTs) are known for very few species. The usage of short oligonucleotides in a sequence (the so-called genomic signature) has been shown to be species-specific even in DNA fragments as short as 1 kb. The genomic signature is therefore proposed as a tool to detect HTs. Since DNA transfers originate from species with a signature different from those of the recipient species, the analysis of local variations of signature along recipient genome may allow for detecting exogenous DNA. The strategy consists in (i) scanning the genome with a sliding window, and calculating the corresponding local signature (ii) evaluating its deviation from the signature of the whole genome and (iii) looking for similar signatures in a database of genomic signatures. A total of 22 prokaryote genomes are analyzed in this way. It has been observed that atypical regions make up ∼6% of each genome on the average. Most of the claimed HTs as well as new ones are detected. The origin of putative DNA transfers is looked for among ∼12 000 species. Donor species are proposed and sometimes strongly suggested, considering similarity of signatures. Among the species studied, Bacillus subtilis, Haemophilus Influenzae and Escherichia coli are investigated by many authors and give the opportunity to perform a thorough comparison of most of the bioinformatics methods used to detect HTs.",2005 Jan 13,"['Dufraigne, Christine', 'Fertil, Bernard', 'Lespinats, Sylvain', 'Giron, Alain', 'Deschavanne, Patrick']",Nucleic Acids Res,,,False
6e8f150cd587ddd87cd4220351db7f0b6cd1e006,PMC,Identification of a Peptide for Systemic Brain Delivery of a Morpholino Oligonucleotide in Mouse Models of Spinal Muscular Atrophy,http://dx.doi.org/10.1089/nat.2016.0652,PMC5467147,28118087,NO-CC CODE,"Splice-switching antisense oligonucleotides are emerging treatments for neuromuscular diseases, with several splice-switching oligonucleotides (SSOs) currently undergoing clinical trials such as for Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). However, the development of systemically delivered antisense therapeutics has been hampered by poor tissue penetration and cellular uptake, including crossing of the blood–brain barrier (BBB) to reach targets in the central nervous system (CNS). For SMA application, we have investigated the ability of various BBB-crossing peptides for CNS delivery of a splice-switching phosphorodiamidate morpholino oligonucleotide (PMO) targeting survival motor neuron 2 (SMN2) exon 7 inclusion. We identified a branched derivative of the well-known ApoE (141–150) peptide, which as a PMO conjugate was capable of exon inclusion in the CNS following systemic administration, leading to an increase in the level of full-length SMN2 transcript. Treatment of newborn SMA mice with this peptide-PMO (P-PMO) conjugate resulted in a significant increase in the average lifespan and gains in weight, muscle strength, and righting reflexes. Systemic treatment of adult SMA mice with this newly identified P-PMO also resulted in small but significant increases in the levels of SMN2 pre-messenger RNA (mRNA) exon inclusion in the CNS and peripheral tissues. This work provides proof of principle for the ability to select new peptide paradigms to enhance CNS delivery and activity of a PMO SSO through use of a peptide-based delivery platform for the treatment of SMA potentially extending to other neuromuscular and neurodegenerative diseases.",2017 Jun 1,"['Shabanpoor, Fazel', 'Hammond, Suzan M', 'Abendroth, Frank', 'Hazell, Gareth', 'Wood, Matthew J.A.', 'Gait, Michael J.']",Nucleic Acid Ther,,,True
08ac8987e585268b0664efc52bc4abbfda31249d,PMC,Identification of a Peptide for Systemic Brain Delivery of a Morpholino Oligonucleotide in Mouse Models of Spinal Muscular Atrophy,http://dx.doi.org/10.1089/nat.2016.0652,PMC5467147,28118087,NO-CC CODE,"Splice-switching antisense oligonucleotides are emerging treatments for neuromuscular diseases, with several splice-switching oligonucleotides (SSOs) currently undergoing clinical trials such as for Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). However, the development of systemically delivered antisense therapeutics has been hampered by poor tissue penetration and cellular uptake, including crossing of the blood–brain barrier (BBB) to reach targets in the central nervous system (CNS). For SMA application, we have investigated the ability of various BBB-crossing peptides for CNS delivery of a splice-switching phosphorodiamidate morpholino oligonucleotide (PMO) targeting survival motor neuron 2 (SMN2) exon 7 inclusion. We identified a branched derivative of the well-known ApoE (141–150) peptide, which as a PMO conjugate was capable of exon inclusion in the CNS following systemic administration, leading to an increase in the level of full-length SMN2 transcript. Treatment of newborn SMA mice with this peptide-PMO (P-PMO) conjugate resulted in a significant increase in the average lifespan and gains in weight, muscle strength, and righting reflexes. Systemic treatment of adult SMA mice with this newly identified P-PMO also resulted in small but significant increases in the levels of SMN2 pre-messenger RNA (mRNA) exon inclusion in the CNS and peripheral tissues. This work provides proof of principle for the ability to select new peptide paradigms to enhance CNS delivery and activity of a PMO SSO through use of a peptide-based delivery platform for the treatment of SMA potentially extending to other neuromuscular and neurodegenerative diseases.",2017 Jun 1,"['Shabanpoor, Fazel', 'Hammond, Suzan M', 'Abendroth, Frank', 'Hazell, Gareth', 'Wood, Matthew J.A.', 'Gait, Michael J.']",Nucleic Acid Ther,,,True
b62751438aa94a45829290ba4e6144afc95f4755,PMC,A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis,http://dx.doi.org/10.1038/nature22337,PMC5473467,28562588,NO-CC CODE,"Diarrheal disease is responsible for 8.6% of global child mortality. Recent epidemiological studies found the protozoan parasite Cryptosporidium to be a leading cause of pediatric diarrhea with particularly grave impact on infants and immunocompromised individuals. There is neither a vaccine nor effective treatment. We establish a drug discovery process built on scalable phenotypic assays and mouse models that takes advantage of transgenic parasites. Screening a library of compounds with anti-parasitic activity we identified pyrazolopyridines as inhibitors of Cryptosporidium parvum and C. hominis. Oral treatment with the pyrazolopyridine KDU731 results in potent reduction in intestinal infection of immunocompromised mice. Treatment also leads to rapid resolution of diarrhea and dehydration in neonatal calves, a clinical model of cryptosporidiosis that closely resembles human infection. Our results suggest the Cryptosporidium lipid kinase PI(4)K as a target for pyrazolopyridines and warrant further preclinical evaluation of KDU731 as a drug candidate for the treatment of cryptosporidiosis.",2017 Jun 15,"['Manjunatha, Ujjini H.', 'Vinayak, Sumiti', 'Zambriski, Jennifer A.', 'Chao, Alexander T.', 'Sy, Tracy', 'Noble, Christian G.', 'Bonamy, Ghislain M.C.', 'Kondreddi, Ravinder R.', 'Zou, Bin', 'Gedeck, Peter', 'Brooks, Carrie F.', 'Herbert, Gillian T.', 'Sateriale, Adam', 'Tandel, Jayesh', 'Noh, Susan', 'Lakshminarayana, Suresh B.', 'Lim, Siau H.', 'Goodman, Laura B.', 'Bodenreider, Christophe', 'Feng, Gu', 'Zhang, Lijun', 'Blasco, Francesca', 'Wagner, Juergen', 'Leong, F. Joel', 'Striepen, Boris', 'Diagana, Thierry T.']",Nature,,,True
144e23881b2b4c8852c4a615c4241b3d9e54b142,PMC,A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis,http://dx.doi.org/10.1038/nature22337,PMC5473467,28562588,NO-CC CODE,"Diarrheal disease is responsible for 8.6% of global child mortality. Recent epidemiological studies found the protozoan parasite Cryptosporidium to be a leading cause of pediatric diarrhea with particularly grave impact on infants and immunocompromised individuals. There is neither a vaccine nor effective treatment. We establish a drug discovery process built on scalable phenotypic assays and mouse models that takes advantage of transgenic parasites. Screening a library of compounds with anti-parasitic activity we identified pyrazolopyridines as inhibitors of Cryptosporidium parvum and C. hominis. Oral treatment with the pyrazolopyridine KDU731 results in potent reduction in intestinal infection of immunocompromised mice. Treatment also leads to rapid resolution of diarrhea and dehydration in neonatal calves, a clinical model of cryptosporidiosis that closely resembles human infection. Our results suggest the Cryptosporidium lipid kinase PI(4)K as a target for pyrazolopyridines and warrant further preclinical evaluation of KDU731 as a drug candidate for the treatment of cryptosporidiosis.",2017 Jun 15,"['Manjunatha, Ujjini H.', 'Vinayak, Sumiti', 'Zambriski, Jennifer A.', 'Chao, Alexander T.', 'Sy, Tracy', 'Noble, Christian G.', 'Bonamy, Ghislain M.C.', 'Kondreddi, Ravinder R.', 'Zou, Bin', 'Gedeck, Peter', 'Brooks, Carrie F.', 'Herbert, Gillian T.', 'Sateriale, Adam', 'Tandel, Jayesh', 'Noh, Susan', 'Lakshminarayana, Suresh B.', 'Lim, Siau H.', 'Goodman, Laura B.', 'Bodenreider, Christophe', 'Feng, Gu', 'Zhang, Lijun', 'Blasco, Francesca', 'Wagner, Juergen', 'Leong, F. Joel', 'Striepen, Boris', 'Diagana, Thierry T.']",Nature,,,False
17157c3f05df10f457da9123e14ddeffc0761c05,PMC,A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis,http://dx.doi.org/10.1038/nature22337,PMC5473467,28562588,NO-CC CODE,"Diarrheal disease is responsible for 8.6% of global child mortality. Recent epidemiological studies found the protozoan parasite Cryptosporidium to be a leading cause of pediatric diarrhea with particularly grave impact on infants and immunocompromised individuals. There is neither a vaccine nor effective treatment. We establish a drug discovery process built on scalable phenotypic assays and mouse models that takes advantage of transgenic parasites. Screening a library of compounds with anti-parasitic activity we identified pyrazolopyridines as inhibitors of Cryptosporidium parvum and C. hominis. Oral treatment with the pyrazolopyridine KDU731 results in potent reduction in intestinal infection of immunocompromised mice. Treatment also leads to rapid resolution of diarrhea and dehydration in neonatal calves, a clinical model of cryptosporidiosis that closely resembles human infection. Our results suggest the Cryptosporidium lipid kinase PI(4)K as a target for pyrazolopyridines and warrant further preclinical evaluation of KDU731 as a drug candidate for the treatment of cryptosporidiosis.",2017 Jun 15,"['Manjunatha, Ujjini H.', 'Vinayak, Sumiti', 'Zambriski, Jennifer A.', 'Chao, Alexander T.', 'Sy, Tracy', 'Noble, Christian G.', 'Bonamy, Ghislain M.C.', 'Kondreddi, Ravinder R.', 'Zou, Bin', 'Gedeck, Peter', 'Brooks, Carrie F.', 'Herbert, Gillian T.', 'Sateriale, Adam', 'Tandel, Jayesh', 'Noh, Susan', 'Lakshminarayana, Suresh B.', 'Lim, Siau H.', 'Goodman, Laura B.', 'Bodenreider, Christophe', 'Feng, Gu', 'Zhang, Lijun', 'Blasco, Francesca', 'Wagner, Juergen', 'Leong, F. Joel', 'Striepen, Boris', 'Diagana, Thierry T.']",Nature,,,False
0746647069ab1d117996a1f4468e4068629e6da6,PMC,Building Qatar severe respiratory failure ECMO program,http://dx.doi.org/10.5339/qmj.2017.swacelso.2,PMC5474570,,NO-CC CODE,,2017 Feb 14,"['Hassan, Ibrahim Mohamed Fawzy', 'Al Shaikh, Loua']",Qatar Med J,,,True
3c928eef1ab9e10c33a73c0dec240b088b82c06f,PMC,ECMO retrieval: A case for Critical Care Paramedic integration into the team,http://dx.doi.org/10.5339/qmj.2017.swacelso.5,PMC5474573,,NO-CC CODE,,2017 Feb 14,"Campbell, Craig B.",Qatar Med J,,,True
b3c9cb39f0bb957864906c7710cbbc349380face,PMC,"Qatar ECMO program: Past, present, and future",http://dx.doi.org/10.5339/qmj.2017.swacelso.10,PMC5474578,,NO-CC CODE,,2017 Feb 14,"['Hassan, Ibrahim Fawzy', 'Al Shaikh, Loua']",Qatar Med J,,,True
410a3623ec545b80542d885b2c66848466c43c7c,PMC,Extracorporeal membrane oxygenation for systemic lupus erythematosus (SLE) with severe ARDS,http://dx.doi.org/10.5339/qmj.2017.swacelso.73,PMC5474641,,NO-CC CODE,,2017 Feb 14,"['Abdelaty, Mohamed', 'Fawzy, Ibrahim', 'Raza, Tasleem', 'Hssain, Ali Ait']",Qatar Med J,,,True
e29e17f37924d1d14edf56276a5dcca87851e62f,PMC,HIV-1 Frameshift RNA-Targeted Triazoles Inhibit Propagation of Replication-Competent and Multi-Drug-Resistant HIV in Human Cells,http://dx.doi.org/10.1021/acschembio.7b00052,PMC5477779,28448121,NO-CC CODE,"[Image: see text] The HIV-1 frameshift-stimulating (FSS) RNA, a regulatory RNA of critical importance in the virus’ life cycle, has been posited as a novel target for anti-HIV drug development. We report the synthesis and evaluation of triazole-containing compounds able to bind the FSS with high affinity and selectivity. Readily accessible synthetically, these compounds are less toxic than previously reported olefin congeners. We show for the first time that FSS-targeting compounds have antiviral activity against replication-competent HIV in human cells, including a highly cytopathic, multidrug-resistant strain. These results support the viability of the HIV-1 FSS RNA as a therapeutic target and more generally highlight opportunities for synthetic molecule-mediated interference with protein recoding in a wide range of organisms.",2017 Jun 16,"['Hilimire, Thomas\nA.', 'Chamberlain, Jeffrey M.', 'Anokhina, Viktoriya', 'Bennett, Ryan P.', 'Swart, Oliver', 'Myers, Jason R.', 'Ashton, John M.', 'Stewart, Ryan A.', 'Featherston, Aaron L.', 'Gates, Kathleen', 'Helms, Eric D.', 'Smith, Harold C.', 'Dewhurst, Stephen', 'Miller, Benjamin L.']",ACS Chem Biol,,,True
ec7973e6d8b97caf18e06fa5b0150b47157fe45a,PMC,HIV-1 Frameshift RNA-Targeted Triazoles Inhibit Propagation of Replication-Competent and Multi-Drug-Resistant HIV in Human Cells,http://dx.doi.org/10.1021/acschembio.7b00052,PMC5477779,28448121,NO-CC CODE,"[Image: see text] The HIV-1 frameshift-stimulating (FSS) RNA, a regulatory RNA of critical importance in the virus’ life cycle, has been posited as a novel target for anti-HIV drug development. We report the synthesis and evaluation of triazole-containing compounds able to bind the FSS with high affinity and selectivity. Readily accessible synthetically, these compounds are less toxic than previously reported olefin congeners. We show for the first time that FSS-targeting compounds have antiviral activity against replication-competent HIV in human cells, including a highly cytopathic, multidrug-resistant strain. These results support the viability of the HIV-1 FSS RNA as a therapeutic target and more generally highlight opportunities for synthetic molecule-mediated interference with protein recoding in a wide range of organisms.",2017 Jun 16,"['Hilimire, Thomas\nA.', 'Chamberlain, Jeffrey M.', 'Anokhina, Viktoriya', 'Bennett, Ryan P.', 'Swart, Oliver', 'Myers, Jason R.', 'Ashton, John M.', 'Stewart, Ryan A.', 'Featherston, Aaron L.', 'Gates, Kathleen', 'Helms, Eric D.', 'Smith, Harold C.', 'Dewhurst, Stephen', 'Miller, Benjamin L.']",ACS Chem Biol,,,True
0c3220694f8a18b6dcd64afae28c4784190e4ee6,PMC,"A molecular beacon, bead-based assay for the detection of nucleic acids by flow cytometry",http://dx.doi.org/10.1093/nar/gni015,PMC548373,15659574,NO-CC CODE,"Molecular beacons are dual-labelled probes that are typically used in real-time PCR assays, but have also been conjugated with solid matrices for use in microarrays or biosensors. We have developed a fluid array system using microsphere-conjugated molecular beacons and the flow cytometer for the specific, multiplexed detection of unlabelled nucleic acids in solution. For this array system, molecular beacons were conjugated with microspheres using a biotin-streptavidin linkage. A bridged conjugation method using streptavidin increased the signal-to-noise ratio, allowing for further discrimination of target quantitation. Using beads of different sizes and molecular beacons in two fluorophore colours, synthetic nucleic acid control sequences were specifically detected for three respiratory pathogens, including the SARS coronavirus in proof-of-concept experiments. Considering that routine flow cytometers are able to detect up to four fluorescent channels, this novel assay may allow for the specific multiplex detection of a nucleic acid panel in a single tube.",2005 Jan 19,"['Horejsh, Douglas', 'Martini, Federico', 'Poccia, Fabrizio', 'Ippolito, Giuseppe', 'Di Caro, Antonino', 'Capobianchi, Maria R.']",Nucleic Acids Res,,,True
1de19b32c96620e4a961d3bb006f5b0d2c233eea,PMC,"A molecular beacon, bead-based assay for the detection of nucleic acids by flow cytometry",http://dx.doi.org/10.1093/nar/gni015,PMC548373,15659574,NO-CC CODE,"Molecular beacons are dual-labelled probes that are typically used in real-time PCR assays, but have also been conjugated with solid matrices for use in microarrays or biosensors. We have developed a fluid array system using microsphere-conjugated molecular beacons and the flow cytometer for the specific, multiplexed detection of unlabelled nucleic acids in solution. For this array system, molecular beacons were conjugated with microspheres using a biotin-streptavidin linkage. A bridged conjugation method using streptavidin increased the signal-to-noise ratio, allowing for further discrimination of target quantitation. Using beads of different sizes and molecular beacons in two fluorophore colours, synthetic nucleic acid control sequences were specifically detected for three respiratory pathogens, including the SARS coronavirus in proof-of-concept experiments. Considering that routine flow cytometers are able to detect up to four fluorescent channels, this novel assay may allow for the specific multiplex detection of a nucleic acid panel in a single tube.",2005 Jan 19,"['Horejsh, Douglas', 'Martini, Federico', 'Poccia, Fabrizio', 'Ippolito, Giuseppe', 'Di Caro, Antonino', 'Capobianchi, Maria R.']",Nucleic Acids Res,,,False
867e1b0f6ca8757f2a32a625d99b23888ab40d49,PMC,"Comparisons of substitution, insertion and deletion probes for resequencing and mutational analysis using oligonucleotide microarrays",http://dx.doi.org/10.1093/nar/gni034,PMC549431,15722479,NO-CC CODE,"Although oligonucleotide probes complementary to single nucleotide substitutions are commonly used in microarray-based screens for genetic variation, little is known about the hybridization properties of probes complementary to small insertions and deletions. It is necessary to define the hybridization properties of these latter probes in order to improve the specificity and sensitivity of oligonucleotide microarray-based mutational analysis of disease-related genes. Here, we compare and contrast the hybridization properties of oligonucleotide microarrays consisting of 25mer probes complementary to all possible single nucleotide substitutions and insertions, and one and two base deletions in the 9168 bp coding region of the ATM (ataxia telangiectasia mutated) gene. Over 68 different dye-labeled single-stranded nucleic acid targets representing all ATM coding exons were applied to these microarrays. We assess hybridization specificity by comparing the relative hybridization signals from probes perfectly matched to ATM sequences to those containing mismatches. Probes complementary to two base substitutions displayed the highest average specificity followed by those complementary to single base substitutions, single base deletions and single base insertions. In all the cases, hybridization specificity was strongly influenced by sequence context and possible intra- and intermolecular probe and/or target structure. Furthermore, single nucleotide substitution probes displayed the most consistent hybridization specificity data followed by single base deletions, two base deletions and single nucleotide insertions. Overall, these studies provide valuable empirical data that can be used to more accurately model the hybridization properties of insertion and deletion probes and improve the design and interpretation of oligonucleotide microarray-based resequencing and mutational analysis.",2005 Feb 18,"['Karaman, Mazen W.', 'Groshen, Susan', 'Lee, Chi-Chiang', 'Pike, Brian L.', 'Hacia, Joseph G.']",Nucleic Acids Res,,,True
77fd0472e928d4de06d38d23f069467e0bc6b4c0,PMC,"Porcine Hemagglutinating Encephalomyelitis Virus and Respiratory Disease in Exhibition Swine, Michigan, USA, 2015",http://dx.doi.org/10.3201/eid2307.170019,PMC5512476,28628449,NO-CC CODE,"Acute outbreaks of respiratory disease in swine at agricultural fairs in Michigan, USA, in 2015 raised concern for potential human exposure to influenza A virus. Testing ruled out influenza A virus and identified porcine hemagglutinating encephalomyelitis virus as the cause of influenza-like illness in the affected swine.",2017 Jul,"['Lorbach, Joshua N.', 'Wang, Leyi', 'Nolting, Jacqueline M.', 'Benjamin, Madonna G.', 'Killian, Mary Lea', 'Zhang, Yan', 'Bowman, Andrew S.']",Emerg Infect Dis,,,True
84f1f12eb12aa3a677a3c0efb7417a17d0ac3adc,PMC,"Porcine Hemagglutinating Encephalomyelitis Virus and Respiratory Disease in Exhibition Swine, Michigan, USA, 2015",http://dx.doi.org/10.3201/eid2307.170019,PMC5512476,28628449,NO-CC CODE,"Acute outbreaks of respiratory disease in swine at agricultural fairs in Michigan, USA, in 2015 raised concern for potential human exposure to influenza A virus. Testing ruled out influenza A virus and identified porcine hemagglutinating encephalomyelitis virus as the cause of influenza-like illness in the affected swine.",2017 Jul,"['Lorbach, Joshua N.', 'Wang, Leyi', 'Nolting, Jacqueline M.', 'Benjamin, Madonna G.', 'Killian, Mary Lea', 'Zhang, Yan', 'Bowman, Andrew S.']",Emerg Infect Dis,,,True
244a3bd441bc1a9400a8529ed9933ae8a1f8d00a,PMC,"MERS-CoV Antibody Responses 1 Year after Symptom Onset, South Korea, 2015",http://dx.doi.org/10.3201/eid2307.170310,PMC5512479,28585916,NO-CC CODE,"We investigated the kinetics of the Middle East respiratory syndrome coronavirus (MERS-CoV) neutralizing and spike protein antibody titers over the course of 1 year in 11 patients who were confirmed by reverse transcription PCR to have been infected during the outbreak in South Korea in 2015. Robust antibody responses were detected in all survivors who had severe disease; responses remained detectable, albeit with some waning, for <1 year. The duration of viral RNA detection (but not viral load) in sputum significantly correlated with the antibody response magnitude. The MERS S1 ELISA antibody titers correlated well with the neutralizing antibody response. Antibody titers in 4 of 6 patients who had mild illness were undetectable even though most had evidence of pneumonia. This finding implies that MERS-CoV seroepidemiologic studies markedly underestimate the extent of mild and asymptomatic infection. Obtaining convalescent-phase plasma with high antibody titers to treat MERS will be challenging.",2017 Jul,"['Choe, Pyoeng Gyun', 'Perera, R.A.P.M.', 'Park, Wan Beom', 'Song, Kyoung-Ho', 'Bang, Ji Hwan', 'Kim, Eu Suk', 'Kim, Hong Bin', 'Ko, Long Wei Ronald', 'Park, Sang Won', 'Kim, Nam-Joong', 'Lau, Eric H.Y.', 'Poon, Leo L.M.', 'Peiris, Malik', 'Oh, Myoung-don']",Emerg Infect Dis,,,True
564a55d4015802e5b59bcd447545144a2474a91a,PMC,"MERS-CoV Antibody Responses 1 Year after Symptom Onset, South Korea, 2015",http://dx.doi.org/10.3201/eid2307.170310,PMC5512479,28585916,NO-CC CODE,"We investigated the kinetics of the Middle East respiratory syndrome coronavirus (MERS-CoV) neutralizing and spike protein antibody titers over the course of 1 year in 11 patients who were confirmed by reverse transcription PCR to have been infected during the outbreak in South Korea in 2015. Robust antibody responses were detected in all survivors who had severe disease; responses remained detectable, albeit with some waning, for <1 year. The duration of viral RNA detection (but not viral load) in sputum significantly correlated with the antibody response magnitude. The MERS S1 ELISA antibody titers correlated well with the neutralizing antibody response. Antibody titers in 4 of 6 patients who had mild illness were undetectable even though most had evidence of pneumonia. This finding implies that MERS-CoV seroepidemiologic studies markedly underestimate the extent of mild and asymptomatic infection. Obtaining convalescent-phase plasma with high antibody titers to treat MERS will be challenging.",2017 Jul,"['Choe, Pyoeng Gyun', 'Perera, R.A.P.M.', 'Park, Wan Beom', 'Song, Kyoung-Ho', 'Bang, Ji Hwan', 'Kim, Eu Suk', 'Kim, Hong Bin', 'Ko, Long Wei Ronald', 'Park, Sang Won', 'Kim, Nam-Joong', 'Lau, Eric H.Y.', 'Poon, Leo L.M.', 'Peiris, Malik', 'Oh, Myoung-don']",Emerg Infect Dis,,,False
203339b042e51e4489fd7a1ffd7911a5443b9a82,PMC,"Haemophilus influenzae Type a Meningitis in Immunocompetent Child, Oman, 2015",http://dx.doi.org/10.3201/eid2307.170311,PMC5512487,28628438,NO-CC CODE,"Meningitis caused by Haemophilus influenzae type b (Hib) was eliminated in Oman after the introduction of Hib vaccine in 2001. However, a case of H. influenzae type a meningitis was diagnosed in a child from Oman in 2015, which highlights the need to monitor the incidence of invasive non-Hib H. influenzae disease.",2017 Jul,"Sawardekar, Kiran P.",Emerg Infect Dis,,,True
d78a4422073df5f7ab9133d2f4374626f8f23672,PMC,"Haemophilus influenzae Type a Meningitis in Immunocompetent Child, Oman, 2015",http://dx.doi.org/10.3201/eid2307.170311,PMC5512487,28628438,NO-CC CODE,"Meningitis caused by Haemophilus influenzae type b (Hib) was eliminated in Oman after the introduction of Hib vaccine in 2001. However, a case of H. influenzae type a meningitis was diagnosed in a child from Oman in 2015, which highlights the need to monitor the incidence of invasive non-Hib H. influenzae disease.",2017 Jul,"Sawardekar, Kiran P.",Emerg Infect Dis,,,False
b022e6ee1e7b9a0a822b1255c2fa12f81ddc52fd,PMC,A Gene Encoding Sialic-Acid-Specific 9-O-Acetylesterase Found in Human Adult Testis,http://dx.doi.org/10.1155/S1110724304307084,PMC551583,15292578,NO-CC CODE,"Using differential display RT-PCR, we identified a gene of 2750 bp from human adult testis, named H-Lse, which encoded a putative protein of 523 amino acids and molecular weight of 58 kd with structural characteristics similar to that of mouse lysosome sialic-acid-specific 9-O-acetylesterase. Northern blot analysis showed a widespread distribution of H-Lse in various human tissues with high expression in the testis, prostate, and colon. In situ hybridization results showed that while H-Lse was not detected in embryonic testis, positive signals were found in spermatocytes but not spermatogonia in adult testis of human. The subcellular localization of H-Lse was visualized by green fluorescent protein (GFP) fused to the amino terminus of H-Lse, showing compartmentalization of H-Lse in large dense-core vesicles, presumably lysosomes, in the cytoplasm. The developmentally regulated and spermatogenic stage-specific expression of H-Lse suggests its possible involvement in the development of the testis and/or differentiation of germ cells.",2004 Jul 29,"['Zhu, Hu', 'Chang Chan, Hsiao', 'Zhou, Zuoming', 'Li, Jianming', 'Zhu, Hui', 'Yin, Lanlan', 'Xu, Ming', 'Cheng, Lijun', 'Sha, Jiahao']",J Biomed Biotechnol,,,True
c6aa166f4555bb78d415f1f6c0ba418ef6a59652,PMC,A novel neutralizing monoclonal antibody targeting the N-terminal domain of the MERS-CoV spike protein,http://dx.doi.org/10.1038/emi.2017.50,PMC5520321,28655936,NO-CC CODE,,2017 Jun 28,"['Chen, Yingzhu', 'Lu, Shuai', 'Jia, Hao', 'Deng, Yao', 'Zhou, Jianfang', 'Huang, Baoying', 'Yu, Yueyang', 'Lan, Jiaming', 'Wang, Wenling', 'Lou, Yongliang', 'Qin, Kun', 'Tan, Wenjie']",Emerg Microbes Infect,,,False
aeb2fd035cedb1adb0f4498c351310f5f2fea5a8,PMC,Open and Closed Structures Reveal Allostery and Pliability in the HIV-1 Envelope Spike,http://dx.doi.org/10.1038/nature23010,PMC5538736,28700571,NO-CC CODE,"For many enveloped viruses, binding to a receptor(s) on a host cell acts as a first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication [for review see(1,2)]. The envelope glycoprotein (Env) trimer on the surface of HIV is responsible for receptor binding and fusion. While Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness. Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env(3,4), targets of broadly neutralizing antibodies (bnAbs). Thus, they are attractive immunogens for vaccine development [for review see(5–8)]. Here we present high-resolution cryo-electron microscopy (cryoEM) structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of ~3.7 Å and ~3.6 Å, respectively, and compare them to cryoEM reconstructions of ligand-free B41 SOSIP Env trimers or in complex with either CD4 or CD4bs antibody PGV04, at ~5.6 Å, ~5.2 Å and ~7.4 Å, respectively. Consequently, we present the most complete description and understanding of the CD4/17b-induced intermediate and provide the molecular basis of the receptor-binding induced conformational change required for HIV-1 entry into host cells. Both CD4 and b12 induce large, previously uncharacterized conformational rearrangements in the gp41 subunits, and the fusion peptide becomes more buried in a newly formed pocket. These structures provide key details on the biological function of the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design.",2017 Jul 20,"['Ozorowski, Gabriel', 'Pallesen, Jesper', 'de Val, Natalia', 'Lyumkis, Dmitry', 'Cottrell, Christopher A.', 'Torres, Jonathan L.', 'Copps, Jeffrey', 'Stanfield, Robyn L.', 'Cupo, Albert', 'Pugach, Pavel', 'Moore, John P.', 'Wilson, Ian A.', 'Ward, Andrew B.']",Nature,,,True
79b3b568e3410a49377a23263dc326927d54e187,PMC,Extracting geographic locations from the literature for virus phylogeography using supervised and distant supervision methods,,PMC5543364,28815119,NO-CC CODE,"The field of phylogeography allows researchers to model the spread and evolution of viral genetic sequences. Phylogeography plays a major role in infectious disease surveillance, viral epidemiology and vaccine design. When conducting viral phylogeographic studies, researchers require the location of the infected host of the virus, which is often present in public databases such as GenBank. However, the geographic metadata in most GenBank records is not precise enough for many phylogeographic studies; therefore, researchers often need to search the articles linked to the records for more information, which can be a tedious process. Here, we describe two approaches for automatically detecting geographic location mentions in articles pertaining to virus-related GenBank records: a supervised sequence labeling approach with innovative features and a distant-supervision approach with novel noise- reduction methods. Evaluated on a manually annotated gold standard, our supervised sequence labeling and distant supervision approaches attained F-scores of 0.81 and 0.66, respectively.",2017 Jul 26,"['Weissenbacher, Davy', 'Sarker, Abeed', 'Tahsin, Tasnia', 'Scotch, Matthew', 'Gonzalez, Graciela']",AMIA Jt Summits Transl Sci Proc,,,True
12e736a64e6f0562c5360b81802cb2641033a769,PMC,"Human Metapneumovirus and Other Respiratory Viral Infections during Pregnancy and Birth, Nepal",http://dx.doi.org/10.3201/eid2308.161358,PMC5547777,28726613,NO-CC CODE,"Human metapneumovirus (HMPV) is a respiratory virus that can cause severe lower respiratory tract disease and even death, primarily in young children. The incidence and characteristics of HMPV have not been well described in pregnant women. As part of a trial of maternal influenza immunization in rural southern Nepal, we conducted prospective, longitudinal, home-based active surveillance for febrile respiratory illness during pregnancy through 6 months postpartum. During 2011–2014, HMPV was detected in 55 of 3,693 women (16.4 cases/1,000 person-years). Twenty-five women were infected with HMPV during pregnancy, compared with 98 pregnant women who contracted rhinovirus and 7 who contracted respiratory syncytial virus. Women with HMPV during pregnancy had an increased risk of giving birth to infants who were small for gestational age. An intervention to reduce HMPV febrile respiratory illness in pregnant women may have the potential to decrease risk of adverse birth outcomes in developing countries.",2017 Aug,"['Lenahan, Jennifer L.', 'Englund, Janet A.', 'Katz, Joanne', 'Kuypers, Jane', 'Wald, Anna', 'Magaret, Amalia', 'Tielsch, James M.', 'Khatry, Subarna K.', 'LeClerq, Stephen C.', 'Shrestha, Laxman', 'Steinhoff, Mark C.', 'Chu, Helen Y.']",Emerg Infect Dis,,,True
b4b8f10ccc235f72d842eec82c9e6f5a5afd56cc,PMC,Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola Virus in Rhesus Monkeys,http://dx.doi.org/10.1038/nature17180,PMC5551389,26934220,NO-CC CODE,"The most recent Ebola virus outbreak in West Africa – unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected – highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae(1). No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we describe the discovery of a novel anti-EBOV small molecule antiviral, GS-5734, a monophosphoramidate prodrug of an adenosine analog. GS-5734 exhibits antiviral activity against multiple variants of EBOV in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternate substrate and RNA-chain terminator in primer-extension assays utilizing a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life = 14 h) and distribution to sanctuary sites for viral replication including testes, eye, and brain. In a rhesus monkey model of EVD, once daily intravenous administration of 10 mg/kg GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two of six treated animals. These results provide the first substantive, post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses – including filoviruses, arenaviruses, and coronaviruses – suggests the potential for expanded indications. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing.",2016 Mar 17,"['Warren, Travis K.', 'Jordan, Robert', 'Lo, Michael K.', 'Ray, Adrian S.', 'Mackman, Richard L.', 'Soloveva, Veronica', 'Siegel, Dustin', 'Perron, Michel', 'Bannister, Roy', 'Hui, Hon C.', 'Larson, Nate', 'Strickley, Robert', 'Wells, Jay', 'Stuthman, Kelly S.', 'Van Tongeren, Sean A.', 'Garza, Nicole L.', 'Donnelly, Ginger', 'Shurtleff, Amy C.', 'Retterer, Cary J.', 'Gharaibeh, Dima', 'Zamani, Rouzbeh', 'Kenny, Tara', 'Eaton, Brett P.', 'Grimes, Elizabeth', 'Welch, Lisa S.', 'Gomba, Laura', 'Wilhelmsen, Catherine L.', 'Nichols, Donald K.', 'Nuss, Jonathan E.', 'Nagle, Elyse R.', 'Kugelman, Jeffrey R.', 'Palacios, Gustavo', 'Doerffler, Edward', 'Neville, Sean', 'Carra, Ernest', 'Clarke, Michael O.', 'Zhang, Lijun', 'Lew, Willard', 'Ross, Bruce', 'Wang, Queenie', 'Chun, Kwon', 'Wolfe, Lydia', 'Babusis, Darius', 'Park, Yeojin', 'Stray, Kirsten M.', 'Trancheva, Iva', 'Feng, Joy Y.', 'Baraskaus, Ona', 'Xu, Yili', 'Wong, Pamela', 'Braun, Molly R.', 'Flint, Mike', 'McMullan, Laura K.', 'Chen, Shan-Shan', 'Fearns, Rachel', 'Swaminathan, Swami', 'Mayers, Douglas L.', 'Spiropoulou, Christina F.', 'Lee, William A.', 'Nichol, Stuart T.', 'Cihlar, Tomas', 'Bavari, Sina']",Nature,,,True
030bcc13b2088bcfc2b1c2f6117e349e13f2e57b,PMC,Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola Virus in Rhesus Monkeys,http://dx.doi.org/10.1038/nature17180,PMC5551389,26934220,NO-CC CODE,"The most recent Ebola virus outbreak in West Africa – unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected – highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae(1). No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we describe the discovery of a novel anti-EBOV small molecule antiviral, GS-5734, a monophosphoramidate prodrug of an adenosine analog. GS-5734 exhibits antiviral activity against multiple variants of EBOV in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternate substrate and RNA-chain terminator in primer-extension assays utilizing a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life = 14 h) and distribution to sanctuary sites for viral replication including testes, eye, and brain. In a rhesus monkey model of EVD, once daily intravenous administration of 10 mg/kg GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two of six treated animals. These results provide the first substantive, post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses – including filoviruses, arenaviruses, and coronaviruses – suggests the potential for expanded indications. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing.",2016 Mar 17,"['Warren, Travis K.', 'Jordan, Robert', 'Lo, Michael K.', 'Ray, Adrian S.', 'Mackman, Richard L.', 'Soloveva, Veronica', 'Siegel, Dustin', 'Perron, Michel', 'Bannister, Roy', 'Hui, Hon C.', 'Larson, Nate', 'Strickley, Robert', 'Wells, Jay', 'Stuthman, Kelly S.', 'Van Tongeren, Sean A.', 'Garza, Nicole L.', 'Donnelly, Ginger', 'Shurtleff, Amy C.', 'Retterer, Cary J.', 'Gharaibeh, Dima', 'Zamani, Rouzbeh', 'Kenny, Tara', 'Eaton, Brett P.', 'Grimes, Elizabeth', 'Welch, Lisa S.', 'Gomba, Laura', 'Wilhelmsen, Catherine L.', 'Nichols, Donald K.', 'Nuss, Jonathan E.', 'Nagle, Elyse R.', 'Kugelman, Jeffrey R.', 'Palacios, Gustavo', 'Doerffler, Edward', 'Neville, Sean', 'Carra, Ernest', 'Clarke, Michael O.', 'Zhang, Lijun', 'Lew, Willard', 'Ross, Bruce', 'Wang, Queenie', 'Chun, Kwon', 'Wolfe, Lydia', 'Babusis, Darius', 'Park, Yeojin', 'Stray, Kirsten M.', 'Trancheva, Iva', 'Feng, Joy Y.', 'Baraskaus, Ona', 'Xu, Yili', 'Wong, Pamela', 'Braun, Molly R.', 'Flint, Mike', 'McMullan, Laura K.', 'Chen, Shan-Shan', 'Fearns, Rachel', 'Swaminathan, Swami', 'Mayers, Douglas L.', 'Spiropoulou, Christina F.', 'Lee, William A.', 'Nichol, Stuart T.', 'Cihlar, Tomas', 'Bavari, Sina']",Nature,,,False
ebaa3d997fcc4b0ba9d69664e4c11d76b7ab9ff1,PMC,Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola Virus in Rhesus Monkeys,http://dx.doi.org/10.1038/nature17180,PMC5551389,26934220,NO-CC CODE,"The most recent Ebola virus outbreak in West Africa – unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected – highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae(1). No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we describe the discovery of a novel anti-EBOV small molecule antiviral, GS-5734, a monophosphoramidate prodrug of an adenosine analog. GS-5734 exhibits antiviral activity against multiple variants of EBOV in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternate substrate and RNA-chain terminator in primer-extension assays utilizing a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life = 14 h) and distribution to sanctuary sites for viral replication including testes, eye, and brain. In a rhesus monkey model of EVD, once daily intravenous administration of 10 mg/kg GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two of six treated animals. These results provide the first substantive, post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses – including filoviruses, arenaviruses, and coronaviruses – suggests the potential for expanded indications. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing.",2016 Mar 17,"['Warren, Travis K.', 'Jordan, Robert', 'Lo, Michael K.', 'Ray, Adrian S.', 'Mackman, Richard L.', 'Soloveva, Veronica', 'Siegel, Dustin', 'Perron, Michel', 'Bannister, Roy', 'Hui, Hon C.', 'Larson, Nate', 'Strickley, Robert', 'Wells, Jay', 'Stuthman, Kelly S.', 'Van Tongeren, Sean A.', 'Garza, Nicole L.', 'Donnelly, Ginger', 'Shurtleff, Amy C.', 'Retterer, Cary J.', 'Gharaibeh, Dima', 'Zamani, Rouzbeh', 'Kenny, Tara', 'Eaton, Brett P.', 'Grimes, Elizabeth', 'Welch, Lisa S.', 'Gomba, Laura', 'Wilhelmsen, Catherine L.', 'Nichols, Donald K.', 'Nuss, Jonathan E.', 'Nagle, Elyse R.', 'Kugelman, Jeffrey R.', 'Palacios, Gustavo', 'Doerffler, Edward', 'Neville, Sean', 'Carra, Ernest', 'Clarke, Michael O.', 'Zhang, Lijun', 'Lew, Willard', 'Ross, Bruce', 'Wang, Queenie', 'Chun, Kwon', 'Wolfe, Lydia', 'Babusis, Darius', 'Park, Yeojin', 'Stray, Kirsten M.', 'Trancheva, Iva', 'Feng, Joy Y.', 'Baraskaus, Ona', 'Xu, Yili', 'Wong, Pamela', 'Braun, Molly R.', 'Flint, Mike', 'McMullan, Laura K.', 'Chen, Shan-Shan', 'Fearns, Rachel', 'Swaminathan, Swami', 'Mayers, Douglas L.', 'Spiropoulou, Christina F.', 'Lee, William A.', 'Nichol, Stuart T.', 'Cihlar, Tomas', 'Bavari, Sina']",Nature,,,False
450842232c176d0422a8d77300dec428f7c81d61,PMC,Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola Virus in Rhesus Monkeys,http://dx.doi.org/10.1038/nature17180,PMC5551389,26934220,NO-CC CODE,"The most recent Ebola virus outbreak in West Africa – unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected – highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae(1). No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we describe the discovery of a novel anti-EBOV small molecule antiviral, GS-5734, a monophosphoramidate prodrug of an adenosine analog. GS-5734 exhibits antiviral activity against multiple variants of EBOV in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternate substrate and RNA-chain terminator in primer-extension assays utilizing a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life = 14 h) and distribution to sanctuary sites for viral replication including testes, eye, and brain. In a rhesus monkey model of EVD, once daily intravenous administration of 10 mg/kg GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two of six treated animals. These results provide the first substantive, post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses – including filoviruses, arenaviruses, and coronaviruses – suggests the potential for expanded indications. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing.",2016 Mar 17,"['Warren, Travis K.', 'Jordan, Robert', 'Lo, Michael K.', 'Ray, Adrian S.', 'Mackman, Richard L.', 'Soloveva, Veronica', 'Siegel, Dustin', 'Perron, Michel', 'Bannister, Roy', 'Hui, Hon C.', 'Larson, Nate', 'Strickley, Robert', 'Wells, Jay', 'Stuthman, Kelly S.', 'Van Tongeren, Sean A.', 'Garza, Nicole L.', 'Donnelly, Ginger', 'Shurtleff, Amy C.', 'Retterer, Cary J.', 'Gharaibeh, Dima', 'Zamani, Rouzbeh', 'Kenny, Tara', 'Eaton, Brett P.', 'Grimes, Elizabeth', 'Welch, Lisa S.', 'Gomba, Laura', 'Wilhelmsen, Catherine L.', 'Nichols, Donald K.', 'Nuss, Jonathan E.', 'Nagle, Elyse R.', 'Kugelman, Jeffrey R.', 'Palacios, Gustavo', 'Doerffler, Edward', 'Neville, Sean', 'Carra, Ernest', 'Clarke, Michael O.', 'Zhang, Lijun', 'Lew, Willard', 'Ross, Bruce', 'Wang, Queenie', 'Chun, Kwon', 'Wolfe, Lydia', 'Babusis, Darius', 'Park, Yeojin', 'Stray, Kirsten M.', 'Trancheva, Iva', 'Feng, Joy Y.', 'Baraskaus, Ona', 'Xu, Yili', 'Wong, Pamela', 'Braun, Molly R.', 'Flint, Mike', 'McMullan, Laura K.', 'Chen, Shan-Shan', 'Fearns, Rachel', 'Swaminathan, Swami', 'Mayers, Douglas L.', 'Spiropoulou, Christina F.', 'Lee, William A.', 'Nichol, Stuart T.', 'Cihlar, Tomas', 'Bavari, Sina']",Nature,,,True
5486c2563d83a0e3ad74b1d703596bdceacc76b3,PMC,Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola Virus in Rhesus Monkeys,http://dx.doi.org/10.1038/nature17180,PMC5551389,26934220,NO-CC CODE,"The most recent Ebola virus outbreak in West Africa – unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected – highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae(1). No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we describe the discovery of a novel anti-EBOV small molecule antiviral, GS-5734, a monophosphoramidate prodrug of an adenosine analog. GS-5734 exhibits antiviral activity against multiple variants of EBOV in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternate substrate and RNA-chain terminator in primer-extension assays utilizing a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life = 14 h) and distribution to sanctuary sites for viral replication including testes, eye, and brain. In a rhesus monkey model of EVD, once daily intravenous administration of 10 mg/kg GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two of six treated animals. These results provide the first substantive, post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses – including filoviruses, arenaviruses, and coronaviruses – suggests the potential for expanded indications. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing.",2016 Mar 17,"['Warren, Travis K.', 'Jordan, Robert', 'Lo, Michael K.', 'Ray, Adrian S.', 'Mackman, Richard L.', 'Soloveva, Veronica', 'Siegel, Dustin', 'Perron, Michel', 'Bannister, Roy', 'Hui, Hon C.', 'Larson, Nate', 'Strickley, Robert', 'Wells, Jay', 'Stuthman, Kelly S.', 'Van Tongeren, Sean A.', 'Garza, Nicole L.', 'Donnelly, Ginger', 'Shurtleff, Amy C.', 'Retterer, Cary J.', 'Gharaibeh, Dima', 'Zamani, Rouzbeh', 'Kenny, Tara', 'Eaton, Brett P.', 'Grimes, Elizabeth', 'Welch, Lisa S.', 'Gomba, Laura', 'Wilhelmsen, Catherine L.', 'Nichols, Donald K.', 'Nuss, Jonathan E.', 'Nagle, Elyse R.', 'Kugelman, Jeffrey R.', 'Palacios, Gustavo', 'Doerffler, Edward', 'Neville, Sean', 'Carra, Ernest', 'Clarke, Michael O.', 'Zhang, Lijun', 'Lew, Willard', 'Ross, Bruce', 'Wang, Queenie', 'Chun, Kwon', 'Wolfe, Lydia', 'Babusis, Darius', 'Park, Yeojin', 'Stray, Kirsten M.', 'Trancheva, Iva', 'Feng, Joy Y.', 'Baraskaus, Ona', 'Xu, Yili', 'Wong, Pamela', 'Braun, Molly R.', 'Flint, Mike', 'McMullan, Laura K.', 'Chen, Shan-Shan', 'Fearns, Rachel', 'Swaminathan, Swami', 'Mayers, Douglas L.', 'Spiropoulou, Christina F.', 'Lee, William A.', 'Nichol, Stuart T.', 'Cihlar, Tomas', 'Bavari, Sina']",Nature,,,False
e92e2d8ab6aedfa9c7486162c9520e4ea4485df2,PMC,Host and viral traits predict zoonotic spillover from mammals,http://dx.doi.org/10.1038/nature22975,PMC5570460,28636590,NO-CC CODE,"The majority of human emerging infectious diseases (EIDs) are zoonotic, with viruses originating in wild mammals of particular concern (e.g. HIV, Ebola, SARS)(1–3). Understanding patterns of viral diversity in wildlife and determinants of successful cross-species transmission, or spillover, are therefore key goals for pandemic surveillance programs(4). However, few analytical tools exist to identify which host species likely harbor the next human virus, or which viruses can cross species boundaries(5–7). Here we conduct the most comprehensive analysis yet of mammalian host-virus relationships and show that both the total number of viruses that infect a given species, and the proportion likely to be zoonotic are predictable. After controlling for research effort, the proportion of zoonotic viruses per species is predicted by phylogenetic relatedness to humans, host taxonomy, and human population within a species range – which may reflect human-wildlife contact. We demonstrate for the first time that bats harbor a significantly higher proportion of zoonotic viruses than all other mammalian orders. We identify the taxa and geographic regions with the largest estimated number of ‘missing viruses’ and ‘missing zoonoses’ and therefore of highest value for future surveillance. We then show that phylogenetic host breadth and other viral traits are significant predictors of zoonotic potential, providing a novel framework to assess if a newly discovered mammalian virus could infect people.",2017 Jun 29,"['Olival, Kevin J.', 'Hosseini, Parviez R.', 'Zambrana-Torrelio, Carlos', 'Ross, Noam', 'Bogich, Tiffany L.', 'Daszak, Peter']",Nature,,,True
e2d91b039a8a0d8631126c4eea4b82ff4510c70f,PMC,"A New Bat-HKU2–like Coronavirus in Swine, China, 2017",http://dx.doi.org/10.3201/eid2309.170915,PMC5572857,28654418,NO-CC CODE,"We identified from suckling piglets with diarrhea in China a new bat-HKU2–like porcine coronavirus (porcine enteric alphacoronavirus). The GDS04 strain of this coronavirus shares high aa identities (>90%) with the reported bat-HKU2 strains in Coronaviridae-wide conserved domains, suggesting that the GDS04 strain belongs to the same species as HKU2.",2017 Sep,"['Gong, Lang', 'Li, Jie', 'Zhou, Qingfeng', 'Xu, Zhichao', 'Chen, Li', 'Zhang, Yun', 'Xue, Chunyi', 'Wen, Zhifen', 'Cao, Yongchang']",Emerg Infect Dis,,,True
f55b2931d9176d19dad45d49aa691957a8587317,PMC,"Serologic Evidence for Influenza C and D Virus among Ruminants and Camelids, Africa, 1991–2015",http://dx.doi.org/10.3201/eid2309.170342,PMC5572875,28820371,NO-CC CODE,"Influenza D virus has been identified in America, Europe, and Asia. We detected influenza D virus antibodies in cattle and small ruminants from North (Morocco) and West (Togo and Benin) Africa. Dromedary camels in Kenya harbored influenza C or D virus antibodies, indicating a potential new host for these viruses.",2017 Sep,"['Salem, Elias', 'Cook, Elizabeth A.J.', 'Lbacha, Hicham Ait', 'Oliva, Justine', 'Awoume, Félix', 'Aplogan, Gilbert L.', 'Hymann, Emmanuel Couacy', 'Muloi, Dishon', 'Deem, Sharon L.', 'Alali, Said', 'Zouagui, Zaid', 'Fèvre, Eric M.', 'Meyer, Gilles', 'Ducatez, Mariette F.']",Emerg Infect Dis,,,True
1afdb2fbad2a5cb21a3420d4af09352912633a8a,PMC,"Serologic Evidence for Influenza C and D Virus among Ruminants and Camelids, Africa, 1991–2015",http://dx.doi.org/10.3201/eid2309.170342,PMC5572875,28820371,NO-CC CODE,"Influenza D virus has been identified in America, Europe, and Asia. We detected influenza D virus antibodies in cattle and small ruminants from North (Morocco) and West (Togo and Benin) Africa. Dromedary camels in Kenya harbored influenza C or D virus antibodies, indicating a potential new host for these viruses.",2017 Sep,"['Salem, Elias', 'Cook, Elizabeth A.J.', 'Lbacha, Hicham Ait', 'Oliva, Justine', 'Awoume, Félix', 'Aplogan, Gilbert L.', 'Hymann, Emmanuel Couacy', 'Muloi, Dishon', 'Deem, Sharon L.', 'Alali, Said', 'Zouagui, Zaid', 'Fèvre, Eric M.', 'Meyer, Gilles', 'Ducatez, Mariette F.']",Emerg Infect Dis,,,True
8568798df5346bdd1ae349b11ae1d0160eaed6ba,PMC,"Conveyance Contact Investigation for Imported Middle East Respiratory Syndrome Cases, United States, May 2014",http://dx.doi.org/10.3201/eid2309.170365,PMC5572888,28820379,NO-CC CODE,"In 2014, the Centers for Disease Control and Prevention conducted conveyance contact investigations for 2 Middle East respiratory syndrome cases imported into the United States, comprising all passengers and crew on 4 international and domestic flights and 1 bus. Of 655 contacts, 78% were interviewed; 33% had serologic testing. No secondary cases were identified.",2017 Sep,"['Lippold, Susan A.', 'Objio, Tina', 'Vonnahme, Laura', 'Washburn, Faith', 'Cohen, Nicole J.', 'Chen, Tai-Ho', 'Edelson, Paul J.', 'Gulati, Reena', 'Hale, Christa', 'Harcourt, Jennifer', 'Haynes, Lia', 'Jewett, Amy', 'Jungerman, Robynne', 'Kohl, Katrin S.', 'Miao, Congrong', 'Pesik, Nicolette', 'Regan, Joanna J.', 'Roland, Efrosini', 'Schembri, Chris', 'Schneider, Eileen', 'Tamin, Azaibi', 'Tatti, Kathleen', 'Alvarado-Ramy, Francisco']",Emerg Infect Dis,,,True
de5e1374a67895eb515193eca9435d1ad8bce7e0,PMC,Determination of Ferret Enteric Coronavirus Genome in Laboratory Ferrets,http://dx.doi.org/10.3201/eid2309.160215,PMC5572892,28820366,NO-CC CODE,"Ferret enteric coronavirus (FRECV) RNA was detected in laboratory ferrets. Analysis of the complete genome sequence of 2 strains, FRCoV4370 and FRCoV063, revealed that FRECV shared 49.9%–68.9% nucleotide sequence identity with known coronaviruses. These results suggest that FRECV might be classified as a new species in the genus Alphacoronavirus.",2017 Sep,"['Li, Tian-Cheng', 'Yoshizaki, Sayaka', 'Kataoka, Michiyo', 'Doan, Yen Hai', 'Ami, Yasushi', 'Suzaki, Yuriko', 'Nakamura, Tomofumi', 'Takeda, Naokazu', 'Wakita, Takaji']",Emerg Infect Dis,,,True
d47bd477b5abdf117bc2e03d5ddfba990fc21e1b,PMC,Phylogenetic Insight into Zika and Emerging Viruses for a Perspective on Potential Hosts,http://dx.doi.org/10.1007/s10393-017-1237-x,PMC5596032,28421292,NO-CC CODE,"Global viral diversity is substantial, but viruses that contribute little to the public health burden or to agricultural damage receive minimal attention until a seemingly unimportant virus becomes a threat. The Zika virus (ZIKV) illustrated this, as there was limited information and awareness of the virus when it was identified as a public health emergency in February 2016. Predicting which virus may pose a future threat is difficult. This is in part because significant knowledge gaps in the basic biology and ecology of an emerging virus can impede policy development, delay decision making, and hinder public health action. We suggest using a phylogenetic framework of pathogens and their infected host species for insight into which animals may serve as reservoirs. For example, examining flaviviruses closely related to ZIKV, the phylogenetic framework indicates New World monkeys are the most likely candidates to be potential reservoirs for ZIKV. Secondarily, mammals that are in close proximity to humans should be considered because of the increased opportunity for pathogen exchange. The increase in human-mediated environmental change is accelerating the probability of another previously overlooked virus becoming a significant concern. By investing in basic science research and organizing our knowledge into an evolutionary framework, we will be better prepared to respond to the next emerging infectious disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10393-017-1237-x) contains supplementary material, which is available to authorized users.",2017 Apr 18,"['Weber, Diana S.', 'Alroy, Karen A.', 'Scheiner, Samuel M.']",Ecohealth,,,True
bf73a62e8d870d8edd2bd1fb2ca68424e2e8b7d9,PMC,Public antibodies to malaria antigens generated by two LAIR1 insertion modalities,http://dx.doi.org/10.1038/nature23670,PMC5635981,28847005,NO-CC CODE,"We previously described two donors in whom the extracellular domain of LAIR1, a collagen-binding inhibitory receptor encoded on chromosome 191, was inserted between the V and the DJ segments of an antibody. This insertion generated, through somatic mutations, broadly reactive antibodies against RIFINs, a type of variant antigen expressed on the surface of Plasmodium falciparum-infected erythrocytes (IEs)2. To investigate how frequently such antibodies are produced in response to malaria infection, we screened plasma from two large cohorts of individuals living in malaria-endemic regions. We report that 5-10% of malaria-exposed individuals, but none of the European blood donors tested, have high levels of LAIR1-containing antibodies that dominate the response to IEs without conferring enhanced protection against febrile malaria. By analyzing the antibody-producing B cell clones at the protein, cDNA and gDNA level, we characterized additional LAIR1 insertions between the V and DJ segments and discovered a second insertion modality whereby the LAIR1 exon encoding the extracellular domain and flanking intronic sequences are inserted into the switch region. By exon shuffling, this mechanism leads to the production of bispecific antibodies in which the LAIR1 domain is precisely positioned at the elbow between the VH and CH1 domains. Additionally, in one donor the gDNA encoding the VH and CH1 domains was deleted, leading to the production of a camel-like LAIR1-containing antibody. Sequencing of the switch regions of memory B cells from European blood donors revealed frequent templated inserts originating from transcribed genes that, in rare cases, comprised exons with orientation and frame compatible with expression. Collectively, these results reveal different modalities of LAIR1 insertion that lead to public and dominant antibodies against IEs and suggest that insertion of templated DNA represents an additional mechanism of antibody diversification that can be selected in the immune response against pathogens and exploited for B cell engineering.",2017 Aug 31,"['Pieper, Kathrin', 'Tan, Joshua', 'Piccoli, Luca', 'Foglierini, Mathilde', 'Barbieri, Sonia', 'Chen, Yiwei', 'Silacci-Fregni, Chiara', 'Wolf, Tobias', 'Jarrossay, David', 'Anderle, Marica', 'Abdi, Abdirahman', 'Ndungu, Francis M.', 'Doumbo, Ogobara K.', 'Traore, Boubacar', 'Tran, Tuan M.', 'Jongo, Said', 'Zenklusen, Isabelle', 'Crompton, Peter D.', 'Daubenberger, Claudia', 'Bull, Peter C.', 'Sallusto, Federica', 'Lanzavecchia, Antonio']",Nature,,,True
233b60dfe02f8c61b4a962657475c5bf8c72dfbd,PMC,Public antibodies to malaria antigens generated by two LAIR1 insertion modalities,http://dx.doi.org/10.1038/nature23670,PMC5635981,28847005,NO-CC CODE,"We previously described two donors in whom the extracellular domain of LAIR1, a collagen-binding inhibitory receptor encoded on chromosome 191, was inserted between the V and the DJ segments of an antibody. This insertion generated, through somatic mutations, broadly reactive antibodies against RIFINs, a type of variant antigen expressed on the surface of Plasmodium falciparum-infected erythrocytes (IEs)2. To investigate how frequently such antibodies are produced in response to malaria infection, we screened plasma from two large cohorts of individuals living in malaria-endemic regions. We report that 5-10% of malaria-exposed individuals, but none of the European blood donors tested, have high levels of LAIR1-containing antibodies that dominate the response to IEs without conferring enhanced protection against febrile malaria. By analyzing the antibody-producing B cell clones at the protein, cDNA and gDNA level, we characterized additional LAIR1 insertions between the V and DJ segments and discovered a second insertion modality whereby the LAIR1 exon encoding the extracellular domain and flanking intronic sequences are inserted into the switch region. By exon shuffling, this mechanism leads to the production of bispecific antibodies in which the LAIR1 domain is precisely positioned at the elbow between the VH and CH1 domains. Additionally, in one donor the gDNA encoding the VH and CH1 domains was deleted, leading to the production of a camel-like LAIR1-containing antibody. Sequencing of the switch regions of memory B cells from European blood donors revealed frequent templated inserts originating from transcribed genes that, in rare cases, comprised exons with orientation and frame compatible with expression. Collectively, these results reveal different modalities of LAIR1 insertion that lead to public and dominant antibodies against IEs and suggest that insertion of templated DNA represents an additional mechanism of antibody diversification that can be selected in the immune response against pathogens and exploited for B cell engineering.",2017 Aug 31,"['Pieper, Kathrin', 'Tan, Joshua', 'Piccoli, Luca', 'Foglierini, Mathilde', 'Barbieri, Sonia', 'Chen, Yiwei', 'Silacci-Fregni, Chiara', 'Wolf, Tobias', 'Jarrossay, David', 'Anderle, Marica', 'Abdi, Abdirahman', 'Ndungu, Francis M.', 'Doumbo, Ogobara K.', 'Traore, Boubacar', 'Tran, Tuan M.', 'Jongo, Said', 'Zenklusen, Isabelle', 'Crompton, Peter D.', 'Daubenberger, Claudia', 'Bull, Peter C.', 'Sallusto, Federica', 'Lanzavecchia, Antonio']",Nature,,,False
5df0eff67085765ddb57c2d6c684af9caef895e7,PMC,Public antibodies to malaria antigens generated by two LAIR1 insertion modalities,http://dx.doi.org/10.1038/nature23670,PMC5635981,28847005,NO-CC CODE,"We previously described two donors in whom the extracellular domain of LAIR1, a collagen-binding inhibitory receptor encoded on chromosome 191, was inserted between the V and the DJ segments of an antibody. This insertion generated, through somatic mutations, broadly reactive antibodies against RIFINs, a type of variant antigen expressed on the surface of Plasmodium falciparum-infected erythrocytes (IEs)2. To investigate how frequently such antibodies are produced in response to malaria infection, we screened plasma from two large cohorts of individuals living in malaria-endemic regions. We report that 5-10% of malaria-exposed individuals, but none of the European blood donors tested, have high levels of LAIR1-containing antibodies that dominate the response to IEs without conferring enhanced protection against febrile malaria. By analyzing the antibody-producing B cell clones at the protein, cDNA and gDNA level, we characterized additional LAIR1 insertions between the V and DJ segments and discovered a second insertion modality whereby the LAIR1 exon encoding the extracellular domain and flanking intronic sequences are inserted into the switch region. By exon shuffling, this mechanism leads to the production of bispecific antibodies in which the LAIR1 domain is precisely positioned at the elbow between the VH and CH1 domains. Additionally, in one donor the gDNA encoding the VH and CH1 domains was deleted, leading to the production of a camel-like LAIR1-containing antibody. Sequencing of the switch regions of memory B cells from European blood donors revealed frequent templated inserts originating from transcribed genes that, in rare cases, comprised exons with orientation and frame compatible with expression. Collectively, these results reveal different modalities of LAIR1 insertion that lead to public and dominant antibodies against IEs and suggest that insertion of templated DNA represents an additional mechanism of antibody diversification that can be selected in the immune response against pathogens and exploited for B cell engineering.",2017 Aug 31,"['Pieper, Kathrin', 'Tan, Joshua', 'Piccoli, Luca', 'Foglierini, Mathilde', 'Barbieri, Sonia', 'Chen, Yiwei', 'Silacci-Fregni, Chiara', 'Wolf, Tobias', 'Jarrossay, David', 'Anderle, Marica', 'Abdi, Abdirahman', 'Ndungu, Francis M.', 'Doumbo, Ogobara K.', 'Traore, Boubacar', 'Tran, Tuan M.', 'Jongo, Said', 'Zenklusen, Isabelle', 'Crompton, Peter D.', 'Daubenberger, Claudia', 'Bull, Peter C.', 'Sallusto, Federica', 'Lanzavecchia, Antonio']",Nature,,,False
d1419f840d41fa492861571bcd2b0d3d7f8dfaaa,PMC,Public antibodies to malaria antigens generated by two LAIR1 insertion modalities,http://dx.doi.org/10.1038/nature23670,PMC5635981,28847005,NO-CC CODE,"We previously described two donors in whom the extracellular domain of LAIR1, a collagen-binding inhibitory receptor encoded on chromosome 191, was inserted between the V and the DJ segments of an antibody. This insertion generated, through somatic mutations, broadly reactive antibodies against RIFINs, a type of variant antigen expressed on the surface of Plasmodium falciparum-infected erythrocytes (IEs)2. To investigate how frequently such antibodies are produced in response to malaria infection, we screened plasma from two large cohorts of individuals living in malaria-endemic regions. We report that 5-10% of malaria-exposed individuals, but none of the European blood donors tested, have high levels of LAIR1-containing antibodies that dominate the response to IEs without conferring enhanced protection against febrile malaria. By analyzing the antibody-producing B cell clones at the protein, cDNA and gDNA level, we characterized additional LAIR1 insertions between the V and DJ segments and discovered a second insertion modality whereby the LAIR1 exon encoding the extracellular domain and flanking intronic sequences are inserted into the switch region. By exon shuffling, this mechanism leads to the production of bispecific antibodies in which the LAIR1 domain is precisely positioned at the elbow between the VH and CH1 domains. Additionally, in one donor the gDNA encoding the VH and CH1 domains was deleted, leading to the production of a camel-like LAIR1-containing antibody. Sequencing of the switch regions of memory B cells from European blood donors revealed frequent templated inserts originating from transcribed genes that, in rare cases, comprised exons with orientation and frame compatible with expression. Collectively, these results reveal different modalities of LAIR1 insertion that lead to public and dominant antibodies against IEs and suggest that insertion of templated DNA represents an additional mechanism of antibody diversification that can be selected in the immune response against pathogens and exploited for B cell engineering.",2017 Aug 31,"['Pieper, Kathrin', 'Tan, Joshua', 'Piccoli, Luca', 'Foglierini, Mathilde', 'Barbieri, Sonia', 'Chen, Yiwei', 'Silacci-Fregni, Chiara', 'Wolf, Tobias', 'Jarrossay, David', 'Anderle, Marica', 'Abdi, Abdirahman', 'Ndungu, Francis M.', 'Doumbo, Ogobara K.', 'Traore, Boubacar', 'Tran, Tuan M.', 'Jongo, Said', 'Zenklusen, Isabelle', 'Crompton, Peter D.', 'Daubenberger, Claudia', 'Bull, Peter C.', 'Sallusto, Federica', 'Lanzavecchia, Antonio']",Nature,,,False
685eba5fefce2d8dff007fa996ecf065e56da933,PMC,Quantitative Temporal in Vivo Proteomics Deciphers the Transition of Virus-Driven Myeloid Cells into M2 Macrophages,http://dx.doi.org/10.1021/acs.jproteome.7b00425,PMC5648240,28768414,NO-CC CODE,"[Image: see text] Myeloid cells play a central role in the context of viral eradication, yet precisely how these cells differentiate throughout the course of acute infections is poorly understood. In this study, we have developed a novel quantitative temporal in vivo proteomics (QTiPs) platform to capture proteomic signatures of temporally transitioning virus-driven myeloid cells directly in situ, thus taking into consideration host–virus interactions throughout the course of an infection. QTiPs, in combination with phenotypic, functional, and metabolic analyses, elucidated a pivotal role for inflammatory CD11b(+), Ly6G(–), Ly6C(high-low) cells in antiviral immune response and viral clearance. Most importantly, the time-resolved QTiPs data set showed the transition of CD11b(+), Ly6G(–), Ly6C(high-low) cells into M2-like macrophages, which displayed increased antigen-presentation capacities and bioenergetic demands late in infection. We elucidated the pivotal role of myeloid cells in virus clearance and show how these cells phenotypically, functionally, and metabolically undergo a timely transition from inflammatory to M2-like macrophages in vivo. With respect to the growing appreciation for in vivo examination of viral–host interactions and for the role of myeloid cells, this study elucidates the use of quantitative proteomics to reveal the role and response of distinct immune cell populations throughout the course of virus infection.",2017 Sep 1,"['Clements, Derek\nR.', 'Murphy, John Patrick', 'Sterea, Andra', 'Kennedy, Barry E.', 'Kim, Youra', 'Helson, Erin', 'Almasi, Shekoufeh', 'Holay, Namit', 'Konda, Prathyusha', 'Paulo, Joao A.', 'Sharif, Tanveer', 'Lee, Patrick W.', 'Weekes, Michael P.', 'Gygi, Steven P.', 'Gujar, Shashi']",J Proteome Res,,,True
ca1a65f1df55811d14bb73bf71fb900b4f36a46a,PMC,Quantitative Temporal in Vivo Proteomics Deciphers the Transition of Virus-Driven Myeloid Cells into M2 Macrophages,http://dx.doi.org/10.1021/acs.jproteome.7b00425,PMC5648240,28768414,NO-CC CODE,"[Image: see text] Myeloid cells play a central role in the context of viral eradication, yet precisely how these cells differentiate throughout the course of acute infections is poorly understood. In this study, we have developed a novel quantitative temporal in vivo proteomics (QTiPs) platform to capture proteomic signatures of temporally transitioning virus-driven myeloid cells directly in situ, thus taking into consideration host–virus interactions throughout the course of an infection. QTiPs, in combination with phenotypic, functional, and metabolic analyses, elucidated a pivotal role for inflammatory CD11b(+), Ly6G(–), Ly6C(high-low) cells in antiviral immune response and viral clearance. Most importantly, the time-resolved QTiPs data set showed the transition of CD11b(+), Ly6G(–), Ly6C(high-low) cells into M2-like macrophages, which displayed increased antigen-presentation capacities and bioenergetic demands late in infection. We elucidated the pivotal role of myeloid cells in virus clearance and show how these cells phenotypically, functionally, and metabolically undergo a timely transition from inflammatory to M2-like macrophages in vivo. With respect to the growing appreciation for in vivo examination of viral–host interactions and for the role of myeloid cells, this study elucidates the use of quantitative proteomics to reveal the role and response of distinct immune cell populations throughout the course of virus infection.",2017 Sep 1,"['Clements, Derek\nR.', 'Murphy, John Patrick', 'Sterea, Andra', 'Kennedy, Barry E.', 'Kim, Youra', 'Helson, Erin', 'Almasi, Shekoufeh', 'Holay, Namit', 'Konda, Prathyusha', 'Paulo, Joao A.', 'Sharif, Tanveer', 'Lee, Patrick W.', 'Weekes, Michael P.', 'Gygi, Steven P.', 'Gujar, Shashi']",J Proteome Res,,,False
7d7255ec9a213b7fe04cb8c08b326e0aacd2fd9b,PMC,"Weather-Dependent Risk for Legionnaires’ Disease, United States",http://dx.doi.org/10.3201/eid2311.170137,PMC5652433,29048279,NO-CC CODE,"Using the Nationwide Inpatient Sample and US weather data, we estimated the probability of community-acquired pneumonia (CAP) being diagnosed as Legionnaires’ disease (LD). LD risk increases when weather is warm and humid. With warm weather, we found a dose-response relationship between relative humidity and the odds for LD. When the mean temperature was 60°–80°F with high humidity (>80.0%), the odds for CAP being diagnosed with LD were 3.1 times higher than with lower levels of humidity (<50.0%). Thus, in some regions (e.g., the Southwest), LD is rarely the cause of hospitalizations. In other regions and seasons (e.g., the mid-Atlantic in summer), LD is much more common. Thus, suspicion for LD should increase when weather is warm and humid. However, when weather is cold, dry, or extremely hot, empirically treating all CAP patients for LD might contribute to excessive antimicrobial drug use at a population level.",2017 Nov,"['Simmering, Jacob E.', 'Polgreen, Linnea A.', 'Hornick, Douglas B.', 'Sewell, Daniel K.', 'Polgreen, Philip M.']",Emerg Infect Dis,,,True
5010aea39e19c1442f458361abe37771ac76d697,PMC,Maintenance of PD-1 on brain-resident memory CD8 T cells is antigen-independent,http://dx.doi.org/10.1038/icb.2017.62,PMC5698165,28829048,NO-CC CODE,"Infection of the central nervous system by murine polyomavirus (MuPyV), a persistent natural mouse pathogen, establishes brain-resident memory CD8 T cells (bT(RM)) that uniformly and chronically express PD-1 irrespective of expression of the α(E) integrin CD103, a T(RM) cell marker. In contrast, memory antiviral CD8 T cells in the spleen are PD-1(−), despite viral loads being similar in both the brain and spleen during persistent infection. Repetitive antigen engagement is central to sustained PD-1 expression by T cells in chronic viral infections; however, recent evidence indicates that expression of inhibitory receptors, including PD-1 is part of the T(RM) differentiation program. Here, we asked whether PD-1 expression by CD8 bT(RM) cells during persistent MuPyV encephalitis is antigen-dependent. By transferring MuPyV-specific CD8 bT(RM) cells into brains of naive mice and mice infected with cognate epitope-sufficient and -deficient MuPyVs, we demonstrate that antigen and inflammation are dispensable for PD-1 maintenance. In vitro and direct ex vivo analyses indicate that CD103(−) MuPyV-specific CD8 bT(RM) retain functional competence. We further show that the Pdcd-1 promoter of anti-MuPyV bT(RM) cells is epigenetically fixed in a demethylated state in the brain. In contrast, the PD-1 promoter of splenic antiviral memory CD8 T cells undergoes remethylation after being demethylated during acute infection. These data show that PD-1 expression is an intrinsic property of brain T(RM) cells in a persistent CNS viral infection.",2017 Nov 22,"['Shwetank,', 'Abdelsamed, Hossam A.', 'Frost, Elizabeth L.', 'Schmitz, Heather M.', 'Mockus, Taryn E.', 'Youngblood, Ben A.', 'Lukacher, Aron E.']",Immunol Cell Biol,,,True
10e4ed78c900e76d6d0ad0a0042048fe3a8da25b,PMC,Maintenance of PD-1 on brain-resident memory CD8 T cells is antigen-independent,http://dx.doi.org/10.1038/icb.2017.62,PMC5698165,28829048,NO-CC CODE,"Infection of the central nervous system by murine polyomavirus (MuPyV), a persistent natural mouse pathogen, establishes brain-resident memory CD8 T cells (bT(RM)) that uniformly and chronically express PD-1 irrespective of expression of the α(E) integrin CD103, a T(RM) cell marker. In contrast, memory antiviral CD8 T cells in the spleen are PD-1(−), despite viral loads being similar in both the brain and spleen during persistent infection. Repetitive antigen engagement is central to sustained PD-1 expression by T cells in chronic viral infections; however, recent evidence indicates that expression of inhibitory receptors, including PD-1 is part of the T(RM) differentiation program. Here, we asked whether PD-1 expression by CD8 bT(RM) cells during persistent MuPyV encephalitis is antigen-dependent. By transferring MuPyV-specific CD8 bT(RM) cells into brains of naive mice and mice infected with cognate epitope-sufficient and -deficient MuPyVs, we demonstrate that antigen and inflammation are dispensable for PD-1 maintenance. In vitro and direct ex vivo analyses indicate that CD103(−) MuPyV-specific CD8 bT(RM) retain functional competence. We further show that the Pdcd-1 promoter of anti-MuPyV bT(RM) cells is epigenetically fixed in a demethylated state in the brain. In contrast, the PD-1 promoter of splenic antiviral memory CD8 T cells undergoes remethylation after being demethylated during acute infection. These data show that PD-1 expression is an intrinsic property of brain T(RM) cells in a persistent CNS viral infection.",2017 Nov 22,"['Shwetank,', 'Abdelsamed, Hossam A.', 'Frost, Elizabeth L.', 'Schmitz, Heather M.', 'Mockus, Taryn E.', 'Youngblood, Ben A.', 'Lukacher, Aron E.']",Immunol Cell Biol,,,False
0676519ecc7cd61639721c0d062615707f044506,PMC,"Lack of Secondary Transmission of Ebola Virus from Healthcare Worker to 238 Contacts, United Kingdom, December 2014",http://dx.doi.org/10.3201/eid2312.171100,PMC5708221,29148368,NO-CC CODE,"In December 2014, Ebola virus disease (EVD) was diagnosed in a healthcare worker in the United Kingdom after the worker returned from an Ebola treatment center in Sierra Leone. The worker flew on 2 flights during the early stages of disease. Follow-up of 238 contacts showed no evidence of secondary transmission of Ebola virus.",2017 Dec,"['Crook, Paul', 'Smith-Palmer, Alison', 'Maguire, Helen', 'McCarthy, Noel', 'Kirkbride, Hilary', 'Court, Bruce', 'Kanagarajah, Sanch', 'Turbitt, Deborah', 'Ahmed, Syed', 'Cosford, Paul', 'Oliver, Isabel']",Emerg Infect Dis,,,True
ba1b2eea863c7a93bdeb49f6062d3660b793e2c5,PMC,"Spread of Canine Influenza A(H3N2) Virus, United States",http://dx.doi.org/10.3201/eid2312.170246,PMC5708240,28858604,NO-CC CODE,"A canine influenza A(H3N2) virus emerged in the United States in February–March 2015, causing respiratory disease in dogs. The virus had previously been circulating among dogs in Asia, where it originated through the transfer of an avian-origin influenza virus around 2005 and continues to circulate. Sequence analysis suggests the US outbreak was initiated by a single introduction, in Chicago, of an H3N2 canine influenza virus circulating among dogs in South Korea in 2015. Despite local control measures, the virus has continued circulating among dogs in and around Chicago and has spread to several other areas of the country, particularly Georgia and North Carolina, although these secondary outbreaks appear to have ended within a few months. Some genetic variation has accumulated among the US viruses, with the appearance of regional-temporal lineages. The potential for interspecies transmission and zoonotic events involving this newly emerged influenza A virus is currently unknown.",2017 Dec,"['Voorhees, Ian E.H.', 'Glaser, Amy L.', 'Toohey-Kurth, Kathy', 'Newbury, Sandra', 'Dalziel, Benjamin D.', 'Dubovi, Edward J.', 'Poulsen, Keith', 'Leutenegger, Christian', 'Willgert, Katriina J.E.', 'Brisbane-Cohen, Laura', 'Richardson-Lopez, Jill', 'Holmes, Edward C.', 'Parrish, Colin R.']",Emerg Infect Dis,,,True
600034ef1d7af8c05ab1c4e6daf817525a6dafdb,PMC,"Spread of Canine Influenza A(H3N2) Virus, United States",http://dx.doi.org/10.3201/eid2312.170246,PMC5708240,28858604,NO-CC CODE,"A canine influenza A(H3N2) virus emerged in the United States in February–March 2015, causing respiratory disease in dogs. The virus had previously been circulating among dogs in Asia, where it originated through the transfer of an avian-origin influenza virus around 2005 and continues to circulate. Sequence analysis suggests the US outbreak was initiated by a single introduction, in Chicago, of an H3N2 canine influenza virus circulating among dogs in South Korea in 2015. Despite local control measures, the virus has continued circulating among dogs in and around Chicago and has spread to several other areas of the country, particularly Georgia and North Carolina, although these secondary outbreaks appear to have ended within a few months. Some genetic variation has accumulated among the US viruses, with the appearance of regional-temporal lineages. The potential for interspecies transmission and zoonotic events involving this newly emerged influenza A virus is currently unknown.",2017 Dec,"['Voorhees, Ian E.H.', 'Glaser, Amy L.', 'Toohey-Kurth, Kathy', 'Newbury, Sandra', 'Dalziel, Benjamin D.', 'Dubovi, Edward J.', 'Poulsen, Keith', 'Leutenegger, Christian', 'Willgert, Katriina J.E.', 'Brisbane-Cohen, Laura', 'Richardson-Lopez, Jill', 'Holmes, Edward C.', 'Parrish, Colin R.']",Emerg Infect Dis,,,False
67a8fef0eb4922c0e41e028b400f11fa88942e04,PMC,US Federal Travel Restrictions for Persons with Higher-Risk Exposures to Communicable Diseases of Public Health Concern,http://dx.doi.org/10.3201/eid2313.170386,PMC5711296,29155659,NO-CC CODE,"Published guidance recommends controlled movement for persons with higher-risk exposures (HREs) to communicable diseases of public health concern; US federal public health travel restrictions (PHTRs) might be implemented to enforce these measures. We describe persons eligible for and placed on PHTRs because of HREs during 2014–2016. There were 160 persons placed on PHTRs: 142 (89%) involved exposure to Ebola virus, 16 (10%) to Lassa fever virus, and 2 (1%) to Middle East respiratory syndrome coronavirus. Most (90%) HREs were related to an epidemic. No persons attempted to travel; all persons had PHTRs lifted after completion of a maximum disease-specific incubation period or a revised exposure risk classification. PHTR enforced controlled movement and removed risk for disease transmission among travelers who had contacts who refused to comply with public health recommendations. PHTRs are mechanisms to mitigate spread of communicable diseases and might be critical in enhancing health security during epidemics.",2017 Dec,"['Vonnahme, Laura A.', 'Jungerman, M. Robynne', 'Gulati, Reena K.', 'Illig, Petra', 'Alvarado-Ramy, Francisco']",Emerg Infect Dis,,,True
6699fa6eb0b4fb603f3baf51add71f7ec29ed2a5,PMC,Establishment of CDC Global Rapid Response Team to Ensure Global Health Security,http://dx.doi.org/10.3201/eid2313.170711,PMC5711298,29155672,NO-CC CODE,"The 2014–2016 Ebola virus disease epidemic in West Africa highlighted challenges faced by the global response to a large public health emergency. Consequently, the US Centers for Disease Control and Prevention established the Global Rapid Response Team (GRRT) to strengthen emergency response capacity to global health threats, thereby ensuring global health security. Dedicated GRRT staff can be rapidly mobilized for extended missions, improving partner coordination and the continuity of response operations. A large, agencywide roster of surge staff enables rapid mobilization of qualified responders with wide-ranging experience and expertise. Team members are offered emergency response training, technical training, foreign language training, and responder readiness support. Recent response missions illustrate the breadth of support the team provides. GRRT serves as a model for other countries and is committed to strengthening emergency response capacity to respond to outbreaks and emergencies worldwide, thereby enhancing global health security.",2017 Dec,"['Stehling-Ariza, Tasha', 'Lefevre, Adrienne', 'Calles, Dinorah', 'Djawe, Kpandja', 'Garfield, Richard', 'Gerber, Michael', 'Ghiselli, Margherita', 'Giese, Coralie', 'Greiner, Ashley L.', 'Hoffman, Adela', 'Miller, Leigh Ann', 'Moorhouse, Lisa', 'Navarro-Colorado, Carlos', 'Walsh, James', 'Bugli, Dante', 'Shahpar, Cyrus']",Emerg Infect Dis,,,True
4fc3b508543068a9d54f11f0ecf52580df768307,PMC,"Global Disease Detection—Achievements in Applied Public Health Research, Capacity Building, and Public Health Diplomacy, 2001–2016",http://dx.doi.org/10.3201/eid2313.170859,PMC5711302,29155662,NO-CC CODE,"The Centers for Disease Control and Prevention has established 10 Global Disease Detection (GDD) Program regional centers around the world that serve as centers of excellence for public health research on emerging and reemerging infectious diseases. The core activities of the GDD Program focus on applied public health research, surveillance, laboratory, public health informatics, and technical capacity building. During 2015–2016, program staff conducted 205 discrete projects on a range of topics, including acute respiratory illnesses, health systems strengthening, infectious diseases at the human–animal interface, and emerging infectious diseases. Projects incorporated multiple core activities, with technical capacity building being most prevalent. Collaborating with host countries to implement such projects promotes public health diplomacy. The GDD Program continues to work with countries to strengthen core capacities so that emerging diseases can be detected and stopped faster and closer to the source, thereby enhancing global health security.",2017 Dec,"['Rao, Carol Y.', 'Goryoka, Grace W.', 'Henao, Olga L.', 'Clarke, Kevin R.', 'Salyer, Stephanie J.', 'Montgomery, Joel M.']",Emerg Infect Dis,,,True
a22d836f2da3eb697e877de9bddcb4785d2e8b1e,PMC,CDC Support for Global Public Health Emergency Management,http://dx.doi.org/10.3201/eid2313.170542,PMC5711305,29155652,NO-CC CODE,"Recent pandemics and rapidly spreading outbreaks of infectious diseases have illustrated the interconnectedness of the world and the importance of improving the international community’s ability to effectively respond. The Centers for Disease Control and Prevention (CDC), building on a strong foundation of lessons learned through previous emergencies, international recognition, and human and technical expertise, has aspired to support nations around the world to strengthen their public health emergency management (PHEM) capacity. PHEM principles streamline coordination and collaboration in responding to infectious disease outbreaks, which align with the core capacities outlined in the International Health Regulations 2005. CDC supports PHEM by providing in-country technical assistance, aiding the development of plans and procedures, and providing fellowship opportunities for public health emergency managers. To this end, CDC partners with US agencies, international partners, and multilateral organizations to support nations around the world to reduce illness and death from outbreaks of infectious diseases.",2017 Dec,"['Brencic, Daniel J.', 'Pinto, Meredith', 'Gill, Adrienne', 'Kinzer, Michael H.', 'Hernandez, Luis', 'Pasi, Omer G.']",Emerg Infect Dis,,,True
866a7c1104e852ef5c06108cf6b9aa3334edc327,PMC,"Prioritizing Zoonoses for Global Health Capacity Building—Themes from One Health Zoonotic Disease Workshops in 7 Countries, 2014–2016",http://dx.doi.org/10.3201/eid2313.170418,PMC5711306,29155664,NO-CC CODE,"Zoonotic diseases represent critical threats to global health security. Effective mitigation of the impact of endemic and emerging zoonotic diseases of public health importance requires multisectoral collaboration and interdisciplinary partnerships. The US Centers for Disease Control and Prevention created the One Health Zoonotic Disease Prioritization Tool to help countries identify zoonotic diseases of greatest national concern using input from representatives of human health, agriculture, environment, and wildlife sectors. We review 7 One Health Zoonotic Disease Prioritization Tool workshops conducted during 2014–2016, highlighting workshop outcomes, lessons learned, and shared themes from countries implementing this process. We also describe the tool’s ability to help countries focus One Health capacity-building efforts to appropriately prevent, detect, and respond to zoonotic disease threats.",2017 Dec,"['Salyer, Stephanie J.', 'Silver, Rachel', 'Simone, Kerri', 'Barton Behravesh, Casey']",Emerg Infect Dis,,,True
3e8f1cce602f86dd1f7227dbfe0c21ac995ff470,PMC,Sustainable Model for Public Health Emergency Operations Centers for Global Settings,http://dx.doi.org/10.3201/eid2313.170435,PMC5711308,29155649,NO-CC CODE,"Capacity to receive, verify, analyze, assess, and investigate public health events is essential for epidemic intelligence. Public health Emergency Operations Centers (PHEOCs) can be epidemic intelligence hubs by 1) having the capacity to receive, analyze, and visualize multiple data streams, including surveillance and 2) maintaining a trained workforce that can analyze and interpret data from real-time emerging events. Such PHEOCs could be physically located within a ministry of health epidemiology, surveillance, or equivalent department rather than exist as a stand-alone space and serve as operational hubs during nonoutbreak times but in emergencies can scale up according to the traditional Incident Command System structure.",2017 Dec,"['Balajee, S. Arunmozhi', 'Pasi, Omer G.', 'Etoundi, Alain Georges M.', 'Rzeszotarski, Peter', 'Do, Trang T.', 'Hennessee, Ian', 'Merali, Sharifa', 'Alroy, Karen A.', 'Phu, Tran Dac', 'Mounts, Anthony W.']",Emerg Infect Dis,,,True
7bf3533ae81b36dc5c59339e5d62eb57065f27cd,PMC,Sustainable Model for Public Health Emergency Operations Centers for Global Settings,http://dx.doi.org/10.3201/eid2313.170435,PMC5711308,29155649,NO-CC CODE,"Capacity to receive, verify, analyze, assess, and investigate public health events is essential for epidemic intelligence. Public health Emergency Operations Centers (PHEOCs) can be epidemic intelligence hubs by 1) having the capacity to receive, analyze, and visualize multiple data streams, including surveillance and 2) maintaining a trained workforce that can analyze and interpret data from real-time emerging events. Such PHEOCs could be physically located within a ministry of health epidemiology, surveillance, or equivalent department rather than exist as a stand-alone space and serve as operational hubs during nonoutbreak times but in emergencies can scale up according to the traditional Incident Command System structure.",2017 Dec,"['Balajee, S. Arunmozhi', 'Pasi, Omer G.', 'Etoundi, Alain Georges M.', 'Rzeszotarski, Peter', 'Do, Trang T.', 'Hennessee, Ian', 'Merali, Sharifa', 'Alroy, Karen A.', 'Phu, Tran Dac', 'Mounts, Anthony W.']",Emerg Infect Dis,,,False
4e5eacfc3bdbbfb287913b6ddf6e3ac1ca39c879,PMC,Global Health Security—An Unfinished Journey,http://dx.doi.org/10.3201/eid2313.171528,PMC5711312,,NO-CC CODE,"This supplement is a timely, comprehensive compendium of the critical work being done by the Centers for Disease Control and Prevention and various partners to enhance and expand the Global Health Security Agenda. This perspective provides a review of, and comments regarding, our past, current, and future challenges in supporting the Global Health Security Agenda.",2017 Dec,"Osterholm, Michael T.",Emerg Infect Dis,,,True
4b5a80aaf5026238a6c6a440bb5b39ba8497c815,PMC,US Centers for Disease Control and Prevention and Its Partners’ Contributions to Global Health Security,http://dx.doi.org/10.3201/eid2313.170946,PMC5711315,29155656,NO-CC CODE,"To achieve compliance with the revised World Health Organization International Health Regulations (IHR 2005), countries must be able to rapidly prevent, detect, and respond to public health threats. Most nations, however, remain unprepared to manage and control complex health emergencies, whether due to natural disasters, emerging infectious disease outbreaks, or the inadvertent or intentional release of highly pathogenic organisms. The US Centers for Disease Control and Prevention (CDC) works with countries and partners to build and strengthen global health security preparedness so they can quickly respond to public health crises. This report highlights selected CDC global health protection platform accomplishments that help mitigate global health threats and build core, cross-cutting capacity to identify and contain disease outbreaks at their source. CDC contributions support country efforts to achieve IHR 2005 compliance, contribute to the international framework for countering infectious disease crises, and enhance health security for Americans and populations around the world.",2017 Dec,"['Tappero, Jordan W.', 'Cassell, Cynthia H.', 'Bunnell, Rebecca E.', 'Angulo, Frederick J.', 'Craig, Allen', 'Pesik, Nicki', 'Dahl, Benjamin A.', 'Ijaz, Kashef', 'Jafari, Hamid', 'Martin, Rebecca', None]",Emerg Infect Dis,,,True
ca7208e80e01498b6aa51efded32283f2827a634,PMC,Zoonotic Disease Programs for Enhancing Global Health Security,http://dx.doi.org/10.3201/eid2313.170544,PMC5711319,29155661,NO-CC CODE,"Most infectious diseases that recently emerged in humans originated in animals. Besides close contact between animals and humans, other factors probably contribute to the cross-species transmission of infectious diseases. It is critical to establish effective mechanisms for coordination and collaboration between the animal, human, and environmental health sectors before new threats emerge by bringing the different sectors together to tackle endemic zoonotic diseases of greatest concern. Such multisectoral partnerships should begin by identifying priority zoonotic diseases for national engagement with equal input from the different sectors. Improvements in surveillance and data sharing for prioritized zoonotic diseases and enhancements of laboratory testing and joint outbreak response capacities in the human and animal health sectors will create and strengthen the mechanisms necessary to effectively detect and respond to emerging health threats, and thereby enhance global health security.",2017 Dec,"['Belay, Ermias D.', 'Kile, James C.', 'Hall, Aron J.', 'Barton-Behravesh, Casey', 'Parsons, Michele B.', 'Salyer, Stephanie', 'Walke, Henry']",Emerg Infect Dis,,,True
d1e4a15d8ddab3043d3727443599a6ab43765bd3,PMC,"Lessons Learned from Emergency Response Vaccination Efforts for Cholera, Typhoid, Yellow Fever, and Ebola",http://dx.doi.org/10.3201/eid2313.170550,PMC5711321,29155670,NO-CC CODE,"Countries must be prepared to respond to public health threats associated with emergencies, such as natural disasters, sociopolitical conflicts, or uncontrolled disease outbreaks. Rapid vaccination of populations vulnerable to epidemic-prone vaccine-preventable diseases is a major component of emergency response. Emergency vaccination planning presents challenges, including how to predict resource needs, expand vaccine availability during global shortages, and address regulatory barriers to deliver new products. The US Centers for Disease Control and Prevention supports countries to plan, implement, and evaluate emergency vaccination response. We describe work of the Centers for Disease Control and Prevention in collaboration with global partners to support emergency vaccination against cholera, typhoid, yellow fever, and Ebola, diseases for which a new vaccine or vaccine formulation has played a major role in response. Lessons learned will help countries prepare for future emergencies. Integration of vaccination with emergency response augments global health security through reducing disease burden, saving lives, and preventing spread across international borders.",2017 Dec,"['Walldorf, Jenny A.', 'Date, Kashmira A.', 'Sreenivasan, Nandini', 'Harris, Jennifer B.', 'Hyde, Terri B.']",Emerg Infect Dis,,,True
e315c421674f55c4e12287ff86314290f8965432,PMC,Enhancing Laboratory Response Network Capacity in South Korea,http://dx.doi.org/10.3201/eid2313.170348,PMC5711322,29155653,NO-CC CODE,"Laboratory Response Network (LRN) laboratories help protect populations from biological and chemical public health threats. We examined the role of LRN biological laboratories in enhancing capacity to detect and respond to public health infectious disease emergencies in South Korea. The model for responding to infectious disease emergencies leverages standardized laboratory testing procedures, a repository of standardized testing reagents, laboratory testing cooperation among hospital sentinel laboratories and reference laboratories, and maintenance of a trained workforce through traditional and on-demand training. Cooperation among all network stakeholders helps ensure that laboratory response is an integrated part of the national response. The added laboratory testing capacity provided by the US Centers for Disease Control and Prevention LRN assets helps protect persons who reside in South Korea, US military personnel and civilians in South Korea, and those who reside in the continental United States.",2017 Dec,"['Parker, J. Todd', 'Juren, Ann-Christian', 'Lowe, Luis', 'Santibañez, Scott', 'Rhie, Gi-eun', 'Merlin, Toby L.']",Emerg Infect Dis,,,True
54f05a81f01710c9f2c441e30233bca6163da6a9,PMC,Joint External Evaluation—Development and Scale-Up of Global Multisectoral Health Capacity Evaluation Process,http://dx.doi.org/10.3201/eid2313.170949,PMC5711324,29155678,NO-CC CODE,"The Joint External Evaluation (JEE), a consolidation of the World Health Organization (WHO) International Health Regulations 2005 (IHR 2005) Monitoring and Evaluation Framework and the Global Health Security Agenda country assessment tool, is an objective, voluntary, independent peer-to-peer multisectoral assessment of a country’s health security preparedness and response capacity across 19 IHR technical areas. WHO approved the standardized JEE tool in February 2016. The JEE process is wholly transparent; countries request a JEE and are encouraged to make its findings public. Donors (e.g., member states, public and private partners, and other public health institutions) can support countries in addressing identified JEE gaps, and implementing country-led national action plans for health security. Through July 2017, 52 JEEs were completed, and 25 more countries were scheduled across WHO’s 6 regions. JEEs facilitate progress toward IHR 2005 implementation, thereby building trust and mutual accountability among countries to detect and respond to public health threats.",2017 Dec,"['Bell, Elizabeth', 'Tappero, Jordan W.', 'Ijaz, Kashef', 'Bartee, Maureen', 'Fernandez, Jose', 'Burris, Hannah', 'Sliter, Karen', 'Nikkari, Simo', 'Chungong, Stella', 'Rodier, Guenael', 'Jafari, Hamid', None]",Emerg Infect Dis,,,True
6198c45ade2c9f644ed7556b30e5736439b7e1b2,PMC,Building Global Epidemiology and Response Capacity with Field Epidemiology Training Programs,http://dx.doi.org/10.3201/eid2313.170509,PMC5711325,29155658,NO-CC CODE,"More than ever, competent field epidemiologists are needed worldwide. As known, new, and resurgent communicable diseases increase their global impact, the International Health Regulations and the Global Health Security Agenda call for sufficient field epidemiologic capacity in every country to rapidly detect, respond to, and contain public health emergencies, thereby ensuring global health security. To build this capacity, for >35 years the US Centers for Disease Control and Prevention has worked with countries around the globe to develop Field Epidemiology Training Programs (FETPs). FETP trainees conduct surveillance activities and outbreak investigations in service to ministry of health programs to prevent and control infectious diseases of global health importance such as polio, cholera, tuberculosis, HIV/AIDS, malaria, and emerging zoonotic infectious diseases. FETP graduates often rise to positions of leadership to direct such programs. By training competent epidemiologists to manage public health events locally and support public health systems nationally, health security is enhanced globally.",2017 Dec,"['Jones, Donna S.', 'Dicker, Richard C.', 'Fontaine, Robert E.', 'Boore, Amy L.', 'Omolo, Jared O.', 'Ashgar, Rana J.', 'Baggett, Henry C.']",Emerg Infect Dis,,,True
2140635bd0abbea93a3dbb83af50aff3485b6b8c,PMC,Contributions of the US Centers for Disease Control and Prevention in Implementing the Global Health Security Agenda in 17 Partner Countries,http://dx.doi.org/10.3201/eid2313.170898,PMC5711326,29155676,NO-CC CODE,"The Global Health Security Agenda (GHSA), a partnership of nations, international organizations, and civil society, was launched in 2014 with a mission to build countries’ capacities to respond to infectious disease threats and to foster global compliance with the International Health Regulations (IHR 2005). The US Centers for Disease Control and Prevention (CDC) assists partner nations to improve IHR 2005 capacities and achieve GHSA targets. To assess progress through these CDC-supported efforts, we analyzed country activity reports dating from April 2015 through March 2017. Our analysis shows that CDC helped 17 Phase I countries achieve 675 major GHSA accomplishments, particularly in the cross-cutting areas of public health surveillance, laboratory systems, workforce development, and emergency response management. CDC’s engagement has been critical to these accomplishments, but sustained support is needed until countries attain IHR 2005 capacities, thereby fostering national and regional health protection and ensuring a world safer and more secure from global health threats.",2017 Dec,"['Fitzmaurice, Arthur G.', 'Mahar, Michael', 'Moriarty, Leah F.', 'Bartee, Maureen', 'Hirai, Mitsuaki', 'Li, Wenshu', 'Gerber, A. Russell', 'Tappero, Jordan W.', 'Bunnell, Rebecca', None]",Emerg Infect Dis,,,True
31fae2807695521804442fedcd3f7b9f17d0f9ea,PMC,Characterization of Variability in Toxicokinetics and Toxicodynamics of Tetrachloroethylene Using the Collaborative Cross Mouse Population,http://dx.doi.org/10.1289/EHP788,PMC5726344,28572074,NO-CC CODE,"BACKGROUND: Evaluation of interindividual variability is a challenging step in risk assessment. For most environmental pollutants, including perchloroethylene (PERC), experimental data are lacking, resulting in default assumptions being used to account for variability in toxicokinetics and toxicodynamics. OBJECTIVE: We quantitatively examined the relationship between PERC toxicokinetics and toxicodynamics at the population level to test whether individuals with increased oxidative metabolism are be more sensitive to hepatotoxicity following PERC exposure. METHODS: Male mice from 45 strains of the Collaborative Cross (CC) were orally administered a single dose of PERC ([Formula: see text]) or vehicle (Alkamuls-EL620) and euthanized at various time points ([Formula: see text] /strain/time). Concentration–time profiles were generated for PERC and its primary oxidative metabolite trichloroacetate (TCA) in multiple tissues. Toxicodynamic phenotyping was also performed. RESULTS: Significant variability among strains was observed in toxicokinetics of PERC and TCA in every tissue examined. Based on area under the curve (AUC), the range of liver TCA levels spanned nearly an order of magnitude ([Formula: see text]-fold). Expression of liver cytochrome P4502E1 did not correlate with TCA levels. Toxicodynamic phenotyping revealed an effect of PERC on bodyweight loss, induction of peroxisome proliferator activated receptor-alpha (PPAR [Formula: see text])-regulated genes, and dysregulation of hepatic lipid homeostasis. Clustering was observed among a) liver levels of PERC, TCA, and triglycerides; b) TCA levels in liver and kidney; and c) TCA levels in serum, brain, fat, and lung. CONCLUSIONS: Using the CC mouse population model, we have demonstrated a complex and highly variable relationship between PERC and TCA toxicokinetics and toxicodynamics at the population level. https://doi.org/10.1289/EHP788",2017 May 30,"['Cichocki, Joseph A.', 'Furuya, Shinji', 'Venkatratnam, Abhishek', 'McDonald, Thomas J.', 'Knap, Anthony H.', 'Wade, Terry', 'Sweet, Stephen', 'Chiu, Weihsueh A.', 'Threadgill, David W.', 'Rusyn, Ivan']",Environ Health Perspect,,,True
476cc169df365bb43b3d4763845b8b8234916cb3,PMC,Characterization of Variability in Toxicokinetics and Toxicodynamics of Tetrachloroethylene Using the Collaborative Cross Mouse Population,http://dx.doi.org/10.1289/EHP788,PMC5726344,28572074,NO-CC CODE,"BACKGROUND: Evaluation of interindividual variability is a challenging step in risk assessment. For most environmental pollutants, including perchloroethylene (PERC), experimental data are lacking, resulting in default assumptions being used to account for variability in toxicokinetics and toxicodynamics. OBJECTIVE: We quantitatively examined the relationship between PERC toxicokinetics and toxicodynamics at the population level to test whether individuals with increased oxidative metabolism are be more sensitive to hepatotoxicity following PERC exposure. METHODS: Male mice from 45 strains of the Collaborative Cross (CC) were orally administered a single dose of PERC ([Formula: see text]) or vehicle (Alkamuls-EL620) and euthanized at various time points ([Formula: see text] /strain/time). Concentration–time profiles were generated for PERC and its primary oxidative metabolite trichloroacetate (TCA) in multiple tissues. Toxicodynamic phenotyping was also performed. RESULTS: Significant variability among strains was observed in toxicokinetics of PERC and TCA in every tissue examined. Based on area under the curve (AUC), the range of liver TCA levels spanned nearly an order of magnitude ([Formula: see text]-fold). Expression of liver cytochrome P4502E1 did not correlate with TCA levels. Toxicodynamic phenotyping revealed an effect of PERC on bodyweight loss, induction of peroxisome proliferator activated receptor-alpha (PPAR [Formula: see text])-regulated genes, and dysregulation of hepatic lipid homeostasis. Clustering was observed among a) liver levels of PERC, TCA, and triglycerides; b) TCA levels in liver and kidney; and c) TCA levels in serum, brain, fat, and lung. CONCLUSIONS: Using the CC mouse population model, we have demonstrated a complex and highly variable relationship between PERC and TCA toxicokinetics and toxicodynamics at the population level. https://doi.org/10.1289/EHP788",2017 May 30,"['Cichocki, Joseph A.', 'Furuya, Shinji', 'Venkatratnam, Abhishek', 'McDonald, Thomas J.', 'Knap, Anthony H.', 'Wade, Terry', 'Sweet, Stephen', 'Chiu, Weihsueh A.', 'Threadgill, David W.', 'Rusyn, Ivan']",Environ Health Perspect,,,False
d6a8375529a761648f605f507786e218d0bd558a,PMC,"DETECTION OF CANINE PARVOVIRUS ANTIGEN IN DOGS IN KUMASI, GHANA",http://dx.doi.org/10.21010/ajid.v12i1.5,PMC5733252,29302647,NO-CC CODE,"BACKGROUND: Canine Parvovirus (CPV) in dogs has been documented in many countries. However, evidence of the infection is scanty in Ghana. This study was conducted to detect canine parvovirus antigen in dogs presented with diarrhoea to the Government Veterinary Clinic in Kumasi, Ghana. MATERIALS AND METHODS: Faecal samples from 72 dogs presented with diarrhoea were tested for the presence of canine parvovirus antigen using commercially available rapid test kit (BIT(®) Rapid Colour Canine Parvovirus Ag Test Kit, BIOINDIST Co. Ltd, Korea) based on the principle of immunochromatography. Influence of breed, sex, age, vaccination history and the nature of diarrhoea were assessed. Data obtained was analysed with SPSS and subjected to the chi-square test. Significance was at α(0.05) RESULTS: We found 61.11% tested positive (44/72) for CPV. Based on sex, 61.54% of males (20/33) and 60.61% of females tested positive (24/39). A total of 65.67% of samples from puppies below 6 months were positive. 56.25% of CPV vaccinated dogs and 70.83% of unvaccinated dogs were positive respectively. 69.05% of samples from haemorrhagic diarrhoeic dogs and 50.00% from non-haemorrhagic diarrhoeic dogs were positive of CPV. CONCLUSION: The study is the first documented evidence of the existence of CPV in Ghana. It also revealed that absence of bloody diarrhoea does not necessarily rule out CPV infection.",2017 Nov 15,"['Folitse, R. D', 'Kodie, D.O', 'Amemor, E.', 'Dei, D.', 'Tasiame, W.', 'Burimuah, V.', 'Emikpe, B.O']",Afr J Infect Dis,,,True
170447c8d130a81bb16cd4232cb1332bcc8a1863,PMC,Lipoquality control by phospholipase A(2) enzymes,http://dx.doi.org/10.2183/pjab.93.043,PMC5743847,29129849,NO-CC CODE,"The phospholipase A(2) (PLA(2)) family comprises a group of lipolytic enzymes that typically hydrolyze the sn-2 position of glycerophospholipids to give rise to fatty acids and lysophospholipids. The mammalian genome encodes more than 50 PLA(2)s or related enzymes, which are classified into several subfamilies on the basis of their structures and functions. From a general viewpoint, the PLA(2) family has mainly been implicated in signal transduction, producing bioactive lipid mediators derived from fatty acids and lysophospholipids. Recent evidence indicates that PLA(2)s also contribute to phospholipid remodeling for membrane homeostasis or energy production for fatty acid β-oxidation. Accordingly, PLA(2) enzymes can be regarded as one of the key regulators of the quality of lipids, which I herein refer to as lipoquality. Disturbance of PLA(2)-regulated lipoquality hampers tissue and cellular homeostasis and can be linked to various diseases. Here I overview the current state of understanding of the classification, enzymatic properties, and physiological functions of the PLA(2) family.",2017 Nov 10,"MURAKAMI, Makoto",Proc Jpn Acad Ser B Phys Biol Sci,,,True
ed838e94ba83d3f0d4f435adc3ded47219534b2d,PMC,Deadliest Enemy: Our War against Killer Germs,http://dx.doi.org/10.3201/eid2401.171081,PMC5749459,,NO-CC CODE,,2018 Jan,"Adalja, Amesh A.",Emerg Infect Dis,,,False
da692ee969d9c33986196372c3f7cb87fa6b6f8f,PMC,Database resources of the National Center for Biotechnology Information,http://dx.doi.org/10.1093/nar/gkx1095,PMC5753372,29140470,NO-CC CODE,"The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank(®) nucleic acid sequence database and the PubMed database of citations and abstracts for published life science journals. The Entrez system provides search and retrieval operations for most of these data from 39 distinct databases. The E-utilities serve as the programming interface for the Entrez system. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. New resources released in the past year include PubMed Data Management, RefSeq Functional Elements, genome data download, variation services API, Magic-BLAST, QuickBLASTp, and Identical Protein Groups. Resources that were updated in the past year include the genome data viewer, a human genome resources page, Gene, virus variation, OSIRIS, and PubChem. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.",2018 Jan 4,,Nucleic Acids Res,,,True
46f3939764340a0e8274772f0cda101e7e4cb361,PMC,An early report from newly established laboratory‐based influenza surveillance in Lao PDR,http://dx.doi.org/10.1111/j.1750-2659.2009.00120.x,PMC5779283,20167044,NO-CC CODE,"Please cite this paper as: Vongphrachanh P, Simmerman JM, Phonekeo D, Pansayavong V, Sisouk T, Ongkhamme S, Bryce GT, Corwin A, Bryant JE. An early report from newly established laboratory‐based influenza surveillance in Lao PDR. Influenza and Other Respiratory Viruses 4(2), 47–52. Background  Prior to 2007, little information was available about the burden of influenza in Laos. We report data from the first laboratory‐based influenza surveillance system established in the Lao People’s Democratic Republic. Methods  Three hospitals in the capital city of Vientiane began surveillance for influenza‐like illness (ILI) in outpatients in 2007 and expanded to include hospitalized pneumonia patients in 2008. Nasal/throat swab specimens were collected and tested for influenza and other respiratory viruses by multiplex ID‐Tag(TM) respiratory viral panel (RVP) assay on a Luminex® 100× MAP IS instrument (Qiagen, Singapore). Results  During January 2007 to December 2008, 287 of 526 (54·6%) outpatients with ILI were positive for at least one respiratory virus. Influenza was most commonly identified, with 63 (12·0%) influenza A and 92 (17·5%) influenza B positive patients identified. In 2008, six of 79 (7·6%) hospitalized pneumonia patients were positive for influenza A and four (5·1%) were positive for influenza B. Children <5 years represented 19% of viral infections in outpatients and 38% of pneumonia inpatients. Conclusion  Our results provide the first documentation of influenza burden among patients with febrile respiratory illness and pneumonia requiring hospitalization in Laos. Implementing laboratory‐based influenza surveillance requires substantial investments in infrastructure and training. However, continuing outbreaks of avian influenza A/H5N1 in poultry and emergence of the 2009 influenza A(H1N1) pandemic strain further underscore the importance of establishing and maintaining influenza surveillance in developing countries.",2010 Mar 4,"['Vongphrachanh, Phengta', 'Simmerman, James M.', 'Phonekeo, Darouny', 'Pansayavong, Vimatha', 'Sisouk, Thongchanh', 'Ongkhamme, Somvay', 'Bryce, Gary T.', 'Corwin, Andrew', 'Bryant, Juliet E.']",Influenza Other Respir Viruses,,,True
e9ac8478a11cfde0b9a1b860613104da3d47021b,PMC,Erratum,,PMC5779384,,NO-CC CODE,,2014 Jun 27,,MMWR Morb Mortal Wkly Rep,,,False
5d9e264d5bedc5753d9feede10389f71b08e0446,PMC,"Assessment of Potential Zoonotic Disease Exposure and Illness Related to an Annual Bat Festival — Idanre, Nigeria",,PMC5779396,24739343,NO-CC CODE,,2014 Apr 18,"['Vora, Neil M.', 'Osinubi, Modupe', 'Wallace, Ryan M.', 'Aman-Oloniyo, Abimbola', 'Gbadegesin, Yemi H.', 'Sebastian, Yennan Kerecvel', 'Saliman, Olugbon Abdullateef', 'Niezgoda, Mike', 'Davis, Lora', 'Recuenco, Sergio']",MMWR Morb Mortal Wkly Rep,,,True
1c55b6759fc6303eedae05d52530ced11c30a6d6,PMC,"First Confirmed Cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection in the United States, Updated Information on the Epidemiology of MERS-CoV Infection, and Guidance for the Public, Clinicians, and Public Health Authorities — May 2014",,PMC5779407,24827411,NO-CC CODE,,2014 May 16,"['Bialek, Stephanie R.', 'Allen, Donna', 'Alvarado-Ramy, Francisco', 'Arthur, Ray', 'Balajee, Arunmozhi', 'Bell, David', 'Best, Susan', 'Blackmore, Carina', 'Breakwell, Lucy', 'Cannons, Andrew', 'Brown, Clive', 'Cetron, Martin', 'Chea, Nora', 'Chommanard, Christina', 'Cohen, Nicole', 'Conover, Craig', 'Crespo, Antonio', 'Creviston, Jeanean', 'Curns, Aaron T.', 'Dahl, Rebecca', 'Dearth, Stephanie', 'DeMaria, Alfred', 'Echols, Fred', 'Erdman, Dean D.', 'Feikin, Daniel', 'Frias, Mabel', 'Gerber, Susan I.', 'Gulati, Reena', 'Hale, Christa', 'Haynes, Lia M.', 'Heberlein-Larson, Lea', 'Holton, Kelly', 'Ijaz, Kashef', 'Kapoor, Minal', 'Kohl, Katrin', 'Kuhar, David T.', 'Kumar, Alan M.', 'Kundich, Marianne', 'Lippold, Susan', 'Liu, Lixia', 'Lovchik, Judith C.', 'Madoff, Larry', 'Martell, Sandra', 'Matthews, Sarah', 'Moore, Jessica', 'Murray, Linda R.', 'Onofrey, Shauna', 'Pallansch, Mark A.', 'Pesik, Nicki', 'Pham, Huong', 'Pillai, Satish', 'Pontones, Pam', 'Poser, Sarah', 'Pringle, Kimberly', 'Pritchard, Scott', 'Rasmussen, Sonja', 'Richards, Shawn', 'Sandoval, Michelle', 'Schneider, Eileen', 'Schuchat, Anne', 'Sheedy, Kristine', 'Sherin, Kevin', 'Swerdlow, David L.', 'Tappero, Jordan W.', 'Vernon, Michael O.', 'Watkins, Sharon', 'Watson, John']",MMWR Morb Mortal Wkly Rep,,,True
bd04b79a0dba1a6f912d0ee7604ab62f84b6734c,PMC,"World Pneumonia Day — November 12, 2014",,PMC5779488,,NO-CC CODE,,2014 Nov 7,,MMWR Morb Mortal Wkly Rep,,,True
963dfcc10563ef66cf366f73640ab9b3e84a9a55,PMC,The use of masks and respirators to prevent transmission of influenza: a systematic review of the scientific evidence,http://dx.doi.org/10.1111/j.1750-2659.2011.00307.x,PMC5779801,22188875,NO-CC CODE,"Please cite this paper as: bin‐Reza et al. (2012) The use of masks and respirators to prevent transmission of influenza: a systematic review of the scientific evidence. Influenza and Other Respiratory Viruses 6(4), 257–267. There are limited data on the use of masks and respirators to reduce transmission of influenza. A systematic review was undertaken to help inform pandemic influenza guidance in the United Kingdom. The initial review was performed in November 2009 and updated in June 2010 and January 2011. Inclusion criteria included randomised controlled trials and quasi‐experimental and observational studies of humans published in English with an outcome of laboratory‐confirmed or clinically‐diagnosed influenza and other viral respiratory infections. There were 17 eligible studies. Six of eight randomised controlled trials found no significant differences between control and intervention groups (masks with or without hand hygiene; N95/P2 respirators). One household trial found that mask wearing coupled with hand sanitiser use reduced secondary transmission of upper respiratory infection/influenza‐like illness/laboratory‐confirmed influenza compared with education; hand sanitiser alone resulted in no reduction. One hospital‐based trial found a lower rate of clinical respiratory illness associated with non‐fit‐tested N95 respirator use compared with medical masks. Eight of nine retrospective observational studies found that mask and/or respirator use was independently associated with a reduced risk of severe acute respiratory syndrome (SARS). Findings, however, may not be applicable to influenza and many studies were suboptimal. None of the studies established a conclusive relationship between mask/respirator use and protection against influenza infection. Some evidence suggests that mask use is best undertaken as part of a package of personal protection especially hand hygiene. The effectiveness of masks and respirators is likely linked to early, consistent and correct usage.",2012 Jul 21,"['bin‐Reza, Faisal', 'Lopez Chavarrias, Vicente', 'Nicoll, Angus', 'Chamberland, Mary E.']",Influenza Other Respir Viruses,,,True
817b21573c7e32c6012a2bc7d34c013ebfdc46f9,PMC,"Invasive bacterial infections following influenza: a time‐series analysis in Montréal, Canada, 1996–2008",http://dx.doi.org/10.1111/j.1750-2659.2011.00297.x,PMC5779805,21985083,NO-CC CODE,"Please cite this paper as: Allard et al. (2012) Invasive bacterial infections following influenza: a time‐series analysis in Montréal, Canada, 1996–2008. Influenza and Other Respiratory Viruses 6(4), 268–275. Background  Shared seasonal patterns, such as between influenza and some respiratory bacterial infections, can create associations between phenomena not causally related. Objectives  To estimate the association of influenza with subsequent bacterial infections after full adjustment for confounding by seasonal and long‐term trends. Methods  Time series of weekly counts of notified cases of invasive infections with Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae and Streptococcus pyogenes, in Montréal, Canada, 1996–2008, were modelled by negative binomial regression, with terms representing seasonal and long‐term trends and terms for numbers of positive laboratory tests for influenza A and B. Results  The associations of S. pneumoniae, H. influenzae and N. meningitidis with influenza disappeared after seasonal terms were added to the model. However, the influenza B count remained associated with the S. pyogenes counts for the same week and the following week: S. pyogenes incidence rate ratios were 1.0376 (95% CI: 1.0009–1.0757) and 1.0354 (0.9958–1.0766), respectively, for each increase of 1 in the influenza count. Conclusions  Influenza B accounts for about 8percnt; of the incidence of invasive S. pyogenes infections, over and above any effect associated with modellable seasonal and long‐term trends. This association of influenza B with S. pyogenes infections can be attributed largely to the years 1997, 2001, 2007 and 2008, when late peaks in influenza B counts were followed by peaks in S. pyogenes notifications. This finding reinforces the case for universal immunization against influenza, as partial protection against the ‘flesh eating disease’.",2012 Jul 10,"['Allard, R.', 'Couillard, M.', 'Pilon, P.', 'Kafka, M.', 'Bédard, L.']",Influenza Other Respir Viruses,,,True
23429be08d135da1c9786b2347f0a6ec92653695,PMC,Pandemic positives – a seroepidemiology consortium has formed and significant A(H1N1)pdm09 research continues to flow and demand journal pages,http://dx.doi.org/10.1111/irv.12114,PMC5779830,23594213,NO-CC CODE,,2013 May 17,"Hampson, Alan W.",Influenza Other Respir Viruses,,,False
a23739aba0ae99bdf7e687731f4c61770cb6569d,PMC,Virus detection and its association with symptoms during influenza‐like illness in a sample of healthy adults enrolled in a randomised controlled vaccine trial,http://dx.doi.org/10.1111/j.1750-2659.2012.00395.x,PMC5779839,22712831,NO-CC CODE,"Background  Viral respiratory infections are associated with significant morbidity and mortality. Many new aetiological agents have been described recently. Objectives  We looked for respiratory viruses in a population‐based sample of healthy adults with influenza‐like illness (ILI). We investigated host and spatio‐temporal associations with virus isolation and host, spatio‐temporal and virus associations with self‐reported symptoms. Patients/Methods  We recruited 586 participants experiencing 651 illness episodes from a population of healthy adults enrolled in an influenza vaccine effectiveness trial. At ILI assessment visits, a respiratory swab was collected and tested for viruses using a combination of polymerase chain reaction (PCR) assays. Participants also completed a questionnaire detailing their clinical course in 336 episodes. Results  Of 643 samples analysed, a virus was identified in 44%. Half were picornaviruses, with influenza and coronaviruses the next most common. Individuals with influenza were significantly less likely to have been immunised than the reference (virus negative) population (OR = 0·52 (0·31, 0·87) P = 0·01). The mean symptom score (95% CI) reported by individuals with influenza was significantly higher than in all other episodes [Influenza: 10·2 (9·4, 10·9); Other: 7·4 (7·2, 7·7); Difference (95% CI): 2·5 (1·5, 3·5); P < 0·001]. In an analysis restricted to influenza‐positive cases, the symptom score was not attenuated by vaccination. Conclusions  Our findings indicate that a greater number of symptoms are displayed by individuals presenting with influenza confirmed ILI compared with other agents that cause ILI. While influenza vaccination reduced the probability of influenza virus detection, symptom score for influenza‐positive ILI was not attenuated.",2013 May 19,"['Howard, Peter F.', 'McCaw, James M.', 'Richmond, Peter C.', 'Nissen, Michael', 'Sloots, Theo', 'Lambert, Stephen B.', 'Lai, Michael', 'Greenberg, Michael', 'Nolan, Terry', 'McVernon, Jodie']",Influenza Other Respir Viruses,,,True
d349613c2d95360358af0b2c3d576e9ad21dd0c5,PMC,Hospitalization due to human parainfluenza virus–associated lower respiratory tract illness in rural Thailand,http://dx.doi.org/10.1111/j.1750-2659.2012.00393.x,PMC5779843,22716273,NO-CC CODE,"Background  Human parainfluenza viruses (HPIVs) are an important cause of acute respiratory illness in young children but little is known about their epidemiology in the tropics. Methods  From 2003–2007, we conducted surveillance for hospitalized respiratory illness in rural Thailand. We performed reverse‐transcriptase polymerase chain reaction on nasopharyngeal specimens and enzyme immunoassay on paired sera Results  Of 10,097 patients enrolled, 573 (5%) of all ages and 370 (9%) of children <5 years of age had evidence of HPIV infection (HPIV1=189, HPIV2=54, HPIV3=305, untyped=27). Average adjusted annual incidence of HPIV‐associated hospitalized respiratory illness was greatest in children aged <1 year (485 per 100,000 person years). Conclusions  In Thailand, HPIV caused substantial illnesses requiring hospitalization in young children.",2013 May 21,"['Morgan, Oliver W.', 'Chittaganpitch, Malinee', 'Clague, Birgit', 'Chantra, Somrak', 'Sanasuttipun, Wichai', 'Prapasiri, Prabda', 'Naorat, Sathapana', 'Laosirithavorn, Yongjua', 'Peret, Teresa C. T.', 'Erdman, Dean D.', 'Baggett, Henry C.', 'Olsen, Sonja J.', 'Fry, Alicia M.']",Influenza Other Respir Viruses,,,True
38f8dd5509748038aea9b4b7a8a2a39d3edee225,PMC,"Sentinel surveillance for influenza and other respiratory viruses in Côte d’Ivoire, 2003–2010",http://dx.doi.org/10.1111/j.1750-2659.2012.00389.x,PMC5779848,22863403,NO-CC CODE,"Background  Many countries in Africa have lacked sentinel surveillance systems for influenza and are under‐represented in data used for global vaccine strain selection. Objectives  We describe 8 years of sentinel surveillance data and the contribution of influenza and other viruses to medically attended influenza‐like illness (ILI) in Côte d’Ivoire. Methods  Sentinel surveillance was established in 2003. Nasopharyngeal (NP) specimens and epidemiologic data are collected from persons of all ages presenting with ILI at sentinel sites. Respiratory specimens have been tested for influenza using various viral and molecular diagnostic methods. A subset of 470 specimens collected from children aged 0–5 years were tested for multiple respiratory viruses using RT‐PCR. Results  From 2003 to 2010, 5074 NP specimens were collected from patients with ILI. Overall, 969/5074 (19%) of these specimens tested positive for influenza. Seasonal influenza A(H1N1) viruses predominated during 5 years and influenza A(H3N2) viruses predominated during 3 years. Influenza B viruses cocirculated with influenza A viruses during each year from 2004 to 2010. Seasonal peaks in influenza circulation were observed during the months of May, June, and October, with the largest peak corresponding with the primary rainfall season. Of 470 specimens collected from children under aged 5 who were tested for multiple respiratory viruses, a viral respiratory pathogen was detected in 401/470 (85%) of specimens. Commonly detected viruses were RSV (113 of 470 specimens, 24%), rhinoviruses (85/470, 18%), influenza (77/470, 16%), and parainfluenza (75/470, 16%). Conclusion  In Côte d’Ivoire, there is a significant annual contribution of influenza and other respiratory viruses to medically attended ILI.",2013 May 2,"['Kadjo, Hervé A.', 'Ekaza, Euloge', 'Coulibaly, Daouda', 'Kouassi, Damus P.', 'Nzussouo, Ndahwouh T.', 'Kouakou, Bertin', 'Ouattara, Abdoulaye', 'Adjogoua, Edgard V.', 'Akoua–Koffi, Chantal G.', 'Elia, Gilbernair A.', 'Victoir, Kathleen', 'Bretin‐Dosso, Mireille C.', 'Mott, Joshua A.']",Influenza Other Respir Viruses,,,True
eac877909f4f306c9a7e1c2609fb5d73a6b8ba69,PMC,Pediatric non‐influenza respiratory viruses during pandemic influenza,http://dx.doi.org/10.1111/j.1750-2659.2011.00247.x,PMC5780651,21668679,NO-CC CODE,,2011 Nov 13,"['Akçakaya, Necla', 'Kılıç, Ömer', 'Camcıoğlu, Yildiz', 'Çokuğraş, Haluk', 'Midilli, Kenan']",Influenza Other Respir Viruses,,,True
9741eab85f5510655de379d9e3c11f5bf0d2d560,PMC,Role of procalcitonin and C‐reactive protein in differentiation of mixed bacterial infection from 2009 H1N1 viral pneumonia,http://dx.doi.org/10.1111/j.1750-2659.2011.00244.x,PMC5780656,21668682,NO-CC CODE,"Please cite this paper as: Ahn et al. (2011) Role of procalcitonin and C‐reactive protein in differentiation of mixed bacterial infection from 2009 H1N1 viral pneumonia. Influenza and Other Respiratory Viruses 5(6), 398–403. Background  Mixed bacterial infection is an important contributor to morbidity and mortality during influenza pandemics. We evaluated procalcitonin (PCT) and C‐reactive protein (CRP) in differentiating pneumonia caused by mixed bacterial and 2009 H1N1 influenza infection from 2009 H1N1 influenza infection alone. Methods  Data were collected retrospectively over a 7‐month period during the 2009 H1N1 influenza pandemic. Patients visiting emergency department and diagnosed as community‐acquired pneumonia caused by 2009 H1N1 infection were included (n = 60). Results  Mixed bacterial and viral infection pneumonia (n = 16) had significantly higher PCT and CRP levels than pneumonia caused by 2009 H1N1 influenza alone (n = 44, P = 0·019, 0·022 respectively). The sensitivity and specificity for detection of mixed bacterial infection pneumonia was 56% and 84% for PCT > 1·5 ng/ml, and 69% and 63% for CRP > 10 mg/dl. Using PCT and CRP in combination, the sensitivity and specificity were 50% and 93%, respectively. Conclusion  Procalcitonin and CRP alone and their combination had a moderate ability to detect pneumonia of mixed bacterial infection during the 2009 H1N1 pandemic. Considering high specificity, combination of low CRP and PCT result may suggest that pneumonia is unlikely to be caused by mixed bacterial infection.",2011 Nov 30,"['Ahn, Shin', 'Kim, Won Young', 'Kim, Sung‐Han', 'Hong, SangBum', 'Lim, Chae‐Man', 'Koh, YounSuck', 'Lim, Kyung Soo', 'Kim, Won']",Influenza Other Respir Viruses,,,True
54a31f217ac499b477dd23edb24e41e736d906c0,PMC,Respiratory illnesses in Canadian health care workers: a pilot study of influenza vaccine and oseltamivir prophylaxis during the 2007/2008 influenza season,http://dx.doi.org/10.1111/j.1750-2659.2011.00245.x,PMC5780657,21668681,NO-CC CODE,"Please cite this paper as: Coleman et al. (2011) Respiratory illnesses in Canadian health care workers: a pilot study of influenza vaccine and oseltamivir prophylaxis during the 2007/2008 influenza season. Influenza and Other Respiratory Viruses 5(6), 404–408. Background  Data regarding both rates of acute respiratory illness in health care workers and experience with long‐term antiviral prophylaxis are sparse. Objective  To determine the efficacy and tolerability of oseltamivir prophylaxis versus seasonal influenza vaccine for the prevention of influenza among health care workers. Methods  We conducted a pilot, randomized control study during the 2007/2008 influenza season in a tertiary care setting. Adult health care workers 18–69 years of age were recruited and randomly assigned in a 4:1 ratio to receive either oseltamivir (Tamiflu(®); Roche) 75 mg once daily prophylaxis or seasonal influenza (Fluviral(®)) vaccine. Results  Of 56 adults enrolled, 12 received vaccine and 44 received prophylaxis. Incidence of symptomatic laboratory‐confirmed influenza was similar for participants in the vaccine and prophylaxis arms (17% and 24%, respectively; P = 0·71). Participants who developed an acute respiratory illness during the study period reported working 85% of scheduled work days, and 29% stated that they worked despite feeling miserable because they were too busy to stay home. Of 42 participants who initiated oseltamivir prophylaxis, four discontinued it owing to side effects. Median duration of oseltamivir prophylaxis was 121 days, with 34 (81%) continuing ≥12 weeks. Conclusions  During an extended season of suboptimal vaccine match, 22% of health care workers receiving antiviral prophylaxis or seasonal influenza vaccine developed symptomatic laboratory‐confirmed influenza. Long‐term antiviral prophylaxis against influenza was generally well tolerated with good compliance.",2011 Nov 5,"['Coleman, Brenda L.', 'Boggild, Andrea K.', 'Drews, Steven J.', 'Li, Yan', 'Low, Donald E.', 'McGeer, Allison J.']",Influenza Other Respir Viruses,,,True
ba581dc8851307204bba0a4d63c9e1bf10ff6e26,PMC,"Report of the ‘Mechanisms of lung injury and immunomodulator interventions in influenza’ workshop, 21 March 2010, Ventura, California, USA",http://dx.doi.org/10.1111/j.1750-2659.2011.00278.x,PMC5780662,21848616,NO-CC CODE,"Please cite this paper as: Howard et al. (2011) Report of the ‘Mechanisms of lung injury and immunomodulator interventions in influenza’ workshop, 21 March 2010, Ventura, California, USA*. Influenza and Other Respiratory Viruses 5(6), 453–e475. The clinical course of influenza and the extent of lung injury are determined by both viral and host factors, as well as sometimes secondary bacterial infections and exacerbations of underlying conditions. The balance between viral replication and the host immune responses is central to disease pathogenesis, and the extent of lung injury in severe influenza infections may be due in part to overly exuberant or dysregulated innate inflammatory responses or sometimes deficient responses. Acute respiratory distress syndrome (ARDS) is the principal cause of respiratory failure associated with severe influenza. ARDS can be triggered by both direct lung insults (e.g. respiratory pathogens) and systemic insults (e.g. sepsis), and the lung damage is exacerbated by the inflammatory response associated with either infectious or non‐infectious insults. This workshop aimed to review the current understanding of lung injury in acute influenza and describe cellular and molecular mechanisms of lung injury that are common to influenza and infections by other respiratory pathogens. In addition, therapeutic agents that target host response proteins and pathways were identified and investigational agents in development reviewed. A logical strategy would be to combine antiviral treatment with drugs that modify excessive host responses or supplement deficient ones. However, a better understanding of common cell signalling pathways associated with acute lung injury caused by influenza and other pathogens is necessary to understand immunopathologic causes of lung injury. This will help determine which immunomodulatory interventions might be useful, and to predict the appropriate timing and consequences of their use.",2011 Nov 17,"['Howard, Wendy A.', 'Peiris, Malik', 'Hayden, Frederick G.']",Influenza Other Respir Viruses,,,True
04f9e08f4eb5091105c2cca3133719d1bd10b1dc,PMC,Attempted early detection of influenza A (H1N1) pandemic with surveillance data of influenza‐like illness and unexplained pneumonia,http://dx.doi.org/10.1111/j.1750-2659.2011.00248.x,PMC5780665,21668678,NO-CC CODE,"Please cite this paper as: Qian et al. (2011) Attempted early detection of influenza A (H1N1) pandemic with surveillance data of influenza‐like illness and unexplained pneumonia. Influenza and Other Respiratory Viruses 5(6), e479–e486. Background  To collect disease information and provide data for early detection of epidemics, two surveillance systems were established for influenza‐like illness (ILI) and unexplained pneumonia (UP) in Wuxi, People’s Republic of China. Objectives  The current study aims to describe the performance of these surveillance systems during 2004–2009 and to evaluate the value of surveillance data in detection of influenza epidemics. Methods  Two national ILI sentinel hospitals and three UP sentinel hospitals provided data to the surveillance systems. The surveillance data from hospital‐based outpatient clinics and emergency rooms were compared by year. The ILI data of 2009 were further modeled based on previous data using both a control chart method and a moving average regression method. Alarms of potential epidemics would be raised when the input surveillance data surpassed a threshold. Results  In 2009, the proportions of ILI and respiratory illness with fever (one surveillance syndrome of the UP system) to total patient visits (3·40% and 11·76%, respectively) were higher than the previous years. The surveillance data of both systems also showed developing trends similar to the influenza A (H1N1) pandemic in 2009. When the surveillance data of 2009 were fitted in the two detection models, alarms were produced on the occurrence of the first local case of influenza A (H1N1), outbreaks in schools and in general populations. Conclusions  The results indicated the potential for using ILI and UP surveillance data as syndromic indicators to detect and provide an early warning for influenza epidemics.",2011 Nov 18,"['Qian, Yan‐Hua', 'Su, Jing', 'Shi, Ping', 'He, En‐Qi', 'Shao, Jie', 'Sun, Na', 'Zu, Rong‐Qiang', 'Yu, Rong‐Bin']",Influenza Other Respir Viruses,,,True
885ca5f85c120048c30b3f74bd2a6ddf9b79736f,PMC,Impact of viral infections in children with community‐acquired pneumonia: results of a study of 17 respiratory viruses,http://dx.doi.org/10.1111/j.1750-2659.2012.00340.x,PMC5780730,22329841,NO-CC CODE,"Please cite this paper as: Esposito et al. (2012) Impact of viral infections in children with community‐acquired pneumonia: results of a study of 17 respiratory viruses. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2012.00340.x. Background  Little is known about the prevalence of viral infections in children with community‐acquired pneumonia (CAP). Objectives  To describe the clinical and virological data collected from children with radiographically confirmed CAP in whom 17 respiratory viruses were sought in respiratory secretion samples during the acute phase of the disease. Patients and methods  The study involved 592 children with radiographically confirmed CAP whose respiratory secretion samples were tested using the Luminex xTAG Respiratory Virus Panel Fast assay, which simultaneously detects influenza A virus, influenza B virus, respiratory syncytial virus (RSV)‐A and ‐B, parainfluenzavirus‐1, ‐2, ‐3, and ‐4, adenovirus, human metapneumovirus, coronaviruses 229E, NL63, OC43, and HKU1, enterovirus/rhinovirus, and bocavirus. A real‐time PCR assay was used to identify the rhinovirus in the enterovirus/rhinovirus‐positive samples. Results  A total of 435 children (73·5%) were positive for at least one virus: the most frequently detected was RSV, which was found in 188 (31·7%), followed by rhinovirus (n = 144, 24·3%), bocavirus (n = 60, 10·1%), influenza viruses (n = 57, 9·6), and hMPV (n = 49, 8·2%). Viral co‐infections were found in 117 children (19·7% of the enrolled children; 26·9% of those with viral infections). Marginal differences were found between the infections owing to a single virus. Co‐infections showed radiographic evidence of alveolar pneumonia significantly more frequently than single infections (OR 1·72, 95% CI 1·05–2·81). Conclusions  The findings of this study highlight the importance of respiratory viruses (mainly RSV and rhinovirus) in children with CAP and show the characteristics of both the single infections and co‐infections associated with the disease.",2013 Jan 13,"['Esposito, Susanna', 'Daleno, Cristina', 'Prunotto, Giulia', 'Scala, Alessia', 'Tagliabue, Claudia', 'Borzani, Irene', 'Fossali, Emilio', 'Pelucchi, Claudio', 'Principi, Nicola']",Influenza Other Respir Viruses,,,True
16519fe598d255bb46c40f7f08d79bf21b3a7ff2,PMC,"Detection of influenza A virus in live bird markets in Kenya, 2009–2011",http://dx.doi.org/10.1111/j.1750-2659.2012.00365.x,PMC5780755,22515746,NO-CC CODE,"Please cite this paper as: Munyua et al. (2013) Detection of influenza A virus in live bird markets in Kenya, 2009–2011. Influenza and Other Respiratory Viruses 7(2), 113–119. Background  Surveillance for influenza viruses within live bird markets (LBMs) has been recognized as an effective tool for detecting circulating avian influenza viruses (AIVs). In Sub‐Saharan Africa, limited data exist on AIVs in animal hosts, and in Kenya the presence of influenza virus in animal hosts has not been described. Objectives  This surveillance project aimed to detect influenza A virus in poultry traded in five LBMs in Kenya. Methods  We visited each market monthly and collected oropharyngeal and cloacal specimens from poultry and environmental specimens for virological testing for influenza A by real time RT‐PCR. On each visit, we collected information on the number and types of birds in each market, health status of the birds, and market practices. Results  During March 24, 2009–February 28, 2011, we collected 5221 cloacal and oropharyngeal swabs. Of the 5199 (99·6%) specimens tested, influenza A virus was detected in 42 (0·8%), including 35/4166 (0·8%) specimens from chickens, 3/381 (0·8%) from turkeys, and 4/335 (1·2%) from geese. None of the 317 duck specimens were positive. Influenza was more commonly detected in oropharyngeal [33 (1·3%)] than in cloacal [9 (0·4%)] specimens. None of the 485 environmental specimens were positive. Virus was detected in all five markets during most (14/22) of the months. Ducks and geese were kept longer at the market (median 30 days) than chickens (median 2 days). Conclusions  Influenza A was detected in a small percentage of poultry traded in LBMs in Kenya. Efforts should be made to promote practices that could limit the maintenance and transmission of AIVs in LBMs.",2013 Mar 19,"['Munyua, Peninah M.', 'Githinji, Jane W.', 'Waiboci, Lilian W.', 'Njagi, Leonard M.', 'Arunga, Geoffrey', 'Mwasi, Lydia', 'Murithi Mbabu, R.', 'Macharia, Joseph M.', 'Breiman, Robert F.', 'Kariuki Njenga, M.', 'Katz, Mark A.']",Influenza Other Respir Viruses,,,True
8a6a728d46caa15618a80746cdac1b0a697f188c,PMC,Human bocavirus amongst an all‐ages population hospitalised with acute lower respiratory infections in Cambodia,http://dx.doi.org/10.1111/j.1750-2659.2012.00369.x,PMC5780762,22531100,NO-CC CODE,"Please cite this paper as: Arnott et al. (2013) Human bocavirus amongst an all‐ages population hospitalised with acute lower respiratory infections in Cambodia. Influenza and Other Respiratory Viruses 7(2) 201–210. Background  Human bocavirus (HBoV) is a novel parvovirus that is associated with respiratory and gastrointestinal tract disease. Objectives  To investigate the prevalence and genetic diversity of HBoV amongst hospitalized patients with acute lower respiratory infection (ALRI) in Cambodia. Study Design  Samples were collected from 2773 patients of all ages hospitalised with symptoms of ALRI between 2007 and 2009. All samples were screened by multiplex RT‐PCR/PCR for 18 respiratory viruses. All samples positive for HBoV were sequenced and included in this study. Results  Of the samples tested, 43 (1·5%) were positive for HBoV. The incidence of HBoV did not vary between the consecutive seasons investigated, and HBoV infections were detected year‐round. The incidence of HBoV infection was highest in patients aged <2 years, with pneumonia or bronchopneumonia the most common clinical diagnosis, regardless of age. A total of 19 patients (44%) were co‐infected with HBoV and an additional respiratory pathogen. All isolates were classified as HBoV type 1 (HBoV‐1). High conservation between Cambodian NP1 and V1V2 gene sequences was observed. Conclusions  Human bocavirus infection can result in serious illness, however is frequently detected in the context of viral co‐infection. Specific studies are required to further understand the true pathogenesis of HBoV in the context of severe respiratory illness.",2013 Mar 25,"['Arnott, Alicia', 'Vong, Sirenda', 'Rith, Sareth', 'Naughtin, Monica', 'Ly, Sowath', 'Guillard, Bertrand', 'Deubel, Vincent', 'Buchy, Philippe']",Influenza Other Respir Viruses,,,True
987177dd5896befd3e45e5d1fae03839b41b320b,PMC,"Community‐acquired respiratory viruses and co‐infection among patients of Ontario sentinel practices, April 2009 to February 2010",http://dx.doi.org/10.1111/j.1750-2659.2012.00418.x,PMC5781002,22883216,NO-CC CODE,"Please cite this paper as: Peci et al. (2012) Community‐acquired respiratory viruses and co‐infection among patients of Ontario Sentinel practices, April 2009 to February 2010. Influenza and Other Respiratory Viruses 7(4), 559–566. Background  Respiratory viruses are known to cocirculate but this has not been described in detail during an influenza pandemic. Objectives  To describe respiratory viruses, including co‐infection and associated attributes such as age, sex or comorbidity, in patients presenting with influenza‐like illness to a community sentinel network, during the pandemic A(H1N1)pdm09 in Ontario, Canada. Methods  Respiratory samples and epidemiologic details were collected from 1018 patients with influenza‐like illness as part of respiratory virus surveillance and a multiprovincial case–control study of influenza vaccine effectiveness. Results  At least one virus was detected in 668 (65·6%) of 1018 samples; 512 (50·3%) had single infections and 156 (15·3%) co‐infections. Of single infections, the most common viruses were influenza A in 304 (59·4%) samples of which 275 (90·5%) were influenza A(H1N1)pdm09, and enterovirus/rhinovirus in 149 (29·1%) samples. The most common co‐infections were influenza A and respiratory syncytial virus B, and influenza A and enterovirus/rhinovirus. In multinomial logistic regression analyses adjusted for age, sex, comorbidity, and timeliness of sample collection, single infection was less often detected in the elderly and co‐infection more often in patients <30 years of age. Co‐infection, but not single infection, was more likely detected in patients who had a sample collected within 2 days of symptom onset as compared to 3–7 days. Conclusions  Respiratory viral co‐infections are commonly detected when using molecular techniques. Early sample collection increases likelihood of detection of co‐infection. Further studies are needed to better understand the clinical significance of viral co‐infection.",2013 Jul 9,"['Peci, Adriana', 'Winter, Anne‐Luise', 'Gubbay, Jonathan B.', 'Skowronski, Danuta M.', 'Balogun, Elizabeth I.', 'De Lima, Cedric', 'Crowcroft, Natasha S.', 'Rebbapragada, Anu']",Influenza Other Respir Viruses,,,True
3b265edacf7baf698286ac29b6ca808bf1dd599b,PMC,Viral and bacterial aetiology of community‐acquired pneumonia in adults,http://dx.doi.org/10.1111/j.1750-2659.2012.00425.x,PMC5781003,22908940,NO-CC CODE,"Please cite this paper as: Huijskens et al. (2012) Viral and bacterial aetiology of community‐acquired pneumonia in adults. Influenza and Other Respiratory Viruses 7(4), 567–573. Background  Modern molecular techniques reveal new information on the role of respiratory viruses in community‐acquired pneumonia. In this study, we tried to determine the prevalence of respiratory viruses and bacteria in patients with community‐acquired pneumonia who were admitted to the hospital. Methods  Between April 2008 and April 2009, 408 adult patients (aged between 20 and 94 years) with community‐acquired pneumonia were tested for the presence of respiratory pathogens using bacterial cultures, real‐time PCR for viruses and bacteria, urinary antigen testing for Legionella and Pneumococci and serology for the presence of viral and bacterial pathogens. Results  Pathogens were identified in 263 (64·5%) of the 408 patients. The most common single organisms in these 263 patients were Streptococcus pneumoniae (22·8%), Coxiella burnetii (6·8%) and influenza A virus (3·8%). Of the 263 patients detected with pathogens, 117 (44·5%) patients were positive for one or more viral pathogens. Of these 117 patients, 52 (44·4%) had no bacterial pathogen. Multiple virus infections (≥2) were found in 16 patients. Conclusion  In conclusion, respiratory viruses are frequently found in patients with CAP and may therefore play an important role in the aetiology of this disease.",2013 Jul 22,"['Huijskens, Elisabeth G. W.', 'van Erkel, Adriana J. M.', 'Palmen, Fernand M. H.', 'Buiting, Anton G. M.', 'Kluytmans, Jan A. J. W.', 'Rossen, John W. A.']",Influenza Other Respir Viruses,,,True
7e951ff88008de16ecc2aeaecea54ed5b5c84abf,PMC,Prevention of influenza among travellers attending at a UK travel clinic: beliefs and perceptions. A cross‐sectional study,http://dx.doi.org/10.1111/irv.12010,PMC5781004,22998606,NO-CC CODE,"Please cite this paper as: Masuet‐Aumatell et al. (2012) Prevention of influenza among travellers attending at a UK travel clinic: beliefs and perceptions. A cross‐sectional study. Influenza and Other Respiratory Viruses 7(4), 574–583. Background  Travellers’ compliance with measures to prevent influenza through the use of antivirals and influenza vaccine remains very poor despite influenza being one of the commonest travel and vaccine‐preventable diseases. A study was undertaken to assess travellers’ beliefs, perceptions and intentions to take antivirals for the treatment and prevention of influenza during the H1N1 pandemic. Methods  A cross‐sectional survey (n = 96) of travellers who attended the Royal Free Travel Health Centre, London, UK was undertaken in September 2009. A self‐administered questionnaire was completed by a traveller in advance of their pre‐travel health consultation. Logistic regression identified variables independently associated with compliance. Results  Influenza vaccination uptake for the 5 years preceding the study was found to be 20·8%. This was statistically significantly higher for older travellers and those with underlying health conditions (P < 0·005). Mean intention to comply with antiviral drugs on a preventive and therapeutic basis was 58% and 72%, respectively, and this varied markedly with age and with dispensed antimalarial chemoprophylaxis. Conclusion  This study identifies some beliefs and perceptions travellers consider with regard to the therapeutic and preventive influenza use of antivirals during the H1N1 pandemic; it underscores the importance of travellers receiving hemisphere appropriate influenza vaccination. The external validity of these study findings requires further corroboration involving other travel clinics and different cohorts of travellers during seasonal activity or outbreaks of influenza. These findings could guide the development of future strategies for the prevention of influenza in travellers.",2013 Jul 24,"['Masuet‐Aumatell, Cristina', 'Toovey, Stephen', 'Zuckerman, Jane N.']",Influenza Other Respir Viruses,,,True
cb42cda59259c534f30ab688560eceec6cc27a7a,PMC,Fatal respiratory distress syndrome due to coronavirus infection in a child with severe combined immunodeficiency,http://dx.doi.org/10.1111/irv.12059,PMC5781196,23199056,NO-CC CODE,"Please cite this paper as: Szczawinska‐Poplonyk et al. (2012) Fatal respiratory distress syndrome due to coronavirus infection in a child with severe combined immunodeficiency. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12059. Coronaviruses have been demonstrated to contribute substantially to respiratory tract infections among the child population. Though infected children commonly present mild upper airway symptoms, in high‐risk patients with underlying conditions, particularly in immunocompromised children these pathogens may lead to severe lung infection and extrapulmonary disorders. In this paper, we provide the first report of the case of a 15‐month‐old child with severe combined immunodeficiency and coronavirus HKU1‐related pneumonia with fatal respiratory distress syndrome.",2013 Sep 30,"['Szczawinska‐Poplonyk, Aleksandra', 'Jonczyk‐Potoczna, Katarzyna', 'Breborowicz, Anna', 'Bartkowska‐Sniatkowska, Alicja', 'Figlerowicz, Magdalena']",Influenza Other Respir Viruses,,,True
a72d5d201c57555d5e5aa89d881ab2e1a90f9725,PMC,1125 Viral Infections In Outpatients With Medically Attended Acute Respiratory Illness During the 2012-13 Influenza Season,http://dx.doi.org/10.1093/ofid/ofu052.833,PMC5781443,,NO-CC CODE,,2014 Dec,"['Zimmerman, Richard K.', 'Rinaldo, Charles R.', 'Nowalk, Mary Patricia', 'K, Balasubramani Goundappa', 'Moehling, Krissy', 'Bullotta, Arlene', 'Wisniewski, Stephen']",Open Forum Infect Dis,,,False
22fa521b820ddd3ead7ed865fbf69fb998b8dbe9,PMC,131 Changes in clinical presentation and epidemiology of respiratory pathogens associated with upper respiratory infection in military trainees following reintroduction of adenovirus vaccine,http://dx.doi.org/10.1093/ofid/ofu051.39,PMC5781560,,NO-CC CODE,,2014 Dec,"['Young, Adam', 'Valtier, Sandra', 'Lott, Lisa', 'Cropper, Thomas L.', 'Yun, Heather C.']",Open Forum Infect Dis,,,False
350c317f6048b4c7d8b1f7fbd82bc38bdfa3c09a,PMC,"787 Respiratory Pathogen Detection in Cases of Severe Acute Respiratory Illness (SARI) Among Hospitalized Patients at Two Metro-Area Hospitals, Minnesota, 2013-2014",http://dx.doi.org/10.1093/ofid/ofu052.495,PMC5781604,,NO-CC CODE,,2014 Dec,"['Friedlander, Hannah', 'Como-Sabetti, Kathryn']",Open Forum Infect Dis,,,False
468844b0ac564dffab61eda4ef2e275d0cd2c329,PMC,797 Viral co-infections in hospitalized patients with respiratory tract infections,http://dx.doi.org/10.1093/ofid/ofu052.505,PMC5781746,,NO-CC CODE,,2014 Dec,"['Al-Nakib, Widad', 'Essa, Sahar', 'Altawalah, Haya', 'Owayed, Abdullah', 'Khadadah, Mousa', 'Behbehani, Nasser']",Open Forum Infect Dis,,,False
51b95264ed1f6450ee03ba62451b5d676dbf4708,PMC,429 Diagnosis and Treatment of Respiratory Syncytial Virus in Immunocompromised Hosts in Large Midwestern Transplant Centers,http://dx.doi.org/10.1093/ofid/ofu052.295,PMC5781854,,NO-CC CODE,,2014 Dec,"['Beaird, Omer', 'Freifeld, Alison', 'Ison, Michael', 'Lawrence, Steven', 'Theodoropoulos, Nicole', 'Clark, Nina', 'Razonable, Raymund R.', 'Alangaden, George', 'Miller, Rachel', 'Smith, Jeannina', 'Young, Jo-Anne', 'Hawkinson, Dana', 'Kaul, Daniel']",Open Forum Infect Dis,,,False
244b7bb1550da26f65bdf97fee84a26623c1dd5e,PMC,807 Relationship between Respiratory Virus Infection and Pneumococcal Colonization in Children,http://dx.doi.org/10.1093/ofid/ofu052.515,PMC5781949,,NO-CC CODE,,2014 Dec,"['Cho, Eun Young', 'Lee, Hyeonseung', 'Kang, Hyun Mi', 'Yoon, In Ae', 'Jung, Hyun Joo', 'Choe, Young June', 'Choi, Jae Hong', 'Lee, Hyunju', 'Choi, Eun Hwa', 'Lee, Hoan Jong']",Open Forum Infect Dis,,,False
a6405291e8afd523d5893a3ddd618ab18d8b2025,PMC,766 Clinical Features and Outcome of Patients with Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) Infection,http://dx.doi.org/10.1093/ofid/ofu052.474,PMC5781957,,NO-CC CODE,,2014 Dec,"['Alraddadi, Basem', 'Bawareth, Noha', 'Omar, Haneen', 'Alsalmi, Hanadi', 'Feteih, Maun', 'Wali, Ghassan']",Open Forum Infect Dis,,,False
827c76934c1aa36097ed5369dca6132d7932fcde,PMC,1143 GenMark ESensor Respiratory Viral Panel in an Inpatient Pediatric Population,http://dx.doi.org/10.1093/ofid/ofu052.851,PMC5782103,,NO-CC CODE,,2014 Dec,"['Oliver, Sara', 'Potter, Jennifer', 'Covington, Richard', 'Tipler, Kelly', 'Kimberlin, David W.', 'Prichard, Mark N.']",Open Forum Infect Dis,,,False
ac1372121c1cfa24c7f1cfca088b69f453466522,PMC,1482 Sentinel Surveillance of Respiratory Viral Pathogens in Border Areas of Western Cambodia,http://dx.doi.org/10.1093/ofid/ofu052.1028,PMC5782267,,NO-CC CODE,,2014 Dec,"['Chuang, Ilin', 'Timmermans, Ans', 'Melendrez, Melanie', 'Se, Youry', 'Nou, Samon', 'Uthaimongkol, Nichapat', 'Tyner, Stuart', 'Rith, Sareth', 'Jarman, Rick', 'Bethell, Delia', 'Chanarat, Nitima', 'Pavlin, Julie', 'Wongstitwilairoong, Tippa', 'Saingam, Piyaporn', 'Buth, Sam El', 'Touch, Sok', 'Heng, Seng', 'Sovann, Ly', 'Lon, Chanthap', 'Fernandez, Stefan', 'Buchy, Philippe', 'Saunders, David']",Open Forum Infect Dis,,,False
d6303899bb27b192349eb8f8a8f5498cdc963ccd,PMC,"Trends in Infectious Disease Mortality, South Korea, 1983–2015",http://dx.doi.org/10.3201/eid2402.170862,PMC5782883,29350153,NO-CC CODE,"We used national statistics from 1983–2015 to evaluate trends in mortality caused by infectious diseases in South Korea. Age-standardized mortality from infectious disease decreased from 43.5/100,000 population in 1983 to 16.5/100,000 in 1996, and then increased to 44.6/100,000 in 2015. Tuberculosis was the most common cause of death in 1983 and respiratory tract infections in 2015. We observed a significant decline in infant deaths caused by infectious diseases, but mortality in persons age >65 years increased from 135 deaths/100,000 population in 1996 to 307/100,000 in 2015. The relative inequality indices for respiratory tract infections, sepsis, and tuberculosis tended to increase over time. Although substantial progress has been achieved in terms of infant mortality, death rates from infectious disease has not decreased overall. Elderly populations with lower education levels and subgroups susceptible to respiratory infections and sepsis should be the focus of preventive policies.",2018 Feb,"['Choe, Young June', 'Choe, Seung-Ah', 'Cho, Sung-Il']",Emerg Infect Dis,,,True
76fa539727b0df902f541bf999c6b3912207fd8c,PMC,"Influenza D Virus in Cattle, Ireland",http://dx.doi.org/10.3201/eid2402.170759,PMC5782902,29350168,NO-CC CODE,We detected influenza D virus in 18 nasal swab samples from cattle in Ireland that were clinically diagnosed with respiratory disease. Specimens were obtained from archived samples received for routine diagnosis during 2014–2016. Sequencing showed that viruses from Ireland clustered with virus sequences obtained in Europe within the D/swine/OK/1334/2011 clade.,2018 Feb,"['Flynn, Orla', 'Gallagher, Clare', 'Mooney, Jean', 'Irvine, Claire', 'Ducatez, Mariette', 'Hause, Ben', 'McGrath, Guy', 'Ryan, Eoin']",Emerg Infect Dis,,,True
fac5b238ab17b9bab4be4131a46c7509f841e70e,PMC,"Influenza D Virus in Cattle, Ireland",http://dx.doi.org/10.3201/eid2402.170759,PMC5782902,29350168,NO-CC CODE,We detected influenza D virus in 18 nasal swab samples from cattle in Ireland that were clinically diagnosed with respiratory disease. Specimens were obtained from archived samples received for routine diagnosis during 2014–2016. Sequencing showed that viruses from Ireland clustered with virus sequences obtained in Europe within the D/swine/OK/1334/2011 clade.,2018 Feb,"['Flynn, Orla', 'Gallagher, Clare', 'Mooney, Jean', 'Irvine, Claire', 'Ducatez, Mariette', 'Hause, Ben', 'McGrath, Guy', 'Ryan, Eoin']",Emerg Infect Dis,,,False
c6e964e7a3f4cb45e146546ae2aef10017fe69d4,PMC,"Whole-Genome Sequence of Human Rhinovirus C47, Isolated from an Adult Respiratory Illness Outbreak in Butte County, California, 2017",http://dx.doi.org/10.1128/genomeA.01579-17,PMC5794959,29437112,NO-CC CODE,"Here, we report the full coding sequence of rhinovirus C47 (RV-C47), obtained from a patient respiratory sample collected during an acute respiratory illness investigation in Butte County, California, in January 2017. This is the first whole-genome sequence of RV-C47 to be reported.",2018 Feb 1,"['Pan, Chao-Yang', 'Padilla, Tasha', 'Yagi, Shigeo', 'Lewis, Linda S.', 'Ng, Terry Fei Fan', 'Marine, Rachel L.', 'Nix, William Allan', 'Wadford, Debra A.']",Genome Announc,,,True
9e8a62fc036d8dc6b63def0a7812b07e11021d51,PMC,Infectious Diseases Continued to be the World's Core Challenge,,PMC5811935,29487465,NO-CC CODE,,2017 Nov,"Haileamlak, Abraham",Ethiop J Health Sci,,,True
40f51d700f24dd40b22d574cb92f5eb1edfe288c,PMC,The Global Polio Laboratory Network as a Platform for the Viral Vaccine-Preventable and Emerging Diseases Laboratory Networks,http://dx.doi.org/10.1093/infdis/jix092,PMC5853949,28838192,NO-CC CODE,"The Global Polio Laboratory Network (GPLN) began building in the late 1980s on a 3-tiered structure of 146 laboratories with different and complementary technical and support capacities (poliovirus isolation, molecular strain characterization including sequencing, quality assurance, and research). The purpose of this network is to provide timely and accurate laboratory results to the Global Polio Eradication Initiative. Deeply integrated with field case-based surveillance, it ultimately provides molecular epidemiological data from polioviruses used to inform programmatic and immunization activities. This network of global coverage requires substantial investments in laboratory infrastructure, equipment, supplies, reagents, quality assurance, staffing and training, often in resource-limited settings. The GPLN has not only developed country capacities, but it also serves as a model to other global laboratory networks for vaccine-preventable diseases that will endure after the polio eradication goal is achieved. Leveraging lessons learned during past 27 years, the authors discuss options for transitioning GPLN assets to support control of other viral vaccine-preventable, emerging, and reemerging diseases.",2017 Jul 1,"['Diop, Ousmane M.', 'Kew, Olen M.', 'de Gourville, Esther M.', 'Pallansch, Mark A.']",J Infect Dis,,,True
ee8a6b2db7d43dedd8668300d2e71587a3062f17,PMC,Influenza surveillance in Europe: establishing epidemic thresholds by the Moving Epidemic Method,http://dx.doi.org/10.1111/j.1750-2659.2012.00422.x,PMC5855152,22897919,NO-CC CODE,"Please cite this paper as: Vega et al. (2012) Influenza surveillance in Europe: establishing epidemic thresholds by the moving epidemic method. Influenza and Other Respiratory Viruses 7(4), 546–558. Background  Timely influenza surveillance is important to monitor influenza epidemics. Objectives  (i) To calculate the epidemic threshold for influenza‐like illness (ILI) and acute respiratory infections (ARI) in 19 countries, as well as the thresholds for different levels of intensity. (ii) To evaluate the performance of these thresholds. Methods  The moving epidemic method (MEM) has been developed to determine the baseline influenza activity and an epidemic threshold. False alerts, detection lags and timeliness of the detection of epidemics were calculated. The performance was evaluated using a cross‐validation procedure. Results  The overall sensitivity of the MEM threshold was 71·8% and the specificity was 95·5%. The median of the timeliness was 1 week (range: 0–4·5). Conclusions  The method produced a robust and specific signal to detect influenza epidemics. The good balance between the sensitivity and specificity of the epidemic threshold to detect seasonal epidemics and avoid false alerts has advantages for public health purposes. This method may serve as standard to define the start of the annual influenza epidemic in countries in Europe.",2013 Jul 16,"['Vega, Tomás', 'Lozano, Jose Eugenio', 'Meerhoff, Tamara', 'Snacken, René', 'Mott, Joshua', 'Ortiz de Lejarazu, Raul', 'Nunes, Baltazar']",Influenza Other Respir Viruses,,,True
b5f7f394b121c84ea076571e10b4a4b1bad7e344,PMC,Influence of Population Immunosuppression and Past Vaccination on Smallpox Reemergence,http://dx.doi.org/10.3201/eid2404.171233,PMC5875263,29553311,NO-CC CODE,"We built a SEIR (susceptible, exposed, infected, recovered) model of smallpox transmission for New York, New York, USA, and Sydney, New South Wales, Australia, that accounted for age-specific population immunosuppression and residual vaccine immunity and conducted sensitivity analyses to estimate the effect these parameters might have on smallpox reemergence. At least 19% of New York’s and 17% of Sydney’s population are immunosuppressed. The highest smallpox infection rates were in persons 0–19 years of age, but the highest death rates were in those >45 years of age. Because of the low level of residual vaccine immunity, immunosuppression was more influential than vaccination on death and infection rates in our model. Despite widespread smallpox vaccination until 1980 in New York, smallpox outbreak severity appeared worse in New York than in Sydney. Immunosuppression is highly prevalent and should be considered in future smallpox outbreak models because excluding this factor probably underestimates death and infection rates.",2018 Apr,"['MacIntyre, C. Raina', 'Costantino, Valentina', 'Chen, Xin', 'Segelov, Eva', 'Chughtai, Abrar Ahmad', 'Kelleher, Anthony', 'Kunasekaran, Mohana', 'Lane, John Michael']",Emerg Infect Dis,,,True
43d1ea78fb9a694f81e590f387cbcff0b7d0073f,PMC,Influence of Population Immunosuppression and Past Vaccination on Smallpox Reemergence,http://dx.doi.org/10.3201/eid2404.171233,PMC5875263,29553311,NO-CC CODE,"We built a SEIR (susceptible, exposed, infected, recovered) model of smallpox transmission for New York, New York, USA, and Sydney, New South Wales, Australia, that accounted for age-specific population immunosuppression and residual vaccine immunity and conducted sensitivity analyses to estimate the effect these parameters might have on smallpox reemergence. At least 19% of New York’s and 17% of Sydney’s population are immunosuppressed. The highest smallpox infection rates were in persons 0–19 years of age, but the highest death rates were in those >45 years of age. Because of the low level of residual vaccine immunity, immunosuppression was more influential than vaccination on death and infection rates in our model. Despite widespread smallpox vaccination until 1980 in New York, smallpox outbreak severity appeared worse in New York than in Sydney. Immunosuppression is highly prevalent and should be considered in future smallpox outbreak models because excluding this factor probably underestimates death and infection rates.",2018 Apr,"['MacIntyre, C. Raina', 'Costantino, Valentina', 'Chen, Xin', 'Segelov, Eva', 'Chughtai, Abrar Ahmad', 'Kelleher, Anthony', 'Kunasekaran, Mohana', 'Lane, John Michael']",Emerg Infect Dis,,,True
3184616f8c024012a6d2d460222d2fb5e56fd98a,PMC,A public antibody lineage that potently inhibits malaria infection by dual binding to the circumsporozoite protein,http://dx.doi.org/10.1038/nm.4513,PMC5893353,29554084,NO-CC CODE,"Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZ) has been shown to be protective, but the features of the antibody response induced by this treatment remain unclear. To investigate this response at high resolution, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized by repeated injection of irradiated PfSPZ and who were found to be protected from controlled human malaria infection (CHMI) with infectious homologous PfSPZ. All IgG monoclonals isolated bound to P. falciparum circumsporozoite protein (PfCSP) and recognized distinct epitopes in the N-terminus, NANP repeat region, and C-terminus. Strikingly, the most effective antibodies, as assessed in a humanized mouse model, bound not only to the repeat region, but also to a minimal peptide at the PfCSP N-terminal junction that is not in the RTS,S vaccine. These dual-specific antibodies were isolated from different donors and used VH3-30 or VH3-33 alleles carrying tryptophan or arginine at position 52. Using structural and mutational data, we describe the elements required for germline recognition and affinity maturation. Our study provides potent neutralizing antibodies and relevant information for lineage-targeted vaccine design and immunization strategies.",2018 May 19,"['Tan, Joshua', 'Sack, Brandon K', 'Oyen, David', 'Zenklusen, Isabelle', 'Piccoli, Luca', 'Barbieri, Sonia', 'Foglierini, Mathilde', 'Fregni, Chiara Silacci', 'Marcandalli, Jessica', 'Jongo, Said', 'Abdulla, Salim', 'Perez, Laurent', 'Corradin, Giampietro', 'Varani, Luca', 'Sallusto, Federica', 'Sim, B Kim Lee', 'Hoffman, Stephen L', 'Kappe, Stefan H I', 'Daubenberger, Claudia', 'Wilson, Ian A', 'Lanzavecchia, Antonio']",Nat Med,,,True
6a875d8af8a46c77a7a5357d722e9cfaa1fad7ea,PMC,A public antibody lineage that potently inhibits malaria infection by dual binding to the circumsporozoite protein,http://dx.doi.org/10.1038/nm.4513,PMC5893353,29554084,NO-CC CODE,"Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZ) has been shown to be protective, but the features of the antibody response induced by this treatment remain unclear. To investigate this response at high resolution, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized by repeated injection of irradiated PfSPZ and who were found to be protected from controlled human malaria infection (CHMI) with infectious homologous PfSPZ. All IgG monoclonals isolated bound to P. falciparum circumsporozoite protein (PfCSP) and recognized distinct epitopes in the N-terminus, NANP repeat region, and C-terminus. Strikingly, the most effective antibodies, as assessed in a humanized mouse model, bound not only to the repeat region, but also to a minimal peptide at the PfCSP N-terminal junction that is not in the RTS,S vaccine. These dual-specific antibodies were isolated from different donors and used VH3-30 or VH3-33 alleles carrying tryptophan or arginine at position 52. Using structural and mutational data, we describe the elements required for germline recognition and affinity maturation. Our study provides potent neutralizing antibodies and relevant information for lineage-targeted vaccine design and immunization strategies.",2018 May 19,"['Tan, Joshua', 'Sack, Brandon K', 'Oyen, David', 'Zenklusen, Isabelle', 'Piccoli, Luca', 'Barbieri, Sonia', 'Foglierini, Mathilde', 'Fregni, Chiara Silacci', 'Marcandalli, Jessica', 'Jongo, Said', 'Abdulla, Salim', 'Perez, Laurent', 'Corradin, Giampietro', 'Varani, Luca', 'Sallusto, Federica', 'Sim, B Kim Lee', 'Hoffman, Stephen L', 'Kappe, Stefan H I', 'Daubenberger, Claudia', 'Wilson, Ian A', 'Lanzavecchia, Antonio']",Nat Med,,,False
4806820559d07cf620ffe66a28c8ac74e34b2183,PMC,A public antibody lineage that potently inhibits malaria infection by dual binding to the circumsporozoite protein,http://dx.doi.org/10.1038/nm.4513,PMC5893353,29554084,NO-CC CODE,"Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZ) has been shown to be protective, but the features of the antibody response induced by this treatment remain unclear. To investigate this response at high resolution, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized by repeated injection of irradiated PfSPZ and who were found to be protected from controlled human malaria infection (CHMI) with infectious homologous PfSPZ. All IgG monoclonals isolated bound to P. falciparum circumsporozoite protein (PfCSP) and recognized distinct epitopes in the N-terminus, NANP repeat region, and C-terminus. Strikingly, the most effective antibodies, as assessed in a humanized mouse model, bound not only to the repeat region, but also to a minimal peptide at the PfCSP N-terminal junction that is not in the RTS,S vaccine. These dual-specific antibodies were isolated from different donors and used VH3-30 or VH3-33 alleles carrying tryptophan or arginine at position 52. Using structural and mutational data, we describe the elements required for germline recognition and affinity maturation. Our study provides potent neutralizing antibodies and relevant information for lineage-targeted vaccine design and immunization strategies.",2018 May 19,"['Tan, Joshua', 'Sack, Brandon K', 'Oyen, David', 'Zenklusen, Isabelle', 'Piccoli, Luca', 'Barbieri, Sonia', 'Foglierini, Mathilde', 'Fregni, Chiara Silacci', 'Marcandalli, Jessica', 'Jongo, Said', 'Abdulla, Salim', 'Perez, Laurent', 'Corradin, Giampietro', 'Varani, Luca', 'Sallusto, Federica', 'Sim, B Kim Lee', 'Hoffman, Stephen L', 'Kappe, Stefan H I', 'Daubenberger, Claudia', 'Wilson, Ian A', 'Lanzavecchia, Antonio']",Nat Med,,,False
bcf3535d0d3202f99376dcbeb668880cd2dcb741,PMC,A public antibody lineage that potently inhibits malaria infection by dual binding to the circumsporozoite protein,http://dx.doi.org/10.1038/nm.4513,PMC5893353,29554084,NO-CC CODE,"Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZ) has been shown to be protective, but the features of the antibody response induced by this treatment remain unclear. To investigate this response at high resolution, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized by repeated injection of irradiated PfSPZ and who were found to be protected from controlled human malaria infection (CHMI) with infectious homologous PfSPZ. All IgG monoclonals isolated bound to P. falciparum circumsporozoite protein (PfCSP) and recognized distinct epitopes in the N-terminus, NANP repeat region, and C-terminus. Strikingly, the most effective antibodies, as assessed in a humanized mouse model, bound not only to the repeat region, but also to a minimal peptide at the PfCSP N-terminal junction that is not in the RTS,S vaccine. These dual-specific antibodies were isolated from different donors and used VH3-30 or VH3-33 alleles carrying tryptophan or arginine at position 52. Using structural and mutational data, we describe the elements required for germline recognition and affinity maturation. Our study provides potent neutralizing antibodies and relevant information for lineage-targeted vaccine design and immunization strategies.",2018 May 19,"['Tan, Joshua', 'Sack, Brandon K', 'Oyen, David', 'Zenklusen, Isabelle', 'Piccoli, Luca', 'Barbieri, Sonia', 'Foglierini, Mathilde', 'Fregni, Chiara Silacci', 'Marcandalli, Jessica', 'Jongo, Said', 'Abdulla, Salim', 'Perez, Laurent', 'Corradin, Giampietro', 'Varani, Luca', 'Sallusto, Federica', 'Sim, B Kim Lee', 'Hoffman, Stephen L', 'Kappe, Stefan H I', 'Daubenberger, Claudia', 'Wilson, Ian A', 'Lanzavecchia, Antonio']",Nat Med,,,False
da0909be44cbe1d49c642442e6eb0c772171a307,PMC,"Viral pneumonia in adults and older children in sub-Saharan Africa — epidemiology, aetiology, diagnosis and management",http://dx.doi.org/10.15172/pneu.2014.5/446,PMC5922328,31641571,NO-CC CODE,"Community-acquired pneumonia causes substantial morbidity and mortality in sub-Saharan Africa with an estimated 131 million new cases each year. Viruses — such as influenza virus, respiratory syncytial virus and parainfluenza virus — are now recognised as important causes of respiratory disease in older children and adults in the developed world following the emergence of sensitive molecular diagnostic tests, recent severe viral epidemics, and the discovery of novel viruses. Few studies have comprehensively evaluated the viral aetiology of adult pneumonia in Africa, but it is likely to differ from Western settings due to varying seasonality and the high proportion of patients with immunosuppression and co-morbidities. Emerging data suggest a high prevalence of viral pathogens, as well as multiple viral and viral/bacterial infections in African adults with pneumonia. However, the interpretation of positive results from highly sensitive polymerase chain reaction tests can be challenging. Therapeutic and preventative options against viral respiratory infections are currently limited in the African setting. This review summarises the current state of the epidemiology, aetiology, diagnosis and management of viral pneumonia in sub-Saharan Africa.",2014 Dec 1,"Ho, Antonia",Pneumonia (Nathan),,,False
d9714f0e1a8efe98e861a27e8f03f2ca1844c7b4,PMC,Standardisation and evaluation of a quantitative multiplex real-time PCR assay for the rapid identification of Streptococcus pneumoniae,http://dx.doi.org/10.15172/pneu.2015.6/559,PMC5922331,31641579,NO-CC CODE,"Rapid diagnosis of Streptococcus pneumoniae can play a significant role in decreasing morbidity and mortality of infection. The accurate diagnosis of pneumococcal disease is hampered by the difficulties in growing the isolates from clinical specimens and also by misidentification. Molecular methods have gained popularity as they offer improvement in the detection of causative pathogens with speed and ease. The present study aims at validating and standardising the use of 4 oligonucleotide primer-probe sets (pneumolysin [ply], autolysin [lytA], pneumococcal surface adhesion A [psaA] and Spn9802 [DNA fragment]) in a single-reaction mixture for the detection and discrimination of S. pneumoniae. Here, we validate a quantitative multiplex real-time PCR (qmPCR) assay with a panel consisting of 43 S. pneumoniae and 29 non-pneumococcal isolates, 20 culture positive, 26 culture negative and 30 spiked serum samples. A standard curve was obtained using S. pneumoniae ATCC 49619 strain and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene was used as an endogenous internal control. The experiment showed high sensitivity with lower limit of detection equivalent to 4 genome copies/µl. The efficiency of the reaction was 100% for ply, lytA, Spn9802 and 97% for psaA. The test showed sensitivity and specificity of 100% with culture isolates and serum specimens. This study demonstrates that qmPCR analysis of sera using 4 oligonucleotide primers appears to be an appropriate method for the genotypic identification of S. pneumoniae infection.",2015 Dec 1,"['Ganaie, Feroze A.', 'Govindan, Vandana', 'Ravi Kumar, K. L.']",Pneumonia (Nathan),,,False
d6bc3b70f8ee04ee9bb00e4aa98c89c4290b125a,PMC,Upper airway viruses and bacteria detection in clinical pneumonia in a population with high nasal colonisation do not relate to clinical signs,http://dx.doi.org/10.15172/pneu.2015.6/636,PMC5922338,31641578,NO-CC CODE,"Indigenous Australian children have high (up to 90%) rates of nasopharyngeal microbial colonisation and of hospitalisation for pneumonia. In Indigenous children hospitalised with pneumonia in Central Australia, we describe the nasopharyngeal detection of viruses and bacteria and assessed whether their presence related to signs of pneumonia (tachypnoea and/or chest in-drawing) on hospital admission and during subsequent days. Nasopharyngeal swabs (NPS) and data were prospectively collected from 145 children (median age = 23.5 months, interquartile range [IQR] 8.7–50) hospitalised with pneumonia at Alice Springs Hospital, Australia, between April 2001 and July 2002. The cohort was enrolled in a randomised controlled study using zinc and/or vitamin A supplementation. NPS were taken within 24 hours of hospitalisation and kept frozen at-80°C until analysed in 2014. Polymerase chain reaction (PCR) was used to detect Moraxella catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, Chlamydophila pneumoniae, Mycoplasma pneumoniae, and 16 respiratory viruses. Uni- and multi-variate analyses were used to examine the relationships. One or more organisms were present in 137 (94.5%) NPS; 133 (91.7%) detected ≥ 1 bacterium, 34 (37.2%) for ≥ 1 virus and 50 (34.5%) were positive for both viruses and bacteria. C. pneumoniae (n = 3) and M. pneumoniae (n = 2) were rare. In multi-variate analyses, age < 12 months (odds ratio [OR] 6.6 [95% confidence interval {CI} 1.7–25.4]) and fever (OR 4.1 [95% CI 1.7–10.4]) were associated with tachypnoea and chest in-drawing. However the presence of bacteria and/or virus type was not associated with tachypnoea and/or chest in-drawing on admission or during recovery. In children with high nasopharyngeal microbial colonisation rates, the utility of NPS in determining the diagnosis of clinical pneumonia or duration of tachypnoea or in-drawing is likely limited. Larger cohort and case-control studies are required to confirm our findings.",2015 Dec 1,"['Chang, Anne B.', 'Smith-Vaughan, Heidi', 'Sloots, Theo P.', 'Valery, Patricia C.', 'Whiley, David', 'Beissbarth, Jemima', 'Torzillo, Paul J.']",Pneumonia (Nathan),,,True
7ace0702799106bdfe7ae8f837ed785de469075c,PMC,Acute fibrinous and organising pneumonia following lung transplantation is associated with severe allograft dysfunction and poor outcome: a case series,http://dx.doi.org/10.15172/pneu.2015.6/648,PMC5922339,31641580,NO-CC CODE,"Acute fibrinous and organising pneumonia (AFOP) is a histopathologic variant of acute lung injury that has been associated with infection and inflammatory disorders and has been reported as a complication of lung transplantation. A retrospective chart review was performed for all patients transplanted at the University of Wisconsin Hospital and Clinics from January 1995 to December 2013 (n = 561). We identified 6 recipients whose clinical course was complicated by AFOP. All recipients were found to have AFOP on lung biopsy or at post-mortem examination, and 5 of the 6 patients suffered progressive allograft dysfunction that led to fatal outcome. Only 1 of the 6 patients stabilised with augmented immunosuppression and had subsequent improvement and stabilisation of allograft function. We could not clearly identify any specific cause of AFOP, such as drug toxicity or infection. Lung transplantation can be complicated by lung injury with an AFOP pattern on histopathologic examination of lung biopsy specimens. The presence of an AFOP pattern was associated with irreversible decline in lung function that was refractory to therapeutic interventions in 5 of our 6 cases and was associated with severe allograft dysfunction and death in these 5 individuals. AFOP should be considered as a potential diagnosis when lung transplant recipients develop progressive decline in lung function that is consistent with a clinical diagnosis of chronic lung allograft dysfunction.",2015 Dec 1,"['Meyer, Keith C.', 'Bierach, Jennifer', 'Kanne, Jeffrey', 'Torrealba, Jose R.', 'De Oliveira, Nilto C.']",Pneumonia (Nathan),,,False
667d842d13def9658375872a415e504f0945dcfe,PMC,"Middle East Respiratory Syndrome Coronavirus Antibodies in Dromedary Camels, Bangladesh, 2015",http://dx.doi.org/10.3201/eid2405.171192,PMC5938793,29664373,NO-CC CODE,"Dromedary camels are bred domestically and imported into Bangladesh. In 2015, of 55 camels tested for Middle East respiratory syndrome coronavirus in Dhaka, 17 (31%) were seropositive, including 1 bred locally. None were PCR positive. The potential for infected camels in urban markets could have public health implications and warrants further investigation.",2018 May,"['Islam, Ariful', 'Epstein, Jonathan H.', 'Rostal, Melinda K.', 'Islam, Shariful', 'Rahman, Mohammed Ziaur', 'Hossain, Mohammed Enayet', 'Uzzaman, Mohammed Salim', 'Munster, Vincent J.', 'Peiris, Malik', 'Flora, Meerjady Sabrina', 'Rahman, Mahmudur', 'Daszak, Peter']",Emerg Infect Dis,,,True
8d844018f87bef7bc1fdc3fb0197b2239cbbefb3,PMC,"Middle East Respiratory Syndrome Coronavirus Antibodies in Dromedary Camels, Bangladesh, 2015",http://dx.doi.org/10.3201/eid2405.171192,PMC5938793,29664373,NO-CC CODE,"Dromedary camels are bred domestically and imported into Bangladesh. In 2015, of 55 camels tested for Middle East respiratory syndrome coronavirus in Dhaka, 17 (31%) were seropositive, including 1 bred locally. None were PCR positive. The potential for infected camels in urban markets could have public health implications and warrants further investigation.",2018 May,"['Islam, Ariful', 'Epstein, Jonathan H.', 'Rostal, Melinda K.', 'Islam, Shariful', 'Rahman, Mohammed Ziaur', 'Hossain, Mohammed Enayet', 'Uzzaman, Mohammed Salim', 'Munster, Vincent J.', 'Peiris, Malik', 'Flora, Meerjady Sabrina', 'Rahman, Mahmudur', 'Daszak, Peter']",Emerg Infect Dis,,,False
ee13a8332bcf2df6a68e2190a337a0cbaa161281,PMC,"Variation in DNA-Damage Responses to an Inhalational Carcinogen (1,3-Butadiene) in Relation to Strain-Specific Differences in Chromatin Accessibility and Gene Transcription Profiles in C57BL/6J and CAST/EiJ Mice",http://dx.doi.org/10.1289/EHP1937,PMC5944832,29038090,NO-CC CODE,"BACKGROUND: The damaging effects of exposure to environmental toxicants differentially affect genetically distinct individuals, but the mechanisms contributing to these differences are poorly understood. Genetic variation affects the establishment of the gene regulatory landscape and thus gene expression, and we hypothesized that this contributes to the observed heterogeneity in individual responses to exogenous cellular insults. OBJECTIVES: We performed an in vivo study of how genetic variation and chromatin organization may dictate susceptibility to DNA damage, and influence the cellular response to such damage, caused by an environmental toxicant. MATERIALS AND METHODS: We measured DNA damage, messenger RNA (mRNA) and microRNA (miRNA) expression, and genome-wide chromatin accessibility in lung tissue from two genetically divergent inbred mouse strains, C57BL/6J and CAST/EiJ, both in unexposed mice and in mice exposed to a model DNA-damaging chemical, 1,3-butadiene. RESULTS: Our results showed that unexposed CAST/EiJ and C57BL/6J mice have very different chromatin organization and transcription profiles in the lung. Importantly, in unexposed CAST/EiJ mice, which acquired relatively less 1,3-butadiene-induced DNA damage, we observed increased transcription and a more accessible chromatin landscape around genes involved in detoxification pathways. Upon chemical exposure, chromatin was significantly remodeled in the lung of C57BL/6J mice, a strain that acquired higher levels of 1,3-butadiene–induced DNA damage, around the same genes, ultimately resembling the molecular profile of CAST/EiJ. CONCLUSIONS: These results suggest that strain-specific changes in chromatin and transcription in response to chemical exposure lead to a “compensation” for underlying genetic-driven interindividual differences in the baseline chromatin and transcriptional state. This work represents an example of how chemical and environmental exposures can be evaluated to better understand gene-by-environment interactions, and it demonstrates the important role of chromatin response in transcriptomic changes and, potentially, in deleterious effects of exposure. https://doi.org/10.1289/EHP1937",2017 Oct 16,"['Chappell, Grace A.', 'Israel, Jennifer W.', 'Simon, Jeremy M.', 'Pott, Sebastian', 'Safi, Alexias', 'Eklund, Karl', 'Sexton, Kenneth G.', 'Bodnar, Wanda', 'Lieb, Jason D.', 'Crawford, Gregory E.', 'Rusyn, Ivan', 'Furey, Terrence S.']",Environ Health Perspect,,,True
7378dae0e12c996f962f80469b9fcf5d0761d468,PMC,"Variation in DNA-Damage Responses to an Inhalational Carcinogen (1,3-Butadiene) in Relation to Strain-Specific Differences in Chromatin Accessibility and Gene Transcription Profiles in C57BL/6J and CAST/EiJ Mice",http://dx.doi.org/10.1289/EHP1937,PMC5944832,29038090,NO-CC CODE,"BACKGROUND: The damaging effects of exposure to environmental toxicants differentially affect genetically distinct individuals, but the mechanisms contributing to these differences are poorly understood. Genetic variation affects the establishment of the gene regulatory landscape and thus gene expression, and we hypothesized that this contributes to the observed heterogeneity in individual responses to exogenous cellular insults. OBJECTIVES: We performed an in vivo study of how genetic variation and chromatin organization may dictate susceptibility to DNA damage, and influence the cellular response to such damage, caused by an environmental toxicant. MATERIALS AND METHODS: We measured DNA damage, messenger RNA (mRNA) and microRNA (miRNA) expression, and genome-wide chromatin accessibility in lung tissue from two genetically divergent inbred mouse strains, C57BL/6J and CAST/EiJ, both in unexposed mice and in mice exposed to a model DNA-damaging chemical, 1,3-butadiene. RESULTS: Our results showed that unexposed CAST/EiJ and C57BL/6J mice have very different chromatin organization and transcription profiles in the lung. Importantly, in unexposed CAST/EiJ mice, which acquired relatively less 1,3-butadiene-induced DNA damage, we observed increased transcription and a more accessible chromatin landscape around genes involved in detoxification pathways. Upon chemical exposure, chromatin was significantly remodeled in the lung of C57BL/6J mice, a strain that acquired higher levels of 1,3-butadiene–induced DNA damage, around the same genes, ultimately resembling the molecular profile of CAST/EiJ. CONCLUSIONS: These results suggest that strain-specific changes in chromatin and transcription in response to chemical exposure lead to a “compensation” for underlying genetic-driven interindividual differences in the baseline chromatin and transcriptional state. This work represents an example of how chemical and environmental exposures can be evaluated to better understand gene-by-environment interactions, and it demonstrates the important role of chromatin response in transcriptomic changes and, potentially, in deleterious effects of exposure. https://doi.org/10.1289/EHP1937",2017 Oct 16,"['Chappell, Grace A.', 'Israel, Jennifer W.', 'Simon, Jeremy M.', 'Pott, Sebastian', 'Safi, Alexias', 'Eklund, Karl', 'Sexton, Kenneth G.', 'Bodnar, Wanda', 'Lieb, Jason D.', 'Crawford, Gregory E.', 'Rusyn, Ivan', 'Furey, Terrence S.']",Environ Health Perspect,,,False
fa4407c76e151d9a802720724d5604436d44e68b,PMC,"Multihospital Outbreak of a Middle East Respiratory Syndrome Coronavirus Deletion Variant, Jordan: A Molecular, Serologic, and Epidemiologic Investigation",http://dx.doi.org/10.1093/ofid/ofy095,PMC5965092,30294616,NO-CC CODE,"BACKGROUND: An outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Jordan in 2015 involved a variant virus that acquired distinctive deletions in the accessory open reading frames. We conducted a molecular and seroepidemiologic investigation to describe the deletion variant’s transmission patterns and epidemiology. METHODS: We reviewed epidemiologic and medical chart data and analyzed viral genome sequences from respiratory specimens of MERS-CoV cases. In early 2016, sera and standardized interviews were obtained from MERS-CoV cases and their contacts. Sera were evaluated by nucleocapsid and spike protein enzyme immunoassays and microneutralization. RESULTS: Among 16 cases, 11 (69%) had health care exposure and 5 (31%) were relatives of a known case; 13 (81%) were symptomatic, and 7 (44%) died. Genome sequencing of MERS-CoV from 13 cases revealed 3 transmissible deletions associated with clinical illness during the outbreak. Deletion variant sequences were epidemiologically clustered and linked to a common transmission chain. Interviews and sera were collected from 2 surviving cases, 23 household contacts, and 278 health care contacts; 1 (50%) case, 2 (9%) household contacts, and 3 (1%) health care contacts tested seropositive. CONCLUSIONS: The MERS-CoV deletion variants retained human-to-human transmissibility and caused clinical illness in infected persons despite accumulated mutations. Serology suggested limited transmission beyond that detected during the initial outbreak investigation.",2018 Apr 28,"['Payne, Daniel C', 'Biggs, Holly M', 'Al-Abdallat, Mohammad Mousa', 'Alqasrawi, Sultan', 'Lu, Xiaoyan', 'Abedi, Glen R', 'Haddadin, Aktham', 'Iblan, Ibrahim', 'Alsanouri, Tarek', 'Al Nsour, Mohannad', 'Sheikh Ali, Sami', 'Rha, Brian', 'Trivedi, Suvang U', 'Rasheed, Mohammed Ata Ur', 'Tamin, Azaibi', 'Lamers, Mart M', 'Haagmans, Bart L', 'Erdman, Dean D', 'Thornburg, Natalie J', 'Gerber, Susan I']",Open Forum Infect Dis,,,True
51015101bc15eff799980aa9a403bbb1e26ecace,PMC,"Multihospital Outbreak of a Middle East Respiratory Syndrome Coronavirus Deletion Variant, Jordan: A Molecular, Serologic, and Epidemiologic Investigation",http://dx.doi.org/10.1093/ofid/ofy095,PMC5965092,30294616,NO-CC CODE,"BACKGROUND: An outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Jordan in 2015 involved a variant virus that acquired distinctive deletions in the accessory open reading frames. We conducted a molecular and seroepidemiologic investigation to describe the deletion variant’s transmission patterns and epidemiology. METHODS: We reviewed epidemiologic and medical chart data and analyzed viral genome sequences from respiratory specimens of MERS-CoV cases. In early 2016, sera and standardized interviews were obtained from MERS-CoV cases and their contacts. Sera were evaluated by nucleocapsid and spike protein enzyme immunoassays and microneutralization. RESULTS: Among 16 cases, 11 (69%) had health care exposure and 5 (31%) were relatives of a known case; 13 (81%) were symptomatic, and 7 (44%) died. Genome sequencing of MERS-CoV from 13 cases revealed 3 transmissible deletions associated with clinical illness during the outbreak. Deletion variant sequences were epidemiologically clustered and linked to a common transmission chain. Interviews and sera were collected from 2 surviving cases, 23 household contacts, and 278 health care contacts; 1 (50%) case, 2 (9%) household contacts, and 3 (1%) health care contacts tested seropositive. CONCLUSIONS: The MERS-CoV deletion variants retained human-to-human transmissibility and caused clinical illness in infected persons despite accumulated mutations. Serology suggested limited transmission beyond that detected during the initial outbreak investigation.",2018 Apr 28,"['Payne, Daniel C', 'Biggs, Holly M', 'Al-Abdallat, Mohammad Mousa', 'Alqasrawi, Sultan', 'Lu, Xiaoyan', 'Abedi, Glen R', 'Haddadin, Aktham', 'Iblan, Ibrahim', 'Alsanouri, Tarek', 'Al Nsour, Mohannad', 'Sheikh Ali, Sami', 'Rha, Brian', 'Trivedi, Suvang U', 'Rasheed, Mohammed Ata Ur', 'Tamin, Azaibi', 'Lamers, Mart M', 'Haagmans, Bart L', 'Erdman, Dean D', 'Thornburg, Natalie J', 'Gerber, Susan I']",Open Forum Infect Dis,,,False
fb9affb11af777fb094923d12102fcc30d2f9e12,PMC,"Multihospital Outbreak of a Middle East Respiratory Syndrome Coronavirus Deletion Variant, Jordan: A Molecular, Serologic, and Epidemiologic Investigation",http://dx.doi.org/10.1093/ofid/ofy095,PMC5965092,30294616,NO-CC CODE,"BACKGROUND: An outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Jordan in 2015 involved a variant virus that acquired distinctive deletions in the accessory open reading frames. We conducted a molecular and seroepidemiologic investigation to describe the deletion variant’s transmission patterns and epidemiology. METHODS: We reviewed epidemiologic and medical chart data and analyzed viral genome sequences from respiratory specimens of MERS-CoV cases. In early 2016, sera and standardized interviews were obtained from MERS-CoV cases and their contacts. Sera were evaluated by nucleocapsid and spike protein enzyme immunoassays and microneutralization. RESULTS: Among 16 cases, 11 (69%) had health care exposure and 5 (31%) were relatives of a known case; 13 (81%) were symptomatic, and 7 (44%) died. Genome sequencing of MERS-CoV from 13 cases revealed 3 transmissible deletions associated with clinical illness during the outbreak. Deletion variant sequences were epidemiologically clustered and linked to a common transmission chain. Interviews and sera were collected from 2 surviving cases, 23 household contacts, and 278 health care contacts; 1 (50%) case, 2 (9%) household contacts, and 3 (1%) health care contacts tested seropositive. CONCLUSIONS: The MERS-CoV deletion variants retained human-to-human transmissibility and caused clinical illness in infected persons despite accumulated mutations. Serology suggested limited transmission beyond that detected during the initial outbreak investigation.",2018 Apr 28,"['Payne, Daniel C', 'Biggs, Holly M', 'Al-Abdallat, Mohammad Mousa', 'Alqasrawi, Sultan', 'Lu, Xiaoyan', 'Abedi, Glen R', 'Haddadin, Aktham', 'Iblan, Ibrahim', 'Alsanouri, Tarek', 'Al Nsour, Mohannad', 'Sheikh Ali, Sami', 'Rha, Brian', 'Trivedi, Suvang U', 'Rasheed, Mohammed Ata Ur', 'Tamin, Azaibi', 'Lamers, Mart M', 'Haagmans, Bart L', 'Erdman, Dean D', 'Thornburg, Natalie J', 'Gerber, Susan I']",Open Forum Infect Dis,,,False
1be0e0b85312fb2bf7e2f6914fb89dec82ff29d8,PMC,Mxra8 is a receptor for multiple arthritogenic alphaviruses,http://dx.doi.org/10.1038/s41586-018-0121-3,PMC5970976,29769725,NO-CC CODE,"Arthritogenic alphaviruses comprise a group of enveloped RNA viruses that are transmitted to humans by mosquitoes and cause debilitating acute and chronic musculoskeletal disease(1). The host factors required for alphavirus entry remain poorly characterized(2). Using a genome-wide CRISPR/Cas9-based screen, we identified the cell adhesion molecule Mxra8 as an entry mediator for multiple emerging arthritogenic alphaviruses including chikungunya (CHIKV), Ross River, Mayaro, and O’nyong nyong (ONNV) viruses. Gene editing of mouse Mxra8 or human MXRA8 resulted in reduced viral infection of cells, and reciprocally, ectopic expression resulted in increased infection. Mxra8 bound directly to CHIKV particles and enhanced virus attachment and internalization into cells. Consistent with these findings, Mxra8-Fc protein or anti-Mxra8 monoclonal antibodies blocked CHIKV infection in multiple cell types including primary human synovial fibroblasts, osteoblasts, chondrocytes, and skeletal muscle cells. Mutagenesis experiments suggest that Mxra8 binds to a surface-exposed region across the A and B domains of CHIKV E2, a speculated site of attachment. Finally, administration of Mxr8a-Fc protein or anti-Mxra8 blocking antibodies reduced CHIKV or ONNV infection and associated foot swelling in mice. Pharmacological targeting of Mxra8 could form a strategy for mitigating infection and disease by multiple arthritogenic alphaviruses.",2018 May 16,"['Zhang, Rong', 'Kim, Arthur S.', 'Fox, Julie M.', 'Nair, Sharmila', 'Basore, Katherine', 'Klimstra, William B.', 'Rimkunas, Rebecca', 'Fong, Rachel H.', 'Lin, Hueylie', 'Poddar, Subhajit', 'Crowe, James E.', 'Doranz, Benjamin J.', 'Fremont, Daved H.', 'Diamond, Michael S.']",Nature,,,True
e770da379851d0105fff14a6f509f152361d15e4,PMC,Mxra8 is a receptor for multiple arthritogenic alphaviruses,http://dx.doi.org/10.1038/s41586-018-0121-3,PMC5970976,29769725,NO-CC CODE,"Arthritogenic alphaviruses comprise a group of enveloped RNA viruses that are transmitted to humans by mosquitoes and cause debilitating acute and chronic musculoskeletal disease(1). The host factors required for alphavirus entry remain poorly characterized(2). Using a genome-wide CRISPR/Cas9-based screen, we identified the cell adhesion molecule Mxra8 as an entry mediator for multiple emerging arthritogenic alphaviruses including chikungunya (CHIKV), Ross River, Mayaro, and O’nyong nyong (ONNV) viruses. Gene editing of mouse Mxra8 or human MXRA8 resulted in reduced viral infection of cells, and reciprocally, ectopic expression resulted in increased infection. Mxra8 bound directly to CHIKV particles and enhanced virus attachment and internalization into cells. Consistent with these findings, Mxra8-Fc protein or anti-Mxra8 monoclonal antibodies blocked CHIKV infection in multiple cell types including primary human synovial fibroblasts, osteoblasts, chondrocytes, and skeletal muscle cells. Mutagenesis experiments suggest that Mxra8 binds to a surface-exposed region across the A and B domains of CHIKV E2, a speculated site of attachment. Finally, administration of Mxr8a-Fc protein or anti-Mxra8 blocking antibodies reduced CHIKV or ONNV infection and associated foot swelling in mice. Pharmacological targeting of Mxra8 could form a strategy for mitigating infection and disease by multiple arthritogenic alphaviruses.",2018 May 16,"['Zhang, Rong', 'Kim, Arthur S.', 'Fox, Julie M.', 'Nair, Sharmila', 'Basore, Katherine', 'Klimstra, William B.', 'Rimkunas, Rebecca', 'Fong, Rachel H.', 'Lin, Hueylie', 'Poddar, Subhajit', 'Crowe, James E.', 'Doranz, Benjamin J.', 'Fremont, Daved H.', 'Diamond, Michael S.']",Nature,,,True
9d02db669e8701c83186d7d3aae69da2f2cb3d34,PMC,In Vitro Bactericidal and Virucidal Efficacy of Povidone-Iodine Gargle/Mouthwash Against Respiratory and Oral Tract Pathogens,http://dx.doi.org/10.1007/s40121-018-0200-7,PMC5986684,29633177,NO-CC CODE,"INTRODUCTION: Recent virus epidemics and rising antibiotic resistance highlight the importance of hygiene measures to prevent and control outbreaks. We investigated the in vitro bactericidal and virucidal efficacy of povidone-iodine (PVP-I) 7% gargle/mouthwash at defined dilution against oral and respiratory tract pathogens. METHODS: PVP-I was tested against Klebsiella pneumoniae and Streptococcus pneumoniae according to bactericidal quantitative suspension test EN13727 and against severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses (SARS-CoV and MERS-CoV), rotavirus strain Wa and influenza virus A subtype H1N1 according to virucidal quantitative suspension test EN14476. PVP-I 7% gargle/mouthwash was diluted 1:30 with water to a concentration of 0.23% (the recommended concentration for “real-life” use in Japan) and tested at room temperature under clean conditions [0.3 g/l bovine serum albumin (BSA), viruses only] and dirty conditions (3.0 g/l BSA + 3.0 ml/l erythrocytes) as an interfering substance for defined contact times (minimum 15 s). Rotavirus was tested without protein load. A ≥ 5 log(10) (99.999%) decrease of bacteria and ≥ 4 log(10) (99.99%) reduction in viral titre represented effective bactericidal and virucidal activity, respectively, per European standards. RESULTS: PVP-I gargle/mouthwash diluted 1:30 (equivalent to a concentration of 0.23% PVP-I) showed effective bactericidal activity against Klebsiella pneumoniae and Streptococcus pneumoniae and rapidly inactivated SARS-CoV, MERS-CoV, influenza virus A (H1N1) and rotavirus after 15 s of exposure. CONCLUSION: PVP-I 7% gargle/mouthwash showed rapid bactericidal activity and virucidal efficacy in vitro at a concentration of 0.23% PVP-I and may provide a protective oropharyngeal hygiene measure for individuals at high risk of exposure to oral and respiratory pathogens. FUNDING: Mundipharma Research GmbH & Co. KG (MRG).",2018 Jun 9,"['Eggers, Maren', 'Koburger-Janssen, Torsten', 'Eickmann, Markus', 'Zorn, Juergen']",Infect Dis Ther,,,True
ec3ef2cdfe11f6f475f0c193fe3c4dfe1066f277,PMC,Bactericidal and Virucidal Activity of Povidone-Iodine and Chlorhexidine Gluconate Cleansers in an In Vivo Hand Hygiene Clinical Simulation Study,http://dx.doi.org/10.1007/s40121-018-0202-5,PMC5986686,29761329,NO-CC CODE,"INTRODUCTION: Standard in vitro and in vivo tests help demonstrate efficacy of hand hygiene products; however, there is no standard in vivo test method for viruses. We investigated the bactericidal and virucidal efficacy of povidone-iodine (PVP-I) 7.5% scalp and skin cleanser, chlorhexidine gluconate (CHG) 4% hand cleanser and the reference hand wash (soft soap) in 15 healthy volunteers following European Standard EN1499 (hygienic hand wash test method for bacteria), which was adapted for virucidal testing. METHODS: Separate test series were performed for bactericidal (Escherichia coli) and virucidal [murine norovirus (MNV)] testing. After pre-washing and artificial contamination of hands with test organisms, volunteers underwent testing with 3 and 5 mL of each product for contact times of 15, 30 and 60 s according to a Latin-square randomization. The number of test organisms released from fingertips into sampling fluids was assessed before and after hand washing and mean log(10) reduction factor (RF) was calculated. RFs (test-reference) were compared using a Wilcoxon–Wilcox multiple comparisons test per EN1499; efficacy was concluded if p ≤ 0.01. RESULTS: PVP-I 7.5% and CHG 4% cleansers both passed EN1499 requirements against E. coli, with statistically significantly greater (p ≤ 0.01) mean log(10) RFs compared with reference soft soap across all tests (PVP-I: 4.09–5.27; CHG: 4.12–5.22; soap: 2.75–3.11). The experimental design using EN1499 was applicable to testing with MNV as discriminatory and reproducible results were generated. Mean log(10) RFs of MNV were statistically significantly greater for PVP-I (1.57–2.57) compared with soft soap (1.24–1.62), while mean log(10) RFs with CHG (0.90–1.34) were lower than for soft soap across all tests. CONCLUSION: PVP-I 7.5% cleanser showed superior efficacy against MNV compared to soft soap and CHG 4% cleanser, while both PVP-I and CHG were superior to soft soap against E. coli. The experimental set-up may be applicable to future testing for antiviral hand washes. FUNDING: Mundipharma Manufacturing Pte Ltd. PLAIN LANGUAGE SUMMARY: Plain language summary available for this article.",2018 Jun 14,"['Eggers, Maren', 'Koburger-Janssen, Torsten', 'Ward, Lois S.', 'Newby, Craig', 'Müller, Stefan']",Infect Dis Ther,,,True
0f9a9bcd7f82dc2e386aa78be1dc311be95e314b,PMC,Multifunctional biophotonic nanostructures inspired by longtail glasswing butterfly for medical devices,http://dx.doi.org/10.1038/s41565-018-0111-5,PMC5992053,29713074,NO-CC CODE,"Numerous living organisms possess biophotonic nanostructures that provide coloration and other diverse functions for survival. While such structures have been actively studied and replicated in the laboratory, it remains unclear whether they can be used for biomedical applications. Here we show a transparent photonic nanostructure inspired by the longtail glasswing (Chorinea faunus) butterfly and demonstrate its use in intraocular pressure (IOP) sensors in vivo. We exploit the phase separation between two immiscible polymers (poly(methyl methacrylate) and polystyrene) to form nanostructured features on top of a Si(3)N(4) substrate. The membrane thus formed shows good angle-independent white light transmission, strong hydrophilicity and anti-biofouling properties that prevent adhesion of proteins, bacteria, and eukaryotic cells. We then developed a microscale implantable IOP sensor using our photonic membrane as an optomechanical sensing element. Finally, we performed in vivo testing on New Zealand white rabbits and show that our device reduces the mean IOP measurement variation compared to conventional rebound tonometry without signs of inflammation.",2018 Jun 30,"['Narasimhan, Vinayak', 'Siddique, Radwanul Hasan', 'Lee, Jeong Oen', 'Kumar, Shailabh', 'Ndjamen, Blaise', 'Du, Juan', 'Hong, Natalie', 'Sretavan, David', 'Choo, Hyuck']",Nat Nanotechnol,,,True
232d7b83c5e1ab61317eea4aa51cb6d264516b91,PMC,Multifunctional biophotonic nanostructures inspired by longtail glasswing butterfly for medical devices,http://dx.doi.org/10.1038/s41565-018-0111-5,PMC5992053,29713074,NO-CC CODE,"Numerous living organisms possess biophotonic nanostructures that provide coloration and other diverse functions for survival. While such structures have been actively studied and replicated in the laboratory, it remains unclear whether they can be used for biomedical applications. Here we show a transparent photonic nanostructure inspired by the longtail glasswing (Chorinea faunus) butterfly and demonstrate its use in intraocular pressure (IOP) sensors in vivo. We exploit the phase separation between two immiscible polymers (poly(methyl methacrylate) and polystyrene) to form nanostructured features on top of a Si(3)N(4) substrate. The membrane thus formed shows good angle-independent white light transmission, strong hydrophilicity and anti-biofouling properties that prevent adhesion of proteins, bacteria, and eukaryotic cells. We then developed a microscale implantable IOP sensor using our photonic membrane as an optomechanical sensing element. Finally, we performed in vivo testing on New Zealand white rabbits and show that our device reduces the mean IOP measurement variation compared to conventional rebound tonometry without signs of inflammation.",2018 Jun 30,"['Narasimhan, Vinayak', 'Siddique, Radwanul Hasan', 'Lee, Jeong Oen', 'Kumar, Shailabh', 'Ndjamen, Blaise', 'Du, Juan', 'Hong, Natalie', 'Sretavan, David', 'Choo, Hyuck']",Nat Nanotechnol,,,True
4818ee93570146cb14dcf0a88a8dec85f9127bae,PMC,Multifunctional biophotonic nanostructures inspired by longtail glasswing butterfly for medical devices,http://dx.doi.org/10.1038/s41565-018-0111-5,PMC5992053,29713074,NO-CC CODE,"Numerous living organisms possess biophotonic nanostructures that provide coloration and other diverse functions for survival. While such structures have been actively studied and replicated in the laboratory, it remains unclear whether they can be used for biomedical applications. Here we show a transparent photonic nanostructure inspired by the longtail glasswing (Chorinea faunus) butterfly and demonstrate its use in intraocular pressure (IOP) sensors in vivo. We exploit the phase separation between two immiscible polymers (poly(methyl methacrylate) and polystyrene) to form nanostructured features on top of a Si(3)N(4) substrate. The membrane thus formed shows good angle-independent white light transmission, strong hydrophilicity and anti-biofouling properties that prevent adhesion of proteins, bacteria, and eukaryotic cells. We then developed a microscale implantable IOP sensor using our photonic membrane as an optomechanical sensing element. Finally, we performed in vivo testing on New Zealand white rabbits and show that our device reduces the mean IOP measurement variation compared to conventional rebound tonometry without signs of inflammation.",2018 Jun 30,"['Narasimhan, Vinayak', 'Siddique, Radwanul Hasan', 'Lee, Jeong Oen', 'Kumar, Shailabh', 'Ndjamen, Blaise', 'Du, Juan', 'Hong, Natalie', 'Sretavan, David', 'Choo, Hyuck']",Nat Nanotechnol,,,False
fc8d3fb52dee4d49c606650486461f71f313d02c,PMC,Novel Parvovirus Related to Primate Bufaviruses in Dogs,http://dx.doi.org/10.3201/eid2406.171965,PMC6004837,29774829,NO-CC CODE,"A novel protoparvovirus species, related genetically to human bufaviruses, was identified in dogs with respiratory signs. The canine bufavirus was distantly related to the well-known canine protoparvovirus, canine parvovirus type 2, sharing low amino acid identities in the nonstructural protein 1 (40.6%) and in the capsid protein 1 (33.4%). By screening collections of fecal, nasal, and oropharyngeal samples obtained from juvenile dogs (<1 year of age), canine bufavirus DNA appeared as a common component of canine virome. The virus was common in the stool samples of dogs with or without enteric disease and in the nasal and oropharyngeal swab samples of dogs with respiratory signs. However, the virus was not detected in nasal and oropharyngeal swab samples from animals without clinical signs.",2018 Jun,"['Martella, Vito', 'Lanave, Gianvito', 'Mihalov-Kovács, Eszter', 'Marton, Szilvia', 'Varga-Kugler, Renáta', 'Kaszab, Eszter', 'Di Martino, Barbara', 'Camero, Michele', 'Decaro, Nicola', 'Buonavoglia, Canio', 'Bányai, Krisztián']",Emerg Infect Dis,,,True
1a817072b1314f9c052bcd6e7e4b37bf101642b6,PMC,Novel Parvovirus Related to Primate Bufaviruses in Dogs,http://dx.doi.org/10.3201/eid2406.171965,PMC6004837,29774829,NO-CC CODE,"A novel protoparvovirus species, related genetically to human bufaviruses, was identified in dogs with respiratory signs. The canine bufavirus was distantly related to the well-known canine protoparvovirus, canine parvovirus type 2, sharing low amino acid identities in the nonstructural protein 1 (40.6%) and in the capsid protein 1 (33.4%). By screening collections of fecal, nasal, and oropharyngeal samples obtained from juvenile dogs (<1 year of age), canine bufavirus DNA appeared as a common component of canine virome. The virus was common in the stool samples of dogs with or without enteric disease and in the nasal and oropharyngeal swab samples of dogs with respiratory signs. However, the virus was not detected in nasal and oropharyngeal swab samples from animals without clinical signs.",2018 Jun,"['Martella, Vito', 'Lanave, Gianvito', 'Mihalov-Kovács, Eszter', 'Marton, Szilvia', 'Varga-Kugler, Renáta', 'Kaszab, Eszter', 'Di Martino, Barbara', 'Camero, Michele', 'Decaro, Nicola', 'Buonavoglia, Canio', 'Bányai, Krisztián']",Emerg Infect Dis,,,False
3c6b88ab8a6694c82e04480184ae76dbe302c95d,PMC,"Infectious MERS-CoV Isolated From a Mildly Ill Patient, Saudi Arabia",http://dx.doi.org/10.1093/ofid/ofy111,PMC6016420,30294617,NO-CC CODE,"Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with a wide range of clinical presentations, from asymptomatic or mildly ill to severe respiratory illness including death. We describe isolation of infectious MERS-CoV from the upper respiratory tract of a mildly ill 27-year-old female in Saudi Arabia 15 days after illness onset.",2018 May 15,"['Al-Abdely, Hail M', 'Midgley, Claire M', 'Alkhamis, Abdulrahim M', 'Abedi, Glen R', 'Tamin, Azaibi', 'Binder, Alison M', 'Alanazi, Khalid', 'Lu, Xiaoyan', 'Abdalla, Osman', 'Sakthivel, Senthilkumar K', 'Mohammed, Mutaz', 'Queen, Krista', 'Algarni, Homoud S', 'Li, Yan', 'Trivedi, Suvang', 'Algwizani, Abdullah', 'Alhakeem, Raafat F', 'Thornburg, Natalie J', 'Tong, Suxiang', 'Ghazal, Sameeh S', 'Erdman, Dean D', 'Assiri, Abdullah M', 'Gerber, Susan I', 'Watson, John T']",Open Forum Infect Dis,,,True
b2893c753d19c6596ebcda65230f65b6935d18ba,PMC,Strengthening Global Public Health Surveillance through Data and Benefit Sharing,http://dx.doi.org/10.3201/eid2407.151830,PMC6038731,,NO-CC CODE,"Equitable sharing of public health surveillance data can help prevent or mitigate the effect of infectious diseases. Equitable data sharing includes working toward more equitable sharing of the public health benefits that data sharing brings and requires the engagement of those providing the data, those interpreting and using the data generated by others, those facilitating the data-sharing process, and those deriving and contributing to the benefit. An expert consultation conducted by Chatham House outlined 7 principles to encourage the process of equitable data sharing: 1) building trust; 2) articulating the value; 3) planning for data sharing; 4) achieving quality data; 5) understanding the legal context; 6) creating data-sharing agreements; and 7) monitoring and evaluation. Sharing of public health surveillance data is best done taking into account these principles, which will help to ensure data are shared optimally and ethically, while fulfilling stakeholder expectations and facilitating equitable distribution of benefits.",2018 Jul,"['Edelstein, Michael', 'Lee, Lisa M.', 'Herten-Crabb, Asha', 'Heymann, David L.', 'Harper, David R.']",Emerg Infect Dis,,,True
f121608401ad1aa6cce961c7ae97fd01fde0e1f6,PMC,Strengthening Global Public Health Surveillance through Data and Benefit Sharing,http://dx.doi.org/10.3201/eid2407.151830,PMC6038731,,NO-CC CODE,"Equitable sharing of public health surveillance data can help prevent or mitigate the effect of infectious diseases. Equitable data sharing includes working toward more equitable sharing of the public health benefits that data sharing brings and requires the engagement of those providing the data, those interpreting and using the data generated by others, those facilitating the data-sharing process, and those deriving and contributing to the benefit. An expert consultation conducted by Chatham House outlined 7 principles to encourage the process of equitable data sharing: 1) building trust; 2) articulating the value; 3) planning for data sharing; 4) achieving quality data; 5) understanding the legal context; 6) creating data-sharing agreements; and 7) monitoring and evaluation. Sharing of public health surveillance data is best done taking into account these principles, which will help to ensure data are shared optimally and ethically, while fulfilling stakeholder expectations and facilitating equitable distribution of benefits.",2018 Jul,"['Edelstein, Michael', 'Lee, Lisa M.', 'Herten-Crabb, Asha', 'Heymann, David L.', 'Harper, David R.']",Emerg Infect Dis,,,False
2038c68ce9ec2990a003c0ac0d5d87d8c072e102,PMC,"Molecular Epidemiology of Human Adenovirus–Associated Febrile Respiratory Illness in Soldiers, South Korea(1)",http://dx.doi.org/10.3201/eid2407.171222,PMC6038737,29912713,NO-CC CODE,"During January 2013–April 2014, we subjected nasopharyngeal specimens collected from patients with acute febrile respiratory illness in a military hospital to PCR testing to detect 12 respiratory viruses and sequence a partial hexon gene for human adenovirus (HAdV) molecular typing. We analyzed the epidemiologic characteristics of HAdV infections and compared clinical characteristics of HAdV types. Among the 305 patients with acute febrile respiratory illness, we detected respiratory viruses in 139 (45.6%) patients; HAdV was the most prevalent virus (69 cases). Of the 40 adenoviruses identified based on type, HAdV-55 (29 cases) was the most prevalent, followed by HAdV-4 (9 cases). HAdV-55 was common in patients with pneumonia (odds ratio 2.17; 95% CI 0.48–9.86) and hospitalized patients (odds ratio 5.21; 95% CI 1.06–25.50). In soldiers with HAdV infection in Korea, HAdV-55 was the most prevalent type and might be associated with severe clinical outcomes.",2018 Jul,"['Heo, Jung Yeon', 'Noh, Ji Yun', 'Jeong, Hye Won', 'Choe, Kang-Won', 'Song, Joon Young', 'Kim, Woo Joo', 'Cheong, Hee Jin']",Emerg Infect Dis,,,True
7abd3b3fc21fc2ff41ef6a23f988236f2065a045,PMC,"Progress in Vaccine-Preventable and Respiratory Infectious Diseases—First 10 Years of the CDC National Center for Immunization and Respiratory Diseases, 2006–2015",http://dx.doi.org/10.3201/eid2407.171699,PMC6038744,29916350,NO-CC CODE,"The need for closer linkages between scientific and programmatic areas focused on addressing vaccine-preventable and acute respiratory infections led to establishment of the National Center for Immunization and Respiratory Diseases (NCIRD) at the Centers for Disease Control and Prevention. During its first 10 years (2006–2015), NCIRD worked with partners to improve preparedness and response to pandemic influenza and other emergent respiratory infections, provide an evidence base for addition of 7 newly recommended vaccines, and modernize vaccine distribution. Clinical tools were developed for improved conversations with parents, which helped sustain childhood immunization as a social norm. Coverage increased for vaccines to protect adolescents against pertussis, meningococcal meningitis, and human papillomavirus–associated cancers. NCIRD programs supported outbreak response for new respiratory pathogens and oversaw response of the Centers for Disease Control and Prevention to the 2009 influenza A(H1N1) pandemic. Other national public health institutes might also find closer linkages between epidemiology, laboratory, and immunization programs useful.",2018 Jul,"['Schuchat, Anne', 'Anderson, Larry J.', 'Rodewald, Lance E.', 'Cox, Nancy J.', 'Hajjeh, Rana', 'Pallansch, Mark A.', 'Messonnier, Nancy E.', 'Jernigan, Daniel B.', 'Wharton, Melinda']",Emerg Infect Dis,,,True
9266f4d22d6f30e0f0aadc0ec45f5132ef029c56,PMC,"Progress in Vaccine-Preventable and Respiratory Infectious Diseases—First 10 Years of the CDC National Center for Immunization and Respiratory Diseases, 2006–2015",http://dx.doi.org/10.3201/eid2407.171699,PMC6038744,29916350,NO-CC CODE,"The need for closer linkages between scientific and programmatic areas focused on addressing vaccine-preventable and acute respiratory infections led to establishment of the National Center for Immunization and Respiratory Diseases (NCIRD) at the Centers for Disease Control and Prevention. During its first 10 years (2006–2015), NCIRD worked with partners to improve preparedness and response to pandemic influenza and other emergent respiratory infections, provide an evidence base for addition of 7 newly recommended vaccines, and modernize vaccine distribution. Clinical tools were developed for improved conversations with parents, which helped sustain childhood immunization as a social norm. Coverage increased for vaccines to protect adolescents against pertussis, meningococcal meningitis, and human papillomavirus–associated cancers. NCIRD programs supported outbreak response for new respiratory pathogens and oversaw response of the Centers for Disease Control and Prevention to the 2009 influenza A(H1N1) pandemic. Other national public health institutes might also find closer linkages between epidemiology, laboratory, and immunization programs useful.",2018 Jul,"['Schuchat, Anne', 'Anderson, Larry J.', 'Rodewald, Lance E.', 'Cox, Nancy J.', 'Hajjeh, Rana', 'Pallansch, Mark A.', 'Messonnier, Nancy E.', 'Jernigan, Daniel B.', 'Wharton, Melinda']",Emerg Infect Dis,,,False
361fcf9eb197bf251946ecf59341fcdb7a524a0f,PMC,"Spillover of Swine Coronaviruses, United States",http://dx.doi.org/10.3201/eid2407.172077,PMC6038755,29912697,NO-CC CODE,"Porcine epidemic diarrhea virus, a pathogen first detected in US domestic swine in 2013, has rapidly spilled over into feral swine populations. A better understanding of the factors associated with pathogen emergence is needed to better manage, and ultimately prevent, future spillover events from domestic to nondomestic animals.",2018 Jul,"['Bevins, Sarah N.', 'Lutman, Mark', 'Pedersen, Kerri', 'Barrett, Nicole', 'Gidlewski, Tom', 'Deliberto, Tom J.', 'Franklin, Alan B.']",Emerg Infect Dis,,,True
925366122df469b96d212da10c5be3e8cdcd385a,PMC,"Spillover of Swine Coronaviruses, United States",http://dx.doi.org/10.3201/eid2407.172077,PMC6038755,29912697,NO-CC CODE,"Porcine epidemic diarrhea virus, a pathogen first detected in US domestic swine in 2013, has rapidly spilled over into feral swine populations. A better understanding of the factors associated with pathogen emergence is needed to better manage, and ultimately prevent, future spillover events from domestic to nondomestic animals.",2018 Jul,"['Bevins, Sarah N.', 'Lutman, Mark', 'Pedersen, Kerri', 'Barrett, Nicole', 'Gidlewski, Tom', 'Deliberto, Tom J.', 'Franklin, Alan B.']",Emerg Infect Dis,,,True
96059507ee9c4acbd419bd96775c652eb4104332,PMC,"Detection of Respiratory Viruses in Deceased Persons, Spain, 2017",http://dx.doi.org/10.3201/eid2407.180162,PMC6038767,29912695,NO-CC CODE,"During the 2016–17 influenza season in Spain, we tested specimens from 57 elderly deceased persons for respiratory viruses. Influenza viruses were detected in 18% of the specimens and any respiratory virus in 47%. Only 7% of participants had received a diagnosis of infection with the detected virus before death.",2018 Jul,"['Navascués, Ana', 'Casado, Itziar', 'Pérez-García, Alejandra', 'Aguinaga, Aitziber', 'Martínez-Baz, Iván', 'Floristán, Yugo', 'Ezpeleta, Carmen', 'Castilla, Jesús']",Emerg Infect Dis,,,True
040b779f7721b3282ead3a55d3e5f25c565a8698,PMC,"Detection of Respiratory Viruses in Deceased Persons, Spain, 2017",http://dx.doi.org/10.3201/eid2407.180162,PMC6038767,29912695,NO-CC CODE,"During the 2016–17 influenza season in Spain, we tested specimens from 57 elderly deceased persons for respiratory viruses. Influenza viruses were detected in 18% of the specimens and any respiratory virus in 47%. Only 7% of participants had received a diagnosis of infection with the detected virus before death.",2018 Jul,"['Navascués, Ana', 'Casado, Itziar', 'Pérez-García, Alejandra', 'Aguinaga, Aitziber', 'Martínez-Baz, Iván', 'Floristán, Yugo', 'Ezpeleta, Carmen', 'Castilla, Jesús']",Emerg Infect Dis,,,False
e03a59f8c651cd120e4c06a6c4f6e87b20d5e2d4,PMC,Preparation of Aluminum Oxide-Coated Glass Slides for Glycan Microarrays,http://dx.doi.org/10.1021/acsomega.6b00143,PMC6044682,30023491,NO-CC CODE,"[Image: see text] In this study, we report the fabrication of aluminum oxide-coated glass (ACG) slides for the preparation of glycan microarrays. Pure aluminum (Al, 300 nm) was coated on glass slides via electron-beam vapor deposition polymerization (VDP), followed by anodization to form a thin layer (50–65 nm) of aluminum oxide (Al-oxide) on the surface. The ACG slides prepared this way provide a smooth surface for arraying sugars covalently via phosphonate formation with controlled density and spatial distance. To evaluate this array system, a mannose derivative of α-5-pentylphosphonic acid was used as a model for the optimization of covalent arraying based on the fluorescence response of the surface mannose interacting with concanavalin A (ConA) tagged with the fluorescence probe A488. The ACG slide was characterized using scanning electron microscopy, atomic force microscopy (AFM), and ellipsometry, and the sugar loading capacity, uniformity, and structural conformation were also characterized using AFM, a GenePix scanner, and a confocal microscope. This study has demonstrated that the glycan array prepared from the ACG slide is more homogeneous with better spatial control compared with the commonly used glycan array prepared from the N-hydroxysuccinimide-activated glass slide.",2016 Nov 3,"['Tseng, Susan\nYu', 'Cho, Wen-Hao', 'Su, James', 'Chang, Shih-Huang', 'Chiang, Donyau', 'Wu, Chung-Yi', 'Hsiao, Chien-Nan', 'Wong, Chi-Huey']",ACS Omega,,,True
3b3150852230121eab4302b9d423816d298b5419,PMC,Preparation of Aluminum Oxide-Coated Glass Slides for Glycan Microarrays,http://dx.doi.org/10.1021/acsomega.6b00143,PMC6044682,30023491,NO-CC CODE,"[Image: see text] In this study, we report the fabrication of aluminum oxide-coated glass (ACG) slides for the preparation of glycan microarrays. Pure aluminum (Al, 300 nm) was coated on glass slides via electron-beam vapor deposition polymerization (VDP), followed by anodization to form a thin layer (50–65 nm) of aluminum oxide (Al-oxide) on the surface. The ACG slides prepared this way provide a smooth surface for arraying sugars covalently via phosphonate formation with controlled density and spatial distance. To evaluate this array system, a mannose derivative of α-5-pentylphosphonic acid was used as a model for the optimization of covalent arraying based on the fluorescence response of the surface mannose interacting with concanavalin A (ConA) tagged with the fluorescence probe A488. The ACG slide was characterized using scanning electron microscopy, atomic force microscopy (AFM), and ellipsometry, and the sugar loading capacity, uniformity, and structural conformation were also characterized using AFM, a GenePix scanner, and a confocal microscope. This study has demonstrated that the glycan array prepared from the ACG slide is more homogeneous with better spatial control compared with the commonly used glycan array prepared from the N-hydroxysuccinimide-activated glass slide.",2016 Nov 3,"['Tseng, Susan\nYu', 'Cho, Wen-Hao', 'Su, James', 'Chang, Shih-Huang', 'Chiang, Donyau', 'Wu, Chung-Yi', 'Hsiao, Chien-Nan', 'Wong, Chi-Huey']",ACS Omega,,,False
e93d3778e75fa7201f27b9c93b541a16b8f4393a,PMC,Febrile seizures: an overview,http://dx.doi.org/10.7573/dic.212536,PMC6052913,30038660,NO-CC CODE,"BACKGROUND: Febrile seizures are the most common neurologic disorder in childhood. Physicians should be familiar with the proper evaluation and management of this common condition. OBJECTIVE: To provide an update on the current understanding, evaluation, and management of febrile seizures. METHODS: A PubMed search was completed in Clinical Queries using the key terms ‘febrile convulsions’ and ‘febrile seizures’. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. RESULTS: Febrile seizures, with a peak incidence between 12 and 18 months of age, likely result from a vulnerability of the developing central nervous system to the effects of fever, in combination with an underlying genetic predisposition and environmental factors. The majority of febrile seizures occur within 24 hours of the onset of the fever. Febrile seizures can be simple or complex. Clinical judgment based on variable presentations must direct the diagnostic studies which are usually not necessary in the majority of cases. A lumbar puncture should be considered in children younger than 12 months of age or with suspected meningitis. Children with complex febrile seizures are at risk of subsequent epilepsy. Approximately 30–40% of children with a febrile seizure will have a recurrence during early childhood. The prognosis is favorable as the condition is usually benign and self-limiting. Intervention to stop the seizure often is unnecessary. CONCLUSION: Continuous preventative antiepileptic therapy for the prevention of recurrent febrile seizures is not recommended. The use of intermittent anticonvulsant therapy is not routinely indicated. Antipyretics have no role in the prevention of febrile seizures.",2018 Jul 16,"['Leung, Alexander KC', 'Hon, Kam Lun', 'Leung, Theresa NH']",Drugs Context,,,True
55e21f37b34b47c33bdbec518825f78587906ddd,PMC,DETECTION OF NON-INFLUENZA VIRUSES IN ACUTE RESPIRATORY INFECTIONS IN CHILDREN UNDER FIVE-YEAR-OLD IN COTE D’IVOIRE (JANUARY – DECEMBER 2013),http://dx.doi.org/10.21010/ajid.v12i2.13,PMC6085743,30109291,NO-CC CODE,"BACKGROUND: Influenza sentinel surveillance in Cote d’Ivoire showed that 70% of Acute Respiratory Infections (ARI) cases remained without etiology. This work aims to describe the epidemiological, clinical, and virological pattern of ARI that tested negative for influenza virus, in children under five years old. MATERIALS AND METHODS: one thousand and fifty nine samples of patients presenting influenza Like Illness (ILI) or Severe Acute Respiratory Infections (SARI) symptoms were tested for other respiratory viruses using multiplex RT-PCR assays targeting 10 respiratory viruses. RESULTS: The following pathogens were detected as follows, hRV 31,92% (98/307), hRSV 24.4% (75/329), PIV 20.5% (63/307), HCoV 229E 12,05% (37/307), hMPV 6.2% (19/307), HCoVOC43 1.0% (3/307) and EnV 1.0% (3/307). Among the 1,059 specimens analyzed, 917 (86.6%) were ILI samples and 142 (23.4%) were SARI samples. The proportion of children infected with at least one virus was 29.8% (273/917) in ILI cases and 23.9% (34/142) in SARI cases. The most prevalent viruses, responsible for ILI cases were hRV with 35.89% (98/273) and hRSV in SARI cases with 41.2% (14/34) of cases. Among the 1,059 patients, only 22 (2.1%) children presented risk factors related to the severity of influenza virus infection. CONCLUSION: This study showed that respiratory viruses play an important role in the etiology of ARI in children. For a better understanding of the epidemiology of ARI and improved case management, it would be interesting in this context to expand the surveillance of influenza to other respiratory viruses.",2018 Jun 18,"['Kadjo, Herve A.', 'Adjogoua, Edgard', 'Dia, Ndongo', 'Adagba, Marius', 'Abdoulaye, Ouattara', 'Daniel, Saraka', 'Kouakou, Bertin', 'Ngolo, David C.', 'Coulibaly, Daouda', 'Ndahwouh, Talla Nzussouo', 'Dosso, Mireille']",Afr J Infect Dis,,,True
d931ca4a427c3ecfdc8608bc404a8a09c21d3bdc,PMC,"Event-Based Surveillance at Community and Healthcare Facilities, Vietnam, 2016–2017",http://dx.doi.org/10.3201/eid2409.171851,PMC6106426,30124198,NO-CC CODE,"Surveillance and outbreak reporting systems in Vietnam required improvements to function effectively as early warning and response systems. Accordingly, the Ministry of Health of Vietnam, in collaboration with the US Centers for Disease Control and Prevention, launched a pilot project in 2016 focusing on community and hospital event–based surveillance. The pilot was implemented in 4 of Vietnam’s 63 provinces. The pilot demonstrated that event-based surveillance resulted in early detection and reporting of outbreaks, improved collaboration between the healthcare facilities and preventive sectors of the ministry, and increased community participation in surveillance and reporting.",2018 Sep,"['Clara, Alexey', 'Do, Trang T.', 'Dao, Anh T.P.', 'Tran, Phu D.', 'Dang, Tan Q.', 'Tran, Quang D.', 'Ngu, Nghia D.', 'Ngo, Tu H.', 'Phan, Hung C.', 'Nguyen, Thuy T.P.', 'Lai, Anh T.', 'Nguyen, Dung T.', 'Nguyen, My K.', 'Nguyen, Hieu T.M.', 'Becknell, Steven', 'Bernadotte, Christina', 'Nguyen, Huyen T.', 'Nguyen, Quoc C.', 'Mounts, Anthony W.', 'Balajee, S. Arunmozhi']",Emerg Infect Dis,,,True
f33262c1f98b13eb814eb7359521fd4394f48ce0,PMC,World Health Organization Methodology to Prioritize Emerging Infectious Diseases in Need of Research and Development,http://dx.doi.org/10.3201/eid2409.171427,PMC6106429,30124424,NO-CC CODE,"The World Health Organization R&D Blueprint aims to accelerate the availability of medical technologies during epidemics by focusing on a list of prioritized emerging diseases for which medical countermeasures are insufficient or nonexistent. The prioritization process has 3 components: a Delphi process to narrow down a list of potential priority diseases, a multicriteria decision analysis to rank the short list of diseases, and a final Delphi round to arrive at a final list of 10 diseases. A group of international experts applied this process in January 2017, resulting in a list of 10 priority diseases. The robustness of the list was tested by performing a sensitivity analysis. The new process corrected major shortcomings in the pre–R&D Blueprint approach to disease prioritization and increased confidence in the results.",2018 Sep,"['Mehand, Massinissa Si', 'Millett, Piers', 'Al-Shorbaji, Farah', 'Roth, Cathy', 'Kieny, Marie Paule', 'Murgue, Bernadette']",Emerg Infect Dis,,,True
8c8ebf34d7a88d9717419e6bb9a3c3c2e4e02ff9,PMC,World Health Organization Methodology to Prioritize Emerging Infectious Diseases in Need of Research and Development,http://dx.doi.org/10.3201/eid2409.171427,PMC6106429,30124424,NO-CC CODE,"The World Health Organization R&D Blueprint aims to accelerate the availability of medical technologies during epidemics by focusing on a list of prioritized emerging diseases for which medical countermeasures are insufficient or nonexistent. The prioritization process has 3 components: a Delphi process to narrow down a list of potential priority diseases, a multicriteria decision analysis to rank the short list of diseases, and a final Delphi round to arrive at a final list of 10 diseases. A group of international experts applied this process in January 2017, resulting in a list of 10 priority diseases. The robustness of the list was tested by performing a sensitivity analysis. The new process corrected major shortcomings in the pre–R&D Blueprint approach to disease prioritization and increased confidence in the results.",2018 Sep,"['Mehand, Massinissa Si', 'Millett, Piers', 'Al-Shorbaji, Farah', 'Roth, Cathy', 'Kieny, Marie Paule', 'Murgue, Bernadette']",Emerg Infect Dis,,,True
573493d746ec76df2e1be09d7a51c100de5267b0,PMC,World Health Organization Methodology to Prioritize Emerging Infectious Diseases in Need of Research and Development,http://dx.doi.org/10.3201/eid2409.171427,PMC6106429,30124424,NO-CC CODE,"The World Health Organization R&D Blueprint aims to accelerate the availability of medical technologies during epidemics by focusing on a list of prioritized emerging diseases for which medical countermeasures are insufficient or nonexistent. The prioritization process has 3 components: a Delphi process to narrow down a list of potential priority diseases, a multicriteria decision analysis to rank the short list of diseases, and a final Delphi round to arrive at a final list of 10 diseases. A group of international experts applied this process in January 2017, resulting in a list of 10 priority diseases. The robustness of the list was tested by performing a sensitivity analysis. The new process corrected major shortcomings in the pre–R&D Blueprint approach to disease prioritization and increased confidence in the results.",2018 Sep,"['Mehand, Massinissa Si', 'Millett, Piers', 'Al-Shorbaji, Farah', 'Roth, Cathy', 'Kieny, Marie Paule', 'Murgue, Bernadette']",Emerg Infect Dis,,,True
fbad43ecd53034861cf23c877f45ee6265bfc386,PMC,World Health Organization Methodology to Prioritize Emerging Infectious Diseases in Need of Research and Development,http://dx.doi.org/10.3201/eid2409.171427,PMC6106429,30124424,NO-CC CODE,"The World Health Organization R&D Blueprint aims to accelerate the availability of medical technologies during epidemics by focusing on a list of prioritized emerging diseases for which medical countermeasures are insufficient or nonexistent. The prioritization process has 3 components: a Delphi process to narrow down a list of potential priority diseases, a multicriteria decision analysis to rank the short list of diseases, and a final Delphi round to arrive at a final list of 10 diseases. A group of international experts applied this process in January 2017, resulting in a list of 10 priority diseases. The robustness of the list was tested by performing a sensitivity analysis. The new process corrected major shortcomings in the pre–R&D Blueprint approach to disease prioritization and increased confidence in the results.",2018 Sep,"['Mehand, Massinissa Si', 'Millett, Piers', 'Al-Shorbaji, Farah', 'Roth, Cathy', 'Kieny, Marie Paule', 'Murgue, Bernadette']",Emerg Infect Dis,,,True
b9e13e3c31f4361833a9c3ac5647d3f3d3aea670,PMC,World Health Organization Methodology to Prioritize Emerging Infectious Diseases in Need of Research and Development,http://dx.doi.org/10.3201/eid2409.171427,PMC6106429,30124424,NO-CC CODE,"The World Health Organization R&D Blueprint aims to accelerate the availability of medical technologies during epidemics by focusing on a list of prioritized emerging diseases for which medical countermeasures are insufficient or nonexistent. The prioritization process has 3 components: a Delphi process to narrow down a list of potential priority diseases, a multicriteria decision analysis to rank the short list of diseases, and a final Delphi round to arrive at a final list of 10 diseases. A group of international experts applied this process in January 2017, resulting in a list of 10 priority diseases. The robustness of the list was tested by performing a sensitivity analysis. The new process corrected major shortcomings in the pre–R&D Blueprint approach to disease prioritization and increased confidence in the results.",2018 Sep,"['Mehand, Massinissa Si', 'Millett, Piers', 'Al-Shorbaji, Farah', 'Roth, Cathy', 'Kieny, Marie Paule', 'Murgue, Bernadette']",Emerg Infect Dis,,,True
a7b821c27f0e48460b838afa289ab348f672b5aa,PMC,World Health Organization Methodology to Prioritize Emerging Infectious Diseases in Need of Research and Development,http://dx.doi.org/10.3201/eid2409.171427,PMC6106429,30124424,NO-CC CODE,"The World Health Organization R&D Blueprint aims to accelerate the availability of medical technologies during epidemics by focusing on a list of prioritized emerging diseases for which medical countermeasures are insufficient or nonexistent. The prioritization process has 3 components: a Delphi process to narrow down a list of potential priority diseases, a multicriteria decision analysis to rank the short list of diseases, and a final Delphi round to arrive at a final list of 10 diseases. A group of international experts applied this process in January 2017, resulting in a list of 10 priority diseases. The robustness of the list was tested by performing a sensitivity analysis. The new process corrected major shortcomings in the pre–R&D Blueprint approach to disease prioritization and increased confidence in the results.",2018 Sep,"['Mehand, Massinissa Si', 'Millett, Piers', 'Al-Shorbaji, Farah', 'Roth, Cathy', 'Kieny, Marie Paule', 'Murgue, Bernadette']",Emerg Infect Dis,,,True
e37b1c311425bec4d902ba5f26d3d787409c5451,PMC,World Health Organization Methodology to Prioritize Emerging Infectious Diseases in Need of Research and Development,http://dx.doi.org/10.3201/eid2409.171427,PMC6106429,30124424,NO-CC CODE,"The World Health Organization R&D Blueprint aims to accelerate the availability of medical technologies during epidemics by focusing on a list of prioritized emerging diseases for which medical countermeasures are insufficient or nonexistent. The prioritization process has 3 components: a Delphi process to narrow down a list of potential priority diseases, a multicriteria decision analysis to rank the short list of diseases, and a final Delphi round to arrive at a final list of 10 diseases. A group of international experts applied this process in January 2017, resulting in a list of 10 priority diseases. The robustness of the list was tested by performing a sensitivity analysis. The new process corrected major shortcomings in the pre–R&D Blueprint approach to disease prioritization and increased confidence in the results.",2018 Sep,"['Mehand, Massinissa Si', 'Millett, Piers', 'Al-Shorbaji, Farah', 'Roth, Cathy', 'Kieny, Marie Paule', 'Murgue, Bernadette']",Emerg Infect Dis,,,False
b4415bd2dea3b83efaf8cd097c8911614814ef6e,PMC,Travelers’ Actual and Subjective Knowledge about Risk for Ebola Virus Disease,http://dx.doi.org/10.3201/eid2409.171343,PMC6106432,30124406,NO-CC CODE,"To determine travelers’ actual and subjective knowledge about risk for Ebola virus disease, we surveyed travelers from France. Actual knowledge did not prevent irrational perceptions or promote safe behavior. Rather, readiness to adopt protective behavior depended on subjective knowledge and overconfidence in ability to self-protect.",2018 Sep,"['Régner, Isabelle', 'Ianos, Oana Elena', 'Shajrawi, Loucy', 'Brouqui, Philippe', 'Gautret, Philippe']",Emerg Infect Dis,,,True
e05de9e9983b9e4ee063afa20cbe46a38243b9d1,PMC,Travelers’ Actual and Subjective Knowledge about Risk for Ebola Virus Disease,http://dx.doi.org/10.3201/eid2409.171343,PMC6106432,30124406,NO-CC CODE,"To determine travelers’ actual and subjective knowledge about risk for Ebola virus disease, we surveyed travelers from France. Actual knowledge did not prevent irrational perceptions or promote safe behavior. Rather, readiness to adopt protective behavior depended on subjective knowledge and overconfidence in ability to self-protect.",2018 Sep,"['Régner, Isabelle', 'Ianos, Oana Elena', 'Shajrawi, Loucy', 'Brouqui, Philippe', 'Gautret, Philippe']",Emerg Infect Dis,,,True
7478fba4c601f5330f85e76a8be0182effdb9ae5,PMC,Emerging Infectious Literatures and the Zombie Condition,http://dx.doi.org/10.3201/eid2409.170658,PMC6106442,,NO-CC CODE,"The book club format has enabled expert and nonexpert exploration of infection and epidemiology as encountered in popular literature. This exploration reveals that fiction focusing on apocalyptic disease often uses the zombie as embodiment of infection, as well as an exemplar of current knowledge on emerging disease.",2018 Sep,"['Verran, Joanna', 'Reyes, Xavier Aldana']",Emerg Infect Dis,,,True
5bc64dd87cf5c7502eb06d534d15d718c6c02214,PMC,"Influenza C Virus in Cattle with Respiratory Disease, United States, 2016–2018",http://dx.doi.org/10.3201/eid2410.180589,PMC6154146,30226175,NO-CC CODE,We identified influenza C virus (ICV) in samples from US cattle with bovine respiratory disease through real-time PCR testing and sequencing. Bovine ICV isolates had high nucleotide identities (≈98%) with each other and were closely related to human ICV strains (≈95%). Further research is needed to determine bovine ICV’s zoonotic potential.,2018 Oct,"['Zhang, Hewei', 'Porter, Elizabeth', 'Lohman, Molly', 'Lu, Nanyan', 'Peddireddi, Lalitha', 'Hanzlicek, Gregg', 'Marthaler, Douglas', 'Liu, Xuming', 'Bai, Jianfa']",Emerg Infect Dis,,,True
d58be1bc0e9893f61c4fb1f2fa632821ecfac98d,PMC,"Influenza C Virus in Cattle with Respiratory Disease, United States, 2016–2018",http://dx.doi.org/10.3201/eid2410.180589,PMC6154146,30226175,NO-CC CODE,We identified influenza C virus (ICV) in samples from US cattle with bovine respiratory disease through real-time PCR testing and sequencing. Bovine ICV isolates had high nucleotide identities (≈98%) with each other and were closely related to human ICV strains (≈95%). Further research is needed to determine bovine ICV’s zoonotic potential.,2018 Oct,"['Zhang, Hewei', 'Porter, Elizabeth', 'Lohman, Molly', 'Lu, Nanyan', 'Peddireddi, Lalitha', 'Hanzlicek, Gregg', 'Marthaler, Douglas', 'Liu, Xuming', 'Bai, Jianfa']",Emerg Infect Dis,,,True
10ec2c11f19caa55906670f42b14fa28ded3a926,PMC,Severe Respiratory Illness Outbreak Associated with Human Coronavirus NL63 in a Long-Term Care Facility,http://dx.doi.org/10.3201/eid2410.180862,PMC6154147,30226169,NO-CC CODE,"We describe an outbreak of severe respiratory illness associated with human coronavirus NL63 in a long-term care facility in Louisiana in November 2017. Six of 20 case-patients were hospitalized with pneumonia, and 3 of 20 died. Clinicians should consider human coronavirus NL63 for patients in similar settings with respiratory disease.",2018 Oct,"['Hand, Julie', 'Rose, Erica Billig', 'Salinas, Andrea', 'Lu, Xiaoyan', 'Sakthivel, Senthilkumar K.', 'Schneider, Eileen', 'Watson, John T.']",Emerg Infect Dis,,,True
9fa81d8d9b302402c54cefce4885df1317658c13,PMC,"Genome Sequences of Rhinovirus Genotype C56 Detected in Three Patients with Acute Respiratory Illness, California, 2016 to 2017",http://dx.doi.org/10.1128/MRA.00982-18,PMC6180327,30320303,NO-CC CODE,"We report here two genome sequences of a newly designated rhinovirus genotype, RV-C56, which were obtained from respiratory specimens of three patients with acute respiratory illness in 2016 and 2017. To our knowledge, these sequences represent the first near-complete genomes for RV-C56 strains.",2018 Aug 23,"['Pan, Chao-Yang', 'Yagi, Shigeo', 'Padilla, Tasha', 'Ng, Terry Fei Fan', 'Marine, Rachel L.', 'Nix, W. Allan', 'Wadford, Debra A.']",Microbiol Resour Announc,,,True
f9ba45c34f390b5c7d0579b641303de39860a329,PMC,Respiratory Viruses and Atypical Bacteria Co-Infection in Children with Acute Respiratory Infection,http://dx.doi.org/10.3889/oamjms.2018.332,PMC6182545,30337970,NO-CC CODE,"BACKGROUND: Acute respiratory infections (ARI) are one of the prevalent pediatric diseases. Coinfections of respiratory viruses and atypical bacterial respiratory pathogens are common. AIM: This study aimed to determine the prevalence of co-infection between respiratory pathogens including viruses, bacteria and atypical bacteria in a sample of Egyptian children presenting with symptoms of acute respiratory tract infection. METHODS: This one-year prospective cohort study conducted in Abo El Rish Pediatric Hospital, Cairo University over one year included children presenting with symptoms of acute respiratory infection. Enrolled children were subjected to nasopharyngeal swabs or throat swabs and then processed to detect viral, bacterial and atypical bacterial causative agents by culture), retrotranscription polymerase, Monoplex polymerase chain reaction (PCR) and Multiplex PCR. RESULTS: Viral etiological agents were detected in 20 cases (20.8%), while 76 patients (79.2%) had no definite viral aetiology. The most abundant virus detected was Rhinovirus in 36 (27.3%), followed by 21 (15.9%) were positive for RSV, 12 (9.1%) were positive for HMPV, 6 (4.5%) were positive for adenovirus and 3 (2.3%) were positive for influenza B. For Atypical bacterial causes Mycoplasma were positive for 9 (6.8%) cases and one case was positive for Bordetella parapertussis. Viral and atypical bacteria Co infection were detected in 14 (10.6%) of cases. CONCLUSION: These results suggest that coinfection with bacteria or atypical bacteria in children with acute respiratory tract infection is common and this co-infection can induce serious illness. The multiplex reverse-transcriptase polymerase chain reaction should become an essential tool for epidemiological studies and can fill the gap between clinical presentation and definitive diagnosis.",2018 Aug 23,"['Baroudy, Nevine R. El', 'Refay, Amira S. El', 'Hamid, Tamer A. Abdel', 'Hassan, Dina M.', 'Soliman, May S.', 'Sherif, Lobna']",Open Access Maced J Med Sci,,,True
ad512ced9c178a408dba4c56b96034fc7e894678,PMC,The Power of Consumer Activism and the Value of Public Health Immunization Registries in a Pandemic: Preparedness for Emerging Diseases and Today’s Outbreaks,http://dx.doi.org/10.5210/ojphi.v10i2.9147,PMC6194094,30349621,NO-CC CODE,"Public Health immunization registries and the immunization ecosystem have evolved over the past two decades to become significant population health data assets. Clinical providers and pharmacists are reporting the immunizations given to their patients to public health registries in 49 states and all territories, creating consolidated immunization event patient records. Most of these immunization events are reported through the provider’s Electronic Health Record system (EHR), Pharmacy Management System (PMS), online, or through data uploads. Meaningful Use and health data standards (HL7) became the drivers that accelerated reporting to immunization registries and significantly improved the quantity and quality of the data. The infrastructure supporting the Immunization Ecosystem (IE) has enabled real-time compliance reporting and, more importantly, real-time patient queries. The provider community now has online access to a patient’s immunization history in over three quarters of the states, and growing. This access includes a forecast of the patient’s immunization gaps provided by public health decision support tools based upon the most recent ACIP recommendations. This is creating an opportunity for the provider and the patient to work together to reduce their risk of suffering a vaccine-preventable disease. This IE and the data in an Immunization Information System (IIS) are especially useful as pharmacies expand their immunization practices and create opportunities to reduce the adolescent and adult immunization gaps. In a few states, this provider-public health ecosystem has begun to extend to individuals by allowing them to access the IIS online through the use of MyIR. MyIR provides them with the electronic version of their immunization ""yellow cards,"" recommendations for immunizations due, and the ability to print official certificates. This emerging consumer engagement creates opportunities to empower individuals to be more proactive in their family’s health care. This paper builds upon early experiments to empower individuals in this ecosystem by leveraging the value of these public health data assets and trusted communications, illustrating the possibilities for engaging consumers to support reducing the impact of emerging diseases, outbreaks and the next pandemic. This paper will suggest the value of the IE and the role individuals can play within their own social networks to advance public health efforts to manage disease events. In turn, this social mission would encourage consumers to be more proactive in managing their own healthcare.",2018 Sep 21,"['Popovich, Michael L.', None, 'Watkins, Todd', None, 'Kudia, Ousswa']",Online J Public Health Inform,,,True
23e73664ec4374d13d3a5243006bec6f30f5cda4,PMC,Evaluation of Data Exchange Process for Interoperability and Impact on Electronic Laboratory Reporting Quality to a State Public Health Agency,http://dx.doi.org/10.5210/ojphi.v10i2.9317,PMC6194099,30349622,NO-CC CODE,"BACKGROUND: Past and present national initiatives advocate for electronic exchange of health data and emphasize interoperability. The critical role of public health in the context of disease surveillance was recognized with recommendations for electronic laboratory reporting (ELR). Many public health agencies have seen a trend towards centralization of information technology services which adds another layer of complexity to interoperability efforts. OBJECTIVES: The study objective was to understand the process of data exchange and its impact on the quality of data being transmitted in the context of electronic laboratory reporting to public health. This was conducted in context of Minnesota Electronic Disease Surveillance System (MEDSS), the public health information system for supporting infectious disease surveillance in Minnesota. Data Quality (DQ) dimensions by Strong et al., was chosen as the guiding framework for evaluation. METHODS: The process of assessing data exchange for electronic lab reporting and its impact was a mixed methods approach with qualitative data obtained through expert discussions and quantitative data obtained from queries of the MEDSS system. Interviews were conducted in an open-ended format from November 2017 through February 2018. Based on these discussions, two high level categories of data exchange process which could impact data quality were identified: onboarding for electronic lab reporting and internal data exchange routing. This in turn comprised of ten critical steps and its impact on quality of data was identified through expert input. This was followed by analysis of data in MEDSS by various criteria identified by the informatics team. RESULTS: All DQ metrics (Intrinsic DQ, Contextual DQ, Representational DQ, and Accessibility DQ) were impacted in the data exchange process with varying influence on DQ dimensions. Some errors such as improper mapping in electronic health records (EHRs) and laboratory information systems had a cascading effect and can pass through technical filters and go undetected till use of data by epidemiologists. Some DQ dimensions such as accuracy, relevancy, value-added data and interpretability are more dependent on users at either end of the data exchange spectrum, the relevant clinical groups and the public health program professionals. The study revealed that data quality is dynamic and on-going oversight is a combined effort by MEDSS Informatics team and review by technical and public health program professionals. CONCLUSION: With increasing electronic reporting to public health, there is a need to understand the current processes for electronic exchange and their impact on quality of data. This study focused on electronic laboratory reporting to public health and analyzed both onboarding and internal data exchange processes. Insights gathered from this research can be applied to other public health reporting currently (e.g. immunizations) and will be valuable in planning for electronic case reporting in near future.",2018 Sep 21,"['Rajamani, Sripriya', 'Kayser, Ann', 'Emerson, Emily', 'Solarz, Sarah']",Online J Public Health Inform,,,True
529511c62c786dab397b5a3ab3859961a74c8cf8,PMC,A CRISPR screen identifies IFI6 as an ER-resident interferon effector that blocks flavivirus replication,http://dx.doi.org/10.1038/s41564-018-0244-1,PMC6202210,30224801,NO-CC CODE,,2018 Nov 17,"['Richardson, R. Blake', 'Ohlson, Maikke B.', 'Eitson, Jennifer L.', 'Kumar, Ashwani', 'McDougal, Matthew B.', 'Boys, Ian N.', 'Mar, Katrina B.', 'De La Cruz Rivera, Pamela', 'Douglas, Connor', 'Konopka, Genevieve', 'Xing, Chao', 'Schoggins, John W.']",Nat Microbiol,,,True
a5c784a31fe00d8790017dae8081e5000e1323fa,PMC,A CRISPR screen identifies IFI6 as an ER-resident interferon effector that blocks flavivirus replication,http://dx.doi.org/10.1038/s41564-018-0244-1,PMC6202210,30224801,NO-CC CODE,,2018 Nov 17,"['Richardson, R. Blake', 'Ohlson, Maikke B.', 'Eitson, Jennifer L.', 'Kumar, Ashwani', 'McDougal, Matthew B.', 'Boys, Ian N.', 'Mar, Katrina B.', 'De La Cruz Rivera, Pamela', 'Douglas, Connor', 'Konopka, Genevieve', 'Xing, Chao', 'Schoggins, John W.']",Nat Microbiol,,,True
cef7f5261816757a676b571a44aad8723b06821f,PMC,A CRISPR screen identifies IFI6 as an ER-resident interferon effector that blocks flavivirus replication,http://dx.doi.org/10.1038/s41564-018-0244-1,PMC6202210,30224801,NO-CC CODE,,2018 Nov 17,"['Richardson, R. Blake', 'Ohlson, Maikke B.', 'Eitson, Jennifer L.', 'Kumar, Ashwani', 'McDougal, Matthew B.', 'Boys, Ian N.', 'Mar, Katrina B.', 'De La Cruz Rivera, Pamela', 'Douglas, Connor', 'Konopka, Genevieve', 'Xing, Chao', 'Schoggins, John W.']",Nat Microbiol,,,False
312fd0cbdcfa35842d1a45ea9db93a90e1c4a287,PMC,Pneumococcal Pneumonia---Risky Business,http://dx.doi.org/10.1007/BF03399446,PMC6205671,,NO-CC CODE,,2014 Dec 1,,Pneumonia (Nathan),,,False
27274e02683a0348194933d6f5669741346b7113,PMC,Pandemic influenza A (H1N1) during winter influenza season in the southern hemisphere,http://dx.doi.org/10.1111/j.1750-2659.2010.00147.x,PMC6225867,20629772,NO-CC CODE,"Please cite this paper as: Hsieh Ying‐Hen. (2010) Pandemic influenza A (H1N1) during winter influenza season in the southern hemisphere. Influenza and Other Respiratory Viruses 4(4), 187–197. Background  Countries in the southern hemisphere experienced sizable epidemics of pandemic influenza H1N1 in their winter season during May–August, 2009. Methods  We make use of the Richards model to fit the publicly available epidemic data (confirmed cases, hospitalizations, and deaths) of six southern hemisphere countries (Argentina, Brazil, Chile, Australia, New Zealand, and South Africa) to draw useful conclusions, in terms of its reproduction numbers and outbreak turning points, regarding the new pH1N1 virus in a typical winter influenza season. Results  The estimates for the reproduction numbers of these six countries range from a high of 1·53 (95% CI: 1·22, 1·84) for confirmed case data of Brazil to a low of 1·16 (1·09, 1·22) for pH1N1 hospitalizations in Australia. For each country, model fits using confirmed cases, hospitalizations, or deaths data always yield similar estimates for the reproduction number. Moreover, the turning points for these closely related outbreak indicators always follow the correct chronological order, i.e., case–hospitalization–death, whenever two or more of these three indicators are available. Conclusions  The results suggest that the winter pH1N1 outbreaks in the southern hemisphere were similar to the earlier spring and later winter outbreaks in North America in its severity and transmissibility, as indicated by the reproduction numbers. Therefore, the current strain has not become more severe or transmissible while circulating around the globe in 2009 as some experts had cautioned. The results will be useful for global preparedness planning of possible tertiary waves of pH1N1 infections in the fall/winter of 2010.",2010 Jul 8,"Hsieh, Ying‐Hen",Influenza Other Respir Viruses,,,True
c50308992db0a3aac3f2624668e5708d221ba230,PMC,Inflammation induced by influenza virus impairs human innate immune control of pneumococcus,http://dx.doi.org/10.1038/s41590-018-0231-y,PMC6241853,30374129,NO-CC CODE,"Colonization of the upper respiratory tract by pneumococcus is important both as a determinant of disease and for transmission into the population. The immunological mechanisms that contain pneumococcus during colonization are well studied in mice but remain unclear in humans. Loss of this control of pneumococcus following infection with influenza virus is associated with secondary bacterial pneumonia. We used a human challenge model with type 6B pneumococcus to show that acquisition of pneumococcus induced early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function was associated with the clearance of pneumococcus. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate immune function and altered genome-wide nasal gene responses to the carriage of pneumococcus. Levels of the cytokine CXCL10, promoted by viral infection, at the time pneumococcus was encountered were positively associated with bacterial load.",2018 Dec 29,"['Jochems, Simon P.', 'Marcon, Fernando', 'Carniel, Beatriz F.', 'Holloway, Mark', 'Mitsi, Elena', 'Smith, Emma', 'Gritzfeld, Jenna F.', 'Solórzano, Carla', 'Reiné, Jesús', 'Pojar, Sherin', 'Nikolaou, Elissavet', 'German, Esther L.', 'Hyder-Wright, Angie', 'Hill, Helen', 'Hales, Caz', 'de Steenhuijsen Piters, Wouter A.A', 'Bogaert, Debby', 'Adler, Hugh', 'Zaidi, Seher', 'Connor, Victoria', 'Gordon, Stephen B.', 'Rylance, Jamie', 'Nakaya, Helder I.', 'Ferreira, Daniela M.']",Nat Immunol,,,True
449a4b7b716fca8b205ee4ede84769419f15ed32,PMC,Inflammation induced by influenza virus impairs human innate immune control of pneumococcus,http://dx.doi.org/10.1038/s41590-018-0231-y,PMC6241853,30374129,NO-CC CODE,"Colonization of the upper respiratory tract by pneumococcus is important both as a determinant of disease and for transmission into the population. The immunological mechanisms that contain pneumococcus during colonization are well studied in mice but remain unclear in humans. Loss of this control of pneumococcus following infection with influenza virus is associated with secondary bacterial pneumonia. We used a human challenge model with type 6B pneumococcus to show that acquisition of pneumococcus induced early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function was associated with the clearance of pneumococcus. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate immune function and altered genome-wide nasal gene responses to the carriage of pneumococcus. Levels of the cytokine CXCL10, promoted by viral infection, at the time pneumococcus was encountered were positively associated with bacterial load.",2018 Dec 29,"['Jochems, Simon P.', 'Marcon, Fernando', 'Carniel, Beatriz F.', 'Holloway, Mark', 'Mitsi, Elena', 'Smith, Emma', 'Gritzfeld, Jenna F.', 'Solórzano, Carla', 'Reiné, Jesús', 'Pojar, Sherin', 'Nikolaou, Elissavet', 'German, Esther L.', 'Hyder-Wright, Angie', 'Hill, Helen', 'Hales, Caz', 'de Steenhuijsen Piters, Wouter A.A', 'Bogaert, Debby', 'Adler, Hugh', 'Zaidi, Seher', 'Connor, Victoria', 'Gordon, Stephen B.', 'Rylance, Jamie', 'Nakaya, Helder I.', 'Ferreira, Daniela M.']",Nat Immunol,,,True
6df4fbfde9e9a138d60059df8d607f96db987c8c,PMC,Inflammation induced by influenza virus impairs human innate immune control of pneumococcus,http://dx.doi.org/10.1038/s41590-018-0231-y,PMC6241853,30374129,NO-CC CODE,"Colonization of the upper respiratory tract by pneumococcus is important both as a determinant of disease and for transmission into the population. The immunological mechanisms that contain pneumococcus during colonization are well studied in mice but remain unclear in humans. Loss of this control of pneumococcus following infection with influenza virus is associated with secondary bacterial pneumonia. We used a human challenge model with type 6B pneumococcus to show that acquisition of pneumococcus induced early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function was associated with the clearance of pneumococcus. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate immune function and altered genome-wide nasal gene responses to the carriage of pneumococcus. Levels of the cytokine CXCL10, promoted by viral infection, at the time pneumococcus was encountered were positively associated with bacterial load.",2018 Dec 29,"['Jochems, Simon P.', 'Marcon, Fernando', 'Carniel, Beatriz F.', 'Holloway, Mark', 'Mitsi, Elena', 'Smith, Emma', 'Gritzfeld, Jenna F.', 'Solórzano, Carla', 'Reiné, Jesús', 'Pojar, Sherin', 'Nikolaou, Elissavet', 'German, Esther L.', 'Hyder-Wright, Angie', 'Hill, Helen', 'Hales, Caz', 'de Steenhuijsen Piters, Wouter A.A', 'Bogaert, Debby', 'Adler, Hugh', 'Zaidi, Seher', 'Connor, Victoria', 'Gordon, Stephen B.', 'Rylance, Jamie', 'Nakaya, Helder I.', 'Ferreira, Daniela M.']",Nat Immunol,,,False
45b68fb7e99fffb722b9ac61ba8b0cbe00370e16,PMC,"Prevalence of Avian Influenza A(H5) and A(H9) Viruses in Live Bird Markets, Bangladesh",http://dx.doi.org/10.3201/eid2412.180879,PMC6256373,30457545,NO-CC CODE,"We conducted a cross-sectional study in live bird markets (LBMs) in Dhaka and Chittagong, Bangladesh, to estimate the prevalence of avian influenza A(H5) and A(H9) viruses in different types of poultry and environmental areas by using Bayesian hierarchical logistic regression models. We detected these viruses in nearly all LBMs. Prevalence of A(H5) virus was higher in waterfowl than in chickens, whereas prevalence of A(H9) virus was higher in chickens than in waterfowl and, among chicken types, in industrial broilers than in cross-breeds and indigenous breeds. LBMs with >1 wholesaler were more frequently contaminated by A(H5) virus than retail-only LBMs. Prevalence of A(H9) virus in poultry and level of environmental contamination were also higher in LBMs with >1 wholesaler. We found a high level of circulation of both avian influenza viruses in surveyed LBMs. Prevalence was influenced by type of poultry, environmental site, and trading.",2018 Dec,"['Kim, Younjung', 'Biswas, Paritosh K.', 'Giasuddin, Mohammad', 'Hasan, Mahmudul', 'Mahmud, Rashed', 'Chang, Yu-Mei', 'Essen, Steve', 'Samad, Mohammed A.', 'Lewis, Nicola S.', 'Brown, Ian H.', 'Moyen, Natalie', 'Hoque, Md. Ahasanul', 'Debnath, Nitish C.', 'Pfeiffer, Dirk U.', 'Fournié, Guillaume']",Emerg Infect Dis,,,True
7d242efb7ad314969a91aad0d02714ed5c871591,PMC,"Prevalence of Avian Influenza A(H5) and A(H9) Viruses in Live Bird Markets, Bangladesh",http://dx.doi.org/10.3201/eid2412.180879,PMC6256373,30457545,NO-CC CODE,"We conducted a cross-sectional study in live bird markets (LBMs) in Dhaka and Chittagong, Bangladesh, to estimate the prevalence of avian influenza A(H5) and A(H9) viruses in different types of poultry and environmental areas by using Bayesian hierarchical logistic regression models. We detected these viruses in nearly all LBMs. Prevalence of A(H5) virus was higher in waterfowl than in chickens, whereas prevalence of A(H9) virus was higher in chickens than in waterfowl and, among chicken types, in industrial broilers than in cross-breeds and indigenous breeds. LBMs with >1 wholesaler were more frequently contaminated by A(H5) virus than retail-only LBMs. Prevalence of A(H9) virus in poultry and level of environmental contamination were also higher in LBMs with >1 wholesaler. We found a high level of circulation of both avian influenza viruses in surveyed LBMs. Prevalence was influenced by type of poultry, environmental site, and trading.",2018 Dec,"['Kim, Younjung', 'Biswas, Paritosh K.', 'Giasuddin, Mohammad', 'Hasan, Mahmudul', 'Mahmud, Rashed', 'Chang, Yu-Mei', 'Essen, Steve', 'Samad, Mohammed A.', 'Lewis, Nicola S.', 'Brown, Ian H.', 'Moyen, Natalie', 'Hoque, Md. Ahasanul', 'Debnath, Nitish C.', 'Pfeiffer, Dirk U.', 'Fournié, Guillaume']",Emerg Infect Dis,,,False
0861c56539f701b2d23d2860dab6cf4ede3c823a,PMC,"Prevalence of Avian Influenza A(H5) and A(H9) Viruses in Live Bird Markets, Bangladesh",http://dx.doi.org/10.3201/eid2412.180879,PMC6256373,30457545,NO-CC CODE,"We conducted a cross-sectional study in live bird markets (LBMs) in Dhaka and Chittagong, Bangladesh, to estimate the prevalence of avian influenza A(H5) and A(H9) viruses in different types of poultry and environmental areas by using Bayesian hierarchical logistic regression models. We detected these viruses in nearly all LBMs. Prevalence of A(H5) virus was higher in waterfowl than in chickens, whereas prevalence of A(H9) virus was higher in chickens than in waterfowl and, among chicken types, in industrial broilers than in cross-breeds and indigenous breeds. LBMs with >1 wholesaler were more frequently contaminated by A(H5) virus than retail-only LBMs. Prevalence of A(H9) virus in poultry and level of environmental contamination were also higher in LBMs with >1 wholesaler. We found a high level of circulation of both avian influenza viruses in surveyed LBMs. Prevalence was influenced by type of poultry, environmental site, and trading.",2018 Dec,"['Kim, Younjung', 'Biswas, Paritosh K.', 'Giasuddin, Mohammad', 'Hasan, Mahmudul', 'Mahmud, Rashed', 'Chang, Yu-Mei', 'Essen, Steve', 'Samad, Mohammed A.', 'Lewis, Nicola S.', 'Brown, Ian H.', 'Moyen, Natalie', 'Hoque, Md. Ahasanul', 'Debnath, Nitish C.', 'Pfeiffer, Dirk U.', 'Fournié, Guillaume']",Emerg Infect Dis,,,False
18d1ff1667652b4e383a0a1ea258db97ac74735c,PMC,The interactome: Predicting the protein-protein interactions in cells,http://dx.doi.org/10.2478/s11658-008-0024-7,PMC6275871,18839074,NO-CC CODE,"The term Interactome describes the set of all molecular interactions in cells, especially in the context of protein-protein interactions. These interactions are crucial for most cellular processes, so the full representation of the interaction repertoire is needed to understand the cell molecular machinery at the system biology level. In this short review, we compare various methods for predicting protein-protein interactions using sequence and structure information. The ultimate goal of those approaches is to present the complete methodology for the automatic selection of interaction partners using their amino acid sequences and/or three dimensional structures, if known. Apart from a description of each method, details of the software or web interface needed for high throughput prediction on the whole genome scale are also provided. The proposed validation of the theoretical methods using experimental data would be a better assessment of their accuracy.",2008 Oct 6,"['Plewczyński, Dariusz', 'Ginalski, Krzysztof']",Cell Mol Biol Lett,,,True
4be1c96386ee9f1750f185e5f790425215cc0075,PMC,Origins and Evolution of the Global RNA Virome,http://dx.doi.org/10.1128/mBio.02329-18,PMC6282212,30482837,NO-CC CODE,"Viruses with RNA genomes dominate the eukaryotic virome, reaching enormous diversity in animals and plants. The recent advances of metaviromics prompted us to perform a detailed phylogenomic reconstruction of the evolution of the dramatically expanded global RNA virome. The only universal gene among RNA viruses is the gene encoding the RNA-dependent RNA polymerase (RdRp). We developed an iterative computational procedure that alternates the RdRp phylogenetic tree construction with refinement of the underlying multiple-sequence alignments. The resulting tree encompasses 4,617 RNA virus RdRps and consists of 5 major branches; 2 of the branches include positive-sense RNA viruses, 1 is a mix of positive-sense (+) RNA and double-stranded RNA (dsRNA) viruses, and 2 consist of dsRNA and negative-sense (−) RNA viruses, respectively. This tree topology implies that dsRNA viruses evolved from +RNA viruses on at least two independent occasions, whereas −RNA viruses evolved from dsRNA viruses. Reconstruction of RNA virus evolution using the RdRp tree as the scaffold suggests that the last common ancestors of the major branches of +RNA viruses encoded only the RdRp and a single jelly-roll capsid protein. Subsequent evolution involved independent capture of additional genes, in particular, those encoding distinct RNA helicases, enabling replication of larger RNA genomes and facilitating virus genome expression and virus-host interactions. Phylogenomic analysis reveals extensive gene module exchange among diverse viruses and horizontal virus transfer between distantly related hosts. Although the network of evolutionary relationships within the RNA virome is bound to further expand, the present results call for a thorough reevaluation of the RNA virus taxonomy.",2018 Nov 27,"['Wolf, Yuri I.', 'Kazlauskas, Darius', 'Iranzo, Jaime', 'Lucía-Sanz, Adriana', 'Kuhn, Jens H.', 'Krupovic, Mart', 'Dolja, Valerian V.', 'Koonin, Eugene V.']",mBio,,,True
afc7ba033c2b5d26bf0ae5ff3f45f950cedb7243,PMC,Origins and Evolution of the Global RNA Virome,http://dx.doi.org/10.1128/mBio.02329-18,PMC6282212,30482837,NO-CC CODE,"Viruses with RNA genomes dominate the eukaryotic virome, reaching enormous diversity in animals and plants. The recent advances of metaviromics prompted us to perform a detailed phylogenomic reconstruction of the evolution of the dramatically expanded global RNA virome. The only universal gene among RNA viruses is the gene encoding the RNA-dependent RNA polymerase (RdRp). We developed an iterative computational procedure that alternates the RdRp phylogenetic tree construction with refinement of the underlying multiple-sequence alignments. The resulting tree encompasses 4,617 RNA virus RdRps and consists of 5 major branches; 2 of the branches include positive-sense RNA viruses, 1 is a mix of positive-sense (+) RNA and double-stranded RNA (dsRNA) viruses, and 2 consist of dsRNA and negative-sense (−) RNA viruses, respectively. This tree topology implies that dsRNA viruses evolved from +RNA viruses on at least two independent occasions, whereas −RNA viruses evolved from dsRNA viruses. Reconstruction of RNA virus evolution using the RdRp tree as the scaffold suggests that the last common ancestors of the major branches of +RNA viruses encoded only the RdRp and a single jelly-roll capsid protein. Subsequent evolution involved independent capture of additional genes, in particular, those encoding distinct RNA helicases, enabling replication of larger RNA genomes and facilitating virus genome expression and virus-host interactions. Phylogenomic analysis reveals extensive gene module exchange among diverse viruses and horizontal virus transfer between distantly related hosts. Although the network of evolutionary relationships within the RNA virome is bound to further expand, the present results call for a thorough reevaluation of the RNA virus taxonomy.",2018 Nov 27,"['Wolf, Yuri I.', 'Kazlauskas, Darius', 'Iranzo, Jaime', 'Lucía-Sanz, Adriana', 'Kuhn, Jens H.', 'Krupovic, Mart', 'Dolja, Valerian V.', 'Koonin, Eugene V.']",mBio,,,False
b18fc8758e513f6ce7c504f0adf2cc539477b610,PMC,Origins and Evolution of the Global RNA Virome,http://dx.doi.org/10.1128/mBio.02329-18,PMC6282212,30482837,NO-CC CODE,"Viruses with RNA genomes dominate the eukaryotic virome, reaching enormous diversity in animals and plants. The recent advances of metaviromics prompted us to perform a detailed phylogenomic reconstruction of the evolution of the dramatically expanded global RNA virome. The only universal gene among RNA viruses is the gene encoding the RNA-dependent RNA polymerase (RdRp). We developed an iterative computational procedure that alternates the RdRp phylogenetic tree construction with refinement of the underlying multiple-sequence alignments. The resulting tree encompasses 4,617 RNA virus RdRps and consists of 5 major branches; 2 of the branches include positive-sense RNA viruses, 1 is a mix of positive-sense (+) RNA and double-stranded RNA (dsRNA) viruses, and 2 consist of dsRNA and negative-sense (−) RNA viruses, respectively. This tree topology implies that dsRNA viruses evolved from +RNA viruses on at least two independent occasions, whereas −RNA viruses evolved from dsRNA viruses. Reconstruction of RNA virus evolution using the RdRp tree as the scaffold suggests that the last common ancestors of the major branches of +RNA viruses encoded only the RdRp and a single jelly-roll capsid protein. Subsequent evolution involved independent capture of additional genes, in particular, those encoding distinct RNA helicases, enabling replication of larger RNA genomes and facilitating virus genome expression and virus-host interactions. Phylogenomic analysis reveals extensive gene module exchange among diverse viruses and horizontal virus transfer between distantly related hosts. Although the network of evolutionary relationships within the RNA virome is bound to further expand, the present results call for a thorough reevaluation of the RNA virus taxonomy.",2018 Nov 27,"['Wolf, Yuri I.', 'Kazlauskas, Darius', 'Iranzo, Jaime', 'Lucía-Sanz, Adriana', 'Kuhn, Jens H.', 'Krupovic, Mart', 'Dolja, Valerian V.', 'Koonin, Eugene V.']",mBio,,,False
d49bfb1a593fb511f71765af7bcc14cfe7a25b6b,PMC,Origins and Evolution of the Global RNA Virome,http://dx.doi.org/10.1128/mBio.02329-18,PMC6282212,30482837,NO-CC CODE,"Viruses with RNA genomes dominate the eukaryotic virome, reaching enormous diversity in animals and plants. The recent advances of metaviromics prompted us to perform a detailed phylogenomic reconstruction of the evolution of the dramatically expanded global RNA virome. The only universal gene among RNA viruses is the gene encoding the RNA-dependent RNA polymerase (RdRp). We developed an iterative computational procedure that alternates the RdRp phylogenetic tree construction with refinement of the underlying multiple-sequence alignments. The resulting tree encompasses 4,617 RNA virus RdRps and consists of 5 major branches; 2 of the branches include positive-sense RNA viruses, 1 is a mix of positive-sense (+) RNA and double-stranded RNA (dsRNA) viruses, and 2 consist of dsRNA and negative-sense (−) RNA viruses, respectively. This tree topology implies that dsRNA viruses evolved from +RNA viruses on at least two independent occasions, whereas −RNA viruses evolved from dsRNA viruses. Reconstruction of RNA virus evolution using the RdRp tree as the scaffold suggests that the last common ancestors of the major branches of +RNA viruses encoded only the RdRp and a single jelly-roll capsid protein. Subsequent evolution involved independent capture of additional genes, in particular, those encoding distinct RNA helicases, enabling replication of larger RNA genomes and facilitating virus genome expression and virus-host interactions. Phylogenomic analysis reveals extensive gene module exchange among diverse viruses and horizontal virus transfer between distantly related hosts. Although the network of evolutionary relationships within the RNA virome is bound to further expand, the present results call for a thorough reevaluation of the RNA virus taxonomy.",2018 Nov 27,"['Wolf, Yuri I.', 'Kazlauskas, Darius', 'Iranzo, Jaime', 'Lucía-Sanz, Adriana', 'Kuhn, Jens H.', 'Krupovic, Mart', 'Dolja, Valerian V.', 'Koonin, Eugene V.']",mBio,,,False
850dc8add6efb76a6dc341cb7a5a236c1dd3da7c,PMC,Expanded skin virome in DOCK8-deficient patients,http://dx.doi.org/10.1038/s41591-018-0211-7,PMC6286253,30397357,NO-CC CODE,"Human microbiome studies have revealed the intricate interplay of host immunity and bacterial communities to achieve homeostatic balance. Healthy skin microbial communities are dominated by bacteria with low viral representation(1–3), mainly bacteriophage. Specific eukaryotic viruses have been implicated in both common and rare skin diseases, but cataloging skin viral communities has been limited. Alterations in host immunity provide an opportunity to expand our understanding of microbial-host interactions. Primary immunedeficient patients manifest with various viral bacterial, fungal and parasitic infections, including skin infections(4). Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare primary human immunodeficiency characterized by recurrent cutaneous and systemic infections, as well as atopy and cancer susceptibility(5). DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes, regulates actin cytoskeleton, which is critical for migration through collagen-dense tissues, such as skin(6). Analyzing deep metagenomic sequencing data from DOCK8-deficient skin samples demonstrated a notable increase in eukaryotic viral representation and diversity as compared to healthy volunteers. De novo assembly approaches identified hundreds of novel human papillomavirus genomes, illuminating microbial dark matter. Expansion of the skin virome in DOCK8-deficient patients underscores the importance of immune surveillance in controlling eukaryotic viral colonization and infection.",2018 Dec 5,"['Tirosh, Osnat', 'Conlan, Sean', 'Deming, Clay', 'Lee-Lin, Shih-Queen', 'Huang, Xin', None, 'Su, Helen C.', 'Freeman, Alexandra F.', 'Segre, Julia A.', 'Kong, Heidi H.']",Nat Med,,,True
fe33ff01234dd6a16c30bf14916d1b32c4a940fd,PMC,The Human Sodium Iodide Symporter as a Reporter Gene for Studying Middle East Respiratory Syndrome Coronavirus Pathogenesis,http://dx.doi.org/10.1128/mSphere.00540-18,PMC6291621,30541777,NO-CC CODE,"Single photon emission computed tomography (SPECT) is frequently used in oncology and cardiology to evaluate disease progression and/or treatment efficacy. Such technology allows for real-time evaluation of disease progression and when applied to studying infectious diseases may provide insight into pathogenesis. Insertion of a SPECT-compatible reporter gene into a virus may provide insight into mechanisms of pathogenesis and viral tropism. The human sodium iodide symporter (hNIS), a SPECT and positron emission tomography reporter gene, was inserted into Middle East respiratory syndrome coronavirus (MERS-CoV), a recently emerged virus that can cause severe respiratory disease and death in afflicted humans to obtain a quantifiable and sensitive marker for viral replication to further MERS-CoV animal model development. The recombinant virus was evaluated for fitness, stability, and reporter gene functionality. The recombinant and parental viruses demonstrated equal fitness in terms of peak titer and replication kinetics, were stable for up to six in vitro passages, and were functional. Further in vivo evaluation indicated variable stability, but resolution limits hampered in vivo functional evaluation. These data support the further development of hNIS for monitoring infection in animal models of viral disease. IMPORTANCE Advanced medical imaging such as single photon emission computed tomography with computed tomography (SPECT/CT) enhances fields such as oncology and cardiology. Application of SPECT/CT, magnetic resonance imaging, and positron emission tomography to infectious disease may enhance pathogenesis studies and provide alternate biomarkers of disease progression. The experiments described in this article focus on insertion of a SPECT/CT-compatible reporter gene into MERS-CoV to demonstrate that a functional SPECT/CT reporter gene can be inserted into a virus.",2018 Dec 12,"['Chefer, Svetlana', 'Seidel, Jurgen', 'Cockrell, Adam S.', 'Yount, Boyd', 'Solomon, Jeffrey', 'Hagen, Katie R.', 'Liu, David X.', 'Huzella, Louis M.', 'Kumar, Mia R.', 'Postnikova, Elena', 'Bohannon, J. Kyle', 'Lackemeyer, Matthew G.', 'Cooper, Kurt', 'Endlich-Frazier, Ariel', 'Sharma, Heema', 'Thomasson, David', 'Bartos, Christopher', 'Sayre, Philip J.', 'Sims, Amy', 'Dyall, Julie', 'Holbrook, Michael R.', 'Jahrling, Peter B.', 'Baric, Ralph S.', 'Johnson, Reed F.']",mSphere,,,True
fa10fc18bd2064be259b140244eea81e9adb29d1,PMC,In Memoriam: Katrin Susanne Kohl (1964–2018),http://dx.doi.org/10.3201/eid2501.180961,PMC6302588,,NO-CC CODE,,2019 Jan,"['Marano, Nina', 'Waterman, Stephen H.']",Emerg Infect Dis,,,False
584aa286fb6e7f2404ff67c5cfa025b33e110214,PMC,"Epidemiology of Imported Infectious Diseases, China, 2005–2016",http://dx.doi.org/10.3201/eid2501.180178,PMC6302593,30560778,NO-CC CODE,"Imported infectious diseases are becoming a serious public health threat in China. However, limited information concerning the epidemiologic characteristics of imported infectious diseases is available. In this study, we collected data related to imported infectious diseases in mainland China from the National Information Reporting System of Infectious Diseases and analyzed demographic, temporal, and spatial distributions. The number of types of imported infectious diseases reported increased from 2 in 2005 to 11 in 2016. A total of 31,740 cases of infectious disease were imported to mainland China during 2005–2016; most of them were found in Yunnan Province. The cases were imported mainly from Africa and Asia. As a key and effective measure, pretravel education should be strengthened for all migrant workers and tourists in China, and border screening, cross-border international cooperation, and early warning should be further improved.",2019 Jan,"['Wang, Yali', 'Wang, Xuan', 'Liu, Xiaobo', 'Ren, Ruiqi', 'Zhou, Lei', 'Li, Chao', 'Tu, Wenxiao', 'Ni, Daxin', 'Li, Qun', 'Feng, Zijian', 'Zhang, Yanping']",Emerg Infect Dis,,,True
4c7f6c52fe043745887db5406196b1d5099c9614,PMC,Multiple Introductions of Domestic Cat Feline Leukemia Virus in Endangered Florida Panthers,http://dx.doi.org/10.3201/eid2501.181347,PMC6302599,30561312,NO-CC CODE,"The endangered Florida panther (Puma concolor coryi) had an outbreak of infection with feline leukemia virus (FeLV) in the early 2000s that resulted in the deaths of 3 animals. A vaccination campaign was instituted during 2003–2007 and no additional cases were recorded until 2010. During 2010–2016, six additional FeLV cases were documented. We characterized FeLV genomes isolated from Florida panthers from both outbreaks and compared them with full-length genomes of FeLVs isolated from contemporary Florida domestic cats. Phylogenetic analyses identified at least 2 circulating FeLV strains in panthers, which represent separate introductions from domestic cats. The original FeLV virus outbreak strain is either still circulating or another domestic cat transmission event has occurred with a closely related variant. We also report a case of a cross-species transmission event of an oncogenic FeLV recombinant (FeLV-B). Evidence of multiple FeLV strains and detection of FeLV-B indicate Florida panthers are at high risk for FeLV infection.",2019 Jan,"['Chiu, Elliott S.', 'Kraberger, Simona', 'Cunningham, Mark', 'Cusack, Lara', 'Roelke, Melody', 'VandeWoude, Sue']",Emerg Infect Dis,,,True
1b459b40702f394c31ceac6910e262b63c939d56,PMC,Multiple Introductions of Domestic Cat Feline Leukemia Virus in Endangered Florida Panthers,http://dx.doi.org/10.3201/eid2501.181347,PMC6302599,30561312,NO-CC CODE,"The endangered Florida panther (Puma concolor coryi) had an outbreak of infection with feline leukemia virus (FeLV) in the early 2000s that resulted in the deaths of 3 animals. A vaccination campaign was instituted during 2003–2007 and no additional cases were recorded until 2010. During 2010–2016, six additional FeLV cases were documented. We characterized FeLV genomes isolated from Florida panthers from both outbreaks and compared them with full-length genomes of FeLVs isolated from contemporary Florida domestic cats. Phylogenetic analyses identified at least 2 circulating FeLV strains in panthers, which represent separate introductions from domestic cats. The original FeLV virus outbreak strain is either still circulating or another domestic cat transmission event has occurred with a closely related variant. We also report a case of a cross-species transmission event of an oncogenic FeLV recombinant (FeLV-B). Evidence of multiple FeLV strains and detection of FeLV-B indicate Florida panthers are at high risk for FeLV infection.",2019 Jan,"['Chiu, Elliott S.', 'Kraberger, Simona', 'Cunningham, Mark', 'Cusack, Lara', 'Roelke, Melody', 'VandeWoude, Sue']",Emerg Infect Dis,,,False
4f2102dfde801cb0cab691992bbc61cbd98b1ca5,PMC,International Biological Reference Preparations for Epidemic Infectious Diseases,http://dx.doi.org/10.3201/eid2502.180798,PMC6346470,30666925,NO-CC CODE,"Recent years have seen unprecedented investment in research and development for countermeasures for high-threat pathogens, including specific and ambitious objectives for development of diagnostics, therapeutics, and vaccines. The inadequate availability of biological reference materials for these pathogens poses a genuine obstacle in pursuit of these objectives, and the lack of a comprehensive and equitable framework for developing reference materials is a weakness. We outline the need for internationally standardized biological materials for high-threat pathogens as a core element of global health security. We also outline the key components of a framework for addressing this deficiency.",2019 Feb,"['Rampling, Tommy', 'Page, Mark', 'Horby, Peter']",Emerg Infect Dis,,,True
9f5b88ccb461ad00982bfad6778331faf6840982,PMC,"Bat Influenza A(HL18NL11) Virus in Fruit Bats, Brazil",http://dx.doi.org/10.3201/eid2502.181246,PMC6346480,30666923,NO-CC CODE,"Screening of 533 bats for influenza A viruses showed subtype HL18NL11 in intestines of 2 great fruit-eating bats (Artibeus lituratus). High concentrations suggested fecal shedding. Genomic characterizations revealed conservation of viral genes across different host species, countries, and sampling years, suggesting a conserved cellular receptor and wide-ranging occurrence of bat influenza A viruses.",2019 Feb,"['Campos, Angélica Cristine Almeida', 'Góes, Luiz Gustavo Bentim', 'Moreira-Soto, Andres', 'de Carvalho, Cristiano', 'Ambar, Guilherme', 'Sander, Anna-Lena', 'Fischer, Carlo', 'Ruckert da Rosa, Adriana', 'Cardoso de Oliveira, Debora', 'Kataoka, Ana Paula G.', 'Pedro, Wagner André', 'Martorelli, Luzia Fátima A.', 'Queiroz, Luzia Helena', 'Cruz-Neto, Ariovaldo P.', 'Durigon, Edison Luiz', 'Drexler, Jan Felix']",Emerg Infect Dis,,,True
e03d9deb64a67ebb6c09feef45cf6030cc7c3b31,PMC,"Bat Influenza A(HL18NL11) Virus in Fruit Bats, Brazil",http://dx.doi.org/10.3201/eid2502.181246,PMC6346480,30666923,NO-CC CODE,"Screening of 533 bats for influenza A viruses showed subtype HL18NL11 in intestines of 2 great fruit-eating bats (Artibeus lituratus). High concentrations suggested fecal shedding. Genomic characterizations revealed conservation of viral genes across different host species, countries, and sampling years, suggesting a conserved cellular receptor and wide-ranging occurrence of bat influenza A viruses.",2019 Feb,"['Campos, Angélica Cristine Almeida', 'Góes, Luiz Gustavo Bentim', 'Moreira-Soto, Andres', 'de Carvalho, Cristiano', 'Ambar, Guilherme', 'Sander, Anna-Lena', 'Fischer, Carlo', 'Ruckert da Rosa, Adriana', 'Cardoso de Oliveira, Debora', 'Kataoka, Ana Paula G.', 'Pedro, Wagner André', 'Martorelli, Luzia Fátima A.', 'Queiroz, Luzia Helena', 'Cruz-Neto, Ariovaldo P.', 'Durigon, Edison Luiz', 'Drexler, Jan Felix']",Emerg Infect Dis,,,False
bc3575cce4fb95a77596f85eec9ad9e75137e06e,PMC,Inorganic Complexes and Metal-Based Nanomaterials for Infectious Disease Diagnostics,http://dx.doi.org/10.1021/acs.chemrev.8b00136,PMC6348445,30511833,NO-CC CODE,"[Image: see text] Infectious diseases claim millions of lives each year. Robust and accurate diagnostics are essential tools for identifying those who are at risk and in need of treatment in low-resource settings. Inorganic complexes and metal-based nanomaterials continue to drive the development of diagnostic platforms and strategies that enable infectious disease detection in low-resource settings. In this review, we highlight works from the past 20 years in which inorganic chemistry and nanotechnology were implemented in each of the core components that make up a diagnostic test. First, we present how inorganic biomarkers and their properties are leveraged for infectious disease detection. In the following section, we detail metal-based technologies that have been employed for sample preparation and biomarker isolation from sample matrices. We then describe how inorganic- and nanomaterial-based probes have been utilized in point-of-care diagnostics for signal generation. The following section discusses instrumentation for signal readout in resource-limited settings. Next, we highlight the detection of nucleic acids at the point of care as an emerging application of inorganic chemistry. Lastly, we consider the challenges that remain for translation of the aforementioned diagnostic platforms to low-resource settings.",2019 Jan 23,"['Markwalter, Christine\nF.', 'Kantor, Andrew G.', 'Moore, Carson P.', 'Richardson, Kelly A.', 'Wright, David W.']",Chem Rev,,,True
cf692fd14d468eaca2c460132802463f0747411e,PMC,Survey on Implementation of One Health Approach for MERS-CoV Preparedness and Control in Gulf Cooperation Council and Middle East Countries,http://dx.doi.org/10.3201/eid2503.171702,PMC6390738,30789338,NO-CC CODE,"In 2015, a One Health Working Group was established in Qatar to conduct a survey in the Gulf Cooperation Council countries, Egypt, and Jordan to monitor preparedness of public health and veterinary health authorities in response to the Middle East respiratory syndrome coronavirus epidemic. All but 1 country indicated they established joint One Health policy teams for investigation and response. However, the response to the questionnaires was largely limited to veterinary authorities. Critical barriers and limitations were identified. National and regional leaders, policy makers, and stakeholders should be prompted to advocate and enhance adoption of the One Health framework to mitigate the risk for Middle East respiratory syndrome and other emerging zoonotic diseases.",2019 Mar,"['Farag, Elmoubasher Abu Baker', 'Nour, Mohamed', 'El Idrissi, Ahmed', 'Berrada, Jaouad', 'Moustafa, Aya', 'Mehmood, Minahil', 'Mahmoud, Mahmoud H.', 'El-Sayed, Ahmed M.', 'Alhajri, Farhoud', 'Al-Hajri, Mohammed', 'Hassan, Osama Ahmed', 'Al-Romaihi, Hamad', 'Al-Thani, Mohamed', 'Al-Marri, Salih A.', 'Koopmans, Marion P.G.', 'Ismail, Mohamed Haroun']",Emerg Infect Dis,,,True
84e2013635e4484e5837fb190fad90a871e0f714,PMC,"Case Investigations of Infectious Diseases Occurring in Workplaces, United States, 2006–2015",http://dx.doi.org/10.3201/eid2503.180708,PMC6390751,30789129,NO-CC CODE,"Workers in specific settings and activities are at increased risk for certain infectious diseases. When an infectious disease case occurs in a worker, investigators need to understand the mechanisms of disease propagation in the workplace. Few publications have explored these factors in the United States; a literature search yielded 66 investigations of infectious disease occurring in US workplaces during 2006–2015. Reported cases appear to be concentrated in specific industries and occupations, especially the healthcare industry, laboratory workers, animal workers, and public service workers. A hierarchy-of-controls approach can help determine how to implement effective preventive measures in workplaces. Consideration of occupational risk factors and control of occupational exposures will help prevent disease transmission in the workplace and protect workers’ health.",2019 Mar,"['Su, Chia-ping', 'de Perio, Marie A.', 'Cummings, Kristin J.', 'McCague, Anna-Binney', 'Luckhaupt, Sara E.', 'Sweeney, Marie Haring']",Emerg Infect Dis,,,True
7f5099683746562c52ba0577d95b02864b1d2661,PMC,"Case Investigations of Infectious Diseases Occurring in Workplaces, United States, 2006–2015",http://dx.doi.org/10.3201/eid2503.180708,PMC6390751,30789129,NO-CC CODE,"Workers in specific settings and activities are at increased risk for certain infectious diseases. When an infectious disease case occurs in a worker, investigators need to understand the mechanisms of disease propagation in the workplace. Few publications have explored these factors in the United States; a literature search yielded 66 investigations of infectious disease occurring in US workplaces during 2006–2015. Reported cases appear to be concentrated in specific industries and occupations, especially the healthcare industry, laboratory workers, animal workers, and public service workers. A hierarchy-of-controls approach can help determine how to implement effective preventive measures in workplaces. Consideration of occupational risk factors and control of occupational exposures will help prevent disease transmission in the workplace and protect workers’ health.",2019 Mar,"['Su, Chia-ping', 'de Perio, Marie A.', 'Cummings, Kristin J.', 'McCague, Anna-Binney', 'Luckhaupt, Sara E.', 'Sweeney, Marie Haring']",Emerg Infect Dis,,,True
e32e94fd63e050881d16e0c938820df16fdeadb2,PMC,"Middle East Respiratory Syndrome Coronavirus Infection Dynamics and Antibody Responses among Clinically Diverse Patients, Saudi Arabia",http://dx.doi.org/10.3201/eid2504.181595,PMC6433025,30882305,NO-CC CODE,"Middle East respiratory syndrome coronavirus (MERS-CoV) shedding and antibody responses are not fully understood, particularly in relation to underlying medical conditions, clinical manifestations, and mortality. We enrolled MERS-CoV–positive patients at a hospital in Saudi Arabia and periodically collected specimens from multiple sites for real-time reverse transcription PCR and serologic testing. We conducted interviews and chart abstractions to collect clinical, epidemiologic, and laboratory information. We found that diabetes mellitus among survivors was associated with prolonged MERS-CoV RNA detection in the respiratory tract. Among case-patients who died, development of robust neutralizing serum antibody responses during the second and third week of illness was not sufficient for patient recovery or virus clearance. Fever and cough among mildly ill patients typically aligned with RNA detection in the upper respiratory tract; RNA levels peaked during the first week of illness. These findings should be considered in the development of infection control policies, vaccines, and antibody therapeutics.",2019 Apr,"['Al-Abdely, Hail M.', 'Midgley, Claire M.', 'Alkhamis, Abdulrahim M.', 'Abedi, Glen R.', 'Lu, Xiaoyan', 'Binder, Alison M.', 'Alanazi, Khalid H.', 'Tamin, Azaibi', 'Banjar, Weam M.', 'Lester, Sandra', 'Abdalla, Osman', 'Dahl, Rebecca M.', 'Mohammed, Mutaz', 'Trivedi, Suvang', 'Algarni, Homoud S.', 'Sakthivel, Senthilkumar K.', 'Algwizani, Abdullah', 'Bafaqeeh, Fahad', 'Alzahrani, Abdullah', 'Alsharef, Ali Abraheem', 'Alhakeem, Raafat F.', 'Jokhdar, Hani A. Aziz', 'Ghazal, Sameeh S.', 'Thornburg, Natalie J.', 'Erdman, Dean D.', 'Assiri, Abdullah M.', 'Watson, John T.', 'Gerber, Susan I.']",Emerg Infect Dis,,,True
356e180c8bed920420d2b6c5ad48ba9a4568da31,PMC,"Middle East Respiratory Syndrome Coronavirus Infection Dynamics and Antibody Responses among Clinically Diverse Patients, Saudi Arabia",http://dx.doi.org/10.3201/eid2504.181595,PMC6433025,30882305,NO-CC CODE,"Middle East respiratory syndrome coronavirus (MERS-CoV) shedding and antibody responses are not fully understood, particularly in relation to underlying medical conditions, clinical manifestations, and mortality. We enrolled MERS-CoV–positive patients at a hospital in Saudi Arabia and periodically collected specimens from multiple sites for real-time reverse transcription PCR and serologic testing. We conducted interviews and chart abstractions to collect clinical, epidemiologic, and laboratory information. We found that diabetes mellitus among survivors was associated with prolonged MERS-CoV RNA detection in the respiratory tract. Among case-patients who died, development of robust neutralizing serum antibody responses during the second and third week of illness was not sufficient for patient recovery or virus clearance. Fever and cough among mildly ill patients typically aligned with RNA detection in the upper respiratory tract; RNA levels peaked during the first week of illness. These findings should be considered in the development of infection control policies, vaccines, and antibody therapeutics.",2019 Apr,"['Al-Abdely, Hail M.', 'Midgley, Claire M.', 'Alkhamis, Abdulrahim M.', 'Abedi, Glen R.', 'Lu, Xiaoyan', 'Binder, Alison M.', 'Alanazi, Khalid H.', 'Tamin, Azaibi', 'Banjar, Weam M.', 'Lester, Sandra', 'Abdalla, Osman', 'Dahl, Rebecca M.', 'Mohammed, Mutaz', 'Trivedi, Suvang', 'Algarni, Homoud S.', 'Sakthivel, Senthilkumar K.', 'Algwizani, Abdullah', 'Bafaqeeh, Fahad', 'Alzahrani, Abdullah', 'Alsharef, Ali Abraheem', 'Alhakeem, Raafat F.', 'Jokhdar, Hani A. Aziz', 'Ghazal, Sameeh S.', 'Thornburg, Natalie J.', 'Erdman, Dean D.', 'Assiri, Abdullah M.', 'Watson, John T.', 'Gerber, Susan I.']",Emerg Infect Dis,,,True
35e9db94099acc5ce344cdf3a2189d69616a12e9,PMC,Dynamic and Cell-Infiltratable Hydrogels as Injectable Carrier of Therapeutic Cells and Drugs for Treating Challenging Bone Defects,http://dx.doi.org/10.1021/acscentsci.8b00764,PMC6439455,30937371,NO-CC CODE,"[Image: see text] Biopolymeric hydrogels have been widely used as carriers of therapeutic cells and drugs for biomedical applications. However, most conventional hydrogels cannot be injected after gelation and do not support the infiltration of cells because of the static nature of their network structure. Here, we develop unique cell-infiltratable and injectable (Ci-I) gelatin hydrogels, which are physically cross-linked by weak and highly dynamic host–guest complexations and are further reinforced by limited chemical cross-linking for enhanced stability, and then demonstrate the outstanding properties of these Ci-I gelatin hydrogels. The highly dynamic network of Ci-I hydrogels allows injection of prefabricated hydrogels with encapsulated cells and drugs, thereby simplifying administration during surgery. Furthermore, the reversible nature of the weak host–guest cross-links enables infiltration and migration of external cells into Ci-I gelatin hydrogels, thereby promoting the participation of endogenous cells in the healing process. Our findings show that Ci-I hydrogels can mediate sustained delivery of small hydrophobic molecular drugs (e.g., icaritin) to boost differentiation of stem cells while avoiding the adverse effects (e.g., in treatment of bone necrosis) associated with high drug dosage. The injection of Ci-I hydrogels encapsulating mesenchymal stem cells (MSCs) and drug (icaritin) efficiently prevented the decrease in bone mineral density (BMD) and promoted in situ bone regeneration in an animal model of steroid-associated osteonecrosis (SAON) of the hip by creating the microenvironment favoring the osteogenic differentiation of MSCs, including the recruited endogenous cells. We believe that this is the first demonstration on applying injectable hydrogels as effective carriers of therapeutic cargo for treating dysfunctions in deep and enclosed anatomical sites via a minimally invasive procedure.",2019 Mar 27,"['Feng, Qian', 'Xu, Jiankun', 'Zhang, Kunyu', 'Yao, Hao', 'Zheng, Nianye', 'Zheng, Lizhen', 'Wang, Jiali', 'Wei, Kongchang', 'Xiao, Xiufeng', 'Qin, Ling', 'Bian, Liming']",ACS Cent Sci,,,True
3e184094797d77a9169bb3e572c2567ede84535d,PMC,Dynamic and Cell-Infiltratable Hydrogels as Injectable Carrier of Therapeutic Cells and Drugs for Treating Challenging Bone Defects,http://dx.doi.org/10.1021/acscentsci.8b00764,PMC6439455,30937371,NO-CC CODE,"[Image: see text] Biopolymeric hydrogels have been widely used as carriers of therapeutic cells and drugs for biomedical applications. However, most conventional hydrogels cannot be injected after gelation and do not support the infiltration of cells because of the static nature of their network structure. Here, we develop unique cell-infiltratable and injectable (Ci-I) gelatin hydrogels, which are physically cross-linked by weak and highly dynamic host–guest complexations and are further reinforced by limited chemical cross-linking for enhanced stability, and then demonstrate the outstanding properties of these Ci-I gelatin hydrogels. The highly dynamic network of Ci-I hydrogels allows injection of prefabricated hydrogels with encapsulated cells and drugs, thereby simplifying administration during surgery. Furthermore, the reversible nature of the weak host–guest cross-links enables infiltration and migration of external cells into Ci-I gelatin hydrogels, thereby promoting the participation of endogenous cells in the healing process. Our findings show that Ci-I hydrogels can mediate sustained delivery of small hydrophobic molecular drugs (e.g., icaritin) to boost differentiation of stem cells while avoiding the adverse effects (e.g., in treatment of bone necrosis) associated with high drug dosage. The injection of Ci-I hydrogels encapsulating mesenchymal stem cells (MSCs) and drug (icaritin) efficiently prevented the decrease in bone mineral density (BMD) and promoted in situ bone regeneration in an animal model of steroid-associated osteonecrosis (SAON) of the hip by creating the microenvironment favoring the osteogenic differentiation of MSCs, including the recruited endogenous cells. We believe that this is the first demonstration on applying injectable hydrogels as effective carriers of therapeutic cargo for treating dysfunctions in deep and enclosed anatomical sites via a minimally invasive procedure.",2019 Mar 27,"['Feng, Qian', 'Xu, Jiankun', 'Zhang, Kunyu', 'Yao, Hao', 'Zheng, Nianye', 'Zheng, Lizhen', 'Wang, Jiali', 'Wei, Kongchang', 'Xiao, Xiufeng', 'Qin, Ling', 'Bian, Liming']",ACS Cent Sci,,,True
a998defbe9236dc5f7880910ccb4b2c6f350879d,PMC,IFITM3 directly engages and shuttles incoming virus particles to lysosomes,http://dx.doi.org/10.1038/s41589-018-0213-2,PMC6466627,30643282,NO-CC CODE,"Interferon-induced transmembrane proteins (IFITMs) (1, 2 and 3) have emerged as important innate immune effectors that prevent diverse virus infections in vertebrates. However, the cellular mechanisms and live cell imaging of these small membrane proteins have been challenging to evaluate during viral entry of mammalian cells. Using CRISPR-Cas9-mediated IFITM-mutant cell lines, we demonstrate that human IFITM1, 2 and 3 act cooperatively and function in dose-dependent fashion in interferon-stimulated cells. Through site-specific fluorophore tagging and live cell imaging studies, we show IFITM3 is on endocytic vesicles that fuse with incoming virus particles and enhances the trafficking of this pathogenic cargo to lysosomes. IFITM3 trafficking is specific to restricted viruses, requires S-palmitoylation and is abrogated with loss-of-function mutants. The site-specific protein labeling and live cell imaging approaches described here should facilitate the functional analysis of host factors involved in pathogen restriction as well as their mechanisms of regulation.",2019 Mar 14,"['Spence, Jennifer S.', 'He, Ruina', 'Hoffmann, Hans-Heinrich', 'Das, Tandrila', 'Thinon, Emmanuelle', 'Rice, Charles M.', 'Peng, Tao', 'Chandran, Kartik', 'Hang, Howard C.']",Nat Chem Biol,,,True
b1760223f473dfc2a2249653a66292a89332b7e4,PMC,IFITM3 directly engages and shuttles incoming virus particles to lysosomes,http://dx.doi.org/10.1038/s41589-018-0213-2,PMC6466627,30643282,NO-CC CODE,"Interferon-induced transmembrane proteins (IFITMs) (1, 2 and 3) have emerged as important innate immune effectors that prevent diverse virus infections in vertebrates. However, the cellular mechanisms and live cell imaging of these small membrane proteins have been challenging to evaluate during viral entry of mammalian cells. Using CRISPR-Cas9-mediated IFITM-mutant cell lines, we demonstrate that human IFITM1, 2 and 3 act cooperatively and function in dose-dependent fashion in interferon-stimulated cells. Through site-specific fluorophore tagging and live cell imaging studies, we show IFITM3 is on endocytic vesicles that fuse with incoming virus particles and enhances the trafficking of this pathogenic cargo to lysosomes. IFITM3 trafficking is specific to restricted viruses, requires S-palmitoylation and is abrogated with loss-of-function mutants. The site-specific protein labeling and live cell imaging approaches described here should facilitate the functional analysis of host factors involved in pathogen restriction as well as their mechanisms of regulation.",2019 Mar 14,"['Spence, Jennifer S.', 'He, Ruina', 'Hoffmann, Hans-Heinrich', 'Das, Tandrila', 'Thinon, Emmanuelle', 'Rice, Charles M.', 'Peng, Tao', 'Chandran, Kartik', 'Hang, Howard C.']",Nat Chem Biol,,,True
29b884679d85a0231b62c156f3a49382de0b99fe,PMC,IFITM3 directly engages and shuttles incoming virus particles to lysosomes,http://dx.doi.org/10.1038/s41589-018-0213-2,PMC6466627,30643282,NO-CC CODE,"Interferon-induced transmembrane proteins (IFITMs) (1, 2 and 3) have emerged as important innate immune effectors that prevent diverse virus infections in vertebrates. However, the cellular mechanisms and live cell imaging of these small membrane proteins have been challenging to evaluate during viral entry of mammalian cells. Using CRISPR-Cas9-mediated IFITM-mutant cell lines, we demonstrate that human IFITM1, 2 and 3 act cooperatively and function in dose-dependent fashion in interferon-stimulated cells. Through site-specific fluorophore tagging and live cell imaging studies, we show IFITM3 is on endocytic vesicles that fuse with incoming virus particles and enhances the trafficking of this pathogenic cargo to lysosomes. IFITM3 trafficking is specific to restricted viruses, requires S-palmitoylation and is abrogated with loss-of-function mutants. The site-specific protein labeling and live cell imaging approaches described here should facilitate the functional analysis of host factors involved in pathogen restriction as well as their mechanisms of regulation.",2019 Mar 14,"['Spence, Jennifer S.', 'He, Ruina', 'Hoffmann, Hans-Heinrich', 'Das, Tandrila', 'Thinon, Emmanuelle', 'Rice, Charles M.', 'Peng, Tao', 'Chandran, Kartik', 'Hang, Howard C.']",Nat Chem Biol,,,False
cd12db30cf8d039ec120a0766259d9311d9a466d,PMC,"Estimating Risk to Responders Exposed to Avian Influenza A H5 and H7 Viruses in Poultry, United States, 2014–2017",http://dx.doi.org/10.3201/eid2505.181253,PMC6478193,30741630,NO-CC CODE,"In the United States, outbreaks of avian influenza H5 and H7 virus infections in poultry have raised concern about the risk for infections in humans. We reviewed the data collected during 2014–2017 and found no human infections among 4,555 exposed responders who were wearing protection.",2019 May,"['Olsen, Sonja J.', 'Rooney, Jane A.', 'Blanton, Lenee', 'Rolfes, Melissa A.', 'Nelson, Deborah I.', 'Gomez, Thomas M.', 'Karli, Steven A.', 'Trock, Susan C.', 'Fry, Alicia M.']",Emerg Infect Dis,,,True
8762e3de42e45d93aebb675328dd466f8be23cf2,PMC,Southeast Asia Strategic Multilateral Dialogue on Biosecurity,http://dx.doi.org/10.3201/eid2505.181659,PMC6478199,31002062,NO-CC CODE,"A strategic multilateral dialogue related to biosecurity risks in Southeast Asia, established in 2014, now includes participants from Singapore, Malaysia, Indonesia, Thailand, Philippines, and the United States. This dialogue is conducted at the nonministerial level, enabling participants to engage without the constraints of operating in their official capacities. Participants reflect on mechanisms to detect, mitigate, and respond to biosecurity risks and highlight biosecurity issues for national leadership. Participants have also identified factors to improve regional and global biosecurity, including improved engagement and collaboration across relevant ministries and agencies, sustainable funding for biosecurity programs, enhanced information sharing for communicable diseases, and increased engagement in international biosecurity forums.",2019 May,"['Cicero, Anita', 'Meyer, Diane', 'Shearer, Matthew P.', 'AbuBakar, Sazaly', 'Bernard, Ken', 'Carus, W. Seth', 'Chong, Chee Kheong', 'Fischer, Julie', 'Hynes, Noreen', 'Inglesby, Tom', 'Kwa, Chong Guan', 'Makalinao, Irma', 'Pangestu, Tikki', 'Sitompul, Ratna', 'Soebandrio, Amin', 'Sudarmono, Pratiwi', 'Tjen, Daniel', 'Wibulpolprasert, Suwit', 'Yunus, Zalini']",Emerg Infect Dis,,,True
77ce90d3ef2d8657d97d027f8e14d7e025b8dc2a,PMC,Southeast Asia Strategic Multilateral Dialogue on Biosecurity,http://dx.doi.org/10.3201/eid2505.181659,PMC6478199,31002062,NO-CC CODE,"A strategic multilateral dialogue related to biosecurity risks in Southeast Asia, established in 2014, now includes participants from Singapore, Malaysia, Indonesia, Thailand, Philippines, and the United States. This dialogue is conducted at the nonministerial level, enabling participants to engage without the constraints of operating in their official capacities. Participants reflect on mechanisms to detect, mitigate, and respond to biosecurity risks and highlight biosecurity issues for national leadership. Participants have also identified factors to improve regional and global biosecurity, including improved engagement and collaboration across relevant ministries and agencies, sustainable funding for biosecurity programs, enhanced information sharing for communicable diseases, and increased engagement in international biosecurity forums.",2019 May,"['Cicero, Anita', 'Meyer, Diane', 'Shearer, Matthew P.', 'AbuBakar, Sazaly', 'Bernard, Ken', 'Carus, W. Seth', 'Chong, Chee Kheong', 'Fischer, Julie', 'Hynes, Noreen', 'Inglesby, Tom', 'Kwa, Chong Guan', 'Makalinao, Irma', 'Pangestu, Tikki', 'Sitompul, Ratna', 'Soebandrio, Amin', 'Sudarmono, Pratiwi', 'Tjen, Daniel', 'Wibulpolprasert, Suwit', 'Yunus, Zalini']",Emerg Infect Dis,,,False
5ccde00be19e522ea42e8198124df31de00f6afb,PMC,"Biosafety Level 4 Laboratory User Training Program, China",http://dx.doi.org/10.3201/eid2505.180220,PMC6478205,31002302,NO-CC CODE,"Experienced, qualified personnel certified to work in high-level biocontainment laboratories contribute to the safe operation of these facilities. China began a training program for laboratory users after establishing its first Biosafety Level 4 laboratory, the Wuhan National Biosafety Laboratory (Level 4) of the Chinese Academy of Sciences. We provide an overview of the content of this training program, which can serve as a reference for developing national norms for high-containment laboratory training.",2019 May,"['Xia, Han', 'Huang, Yi', 'Ma, Haixia', 'Liu, Bobo', 'Xie, Weiwei', 'Song, Donglin', 'Yuan, Zhiming']",Emerg Infect Dis,,,True
983e4e747ad0691e47cb54ed407a014f66f96380,PMC,"Genetic Characterization of Middle East Respiratory Syndrome Coronavirus, South Korea, 2018",http://dx.doi.org/10.3201/eid2505.181534,PMC6478226,30753126,NO-CC CODE,"We evaluated genetic variation in Middle East respiratory syndrome coronavirus (MERS-CoV) imported to South Korea in 2018 using specimens from a patient and isolates from infected Caco-2 cells. The MERS-CoV strain in this study was genetically similar to a strain isolated in Riyadh, Saudi Arabia, in 2017.",2019 May,"['Chung, Yoon-Seok', 'Kim, Jeong Min', 'Man Kim, Heui', 'Park, Kye Ryeong', 'Lee, Anna', 'Lee, Nam-Joo', 'Kim, Mi-Seon', 'Kim, Jun Sub', 'Kim, Chi-Kyeong', 'Lee, Jae In', 'Kang, Chun']",Emerg Infect Dis,,,True
44a3cf460f8ce1edf8df41d96242735398773acd,PMC,"Risk Factors for MERS-CoV Seropositivity among Animal Market and Slaughterhouse Workers, Abu Dhabi, United Arab Emirates, 2014–2017",http://dx.doi.org/10.3201/eid2505.181728,PMC6478233,31002068,NO-CC CODE,"Camel contact is a recognized risk factor for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Because specific camel exposures associated with MERS-CoV seropositivity are not fully understood, we investigated worker–camel interactions and MERS-CoV seroprevalence. We assessed worker seroprevalence in 2 slaughterhouses and 1 live-animal market in Abu Dhabi, United Arab Emirates, during 2014–2017 and administered an epidemiologic survey in 2016 and 2017. Across 3 sampling rounds during 2014–2017, we sampled 100–235 workers, and 6%–19% were seropositive for MERS-CoV at each sampling round. One (1.4%) of 70 seronegative workers tested at multiple rounds seroconverted. On multivariable analyses, working as a camel salesman, handling live camels or their waste, and having diabetes were associated with seropositivity among all workers, whereas handling live camels and either administering medications or cleaning equipment was associated with seropositivity among market workers. Characterization of high-risk exposures is critical for implementation of preventive measures.",2019 May,"['Khudhair, Ahmed', 'Killerby, Marie E.', 'Al Mulla, Mariam', 'Abou Elkheir, Kheir', 'Ternanni, Wassim', 'Bandar, Zyad', 'Weber, Stefan', 'Khoury, Mary', 'Donnelly, George', 'Al Muhairi, Salama', 'Khalafalla, Abdelmalik I.', 'Trivedi, Suvang', 'Tamin, Azaibi', 'Thornburg, Natalie J.', 'Watson, John T.', 'Gerber, Susan I.', 'Al Hosani, Farida', 'Hall, Aron J.']",Emerg Infect Dis,,,True
23e37229a4f38c5649f2d34a87509aec4b772c37,PMC,"Risk Factors for MERS-CoV Seropositivity among Animal Market and Slaughterhouse Workers, Abu Dhabi, United Arab Emirates, 2014–2017",http://dx.doi.org/10.3201/eid2505.181728,PMC6478233,31002068,NO-CC CODE,"Camel contact is a recognized risk factor for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Because specific camel exposures associated with MERS-CoV seropositivity are not fully understood, we investigated worker–camel interactions and MERS-CoV seroprevalence. We assessed worker seroprevalence in 2 slaughterhouses and 1 live-animal market in Abu Dhabi, United Arab Emirates, during 2014–2017 and administered an epidemiologic survey in 2016 and 2017. Across 3 sampling rounds during 2014–2017, we sampled 100–235 workers, and 6%–19% were seropositive for MERS-CoV at each sampling round. One (1.4%) of 70 seronegative workers tested at multiple rounds seroconverted. On multivariable analyses, working as a camel salesman, handling live camels or their waste, and having diabetes were associated with seropositivity among all workers, whereas handling live camels and either administering medications or cleaning equipment was associated with seropositivity among market workers. Characterization of high-risk exposures is critical for implementation of preventive measures.",2019 May,"['Khudhair, Ahmed', 'Killerby, Marie E.', 'Al Mulla, Mariam', 'Abou Elkheir, Kheir', 'Ternanni, Wassim', 'Bandar, Zyad', 'Weber, Stefan', 'Khoury, Mary', 'Donnelly, George', 'Al Muhairi, Salama', 'Khalafalla, Abdelmalik I.', 'Trivedi, Suvang', 'Tamin, Azaibi', 'Thornburg, Natalie J.', 'Watson, John T.', 'Gerber, Susan I.', 'Al Hosani, Farida', 'Hall, Aron J.']",Emerg Infect Dis,,,False
ca1257a05c3a1c56ac4d806a2e4ba16ba983b793,PMC,"Risk Factors for MERS-CoV Seropositivity among Animal Market and Slaughterhouse Workers, Abu Dhabi, United Arab Emirates, 2014–2017",http://dx.doi.org/10.3201/eid2505.181728,PMC6478233,31002068,NO-CC CODE,"Camel contact is a recognized risk factor for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Because specific camel exposures associated with MERS-CoV seropositivity are not fully understood, we investigated worker–camel interactions and MERS-CoV seroprevalence. We assessed worker seroprevalence in 2 slaughterhouses and 1 live-animal market in Abu Dhabi, United Arab Emirates, during 2014–2017 and administered an epidemiologic survey in 2016 and 2017. Across 3 sampling rounds during 2014–2017, we sampled 100–235 workers, and 6%–19% were seropositive for MERS-CoV at each sampling round. One (1.4%) of 70 seronegative workers tested at multiple rounds seroconverted. On multivariable analyses, working as a camel salesman, handling live camels or their waste, and having diabetes were associated with seropositivity among all workers, whereas handling live camels and either administering medications or cleaning equipment was associated with seropositivity among market workers. Characterization of high-risk exposures is critical for implementation of preventive measures.",2019 May,"['Khudhair, Ahmed', 'Killerby, Marie E.', 'Al Mulla, Mariam', 'Abou Elkheir, Kheir', 'Ternanni, Wassim', 'Bandar, Zyad', 'Weber, Stefan', 'Khoury, Mary', 'Donnelly, George', 'Al Muhairi, Salama', 'Khalafalla, Abdelmalik I.', 'Trivedi, Suvang', 'Tamin, Azaibi', 'Thornburg, Natalie J.', 'Watson, John T.', 'Gerber, Susan I.', 'Al Hosani, Farida', 'Hall, Aron J.']",Emerg Infect Dis,,,False
a7517a8506234e015417206358feca31adbf21a2,PMC,PLANT-Dx: A Molecular Diagnostic for Point-of-Use Detection of Plant Pathogens,http://dx.doi.org/10.1021/acssynbio.8b00526,PMC6479721,30790518,NO-CC CODE,"[Image: see text] Synthetic biology based diagnostic technologies have improved upon gold standard diagnostic methodologies by decreasing cost, increasing accuracy, and enhancing portability. However, there has been little effort in adapting these technologies toward applications related to point-of-use monitoring of plant and crop health. Here, we take a step toward this vision by developing an approach that couples isothermal amplification of specific plant pathogen genomic sequences with customizable synthetic RNA regulators that are designed to trigger the production of a colorimetric output in cell-free gene expression reactions. We demonstrate our system can sense viral derived sequences with high sensitivity and specificity, and can be utilized to directly detect viruses from infected plant material. Furthermore, we demonstrate that the entire system can operate using only body heat and naked-eye visual analysis of outputs. We anticipate these strategies to be important components of user-friendly and deployable diagnostic systems that can be configured to detect a range of important plant pathogens.",2019 Apr 19,"['Verosloff, M.', 'Chappell, J.', 'Perry, K. L.', 'Thompson, J. R.', 'Lucks, J. B.']",ACS Synth Biol,,,True
4b7bc42834fed4d8fc2ea5446649bec17fddb81a,PMC,PLANT-Dx: A Molecular Diagnostic for Point-of-Use Detection of Plant Pathogens,http://dx.doi.org/10.1021/acssynbio.8b00526,PMC6479721,30790518,NO-CC CODE,"[Image: see text] Synthetic biology based diagnostic technologies have improved upon gold standard diagnostic methodologies by decreasing cost, increasing accuracy, and enhancing portability. However, there has been little effort in adapting these technologies toward applications related to point-of-use monitoring of plant and crop health. Here, we take a step toward this vision by developing an approach that couples isothermal amplification of specific plant pathogen genomic sequences with customizable synthetic RNA regulators that are designed to trigger the production of a colorimetric output in cell-free gene expression reactions. We demonstrate our system can sense viral derived sequences with high sensitivity and specificity, and can be utilized to directly detect viruses from infected plant material. Furthermore, we demonstrate that the entire system can operate using only body heat and naked-eye visual analysis of outputs. We anticipate these strategies to be important components of user-friendly and deployable diagnostic systems that can be configured to detect a range of important plant pathogens.",2019 Apr 19,"['Verosloff, M.', 'Chappell, J.', 'Perry, K. L.', 'Thompson, J. R.', 'Lucks, J. B.']",ACS Synth Biol,,,True
b277e521eb43fedeb50a08be126e76dd9bc7314a,PMC,"Highly Pathogenic Swine Getah Virus in Blue Foxes, Eastern China, 2017",http://dx.doi.org/10.3201/eid2506.181983,PMC6537705,31107236,NO-CC CODE,"We isolated Getah virus from infected foxes in Shandong Province, eastern China. We sequenced the complete Getah virus genome, and phylogenetic analysis revealed a close relationship with a highly pathogenic swine epidemic strain in China. Epidemiologic investigation showed that pigs might play a pivotal role in disease transmission to foxes.",2019 Jun,"['Shi, Ning', 'Li, Li-Xia', 'Lu, Rong-Guang', 'Yan, Xi-Jun', 'Liu, Hao']",Emerg Infect Dis,,,True
d7f0833fec517664476dec5be59b0b9fbf4ed225,PMC,"Highly Pathogenic Swine Getah Virus in Blue Foxes, Eastern China, 2017",http://dx.doi.org/10.3201/eid2506.181983,PMC6537705,31107236,NO-CC CODE,"We isolated Getah virus from infected foxes in Shandong Province, eastern China. We sequenced the complete Getah virus genome, and phylogenetic analysis revealed a close relationship with a highly pathogenic swine epidemic strain in China. Epidemiologic investigation showed that pigs might play a pivotal role in disease transmission to foxes.",2019 Jun,"['Shi, Ning', 'Li, Li-Xia', 'Lu, Rong-Guang', 'Yan, Xi-Jun', 'Liu, Hao']",Emerg Infect Dis,,,False
11e93497dd9355cd46dadf58d09c331585f0b6cf,PMC,"Respiratory Syncytial Virus Seasonality, Beijing, China, 2007–2015",http://dx.doi.org/10.3201/eid2506.180532,PMC6537707,31107230,NO-CC CODE,"During July 2007–June 2015, we enrolled 4,225 hospitalized children with pneumonia in a study to determine the seasonality of respiratory syncytial virus (RSV) infection in Beijing, China. We defined season as the period during which >10% of total PCRs performed each week were RSV positive. We identified 8 distinctive RSV seasons. On average, the season onset occurred at week 41 (mid-October) and lasted 33 weeks, through week 20 of the next year (mid-May); 97% of all RSV-positive cases occurred during the season. RSV seasons occurred 3–5 weeks earlier and lasted ≈6 weeks longer in RSV subgroup A–dominant years than in RSV subgroup B–dominant years. Our analysis indicates that monitoring such RSV subgroup shifts might provide better estimates for the onset of RSV transmission. PCR-based tests could be a flexible or complementary way of determining RSV seasonality in locations where RSV surveillance is less well-established, such as local hospitals throughout China.",2019 Jun,"['Yu, Jianxing', 'Liu, Chunyan', 'Xiao, Yan', 'Xiang, Zichun', 'Zhou, Hongli', 'Chen, Lan', 'Shen, Kunling', 'Xie, Zhengde', 'Ren, Lili', 'Wang, Jianwei']",Emerg Infect Dis,,,True
5c8b5beacab1ef316ed826f261d23c87e033a928,PMC,"Molecular Evidence of Human Monkeypox Virus Infection, Sierra Leone",http://dx.doi.org/10.3201/eid2506.180296,PMC6537715,30900976,NO-CC CODE,"Monkeypox virus is a zoonotic disease endemic to Africa. In 2017, we confirmed a case of human monkeypox virus in Sierra Leone by molecular and serologic methods. Sequencing analysis indicated the virus belongs to the West African clade and data suggest it was likely transmitted by wild animals.",2019 Jun,"['Ye, Fei', 'Song, Jingdong', 'Zhao, Li', 'Zhang, Yi', 'Xia, Lianxu', 'Zhu, Lingwei', 'Kamara, Idrissa Laybohr', 'Ren, Jiao', 'Wang, Wenling', 'Tian, Houwen', 'Wu, Guizhen', 'Tan, Wenjie']",Emerg Infect Dis,,,True
acf494aa494ba8b7adcc7073535230c9db7b4e2d,PMC,"Molecular Evidence of Human Monkeypox Virus Infection, Sierra Leone",http://dx.doi.org/10.3201/eid2506.180296,PMC6537715,30900976,NO-CC CODE,"Monkeypox virus is a zoonotic disease endemic to Africa. In 2017, we confirmed a case of human monkeypox virus in Sierra Leone by molecular and serologic methods. Sequencing analysis indicated the virus belongs to the West African clade and data suggest it was likely transmitted by wild animals.",2019 Jun,"['Ye, Fei', 'Song, Jingdong', 'Zhao, Li', 'Zhang, Yi', 'Xia, Lianxu', 'Zhu, Lingwei', 'Kamara, Idrissa Laybohr', 'Ren, Jiao', 'Wang, Wenling', 'Tian, Houwen', 'Wu, Guizhen', 'Tan, Wenjie']",Emerg Infect Dis,,,False
1fd44d22a387ba56fd367ceb0737762e9ee9d5cb,PMC,"Sequential Emergence and Wide Spread of Neutralization Escape Middle East Respiratory Syndrome Coronavirus Mutants, South Korea, 2015",http://dx.doi.org/10.3201/eid2506.181722,PMC6537729,30900977,NO-CC CODE,"The unexpectedly large outbreak of Middle East respiratory syndrome in South Korea in 2015 was initiated by an infected traveler and amplified by several “superspreading” events. Previously, we reported the emergence and spread of mutant Middle East respiratory syndrome coronavirus bearing spike mutations (I529T or D510G) with reduced affinity to human receptor CD26 during the outbreak. To assess the potential association of spike mutations with superspreading events, we collected virus genetic information reported during the outbreak and systemically analyzed the relationship of spike sequences and epidemiology. We found sequential emergence of the spike mutations in 2 superspreaders. In vivo virulence of the mutant viruses seems to decline in human patients, as assessed by fever duration in affected persons. In addition, neutralizing activity against these 2 mutant viruses in serum samples from mice immunized with wild-type spike antigen were gradually reduced, suggesting emergence and wide spread of neutralization escapers during the outbreak.",2019 Jun,"['Kim, Yeon-Sook', 'Aigerim, Abdimadiyeva', 'Park, Uni', 'Kim, Yuri', 'Rhee, Ji-Young', 'Choi, Jae-Phil', 'Park, Wan Beom', 'Park, Sang Won', 'Kim, Yeonjae', 'Lim, Dong-Gyun', 'Inn, Kyung-Soo', 'Hwang, Eung-Soo', 'Choi, Myung-Sik', 'Shin, Hyoung-Shik', 'Cho, Nam-Hyuk']",Emerg Infect Dis,,,True
14ec024c18ac73f9f5c859853acf801887aa9ef0,PMC,"Sequential Emergence and Wide Spread of Neutralization Escape Middle East Respiratory Syndrome Coronavirus Mutants, South Korea, 2015",http://dx.doi.org/10.3201/eid2506.181722,PMC6537729,30900977,NO-CC CODE,"The unexpectedly large outbreak of Middle East respiratory syndrome in South Korea in 2015 was initiated by an infected traveler and amplified by several “superspreading” events. Previously, we reported the emergence and spread of mutant Middle East respiratory syndrome coronavirus bearing spike mutations (I529T or D510G) with reduced affinity to human receptor CD26 during the outbreak. To assess the potential association of spike mutations with superspreading events, we collected virus genetic information reported during the outbreak and systemically analyzed the relationship of spike sequences and epidemiology. We found sequential emergence of the spike mutations in 2 superspreaders. In vivo virulence of the mutant viruses seems to decline in human patients, as assessed by fever duration in affected persons. In addition, neutralizing activity against these 2 mutant viruses in serum samples from mice immunized with wild-type spike antigen were gradually reduced, suggesting emergence and wide spread of neutralization escapers during the outbreak.",2019 Jun,"['Kim, Yeon-Sook', 'Aigerim, Abdimadiyeva', 'Park, Uni', 'Kim, Yuri', 'Rhee, Ji-Young', 'Choi, Jae-Phil', 'Park, Wan Beom', 'Park, Sang Won', 'Kim, Yeonjae', 'Lim, Dong-Gyun', 'Inn, Kyung-Soo', 'Hwang, Eung-Soo', 'Choi, Myung-Sik', 'Shin, Hyoung-Shik', 'Cho, Nam-Hyuk']",Emerg Infect Dis,,,True
b9b56a7b507acbddb2122ecc330a8d331c5ff33c,PMC,"Influenza D Virus Infection in Dromedary Camels, Ethiopia",http://dx.doi.org/10.3201/eid2506.181158,PMC6537730,31107233,NO-CC CODE,"Influenza D virus has been found to cause respiratory diseases in livestock. We surveyed healthy dromedary camels in Ethiopia and found a high seroprevalence for this virus, in contrast to animals co-existing with the camels. Our observation implies that dromedary camels may play an important role in the circulation of influenza D virus.",2019 Jun,"['Murakami, Shin', 'Odagiri, Tomoha', 'Melaku, Simenew Keskes', 'Bazartseren, Boldbaatar', 'Ishida, Hiroho', 'Takenaka-Uema, Akiko', 'Muraki, Yasushi', 'Sentsui, Hiroshi', 'Horimoto, Taisuke']",Emerg Infect Dis,,,True
b9af3af1200aa20fad1e74f18d971c840b25f595,PMC,"Correction: Vol. 25, No. 5",http://dx.doi.org/10.3201/eid2506.C12506,PMC6537737,,NO-CC CODE,,2019 Jun,,Emerg Infect Dis,,,False
f6323e7d11e94480fdd62e5caad023d4d2d7cf6d,PMC,Structural basis for human coronavirus attachment to sialic acid receptors,http://dx.doi.org/10.1038/s41594-019-0233-y,PMC6554059,31160783,NO-CC CODE,"Coronaviruses cause respiratory tract infections in humans and outbreaks of deadly pneumonia worldwide. Infections are initiated by the transmembrane spike (S) glycoprotein, which binds to host receptors and fuses the viral and cellular membranes. To understand the molecular basis of coronavirus attachment to oligosaccharide receptors, we determined cryo-EM structures of coronavirus OC43 S glycoprotein trimer in isolation and in complex with a 9-O-acetylated sialic acid. We demonstrate that the ligand binds with fast kinetics to a surface-exposed groove and interactions at the identified site are essential for S-mediated viral entry into host cells, but free monosaccharide did not trigger fusogenic conformational changes. The receptor-interacting site is conserved in all coronavirus S glycoproteins that engage 9-O-acetyl-sialogycans, with an architecture similar to the ligand-binding pockets of coronavirus hemagglutinin esterases and influenza virus C/D hemagglutinin-esterase-fusion glycoproteins. Our results demonstrate these viruses evolved similar strategies to engage sialoglycans at the surface of target cells.",2019 Jun 3,"['Tortorici, M. Alejandra', 'Walls, Alexandra C.', 'Lang, Yifei', 'Wang, Chunyan', 'Li, Zeshi', 'Koerhuis, Danielle', 'Boons, Geert-Jan', 'Bosch, Berend-Jan', 'Rey, Félix A.', 'de Groot, Raoul J.', 'Veesler, David']",Nat Struct Mol Biol,,,True
f655ed958a5ba1036a9fa2ef6d370829d6ec8b9b,PMC,Capturing sequence diversity in metagenomes with comprehensive and scalable probe design,http://dx.doi.org/10.1038/s41587-018-0006-x,PMC6587591,30718881,NO-CC CODE,"Metagenomic sequencing has the potential to transform microbial detection and characterization, but new tools are needed to improve its sensitivity. Here we present CATCH, a computational method to enhance nucleic-acid capture for enrichment of diverse microbial taxa. CATCH designs optimal probe sets, with a specified number of oligonucleotides, that achieve full coverage of and scale well with known sequence diversity. We focus on applying CATCH to capture viral genomes in complex metagenomic samples. We design, synthesize, and validate multiple probe sets, including one that targets whole genomes of the 356 viral species known to infect humans. Capture with these probe sets enriches unique viral content on average 18-fold, allowing us to assemble genomes that could not be recovered without enrichment, and accurately preserves within-sample diversity. We also use these probe sets to recover genomes from the 2018 Lassa fever outbreak in Nigeria and to improve detection of uncharacterized viral infections in human and mosquito samples. The results demonstrate that CATCH enables more sensitive and cost-effective metagenomic sequencing.",2019 Feb 4,"['Metsky, Hayden C.', 'Siddle, Katherine J.', 'Gladden-Young, Adrianne', 'Qu, James', 'Yang, David K.', 'Brehio, Patrick', 'Goldfarb, Andrew', 'Piantadosi, Anne', 'Wohl, Shirlee', 'Carter, Amber', 'Lin, Aaron E.', 'Barnes, Kayla G.', 'Tully, Damien C.', 'Corleis, Bjӧrn', 'Hennigan, Scott', 'Barbosa-Lima, Giselle', 'Vieira, Yasmine R.', 'Paul, Lauren M.', 'Tan, Amanda L.', 'Garcia, Kimberly F.', 'Parham, Leda A.', 'Odia, Ikponmwosa', 'Eromon, Philomena', 'Folarin, Onikepe A.', 'Goba, Augustine', None, 'Simon-Lorière, Etienne', 'Hensley, Lisa', 'Balmaseda, Angel', 'Harris, Eva', 'Kwon, Douglas S.', 'Allen, Todd M.', 'Runstadler, Jonathan A.', 'Smole, Sandra', 'Bozza, Fernando A.', 'Souza, Thiago M. L.', 'Isern, Sharon', 'Michael, Scott F.', 'Lorenzana, Ivette', 'Gehrke, Lee', 'Bosch, Irene', 'Ebel, Gregory', 'Grant, Donald S.', 'Happi, Christian T.', 'Park, Daniel J.', 'Gnirke, Andreas', 'Sabeti, Pardis C.', 'Matranga, Christian B.']",Nat Biotechnol,,,True
d17520ab15c1b95cc544c2baad74e71d669c188e,PMC,Capturing sequence diversity in metagenomes with comprehensive and scalable probe design,http://dx.doi.org/10.1038/s41587-018-0006-x,PMC6587591,30718881,NO-CC CODE,"Metagenomic sequencing has the potential to transform microbial detection and characterization, but new tools are needed to improve its sensitivity. Here we present CATCH, a computational method to enhance nucleic-acid capture for enrichment of diverse microbial taxa. CATCH designs optimal probe sets, with a specified number of oligonucleotides, that achieve full coverage of and scale well with known sequence diversity. We focus on applying CATCH to capture viral genomes in complex metagenomic samples. We design, synthesize, and validate multiple probe sets, including one that targets whole genomes of the 356 viral species known to infect humans. Capture with these probe sets enriches unique viral content on average 18-fold, allowing us to assemble genomes that could not be recovered without enrichment, and accurately preserves within-sample diversity. We also use these probe sets to recover genomes from the 2018 Lassa fever outbreak in Nigeria and to improve detection of uncharacterized viral infections in human and mosquito samples. The results demonstrate that CATCH enables more sensitive and cost-effective metagenomic sequencing.",2019 Feb 4,"['Metsky, Hayden C.', 'Siddle, Katherine J.', 'Gladden-Young, Adrianne', 'Qu, James', 'Yang, David K.', 'Brehio, Patrick', 'Goldfarb, Andrew', 'Piantadosi, Anne', 'Wohl, Shirlee', 'Carter, Amber', 'Lin, Aaron E.', 'Barnes, Kayla G.', 'Tully, Damien C.', 'Corleis, Bjӧrn', 'Hennigan, Scott', 'Barbosa-Lima, Giselle', 'Vieira, Yasmine R.', 'Paul, Lauren M.', 'Tan, Amanda L.', 'Garcia, Kimberly F.', 'Parham, Leda A.', 'Odia, Ikponmwosa', 'Eromon, Philomena', 'Folarin, Onikepe A.', 'Goba, Augustine', None, 'Simon-Lorière, Etienne', 'Hensley, Lisa', 'Balmaseda, Angel', 'Harris, Eva', 'Kwon, Douglas S.', 'Allen, Todd M.', 'Runstadler, Jonathan A.', 'Smole, Sandra', 'Bozza, Fernando A.', 'Souza, Thiago M. L.', 'Isern, Sharon', 'Michael, Scott F.', 'Lorenzana, Ivette', 'Gehrke, Lee', 'Bosch, Irene', 'Ebel, Gregory', 'Grant, Donald S.', 'Happi, Christian T.', 'Park, Daniel J.', 'Gnirke, Andreas', 'Sabeti, Pardis C.', 'Matranga, Christian B.']",Nat Biotechnol,,,False
66f61883f53c7f49e831833a50c7d37858250cfe,PMC,Capturing sequence diversity in metagenomes with comprehensive and scalable probe design,http://dx.doi.org/10.1038/s41587-018-0006-x,PMC6587591,30718881,NO-CC CODE,"Metagenomic sequencing has the potential to transform microbial detection and characterization, but new tools are needed to improve its sensitivity. Here we present CATCH, a computational method to enhance nucleic-acid capture for enrichment of diverse microbial taxa. CATCH designs optimal probe sets, with a specified number of oligonucleotides, that achieve full coverage of and scale well with known sequence diversity. We focus on applying CATCH to capture viral genomes in complex metagenomic samples. We design, synthesize, and validate multiple probe sets, including one that targets whole genomes of the 356 viral species known to infect humans. Capture with these probe sets enriches unique viral content on average 18-fold, allowing us to assemble genomes that could not be recovered without enrichment, and accurately preserves within-sample diversity. We also use these probe sets to recover genomes from the 2018 Lassa fever outbreak in Nigeria and to improve detection of uncharacterized viral infections in human and mosquito samples. The results demonstrate that CATCH enables more sensitive and cost-effective metagenomic sequencing.",2019 Feb 4,"['Metsky, Hayden C.', 'Siddle, Katherine J.', 'Gladden-Young, Adrianne', 'Qu, James', 'Yang, David K.', 'Brehio, Patrick', 'Goldfarb, Andrew', 'Piantadosi, Anne', 'Wohl, Shirlee', 'Carter, Amber', 'Lin, Aaron E.', 'Barnes, Kayla G.', 'Tully, Damien C.', 'Corleis, Bjӧrn', 'Hennigan, Scott', 'Barbosa-Lima, Giselle', 'Vieira, Yasmine R.', 'Paul, Lauren M.', 'Tan, Amanda L.', 'Garcia, Kimberly F.', 'Parham, Leda A.', 'Odia, Ikponmwosa', 'Eromon, Philomena', 'Folarin, Onikepe A.', 'Goba, Augustine', None, 'Simon-Lorière, Etienne', 'Hensley, Lisa', 'Balmaseda, Angel', 'Harris, Eva', 'Kwon, Douglas S.', 'Allen, Todd M.', 'Runstadler, Jonathan A.', 'Smole, Sandra', 'Bozza, Fernando A.', 'Souza, Thiago M. L.', 'Isern, Sharon', 'Michael, Scott F.', 'Lorenzana, Ivette', 'Gehrke, Lee', 'Bosch, Irene', 'Ebel, Gregory', 'Grant, Donald S.', 'Happi, Christian T.', 'Park, Daniel J.', 'Gnirke, Andreas', 'Sabeti, Pardis C.', 'Matranga, Christian B.']",Nat Biotechnol,,,False
8711aed56f3656289b66b987d669c3228977a60f,PMC,Capturing sequence diversity in metagenomes with comprehensive and scalable probe design,http://dx.doi.org/10.1038/s41587-018-0006-x,PMC6587591,30718881,NO-CC CODE,"Metagenomic sequencing has the potential to transform microbial detection and characterization, but new tools are needed to improve its sensitivity. Here we present CATCH, a computational method to enhance nucleic-acid capture for enrichment of diverse microbial taxa. CATCH designs optimal probe sets, with a specified number of oligonucleotides, that achieve full coverage of and scale well with known sequence diversity. We focus on applying CATCH to capture viral genomes in complex metagenomic samples. We design, synthesize, and validate multiple probe sets, including one that targets whole genomes of the 356 viral species known to infect humans. Capture with these probe sets enriches unique viral content on average 18-fold, allowing us to assemble genomes that could not be recovered without enrichment, and accurately preserves within-sample diversity. We also use these probe sets to recover genomes from the 2018 Lassa fever outbreak in Nigeria and to improve detection of uncharacterized viral infections in human and mosquito samples. The results demonstrate that CATCH enables more sensitive and cost-effective metagenomic sequencing.",2019 Feb 4,"['Metsky, Hayden C.', 'Siddle, Katherine J.', 'Gladden-Young, Adrianne', 'Qu, James', 'Yang, David K.', 'Brehio, Patrick', 'Goldfarb, Andrew', 'Piantadosi, Anne', 'Wohl, Shirlee', 'Carter, Amber', 'Lin, Aaron E.', 'Barnes, Kayla G.', 'Tully, Damien C.', 'Corleis, Bjӧrn', 'Hennigan, Scott', 'Barbosa-Lima, Giselle', 'Vieira, Yasmine R.', 'Paul, Lauren M.', 'Tan, Amanda L.', 'Garcia, Kimberly F.', 'Parham, Leda A.', 'Odia, Ikponmwosa', 'Eromon, Philomena', 'Folarin, Onikepe A.', 'Goba, Augustine', None, 'Simon-Lorière, Etienne', 'Hensley, Lisa', 'Balmaseda, Angel', 'Harris, Eva', 'Kwon, Douglas S.', 'Allen, Todd M.', 'Runstadler, Jonathan A.', 'Smole, Sandra', 'Bozza, Fernando A.', 'Souza, Thiago M. L.', 'Isern, Sharon', 'Michael, Scott F.', 'Lorenzana, Ivette', 'Gehrke, Lee', 'Bosch, Irene', 'Ebel, Gregory', 'Grant, Donald S.', 'Happi, Christian T.', 'Park, Daniel J.', 'Gnirke, Andreas', 'Sabeti, Pardis C.', 'Matranga, Christian B.']",Nat Biotechnol,,,True
90dc562112c5255333e45785fbf77a39fb1ef4cb,PMC,Complete Genome Sequence of a Severe Acute Respiratory Syndrome-Related Coronavirus from Kenyan Bats,http://dx.doi.org/10.1128/MRA.00548-19,PMC6624766,31296683,NO-CC CODE,"We identified a strain of betacoronavirus BtKY72/Rhinolophus sp./Kenya/2007 (here BtKY72) from rectal swab samples in Kenyan bats. This paper reports the complete genomic sequence of BtKY72, which is closely related to BtCoV/BM48-31/Bulgaria/2008, a severe acute respiratory syndrome (SARS)-related virus from Rhinolophus bats in Europe.",2019 Jul 11,"['Tao, Ying', 'Tong, Suxiang']",Microbiol Resour Announc,,,True
74f8669398e63312feb0b386234ce36ee8d873f6,PMC,Highly Efficient and Practical N-Heterocyclic Carbene Organocatalyzed Chemoselective N(1)/C(3)-Functionalization of Isatins with Green Chemistry Principles,http://dx.doi.org/10.1021/acsomega.8b02361,PMC6643579,31458364,NO-CC CODE,"[Image: see text] Ecofriendly N-heterocyclic carbene (NHC) organocatalysis can control the N(1)-functionalization (aza-Michael addition) and C(3)-functionalization (Morita–Baylis–Hillman reaction, MBH) of isatins in the absence of (1) a protecting group, (2) a stoichiometric reagent, and (3) heat energy. The challengeable N(1)-functionalization of N-unsubstituted isatins into N-substituted (NS) isatins was realized through 10 mol % NHC and 10 mol % 1,8-diazabicyclo[5.4.0]undec-7-ene catalysts within 10 min with up to 98% isolation yield. The subsequent MBH adducts of as-synthesized NS-isatins (N(1)/C(3)-functionalization) was perfectly acquired in 10 mol % NHC and 10 mol % 1,4-diazabicyclo[2.2.2]octane catalysis within 30 min with superiority to C(3)/N(1)-functionalization (MBH/aza-Michael). For guiding the application to a versatile druggable isatin library, the NHC catalysis was compared with reported functionalization of isatins in view of green chemistry principles including solvent scoring of ACS GCI pharmaceutical roundtable, E-factor, atom economy, and so on.",2018 Dec 18,"['Mudithanapelli, Chandrashekar', 'Vasam, Chandra Sekhar', 'Vadde, Ravinder', 'Kim, Mi-hyun']",ACS Omega,,,True
3eb27a4a8fe46f979c80da67e044c3d7042a5ec6,PMC,Highly Efficient and Practical N-Heterocyclic Carbene Organocatalyzed Chemoselective N(1)/C(3)-Functionalization of Isatins with Green Chemistry Principles,http://dx.doi.org/10.1021/acsomega.8b02361,PMC6643579,31458364,NO-CC CODE,"[Image: see text] Ecofriendly N-heterocyclic carbene (NHC) organocatalysis can control the N(1)-functionalization (aza-Michael addition) and C(3)-functionalization (Morita–Baylis–Hillman reaction, MBH) of isatins in the absence of (1) a protecting group, (2) a stoichiometric reagent, and (3) heat energy. The challengeable N(1)-functionalization of N-unsubstituted isatins into N-substituted (NS) isatins was realized through 10 mol % NHC and 10 mol % 1,8-diazabicyclo[5.4.0]undec-7-ene catalysts within 10 min with up to 98% isolation yield. The subsequent MBH adducts of as-synthesized NS-isatins (N(1)/C(3)-functionalization) was perfectly acquired in 10 mol % NHC and 10 mol % 1,4-diazabicyclo[2.2.2]octane catalysis within 30 min with superiority to C(3)/N(1)-functionalization (MBH/aza-Michael). For guiding the application to a versatile druggable isatin library, the NHC catalysis was compared with reported functionalization of isatins in view of green chemistry principles including solvent scoring of ACS GCI pharmaceutical roundtable, E-factor, atom economy, and so on.",2018 Dec 18,"['Mudithanapelli, Chandrashekar', 'Vasam, Chandra Sekhar', 'Vadde, Ravinder', 'Kim, Mi-hyun']",ACS Omega,,,True
1ebb99d6c23999bab025feddb7a13b81b36d1947,PMC,Structural Analysis of Biomolecules through a Combination of Mobility Capillary Electrophoresis and Mass Spectrometry,http://dx.doi.org/10.1021/acsomega.8b03224,PMC6648644,31459477,NO-CC CODE,"[Image: see text] The 3D structures of biomolecules determine their biological function. Established methods in biomolecule structure determination typically require purification, crystallization, or modification of target molecules, which limits their applications for analyzing trace amounts of biomolecules in complex matrices. Here, we developed instruments and methods of mobility capillary electrophoresis (MCE) and its coupling with MS for the 3D structural analysis of biomolecules in the liquid phase. Biomolecules in complex matrices could be separated by MCE and sequentially detected by MS. The effective radius and the aspect ratio of each separated biomolecule were simultaneously determined through the separation by MCE, which were then used as restraints in determining biomolecule conformations through modeling. Feasibility of this method was verified by analyzing a mixture of somatostatin and bradykinin, two peptides with known liquid-phase structures. Proteins could also be structurally analyzed using this method, which was demonstrated for lysozyme. The combination of MCE and MS for complex sample analysis was also demonstrated. MCE and MCE–MS would allow us to analyze trace amounts of biomolecules in complex matrices, which has the potential to be an alternative and powerful biomolecule structure analysis technique.",2019 Jan 31,"['He, Muyi', 'Luo, Pan', 'Hong, Jie', 'Wang, Xiaofeng', 'Wu, Haimei', 'Zhang, Rongkai', 'Qu, Feng', 'Xiang, Ye', 'Xu, Wei']",ACS Omega,,,True
a73fc4cdae879883ba1f8d2fb4af2b72823dca8d,PMC,Structural Analysis of Biomolecules through a Combination of Mobility Capillary Electrophoresis and Mass Spectrometry,http://dx.doi.org/10.1021/acsomega.8b03224,PMC6648644,31459477,NO-CC CODE,"[Image: see text] The 3D structures of biomolecules determine their biological function. Established methods in biomolecule structure determination typically require purification, crystallization, or modification of target molecules, which limits their applications for analyzing trace amounts of biomolecules in complex matrices. Here, we developed instruments and methods of mobility capillary electrophoresis (MCE) and its coupling with MS for the 3D structural analysis of biomolecules in the liquid phase. Biomolecules in complex matrices could be separated by MCE and sequentially detected by MS. The effective radius and the aspect ratio of each separated biomolecule were simultaneously determined through the separation by MCE, which were then used as restraints in determining biomolecule conformations through modeling. Feasibility of this method was verified by analyzing a mixture of somatostatin and bradykinin, two peptides with known liquid-phase structures. Proteins could also be structurally analyzed using this method, which was demonstrated for lysozyme. The combination of MCE and MS for complex sample analysis was also demonstrated. MCE and MCE–MS would allow us to analyze trace amounts of biomolecules in complex matrices, which has the potential to be an alternative and powerful biomolecule structure analysis technique.",2019 Jan 31,"['He, Muyi', 'Luo, Pan', 'Hong, Jie', 'Wang, Xiaofeng', 'Wu, Haimei', 'Zhang, Rongkai', 'Qu, Feng', 'Xiang, Ye', 'Xu, Wei']",ACS Omega,,,False
a49355dcd1dfe17df391674f41b4134a88e3c92e,PMC,"Lethal Encephalitis in Seals with Japanese Encephalitis Virus Infection, China, 2017",http://dx.doi.org/10.3201/eid2508.181663,PMC6649316,31310219,NO-CC CODE,"We isolated Japanese encephalitis virus (JEV) from brain samples of 2 seals with lethal encephalitis at Weihai Aquarium, Weihai, China, in 2017. We confirmed our findings by immunohistochemical staining and electron microscopy. Phylogenetic analysis showed this virus was genotype I. Our findings suggest that JEV might disseminate though infected zoo animals.",2019 Aug,"['Li, Xiangdong', 'Qiao, Mingming', 'Deng, Xiaoyu', 'Chen, Xi', 'Sun, Shengyong', 'Zhang, Qian', 'Zhang, Wenjie', 'Tan, Feifei', 'Sun, Zhe', 'Chen, Xizhao', 'Sun, Ming', 'Tian, Kegong']",Emerg Infect Dis,,,True
2b20afed6f91c23379ef9524c0eeb58cd616b0d5,PMC,"Natural Vertical Transmission of Zika Virus in Larval Aedes aegypti Populations, Morelos, Mexico",http://dx.doi.org/10.3201/eid2508.181533,PMC6649329,31310224,NO-CC CODE,"We characterized natural vertical transmission of Zika virus in pools of Aedes aegypti larvae hatched from eggs collected in Jojutla, Morelos, Mexico. Of the 151 pools analyzed, 17 tested positive for Zika virus RNA; infectious Zika virus was successfully isolated from 1 of the larvae pools (31N) in C6/36 cells. Real-time quantitative PCR and indirect immunofluorescence assays confirmed the identity of the isolate, named Zika virus isolate 31N; plaque assays in Vero cells demonstrated the isolate’s infectivity in a mammalian cell line. We obtained the complete genome of Zika virus isolate 31N by next-generation sequencing and identified 3 single-nucleotide variants specific to Zika virus isolate 31N using the meta-CATS tool. These results demonstrate the occurrence of natural vertical transmission of Zika virus in wild Ae. aegypti mosquitoes and suggest that this transmission mode could aid in the spread and maintenance of Zika virus in nature.",2019 Aug,"['Izquierdo-Suzán, Mónica', 'Zárate, Selene', 'Torres-Flores, Jesús', 'Correa-Morales, Fabián', 'González-Acosta, Cassandra', 'Sevilla-Reyes, Edgar E.', 'Lira, Rosalia', 'Alcaraz-Estrada, Sofía L.', 'Yocupicio-Monroy, Martha']",Emerg Infect Dis,,,True
0036e8891c93ae63611bde179ada1e03e8577dea,PMC,Stable Occupancy of the Crimean-Congo Hemorrhagic Fever Virus-Encoded Deubiquitinase Blocks Viral Infection,http://dx.doi.org/10.1128/mBio.01065-19,PMC6650548,31337717,NO-CC CODE,"Crimean-Congo hemorrhagic fever virus (CCHFV) infection can result in a severe hemorrhagic syndrome for which there are no antiviral interventions available to date. Certain RNA viruses, such as CCHFV, encode cysteine proteases of the ovarian tumor (OTU) family that antagonize interferon (IFN) production by deconjugating ubiquitin (Ub). The OTU of CCHFV, a negative-strand RNA virus, is dispensable for replication of the viral genome, despite being part of the large viral RNA polymerase. Here, we show that mutations that prevent binding of the OTU to cellular ubiquitin are required for the generation of recombinant CCHFV containing a mutated catalytic cysteine. Similarly, the high-affinity binding of a synthetic ubiquitin variant (UbV-CC4) to CCHFV OTU strongly inhibits viral growth. UbV-CC4 inhibits CCHFV infection even in the absence of intact IFN signaling, suggesting that its antiviral activity is not due to blocking the OTU’s immunosuppressive function. Instead, the prolonged occupancy of the OTU with UbV-CC4 directly targets viral replication by interfering with CCHFV RNA synthesis. Together, our data provide mechanistic details supporting the development of antivirals targeting viral OTUs.",2019 Jul 23,"['Scholte, Florine E. M.', 'Hua, Brian L.', 'Spengler, Jessica R.', 'Dzimianski, John V.', 'Coleman-McCray, JoAnn D.', 'Welch, Stephen R.', 'McMullan, Laura K.', 'Nichol, Stuart T.', 'Pegan, Scott D.', 'Spiropoulou, Christina F.', 'Bergeron, Éric']",mBio,,,True
8c0585738b7b2c5fd40e0fa0b18687b600ca5aef,PMC,First Complete Genome Sequence of Currently Circulating Infectious Bronchitis Virus Strain DMV/1639 of the GI-17 Lineage,http://dx.doi.org/10.1128/MRA.00840-19,PMC6706695,31439703,NO-CC CODE,"Avian infectious bronchitis virus is the causative agent of a highly contagious disease that results in severe economic losses to the poultry industry worldwide. Here, we report the first coding-complete genome sequence of strain DMV/1639 of the GI-17 lineage, isolated from broiler chickens in Georgia in 2019.",2019 Aug 22,"['Goraichuk, Iryna V.', 'Kulkarni, Arun B.', 'Williams-Coplin, Dawn', 'Suarez, David L.', 'Afonso, Claudio L.']",Microbiol Resour Announc,,,True
43d2d4072d40a3964ea330342b9222376d700531,PMC,Household Transmission of Human Adenovirus Type 55 in Case of Fatal Acute Respiratory Disease,http://dx.doi.org/10.3201/eid2509.181937,PMC6711205,31441750,NO-CC CODE,"We identified a case of fatal acute respiratory disease from household transmission of human adenovirus type 55 (HAdV-55) in Anhui Province, China. Computed tomography showed severe pneumonia. Comparative genomic analysis of HAdV-55 indicated the virus possibly originated in Shanxi Province, China. More attention should be paid to highly contagious HAdV-55.",2019 Sep,"['Jing, Shuping', 'Zhang, Jing', 'Cao, Mengchan', 'Liu, Minhong', 'Yan, Yuqian', 'Zhao, Shan', 'Cao, Na', 'Ou, Junxian', 'Ma, Kui', 'Cai, Xiangran', 'Wu, Jianguo', 'Mei, Ya-Fang', 'Zhang, Qiwei']",Emerg Infect Dis,,,True
c094157a1b1ddbbf67f13fda164c3609d4b26039,PMC,Household Transmission of Human Adenovirus Type 55 in Case of Fatal Acute Respiratory Disease,http://dx.doi.org/10.3201/eid2509.181937,PMC6711205,31441750,NO-CC CODE,"We identified a case of fatal acute respiratory disease from household transmission of human adenovirus type 55 (HAdV-55) in Anhui Province, China. Computed tomography showed severe pneumonia. Comparative genomic analysis of HAdV-55 indicated the virus possibly originated in Shanxi Province, China. More attention should be paid to highly contagious HAdV-55.",2019 Sep,"['Jing, Shuping', 'Zhang, Jing', 'Cao, Mengchan', 'Liu, Minhong', 'Yan, Yuqian', 'Zhao, Shan', 'Cao, Na', 'Ou, Junxian', 'Ma, Kui', 'Cai, Xiangran', 'Wu, Jianguo', 'Mei, Ya-Fang', 'Zhang, Qiwei']",Emerg Infect Dis,,,False
291ac6b6c787766b3628d2b7a3ee304c95e6baa0,PMC,Worldwide Reduction in MERS Cases and Deaths since 2016,http://dx.doi.org/10.3201/eid2509.190143,PMC6711233,31264567,NO-CC CODE,"Since 2012, Middle East respiratory syndrome (MERS) coronavirus has infected 2,442 persons worldwide. Case-based data analysis suggests that since 2016, as many as 1,465 cases and 293–520 deaths might have been averted. Efforts to reduce the global MERS threat are working, but countries must maintain vigilance to prevent further infections.",2019 Sep,"['Donnelly, Christl A.', 'Malik, Mamun R.', 'Elkholy, Amgad', 'Cauchemez, Simon', 'Van Kerkhove, Maria D.']",Emerg Infect Dis,,,True
5427108068edbf6065fc35c3c96476b41eba56f6,PMC,Worldwide Reduction in MERS Cases and Deaths since 2016,http://dx.doi.org/10.3201/eid2509.190143,PMC6711233,31264567,NO-CC CODE,"Since 2012, Middle East respiratory syndrome (MERS) coronavirus has infected 2,442 persons worldwide. Case-based data analysis suggests that since 2016, as many as 1,465 cases and 293–520 deaths might have been averted. Efforts to reduce the global MERS threat are working, but countries must maintain vigilance to prevent further infections.",2019 Sep,"['Donnelly, Christl A.', 'Malik, Mamun R.', 'Elkholy, Amgad', 'Cauchemez, Simon', 'Van Kerkhove, Maria D.']",Emerg Infect Dis,,,True
d785df22b7e40dd293869c502877d0af4e5b1821,PMC,The art of partnerships for vaccines()(),http://dx.doi.org/10.1016/j.vaccine.2019.07.088,PMC6739625,31447125,NO-CC CODE,"The Developing Countries Vaccine Manufacturers Network (DCVMN) convened vaccine manufacturing experts and leaders from local and global public health organizations for its 19th Annual General Meeting. Lectures and panel discussions centered on international cooperation for better access to vaccines, and partnerships in areas ranging from vaccine research and process development, to clinical studies, regulatory, supply chain and emergency preparedness and response. Global vaccine market trends and changes that will impact vaccine financing and procurement methods were discussed as well as capital sources, including funding, for the development of new or improved vaccines. DCVMN members presented their progress in developing novel Hexavalent, Meningitis, Pneumococcal Conjugate Vaccine, Shigella, Mumps, Rotavirus, Yellow Fever, Polio, Hepatitis E and Dengue vaccines, and a novel monoclonal antibody cocktail for post-bite prophylaxis against rabies infections. Access to and availability of vaccines is enhanced through sharing of best practices for vaccine quality control, reducing redundant testing and promoting development of harmonized common standards. Eligible stakeholders were encouraged to join the WHO-National Control Laboratory Network for Biologicals which serves as a platform for collaboration and technical exchange in this area. Increasing regulatory convergence at the regional and global levels through mechanisms such as joint dossier review and the WHO Collaborative Registration Procedure can help to accelerate vaccine access globally. Additionally, four proposals for streamlining procedures and alignment of dossiers were discussed. Successful partnerships between a broad range of stakeholders, including international organizations, manufacturers, academic research institutes and regulators have provided support for, and in some cases accelerated, vaccine innovation, clinical trials and registration, WHO prequalification, vaccine introduction and access. Strong partnerships, based on experience and trust, help leverage opportunities and are critically important to advancing the shared goal of providing quality vaccines for all people.",2019 Sep 20,"['Pagliusi, Sonia', 'Che, Yanchun', 'Dong, Shaozhong']",Vaccine,,,True
3f54832532dcb732e268f8a6d022d833cda56687,PMC,Long-Term Stability Monitoring of Printed Proteins on Paper-Based Membranes,http://dx.doi.org/10.1021/acsomega.9b02021,PMC6751693,31552358,NO-CC CODE,"[Image: see text] Monitoring of long-term stability of proteins on paper-based membranes is important as it is directly related to paper-based sensor fabrication. By using a simple piezo printhead inkjet printer, recombinant proteins and antibodies were printed on paper-based membranes to test their stability and sensitivity under varying lengths of storage and temperature conditions. Our data show that a printed IgG-HRP antibody on simple printing paper maintains >50% functionality up to ∼2 months under 4 and −20 °C storage. Antibodies printed on polyvinylidene difluoride (PVDF) and nitrocellulose showed 5.3 and 9.7% decreases, respectively, in initial signal intensities compared to printing paper. Prostate-specific membrane antigen and tumor necrosis factor alpha recombinant proteins printed on paper-based membranes can be detected by antibodies, and antibody signal intensities can be detected up to 28 days after storage at 4 and −20 °C when printed on PVDF membrane or printing paper. These data suggest that printed proteins on simple printing paper and PVDF membrane can maintain their functionality up to few months when stored at 4 °C or lower and can be potentially applied in paper-based sensor development.",2019 Aug 30,"['Koh, Byumseok', 'Kim, Kwang Rok']",ACS Omega,,,True
04733d9b91b1744e046dddef8b3253aa13a3c717,PMC,Sensitive and Specific Detection of Low-Level Antibody Responses in Mild Middle East Respiratory Syndrome Coronavirus Infections,http://dx.doi.org/10.3201/eid2510.190051,PMC6759241,31423970,NO-CC CODE,"Middle East respiratory syndrome coronavirus (MERS-CoV) infections in humans can cause asymptomatic to fatal lower respiratory lung disease. Despite posing a probable risk for virus transmission, asymptomatic to mild infections can go unnoticed; a lack of seroconversion among some PCR-confirmed cases has been reported. We found that a MERS-CoV spike S1 protein–based ELISA, routinely used in surveillance studies, showed low sensitivity in detecting infections among PCR-confirmed patients with mild clinical symptoms and cross-reactivity of human coronavirus OC43–positive serum samples. Using in-house S1 ELISA and protein microarray, we demonstrate that most PCR-confirmed MERS-CoV case-patients with mild infections seroconverted; nonetheless, some of these samples did not have detectable levels of virus-neutralizing antibodies. The use of a sensitive and specific serologic S1-based assay can be instrumental in the accurate estimation of MERS-CoV prevalence.",2019 Oct,"['Okba, Nisreen M.A.', 'Raj, V. Stalin', 'Widjaja, Ivy', 'GeurtsvanKessel, Corine H.', 'de Bruin, Erwin', 'Chandler, Felicity D.', 'Park, Wan Beom', 'Kim, Nam-Joong', 'Farag, Elmoubasher A.B.A.', 'Al-Hajri, Mohammed', 'Bosch, Berend-Jan', 'Oh, Myoung-don', 'Koopmans, Marion P.G.', 'Reusken, Chantal B.E.M.', 'Haagmans, Bart L.']",Emerg Infect Dis,,,True
2bee310d03a0fb03e14ba89d07407b7463fab209,PMC,Sensitive and Specific Detection of Low-Level Antibody Responses in Mild Middle East Respiratory Syndrome Coronavirus Infections,http://dx.doi.org/10.3201/eid2510.190051,PMC6759241,31423970,NO-CC CODE,"Middle East respiratory syndrome coronavirus (MERS-CoV) infections in humans can cause asymptomatic to fatal lower respiratory lung disease. Despite posing a probable risk for virus transmission, asymptomatic to mild infections can go unnoticed; a lack of seroconversion among some PCR-confirmed cases has been reported. We found that a MERS-CoV spike S1 protein–based ELISA, routinely used in surveillance studies, showed low sensitivity in detecting infections among PCR-confirmed patients with mild clinical symptoms and cross-reactivity of human coronavirus OC43–positive serum samples. Using in-house S1 ELISA and protein microarray, we demonstrate that most PCR-confirmed MERS-CoV case-patients with mild infections seroconverted; nonetheless, some of these samples did not have detectable levels of virus-neutralizing antibodies. The use of a sensitive and specific serologic S1-based assay can be instrumental in the accurate estimation of MERS-CoV prevalence.",2019 Oct,"['Okba, Nisreen M.A.', 'Raj, V. Stalin', 'Widjaja, Ivy', 'GeurtsvanKessel, Corine H.', 'de Bruin, Erwin', 'Chandler, Felicity D.', 'Park, Wan Beom', 'Kim, Nam-Joong', 'Farag, Elmoubasher A.B.A.', 'Al-Hajri, Mohammed', 'Bosch, Berend-Jan', 'Oh, Myoung-don', 'Koopmans, Marion P.G.', 'Reusken, Chantal B.E.M.', 'Haagmans, Bart L.']",Emerg Infect Dis,,,True
78cd9e16e1faec0b2b68a13b58d5be78408269b0,PMC,Comparison of Serologic Assays for Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.3201/eid2510.190497,PMC6759245,31423969,NO-CC CODE,"Middle East respiratory syndrome coronavirus (MERS-CoV) was detected in humans in 2012. Since then, sporadic outbreaks with primary transmission through dromedary camels to humans and outbreaks in healthcare settings have shown that MERS-CoV continues to pose a threat to human health. Several serologic assays for MERS-CoV have been developed globally. We describe a collaborative study to investigate the comparability of serologic assays for MERS-CoV and assess any benefit associated with the introduction of a standard reference reagent for MERS-CoV serology. Our study findings indicate that, when possible, laboratories should use a testing algorithm including >2 tests to ensure correct diagnosis of MERS-CoV. We also demonstrate that the use of a reference reagent greatly improves the agreement between assays, enabling more consistent and therefore more meaningful comparisons between results.",2019 Oct,"['Harvey, Ruth', 'Mattiuzzo, Giada', 'Hassall, Mark', 'Sieberg, Andrea', 'Müller, Marcel A.', 'Drosten, Christian', 'Rigsby, Peter', 'Oxenford, Christopher J.', None]",Emerg Infect Dis,,,True
a6e86c94af0d5da2d07a4d4047823ba8f829dad1,PMC,"Transmissibility of MERS-CoV Infection in Closed Setting, Riyadh, Saudi Arabia, 2015",http://dx.doi.org/10.3201/eid2510.190130,PMC6759265,31423971,NO-CC CODE,"To investigate a cluster of Middle East respiratory syndrome (MERS) cases in a women-only dormitory in Riyadh, Saudi Arabia, in October 2015, we collected epidemiologic information, nasopharyngeal/oropharyngeal swab samples, and blood samples from 828 residents during November 2015 and December 2015–January 2016. We found confirmed infection for 19 (8 by reverse transcription PCR and 11 by serologic testing). Infection attack rates varied (2.7%–32.3%) by dormitory building. No deaths occurred. Independent risk factors for infection were direct contact with a confirmed case-patient and sharing a room with a confirmed case-patient; a protective factor was having an air conditioner in the bedroom. For 9 women from whom a second serum sample was collected, antibodies remained detectable at titers >1:20 by pseudoparticle neutralization tests (n = 8) and 90% plaque-reduction neutralization tests (n = 2). In closed high-contact settings, MERS coronavirus was highly infectious and pathogenicity was relatively low.",2019 Oct,"['Van Kerkhove, Maria D.', 'Alaswad, Sadoof', 'Assiri, Abdullah', 'Perera, Ranawaka A.P.M.', 'Peiris, Malik', 'El Bushra, Hassan E.', 'BinSaeed, Abdulaziz A.']",Emerg Infect Dis,,,True
2a95ca7f6df1b967ca2fe08cedede51cda46f1b8,PMC,"Transmissibility of MERS-CoV Infection in Closed Setting, Riyadh, Saudi Arabia, 2015",http://dx.doi.org/10.3201/eid2510.190130,PMC6759265,31423971,NO-CC CODE,"To investigate a cluster of Middle East respiratory syndrome (MERS) cases in a women-only dormitory in Riyadh, Saudi Arabia, in October 2015, we collected epidemiologic information, nasopharyngeal/oropharyngeal swab samples, and blood samples from 828 residents during November 2015 and December 2015–January 2016. We found confirmed infection for 19 (8 by reverse transcription PCR and 11 by serologic testing). Infection attack rates varied (2.7%–32.3%) by dormitory building. No deaths occurred. Independent risk factors for infection were direct contact with a confirmed case-patient and sharing a room with a confirmed case-patient; a protective factor was having an air conditioner in the bedroom. For 9 women from whom a second serum sample was collected, antibodies remained detectable at titers >1:20 by pseudoparticle neutralization tests (n = 8) and 90% plaque-reduction neutralization tests (n = 2). In closed high-contact settings, MERS coronavirus was highly infectious and pathogenicity was relatively low.",2019 Oct,"['Van Kerkhove, Maria D.', 'Alaswad, Sadoof', 'Assiri, Abdullah', 'Perera, Ranawaka A.P.M.', 'Peiris, Malik', 'El Bushra, Hassan E.', 'BinSaeed, Abdulaziz A.']",Emerg Infect Dis,,,True
10d5a17a8cfc4407042a218f9d7acb53c41056e2,PMC,"STING, DCs and the link between innate and adaptive tumor immunity",http://dx.doi.org/10.1016/j.molimm.2017.12.001,PMC6768428,29273394,NO-CC CODE,"Cancer and the immune system are intimately related. Much of the bulk of tumors is comprised of stromal leukocytes with immune functions, which serve to both promote and inhibit tumor growth, invasion and metastasis. The T lymphocytes of the adaptive immune system are essential for tumor immunity, and these T cells are generated by cross-priming against tumor associated antigens. Dendritic cells (DCs) are essential in this process, serving as the cellular link between innate and adaptive immunity. As a prerequisite for priming of adaptive immune responses, DCs must take up tumor antigens, process them and present them in the context of the major histocompatibility complex (MHC). DCs also serve as sensors of innate activation signals from cancer that are necessary for their activation and effective priming of cancer specific T cells. Here we discuss the role of DCs in the sensing of cancer and in priming the adaptive response against tumors. Furthermore, we present the essential role of the Stimulator of Interferon Genes (STING) signaling pathway in producing type I interferons (IFNs) that are essential in this process.",2019 Jun 20,"['Vatner, Ralph E.', 'Janssen, Edith M.']",Mol Immunol,,,True
721ae2395d3848eebb9fea8ec837109d4cee111e,PMC,Precision mouse models with expanded tropism for human pathogens,http://dx.doi.org/10.1038/s41587-019-0225-9,PMC6776695,31451733,NO-CC CODE,"A major limitation of current humanized mouse models is that they primarily permit the analysis of human-specific pathogens that infect hematopoietic cells. However, most human pathogens target other cell types including epithelial, endothelial and mesenchymal cells. Here, we show that implantation of human lung tissue, that contains up to 40 cell types including non-hematopoietic cells, into immunodeficient mice (lung-only mice [LoM]) resulted in the development of a highly vascularized lung implant. We demonstrate that emerging and clinically relevant human pathogens such as Middle East respiratory syndrome coronavirus, Zika virus, respiratory syncytial virus, and cytomegalovirus replicate in vivo in these lung implants. When incorporated into bone marrow/liver/thymus (BLT) humanized mice (BLT-L mice), lung implants are repopulated with autologous human hematopoietic cells. We show robust antigen-specific humoral and T cell responses following cytomegalovirus infection that control virus replication. LoM and BLT-L mice dramatically increase the number of human pathogens that can be studied in vivo facilitating the in vivo testing of therapeutics.",2019 Oct 26,"['Wahl, Angela', 'De, Chandrav', 'Fernandez, Maria Abad', 'Lenarcic, Erik M.', 'Xu, Yinyan', 'Cockrell, Adam S.', 'Cleary, Rachel A.', 'Johnson, Claire E.', 'Schramm, Nathaniel J.', 'Rank, Laura M.', 'Newsome, Isabel G.', 'Vincent, Heather A.', 'Sanders, Wes', 'Aguilera-Sandoval, Christian R.', 'Boone, Allison', 'Hildebrand, William H.', 'Dayton, Paul A.', 'Baric, Ralph S.', 'Pickles, Raymond J.', 'Braunstein, Miriam', 'Moorman, Nathaniel J.', 'Goonetilleke, Nilu', 'Garcia, J. Victor']",Nat Biotechnol,,,True
62fe108d45109ea84383b7307f320bba73c56864,PMC,Precision mouse models with expanded tropism for human pathogens,http://dx.doi.org/10.1038/s41587-019-0225-9,PMC6776695,31451733,NO-CC CODE,"A major limitation of current humanized mouse models is that they primarily permit the analysis of human-specific pathogens that infect hematopoietic cells. However, most human pathogens target other cell types including epithelial, endothelial and mesenchymal cells. Here, we show that implantation of human lung tissue, that contains up to 40 cell types including non-hematopoietic cells, into immunodeficient mice (lung-only mice [LoM]) resulted in the development of a highly vascularized lung implant. We demonstrate that emerging and clinically relevant human pathogens such as Middle East respiratory syndrome coronavirus, Zika virus, respiratory syncytial virus, and cytomegalovirus replicate in vivo in these lung implants. When incorporated into bone marrow/liver/thymus (BLT) humanized mice (BLT-L mice), lung implants are repopulated with autologous human hematopoietic cells. We show robust antigen-specific humoral and T cell responses following cytomegalovirus infection that control virus replication. LoM and BLT-L mice dramatically increase the number of human pathogens that can be studied in vivo facilitating the in vivo testing of therapeutics.",2019 Oct 26,"['Wahl, Angela', 'De, Chandrav', 'Fernandez, Maria Abad', 'Lenarcic, Erik M.', 'Xu, Yinyan', 'Cockrell, Adam S.', 'Cleary, Rachel A.', 'Johnson, Claire E.', 'Schramm, Nathaniel J.', 'Rank, Laura M.', 'Newsome, Isabel G.', 'Vincent, Heather A.', 'Sanders, Wes', 'Aguilera-Sandoval, Christian R.', 'Boone, Allison', 'Hildebrand, William H.', 'Dayton, Paul A.', 'Baric, Ralph S.', 'Pickles, Raymond J.', 'Braunstein, Miriam', 'Moorman, Nathaniel J.', 'Goonetilleke, Nilu', 'Garcia, J. Victor']",Nat Biotechnol,,,False
327d5fb31ab8eb04ed90082b0ba448675c90208d,PMC,A single T cell epitope drives the neutralizing anti-drug antibody response to natalizumab in multiple sclerosis patients,http://dx.doi.org/10.1038/s41591-019-0568-2,PMC6795539,31501610,NO-CC CODE,"Natalizumab (NZM), a humanized monoclonal IgG4 antibody to α4 integrins, is used to treat patients with relapsing-remitting multiple sclerosis (MS)(1,2), but in about 6% of the cases persistent neutralizing anti-drug antibodies (ADAs) are induced leading to therapy discontinuation(3,4). To understand the basis of the ADA response and the mechanism of ADA-mediated neutralization, we performed an in-depth analysis of the B and T cell responses in two patients. By characterizing a large panel of NZM-specific monoclonal antibodies, we found that, in both patients, the response was polyclonal and targeted different epitopes of the NZM idiotype. The neutralizing activity was acquired through somatic mutations and correlated with a slow dissociation rate, a finding that was supported by structural data. Interestingly, in both patients, the analysis of the CD4(+) T cell response, combined with mass spectrometry-based peptidomics, revealed a single immunodominant T cell epitope spanning the FR2-CDR2 region of the NZM light chain. Moreover, a CDR2-modified version of NZM was not recognized by T cells, while retaining binding to α4 integrins. Collectively, our integrated analysis identifies the basis of T-B collaboration that leads to ADA-mediated therapeutic resistance and delineates an approach to design novel deimmunized antibodies for autoimmune disease and cancer treatment.",2019 Sep 9,"['Cassotta, Antonino', 'Mikol, Vincent', 'Bertrand, Thomas', 'Pouzieux, Stéphanie', 'Le Parc, Josiane', 'Ferrari, Paul', 'Dumas, Jacques', 'Auer, Michael', 'Deisenhammer, Florian', 'Gastaldi, Matteo', 'Franciotta, Diego', 'Silacci-Fregni, Chiara', 'Fernandez Rodriguez, Blanca', 'Giacchetto-Sasselli, Isabella', 'Foglierini, Mathilde', 'Jarrossay, David', 'Geiger, Roger', 'Sallusto, Federica', 'Lanzavecchia, Antonio', 'Piccoli, Luca']",Nat Med,,,True
2a274254f86c68ef4ae452143fc35e9cae52d77d,PMC,A single T cell epitope drives the neutralizing anti-drug antibody response to natalizumab in multiple sclerosis patients,http://dx.doi.org/10.1038/s41591-019-0568-2,PMC6795539,31501610,NO-CC CODE,"Natalizumab (NZM), a humanized monoclonal IgG4 antibody to α4 integrins, is used to treat patients with relapsing-remitting multiple sclerosis (MS)(1,2), but in about 6% of the cases persistent neutralizing anti-drug antibodies (ADAs) are induced leading to therapy discontinuation(3,4). To understand the basis of the ADA response and the mechanism of ADA-mediated neutralization, we performed an in-depth analysis of the B and T cell responses in two patients. By characterizing a large panel of NZM-specific monoclonal antibodies, we found that, in both patients, the response was polyclonal and targeted different epitopes of the NZM idiotype. The neutralizing activity was acquired through somatic mutations and correlated with a slow dissociation rate, a finding that was supported by structural data. Interestingly, in both patients, the analysis of the CD4(+) T cell response, combined with mass spectrometry-based peptidomics, revealed a single immunodominant T cell epitope spanning the FR2-CDR2 region of the NZM light chain. Moreover, a CDR2-modified version of NZM was not recognized by T cells, while retaining binding to α4 integrins. Collectively, our integrated analysis identifies the basis of T-B collaboration that leads to ADA-mediated therapeutic resistance and delineates an approach to design novel deimmunized antibodies for autoimmune disease and cancer treatment.",2019 Sep 9,"['Cassotta, Antonino', 'Mikol, Vincent', 'Bertrand, Thomas', 'Pouzieux, Stéphanie', 'Le Parc, Josiane', 'Ferrari, Paul', 'Dumas, Jacques', 'Auer, Michael', 'Deisenhammer, Florian', 'Gastaldi, Matteo', 'Franciotta, Diego', 'Silacci-Fregni, Chiara', 'Fernandez Rodriguez, Blanca', 'Giacchetto-Sasselli, Isabella', 'Foglierini, Mathilde', 'Jarrossay, David', 'Geiger, Roger', 'Sallusto, Federica', 'Lanzavecchia, Antonio', 'Piccoli, Luca']",Nat Med,,,False
6450de33d673aaaeef75fc898f74ca3e9caec89d,PMC,"Practical Healthcare Epidemiology, 4th Edition",http://dx.doi.org/10.3201/eid2511.190464,PMC6810204,,NO-CC CODE,,2019 Nov,"Lifshitz, Edward",Emerg Infect Dis,,,True
a0839bf8f94d79c1253bf89f170c22f9342fc095,PMC,"Middle East Respiratory Syndrome Coronavirus, Saudi Arabia, 2017–2018",http://dx.doi.org/10.3201/eid2511.190726,PMC6810214,31430248,NO-CC CODE,"We characterized exposures and demographics of Middle East respiratory syndrome coronavirus cases reported to the Saudi Arabia Ministry of Health during July 1–October 31, 2017, and June 1–September 16, 2018. Molecular characterization of available specimens showed that circulating viruses during these periods continued to cluster within lineage 5.",2019 Nov,"['Hakawi, Ahmed', 'Rose, Erica Billig', 'Biggs, Holly M.', 'Lu, Xiaoyan', 'Mohammed, Mutaz', 'Abdalla, Osman', 'Abedi, Glen R.', 'Alsharef, Ali A.', 'Alamri, Aref Ali', 'Bereagesh, Samar Ahmad', 'Al Dosari, Kamel M.', 'Ashehri, Saad Abdullah', 'Fakhouri, Waad Ghassan', 'Alzaid, Saleh Zaid', 'Lindstrom, Stephen', 'Gerber, Susan I.', 'Asiri, Abdullah', 'Jokhdar, Hani', 'Watson, John T.']",Emerg Infect Dis,,,True
d8716057edc20cdcb232b1ce062ff2804bfd041d,PMC,Evaluation of Ultra-Microscopic Changes and Proliferation of Apoptotic Glioblastoma Multiforme Cells Induced by Velogenic Strain of Newcastle Disease Virus AF2240,http://dx.doi.org/10.31557/APJCP.2019.20.3.757,PMC6825790,30909682,NO-CC CODE,"AIM: Newcastle disease virus (NDV) is a member of genus Avulavirus within the family Paramyxoviridae. Interest of using NDV as an anticancer agent has arisen from its ability to kill tumor cells with limited toxicity to normal cells. METHODS: In this investigation, the proliferation of brain tumor cell line, glioblastoma multiform (DBTRG.05MG) induced by NDV strain AF2240 was evaluated in-vitro, by using MTT proliferation assay. Furthermore, Cytological observations were studied using fluorescence microscopy and transmission electron microscopy, DNA laddering in agarose gel electrophoresis assay used to detect the mode of cell death and analysis of the cellular DNA content by flowcytometery. RESULTS: MTT proliferation assay, Cytological observations using fluorescence microscopy and transmission electron microscopy show the anti-proliferation effect and apoptogenic features of NDV on DBTRG.05MG. Furthermore, analysis of the cellular DNA content showed that there was a loss of treated cells in all cell cycle phases (G1, S and G2/M) accompanied with increasing in sub-G1 region (apoptosis peak). CONCLUSION: It could be concluded that NDV strain AF2240 is a potent antitumor agent that induce apoptosis and its cytotoxicity increasing while increasing of time and virus titer.",2019,"['Ali-Saeed, Rola', 'Alabsi, Aied M', 'Ideris, Aini', 'Omar, Abdul Rahman', 'Yusoff, Khatijah', 'Ali, Abdul Manaf']",Asian Pac J Cancer Prev,,,True
d3a675bfc74c8ebef84c248dca0b8cc05f5b3ce1,PMC,A method of processing nasopharyngeal swabs to enable multiple testing,http://dx.doi.org/10.1038/s41390-019-0498-1,PMC6851467,31288247,NO-CC CODE,"OBJECTIVE: To develop a method to perform multiple tests on single nasopharyngeal (NP) swab. STUDY DESIGN: We collected a NP swab on children aged 2–12 years with acute sinusitis and processed it for bacterial culture, viruses, cytokine expression, and 16S ribosomal RNA gene sequencing analysis. During the course of the study, we expand the scope of evaluation to include RNA sequencing, which we accomplished by cutting the tip of the swab. RESULTS: Of the 174 children enrolled, 126 (72.4%) had a positive bacterial culture and 121(69.5%) tested positive for a virus. Cytokine measurement, as judged by the adequate levels of a housekeeping enzyme (GAPDH), appeared successful. From the samples used for 16S ribosomal sequencing we recovered, on average, 16,000 sequences per sample, accounting for a total of 2,646 operational taxonomic units across all samples sequenced. Samples used for RNA sequencing had a mean RNA Integrity number of 6.0. Cutting the tip of the swab did not affect the recovery yield for viruses or bacteria, nor did it affect species richness in microbiome analysis. CONCLUSION: We describe a minimally invasive sample collection protocol that allows for multiple diagnostic and research investigations in young children.",2019 Nov 9,"['Lopez, Santiago M.C.', 'Martin, Judith M.', 'Johnson, Monika', 'Kurs-Lasky, Marcia', 'Horne, William T.', 'Marshall, Christopher W', 'Cooper, Vaughn S.', 'Williams, John V.', 'Shaikh, Nader']",Pediatr Res,,,True
f267747d7aa533058e77f5290cbd605547a23579,PMC,A method of processing nasopharyngeal swabs to enable multiple testing,http://dx.doi.org/10.1038/s41390-019-0498-1,PMC6851467,31288247,NO-CC CODE,"OBJECTIVE: To develop a method to perform multiple tests on single nasopharyngeal (NP) swab. STUDY DESIGN: We collected a NP swab on children aged 2–12 years with acute sinusitis and processed it for bacterial culture, viruses, cytokine expression, and 16S ribosomal RNA gene sequencing analysis. During the course of the study, we expand the scope of evaluation to include RNA sequencing, which we accomplished by cutting the tip of the swab. RESULTS: Of the 174 children enrolled, 126 (72.4%) had a positive bacterial culture and 121(69.5%) tested positive for a virus. Cytokine measurement, as judged by the adequate levels of a housekeeping enzyme (GAPDH), appeared successful. From the samples used for 16S ribosomal sequencing we recovered, on average, 16,000 sequences per sample, accounting for a total of 2,646 operational taxonomic units across all samples sequenced. Samples used for RNA sequencing had a mean RNA Integrity number of 6.0. Cutting the tip of the swab did not affect the recovery yield for viruses or bacteria, nor did it affect species richness in microbiome analysis. CONCLUSION: We describe a minimally invasive sample collection protocol that allows for multiple diagnostic and research investigations in young children.",2019 Nov 9,"['Lopez, Santiago M.C.', 'Martin, Judith M.', 'Johnson, Monika', 'Kurs-Lasky, Marcia', 'Horne, William T.', 'Marshall, Christopher W', 'Cooper, Vaughn S.', 'Williams, John V.', 'Shaikh, Nader']",Pediatr Res,,,False
cc44d4c57c66a9c62c60fa0e3908462e812987c1,PMC,Optimal fluid management in sepsis,http://dx.doi.org/10.5339/qmj.2019.qccc.40,PMC6851923,,NO-CC CODE,"Sepsis clinically manifests as life-threatening organ dysfunction due to a dysregulated host response to infection.(1) Optimal fluid resuscitation is relevant for all sepsis patients, and perhaps it is most important for those with septic shock. Septic shock is defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greatest risk of mortality, and septic shock is clinically identified as sepsis patients with serum lactate level >2 mmol/L and who require vasopressor infusion to maintain a mean arterial pressure ≥  65 mm Hg in the absence of hypovolemia. Sepsis is among the most common conditions in the intensive care unit (ICU), accounting for up to half of all hospital deaths and being the third leading cause of death overall in the United States.(2) Sepsis and septic shock are medical emergencies for which treatment and resuscitation should begin immediately. The goals of fluid resuscitation for these patients are: a) to rapidly replace intravascular volume and restore tissue perfusion, and b) to minimize organ dysfunction through timely interventions that either halt or reverse the physiologic derangements. If hypoperfusion is present, at least 30 mL/kg of IV crystalloid fluid should be given rapidly, and additional fluids should be guided by frequent reassessment of hemodynamic status, preferably using dynamic indices to indicate the likelihood of a beneficial response to fluid administration. Fluid administration should be targeted to achieve a MAP of at least 65 mm Hg, and to normalize lactate in patients with elevated lactate due to hypoperfusion.(3) Balanced crystalloids are the fluid of first choice for sepsis resuscitation based on ready availability and taking medication costs into account. Use of 0.9% saline compared to a balanced crystalloid, such as lactated Ringer's or PlasmaLyte, produces more kidney dysfunction and with a greater risk of dying.(4) The individual side effect profiles may best differentiate the natural and synthetic colloids. Albumin may be considered for administration to sepsis patients with refractory shock or who have received substantial amounts of crystalloid fluids, but should not be administered to patients with severe traumatic brain injury.(5) Hydroxyethyl starch (HES) products should not be administered to patients with sepsis because of increased risk of acute kidney injury and death. Gelatin solutions are not recommended in sepsis. Norepinephrine is the vasopressor of first choice for patients with septic shock, and should be administered to achieve a mean arterial pressure of at least 65 mm Hg after excluding hypovolemia as a cause for hypotension. The selection of a second line vasopressor, such as vasopressin, dopamine, phenylephrine, epinephrine or angiotensin-2, depends on patient factors such as underlying cardiac dysfunction, presence of arrhythmias, and current response to vasoconstrictor or inotropic agents. Dopamine should not be used for renal perfusion or protection and it should be avoided in patients with tachyarrhythmias.",2019 Nov 7,"Martin, Greg S.",Qatar Med J,,,True
bdd29bc2544c4db266bcec6b7b404e5c360ca35f,PMC,Infectious Disease Management and Control with Povidone Iodine,http://dx.doi.org/10.1007/s40121-019-00260-x,PMC6856232,31414403,NO-CC CODE,"With reports of vancomycin-resistant enterococci recently emerging in hospital settings, renewed focus is turning to the importance of multifaceted infection prevention efforts. Careful compliance with established hygiene practices by healthcare workers together with effective antiseptic options is essential for the protection of patients from infectious agents. For over 60 years, povidone iodine (PVP-I) formulations have been shown to limit the impact and spread of infectious diseases with potent antiviral, antibacterial and antifungal effects. In addition to a lack of reported resistance, the benefits of PVP-I include an excellent safety profile and a broad spectrum of effect due to its multimodal action. Studies have shown that hand washing with PVP-I-based antiseptics is effective for the decontamination of skin, while PVP-I mouthwashes and gargles significantly reduce viral load in the oral cavity and the oropharynx. The importance of PVP-I has been emphasised by its inclusion in the World Health Organization’s list of essential medicines, and high potency for virucidal activity has been observed against viruses of significant global concern, including hepatitis A and influenza, as well as the Middle-East Respiratory Syndrome and Sudden Acute Respiratory Syndrome coronaviruses. Together with its diverse applications in antimicrobial control, broad accessibility across the globe, and outstanding safety and tolerability profile, PVP-I offers an affordable, potent, and widely available antiseptic option. Funding Mundipharma Singapore Holding Pte Limited.",2019 Dec 14,"Eggers, Maren",Infect Dis Ther,,,True
6581fa08f3fffd579f9a627ea9ba7596a5dcaee6,PMC,The Art of Intertwining Life and Work,http://dx.doi.org/10.3201/eid2009.AC2009,PMC6860145,25295334,NO-CC CODE,,2014 Sep,"['Breedlove, Byron', 'Chuengsatiansup, Komatra']",Emerg Infect Dis,,,True
7d301234c3251abee951f0877e8d3a3b1fca6221,PMC,Examining the relationship between household air pollution and infant microbial nasal carriage in a Ghanaian cohort,http://dx.doi.org/10.1016/j.envint.2019.105150,PMC6868532,31518936,NO-CC CODE,"BACKGROUND: Pneumonia, a leading cause of childhood mortality, is associated with household air pollution (HAP) exposure. Mechanisms between HAP and pneumonia are poorly understood, but studies suggest that HAP may increase the likelihood of bacterial, instead of viral, pneumonia. We assessed the relationship between HAP and infant microbial nasal carriage among 260 infants participating in the Ghana Randomized Air Pollution and Health Study (GRAPHS). METHODS: Data are from GRAPHS, a cluster-randomized controlled trial of cookstove interventions (improved biomass or LPG) versus the 3-stone (baseline) cookstove. Infants were surveyed for pneumonia during the first year of life and had routine personal exposure assessments. Nasopharyngeal swabs collected from pneumonia cases (n = 130) and healthy controls (n = 130) were analyzed for presence of 22 common respiratory microbes by MassTag polymerase chain reaction. Data analyses included intention-to-treat (ITT) comparisons of microbial species presence by study arm, and exposure-response relationships. RESULTS: In ITT analyses, 3-stone arm participants had a higher mean number of microbial species than the LPG (LPG: 2.71, 3-stone: 3.34, p < 0.0001, n = 260). This difference was driven by increased bacterial (p < 0.0001) rather than viral species presence (non-significant). Results were pronounced in pneumonia cases and attenuated in healthy controls. Higher prevalence bacterial species were Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Exposure-response relationships did not yield significant associations between measured CO and nasal microbial carriage. CONCLUSIONS: Our intention-to-treat findings are consistent with a link between HAP and bacterial nasal carriage. No relationships were found for viral carriage. Given the null results in exposure-response analysis, it is likely that a pollutant besides CO is driving these differences.",2019 Dec 10,"['Carrión, Daniel', 'Kaali, Seyram', 'Kinney, Patrick L.', 'Owusu-Agyei, Seth', 'Chillrud, Steven', 'Yawson, Abena K.', 'Quinn, Ashlinn', 'Wylie, Blair', 'Ae-Ngibise, Kenneth', 'Lee, Alison G.', 'Tokarz, Rafal', 'Iddrisu, Luisa', 'Jack, Darby W.', 'Asante, Kwaku Poku']",Environ Int,,,True
041d8935d19cbab390d587a9835544b09de053e5,PMC,Examining the relationship between household air pollution and infant microbial nasal carriage in a Ghanaian cohort,http://dx.doi.org/10.1016/j.envint.2019.105150,PMC6868532,31518936,NO-CC CODE,"BACKGROUND: Pneumonia, a leading cause of childhood mortality, is associated with household air pollution (HAP) exposure. Mechanisms between HAP and pneumonia are poorly understood, but studies suggest that HAP may increase the likelihood of bacterial, instead of viral, pneumonia. We assessed the relationship between HAP and infant microbial nasal carriage among 260 infants participating in the Ghana Randomized Air Pollution and Health Study (GRAPHS). METHODS: Data are from GRAPHS, a cluster-randomized controlled trial of cookstove interventions (improved biomass or LPG) versus the 3-stone (baseline) cookstove. Infants were surveyed for pneumonia during the first year of life and had routine personal exposure assessments. Nasopharyngeal swabs collected from pneumonia cases (n = 130) and healthy controls (n = 130) were analyzed for presence of 22 common respiratory microbes by MassTag polymerase chain reaction. Data analyses included intention-to-treat (ITT) comparisons of microbial species presence by study arm, and exposure-response relationships. RESULTS: In ITT analyses, 3-stone arm participants had a higher mean number of microbial species than the LPG (LPG: 2.71, 3-stone: 3.34, p < 0.0001, n = 260). This difference was driven by increased bacterial (p < 0.0001) rather than viral species presence (non-significant). Results were pronounced in pneumonia cases and attenuated in healthy controls. Higher prevalence bacterial species were Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Exposure-response relationships did not yield significant associations between measured CO and nasal microbial carriage. CONCLUSIONS: Our intention-to-treat findings are consistent with a link between HAP and bacterial nasal carriage. No relationships were found for viral carriage. Given the null results in exposure-response analysis, it is likely that a pollutant besides CO is driving these differences.",2019 Dec 10,"['Carrión, Daniel', 'Kaali, Seyram', 'Kinney, Patrick L.', 'Owusu-Agyei, Seth', 'Chillrud, Steven', 'Yawson, Abena K.', 'Quinn, Ashlinn', 'Wylie, Blair', 'Ae-Ngibise, Kenneth', 'Lee, Alison G.', 'Tokarz, Rafal', 'Iddrisu, Luisa', 'Jack, Darby W.', 'Asante, Kwaku Poku']",Environ Int,,,False
6f323c90b04d5ff3fbcfdd8ff38c805d7c13fb7f,PMC,"Middle East Respiratory Syndrome Coronavirus Seropositivity in Camel Handlers and Their Families, Pakistan",http://dx.doi.org/10.3201/eid2512.191169,PMC6874235,31742530,NO-CC CODE,"A high percentage of camel handlers in Saudi Arabia are seropositive for Middle East respiratory syndrome coronavirus. We found that 12/100 camel handlers and their family members in Pakistan, a country with extensive camel MERS-CoV infection, were seropositive, indicating that MERS-CoV infection of these populations extends beyond the Arabian Peninsula.",2019 Dec,"['Zheng, Jian', 'Hassan, Sohail', 'Alagaili, Abdulaziz N.', 'Alshukairi, Abeer N.', 'Amor, Nabil M.S.', 'Mukhtar, Nadia', 'Nazeer, Iqra Maleeha', 'Tahir, Zarfishan', 'Akhter, Nadeem', 'Perlman, Stanley', 'Yaqub, Tahir']",Emerg Infect Dis,,,True
0c367effaaef055c22eea78503485732adb70cb1,PMC,"Middle East Respiratory Syndrome Coronavirus Seropositivity in Camel Handlers and Their Families, Pakistan",http://dx.doi.org/10.3201/eid2512.191169,PMC6874235,31742530,NO-CC CODE,"A high percentage of camel handlers in Saudi Arabia are seropositive for Middle East respiratory syndrome coronavirus. We found that 12/100 camel handlers and their family members in Pakistan, a country with extensive camel MERS-CoV infection, were seropositive, indicating that MERS-CoV infection of these populations extends beyond the Arabian Peninsula.",2019 Dec,"['Zheng, Jian', 'Hassan, Sohail', 'Alagaili, Abdulaziz N.', 'Alshukairi, Abeer N.', 'Amor, Nabil M.S.', 'Mukhtar, Nadia', 'Nazeer, Iqra Maleeha', 'Tahir, Zarfishan', 'Akhter, Nadeem', 'Perlman, Stanley', 'Yaqub, Tahir']",Emerg Infect Dis,,,False
d84f1c9036052ca0d9f8216cac4c5118ad8cea19,PMC,Half-Life of African Swine Fever Virus in Shipped Feed,http://dx.doi.org/10.3201/eid2512.191002,PMC6874236,31524583,NO-CC CODE,"African swine fever virus is transmissible through animal consumption of contaminated feed. To determine virus survival during transoceanic shipping, we calculated the half-life of the virus in 9 feed ingredients exposed to 30-day shipment conditions. Half-lives ranged from 9.6 to 14.2 days, indicating that the feed matrix environment promotes virus stability.",2019 Dec,"['Stoian, Ana M.M.', 'Zimmerman, Jeff', 'Ji, Ju', 'Hefley, Trevor J.', 'Dee, Scott', 'Diel, Diego G.', 'Rowland, Raymond R.R.', 'Niederwerder, Megan C.']",Emerg Infect Dis,,,True
ba31adca4b7af49cd5e209dd5ad53a1ca30723c6,PMC,"MERS-CoV in Camels but Not Camel Handlers, Sudan, 2015 and 2017",http://dx.doi.org/10.3201/eid2512.190882,PMC6874263,31742534,NO-CC CODE,"We tested samples collected from camels, camel workers, and other animals in Sudan and Qatar in 2015 and 2017 for evidence of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. MERS-CoV antibodies were abundant in Sudan camels, but we found no evidence of MERS-CoV infection in camel workers, other livestock, or bats.",2019 Dec,"['Farag, Elmoubasher', 'Sikkema, Reina S.', 'Mohamedani, Ahmed A.', 'de Bruin, Erwin', 'Munnink, Bas B. Oude', 'Chandler, Felicity', 'Kohl, Robert', 'van der Linden, Anne', 'Okba, Nisreen M.A.', 'Haagmans, Bart L.', 'van den Brand, Judith M.A.', 'Elhaj, Asia Mohamed', 'Abakar, Adam D.', 'Nour, Bakri Y.M.', 'Mohamed, Ahmed M.', 'Alwaseela, Bader Eldeen', 'Ahmed, Husna', 'Alhajri, Mohd Mohd', 'Koopmans, Marion', 'Reusken, Chantal', 'Elrahman, Samira Hamid Abd']",Emerg Infect Dis,,,True
9fbbae703d150466db0f5312aa28bb4f449a1f9d,PMC,Applying a Linear Amplification Strategy to Recombinase Polymerase Amplification for Uniform DNA Library Amplification,http://dx.doi.org/10.1021/acsomega.9b02886,PMC6882106,31788628,NO-CC CODE,"[Image: see text] Recombinase polymerase amplification (RPA) is an isothermal DNA amplification method with broad applications as a point-of-care test and in molecular biology techniques. Currently, most of the applications are focused on target-specific amplification. Because RPA has the advantage of amplifying DNA under isothermal conditions, we utilized RPA as a DNA library amplification tool. In this study, we used a sheared genomic DNA library and an oligonucleotide (oligo) library for the comparison of polymerase chain reaction and RPA. For the sheared DNA library, we observed biased amplification after RPA was conducted. Thus, to amplify the size-variable DNA library uniformly, we introduced a linear amplification strategy with RPA and successfully improved the uniformity. On the other hand, using the same-sized oligo library, we confirmed that RPA amplified this library uniformly without modification of the protocol. These results demonstrate that RPA can be applied not only to amplify a specific target as previously demonstrated but also to amplify a complex DNA library composed of a large number of different DNA molecules.",2019 Nov 12,"['Lee, Jeewon', 'Heo, Sunghoon', 'Bang, Duhee']",ACS Omega,,,True
a3a52497caf1eea460b96a1e5dc9fb9898878045,PMC,Applying a Linear Amplification Strategy to Recombinase Polymerase Amplification for Uniform DNA Library Amplification,http://dx.doi.org/10.1021/acsomega.9b02886,PMC6882106,31788628,NO-CC CODE,"[Image: see text] Recombinase polymerase amplification (RPA) is an isothermal DNA amplification method with broad applications as a point-of-care test and in molecular biology techniques. Currently, most of the applications are focused on target-specific amplification. Because RPA has the advantage of amplifying DNA under isothermal conditions, we utilized RPA as a DNA library amplification tool. In this study, we used a sheared genomic DNA library and an oligonucleotide (oligo) library for the comparison of polymerase chain reaction and RPA. For the sheared DNA library, we observed biased amplification after RPA was conducted. Thus, to amplify the size-variable DNA library uniformly, we introduced a linear amplification strategy with RPA and successfully improved the uniformity. On the other hand, using the same-sized oligo library, we confirmed that RPA amplified this library uniformly without modification of the protocol. These results demonstrate that RPA can be applied not only to amplify a specific target as previously demonstrated but also to amplify a complex DNA library composed of a large number of different DNA molecules.",2019 Nov 12,"['Lee, Jeewon', 'Heo, Sunghoon', 'Bang, Duhee']",ACS Omega,,,False
e1dc3ea3a7ad4303e6e57417de0daee78e31d5bb,PMC,Evaluation of the Antiviral Potential of Halogenated Dihydrorugosaflavonoids and Molecular Modeling with nsP3 Protein of Chikungunya Virus (CHIKV),http://dx.doi.org/10.1021/acsomega.9b02900,PMC6893968,31815237,NO-CC CODE,"[Image: see text] Antiviral therapy is crucial for the circumvention of viral epidemics. The unavailability of a specific antiviral drug against the chikungunya virus (CHIKV) disease has created an alarming situation to identify or develop potent chemical molecules for remedial management of CHIKV. In the present investigation, in silico studies of dihydrorugosaflavonoid derivatives (5a–f) with non-structural protein-3 (nsP3) were carried out. nsP3 replication protein has recently been considered as a possible antiviral target in which crucial inhibitors fit into the adenosine-binding pocket of the macrodomain. The 4′-halogenated dihydrorugosaflavonoids displayed intrinsic binding with the nsp3 macrodomain (PDB ID: 3GPO) of CHIKV. Compounds 5c and 5d showed docking scores of −7.54 and −6.86 kcal mol(–1), respectively. Various in vitro assays were performed to confirm their (5a–f) antiviral potential against CHIKV. The non-cytotoxic dose was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and was found to be <100 μM. The compounds 5c and 5d showed their inhibitory potential for CHIKV, which was determined through cytopathic effect assay and plaque reduction assay, which show inhibition up to 95 and 92% for 70 μM concentration of the compounds, respectively. The quantitative real-time polymerase chain reaction assay result confirmed the ability of 5c and 5d to reduce the viral RNA level at 70 μM concentration of compounds to nearly 95 and 93% concentration, respectively, in cells with CHIKV infection. Further, the CHIKV-inhibitory capacity of these compounds was corroborated by execution of immunofluorescence assay. The executed work will be meaningful for the future research of studied dihydrorugosaflavonoids against prime antiviral entrants, leading to remedial management to preclude CHIKV infection.",2019 Nov 18,"['Puranik, Ninad\nV.', 'Rani, Ruchi', 'Singh, Vedita Anand', 'Tomar, Shailly', 'Puntambekar, Hemalata M.', 'Srivastava, Pratibha']",ACS Omega,,,True
d8086566c63a32aa57e8fe541d3877879568a1fa,PMC,Evaluation of the Antiviral Potential of Halogenated Dihydrorugosaflavonoids and Molecular Modeling with nsP3 Protein of Chikungunya Virus (CHIKV),http://dx.doi.org/10.1021/acsomega.9b02900,PMC6893968,31815237,NO-CC CODE,"[Image: see text] Antiviral therapy is crucial for the circumvention of viral epidemics. The unavailability of a specific antiviral drug against the chikungunya virus (CHIKV) disease has created an alarming situation to identify or develop potent chemical molecules for remedial management of CHIKV. In the present investigation, in silico studies of dihydrorugosaflavonoid derivatives (5a–f) with non-structural protein-3 (nsP3) were carried out. nsP3 replication protein has recently been considered as a possible antiviral target in which crucial inhibitors fit into the adenosine-binding pocket of the macrodomain. The 4′-halogenated dihydrorugosaflavonoids displayed intrinsic binding with the nsp3 macrodomain (PDB ID: 3GPO) of CHIKV. Compounds 5c and 5d showed docking scores of −7.54 and −6.86 kcal mol(–1), respectively. Various in vitro assays were performed to confirm their (5a–f) antiviral potential against CHIKV. The non-cytotoxic dose was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and was found to be <100 μM. The compounds 5c and 5d showed their inhibitory potential for CHIKV, which was determined through cytopathic effect assay and plaque reduction assay, which show inhibition up to 95 and 92% for 70 μM concentration of the compounds, respectively. The quantitative real-time polymerase chain reaction assay result confirmed the ability of 5c and 5d to reduce the viral RNA level at 70 μM concentration of compounds to nearly 95 and 93% concentration, respectively, in cells with CHIKV infection. Further, the CHIKV-inhibitory capacity of these compounds was corroborated by execution of immunofluorescence assay. The executed work will be meaningful for the future research of studied dihydrorugosaflavonoids against prime antiviral entrants, leading to remedial management to preclude CHIKV infection.",2019 Nov 18,"['Puranik, Ninad\nV.', 'Rani, Ruchi', 'Singh, Vedita Anand', 'Tomar, Shailly', 'Puntambekar, Hemalata M.', 'Srivastava, Pratibha']",ACS Omega,,,False
3dfce0f1586b904eb6afcda376c0295d3de6c295,PMC,"Diabetes Mellitus, Hypertension, and Death among 32 Patients with MERS-CoV Infection, Saudi Arabia",http://dx.doi.org/10.3201/eid2601.190952,PMC6924889,31855530,NO-CC CODE,"Diabetes mellitus and hypertension are recognized risk factors for severe clinical outcomes, including death, associated with Middle East respiratory syndrome coronavirus infection. Among 32 virus-infected patients in Saudi Arabia, severity of illness and frequency of death corresponded closely with presence of multiple and more severe underlying conditions.",2020 Jan,"['Alanazi, Khalid H.', 'Abedi, Glen R.', 'Midgley, Claire M.', 'Alkhamis, Abdulrahim', 'Alsaqer, Taghreed', 'Almoaddi, Abdullah', 'Algwizani, Abdullah', 'Ghazal, Sameeh S.', 'Assiri, Abdullah M.', 'Jokhdar, Hani', 'Gerber, Susan I.', 'Alabdely, Hail', 'Watson, John T.']",Emerg Infect Dis,,,True
46923a6d3d7d0b7f7252c7161fad5126636bcb7e,PMC,"Diabetes Mellitus, Hypertension, and Death among 32 Patients with MERS-CoV Infection, Saudi Arabia",http://dx.doi.org/10.3201/eid2601.190952,PMC6924889,31855530,NO-CC CODE,"Diabetes mellitus and hypertension are recognized risk factors for severe clinical outcomes, including death, associated with Middle East respiratory syndrome coronavirus infection. Among 32 virus-infected patients in Saudi Arabia, severity of illness and frequency of death corresponded closely with presence of multiple and more severe underlying conditions.",2020 Jan,"['Alanazi, Khalid H.', 'Abedi, Glen R.', 'Midgley, Claire M.', 'Alkhamis, Abdulrahim', 'Alsaqer, Taghreed', 'Almoaddi, Abdullah', 'Algwizani, Abdullah', 'Ghazal, Sameeh S.', 'Assiri, Abdullah M.', 'Jokhdar, Hani', 'Gerber, Susan I.', 'Alabdely, Hail', 'Watson, John T.']",Emerg Infect Dis,,,False
7d102f0d9bd25cf5ac225ae0312a2f6c66f4b9a5,PMC,"Bovine Kobuvirus in Calves with Diarrhea, United States",http://dx.doi.org/10.3201/eid2601.191227,PMC6924891,31855534,NO-CC CODE,We detected bovine kobuvirus (BKV) in calves with diarrhea in the United States. The strain identified is related genetically to BKVs detected in other countries. Histopathologic findings also confirmed viral infection in 2 BKV cases. Our data show BKV is a potential causative agent for diarrhea in calves.,2020 Jan,"['Wang, Leyi', 'Fredrickson, Richard', 'Duncan, Michelle', 'Samuelson, Jonathan', 'Hsiao, Shih-Hsuan']",Emerg Infect Dis,,,True
eb4d18fcf88cd102e67340cf8d3503f7da99bc8e,PMC,"Bovine Kobuvirus in Calves with Diarrhea, United States",http://dx.doi.org/10.3201/eid2601.191227,PMC6924891,31855534,NO-CC CODE,We detected bovine kobuvirus (BKV) in calves with diarrhea in the United States. The strain identified is related genetically to BKVs detected in other countries. Histopathologic findings also confirmed viral infection in 2 BKV cases. Our data show BKV is a potential causative agent for diarrhea in calves.,2020 Jan,"['Wang, Leyi', 'Fredrickson, Richard', 'Duncan, Michelle', 'Samuelson, Jonathan', 'Hsiao, Shih-Hsuan']",Emerg Infect Dis,,,False
05326cc45fa2898c5850df85d30dad3d2c82acef,PMC,"Influenza A Virus Infections in Dromedary Camels, Nigeria and Ethiopia, 2015–2017",http://dx.doi.org/10.3201/eid2601.191165,PMC6924894,31855544,NO-CC CODE,We examined nasal swabs and serum samples acquired from dromedary camels in Nigeria and Ethiopia during 2015–2017 for evidence of influenza virus infection. We detected antibodies against influenza A(H1N1) and A(H3N2) viruses and isolated an influenza A(H1N1)pdm09–like virus from a camel in Nigeria. Influenza surveillance in dromedary camels is needed.,2020 Jan,"['Chu, Daniel K.W.', 'Perera, Ranawaka A.P.M.', 'Ali, Abraham', 'Oladipo, Jamiu O.', 'Mamo, Gezahegne', 'So, Ray T.Y.', 'Zhou, Ziqi', 'Chor, Yen Yeen', 'Chan, Chak Kai', 'Belay, Desalegn', 'Tayachew, Adamu', 'Mengesha, Mesfin', 'Regassa, Feyesa', 'Lam, Nga Ting', 'Poon, Leo L.M.', 'Peiris, Malik']",Emerg Infect Dis,,,True
5147615c6992d89971127a86047fca6e01a86917,PMC,"Influenza A Virus Infections in Dromedary Camels, Nigeria and Ethiopia, 2015–2017",http://dx.doi.org/10.3201/eid2601.191165,PMC6924894,31855544,NO-CC CODE,We examined nasal swabs and serum samples acquired from dromedary camels in Nigeria and Ethiopia during 2015–2017 for evidence of influenza virus infection. We detected antibodies against influenza A(H1N1) and A(H3N2) viruses and isolated an influenza A(H1N1)pdm09–like virus from a camel in Nigeria. Influenza surveillance in dromedary camels is needed.,2020 Jan,"['Chu, Daniel K.W.', 'Perera, Ranawaka A.P.M.', 'Ali, Abraham', 'Oladipo, Jamiu O.', 'Mamo, Gezahegne', 'So, Ray T.Y.', 'Zhou, Ziqi', 'Chor, Yen Yeen', 'Chan, Chak Kai', 'Belay, Desalegn', 'Tayachew, Adamu', 'Mengesha, Mesfin', 'Regassa, Feyesa', 'Lam, Nga Ting', 'Poon, Leo L.M.', 'Peiris, Malik']",Emerg Infect Dis,,,True
da2fb4ffdc8824adeec5af4103d04667dc618b6a,PMC,In Memoriam: Jay Stephen Keystone (1943–2019),http://dx.doi.org/10.3201/eid2601.191500,PMC6924902,,NO-CC CODE,,2020 Jan,"Freedman, David O.",Emerg Infect Dis,,,True
45e91042ac20319b849f63a7dd00dda7d11de638,PMC,Hunters Searching among Starry Nights and at the Edges of Life,http://dx.doi.org/10.3201/eid2601.AC2601,PMC6924909,,NO-CC CODE,,2020 Jan,"Breedlove, Byron",Emerg Infect Dis,,,True
11a21be0569b11edf62c871f9e2561a2a5389006,PMC,"Influenza D Virus of New Phylogenetic Lineage, Japan",http://dx.doi.org/10.3201/eid2601.191092,PMC6924913,31855532,NO-CC CODE,Influenza D virus (IDV) can potentially cause respiratory diseases in livestock. We isolated a new IDV strain from diseased cattle in Japan; this strain is phylogenetically and antigenically distinguished from the previously described IDVs.,2020 Jan,"['Murakami, Shin', 'Sato, Ryota', 'Ishida, Hiroho', 'Katayama, Misa', 'Takenaka-Uema, Akiko', 'Horimoto, Taisuke']",Emerg Infect Dis,,,True
724be3f77bbbdcc7e73de43f4cfe22335ffb9ef9,PMC,"Influenza D Virus of New Phylogenetic Lineage, Japan",http://dx.doi.org/10.3201/eid2601.191092,PMC6924913,31855532,NO-CC CODE,Influenza D virus (IDV) can potentially cause respiratory diseases in livestock. We isolated a new IDV strain from diseased cattle in Japan; this strain is phylogenetically and antigenically distinguished from the previously described IDVs.,2020 Jan,"['Murakami, Shin', 'Sato, Ryota', 'Ishida, Hiroho', 'Katayama, Misa', 'Takenaka-Uema, Akiko', 'Horimoto, Taisuke']",Emerg Infect Dis,,,True
8f8eb4f004c2002face0723f2f58cc411954d36e,PMC,Complete Genome Sequence of Bordetella bronchiseptica Strain KM22,http://dx.doi.org/10.1128/MRA.01207-19,PMC6979298,31974149,NO-CC CODE,"Bordetella bronchiseptica isolate KM22 has been used in experimental infections of swine as a model of clinical B. bronchiseptica infection and to study host-to-host transmission. The draft genome sequence of KM22 was reported in 2014. Here, we report the complete genome sequence of KM22.",2020 Jan 23,"['Nicholson, Tracy L.', 'Bayles, Darrell O.', 'Shore, Sarah M.']",Microbiol Resour Announc,,,True
7685358860b9b2a9d1dd54d63813a4f115814b85,PMC,Safety of prone positioning in critically ill patients,http://dx.doi.org/10.5339/qmj.2019.qccc.60,PMC6984011,,NO-CC CODE,"Background: During the past two years, 5% of patients admitted to the Medical Intensive Care Unit (MICU) of Hamad General Hospital (HGH) had severe acute respiratory distress syndrome (ARDS) with a PaO(2)/FiO(2) ratio less than 100 mmHg. The risks associated with this condition include ventilator associated lung injury, over distension of lungs, and poor gas exchange which results in increased morbidity and mortality. With quality improvement initiatives like prone positioning, the mortality and morbidity associated with severe acute respiratory syndrome(1) can be reduced by improving hypoxemia(2) with a significant enhancement in PaO(2)/FiO(2) ratios while reducing injurious ventilation. Also, prone positioning can help prevent invasive interventions such as placing patients on extracorporeal membrane oxygenation (ECMO) therapy.(3) Methods: We evaluated the safety of prone positioning for improving hypoxemia in critically ill patients with PaO(2)/FiO(2) ratio < 100 mmHg to PaO(2)/FiO(2) ratio < 200 mmHg from 1(st) January 2017 to 31(st) December 2018, without major complications. Data collected included the PaO(2)/FiO(2) ratios based on arterial blood gases of mechanically ventilated patients before and after prone positioning. We were able to facilitate prone positioning in 72 out of 110 patients with severe ARDS having a total average PaO(2)/FiO(2) ratio of 84.4 ± 30 mmHg. The patients were proned for a maximum of 16 hours in each session where up to three sessions were incorporated. No major complications were encountered during the proning sessions. This was thought to be accomplished through the coordination of a dedicated multidisciplinary team, education and simulation classes for physicians, nurses, and respiratory therapists, following appropriate inclusion and exclusion criteria for prone positioning, and implementing quality measures through Plan-Do-Study-Act (PDSA) cycles as represented in Figure 1. Results: The total average PaO(2)/FiO(2) ratio before proning for 65% of patients (n = 72) with severe acute respiratory distress syndrome(4) was 84.4 ± 30 mmHg and after one hour of 16 hours proning, it improved to 180.3 ± 78 mmHg. The remaining 35% of patients either had traumatic fractures, unstable spinal injury, severe hemodynamic instability, or morbid obesity together with ARDS which made them unfavorable for prone positioning. Out of those who were proned, 11 (12.5%) patients did not have improvement in oxygenation after proning due to non-recruitable lungs and were put on ECMO. The PaO(2)/FiO(2) ratios before and after one hour of implementing the prone position technique in each quarter of 2017 and 2018 are represented in Figure 2. Conclusion: • Sustaining and standardizing the accomplished work of data collection. • Implementing the prone positioning technique across other critical care units of Hamad Medical Corporation. • Keeping a record of minor complications associated with prone positioning and resolving them in further sessions. • Documenting cases with contraindications to prone positioning.",2020 Jan 27,"['Akbar, Anzila', 'Albadw, Naseem', 'Racela, Brian', 'Damodaran, Chokkalinga', 'Mustafa, Emad', 'Coria, Roopa', 'Hassan, Ali', 'Saif Ibrahim, Abdulsalam']",Qatar Med J,,,True
25484d47cd99c0a59cfc9a6b8ab2514a3678417c,PMC,"Human Norovirus Infection in Dogs, Thailand",http://dx.doi.org/10.3201/eid2602.191151,PMC6986825,31961308,NO-CC CODE,"In July 2018, recombinant norovirus GII.Pe-GII.4 Sydney was detected in dogs who had diarrhea in a kennel and in children living on the same premises in Thailand. Whole-genome sequencing and phylogenetic analysis of 4 noroviruses from Thailand showed that the canine norovirus was closely related to human norovirus GII.Pe-GII.4 Sydney, suggesting human-to-canine transmission.",2020 Feb,"['Charoenkul, Kamonpan', 'Nasamran, Chanakarn', 'Janetanakit, Taveesak', 'Tangwangvivat, Ratanaporn', 'Bunpapong, Napawan', 'Boonyapisitsopa, Supanat', 'Suwannakarn, Kamol', 'Theamboonler, Apiradee', 'Chuchaona, Watchaporn', 'Poovorawan, Yong', 'Amonsin, Alongkorn']",Emerg Infect Dis,,,True
e70b0c3cfc63da354e09518073419ac8c670c89b,PMC,"Human Norovirus Infection in Dogs, Thailand",http://dx.doi.org/10.3201/eid2602.191151,PMC6986825,31961308,NO-CC CODE,"In July 2018, recombinant norovirus GII.Pe-GII.4 Sydney was detected in dogs who had diarrhea in a kennel and in children living on the same premises in Thailand. Whole-genome sequencing and phylogenetic analysis of 4 noroviruses from Thailand showed that the canine norovirus was closely related to human norovirus GII.Pe-GII.4 Sydney, suggesting human-to-canine transmission.",2020 Feb,"['Charoenkul, Kamonpan', 'Nasamran, Chanakarn', 'Janetanakit, Taveesak', 'Tangwangvivat, Ratanaporn', 'Bunpapong, Napawan', 'Boonyapisitsopa, Supanat', 'Suwannakarn, Kamol', 'Theamboonler, Apiradee', 'Chuchaona, Watchaporn', 'Poovorawan, Yong', 'Amonsin, Alongkorn']",Emerg Infect Dis,,,True
002f09dfc9a1323a15bf72e349d8b733ac97a2aa,PMC,Veiled Dangers in an Idyllic Setting,http://dx.doi.org/10.3201/eid2602.AC2602,PMC6986828,,NO-CC CODE,,2020 Feb,"Breedlove, Byron",Emerg Infect Dis,,,True
1dd2490b867180bd86c105c46fd880f9955f7ff8,PMC,"Porcine Deltacoronavirus Infection and Transmission in Poultry, United States",http://dx.doi.org/10.3201/eid2602.190346,PMC6986833,31961296,NO-CC CODE,"Coronaviruses cause respiratory and gastrointestinal diseases in diverse host species. Deltacoronaviruses (DCoVs) have been identified in various songbird species and in leopard cats in China. In 2009, porcine deltacoronavirus (PDCoV) was detected in fecal samples from pigs in Asia, but its etiologic role was not identified until 2014, when it caused major diarrhea outbreaks in swine in the United States. Studies have shown that PDCoV uses a conserved region of the aminopeptidase N protein to infect cell lines derived from multiple species, including humans, pigs, and chickens. Because PDCoV is a potential zoonotic pathogen, investigations of its prevalence in humans and its contribution to human disease continue. We report experimental PDCoV infection and subsequent transmission among poultry. In PDCoV-inoculated chicks and turkey poults, we observed diarrhea, persistent viral RNA titers from cloacal and tracheal samples, PDCoV-specific serum IgY antibody responses, and antigen-positive cells from intestines.",2020 Feb,"['Boley, Patricia A.', 'Alhamo, Moyasar A.', 'Lossie, Geoffrey', 'Yadav, Kush Kumar', 'Vasquez-Lee, Marcia', 'Saif, Linda J.', 'Kenney, Scott P.']",Emerg Infect Dis,,,True
791e42babcf7e8b6edf94918b034f15ce32ec402,PMC,Middle East Respiratory Syndrome Coronavirus Transmission,http://dx.doi.org/10.3201/eid2602.190697,PMC6986839,31961300,NO-CC CODE,"Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes a spectrum of respiratory illness, from asymptomatic to mild to fatal. MERS-CoV is transmitted sporadically from dromedary camels to humans and occasionally through human-to-human contact. Current epidemiologic evidence supports a major role in transmission for direct contact with live camels or humans with symptomatic MERS, but little evidence suggests the possibility of transmission from camel products or asymptomatic MERS cases. Because a proportion of case-patients do not report direct contact with camels or with persons who have symptomatic MERS, further research is needed to conclusively determine additional mechanisms of transmission, to inform public health practice, and to refine current precautionary recommendations.",2020 Feb,"['Killerby, Marie E.', 'Biggs, Holly M.', 'Midgley, Claire M.', 'Gerber, Susan I.', 'Watson, John T.']",Emerg Infect Dis,,,True
4b20966ea03c26a83c93f9786bf1f5bde3aa0cb0,PMC,Middle East Respiratory Syndrome Coronavirus Transmission,http://dx.doi.org/10.3201/eid2602.190697,PMC6986839,31961300,NO-CC CODE,"Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes a spectrum of respiratory illness, from asymptomatic to mild to fatal. MERS-CoV is transmitted sporadically from dromedary camels to humans and occasionally through human-to-human contact. Current epidemiologic evidence supports a major role in transmission for direct contact with live camels or humans with symptomatic MERS, but little evidence suggests the possibility of transmission from camel products or asymptomatic MERS cases. Because a proportion of case-patients do not report direct contact with camels or with persons who have symptomatic MERS, further research is needed to conclusively determine additional mechanisms of transmission, to inform public health practice, and to refine current precautionary recommendations.",2020 Feb,"['Killerby, Marie E.', 'Biggs, Holly M.', 'Midgley, Claire M.', 'Gerber, Susan I.', 'Watson, John T.']",Emerg Infect Dis,,,False
8e1eaa3b676ca8163c72106b913606f6aeccfc48,PMC,Social Responses to Epidemics Depicted by Cinema,http://dx.doi.org/10.3201/eid2602.181022,PMC6986850,,NO-CC CODE,"Films illustrate 2 ways that epidemics can affect societies: fear leading to a breakdown in sociability and fear stimulating preservation of tightly held social norms. The first response is often informed by concern over perceived moral failings within society, the second response by the application of arbitrary or excessive controls from outside the community.",2020 Feb,"['Han, Qijun', 'Curtis, Daniel R.']",Emerg Infect Dis,,,True
3ecf8a34e3a43ad60b934db992e34171e20659d9,PMC,Pseudoscience in medicine: cautionary recommendations,http://dx.doi.org/10.4314/ahs.v19i4.34,PMC7040346,32127888,NO-CC CODE,"INTRODUCTION: Certain real life applications of scientific and social science ideas that knowingly reject accumulated empirical biomedical evidence have been termed ‘pseudoscience,’ or empirical rejectionism. An uncritical acceptance of empiricism, or even of evidence-based medicine, however, can also be problematic. OBJECTIVES: With reference to a specific type of medical denialism associated with moral failure, justified by dissident AIDS and anti-vaccine scientific publications, this paper seeks to make the argument that this type of denialism meets certain longstanding definitions for classification as pseudoscience. METHODS: This paper uses a conceptual framework to make certain arguments and to juxtapose arguments for evidence-based approaches to medicine against literature that highlights certain limitations of an unquestioning approach to empiricism. RESULTS: Discussions of certain real life examples are used to derive the important insight that, under certain conditions, moral failure can result in the violation both Type I and Type II scientific error types, with catastrophic consequences. CONCLUSION: It is argued that the validity of all theory should not be assumed before sufficient empirical evidence has accumulated to support its validity across contexts. However, caution is required, to avoid the consequences of an unquestioning approach to empiricism.",2019 Dec,"Callaghan, Chris",Afr Health Sci,,,True
d4bff180d69fcc96bc31299183a498820fbca3ea,PMC,"A 25-Year-Old Sample Contributes the Complete Genome Sequence of Avian Coronavirus Vaccine Strain ArkDPI, Reisolated from Commercial Broilers in the United States",http://dx.doi.org/10.1128/MRA.00067-20,PMC7046816,32107295,NO-CC CODE,"Here, we report the complete genome sequence of Avian coronavirus strain ArkDPI of the GI-9 lineage, isolated from broiler chickens in North Georgia in 1994. This is the complete genome sequence of this vaccine strain, reisolated from broilers in the United States.",2020 Feb 27,"['Goraichuk, Iryna V.', 'Davis, James F.', 'Kulkarni, Arun B.', 'Afonso, Claudio L.', 'Suarez, David L.']",Microbiol Resour Announc,,,True
24dcca53dd31df074a77242d2e2e6053825e1761,PMC,Complete Genome Sequence of Avian Coronavirus Strain GA08 (GI-27 Lineage),http://dx.doi.org/10.1128/MRA.00068-20,PMC7046817,32107296,NO-CC CODE,"Avian coronavirus, also known as infectious bronchitis virus, is a highly contagious respiratory pathogen of chickens that is responsible for major economic losses to the poultry industry around the globe. Here, we report the complete genome sequence of strain GA08 of the GI-27 lineage, isolated from a fecal sample from a broiler chicken collected in Georgia in 2015.",2020 Feb 27,"['Goraichuk, Iryna V.', 'Davis, James F.', 'Kulkarni, Arun B.', 'Afonso, Claudio L.', 'Suarez, David L.']",Microbiol Resour Announc,,,True
,PMC,Opinion: Sustainable development must account for pandemic risk,http://dx.doi.org/10.1073/pnas.2001655117,PMC7049118,,,,,"['Di Marco, Moreno', 'Baker, Michelle L.', 'Daszak, Peter', 'De Barro, Paul', 'Eskew, Evan A.', 'Godde, Cecile M.', 'Harwood, Tom D.', 'Herrero, Mario', 'Hoskins, Andrew J.', 'Johnson, Erica', 'Karesh, William B.', 'Machalaba, Catherine', 'Garcia, Javier Navarro', 'Paini, Dean', 'Pirzl, Rebecca', 'Smith, Mark Stafford', 'Zambrana-Torrelio, Carlos', 'Ferrier, Simon']",,,,
,PMC,Latest updates on COVID-19 from the European Centre for Disease Prevention and Control,http://dx.doi.org/10.2807/1560-7917.ES.2020.25.6.2002131,PMC7029450,32070466,CC BY,,2020 Feb 13,,Euro Surveill,,,
,PMC,Erratum for Euro Surveill. 2020;25(5),http://dx.doi.org/10.2807/1560-7917.ES.2020.25.6.2002132,PMC7029446,32070469,CC BY,,2020 Feb 13,,Euro Surveill,,,
,PMC,Which lessons shall we learn from the 2019 novel coronavirus outbreak?,http://dx.doi.org/10.21037/atm.2020.02.06,PMC7036635,,,,,"['Mattiuzzi, Camilla', 'Lippi, Giuseppe']",,,,
,PMC,Chinese expert consensus on the perinatal and neonatal management for the prevention and control of the 2019 novel coronavirus infection (First edition),http://dx.doi.org/10.21037/atm.2020.02.20,PMC7036629,,,"Since December 2019, there has been an outbreak of novel coronavirus (2019-nCoV) infection in China. Two cases of neonates with positive 2019-nCoV tests have been reported. Due to the immature immune system and the possibility of vertical transmission from mother to infant, neonates have become a high-risk group susceptible to 2019-nCoV, which emphasize a close cooperation from both perinatal and neonatal pediatrics. In neonatal intensive care unit (NICU), to prevent and control infection, there should be practical measures to ensure the optimal management of children potentially to be infected. According to the latest 2019-nCoV national management plan and the actual situation, the Chinese Neonatal 2019-nCoV expert working Group has put forward measures on the prevention and control of neonatal 2019-nCoV infection.",,"['Wang, Laishuan', 'Shi, Yuan', 'Xiao, Tiantian', 'Fu, Jianhua', 'Feng, Xing', 'Mu, Dezhi', 'Feng, Qi', 'Hei, Mingyan', 'Hu, Xiaojing', 'Li, Zhankui', 'Lu, Guoping', 'Tang, Zezhong', 'Wang, Yajuan', 'Wang, Chuanqing', 'Xia, Shiwen', 'Xu, Jianqing', 'Yang, Yujia', 'Yang, Jie', 'Zeng, Mei', 'Zheng, Jun', 'Zhou, Wei', 'Zhou, Xiaoyu', 'Zhou, Xiaoguang', 'Du, Lizhong', 'Lee, Shoo K.', 'Zhou, Wenhao', None]",,,,
,PMC,Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia,http://dx.doi.org/10.21037/tp.2020.02.06,PMC7036645,,,"BACKGROUND: The newly identified 2019-nCoV, which appears to have originated in Wuhan, the capital city of Hubei province in central China, is spreading rapidly nationwide. A number of cases of neonates born to mothers with 2019-nCoV pneumonia have been recorded. However, the clinical features of these cases have not been reported, and there is no sufficient evidence for the proper prevention and control of 2019-nCoV infections in neonates. METHODS: The clinical features and outcomes of 10 neonates (including 2 twins) born to 9 mothers with confirmed 2019-nCoV infection in 5 hospitals from January 20 to February 5, 2020 were retrospectively analyzed. RESULTS: Among these 9 pregnant women with confirmed 2019-nCoV infection, onset of clinical symptoms occurred before delivery in 4 cases, on the day of delivery in 2 cases, and after delivery in 3 cases. In most cases, fever and a cough were the first symptoms experienced, and 1 patient also had diarrhea. Of the newborns born to these mothers, 8 were male and 2 were female; 4 were full-term infants and 6 were born premature; 2 were small-for-gestational-age (SGA) infants and 1 was a large-for-gestational-age (LGA) infant; there were 8 singletons and 2 twins. Of the neonates, 6 had a Pediatric Critical Illness Score (PCIS) score of less than 90. Clinically, the first symptom in the neonates was shortness of breath (n=6), but other initial symptoms such as fever (n=2), thrombocytopenia accompanied by abnormal liver function (n=2), rapid heart rate (n=1), vomiting (n=1), and pneumothorax (n=1) were observed. Up to now, 5 neonates have been cured and discharged, 1 has died, and 4 neonates remain in hospital in a stable condition. Pharyngeal swab specimens were collected from 9 of the 10 neonates 1 to 9 days after birth for nucleic acid amplification tests for 2019-nCoV, all of which showed negative results. CONCLUSIONS: Perinatal 2019-nCoV infection may have adverse effects on newborns, causing problems such as fetal distress, premature labor, respiratory distress, thrombocytopenia accompanied by abnormal liver function, and even death. However, vertical transmission of 2019-nCoV is yet to be confirmed.",,"['Zhu, Huaping', 'Wang, Lin', 'Fang, Chengzhi', 'Peng, Sicong', 'Zhang, Lianhong', 'Chang, Guiping', 'Xia, Shiwen', 'Zhou, Wenhao']",,,,
,PMC,Three Amino Acid Changes in Avian Coronavirus Spike Protein Allow Binding to Kidney Tissue,http://dx.doi.org/10.1128/JVI.01363-19,PMC6955270,31694947,CC BY,"Infectious bronchitis virus (IBV) infects ciliated epithelial cells in the chicken respiratory tract. While some IBV strains replicate locally, others can disseminate to various organs, including the kidney. Here, we elucidate the determinants for kidney tropism by studying interactions between the receptor-binding domain (RBD) of the viral attachment protein spike from two IBV strains with different tropisms. Recombinantly produced RBDs from the nephropathogenic IBV strain QX and from the nonnephropathogenic strain M41 bound to the epithelial cells of the trachea. In contrast, only QX-RBD binds more extensively to cells of the digestive tract, urogenital tract, and kidneys. While removal of sialic acids from tissues prevented binding of all proteins to all tissues, binding of QX-RBD to trachea and kidney could not be blocked by preincubation with synthetic alpha-2,3-linked sialic acids. The lack of binding of QX-RBD to a previously identified IBV-M41 receptor was confirmed by enzyme-linked immunosorbent assay (ELISA), demonstrating that tissue binding of QX-RBD is dependent on a different sialylated glycan receptor. Using chimeric RBD proteins, we discovered that the region encompassing amino acids 99 to 159 of QX-RBD was required to establish kidney binding. In particular, QX-RBD amino acids 110 to 112 (KIP) were sufficient to render IBV-M41 with the ability to bind to kidney, while the reciprocal mutations in IBV-QX abolished kidney binding completely. Structural analysis of both RBDs suggests that the receptor-binding site for QX is located at a different location on the spike than that of M41. IMPORTANCE Infectious bronchitis virus is the causative agent of infectious bronchitis in chickens. Upon infection of chicken flocks, the poultry industry faces substantial economic losses by diminished egg quality and increased morbidity and mortality of infected animals. While all IBV strains infect the chicken respiratory tract via the ciliated epithelial layer of the trachea, some strains can also replicate in the kidneys, dividing IBV into the following two pathotypes: nonnephropathogenic (example, IBV-M41) and nephropathogenic viruses (including IBV-QX). Here, we set out to identify the determinants for the extended nephropathogenic tropism of IBV-QX. Our data reveal that each pathotype makes use of a different sialylated glycan ligand, with binding sites on opposite sides of the attachment protein. This knowledge should facilitate the design of antivirals to prevent coronavirus infections in the field.",2020 Jan 6,"['Bouwman, Kim M.', 'Parsons, Lisa M.', 'Berends, Alinda J.', 'de Vries, Robert P.', 'Cipollo, John F.', 'Verheije, Monique H.']",J Virol,,,
,PMC,Cryo-EM analysis of a feline coronavirus spike protein reveals a unique structure and camouflaging glycans,http://dx.doi.org/10.1073/pnas.1908898117,PMC6983407,,,"Feline infectious peritonitis virus (FIPV) is an alphacoronavirus that causes a nearly 100% mortality rate without effective treatment. Here we report a 3.3-Å cryoelectron microscopy (cryo-EM) structure of the serotype I FIPV spike (S) protein, which is responsible for host recognition and viral entry. Mass spectrometry provided site-specific compositions of densely distributed high-mannose and complex-type N-glycans that account for 1/4 of the total molecular mass; most of the N-glycans could be visualized by cryo-EM. Specifically, the N-glycans that wedge between 2 galectin-like domains within the S1 subunit of FIPV S protein result in a unique propeller-like conformation, underscoring the importance of glycosylation in maintaining protein structures. The cleavage site within the S2 subunit responsible for activation also showed distinct structural features and glycosylation. These structural insights provide a blueprint for a better molecular understanding of the pathogenesis of FIP.",,"['Yang, Tzu-Jing', 'Chang, Yen-Chen', 'Ko, Tzu-Ping', 'Draczkowski, Piotr', 'Chien, Yu-Chun', 'Chang, Yuan-Chih', 'Wu, Kuen-Phon', 'Khoo, Kay-Hooi', 'Chang, Hui-Wen', 'Hsu, Shang-Te Danny']",,,,
,PMC,Pathogen reduction of blood components during outbreaks of infectious diseases in the European Union: an expert opinion from the European Centre for Disease Prevention and Control consultation meeting,http://dx.doi.org/10.2450/2019.0288-19,PMC6917531,,,"Pathogen reduction (PR) of selected blood components is a technology that has been adopted in practice in various ways. Although they offer great advantages in improving the safety of the blood supply, these technologies have limitations which hinder their broader use, e.g. increased costs. In this context, the European Centre for Disease Prevention and Control (ECDC), in co-operation with the Italian National Blood Centre, organised an expert consultation meeting to discuss the potential role of pathogen reduction technologies (PRT) as a blood safety intervention during outbreaks of infectious diseases for which (in most cases) laboratory screening of blood donations is not available. The meeting brought together 26 experts and representatives of national competent authorities for blood from thirteen European Union and European Economic Area (EU/EEA) Member States (MS), Switzerland, the World Health Organization, the European Directorate for the Quality of Medicines and Health Care of the Council of Europe, the US Food and Drug Administration, and the ECDC. During the meeting, the current use of PRTs in the EU/EEA MS and Switzerland was verified, with particular reference to emerging infectious diseases (see Appendix). In this article, we also present expert discussions and a common view on the potential use of PRT as a part of both preparedness and response to threats posed to blood safety by outbreaks of infectious disease.",,"['Domanović, Dragoslav', 'Ushiro-Lumb, Ines', 'Compernolle, Veerle', 'Brusin, Sergio', 'Funk, Markus', 'Gallian, Pierre', 'Georgsen, Jørgen', 'Janssen, Mart', 'Jimenez-Marco, Teresa', 'Knutson, Folke', 'Liumbruno, Giancarlo M.', 'Mali, Polonca', 'Marano, Giuseppe', 'Maryuningsih, Yuyun', 'Niederhauser, Christoph', 'Politis, Constantina', 'Pupella, Simonetta', 'Rautmann, Guy', 'Saadat, Karmin', 'Sandid, Imad', 'Sousa, Ana P.', 'Vaglio, Stefania', 'Velati, Claudio', 'Verdun, Nicole', 'Vesga, Miguel', 'Rebulla, Paolo']",,,,
,PMC,Porcine Reproductive and Respiratory Syndrome Virus Enhances Self-Replication via AP-1–Dependent Induction of SOCS1,http://dx.doi.org/10.4049/jimmunol.1900731,PMC6943376,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) has caused tremendous economic losses in the swine industry since its emergence in the late 1980s. PRRSV exploits various strategies to evade immune responses and establish chronic persistent infections. Suppressor of cytokine signaling (SOCS) 1, a member of the SOCS family, is a crucial intracellular negative regulator of innate immunity. In this study, it was shown that SOCS1 can be co-opted by PRRSV to evade host immune responses, facilitating viral replication. It was observed that PRRSV induced SOCS1 production in porcine alveolar macrophages, monkey-derived Marc-145 cells, and porcine-derived CRL2843-CD163 cells. SOCS1 inhibited the expression of IFN-β and IFN-stimulated genes, thereby markedly enhancing PRRSV replication. It was observed that the PRRSV N protein has the ability to upregulate SOCS1 production and that nuclear localization signal–2 (NLS-2) is essential for SOCS1 induction. Moreover, SOCS1 upregulation was dependent on p38/AP-1 and JNK/AP-1 signaling pathways rather than classical type I IFN signaling pathways. In summary, to our knowledge, the findings of this study uncovered the molecular mechanism that underlay SOCS1 induction during PRRSV infection, providing new insights into viral immune evasion and persistent infection.",,"['Luo, Xuegang', 'Chen, Xin-xin', 'Qiao, Songlin', 'Li, Rui', 'Xie, Sha', 'Zhou, Xinyu', 'Deng, Ruiguang', 'Zhou, En-min', 'Zhang, Gaiping']",,,,
,PMC,"Meeting report: Global vaccine and immunization research forum, 2018",http://dx.doi.org/10.1016/j.vaccine.2019.10.011,PMC6899432,31623915,CC BY,"Every two years, the Global Vaccine and Immunization Research Forum takes stock of global research in vaccines and immunization. As in prior years, the 2018 meeting addressed vaccine discovery, development, decision-making, and deployment. This time, however, it also featured two overarching themes: “Innovating for Equity” and “End-to-End Integration.” Significant advances have been made in the last two years, but participants noted that some important goals of the Global Vaccine Action Plan are not being met and called urgently for innovation in improving access to vaccines. Two factors were highlighted as crucial to improving coverage: a focus on equity and sustainability throughout the immunization ecosystem, and an enabling political environment that prioritizes health and immunization.",2019 Dec 10,"['Dull, Peter', 'Friede, Martin', 'Hwang, Angela', 'Hall, B. Fenton']",Vaccine,,,
,PMC,Innate Immunity of the Lung,http://dx.doi.org/10.1159/000504621,PMC6959115,,,,,"['Greene, Catherine M.', 'Hiemstra, Pieter S.']",,,,
,PMC,Endocarditis due to Neisseria elongata: A case report and review of the literature,http://dx.doi.org/10.18683/germs.2019.1176,PMC6942657,,,"INTRODUCTION: Neisseria elongata, which is part of the normal oropharyngeal bacterial flora, can be an aggressive organism causing serious infections including infective endocarditis. N. elongata infective endocarditis is rare and no current guidelines exist to direct antibiotic selection and/or duration of treatment. CASE REPORT: We report a case of infective endocarditis due to N. elongata and a review of the literature. Our patient is a healthy young woman, who was found to have an aortic root abscess with valve perforation requiring valve replacement. DISCUSSION: N. elongata infective endocarditis typically affects the left cardiac chambers and is associated with high risk of embolization. A transesophageal echocardiogram should be performed as part of the initial workup to assess the extent of infection, as a high percentage of patients develop perivalvular abscess formation and/or valve perforation. Most patients require prolonged antibiotic therapy and early surgical intervention. CONCLUSIONS: This case demonstrates the potential severity of N. elongata endocarditis. Further studies are needed to establish management guidance.",,"['Youssef, Dima', 'Marroush, Tariq S.', 'Levine, Miriam T.', 'Sharma, Mamta']",,,,
,PMC,Analysis of the Microbiome in the Adenoids of Korean Children with Otitis Media with Effusion,http://dx.doi.org/10.5152/iao.2019.6650,PMC6937193,,,"OBJECTIVES: The adenoid pad, which is located between the orifice of the Eustachian tube (ET) and posterior nasal cavity, can affect the development of otitis media with effusion (OME) because of its anatomical location. The aim of the present study was to evaluate adenoid microbial colonization through 16S ribosomal RNA (rRNA) pyrosequencing, an advanced molecular technique, and to document the relationship with OME. MATERIALS AND METHODS: Adenoid samples were collected using sterile cotton from 32 children during ventilation tube insertion. Sixteen children with OME who underwent tonsillectomy and adenoidectomy due to obstructive symptoms were assigned to the OME group and sixteen children without OME were assigned to the control group. We performed a 16S rRNA-based culture-independent survey of bacterial communities using the MiSeq platform. RESULTS: The diversity index, mean operational taxonomic units, and Shannon index were lower in the OME group than those in the control group. A taxonomic analysis showed differences in microbiota distribution between the OME and control groups at the phylum, genus, and species levels. The analysis, which was based on weighted UniFrac distances, revealed differences in microbial composition between the two groups. CONCLUSION: Bacterial community analysis using 16S rRNA pyrosequencing allows us to understand the relationship between the microbial communities of adenoids and the development of OME better.",,"['Kim, Sung Kyun', 'Hong, Seok Jin', 'Pak, Kyung Ho', 'Hong, Seok Min']",,,,
,PMC,Characterisation of Crandell-Rees Feline Kidney (CRFK) cells as mesenchymal in phenotype,http://dx.doi.org/10.1016/j.rvsc.2019.10.012,PMC6863388,31683198,CC BY-NC-ND,"The Crandell-Rees Feline Kidney Cell (CRFK) is an immortalised cell line derived from the feline kidney that is utilised for the growth of certain vaccinal viruses. Confusion exists as to whether CRFK are epithelial or mesenchymal in phenotype. The aim of this study was to characterise CRFK cells via immunofluorescence, enzyme cytochemistry, western blotting, RT-qPCR for S100A4 and comparison to primary feline proximal tubular epithelial cells (FPTEC) and feline cortical fibroblasts (FCF). CRFK cells were of fusiform morphology and appeared similar to FCF. CRFK expressed the mesenchymal intermediate filament (IF) protein vimentin together with two cell adhesion molecules associated with feline fibroblasts (CD29 and CD44), and lacked expression of the epithelial IF cytokeratin, myogenic IF desmin and endothelial marker von Willebrand factor (vWF). In addition, CRFK did not demonstrate brush border enzyme activity typical of FPTEC. S100A4 gene expression, implicated in both neoplastic transformation and epithelial to mesenchymal transition, was highly upregulated in CRFK in comparison to the primary feline renal cells. CRFK appear phenotypically similar to fibroblasts, rather than tubular epithelial cells, and may have undergone neoplastic transformation or epithelial-to-mesenchymal transition after extensive passaging. This finding may have potential implications for future research utilising this cell line.",2019 Dec,"['Lawson, J.S.', 'Syme, H.M.', 'Wheeler-Jones, C.P.D.', 'Elliott, J.']",Res Vet Sci,,,
,PMC,Etiological characteristics of influenza-like illness in Jiangsu province from 2012 to 2016,http://dx.doi.org/10.7555/JBR.33.20180128,PMC6891875,,,"Influenza-like illness (ILI) is an acute respiratory infection caused by various pathogens. However, the epidemiologic characteristics of ILI pathogens in Jiangsu province are unclear. To better understand the ILI etiology, the characteristics of the pathogens from nasopharyngeal swab samples of patients with ILI collected from 2012 to 2016 in 6 hospitals in Jiangsu province were studied. The pathogens, including influenza virus, respiratory syncytial virus (RSV), rhinovirus (HRV), adenovirus (ADV), herpes simplex virus (HSV), human coronavirus (hCoV), Streptococcus pneumoniae and Haemophilus influenzae, were detected by real-time PCR. At least one pathogen was identified in 1 334 of the patients (40.23%). Among viruses, HRV, influenza A virus (Flu A), ADV and RSV were the most frequently detected. ADV was the only pathogen that was distributed evenly in different years and regions (P>0.05). The etiological distribution varied in different age groups.Streptococcus pneumoniae was the most common pathogen in co-infections with a co-detection rate of 64.57% (319/494). The spectrum of etiologies could help to estimate disease burden and provide guidance for vaccination.",,"['Xu, Ke', 'Huo, Xiang', 'Zu, Rongqiang', 'Wang, Shenjiao', 'Qin, Yuanfang', 'Dai, Qigang', 'Qi, Xian', 'Yu, Huiyan', 'Chen, Lilin', 'Hong, Lei', 'Xu, Yangting', 'Yi, Qianhua', 'Wang, Weixiang', 'Wang, Xuan', 'Dai, Wenjun', 'Zha, Jie', 'Han, Weining', 'Bao, Changjun']",,,,
,PMC,Gelatin filter capture-based high-throughput sequencing analysis of microbial diversity in haze particulate matter,http://dx.doi.org/10.7555/JBR.33.20180121,PMC6891871,,,"Airborne particulate matter (PM), especially PM(2.5), can be easily adsorbed by human respiratory system. Their roles in carrying pathogens for spreading epidemic diseases has attracted great concern. Herein, we developed a novel gelatin filter-based and culture-independent method for investigation of the microbial diversity in PM samples during a haze episode in Tianjin, China. This method involves particle capture by gelatin filters, filter dissolution for DNA extraction, and high-throughput sequencing for analysis of the microbial diversity. A total of 584 operational taxonomic units (OTUs) of bacteria and 370 OTUs of fungi at the genus level were identified during hazy days. The results showed that both bacterial and fungal diversities could be evaluated by this method. This study provides a convenient strategy for investigation of microbial biodiversity in haze, facilitating accurate evaluation of airborne epidemic diseases.",,"['Sun, Meiqing', 'Ding, Zhanlin', 'Wang, Hong', 'Yu, Guangping', 'Feng, Zhe', 'Li, Bingzhi', 'Li, Penghui']",,,,
,PMC,Molecular epidemiology of respiratory viruses among Malaysian Young children with a confirmed respiratory infection during 2014–2015,http://dx.doi.org/10.21037/jtd.2019.10.69,PMC6940242,,,"BACKGROUND: In many developing countries, acute respiratory tract infections (ARTIs) are the main cause of morbidity and mortality among young children. This study aims to evaluate the molecular epidemiology of respiratory viruses among Malaysian children with confirmed respiratory infections between July 2014 and July 2015. METHODS: A total of 394 nasopharyngeal swabs were collected prospectively from children age 0–5 years old with ARTIs from hospitals in Kuala Lumpur. Respiratory viral panel (RVP) assay was used to identify the viral aetiology of respiratory infections. RESULTS: From a total of 394 samples, the positive detection rate was 79.9% (n=315). A total of 15 types of RNA viruses and a single type of DNA virus were detected. Enterovirus/rhinovirus (n=112, 28.4%), respiratory syncytial virus (RSV) (n=85, 21.6%), adenovirus (n=64, 16.2%), human bocavirus (n=34, 8.6%), and human metapneumovirus (n=29, 7.4%) were the five predominant viruses. Enterovirus/rhinovirus and RSV constituted most of the viral respiratory infections among young children, especially among children less than 1 year old. No coronavirus was detected among children between 3 and 5 years old. Co-infection caused by 2 or 3 respiratory viruses were detected in 52 patients (13.2%). Enterovirus/rhinovirus, adenovirus, and human bocavirus demonstrated pronounced seasonality. The infection rate peaked during mid-year, while the lowest activity occurred during early of the year. CONCLUSIONS: The use of molecular assay as a routine diagnostic in the hospitals can improve the diagnosis and management of respiratory tract infections among children.",,"['Yew, Su Mei', 'Tan, Ka-Liong', 'Yeo, Siok Koon', 'Ng, Kee Peng', 'Kuan, Chee Sian']",,,,
,PMC,To TRIM or not to TRIM: the balance of host–virus interactions mediated by the ubiquitin system,http://dx.doi.org/10.1099/jgv.0.001341,PMC7011758,,,"The innate immune system responds rapidly to protect against viral infections, but an overactive response can cause harmful damage. To avoid this, the response is tightly regulated by post-translational modifications (PTMs). The ubiquitin system represents a powerful PTM machinery that allows for the reversible linkage of ubiquitin to activate and deactivate a target’s function. A precise enzymatic cascade of ubiquitin-activating, conjugating and ligating enzymes facilitates ubiquitination. Viruses have evolved to take advantage of the ubiquitin pathway either by targeting factors to dampen the antiviral response or by hijacking the system to enhance their replication. The tripartite motif (TRIM) family of E3 ubiquitin ligases has garnered attention as a major contributor to innate immunity. Many TRIM family members limit viruses either indirectly as components in innate immune signalling, or directly by targeting viral proteins for degradation. In spite of this, TRIMs and other ubiquitin ligases can be appropriated by viruses and repurposed as valuable tools in viral replication. This duality of function suggests a new frontier of research for TRIMs and raises new challenges for discerning the subtleties of these pro-viral mechanisms. Here, we review current findings regarding the involvement of TRIMs in host–virus interactions. We examine ongoing developments in the field, including novel roles for unanchored ubiquitin in innate immunity, the direct involvement of ubiquitin ligases in promoting viral replication, recent controversies on the role of ubiquitin and TRIM25 in activation of the pattern recognition receptor RIG-I, and we discuss the implications these studies have on future research directions.",,"['Hage, Adam', 'Rajsbaum, Ricardo']",,,,
,PMC,Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection,http://dx.doi.org/10.1172/jci.insight.131774,PMC6824443,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 in Saudi Arabia and has caused over 2400 cases and more than 800 deaths. Epidemiological studies identified diabetes as the primary comorbidity associated with severe or lethal MERS-CoV infection. Understanding how diabetes affects MERS is important because of the global burden of diabetes and pandemic potential of MERS-CoV. We used a model in which mice were made susceptible to MERS-CoV by expressing human DPP4, and type 2 diabetes was induced by administering a high-fat diet. Upon infection with MERS-CoV, diabetic mice had a prolonged phase of severe disease and delayed recovery that was independent of virus titers. Histological analysis revealed that diabetic mice had delayed inflammation, which was then prolonged through 21 days after infection. Diabetic mice had fewer inflammatory monocyte/macrophages and CD4(+) T cells, which correlated with lower levels of Ccl2 and Cxcl10 expression. Diabetic mice also had lower levels of Tnfa, Il6, Il12b, and Arg1 expression and higher levels of Il17a expression. These data suggest that the increased disease severity observed in individuals with MERS and comorbid type 2 diabetes is likely due to a dysregulated immune response, which results in more severe and prolonged lung pathology.",,"['Kulcsar, Kirsten A.', 'Coleman, Christopher M.', 'Beck, Sarah E.', 'Frieman, Matthew B.']",,,,
,PMC,Innate Immune Evasion by Human Respiratory RNA Viruses,http://dx.doi.org/10.1159/000503030,PMC6959104,,,"The impact of respiratory virus infections on the health of children and adults can be very significant. Yet, in contrast to most other childhood infections as well as other viral and bacterial diseases, prophylactic vaccines or effective antiviral treatments against viral respiratory infections are either still not available, or provide only limited protection. Given the widespread prevalence, a general lack of natural sterilizing immunity, and/or high morbidity and lethality rates of diseases caused by influenza, respiratory syncytial virus, coronaviruses, and rhinoviruses, this difficult situation is a genuine societal challenge. A thorough understanding of the virus-host interactions during these respiratory infections will most probably be pivotal to ultimately meet these challenges. This review attempts to provide a comparative overview of the knowledge about an important part of the interaction between respiratory viruses and their host: the arms race between host innate immunity and viral innate immune evasion. Many, if not all, viruses, including the respiratory viruses listed above, suppress innate immune responses to gain a window of opportunity for efficient virus replication and setting-up of the infection. The consequences for the host's immune response are that it is often incomplete, delayed or diminished, or displays overly strong induction (after the delay) that may cause tissue damage. The affected innate immune response also impacts subsequent adaptive responses, and therefore viral innate immune evasion often undermines fully protective immunity. In this review, innate immune responses relevant for respiratory viruses with an RNA genome will briefly be summarized, and viral innate immune evasion based on shielding viral RNA species away from cellular innate immune sensors will be discussed from different angles. Subsequently, viral enzymatic activities that suppress innate immune responses will be discussed, including activities causing host shut-off and manipulation of stress granule formation. Furthermore, viral protease-mediated immune evasion and viral manipulation of the ubiquitin system will be addressed. Finally, perspectives for use of the reviewed knowledge for the development of novel antiviral strategies will be sketched.",,"Kikkert, Marjolein",,,,
,PMC,"Preventing Emerging and Re-emerging Infections in the Eastern Mediterranean Region: Gaps, Challenges, and Priorities",http://dx.doi.org/10.2196/14348,PMC6811772,31599734,CC BY,"BACKGROUND: The Eastern Mediterranean Public Health Network, supported by the Biosecurity Engagement Program, contributed significantly to strengthening the preparedness and response to the emerging and re-emerging infections in the region. OBJECTIVE: This study aimed to determine the gaps, challenges, and priorities for preventing the emerging and re-emerging infections, with a focus on biosafety and biosecurity in four countries of the region, namely, Egypt, Iraq, Jordan, and Morocco. METHODS: A total of two different methods were used to determine the gaps and priorities for preventing the emerging and re-emerging infections. The first method was a rapid assessment for the preparedness and response to the emerging and re-emerging infections in four countries of the region, with a focus on biosafety and biosecurity. The second method was a face-to-face round table meeting of the participating teams for two days, where the teams from all countries presented their countries’ profiles, findings, priorities, and gaps based on the countries’ assessments. RESULTS: The assessment and meeting resulted in several priorities and recommendations for each of the countries in the areas of legislation and coordination, biosafety and biosecurity, surveillance and human resources, case management and response, infection control and prevention, and risk communication and laboratory capacity. CONCLUSIONS: Many recommendations were relatively consistent throughout, including improving communication or building collaborations to improve the overall health of the country.",2019 Oct 9,"['Araj, Rawan', 'Alqasrawi, Sultan', 'Samy, Sahar', 'Alwahdanee, Ghaya', 'Wadi, Jamal', 'Mofleh, Jawad', 'Alsanouri, Tarek']",JMIR Public Health Surveill,,,
,PMC,"Assessment of Temporary Community-Based Health Care Facilities During Arbaeenia Mass Gathering at Karbala, Iraq: Cross-Sectional Survey Study",http://dx.doi.org/10.2196/10905,PMC6800459,31588911,CC BY,"BACKGROUND: Arbaeenia mass gathering (MG) in Karbala, Iraq, is becoming one of the largest MGs in the world. The health care infrastructure in Iraq is inadequately prepared to serve the health needs of the millions of pilgrims. OBJECTIVE: This study aimed to describe the temporary health care facilities installed and run by the local community to provide health care services to Arbaeenia pilgrims in Karbala, Iraq. METHODS: A survey was conducted in all community-based health care facilities located along part of Najaf to Karbala road within Karbala governorate. A structured questionnaire was answered through an interview with the workers and direct observation. Data were collected on staff profile, type of services provided, use of basic infection control measures, medical equipment, drugs and supplies, and the most commonly encountered medical problems. RESULTS: The total number of health care facilities was 120, staffed by 659 workers. Only 18 (15.0%, 18/120) facilities were licensed, and 44.1% (53/120) of the workers were health professionals. The health care workers provided different services including dispensing drugs (370/1692, 21.87%), measuring blood pressure and blood sugar (350/1692, 20.69%), and caring for wounds and injuries (319/1692, 18.85%). Around 97% (116/120) health facilities provided services for musculoskeletal disorders and only 16.7% (20/120) provided services for injuries. The drugs available in the clinic were analgesics, drugs for gastrointestinal and respiratory diseases, and antibiotics, with an availability range of 13.3% to 100.0%. Infection control practices for individual protection, environmental sanitation, and medical waste disposal were available in a range of 18.1% to 100.0%. CONCLUSIONS: Community-based health care facilities experienced a profound shortage of trained human resources and medical supplies. They can significantly contribute to health services if they are adequately equipped and follow standardized operation procedures.",2019 Oct 4,"['Lami, Faris', 'Hameed, Inam', 'Arbaji, Ali']",JMIR Public Health Surveill,,,
,PMC,25-HC promotes hepatocellular carcinoma metastasis through up-regulation of TLR4 dependent FABP4,,PMC6834473,,,"Metabolic syndrome is a significant risk factor for the development of hepatocellular carcinoma (HCC). 25-HC (25-hydroxycholesterol) synthesized from cholesterol plays an important role in lipid metabolism. However, the functions and mechanism of 25-HC in HCC remain largely unknown. In this study, we demonstrated that 25-HC promoted HCC cells migration and intrahepatic and extrahepatic metastasis while did not affect the cells proliferation and apoptosis. Mechanistically, the promotive effect of 25-HC was through up-regulation of Toll-like receptor 4 (TLR4) dependent fatty acid binding protein 4 (FABP4). Inhibition of FABP4 hindered 25-HC-induced cells migration and metastasis. Moreover, up-regulation of FABP4 was observed in HCC tissues from database analysis. In summary, our study reveals the effects and mechanism of 25-HC/TLR4/FABP4 axis in promoting HCC metastasis, which provides novel avenue for therapeutic intervention against HCC progression.",,"['Wang, Saisai', 'Yao, Yuanyuan', 'Wang, Xiao', 'Zheng, Gang', 'Ouyang, Wei', 'Chen, Wenbin']",,,,
,PMC,Successful 5-fluorouracil (5-FU) infusion re-challenge in a metastatic colorectal cancer patient with coronary artery disease who experienced symptoms consistent with coronary vasospasm during first 5-FU infusion,http://dx.doi.org/10.21037/jgo.2019.07.04,PMC6776815,,,"5-fluorouracil (5-FU) is an important component of chemotherapy for metastatic colon cancer and can be administered as an intravenous infusion or bolus. Coronary vasospasm is a known complication of infusional and bolus 5-FU administration. In patients who experience coronary vasospasm, 5-FU is often discontinued. Several cases of successful re-challenge with bolus 5-FU, utilizing calcium channel blockers (CCBs) and nitrates to prophylaxis against coronary vasospasm recurrence, have been reported in the literature. However, since there is increased variability of time to symptom onset with infusional 5-FU, re-challenge with infusional 5-FU has not been widely studied. Given potential differences in the toxicity profile and exposure time, infusional may be more appropriate than bolus for some patients. Here we report successful re-challenge with infusional 5-FU, following coronary vasospasm during the first cycle of 5-FU plus leucovorin plus oxaliplatin chemotherapy, in a patient with metastatic colon cancer and coronary artery disease (CAD). The 5-FU re-challenge plan included dose reduction, CCB and nitrate prophylaxis, and telemetry monitoring.",,"['Redman, Jason M.', 'Rhea, Logan P.', 'Brofferio, Alessandra', 'Whelpley, Margaret', 'Gulley, James L.', 'Gatti-Mays, Margaret E.', 'McMahon, Sheri', 'Cordes, Lisa M.', 'Strauss, Julius']",,,,
,PMC,Spectrum of respiratory viral infections in liver disease patients with cirrhosis admitted in critical care unit,http://dx.doi.org/10.4103/JLP.JLP_6_19,PMC6943874,31929704,CC BY-NC-SA,"BACKGROUND: Clinical significance of respiratory viruses (RVs) as an etiology of pneumonia in liver disease patients with cirrhosis is usually underestimated. Therefore, the aim of this study was to evaluate the spectrum of RVs in cirrhotic patients with pneumonia admitted in critical care units (CCUs) and its impact on the clinical outcome of cirrhotic patients. MATERIAL AND METHOD: A prospective study was conducted in a tertiary care CCU, and consecutive cirrhotic patients with pneumonia were included. Bronchoalveolar lavage or throat swab/nasal swab was collected in viral transport medium for analysis of RVs by multiplex real-time polymerase chain reaction. A total of 135 cirrhotic patients were included, viral and bacterial etiology of pneumonia was identified, and analysis was done with the clinical outcome. RESULTS: Overall, RVs were detected in 30 (22.2%) cirrhotic patients and viral–bacterial coinfection in 16 (11.8%) cirrhotic patients. The most common virus detected was rhinovirus in 9 (30%) patients. Mortality in cirrhotic patients with RV infection was significantly higher in comparison to cirrhotic patients with no RV infection (25 [83.3%] and 11 [12.3%], respectively, P < 0.001). CONCLUSION: Respiratory viruses in cirrhotic patients with pneumonia are associated with poor clinical outcome.",2019 Oct-Dec,"['Bajpai, Vijeta', 'Gupta, Ekta', 'Mitra, Lalita Gauri', 'Kumar, Hemant', 'Maiwall, Rakhi', 'Soni, Kapil Dev', 'Gupta, Amit']",J Lab Physicians,,,
,PMC,Low versus high pulse oxygen saturation directed oxygen therapy in critically ill patients: a randomized controlled pilot study,http://dx.doi.org/10.21037/jtd.2019.09.66,PMC6837987,,,"BACKGROUND: Data on the safety and feasibility of pulse oxygen saturation (SpO(2)) directed oxygen therapy in mainland China are scarce. The aim of this pilot study was to test the feasibility of SpO(2) directed oxygen therapy and to calculate sample size base on differences in 28-day mortality rates for a large sample-sized randomized trial. METHODS: This prospective pilot study enrolled 214 adult patients with an expected intensive care unit (ICU) stay of more than 72 hours. Patients were randomized into a low SpO(2) group (SpO(2) 90–95%) or high SpO(2) group (SpO(2) 96–100%). The primary outcome was 28-day mortality. RESULTS: One hundred patients were included in the low SpO(2) group, and 114 patients were included in the high SpO(2) group. The demographic and baseline characteristics were not different. The time-weighted SpO(2) average was significantly lower in the low SpO(2) group than in the high SpO(2) group [mean ± standard deviation (SD), 95.7%±2.3% vs. 98.2%±1.8%, P<0.001]. Twenty-six patients (26%) in the low SpO(2) group died within 28 days after inclusion, while 37 patients (32.5%) in the high SpO(2) group died (P=0.301). The time to death within 28 days between the two groups was not different (P=0.284). CONCLUSIONS: SpO(2) directed oxygen therapy in critically ill patients was feasible. Our pilot trial necessitates and rationalizes our large-sample multicenter trial.",,"['Yang, Xiaobo', 'Shang, You', 'Yuan, Shiying']",,,,
,PMC,tailfindr: alignment-free poly(A) length measurement for Oxford Nanopore RNA and DNA sequencing,http://dx.doi.org/10.1261/rna.071332.119,PMC6800471,,,"Polyadenylation at the 3′-end is a major regulator of messenger RNA and its length is known to affect nuclear export, stability, and translation, among others. Only recently have strategies emerged that allow for genome-wide poly(A) length assessment. These methods identify genes connected to poly(A) tail measurements indirectly by short-read alignment to genetic 3′-ends. Concurrently, Oxford Nanopore Technologies (ONT) established full-length isoform-specific RNA sequencing containing the entire poly(A) tail. However, assessing poly(A) length through base-calling has so far not been possible due to the inability to resolve long homopolymeric stretches in ONT sequencing. Here we present tailfindr, an R package to estimate poly(A) tail length on ONT long-read sequencing data. tailfindr operates on unaligned, base-called data. It measures poly(A) tail length from both native RNA and DNA sequencing, which makes poly(A) tail studies by full-length cDNA approaches possible for the first time. We assess tailfindr’s performance across different poly(A) lengths, demonstrating that tailfindr is a versatile tool providing poly(A) tail estimates across a wide range of sequencing conditions.",,"['Krause, Maximilian', 'Niazi, Adnan M.', 'Labun, Kornel', 'Torres Cleuren, Yamila N.', 'Müller, Florian S.', 'Valen, Eivind']",,,,
,PMC,Structural Definition of a Neutralization-sensitive Epitope on the MERS-CoV S1-NTD,http://dx.doi.org/10.1016/j.celrep.2019.08.052,PMC6935267,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human population in 2012 and has caused substantial morbidity and mortality. Potently neutralizing antibodies targeting the receptor-binding domain (RBD) on MERS-CoV spike (S) protein have been characterized, but much less is known about antibodies targeting non-RBD epitopes. Here we report the structural and functional characterization of G2, a neutralizing antibody targeting MERS-CoV S1 N-terminal domain (S1-NTD). Structures of G2 alone and in complex with the MERS-CoV S1-NTD defined a site of vulnerability comprising two loops, each of which contained a residue mutated in G2-escape variants. Cell-surface binding studies and in vitro competition experiments demonstrated that G2 strongly disrupts the attachment of MERS-CoV S to its receptor DDP4, with the inhibition requiring the native trimeric S conformation. These results advance our understanding of antibody-mediated neutralization of coronaviruses and should facilitate development of immunotherapeutics and vaccines against MERS-CoV.",,"['Wang, Nianshuang', 'Rosen, Osnat', 'Wang, Lingshu', 'Turner, Hannah L.', 'Stevens, Laura J.', 'Corbett, Kizzmekia S.', 'Bowman, Charles A.', 'Pallesen, Jesper', 'Shi, Wei', 'Zhang, Yi', 'Leung, Kwanyee', 'Kirchdoerfer, Robert N.', 'Becker, Michelle M.', 'Denison, Mark R.', 'Chappell, James D.', 'Ward, Andrew B.', 'Graham, Barney S.', 'McLellan, Jason S.']",,,,
,PMC,Antiviral immunity is impaired in COPD patients with frequent exacerbations,http://dx.doi.org/10.1152/ajplung.00253.2019,PMC6962603,31513433,CC BY,Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) subgroup requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (≥2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the antiviral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. A role for epithelial cell-intrinsic innate immune dysregulation was identified: induction of interferons and ISGs during in vitro rhinovirus (RV) infection was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators additionally had increased sputum bacterial loads at 2 wk following virus-associated exacerbation onset. These data implicate deficient airway innate immunity involving epithelial cells in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate antimicrobial immunity in the lung could be a viable strategy for prevention and treatment of frequent exacerbations.,2019 Dec 1,"['Singanayagam, Aran', 'Loo, Su-Ling', 'Calderazzo, Maria', 'Finney, Lydia J.', 'Trujillo Torralbo, Maria-Belen', 'Bakhsoliani, Eteri', 'Girkin, Jason', 'Veerati, Punnam', 'Pathinayake, Prabuddha S.', 'Nichol, Kristy S.', 'Reid, Andrew', 'Footitt, Joseph', 'Wark, Peter A. B.', 'Grainge, Christopher L.', 'Johnston, Sebastian L.', 'Bartlett, Nathan W.', 'Mallia, Patrick']",Am J Physiol Lung Cell Mol Physiol,,,
,PMC,Many human RNA viruses show extraordinarily stringent selective constraints on protein evolution,http://dx.doi.org/10.1073/pnas.1907626116,PMC6754614,,,"How negative selection, positive selection, and population size contribute to the large variation in nucleotide substitution rates among RNA viruses remains unclear. Here, we studied the ratios of nonsynonymous-to-synonymous substitution rates (d(N)/d(S)) in protein-coding genes of human RNA and DNA viruses and mammals. Among the 21 RNA viruses studied, 18 showed a genome-average d(N)/d(S) from 0.01 to 0.10, indicating that over 90% of nonsynonymous mutations are eliminated by negative selection. Only HIV-1 showed a d(N)/d(S) (0.31) higher than that (0.22) in mammalian genes. By comparing the d(N)/d(S) values among genes in the same genome and among species or strains, we found that both positive selection and population size play significant roles in the d(N)/d(S) variation among genes and species. Indeed, even in flaviviruses and picornaviruses, which showed the lowest ratios among the 21 species studied, positive selection appears to have contributed significantly to d(N)/d(S). We found the view that positive selection occurs much more frequently in influenza A subtype H3N2 than subtype H1N1 holds only for the hemagglutinin and neuraminidase genes, but not for other genes. Moreover, we found no support for the view that vector-borne RNA viruses have lower d(N)/d(S) ratios than non–vector-borne viruses. In addition, we found a correlation between d(N) and d(S), implying a correlation between d(N) and the mutation rate. Interestingly, only 2 of the 8 DNA viruses studied showed a d(N)/d(S) < 0.10, while 4 showed a d(N)/d(S) > 0.22. These observations increase our understanding of the mechanisms of RNA virus evolution.",,"['Lin, Jinn-Jy', 'Bhattacharjee, Maloyjo Joyraj', 'Yu, Chun-Ping', 'Tseng, Yan Yuan', 'Li, Wen-Hsiung']",,,,
,PMC,N95 Respirators vs Medical Masks for Preventing Influenza Among Health Care Personnel: A Randomized Clinical Trial,http://dx.doi.org/10.1001/jama.2019.11645,PMC6724169,,,"IMPORTANCE: Clinical studies have been inconclusive about the effectiveness of N95 respirators and medical masks in preventing health care personnel (HCP) from acquiring workplace viral respiratory infections. OBJECTIVE: To compare the effect of N95 respirators vs medical masks for prevention of influenza and other viral respiratory infections among HCP. DESIGN, SETTING, AND PARTICIPANTS: A cluster randomized pragmatic effectiveness study conducted at 137 outpatient study sites at 7 US medical centers between September 2011 and May 2015, with final follow-up in June 2016. Each year for 4 years, during the 12-week period of peak viral respiratory illness, pairs of outpatient sites (clusters) within each center were matched and randomly assigned to the N95 respirator or medical mask groups. INTERVENTIONS: Overall, 1993 participants in 189 clusters were randomly assigned to wear N95 respirators (2512 HCP-seasons of observation) and 2058 in 191 clusters were randomly assigned to wear medical masks (2668 HCP-seasons) when near patients with respiratory illness. MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of laboratory-confirmed influenza. Secondary outcomes included incidence of acute respiratory illness, laboratory-detected respiratory infections, laboratory-confirmed respiratory illness, and influenzalike illness. Adherence to interventions was assessed. RESULTS: Among 2862 randomized participants (mean [SD] age, 43 [11.5] years; 2369 [82.8%]) women), 2371 completed the study and accounted for 5180 HCP-seasons. There were 207 laboratory-confirmed influenza infection events (8.2% of HCP-seasons) in the N95 respirator group and 193 (7.2% of HCP-seasons) in the medical mask group (difference, 1.0%, [95% CI, −0.5% to 2.5%]; P = .18) (adjusted odds ratio [OR], 1.18 [95% CI, 0.95-1.45]). There were 1556 acute respiratory illness events in the respirator group vs 1711 in the mask group (difference, −21.9 per 1000 HCP-seasons [95% CI, −48.2 to 4.4]; P = .10); 679 laboratory-detected respiratory infections in the respirator group vs 745 in the mask group (difference, −8.9 per 1000 HCP-seasons, [95% CI, −33.3 to 15.4]; P = .47); 371 laboratory-confirmed respiratory illness events in the respirator group vs 417 in the mask group (difference, −8.6 per 1000 HCP-seasons [95% CI, −28.2 to 10.9]; P = .39); and 128 influenzalike illness events in the respirator group vs 166 in the mask group (difference, −11.3 per 1000 HCP-seasons [95% CI, −23.8 to 1.3]; P = .08). In the respirator group, 89.4% of participants reported “always” or “sometimes” wearing their assigned devices vs 90.2% in the mask group. CONCLUSIONS AND RELEVANCE: Among outpatient health care personnel, N95 respirators vs medical masks as worn by participants in this trial resulted in no significant difference in the incidence of laboratory-confirmed influenza. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01249625",,"['Radonovich, Lewis J.', 'Simberkoff, Michael S.', 'Bessesen, Mary T.', 'Brown, Alexandria C.', 'Cummings, Derek A. T.', 'Gaydos, Charlotte A.', 'Los, Jenna G.', 'Krosche, Amanda E.', 'Gibert, Cynthia L.', 'Gorse, Geoffrey J.', 'Nyquist, Ann-Christine', 'Reich, Nicholas G.', 'Rodriguez-Barradas, Maria C.', 'Price, Connie Savor', 'Perl, Trish M.']",,,,
,PMC,Characteristics and preparation of the last-minute traveler: analysis of vaccine usage in the Global TravEpiNet Consortium,http://dx.doi.org/10.1093/jtm/taz031,PMC6736758,,,"BACKGROUND: Last-minute travellers (LMTs) present challenges for health care providers because they may have insufficient time for recommended vaccinations or pre-travel preparation. Our objective was to obtain a better understanding of LMTs in order to help travel medicine providers develop improved strategies to decrease the number of LMTs and potentially reduce travel-related morbidity. METHODS: We defined LMTs as travellers with a departure date of 7 days or fewer from the medical encounter. We analysed the characteristics and health preparation of 12 494 LMTs who presented to a network of US clinical practices for pre-travel health advice between January 2009 and December 2015. RESULTS: LMTs comprised 16% of all travellers. More LMTs than non-LMTs travelled for business or to visit friends and relatives (VFR) (26% vs 16% and 15% vs 8%, respectively; P< 0.0001). More LMTs also travelled for longer than 1 month (27% vs 21%; P<0.0001) and visited only urban areas (40% vs 29%; P<0.0001). At least one travel vaccine was deferred by 18% of LMTs because of insufficient time before departure. Vaccines that required multiple vaccinations, such as Japanese encephalitis and rabies, were the most likely to be deferred because of time constraints. CONCLUSION: Interventions to improve the timing of pre-travel health consultations should be developed, particularly for business and VFR travellers. Recently endorsed accelerated vaccine schedules for Japanese encephalitis and rabies may help some LMTs receive protection against these infections despite late presentation for pre-travel health care.",,"['Yates, Johnnie A.', 'Rao, Sowmya R.', 'Walker, Allison Taylor', 'Esposito, Douglas H.', 'Sotir, Mark', 'LaRocque, Regina C.', 'Ryan, Edward T.', None]",,,,
,PMC,Ensuring Compliance With Quarantine by Undocumented Immigrants and Other Vulnerable Groups: Public Health Versus Politics,http://dx.doi.org/10.2105/AJPH.2019.305201,PMC6687239,,,"A successful quarantine requires a high rate of compliance by individuals with potential exposure to a communicable disease. Many individuals would be reluctant to comply with a quarantine because they fear that contact with government officials will place them in legal, personal, or economic jeopardy. These include undocumented immigrants and individuals with a substance use disorder. For a quarantine to succeed, individuals must be granted temporary immunity from arrest, deportation, or similar adverse consequences, but doing so will be politically unpopular. We argue that public health considerations must take precedence over politics in protecting the health of the public.",,"['Rothstein, Mark A.', 'Coughlin, Christine N.']",,,,
,PMC,Respiratory tract mucous membrane microecology and asthma,http://dx.doi.org/10.21037/atm.2019.09.06,PMC6803190,,,"According to the world health organization, the increasing incidence of asthma is placing a heavy burden on the social economy. Its high rate of disability and mortality has become a serious social and public health problem. Asthma is a heterogeneous disease in which genetic polymorphism interacts with environmental factors. Because the pathogenesis of asthma is not completely clear, there is no specific treatment. In 2010, 16S rRNA gene sequencing showed that lungs have many different microbial communities in both healthy and sick states. These microbial communities and respiratory mucosa constitute the respiratory mucosal microecology. When the respiratory mucosal microecology changes, it can play a key role in the occurrence and development of asthma and other respiratory diseases by regulating the immune mechanism. This paper reviews the latest research results in this field, and tries to explore the effects of changes in respiratory mucosal microecology on the pathogenesis of asthma, so as to provide new methods for early diagnosis, treatment and prevention of asthma.",,"['Chen, Xingyuan', 'Qiu, Chen']",,,,
,PMC,Identification of etiologic agents and clinical characteristics for patients suspected of having pertussis in a large Children’s Hospital in China,http://dx.doi.org/10.21037/atm.2019.08.85,PMC6803182,,,"BACKGROUND: In China, pertussis is a major health problem with an increasing incidence despite immunization efforts. Timely and accurate diagnosis is essential for the optimal management of pertussis, especially in severe cases. METHODS: Nasopharyngeal swabs or sputum specimens were obtained from patients suspected of having pertussis on the day of hospitalization at Shanghai Children’s Medical Center from December 01, 2016, to November 30, 2017. The specimens were tested with the FilmArray Respiratory Panel, a multiplex polymerase chain reaction (PCR) assay that detects 16 viruses, Bordetella pertussis (B. pertussis), Mycoplasma pneumoniae (M. pneumoniae), and Chlamydophila pneumoniae (C. pneumoniae). RESULTS: Among the 140 children studied, 50.0% (70/140) were detected with a single pathogen, 45.0% (63/140) were detected with multiple pathogens, and 5.0% (7/140) had no detected pathogens. Forty-nine (35%, 49/140) patients tested positive for B. pertussis. Respiratory syncytial virus (RSV), parainfluenza virus (Para) and rhinovirus/enterovirus (Rhino/Entero) were the most prevalent pathogens in patients with pertussis-like syndrome. No significant differences between the groups with pertussis and pertussis-like syndrome were observed regarding the clinical symptoms. Severe cases were more frequently observed in unvaccinated, premature and pertussis/RSV co-infection patients. CONCLUSIONS: Our study highlights the importance of the timely and accurate diagnosis of pertussis based on both clinical symptoms and laboratory methods.",,"['Tao, Yue', 'Tang, Mingyu', 'Luo, Lijuan', 'Xiang, Long', 'Xia, Yijun', 'Li, Biru', 'Cao, Qing', 'Mo, Xi']",,,,
,PMC,Direct RNA nanopore sequencing of full-length coronavirus genomes provides novel insights into structural variants and enables modification analysis,http://dx.doi.org/10.1101/gr.247064.118,PMC6724671,,,"Sequence analyses of RNA virus genomes remain challenging owing to the exceptional genetic plasticity of these viruses. Because of high mutation and recombination rates, genome replication by viral RNA-dependent RNA polymerases leads to populations of closely related viruses, so-called “quasispecies.” Standard (short-read) sequencing technologies are ill-suited to reconstruct large numbers of full-length haplotypes of (1) RNA virus genomes and (2) subgenome-length (sg) RNAs composed of noncontiguous genome regions. Here, we used a full-length, direct RNA sequencing (DRS) approach based on nanopores to characterize viral RNAs produced in cells infected with a human coronavirus. By using DRS, we were able to map the longest (∼26-kb) contiguous read to the viral reference genome. By combining Illumina and Oxford Nanopore sequencing, we reconstructed a highly accurate consensus sequence of the human coronavirus (HCoV)-229E genome (27.3 kb). Furthermore, by using long reads that did not require an assembly step, we were able to identify, in infected cells, diverse and novel HCoV-229E sg RNAs that remain to be characterized. Also, the DRS approach, which circumvents reverse transcription and amplification of RNA, allowed us to detect methylation sites in viral RNAs. Our work paves the way for haplotype-based analyses of viral quasispecies by showing the feasibility of intra-sample haplotype separation. Even though several technical challenges remain to be addressed to exploit the potential of the nanopore technology fully, our work illustrates that DRS may significantly advance genomic studies of complex virus populations, including predictions on long-range interactions in individual full-length viral RNA haplotypes.",,"['Viehweger, Adrian', 'Krautwurst, Sebastian', 'Lamkiewicz, Kevin', 'Madhugiri, Ramakanth', 'Ziebuhr, John', 'Hölzer, Martin', 'Marz, Manja']",,,,
,PMC,Lack of Absorption of a Sustained-release Buprenorphine Formulation Administered Subcutaneously to Athymic Nude Rats,http://dx.doi.org/10.30802/AALAS-JAALAS-19-000013,PMC6774464,,,"Female athymic nude rats (Rattus norvegicus; n = 45; age, 6 wk) were used in an IACUC-approved protocol to investigate mechanisms and potential treatments associated with brain, spine, and spinal cord metastases from triple negative breast cancer. The analgesic plan included the use of buprenorphine SR LAB (0.6 mg/kg; 0.11 mL/rat) subcutaneously and an oral NSAID delivered via the water. Thirty-seven rats reached the experimental end point at 3 mo after xenotransplantation and were euthanized for tissue harvest. Grossly, all 37 rats had nodules in the subcutis over the shoulders; these were identified as small, cystic structures (diameter, approximately 0.25 cm). The cysts and haired skin were submitted for LC-MS/MS (liquid chromatography-tandem mass spectrometry) and histopathology. Histologically, the cysts were lined by fibrous connective tissue mildly infiltrated by macrophages, lymphocytes, and plasma cells. Adjacent blood vessels were rimmed by a mild infiltrate of lymphocytes and plasma cells. The cysts contained variable accumulations of a light pink, proteinaceous fluid. The cause for the cysts could not be determined histologically; there was no evidence of neoplasia. LC-MS/MS analysis revealed that the cysts contained buprenorphine. We hypothesize that the lack of T cells and a cell-mediated immune response in these rats prevented the dissolution of the vehicle and absorption of the buprenorphine. The manufacturer provides a cautionary statement regarding the use of this formulation in nude mice due to skin reactions, but to our knowledge, this report is the first description of an apparent lack of absorption of the drug in immunodeficient animals.",,"['Page, C Douglas', 'Sarabia-Estrada, Rachel', 'Hoffman, R Jay', 'Lo, Chih-Ping', 'Gades, Naomi M']",,,,
,PMC,"Abstracts of Scientific Presentations 2019 AALAS National Meeting Denver, Colorado",,PMC6774462,,,,,,,,,
,PMC,Estimation of the actual disease burden of human H7N9 infection in Jiangsu of eastern China from March 2013 to September 2017,http://dx.doi.org/10.7555/JBR.33.20180127,PMC6813534,,,"The actual incidence of human H7N9 infection is supposed to be much higher than the documented laboratory-confirmed cases. In this study, we estimated the number of the actual H7N9 cases in Jiangsu, China using a probabilistic multiplier model. Then, disability adjusted life years (DALYs), direct and indirect economic loss caused by this disease were calculated and analyzed. Till September 2017, the estimated total number of H7N9 cases was 2 952 [median, 90% probability range (PR): 1 487−22 094], which was 11.8 times (5.9−88.4) as large as the reported number. The median morbidity was estimated to be 4 (90% PR: 2−29) per 100 000 population. The total DALYs loss was 16 548 years, and the total economic loss (direct and indirect) was estimated to be RMB 1 044 618 758 (US$ 16.7 M). The average economic loss for per case and for per year was RMB 353 868 (US$ 56 440) and RMB 232 137 502 (US$ 37.0 M), respectively. The actual burden of human H7N9 infections was much heavier than what was documented. Our study provided an approach to estimate actual burden of infectious diseases using laboratory-confirmation.",,"['Huang, Haodi', 'Ma, Wang', 'Xu, Ke', 'Dear, Keith', 'Yu, Huiyan', 'Qi, Xian', 'Bao, Changjun', 'Zhou, Minghao', 'Huo, Xiang']",,,,
,PMC,"Community's compliance with measures for the prevention of respiratory infections in Riyadh, Saudi Arabia",http://dx.doi.org/10.4103/jfcm.JFCM_4_19,PMC6755768,31572047,CC BY-NC-SA,"BACKGROUND: Acute respiratory tract infections are the most common causes of both morbidity and mortality worldwid, and the management and prevention of acute respiratory infections is a global problem, especially in developing countries. This study sought to assess the community's compliance and practice of measures for the prevention of respiratory infections and discover their source of health information. MATERIALS AND METHODS: A cross-sectional study was carried out in the five biggest shopping malls in Riyadh city in July 2014. The required sample size was 980 persons aged 15 or older, with 196 from each of the five biggest shopping malls from each of the five geographic areas of Riyadh. Data was collected by face-to-face interview using standardised questionnaire, and analyzed using SPSS. RESULTS: Overall, 48.3% of the participants thought that they were susceptible to any of the respiratory infections of pandemic influenza; 59.7% always washed their hands with water and soap and 34.8% used antibacterial soap. About 29% reported avoiding touching their eyes, noses, and mouths directly with their hands; 63.5% covered their noses and mouths with tissue paper when sneezing or coughing. A substantial number said they “never” shared their personal stuff, including towels (70.5%) and utensils (49.0%) with others. Only 21.2% avoided crowded places or wore a mask (9.1%) in such a situation. A high proportion (62.8%) did not take the seasonal flu vaccine. The most common sources of health information included television/radio (47.9%), social media (29.4%), and friends/family (28.1%). CONCLUSIONS: Health authorities should seize every opportunity to prevent respiratory infections by adopting all evidence-based infection control measures to improve public awareness, attitude, and practice.",2019 Sep-Dec,"['Alhazmi, Ali M.', 'Alshammari, Sulaiman A.', 'Alenazi, Hanan A.', 'Shaik, Shaffi A.', 'AlZaid, Hala M.', 'Almahmoud, Nouf S.', 'Alshammari, Hotoon S.']",J Family Community Med,,,
,PMC,"China in transition: health, wealth, and globalisation",http://dx.doi.org/10.1016/S2468-2667(19)30151-3,PMC6790332,,,,,"['Liu, Gordon G', 'Chen, Xi']",,,,
,PMC,A Zoonotic Adenoviral Human Pathogen Emerged through Genomic Recombination among Human and Nonhuman Simian Hosts,http://dx.doi.org/10.1128/JVI.00564-19,PMC6714811,,,"Genomics analysis of a historically intriguing and predicted emergent human adenovirus (HAdV) pathogen, which caused pneumonia and death, provides insight into a novel molecular evolution pathway involving “ping-pong” zoonosis and anthroponosis. The genome of this promiscuous pathogen is embedded with evidence of unprecedented multiple, multidirectional, stable, and reciprocal cross-species infections of hosts from three species (human, chimpanzee, and bonobo). This recombinant genome, typed as HAdV-B76, is identical to two recently reported simian AdV (SAdV) genomes isolated from chimpanzees and bonobos. Additionally, the presence of a critical adenoviral replication element found in HAdV genomes, in addition to genes that are highly similar to counterparts in other HAdVs, reinforces its potential as a human pathogen. Reservoirs in nonhuman hosts may explain periods of apparent absence and then reemergence of human adenoviral pathogens, as well as present pathways for the genesis of those thought to be newly emergent. The nature of the HAdV-D76 genome has implications for the use of SAdVs as gene delivery vectors in human gene therapy and vaccines, selected to avoid preexisting and potentially fatal host immune responses to HAdV. IMPORTANCE An emergent adenoviral human pathogen, HAdV-B76, associated with a fatality in 1965, shows a remarkable degree of genome identity with two recently isolated simian adenoviruses that contain cross-species genome recombination events from three hosts: human, chimpanzee, and bonobo. Zoonosis (nonhuman-to-human transmission) and anthroponosis (human to nonhuman transmission) may play significant roles in the emergence of human adenoviral pathogens.",,"['Dehghan, Shoaleh', 'Seto, Jason', 'Liu, Elizabeth B.', 'Ismail, Ashrafali M.', 'Madupu, Ramana', 'Heim, Albert', 'Jones, Morris S.', 'Dyer, David W.', 'Chodosh, James', 'Seto, Donald']",,,,
,PMC,Adaptive Mutations in Replicase Transmembrane Subunits Can Counteract Inhibition of Equine Arteritis Virus RNA Synthesis by Cyclophilin Inhibitors,http://dx.doi.org/10.1128/JVI.00490-19,PMC6714810,,,"Previously, the cyclophilin inhibitors cyclosporine (CsA) and alisporivir (ALV) were shown to inhibit the replication of diverse RNA viruses, including arteriviruses and coronaviruses, which both belong to the order Nidovirales. In this study, we aimed to identify arterivirus proteins involved in the mode of action of cyclophilin inhibitors and to investigate how these compounds inhibit arterivirus RNA synthesis in the infected cell. Repeated passaging of the arterivirus prototype equine arteritis virus (EAV) in the presence of CsA revealed that reduced drug sensitivity is associated with the emergence of adaptive mutations in nonstructural protein 5 (nsp5), one of the transmembrane subunits of the arterivirus replicase polyprotein. Introduction of singular nsp5 mutations (nsp5 Q21R, Y113H, or A134V) led to an ∼2-fold decrease in sensitivity to CsA treatment, whereas combinations of mutations further increased EAV’s CsA resistance. The detailed experimental characterization of engineered EAV mutants harboring CsA resistance mutations implicated nsp5 in arterivirus RNA synthesis. Particularly, in an in vitro assay, EAV RNA synthesis was far less sensitive to CsA treatment when nsp5 contained the adaptive mutations mentioned above. Interestingly, for increased sensitivity to the closely related drug ALV, CsA-resistant nsp5 mutants required the incorporation of an additional adaptive mutation, which resided in nsp2 (H114R), another transmembrane subunit of the arterivirus replicase. Our study provides the first evidence for the involvement of nsp2 and nsp5 in the mechanism underlying the inhibition of arterivirus replication by cyclophilin inhibitors. IMPORTANCE Currently, no approved treatments are available to combat infections with nidoviruses, a group of positive-stranded RNA viruses, including important zoonotic and veterinary pathogens. Previously, the cyclophilin inhibitors cyclosporine (CsA) and alisporivir (ALV) were shown to inhibit the replication of diverse nidoviruses (both arteriviruses and coronaviruses), and they may thus represent a class of pan-nidovirus inhibitors. In this study, using the arterivirus prototype equine arteritis virus, we have established that resistance to CsA and ALV treatment is associated with adaptive mutations in two transmembrane subunits of the viral replication machinery, nonstructural proteins 2 and 5. This is the first evidence for the involvement of specific replicase subunits of arteriviruses in the mechanism underlying the inhibition of their replication by cyclophilin inhibitors. Understanding this mechanism of action is of major importance to guide future drug design, both for nidoviruses and for other RNA viruses inhibited by these compounds.",,"['de Wilde, Adriaan H.', 'Boomaars-van der Zanden, A. Linda', 'de Jong, Anja W. M.', 'Bárcena, Montserrat', 'Snijder, Eric J.', 'Posthuma, Clara C.']",,,,
,PMC,Disrupted CXCR2 Signaling in Oligodendroglia Lineage Cells Enhances Myelin Repair in a Viral Model of Multiple Sclerosis,http://dx.doi.org/10.1128/JVI.00240-19,PMC6714798,,,"CXCR2 is a chemokine receptor expressed on oligodendroglia that has been implicated in the pathogenesis of neuroinflammatory demyelinating diseases as well as enhancement of the migration, proliferation, and myelin production by oligodendroglia. Using an inducible proteolipid protein (Plp) promoter-driven Cre-loxP recombination system, we were able to assess how timed ablation of Cxcr2 in oligodendroglia affected disease following intracranial infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV). Generation of Plp-Cre-ER(T)::Cxcr2(flox/flox) transgenic mice (termed Cxcr2-CKO mice) allows for Cxcr2 to be silenced in oligodendrocytes in adult mice following treatment with tamoxifen. Ablation of oligodendroglia Cxcr2 did not influence clinical severity in response to intracranial infection with JHMV. Infiltration of activated T cells or myeloid cells into the central nervous system (CNS) was not affected, nor was the ability to control viral infection. In addition, the severity of demyelination was similar between tamoxifen-treated mice and vehicle-treated controls. Notably, deletion of Cxcr2 resulted in increased remyelination, as assessed by g-ratio (the ratio of the inner axonal diameter to the total outer fiber diameter) calculation, compared to that in vehicle-treated control mice. Collectively, our findings argue that CXCR2 signaling in oligodendroglia is dispensable with regard to contributing to neuroinflammation, but its deletion enhances remyelination in a preclinical model of the human demyelinating disease multiple sclerosis (MS). IMPORTANCE Signaling through the chemokine receptor CXCR2 in oligodendroglia is important for developmental myelination in rodents, while chemical inhibition or nonspecific genetic deletion of CXCR2 appears to augment myelin repair in animal models of the human demyelinating disease multiple sclerosis (MS). To better understand the biology of CXCR2 signaling on oligodendroglia, we generated transgenic mice in which Cxcr2 is selectively ablated in oligodendroglia upon treatment with tamoxifen. Using a viral model of neuroinflammation and demyelination, we demonstrate that genetic silencing of CXCR2 on oligodendroglia did not affect clinical disease, neuroinflammation, or demyelination, yet there was increased remyelination. These findings support and extend previous findings suggesting that targeting CXCR2 may offer a therapeutic avenue for enhancing remyelination in patients with demyelinating diseases.",,"['Marro, Brett S.', 'Skinner, Dominic D.', 'Cheng, Yuting', 'Grist, Jonathan J.', 'Dickey, Laura L.', 'Eckman, Emily', 'Stone, Colleen', 'Liu, Liping', 'Ransohoff, Richard M.', 'Lane, Thomas E.']",,,,
,PMC,Newcastle Disease Virus V Protein Degrades Mitochondrial Antiviral Signaling Protein To Inhibit Host Type I Interferon Production via E3 Ubiquitin Ligase RNF5,http://dx.doi.org/10.1128/JVI.00322-19,PMC6714796,,,"Paramyxovirus establishes an intimate and complex interaction with the host cell to counteract the antiviral responses elicited by the cell. Of the various pattern recognition receptors in the host, the cytosolic RNA helicases interact with viral RNA to activate the mitochondrial antiviral signaling protein (MAVS) and subsequent cellular interferon (IFN) response. On the other hand, viruses explore multiple strategies to resist host immunity. In this study, we found that Newcastle disease virus (NDV) infection induced MAVS degradation. Further analysis showed that NDV V protein degraded MAVS through the ubiquitin-proteasome pathway to inhibit IFN-β production. Moreover, NDV V protein led to proteasomal degradation of MAVS through Lys362 and Lys461 ubiquitin to prevent IFN production. Further studies showed that NDV V protein recruited E3 ubiquitin ligase RNF5 to polyubiquitinate and degrade MAVS. Compared with levels for wild-type NDV infection, V-deficient NDV induced attenuated MAVS degradation and enhanced IFN-β production at the late stage of infection. Several other paramyxovirus V proteins showed activities of degrading MAVS and blocking IFN production similar to those of NDV V protein. The present study revealed a novel role of NDV V protein in targeting MAVS to inhibit cellular IFN production, which reinforces the fact that the virus orchestrates the cellular antiviral response to its own benefit. IMPORTANCE Host anti-RNA virus innate immunity relies mainly on the recognition by retinoic acid-inducible gene I and melanoma differentiation-associated protein 5 and subsequently initiates downstream signaling through interaction with MAVS. On the other hand, viruses have developed various strategies to counteract MAVS-mediated signaling. The mechanism for paramyxoviruses regulating MAVS to benefit their infection remains unknown. In this article, we demonstrate that the V proteins of NDV and several other paramyxoviruses target MAVS for ubiquitin-mediated degradation through E3 ubiquitin ligase RING-finger protein 5 (RNF5). MAVS degradation leads to the inhibition of the downstream IFN-β pathway and therefore benefits virus proliferation. Our study reveals a novel mechanism of NDV evading host innate immunity and provides insight into the therapeutic strategies for the control of paramyxovirus infection.",,"['Sun, Yingjie', 'Zheng, Hang', 'Yu, Shengqing', 'Ding, Yunlei', 'Wu, Wei', 'Mao, Xuming', 'Liao, Ying', 'Meng, Chunchun', 'Ur Rehman, Zaib', 'Tan, Lei', 'Song, Cuiping', 'Qiu, Xusheng', 'Wu, Fengyun', 'Ding, Chan']",,,,
,PMC,FEZ1 Is Recruited to a Conserved Cofactor Site on Capsid to Promote HIV-1 Trafficking,http://dx.doi.org/10.1016/j.celrep.2019.07.079,PMC6736649,,,"HIV-1 uses the microtubule network to traffic the viral capsid core toward the nucleus. Viral nuclear trafficking and infectivity require the kinesin-1 adaptor protein FEZ1. Here, we demonstrate that FEZ1 directly interacts with the HIV-1 capsid and specifically binds capsid protein (CA) hexamers. FEZ1 contains multiple acidic, poly-glutamate stretches that interact with the positively charged central pore of CA hexamers. The FEZ1-capsid interaction directly competes with nucleotides and inositol hexaphosphate (IP6) that bind at the same location. In addition, all-atom molecular dynamic (MD) simulations establish the molecular details of FEZ1-capsid interactions. Functionally, mutation of the FEZ1 capsid-interacting residues significantly reduces trafficking of HIV-1 particles toward the nucleus and early infection. These findings support a model in which the central capsid hexamer pore is a general HIV-1 cofactor-binding hub and FEZ1 serves as a unique CA hexamer pattern sensor to recognize this site and promote capsid trafficking in the cell.",,"['Huang, Pei-Tzu', 'Summers, Brady James', 'Xu, Chaoyi', 'Perilla, Juan R.', 'Malikov, Viacheslav', 'Naghavi, Mojgan H.', 'Xiong, Yong']",,,,
,PMC,A Hydrophobic Target: Using the Paramyxovirus Fusion Protein Transmembrane Domain To Modulate Fusion Protein Stability,http://dx.doi.org/10.1128/JVI.00863-19,PMC6694835,,,"Enveloped viruses utilize surface glycoproteins to bind and fuse with a target cell membrane. The zoonotic Hendra virus (HeV), a member of the family Paramyxoviridae, utilizes the attachment protein (G) and the fusion protein (F) to perform these critical functions. Upon triggering, the trimeric F protein undergoes a large, irreversible conformation change to drive membrane fusion. Previously, we have shown that the transmembrane (TM) domain of the F protein, separate from the rest of the protein, is present in a monomer-trimer equilibrium. This TM-TM association contributes to the stability of the prefusion form of the protein, supporting a role for TM-TM interactions in the control of F protein conformational changes. To determine the impact of disrupting TM-TM interactions, constructs expressing the HeV F TM with limited flanking sequences were synthesized. Coexpression of these constructs with HeV F resulted in dramatic reductions in the stability of F protein expression and fusion activity. In contrast, no effects were observed when the HeV F TM constructs were coexpressed with the nonhomologous parainfluenza virus 5 (PIV5) fusion protein, indicating a requirement for specific interactions. To further examine this, a TM peptide homologous to the PIV5 F TM domain was synthesized. Addition of the peptide prior to infection inhibited infection with PIV5 but did not significantly affect infection with human metapneumovirus, a related virus. These results indicate that targeted disruption of TM-TM interactions significantly impact viral fusion protein stability and function, presenting these interactions as a novel target for antiviral development. IMPORTANCE Enveloped viruses require virus-cell membrane fusion to release the viral genome and replicate. The viral fusion protein triggers from the pre- to the postfusion conformation, an essentially irreversible change, to drive membrane fusion. We found that small proteins containing the TM and a limited flanking region homologous to the fusion protein of the zoonotic Hendra virus reduced protein expression and fusion activity. The introduction of exogenous TM peptides may displace a TM domain, disrupting native TM-TM interactions and globally destabilizing the fusion protein. Supporting this hypothesis, we showed that a sequence-specific transmembrane peptide dramatically reduced viral infection in another enveloped virus model, suggesting a broader inhibitory mechanism. Viral fusion protein TM-TM interactions are important for protein function, and disruption of these interactions dramatically reduces protein stability.",,"['Barrett, Chelsea T.', 'Webb, Stacy R.', 'Dutch, Rebecca Ellis']",,,,
,PMC,Complex dynamics under tension in a high-efficiency frameshift stimulatory structure,http://dx.doi.org/10.1073/pnas.1905258116,PMC6765238,,,"Specific structures in mRNA can stimulate programmed ribosomal frameshifting (PRF). PRF efficiency can vary enormously between different stimulatory structures, but the features that lead to efficient PRF stimulation remain uncertain. To address this question, we studied the structural dynamics of the frameshift signal from West Nile virus (WNV), which stimulates −1 PRF at very high levels and has been proposed to form several different structures, including mutually incompatible pseudoknots and a double hairpin. Using optical tweezers to apply tension to single mRNA molecules, mimicking the tension applied by the ribosome during PRF, we found that the WNV frameshift signal formed an unusually large number of different metastable structures, including all of those previously proposed. From force-extension curve measurements, we mapped 2 mutually exclusive pathways for the folding, each encompassing multiple intermediates. We identified the intermediates in each pathway from length changes and the effects of antisense oligomers blocking formation of specific contacts. Intriguingly, the number of transitions between the different conformers of the WNV frameshift signal was maximal in the range of forces applied by the ribosome during −1 PRF. Furthermore, the occupancy of the pseudoknotted conformations was far too low for static pseudoknots to account for the high levels of −1 PRF. These results support the hypothesis that conformational heterogeneity plays a key role in frameshifting and suggest that transitions between different conformers under tension are linked to efficient PRF stimulation.",,"['Halma, Matthew T. J.', 'Ritchie, Dustin B.', 'Cappellano, Tonia R.', 'Neupane, Krishna', 'Woodside, Michael T.']",,,,
,PMC,Alternative promoters drive human cytomegalovirus reactivation from latency,http://dx.doi.org/10.1073/pnas.1900783116,PMC6717278,,,"Reactivation from latency requires reinitiation of viral gene expression and culminates in the production of infectious progeny. The major immediate early promoter (MIEP) of human cytomegalovirus (HCMV) drives the expression of crucial lytic cycle transactivators but is silenced during latency in hematopoietic progenitor cells (HPCs). Because the MIEP has poor activity in HPCs, it is unclear how viral transactivators are expressed during reactivation. It has been presumed that viral gene expression is reinitiated via de-repression of the MIEP. We demonstrate that immediate early transcripts arising from reactivation originate predominantly from alternative promoters within the canonical major immediate early locus. Disruption of these intronic promoters results in striking defects in re-expression of viral genes and viral genome replication in the THP-1 latency model. Furthermore, we show that these promoters are necessary for efficient reactivation in primary CD34(+) HPCs. Our findings shift the paradigm for HCMV reactivation by demonstrating that promoter switching governs reactivation from viral latency in a context-specific manner.",,"['Collins-McMillen, Donna', 'Rak, Mike', 'Buehler, Jason C.', 'Igarashi-Hayes, Suzu', 'Kamil, Jeremy P.', 'Moorman, Nathaniel J.', 'Goodrum, Felicia']",,,,
,PMC,Dynamic and integrative approaches to understanding pathogen spillover,http://dx.doi.org/10.1098/rstb.2019.0014,PMC6711302,,,,,"['Becker, Daniel J.', 'Washburne, Alex D.', 'Faust, Christina L.', 'Pulliam, Juliet R. C.', 'Mordecai, Erin A.', 'Lloyd-Smith, James O.', 'Plowright, Raina K.']",,,,
,PMC,Comprehensive viromewide antibody responses by systematic epitope scanning after hematopoietic cell transplantation,http://dx.doi.org/10.1182/blood.2019897405,PMC6688428,,,"Further insight into humoral viral immunity after hematopoietic cell transplantation (HCT) could have potential impact on donor selection or monitoring of patients. Currently, estimation of humoral immune recovery is inferred from lymphocyte counts or immunoglobulin levels and does not address vulnerability to specific viral infections. We interrogated the viral antibody repertoire before and after HCT using a novel serosurvey (VirScan) that detects immunoglobulin G responses to 206 viruses. We performed VirScan on cryopreserved serum from pre-HCT and 30, 100, and 365 days after myeloablative HCT from 37 donor-recipient pairs. We applied ecologic metrics (α- and β-diversity) and evaluated predictors of metrics and changes over time. Donor age and donor/recipient cytomegalovirus (CMV) serostatus and receipt systemic glucocorticoids were most strongly associated with VirScan metrics at day 100. Other clinical characteristics, including pre-HCT treatment and conditioning, did not affect antiviral repertoire metrics. The recipient repertoire was most similar (pairwise β-diversity) to that of donor at day 100, but more similar to pre-HCT self by day 365. Gain or loss of epitopes to common viruses over the year post-HCT differed by donor and recipient pre-HCT serostatus, with highest gains in naive donors to seropositive recipients for several human herpesviruses and adenoviruses. We used VirScan to highlight contributions of donor and recipient to antiviral humoral immunity and evaluate longitudinal changes. This work builds a foundation to test whether such systematic profiling could serve as a biomarker of immune reconstitution, predict clinical events after HCT, or help refine selection of optimal donors.",,"['Bender Ignacio, Rachel A.', 'Dasgupta, Sayan', 'Stevens-Ayers, Terry', 'Kula, Tomasz', 'Hill, Joshua A.', 'Lee, Stephanie J.', 'Mielcarek, Marco', 'Duerr, Ann', 'Elledge, Stephen J.', 'Boeckh, Michael']",,,,
,PMC,How exclusion from the WHO is affecting health care in Taiwan,http://dx.doi.org/10.1503/cmaj.109-5778,PMC6682475,,,,,"Shuchman, Miriam",,,,
,PMC,Effects of Corynebacterium bovis on Engraftment of Patient-derived Chronic Myelomonocytic Leukemia Cells in NSGS Mice,http://dx.doi.org/10.30802/AALAS-CM-18-000138,PMC6733163,,,"Modeling chronic myelomonocytic leukemia (CMML) in immunodeficient NSGS mice relies on unique human CMML specimens and consistent murine engraftment. Only anecdotal comments have thus far supported the notion that research data may be altered by Corynebacterium bovis, an opportunistic cutaneous pathogen of immunodeficient mice. C. bovis disseminated by asymptomatic and clinically affected mice with hyperkeratotic dermatitis, resulting in resilient facility contamination and infectious recurrence. Herein we report that, compared with C. bovis PCR-negative counterparts, C. bovis PCR-positive NSGS mice developed periocular and facial hyperkeratosis and alopecia and had reduced metrics indicative of ineffective human CMML engraftment, including less thrombocytopenia, less splenomegaly, fewer CMML infiltrates in histopathologic sections of murine organs, and fewer human CD45(+) cells in samples from murine spleen, bone marrow, and peripheral blood that were analyzed by flow cytometry. All CMML model metrics of engraftment were significantly reduced in the C. bovis PCR-positive cohort compared with the -negative cohort. In addition, a survey of comprehensive cancer center practices revealed that most murine facilities do not routinely test for C. bovis or broadly decontaminate the facility or its equipment after a C. bovis outbreak, thus increasing the likelihood of recurrence of invalidated studies. Our findings document that CMML engraftment of NSGS mice is diminished—and the integrity of murine research data jeopardized—by C. bovis infection of immunodeficient mice. In addition, our results indicate that C. bovis should be excluded from and not tolerated in murine facilities housing immunodeficient strains.",,"['Vedder, Alexis R', 'Miedel, Emily L', 'Ragland, Natalie H', 'Balasis, Maria E', 'Letson, Christopher T', 'Engelman, Robert W', 'Padron, Eric']",,,,
,PMC,How the gut microbiome regulates host immune responses to viral vaccines,http://dx.doi.org/10.1016/j.coviro.2019.05.001,PMC6863389,31163292,CC BY,"The co-evolution of the microbiota and immune system has forged a mutually beneficial relationship. This relationship allows the host to maintain the balance between active immunity to pathogens and vaccines and tolerance to self-antigens and food antigens. In children living in low-income and middle-income countries, undernourishment and repetitive gastrointestinal infections are associated with the failure of oral vaccines. Intestinal dysbiosis associated with these environmental influences, as well as some host-related factors, compromises immune responses and negatively impacts vaccine efficacy. To understand how immune responses to viral vaccines can be optimally modulated, mechanistic studies of the relationship between the microbiome, host genetics, viral infections and the development and function of the immune system are needed. We discuss the potential role of the microbiome in modulating vaccine responses in the context of a growing understanding of the relationship between the gastrointestinal microbiota, host related factors (including histo-blood group antigens) and resident immune cell populations.",2019 Aug,"['Vlasova, Anastasia N', 'Takanashi, Sayaka', 'Miyazaki, Ayako', 'Rajashekara, Gireesh', 'Saif, Linda J']",Curr Opin Virol,,,
,PMC,Neurobiological commonalities and distinctions among 3 major psychiatric disorders: a graph theoretical analysis of the structural connectome,http://dx.doi.org/10.1503/jpn.180162,PMC6919917,,,"BACKGROUND: White matter network alterations have increasingly been implicated in major depressive disorder, bipolar disorder and schizophrenia. The aim of this study was to identify shared and distinct white matter network alterations among the 3 disorders. METHODS: We used analysis of covariance, with age and gender as covariates, to investigate white matter network alterations in 123 patients with schizophrenia, 123 with bipolar disorder, 124 with major depressive disorder and 209 healthy controls. RESULTS: We found significant group differences in global network efficiency (F = 3.386, p = 0.018), nodal efficiency (F = 8.015, p < 0.001 corrected for false discovery rate [FDR]) and nodal degree (F = 5.971, p(FDR) < 0.001) in the left middle occipital gyrus, as well as nodal efficiency (F = 6.930, p(FDR) < 0.001) and nodal degree (F = 5.884, p(FDR) < 0.001) in the left postcentral gyrus. We found no significant alterations in patients with major depressive disorder. Post hoc analyses revealed that compared with healthy controls, patients in the schizophrenia and bipolar disorder groups showed decreased global network efficiency, nodal efficiency and nodal degree in the left middle occipital gyrus. Furthermore, patients in the schizophrenia group showed decreased nodal efficiency and nodal degree in the left postcentral gyrus compared with healthy controls. LIMITATIONS: Our findings could have been confounded in part by treatment differences. CONCLUSION: Our findings implicate graded white matter network alterations across the 3 disorders, enhancing our understanding of shared and distinct pathophysiological mechanisms across diagnoses and providing vital insights into neuroimaging-based methods for diagnosis and research.",,"['Wang, Shuai', 'Gong, Gaolang', 'Zhong, Suyu', 'Duan, Jia', 'Yin, Zhiyang', 'Chang, Miao', 'Wei, Shengnan', 'Jiang, Xiaowei', 'Zhou, Yifang', 'Tang, Yanqing', 'Wang, Fei']",,,,
,PMC,Highly diversified shrew hepatitis B viruses corroborate ancient origins and divergent infection patterns of mammalian hepadnaviruses,http://dx.doi.org/10.1073/pnas.1908072116,PMC6708359,,,"Shrews, insectivorous small mammals, pertain to an ancient mammalian order. We screened 693 European and African shrews for hepatitis B virus (HBV) homologs to elucidate the enigmatic genealogy of HBV. Shrews host HBVs at low prevalence (2.5%) across a broad geographic and host range. The phylogenetically divergent shrew HBVs comprise separate species termed crowned shrew HBV (CSHBV) and musk shrew HBV (MSHBV), each containing distinct genotypes. Recombination events across host orders, evolutionary reconstructions, and antigenic divergence of shrew HBVs corroborated ancient origins of mammalian HBVs dating back about 80 million years. Resurrected CSHBV replicated in human hepatoma cells, but human- and tupaia-derived primary hepatocytes were resistant to hepatitis D viruses pseudotyped with CSHBV surface proteins. Functional characterization of the shrew sodium taurocholate cotransporting polypeptide (Ntcp), CSHBV/MSHBV surface peptide binding patterns, and infection experiments revealed lack of Ntcp-mediated entry of shrew HBV. Contrastingly, HBV entry was enabled by the shrew Ntcp. Shrew HBVs universally showed mutations in their genomic preCore domains impeding hepatitis B e antigen (HBeAg) production and resembling those observed in HBeAg-negative human HBV. Deep sequencing and in situ hybridization suggest that HBeAg-negative shrew HBVs cause intense hepatotropic monoinfections and low within-host genomic heterogeneity. Geographical clustering and low MSHBV/CSHBV-specific seroprevalence suggest focal transmission and high virulence of shrew HBVs. HBeAg negativity is thus an ancient HBV infection pattern, whereas Ntcp usage for entry is not evolutionarily conserved. Shrew infection models relying on CSHBV/MSHBV revertants and human HBV will allow comparative assessments of HBeAg-mediated HBV pathogenesis, entry, and species barriers.",,"['Rasche, Andrea', 'Lehmann, Felix', 'König, Alexander', 'Goldmann, Nora', 'Corman, Victor M.', 'Moreira-Soto, Andres', 'Geipel, Andreas', 'van Riel, Debby', 'Vakulenko, Yulia A.', 'Sander, Anna-Lena', 'Niekamp, Hauke', 'Kepper, Ramona', 'Schlegel, Mathias', 'Akoua-Koffi, Chantal', 'Souza, Breno F. C. D.', 'Sahr, Foday', 'Olayemi, Ayodeji', 'Schulze, Vanessa', 'Petraityte-Burneikiene, Rasa', 'Kazaks, Andris', 'Lowjaga, Kira A. A. T.', 'Geyer, Joachim', 'Kuiken, Thijs', 'Drosten, Christian', 'Lukashev, Alexander N.', 'Fichet-Calvet, Elisabeth', 'Ulrich, Rainer G.', 'Glebe, Dieter', 'Drexler, Jan Felix']",,,,
,PMC,The androgen receptor regulates a druggable translational regulon in advanced prostate cancer,http://dx.doi.org/10.1126/scitranslmed.aaw4993,PMC6746573,,,"The androgen receptor (AR) is a driver of cellular differentiation and prostate cancer development. An extensive body of work has linked these normal and aberrant cellular processes to mRNA transcription, however, the extent to which AR regulates post-transcriptional gene regulation remains unknown. Here, we demonstrate that AR uses the translation machinery to shape the cellular proteome. We show that AR is a negative regulator of protein synthesis and identify an unexpected relationship between AR and the process of translation initiation in vivo. This is mediated through direct transcriptional control of the translation inhibitor 4EBP1. We demonstrate that lowering AR abundance increases the assembly of the eIF4F translation initiation complex, which drives enhanced tumor cell proliferation. Furthermore, we uncover a network of pro-proliferation mRNAs characterized by a guanine-rich cis-regulatory element that is particularly sensitive to eIF4F hyperactivity. Using both genetic and pharmacologic methods, we demonstrate that dissociation of the eIF4F complex reverses the proliferation program, resulting in decreased tumor growth and improved survival in preclinical models. Our findings reveal a druggable nexus that functionally links the processes of mRNA transcription and translation initiation in an emerging class of lethal AR-deficient prostate cancer.",,"['Liu, Yuzhen', 'Horn, Jessie L.', 'Banda, Kalyan', 'Goodman, Asha Z.', 'Lim, Yiting', 'Jana, Sujata', 'Arora, Sonali', 'Germanos, Alexandre A.', 'Wen, Lexiaochuan', 'Hardin, William R.', 'Yang, Yu C.', 'Coleman, Ilsa M.', 'Tharakan, Robin G.', 'Cai, Elise Y.', 'Uo, Takuma', 'Pillai, Smitha P.S.', 'Corey, Eva', 'Morrissey, Colm', 'Chen, Yu', 'Carver, Brett S.', 'Plymate, Stephen R.', 'Beronja, Slobodan', 'Nelson, Peter S.', 'Hsieh, Andrew C.']",,,,
,PMC,Zika Virus Production Is Resistant to RNase L Antiviral Activity,http://dx.doi.org/10.1128/JVI.00313-19,PMC6675901,,,"There is currently no knowledge of how the emerging human pathogen Zika virus (ZIKV) interacts with the antiviral endoribonuclease L (RNase L) pathway during infection. Since activation of RNase L during infection typically limits virus production dramatically, we used CRISPR-Cas9 gene editing technology to knockout (KO) targeted host genes involved in the RNase L pathway to evaluate the effects of RNase L on ZIKV infection in human A549 cells. RNase L was activated in response to ZIKV infection, which degraded ZIKV genomic RNA. Surprisingly, despite viral genome reduction, RNase L activity did not reduce ZIKV infectious titers. In contrast, both the flavivirus dengue virus and the alphavirus Sindbis virus replicated to significantly higher titers in RNase L KO cells compared to wild-type (WT) cells. Using MAVS/RNase L double KO cells, we demonstrated that the absence of increased ZIKV production in RNase L KO cells was not due to compensation by enhanced type I interferon transcripts to thus inhibit virus production. Finally, when synthetic double-stranded RNA was detected by OAS3 to induce RNase L antiviral activity prior to ZIKV infection, we observed reduced ZIKV replication factory formation, as well as a 42-fold reduction in virus yield in WT but not RNase L KO cells. This study proposes that ZIKV evades RNase L antiviral activity by generating a viral genome reservoir protected from RNase L cleavage during early infection, allowing for sufficient virus production before RNase L activation is detectable. IMPORTANCE With the onset of the 2015 ZIKV outbreak, ZIKV pathogenesis has been of extreme global public health interest, and a better understanding of interactions with the host would provide insight into molecular mechanisms driving the severe neurological outcomes of ZIKV disease. Here is the initial report on the relationship between ZIKV and the host oligoadenylate synthetase-RNase L (OAS-RNase L) system, a potent antiviral pathway effective at restricting replication of diverse viruses. Our study elucidated a unique mechanism whereby ZIKV production is impervious to antiviral RNase L activity, through a mechanism of viral RNA protection that is not mimicked during infection with numerous other RNase L-activating viruses, thus identifying a distinct replication strategy potentially important for ZIKV pathogenesis.",,"['Whelan, Jillian N.', 'Li, Yize', 'Silverman, Robert H.', 'Weiss, Susan R.']",,,,
,PMC,Species-Specific Colocalization of Middle East Respiratory Syndrome Coronavirus Attachment and Entry Receptors,http://dx.doi.org/10.1128/JVI.00107-19,PMC6675889,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) uses the S1(B) domain of its spike protein to bind to dipeptidyl peptidase 4 (DPP4), its functional receptor, and its S1(A) domain to bind to sialic acids. The tissue localization of DPP4 in humans, bats, camelids, pigs, and rabbits generally correlates with MERS-CoV tropism, highlighting the role of DPP4 in virus pathogenesis and transmission. However, MERS-CoV S1(A) does not indiscriminately bind to all α2,3-sialic acids, and the species-specific binding and tissue distribution of these sialic acids in different MERS-CoV-susceptible species have not been investigated. We established a novel method to detect these sialic acids on tissue sections of various organs of different susceptible species by using nanoparticles displaying multivalent MERS-CoV S1(A). We found that the nanoparticles specifically bound to the nasal epithelial cells of dromedary camels, type II pneumocytes in human lungs, and the intestinal epithelial cells of common pipistrelle bats. Desialylation by neuraminidase abolished nanoparticle binding and significantly reduced MERS-CoV infection in primary susceptible cells. In contrast, S1(A) nanoparticles did not bind to the intestinal epithelium of serotine bats and frugivorous bat species, nor did they bind to the nasal epithelium of pigs and rabbits. Both pigs and rabbits have been shown to shed less infectious virus than dromedary camels and do not transmit the virus via either contact or airborne routes. Our results depict species-specific colocalization of MERS-CoV entry and attachment receptors, which may be relevant in the transmission and pathogenesis of MERS-CoV. IMPORTANCE MERS-CoV uses the S1(B) domain of its spike protein to attach to its host receptor, dipeptidyl peptidase 4 (DPP4). The tissue localization of DPP4 has been mapped in different susceptible species. On the other hand, the S1(A) domain, the N-terminal domain of this spike protein, preferentially binds to several glycotopes of α2,3-sialic acids, the attachment factor of MERS-CoV. Here we show, using a novel method, that the S1(A) domain specifically binds to the nasal epithelium of dromedary camels, alveolar epithelium of humans, and intestinal epithelium of common pipistrelle bats. In contrast, it does not bind to the nasal epithelium of pigs or rabbits, nor does it bind to the intestinal epithelium of serotine bats and frugivorous bat species. This finding supports the importance of the S1(A) domain in MERS-CoV infection and tropism, suggests its role in transmission, and highlights its potential use as a component of novel vaccine candidates.",,"['Widagdo, W.', 'Okba, Nisreen M. A.', 'Li, Wentao', 'de Jong, Alwin', 'de Swart, Rik L.', 'Begeman, Lineke', 'van den Brand, Judith M. A.', 'Bosch, Berend-Jan', 'Haagmans, Bart L.']",,,,
,PMC,Novel Function of Bluetongue Virus NS3 Protein in Regulation of the MAPK/ERK Signaling Pathway,http://dx.doi.org/10.1128/JVI.00336-19,PMC6675888,,,"Bluetongue virus (BTV) is an arbovirus transmitted by blood-feeding midges to a wide range of wild and domestic ruminants. In this report, we showed that BTV, through its nonstructural protein NS3 (BTV-NS3), is able to activate the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, as assessed by phosphorylation levels of ERK1/2 and the translation initiation factor eukaryotic translation initiation factor 4E (eIF4E). By combining immunoprecipitation of BTV-NS3 and mass spectrometry analysis from both BTV-infected and NS3-transfected cells, we identified the serine/threonine-protein kinase B-Raf (BRAF), a crucial player in the MAPK/ERK pathway, as a new cellular interactor of BTV-NS3. BRAF silencing led to a significant decrease in the MAPK/ERK activation by BTV, supporting a model wherein BTV-NS3 interacts with BRAF to activate this signaling cascade. This positive regulation acts independently of the role of BTV-NS3 in counteracting the induction of the alpha/beta interferon response. Furthermore, the intrinsic ability of BTV-NS3 to bind BRAF and activate the MAPK/ERK pathway is conserved throughout multiple serotypes/strains but appears to be specific to BTV compared to other members of Orbivirus genus. Inhibition of MAPK/ERK pathway with U0126 reduced viral titers, suggesting that BTV manipulates this pathway for its own replication. Altogether, our data provide molecular mechanisms that unravel a new essential function of NS3 during BTV infection. IMPORTANCE Bluetongue virus (BTV) is responsible of the arthropod-borne disease bluetongue (BT) transmitted to ruminants by blood-feeding midges. In this report, we found that BTV, through its nonstructural protein NS3 (BTV-NS3), interacts with BRAF, a key component of the MAPK/ERK pathway. In response to growth factors, this pathway promotes cell survival and increases protein translation. We showed that BTV-NS3 enhances the MAPK/ERK pathway, and this activation is BRAF dependent. Treatment of MAPK/ERK pathway with the pharmacologic inhibitor U0126 impairs viral replication, suggesting that BTV manipulates this pathway for its own benefit. Our results illustrate, at the molecular level, how a single virulence factor has evolved to target a cellular function to increase its viral replication.",,"['Kundlacz, Cindy', 'Pourcelot, Marie', 'Fablet, Aurore', 'Amaral Da Silva Moraes, Rayane', 'Léger, Thibaut', 'Morlet, Bastien', 'Viarouge, Cyril', 'Sailleau, Corinne', 'Turpaud, Mathilde', 'Gorlier, Axel', 'Breard, Emmanuel', 'Lecollinet, Sylvie', 'van Rijn, Piet A.', 'Zientara, Stephan', 'Vitour, Damien', 'Caignard, Grégory']",,,,
,PMC,A Yeast Suppressor Screen Used To Identify Mammalian SIRT1 as a Proviral Factor for Middle East Respiratory Syndrome Coronavirus Replication,http://dx.doi.org/10.1128/JVI.00197-19,PMC6675885,,,"Viral proteins must intimately interact with the host cell machinery during virus replication. Here, we used the yeast Saccharomyces cerevisiae as a system to identify novel functional interactions between viral proteins and eukaryotic cells. Our work demonstrates that when the Middle East respiratory syndrome coronavirus (MERS-CoV) ORF4a accessory gene is expressed in yeast it causes a slow-growth phenotype. ORF4a has been characterized as an interferon antagonist in mammalian cells, and yet yeast lack an interferon system, suggesting further interactions between ORF4a and eukaryotic cells. Using the slow-growth phenotype as a reporter of ORF4a function, we utilized the yeast knockout library collection to perform a suppressor screen where we identified the YDL042C/SIR2 yeast gene as a suppressor of ORF4a function. The mammalian homologue of SIR2 is SIRT1, an NAD-dependent histone deacetylase. We found that when SIRT1 was inhibited by either chemical or genetic manipulation, there was reduced MERS-CoV replication, suggesting that SIRT1 is a proviral factor for MERS-CoV. Moreover, ORF4a inhibited SIRT1-mediated modulation of NF-κB signaling, demonstrating a functional link between ORF4a and SIRT1 in mammalian cells. Overall, the data presented here demonstrate the utility of yeast studies for identifying genetic interactions between viral proteins and eukaryotic cells. We also demonstrate for the first time that SIRT1 is a proviral factor for MERS-CoV replication and that ORF4a has a role in modulating its activity in cells. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) initially emerged in 2012 and has since been responsible for over 2,300 infections, with a case fatality ratio of approximately 35%. We have used the highly characterized model system of Saccharomyces cerevisiae to investigate novel functional interactions between viral proteins and eukaryotic cells that may provide new avenues for antiviral intervention. We identify a functional link between the MERS-CoV ORF4a proteins and the YDL042C/SIR2 yeast gene. The mammalian homologue of SIR2 is SIRT1, an NAD-dependent histone deacetylase. We demonstrate for the first time that SIRT1 is a proviral factor for MERS-CoV replication and that ORF4a has a role in modulating its activity in mammalian cells.",,"['Weston, Stuart', 'Matthews, Krystal L.', 'Lent, Rachel', 'Vlk, Alexandra', 'Haupt, Rob', 'Kingsbury, Tami', 'Frieman, Matthew B.']",,,,
,PMC,Disease modelling in human organoids,http://dx.doi.org/10.1242/dmm.039347,PMC6679380,31383635,CC BY,"The past decade has seen an explosion in the field of in vitro disease modelling, in particular the development of organoids. These self-organizing tissues derived from stem cells provide a unique system to examine mechanisms ranging from organ development to homeostasis and disease. Because organoids develop according to intrinsic developmental programmes, the resultant tissue morphology recapitulates organ architecture with remarkable fidelity. Furthermore, the fact that these tissues can be derived from human progenitors allows for the study of uniquely human processes and disorders. This article and accompanying poster highlight the currently available methods, particularly those aimed at modelling human biology, and provide an overview of their capabilities and limitations. We also speculate on possible future technological advances that have the potential for great strides in both disease modelling and future regenerative strategies.",2019 Jul 1,"['Lancaster, Madeline A.', 'Huch, Meritxell']",Dis Model Mech,,,
,PMC,IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes,http://dx.doi.org/10.1172/JCI126363,PMC6715373,,,"Type 1 IFNs (IFN-I) generally protect mammalian hosts from virus infections, but in some cases, IFN-I is pathogenic. Because IFN-I is protective, it is commonly used to treat virus infections for which no specific approved drug or vaccine is available. The Middle East respiratory syndrome–coronavirus (MERS-CoV) is such an infection, yet little is known about the role of IFN-I in this setting. Here, we show that IFN-I signaling is protective during MERS-CoV infection. Blocking IFN-I signaling resulted in delayed virus clearance, enhanced neutrophil infiltration, and impaired MERS-CoV–specific T cell responses. Notably, IFN-I administration within 1 day after infection (before virus titers peak) protected mice from lethal infection, despite a decrease in IFN-stimulated gene (ISG) and inflammatory cytokine gene expression. In contrast, delayed IFN-β treatment failed to effectively inhibit virus replication; increased infiltration and activation of monocytes, macrophages, and neutrophils in the lungs; and enhanced proinflammatory cytokine expression, resulting in fatal pneumonia in an otherwise sublethal infection. Together, these results suggest that the relative timing of the IFN-I response and maximal virus replication is key in determining outcomes, at least in infected mice. By extension, IFN-αβ or combination therapy may need to be used cautiously to treat viral infections in clinical settings.",,"['Channappanavar, Rudragouda', 'Fehr, Anthony R.', 'Zheng, Jian', 'Wohlford-Lenane, Christine', 'Abrahante, Juan E.', 'Mack, Matthias', 'Sompallae, Ramakrishna', 'McCray, Paul B.', 'Meyerholz, David K.', 'Perlman, Stanley']",,,,
,PMC,Alternate Nucleic Acid Targets Can Be Used To Create a Composite Standard To Evaluate Clinical Performance of Nucleic Acid Amplification Tests,http://dx.doi.org/10.1128/JCM.00661-19,PMC6663904,,,"Evaluating the clinical performance of a new nucleic acid amplification test (NAAT) for Mycoplasma genitalium, B. Kirkconnell, B. Weinbaum, K. Santos, T. Le Nguyen, et al. (J Clin Microbiol 57:e00264-19, 2019, https://doi.org/10.1128/JCM.00264-19) created 3 alternate NAATs that detected other unique M. genitalium gene targets. Lacking a reference standard, they used the consensus of results with those 3 NAATs as the comparator. This approach could be a new paradigm to evaluate new NAATs when there is no previously defined reference standard.",,"['Schachter, Julius', 'Chernesky, Max']",,,,
,PMC,MicroRNA 155 Contributes to Host Immunity against Leishmania donovani but Is Not Essential for Resolution of Infection,http://dx.doi.org/10.1128/IAI.00307-19,PMC6652779,,,"CD4(+) T helper 1 (Th1) cells producing interferon gamma (IFN-γ) are critical for the resolution of visceral leishmaniasis (VL). MicroRNA 155 (miR155) promotes CD4(+) Th1 responses and IFN-γ production by targeting suppressor of cytokine signaling-1 (SOCS1) and Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP-1) and therefore could play a role in the resolution of VL. To determine the role of miR155 in VL, we monitored the course of Leishmania donovani infection in miR155 knockout (miR155KO) and wild-type (WT) C57BL/6 mice. miR155KO mice displayed significantly higher liver and spleen parasite loads than WT controls and showed impaired hepatic granuloma formation. However, parasite growth eventually declined in miR155KO mice, suggesting the induction of a compensatory miR155-independent antileishmanial pathway. Leishmania antigen-stimulated splenocytes from miR155KO mice produced significantly lower levels of Th1-associated IFN-γ than controls. Interestingly, at later time points, levels of Th2-associated interleukin-4 (IL-4) and IL-10 were also lower in miR155KO splenocyte supernatants than in WT mice. On the other hand, miR155KO mice displayed significantly higher levels of IFN-γ, iNOS, and TNF-α gene transcripts in their livers than WT mice, indicating that distinct organ-specific antiparasitic mechanisms were involved in control of L. donovani infection in miR155KO mice. Throughout the course of infection, organs of miR155KO mice showed significantly more PDL1-expressing Ly6C(hi) inflammatory monocytes than WT mice. Conversely, blockade of Ly6C(hi) inflammatory monocyte recruitment in miR155KO mice significantly reduced parasitic loads, indicating that these cells contributed to disease susceptibility. In conclusion, we found that miR155 contributes to the control of L. donovani but is not essential for infection resolution.",,"['Varikuti, Sanjay', 'Natarajan, Gayathri', 'Volpedo, Greta', 'Singh, Bhawana', 'Hamza, Omar', 'Messick, Gretchen V.', 'Guerau-de-Arellano, Mireia', 'Papenfuss, Tracey L.', 'Oghumu, Steve', 'Satoskar, Abhay R.']",,,,
,PMC,Viral Coinfection Replaces Effects of Suilysin on Streptococcus suis Adherence to and Invasion of Respiratory Epithelial Cells Grown under Air-Liquid Interface Conditions,http://dx.doi.org/10.1128/IAI.00350-19,PMC6652749,,,"Streptococcus suis is an important zoonotic pathogen which can infect humans and pigs worldwide, posing a potential risk to global public health. Suilysin, a pore-forming cholesterol-dependent cytolysin, is considered to play an important role in the pathogenesis of S. suis infections. It is known that infection with influenza A viruses may favor susceptibility to secondary bacterial infection, resulting in more severe disease and increased mortality. However, the molecular mechanisms underlying these coinfections are incompletely understood. Applying highly differentiated primary porcine respiratory epithelial cells grown under air-liquid interface (ALI) conditions, we analyzed the contribution of swine influenza viruses (SIV) to the virulence of S. suis, with a special focus on its cytolytic toxin, suilysin. We found that during secondary bacterial infection, suilysin of S. suis contributed to the damage of well-differentiated respiratory epithelial cells in the early stage of infection, whereas the cytotoxic effects induced by SIV became prominent at later stages of infection. Prior infection by SIV enhanced the adherence to and colonization of porcine airway epithelial cells by a wild-type (wt) S. suis strain and a suilysin-negative S. suis mutant in a sialic acid-dependent manner. A striking difference was observed with respect to bacterial invasion. After bacterial monoinfection, only the wt S. suis strain showed an invasive phenotype, whereas the mutant remained adherent. When the epithelial cells were preinfected with SIV, the suilysin-negative mutant also showed an invasion capacity. Therefore, we propose that coinfection with SIV may compensate for the lack of suilysin in the adherence and invasion process of suilysin-negative S. suis.",,"['Meng, Fandan', 'Tong, Jie', 'Vötsch, Désirée', 'Peng, Ju-Yi', 'Cai, Xuehui', 'Willenborg, Maren', 'Herrler, Georg', 'Wu, Nai-Huei', 'Valentin-Weigand, Peter']",,,,
,PMC,Projection Word Embedding Model With Hybrid Sampling Training for Classifying ICD-10-CM Codes: Longitudinal Observational Study,http://dx.doi.org/10.2196/14499,PMC6683650,31339103,CC BY,"BACKGROUND: Most current state-of-the-art models for searching the International Classification of Diseases, Tenth Revision Clinical Modification (ICD-10-CM) codes use word embedding technology to capture useful semantic properties. However, they are limited by the quality of initial word embeddings. Word embedding trained by electronic health records (EHRs) is considered the best, but the vocabulary diversity is limited by previous medical records. Thus, we require a word embedding model that maintains the vocabulary diversity of open internet databases and the medical terminology understanding of EHRs. Moreover, we need to consider the particularity of the disease classification, wherein discharge notes present only positive disease descriptions. OBJECTIVE: We aimed to propose a projection word2vec model and a hybrid sampling method. In addition, we aimed to conduct a series of experiments to validate the effectiveness of these methods. METHODS: We compared the projection word2vec model and traditional word2vec model using two corpora sources: English Wikipedia and PubMed journal abstracts. We used seven published datasets to measure the medical semantic understanding of the word2vec models and used these embeddings to identify the three–character-level ICD-10-CM diagnostic codes in a set of discharge notes. On the basis of embedding technology improvement, we also tried to apply the hybrid sampling method to improve accuracy. The 94,483 labeled discharge notes from the Tri-Service General Hospital of Taipei, Taiwan, from June 1, 2015, to June 30, 2017, were used. To evaluate the model performance, 24,762 discharge notes from July 1, 2017, to December 31, 2017, from the same hospital were used. Moreover, 74,324 additional discharge notes collected from seven other hospitals were tested. The F-measure, which is the major global measure of effectiveness, was adopted. RESULTS: In medical semantic understanding, the original EHR embeddings and PubMed embeddings exhibited superior performance to the original Wikipedia embeddings. After projection training technology was applied, the projection Wikipedia embeddings exhibited an obvious improvement but did not reach the level of original EHR embeddings or PubMed embeddings. In the subsequent ICD-10-CM coding experiment, the model that used both projection PubMed and Wikipedia embeddings had the highest testing mean F-measure (0.7362 and 0.6693 in Tri-Service General Hospital and the seven other hospitals, respectively). Moreover, the hybrid sampling method was found to improve the model performance (F-measure=0.7371/0.6698). CONCLUSIONS: The word embeddings trained using EHR and PubMed could understand medical semantics better, and the proposed projection word2vec model improved the ability of medical semantics extraction in Wikipedia embeddings. Although the improvement from the projection word2vec model in the real ICD-10-CM coding task was not substantial, the models could effectively handle emerging diseases. The proposed hybrid sampling method enables the model to behave like a human expert.",2019 Jul 23,"['Lin, Chin', 'Lou, Yu-Sheng', 'Tsai, Dung-Jang', 'Lee, Chia-Cheng', 'Hsu, Chia-Jung', 'Wu, Ding-Chung', 'Wang, Mei-Chuen', 'Fang, Wen-Hui']",JMIR Med Inform,,,
,PMC,Infectious Chikungunya Virus (CHIKV) with a Complete Capsid Deletion: a New Approach for a CHIKV Vaccine,http://dx.doi.org/10.1128/JVI.00504-19,PMC6639289,,,"Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes epidemics of debilitating disease worldwide. Currently, there are no licensed vaccines or antivirals available against CHIKV infection. In this study, we generated a novel live attenuated vaccine (LAV) candidate for CHIKV with a complete deficiency of capsid (ΔC-CHIKV). It could propagate in BHK-21 cells, and had antigenic properties similar to those of native CHIKV. Vaccination of either immunocompromised IFNAR(−/−) mice or immunocompetent C57BL/6 mice with a single dose of ΔC-CHIKV conferred complete protection upon challenge with wild-type (WT) CHIKV. Taken together, this vaccine candidate appeared to be safe and efficacious, representing a novel strategy for CHIKV vaccine design. IMPORTANCE Currently, there is no licensed vaccine against CHIKV infection. An ideal CHIKV vaccine should generate an optimal balance between efficacy and safety. Live attenuated vaccines that can elicit strong immune responses often involve a trade-off of reduced safety. Here, a novel live attenuated vaccine candidate for CHIKV lacking the entire capsid gene, ΔC-CHIKV, was developed. It was demonstrated to be genetically stable, highly attenuated, immunogenic, and able to confer complete protection against lethal CHIKV challenge after a single dose of immunization. Such an infectious vaccine candidate devoid of capsid provides a novel strategy for the development of a live attenuated CHIKV vaccine.",,"['Zhang, Ya-Nan', 'Deng, Cheng-Lin', 'Li, Jia-Qi', 'Li, Na', 'Zhang, Qiu-Yan', 'Ye, Han-Qing', 'Yuan, Zhi-Ming', 'Zhang, Bo']",,,,
,PMC,Junín Virus Promotes Autophagy To Facilitate the Virus Life Cycle,http://dx.doi.org/10.1128/JVI.02307-18,PMC6639288,,,"Junín virus (JUNV), a member of the family Arenaviridae, is the etiological agent of Argentine hemorrhagic fever (AHF), a potentially deadly endemic-epidemic disease affecting the population of the most fertile farming land of Argentina. Autophagy is a degradative process with a crucial antiviral role; however, several viruses subvert the pathway to their benefit. We determined the role of autophagy in JUNV-infected cells by analyzing LC3, a cytoplasmic protein (LC3-I) that becomes vesicle membrane associated (LC3-II) upon induction of autophagy. Cells overexpressing enhanced green fluorescent protein (EGFP)-LC3 and infected with JUNV showed an increased number of LC3 punctate structures, similar to those obtained after starvation or bafilomycin A1 treatment, which leads to autophagosome induction or accumulation, respectively. We also monitored the conversion of LC3-I to LC3-II, observing LC3-II levels in JUNV-infected cells similar to those observed in starved cells. Additionally, we kinetically studied the number of LC3 dots after JUNV infection and found that the virus activated the pathway as early as 2 h postinfection (p.i.), whereas the UV-inactivated virus did not induce the pathway. Cells subjected to starvation or pretreated with rapamycin, a pharmacological autophagy inductor, enhanced virus yield. Also, we assayed the replication capacity of JUNV in Atg5 knockout or Beclin 1 knockdown cells (both critical components of the autophagic pathway) and found a significant decrease in JUNV replication. Taken together, our results constitute the first study indicating that JUNV infection induces an autophagic response, which is functionally required by the virus for efficient propagation. IMPORTANCE Mammalian arenaviruses are zoonotic viruses that cause asymptomatic and persistent infections in their rodent hosts but may produce severe and lethal hemorrhagic fevers in humans. Currently, there are neither effective therapeutic options nor effective vaccines for viral hemorrhagic fevers caused by human-pathogenic arenaviruses, except the vaccine Candid no. 1 against Argentine hemorrhagic fever (AHF), licensed for human use in areas of endemicity in Argentina. Since arenaviruses remain a severe threat to global public health, more in-depth knowledge of their replication mechanisms would improve our ability to fight these viruses. Autophagy is a lysosomal degradative pathway involved in maintaining cellular homeostasis, representing powerful anti-infective machinery. We show, for the first time for a member of the family Arenaviridae, a proviral role of autophagy in JUNV infection, providing new knowledge in the field of host-virus interaction. Therefore, modulation of virus-induced autophagy could be used as a strategy to block arenavirus infections.",,"['Roldán, Julieta S.', 'Candurra, Nélida A.', 'Colombo, María I.', 'Delgui, Laura R.']",,,,
,PMC,Porcine Reproductive and Respiratory Syndrome Virus nsp11 Antagonizes Type I Interferon Signaling by Targeting IRF9,http://dx.doi.org/10.1128/JVI.00623-19,PMC6639278,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus from the Nidovirales order that causes reproductive failure and respiratory disease in pigs and poses a constant threat to the global pig industry. The PRRSV-encoded nonstructural protein 11 (nsp11) is a nidovirus-specific endoribonuclease (NendoU) that is conserved throughout the Arteriviridae and Coronaviridae families. Previously, our research and that of others demonstrated that PRRSV nsp11 inhibits type I interferon (IFN) production through NendoU activity-dependent mechanisms. Here, we found that PRRSV nsp11 also inhibited IFN-stimulated response element (ISRE) promoter activity and subsequent transcription of IFN-stimulated genes (ISGs). Detailed analysis showed that nsp11 targeted interferon regulatory factor 9 (IRF9), but not transducer and activator of transcription 1 (STAT1) or STAT2, key molecules in the type I IFN signaling pathway. Furthermore, the nsp11-IRF9 interaction impaired the formation and nuclear translocation of the transcription factor complex IFN-stimulated gene factor 3 (ISGF3) in both nsp11-overexpressed and PRRSV-infected cells. Importantly, nsp11 mutations (H129A, H144A, and K173A) that ablate NendoU activity or its cell cytotoxicity also interacted with IRF9 and retained the ability to block IFN signaling, indicating that the nsp11-IRF9 interaction is independent of NendoU activity or cell cytotoxicity of nsp11. Taking the results together, our study demonstrated that PRRSV nsp11 antagonizes type I IFN signaling by targeting IRF9 via a NendoU activity-independent mechanism, and this report describes a novel strategy evolved by PRRSV to counteract host innate antiviral responses, revealing a potential new function for PRRSV nsp11 in type I IFN signaling. IMPORTANCE The nidovirus-specific endoribonuclease (NendoU) encoded by PRRSV nonstructural protein 11 (nsp11) is a unique NendoU of nidoviruses that infect vertebrates; thus, it is an attractive target for the development of antinidovirus drugs. Previous studies have revealed that the NendoU of nidoviruses, including porcine reproductive and respiratory syndrome virus (PRRSV) and human coronavirus 229E (HCoV-229E), acts as a type I interferon (IFN) antagonist. Here, for the first time, we demonstrated that overexpression of PRRSV nsp11 also inhibits IFN signaling by targeting the C-terminal interferon regulatory factor (IRF) association domain of IRF9. This interaction impaired the ability of IRF9 to form the transcription factor complex IFN-stimulated gene factor 3 (ISGF3) and to act as a signaling protein of IFN signaling. Collectively, our data identify IRF9 as a natural target of PRRSV NendoU and reveal a novel mechanism evolved by an arterivirus to counteract innate immune signaling.",,"['Wang, Dang', 'Chen, Jiyao', 'Yu, Chaoliang', 'Zhu, Xinyu', 'Xu, Shangen', 'Fang, Liurong', 'Xiao, Shaobo']",,,,
,PMC,Engineering a Live Attenuated Porcine Epidemic Diarrhea Virus Vaccine Candidate via Inactivation of the Viral 2'-O-Methyltransferase and the Endocytosis Signal of the Spike Protein,http://dx.doi.org/10.1128/JVI.00406-19,PMC6639265,,,"Porcine epidemic diarrhea virus (PEDV) causes high mortality in neonatal piglets; however, effective and safe vaccines are still not available. We hypothesized that inactivation of the 2′-O-methyltransferase (2′-O-MTase) activity of nsp16 and the endocytosis signal of the spike protein attenuates PEDV yet retains its immunogenicity in pigs. We generated a recombinant PEDV, KDKE(4A), with quadruple alanine substitutions in the catalytic tetrad of the 2′-O-MTase using a virulent infectious cDNA clone, icPC22A, as the backbone. Next, we constructed another mutant, KDKE(4A)-SYA, by abolishing the endocytosis signal of the spike protein of KDKE(4A). Compared with icPC22A, the KDKE(4A) and KDKE(4A)-SYA mutants replicated less efficiently in vitro but induced stronger type I and type III interferon responses. The pathogenesis and immunogenicities of the mutants were evaluated in gnotobiotic piglets. The virulence of KDKE(4A)-SYA and KDKE(4A) was significantly reduced compared with that of icPC22A. Mortality rates were 100%, 17%, and 0% in the icPC22A-, KDKE(4A)-, and KDKE(4A)-SYA-inoculated groups, respectively. At 21 days postinoculation (dpi), all surviving pigs were challenged orally with a high dose of icPC22A. The KDKE(4A)-SYA- and KDKE(4A)-inoculated pigs were protected from the challenge, because no KDKE(4A)-SYA- and one KDKE(4A)-inoculated pig developed diarrhea whereas all the pigs in the mock-inoculated group had severe diarrhea, and 33% of them died. Furthermore, we serially passaged the KDKE(4A)-SYA mutant in pigs three times and did not find any reversion of the introduced mutations. The data suggest that KDKE(4A)-SYA may be a PEDV vaccine candidate. IMPORTANCE PEDV is the most economically important porcine enteric viral pathogen and has caused immense economic losses in the pork industries in many countries. Effective and safe vaccines are desperately required but still not available. 2′-O-MTase (nsp16) is highly conserved among coronaviruses (CoVs), and the inactivation of nsp16 in live attenuated vaccines has been attempted for several betacoronaviruses. We show that inactivation of both 2′-O-MTase and the endocytosis signal of the spike protein is an approach to designing a promising live attenuated vaccine for PEDV. The in vivo passaging data also validated the stability of the KDKE(4A)-SYA mutant. KDKE(4A)-SYA warrants further evaluation in sows and their piglets and may be used as a platform for further optimization. Our findings further confirmed that nsp16 can be a universal target for CoV vaccine development and will aid in the development of vaccines against other emerging CoVs.",,"['Hou, Yixuan', 'Ke, Hanzhong', 'Kim, Jineui', 'Yoo, Dongwan', 'Su, Yunfang', 'Boley, Patricia', 'Chepngeno, Juliet', 'Vlasova, Anastasia N.', 'Saif, Linda J.', 'Wang, Qiuhong']",,,,
,PMC,The anatomy and immunology of vasculature in the central nervous system,http://dx.doi.org/10.1126/sciimmunol.aav0492,PMC6816468,,,"Barriers between circulation and the central nervous system (CNS) play a key role in the development and modulation of CNS immune responses. Structural variations in the vasculature traversing different anatomical regions within the CNS strongly influence where and how CNS immune responses first develop. Here, we provide an overview of cerebrovascular anatomy, focusing on the blood-CNS interface and how anatomical variations influence steady-state immunology in the compartment. We then discuss how CNS vasculature is affected by and influences the development of different pathophysiological states, such as CNS autoimmune disease, cerebrovascular injury, cerebral ischemia, and infection.",,"['Mastorakos, Panagiotis', 'McGavern, Dorian']",,,,
,PMC,"Twitter Conversations and English News Media Reports on Poliomyelitis in Five Different Countries, January 2014 to April 2015",http://dx.doi.org/10.7812/TPP/18-181,PMC6636457,,,"INTRODUCTION: Twitter and media coverage on poliomyelitis help maintain global support for its eradication. OBJECTIVE: To test our hypothesis that themes of polio-related tweets and media articles would differ by location of interest (hashtag of country name mentioned in the tweet; country name mentioned in media articles) but would be similar to each other (tweets and media articles) for each location of interest. METHODS: We retrospectively examined a 40% random sample of Twitter data containing the hashtag #polio from January 1, 2014, to April 30, 2015 (N = 79,333), from which we extracted 5 subcorpora each with a co-occurring hashtag #India (n = 5027), #Iraq (n = 1238), #Nigeria (n = 1364), #Pakistan (n = 11,427), and #Syria (n = 2952). We also retrieved and categorized 73 polio-related English-language news stories from within the same timeframe. We assessed the association between polio-related English news themes and the Twitter content. Descriptive analyses and unsupervised machine learning (latent Dirichlet allocation modeling) were conducted on the 5 Twitter subcorpora. RESULTS: The results of the latent Dirichlet allocation modeling on the specific subcorpora with country co-occurring hashtags showed significant differences between the 5 countries in terms of content. English mass media content focused largely on violence/conflicts and cases of polio, whereas social media focused on eradication and vaccination efforts along with celebrations. DISCUSSION: Contrary to our hypothesis, our evidence suggests Twitter content differs significantly from English mass media content. Evidence from our study helps inform media monitoring and communications surveillance during global public health crises, such as infectious disease outbreaks, as well as reactions to health promotion campaigns.",,"['Schaible, Braydon J', 'Snook, Kassandra R', 'Yin, Jingjing', 'Jackson, Ashley M', 'Ahweyevu, Jennifer O', 'Chong, Muhling', 'Tse, Zion Tsz Ho', 'Liang, Hai', 'Fu, King-Wa', 'Fung, Isaac Chun-Hai']",,,,
,PMC,Instructions for Authors,http://dx.doi.org/10.1097/CM9.0000000000000324,PMC6616236,,,,,,,,,
,PMC,A public health enhanced surveillance system for a mass gathering event,http://dx.doi.org/10.45745/ccdr.v45i78a05,PMC6615436,,,"BACKGROUND: From June 7 to June 9, 2018, a G7 Summit was held in the Canadian province of Quebec. This international political mass gathering event posed a number of potential risks to public health. OBJECTIVE: To assess three additional monitoring strategies to detect public health threats during a mass gathering event. INTERVENTION: In addition to routine public health monitoring, a partnership was created and three monitoring strategies were put in place three days before, during and six days after the G7 event: the analysis of data on the presenting complaint and discharge diagnosis from 11 emergency departments in the area using the logical Early Aberration Reporting System; the daily polling of key health partners with an online questionnaire; and the analysis of calls to Info-Santé, a government-run telephone consultation service for the public regarding health and social issues. RESULTS: Emergency room data produced 78 alerts from the presenting complaints and 39 alerts from the discharge diagnoses. Of these 117 alerts, two were investigated (one in the respiratory and one in the neurological-muscular categories) and no other interventions were required. With a few exceptions, all of the health partners completed the online survey each day and no signal of concern was generated. Compared with historical data, no increase or differences in calls to Info-Santé were detected during the monitoring period. CONCLUSION: The three additional monitoring strategies developed to detect events of public health importance during the 2018 G7 Summit in Quebec were successful in gathering timely data for analysis. Close collaboration and good participation from the different partners were essential to this project. However, because no public health event occurred, it was not possible to determine whether the enhanced surveillance system had sufficient speed and sensitivity for timely detection and response.",,"['Huot, C', 'Paradis, A', 'Hammond-Collins, K', 'Bélair, MA', 'Villeneuve, J', 'Brousseau, N', 'Goupil-Sormany, I', 'Riffon, J']",,,,
,PMC,Considerations for the design of vaccine efficacy trials during public health emergencies,http://dx.doi.org/10.1126/scitranslmed.aat0360,PMC6613811,,,"Public Health Emergencies (PHEs) provide a complex and challenging environment for vaccine evaluation. Under the R&D Blueprint Plan of Action, the World Health Organization (WHO) has convened a group of experts to agree on standard procedures to rapidly evaluate experimental vaccines during PHEs while maintaining the highest scientific and ethical standards. The Blueprint priority diseases, selected for their likelihood to cause PHEs and the lack of adequate medical countermeasures, were used to frame our methodological discussions. Here, we outline major vaccine study designs to be used in PHEs and summarize high-level recommendations for their use in this setting. We recognize that the epidemiology and transmission dynamics of the Blueprint priority diseases may be highly uncertain and that the unique characteristics of the vaccines and outbreak settings may affect our study design. To address these challenges, our group underscores the need for novel, flexible, and responsive trial designs. We conclude that assignment to study groups using randomization is a key principle underlying rigorous study design and should be utilized except in exceptional circumstances. Advance planning for vaccine trial designs is critical for rapid and effective response to a PHE and to advance knowledge to address and mitigate future PHEs.",,"['Dean, Natalie E.', 'Gsell, Pierre-Stéphane', 'Brookmeyer, Ron', 'Gruttola, Victor De', 'Donnelly, Christl A.', 'Halloran, M. Elizabeth', 'Jasseh, Momodou', 'Nason, Martha', 'Riveros, Ximena', 'Watson, Conall H.', 'Henao-Restrepo, Ana Maria', 'Longini, Ira M.']",,,,
,PMC,Characteristics and outcome of viral pneumonia caused by influenza and Middle East respiratory syndrome-coronavirus infections: A 4-year experience from a tertiary care center,http://dx.doi.org/10.4103/atm.ATM_179_18,PMC6611200,31333767,CC BY-NC-SA,"BACKGROUND: After the emergence of new influenza viruses, the morbidity and mortality of viral pneumonia have received a great attention. OBJECTIVES: The objective of this study is to describe the epidemiologic, clinical and laboratory changes, and outcomes of viral pneumonia caused by influenza and the Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. METHODS: In a retrospective cohort study, the medical records of all patients diagnosed with viral pneumonia at Prince Sultan Military Medical City, Riyadh, Saudi Arabia, during the period from January 2012 to December 2015 were screened. Cases who were > 18 years old and were confirmed by a respiratory viral panel to have viral pneumonia either MERS-CoV or influenza viruses were included in the analysis. Sociodemographic, clinical, laboratory, and outcome data were extracted from patients' medical files. The data were analyzed descriptively and inferentially to identify the predictors of poor outcome. RESULTS: A total of 448 patients with confirmed viral pneumonia were included, of those, 216 (48.2%) were caused by influenza A (non H1N1)/influenza B, 150 (33.5%) by H1N1, and 82 (18.3%) by MERS-CoV. The majority of patients presented with fever (82%), shortness of breath (64%), and flu-like symptoms (54.9%), particularly in MERS-CoV infected cases (92%). The peak incidence of viral pneumonia was in early spring and autumn. The mortality rate was 13.8%, and it was significantly higher among MERS-CoV cases. The predictors of death were age > 65 years, male gender, and associated comorbidities particularly diabetes mellitus, hypertension, and chronic kidney diseases. The number of comorbid illnesses was directly related to the increase in mortality in this group of patients. CONCLUSION: Viral pneumonia caused by influenza and MERS-CoV carries a high mortality rate, particularly among MERS-CoV infected cases. Old age, male gender, and comorbid illnesses are predictors of poor outcome. Routine testing for newly emergent viruses is warranted for adults who have been hospitalized with pneumonia.",2019 Jul-Sep,"['Al-Baadani, Abeer M.', 'Elzein, Fatehi E.', 'Alhemyadi, Salwa A.', 'Khan, Osama A.', 'Albenmousa, Ali H.', 'Idrees, Majdy M.']",Ann Thorac Med,,,
,PMC,Increased neutrophils and IL-17A in a rare organizing pneumonia secondary to extrapulmonary operation,http://dx.doi.org/10.21037/atm.2019.06.20,PMC6694240,,,"Organizing pneumonia (OP) is a clinical syndrome caused by various diseases. The most common causes are infection, connective tissue disease, radiation therapy, drug reaction and thoracic operation. Herein, we describe the case of a patient that developed OP after fracture internal fixation. The case was confirmed to be OP by computer tomographic (CT)-guided percutaneous needle lung biopsy, and other causes of OP were excluded. After the initiation of corticosteroid therapy, marked clinical and radiographic improvements occurred. In addition, we discovered increased neutrophils and IL-17A in the lung tissue of the patient. To the best of our knowledge, this is the first case report about OP secondary to extrapulmonary operation.",,"['Wu, Chaojie', 'Xu, Kun', 'Wang, Zhengxia', 'Chen, Zhongqi', 'Sun, Zhixiao', 'Yu, Wenqing', 'Ji, Ningfei', 'Huang, Mao', 'Zhang, Mingshun']",,,,
,PMC,Sterile Parts of Operating Gown during Lower Limb Joint Replacement Surgery,,PMC6686066,,,"BACKGROUND: The prevention of surgical site infection is one of the most concerning issues in operating rooms. Surgical gowns are worn as one of the intraoperative strategies for infection prevention. The present study investigated whether the gowns remained sterile during the surgical procedure. Furthermore, this study examined which parts of the surgical gown were more prone to contamination. METHODS: The sterility of the gowns was investigated during eight total joint arthroplasties all of which were performed by four surgeons. The samples were taken from the arms and frontal part of the sterile gowns pre- and postoperatively. In the anterior surface of the gown, the sampling was initiated at a strip with 50 cm height from the ground followed by the strips with 15 cm distances from caudal to cephalad. Furthermore, the frontal part of the gown was divided into three parts in relation to the operating room table. Finally, the contamination rate was evaluated in each part. A semiquantitative method was used for the analysis of bacterial culture. RESULTS: Before the operation, there were four samples tested positive for bacterial culture (1.06%). All of these samples were taken from the most proximal strip near the neckline. After the surgery, the rate of contamination in the strips on the frontal part of the gown was reported as 3.1% to 53%. Based on the operating table, the contamination rate was 35.9%, 8.9%, and 47.3% in the distal, middle, and proximal parts of the gown, respectively. The contamination rate at the elbow crease was 23%, and at 5 and 10 cm above the creases were 24% and 36%, respectively. CONCLUSION: The high rate of gown contamination during the operation is concerning. However, part of the gown that was in contact with the operating room table remained clean most of the time. More safe strategies should be used for infection prevention in operating rooms.",,"['Qoreishi, Mohamad', 'Abbasian, Mohammadreza', 'Safdari, Farshad']",,,,
,PMC,Strengthening Public Health Partnerships in India: Envisioning the Role of Law Enforcement During Public Health Emergencies,http://dx.doi.org/10.4103/ijcm.IJCM_110_19,PMC6776937,31602100,CC BY-NC-SA,"Unique challenges posed by complex public health emergencies have often called for institutions, responsible for restoring health, well-being, and order among affected populations, to realign their operating procedures and work in concordance with each other. To ensure optimal health, the growth of the individuals and societies, and development in a greater sense, it is essential to understand the scope of collaboration between law enforcement agencies and public health institutions during emergencies and their aftermath. To foster such partnerships, policy-level advocacy to overcome challenges posed by existing policies and legislation that limit the autonomy of the law enforcement and public health institutions for making informed decisions would be necessary. Human resources working at different levels should be sensitized about the nature and significance of the kind of collaboration, and they should be allowed to express and clarify their doubts about the same. Evidence-based standard operating procedures should be developed for different cadres of professionals, keeping harmony with the operational diversities. Critical issues such as financing the ventures, coordinating and implementing the protocols and projects, following up the cases and suspects, and examining every scenario using evidence-based scientific and legal methodologies would be crucial for the success of such collaborations.",2019 Jul-Sep,"['Sharma, Rachit', 'Hossain, Md. Mahbub']",Indian J Community Med,,,
,PMC,Acne Management Guidelines by the Dermatological Society of Singapore,,PMC6715335,,,"Due to the multiethnic patient population with varying skin types in Singapore, clinicians often find the management of acne in their patients to be challenging. The authors developed these guidelines to provide comprehensive advice on individualized acne treatment and to provide a reference guide for all doctors who treat patients of Asian descent. Unique features of acne in Singapore are highlighted. We address concerns such as diet, special population needs, and the benefits, side effects, risks, and cost-effectiveness of currently available acne treatments. These treatment guidelines outline recommendations for the diagnosis, grading, and treatment of children, adolescents, and adults with acne of varying severity, and include advice pertaining to the use of cosmeceuticals and management of scars.",,"['Oon, Hazel H.', 'Wong, Su-Ni', 'Aw, Derrick Chen Wee', 'Cheong, Wai Kwong', 'Goh, Chee Leok', 'Tan, Hiok Hee']",,,,
,PMC,Content validity of the newly developed risk assessment tool for religious mass gathering events in an Indian setting (Mass Gathering Risk Assessment Tool-MGRAT),http://dx.doi.org/10.4103/jfmpc.jfmpc_380_19,PMC6691416,31463231,CC BY-NC-SA,"BACKGROUND: Risk assessment (RA) for mass gathering events is crucial to identify potential health hazards. It aids in planning and response activities specific to the event but is often overlooked by the event organizers. This paper reports the content validity process of a newly developed tool called Mass Gathering Risk Assessment Tool (MGRAT), which intends to assess the risks associated with religious mass gathering events in Indian settings. METHODS: Qualitative approach was followed to identify the risks associated with mass gathering events and to identify the domains and items to be included in the RA tool. The draft tool was shared with six experts who were selected by the convenient method; selected experts were requested to assess the tool and give their comments about the domains, items, relevant responses, and overall presentation of the tool using content validity questionnaire. Content validity index and Fleiss kappa statistics were calculated to assess the agreement between multiple raters. RESULTS: Agreement proportion expressed as scale-level content validity index (S-CVI) calculated by the averaging method is 0.92. S-CVI; calculated by universal agreement is 0.78. Fleiss kappa statistics to measure the agreement between multiple experts after adjusting the component of the chance agreement is 0.522 (95% CI: 0.417, 0.628, P value: 0.001). CONCLUSION: MGRAT is a valid tool, which has an appropriate level of content validity. As the number of raters increases, there will be difficulty in achieving consensus among all the items, which is the reason for lower Content Validity Index/Universal Average (CVI/UA) when compared with Content Validity Index/Average (CVI/Ave). Fleiss kappa statistics also indicated moderate agreement among the raters beyond the chance agreement, which also supports the appropriate content validity of MGRAT.",2019 Jul,"['Sharma, Upasana', 'Desikachari, BR', 'Sarma, Sankara']",J Family Med Prim Care,,,
,PMC,Human Monoclonal Antibodies Potently Neutralize Zika Virus and Select for Escape Mutations on the Lateral Ridge of the Envelope Protein,http://dx.doi.org/10.1128/JVI.00405-19,PMC6600209,,,"The mosquito-borne Zika virus (ZIKV) has been causing epidemic outbreaks on a global scale. Virus infection can result in severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Here, we characterized monoclonal antibodies isolated from a patient with an active Zika virus infection that potently neutralized virus infection in Vero cells at the nanogram-per-milliliter range. In addition, these antibodies enhanced internalization of virions into human leukemia K562 cells in vitro, indicating their possible ability to cause antibody-dependent enhancement of disease. Escape variants of the ZIKV MR766 strain to a potently neutralizing antibody, AC10, exhibited an amino acid substitution at residue S368 in the lateral ridge region of the envelope protein. Analysis of publicly availably ZIKV sequences revealed the S368 site to be conserved among the vast majority (97.6%) of circulating strains. We validated the importance of this residue by engineering a recombinant virus with an S368R point mutation that was unable to be fully neutralized by AC10. Four out of the 12 monoclonal antibodies tested were also unable to neutralize the virus with the S368R mutation, suggesting this region to be an important immunogenic epitope during human infection. Last, a time-of-addition infection assay further validated the escape variant and showed that all monoclonal antibodies inhibited virus binding to the cell surface. Thus, the present study demonstrates that the lateral ridge region of the envelope protein is likely an immunodominant, neutralizing epitope. IMPORTANCE Zika virus (ZIKV) is a global health threat causing severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Here, we analyzed the human monoclonal antibody response to acute ZIKV infection and found that neutralizing antibodies could not elicit Fc-mediated immune effector functions but could potentiate antibody-dependent enhancement of disease. We further identified critical epitopes involved with neutralization by generating and characterizing escape variants by whole-genome sequencing. We demonstrate that the lateral ridge region, particularly the S368 amino acid site, is critical for neutralization by domain III-specific antibodies.",,"['Bailey, Mark J.', 'Broecker, Felix', 'Freyn, Alec W.', 'Choi, Angela', 'Brown, Julia A.', 'Fedorova, Nadia', 'Simon, Viviana', 'Lim, Jean K.', 'Evans, Matthew J.', 'García-Sastre, Adolfo', 'Palese, Peter', 'Tan, Gene S.']",,,,
,PMC,"A Noncanonical Basic Motif of Epstein-Barr Virus ZEBRA Protein Facilitates Recognition of Methylated DNA, High-Affinity DNA Binding, and Lytic Activation",http://dx.doi.org/10.1128/JVI.00724-19,PMC6600195,,,"The pathogenesis of Epstein-Barr virus (EBV) infection, including development of lymphomas and carcinomas, is dependent on the ability of the virus to transit from latency to the lytic phase. This conversion, and ultimately disease development, depends on the molecular switch protein, ZEBRA, a viral bZIP transcription factor that initiates transcription from promoters of viral lytic genes. By binding to the origin of viral replication, ZEBRA is also an essential replication protein. Here, we identified a novel DNA-binding motif of ZEBRA, N terminal to the canonical bZIP domain. This RRTRK motif is important for high-affinity binding to DNA and is essential for recognizing the methylation state of viral promoters. Mutations in this motif lead to deficiencies in DNA binding, recognition of DNA methylation, lytic cycle DNA replication, and viral late gene expression. This work advances our understanding of ZEBRA-dependent activation of the viral lytic cascade. IMPORTANCE The binding of ZEBRA to methylated and unmethylated viral DNA triggers activation of the EBV lytic cycle, leading to viral replication and, in some patients, cancer development. Our work thoroughly examines how ZEBRA uses a previously unrecognized basic motif to bind nonmethylated and methylated DNA targets, leading to viral lytic activation. Our findings show that two different positively charged motifs, including the canonical BZIP domain and a newly identified RRTRK motif, contribute to the mechanism of DNA recognition by a viral AP-1 protein. This work contributes to the assessment of ZEBRA as a potential therapeutic target for antiviral and oncolytic treatments.",,"['Weber, Erin', 'Buzovetsky, Olga', 'Heston, Lee', 'Yu, Kuan-Ping', 'Knecht, Kirsten M.', 'El-Guindy, Ayman', 'Miller, George', 'Xiong, Yong']",,,,
,PMC,Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 1 Beta Interacts with Nucleoporin 62 To Promote Viral Replication and Immune Evasion,http://dx.doi.org/10.1128/JVI.00469-19,PMC6600190,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) blocks host mRNA nuclear export to the cytoplasm, and nonstructural protein 1 beta (nsp1β) of PRRSV has been identified as the protein that disintegrates the nuclear pore complex. In the present study, the molecular basis for the inhibition of host mRNA nuclear export was investigated. Nucleoporin 62 (Nup62) was found to bind to nsp1β, and the region representing the C-terminal residues 328 to 522 of Nup62 was determined to be the binding domain for nsp1β. The nsp1β L126A mutant in the SAP domain did not bind to Nup62, and in L126A-expressing cells, host mRNA nuclear export occurred normally. The vL126A mutant PRRSV generated by reverse genetics replicated at a lower rate, and the titer was lower than for wild-type virus. In nsp1β-overexpressing cells or small interfering RNA (siRNA)-mediated Nup62 knockdown cells, viral protein synthesis increased. Notably, the production of type I interferons (IFN-α/β), IFN-stimulated genes (PKR, OAS, Mx1, and ISG15 genes), IFN-induced proteins with tetratricopeptide repeats (IFITs) 1 and 2, and IFN regulatory factor 3 decreased in these cells. As a consequence, the growth of vL126A mutant PRRSV was rescued to the level of wild-type PRRSV. These findings are attributed to nuclear pore complex (NPC) disintegration by nsp1β, resulting in increased viral protein production and decreased host protein production, including antiviral proteins in the cytoplasm. Our study reveals a new strategy of PRRSV for immune evasion and enhanced replication during infection. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) causes PRRS and is known to effectively suppress host innate immunity. The PRRSV nsp1β protein blocks host mRNA nuclear export, which has been shown to be one of the viral mechanisms for inhibition of antiviral protein production. nsp1β binds to the cellular protein nucleoporin 62 (Nup62), and as a consequence, the nuclear pore complex (NPC) is disintegrated and the nucleocytoplasmic trafficking of host mRNAs and host proteins is blocked. We show the dual benefits of Nup62 and nsp1β binding for PRRSV replication: the inhibition of host antiviral protein expression and the exclusive use of host translation machinery by the virus. Our study unveils a novel strategy of PRRSV for immune evasion and enhanced replication during infection.",,"['Ke, Hanzhong', 'Han, Mingyuan', 'Kim, Jineui', 'Gustin, Kurt E.', 'Yoo, Dongwan']",,,,
,PMC,"Global health diplomacy, health and human security: The ascendancy of enlightened self-interest",http://dx.doi.org/10.4103/jehp.jehp_391_18,PMC6615119,31334259,CC BY-NC-SA,"The political, social, economic, and security implications of health-related issues such as emerging infectious diseases or the epidemic of Non Communicable Diseases offer a rare opportunity for professionals in foreign policy and international relations to engage with the health arena and at the same time for global health experts to enter into and intersect with the domain of diplomacy. The aim of this review is to understand and explore the concepts of global health diplomacy (GHD), health security, and human security. For this narrative review, a literature search was done in PubMed, Scopus, and EBSCO for the “global health diplomacy,” “health security,” and “human security,” and full-texts were reviewed. The recent outbreaks of Ebola in West Africa and Zika in South America are pertinent examples of the nature of the human security crisis and the imminent and severe threat posed to human life across the globe as a result of these epidemics. The Commission on Human Security defines human security as the protection of the vital core of all human lives from critical and pervasive threats. We highlight the ways in which health has now become an issue of national security/global concern and also how GHD can aid in the development of new bilateral or multilateral agreements to safeguard the health and security of people in our globalized world. The paper provides a prospective about, and overview of, health and human security that essentially emphasizes the growing interlinkages between global health, diplomacy, and foreign policy.",2019 Jun 27,"['Chattu, Vijay Kumar', 'Knight, Andy W', 'Kevany, Sebastian', 'Sehovic, Annamarie Bindenagel']",J Educ Health Promot,,,
,PMC,High basal heat-shock protein expression in bats confers resistance to cellular heat/oxidative stress,http://dx.doi.org/10.1007/s12192-019-01013-y,PMC6629734,,,"Bats, unique among mammals with powered flight, have many species with the longest size-proportionate lifespan of all mammals. Evolutionary adaptations would have been required to survive the elevated body temperatures during flight. Heat shock protein (HSP), highly conserved master regulators of cell stress, expression was examined across tissues and various cell lines in bats. Basal expression level of major HSPs (HSP70 and HSP90) is significantly higher in two different bat species compared to other mammals. This HSP expression could be a bat-unique, key factor to modulate cellular stress and death. Consequently, bat cells survive prolonged heat treatment, along with other stress stimuli, in a HSP-dependent manner, whereas other mammalian cells succumbed. This suggests HSP expression in bats could be an important adaption to intrinsic metabolic stresses like flight and therefore an important model to study stress resilience and longevity in general. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12192-019-01013-y) contains supplementary material, which is available to authorized users.",,"['Chionh, Yok Teng', 'Cui, Jie', 'Koh, Javier', 'Mendenhall, Ian H.', 'Ng, Justin H. J.', 'Low, Dolyce', 'Itahana, Koji', 'Irving, Aaron T.', 'Wang, Lin-Fa']",,,,
,PMC,Nipah and Hendra Virus Glycoproteins Induce Comparable Homologous but Distinct Heterologous Fusion Phenotypes,http://dx.doi.org/10.1128/JVI.00577-19,PMC6580972,,,"Nipah and Hendra viruses (NiV and HeV) exhibit high lethality in humans and are biosafety level 4 (BSL-4) paramyxoviruses in the growing genus Henipavirus. The attachment (G) and fusion (F) envelope glycoproteins are both required for viral entry into cells and for cell-cell fusion, which is pathognomonic of henipaviral infections. Here, we compared the fusogenic capacities between homologous and heterologous pairs of NiV and HeV glycoproteins. Importantly, to accurately measure their fusogenic capacities, as these depend on glycoprotein cell surface expression (CSE) levels, we inserted identical extracellular tags to both fusion (FLAG tags) or both attachment (hemagglutinin [HA] tags) glycoproteins. Importantly, these tags were placed in extracellular sites where they did not affect glycoprotein expression or function. NiV and HeV glycoproteins induced comparable levels of homologous HEK293T cell-cell fusion. Surprisingly, however, while the heterologous NiV F/HeV G (NF/HG) combination yielded a hypofusogenic phenotype, the heterologous HeV F/NiV G (HF/NG) combination yielded a hyperfusogenic phenotype. Pseudotyped viral entry levels primarily corroborated the fusogenic phenotypes of the glycoprotein pairs analyzed. Furthermore, we constructed G and F chimeras that allowed us to map the overall regions in G and F that contributed to these hyperfusogenic or hypofusogenic phenotypes. Importantly, the fusogenic phenotypes of the glycoprotein combinations negatively correlated with the avidities of F-G interactions, supporting the F/G dissociation model of henipavirus-induced membrane fusion, even in the context of heterologous glycoprotein pairs. IMPORTANCE The NiV and HeV henipaviruses are BSL-4 pathogens transmitted from bats. NiV and HeV often lead to human death and animal diseases. The formation of multinucleated cells (syncytia) is a hallmark of henipaviral infections and is caused by fusion of cells coordinated by interactions of the viral attachment (G) and fusion (F) glycoproteins. We found via various assays that viral entry and syncytium formation depend on the viral origin of the glycoproteins, with HeV F and NiV G promoting higher membrane fusion levels than their counterparts. This is important knowledge, since both viruses use the same bat vector species and potential coinfections of these or subsequent hosts may alter the outcome of disease.",,"['Bradel-Tretheway, Birgit G.', 'Zamora, J. Lizbeth Reyes', 'Stone, Jacquelyn A.', 'Liu, Qian', 'Li, Jenny', 'Aguilar, Hector C.']",,,,
,PMC,Aedes aegypti NeSt1 Protein Enhances Zika Virus Pathogenesis by Activating Neutrophils,http://dx.doi.org/10.1128/JVI.00395-19,PMC6580965,,,"Saliva from the mosquito vector of flaviviruses is capable of changing the local immune environment, leading to an increase in flavivirus-susceptible cells at the infected bite site. In addition, an antibody response to specific salivary gland (SG) components changes the pathogenesis of flaviviruses in human populations. To investigate whether antigenic SG proteins are capable of enhancing infection with Zika virus (ZIKV), a reemerging flavivirus primarily transmitted by the Aedes aegypti mosquito, we screened for antigenic SG proteins using a yeast display library and demonstrate that a previously undescribed SG protein we term neutrophil stimulating factor 1 (NeSt1) activates primary mouse neutrophils ex vivo. Passive immunization against NeSt1 decreases pro-interleukin-1β and CXCL2 expression, prevents macrophages from infiltrating the bite site, protects susceptible IFNAR(−/−) IFNGR(–/–) (AG129) mice from early ZIKV replication, and ameliorates virus-induced pathogenesis. These findings indicate that NeSt1 stimulates neutrophils at the mosquito bite site to change the immune microenvironment, allowing a higher level of early viral replication and enhancing ZIKV pathogenesis. IMPORTANCE When a Zika virus-infected mosquito bites a person, mosquito saliva is injected into the skin along with the virus. Molecules in this saliva can make virus infection more severe by changing the immune system to make the skin a better place for the virus to replicate. We identified a molecule that activates immune cells, called neutrophils, to recruit other immune cells, called macrophages, that the virus can infect. We named this molecule neutrophil-stimulating factor 1 (NeSt1). When we used antibodies to block NeSt1 in mice and then allowed Zika virus-infected mosquitoes to feed on these mice, they survived much better than mice that do not have antibodies against NeSt1. These findings give us more information about how mosquito saliva enhances virus infection, and it is possible that a vaccine against NeSt1 might protect people against severe Zika virus infection.",,"['Hastings, Andrew K.', 'Uraki, Ryuta', 'Gaitsch, Hallie', 'Dhaliwal, Khushwant', 'Stanley, Sydney', 'Sproch, Hannah', 'Williamson, Eric', 'MacNeil, Tyler', 'Marin-Lopez, Alejandro', 'Hwang, Jesse', 'Wang, Yuchen', 'Grover, Jonathan R.', 'Fikrig, Erol']",,,,
,PMC,A Genome-Wide Haploid Genetic Screen Identifies Heparan Sulfate-Associated Genes and the Macropinocytosis Modulator TMED10 as Factors Supporting Vaccinia Virus Infection,http://dx.doi.org/10.1128/JVI.02160-18,PMC6580964,,,"Vaccinia virus is a promising viral vaccine and gene delivery candidate and has historically been used as a model to study poxvirus-host cell interactions. We employed a genome-wide insertional mutagenesis approach in human haploid cells to identify host factors crucial for vaccinia virus infection. A library of mutagenized HAP1 cells was exposed to modified vaccinia virus Ankara (MVA). Deep-sequencing analysis of virus-resistant cells identified host factors involved in heparan sulfate synthesis, Golgi organization, and vesicular protein trafficking. We validated EXT1, TM9SF2, and TMED10 (TMP21/p23/p24δ) as important host factors for vaccinia virus infection. The critical roles of EXT1 in heparan sulfate synthesis and vaccinia virus infection were confirmed. TM9SF2 was validated as a player mediating heparan sulfate expression, explaining its contribution to vaccinia virus infection. In addition, TMED10 was found to be crucial for virus-induced plasma membrane blebbing and phosphatidylserine-induced macropinocytosis, presumably by regulating the cell surface expression of the TAM receptor Axl. IMPORTANCE Poxviruses are large DNA viruses that can infect a wide range of host species. A number of these viruses are clinically important to humans, including variola virus (smallpox) and vaccinia virus. Since the eradication of smallpox, zoonotic infections with monkeypox virus and cowpox virus are emerging. Additionally, poxviruses can be engineered to specifically target cancer cells and are used as a vaccine vector against tuberculosis, influenza, and coronaviruses. Poxviruses rely on host factors for most stages of their life cycle, including attachment to the cell and entry. These host factors are crucial for virus infectivity and host cell tropism. We used a genome-wide knockout library of host cells to identify host factors necessary for vaccinia virus infection. We confirm a dominant role for heparin sulfate in mediating virus attachment. Additionally, we show that TMED10, previously not implicated in virus infections, facilitates virus uptake by modulating the cellular response to phosphatidylserine.",,"['Luteijn, Rutger D.', 'van Diemen, Ferdy', 'Blomen, Vincent A.', 'Boer, Ingrid G. J.', 'Manikam Sadasivam, Saravanan', 'van Kuppevelt, Toin H.', 'Drexler, Ingo', 'Brummelkamp, Thijn R.', 'Lebbink, Robert Jan', 'Wiertz, Emmanuel J.']",,,,
,PMC,Carnivore Parvovirus Ecology in the Serengeti Ecosystem: Vaccine Strains Circulating and New Host Species Identified,http://dx.doi.org/10.1128/JVI.02220-18,PMC6580958,,,"Carnivore parvoviruses infect wild and domestic carnivores, and cross-species transmission is believed to occur. However, viral dynamics are not well understood, nor are the consequences for wild carnivore populations of the introduction of new strains into wild ecosystems. To clarify the ecology of these viruses in a multihost system such as the Serengeti ecosystem and identify potential threats for wildlife conservation, we analyzed, through real-time PCR, 152 samples belonging to 14 wild carnivore species and 62 samples from healthy domestic dogs. We detected parvovirus DNA in several wildlife tissues. Of the wild carnivore and domestic dog samples tested, 13% and 43%, respectively, were positive for carnivore parvovirus infection, but little evidence of transmission between the wild and domestic carnivores was detected. Instead, we describe two different epidemiological scenarios with separate routes of transmission: first, an endemic feline parvovirus (FPV) route of transmission maintained by wild carnivores inside the Serengeti National Park (SNP) and, second, a canine parvovirus (CPV) route of transmission among domestic dogs living around the periphery of the SNP. Twelve FPV sequences were characterized; new host-virus associations involving wild dogs, jackals, and hyenas were discovered; and our results suggest that mutations in the fragment of the vp2 gene were not required for infection of different carnivore species. In domestic dogs, 6 sequences belonged to the CPV-2a strain, while 11 belonged to the CPV-2 vaccine-derived strain. This is the first description of a vaccine-derived parvovirus strain being transmitted naturally. IMPORTANCE Carnivore parvoviruses are widespread among wild and domestic carnivores, which are vulnerable to severe disease under certain circumstances. This study furthers the understanding of carnivore parvovirus epidemiology, suggesting that feline parvoviruses are endemic in wild carnivores in the Serengeti National Park (SNP), with new host species identified, and that canine parvoviruses are present in the dog population living around the SNP. Little evidence of transmission of canine parvoviruses into wild carnivore species was found; however, the detection of vaccine-derived virus (described here for the first time to be circulating naturally in domestic dogs) highlights the importance of performing epidemiological research in the region.",,"['Calatayud, Olga', 'Esperón, Fernando', 'Cleaveland, Sarah', 'Biek, Roman', 'Keyyu, Julius', 'Eblate, Ernest', 'Neves, Elena', 'Lembo, Tiziana', 'Lankester, Felix']",,,,
,PMC,NAADP Receptors,http://dx.doi.org/10.1101/cshperspect.a035071,PMC6824237,,,"Of the established Ca(2+)-mobilizing messengers, NAADP is arguably the most tantalizing. It is the most potent, often efficacious at low nanomolar concentrations, and its receptors undergo dramatic desensitization. Recent studies have identified a new class of calcium-release channel, the two-pore channels (TPCs), as the likely targets for NAADP regulation, even though the effect may be indirect. These channels localized at endolysosomes, where they mediate local Ca(2+) release, and have highlighted a new role of acidic organelles as targets for messenger-evoked Ca(2+) mobilization. Three distinct roles of TPCs have been identified. The first is to effect local Ca(2+) release that may play a role in endolysosomal function including vesicular fusion and trafficking. The second is to trigger global calcium release by recruiting Ca(2+)-induced Ca(2+)-release (CICR) channels at lysosomal–endoplasmic reticulum (ER) junctions. The third is to regulate plasma membrane excitability by the targeting of Ca(2+) release from appropriately positioned subplasma membrane stores to regulate plasma membrane Ca(2+)-activated channels. In this review, I discuss the role of nicotinic acid adenine nucleotide diphosphate (NAADP)-mediated Ca(2+) release from endolysosomal stores as a widespread trigger for intracellular calcium signaling mechanisms, and how studies of TPCs are beginning to enhance our understanding of the central role of lysosomes in Ca(2+) signaling.",,"Galione, Antony",,,,
,PMC,"In vitro Antimicrobial Effects of Virus Block, Which Contains Multiple Polyoxometalate Compounds, and Hygienic Effects of Virus Block-Supplemented Moist Hand Towels",http://dx.doi.org/10.1159/000500897,PMC6604270,,,"BACKGROUND: Historical evidence has verified the multifaceted antiviral efficacy of polyoxometalates (PMs). METHODS: We carried out a study to investigate the antimicrobial effects of each of the 5 substances comprising virus block (VB): 3 PMs that have antibacterial and antiviral activity, an antibiotic agent, and an antibacterial agent. We also investigated the effectiveness of the addition of VB to moist hand towels in a study involving 120 volunteers. The time-dependent changes in metal ion concentrations in aqueous VB solution were analyzed using inductively coupled plasma atomic emission spectroscopy. RESULTS: The metal elements in the aqueous VB solution remained stable for 12 weeks without undergoing time-dependent changes. DISCUSSION: Further investigations were performed to study hand hygiene using moist hand towels in daily life settings. To this end, 120 volunteers provided 240 specimens that were used to investigate the presence of antibacterial compounds on the volunteers' hands before and after hand towel use. An aliquot of each specimen was suspended in phosphate-buffered saline and plated on agar media, and the number of colonies formed was counted. Normal bacterial flora found on the hands of the volunteers was investigated before and after the use of 4 different moist hand towels. CONCLUSIONS: The effects of VB and PMs were superior to those of commercial moist hand towels, indicating that effective data were obtained that may be useful for the practical application of the tested items.",,"['Dan, Katsuaki', 'Katoh, Naohiro', 'Matsuoka, Takaaki', 'Fujinami, Katsuyuki']",,,,
,PMC,Contagious Horror: Infectious Themes in Fiction and Film,http://dx.doi.org/10.3121/cmr.2019.1432,PMC6546279,,,"Infectious diseases have been a preeminent part of literature since the earliest human writings. In particular, they have contributed greatly to the genre of horror—written or visual art intended to startle or scare. Horror fiction has emphasized infectious themes from the earliest Babylonian and Hebrew texts. In medieval times, stories of vampires and werewolves often had a contagious component, and pivotal works of Victorian horror centered around fear of infection and contamination. As film became prominent in the 20th Century, a strong emphasis on themes of plague and apocalypse developed. An analysis of the use of infection in horror fiction and film shows that it often represents a metaphor for societal concerns, and it is extremely useful in framing challenging issues for a wide audience.",,"Sartin, Jeffrey S.",,,,
,PMC,Comprehensive Analysis of Severe Viral Infections of Respiratory Tract admitted to PICUs during the Winter Season in Turkey,http://dx.doi.org/10.5005/jp-journals-10071-23177,PMC6698354,31435144,CC BY,"OBJECTIVES: To analyze the course of seasonal viral infections of respiratory tract in patients hospitalized in pediatric intensive care units (PICU) of 16 centers in Turkey. MATERIALS AND METHODS: It is a retrospective, observational, and multicenter study conducted in 16 tertiary PICUs in Turkey includes a total of 302 children with viral cause in the nasal swab which required PICU admission with no interventions. RESULTS: Median age of patients was 12 months. Respiratory syncytial virus (RSV) was more common in patients over one year of age whereas influenza, human Bocavirus in patients above a year of age was more common (p <0.05). Clinical presentations influencing mortality were neurologic symptoms, tachycardia, hypoxia, hypotension, elevated lactate, and acidosis. The critical pH value related with mortality was ≤7.10, and critical PCO(2) ≥60 mm Hg. CONCLUSION: Our findings demonstrate that patients with neurological symptoms, tachycardia, hypoxia, hypotension, acidosis, impaired liver, and renal function at the time of admission exhibit more severe mortal progressions. Presence of acidosis and multiorgan failure was found to be predictor for mortality. Knowledge of clinical presentation and age-related variations among seasonal viruses may give a clue about severe course and prognosis. By presenting the analyzed data of 302 PICU admissions, current study reveals severity of viral respiratory tract infections and release tips for handling them. HOW TO CITE THIS ARTICLE: Kockuzu E, Bayrakcı B, Kesici S, Cıtak A, Karapınar K, Emeksiz S, et al. Comprehensive Analysis of Severe Viral Infections of Respiratory Tract admitted to PICUs During the Winter Season in Turkey. Indian J Crit Care Med 2019;23(6):263–269.",2019 Jun,"['Kockuzu, Esra', 'Bayrakcı, Benan', 'Kesici, Selman', 'Cıtak, Agop', 'Karapınar, Bulent', 'Emeksiz, Serhat', 'Anıl, Ayşe Berna', 'Kendirli, Tanıl', 'Yukselmis, Ufuk', 'Sevketoglu, Esra', 'Paksu, Şukru', 'Kutlu, Onur', 'Agın, Hasan', 'Yıldızdas, Dincer', 'Keskin, Halil', 'Kalkan, Gokhan', 'Hasanoglu, Arzu', 'Yazıcı, Mutlu Uysal', 'Sık, Guntulu', 'Kılınc, Arda', 'Durak, Fatih', 'Perk, Oktay', 'Talip, Mey', 'Yener, Nazik', 'Uzuner, Selcuk']",Indian J Crit Care Med,,,
,PMC,High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses,http://dx.doi.org/10.1128/JVI.00023-19,PMC6613765,,,"Coronaviruses (CoVs) act as cross-species viruses and have the potential to spread rapidly into new host species and cause epidemic diseases. Despite the severe public health threat of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome CoV (MERS-CoV), there are currently no drugs available for their treatment; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are urgently needed. To search for effective inhibitory agents, we performed high-throughput screening (HTS) of a 2,000-compound library of approved drugs and pharmacologically active compounds using the established genetically engineered human CoV OC43 (HCoV-OC43) strain expressing Renilla luciferase (rOC43-ns2Del-Rluc) and validated the inhibitors using multiple genetically distinct CoVs in vitro. We screened 56 hits from the HTS data and validated 36 compounds in vitro using wild-type HCoV-OC43. Furthermore, we identified seven compounds (lycorine, emetine, monensin sodium, mycophenolate mofetil, mycophenolic acid, phenazopyridine, and pyrvinium pamoate) as broad-spectrum inhibitors according to their strong inhibition of replication by four CoVs in vitro at low-micromolar concentrations. Additionally, we found that emetine blocked MERS-CoV entry according to pseudovirus entry assays and that lycorine protected BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This represents the first demonstration of in vivo real-time bioluminescence imaging to monitor the effect of lycorine on the spread and distribution of HCoV-OC43 in a mouse model. These results offer critical information supporting the development of an effective therapeutic strategy against CoV infection. IMPORTANCE Currently, there is no approved therapy to treat coronavirus infection; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are needed. Based on our high-throughput screening assay using a compound library, we identified seven compounds with broad-spectrum efficacy against the replication of four CoVs in vitro. Additionally, one compound (lycorine) was found to protect BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This inhibitor might offer promising therapeutic possibilities for combatting novel CoV infections in the future.",,"['Shen, Liang', 'Niu, Junwei', 'Wang, Chunhua', 'Huang, Baoying', 'Wang, Wenling', 'Zhu, Na', 'Deng, Yao', 'Wang, Huijuan', 'Ye, Fei', 'Cen, Shan', 'Tan, Wenjie']",,,,
,PMC,Articles of Significant Interest in This Issue,http://dx.doi.org/10.1128/JVI.00627-19,PMC6613763,,,,,,,,,
,PMC,Identification and Characterization of a Human Coronavirus 229E Nonstructural Protein 8-Associated RNA 3′-Terminal Adenylyltransferase Activity,http://dx.doi.org/10.1128/JVI.00291-19,PMC6613758,,,"Coronavirus nonstructural protein 8 (nsp8) has been suggested to have diverse activities, including noncanonical template-dependent polymerase activities. Here, we characterized a recombinant form of the human coronavirus 229E (HCoV-229E) nsp8 and found that the protein has metal ion-dependent RNA 3′-terminal adenylyltransferase (TATase) activity, while other nucleotides were not (or very inefficiently) transferred to the 3′ ends of single-stranded and (fully) double-stranded acceptor RNAs. Using partially double-stranded RNAs, very efficient TATase activity was observed if the opposite (template) strand contained a short 5′ oligo(U) sequence, while very little (if any) activity was detected for substrates with other homopolymeric or heteropolymeric sequences in the 5′ overhang. The oligo(U)-assisted/templated TATase activity on partial-duplex RNAs was confirmed for two other coronavirus nsp8 proteins, suggesting that the activity is conserved among coronaviruses. Replacement of a conserved Lys residue with Ala abolished the in vitro RNA-binding and TATase activities of nsp8 and caused a nonviable phenotype when the corresponding mutation was introduced into the HCoV-229E genome, confirming that these activities are mediated by nsp8 and critical for viral replication. In additional experiments, we obtained evidence that nsp8 has a pronounced specificity for adenylate and is unable to incorporate guanylate into RNA products, which strongly argues against the previously proposed template-dependent RNA polymerase activity of this protein. Given the presence of an oligo(U) stretch at the 5′ end of coronavirus minus-strand RNAs, it is tempting to speculate (but remains to be confirmed) that the nsp8-mediated TATase activity is involved in the 3′ polyadenylation of viral plus-strand RNAs. IMPORTANCE Previously, coronavirus nsp8 proteins were suggested to have template-dependent RNA polymerase activities resembling those of RNA primases or even canonical RNA-dependent RNA polymerases, while more recent studies have suggested an essential cofactor function of nsp8 (plus nsp7) for nsp12-mediated RNA-dependent RNA polymerase activity. In an effort to reconcile conflicting data from earlier studies, the study revisits coronavirus nsp8-associated activities using additional controls and proteins. The data obtained for three coronavirus nsp8 proteins provide evidence that the proteins share metal ion-dependent RNA 3′ polyadenylation activities that are greatly stimulated by a short oligo(U) stretch in the template strand. In contrast, nsp8 was found to be unable to select and incorporate appropriate (matching) nucleotides to produce cRNA products from heteropolymeric and other homooligomeric templates. While confirming the critical role of nsp8 in coronavirus replication, the study amends the list of activities mediated by coronavirus nsp8 proteins in the absence of other proteins.",,"['Tvarogová, Jana', 'Madhugiri, Ramakanth', 'Bylapudi, Ganesh', 'Ferguson, Lyndsey J.', 'Karl, Nadja', 'Ziebuhr, John']",,,,
,PMC,Analysis of Coronavirus Temperature-Sensitive Mutants Reveals an Interplay between the Macrodomain and Papain-Like Protease Impacting Replication and Pathogenesis,http://dx.doi.org/10.1128/JVI.02140-18,PMC6613754,,,"Analysis of temperature-sensitive (ts) mutant viruses is a classic method allowing researchers to identify genetic loci involved in viral replication and pathogenesis. Here, we report genetic analysis of a ts strain of mouse hepatitis virus (MHV), tsNC11, focusing on the role of mutations in the macrodomain (MAC) and the papain-like protease 2 (PLP2) domain of nonstructural protein 3 (nsp3), a component of the viral replication complex. Using MHV reverse genetics, we generated a series of mutant viruses to define the contributions of macrodomain- and PLP2-specific mutations to the ts phenotype. Viral replication kinetics and efficiency-of-plating analysis performed at permissive and nonpermissive temperatures revealed that changes in the macrodomain alone were both necessary and sufficient for the ts phenotype. Interestingly, mutations in the PLP2 domain were not responsible for the temperature sensitivity but did reduce the frequency of reversion of macrodomain mutants. Coimmunoprecipitation studies are consistent with an interaction between the macrodomain and PLP2. Expression studies of the macrodomain-PLP2 portion of nsp3 indicate that the ts mutations enhance proteasome-mediated degradation of the protein. Furthermore, we found that during virus infection, the replicase proteins containing the MAC and PLP2 mutations were more rapidly degraded at the nonpermissive temperature than were the wild-type proteins. Importantly, we show that the macrodomain and PLP2 mutant viruses trigger production of type I interferon in vitro and are attenuated in mice, further highlighting the importance of the macrodomain-PLP2 interplay in viral pathogenesis. IMPORTANCE Coronaviruses (CoVs) are emerging human and veterinary pathogens with pandemic potential. Despite the established and predicted threat these viruses pose to human health, there are currently no approved countermeasures to control infections with these viruses in humans. Viral macrodomains, enzymes that remove posttranslational ADP-ribosylation of proteins, and viral multifunctional papain-like proteases, enzymes that cleave polyproteins and remove polyubiquitin chains via deubiquitinating activity, are two important virulence factors. Here, we reveal an unanticipated interplay between the macrodomain and the PLP2 domain that is important for replication and antagonizing the host innate immune response. Targeting the interaction of these enzymes may provide new therapeutic opportunities to treat CoV disease.",,"['Deng, Xufang', 'Mettelman, Robert C.', 'O’Brien, Amornrat', 'Thompson, John A.', 'O’Brien, Timothy E.', 'Baker, Susan C.']",,,,
,PMC,C19ORF66 Broadly Escapes Virus-Induced Endonuclease Cleavage and Restricts Kaposi’s Sarcoma-Associated Herpesvirus,http://dx.doi.org/10.1128/JVI.00373-19,PMC6613750,,,"One striking characteristic of certain herpesviruses is their ability to induce rapid and widespread RNA decay in order to gain access to host resources. This phenotype is induced by viral endoribonucleases, including SOX in Kaposi’s sarcoma-associated herpesvirus (KSHV), muSOX in murine gammaherpesvirus 68 (MHV68), BGLF5 in Epstein-Barr virus (EBV), and vhs in herpes simplex virus 1 (HSV-1). Here, we performed comparative transcriptome sequencing (RNA-seq) upon expression of these herpesviral endonucleases in order to characterize their effect on the host transcriptome. Consistent with previous reports, we found that approximately two-thirds of transcripts were downregulated in cells expressing any of these viral endonucleases. Among the transcripts spared from degradation, we uncovered a cluster of transcripts that systematically escaped degradation from all tested endonucleases. Among these escapees, we identified C19ORF66 and reveal that this transcript is protected from degradation by its 3′ untranslated region (UTR). We then show that C19ORF66 is a potent KSHV restriction factor by impeding early viral gene expression, suggesting that its ability to escape viral cleavage may be an important component of the host response to viral infection. Collectively, our comparative approach is a powerful tool to pinpoint key regulators of the viral-host interplay and led us to uncover a novel KSHV regulator. IMPORTANCE Viruses are master regulators of the host gene expression machinery. This is crucial to promote viral infection and to dampen host immune responses. Many viruses, including herpesviruses, express RNases that reduce host gene expression through widespread mRNA decay. However, it emerged that some mRNAs escape this fate, although it has been difficult to determine whether these escaping transcripts benefit viral infection or instead participate in an antiviral mechanism. To tackle this question, we compared the effect of the herpesviral RNases on the human transcriptome and identified a cluster of transcripts consistently escaping degradation from all tested endonucleases. Among the protected mRNAs, we identified the transcript C19ORF66 and showed that it restricts Kaposi’s sarcoma-associated herpesvirus (KSHV) infection. Collectively, these results provide a framework to explore how the control of RNA fate in the context of viral-induced widespread mRNA degradation may influence the outcome of viral infection.",,"['Rodriguez, William', 'Srivastav, Kumaraman', 'Muller, Mandy']",,,,
,PMC,Arterivirus nsp4 Antagonizes Interferon Beta Production by Proteolytically Cleaving NEMO at Multiple Sites,http://dx.doi.org/10.1128/JVI.00385-19,PMC6613749,,,"Equine arteritis virus (EAV) and porcine reproductive and respiratory syndrome virus (PRRSV) represent two members of the family Arteriviridae and pose major threats for the horse- and swine-breeding industries worldwide. A previous study suggested that PRRSV nsp4, a 3C-like protease, antagonizes interferon beta (IFN-β) production by cleaving the NF-κB essential modulator (NEMO) at a single site, glutamate 349 (E349). Here, we demonstrated that EAV nsp4 also inhibited virus-induced IFN-β production by targeting NEMO for proteolytic cleavage and that the scission occurred at four sites: E166, E171, glutamine 205 (Q205), and E349. Additionally, we found that, besides the previously reported cleavage site E349 in NEMO, scission by PRRSV nsp4 took place at two additional sites, E166 and E171. These results imply that while cleaving NEMO is a common strategy utilized by EAV and PRRSV nsp4 to antagonize IFN induction, EAV nsp4 adopts a more complex substrate recognition mechanism to target NEMO. By analyzing the abilities of the eight different NEMO fragments resulting from EAV or PRRSV nsp4 scission to induce IFN-β production, we serendipitously found that a NEMO fragment (residues 1 to 349) could activate IFN-β transcription more robustly than full-length NEMO, whereas all other NEMO cleavage products were abrogated for the IFN-β-inducing capacity. Thus, NEMO cleavage at E349 alone may not be sufficient to completely inactivate the IFN response via this signaling adaptor. Altogether, our findings suggest that EAV and PRRSV nsp4 cleave NEMO at multiple sites and that this strategy is critical for disarming the innate immune response for viral survival. IMPORTANCE The arterivirus nsp4-encoded 3C-like protease (3CL(pro)) plays an important role in virus replication and immune evasion, making it an attractive target for antiviral therapeutics. Previous work suggested that PRRSV nsp4 suppresses type I IFN production by cleaving NEMO at a single site. In contrast, the present study demonstrates that both EAV and PRRSV nsp4 cleave NEMO at multiple sites and that this strategy is essential for disruption of type I IFN production. Moreover, we reveal that EAV nsp4 also cleaves NEMO at glutamine 205 (Q205), which is not targeted by PRRSV nsp4. Notably, targeting a glutamine in NEMO for cleavage has been observed only with picornavirus 3C proteases (3C(pro)) and coronavirus 3CL(pro). In aggregate, our work expands knowledge of the innate immune evasion mechanisms associated with NEMO cleavage by arterivirus nsp4 and describes a novel substrate recognition characteristic of EAV nsp4.",,"['Chen, Jiyao', 'Wang, Dang', 'Sun, Zheng', 'Gao, Li', 'Zhu, Xinyu', 'Guo, Jiahui', 'Xu, Shangen', 'Fang, Liurong', 'Li, Kui', 'Xiao, Shaobo']",,,,
,PMC,Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge,http://dx.doi.org/10.1126/scitranslmed.aau9242,PMC6732787,,,"Nipah virus is an emerging pathogen in the Paramyxoviridae family. Upon transmission of Nipah virus from its natural reservoir, Pteropus spp. fruit bats, to humans, it causes respiratory and neurological disease with a case-fatality rate about 70%. Human-to-human transmission has been observed during Nipah virus outbreaks in Bangladesh and India. A therapeutic treatment for Nipah virus disease is urgently needed. Here, we tested the efficacy of remdesivir (GS-5734), a broad-acting antiviral nucleotide prodrug, against Nipah virus Bangladesh genotype in African green monkeys. Animals were inoculated with a lethal dose of Nipah virus, and a once-daily intravenous remdesivir treatment was initiated 24 hours later and continued for 12 days. Mild respiratory signs were observed in two of four treated animals, whereas all control animals developed severe respiratory disease signs. In contrast to control animals, which all succumbed to the infection, all remsdesivir-treated animals survived the lethal challenge, indicating that remdesivir represents a promising antiviral treatment for Nipah virus infection.",,"['Lo, Michael K.', 'Feldmann, Friederike', 'Gary, Joy M.', 'Jordan, Robert', 'Bannister, Roy', 'Cronin, Jacqueline', 'Patel, Nishi R.', 'Klena, John D.', 'Nichol, Stuart T.', 'Cihlar, Tomas', 'Zaki, Sherif R.', 'Feldmann, Heinz', 'Spiropoulou, Christina F.', 'de Wit, Emmie']",,,,
,PMC,BCL6 modulates tissue neutrophil survival and exacerbates pulmonary inflammation following influenza virus infection,http://dx.doi.org/10.1073/pnas.1902310116,PMC6575592,,,"Neutrophils are vital for antimicrobial defense; however, their role during viral infection is less clear. Furthermore, the molecular regulation of neutrophil fate and function at the viral infected sites is largely elusive. Here we report that BCL6 deficiency in myeloid cells exhibited drastically enhanced host resistance to severe influenza A virus (IAV) infection. In contrast to the notion that BCL6 functions to suppress innate inflammation, we find that myeloid BCL6 deficiency diminished lung inflammation without affecting viral loads. Using a series of Cre-transgenic, reporter, and knockout mouse lines, we demonstrate that BCL6 deficiency in neutrophils, but not in monocytes or lung macrophages, attenuated host inflammation and morbidity following IAV infection. Mechanistically, BCL6 bound to the neutrophil gene loci involved in cellular apoptosis in cells specifically at the site of infection. As such, BCL6 disruption resulted in increased expression of apoptotic genes in neutrophils in the respiratory tract, but not in the circulation or bone marrow. Consequently, BCL6 deficiency promoted tissue neutrophil apoptosis. Partial neutrophil depletion led to diminished pulmonary inflammation and decreased host morbidity. Our results reveal a previously unappreciated role of BCL6 in modulating neutrophil apoptosis at the site of infection for the regulation of host disease development following viral infection. Furthermore, our studies indicate that tissue-specific regulation of neutrophil survival modulates host inflammation and tissue immunopathology during acute respiratory viral infection.",,"['Zhu, Bibo', 'Zhang, Ruixuan', 'Li, Chaofan', 'Jiang, Li', 'Xiang, Min', 'Ye, Zhenqing', 'Kita, Hirohito', 'Melnick, Ari M.', 'Dent, Alexander L.', 'Sun, Jie']",,,,
,PMC,Use of Big Data and Machine Learning Methods in the Monitoring and Evaluation of Digital Health Programs in India: An Exploratory Protocol,http://dx.doi.org/10.2196/11456,PMC6555122,31127716,CC BY,"BACKGROUND: Digital health programs, which encompass the subsectors of health information technology, mobile health, electronic health, telehealth, and telemedicine, have the potential to generate “big data.” OBJECTIVE: Our aim is to evaluate two digital health programs in India—the maternal mobile messaging service (Kilkari) and the mobile training resource for frontline health workers (Mobile Academy). We illustrate possible applications of machine learning for public health practitioners that can be applied to generate evidence on program effectiveness and improve implementation. Kilkari is an outbound service that delivers weekly gestational age–appropriate audio messages about pregnancy, childbirth, and childcare directly to families on their mobile phones, starting from the second trimester of pregnancy until the child is one year old. Mobile Academy is an Interactive Voice Response audio training course for accredited social health activists (ASHAs) in India. METHODS: Study participants include pregnant and postpartum women (Kilkari) as well as frontline health workers (Mobile Academy) across 13 states in India. Data elements are drawn from system-generated databases used in the routine implementation of programs to provide users with health information. We explain the structure and elements of the extracted data and the proposed process for their linkage. We then outline the various steps to be undertaken to evaluate and select final algorithms for identifying gaps in data quality, poor user performance, predictors for call receipt, user listening levels, and linkages between early listening and continued engagement. RESULTS: The project has obtained the necessary approvals for the use of data in accordance with global standards for handling personal data. The results are expected to be published in August/September 2019. CONCLUSIONS: Rigorous evaluations of digital health programs are limited, and few have included applications of machine learning. By describing the steps to be undertaken in the application of machine learning approaches to the analysis of routine system-generated data, we aim to demystify the use of machine learning not only in evaluating digital health education programs but in improving their performance. Where articles on analysis offer an explanation of the final model selected, here we aim to emphasize the process, thereby illustrating to program implementors and evaluators with limited exposure to machine learning its relevance and potential use within the context of broader program implementation and evaluation. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/11456",2019 May 24,"['Mohan, Diwakar', 'Bashingwa, Jean Juste Harrisson', 'Dane, Pierre', 'Chamberlain, Sara', 'Tiffin, Nicki', 'Lefevre, Amnesty']",JMIR Res Protoc,,,
,PMC,Exploring Australian Hajj Tour Operators’ Knowledge and Practices Regarding Pilgrims’ Health Risks: A Qualitative Study,http://dx.doi.org/10.2196/10960,PMC6552451,31124464,CC BY,"BACKGROUND: Travel agents are known to be one of the main sources of health information for pilgrims, and their advice is associated with positive health behaviors. OBJECTIVE: This study aimed to investigate travel agents’ health knowledge, what health advice they provide to the pilgrims, and their sources of health information. METHODS: In-depth interviews were conducted among specialist Hajj travel agents in Sydney, Australia. Thematic analysis was undertaken. RESULTS: Of the 13 accredited Hajj travel agents, 9 (69%) were interviewed. A high level of awareness regarding gastrointestinal infections, standard hygiene methods, and the risk of injury was noted among the participants and was included in advice provided to pilgrims. However, very limited knowledge and provision of advice about the risk of respiratory infections was identified. Knowledge of the compulsory meningococcal vaccine was high, and all participated travel agents reported influenza vaccine (a recommended vaccine) as a second “compulsory” vaccine for Hajj visas. Conversely, participants reported very limited knowledge about other recommended vaccines for Hajj. The Ministry of Hajj website and personal Hajj experience were the main sources of information. CONCLUSIONS: This study identifies a potential path for novel health promotion strategies to improve health knowledge among Hajj travel agents and subsequently among Hajj pilgrims.",2019 May 23,"['Alqahtani, Amani S', 'Tashani, Mohamed', 'Heywood, Anita E', 'Booy, Robert', 'Rashid, Harunor', 'Wiley, Kerrie E']",JMIR Public Health Surveill,,,
,PMC,A glycan shield on chimpanzee CD4 protects against infection by primate lentiviruses (HIV/SIV),http://dx.doi.org/10.1073/pnas.1813909116,PMC6561292,,,"Pandemic HIV-1 (group M) emerged following the cross-species transmission of a simian immunodeficiency virus from chimpanzees (SIVcpz) to humans. Primate lentiviruses (HIV/SIV) require the T cell receptor CD4 to enter into target cells. By surveying the sequence and function of CD4 in 50 chimpanzee individuals, we find that all chimpanzee CD4 alleles encode a fixed, chimpanzee-specific substitution (34T) that creates a glycosylation site on the virus binding surface of the CD4 receptor. Additionally, a single nucleotide polymorphism (SNP) has arisen in chimpanzee CD4 (68T) that creates a second glycosylation site on the same virus-binding interface. This substitution is not yet fixed, but instead alleles containing this SNP are still circulating within chimpanzee populations. Thus, all allelic versions of chimpanzee CD4 are singly glycosylated at the virus binding surface, and some allelic versions are doubly glycosylated. Doubly glycosylated forms of chimpanzee CD4 reduce HIV-1 and SIVcpz infection by as much as two orders of magnitude. Full restoration of virus infection in cells bearing chimpanzee CD4 requires reversion of both threonines at sites 34 and 68, destroying both of the glycosylation sites, suggesting that the effects of the glycans are additive. Differentially glycosylated CD4 receptors were biochemically purified and used in neutralization assays and microscale thermophoresis to show that the glycans on chimpanzee CD4 reduce binding affinity with the lentiviral surface glycoprotein, Env. These glycans create a shield that protects CD4 from being engaged by viruses, demonstrating a powerful form of host resistance against deadly primate lentiviruses.",,"['Warren, Cody J.', 'Meyerson, Nicholas R.', 'Stabell, Alex C.', 'Fattor, Will T.', 'Wilkerson, Gregory K.', 'Sawyer, Sara L.']",,,,
,PMC,Successful treatment of systemic lupus erythematosus pleuropericarditis with belimumab,http://dx.doi.org/10.5152/eurjrheum.2019.17169,PMC6668643,,,"Systemic lupus erythematosus (SLE) is characterized by a wide variety of manifestations and a difficult disease control in some patients. We present the case of a 51-year-old woman who presented with a flare of SLE including arthritis and pleuropericarditis that responded to neither leflunomide, methotrexate, nor high doses of prednisone. After initiating treatment with belimumab, the patient experienced a quick and notorious improvement. She remains stable to this day while continuing belimumab therapy.",,"['Carrión-Barberà, Irene', 'Salman-Monte, Tarek Carlos', 'Castell, Sonia', 'Castro-Domínguez, Francisco', 'Ojeda, Fabiola', 'Monfort, Jordi']",,,,
,PMC,MiR-27a-regulated FOXO1 promotes pancreatic ductal adenocarcinoma cell progression by enhancing Wnt/β-catenin signaling activity,,PMC6556653,,,"FOXO1, also known as FKHR, is a member of the Forkhead transcription factor family. Our previous study revealed that FOXO1 expression is significantly downregulated in pancreatic ductal adenocarcinoma (PDAC). However, our knowledge on the clinical significance of FOXO1 and its biological roles and associated mechanisms in PDAC tumorigenesis remains limited. In this study, we confirmed that FOXO1 is commonly downregulated in PDAC tissues, at both the mRNA and protein levels, compared to adjacent tissues. Furthermore, FOXO1 inhibited cell proliferation and tumor formation both in vitro and in vivo, and promoted pancreatic cancer cell invasion. Downregulation of FOXO1 resulted in enhanced Wnt/β-catenin signaling activity, thereby promoting cell proliferation and epithelial-mesenchymal transition. The highly expressed miR-27a could potentially be used to target the 3’-UTR of FOXO1 in PDAC tissues to inhibit or at least slow down the invasion and proliferation of cancerous cells. Taken together, our findings suggest that the miR-27a/FOXO1/β-catenin axis may serve as a promising therapeutic target in PDAC progression.",,"['Ling, Jing', 'Dong, Xiao', 'Wang, Lei', 'Xue, Ying', 'Jia, Xuebing', 'Song, Weifeng', 'Li, Qi']",,,,
,PMC,Antibody-Induced Internalization of HIV-1 Env Proteins Limits Surface Expression of the Closed Conformation of Env,http://dx.doi.org/10.1128/JVI.00293-19,PMC6532100,,,"To minimize immune responses against infected cells, HIV-1 limits the surface expression of its envelope glycoprotein (Env). Here, we demonstrate that this mechanism is specific for the Env conformation and affects the efficiency of antibody-dependent cellular cytotoxicity (ADCC). Using flow cytometry and confocal microscopy, we show that broadly neutralizing antibodies (bNAbs) targeting the “closed” conformation of Env induce its internalization from the surface. In contrast, non-neutralizing antibodies (nNAbs) are displayed on the cell surface for prolonged period of times. The bNAb-induced Env internalization can be decreased by blocking dynamin function, which translates into higher susceptibilities of infected cells to ADCC. Our results suggest that antibody-mediated Env internalization is a mechanism used by HIV-1 to evade immune responses against the “closed” conformation of Env expressed on HIV-1-infected cells. IMPORTANCE HIV-1 has evolved to acquire several strategies to limit the exposure of its envelope glycoproteins (Env) on the surface of infected cells. In this study, we show that antibody-induced Env internalization is conformation specific and reduces the susceptibility of infected cells to antibody-dependent cellular cytotoxicity (ADCC). Thus, a better understanding of this mechanism might help develop antibodies with improved capacities to mediate ADCC.",,"['Anand, Sai Priya', 'Grover, Jonathan R.', 'Tolbert, William D.', 'Prévost, Jérémie', 'Richard, Jonathan', 'Ding, Shilei', 'Baril, Sophie', 'Medjahed, Halima', 'Evans, David T.', 'Pazgier, Marzena', 'Mothes, Walther', 'Finzi, Andrés']",,,,
,PMC,The Infectious Bronchitis Coronavirus Envelope Protein Alters Golgi pH To Protect the Spike Protein and Promote the Release of Infectious Virus,http://dx.doi.org/10.1128/JVI.00015-19,PMC6532078,,,"Coronaviruses (CoVs) assemble by budding into the lumen of the early Golgi complex prior to exocytosis. The small CoV envelope (E) protein plays roles in assembly, virion release, and pathogenesis. CoV E has a single hydrophobic domain (HD), is targeted to Golgi membranes, and has cation channel activity in vitro. The E protein from avian infectious bronchitis virus (IBV) has dramatic effects on the secretory system, which require residues in the HD. Mutation of the HD of IBV E in a recombinant virus background results in impaired growth kinetics, impaired release of infectious virions, accumulation of IBV spike (S) protein on the plasma membrane compared to wild-type (WT) IBV-infected cells, and aberrant cleavage of IBV S on virions. We previously reported the formation of two distinct oligomeric pools of IBV E in transfected and infected cells. Disruption of the secretory pathway by IBV E correlates with a form that is likely monomeric, suggesting that the effects on the secretory pathway are independent of E ion channel activity. Here, we present evidence suggesting that the monomeric form of IBV E correlates with an increased Golgi luminal pH. Infection with IBV or expression of IBV E induces neutralization of Golgi pH, promoting a model in which IBV E alters the secretory pathway through interaction with host cell factors, protecting IBV S from premature cleavage and leading to the efficient release of infectious virus from the cells. This is the first demonstration of a coronavirus-induced alteration in the microenvironment of the secretory pathway. IMPORTANCE Coronaviruses are important human pathogens with significant zoonotic potential. Progress has been made toward identifying potential vaccine candidates for highly pathogenic human CoVs, including the use of attenuated viruses that lack the CoV E protein or express E mutants. However, no approved vaccines or antiviral therapeutics exist. Understanding the role of the CoV E protein in virus assembly and release is thus an important prerequisite for potential vaccines as well as in identifying novel antiviral therapeutics.",,"['Westerbeck, Jason W.', 'Machamer, Carolyn E.']",,,,
,PMC,Articles of Significant Interest in This Issue,http://dx.doi.org/10.1128/JVI.00552-19,PMC6532077,,,,,,,,,
,PMC,Identifying Protective Health Behaviors on Twitter: Observational Study of Travel Advisories and Zika Virus,http://dx.doi.org/10.2196/13090,PMC6535980,31094347,CC BY,"BACKGROUND: An estimated 3.9 billion individuals live in a location endemic for common mosquito-borne diseases. The emergence of Zika virus in South America in 2015 marked the largest known Zika outbreak and caused hundreds of thousands of infections. Internet data have shown promise in identifying human behaviors relevant for tracking and understanding other diseases. OBJECTIVE: Using Twitter posts regarding the 2015-16 Zika virus outbreak, we sought to identify and describe considerations and self-disclosures of a specific behavior change relevant to the spread of disease—travel cancellation. If this type of behavior is identifiable in Twitter, this approach may provide an additional source of data for disease modeling. METHODS: We combined keyword filtering and machine learning classification to identify first-person reactions to Zika in 29,386 English-language tweets in the context of travel, including considerations and reports of travel cancellation. We further explored demographic, network, and linguistic characteristics of users who change their behavior compared with control groups. RESULTS: We found differences in the demographics, social networks, and linguistic patterns of 1567 individuals identified as changing or considering changing travel behavior in response to Zika as compared with a control sample of Twitter users. We found significant differences between geographic areas in the United States, significantly more discussion by women than men, and some evidence of differences in levels of exposure to Zika-related information. CONCLUSIONS: Our findings have implications for informing the ways in which public health organizations communicate with the public on social media, and the findings contribute to our understanding of the ways in which the public perceives and acts on risks of emerging infectious diseases.",2019 May 13,"['Daughton, Ashlynn R', 'Paul, Michael J']",J Med Internet Res,,,
,PMC,A pilot study of minimum operational flow for loose-fitting powered air-purifying respirators used in healthcare cleaning services,http://dx.doi.org/10.1080/15459624.2019.1605241,PMC6720108,,,"The objective of this pilot study was to determine the minimum operational flow for loose-fitting powered air-purifying respirators (PAPR) used in healthcare cleaning services. An innovative respiratory flow recording device was worn by nine healthcare workers to obtain the minute volume (MV, L/min), mean inhalation flow (MIF, L/min), and peak inhalation flow (PIF, L/min) while performing “isolation unit work” (cleaning and disinfecting) of a patient room within 30 min. The MV and PIF were compared with the theoretical values obtained from an empirical formula. The correlations of MV, MIF, and PIF with subjects’ age, weight, height, body surface area (A(Du)), and body mass index (BMI) were analyzed. The average MV, MIF, and PIF were 33, 74, and 107 L/min, with maximal airflow rates of 41, 97, and 145 L/min, respectively, which are all below the current 170 L/min minimum operational flow for NIOSH certified loose-fitting PAPRs.",,"['Zhu, Jintuo', 'He, Xinjian', 'Bergman, Michael S.', 'Guffey, Steven', 'Nimbarte, Ashish D.', 'Zhuang, Ziqing']",,,,
,PMC,Structure and Peptidome of the Bat MHC Class I Molecule Reveal a Novel Mechanism Leading to High-Affinity Peptide Binding,http://dx.doi.org/10.4049/jimmunol.1900001,PMC6545463,,,"Bats are natural reservoir hosts, harboring more than 100 viruses, some of which are lethal to humans. The asymptomatic coexistence with viruses is thought to be connected to the unique immune system of bats. MHC class I (MHC I) presentation is closely related to cytotoxic lymphocyte immunity, which plays an important role in viral resistance. To investigate the characteristics of MHC I presentation in bats, the crystal structures of peptide–MHC I complexes of Pteropus alecto, Ptal-N*01:01/HEV-1 (DFANTFLP) and Ptal-N*01:01/HEV-2 (DYINTNLVP), and two related mutants, Ptal-N*01:01/HEV-1(PΩL) (DFANTFLL) and Ptal-N*01:01(ΔMDL)/HEV-1, were determined. Through structural analysis, we found that Ptal-N*01:01 had a multi-Ala–assembled pocket B and a flexible hydrophobic pocket F, which could accommodate variable anchor residues and allow Ptal-N*01:01 to bind numerous peptides. Three sequential amino acids, Met, Asp, and Leu, absent from the α1 domain of the H chain in other mammals, were present in this domain in the bat. Upon deleting these amino acids and determining the structure in p/Ptal-N*01:01(ΔMDL)/HEV-1, we found they helped form an extra salt-bridge chain between the H chain and the N-terminal aspartic acid of the peptide. By introducing an MHC I random peptide library for de novo liquid chromatography–tandem mass spectrometry analysis, we found that this insertion module, present in all types of bats, can promote MHC I presentation of peptides with high affinity during the peptide exchange process. This study will help us better understand how bat MHC I presents high-affinity peptides from an extensive binding peptidome and provides a foundation to understand the cellular immunity of bats.",,"['Qu, Zehui', 'Li, Zibin', 'Ma, Lizhen', 'Wei, Xiaohui', 'Zhang, Lijie', 'Liang, Ruiying', 'Meng, Geng', 'Zhang, Nianzhi', 'Xia, Chun']",,,,
,PMC,Further Defining the Human Virome using NGS: Identification of Redondoviridae,http://dx.doi.org/10.1016/j.chom.2019.04.010,PMC6849504,,,"In this issue of Cell Host & Microbe, Abbas et al. (2019) uncover a previously undefined family of single-stranded DNA viruses, Redondoviridae, in human ororespiratory sites. The presence of Redondoviridae associates with critical illness such as respiratory failure and periodontitis, illustrating the power of metagenomics to define the human virome.",,"['Noell, Kristin', 'Kolls, Jay K.']",,,,
,PMC,Risk assessment strategies for early detection and prediction of infectious disease outbreaks associated with climate change,http://dx.doi.org/10.14745/ccdr.v45i05a02,PMC6587687,,,"A new generation of surveillance strategies is being developed to help detect emerging infections and to identify the increased risks of infectious disease outbreaks that are expected to occur with climate change. These surveillance strategies include event-based surveillance (EBS) systems and risk modelling. The EBS systems use open-source internet data, such as media reports, official reports, and social media (such as Twitter) to detect evidence of an emerging threat, and can be used in conjunction with conventional surveillance systems to enhance early warning of public health threats. More recently, EBS systems include artificial intelligence applications such machine learning and natural language processing to increase the speed, capacity and accuracy of filtering, classifying and analysing health-related internet data. Risk modelling uses statistical and mathematical methods to assess the severity of disease emergence and spread given factors about the host (e.g. number of reported cases), pathogen (e.g. pathogenicity) and environment (e.g. climate suitability for reservoir populations). The types of data in these models are expanding to include health-related information from open-source internet data and information on mobility patterns of humans and goods. This information is helping to identify susceptible populations and predict the pathways from which infections might spread into new areas and new countries. As a powerful addition to traditional surveillance strategies that identify what has already happened, it is anticipated that EBS systems and risk modelling will increasingly be used to inform public health actions to prevent, detect and mitigate the climate change increases in infectious diseases.",,"['Rees, EE', 'Ng, V', 'Gachon, P', 'Mawudeku, A', 'McKenney, D', 'Pedlar, J', 'Yemshanov, D', 'Parmely, J', 'Knox, J']",,,,
,PMC,Essential Role of Enterovirus 2A Protease in Counteracting Stress Granule Formation and the Induction of Type I Interferon,http://dx.doi.org/10.1128/JVI.00222-19,PMC6498061,,,"Most viruses have acquired mechanisms to suppress antiviral alpha/beta interferon (IFN-α/β) and stress responses. Enteroviruses (EVs) actively counteract the induction of IFN-α/β gene transcription and stress granule (SG) formation, which are increasingly implicated as a platform for antiviral signaling, but the underlying mechanisms remain poorly understood. Both viral proteases (2A(pro) and 3C(pro)) have been implicated in the suppression of these responses, but these conclusions predominantly rely on ectopic overexpression of viral proteases or addition of purified viral proteases to cell lysates. Here, we present a detailed and comprehensive comparison of the effect of individual enterovirus proteases on the formation of SGs and the induction of IFN-α/β gene expression in infected cells for representative members of the enterovirus species EV-A to EV-D. First, we show that SG formation and IFN-β induction are suppressed in cells infected with EV-A71, coxsackie B3 virus (CV-B3), CV-A21, and EV-D68. By introducing genes encoding CV-B3 proteases in a recombinant encephalomyocarditis virus (EMCV) that was designed to efficiently activate antiviral responses, we show that CV-B3 2A(pro), but not 3C(pro), is the major antagonist that counters SG formation and IFN-β gene transcription and that 2A(pro)’s proteolytic activity is essential for both functions. 2A(pro) efficiently suppressed SG formation despite protein kinase R (PKR) activation and α subunit of eukaryotic translation initiation factor 2 phosphorylation, suggesting that 2A(pro) antagonizes SG assembly or promotes its disassembly. Finally, we show that the ability to suppress SG formation and IFN-β gene transcription is conserved in the 2A(pro) of EV-A71, CV-A21, and EV-D68. Collectively, our results indicate that enterovirus 2A(pro) plays a key role in inhibiting innate antiviral cellular responses. IMPORTANCE Enteroviruses are important pathogens that can cause a variety of diseases in humans, including aseptic meningitis, myocarditis, hand-foot-and-mouth disease, conjunctivitis, and acute flaccid paralysis. Like many other viruses, enteroviruses must counteract antiviral cellular responses to establish an infection. It has been suggested that enterovirus proteases cleave cellular factors to perturb antiviral pathways, but the exact contribution of viral proteases 2A(pro) and 3C(pro) remains elusive. Here, we show that 2A(pro), but not 3C(pro), of all four human EV species (EV-A to EV-D) inhibits SG formation and IFN-β gene transcription. Our observations suggest that enterovirus 2A(pro) has a conserved function in counteracting antiviral host responses and thereby is the main enterovirus “security protein.” Understanding the molecular mechanisms of enterovirus immune evasion strategies may help to develop countermeasures to control infections with these viruses.",,"['Visser, Linda J.', 'Langereis, Martijn A.', 'Rabouw, Huib H.', 'Wahedi, Maryam', 'Muntjewerff, Elke M.', 'de Groot, Raoul J.', 'van Kuppeveld, Frank J. M.']",,,,
,PMC,Articles of Significant Interest in This Issue,http://dx.doi.org/10.1128/JVI.00485-19,PMC6498047,,,,,,,,,
,PMC,Neuroinflammation During RNA Viral Infections,http://dx.doi.org/10.1146/annurev-immunol-042718-041417,PMC6731125,,,"Neurotropic RNA viruses continue to emerge and are increasingly linked to diseases of the central nervous system (CNS) despite viral clearance. Indeed, the overall mortality of viral encephalitis in immunocompetent individuals is low, suggesting efficient mechanisms of virologic control within the CNS. Both immune and neural cells participate in this process, which requires extensive innate immune signaling between resident and infiltrating cells, including microglia and monocytes, that regulate the effector functions of antiviral T and B cells as they gain access to CNS compartments. While these interactions promote viral clearance via mainly neuroprotective mechanisms, they may also promote neuropathology and, in some cases, induce persistent alterations in CNS physiology and function that manifest as neurologic and psychiatric diseases. This review discusses mechanisms of RNA virus clearance and neurotoxicity during viral encephalitis with a focus on the cytokines essential for immune and neural cell inflammatory responses and interactions. Understanding neuroimmune communications in the setting of viral infections is essential for the development of treatments that augment neuroprotective processes while limiting ongoing immunopathological processes that cause ongoing CNS disease.",,"['Klein, Robyn S.', 'Garber, Charise', 'Funk, Kristen E.', 'Salimi, Hamid', 'Soung, Allison', 'Kanmogne, Marlene', 'Manivasagam, Sindhu', 'Agner, Shannon', 'Cain, Matthew']",,,,
,PMC,Evaluation of the Aries Bordetella Assay for Detection and Identification of Bordetella pertussis in Nasopharyngeal Swab Specimens,http://dx.doi.org/10.1128/JCM.01966-18,PMC6498007,,,"The Aries Bordetella assay (Aries BA) (Luminex Corporation) recently received FDA clearance for the detection and differentiation of Bordetella pertussis and Bordetella parapertussis nucleic acids in nasopharyngeal swab (NPS) samples. The objective of this study was to evaluate the performance of the Aries BA in comparison to that of the BioFire FilmArray respiratory panel (RP). The Aries BA was evaluated using retrospective, remnant nasopharyngeal swabs (NPS), previously tested by FilmArray RP. Performance characteristics evaluated included positive percent agreement (PPA) and negative percent agreement (NPA) with the FilmArray RP. Discordant analysis was performed using bidirectional sequencing. A time and motion study was performed to compare the laboratory workflow of the two tests. Three hundred samples were included in the study. There were no samples positive for B. parapertussis. The PPA and NPA of the Aries BA were 61.1% (95% confidence interval [CI], 35.8 to 82.7%) and 100% (95% CI, 98.7 to 100%). Discordant results included five Bordetella bronchiseptica results that were incorrectly identified as B. pertussis by the FilmArray RP and one false-negative result for both the Aries BA and the FilmArray RP. The overall agreement between the Aries BA and FilmArray RP for the detection of B. pertussis was considered good at 97.7% with a kappa value of 0.71 (95% CI, 0.51 to 0.9). The Aries BA offers a new diagnostic option for the rapid and targeted approach to the diagnosis of pertussis. Unlike the FilmArray RP, the Aries BA did not cross-react with B. bronchiseptica in our study, although a larger sample set should be tested to confirm this finding.",,"['McMillen, T.', 'Chow, H. Y.', 'Das, Shubhagata', 'Dunbar, Sherry A.', 'Babady, N. E.']",,,,
,PMC,Introducing a New Algorithm for Classification of Etiology in Studies on Pediatric Pneumonia: Protocol for the Trial of Respiratory Infections in Children for Enhanced Diagnostics Study,http://dx.doi.org/10.2196/12705,PMC6658235,31025954,CC BY,"BACKGROUND: There is a need to better distinguish viral infections from antibiotic-requiring bacterial infections in children presenting with clinical community-acquired pneumonia (CAP) to assist health care workers in decision making and to improve the rational use of antibiotics. OBJECTIVE: The overall aim of the Trial of Respiratory infections in children for ENhanced Diagnostics (TREND) study is to improve the differential diagnosis of bacterial and viral etiologies in children aged below 5 years with clinical CAP, by evaluating myxovirus resistance protein A (MxA) as a biomarker for viral CAP and by evaluating an existing (multianalyte point-of-care antigen detection test system [mariPOC respi] ArcDia International Oy Ltd.) and a potential future point-of-care test for respiratory pathogens. METHODS: Children aged 1 to 59 months with clinical CAP as well as healthy, hospital-based, asymptomatic controls will be included at a pediatric emergency hospital in Stockholm, Sweden. Blood (analyzed for MxA and C-reactive protein) and nasopharyngeal samples (analyzed with real-time polymerase chain reaction as the gold standard and antigen-based mariPOC respi test as well as saved for future analyses of a novel recombinase polymerase amplification–based point-of-care test for respiratory pathogens) will be collected. A newly developed algorithm for the classification of CAP etiology will be used as the reference standard. RESULTS: A pilot study was performed from June to August 2017. The enrollment of study subjects started in November 2017. Results are expected by the end of 2019. CONCLUSIONS: The findings from the TREND study can be an important step to improve the management of children with clinical CAP. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12705",2019 Apr 26,"['Rhedin, Samuel Arthur', 'Eklundh, Annika', 'Ryd-Rinder, Malin', 'Naucler, Pontus', 'Mårtensson, Andreas', 'Gantelius, Jesper', 'Zenk, Ingela', 'Andersson-Svahn, Helene', 'Nybond, Susanna', 'Rasti, Reza', 'Lindh, Magnus', 'Andersson, Maria', 'Peltola, Ville', 'Waris, Matti', 'Alfvén, Tobias']",JMIR Res Protoc,,,
,PMC,Enterovirus type 71-immunized chicken egg yolk immunoglobulin has cross antiviral activity against coxsackievirus A16 in vitro,http://dx.doi.org/10.3892/etm.2019.7529,PMC6566110,,,"To exploit a cross passive immunotherapy for enterovirus-induced hand-foot-and-mouth disease (HFMD), the cross antiviral activity of a neutralizing antibody against enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) was investigated in vitro. White Leghorn specific-pathogen-free chickens were immunized with EV71 antigens and a specific isolated immunoglobulin (IgY) was prepared from the chicken egg yolk. IgY was further purified and characterized by SDS-PAGE, ELISA, western blotting and bidirectional immune agar diffusion testing. The antiviral activity and dose-response of the IgY were determined by assessing the cytopathic effect in rhabdomyosarcoma (RD) cells in vitro. It was indicated that the levels of IgY were increased at day 7, peaked at week 7 and were maintained at a higher level for 4 weeks following immunization when compared with the negative control. The results of western blotting and bidirectional immune agar diffusion testing revealed that the IgY had cross-binding properties in EV71 and CVA16 strains through targeting the envelope proteins (VP0, VP1 and VP3) of EV71 and CVA16. Neutralization assay results indicated that the infectivity of EV71 and CVA16 strains in RD cells was cross-blocked by IgY in a dose-dependent manner. To conclude, these findings indicate that IgY has cross antiviral activity against EV71 and CVA16 in vitro, and could potentially be developed as a passive immunotherapy for EV71- and CVA16-induced HFMD.",,"['Gao, Enyi', 'Wu, Shuwen', 'Xu, Qing', 'Zeng, Yonglian', 'Tan, Ning', 'He, Songqing', 'Yang, Yang', 'Wei, Jingchen']",,,,
,PMC,Sub- or supercritical transmissibilities in a finite disease outbreak: Symmetry in outbreak properties of a disease conditioned on extinction,http://dx.doi.org/10.1016/j.jtbi.2019.01.033,PMC6408326,30711456,CC BY,"This work is concerned with the transmissibility of a disease, on observation of an outbreak of limited size. When such an outbreak occurs, an accurate estimate of the transmissibility of the responsible pathogen is essential for an appropriate response to future outbreaks. Transmissibility is usually characterised in terms of the reproduction number, R, which is the mean number of new cases of infection produced by a single infectious individual. A subcritical reproduction number (R < 1) guarantees that an outbreak will eventually die out of its own accord. By contrast, a supercritical reproduction number (R > 1) does not guarantee spread of the disease, since even with appreciable transmissibility, an outbreak may become extinct due to stochastic effects associated with a small number of infected individuals. Once the number of infectious individuals is conditioned on extinction, we show that an exact symmetry of the underlying theory ensures two distinct values of R, one larger than unity, the other smaller than unity, for which all outbreak properties are identical, with no signature of difference. Therefore a disease with a subcritical R, or its supercritical counterpart, when conditioned on extinction, have, for a given outbreak, identical individual likelihoods. In the full likelihood, this symmetry is lost, since the individual likelihood for a subcritical R is weighted by an extinction probability of unity, but the individual likelihood of a supercritical R is weighted by a sub-unity extinction probability. However, the inference can still benefit from the underlying symmetry, since it yields a mapping of all supercritical reproduction numbers onto the subcritical domain (R < 1), thereby speeding up evaluation of the likelihood profile. The symmetry holds in the standard situation, where the distribution of secondary cases is Poisson, as well as where this distribution has a negative binomial form and super-spreading can occur.",2019 Apr 21,"['Waxman, David', 'Nouvellet, Pierre']",J Theor Biol,,,
,PMC,OAS1 gene polymorphism is associated with central nervous system involvement in children with enterovirus 71 infection,http://dx.doi.org/10.12122/j.issn.1673-4254.2019.04.01,PMC6744003,,,"OBJECTIVE: We investigated the association between OAS1 gene polymorphism and susceptibility to central nervous system (CNS) involvement of enterovirus (EV)71 infection. METHODS: This case-control study was conducted among 180 children with EV71 infection, including 72 with mild infections without any complications and 108 with severe infections and CNS involvement; 201 children undergoing routine physical examination served as the healthy controls. For all the participants, the single nucleotide polymorphisms (SNPs) at OAS1 rs2660 and rs1131454 were analyzed using SNPscan multiple SNP typing methods. RESULTS: No significant differences were found between the case and control groups in genotype or allele distributions of rs2660 and rs1131454. OAS1 rs2660 polymorphism was significantly different between the children with CNS involvement and those with mild EV71 infection, and the genotype AG frequency was higher and the genotype GG frequency was lower in children with CNS involvement. No significant difference was found in the distribution of genotypes or alleles of rs1131454 between the children with CNS involvement and those with mild EV71 infection. CONCLUSION: OAS1 gene rs2660 and rs1131454 SNPs are not associated with the susceptibility to or CNS involvement of EV71 infection, but OAS1 rs2660 SNPs are significantly correlated with the susceptibility to CNS involvement in EV71 infection. Children carrying OAS1 rs2660 AG genotype are more likely to have CNS involvement after EV71 infection.",,"[None, None, None, None, None, None, None]",,,,
,PMC,Toxoflavin Produced by Burkholderia gladioli from Lycoris aurea Is a New Broad-Spectrum Fungicide,http://dx.doi.org/10.1128/AEM.00106-19,PMC6495751,,,"Fungal infections not only cause extensive agricultural damage but also result in serious diseases in the immunodeficient populations of human beings. Moreover, the increasing emergence of drug resistance has led to a decrease in the efficacy of current antifungals. Thus, screening of new antifungal agents is imperative in the fight against antifungal drug resistance. In this study, we show that an endophytic bacterium, Burkholderia gladioli HDXY-02, isolated from the medicinal plant Lycoris aurea, showed broad-spectrum antifungal activity against plant and human fungal pathogens. An antifungal ability assay indicated that the bioactive component was produced from strain HDXY-02 having an extracellular secreted component with a molecular weight lower than 1,000 Da. In addition, we found that this new antifungal could be produced effectively by liquid fermentation of HDXY-02. Furthermore, the purified component contributing to the antifungal activity was identified to be toxoflavin, a yellow compound possessing a pyrimido[5,4-e][1,2,4]triazine ring. In vitro bioactivity studies demonstrated that purified toxoflavin from B. gladioli HDXY-02 cultures had a significant antifungal activity against the human fungal pathogen Aspergillus fumigatus, resulting in abolished germination of conidia. More importantly, the growth inhibition by toxoflavin was observed in both wild-type and drug-resistant mutants (cyp51A and non-cyp51A) of A. fumigatus. Finally, an optimized protocol for the large-scale production of toxoflavin (1,533 mg/liter) has been developed. Taken together, our findings provide a promising biosynthetic resource for producing a new antifungal reagent, toxoflavin, from isolates of the endophytic bacterium B. gladioli. IMPORTANCE Human fungal infections are a growing problem associated with increased morbidity and mortality. Moreover, a growing number of antifungal-resistant fungal isolates have been reported over the past decade. Thus, the need for novel antifungal agents is imperative. In this study, we show that an endophytic bacterium, Burkholderia gladioli, isolated from the medicinal plant Lycoris aurea, is able to abundantly secrete a compound, toxoflavin, which has a strong fungicidal activity not only against plant fungal pathogens but also against human fungal pathogens Aspergillus fumigatus and Candida albicans, Cryptococcus neoformans, and the model filamentous fungus Aspergillus nidulans. More importantly, toxoflavin also displays an efficacious inhibitory effect against azole antifungal-resistant mutants of A. fumigatus. Consequently, our findings provide a promising approach to abundantly produce toxoflavin, which has novel broad-spectrum antifungal activity, especially against those currently problematic drug-resistant isolates.",,"['Li, Xiaodan', 'Li, Yikui', 'Wang, Ren', 'Wang, Qizhi', 'Lu, Ling']",,,,
,PMC,DNA-encoded bispecific T cell engagers and antibodies present long-term antitumor activity,http://dx.doi.org/10.1172/jci.insight.126086,PMC6538381,,,"Specific antibody therapy, including mAbs and bispecific T cell engagers (BiTEs), are important new tools for cancer immunotherapy. However, these approaches are slow to develop and may be limited in their production, thus restricting the patients who can access these treatments. BiTEs exhibit a particularly short half-life and difficult production. The development of an approach allowing simplified development, delivery, and in vivo production would be an important advance. Here we describe the development of a designed synthetic DNA plasmid, which we optimized to permit high expression of an anti-HER2 antibody (HER2dMAb) and delivered it into animals through adaptive electroporation. HER2dMAb was efficiently expressed in vitro and in vivo, reaching levels of 50 μg/ml in mouse sera. Mechanistically, HER2dMAb blocked HER2 signaling and induced antibody-dependent cytotoxicity. HER2dMAb delayed tumor progression for HER2-expressing ovarian and breast cancer models. We next used the HER2dMAb single-chain variable fragment portion to engineer a DNA-encoded BiTE (DBiTE). This HER2DBiTE was expressed in vivo for approximately 4 months after a single administration. The HER2DBiTE was highly cytolytic and delayed cancer progression in mice. These studies illustrate an approach to generate DBiTEs in vivo, which represent promising immunotherapies for HER2(+) tumors, including ovarian and potentially other cancers.",,"['Perales-Puchalt, Alfredo', 'Duperret, Elizabeth K.', 'Yang, Xue', 'Hernandez, Patricia', 'Wojtak, Krzysztof', 'Zhu, Xizhou', 'Jung, Seang-Hwan', 'Tello-Ruiz, Edgar', 'Wise, Megan C.', 'Montaner, Luis J.', 'Muthumani, Kar', 'Weiner, David B.']",,,,
,PMC,Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1,http://dx.doi.org/10.1056/NEJMoa1815408,PMC6636624,,,"BACKGROUND: Allogeneic hematopoietic stem-cell transplantation for X-linked severe combined immunodeficiency (SCID-X1) often fails to reconstitute immunity associated with T cells, B cells, and natural killer (NK) cells when matched sibling donors are unavailable unless high-dose chemotherapy is given. In previous studies, autologous gene therapy with γ-retroviral vectors failed to reconstitute B-cell and NK-cell immunity and was complicated by vector-related leukemia. METHODS: We performed a dual-center, phase 1–2 safety and efficacy study of a lentiviral vector to transfer IL2RG complementary DNA to bone marrow stem cells after low-exposure, targeted busulfan conditioning in eight infants with newly diagnosed SCID-X1. RESULTS: Eight infants with SCID-X1 were followed for a median of 16.4 months. Bone marrow harvest, busulfan conditioning, and cell infusion had no unexpected side effects. In seven infants, the numbers of CD3+, CD4+, and naive CD4+ T cells and NK cells normalized by 3 to 4 months after infusion and were accompanied by vector marking in T cells, B cells, NK cells, myeloid cells, and bone marrow progenitors. The eighth infant had an insufficient T-cell count initially, but T cells developed in this infant after a boost of gene-corrected cells without busulfan conditioning. Previous infections cleared in all infants, and all continued to grow normally. IgM levels normalized in seven of the eight infants, of whom four discontinued intravenous immune globulin supplementation; three of these four in-fants had a response to vaccines. Vector insertion-site analysis was performed in seven infants and showed polyclonal patterns without clonal dominance in all seven. CONCLUSIONS: Lentiviral vector gene therapy combined with low-exposure, targeted busulfan conditioning in infants with newly diagnosed SCID-X1 had low-grade acute toxic effects and resulted in multilineage engraftment of transduced cells, reconstitution of functional T cells and B cells, and normalization of NK-cell counts during a median follow-up of 16 months. (Funded by the American Lebanese Syrian Associated Charities and others; LVXSCID-ND ClinicalTrials.gov number, NCT01512888.)",,"['Mamcarz, E.', 'Zhou, S.', 'Lockey, T.', 'Abdelsamed, H.', 'Cross, S.J.', 'Kang, G.', 'Ma, Z.', 'Condori, J.', 'Dowdy, J.', 'Triplett, B.', 'Li, C.', 'Maron, G.', 'Aldave Becerra, J.C.', 'Church, J.A.', 'Dokmeci, E.', 'Love, J.T.', 'Ain, A.C. da Matta', 'van der Watt, H.', 'Tang, X.', 'Janssen, W.', 'Ryu, B.Y.', 'De Ravin, S.S.', 'Weiss, M.J.', 'Youngblood, B.', 'Long‑Boyle, J.R.', 'Gottschalk, S.', 'Meagher, M.M.', 'Malech, H.L.', 'Puck, J.M.', 'Cowan, M.J.', 'Sorrentino, B.P.']",,,,
,PMC,Structural insights into RNA recognition by the Chikungunya virus nsP2 helicase,http://dx.doi.org/10.1073/pnas.1900656116,PMC6511008,,,"Chikungunya virus (CHIKV) is transmitted to humans through mosquitoes and causes Chikungunya fever. Nonstructural protein 2 (nsP2) exhibits the protease and RNA helicase activities that are required for viral RNA replication and transcription. Unlike for the C-terminal protease, the structure of the N-terminal RNA helicase (nsP2h) has not been determined. Here, we report the crystal structure of the nsP2h bound to the conserved 3′-end 14 nucleotides of the CHIKV genome and the nonhydrolyzable transition-state nucleotide analog ADP-AlF(4). Overall, the structural analysis revealed that nsP2h adopts a uniquely folded N-terminal domain followed by a superfamily 1 RNA helicase fold. The conserved helicase motifs establish polar contacts with the RNA backbone. There are three hydrophobic residues (Y161, F164, and F287) which form stacking interactions with RNA bases and thereby bend the RNA backbone. An F287A substitution that disrupted these stacking interactions increased the basal ATPase activity but decreased the RNA binding affinity. Furthermore, the F287A substitution reduced viral infectivity by attenuating subgenomic RNA synthesis. Replication of the mutant virus was restored by pseudoreversion (A287V) or adaptive mutations in the RecA2 helicase domain (T358S or V410I). Y161A and/or F164A substitutions, which were designed to disrupt the interactions with the RNA molecule, did not affect the ATPase activity but completely abolished the replication and transcription of viral RNA and the infectivity of CHIKV. Our study sheds light on the roles of the RNA helicase region in viral replication and provides insights that might be applicable to alphaviruses and other RNA viruses in general.",,"['Law, Yee-Song', 'Utt, Age', 'Tan, Yaw Bia', 'Zheng, Jie', 'Wang, Sainan', 'Chen, Ming Wei', 'Griffin, Patrick R.', 'Merits, Andres', 'Luo, Dahai']",,,,
,PMC,PPAR-γ in Macrophages Limits Pulmonary Inflammation and Promotes Host Recovery following Respiratory Viral Infection,http://dx.doi.org/10.1128/JVI.00030-19,PMC6475778,,,"Alveolar macrophages (AM) play pivotal roles in modulating host defense, pulmonary inflammation, and tissue injury following respiratory viral infections. However, the transcriptional regulation of AM function during respiratory viral infections is still largely undefined. Here we have screened the expression of 84 transcription factors in AM in response to influenza A virus (IAV) infection. We found that the transcription factor PPAR-γ was downregulated following IAV infection in AM through type I interferon (IFN)-dependent signaling. PPAR-γ expression in AM was critical for the suppression of exaggerated antiviral and inflammatory responses of AM following IAV and respiratory syncytial virus (RSV) infections. Myeloid PPAR-γ deficiency resulted in enhanced host morbidity and increased pulmonary inflammation following both IAV and RSV infections, suggesting that macrophage PPAR-γ is vital for restricting severe host disease development. Using approaches to selectively deplete recruiting monocytes, we demonstrate that PPAR-γ expression in resident AM is likely important in regulating host disease development. Furthermore, we show that PPAR-γ was critical for the expression of wound healing genes in AM. As such, myeloid PPAR-γ deficiency resulted in impaired inflammation resolution and defective tissue repair following IAV infection. Our data suggest a critical role of PPAR-γ expression in lung macrophages in the modulation of pulmonary inflammation, the development of acute host diseases, and the proper restoration of tissue homeostasis following respiratory viral infections. IMPORTANCE Respiratory viral infections, like IAV and respiratory syncytial virus (RSV) infections, impose great challenges to public health. Alveolar macrophages (AM) are lung-resident immune cells that play important roles in protecting the host against IAV and RSV infections. However, the underlying molecular mechanisms by which AM modulate host inflammation, disease development, and tissue recovery are not very well understood. Here we identify that PPAR-γ expression in AM is crucial to suppress pulmonary inflammation and diseases and to promote fast host recovery from IAV and RSV infections. Our data suggest that targeting macrophage PPAR-γ may be a promising therapeutic option in the future to suppress acute inflammation and simultaneously promote recovery from severe diseases associated with respiratory viral infections.",,"['Huang, Su', 'Zhu, Bibo', 'Cheon, In Su', 'Goplen, Nick P.', 'Jiang, Li', 'Zhang, Ruixuan', 'Peebles, R. Stokes', 'Mack, Matthias', 'Kaplan, Mark H.', 'Limper, Andrew H.', 'Sun, Jie']",,,,
,PMC,Simultaneous detection of 15 respiratory pathogens with a fluorescence probe melting curve analysis-based multiplex real-time PCR assay,,PMC6526376,,,"Acute respiratory tract infections are common worldwide and caused by a great diversity of pathogens. A rapid and accurate diagnosis method of respiratory infection is crucial for timely clinical intervention. Here, by combining fluorescence melting curve analysis and multiplex real-time assay, we developed a novel method which can simultaneously detect 15 respiratory viruses. The specificity for target genes was 100%, as assessed with a panel of 47 respiratory pathogens, which indicated no cross-reactions. The assay’s limits of detection at the nucleic acid level ranged from 5 copies/μL to 500 copies/μL nucleic acids. Compared with conventional culture method, our assay showed more than 75% sensitivity and 100% specificity for each respiratory pathogen in 384 clinical samples. Even more, the kappa correlation for all the pathogens ranged from 0.86 to 1.00. Overall, this method has the characteristics of high throughput, low cost and high sensitivity and precision, which demonstrated our method is well suited for routine clinical testing in respiratory infection.",,"['Liao, Shengyun', 'Wang, Lingli', 'Ji, Xiang', 'Chen, Jiandong', 'Li, Qiang', 'Ma, Lan']",,,,
,PMC,"World must prepare for inevitable flu pandemic, says WHO",http://dx.doi.org/10.1503/cmaj.109-5735,PMC6453672,,,,,"Vogel, Lauren",,,,
,PMC,"Mitochondrial Function, Metabolic Regulation, and Human Disease Viewed through the Prism of Sirtuin 4 (SIRT4) Functions",http://dx.doi.org/10.1021/acs.jproteome.9b00086,PMC6889813,,,"As cellular metabolic hubs, mitochondria are the main energy producers for the cell. These organelles host essential energy producing biochemical processes, including the TCA cycle, fatty acid oxidation, and oxidative phosphorylation. An accumulating body of literature has demonstrated that a majority of mitochondrial proteins are decorated with diverse posttranslational modifications (PTMs). Given the critical roles of these proteins in cellular metabolic pathways and response to environmental stress or pathogens, understanding the role of PTMs in regulating their functions has become an area of intense investigation. A major family of enzymes that regulate PTMs within the mitochondria are sirtuins (SIRTs). Albeit until recently the least understood sirtuin, SIRT4 has emerged as an enzyme capable of removing diverse PTMs from its substrates, thereby modulating their functions. SIRT4 was shown to have ADP-ribosyltransferase, deacetylase, lipoamidase, and deacylase enzymatic activities. As metabolic dysfunction is linked to human disease, SIRT4 levels and activities have been implicated in modulating susceptibility to hyperinsulinemia and diabetes, liver disease, cancer, neurodegeneration, heart disease, aging, and pathogenic infections. Therefore, SIRT4 has emerged as a possible candidate for targeted therapeutics. Here, we discuss the diverse enzymatic activities and substrates of SIRT4 and its roles in human health and disease.",,"['Betsinger, Cora N.', 'Cristea, Ileana M.']",,,,
,PMC,Climate change and infectious diseases: What can we expect?,http://dx.doi.org/10.14745/ccdr.v45i04a01,PMC6587697,,,"Global climate change, driven by anthropogenic greenhouse gas emissions, is being particularly felt in Canada, with warming generally greater than in the rest of the world. Continued warming will be accompanied by changes in precipitation, which will vary across the country and seasons, and by increasing climate variability and extreme weather events. Climate change will likely drive the emergence of infectious diseases in Canada by northward spread from the United States and introduction from elsewhere in the world via air and sea transport. Diseases endemic to Canada are also likely to re-emerge. This special issue describes key infectious disease risks associated with climate change. These include emergence of tick-borne diseases in addition to Lyme disease, the possible introduction of exotic mosquito-borne diseases such as malaria and dengue, more epidemics of Canada-endemic vector-borne diseases such as West Nile virus, and increased incidence of foodborne illnesses. Risk is likely to be compounded by an aging population affected by chronic diseases, which results in greater sensitivity to infectious diseases. Identifying emerging disease risks is essential to assess our vulnerability, and a starting point to identify where public health effort is required to reduce the vulnerability and exposure of the Canadian population.",,"['Ogden, NH', 'Gachon, P']",,,,
,PMC,Arbidol and Other Low-Molecular-Weight Drugs That Inhibit Lassa and Ebola Viruses,http://dx.doi.org/10.1128/JVI.02185-18,PMC6450122,,,"Antiviral therapies that impede virus entry are attractive because they act on the first phase of the infectious cycle. Drugs that target pathways common to multiple viruses are particularly desirable when laboratory-based viral identification may be challenging, e.g., in an outbreak setting. We are interested in identifying drugs that block both Ebola virus (EBOV) and Lassa virus (LASV), two unrelated but highly pathogenic hemorrhagic fever viruses that have caused outbreaks in similar regions in Africa and share features of virus entry: use of cell surface attachment factors, macropinocytosis, endosomal receptors, and low pH to trigger fusion in late endosomes. Toward this goal, we directly compared the potency of eight drugs known to block EBOV entry with their potency as inhibitors of LASV entry. Five drugs (amodiaquine, apilimod, arbidol, niclosamide, and zoniporide) showed roughly equivalent degrees of inhibition of LASV and EBOV glycoprotein (GP)-bearing pseudoviruses; three (clomiphene, sertraline, and toremifene) were more potent against EBOV. We then focused on arbidol, which is licensed abroad as an anti-influenza drug and exhibits activity against a diverse array of clinically relevant viruses. We found that arbidol inhibits infection by authentic LASV, inhibits LASV GP-mediated cell-cell fusion and virus-cell fusion, and, reminiscent of its activity on influenza virus hemagglutinin, stabilizes LASV GP to low-pH exposure. Our findings suggest that arbidol inhibits LASV fusion, which may partly involve blocking conformational changes in LASV GP. We discuss our findings in terms of the potential to develop a drug cocktail that could inhibit both LASV and EBOV. IMPORTANCE Lassa and Ebola viruses continue to cause severe outbreaks in humans, yet there are only limited therapeutic options to treat the deadly hemorrhagic fever diseases they cause. Because of overlapping geographic occurrences and similarities in mode of entry into cells, we seek a practical drug or drug cocktail that could be used to treat infections by both viruses. Toward this goal, we directly compared eight drugs, approved or in clinical testing, for the ability to block entry mediated by the glycoproteins of both viruses. We identified five drugs with approximately equal potencies against both. Among these, we investigated the modes of action of arbidol, a drug licensed abroad to treat influenza infections. We found, as shown for influenza virus, that arbidol blocks fusion mediated by the Lassa virus glycoprotein. Our findings encourage the development of a combination of approved drugs to treat both Lassa and Ebola virus diseases.",,"['Hulseberg, C. E.', 'Fénéant, L.', 'Szymańska-de Wijs, K. M.', 'Kessler, N. P.', 'Nelson, E. A.', 'Shoemaker, C. J.', 'Schmaljohn, C. S.', 'Polyak, S. J.', 'White, J. M.']",,,,
,PMC,Coronavirus Endoribonuclease Activity in Porcine Epidemic Diarrhea Virus Suppresses Type I and Type III Interferon Responses,http://dx.doi.org/10.1128/JVI.02000-18,PMC6450110,,,"Identifying viral antagonists of innate immunity and determining if they contribute to pathogenesis are critical for developing effective strategies to control emerging viruses. Previously, we reported that an endoribonuclease (EndoU) encoded by murine coronavirus plays a pivotal role in evasion of host innate immune defenses in macrophages. Here, we asked if the EndoU activity of porcine epidemic diarrhea coronavirus (PEDV), which causes acute diarrhea in swine, plays a role in antagonizing the innate response in porcine epithelial cells and macrophages, the sites of viral replication. We constructed an infectious clone of PEDV-Colorado strain (icPEDV-wt) and an EndoU-mutant PEDV (icPEDV-EnUmt) by changing the codon for a catalytic histidine residue of EndoU to alanine (His226Ala). We found that both icPEDV-wt and icPEDV-EnUmt propagated efficiently in interferon (IFN)-deficient Vero cells. In contrast, the propagation of icPEDV-EnUmt was impaired in porcine epithelial cells (LLC-PK1), where we detected an early and robust transcriptional activation of type I and type III IFNs. Infection of piglets with the parental Colorado strain, icPEDV-wt, or icPEDV-EnUmt revealed that all viruses replicated in the gut and induced diarrhea; however, there was reduced viral shedding and mortality in the icPEDV-EnUmt-infected animals. These results demonstrate that EndoU activity is not required for PEDV replication in immortalized, IFN-deficient Vero cells, but is important for suppressing the IFN response in epithelial cells and macrophages, which facilitates replication, shedding, and pathogenesis in vivo. We conclude that PEDV EndoU activity is a key virulence factor that suppresses both type I and type III IFN responses. IMPORTANCE Coronaviruses (CoVs) can emerge from an animal reservoir into a naive host species to cause pandemic respiratory or gastrointestinal diseases with significant mortality in humans or domestic animals. Porcine epidemic diarrhea virus (PEDV), an alphacoronavirus (alpha-CoV), infects gut epithelial cells and macrophages, inducing diarrhea and resulting in high mortality in piglets. How PEDV suppresses the innate immune response was unknown. We found that mutating a viral endoribonuclease, EndoU, results in a virus that activates both the type I interferon response and the type III interferon response in macrophages and epithelial cells. This activation of interferon resulted in limited viral replication in epithelial cell cultures and was associated with reduced virus shedding and mortality in piglets. This study reveals a role for EndoU activity as a virulence factor in PEDV infection and provides an approach for generating live-attenuated vaccine candidates for emerging coronaviruses.",,"['Deng, Xufang', 'van Geelen, Albert', 'Buckley, Alexandra C.', 'O’Brien, Amornrat', 'Pillatzki, Angela', 'Lager, Kelly M.', 'Faaberg, Kay S.', 'Baker, Susan C.']",,,,
,PMC,Molecular characterization of a Korean porcine epidemic diarrhea virus strain NB1,,PMC6450166,,,"In Korea, for the past 30 years (1987–present), porcine epidemic diarrhea (PED) has been established as an endemic situation in which multiple genogroups of classical G1 and G2b, and the recently introduced pandemic G2a, coexisted. Because of the dynamic nature of the virus, continuous field monitoring for PEDV strains is required. This study is the first to reveal prevalence of PEDV in 9 sampling provinces, with an overall detection rate of 6.70%. Porcine endemic diarrhea virus (PEDV) was present in pigs of all ages, especially in the non-PED vaccinated groups. The highest detection rate was in the finisher group (2.34%), followed by that in the newborn group (1.56%). Secondly, using Sanger sequencing, this study recovered a complete genome (28 005 nucleotides long) of NB1 strain from a farm severely affected by PED. Analyses of nucleotide and deduced amino acid sequences showed that NB1 differed from 18 other Korean PEDV mostly in 4 protein coding genes: ORF1a, ORF1b, S, and N. Two amino acid substitutions (V635E and Y681Q) in the COE and S1D neutralizing epitopes of NB1 resulted in antigenic index alteration of the adjacent sites, one of which contributed to a mutation that escaped neutralizing antibodies.",,"['Chung, Hee-Chun', 'Nguyen, Van Giap', 'Le Huynh, Thi My', 'Moon, Hyoung-Joon', 'Kang, Bo-Kyu', 'Kim, Sung-Jae', 'Kim, Hye-Kwon', 'Park, Seong-Jun', 'Park, Kun-Taek', 'Park, Yong-Ho', 'Park, Bong-Kyun']",,,,
,PMC,Vaccine usage in western Canadian cow-calf herds,,PMC6417607,,,"The aims of this study were to describe when and how vaccines are administered during the production cycle in cow-calf herds in western Canada, as well as the factors that influence vaccine usage as reported by producers. The most commonly used vaccines were bovine viral diarrhea virus/infectious bovine rhinotracheitis (BVDV/IBR) in adult animals and clostridial vaccines in calves. While there has been improvement in usage of reproductive and respiratory viral vaccines since previous studies, there are still several areas in which uptake could be improved. Only 72% of herd owners vaccinated their bulls for at least 1 disease. Not all producers are vaccinating their calves for clostridial diseases, and 15% of producers did not vaccinate their calves for respiratory disease before weaning. One goal of increasing vaccine use is to obtain better infection prevention and control and decrease antimicrobial use in cow-calf herds. Two areas in which antimicrobials are commonly used, but vaccine uptake is limited, are foot rot in adult cows and diarrhea in calves.",,"['Waldner, Cheryl L.', 'Parker, Sarah', 'Campbell, John R.']",,,,
,PMC,What makes non-cirrhotic portal hypertension a common disease in India? Analysis for environmental factors,http://dx.doi.org/10.4103/ijmr.IJMR_1405_17,PMC6676844,31411170,CC BY-NC-SA,"In India, an unexplained enteropathy is present in a majority of non-cirrhotic intrahepatic portal hypertension (NCIPH) patients. Small intestinal bacterial contamination and tropical enteropathy could trigger inflammatory stimuli and activate the endothelium in the portal venous system. Groundwater contaminated with arsenic is an environmental factor of epidemic proportions in large areas of India which has similar consequences. Von Willebrand factor (a sticky protein) expressed by activated endothelium may promote formation of platelet microthrombi and occlusion of intrahepatic portal vein branches leading to NCIPH. Environmental factors linked to suboptimal hygiene and sanitation, which enter through the gastrointestinal (GI) tract, predispose to platelet plugging onto activated endothelium in portal microcirculation. Thus, NCIPH, an example of poverty linked thrombophilia, is a disease mainly affecting the lower socio-economic strata of Indian population. Public health measures to improve sanitation, provide clean drinking water and eliminate arsenic contamination of drinking water are urgently needed. Till such time as these environmental factors are addressed, NCIPH is likely to remain 'an Indian disease'.",2019 Apr,"['Goel, Ashish', 'Ramakrishna, Banumathi', 'Zachariah, Uday', 'Sajith, K.G.', 'Burad, Deepak K.', 'Kodiatte, Thomas A.', 'Keshava, Shyamkumar N.', 'Balasubramanian, K.A.', 'Elias, Elwyn', 'Eapen, C.E.']",Indian J Med Res,,,
,PMC,Emerging/re-emerging viral diseases & new viruses on the Indian horizon,http://dx.doi.org/10.4103/ijmr.IJMR_1239_18,PMC6676836,31411169,CC BY-NC-SA,"Infectious diseases remain as the major causes of human and animal morbidity and mortality leading to significant healthcare expenditure in India. The country has experienced the outbreaks and epidemics of many infectious diseases. However, enormous successes have been obtained against the control of major epidemic diseases, such as malaria, plague, leprosy and cholera, in the past. The country's vast terrains of extreme geo-climatic differences and uneven population distribution present unique patterns of distribution of viral diseases. Dynamic interplays of biological, socio-cultural and ecological factors, together with novel aspects of human-animal interphase, pose additional challenges with respect to the emergence of infectious diseases. The important challenges faced in the control and prevention of emerging and re-emerging infectious diseases range from understanding the impact of factors that are necessary for the emergence, to development of strengthened surveillance systems that can mitigate human suffering and death. In this article, the major emerging and re-emerging viral infections of public health importance have been reviewed that have already been included in the Integrated Disease Surveillance Programme.",2019 Apr,"['Mourya, Devendra T.', 'Yadav, Pragya D.', 'Ullas, P.T.', 'Bhardwaj, Sumit D.', 'Sahay, Rima R.', 'Chadha, Mandeep S.', 'Shete, Anita M.', 'Jadhav, Santosh', 'Gupta, Nivedita', 'Gangakhedkar, Raman R.', 'Khasnobis, Pradeep', 'Singh, Sujeet K.']",Indian J Med Res,,,
,PMC,Translational recoding signals: Expanding the synthetic biology toolbox,http://dx.doi.org/10.1074/jbc.REV119.006348,PMC6514632,,,"Innovation follows discovery. If the 20th century was a golden age of discovery in the biomolecular biosciences, the current century may be remembered by the explosion of beneficial devices and therapies conceived by the bioengineers of the era. Much as the development of solid-state electronic components made possible the information revolution, the rational combining of millions of basic molecular control modules will enable the development of highly sophisticated biomachines that will make today's smartphones appear rudimentary. The molecular toolbox is already well-stocked, particularly in our ability to manipulate DNA, control transcription, generate functionally novel hybrid proteins, and expand the genetic code to include unnatural amino acids. This review focuses on how RNA-based regulatory modules that direct alternative readings of the genetic code can be employed as basic circuit components to expand our ability to control gene expression.",,"Dinman, Jonathan D.",,,,
,PMC,Empiric Antibiotic Therapy in the Treatment of Community-acquired Pneumonia in a General Hospital in Saudi Arabia,http://dx.doi.org/10.4103/jgid.jgid_84_18,PMC6555230,31198310,CC BY-NC-SA,"BACKGROUND: Guideline-based empiric antimicrobial therapy is recommended for the treatment of community-acquired pneumonia (CAP). In this study, we evaluate the pattern of empiric antibiotics of CAP patients. MATERIALS AND METHODS: Patients with CAP were retrieved from the health information unit using the International Classification of Diseases, Ninth Revision. The electronic pharmacy database was used to retrieve prescribed antibiotics and the duration of therapy for each antibiotic. RESULTS: A total of 1672 adult patients were included in the study and 868 (52%) were male. Of all the patients, 47 (2.8%) were admitted to the intensive care unit (ICU). The most frequently used antibiotics were levofloxacin (68.12%), ceftriaxone (37.7%), imipenem-cilastatin (32.5%), and azithromycin (20.6%). The mean days of therapy of each of these antibiotics were 3.2, 2.8, 4.4, and 2.9, respectively. A combination therapy of levofloxacin and imipenem-cilastatin was prescribed for 355 (21.8%) of non-ICU patients versus 20 (60.6%) of ICU patients (P = 0.0007). Imipenem-cilastatin was prescribed for 518 (31.8%) of non-ICU patients versus 25 (56.8%) of ICU patients (P = 0.0009). Levofloxacin was prescribed for 1106 (68%) of non-ICU patients versus 33 (75%) of ICU patients (P = 0.412). Ceftriaxone use decreased significantly from 40.9% in 2013 to 25.9% in 2016 (P = 0.034). In addition, levofloxacin use increased from 63.7% to 75% (P = 0.63). CONCLUSION: The most commonly used antibiotics were levofloxacin, ceftriaxone, imipenem-cilastatin, and azithromycin. The data call for further refinement and prospective audit of antibiotic use in CAP, especially in non-ICU settings.",2019 Apr-Jun,"['Al-Tawfiq, Jaffar A.', 'Momattin, Hisham', 'Hinedi, Kareem']",J Glob Infect Dis,,,
,PMC,"Relationship Between Antimicrobial Prescribing and Antimicrobial Resistance Among UTI Patients at Buraidah Central Hospital, Saudi Arabia",http://dx.doi.org/10.4103/jpbs.JPBS_217_18,PMC6537636,31148893,CC BY-NC-SA,"INTRODUCTION: Most of the decisions regarding diagnosis and treatment are based on laboratory test results. Urinary tract infections (UTIs) are among the most common infections in humans. The changing antimicrobial sensitivity in UTI requires appropriate antibiotics. Antimicrobial resistance is an emerging problem in the Kingdom of Saudi Arabia where the complete reversal of antimicrobial resistance is difficult due to irrational use of antibiotics. OBJECTIVES: This study aimed to determine the most common bacterial agents causing UTI in different seasons among patients who were admitted to Buraidah Central Hospital (BCH), Saudi Arabia. The study also evaluated the link between prescribing and resistance toward antimicrobials. MATERIALS AND METHODS: A 6-month retrospective study was conducted among adult patients who were admitted to the inpatient department at BCH. A total of 379 files were collected from microbiological laboratory for inpatients. RESULTS: Most UTI-causing bacteria prevailed in the same season. Of 15 bacterial strains, 12 were significantly correlated with 20 (of a total of 40) antibiotics that were used. Most bacteria were gram-negative. Gram-negative bacilli including Escherichia coli, Klebsiella spp., and Pseudomonadaceae and gram-positive Enterococcus faecalis were most frequently causing UTIs. CONCLUSION: Overall prevalence of antibiotic resistance was negative in bacterial isolates. However, the relationship between antimicrobial prescribing and antimicrobial resistance was significantly negative among UTI patients in BCH, Saudi Arabia.",2019 Apr-Jun,"['Alsohaim, Sulaiman I. A.', 'Bawadikji, Abdulkader A.', 'Elkalmi, Ramadan', 'Mahmud, Mohammed Imad Al-deen M.', 'Hassali, Mohamed Azmi']",J Pharm Bioallied Sci,,,
,PMC,Occupational adverse effects and protective factors in bronchoscopy,http://dx.doi.org/10.21037/jtd.2019.03.73,PMC6531707,,,"The application of bronchoscopy has resolved a series of diagnostic and treatment challenges in pulmonary diseases. However, the occupational adverse effects experienced by healthcare workers in interventional pulmonology should receive increasing attention. Various aspects of adverse effects in bronchoscopy are often neglected, and healthcare workers frequently ignore guidelines for personal protection against factors such as radiation, smoke, pathogenic microbiological aerosols, cryogenic gas, etc. Thus, there is an urgent need to conduct additional research to establish standards for occupational adverse effects and protective measures related to bronchoscopy.",,"['Chen, Kai', 'Bai, Chong']",,,,
,PMC,Wet Markets and Food Safety: TripAdvisor for Improved Global Digital Surveillance,http://dx.doi.org/10.2196/11477,PMC6462893,30932867,CC BY,"BACKGROUND: Wet markets are markets selling fresh meat and produce. Wet markets are critical for food security and sustainable development in their respective regions. Due to their cultural significance, they attract numerous visitors and consequently generate tourist-geared information on the Web (ie, on social networks such as TripAdvisor). These data can be used to create a novel, international wet market inventory to support epidemiological surveillance and control in such settings, which are often associated with negative health outcomes. OBJECTIVE: Using social network data, we aimed to assess the level of wet markets’ touristic importance on the Web, produce the first distribution map of wet markets of touristic interest, and identify common diseases facing visitors in these settings. METHODS: A Google search was performed on 31 food market–related keywords, with the first 150 results for each keyword evaluated based on their relevance to tourism. Of all these queries, wet market had the highest number of tourism-related Google Search results; among these, TripAdvisor was the most frequently-occurring travel information aggregator, prompting its selection as the data source for this study. A Web scraping tool (ParseHub) was used to extract wet market names, locations, and reviews from TripAdvisor. The latter were searched for disease-related content, which enabled assignment of GeoSentinel diagnosis codes to each. This syndromic categorization was overlaid onto a mapping of wet market locations. Regional prevalence of the most commonly occurring symptom group - food poisoning - was then determined (ie, by dividing the number of wet markets per continent with more than or equal to 1 review containing this syndrome by the total number of wet markets on that continent with syndromic information). RESULTS: Of the 1090 hits on TripAdvisor for wet market, 36.06% (393/1090) conformed to the query’s definition; wet markets were heterogeneously distributed: Asia concentrated 62.6% (246/393) of them, Europe 19.3% (76/393), North America 7.9% (31/393), Oceania 5.1% (20/393), Africa 3.1% (12/393), and South America 2.0% (8/393). Syndromic information was available for 14.5% (57/393) of wet markets. The most frequently occurring syndrome among visitors to these wet markets was food poisoning, accounting for 54% (51/95) of diagnoses. Cases of this syndrome were identified in 56% (22/39) of wet markets with syndromic information in Asia, 71% (5/7) in Europe, and 71% (5/7) in North America. All wet markets in South America and Oceania reported food poisoning cases, but the number of reviews with syndromic information was very limited in these regions (n=2). CONCLUSIONS: The map produced illustrates the potential role of touristically relevant social network data to support global epidemiological surveillance. This includes the possibility to approximate the global distribution of wet markets and to identify diseases (ie, food poisoning) that are most prevalent in such settings.",2019 Apr 1,"['Kogan, Nicole E', 'Bolon, Isabelle', 'Ray, Nicolas', 'Alcoba, Gabriel', 'Fernandez-Marquez, Jose L', 'Müller, Martin M', 'Mohanty, Sharada P', 'Ruiz de Castañeda, Rafael']",JMIR Public Health Surveill,,,
,PMC,Decoding type I and III interferon signalling during viral infection,http://dx.doi.org/10.1038/s41564-019-0421-x,PMC6554024,,,"Interferon (IFN)-mediated antiviral responses are central to host defence against viral infection. Despite the existence of at least 20 IFNs, there are only three known cell surface receptors. IFN signalling and viral evasion mechanisms form an immensely complex network that differs across species. In this Review, we begin by highlighting some of the advances that have been made towards understanding the complexity of differential IFN signalling inputs and outputs that contribute to antiviral defences. Next, we explore some of the ways viruses can interfere with, or circumvent, these defences. Lastly, we address the largely under-reviewed impact of IFN signalling on host tropism, and we offer perspectives on the future of research into IFN signalling complexity and viral evasion across species.",,"['Mesev, Emily V.', 'LeDesma, Robert A.', 'Ploss, Alexander']",,,,
,PMC,Association between IFN-γ +874 T/A (Rs2430561) Polymorphisms and Bipolar 1 Disorder: A Study in an Ethnic Iranian Population,,PMC6590944,,,"BACKGROUND: The pathophysiology of bipolar 1 disorder (B1D), a major psychiatric disorder with inflammatory origins and structural changes in the brain, is of great interest to researchers. Pro-inflammatory biomarkers and specific gene expression play pivotal roles in B1D development, and IFN-γ has emerged as an important inflammatory marker. The aim of this research was to determine whether the INF-γ +874 T/A polymorphism is associated with B1D susceptibility in an ethnic Iranian population. METHODS: The IFN-γ +874 T/A (rs2430561) gene polymorphism was studied in 106 B1D patients and 109 control subjects using sequence specific primers (SSPs) and amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). RESULTS: Significant statistical differences in IFN-γ +874 T/A polymorphism genotype distribution were found between the patients and control subjects (P = 0.0006). Decreased risk of B1D was detected in the codominant model (T/T vs T/A and A/A, OR = 0.19, 95% CI = 0.07-0.49 for T/A, OR = 0.38, 95% CI = 0.12-1.24 for A/A, P value=0.0006), and in the dominant model (T/T vs T/A-A/A, OR = 0.21, 95% CI = 0.08-0.54, P = 0.0005). However, no significant difference in the IFN-γ polymorphism allele distribution was found between the two groups (P = 0.25). CONCLUSION: The IFN-γ +874 T/A polymorphism may have a significant role in BID development.",,"['Fatemi Nayeri, Mahdieh', 'Talaei, Ali', 'Tavakkol Afshari, Jalil', 'Nikpoor, Amin Reza', 'Talaei, Andisheh', 'Ganjali, Rashin']",,,,
,PMC,Optimizing Post-Intensive Care Unit Rehabilitation,http://dx.doi.org/10.5152/TurkThoracJ.2018.18172,PMC6453631,,,"Survivors of intensive care unit (ICU) admission face unique challenges after hospital discharge. In addition to an increased overall mortality and rates of hospital readmission, patients often experience difficulties in physical functioning, cognition, and mental health, which are collectively termed post-intensive care syndrome. To this date, there are no established strategies to address these deleterious outcomes. A number of studies have examined various unique methods to prevent and treat PICS symptoms, including early physical and occupational therapy, providing post-discharge education, or facilitating routine follow up in post-ICU clinics. These trials have yet to demonstrate any substantial or meaningful effect in post-ICU patients and collectively reinforce the need for further research to identify effective intervention for patients who survive critical illness.",,"['Held, Natalie', 'Moss, Marc']",,,,
,PMC,Guideline on writing a case report,http://dx.doi.org/10.4103/UA.UA_177_18,PMC6476221,31040594,CC BY-NC-SA,"Research is an important competency that should be mastered by medical professionals. It provides an opportunity for physicians to develop numerous skills including communication, collaboration, time management, and teamwork. Case report, as a research design, describes important scientific observations that are encountered in a clinical setting to expand our knowledge base. Preparing a case report is far easier than conducting any other elaborative research design. Case report, with its main components, should be focused and delivers a clear message. In this article, the key components of a case report were described with the aim of providing guidance to novice authors to improve the quality of their reporting.",2019 Apr-Jun,"['Alsaywid, Basim Saleh', 'Abdulhaq, Nada Mansour']",Urol Ann,,,
,PMC,Impact of Rapid Molecular Diagnostic Testing of Respiratory Viruses on Outcomes of Adults Hospitalized with Respiratory Illness: a Multicenter Quasi-experimental Study,http://dx.doi.org/10.1128/JCM.01727-18,PMC6440765,,,"A standard multiplex PCR offers comprehensive testing for respiratory viruses. However, it has traditionally been performed in a referral laboratory with a lengthy turnaround time, which can reduce patient flow through the hospital. We aimed to determine whether the introduction of a rapid PCR, but with limited targets (Cepheid Xpert Flu/RSV XC), was associated with improved outcomes for adults hospitalized with respiratory illness. A controlled quasi-experimental study was conducted across three hospitals in New South Wales, Australia. Intervention groups received standard multiplex PCR during the preimplementation, July to December 2016 (n = 953), and rapid PCR during the postimplementation, July to December 2017 (n = 1,209). Control groups (preimplementation, n = 937, and postimplementation, n = 1,102) were randomly selected from adults hospitalized with respiratory illness during the same periods. The outcomes were hospital length of stay (LOS) and microbiology test utilization (blood culture, urine culture, sputum culture, and respiratory bacterial and virus serologies). The introduction of rapid PCR was associated with a nonsignificant 8.9-h reduction in median LOS (95% confidence interval [CI], −21.5 h to 3.7 h; P = 0.17) for all patients and a significant 21.5-h reduction in median LOS (95% CI, −36.8 h to −6.2 h; P < 0.01) among patients with positive test results in an adjusted difference-in-differences analysis. For patients receiving test results before disposition, rapid PCR use was associated with a significant reduction in LOS, irrespective of test results. Compared with standard PCR testing, rapid PCR use was significantly associated with fewer blood culture (adjusted odds ratio [aOR], 0.67; 95% CI, 0.5 to 0.82; P < 0.001), sputum culture (aOR, 0.56; 95% CI, 0.47 to 0.68, P < 0.001), bacterial serology (aOR, 0.44; 95% CI, 0.35 to 0.55, P < 0.001) and viral serology (aOR, 0.42; 95% CI, 0.33 to 0.53, P < 0.001) tests, but not with fewer urine culture tests (aOR, 0.94; 95% CI, 0.78 to 1.12, P = 0.48). Rapid PCR testing of adults hospitalized with respiratory illnesses can deliver benefits to patients and reduce resource utilization. Future research should consider a formal economic analysis and assess its potential impacts on clinical decision making.",,"['Wabe, Nasir', 'Li, Ling', 'Lindeman, Robert', 'Yimsung, Ruth', 'Dahm, Maria R.', 'McLennan, Susan', 'Clezy, Kate', 'Westbrook, Johanna I.', 'Georgiou, Andrew']",,,,
,PMC,Simultaneous Detection and Differentiation between Wild-Type and Vaccine Measles Viruses by a Multiplex Real-Time Reverse Transcription-PCR Assay,http://dx.doi.org/10.1128/JCM.01828-18,PMC6440764,,,"Measles is one of the most contagious viral respiratory infections and was declared to be eliminated from Canada in 1998; however, measles cases and outbreaks still occur every year through reintroduction from other parts of the world. Laboratory confirmation of measles virus (MV) RNA by real-time PCR provides a definitive diagnosis, and molecular analysis to determine the genotype is the only way to distinguish between wild-type and vaccine strains. This distinction is important since live attenuated vaccine strains are able to replicate in the patient and can be associated with rash and fever but are poorly transmissible, if at all. Prompt reporting of measles cases to local authorities, including differentiation between wild-type and vaccine strains, allows for optimal management and contact tracing. The development and validation of a multiplex real-time reverse transcription-PCR (rtRT-PCR) assay for the simultaneous detection and differentiation of the Moraten and Schwarz vaccine strains from presumptive wild-type MV in a format that can be easily implemented for high-throughput testing of patient samples are reported here. This assay is sensitive, specific, reproducible, and 100% accurate in comparison with the gold standard comparator assay.",,"['Pabbaraju, Kanti', 'Gill, Kara', 'Wong, Anita A.', 'Tipples, Graham A.', 'Hiebert, Joanne', 'Severini, Alberto', 'Fonseca, Kevin', 'Tellier, Raymond']",,,,
,PMC,"Pathogenesis, Host Innate Immune Response, and Aerosol Transmission of Influenza D Virus in Cattle",http://dx.doi.org/10.1128/JVI.01853-18,PMC6430558,,,"The recently discovered influenza D virus (IDV) of the Orthomyxoviridae family has been detected in swine and ruminants with a worldwide distribution. Cattle are considered to be the primary host and reservoir, and previous studies suggested a tropism of IDV for the upper respiratory tract and a putative role in the bovine respiratory disease complex. This study aimed to characterize the pathogenicity of IDV in naive calves as well as the ability of this virus to transmit by air. Eight naive calves were infected by aerosol with a recent French isolate, D/bovine/France/5920/2014. Results show that IDV replicates not only in the upper respiratory tract but also in the lower respiratory tract (LRT), inducing moderate bronchopneumonia with restricted lesions of interstitial pneumonia. Inoculation was followed by IDV-specific IgG1 production as early as 10 days postchallenge and likely both Th1 and Th2 responses. Study of the innate immune response in the LRT of IDV-infected calves indicated the overexpression of pathogen recognition receptors and of chemokines CCL2, CCL3, and CCL4, but without overexpression of genes involved in the type I interferon pathway. Finally, virological examination of three aerosol-sentinel animals, housed 3 m apart from inoculated calves (and thus subject to infection by aerosol transmission), and IDV detection in air samples collected in different areas showed that IDV can be airborne transmitted and infect naive contact calves on short distances. This study suggests that IDV is a respiratory virus with moderate pathogenicity and probably a high level of transmission. It consequently can be considered predisposing to or a cofactor of respiratory disease. IMPORTANCE Influenza D virus (IDV), a new genus of the Orthomyxoviridae family, has a broad geographical distribution and can infect several animal species. Cattle are so far considered the primary host for IDV, but the pathogenicity and the prevalence of this virus are still unclear. We demonstrated that under experimental conditions (in a controlled environment and in the absence of coinfecting pathogens), IDV is able to cause mild to moderate disease and targets both the upper and lower respiratory tracts. The virus can transmit by direct as well as aerosol contacts. While this study evidenced overexpression of pathogen recognition receptors and chemokines in the lower respiratory tract, IDV-specific IgG1 production as early as 10 days postchallenge, and likely both Th1 and Th2 responses, further studies are warranted to better understand the immune responses triggered by IDV and its role as part of the bovine respiratory disease complex.",,"['Salem, Elias', 'Hägglund, Sara', 'Cassard, Hervé', 'Corre, Tifenn', 'Näslund, Katarina', 'Foret, Charlotte', 'Gauthier, David', 'Pinard, Anne', 'Delverdier, Maxence', 'Zohari, Siamak', 'Valarcher, Jean-François', 'Ducatez, Mariette', 'Meyer, Gilles']",,,,
,PMC,Transmission of a Novel Genotype of Hepatitis E Virus from Bactrian Camels to Cynomolgus Macaques,http://dx.doi.org/10.1128/JVI.02014-18,PMC6430554,,,"Hepatitis E virus (HEV) is zoonotic and a major cause of acute viral hepatitis worldwide. Recently, we identified a novel HEV genotype 8 (HEV8) in Bactrian camels in Xinjiang, China. However, the epidemiology, pathogenicity, and zoonotic potential of HEV8 are unclear. Here, we present the prevalence of HEV8 in China and investigate its pathogenicity and cross-species transmission in cynomolgus macaques. Fresh fecal and milk samples from Bactrian camels collected from four provinces/regions in China were screened for HEV RNA by reverse transcriptase PCR (RT-PCR). An HEV8-positive sample was used to inoculate two cynomolgus macaques to examine the potential for cross-species infection. The pathogenicity of HEV8 was analyzed by testing HEV markers and liver function during the study period and histopathology of liver biopsy specimens at 3, 13, and 25 weeks postinoculation. Extrahepatic replication was tested by using reverse transcriptase quantitative PCR (RT-qPCR) and immunofluorescence assays. The overall prevalence of HEV8 RNA in Chinese Bactrian camels was 1.4% (4/295), and positive samples were found in three different provinces/regions in China. Histopathology confirmed acute and chronic HEV8 infections in the two monkeys. Multiple tissues were positive for HEV RNA and ORF2 proteins. Renal pathology was observed in the monkey with chronic hepatitis. Whole-genome sequencing showed only 1 to 3 mutations in the HEV8 in the fecal samples from the two monkeys compared to that from the camel. HEV8 is circulating in multiple regions in China. Infection of two monkeys with HEV8 induced chronic and systemic infections, demonstrating the high potential zoonotic risk of HEV8. IMPORTANCE It is estimated that one-third of the world population have been exposed to hepatitis E virus (HEV). In developed countries and China, zoonotic HEV strains are responsible for almost all acute and chronic HEV infection cases. It is always of immediate interest to investigate the zoonotic potential of novel HEV strains. In 2016, we discovered a novel HEV genotype, HEV8, in Bactrian camels, but the epidemiology, zoonotic potential, and pathogenicity of the virus were unknown. In the present study, we demonstrated that HEV8 was circulating in multiple regions in China and was capable of infecting cynomolgus macaques, a surrogate for humans, posing high risk of zoonosis. Chronic hepatitis, systemic infection, and renal pathology were observed. Collectively, these data indicate that HEV8 exhibits a high potential for zoonotic transmission. Considering the importance of Bactrian camels as livestock animals, risk groups, such as camelid meat and milk consumers, should be screened for HEV8 infection.",,"['Wang, Lin', 'Teng, Jade L. L.', 'Lau, Susanna K. P.', 'Sridhar, Siddharth', 'Fu, Hongwei', 'Gong, Wanyun', 'Li, Manyu', 'Xu, Qieshi', 'He, Yunye', 'Zhuang, Hui', 'Woo, Patrick C. Y.', 'Wang, Ling']",,,,
,PMC,Cryo-electron Microscopy Structures of Novel Viruses from Mud Crab Scylla paramamosain with Multiple Infections,http://dx.doi.org/10.1128/JVI.02255-18,PMC6430526,,,"Viruses associated with sleeping disease (SD) in crabs cause great economic losses to aquaculture, and no effective measures are available for their prevention. In this study, to help develop novel antiviral strategies, single-particle cryo-electron microscopy was applied to investigate viruses associated with SD. The results not only revealed the structure of mud crab dicistrovirus (MCDV) but also identified a novel mud crab tombus-like virus (MCTV) not previously detected using molecular biology methods. The structure of MCDV at a 3.5-Å resolution reveals three major capsid proteins (VP1 to VP3) organized into a pseudo-T=3 icosahedral capsid, and affirms the existence of VP4. Unusually, MCDV VP3 contains a long C-terminal region and forms a novel protrusion that has not been observed in other dicistrovirus. Our results also reveal that MCDV can release its genome via conformation changes of the protrusions when viral mixtures are heated. The structure of MCTV at a 3.3-Å resolution reveals a T= 3 icosahedral capsid with common features of both tombusviruses and nodaviruses. Furthermore, MCTV has a novel hydrophobic tunnel beneath the 5-fold vertex and 30 dimeric protrusions composed of the P-domains of the capsid protein at the 2-fold axes that are exposed on the virion surface. The structural features of MCTV are consistent with a novel type of virus. IMPORTANCE Pathogen identification is vital for unknown infectious outbreaks, especially for dual or multiple infections. Sleeping disease (SD) in crabs causes great economic losses to aquaculture worldwide. Here we report the discovery and identification of a novel virus in mud crabs with multiple infections that was not previously detected by molecular, immune, or traditional electron microscopy (EM) methods. High-resolution structures of pathogenic viruses are essential for a molecular understanding and developing new disease prevention methods. The three-dimensional (3D) structure of the mud crab tombus-like virus (MCTV) and mud crab dicistrovirus (MCDV) determined in this study could assist the development of antiviral inhibitors. The identification of a novel virus in multiple infections previously missed using other methods demonstrates the usefulness of this strategy for investigating multiple infectious outbreaks, even in humans and other animals.",,"['Gao, Yuanzhu', 'Liu, Shanshan', 'Huang, Jiamiao', 'Wang, Qianqian', 'Li, Kunpeng', 'He, Jian', 'He, Jianguo', 'Weng, Shaoping', 'Zhang, Qinfen']",,,,
,PMC,MicroRNA-155 coordinates the immunological landscape within murine melanoma and correlates with immunity in human cancers,http://dx.doi.org/10.1172/jci.insight.126543,PMC6482995,,,"miR-155 has recently emerged as an important promoter of antitumor immunity through its functions in T lymphocytes. However, the impact of T cell–expressed miR-155 on immune cell dynamics in solid tumors remains unclear. In the present study, we used single-cell RNA sequencing to define the CD45(+) immune cell populations at different time points within B16F10 murine melanoma tumors growing in either wild-type or miR-155 T cell conditional knockout (TCKO) mice. miR-155 was required for optimal T cell activation and reinforced the T cell response at the expense of infiltrating myeloid cells. Further, myeloid cells from tumors growing in TCKO mice were defined by an increase in wound healing genes and a decreased IFN-γ–response gene signature. Finally, we found that miR-155 expression predicted a favorable outcome in human melanoma patients and was associated with a strong immune signature. Moreover, gene expression analysis of The Cancer Genome Atlas (TCGA) data revealed that miR-155 expression also correlates with an immune-enriched subtype in 29 other human solid tumors. Together, our study provides an unprecedented analysis of the cell types and gene expression signatures of immune cells within experimental melanoma tumors and elucidates the role of miR-155 in coordinating antitumor immune responses in mammalian tumors.",,"['Ekiz, H. Atakan', 'Huffaker, Thomas B.', 'Grossmann, Allie H.', 'Stephens, W. Zac', 'Williams, Matthew A.', 'Round, June L.', 'O’Connell, Ryan M.']",,,,
,PMC,Diverse approaches to preventing occupational tuberculosis in health workers: cross-disciplinary or cross purposes?,http://dx.doi.org/10.5588/pha.18.0086,PMC6436492,,,,,"['Ehrlich, R.', 'Spiegel, J.', 'Yassi, A.']",,,,
,PMC,利用CRISPR/Cas9技术构建敲除G6PD基因c.392G>T (p.131G>V)突变位点的HEK293T稳定细胞株,http://dx.doi.org/10.12122/j.issn.1673-4254.2019.03.10,PMC6765671,,,"OBJECTIVE: To establish a stable HEK293T cell line with c.392G>T (p.131G>V) mutation site knockout in G6PD gene using CRISPR/Cas9 technique. METHODS: We designed 4 pairs of small guide RNA (sgRNA) for G6PD c.392G>T(p.131G>V) mutation site, and constructed exogenous PX458 plasmids expressing Cas9-sgRNA. The plasmids were transfected into HEK293T cells, and the cells expressing GFP fluorescent protein were separated by flow cytometry for further culture. After verification of the knockout efficiency using T7 endonuclease Ⅰ, the monoclonal cells were screened by limiting dilution and DNA sequencing to confirm the knockout. We detected the expressions of G6PD mRNA and protein and examined functional changes of the genetically modified cells. RESULTS: We successfully constructed the Cas9-sgRNA exogenous PX458 plasmid based on the c.392G>T(p.131G>V) mutation site of G6PD gene. The editing efficiency of the 4 pairs of sgRNA, as detected by T7E1 enzyme digestion, was 6.74%, 12.36%, 12.54% and 2.94%. Sanger sequencing confirmed that the HEK293T cell line with stable knockout of G6PD c.392G>T(p.131G>V) was successfully constructed. The genetically modified cells expressed lower levels of G6PD mRNA and G6PD protein and showed reduced G6PD enzyme activity and proliferative capacity and increased apoptosis in response to vitamin K3 treatment. CONCLUSION: We successfully constructed a stable HEK293T cell model with G6PD gene c.392G>T(p.131G>V) mutation site knockout to facilitate future study of gene repair.",,"[None, None, None, None, None]",,,,
,PMC,Influence of the intestinal microbiota on disease susceptibility in kittens with experimentally-induced carriage of atypical enteropathogenic Escherichia coli.,http://dx.doi.org/10.1016/j.vetmic.2019.03.020,PMC6532395,,,"Typical enteropathogenic E. coli (tEPEC) carries the highest hazard of death in children with diarrhea and atypical EPEC (aEPEC) was recently identified as significantly associated with diarrheal mortality in kittens. In both children and kittens there is a significant association between aEPEC burden and diarrheal disease, however the infection can be found in individuals with and without diarrhea. It remains unclear to what extent, under what conditions, or by what mechanisms aEPEC serves as a primary pathogen in individuals with diarrhea. It seems likely that a combination of host and bacterial factors enable aEPEC to cause disease in some individuals and not in others. The purpose of this study was to determine the impact of aEPEC on intestinal function and diarrhea in kittens following experimentally-induced carriage and the influence of a disrupted intestinal microbiota on disease susceptibility. Results of this study identify aEPEC as a potential pathogen in kittens. In the absence of disruption to the intestinal microbiota, kittens are resistant to clinical signs of aEPEC carriage but demonstrate significant occult changes in intestinal absorption and permeability. Antibiotic-induced disruption of the intestinal microbiota prior to infection increases subsequent intestinal water loss as determined by % fecal wet weight. Enrichment of the intestinal microbiota with a commensal member of the feline mucosa-associated microbiota, Enterococcus hirae, ameliorated the effects of aEPEC experimental infection on intestinal function and water loss. These observations begin to unravel the mechanisms by which aEPEC infection may be able to exploit susceptible hosts.",,"['Watson, Victoria E.', 'Jacob, Megan E.', 'Bruno-Bárcena, José M.', 'Amirsultan, Sophia', 'Stauffer, Stephen H.', 'Píqueras, Victoria O.', 'Frias, Rafael', 'Gookin, Jody L.']",,,,
,PMC,Fatty Liver Caused by Glycogen Storage Disease Type IX: A Small Series of Cases in Children,http://dx.doi.org/10.1159/000496571,PMC6876595,,,"BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) affecting children and adolescents has increased dramatically in recent years. This increase is most probably related to the obesity pandemic and the high consumption of fructose. However, hepatic steatosis has some rare causes (e.g., some metabolic diseases) of which clinicians should be aware, particularly (but not only) when patients are non-obese or non-overweight. Differential diagnosis is notably important when pathologies have a specific treatment, such as for glycogenosis type IX (GSD-IX). AIMS: To contribute to the knowledge on the differential diagnosis of NAFLD in paediatric age and to the clinical, biochemical, molecular, and histological characterisations of GSD-IX, a rare metabolic disorder. METHODS: We performed a retrospective study of a small series of cases (n = 3) of GSD-IX diagnosed in the past 6 years, who were currently being followed up in the Units of Gastroenterology or Metabolic Diseases of the Paediatric Division of our hospital and whose clinical presentation was NAFLD in paediatric age. RESULTS: Three male patients were diagnosed with NAFLD before 2 years of age, 2 with confirmed diagnosis before the age of 3 years (alanine aminotransferase [ALT], liver ultrasound, and molecular analysis) and 1 whose diagnosis was confirmed at 11 years (ALT, liver ultrasound, liver histology, and molecular analysis). None of the patients were obese or overweight, and the daily fructose consumption was unknown. The outcome was favourable in all 3 patients, with follow-up periods ranging from 2 to 6 years. CONCLUSION: The decision on how far the search for secondary causes of NAFLD should go can be difficult, and GSD-IX must be on the list of possible causes.",,"['Leuzinger Dias, Catarina', 'Maio, Inês', 'Brandão, José Ricardo', 'Tomás, Edite', 'Martins, Esmeralda', 'Santos Silva, Ermelinda']",,,,
,PMC,Acute Respiratory Distress Syndrome,http://dx.doi.org/10.1038/s41572-019-0069-0,PMC6709677,,,"The acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients and is defined by the acute onset of noncardiogenic pulmonary edema, hypoxemia, and the need for mechanical ventilation. ARDS occurs most often in the setting of pneumonia, sepsis, aspiration of gastric contents or severe trauma, and is present in ~10% of all intensive care unit patients worldwide. Despite some improvements over the past decades, mortality remains high at 30–40% in most studies. Pathologic specimens from patients with ARDS most frequently reveal diffuse alveolar damage, and laboratory studies have demonstrated both alveolar epithelial and lung endothelial injury, resulting in accumulation of protein-rich inflammatory edema fluid in the alveolar space. Diagnosis is based on consensus syndromic criteria, with recent proposed modifications for under-resourced settings and for pediatric patients. Patient management focuses on implementing a lung-protective ventilation strategy; no specific pharmacotherapies have been identified. Long-term outcomes of patients with ARDS are increasingly recognized as important research targets, as many patients survive ARDS only to suffer ongoing functional and/or psychologic sequelae. Future directions include efforts to facilitate earlier recognition of ARDS, prognostic and/or predictive enrichment in clinical studies to identify responsive subsets, and ongoing efforts to understand fundamental mechanisms of lung injury that may respond to specific treatments.",,"['Matthay, Michael A.', 'Zemans, Rachel L.', 'Zimmerman, Guy A.', 'Arabi, Yaseen M.', 'Beitler, Jeremy R.', 'Mercat, Alain', 'Herridge, Margaret', 'Randolph, Adrienne G.', 'Calfee, Carolyn S.']",,,,
,PMC,"Abstracts of Thesis Approved for the MSc and PhD degrees at the Faculty of Medicine, Health Sciences Center, Kuwait University, Kuwait",http://dx.doi.org/10.1159/000496961,PMC6558331,,,,,,,,,
,PMC,Bacterial Outer Membrane Vesicles Provide Broad-Spectrum Protection against Influenza Virus Infection via Recruitment and Activation of Macrophages,http://dx.doi.org/10.1159/000494098,PMC6738265,,,"Influenza A virus (IAV) poses a constant worldwide threat to human health. Although conventional vaccines are available, their protective efficacy is type or strain specific, and their production is time-consuming. For the control of an influenza pandemic in particular, agents that are immediately effective against a wide range of virus variants should be developed. Although pretreatment of various Toll-like receptor (TLR) ligands have already been reported to be effective in the defense against subsequent IAV infection, the efficacy was limited to specific subtypes, and safety concerns were also raised. In this study, we investigated the protective effect of an attenuated bacterial outer membrane vesicle ­harboring modified lipid A moiety of lipopolysaccharide (fmOMV) against IAV infection and the underlying mechanisms. Administration of fmOMV conferred significant protection against a lethal dose of pandemic H1N1, PR8, H5N2, and highly pathogenic H5N1 viruses; this broad antiviral activity was dependent on macrophages but independent of neutrophils. fmOMV induced recruitment and activation of macrophages and elicited type I IFNs. Intriguingly, fmOMV showed a more significant protective effect than other TLR ligands tested in previous reports, without exhibiting any adverse effect. These results show the potential of fmOMV as a prophylactic agent for the defense against influenza virus infection.",,"['Bae, Eun-Hye', 'Seo, Sang Hwan', 'Kim, Chang-Ung', 'Jang, Min Seong', 'Song, Min-Suk', 'Lee, Tae-Young', 'Jeong, Yu-Jin', 'Lee, Moo-Seung', 'Park, Jong-Hwan', 'Lee, Pureum', 'Kim, Young Sang', 'Kim, Sang-Hyun', 'Kim, Doo-Jin']",,,,
,PMC,Virus Recognition of Glycan Receptors,http://dx.doi.org/10.1016/j.coviro.2019.01.004,PMC6476673,,,"Attachment of viruses to cell-surface receptors is the initial step in infection. Many mammalian viruses have evolved to recognize receptors that are glycans on cell-surface glycoproteins or glycolipids. Although glycans are a ubiquitous component of mammalian cells, the types of terminal structures expressed vary among different cell-types and tissues, and even between comparable cells and tissues from different species, frequently leading to specific tissue and species tropisms as a direct consequence of glycan receptor recognition. Covering the majority of known virus families, this review provides an overview of mammalian viruses that use glycans as receptors, and their roles in determining in host recognition and tropism.",,"['Thompson, Andrew J.', 'de Vries, Robert P.', 'Paulson, James C.']",,,,
,PMC,Acute Respiratory Infection in Human Dipeptidyl Peptidase 4-Transgenic Mice Infected with Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.01818-18,PMC6401458,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) infection can manifest as a mild illness, acute respiratory distress, organ failure, or death. Several animal models have been established to study disease pathogenesis and to develop vaccines and therapeutic agents. Here, we developed transgenic (Tg) mice on a C57BL/6 background; these mice expressed human CD26/dipeptidyl peptidase 4 (hDPP4), a functional receptor for MERS-CoV, under the control of an endogenous hDPP4 promoter. We then characterized this mouse model of MERS-CoV. The expression profile of hDPP4 in these mice was almost equivalent to that in human tissues, including kidney and lung; however, hDPP4 was overexpressed in murine CD3-positive cells within peripheral blood and lymphoid tissues. Intranasal inoculation of young and adult Tg mice with MERS-CoV led to infection of the lower respiratory tract and pathological evidence of acute multifocal interstitial pneumonia within 7 days, with only transient loss of body weight. However, the immunopathology in young and adult Tg mice was different. On day 5 or 7 postinoculation, lungs of adult Tg mice contained higher levels of proinflammatory cytokines and chemokines associated with migration of macrophages. These results suggest that the immunopathology of MERS-CoV infection in the Tg mouse is age dependent. The mouse model described here will increase our understanding of disease pathogenesis and host mediators that protect against MERS-CoV infection. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) infections are endemic in the Middle East and a threat to public health worldwide. Rodents are not susceptible to the virus because they do not express functional receptors; therefore, we generated a new animal model of MERS-CoV infection based on transgenic mice expressing human DPP4 (hDPP4). The pattern of hDPP4 expression in this model was similar to that in human tissues (except lymphoid tissue). In addition, MERS-CoV was limited to the respiratory tract. Here, we focused on host factors involved in immunopathology in MERS-CoV infection and clarified differences in antiviral immune responses between young and adult transgenic mice. This new small-animal model could contribute to more in-depth study of the pathology of MERS-CoV infection and aid development of suitable treatments.",,"['Iwata-Yoshikawa, Naoko', 'Okamura, Tadashi', 'Shimizu, Yukiko', 'Kotani, Osamu', 'Sato, Hironori', 'Sekimukai, Hanako', 'Fukushi, Shuetsu', 'Suzuki, Tadaki', 'Sato, Yuko', 'Takeda, Makoto', 'Tashiro, Masato', 'Hasegawa, Hideki', 'Nagata, Noriyo']",,,,
,PMC,TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection,http://dx.doi.org/10.1128/JVI.01815-18,PMC6401451,,,"Transmembrane serine protease TMPRSS2 activates the spike protein of highly pathogenic human coronaviruses such as severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV). In vitro, activation induces virus-cell membrane fusion at the cell surface. However, the roles of TMPRSS2 during coronavirus infection in vivo are unclear. Here, we used animal models of SARS-CoV and MERS-CoV infection to investigate the role of TMPRSS2. Th1-prone C57BL/6 mice and TMPRSS2-knockout (KO) mice were used for SARS-CoV infection, and transgenic mice expressing the human MERS-CoV receptor DPP4 (hDPP4-Tg mice) and TMPRSS2-KO hDPP4-Tg mice were used for MERS-CoV infection. After experimental infection, TMPRSS2-deficient mouse strains showed reduced body weight loss and viral kinetics in the lungs. Lack of TMPRSS2 affected the primary sites of infection and virus spread within the airway, accompanied by less severe immunopathology. However, TMPRSS2-KO mice showed weakened inflammatory chemokine and/or cytokine responses to intranasal stimulation with poly(I·C), a Toll-like receptor 3 agonist. In conclusion, TMPRSS2 plays a crucial role in viral spread within the airway of murine models infected by SARS-CoV and MERS-CoV and in the resulting immunopathology. IMPORTANCE Broad-spectrum antiviral drugs against highly pathogenic coronaviruses and other emerging viruses are desirable to enable a rapid response to pandemic threats. Transmembrane protease serine type 2 (TMPRSS2), a protease belonging to the type II transmembrane serine protease family, cleaves the coronavirus spike protein, making it a potential therapeutic target for coronavirus infections. Here, we examined the role of TMPRSS2 using animal models of SARS-CoV and MERS-CoV infection. The results suggest that lack of TMPRSS2 in the airways reduces the severity of lung pathology after infection by SARS-CoV and MERS-CoV. Taken together, the results will facilitate development of novel targets for coronavirus therapy.",,"['Iwata-Yoshikawa, Naoko', 'Okamura, Tadashi', 'Shimizu, Yukiko', 'Hasegawa, Hideki', 'Takeda, Makoto', 'Nagata, Noriyo']",,,,
,PMC,Tetraspanins: Architects of Viral Entry and Exit Platforms,http://dx.doi.org/10.1128/JVI.01429-17,PMC6401424,,,"Host factors render cells susceptible to viral infection. One family of susceptibility factors, the tetraspanin proteins, facilitate enveloped virus entry by promoting virus-cell membrane fusion. They also facilitate viral egress from infected cells. In this Gem, we discuss recent insights into how tetraspanins assemble viral entry and exit platforms on cell membranes, and we speculate that tetraspanins contribute to nonviral membrane fusions by similar mechanisms.",,"['Hantak, Michael P.', 'Qing, Enya', 'Earnest, James T.', 'Gallagher, Tom']",,,,
,PMC,Functional and Physical Interaction between the Arf Activator GBF1 and Hepatitis C Virus NS3 Protein,http://dx.doi.org/10.1128/JVI.01459-18,PMC6401423,,,"GBF1 has emerged as a host factor required for the genome replication of RNA viruses of different families. During the hepatitis C virus (HCV) life cycle, GBF1 performs a critical function at the onset of genome replication but is dispensable when the replication is established. To better understand how GBF1 regulates HCV infection, we have looked for interactions between GBF1 and HCV proteins. NS3 was found to interact with GBF1 in yeast two-hybrid, coimmunoprecipitation, and proximity ligation assays and to interfere with GBF1 function and alter GBF1 intracellular localization in cells expressing NS3. The interaction was mapped to the Sec7 domain of GBF1 and the protease domain of NS3. A reverse yeast two-hybrid screen to identify mutations altering NS3-GBF1 interaction yielded an NS3 mutant (N77D, Con1 strain) that is nonreplicative despite conserved protease activity and does not interact with GBF1. The mutated residue is exposed at the surface of NS3, suggesting it is part of the domain of NS3 that interacts with GBF1. The corresponding mutation in strain JFH-1 (S77D) produces a similar phenotype. Our results provide evidence for an interaction between NS3 and GBF1 and suggest that an alteration of this interaction is detrimental to HCV genome replication. IMPORTANCE Single-stranded, positive-sense RNA viruses rely to a significant extent on host factors to achieve the replication of their genome. GBF1 is such a cellular protein that is required for the replication of several RNA viruses, but its mechanism of action during viral infections is not yet defined. In this study, we investigated potential interactions that GBF1 might engage in with proteins of HCV, a GBF1-dependent virus. We found that GBF1 interacts with NS3, a nonstructural protein involved in HCV genome replication, and our results suggest that this interaction is important for GBF1 function during HCV replication. Interestingly, GBF1 interaction with HCV appears different from its interaction with enteroviruses, another group of GBF1-dependent RNA viruses, in keeping with the fact that HCV and enteroviruses use different functions of GBF1.",,"['Lebsir, Nadjet', 'Goueslain, Lucie', 'Farhat, Rayan', 'Callens, Nathalie', 'Dubuisson, Jean', 'Jackson, Catherine L.', 'Rouillé, Yves']",,,,
,PMC,GII.4 Norovirus Protease Shows pH-Sensitive Proteolysis with a Unique Arg-His Pairing in the Catalytic Site,http://dx.doi.org/10.1128/JVI.01479-18,PMC6401421,,,"Human noroviruses (NoVs) are the main cause of epidemic and sporadic gastroenteritis. Phylogenetically, noroviruses are divided into seven genogroups, with each divided into multiple genotypes. NoVs belonging to genogroup II and genotype 4 (GII.4) are globally most prevalent. Genetic diversity among the NoVs and the periodic emergence of novel strains present a challenge for the development of vaccines and antivirals to treat NoV infection. NoV protease is essential for viral replication and is an attractive target for the development of antivirals. The available structure of GI.1 protease provided a basis for the design of inhibitors targeting the active site of the protease. These inhibitors, although potent against the GI proteases, poorly inhibit the GII proteases, for which structural information is lacking. To elucidate the structural basis for this difference in the inhibitor efficiency, we determined the crystal structure of a GII.4 protease. The structure revealed significant changes in the S2 substrate-binding pocket, making it noticeably smaller, and in the active site, with the catalytic triad residues showing conformational changes. Furthermore, a conserved arginine is found inserted into the active site, interacting with the catalytic histidine and restricting substrate/inhibitor access to the S2 pocket. This interaction alters the relationships between the catalytic residues and may allow for a pH-dependent regulation of protease activity. The changes we observed in the GII.4 protease structure may explain the reduced potency of the GI-specific inhibitors against the GII protease and therefore must be taken into account when designing broadly cross-reactive antivirals against NoVs. IMPORTANCE Human noroviruses (NoVs) cause sporadic and epidemic gastroenteritis worldwide. They are divided into seven genogroups (GI to GVII), with each genogroup further divided into several genotypes. Human NoVs belonging to genogroup II and genotype 4 (GII.4) are the most prevalent. Currently, there are no vaccines or antiviral drugs available for NoV infection. The protease encoded by NoV is considered a valuable target because of its essential role in replication. NoV protease structures have only been determined for the GI genogroup. We show here that the structure of the GII.4 protease exhibits several significant changes from GI proteases, including a unique pairing of an arginine with the catalytic histidine that makes the proteolytic activity of GII.4 protease pH sensitive. A comparative analysis of NoV protease structures may provide a rational framework for structure-based drug design of broadly cross-reactive inhibitors targeting NoVs.",,"['Viskovska, Mariya A.', 'Zhao, Boyang', 'Shanker, Sreejesh', 'Choi, Jae-Mun', 'Deng, Lisheng', 'Song, Yongchen', 'Palzkill, Timothy', 'Hu, Liya', 'Estes, Mary K.', 'Venkataram Prasad, B. V.']",,,,
,PMC,CME Tropical Medicine (123847): self-assessment questionnaire,http://dx.doi.org/10.7861/clinmedicine.19-2-161,PMC6454372,,,,,"Chowdhury, Tahseen A",,,,
,PMC,Outbreak science: recent progress in the detection and response to outbreaks of infectious diseases,http://dx.doi.org/10.7861/clinmedicine.19-2-140,PMC6454359,,,"The frequency of reported outbreaks of infectious diseases has increased over the past 3 decades, with predictions that this rise will continue. Outbreak response continues to follow nine basic principles: establish the presence of an outbreak, verify the diagnosis, make a case definition, find cases and contacts, conduct basic epidemiology, test hypotheses, institute control measures, communicate the situation and establish ongoing surveillance. Within each of these areas, significant advances have been made over the past 5 years using progress in digital, laboratory, epidemiology and anthropological equipment or techniques. Irrespective of these, future outbreaks of high-consequence are inevitable, and vigilance and preparation must continue in order to prevent significant mortality, morbidity and socio-economic crisis.",,"['Houlihan, Catherine F', 'Whitworth, James AG']",,,,
,PMC,Middle East respiratory syndrome coronavirus (MERS-CoV): A review,http://dx.doi.org/10.18683/germs.2019.1155,PMC6446491,,,"As a novel coronavirus first reported by Saudi Arabia in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) is responsible for an acute human respiratory syndrome. The virus, of 2C beta-CoV lineage, expresses the dipeptidyl peptidase 4 (DPP4) receptor and is densely endemic in dromedary camels of East Africa and the Arabian Peninsula. MERS-CoV is zoonotic but human-to-human transmission is also possible. Surveillance and phylogenetic researches indicate MERS-CoV to be closely associated with bats’ coronaviruses, suggesting bats as reservoirs, although unconfirmed. With no vaccine currently available for MERS-CoV nor approved prophylactics, its global spread to over 25 countries with high fatalities highlights its role as ongoing public health threat. An articulated action plan ought to be taken, preferably from a One Health perspective, for appropriately advanced countermeasures against MERS-CoV.",,"['Ramadan, Nour', 'Shaib, Houssam']",,,,
,PMC,Quality Assurance Sampling Plans in US Stockpiles for Personal Protective Equipment,http://dx.doi.org/10.1089/hs.2018.0133,PMC6712566,,,"Personal protective equipment (PPE) stockpiles in the United States were established to facilitate rapid deployment of medical assets to sites affected by public health emergencies. Large quantities of PPE were introduced into US stockpiles because of the need to protect healthcare and other professionals during these events. Because most stockpiled PPE was acquired during, or immediately following, large-scale public health events, such as pandemic influenza planning (2005-2008), SARS (2003), H1N1 (2009-10), and Ebola (2014-15), aging PPE poses a significant problem. PPE such as N95 filtering face piece respirators were not designed to be stored for long periods, and much of the currently stored PPE has exceeded its manufacturer-assigned shelf life. Given the significant investment in the procurement and storage of PPE, along with projections of consumption during public health emergencies, discarding large quantities of potentially viable PPE is not an attractive option. Although shelf-life extension programs exist for other stockpiled medical assets, no such option is currently available for stockpiled PPE. This article posits stockpile quality assurance sampling plans as a mechanism through which shelf-life extension programs for stockpiled PPE may be achieved. We discuss some of the nuances that should be considered when developing a plan tailored to stockpiles and provide basic decision tools that may be used in the context of a quality assurance program tailored to stockpiled PPE. We also explore basic information by comparing and contrasting different sample size options.",,"['Yorio, Patrick L.', 'Rottach, Dana R.', 'Dubaniewicz, Mitchell']",,,,
,PMC,Implementation framework for One Health approach,http://dx.doi.org/10.4103/ijmr.IJMR_1517_18,PMC6607818,31249197,CC BY-NC-SA,,2019 Mar,"Bhatia, Rajesh",Indian J Med Res,,,
,PMC,PCR Prevalence of Murine Opportunistic Microbes and their Mitigation by Using Vaporized Hydrogen Peroxide,http://dx.doi.org/10.30802/AALAS-JAALAS-18-000112,PMC6433363,,,"Exposing immunodeficient mice to opportunistic microbes introduces risks of data variability, morbidity, mortality, and the invalidation of studies involving unique human reagents, including the loss of primary human hematopoietic cells, patient-derived xenografts, and experimental therapeutics. The prevalence of 15 opportunistic microbes in a murine research facility was determined by yearlong PCR-based murine and IVC equipment surveillance comprising 1738 specimens. Of the 8 microbes detected, 3 organisms—Staphylococcus xylosus, Proteus mirabilis, and Pasteurella pneumotropica biotype Heyl—were most prevalent in both murine and IVC exhaust plenum specimens. Overall, the 8 detectable microbes were more readily PCR-detectable in IVC exhaust airways than in murine specimens, supporting the utility of PCR testing of IVC exhaust airways as a component of immunodeficient murine health surveillance. Vaporized hydrogen peroxide (VHP) exposure of IVC equipment left unassembled (that is, in a ‘static-open’ configuration) did not eliminate PCR detectable evidence of microbes. In contrast, VHP exposure of IVC equipment assembled ‘active-closed’ eliminated PCR-detectable evidence of all microbes. Ensuring data integrity and maintaining a topographically complex immunodeficient murine research environment is facilitated by knowing the prevalent opportunistic microbes to be monitored and by implementing a PCR-validated method of facility decontamination that mitigates opportunistic microbes and the risk of invalidation of studies involving immunodeficient mice.",,"['Ragland, Natalie H', 'Miedel, Emily L', 'Engelman, Robert W']",,,,
,PMC,Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting,http://dx.doi.org/10.3791/59010,PMC6677141,,,"The protocol aims to generate coronavirus (CoV) spike (S) fusion protein pseudotyped particles with a murine leukemia virus (MLV) core and luciferase reporter, using a simple transfection procedure of the widely available HEK-293T cell line. Once formed and released from producer cells, these pseudovirions incorporate a luciferase reporter gene. Since they only contain the heterologous coronavirus spike protein on their surface, the particles behave like their native coronavirus counterparts for entry steps. As such, they are the excellent surrogates of native virions for studying viral entry into host cells. Upon successful entry and infection into target cells, the luciferase reporter gets integrated into the host cell genome and is expressed. Using a simple luciferase assay, transduced cells can be easily quantified. An important advantage of the procedure is that it can be performed in biosafety level 2 (BSL-2) facilities instead of BSL-3 facilities required for work with highly pathogenic coronaviruses such as Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Another benefit comes from its versatility as it can be applied to envelope proteins belonging to all three classes of viral fusion proteins, such as the class I influenza hemagglutinin (HA) and Ebola virus glycoprotein (GP), the class II Semliki forest virus El protein, or the class III vesicular stomatitis virus G glycoprotein. A limitation of the methodology is that it can only recapitulate virus entry steps mediated by the envelope protein being investigated. For studying other viral life cycle steps, other methods are required. Examples of the many applications these pseudotype particles can be used in include investigation of host cell susceptibility and tropism and testing the effects of virus entry inhibitors to dissect viral entry pathways used.",,"['Millet, Jean K.', 'Tang, Tiffany', 'Nathan, Lakshmi', 'Jaimes, Javier A.', 'Hsu, Hung-Lun', 'Daniel, Susan', 'Whittaker, Gary R.']",,,,
,PMC,Guild-level responses of bats to habitat conversion in a lowland Amazonian rainforest: species composition and biodiversity,http://dx.doi.org/10.1093/jmammal/gyz023,PMC6394116,,,"Landscape modification represents one of the most severe threats to biodiversity from local to global scales. Conversion of forest to agricultural production generally results in patches of habitat that subdivide or isolate populations, alter the behavior of species, modify interspecific interactions, reduce biodiversity, and compromise ecosystem processes. Moreover, conversion may increase exposure of humans to zoonoses to which they would otherwise rarely be exposed. We evaluated the effects of forest conversion to agriculture, and its subsequent successional dynamics, on bat communities in a region of the Amazon that was predominantly closed-canopy rainforest. Based on a nonmanipulative experiment, we quantified differences in species composition, community structure, and taxonomic biodiversity among closed-canopy forest (bosque), agricultural lands (chacra), and secondary forest (purma) for two phyllostomid guilds (frugivores and gleaning animalivores) during the wet and dry seasons. Responses were complex and guild-specific. For frugivores, species composition (species abundance distributions) differed between all possible pairs of habitats in both wet and dry seasons. For gleaning animalivores, species composition differed between all possible pairs of habitats in the dry season, but no differences characterized the wet season. Ecological structure (rank abundance distributions) differed among habitats in guild-specific and season-specific manners. For frugivores, mean diversity, evenness, and dominance were greater in bosque than in purma; mean dominance was greater in bosque than in chacra, but local rarity was greater in chacra than in bosque, and no differences were manifest between purma and chacra. For gleaning animalivores, mean diversity and evenness were greater in bosque than in purma, but no differences were manifest between chacra and bosque, or between purma and chacra. Such results have important implications for management, conservation, and the epidemiology of zoonotic diseases. La actual modificación del paisaje, a escalas que van de lo local a lo global, es una de las amenazas más severas a la biodiversidad. De manera general, la conversión de bosques a áreas agrícolas produce parches de hábitat que subdividen o aíslan poblaciones, alteran la conducta de las especies, modifican las interacciones interespecíficas, reducen la biodiversidad y comprometen las funciones de los ecosistemas. Más aún, la transformación de estos ambientes puede incrementar la probabilidad de que las poblaciones humanas interactúen con zoonosis con las que de otra manera raramente entrarían en contacto. Evaluamos los efectos de la conversión de hábitat en comunidades de murciélagos en una región de Amazonia en la que la vegetación dominante es un bosque lluvioso de copas cerradas, y en la cual los efectos de la conversión a usos agrícolas sobre la biodiversidad, y la subsecuente dinámica sucesional, son aún poco comprendidos. Por medio de un experimento no-manipulativo, cuantificamos las diferencias en composición de especies, estructura de la comunidad y diversidad taxonómica entre bosque cerrado (bosque), áreas agrícolas (chacra) y bosque secundario (purma) para dos gremios tróficos de murciélagos filostómidos (frugívoros y forrajeadores de sustrato) durante dos temporadas (secas y lluvias). Las respuestas fueron complejas y diferentes para cada gremio. Para los frugívoros, la composición de especies (distribución de las abundancias) fue diferente para todos los posibles pares de hábitats tanto para secas como para lluvias. Para los forrajeadores de sustrato, la composición de especies difirió entre todos los posibles pares de hábitats en la temporada seca, pero no en la de lluvias. La estructura ecológica (distribuciones rango-abundancia) fue también específica para gremios y temporadas. Para los frugívoros, la diversidad promedio, equidad y dominancia fueron mayores en bosque que en purma; la dominancia promedio fue mayor en bosque que en chacra, pero la rareza local fue mayor en chacra que en bosque, y no se encontraron diferencias entre purma y chacra. Para los forrajeadores de sustrato, la diversidad promedio y la dominancia fueron mayores en bosque que en purma, pero no se detectaron diferencias entre chacra y bosque, o entre purma y chacra. Estos resultados tienen importantes implicaciones para el manejo, conservación y epidemiología de zoonosis.",,"['Willig, Michael R', 'Presley, Steven J', 'Plante, Jean-Luc', 'Bloch, Christopher P', 'Solari, Sergio', 'Pacheco, Victor', 'Weaver, Scott C']",,,,
,PMC,IL-1 receptor antagonist therapy mitigates placental dysfunction and perinatal injury following Zika virus infection,http://dx.doi.org/10.1172/jci.insight.122678,PMC6483652,,,"Zika virus (ZIKV) infection during pregnancy causes significant adverse sequelae in the developing fetus, and results in long-term structural and neurologic defects. Most preventive and therapeutic efforts have focused on the development of vaccines, antivirals, and antibodies. The placental immunologic response to ZIKV, however, has been largely overlooked as a target for therapeutic intervention. The placental inflammatory response, specifically IL-1β secretion and signaling, is induced by ZIKV infection and represents an environmental factor that is known to increase the risk of perinatal developmental abnormalities. We show in a mouse model that maternally administrated IL-1 receptor antagonist (IRA; Kineret, or anakinra), following ZIKV exposure, can preserve placental function (by improving trophoblast invasion and placental vasculature), increase fetal viability, and reduce neurobehavioral deficits in the offspring. We further demonstrate that while ZIKV RNA is highly detectable in placentas, it is not correlated with fetal viability. Beyond its effects in the placenta, we show that IL-1 blockade may also directly decrease fetal neuroinflammation by mitigating fetal microglial activation in a dose-dependent manner. Our studies distinguish the role of placental inflammation during ZIKV-infected pregnancies, and demonstrate that maternal IRA may attenuate fetal neuroinflammation and improve perinatal outcomes.",,"['Lei, Jun', 'Vermillion, Meghan S.', 'Jia, Bei', 'Xie, Han', 'Xie, Li', 'McLane, Michael W.', 'Sheffield, Jeanne S.', 'Pekosz, Andrew', 'Brown, Amanda', 'Klein, Sabra L.', 'Burd, Irina']",,,,
,PMC,A Vesicular Stomatitis Virus-Based Vaccine Carrying Zika Virus Capsid Protein Protects Mice from Viral Infection,http://dx.doi.org/10.1007/s12250-019-00083-7,PMC6420591,,,,,"['Shi, Xiaodan', 'Hu, Jingping', 'Guo, Jing', 'Wu, Chuanjian', 'Xiong, Sidong', 'Dong, Chunsheng']",,,,
,PMC,Correction to: Genetic Evidence of Middle East Respiratory Syndrome Coronavirus (MERS-Cov) and Widespread Seroprevalence among Camels in Kenya,http://dx.doi.org/10.1007/s12250-019-00092-6,PMC6420511,,,,,"['Ommeh, Sheila', 'Zhang, Wei', 'Zohaib, Ali', 'Chen, Jing', 'Zhang, Huajun', 'Hu, Ben', 'Ge, Xing-Yi', 'Yang, Xing-Lou', 'Masika, Moses', 'Obanda, Vincent', 'Luo, Yun', 'Li, Shan', 'Waruhiu, Cecilia', 'Li, Bei', 'Zhu, Yan', 'Ouma, Desterio', 'Odendo, Vincent', 'Wang, Lin-Fa', 'Anderson, Danielle E.', 'Lichoti, Jacqueline', 'Mungube, Erick', 'Gakuya, Francis', 'Zhou, Peng', 'Ngeiywa, Kisa-Juma', 'Yan, Bing', 'Agwanda, Bernard', 'Shi, Zheng-Li']",,,,
,PMC,Endonuclease Activity Inhibition of the NS1 Protein of Parvovirus B19 as a Novel Target for Antiviral Drug Development,http://dx.doi.org/10.1128/AAC.01879-18,PMC6395930,,,"Human parvovirus B19 (B19V), a member of the genus Erythroparvovirus of the family Parvoviridae, is a small nonenveloped virus that has a single-stranded DNA (ssDNA) genome of 5.6 kb with two inverted terminal repeats (ITRs). B19V infection often results in severe hematological disorders and fetal death in humans. B19V replication follows a model of rolling hairpin-dependent DNA replication, in which the large nonstructural protein NS1 introduces a site-specific single-strand nick in the viral DNA replication origins, which locate at the ITRs. NS1 executes endonuclease activity through the N-terminal origin-binding domain. Nicking of the viral replication origin is a pivotal step in rolling hairpin-dependent viral DNA replication. Here, we developed a fluorophore-based in vitro nicking assay of the replication origin using the origin-binding domain of NS1 and compared it with the radioactive in vitro nicking assay. We used both assays to screen a set of small-molecule compounds (n = 96) that have potential antinuclease activity. We found that the fluorophore-based in vitro nicking assay demonstrates sensitivity and specificity values as high as those of the radioactive assay. Among the 96 compounds, we identified 8 which have an inhibition of >80% at 10 µM in both the fluorophore-based and radioactive in vitro nicking assays. We further tested 3 compounds that have a flavonoid-like structure and an in vitro 50% inhibitory concentration that fell in the range of 1 to 3 µM. Importantly, they also exhibited inhibition of B19V DNA replication in UT7/Epo-S1 cells and ex vivo-expanded human erythroid progenitor cells.",,"['Xu, Peng', 'Ganaie, Safder S.', 'Wang, Xiaomei', 'Wang, Zekun', 'Kleiboeker, Steve', 'Horton, Nancy C.', 'Heier, Richard F.', 'Meyers, Marvin J.', 'Tavis, John E.', 'Qiu, Jianming']",,,,
,PMC,LncRNA PRINS is involved in the development of nephropathy in patients with diabetes via interaction with Smad7,http://dx.doi.org/10.3892/etm.2019.7307,PMC6434383,,,"Long non-coding RNA psoriasis-susceptibilityrelated RNA gene induced by stress (PRINS) is known to be involved in kidney ischemia reperfusion injury. The aim of the current study was to investigate the potential role of PRINS in diabetic nephropathy. The relative mRNA expression level of PRINS and SMAD family member 7 (Smad7) was examined in patients with diabetes, including patients without obvious complications (n=43), patients with diabetic nephropathy (n=33), diabetic retinopathy (n=37), diabetic cardiomyopathy (n=29), diabetic lung disease (n=38) and healthy controls (n=48). Correlation analysis between the expression level of PRINS and Smad7 was analyzed by Pearson's correlation analysis. In addition, overexpression of PRINS was confirmed in mouse podocyte cells and cell viability and Smad7 protein expression was detected by MTT assay and western blot analysis, respectively. The expression levels of PRINS and Smad7 were significantly increased in patients with diabetes compared with healthy controls. In addition, the expression levels of PRINS and Smad7 were significantly increased in patients with diabetic nephropathy compared with other diabetic complications. The expression level of PRINS in mouse podocyte cells was upregulated following treatment with high glucose. A significant positive correlation between the expression level of PRINS and Smad7 was observed in patients with diabetic nephropathy. However, there was no correlation was observed in other patient groups compared with healthy controls. Overexpression of PRINS decreased the viability of mouse podocyte cells and enhanced Smad7 protein expression. Taken together, these results suggest that PRINS may be involved in the development of nephropathy in patients with diabetes.",,"['Jiao, Haiyan', 'Xie, Daolin', 'Qiao, Yanhong']",,,,
,PMC,Anti–spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection,http://dx.doi.org/10.1172/jci.insight.123158,PMC6478436,,,"Newly emerging viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle Eastern respiratory syndrome CoVs (MERS-CoV), and H7N9, cause fatal acute lung injury (ALI) by driving hypercytokinemia and aggressive inflammation through mechanisms that remain elusive. In SARS-CoV/macaque models, we determined that anti–spike IgG (S-IgG), in productively infected lungs, causes severe ALI by skewing inflammation-resolving response. Alveolar macrophages underwent functional polarization in acutely infected macaques, demonstrating simultaneously both proinflammatory and wound-healing characteristics. The presence of S-IgG prior to viral clearance, however, abrogated wound-healing responses and promoted MCP1 and IL-8 production and proinflammatory monocyte/macrophage recruitment and accumulation. Critically, patients who eventually died of SARS (hereafter referred to as deceased patients) displayed similarly accumulated pulmonary proinflammatory, absence of wound-healing macrophages, and faster neutralizing antibody responses. Their sera enhanced SARS-CoV–induced MCP1 and IL-8 production by human monocyte–derived wound-healing macrophages, whereas blockade of FcγR reduced such effects. Our findings reveal a mechanism responsible for virus-mediated ALI, define a pathological consequence of viral specific antibody response, and provide a potential target for treatment of SARS-CoV or other virus-mediated lung injury.",,"['Liu, Li', 'Wei, Qiang', 'Lin, Qingqing', 'Fang, Jun', 'Wang, Haibo', 'Kwok, Hauyee', 'Tang, Hangying', 'Nishiura, Kenji', 'Peng, Jie', 'Tan, Zhiwu', 'Wu, Tongjin', 'Cheung, Ka-Wai', 'Chan, Kwok-Hung', 'Alvarez, Xavier', 'Qin, Chuan', 'Lackner, Andrew', 'Perlman, Stanley', 'Yuen, Kwok-Yung', 'Chen, Zhiwei']",,,,
,PMC,Porcine Hemagglutinating Encephalomyelitis Virus Activation of the Integrin α5β1-FAK-Cofilin Pathway Causes Cytoskeletal Rearrangement To Promote Its Invasion of N2a Cells,http://dx.doi.org/10.1128/JVI.01736-18,PMC6384086,,,"Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic virus that causes diffuse neuronal infection with neurological damage and high mortality. Virus-induced cytoskeletal dynamics are thought to be closely related to this type of nerve damage. Currently, the regulation pattern of the actin cytoskeleton and its molecular mechanism remain unclear when PHEV enters the host cells. Here, we demonstrate that entry of PHEV into N2a cells induces a biphasic remodeling of the actin cytoskeleton and a dynamic change in cofilin activity. Viral entry is affected by the disruption of actin kinetics or alteration of cofilin activity. PHEV binds to integrin α5β1 and then initiates the integrin α5β1-FAK signaling pathway, leading to virus-induced early cofilin phosphorylation and F-actin polymerization. Additionally, Ras-related C3 botulinum toxin substrate 1 (Rac1), cell division cycle 42 (Cdc42), and downstream regulatory gene p21-activated protein kinases (PAKs) are recruited as downstream mediators of PHEV-induced dynamic changes of the cofilin activity pathway. In conclusion, we demonstrate that PHEV utilizes the integrin α5β1-FAK-Rac1/Cdc42-PAK-LIMK-cofilin pathway to cause an actin cytoskeletal rearrangement to promote its own invasion, providing theoretical support for the development of PHEV pathogenic mechanisms and new antiviral targets. IMPORTANCE PHEV, a member of the Coronaviridae family, is a typical neurotropic virus that primarily affects the nervous system of piglets to produce typical neurological symptoms. However, the mechanism of nerve damage caused by the virus has not been fully elucidated. Actin is an important component of the cytoskeleton of eukaryotic cells and serves as the first obstacle to the entry of pathogens into host cells. Additionally, the morphological structure and function of nerve cells depend on the dynamic regulation of the actin skeleton. Therefore, exploring the mechanism of neuronal injury induced by PHEV from the perspective of the actin cytoskeleton not only helps elucidate the pathogenesis of PHEV but also provides a theoretical basis for the search for new antiviral targets. This is the first report to define a mechanistic link between alterations in signaling from cytoskeleton pathways and the mechanism of PHEV invading nerve cells.",,"['Lv, Xiaoling', 'Li, Zi', 'Guan, Jiyu', 'Hu, Shiyu', 'Zhang, Jing', 'Lan, Yungang', 'Zhao, Kui', 'Lu, Huijun', 'Song, Deguang', 'He, Hongbin', 'Gao, Feng', 'He, Wenqi']",,,,
,PMC,"Evolution of Hepatitis B Virus Receptor NTCP Reveals Differential Pathogenicities and Species Specificities of Hepadnaviruses in Primates, Rodents, and Bats",http://dx.doi.org/10.1128/JVI.01738-18,PMC6384064,,,"Human hepatitis B virus (HBV) is a global health problem, affecting more than 250 million people worldwide. HBV-like viruses, named orthohepadnaviruses, also naturally infect nonhuman primates, rodents, and bats, but their pathogenicity and evolutionary history are unclear. Here, we determined the evolutionary history of the HBV receptors NTCP and GPC5 over millions of years of primate, rodent, and bat evolution. We use this as a proxy to understand the pathogenicity of orthohepadnaviruses in mammalian hosts and to determine the implications for species specificity. We found that NTCP, but not GPC5, has evolved under positive selection in primates (27 species), rodents (18 species), and bats (21 species) although at distinct residues. Notably, the positively selected codons map to the HBV-binding sites in primate NTCP, suggesting past genetic “arms races” with pathogenic orthohepadnaviruses. In rodents, the positively selected codons fall outside and within the presumed HBV-binding sites, which may contribute to the restricted circulation of rodent orthohepadnaviruses. In contrast, the presumed HBV-binding motifs in bat NTCP are conserved, and none of the positively selected codons map to this region. This suggests that orthohepadnaviruses may bind to different surfaces in bat NTCP. Alternatively, the patterns may reflect adaptive changes associated with metabolism rather than pathogens. Overall, our findings further point to NTCP as a naturally occurring genetic barrier for cross-species transmissions in primates, which may contribute to the narrow host range of HBV. In contrast, this constraint seems less important in bats, which may correspond to greater orthohepadnavirus circulation and diversity. IMPORTANCE Chronic infection with hepatitis B virus (HBV) is a major cause of liver disease and cancer in humans. Mammalian HBV-like viruses are also found in nonhuman primates, rodents, and bats. As for most viruses, HBV requires a successful interaction with a host receptor for replication. Cellular receptors are thus key determinants of host susceptibility as well as specificity. One hallmark of pathogenic virus-host relationships is the reciprocal evolution of host receptor and viral envelope proteins, as a result of their antagonistic interaction over time. The dynamics of these so-called “evolutionary arms races” can leave signatures of adaptive selection, which in turn reveal the evolutionary history of the virus-host interaction as well as viral pathogenicity and the genetic determinants of species specificity. Here, we show how HBV-like viruses have shaped the evolutionary history of their mammalian host receptor, as a result of their ancient pathogenicity, and decipher the genetic determinants of cross-species transmissions.",,"['Jacquet, Stéphanie', 'Pons, Jean-Baptiste', 'De Bernardo, Ariel', 'Ngoubangoye, Barthélémy', 'Cosset, François-Loic', 'Régis, Corinne', 'Etienne, Lucie', 'Pontier, Dominique']",,,,
,PMC,Porcine Intestinal Enteroids: a New Model for Studying Enteric Coronavirus Porcine Epidemic Diarrhea Virus Infection and the Host Innate Response,http://dx.doi.org/10.1128/JVI.01682-18,PMC6384061,,,"Porcine epidemic diarrhea virus (PEDV), a member of the group of alphacoronaviruses, is the pathogen of a highly contagious gastrointestinal swine disease. The elucidation of the events associated with the intestinal epithelial response to PEDV infection has been limited by the absence of good in vitro porcine intestinal models that recapitulate the multicellular complexity of the gastrointestinal tract. Here, we generated swine enteroids from the intestinal crypt stem cells of the duodenum, jejunum, or ileum and found that the generated enteroids are able to satisfactorily recapitulate the complicated intestinal epithelium in vivo and are susceptible to infection by PEDV. PEDV infected multiple types of cells, including enterocytes, stem cells, and goblet cells, and exhibited segmental infection discrepancies compared with ileal enteroids and colonoids, and this finding was verified in vivo. Moreover, the clinical isolate PEDV-JMS propagated better in ileal enteroids than the cell-adapted isolate PEDV-CV777, and PEDV infection suppressed interferon (IFN) production early during the infection course. IFN lambda elicited a potent antiviral response and inhibited PEDV in enteroids more efficiently than IFN alpha (IFN-α). Therefore, swine enteroids provide a novel in vitro model for exploring the pathogenesis of PEDV and for the in vitro study of the interplay between a host and a variety of swine enteric viruses. IMPORTANCE PEDV is a highly contagious enteric coronavirus that causes significant economic losses, and the lack of a good in vitro model system is a major roadblock to an in-depth understanding of PEDV pathogenesis. Here, we generated a porcine intestinal enteroid model for PEDV infection. Utilizing porcine intestinal enteroids, we demonstrated that PEDV infects multiple lineages of the intestinal epithelium and preferably infects ileal enteroids over colonoids and that enteroids prefer to respond to IFN lambda 1 over IFN-α. These events recapitulate the events that occur in vivo. This study constitutes the first use of a primary intestinal enteroid model to investigate the susceptibility of porcine enteroids to PEDV and to determine the antiviral response following infection. Our study provides important insights into the events associated with PEDV infection of the porcine intestine and provides a valuable in vitro model for studying not only PEDV but also other swine enteric viruses.",,"['Li, Liang', 'Fu, Fang', 'Guo, Shanshan', 'Wang, Hongfeng', 'He, Xijun', 'Xue, Mei', 'Yin, Lingdan', 'Feng, Li', 'Liu, Pinghuang']",,,,
,PMC,Individual and temporal variation in pathogen load predicts long-term impacts of an emerging infectious disease,http://dx.doi.org/10.1002/ecy.2613,PMC6415924,,,"Emerging infectious diseases increasingly threaten wildlife populations. Most studies focus on managing short-term epidemic properties, such as controlling early outbreaks. Predicting long-term endemic characteristics with limited retrospective data is more challenging. We used individual-based modelling informed by individual variation in pathogen load and transmissibility to predict long-term impacts of a lethal, transmissible cancer on Tasmanian devil (Sarcophilus harrisii) populations. For this, we employed Approximate Bayesian Computation to identify model scenarios that best matched known epidemiological and demographic system properties derived from ten years of data after disease emergence, enabling us to forecast future system dynamics. We show that the dramatic devil population declines observed thus far are likely attributable to transient dynamics (initial dynamics after disease emergence). Only 21% of matching scenarios led to devil extinction within 100 years following devil facial tumor disease (DFTD) introduction, whereas DFTD faded out in 57% of simulations. In the remaining 22% of simulations, disease and host coexisted for at least 100 years, usually with long-period oscillations. Our findings show that pathogen extirpation or host-pathogen coexistence are much more likely than the DFTD-induced devil extinction, with crucial management ramifications. Accounting for individual-level disease progression and the long-term outcome of devil-DFTD interactions at the population-level, our findings suggest that immediate management interventions are unlikely to be necessary to ensure the persistence of Tasmanian devil populations. This is because strong population declines of devils after disease emergence do not necessarily translate into long-term population declines at equilibria. Our modelling approach is widely applicable to other host-pathogen systems to predict disease impact beyond transient dynamics.",,"['Wells, Konstans', 'Hamede, Rodrigo K.', 'Jones, Menna E.', 'Hohenlohe, Paul A.', 'Storfer, Andrew', 'McCallum, Hamish I.']",,,,
,PMC,The Special Pathogens Research Network: Enabling Research Readiness,http://dx.doi.org/10.1089/hs.2018.0106,PMC6669031,,,"The 2013-2016 epidemic of Ebola virus disease (EVD) that originated in West Africa underscored many of the challenges to conducting clinical research during an ongoing infectious disease epidemic, both in the most affected countries of Guinea, Liberia, and Sierra Leone, as well as in the United States and Europe, where a total of 27 patients with EVD received care in biocontainment units. The Special Pathogens Research Network (SPRN) was established in the United States in November 2016 to provide an organizational structure to leverage the expertise of the 10 Regional Ebola and Other Special Pathogen Treatment Centers (RESPTCs); it was intended to develop and support infrastructure to improve readiness to conduct clinical research in the United States. The network enables the rapid activation and coordination of clinical research in the event of an epidemic and facilitates opportunities for multicenter research when the RESPTCs are actively caring for patients requiring a biocontainment unit. Here we provide an overview of opportunities identified in the clinical research infrastructure during the West Africa EVD epidemic and the SPRN activities to meet the ongoing challenges in the context of Ebola virus and other special pathogens.",,"['Kraft, Colleen S.', 'Kortepeter, Mark G.', 'Gordon, Bruce', 'Sauer, Lauren M.', 'Shenoy, Erica S.', 'Eiras, Daniel P.', 'Larson, LuAnn', 'Garland, Jennifer A.', 'Mehta, Aneesh K.', 'Barrett, Kevin', 'Price, Connie S.', 'Croyle, Caroline', 'West, Lauren R.', 'Noren, Brooke', 'Kline, Susan', 'Arguinchona, Christa', 'Arguinchona, Henry', 'Grein, Jonathan D.', 'Connally, Chad', 'McLellan, Susan', 'Risi, George F.', 'Uyeki, Timothy M.', 'Davey, Richard T.', 'Schweinle, Jo Ellen', 'Schwedhelm, Michelle M.', 'Harvey, Melissa', 'Hunt, Richard C.', 'Kratochvil, Christopher J.']",,,,
,PMC,Genomics and High-Consequence Infectious Diseases: A Scoping Review of Emerging Science and Potential Ethical Issues,http://dx.doi.org/10.1089/hs.2018.0108,PMC6424158,,,"Host genomic research on high-consequence infectious diseases is a growing area, but the ethical, legal, and social implications of such findings related to potential applications of the research have not yet been identified. While there is a robust ethical debate about the ethical, legal, and social implications of research during an emergency, there has been less consideration of issues facing research conducted outside of the scope of emergency response. Addressing the implications of research at an early stage (anticipatory ethics) helps define the issue space, facilitates preparedness, and promotes ethically and socially responsible practices. To lay the groundwork for more comprehensive anticipatory ethics work, this article provides a preliminary assessment of the state of the field with a scoping review of host genomic research on a subset of high-consequence infectious diseases of relevance to high-level isolation units, focusing on its ethically relevant features and identifying several ethical, legal, and social implications raised by the literature. We discuss the challenges of genomic studies of low-frequency, high-risk events and applications of the science, including identifying targets to guide the development of new therapeutics, improving vaccine development, finding biomarkers to predict disease outcome, and guiding decisions about repurposing existing drugs and genetic screening. Some ethical, legal, and social implications identified in the literature included the rise of systems biology and paradigm shifts in medical countermeasure development; controversies over repurposing of existing drugs; genetic privacy and discrimination; and benefit-sharing and global inequity as part of the broader ecosystem surrounding high-level isolation units. Future anticipatory ethics work should forecast the science and its applications; identify a more comprehensive list of ethical, legal, and social implications; and facilitate evaluation by multiple stakeholders to inform the integration of ethical concerns into high-level isolation unit policy and practice.",,"['Boyce, Angie M.', 'Garibaldi, Brian T.']",,,,
,PMC,Respiratory epithelial cells as master communicators during viral infections,http://dx.doi.org/10.1007/s40588-019-0111-8,PMC6779166,,,"PURPOSE OF REVIEW: Communication by epithelial cells during respiratory viral infections is critical in orchestrating effective anti-viral responses but also can lead to excessive inflammation. This review will evaluate studies that investigate how respiratory epithelial cells influence the behavior of immune cells and how epithelial cell/immune cell interactions contribute to antiviral responses and immunopathology outcomes. RECENT FINDINGS: Previous studies have characterized cytokine responses of virus-infected epithelial cells. More recent studies have carefully demonstrated the effects of these cytokines on cellular behaviors within the infected lung. Infected epithelial cells release exosomes that specifically regulate responses of monocytes and neighboring epithelial cells without promoting spread of virus. In contrast, rhinovirus-infected cells induce monocytes to upregulate expression of the viral receptor, promoting spread of the virus to alternate cell types. The precise alteration of PDL expression on infected epithelial cells has been shown to switch between inhibition and activation of antiviral responses. SUMMARY: These studies have more precisely defined the interactions between epithelial and immune cells during viral infections. This level of understanding is critical for the development of novel therapeutic strategies that promote effective antiviral responses or epithelial repair, or inhibit damaging inflammatory responses during severe respiratory viral infections.",,"Miura, Tanya A.",,,,
,PMC,Efficacy and Safety of Nitazoxanide in Addition to Standard of Care for the Treatment of Severe Acute Respiratory Illness,http://dx.doi.org/10.1093/cid/ciz100,PMC6853643,,,"BACKGROUND: Effective therapeutics for respiratory viruses are needed. Early data suggest that nitazoxanide (NTZ) may be beneficial for treating acute respiratory viral illness. METHODS: From March 2014 through March 2017, a double-blind, placebo-controlled trial was conducted in 260 participants ≥1 year old hospitalized with influenza-like illness at 6 hospitals in Mexico. Participants were randomized 1:1 to NTZ (age ≥12 years, 600 mg twice daily; age 4–11 years and 1–3 years, 200 or 100 mg twice daily, respectively) or placebo for 5 days in addition to standard of care. The primary endpoint was time from first dose to hospital discharge. Influenza reverse-transcription polymerase chain reaction and Respifinder 22 multiplex test were used for virus detection. RESULTS: Of 260 participants enrolled, 257 were randomized and took at least 1 dose of study treatment (intention-to-treat population): 130 in the NTZ group and 127 in the placebo group. The Kaplan-Meier estimate of the median duration of hospitalization was 6.5 (interquartile range [IQR], 4.0–9.0) days in the NTZ group vs 7.0 (IQR, 4.0–9.0) days in the placebo group (P = .56). Duration of hospitalization between the 2 treatments was similar in children (P = .29) and adults (P = .62), influenza A and B (P = .32), and other respiratory viruses. Seven (5.4%) and 6 (4.7%) participants in the NTZ and placebo groups, respectively, reported serious adverse events. CONCLUSIONS: Treatment with NTZ did not reduce the duration of hospital stay in severe influenza-like illness. Further analyses based on age and evaluations by virus did not reveal any subgroups that appeared to benefit from NTZ. CLINICAL TRIALS REGISTRATION: NCT02057757.",,"['Gamiño-Arroyo, Ana E', 'Guerrero, M Lourdes', 'McCarthy, Sean', 'Ramírez-Venegas, Alejandra', 'Llamosas-Gallardo, Beatriz', 'Galindo-Fraga, Arturo', 'Moreno-Espinosa, Sarbelio', 'Roldán-Aragón, Yuri', 'Araujo-Meléndez, Javier', 'Hunsberger, Sally', 'Ibarra-González, Violeta', 'Martínez-López, Julia', 'García-Andrade, Luis A', 'Kapushoc, Heather', 'Holley, H Preston', 'Smolskis, Mary C', 'Ruiz-Palacios, Guillermo M', 'Beigel, John H', None]",,,,
,PMC,Immune-Checkpoint Blockade Opposes CD8(+) T-cell Suppression in Human and Murine Cancer,http://dx.doi.org/10.1158/2326-6066.CIR-18-0054,PMC6476322,,,"Immune-checkpoint blockade enhances antitumor responses against cancers. One cancer type that is sensitive to checkpoint blockade is squamous cell carcinoma of the head and neck (SCCHN), which we use here to study limitations of this treatment modality. We observed that CD8(+) tumor infiltrating lymphocytes (TIL) in SCCHN and melanoma express excess immune checkpoints components PD-1 and Tim-3 and are also CD27(−)/CD28(−), a phenotype we previously associated with immune dysfunction and suppression. In ex vivo experiments, patients’ CD8(+) TILs with this phenotype suppressed proliferation of autologous peripheral blood T cells. Similar phenotype and function of TILs was observed in the TC-1 mouse tumor model. Treatment of TC-1 tumors with anti-PD-1 or anti-Tim-3 slowed tumor growth in vivo and reversed the suppressive function of multi-checkpoint(+) CD8(+) TIL. Similarly, treatment of both human and mouse PD-1(+) Tim-3(+) CD8(+) TILs with anti-checkpoint antibodies ex vivo reversed their suppressive function. These suppressive CD8(+) TILs from mice and humans expressed ligands for PD-1 and Tim-3 and exerted their suppressive function via IL10 and close contact. To model therapeutic strategies, we combined anti-PD-1 blockade with IL7 cytokine therapy or with transfer of antigen specific T cells. Both strategies resulted in synergistic antitumor effects and reduced suppressor cell function. These findings enhance our understanding of checkpoint blockade in cancer treatment and identify strategies to promote synergistic activities in the context of other immunotherapies.",,"['Pfannenstiel, Lukas W.', 'Diaz-Montero, C. Marcela', 'Tian, Ye F.', 'Scharpf, Joseph', 'Ko, Jennifer S.', 'Gastman, Brian R.']",,,,
,PMC,P-Mart: Interactive Analysis of Ion Abundance Global Proteomics Data,http://dx.doi.org/10.1021/acs.jproteome.8b00840,PMC7032029,,,"The use of mass-spectrometry-based techniques for global protein profiling of biomedical or environmental experiments has become a major focus in research centered on biomarker discovery; however, one of the most important issues recently highlighted in the new era of omics data generation is the ability to perform analyses in a robust and reproducible manner. This has been hypothesized to be one of the issues hindering the ability of clinical proteomics to successfully identify clinical diagnostic and prognostic biomarkers of disease. P-Mart (https://pmart.labworks.org) is a new interactive web-based software environment that enables domain scientists to perform quality-control processing, statistics, and exploration of large-complex proteomics data sets without requiring statistical programming. P-Mart is developed in a manner that allows researchers to perform analyses via a series of modules, explore the results using interactive visualization, and finalize the analyses with a collection of output files documenting all stages of the analysis and a report to allow reproduction of the analysis.",,"['Bramer, Lisa M.', 'Stratton, Kelly G.', 'White, Amanda M.', 'Bleeker, Ameila H.', 'Kobold, Markus A.', 'Waters, Katrina M.', 'Metz, Thomas O.', 'Rodland, Karin D.', 'Webb-Robertson, Bobbie-Jo M.']",,,,
,PMC,Existing Host Range Mutations Constrain Further Emergence of RNA Viruses,http://dx.doi.org/10.1128/JVI.01385-18,PMC6364021,,,"RNA viruses are capable of rapid host shifting, typically due to a point mutation that confers expanded host range. As additional point mutations are necessary for further expansions, epistasis among host range mutations can potentially affect the mutational neighborhood and frequency of niche expansion. We mapped the mutational neighborhood of host range expansion using three genotypes of the double-stranded RNA (dsRNA) bacteriophage φ6 (wild type and two isogenic host range mutants) on the novel host Pseudomonas syringae pv. atrofaciens. Both Sanger sequencing of 50 P. syringae pv. atrofaciens mutant clones for each genotype and population Illumina sequencing revealed the same high-frequency mutations allowing infection of P. syringae pv. atrofaciens. Wild-type φ6 had at least nine different ways of mutating to enter the novel host, eight of which are in p3 (host attachment protein gene), and 13/50 clones had unchanged p3 genes. However, the two isogenic mutants had dramatically restricted neighborhoods: only one or two mutations, all in p3. Deep sequencing revealed that wild-type clones without mutations in p3 likely had changes in p12 (morphogenic protein), a region that was not polymorphic for the two isogenic host range mutants. Sanger sequencing confirmed that 10/13 of the wild-type φ6 clones had nonsynonymous mutations in p12, and 2 others had point mutations in p9 and p5. None of these genes had previously been associated with host range expansion in φ6. We demonstrate, for the first time, epistatic constraint in an RNA virus due to host range mutations themselves, which has implications for models of serial host range expansion. IMPORTANCE RNA viruses mutate rapidly and frequently expand their host ranges to infect novel hosts, leading to serial host shifts. Using an RNA bacteriophage model system (Pseudomonas phage φ6), we studied the impact of preexisting host range mutations on another host range expansion. Results from both clonal Sanger and Illumina sequencing show that extant host range mutations dramatically narrow the neighborhood of potential host range mutations compared to that of wild-type φ6. This research suggests that serial host-shifting viruses may follow a small number of molecular paths to enter additional novel hosts. We also identified new genes involved in φ6 host range expansion, expanding our knowledge of this important model system in experimental evolution.",,"['Zhao, Lele', 'Seth-Pasricha, Mansha', 'Stemate, Dragoş', 'Crespo-Bellido, Alvin', 'Gagnon, Jacqueline', 'Draghi, Jeremy', 'Duffy, Siobain']",,,,
,PMC,Efficient Inhibition of Avian and Seasonal Influenza A Viruses by a Virus-Specific Dicer-Substrate Small Interfering RNA Swarm in Human Monocyte-Derived Macrophages and Dendritic Cells,http://dx.doi.org/10.1128/JVI.01916-18,PMC6364019,,,"Influenza A viruses (IAVs) are viral pathogens that cause epidemics and occasional pandemics of significant mortality. The generation of efficacious vaccines and antiviral drugs remains a challenge due to the rapid appearance of new influenza virus types and antigenic variants. Consequently, novel strategies for the prevention and treatment of IAV infections are needed, given the limitations of the presently available antivirals. Here, we used enzymatically produced IAV-specific double-stranded RNA (dsRNA) molecules and Giardia intestinalis Dicer for the generation of a swarm of small interfering RNA (siRNA) molecules. The siRNAs target multiple conserved genomic regions of the IAVs. In mammalian cells, the produced 25- to 27-nucleotide-long siRNA molecules are processed by endogenous Dicer into 21-nucleotide siRNAs and are thus designated Dicer-substrate siRNAs (DsiRNAs). We evaluated the efficacy of the above DsiRNA swarm at preventing IAV infections in human primary monocyte-derived macrophages and dendritic cells. The replication of different IAV strains, including avian influenza H5N1 and H7N9 viruses, was significantly inhibited by pretransfection of the cells with the IAV-specific DsiRNA swarm. Up to 7 orders of magnitude inhibition of viral RNA expression was observed, which led to a dramatic inhibition of IAV protein synthesis and virus production. The IAV-specific DsiRNA swarm inhibited virus replication directly through the RNA interference pathway although a weak induction of innate interferon responses was detected. Our results provide direct evidence for the feasibility of the siRNA strategy and the potency of DsiRNA swarms in the prevention and treatment of influenza, including the highly pathogenic avian influenza viruses. IMPORTANCE In spite of the enormous amount of research, influenza virus is still one of the major challenges for medical virology due to its capacity to generate new variants, which potentially lead to severe epidemics and pandemics. We demonstrated here that a swarm of small interfering RNA (siRNA) molecules, including more than 100 different antiviral RNA molecules targeting the most conserved regions of the influenza A virus genome, could efficiently inhibit the replication of all tested avian and seasonal influenza A variants in human primary monocyte-derived macrophages and dendritic cells. The wide antiviral spectrum makes the virus-specific siRNA swarm a potentially efficient treatment modality against both avian and seasonal influenza viruses.",,"['Jiang, Miao', 'Österlund, Pamela', 'Westenius, Veera', 'Guo, Deyin', 'Poranen, Minna M.', 'Bamford, Dennis H.', 'Julkunen, Ilkka']",,,,
,PMC,The Dengue Virus Nonstructural Protein 1 (NS1) Is Secreted from Mosquito Cells in Association with the Intracellular Cholesterol Transporter Chaperone Caveolin Complex,http://dx.doi.org/10.1128/JVI.01985-18,PMC6364000,,,"Dengue virus (DENV) is a mosquito-borne virus of the family Flaviviridae. The RNA viral genome encodes three structural and seven nonstructural proteins. Nonstructural protein 1 (NS1) is a multifunctional protein actively secreted in vertebrate and mosquito cells during infection. In mosquito cells, NS1 is secreted in a caveolin-1-dependent manner by an unconventional route. The caveolin chaperone complex (CCC) is a cytoplasmic complex formed by caveolin-1 and the chaperones FKBP52, Cy40, and CyA and is responsible for the cholesterol traffic inside the cell. In this work, we demonstrate that in mosquito cells, but not in vertebrate cells, NS1 associates with and relies on the CCC for secretion. Treatment of mosquito cells with classic secretion inhibitors, such as brefeldin A, Golgicide A, and Fli-06, showed no effect on NS1 secretion but significant reductions in recombinant luciferase secretion and virion release. Silencing the expression of CAV-1 or FKBP52 with short interfering RNAs or the inhibition of CyA by cyclosporine resulted in significant decrease in NS1 secretion, again without affecting virion release. Colocalization, coimmunoprecipitation, and proximity ligation assays indicated that NS1 colocalizes and interacts with all proteins of the CCC. In addition, CAV-1 and FKBP52 expression was found augmented in DENV-infected cells. Results obtained with Zika virus-infected cells suggest that in mosquito cells, ZIKV NS1 follows the same secretory pathway as that observed for DENV NS1. These results uncover important differences in the dengue virus-cell interactions between the vertebrate host and the mosquito vector as well as novel functions for the chaperone caveolin complex. IMPORTANCE The dengue virus protein NS1 is secreted efficiently from both infected vertebrate and mosquito cells. Previously, our group reported that NS1 secretion in mosquito cells follows an unconventional secretion pathway dependent on caveolin-1. In this work, we demonstrate that in mosquito cells, but not in vertebrate cells, NS1 secretion takes place in association with the chaperone caveolin complex, a complex formed by caveolin-1 and the chaperones FKBP52, CyA, and Cy40, which are in charge of cholesterol transport inside the cell. Results obtained with ZIKV-infected mosquito cells suggest that ZIKV NS1 is released following an unconventional secretory route in association with the chaperone caveolin complex. These results uncover important differences in the virus-cell interactions between the vertebrate host and the mosquito vector, as well as novel functions for the chaperone caveolin complex. Moreover, manipulation of the NS1 secretory route may prove a valuable strategy to combat these two mosquito-borne diseases.",,"['Rosales Ramirez, Romel', 'Ludert, Juan E.']",,,,
,PMC,Autophagy Promotes Replication of Influenza A Virus In Vitro,http://dx.doi.org/10.1128/JVI.01984-18,PMC6363991,,,"Influenza A virus (IAV) infection could induce autophagosome accumulation. However, the impact of the autophagy machinery on IAV infection remains controversial. Here, we showed that induction of cellular autophagy by starvation or rapamycin treatment increases progeny virus production, while disruption of autophagy using a small interfering RNA (siRNA) and pharmacological inhibitor reduces progeny virus production. Further studies revealed that alteration of autophagy significantly affects the early stages of the virus life cycle or viral RNA synthesis. Importantly, we demonstrated that overexpression of both the IAV M2 and NP proteins alone leads to the lipidation of LC3 to LC3-II and a redistribution of LC3 from the cytosol to punctate vesicles indicative of authentic autophagosomes. Intriguingly, both M2 and NP colocalize and interact with LC3 puncta during M2 or NP transfection alone and IAV infection, leading to an increase in viral ribonucleoprotein (vRNP) export and infectious viral particle formation, which indicates that the IAV-host autophagy interaction plays a critical role in regulating IAV replication. We showed that NP and M2 induce the AKT-mTOR-dependent autophagy pathway and an increase in HSP90AA1 expression. Finally, our studies provided evidence that IAV replication needs an autophagy pathway to enhance viral RNA synthesis via the interaction of PB2 and HSP90AA1 by modulating HSP90AA1 expression and the AKT-mTOR signaling pathway in host cells. Collectively, our studies uncover a new mechanism that NP- and M2-mediated autophagy functions in different stages of virus replication in the pathogenicity of influenza A virus. IMPORTANCE Autophagy impacts the replication cycle of many viruses. However, the role of the autophagy machinery in IAV replication remains unclear. Therefore, we explored the detailed mechanisms utilized by IAV to promote its replication. We demonstrated that IAV NP- and M2-mediated autophagy promotes IAV replication by regulating the AKT-mTOR signaling pathway and HSP90AA1 expression. The interaction of PB2 and HSP90AA1 results in the increase of viral RNA synthesis first; subsequently the binding of NP to LC3 favors vRNP export, and later the interaction of M2 and LC3 leads to an increase in the production of infectious viral particles, thus accelerating viral progeny production. These findings improve our understanding of IAV pathogenicity in host cells.",,"['Wang, Ruifang', 'Zhu, Yinxing', 'Zhao, Jiachang', 'Ren, Chenwei', 'Li, Peng', 'Chen, Huanchun', 'Jin, Meilin', 'Zhou, Hongbo']",,,,
,PMC,History and Future of Nucleic Acid Amplification Technology Blood Donor Testing,http://dx.doi.org/10.1159/000496749,PMC6514489,,,"The introduction of blood donor screening by virus nucleic acid amplification technology (NAT) in the mid to late 1990s was driven by the so-called AIDS and hepatitis C virus (HCV) epidemic, with thousands of recipients of infected blood products and components. Plasma fractionators were the first to introduce NAT testing besides pathogen reduction procedures, to reduce the virus transmission risk through their products. To achieve a similar safety standard, NAT was then also introduced for labile blood components. German transfusion centres were the first to start in-house NAT testing of their donations in pools of up to 96 samples for HCV, hepatitis B virus (HBV), and human immunodeficiency virus-1 (HIV-1). Years later the diagnostics industry provided commercial HCV and HIV-1 and later HBV NAT tests on automated platforms. NAT tests for HIV-2, hepatitis A virus, and Parvovirus B19 followed, again driven by transfusion centres with their in-house tests. When severe acute respiratory syndrome corona virus (SARS-CoV) and West Nile Virus emerged it was the NAT that enabled the manufacturers and transfusion centres to instantly introduce sensitive and specific screening tests. Subsequent automation including sample preparation has significantly reduced the costs and complexity of the procedure and made it affordable to middle income countries as well. Currently more than 60 million donations per year are NAT tested worldwide and the remaining residual risk of virus transmission by blood components and products could be reduced to almost zero. Automation rendered possible the reduction of pool size in conjunction with increased throughput and sensitivity. Thus, antibody and antigen testing may be dispensable in the long run, particularly in the combination of NAT testing with pathogen reduction. There are new technologies on the horizon like digital droplet PCR, next-generation sequencing, lab-on-a-chip, and digital antigen assays, which are comparably sensitive. However, each of these has limitations, either in throughput, costs, automation, time to result, specificity, or the need for NAT as an integral part of the technology. Thus, NAT is still the shortest and most efficient means to the result. Donor screening NAT also contributed significantly to our knowledge on how fast viruses replicate, and on the respective diagnostic window. In conjunction with animal and patient studies, we have learned more about the minimal infectious dose and the epidemics in the donor population.",,"Roth, Willi Kurt",,,,
,PMC,What is the evidence that bovine coronavirus is a biologically significant respiratory pathogen in cattle?,,PMC6340311,,,"Coronaviruses, including bovine coronavirus (BCoV), are etiologically associated with enteric and respiratory disease across a wide range of mammalian and avian species. The role of BCoV in calfhood diarrhea is well-established, but its role in the bovine respiratory disease complex (BRDC) has been controversial. This review re-examines the evidence that BCoV is a significant pathogen in the BRDC.",,"Ellis, John",,,,
,PMC,Bilateral phacoemulsification and intraocular lens implantation in a young African lion (Panthera leo),,PMC6340255,,,"An 18-month-old intact female lioness (Panthera leo) was referred to the Clinica Veterinaria Roma Sud for evaluation of bilateral cataracts. Phacoemulsification and implantation of +30 diopter intraocular lens (IOL) were performed bilaterally. Seven years after surgery, the IOL remained centrally positioned and the patient had normal activity.",,"['Viñas, Marta', 'D’Anna, Nunzio', 'Guandalini, Adolfo', 'Capasso, Michele', 'Nocerino, Maurizio', 'Guerriero, Alessandra', 'Sapienza, John']",,,,
,PMC,Feline infectious peritonitis in a cat presented because of papular skin lesions,,PMC6340254,,,"A 19-week-old neutered male domestic shorthair cat was examined because of multiple raised pruritic skin lesions along the dorsal head and back. Histopathology of biopsies of the lesions detected nodular pyogranulomatous dermatitis with vasculitis and necrosis, leading to a suspicion of feline infectious peritonitis (FIP). Postmortem examination revealed gross lesions consistent with FIP. Histopathologic lesions and positive immunohistochemical staining for feline coronavirus in multiple tissues, including the skin, confirmed the diagnosis of FIP. The current case was similar to previous cases, except for the initial presentation with cutaneous lesions and no other clinical signs, which had not been reported previously.",,"['Redford, Tony', 'Al-Dissi, Ahmad N.']",,,,
,PMC,Nipah virus disease: A rare and intractable disease,http://dx.doi.org/10.5582/irdr.2018.01130,PMC6409114,,,"Nipah virus, an enveloped ribonucleic acid virus, has been a major cause of encephalitis out-breaks with high mortality, primarily in the Indo-Bangladesh regions. Except for the first outbreak in Malaysia-Singapore, which was related to contact with pigs and the outbreak in Philippines associated with horse slaughter, most other outbreaks have affected the Indo- Bangladesh regions. The Indo-Bangladesh outbreaks were associated with consumption of raw date palm sap contaminated by fruit bats and had a very high secondary attack rate. The patient usually presents with fever, encephalitis and/or respiratory involvement with or without thrombocytopenia, leukopenia and transaminitis. Diagnosis can be confirmed by isolation and nucleic acid amplification in the acute phase or antibody detection during the convalescent phase. Treatment is mostly limited to supportive care and syndromic management of acute encephalitis syndrome. Ribavirin, m102.4 monoclonal antibody and favipiravir are the only anti-virals with some activity against Nipah virus. Standard precautions, hand hygiene and personal protective equipments are the cornerstone of comprehensive infection prevention and control strategy. With the recent outbreaks affecting newer geographical areas, there is a need for physicians to be aware of this disease and keep abreast of its current detection and management strategies.",,"['Banerjee, Sayantan', 'Gupta, Nitin', 'Kodan, Parul', 'Mittal, Ankit', 'Ray, Yogiraj', 'Nischal, Neeraj', 'Soneja, Manish', 'Biswas, Ashutosh', 'Wig, Naveet']",,,,
,PMC,Dual-degree MBBS-MPH programs in Saudi Arabia: A call for implementation,http://dx.doi.org/10.4103/jfmpc.jfmpc_461_18,PMC6436275,30984637,CC BY-NC-SA,"Nowadays, any healthcare problem should be dealt with in a multidisciplinary approach that employs not only treating the symptoms of the problem but also its source. This simply implies the necessity to produce well-rounded medical graduates (physicians) who can competently integrate clinical knowledge/skills (for disease treatment) and public health knowledge/skills (for disease prevention). Moreover, the medical training (MD/MBBS curriculum) largely gives emphasis to the clinical skills needed to treat individual patients, whereas public health training (MPH degree) emphasizes the methods needed to improve the overall community health. Bridging the gap between patients and community is best achieved through a combined multidisciplinary training in both medicine and public health, that is, dual-degree MBBS-MPH programs are the way forward. In United States, for example, there are >80 medical schools that offer such joint MD-MPH programs, whereas there is none in Saudi Arabia. Herein, I call on higher education bodies to implement dual-degree MBBS-MPH programs in Saudi Arabia. To the best of knowledge, this is the first ever report to call for such an innovative implementation. Also, this short communication briefly sheds light on background, rationale, benefits, curriculum design, and future directions of such programs. The implications of this perspective (i.e. dual-degree MBBS-MPH programs) should not be limited to Saudi Arabia only; rather, it should be contemplated by the other medical curricula in the different countries.",2019 Feb,"['Abu-Zaid, Ahmed', 'Eshaq, Abdulaziz M.', 'Alkattan, Khaled']",J Family Med Prim Care,,,
,PMC,Knowledge and practices of primary health care physicians regarding updated guidelines of MERS-CoV infection in Abha city,http://dx.doi.org/10.4103/jfmpc.jfmpc_336_18,PMC6436268,30984654,CC BY-NC-SA,"BACKGROUND: Human coronaviruses (hCoV) usually cause mild to moderate upper respiratory tract illnesses. The novel coronavirus (nCoV), or Middle East respiratory syndrome coronavirus (MERS-CoV), is a particular strain different from any other known hCoV with the possibility of human and also zoonotic transmissions. The aim of the study to assess primary health care (PHC) physicians’ knowledge and adherence regarding Saudi Ministry of Health guidelines regarding MERS-CoV. MATERIALS AND METHODS: A cross-sectional study design was followed to include 85 PHC physicians in Abha city. An interview questionnaire has been designed by the researcher that was used to assess knowledge and practices of PHC physicians regarding diagnosis and management of MERS-CoV. It includes personal characteristics, the MERS-CoV knowledge assessment questionnaire, and practices related to adherence toward guidelines regarding MERS-CoV. RESULTS: PHC physicians’ knowledge gaps regarding MERS-CoV included protected exposure (32.9%), highest seasonal incidence of MERS-CoV in Saudi Arabia (60%), relation between incidence of MERS-CoV and overcrowding (62.4%), case fatality of MERS-CoV cases (63.5%), and collecting specimens from MERS-CoV patients (64.7%). The knowledge of PHC physicians about MERS-CoV was poor among 5.9%, good among 63.5%, and excellent among 30.6%. Personal protective equipment to be used when seeing suspected cases of MERS-CoV infection were mainly the mask (94.1%), gloves (78.8%), the gown (60%), goggles (31.8%), and the cap (22.4%). All participants stated that the most important standard precaution that should be applied when seeing a case of MERS-CoV infection is hand washing, whereas 97.6% stated that the most important respiratory precaution to prevent transmission of respiratory infections in PHC setting when seeing a case of MERS-CoV infection is masking and separation of suspected MERS-CoV patients, and 81.2% stated that upon exit from the room of a MERS-CoV patient, the physician should remove and discard personal protective equipment. PHC physicians’ knowledge about MERS-CoV differed significantly according to their nationality (P = 0.038), with non-Saudi physicians expressing higher percent of excellent knowledge than Saudi physicians (40% and 20%, respectively). Those who attended continuing medical education (CME) activities had significantly higher percent of excellent knowledge than those who did not attend a CME activity (55.6% and 23.9%, respectively, P = 0.011). PHC physicians’ knowledge did not differ significantly according to their age, gender, qualification, experience in PHC, and practice-related adherence to guidelines. PHC physicians’ practice-related adherence to guidelines about MERS-CoV differed significantly according to their position (P = 0.035), with specialists having the highest percent of excellent practice (13%). CONCLUSIONS: There are knowledge gaps among PHC physicians in Abha city, and their practice is suboptimal regarding MERS-CoV infection. Less than one-fourth of PHC physicians attend CME activities about MERS-CoV infection. However, significantly less practice-related adherence to guidelines are associated with Saudi PHC physicians, those who did not attend a related CME activity, and MBBS qualified physicians’ general practitioners. To increase awareness, more CME activities related to MERS-CoV infection management needs to be organized.",2019 Feb,"['Al-Amri, Saad', 'Bharti, Rishi', 'Alsaleem, Safar A.', 'Al-Musa, Hassan M.', 'Chaudhary, Shweta', 'Al-Shaikh, Ayub A.']",J Family Med Prim Care,,,
,PMC,Approaches for investigating the extracellular signaling function of ISG15,http://dx.doi.org/10.1016/bs.mie.2018.12.027,PMC6472260,,,"ISG15 is a ubiquitin-like protein (Ubl) that is expressed in response to Type 1 Interferon (IFN-α/β) signaling. Remarkably, ISG15 has three distinct biochemical activities involved in innate immune responses to viral and/or microbial infections. The canonical function of ISG15 is as a posttranslational modifier, and protein ISGylation has been demonstrated to be antiviral. A second intracellular function, independent of conjugation activity, is attenuation of IFN-α/β signaling at the interferon receptor, which appears to be important for terminating IFN responses. The third function of ISG15, and the focus of this chapter, is as an extracellular signaling molecule that promotes the secretion of Type 2 Interferon (IFN-γ) by Natural Killer (NK) cells. This function is important for control of microbial infections, including mycobacterial infections. Here, we describe methods for purification of ISG15, preparation, and culture of primary peripheral blood mononuclear cells (PBMCs) and NK-92 cells, assays for IL-12- and ISG15-dependent cytokine (IFN-γ and IL-10) secretion, and assays for initial intracellular signaling events triggered by extracellular ISG15.",,"['Swaim, Caleb D.', 'Canadeo, Larissa A.', 'Huibregtse, Jon M.']",,,,
,PMC,Retinal Findings in Young Children With Increased Intracranial Pressure From Nontraumatic Causes,http://dx.doi.org/10.1542/peds.2018-1182,PMC6361344,,,"OBJECTIVES: Increased intracranial pressure (ICP) has been suggested in legal settings as an alternative cause of retinal hemorrhages (RHs) in young children who may have sustained abusive head trauma. We assessed the prevalence and characteristics of RHs in children with increased ICP. METHODS: We conducted a prospective, multicenter study of children <4 years old with newly diagnosed increased ICP as determined by using direct measurement and/or clinical criteria. Infants who were premature, neonates, and suspected survivors of abusive head trauma were excluded on the basis of nonocular findings. Fundus examinations were performed; extent, number, and type of RH in each of 4 distinct retinal zones were recorded. RESULTS: Fifty-six children (27 boys) were studied (mean age 15.4 months; range 1–43 months). All of the children had elevated ICP that required intervention. One child had papilledema. No child (0%; 95% confidence interval: 0%–6.4%) or eye (0%; 95% confidence interval: 0%–3.3%) was found to have an RH. Causes of increased ICP included hydrocephalus, intraventricular hemorrhage, congenital malformations, malfunctioning shunts, and the presence of intracranial space-occupying lesions. CONCLUSIONS: Although acute increased ICP can present in children with a pattern of peripapillary superficial RHs in the presence of papilledema, our study supports the conclusion that RHs rarely occur in the absence of optic disc swelling and do not present beyond the peripapillary area in the entities we have studied.",,"['Shi, Angell', 'Kulkarni, Abhaya', 'Feldman, Kenneth W.', 'Weiss, Avery', 'McCourt, Emily A.', 'Schloff, Susan', 'Partington, Michael', 'Forbes, Brian', 'Geddie, Brooke E.', 'Bierbrauer, Karin', 'Phillips, Paul H.', 'Rogers, David L.', 'Abed Alnabi, Waleed', 'Binenbaum, Gil', 'Levin, Alex V.']",,,,
,PMC,Unexpected receptor functional mimicry elucidates activation of coronavirus fusion,http://dx.doi.org/10.1016/j.cell.2018.12.028,PMC6751136,,,"Recent outbreaks of severe acute respiratory syndrome and Middle-East respiratory syndrome along with the threat of a future coronavirus-mediated pandemic underscore the importance of finding ways to combat these viruses. The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies. To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors. Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry. These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.",,"['Walls, Alexandra C.', 'Xiong, Xiaoli', 'Park, Young-Jun', 'Tortorici, M. Alejandra', 'Snijder, Joost', 'Quispe, Joel', 'Cameroni, Elisabetta', 'Gopal, Robin', 'Dai, Mian', 'Lanzavecchia, Antonio', 'Zambon, Maria', 'Rey, Félix A.', 'Corti, Davide', 'Veesler, David']",,,,
,PMC,Fundamental Concepts for Semiquantitative Tissue Scoring in Translational Research,http://dx.doi.org/10.1093/ilar/ily025,PMC6927897,,,"Failure to reproduce results from some scientific studies has raised awareness of the critical need for reproducibility in translational studies. Macroscopic and microscopic examination is a common approach to determine changes in tissues, but text descriptions and visual images have limitations for group comparisons. Semiquantitative scoring is a way of transforming qualitative tissue data into numerical data that allow more robust group comparisons. Semiquantitative scoring has broad uses in preclinical and clinical studies for evaluation of tissue lesions. Reproducibility can be improved by constraining bias through appropriate experimental design, randomization of tissues, effective use of multidisciplinary collaborations, and valid masking procedures. Scoring can be applied to tissue lesions (eg, size, distribution, characteristics) and also to tissues through evaluation of staining distribution and intensity. Semiquantitative scores should be validated to demonstrate relevance to biological data and to demonstrate observer reproducibility. Statistical analysis should make use of appropriate tests to give robust confidence in the results and interpretations. Following key principles of semiquantitative scoring will not only enhance descriptive tissue evaluation but also improve quality, reproducibility, and rigor of tissue studies.",,"['Meyerholz, David K', 'Beck, Amanda P']",,,,
,PMC,Molecular cloning and transcriptional regulation of Indian peafowl (Pavo cristatus) IFN-α gene,http://dx.doi.org/10.1007/s12192-018-00962-0,PMC6439081,,,"Interferon-α (IFN-α) resists viral infections by triggering the transcription of a diverse range of antiviral IFN-stimulated genes (ISGs). However, information about the Indian peafowl (Pavo cristatus) IFN-α (PcIFN-α) has not been reported. In this study, a PcIFN-α gene was amplified, which encoded a protein of 193 amino acids with a 26-amino acid signal peptide sharing 72.16–95.70% identity with other avians in Aves. After expression in prokaryote, PcIFN-α was analyzed for its physicochemical property and antiviral activity. Intriguingly, compared with chicken IFN-α, an effective viral infection therapeutic agent, PcIFN-α showed superior anti-VSV, NDV, and AIV activities, which were then abrogated by rabbit anti-PcIFN-α antibodies in vitro. Moreover, PcIFN-α was shown to be highly sensitive to trypsin; however, it remained stable despite changes in pH and temperature. Additionally, PcIFN-α induced the transcriptional or translational levels of Mx1 and ISG12 genes time-dependently. Overall, the present study revealed that PcIFN-α is a potential novel effective therapeutic agent in antiviral defense responses in peafowl, improving understanding of its involvement in bird antiviral defense.",,"['Wang, Yu', 'Zhao, Hongjing', 'Liu, Juanjuan', 'Shao, Yizhi', 'Xing, Mingwei']",,,,
,PMC,Multicenter Clinical Evaluation of the Automated Aries Bordetella Assay,http://dx.doi.org/10.1128/JCM.01471-18,PMC6355524,,,"Molecular methods offer superior sensitivity and specificity and reduce testing turnaround time from days to hours for detection of Bordetella pertussis and Bordetella parapertussis. In this study, we evaluated the performance of the automated PCR-based Aries Bordetella Assay, which detects both B. pertussis and B. parapertussis directly from nasopharyngeal swab specimens. The limits of detection (LoDs) were 1,800 CFU·ml(−1) for B. pertussis and 213 CFU·ml(−1) for B. parapertussis. The assay detected 16/18 unique B. pertussis/B. parapertussis strains. Of 71 potentially cross-reacting organisms, 5 generated false positives in 1/6 replicates; none of 6 additional Bordetella spp. were erroneously detected. Specimens were stable at 20 to 25°C for at least 10 h, at 4 to 8°C for 10 days, and at temperatures not exceeding −70°C for 6 months. Of 1,052 nasopharyngeal specimens from patients with suspected pertussis, 3.0% (n = 32) were B. pertussis positive and 0.2% (n = 2) were B. parapertussis positive. Combining these data with Aries Bordetella Assay data from 57 nasopharyngeal samples with previously confirmed B. pertussis or B. parapertussis data and with data from 50 contrived B. parapertussis samples, the proportions of positive and negative agreement of the respective Aries assays with the reference assays were 97.1% and 99.0% for B. pertussis and 100% and 99.7% for B. parapertussis. The Aries Bordetella Assay provides accurate detection and distinction of B. pertussis and B. parapertussis infections within 2 h. (This study has been registered at ClinicalTrials.gov under registration no. NCT02862262.)",,"['Relich, Ryan F.', 'Leber, Amy', 'Young, Stephen', 'Schutzbank, Ted', 'Dunn, Ronald', 'Farhang, Janet', 'Uphoff, Timothy S.']",,,,
,PMC,Immunocytochemistry of mesenteric lymph node fine-needle aspirates in the diagnosis of feline infectious peritonitis,http://dx.doi.org/10.1177/1040638718825280,PMC6838827,,,"Immunohistochemistry (IHC) of tissue samples is considered the gold standard for diagnosing feline infectious peritonitis (FIP), and, in cats without body cavity effusion, IHC is the only method available to establish definitive antemortem diagnosis. However, IHC requires invasive tissue sample collection. We evaluated sensitivity and specificity of an immunocytochemical assay of fine-needle aspirates (FNAs) of mesenteric lymph nodes that can be obtained noninvasively by ultrasound-guided aspiration to diagnose FIP. FNAs of mesenteric lymph nodes were obtained postmortem from 41 cats suspected of having FIP based on clinical and/or laboratory findings. FIP was confirmed immunohistochemically in 30 cats. In the other 11 cats, a disease other than FIP, which explained the clinical signs, was diagnosed histopathologically. Immunocytochemistry (ICC) was performed as an avidin–biotin complex method using a monoclonal anti-FCoV IgG 2A. Sensitivity, specificity, negative and positive predictive values (NPV, PPV, respectively) including 95% confidence intervals (95% CIs) were determined. ICC was positive in 17 of 30 cats with FIP, but also in 1 of 11 control cats that was diagnosed with lymphoma. Sensitivity of ICC was 53% (95% CI: 34–72); specificity 91% (95% CI: 59–100); NPV 42% (95% CI: 22–63); and PPV 94% (95% CI: 71–100). In a lethal disease such as FIP, specificity is most important in order to avoid euthanasia of unaffected cats. Given that a false-positive result occurred and FIP was correctly detected in only approximately half of the cases of FIP, ICC of mesenteric lymph node FNA alone cannot reliably confirm or exclude FIP, but can be a helpful test in conjunction with other diagnostic measures.",,"['Felten, Sandra', 'Hartmann, Katrin', 'Doerfelt, Stefanie', 'Sangl, Laura', 'Hirschberger, Johannes', 'Matiasek, Kaspar']",,,,
,PMC,Structure-Based Vaccine Antigen Design,http://dx.doi.org/10.1146/annurev-med-121217-094234,PMC6936610,,,"Enabled by new approaches for rapid identification and selection of human monoclonal antibodies, atomic-level structural information for viral surface proteins, and capacity for precision engineering of protein immunogens and self-assembling nanoparticles, a new era of antigen design and display options has evolved. While HIV-1 vaccine development has been a driving force behind these technologies and concepts, clinical proof-of-concept for structure-based vaccine design may first be achieved for respiratory syncytial virus (RSV), where conformation-dependent access to neutralization-sensitive epitopes on the fusion glycoprotein determines the capacity to induce potent neutralizing activity. Success with RSV has motivated structure-based stabilization of other class I viral fusion proteins for use as immunogens and demonstrated the importance of structural information for developing vaccines against other viral pathogens particularly difficult targets that have resisted prior vaccine development efforts. Solving viral surface structures also supports rapid vaccine antigen design and application of platform manufacturing approaches for emerging pathogens.",,"['Graham, Barney S.', 'Gilman, Morgan S. A.', 'McLellan, Jason S.']",,,,
,PMC,Excess Deaths Attributable to Influenza-Like Illness in the ESRD Population,http://dx.doi.org/10.1681/ASN.2018060581,PMC6362626,,,"BACKGROUND: Morbidity and mortality vary seasonally. Timing and severity of influenza seasons contribute to those patterns, especially among vulnerable populations such as patients with ESRD. However, the extent to which influenza-like illness (ILI), a syndrome comprising a range of potentially serious respiratory tract infections, contributes to mortality in patients with ESRD has not been quantified. METHODS: We used data from the Centers for Disease Control and Prevention (CDC) Outpatient Influenza-like Illness Surveillance Network and Centers for Medicare and Medicaid Services ESRD death data from 2000 to 2013. After addressing the increasing trend in deaths due to the growing prevalent ESRD population, we calculated quarterly relative mortality compared with average third-quarter (summer) death counts. We used linear regression models to assess the relationship between ILI data and mortality, separately for quarters 4 and 1 for each influenza season, and model parameter estimates to predict seasonal mortality counts and calculate excess ILI-associated deaths. RESULTS: An estimated 1% absolute increase in quarterly ILI was associated with a 1.5% increase in relative mortality for quarter 4 and a 2.0% increase for quarter 1. The average number of annual deaths potentially attributable to ILI was substantial, about 1100 deaths per year. CONCLUSIONS: We found an association between community ILI activity and seasonal variation in all-cause mortality in patients with ESRD, with ILI likely contributing to >1000 deaths annually. Surveillance efforts, such as timely reporting to the CDC of ILI activity within dialysis units during influenza season, may help focus attention on high-risk periods for this vulnerable population.",,"['Gilbertson, David T.', 'Rothman, Kenneth J.', 'Chertow, Glenn M.', 'Bradbury, Brian D.', 'Brookhart, M. Alan', 'Liu, Jiannong', 'Winkelmayer, Wolfgang C.', 'Stürmer, Til', 'Monda, Keri L.', 'Herzog, Charles A.', 'Ashfaq, Akhtar', 'Collins, Allan J.', 'Wetmore, James B.']",,,,
,PMC,IL-27 targets Foxp3(+) Tregs to mediate antiinflammatory functions during experimental allergic airway inflammation,http://dx.doi.org/10.1172/jci.insight.123216,PMC6413774,,,"Foxp3(+) CD4 Tregs are central regulators of inflammation, including allergic inflammation in the lung. There is increasing evidence that inflammatory factors undermine adequate Treg functions and homeostasis, resulting in prolonged and exacerbated inflammation. Therefore, identifying the factors is of the utmost important. IL-27 is an antiinflammatory cytokine implicated in immune regulation and tolerance. However, the cellular mechanisms underlying IL-27–mediated immune regulation in vivo remain largely unknown. Utilizing a cockroach antigen–induced allergic inflammation model in mice, we sought to test the roles of Tregs during IL-27–mediated regulation of allergic inflammation. Intranasally delivered IL-27 significantly reduced the development of airway inflammation. Unexpectedly, the IL-27–induced reduction occurred only in the presence of Tregs. Il27ra(–/–) and Treg-specific Il27ra(–/–) mice developed severe airway inflammation, and IL-27 treatment had little impact on diminishing the inflammatory responses. IL-27–induced treatment was restored following transfer of WT Tregs but not of Tregs deficient in Lag3, a molecule induced by IL-27 in Tregs. Finally, Tregs from asthmatic patients exhibited blunted STAT1 phosphorylation following IL-27 stimulation. Taken together, our results uncover that Tregs are the primary target cells of IL-27 in vivo to mediate its antiinflammatory functions, suggesting that altered IL-27 responsiveness in Tregs may underlie inadequate Treg functions and perpetuation of inflammation.",,"['Nguyen, Quang Tam', 'Jang, Eunjung', 'Le, Hongnga T.', 'Kim, Sohee', 'Kim, Dongkyun', 'Dvorina, Nina', 'Aronica, Mark A.', 'Baldwin, William M.', 'Asosingh, Kewal', 'Comhair, Suzy', 'Min, Booki']",,,,
,PMC,Human coronaviruses OC43 and HKU1 bind to 9-O-acetylated sialic acids via a conserved receptor-binding site in spike protein domain A,http://dx.doi.org/10.1073/pnas.1809667116,PMC6377473,,,"Human betacoronaviruses OC43 and HKU1 are endemic respiratory pathogens and, while related, originated from independent zoonotic introductions. OC43 is in fact a host-range variant of the species Betacoronavirus-1, and more closely related to bovine coronavirus (BCoV)—its presumptive ancestor—and porcine hemagglutinating encephalomyelitis virus (PHEV). The β1-coronaviruses (β1CoVs) and HKU1 employ glycan-based receptors carrying 9-O-acetylated sialic acid (9-O-Ac-Sia). Receptor binding is mediated by spike protein S, the main determinant of coronavirus host specificity. For BCoV, a crystal structure for the receptor-binding domain S1(A) is available and for HKU1 a cryoelectron microscopy structure of the complete S ectodomain. However, the location of the receptor-binding site (RBS), arguably the single-most important piece of information, is unknown. Here we solved the 3.0-Å crystal structure of PHEV S1(A). We then took a comparative structural analysis approach to map the β1CoV S RBS, using the general design of 9-O-Ac-Sia-binding sites as blueprint, backed-up by automated ligand docking, structure-guided mutagenesis of OC43, BCoV, and PHEV S1(A), and infectivity assays with BCoV-S–pseudotyped vesicular stomatitis viruses. The RBS is not exclusive to OC43 and related animal viruses, but is apparently conserved and functional also in HKU1 S1(A). The binding affinity of the HKU1 S RBS toward short sialoglycans is significantly lower than that of OC43, which we attribute to differences in local architecture and accessibility, and which may be indicative for differences between the two viruses in receptor fine-specificity. Our findings challenge reports that would map the OC43 RBS elsewhere in S1(A) and that of HKU1 in domain S1(B).",,"['Hulswit, Ruben J. G.', 'Lang, Yifei', 'Bakkers, Mark J. G.', 'Li, Wentao', 'Li, Zeshi', 'Schouten, Arie', 'Ophorst, Bram', 'van Kuppeveld, Frank J. M.', 'Boons, Geert-Jan', 'Bosch, Berend-Jan', 'Huizinga, Eric G.', 'de Groot, Raoul J.']",,,,
,PMC,Tripartite motif proteins: an emerging antiviral protein family,http://dx.doi.org/10.2217/fvl-2018-0161,PMC6690340,,,,,"['Patil, Girish', 'Li, Shitao']",,,,
,PMC,Treatment of a Woman With Glycyrrhiza glabra for Acute Sinusitis: A Case Report,http://dx.doi.org/10.1016/j.jcm.2018.04.005,PMC6391234,,,"OBJECTIVE: The purpose of this case report is to describe the treatment of a patient with acute sinusitis using Glycyrrhiza glabra. CLINICAL FEATURES: A 26-year-old woman presented with acute sinusitis of 10-day duration. Her symptoms included facial pressure and soreness around the frontal and maxillary sinuses, a headache, pharyngitis, a fever, rhinorrhea, nasal congestion with postnasal drip, a productive cough, myalgias, and fatigue. INTERVENTION AND OUTCOME: After administration of 12 to 15 drops of a 2 000-mg tincture of G glabra twice a day, improvements were noted. Resolution of her symptoms occurred after 3 days of treatment. CONCLUSION: For the treatment of acute sinusitis, G glabra may be a natural therapeutic remedy.",,"['Martin, Brett R.', 'Reshamwala, Gaurav', 'Short, Melanie']",,,,
,PMC,Man and Microbe: Fraternizing with the frenemy,http://dx.doi.org/10.1016/j.mjafi.2018.12.017,PMC6349669,,,,,"Subramanian, Shankar",,,,
,PMC,Local Decision Making for Implementing Social Distancing in Response to Outbreaks,http://dx.doi.org/10.1177/0033354918819755,PMC6410485,,,"OBJECTIVES: Social distancing is the practice of restricting contact among persons to prevent the spread of infection. This study sought to (1) identify key features of preparedness and the primary concerns of local public health officials in deciding to implement social distancing measures and (2) determine whether any particular factor could explain the widespread variation among health departments in responses to past outbreaks. METHODS: We conducted an online survey of health departments in the United States in 2015 to understand factors influencing health departments’ decision making when choosing whether to implement social distancing measures. We paired survey results with data on area population demographic characteristics and analyzed them with a focus on broad trends. RESULTS: Of 600 health departments contacted, 150 (25%) responded. Of these 150 health departments, 63 (42%) indicated that they had implemented social distancing in the past 10 years. Only 10 (7%) health departments had a line-item budget for isolation or quarantine. The most common concern about social distancing was public health impact (n = 62, 41%). Concerns about law, politics, finances, vulnerable populations, and sociocultural issues were each identified by 7% to 10% of health departments. We were unable to clearly predict which factors would influence these decisions. CONCLUSIONS: Variations in the decision to implement social distancing are likely the result of differences in organizational authority and resources and in the primary concerns about implementing social distancing. Research and current social distancing guidelines for health departments should address these factors.",,"['Katz, Rebecca', 'Vaught, Andrea', 'Simmens, Samuel J.']",,,,
,PMC,A Measles Virus-Based Vaccine Candidate Mediates Protection against Zika Virus in an Allogeneic Mouse Pregnancy Model,http://dx.doi.org/10.1128/JVI.01485-18,PMC6340036,,,"The impact of the Zika virus (ZIKV) epidemic highlights the need for vaccines that reduce or prevent infection and reliably prevent teratogenic complications. The live-attenuated measles virus (MV) vaccine strains are a promising vaccine platform, since they induce robust humoral and cellular immune responses against additional antigens and have an excellent safety record. To explore its potential to protect against ZIKV, we compared a recombinant Schwarz strain MV that encodes ZIKV prM and soluble E proteins (MV-Zika-sE) with a prototypic alum-adjuvanted whole inactivated ZIKV particle vaccine. Analysis of MV-Zika-sE-infected cells confirmed antigen expression, and the virus replicated with vaccine strain characteristics. Immunized IFNAR(−/−)-CD46Ge mice developed E protein-specific and neutralizing antibodies, and ZIKV E-specific cellular immune responses were observed by gamma interferon (IFN-γ) enzyme-linked immunospot (ELISpot) and in vitro T cell proliferation assays. To analyze protective efficacy, vaccinated female mice were challenged with ZIKV after allogeneic mating. In MV-Zika-sE-vaccinated mice, weight gain was similar to that in uninfected mice, while no plasma viremia was detectable in the majority of the animals. In contrast, infected control animals gained less weight and experienced about 100-fold higher viremia over at least 3 days. Moreover, vaccination with MV-Zika-sE reduced the ZIKV load in different organs and the placentas and prevented infection of the fetus. Consequently, no fetal growth retardation, anemia, or death due to ZIKV infection was seen in MV-Zika-sE-vaccinated dams. In contrast, the inactivated ZIKV vaccine had little to no effect in our studies. Therefore, the MV-derived ZIKV vaccine is a promising candidate for further preclinical and clinical development. IMPORTANCE Zika virus (ZIKV) is a mosquito-borne flavivirus that causes a variety of neurological complications, including congenital birth defects. Despite the urgent need, no ZIKV vaccine has yet been licensed. Recombinant vaccine strain-derived measles viruses (MV) constitute a promising vector platform to induce immunity against foreign pathogens by expressing antigens from additional transcription units while at the same time possessing a remarkable safety profile. This concept has already been validated against different pathogens, including at least 3 other flaviviruses, and our data show that vaccination with MV expressing soluble ZIKV E protein significantly diminishes infection and prevents fetal loss or damage in an allogeneic mouse pregnancy model. It can thus be regarded as a promising emergency vaccine candidate with the potential for inclusion in routine vaccination settings in areas of endemicity to prevent teratogenic effects of circulating ZIKV during pregnancy, comparable to standard rubella virus vaccination.",,"['Nürnberger, Cindy', 'Bodmer, Bianca S.', 'Fiedler, Anna H.', 'Gabriel, Gülsah', 'Mühlebach, Michael D.']",,,,
,PMC,Real-time 2-5A kinetics suggest that interferons β and λ evade global arrest of translation by RNase L,http://dx.doi.org/10.1073/pnas.1818363116,PMC6369740,,,"Cells of all mammals recognize double-stranded RNA (dsRNA) as a foreign material. In response, they release interferons (IFNs) and activate a ubiquitously expressed pseudokinase/endoribonuclease RNase L. RNase L executes regulated RNA decay and halts global translation. Here, we developed a biosensor for 2′,5′-oligoadenylate (2-5A), the natural activator of RNase L. Using this biosensor, we found that 2-5A was acutely synthesized by cells in response to dsRNA sensing, which immediately triggered cellular RNA cleavage by RNase L and arrested host protein synthesis. However, translation-arrested cells still transcribed IFN-stimulated genes and secreted IFNs of types I and III (IFN-β and IFN-λ). Our data suggest that IFNs escape from the action of RNase L on translation. We propose that the 2-5A/RNase L pathway serves to rapidly and accurately suppress basal protein synthesis, preserving privileged production of defense proteins of the innate immune system.",,"['Chitrakar, Alisha', 'Rath, Sneha', 'Donovan, Jesse', 'Demarest, Kaitlin', 'Li, Yize', 'Sridhar, Raghavendra Rao', 'Weiss, Susan R.', 'Kotenko, Sergei V.', 'Wingreen, Ned S.', 'Korennykh, Alexei']",,,,
,PMC,Genotype Tailored Treatment of Mild Symptomatic Acid Reflux in Children with Uncontrolled Asthma (GenARA): Rationale and Methods,http://dx.doi.org/10.1016/j.cct.2019.01.009,PMC7039713,,,"Asthma causes enormous suffering and cost for children in the US and around the world [1-3]. Co-morbid gastroesophageal reflux disease (GERD) makes asthma management more difficult due to increased symptoms. Proton pump inhibitor (PPI) drugs are effective at improving to GERD symptoms, however they have demonstrated only modest and variable effects on asthma control in the setting of co-morbid GERD. Importantly, PPI metabolism and efficacy depend on CYP2C19 genotype. The Genotype Tailored Treatment of Symptomatic Acid Reflux in Children with Uncontrolled Asthma (GenARA) study is a randomized, double-blind, placebo-controlled trial to determine if genotype-tailored PPI dosing improves asthma symptoms among children with inadequately controlled asthma and GERD symptoms. This study has an innovative design to both assess the efficacy of genotype-tailored PPI dosing and perform pharmacokinetic modeling of the oral PPI Lansoprazole. Children ages 6-17 years old with clinician-diagnosed asthma and mild GERD symptoms will submit a saliva sample for CYP2C19 genotyping. Participants will undergo a two-step randomization to: (1) genotype-tailored versus conventional dosing of open-label oral lansoprazole for pharmacokinetic modeling, and (2) genotype-tailored lansoprazole daily versus placebo for 24 weeks to determine the effect of genotype-tailored PPI dosing on asthma control. Measures of asthma control, spirometry, and nasal washes during acute illnesses will be collected at 8-week intervals throughout the study. GenARA will better define the effects of CYP2C19 genotype on the dose response of lansoprazole in children and adolescents and assess if a novel dosing regimen improves GERD and asthma control.",,"['Tang, Monica', 'Blake, Kathryn V.', 'Lima, John J.', 'Mougey, Edward B.', 'Franciosi, James', 'Schmidt, Stephan', 'Hossain, Md Jobayer', 'Cobbaert, Marjan', 'Fischer, Bernard M.', 'Lang, Jason E.']",,,,
,PMC,"Plasmacytoid dendritic cells: development, regulation and function",http://dx.doi.org/10.1016/j.immuni.2018.12.027,PMC6342491,,,"Plasmacytoid dendritic cells (pDCs) are a unique sentinel cell type that can detect pathogen-derived nucleic acids and respond with rapid and massive production of type I interferon. This review summarizes our current understanding of pDC biology, including transcriptional regulation, heterogeneity, role in antiviral immune responses, and involvement in immune pathology, particularly in autoimmune diseases, immunodeficiency and cancer. We also highlight the remaining gaps in our knowledge and important questions for the field, such as the molecular basis of unique interferon-producing capacity of pDCs. A better understanding of cell type-specific positive and negative control of pDC function should pave the way for translational applications focused on this immune cell type.",,"Reizis, Boris",,,,
,PMC,Period of Measurement in Time-Series Predictions of Disease Counts from 2007 to 2017 in Northern Nevada: Analytics Experiment,http://dx.doi.org/10.2196/11357,PMC6350093,30664479,CC BY,"BACKGROUND: The literature in statistics presents methods by which autocorrelation can identify the best period of measurement to improve the performance of a time-series prediction. The period of measurement plays an important role in improving the performance of disease-count predictions. However, from the operational perspective in public health surveillance, there is a limitation to the length of the measurement period that can offer meaningful and valuable predictions. OBJECTIVE: This study aimed to establish a method that identifies the shortest period of measurement without significantly decreasing the prediction performance for time-series analysis of disease counts. METHODS: The data used in this evaluation include disease counts from 2007 to 2017 in northern Nevada. The disease counts for chlamydia, salmonella, respiratory syncytial virus, gonorrhea, viral meningitis, and influenza A were predicted. RESULTS: Our results showed that autocorrelation could not guarantee the best performance for prediction of disease counts. However, the proposed method with the change-point analysis suggests a period of measurement that is operationally acceptable and performance that is not significantly different from the best prediction. CONCLUSIONS: The use of change-point analysis with autocorrelation provides the best and most practical period of measurement.",2019 Jan 15,"['Talaei-Khoei, Amir', 'Wilson, James M', 'Kazemi, Seyed-Farzan']",JMIR Public Health Surveill,,,
,PMC,Rice stripe virus hitchhikes the vector insect vitellogenin ligand-receptor pathway for ovary entry,http://dx.doi.org/10.1098/rstb.2018.0312,PMC6367155,,,"It is known that plant arboviruses infect insect vector cells by endocytosis; however, the cellular receptors that mediate endocytosis have not been well defined. In our recently published work and this study, by clarifying the vertical transmission mechanism of Rice stripe virus (RSV) in Laodelphax striatellus, we provide a novel paradigm for how arboviruses enter insect germ-line cells. Instead of direct interaction with a viral receptor, the virus binds to a secreted ligand protein, hitchhiking the ligand-receptor pathway to achieve cell entry. Vitellogenin (Vg) is an indispensable protein for embryo development that is synthesized extra-ovarially and taken up by germ-line cells through Vg receptor (VgR)-mediated endocytosis. After revealing that RSV invades L. striatellus ovary by a specific molecular interaction with the insect Vg in haemolymph, this study addressed VgR's function in mediating the RSV invasion of the germarium nurse cells, further confirming the ligand's receptor-mediated viral cell-invasion mechanism. Understanding the viral ovary-entry pathways in vectors will help to find suitable measures to block the trans-generation transmission of the viruses. This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management’.",,"['Huo, Yan', 'Yu, Yuanling', 'Liu, Qing', 'Liu, Da', 'Zhang, Mengting', 'Liang, Jingnan', 'Chen, Xiaoying', 'Zhang, Lili', 'Fang, Rongxiang']",,,,
,PMC,Rational Design and In Vivo Characterization of Vaccine Adjuvants,http://dx.doi.org/10.1093/ilar/ily018,PMC6927902,,,"Many different adjuvants are currently being developed for subunit vaccines against a number of pathogens and diseases. Rational design is increasingly used to develop novel vaccine adjuvants, which requires extensive knowledge of, for example, the desired immune responses, target antigen-presenting cell subsets, their localization, and expression of relevant pattern-recognition receptors. The adjuvant mechanism of action and efficacy are usually evaluated in animal models, where mice are by far the most used. In this review, we present methods for assessing adjuvant efficacy and function in animal models: (1) whole-body biodistribution evaluated by using fluorescently and radioactively labeled vaccine components; (2) association and activation of immune cell subsets at the injection site, in the draining lymph node, and the spleen; (4) adaptive immune responses, such as cytotoxic T-lymphocytes, various T-helper cell subsets, and antibody responses, which may be quantitatively evaluated using ELISA, ELISPOT, and immunoplex assays and qualitatively evaluated using flow cytometric and single cell sequencing assays; and (5) effector responses, for example, antigen-specific cytotoxic potential of CD8(+) T cells and antibody neutralization assays. While the vaccine-induced immune responses in mice often correlate with the responses induced in humans, there are instances where immune responses detected in mice are not translated to the human situation. We discuss some examples of correlation and discrepancy between mouse and human immune responses and how to understand them.",,"['Schmidt, Signe Tandrup', 'Pedersen, Gabriel Kristian', 'Christensen, Dennis']",,,,
,PMC,Chemokine CXCL10 and Coronavirus-Induced Neurologic Disease,http://dx.doi.org/10.1089/vim.2018.0073,PMC6350065,,,"Chemokines (chemotactic cytokines) are involved in a wide variety of biological processes. Following microbial infection, there is often robust chemokine signaling elicited from infected cells, which contributes to both innate and adaptive immune responses that control growth of the invading pathogen. Infection of the central nervous system (CNS) by the neuroadapted John Howard Mueller (JHM) strain of mouse hepatitis virus (JHMV) provides an excellent example of how chemokines aid in host defense as well as contribute to disease. Intracranial inoculation of the CNS of susceptible mice with JHMV results in an acute encephalomyelitis characterized by widespread dissemination of virus throughout the parenchyma. Virus-specific T cells are recruited to the CNS, and control viral replication through release of antiviral cytokines and cytolytic activity. Sterile immunity is not acquired, and virus will persist primarily in white matter tracts leading to chronic neuroinflammation and demyelination. Chemokines are expressed and contribute to defense as well as chronic disease by attracting targeted populations of leukocytes to the CNS. The T cell chemoattractant chemokine CXCL10 (interferon-inducible protein 10 kDa, IP-10) is prominently expressed in both stages of disease, and serves to attract activated T and B lymphocytes expressing CXC chemokine receptor 3 (CXCR3), the receptor for CXCL10. Functional studies that have blocked expression of either CXCL10 or CXCR3 illuminate the important role of this signaling pathway in host defense and neurodegeneration in a model of viral-induced neurologic disease.",,"['Skinner, Dominic', 'Marro, Brett S.', 'Lane, Thomas E.']",,,,
,PMC,Understanding the Role of Antiviral Cytokines and Chemokines on Neural Stem/Progenitor Cell Activity and Survival,http://dx.doi.org/10.1089/vim.2018.0091,PMC6350063,,,"Viral infections of the central nervous system are accompanied by the expression of cytokines and chemokines that can be critical for the control of viral replication in the brain. The outcomes of cytokine/chemokine signaling in neural cells vary widely, with cell-specific effects on cellular activity, proliferation, and survival. Neural stem/progenitor cells (NSPCs) are often altered during viral infections, through direct infection by the virus or by the influence of immune cell activity or cytokine/chemokine signaling. However, it has been challenging to dissect the contribution of the virus and specific inflammatory mediators during an infection. In addition to initiating an antiviral program in infected NSPCs, cytokines/chemokines can induce multiple changes in NSPC behavior that can perturb NSPC numbers, differentiation into other neural cells, and migration to sites of injury, and ultimately brain development and repair. The focus of this review was to dissect the effects of common antiviral cytokines and chemokines on NSPC activity, and to consider the subsequent pathological consequences for the host from changes in NSPC function.",,"['Chandwani, Manisha N.', 'Creisher, Patrick S.', ""O'Donnell, Lauren A.""]",,,,
,PMC,Intercellular Communication Is Key for Protective IFNα/β Signaling During Viral Central Nervous System Infection,http://dx.doi.org/10.1089/vim.2018.0101,PMC6350053,,,"A variety of viruses can induce central nervous system (CNS) infections and neurological diseases, although the incidence is rare. Similar to peripheral infections, IFNα/β induction and signaling constitutes a first line of defense to limit virus dissemination. However, CNS-resident cells differ widely in their repertoire and magnitude of both basal and inducible components in the IFNα/β pathway. While microglia as resident myeloid cells have been implicated as prominent sentinels of CNS invading pathogens or insults, astrocytes are emerging as key responders to many neurotropic RNA virus infections. Focusing on RNA viruses, this review discusses the role of astrocytes as IFNα/β inducers and responders and touches on the role of IFNα/β receptor signaling in regulating myeloid cell activation and IFNγ responsiveness. A summary picture emerges implicating IFNα/β not only as key in establishing the classical “antiviral” state, but also orchestrating cell mobility and IFNγ-mediated effector functions.",,"['Hwang, Mihyun', 'Bergmann, Cornelia C.']",,,,
,PMC,Alterations in sialic-acid O-acetylation glycoforms during murine erythrocyte development,http://dx.doi.org/10.1093/glycob/cwy110,PMC6381321,,,"We used Casd1-deficient mice to confirm that this enzyme is responsible for 9-O-acetylation of sialic acids in vivo. We observed a complete loss of 9-O-acetylation of sialic acid on the surface of myeloid, erythroid and CD4(+) T cells in Casd1-deficient mice. Although 9-O-acetylation of sialic acids on multiple hematopoietic lineages was lost, there were no obvious defects in hematopoiesis. Interestingly, erythrocytes from Casd1-deficient mice also lost reactivity to TER-119, a rat monoclonal antibody that is widely used to mark the murine erythroid lineage. The sialic acid glyco-epitope recognized by TER-119 on erythrocytes was sensitive to the sialic acid O-acetyl esterase activity of the hemagglutinin-esterase from bovine coronavirus but not to the corresponding enzyme from the influenza C virus. During erythrocyte development, TER-119(+) Ery-A and Ery-B cells could be stained by catalytically inactive bovine coronavirus hemagglutinin-esterase but not by the inactive influenza C hemagglutinin-esterase, while TER-119(+) Ery-C cells and mature erythrocytes were recognized by both virolectins. Although the structure of the sialoglycoconjugate recognized by TER-119 was not chemically demonstrated, its selective binding to virolectins suggests that it may be comprised of a 7,9-di-O-acetyl form of sialic acid. As erythrocytes mature, the surfaces of Ery-C cells and mature erythrocytes also acquire an additional distinct CASD1-dependent 9-O-acetyl sialic acid moiety that can be recognized by virolectins from both influenza C and bovine coronavirus.",,"['Mahajan, Vinay S', 'Alsufyani, Faisal', 'Mattoo, Hamid', 'Rosenberg, Ian', 'Pillai, Shiv']",,,,
,PMC,Instructions for Authors,http://dx.doi.org/10.1097/01.CM9.0000552938.90616.59,PMC6629299,,,,,,,,,
,PMC,Structure of interferon-stimulated gene product 15 (ISG15) from the bat species Myotis davidii and the impact of interdomain ISG15 interactions on viral protein engagement,http://dx.doi.org/10.1107/S2059798318015322,PMC6333284,,,"Bats have long been observed to be the hosts and the origin of numerous human diseases. Bats, like all mammals, rely on a number of innate immune mechanisms to combat invading pathogens, including the interferon type I, II and III responses. Ubiquitin-like interferon-stimulated gene product 15 (ISG15) is a key modulator of these interferon responses. Within these pathways, ISG15 can serve to stabilize host proteins modulating innate immune responses and act as a cytokine. Post-translational modifications of viral proteins introduced by ISG15 have also been observed to directly affect the function of numerous viral proteins. Unlike ubiquitin, which is virtually identical across all animals, comparison of ISG15s across species reveals that they are relatively divergent, with sequence identity dropping to as low as ∼58% among mammals. In addition to serving as an obstacle to the zoonotic transmission of influenza, these ISG15 species–species differences have also long been shown to have an impact on the function of viral deISGylases. Recently, the structure of the first nonhuman ISG15, originating from mouse, suggested that the structures of human ISG15 may not be reflective of other species. Here, the structure of ISG15 from the bat species Myotis davidii solved to 1.37 Å resolution is reported. Comparison of this ISG15 structure with those from human and mouse not only underscores the structural impact of ISG15 species–species differences, but also highlights a conserved hydrophobic motif formed between the two domains of ISG15. Using the papain-like deISGylase from Severe acute respiratory syndrome coronavirus as a probe, the biochemical importance of this motif in ISG15–protein engagements was illuminated.",,"['Langley, Caroline', 'Goodwin, Octavia', 'Dzimianski, John V.', 'Daczkowski, Courtney M.', 'Pegan, Scott D.']",,,,
,PMC,Isolation and Characterization of a Distinct Influenza A Virus from Egyptian Bats,http://dx.doi.org/10.1128/JVI.01059-18,PMC6321940,,,"Recently, two genetically distinct influenza viruses were detected in bats in Guatemala and Peru. We conducted influenza A virus surveillance among four bat species in Egypt. Out of 1,202 swab specimens, 105 were positive by real-time PCR. A virus was successfully isolated in eggs and propagated in MDCK cells in the presence of N-tosyl-l-phenylalanine chloromethyl ketone-treated trypsin. Genomic analysis revealed that the virus was phylogenetically distinct from all other influenza A viruses. Analysis of the hemagglutinin gene suggested a common ancestry with other H9 viruses, and the virus showed a low level of cross-reactivity with serum raised against H9N2 viruses. Bats were seropositive for the isolated viruses. The virus replicated in the lungs of experimentally infected mice. While it is genetically distinct, this virus shares several avian influenza virus characteristics suggesting a more recent avian host origin. IMPORTANCE Through surveillance, we isolated and characterized an influenza A virus from Egyptian fruit bats. This virus had an affinity to avian-like receptors but was also able to infect mice. Our findings indicate that bats may harbor a diversity of influenza A viruses. Such viruses may have the potential to cross the species barrier to infect other species, including domestic birds, mammals, and, possibly, humans.",,"['Kandeil, Ahmed', 'Gomaa, Mokhtar R.', 'Shehata, Mahmoud M.', 'El Taweel, Ahmed N.', 'Mahmoud, Sara H.', 'Bagato, Ola', 'Moatasim, Yassmin', 'Kutkat, Omnia', 'Kayed, Ahmed S.', 'Dawson, Patrick', 'Qiu, Xueting', 'Bahl, Justin', 'Webby, Richard J.', 'Karesh, William B.', 'Kayali, Ghazi', 'Ali, Mohamed A.']",,,,
,PMC,The NS1 Protein of Influenza A Virus Participates in Necroptosis by Interacting with MLKL and Increasing Its Oligomerization and Membrane Translocation,http://dx.doi.org/10.1128/JVI.01835-18,PMC6321931,,,"Elimination of infected cells by programmed cell death is a well-recognized host defense mechanism to control the spread of infection. In addition to apoptosis, necroptosis is also one of the mechanisms of cell death that can be activated by viral infection. Activation of necroptosis leads to the phosphorylation of mixed-lineage kinase domain-like protein (MLKL) by receptor-interacting protein kinase 3 (RIPK3) and results in MLKL oligomerization and membrane translocation, leading to membrane disruption and a loss of cellular ion homeostasis. It has recently been reported that influenza A virus (IAV) infection induces necroptosis. However, the underlying mechanism of the IAV-mediated necroptosis process, particularly the roles of IAV proteins in necroptosis, remains unexplored. Here, we report that IAV infection induces necroptosis in macrophages and epithelial cells. We demonstrate that the NS1 protein of IAV interacts with MLKL. Coiled-coil domain 2 of MLKL has a predominant role in mediating the MLKL interaction with NS1. The interaction of NS1 with MLKL increases MLKL oligomerization and membrane translocation. Moreover, the MLKL-NS1 interaction enhances MLKL-mediated NLRP3 inflammasome activation, leading to increased interleukin-1β (IL-1β) processing and secretion. IMPORTANCE Necroptosis is a programmed cell death that is inflammatory in nature owing to the release of danger-associated molecular patterns from the ruptured cell membrane. However, necroptosis also constitutes an important arm of host immune responses. Thus, a balanced inflammatory response determines the disease outcome. We report that the NS1 protein of IAV participates in necroptosis by interacting with MLKL, resulting in increased MLKL oligomerization and membrane translocation. These results reveal a novel function of the NS1 protein and the mechanism by which IAV induces necroptosis. Moreover, we show that this interaction enhances NLRP3 inflammasome activation and IL-1β processing and secretion. This information may contribute to a better understanding of the role of necroptosis in IAV-induced inflammation.",,"['Gaba, Amit', 'Xu, Fang', 'Lu, Yao', 'Park, Hong-Su', 'Liu, GuanQun', 'Zhou, Yan']",,,,
,PMC,Mutations in Influenza A Virus Neuraminidase and Hemagglutinin Confer Resistance against a Broadly Neutralizing Hemagglutinin Stem Antibody,http://dx.doi.org/10.1128/JVI.01639-18,PMC6321927,,,"Influenza A virus (IAV), a major cause of human morbidity and mortality, continuously evolves in response to selective pressures. Stem-directed, broadly neutralizing antibodies (sBnAbs) targeting the influenza virus hemagglutinin (HA) are a promising therapeutic strategy, but neutralization escape mutants can develop. We used an integrated approach combining viral passaging, deep sequencing, and protein structural analyses to define escape mutations and mechanisms of neutralization escape in vitro for the F10 sBnAb. IAV was propagated with escalating concentrations of F10 over serial passages in cultured cells to select for escape mutations. Viral sequence analysis revealed three mutations in HA and one in neuraminidase (NA). Introduction of these specific mutations into IAV through reverse genetics confirmed their roles in resistance to F10. Structural analyses revealed that the selected HA mutations (S123G, N460S, and N203V) are away from the F10 epitope but may indirectly impact influenza virus receptor binding, endosomal fusion, or budding. The NA mutation E329K, which was previously identified to be associated with antibody escape, affects the active site of NA, highlighting the importance of the balance between HA and NA function for viral survival. Thus, whole-genome population sequencing enables the identification of viral resistance mutations responding to antibody-induced selective pressure. IMPORTANCE Influenza A virus is a public health threat for which currently available vaccines are not always effective. Broadly neutralizing antibodies that bind to the highly conserved stem region of the influenza virus hemagglutinin (HA) can neutralize many influenza virus strains. To understand how influenza virus can become resistant or escape such antibodies, we propagated influenza A virus in vitro with escalating concentrations of antibody and analyzed viral populations by whole-genome sequencing. We identified HA mutations near and distal to the antibody binding epitope that conferred resistance to antibody neutralization. Additionally, we identified a neuraminidase (NA) mutation that allowed the virus to grow in the presence of high concentrations of the antibody. Virus carrying dual mutations in HA and NA also grew under high antibody concentrations. We show that NA mutations mediate the escape of neutralization by antibodies against HA, highlighting the importance of a balance between HA and NA for optimal virus function.",,"['Prachanronarong, Kristina L.', 'Canale, Aneth S.', 'Liu, Ping', 'Somasundaran, Mohan', 'Hou, Shurong', 'Poh, Yu-Ping', 'Han, Thomas', 'Zhu, Quan', 'Renzette, Nicholas', 'Zeldovich, Konstantin B.', 'Kowalik, Timothy F.', 'Kurt-Yilmaz, Nese', 'Jensen, Jeffrey D.', 'Bolon, Daniel N. A.', 'Marasco, Wayne A.', 'Finberg, Robert W.', 'Schiffer, Celia A.', 'Wang, Jennifer P.']",,,,
,PMC,Functional Mapping of Regions Involved in the Negative Imprinting of Virion Particle Infectivity and in Target Cell Protection by Interferon-Induced Transmembrane Protein 3 against HIV-1,http://dx.doi.org/10.1128/JVI.01716-18,PMC6321926,,,"The interferon-induced transmembrane proteins (IFITMs) are a family of highly related antiviral factors that affect numerous viruses at two steps: in target cells by sequestering incoming viruses in endosomes and in producing cells by leading to the production of virions that package IFITMs and exhibit decreased infectivity. While most studies have focused on the former, little is known about the regulation of the negative imprinting of virion particle infectivity by IFITMs and about its relationship with target cell protection. Using a panel of IFITM3 mutants against HIV-1, we have explored these issues as well as others related to the biology of IFITM3, in particular virion packaging, stability, the relation to CD63/multivesicular bodies (MVBs), the modulation of cholesterol levels, and the relationship between negative imprinting of virions and target cell protection. The results that we have obtained exclude a role for cholesterol and indicate that CD63 accumulation does not directly relate to an antiviral behavior. We have defined regions that modulate the two antiviral properties of IFITM3 as well as novel domains that modulate protein stability and that, in so doing, influence the extent of its packaging into virions. The results that we have obtained, however, indicate that, even in the context of an IFITM-susceptible virus, IFITM3 packaging is not sufficient for negative imprinting. Finally, while most mutations concomitantly affect target cell protection and negative imprinting, a region in the C-terminal domain (CTD) exhibits a differential behavior, potentially highlighting the regulatory role that this domain may play in the two antiviral activities of IFITM3. IMPORTANCE IFITM proteins have been associated with the sequestration of incoming virions in endosomes (target cell protection) and with the production of virion particles that incorporate IFITMs and exhibit decreased infectivity (negative imprinting of virion infectivity). How the latter is regulated and whether these two antiviral properties are related remain unknown. By examining the behavior of a large panel of IFITM3 mutants against HIV-1, we determined that IFITM3 mutants are essentially packaged into virions proportionally to their intracellular levels of expression. However, even in the context of an IFITM-susceptible virus, IFITM3 packaging is not sufficient for the antiviral effects. Most mutations were found to concomitantly affect both antiviral properties of IFITM3, but one CTD mutant exhibited a divergent behavior, possibly highlighting a novel regulatory role for this domain. These findings thus advance our comprehension of how this class of broad antiviral restriction factors acts.",,"['Appourchaux, Romain', 'Delpeuch, Mathilde', 'Zhong, Li', 'Burlaud-Gaillard, Julien', 'Tartour, Kevin', 'Savidis, George', 'Brass, Abraham', 'Etienne, Lucie', 'Roingeard, Philippe', 'Cimarelli, Andrea']",,,,
,PMC,Mutations in the Spike Protein of Middle East Respiratory Syndrome Coronavirus Transmitted in Korea Increase Resistance to Antibody-Mediated Neutralization,http://dx.doi.org/10.1128/JVI.01381-18,PMC6321919,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) poses a threat to public health. The virus is endemic in the Middle East but can be transmitted to other countries by travel activity. The introduction of MERS-CoV into the Republic of Korea by an infected traveler resulted in a hospital outbreak of MERS that entailed 186 cases and 38 deaths. The MERS-CoV spike (S) protein binds to the cellular protein DPP4 via its receptor binding domain (RBD) and mediates viral entry into target cells. During the MERS outbreak in Korea, emergence and spread of viral variants that harbored mutations in the RBD, D510G and I529T, was observed. Counterintuitively, these mutations were found to reduce DPP4 binding and viral entry into target cells. In this study, we investigated whether they also exerted proviral effects. We confirm that changes D510G and I529T reduce S protein binding to DPP4 but show that this reduction only translates into diminished viral entry when expression of DPP4 on target cells is low. Neither mutation modulated S protein binding to sialic acids, S protein activation by host cell proteases, or inhibition of S protein-driven entry by interferon-induced transmembrane proteins. In contrast, changes D510G and I529T increased resistance of S protein-driven entry to neutralization by monoclonal antibodies and sera from MERS patients. These findings indicate that MERS-CoV variants with reduced neutralization sensitivity were transmitted during the Korean outbreak and that the responsible mutations were compatible with robust infection of cells expressing high levels of DPP4. IMPORTANCE MERS-CoV has pandemic potential, and it is important to identify mutations in viral proteins that might augment viral spread. In the course of a large hospital outbreak of MERS in the Republic of Korea in 2015, the spread of a viral variant that contained mutations in the viral spike protein was observed. These mutations were found to reduce receptor binding and viral infectivity. However, it remained unclear whether they also exerted proviral effects. We demonstrate that these mutations reduce sensitivity to antibody-mediated neutralization and are compatible with robust infection of target cells expressing large amounts of the viral receptor DPP4.",,"['Kleine-Weber, Hannah', 'Elzayat, Mahmoud Tarek', 'Wang, Lingshu', 'Graham, Barney S.', 'Müller, Marcel A.', 'Drosten, Christian', 'Pöhlmann, Stefan', 'Hoffmann, Markus']",,,,
,PMC,Deletion of both the Tyrosine-Based Endocytosis Signal and the Endoplasmic Reticulum Retrieval Signal in the Cytoplasmic Tail of Spike Protein Attenuates Porcine Epidemic Diarrhea Virus in Pigs,http://dx.doi.org/10.1128/JVI.01758-18,PMC6321913,,,"Porcine epidemic diarrhea virus (PEDV) causes high mortality in neonatal piglets. The PEDV spike (S) protein contains two intracellular sorting motifs, YxxΦ (tyrosine-based motif YEVF or YEAF) and KVHVQ at the cytoplasmic tail, yet their functions have not been fully elucidated. Some Vero cell-adapted and/or attenuated PEDV variants contain ablations in these two motifs. We hypothesized that these motifs contribute to viral pathogenicity. By transiently expressing PEDV S proteins with mutations in the motifs, we confirmed that the motif KVHVQ is involved in retention of the S proteins in the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC). In addition, we showed that the YxxΦ motif triggers endocytosis of S proteins. These two motifs synergistically regulate the level of S expressed on the cell surface. To investigate their role in viral pathogenicity, we generated three recombinant PEDVs by introducing deletions or a mutation in the two motifs of the infectious clone of PEDV PC22A strain (icPC22A): (i) icΔ10aa (ΔYxxΦEKVHVQ), (ii) icΔ5aa (ΔKVHVQ), and (iii) icYA (Y1378A, to an inactivated motif, AEVF). Infection of Vero cells with icΔ10aa resulted in larger syncytia and more virions, with reduced numbers of S protein projections on the surface compared with icPC22A. Furthermore, we orally inoculated five groups of 5-day-old gnotobiotic piglets with the three mutants, icPC22A, or a mock treatment. Mutant icΔ10aa caused less severe diarrhea rate and significantly milder intestinal lesions than icPC22A, icΔ5aa, and icYA. These data suggest that the deletion of both motifs can reduce the virulence of PEDV in piglets. IMPORTANCE Many coronaviruses (CoVs) possess conserved motifs YxxΦ and/or KxHxx/KKxx in the cytoplasmic tail of the S protein. The KxHxx/KKxx motif has been identified as the ER retrieval signal, but the function of the YxxΦ motif in the intracellular sorting of CoV S proteins remains controversial. In this study, we showed that the YxxΦ of PEDV S protein is an endocytosis signal. Furthermore, using reverse genetics technology, we evaluated its role in PEDV pathogenicity in neonatal piglets. Our results explain one attenuation mechanism of Vero cell-adapted PEDV variants lacking functional YxxΦ and KVHVQ motifs. Knowledge from this study may aid in the design of efficacious live attenuated vaccines against PEDV, as well as other CoVs bearing the same motif in their S protein.",,"['Hou, Yixuan', 'Meulia, Tea', 'Gao, Xiang', 'Saif, Linda J.', 'Wang, Qiuhong']",,,,
,PMC,Foot-and-Mouth Disease Virus Leader Protease Cleaves G3BP1 and G3BP2 and Inhibits Stress Granule Formation,http://dx.doi.org/10.1128/JVI.00922-18,PMC6321903,,,"Like other viruses, the picornavirus foot-and-mouth disease virus (FMDV; genus Aphthovirus), one of the most notorious pathogens in the global livestock industry, needs to navigate antiviral host responses to establish an infection. There is substantial insight into how FMDV suppresses the type I interferon (IFN) response, but it is largely unknown whether and how FMDV modulates the integrated stress response. Here, we show that the stress response is suppressed during FMDV infection. Using a chimeric recombinant encephalomyocarditis virus (EMCV), in which we functionally replaced the endogenous stress response antagonist by FMDV leader protease (L(pro)) or 3C(pro), we demonstrate an essential role for L(pro) in suppressing stress granule (SG) formation. Consistently, infection with a recombinant FMDV lacking L(pro) resulted in SG formation. Additionally, we show that L(pro) cleaves the known SG scaffold proteins G3BP1 and G3BP2 but not TIA-1. We demonstrate that the closely related equine rhinitis A virus (ERAV) L(pro) also cleaves G3BP1 and G3BP2 and also suppresses SG formation, indicating that these abilities are conserved among aphthoviruses. Neither FMDV nor ERAV L(pro) interfered with phosphorylation of RNA-dependent protein kinase (PKR) or eIF2α, indicating that L(pro) does not affect SG formation by inhibiting the PKR-triggered signaling cascade. Taken together, our data suggest that aphthoviruses actively target scaffolding proteins G3BP1 and G3BP2 and antagonize SG formation to modulate the integrated stress response. IMPORTANCE The picornavirus foot-and-mouth disease virus (FMDV) is a notorious animal pathogen that puts a major economic burden on the global livestock industry. Outbreaks have significant consequences for animal health and product safety. Like many other viruses, FMDV must manipulate antiviral host responses to establish infection. Upon infection, viral double-stranded RNA (dsRNA) is detected, which results in the activation of the RNA-dependent protein kinase (PKR)-mediated stress response, leading to a stop in cellular and viral translation and the formation of stress granules (SG), which are thought to have antiviral properties. Here, we show that FMDV can suppress SG formation via its leader protease (L(pro)). Simultaneously, we observed that L(pro) can cleave the SG scaffolding proteins G3BP1 and G3BP2. Understanding the molecular mechanisms of the antiviral host response evasion strategies of FMDV may help to develop countermeasures to control FMDV infections in the future.",,"['Visser, Linda J.', 'Medina, Gisselle N.', 'Rabouw, Huib H.', 'de Groot, Raoul J.', 'Langereis, Martijn A.', 'de los Santos, Teresa', 'van Kuppeveld, Frank J. M.']",,,,
,PMC,HOPS-dependent endosomal fusion required for efficient cytosolic delivery of therapeutic peptides and small proteins,http://dx.doi.org/10.1073/pnas.1812044116,PMC6329960,,,"Protein therapeutics represent a significant and growing component of the modern pharmacopeia, but their potential to treat human disease is limited because most proteins fail to traffic across biological membranes. Recently, we discovered a class of cell-permeant miniature proteins (CPMPs) containing a precisely defined, penta-arginine (penta-Arg) motif that traffics readily to the cytosol and nucleus of mammalian cells with efficiencies that rival those of hydrocarbon-stapled peptides active in animals and man. Like many cell-penetrating peptides (CPPs), CPMPs enter the endocytic pathway; the difference is that CPMPs containing a penta-Arg motif are released efficiently from endosomes, while other CPPs are not. Here, we seek to understand how CPMPs traffic from endosomes into the cytosol and what factors contribute to the efficiency of endosomal release. First, using two complementary cell-based assays, we exclude endosomal rupture as the primary means of endosomal escape. Next, using an RNA interference screen, fluorescence correlation spectroscopy, and confocal imaging, we identify VPS39—a gene encoding a subunit of the homotypic fusion and protein-sorting (HOPS) complex—as a critical determinant in the trafficking of CPMPs and hydrocarbon-stapled peptides to the cytosol. Although CPMPs neither inhibit nor activate HOPS function, HOPS activity is essential to efficiently deliver CPMPs to the cytosol. CPMPs localize within the lumen of Rab7(+) and Lamp1(+) endosomes and their transport requires HOPS activity. Overall, our results identify Lamp1(+) late endosomes and lysosomes as portals for passing proteins into the cytosol and suggest that this environment is prerequisite for endosomal escape.",,"['Steinauer, Angela', 'LaRochelle, Jonathan R.', 'Knox, Susan L.', 'Wissner, Rebecca F.', 'Berry, Samuel', 'Schepartz, Alanna']",,,,
,PMC,PCR Detection of Respiratory Pathogens in Asymptomatic and Symptomatic Adults,http://dx.doi.org/10.1128/JCM.00716-18,PMC6322459,,,"The frequency of viral respiratory pathogens in asymptomatic subjects is poorly defined. The aim of this study was to explore the prevalence of respiratory pathogens in the upper airways of asymptomatic adults, compared with a reference population of symptomatic patients sampled in the same centers during the same period. Nasopharyngeal (NP) swab samples were prospectively collected from adults with and without ongoing symptoms of respiratory tract infection (RTI) during 12 consecutive months, in primary care centers and hospital emergency departments, and analyzed for respiratory pathogens by a PCR panel detecting 16 viruses and four bacteria. Altogether, 444 asymptomatic and 75 symptomatic subjects completed sampling and follow-up (FU) at day 7. In the asymptomatic subjects, the detection rate of viruses was low (4.3%), and the most common virus detected was rhinovirus (3.2%). Streptococcus pneumoniae was found in 5.6% of the asymptomatic subjects and Haemophilus influenzae in 1.4%. The only factor independently associated with low viral detection rate in asymptomatic subjects was age ≥65 years (P = 0.04). An increased detection rate of bacteria was seen in asymptomatic subjects who were currently smoking (P < 0.01) and who had any chronic condition (P < 0.01). We conclude that detection of respiratory viruses in asymptomatic adults is uncommon, suggesting that a positive PCR result from a symptomatic patient likely is relevant for ongoing respiratory symptoms. Age influences the likelihood of virus detection among asymptomatic adults, and smoking and comorbidities may increase the prevalence of bacterial pathogens in the upper airways.",,"['Sundell, Nicklas', 'Andersson, Lars-Magnus', 'Brittain-Long, Robin', 'Sundvall, Pär-Daniel', 'Alsiö, Åsa', 'Lindh, Magnus', 'Gustavsson, Lars', 'Westin, Johan']",,,,
,PMC,Interpretation and clinical practice of regulation for prevention and control of healthcare associated infection in outpatient and emergency department in healthcare facilities,http://dx.doi.org/10.21037/atm.2018.12.05,PMC6351364,,,"Healthcare associated infection (HAI) control and prevention is the important component of medical safety. Healthcare workers (HCWs) are the core forces for implementing good HAI control and prevention. Several cases of outbreaks occurred in outpatient and emergency department (OED) strengthened the importance of infection control and prevention. Recently, the “Regulation for prevention and control of HAI in outpatient and emergency department in healthcare facilities” was released by National health Commission of the People’s Republic of China on May 10, 2018 and was going to implement on Nov 1, 2018. This regulation stipulates basic infection prevention requirements for safe care in OED of healthcare facilities. In this article, we would provide the interpretation and clinical practice of regulation for prevention and control of HAI in outpatient and emergency department in healthcare facilities and give a summary introduction.",,"['Chen, Wen-Sen', 'Qiao, Fu', 'Yang, Yue', 'Gao, Xiao-Dong', 'Li, Zhan-Jie', 'Zhang, Yong-Xiang', 'Zhang, Wei-Hong', 'Fu, Qiang', 'Liu, Yun']",,,,
,PMC,Development and biochemical and immunological characterization of early passage and immortalized bovine intestinal epithelial cell lines from the ileum of a young calf,http://dx.doi.org/10.1007/s10616-018-0272-y,PMC6368510,,,"The intestinal epithelium is a major site of interaction with pathogens. In bovine intestinal epithelial cells (BIECs), Toll-like receptors (TLRs) play an important role in innate immune responses against enteric pathogens. This study is aimed at establishing a stable bovine intestinal epithelial cell line that can be maintained by a continuous passage so that studies on innate immune responses against various enteric pathogens can be performed. The main goal was to establish pure cultures of primary and immortalized bovine intestinal epithelial cells from the ileum and then characterize them biochemically and immunologically. Mixed epithelial and fibroblast bovine ileal intestinal cultures were first established from a 2-day old calf. Limiting dilution method was used to obtain a clone of epithelial cells which was characterized using immunocytochemistry (ICC). The selected clone BIEC-c4 was cytokeratin positive and expressed low levels of vimentin, confirming the epithelial cell phenotype. Early passage BIEC-c4 cells were transfected with either simian virus 40 (SV40) large T antigen or human telomerase reverse transcriptase (hTERT), or human papillomavirus (HPV) type 16E6/E7 genes to establish three immortalized BIEC cell lines. The expression of SV40, hTERT and HPV E6/E7 genes in immortalized BIECs was confirmed by a polymerase chain reaction (PCR). Immunocytochemistry and immunofluorescence assays also confirmed the expression of SV40, hTERT and HPV E6 proteins. The immortalized BIECs were cytokeratin positive and all except HPV-BIECs expressed low levels of vimentin. A growth kinetics study indicated that there were no significant differences in the doubling time of immortalized BIECs as compared to early passage BIEC-c4 cells. All four BIEC types expressed TLR 1-10 genes, with TLR 3 and 4 showing higher expression across all cell types. These newly established early passage and immortalized BIEC cell lines should serve as a good model for studying infectivity, pathogenesis and innate immune responses against enteric pathogens.",,"['Katwal, Pratik', 'Thomas, Milton', 'Uprety, Tirth', 'Hildreth, Michael B.', 'Kaushik, Radhey S.']",,,,
,PMC,Genotyping of avian infectious bronchitis virus in Afghanistan (2016-2017): the first report,,PMC6509913,,,"BACKGROUND: Avian infectious bronchitis (IB) is a highly contagious viral disease which affects the poultry industry. The virus exists in a wide variety of genotypes, and phylogenetic analysis has been used to classify infectious bronchitis virus (IBV) strains. AIMS: The object of the study is a molecular characterization of circulating IBV in Afghanistan as a first study. METHODS: The tracheal tissue specimens from 100 different commercial broiler flocks with respiratory distress in Afghanistan were collected during 2016-2017. After real-time reverse transcriptase-polymerase chain reaction (RRT-PCR), IBV-positive samples were further characterized. A 390 bp hypervariable spike glycoprotein gene segment was amplified using Nested PCR, sequenced, and analyzed. RESULTS: The results of real-time RT-PCR showed that 45/100 of the mentioned flocks were IBV positive. Phylogenetic analysis of all positive samples revealed that IBV strains were clustered into two distinct genotypes: LX4 (GI-19) (9/45) and IS-1494 like (GI-23) (34/45). Also, 2 of the 45 samples remained uncharacterized. CONCLUSION: It is the first study focusing on the molecular epidemiology of IBV in Afghanistan, extending our understanding of IB in the region. These results showed the high rate of IB infection in Afghanistan broiler farms and confirm the continuing monitoring of IBVs to modify the vaccination program.",,"['Sadri, N.', 'Ghalyanchilangeroudi, A.', 'Fallah Mehrabadi, M. H.', 'Hosseini, H.', 'Shayeganmehr, A.', 'Sediqian, M. S.', 'Jabbarifakhr, M.', 'Hamdan, A. M.', 'Mousavi, F. S.']",,,,
,PMC,"Comparison of Isoflurane, Ketamine–Dexmedetomidine, and Ketamine–Xylazine for General Anesthesia during Oral Procedures in Rice Rats (Oryzomys palustris)",http://dx.doi.org/10.30802/AALAS-JAALAS-18-000032,PMC6351055,,,"Rice rats (Oryzomys palustris) are an unconventional laboratory species that has been used to study photoperiodicity, periodontitis, and osteonecrosis of the jaw. Interventional procedures that require anesthesia, including oral procedures, are sometimes necessary in preclinical settings. The use of anesthetics including isoflurane and ketamine combined with α2-adrenoreceptor agonists, such as dexmedetomidine and xylazine, is well-established for laboratory rodents. However, their effects have been studied only modestly in rice rats. The aims of this study were to 1) determine the safety and consistency of 3 common anesthetic modalities in rice rats; 2) compare the physiologic and clinical responses to these anesthetics, and 3) verify the effectiveness of the most successful modality by testing it during an oral procedure (tooth extraction). Isoflurane, intraperitoneal ketamine–dexmedetomidine, and intraperitoneal ketamine–xylazine were evaluated by using a crossover design, in which each rat received all of the anesthetics. Compared with ketamine–dexmedetomidine and ketamine–xylazine, isoflurane inhalation through a nose cone produced more rapid induction, entry to a surgical plane of anesthesia, and initial recovery. In addition, isoflurane produced optimal anesthesia throughout the procedure for most rats. Unlike ketamine–dexmedetomidine and ketamine–xylazine, isoflurane did not alter rectal temperature, SpO(2), or respiratory rate during the surgical tolerance period, whereas ketamine–dexmedetomidine and ketamine–xylazine decreased rectal temperature during the last stage of anesthesia and induced cardiorespiratory depression. Furthermore, 2 rats experienced negative outcomes warranting euthanasia: one after receiving ketamine–dexmedetomidine, and the other after ketamine–xylazine anesthesia. In conclusion, isoflurane was the most reliable and effective anesthetic in rice rats and maintained a surgical depth of anesthesia for as long as 30 min, thus supporting successful tooth extractions.",,"['Jiron, Jessica M', 'Calle, Jorge L Mendieta', 'Castillo, Evelyn J', 'Abraham, Abel M', 'Messer, Jonathan G', 'Malphurs, Wendi L', 'Malinowski, Carolyn', 'Grove, Kristina', 'Reznikov, Leah R', 'Zubcevic, Jasenka', 'Aguirre, J Ignacio']",,,,
,PMC,Wellbeing of Alcohol-preferring Rats Euthanized with Carbon Dioxide at Very Low and Low Volume Displacement Rates,http://dx.doi.org/10.30802/AALAS-JAALAS-18-000004,PMC6351044,,,"The 2013 AVMA Guidelines on Euthanasia recommend the use of very-low or low flow rates of 100% carbon dioxide to euthanize small rodents. Although inhalation of high concentrations of carbon dioxide are generally recognized as painful in humans, whether the use of these low-flow methods of euthanasia increase potential distress for rats is unclear. This study compared physiologic and behavioral markers of animal wellbeing for rats euthanized by using 10% volume displacement per minute (VD/min), 30% VD/min, and 70% VD/min of 100% carbon dioxide. Rats were recorded during euthanasia for subsequent behavioral scoring, and blood samples were taken after euthanasia for assessment of blood glucose and serum corticosterone levels. In this study, rats euthanized with 10% or 30% VD/min of 100% carbon dioxide demonstrated increases in various behaviors, such as rearing and standing, concurrent with increases in serum corticosterone. Rats euthanized with 70% VD/min of 100% carbon dioxide did not exhibit these changes. The results suggest that a euthanasia method of 70% VD/min of 100% carbon dioxide may minimize potential pain and distress and thus be more humane for rats, as compared with very-low– and low-flow methods of carbon dioxide euthanasia.",,"Hickman, Debra L",,,,
,PMC,WACEM 2018 Abstracts,http://dx.doi.org/10.4103/JETS.JETS_1_19,PMC6496987,,CC BY-NC-SA,"The 4(th) Annual World Academic Congress of Emergency Medicine was held in October 2018 in Doha, Qatar. The conference was organized by Trauma Surgeons, Emergency Physicians and Research Team from Qatar. WACEM 2018 was very engaging and informative congress which involved debates, discussion, lectures. competitions and many symposiums. Over 100 International Academic Leaders spoke on cutting-edge research at this congress. The following were the abstracts that were presented at WACEM 2018. There were awards for best papers. A dedicated scientific team worked on selecting and reviewing as well as judging the abstracts.",2019 Jan-Mar,,J Emerg Trauma Shock,,,
,PMC,An interesting case of acute disseminated encephalomyelitis following E. coli infection,http://dx.doi.org/10.4103/jfmpc.jfmpc_402_18,PMC6396596,30911524,CC BY-NC-SA,"Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory demyelinating disease of central nervous system (CNS), characterized by multifocal white matter involvement with neurological deficits and accompanied by encephalopathy. ADEM is thought to be caused by autoimmune etiology. CNS autoantigens are produced by molecular mimicry triggered by an environmental stimulus, mostly infection (viral/bacterial) or post vaccination, in genetically susceptible individuals. ADEM is sometimes referred to as post/para-infectious or post-immunization ADEM. ADEM is characterized by multifocal neurological signs and occasionally it rapidly progresses to coma. Magnetic resonance imaging (MRI) is used to confirm the diagnosis. The treatment is based on intravenous high-dose methylprednisolone, which usually leads to a rapid improvement. Recently, the use of intravenous immunoglobulins and plasma exchange (PLEX) has also been suggested. We report a case of a 6-year-old girl who was admitted for urinary tract infection but developed neurological complications which was treated successfully.",2019 Jan,"['Balamurugesan, Kandan', 'Ponprabha, Rajangam', 'Davis, Prem']",J Family Med Prim Care,,,
,PMC,Viral RNA structure-based strategies to manipulate translation,http://dx.doi.org/10.1038/s41579-018-0117-x,PMC6452865,,,"Viruses are obligate cellular parasites that must co-opt the cellular translation machinery. Eukaryote-infecting viruses have evolved a variety of ways to manipulate the cellular translation apparatus, in many cases using elegant RNA-centered strategies. These viral RNAs can alter or control every phase of the protein-making process, are very diverse in terms of target, mechanism, and the RNA structural characteristics, and are found in a wide range of viruses. In addition, as cells often attempt to limit infection by inhibiting translation, some of these viral RNAs act to overcome the cell’s antiviral response or even take advantage of it to further viral infection. Here, we present important illustrative examples of viral RNA-based strategies to exploit the translation machinery. We briefly describe what is understood of the structure and mechanism of diverse RNA elements, the advantages conferred to the virus, and some of the key unknowns that provide motivation for further exploration.",,"['Jaafar, Zane A.', 'Kieft, Jeffrey S.']",,,,
,PMC,A Balancing Act: MDA5 in Antiviral Immunity and Autoinflammation,http://dx.doi.org/10.1016/j.tim.2018.08.007,PMC6319154,30201512,CC BY,"Induction of interferons during viral infection is mediated by cellular proteins that recognise viral nucleic acids. MDA5 is one such sensor of virus presence and is activated by RNA. MDA5 is required for immunity against several classes of viruses, including picornaviruses. Recent work showed that mutations in the IFIH1 gene, encoding MDA5, lead to interferon-driven autoinflammatory diseases. Together with observations made in cancer cells, this suggests that MDA5 detects cellular RNAs in addition to viral RNAs. It is therefore important to understand the properties of the RNAs which activate MDA5. New data indicate that RNA length and secondary structure are features sensed by MDA5. We review these developments and discuss how MDA5 strikes a balance between antiviral immunity and autoinflammation.",2019 Jan,"['Dias Junior, Antonio Gregorio', 'Sampaio, Natalia G.', 'Rehwinkel, Jan']",Trends Microbiol,,,
,PMC,Analysis of research intensity on infectious disease by disease burden reveals which infectious diseases are neglected by researchers,http://dx.doi.org/10.1073/pnas.1814484116,PMC6329976,,,"Infectious diseases are associated with considerable morbidity and mortality worldwide. Although human, financial, substantial, and time resources are limited, it is unknown whether such resources are used effectively in research to manage diseases. The correlation between the disability-adjusted life years to represent disease burden and number of publications as a surrogate for research activity was investigated to measure burden-adjusted research intensity for 52 infectious diseases at global and country levels. There was significantly low research intensity for paratyphoid fever and high intensity for influenza, HIV/acquired immunodeficiency syndrome, hepatitis C, and tuberculosis considering their disease burden. We identified the infectious diseases that have received the most attention from researchers and those that have been relatively disregarded. Interestingly, not all so-called neglected tropical diseases were subject to low burden-adjusted research intensity. Analysis of the intensity of infectious disease research at a country level revealed characteristic patterns. These findings provided a basis for further discussion of the more appropriate allocation of resources for research into infectious diseases.",,"Furuse, Yuki",,,,
,PMC,"A reverse-transcription/RNase H based protocol for depletion of mosquito ribosomal RNA facilitates viral intrahost evolution analysis, transcriptomics and pathogen discovery",http://dx.doi.org/10.1016/j.virol.2018.12.020,PMC6934164,,,"Identifying novel viruses or assessing viral variation by NGS requires high sequencing coverage. More than 90% of total RNA is ribosomal (rRNA), making variant calling, virus discovery or transcriptomic profiling difficult. Current methods to increase informative reads suffer from drawbacks, either they cannot be used for some viruses, are optimized for a single species, or introduce bias. We describe a two-part approach combining reverse-transcription to create RNA/DNA hybrids which are then degraded with RNaseH/DNase sequentially that works for three medically relevant mosquito genera; Aedes, Anopheles, and Culex. We demonstrate depletion of rRNA from different samples, including whole mosquitoes and midgut contents from FTA cards. We describe novel insect-specific virus genomes from field collected mosquitoes. The protocol requires only common laboratory reagents and small oligonucleotides specific to rRNA. This approach can be adapted for other organisms, aiding virus diversity analyses, virus discovery and transcriptomics in both laboratory and field samples.",,"['Fauver, Joseph R.', 'Akter, Shamima', 'Morales, Aldo Ivan Ortega', 'Black, William C.', 'Rodriguez, Americo D.', 'Stenglein, Mark D.', 'Ebel, Gregory D.', 'Weger-Lucarelli, James']",,,,
,PMC,The effect of a porcine reproductive and respiratory syndrome outbreak on genetic parameters and reaction norms for reproductive performance in pigs,http://dx.doi.org/10.1093/jas/sky485,PMC6396237,,,"The objective of this study was to estimate genetic parameters of antibody response and reproductive traits after exposure to porcine reproductive and respiratory syndrome virus. Blood samples were taken approximately 60 d after the outbreak. Antibody levels were quantified as the sample-to-positive ratio (S/P ratio) using a fluorescent microsphere assay. Reproductive traits included total number born (TNB), number born alive (NBA), number stillborn (NSB), number mummified (NBM), and number born dead (NBD). Mortality traits were log transformed for genetic analyses. Data were split into prior, during, and after the disease outbreak phases using visual appraisal of the estimates of farm-year-week effects for each reproductive trait. For NBA, data from all phases were combined into a reaction norm analysis with regression on estimates of farm-year-week effects for NBA. Heritability for S/P ratio was estimated at 0.17 ± 0.05. Heritability estimates for reproduction traits were all low and were lower during the outbreak for NBA but greater for mortality traits. TNB was not greatly affected during the outbreak, as many sows that farrowed during the outbreak were mated prior to the outbreak. Heritability for TNB decreased from 0.13 (prior) to 0.08 (after). Genetic correlation estimates between prior to and during the outbreak were high for TNB (0.86 ± 0.23) and NBA (0.98 ± 0.38) but lower for mortality traits: 0.65 ± 0.43, −0.42 ± 0.55, and 0.29 ± 1.39 for LNSB, LNBM, and LNBD, respectively. TNB prior to and after the outbreak had a lower genetic correlation (0.32 ± 0.33). In general, genetic correlation estimates of S/P ratio with reproductive performance during the outbreak were below 0.20 in absolute value, except for LNSB (−0.73 ± 0.29). Based on the reaction norm model, estimates of genetic correlations between the intercept and slope terms ranged from 0.24 ± 0.50 to 0.54 ± 0.35 depending on the parameterization used, indicating that selection for the intercept may result in indirect selection for steeper slopes, and thus, less resilient animals. In general, estimates of genetic correlations between farm-year-week effect classes based on the reaction norm model resembled estimates of genetic correlations from the multivariate analysis. Overall, compared to previous studies, antibody S/P ratios showed a lower heritability (0.17 ± 0.05) and low genetic correlations with reproductive performance during a porcine reproductive and respiratory syndrome outbreak, except for the LNSB.",,"['Putz, Austin M', 'Schwab, Clint R', 'Sewell, Alysta D', 'Holtkamp, Derald J', 'Zimmerman, Jeffery J', 'Baker, Kimberlee', 'Serão, Nick V L', 'Dekkers, Jack C M']",,,,
,PMC,Respiratory Viral Infection: An Underappreciated Cause of Acute Febrile Illness Admissions in Southern Sri Lanka,http://dx.doi.org/10.4269/ajtmh.18-0699,PMC6402941,,,"The contribution of respiratory viruses to acute febrile illness (AFI) burden is poorly characterized. We describe the prevalence, seasonality, and clinical features of respiratory viral infection among AFI admissions in Sri Lanka. We enrolled AFI patients ≥ 1 year of age admitted to a tertiary care hospital in southern Sri Lanka, June 2012–October 2014. We collected epidemiologic/clinical data and a nasal or nasopharyngeal sample that was tested using polymerase chain reaction (Luminex NxTAG, Austin, TX). We determined associations between weather data and respiratory viral activity using the Spearman correlation and assessed respiratory virus seasonality using a Program for Appropriate Technology definition. Bivariable and multivariable regression analyses were conducted to identify features associated with respiratory virus detection. Among 964 patients, median age was 26.2 years (interquartile range 14.6–39.9) and 646 (67.0%) were male. One-fifth (203, 21.1%) had respiratory virus detected: 13.9% influenza, 1.4% human enterovirus/rhinovirus, 1.4% parainfluenza virus, 1.1% respiratory syncytial virus, and 1.1% human metapneumovirus. Patients with respiratory virus identified were younger (median 9.8 versus 27.7 years, P < 0.001) and more likely to have respiratory signs and symptoms. Influenza A and respiratory viral activity peaked in February–June each year. Maximum daily temperature was associated with influenza and respiratory viral activity (P = 0.03 each). Patients with respiratory virus were as likely as others to be prescribed antibiotics (55.2% versus 52.6%, P = 0.51), and none reported prior influenza vaccination. Respiratory viral infection was a common cause of AFI. Improved access to vaccines and respiratory diagnostics may help reduce disease burden and inappropriate antibiotic use.",,"['Tillekeratne, L. Gayani', 'Bodinayake, Champica K.', 'Simmons, Ryan', 'Nagahawatte, Ajith', 'Devasiri, Vasantha', 'Kodikara Arachchi, Wasantha', 'Nicholson, Bradly P.', 'Park, Lawrence P.', 'Vanderburg, Sky', 'Kurukulasooriya, Ruvini', 'De Silva, Aruna Dharshan', 'Østybe, Truls', 'Reller, Megan E.', 'Woods, Christopher W.']",,,,
,PMC,On the Centenary of the Spanish Flu: Being Prepared for the Next Pandemic,http://dx.doi.org/10.1007/s12250-018-0079-1,PMC6335225,,,,,"['Liu, William J.', 'Bi, Yuhai', 'Wang, Dayan', 'Gao, George F.']",,,,
,PMC,Mechanisms of lymphatic system‐specific viral replication and its potential role in autoimmune disease,http://dx.doi.org/10.1111/cei.13241,PMC6300653,,,"Viral infections can be fatal because of the direct cytopathic effects of the virus or the induction of a strong, uncontrolled inflammatory response. Virus and host intrinsic characteristics strongly modulate the outcome of viral infections. Recently we determined the circumstances under which enhanced replication of virus within the lymphoid tissue is beneficial for the outcome of a disease. This enforced viral replication promotes anti‐viral immune activation and, counterintuitively, accelerates virus control. In this review we summarize the mechanisms that contribute to enforced viral replication. Antigen‐presenting cells and CD169(+) macrophages exhibit enforced viral replication after infection with the model viruses lymphocytic choriomeningitis virus (LCMV) and vesicular stomatitis virus (VSV). Ubiquitin‐specific peptidase 18 (Usp18), an endogenous type I interferon blocker in CD169(+) macrophages, has been identified as a proviral gene, as are B cell activating factor (BAFF) and carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1). Lymphotoxins (LT) strongly enhance viral replication in the spleen and lymph nodes. All these factors modulate splenic architecture and thereby promote the development of CD169(+) macrophages. Tumor necrosis factor alpha (TNF‐α) and nuclear factor kappa‐light‐chain‐enhancer of activated B cell signaling (NF‐κB) have been found to promote the survival of infected CD169(+) macrophages, thereby similarly promoting enforced viral replication. Association of autoimmune disease with infections is evident from (1) autoimmune phenomena described during a chronic virus infection; (2) onset of autoimmune disease simultaneous to viral infections; and (3) experimental evidence. Involvement of virus infection during onset of type I diabetes is strongly evident. Epstein–Bar virus (EBV) infection was discussed to be involved in the pathogenesis of systemic lupus erythematosus. In conclusion, several mechanisms promote viral replication in secondary lymphatic organs. Identifying such factors in humans is a challenge for future studies.",,"['Friedrich, S.‐K.', 'Lang, P. A.', 'Friebus‐Kardash, J.', 'Duhan, V.', 'Bezgovsek, J.', 'Lang, K. S.']",,,,
,PMC,"Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity",http://dx.doi.org/10.1128/MMBR.00038-18,PMC6383445,,,"The literature review presented here details recent research involving members of the poly(ADP-ribose) polymerase (PARP) family of proteins. Among the 17 recognized members of the family, the human enzyme PARP1 is the most extensively studied, resulting in a number of known biological and metabolic roles. This review is focused on the roles played by PARP enzymes in host-pathogen interactions and in diseases with an associated inflammatory response. In mammalian cells, several PARPs have specific roles in the antiviral response; this is perhaps best illustrated by PARP13, also termed the zinc finger antiviral protein (ZAP). Plant stress responses and immunity are also regulated by poly(ADP-ribosyl)ation. PARPs promote inflammatory responses by stimulating proinflammatory signal transduction pathways that lead to the expression of cytokines and cell adhesion molecules. Hence, PARP inhibitors show promise in the treatment of inflammatory disorders and conditions with an inflammatory component, such as diabetes, arthritis, and stroke. These functions are correlated with the biophysical characteristics of PARP family enzymes. This work is important in providing a comprehensive understanding of the molecular basis of pathogenesis and host responses, as well as in the identification of inhibitors. This is important because the identification of inhibitors has been shown to be effective in arresting the progression of disease.",,"['Brady, Pamlea N.', 'Goel, Anupam', 'Johnson, Margaret A.']",,,,
,PMC,Obstetric and Neonatal Outcomes of Pregnant Indian Pilgrims: A three-year experience at the Indian Hajj Medical Mission,http://dx.doi.org/10.18295/squmj.2018.18.03.015,PMC6307628,,,"OBJECTIVES: The Hajj, an annual mass gathering of Muslim pilgrims, is known for its high morbidity and mortality rates. However, pregnant women sometimes participate in this pilgrimage, despite guidelines that discourage such an undertaking due to potential fetomaternal complications. This study aimed to evaluate fetomaternal outcomes among pregnant Indian Hajj pilgrims. METHODS: This prospective cross-sectional study was conducted at two Indian Hajj Medical Mission (IHMM)-affiliated secondary care hospitals in Saudi Arabia during the Hajj periods of August–October 2015 and 2016 and July–September 2017. All female Indian pilgrims of reproductive age who underwent pregnancy screening at secondary care IHMM hospitals during this period were included in the study. Definitive obstetric care was provided at the Makkah Maternity & Child Hospital. Data regarding the pilgrims’ obstetric characteristics, antenatal complications, management and fetomaternal outcomes were evaluated. RESULTS: A total of 114 pregnant Indian pilgrims were identified during the study period. The most common antenatal complications were respiratory tract infections (51.75%), followed by iron deficiency anaemia (17.54%), hyperemesis gravidarum (14.04%), hypothyroidism (9.65%) and gestational diabetes mellitus (5.26%). There were 20 vaginal deliveries (17.54%), two Caesarean sections (1.75%) and 32 abortions (28.07%). The cumulative three-year birth rate was 24.60 per 1,000 females. CONCLUSION: During Hajj, pregnant pilgrims have a high risk of abortion, respiratory tract infections and various antenatal, perinatal and neonatal complications which may go unreported or untreated. Women should therefore be educated regarding the risk of adverse fetomaternal outcomes which may occur while undertaking a Hajj pilgrimage during pregnancy.",,"['Khan, Shazia', 'Khan, Inam D.']",,,,
,PMC,Gonadal pathogenicity of an infectious bronchitis virus strain from the Massachusetts genotype,http://dx.doi.org/10.1007/s42770-018-0007-4,PMC6863202,,,"An outbreak of infectious bronchitis caused by the IBVPR03 strain of the Massachusetts genotype affected H-120 vaccinated laying hens in South Brazil. We investigated the cross protection of the vaccine by assessing the traqueal ciliostasis, virus recovery, and histopathological changes typically observed in the respiratory tract. Although the IBVPR03 strain is S1-genotyped as Massachusetts with a high genomic similarity to the H-120 vaccine strains, surprisingly, we found no tropism or pathogenicity to the trachea in birds infected with this strain. On the other hand, we observed ovarian and testicle lesions. Here, we show that, despite belonging in the Massachusetts genotype, the IBVPR03 pathotype differs from the expected respiratory pattern, causing instead marked histopathological changes in the gonads, so far not associated with this group.",,"['Pereira, Nicole Assis', 'Alessi, Antônio Carlos', 'Montassier, Hélio José', 'Pereira, Ricardo José Garcia', 'Taniwaki, Sueli Akemi', 'Botosso, Viviane Fongaro', 'Rui, Bruno Rogério', 'Richtzenhain, Leonardo José']",,,,
,PMC,Primary Human Neutrophils Exhibit a Unique HIV-Directed Antibody-Dependent Phagocytosis Profile,http://dx.doi.org/10.1159/000494371,PMC6402977,,,"The only clinical HIV vaccine trial to demonstrate efficacy, RV144, correlated protection with the antibodies (Abs) mediating function via the “constant” immunoglobulin region, the crystallizable fragment (Fc). These data have supported a focus on the induction of Abs by vaccines that trigger antiviral activities by relevant leukocytes via Fc receptors (FcRs). Neutrophils are phagocytes that comprise > 50% of leukocytes and display unique FcRs. We sought to compare the Ab-dependent cellular phagocytosis (ADCP) activity of human neutrophils to the commonly assayed THP-1 cell line. HIV-specific Abs were employed to elicit ADCP of beads coated with HIV envelope protein. Overall, trends were noted among neutrophil donors and the ADCP profile was different from that of THP-1 cells. mAb ELISA titers correlated with ADCP by THP-1 cells but not neutrophils. Monoclonal (m)Abs were also tested with primary monocytes. Donor-to-donor variation was high, and hindered the analysis of this dataset, but it was, in itself, an important finding. This study illustrates the concept that the assessment of FcR-mediated Ab activity with a frequently used cell line such as THP-1 is not necessarily indicative of relevant Ab functionality in vivo, and this calls for in-depth study of the properties of the HIV antibodies best-suited to eliciting antiviral activities by primary cells.",,"['Powell, Rebecca L.R.', 'Fox, Alisa', 'Itri, Vincenza', 'Zolla-Pazner, Susan']",,,,
,PMC,High Throughput and Computational Repurposing for Neglected Diseases,http://dx.doi.org/10.1007/s11095-018-2558-3,PMC6792295,,,"PURPOSE: Neglected tropical diseases (NTDs) represent are a heterogeneous group of communicable diseases that are found within the poorest populations of the world. There are 23 NTDs that have been prioritized by the World Health Organization, which are endemic in 149 countries and affect more than 1.4 billion people, costing these developing economies billions of dollars annually. The NTDs result from four different causative pathogens: protozoa, bacteria, helminth and virus. The majority of the diseases lack effective treatments. Therefore, new therapeutics for NTDs are desperately needed. METHODS: We describe various high throughput screening and computational approaches that have been performed in recent years. We have collated the molecules identified in these studies and calculated molecular properties. RESULTS: Numerous global repurposing efforts have yielded some promising compounds for various neglected tropical diseases. These compounds when analyzed as one would expect appear drug-like. Several large datasets are also now in the public domain and this enables machine learning models to be constructed that then facilitate the discovery of new molecules for these pathogens. CONCLUSIONS: In the space of a few years many groups have either performed experimental or computational repurposing high throughput screens against neglected diseases. These have identified compounds which in many cases are already approved drugs. Such approaches perhaps offer a more efficient way to develop treatments which are generally not a focus for global pharmaceutical companies because of the economics or the lack of a viable market. Other diseases could perhaps benefit from these repurposing approaches.",,"['Hernandez, Helen W.', 'Soeung, Melinda', 'Zorn, Kimberley M.', 'Ashoura, Norah', 'Mottin, Melina', 'Andrade, Carolina Horta', 'Caffrey, Conor R.', 'de Siqueira-Neto, Jair Lage', 'Ekins, Sean']",,,,
,PMC,Technologies to address antimicrobial resistance,http://dx.doi.org/10.1073/pnas.1717160115,PMC6304975,,,"Bacterial infections have been traditionally controlled by antibiotics and vaccines, and these approaches have greatly improved health and longevity. However, multiple stakeholders are declaring that the lack of new interventions is putting our ability to prevent and treat bacterial infections at risk. Vaccine and antibiotic approaches still have the potential to address this threat. Innovative vaccine technologies, such as reverse vaccinology, novel adjuvants, and rationally designed bacterial outer membrane vesicles, together with progress in polysaccharide conjugation and antigen design, have the potential to boost the development of vaccines targeting several classes of multidrug-resistant bacteria. Furthermore, new approaches to deliver small-molecule antibacterials into bacteria, such as hijacking active uptake pathways and potentiator approaches, along with a focus on alternative modalities, such as targeting host factors, blocking bacterial virulence factors, monoclonal antibodies, and microbiome interventions, all have potential. Both vaccines and antibacterial approaches are needed to tackle the global challenge of antimicrobial resistance (AMR), and both areas have the underpinning science to address this need. However, a concerted research agenda and rethinking of the value society puts on interventions that save lives, by preventing or treating life-threatening bacterial infections, are needed to bring these ideas to fruition.",,"['Baker, Stephen J.', 'Payne, David J.', 'Rappuoli, Rino', 'De Gregorio, Ennio']",,,,
,PMC,The GenMark ePlex(®): another weapon in the syndromic arsenal for infection diagnosis,http://dx.doi.org/10.2217/fmb-2018-0258,PMC6439521,,,"As one of the most recent additions to the syndromic testing landscape, the ePlex(®) platform by GenMark Diagnostics is a system that combines the manufacturer's signature electrochemical detection technology with updated microfluidics, providing a new option for multiplex testing that is both rapid and requires minimal hands-on steps. In this review, we detail the ePlex platform and its current/future syndromic panels, with a particular focus on the respiratory pathogen panel – the platform's first assay to undergo clinical trials and receive regulatory approval in the USA. By keeping informed of these ever-expanding laboratory options, clinicians and microbiologists can stay positioned at the forefront of infectious disease diagnosis.",,"['Schmitz, Jonathan E', 'Tang, Yi-Wei']",,,,
,PMC,Emerging technologies for the detection of viral infections,http://dx.doi.org/10.2217/fvl-2018-0145,PMC6956246,,,"Viruses represent one of the major environmental agents that cause human illness and disease. However, the ability to diagnose viral infections is limited by detection capability and scope. Here we describe several emerging technologies that provide rapid and/or high-quality viral diagnostic information. Two technologies, novel CRISPR-based diagnostics and a portable DNA sequencing instrument, are uniquely suited to increase the number of viral agents analyzed, even in point of care settings. We also discuss a phage-based method for generating comprehensive viral profiles of previous exposure/infection and a fluid-phase immunoassay that yields highly quantitative viral antibody analyses. Future applications of these approaches will accelerate on-site clinical diagnosis of viral infections and provide insights into the role viruses play in complex diseases.",,"['Burbelo, Peter D.', 'Iadarola, Michael J.', 'Chaturvedi, Adrija']",,,,
,PMC,Questioning Estimates of Natural Pandemic Risk,http://dx.doi.org/10.1089/hs.2018.0039,PMC6306648,,,"The central argument in this article is that the probability of very large natural pandemics is more uncertain than either previous analyses or the historical record suggest. In public health and health security analyses, global catastrophic biological risks (GCBRs) have the potential to cause “sudden, extraordinary, widespread disaster,” with “tens to hundreds of millions of fatalities.” Recent analyses focusing on extreme events presume that the most extreme natural events are less likely than artificial sources of GCBRs and should receive proportionately less attention. These earlier analyses relied on an informal Bayesian analysis of naturally occurring GCBRs in the historical record and conclude that the near absence of such events demonstrates that they are rare. This ignores key uncertainties about both selection biases inherent in historical data and underlying causes of the nonstationary risk. The uncertainty is addressed here by first reconsidering the assumptions in earlier Bayesian analyses, then outlining a more complete analysis accounting for several previously omitted factors. Finally, relationships are suggested between available evidence and the uncertain question at hand, allowing more rigorous future estimates.",,"Manheim, David",,,,
,PMC,Tracking virus outbreaks in the 21st century,http://dx.doi.org/10.1038/s41564-018-0296-2,PMC6345516,,,"Emerging viruses have the potential to impose substantial mortality, morbidity and economic burdens on human populations. Tracking the spread of infectious diseases to assist in their control has traditionally relied on the analysis of case data gathered as the outbreak proceeds. Here, we describe how many of the key questions in infectious disease epidemiology, from the initial detection and characterization of outbreak viruses, to transmission chain tracking and outbreak mapping, can now be much more accurately addressed using recent advances in virus sequencing and phylogenetics. We highlight the utility of this approach with the hypothetical outbreak of an unknown pathogen, ‘Disease X’, suggested by the World Health Organization to be a potential cause of a future major epidemic. We also outline the requirements and challenges, including the need for flexible platforms that generate sequence data in real-time, and for these data to be shared as widely and openly as possible.",,"['Grubaugh, Nathan D', 'Ladner, Jason T', 'Lemey, Philippe', 'Pybus, Oliver G', 'Rambaut, Andrew', 'Holmes, Edward C', 'Andersen, Kristian G']",,,,
,PMC,Spatio-temporal transcriptomic divergence across human and macaque brain development,http://dx.doi.org/10.1126/science.aat8077,PMC6900982,,,"Human nervous system development is an intricate and protracted process that requires precise spatio-temporal transcriptional regulation. Here we generated tissue-level and single-cell transcriptomic data from up to sixteen brain regions covering prenatal and postnatal rhesus macaque development. Integrative analysis with complementary human data revealed that global intra-species (ontogenetic) and inter-species (phylogenetic) regional transcriptomic differences exhibit concerted cup-shaped patterns, with a late fetal-to-infancy (perinatal) convergence. Prenatal neocortical transcriptomic patterns revealed transient topographic gradients, whereas postnatal patterns largely reflected functional hierarchy. Genes exhibiting heterotopic and heterochronic divergence included those transiently enriched in the prenatal prefrontal cortex or linked to autism spectrum disorder and schizophrenia. Our findings shed light on transcriptomic programs underlying the evolution of human brain development and the pathogenesis of neuropsychiatric disorders.",,"['Zhu, Ying', 'Sousa, André M. M.', 'Gao, Tianliuyun', 'Skarica, Mario', 'Li, Mingfeng', 'Santpere, Gabriel', 'Esteller-Cucala, Paula', 'Juan, David', 'Ferrández-Peral, Luis', 'Yang, Mo', 'Miller, Daniel J.', 'Marques-Bonet, Tomas', 'Kawasawa, Yuka Imamura', 'Zhao, Hongyu', 'Sestan, Nenad']",,,,
,PMC,Practical Guidance for Clinical Microbiology Laboratories: Viruses Causing Acute Respiratory Tract Infections,http://dx.doi.org/10.1128/CMR.00042-18,PMC6302358,,,"Respiratory viral infections are associated with a wide range of acute syndromes and infectious disease processes in children and adults worldwide. Many viruses are implicated in these infections, and these viruses are spread largely via respiratory means between humans but also occasionally from animals to humans. This article is an American Society for Microbiology (ASM)-sponsored Practical Guidance for Clinical Microbiology (PGCM) document identifying best practices for diagnosis and characterization of viruses that cause acute respiratory infections and replaces the most recent prior version of the ASM-sponsored Cumitech 21 document, Laboratory Diagnosis of Viral Respiratory Disease, published in 1986. The scope of the original document was quite broad, with an emphasis on clinical diagnosis of a wide variety of infectious agents and laboratory focus on antigen detection and viral culture. The new PGCM document is designed to be used by laboratorians in a wide variety of diagnostic and public health microbiology/virology laboratory settings worldwide. The article provides guidance to a rapidly changing field of diagnostics and outlines the epidemiology and clinical impact of acute respiratory viral infections, including preferred methods of specimen collection and current methods for diagnosis and characterization of viral pathogens causing acute respiratory tract infections. Compared to the case in 1986, molecular techniques are now the preferred diagnostic approaches for the detection of acute respiratory viruses, and they allow for automation, high-throughput workflows, and near-patient testing. These changes require quality assurance programs to prevent laboratory contamination as well as strong preanalytical screening approaches to utilize laboratory resources appropriately. Appropriate guidance from laboratorians to stakeholders will allow for appropriate specimen collection, as well as correct test ordering that will quickly identify highly transmissible emerging pathogens.",,"['Charlton, Carmen L.', 'Babady, Esther', 'Ginocchio, Christine C.', 'Hatchette, Todd F.', 'Jerris, Robert C.', 'Li, Yan', 'Loeffelholz, Mike', 'McCarter, Yvette S.', 'Miller, Melissa B.', 'Novak-Weekley, Susan', 'Schuetz, Audrey N.', 'Tang, Yi-Wei', 'Widen, Ray', 'Drews, Steven J.']",,,,
,PMC,DDX3 Participates in Translational Control of Inflammation Induced by Infections and Injuries,http://dx.doi.org/10.1128/MCB.00285-18,PMC6290373,,,"Recent studies have suggested that DDX3 functions in antiviral innate immunity, but the underlying mechanism remains elusive. We previously identified target mRNAs whose translation is controlled by DDX3. Pathway enrichment analysis of these targets indicated that DDX3 is involved in various infections and inflammation. Using immunoblotting, we confirmed that PACT, STAT1, GNB2, Rac1, TAK1, and p38 mitogen-activated protein kinase (MAPK) proteins are downregulated by DDX3 knockdown in human monocytic THP-1 cells and epithelial HeLa cells. Polysome profiling revealed that DDX3 knockdown reduces the translational efficiency of target mRNAs. We further demonstrated DDX3-mediated translational control of target mRNAs by luciferase reporter assays. To examine the effects of DDX3 knockdown on macrophage migration and phagocytosis, we performed in vitro cell migration assay and flow cytometry analysis of the uptake of green fluorescent protein-expressing Escherichia coli in THP-1 cells. The DDX3 knockdown cells exhibited impaired macrophage migration and phagocytosis. Moreover, we used a human cytokine antibody array to identify the cytokines affected by DDX3 knockdown. Several chemokines were decreased considerably in DDX3 knockdown THP-1 cells after lipopolysaccharide or poly(I·C) stimulation. Lastly, we demonstrated that DDX3 is crucial for the recruitment of phagocytes to the site of inflammation in transgenic zebrafish.",,"['Ku, Yu-Chang', 'Lai, Min-Hua', 'Lo, Chen-Chia', 'Cheng, Yi-Chuan', 'Qiu, Jian-Tai', 'Tarn, Woan-Yuh', 'Lai, Ming-Chih']",,,,
,PMC,Diagnostic Value of Platelet and Leukocyte Counts in the Differential Diagnosis of Fever in the Returning Traveler,http://dx.doi.org/10.4269/ajtmh.18-0736,PMC6367606,,,"Malaria, arbovirus infection and travelers’ diarrhea are among the most common etiologies of fever after a stay in the tropics. Because the initial symptoms of these diseases often overlap, the differential diagnostic remains a challenge. The aim of this study was to establish the effectiveness of platelet and leukocyte counts in the differential diagnosis of fever in the returning traveler. Between 2013 and 2016, patients with a clinical suspicion of malaria, who had thick blood smears performed were retrospectively included. The microbiological etiology of each episode was established based on molecular detection in the case of arbovirus infection, the detection of pathogens in stool samples for diarrhea and other gastrointestinal symptoms and the thick and thin blood smear results for malaria. A total of 1,218 episodes were included. Malaria, arbovirus infection, and diarrhea and other gastrointestinal symptoms caused 102 (8.4%), 68 (5.6%), and 72 (5.9%) episodes, respectively. The median platelet counts in malaria episodes were 89 × 10(9)/L and thrombocytopenia (< 150,000 × 10(9) platelets/L) yielded a 98% negative predictive value to predict malaria. The median leukocyte counts in arbovirus infection episodes were 3.19 × 10(9)/L and leucopenia (< 4 × 10(9) leukocytes/L) yielded a 97.9% negative predictive value to predict arbovirus infections. Platelet and leukocyte counts were not significantly altered in episodes caused by diarrhea and other gastrointestinal symptoms. Initial platelet and leukocyte counts might be useful for the clinical differential diagnosis of fever in the returning traveler. Although these results are insufficient to establish a diagnosis, they should be considered in the initial clinical assessment.",,"['Rubio, Elisa', 'Alejo-Cancho, Izaskun', 'Aylagas, Cristian', 'Camprubí, Daniel', 'Ferré, Roser', 'Albarracín, Ma Rosa', 'Gonzalo, Verónica', 'Barrachina, Josep', 'Álvarez-Martínez, Míriam José', 'Valls, Maria Eugenia', 'Mas, Jordi', 'Vila, Jordi', 'Losada, Irene', 'Martínez, Miguel J.', 'Casals-Pascual, Climent']",,,,
,PMC,"Customs officers in relation to viral infections, tuberculosis, psittacosis and environmental health risk",http://dx.doi.org/10.3892/etm.2018.7077,PMC6327673,,,"Customs Service is a financial authority responsible for controlling the flow of importation and exportation goods in each country and for collecting the relevant taxes. Customs officers are considered as ‘high-demand’ and ‘high-responsibility’ governmental officials, which constitute members of multidisciplinary teams at the local, as well as international level and collaborate with different authorities, including medical officers. Despite limited data in the medical literature, customs officers are considered as a ‘high-risk’ occupational group for infections and environmental health risk. During the severe acute respiratory syndrome (SARS) and influenza A/H1N1 pandemic outbreaks in 2003 and 2009, respectively, customs officers had a fundamental front-line input in the establishment of the recommended at that time border measures. In Belgium in 1994, a psittacosis outbreak occurred in customs officers following their exposure to illegally imported parakeets. During the recent increased immigration proceedings, customs officers have been involved in detaining unauthorized populations for various infectious diseases, such as tuberculosis, varicella and measles. Occupational risk for customs officers also includes noise-induced hearing loss, exposure to diesel engine emission and stored tobacco and occupational stress due to their increased time-schedule and decision-making duties. In this review, we discuss customs officers' occupational risk towards environmental and infectious factors, including viral infections, tuberculosis and psittacosis.",,"['Mamma, Maria', 'Spandidos, Demetrios A.']",,,,
,PMC,Going the Distance: Optimizing RNA-Seq Strategies for Transcriptomic Analysis of Complex Viral Genomes,http://dx.doi.org/10.1128/JVI.01342-18,PMC6288342,,,"Transcriptome profiling has become routine in studies of many biological processes. However, the favored approaches such as short-read Illumina RNA sequencing are giving way to long-read sequencing platforms better suited to interrogating the complex transcriptomes typical of many RNA and DNA viruses. Here, we provide a guide—tailored to molecular virologists—to the ins and outs of viral transcriptome sequencing and discuss the strengths and weaknesses of the major RNA sequencing technologies as tools to analyze the abundance and diversity of the viral transcripts made during infection.",,"['Depledge, Daniel P.', 'Mohr, Ian', 'Wilson, Angus C.']",,,,
,PMC,The evolution of antiviral nucleoside analogues: A review for chemists and non-chemists. Part II: complex modifications to the nucleoside scaffold,http://dx.doi.org/10.1016/j.antiviral.2018.11.016,PMC6349489,,,"This is the second of two invited articles reviewing the development of nucleoside analogue antiviral drugs, written for a target audience of virologists and other non-chemists, as well as chemists who may not be familiar with the field. As with the first paper, rather than providing a chronological account, we have chosen to examine particular examples of structural modifications made to nucleoside analogues that have proven fruitful as various antiviral, anticancer, and other therapeutics. The first review covered the more common, and in most cases, single modifications to the sugar and base moieties of the nucleoside scaffold. This paper focuses on more recent developments, especially nucleoside analogues that contain more than one modification to the nucleoside scaffold. We hope that these two articles will provide an informative historical perspective of some of the successfully designed analogues, as well as many candidate compounds that encountered obstacles.",,"['Yates, Mary K.', 'Seley-Radtke, Katherine L.']",,,,
,PMC,Evaluation on the efficacy and immunogenicity of recombinant DNA plasmids expressing S gene from porcine epidemic diarrhea virus and VP7 gene from porcine rotavirus,http://dx.doi.org/10.1007/s42770-018-0022-5,PMC6863295,,,"Porcine rotavirus (PoRV) and porcine epidemic diarrhea virus (PEDV) usually co-infect pigs in modern large-scale piggery, which both can cause severe diarrhea in newborn piglets and lead to significant economic losses to the pig industry. The VP7 protein is the main coat protein of PoRV, and the S protein is the main structural protein of PEDV, which are capable of inducing neutralizing antibodies in vivo. In this study, a DNA vaccine pPI-2.EGFP.VP7.S co-expressing VP7 protein of PoRV and S protein of PEDV was constructed. Six 8-week-old mice were immunized with the recombinant plasmid pPI-2.EGFP.VP7.S. The high humoral immune responses (virus specific antibody) and cellular immune responses (IFN-γ, IL-4, and spleen lymphocyte proliferation) were evaluated. The immune effect through intramuscular injection increased with plasmid dose when compared with subcutaneous injection. The immune-enhancing effect of IFN-α adjuvant was excellent compared with pig spleen transfer factor and IL-12 adjuvant. These results demonstrated that pPI-2.EGFP.VP7.S possess the immunological functions of the VP7 proteins of PoRV and S proteins of PEDV, indicating that pPI-2.EGFP.VP7.S is a candidate vaccine for porcine rotaviral infection (PoR) and porcine epidemic diarrhea (PED).",,"['Yin, Yue', 'Zhu, Ling', 'Liu, Pengjuan', 'Zhao, Jun', 'Fan, Yi', 'Sun, Xiangang', 'Xu, Zhiwen']",,,,
,PMC,PSXIII-19 Swine Health Health and Management Evaluation in American Samoa.,http://dx.doi.org/10.1093/jas/sky404.568,PMC6285338,,,"American Samoa is working to improve swine production genetics and management. Our objective was to identify health and management factors affecting swine performance. A1998 survey found six leptospirosis serovars and parvovirus and heavy parasites loads, but no brucellosis or pseudorabies. Our 2016 Artificial Insemination Training focused on improving genetics and resulted in 12 sows bred and 103 piglets born. Oour 2017 Swine Farm Evaluation surveyed 26 farms with an average of 9 sows per farm. Serological samples were tested for antibodies against Porcine Circovirus Type 2b (ELISA, 96% positive), Swine Influenza (ELISA, 31%), Senecavirus (IFA, 27%), Mycoplasma hyopneumoniae (ELISA, 15%), Porcine Epidemic Diarrhea (IFA, 15%), and Porcine Reproductive and Respiratory Syndrome (ELISA, 4%, 1 pig). o evidence was seen of Porcine Respiratory Coronavirus (ELISA), Transmissable Gastroenteritis (ELISA) or Pseudorabies (SN). Fecal samples contained Ascaris suum, Oesophagostomum dentatum, Stephanurus dentatus, and, less commonly, Strongyles nodular worm, Stronglyloides, Brachylaemus suis, Necator species, Trichuris suis, and Fasciolopsis buski. Ear scrapings and scratching behavior indicated the presence of sarcoptic mange (31% of farms). Most farms fed a 14% grain feed (88% of farms) and local feeds (coconut, vegetables, fruits, 69%); only one farm fed an 18% starter and one fed milk to young pigs. One or more thin pigs were seen on 46% of farms. Waste is managed either by wash down (85% of farms) or as dry litter (42%); some farms used both. Wastewater concerns led to water restriction on 12% of farms. In conclusion, parasites and suboptimal feeding are constraints on pig growth and performance. Management recommendations to improve production should address these, in addition to improving health and genetics.",,"['Zaleski, H', 'Petznick, T', 'Hansell, M', 'Uta, F', 'Gurr, I']",,,,
,PMC,Evolutionary Virology at 40,http://dx.doi.org/10.1534/genetics.118.301556,PMC6283181,,,"RNA viruses are diverse, abundant, and rapidly evolving. Genetic data have been generated from virus populations since the late 1970s and used to understand their evolution, emergence, and spread, culminating in the generation and analysis of many thousands of viral genome sequences. Despite this wealth of data, evolutionary genetics has played a surprisingly small role in our understanding of virus evolution. Instead, studies of RNA virus evolution have been dominated by two very different perspectives, the experimental and the comparative, that have largely been conducted independently and sometimes antagonistically. Here, we review the insights that these two approaches have provided over the last 40 years. We show that experimental approaches using in vitro and in vivo laboratory models are largely focused on short-term intrahost evolutionary mechanisms, and may not always be relevant to natural systems. In contrast, the comparative approach relies on the phylogenetic analysis of natural virus populations, usually considering data collected over multiple cycles of virus–host transmission, but is divorced from the causative evolutionary processes. To truly understand RNA virus evolution it is necessary to meld experimental and comparative approaches within a single evolutionary genetic framework, and to link viral evolution at the intrahost scale with that which occurs over both epidemiological and geological timescales. We suggest that the impetus for this new synthesis may come from methodological advances in next-generation sequencing and metagenomics.",,"['Geoghegan, Jemma L.', 'Holmes, Edward C.']",,,,
,PMC,Congenital Cytomegalovirus Infection Alters Olfaction Before Hearing Deterioration In Mice,http://dx.doi.org/10.1523/JNEUROSCI.0740-18.2018,PMC6596252,,,"In developed countries, cytomegalovirus (CMV)-infected newborns are at high risk of developing sensorineural handicaps such as hearing loss, requiring extensive follow-up. However, early prognostic tools for auditory damage in children are not yet available. In the fetus, CMV infection leads to early olfactory bulb (OB) damage, suggesting that olfaction might represent a valuable prognosis for neurological outcome of this viral infection. Here, we demonstrate that in utero CMV inoculation causes fetal infection and growth retardation in mice of both sexes. It disrupts OB normal development, leading to disproportionate OB cell layers and rapid major olfactory deficits. Olfaction is impaired as early as day 6 after birth in both sexes, long before the emergence of auditory deficits. Olfactometry in males reveals a long-lasting alteration in olfactory perception and discrimination, particularly in binary mixtures of monomolecular odorants. Although sensory inputs to the OB remain unchanged, hallmarks of autophagy are increased in the OB of 3-postnatal week-old mice, leading to local neuroinflammation and loss of neurons expressing tyrosine hydroxylase and calbindin. At the cellular level, we found CMV-infected cells and an increased number of apoptotic cells scattered throughout the OB layers, whereas cell proliferation in the neurogenic subventricular zone was decreased. These cellular observations were long-lasting, persisting up to 16 weeks after birth in both males and females and thus providing a mechanism supporting olfactory loss. Despite obvious differences in neurogenesis between human and mouse, these findings offer new strategies aimed at early detection of neurological dysfunctions caused by congenital infections. SIGNIFICANCE STATEMENT In developed countries, congenital cytomegalovirus (CMV)-infected newborns are at high risk of developing sensory handicaps such as hearing loss, thus requiring prolonged follow-up. In this study, we describe for the first time the functional impact of congenital CMV infection on the olfactory system and its associated sense of smell. We demonstrate that a mouse model of congenital CMV infection shows defects in olfactory bulb (OB) normal development and pronounced olfactory deficits affecting acuity and discrimination of odorants. These major olfactory deficits occur long before the emergence of auditory deficits through the upregulation of OB autophagy inducing local neuroinflammation and altered neuron content. Our findings provide new opportunities for designing olfactory means to monitor the possible neurological outcome during congenital CMV infection.",,"['Lazarini, Françoise', 'Katsimpardi, Lida', 'Levivien, Sarah', 'Wagner, Sébastien', 'Gressens, Pierre', 'Teissier, Natacha', 'Lledo, Pierre-Marie']",,,,
,PMC,Phosphorylation cascade regulates the formation and maturation of rotaviral replication factories,http://dx.doi.org/10.1073/pnas.1717944115,PMC6304940,,,"The rotavirus (RV) genome is replicated and packaged into virus progeny in cytoplasmic inclusions called viroplasms, which require interactions between RV nonstructural proteins NSP2 and NSP5. How viroplasms form remains unknown. We previously found two forms of NSP2 in RV-infected cells: a cytoplasmically dispersed dNSP2, which interacts with hypophosphorylated NSP5; and a viroplasm-specific vNSP2, which interacts with hyperphosphorylated NSP5. Other studies report that CK1α, a ubiquitous cellular kinase, hyperphosphorylates NSP5, but requires NSP2 for reasons that are unclear. Here we show that silencing CK1α in cells before RV infection resulted in (i) >90% decrease in RV replication, (ii) disrupted vNSP2 and NSP5 interaction, (iii) dispersion of vNSP2 throughout the cytoplasm, and (iv) reduced vNSP2 protein levels. Together, these data indicate that CK1α directly affects NSP2. Accordingly, an in vitro kinase assay showed that CK1α phosphorylates serine 313 of NSP2 and triggers NSP2 octamers to form a lattice structure as demonstrated by crystallographic analysis. Additionally, a dual-specificity autokinase activity for NSP2 was identified and confirmed by mass spectrometry. Together, our studies show that phosphorylation of NSP2 involving CK1α controls viroplasm assembly. Considering that CK1α plays a role in the replication of other RNA viruses, similar phosphorylation-dependent mechanisms may exist for other virus pathogens that require cytoplasmic virus factories for replication.",,"['Criglar, Jeanette M.', 'Anish, Ramakrishnan', 'Hu, Liya', 'Crawford, Sue E.', 'Sankaran, Banumathi', 'Prasad, B. V. Venkataram', 'Estes, Mary K.']",,,,
,PMC,Ontogeny and Biology of Human Small Airway Epithelial Club Cells,http://dx.doi.org/10.1164/rccm.201710-2107OC,PMC6290945,,,"Rationale: Little is known about human club cells, dome-shaped cells with dense cytoplasmic granules and microvilli that represent the major secretory cells of the human small airways (at least sixth-generation bronchi). Objectives: To define the ontogeny and biology of the human small airway epithelium club cell. Methods: The small airway epithelium was sampled from the normal human lung by bronchoscopy and brushing. Single-cell transcriptome analysis and air–liquid interface culture were used to assess club cell ontogeny and biology. Measurements and Main Results: We identified the club cell population by unbiased clustering using single-cell transcriptome sequencing. Principal component gradient analysis uncovered an ontologic link between KRT5 (keratin 5)(+) basal cells and SCGB1A1 (secretoglobin family 1A member 1)(+) club cells, a hypothesis verified by demonstrating in vitro that a pure population of human KRT5(+) SCGB1A1(−) small airway epithelial basal cells differentiate into SCGB1A1(+)KRT5(−) club cells on air–liquid interface culture. Using SCGB1A1 as the marker of club cells, the single-cell analysis identified novel roles for these cells in host defense, xenobiotic metabolism, antiprotease, physical barrier function, monogenic lung disorders, and receptors for human viruses. Conclusions: These observations provide novel insights into the molecular phenotype and biologic functions of the human club cell population and identify basal cells as the human progenitor cells for club cells.",,"['Zuo, Wu-Lin', 'Shenoy, Sushila A.', 'Li, Sheng', 'O’Beirne, Sarah L.', 'Strulovici-Barel, Yael', 'Leopold, Philip L.', 'Wang, Guoqing', 'Staudt, Michelle R.', 'Walters, Matthew S.', 'Mason, Christopher', 'Kaner, Robert J.', 'Mezey, Jason G.', 'Crystal, Ronald G.']",,,,
,PMC,Comparative efficacy of modified-live and inactivated vaccines in boosting responses to bovine respiratory syncytial virus following neonatal mucosal priming of beef calves,,PMC6237255,,,"Bovine respiratory syncytial virus (BRSV) is the leading cause of viral pneumonia in calves, making young passively immune calves candidates for vaccination, and raising issues concerning boosting of neonatally primed responses. To address this, 18, 2-month-old Angus-cross passively immune beef heifer calves that had been primed at birth with a combination viral intranasal vaccine were administered either a parenteral combination vaccine containing modified-live (MLV) BRSV or a similar vaccine containing inactivated BRSV. At 6 months of age, these calves and 2 controls that received only the MLV at 2 months of age were challenged with BRSV via aerosol. Two calves, 1 control, and 1 MLV-boosted, developed severe respiratory disease and required euthanasia; the remaining calves developed no or mild respiratory disease and recovered. Calves that received the inactivated booster had significantly higher arterial oxygen concentrations on Day 7 after challenge and had anamnestic BRSV-specific IgG and neutralizing antibodies after challenge; the MLV-boosted calves did not. These data suggest that adjuvanted inactivated parenteral BRSV vaccines administered at 2 months of age may provide better boosting for neonatally mucosally primed calves.",,"['Ellis, John', 'Gow, Sheryl', 'Berenik, Adam', 'Lacoste, Stacey', 'Erickson, Nathan']",,,,
,PMC,Quiz Corner,,PMC6237253,,,,,,,,,
,PMC,Eomesodermin driven IL-10 production in effector CD8(+) T cells promotes a memory phenotype.,http://dx.doi.org/10.1016/j.cellimm.2018.11.008,PMC6449173,,,"CD8(+) T cell differentiation is controlled by the transcription factors T-bet and Eomesodermin, in concert with the cytokines IL-2, IL-10 and IL-12. Among these pathways, the mechanisms by which T-box proteins and IL-10 interact to promote a memory T cell fate remain poorly understood. Here, we show that Eomes and IL-10 drive a central memory phenotype in murine CD8(+) T cells. Eomes expression led to increased IL-10 expression by the effector CD8(+) T cells themselves as well as an increase in the level of the lymph node homing selectin CD62L. Furthermore, exposure of effector CD8(+) T cells to IL-10 maintained CD62L expression levels in culture. Thus, Eomes promotes a step-wise transition of effector T cells towards a memory phenotype, synergizing with IL-10 to enhance the expression of CD62L. The early augmentation of lymph node homing markers by Eomes may facilitate the retention of effector T cells in the relatively low inflammatory milieu of the secondary lymphoid organs that promotes central memory development.",,"['Reiser, John', 'Sadashivaiah, Kavitha', 'Furusawa, Aki', 'Banerjee, Arnob', 'Singh, Nevil']",,,,
,PMC,Modelling the global spread of diseases: A review of current practice and capability,http://dx.doi.org/10.1016/j.epidem.2018.05.007,PMC6227252,29853411,NO-CC CODE,"Mathematical models can aid in the understanding of the risks associated with the global spread of infectious diseases. To assess the current state of mathematical models for the global spread of infectious diseases, we reviewed the literature highlighting common approaches and good practice, and identifying research gaps. We followed a scoping study method and extracted information from 78 records on: modelling approaches; input data (epidemiological, population, and travel) for model parameterization; model validation data. We found that most epidemiological data come from published journal articles, population data come from a wide range of sources, and travel data mainly come from statistics or surveys, or commercial datasets. The use of commercial datasets may benefit the modeller, however makes critical appraisal of their model by other researchers more difficult. We found a minority of records (26) validated their model. We posit that this may be a result of pandemics, or far-reaching epidemics, being relatively rare events compared with other modelled physical phenomena (e.g. climate change). The sparsity of such events, and changes in outbreak recording, may make identifying suitable validation data difficult. We appreciate the challenge of modelling emerging infections given the lack of data for both model parameterisation and validation, and inherent complexity of the approaches used. However, we believe that open access datasets should be used wherever possible to aid model reproducibility and transparency. Further, modellers should validate their models where possible, or explicitly state why validation was not possible.",2018 Dec,"['Walters, Caroline E.', 'Meslé, Margaux M.I.', 'Hall, Ian M.']",Epidemics,,,
,PMC,Discrete Stochastic Analogs of Erlang Epidemic Models,http://dx.doi.org/10.1080/17513758.2017.1401677,PMC6120589,,,"Erlang differential equation models of epidemic processes provide more realistic disease-class transition dynamics from susceptible (S) to exposed (E) to infectious (I) and removed (R) categories than the ubiquitous SEIR model. The latter is itself is at one end of the spectrum of Erlang SE(m)I(n)R models with m ≥ 1 concatenated E compartments and n ≥ 1 concatenated I compartments. Discrete-time models, however, are computationally much simpler to simulate and fit to epidemic outbreak data than continuous-time differential equations, and are also much more readily extended to include demographic and other types of stochasticity. Here we formulate discrete-time deterministic analogs of the Erlang models, and their stochastic extension, based on a time-to-go distributional principle. Depending on which distributions are used (e.g., discretized Erlang, Gamma, Beta, or Uniform distributions), we demonstrate that our formulation represents both a discretization of Erlang epidemic models and generalizations thereof. We consider the challenges of fitting SE(m)I(n)R models and our discrete-time analog to data (the recent outbreak of Ebola in Liberia). We demonstrate that the latter performs much better than the former; although confining fits to strict SEIR formulations reduces the numerical challenges, but sacrifices best-fit likelihood scores by at least 7%.",,"['Getz, Wayne M.', 'Dougherty, Eric R.']",,,,
,PMC,Antibiotic Recommendations for Acute Otitis Media and Acute Bacterial Sinusitis: Conundrum No More,http://dx.doi.org/10.1097/INF.0000000000002009,PMC6151174,,,There has been a substantial change in the prevalence and microbiologic characteristics of cases of acute otitis media secondary to the widespread use of pneumococcal conjugate vaccines. Current trends in nasopharyngeal colonization and the microbiology of acute otitis media support a change in the recommendation for antibiotic management of acute otitis media and acute bacterial sinusitis in children.,,"['Wald, Ellen R.', 'DeMuri, Gregory P.']",,,,
,PMC,Humoral Immunodeficiencies: Conferred Risk of Infections and Benefits of Immunoglobulin Replacement Therapy,http://dx.doi.org/10.1111/trf.15020,PMC6939302,,,"Primary immune deficiency diseases (PIDDs) result from genetic defects of the immune system that increase patients’ susceptibility to infections. The types of infections that occur in PIDD patients are largely dictated by the nature of the immune deficiency, which can be defined by dysfunction of cellular or humoral defenses. An increasing number of PIDDs, including those with both cellular and humoral defects, have antibody deficiency as a major feature and can benefit from immunoglobulin replacement therapy as a result. In fact, the most common PIDDs worldwide are antibody deficiencies and include common variable immunodeficiency, congenital agammaglobulinemia, hyper IgM syndrome, specific antibody deficiency, and Good syndrome. While immunoglobulin replacement therapy is the cornerstone of treatment for the majority of these conditions, a thorough understanding of the specific infections for which these patients are at increased risk can hasten diagnosis and guide additional therapies. Moreover, the infection trends in some PIDD patients with profound defects of cellular immunity, such as autosomal dominant hyper IgE syndrome (Job’s/Buckley’s Syndrome) or dedicator of cytokinesis 8 (DOCK8) deficiency, suggest that select patients might benefit from immunoglobulin replacement therapy even if their immune deficiency is not limited to antibody defects. In this review, we provide an overview of the predisposition to infections seen in PIDDs that may benefit from immunoglobulin replacement therapy.",,"['Gernez, Yael', 'Baker, Mary Grace', 'Maglione, Paul J.']",,,,
,PMC,From Theory to Practice: Translating Whole-Genome Sequencing (WGS) into the Clinic,http://dx.doi.org/10.1016/j.tim.2018.08.004,PMC6249990,30193960,CC BY,"Hospitals worldwide are facing an increasing incidence of hard-to-treat infections. Limiting infections and providing patients with optimal drug regimens require timely strain identification as well as virulence and drug-resistance profiling. Additionally, prophylactic interventions based on the identification of environmental sources of recurrent infections (e.g., contaminated sinks) and reconstruction of transmission chains (i.e., who infected whom) could help to reduce the incidence of nosocomial infections. WGS could hold the key to solving these issues. However, uptake in the clinic has been slow. Some major scientific and logistical challenges need to be solved before WGS fulfils its potential in clinical microbial diagnostics. In this review we identify major bottlenecks that need to be resolved for WGS to routinely inform clinical intervention and discuss possible solutions.",2018 Dec,"['Balloux, Francois', 'Brønstad Brynildsrud, Ola', 'van Dorp, Lucy', 'Shaw, Liam P.', 'Chen, Hongbin', 'Harris, Kathryn A.', 'Wang, Hui', 'Eldholm, Vegard']",Trends Microbiol,,,
,PMC,The occurrence of polyomaviruses WUPyV and KIPyV among patients with severe respiratory infections,http://dx.doi.org/10.1007/s42770-018-0038-x,PMC6863251,,,"In 2007, the new polyomaviruses WUPyV and KIPyV were identified in patients with acute respiratory infections. The aim of this study was to investigate these viruses in hospitalized patients with severe acute respiratory infection (SARI). A retrospective study was conducted with 251 patients, from April 2009 to November 2010, using nasopharyngeal aspirates, naso- and oropharyngeal swab samples from hospitalized patients (children < 12 years and adults) who had SARI within 7 days of the onset of symptoms, including fever (> 38.8 °C), dyspnea, and cough. Clinical and epidemiological information was obtained through standardized questionnaire. Enrolled patients were initially suspected to have influenza A(H1N1)pdm09 infections. WUPyV and KIPyV were detected by real-time PCR. Samples were also tested for influenza A and B viruses, human respiratory syncytial virus, rhinovirus, metapneumovirus, coronavirus, adenovirus, and parainfluenza viruses. WUPyV and KIPyV were detected in 6.77% (4.78% and 1.99%, respectively) of hospitalized patients with SARI. All samples from children showed coinfections (rhinovirus was the most commonly detected). Six adults had polyomavirus infection and four (1.6%) had monoinfection. Of them, 3 reported comorbidities including immunosuppression and 1 patient had worse outcome, requiring ICU admission. These preliminary data may suggest a possible role of polyomaviruses in SARI among immunocompromised adult patients.",,"['Caldeira, Débora Bellini', 'de Souza Luna, Luciano Kleber', 'Watanabe, Aripuana', 'Perosa, Ana Helena', 'Granato, Celso', 'Bellei, Nancy']",,,,
,PMC,Isolation and genome characterization of canine parvovirus type 2c in Brazil,http://dx.doi.org/10.1007/s42770-018-0036-z,PMC6863306,,,"This study focused on the isolation and characterization of parvovirus in an infected dog in midwestern Brazil. Non-enveloped icosahedral parvovirus-like particles were isolated in CRFK cells and were allocated to a clade comprised of strains of CPV-2c, based on genome analysis. This is the first isolate of CPV-2c genomically characterized in Brazil.",,"['Jaune, Felipe Wolf', 'Taques, Isis Indaiara Gonçalves Granjeiro', 'dos Santos Costa, Jackeliny', 'Araújo, João Pessoa', 'Catroxo, Márcia H. B.', 'Nakazato, Luciano', 'de Aguiar, Daniel Moura']",,,,
,PMC,Phenotypic Prioritization of Diphyllin Derivatives that Block Filo-viral Cell Entry by Vacuolar (H(+))-ATPase Inhibition,http://dx.doi.org/10.1002/cmdc.201800587,PMC6387451,,,"Many viruses utilize endosomal pathways to gain entry to cells and propagate infection. Sensing of endosomal acidification is a trigger for release of many virus cores into the cell cytosol. Previous efforts with inhibitors of vacuolar-ATPase have been shown to block endosomal acidification and affect viral entry albeit with limited potential for therapeutic selectivity. Herein, four novel series of derivatives of the vacuolar-ATPase inhibitor diphyllin were synthesized to assess their potential for enhancing potency and anti-filoviral activity over cytotoxicity. Derivatives that suitably blocked cellular entry of Ebola pseudo-typed virus were further evaluated as inhibitors of endosomal acidification and isolated human Vacuolar-ATPase activity. Several compounds with significant increases in potency over diphyllin in these assays also separated from cytotoxic doses in human cell models by >100 fold. Finally, three derivatives were shown to be inhibitors of replication-competent Ebola viral entry into primary macrophages with comparable potencies and enhanced selectivity toward anti-viral activity.",,"['Lindstrom, Aaron', 'Anantpadma, Manu', 'Baker, Logan', 'Raghavendra, N.M.', 'Davey, Robert', 'Davisson, Vincent Jo']",,,,
,PMC,"Use of the Staged Development Tool for Assessing, Planning, and Measuring Progress in the Development of National Public Health Institutes",http://dx.doi.org/10.1089/hs.2018.0044,PMC6260584,,,"The Staged Development Tool (SDT) was created to help National Public Health Institutes (NPHIs) assess their current capacity and develop roadmaps for achieving a higher level of functioning. The paper discusses the current use of the SDT by NPHIs to establish baseline capacity and inform strategic planning, and its proposed use in a three-step sequence for measuring the impact of capacity-building interventions over time. The paper also includes descriptions of how NPHIs have been using the SDT to assess their baseline capacity in management issues and core public health functions. The first use of the SDT by an NPHI provides essential baseline information on their capacities and levels of functioning, and plans for addressing gaps. By repeating the SDT after time for the plans to be implemented, the SDT can be used to evaluate changes in capacity and the effectiveness of the interventions made. Because the SDT is built to be complementary to existing assessments and public health strengthening tools and guidelines, implementing the SDT provides concrete, complementary information that can help countries achieve global health security goals and address current and future threats to public health.",,"['Barzilay, Ezra J.', 'Vandi, Henry', 'Binder, Sue', 'Udo, Ifeyinwa', 'Ospina, Martha L', 'Ihekweazu, Chikwe', 'Bratton, Shelly']",,,,
,PMC,Detection of Viruses in Clinical Samples by Use of Metagenomic Sequencing and Targeted Sequence Capture,http://dx.doi.org/10.1128/JCM.01123-18,PMC6258860,,,"Metagenomic shotgun sequencing (MSS) is a revolutionary approach to viral diagnostic testing that allows simultaneous detection of a broad range of viruses, detailed taxonomic assignment, and detection of mutations associated with antiviral drug resistance. To enhance sensitivity for virus detection, we previously developed ViroCap, a targeted sequence capture panel designed to enrich nucleic acid from a comprehensive set of eukaryotic viruses prior to sequencing. To demonstrate the utility of MSS with targeted sequence capture for detecting clinically important viruses and characterizing clinically important viral features, we used ViroCap to analyze clinical samples from a diagnostic virology laboratory containing a broad range of medically relevant viruses. From 26 samples, MSS with ViroCap detected all of the expected viruses and 30 additional viruses. Comparing sequencing after capture enrichment with standard MSS, we detected 13 viruses only with capture enrichment and observed a consistent increase in the number and percentage of viral sequence reads as well as the breadth and depth of coverage of the viral genomes. Compared with clinical testing, MSS enhanced taxonomic assignment for 15 viruses, and codons associated with antiviral drug resistance in influenza A virus, herpes simplex virus (HSV), human immunodeficiency virus (HIV), and hepatitis C virus (HCV) could be analyzed. Overall, in clinical samples, MSS with targeted sequence capture provides enhanced virus detection and information of clinical and epidemiologic relevance compared with clinical testing and MSS without targeted sequence capture.",,"['Wylie, Kristine M.', 'Wylie, Todd N.', 'Buller, Richard', 'Herter, Brandi', 'Cannella, Maria T.', 'Storch, Gregory A.']",,,,
,PMC,Virulent Pseudorabies Virus Infection Induces a Specific and Lethal Systemic Inflammatory Response in Mice,http://dx.doi.org/10.1128/JVI.01614-18,PMC6258956,,,"Pseudorabies virus (PRV) is an alphaherpesvirus that infects the peripheral nervous system (PNS). The natural host of PRV is the swine, but it can infect most mammals, including cattle, rodents, and dogs. In these nonnatural hosts, PRV always causes a severe acute and lethal neuropathy called the “mad itch,” which is uncommon in swine. Thus far, the pathophysiological and immunological processes leading to the development of the neuropathic itch and the death of the animal are unclear. Using a footpad inoculation model, we established that mice inoculated with PRV-Becker (virulent strain) develop a severe pruritus in the foot and become moribund at 82 h postinoculation (hpi). We found necrosis and inflammation with a massive neutrophil infiltration only in the footpad and dorsal root ganglia (DRGs) by hematoxylin and eosin staining. PRV load was detected in the foot, PNS, and central nervous system tissues by quantitative reverse transcription-PCR. Infected mice had elevated plasma levels of proinflammatory cytokines (interleukin-6 [IL-6] and granulocyte colony-stimulating factor [G-CSF]) and chemokines (Gro-1 and monocyte chemoattractant protein 1). Significant IL-6 and G-CSF levels were detected in several tissues at 82 hpi. High plasma levels of C-reactive protein confirmed the acute inflammatory response to PRV-Becker infection. Moreover, mice inoculated with PRV-Bartha (attenuated, live vaccine strain) did not develop pruritus at 82 hpi. PRV-Bartha also replicated in the PNS, and the infection spread further in the brain than PRV-Becker. PRV-Bartha infection did not induce the specific and lethal systemic inflammatory response seen with PRV-Becker. Overall, we demonstrated the importance of inflammation in the clinical outcome of PRV infection in mice and provide new insights into the process of PRV-induced neuroinflammation. IMPORTANCE Pseudorabies virus (PRV) is an alphaherpesvirus related to human pathogens such as herpes simplex virus 1 and varicella-zoster virus (VZV). The natural host of PRV is the swine, but it can infect most mammals. In susceptible animals other than pigs, PRV infection always causes a characteristic lethal pruritus known as the “mad itch.” The role of the immune response in the clinical outcome of PRV infection is still poorly understood. Here, we show that a systemic host inflammatory response is responsible for the severe pruritus and acute death of mice infected with virulent PRV-Becker but not mice infected with attenuated strain PRV-Bartha. In addition, we identified IL-6 and G-CSF as two main cytokines that play crucial roles in the regulation of this process. Our findings give new insights into neuroinflammatory diseases and strengthen further the similarities between VZV and PRV infections at the level of innate immunity.",,"['Laval, K.', 'Vernejoul, J. B.', 'Van Cleemput, J.', 'Koyuncu, O. O.', 'Enquist, L. W.']",,,,
,PMC,Salinomycin Inhibits Influenza Virus Infection by Disrupting Endosomal Acidification and Viral Matrix Protein 2 Function,http://dx.doi.org/10.1128/JVI.01441-18,PMC6258947,,,"Screening of chemical libraries with 2,000 synthetic compounds identified salinomycin as a hit against influenza A and B viruses, with 50% effective concentrations ranging from 0.4 to 4.3 μM in cells. This compound is a carboxylic polyether ionophore that exchanges monovalent ions for protons across lipid bilayer membranes. Monitoring the time course of viral infection showed that salinomycin blocked nuclear migration of viral nuclear protein (NP), the most abundant component of the viral ribonucleoprotein (vRNP) complex. It caused cytoplasmic accumulation of NP, particularly within perinuclear endosomes, during virus entry. This was primarily associated with failure to acidify the endosomal-lysosomal compartments. Similar to the case with amantadine (AMT), proton channel activity of viral matrix protein 2 (M2) was blocked by salinomycin. Using purified retroviral Gag-based virus-like particles (VLPs) with M2, it was proved that salinomycin directly affects the kinetics of a proton influx into the particles but in a manner different from that of AMT. Notably, oral administration of salinomycin together with the neuraminidase inhibitor oseltamivir phosphate (OSV-P) led to enhanced antiviral effect over that with either compound used alone in influenza A virus-infected mouse models. These results provide a new paradigm for developing antivirals and their combination therapy that control both host and viral factors. IMPORTANCE Influenza virus is a main cause of viral respiratory infection in humans as well as animals, occasionally with high mortality. Circulation of influenza viruses resistant to the matrix protein 2 (M2) inhibitor, amantadine, is highly prevalent. Moreover, the frequency of detection of viruses resistant to the neuraminidase inhibitors, including oseltamivir phosphate (OSV-P) or zanamivir, is also increasing. These issues highlight the need for discovery of new antiviral agents with different mechanisms. Salinomycin as the monovalent cation-proton antiporter exhibited consistent inhibitory effects against influenza A and B viruses. It plays multifunctional roles by blocking endosomal acidification and by inactivating the proton transport function of M2, the key steps for influenza virus uncoating. Notably, salinomycin resulted in marked therapeutic effects in influenza virus-infected mice when combined with OSV-P, suggesting that its chemical derivatives could be developed as an adjuvant antiviral therapy to treat influenza infections resistant or less sensitive to existing drugs.",,"['Jang, Yejin', 'Shin, Jin Soo', 'Yoon, Yi-Seul', 'Go, Yun Young', 'Lee, Hye Won', 'Kwon, Oh Seung', 'Park, Sehee', 'Park, Man-Seong', 'Kim, Meehyein']",,,,
,PMC,Mapping the Nonstructural Protein Interaction Network of Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1128/JVI.01112-18,PMC6258939,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-stranded RNA virus belonging to the family Arteriviridae. Synthesis of the viral RNA is directed by replication/transcription complexes (RTC) that are mainly composed of a network of PRRSV nonstructural proteins (nsps) and likely cellular proteins. Here, we mapped the interaction network among PRRSV nsps by using yeast two-hybrid screening in conjunction with coimmunoprecipitation (co-IP) and cotransfection assays. We identified a total of 24 novel interactions and found that the interactions were centered on open reading frame 1b (ORF1b)-encoded nsps that were mainly connected by the transmembrane proteins nsp2, nsp3, and nsp5. Interestingly, the interactions of the core enzymes nsp9 and nsp10 with transmembrane proteins did not occur in a straightforward manner, as they worked in the co-IP assay but were poorly capable of finding each other within intact mammalian cells. Further proof that they can interact within cells required the engineering of N-terminal truncations of both nsp9 and nsp10. However, despite the poor colocalization relationship in cotransfected cells, both nsp9 and nsp10 came together with membrane proteins (e.g., nsp2) at the viral replication and transcription complexes (RTC) in PRRSV-infected cells. Thus, our results indicate the existence of a complex interaction network among PRRSV nsps and raise the possibility that the recruitment of key replicase proteins to membrane-associated nsps may involve some regulatory mechanisms during infection. IMPORTANCE Synthesis of PRRSV RNAs within host cells depends on the efficient and correct assembly of RTC that takes places on modified intracellular membranes. As an important step toward dissecting this poorly understood event, we investigated the interaction network among PRRSV nsps. Our studies established a comprehensive interaction map for PRRSV nsps and revealed important players within the network. The results also highlight the likely existence of a regulated recruitment of the PRRSV core enzymes nsp9 and nsp10 to viral membrane nsps during PRRSV RTC assembly.",,"['Song, Jiangwei', 'Liu, Yuanyuan', 'Gao, Peng', 'Hu, Yunhao', 'Chai, Yue', 'Zhou, Shaochuan', 'Kong, Can', 'Zhou, Lei', 'Ge, Xinna', 'Guo, Xin', 'Han, Jun', 'Yang, Hanchun']",,,,
,PMC,Lysosomal Proteases Are a Determinant of Coronavirus Tropism,http://dx.doi.org/10.1128/JVI.01504-18,PMC6258935,,,"Cell entry by coronaviruses involves two principal steps, receptor binding and membrane fusion; the latter requires activation by host proteases, particularly lysosomal proteases. Despite the importance of lysosomal proteases in both coronavirus entry and cell metabolism, the correlation between lysosomal proteases and cell tropism of coronaviruses has not been established. Here, we examined the roles of lysosomal proteases in activating coronavirus surface spike proteins for membrane fusion, using the spike proteins from severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) as the model system. To this end, we controlled the contributions from receptor binding and other host proteases, thereby attributing coronavirus entry solely or mainly to the efficiency of lysosomal proteases in activating coronavirus spike-mediated membrane fusion. Our results showed that lysosomal proteases from bat cells support coronavirus spike-mediated pseudovirus entry and cell-cell fusion more effectively than their counterparts from human cells. Moreover, purified lysosomal extracts from bat cells cleave cell surface-expressed coronavirus spikes more efficiently than their counterparts from human cells. Overall, our study suggests that different lysosomal protease activities from different host species and tissue cells are an important determinant of the species and tissue tropism of coronaviruses. IMPORTANCE Coronaviruses are capable of colonizing new species, as evidenced by the recent emergence of SARS and MERS coronaviruses; they can also infect multiple tissues in the same species. Lysosomal proteases play critical roles in coronavirus entry by cleaving coronavirus surface spike proteins and activating the fusion of host and viral membranes; they also play critical roles in cell physiology by processing cellular products. How do different lysosomal protease activities from different cells impact coronavirus entry? Here, we controlled the contributions from known factors that function in coronavirus entry so that lysosomal protease activities became the only or the main determinant of coronavirus entry. Using pseudovirus entry, cell-cell fusion, and biochemical assays, we showed that lysosomal proteases from bat cells activate coronavirus spike-mediated membrane fusion more efficiently than their counterparts from human cells. Our study provides the first direct evidence supporting lysosomal proteases as a determinant of the species and tissue tropisms of coronaviruses.",,"['Zheng, Yuan', 'Shang, Jian', 'Yang, Yang', 'Liu, Chang', 'Wan, Yushun', 'Geng, Qibin', 'Wang, Michelle', 'Baric, Ralph', 'Li, Fang']",,,,
,PMC,Nitazoxanide Is a Therapeutic Option for Adenovirus-Related Enteritis in Immunocompromised Adults,http://dx.doi.org/10.1128/AAC.01937-18,PMC6256758,,,,,"['Esquer Garrigos, Zerelda', 'Barth, Dylan', 'Hamdi, Ahmed M.', 'Abu Saleh, Omar M.', 'Sohail, M. Rizwan']",,,,
,PMC,Identification of Mycobacterium genavense natural infection in a domestic ferret,http://dx.doi.org/10.1177/1040638718812137,PMC6505761,,,"A 6-y-old neutered male ferret (Mustela putorius furo) was presented because of a 1-mo history of progressive weight loss, chronic cough, and hair loss. On clinical examination, the animal was coughing, slightly depressed, moderately hypothermic, and had bilateral epiphora. Thoracic radiography was suggestive of severe multinodular interstitial pneumonia. Abdominal ultrasound examination revealed hepatosplenomegaly and mesenteric and pancreaticoduodenal lymphadenopathy. Fine-needle aspiration of the pancreaticoduodenal lymph node, followed by routine Romanowsky and Ziehl–Neelsen stains, revealed numerous macrophages containing myriad acid-fast bacilli, leading to identification of mycobacteriosis. Autopsy and histologic examination confirmed the presence of disseminated, poorly defined, acid-fast, bacilli-rich granulomas in the pancreaticoduodenal and mesenteric lymph nodes, intestines, and lungs. Destaining of May-Grünwald/Giemsa–stained slides with alcohol, and then restaining with Ziehl–Neelsen, revealed acid-fast rods and avoided repeat tissue sampling without affecting the Ziehl–Neelsen stain quality and cytologic features. Tissue samples were submitted for a PCR assay targeting the heat shock protein gene (hsp65) and revealed 100% homology with Mycobacterium genavense. We emphasize the use of special stains and PCR for identification of this potential zoonotic agent.",,"['Dequéant, Bérengère', 'Pascal, Quentin', 'Bilbault, Héloïse', 'Dagher, Elie', 'Boschiroli, Maria-Laura', 'Cordonnier, Nathalie', 'Reyes-Gomez, Edouard']",,,,
,PMC,An Upstream Protein-Coding Region in Enteroviruses Modulates Virus Infection in Gut Epithelial Cells,http://dx.doi.org/10.1038/s41564-018-0297-1,PMC6443042,,,"Enteroviruses comprise a large group of mammalian pathogens that includes poliovirus. Pathology in humans ranges from sub-clinical to acute flaccid paralysis, myocarditis and meningitis. Until now, all the enteroviral proteins were thought to derive from proteolytic processing of a polyprotein encoded in a single open reading frame (ORF). We report that many enterovirus genomes also harbor an upstream ORF (uORF) that is subject to strong purifying selection. Using echovirus 7 and poliovirus 1, we confirmed expression of uORF protein (UP) in infected cells. Using ribosome profiling (a technique for global footprinting of translating ribosomes), we also demonstrated translation of the uORF in representative members of the predominant human enterovirus species, namely Enterovirus A, B, and C. In differentiated human intestinal organoids, UP-knockout echoviruses are attenuated compared to wild-type virus at late stages of infection where membrane-associated UP facilitates virus release. Thus we have identified a previously unknown enterovirus protein that facilitates virus growth in gut epithelial cells – the site of initial viral invasion into susceptible hosts. These findings overturn the 50-year-old dogma that enteroviruses use a single-polyprotein gene expression strategy, and have important implications for understanding enterovirus pathogenesis.",,"['Lulla, Valeria', 'Dinan, Adam M.', 'Hosmillo, Myra', 'Chaudhry, Yasmin', 'Sherry, Lee', 'Irigoyen, Nerea', 'Nayak, Komal M.', 'Stonehouse, Nicola J.', 'Zilbauer, Matthias', 'Goodfellow, Ian', 'Firth, Andrew E.']",,,,
,PMC,Defining the interval for monitoring potential adverse events following immunization (AEFIs) after receipt of live viral vectored vaccines,http://dx.doi.org/10.1016/j.vaccine.2018.08.085,PMC6535369,,,"Live viral vectors that express heterologous antigens of the target pathogen are being investigated in the development of novel vaccines against serious infectious agents like HIV and Ebola. As some live recombinant vectored vaccines may be replication-competent, a key challenge is defining the length of time for monitoring potential adverse events following immunization (AEFI) in clinical trials and epidemiologic studies. This time period must be chosen with care and based on considerations of pre-clinical and clinical trials data, biological plausibility and practical feasibility. The available options include: 1) adapting from the current relevant regulatory guidelines; 2) convening a panel of experts to review the evidence from a systematic literature search to narrow down a list of likely potential or known AEFI and establish the optimal risk window(s); and 3) conducting “near real-time” prospective monitoring for unknown clustering’s of AEFI in validated large linked vaccine safety databases using Rapid Cycle Analysis for pre-specified adverse events of special interest (AESI) and Treescan to identify previously unsuspected outcomes. The risk window established by any of these options could be used along with 4) establishing a registry of clinically validated pre-specified AESI to include in case-control studies. Depending on the infrastructure, human resources and databases available in different countries, the appropriate option or combination of options can be determined by regulatory agencies and investigators.",,"['Kochhar, Sonali', 'Excler, Jean-Louis', 'Bok, Karin', 'Gurwith, Marc', 'McNeil, Michael M.', 'Seligman, Stephen J.', 'Khuri-Bulos, Najwa', 'Klug, Bettina', 'Laderoute, Marian', 'Robertson, James S.', 'Singh, Vidisha', 'Chen, Robert T', None]",,,,
,PMC,A Real-Time Autonomous Dashboard for the Emergency Department: 5-Year Case Study,http://dx.doi.org/10.2196/10666,PMC6284143,30467100,CC BY,"BACKGROUND: The task of monitoring and managing the entire emergency department (ED) is becoming more important due to increasing pressure on the ED. Recently, dashboards have received the spotlight as health information technology to support these tasks. OBJECTIVE: This study aimed to describe the development of a real-time autonomous dashboard for the ED and to evaluate perspectives of clinical staff on its usability. METHODS: We developed a dashboard based on three principles—“anytime, anywhere, at a glance;” “minimal interruption to workflow;” and “protect patient privacy”—and 3 design features—“geographical layout,” “patient-level alert,” and “real-time summary data.” Items to evaluate the dashboard were selected based on the throughput factor of the conceptual model of ED crowding. Moreover, ED physicians and nurses were surveyed using the system usability scale (SUS) and situation awareness index as well as a questionnaire we created on the basis of the construct of the Situation Awareness Rating Technique. RESULTS: The first version of the ED dashboard was successfully launched in 2013, and it has undergone 3 major revisions since then because of geographical changes in ED and modifications to improve usability. A total of 52 ED staff members participated in the survey. The average SUS score of the dashboard was 67.6 points, which indicates “OK-to-Good” usability. The participants also reported that the dashboard provided efficient “concentration support” (4.15 points), “complexity representation” (4.02 points), “variability representation” (3.96 points), “information quality” (3.94 points), and “familiarity” (3.94 points). However, the “division of attention” was rated at 2.25 points. CONCLUSIONS: We developed a real-time autonomous ED dashboard and successfully used it for 5 years with good evaluation from users.",2018 Nov 22,"['Yoo, Junsang', 'Jung, Kwang Yul', 'Kim, Taerim', 'Lee, Taerim', 'Hwang, Sung Yeon', 'Yoon, Hee', 'Shin, Tae Gun', 'Sim, Min Seob', 'Jo, Ik Joon', 'Paeng, Hansol', 'Choi, Jong Soo', 'Cha, Won Chul']",JMIR Mhealth Uhealth,,,
,PMC,Virus-virus interactions and host ecology are associated with RNA virome structure in wild birds,http://dx.doi.org/10.1111/mec.14918,PMC6312746,,,"Little is known about the factors that shape the ecology of RNA viruses in nature. Wild birds are an important case in point, as other than influenza A virus, avian samples are rarely tested for viruses, especially in the absence of overt disease. Using bulk RNA-sequencing (‘meta-transcriptomics’) we revealed the viral diversity present in Australian wild birds through the lens of the ecological factors that may determine virome structure and abundance. A meta-transcriptomic analysis of four Anseriformes (waterfowl) and Charadriiformes (shorebird) species sampled in temperate and arid Australia revealed the presence of 27 RNA virus genomes, 18 of which represent newly described species. The viruses identified included a previously described gammacoronavirus and influenza A viruses. Additionally, we identified novel virus species from the families Astroviridae, Caliciviridae, Reoviridae, Rhabdoviridae, Picobirnaviridae, and Picornaviridae. We noted differences in virome structure that reflected underlying differences in location and influenza A infection status. Red-necked avocets (Recurvirostra novaehollandiae) from Australia’s arid interior possessed the greatest viral diversity and abundance, markedly higher than individuals sampled in temperate Australia. In Ruddy Turnstones (Arenaria interpres) and dabbling ducks (Anas spp.) viral abundance and diversity was higher and more similar in hosts that were positive for influenza A infection compared to those that were negative for this virus, despite samples being collected on the same day and from the same location. This study highlights the extent and diversity of RNA viruses in wild birds, and lays the foundation for understanding the factors that determine virome structure in wild populations.",,"['Wille, Michelle', 'Eden, John-Sebastian', 'Shi, Mang', 'Klaassen, Marcel', 'Hurt, Aeron C.', 'Holmes, Edward C.']",,,,
,PMC,"Award Winners and Abstracts of the 32nd Annual Symposium of The Protein Society; Boston, MA, July 9–12, 2018",http://dx.doi.org/10.1002/pro.3513,PMC6247239,,,,,,,,,
,PMC,A high-throughput inhibition assay to study MERS-CoV antibody interactions using image cytometry,http://dx.doi.org/10.1016/j.jviromet.2018.11.009,PMC6357230,,,"The emergence of new pathogens, such as Middle East respiratory syndrome coronavirus (MERS-CoV), poses serious challenges to global public health and highlights the urgent need for methods to rapidly identify and characterize potential therapeutic or prevention options, such as neutralizing antibodies. Spike (S) proteins are present on the surface of MERS-CoV virions and mediate viral entry. S is the primary target for MERS-CoV vaccine and antibody development, and it has become increasingly important to understand MERS-CoV antibody binding specificity and function. Commonly used serological methods like ELISA, biolayer interferometry, and flow cytometry are informative, but limited. Here, we demonstrate a high-throughput protein binding inhibition assay using image cytometry. The image cytometry-based high-throughput screening method was developed by selecting a cell type with high DPP4 expression and defining optimal seeding density and protein binding conditions. The ability of monoclonal antibodies to inhibit MERS-CoV S binding was then tested. Binding inhibition results were comparable with those described in previous literature for MERS-CoV spike monomer and showed similar patterns as neutralization results. The coefficient of variation (CV) of our cell-based assay was <10%. The proposed image cytometry method provides an efficient approach for characterizing potential therapeutic antibodies for combating MERS-CoV that compares favorably with current methods. The ability to rapidly determine direct antibody binding to host cells in a high-throughput manner can be applied to study other pathogen-antibody interactions and thus can impact future research on viral pathogens.",,"['Rosen, Osnat', 'Chan, Leo Li-Ying', 'Abiona, Olubukola', 'Gough, Portia', 'Wang, Lingshu', 'Shi, Wei', 'Zhang, Yi', 'Wang, Nianshuang', 'Kong, Wing-Pui', 'McLellan, Jason S.', 'Graham, Barney S.', 'Corbett, Kizzmekia S.']",,,,
,PMC,Interferon regulatory factors 3 and 7 have distinct roles in the pathogenesis of alphavirus encephalomyelitis,http://dx.doi.org/10.1099/jgv.0.001174,PMC7011693,,,"Interferon (IFN) regulatory factors (IRFs) are important determinants of the innate response to infection. We evaluated the role(s) of combined and individual IRF deficiencies in the outcome of infection of C57BL/6 mice with Sindbis virus, an alphavirus that infects neurons and causes encephalomyelitis. The brain and spinal cord levels of Irf7, but not Irf3 mRNAs, were increased after infection. IRF3/5/7−/− and IRF3/7−/− mice died within 3–4 days with uncontrolled virus replication, similar to IFNα receptor-deficient mice, while all wild-type (WT) mice recovered. IRF3−/− and IRF7−/− mice had brain levels of IFNα that were lower, but brain and spinal cord levels of IFNβ and IFN-stimulated gene mRNAs that were similar to or higher than WT mice without detectable serum IFN or increases in Ifna or Ifnb mRNAs in the lymph nodes, indicating that the differences in outcome were not due to deficiencies in the central nervous system (CNS) type I IFN response. IRF3−/− mice developed persistent neurological deficits and had more spinal cord inflammation and higher CNS levels of Il1b and Ifnγ mRNAs than WT mice, but all mice survived. IRF7−/− mice died 5–8 days after infection with rapidly progressive paralysis and differed from both WT and IRF3−/− mice in the induction of higher CNS levels of IFNβ, tumour necrosis factor (TNF) α and Cxcl13 mRNA, delayed virus clearance and more extensive cell death. Therefore, fatal disease in IRF7−/− mice is likely due to immune-mediated neurotoxicity associated with failure to regulate the production of inflammatory cytokines such as TNFα in the CNS.",,"['Schultz, Kimberly L. W.', 'Troisi, Elizabeth M.', 'Baxter, Victoria K.', 'Glowinski, Rebecca', 'Griffin, Diane E.']",,,,
,PMC,Infection prevention and control in paediatric office settings,http://dx.doi.org/10.1093/pch/pxy117,PMC6242053,,,"Transmission of infection in the paediatric office is an issue of increasing concern. This document discusses routes of transmission of infection and the principles of current infection control measures. Prevention includes appropriate office design and administrative policies, triage, routine practices for the care of all patients (e.g., hand hygiene; use of gloves, masks, eye protection, and gowns for specific procedures; adequate cleaning, disinfection, and sterilization of surfaces and equipment, including toys; and aseptic technique for invasive procedures), and additional precautions for specific infections. Personnel should be adequately immunized, and those infected should follow work-restriction policies.",,"Moore, Dorothy L",,,,
,PMC,La prévention et le contrôle des infections au cabinet du pédiatre,http://dx.doi.org/10.1093/pch/pxy118,PMC6241950,,,"La transmission d’infections au cabinet du pédiatre est une source de préoccupation croissante. Le présent document traite des voies de transmission des infections et des principes de contrôle des infections actuellement en vigueur. La prévention englobe un aménagement du cabinet et des politiques administratives appropriés, le triage, les pratiques de soins habituelles pour tous les patients (p. ex., hygiène des mains; port de gants, de masques, d’un dispositif de protection oculaire et de blouses pour certaines interventions; nettoyage, désinfection et stérilisation des surfaces et de l’équipement, y compris les jouets; technique d’asepsie pour les interventions invasives), ainsi que les précautions additionnelles en cas d’infections particulières. Les membres du personnel doivent avoir reçu les vaccins nécessaires, et ceux qui sont atteints d’une infection doivent respecter les politiques de restriction au travail.",,"Moore, Dorothy L",,,,
,PMC,Infection and propagation of astrovirus VA1 in cell culture,http://dx.doi.org/10.1002/cpmc.73,PMC6340763,,,"Astrovirus VA1/HMO-C (VA1) is the representative genotype of mamastrovirus 9, a species of the single stranded, positive-sense RNA viral family, Astroviridae. Astroviruses have been traditionally considered pathogens of the gastrointestinal tract, but they have been recently associated with neurological diseases in humans, cattle, mink, sheep, and pigs. VA1 is the astrovirus genotype most commonly identified from human cases of meningoencephalitis and has been recently propagated in cell culture. VA1 can now be used as a model system to study pathogenesis of the neurological diseases associated with astrovirus infection. In this unit, we describe two fundamental assays to quantify replication and propagation of VA1, a qRT-PCR to measure viral RNA and a TCID(50) assay to measure infectious viral particles.",,"['Janowski, Andrew B', 'Wang, David']",,,,
,PMC,Chronic Airway Colonization by Achromobacter xylosoxidans in Cystic Fibrosis Patients Is Not Sustained by Their Domestic Environment,http://dx.doi.org/10.1128/AEM.01739-18,PMC6238067,,,"Achromobacter spp. are nonfermentative Gram-negative bacilli considered emergent pathogens in cystic fibrosis (CF). Although some cross-transmission events between CF patients have been described, Achromobacter strains were mostly patient specific, suggesting sporadic acquisitions from nonhuman reservoirs. However, sources of these emergent CF pathogens remain unknown. A large collection of specimens (n = 273) was sampled in the homes of 3 CF patients chronically colonized by Achromobacter xylosoxidans with the aim of evaluating the potential role of domestic reservoirs in sustaining airway colonization of the patients. Samples were screened for the presence of Achromobacter by using genus-specific molecular detection. Species identification, multilocus genotypes, and antimicrobial susceptibility patterns observed for environmental isolates were compared with those of clinical strains. Patient homes hosted a high diversity of Achromobacter species (n = 7), including Achromobacter mucicolens and A. animicus, two species previously isolated from human samples only, and genotypes (n = 15), all showing an overall susceptibility to antimicrobial agents. Achromobacter strains were mostly isolated from indoor moist environments and siphons, which are potential reservoirs for several CF emerging pathogens. A. xylosoxidans, the worldwide prevalent species colonizing CF patients, was not the major Achromobacter species inhabiting domestic environments. A. xylosoxidans genotypes chronically colonizing the patients were not detected in their household environments. These results support the notions that the domestic environment could not be incriminated in sustained patient colonization and that after initial colonization, the environmental survival of A. xylosoxidans clones adapted to the CF airways is probably impaired. IMPORTANCE Achromobacter spp. are worldwide emerging opportunistic pathogens in CF patients, able to chronically colonize the respiratory tract. Apart from regular consultations at the hospital CF center, patients spend most of their time at home. Colonization from nonhuman sources has been suggested, but the presence of Achromobacter spp. in CF patients' homes has not been explored. The domestic environments of CF patients chronically colonized by Achromobacter, especially wet environments, host several opportunistic pathogens, including a large diversity of Achromobacter species and genotypes. However, Achromobacter genotypes colonizing the patients were not detected in their domestic environments, making it unlikely that a shuttle between environment and CF airways is involved in persisting colonization. This also suggests that once the bacteria have adapted to the respiratory tract, their survival in the domestic environment is presumably impaired. Nevertheless, measures for reducing domestic patient exposure should be targeted on evacuation drains, which are frequently contaminated by CF opportunistic pathogens.",,"['Dupont, Chloé', 'Jumas-Bilak, Estelle', 'Doisy, Clara', 'Aujoulat, Fabien', 'Chiron, Raphaël', 'Marchandin, Hélène']",,,,
,PMC,Bioaerosol Sampler Choice Should Consider Efficiency and Ability of Samplers To Cover Microbial Diversity,http://dx.doi.org/10.1128/AEM.01589-18,PMC6238049,,,"Bioaerosol studies aim to describe the microbial content and increase understanding of the aerosolization processes linked to diseases. Air samplers are used to collect, identify, and quantify bioaerosols. Studies comparing the performances of air samplers have typically used a culture approach or have targeted a specific microorganism in laboratory settings. The objective of this study was to use environmental field samples to compare the efficiencies of 3 high-airflow-rate samplers for describing bioaerosol diversity using a next-generation sequencing approach. Two liquid cyclonic impactors and one electrostatic filter dry sampler were used in four wastewater treatment plants to target bacterial diversity and in five dairy farms to target fungal diversity. The dry electrostatic sampler was consistently more powerful in collecting more fungal and bacterial operational taxonomic units (OTUs). Substantial differences in OTU abundances between liquid and dry sampling were revealed. The majority of the diversity revealed by dry electrostatic sampling was not identified using the cyclonic liquid impactors. The findings from this work suggest that the choice of a bioaerosol sampler should include information about the efficiency and ability of samplers to cover microbial diversity. Although these results suggest that electrostatic filters result in better coverage of the microbial diversity among the tested air samplers, further studies are needed to confirm this hypothesis. While it is difficult to determine a single universally optimal air sampler, this work provides an in-depth look at some of the considerations that are essential when choosing an air sampler for studying the microbial ecology of bioaerosols. IMPORTANCE Associating bioaerosol exposure and health problems is challenging, and adequate exposure monitoring is a priority for scientists in the field. Conclusions that can be drawn from bioaerosol exposure studies are highly dependent on the design of the study and the methodologies used. The air sampling strategy is the first methodological step leading to an accurate interpretation of what is present in the air. Applying new molecular approaches to evaluate the efficiencies of the different types of samplers used in the field is necessary in order to circumvent traditional approaches and the biases they introduce to such studies. The results and conclusions provided in this paper should be taken in consideration when conducting a bioaerosol study.",,"['Mbareche, Hamza', 'Veillette, Marc', 'Bilodeau, Guillaume J.', 'Duchaine, Caroline']",,,,
,PMC,Development of Novel DNA-Encoded PCSK9 Monoclonal Antibodies as Lipid-Lowering Therapeutics,http://dx.doi.org/10.1016/j.ymthe.2018.10.016,PMC6319316,,,"Elevated low-density lipoprotein cholesterol (LDL-C) is one of the major contributors to cardiovascular heart disease (CHD), the leading cause of death worldwide. Due to severe side effects of statins, alternative treatment strategies are required for statin-intolerant patients. Monoclonal antibodies (mAbs) targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) have shown great efficacy in LDL-C reduction. Limitations for this approach include the need for multiple injections as well as increased costs associated with patient management. Here, we engineered a DNA-encoded mAb (DMAb) targeting PCSK9 (daPCSK9), as an alternative approach to protein-based lipid-lowering therapeutics, and we characterized its expression and activity. A single intramuscular administration of mouse daPCSK9 generated expression in vivo for over 42 days that corresponded with a substantial decrease of 28.6% in non-high-density lipoprotein cholesterol (non-HDL-C) and 10.3% in total cholesterol by day 7 in wild-type mice. Repeated administrations of the DMAb plasmid led to increasing expression, with DMAb levels of 7.5 μg/mL at day 62. daPCSK9 therapeutics may provide a novel, simple, less frequent, cost-effective approach to reducing LDL-C, either as a stand-alone therapy or in combination with other LDL-lowering therapeutics for synergistic effect.",,"['Khoshnejad, Makan', 'Patel, Ami', 'Wojtak, Krzysztof', 'Kudchodkar, Sagar B.', 'Humeau, Laurent', 'Lyssenko, Nicholas N.', 'Rader, Daniel J.', 'Muthumani, Kar', 'Weiner, David B.']",,,,
,PMC,Global Health Security: Protecting the United States in an Interconnected World,http://dx.doi.org/10.1177/0033354918808313,PMC6304723,,,,,"['Bunnell, Rebecca E.', 'Ahmed, Zara', 'Ramsden, Megan', 'Rapposelli, Karina', 'Walter-Garcia, Madison', 'Sharmin, Eshita', 'Knight, Nancy']",,,,
,PMC,APOBEC3H Subcellular Localization Determinants Define Zipcode for Targeting HIV-1 for Restriction,http://dx.doi.org/10.1128/MCB.00356-18,PMC6234287,,,"APOBEC enzymes are DNA cytosine deaminases that normally serve as virus restriction factors, but several members, including APOBEC3H, also contribute to cancer mutagenesis. Despite their importance in multiple fields, little is known about cellular processes that regulate these DNA mutating enzymes. We show that APOBEC3H exists in two distinct subcellular compartments, cytoplasm and nucleolus, and that the structural determinants for each mechanism are genetically separable. First, native and fluorescently tagged APOBEC3Hs localize to these two compartments in multiple cell types. Second, a series of genetic, pharmacologic, and cell biological studies demonstrate active cytoplasmic and nucleolar retention mechanisms, whereas nuclear import and export occur through passive diffusion. Third, APOBEC3H cytoplasmic retention determinants relocalize APOBEC3A from a passive cell-wide state to the cytosol and, additionally, endow potent HIV-1 restriction activity. These results indicate that APOBEC3H has a structural zipcode for subcellular localization and selecting viral substrates for restriction.",,"['Salamango, Daniel J.', 'Becker, Jordan T.', 'McCann, Jennifer L.', 'Cheng, Adam Z.', 'Demir, Özlem', 'Amaro, Rommie E.', 'Brown, William L.', 'Shaban, Nadine M.', 'Harris, Reuben S.']",,,,
,PMC,"Interplay between the Poly(A) Tail, Poly(A)-Binding Protein, and Coronavirus Nucleocapsid Protein Regulates Gene Expression of Coronavirus and the Host Cell",http://dx.doi.org/10.1128/JVI.01162-18,PMC6232474,,,"In the present study, we investigated the roles of interactions among the poly(A) tail, coronavirus nucleocapsid (N) protein, and poly(A)-binding protein (PABP) in the regulation of coronavirus gene expression. Through dissociation constant (K(d)) comparison, we found that the coronavirus N protein can bind to the poly(A) tail with high affinity, establishing N protein as a PABP. A subsequent analysis with UV cross-linking and immunoprecipitation revealed that the N protein is able to bind to the poly(A) tail in infected cells. Further examination demonstrated that poly(A) tail binding by the N protein negatively regulates translation of coronaviral RNA and host mRNA both in vitro and in cells. Although the N protein can interact with PABP and eukaryotic initiation factor 4G (eIF4G), the poor interaction efficiency between the poly(A)-bound N protein and eIF4E may explain the observed decreased translation efficiency. In addition to interaction with translation factor eIF4G, the N protein is able to interact with coronavirus nonstructural protein 9 (nsp9), a replicase protein required for replication. The study demonstrates interactions among the poly(A) tail, N protein, and PABP both in vitro and in infected cells. Of the interactions, binding of the poly(A) tail to N protein decreases the interaction efficiency between the poly(A) tail and eIF4E, leading to translation inhibition. The poly(A)-dependent translation inhibition by N protein has not been previously demonstrated and thus extends our understanding of coronavirus gene expression. IMPORTANCE Gene expression in coronavirus is a complicated and dynamic process. In this study, we demonstrated that coronavirus N protein is able to bind to the poly(A) tail with high affinity, establishing N protein as a PABP. We also show how the interplay between coronavirus 3′ poly(A) tail, PABP, and N protein regulates gene expression of the coronavirus and host cell. Of the interactions, poly(A) tail binding by the N protein negatively regulates translation, and to our knowledge, this inhibition of translation by binding of the N protein to poly(A) tail has not been previously studied. Accordingly, the study provides fundamental molecular details regarding coronavirus infection and expands our knowledge of coronavirus gene expression.",,"['Tsai, Tsung-Lin', 'Lin, Ching-Houng', 'Lin, Chao-Nan', 'Lo, Chen-Yu', 'Wu, Hung-Yi']",,,,
,PMC,Molecular Characterization of the Viroporin Function of Foot-and-Mouth Disease Virus Nonstructural Protein 2B,http://dx.doi.org/10.1128/JVI.01360-18,PMC6232471,,,"Nonstructural protein 2B of foot-and-mouth disease (FMD) virus (FMDV) is comprised of a small, hydrophobic, 154-amino-acid protein. Structure-function analyses demonstrated that FMDV 2B is an ion channel-forming protein. Infrared spectroscopy measurements using partially overlapping peptides that spanned regions between amino acids 28 and 147 demonstrated the adoption of helical conformations in two putative transmembrane regions between residues 60 and 78 and between residues 119 and 147 and a third transmembrane region between residues 79 and 106, adopting a mainly extended structure. Using synthetic peptides, ion channel activity measurements in planar lipid bilayers and imaging of single giant unilamellar vesicles (GUVs) revealed the existence of two sequences endowed with membrane-porating activity: one spanning FMDV 2B residues 55 to 82 and the other spanning the C-terminal region of 2B from residues 99 to 147. Mapping the latter sequence identified residues 119 to 147 as being responsible for the activity. Experiments to assess the degree of insertion of the synthetic peptides in bilayers and the inclination angle adopted by each peptide regarding the membrane plane normal confirm that residues 55 to 82 and 119 to 147 of 2B actively insert as transmembrane helices. Using reverse genetics, a panel of 13 FMD recombinant mutant viruses was designed, which harbored nonconservative as well as alanine substitutions in critical amino acid residues in the area between amino acid residues 28 and 147. Alterations to any of these structures interfered with pore channel activity and the capacity of the protein to permeabilize the endoplasmic reticulum (ER) to calcium and were lethal for virus replication. Thus, FMDV 2B emerges as the first member of the viroporin family containing two distinct pore domains. IMPORTANCE FMDV nonstructural protein 2B is able to insert itself into cellular membranes to form a pore. This pore allows the passage of ions and small molecules through the membrane. In this study, we were able to show that both current and small molecules are able to pass though the pore made by 2B. We also discovered for the first time a virus with a pore-forming protein that contains two independent functional pores. By making mutations in our infectious clone of FMDV, we determined that mutations in either pore resulted in nonviable virus. This suggests that both pore-forming functions are independently required during FMDV infection.",,"['Gladue, D. P.', 'Largo, E.', 'de la Arada, I.', 'Aguilella, V. M.', 'Alcaraz, A.', 'Arrondo, J. L. R.', 'Holinka, L. G.', 'Brocchi, E.', 'Ramirez-Medina, E.', 'Vuono, E. A.', 'Berggren, K. A.', 'Carrillo, C.', 'Nieva, J. L.', 'Borca, M. V.']",,,,
,PMC,Attenuation of Influenza A Virus Disease Severity by Viral Coinfection in a Mouse Model,http://dx.doi.org/10.1128/JVI.00881-18,PMC6232468,,,"Influenza viruses and rhinoviruses are responsible for a large number of acute respiratory viral infections in human populations and are detected as copathogens within hosts. Clinical and epidemiological studies suggest that coinfection by rhinovirus and influenza virus may reduce disease severity and that they may also interfere with each other’s spread within a host population. To determine how coinfection by these two unrelated respiratory viruses affects pathogenesis, we established a mouse model using a minor serogroup rhinovirus (rhinovirus strain 1B [RV1B]) and mouse-adapted influenza A virus (A/Puerto Rico/8/1934 [PR8]). Infection of mice with RV1B 2 days before PR8 reduced the severity of infection by a low or medium, but not high, dose of PR8. Disease attenuation was associated with an early inflammatory response in the lungs and enhanced clearance of PR8. However, coinfection by RV1B did not reduce PR8 viral loads early in infection or inhibit replication of PR8 within respiratory epithelia or in vitro. Inflammation in coinfected mice remained focal compared to diffuse inflammation and damage in the lungs of mice infected by PR8. The timing of RV1B coinfection was a critical determinant of protection, suggesting that sufficient time is needed to induce this response. Finally, disease attenuation was not unique to RV1B: dose-dependent coinfection by a murine coronavirus (mouse hepatitis virus strain 1 [MHV-1]) also reduced the severity of PR8 infection. Unlike RV1B, coinfection with MHV-1 reduced early PR8 replication, which was associated with upregulation of beta interferon (IFN-β) expression. This model is critical for understanding the mechanisms responsible for influenza disease attenuation during coinfection by unrelated respiratory viruses. IMPORTANCE Viral infections in the respiratory tract can cause severe disease and are responsible for a majority of pediatric hospitalizations. Molecular diagnostics have revealed that approximately 20% of these patients are infected by more than one unrelated viral pathogen. To understand how viral coinfection affects disease severity, we inoculated mice with a mild viral pathogen (rhinovirus or murine coronavirus), followed 2 days later by a virulent viral pathogen (influenza A virus). This model demonstrated that rhinovirus can reduce the severity of influenza A virus, which corresponded with an early but controlled inflammatory response in the lungs and early clearance of influenza A virus. We further determined the dose and timing parameters that were important for effective disease attenuation and showed that influenza disease is also reduced by coinfection with a murine coronavirus. These findings demonstrate that coinfecting viruses can alter immune responses and pathogenesis in the respiratory tract.",,"['Gonzalez, Andres J.', 'Ijezie, Emmanuel C.', 'Balemba, Onesmo B.', 'Miura, Tanya A.']",,,,
,PMC,A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles,http://dx.doi.org/10.1074/jbc.RA118.005015,PMC6322876,,,"Viral infections still threaten human health all over the world, and many people die from viral diseases every year. However, there are no effective vaccines or drugs for preventing or managing most viral diseases. Thus, the discovery and development of broad-spectrum antiviral agents remain urgent. Here, we expressed and purified a venom peptide, Ev37, from the scorpion Euscorpiops validus in a prokaryotic system. We found that rEv37 can inhibit dengue virus type 2 (DENV-2), hepatitis C virus (HCV), Zika virus (ZIKV), and herpes simplex virus type 1 (HSV-1) infections in a dose-dependent manner at noncytotoxic concentrations, but that it has no effect on Sendai virus (SeV) and adenovirus (AdV) infections in vitro. Furthermore, rEv37 alkalized acidic organelles to prevent low pH–dependent fusion of the viral membrane–endosomal membrane, which mainly blocks the release of the viral genome from the endosome to the cytoplasm and then restricts viral late entry. Taken together, our results indicate that the scorpion venom peptide Ev37 is a broad-spectrum antiviral agent with a specific molecular mechanism against viruses undergoing low pH–dependent fusion activation during entry into host cells. We conclude that Ev37 is a potential candidate for development as an antiviral drug.",,"['Li, Fangfang', 'Lang, Yange', 'Ji, Zhenglin', 'Xia, Zhiqiang', 'Han, Yuewen', 'Cheng, Yuting', 'Liu, Gaomin', 'Sun, Fang', 'Zhao, Yonghui', 'Gao, Minjun', 'Chen, Zongyun', 'Wu, Yingliang', 'Li, Wenxin', 'Cao, Zhijian']",,,,
,PMC,Predicting Reservoir Hosts and Arthropod Vectors from Evolutionary Signatures in RNA Virus Genomes,http://dx.doi.org/10.1126/science.aap9072,PMC6536379,,,"Identifying the animal origins of RNA viruses requires years of field and laboratory studies that stall responses to emerging infectious diseases. Using large genomic and ecological datasets, we demonstrate that the animal reservoirs and the existence and identity of arthropod vectors can be predicted directly from viral genome sequences using machine learning. We illustrate the ability of these models to predict the epidemiology of diverse viruses across most human-infective families of single-stranded RNA viruses, including 69 viruses with previously elusive or never-investigated reservoirs or vectors. Models such as these, which capitalize on the proliferation of low-cost genomic sequencing, can narrow the time lag between virus discovery and targeted research, surveillance and management.",,"['Babayan, Simon A.', 'Orton, Richard J.', 'Streicker, Daniel G.']",,,,
,PMC,Better Prepare Than React: Reordering Public Health Priorities 100 Years After the Spanish Flu Epidemic,http://dx.doi.org/10.2105/AJPH.2018.304682,PMC6187800,,,"This commentary argues that 100 years after the deadly Spanish flu, the public health emergency community’s responses to much more limited pandemics and outbreaks demonstrate a critical shortage of personnel and resources. Rather than relying on nonpharmaceutical interventions, such as quarantine, the United States must reorder its health priorities to ensure adequate preparation for a large-scale pandemic.",,"Greenberger, Michael",,,,
,PMC,The Mother of All Pandemics Is 100 Years Old (and Going Strong)!,http://dx.doi.org/10.2105/AJPH.2018.304631,PMC6187799,,,"This year marks the 100th anniversary of the deadliest event in human history. In 1918–1919, pandemic influenza appeared nearly simultaneously around the globe and caused extraordinary mortality (an estimated 50–100 million deaths) associated with unexpected clinical and epidemiological features. The descendants of the 1918 virus remain today; as endemic influenza viruses, they cause significant mortality each year. Although the ability to predict influenza pandemics remains no better than it was a century ago, numerous scientific advances provide an important head start in limiting severe disease and death from both current and future influenza viruses: identification and substantial characterization of the natural history and pathogenesis of the 1918 causative virus itself, as well as hundreds of its viral descendants; development of moderately effective vaccines; improved diagnosis and treatment of influenza-associated pneumonia; and effective prevention and control measures. Remaining challenges include development of vaccines eliciting significantly broader protection (against antigenically different influenza viruses) that can prevent or significantly downregulate viral replication; more complete characterization of natural history and pathogenesis emphasizing the protective role of mucosal immunity; and biomarkers of impending influenza-associated pneumonia.",,"['Morens, David M.', 'Taubenberger, Jeffery K.']",,,,
,PMC,"Mucociliary Defense: Emerging Cellular, Molecular, and Animal Models",http://dx.doi.org/10.1513/AnnalsATS.201806-439AW,PMC6322027,,,"Respiratory tissues are bombarded by billions of particles daily. If allowed to accumulate, these particles can cause injury, inflammation, or infection, and thus may significantly disrupt airflow and gas exchange. Mucociliary defense, a primary mechanism for protecting host tissues, operates through the coordinated functions of mucus and cilia that trap and eliminate inhaled materials. Mucociliary function is also required for the elimination of endogenous cells and debris. Although defense is necessarily robust, it is also tightly regulated to minimize physiologic disruption of the host. Indeed, mucociliary dysfunction contributes to the pathogenesis of many lung diseases—including asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and cystic fibrosis—in which airflow limitation, inflammation, persistent tissue injury, and structural remodeling occur. Here, we highlight recent advances in cilia and mucin biology, the importance of well-controlled mucociliary interactions, and the need to better understand how these regulate innate barrier and immune defense.",,"['Benam, Kambez H.', 'Vladar, Eszter K.', 'Janssen, William J.', 'Evans, Christopher M.']",,,,
,PMC,The National Advisory Committee on Infection Prevention and Control (NAC-IPC),http://dx.doi.org/10.14745/ccdr.v44i11a03,PMC6449104,,,"This paper describes the work of the National Advisory Committee on Infection Prevention and Control (NAC-IPC), previously Infection Prevention and Control Expert Working Group, a longstanding external advisory body that provides subject matter expertise and advice to the Public Health Agency of Canada (PHAC) on the prevention and control of infectious diseases in Canadian health care settings. Originally established by Health Canada as the Infection Control Guidelines Steering Committee in 1992, this advisory board has been providing expert advice on infection prevention and control (IPC) guideline development for over 25 years. The NAC-IPC provides advice to inform the development of comprehensive or concise guidelines, quick reference guides and interim guidelines (usually for emerging pathogens), working closely with PHAC’s national Healthcare-Associated Infections (HAIs) surveillance programs for Canadian health care facilities. PHAC’s HAI-IPC professionals conduct the necessary literature research, data extraction, evidence synthesis, evidence grading (where applicable) and scientific writing for the guidelines. Due to the paucity of clinical trials and high quality observational studies to inform recommendations for emerging pathogens, expert opinion is critical for interpreting available evidence. .",,"['Ogunremi, T', 'Dunn, K', 'Johnston, L', 'Embree, J']",,,,
,PMC,Propofol infusion-like syndrome in a dog,,PMC6190180,,,"An 8-year-old, spayed female Chihuahua mixed breed dog was presented for dyspnea and was subsequently mechanically ventilated. Propofol was utilized as part of the anesthetic protocol. The dog developed rhabdomyolysis, myoglobinuria, cardiac arrhythmias, liver enzyme elevation, and methemoglobinemia. Propofol was discontinued and N-acetylcysteine was administered after which the clinical signs resolved.",,"['Mallard, John M.', 'Rieser, Teresa M.', 'Peterson, Nathan W.']",,,,
,PMC,Persistence of systemic murine norovirus is maintained by inflammatory recruitment of susceptible myeloid cells,http://dx.doi.org/10.1016/j.chom.2018.10.003,PMC6248887,,,"Viral persistence can contribute to chronic disease and promote virus dissemination. Prior work demonstrated that timely clearance of systemic murine norovirus (MNV) infection depends on cell-intrinsic type I interferon responses and adaptive immunity. We now find that the capsid of the systemically replicating MNV strain CW3 promotes lytic cell death, release of IL-1α, and increased inflammatory cytokine release. Correspondingly, inflammatory monocytes and neutrophils are recruited to sites of infection in a CW3 capsid-dependent manner. Recruited monocytes and neutrophils are subsequently infected, representing a majority of infected cells in vivo. Systemic depletion of inflammatory monocytes or neutrophils from persistently infected Rag1(−/−) mice reduces viral titers in a tissue-specific manner. These data indicate that the CW3 capsid facilitates lytic cell death, inflammation, and recruitment of susceptible cells to promote persistence. Infection of continuously recruited inflammatory cells may be a mechanism of persistence broadly utilized by lytic viruses incapable of establishing latency.",,"['Van Winkle, Jacob A.', 'Robinson, Bridget A.', 'Peters, A. Mack', 'Li, Lena', 'Nouboussi, Ruth V.', 'Mack, Matthias', 'Nice, Timothy J.']",,,,
,PMC,Home Cage Compared with Induction Chamber for Euthanasia of Laboratory Rats,http://dx.doi.org/10.30802/AALAS-JAALAS-17-000160,PMC6241385,,,"This study compared behavioral and physiologic changes in Sprague–Dawley and Brown Norway rats that were euthanized by using a 30% volume displacement rate of CO(2) in either their home cage or an induction chamber; rats euthanized in the home cage were hypothesized to demonstrate a higher level of animal wellbeing. No significant differences were detected in the physiologic responses to home cage versus induction chamber euthanasia groups. A few strain-related behavioral differences occurred. The number of digs per second was higher in Brown Norway compared with Sprague–Dawley rats when in the home cage, where a digging substrate was present. Rearing frequency was higher in both Brown Norway and Sprague–Dawley rats in the induction chamber compared with the home cage. This study demonstrated that although strain-specific differences were associated with the process of euthanasia, there were no significant differences between the treatment groups of home cage compared with induction chamber. This finding suggests that—from the perspective of a rat—either the home cage or an induction chamber can be used for euthanasia, with likely extension of this conclusion to use of either method to the induction of anesthesia.",,"Hickman, Debra L",,,,
,PMC,"Interpreting Neuroendocrine Hormones, Corticosterone, and Blood Glucose to Assess the Wellbeing of Anesthetized Rats during Euthanasia",http://dx.doi.org/10.30802/AALAS-JAALAS-17-000159,PMC6241377,,,"Current recommendations for assessing animal wellbeing during euthanasia suggest that measuring neuroendocrine hormones—such as ACTH, noradrenaline, and adrenaline—is preferable to measuring corticosterone and blood glucose because of the sensitivity of neuroendocrine hormones to the acute stress associated with rapid methods of euthanasia. However, these neuroendocrine hormones can be stimulated in ways that confound interpretation of welfare assessment in euthanasia studies. Although this property does not negate the usefulness of neuroendocrine hormones as tools of assessment, it is important to differentiate the stress associated with the induction of anesthesia before the loss of consciousness (an animal wellbeing concern) with the physiologic responses that occur after the loss of consciousness (not an animal wellbeing concern). In this study, rats were anesthetized by using a ketamine–xylazine combination. Once the rats achieved a surgical plane of anesthesia, they were exposed to O(2), CO(2), or isoflurane, followed by terminal blood collection to assess concentrations of ACTH, noradrenaline, corticosterone, and blood glucose. Compared with animals exposed to O(2) or isoflurane, rats exposed to CO(2) had significant increases in their serum concentrations of ACTH and noradrenaline, but blood glucose and corticosterone did not differ between groups. These findings indicate that noradrenaline and ACTH should be used with caution to assess animal wellbeing when the method of euthanasia might confound that assessment.",,"Hickman, Debra L",,,,
,PMC,Association of Procalcitonin Value and Bacterial Coinfections in Pediatric Patients With Viral Lower Respiratory Tract Infections Admitted to the Pediatric Intensive Care Unit,http://dx.doi.org/10.5863/1551-6776-23.6.466,PMC6336174,,,"OBJECTIVE: Our primary objective was to determine the utility of procalcitonin (PCT) in detection of bacterial coinfection in children < 5 years admitted to the pediatric intensive care unit with viral lower respiratory tract infection (LRTI). METHODS: Electronic medical record review of children < 5 years admitted to the pediatric intensive care unit with a viral LRTI who also had at least 1 PCT concentration measurement. RESULTS: Seventy-five patients were admitted to the intensive care unit and met the inclusion criteria for this investigation. The PCT threshold concentrations of 0.9, 1, 1.4, and 2 ng/mL were found to be statistically significant in determining the presence of a bacterial coinfection. The PCT concentration with the most utility was 1.4 ng/mL with sensitivity, specificity, positive and negative predictive values of 46%, 83%, 68%, and 76%, respectively. For patients with serial PCTs, the second PCT correctly influenced treatment decisions for 11 of 25 patients (44%). CONCLUSIONS: A PCT value of 1.4 ng/mL determined the presence of a bacterial coinfection primarily owing to the high specificity and negative predictive value. Our data add evidence to the relatively high negative predictive value of PCT concentrations in identifying patients with bacterial coinfection, specifically in the case of viral LRTI. In addition, our preliminary data indicate serial PCT measurements may help further influence correct treatment decisions. Prospective, controlled studies are warranted to validate an appropriate PCT threshold concentration to help in identifying bacterial coinfection as well as to further explore the role of serial PCT values in determining the absence or presence of a bacterial coinfection.",,"['Kotula, John J.', 'Moore, Wayne S.', 'Chopra, Arun', 'Cies, Jeffrey J.']",,,,
,PMC,Clinical features of Mycoplasma pneumoniae coinfection and need for its testing in influenza pneumonia patients,http://dx.doi.org/10.21037/jtd.2018.10.33,PMC6297417,,,"BACKGROUND: To investigate the clinical features of coinfection due to Mycoplasma pneumoniae (M. pneumoniae), a common copathogen in influenza, in influenza pneumonia patients. METHODS: We reviewed 4,465 patients with influenza who visited a tertiary care hospital emergency department in Seoul (Korea) from 2010 through 2016, and underwent immunoglobulin M (IgM) serology or polymerase chain reaction (PCR) for M. pneumoniae. Influenza pneumonia was defined as laboratory-confirmed influenza plus radiographic pneumonia. Patients with healthcare-associated pneumonia or non-mycoplasma bacterial coinfection were excluded. Clinical, laboratory, and radiographic findings and outcomes of the influenza pneumonia patients with and without M. pneumoniae coinfection were compared. Multivariable logistic regression analysis was performed to identify factors associated with the coinfection. RESULTS: Of 244 influenza pneumonia patients, 41 (16.8%) had M. pneumoniae coinfection. These patients were younger with a higher frequency of age of 5–10 years, and had higher white blood cell (WBC) and lymphocyte counts; lower concentration of C-reactive protein (CRP). The coinfection had no association with specific radiographic findings and poor outcome. Multivariable analysis showed the age of 5–10 years (adjusted odds ratio, 18.83; 95% confidence interval, 5.899–60.08; P<0.001) as the factor associated with the coinfection. CONCLUSIONS: M. pneumoniae coinfection in influenza pneumonia may be associated with the age of 5–10 years, and otherwise clinically indistinct from influenza pneumonia without the coinfection. This finding suggests the need for M. pneumoniae testing in patients aged 5–10 years with influenza pneumonia.",,"['Kim, Jung Heon', 'Kwon, Jae Hyun', 'Lee, Jeong-Yong', 'Lee, Jong Seung', 'Ryu, Jeong-Min', 'Kim, Sung-Han', 'Lim, Kyoung Soo', 'Kim, Won Young']",,,,
,PMC,Distribution of the atypical pathogens of community-acquired pneumonia to disease severity,http://dx.doi.org/10.21037/jtd.2018.10.50,PMC6297405,,,"BACKGROUND: To investigate the epidemiological characteristics of 11 atypical pathogens of community-acquired pneumonia (CAP) among Chinese, and to determine whether or not there is an association between these pathogens and the severity of illness. METHODS: We conducted a surveillance study for CAP in 30 hospitals of Beijing. Epidemiological data and clinical specimens were systematically collected from enrolled CAP patients. The detection for 11 atypical pathogens [9 respiratory viruses, Mycoplasma pneumoniae (MP) and Chlamydophila pneumoniae (CP)] was performed. Risk factors of severe CAP and death in Hospital were evaluated. RESULTS: A total of 6,008 CAP patients [including 1,071 severe CAP (SCAP)] were enrolled. The overall detection rate of the 11 atypical pathogens was 42.4% among 1,925 child CAP (39.9% among 274 child SCAP), and 25.8% among 4,083 adult CAP (22.8% among 797 adult SCAP). The most frequent atypical pathogen among child SCAP was parainfluenza virus (10.2%) followed by respiratory syncytial virus (RSV) (8.4%). However, the most frequent atypical pathogen among adult SCAP was influenza virus (8.9%) followed by parainfluenza virus (3.8%). Multivariate analyses showed that the important predictors for SCAP were an age ≤9 years, an age ≥65 years and co-existing diseases. These factors, except an age ≤9 years, were also predictors of death in Hospital. None of these 11 atypical pathogens was included as the risk factors of SCAP or death in Hospital. CONCLUSIONS: Although these 11 atypical pathogens were the common causes of CAP (including SCAP) among Chinese, they were not observed to increase risks for SCAP or death in Hospital.",,"['Gong, Cheng', 'Zhang, Tiegang', 'Luo, Ming', 'Li, Aihua', 'Dong, Mei', 'Li, Maozhong', 'Wang, Yiting', 'Huang, Fang']",,,,
,PMC,"The Tracheal Microbiota in Patients with a Tracheostomy Before, During, and After an Acute Respiratory Infection",http://dx.doi.org/10.1097/INF.0000000000001952,PMC6097614,,,"Examining tracheal microbiota before, during, and after acute respiratory infection (ARI) in patients with a tracheostomy demonstrated large baseline intra-patient microbiota variability and a significant bloom of Haemophilus and Moraxella on day 1 of ARI symptoms. The tracheal microbiota community composition changed significantly from baseline to 1 month after ARI.",,"['Pérez-Losada, Marcos', 'Graham, Robert J.', 'Coquillette, Madeline', 'Jafarey, Amenah', 'Castro-Nallar, Eduardo', 'Aira, Manuel', 'Hoptay, Claire', 'Freishtat, Robert J.', 'Mansbach, Jonathan M.']",,,,
,PMC,Impact of community respiratory viral infections in urban children with asthma,http://dx.doi.org/10.1016/j.anai.2018.10.021,PMC6360098,,,"BACKGROUND: Upper respiratory tract viral infections cause asthma exacerbations in children. However, the impact of natural colds on asthmatic children in the community, particularly in the high-risk urban environment, is less well-defined. OBJECTIVE: We hypothesized that children with high-symptom upper respiratory viral infections have reduced airway function and greater respiratory tract inflammation than children with virus-positive low-symptom illnesses or virus-negative upper respiratory tract symptoms. METHODS: We studied 53 asthmatic children from Detroit, Michigan during scheduled surveillance periods and self-reported respiratory illnesses for one year. Symptom score, spirometry, fraction of exhaled nitric oxide (FeNO) and nasal aspirate biomarkers, viral nucleic acid and rhinovirus (RV) copy number were assessed. RESULTS: Of 658 aspirates collected, 22.9% of surveillance samples and 33.7% of respiratory illnesses were virus-positive. Compared to the virus-negative asymptomatic condition, children with severe colds (symptom score ≥5) showed reduced forced expiratory flow at 25–75% of the pulmonary volume (FEF25–75), higher nasal mRNA expression of C-X-C motif chemokine ligand (CXCL)-10 and melanoma differentiation-associated protein 5, and higher protein abundance of CXCL8, CXCL10 and C-C motif chemokine ligands (CCL)-2, CCL4, CCL20 and CCL24. Children with mild (symptom score 1–4) and asymptomatic infections showed normal airway function and fewer biomarker elevations. Virus-negative cold-like illnesses demonstrated increased FeNO, minimal biomarker elevation and normal airflow. RV copy number was associated with nasal chemokine levels but not symptom score. CONCLUSION: Urban asthmatic children with high-symptom respiratory viral infections have reduced FEF25–75 and more elevations of nasal biomarkers than children with mild or asymptomatic infections, or virus-negative illnesses.",,"['Lewis, Toby C.', 'Metitiri, Ediri E.', 'Mentz, Graciela B.', 'Ren, Xiaodan', 'Goldsmith, Adam M.', 'Eder, Breanna N.', 'Wicklund, Kyra E.', 'Walsh, Megan P.', 'Comstock, Adam T.', 'Ricci, Jeannette M.', 'Brennan, Sean R.', 'Washington, Ginger L.', 'Owens, Kendall B.', 'Mukherjee, Bhramar', 'Robins, Thomas G.', 'Batterman, Stuart A.', 'Hershenson, Marc B.', None]",,,,
,PMC,Heliox for croup in children,http://dx.doi.org/10.1002/14651858.CD006822.pub5,PMC6516979,,,"BACKGROUND: Croup is an acute viral respiratory infection with upper airway mucosal inflammation that may cause respiratory distress. Most cases are mild. Moderate to severe croup may require treatment with corticosteroids (from which benefits are often delayed) and nebulised epinephrine (adrenaline) (which may be short‐lived and can cause dose‐related adverse effects including tachycardia, arrhythmias, and hypertension). Rarely, croup results in respiratory failure necessitating emergency intubation and ventilation. A mixture of helium and oxygen (heliox) may prevent morbidity and mortality in ventilated neonates by reducing the viscosity of the inhaled air. It is currently used during emergency transport of children with severe croup. Anecdotal evidence suggests that it relieves respiratory distress. This review updates versions published in 2010 and 2013. OBJECTIVES: To examine the effect of heliox compared to oxygen or other active interventions, placebo, or no treatment, on relieving signs and symptoms in children with croup as determined by a croup score and rates of admission and intubation. SEARCH METHODS: We searched CENTRAL, which includes the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE; Embase; CINAHL; Web of Science; and LILACS in January and February 2018. We also searched the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/) and ClinicalTrials.gov (clinicaltrials.gov) on 8 February 2018. We contacted British Oxygen Company, a leading supplier of heliox (BOC Australia 2017). SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi‐RCTs comparing the effect of heliox in comparison with placebo or any active intervention(s) in children with croup. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We reported data that could not be pooled for statistical analysis descriptively. MAIN RESULTS: We included 3 RCTs with 91 children aged between 6 months and 4 years. Study duration was from 7 to 16 months; all studies were conducted in emergency departments in the USA (two studies) and Spain. Heliox was administered as a mixture of 70% heliox and 30% oxygen. Risk of bias was low in two studies and high in one study due to an open‐label design. We added no new trials for this update. One study of 15 children with mild croup compared heliox with 30% humidified oxygen administered for 20 minutes. There may be no difference in croup score changes between groups at 20 minutes (mean difference (MD) ‐0.83, 95% confidence interval (CI) ‐2.36 to 0.70). The mean croup score at 20 minutes postintervention may not differ between groups (MD ‐0.57, 95% CI ‐1.46 to 0.32). There may be no difference between groups in mean respiratory rate (MD 6.40, 95% CI ‐1.38 to 14.18) and mean heart rate (MD 14.50, 95% CI ‐8.49 to 37.49) at 20 minutes. The evidence for all outcomes in this comparison was of low quality, downgraded for serious imprecision. All children were discharged, but information on hospitalisation, intubation, or re‐presenting to emergency departments was not reported. In another study, 47 children with moderate croup received one dose of oral dexamethasone (0.3 mg/kg) with either heliox for 60 minutes or no treatment. Heliox may slightly improve croup scores at 60 minutes postintervention (MD ‐1.10, 95% CI ‐1.96 to ‐0.24), but there may be no difference between groups at 120 minutes (MD ‐0.70, 95% CI ‐4.86 to 3.46). Children treated with heliox may have lower mean Taussig croup scores at 60 minutes (MD ‐1.11, 95% CI ‐2.05 to ‐0.17) but not at 120 minutes (MD ‐0.71, 95% CI ‐1.72 to 0.30). Children treated with heliox may have lower mean respiratory rates at 60 minutes (MD ‐4.94, 95% CI ‐9.66 to ‐0.22), but there may be no difference at 120 minutes (MD ‐3.17, 95% CI ‐7.83 to 1.49). There may be no difference in hospitalisation rates between groups (OR 0.46, 95% CI 0.04 to 5.41). We assessed the evidence for all outcomes in this comparison as of low quality, downgraded due to imprecision and high risk of bias related to open‐label design. Information on heart rate and intubation was not reported. In the third study, 29 children with moderate to severe croup received intramuscular dexamethasone (0.6 mg/kg) and either heliox with one to two doses of nebulised saline, or 100% oxygen with one to two doses of adrenaline for three hours. Heliox may slightly improve croup scores at 90 minutes postintervention, but may have little or no difference overall using repeated measures analysis. We assessed the evidence for all outcomes in this comparison as of low quality, downgraded due to high risk of bias related to inadequate reporting. Information on hospitalisation or re‐presenting to the emergency department was not reported. The included studies did not report on adverse events, intensive care admissions, or parental anxiety. We could not pool the available data because each comparison included data from only one study. AUTHORS' CONCLUSIONS: Due to very limited evidence, uncertainty remains about the effectiveness and safety of heliox. Heliox may not be more effective than 30% humidified oxygen for children with mild croup, but may be beneficial in the short term for children with moderate to severe croup treated with dexamethasone. The effect may be similar to 100% oxygen given with one or two doses of adrenaline. Adverse events were not reported, and it is unclear if these were monitored in the included studies. Adequately powered RCTs comparing heliox with standard treatments are needed to further assess the role of heliox in the treatment of children with moderate to severe croup.",,"['Moraa, Irene', 'Sturman, Nancy', 'McGuire, Treasure M', 'van Driel, Mieke L']",,,,
,PMC,The Coronavirus Transmissible Gastroenteritis Virus Evades the Type I Interferon Response through IRE1α-Mediated Manipulation of the MicroRNA miR-30a-5p/SOCS1/3 Axis,http://dx.doi.org/10.1128/JVI.00728-18,PMC6206482,,,"In host innate immunity, type I interferons (IFN-I) are major antiviral molecules, and coronaviruses have evolved diverse strategies to counter the IFN-I response during infection. Transmissible gastroenteritis virus (TGEV), a member of the Alphacoronavirus family, induces endoplasmic reticulum (ER) stress and significant IFN-I production after infection. However, how TGEV evades the IFN-I antiviral response despite the marked induction of endogenous IFN-I has remained unclear. Inositol-requiring enzyme 1 α (IRE1α), a highly conserved ER stress sensor with both kinase and RNase activities, is involved in the IFN response. In this study, IRE1α facilitated TGEV replication via downmodulating the host microRNA (miR) miR-30a-5p abundance. miR-30a-5p normally enhances IFN-I antiviral activity by directly targeting the negative regulators of Janus family kinase (JAK)-signal transducer and activator of transcription (STAT), the suppressor of cytokine signaling protein 1 (SOCS1), and SOCS3. Furthermore, TGEV infection increased SOCS1 and SOCS3 expression, which dampened the IFN-I antiviral response and facilitated TGEV replication. Importantly, compared with mock infection, TGEV infection in vivo resulted in decreased miR-30a-5p levels and significantly elevated SOCS1 and SOCS3 expression in the piglet ileum. Taken together, our data reveal a new strategy used by TGEV to escape the IFN-I response by engaging the IRE1α–miR-30a-5p/SOCS1/3 axis, thus improving our understanding of how TGEV escapes host innate immune defenses. IMPORTANCE Type I interferons (IFN-I) play essential roles in restricting viral infections. Coronavirus infection induces ER stress and the interferon response, which reflects different adaptive cellular processes. An understanding of how coronavirus-elicited ER stress is actively involved in viral replication and manipulates the host IFN-I response has remained elusive. Here, TGEV inhibited host miR-30a-5p via the ER stress sensor IRE1α, which led to the increased expression of negative regulators of JAK-STAT signaling cascades, namely, SOCS1 and SOCS3. Increased SOCS1 or SOCS3 expression impaired the IFN-I antiviral response, promoting TGEV replication. These findings enhance our understanding of the strategies used by coronaviruses to antagonize IFN-I innate immunity via IRE1α-mediated manipulation of the miR-30a-5p/SOCS axis, highlighting the crucial role of IRE1α in innate antiviral resistance and the potential of IRE1α as a novel target against coronavirus infection.",,"['Ma, Yanlong', 'Wang, Changlin', 'Xue, Mei', 'Fu, Fang', 'Zhang, Xin', 'Li, Liang', 'Yin, Lingdan', 'Xu, Wanhai', 'Feng, Li', 'Liu, Pinghuang']",,,,
,PMC,Influenza A Virus M2 Protein Apical Targeting Is Required for Efficient Virus Replication,http://dx.doi.org/10.1128/JVI.01425-18,PMC6206479,,,"The influenza A virus (IAV) M2 protein is a multifunctional protein with critical roles in virion entry, assembly, and budding. M2 is targeted to the apical plasma membrane of polarized epithelial cells, and the interaction of the viral proteins M2, M1, HA, and NA near glycolipid rafts in the apical plasma membrane is hypothesized to coordinate the assembly of infectious virus particles. To determine the role of M2 protein apical targeting in IAV replication, a panel of M2 proteins with basolateral plasma membrane (M2-Baso) or endoplasmic reticulum (M2-ER) targeting sequences was generated. MDCK II cells stably expressing M2-Baso, but not M2-ER, complemented the replication of M2-stop viruses. However, in primary human nasal epithelial cell (hNEC) cultures, viruses encoding M2-Baso and M2-ER replicated to negligible titers compared to those of wild-type virus. M2-Baso replication was negatively correlated with cell polarization. These results demonstrate that M2 apical targeting is essential for IAV replication: targeting M2 to the ER results in a strong, cell type-independent inhibition of virus replication, and targeting M2 to the basolateral membrane has greater effects in hNECs than in MDCK cells. IMPORTANCE Influenza A virus assembly and particle release occur at the apical membrane of polarized epithelial cells. The integral membrane proteins encoded by the virus, HA, NA, and M2, are all targeted to the apical membrane and believed to recruit the other structural proteins to sites of virus assembly. By targeting M2 to the basolateral or endoplasmic reticulum membranes, influenza A virus replication was significantly reduced. Basolateral targeting of M2 reduced the infectious virus titers with minimal effects on virus particle release, while targeting to the endoplasmic reticulum resulted in reduced infectious and total virus particle release. Therefore, altering the expression and the intracellular targeting of M2 has major effects on virus replication.",,"['Wohlgemuth, Nicholas', 'Lane, Andrew P.', 'Pekosz, Andrew']",,,,
,PMC,Structural and Biochemical Characterization of Endoribonuclease Nsp15 Encoded by Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.00893-18,PMC6206473,,,"Nonstructural protein 15 (Nsp15) encoded by coronavirus (CoV) is a nidoviral uridylate-specific endoribonuclease (NendoU) that plays an essential role in the life cycle of the virus. Structural information on this crucial protein from the Middle East respiratory syndrome CoV (MERS-CoV), which is lethally pathogenic and has caused severe respiratory diseases worldwide, is lacking. Here, we determined the crystal structure of MERS-CoV Nsp15 at a 2.7-Å resolution and performed the relevant biochemical assays to study how NendoU activity is regulated. Although the overall structure is conserved, MERS-CoV Nsp15 shows unique and novel features compared to its homologs. Serine substitution of residue F285, which harbors an aromatic side chain that disturbs RNA binding compared with that of other homologs, increases catalytic activity. Mutations of residues residing on the oligomerization interfaces that distort hexamerization, namely, N38A, Y58A, and N157A, decrease thermostability, decrease affinity of binding with RNA, and reduce the NendoU activity of Nsp15. In contrast, mutant D39A exhibits increased activity and a higher substrate binding capacity. Importantly, Nsp8 was found to interact with both monomeric and hexameric Nsp15. The Nsp7/Nsp8 complex displays a higher binding affinity for Nsp15. Furthermore, Nsp8 and the Nsp7/Nsp8 complex also enhance the NendoU activity of hexameric Nsp15 in vitro. Taking the findings together, this work first provides evidence on how the activity of Nsp15 may be functionally mediated by catalytic residues, oligomeric assembly, RNA binding efficiency, or the possible association with other nonstructural proteins. IMPORTANCE The lethally pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) and the severe acute respiratory syndrome coronavirus (SARS-CoV) pose serious threats to humans. Endoribonuclease Nsp15 encoded by coronavirus plays an important role in viral infection and pathogenesis. This study determines the structure of MERS-CoV Nsp15 and demonstrates how the catalytic activity of this protein is potentially mediated, thereby providing structural and functional evidence for developing antiviral drugs. We also hypothesize that the primase-like protein Nsp8 and the Nsp7/Nsp8 complex may interact with Nsp15 and affect enzymatic activity. This contributes to the understanding of the association of Nsp15 with the viral replication and transcription machinery.",,"['Zhang, Lianqi', 'Li, Lei', 'Yan, Liming', 'Ming, Zhenhua', 'Jia, Zhihui', 'Lou, Zhiyong', 'Rao, Zihe']",,,,
,PMC,Exchange Proteins Directly Activated by cAMP and Their Roles in Respiratory Syncytial Virus Infection,http://dx.doi.org/10.1128/JVI.01200-18,PMC6206471,,,"Respiratory syncytial virus (RSV) is the leading cause of respiratory infection in young children and high-risk adults. However, a specific treatment for this viral infection is not currently available. In this study, we discovered that an exchange protein directly activated by cyclic AMP (EPAC) can serve as a potential therapeutic target for RSV. In both lower and upper epithelial cells, treatment with EPAC inhibitor (ESI-09), but not protein kinase A inhibitor (H89), significantly inhibits RSV replication and proinflammatory cytokine/chemokine induction. In addition, RSV-activated transcriptional factors belonging to the NF-κB and IRF families are also suppressed by ESI-09. Through isoform-specific gene knockdown, we found that EPAC2, but not EPAC1, plays a dominant role in controlling RSV replication and virus-induced host responses. Experiments using both EPAC2 knockout and EPAC2-specific inhibitor support such roles of EPAC2. Therefore, EPAC2 is a promising therapeutic target to regulate RSV replication and associated inflammation. IMPORTANCE RSV is a serious public health problem, as it is associated with bronchiolitis, pneumonia, and asthma exacerbations. Currently no effective treatment or vaccine is available, and many molecular mechanisms regarding RSV-induced lung disease are still significantly unknown. This project aims to elucidate an important and novel function of a protein, called EPAC2, in RSV replication and innate inflammatory responses. Our results should provide an important insight into the development of new pharmacologic strategies against RSV infection, thereby reducing RSV-associated morbidity and mortality.",,"['Choi, Eun-Jin', 'Ren, Yuping', 'Chen, Yu', 'Liu, Shengxuan', 'Wu, Wenzhe', 'Ren, Junping', 'Wang, Pingyuan', 'Garofalo, Roberto P.', 'Zhou, Jia', 'Bao, Xiaoyong']",,,,
,PMC,Significant Spike-Specific IgG and Neutralizing Antibodies in Mice Induced by a Novel Chimeric Virus-Like Particle Vaccine Candidate for Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1007/s12250-018-0064-8,PMC6235757,,,,,"['Lan, Jiaming', 'Deng, Yao', 'Song, Jingdong', 'Huang, Baoying', 'Wang, Wenling', 'Tan, Wenjie']",,,,
,PMC,Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age,http://dx.doi.org/10.1128/IAI.00282-18,PMC6204695,,,"Tissues and organs provide the structural and biochemical landscapes upon which microbial pathogens and commensals function to regulate health and disease. While flat two-dimensional (2-D) monolayers composed of a single cell type have provided important insight into understanding host-pathogen interactions and infectious disease mechanisms, these reductionist models lack many essential features present in the native host microenvironment that are known to regulate infection, including three-dimensional (3-D) architecture, multicellular complexity, commensal microbiota, gas exchange and nutrient gradients, and physiologically relevant biomechanical forces (e.g., fluid shear, stretch, compression). A major challenge in tissue engineering for infectious disease research is recreating this dynamic 3-D microenvironment (biological, chemical, and physical/mechanical) to more accurately model the initiation and progression of host-pathogen interactions in the laboratory. Here we review selected 3-D models of human intestinal mucosa, which represent a major portal of entry for infectious pathogens and an important niche for commensal microbiota. We highlight seminal studies that have used these models to interrogate host-pathogen interactions and infectious disease mechanisms, and we present this literature in the appropriate historical context. Models discussed include 3-D organotypic cultures engineered in the rotating wall vessel (RWV) bioreactor, extracellular matrix (ECM)-embedded/organoid models, and organ-on-a-chip (OAC) models. Collectively, these technologies provide a more physiologically relevant and predictive framework for investigating infectious disease mechanisms and antimicrobial therapies at the intersection of the host, microbe, and their local microenvironments.",,"['Barrila, Jennifer', 'Crabbé, Aurélie', 'Yang, Jiseon', 'Franco, Karla', 'Nydam, Seth D.', 'Forsyth, Rebecca J.', 'Davis, Richard R.', 'Gangaraju, Sandhya', 'Ott, C. Mark', 'Coyne, Carolyn B.', 'Bissell, Mina J.', 'Nickerson, Cheryl A.']",,,,
,PMC,PNAS Plus Significance Statements,http://dx.doi.org/10.1073/pnas.ss11543,PMC6205431,,,,,,,,,
,PMC,Identification of Nonstructural Protein 8 as the N-Terminus of the RNA-Dependent RNA Polymerase of Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1007/s12250-018-0054-x,PMC6235764,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) is a member within the family Arteriviridae of the order Nidovirales. Replication of this positive-stranded RNA virus within the host cell involves expression of viral replicase proteins encoded by two ORFs, namely ORF1a and ORF1b. In particular, translation of ORF1b depends on a -1-ribosomal frameshift strategy. Thus, nonstructural protein 9 (nsp9), the first protein within ORF1b that specifies the function of the viral RNA-dependent RNA polymerase, is expressed as the C-terminal extension of nsp8, a small nsp that is encoded by ORF1a. However, it has remained unclear whether the mature form of nsp9 in virus-infected cells still retains nsp8, addressing which is clearly critical to understand the biological function of nsp9. By taking advantage of specific antibodies to both nsp8 and nsp9, we report the following findings. (1) In infected cells, PRRSV nsp9 was identified as a major product with a size between 72 and 95 kDa (72–95 KDa form), which exhibited the similar mobility on the gel to the in vitro expressed nsp8–9(ORF1b), but not the ORF1b-coded portion (nsp9(ORF1b)). (2) The antibodies to nsp8, but not to nsp7 or nsp10, could detect a major product that had the similar mobility to the 72–95 KDa form of nsp9. Moreover, nsp9 could be co-immunoprecipitated by antibodies to nsp8, and vice versa. (3) Neither nsp4 nor nsp2 PLP2 was able to cleave nsp8–nsp9 in vitro. Together, our studies provide experimental evidence to suggest that nsp8 is an N-terminal extension of nsp9. Our findings here paves way for further charactering the biological function of PRRSV nsp9. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-018-0054-x) contains supplementary material, which is available to authorized users.",,"['Liu, Yuanyuan', 'Hu, Yunhao', 'Chai, Yue', 'Liu, Liping', 'Song, Jiangwei', 'Zhou, Shaochuan', 'Su, Jia', 'Zhou, Lei', 'Ge, Xinna', 'Guo, Xin', 'Han, Jun', 'Yang, Hanchun']",,,,
,PMC,Professor Hu Zhihong: The New President of the Society for Invertebrate Pathology,http://dx.doi.org/10.1007/s12250-018-0060-z,PMC6235762,,,,,"['Arif, Basil', 'Si, Jiali', 'Shi, Zheng-Li']",,,,
,PMC,Prophylactic and therapeutic approaches for human metapneumovirus,http://dx.doi.org/10.1007/s13337-018-0498-5,PMC6261883,,,Human metapneumovirus (HMPV) is an important pneumovirus which causes acute respiratory disease in human beings. The viral infection leads to mild to severe respiratory symptoms depending on the age and immune status of the infected individual. Several groups across the world are working on the development of immunogens and therapy to manage HMPV infection with promising results under laboratory conditions but till date any virus specific vaccine or therapy has not been approved for clinical use. This minireview gives an overview of the prophylactic and therapeutic approaches to manage HMPV infections.,,"['Kumar, Prashant', 'Srivastava, Mansi']",,,,
,PMC,"Protease inhibitors broadly effective against feline, ferret and mink coronaviruses",http://dx.doi.org/10.1016/j.antiviral.2018.10.015,PMC6240502,,,"Ferret and mink coronaviruses typically cause catarrhal diarrhea in ferrets and minks, respectively. In recent years, however, systemic fatal coronavirus infection has emerged in ferrets, which resembles feline infectious peritonitis (FIP) in cats. FIP is a highly fatal systemic disease caused by a virulent feline coronavirus infection in cats. Despite the importance of coronavirus infections in these animals, there are no effective commercial vaccines or antiviral drugs available for these infections. We have previously reported the efficacy of a protease inhibitor in cats with FIP, demonstrating that a virally encoded 3C-like protease (3CLpro) is a valid target for antiviral drug development for coronavirus infections. In this study, we extended our previous work on coronavirus inhibitors and investigated the structure-activity relationships of a focused library of protease inhibitors for ferret and mink 3CLpro. Using the fluorescence resonance energy transfer assay, we identified potent inhibitors broadly effective against feline, ferret and mink coronavirus 3CLpro. Multiple amino acid sequence analysis and modelling of 3CLpro of ferret and mink coronaviruses were conducted to probe the structural basis for these findings. The results of this study provide support for further research to develop broad-spectrum antiviral agents for multiple coronavirus infections. To the best of our knowledge, this is the first report on small molecule inhibitors of ferret and mink coronaviruses.",,"['Perera, Krishani Dinali', 'Kankanamalage, Anushka C. Galasiti', 'Rathnayake, Athri D.', 'Honeyfield, Amanda', 'Groutas, William', 'Chang, Kyeong-Ok', 'Kim, Yunjeong']",,,,
,PMC,Automatically fixing errors in glycoprotein structures with Rosetta,http://dx.doi.org/10.1016/j.str.2018.09.006,PMC6616339,,,"Recent advances in single-particle cryo-electron microscopy (cryoEM) have resulted in determination of an increasing number of protein structures with resolved glycans. However, existing protocols for the refinement of glycoproteins at low resolution have failed to keep up with these advances. As a result, numerous deposited structures contain glycan stereochemical errors. Here, we describe a Rosetta-based approach for both cryoEM and X-ray crystallography refinement of glycoproteins which is capable of correcting conformational and configurational errors in carbohydrates. Building upon a previous Rosetta framework, we introduced additional features and score terms enabling automatic detection, setup and refinement of glycan-containing structures. We benchmarked this approach using twelve crystal structures and showed that glycan geometries can be automatically improved while maintaining good fit to the crystallographic data. Finally, we used this method to refine carbohydrates of the human coronavirus NL63 spike glycoprotein and of an HIV envelope glycoprotein, demonstrating its usefulness for cryoEM refinement.",,"['Frenz, Brandon', 'Rämisch, Sebastian', 'Borst, Andrew J.', 'Walls, Alexandra C.', 'Adolf-Bryfogle, Jared', 'Schief, William R.', 'Veesler, David', 'DiMaio, Frank']",,,,
,PMC,Analyzing Vaccine Trials in Epidemics With Mild and Asymptomatic Infection,http://dx.doi.org/10.1093/aje/kwy239,PMC6357804,,,"Vaccine efficacy against susceptibility to infection (VE(S)), regardless of symptoms, is an important endpoint of vaccine trials for pathogens with a high proportion of asymptomatic infection, because such infections may contribute to onward transmission and long-term sequelae, such as congenital Zika syndrome. However, estimating VE(S) is resource-intensive. We aimed to identify approaches for accurately estimating VE(S) when limited information is available and resources are constrained. We modeled an individually randomized vaccine trial by generating a network of individuals and simulating an epidemic. The disease natural history followed a “susceptible-exposed-infectious/symptomatic (or infectious/asymptomatic)-recovered” model. We then used 7 approaches to estimate VE(S), and we also estimated vaccine efficacy against progression to symptoms (VE(P)). A corrected relative risk and an interval-censored Cox model accurately estimate VE(S) and only require serological testing of participants once, while a Cox model using only symptomatic infections returns biased estimates. Only acquiring serological endpoints in a 10% sample and imputing the remaining infection statuses yields unbiased VE(S) estimates across values of the basic reproduction number (R(0)) and accurate estimates of VE(P) for higher R(0) values. Identifying resource-preserving methods for accurately estimating VE(S) and VE(P) is important in designing trials for diseases with a high proportion of asymptomatic infection.",,"['Kahn, Rebecca', 'Hitchings, Matt', 'Wang, Rui', 'Bellan, Steven E', 'Lipsitch, Marc']",,,,
,PMC,Antibody-mediated protection against Ebola virus,http://dx.doi.org/10.1038/s41590-018-0233-9,PMC6814399,,,"Recent Ebola virus disease epidemics have highlighted the need for effective vaccines and therapeutics to prevent future outbreaks. Antibodies are clearly critical for control of this deadly disease; however, the specific mechanisms of action of protective antibodies have yet to be defined. In this Perspective we discuss the antibody features that correlate with in vivo protection during infection with Ebola virus, based on the results of a systematic and comprehensive study of antibodies directed against this virus. Although neutralization activity mediated by the Fab domains of the antibody is strongly correlated with protection, recruitment of immune effector functions by the Fc domain has also emerged as a complementary, and sometimes alternative, route to protection. For a subset of antibodies, Fc-mediated clearance and killing of infected cells seems to be the main driver of protection after exposure and mirrors observations in vaccination studies. Continued analysis of antibodies that achieve protection partially or wholly through Fc-mediated functions, the precise functions required, the intersection with specificity and the importance of these functions in different animal models is needed to identify and begin to capitalize on Fc-mediated protection in vaccines and therapeutics alike.",,"['Saphire, Erica Ollmann', 'Schendel, Sharon L.', 'Gunn, Bronwyn M.', 'Milligan, Jacob C.', 'Alter, Galit']",,,,
,PMC,Location is everything: protein translocations as a viral infection strategy,http://dx.doi.org/10.1016/j.cbpa.2018.09.021,PMC6382524,,,"Protein movement between different subcellular compartments is an essential aspect of biological processes, including transcriptional and metabolic regulation, and immune and stress responses. As obligate intracellular parasites, viruses are master manipulators of cellular composition and organization. Accumulating evidences have highlighted the importance of infection-induced protein translocations between organelles. Both directional and temporal, these translocation events facilitate localization-dependent protein interactions and changes in protein functions that contribute to either host defense or virus replication. The discovery and characterization of protein movement is technically challenging, given the necessity for sensitive detection and subcellular resolution. Here, we discuss infection-induced translocations of host and viral proteins, and the value of integrating quantitative proteomics with advanced microscopy for understanding the biology of human virus infections.",,"['Cook, Katelyn C.', 'Cristea, Ileana M.']",,,,
,PMC,Not your usual tRNA synthetase: hWARS serves as an enterovirus entry factor,http://dx.doi.org/10.1172/JCI124582,PMC6205376,,,"Enteroviruses, including subtype EV-A71, infect the brain, liver, heart, and other organs, causing a myriad of human diseases. This spectrum of disease is thought to be due, in part, to differential binding to host cells, and additional knowledge of enterovirus cell entry is essential for therapeutic development. In this issue of the JCI, Yeung et al. provide evidence of a novel EV-A71 entry factor, a host-produced tryptophan tRNA synthetase (hWARS), that facilitates entry of multiple subtypes of enteroviruses. hWARS is a cytoplasmic enzyme that is essential for translation but also upregulated and secreted during inflammatory processes. The results of this study support the notion of secreted hWARS as an unconventional virus entry factor that raises interesting questions about mechanisms by which inflammation and a tRNA synthetase facilitate viral pathogenesis.",,"['Perlman, Stanley', 'Gallagher, Tom']",,,,
,PMC,Human tryptophanyl-tRNA synthetase is an IFN-γ–inducible entry factor for Enterovirus,http://dx.doi.org/10.1172/JCI99411,PMC6205371,,,"Enterovirus A71 (EV-A71) receptors that have been identified to date cannot fully explain the pathogenesis of EV-A71, which is an important global cause of hand, foot, and mouth disease and life-threatening encephalitis. We identified an IFN-γ–inducible EV-A71 cellular entry factor, human tryptophanyl-tRNA synthetase (hWARS), using genome-wide RNAi library screening. The importance of hWARS in mediating virus entry and infectivity was confirmed by virus attachment, in vitro pulldown, antibody/antigen blocking, and CRISPR/Cas9-mediated deletion. Hyperexpression and plasma membrane translocation of hWARS were observed in IFN-γ–treated semipermissive (human neuronal NT2) and cDNA-transfected nonpermissive (mouse fibroblast L929) cells, resulting in their sensitization to EV-A71 infection. Our hWARS-transduced mouse infection model showed pathological changes similar to those seen in patients with severe EV-A71 infection. Expression of hWARS is also required for productive infection by other human enteroviruses, including the clinically important coxsackievirus A16 (CV-A16) and EV-D68. This is the first report to our knowledge on the discovery of an entry factor, hWARS, that can be induced by IFN-γ for EV-A71 infection. Given that we detected high levels of IFN-γ in patients with severe EV-A71 infection, our findings extend the knowledge of the pathogenicity of EV-A71 in relation to entry factor expression upon IFN-γ stimulation and the therapeutic options for treating severe EV-A71–associated complications.",,"['Yeung, Man Lung', 'Jia, Lilong', 'Yip, Cyril C. Y.', 'Chan, Jasper F. W.', 'Teng, Jade L. L.', 'Chan, Kwok-Hung', 'Cai, Jian-Piao', 'Zhang, Chaoyu', 'Zhang, Anna J.', 'Wong, Wan-Man', 'Kok, Kin-Hang', 'Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Lo, Janice Y. C.', 'Jin, Dong-Yan', 'Shih, Shin-Ru', 'Yuen, Kwok-Yung']",,,,
,PMC,So Many Roads: the Multifaceted Regulation of Autophagy Induction,http://dx.doi.org/10.1128/MCB.00303-18,PMC6189458,,,"Autophagy is an evolutionary conserved, degradative process from single-cell eukaryotes, such as Saccharomyces cerevisiae, to higher mammals, such as humans. The regulation of autophagy has been elucidated through the combined study of yeast, Caenorhabditis elegans, mice, Drosophila melanogaster, and humans. MTOR, the major negative regulator of autophagy, and activating nutrient kinases, such as 5′-AMP-activated protein kinase (AMPK), interact with the autophagy regulatory complex: ULK1/2, RB1CC1, ATG13, and ATG101. The ULK1/2 complex induces autophagy by phosphorylating downstream autophagy complexes, such as the BECN1 PIK3 signaling complex that leads to the creation of LC3(+) autophagosomes. We highlight in this review various reports of autophagy induction that are independent of these regulators. We discuss reports of MTOR-independent, AMPK-independent, ULK1/2-independent, and BECN1-PIK3C3-independent autophagy. We illustrate that autophagy induction and the components required vary by the nature of the induction signal and type of cell and do not always require canonical members of the autophagy signaling pathway. We illustrate that rather than thinking of autophagy as a linear pathway, it is better to think of autophagy induction as an interconnecting web of key regulators, many of which can induce autophagy through different requirements depending on the type and length of induction signals.",,"['Corona Velazquez, Angel F.', 'Jackson, William T.']",,,,
,PMC,ADP-ribosyl–binding and hydrolase activities of the alphavirus nsP3 macrodomain are critical for initiation of virus replication,http://dx.doi.org/10.1073/pnas.1812130115,PMC6217424,,,"Alphaviruses are plus-strand RNA viruses that cause encephalitis, rash, and arthritis. The nonstructural protein (nsP) precursor polyprotein is translated from genomic RNA and processed into four nsPs. nsP3 has a highly conserved macrodomain (MD) that binds ADP-ribose (ADPr), which can be conjugated to protein as a posttranslational modification involving transfer of ADPr from NAD(+) by poly ADPr polymerases (PARPs). The nsP3(MD) also removes ADPr from mono ADP-ribosylated (MARylated) substrates. To determine which aspects of alphavirus replication require nsP3(MD) ADPr-binding and/or hydrolysis function, we studied NSC34 neuronal cells infected with chikungunya virus (CHIKV). Infection induced ADP-ribosylation of cellular proteins without increasing PARP expression, and inhibition of MARylation decreased virus replication. CHIKV with a G32S mutation that reduced ADPr-binding and hydrolase activities was less efficient than WT CHIKV in establishing infection and in producing nsPs, dsRNA, viral RNA, and infectious virus. CHIKV with a Y114A mutation that increased ADPr binding but reduced hydrolase activity, established infection like WT CHIKV, rapidly induced nsP translation, and shut off host protein synthesis with reduced amplification of dsRNA. To assess replicase function independent of virus infection, a transreplicase system was used. Mutant nsP3(MD)s D10A, G32E, and G112E with no binding or hydrolase activity had no replicase activity, G32S had little, and Y114A was intermediate to WT. Therefore, ADP ribosylation of proteins and nsP3(MD) ADPr binding are necessary for initiation of alphavirus replication, while hydrolase activity facilitates amplification of replication complexes. These observations are consistent with observed nsP3(MD) conservation and limited tolerance for mutation.",,"['Abraham, Rachy', 'Hauer, Debra', 'McPherson, Robert Lyle', 'Utt, Age', 'Kirby, Ilsa T.', 'Cohen, Michael S.', 'Merits, Andres', 'Leung, Anthony K. L.', 'Griffin, Diane E.']",,,,
,PMC,Increased Levels of Circulating Glial Fibrillary Acidic Protein and Collapsin Response Mediator Protein-2 Autoantibodies in the Acute Stage of Spinal Cord Injury Predict the Subsequent Development of Neuropathic Pain,http://dx.doi.org/10.1089/neu.2018.5675,PMC6909673,,,"Neuropathic pain develops in 40–70% of spinal cord injury (SCI) patients and markedly compromises quality of life. We examined plasma from SCI patients for autoantibodies to glial fibrillary acidic protein (GFAP) and collapsin response mediator protein-2 (CRMP2) and evaluated their relationship to the development of neuropathic pain. In study 1, plasma samples and clinical data from 80 chronic SCI patients (1–41 years post-SCI) were collected and screened for GFAP autoantibodies (GFAPab). Results from study 1 indicated that GFAPab were present in 34 of 80 (42.5%) patients, but circulating levels did not correlate with the occurrence of neuropathic pain. In study 2, longitudinal plasma samples and clinical data were collected from 38 acute SCI patients. The level of GFAPab measured at 16 ± 7 days post-SCI was found to be significantly higher in patients that subsequently developed neuropathic pain (within 6 months post-SCI) than patients who did not (T = 219; p = 0.02). In study 3, we identified CRMP2 as an autoantibody target (CRMP2ab) in 23% of acute SCI patients. The presence of GFAPab and/or CRMP2ab increased the odds of subsequently developing neuropathic pain within 6 months of injury by 9.5 times (p = 0.006). Our results suggest that if a causal link can be established between these autoantibodies and the development of neuropathic pain, strategies aimed at reducing the circulating levels of these autoantibodies may have therapeutic value.",,"['Hergenroeder, Georgene W.', 'Redell, John B.', 'Choi, H. Alex', 'Schmitt, Lisa', 'Donovan, William', 'Francisco, Gerard E.', 'Schmitt, Karl', 'Moore, Anthony N.', 'Dash, Pramod K.']",,,,
,PMC,Surfactin Inhibits Membrane Fusion during Invasion of Epithelial Cells by Enveloped Viruses,http://dx.doi.org/10.1128/JVI.00809-18,PMC6189506,,,"Because membrane fusion is a crucial step in the process by which enveloped viruses invade host cells, membrane fusion inhibitors can be effective drugs against enveloped viruses. We found that surfactin from Bacillus subtilis can suppress the proliferation of porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) in epithelial cells at a relatively low concentration range (15 to 50 μg/ml), without cytotoxicity or viral membrane disruption. Membrane fusion inhibition experiments demonstrate that surfactin treatment significantly reduces the rate at which the virus fuses to the cell membrane. Thermodynamic experiments show that the incorporation of small amounts of surfactin hinders the formation of negative curvature by lamellar-phase lipids, suggesting that surfactin acts a membrane fusion inhibitor. A fluorescent lipopeptide similar to surfactin was synthesized, and its ability to insert into the viral membrane was confirmed by spectroscopy. In vivo experiments have shown that oral administration of surfactin to piglets protects against PEDV infection. In conclusion, our study indicates that surfactin is a membrane fusion inhibitor with activity against enveloped viruses. As the first reported naturally occurring wedge lipid membrane fusion inhibitor, surfactin is likely to be a prototype for the development of a broad range of novel antiviral drugs. IMPORTANCE Membrane fusion inhibitors are a rapidly emerging class of antiviral drugs that inhibit the infection process of enveloped viruses. They can be classified, on the basis of the viral components targeted, as fusion protein targeting or membrane lipid targeting. Lipid-targeting membrane fusion inhibitors have a broader antiviral spectrum and are less likely to select for drug-resistant mutations. Here we show that surfactin is a membrane fusion inhibitor and has a strong antiviral effect. The insertion of surfactin into the viral envelope lipids reduces the probability of viral fusion. We also demonstrate that oral administration of surfactin protects piglets from PEDV infection. Surfactin is the first naturally occurring wedge lipid membrane fusion inhibitor that has been identified and may be effective against many viruses beyond the scope of this study. Understanding its mechanism of action provides a foundation for the development of novel antiviral agents.",,"['Yuan, Lvfeng', 'Zhang, Shuai', 'Wang, Yongheng', 'Li, Yuchen', 'Wang, Xiaoqing', 'Yang, Qian']",,,,
,PMC,The Endonucleolytic RNA Cleavage Function of nsp1 of Middle East Respiratory Syndrome Coronavirus Promotes the Production of Infectious Virus Particles in Specific Human Cell Lines,http://dx.doi.org/10.1128/JVI.01157-18,PMC6189501,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) nsp1 suppresses host gene expression in expressed cells by inhibiting translation and inducing endonucleolytic cleavage of host mRNAs, the latter of which leads to mRNA decay. We examined the biological functions of nsp1 in infected cells and its role in virus replication by using wild-type MERS-CoV and two mutant viruses with specific mutations in the nsp1; one mutant lacked both biological functions, while the other lacked the RNA cleavage function but retained the translation inhibition function. In Vero cells, all three viruses replicated efficiently with similar replication kinetics, while wild-type virus induced stronger host translational suppression and host mRNA degradation than the mutants, demonstrating that nsp1 suppressed host gene expression in infected cells. The mutant viruses replicated less efficiently than wild-type virus in Huh-7 cells, HeLa-derived cells, and 293-derived cells, the latter two of which stably expressed a viral receptor protein. In 293-derived cells, the three viruses accumulated similar levels of nsp1 and major viral structural proteins and did not induce IFN-β and IFN-λ mRNAs; however, both mutants were unable to generate intracellular virus particles as efficiently as wild-type virus, leading to inefficient production of infectious viruses. These data strongly suggest that the endonucleolytic RNA cleavage function of the nsp1 promoted MERS-CoV assembly and/or budding in a 293-derived cell line. MERS-CoV nsp1 represents the first CoV gene 1 protein that plays an important role in virus assembly/budding and is the first identified viral protein whose RNA cleavage-inducing function promotes virus assembly/budding. IMPORTANCE MERS-CoV represents a high public health threat. Because CoV nsp1 is a major viral virulence factor, uncovering the biological functions of MERS-CoV nsp1 could contribute to our understanding of MERS-CoV pathogenicity and spur development of medical countermeasures. Expressed MERS-CoV nsp1 suppresses host gene expression, but its biological functions for virus replication and effects on host gene expression in infected cells are largely unexplored. We found that nsp1 suppressed host gene expression in infected cells. Our data further demonstrated that nsp1, which was not detected in virus particles, promoted virus assembly or budding in a 293-derived cell line, leading to efficient virus replication. These data suggest that nsp1 plays an important role in MERS-CoV replication and possibly affects virus-induced diseases by promoting virus particle production in infected hosts. Our data, which uncovered an unexpected novel biological function of nsp1 in virus replication, contribute to further understanding of the MERS-CoV replication strategies.",,"['Nakagawa, Keisuke', 'Narayanan, Krishna', 'Wada, Masami', 'Popov, Vsevolod L.', 'Cajimat, Maria', 'Baric, Ralph S.', 'Makino, Shinji']",,,,
,PMC,Direct Diagnostic Tests for Lyme Disease,http://dx.doi.org/10.1093/cid/ciy614,PMC6399434,,,"Borrelia burgdorferi was discovered to be the cause of Lyme disease in 1983, leading to seroassays. The 1994 serodiagnostic testing guidelines predated a full understanding of key B. burgdorferi antigens and have a number of shortcomings. These serologic tests cannot distinguish active infection, past infection, or reinfection. Reliable direct-detection methods for active B. burgdorferi infection have been lacking in the past but are needed and appear achievable. New approaches have effectively been applied to other emerging infections and show promise in direct detection of B. burgdorferi infections.",,"['Schutzer, Steven E', 'Body, Barbara A', 'Boyle, Jeff', 'Branson, Bernard M', 'Dattwyler, Raymond J', 'Fikrig, Erol', 'Gerald, Noel J', 'Gomes-Solecki, Maria', 'Kintrup, Martin', 'Ledizet, Michel', 'Levin, Andrew E', 'Lewinski, Michael', 'Liotta, Lance A', 'Marques, Adriana', 'Mead, Paul S', 'Mongodin, Emmanuel F', 'Pillai, Segaran', 'Rao, Prasad', 'Robinson, William H', 'Roth, Kristian M', 'Schriefer, Martin E', 'Slezak, Thomas', 'Snyder, Jessica L', 'Steere, Allen C', 'Witkowski, Jan', 'Wong, Susan J', 'Branda, John A']",,,,
,PMC,Countrywide Survey for MERS-Coronavirus Antibodies in Dromedaries and Humans in Pakistan,http://dx.doi.org/10.1007/s12250-018-0051-0,PMC6235758,,,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a zoonotic pathogen capable of causing severe respiratory disease in humans. Although dromedary camels are considered as a major reservoir host, the MERS-CoV infection dynamics in camels are not fully understood. Through surveillance in Pakistan, nasal (n = 776) and serum (n = 1050) samples were collected from camels between November 2015 and February 2018. Samples were collected from animal markets, free-roaming herds and abattoirs. An in-house ELISA was developed to detect IgG against MERS-CoV. A total of 794 camels were found seropositive for MERS-CoV. Prevalence increased with the age and the highest seroprevalence was recorded in camels aged > 10 years (81.37%) followed by those aged 3.1–10 years (78.65%) and ≤ 3 years (58.19%). Higher prevalence was observed in female (78.13%) as compared to male (70.70%). Of the camel nasal swabs, 22 were found to be positive by RT-qPCR though with high Ct values. Moreover, 2,409 human serum samples were also collected from four provinces of Pakistan during 2016–2017. Among the sampled population, 840 humans were camel herders. Although we found a high rate of MERS-CoV antibody positive dromedaries (75.62%) in Pakistan, no neutralizing antibodies were detected in humans with and without contact to camels.",,"['Zohaib, Ali', 'Saqib, Muhammad', 'Athar, Muhammad Ammar', 'Chen, Jing', 'Sial, Awais-ur-Rahman', 'Khan, Saeed', 'Taj, Zeeshan', 'Sadia, Halima', 'Tahir, Usman', 'Tayyab, Muhammad Haleem', 'Qureshi, Muhammad Asif', 'Mansoor, Muhammad Khalid', 'Naeem, Muhammad Ahsan', 'Hu, Bing-Jie', 'Khan, Bilal Ahmed', 'Ujjan, Ikram Din', 'Li, Bei', 'Zhang, Wei', 'Luo, Yun', 'Zhu, Yan', 'Waruhiu, Cecilia', 'Khan, Iahtasham', 'Yang, Xing-Lou', 'Sajid, Muhammad Sohail', 'Corman, Victor Max', 'Yan, Bing', 'Shi, Zheng-Li']",,,,
,PMC,Recurring and adaptable binding motifs in broadly neutralizing antibodies to influenza virus are encoded on the D3-9 segment of the Ig gene,http://dx.doi.org/10.1016/j.chom.2018.09.010,PMC6327842,,,"Discovery and characterization of broadly neutralizing antibodies (bnAbs) to the influenza hemagglutinin (HA) stem have provided insights for the development of a universal flu vaccine. Identification of signature features common to bnAbs from different individuals will be key to guiding immunogen design. S9-3-37 is a bnAb isolated from a healthy H5N1 vaccinee. Here, structural characterization reveals that the D3-9 gene segment of S9-3-37 contributes most of the interaction surface with the highly conserved stem epitope on HA. Comparison with other influenza bnAb crystal structures indicates that the D3-9 segment provides a general mechanism for targeting HA stem. Interestingly, such bnAbs can approach the HA stem with vastly different angles and orientations. Moreover, D3-9 can be translated in different reading frames in different bnAbs, yet still target the same HA stem pocket. Thus, the D3-9 gene segment in the human immune repertoire can provide a robust defense against influenza virus.",,"['Wu, Nicholas C.', 'Yamayoshi, Seiya', 'Ito, Mutsumi', 'Uraki, Ryuta', 'Kawaoka, Yoshihiro', 'Wilson, Ian A.']",,,,
,PMC,Research Ethics in the European Influenzanet Consortium: Scoping Review,http://dx.doi.org/10.2196/publichealth.9616,PMC6231872,30305258,CC BY,"BACKGROUND: Influenzanet was launched in several European countries to monitor influenza-like illness during flu seasons with the help of volunteering participants and Web-based technologies. As in the case of developing fields, ethical approaches are not well developed in the collection, processing, and analysis of participants’ information. Existing controversies and varying national ethical regulations can, thus, hamper efficient cross-border research collaboration to the detriment of quality disease surveillance. OBJECTIVE: This scoping review characterizes current practices on how ethical, legal, and social issues (ELSIs) pertinent to research ethics are handled by different Influenzanet country groups to analyze similarities and identify the need for further harmonization of ethical approaches. METHODS: A literature search was carried out on PubMed, Web of Science, Global Digital Library on Ethics, and Bioethics Literature Database to identify ELSIs for Influenzanet country platforms. Only English-language papers were included with publication dates from 2003 to 2017. Publications were screened for the application of bioethics principles in the implementation of country platforms. Additional publications gathered from the Influenzanet Consortium website, reference screening, and conference proceeding were screened for ELSIs. RESULTS: We gathered 96 papers from our search methodology. In total, 28 papers that mentioned ELSIs were identified and included in this study. The Research Ethics Committee (REC) approvals were sought for recruiting participants and collecting their data in 8 of 11 country platforms and informed e-consent was sought from participants in 9 of 11 country platforms. Furthermore, personal data protection was ensured throughout the Consortium using data anonymization before processing and analysis and using aggregated data. CONCLUSIONS: Epidemics forecasting activities, such as Influenzanet, are beneficial; however, its benefits could be further increased through the harmonization of data gathering and ethical requirements. This objective is achievable by the Consortium. More transparency should be promoted concerning REC-approved research for Influenzanet-like systems. The validity of informed e-consent could also be increased through the provision of a user friendly and standard information sheet across the Consortium where participants agree to its terms, conditions, and privacy policies before being able to fill in the questionnaire. This will help to build trust in the general public while preventing any decline in participation.",2018 Oct 10,"['Geneviève, Lester Darryl', 'Wangmo, Tenzin', 'Dietrich, Damien', 'Woolley-Meza, Olivia', 'Flahault, Antoine', 'Elger, Bernice Simone']",JMIR Public Health Surveill,,,
,PMC,Pulmonary function and bronchial reactivity 4 years after the first virus-induced wheezing,http://dx.doi.org/10.1111/all.13593,PMC6387855,,,"BACKGROUND: Wheezing illnesses among young children are common, and are a risk factor for asthma. However, determinants of childhood bronchial reactivity, a key feature of asthma, are largely unknown. Aim of this study was to determine how patient characteristics during the first severe virus-induced wheezing episode are associated with pulmonary function at pre-school age. METHODS: Study consisted of 76 children presenting with their first wheezing episode at the ages of 3 to 23 months. At study entry, viral etiology, rhinovirus genome load, atopic and clinical characteristics, and standardized questionnaire were analyzed. At 4-year follow-up visit, impulse oscillometry with exercise challenge was performed. RESULTS: At study entry, the mean age of the children was 12 months (SD 6.0), 57 (75%) were rhinovirus positive and 22 (30%) were sensitized. At follow-up visit four years later, the mean age of the children was 60 months (SD 7.9) and 37 (49%) were using asthma medication regularly (discontinued before testing in 25 [68%] children). Bronchial reactivity (≥35% change in mean crude values of resistance) after exercise challenge or bronchodilation was present in 9 (12%) children. Children with atopic sensitization at the time of the first wheezing episode were more often likely to develop bronchial reactivity (odds ratio 8.8, P = .03) than the children without sensitization. No other significant associations were found. CONCLUSIONS: Atopic sensitization at the time of the first severe wheezing episode is an important early risk factor for increased bronchial reactivity at pre-school age.",,"['Leino, Annamari', 'Lukkarinen, Minna', 'Turunen, Riitta', 'Vuorinen, Tytti', 'Söderlund-Venermo, Maria', 'Vahlberg, Tero', 'Camargo, Carlos A.', 'Bochkov, Yury A.', 'Gern, James E.', 'Jartti, Tuomas']",,,,
,PMC,"Interplay between coronavirus, a cytoplasmic RNA virus, and nonsense-mediated mRNA decay pathway",http://dx.doi.org/10.1073/pnas.1811675115,PMC6205489,,,"Coronaviruses (CoVs), including severe acute respiratory syndrome CoV and Middle East respiratory syndrome CoV, are enveloped RNA viruses that carry a large positive-sense single-stranded RNA genome and cause a variety of diseases in humans and domestic animals. Very little is known about the host pathways that regulate the stability of CoV mRNAs, which carry some unusual features. Nonsense-mediated decay (NMD) is a eukaryotic RNA surveillance pathway that detects mRNAs harboring aberrant features and targets them for degradation. Although CoV mRNAs are of cytoplasmic origin, the presence of several NMD-inducing features (including multiple ORFs with internal termination codons that create a long 3′ untranslated region) in CoV mRNAs led us to explore the interplay between the NMD pathway and CoVs. Our study using murine hepatitis virus as a model CoV showed that CoV mRNAs are recognized by the NMD pathway as a substrate, resulting in their degradation. Furthermore, CoV replication induced the inhibition of the NMD pathway, and N protein (a viral structural protein) had an NMD inhibitory function that protected viral mRNAs from rapid decay. Our data further suggest that the NMD pathway interferes with optimal viral replication by degrading viral mRNAs early in infection, before sufficient accumulation of N protein. Our study presents clear evidence for the biological importance of the NMD pathway in controlling the stability of mRNAs and the efficiency of replication of a cytoplasmic RNA virus.",,"['Wada, Masami', 'Lokugamage, Kumari G.', 'Nakagawa, Keisuke', 'Narayanan, Krishna', 'Makino, Shinji']",,,,
,PMC,Viral etiological causes of febrile seizures for respiratory pathogens (EFES Study),http://dx.doi.org/10.1080/21645515.2018.1526588,PMC6422444,,,"Background: Febrile seizure is the most common childhood neurological disorder, is an important health problem with potential short- and long-term complications, also leading to economic burden and increased parental anxiety about fevers and seizures occurring in their children. There are no routine recommendation to detect etiological causes of FS for neurological perspective, further knowledge about the etiological causes of FS in children will support preventive measures and follow-up strategies. The aim of this study is to evaluate the percentage of respiratory viruses in children with FS. Methods: This prospective multicenter study, entitled “Viral etiological causes of febrile seizures for respiratory pathogens (EFES Study)” examined representative populations in eight different cities in Turkey between March 1, 2016 and April 1, 2017. Nasopharyngeal swabs were taken from all children at presentation. A respiratory multiplex array was performed to detect for influenza A and B; respiratory syncytial virus A and B; human parainfluenza virus 1-2-3 and 4; human coronavirus 229E and OC43; human rhinovirus; human enterovirus; human adenovirus; human bocavirus; human metapneumovirus. Results: During the study period, at least one virus was detected in 82.7% (144/174) of children with FS. The most frequently detected virus was adenovirus, followed by influenza A and influenza B. Detection of more than one virus was present in 58.3% of the children with FS, and the most common co-existence was the presence of adenovirus and influenza B. In children younger than 12 months, Coronavirus OC43 was the most common, while influenza A was most frequently observed in children older than 48 months (p < 0.05). Human bocavirus was common in children who experienced complex FS, while respiratory syncytial virus (RSV) A was more common in children who experienced simple FS. Influenza B virus was the most common virus identified in children who were experiencing their first incidence of FS (p < 0.05). Conclusions: This study indicates that respiratory viruses are important in the etiology of FS in children. The results show that antibiotics must be prescribed carefully in children with FS since the majority of cases are related to viral causes. Widespread use of the existing quadrivalent influenza vaccine might be useful for the prevention of FS related to the flu. Further vaccine candidates for potential respiratory pathogens, including RSV, might be helpful for the prevention of FS.",,"['Carman, Kursat Bora', 'Calik, Mustafa', 'Karal, Yasemin', 'Isikay, Sedat', 'Kocak, Ozan', 'Ozcelik, Aysima', 'Yazar, Ahmet Sami', 'Nuhoglu, Cagatay', 'Sag, Cigdem', 'Kilic, Omer', 'Dinleyici, Meltem', 'Lacinel Gurlevik, Sibel', 'Yimenicioglu, Sevgi', 'Ekici, Arzu', 'Perk, Peren', 'Tosun, Ayse', 'Isik, Ilhan', 'Yarar, Coskun', 'Arslantas, Didem', 'Dinleyici, Ener Cagri']",,,,
,PMC,Human Vaccines & Immunotherapeutics: News,http://dx.doi.org/10.1080/21645515.2018.1518064,PMC6183266,,,,,,,,,
,PMC,ISV Congress back to Europe,http://dx.doi.org/10.1080/21645515.2018.1518065,PMC6183265,,,,,"['Doolan, Denise L.', 'Lu, Shan']",,,,
,PMC,From APOBEC to ZAP: Diverse mechanisms used by cellular restriction factors to inhibit virus infections,http://dx.doi.org/10.1016/j.bbamcr.2018.09.012,PMC6334645,,,"Antiviral restriction factors are cellular proteins that inhibit the entry, replication, or spread of viruses. These proteins are critical components of the innate immune system and function to limit the severity and host range of virus infections. Here we review the current knowledge on the mechanisms of action of several restriction factors that affect multiple viruses at distinct stages of their life cycles. For example, APOBEC3G deaminates cytosines to hypermutate reverse transcribed viral DNA; IFITM3 alters membranes to inhibit virus membrane fusion; MXA/B oligomerize on viral protein complexes to inhibit virus replication; SAMHD1 decreases dNTP intracellular concentrations to prevent reverse transcription of retrovirus genomes; tetherin prevents release of budding virions from cells; Viperin catalyzes formation of a nucleoside analogue that inhibits viral RNA polymerases; and ZAP binds virus RNAs to target them for degradation. We also discuss countermeasures employed by specific viruses against these restriction factors, and mention secondary functions of several of these factors in modulating immune responses. These important examples highlight the diverse strategies cells have evolved to combat virus infections.",,"['Chemudupati, Mahesh', 'Kenney, Adam D.', 'Bonifati, Serena', 'Zani, Ashley', 'McMichael, Temet M.', 'Wu, Li', 'Yount, Jacob S.']",,,,
,PMC,"Case Report: Use of Plasma Exchange Followed by Convalescent Plasma Therapy in a Critically Ill Patient with Severe Fever and Thrombocytopenia Syndrome–Associated Encephalopathy: Cytokine/Chemokine Concentrations, Viral Loads, and Antibody Responses",http://dx.doi.org/10.4269/ajtmh.17-0766,PMC6283494,,,"We describe the case of a patient with severe fever with thrombocytopenia syndrome (SFTS) complicated by SFTS-associated encephalopathy who was successfully treated with 4-day plasma exchange followed by two-time convalescent plasma therapy. During plasma exchange, the plasma cytokines interferon-α and inducible protein-10 gradually decreased without change of plasma viral load. However, plasma viral load gradually decreased after convalescent plasma therapy. This case provides important insights for understanding the mechanisms of experimental therapy in severely affected SFTS patients.",,"['Choi, Sungim', 'Kim, Min-Chul', 'Kwon, Ji-Soo', 'Kim, Ji-Yeun', 'Lee, Keun Hwa', 'Kim, Sung-Han']",,,,
,PMC,Clinical characteristics and outcomes of human rhinovirus positivity in hospitalized children,http://dx.doi.org/10.4103/atm.ATM_291_17,PMC6196663,30416595,CC BY-NC-SA,"BACKGROUND: The clinical relevance of positive human rhinovirus (HRV) in hospitalized patients is unclear. Our objective was to describe the clinical characteristics and outcomes of HRV positivity in a heterogeneous population of hospitalized children, compared to those positive for another respiratory virus and those where no respiratory virus was detected. METHODS: A retrospective case–control study of children hospitalized between January 2014 to April 2015 who had a respiratory viral specimen collected. Clinical and laboratory data were collected, and baseline characteristics and clinical variables were compared. RESULTS: During the study period, there were 671 specimens obtained from 577 patients that were processed for the respiratory viral polymerase chain reaction assay, of which 198 were positive for HRV, 167 positive for another respiratory virus, and 306 where no respiratory virus was detected. A history of asthma was significantly associated with HRV-positive patients (odds ratio [OR] 3.71; P < 0.001). On multivariate analysis, HRV-positive patients had a higher requirement for mechanical ventilation (OR 1.44), lower rates of readmission (OR 0.53), and lower mortality (OR 0.35) compared to patients with no respiratory virus isolated; however, none were statistically significant. HRV-positive patients did have a significantly shorter length of stay (LOS) compared with patients with no respiratory virus isolated (difference–0.35; P = 0.001). Similar outcomes were seen in patients positive for other respiratory viruses. CONCLUSIONS: HRV-positive hospitalized pediatric patients with a heterogeneous set of clinical diagnoses had higher association with asthma compared to patients who had another, or no, respiratory virus isolated. HRV-positive patients had shorter LOS compared to patients who had no respiratory viruses isolated. These findings suggest that HRV positivity in hospitalized pediatric patients may not lead to adverse clinical outcomes, although asthma is a risk factor regardless of clinical comorbidities and diagnoses. Further research is warranted to understand the predisposition of asthma to HRV positivity.",2018 Oct-Dec,"['Tam, Pui-Ying Iroh', 'Zhang, Lei', 'Cohen, Zohara']",Ann Thorac Med,,,
,PMC,Alkyl-imino sugars inhibit the pro-oncogenic ion channel function of human papillomavirus (HPV) E5,http://dx.doi.org/10.1016/j.antiviral.2018.08.005,PMC6156294,30096339,CC BY,"Despite the availability of prophylactic vaccines the burden of human papillomavirus (HPV) associated malignancy remains high and there is a need to develop additional therapeutic strategies to complement vaccination. We have previously shown that the poorly characterised E5 oncoprotein forms a virus-coded ion channel or viroporin that was sensitive to the amantadine derivative rimantadine. We now demonstrate that alkylated imino sugars, which have antiviral activity against a number of viruses, inhibit E5 channel activity in vitro. Using molecular modelling we predict that imino sugars intercalate between E5 protomers to prevent channel oligomerisation. We explored the ability of these viroporin inhibitors to block E5-mediated activation of mitogenic signalling in keratinocytes. Treatment with either rimantadine or imino sugars prevented ERK-MAPK phosphorylation and reduced cyclin B1 expression in cells expressing E5 from a number of high-risk HPV types. Moreover, viroporin inhibitors also reduced ERK-MAPK activation and cyclin B1 expression in differentiating primary human keratinocytes containing high-risk HPV18. These observations provide evidence of a key role for E5 viroporin function during the HPV life cycle. Viroporin inhibitors could be utilised for stratified treatment of HPV associated tumours prior to virus integration, or as true antiviral therapies to eliminate virus prior to malignant transformation.",2018 Oct,"['Wetherill, Laura F.', 'Wasson, Christopher W.', 'Swinscoe, Gemma', 'Kealy, David', 'Foster, Richard', 'Griffin, Stephen', 'Macdonald, Andrew']",Antiviral Res,,,
,PMC,Preclinical efficacy in therapeutic area guidelines from the U.S. Food and Drug Administration and the European Medicines Agency: a cross‐sectional study,http://dx.doi.org/10.1111/bph.14485,PMC6193882,,,"BACKGROUND AND PURPOSE: Therapeutic area guidelines (TAGs) published by the EMA and the FDA offer guidance in planning the launch of a trial in a certain indication. We assessed and compared the guidance on preclinical efficacy of all available TAGs from EMA and FDA. EXPERIMENTAL APPROACH: EMA and FDA websites and databases were searched for all TAGs. A mixed deductive and inductive approach was applied to analyse and cluster content for preclinical efficacy. KEY RESULTS: A total of 114 EMA and 120 FDA TAGs were identified, covering 126 indications. Our core finding is that 75% of EMA TAGs and 58% from the FDA TAGs do not offer any guidance on preclinical efficacy. TAGs varied widely on the extent, nature and detail of guidance. CONCLUSIONS AND IMPLICATIONS: Guidance on preclinical efficacy in a consistent, comprehensive and explicit way that still allows for justified deviations is an important but neglected aspect of transparency for drug development. This transparency would help sponsors in designing preclinical studies and in negotiating more efficiently with regulators.",,"['Langhof, Holger', 'Chin, William Wei Lim', 'Wieschowski, Susanne', 'Federico, Carole', 'Kimmelman, Jonathan', 'Strech, Daniel']",,,,
,PMC,Breeding Characteristics and Dose-dependent Blood Pressure Responses of Transgenic Cyp1a1–Ren2 Rats,http://dx.doi.org/10.30802/AALAS-CM-17-18000026,PMC6200032,,,"Hypertension is a leading risk factor for cardiovascular and chronic kidney disease. A new rodent model (transgenic male Cyp1a1–Ren2 rats) provides reversible induction of hypertension through the addition of indole-3-carbinol (I3C) to the diet, without the need for surgical intervention, thus giving researchers control over both the onset of hypertension and its magnitude (I3C dose-dependency). We here report the breeding performance and productivity of Cyp1a1–Ren2 rats. Despite being transgenic, these animals proved to be efficient breeders. In addition to confirming inducible and reversible dose-dependent hypertension (by using I3C doses of 0.125%, 0.167%, and 0.25% [w/w] in the diet for 14 d, followed by normal chow for 4 d), we demonstrated that hypertension can be sustained chronically (14 wk) by continuous dosing with I3C (0.167% [w/w]) in the diet. In chronically dosed male rats, systolic blood pressure continued to rise, from 173 ± 11 mm Hg after 1 mo to 196 ± 19 mm Hg after 3 mo, with no adverse phenotypic features observed. In conclusion, Cyp1a1–Ren2 rats are a useful animal model to investigate hypertension-induced end-organ damage and potential new therapeutic targets to manage hypertension.",,"['Leader, Catherine J', 'Clark, Barbara J', 'Hannah, Amber R', 'Sammut, Ivan A', 'Wilkins, Gerard T', 'Walker, Robert J']",,,,
,PMC,Allograft Inflammatory Factor 1 as an Immunohistochemical Marker for Macrophages in Multiple Tissues and Laboratory Animal Species,http://dx.doi.org/10.30802/AALAS-CM-18-000017,PMC6200031,,,"Allograft inflammatory factor 1 (AIF1) is a commonly used marker for microglia in the brains of humans and some animal models but has had limited applications elsewhere. We sought to determine whether AIF1 can be used as a macrophage marker across common laboratory animal species and tissues. We studied tissues (that is, spleen, liver, and lung) with defined macrophage populations by using an AIF1 immunostaining technique previously validated in human tissue. Tissues were collected from various mouse strains (n = 20), rat strains (n = 15), pigs (n = 4), ferrets (n = 4), and humans (n = 4, lung only). All samples of liver had scattered immunostaining in interstitial cells, consistent with resident tissue macrophages (Kupffer cells). Spleen samples had cellular immunostaining of macrophages in both the red and white pulp compartments, but the red pulp had more immunostained cellular aggregates and, in some species, increased immunostaining intensity compared with white pulp. In lung, alveolar macrophages had weak to moderate staining, whereas interstitial and perivascular macrophages demonstrated moderate to robust staining. Incidental lesions and tissue changes were detected in some sections, including a tumor, inducible bronchus-associated lymphoid tissue, and inflammatory lesions that demonstrated AIF1 immunostaining of macrophages. Finally, we compared AIF1 immunostaining of alveolar macrophages between a hypertensive rat model (SHR strain) and a normotensive model (WKY strain). SHR lungs had altered intensity and distribution of immunostaining in activated macrophages compared with macrophages of WKY lungs. Overall, AIF1 immunostaining demonstrated reproducible macrophage staining across multiple species and tissue types. Given the increasing breadth of model species used to study human disease, the use of cross-species markers and techniques can reduce some of the inherent variability within translational research.",,"['Donovan, Kathleen M', 'Leidinger, Mariah R', 'McQuillen, Logan P', 'Goeken, J Adam', 'Hogan, Christine M', 'Harwani, Sailesh C', 'Flaherty, Heather A', 'Meyerholz, David K']",,,,
,PMC,Synthetic genomics: a new venture to dissect genome fundamentals and engineer new functions,http://dx.doi.org/10.1016/j.cbpa.2018.04.002,PMC6351456,29751161,CC BY,"Since the first synthetic gene was synthesized in 1970s, the efficiency and the capacity of made-to-order DNA sequence synthesis has increased by several orders of magnitude. Advances in DNA synthesis and assembly over the past years has resulted in a steep drop in price for custom made DNA. Similar effects were observed in DNA sequencing technologies which underpin DNA-reading projects. Today, synthetic DNA sequences with more than 10 000 bps and turn-around times of a few weeks are commercially available. This enables researchers to perform large-scale projects to write synthetic chromosomes and characterize their functionalities in vivo. Synthetic genomics opens up new paradigms to study the genome fundamentals and engineer novel biological functions.",2018 Oct,"['Schindler, Daniel', 'Dai, Junbiao', 'Cai, Yizhi']",Curr Opin Chem Biol,,,
,PMC,State of the Globe: Ensuring Effective Communication in Public Health Emergencies,http://dx.doi.org/10.4103/jgid.jgid_60_18,PMC6276321,30581255,CC BY-NC-SA,,2018 Oct-Dec,"Raina, Sunil Kumar",J Glob Infect Dis,,,
,PMC,Studying Communication Problems for Emergency Management of SARS and H7N9 in China,http://dx.doi.org/10.4103/jgid.jgid_168_17,PMC6276313,30581257,CC BY-NC-SA,"BACKGROUND: Severe Acute Respiratory Syndrome (SARS) and Influenza A virus Subtype H7N9 (H7N9) have both had a great impact on China in the 21(st) century, causing significant negative impacts on health, the economy, and even global security. The control efforts for SARS were heavily criticized, the H7N9 response, 10 years later was acknowledged to be much better. AIMS: This article explores communication for emergency management of SARS in 2003 and H7N9 in 2013 in China, to provide useful evidence for government and practitioner on management improvement for infectious disease outbreaks response in China and international community in the future. METHODS: This study uses a qualitative case study approach, including in-depth interviews, literature review, and document, to analysis the emergency management of SARS in 2003 and H7N9 in 2013 in China, identified the problems of communication with the emergency management process for SARS and H7N9. RESULTS: The control efforts for SARS were slow to be mobilized and were heavily criticized and generally considered to be suboptimal, as the poor handling of SARS exposed serious communication problems in the then emergency management system processes. The H7N9 response, 10 years later, was acknowledged to be much better. CONCLUSION: Communication is very important in the prevention and control of infectious diseases. From SARS to H7N9, the progress had been made in information disclosure.",2018 Oct-Dec,"['Qiu, Wuqi', 'Chu, Cordia', 'Mao, Ayan', 'Wu, Jing']",J Glob Infect Dis,,,
,PMC,Bilateral massive pneumonia as an unusual manifestation of Puumala hantavirus infection,http://dx.doi.org/10.4103/jpgm.JPGM_283_17,PMC6198694,30136660,CC BY-NC-SA,"Renal involvement due to European Puumala virus (PUUV) is frequent but pulmonary involvement is quite rare. We present here, a 24-year-old male with atypical clinical presentation of acute PUUV infection with gross pulmonary and minimal renal involvement. Severe pulmonary manifestations of PUUV infection, in this case, highlights that hantavirus infection should be considered in the differential diagnosis of atypical pneumonia.",2018 Oct-Dec,"['Gözdaş, HT', 'Menemenlioğlu, D', 'Coşgun, Y', 'Çelebi, G']",J Postgrad Med,,,
,PMC,"Inhalation lung injury induced by smoke bombs in children: CT manifestations, dynamic evolution features and quantitative analysis",http://dx.doi.org/10.21037/jtd.2018.09.84,PMC6236165,,,"BACKGROUND: This retrospective study aimed to investigate the computed tomography (CT) manifestations, short-term dynamic evolution features and quantitative lung CT analysis of inhalation lung injury induced by smoke bomb flare. METHODS: Eleven pediatric patients (aged 11 to 13) who inhaled the smoke of smoke bombs underwent several low-dose chest CT scans. The image characteristics and their dynamic changes were observed and quantitative CT values were analyzed. The quantitative CT indicators included lung injury CT score (LICTS), lung fibrosis CT score (LFCTS), mean lung density (MLD), normally aerated volume ratio (NAVR) and reductively aerated volume ratio (RAVR). Box-plot was used to analyze the dynamic changes of each indicator and Spearman statistical method was used to analyze the correlation between any two indicators. RESULTS: (I) In most cases, there were multiple consolidation and massive ground-glass opacities (GGOs) in the two lungs, which aggravated in the early stage and then gradually dissoluted in the later stage. LICTS was positively correlated with MLD (r=0.811, P=0.000), while it was negatively correlated with NAVR (r=−0.712, P=0.000). There existed interstitial fibrosis in the later stage, and LFCTS was positively correlated with RAVR (r=0.382, P=0.028). (II) In one case, the patterns were like layered cake, i.e., consolidation with air bronchus signs in the accumulation area, GGOs in the aforementioned area and normal lung in the top area. The patterns aggravated in the early stage and quickly dissolved in the later stage, and only a few residual fibrotic lesions existed on the final scan. (III) For severe cases, pneumomediastinum and subcutaneous emphysema aggravated in the early stage and then gradually dissolved in the later stage. CONCLUSIONS: The chest CT manifestations of inhalation lung injury induced by smoke bombs are predominantly GGOs and consolidation. They aggravate in the early stage and gradual dissolute in the later stage. CT quantitative values can contribute to evaluating the extent of this disease, and NAVR and RAVR can be used to assess pulmonary function.",,"['Ma, Yaqiong', 'Zhang, Shikui', 'Zhao, Lianping', 'Zhou, Xing', 'Mao, Zeqing', 'Xu, Huaxin', 'Ru, Xiaorui', 'Huang, Gang']",,,,
,PMC,Glycyrrhizic acid activates chicken macrophages and enhances their Salmonella-killing capacity in vitro,http://dx.doi.org/10.1631/jzus.B1700506,PMC6194354,,,"Objective: Salmonella enterica remains a major cause of food-borne disease in humans, and Salmonella Typhimurium (ST) contamination of poultry products is a worldwide problem. Since macrophages play an essential role in controlling Salmonella infection, the aim of this study was to evaluate the effect of glycyrrhizic acid (GA) on immune function of chicken HD11 macrophages. Methods: Chicken HD11 macrophages were treated with GA (0, 12.5, 25, 50, 100, 200, 400, or 800 μg/ml) and lipopolysaccharide (LPS, 500 ng/ml) for 3, 6, 12, 24, or 48 h. Evaluated responses included phagocytosis, bacteria-killing, gene expression of cell surface molecules (cluster of differentiation 40 (CD40), CD80, CD83, and CD197) and antimicrobial effectors (inducible nitric oxide synthase (iNOS), NADPH oxidase-1 (NOX-1), interferon-γ (IFN-γ), LPS-induced tumor necrosis factor (TNF)-α factor (LITAF), interleukin-6 (IL-6), and IL-10), and production of nitric oxide (NO) and hydrogen peroxide (H(2)O(2)). Results: GA increased the internalization of both fluorescein isothiocyanate (FITC)-dextran and ST by HD11 cells and markedly decreased the intracellular survival of ST. We found that the messenger RNA (mRNA) expression of cell surface molecules (CD40, CD80, CD83, and CD197) and cytokines (IFN-γ, IL-6, and IL-10) of HD11 cells was up-regulated following GA exposure. The expression of iNOS and NOX-1 was induced by GA and thereby the productions of NO and H(2)O(2) in HD11 cells were enhanced. Notably, it was verified that nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathways were responsible for GA-induced synthesis of NO and IFN-γ gene expression. Conclusions: Taken together, these results suggested that GA exhibits a potent immune regulatory effect to activate chicken macrophages and enhances Salmonella-killing capacity.",,"['Wang, Bai-kui', 'Mao, Yu-long', 'Gong, Li', 'Xu, Xin', 'Jiang, Shou-qun', 'Wang, Yi-bing', 'Li, Wei-fen']",,,,
,PMC,"Always ready, always prepared—preparing for the next pandemic",http://dx.doi.org/10.21037/tp.2018.09.06,PMC6212382,,,"A future global pandemic is likely to occur and planning for the care of critically ill children is less robust than that for adults. This review covers the current state of federal and regional resources for pediatric care in pandemics, a strategy for pandemic preparation in pediatric intensive care units and regions focusing on stuff, space, staff and systems, considerations in developing surge capacity and triage protocols, special circumstances such as highly infectious and highly lethal pandemics, and a discussion of ethics in the setting of pediatric critical care in a pandemic.",,"['Hamele, Mitchell', 'Neumayer, Katie', 'Sweney, Jill', 'Poss, W. Bradley']",,,,
,PMC,Insertion position as well as the inserted TRS and gene sequences differentially affect the retention of foreign gene expression by simian hemorrhagic fever virus (SHFV),http://dx.doi.org/10.1016/j.virol.2018.09.014,PMC6294337,,,"Recombinant SHFV infectious cDNA clones expressing a foreign gene from an additional sg mRNA were constructed. Two 3′ genomic region sites, between ORF4′ and ORF2b and between ORF4 and ORF5, were utilized for insertion of the myxoma M013 gene with a C-terminal V5 tag followed by one of the three inserted transcription regulatory sequences (TRS), TRS2′, TRS4′ or TRS7. M013 insertion at the ORF4′/ORF2b site but not the ORF4/ORF5 site generated progeny virus but only recombinant viruses with an inserted TRS2′ retained the entire M013 gene through passage four. Insertion of an auto-fluorescent protein gene, iLOV, with an inserted TRS2′ at the ORF4′/ORF2b site generated viable progeny virus and iLOV expression was maintained through passage eight. Although regulation of SHFV subgenomic RNA synthesis is complex, the ORF4′/ORF2b site, which is located between the two sets of minor structural proteins, is able to tolerate foreign gene insertion.",,"['Di, Han', 'Morantz, Esther K.', 'Sadhwani, Heena', 'Madden, Joseph C.', 'Brinton, Margo A.']",,,,
,PMC,Identification and characterization of the myeloid differentiation factor 88 gene in yellow catfish,http://dx.doi.org/10.1007/s13205-018-1448-z,PMC6163110,,,"Myeloid differentiation factor 88 (MyD88) is an important adapter protein of the innate immune system, but it has never before been reported in yellow catfish (Pelteobagrus fulvidraco). In this study, we cloned and characterized the yellow catfish MyD88 gene. The gene was 1230 bp in length and contained an 876-bp open reading frame which encodes a polypeptide of 291 amino acid residues. The theoretical molecular mass and isoelectric point of this polypeptide were 33.4341 kDa and 5.17, respectively. Furthermore, bioinformatic and phylogenetic analyses grouped yellow catfish MyD88 with MyD88 of other fish. We found that the deduced amino acid sequence showed that the conserved N-terminal death domain and the C-terminal typical Toll/interleukin-1 receptor domain were very similar to those of other fish. Moreover, reverse transcription PCR showed that yellow catfish MyD88 is ubiquitously expressed in all tissues examined, with highest expression levels observed in the spleen and lowest levels in the intestine. Importantly, MyD88 was shown to be significantly up-regulated in the intestines after 30-day dietary supplement of Clostridium butyricum. Collectively, these results indicate that yellow catfish MyD88 has a conserved structure and is probably an important component of innate immunity in yellow catfish. This study is the first to identify and characterize MyD88 in yellow catfish, thereby providing a reference for further research into the yellow catfish innate immune system.",,"['Yu, Lintian', 'Zhang, Long', 'Yang, Hua', 'Gui, Guohong', 'Liu, Yiping', 'Xiao, Yingping']",,,,
,PMC,Nucleotide triphosphatase and RNA chaperone activities of murine norovirus NS3,http://dx.doi.org/10.1099/jgv.0.001151,PMC7011751,,,"Modulation of RNA structure is essential in the life cycle of RNA viruses. Immediate replication upon infection requires RNA unwinding to ensure that RNA templates are not in intra- or intermolecular duplex forms. The calicivirus NS3, one of the highly conserved nonstructural (NS) proteins, has conserved motifs common to helicase superfamily 3 among six genogroups. However, its biological functions are not fully understood. In this study we report the oligomeric state and the nucleotide triphosphatase (NTPase) and RNA chaperone activities of the recombinant full-length NS3 derived from murine norovirus (MNV). The MNV NS3 has an Mg(2+)-dependent NTPase activity, and site-directed mutagenesis of the conserved NTPase motifs blocked enzyme activity and viral replication in cells. Further, the NS3 was found via fluorescence resonance energy transfer (FRET)-based assays to destabilize double-stranded RNA in the presence of Mg(2+) or Mn(2+) in an NTP-independent manner. However, the RNA destabilization activity was not affected by mutagenesis of the conserved motifs of NTPase. These results reveal that the MNV NS3 has an NTPase-independent RNA chaperone-like activity, and that a FRET-based RNA destabilization assay has the potential to identify new antiviral drugs targeting NS3.",,"['Han, Kang Rok', 'Lee, Ji-Hye', 'Kotiguda, Giri Gowda', 'Jung, Kyoung Ho', 'Chung, Mi Sook', 'Kang, Soowon', 'Hwang, Seungmin', 'Kim, Kyung Hyun']",,,,
,PMC,Recurring and Emerging Questions Related to Management of HIV-Related Opportunistic Infections,,PMC6291295,,,"The incidence of HIV-related opportunistic infections (OIs) has dramatically declined with the ability to achieve viral suppression and immune reconstitution with potent antiretroviral therapy. However, a large number of patients remain at risk for OIs because they are diagnosed at late stages of HIV disease, fail to stay in treatment, or fail to maintain viral suppression. Clinicians should remain vigilant for OIs and for changes in recommended management strategies. Issues that often arise in this regard include how to interpret polymerase chain reaction diagnostic results in individuals with HIV infection; whether primary prophylaxis for Mycobacterium avium complex is still needed; whether clinicians should screen asymptomatic patients for cryptococcal antigen; and need for amphotericin B in treatment regimens for cryptococcal meningitis. This article summarizes a presentation by Henry Masur, MD, at the IAS–USA continuing education program held in Washington, DC, in April 2018.",,"Masur, Henry",,,,
,PMC,ECDC’s latest publications,http://dx.doi.org/10.2807/1560-7917.ES.2018.23.39.1809272,PMC6169200,,CC BY,,2018 Sep 27,,Euro Surveill,,,
,PMC,Elevated Human Dipeptidyl Peptidase 4 Expression Reduces the Susceptibility of hDPP4 Transgenic Mice to Middle East Respiratory Syndrome Coronavirus Infection and Disease,http://dx.doi.org/10.1093/infdis/jiy574,PMC6376904,,,"BACKGROUND: The ongoing Middle East respiratory syndrome coronavirus (MERS-CoV) infections pose threats to public health worldwide, making an understanding of MERS pathogenesis and development of effective medical countermeasures (MCMs) urgent. METHODS: We used homozygous (+/+) and heterozygous (+/−) human dipeptidyl peptidase 4 (hDPP4) transgenic mice to study the effect of hDPP4 on MERS-CoV infection. Specifically, we determined values of 50% lethal dose (LD(50)) of MERS-CoV for the 2 strains of mice, compared and correlated their levels of soluble (s)hDPP4 expression to susceptibility, and explored recombinant (r)shDPP4 as an effective MCM for MERS infection. RESULTS: hDPP4(+/+) mice were unexpectedly more resistant than hDPP4(+/−) mice to MERS-CoV infection, as judged by increased LD(50), reduced lung viral infection, attenuated morbidity and mortality, and reduced histopathology. Additionally, the resistance to MERS-CoV infection directly correlated with increased serum shDPP4 and serum virus neutralizing activity. Finally, administration of rshDPP4 led to reduced lung virus titer and histopathology. CONCLUSIONS: Our studies suggest that the serum shDPP4 levels play a role in MERS pathogenesis and demonstrate a potential of rshDPP4 as a treatment option for MERS. Additionally, it offers a validated pair of Tg mice strains for characterizing the effect of shDPP4 on MERS pathogenesis.",,"['Algaissi, Abdullah', 'Agrawal, Anurodh S', 'Han, Song', 'Peng, Bi-Hung', 'Luo, Chuming', 'Li, Fang', 'Chan, Teh-Sheng', 'Couch, Robert B', 'Tseng, Chien-Te K']",,,,
,PMC,The HIV Integrase Inhibitor Raltegravir Inhibits Felid Alphaherpesvirus 1 Replication by Targeting both DNA Replication and Late Gene Expression,http://dx.doi.org/10.1128/JVI.00994-18,PMC6158441,,,"Alphaherpesvirus-associated ocular infections in humans caused by human alphaherpesvirus 1 (HHV-1) remain challenging to treat due to the frequency of drug application required and the potential for the selection of drug-resistant viruses. Repurposing on-the-market drugs is a viable strategy to accelerate the pace of drug development. It has been reported that the human immunodeficiency virus (HIV) integrase inhibitor raltegravir inhibits HHV-1 replication by targeting the DNA polymerase accessory factor and limits terminase-mediated genome cleavage of human betaherpesvirus 5 (HHV-5). We have previously shown, both in vitro and in vivo, that raltegravir can also inhibit the replication of felid alphaherpesvirus 1 (FeHV-1), a common ocular pathogen of cats with a pathogenesis similar to that of HHV-1 ocular disease. In contrast to what was reported for HHV-1, we were unable to select for a raltegravir-resistant FeHV-1 strain in order to define any basis for drug action. A candidate-based approach to explore the mode of action of raltegravir against FeHV-1 showed that raltegravir did not impact FeHV-1 terminase function, as described for HHV-5. Instead, raltegravir inhibited DNA replication, similarly to HHV-1, but by targeting the initiation of viral DNA replication rather than elongation. In addition, we found that raltegravir specifically repressed late gene expression independently of DNA replication, and both activities are consistent with inhibition of ICP8. Taken together, these results suggest that raltegravir could be a valuable therapeutic agent against herpesviruses. IMPORTANCE The rise of drug-resistant herpesviruses is a longstanding concern, particularly among immunocompromised patients. Therefore, therapies targeting viral proteins other than the DNA polymerase that may be less likely to lead to drug-resistant viruses are urgently needed. Using FeHV-1, an alphaherpesvirus closely related to HHV-1 that similarly causes ocular herpes in its natural host, we found that the HIV integrase inhibitor raltegravir targets different stages of the virus life cycle beyond DNA replication and that it does so without developing drug resistance under the conditions tested. This shows that the drug could provide a viable strategy for the treatment of herpesvirus infections.",,"['Pennington, Matthew R.', 'Voorhees, Ian E. H.', 'Callaway, Heather M.', 'Dehghanpir, Shannon D.', 'Baines, Joel D.', 'Parrish, Colin R.', 'Van de Walle, Gerlinde R.']",,,,
,PMC,"Inhibition of Stress Granule Formation by Middle East Respiratory Syndrome Coronavirus 4a Accessory Protein Facilitates Viral Translation, Leading to Efficient Virus Replication",http://dx.doi.org/10.1128/JVI.00902-18,PMC6158436,,,"Stress granule (SG) formation is generally triggered as a result of stress-induced translation arrest. The impact of SG formation on virus replication varies among different viruses, and the significance of SGs in coronavirus (CoV) replication is largely unknown. The present study examined the biological role of SGs in Middle East respiratory syndrome (MERS)-CoV replication. The MERS-CoV 4a accessory protein is known to inhibit SG formation in cells in which it was expressed by binding to double-stranded RNAs and inhibiting protein kinase R (PKR)-mediated phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α). Replication of MERS-CoV lacking the genes for 4a and 4b (MERS-CoV-Δp4), but not MERS-CoV, induced SG accumulation in MERS-CoV-susceptible HeLa/CD26 cells, while replication of both viruses failed to induce SGs in Vero cells, demonstrating cell type-specific differences in MERS-CoV-Δp4-induced SG formation. MERS-CoV-Δp4 replicated less efficiently than MERS-CoV in HeLa/CD26 cells, and inhibition of SG formation by small interfering RNA-mediated depletion of the SG components promoted MERS-CoV-Δp4 replication, demonstrating that SG formation was detrimental for MERS-CoV replication. Inefficient MERS-CoV-Δp4 replication was not due to either the induction of type I and type III interferons or the accumulation of viral mRNAs in the SGs. Rather, it was due to the inefficient translation of viral proteins, which was caused by high levels of PKR-mediated eIF2α phosphorylation and likely by the confinement of various factors that are required for translation in the SGs. Finally, we established that deletion of the 4a gene alone was sufficient for inducing SGs in infected cells. Our study revealed that 4a-mediated inhibition of SG formation facilitates viral translation, leading to efficient MERS-CoV replication. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory failure with a high case fatality rate in patients, yet effective antivirals and vaccines are currently not available. Stress granule (SG) formation is one of the cellular stress responses to virus infection and is generally triggered as a result of stress-induced translation arrest. SGs can be beneficial or detrimental for virus replication, and the biological role of SGs in CoV infection is unclear. The present study showed that the MERS-CoV 4a accessory protein, which was reported to block SG formation in cells in which it was expressed, inhibited SG formation in infected cells. Our data suggest that 4a-mediated inhibition of SG formation facilitates the translation of viral mRNAs, resulting in efficient virus replication. To our knowledge, this report is the first to show the biological significance of SG in CoV replication and provides insight into the interplay between MERS-CoV and antiviral stress responses.",,"['Nakagawa, Keisuke', 'Narayanan, Krishna', 'Wada, Masami', 'Makino, Shinji']",,,,
,PMC,Substrate Binding by the Second Sialic Acid-Binding Site of Influenza A Virus N1 Neuraminidase Contributes to Enzymatic Activity,http://dx.doi.org/10.1128/JVI.01243-18,PMC6158415,,,"The influenza A virus (IAV) neuraminidase (NA) protein plays an essential role in the release of virus particles from cells and decoy receptors. The NA enzymatic activity presumably needs to match the activity of the IAV hemagglutinin (HA) attachment protein and the host sialic acid (SIA) receptor repertoire. We analyzed the enzymatic activities of N1 NA proteins derived from avian (H5N1) and human (H1N1) IAVs and analyzed the role of the second SIA-binding site, located adjacent to the conserved catalytic site, therein. SIA contact residues in the second SIA-binding site of NA are highly conserved in avian, but not human, IAVs. All N1 proteins preferred cleaving α2,3- over α2,6-linked SIAs even when their corresponding HA proteins displayed a strict preference for α2,6-linked SIAs, indicating that the specificity of the NA protein does not need to fully match that of the corresponding HA protein. NA activity was affected by substitutions in the second SIA-binding site that are observed in avian and human IAVs, at least when multivalent rather than monovalent substrates were used. These mutations included both SIA contact residues and residues that do not directly interact with SIA in all three loops of the second SIA-binding site. Substrate binding via the second SIA-binding site enhanced the catalytic activity of N1. Mutation of the second SIA-binding site was also shown to affect virus replication in vitro. Our results indicate an important role for the N1 second SIA-binding site in binding to and cleavage of multivalent substrates. IMPORTANCE Avian and human influenza A viruses (IAVs) preferentially bind α2,3- and α2,6-linked sialic acids (SIAs), respectively. A functional balance between the hemagglutinin (HA) attachment and neuraminidase (NA) proteins is thought to be important for host tropism. What this balance entails at the molecular level is, however, not well understood. We now show that N1 proteins of both avian and human viruses prefer cleaving avian- over human-type receptors although human viruses were relatively better in cleavage of the human-type receptors. In addition, we show that substitutions at different positions in the second SIA-binding site found in NA proteins of human IAVs have a profound effect on binding and cleavage of multivalent, but not monovalent, receptors and affect virus replication. Our results indicate that the HA-NA balance can be tuned via modification of substrate binding via this site and suggest an important role of the second SIA-binding site in host tropism.",,"['Du, Wenjuan', 'Dai, Meiling', 'Li, Zeshi', 'Boons, Geert-Jan', 'Peeters, Ben', 'van Kuppeveld, Frank J. M.', 'de Vries, Erik', 'de Haan, Cornelis A. M.']",,,,
,PMC,Nonsteroidal Anti-inflammatory Drugs Potently Inhibit the Replication of Zika Viruses by Inducing the Degradation of AXL,http://dx.doi.org/10.1128/JVI.01018-18,PMC6158411,,,"Zika virus (ZIKV) is genetically and biologically related to other Flaviviridae family members and has disseminated to many countries. It is associated with severe consequences, including the abnormal development of the neural system in fetuses and neurological diseases in adults. Therefore, the development of anti-ZIKV drugs is of paramount importance. Screening of generic drugs revealed that several nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, ibuprofen, naproxen, acetaminophen, and lornoxicam, potently inhibited the entry of Zika virus Env/HIV-1-pseudotyped viruses. They also significantly inhibited the replication of wild-type ZIKV both in cell lines and in primary human fetal endothelial cells. Interestingly, the NSAIDs exerted this inhibitory effect by potently reducing the expression of AXL, the entry cofactor of ZIKV. Further studies showed that the NSAIDs downregulated the prostaglandin E(2)/prostaglandin E receptor 2 (EP2)/cAMP/protein kinase A (PKA) signaling pathway and reduced PKA-dependent CDC37 phosphorylation and the interaction between CDC37 and HSP90, which subsequently facilitated CHIP/ubiquitination/proteasome-mediated AXL degradation. Taken together, our results highlight a new mechanism of action of antiviral agents which may assist in designing a convenient strategy for treating ZIKV-infected patients. IMPORTANCE Zika virus (ZIKV) infection, which causes congenital malformations, including microcephaly and other neurological disorders, has attracted global attention. We observed that several NSAIDs significantly inhibited ZIKV infection. Based on our observations, we propose a novel mechanism of action of antiviral compounds which involves the blockade of virus entry via degradation of the entry cofactor. Furthermore, NSAIDs can be practically used for preventing ZIKV infection in pregnant women, as certain NSAIDs, including ibuprofen and acetaminophen, are considered clinically safe.",,"['Pan, Ting', 'Peng, Zhilin', 'Tan, Likai', 'Zou, Fan', 'Zhou, Nan', 'Liu, Bingfeng', 'Liang, Liting', 'Chen, Cancan', 'Liu, Jun', 'Wu, Liyang', 'Liu, Guangyan', 'Peng, Zhiqin', 'Liu, Weiwei', 'Ma, Xiancai', 'Zhang, Junsong', 'Zhu, Xun', 'Liu, Ting', 'Li, Mengfeng', 'Huang, Xi', 'Tao, Liang', 'Zhang, Yiwen', 'Zhang, Hui']",,,,
,PMC,Contribution of a Multifunctional Polymerase Region of Foot-and-Mouth Disease Virus to Lethal Mutagenesis,http://dx.doi.org/10.1128/JVI.01119-18,PMC6158410,,,"Viral RNA-dependent RNA polymerases (RdRps) are major determinants of high mutation rates and generation of mutant spectra that mediate RNA virus adaptability. The RdRp of the picornavirus foot-and-mouth disease virus (FMDV), termed 3D, is a multifunctional protein that includes a nuclear localization signal (NLS) in its N-terminal region. Previous studies documented that some amino acid substitutions within the NLS altered nucleotide recognition and enhanced the incorporation of the mutagenic purine analogue ribavirin in viral RNA, but the mutants tested were not viable and their response to lethal mutagenesis could not be studied. Here we demonstrate that NLS amino acid substitution M16A of FMDV serotype C does not affect infectious virus production but accelerates ribavirin-mediated virus extinction. The mutant 3D displays polymerase activity, RNA binding, and copying processivity that are similar to those of the wild-type enzyme but shows increased ribavirin-triphosphate incorporation. Crystal structures of the mutant 3D in the apo and RNA-bound forms reveal an expansion of the template entry channel due to the replacement of the bulky Met by Ala. This is a major difference with other 3D mutants with altered nucleotide analogue recognition. Remarkably, two distinct loop β9-α11 conformations distinguish 3Ds that exhibit higher or lower ribavirin incorporation than the wild-type enzyme. This difference identifies a specific molecular determinant of ribavirin sensitivity of FMDV. Comparison of several polymerase mutants indicates that different domains of the molecule can modify nucleotide recognition and response to lethal mutagenesis. The connection of this observation with current views on quasispecies adaptability is discussed. IMPORTANCE The nuclear localization signal (NLS) of the foot-and-mouth disease virus (FMDV) polymerase includes residues that modulate the sensitivity to mutagenic agents. Here we have described a viable NLS mutant with an amino acid replacement that facilitates virus extinction by ribavirin. The corresponding polymerase shows increased incorporation of ribavirin triphosphate and local structural modifications that implicate the template entry channel. Specifically, comparison of the structures of ribavirin-sensitive and ribavirin-resistant FMDV polymerases has identified loop β9-α11 conformation as a determinant of sensitivity to ribavirin mutagenesis.",,"['de la Higuera, Ignacio', 'Ferrer-Orta, Cristina', 'Moreno, Elena', 'de Ávila, Ana Isabel', 'Soria, María Eugenia', 'Singh, Kamalendra', 'Caridi, Flavia', 'Sobrino, Francisco', 'Sarafianos, Stefan G.', 'Perales, Celia', 'Verdaguer, Nuria', 'Domingo, Esteban']",,,,
,PMC,microRNA-222 Attenuates Mitochondrial Dysfunction During Transmissible Gastroenteritis Virus Infection,http://dx.doi.org/10.1074/mcp.RA118.000808,PMC6317483,,,"Transmissible gastroenteritis virus (TGEV) is a member of Coronaviridae family. Our previous research showed that TGEV infection could induce mitochondrial dysfunction and upregulate miR-222 level. Therefore, we presumed that miR-222 might be implicated in regulating mitochondrial dysfunction induced by TGEV infection. To verify the hypothesis, the effect of miR-222 on mitochondrial dysfunction was tested and we showed that miR-222 attenuated TGEV-induced mitochondrial dysfunction. To investigate the underlying molecular mechanism of miR-222 in TGEV-induced mitochondrial dysfunction, a quantitative proteomic analysis of PK-15 cells that were transfected with miR-222 mimics and infected with TGEV was performed. In total, 4151 proteins were quantified and 100 differentially expressed proteins were obtained (57 upregulated, 43 downregulated), among which thrombospondin-1 (THBS1) and cluster of differentiation 47 (CD47) were downregulated. THBS1 was identified as the target of miR-222. Knockdown of THBS1 and CD47 decreased mitochondrial Ca(2+) level and increased mitochondrial membrane potential (MMP) level. Reversely, overexpression of THBS1 and CD47 elevated mitochondrial Ca(2+) level and reduced mitochondrial membrane potential (MMP) level. Together, our data establish a significant role of miR-222 in regulating mitochondrial dysfunction in response to TGEV infection.",,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Tan, Zhanhang', 'Ma, Xuelian', 'Guo, Jianxiong', 'Zhang, Zhichao', 'Du, Qian', 'Huang, Yong', 'Tong, Dewen']",,,,
,PMC,Spatiotemporal Patterns and Diffusion of the 1918 Influenza Pandemic in British India,http://dx.doi.org/10.1093/aje/kwy209,PMC6269240,,,"The factors that drive spatial heterogeneity and diffusion of pandemic influenza remain debated. We characterized the spatiotemporal mortality patterns of the 1918 influenza pandemic in British India and studied the role of demographic factors, environmental variables, and mobility processes on the observed patterns of spread. Fever-related and all-cause excess mortality data across 206 districts in India from January 1916 to December 1920 were analyzed while controlling for variation in seasonality particular to India. Aspects of the 1918 autumn wave in India matched signature features of influenza pandemics, with high disease burden among young adults, (moderate) spatial heterogeneity in burden, and highly synchronized outbreaks across the country deviating from annual seasonality. Importantly, we found population density and rainfall explained the spatial variation in excess mortality, and long-distance travel via railroad was predictive of the observed spatial diffusion of disease. A spatiotemporal analysis of mortality patterns during the 1918 influenza pandemic in India was integrated in this study with data on underlying factors and processes to reveal transmission mechanisms in a large, intensely connected setting with significant climatic variability. The characterization of such heterogeneity during historical pandemics is crucial to prepare for future pandemics.",,"['Reyes, Olivia', 'Lee, Elizabeth C', 'Sah, Pratha', 'Viboud, Cécile', 'Chandra, Siddharth', 'Bansal, Shweta']",,,,
,PMC,Diagnostic Performance of Multiplex Nucleic Acid Testing of Bronchoalveolar Lavage and Bronchial Wash Specimens for Respiratory Viral Pathogens,http://dx.doi.org/10.1128/JCM.00973-18,PMC6156318,,,"There is limited knowledge on the yield of performing multiplex nucleic acid testing (NAT) on multiple lower respiratory tract specimens from a single patient with a single instance of infection. We evaluated the performance characteristics of multiplex NAT assays performed concurrently on bronchoalveolar lavage (BAL) and bronchial wash (BW) specimens to detect respiratory pathogens. A retrospective study of admitted patients from March 2013 through December 2016 was performed. Individual performance characteristics of BAL and BW specimens were compared to positive results from either set of specimens. Only contemporaneous BAL and BW specimens (received by the laboratory within 4 h of each other) were included. The final cohort included 170 patients, with 184 contemporaneous BAL and BW specimens submitted for multiplex NAT (median age, 58 years; 62% male). Of the patients with positive NAT results, 38 of 40 BW specimens tested positive (overall percent agreement with combined testing, 98.9%; 95% confidence interval [CI], 95.5 to 98.9%), and 34 of 40 BAL specimens tested positive (overall percent agreement with combined testing, 96.7%; 95% CI, 93.0 to 96.7%). Assays performed on BW specimens identified 4 additional specimens and had a higher positive percent agreement (95.0%) with combined testing results compared to those performed on BAL specimens (85.0%). There was exact concordance in 174 specimens (94.6%; negative and positive for respiratory pathogens, 144 and 34 specimens, respectively). We observed high concordance (95%) between multiplex NAT results from contemporaneous BAL and BW specimens. Performance characteristics of BW specimen testing were equivalent to those of BAL specimen testing. The benefit of performing additional testing should be carefully considered against the potential complications and health care costs.",,"['Munigala, Satish', 'Burnham, Carey-Ann D.', 'Anderson, Neil W.', 'Liang, Stephen Y.', 'Lawrence, Steven J.', 'Warren, David K.']",,,,
,PMC,Lymphocytes are a major source of circulating soluble dipeptidyl peptidase 4,http://dx.doi.org/10.1111/cei.13163,PMC6194339,,,"Dipeptidyl peptidase 4 (DPP4, CD26) is a serine protease that is expressed constitutively by many haematopoietic and non‐haematopoietic tissues. It exists as a membrane‐associated protein, as well as in an active, soluble form (herein called sDPP4), present at high concentrations in bodily fluids. Despite the proposed use of sDPP4 as a biomarker for multiple diseases, its cellular sources are not well defined. Here, we report that individuals with congenital lymphocyte immunodeficiency had markedly lower serum concentrations of sDPP4, which were restored upon successful treatment and restoration of lymphocyte haematopoiesis. Using irradiated lymphopenic mice and wild‐type to Dpp4(–/–) reciprocal bone marrow chimeric animals, we found that haematopoietic cells were a major source of circulating sDPP4. Furthermore, activation of human and mouse T lymphocytes resulted in increased sDPP4, providing a mechanistic link between immune system activation and sDPP4 concentration. Finally, we observed that acute viral infection induced a transient increase in sDPP4, which correlated with the expansion of antigen‐specific CD8(+ )T cell responses. Our study demonstrates that sDPP4 concentrations are determined by the frequency and activation state of lymphocyte populations. Insights from these studies will support the use of sDPP4 concentration as a biomarker for inflammatory and infectious diseases.",,"['Casrouge, A.', 'Sauer, A.V.', 'Barreira da Silva, R.', 'Tejera‐Alhambra, M.', 'Sánchez‐Ramón, S.', 'ICAReB,', 'Cancrini, C.', 'Ingersoll, M.A.', 'Aiuti, A.', 'Albert, M.L.']",,,,
,PMC,Functional and structural characterization of the chikungunya virus translational recoding signals,http://dx.doi.org/10.1074/jbc.RA118.005606,PMC6231143,,,"Climate change and human globalization have spurred the rapid spread of mosquito-borne diseases to naïve populations. One such emerging virus of public health concern is chikungunya virus (CHIKV), a member of the Togaviridae family, genus Alphavirus. CHIKV pathogenesis is predominately characterized by acute febrile symptoms and severe arthralgia, which can persist in the host long after viral clearance. CHIKV has also been implicated in cases of acute encephalomyelitis, and its vertical transmission has been reported. Currently, no FDA-approved treatments exist for this virus. Recoding elements help expand the coding capacity in many viruses and therefore represent potential therapeutic targets in antiviral treatments. Here, we report the molecular and structural characterization of two CHIKV translational recoding signals: a termination codon read-through (TCR) element located between the nonstructural protein 3 and 4 genes and a programmed −1 ribosomal frameshift (−1 PRF) signal located toward the 3′ end of the CHIKV 6K gene. Using Dual-Luciferase and immunoblot assays in HEK293T and U87MG mammalian cell lines, we validated and genetically characterized efficient TCR and −1 PRF. Analyses of RNA chemical modification data with selective 2′-hydroxyl acylation and primer extension (SHAPE) assays revealed that CHIKV −1 PRF is stimulated by a tightly structured, triple-stem hairpin element, consistent with previous observations in alphaviruses, and that the TCR signal is composed of a single large multibulged hairpin element. These findings illuminate the roles of RNA structure in translational recoding and provide critical information relevant for design of live-attenuated vaccines against CHIKV and related viruses.",,"['Kendra, Joseph A.', 'Advani, Vivek M.', 'Chen, Bin', 'Briggs, Joseph W.', 'Zhu, Jinyi', 'Bress, Hannah J.', 'Pathy, Sushrut M.', 'Dinman, Jonathan D.']",,,,
,PMC,Risk factors for mortality after respiratory syncytial virus lower respiratory tract infection in adults with hematologic malignancies,http://dx.doi.org/10.1111/tid.12994,PMC6329612,,,"BACKGROUND: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with high mortality in patients with hematologic malignancies (HM). We sought to determine whether allogeneic hematopoietic cell transplant (allo-HCT) recipients would be at higher risk for 60-day mortality. METHODS: We examined a retrospective cohort of adults with HM with or without HCT treated for RSV LRTI (n=154) at our institution from 1996–2013. We defined possible RSV LRTI as RSV detected only in the upper respiratory tract with new radiologic infiltrates and proven RSV LRTI as RSV detected in BAL fluid with new radiologic infiltrates. Immunodeficiency Scoring Index (ISI) and Severe Immunodeficiency (SID) criteria were calculated for HCT recipients. Multivariable logistic regression analyses were performed to identify independent risk factors associated with 60-day all-cause mortality. RESULTS: Mortality was high in HM patients (25%), but there was no difference between those without HCT, autologous or allo-HCT recipients in logistic regression models. Separate multivariate models showed that at RSV diagnosis, neutropenia (OR 8.3, 95% CI 2.8–24.2, p=0.005) and lymphopenia (OR 3.7, 95% CI 1.7–8.2, p=0.001) were associated with 60-day mortality. Proven LRTI was associated with higher 60-day mortality (neutropenia model: OR 4.7, 95% CI 1.7–13.5; lymphopenia model: OR 3.3, 95%CI 1.2–8.8), and higher ICU admission. In HCT recipients, high ISI and very severe immunodeficiency by SID criteria were associated with higher 60-day all-cause mortality. CONCLUSIONS: Mortality is similarly high among HM patients without HCT and HCT recipients. High-grade immunodeficiency and detection of RSV from BAL fluid are associated with higher 60-day mortality.",,"['Vakil, Erik', 'Sheshadri, Ajay', 'Faiz, Saadia A.', 'Shah, Dimpy P.', 'Zhu, Yayuan', 'Li, Liang', 'Kmeid, Joumana', 'Azzi, Jacques', 'Balagani, Amulya', 'Bashoura, Lara', 'Ariza-Heredia, Ella', 'Chemaly, Roy F.']",,,,
,PMC,"51. Jahrestagung der Deutschen Gesellschaft für Transfusionsmedizin und Immunhämatologie (DGTI) 19.-21. September 2018, Lübeck",http://dx.doi.org/10.1159/000492927,PMC6198779,,,,,,,,,
,PMC,A Novel β-Glucuronidase from Talaromyces pinophilus Li-93 Precisely Hydrolyzes Glycyrrhizin into Glycyrrhetinic Acid 3-O-Mono-β-d-Glucuronide,http://dx.doi.org/10.1128/AEM.00755-18,PMC6146983,,,"Glycyrrhetinic acid 3-O-mono-β-d-glucuronide (GAMG), which possesses a higher sweetness and stronger pharmacological activity than those of glycyrrhizin (GL), can be obtained by removal of the distal glucuronic acid (GlcA) from GL. In this study, we isolated a β-glucuronidase (TpGUS79A) from the filamentous fungus Talaromyces pinophilus Li-93 that can specifically and precisely convert GL to GAMG without the formation of the by-product glycyrrhetinic acid (GA) from the further hydrolysis of GAMG. First, TpGUS79A was purified and identified through matrix-assisted laser desorption ionization–tandem time of flight mass spectrometry (MALDI-TOF-TOF MS) and deglycosylation, indicating that TpGUS79A is a highly N-glycosylated monomeric protein with a molecular mass of around 85 kDa, including around 25 kDa of glycan moiety. The gene for TpGUS79A was then cloned and verified by heterologous expression in Pichia pastoris. TpGUS79A belonged to glycoside hydrolase family 79 (GH79) but shared low amino acid sequence identity (<35%) with the available GH79 GUS enzymes. TpGUS79A had strict specificity toward the glycan moiety but poor specificity toward the aglycone moiety. Interestingly, TpGUS79A recognized and hydrolyzed the distal glucuronic bond of GL but could not cleave the glucuronic bond in GAMG. TpGUS79A showed a much higher catalytic efficiency on GL (k(cat)/K(m) of 11.14 mM(−1) s(−1)) than on the artificial substrate pNP β-glucopyranosiduronic acid (k(cat)/K(m) of 0.01 mM(−1) s(−1)), which is different from the case for most GUSs. Homology modeling, substrate docking, and sequence alignment were employed to identify the key residues for substrate recognition. Finally, a fed-batch fermentation in a 150-liter fermentor was established to prepare GAMG through GL hydrolysis by T. pinophilus Li-93. Therefore, TpGUS79A is potentially a powerful biocatalyst for environmentally friendly and cost-effective production of GAMG. IMPORTANCE Compared to chemical methods, the biotransformation of glycyrrhizin (GL) into glycyrrhetinic acid 3-O-mono-β-d-glucuronide (GAMG), which has a higher sweetness and stronger pharmacological activity than those of GL, via catalysis by β-glucuronidase is an environmentally friendly approach due to the mild reaction conditions and the high yield of GAMG. However, currently available GUSs show low substrate specificity toward GL and further hydrolyze GAMG to glycyrrhetinic acid (GA) as a by-product, increasing the difficulty of subsequent separation and purification. In the present study, we succeeded in isolating a novel β-glucuronidase (named TpGUS79A) from Talaromyces pinophilus Li-93 that specifically hydrolyzes GL to GAMG without the formation of GA. TpGUS79A also shows higher activity on GL than those of the previously characterized GUSs. Moreover, the gene for TpGUS79A was cloned and its function verified by heterologous expression in P. pastoris. Therefore, TpGUS79A can serve as a powerful biocatalyst for the cost-effective production of GAMG through GL transformation.",,"['Xu, Yinghua', 'Feng, Xudong', 'Jia, Jintong', 'Chen, Xinyi', 'Jiang, Tian', 'Rasool, Aamir', 'Lv, Bo', 'Qu, Liangti', 'Li, Chun']",,,,
,PMC,Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children,http://dx.doi.org/10.1093/cid/ciy802,PMC6784263,,,"BACKGROUND: Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a highly sensitive metagenomic next-generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children. METHODS: We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children’s hospitals from 2014–2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the National Center for Biotechnology Information nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort. RESULTS: We identified a rich cross-domain pulmonary microbiome that contained bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median, 0.61; interquartile range [IQR], 0.33–0.72 vs median, 0.96; IQR, 0.94–0.96; P < .001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (P < .001). CONCLUSIONS: An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease.",,"['Zinter, Matt S', 'Dvorak, Christopher C', 'Mayday, Madeline Y', 'Iwanaga, Kensho', 'Ly, Ngoc P', 'McGarry, Meghan E', 'Church, Gwynne D', 'Faricy, Lauren E', 'Rowan, Courtney M', 'Hume, Janet R', 'Steiner, Marie E', 'Crawford, Emily D', 'Langelier, Charles', 'Kalantar, Katrina', 'Chow, Eric D', 'Miller, Steve', 'Shimano, Kristen', 'Melton, Alexis', 'Yanik, Gregory A', 'Sapru, Anil', 'DeRisi, Joseph L']",,,,
,PMC,Strategic decision making about travel during disease outbreaks: a game theoretical approach,http://dx.doi.org/10.1098/rsif.2018.0515,PMC6170783,,,"Visitors can play an important role in the spread of infections. Here, we incorporate an epidemic model into a game theoretical framework to investigate the effects of travel strategies on infection control. Potential visitors must decide whether to travel to a destination that is at risk of infectious disease outbreaks. We compare the individually optimal (Nash equilibrium) strategy to the group optimal strategy that maximizes the overall population utility. Economic epidemiological models often find that individual and group optimal strategies are very different. By contrast, we find perfect agreement between individual and group optimal strategies across a wide parameter regime. For more limited regimes where disagreement does occur, the disagreement is (i) generally very extreme; (ii) highly sensitive to small changes in infection transmissibility and visitor costs/benefits; and (iii) can manifest either in a higher travel volume for individual optimal than group optimal strategies, or vice versa. The simulations show qualitative agreement with the 2003 severe acute respiratory syndrome (SARS) outbreak in Beijing, China. We conclude that a conflict between individual and group optimal visitor travel strategies during outbreaks may not generally be a problem, although extreme differences could emerge suddenly under certain changes in economic and epidemiological conditions.",,"['Zhao, Shi', 'Bauch, Chris T.', 'He, Daihai']",,,,
,PMC,Middle East Respiratory Syndrome Coronavirus Spike Protein Is Not Activated Directly by Cellular Furin during Viral Entry into Target Cells,http://dx.doi.org/10.1128/JVI.00683-18,PMC6146822,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes host cellular proteases to enter cells. A previous report shows that furin, which is distributed mainly in the Golgi apparatus and cycled to the cell surface and endosomes, proteolytically activates the MERS-CoV spike (S) protein following receptor binding to mediate fusion between the viral and cellular membranes. In this study, we reexamined furin usage by MERS-CoV using a real-time PCR-based virus cell entry assay after inhibition of cellular proteases. We found that the furin inhibitor dec-RVKR-CMK blocked entry of MERS-CoV harboring an S protein lacking furin cleavage sites; it even blocked entry into furin-deficient LoVo cells. In addition, dec-RVKR-CMK inhibited not only the enzymatic activity of furin but also those of cathepsin L, cathepsin B, trypsin, papain, and TMPRSS2. Furthermore, a virus cell entry assay and a cell-cell fusion assay provided no evidence that the S protein was activated by exogenous furin. Therefore, we conclude that furin does not play a role in entry of MERS-CoV into cells and that the inhibitory effect of dec-RVKR-CMK is specific for TMPRSS2 and cathepsin L rather than furin. IMPORTANCE Previous studies using the furin inhibitor dec-RVKR-CMK suggest that MERS-CoV utilizes a cellular protease, furin, to activate viral glycoproteins during cell entry. However, we found that dec-RVKR-CMK inhibits not only furin but also other proteases. Furthermore, we found no evidence that MERS-CoV uses furin. These findings suggest that previous studies in the virology field based on dec-RVKR-CMK should be reexamined carefully. Here we describe appropriate experiments that can be used to assess the effect of protease inhibitors on virus cell entry.",,"['Matsuyama, Shutoku', 'Shirato, Kazuya', 'Kawase, Miyuki', 'Terada, Yutaka', 'Kawachi, Kengo', 'Fukushi, Shuetsu', 'Kamitani, Wataru']",,,,
,PMC,The effect of chemical clarification of oral fluids on porcine epidemic diarrhea virus antibody responses,http://dx.doi.org/10.1177/1040638718798672,PMC6505836,,,"Routine testing of breeding herd oral fluid (OF) samples for porcine epidemic diarrhea virus (PEDV) IgG and/or IgA is used to track levels of PEDV immunity over time. However, OFs contain particles of feed, feces, and inorganic material that detract from the quality of the sample. We clarified swine OF samples using lyophilized chitosan-based formulas (A–C) tested by PEDV IgG and IgA ELISAs. To evaluate both the immediate and residual effects of treatment on antibody detection, samples were tested immediately post-treatment, then stored at 4°C and retested at 2, 4, and 6 days post-treatment (DPT). Formulations were shown to effectively clarify samples. Statistical analysis comparing treated to untreated OF samples at 0 DPT found that neither chitosan nor Tween 20 affected the OF ELISA IgA and IgG sample-to-positive (S/P) ratio results (p > 0.05). Furthermore, pairwise comparisons of 0 DPT to 2, 4, and 6 DPT results detected no significant differences (p > 0.05) in IgA and IgG S/P ratios (i.e., treated OF samples were stable over time). Therefore, chitosan efficiently clarified OF specimens without affecting the results of the PEDV IgG and IgA antibody ELISAs.",,"['Poonsuk, Korakrit', 'Giménez-Lirola, Luis G.', 'Magtoto, Ronaldo L.', 'Ji, Ju', 'Baum, David H.', 'Rademacher, Christopher J.', 'Brown, Justin T.', 'Zhang, Jianqiang', 'Wang, Chong', 'Main, Rodger G.', 'Zimmerman, Jeffrey J.']",,,,
,PMC,Scaling behavior of ionic transport in membrane nanochannels,http://dx.doi.org/10.1021/acs.nanolett.8b03235,PMC6242701,,,"Ionic conductance in membrane channels exhibits a power law dependence on electrolyte concentration (G ~ c(α)). The many scaling exponents α reported in the literature usually require detailed interpretations concerning each particular system under study. Here, we critically evaluate the predictive power of scaling exponents by analyzing conductance measurements in four biological channels with contrasting architectures. We show that scaling behavior depends on several interconnected effects whose contributions change with concentration so that the use of oversimplified models missing critical factors could be misleading. In fact, the presence of interfacial effects could give rise to an apparent universal scaling that hides the channel distinctive features. We complement our study with 3D structure-based Poisson-Nernst-Planck (PNP) calculations giving results in line with experiments and validating scaling arguments. Our findings not only provide a unified framework for the study of ion transport in confined geometries but also highlight that scaling arguments are powerful and simple tools to offer a comprehensive perspective of complex systems, especially those where the actual structure is unknown.",,"['Queralt-Martín, María', 'López, M. Lidón', 'Aguilella-Arzo, Marcel', 'Aguilella, Vicente M.', 'Alcaraz, Antonio']",,,,
,PMC,Characterizing replication kinetics and plaque production of type I feline infectious peritonitis virus in three feline cell lines,http://dx.doi.org/10.1016/j.virol.2018.08.022,PMC6483087,,,"Investigating type I feline coronaviruses (FCoVs) in tissue culture is critical for understanding the basic virology, pathogenesis, and virus-host interactome of these important veterinary pathogens. This has been a perennial challenge as type I FCoV strains do not easily adapt to cell culture. Here we characterize replication kinetics and plaque formation of a model type I strain FIPV Black in Fcwf-4 cells established at Cornell University (Fcwf-4 CU). We determined that maximum virus titers (>10(7) pfu/mL) were recoverable from infected Fcwf-4 CU cell-free supernatant at 20 hours post-infection. Type I FIPV Black and both biotypes of type II FCoV formed uniform and enumerable plaques on Fcwf-4 CU cells. Therefore, these cells were employable in a standardized plaque assay. Finally, we determined that the Fcwf-4 CU cells were morphologically distinct from feline bone marrow-derived macrophages and were less sensitive to exogenous type I interferon than were Fcwf-4 cells purchased from ATCC.",,"['O’Brien, Amornrat', 'Mettelman, Robert C.', 'Volk, Aaron', 'André, Nicole M.', 'Whittaker, Gary R.', 'Baker, Susan C.']",,,,
,PMC,Promoting Remyelination Through Cell Transplantation Therapies in a Model of Viral-Induced Neurodegenerative Disease,http://dx.doi.org/10.1002/dvdy.24658,PMC6420815,,,"Multiple sclerosis (MS) is a central nervous system (CNS) disease characterized by chronic neuroinflammation, demyelination, and axonal damage. Infiltration of activated lymphocytes and myeloid cells are thought to be primarily responsible for white matter damage and axonopathy. Several United States Food and Drug Administration-approved therapies exist that impede activated lymphocytes from entering the CNS thereby limiting new lesion formation in patients with relapse-remitting forms of MS. However, a significant challenge within the field of MS research is to develop effective and sustained therapies that allow for axonal protection and remyelination. In recent years, there has been increasing evidence that some kinds of stem cells and their derivatives seem to be able to mute neuroinflammation as well as promote remyelination and axonal integrity. Intracranial infection of mice with the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in immune-mediated demyelination and axonopathy, making this an excellent model to interrogate the therapeutic potential of stem cell derivatives in evoking remyelination. This review provides a succinct overview of our recent findings using intraspinal injection of mouse CNS neural progenitor cells and human neural precursors into JHMV-infected mice. JHMV-infected mice receiving these cells display extensive remyelination associated with axonal sparing. In addition, we discuss possible mechanisms associated with sustained clinical recovery.",,"['Mangale, Vrushali', 'McIntyre, Laura L.', 'Walsh, Craig M.', 'Loring, Jeanne F.', 'Lane, Thomas E.']",,,,
,PMC,Infection Prevention for The Emergency Department: Out of Reach or Standard of Care?,http://dx.doi.org/10.1016/j.emc.2018.06.013,PMC6203442,,,,,"['Liang, Stephen Y.', 'Riethman, Madison', 'Fox, Josephine']",,,,
,PMC,Poxviral promoters for improving the immunogenicity of MVA delivered vaccines,http://dx.doi.org/10.1080/21645515.2018.1513439,PMC6363155,,,"Modified vaccinia virus Ankara (MVA) is a replication-deficient poxvirus, attenuated in chick embryo fibroblast primary cells. It has been utilised as a viral vector to develop many vaccines against cancer and infectious diseases such as malaria, HIV/AIDS, influenza, and tuberculosis, MERS-CoV, and Ebola virus infection. There is accumulating data from many preclinical and clinical studies that highlights the excellent safety and immunogenicity of MVA. However, due to the complex nature of many pathogens and their pathogenicity, MVA vectored vaccine candidates need to be optimised to improve their immunogenicity. One of the main approaches to improve MVA immunogenicity focuses on optimising poxviral promoters that drive recombinant vaccine antigens, encoded within recombinant MVA vector genome. A number of promoters were described or optimised to improve the development of MVA based vaccines such as p7.5, pF11, and mH5 promoters. This review focuses on poxviral promoters, their optimisation, genetic stability, and clinical use.",,"Alharbi, Naif Khalaf",,,,
,PMC,A Recap of RNA Recapping,http://dx.doi.org/10.1002/wrna.1504,PMC6294674,,,"The N7-methylguanosine cap is a hallmark of the 5′ end of eukaryotic mRNAs and is required for gene expression. Loss of the cap was believed to lead irreversibly to decay. However, nearly a decade ago it was discovered that mammalian cells contain enzymes in the cytoplasm that are capable of restoring caps onto uncapped RNAs. In this review, we summarize recent advances in our understanding of cytoplasmic RNA recapping and discuss the biochemistry of this process and its impact on regulating and diversifying the transcriptome. Although most studies focus on mammalian RNA recapping, we also highlight new observations for recapping in disparate eukaryotic organisms, with the trypanosome recapping system appearing to be a fascinating example of convergent evolution. We conclude with emerging insights into the biological significance of RNA recapping and prospects for the future of this evolving area of study.",,"['Trotman, Jackson B.', 'Schoenberg, *Daniel R.']",,,,
,PMC,Many Canadian health facilities unprepared for disasters,http://dx.doi.org/10.1503/cmaj.109-5651,PMC6148639,,,,,"Vogel, Lauren",,,,
,PMC,Reflections from a provider of medical assistance in dying,,PMC6135143,,,,,"Reid, Tony",,,,
,PMC,Respiratory viruses in returning Hajj & Umrah pilgrims with acute respiratory illness in 2014-2015,http://dx.doi.org/10.4103/ijmr.IJMR_890_17,PMC6251276,30425224,CC BY-NC-SA,"BACKGROUND & OBJECTIVES: Respiratory tract infections are common among Hajj and Umrah pilgrims which pose a public health risk of spread of respiratory infections. Influenza has been reported from Indian Hajj and Umrah returning pilgrims, but data on other respiratory pathogens are sparse in India. Here we report the presence of common respiratory viral pathogens in returning Hajj and Umrah pilgrims suffering from acute respiratory illness (ARI) in 2014-2015. METHODS: Respiratory specimens (nasopharyngeal and throat swabs) were collected from 300 consenting pilgrims with ARI in the past one week and tested for influenza and Middle East Respiratory Syndrome coronavirus (MERS-CoV) and other respiratory viruses using in-house standardized quantitative real-time reverse-transcription polymerase chain reaction. Clinical features among the pathogen positive and negative patients were compared. The patients received symptomatic treatment and antivirals where appropriate and were followed telephonically to collect data on illness outcome. RESULTS: Ninety seven (32.3%) of the 300 participants were tested positive for any virus, most common being influenza viruses (n=33, 11%). Other respiratory viruses that were detected included human coronaviruses [n=26, 8.7%; OC43 (n=19, 6.3%) and C229E (n=7, 2.3%)], rhinovirus (n=20, 6%), adenoviruses (n=8, 2.6%), parainfluenza viruses (n=7, 2.3%), respiratory syncytial virus (n=3, 1%) and bocaviruses (n=2, 0.6%). Clinical features observed in pathogen positive and pathogen negative patients did not differ significantly. Eighteen influenza positive patients were treated with oseltamivir. INTERPRETATION & CONCLUSIONS: Pilgrims returning from mass gatherings are often afflicted with respiratory pathogens with a potential to facilitate transmission of respiratory pathogens across international borders. The study reinforces the need for better infection prevention and control measures such as vaccination, health education on cough etiquette and hand hygiene.",2018 Sep,"['Koul, Parvaiz A.', 'Mir, Hyder', 'Saha, Siddhartha', 'Chadha, Mandeep S.', 'Potdar, Varsha', 'Widdowson, Marc-Alain', 'Lal, Renu B.', 'Krishnan, Anand']",Indian J Med Res,,,
,PMC,Abstracts of Scientific Presentations,,PMC6159684,,,,,,,,,
,PMC,Facility-wide Eradication of Corynebacterium bovis by using PCR-validated Vaporized Hydrogen Peroxide,http://dx.doi.org/10.30802/AALAS-JAALAS-17-000135,PMC6159683,,,"Facility-wide Corynebacterium bovis eradication was established using vaporized hydrogen peroxide (VHP) decontamination guided by C. bovis PCR surveillance. Prior attempts limited to culling PCR-positive mice and decontaminating affected rooms were ineffective in preventing recurrence. Because research aims often require trafficking to and use of procedural cores, a 12-mo facility-wide C. bovis PCR surveillance of 2064 specimens was performed and documented that, despite the presence of few clinically hyperkeratotic mice, 35% of the murine housing and use space was contaminated by C. bovis. The airways of IVC racks and air-handling units (AHU) provided a substantive niche for C. bovis survival, comparable to the primary enclosure, with 26% of murine and 22% of airway specimens PCR-positive for C. bovis. Equipment airway VHP sterilization in a ‘flex room’ required an ‘active–closed’ setting with the IVC rack connected to the AHU set to the VHP cycle, because 12% of specimens from ‘static–open’ VHP-exposed airways remained PCR-positive for C. bovis, whereas 0% of specimens from active–closed VHP exposures were positive. VHP decontamination of the 29,931-ft(2) facility was completed in 2 mo. C. bovis PCR testing of IVC exhaust plenums for 200 d in previously C. bovis-affected rooms confirmed that none of the 259 specimens tested were PCR-positive for the organism. Monthly surveillance identified a single recurrence during June 2017 (month 9), ensuring rapid culling of C. bovis PCR-positive mice and acute VHP decontamination of equipment and rooms. Molecular persistence of C. bovis was resolved in procedural and personnel areas, and no murine or housing specimens tested C. bovis PCR-positive during study months 11 and 12. Furthermore, since the conclusion of the 12-mo study, none of the 452 additional murine, cell biologic, environmental, and monthly equipment surveillance specimens tested were C. bovis PCR-positive, documenting an 11-mo period of facility-wide C. bovis eradication to date. Study invalidation due to C. bovis can be avoided through PCR surveillance for the organism, immediate culling of PCR-positive mice, and acute VHP decontamination of affected areas.",,"['Miedel, Emily L', 'Ragland, Natalie H', 'Engelman, Robert W']",,,,
,PMC,Improving the Patency of Jugular Vein Catheters in Sprague–Dawley Rats by Using an Antiseptic Nitrocellulose Coating,http://dx.doi.org/10.30802/AALAS-JAALAS-18-000017,PMC6159680,,,"Preclinical studies in animals often require frequent blood sampling over prolonged periods. A preferred method in rats is the implantation of a polyurethane catheter into the jugular vein, with heparinized glycerol as a lock solution. However, analysis of various biologic compounds (for example, microRNA) precludes the use of heparin. We used sodium citrate as an alternative to heparin but observed more frequent loss of catheter patency. We hypothesized that this effect was due to evaporation of lock solution at the exteriorized portion of the catheter, subsequent blood infiltration into the catheter, and ultimately clot formation within the catheter. We therefore tested evaporation and its variables in vitro by using 5 common catheter materials. We used the migration of dye into vertically anchored catheters as a measure of lock displacement due to evaporation. Exposure to dry room-temperature air was sufficient to cause dye migration against gravity, whereas a humid environment and adding glycerol to the lock solution mitigated this effect, thus confirming loss of the lock solution from the catheter by evaporation. We tested 4 catheter treatments for the ability to reduce lock evaporation. Results were validated in vivo by using male Sprague–Dawley rats (n = 12) implanted with polyurethane jugular vein catheters and randomized to receive a nitrocellulose-based coating on the exteriorized portion of the catheter. Coating the catheters significantly improved patency, as indicated by a Kaplan–Meier log-rank hazard ratio greater than 5 in untreated catheters. We here demonstrate that a simple nitrocellulose coating reduces evaporation from and thus prolongs the patency of polyurethane catheters in rats.",,"['Luca, Thomas De', 'Szilágyi, Keely L', 'Hargreaves, Katherine A', 'Collins, Kimberly S', 'Benson, Eric A']",,,,
,PMC,Effects of 3 Rodent Beddings on Biochemical Measures in Rats and Mice,http://dx.doi.org/10.30802/AALAS-JAALAS-18-000023,PMC6159672,,,"Components of bedding might interact with experimental treatments and affect the outcome of various experiments. Here we studied the biochemical effects of 3 rodent bedding materials that are commonly used in Egypt. Male and female rats and mice were assigned randomly into 4 single-sex and single-species groups (10 animals per group). Three types of bedding—rice straw, wheat straw, and pine wood shavings—were evaluated. After 4 wk, animals were euthanized, and biochemical parameters were measured. In male and female rats given wood shavings, serum ALT activity and malondialdehyde concentration increased whereas catalase activity decreased compared with levels in the wheat straw group. In contrast, ALT activity and malondialdehyde concentrations decreased but CAT activity increased in rats housed on rice straw compared with wheat straw. Serum AST and ALT activities increased in male and female mice exposed to rice straw, whereas the malondialdehyde concentration increased and catalase decreased in the wood shavings group relative to the wheat straw group. In mice exposed to wheat straw, AST and ALT activities and malondialdehyde concentrations decreased and CAT activity increased compared with the other groups. Because our results showed that exposure to wood shavings affects some biochemical parameters of rats and mice, we do not recommend its use as laboratory animal bedding. We consider that, of the materials tested, rice straw bedding is the best bedding material for rats, whereas wheat straw is best for mice.",,"['Mohamed, Ayman S', 'Fahmy, Sohair R', 'Soliman, Amel M', 'Gaafar, Khadiga M']",,,,
,PMC,Ebola Virus VP40 Modulates Cell Cycle and Biogenesis of Extracellular Vesicles,http://dx.doi.org/10.1093/infdis/jiy472,PMC6249571,,,"BACKGROUND: Ebola virus (EBOV) mainly targets myeloid cells; however, extensive death of T cells is often observed in lethal infections. We have previously shown that EBOV VP40 in exosomes causes recipient immune cell death. METHODS: Using VP40-producing clones, we analyzed donor cell cycle, extracellular vesicle (EV) biogenesis, and recipient immune cell death. Transcription of cyclin D1 and nuclear localization of VP40 were examined via kinase and chromatin immunoprecipitation assays. Extracellular vesicle contents were characterized by mass spectrometry, cytokine array, and western blot. Biosafety level-4 facilities were used for wild-type Ebola virus infection studies. RESULTS: VP40 EVs induced apoptosis in recipient T cells and monocytes. VP40 clones were accelerated in growth due to cyclin D1 upregulation, and nuclear VP40 was found bound to the cyclin D1 promoter. Accelerated cell cycling was related to EV biogenesis, resulting in fewer but larger EVs. VP40 EV contents were enriched in ribonucleic acid-binding proteins and cytokines (interleukin-15, transforming growth factor-β1, and interferon-γ). Finally, EBOV-infected cell and animal EVs contained VP40, nucleoprotein, and glycoprotein. CONCLUSIONS: Nuclear VP40 upregulates cyclin D1 levels, resulting in dysregulated cell cycle and EV biogenesis. Packaging of cytokines and EBOV proteins into EVs from infected cells may be responsible for the decimation of immune cells during EBOV pathogenesis.",,"['Pleet, Michelle L', 'Erickson, James', 'DeMarino, Catherine', 'Barclay, Robert A', 'Cowen, Maria', 'Lepene, Benjamin', 'Liang, Janie', 'Kuhn, Jens H', 'Prugar, Laura', 'Stonier, Spencer W', 'Dye, John M', 'Zhou, Weidong', 'Liotta, Lance A', 'Aman, M Javad', 'Kashanchi, Fatah']",,,,
,PMC,The 135 Gene of Goatpox Virus Encodes an Inhibitor of NF-κB and Apoptosis and May Serve as an Improved Insertion Site To Generate Vectored Live Vaccine,http://dx.doi.org/10.1128/JVI.00190-18,PMC6146686,,,"Goatpox virus (GTPV) is an important member of the Capripoxvirus genus of the Poxviridae. Capripoxviruses have large and complex DNA genomes encoding many unknown proteins that may contribute to virulence. We identified that the 135 open reading frame of GTPV is an early gene that encodes an ∼18-kDa protein that is nonessential for viral replication in cells. This protein functioned as an inhibitor of NF-κB activation and apoptosis and is similar to the N1L protein of vaccinia virus. In the natural host, sheep, deletion of the 135 gene from the GTPV live vaccine strain AV41 resulted in less attenuation than that induced by deletion of the tk gene, a well-defined nonessential gene in the poxvirus genome. Using the 135 gene as the insertion site, a recombinant AV41 strain expressing hemagglutinin of peste des petits ruminants virus (PPRV) was generated and elicited stronger neutralization antibody responses than those obtained using the traditional tk gene as the insertion site. These results suggest that the 135 gene of GTPV encodes an immunomodulatory protein to suppress host innate immunity and may serve as an optimized insertion site to generate capripoxvirus-vectored live dual vaccines. IMPORTANCE Capripoxviruses are etiological agents of important diseases in sheep, goats, and cattle. There are rare reports about viral protein function related to capripoxviruses. In the present study, we found that the 135 protein of GTPV plays an important role in inhibition of innate immunity and apoptosis in host cells. Use of the 135 gene as the insertion site to generate a vectored vaccine resulted in stronger adaptive immune responses than those obtained using the tk locus as the insertion site. As capripoxviruses are promising virus-vectored vaccines against many important diseases in small ruminants and cattle, the 135 gene may serve as an improved insertion site to generate recombinant capripoxvirus-vectored live dual vaccines.",,"['Zhang, Minmin', 'Sun, Yirui', 'Chen, Weiye', 'Bu, Zhigao']",,,,
,PMC,Gallid Herpesvirus 1 Initiates Apoptosis in Uninfected Cells through Paracrine Repression of p53,http://dx.doi.org/10.1128/JVI.00529-18,PMC6146683,,,"Apoptosis is a common innate defense mechanism of host cells against viral infection and is therefore suppressed by many viruses, including herpes simplex virus (HSV), via various strategies. A recent in vivo study reported the apoptosis of remote uninfected cells during Gallid herpesvirus 1 (GaHV-1) infection, yet little is known about this previously unknown aspect of herpesvirus-host interactions. The aim of the present study was to investigate the apoptosis of uninfected host cells during GaHV-1 infection. The present study used in vitro and in ovo models, which avoided potential interference by host antiviral immunity, and demonstrated that this GaHV-1–host interaction is independent of host immune responses and important for both the pathological effect of viral infection and early viral dissemination from the primary infection site to distant tissues. Further, we revealed that GaHV-1 infection triggers this process in a paracrine-regulated manner. Using genome-wide transcriptome analyses in combination with a set of functional studies, we found that this paracrine-regulated effect requires the repression of p53 activity in uninfected cells. In contrast, the activation of p53 not only prevented the apoptosis of remote uninfected cells and subsequent pathological damage induced by GaHV-1 infection but also delayed viral dissemination significantly. Moreover, p53 activation repressed viral replication both in vitro and in ovo, suggesting that dual cell-intrinsic mechanisms underlie the suppression of GaHV-1 infection by p53 activation. This study uncovers the mechanism underlying the herpesvirus-triggered apoptosis of remote host cells and extends our understanding of both herpesvirus-host interactions and the roles of p53 in viral infection. IMPORTANCE It is well accepted that herpesviruses suppress the apoptosis of host cells via various strategies to ensure sustained viral replication during infection. However, a recent in vivo study reported the apoptosis of remote uninfected cells during GaHV-1 infection. The mechanism and the biological meaning of this unexpected herpesvirus-host interaction are unclear. This study uncovers the mechanisms of herpesvirus-triggered apoptosis in uninfected cells and may also contribute to a mechanistic illustration of paracrine-regulated apoptosis induced by other viruses in uninfected host cells.",,"['Li, Hai', 'Gao, Qi', 'Shao, Yuhao', 'Sun, Bangyao', 'Wang, Fengjie', 'Qiao, Yangyang', 'Wang, Nana', 'Liu, Shengwang']",,,,
,PMC,Feline Leukemia Virus (FeLV) Disease Outcomes in a Domestic Cat Breeding Colony: Relationship to Endogenous FeLV and Other Chronic Viral Infections,http://dx.doi.org/10.1128/JVI.00649-18,PMC6146681,,,"Exogenous feline leukemia virus (FeLV) is a feline gammaretrovirus that results in a variety of disease outcomes. Endogenous FeLV (enFeLV) is a replication-defective provirus found in species belonging to the Felis genus, which includes the domestic cat (Felis catus). There have been few studies examining interaction between enFeLV genotype and FeLV progression. We examined point-in-time enFeLV and FeLV viral loads, as well as occurrence of FeLV/enFeLV recombinants (FeLV-B), to determine factors relating to clinical disease in a closed breeding colony of cats during a natural infection of FeLV. Coinfections with feline foamy virus (FFV), feline gammaherpesvirus 1 (FcaGHV-1), and feline coronavirus (FCoV) were also documented and analyzed for impact on cat health and FeLV disease. Correlation analysis and structural equation modeling techniques were used to measure interactions among disease parameters. Progressive FeLV disease and FeLV-B presence were associated with higher FeLV proviral and plasma viral loads. Female cats were more likely to have progressive disease and FeLV-B. Conversely, enFeLV copy number was higher in male cats and negatively associated with progressive FeLV disease. Males were more likely to have abortive FeLV disease. FFV proviral load was found to correlate positively with higher FeLV proviral and plasma viral load, detection of FeLV-B, and FCoV status. Male cats were much more likely to be infected with FcaGHV-1 than female cats. This analysis provides insights into the interplay between endogenous and exogenous FeLV during naturally occurring disease and reveals striking variation in the infection patterns among four chronic viral infections of domestic cats. IMPORTANCE Endogenous retroviruses are harbored by many animals, and their interactions with exogenous retroviral infections have not been widely studied. Feline leukemia virus (FeLV) is a relevant model system to examine this question, as endogenous and exogenous forms of the virus exist. In this analysis of a large domestic cat breeding colony naturally infected with FeLV, we documented that enFeLV copy number was higher in males and inversely related to FeLV viral load and associated with better FeLV disease outcomes. Females had lower enFeLV copy numbers and were more likely to have progressive FeLV disease and FeLV-B subtypes. FFV viral load was correlated with FeLV progression. FFV, FcaGHV-1, and FeLV displayed markedly different patterns of infection with respect to host demographics. This investigation revealed complex coinfection outcomes and viral ecology of chronic infections in a closed population.",,"['Powers, Jordan A.', 'Chiu, Elliott S.', 'Kraberger, Simona J.', 'Roelke-Parker, Melody', 'Lowery, Isabella', 'Erbeck, Katelyn', 'Troyer, Ryan', 'Carver, Scott', 'VandeWoude, Sue']",,,,
,PMC,Crystal structure of the natural anion-conducting channelrhodopsin GtACR1,http://dx.doi.org/10.1038/s41586-018-0511-6,PMC6340299,,,"The naturally occurring channelrhodopsin variant anion channelrhodopsin-1 (ACR1), discovered in the cryptophyte algae Guillardia theta, exhibits large light-gated anion conductance and high anion selectivity when expressed in heterologous settings, properties that support its use as an optogenetic tool to inhibit neuronal firing with light. However, molecular insight into ACR1 is lacking owing to the absence of structural information underlying light-gated anion conductance. Here we present the crystal structure of G. theta ACR1 at 2.9 Å resolution. The structure reveals unusual architectural features that span the extracellular domain, retinal-binding pocket, Schiff-base region, and anion-conduction pathway. Together with electrophysiological and spectroscopic analyses, these findings reveal the fundamental molecular basis of naturally occurring light-gated anion conductance, and provide a framework for designing the next generation of optogenetic tools.",,"['Kim, Yoon Seok', 'Kato, Hideaki E.', 'Yamashita, Keitaro', 'Ito, Shota', 'inoue, Keiichi', 'Ramakrishnan, Charu', 'Fenno, Lief E.', 'Evans, Kathryn E.', 'Paggi, Joseph M.', 'Dror, Ron O.', 'Kandori, Hideki', 'Kobilka, Brian K.', 'Deisseroth, Karl']",,,,
,PMC,POMC: The Physiological Power of Hormone Processing,http://dx.doi.org/10.1152/physrev.00024.2017,PMC6170974,,,"Pro-opiomelanocortin (POMC) is the archetypal polypeptide precursor of hormones and neuropeptides. In this review, we examine the variability in the individual peptides produced in different tissues and the impact of the simultaneous presence of their precursors or fragments. We also discuss the problems inherent in accurately measuring which of the precursors and their derived peptides are present in biological samples. We address how not being able to measure all the combinations of precursors and fragments quantitatively has affected our understanding of the pathophysiology associated with POMC processing. To understand how different ratios of peptides arise, we describe the role of the pro-hormone convertases (PCs) and their tissue specificities and consider the cellular processing pathways which enable regulated secretion of different peptides that play crucial roles in integrating a range of vital physiological functions. In the pituitary, correct processing of POMC peptides is essential to maintain the hypothalamic-pituitary-adrenal axis, and this processing can be disrupted in POMC-expressing tumors. In hypothalamic neurons expressing POMC, abnormalities in processing critically impact on the regulation of appetite, energy homeostasis, and body composition. More work is needed to understand whether expression of the POMC gene in a tissue equates to release of bioactive peptides. We suggest that this comprehensive view of POMC processing, with a focus on gaining a better understanding of the combination of peptides produced and their relative bioactivity, is a necessity for all involved in studying this fascinating physiological regulatory phenomenon.",,"['Harno, Erika', 'Gali Ramamoorthy, Thanuja', 'Coll, Anthony P.', 'White, Anne']",,,,
,PMC,Serological Cross Reactivity between Zika and Dengue Viruses in Experimentally Infected Monkeys,http://dx.doi.org/10.1007/s12250-018-0048-8,PMC6178100,,,,,"['Mani, Shailendra', 'Tan, Chee Wah', 'Wang, Lin-Fa', 'Anderson, Danielle E.']",,,,
,PMC,Genome Characteristics of the Cyclophragma Undans Nucleopolyhedrovirus: A Distinct Species in Group I of Alphabaculovirus,http://dx.doi.org/10.1007/s12250-018-0047-9,PMC6178095,,,"The Cyclophragma undans nucleopolyhedrovirus (CyunNPV), a potential pest control agent, was isolated from Cyclophragma undans (Lepidoptera: Lasiocampidae), an important forest pest. In the present study, we performed detailed genome analysis of CyunNPV and compared its genome to those of other Group I alphabaculoviruses. Sequencing of the CyunNPV genome using the Roche 454 sequencing system generated 142,900 bp with a G + C content of 45%. Genome analysis predicted a total of 147 hypothetical open reading frames comprising 38 baculoviral core genes, 24 lepidopteran baculovirus conserved genes, nine Group I Alphabaculovirus conserved genes, 71 common genes, and five genes that are unique to CyunNPV. In addition, the genome contains 13 homologous repeated sequences (hrs). Phylogenetic analysis groups CyunNPV under a distinct branch within clade “a” of Group I in the genus Alphabaculovirus. Unlike other members of Group I, CyunNPV harbors only nine of the 11 genes previously determined to be specific to Group I viruses. Furthermore, the CyunNPV lacks the tyrosine phosphatase gene and the ac30 gene. The CyunNPV F-like protein contains two insertions of continuous polar amino acids, one at the conventional fusion peptide and a second insertion at the pre-transmembrane domain. The insertions are likely to affect the fusion function and suggest an evolutionary process that led to inactivation of the F-like protein. The above findings imply that CyunNPV is a distinct species under Group I Alphabaculovirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-018-0047-9) contains supplementary material, which is available to authorized users.",,"['Zhu, Zheng', 'Wang, Jun', 'Wang, Qianran', 'Yin, Feifei', 'Liu, Xiaoping', 'Hou, Dianhai', 'Zhang, Lei', 'Liu, Haizhou', 'Li, Jiang', 'Arif, Basil M.', 'Wang, Hualin', 'Deng, Fei', 'Hu, Zhihong', 'Wang, Manli']",,,,
,PMC,A forgotten vulnerable group: Canadian children visiting relatives in the developing world,http://dx.doi.org/10.1503/cmaj.70191,PMC6110654,,,,,"Zimmer, Rudy",,,,
,PMC,Genetic Control of Alphavirus Pathogenesis,http://dx.doi.org/10.1007/s00335-018-9776-1,PMC6488303,,,"Alphaviruses, members of the positive-sense, single-stranded RNA virus family Togaviridae, represent a re-emerging public health concern worldwide as mosquito vectors expand into new geographic ranges. Members of the alphavirus genus tend to induce clinical disease characterized by rash, arthralgia, and arthritis (chikungunya virus, Ross River virus, and Semliki Forest virus) or encephalomyelitis (eastern equine encephalitis virus, western equine encephalitis virus, and Venezuelan equine encephalitis virus), though some patients who recover from the initial acute illness may develop long term sequelae, regardless of the specific infecting virus. Studies examining the natural disease course in humans and experimental infection in cell culture and animal models reveal that host genetics play a major role in influencing susceptibility to infection and severity of clinical disease. Genome-wide genetic screens, including loss of function screens, microarrays, RNA-sequencing, and candidate gene studies have further elucidated the role host genetics play in the response to virus infection, with the immune response being found in particular to majorly influence the outcome. This review describes the current knowledge of the mechanisms by which host genetic factors influence alphavirus pathogenesis and discusses emerging technologies that are poised to increase our understanding of the complex interplay between viral and host genetics on disease susceptibility and clinical outcome.",,"['Baxter, Victoria K.', 'Heise, Mark T.']",,,,
,PMC,Transposable Element Dysregulation in Systemic Lupus Erythematosus and Regulation by Histone Conformation and Hsp90,http://dx.doi.org/10.1016/j.clim.2018.08.011,PMC6258342,,,"Systemic lupus erythematosus (SLE) represents an autoimmune disease in which activation of the type I interferon pathway leads to dysregulation of tolerance and the generation of autoantibodies directed against nuclear constituents. The mechanisms driving the activation of the interferon pathway in SLE have been the subject of intense investigation but are still incompletely understood. Transposable elements represent an enormous source of RNA that could potentially stimulate the cell intrinsic RNA-recognition pathway, leading to upregulation of interferons. We used RNA-seq to define transposable element families and subfamilies in three cell types in SLE and found diverse effects on transposable element expression in the three cell types and even within a given family of transposable elements. When potential mechanisms were examined, we found that Hsp90 inhibition could drive increased expression of multiple type of transposable elements. Both direct inhibition and the delivery of a heat shock itself, which redirects heat shock regulators (including Hsp90) off of basal expression promoters and onto heat shock-responsive promoters, led to increased transposable element expression. This effect was amplified by the concurrent delivery of a histone deacetylase inhibitor. We conclude that transposable elements are dysregulated in SLE and there are tissue-specific effects and locus-specific effects. The magnitude of RNAs attributable to transposable elements makes their dysregulation of critical interest in SLE where transposable element RNA complexed with proteins has been shown to drive interferon expression.",,"['Kelly, Maurer', 'Lihua, Shi', 'Zhe, Zhang', 'Li, Song', 'Yoselin, Paucar', 'Michelle, Petri', 'E, Sullivan Kathleen']",,,,
,PMC,Prevalence and Etiology of Community-acquired Pneumonia in Immunocompromised Patients,http://dx.doi.org/10.1093/cid/ciy723,PMC6481991,,,"BACKGROUND: The correct management of immunocompromised patients with pneumonia is debated. We evaluated the prevalence, risk factors, and characteristics of immunocompromised patients coming from the community with pneumonia. METHODS: We conducted a secondary analysis of an international, multicenter study enrolling adult patients coming from the community with pneumonia and hospitalized in 222 hospitals in 54 countries worldwide. Risk factors for immunocompromise included AIDS, aplastic anemia, asplenia, hematological cancer, chemotherapy, neutropenia, biological drug use, lung transplantation, chronic steroid use, and solid tumor. RESULTS: At least 1 risk factor for immunocompromise was recorded in 18% of the 3702 patients enrolled. The prevalences of risk factors significantly differed across continents and countries, with chronic steroid use (45%), hematological cancer (25%), and chemotherapy (22%) the most common. Among immunocompromised patients, community-acquired pneumonia (CAP) pathogens were the most frequently identified, and prevalences did not differ from those in immunocompetent patients. Risk factors for immunocompromise were independently associated with neither Pseudomonas aeruginosa nor non–community-acquired bacteria. Specific risk factors were independently associated with fungal infections (odds ratio for AIDS and hematological cancer, 15.10 and 4.65, respectively; both P = .001), mycobacterial infections (AIDS; P = .006), and viral infections other than influenza (hematological cancer, 5.49; P < .001). CONCLUSIONS: Our findings could be considered by clinicians in prescribing empiric antibiotic therapy for CAP in immunocompromised patients. Patients with AIDS and hematological cancer admitted with CAP may have higher prevalences of fungi, mycobacteria, and noninfluenza viruses.",,"['Di Pasquale, Marta Francesca', 'Sotgiu, Giovanni', 'Gramegna, Andrea', 'Radovanovic, Dejan', 'Terraneo, Silvia', 'Reyes, Luis F', 'Rupp, Jan', 'González del Castillo, Juan', 'Blasi, Francesco', 'Aliberti, Stefano', 'Restrepo, Marcos I', None]",,,,
,PMC,Genomic and epidemiological monitoring of yellow fever virus transmission potential,http://dx.doi.org/10.1126/science.aat7115,PMC6874500,,,"The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes sp. mosquitos highlights a need to monitor the risk of re-establishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial and genomic approaches to characterize YFV transmission. We show that the age- and sex-distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion towards previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real-time that will contribute to a global strategy to eliminate future YFV epidemics.",,"['Faria, N. R.', 'Kraemer, M. U. G.', 'Hill, S. C.', 'Goes de Jesus, J.', 'de Aguiar, R. S.', 'Iani, F. C. M.', 'Xavier, J.', 'Quick, J.', 'du Plessis, L.', 'Dellicour, S.', 'Thézé, J.', 'Carvalho, R. D. O.', 'Baele, G.', 'Wu, C.-H.', 'Silveira, P. P.', 'Arruda, M. B.', 'Pereira, M. A.', 'Pereira, G. C.', 'Lourenço, J.', 'Obolski, U.', 'Abade, L.', 'Vasylyeva, T. I.', 'Giovanetti, M.', 'Yi, D.', 'Weiss, D.J.', 'Wint, G. R. W.', 'Shearer, F. M.', 'Funk, S.', 'Nikolai, B.', 'Fonseca, V.', 'Adelino, T. E. R.', 'Oliveira, M. A. A.', 'Silva, M. V. F.', 'Sacchetto, L.', 'Figueiredo, P. O.', 'Rezende, I. M.', 'Mello, E. M.', 'Said, R. F. C.', 'Santos, D. A.', 'Ferraz, M. L.', 'Brito, M. G.', 'Santana, L. F.', 'Menezes, M. T.', 'Brindeiro, R. M.', 'Tanuri, A.', 'dos Santos, F. C. P.', 'Cunha, M. S.', 'Nogueira, J. S.', 'Rocco, I., M.', 'da Costa, A. C.', 'Komninakis, S. C. V.', 'Azevedo, V.', 'Chieppe, A. O.', 'Araujo, E. S. M.', 'Mendonça, M. C. L.', 'dos Santos, C. C.', 'dos Santos, C. D.', 'Mares-Guia, A. M.', 'Nogueira, R. M. R.', 'Sequeira, P. C.', 'Abreu, R. G.', 'Garcia, M. H. O.', 'Abreu, A. L.', 'Okumoto, O.', 'Kroon, E. G.', 'de Albuquerque, C. F. C.', 'Lewandowski, K.', 'Pullan, S. T.', 'Carroll, M.', 'de Oliveira, T.', 'Sabino, E. C.', 'Souza, R. P.', 'Suchard, M. A.', 'Lemey, P.', 'Trindade, G. S.', 'Drumond, B. P.', 'Filippis, A. M. B.', 'Loman, N. J.', 'Cauchemez, S.', 'Alcantara, L. C. J.', 'Pybus, O. G.']",,,,
,PMC,Phosphoserine acidic cluster motifs bind distinct basic regions on the μ subunits of clathrin adaptor protein complexes,http://dx.doi.org/10.1074/jbc.RA118.003080,PMC6177606,,,"Protein trafficking in the endosomal system involves the recognition of specific signals within the cytoplasmic domains (CDs) of transmembrane proteins by clathrin adaptors. One such signal is the phosphoserine acidic cluster (PSAC), the prototype of which is in the endoprotease furin. How PSACs are recognized by clathrin adaptors has been controversial. We reported previously that HIV-1 Vpu, which modulates cellular immunoreceptors, contains a PSAC that binds to the μ subunits of clathrin adaptor protein (AP) complexes. Here, we show that the CD of furin binds the μ subunits of AP-1 and AP-2 in a phosphorylation-dependent manner. Moreover, we identify a potential PSAC in a cytoplasmic loop of the cellular transmembrane Serinc3, an inhibitor of the infectivity of retroviruses. The two serines within the PSAC of Serinc3 are phosphorylated by casein kinase II and mediate interaction with the μ subunits in vitro. The sites of these serines vary among mammals in a manner suggesting host–pathogen conflict, yet the Serinc3 PSAC seems dispensable for anti-HIV activity and for counteraction by HIV-1 Nef. The CDs of Vpu and furin and the PSAC-containing loop of Serinc3 each bind the μ subunit of AP-2 (μ2) with similar affinities, but they appear to utilize different basic regions on μ2. The Serinc3 loop requires a region previously reported to bind the acidic plasma membrane lipid phosphatidylinositol 4,5-bisphosphate. These data suggest that the PSACs within different proteins recognize different basic regions on the μ surface, providing the potential to inhibit the activity of viral proteins without necessarily affecting cellular protein trafficking.",,"['Singh, Rajendra', 'Stoneham, Charlotte', 'Lim, Christopher', 'Jia, Xiaofei', 'Guenaga, Javier', 'Wyatt, Richard', 'Wertheim, Joel O.', 'Xiong, Yong', 'Guatelli, John']",,,,
,PMC,Otitis and meningoencephalitis associated with infectious coryza (Avibacterium paragallinarum) in commercial broiler chickens,http://dx.doi.org/10.1177/1040638718792964,PMC6505790,,,"Infectious coryza, caused by Avibacterium paragallinarum, is an acute respiratory disease of poultry that can result in substantial morbidity, mortality, and economic losses. In March 2017, the Turlock branch of the California Animal Health and Food Safety laboratory system encountered an unusual clinical and pathologic presentation of infectious coryza in 6 live, 29-d-old, commercial broiler chickens that were submitted for diagnostic investigation. Antemortem evaluation revealed severe neurologic signs, including disorientation, torticollis, and opisthotonos. Swollen head–like syndrome and sinusitis were also present. Histologically, severe sinusitis, cranial osteomyelitis, otitis media and interna, and meningoencephalitis were noted, explaining the clinical signs described. A. paragallinarum was readily isolated from the upper and lower respiratory tract, brain, and cranial bones. Infectious bronchitis virus (IBV) was also detected by PCR, and IBV was isolated in embryonated chicken eggs. Based on sequencing analysis, the IBV appeared 99% homologous to strain CA1737. A synergistic effect between A. paragallinarum and IBV, resulting in exacerbation of clinical signs and increased mortality, may have occurred in this case. A. paragallinarum should be considered among the possible causes of neurologic signs in chickens. Appropriate media should be used for bacterial isolation, and the role of additional contributing factors and/or complicating agents should be investigated in cases of infectious coryza.",,"['Crispo, Manuela', 'Sentíes-Cué, C. Gabriel', 'Cooper, George L.', 'Mountainspring, Grace', 'Corsiglia, Charles', 'Bickford, Arthur A.', 'Stoute, Simone T.']",,,,
,PMC,Human dendritic cell-specific ICAM-3-grabbing non-integrin downstream signaling alleviates renal fibrosis via Raf-1 activation in systemic candidiasis,http://dx.doi.org/10.1038/s41423-018-0161-5,PMC6460490,,,"We generated a human dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN) transgenic mouse in which renal tubular epithelial cells expressed DC-SIGN. The transgenic mice were infected with Candida albicans intravenously to study how DC-SIGN expression affected the pathogenesis of systemic candidiasis. We discovered that, while C. albicans infection induced renal fibrosis in both transgenic and littermate control mice, the transgenic mice had significantly lower levels of Acta2, Col1a2, Col3a1, and Col4a1 mRNA transcripts compared to the controls. KIM-1, an emerging biomarker for kidney injury, along with Tnf, Il6, and Tgfb1 transcripts, were lower in infected transgenic mice, and yet, the levels of Il10 remained comparable to the controls. While renal CD45(+) infiltrating cells were the source of Tnf, Il6, and Il10, LTL(+) renal proximal tubular epithelial cells were TGF-β1 producers in both infected transgenic and littermate controls. DC-SIGN-expressing tubular epithelial cells produced less TGF-β1 in response to C. albicans infection. In vivo experiments demonstrated that renal proximal tubular epithelial cell production of TGF-β1 was key to C. albicans-induced renal fibrosis and injury. Infection of transgenic mice induced a marked increase of phosphorylated Raf-1 and p38 in the kidney. However, ERK1/2 and JNK phosphorylation was more pronounced in the infected-littermate controls. Interestingly, treating the infected transgenic mice with a Raf-1 inhibitor increased the levels of the Tgfb1, Kim1, and Acta2 transcripts. These results indicate that DC-SIGN signaling, through activation of Raf-1 and p38 and suppression of JNK and ERK1/2 phosphorylation, reduces TGF-β1 production and C. albicans-induced renal fibrosis. Our study reveals for the first time the effect of DC-SIGN expression on C. albicans-induced renal fibrosis.",,"['Chen, Wen-Yu', 'Wu, Sheng-Yang', 'Lin, Ta-Chun', 'Lin, Shuei-Liong', 'Wu-Hsieh, Betty A.']",,,,
,PMC,Delineating the Cellular Mechanisms Associated with Skin Electroporation,http://dx.doi.org/10.1089/hgtb.2017.105,PMC6421993,,,"The immune responses elicited following delivery of DNA vaccines to the skin has previously been shown to be significantly enhanced by the addition of electroporation (EP) to the treatment protocol. Principally, EP increases the transfection of plasmid DNA (pDNA) into the resident skin cells. In addition to increasing the levels of in vivo transfection, the physical insult induced by EP is associated with activation of innate pathways which are believed to mediate an adjuvant effect, further enhancing DNA vaccine responses. We investigated the possible mechanisms associated with this adjuvant effect, primarily focusing on the cell death pathways associated with the skin EP procedure independent of pDNA delivery. Using the minimally invasive CELLECTRA(®)-3P intradermal electroporation device that penetrates the epidermal and dermal layers of the skin, we have investigated apoptotic and necrotic cell death in relation to the vicinity of the electrode needles and electric field generated. Employing the well-established terminal deoxynucleotidyl transferase nick-end labeling assay, we detected apoptosis beginning as early as one hour after EP and peaking at the 4 h time point. The majority of the apoptotic events were detected in the epidermal region directly adjacent to the electrode needle. Using a novel propidium iodide in vivo necrotic cell death assay, we detected necrotic events concentrated in the epidermal region adjacent to the electrode. Furthermore, we detected upregulation of calreticulin expression on skin cells after EP, thus labeling these cells for uptake by dendritic cells and macrophages. These results allow us to delineate the cell death mechanisms occurring in the skin following intradermal EP independently of pDNA delivery. We believe these events contribute to the adjuvant effect observed following electroporation at the skin treatment site.",,"['Schultheis, Katherine', 'Smith, Trevor R.F.', 'Kiosses, William B.', 'Kraynyak, Kimberly A.', 'Wong, Amelia', 'Oh, Janet', 'Broderick, Kate E.']",,,,
,PMC,"UVC LED Irradiation Effectively Inactivates Aerosolized Viruses, Bacteria, and Fungi in a Chamber-Type Air Disinfection System",http://dx.doi.org/10.1128/AEM.00944-18,PMC6102977,,,"In this study, the possibility of inactivating viral, bacterial, and fungal aerosols in a chamber-type air disinfection system by using a UVC light-emitting-diode (LED) array was investigated and inactivation rate constants of each microorganism were calculated in fitting curves of surviving populations. UVC LED array treatment effectively inactivated viral infectivity, achieving 5-log reductions within 45 mJ/cm(2) for MS2, Qβ, and ϕX174 viruses. UVC LED array effectiveness in inactivating Escherichia coli O157:H7, Salmonella enterica serovar Typhimurium, Listeria monocytogenes, and Staphylococcus aureus aerosols achieved 2.5- to 4-log reductions within 1.5 to 4.6 mJ/cm(2). Also, 4-log reductions of Aspergillus flavus and Alternaria japonica were achieved at a dosage of 23 mJ/cm(2) using UVC LED array irradiation. The highest UV susceptibility, represented by the inactivation rate constant, was calculated for bacteria, followed by fungi and viruses. UVC LED, an innovative technology, can effectively inactivate microorganisms regardless of taxonomic classification and can sufficiently substitute for conventional mercury UV lamps. IMPORTANCE The United Nations Environment Programme (UNEP) convened the Minamata Convention on Mercury in 2013 to ban mercury-containing products in order to ensure human and environmental health. It will be effectuated in 2020 to discontinue use of low-pressure mercury lamps and new UV-emitting sources have to replace this conventional technology. However, the UV germicidal irradiation (UVGI) system still uses conventional UV lamps, and no research has been conducted for air disinfection using UVC LEDs. The research reported here investigated the inactivation effect of aerosolized microorganisms, including viruses, bacteria, and fungi, with an UVC LED module. The results can be utilized as a primary database to replace conventional UV lamps with UVC LEDs, a novel type of UV emitter. Implementation of UVC LED technology is truly expected to significantly reduce the extent of global mercury contamination, and this study provides important baseline data to help ensure a healthier environment and increased health for humanity.",,"['Kim, Do-Kyun', 'Kang, Dong-Hyun']",,,,
,PMC,Viral strategies for triggering and manipulating mitophagy,http://dx.doi.org/10.1080/15548627.2018.1466014,PMC6135629,,,"Viral infection causes many physiological alterations in the host cell, and many of these alterations can affect the host mitochondrial network, including mitophagy induction. A substantial amount of literature has been generated that advances our understanding of the relationship between mitophagy and several viruses. Some viruses trigger mitophagy directly, and indirectly and control the mitophagic process via different strategies. This enables viruses to promote persistent infection and attenuate the innate immune responses. In this review, we discuss the events of virus-regulated mitophagy and the functional relevance of mitophagy in the pathogenesis of viral infection and disease. Abbreviation: ATG: autophagy related; BCL2L13: BCL2 like 13; BNIP3L/NIX: BCL2 interacting protein 3 like; CL: cardiolipin; CSFV: classical swine fever virus; CVB: coxsackievirus B; DENV: dengue virus; DNM1L: dynamin 1 like; FIS1: fission, mitochondrial 1; FUNDC1: FUN14 domain containing 1; HPIV3: human parainfluenza virus 3; HSV-1: herpes simplex virus type 1; IMM: inner mitochondrial membrane; IAV: influenza A virus; IFN: interferon; IKBKE/IKKϵ: inhibitor of nuclear factor kappa B kinase subunit epsilon; LUBAC: linear ubiquitin assembly complex; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MeV: measles virus; MAVS: mitochondrial antiviral signaling protein; MFF: mitochondria fission factor; NLRP3: NLR family pyrin domain containing 3; NDV: Newcastle disease virus; NR4A1: nuclear receptor subfamily 4 group A member 1; OMM: outer mitochondrial membrane; OPA1: OPA1, mitochondrial dynamin like GTPase; PRKN: parkin RBR E3 ubiquitin protein ligase; PINK1: PTEN induced putative kinase 1; PHB2: prohibitin 2; PRRSV: porcine reproductive and respiratory syndrome virus; PRRs: pattern-recognition receptors; RLRs: RIG-I-like receptors; ROS: reactive oxygen species; RIPK2: receptor interacting serine/threonine kinase 2; SESN2: sestrin 2; SNAP29: synaptosome associated protein 29; STX17: syntaxin 17; TGEV: transmissible gastroenteritis virus; TUFM: Tu translation elongation factor, mitochondrial; TRAF2: TNF receptor associated factor 2; TRIM6: tripartite motif containing 6; Ub: ubiquitin; ULK1: unc-51 like autophagy activating kinase 1; VZV: varicella-zoster virus",,"['Zhang, Linliang', 'Qin, Yali', 'Chen, Mingzhou']",,,,
,PMC,Limiting respiratory viral infection by targeting antiviral and immunological functions of BST-2/Tetherin: Knowledge and gaps,http://dx.doi.org/10.1002/bies.201800086,PMC6371793,,,"Recent findings regarding the cellular biology and immunology of BST-2 (also known as tetherin) indicate that its function could be exploited as a universal replication inhibitor of enveloped respiratory viruses (e.g., influenza, respiratory syncytial virus, etc.). BST-2 inhibits viral replication by preventing virus budding from the plasma membrane and by inducing an antiviral state in cells adjacent to infection via unique inflammatory signaling mechanisms. This review presents the first comprehensive summary of what is currently known about BST-2 antiviral function against respiratory viruses, how these viruses construct countermeasures to antagonize BST-2, and how BST-2 function might be targeted to develop therapies to treat respiratory virus infections. We address the current gaps in knowledge, including the need for mechanistic understanding of BST-2 antagonism by respiratory viruses, that should be bridged to achieve that goal.",,"['Berry, Kayla N.', 'Kober, Daniel L.', 'Su, Alvin', 'Brett, Tom J.']",,,,
,PMC,A screening campaign in sea urchin egg homogenate as a platform for discovering modulators of NAADP-dependent Ca(2+) signaling in human cells,http://dx.doi.org/10.1016/j.ceca.2018.08.002,PMC6286156,,,"The Ca(2+) mobilizing second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) regulates intracellular trafficking events, including translocation of certain enveloped viruses through the endolysosomal system. Targeting NAADP-evoked Ca(2+) signaling may therefore be an effective strategy for discovering novel antivirals as well as therapeutics for other disorders. To aid discovery of novel scaffolds that modulate NAADP-evoked Ca(2+) signaling in human cells, we have investigated the potential of using the sea urchin egg homogenate system for a screening campaign. Known pharmacological inhibitors of NAADP-evoked Ca(2+) release (but not cADPR- or IP(3)-evoked Ca(2+) release) in this invertebrate system strongly correlated with inhibition of MERS-pseudovirus infectivity in a human cell line. A primary screen of 1534 compounds yielded eighteen ‘hits’ exhibiting >80% inhibition of NAADP-evoked Ca(2+) release. A validation pipeline for these candidates yielded seven drugs that inhibited NAADP-evoked Ca(2+) release without depleting acidic Ca(2+) stores in a human cell line. These candidates displayed a similar penetrance of inhibition in both the sea urchin system and the human cell line, and the extent of inhibition of NAADP-evoked Ca(2+) signals correlated well with observed inhibition of infectivity of a Middle East Respiratory syndrome coronavirus (MERS-CoV) pseudovirus. These experiments support the potential of this simple, homogenate system for screening campaigns to discover modulators of NAADP, cADPR and IP(3)-dependent Ca(2+) signaling with potential therapeutic value.",,"['Gunaratne, Gihan S.', 'Johns, Malcolm E.', 'Hintz, Hallie M.', 'Walseth, Timothy F.', 'Marchant, Jonathan S.']",,,,
,PMC,Strand-Specific Dual RNA Sequencing of Bronchial Epithelial Cells Infected with Influenza A/H3N2 Viruses Reveals Splicing of Gene Segment 6 and Novel Host-Virus Interactions,http://dx.doi.org/10.1128/JVI.00518-18,PMC6096831,,,"Host-influenza virus interplay at the transcript level has been extensively characterized in epithelial cells. Yet, there are no studies that simultaneously characterize human host and influenza A virus (IAV) genomes. We infected human bronchial epithelial BEAS-2B cells with two seasonal IAV/H3N2 strains, Brisbane/10/07 and Perth/16/09 (reference strains for past vaccine seasons) and the well-characterized laboratory strain Udorn/307/72. Strand-specific RNA sequencing (RNA-seq) of the infected BEAS-2B cells allowed for simultaneous analysis of host and viral transcriptomes, in addition to pathogen genomes, to reveal changes in mRNA expression and alternative splicing (AS). In general, patterns of global and immune gene expression induced by the three IAVs were mostly shared. However, AS of host transcripts and small nuclear RNAs differed between the seasonal and laboratory strains. Analysis of viral transcriptomes showed deletions of the polymerase components (defective interfering-like RNAs) within the genome. Surprisingly, we found that the neuraminidase gene undergoes AS and that the splicing event differs between seasonal and laboratory strains. Our findings reveal novel elements of the host-virus interaction and highlight the importance of RNA-seq in identifying molecular changes at the genome level that may contribute to shaping RNA-based innate immunity. IMPORTANCE The use of massively parallel RNA sequencing (RNA-seq) has revealed insights into human and pathogen genomes and their evolution. Dual RNA-seq allows simultaneous dissection of host and pathogen genomes and strand-specific RNA-seq provides information about the polarity of the RNA. This is important in the case of negative-strand RNA viruses like influenza virus, which generate positive (complementary and mRNA) and negative-strand RNAs (genome) that differ in their potential to trigger innate immunity. Here, we characterize interactions between human bronchial epithelial cells and three influenza A/H3N2 strains using strand-specific dual RNA-seq. We focused on this subtype because of its epidemiological importance in causing significant morbidity and mortality during influenza epidemics. We report novel elements that differ between seasonal and laboratory strains highlighting the complexity of the host-virus interplay at the RNA level.",,"['Fabozzi, Giulia', 'Oler, Andrew J.', 'Liu, Poching', 'Chen, Yong', 'Mindaye, Samuel', 'Dolan, Michael A.', 'Kenney, Heather', 'Gucek, Marjan', 'Zhu, Jun', 'Rabin, Ronald L.', 'Subbarao, Kanta']",,,,
,PMC,Reduced Susceptibility to VIRIP-Based HIV-1 Entry Inhibitors Has a High Genetic Barrier and Severe Fitness Costs,http://dx.doi.org/10.1128/JVI.00733-18,PMC6096827,,,"VIRIP has been identified as natural HIV-1 inhibitor targeting the gp41 fusion peptide. An optimized analogue (VIR-576) was effective in a phase I/II clinical trial and initial studies showed that HIV-1 resistance to VIRIP-based inhibitors has a high genetic barrier. Partially resistant CXCR4 (X4)-tropic HIV-1 NL4-3 variants could be obtained, however, after more than 15 months of passaging in MT-4 cells in the presence of another derivative (VIR-353). Sequence analyses identified the accumulation of seven mutations across the HIV-1 envelope glycoprotein but outside the gp41 fusion peptide. The authors suggested that the three initial alterations conferred resistance, while subsequent changes restored viral fitness. Here, we introduced these mutations individually and in combination into X4- and CCR5 (R5)-tropic HIV-1 constructs and determined their impact on VIR-353 and VIR-576 susceptibility, viral infectivity, replication fitness, and fusogenicity. We found that essentially all seven mutations contribute to reduced susceptibility to VIRIP-based inhibitors. HIV-1 constructs containing ≥4 changes were substantially more resistant to both VIRIP-based inhibitors and the VRC34.01 antibody targeting the fusion peptide. However, they were also much less infectious and fusogenic than those harboring only the three initial alterations. Furthermore, the additional changes attenuated rather than rescued HIV-1 replication in primary human cells. Thus, the genetic barrier to HIV-1 resistance against VIRIP-based inhibitors is higher than previously suggested, and mutations reducing viral susceptibility come at a severe fitness cost that was not rescued during long-term cell culture passage. IMPORTANCE Many viral pathogens are critically dependent on fusion peptides (FPs) that are inserted into the cellular membrane for infection. Initially, it was thought that FPs cannot be targeted for therapy because they are hardly accessible. However, an optimized derivative (VIR-576) of an endogenous fragment of α1-antitrypsin, named VIRIP, targeting the gp41 FP reduced viral loads in HIV-1-infected individuals. Characterization of HIV-1 variants selected during long-term cell-culture passage in the presence of a VIRIP derivative suggested that just three mutations in the HIV-1 Env protein might be sufficient for VIRIP resistance and that four subsequent changes restored viral fitness. Here, we show that all seven mutations contribute to reduced viral susceptibility to VIRIP-based inhibitors and demonstrate that the additional changes strongly impair rather than rescue HIV-1 infectivity, fusogenicity, and replication fitness. High genetic barrier to resistance and severe fitness cost support further clinical development of this class of antiviral agents.",,"['Müller, Janis A.', 'Glöckle, Anna', 'Gawanbacht, Ali', 'Geyer, Matthias', 'Münch, Jan', 'Kirchhoff, Frank']",,,,
,PMC,CD8(+) T-Cell Response-Associated Evolution of Hepatitis B Virus Core Protein and Disease Progress,http://dx.doi.org/10.1128/JVI.02120-17,PMC6096822,,,"Under the immune pressure of cytotoxic T cells (CTLs), hepatitis B virus (HBV) evolves to accumulate mutations more likely within epitopes to evade immune detection. However, little is known about the specific patterns of the immune pressure-associated HBV mutation of T-cell epitopes and their link to disease progression. Here, we observed a correlation of the accumulated variants on HBV core protein (HBc) with the disease severity of HBV infection. Further analysis indicated that these substitutions were mostly located within CD8(+) T-cell epitopes of HBc protein, which were systematically screened and identified in an unbiased manner in our study. From individual peptide level to the human leukocyte antigen I (HLA-I)-restricted population level, we elucidated that the mutations in these well-defined HLA-I-restricted T-cell epitopes significantly decreased antiviral activity-specific CTLs and were positively associated with clinical parameters and disease progression in HBV-infected patients. The molecular pattern for viral epitope variations based on the sequencing of 105 HBV virus genomes indicated that the C-terminal portion (Pc), especially the Pc-1 and Pc-2 positions, have the highest mutation rates. Further structural analysis of HLA-A*02 complexed to diverse CD8(+) T-cell epitopes revealed that the highly variable C-terminal bulged peak of M-shaped HBc-derived epitopes are solvent exposed, and most of the CDR3βs of the T-cell receptor hover over them. These data shed light on the molecular and immunological mechanisms of T-cell immunity-associated viral evolution in hepatitis B progression, which is beneficial for designing immunotherapies and vaccines. IMPORTANCE The specific patterns of sequence polymorphisms of T-cell epitopes and the immune mechanisms of the HBV epitope mutation-linked disease progression are largely unclear. In this study, we systematically evaluated the contribution of CD8(+) T cells to the disease progress-associated evolution of HBV. By evaluation of patient T-cell responses based on the peptide repertoire, we comprehensively characterized the association of clinical parameters in chronic hepatitis B with the antiviral T-cell response-associated mutations of the viruses from the single-epitope level to the overall HLA-I-restricted peptide levels. Furthermore, we investigated the molecular basis of the HLA-A2-restricted peptide immune escape and found that the solvent-exposed C-terminal portion of the epitopes is highly variable under CDR3β recognition. Our work may provide a comprehensive evaluation of viral mutations impacted by the host CTL response in HBV disease progression in the context of the full repertoire of HBc-derived epitopes.",,"['Zhang, Yu', 'Wu, Yan', 'Deng, Mengmeng', 'Xu, Dongping', 'Li, Xiaodong', 'Xu, Zhihui', 'Hu, Jun', 'Zhang, Han', 'Liu, Kefang', 'Zhao, Yingze', 'Gao, Feng', 'Bi, Shengli', 'Gao, George F.', 'Zhao, Jingmin', 'Liu, William J.', 'Meng, Songdong']",,,,
,PMC,Articles of Significant Interest in This Issue,http://dx.doi.org/10.1128/JVI.01194-18,PMC6096816,,,,,,,,,
,PMC,Dimerization of Coronavirus nsp9 with Diverse Modes Enhances Its Nucleic Acid Binding Affinity,http://dx.doi.org/10.1128/JVI.00692-18,PMC6096807,,,"Coronaviruses pose serious health threats to humans and other animals. Understanding the mechanisms of their replication has important implications for global health and economic stability. Nonstructural protein 9 (nsp9) is an essential RNA binding protein for coronavirus replication. However, the mechanisms of the dimerization and nucleic acid binding of nsp9 remain elusive. Here, we report four crystal structures, including wild-type porcine delta coronavirus (PDCoV) nsp9, PDCoV nsp9-ΔN7 (N-terminal 7 amino acids deleted), wild-type porcine epidemic diarrhea virus (PEDV) nsp9, and PEDV nsp9-C59A mutant. These structures reveal the diverse dimerization forms of coronavirus nsp9. We first found that the N-finger of nsp9 from PDCoV plays a critical role in dimerization. Meanwhile, PEDV nsp9 is distinguished by the presence of a disulfide bond in the dimer interface. Interestingly, size exclusion chromatography and analytical ultracentrifugation analyses indicate that the PDCoV nsp9-ΔN7 and PEDV nsp9-C59A mutants are monomeric in solution. In addition, electrophoretic mobility shift assays and microscale thermophoresis analysis indicate that the monomeric forms of PDCoV nsp9 and PEDV nsp9 still have nucleic acid binding affinity, although it is lower than that of the wild type. Our results show that the diverse dimerization forms of coronavirus nsp9 proteins enhance their nucleic acid binding affinity. IMPORTANCE Coronaviruses cause widespread respiratory, gastrointestinal, and central nervous system diseases in humans and other animals, threatening human health and causing economic loss. Coronavirus nsp9, a member of the replication complex, is an important RNA binding subunit in the RNA-synthesizing machinery of all coronaviruses. However, the mechanisms of the dimerization and nucleic acid binding of nsp9 remain elusive. In this study we determined the nsp9 crystal structures of PDCoV and PEDV. We first found that the N-finger of nsp9 from PDCoV plays a critical role in dimerization. Meanwhile, PEDV nsp9 is distinguished by the presence of a disulfide bond in the dimer interface. This study provides a structural and functional basis for understanding the mechanism of dimerization and shows that the diverse dimerization modes of coronavirus nsp9 proteins enhance their nucleic acid binding affinity. Importantly, these findings may provide a new insight for antiviral drug development.",,"['Zeng, Zhe', 'Deng, Feng', 'Shi, Ke', 'Ye, Gang', 'Wang, Gang', 'Fang, Liurong', 'Xiao, Shaobo', 'Fu, Zhenfang', 'Peng, Guiqing']",,,,
,PMC,Combination Attenuation Offers Strategy for Live Attenuated Coronavirus Vaccines,http://dx.doi.org/10.1128/JVI.00710-18,PMC6096805,,,"With an ongoing threat posed by circulating zoonotic strains, new strategies are required to prepare for the next emergent coronavirus (CoV). Previously, groups had targeted conserved coronavirus proteins as a strategy to generate live attenuated vaccine strains against current and future CoVs. With this in mind, we explored whether manipulation of CoV NSP16, a conserved 2′O methyltransferase (MTase), could provide a broad attenuation platform against future emergent strains. Using the severe acute respiratory syndrome-CoV mouse model, an NSP16 mutant vaccine was evaluated for protection from heterologous challenge, efficacy in the aging host, and potential for reversion to pathogenesis. Despite some success, concerns for virulence in the aged and potential for reversion makes targeting NSP16 alone an untenable approach. However, combining a 2′O MTase mutation with a previously described CoV fidelity mutant produced a vaccine strain capable of protection from heterologous virus challenge, efficacy in aged mice, and no evidence for reversion. Together, the results indicate that targeting the CoV 2′O MTase in parallel with other conserved attenuating mutations may provide a platform strategy for rapidly generating live attenuated coronavirus vaccines. IMPORTANCE Emergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed to stem future outbreaks. However, failure of many previous CoV vaccine formulations has clearly highlighted the need to test efficacy under different conditions and especially in vulnerable populations such as the aged and immunocompromised. This study illustrates that despite success in young models, the 2′O methyltransferase mutant carries too much risk for pathogenesis and reversion in vulnerable models to be used as a stand-alone vaccine strategy. Importantly, the 2′O methyltransferase mutation can be paired with other attenuating approaches to provide robust protection from heterologous challenge and in vulnerable populations. Coupled with increased safety and reduced pathogenesis, the study highlights the potential for 2′O methyltransferase attenuation as a major component of future live attenuated coronavirus vaccines.",,"['Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Mitchell, Hugh D.', 'Dinnon, Kenneth H.', 'Leist, Sarah R.', 'Yount, Boyd L.', 'McAnarney, Eileen T.', 'Graham, Rachel L.', 'Waters, Katrina M.', 'Baric, Ralph S.']",,,,
,PMC,Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43,http://dx.doi.org/10.1128/JVI.00404-18,PMC6096804,,,"Human coronaviruses (HCoVs) are recognized respiratory pathogens for which accumulating evidence indicates that in vulnerable patients the infection can cause more severe pathologies. HCoVs are not always confined to the upper respiratory tract and can invade the central nervous system (CNS) under still unclear circumstances. HCoV-induced neuropathologies in humans are difficult to diagnose early enough to allow therapeutic interventions. Making use of our already described animal model of HCoV neuropathogenesis, we describe the route of neuropropagation from the nasal cavity to the olfactory bulb and piriform cortex and then the brain stem. We identified neuron-to-neuron propagation as one underlying mode of virus spreading in cell culture. Our data demonstrate that both passive diffusion of released viral particles and axonal transport are valid propagation strategies used by the virus. We describe for the first time the presence along axons of viral platforms whose static dynamism is reminiscent of viral assembly sites. We further reveal that HCoV OC43 modes of propagation can be modulated by selected HCoV OC43 proteins and axonal transport. Our work, therefore, identifies processes that may govern the severity and nature of HCoV OC43 neuropathogenesis and will make possible the development of therapeutic strategies to prevent occurrences. IMPORTANCE Coronaviruses may invade the CNS, disseminate, and participate in the induction of neurological diseases. Their neuropathogenicity is being increasingly recognized in humans, and the presence and persistence of human coronaviruses (HCoV) in human brains have been proposed to cause long-term sequelae. Using our mouse model relying on natural susceptibility to HCoV OC43 and neuronal cell cultures, we have defined the most relevant path taken by HCoV OC43 to access and spread to and within the CNS toward the brain stem and spinal cord and studied in cell culture the underlying modes of intercellular propagation to better understand its neuropathogenesis. Our data suggest that axonal transport governs HCoV OC43 egress in the CNS, leading to the exacerbation of neuropathogenesis. Exploiting knowledge on neuroinvasion and dissemination will enhance our ability to control viral infection within the CNS, as it will shed light on underlying mechanisms of neuropathogenesis and uncover potential druggable molecular virus-host interfaces.",,"['Dubé, Mathieu', 'Le Coupanec, Alain', 'Wong, Alan H. M.', 'Rini, James M.', 'Desforges, Marc', 'Talbot, Pierre J.']",,,,
,PMC,AMP-activated Protein Kinase Phosphorylation of Angiotensin-Converting Enzyme 2 in Endothelium Mitigates Pulmonary Hypertension,http://dx.doi.org/10.1164/rccm.201712-2570OC,PMC6118028,,,"Rationale: Endothelial dysfunction plays an integral role in pulmonary hypertension (PH). AMPK (AMP-activated protein kinase) and ACE2 (angiotensin-converting enzyme 2) are crucial in endothelial homeostasis. The mechanism by which AMPK regulates ACE2 in the pulmonary endothelium and its protective role in PH remain elusive. Objectives: We investigated the role of AMPK phosphorylation of ACE2 Ser680 in ACE2 stability and deciphered the functional consequences of this post-translational modification of ACE2 in endothelial homeostasis and PH. Methods: Bioinformatics prediction, kinase assay, and antibody against phospho-ACE2 Ser680 (p-ACE2 S680) were used to investigate AMPK phosphorylation of ACE2 Ser680 in endothelial cells. Using CRISPR-Cas9 genomic editing, we created gain-of-function ACE2 S680D knock-in and loss-of-function ACE2 knockout (ACE2(−/−)) mouse lines to address the involvement of p-ACE2 S680 and ACE2 in PH. The AMPK–p-ACE2 S680 axis was also validated in lung tissue from humans with idiopathic pulmonary arterial hypertension. Measurements and Main Results: Phosphorylation of ACE2 by AMPK enhanced the stability of ACE2, which increased Ang (angiotensin) 1–7 and endothelial nitric oxide synthase–derived NO bioavailability. ACE2 S680D knock-in mice were resistant to PH as compared with wild-type littermates. In contrast, ACE2-knockout mice exacerbated PH, a similar phenotype found in mice with endothelial cell–specific deletion of AMPKα2. Consistently, the concentrations of phosphorylated AMPK, p-ACE2 S680, and ACE2 were decreased in human lungs with idiopathic pulmonary arterial hypertension. Conclusions: Impaired phosphorylation of ACE2 Ser680 by AMPK in pulmonary endothelium leads to a labile ACE2 and hence is associated with the pathogenesis of PH. Thus, AMPK regulation of the vasoprotective ACE2 is a potential target for PH treatment.",,"['Zhang, Jiao', 'Dong, Jianjie', 'Martin, Marcy', 'He, Ming', 'Gongol, Brendan', 'Marin, Traci L.', 'Chen, Lili', 'Shi, Xinxing', 'Yin, Yanjun', 'Shang, Fenqing', 'Wu, Yan', 'Huang, Hsi-Yuan', 'Zhang, Jin', 'Zhang, Yu', 'Kang, Jian', 'Moya, Esteban A.', 'Huang, Hsien-Da', 'Powell, Frank L.', 'Chen, Zhen', 'Thistlethwaite, Patricia A.', 'Yuan, Zu-Yi', 'Shyy, John Y.-J.']",,,,
,PMC,ACE2 and pACE2: A Pair of Aces for Pulmonary Arterial Hypertension Treatment?,http://dx.doi.org/10.1164/rccm.201803-0569ED,PMC6118027,,,,,"['Richards, Elaine M.', 'Raizada, Mohan K.']",,,,
,PMC,Collagen type V a2 (COL5A2) is decreased in steroid-induced necrosis of the femoral head,,PMC6129523,,,"Collagen is essential for bone adhesion and formation. In the present study, proteomic analysis suggested that collagen type V a2 (COL5A2) was significantly decreased in the necrotic area of patients with steroid-induced necrosis of the femoral head (ONFH). In vitro, the effects of methylprednisolone (MP) on the proliferation and differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) were investigated. The expression of the osteogenic-related proteins, Runx2, alkaline phosphatase (ALP), osteocalcin (OC) and COL5A2 was significantly downregulated post-MP treatment. In vivo analyses revealed that post-MP treatment, rats showed typical signs of ONFH by micro-CT scanning and hematoxylin and eosin (H&E) staining. Immunohistochemical staining demonstrated that the expression of COL5A2 and vascular endothelial growth factor (VEGF) was significantly decreased post-MP treatment. In conclusion, the expression COL5A2 was lower in patients with steroid-induced ONFH, hence COL5A2 may be a promising therapeutic target for steroid induced ONFH treatment.",,"['Yang, Fan', 'Luo, Pengbo', 'Ding, Hao', 'Zhang, Changqing', 'Zhu, Zhenhong']",,,,
,PMC,The Great Opportunity: Cultivating Scientific Inquiry in Medical Residency,http://dx.doi.org/10.1093/infdis/jiy200,PMC6093444,,,"Residency training is a profound experience that greatly influences the career trajectory of every trainee. Currently, residency programs focus heavily (or almost exclusively) on the acquisition of medical knowledge and fail to foster intellectual curiosity and introduce residents to careers in investigation. We share 3 programs embedded in residency training where this focus is shifted with an emphasis on prompting intellectual curiosity and exciting residents about careers in investigation to revitalize the physician-scientist workforce.",,"['Vyas, Jatin M', 'Rajagopal, Jayaraj', 'Sokol, Caroline L', 'Wein, Marc N', 'Mansour, Michael K', 'Corey, Kathleen E', 'Fishman, Mark C', 'Armstrong, Katrina A']",,,,
,PMC,The Damage–Response Framework as a Tool for the Physician-Scientist to Understand the Pathogenesis of Infectious Diseases,http://dx.doi.org/10.1093/infdis/jiy083,PMC6093430,,,"The Damage–Response Framework (DRF) is a powerful tool to inform research in infectious diseases. It can integrate clinical observation with microbiology and immunology to incorporate the role of the host response into the outcome of microbial pathogenesis. Although the role that microbial factors may play in the pathogenesis of infectious diseases is well recognized, the DRF brings the indispensable role of the host response to the fore. For example, inflammation may induce microbial control, but it can also produce host damage. On the other hand, insufficient inflammation may fail to induce sufficient microbial control. Each scenario may lead to the diagnosis of an infectious disease. Given the central role that the host response plays in the pathogenesis of infectious diseases, new strategies for treatment need to consider the nature of the host response as well as microbial factors.",,"['Pirofski, Liise-anne', 'Casadevall, Arturo']",,,,
,PMC,Functional plasticity of antibacterial EndoU toxins,http://dx.doi.org/10.1111/mmi.14007,PMC6173971,,,"Bacteria use several different secretion systems to deliver toxic EndoU ribonucleases into neighboring cells. Here, we present the first structure of a prokaryotic EndoU toxin in complex with its cognate immunity protein. The contact-dependent growth inhibition toxin CdiA-CT(STECO31) from Escherichia coli STEC_O31 adopts the eukaryotic EndoU fold and shares greatest structural homology with the nuclease domain of coronavirus Nsp15. The toxin contains a canonical His-His-Lys catalytic triad in the same arrangement as eukaryotic EndoU domains, but lacks the uridylate-specific ribonuclease activity that characterizes the superfamily. Comparative sequence analysis indicates that bacterial EndoU domains segregate into at least three major clades based on structural variations in the N-terminal subdomain. Representative EndoU nucleases from clades I and II degrade tRNA molecules with little specificity. In contrast, CdiA-CT(STECO31) and other clade III toxins are specific anticodon nucleases that cleave tRNA(Glu) between nucleotides C37 and m(2)A38. These findings suggest that the EndoU fold is a versatile scaffold for the evolution of novel substrate specificities. Such functional plasticity may account for the widespread use of EndoU effectors by diverse inter-bacterial toxin delivery systems.",,"['Michalska, Karolina', 'Nhan, Dinh Quan', 'Willett, Julia L. E.', 'Stols, Lucy M.', 'Eschenfeldt, William H.', 'Jones, Allison M.', 'Nguyen, Josephine Y.', 'Koskiniemi, Sanna', 'Low, David A.', 'Goulding, Celia W.', 'Joachimiak, Andrzej', 'Hayes, Christopher S.']",,,,
,PMC,Comprehensive Proteomics Identification of IFN-λ3-regulated Antiviral Proteins in HBV-transfected Cells,http://dx.doi.org/10.1074/mcp.RA118.000735,PMC6210224,,,"Interferon lambda (IFN-λ) is a relatively unexplored, yet promising antiviral agent. IFN-λ has recently been tested in clinical trials of chronic hepatitis B virus infection (CHB), with the advantage that side effects may be limited compared with IFN-α, as IFN-λ receptors are found only in epithelial cells. To date, IFN-λ's downstream signaling pathway remains largely unelucidated, particularly via proteomics methods. Here, we report that IFN-λ3 inhibits HBV replication in HepG2.2.15 cells, reducing levels of both HBV transcripts and intracellular HBV DNA. Quantitative proteomic analysis of HBV-transfected cells was performed following 24-hour IFN-λ3 treatment, with parallel IFN-α2a and PBS treatments for comparison using a dimethyl labeling method. The depth of the study allowed us to map the induction of antiviral proteins to multiple points of the viral life cycle, as well as facilitating the identification of antiviral proteins not previously known to be elicited upon HBV infection (e.g. IFITM3, XRN2, and NT5C3A). This study also shows up-regulation of many effectors involved in antigen processing/presentation indicating that this cytokine exerted immunomodulatory effects through several essential molecules for these processes. Interestingly, the 2 subunits of the immunoproteasome cap (PSME1 and PSME2) were up-regulated whereas cap components of the constitutive proteasome were down-regulated upon both IFN treatments, suggesting coordinated modulation toward the antigen processing/presentation mode. Furthermore, in addition to confirming canonical activation of interferon-stimulated gene (ISG) transcription through the JAK-STAT pathway, we reveal that IFN-λ3 restored levels of RIG-I and RIG-G, proteins known to be suppressed by HBV. Enrichment analysis demonstrated that several biological processes including RNA metabolism, translation, and ER-targeting were differentially regulated upon treatment with IFN-λ3 versus IFN-α2a. Our proteomic data suggests that IFN-λ3 regulates an array of cellular processes to control HBV replication.",,"['Makjaroen, Jiradej', 'Somparn, Poorichaya', 'Hodge, Kenneth', 'Poomipak, Witthaya', 'Hirankarn, Nattiya', 'Pisitkun, Trairak']",,,,
,PMC,NAADP-dependent Ca(2+) signaling regulates Middle East Respiratory Syndrome-Coronavirus pseudovirus translocation through the endolysosomal system,http://dx.doi.org/10.1016/j.ceca.2018.08.003,PMC6251489,,,"Middle East Respiratory Syndrome coronavirus (MERS-CoV) infections are associated with a significant mortality rate, and existing drugs show poor efficacy. Identifying novel targets/pathways required for MERS infectivity is therefore important for developing novel therapeutics. As an enveloped virus, translocation through the endolysosomal system provides one pathway for cellular entry of MERS-CoV. In this context, Ca(2+)-permeable channels within the endolysosomal system regulate both the luminal environment and trafficking events, meriting investigation of their role in regulating processing and trafficking of MERS-CoV. Knockdown of endogenous two-pore channels (TPCs), targets for the Ca(2+) mobilizing second messenger NAADP, impaired infectivity in a MERS-CoV spike pseudovirus particle translocation assay. This effect was selective as knockdown of the lysosomal cation channel mucolipin-1 (TRPML1) was without effect. Pharmacological inhibition of NAADP-evoked Ca(2+) release using several bisbenzylisoquinoline alkaloids also blocked MERS pseudovirus translocation. Knockdown of TPC1 (biased endosomally) or TPC2 (biased lysosomally) decreased the activity of furin, a protease which facilitates MERS fusion with cellular membranes. Pharmacological or genetic inhibition of TPC1 activity also inhibited endosomal motility impairing pseudovirus progression through the endolysosomal system. Overall, these data support a selective, spatially autonomous role for TPCs within acidic organelles to support MERS-CoV translocation.",,"['Gunaratne, Gihan S.', 'Yang, Yang', 'Li, Fang', 'Walseth, Timothy F.', 'Marchant, Jonathan S.']",,,,
,PMC,Prospects for a MERS-CoV spike vaccine,http://dx.doi.org/10.1080/14760584.2018.1506702,PMC6355461,,,"INTRODUCTION: Six years have passed since Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV), a newly emerging infectious virus, was first reported in 2012. Although MERS-CoV has had a consistently high mortality rate in humans, no vaccines have been approved to prevent MERS-CoV infection in humans. MERS-CoV spike (S) protein is a key target for development of MERS vaccines. AREAS COVERED: In this review, we illustrate the structure and function of S protein as a vaccine target, describe available animal models for evaluating MERS vaccines, and summarize recent progress on MERS-CoV S-based vaccines, focusing on their ability to elicit antibody and/or cellular immune responses, neutralizing antibodies, and protection against MERS-CoV infection in different models. Prospects for future MERS-CoV S-based vaccines are discussed. EXPERT COMMENTARY: The majority of MERS vaccines under development are based on MERS-CoV S protein, including full-length S, S1, and receptor-binding domain (RBD). While it is essential to evaluate the safety of full-length S and S1-based MERS vaccines, further improvement of the efficacy of RBD-based vaccines using novel strategies would be necessary. Overall, this review provides informative guidance for designing and developing safe and effective MERS vaccines based on viral S protein.",,"['Zhou, Yusen', 'Jiang, Shibo', 'Du, Lanying']",,,,
,PMC,Nicotine and the renin-angiotensin system,http://dx.doi.org/10.1152/ajpregu.00099.2018,PMC6295500,,,"Cigarette smoking is the single most important risk factor for the development of cardiovascular and pulmonary diseases (CVPD). Although cigarette smoking has been in constant decline since the 1950s, the introduction of e-cigarettes or electronic nicotine delivery systems 10 yr ago has attracted former smokers as well as a new generation of consumers. Nicotine is a highly addictive substance, and it is currently unclear whether e-cigarettes are “safer” than regular cigarettes or whether they have the potential to reverse the health benefits, notably on the cardiopulmonary system, acquired with the decline of tobacco smoking. Of great concern, nicotine inhalation devices are becoming popular among young adults and youths, emphasizing the need for awareness and further study of the potential cardiopulmonary risks of nicotine and associated products. This review focuses on the interaction between nicotine and the renin-angiotensin system (RAS), one of the most important regulatory systems on autonomic, cardiovascular, and pulmonary functions in both health and disease. The literature presented in this review strongly suggests that nicotine alters the homeostasis of the RAS by upregulating the detrimental angiotensin-converting enzyme (ACE)/angiotensin (ANG)-II/ANG II type 1 receptor axis and downregulating the compensatory ACE2/ANG-(1–7)/Mas receptor axis, contributing to the development of CVPD.",,"['Oakes, Joshua M.', 'Fuchs, Robert M.', 'Gardner, Jason D.', 'Lazartigues, Eric', 'Yue, Xinping']",,,,
,PMC,INITIAL HIGH VIRAL LOAD IS ASSOCIATED WITH PROLONGED SHEDDING OF HUMAN RHINOVIRUS IN ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT RECIPIENTS,http://dx.doi.org/10.1016/j.bbmt.2018.07.006,PMC6239940,,,"INTRODUCTION: Recent data suggest human rhinovirus (HRV) is associated with lower respiratory tract infection and mortality in hematopoietic cell transplant (HCT) recipients. Examining risk factors for prolonged viral shedding may provide critical insight for the development of novel therapeutics and help inform infection prevention practices. Our objective was to identify risk factors for prolonged shedding of HRV post-HCT. MATERIALS AND METHODS: We prospectively collected weekly nasal samples from allogeneic HCT recipients from day 0 to day 100 post-transplant, and performed realtime RT-PCR (12/2005 to 2/2010). Subjects with symptomatic HRV infection and a negative test within 2 weeks of the last positive were included. Duration of shedding was defined as time between the first positive and first negative samples. Cycle threshold (Ct) values were used as a proxy for viral load. HRV species were identified by sequencing the 5’ non-coding region. Logistic regression analyses were performed to evaluate factors associated with prolonged shedding (≥21 days). RESULTS: We identified 38 HCT recipients with HRV infection fulfilling study criteria (32 adults, 6 children). Median duration of shedding was 9.5 days (2-89 days); 18 patients had prolonged shedding. Among 26 samples sequenced, 69% were species A, and species B and C accounted for 15% each; the median shedding duration of HRV did not differ between species (P = 0.17). Bivariable logistic regression analyses suggest that initial high viral load (low Ct value) is associated with prolonged shedding. CONCLUSIONS: HCT recipients with initial high viral loads are at risk for prolonged HRV viral shedding.",,"['Ogimi, Chikara', 'Xie, Hu', 'Leisenring, Wendy M', 'Kuypers, Jane M', 'Jerome, Keith R', 'Campbell, Angela P.', 'Englund, Janet A', 'Boeckh, Michael', 'Waghmare, Alpana']",,,,
,PMC,Precision Surveillance for Viral Respiratory Pathogens: Virome Capture Sequencing for the Detection and Genomic Characterization of Severe Acute Respiratory Infection in Uganda,http://dx.doi.org/10.1093/cid/ciy656,PMC6424078,,,"BACKGROUND: Precision public health is a novel set of methods to target disease prevention and mitigation interventions to high-risk subpopulations. We applied a precision public health strategy to syndromic surveillance for severe acute respiratory infection (SARI) in Uganda by combining spatiotemporal analytics with genomic sequencing to detect and characterize viral respiratory pathogens with epidemic potential. METHODS: Using a national surveillance network we identified patients with unexplained, influenza-negative SARI from 2010 to 2015. Spatiotemporal analyses were performed retrospectively to identify clusters of unexplained SARI. Within clusters, respiratory viruses were detected and characterized in naso- and oropharyngeal swab samples using a novel oligonucleotide probe capture (VirCapSeq-VERT) and high-throughput sequencing platform. Linkage to conventional epidemiologic strategies further characterized transmission dynamics of identified pathogens. RESULTS: Among 2901 unexplained SARI cases, 9 clusters were detected, accounting for 301 (10.4%) cases. Clusters were more likely to occur in urban areas and during biannual rainy seasons. Within detected clusters, we identified an unrecognized outbreak of measles-associated SARI; sequence analysis implicated cocirculation of endemic genotype B3 and genotype D4 likely imported from England. We also detected a likely nosocomial SARI cluster associated with a novel picobirnavirus most closely related to swine and dromedary viruses. CONCLUSIONS: Using a precision approach to public health surveillance, we detected and characterized the genomics of vaccine-preventable and zoonotic respiratory viruses associated with clusters of severe respiratory infections in Uganda. Future studies are needed to assess the feasibility, scalability, and impact of applying similar approaches during real-time public health surveillance in low-income settings.",,"['Cummings, Matthew J', 'Tokarz, Rafal', 'Bakamutumaho, Barnabas', 'Kayiwa, John', 'Byaruhanga, Timothy', 'Owor, Nicholas', 'Namagambo, Barbara', 'Wolf, Allison', 'Mathema, Barun', 'Lutwama, Julius J', 'Schluger, Neil W', 'Lipkin, W Ian', 'O’Donnell, Max R']",,,,
,PMC,Feed batch sequencing to decrease the risk of porcine epidemic diarrhea virus (PEDV) cross-contamination during feed manufacturing,http://dx.doi.org/10.1093/jas/sky320,PMC6247855,,,"Feed has been identified as a vector of transmission for porcine epidemic diarrhea virus (PEDV). The objective of this study was to determine if feed batch sequencing methods could minimize PEDV cross-contamination. Porcine epidemic diarrhea virus-free swine feed was manufactured to represent the negative control. A 50 kg feed batch was mixed in a pilot scale feed mill for 5 min, sampled, then discharged for 10 min into a bucket elevator and sampled again upon exit. Next, a pathogenic PEDV isolate was used to inoculate 49.5 kg of PEDV-free feed to form the positive control. The positive control was mixed, conveyed and sampled similar to the negative control. Subsequently, 4 sequence batches (sequence 1 to 4) were formed by adding a 50 kg batch of PEDV-negative feed to the mixer after the prior batch was mixed and conveyed; all sequences were mixed, conveyed, and sampled similar to the negative and positive control batches. None of the equipment was cleaned between batches within a replicate. This entire process was replicated 3 times with cleaning the feed mill between replicates. Feed was then analyzed for PEDV RNA by real-time reverse transcriptase semiquantitative polymerase chain reaction (rRT-PCR) as measured by cycle threshold (Ct) and for infectivity by bioassay. Sequence 1 feed had higher (P ˂ 0.05) rRT-PCR Ct values than the positive batch and sequence 2 feed had higher (P ˂ 0.05) Ct values than sequence 1, regardless of sampled location. Feed sampled from the mixer from sequence 2, 3, and 4 was rRT-PCR negative whereas feed sampled from the bucket elevator was rRT-PCR negative from sequence 3 and 4. Bioassay was conducted using 66 mixed sex 10-d-old pigs confirmed negative for PEDV allocated to 22 different rooms. Pigs were initially 10-d old. Control pigs remained PEDV negative for the study. All pigs from the mixer positive batch (9/9) and bucket elevator positive batch (3/3) were rRT-PCR positive on fecal swabs by the end of the study. One replicate of pigs from mixer sequence 1 was rRT-PCR positive (3/3) by 7 dpi. One replicate of mixer pigs from sequence 2 was rRT-PCR positive (3/3) by 7 dpi although no detectable PEDV RNA was found in the feed. The results demonstrate sequenced batches had reduced quantities of PEDV RNA although sequenced feed without detectible PEDV RNA by rRT-PCR can be infectious. Therefore, a sequencing protocol can reduce but not eliminate the risk of producing infectious PEDV carryover from the first sequenced batch of feed.",,"['Schumacher, Loni L', 'Cochrane, Roger A', 'Huss, Anne R', 'Gebhardt, Jordan T', 'Woodworth, Jason C', 'Stark, Charles R', 'Jones, Cassandra K', 'Bai, Jianfa', 'Main, Rodger G', 'Chen, Qi', 'Zhang, Jianqiang', 'Gauger, Philip C', 'DeRouchey, Joel M', 'Goodband, Robert D', 'Tokach, Mike D', 'Dritz, Steve S']",,,,
,PMC,Strategies to Reduce the Immunogenicity of Recombinant Immunotoxins,http://dx.doi.org/10.1016/j.ajpath.2018.04.016,PMC6099333,,,"Recombinant immunotoxins (RITs) are genetically engineered proteins being developed to treat cancer. They are composed of an Fv that targets a cancer antigen and a fragment of a bacterial toxin that kills tumor cells. Because the toxin is a foreign protein, it is immunogenic. The clinical success of RITs in patients with a normal immune system is limited by their immunogenicity. In this review, we discuss our progress in therapeutic protein deimmunization and the balancing act between immunogenicity and therapeutic potency. One approach is to prevent the activation of B cells by mapping and elimination of B-cell epitopes. A second approach is to prevent helper T-cell activation by interfering with major histocompatibility complex II presentation or T-cell recognition. Immunizing mice with RITs that were deimmunized by elimination of the murine B- or T-cell epitopes showed that both approaches are effective. Another approach to control immunogenicity is to modify the host immune system. Nanoparticles containing synthetic vaccine particles encapsulating rapamycin can induce immune tolerance and prevent anti-drug antibody formation. This treatment restores RIT anti-tumor activity that is otherwise neutralized because of immunogenicity.",,"['Mazor, Ronit', 'King, Emily M.', 'Pastan, Ira']",,,,
,PMC,Cerebral toxoplasmosis in a cat with feline leukemia and feline infectious peritonitis viral infections,,PMC6049326,,,"A diarrheic young cat died after neurological involvement. Biochemistry pointed to feline infectious peritonitis (FIP). The final diagnosis was severe multifocal meningoencephalitis due to Toxoplasma gondii. The presence of the parasite in the brain was confirmed using immunohistochemical staining. Concomitant feline leukemia virus (FeLV) and FIP were possible contributors to the clinical, fatal outcome.",,"['Zandonà, Luca', 'Brunetta, Romina', 'Zanardello, Claudia', 'Vascellari, Marta', 'Persico, Luca', 'Mazzolini, Elena']",,,,
,PMC,Translation Elongation and Recoding in Eukaryotes,http://dx.doi.org/10.1101/cshperspect.a032649,PMC6071482,,,"In this review, we highlight the current understanding of translation elongation and recoding in eukaryotes. In addition to providing an overview of the process, recent advances in our understanding of the role of the factor eIF5A in both translation elongation and termination is discussed. We also highlight mechanisms of translation recoding with a focus on ribosomal frameshifting during elongation. We see that the balance between the basic steps in elongation and the less common recoding events is determined by the kinetics of the different processes as well as by specific sequence determinants.",,"['Dever, Thomas E.', 'Dinman, Jonathan D.', 'Green, Rachel']",,,,
,PMC,Application of albumin/globulin ratio in elderly patients with acute exacerbation of chronic obstructive pulmonary disease,http://dx.doi.org/10.21037/jtd.2018.07.47,PMC6129906,,,"BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has become an important disease of hospitalized elderly patients, which lack simple and inexpensive indicators for evaluating the condition and prognosis. This study was performed to investigate the clinical significance of the serum albumin/globulin ratio (AGR) in elderly patients with AECOPD. METHODS: The data of 252 hospitalized elderly patients with AECOPD, 89 stable COPD patients and 115 elderly healthy individuals were analyzed and compared. The differences in the AGR, logarithm of the serum C-reactive protein (LogCRP) level, prealbumin (PA) level, and immunoglobulin G (IgG) level were compared. AECOPD patients were grouped using the optimal cutoff values of each index to compare the difference in the combined infection rate. The correlation between hospital stays and AGR was analyzed. RESULTS: The AGR, LogCRP, PA level, and IgG level were different among the AECOPD group, stable COPD group and healthy control groups (P<0.05). The AGR, LogCRP, and PA level were different (P<0.05) among the Global Initiative for Chronic Obstructive Lung Disease (GOLD) I, II, II, and IV groups. Age, AGR, LogCRP, and PA level were different (P<0.05) between the infection and non-infection groups. After grouping according to the optimal cutoff values, the combined infection rate was different (P<0.05). The AGR was negatively correlated with the hospital stay (r=−0.583, P<0.001). The hospital stay was longer in patients with an AGR of <1.37 than ≥1.37 (P<0.001). CONCLUSIONS: The AGR can be regarded as a reference index for evaluating the condition of elderly patients with AECOPD, determining the presence of combined infection, and predicting the prognosis.",,"['Qin, Jinqiu', 'Qin, Yuanyuan', 'Wu, Yangyang', 'Wei, Aiqiu', 'Luo, Meiling', 'Liao, Lin', 'Lin, Faquan']",,,,
,PMC,Pharmacologic Depletion of Microglia Increases Viral Load in the Brain and Enhances Mortality in Murine Models of Flavivirus-Induced Encephalitis,http://dx.doi.org/10.1128/JVI.00525-18,PMC6069207,,,"Flaviviruses account for most arthropod-borne cases of human encephalitis in the world. However, the exact mechanisms of injury to the central nervous system (CNS) during flavivirus infections remain poorly understood. Microglia are the resident immune cells of the CNS and are important for multiple functions, including control of viral pathogenesis. Utilizing a pharmacologic method of microglia depletion (PLX5622 [Plexxikon Inc.], an inhibitor of colony-stimulating factor 1 receptor), we sought to determine the role of microglia in flaviviral pathogenesis. Depletion of microglia resulted in increased mortality and viral titer in the brain following infection with either West Nile virus (WNV) or Japanese encephalitis virus (JEV). Interestingly, microglial depletion did not prevent virus-induced increases in the expression of relevant cytokines and chemokines at the mRNA level. In fact, the expression of several proinflammatory genes was increased in virus-infected, microglia-depleted mice compared to virus-infected, untreated controls. In contrast, and as expected, expression of the macrophage marker triggering receptor expressed on myeloid cells 2 (TREM2) was decreased in virus-infected, PLX5622-treated mice compared to virus-infected controls. IMPORTANCE As CNS invasion by flaviviruses is a rare but life-threatening event, it is critical to understand how brain-resident immune cells elicit protection or injury during disease progression. Microglia have been shown to be important in viral clearance but may also contribute to CNS injury as part of the neuroinflammatory process. By utilizing a microglial depletion model, we can begin to parse out the exact roles of microglia during flaviviral pathogenesis with hopes of understanding specific mechanisms as potential targets for therapeutics.",,"['Seitz, Scott', 'Clarke, Penny', 'Tyler, Kenneth L.']",,,,
,PMC,Porcine Reproductive and Respiratory Syndrome Virus Infection Induces both eIF2α Phosphorylation-Dependent and -Independent Host Translation Shutoff,http://dx.doi.org/10.1128/JVI.00600-18,PMC6069200,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has caused tremendous economic losses in the global swine industry since it was discovered in the late 1980s. Inducing host translation shutoff is a strategy used by many viruses to optimize their replication and spread. Here, we demonstrate that PRRSV infection causes host translation suppression, which is strongly dependent on viral replication. By screening PRRSV-encoded nonstructural proteins (nsps), we found that nsp2 participates in the induction of host translation shutoff and that its transmembrane (TM) domain is required for this process. nsp2-induced translation suppression is independent of protein degradation pathways and the phosphorylation of eukaryotic initiation factor 2α (eIF2α). However, the overexpression of nsp2 or its TM domain significantly attenuated the mammalian target of rapamycin (mTOR) signaling pathway, an alternative pathway for modulating host gene expression. PRRSV infection also attenuated the mTOR signaling pathway, and PRRSV-induced host translation shutoff could be partly reversed when the attenuated mTOR phosphorylation was reactivated by an activator of the mTOR pathway. PRRSV infection still negatively regulated the host translation when the effects of eIF2α phosphorylation were completely reversed. Taken together, our results demonstrate that PRRSV infection induces host translation shutoff and that nsp2 is associated with this process. Both eIF2α phosphorylation and the attenuation of the mTOR signaling pathway contribute to PRRSV-induced host translation arrest. IMPORTANCE Viruses are obligate parasites, and the production of progeny viruses relies strictly on the host translation machinery. Therefore, the efficient modulation of host mRNA translation benefits viral replication, spread, and evolution. In this study, we provide evidence that porcine reproductive and respiratory syndrome virus (PRRSV) infection induces host translation shutoff and that the viral nonstructural protein nsp2 is associated with this process. Many viruses induce host translation shutoff by phosphorylating eukaryotic initiation factor 2α (eIF2α). However, PRRSV nsp2 does not induce eIF2α phosphorylation but attenuates the mTOR signaling pathway, another pathway regulating the host cell translational machinery. We also found that PRRSV-induced host translation shutoff was partly reversed by eliminating the effects of eIF2α phosphorylation or reactivating the mTOR pathway, indicating that PRRSV infection induces both eIF2α phosphorylation-dependent and -independent host translation shutoff.",,"['Li, Yang', 'Fang, Liurong', 'Zhou, Yanrong', 'Tao, Ran', 'Wang, Dang', 'Xiao, Shaobo']",,,,
,PMC,Design of Novel HIV-1/2 Fusion Inhibitors with High Therapeutic Efficacy in Rhesus Monkey Models,http://dx.doi.org/10.1128/JVI.00775-18,PMC6069194,,,"T-20 (enfuvirtide) is the only approved viral fusion inhibitor that is used for the treatment of human immunodeficiency virus type 1 (HIV-1) infection; however, it has relatively low antiviral activity and easily induces drug resistance. We recently reported a T-20-based lipopeptide fusion inhibitor (LP-40) showing improved anti-HIV activity (X. Ding et al., J Virol 91:e00831-17, 2017, https://doi.org/10.1128/JVI.00831-17). In this study, we designed LP-50 and LP-51 by refining the structure and function of LP-40. The two new lipopeptides showed dramatically enhanced secondary structure and binding stability and were exceptionally potent inhibitors of HIV-1, HIV-2, simian immunodeficiency virus (SIV), and chimeric simian-human immunodeficiency virus (SHIV), with mean 50% inhibitory concentrations (IC(50)s) in the very low picomolar range. They also exhibited dramatically increased potencies in inhibiting a panel of T-20- and LP-40-resistant mutant viruses. In line with their in vitro data, LP-50 and LP-51 exhibited extremely potent and long-lasting ex vivo anti-HIV activities in rhesus monkeys: serum dilution peaks that inhibited 50% of virus infection were >15,200-fold higher than those for T-20 and LP-40. Low-dose, short-term monotherapy of LP-51 could sharply reduce viral loads to undetectable levels in acutely and chronically SHIV infected monkey models. To our knowledge, LP-50 and LP-51 are the most potent and broad HIV-1/2 and SIV fusion inhibitors, which can be developed for clinical use and can serve as tools for exploration of the mechanisms of viral entry and inhibition. IMPORTANCE T-20 remains the only membrane fusion inhibitor available for the treatment of viral infection, but its relatively low anti-HIV activity and genetic barrier for drug resistance have significantly limited its clinical application. Here we report two new lipopeptide-based fusion inhibitors (LP-50 and LP-51) showing extremely potent inhibitory activities against diverse HIV-1, HIV-2, SIV, and T-20-resistant variants. Promisingly, both inhibitors exhibited potent and long-lasting ex vivo anti-HIV activity and could efficiently suppress viral loads to undetectable levels in SHIV-infected monkey models. We believe that LP-50 and LP-51 are the most potent and broad-spectrum fusion inhibitors known to date and thus have high potential for clinical development.",,"['Chong, Huihui', 'Xue, Jing', 'Zhu, Yuanmei', 'Cong, Zhe', 'Chen, Ting', 'Guo, Yan', 'Wei, Qiang', 'Zhou, Yusen', 'Qin, Chuan', 'He, Yuxian']",,,,
,PMC,Ulk1 Governs Nerve Growth Factor/TrkA Signaling by Mediating Rab5 GTPase Activation in Porcine Hemagglutinating Encephalomyelitis Virus-Induced Neurodegenerative Disorders,http://dx.doi.org/10.1128/JVI.00325-18,PMC6069187,,,"Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurovirulent coronavirus and causes neurological dysfunction in the central nervous system (CNS), but the neuropathological mechanism of PHEV remains poorly understood. We report that Unc51-like kinase 1 (Ulk1/Unc51.1) is a pivotal regulator of PHEV-induced neurological disorders and functions to selectively control the initiation of nerve growth factor (NGF)/TrkA endosome trafficking. We first identified the function of Ulk1 by histopathologic evaluation in a PHEV-infected mouse model in which neuronal loss was accompanied by the suppression of Ulk1 expression. Morphogenesis assessments in the primary cortical neurons revealed that overexpression or mutations of Ulk1 modulated neurite outgrowth, collateral sprouting, and endosomal transport. Likewise, Ulk1 expression was decreased following PHEV infection, suggesting that there was a correlation between the neurodegeneration and functional Ulk1 deficiency. We then showed that Ulk1 forms a multiprotein complex with TrkA and the early endosome marker Rab5 and that Ulk1 defects lead to either blocking of NGF/TrkA endocytosis or premature degradation of pTrkA via constitutive activation of the Rab5 GTPase. Further investigation determined that the ectopic expression of Rab5 mutants induces aberrant endosomal accumulation of activated pTrkA, proving that targeting of Ulk1-TrkA-NGF signaling to the retrograde transport route in the neurodegenerative process that underlies PHEV infection is dependent on Rab5 GTPase activity. Therefore, we described a long-distance signaling mechanism of PHEV-driven deficits in neurons and suggested that such Ulk1 repression may result in limited NGF/TrkA retrograde signaling within activated Rab5 endosomes, explaining the progressive failure of neurite outgrowth and survival. IMPORTANCE Porcine hemagglutinating encephalomyelitis virus (PHEV) is a neurotropic coronavirus and targets neurons in the nervous system for proliferation, frequently leaving behind grievous neurodegeneration. Structural plasticity disorders occur in the axons, dendrites, and dendritic spines of PHEV-infected neurons, and dysfunction of this neural process may contribute to neurologic pathologies, but the mechanisms remain undetermined. Further understanding of the neurological manifestations underlying PHEV infection in the CNS may provide insights into both neurodevelopmental and neurodegenerative diseases that may be conducive to targeted approaches for treatment. The significance of our research is in identifying an Ulk1-related neurodegenerative mechanism, focusing on the regulatory functions of Ulk1 in the transport of long-distance trophic signaling endosomes, thereby explaining the progressive failure of neurite outgrowth and survival associated with PHEV aggression. This is the first report to define a mechanistic link between alterations in signaling from endocytic pathways and the neuropathogenesis of PHEV-induced CNS disease.",,"['Li, Zi', 'Zhao, Kui', 'Lv, Xiaoling', 'Lan, Yungang', 'Hu, Shiyu', 'Shi, Junchao', 'Guan, Jiyu', 'Yang, Yawen', 'Lu, Huijun', 'He, Hongbin', 'Gao, Feng', 'He, Wenqi']",,,,
,PMC,HIV-1 Protease Evolvability Is Affected by Synonymous Nucleotide Recoding,http://dx.doi.org/10.1128/JVI.00777-18,PMC6069183,,,"One unexplored aspect of HIV-1 genetic architecture is how codon choice influences population diversity and evolvability. Here we compared the levels of development of HIV-1 resistance to protease inhibitors (PIs) between wild-type (WT) virus and a synthetic virus (MAX) carrying a codon-pair-reengineered protease sequence including 38 (13%) synonymous mutations. The WT and MAX viruses showed indistinguishable replication in MT-4 cells or peripheral blood mononuclear cells (PBMCs). Both viruses were subjected to serial passages in MT-4 cells, with selective pressure from the PIs atazanavir (ATV) and darunavir (DRV). After 32 successive passages, both the WT and MAX viruses developed phenotypic resistance to PIs (50% inhibitory concentrations [IC(50)s] of 14.6 ± 5.3 and 21.2 ± 9 nM, respectively, for ATV and 5.9 ± 1.0 and 9.3 ± 1.9, respectively, for DRV). Ultradeep sequence clonal analysis revealed that both viruses harbored previously described mutations conferring resistance to ATV and DRV. However, the WT and MAX virus proteases showed different resistance variant repertoires, with the G16E and V77I substitutions observed only in the WT and the L33F, S37P, G48L, Q58E/K, and L89I substitutions detected only in the MAX virus. Remarkably, the G48L and L89I substitutions are rarely found in vivo in PI-treated patients. The MAX virus showed significantly higher nucleotide and amino acid diversity of the propagated viruses with and without PIs (P < 0.0001), suggesting a higher selective pressure for change in this recoded virus. Our results indicate that the HIV-1 protease position in sequence space delineates the evolution of its mutant spectrum. Nevertheless, the investigated synonymously recoded variant showed mutational robustness and evolvability similar to those of the WT virus. IMPORTANCE Large-scale synonymous recoding of virus genomes is a new tool for exploring various aspects of virus biology. Synonymous virus genome recoding can be used to investigate how a virus's position in sequence space defines its mutant spectrum, evolutionary trajectory, and pathogenesis. In this study, we evaluated how synonymous recoding of the human immunodeficiency virus type 1 (HIV-1) protease affects the development of protease inhibitor (PI) resistance. HIV-1 protease is a main target of current antiretroviral therapies. Our present results demonstrate that the wild-type (WT) virus and a virus with recoded protease exhibited different patterns of resistance mutations after PI treatment. Nevertheless, the developed PI resistance phenotypes were indistinguishable between the recoded virus and the WT virus, suggesting that the HIV-1 strain with synonymously recoded protease and the WT virus are equally robust and evolvable.",,"['Nevot, Maria', 'Jordan-Paiz, Ana', 'Martrus, Glòria', 'Andrés, Cristina', 'García-Cehic, Damir', 'Gregori, Josep', 'Franco, Sandra', 'Quer, Josep', 'Martinez, Miguel Angel']",,,,
,PMC,Astrovirus infections induce age-dependent dysbiosis in gut microbiomes of bats,http://dx.doi.org/10.1038/s41396-018-0239-1,PMC6246552,,,"Astroviruses (AstV) are a major cause of diarrhoea in children. Interestingly, some wildlife species, including bats, remain phenotypically asymptomatic after infection. Disease symptoms, however, may only be less visible in bats and enteric viruses may indeed perturb their gut microbial communities. Gut microbiomes represent an important driver of immune defence mechanisms but potential effects of enteric virus-host microbiome interactions are largely unexplored. Using bats as a natural model system, we show that AstV-infections affect the gut microbiome, with the strength of the effect depending on host age. The gut microbial α- and β-diversity and the predicted microbial functional orthologs decreased in young bats but surprisingly increased in adult AstV + bats. The abundance of bacterial taxa characteristic for healthy microbiomes was strongly reduced in young AstV+ bats, possibly attributable to their immature immune system. Regardless of age, pathogen-containing genera exhibited negative interactions with several commensal taxa and increased after AstV-infection, leading to pathobiont-like shifts in the gut microbiome of all infected bats. Thus, in apparently healthy bats, AstV-infections disturb gut bacterial homeostasis, possibly increasing previously suppressed health risks by promoting co-infections. If similar processes are present in humans, the effects of enteric virus infections might have longer-term impacts extending beyond the directly observed symptoms.",,"['Wasimuddin', 'Brändel, Stefan Dominik', 'Tschapka, Marco', 'Page, Rachel', 'Rasche, Andrea', 'Corman, Victor M.', 'Drosten, Christian', 'Sommer, Simone']",,,,
,PMC,Orally Efficacious Broad-Spectrum Ribonucleoside Analog Inhibitor of Influenza and Respiratory Syncytial Viruses,http://dx.doi.org/10.1128/AAC.00766-18,PMC6105843,,,"Morbidity and mortality resulting from influenza-like disease are a threat, especially for older adults. To improve case management, next-generation broad-spectrum antiviral therapeutics that are efficacious against major drivers of influenza-like disease, including influenza viruses and respiratory syncytial virus (RSV), are urgently needed. Using a dual-pathogen high-throughput screening protocol for influenza A virus (IAV) and RSV inhibitors, we have identified N(4)-hydroxycytidine (NHC) as a potent inhibitor of RSV, influenza B viruses, and IAVs of human, avian, and swine origins. Biochemical in vitro polymerase assays and viral RNA sequencing revealed that the ribonucleotide analog is incorporated into nascent viral RNAs in place of cytidine, increasing the frequency of viral mutagenesis. Viral passaging in cell culture in the presence of an inhibitor did not induce robust resistance. Pharmacokinetic profiling demonstrated dose-dependent oral bioavailability of 36 to 56%, sustained levels of the active 5′-triphosphate anabolite in primary human airway cells and mouse lung tissue, and good tolerability after extended dosing at 800 mg/kg of body weight/day. The compound was orally efficacious against RSV and both seasonal and highly pathogenic avian IAVs in mouse models, reducing lung virus loads and alleviating disease biomarkers. Oral dosing reduced IAV burdens in a guinea pig transmission model and suppressed virus spread to uninfected contact animals through direct transmission. Based on its broad-spectrum efficacy and pharmacokinetic properties, NHC is a promising candidate for future clinical development as a treatment option for influenza-like diseases.",,"['Yoon, Jeong-Joong', 'Toots, Mart', 'Lee, Sujin', 'Lee, Myung-Eun', 'Ludeke, Barbara', 'Luczo, Jasmina M.', 'Ganti, Ketaki', 'Cox, Robert M.', 'Sticher, Zachary M.', 'Edpuganti, Vindya', 'Mitchell, Deborah G.', 'Lockwood, Mark A.', 'Kolykhalov, Alexander A.', 'Greninger, Alexander L.', 'Moore, Martin L.', 'Painter, George R.', 'Lowen, Anice C.', 'Tompkins, Stephen M.', 'Fearns, Rachel', 'Natchus, Michael G.', 'Plemper, Richard K.']",,,,
,PMC,"Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts",http://dx.doi.org/10.1021/acs.chemrev.7b00678,PMC6763210,,,"Intracellular delivery is a key step in biological research and has enabled decades of biomedical discoveries. It is also becoming increasingly important in industrial and medical applications ranging from biomanufacture to cell-based therapies. Here, we review techniques for membrane disruption-based intracellular delivery from 1911 until the present. These methods are important because they achieves rapid, direct, and universal delivery of almost any molecule that can be dispersed in solution. We start by covering the motivations for intracellular delivery and the challenges associated with the different cargo types – nucleic acids, proteins/peptides, small molecules, synthetic nanomaterials, and large cargo. The review then presents a broad comparison of delivery strategies followed by an analysis of membrane disruption mechanisms and the biology of the cell response. We cover mechanical, electrical, thermal, optical, and chemical strategies of membrane disruption with a particular emphasis on the applications, challenges, and mechanisms of action. We hope the concepts discussed in our review inspire scientists and engineers with further ideas on how to improve intracellular delivery.",,"['Stewart, Martin P.', 'Langer, Robert', 'Jensen, Klavs F.']",,,,
,PMC,Comparison of the Xpert Flu/RSV XC and Xpress Flu/RSV Assays,http://dx.doi.org/10.1128/JCM.00278-18,PMC6062788,,,"Molecular diagnostics for influenza and respiratory syncytial virus (RSV) have become commonplace, and various tests and systems have been cleared by the FDA for use in the United States. We performed a retrospective study to compare the Cepheid Xpress Flu/RSV assay with the Xpert Flu/RSV XC assay, using laboratory-developed tests (LDTs) as the reference method. The Xpress assay was 100% accurate compared to LDTs, whereas the Xpert Flu/RSV XC assay was 96.0% accurate. The Xpress test was determined to be faster and more sensitive than the XC assay.",,"['Popowitch, Elena B.', 'Miller, Melissa B.']",,,,
,PMC,Human Polyclonal Antibodies Produced by Transchromosomal Cattle Provide Partial Protection Against Lethal Zaire Ebolavirus Challenge in Rhesus Macaques,http://dx.doi.org/10.1093/infdis/jiy430,PMC6249563,,,"Antibody therapy has been used to treat a variety of diseases and the success of ZMapp and other monoclonal antibody-based therapies during the 2014–2016 West African Ebola outbreak has shown this countermeasure can be a successful therapy for Ebola hemorrhagic fever. This study utilized transchromosomal bovines (TcB) vaccinated with a DNA plasmid encoding Ebola virus glycoprotein sequence to produce human polyclonal antibodies directed against Ebola virus glycoprotein. When administered 1 day postinfection, these TcB polyclonal antibodies provided partial protection and resulted in a 50% survival rate following a lethal challenge of Ebola virus Makona in rhesus macaques.",,"['Rosenke, Kyle', 'Bounds, Callie E', 'Hanley, Patrick W', 'Saturday, Greg', 'Sullivan, Eddie', 'Wu, Hua', 'Jiao, Jin-an', 'Feldmann, Heinz', 'Schmaljohn, Connie', 'Safronetz, David']",,,,
,PMC,Viral journeys on the intracellular highways,http://dx.doi.org/10.1007/s00018-018-2882-0,PMC6151136,,,"Viruses are obligate intracellular pathogens that are dependent on cellular machineries for their replication. Recent technological breakthroughs have facilitated reliable identification of host factors required for viral infections and better characterization of the virus-host interplay. While these studies have revealed cellular machineries that are uniquely required by individual viruses, accumulating data also indicate the presence of broadly required mechanisms. Among these overlapping cellular functions are components of intracellular membrane trafficking pathways. Here, we review recent discoveries focused on how viruses exploit intracellular membrane trafficking pathways to promote various stages of their life cycle, with an emphasis on cellular factors that are usurped by a broad range of viruses. We describe broadly required components of the endocytic and secretory pathways, the Endosomal Sorting Complexes Required for Transport (ESCRT) pathway, and the autophagy pathway. Identification of such overlapping host functions offers new opportunities to develop broad-spectrum host-targeted antiviral strategies.",,"['Robinson, Makeda', 'Schor, Stanford', 'Barouch-Bentov, Rina', 'Einav, Shirk']",,,,
,PMC,N-terminal acetylation by NatB is required for the shutoff activity of influenza A virus PA-X,http://dx.doi.org/10.1016/j.celrep.2018.06.078,PMC6296758,,,"N-terminal acetylation is a major posttranslational modification in eukaryotes catalyzed by N-terminal acetyltransferases (NATs), NatA through NatF. Although N-terminal acetylation modulates diverse protein functions, little is known about its roles in virus replication. We found that NatB, which comprises NAA20 and NAA25, is involved in the shutoff activity of influenza virus PA-X. The shutoff activity of PA-X was suppressed in NatB-deficient cells, and PA-X mutants that are not acetylated by NatB showed reduced shutoff activities. We also evaluated the importance of N-terminal acetylation of PA, because PA-X shares its N-terminal sequence with PA. Viral polymerase activity was reduced in NatB-deficient cells. Moreover, mutant PAs that are not acetylated by NatB lost their function in the viral polymerase complex. Taken together, our findings demonstrate that N-terminal acetylation is required for the shutoff activity of PA-X and for viral polymerase activity.",,"['Oishi, Kohei', 'Yamayoshi, Seiya', 'Kozuka-Hata, Hiroko', 'Oyama, Masaaki', 'Kawaoka, Yoshihiro']",,,,
,PMC,Evaluation of the effects of flushing feed manufacturing equipment with chemically treated rice hulls on porcine epidemic diarrhea virus cross-contamination during feed manufacturing,http://dx.doi.org/10.1093/jas/sky295,PMC6162582,,,"Various strategies have been proposed to mitigate potential risk of porcine epidemic diarrhea virus (PEDV) transmission via feed and feed ingredients. Wet disinfection has been found to be the most effective decontamination of feed mill surfaces; however, this is not practical on a commercial feed production scale. Another potential mitigation strategy would be using chemically treated rice hulls flushed through the feed manufacturing equipment. Therefore, the objective of this study was to determine the effects of medium-chain fatty acids (MCFA) or formaldehyde-treated rice hull flush batches as potential chemical mitigation strategies for PEDV during feed manufacturing. Feed without evidence of PEDV RNA contamination was inoculated with PEDV. Based on polymerase chain reaction analysis, this feed had a cycle threshold (Ct) = 30.2 and was confirmed infective in bioassay. After manufacturing the PEDV-positive feed, untreated rice hulls, formaldehyde-treated rice hulls, 2% MCFA- (a 1:1:1 blend of hexanoic, octanoic, and decanoic acid) treated rice hulls, or 10% MCFA-treated rice hulls were flushed through laboratory scale mixers. For the untreated rice hulls, 3 of 6 samples had detectable PEDV RNA, whereas 1 of 6 formaldehyde-treated rice hull flush samples and 2 of 6 of the 2% MCFA rice hull flush samples had detectable PEDV RNA. However, PEDV RNA was not detected in any of the 10% MCFA rice hull flush samples. Then, rice hulls treated with 10% MCFA were mixed and discharged through a production scale mixer and bucket elevator following PEDV-positive feed. No rice hull flush or feed samples from the mixer following chemically treated rice hull flush had detectible PEDV RNA. However, one 10% MCFA rice hull sample collected from the bucket elevator discharge spout had detectible PEDV RNA. Dust collected following mixing of PEDV contaminated feed had detectable PEDV RNA (Ct = 29.4) and was infectious. However, dust collected immediately after the 10% MCFA rice hull flush batch had a reduced quantity of PEDV RNA (Ct = 33.7) and did not cause infection. Overall, the use of rice hull flushes effectively reduced the quantity of detectible RNA present after mixing a batch of PEDV-positive feed. Chemical treatment of rice hulls with formaldehyde or 10% MCFA provided additional reduction in detectible RNA. Finally, dust collected after manufacturing PEDV-inoculated feed has the potential to serve as a vector for PEDV transmission.",,"['Gebhardt, Jordan T', 'Cochrane, Roger A', 'Woodworth, Jason C', 'Jones, Cassandra K', 'Niederwerder, Megan C', 'Muckey, Mary B', 'Stark, Charles R', 'Tokach, Mike D', 'DeRouchey, Joel M', 'Goodband, Robert D', 'Bai, Jianfa', 'Gauger, Philip C', 'Chen, Qi', 'Zhang, Jianqiang', 'Main, Rodger G', 'Dritz, Steve S']",,,,
,PMC,Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion,http://dx.doi.org/10.1080/15548627.2018.1474314,PMC6103682,,,"Macroautophagy/autophagy is a conserved transport pathway where targeted structures are sequestered by phagophores, which mature into autophagosomes, and then delivered into lysosomes for degradation. Autophagy is involved in the pathophysiology of numerous diseases and its modulation is beneficial for the outcome of numerous specific diseases. Several lysosomal inhibitors such as bafilomycin A(1) (BafA(1)), protease inhibitors and chloroquine (CQ), have been used interchangeably to block autophagy in in vitro experiments assuming that they all primarily block lysosomal degradation. Among them, only CQ and its derivate hydroxychloroquine (HCQ) are FDA-approved drugs and are thus currently the principal compounds used in clinical trials aimed to treat tumors through autophagy inhibition. However, the precise mechanism of how CQ blocks autophagy remains to be firmly demonstrated. In this study, we focus on how CQ inhibits autophagy and directly compare its effects to those of BafA(1). We show that CQ mainly inhibits autophagy by impairing autophagosome fusion with lysosomes rather than by affecting the acidity and/or degradative activity of this organelle. Furthermore, CQ induces an autophagy-independent severe disorganization of the Golgi and endo-lysosomal systems, which might contribute to the fusion impairment. Strikingly, HCQ-treated mice also show a Golgi disorganization in kidney and intestinal tissues. Altogether, our data reveal that CQ and HCQ are not bona fide surrogates for other types of late stage lysosomal inhibitors for in vivo experiments. Moreover, the multiple cellular alterations caused by CQ and HCQ call for caution when interpreting results obtained by blocking autophagy with this drug.",,"['Mauthe, Mario', 'Orhon, Idil', 'Rocchi, Cecilia', 'Zhou, Xingdong', 'Luhr, Morten', 'Hijlkema, Kerst-Jan', 'Coppes, Robert P.', 'Engedal, Nikolai', 'Mari, Muriel', 'Reggiori, Fulvio']",,,,
,PMC,Advancing global health and strengthening the HIV response in the era of the Sustainable Development Goals: the International AIDS Society—Lancet Commission,http://dx.doi.org/10.1016/S0140-6736(18)31070-5,PMC6323648,,,,,"['Bekker, Linda-Gail', 'Alleyne, George', 'Baral, Stefan', 'Cepeda, Javier', 'Daskalakis, Demetre', 'Dowdy, David', 'Dybul, Mark', 'Eholie, Serge', 'Esom, Kene', 'Garnett, Geoff', 'Grimsrud, Anna', 'Hakim, James', 'Havlir, Diane', 'Isbell, Michael T', 'Johnson, Leigh', 'Kamarulzaman, Adeeba', 'Kasaie, Parastu', 'Kazatchkine, Michel', 'Kilonzo, Nduku', 'Klag, Michael', 'Klein, Marina', 'Lewin, Sharon R', 'Luo, Chewe', 'Makofane, Keletso', 'Martin, Natasha K', 'Mayer, Kenneth', 'Millett, Gregorio', 'Ntusi, Ntobeko', 'Pace, Loyce', 'Pike, Carey', 'Piot, Peter', 'Pozniak, Anton', 'Quinn, Thomas C', 'Rockstroh, Jurgen', 'Ratevosian, Jirair', 'Ryan, Owen', 'Sippel, Serra', 'Spire, Bruno', 'Soucat, Agnes', 'Starrs, Ann', 'Strathdee, Steffanie A', 'Thomson, Nicholas', 'Vella, Stefano', 'Schechter, Mauro', 'Vickerman, Peter', 'Weir, Brian', 'Beyrer, Chris']",,,,
,PMC,Lipid Structure and Composition Control Consequences of Interleaflet Coupling in Asymmetric Vesicles,http://dx.doi.org/10.1016/j.bpj.2018.07.011,PMC6103735,,,"Using Förster resonance energy transfer, raft/liquid-ordered-domain formation was assessed in asymmetric vesicles containing outer leaflets composed of high-Tm (melting temperature) saturated phosphatidylcholines (diC(18:0)PC, diC(16:0)PC, diC(15:0)PC, or diC(14:0)PC), low-Tm unsaturated dioleoylphosphatidylcholine (DOPC) and cholesterol, and inner leaflets composed of lipids that by themselves would not form ordered domains (DOPC and cholesterol). Ordered-domain formation in the outer leaflet was compared to that in symmetric vesicles with the same lipid composition as the asymmetric vesicle outer leaflets. The difference between ordered-domain thermal stability in asymmetric and symmetric vesicles was highly dependent on high-Tm PC acyl-chain length. At one extreme, in diC(14:0)PC-containing asymmetric vesicles, the outer leaflet did not segregate to form ordered domains over the entire experimental temperature range even though ordered domains formed in the symmetric vesicles, indicating the inner leaflet dominated outer-leaflet physical behavior in the asymmetric vesicles. At the other extreme, in diC(18:0)PC-containing asymmetric vesicles, ordered domains formed over the entire temperature range at which they were present in symmetric vesicles, indicating the inner leaflet did not dominate outer-leaflet physical behavior. DiC(15:0)PC- and diC(16:0)PC-containing vesicles exhibited intermediate behaviors. A different set of vesicles was prepared with high-Tm lipid sphingomyelin (SM) in place of saturated phosphatidylcholine, and the % SM was varied. The thermal stability of outer-leaflet ordered domains in asymmetric vesicles was found to decrease more than in symmetric vesicles as SM levels decreased, indicating that the inner leaflet increasingly dominated outer leaflet physical state as SM levels decreased. Overall, inhibition of outer-leaflet ordered-domain formation in asymmetric vesicles by inner-leaflet lipids decreased as the ability of outer-leaflet lipids to form an ordered state by themselves increased, i.e., when outer-leaflet high-Tm lipid content or acyl-chain length increased. This has implications for how ordered-domain formation may be controlled in vivo.",,"['Wang, Qing', 'London, Erwin']",,,,
,PMC,Gene Birth Contributes to Structural Disorder Encoded by Overlapping Genes,http://dx.doi.org/10.1534/genetics.118.301249,PMC6116962,,,"The same nucleotide sequence can encode two protein products in different reading frames. Overlapping gene regions encode higher levels of intrinsic structural disorder (ISD) than nonoverlapping genes (39% vs. 25% in our viral dataset). This might be because of the intrinsic properties of the genetic code, because one member per pair was recently born de novo in a process that favors high ISD, or because high ISD relieves increased evolutionary constraint imposed by dual-coding. Here, we quantify the relative contributions of these three alternative hypotheses. We estimate that the recency of de novo gene birth explains [Formula: see text] or more of the elevation in ISD in overlapping regions of viral genes. While the two reading frames within a same-strand overlapping gene pair have markedly different ISD tendencies that must be controlled for, their effects cancel out to make no net contribution to ISD. The remaining elevation of ISD in the older members of overlapping gene pairs, presumed due to the need to alleviate evolutionary constraint, was already present prior to the origin of the overlap. Same-strand overlapping gene birth events can occur in two different frames, favoring high ISD either in the ancestral gene or in the novel gene; surprisingly, most de novo gene birth events contained completely within the body of an ancestral gene favor high ISD in the ancestral gene (23 phylogenetically independent events vs. 1). This can be explained by mutation bias favoring the frame with more start codons and fewer stop codons.",,"['Willis, Sara', 'Masel, Joanna']",,,,
,PMC,Cytokines and CD8 T cell immunity during respiratory syncytial virus infection,http://dx.doi.org/10.1016/j.cyto.2018.07.012,PMC6551303,,,"Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection and hospitalization in infants. In spite of the enormous clinical burden caused by RSV infections, there remains no efficacious RSV vaccine. CD8 T cells mediate viral clearance as well as provide protection against a secondary RSV infection. However, RSV-specific CD8 T cells may also induce immunopathology leading to exacerbated morbidity and mortality. Many of the crucial functions performed by CD8 T cells are mediated by the cytokines they produce. IFN-γ and TNF are produced by CD8 T cells following RSV infection and contribute to both the acceleration of viral clearance and the induction of immunopathology. To prevent immunopathology, regulatory mechanisms are in place within the immune system to inhibit CD8 T cell effector functions after the infection has been cleared. The actions of a variety of cytokines, including IL-10 and IL-4, play a critical role in the regulation of CD8 T cell effector activity. Herein, we review the current literature on CD8 T cell responses and the functions of the cytokines they produce following RSV infection. Additionally, we discuss the regulation of CD8 T cell activation and effector functions through the actions of various cytokines.",,"['Schmidt, Megan E.', 'Varga, Steven M.']",,,,
,PMC,A Processive Protein Chimera Introduces Mutations Across Defined DNA Regions In Vivo,http://dx.doi.org/10.1021/jacs.8b04001,PMC6166643,,,"Laboratory time scale evolution in vivo relies on the generation of large, mutationally diverse gene libraries to rapidly explore biomolecule sequence landscapes. Traditional global mutagenesis methods are problematic because they introduce many off-target mutations that are often lethal and can engender false positives. We report the development and application of the MutaT7 chimera, a potent and highly targeted in vivo mutagenesis agent. MutaT7 utilizes a DNA-damaging cytidine deaminase fused to a processive RNA polymerase to continuously direct mutations to specific, well-defined DNA regions of any relevant length. MutaT7 thus provides a mechanism for in vivo targeted mutagenesis across multi-kb DNA sequences. MutaT7 should prove useful in diverse organisms, opening the door to new types of in vivo evolution experiments.",,"['Moore, Christopher L.', 'Papa, Louis J.', 'Shoulders, Matthew D.']",,,,
,PMC,Optimal treatment allocations in space and time for on-line control of an emerging infectious disease,,PMC6334759,,,"A key component in controlling the spread of an epidemic is deciding where, when and to whom to apply an intervention. We develop a framework for using data to inform these decisions in realtime. We formalize a treatment allocation strategy as a sequence of functions, one per treatment period, that map up-to-date information on the spread of an infectious disease to a subset of locations where treatment should be allocated. An optimal allocation strategy optimizes some cumulative outcome, e.g. the number of uninfected locations, the geographic footprint of the disease or the cost of the epidemic. Estimation of an optimal allocation strategy for an emerging infectious disease is challenging because spatial proximity induces interference between locations, the number of possible allocations is exponential in the number of locations, and because disease dynamics and intervention effectiveness are unknown at out-break. We derive a Bayesian on-line estimator of the optimal allocation strategy that combines simulation–optimization with Thompson sampling. The estimator proposed performs favourably in simulation experiments. This work is motivated by and illustrated using data on the spread of white nose syndrome, which is a highly fatal infectious disease devastating bat populations in North America.",,"['Laber, Eric B.', 'Meyer, Nick J.', 'Reich, Brian J.', 'Pacifici, Krishna', 'Collazo, Jaime A.', 'Drake, John M.']",,,,
,PMC,Sialylated keratan sulfate proteoglycans are Siglec-8 ligands in human airways,http://dx.doi.org/10.1093/glycob/cwy057,PMC6142871,,,"Human siglecs are a family of 14 sialic acid-binding proteins, most of which are expressed on subsets of immune cells where they regulate immune responses. Siglec-8 is expressed selectively on human allergic inflammatory cells—primarily eosinophils and mast cells—where engagement causes eosinophil apoptosis and inhibits mast cell mediator release. Evidence supports a model in which human eosinophils and mast cells bind to Siglec-8 sialoglycan ligands on inflammatory target tissues to resolve allergic inflammation and limit tissue damage. To identify Siglec-8-binding sialoglycans from human airways, proteins extracted from postmortem human trachea were resolved by size-exclusion chromatography and composite agarose–acrylamide gel electrophoresis, blotted and probed by Siglec-8-Fc blot overlay. Three size classes of Siglec-8 ligands were identified: 250 kDa, 600 kDa and 1 MDa, each of which was purified by affinity chromatography using a recombinant pentameric form of Siglec-8. Proteomic mass spectrometry identified all size classes as the proteoglycan aggrecan, a finding validated by immunoblotting. Glycan array studies demonstrated Siglec-8 binding to synthetic glycans with a terminal Neu5Acα2-3(6-sulfo)-Gal determinant, a quantitatively minor terminus on keratan sulfate (KS) chains of aggrecan. Treating human tracheal extracts with sialidase or keratanase eliminated Siglec-8 binding, indicating sialylated KS chains as Siglec-8-binding determinants. Treating human tracheal histological sections with keratanase also completely eliminated the binding of Siglec-8-Fc. Finally, Siglec-8 ligand purified from human trachea extracts induced increased apoptosis of freshly isolated human eosinophils in vitro. We conclude that sialylated KS proteoglycans are endogenous human airway ligands that bind Siglec-8 and may regulate allergic inflammation.",,"['Gonzalez-Gil, Anabel', 'Porell, Ryan N', 'Fernandes, Steve M', 'Wei, Yadong', 'Yu, Huifeng', 'Carroll, Daniela J', 'McBride, Ryan', 'Paulson, James C', 'Tiemeyer, Michael', 'Aoki, Kazuhiro', 'Bochner, Bruce S', 'Schnaar, Ronald L']",,,,
,PMC,Porcine Deltacoronavirus Accessory Protein NS6 Antagonizes Interferon Beta Production by Interfering with the Binding of RIG-I/MDA5 to Double-Stranded RNA,http://dx.doi.org/10.1128/JVI.00712-18,PMC6052322,,,"Porcine deltacoronavirus (PDCoV) has recently emerged as an enteric pathogen that can cause serious vomiting and diarrhea in suckling piglets. The first outbreak of PDCoV occurred in the United States in 2014 and was followed by reports of PDCoV in South Korea, China, Thailand, Lao People's Democratic Republic, and Vietnam, leading to economic losses for pig farms and posing a considerable threat to the swine industry worldwide. Our previous studies have shown that PDCoV encodes three accessory proteins, NS6, NS7, and NS7a, but the functions of these proteins in viral replication, pathogenesis, and immune regulation remain unclear. Here, we found that ectopic expression of accessory protein NS6 significantly inhibits Sendai virus-induced interferon beta (IFN-β) production as well as the activation of transcription factors IRF3 and NF-κB. Interestingly, NS6 does not impede the IFN-β promoter activation mediated via key molecules in the RIG-I-like receptor (RLR) signaling pathway, specifically RIG-I, MDA5, and their downstream molecules MAVS, TBK1, IKKε, and IRF3. Further analyses revealed that NS6 is not an RNA-binding protein; however, it interacts with RIG-I/MDA5. This interaction attenuates the binding of double-stranded RNA by RIG-I/MDA5, resulting in the reduction of RLR-mediated IFN-β production. Taken together, our results demonstrate that ectopic expression of NS6 antagonizes IFN-β production by interfering with the binding of RIG-I/MDA5 to double-stranded RNA, revealing a new strategy employed by PDCoV accessory proteins to counteract the host innate antiviral immune response. IMPORTANCE Coronavirus accessory proteins are species specific, and they perform multiple functions in viral pathogenicity and immunity, such as acting as IFN antagonists and cell death inducers. Our previous studies have shown that PDCoV encodes three accessory proteins. Here, we demonstrated for the first time that PDCoV accessory protein NS6 antagonizes IFN-β production by interacting with RIG-I and MDA5 to impede their association with double-stranded RNA. This is an efficient strategy of antagonizing type I IFN production by disrupting the binding of host pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs). These findings deepen our understanding of the function of accessory protein NS6, and they may direct us toward novel therapeutic targets and lead to the development of more effective vaccines against PDCoV infection.",,"['Fang, Puxian', 'Fang, Liurong', 'Ren, Jie', 'Hong, Yingying', 'Liu, Xiaorong', 'Zhao, Yunyang', 'Wang, Dang', 'Peng, Guiqing', 'Xiao, Shaobo']",,,,
,PMC,Discovery and Sequence Analysis of Four Deltacoronaviruses from Birds in the Middle East Reveal Interspecies Jumping with Recombination as a Potential Mechanism for Avian-to-Avian and Avian-to-Mammalian Transmission,http://dx.doi.org/10.1128/JVI.00265-18,PMC6052312,,,"The emergence of Middle East respiratory syndrome showed once again that coronaviruses (CoVs) in animals are potential source for epidemics in humans. To explore the diversity of deltacoronaviruses in animals in the Middle East, we tested fecal samples from 1,356 mammals and birds in Dubai, The United Arab Emirates. Four novel deltacoronaviruses were detected from eight birds of four species by reverse transcription-PCR (RT-PCR): FalCoV UAE-HKU27 from a falcon, HouCoV UAE-HKU28 from a houbara bustard, PiCoV UAE-HKU29 from a pigeon, and QuaCoV UAE-HKU30 from five quails. Complete genome sequencing showed that FalCoV UAE-HKU27, HouCoV UAE-HKU28, and PiCoV UAE-HKU29 belong to the same CoV species, suggesting recent interspecies transmission between falcons and their prey, houbara bustards and pigeons, possibly along the food chain. Western blotting detected specific anti-FalCoV UAE-HKU27 antibodies in 33 (75%) of 44 falcon serum samples, supporting genuine infection in falcons after virus acquisition. QuaCoV UAE-HKU30 belongs to the same CoV species as porcine coronavirus HKU15 (PorCoV HKU15) and sparrow coronavirus HKU17 (SpCoV HKU17), discovered previously from swine and tree sparrows, respectively, supporting avian-to-swine transmission. Recombination involving the spike protein is common among deltacoronaviruses, which may facilitate cross-species transmission. FalCoV UAE-HKU27, HouCoV UAE-HKU28, and PiCoV UAE-HKU29 originated from recombination between white-eye coronavirus HKU16 (WECoV HKU16) and magpie robin coronavirus HKU18 (MRCoV HKU18), QuaCoV UAE-HKU30 from recombination between PorCoV HKU15/SpCoV HKU17 and munia coronavirus HKU13 (MunCoV HKU13), and PorCoV HKU15 from recombination between SpCoV HKU17 and bulbul coronavirus HKU11 (BuCoV HKU11). Birds in the Middle East are hosts for diverse deltacoronaviruses with potential for interspecies transmission. IMPORTANCE During an attempt to explore the diversity of deltacoronaviruses among mammals and birds in Dubai, four novel deltacoronaviruses were detected in fecal samples from eight birds of four different species: FalCoV UAE-HKU27 from a falcon, HouCoV UAE-HKU28 from a houbara bustard, PiCoV UAE-HKU29 from a pigeon, and QuaCoV UAE-HKU30 from five quails. Genome analysis revealed evidence of recent interspecies transmission between falcons and their prey, houbara bustards and pigeons, possibly along the food chain, as well as avian-to-swine transmission. Recombination, which is known to occur frequently in some coronaviruses, was also common among these deltacoronaviruses and occurred predominantly at the spike region. Such recombination, involving the receptor binding protein, may contribute to the emergence of new viruses capable of infecting new hosts. Birds in the Middle East are hosts for diverse deltacoronaviruses with potential for interspecies transmission.",,"['Lau, Susanna K. P.', 'Wong, Emily Y. M.', 'Tsang, Chi-Ching', 'Ahmed, Syed Shakeel', 'Au-Yeung, Rex K. H.', 'Yuen, Kwok-Yung', 'Wernery, Ulrich', 'Woo, Patrick C. Y.']",,,,
,PMC,Transmembrane Protein pUL50 of Human Cytomegalovirus Inhibits ISGylation by Downregulating UBE1L,http://dx.doi.org/10.1128/JVI.00462-18,PMC6052311,,,"Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that can be conjugated to proteins via an enzymatic cascade involving the E1, E2, and E3 enzymes. ISG15 expression and protein ISGylation modulate viral infection; however, the viral mechanisms regulating the function of ISG15 and ISGylation are not well understood. We recently showed that ISGylation suppresses the growth of human cytomegalovirus (HCMV) at multiple steps of the virus life cycle and that the virus-encoded pUL26 protein inhibits protein ISGylation. In this study, we demonstrate that the HCMV UL50-encoded transmembrane protein, a component of the nuclear egress complex, also inhibits ISGylation. pUL50 interacted with UBE1L, an E1-activating enzyme for ISGylation, and (to a lesser extent) with ISG15, as did pUL26. However, unlike pUL26, pUL50 caused proteasomal degradation of UBE1L. The UBE1L level induced in human fibroblast cells by interferon beta treatment or virus infection was reduced by pUL50 expression. This activity of pUL50 involved the transmembrane (TM) domain within its C-terminal region, although pUL50 could interact with UBE1L in a manner independent of the TM domain. Consistently, colocalization of pUL50 with UBE1L was observed in cells treated with a proteasome inhibitor. Furthermore, we found that RNF170, an endoplasmic reticulum (ER)-associated ubiquitin E3 ligase, interacted with pUL50 and promoted pUL50-mediated UBE1L degradation via ubiquitination. Our results demonstrate a novel role for the pUL50 transmembrane protein of HCMV in the regulation of protein ISGylation. IMPORTANCE Proteins can be conjugated covalently by ubiquitin or ubiquitin-like proteins, such as SUMO and ISG15. ISG15 is highly induced in viral infection, and ISG15 conjugation, termed ISGylation, plays important regulatory roles in viral growth. Although ISGylation has been shown to negatively affect many viruses, including human cytomegalovirus (HCMV), viral countermeasures that might modulate ISGylation are not well understood. In the present study, we show that the transmembrane protein encoded by HCMV UL50 inhibits ISGylation by causing proteasomal degradation of UBE1L, an E1-activating enzyme for ISGylation. This pUL50 activity requires membrane targeting. In support of this finding, RNF170, an ER-associated ubiquitin E3 ligase, interacts with pUL50 and promotes UL50-mediated UBE1L ubiquitination and degradation. Our results provide the first evidence, to our knowledge, that viruses can regulate ISGylation by directly targeting the ISGylation E1 enzyme.",,"['Lee, Myoung Kyu', 'Kim, Ye Ji', 'Kim, Young-Eui', 'Han, Tae-Hee', 'Milbradt, Jens', 'Marschall, Manfred', 'Ahn, Jin-Hyun']",,,,
,PMC,The PERK Arm of the Unfolded Protein Response Negatively Regulates Transmissible Gastroenteritis Virus Replication by Suppressing Protein Translation and Promoting Type I Interferon Production,http://dx.doi.org/10.1128/JVI.00431-18,PMC6052291,,,"Coronavirus replication is closely associated with the endoplasmic reticulum (ER), the primary cellular organelle for protein synthesis, folding, and modification. ER stress is a common consequence in coronavirus-infected cells. However, how the virus-induced ER stress influences coronavirus replication and pathogenesis remains controversial. Here, we demonstrated that infection with the alphacoronavirus transmissible gastroenteritis virus (TGEV) induced ER stress and triggered the unfolded protein response (UPR) in vitro and in vivo, and ER stress negatively regulated TGEV replication in vitro. Although TGEV infection activated all three UPR pathways (activating transcription factor 6 [ATF6], inositol-requiring enzyme 1 [IRE1], and protein kinase R-like ER kinase [PERK]), the virus-triggered UPR suppressed TGEV replication in both swine testicular (ST) and IPEC-J2 cells primarily through activation of the PERK-eukaryotic initiation factor 2α (eIF2α) axis, as shown by functional studies with overexpression, small interfering RNA (siRNA), or specific chemical inhibitors. Moreover, we demonstrated that PERK-eIF2α axis-mediated inhibition of TGEV replication occurs through phosphorylated eIF2α-induced overall attenuation of protein translation. In addition to direct inhibition of viral production, the PERK-eIF2α pathway activated NF-κB and then facilitated type I IFN production, resulting in TGEV suppression. Taken together, our results suggest that the TGEV-triggered PERK-eIF2α pathway negatively regulates TGEV replication and represents a vital aspect of host innate responses to invading pathogens. IMPORTANCE The induction of ER stress is a common outcome in cells infected with coronaviruses. The UPR initiated by ER stress is actively involved in viral replication and modulates the host innate responses to the invading viruses, but these underlying mechanisms remain incompletely understood. We show here that infection with the alphacoronavirus TGEV elicited ER stress in vitro and in vivo, and the UPR PERK-eIF2α branch was predominantly responsible for the suppression of TGEV replication by ER stress. Furthermore, the PERK-eIF2α axis inhibited TGEV replication through direct inhibition of viral proteins due to global translation inhibition and type I IFN induction. These findings highlight a critical role of the UPR PERK-eIF2α pathway in modulating host innate immunity and coronavirus replication.",,"['Xue, Mei', 'Fu, Fang', 'Ma, Yanlong', 'Zhang, Xin', 'Li, Liang', 'Feng, Li', 'Liu, Pinghuang']",,,,
,PMC,Development and validation of a real-time PCR for the detection and quantification of porcine circovirus type 2,http://dx.doi.org/10.1007/s13337-018-0476-y,PMC6111954,,,"Porcine circovirus type 2 (PCV2) is a spherical and non-enveloped virus belonging to the genus Circovirus of the Circoviridae family with a single stranded circular DNA genome. This virus, already detected worldwide, has been associated to several diseases and was implicated as the etiological agent of a disease named postweaning multisystemic wasting syndrome. Several methods have been described for the detection of PCV2, being real-time PCR the most simple and reliable. As far as we know, all the real-time PCR systems described until now are based on ORF2 gene, that exhibit the highest variability. This paper reports the development and validation of a real-time PCR targeted to ORF1 and based on a TaqMan probe for the detection of porcine circovirus type 2 DNA in swine samples. Due to the lack of PCV1 samples, the ability of the test to discriminate between PCV1 and PCV2 positive samples was evaluated in silico. Estimations of 100% specificity and 100% sensitivity were obtained based on the qPCR results with panel of 81 swine samples (known PCV2-positive (n = 50); known PCV2-negative (n = 17); samples positive to other common swine viral pathogens (n = 13) and one sample from a BFDV-positive parrot (n = 1)). Intra- and inter-assay coefficients of variation obtained with three positive samples of different viral charges in five replicates or in five independent assays were below the acceptance threshold. The limit of detection determined with a recombinant plasmid containing the amplicon, led to conclude that this assay can detect at least three plasmid copies.",,"['Henriques, Ana Margarida', 'Duarte, Margarida', 'Barros, Sílvia Carla', 'Fagulha, Teresa', 'Ramos, Fernanda', 'Luís, Tiago', 'Fevereiro, Miguel']",,,,
,PMC,Passive immunization with influenza haemagglutinin specific monoclonal antibodies,http://dx.doi.org/10.1080/21645515.2018.1489947,PMC6314409,,,"The isolation of broadly neutralising antibodies against the influenza haemagglutinin has spurred investigation into their clinical potential, and has led to advances in influenza virus biology and universal influenza vaccine development. Studies in animal models have been invaluable for demonstrating the prophylactic and therapeutic efficacy of broadly neutralising antibodies, for comparisons with antiviral drugs used as the standard of care, and for defining their mechanism of action and potential role in providing protection from airborne infection.",,"['Rudraraju, Rajeev', 'Subbarao, Kanta']",,,,
,PMC,Suppression of Staphylococcus aureus virulence by a small-molecule compound,http://dx.doi.org/10.1073/pnas.1720520115,PMC6077739,,,"Emerging antibiotic resistance among bacterial pathogens has necessitated the development of alternative approaches to combat drug-resistance-associated infection. The abolition of Staphylococcus aureus virulence by targeting multiple-virulence gene products represents a promising strategy for exploration. A multiplex promoter reporter platform using gfp-luxABCDE dual-reporter plasmids with selected promoters from S. aureus-virulence-associated genes was used to identify compounds that modulate the expression of virulence factors. One small-molecule compound, M21, was identified from a chemical library to reverse virulent S. aureus into its nonvirulent state. M21 is a noncompetitive inhibitor of ClpP and alters α-toxin expression in a ClpP-dependent manner. A mouse model of infection indicated that M21 could attenuate S. aureus virulence. This nonantibiotic compound has been shown to suppress the expression of multiple unrelated virulence factors in S. aureus, suggesting that targeting a master regulator of virulence is an effective way to control virulence. Our results illustrate the power of chemical genetics in the modulation of virulence gene expression in pathogenic bacteria.",,"['Gao, Peng', 'Ho, Pak Leung', 'Yan, Bingpeng', 'Sze, Kong Hung', 'Davies, Julian', 'Kao, Richard Yi Tsun']",,,,
,PMC,Adaptation by copy number variation in monopartite viruses,http://dx.doi.org/10.1016/j.coviro.2018.07.001,PMC6289852,,,"Viruses evolve rapidly in response to host defenses and to exploit new niches. Gene amplification, a common adaptive mechanism in prokaryotes, archaea, and eukaryotes, has also contributed to viral evolution, especially of large DNA viruses. In experimental systems, gene amplification is one mechanism for rapidly overcoming selective pressures. Because the amplification generally incurs a fitness cost, emergence of adaptive point mutations within the amplified locus or elsewhere in the genome can enable collapse of the locus back to a single copy. Evidence of gene amplification followed by subfunctionalization or neofunctionalization of the copies is apparent by the presence of families of paralogous genes in many DNA viruses. These observations suggest that copy number variation has contributed broadly to virus evolution.",,"['Bayer, Avraham', 'Brennan, Greg', 'Geballe, Adam P.']",,,,
,PMC,Fresh approaches to vaccine development: New financial and economic models are required to bring more vaccines against a wider range of diseases to the market,http://dx.doi.org/10.15252/embr.201846675,PMC6073068,,,"Many promising vaccine candidates have not made it to the market, owing to economic rather than scientific factors. Market incentives, shared responsibility, and novel technologies could spur innovation to develop vaccines against a wider range of diseases. [Image: see text]",,"Gristwood, Adam",,,,
,PMC,Temporal requirement for pulmonary resident and circulating T cells during virulent Francisella tularensis infection,http://dx.doi.org/10.4049/jimmunol.1800052,PMC6086594,,,"The lung is a complex organ with anatomically distinct pools of T cells that play specific roles in combating infection. Our knowledge regarding the generation and/or maintenance of immunity by parenchymal or circulating T cells has been gathered from either persistent (>60 days) or rapidly cleared (<10 days) infections. However, the roles of these distinct T cell pools in infections that are cleared over the course of several weeks are not understood. Clearance of the highly virulent intracellular bacterium, Francisella tularensis (Ftt) following pulmonary infection of immune animals is a protracted, T cell dependent process requiring approximately 30-40 days and serves as a model for infections that are not acutely controlled. Using this model, we found that intranasal vaccination increased the number of tissue resident CD4(+) T(eff) cells and subsequent challenge of immune mice with Ftt led to a significant expansion of polyfunctional, parenchymal CD4(+) T(eff) cells compared to the circulating pool. Despite the dominant in vivo response by parenchymal CD4(+) T cells after vaccination and challenge, circulating CD4(+) T cells were superior at controlling intracellular Ftt replication in vitro. Further examination in vivo revealed temporal requirements for resident and circulating T cells during Ftt infection. These requirements were in direct contrast to other pulmonary infections that are cleared rapidly in immune animals. The data herein provide important insights into the role of specific T cell populations that will be essential for design of novel effective vaccines against tularemia and potentially other agents of pulmonary infection.",,"['Roberts, Lydia M', 'Wehrly, Tara D', 'Ireland, Robin M', 'Crane, Deborah D', 'Scott, Dana P', 'Bosio, Catharine M']",,,,
,PMC,Principles for targeting RNA with drug-like small molecules,http://dx.doi.org/10.1038/nrd.2018.93,PMC6420209,,,"RNA molecules are essential for cellular information transfer and gene regulation, and RNAs have been implicated in many human diseases. Messenger and non-coding RNAs contain highly structured elements, and evidence suggests that many of these structures are important for function. Targeting these RNAs with small molecules offers opportunities to therapeutically modulate numerous cellular processes, including those linked to “undruggable” protein targets. Despite this promise, there is currently only a single class of human-designed small molecules that target RNA used clinically – the linezolid antibiotics. A growing number of small-molecule RNA ligands are being identified, however, leading to burgeoning interest in the field. Here, we discuss principles for discovering small-molecule drugs that target RNA and argue that the overarching challenge is to identify appropriate target structures – namely in disease-causing RNAs that have high information content, and consequently appropriate ligand binding pockets. If focus is placed on such druggable binding sites in RNA, extensive knowledge of the kinds of molecules that comprise conventional drugs could then enable small-molecule drug discovery for RNA targets to become (only) roughly as difficult as for protein targets.",,"['Warner, Katherine Deigan', 'Hajdin, Christine E.', 'Weeks, Kevin M.']",,,,
,PMC,Virological and Immunological Outcomes of Coinfections,http://dx.doi.org/10.1128/CMR.00111-17,PMC6148187,,,"Coinfections involving viruses are being recognized to influence the disease pattern that occurs relative to that with single infection. Classically, we usually think of a clinical syndrome as the consequence of infection by a single virus that is isolated from clinical specimens. However, this biased laboratory approach omits detection of additional agents that could be contributing to the clinical outcome, including novel agents not usually considered pathogens. The presence of an additional agent may also interfere with the targeted isolation of a known virus. Viral interference, a phenomenon where one virus competitively suppresses replication of other coinfecting viruses, is the most common outcome of viral coinfections. In addition, coinfections can modulate virus virulence and cell death, thereby altering disease severity and epidemiology. Immunity to primary virus infection can also modulate immune responses to subsequent secondary infections. In this review, various virological mechanisms that determine viral persistence/exclusion during coinfections are discussed, and insights into the isolation/detection of multiple viruses are provided. We also discuss features of heterologous infections that impact the pattern of immune responsiveness that develops.",,"['Kumar, Naveen', 'Sharma, Shalini', 'Barua, Sanjay', 'Tripathi, Bhupendra N.', 'Rouse, Barry T.']",,,,
,PMC,TMPRSS11A activates the influenza A virus hemagglutinin and the MERS coronavirus spike protein and is insensitive against blockade by HAI-1,http://dx.doi.org/10.1074/jbc.RA118.001273,PMC6130959,,,"The influenza virus hemagglutinin (HA) facilitates viral entry into target cells. Cleavage of HA by host cell proteases is essential for viral infectivity, and the responsible enzymes are potential targets for antiviral intervention. The type II transmembrane serine protease (TTSP) TMPRSS2 has been identified as an HA activator in cell culture and in the infected host. However, it is less clear whether TMPRSS2-related enzymes can also activate HA for spread in target cells. Moreover, the activity of cellular serine protease inhibitors against HA-activating TTSPs is poorly understood. Here, we show that TMPRSS11A, another member of the TTSP family, cleaves and activates the influenza A virus (FLUAV) HA and the Middle East respiratory syndrome coronavirus spike protein (MERS-S). Moreover, we demonstrate that TMPRSS11A is expressed in murine tracheal epithelium, which is a target of FLUAV infection, and in human trachea, suggesting that the protease could support FLUAV spread in patients. Finally, we show that HA activation by the TMPRSS11A-related enzymes human airway tryptase and DESC1, but not TMPRSS11A itself, is blocked by the cellular serine protease inhibitor hepatocyte growth factor activator inhibitor type-1 (HAI-1). Our results suggest that TMPRSS11A could promote FLUAV spread in target cells and that HA-activating TTSPs exhibit differential sensitivity to blockade by cellular serine protease inhibitors.",,"['Zmora, Pawel', 'Hoffmann, Markus', 'Kollmus, Heike', 'Moldenhauer, Anna-Sophie', 'Danov, Olga', 'Braun, Armin', 'Winkler, Michael', 'Schughart, Klaus', 'Pöhlmann, Stefan']",,,,
,PMC,Legacy and Social Media Respectively Influence Risk Perceptions and Protective Behaviors During Emerging Health Threats: A Multi-Wave Analysis of Communications on Zika Virus Cases,http://dx.doi.org/10.1016/j.socscimed.2018.07.007,PMC6093206,,,"OBJECTIVE: Both legacy media, such as television and newspapers, and online social media are potentially important but incompletely understood sources of information in the face of emerging public health risks. This research aimed to understand media effects on risk perceptions and behaviors concerning the Zika virus in the United States. METHODS: We analyzed a multi-wave nationally representative survey (N = 29,062) and the volume of communications in social and legacy media (i.e., legacy media data from news sources and databases, N = 2,660 and social media data from Twitter, N = 1,605,752) in the United States between April and October 2016, dates coinciding with the early cases of local transmission of Zika in the United States (i.e., 25 weeks). The present study conducted econometric analyses (i.e., Granger causality tests) to assess the associations of legacy and social media coverage with risk perceptions and protective behaviors in the total sample and specific groups separated by pregnancy status/intent, geographic region, income, education level, age, and ethnicity. RESULTS: The results from the overall sample suggested that changes in the volume of information in legacy and social media (i.e., Twitter) were followed by different changes in community risk perceptions and protective behaviors. Specifically, social media coverage correlated with the level of risk perceptions, whereas the legacy media coverage correlated with the level of protective behaviors. Analyses across different subpopulations, including those of different pregnancy status/intent, geographic Zika risk, income, education level, age, and ethnicity, replicated the social media associations with risk perceptions in most cases. However, legacy media and protective behaviors were linked only in some vulnerable subpopulations (e.g., the less-educated populations). CONCLUSION: Understanding how media coverage relates to Zika risk perceptions and protective behaviors will help to facilitate effective risk communications by healthcare professionals and providers, particularly when a health risk emerges.",,"['Chan, Man-pui Sally', 'Winneg, Kenneth', 'Hawkins, Lauren', 'Farhadloo, Mohsen', 'Jamieson, Kathleen Hall', 'Albarracín, Dolores']",,,,
,PMC,Repurposing Potential of 1(st) Generation H(1)-specific Antihistamines as Anti-filovirus Therapeutics,http://dx.doi.org/10.1016/j.antiviral.2018.07.003,PMC6087678,,,"Ebola and Marburg are filoviruses and biosafety level 4 pathogens responsible for causing severe hemorrhagic fevers in humans with mortality rates up to 90%. The most recent outbreak in West Africa resulted in approximately 11,310 deaths in 28,616 reported cases. Currently there are no FDA-approved vaccines or therapeutics to treat infections of these deadly viruses. Recently we screened an FDA-approved drug library and identified numerous G protein-coupled receptor (GPCR) antagonists including antihistamines possessing anti-filovirus properties. Antihistamines are attractive targets for drug repurposing because of their low cost and ease of access due to wide use. In this report we identify common over the counter antihistamines, such as diphenhydramine (Benadryl) and chlorcyclizine (Ahist) as potential candidates for repurposing as anti-filovirus agents. Furthermore, we demonstrate that this potential is wide-spread through the 1(st) generation of H(1)-specific antihistamines but is not present in newer drugs or drugs targeting H(2), H(3) and H(4) receptors. We showed that the filovirus entry inhibition is not dependent on the classical antagonism of cell surface histamine or muscarinic acetylcholine receptors but occurs in the endosome, like the cathepsin inhibitor CA-074. Finally, using extensive docking studies we showed the potential for these drugs to bind directly to the EBOV-GP at the same site as toremifene. These findings suggest that the 1(st) generation antihistamines are excellent candidates for repurposing as anti-filovirus therapeutics and can be further optimized for removal of unwanted histamine or muscarinic receptor interactions without loss of anti-filovirus efficacy.",,"['Schafer, Adam', 'Cheng, Han', 'Xiong, Rui', 'Soloveva, Veronica', 'Retterer, Cary', 'Mo, Feiyan', 'Bavari, Sina', 'Thatcher, Gregory', 'Rong, Lijun']",,,,
,PMC,Quantifying TB transmission: a systematic review of reproduction number and serial interval estimates for tuberculosis,http://dx.doi.org/10.1017/S0950268818001760,PMC6092233,,,"Tuberculosis (TB) is the leading global infectious cause of death. Understanding TB transmission is critical to creating policies and monitoring the disease with the end goal of TB elimination. To our knowledge, there has been no systematic review of key transmission parameters for TB. We carried out a systematic review of the published literature to identify studies estimating either of the two key TB transmission parameters: the serial interval and the reproductive number. We identified five publications that estimated the serial interval and 56 publications that estimated the reproductive number. The serial interval estimates from four studies were: 0.57, 1.42, 1.44 and 1.65 years; the fifth paper presented age-specific estimates ranging from 20-30 years (for infants <1 year old) to less than five years (for adults). The reproductive number estimates ranged from 0.24 in the Netherlands (during 1933-2007) to 4.3 in China in 2012. We found a limited number of publications and many high TB burden settings were not represented. Certain features of TB dynamics, such as slow transmission, complicated parameter estimation, require novel methods. Additional efforts to estimate these parameters for TB are needed so that we can monitor and evaluate interventions designed to achieve TB elimination.",,"['Ma, Y.', 'Horsburgh, C. R.', 'White, L. F.', 'Jenkins, H. E.']",,,,
,PMC,"Samantha Adams Festschrift: Adamsian Discourse—The Patient, and Everything Else",http://dx.doi.org/10.1055/s-0038-1654701,PMC6029926,,,,,"['DeMuro, Paul R.', 'Novak, Laurie L.', 'Petersen, Carolyn']",,,,
,PMC,A large-scale location-based social network to understanding the impact of human geo-social interaction patterns on vaccination strategies in an urbanized area,http://dx.doi.org/10.1016/j.compenvurbsys.2018.06.008,PMC6457472,,,"Cities play an important role in fostering and amplifying the transmission of airborne diseases (e.g., influenza) because of dense human contacts. Before an outbreak of airborne diseases within a city, how to determine an appropriate containment area for effective vaccination strategies is unknown. This research treats airborne disease spreads as geo-social interaction patterns, because viruses transmit among different groups of people over geographical locations through human interactions and population movement. Previous research argued that an appropriate scale identified through human geo-social interaction patterns can provide great potential for effective vaccination. However, little work has been done to examine the effectiveness of such vaccination at large scales (e.g., city) that are characterized by spatially heterogeneous population distribution and movement. This article therefore aims to understand the impact of geo-social interaction patterns on effective vaccination in the urbanized area of Portland, Oregon. To achieve this goal, we simulate influenza transmission on a large-scale location-based social network to 1) identify human geo-social interaction patterns for designing effective vaccination strategies, and 2) and evaluate the efficacy of different vaccination strategies according to the identified geo-social patterns. The simulation results illustrate the effectiveness of vaccination strategies based on geosocial interaction patterns in containing the epidemic outbreak at the source. This research can provide evidence to inform public health approaches to determine effective scales in the design of disease control strategies.",,"['Luo, Wei', 'Gao, Peng', 'Cassels, Susan']",,,,
,PMC,The impact of the built environment on health behaviours and disease transmission in social systems,http://dx.doi.org/10.1098/rstb.2017.0245,PMC6030577,,,"The environment plays an important role in disease dynamics and in determining the health of individuals. Specifically, the built environment has a large impact on the prevention and containment of both chronic and infectious disease in humans and in non-human animals. The effects of the built environment on health can be direct, for example, by influencing environmental quality, or indirect by influencing behaviours that impact disease transmission and health. Furthermore, these impacts can happen at many scales, from the individual to the society, and from the design of the plates we eat from to the design of cities. In this paper, we review the ways that the built environment affects both the prevention and the containment of chronic and infectious disease. We bring examples from both human and animal societies and attempt to identify parallels and gaps between the study of humans and animals that can be capitalized on to advance the scope and perspective of research in each respective field. By consolidating this literature, we hope to highlight the importance of built structures in determining the complex dynamics of disease and in impacting the health behaviours of both humans and animals. This article is part of the theme issue ‘Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour’.",,"['Pinter-Wollman, Noa', 'Jelić, Andrea', 'Wells, Nancy M.']",,,,
,PMC,Amicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome,http://dx.doi.org/10.1165/rcmb.2017-0420TR,PMC6039872,,,"Platelets are essential cellular effectors of hemostasis and contribute to disease as circulating effectors of pathologic thrombosis. These are their most widely known biologic activities. Nevertheless, recent observations demonstrate that platelets have a much more intricate repertoire beyond these traditional functions and that they are specialized for contributions to vascular barrier integrity, organ repair, antimicrobial host defense, inflammation, and activities across the immune continuum. Paradoxically, on the basis of clinical investigations and animal models of disease, some of these newly discovered activities of platelets appear to contribute to tissue injury. Studies in the last decade indicate unique interactions of platelets and their precursor, the megakaryocyte, in the lung and implicate platelets as essential effectors in experimental acute lung injury and clinical acute respiratory distress syndrome. Additional discoveries derived from evolving work will be required to precisely define the contributions of platelets to complex subphenotypes of acute lung injury and to determine if these remarkable and versatile blood cells are therapeutic targets in acute respiratory distress syndrome.",,"['Middleton, Elizabeth A.', 'Rondina, Matthew T.', 'Schwertz, Hansjorg', 'Zimmerman, Guy A.']",,,,
,PMC,Positive End-Expiratory Pressure Lower Than the ARDS Network Protocol Is Associated with Higher Pediatric Acute Respiratory Distress Syndrome Mortality,http://dx.doi.org/10.1164/rccm.201707-1404OC,PMC6034123,,,"Rationale: The ARDS Network (ARDSNet) used a positive end-expiratory pressure (PEEP)/Fi(O(2)) model in many studies. In general, pediatric intensivists use less PEEP and higher Fi(O(2)) than this model. Objectives: To evaluate whether children managed with PEEP lower than recommended by the ARDSNet PEEP/Fi(O(2)) model had higher mortality. Methods: This was a multicenter, retrospective analysis of patients with pediatric acute respiratory distress syndrome (PARDS) managed without a formal PEEP/Fi(O(2)) protocol. Four distinct datasets were combined for analysis. We extracted time-matched PEEP/Fi(O(2)) values, calculating the difference between PEEP level and the ARDSNet-recommended PEEP level for a given Fi(O(2)). We analyzed the median difference over the first 24 hours of PARDS diagnosis against ICU mortality and adjusted for confounding variables, effect modifiers, or factors that may have affected the propensity to use lower PEEP. Measurements and Main Results: Of the 1,134 patients with PARDS, 26.6% were managed with lower PEEP relative to the amount of Fi(O(2)) recommended by the ARDSNet protocol. Patients managed with lower PEEP experienced higher mortality than those who were managed with PEEP levels in line with or higher than recommended by the protocol (P < 0.001). After adjustment for hypoxemia, inotropes, comorbidities, severity of illness, ventilator settings, nitric oxide, and dataset, PEEP lower than recommended by the protocol remained independently associated with higher mortality (odds ratio, 2.05; 95% confidence interval, 1.32–3.17). Findings were similar after propensity-based covariate adjustment (odds ratio, 2.00; 95% confidence interval, 1.24–3.22). Conclusions: Patients with PARDS managed with lower PEEP relative to Fi(O(2)) than recommended by the ARDSNet model had higher mortality. Clinical trials targeting PEEP management in PARDS are needed.",,"['Khemani, Robinder G.', 'Parvathaneni, Kaushik', 'Yehya, Nadir', 'Bhalla, Anoopindar K.', 'Thomas, Neal J.', 'Newth, Christopher J. L.']",,,,
,PMC,Feasibility Assessment of a New Surveillance Tool for Respiratory Protective Devices Used in U.S. Healthcare,,PMC6145473,,,"BACKGROUND: Respiratory protective devices (RPDs) are used for infection prevention in healthcare settings during routine patient care and public health emergencies. In recent years, healthcare systems have experienced shortages of RPDs during outbreaks of infectious diseases, in part due to a lack of information about their availability. New tools to track RPD inventories may improve accessibility during an emergency. Investigators at Vanderbilt University have identified four major themes that influence RPD use for infection prevention: hospital preparedness, responsiveness to airborne pathogens, potential exposure outcomes, and infection control practices related to respirator effectiveness. Based on these findings, an RPD surveillance tool (RST) was developed to collect and share near real-time data about RPD supplies in healthcare facilities. The objective of this study was to conduct a feasibility assessment of this RST. METHODS: The new online surveillance tool was implemented at four large, urban, acute care U.S. hospitals in January 2014; data was collected about RPD inventory, tracking systems, hospital characteristics, and utility of gathered information. RESULTS: The RST was implemented successfully and without difficulty at hospitals that had 78 to 90 percent occupancy rates. Participating hospitals reported that the RST (1) provided value for benchmarking their RPD supply, (2) promoted understanding about RPD accessibility among hospital systems engaged in infection control, and (3) served as a means to assess RPD program quality. CONCLUSION: Implementation of this newly developed RST is feasible and appears to have utility in U.S. hospitals for tracking and understanding RPD use for routine healthcare delivery and public health emergencies.",,"['Wizner, Kerri', 'Radonovich, Lewis', 'Bell, Allie', 'Oke, Charles', 'Yarbrough, Mary']",,,,
,PMC,Viral infection in community acquired pneumonia patients with fever: a prospective observational study,http://dx.doi.org/10.21037/jtd.2018.06.33,PMC6105945,,,"BACKGROUND: Patients with community acquired pneumonia (CAP) caused by viruses can develop severe complications, which result in hospitalization and death. The purpose of this study was to analyse the aetiology, incidence, clinical characteristics, and outcomes of CAP patients with fever during non-pandemics, and then to provide theoretical basis for accurate diagnosis and treatment in CAP patients. METHODS: An enrolment system was established for monitoring the CAP patients with fever. Multiplex polymerase chain reaction (mPCR) kits were used to detect 10 viruses [influenza A and B, adenovirus (ADV), respiratory syncytial virus (RSV) A and B, picornavirus, parainfluenza virus (PIV), coronavirus, human metapneumovirus (HMPV), and bocavirus]. Data on age, gender, underlying diseases, complications, laboratory indexes, and outcomes were collected by physicians. RESULTS: This prospective study included 320 patients with fever. Among them, 23.4% were viral-positive by mPCR, with influenza virus most prominent followed by picornavirus. Strong variation in seasonal distribution was shown in viral infections, with peak months from December to February. Patients with influenza infection were likely to be taken to emergency rooms and have respiratory failure with higher creatinine kinase levels and lower white blood cell counts. Streptococcus pneumoniae followed by haemophilus influenzae were the most common bacteria in viral co-infections, which accounted for one third of virus-positive patients. Viral CAP and mixed CAP were not independent factors for death. In addition, lactate dehydrogenase (LDH) >246 IU/L [odds ratio (OR) =7.06, 95% confidence interval (CI): 2.15–23.2, P=0.001], and serum calcium <2.18 mmol/L (OR =6.67, 95% CI: 1.42–31.3, P=0.016) were associated with death. CONCLUSIONS: Viruses play an important role in CAP patients with fever, a systematic clinical, radiological and biological analysis of these patients can contribute to effective therapy that may prevent the development of CAP and improve the outcomes. The present work showed an elaborate analysis evidence of viral infection among fever CAP inpatients.",,"['Tao, Ru-Jia', 'Luo, Xiao-Li', 'Xu, Wen', 'Mao, Bei', 'Dai, Ruo-Xuan', 'Li, Cheng-Wei', 'Yu, Li', 'Gu, Fen', 'Liang, Shuo', 'Lu, Hai-Wen', 'Chen, Ke-Bin', 'Bai, Jiu-Wu', 'Ji, Xiao-Bin', 'Gu, Shu-Yi', 'Sun, Xiao-Li', 'Dai, Fa-Hui', 'Jiang, Ping', 'Cao, Wei-Jun', 'Xu, Jin-Fu']",,,,
,PMC,Ventilation control for airborne transmission of human exhaled bio-aerosols in buildings,http://dx.doi.org/10.21037/jtd.2018.01.24,PMC6072925,,,"The emergence of respiratory diseases, i.e., severe acute respiratory syndrome (SARS) epidemic in 2003, H1N1 influenza epidemic in 2011 and Middle East respiratory syndrome (MERS) outbreak, reiterated the significance of ventilation in buildings. The role of ventilation in removing exhaled airborne bio-aerosols and preventing cross infections has been multidisciplinary extensively studied after the SARS outbreak in 2003. The characteristics of droplet-borne, short-range airborne and long-range airborne transmission of infectious diseases were identified. Increasing ventilation rate can effectively reduce the risk of long-range airborne transmission, while it may be of little useful in preventing the droplet-borne transmission. To maintain the airflow direction from clean cubicles to dirty cubicles is an effective way to prevent the cross infection between cubicles, which is widely used in hospital isolation rooms. Field measurements showed that wrong air flow direction was due to poor construction quality or maintenance. The impacts of different airflow patterns on removing large droplets and fine droplet nuclei were discussed. Some new concepts in general ventilation systems and local personalized equipment were also introduced. This review updates current knowledge of the airborne transmission of pathogens and the improvement of ventilation efficiency concerning the infection prevention.",,"['Qian, Hua', 'Zheng, Xiaohong']",,,,
,PMC,Current understanding of middle east respiratory syndrome coronavirus infection in human and animal models,http://dx.doi.org/10.21037/jtd.2018.03.80,PMC6072923,,,"Middle East respiratory syndrome (MERS) is a highly lethal respiratory disease caused by a novel betacoronavirus (MERS coronavirus, MERS-CoV). Since its first emergence in 2012, multiple transmission events of MERS-CoV (dromedary to human and human to human) have been reported, indicating that MERS-CoV has the potential to cause widespread outbreak. However, the epidemiology of MERS as well as immune responses against the virus in animal models and patients are still not well understood, hindering the vaccine and therapeutic developments. In this review, we summarize recent genetic and epidemic findings of MERS-CoV and the progress in animal model development, immune response studies in both animals and humans. At last, we discussed the breakthrough on vaccine and therapeutic development which are important against potential future MERS outbreak.",,"['Wang, Yanqun', 'Sun, Jing', 'Zhu, Airu', 'Zhao, Jingxian', 'Zhao, Jincun']",,,,
,PMC,Re-understanding anti-influenza strategy: attach equal importance to antiviral and anti-inflammatory therapies,http://dx.doi.org/10.21037/jtd.2018.03.169,PMC6072919,,,"The direct replication of influenza virus is not the only cause of harm to human health; influenza infection leading to a hyper-inflammatory immune response can also result in serious conditions. So, the treatment strategy for influenza needs to keep balance between antivirus and anti-inflammation. Herein, we review the treatment strategies of anti-influenza drugs and traditional Chinese medicines.",,"['Li, Zhengtu', 'Li, Li', 'Zhao, Shuai', 'Li, Jing', 'Zhou, Hongxia', 'Zhang, Yunhui', 'Yang, Zifeng', 'Yuan, Bing']",,,,
,PMC,"One century after 1918 flu pandemic, an ultimate solution remains pending...",http://dx.doi.org/10.21037/jtd.2018.07.57,PMC6072918,,,,,"['Chen, Ling', 'Yang, Zifeng']",,,,
,PMC,Nucleocapsid protein from porcine epidemic diarrhea virus isolates can antagonize interferon-λ production by blocking the nuclear factor-κB nuclear translocation,http://dx.doi.org/10.1631/jzus.B1700283,PMC6052364,,,"Porcine epidemic diarrhea virus (PEDV) is a highly infectious pathogen that can cause severe diseases in pigs and result in enormous economic losses in the worldwide swine industry. Previous studies revealed that PEDV exhibits an obvious capacity for modulating interferon (IFN) signaling or expression. The newly discovered type III IFN, which plays a crucial role in antiviral immunity, has strong antiviral activity against PEDV proliferation in IPEC-J2 cells. In this study, we aimed to investigate the effect of PEDV nucleocapsid (N) protein on type III IFN-λ. We found that the N proteins of ten PEDV strains isolated between 2013 and 2017 from different local farms shared high nucleotide identities, while the N protein of the CV777 vaccine strain formed a monophyletic branch in the phylogenetic tree. The N protein of the epidemic strain could antagonize type III IFN, but not type I or type II IFN expression induced by polyinosinic-polycytidylic acid (poly(I:C)) in IPEC-J2 cells. Subsequently, we demonstrated that the inhibition of poly(I:C)-induced IFN-λ3 production by PEDV N protein was dependent on the blocking of nuclear factor-κB (NF-κB) nuclear translocation. These findings might help increase understanding of the pathogenesis of PEDV and its mechanisms for evading the host immune response.",,"['Shan, Ying', 'Liu, Zi-qi', 'Li, Guo-wei', 'Chen, Cong', 'Luo, Hao', 'Liu, Ya-jie', 'Zhuo, Xun-hui', 'Shi, Xing-fen', 'Fang, Wei-huan', 'Li, Xiao-liang']",,,,
,PMC,"A Snapshot of Influenza Surveillance, Vaccine Recommendations, and Vaccine Access, Drivers, and Barriers in Selected Middle Eastern and North African Countries",http://dx.doi.org/10.5001/omj.2018.54,PMC6047181,,,"OBJECTIVES: Influenza is a vaccine-preventable acute respiratory viral infection that causes epidemics annually around the globe. A regional influenza stakeholder network (MENA-ISN) comprised of experts assessed the status of influenza prevention and control using a structured survey. METHODS: A survey questionnaire was used to obtain information from each participating country on surveillance system, the burden of disease, influenza vaccination programs, recommendations, funding and access for vaccine and vaccination, target rate, coverage rate monitoring, and drivers and barriers to influenza vaccination. RESULTS: Out of the 10 countries that participated, nine had an influenza surveillance system and vaccination policy, and seven had World Health Organization (WHO) accredited reference laboratory. Three countries had burden of disease data available and eight had a reimbursement vaccine policy. Influenza vaccine was available in five countries through the Ministry of Health whereas in others, pharmacies also dispensed for the private sector. In all countries, prescribers were physicians, and vaccinators, which could be physicians, nurses, and pharmacists. Eight countries had a set vaccination target rate and only three monitored the influenza coverage rates. Drivers and barriers of vaccination were similar in all countries. CONCLUSIONS: Despite existing policies, influenza vaccination coverage remains far below the WHO recommendations. Increased awareness and effective implementation of policies with collaboration of stakeholders can help increase the rates to reach WHO targets.",,"['Al Awaidy, Salah', 'Althaqafi, Abdulhakim', 'Dbaibo, Ghassan', None]",,,,
,PMC,Viral Macrodomains: Unique Mediators of Viral Replication and Pathogenesis,http://dx.doi.org/10.1016/j.tim.2017.11.011,PMC6003825,,,"Viruses from the Coronaviridae, Togaviridae, and Hepeviridae families all encode genes that contain a conserved protein domain, called a macrodomain; however, the role of this domain during infection has remained enigmatic. The recent discovery that mammalian macrodomain proteins enzymatically remove ADP-ribose, a common post-translation modification, from proteins has led to an outburst of studies describing both the enzymatic activity and function of viral macrodomains. These new studies have defined these domains as de-ADP-ribosylating enzymes, which indicates that these viruses have evolved to counteract antiviral ADP-ribosylation, likely mediated by poly-ADP-ribose polymerases (PARPs). Here, we will comprehensively review this rapidly expanding field, describing the structures and enzymatic activities of viral macrodomains, and discussing their roles in viral replication and pathogenesis.",,"['Fehr, Anthony R.', 'Jankevicius, Gytis', 'Ahel, Ivan', 'Perlman, Stanley']",,,,
,PMC,Xenotransplantation panel for the detection of infectious agents in pigs,http://dx.doi.org/10.1111/xen.12427,PMC6166664,,,"Recent advances in xenotransplantation have produced organs from pigs that are well tolerated in primate models because of genetic changes engineered to delete major antigens from donor animals. To ensure the safety of human transplant recipients, it will be essential to understand both the spectrum of infectious agents in donor pigs and their potential to be transmitted to immunocompromised transplant recipients. Equally important will be the development of new highly sensitive diagnostic methods for use in the detection of these agents in donor animals and for the monitoring of transplant recipients. Herein, we report results from a panel of 30 quantitative polymerase chain reaction (qPCR) assays for infectious agents with the potential to be transmitted to the human host. The reproducibility, sensitivity and specificity of each assay were evaluated and were found to exhibit analytic sensitivity that was similar to that of quantitative assays used to perform viral load testing of human viruses in clinical laboratories. This analytical approach was used to detect nucleic acids of infectious agents present in specimens from 9 sows and 22 piglets derived by caesarean section. The most commonly detected targets in adult animals were Mycoplasma species and two distinct herpesviruses, porcine lymphotrophic herpesvirus 2 and 3. A total of 14 piglets were derived from three sows infected with either or both herpesviruses, yet none tested positive for the viruses indicating that vertical transmission of these viruses is inefficient.",,"['Hartline, Caroll B.', 'Conner, Ra’Shun L.', 'James, Scott H.', 'Potter, Jennifer', 'Gray, Edward', 'Estrada, Jose', 'Tector, Mathew', 'Tector, A. Joseph', 'Prichard, Mark N.']",,,,
,PMC,Development and evaluation of armored RNA‐based standards for quantification of BCR‐ABL1 (p210/p190) fusion gene transcripts,http://dx.doi.org/10.1002/jcla.22612,PMC6816845,,,"BACKGROUND: Standards play an important role in detection of the BCR‐ABL1 fusion gene (FG) transcript. However, the standards widely used in laboratories are mainly based on plasmids or cDNA, which cannot accurately reflect the process of RNA extraction and cDNA synthesis. Therefore, we aimed to develop armored RNA‐based standards for p210 and p190 BCR‐ABL1 FG transcripts’ quantification. METHODS: Using overlapping polymerase chain reaction (PCR) technology, we first linked a segment of the p210 or p190 BCR‐ABL1 FG transcript with four control genes (CGs; ABL1,BCR,GUSB, and B2M) to form p210FG‐CG and p190FG‐CG. Subsequently, using armored RNA technology, we prepared p210FG‐CG‐ and p190FG‐CG‐armored RNAs and the p210FG‐CG and p190FG‐CG standards, the values of which were assigned by digital PCR (dPCR). RESULTS: The p210FG‐CG and p190FG‐CG standards were stable and homogeneous, and were significantly linear with r (2) > 0.98. A field trial including 52 laboratories across China showed that the coefficient of variation (CV%) of BCR‐ABL1 values among samples was in the range of 58.6%‐129.6% for p210 samples and 73.2%‐194.0% for p190 samples when using local standards. By contrast, when using the p210FG‐CG and p190FG‐CG standards, the CV% of BCR‐ABL1 values was decreased to 35.6%‐124.9% and 36.6%‐170.6% for p210 and p190 samples, respectively. In addition, 33.3% (3/9) of the p210 and p190 samples had CV% values <50.0%, whereas 44.4% (4/9) and 77.8% (7/9) of the samples had lower CV% values when using the p210FG‐CG and p190FG‐CG standards. CONCLUSION: The overall variability of detection of BCR‐ABL1 transcripts decreased significantly when using the p210FG‐CG or p190FG‐CG standards, especially the p190FG‐CG standard.",,"['Fu, Yu', 'Zhang, Rui', 'Wu, Qisheng', 'Zhang, Jiawei', 'Bao, Lihua', 'Li, Jinming']",,,,
,PMC,Complexities of Viral Mutation Rates,http://dx.doi.org/10.1128/JVI.01031-17,PMC6026756,,,"Many viruses evolve rapidly. This is due, in part, to their high mutation rates. Mutation rate estimates for over 25 viruses are currently available. Here, we review the population genetics of virus mutation rates. We specifically cover the topics of mutation rate estimation, the forces that drive the evolution of mutation rates, and how the optimal mutation rate can be context-dependent.",,"['Peck, Kayla M.', 'Lauring, Adam S.']",,,,
,PMC,Structural and Functional Features of the Reovirus σ1 Tail,http://dx.doi.org/10.1128/JVI.00336-18,PMC6026731,,,"Mammalian orthoreovirus attachment to target cells is mediated by the outer capsid protein σ1, which projects from the virion surface. The σ1 protein is a homotrimer consisting of a filamentous tail, which is partly inserted into the virion; a body domain constructed from β-spiral repeats; and a globular head with receptor-binding properties. The σ1 tail is predicted to form an α-helical coiled coil. Although σ1 undergoes a conformational change during cell entry, the nature of this change and its contributions to viral replication are unknown. Electron micrographs of σ1 molecules released from virions identified three regions of flexibility, including one at the midpoint of the molecule, that may be involved in its structural rearrangement. To enable a detailed understanding of essential σ1 tail organization and properties, we determined high-resolution structures of the reovirus type 1 Lang (T1L) and type 3 Dearing (T3D) σ1 tail domains. Both molecules feature extended α-helical coiled coils, with T1L σ1 harboring central chloride ions. Each molecule displays a discontinuity (stutter) within the coiled coil and an unexpectedly seamless transition to the body domain. The transition region features conserved interdomain interactions and appears rigid rather than highly flexible. Functional analyses of reoviruses containing engineered σ1 mutations suggest that conserved residues predicted to stabilize the coiled-coil-to-body junction are essential for σ1 folding and encapsidation, whereas central chloride ion coordination and the stutter are dispensable for efficient replication. Together, these findings enable modeling of full-length reovirus σ1 and provide insight into the stabilization of a multidomain virus attachment protein. IMPORTANCE While it is established that different conformational states of attachment proteins of enveloped viruses mediate receptor binding and membrane fusion, less is understood about how such proteins mediate attachment and entry of nonenveloped viruses. The filamentous reovirus attachment protein σ1 binds cellular receptors; contains regions of predicted flexibility, including one at the fiber midpoint; and undergoes a conformational change during cell entry. Neither the nature of the structural change nor its contribution to viral infection is understood. We determined crystal structures of large σ1 fragments for two different reovirus serotypes. We observed an unexpectedly tight transition between two domains spanning the fiber midpoint, which allows for little flexibility. Studies of reoviruses with engineered changes near the σ1 midpoint suggest that the stabilization of this region is critical for function. Together with a previously determined structure, we now have a complete model of the full-length, elongated reovirus σ1 attachment protein.",,"['Dietrich, Melanie H.', 'Ogden, Kristen M.', 'Long, Jacob M.', 'Ebenhoch, Rebecca', 'Thor, Alexandra', 'Dermody, Terence S.', 'Stehle, Thilo']",,,,
,PMC,Stress Granule Formation is One of the Early Antiviral Mechanisms for Host Cells Against Coxsackievirus B Infection,http://dx.doi.org/10.1007/s12250-018-0040-3,PMC6178097,,,"Stress granules (SGs) are intracellular granules formed when cellular translation is blocked and have been reported to be involved in a variety of viral infections. Our previous studies revealed that SGs are involved in the coxsackievirus B (CVB) infection process, but the role of SGs in CVB infection has not been fully explored. In this study, we found that CVB type 3 (CVB3) could induce SG formation in the early phase of infection. Results showed that levels of CVB3 RNA and protein were significantly inhibited during the early stage of CVB3 infection by the elevated formation of SGs, while viral RNA and protein synthesis were significantly promoted when SG formation was blocked. Our findings suggest that SG formation is one of the early antiviral mechanisms for host cells against CVB infection.",,"['Zhai, Xia', 'Wu, Shuo', 'Lin, Lexun', 'Wang, Tianying', 'Zhong, Xiaoyan', 'Chen, Yang', 'Xu, Weizhen', 'Tong, Lei', 'Wang, Yan', 'Zhao, Wenran', 'Zhong, Zhaohua']",,,,
,PMC,Impact of gut colonization with butyrate-producing microbiota on respiratory viral infection following allo-HCT,http://dx.doi.org/10.1182/blood-2018-01-828996,PMC6024637,,,"Respiratory viral infections are frequent in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) and can potentially progress to lower respiratory tract infection (LRTI). The intestinal microbiota contributes to resistance against viral and bacterial pathogens in the lung. However, whether intestinal microbiota composition and associated changes in microbe-derived metabolites contribute to the risk of LRTI following upper respiratory tract viral infection remains unexplored in the setting of allo-HCT. Fecal samples from 360 allo-HCT patients were collected at the time of stem cell engraftment and subjected to deep, 16S ribosomal RNA gene sequencing to determine microbiota composition, and short-chain fatty acid levels were determined in a nested subset of fecal samples. The development of respiratory viral infections and LRTI was determined for 180 days following allo-HCT. Clinical and microbiota risk factors for LRTI were subsequently evaluated using survival analysis. Respiratory viral infection occurred in 149 (41.4%) patients. Of those, 47 (31.5%) developed LRTI. Patients with higher abundances of butyrate-producing bacteria were fivefold less likely to develop viral LRTI, independent of other factors (adjusted hazard ratio = 0.22, 95% confidence interval 0.04-0.69). Higher representation of butyrate-producing bacteria in the fecal microbiota is associated with increased resistance against respiratory viral infection with LRTI in allo-HCT patients.",,"['Haak, Bastiaan W.', 'Littmann, Eric R.', 'Chaubard, Jean-Luc', 'Pickard, Amanda J.', 'Fontana, Emily', 'Adhi, Fatima', 'Gyaltshen, Yangtsho', 'Ling, Lilan', 'Morjaria, Sejal M.', 'Peled, Jonathan U.', 'van den Brink, Marcel R.', 'Geyer, Alexander I.', 'Cross, Justin R.', 'Pamer, Eric G.', 'Taur, Ying']",,,,
,PMC,Characterisation of porcine epidemic diarrhea virus isolates during the 2014–2015 outbreak in the Philippines,http://dx.doi.org/10.1007/s13337-018-0470-4,PMC6111962,,,"The viral agent of the porcine epidemic diarrhea (PED) was investigated during the reported 2014–2015 outbreaks in commercial farms in Central Luzon, Philippines. The study covered detection of PED virus (PEDV) in fecal and intestinal samples through reverse transcription PCR and sequence analysis of the nucleocapsid (N) gene. Results showed that 10 out of 34 fecal and intestinal samples examined were positive for PEDV. The partial nucleotide sequence of the N gene of the field samples showed 98–99% homologous to PEDV sequences registered in the GenBank. It was also noted that N gene sequences between field samples were 98% homologous. Interestingly, the partial sequences of the N genes of the field samples were genetically similar to the PEDV isolates from USA, China, Mexico, Canada and Japan. The phylogenetic tree analysis revealed that the Philippine samples clustered in group 2–1 of the PEDV, wherein the isolates of this group were responsible for the outbreaks in Asia and the USA. Analysis of the partial nucleotide and amino acid sequences revealed polymorphisms, deletions and insertions in the N-gene of the PEDV. Amino acid sequence alignment also showed deletions and insertion in the PEDV detected in the Philippines. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13337-018-0470-4) contains supplementary material, which is available to authorized users.",,"['Garcia, Gemerlyn G.', 'Aquino, Mark Arman D.', 'Balbin, Michelle M.', 'Belotindos, Lawrence P.', 'Supnet, Jonathan G.', 'Mingala, Claro N.']",,,,
,PMC,TRIM Proteins and Their Roles in Antiviral Host Defenses,http://dx.doi.org/10.1146/annurev-virology-092917-043323,PMC6186430,,,"Tripartite motif (TRIM) proteins are a versatile family of ubiquitin E3 ligases involved in a multitude of cellular processes. Studies in recent years have demonstrated that many TRIM proteins play central roles in the host defense against viral infection. While some TRIM proteins directly antagonize distinct steps in the viral life cycle, others regulate signal transduction pathways induced by innate immune sensors, thereby modulating antiviral cytokine responses. Furthermore, TRIM proteins have been implicated in virus-induced autophagy and autophagy-mediated viral clearance. Given the important role of TRIM proteins in antiviral restriction, it is not surprising that several viruses have evolved effective maneuvers to neutralize the antiviral action of specific TRIM proteins. Here, we describe the major antiviral mechanisms of TRIM proteins as well as viral strategies to escape TRIM-mediated host immunity.",,"['van Gent, Michiel', 'Sparrer, Konstantin M.J.', 'Gack, Michaela U.']",,,,
,PMC,Detection of Influenza A and B Viruses and Respiratory Syncytial Virus by Use of Clinical Laboratory Improvement Amendments of 1988 (CLIA)-Waived Point-of-Care Assays: a Paradigm Shift to Molecular Tests,http://dx.doi.org/10.1128/JCM.00367-18,PMC6018333,,,"An accurate laboratory diagnosis of influenza, respiratory syncytial virus (RSV), and other respiratory viruses can help to guide patient management, antiviral therapy, infection prevention strategies, and epidemiologic monitoring. Influenza has been the primary driver of rapid laboratory testing due to its morbidity and mortality across all ages, the availability of antiviral therapy, which must be given early to have an effect, and the constant threat of new pandemic strains. Over the past 30 years, there has been an evolution in viral diagnostic testing, from viral culture to rapid antigen detection, and more recently, to highly sensitive nucleic acid amplification tests (NAAT), as well as a trend to testing at the point of care (POC). Simple rapid antigen immunoassays have long been the mainstay for POC testing for influenza A and B viruses and respiratory syncytial virus (RSV) but have been faulted for low sensitivity. In 2015, the first POC NAAT for the detection of influenza was approved by the Food and Drug Administration (FDA), ushering in a new era. In 2017, the FDA reclassified rapid influenza diagnostic tests (RIDTs) from class I to class II devices with new minimum performance standards and a requirement for annual reactivity testing. Consequently, many previously available RIDTs can no longer be purchased in the United States. In this review, recent developments in Clinical Laboratory Improvement Amendments of 1988 (CLIA)-waived testing for respiratory virus infections will be presented, with the focus on currently available FDA-cleared rapid antigen and molecular tests primarily for influenza A and B viruses and RSV.",,"['Azar, Marwan M.', 'Landry, Marie L.']",,,,
,PMC,In vivo imaging of the pathophysiological changes and neutrophil dynamics in influenza virus-infected mouse lungs,http://dx.doi.org/10.1073/pnas.1806265115,PMC6048509,,,"The pathophysiological changes that occur in lungs infected with influenza viruses are poorly understood. Here we established an in vivo imaging system that combines two-photon excitation microscopy and fluorescent influenza viruses of different pathogenicity. This approach allowed us to monitor and correlate several parameters and physiological changes including the spread of infection, pulmonary permeability, pulmonary perfusion speed, number of recruited neutrophils in infected lungs, and neutrophil motion in the lungs of live mice. Several physiological changes were larger and occurred earlier in mice infected with a highly pathogenic H5N1 influenza virus compared with those infected with a mouse-adapted human strain. These findings demonstrate the potential of our in vivo imaging system to provide novel information about the pathophysiological consequences of virus infections.",,"['Ueki, Hiroshi', 'Wang, I-Hsuan', 'Fukuyama, Satoshi', 'Katsura, Hiroaki', 'da Silva Lopes, Tiago Jose', 'Neumann, Gabriele', 'Kawaoka, Yoshihiro']",,,,
,PMC,Virus-Receptor Interactions: The Key to Cellular Invasion,http://dx.doi.org/10.1016/j.jmb.2018.06.024,PMC6083867,,,"Virus-receptor interactions play a key regulatory role in viral host range, tissue tropism, and viral pathogenesis. Viruses utilize elegant strategies to attach to one or multiple receptors, overcome the plasma membrane barrier, enter, and access the necessary host cell machinery. The viral attachment protein can be viewed as the “key” that unlocks host cells by interacting with the “lock” – the receptor – on the cell surface, and these lock-and-key interactions are critical for viruses to successfully invade host cells. Many common themes have emerged in virus receptor utilization within and across virus families demonstrating that viruses often target particular classes of molecules in order to mediate these events. Common viral receptors include sialylated glycans, cell adhesion molecules (CAMs) such as immunoglobulin superfamily (IgSF) members and integrins, and phosphatidylserine (PtdSer) receptors. The redundancy in receptor usage suggests that viruses target particular receptors or “common locks” to take advantage of their cellular function and also suggests evolutionary conservation. Due to the importance of initial virus interactions with host cells in viral pathogenesis and the redundancy in viral receptor usage, exploitation o f these strategies would be an attractive target for new antiviral therapeutics.",,"Maginnis, Melissa S.",,,,
,PMC,"Design of novel amyloid β aggregation inhibitors using QSAR, pharmacophore modeling, molecular docking and ADME prediction",http://dx.doi.org/10.1007/s40203-018-0049-1,PMC6314802,,,"The inhibition of abnormal amyloid β (Aβ) aggregation has been regarded as a good target to control Alzheimer’s disease. The present study adopted 2D-QSAR, HQSAR and 3D QSAR (CoMFA & CoMSIA) modeling approaches to identify the structural and physicochemical requirements for the potential Aβ aggregation inhibition. A structure-based molecular docking technique is utilized to approve the features that are obtained from the ligand-based techniques on 30 curcumin derivatives. The combined outputs were then used to screen the modified 10 compounds. The 2D QSAR model on curcumin derivatives gave statistical values R(2) = 0.9086 and SEE = 0.1837. The model was further confirmed by Y-randomization test and Applicability domain analysis by the standardization approach. The HQSAR study (Q(2) = 0.615, R(ncv)(2) = 0.931, R(pred)(2) = 0.956) illustrated the important molecular fingerprints for inhibition. Contour maps of 3D QSAR models, CoMFA (Q(2) = 0.687, R(ncv)(2) = 0.787, R(pred)(2) = 0.731) and CoMSIA (Q(2) = 0.743, R(ncv)(2) = 0.972, R(pred)(2) = 0.713), depict that the models are robust and provide explanation of the important features, like steric, electrostatic and hydrogen bond acceptor, which play important role for interaction with the receptor site cavity. The molecular docking study of the curcumin derivatives elucidates the important interactions between the amino acid residues at the catalytic site of the receptor and the ligands, indicating the structural requirements of the inhibitors. The ligand–receptor interactions of top hits were analyzed to explore the pharmacophore features of Aβ aggregation inhibition. The Aβ aggregation inhibitory activities of novel chemical entities were then obtained through inverse QSAR. The newly designed molecules were further screened through machine learning, prediction of toxicity and nature of metabolism to get the proposed six lead compounds.",,"['Aswathy, Lilly', 'Jisha, Radhakrishnan S.', 'Masand, Vijay H.', 'Gajbhiye, Jayant M.', 'Shibi, Indira G.']",,,,
,PMC,Testing for Respiratory Viruses in Adults With Severe Lower Respiratory Infection,http://dx.doi.org/10.1016/j.chest.2018.06.003,PMC6224704,,,"Viral pathogens are a common cause of severe lower respiratory tract infection in adults. Our ability to rapidly and accurately identify viral infections has dramatically improved as slow culture-based techniques have been largely replaced by multiplex high-throughput systems. Given these advances, reevaluation of the role of respiratory viral testing in adults presenting with lower respiratory tract infection is important. This article reviews the potential benefits of testing, provides an overview of the most commonly used diagnostic techniques, and considers whether current evidence supports routine testing.",,"['Walter, James M.', 'Wunderink, Richard G.']",,,,
,PMC,"The parasite-derived rOv-ASP-1 is an effective antigen-sparing CD4(+) T cell-dependent adjuvant for the trivalent inactivated influenza vaccine, and functions in the absence of MyD88 pathway",http://dx.doi.org/10.1016/j.vaccine.2018.05.029,PMC6595497,,,"Vaccination remains the most cost-effective biomedical approach for controlling influenza disease. In times of pandemics, however, these vaccines cannot be produced in sufficient quantities for worldwide use by the current manufacturing capacities and practices. What is needed is the development of adjuvanted vaccines capable of inducing an adequate or better immune response at a decreased antigen dose. Previously we showed that the protein adjuvant rOv-ASP-1 augments influenza-specific antibody titers and survival after virus challenge in both young adult and old-age mice when administered with the trivalent inactivated influenza vaccine (IIV3). In this study we show that a reduced amount of rOv-ASP-1, with 40-times less IIV3 can also induce protection. Apparently the potency of the rOv-ASP-1 adjuvanted IIV3 vaccine is independent of the IIV3-specific Th1/Th2 associated antibody responses, and independent of the presence of HAI antibodies. However, CD4(+) T helper cells were indispensable for the protection. Further, rOv-ASP-1 with or without IIV3 elicited the increased level of various chemokines, which are known chemoattractant for immune cells, into the muscle 4 hours after immunization, and significantly induced the recruitment of monocytes, macrophages and neutrophils into the muscles. The recruited monocytes had higher expression of the activation marker MHCII on their surface as well as CXCR3 and CCR2; receptors for IP-10 and MCP-1, respectively. These results show that the rOv-ASP-1 adjuvant allows substantial antigen sparing of IIV3 by stimulating at the site of injection the accumulation of chemokines and the recruitment of immune cells that can augment the activation of CD4(+) T cell immune responses, essential for the production of antibody responses. Protection elicited by the rOv-ASP-1 adjuvanted IIV3 vaccine also appears to function in the absence of MyD88-signaling. Future studies will attempt to delineate the precise mechanisms by which the rOv-ASP-1 adjuvanted IIV3 vaccine works.",,"['Jain, Sonia', 'George, Parakkal Jovvian', 'Deng, Wangyan', 'Koussa, Joseph', 'Parkhouse, Kaela', 'Hensley, Scott E.', 'Jiang, Jiu', 'Lu, Jie', 'Liu, Zhuyun', 'Wei, Junfei', 'Zhan, Bin', 'Bottazzi, Maria Elena', 'Shen, Hao', 'Lustigman, Sara']",,,,
,PMC,The S Gene Is Necessary but Not Sufficient for the Virulence of Porcine Epidemic Diarrhea Virus Novel Variant Strain BJ2011C,http://dx.doi.org/10.1128/JVI.00603-18,PMC6002738,,,"The recently emerged highly virulent variants of porcine epidemic diarrhea virus (PEDV) have caused colossal economic losses to the worldwide swine industry. In this study, we investigated the viral virulence determinants by constructing a series of chimeric mutants between the highly virulent strain BJ2011C and the avirulent strain CHM2013. When tested in the 2-day-old piglet model, wild-type (WT) BJ2011C caused severe diarrhea and death of the piglets within 72 h. In contrast, its chimeric derivative carrying the S gene from CHM2013 (BJ2011C-S(CHM)) was avirulent to the piglets. Moreover, reciprocal substitution of the BJ2011C S gene (CHM2013-S(BJ)) did not enable CHM2013 to gain any virulence. However, when the whole structural protein-coding region of BJ2011C (CHM2013-SP(BJ)) was swapped, CHM2013 started to gain the ability to efficiently colonize the intestinal tract and caused diarrhea in piglets. A further gain of virulence required additional acquisition of the 3′ untranslated region (UTR) of BJ2011C, and the resultant virus (CHM2013-SP + 3UTR(BJ)) caused more severe diarrhea and death of piglets. Together, our findings suggest that the virulence of PEDV epidemic strains is a multigenic event and that the S gene is only one of the necessary determinants. IMPORTANCE The recently emerged highly virulent PEDV variants are the major cause of the global porcine epidemic diarrhea (PED) pandemic. The S gene of the variants undergoes remarkable variations and has been thought to be the virulence determinant for the enhanced pathogenesis. Our studies here showed that the S gene is only part of the story and that full virulence requires cooperation from other genes. Our findings provide insight into the pathogenic mechanism of the highly virulent PEDV variants and have implications for future vaccine development.",,"['Wang, Di', 'Ge, Xinna', 'Chen, Dongjie', 'Li, Jie', 'Cai, Yueqi', 'Deng, Jin', 'Zhou, Lei', 'Guo, Xin', 'Han, Jun', 'Yang, Hanchun']",,,,
,PMC,"Complex and Dynamic Interactions between Parvovirus Capsids, Transferrin Receptors, and Antibodies Control Cell Infection and Host Range",http://dx.doi.org/10.1128/JVI.00460-18,PMC6002733,,,"Antibody and receptor binding are key virus-host interactions that control host range and determine the success of infection. Canine and feline parvovirus capsids bind the transferrin receptor type 1 (TfR) to enter host cells, and specific structural interactions appear necessary to prepare the stable capsids for infection. Here, we define the details of binding, competition, and occupancy of wild-type and mutant parvovirus capsids with purified receptors and antibodies. TfR-capsid binding interactions depended on the TfR species and varied widely, with no direct relationship between binding affinity and infection. Capsids bound feline, raccoon, and black-backed jackal TfRs at high affinity but barely bound canine TfRs, which mediated infection efficiently. TfRs from different species also occupied capsids to different levels, with an estimated 1 to 2 feline TfRs but 12 black-backed jackal TfRs binding each capsid. Multiple alanine substitutions within loop 1 on the capsid surface reduced TfR binding but substitutions within loop 3 did not, suggesting that loop 1 directly engaged the TfR and loop 3 sterically affected that interaction. Binding and competition between different TfRs and/or antibodies showed complex relationships. Both antibodies 14 and E competed capsids off TfRs, but antibody E could also compete capsids off itself and antibody 14, likely by inducing capsid structural changes. In some cases, the initial TfR or antibody binding event affected subsequent TfR binding, suggesting that capsid structure changes occur after TfR or antibody binding and may impact infection. This shows that precise, host-specific TfR-capsid interactions, beyond simple attachment, are important for successful infection. IMPORTANCE Host receptor binding is a key step during viral infection and may control both infection and host range. In addition to binding, some viruses require specific interactions with host receptors in order to infect, and anti-capsid antibodies can potentially disrupt these interactions, leading to neutralization. Here, we examine the interactions between parvovirus capsids, the receptors from different hosts, and anti-capsid antibodies. We show that interactions between parvovirus capsids and host-specific TfRs vary in both affinity and in the numbers of receptors bound, with complex effects on infection. In addition, antibodies binding to two sites on the capsids had different effects on TfR-capsid binding. These experiments confirm that receptor and antibody binding to parvovirus capsids are complex processes, and the infection outcome is not determined simply by the affinity of attachment.",,"['Callaway, Heather M.', 'Welsch, Kathrin', 'Weichert, Wendy', 'Allison, Andrew B.', 'Hafenstein, Susan L.', 'Huang, Kai', 'Iketani, Sho', 'Parrish, Colin R.']",,,,
,PMC,Discovery of Novel Bat Coronaviruses in South China That Use the Same Receptor as Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.00116-18,PMC6002729,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) has represented a human health threat since 2012. Although several MERS-related CoVs that belong to the same species as MERS-CoV have been identified from bats, they do not use the MERS-CoV receptor, dipeptidyl peptidase 4 (DPP4). Here, we screened 1,059 bat samples from at least 30 bat species collected in different regions in south China and identified 89 strains of lineage C betacoronaviruses, including Tylonycteris pachypus coronavirus HKU4, Pipistrellus pipistrellus coronavirus HKU5, and MERS-related CoVs. We sequenced the full-length genomes of two positive samples collected from the great evening bat, Ia io, from Guangdong Province. The two genomes were highly similar and exhibited genomic structures identical to those of other lineage C betacoronaviruses. While they exhibited genome-wide nucleotide identities of only 75.3 to 81.2% with other MERS-related CoVs, their gene-coding regions were highly similar to their counterparts, except in the case of the spike proteins. Further protein-protein interaction assays demonstrated that the spike proteins of these MERS-related CoVs bind to the receptor DPP4. Recombination analysis suggested that the newly discovered MERS-related CoVs have acquired their spike genes from a DPP4-recognizing bat coronavirus HKU4. Our study provides further evidence that bats represent the evolutionary origins of MERS-CoV. IMPORTANCE Previous studies suggested that MERS-CoV originated in bats. However, its evolutionary path from bats to humans remains unclear. In this study, we discovered 89 novel lineage C betacoronaviruses in eight bat species. We provide evidence of a MERS-related CoV derived from the great evening bat that uses the same host receptor as human MERS-CoV. This virus also provides evidence for a natural recombination event between the bat MERS-related CoV and another bat coronavirus, HKU4. Our study expands the host ranges of MERS-related CoV and represents an important step toward establishing bats as the natural reservoir of MERS-CoV. These findings may lead to improved epidemiological surveillance of MERS-CoV and the prevention and control of the spread of MERS-CoV to humans.",,"['Luo, Chu-Ming', 'Wang, Ning', 'Yang, Xing-Lou', 'Liu, Hai-Zhou', 'Zhang, Wei', 'Li, Bei', 'Hu, Ben', 'Peng, Cheng', 'Geng, Qi-Bin', 'Zhu, Guang-Jian', 'Li, Fang', 'Shi, Zheng-Li']",,,,
,PMC,Arenaviral Nucleoproteins Suppress PACT-Induced Augmentation of RIG-I Function To Inhibit Type I Interferon Production,http://dx.doi.org/10.1128/JVI.00482-18,PMC6002705,,,"RIG-I is a major cytoplasmic sensor of viral pathogen-associated molecular pattern (PAMP) RNA and induces type I interferon (IFN) production upon viral infection. A double-stranded RNA (dsRNA)-binding protein, PACT, plays an important role in potentiating RIG-I function. We have shown previously that arenaviral nucleoproteins (NPs) suppress type I IFN production via their RNase activity to degrade PAMP RNA. We report here that NPs of arenaviruses block the PACT-induced enhancement of RIG-I function to mediate type I IFN production and that this inhibition is dependent on the RNase function of NPs, which is different from that of a known mechanism of other viral proteins to abolish the interaction between PACT and RIG-I. To understand the biological roles of PACT and RIG-I in authentic arenavirus infection, we analyze growth kinetics of recombinant Pichinde virus (PICV), a prototypical arenavirus, in RIG-I knockout (KO) and PACT KO mouse embryonic fibroblast (MEF) cells. Wild-type (WT) PICV grew at higher titers in both KO MEF lines than in normal MEFs, suggesting the important roles of these cellular proteins in restricting virus replication. PICV carrying the NP RNase catalytically inactive mutation could not grow in normal MEFs but could replicate to some extent in both KO MEF lines. The level of virus growth was inversely correlated with the amount of type I IFNs produced. These results suggest that PACT plays an important role in potentiating RIG-I function to produce type I IFNs in order to restrict arenavirus replication and that viral NP RNase activity is essential for optimal viral replication by suppressing PACT-induced RIG-I activation. IMPORTANCE We report here a new role of the nucleoproteins of arenaviruses that can block type I IFN production via their specific inhibition of the cellular protein sensors of virus infection (RIG-I and PACT). Our results suggest that PACT plays an important role in potentiating RIG-I function to produce type I IFNs in order to restrict arenavirus replication. This new knowledge can be exploited for the development of novel antiviral treatments and/or vaccines against some arenaviruses that can cause severe and lethal hemorrhagic fever diseases in humans.",,"['Shao, Junjie', 'Huang, Qinfeng', 'Liu, Xiaoying', 'Di, Da', 'Liang, Yuying', 'Ly, Hinh']",,,,
,PMC,Functional and evolutionary analysis of viral proteins containing a Rossmann‐like fold,http://dx.doi.org/10.1002/pro.3438,PMC6153405,,,"Viruses are the most abundant life form and infect practically all organisms. Consequently, these obligate parasites are a major cause of human suffering and economic loss. Rossmann‐like fold is the most populated fold among α/β‐folds in the Protein Data Bank and proteins containing Rossmann‐like fold constitute 22% of all known proteins 3D structures. Thus, analysis of viral proteins containing Rossmann‐like domains could provide an understanding of viral biology and evolution as well as could propose possible targets for antiviral therapy. We provide functional and evolutionary analysis of viral proteins containing a Rossmann‐like fold found in the evolutionary classification of protein domains (ECOD) database developed in our lab. We identified 81 protein families of bacterial, archeal, and eukaryotic viruses in light of their evolution‐based ECOD classification and Pfam taxonomy. We defined their functional significance using enzymatic EC number assignments as well as domain‐level family annotations.",,"['Medvedev, Kirill E.', 'Kinch, Lisa N.', 'Grishin, Nick V.']",,,,
,PMC,Insights into the Porcine Reproductive and Respiratory Syndrome Virus Viral Ovarian Tumor Domain Protease Specificity for Ubiquitin and Interferon Stimulated Gene Product 15,http://dx.doi.org/10.1021/acsinfecdis.8b00068,PMC6138529,,,"Porcine reproductive and respiratory syndrome (PRRS) is a widespread economically devastating disease caused by PRRS virus (PRRSV). First recognized in the late 1980s, PRRSV is known to undergo somatic mutations and high frequency viral recombination, which leads to many diverse viral strains. This includes differences within viral virulence factors, such as the viral ovarian tumor domain (vOTU) protease, also referred to as the papain-like protease 2. These proteases down-regulate innate immunity by deubiquitinating proteins targeted by the cell for further processing and potentially also acting against interferon stimulated genes (ISGs). Recently, vOTUs from vaccine derivative Ingelvac PRRS® modified live virus (MLV) and the highly pathogenic PRRSV strain JXwn06 were biochemically characterized, revealing a marked difference in activity toward K63 linked polyubiquitin chains and a limited preference for interferon-stimulated gene product 15 (ISG15) substrates. To extend our research, the vOTUs from NADC31 (low virulence) and SDSU73 (moderately virulent) were biochemically characterized using a myriad of ubiquitin and ISG15 related assays. The K63 polyubiquitin cleavage activity profiles of these vOTUs were found to track with the established pathogenesis of MLV, NADC31, SDSU73, and JXwn06 strains. Fascinatingly, NADC31 demonstrated significantly enhanced activity toward ISG15 substrates compared to its counterparts. Utilizing this information and strain differences within the vOTU encoding region, sites were identified that can modulate K63 polyubiquitin and ISG15 cleavage activities. This information represents the basis for new tools to probe the role of vOTUs in the context of PRRSV pathogenesis.",,"['Bester, Stephanie M.', 'Daczkowski, Courtney M.', 'Faaberg, Kay S.', 'Pegan, Scott D.']",,,,
,PMC,Microfluidic Engineering of Exosomes: Editing Cellular Messages for Precision Therapeutics,http://dx.doi.org/10.1039/c8lc00246k,PMC5997967,,,"Study of extracellular vesicles (EVs), particularly exosomes, holds significant promise; however, it is technically challenging to define these small and molecularly diverse nanovesicles. With intrinsic molecular payload and biodegradability, molecular engineering of exosomes opens new avenues for mediating cellular responses and developing novel nano-delivery systems in precision therapeutics. Microfluidic lab-on-chip technology is playing pivotal roles in this emerging field. In this review, we have examined scientific advancements of microfluidic technology for engineering exosomes and assessed future applications and perspectives in developing precision therapeutics; this can serve the community via identification of potential new research areas or technologies that are urgently needed in precision therapeutics.",,"['Zhu, Qingfu', 'Heon, Mikala', 'Zhao, Zheng', 'He, Mei']",,,,
,PMC,Duration of Stay of Patients with Community-Acquired Pneumonia in Influenza Season,http://dx.doi.org/10.5152/TurkThoracJ.2018.17108,PMC6196901,,,"OBJECTIVES: There is a seasonal variation in the incidence of some infectious diseases. We analyzed the impact of influenza season (IS) on duration of stay (DOS) and some other characteristics of patients with community-acquired pneumonia (CAP). MATERIALS AND METHODS: In our retrospective cohort study, we analyzed data of 369 patients with CAP. RESULTS: The mean patient age was 65.5±16.69 years, and 267 (72.4%) patients were male. There was no difference between patients with CAP admitted to hospital and intensive care unit during IS and non-influenza season (NIS) with respect to age, mortality, and DOS. There was no difference in leukocyte and neutrophil counts, C-reactive protein level, and erythrocyte sedimentation rate in different seasons. Although most comorbid disease rates were similar, only cancer, especially lung cancer, was more prevalent in NIS. Bilateral CAP confirmed using thorax computed tomography was more frequent in IS. CONCLUSION: Although more patients with bilateral pneumonias were hospitalized in IS, DOS was not different between IS and NIS.",,"['Tellioğlu, Emel', 'Balcı, Günseli', 'Mertoğlu, Aydan']",,,,
,PMC,"Sentiment, Contents, and Retweets: A Study of Two Vaccine-Related Twitter Datasets",http://dx.doi.org/10.7812/TPP/17-138,PMC6004971,,,"INTRODUCTION: Social media platforms are important channels through which health education about the utility and safety of vaccination is conducted. OBJECTIVE: To investigate if tweets with different sentiments toward vaccination and different contents attract different levels of Twitter users’ engagement (retweets). METHODS: A stratified random sample (N = 1425) of 142,891 #vaccine tweets (February 4, 2010, to November 10, 2016) was manually coded. All 201 tweets with 100 or more retweets from 194,259 #vaccineswork tweets (January 1, 2014, to April 30, 2015) were manually coded. Regression models were applied to identify factors associated with retweet frequency. RESULTS: Among #vaccine tweets, provaccine tweets (adjusted prevalence ratio = 1.5836, 95% confidence interval = 1.2130–2.0713, p < 0.001) and antivaccine tweets (adjusted prevalence ratio = 4.1280, 95% confidence interval = 3.1183–5.4901, p < 0.001) had more retweets than neutral tweets. No significant differences occurred in retweet frequency for content categories among antivaccine tweets. Among 411 links in provaccine tweets, Twitter (53; 12.9%), content curator Trap.it (14; 3.4%), and the Centers for Disease Control and Prevention (8; 1.9%) ranked as the top 3 domains. Among 325 links in antivaccine tweets, social media links were common: Twitter (44; 14.9%), YouTube (25; 8.4%), and Facebook (10; 3.4%). Among highly retweeted #vaccineswork tweets, the most common theme was childhood vaccinations (40%; 81/201); 21% mentioned global vaccination improvement/efforts (42/201); 29% mentioned vaccines can prevent outbreaks and deaths (58/201). CONCLUSION: Engaging social media key opinion leaders to facilitate health education about vaccination in their tweets may allow reaching a wider audience online.",,"['Blankenship, Elizabeth B', 'Goff, Mary Elizabeth', 'Yin, Jinging', 'Tse, Zion Tsz Ho', 'Fu, King-Wa', 'Liang, Hai', 'Saroha, Nitin', 'Fung, Isaac Chun-Hai']",,,,
,PMC,Insight into the evolution of nidovirus endoribonuclease based on the finding that nsp15 from porcine Deltacoronavirus functions as a dimer,http://dx.doi.org/10.1074/jbc.RA118.003756,PMC6078464,,,"Nidovirus endoribonucleases (NendoUs) include nonstructural protein 15 (nsp15) from coronaviruses and nsp11 from arteriviruses, both of which have been reported to participate in the viral replication process and in the evasion of the host immune system. Results from a previous study of coronaviruses SARS-CoV, HCoV-229E, and MHV nsp15 indicate that it mainly forms a functional hexamer, whereas nsp11 from the arterivirus PRRSV is a dimer. Here, we found that porcine Deltacoronavirus (PDCoV) nsp15 primarily exists as dimers and monomers in vitro. Biological experiments reveal that a PDCoV nsp15 mutant lacking the first 27 amino acids of the N-terminal domain (Asn-1–Asn-27) forms more monomers and displays decreased enzymatic activity, indicating that this region is important for its dimerization. Moreover, multiple sequence alignments and three-dimensional structural analysis indicated that the C-terminal region (His-251–Val-261) of PDCoV nsp15 is 10 amino acids shorter and forms a shorter loop than that formed by the equivalent sequence (Gln-259–Phe-279) of SARS-CoV nsp15. This result may explain why PDCoV nsp15 failed to form hexamers. We speculate that NendoUs may have originated from XendoU endoribonucleases (XendoUs) forming monomers in eukaryotic cells, that NendoU from arterivirus gained the ability to form dimers, and that the coronavirus variants then evolved the capacity to assemble into hexamers. We further propose that PDCoV nsp15 may be an intermediate in this evolutionary process. Our findings provide a theoretical basis for improving our understanding of NendoU evolution and offer useful clues for designing drugs and vaccines against nidoviruses.",,"['Zheng, Anjun', 'Shi, Yuejun', 'Shen, Zhou', 'Wang, Gang', 'Shi, Jiale', 'Xiong, Qiqi', 'Fang, Liurong', 'Xiao, Shaobo', 'Fu, Zhen F.', 'Peng, Guiqing']",,,,
,PMC,Middle East respiratory syndrome coronavirus and bat coronavirus HKU9 both can utilize GRP78 for attachment onto host cells,http://dx.doi.org/10.1074/jbc.RA118.001897,PMC6066311,,,"Coronavirus tropism is predominantly determined by the interaction between coronavirus spikes and the host receptors. In this regard, coronaviruses have evolved a complicated receptor-recognition system through their spike proteins. Spikes from highly related coronaviruses can recognize distinct receptors, whereas spikes of distant coronaviruses can employ the same cell-surface molecule for entry. Moreover, coronavirus spikes can recognize a broad range of cell-surface molecules in addition to the receptors and thereby can augment coronavirus attachment or entry. The receptor of Middle East respiratory syndrome coronavirus (MERS-CoV) is dipeptidyl peptidase 4 (DPP4). In this study, we identified membrane-associated 78-kDa glucose-regulated protein (GRP78) as an additional binding target of the MERS-CoV spike. Further analyses indicated that GRP78 could not independently render nonpermissive cells susceptible to MERS-CoV infection but could facilitate MERS-CoV entry into permissive cells by augmenting virus attachment. More importantly, by exploring potential interactions between GRP78 and spikes of other coronaviruses, we discovered that the highly conserved human GRP78 could interact with the spike protein of bat coronavirus HKU9 (bCoV-HKU9) and facilitate its attachment to the host cell surface. Taken together, our study has identified GRP78 as a host factor that can interact with the spike proteins of two Betacoronaviruses, the lineage C MERS-CoV and the lineage D bCoV-HKU9. The capacity of GRP78 to facilitate surface attachment of both a human coronavirus and a phylogenetically related bat coronavirus exemplifies the need for continuous surveillance of the evolution of animal coronaviruses to monitor their potential for human adaptations.",,"['Chu, Hin', 'Chan, Che-Man', 'Zhang, Xi', 'Wang, Yixin', 'Yuan, Shuofeng', 'Zhou, Jie', 'Au-Yeung, Rex Kwok-Him', 'Sze, Kong-Hung', 'Yang, Dong', 'Shuai, Huiping', 'Hou, Yuxin', 'Li, Cun', 'Zhao, Xiaoyu', 'Poon, Vincent Kwok-Man', 'Leung, Sze Pui', 'Yeung, Man-Lung', 'Yan, Jinghua', 'Lu, Guangwen', 'Jin, Dong-Yan', 'Gao, George Fu', 'Chan, Jasper Fuk-Woo', 'Yuen, Kwok-Yung']",,,,
,PMC,Vancomycin Monotherapy May Be Insufficient to Treat Methicillin-resistant Staphylococcus aureus Coinfection in Children With Influenza-related Critical Illness,http://dx.doi.org/10.1093/cid/ciy495,PMC6336914,,,"BACKGROUND: Coinfection with influenza virus and methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening necrotizing pneumonia in children. Sporadic incidence precludes evaluation of antimicrobial efficacy. We assessed the clinical characteristics and outcomes of critically ill children with influenza–MRSA pneumonia and evaluated antibiotic use. METHODS: We enrolled children (<18 years) with influenza infection and respiratory failure across 34 pediatric intensive care units 11/2008–5/2016. We compared baseline characteristics, clinical courses, and therapies in children with MRSA coinfection, non-MRSA bacterial coinfection, and no bacterial coinfection. RESULTS: We enrolled 170 children (127 influenza A, 43 influenza B). Children with influenza–MRSA pneumonia (N = 30, 87% previously healthy) were older than those with non-MRSA (N = 61) or no (N = 79) bacterial coinfections. Influenza–MRSA was associated with increased leukopenia, acute lung injury, vasopressor use, extracorporeal life support, and mortality than either group (P ≤ .0001). Influenza-related mortality was 40% with MRSA compared to 4.3% without (relative risk [RR], 9.3; 95% confidence interval [CI], 3.8–22.9). Of 29/30 children with MRSA who received vancomycin within the first 24 hours of hospitalization, mortality was 12.5% (N = 2/16) if treatment also included a second anti-MRSA antibiotic compared to 69.2% (N = 9/13) with vancomycin monotherapy (RR, 5.5; 95% CI, 1.4, 21.3; P = .003). Vancomycin dosing did not influence initial trough levels; 78% were <10 µg/mL. CONCLUSIONS: Influenza–MRSA coinfection is associated with high fatality in critically ill children. These data support early addition of a second anti-MRSA antibiotic to vancomycin in suspected severe cases.",,"['Randolph, Adrienne G', 'Xu, Ruifei', 'Novak, Tanya', 'Newhams, Margaret M', 'Bubeck Wardenburg, Juliane', 'Weiss, Scott L', 'Sanders, Ronald C', 'Thomas, Neal J', 'Hall, Mark W', 'Tarquinio, Keiko M', 'Cvijanovich, Natalie', 'Gedeit, Rainer G', 'Truemper, Edward J', 'Markovitz, Barry', 'Hartman, Mary E', 'Ackerman, Kate G', 'Giuliano, John S', 'Shein, Steven L', 'Moffitt, Kristin L', None]",,,,
,PMC,Complete genome analysis of Iranian IS-1494 like avian infectious bronchitis virus,http://dx.doi.org/10.1007/s13337-018-0462-4,PMC6111945,,,"The nephropathogenic infectious bronchitis virus (IBV) strain IS-1494 like (variant-2; GI-23) was first isolated in the Middle East (1998). Despite intensive vaccinations, IS-1494 like IBVs are still circulating in Iran (the dominant genotype) and spread to other countries. Here, the full-length genome of this Iranian IS-1494 like IBV was (Mahed) determined to understand its evolutionary relationships. The genome consists of 27,652 nucleotides, with mutations in most of the structural genes. Thirteen open reading frames (ORFs) were predicted in the Mahed isolate (5′ UTR-1a-1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b-3′ UTR). ORFs 4b, 4c, and 6b, which has rarely been reported, were present in the Mahed genome. According to phylogenetic analysis of the full-length genome, 1a, S2, M, E, N protein, Mahed isolate clustered with the QX type strain. Based on the partial 1b, S1, Mahed clustered with the Q1 strain. The full-length genome of Mahed isolate shared the highest sequence homology with Gray and JMK (90.06–90.07%) and was least related to the Vic-s (86.21%). These data show that evolutionary variation because of recombination in IBV plays a major role in the adaptation and origin of IBV leading to new genetic and types of the virus strain. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13337-018-0462-4) contains supplementary material, which is available to authorized users.",,"['Mousavi, Fatemeh Sadat', 'Ghalyanchilangeroudi, Arash', 'Hosseini, Hossein', 'Nayeri Fasaei, Bahar', 'Ghafouri, Seyed Ali', 'Abdollahi, Hamed', 'Fallah-Mehrabadi, Mohammad Hosein', 'Sadri, Naser']",,,,
,PMC,Nasal priming by a murine coronavirus provides protective immunity against lethal heterologous virus pneumonia,http://dx.doi.org/10.1172/jci.insight.99025,PMC6124400,,,"The nasal mucosa is an important component of mucosal immunity. Immunogenic particles in inspired air are known to activate the local nasal mucosal immune system and can lead to sinonasal inflammation; however, little is known about the effect of this activation on the lung immune environment. Here, we showed that nasal inoculation of murine coronavirus (CoV) in the absence of direct lung infection primes the lung immune environment by recruiting activated monocytes (Ly6C(+) inflammatory monocytes) and NK cells into the lungs. Unlike infiltration of these cells into directly infected lungs, a process that requires type I IFN signaling, nasally induced infiltration of Ly6C(+) inflammatory monocytes into the lungs is IFN-I independent. These activated macrophages ingested antigen and migrated to pulmonary lymph nodes, and enhanced both innate and adaptive immunity after heterologous virus infection. Clinically, such nasal-only inoculation of MHV-1 failed to cause pneumonia but significantly reduced mortality and morbidity of lethal pneumonia caused by severe acute respiratory syndrome CoV (SARS-CoV) or influenza A virus. Together, the data indicate that the nose and upper airway remotely prime the lung immunity to protect the lungs from direct viral infections.",,"['Hua, Xiaoyang', 'Vijay, Rahul', 'Channappanavar, Rudragouda', 'Athmer, Jeremiah', 'Meyerholz, David K.', 'Pagedar, Nitin', 'Tilley, Stephen', 'Perlman, Stanley']",,,,
,PMC,Multi-Clade H5N1 Virus-Like Particles: Immunogenicity and Protection against H5N1 Virus and Effects of Beta-Propiolactone,http://dx.doi.org/10.1016/j.vaccine.2018.05.092,PMC6070352,,,"During the past decade, H5N1 highly pathogenic avian influenza (HPAI) viruses have diversified genetically and antigenically, suggesting the need for multiple H5N1 vaccines. However, preparation of multiple vaccines from live H5N1 HPAI viruses is difficult and economically not feasible representing a challenge for pandemic preparedness. Here we evaluated a novel multi-clade recombinant H5N1 VLP design, in which H5 hemagglutinins (HA) and N1 neuraminidase (NA) derived from four distinct clades of H5N1 virus were co-localized within the VLP structure. The multi-clade H5N1 VLPs were prepared by using a recombinant baculovirus expression system and evaluated for functional hemagglutination and neuraminidase enzyme activities, particle size and morphology, as well as for the presence of baculovirus in the purified VLP preparations. To remove residual baculovirus, VLP preparations were treated with beta-propiolactone (BPL). Immunogenicity and efficacy of multi-clade H5N1 VLPs were determined in an experimental ferret H5N1 HPAI challenge model, to ascertain the effect of BPL on immunogenicity and protective efficacy against lethal challenge. Although treatment with BPL reduced immunogenicity of VLPs, all vaccinated ferrets were protected from lethal challenge with influenza A/VietNam/1203/2004 (H5N1) HPAI virus, indicating that multi-clade VLP preparations treated with BPL represent a potential approach for pandemic preparedness vaccines.",,"['Pushko, Peter', 'Tretyakova, Irina', 'Hidajat, Rachmat', 'Sun, Xiangjie', 'Belser, Jessica A.', 'Tumpey, Terrence M.']",,,,
,PMC,Autopsy Biosafety: Recommendations for Prevention of Meningococcal Disease,http://dx.doi.org/10.1177/1925362118782074,PMC6490128,,,"INTRODUCTION: As invasive meningococcal disease progresses rapidly, often affects youth, and has a fairly high mortality rate, such cases are likely to fall under medical examiner/coroner (ME/C) jurisdiction. Morgue personnel may be at risk of contracting secondary meningococcal disease. We review the current scientific literature regarding Neisseria meningitidis infection and provide recommendations for the prevention of meningococcal disease at autopsy. METHODS: A PubMed search utilizing applicable medical subject heading terms was performed retrieving articles for review from the preceding two decades. Pertinent current guidelines from multiple national organizations were also retrieved. RESULTS: Invasive meningococcal disease is transmitted by direct contact with large respiratory droplets or oral secretions. While a surgical mask would normally provide adequate protection from large droplet spread, it does not prevent inhalation of smaller aerosolized particles such as those generated at autopsy. Prosectors are advised to routinely wear N-95 respirator masks or powered respirator hoods. All published cases of secondary meningococcal disease transmission to healthcare workers invariably arose in scenarios in which face masks/respirators were not employed; none of these cases involved meningococcal disease transmission to ME/C or other morgue staff. DISCUSSION: In the event that no mask—or inadequate coverage such as a surgical mask—is employed during autopsy of a decedent suspected/confirmed to have invasive meningococcal disease, antibiotic prophylaxis is advisable. Assuming appropriate personal protective equipment is utilized, chemoprophylaxis is unnecessary. Routine meningococcal vaccination is not recommended, except for ME/C with specified immunocompromising conditions or traveling to hyperendemic/endemic meningococcal regions. Acad Forensic Pathol. 2018 8(2): 328-339",,"['Brooks, Erin G.', 'Utley-Bobak, Suzanne R.']",,,,
,PMC,Addicted to sugar: roles of glycans in the order Mononegavirales,http://dx.doi.org/10.1093/glycob/cwy053,PMC6291800,,,"Glycosylation is a biologically important protein modification process by which a carbohydrate chain is enzymatically added to a protein at a specific amino acid residue. This process plays roles in many cellular functions, including intracellular trafficking, cell–cell signaling, protein folding and receptor binding. While glycosylation is a common host cell process, it is utilized by many pathogens as well. Protein glycosylation is widely employed by viruses for both host invasion and evasion of host immune responses. Thus better understanding of viral glycosylation functions has potential applications for improved antiviral therapeutic and vaccine development. Here, we summarize our current knowledge on the broad biological functions of glycans for the Mononegavirales, an order of enveloped negative-sense single-stranded RNA viruses of high medical importance that includes Ebola, rabies, measles and Nipah viruses. We discuss glycobiological findings by genera in alphabetical order within each of eight Mononegavirales families, namely, the bornaviruses, filoviruses, mymonaviruses, nyamiviruses, paramyxoviruses, pneumoviruses, rhabdoviruses and sunviruses.",,"['Ortega, Victoria', 'Stone, Jacquelyn A', 'Contreras, Erik M', 'Iorio, Ronald M', 'Aguilar, Hector C']",,,,
,PMC,Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology,http://dx.doi.org/10.1152/physrev.00038.2017,PMC6335102,,,"The renin-angiotensin-aldosterone system plays crucial roles in cardiovascular physiology and pathophysiology. However, many of the signaling mechanisms have been unclear. The angiotensin II (ANG II) type 1 receptor (AT(1)R) is believed to mediate most functions of ANG II in the system. AT(1)R utilizes various signal transduction cascades causing hypertension, cardiovascular remodeling, and end organ damage. Moreover, functional cross-talk between AT(1)R signaling pathways and other signaling pathways have been recognized. Accumulating evidence reveals the complexity of ANG II signal transduction in pathophysiology of the vasculature, heart, kidney, and brain, as well as several pathophysiological features, including inflammation, metabolic dysfunction, and aging. In this review, we provide a comprehensive update of the ANG II receptor signaling events and their functional significances for potential translation into therapeutic strategies. AT(1)R remains central to the system in mediating physiological and pathophysiological functions of ANG II, and participation of specific signaling pathways becomes much clearer. There are still certain limitations and many controversies, and several noteworthy new concepts require further support. However, it is expected that rigorous translational research of the ANG II signaling pathways including those in large animals and humans will contribute to establishing effective new therapies against various diseases.",,"['Forrester, Steven J.', 'Booz, George W.', 'Sigmund, Curt D.', 'Coffman, Thomas M.', 'Kawai, Tatsuo', 'Rizzo, Victor', 'Scalia, Rosario', 'Eguchi, Satoru']",,,,
,PMC,"Urban Rodent Surveillance, Climatic Association, and Genomic Characterization of Seoul Virus Collected at U.S. Army Garrison, Seoul, Republic of Korea, 2006–2010",http://dx.doi.org/10.4269/ajtmh.17-0459,PMC6090319,,,"Rodent-borne pathogens pose a critical public health threat in urban areas. An epidemiological survey of urban rodents was conducted from 2006 to 2010 at the U.S. Army Garrison (USAG), Seoul, Republic of Korea (ROK), to determine the prevalence of Seoul virus (SEOV), a rodent-borne hantavirus. A total of 1,950 rodents were captured at USAG, Yongsan, near/in 19.4% (234/1,206) of the numbered buildings. Annual mean rodent infestation rates were the highest for food service facilities, e.g., the Dragon Hill Lodge complex (38.0 rodents) and the Hartell House (18.8 rodents). The brown rat, Rattus norvegicus, accounted for 99.4% (1,939/1,950) of all the rodents captured in the urban area, whereas only 0.6% (11/1,950) of the rodents was house mice (Mus musculus). In November 2006, higher numbers of rats captured were likely associated with climatic factors, e.g., rainfall and temperatures as rats sought harborage in and around buildings. Only 4.7% (34/718) of the rodents assayed for hantaviruses was serologically positive for SEOV. A total of 8.8% (3/34) R. norvegicus were positive for SEOV RNA by reverse transcription polymerase chain reaction, of which two SEOV strains were completely sequenced and characterized. The 3′ and 5′ terminal sequences revealed incomplete complementary genomic configuration. Seoul virus strains Rn10-134 and Rn10-145 formed a monophyletic lineage with the prototype SEOV strain 80-39. Seoul virus Medium segment showed the highest evolutionary rates compared with the Large and Small segments. In conclusion, this report provides significant insights into continued rodent-borne disease surveillance programs that identify hantaviruses for analysis of disease risk assessments and development of mitigation strategies.",,"['Kim, Heung-Chul', 'Kim, Won-Keun', 'No, Jin Sun', 'Lee, Seung-Ho', 'Gu, Se Hun', 'Chong, Sung-Tae', 'Klein, Terry A.', 'Song, Jin-Won']",,,,
,PMC,Engineering the Mucus Barrier,http://dx.doi.org/10.1146/annurev-bioeng-062117-121156,PMC6463277,,,"Mucus selectively controls the transport of molecules, particulate matter, and microorganisms to the underlying epithelial layer. It may be desirable to weaken the mucus barrier to enable effective delivery of drug carriers. Alternatively, the mucus barrier could be strengthened to prevent epithelial interaction with pathogenic microbes or other exogenous materials. The dynamic mucus layer can undergo changes in structure (e.g., pore size) and/or composition (e.g., protein concentrations, mucin glycosylation) in response to stimuli that occur naturally or are purposefully administered, thus altering its barrier function. This review outlines mechanisms by which mucus provides a selective barrier and methods to engineer the mucus layer from the perspective of strengthening or weakening its barrier properties. In addition, strategic design of drug carriers and dosing formulation properties for efficient delivery across the mucus barrier are highlighted and discussed.",,"['Carlson, T.L.', 'Lock, J.Y.', 'Carrier, R.L']",,,,
,PMC,Identification of potential drug targets and inhibitor of the pathogenic bacteria Shigella flexneri 2a through the subtractive genomic approach,http://dx.doi.org/10.1007/s40203-018-0048-2,PMC6314800,,,"Shigella flexneri 2a is one of the most pathogenic bacteria among the Shigella spp., which is responsible for dysentery and causes masses of deaths throughout the world per year. A proper identification of the potential drug targets and inhibitors is crucial for the treatment of the shigellosis due to their emerging multidrug resistance (MDR) patterns. In this study, a systematic subtractive approach was implemented for the identification of novel therapeutic targets of S. flexneri 2a (301) through genome-wide metabolic pathway analysis of the essential genes and proteins. Ligand-based virtual screening and ADMET analyses were also made for the identification of potential inhibitors as well. Initially, we found 70 essential unique proteins as novel targets. After subsequent prioritization, finally we got six unique targets as the potential therapeutic targets and their three-dimensional models were built thereafter. Aspartate-β-semialdehyde dehydrogenase (ASD), was the most potent target among them and used for docking analysis through ligand-based virtual screening. The compound 3 (PubChem CID: 11319750) suited well as the best inhibitor of the ASD through ADMET and enzyme inhibition capacity analysis. To end, we hope that our proposed therapeutic targets and its inhibitors might give some breakthrough to treat shigellosis efficiently in in vitro. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40203-018-0048-2) contains supplementary material, which is available to authorized users.",,"['Oany, Arafat Rahman', 'Mia, Mamun', 'Pervin, Tahmina', 'Hasan, Md. Nazmul', 'Hirashima, Akinori']",,,,
,PMC,"Gross Morphometry, Histomorphometry, and Immunohistochemistry Confirm Early and Persistent Jejunal Crypt Hyperplasia in Poults with Enteritis and Depressed Growth",http://dx.doi.org/10.1637/11759-101717-Reg.1,PMC6176685,,,"Phosphorylated histone 3 (PH3) and cleaved caspase 3 (CCASP3) were used to detect proliferating and apoptotic cells, respectively, in the jejunums of female sibling poults, with and without enteritis and depressed growth, from hatch to day 35. Poults that developed enteritis and depressed growth (SIB flock) were raised on a commercial farm in eastern North Carolina, whereas poults with normal growth and no enteritis (TAU flock) were raised in the Teaching Animal Unit at North Carolina State University College of Veterinary Medicine. Beginning on day 5 through day 35 and at processing, TAU poults were significantly heavier than SIB poults. Jejunal weights, relative jejunal weights, and jejunal densities were greater in SIB poults from day 10 through 35. Jejunal efficiency (body weight /jejunal length) was higher in TAU poults at day 5 and days 10 through 35. Mucosal thickness was greater in SIB poults between days 7 and 21 but greater in TAU poults at days 28 and 35. From day 7 to 35, villus-to-crypt ratios were higher for TAU poults and lower for SIB poults because hyperplastic crypts formed a greater percentage of the mucosa in SIB poults. By day 7, PH3- and CCASP3-positive cells were increased in SIB poults, showing that mucosal changes resulted from combined crypt epithelial hyperplasia and increased apoptosis of villous enterocytes. Findings in this study confirm that enteritis, in the absence of clinical signs, and depressed growth in turkey poults begins by day 7, can be identified microscopically, persists for at least 35 days, is associated with lower processing weights, and has a profound negative effect on turkey growth.",,"['Fletcher, O. J.', 'Mansell, R.', 'Martin, M. P.', 'Borst, L. B.', 'Barnes, H. John', 'Gonzalez, L. M.']",,,,
,PMC,"Hypoglycemia in dogs: Causes, management, and diagnosis",,PMC5949948,,,"Hypogylcemia in dogs is defined as a blood glucose concentration of less than 3.3 mmol/L (60 mg/dL) and is a relatively common problem encountered in veterinary practice. This metabolic disorder can have an array of clinical signs, ranging from subtle abnormalities to a life-threatening emergency. Hypoglycemia can be due to several physiological processes or etiologies. It is imperative that the clinician is astute in diagnosing hypoglycemia, proficient in providing rapid symptomatic treatment (if indicated) and has a clear diagnostic plan to elucidate the underlying cause. This article reviews the pathophysiology, most common etiologies, and emergency management of hypoglycemia, and presents a diagnostic approach for this problem.",,"['Idowu, Olutunbi', 'Heading, Kathryn']",,,,
,PMC,Pancreatitis and Systemic Coronavirus Infection in a Ferret (Mustela putorius furo),http://dx.doi.org/10.30802/AALAS-CM-17-000109,PMC6008714,,,"A 1-y-old spayed female ferret (Mustela putorius furo) was referred for additional diagnostic evaluation after physical examination by the referring veterinarian revealed a cranial abdominal mass. The ferret had a 2-wk history of inappetence, weight loss, and lethargy. On presentation, the ferret was thin, and an approximately 3-cm mass was palpable in the cranial abdomen. No other abnormalities were noted. Abdominal ultrasonography confirmed the presence of a soft-tissue structure, with a moderate blood supply and mesenteric lymphadenopathy. Fine-needle aspirates of the mass were nondiagnostic. Exploratory laparotomy revealed multiple nodules and thickened tissues throughout the mesentery, a thickened and nodular pancreas, and a small amount of free abdominal fluid. Histopathology of mesenteric, lymphatic, and pancreatic biopsies revealed suppurative pancreatitis and necrotizing and pyogranulomatous mesenteric steatitis. Positive immunohistochemistry for feline coronavirus confirmed a diagnosis of ferret systemic coronavirus disease (FSCD). The ferret was treated medically with oral prednisolone, improved dramatically, and was still doing well 22 mo after diagnosis. Although FSCD has been reported extensively, this case is noteworthy for the presence of suppurative pancreatitis and the positive long-term outcome after corticosteroid therapy.",,"['Wills, Sarah E', 'Beaufrère, Hugues H', 'Brisson, Brigitte A', 'Fraser, Russell S', 'Smith, Dale A']",,,,
,PMC,Comprehensive viral enrichment enables sensitive respiratory virus genomic identification and analysis by next generation sequencing,http://dx.doi.org/10.1101/gr.226316.117,PMC5991510,,,"Next generation sequencing (NGS) technologies have revolutionized the genomics field and are becoming more commonplace for identification of human infectious diseases. However, due to the low abundance of viral nucleic acids (NAs) in relation to host, viral identification using direct NGS technologies often lacks sufficient sensitivity. Here, we describe an approach based on two complementary enrichment strategies that significantly improves the sensitivity of NGS-based virus identification. To start, we developed two sets of DNA probes to enrich virus NAs associated with respiratory diseases. The first set of probes spans the genomes, allowing for identification of known viruses and full genome sequencing, while the second set targets regions conserved among viral families or genera, providing the ability to detect both known and potentially novel members of those virus groups. Efficiency of enrichment was assessed by NGS testing reference virus and clinical samples with known infection. We show significant improvement in viral identification using enriched NGS compared to unenriched NGS. Without enrichment, we observed an average of 0.3% targeted viral reads per sample. However, after enrichment, 50%–99% of the reads per sample were the targeted viral reads for both the reference isolates and clinical specimens using both probe sets. Importantly, dramatic improvements on genome coverage were also observed following virus-specific probe enrichment. The methods described here provide improved sensitivity for virus identification by NGS, allowing for a more comprehensive analysis of disease etiology.",,"[""O'Flaherty, Brigid M."", 'Li, Yan', 'Tao, Ying', 'Paden, Clinton R.', 'Queen, Krista', 'Zhang, Jing', 'Dinwiddie, Darrell L.', 'Gross, Stephen M.', 'Schroth, Gary P.', 'Tong, Suxiang']",,,,
,PMC,COPD subpopulations and phenotyping,http://dx.doi.org/10.1016/j.jaci.2018.02.035,PMC5996762,,,"The diagnosis and treatment of Chronic Obstructive Pulmonary Disease (COPD) has been largely based on a “one size fits all” approach. Diagnosis of COPD is based on meeting the physiological criteria of fixed obstruction in forced expiratory flows and treatment focus on symptomatic relief with limited effect on the overall prognosis. However, patients with COPD have distinct features that determine very different evolution of the disease. In this review, we highlight distinct subgroups of COPD characterized by unique pathophysiological derangements, response to treatment and disease progression. It is likely that identification of subgroups of COPD will lead to discovery of highly needed disease modifying therapeutic approaches. We argue that a precision approach that integrates multiple dimensions (clinical, physiological, imaging and endotyping) is needed to move the field forward in this disease.",,"['Segal, Leopoldo N.', 'Martinez, Fernando J.']",,,,
,PMC,Infections after lung transplantation,http://dx.doi.org/10.21037/jtd.2018.05.204,PMC6051843,,,"The good clinical result of lung transplantation is constantly undermined by the high incidence of infection, which negatively impacts on function and survival. Moreover, infections may also have immunological interactions that play a role in the acute rejection and in the development of chronic lung allograft dysfunction. There is a temporal sequence in the types of infection that affects lung allograft: in the first postoperative month bacteria are the most frequent cause of infection; following this phase, cytomegalovirus and Pneumocystis carinii are common. Fungal infections are particularly feared due to their association with bronchial complication and high mortality. Scrupulous postoperative surveillance is mandatory for the successful management of lung transplantation patients with respect to early detection and treatment of infections. This paper is aimed to address clinicians in the management of the major infectious complications that affect the lung transplant population.",,"['Nosotti, Mario', 'Tarsia, Paolo', 'Morlacchi, Letizia Corinna']",,,,
,PMC,Prof. Chung Ming Chu: the potential and burden of ENB in Asia,http://dx.doi.org/10.21037/jtd.2018.05.110,PMC6035922,,,,,"['Liu, Feng', 'Zhong, Jessie']",,,,
,PMC,Autophagy during viral infection — a double-edged sword,http://dx.doi.org/10.1038/s41579-018-0003-6,PMC6907743,,,"Autophagy is a powerful tool that host cells use to defend against viral infection. Double-membrane vesicles, termed autophagosomes, deliver trapped viral cargo to the lysosome for degradation. Specifically, autophagy initiates an innate immune response by cooperating with pattern recognition receptor signalling to induce interferon production. It also selectively degrades immune components associated with viral particles. Following degradation, autophagy coordinates adaptive immunity by delivering virus-derived antigens for presentation to T lymphocytes. However, in an ongoing evolutionary arms race, viruses have acquired the potent ability to hijack and subvert autophagy for their benefit. In this Review, we focus on the key regulatory steps during viral infection in which autophagy is involved and discuss the specific molecular mechanisms that diverse viruses use to repurpose autophagy for their life cycle and pathogenesis.",,"['Choi, Younho', 'Bowman, James W.', 'Jung, Jae U.']",,,,
,PMC,Prediction and identification of human leukocyte antigen-A2-restricted cytotoxic T lymphocyte epitope peptides from the human papillomavirus 58 E7 protein,http://dx.doi.org/10.3892/ol.2018.8875,PMC6036542,,,"Persistent infection with high-risk human papilloma virus (HPV) is the primary cause of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. HPV58 is the third most common HPV genotype in China after HPV16 and HPV18. HPV E6 and E7 are oncoproteins and are constitutively expressed in HPV-associated cancer cells, therefore they are considered to be ideal target antigens for immunotherapy, including HPV therapeutic vaccine. In the present study, human leukocyte antigen (HLA)-A2-restricted cytotoxic T lymphocyte (CTL) epitope peptides were predicted and screened from HPV58 E7 antigen and their immunogenicity was subsequently determined. A total of 6 HLA-A2-binding peptides derived from HPV58 E7 were predicted and selected using 3 different prediction programs. A negative control peptide and PBS were used as two negative controls. Peripheral blood mononuclear cells (PBMCs) with HLA-A2(+) allele were used to detect the specific cellular immune response among the 6 predicted peptides by enzyme-linked immunospot assay (ELISOPT). Following preliminary screening for the predicted peptides, the antigenicity of the peptide HPV58 E7(72-80) was further assessed by an immunoassay to a vaccine contained HPV58 E7 antigen. Specific humoral and cellular immunity were detected using the peptide HPV58 E7(72-80) as the specific antigen. A total of 6 peptides from HPV58 E7 protein were predicted and subsequently named P1 (E7(7-15): TLREYILDL), P2 (E7(14-22): DLHPEPTDL), P3 (E7(69-77): CINSTTTDV), and P4 (E7(72-80): STTTDVRTL), P5 (E7(79-87): TLQQLLMGT) and P6 (E7(83-91): LLMGTCTIV). In the ELISPOT assay on HLA-A2 (+) human PBMCs, interferon (IFN)-γ-production was evident in the P2 and P4 groups. The average numbers of IFN-γ associated spots in the P2 and P4 groups was 50.61±5.37 spot-forming cells (SFC)/1×10(5) and 266±34.42 SFC/1×10(5), respectively. The numbers of spots in the two peptides were significantly increased compared with the other 4 peptides and the control groups (P<0.05). In the further antigenicity verification of P4 (HPV58 E7(72-80)), the peptide only stimulated the humoral immune response of the AD-HPV16/18/58 mE6E7 vaccine containing HPV58 E7 antigen. Compared with the 2 negative control groups (1:400), the antibody titers of the vaccine group (1:25,600) were significantly increased (P<0.05). In cellular immunoassays the average number of IFN-γ associated spots was 143.3±32.13 SFC/1×10(5) in the vaccine group, which was significantly enhanced compared with the PBS group (8±5.29 SFC/1×10(5); P<0.01) and the AD-NC group (28±5.13 SFC/1×10(5); P<0.01). The peptide HPV58 E7(72-80) (STTTDVRTL) displayed sufficient antigenicity to a vaccine contained HPV58 E7 antigen. Therefore, HPV58 E7(72-80) peptide may be considered as a candidate epitope peptide for the construction of HPV58 peptide vaccines.",,"['Wang, He', 'Chen, Lilai', 'Ma, Weihong', 'Zeng, Yue', 'Qin, Lu', 'Chen, Mengjie', 'Li, Li']",,,,
,PMC,The prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) antibodies in dromedary camels in Israel,http://dx.doi.org/10.1111/zph.12482,PMC6274617,,,"Middle East respiratory syndrome coronavirus, MERS-CoV, was identified in Saudi Arabia in 2012, and as of January 29, 2018, there were 2,123 laboratory-confirmed MERS-CoV cases reported to WHO (WHO, 2018, https://www.who.int/emergencies/mers-cov/en/). Multiple studies suggest that dromedary camels are a source for human MERS-CoV infection. MERS-CoV-specific antibodies have been detected in the serum of dromedary camels across Northern Africa and across the Arabian Peninsula. Israel’s geographic location places Israel at risk for MERS-CoV infection. To date, MERS-CoV-related illness has not been reported and the burden of MERS-CoV infection in the Israeli population is unknown. The seroprevalence of MERS-CoV-specific antibodies in Israeli dromedary camels is unknown. The objective of this study was to determine the prevalence of MERS-CoV seropositivity in dromedary camels in Israel. The prevalence of MERS-CoV antibodies in Israeli camels was examined in 71 camel sera collected from four farms across Israel by MERS-CoV-specific microneutralization (Mnt) assay and confirmed by MERS-CoV-specific immunofluorescence assay (IFA). Although this study cannot rule out potential antibody cross-reactivity by IFA, the presence of bovine coronavirus-specific antibodies do not appear to impact detection of MERS-CoV antibodies by Mnt. MERS-CoV neutralizing antibodies were detectable in 51 (71.8%) camel sera, and no association was observed between the presence of neutralizing antibodies and camel age or gender. These findings extend the known range of MERS-CoV circulation in Middle Eastern camels. The high rate of MERS-CoV-specific antibody seropositivity in dromedary camels in the absence of any reported human MERS cases suggests that there is still much to be learned about the dynamics of camel-to-human transmission of MERS-CoV.",,"['Harcourt, Jennifer L.', 'Rudoler, Nir', 'Tamin, Azaibi', 'Leshem, Eyal', 'Rasis, Michal', 'Giladi, Michael', 'Haynes, Lia M.']",,,,
,PMC,Developmental regulation of effector and resident memory T cell generation during pediatric viral respiratory tract infection(),http://dx.doi.org/10.4049/jimmunol.1800396,PMC6039242,,,"Viral respiratory tract infections (VRTI) remain a leading cause of morbidity and mortality among infants and young children. In mice, optimal protection to VRTI is mediated by recruitment of effector T cells to the lungs and respiratory tract, and subsequent establishment of tissue resident memory T cells (Trm) which provide longterm protection. These critical processes of T cell recruitment to the respiratory tract, their role in disease pathogenesis, and establishment of local protective immunity remain undefined in pediatric VRTI. Here we investigated T cell responses in the upper and lower respiratory tract (URT and LRT, respectively) of infants and young children with VRTI, revealing developmental regulation of T cell differentiation and Trm generation in situ. We show a direct concurrence between T cell responses in the URT and LRT, including a preponderance of effector CD8(+)T cells that was associated with disease severity. During infant VRTI, there was an accumulation of terminally differentiated effector cells (Temra) in the URT and LRT with reduced Trm in the early neonatal period, with decreased Temra and increased Trm formation with age during the early years of childhood. Moreover, human infant T cells exhibit increased expression of the transcription factor T-bet compared to adult T cells, suggesting a mechanism for preferential generation of effector over Trm cells. The developmental regulation of respiratory T cell responses as revealed here is important for diagnosing, monitoring and treating VRTI in the critical early life stages.",,"['Connors, Thomas J.', 'Baird, J. Scott', 'Yopes, Margot C.', 'Zens, Kyra D.', 'Pethe, Kalpana', 'Ravindranath, Thyyar M.', 'Ho, Siu-hong', 'Farber, Donna L.']",,,,
,PMC,Porcine Deltacoronavirus Engages the Transmissible Gastroenteritis Virus Functional Receptor Porcine Aminopeptidase N for Infectious Cellular Entry,http://dx.doi.org/10.1128/JVI.00318-18,PMC5974500,,,"Identification of cellular receptors used by coronavirus (CoV) entry into the host cells is critical to an understanding of pathogenesis and to development of intervention strategies. The fourth CoV genus, Deltacoronavirus, evolutionarily related to the Gammacoronavirus, has just been defined recently. In the current study, we demonstrate that porcine aminopeptidase N (pAPN) acts as a cross-genus CoV functional receptor for both enteropathogenic porcine deltacoronovirus (PDCoV) and alphacoronovirus (AlphaCoV) (transmissible gastroenteritis virus [TGEV]) based upon three lines of evidence. First, the soluble S1 protein of PDCoV bound to the surface of target porcine cell lines known to express pAPN as efficiently as TGEV-S1, which could be blocked by soluble pAPN pretreatment. Second, both PDCoV-S1 and TGEV-S1 physically recognized and interacted with pAPN by coimmunoprecipitation in pAPN cDNA-transfected cells and by dot blot hybridization assay. Finally, exogenous expression of pAPN in refractory cells conferred susceptibility to PDCoV-S1 binding and to PDCoV entry and productive infection. PDCoV-S1 appeared to have a lower pAPN-binding affinity and likely consequent lower infection efficiency in pAPN-expressing refractory cells than TGEV-S1, suggesting that there may be differences between these two viruses in the virus-binding regions in pAPN. This study paves the way for dissecting the molecular mechanisms of PDCoV-host interactions and pathogenesis as well as facilitates future vaccine development and intervention strategies against PDCoV infection. IMPORTANCE The emergence of new human and animal coronaviruses is believed to have occurred through interspecies transmission that is mainly mediated by a species-specific receptor of the host. Among the four genera of the Coronavirinae, a couple of functional receptors for the representative members in the genera Alphacoronavirus and Betacoronavirus have been identified, whereas receptors for Gammacoronavirus and Deltacoronavirus, which are believed to originate from birds, are still unknown. Porcine coronaviruses, including the newly discovered porcine deltacoronavirus (PDCoV) associated with diarrhea in newborn piglets, have posed a serious threat to the pork industry in Asia and North America. Here, we report that PDCoV employs the alphacoronavirus TGEV functional receptor porcine aminopeptidase N (pAPN) for cellular entry, demonstrating the usage of pAPN as a cross-genus CoV functional receptor. The identification of the PDCoV receptor provides another example of the expanded host range of CoV and paves the way for further investigation of PDCoV-host interaction and pathogenesis.",,"['Wang, Bin', 'Liu, Yan', 'Ji, Chun-Miao', 'Yang, Yong-Le', 'Liang, Qi-Zhang', 'Zhao, Pengwei', 'Xu, Ling-Dong', 'Lei, Xi-Mei', 'Luo, Wen-Ting', 'Qin, Pan', 'Zhou, Jiyong', 'Huang, Yao-Wei']",,,,
,PMC,Identification of the RNA Pseudoknot within the 3′ End of the Porcine Reproductive and Respiratory Syndrome Virus Genome as a Pathogen-Associated Molecular Pattern To Activate Antiviral Signaling via RIG-I and Toll-Like Receptor 3,http://dx.doi.org/10.1128/JVI.00097-18,PMC5974490,,,"Once infected by viruses, cells can detect pathogen-associated molecular patterns (PAMPs) on viral nucleic acid by host pattern recognition receptors (PRRs) to initiate the antiviral response. Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of porcine reproductive and respiratory syndrome (PRRS), characterized by reproductive failure in sows and respiratory diseases in pigs of different ages. To date, the sensing mechanism of PRRSV has not been elucidated. Here, we reported that the pseudoknot region residing in the 3′ untranslated regions (UTR) of the PRRSV genome, which has been proposed to regulate RNA synthesis and virus replication, was sensed as nonself by retinoic acid-inducible gene I (RIG-I) and Toll-like receptor 3 (TLR3) and strongly induced type I interferons (IFNs) and interferon-stimulated genes (ISGs) in porcine alveolar macrophages (PAMs). The interaction between the two stem-loops inside the pseudoknot structure was sufficient for IFN induction, since disruption of the pseudoknot interaction powerfully dampened the IFN induction. Furthermore, transfection of the 3′ UTR pseudoknot transcripts in PAMs inhibited PRRSV replication in vitro. Importantly, the predicted similar structures of other arterivirus members, including equine arteritis virus (EAV), lactate dehydrogenase-elevating virus (LDV), and simian hemorrhagic fever virus (SHFV), also displayed strong IFN induction activities. Together, in this work we identified an innate recognition mechanism by which the PRRSV 3′ UTR pseudoknot region served as PAMPs of arteriviruses and activated innate immune signaling to produce IFNs that inhibit virus replication. All of these results provide novel insights into innate immune recognition during virus infection. IMPORTANCE PRRS is the most common viral disease in the pork industry. It is caused by PRRSV, a positive single-stranded RNA virus, whose infection often leads to persistent infection. To date, it is not yet clear how PRRSV is recognized by the host and what is the exact mechanism of IFN induction. Here, we investigated the nature of PAMPs on PRRSV and the associated PRRs. We found that the 3′ UTR pseudoknot region of PRRSV, which has been proposed to regulate viral RNA synthesis, could act as PAMPs recognized by RIG-I and TLR3 to induce type I IFN production to suppress PRRSV infection. This report is the first detailed description of pattern recognition for PRRSV, which is important in understanding the antiviral response of arteriviruses, especially PRRSV, and extends our knowledge on virus recognition.",,"['Xie, Sha', 'Chen, Xin-xin', 'Qiao, Songlin', 'Li, Rui', 'Sun, Yangang', 'Xia, Shuangfei', 'Wang, Lin-Jian', 'Luo, Xuegang', 'Deng, Ruiguang', 'Zhou, En-Min', 'Zhang, Gai-Ping']",,,,
,PMC,PNAS Plus Significance Statements,http://dx.doi.org/10.1073/pnas.ss11522,PMC5984556,,,,,,,,,
,PMC,Lassa virus glycoprotein: stopping a moving target,http://dx.doi.org/10.1016/j.coviro.2018.05.002,PMC6193841,,,"The structure of a prefusion arenavirus GPC was enigmatic for many years, owing to the metastable and non-covalent nature of the association between the receptor binding and fusion subunits. Recent engineering efforts to stabilize the glycoprotein of the Old World arenavirus Lassa in a native, yet cleaved state, allowed the first structure of any arenavirus prefusion GPC trimer to be determined. Comparison of this structure with the structures of other arenavirus glycoprotein subunits reveals surprising findings: that the receptor binding subunit, GP1, of Lassa virus is conformationally labile, while the GP1 subunit of New World arenaviruses is not, and that the arenavirus GPC adopts a trimeric state unlike other glycoproteins with similar fusion machinery. Structural analysis, combined with recent biochemical data regarding antibody epitopes and receptor binding requirements, provides a basis for rational vaccine design.",,"['Hastie, Kathryn M', 'Saphire, Erica Ollmann']",,,,
,PMC,Fungicidal Potency and Mechanisms of θ-Defensins against Multidrug-Resistant Candida Species,http://dx.doi.org/10.1128/AAC.00111-18,PMC5971616,,,"Systemic candidiasis is a growing health care concern that is becoming even more challenging due to the growing frequency of infections caused by multidrug-resistant (MDR) Candida species. Thus, there is an urgent need for new therapeutic approaches to candidiasis, including strategies bioinspired by insights into natural host defense against fungal pathogens. The antifungal properties of θ-defensins, macrocyclic peptides expressed in tissues of Old World monkeys, were investigated against a panel of drug-sensitive and drug-resistant clinical isolates of Candida albicans and non-albicans Candida species. Rhesus θ-defensin 1 (RTD-1), the prototype θ-defensin, was rapidly and potently fungicidal against drug-sensitive and MDR C. albicans strains. Fungal killing occurred by cell permeabilization that was temporally correlated with ATP release and intracellular accumulation of reactive oxygen species (ROS). Killing by RTD-1 was compared with that by histatin 5 (Hst 5), an extensively characterized anticandidal peptide expressed in human saliva. RTD-1 killed C. albicans much more rapidly and at a >200-fold lower concentration than that of Hst 5. Unlike Hst 5, the anticandidal activity of RTD-1 was independent of mitochondrial ATP production. Moreover, RTD-1 was completely resistant to Candida proteases for 2 h under conditions that rapidly and completely degraded Hst 5. MICs and minimum fungicidal concentrations (MFCs) of 14 natural θ-defensins isoforms against drug-resistant C. albicans isolates identified peptides that are more active than amphotericin B and/or caspofungin against fluconazole-resistant organisms, including MDR Candida auris. These results point to the potential of macrocyclic θ-defensins as structural templates for the design of antifungal therapeutics.",,"['Basso, Virginia', 'Garcia, Angie', 'Tran, Dat Q.', 'Schaal, Justin B.', 'Tran, Patti', 'Ngole, Diana', 'Aqeel, Younus', 'Tongaonkar, Prasad', 'Ouellette, André J.', 'Selsted, Michael E.']",,,,
,PMC,C6orf106 is a novel inhibitor of the interferon-regulatory factor 3–dependent innate antiviral response,http://dx.doi.org/10.1074/jbc.RA117.001491,PMC6036214,,,"Host recognition of intracellular viral RNA and subsequent induction of cytokine signaling are tightly regulated at the cellular level and are a target for manipulation by viruses and therapeutics alike. Here, we characterize chromosome 6 ORF 106 (C6orf106) as an evolutionarily conserved inhibitor of the innate antiviral response. C6orf106 suppresses the synthesis of interferon (IFN)-α/β and proinflammatory tumor necrosis factor (TNF) α in response to the dsRNA mimic poly(I:C) and to Sendai virus infection. Unlike canonical inhibitors of antiviral signaling, C6orf106 blocks interferon-regulatory factor 3 (IRF3) and, to a lesser extent, NF-κB activity without modulating their activation, nuclear translocation, cellular expression, or degradation. Instead, C6orf106 interacts with IRF3 and inhibits IRF3 recruitment to type I IFN promoter sequences while also reducing the nuclear levels of the coactivator proteins p300 and CREB-binding protein (CBP). In summary, we have defined C6orf106 as a negative regulator of antiviral immunity that blocks IRF3-dependent cytokine production via a noncanonical and poorly defined mechanism. This work presents intriguing implications for antiviral immunity, autoimmune disorders, and cancer.",,"['Ambrose, Rebecca L.', 'Liu, Yu Chih', 'Adams, Timothy E.', 'Bean, Andrew G. D.', 'Stewart, Cameron R.']",,,,
,PMC,Constructing Smart Protocells with Built-In DNA Computational Core to Eliminate Exogenous Challenge,http://dx.doi.org/10.1021/jacs.8b01960,PMC6442726,,,"A DNA reaction network is like a biological algorithm that can respond to “molecular input signals”, such as biological molecules, while the artificial cell is like a microrobot whose function is powered by the encapsulated DNA reaction network. In this work, we describe the feasibility of using a DNA reaction network as the computational core of a protocell, which will perform an artificial immune response in a concise way to eliminate a mimicked pathogenic challenge. Such a DNA reaction network (RN)-powered protocell can realize the connection of logical computation and biological recognition due to the natural programmability and biological properties of DNA. Thus, the biological input molecules can be easily involved in the molecular computation and the computation process can be spatially isolated and protected by artificial bilayer membrane. We believe the strategy proposed in the current paper, i.e., using DNA RN to power artificial cells, will lay the groundwork for understanding the basic design principles of DNA algorithm-based nanodevices which will, in turn, inspire the construction of artificial cells, or protocells, that will find a place in future biomedical research.",,"['Lyu, Yifan', 'Wu, Cuichen', 'Heinke, Charles', 'Han, Da', 'Cai, Ren', 'Teng, I-Ting', 'Liu, Yuan', 'Liu, Hui', 'Zhang, Xiaobing', 'Liu, Qiaoling', 'Tan, Weihong']",,,,
,PMC,"Cryptic Binding Sites on Proteins: Definition, Detection, and Druggability",http://dx.doi.org/10.1016/j.cbpa.2018.05.003,PMC6088748,,,"Many proteins in their unbound structures lack surface pockets appropriately sized for drug binding. Hence, a variety of experimental and computational tools have been developed for the identification of cryptic sites that are not evident in the unbound protein but form upon ligand binding, and can provide tractable drug target sites. The goal of this review is to discuss the definition, detection, and druggability of such sites, and their potential value for drug discovery. Novel methods based on molecular dynamics simulations are particularly promising and yield a large number of transient pockets, but it has been shown that only a minority of such sites are generally capable of binding ligands with substantial affinity. Based on recent studies, current methodology can be improved by combining molecular dynamics with fragment docking and machine learning approaches.",,"['Vajda, Sandor', 'Beglov, Dmitri', 'Wakefield, Amanda E.', 'Egbert, Megan', 'Whitty, Adrian']",,,,
,PMC,Wheat streak mosaic virus: a century old virus with rising importance worldwide,http://dx.doi.org/10.1111/mpp.12683,PMC6638073,,,"Wheat streak mosaic virus (WSMV) causes wheat streak mosaic, a disease of cereals and grasses that threatens wheat production worldwide. It is a monopartite, positive‐sense, single‐stranded RNA virus and the type member of the genus Tritimovirus in the family Potyviridae. The only known vector is the wheat curl mite (WCM, Aceria tosichella), recently identified as a species complex of biotypes differing in virus transmission. Low rates of seed transmission have been reported. Infected plants are stunted and have a yellow mosaic of parallel discontinuous streaks on the leaves. In the autumn, WCMs move from WSMV‐infected volunteer wheat and other grass hosts to newly emerged wheat and transmit the virus which survives the winter within the plant, and the mites survive as eggs, larvae, nymphs or adults in the crown and leaf sheaths. In the spring/summer, the mites move from the maturing wheat crop to volunteer wheat and other grass hosts and transmit WSMV, and onto newly emerged wheat in the fall to which they transmit the virus, completing the disease cycle. WSMV detection is by enzyme‐linked immunosorbent assay (ELISA), reverse transcription‐polymerase chain reaction (RT‐PCR) or quantitative RT‐PCR (RT‐qPCR). Three types of WSMV are recognized: A (Mexico), B (Europe, Russia, Asia) and D (USA, Argentina, Brazil, Australia, Turkey, Canada). Resistance genes Wsm1, Wsm2 and Wsm3 have been identified. The most effective, Wsm2, has been introduced into several wheat cultivars. Mitigation of losses caused by WSMV will require enhanced knowledge of the biology of WCM biotypes and WSMV, new or improved virus detection techniques, the development of resistance through traditional and molecular breeding, and the adaptation of cultural management tactics to account for climate change.",,"['Singh, Khushwant', 'Wegulo, Stephen N.', 'Skoracka, Anna', 'Kundu, Jiban Kumar']",,,,
,PMC,Potential Pathogenicity of Inqulinus limosus in a Pediatric Patient with Cystic Fibrosis,http://dx.doi.org/10.1002/ppul.24043,PMC6219391,,,"PRESENTATION: Patient is a 6-year-old male with CF, MRSA colonization, and pancreatic insufficiency that presented with worsening ppFEV1 and systemic symptoms despite multiple interventions. BAL grew NTM, Stenotrophomonas maltophilia, and Inquilinus limosus, a rare organism found in patients with CF. COURSE: I. limosus treatment was deferred. Despite treatment of other pathogens, symptoms worsened. I. limosus was targeted with meropenem, amikacin, and ciprofloxacin along with clindamycin for MRSA colonization. Within weeks, symptoms had resolved with ppFEV1 improvement. DISCUSSION: This case discusses the importance of a rare organism in the CF population. Targeting I.limosus was key to recovery, revealing its potential pathogenicity.",,"['Poore, T. Spencer', 'Virella-Lowell, Isabel', 'Guimbellot, Jennifer S.']",,,,
,PMC,Top-Down Chemoenzymatic Approach to Synthesizing Diverse High-Mannose N-Glycans and Related Neoglycoproteins for Carbohydrate Microarray Analysis,http://dx.doi.org/10.1021/acs.bioconjchem.8b00145,PMC6013400,,,"High-mannose-type N-glycans are an important component of neutralizing epitopes on HIV-1 envelope glycoprotein gp120. They also serve as signals for protein folding, trafficking, and degradation in protein quality control. A number of lectins and antibodies recognize high-mannose-type N-glycans, and glycan array technology has provided an avenue to probe these oligomannose-specific proteins. We describe in this paper a top-down chemoenzymatic approach to synthesize a library of high-mannose N-glycans and related neoglycoproteins for glycan microarray analysis. The method involves the sequential enzymatic trimming of two readily available natural N-glycans, the Man(9)GlcNAc(2)Asn prepared from soybean flour and the sialoglycopeptide (SGP) isolated from chicken egg yolks, coupled with chromatographic separation to obtain a collection of a full range of natural high-mannose N-glycans. The Asn-linked N-glycans were conjugated to bovine serum albumin (BSA) to provide neoglycoproteins containing the oligomannose moieties. The glycoepitopes displayed were characterized using an array of glycan-binding proteins, including the broadly virus-neutralizing agents, glycan-specific antibody 2G12, Galanthus nivalis lectin (GNA), and Narcissus pseudonarcissus lectin (NPA).",,"['Toonstra, Christian', 'Wu, Lisa', 'Li, Chao', 'Wang, Denong', 'Wang, Lai-Xi']",,,,
,PMC,Peptide and protein nanoparticle conjugates: versatile platforms for biomedical applications,http://dx.doi.org/10.1039/c7cs00877e,PMC6386136,,,"Peptide- and protein-nanoparticle conjugates have emerged as powerful tools for biomedical applications, enabling the treatment, diagnosis, and prevention of disease. In this review, we focus on the key roles played by peptides and proteins in improving, controlling, and defining the performance of nanotechnologies. Within this framework, we provide a comprehensive overview of the key sequences and structures utilised to provide biological and physical stability to nano-constructs, direct particles to their target and influence their cellular and tissue distribution, induce and control biological responses, and form polypeptide self-assembled nanoparticles. In doing so, we highlight the great advances made by the field, as well as the challenges still faced in achieving the clinical translation of peptide- and protein-functionalised nano-drug delivery vehicles, imaging species, and active therapeutics.",,"['Spicer, Christopher D.', 'Jumeaux, Coline', 'Gupta, Bakul', 'Stevens, Molly M.']",,,,
,PMC,Biological species in the viral world,http://dx.doi.org/10.1073/pnas.1717593115,PMC6003344,,,"Due to their dependence on cellular organisms for metabolism and replication, viruses are typically named and assigned to species according to their genome structure and the original host that they infect. But because viruses often infect multiple hosts and the numbers of distinct lineages within a host can be vast, their delineation into species is often dictated by arbitrary sequence thresholds, which are highly inconsistent across lineages. Here we apply an approach to determine the boundaries of viral species based on the detection of gene flow within populations, thereby defining viral species according to the biological species concept (BSC). Despite the potential for gene transfer between highly divergent genomes, viruses, like the cellular organisms they infect, assort into reproductively isolated groups and can be organized into biological species. This approach revealed that BSC-defined viral species are often congruent with the taxonomic partitioning based on shared gene contents and host tropism, and that bacteriophages can similarly be classified in biological species. These results open the possibility to use a single, universal definition of species that is applicable across cellular and acellular lifeforms.",,"['Bobay, Louis-Marie', 'Ochman, Howard']",,,,
,PMC,"Encephalitis is mediated by ROP18 of Toxoplasma gondii, a severe pathogen in AIDS patients",http://dx.doi.org/10.1073/pnas.1801118115,PMC6003310,,,"The neurotropic parasite Toxoplasma gondii is a globally distributed parasitic protozoan among mammalian hosts, including humans. During the course of infection, the CNS is the most commonly damaged organ among invaded tissues. The polymorphic rhoptry protein 18 (ROP18) is a key serine (Ser)/threonine (Thr) kinase that phosphorylates host proteins to modulate acute virulence. However, the basis of neurotropism and the specific substrates through which ROP18 exerts neuropathogenesis remain unknown. Using mass spectrometry, we performed proteomic analysis of proteins that selectively bind to active ROP18 and identified RTN1-C, an endoplasmic reticulum (ER) protein that is preferentially expressed in the CNS. We demonstrated that ROP18 is associated with the N-terminal portion of RTN1-C and specifically phosphorylates RTN1-C at Ser7/134 and Thr4/8/118. ROP18 phosphorylation of RTN1-C triggers ER stress-mediated apoptosis in neural cells. Remarkably, ROP18 phosphorylation of RTN1-C enhances glucose-regulated protein 78 (GRP78) acetylation by attenuating the activity of histone deacetylase (HDAC), and this event is associated with an increase of neural apoptosis. These results clearly demonstrate that both RTN1-C and HDACs are involved in T. gondii ROP18-mediated pathogenesis of encephalitis during Toxoplasma infection.",,"['An, Ran', 'Tang, Yuewen', 'Chen, Lijian', 'Cai, Haijian', 'Lai, De-Hua', 'Liu, Kang', 'Wan, Lijuan', 'Gong, Linli', 'Yu, Li', 'Luo, Qingli', 'Shen, Jilong', 'Lun, Zhao-Rong', 'Ayala, Francisco J.', 'Du, Jian']",,,,
,PMC,Evidence of Australian bat lyssavirus infection in diverse Australian bat taxa,http://dx.doi.org/10.1111/zph.12480,PMC6249124,,,"Historically, Australia was considered free of rabies and rabies-like viruses. Thus, the identification of Australian bat lyssavirus (ABLV) in 1996 in a debilitated bat found by a member of the public precipitated both public health consternation and a revision of lyssavirus taxonomy. Subsequent observational studies sought to elaborate the occurrence and frequency of ABLV infection in Australian bats. This paper describes the taxonomic diversity of bat species showing evidence of ABLV infection to better inform public health considerations. Blood and/or brain samples were collected from two cohorts of bats (wild-caught and diagnostic submissions) from four Australian states or territories between April 1996 and October 2002. Fresh brain impression smears were tested for ABLV antigen using fluorescein-labelled anti-rabies monoclonal globulin (CENTOCOR) in a direct fluorescent antibody test; sera were tested for the presence of neutralising antibodies using a rapid fluorescent focus inhibition test. A total of 3,217 samples from 2,633 bats were collected and screened: brain samples from 1,461 wild-caught bats and 1086 submitted bats from at least 16 genera and seven families, and blood samples from 656 wild-caught bats and 14 submitted bats from 14 genera and seven families. Evidence of ABLV infection was found in five of the six families of bats occurring in Australia, and in three of the four Australian states/territories surveyed, supporting the historic presence of the virus in Australia. While the infection prevalence in the wild-caught cohort is evidently low, the significantly higher infection prevalence in rescued bats in urban settings represents a clear and present public health significance because of the higher risk of human exposure.",,"Field, Hume Ernest",,,,
,PMC,"Screening for Middle East respiratory syndrome coronavirus among febrile Indonesian Hajj pilgrims: A study on 28,197 returning pilgrims",http://dx.doi.org/10.1177/1757177418765634,PMC6109871,,,"There were 211,000 Indonesian Hajj pilgrims going to Mecca through 11 main airports in 2015 who were at risk of contracting the Middle East respiratory syndrome coronavirus (MERS-CoV). We aimed to find out whether there was any occurrence of MERS-CoV by performing screening on 28,197 returning pilgrims. Those with a body temperature of > 38 °C and respiratory symptoms were sent to the airport clinic to have an oropharyngeal swab and a bacterial culture. Fifteen pilgrims had fever (> 38 °C) accompanied by respiratory symptoms; of these, 12 patients were diagnosed with upper and lower respiratory tract infections and three patients with pneumonia. However, none of them were found to be infected with MERS-CoV. The bacterial cultures showed evidence of normal flora growth.",,"['Amin, M', 'Bakhtiar, A', 'Subarjo, M', 'Aksono, EB', 'Widiyanti, P', 'Shimizu, K', 'Mori, Y']",,,,
,PMC,Antibiotic exposure prior to respiratory viral infection is associated with progression to lower respiratory tract disease in allogeneic hematopoietic cell transplant recipients,http://dx.doi.org/10.1016/j.bbmt.2018.05.016,PMC6286157,,,"INTRODUCTION: Recent publications note an association between antibiotic exposure and respiratory viral infections (RVIs). Antibiotics affect microbiota and impair immune response against RVIs in mice, and low microbiome diversity is associated with pulmonary complications including viral lower respiratory tract disease (LRTD) in hematopoietic cell transplantation (HCT) recipients. In this study, we examined whether antibiotic exposure was associated with increased risk of disease progression in RVIs post-transplantation. MATERIALS AND METHODS: We analyzed patients who underwent allogeneic HCT (6/2008-2/2016) and had their first RVI due to parainfluenza virus (PIV), respiratory syncytial virus (RSV) or human metapneumovirus (MPV) during the initial 100 days post-transplantation. Antibiotic exposure in the three weeks before RVI onset was defined as (i) use of specific antibiotics versus none of these antibiotics, and (ii) number of antibiotic-days. Cox proportional hazards models were used to examine associations between antibiotic exposures and risk of viral disease progression to proven/probable/possible LRTD. RESULTS: Ninety HCT recipients (84 adults, 6 children) fulfilled study criteria; 33 progressed to LRTD. The number of antibiotic-days was associated with progression to LRTD after adjusting for neutropenia, steroid use, and either lymphopenia (hazard ratio, 1.41 [95% confidence interval (CI) 1.04–1.92], P=.027) or monocytopenia (hazard ratio, 1.46 [95% CI, 1.11–1.91], P=.006). Specific antibiotic classes was not associated with the outcome. CONCLUSIONS: Cumulative antibiotic exposure immediately before RVI onset is a risk factor for disease progression following PIV, RSV and MPV infections post-transplantation. Larger cohort studies are needed to determine the impact of specific antibiotics/antibiotic classes on disease severity.",,"['Ogimi, Chikara', 'Krantz, Elizabeth M.', 'Golob, Jonathan L.', 'Waghmare, Alpana', 'Liu, Catherine', 'Leisenring, Wendy M.', 'Woodard, Christopher R.', 'Marquis, Sara', 'Kuypers, Jane M.', 'Jerome, Keith R.', 'Pergam, Steven A.', 'Fredricks, David N.', 'Sorror, Mohamed L.', 'Englund, Janet A.', 'Boeckh, Michael']",,,,
,PMC,Health benefits of orally administered anti-IL-10 antibody in in milk-fed dairy calves.,http://dx.doi.org/10.3168/jds.2017-14270,PMC6526946,,,"The primary objective of this randomized controlled trial was to determine if anti-IL-10 egg yolk antibodies fed upon arrival to a calf ranch would lower the prevalence of C. parvum shedding in naturally challenged preweaned dairy calves. Secondary objectives included measuring the effect of anti-IL-10 antibodies on calf health, performance, and shedding of less common diarrheal pathogens. A total of 133 calves, enrolled at 24 – 72 h of age, received a daily dose of 0.96 gm of egg yolk powder with anti-IL-10 antibodies (MAB, n = 71) or without anti-IL-10 antibodies (MEP, n = 62) split between 2 feedings for the first 11 d on feed at a calf ranch. Daily health evaluations were completed for 15 days after arrival and on d 56. Digital weights were collected at enrollment and d 56 and hipometer weights at enrollment, d 7 and 56. Packed cell volume and serum total protein concentration were measured at enrollment, d 7 and 14. Fecal pH was measured at enrollment, d 5 and 14, and fecal pathogen (C. parvum, coronavirus, rotavirus, and Salmonella spp) shedding was assessed at d 5 and 14. Continuous outcomes were compared between groups using a student’s t-test or Wilcoxon rank sum test. Fecal pathogen shedding at d 14, respiratory disease at d 56, and antibiotic usage were compared using relative risk and chi square test. Fecal pH (median, IQR) on d 14 was 6.65 (6.39 – 6.99) and 6.52 (5.97 – 6.81) for MAB and MEP, respectively. On d 56, the risk of respiratory disease was lower for MAB compared to MEP (RR: 0.40; CI: 0.16 – 0.99). The risk for antibiotic treatment was lower for MAB compared to MEP treated calves (RR = 0.38; CI: 0.17 – 0.88). The risk of shedding rotavirus was higher in MAB (RR = 1.38; CI: 1.10 – 1.81) calves. After multivariable analyses, hipometer weights (LSM ± SE) were 1.7 ± 0.8 kg greater on d 56 in MAB compared to MEP; however ADG was 0.04 ± 0.02 kg/d lower in MAB calves. Total health score, diarrhea days, average respiratory score, packed cell volume, and serum total protein were not affected by feeding anti-IL-10 egg antibodies. In summary, feeding anti-IL-10 antibodies was associated with increased fecal pH, reduced risk of respiratory disease later in the preweaning period, and decreased antibiotic usage despite higher rotavirus infection. These findings might be associated with improved mucosal immunity, enhanced host defenses, or reduced susceptibility and warrant further investigation.",,"['Raabis, S. M.', 'Ollivett, T. L.', 'Cook, M. E.', 'Sand, J. M.', 'McGuirk, S. M.']",,,,
,PMC,Integrative Physiology of Pneumonia,http://dx.doi.org/10.1152/physrev.00032.2017,PMC6088146,,,"Pneumonia is a type of acute lower respiratory infection that is common and severe. The outcome of lower respiratory infection is determined by the degrees to which immunity is protective and inflammation is damaging. Intercellular and interorgan signaling networks coordinate these actions to fight infection and protect the tissue. Cells residing in the lung initiate and steer these responses, with additional immunity effectors recruited from the bloodstream. Responses of extrapulmonary tissues, including the liver, bone marrow, and others, are essential to resistance and resilience. Responses in the lung and extrapulmonary organs can also be counterproductive and drive acute and chronic comorbidities after respiratory infection. This review discusses cell-specific and organ-specific roles in the integrated physiological response to acute lung infection, and the mechanisms by which intercellular and interorgan signaling contribute to host defense and healthy respiratory physiology or to acute lung injury, chronic pulmonary disease, and adverse extrapulmonary sequelae. Pneumonia should no longer be perceived as simply an acute infection of the lung. Pneumonia susceptibility reflects ongoing and poorly understood chronic conditions, and pneumonia results in diverse and often persistent deleterious consequences for multiple physiological systems.",,"['Quinton, Lee J.', 'Walkey, Allan J.', 'Mizgerd, Joseph P.']",,,,
,PMC,Infection Is Not Required for Mucoinflammatory Lung Disease in CFTR-Knockout Ferrets,http://dx.doi.org/10.1164/rccm.201708-1616OC,PMC5955060,,,"Rationale: Classical interpretation of cystic fibrosis (CF) lung disease pathogenesis suggests that infection initiates disease progression, leading to an exuberant inflammatory response, excessive mucus, and ultimately bronchiectasis. Although symptomatic antibiotic treatment controls lung infections early in disease, lifelong bacterial residence typically ensues. Processes that control the establishment of persistent bacteria in the CF lung, and the contribution of noninfectious components to disease pathogenesis, are poorly understood. Objectives: To evaluate whether continuous antibiotic therapy protects the CF lung from disease using a ferret model that rapidly acquires lethal bacterial lung infections in the absence of antibiotics. Methods: CFTR (cystic fibrosis transmembrane conductance regulator)–knockout ferrets were treated with three antibiotics from birth to several years of age and lung disease was followed by quantitative computed tomography, BAL, and histopathology. Lung disease was compared with CFTR-knockout ferrets treated symptomatically with antibiotics. Measurements and Main Results: Bronchiectasis was quantified from computed tomography images. BAL was evaluated for cellular differential and features of inflammatory cellular activation, bacteria, fungi, and quantitative proteomics. Semiquantitative histopathology was compared across experimental groups. We demonstrate that lifelong antibiotics can protect the CF ferret lung from infections for several years. Surprisingly, CF animals still developed hallmarks of structural bronchiectasis, neutrophil-mediated inflammation, and mucus accumulation, despite the lack of infection. Quantitative proteomics of BAL from CF and non-CF pairs demonstrated a mucoinflammatory signature in the CF lung dominated by Muc5B and neutrophil chemoattractants and products. Conclusions: These findings implicate mucoinflammatory processes in the CF lung as pathogenic in the absence of clinically apparent bacterial and fungal infections.",,"['Rosen, Bradley H.', 'Evans, T. Idil Apak', 'Moll, Shashanna R.', 'Gray, Jaimie S.', 'Liang, Bo', 'Sun, Xingshen', 'Zhang, Yulong', 'Jensen-Cody, Chandler W.', 'Swatek, Anthony M.', 'Zhou, Weihong', 'He, Nan', 'Rotti, Pavana G.', 'Tyler, Scott R.', 'Keiser, Nicholas W.', 'Anderson, Preston J.', 'Brooks, Leonard', 'Li, Yalan', 'Pope, R. Marshall', 'Rajput, Maheen', 'Hoffman, Eric A.', 'Wang, Kai', 'Harris, J. Kirk', 'Parekh, Kalpaj R.', 'Gibson-Corley, Katherine N.', 'Engelhardt, John F.']",,,,
,PMC,Excessive glutamate stimulation impairs ACE2 activity through ADAM17-mediated shedding in cultured cortical neurons,http://dx.doi.org/10.1007/s10571-018-0591-8,PMC6237671,,,"The excitotoxicity of glutamate plays an important role in the progression of various neurological disorders via participating in inflammation and neuronal damage. In this study, we identified the role of excessive glutamate stimulation in the modulation of angiotensin-converting enzyme type 2 (ACE2), a critical component in the compensatory axis of the renin-angiotensin system (RAS). In primary cultured cortical neurons, high concentration of glutamate (100 μM) significantly reduced the enzymatic activity of ACE2. The elevated activity of ADAM17, a member of the ‘A Disintegrin And Metalloprotease’ (ADAM) family, was found to contribute to this glutamate-induced ACE2 down-regulation. The decrease of ACE2 activity could be prevented by pre-treatment with antagonists targeting ionotropic glutamate receptors. In addition, the glutamate-induced decrease in ACE2 activity was significantly attenuated when the neurons were co-treated with MitoTEMPOL or blockers that target oxidative stress-mediated signaling pathway. In summary, our study reveals a strong relationship between excessive glutamate stimulation and ADAM17-mediated impairment in ACE2 activity, suggesting a possible cross-talk between glutamate-induced excitotoxicity and dysregulated RAS.",,"['Jiaxi, Xu', 'Sriramula, Srinivas', 'Lazartigues, Eric']",,,,
,PMC,Identification of H209 as Essential for pH 8-Triggered Receptor-Independent Syncytium Formation by S Protein of Mouse Hepatitis Virus A59,http://dx.doi.org/10.1128/JVI.00209-18,PMC5952161,,,"The spike glycoprotein (S) of murine coronavirus mouse hepatitis virus (MHV) strain A59 uses murine carcinoembryonic antigen-related cell adhesion molecule 1a as its receptor for cell entry, but S protein can also be triggered in the absence of receptor by pH 8.0 alone at 37°C. The mechanism by which conformational changes of this S glycoprotein can be triggered by pH 8.0 has not yet been determined. Here, we show that MHV-A59 S protein is triggered by pH 8.0 at 37°C to induce receptor-independent syncytium (RIS) formation on 293T cells, and that the conformational changes in S proteins triggered by pH 8.0 are very similar to those triggered by receptor binding. We systemically mutated each of 15 histidine residues in S protein and found that H209 is essential for pH 8.0-triggered RIS formation, while H179, H441, H643, and H759 also play important roles in this process. Replacement of H209 with Ala had no effect on receptor binding, but in murine 17Cl.1 cells mutant H209A MHV-A59 showed delayed growth kinetics and was readily outcompeted by wild-type virus when mixed together, indicating that the H209A mutation caused a defect in virus fitness. Finally, the H209A mutation significantly increased the thermostability of S protein in its prefusion conformation, which may raise the energy barrier for conformational change of S protein required for membrane fusion and lead to a decrease in virus fitness in cell culture. Thus, MHV-A59 may have evolved to lower the stability of its S protein in order to increase virus fitness. IMPORTANCE Enveloped viruses enter cells through fusion of viral and cellular membranes, and the process is mediated by interactions between viral envelope proteins and their host receptors. In the prefusion conformation, viral envelope proteins are metastable, and activation to the fusion conformation is tightly regulated, since premature activation would lead to loss of viral infectivity. The stability of viral envelope proteins greatly influences their activation and virus fitness. Here, we report that, similar to the A82V mutation in Ebola glycoprotein, in the S glycoprotein of murine coronavirus MHV-A59, the histidine residue at position of 209 significantly affects the thermal stability of the S protein, determines whether S protein can be activated at 37°C by either pH 8.0 alone or by receptor binding, and affects viral fitness in cell culture. Thus, the spike glycoprotein of MHV-A59 has evolved to retain histidine at position 209 to optimize virus fitness.",,"['Li, Pei', 'Shan, Yiwei', 'Zheng, Wangliang', 'Ou, Xiuyuan', 'Mi, Dan', 'Mu, Zhixia', 'Holmes, Kathryn V.', 'Qian, Zhaohui']",,,,
,PMC,Exacerbated Apoptosis of Cells Infected with Infectious Bursal Disease Virus upon Exposure to Interferon Alpha,http://dx.doi.org/10.1128/JVI.00364-18,PMC5952143,,,"Infectious bursal disease virus (IBDV) belongs to the Birnaviridae family and is the etiological agent of a highly contagious and immunosuppressive disease (IBD) that affects domestic chickens (Gallus gallus). IBD or Gumboro disease leads to high rates of morbidity and mortality of infected animals and is responsible for major economic losses to the poultry industry worldwide. IBD is characterized by a massive loss of IgM-bearing B lymphocytes and the destruction of the bursa of Fabricius. The molecular bases of IBDV pathogenicity are still poorly understood; nonetheless, an exacerbated cytokine immune response and B cell depletion due to apoptosis are considered main factors that contribute to the severity of the disease. Here we have studied the role of type I interferon (IFN) in IBDV infection. While IFN pretreatment confers protection against subsequent IBDV infection, the addition of IFN to infected cell cultures early after infection drives massive apoptotic cell death. Downregulation of double-stranded RNA (dsRNA)-dependent protein kinase (PKR), tumor necrosis factor alpha (TNF-α), or nuclear factor κB (NF-κB) expression drastically reduces the extent of apoptosis, indicating that they are critical proteins in the apoptotic response induced by IBDV upon treatment with IFN-α. Our results indicate that IBDV genomic dsRNA is a major viral factor that contributes to the triggering of apoptosis. These findings provide novel insights into the potential mechanisms of IBDV-induced immunosuppression and pathogenesis in chickens. IMPORTANCE IBDV infection represents an important threat to the poultry industry worldwide. IBDV-infected chickens develop severe immunosuppression, which renders them highly susceptible to secondary infections and unresponsive to vaccination against other pathogens. The early dysregulation of the innate immune response led by IBDV infection and the exacerbated apoptosis of B cells have been proposed as the main factors that contribute to virus-induced immunopathogenesis. Our work contributes for the first time to elucidating a potential mechanism driving the apoptotic death of IBDV-infected cells upon exposure to type I IFN. We provide solid evidence about the critical importance of PKR, TNF-α, and NF-κB in this phenomenon. The described mechanism could facilitate the early clearance of infected cells, thereby aiding in the amelioration of IBDV-induced pathogenesis, but it could also contribute to B cell depletion and immunosuppression. The balance between these two opposing effects might be dramatically affected by the genetic backgrounds of both the host and the infecting virus strain.",,"['Cubas-Gaona, Liliana L.', 'Diaz-Beneitez, Elisabet', 'Ciscar, Marina', 'Rodríguez, José F.', 'Rodríguez, Dolores']",,,,
,PMC,Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility,http://dx.doi.org/10.1073/pnas.1802879115,PMC5984533,,,"Porcine deltacoronavirus (PDCoV), identified in 2012, is a common enteropathogen of swine with worldwide distribution. The source and evolutionary history of this virus is, however, unknown. PDCoV belongs to the Deltacoronavirus genus that comprises predominantly avian CoV. Phylogenetic analysis suggests that PDCoV originated relatively recently from a host-switching event between birds and mammals. Insight into receptor engagement by PDCoV may shed light into such an exceptional phenomenon. Here we report that PDCoV employs host aminopeptidase N (APN) as an entry receptor and interacts with APN via domain B of its spike (S) protein. Infection of porcine cells with PDCoV was drastically reduced by APN knockout and rescued after reconstitution of APN expression. In addition, we observed that PDCoV efficiently infects cells of unusual broad species range, including human and chicken. Accordingly, PDCoV S was found to target the phylogenetically conserved catalytic domain of APN. Moreover, transient expression of porcine, feline, human, and chicken APN renders cells susceptible to PDCoV infection. Binding of PDCoV to an interspecies conserved site on APN may facilitate direct transmission of PDCoV to nonreservoir species, including humans, potentially reflecting the mechanism that enabled a virus, ancestral to PDCoV, to breach the species barrier between birds and mammals. The APN cell surface protein is also used by several members of the Alphacoronavirus genus. Hence, our data constitute the second identification of CoVs from different genera that use the same receptor, implying that CoV receptor selection is subjected to specific restrictions that are still poorly understood.",,"['Li, Wentao', 'Hulswit, Ruben J. G.', 'Kenney, Scott P.', 'Widjaja, Ivy', 'Jung, Kwonil', 'Alhamo, Moyasar A.', 'van Dieren, Brenda', 'van Kuppeveld, Frank J. M.', 'Saif, Linda J.', 'Bosch, Berend-Jan']",,,,
,PMC,Successful treatment of suckling Red Angus calves for bovine respiratory disease is not associated with increased mean pulmonary arterial pressures at weaning,http://dx.doi.org/10.1093/jas/sky189,PMC6095343,,,"The purposes of this study were to determine if the successful treatment of bovine respiratory disease (BRD) in suckling calves was associated with a long-term increase in mean pulmonary arterial pressure (mPAP) and, to screen for associations between blood leukogram variables and mPAP. A cohort of Red Angus calves (n = 74) were followed from birth to weaning at an altitude of 975 m. Calves were weaned at 172 ± 14 d when their mPAP was measured and whole blood collected. Thirty calves that had been treated for BRD (34 to 45 d prior) and 30 calves that had not required treatment for BRD were sampled. Treatment for BRD had no effect on mPAP (P = 0.37). Mean mPAP was 48 ± 8 mm Hg (± SD) with a minimum of 34 mm Hg and a maximum at 69 mm Hg. Weaning weight and sex tended to be associated with mPAP, but they explained just 5% of the variation in mPAP (P = 0.08; Adj. r(2) = 0.05). Fibrinogen (P = 0.008) and absolute lymphocyte count (P = 0.06) were negatively associated with mPAP, whereas absolute monocyte count was positively associated with mPAP (P = 0.01). The findings of this study suggest that pre-weaning treatment for BRD does not increase a calves’ post-weaning risk of congestive right heart failure. Further, components of the immune and acute phase response system may play a role in the development and progression of pulmonary hypertension.",,"['Neary, Joseph M', 'Church, Dee', 'Reeves, Nathan', 'Rathmann, Ryan J']",,,,
,PMC,Using Clinical Research Networks to Assess Severity of an Emerging Influenza Pandemic,http://dx.doi.org/10.1093/cid/ciy088,PMC6248856,,,"BACKGROUND: Early clinical severity assessments during the 2009 influenza A H1N1 pandemic (pH1N1) overestimated clinical severity due to selection bias and other factors. We retrospectively investigated how to use data from the International Network for Strategic Initiatives in Global HIV Trials, a global clinical influenza research network, to make more accurate case fatality ratio (CFR) estimates early in a future pandemic, an essential part of pandemic response. METHODS: We estimated the CFR of medically attended influenza (CFR(MA)) as the product of probability of hospitalization given confirmed outpatient influenza and the probability of death given hospitalization with confirmed influenza for the pandemic (2009–2011) and post-pandemic (2012–2015) periods. We used literature survey results on health-seeking behavior to convert that estimate to CFR among all infected persons (CFR(AR)). RESULTS: During the pandemic period, 5.0% (3.1%–6.9%) of 561 pH1N1-positive outpatients were hospitalized. Of 282 pH1N1-positive inpatients, 8.5% (5.7%–12.6%) died. CFR(MA) for pH1N1 was 0.4% (0.2%–0.6%) in the pandemic period 2009–2011 but declined 5-fold in young adults during the post-pandemic period compared to the level of seasonal influenza in the post-pandemic period 2012–2015. CFR for influenza-negative patients did not change over time. We estimated the 2009 pandemic CFR(AR) to be 0.025%, 16-fold lower than CFR(MA). CONCLUSIONS: Data from a clinical research network yielded accurate pandemic severity estimates, including increased severity among younger people. Going forward, clinical research networks with a global presence and standardized protocols would substantially aid rapid assessment of clinical severity. CLINICAL TRIALS REGISTRATION: NCT01056354 and NCT010561.",,"['Simonsen, Lone', 'Higgs, Elizabeth', 'Taylor, Robert J', 'Wentworth, Deborah', 'Cozzi-Lepri, Al', 'Pett, Sarah', 'Dwyer, Dominic E', 'Davey, Richard', 'Lynfield, Ruth', 'Losso, Marcelo', 'Morales, Kathleen', 'Glesby, Marshall J', 'Weckx, Jozef', 'Carey, Dianne', 'Lane, Cliff', 'Lundgren, Jens', None]",,,,
,PMC,Autoimmune phenotypes in schizophrenia reveal novel treatment targets,http://dx.doi.org/10.1016/j.pharmthera.2018.05.005,PMC6097895,,,"Typical and atypical antipsychotics are the first-line treatments for schizophrenia, but these classes of drugs are not universally effective, and they can have serious side effects that impact compliance. Antipsychotic drugs generally target the dopamine pathways with some variation. As research of schizophrenia pathophysiology has shifted away from a strictly dopamine-centric focus, the development of new pharmacotherapies has waned. A field of inquiry with centuries-old roots is gaining traction in psychiatric research circles and may represent a new frontier for drug discovery in schizophrenia. At the forefront of this investigative effort is the immune system and its many components, pathways and phenotypes, which are now known to actively engage the brain. Studies in schizophrenia reveal an intricate association of environmentally-driven immune activation in concert with a disrupted genetic template. A consistent conduit through this gene-environmental milieu is the gut-brain axis, which when dysregulated can generate pathological autoimmunity. In this review, we present epidemiological and biochemical evidence in support of an autoimmune component in schizophrenia and depict gut processes and a dysbiotic microbiome as a source and perpetuator of autoimmune dysfunction in the brain. Within this framework, we review the role of infectious agents, inflammation, gut dysbioses and autoantibody propagation on CNS pathologies such as neurotransmitter receptor hypofunction and complement pathway-mediated synaptic pruning. We then review the new pharmacotherapeutic horizon and novel agents directed to impact these pathological conditions. At the core of this discourse is the understanding that schizophrenia is etiologically and pathophysiologically heterogeneous and thus its treatment requires individualized attention with disease state variants diagnosed with objective biomarkers.",,"['Severance, Emily G.', 'Dickerson, Faith B.', 'Yolken, Robert H.']",,,,
,PMC,Factors Associated With Prolonged Viral Shedding in Patients With Avian Influenza A(H7N9) Virus Infection,http://dx.doi.org/10.1093/infdis/jiy115,PMC6679685,,,"BACKGROUND. Data are limited on the impact of neuraminidase inhibitor (NAI) treatment on avian influenza A(H7N9) virus RNA shedding. METHODS. In this multicenter, retrospective study, data were collected from adults hospitalized with A(H7N9) infection during 2013–2017 in China. We compared clinical features and A(H7N9) shedding among patients with different NAI doses and combination therapies and evaluated factors associated with A(H7N9) shedding, using Cox proportional hazards regression. RESULTS. Among 478 patients, the median age was 56 years, 71% were male, and 37% died. The median time from illness onset to NAI treatment initiation was 8 days (interquartile range [IQR], 6–10 days), and the median duration of A(H7N9) RNA detection from onset was 15.5 days (IQR, 12–20 days). A(H7N9) RNA shedding was shorter in survivors than in patients who died (P < .001). Corticosteroid administration (hazard ratio [HR], 0.62 [95% confidence interval {CI}, .50-.77]) and delayed NAI treatment (HR, 0.90 [95% CI, .91-.96]) were independent risk factors for prolonged A(H7N9) shedding. There was no significant difference in A(H7N9) shedding duration between NAI combination treatment and monotherapy (P = .65) or between standard-dose and double-dose oseltamivir treatment (P = .70). CONCLUSIONS. Corticosteroid therapy and delayed NAI treatment were associated with prolonged A(H7N9) RNA shedding. NAI combination therapy and double-dose oseltamivir treatment were not associated with a reduced A(H7N9) shedding duration as compared to standard-dose oseltamivir.",,"['Wang, Yeming', 'Guo, Qiang', 'Yan, Zheng', 'Zhou, Daming', 'Zhang, Wei', 'Zhou, Shujun', 'Li, Yu-Ping', 'Yuan, Jing', 'Uyeki, Timothy M.', 'Shen, Xinghua', 'Wu, Wenjuan', 'Zhao, Hui', 'Wu, Yun-Fu', 'Shang, Jia', 'He, Zhengguang', 'Yang, Yi', 'Zhao, Hongsheng', 'Hong, Yongqing', 'Zhang, Zehua', 'Wu, Min', 'Wei, Tiemin', 'Deng, Xilong', 'Deng, Yijun', 'Cai, Li-hua', 'Lu, Weihua', 'Shu, Hongmei', 'Zhang, Lin', 'Luo, Hong', 'Zhou, Ying', 'Weng, Heng', 'Song, Keyi', 'Yao, Li', 'Jiang, Mingguang', 'Zhao, Boliang', 'Chi, Ruibin', 'Guo, Boqi', 'Fu, Lin', 'Yu, Long', 'Min, Haiyan', 'Chen, Pu', 'Chen, Shuifang', 'Hong, Liang', 'Mao, Wei', 'Huang, Xiaoping', 'Gu, Lijun', 'Li, Hui', 'Wang, Chen', 'Cao, Bin', None]",,,,
,PMC,An overview of the National Microbiology Laboratory emergency management program,http://dx.doi.org/10.14745/ccdr.v44i05a02,PMC6449121,,,"The National Microbiology Laboratory (NML) emergency management program was developed after the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak to provide a framework for the responses to public health events. The program comprises three components (Site response, Continuity and Site support) that have adopted the Incident Command System (ICS) as their management structure and follows the four phases of emergency management. All program components have extensive competency-based training for staff and exercise plans. The emergency management program ensures quality and continuous improvement through its certification in International Organization for Standardization (ISO) 9001 and structured review processes. This means that the Operations Centre can be activated and working at optimum capacity with highly trained and experienced staff within an hour of receiving notice to begin a response. The NML can also send mobile laboratories to aid Canadian or international efforts to address outbreaks or bioterrorism events.",,"['Marcino, D', 'Gordon, K']",,,,
,PMC,Fifteen years post-SARS: Key milestones in Canada’s public health emergency response,http://dx.doi.org/10.14745/ccdr.v44i05a01,PMC6449094,,,"This year marks the 15th anniversary of Severe Acute Respiratory Syndrome (SARS) in Canada and the 100th anniversary of the 1918 Spanish influenza pandemic. These, and other recent public health events, provide an opportunity for us to review and reflect on the evolution of Canada’s public health emergency response over the past 15 years—from SARS, to the 2009 H1N1 pandemic influenza, to Ebola virus and Zika virus disease. Key lessons have been learned and milestones achieved that have shaped and sharpened our response approach and structures. While SARS was a wake-up-call to strengthen infection prevention and control capacity in health care settings and led to the formation of the Public Health Agency of Canada, it also strengthened our Federal/Provincial/Territorial (FPT) senior-level governance and led to agreements for pan-Canadian mutual aid and infectious disease information sharing. As well, our collective public health laboratory capacity has been strengthened through ongoing response and sharing of advanced diagnostics and research. As we move forward, it will be important to explore the design of scalable or modular emergency response strategies and structures that are socio-culturally appropriate and employ evidence-based strategic risk communications that continue to be critical, especially given the volume and spread of misinformation. With the current global reality, we must recognize that public health threats that go unchecked anywhere in the world have the potential to very rapidly become a public health threat in Canada. We need to build, maintain and share our best public health practices globally, for we neglect these at our peril.",,"Tam, T",,,,
,PMC,Neutrophils are essential for induction of vaccine-like effects by antiviral monoclonal antibody immunotherapies,http://dx.doi.org/10.1172/jci.insight.97339,PMC6012508,,,"Using a mouse retroviral model, we have shown that mAb-based immunotherapy can induce life-long endogenous protective immunity (vaccine-like effects). This observation has potentially important consequences for treating life-threatening human viral infections. Here, we investigated the role of neutrophils in this effect. Neutrophils are innate immunity effector cells with well-established microbe-killing activities that are rapidly mobilized upon infection. They are also emerging as orchestrators of innate and adaptive immunities. However, their immunomodulatory activity during antiviral mAb immunotherapies has never been studied. Our data reveal that neutrophils have an essential role in immunotherapy-induced immune protection of infected mice. Unexpectedly, neutrophils have a limited effect in controlling viral propagation upon passive immunotherapy administration, which is mostly mediated by NK cells. Instead, neutrophils operate as essential inducers of a potent host humoral antiviral response. Thus, neutrophils play an unexpected key role in protective immunity induction by antiviral mAbs. Our work opens approaches to improve antiviral immunotherapies, as it suggests that preserving neutrophil functions and counts might be required for achieving mAb-induced protective immunity.",,"['Naranjo-Gomez, Mar', 'Lambour, Jennifer', 'Piechaczyk, Marc', 'Pelegrin, Mireia']",,,,
,PMC,Global site-specific analysis of glycoprotein N-glycan processing,http://dx.doi.org/10.1038/nprot.2018.024,PMC5941933,,,"N-glycans contribute to the folding, stability and functions of the proteins they decorate. They are produced by transfer of the glycan precursor to the sequon Asn-X-Thr/Ser, followed by enzymatic trimming to a high mannose-type core and sequential addition of monosaccharides to generate complex-type and hybrid glycans. This process, mediated by the concerted action of multiple enzymes, produces a mixture of related glycoforms at each glycosite, making analysis of glycosylation difficult. To address this analytical challenge we developed a robust semi-quantitative MS-based method that determines the degree of glycan occupancy at each glycosite, and the proportion of N-glycans processed from high mannose type to complex type. It is applicable to virtually any glycoprotein, and a complete analysis can be conducted with 30 μg of protein or less. Here we provide a detailed description of the method that includes procedures for (1) proteolytic digestion of glycoprotein(s) with specific and non-specific proteases; (2) denaturation of proteases by heating; (3) sequential treatment of the glycopeptide mixture with two endoglycosidases, Endo H and PNGase F, to create unique mass signatures for the three glycosylation states; (4) LC-MS/MS analysis; (5) data analysis for identification and quantitation of peptides for the three glycosylation states. Full coverage of site-specific glycosylation of glycoproteins is achieved with up to thousands of high-confidence spectra hits for each glycosite. The protocol can be performed by an experienced technician or student/post-doc with basic skills for proteomics experiments and takes approximately 7 days to complete.",,"['Cao, Liwei', 'Diedrich, Jolene K.', 'Ma, Yuanhui', 'Wang, Nianshuang', 'Pauthner, Matthias', 'Park, Sung-Kyu Robin', 'Delahunty, Claire M.', 'McLellan, Jason S.', 'Burton, Dennis R.', 'Yates, John R.', 'Paulson, James C.']",,,,
,PMC,Advances in Meningeal Immunity,http://dx.doi.org/10.1016/j.molmed.2018.04.003,PMC6044730,,,"The central nervous system (CNS) is an immunologically specialized tissue protected by a blood-brain barrier. The CNS parenchyma is enveloped by a series of overlapping membranes that are collectively referred to as the meninges. The meninges provide an additional CNS barrier, harbor a diverse array of resident immune cells, and serve as a crucial interface with the periphery. Recent studies have significantly advanced our understanding of meningeal immunity, demonstrating how a complex immune landscape influences CNS functions under steady state and inflammatory conditions. The location and activation state of meningeal immune cells can profoundly influence CNS homeostasis and contribute to neurological disorders, but these cells are also well equipped to protect the CNS from pathogens. In this review, we discuss advances in our understanding of the meningeal immune repertoire and provide insights into how this CNS barrier operates immunologically under conditions ranging from neurocognition to inflammatory diseases.",,"['Rua, Rejane', 'McGavern, Dorian B.']",,,,
,PMC,Validation of a radioimmunoassay of serum trypsin-like immunoreactivity in ferrets,http://dx.doi.org/10.1177/1040638718774387,PMC6343499,,,"Measurement of serum trypsin-like immunoreactivity (TLI) is used to assess exocrine pancreatic function in dogs and cats. Ferrets (Mustela putorius furo) serve as valuable animal models for human diseases such as cystic fibrosis and other pulmonary diseases, and may be a useful model of other diseases including pancreatitis. We developed and analytically validated a competitive radioimmunoassay (RIA) for measurement of TLI in ferret serum by determination of analytical sensitivity, assay linearity, accuracy of spiking recovery, precision, and reproducibility. Analytical sensitivity of the assay was 0.55 μg/L. Observed-to-expected (O/E) ratio for dilutional parallelism was 90.2–127.9% (mean: 108.1 ± 11.9%). The O/E ratio for spiking recovery was 94.5–113.0% (mean: 103.9 ± 7.2%). The intra- and inter-assay coefficients of variation (CVs) were 2.7–5.7% and 3.5–8.2%, respectively. The reference interval (RI) for serum TLI derived from 31 healthy ferrets was 28–115 μg/L; the 90% confidence interval for the lower and upper limits of the RI were 10.0–32.1 μg/L and 103–126 μg/L, respectively. This TLI RIA is analytically sensitive, sufficiently linear, accurate, precise, and reproducible for the measurement of TLI in ferret serum samples.",,"['Bridges, Cory S.', 'Miller, Pamela S.', 'Lidbury, Jonathan A.', 'Suchodolski, Jan S.', 'Yi, Yaling', 'Engelhardt, John F.', 'Steiner, Jörg M.']",,,,
,PMC,Prevalence of Ear Infections in First Year Children of Primary Schools in A Western Ugandan Community,,PMC6959216,,,"Ear infections in the United Kingdom were reported at a prevalence of 90% in children aged 0–6 years peaking at six years, the commonest age for Ugandan children to start primary school. This study was done to determine prevalence of ear infections in primary one children in Mbarara district, identify commonest ear infections, the causative pathogens isolated and their antibiograms and comparing the prevalence of ear infection in urban and rural schools. A cross sectional study was carried out among three urban day schools and three rural day schools randomly chosen in Mbarara district. History was taken using a data collection form and examinations were done using an otoscope. All pus swabs from infected ears were inoculated on Blood agar, Chocolate agar, MacConkey Agar plates before smears for Gram staining were made. Identification of the pathogen was through biochemical tests and API system. Sensitivity tests to antibiotics were set on Mueller Hinton Agar using the disc diffusion technique of Kirby-Bauer. Otoscopy was done on 600 children, 8.0 %( 48) showed signs of ear infections. The commonest ear infection was otitis externa. Staphylococcus aureus species showed the highest prevalence with 75% (6). Staphylococcus aureus species showed 100% sensitivity to gentamicin, 80% sensitivity to ciproflaxin. Serratia marcencens also showed 100% sensitivity to ciproflaxin, The prevalence of ear infection was 8.0% among children in primary one in Mbarara district in a cross sectional study.",,"['Kisembo, P', 'Mugwanya, F', 'Atumanya, P', 'Othin, M', 'Oworinawe, R', 'Kagimu, B', 'Kisakye, A', 'Bagambe, F']",,,,
,PMC,Emerging and re-emerging infectious disease in otorhinolaryngology,http://dx.doi.org/10.14639/0392-100X-suppl.1-38-2018,PMC6056203,,,"Emerging and re-emerging infectious disease in otorhinolaryngology (ENT) are an area of growing epidemiological and clinical interest. The aim of this section is to comprehensively report on the epidemiology of key infectious disease in otorhinolaryngology, reporting on their burden at the national and international level, expanding of the need of promoting and implementing preventive interventions, and the rationale of applying evidence-based, effective and cost- effective diagnostic, curative and preventive approaches. In particular, we focus on i) ENT viral infections (HIV, Epstein-Barr virus, Human Papilloma virus), retrieving the available evidence on their oncogenic potential; ii) typical and atypical mycobacteria infections; iii) non-specific granulomatous lymphadenopathy; iv) emerging paediatric ENT infectious diseases and the prevention of their complications; v) the growing burden of antimicrobial resistance in ENT and the strategies for its control in different clinical settings. We conclude by outlining knowledge gaps and action needed in ENT infectious diseases research and clinical practice and we make references to economic analysis in the field of ENT infectious diseases prevention and care.",,"['SCASSO, F.', 'FERRARI, G.', 'DE VINCENTIIS, G.C.', 'AROSIO, A.', 'BOTTERO, S.', 'CARRETTI, M.', 'CIARDO, A.', 'COCUZZA, S.', 'COLOMBO, A.', 'CONTI, B.', 'CORDONE, A.', 'DE CICCIO, M.', 'DELEHAYE, E.', 'DELLA VECCHIA, L.', 'DE MACINA, I.', 'DENTONE, C.', 'DI MAURO, P.', 'DORATI, R.', 'FAZIO, R.', 'FERRARI, A.', 'FERREA, G.', 'GIANNANTONIO, S.', 'GENTA, I.', 'GIULIANI, M.', 'LUCIDI, D.', 'MAIOLINO, L.', 'MARINI, G.', 'MARSELLA, P.', 'MEUCCI, D.', 'MODENA, T.', 'MONTEMURRI, B.', 'ODONE, A.', 'PALMA, S.', 'PANATTA, M.L.', 'PIEMONTE, M.', 'PISANI, P.', 'PISANI, S.', 'PRIOGLIO, L.', 'SCORPECCI, A.', 'SCOTTO DI SANTILLO, L.', 'SERRA, A.', 'SIGNORELLI, C.', 'SITZIA, E.', 'TROPIANO, M.L.', 'TROZZI, M.', 'TUCCI, F.M.', 'VEZZOSI, L.', 'VIAGGI, B.']",,,,
,PMC,Randomized phase 2 trial of monthly vitamin D to prevent respiratory complications in children with sickle cell disease,http://dx.doi.org/10.1182/bloodadvances.2017013979,PMC5941998,,,"In sickle cell disease, respiratory infection and asthma may lead to respiratory complications that are a leading cause of morbidity and mortality. Vitamin D has anti-infective and immunomodulatory effects that may decrease the risk for respiratory infections, asthma, and acute chest syndrome. We conducted a randomized double-blind active-controlled clinical trial to determine whether monthly oral vitamin D(3) can reduce the rate of respiratory events in children with sickle cell disease. Seventy sickle cell subjects, ages 3-20 years, with baseline records of respiratory events over 1 year before randomization, underwent screening. Sixty-two subjects with 25-hydroxyvitamin D levels of 5-60 ng/mL were randomly assigned to oral vitamin D(3) (100 000 IU or 12 000 IU, n = 31 each) under observed administration once monthly for 2 years. The primary outcome was the annual rate of respiratory events (respiratory infection, asthma exacerbation, or acute chest syndrome) ascertained by the use of a validated questionnaire administered biweekly. Analysis included 62 children (mean age of 9.9 years, 52% female, and predominantly with homozygous HbS disease [87%]) with mean baseline 25-hydroxyvitamin D of 14.3 ng/mL. The annual rates of respiratory events at baseline and intervention years 1 and 2 were 4.34 ± 0.35, 4.28 ± 0.36, and 1.49 ± 0.37 (high dose) and 3.91 ± 0.35, 3.34 ± 0.37, and 1.54 ± 0.37 (standard dose), respectively. In pediatric patients with sickle cell disease, 2-year monthly oral vitamin D(3) was associated with a >50% reduction in the rate of respiratory illness during the second year (P = .0005), with similar decreases associated with high- and standard-dose treatment. This trial was registered at www.clinicaltrials.gov as #NCT01443728.",,"['Lee, Margaret T.', 'Kattan, Meyer', 'Fennoy, Ilene', 'Arpadi, Stephen M.', 'Miller, Rachel L.', 'Cremers, Serge', 'McMahon, Donald J.', 'Nieves, Jeri W.', 'Brittenham, Gary M.']",,,,
,PMC,Health Care System and Pharmacy Practice in Hong Kong,,PMC5931074,,,,,"Lee, Chui Ping",,,,
,PMC,Nebulization of Single-Chain Tissue-Type and Single-Chain Urokinase Plasminogen Activator for Treatment of Inhalational Smoke-Induced Acute Lung Injury,http://dx.doi.org/10.1016/j.jddst.2018.04.013,PMC6095669,,,"Single-chain tissue-type plasminogen activator (sctPA) and single-chain urokinase plasminogen activator (scuPA) have attracted interest as enzymes for the treatment of inhalational smoke-induced acute lung injury (ISALI). In this study, the pulmonary delivery of commercial human sctPA and lyophilized scuPA and their reconstituted solution forms were demonstrated using vibrating mesh nebulizers (Aeroneb® Pro (active) and EZ Breathe® (passive)). Both the Aeroneb® Pro and EZ Breathe® vibrating mesh nebulizers produced atomized droplets of protein solution of similar size of less than about 5 μm, which is appropriate for pulmonary delivery. Enzymatic activities of scuPA and of sctPA were determined after nebulization and both remained stable (88.0% and 93.9%). Additionally, the enzymatic activities of sctPA and tcuPA were not significantly affected by excipients, lyophilization or reconstitution conditions. The results of these studies support further development of inhaled formulations of fibrinolysins for delivery to the lungs following smoke-induced acute pulmonary injury.",,"['Surasarang, Soraya Hengsawas', 'Sahakijpijarn, Sawittree', 'Florova, Galina', 'Komissarov, Andrey A.', 'Nelson, Christina L.', 'Perenlei, Enkhbaatar', 'Fukuda, Satoshi', 'Wolfson, Marla R.', 'Shaffer, Thomas H.', 'Idell, Steven', 'Williams, Robert O.']",,,,
,PMC,Importance of Neutralizing Monoclonal Antibodies Targeting Multiple Antigenic Sites on the Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein To Avoid Neutralization Escape,http://dx.doi.org/10.1128/JVI.02002-17,PMC5923077,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with ∼35% mortality. The potential for a future pandemic originating from animal reservoirs or health care-associated events is a major public health concern. There are no vaccines or therapeutic agents currently available for MERS-CoV. Using a probe-based single B cell cloning strategy, we have identified and characterized multiple neutralizing monoclonal antibodies (MAbs) specifically binding to the receptor-binding domain (RBD) or S1 (non-RBD) regions from a convalescent MERS-CoV-infected patient and from immunized rhesus macaques. RBD-specific MAbs tended to have greater neutralizing potency than non-RBD S1-specific MAbs. Six RBD-specific and five S1-specific MAbs could be sorted into four RBD and three non-RBD distinct binding patterns, based on competition assays, mapping neutralization escape variants, and structural analysis. We determined cocrystal structures for two MAbs targeting the RBD from different angles and show they can bind the RBD only in the “out” position. We then showed that selected RBD-specific, non-RBD S1-specific, and S2-specific MAbs given prophylactically prevented MERS-CoV replication in lungs and protected mice from lethal challenge. Importantly, combining RBD- and non-RBD MAbs delayed the emergence of escape mutations in a cell-based virus escape assay. These studies identify MAbs targeting different antigenic sites on S that will be useful for defining mechanisms of MERS-CoV neutralization and for developing more effective interventions to prevent or treat MERS-CoV infections. IMPORTANCE MERS-CoV causes a highly lethal respiratory infection for which no vaccines or antiviral therapeutic options are currently available. Based on continuing exposure from established reservoirs in dromedary camels and bats, transmission of MERS-CoV into humans and future outbreaks are expected. Using structurally defined probes for the MERS-CoV spike glycoprotein (S), the target for neutralizing antibodies, single B cells were sorted from a convalescent human and immunized nonhuman primates (NHPs). MAbs produced from paired immunoglobulin gene sequences were mapped to multiple epitopes within and outside the receptor-binding domain (RBD) and protected against lethal MERS infection in a murine model following passive immunization. Importantly, combining MAbs targeting distinct epitopes prevented viral neutralization escape from RBD-directed MAbs. These data suggest that antibody responses to multiple domains on CoV spike protein may improve immunity and will guide future vaccine and therapeutic development efforts.",,"['Wang, Lingshu', 'Shi, Wei', 'Chappell, James D.', 'Joyce, M. Gordon', 'Zhang, Yi', 'Kanekiyo, Masaru', 'Becker, Michelle M.', 'van Doremalen, Neeltje', 'Fischer, Robert', 'Wang, Nianshuang', 'Corbett, Kizzmekia S.', 'Choe, Misook', 'Mason, Rosemarie D.', 'Van Galen, Joseph G.', 'Zhou, Tongqing', 'Saunders, Kevin O.', 'Tatti, Kathleen M.', 'Haynes, Lia M.', 'Kwong, Peter D.', 'Modjarrad, Kayvon', 'Kong, Wing-Pui', 'McLellan, Jason S.', 'Denison, Mark R.', 'Munster, Vincent J.', 'Mascola, John R.', 'Graham, Barney S.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00470-18,PMC5923064,,,,,,,,,
,PMC,Lectin Affinity Plasmapheresis for Middle East Respiratory Syndrome-Coronavirus and Marburg Virus Glycoprotein Elimination,http://dx.doi.org/10.1159/000487224,PMC6008873,,,"BACKGROUND/AIMS: Middle East respiratory syndrome coronavirus (MERS-CoV) and Marburg virus (MARV) are among the World Health Organization's top 8 emerging pathogens. Both zoonoses share nonspecific early symptoms, a high lethality rate, and a reduced number of specific treatment options. Therefore, we evaluated extracorporeal virus and glycoprotein (GP) elimination by lectin affinity plasmapheresis (LAP). METHODS: For both MERS-CoV (pseudovirus) as well as MARV (GPs), 4 LAP devices (Mini Hemopurifiers, Aethlon Medical, San Diego, CA, USA) and 4 negative controls were tested. Samples were collected every 30 min and analyzed for reduction in virus infectivity by a flow cytometry-based infectivity assay (MERS-CoV) and in soluble GP content (MARV) by an immunoassay. RESULTS: The experiments show a time-dependent clearance of MERS-CoV of up to 80% within 3 h (pseudovirus). Up to 70% of MARV-soluble GPs were eliminated at the same time. Substantial saturation of the binding resins was detected within the first treatment hour. CONCLUSION: MERS-CoV (pseudovirus) and MARV soluble GPs are eliminated by LAP in vitro. Considering the high lethality and missing established treatment options, LAP should be evaluated in vivo. Especially early initiation, continuous therapy, and timed cartridge exchanges could be of importance.",,"['Koch, Benjamin', 'Schult-Dietrich, Patricia', 'Büttner, Stefan', 'Dilmaghani, Bijan', 'Lohmann, Dario', 'Baer, Patrick C.', 'Dietrich, Ursula', 'Geiger, Helmut']",,,,
,PMC,Chronic Cough Related to Acute Viral Bronchiolitis in Children: CHEST Expert Panel Report,http://dx.doi.org/10.1016/j.chest.2018.04.019,PMC6689073,,,"BACKGROUND: Acute bronchiolitis is common in young children, and some children develop chronic cough after their bronchiolitis. We thus undertook systematic reviews based on key questions (KQs) using the PICO (Population, Intervention, Comparison, Outcome) format. The KQs were: Among children with chronic cough (> 4 weeks) after acute viral bronchiolitis, how effective are the following interventions in improving the resolution of cough?: (1) Antibiotics. If so what type and for how long? (2) Asthma medications (inhaled steroids, beta(2) agonist, montelukast); and (3) Inhaled osmotic agents like hypertonic saline? METHODS: We used the CHEST expert cough panel’s protocol and the American College of Chest Physicians (CHEST) methodological guidelines and GRADE framework. Data from the systematic reviews in conjunction with patients’ values and preferences and the clinical context were used to form these suggestions. Delphi methodology was used to obtain consensus. RESULTS: Several studies and systematic reviews on the efficacy of the three types of interventions listed in the introduction were found but no data were relevant to our KQs. Thus, no recommendations on using the interventions above could be formulated. CONCLUSIONS: The panel made several consensus-based suggestions and identified directions for future studies to advance the field of managing chronic cough post-acute bronchiolitis in children.",,"['Chang, Anne B.', 'Oppenheimer, John J.', 'Rubin, Bruce K.', 'Weinberger, Miles', 'Irwin, Richard S.', None]",,,,
,PMC,"Molecular Cloning and Identification of the 2′–5′ Oligoadenylate Synthetase 2 Gene in Chinese Domestic Pigs Through Bioinformatics Analysis, and Determination of Its Antiviral Activity Against Porcine Reproductive and Respiratory Syndrome Virus Infection",http://dx.doi.org/10.1007/s12088-018-0731-3,PMC6023816,,,"An interferon-mediated antiviral protein, 2′–5′ oligoadenylate synthetase 2, plays an important role in the antiviral response of interferons. In this study, 2′–5′ oligoadenylate synthetase 2 genes were cloned from Chinese domestic pigs. Bioinformatics analysis revealed that the 2024-bp long open reading fame encodes 707 amino acids. There are two conserved regions in this protein: the nucleotidyltransferase domain, and the 2′–5′ oligoadenylate synthetase domain (OAS). Genetic evolution analysis showed that the 2′–5′ oligoadenylate synthetase 2 gene in domestic pigs is closely related to that of cattle. There are multiple antigenic sites, no signal peptide, and no transmembrane region in the gene, which is predicted to be a hydrophilic protein. Secondary structures were found to be mainly alpha helix-based; its tertiary structure is close to that of humans and cattle, but not that of mice. Tissue distribution results indicated that this protein is distributed in multiple organs, with high distribution in the liver; it is mainly localized in the cytoplasm. PRRSV infection, interferon-beta, and Poly(I: C) treatment all promoted 2′–5′ oligoadenylate synthetase 2 gene expression. Overexpression and RNA silencing of porcine OAS2 inhibited and promoted PRRSV replication in cells, respectively. The inhibitory effect of porcine OAS2 was mainly dependent on RNase L, similar to what was predicted. This study has laid the foundation for future antiviral studies in pig, and provided a new way of preventing and treating PRRSV in the future.",,"['Wang, Ruining', 'Ma, Hongfang', 'Kang, Yinfeng', 'Li, Cunfa', 'Li, Huawei', 'Zhang, Erqin', 'Ji, Pengchao', 'He, Jian', 'Zhao, Mengmeng']",,,,
,PMC,Rotation-Activated and Cooperative Zipping Characterize Class I Viral Fusion Protein Dynamics,http://dx.doi.org/10.1016/j.bpj.2018.03.005,PMC5937144,,,"Class I viral fusion proteins are α-helical proteins that facilitate membrane fusion between viral and host membranes through large conformational transitions. Although prefusion and postfusion crystal structures have been solved for many of these proteins, details about how they transition between these states have remained elusive. This work presents the first, to our knowledge, computational survey of transitions between pre- and postfusion configurations for several class I viral fusion proteins using structure-based models to analyze their dynamics. As suggested by their structural similarities, all proteins share common mechanistic features during their transitions that can be characterized by a diffusive rotational search followed by cooperative N- and C-terminal zipping. Instead of predicting a stable spring-loaded intermediate, our model suggests that helical bundle formation is mediated by N- and C-terminal interactions late in the transition. Shared transition features suggest a global mechanism in which fusion is activated by slow protein-core rotation.",,"['Eddy, Nathanial R.', 'Onuchic, José N.']",,,,
,PMC,Characterization of a Vesivirus Associated with an Outbreak of Acute Hemorrhagic Gastroenteritis in Domestic Dogs,http://dx.doi.org/10.1128/JCM.01951-17,PMC5925730,,,"Four of eleven affected dogs died despite aggressive treatment during a 2015 focal outbreak of hemorrhagic gastroenteritis following a stay in a pet housing facility. Routine diagnostic investigations failed to identify a specific cause. Virus isolation from fresh necropsy tissues yielded a calicivirus with sequence homology to a vesivirus within the group colloquially known as the vesivirus 2117 strains that were originally identified as contaminants in CHO cell bioreactors. In situ hybridization and reverse transcription-PCR assays of tissues from the four deceased dogs confirmed the presence of canine vesivirus (CaVV) nucleic acids that localized to endothelial cells of arterial and capillary blood vessels. CaVV nucleic acid corresponded to areas of necrosis and hemorrhage primarily in the intestinal tract, but also in the brain of one dog with nonsuppurative meningoencephalitis. This is the first report of an atypical disease association with a putative hypervirulent vesivirus strain in dogs, as all other known strains of CaVV appear to cause nonclinical infections or relatively mild disease. After identification of the CU-296 vesivirus strain from this outbreak, four additional CaVV strains were amplified from unrelated fecal specimens and archived stocks provided by other laboratories. Broader questions include the origins, reservoir(s), and potential for reemergence and spread of these related CaVVs.",,"['Renshaw, Randall W.', 'Griffing, Jennifer', 'Weisman, Jaime', 'Crofton, Lisa M.', 'Laverack, Melissa A.', 'Poston, Robert P.', 'Duhamel, Gerald E.', 'Dubovi, Edward J.']",,,,
,PMC,Validation of the Pockit Dengue Virus Reagent Set for Rapid Detection of Dengue Virus in Human Serum on a Field-Deployable PCR System,http://dx.doi.org/10.1128/JCM.01865-17,PMC5925719,,,"Dengue virus (DENV) infection, a mosquito-borne disease, is a major public health problem in tropical countries. Point-of-care DENV detection with good sensitivity and specificity enables timely early diagnosis of DENV infection, facilitating effective disease management and control, particularly in regions of low resources. The Pockit dengue virus reagent set (GeneReach Biotech), a reverse transcription insulated isothermal PCR (RT-iiPCR), is available to detect all four serotypes of DENV on the field-deployable Pockit system, which is ready for on-site applications. In this study, analytical and clinical performances of the assay were evaluated. The index assay did not react with 14 non-DENV human viruses, indicating good specificity. Compared to the U.S. CDC DENV-1–4 real-time quantitative RT-PCR (qRT-PCR) assay, testing with serial dilutions of virus-spiked human sera demonstrated that the index assay had detection endpoints that were separately comparable with the 4 serotypes. Excellent reproducibility was observed among repeat tests done by six operators at three sites. In clinical performance, 195 clinical sera collected around Kaohsiung city in 2012 and 21 DENV-4-spiked sera were tested with the RT-iiPCR and qRT-PCR assays in parallel. The 121 (11 DENV-1, 78 DENV-2, 11 DENV-3, and 21 DENV-4) qRT-PCR-positive and 95 qRT-PCR-negative samples were all positive and negative by the RT-iiPCR reagent results, respectively, demonstrating high (100%) interrater agreement (95% confidence interval [CI(95%)], ∼98.81% to 100%; κ = 1). With analytical and clinical performance equivalent to those of the reference qRT-PCR assay, the index PCR assay on the field-deployable system can serve as a highly sensitive and specific on-site tool for DENV detection.",,"['Tsai, Jih-Jin', 'Liu, Li-Teh', 'Lin, Ping-Chang', 'Tsai, Ching-Yi', 'Chou, Pin-Hsing', 'Tsai, Yun-Long', 'Chang, Hsiao-Fen Grace', 'Lee, Pei-Yu Alison']",,,,
,PMC,Potential Point-of-Care Testing for Dengue Virus in the Field,http://dx.doi.org/10.1128/JCM.00203-18,PMC5925702,,,"The four serotypes of dengue virus (DENV) cause one of the most important and rapidly emerging mosquito-borne viral diseases in humans. Of the currently available diagnostic tests for dengue, the reverse transcription-PCR (RT-PCR) assay is the most sensitive and specific, and so it is commonly used as the gold standard. However, the requirement of a sophisticated and expensive thermal cycler makes it very difficult to use as a point-of-care diagnostic test in resource-limited regions where dengue is endemic. Tsai et al. (J Clin Microbiol 56:e01865-17, 2018, https://doi.org/10.1128/JCM.01865-17) report the analytical and clinical performances of a reverse transcription-insulated isothermal PCR (RT-iiPCR) assay with a portable nucleic acid analyzer for rapid detection of the four DENV serotypes; its reproducibility and complete agreement on clinical samples with the multiplex RT-PCR assay developed by the Centers for Disease Control and Prevention suggest that the dengue RT-iiPCR is a potential point-of-care test. Compared with other DENV RNA detection methods, the unique isothermal PCR design of RT-iiPCR, together with further improvements, would represent a promising new type of field-deployable diagnostic test for dengue.",,"['Wang, Wei-Kung', 'Gubler, Duane J.']",,,,
,PMC,Hemophagocytic lymphohistiocytosis,http://dx.doi.org/10.1080/08998280.2018.1446877,PMC5997037,,,"Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of widespread inflammation due to massive amounts of cytokines released from activated macrophages. The most common trigger for HLH is infection from a virus, most commonly Epstein-Barr virus. Here we report an adult case of this rare and life-threatening syndrome.",,"['Gowarty, Jasmine', 'Oda, Julie', 'Cable, Christian']",,,,
,PMC,Synthesis and In vitro Leishmanicidal Activities of Six Quercetin Derivatives,http://dx.doi.org/10.4103/abr.abr_76_17,PMC5952540,29862213,CC BY-NC-SA,"BACKGROUND: Today, leishmaniasis is a widespread, infectious parasitic disease caused by Leishmania spp. Natural-derived compounds are likely to provide a valuable source of new pharmaceuticals, and among them, quercetin derivatives may have antileishmanial effects. The antileishmanial activity of 3,5,7,3’,4’-pentahydroxyflavonol (quercetin) derivatives is partly attributed to the position and pKa of phenolic or catechol hydroxyl groups. Therefore, to optimize their leishmanicidal effect, the structural features of quercetin and its derivatives were improved by acylation or alkylation of hydroxyl groups and changing their pKa and consequently their activities. MATERIALS AND METHODS: In this study, during a regioselective method, quercetin derivatives were synthesized. The structures of synthesized compounds were confirmed by mass, IR, (1)H-, and (13)C-NMR spectral data. The antileishmanial activities of compounds 1–6 were compared with glucantime as the standard drug against promastigotes of Leishmania major using standard cell-based leishmanicidal assay. RESULTS: In this study, during a regioselective method, two 7-O-quercetin derivatives (5 and 6), and three quercetin acetate derivatives (2, 3, and 4) were synthesized. In detail, the IC(50) values found against L. major were (1) 2.5 ± 0.92; (2) 2.85 ± 0.99; (3) 15.5 ± 1.95; (4) 13.5 ± 3.5; (5) 2.6 ± 0.57; and (6) 1.3 ± 0.35 μM while IC(50) value of glucantime as the standard drug was 88.5 ± 9.47 μM. CONCLUSIONS: The present study showed an effective antileishmanial activity of quercetin semisynthetic compounds (1–6) against in vitro promastigotes of L. major. Among them, quercetin analogs with more lipophilic and iron-chelating activity showed more antiparasite activity.",2018 Apr 24,"['Mohajeri, Maryam', 'Saghaei, Lotfollah', 'Ghanadian, Mustafa', 'Saberi, Sedighe', 'Pestechian, Nader', 'Ostadhusseini, Ehsan']",Adv Biomed Res,,,
,PMC,Profile of the Alere i Influenza A & B assay: a pioneering molecular point-of-care test,http://dx.doi.org/10.1080/14737159.2018.1466703,PMC6153442,,,"INTRODUCTION: The Alere i Influenza A & B assay incorporates the Nicking Enzyme Amplification Reaction technique on the Alere i instrument to detect and differentiate influenza virus (Flu) A and B nucleic acids in specific specimens. AREAS COVERED: The Alere i Influenza A & B assay was cleared by the US Food and Drug Administration for use with nasal swabs (NS) and nasopharyngeal swabs, either directly or in viral transport medium. Notably, direct use on NS was the first ever CLIA-waived nucleic acid-based test. Previously published evaluations have reported sensitivities and specificities of 55.2–100% and 62.5–100% for Flu A and 45.2–100% and 53.6–100% for Flu B, respectively. EXPERT COMMENTARY: The Alere i Influenza A & B assay provides a rapid and simple platform for detection and differentiation of Flu A and B. Efforts are expected to further improve sensitivity and user-friendliness for effective and widespread use in the true point-of-care setting.",,"['Wang, Hongmei', 'Deng, Jikui', 'Tang, Yi-Wei']",,,,
,PMC,Knowledge and Attitude of Dental Health Professionals about Middle East Respiratory Syndrome in Saudi Arabia,http://dx.doi.org/10.4103/jispcd.JISPCD_9_18,PMC5946522,29780739,CC BY-NC-SA,"AIM AND OBJECTIVE: This study aims to evaluate the knowledge and attitude of practicing dental health professionals (DHPs) (dentist and dental auxiliaries) toward Middle East Respiratory Syndrome coronavirus (MERS-CoV) in Saudi Arabia. MATERIALS AND METHODS: A cross-sectional descriptive study was undertaken among practicing DHPs in Saudi Arabia. A total of 202 DHPs participated in this study. Knowledge and attitude were assessed using self-administered and pretested questionnaire. The questionnaire was administered online through Survey Monkey(®) program by sending link to the registered E-mail. Descriptive statistics were performed on demographic data. Mean knowledge and mean attitude scores of DHPs were calculated. Mann–Whitney U-test and Kruskal–Wallis tests were used to disclose the differences between study variables. Chi-square tests and Spearman's correlation tests were applied to find the associations between the variables. RESULTS: The study participants showed mean knowledge score of 12.26 ± 2.27 (based on 17 knowledge questions) and attitude score of 8.63 ± 1.68 (based on 10 attitude questions). The spearman's test showed the positive correlation between knowledge and attitude of DHPs about MERS (r = 0.093, P = 0.188). Knowledge gaps were reflected in questions related to the duration of infectivity (47.5%), treatment of MERS (39.6%), reservoir of MERS-CoV (38.1%), availability of vaccination against MERS-CoV (25.2%), the likelihood of infection (24.3%), and the type of MERS-CoV (23.3%). DHPs showed a positive attitude toward adherence to universal precautions given by CDC and WHO (0.94 ± 0.25), active participation infection control program (0.94 ± 0.24), and use of gowns, gloves, mask, and goggles while dealing with MERS-CoV patients (0.97 ± 0.17). Male DHPs showed significantly higher knowledge and positive attitude toward MERS-CoV infection compared to females. CONCLUSION: DHPs participated in this study showed good knowledge and positive attitude toward MERS. However, still few lacunae in the knowledge and attitudes toward MERS-CoV were found requiring extensive educational programs.",2018 Apr 24 Mar-Apr,"['Althomairy, Sameer Abdullah', 'Baseer, Mohammad Abdul', 'Assery, Mansour', 'Alsaffan, Abdulrahman Dahham']",J Int Soc Prev Community Dent,,,
,PMC,Neutral Theory and Rapidly Evolving Viral Pathogens,http://dx.doi.org/10.1093/molbev/msy088,PMC6279309,,,"The evolution of viral pathogens is shaped by strong selective forces that are exerted during jumps to new hosts, confrontations with host immune responses and antiviral drugs, and numerous other processes. However, while undeniably strong and frequent, adaptive evolution is largely confined to small parts of information-packed viral genomes, and the majority of observed variation is effectively neutral. The predictions and implications of the neutral theory have proven immensely useful in this context, with applications spanning understanding within-host population structure, tracing the origins and spread of viral pathogens, predicting evolutionary dynamics, and modeling the emergence of drug resistance. We highlight the multiple ways in which the neutral theory has had an impact, which has been accelerated in the age of high-throughput, high-resolution genomics.",,"['Frost, Simon D W', 'Magalis, Brittany Rife', 'Kosakovsky Pond, Sergei L']",,,,
,PMC,Hijacking DNA methyltransferase transition state analogues to produce chemical scaffolds for PRMT inhibitors,http://dx.doi.org/10.1098/rstb.2017.0072,PMC5915716,,,"DNA, RNA and histone methylation is implicated in various human diseases such as cancer or viral infections, playing a major role in cell process regulation, especially in modulation of gene expression. Here we developed a convergent synthetic pathway starting from a protected bromomethylcytosine derivative to synthesize transition state analogues of the DNA methyltransferases. This approach led to seven 5-methylcytosine-adenosine compounds that were, surprisingly, inactive against hDNMT1, hDNMT3Acat, TRDMT1 and other RNA human and viral methyltransferases. Interestingly, compound 4 and its derivative 2 showed an inhibitory activity against PRMT4 in the micromolar range. Crystal structures showed that compound 4 binds to the PRMT4 active site, displacing strongly the S-adenosyl-l-methionine cofactor, occupying its binding site, and interacting with the arginine substrate site through the cytosine moiety that probes the space filled by a substrate peptide methylation intermediate. Furthermore, the binding of the compounds induces important structural switches. These findings open new routes for the conception of new potent PRMT4 inhibitors based on the 5-methylcytosine-adenosine scaffold. This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’.",,"['Halby, Ludovic', 'Marechal, Nils', 'Pechalrieu, Dany', 'Cura, Vincent', 'Franchini, Don-Marc', 'Faux, Céline', 'Alby, Fréderic', 'Troffer-Charlier, Nathalie', 'Kudithipudi, Srikanth', 'Jeltsch, Albert', 'Aouadi, Wahiba', 'Decroly, Etienne', 'Guillemot, Jean-Claude', 'Page, Patrick', 'Ferroud, Clotilde', 'Bonnefond, Luc', ""Guianvarc'h, Dominique"", 'Cavarelli, Jean', 'Arimondo, Paola B.']",,,,
,PMC,Comparing Twitter data to routine data sources in public health surveillance for the 2015 Pan/Parapan American Games: an ecological study,http://dx.doi.org/10.17269/s41997-018-0059-0,PMC6964588,,,"OBJECTIVES: This study examined Twitter for public health surveillance during a mass gathering in Canada with two objectives: to explore the feasibility of acquiring, categorizing and using geolocated Twitter data and to compare Twitter data against other data sources used for Pan Parapan American Games (P/PAG) surveillance. METHODS: Syndrome definitions were created using keyword categorization to extract posts from Twitter. Categories were developed iteratively for four relevant syndromes: respiratory, gastrointestinal, heat-related illness, and influenza-like illness (ILI). All data sources corresponded to the location of Toronto, Canada. Twitter data were acquired from a publicly available stream representing a 1% random sample of tweets from June 26 to September 10, 2015. Cross-correlation analyses of time series data were conducted between Twitter and comparator surveillance data sources: emergency department visits, telephone helpline calls, laboratory testing positivity rate, reportable disease data, and temperature. RESULTS: The frequency of daily tweets that were classified into syndromes was low, with the highest mean number of daily tweets being for ILI and respiratory syndromes (22.0 and 21.6, respectively) and the lowest, for the heat syndrome (4.1). Cross-correlation analyses of Twitter data demonstrated significant correlations for heat syndrome with two data sources: telephone helpline calls (r = 0.4) and temperature data (r = 0.5). CONCLUSION: Using simple syndromes based on keyword classification of geolocated tweets, we found a correlation between tweets and two routine data sources for heat alerts, the only public health event detected during P/PAG. Further research is needed to understand the role for Twitter in surveillance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.17269/s41997-018-0059-0) contains supplementary material, which is available to authorized users.",,"['Khan, Yasmin', 'Leung, Garvin J.', 'Belanger, Paul', 'Gournis, Effie', 'Buckeridge, David L.', 'Liu, Li', 'Li, Ye', 'Johnson, Ian L.']",,,,
,PMC,Correction: MERS-CoV spillover at the camel-human interface,http://dx.doi.org/10.7554/eLife.37324,PMC5908435,29669683,CC BY,,,"['Dudas, Gytis', 'Carvalho, Luiz Max', 'Rambaut, Andrew', 'Bedford, Trevor']",eLife.; 7:e37324,,,
,PMC,Alveolar levels of immuno-inflammatory mediators in diffuse alveolar hemorrhage after allogeneic transplant,http://dx.doi.org/10.1038/s41409-018-0168-7,PMC6474338,,,,,"['Vande Vusse, Lisa K.', 'Wurfel, Mark M.', 'Madtes, David M.', 'Schoch, H. Gary', 'Harju-Baker, Susanna', 'Hill, Joshua A.', 'Jerome, Keith R.', 'Boeckh, Michael', 'Watkins, Timothy R.']",,,,
,PMC,Seeking Out SARI: An Automated Search of Electronic Health Records,http://dx.doi.org/10.1017/S0950268818000699,PMC5997502,,,"The definition of severe acute respiratory infection (SARI)—a respiratory illness with fever and cough, occurring within the past 10 days, and requiring hospital admission—has not been evaluated for critically ill patients. Using integrated electronic health records data, we developed an automated search algorithm to identify SARI cases in a large cohort of critical care patients and evaluate patient outcomes. We conducted a retrospective cohort study of all admissions to a medical intensive care unit from August 2009 through March 2016. Subsets were randomly selected for deriving and validating a search algorithm, which was compared to temporal trends in laboratory-confirmed influenza to ensure that SARI was correlated with influenza. The algorithm was applied to the cohort to identify clinical differences for patients with and without SARI. For identifying SARI, the algorithm (sensitivity, 86.9%; specificity, 95.6%) outperformed billing-based searching (sensitivity, 73.8%; specificity, 78.8%). Automated searching correlated with peaks in laboratory-confirmed influenza. Adjusted for severity of illness, SARI was associated with more hospital, intensive care unit, and ventilator days but not with death or dismissal to home. The search algorithm accurately identified SARI for epidemiologic study and surveillance.",,"['O’Horo, John C.', 'Dziadzko, Mikhail', 'Sakusic, Amra', 'Ali, Rashid', 'Rizwan Sohail, M.', 'Kor, Daryl J.', 'Gajic, Ognjen']",,,,
,PMC,"Burden of Influenza in Less Than 5-Year-Old Children Admitted to Hospital with Pneumonia in Developing and Emerging Countries: A Descriptive, Multicenter Study",http://dx.doi.org/10.4269/ajtmh.17-0494,PMC6086184,,,"This descriptive 4-year study reports the proportion of detection of influenza viruses in less than 5-year-old children hospitalized for pneumonia in eight developing and emerging countries and describes clinical and microbiological characteristics of influenza-related pneumonia cases. Hospitalized children presenting radiologically confirmed pneumonia aged 2–60 months were prospectively enrolled in this observational standardized study. Mean proportion of isolated influenza virus was 9.7% (95% confidence interval: 7.9–11.8%) among 888 pneumonia children analyzed, with moderate heterogeneity between countries—ranging from 6.2% in Cambodia to 18.8% in Haiti. The clinical characteristics of children with influenza-related pneumonia were not substantially different from those of other pneumonia cases. Influenza A H1N1-related pneumonia cases appeared as more severe than pneumonia cases related to other strains of influenza. Streptococcus pneumoniae was detected more often in blood samples from influenza-related cases than in those without detected influenza viruses (19.7% versus 9.5%, P = 0.018). Influenza-related pneumonia is frequent among children less than 5 years old with pneumonia, living in developing and emerging countries. Influenza might be a frequent etiologic agent responsible for pneumonia or a predisposing status factor for pneumococcal-related pneumonia in this population.",,"['Dananché, Cédric', 'Sánchez Picot, Valentina', 'Bénet, Thomas', 'Messaoudi, Mélina', 'Chou, Monidarin', 'Wang, Jianwei', 'Pape, Jean-William', 'Awasthi, Shally', 'Bavdekar, Ashish', 'Rakoto-Andrianarivelo, Mala', 'Sylla, Mariam', 'Nymadawa, Pagbajabyn', 'Russomando, Graciela', 'Komurian-Pradel, Florence', 'Endtz, Hubert', 'Paranhos-Baccalà, Gláucia', 'Vanhems, Philippe', None]",,,,
,PMC,Quality Control Analysis in Real-time (QC-ART): A Tool for Real-time Quality Control Assessment of Mass Spectrometry-based Proteomics Data,http://dx.doi.org/10.1074/mcp.RA118.000648,PMC6126382,,,"Liquid chromatography-mass spectrometry (LC-MS)-based proteomics studies of large sample cohorts can easily require from months to years to complete. Acquiring consistent, high-quality data in such large-scale studies is challenging because of normal variations in instrumentation performance over time, as well as artifacts introduced by the samples themselves, such as those because of collection, storage and processing. Existing quality control methods for proteomics data primarily focus on post-hoc analysis to remove low-quality data that would degrade downstream statistics; they are not designed to evaluate the data in near real-time, which would allow for interventions as soon as deviations in data quality are detected. In addition to flagging analyses that demonstrate outlier behavior, evaluating how the data structure changes over time can aide in understanding typical instrument performance or identify issues such as a degradation in data quality because of the need for instrument cleaning and/or re-calibration. To address this gap for proteomics, we developed Quality Control Analysis in Real-Time (QC-ART), a tool for evaluating data as they are acquired to dynamically flag potential issues with instrument performance or sample quality. QC-ART has similar accuracy as standard post-hoc analysis methods with the additional benefit of real-time analysis. We demonstrate the utility and performance of QC-ART in identifying deviations in data quality because of both instrument and sample issues in near real-time for LC-MS-based plasma proteomics analyses of a sample subset of The Environmental Determinants of Diabetes in the Young cohort. We also present a case where QC-ART facilitated the identification of oxidative modifications, which are often underappreciated in proteomic experiments.",,"['Stanfill, Bryan A.', 'Nakayasu, Ernesto S.', 'Bramer, Lisa M.', 'Thompson, Allison M.', 'Ansong, Charles K.', 'Clauss, Therese R.', 'Gritsenko, Marina A.', 'Monroe, Matthew E.', 'Moore, Ronald J.', 'Orton, Daniel J.', 'Piehowski, Paul D.', 'Schepmoes, Athena A.', 'Smith, Richard D.', 'Webb-Robertson, Bobbie-Jo M.', 'Metz, Thomas O.', None]",,,,
,PMC,Single-Cell Analysis of the Impact of Host Cell Heterogeneity on Infection with Foot-and-Mouth Disease Virus,http://dx.doi.org/10.1128/JVI.00179-18,PMC5899210,,,"Viral infection and replication are affected by host cell heterogeneity, but the mechanisms underlying the effects remain unclear. Using single-cell analysis, we investigated the effects of host cell heterogeneity, including cell size, inclusion, and cell cycle, on foot-and-mouth disease virus (FMDV) infection (acute and persistent infections) and replication. We detected various viral genome replication levels in FMDV-infected cells. Large cells and cells with a high number of inclusions generated more viral RNA copies and viral protein and a higher proportion of infectious cells than other cells. Additionally, we found that the viral titer was 10- to 100-fold higher in cells in G(2)/M than those in other cell cycle phases and identified a strong correlation between cell size, inclusion, and cell cycle heterogeneity, which all affected the infection and replication of FMDV. Furthermore, we demonstrated that host cell heterogeneity influenced the adsorption of FMDV due to differences in the levels of FMDV integrin receptors expression. Collectively, these results further our understanding of the evolution of a virus in a single host cell. IMPORTANCE It is important to understand how host cell heterogeneity affects viral infection and replication. Using single-cell analysis, we found that viral genome replication levels exhibited dramatic variability in foot-and-mouth disease virus (FMDV)-infected cells. We also found a strong correlation between heterogeneity in cell size, inclusion number, and cell cycle status and that all of these characteristics affect the infection and replication of FMDV. Moreover, we found that host cell heterogeneity influenced the viral adsorption as differences in the levels of FMDV integrin receptors' expression. This study provided new ideas for the studies of correlation between FMDV infection mechanisms and host cells.",,"['Xin, Xiu', 'Wang, Hailong', 'Han, Lingling', 'Wang, Mingzhen', 'Fang, Hui', 'Hao, Yao', 'Li, Jiadai', 'Zhang, Hu', 'Zheng, Congyi', 'Shen, Chao']",,,,
,PMC,The Superimposed Deubiquitination Effect of OTULIN and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Nsp11 Promotes Multiplication of PRRSV,http://dx.doi.org/10.1128/JVI.00175-18,PMC5899196,,,"Linear ubiquitination plays an important role in the regulation of the immune response by regulating nuclear factor κB (NF-κB). The linear ubiquitination-specific deubiquitinase ovarian tumor domain deubiquitinase with linear linkage specificity (OTULIN) can control the immune signaling transduction pathway by restricting the Met1-linked ubiquitination process. In our study, the porcine OTLLIN gene was cloned and deubiquitin functions were detected in a porcine reproductive and respiratory syndrome virus (PRRSV)-infected-cell model. PRRSV infection promotes the expression of the OTULIN gene; in turn, overexpression of OTULIN contributes to PRRSV proliferation. There is negative regulation of innate immunity with OTULIN during viral infection. The cooperative effects of swine OTULIN and PRRSV Nsp11 potentiate the ability to reduce levels of cellular protein ubiquitin associated with innate immunity. Importantly, PRRSV Nsp11 recruits OTULIN through a nonenzymatic combination to enhance its ability to remove linear ubiquitination targeting NEMO, resulting in a superimposed effect that inhibits the production of type I interferons (IFNs). Our report presents a new model of virus utilization of the ubiquitin-protease system in vivo from the perspective of the viral proteins that interact with cell deubiquitination enzymes, providing new ideas for prevention and control of PRRSV. IMPORTANCE Deubiquitination effects of swine OTULIN were identified. The interaction between porcine OTULIN and PRRSV Nsp11 is dependent on the OTU domain. PRRSV Nsp11 recruits OTULIN through a nonenzymatic combination to promote removal of linear ubiquitination targeting NEMO, resulting in a superimposed effect that inhibits the production of type I IFNs.",,"['Su, Yanxin', 'Shi, Peidian', 'Zhang, Lilin', 'Lu, Dong', 'Zhao, Chengxue', 'Li, Ruiqiao', 'Zhang, Lei', 'Huang, Jinhai']",,,,
,PMC,Karyopherin Alpha 6 Is Required for Replication of Porcine Reproductive and Respiratory Syndrome Virus and Zika Virus,http://dx.doi.org/10.1128/JVI.00072-18,PMC5899184,,,"Movement of macromolecules between the cytoplasm and the nucleus occurs through the nuclear pore complex (NPC). Karyopherins comprise a family of soluble transport factors facilitating the nucleocytoplasmic translocation of proteins through the NPC. In this study, we found that karyopherin α6 (KPNA6; also known as importin α7) was required for the optimal replication of porcine reproductive and respiratory syndrome virus (PRRSV) and Zika virus (ZIKV), which are positive-sense, single-stranded RNA viruses replicating in the cytoplasm. The KPNA6 protein level in virus-infected cells was much higher than that in mock-infected controls, whereas the KPNA6 transcript remains stable. Viral infection blocked the ubiquitin-proteasomal degradation of KPNA6, which led to an extension of the KPNA6 half-life and the elevation of the KPNA6 level in comparison to mock-infected cells. PRRSV nsp12 protein induced KPNA6 stabilization. KPNA6 silencing was detrimental to the replication of PRRSV, and KPNA6 knockout impaired ZIKV replication. Moreover, KPNA6 knockout blocked the nuclear translocation of PRRSV nsp1β but had a minimal effect on two other PRRSV proteins with nuclear localization. Exogenous restitution of KPNA6 expression in the KPNA6-knockout cells results in restoration of the nuclear translocation of PRRSV nsp1β and the replication of ZIKV. These results indicate that KPNA6 is an important cellular factor for the replication of PRRSV and ZIKV. IMPORTANCE Positive-sense, single-stranded RNA (+ssRNA) viruses replicate in the cytoplasm of infected cells. The roles of transport factors in the nucleocytoplasmic trafficking system for the replication of +ssRNA viruses are not known. In this study, we discovered that PRRSV and ZIKV viruses needed karyopherin α6 (KPNA6), one of the transport factors, to enhance the virus replication. Our data showed that viral infection induced an elevation of the KPNA6 protein level due to an extension of the KPNA6 half-life via viral interference of the ubiquitin-proteasomal degradation of KPNA6. Notably, KPNA6 silencing or knockout dramatically reduced the replication of PRRSV and ZIKV. PRRSV nsp1β depended on KPNA6 to translocate into the nucleus. In addition, exogenous restitution of KPNA6 expression in KPNA6-knockout cells led to the restoration of nsp1β nuclear translocation and ZIKV replication. These results reveal a new aspect in the virus-cell interaction and may facilitate the development of novel antiviral therapeutics.",,"['Yang, Liping', 'Wang, Rong', 'Yang, Shixing', 'Ma, Zexu', 'Lin, Shaoli', 'Nan, Yuchen', 'Li, Qisheng', 'Tang, Qiyi', 'Zhang, Yan-Jin']",,,,
,PMC,A Functional Link between RNA Replication and Virion Assembly in the Potyvirus Plum Pox Virus,http://dx.doi.org/10.1128/JVI.02179-17,PMC5899180,,,"Accurate assembly of viral particles in the potyvirus Plum pox virus (PPV) has been shown to depend on the contribution of the multifunctional viral protein HCPro. In this study, we show that other viral factors, in addition to the capsid protein (CP) and HCPro, are necessary for the formation of stable PPV virions. The CP produced in Nicotiana benthamiana leaves from a subviral RNA termed LONG, which expresses a truncated polyprotein that lacks P1 and HCPro, together with HCPro supplied in trans, was assembled into virus-like particles and remained stable after in vitro incubation. In contrast, deletions in multiple regions of the LONG coding sequence prevented the CP stabilization mediated by HCPro. In particular, we demonstrated that the first 178 amino acids of P3, but not a specific nucleotide sequence coding for them, are required for CP stability and proper assembly of PPV particles. Using a sequential coagroinfiltration assay, we observed that the subviral LONG RNA replicates and locally spreads in N. benthamiana leaves expressing an RNA silencing suppressor. The analysis of the effect of both point and deletion mutations affecting RNA replication in LONG and full-length PPV demonstrated that this process is essential for the assembly of stable viral particles. Interestingly, in spite of this requirement, the CP produced by a nonreplicating viral RNA can be stably assembled into virions as long as it is coexpressed with a replication-proficient RNA. Altogether, these results highlight the importance of coupling encapsidation to other viral processes to secure a successful infection. IMPORTANCE Viruses of the family Potyviridae are among the most dangerous threats for basically every important crop, and such socioeconomical relevance has made them a subject of many research studies. In spite of this, very little is currently known about proteins and processes controlling viral genome encapsidation by the coat protein. In the case of Plum pox virus (genus Potyvirus), for instance, we have previously shown that the multitasking viral factor HCPro plays a role in the production of stable virions. Here, by using this potyvirus as a model, we move further to show that additional factors are also necessary for the efficient production of potyviral particles. More importantly, a comprehensive screening for such factors led us to the identification of a functional link between virus replication and packaging, unraveling a previously unknown connection of these two key events of the potyviral infection cycle.",,"['Gallo, Araiz', 'Valli, Adrian', 'Calvo, María', 'García, Juan Antonio']",,,,
,PMC,Harnessing the Digital Exhaust: Incorporating Wellness into the Pharma Model,http://dx.doi.org/10.1159/000488132,PMC6157915,,,"The increasing availability of devices capable of tracking biomarkers presents major opportunities in contemporary healthcare. Herein we advocate a new role for the pharmaceutical industry to capitalize on these opportunities and, in doing so, incorporate wellness and patient engagement programs into their standard business models. Medical-grade decision-making using diagnostic, prognostic, and monitoring biomarkers will require coordinated approaches between the pharmaceutical and technology industries and the careful design of longitudinal clinical studies to validate their efficacy. These studies will also require data capture, archiving, curating, and sharing on a previously unprecedented scale, and raise additional concerns with regard to data security and ownership. Concurrently, systems-based approaches to the capture and interpretation of a new class of digital biomarkers are emerging, and they hold promise for heightened levels of patient engagement and remote sensing. Collectively, if these new opportunities are approached within the context of the patient-provider ecosystem, major repositioning of the pharmaceutical industry may be possible in the near future.",,"['Wright, Justin M.', 'Jones, Graham Barry']",,,,
,PMC,Anti–Ebola Virus Antibody Levels in Convalescent Plasma and Viral Load After Plasma Infusion in Patients With Ebola Virus Disease,http://dx.doi.org/10.1093/infdis/jiy199,PMC6927845,,,"BACKGROUND: Ebola virus (EBOV) neutralizing antibody in plasma may reduce viral load following administration of plasma to patients with Ebola virus disease (EVD), but measurement of these antibodies is complex. METHODS: Anti-EBOV antibody was measured by 2 neutralization and 2 enzyme-linked immunosorbent assays (ELISAs) in convalescent plasma (ECP) from 100 EVD survivor donors in Liberia. Viral load was assessed repetitively in patients with EVD participating in a clinical trial of enhanced standard of care plus ECP. RESULTS: All 4 anti-EBOV assays were highly concordant for detection of EBOV antibody. Antibodies were not detected in plasma specimens obtained from 15 of 100 donors, including 7 with documented EBOV-positive reverse-transcription polymerase chain reaction during EVD. Viral load was reduced following each dose in the 2 clinical trial participants who received ECP with higher antibody levels but not in the 2 who received ECP with lower antibody levels. CONCLUSIONS: Recovery from EVD can occur with absence of detectable anti-EBOV antibody several months after disease onset. ELISAs may be useful to select ECP donors or identify ECP units that contain neutralizing antibody. ECP with higher anti-EBOV antibody levels may have greater effect on EBOV load—an observation that requires further investigation. CLINICAL TRIALS REGISTRATION: NCT02333578.",,"['Brown, Jerry F', 'Dye, John M', 'Tozay, Sam', 'Jeh-Mulbah, Gertrude', 'Wohl, David A', 'Fischer, William A', 'Cunningham, Coleen K', 'Rowe, Kathleen', 'Zacharias, Peter', 'van Hasselt, James', 'Norwood, David A', 'Thielman, Nathan M', 'Zak, Samantha E', 'Hoover, David L']",,,,
,PMC,Jordan Field Epidemiology Training Program: Critical Role in National and Regional Capacity Building,http://dx.doi.org/10.2196/mededu.9516,PMC5917079,29643050,CC BY,"Field Epidemiology Training Programs (FETPs) are 2-year training programs in applied epidemiology, established with the purpose of increasing a country’s capacity within the public health workforce to detect and respond to health threats and develop internal expertise in field epidemiology. The Jordan Ministry of Health, in partnership with the US Centers for Disease Control and Prevention, started the Jordan FETP (J-FETP) in 1998. Since then, it has achieved a high standard of success and has been established as a model for FETPs in the Eastern Mediterranean Region. Here we describe the J-FETP, its role in building the epidemiologic capacity of Jordan’s public health workforce, and its activities and achievements, which have grown the program to be self-sustaining within the Jordan Ministry of Health. Since its inception, the program’s residents and graduates have assisted the country to improve its surveillance systems, including revising the mortality surveillance policy, implementing the use of electronic data reporting, investigating outbreaks at national and regional levels, contributing to noncommunicable disease research and surveillance, and responding to regional emergencies and disasters. J-FETP’s structure and systems of support from the Jordan Ministry of Health and local, regional, and international partners have contributed to the success and sustainability of the J-FETP. The J-FETP has contributed significantly to improvements in surveillance systems, control of infectious diseases, outbreak investigations, and availability of reliable morbidity and mortality data in Jordan. Moreover, the program has supported public health and epidemiology in the Eastern Mediterranean Region. Best practices of the J-FETP can be applied to FETPs throughout the world.",2018 Apr 11,"['Al Nsour, Mohannad', 'Iblan, Ibrahim', 'Tarawneh, Mohammed Rasoul']",JMIR Med Educ,,,
,PMC,The evolution of nucleoside analogue antivirals: A review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold,http://dx.doi.org/10.1016/j.antiviral.2018.04.004,PMC6396324,,,"This is the first of two invited articles reviewing the development of nucleoside-analogue antiviral drugs, written for a target audience of virologists and other non-chemists, as well as chemists who may not be familiar with the field. Rather than providing a simple chronological account, we have examined and attempted to explain the thought processes, advances in synthetic chemistry and lessons learned from antiviral testing that led to a few molecules being moved forward to eventual approval for human therapies, while others were discarded. The present paper focuses on early, relatively simplistic changes made to the nucleoside scaffold, beginning with modifications of the nucleoside sugars of Ara-C and other arabinose-derived nucleoside analogues in the 1960’s. A future paper will review more recent developments, focusing especially on more complex modifications, particularly those involving multiple changes to the nucleoside scaffold. We hope that these articles will help virologists and others outside the field of medicinal chemistry to understand why certain drugs were successfully developed, while the majority of candidate compounds encountered barriers due to low-yielding synthetic routes, toxicity or other problems that led to their abandonment.",,"['Seley-Radtke, Katherine L.', 'Yates, Mary K.']",,,,
,PMC,Development of a prediction tool for patients presenting with acute cough in primary care: a prognostic study spanning six European countries,http://dx.doi.org/10.3399/bjgp18X695789,PMC5916081,,,"BACKGROUND: Accurate prediction of the course of an acute cough episode could curb antibiotic overprescribing, but is still a major challenge in primary care. AIM: The authors set out to develop a new prediction rule for poor outcome (re-consultation with new or worsened symptoms, or hospital admission) in adults presenting to primary care with acute cough. DESIGN AND SETTING: Data were collected from 2604 adults presenting to primary care with acute cough or symptoms suggestive of lower respiratory tract infection (LRTI) within the Genomics to combat Resistance against Antibiotics in Community-acquired LRTI in Europe (GRACE; www.grace-lrti.org) Network of Excellence. METHOD: Important signs and symptoms for the new prediction rule were found by combining random forest and logistic regression modelling. Performance to predict poor outcome in acute cough patients was compared with that of existing prediction rules, using the models’ area under the receiver operator characteristic curve (AUC), and any improvement obtained by including additional test results (C-reactive protein [CRP], blood urea nitrogen [BUN], chest radiography, or aetiology) was evaluated using the same methodology. RESULTS: The new prediction rule, included the baseline Risk of poor outcome, Interference with daily activities, number of years stopped Smoking (> or <45 years), severity of Sputum, presence of Crackles, and diastolic blood pressure (> or <85 mmHg) (RISSC85). Though performance of RISSC85 was moderate (sensitivity 62%, specificity 59%, positive predictive value 27%, negative predictive value 86%, AUC 0.63, 95% confidence interval [CI] = 0.61 to 0.67), it outperformed all existing prediction rules used today (highest AUC 0.53, 95% CI = 0.51 to 0.56), and could not be significantly improved by including additional test results (highest AUC 0.64, 95% CI = 0.62 to 0.68). CONCLUSION: The new prediction rule outperforms all existing alternatives in predicting poor outcome in adult patients presenting to primary care with acute cough and could not be improved by including additional test results.",,"['Bruyndonckx, Robin', 'Hens, Niel', 'Verheij, Theo JM', 'Aerts, Marc', 'Ieven, Margareta', 'Butler, Christopher C', 'Little, Paul', 'Goossens, Herman', 'Coenen, Samuel', None]",,,,
,PMC,A Universal Approach to Optimize the Folding and Stability of Prefusion-Closed HIV-1 Envelope Trimers,http://dx.doi.org/10.1016/j.celrep.2018.03.061,PMC6010203,,,"The heavily glycosylated native-like envelope (Env) trimer of HIV-1 is expected to have low immunogenicity, whereas misfolded forms are often highly immunogenic. High-quality correctly folded Envs may therefore be critical for developing a vaccine that induces broadly neutralizing antibodies. Moreover, the high variability of Env may require immunizations with multiple Envs. Here, we report a universal strategy that provides for correctly folded Env trimers of high quality and yield through a repair-and-stabilize approach. In the repair stage, we utilized a consensus strategy that substituted rare strain-specific residues with more prevalent ones. The stabilization stage involved structure-based design and experimental assessment confirmed by crystallographic feedback. Regions important for the refolding of Env were targeted for stabilization. Notably, the α9-helix and an intersubunit β sheet proved to be critical for trimer stability. Our approach provides a means to produce prefusion-closed Env trimers from diverse HIV-1 strains, a substantial advance for vaccine development.",,"['Rutten, Lucy', 'Lai, Yen-Ting', 'Blokland, Sven', 'Truan, Daphne', 'Bisschop, Ilona J.M.', 'Strokappe, Nika M.', 'Koornneef, Annemart', 'van Manen, Danielle', 'Chuang, Gwo-Yu', 'Farney, S. Katie', 'Schuitemaker, Hanneke', 'Kwong, Peter D.', 'Langedijk, Johannes P.M.']",,,,
,PMC,"Infectious, inflammatory and ‘autoimmune’ male factor infertility: how do rodent models inform clinical practice?",http://dx.doi.org/10.1093/humupd/dmy009,PMC6016649,,,"BACKGROUND: Infection and inflammation of the reproductive tract are significant causes of male factor infertility. Ascending infections caused by sexually transmitted bacteria or urinary tract pathogens represent the most frequent aetiology of epididymo-orchitis, but viral, haematogenous dissemination is also a contributory factor. Limitations in adequate diagnosis and therapy reflect an obvious need for further understanding of human epididymal and testicular immunopathologies and their contribution to infertility. A major obstacle for advancing our knowledge is the limited access to suitable tissue samples. Similarly, the key events in the inflammatory or autoimmune pathologies affecting human male fertility are poorly amenable to close examination. Moreover, the disease processes generally have occurred long before the patient attends the clinic for fertility assessment. In this regard, data obtained from experimental animal models and respective comparative analyses have shown promise to overcome these restrictions in humans. OBJECTIVE AND RATIONALE: This narrative review will focus on male fertility disturbances caused by infection and inflammation, and the usefulness of the most frequently applied animal models to study these conditions. SEARCH METHODS: An extensive search in Medline database was performed without restrictions until January 2018 using the following search terms: ‘infection’ and/or ‘inflammation’ and ‘testis’ and/or ‘epididymis’, ‘infection’ and/or ‘inflammation’ and ‘male genital tract’, ‘male infertility’, ‘orchitis’, ‘epididymitis’, ‘experimental autoimmune’ and ‘orchitis’ or ‘epididymitis’ or ‘epididymo-orchitis’, antisperm antibodies’, ‘vasectomy’. In addition to that, reference lists of primary and review articles were reviewed for additional publications independently by each author. Selected articles were verified by each two separate authors and discrepancies discussed within the team. OUTCOMES: There is clear evidence that models mimicking testicular and/or epididymal inflammation and infection have been instructive in a better understanding of the mechanisms of disease initiation and progression. In this regard, rodent models of acute bacterial epididymitis best reflect the clinical situation in terms of mimicking the infection pathway, pathogens selected and the damage, such as fibrotic transformation, observed. Similarly, animal models of acute testicular and epididymal inflammation using lipopolysaccharides show impairment of reproduction, endocrine function and histological tissue architecture, also seen in men. Autoimmune responses can be studied in models of experimental autoimmune orchitis (EAO) and vasectomy. In particular, the early stages of EAO development showing inflammatory responses in the form of peritubular lymphocytic infiltrates, thickening of the lamina propria of affected tubules, production of autoantibodies against testicular antigens or secretion of pro-inflammatory mediators, replicate observations in testicular sperm extraction samples of patients with ‘mixed atrophy’ of spermatogenesis. Vasectomy, in the form of sperm antibodies and chronic inflammation, can also be studied in animal models, providing valuable insights into the human response. WIDER IMPLICATIONS: This is the first comprehensive review of rodent models of both infectious and autoimmune disease of testis/epididymis, and their clinical implications, i.e. their importance in understanding male infertility related to infectious and non-infectious/autoimmune disease of the reproductive organs.",,"['Fijak, Monika', 'Pilatz, Adrian', 'Hedger, Mark P', 'Nicolas, Nour', 'Bhushan, Sudhanshu', 'Michel, Vera', 'Tung, Kenneth S K', 'Schuppe, Hans-Christian', 'Meinhardt, Andreas']",,,,
,PMC,The use of pyrosequencing for detection of hemagglutinin mutations associated with increased pathogenicity of H5N1 avian influenza viruses in mammals,http://dx.doi.org/10.1177/1040638718769951,PMC6505906,,,"Hemagglutinin (HA) cleavage is critical for virulence of influenza viruses. The amino acid residue at the P6 position of the HA cleavage site (HACS) has been shown to be most variable and to have a direct correlation with the cleavage efficiency and pathogenicity of H5N1 avian influenza viruses (AIVs) in mammals. Among these amino acid variants, serine has been associated with the highest virulence in mammals, and its detection may serve as an indicator for H5N1 AIVs with high pathogenicity and potential public risk. We developed a rapid detection method based on reverse-transcription (RT)-PCR and pyrosequencing to detect a mutation at the HACS that is associated with increased pathogenicity of H5N1 AIVs in mammals. Herein, we provide a specific, sensitive, and reliable method for rapid detection of one of the virulence determinants associated with increased pathogenicity of H5N1 AIVs in mammals.",,"['Wang, Chenxi', 'Zhang, Yongning', 'Bing, Guoxia', 'Zhang, Xuxiao', 'Wang, Caixia', 'Wang, Mingyang', 'Sun, Yipeng', 'Wu, Shaoqiang', 'Lin, Xiangmei', 'Pu, Juan', 'Liu, Jinhua', 'Sun, Honglei']",,,,
,PMC,Impact of Public Health Responses During a Measles Outbreak in an Amish Community in Ohio: Modeling the Dynamics of Transmission,http://dx.doi.org/10.1093/aje/kwy082,PMC6118071,,,"We quantified measles transmissibility during a measles outbreak in Ohio in 2014 to evaluate the impact of public health responses. Case incidence and the serial interval (time between symptom onset in primary cases and secondary cases) were used to assess trends in the effective reproduction number R (the average number of secondary cases generated per case). A mathematical model was parameterized using early R values to determine the size and duration of the outbreak that would have occurred if containment measures had not been initiated, as well as the impact of vaccination. As containment started, we found a 4-fold decline in R (from approximately 4 to 1) over the course of 2 weeks and maintenance of R < 1 as control measures continued. Under a conservative scenario, the model estimated 8,472 cases (90% confidence interval (CI): 8,447, 8,489) over 195 days (90% CI: 179, 223) without control efforts and 715 cases (90% CI: 103, 1,338) over 128 days (90% CI: 117, 139) when vaccination was included; 7,757 fewer cases (90% CI: 7,130, 8,365) and 67 fewer outbreak days (90% CI: 48, 98) were attributed to vaccination. Vaccination may not account entirely for transmission reductions, suggesting that changes in community behavior (social distancing) and other control efforts (isolation, quarantining) are important. Our findings highlight the benefits of measles outbreak response and of understanding behavior change dynamics.",,"['Gastañaduy, Paul A', 'Funk, Sebastian', 'Paul, Prabasaj', 'Tatham, Lilith', 'Fisher, Nicholas', 'Budd, Jeremy', 'Fowler, Brian', 'de Fijter, Sietske', 'DiOrio, Mary', 'Wallace, Gregory S', 'Grenfell, Bryan']",,,,
,PMC,Structure versus stochasticity – The role of molecular crowding and intrinsic disorder in membrane fission,http://dx.doi.org/10.1016/j.jmb.2018.03.024,PMC6045432,,,"Cellular membranes must undergo remodeling to facilitate critical functions including membrane trafficking, organelle biogenesis, and cell division. An essential step in membrane remodeling is membrane fission, in which an initially continuous membrane surface is divided into multiple, separate compartments. The established view has been that membrane fission requires proteins with conserved structural features such as helical scaffolds, hydrophobic insertions, and polymerized assemblies. In this review we discuss these structure-based fission mechanisms and highlight recent findings from several groups that support an alternative, structure-independent mechanism of membrane fission. This mechanism relies on lateral collisions among crowded, membrane-bound proteins to generate sufficient steric pressure to drive membrane vesiculation. As a stochastic process, this mechanism contrasts with the paradigm that deterministic protein structures are required to drive fission, raising the prospect that many more proteins may participate in fission than previously thought. Paradoxically, our recent work suggests that intrinsically disordered domains may be among the most potent drivers of membrane fission, owing to their large hydrodynamic radii and substantial chain entropy. This stochastic view of fission also suggests new roles for the structure-based fission proteins. Specifically, we hypothesize that in addition to driving fission directly, the canonical fission machines may facilitate the enrichment and organization of bulky disordered protein domains in order to promote membrane fission by locally amplifying protein crowding.",,"['Snead, Wilton T.', 'Stachowiak, Jeanne C.']",,,,
,PMC,"Contents, Followers, and Retweets of the Centers for Disease Control and Prevention’s Office of Advanced Molecular Detection (@CDC_AMD) Twitter Profile: Cross-Sectional Study",http://dx.doi.org/10.2196/publichealth.8737,PMC5902693,29610112,CC BY,"BACKGROUND: The Office of Advanced Molecular Detection (OAMD), Centers for Disease Control and Prevention (CDC), manages a Twitter profile (@CDC_AMD). To our knowledge, no prior study has analyzed a CDC Twitter handle’s entire contents and all followers. OBJECTIVE: This study aimed to describe the contents and followers of the Twitter profile @CDC_AMD and to assess if attaching photos or videos to tweets posted by @CDC_AMD would increase retweet frequency. METHODS: Data of @CDC_AMD were retrieved on November 21, 2016. All followers (N=809) were manually categorized. All tweets (N=768) were manually coded for contents and whether photos or videos were attached. Retweet count for each tweet was recorded. Negative binomial regression models were applied to both the original and the retweet corpora. RESULTS: Among the 809 followers, 26.0% (210/809) were individual health professionals, 11.6% (94/809) nongovernmental organizations, 3.3% (27/809) government agencies’ accounts, 3.3% (27/809) accounts of media organizations and journalists, and 0.9% (7/809) academic journals, with 54.9% (444/809) categorized as miscellaneous. A total of 46.9% (360/768) of @CDC_AMD’s tweets referred to the Office’s website and their current research; 17.6% (135/768) referred to their scientists’ publications. Moreover, 80% (69/86) of tweets retweeted by @CDC_AMD fell into the miscellaneous category. In addition, 43.4% (333/768) of the tweets contained photos or videos, whereas the remaining 56.6% (435/768) did not. Attaching photos or videos to original @CDC_AMD tweets increases the number of retweets by 37% (probability ratio=1.37, 95% CI 1.13-1.67, P=.002). Content topics did not explain or modify this association. CONCLUSIONS: This study confirms CDC health communicators’ experience that original tweets created by @CDC_AMD Twitter profile sharing images or videos (or their links) received more retweets. The current policy of attaching images to tweets should be encouraged.",2018 Apr 2,"['Fung, Isaac Chun-Hai', 'Jackson, Ashley M', 'Mullican, Lindsay A', 'Blankenship, Elizabeth B', 'Goff, Mary Elizabeth', 'Guinn, Amy J', 'Saroha, Nitin', 'Tse, Zion Tsz Ho']",JMIR Public Health Surveill,,,
,PMC,First report of atypical porcine pestivirus in piglets with congenital tremor in Canada,,PMC5855290,,,,,"['Dessureault, Fanny G.', 'Choinière, Martin', 'Provost, Chantale', 'Gagnon, Carl A.']",,,,
,PMC,Brain Iron Distribution after Multiple Doses of Ultra-small Superparamagnetic Iron Oxide Particles in Rats,,PMC5897970,,,"The purpose of this study is to determine the effects of high cumulative doses of ultra-small paramagnetic iron oxide (USPIO) used in neuroimaging studies. We intravenously administered 8 mg/kg of 2 USPIO compounds daily for 4 wk to male Sprague–Dawley rats (Crl:SD). Multiecho gradient-echo MRI, serum iron levels, and histology were performed at the end of dosing and after a 7-d washout period. R2* maps and quantitative susceptibility maps (QSM) were generated from multiecho gradient-echo data. R2* maps and QSM showed iron accumulation in brain ventricles on MR images acquired at the 4- and 5-wk time points. Estimates from QSM data showed ventricular iron concentration was equal to or higher than serum iron concentration. Histologic analysis revealed choroid plexus hemosiderosis and midbrain vacuolation, without iron deposition in brain parenchyma. Serum iron levels increased with administration of both compounds, and a 7-d washout period effectively reduced serum iron levels of one but not both of the compounds. High cumulative doses from multiple, frequent administrations of USPIO can lead to iron deposition in brain ventricles, resulting in persistent signal loss on T2*-weighted images. Techniques such as QSM are helpful in quantifying iron biodistribution in this situation.",,"['Gorman, Andrew W', 'Deh, Kofi M', 'Schwiedrzik, Caspar M', 'White, Julie R', 'Groman, Ernest Victor', 'Fisher, Clark A', 'Gillen, Kelly M', 'Spincemaille, Pascal', 'Rasmussen, Skye', 'Prince, Martin R', 'Voss, Henning U', 'Freiwald, Winrich A', 'Wang, Yi']",,,,
,PMC,"PTX3, a Humoral Pattern Recognition Molecule, in Innate Immunity, Tissue Repair and Cancer",http://dx.doi.org/10.1152/physrev.00016.2017,PMC5985957,,,"Innate immunity includes a cellular and a humoral arm. PTX3 is a fluid phase pattern recognition molecule (PRM) conserved in evolution which acts as a key component of humoral innate immunity in infections of fungal, bacterial and viral origin. PTX3 binds conserved microbial structures and self-components under conditions of inflammation and activates effector functions (complement, phagocytosis). Moreover, it has a complex regulatory role in inflammation, such as ischemia/reperfusion injury and cancer-related inflammation, as well as in extracellular matrix organization and remodeling, with profound implications in physiology and pathology. Finally, PTX3 acts as an extrinsic oncosuppressor gene by taming tumor promoting inflammation in murine and selected human tumors. Thus, evidence suggests that PTX3 is a key homeostatic component at the crossroad of innate immunity, inflammation, tissue repair and cancer. Dissecting the complexity of PTX3 pathophysiology and human genetics paves the way to diagnostic and therapeutic exploitation.",,"['Garlanda, Cecilia', 'Bottazzi, Barbara', 'Magrini, Elena', 'Inforzato, Antonio', 'Mantovani, Alberto']",,,,
,PMC,Structure and Immune Recognition of the HIV Glycan Shield,http://dx.doi.org/10.1146/annurev-biophys-060414-034156,PMC6163090,,,"Vaccine design efforts against the human immunodeficiency virus (HIV) have been greatly stimulated by the observation that many infected patients eventually develop highly potent, broadly neutralizing antibodies (bnAbs). Importantly, these bnAbs have evolved to recognize not only the two protein components of the viral envelope protein (Env), but also the numerous glycans that form a protective barrier on the Env protein. Because Env is vastly over-glycosylated compared to host glycoproteins, the glycans have become targets for the antibody response. Therefore, considerable efforts have been made in developing and validating biophysical methods to elucidate the complex structure of the Env spike glycoprotein with its combination of glycan and protein epitopes. We illustrate here how the application of robust biophysical methods have transformed our understanding of the structure and function of the HIV Env spike and stimulated innovation in vaccine design strategies that takes into account the essential glycan components.",,"['Crispin, Max', 'Ward, Andrew B.', 'Wilson, Ian A.']",,,,
,PMC,Does Eating Chicken Feet With Pickled Peppers Cause Avian Influenza? Observational Case Study on Chinese Social Media During the Avian Influenza A (H7N9) Outbreak,http://dx.doi.org/10.2196/publichealth.8198,PMC5897620,29599109,CC BY,"BACKGROUND: A hot topic on the relationship between a popular avian-origin food and avian influenza occurred on social media during the outbreak of the emerging avian influenza A (H7N9). The misinformation generated from this topic had caused great confusion and public concern. OBJECTIVE: Our goals were to analyze the trend and contents of the relevant posts during the outbreak. We also aimed to understand the characteristics of the misinformation and to provide suggestions to reduce public misconception on social media during the emerging disease outbreak. METHODS: The original microblog posts were collected from China’s Sina Weibo and Tencent Weibo using a combination of keywords between April 1, 2013 and June 2, 2013. We analyzed the weekly and daily trend of the relevant posts. Content analyses were applied to categorize the posts into 4 types with unified sorting criteria. The posts’ characteristics and geographic locations were also analyzed in each category. We conducted further analysis on the top 5 most popular misleading posts. RESULTS: A total of 1680 original microblog posts on the topic were retrieved and 341 (20.30%) of these posts were categorized as misleading messages. The number of relevant posts had not increased much during the first 2 weeks but rose to a high level in the next 2 weeks after the sudden increase in number of reported cases at the beginning of week 3. The posts under “misleading messages” occurred and increased from the beginning of week 3, but their daily posting number decreased when the daily number of posts under “refuting messages” outnumbered them. The microbloggers of the misleading posts had the lowest mean rank of followers and previous posts, but their posts had a highest mean rank of posts. The proportion of “misleading messages” in places with no reported cases was significantly higher than that in the epidemic areas (23.6% vs 13.8%). The popular misleading posts appeared to be short and consisted of personal narratives, which were easily disseminated on social media. CONCLUSIONS: Our findings suggested the importance of responding to common questions and misconceptions on social media platforms from the beginning of disease outbreaks. Authorities need to release clear and reliable information related to the popular topics early on. The microbloggers posting correct information should be empowered and their posts could be promoted to clarify false information. Equal importance should be attached to clarify misinformation in both the outbreak and nonoutbreak areas.",2018 Mar 29,"['Chen, Bin', 'Shao, Jian', 'Liu, Kui', 'Cai, Gaofeng', 'Jiang, Zhenggang', 'Huang, Yuru', 'Gu, Hua', 'Jiang, Jianmin']",JMIR Public Health Surveill,,,
,PMC,Purification of Highly Active Alphavirus Replication Complexes Demonstrates Altered Fractionation of Multiple Cellular Membranes,http://dx.doi.org/10.1128/JVI.01852-17,PMC5874421,,,"Positive-strand RNA viruses replicate their genomes in membrane-associated structures; alphaviruses and many other groups induce membrane invaginations called spherules. Here, we established a protocol to purify these membranous replication complexes (RCs) from cells infected with Semliki Forest virus (SFV). We isolated SFV spherules located on the plasma membrane and further purified them using two consecutive density gradients. This revealed that SFV infection strongly modifies cellular membranes. We removed soluble proteins, the Golgi membranes, and most of the mitochondria, but plasma membrane, endoplasmic reticulum (ER), and late endosome markers were retained in the membrane fraction that contained viral RNA synthesizing activity, replicase proteins, and minus- and plus-strand RNA. Electron microscopy revealed that the purified membranes displayed spherule-like structures with a narrow neck. This membrane enrichment was specific to viral replication, as such a distribution of membrane markers was only observed after infection. Besides the plasma membrane, SFV infection remodeled the ER, and the cofractionation of the RC-carrying plasma membrane and ER suggests that SFV recruits ER proteins or membrane to the site of replication. The purified RCs were highly active in synthesizing both genomic and subgenomic RNA. Detergent solubilization destroyed the replication activity, demonstrating that the membrane association of the complex is essential. Most of the newly made RNA was in double-stranded replicative molecules, but the purified complexes also produced single-stranded RNA as well as released newly made RNA. This indicates that the purification established here maintained the functionality of RCs and thus enables further structural and functional studies of active RCs. IMPORTANCE Similar to all positive-strand RNA viruses, the arthropod-borne alphaviruses induce membranous genome factories, but little is known about the arrangement of viral replicase proteins and the presence of host proteins in these replication complexes. To improve our knowledge of alphavirus RNA-synthesizing complexes, we isolated and purified them from infected mammalian cells. Detection of viral RNA and in vitro replication assays revealed that these complexes are abundant and highly active when located on the plasma membrane. After multiple purification steps, they remain functional in synthesizing and releasing viral RNA. Besides the plasma membrane, markers for the endoplasmic reticulum and late endosomes were enriched with the replication complexes, demonstrating that alphavirus infection modified cellular membranes beyond inducing replication spherules on the plasma membrane. We have developed here a gentle purification method to obtain large quantities of highly active replication complexes, and similar methods can be applied to other positive-strand RNA viruses.",,"['Pietilä, Maija K.', 'van Hemert, Martijn J.', 'Ahola, Tero']",,,,
,PMC,Porcine Epidemic Diarrhea Virus-Induced Epidermal Growth Factor Receptor Activation Impairs the Antiviral Activity of Type I Interferon,http://dx.doi.org/10.1128/JVI.02095-17,PMC5874413,,,"Porcine epidemic diarrhea virus (PEDV) causes acute and devastating enteric disease in suckling piglets and results in huge economic losses in the pig industry worldwide. To establish productive infection, viruses must first circumvent the host innate immune response. In this study, we found that PEDV infection stimulated epidermal growth factor receptor (EGFR) activation, which has been linked to not only anticancer therapeutics, but also antiviral signaling. Therefore, we determined whether EGFR activation affected PEDV infection by using an activator or overexpression assay. The data showed that EGFR activation enhanced virus replication in both cases. We also found that specific inhibition of EGFR by either inhibitors or small interfering RNA (siRNA) led to a decrease in virus yields. Further analysis revealed that inhibition of EGFR produced augmentation of type I interferon genes. We next observed that the EGFR downstream cascade STAT3 was also activated upon PEDV infection. Similar to the case of EGFR, specific inhibition of STAT3 by either inhibitor or siRNA increased the antiviral activity of interferon and resulted in decreased PEDV RNA levels, and vice versa. The data on STAT3 depletion in combination with EGFR activation suggest that the attenuation of antiviral activity by EGFR activation requires activation of the STAT3 signaling pathway. Taken together, these data demonstrate that PEDV-induced EGFR activation serves as a negative regulator of the type I interferon response and provides a novel therapeutic target for virus infection. IMPORTANCE EGFR is a transmembrane tyrosine receptor that mediates various cellular events, as well as several types of human cancers. In this study, we investigated for the first time the role of EGFR in PEDV infection. We observed that PEDV infection induced EGFR activation. The role of EGFR activation is to impair the antiviral activity of type I interferon, which requires the involvement of the EGFR downstream signaling cascade STAT3. Our findings reveal a new mechanism evolved by PEDV to circumvent the host antiviral response, which might serve as a therapeutic target against virus infection.",,"['Yang, Lijun', 'Xu, Jiayu', 'Guo, Longjun', 'Guo, Taijie', 'Zhang, Lu', 'Feng, Li', 'Chen, Hongyan', 'Wang, Yue']",,,,
,PMC,"Model of OSBP-Mediated Cholesterol Supply to Aichi Virus RNA Replication Sites Involving Protein-Protein Interactions among Viral Proteins, ACBD3, OSBP, VAP-A/B, and SAC1",http://dx.doi.org/10.1128/JVI.01952-17,PMC5874406,,,"Positive-strand RNA viruses, including picornaviruses, utilize cellular machinery for genome replication. Previously, we reported that each of the 2B, 2BC, 2C, 3A, and 3AB proteins of Aichi virus (AiV), a picornavirus, forms a complex with the Golgi apparatus protein ACBD3 and phosphatidylinositol 4-kinase IIIβ (PI4KB) at viral RNA replication sites (replication organelles [ROs]), enhancing PI4KB-dependent phosphatidylinositol 4-phosphate (PI4P) production. Here, we demonstrate AiV hijacking of the cellular cholesterol transport system involving oxysterol-binding protein (OSBP), a PI4P-binding cholesterol transfer protein. AiV RNA replication was inhibited by silencing cellular proteins known to be components of this pathway, OSBP, the ER membrane proteins VAPA and VAPB (VAP-A/B), the PI4P-phosphatase SAC1, and PI-transfer protein β. OSBP, VAP-A/B, and SAC1 were present at RNA replication sites. We also found various previously unknown interactions among the AiV proteins (2B, 2BC, 2C, 3A, and 3AB), ACBD3, OSBP, VAP-A/B, and SAC1, and the interactions were suggested to be involved in recruiting the component proteins to AiV ROs. Importantly, the OSBP-2B interaction enabled PI4P-independent recruitment of OSBP to AiV ROs, indicating preferential recruitment of OSBP among PI4P-binding proteins. Protein-protein interaction-based OSBP recruitment has not been reported for other picornaviruses. Cholesterol was accumulated at AiV ROs, and inhibition of OSBP-mediated cholesterol transfer impaired cholesterol accumulation and AiV RNA replication. Electron microscopy showed that AiV-induced vesicle-like structures were close to ER membranes. Altogether, we conclude that AiV directly recruits the cholesterol transport machinery through protein-protein interactions, resulting in formation of membrane contact sites between the ER and AiV ROs and cholesterol supply to the ROs. IMPORTANCE Positive-strand RNA viruses utilize host pathways to modulate the lipid composition of viral RNA replication sites for replication. Previously, we demonstrated that Aichi virus (AiV), a picornavirus, forms a complex comprising certain proteins of AiV, the Golgi apparatus protein ACBD3, and the lipid kinase PI4KB to synthesize PI4P lipid at the sites for AiV RNA replication. Here, we confirmed cholesterol accumulation at the AiV RNA replication sites, which are established by hijacking the host cholesterol transfer machinery mediated by a PI4P-binding cholesterol transfer protein, OSBP. We showed that the component proteins of the machinery, OSBP, VAP, SAC1, and PITPNB, are all essential host factors for AiV replication. Importantly, the machinery is directly recruited to the RNA replication sites through previously unknown interactions of VAP/OSBP/SAC1 with the AiV proteins and with ACBD3. Consequently, we propose a specific strategy employed by AiV to efficiently accumulate cholesterol at the RNA replication sites via protein-protein interactions.",,"['Ishikawa-Sasaki, Kumiko', 'Nagashima, Shigeo', 'Taniguchi, Koki', 'Sasaki, Jun']",,,,
,PMC,Cryo-EM Elucidation of the Structure of Bacteriophage P22 Virions after Genome Release,http://dx.doi.org/10.1016/j.bpj.2018.01.026,PMC5883611,,,"Genome ejection proteins are required to facilitate transport of bacteriophage P22 double-stranded DNA safely through membranes of Salmonella. The structures and locations of all proteins in the context of the mature virion are known, with the exception of three ejection proteins. Furthermore, the changes that occur to the proteins residing in the mature virion upon DNA release are not fully understood. We used cryogenic electron microscopy to obtain what is, to our knowledge, the first asymmetric reconstruction of mature bacteriophage P22 after double-stranded DNA has been extruded from the capsid—a state representative of one step during viral infection. Results of icosahedral and asymmetric reconstructions at estimated resolutions of 7.8 and 12.5 Å resolutions, respectively, are presented. The reconstruction shows tube-like protein density extending from the center of the tail assembly. The portal protein does not revert to the more contracted, procapsid state, but instead maintains an extended and splayed barrel structure. These structural details contribute to our understanding of the molecular mechanism of P22 phage infection and also set the foundation for future exploitation serving engineering purposes.",,"['McNulty, Reginald', 'Cardone, Giovanni', 'Gilcrease, Eddie B.', 'Baker, Timothy S.', 'Casjens, Sherwood R.', 'Johnson, John E.']",,,,
,PMC,What We Learned from Ebola: Preparing Dialysis Units for the Next Outbreak,http://dx.doi.org/10.2215/CJN.11061017,PMC5968910,,,,,"['Boyce, John M.', 'Hymes, Jeffrey L.']",,,,
,PMC,A Highly Pathogenic Strain of Porcine Deltacoronavirus Caused Watery Diarrhea in Newborn Piglets,http://dx.doi.org/10.1007/s12250-018-0003-8,PMC6178105,,,"Porcine deltacoronavirus (PDCoV) is a newly identified virus that causes watery diarrhea in newborn piglets and results in significant economic losses to the pig industry. Since first reported in Hong Kong in 2012, PDCoV has been subsequently detected in USA, South Korea, Thailand, and mainland China. Here we isolated a strain of PDCoV, named CHN-GD-2016, from the intestinal content of a diseased newborn piglet with severe diarrhea in a pig farm in Guangdong, China. PDCoV CHN-GD-2016 could be identified by immunofluorescence with PDCoV specific rabbit antisera, and typical crown-shaped particles with spiky surface projections of this PDCoV were observed with electron microscopy. Genomic analysis showed that the PDCoV CHN-GD-2016 was closely related to other Chinese PDCoV strains, with the highest sequence similarity with the strain CHN/Tianjin/2016. Importantly, inoculation of newborn piglets with 1 × 10(5) TCID(50) of CHN-GD-2016 by oral feeding successfully reproduced clear clinical symptoms, including vomiting, dehydration, and severe diarrhea in piglets. In addition, the virus RNA in rectal swabs from 1 to 7 days post inoculation was detected, macroscopic and microscopic lesions in small intestine were observed, and viral antigen was also detected in the small intestines with immunohistochemical staining. Collectively, the data show in this study confirms that PDCoV is present in Guangdong, China and is highly pathogenic in newborn piglets.",,"['Xu, Zhichao', 'Zhong, Huiling', 'Zhou, Qingfeng', 'Du, Yunping', 'Chen, Li', 'Zhang, Yun', 'Xue, Chunyi', 'Cao, Yongchang']",,,,
,PMC,Increased urinary angiotensin converting enzyme 2 and neprilysin in patients with type 2 diabetes,http://dx.doi.org/10.1152/ajprenal.00565.2017,PMC6139527,,,"Angiotensin converting enzyme 2 (ACE2) and neprilysin (NEP) are metalloproteases that are highly expressed in the renal proximal tubules. ACE2 and NEP generate renoprotective angiotensin (1–7) from angiotensin II and angiotensin I, respectively, and therefore could have a major role in chronic kidney disease (CKD). Recent data demonstrated increased urinary ACE2 in patients with diabetes with CKD and kidney transplants. We tested the hypothesis that urinary ACE2, NEP, and a disintegrin and metalloproteinase 17 (ADAM17) are increased and could be risk predictors of CKD in patients with diabetes. ACE2, NEP, and ADAM17 were investigated in 20 nondiabetics (ND) and 40 patients with diabetes with normoalbuminuria (Dnormo), microalbuminuria (Dmicro), and macroalbuminuria (Dmacro) using ELISA, Western blot, and fluorogenic and mass spectrometric-based enzyme assays. Logistic regression model was applied to predict the risk prediction. Receiver operating characteristic curves were drawn, and prediction accuracies were calculated to explore the effectiveness of ACE2 and NEP in predicting diabetes and CKD. Results demonstrated that there is no evidence of urinary ACE2 and ADAM17 in ND subjects, but both enzymes were increased in patients with diabetes, including Dnormo. Although there was no detectable plasma ACE2 activity, there was evidence of urinary and plasma NEP in all the subjects, and urinary NEP was significantly increased in Dmicro patients. NEP and ACE2 showed significant correlations with metabolic and renal characteristics. In summary, urinary ACE2, NEP, and ADAM17 are increased in patients with diabetes and could be used as early biomarkers to predict the incidence or progression of CKD at early stages among individuals with type 2 diabetes.",,"['Gutta, Sridevi', 'Grobe, Nadja', 'Kumbaji, Meenasri', 'Osman, Hassan', 'Saklayen, Mohammad', 'Li, Gengxin', 'Elased, Khalid M.']",,,,
,PMC,Measles outbreak response decision-making under uncertainty: a retrospective analysis,http://dx.doi.org/10.1098/rsif.2017.0575,PMC5908520,,,"Resurgent outbreaks of vaccine-preventable diseases that have previously been controlled or eliminated have been observed in many settings. Reactive vaccination campaigns may successfully control outbreaks but must necessarily be implemented in the face of considerable uncertainty. Real-time surveillance may provide critical information about at-risk population and optimal vaccination targets, but may itself be limited by the specificity of disease confirmation. We propose an integrated modelling approach that synthesizes historical demographic and vaccination data with real-time outbreak surveillance via a dynamic transmission model and an age-specific disease confirmation model. We apply this framework to data from the 1996–1997 measles outbreak in São Paulo, Brazil. To simulate the information available to decision-makers, we truncated the surveillance data to what would have been available at 1 or 2 months prior to the realized interventions. We use the model, fitted to real-time observations, to evaluate the likelihood that candidate age-targeted interventions could control the outbreak. Using only data available prior to the interventions, we estimate that a significant excess of susceptible adults would prevent child-targeted campaigns from controlling the outbreak and that failing to account for age-specific confirmation rates would underestimate the importance of adult-targeted vaccination.",,"['Fonnesbeck, Christopher J.', 'Shea, Katriona', 'Carran, Spencer', 'Cassio de Moraes, Jose', 'Gregory, Christopher', 'Goodson, James L.', 'Ferrari, Matthew J.']",,,,
,PMC,A Participatory System for Preventing Pandemics of Animal Origins: Pilot Study of the Participatory One Health Disease Detection (PODD) System,http://dx.doi.org/10.2196/publichealth.7375,PMC5885059,29563079,CC BY,"BACKGROUND: Aiming for early disease detection and prompt outbreak control, digital technology with a participatory One Health approach was used to create a novel disease surveillance system called Participatory One Health Disease Detection (PODD). PODD is a community-owned surveillance system that collects data from volunteer reporters; identifies disease outbreak automatically; and notifies the local governments (LGs), surrounding villages, and relevant authorities. This system provides a direct and immediate benefit to the communities by empowering them to protect themselves. OBJECTIVE: The objective of this study was to determine the effectiveness of the PODD system for the rapid detection and control of disease outbreaks. METHODS: The system was piloted in 74 LGs in Chiang Mai, Thailand, with the participation of 296 volunteer reporters. The volunteers and LGs were key participants in the piloting of the PODD system. Volunteers monitored animal and human diseases, as well as environmental problems, in their communities and reported these events via the PODD mobile phone app. LGs were responsible for outbreak control and provided support to the volunteers. Outcome mapping was used to evaluate the performance of the LGs and volunteers. RESULTS: LGs were categorized into one of the 3 groups based on performance: A (good), B (fair), and C (poor), with the majority (46%,34/74) categorized into group B. Volunteers were similarly categorized into 4 performance groups (A-D), again with group A showing the best performance, with the majority categorized into groups B and C. After 16 months of implementation, 1029 abnormal events had been reported and confirmed to be true reports. The majority of abnormal reports were sick or dead animals (404/1029, 39.26%), followed by zoonoses and other human diseases (129/1029, 12.54%). Many potentially devastating animal disease outbreaks were detected and successfully controlled, including 26 chicken high mortality outbreaks, 4 cattle disease outbreaks, 3 pig disease outbreaks, and 3 fish disease outbreaks. In all cases, the communities and animal authorities cooperated to apply community contingency plans to control these outbreaks, and community volunteers continued to monitor the abnormal events for 3 weeks after each outbreak was controlled. CONCLUSIONS: By design, PODD initially targeted only animal diseases that potentially could emerge into human pandemics (eg, avian influenza) and then, in response to community needs, expanded to cover human health and environmental health issues.",2018 Mar 21,"['Yano, Terdsak', 'Phornwisetsirikun, Somphorn', 'Susumpow, Patipat', 'Visrutaratna, Surasing', 'Chanachai, Karoon', 'Phetra, Polawat', 'Chaisowwong, Warangkhana', 'Trakarnsirinont, Pairat', 'Hemwan, Phonpat', 'Kaewpinta, Boontuan', 'Singhapreecha, Charuk', 'Kreausukon, Khwanchai', 'Charoenpanyanet, Arisara', 'Robert, Chongchit Sripun', 'Robert, Lamar', 'Rodtian, Pranee', 'Mahasing, Suteerat', 'Laiya, Ekkachai', 'Pattamakaew, Sakulrat', 'Tankitiyanon, Taweesart', 'Sansamur, Chalutwan', 'Srikitjakarn, Lertrak']",JMIR Public Health Surveill,,,
,PMC,Hyponatremia in children with pneumonia rarely means SIADH,http://dx.doi.org/10.1093/pch/pxy003,PMC6199641,,,"BACKGROUND: Hyponatremia (HN) < 135 mmol/L is a frequent finding in children with community-acquired pneumonia (CAP). We aimed to determine the proportion of syndrome of inappropriate antidiuretic hormone secretion (SIADH) among patients with CAP and HN. Moreover, we wished to investigate the relationship between HN and inflammatory markers, bacterial etiology and prognosis in hospitalized children with CAP. METHODS: We carried out a prospective, observational, multicentre, prospective cohort study. Eligible participants were children from 1 month to 17 years old hospitalized due to CAP from 2012 to 2015. RESULTS: A total of 150 children were analyzed. Forty-five (30%) patients had serum sodium levels of less than 135 mmol/L. Patients with HN had significantly higher concentrations of inflammatory biomarkers. They also had significantly lower osmolality and urine sodium. They also had longer hospitalizations and more days of fever. Only 16 out of the 45 (35%) patients with HN had confirmed calculated plasma osmolality (<275 mOsm/kg). Only 5 out of 37 (13%) patients with available measurements of plasma osmolality and urine sodium fulfilled the criteria for SIADH. Among the 16 patients with HN and hypo-osmolality, 15 had a fractional sodium excretion (EFNa) levels of less than 1%. We found a significant inverse linear correlation between serum sodium and C-reactive protein, as well as serum sodium and procalcitonin. We found a significant direct correlation between serum sodium and urine sodium. CONCLUSION: HN is a common finding in hospitalized children with CAP. True SIADH is a rare event. HN has a good correlation with inflammatory biomarkers.",,"['Tagarro, Alfredo', 'Martín, María-Dolores', 'Del-Amo, Nazaret', 'Sanz-Rosa, David', 'Rodríguez MD PhD, Mario', 'Galán MD PhD, Juan-Carlos', 'Otheo, Enrique']",,,,
,PMC,Coronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitors,http://dx.doi.org/10.1099/jgv.0.001047,PMC6537626,,,"Enveloped viruses gain entry into host cells by fusing with cellular membranes, a step that is required for virus replication. Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and infectious bronchitis virus (IBV), fuse at the plasma membrane or use receptor-mediated endocytosis and fuse with endosomes, depending on the cell or tissue type. The virus spike (S) protein mediates fusion with the host cell membrane. We have shown previously that an Abelson (Abl) kinase inhibitor, imatinib, significantly reduces SARS-CoV and MERS-CoV viral titres and prevents endosomal entry by HIV SARS S and MERS S pseudotyped virions. SARS-CoV and MERS-CoV are classified as BSL-3 viruses, which makes experimentation into the cellular mechanisms involved in infection more challenging. Here, we use IBV, a BSL-2 virus, as a model for studying the role of Abl kinase activity during coronavirus infection. We found that imatinib and two specific Abl kinase inhibitors, GNF2 and GNF5, reduce IBV titres by blocking the first round of virus infection. Additionally, all three drugs prevented IBV S-induced syncytia formation prior to the hemifusion step. Our results indicate that membrane fusion (both virus–cell and cell–cell) is blocked in the presence of Abl kinase inhibitors. Studying the effects of Abl kinase inhibitors on IBV will be useful in identifying the host cell pathways required for coronavirus infection. This will provide an insight into possible therapeutic targets to treat infections by current as well as newly emerging coronaviruses.",,"['Sisk, Jeanne M.', 'Frieman, Matthew B.', 'Machamer, Carolyn E.']",,,,
,PMC,Severe immunodeficiency associated with acute lymphoblastic leukemia and its treatment,http://dx.doi.org/10.1016/j.anai.2017.12.023,PMC5975371,,,,,"['Raje, Nikita', 'Snyder, Brenda L.', 'Hill, David A.', 'Streicher, Jenna L.', 'Sullivan, Kate E.']",,,,
,PMC,"Detection of influenza C viruses among outpatients and patients hospitalized for severe acute respiratory infection, Minnesota, 2013–2016",http://dx.doi.org/10.1093/cid/cix931,PMC5862734,,,"BACKGROUND: Existing literature suggests that influenza C typically causes mild respiratory tract disease. However, clinical and epidemiological data are limited. METHODS: Four outpatient clinics and three hospitals submitted clinical data and respiratory specimens through a surveillance network for acute respiratory infection (ARI) during May 2013 through December 2016. Specimens were tested using multi-target nucleic acid amplification tests (NAAT) for 19–22 respiratory pathogens, including influenza C. RESULTS: Influenza C virus was detected among 59 of 10,202 (0.58%) hospitalized SARI cases and 11 of 2,282 (0.48%) outpatients. Most detections occurred from December to March, with 73% during the 2014–2015 season. Influenza C detections occurred among patients of all ages, with similar rates between inpatients and outpatients. The highest rate of detection occurred among children aged 6 to 24 months (1.2%). Among hospitalized cases, seven required intensive care. Medical co-morbidities were reported in 58% of hospitalized cases and all who required intensive care. At least one other respiratory pathogen was detected in 40 (66%) cases, most commonly rhinovirus/enterovirus (25%) and respiratory syncytial virus (RSV) (20%). The hemagglutinin-esterase-fusion (HEF) gene was sequenced in 37 specimens, and both C/Kanagawa and C/Sao Paulo lineages were detected in inpatients and outpatients. CONCLUSIONS: We found seasonal circulation of influenza C with year-to-year variability. Detection was most frequent among young children, but occurred in all ages. Some cases positive for influenza C, particularly those with co-morbid conditions, had severe disease, suggesting a need for further study of the role of influenza C virus in the pathogenesis of respiratory disease.",,"['Thielen, Beth K.', 'Friedlander, Hannah', 'Bistodeau, Sarah', 'Shu, Bo', 'Lynch, Brian', 'Martin, Karen', 'Bye, Erica', 'Como-Sabetti, Kathyrn', 'Boxrud, David', 'Strain, Anna K.', 'Chaves, Sandra S.', 'Steffens, Andrea', 'Fowlkes, Ashley L.', 'Lindstrom, Stephen', 'Lynfield, Ruth']",,,,
,PMC,Rapid response to an emerging infectious disease - Lessons learned from development of a synthetic DNA vaccine targeting Zika virus,http://dx.doi.org/10.1016/j.micinf.2018.03.001,PMC6593156,,,"Vaccines are considered one of the greatest advances in modern medicine. The global burden of numerous infectious diseases has been significantly reduced, and in some cases, effectively eradicated through the deployment of specific vaccines. However, efforts to develop effective vaccines against infectious pathogens such as influenza, HIV, dengue virus (DENV), chikungunya virus (CHIKV), Ebola virus, and Zika virus (ZIKV) have proven challenging. Zika virus is a mosquito-vectored flavivirus responsible for periodic outbreaks of disease in Africa, Southeast Asia, and the Pacific Islands dating back over 50 years. Over this period, ZIKV infections were subclinical in most infected individuals and resulted in mild cases of fever, arthralgia, and rash in others. Concerns about ZIKV changed over the past two years, however, as outbreaks in Brazil, Central American countries, and Caribbean islands revealed novel aspects of infection including vertical and sexual transmission modes. Cases have been reported showing dramatic neurological pathologies including microcephaly and other neurodevelopmental problems in babies born to ZIKV infected mothers, as well as an increased risk of Guillain-Barre syndrome in adults. These findings prompted the World Health Organization to declare ZIKV a public health emergency in 2016, which resulted in expanded efforts to develop ZIKV vaccines and immunotherapeutics. Several ZIKV vaccine candidates that are immunogenic and effective at blocking ZIKV infection in animal models have since been developed, with some of these now being evaluated in the clinic. Additional therapeutics under investigation include anti-ZIKV monoclonal antibodies (mAbs) that have been shown to neutralize infection in vitro as well as protect against morbidity in mouse models of ZIKV infection. In this review, we summarize the current understanding of ZIKV biology and pathogenesis and describe our efforts to rapidly develop a vaccine against ZIKV.",,"['Kudchodkar, Sagar B.', 'Choi, Hyeree', 'Reuschel, Emma L.', 'Esquivel, Rianne', 'Kwon, Jackie Jin-Ah', 'Jeong, Moonsup', 'Maslow, Joel N.', 'Reed, Charles C.', 'White, Scott', 'Kim, J Joseph', 'Kobinger, Gary P.', 'Tebas, Pablo', 'Weiner, David B.', 'Muthumani, Kar']",,,,
,PMC,Fusion Inhibitory Lipopeptides Engineered for Prophylaxis of Nipah Virus in Primates,http://dx.doi.org/10.1093/infdis/jiy152,PMC6009590,,,"BACKGROUND: The emerging zoonotic paramyxovirus Nipah virus (NiV) causes severe respiratory and neurological disease in humans, with high fatality rates. Nipah virus can be transmitted via person-to-person contact, posing a high risk for epidemic outbreaks. However, a broadly applicable approach for human NiV outbreaks in field settings is lacking. METHODS: We engineered new antiviral lipopeptides and analyzed in vitro fusion inhibition to identify an optimal candidate for prophylaxis of NiV infection in the lower respiratory tract, and we assessed antiviral efficiency in 2 different animal models. RESULTS: We show that lethal NiV infection can be prevented with lipopeptides delivered via the respiratory route in both hamsters and nonhuman primates. By targeting retention of peptides for NiV prophylaxis in the respiratory tract, we avoid its systemic delivery in individuals who need only prevention, and thus we increase the safety of treatment and enhance utility of the intervention. CONCLUSIONS: The experiments provide a proof of concept for the use of antifusion lipopeptides for prophylaxis of lethal NiV. These results advance the goal of rational development of potent lipopeptide inhibitors with desirable pharmacokinetic and biodistribution properties and a safe effective delivery method to target NiV and other pathogenic viruses.",,"['Mathieu, Cyrille', 'Porotto, Matteo', 'Figueira, Tiago N', 'Horvat, Branka', 'Moscona, Anne']",,,,
,PMC,Ubiquitination regulation of inflammatory responses through NF-κB pathway,,PMC5883129,,,"The development of inflammation is mutually affected with damaged DNA and the abnormal expression of protein modification. Ubiquitination, a way of protein modification, plays a key role in regulating various biological functions including inflammation responses. The ubiquitin enzymes and deubiquitinating enzymes (DUBs) jointly control the ubiquitination. The fact that various ubiquitin linkage chains control the fate of the substrate suggests that the regulatory mechanisms of ubiquitin enzymes are central for ubiquitination. In inflammation diseases, the pro-inflammatory transcription factor NF-κB regulates transcription of pro-labour mediators in response to inflammatory stimuli and expression of numerous genes that control inflammation which is associated with ubiquitination. The ubiquitination regulates NF-κB signaling pathway with many receptor families, including NOD-like receptors (NLR), Toll-like receptors (TLR) and RIG-I-like receptors (RLR), mainly by K63-linked polyubiquitin chains. In this review, we highlight the study of ubiquitination in the inflammatory signaling pathway including NF-κB signaling regulated by ubiquitin enzymes and DUBs. Furthermore, it is emphasized that the interaction of ubiquitin-mediated inflammatory signaling system accurately regulates the inflammatory responses.",,"['Wu, Yunbing', 'Kang, Jingjing', 'Zhang, Lu', 'Liang, Zhaofeng', 'Tang, Xudong', 'Yan, Yongmin', 'Qian, Hui', 'Zhang, Xu', 'Xu, Wenrong', 'Mao, Fei']",,,,
,PMC,Enhancement of safety and immunogenicity of the Chinese Hu191 measles virus vaccine by alteration of the S-adenosylmethionine (SAM) binding site in the large polymerase protein,http://dx.doi.org/10.1016/j.virol.2018.02.022,PMC6413878,,,"The live-attenuated measles virus (MV) vaccine based on the Hu191 strain has played a significant role in controlling measles in China. However, it has considerable adverse effects that may cause public health burden. We hypothesize that the safety and efficacy of MV vaccine can be improved by altering the S-adeno- sylmethionine (SAM) binding site in the conserved region VI of the large polymerase protein. To test this hypothesis, we established an efficient reverse genetics system for the rMV-Hu191 strain and generated two recombinant MV-Hu191 carrying mutations in the SAM binding site. These two mutants grew to high titer in Vero cells, were genetically stable, and were significantly more attenuated in vitro and in vivo compared to the parental rMV-Hu191 vaccine strain. Importantly, both MV-Hu191 mutants triggered a higher neutralizing antibody than rMV-Hu191 vaccine and provided complete protection against MV challenge. These results demonstrate its potential for an improved MV vaccine candidate.",,"['Wang, Yilong', 'Liu, Rongxian', 'Lu, Mijia', 'Yang, Yingzhi', 'Zhou, Duo', 'Hao, Xiaoqiang', 'Zhou, Dongming', 'Wang, Bin', 'Li, Jianrong', 'Huang, Yao-Wei', 'Zhao, Zhengyan']",,,,
,PMC,Exploring political influences on evidence-based non-communicable disease prevention across four countries,http://dx.doi.org/10.1093/her/cyy005,PMC6279167,,,"Implementation of evidence-based practices can improve efficiency and effectiveness of public health efforts. Few studies have explored the political contextual factors that impact implementation of evidence-based non-communicable disease prevention (EBNCDP). This study aimed to do so in Australia, Brazil, China and the United States. Investigators conducted 10–13 qualitative, semi-structured interviews of public health practitioners working in functionally similar public health organizations in each country (total N = 50). Study participants were identified through purposive sampling and interviews were structured around an interview guide covering six domains related to EBNCDP. Interviewees from all four countries identified funding as the primary politically-influenced barrier to implementing EBNCDP. Similarly widespread barriers included government funding priorities that shift based on who is in power and the difficulty of convincing policy-makers and funders that non-communicable disease prevention is a wise investment of political capital. Policymakers who are not evidence-driven was another common barrier even in the United States and Australia, where EBNCDP is more established. Findings suggest that political contextual factors influence EBNCDP and vary to an extent by country, though certain factors seem to be universal. This can aid public health practitioners, political leaders, and policymakers in advocating for conditions and policies that encourage evidence-based practice.",,"['Furtado, Karishma S', 'Budd, Elizabeth L', 'Ying, Xiangji', 'deRuyter, Anna J', 'Armstrong, Rebecca L', 'Pettman, Tahna L', 'Reis, Rodrigo S', 'Sung-Chan, Pauline', 'Wang, Zhaoxin', 'Saunders, Tahnee', 'Becker, Leonardo A', 'Shi, Jianwei', 'Mui, Long Sum Tabitha', 'Brownson, Ross C']",,,,
,PMC,Dengue Virus Selectively Annexes Endoplasmic Reticulum-Associated Translation Machinery as a Strategy for Co-opting Host Cell Protein Synthesis,http://dx.doi.org/10.1128/JVI.01766-17,PMC5972907,,,"A primary question in dengue virus (DENV) biology is the molecular strategy for recruitment of host cell protein synthesis machinery. Here, we combined cell fractionation, ribosome profiling, and transcriptome sequencing (RNA-seq) to investigate the subcellular organization of viral genome translation and replication as well as host cell translation and its response to DENV infection. We report that throughout the viral life cycle, DENV plus- and minus-strand RNAs were highly partitioned to the endoplasmic reticulum (ER), identifying the ER as the primary site of DENV translation. DENV infection was accompanied by an ER compartment-specific remodeling of translation, where ER translation capacity was subverted from host transcripts to DENV plus-strand RNA, particularly at late stages of infection. Remarkably, translation levels and patterns in the cytosol compartment were only modestly affected throughout the experimental time course of infection. Comparisons of ribosome footprinting densities of the DENV plus-strand RNA and host mRNAs indicated that DENV plus-strand RNA was only sparsely loaded with ribosomes. Combined, these observations suggest a mechanism where ER-localized translation and translational control mechanisms, likely cis encoded, are used to repurpose the ER for DENV virion production. Consistent with this view, we found ER-linked cellular stress response pathways commonly associated with viral infection, namely, the interferon response and unfolded protein response, to be only modestly activated during DENV infection. These data support a model where DENV reprograms the ER protein synthesis and processing environment to promote viral survival and replication while minimizing the activation of antiviral and proteostatic stress response pathways. IMPORTANCE DENV, a prominent human health threat with no broadly effective or specific treatment, depends on host cell translation machinery for viral replication, immune evasion, and virion biogenesis. The molecular mechanism by which DENV commandeers the host cell protein synthesis machinery and the subcellular organization of DENV replication and viral protein synthesis is poorly understood. Here, we report that DENV has an almost exclusively ER-localized life cycle, with viral replication and translation largely restricted to the ER. Surprisingly, DENV infection largely affects only ER-associated translation, with relatively modest effects on host cell translation in the cytosol. DENV RNA translation is very inefficient, likely representing a strategy to minimize disruption of ER proteostasis. Overall these findings demonstrate that DENV has evolved an ER-compartmentalized life cycle; thus, targeting the molecular signatures and regulation of the DENV-ER interaction landscape may reveal strategies for therapeutic intervention.",,"['Reid, David W.', 'Campos, Rafael K.', 'Child, Jessica R.', 'Zheng, Tianli', 'Chan, Kitti Wing Ki', 'Bradrick, Shelton S.', 'Vasudevan, Subhash G.', 'Garcia-Blanco, Mariano A.', 'Nicchitta, Christopher V.']",,,,
,PMC,ERK Is a Critical Regulator of JC Polyomavirus Infection,http://dx.doi.org/10.1128/JVI.01529-17,PMC5972906,,,"The human JC polyomavirus (JCPyV) infects the majority of the population worldwide and presents as an asymptomatic, persistent infection in the kidneys. In individuals who are immunocompromised, JCPyV can become reactivated and cause a lytic infection in the central nervous system resulting in the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). Infection is initiated by interactions between the capsid protein viral protein 1 (VP1) and the α2,6-linked sialic acid on lactoseries tetrasaccharide c (LSTc), while JCPyV internalization is facilitated by 5-hydroxytryptamine 2 receptors (5-HT(2)Rs). The mechanisms by which the serotonin receptors mediate virus entry and the signaling cascades required to drive viral infection remain poorly understood. JCPyV was previously shown to induce phosphorylation of extracellular signal-regulated kinase (ERK), a downstream target of the mitogen-activated protein kinase (MAPK) pathway, upon virus entry. However, it remained unclear whether ERK activation was required for JCPyV infection. Both ERK-specific small interfering RNA (siRNA) and ERK inhibitor treatments resulted in significantly diminished JCPyV infection in both kidney and glial cells yet had no effect on the infectivity of the polyomavirus simian virus 40 (SV40). Experiments characterizing the role of ERK during steps in the viral life cycle indicate that ERK activation is required for viral transcription, as demonstrated by a significant reduction in production of large T antigen (TAg), a key viral protein associated with the initiation of viral transcription and viral replication. These findings delineate the role of the MAPK-ERK signaling pathway in JCPyV infection, elucidating how the virus reprograms the host cell to promote viral pathogenesis. IMPORTANCE Viral infection is dependent upon host cell factors, including the activation of cellular signaling pathways. These interactions between viruses and host cells are necessary for infection and play an important role in viral disease outcomes. The focus of this study was to determine how the human JC polyomavirus (JCPyV), a virus that resides in the kidney of the majority of the population and can cause the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML) in the brains of immunosuppressed individuals, usurps a cellular signaling pathway to promote its own infectious life cycle. We demonstrated that the activation of extracellular signal-regulated kinase (ERK), a component of the mitogen-activated protein kinase (MAPK) pathway, promotes JCPyV transcription, which is required for viral infection. Our findings demonstrate that the MAPK-ERK signaling pathway is a key determinant of JCPyV infection, elucidating new information regarding the signal reprogramming of host cells by a pathogenic virus.",,"['DuShane, Jeanne K.', 'Wilczek, Michael P.', 'Mayberry, Colleen L.', 'Maginnis, Melissa S.']",,,,
,PMC,Two Residues in NSP9 Contribute to the Enhanced Replication and Pathogenicity of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1128/JVI.02209-17,PMC5972891,,,"Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) possesses greater replicative capacity and pathogenicity than classical PRRSV. However, the factors that lead to enhanced replication and pathogenicity remain unclear. In our study, an alignment of all available full-length sequences of North American-type PRRSVs (n = 204) revealed two consistent amino acid mutations that differed between HP-PRRSV and classical PRRSV and were located at positions 519 and 544 in nonstructural protein 9. Next, a series of mutant viruses with either single or double amino acid replacements were generated from HP-PRRSV HuN4 and classical PRRSV CH-1a infectious cDNA clones. Deletion of either of the amino acids led to a complete loss of virus viability. In both Marc-145 and porcine alveolar macrophages, the replicative efficiencies of mutant viruses based on HuN4 were reduced compared to the parent, whereas the replication level of CH-1a-derived mutant viruses was increased. Plaque growth assays showed clear differences between mutant and parental viruses. In infected piglets, the pathogenicity of HuN4-derived mutant viruses, assessed through clinical symptoms, viral load in sera, histopathology examination, and thymus atrophy, was reduced. Our results indicate that the amino acids at positions 519 and 544 in NSP9 are involved in the replication efficiency of HP-PRRSV and contribute to enhanced pathogenicity. This study is the first to identify specific amino acids involved in PRRSV replication or pathogenicity. These findings will contribute to understanding the molecular mechanisms of PRRSV replication and pathogenicity, leading to better therapeutic and prognostic options to combat the virus. IMPORTANCE Porcine reproductive and respiratory syndrome (PRRS), caused by porcine reproductive and respiratory syndrome virus (PRRSV), is a significant threat to the global pig industry. Highly pathogenic PRRSV (HP-PRRSV) first emerged in China in 2006 and has subsequently spread across Asia, causing considerable damage to local economies. HP-PRRSV strains possess a greater replication capacity and higher pathogenicity than classical PRRSV strains, although the mechanisms that underlie these characteristics are unclear. In the present study, we identified two mutations in HP-PRRSV strains that distinguish them from classical PRRSV strains. Further experiments that swapped the two mutations in an HP-PRRSV strain and a classical PRRSV strain demonstrated that they are involved in the replication efficiency of the virus and its virulence. Our findings have important implications for understanding the molecular mechanisms of PRRSV replication and pathogenicity and also provide new avenues of research for the study of other viruses.",,"['Zhao, Kuan', 'Gao, Jia-Cong', 'Xiong, Jun-Yao', 'Guo, Jin-Chao', 'Yang, Yong-Bo', 'Jiang, Cheng-Gang', 'Tang, Yan-Dong', 'Tian, Zhi-Jun', 'Cai, Xue-Hui', 'Tong, Guang-Zhi', 'An, Tong-Qing']",,,,
,PMC,Identification of Poxvirus Genome Uncoating and DNA Replication Factors with Mutually Redundant Roles,http://dx.doi.org/10.1128/JVI.02152-17,PMC5972866,,,"Genome uncoating is essential for replication of most viruses. For poxviruses, the process is divided into two stages: removal of the envelope, allowing early gene expression, and breaching of the core wall, allowing DNA release, replication, and late gene expression. Subsequent studies showed that the host proteasome and the viral D5 protein, which has an essential role in DNA replication, are required for vaccinia virus (VACV) genome uncoating. In a search for additional VACV uncoating proteins, we noted a report that described a defect in DNA replication and late expression when the gene encoding a 68-kDa ankyrin repeat/F-box protein (68k-ank), associated with the cellular SCF (Skp1, cullin1, F-box-containing complex) ubiquitin ligase complex, was deleted from the attenuated modified vaccinia virus Ankara (MVA). Here we showed that the 68k-ank deletion mutant exhibited diminished genome uncoating, formation of DNA prereplication sites, and degradation of viral cores as well as an additional, independent defect in DNA synthesis. Deletion of the 68k-ank homolog of VACV strain WR, however, was without effect, suggesting the existence of compensating genes. By inserting VACV genes into an MVA 68k-ank deletion mutant, we discovered that M2, a member of the poxvirus immune evasion (PIE) domain superfamily and a regulator of NF-κB, and C5, a member of the BTB/Kelch superfamily associated with cullin-3-based ligase complexes, independently rescued the 68k-ank deletion phenotype. Thus, poxvirus uncoating and DNA replication are intertwined processes involving at least three viral proteins with mutually redundant functions in addition to D5. IMPORTANCE Poxviruses comprise a family of large DNA viruses that infect vertebrates and invertebrates and cause diseases of medical and zoological importance. Poxviruses, unlike most other DNA viruses, replicate in the cytoplasm, and their large genomes usually encode 200 or more proteins with diverse functions. About 90 genes may be essential for chordopoxvirus replication based either on their conservation or individual gene deletion studies. However, this number may underestimate the true number of essential functions because of redundancy. Here we show that any one of three seemingly unrelated and individually nonessential proteins is required for the incompletely understood processes of genome uncoating and DNA replication, an example of synthetic lethality. Thus, poxviruses appear to have a complex genetic interaction network that has not been fully appreciated and which will require multifactor deletion screens to assess.",,"['Liu, Baoming', 'Panda, Debasis', 'Mendez-Rios, Jorge D.', 'Ganesan, Sundar', 'Wyatt, Linda S.', 'Moss, Bernard']",,,,
,PMC,Emergency Services of Viral RNAs: Repair and Remodeling,http://dx.doi.org/10.1128/MMBR.00067-17,PMC5968460,,,"Reproduction of RNA viruses is typically error-prone due to the infidelity of their replicative machinery and the usual lack of proofreading mechanisms. The error rates may be close to those that kill the virus. Consequently, populations of RNA viruses are represented by heterogeneous sets of genomes with various levels of fitness. This is especially consequential when viruses encounter various bottlenecks and new infections are initiated by a single or few deviating genomes. Nevertheless, RNA viruses are able to maintain their identity by conservation of major functional elements. This conservatism stems from genetic robustness or mutational tolerance, which is largely due to the functional degeneracy of many protein and RNA elements as well as to negative selection. Another relevant mechanism is the capacity to restore fitness after genetic damages, also based on replicative infidelity. Conversely, error-prone replication is a major tool that ensures viral evolvability. The potential for changes in debilitated genomes is much higher in small populations, because in the absence of stronger competitors low-fit genomes have a choice of various trajectories to wander along fitness landscapes. Thus, low-fit populations are inherently unstable, and it may be said that to run ahead it is useful to stumble. In this report, focusing on picornaviruses and also considering data from other RNA viruses, we review the biological relevance and mechanisms of various alterations of viral RNA genomes as well as pathways and mechanisms of rehabilitation after loss of fitness. The relationships among mutational robustness, resilience, and evolvability of viral RNA genomes are discussed.",,"['Agol, Vadim I.', 'Gmyl, Anatoly P.']",,,,
,PMC,"Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development",http://dx.doi.org/10.1152/physrev.00025.2017,PMC6050347,,,"This review focuses on one family of the known cAMP receptors, the exchange proteins directly activated by cAMP (EPACs), also known as the cAMP-regulated guanine nucleotide exchange factors (cAMP-GEFs). Although EPAC proteins are fairly new additions to the growing list of cAMP effectors, and relatively “young” in the cAMP discovery timeline, the significance of an EPAC presence in different cell systems is extraordinary. The study of EPACs has considerably expanded the diversity and adaptive nature of cAMP signaling associated with numerous physiological and pathophysiological responses. This review comprehensively covers EPAC protein functions at the molecular, cellular, physiological, and pathophysiological levels; and in turn, the applications of employing EPAC-based biosensors as detection tools for dissecting cAMP signaling and the implications for targeting EPAC proteins for therapeutic development are also discussed.",,"['Robichaux, William G.', 'Cheng, Xiaodong']",,,,
,PMC,Evaluation of Antibody-Dependent Enhancement of SARS-CoV Infection in Rhesus Macaques Immunized with an Inactivated SARS-CoV Vaccine,http://dx.doi.org/10.1007/s12250-018-0009-2,PMC6178114,,,,,"['Luo, Fan', 'Liao, Fan-Lu', 'Wang, Hui', 'Tang, Hong-Bin', 'Yang, Zhan-Qiu', 'Hou, Wei']",,,,
,PMC,Analytical Performance of a Loop-Mediated Isothermal Amplification Assay for Leishmania DNA Detection in Sandflies and Direct Smears of Patients with Cutaneous Leishmaniasis,http://dx.doi.org/10.4269/ajtmh.17-0808,PMC5953379,,,"Loop-mediated isothermal amplification (LAMP) is ideal for the detection of Leishmania DNA as it is a quick and easy-to-perform test that does not require complex or sophisticated equipment or infrastructure. However, the application of this technique in the detection of Leishmania DNA has not been comprehensively analyzed to date (analytical validation). Our objective was to evaluate the sensitivity and analytical specificity (anticipated reportable range [ARR], the limit of detection [LoD], and accuracy) of LAMP targeting the 18S rRNA gene in the diagnosis of six New World Leishmania species. We then applied the validated LAMP assay across 50 samples of sandflies and 50 direct smears from a recent outbreak of cutaneous leishmaniasis in Colombia to determine its diagnostic performance. The LAMP assay exclusively amplified the DNA of Leishmania spp., and an ARR of between 1 × 10(4) and 1 × 10(−2) equivalent parasites/mL was determined. An LoD of 1 × 10(−2) equivalent parasites/mL was established and there was no statistically significant variation in terms of accuracy. Finally, a sensitivity of 100% in direct smears and sandflies samples was calculated and a specificity of 90.9% for direct smears using microscopy as reference and 96.8% for sandflies using real-time polymerase chain reaction as reference were determined. To our knowledge, this is the first attempt to analytically validate a LAMP test to detect Leishmania DNA, which showed good diagnostic potential from sandflies and direct smear samples.",,"['León, Cielo M.', 'Muñoz, Marina', 'Tabares, Juan H.', 'Hernandez, Carolina', 'Florez, Carolina', 'Ayala, Martha S.', 'Ramírez, Juan David']",,,,
,PMC,"MicroRNA-192 inhibits the proliferation, migration and invasion of osteosarcoma cells and promotes apoptosis by targeting matrix metalloproteinase-11",http://dx.doi.org/10.3892/ol.2018.8239,PMC5920878,,,"MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression during stem cell growth, proliferation and differentiation. miRNAs are also involved in the development and progression of a number of cancer types, including osteosarcoma (OS). miR-192 is significantly downregulated in various tumors, including lung, bladder and rectal cancer. miR-192 expression is associated with the migration and invasion of OS cells. However, the expression of miR-192 and its effects on the development of OS have not been reported. In the present study, the involvement of miR-192 and its molecular mechanisms in the development of OS was investigated. The results indicate that miR-192 expression was significantly downregulated in OS tissues compared with non-tumor tissues (P<0.05). Next, a miR-192 agomir was transfected into the OS cell line MG-63 to upregulate miR-192. The effects of miR-192 overexpression were then investigated by examining cell proliferation, apoptosis, migration and invasion. Matrix metalloproteinase (MMP)-11 belongs to a family of nine or more highly homologous Zn(2+)-endopeptidases. It was demonstrated that the mRNA and protein expression of MMP-11 were upregulated in OS tissues compared with non-tumor tissues (P<0.05). MMP-11 was predicted by TargetScan and miRanda as a miR-192 target, which was confirmed by western blotting and dual-luciferase assays. Finally, it was demonstrated that the overexpression of miR-192 was able to downregulate MMP-11 expression and reduce proliferation, migration and invasion, and promote apoptosis in OS cells. Together, these data indicate that miR-192 may be a tumor suppressor that inhibits the progression and invasion of OS by targeting MMP-11. Therefore, miR-192 may be useful for the diagnosis and treatment of OS.",,"['Shang, Guowei', 'Mi, Yang', 'Mei, Yingwu', 'Wang, Guanghui', 'Wang, Yadong', 'Li, Xinjie', 'Wang, Yisheng', 'Li, Yuebai', 'Zhao, Guoqiang']",,,,
,PMC,Responses of migratory species and their pathogens to supplemental feeding,http://dx.doi.org/10.1098/rstb.2017.0094,PMC5883000,,,"Migratory animals undergo seasonal and often spectacular movements and perform crucial ecosystem services. In response to anthropogenic changes, including food subsidies, some migratory animals are now migrating shorter distances or halting migration altogether and forming resident populations. Recent studies suggest that shifts in migratory behaviour can alter the risk of infection for wildlife. Although migration is commonly assumed to enhance pathogen spread, for many species, migration has the opposite effect of lowering infection risk, if animals escape from habitats where pathogen stages have accumulated or if strenuous journeys cull infected hosts. Here, we summarize responses of migratory species to supplemental feeding and review modelling and empirical work that provides support for mechanisms through which resource-induced changes in migration can alter pathogen transmission. In particular, we focus on the well-studied example of monarch butterflies and their protozoan parasites in North America. We also identify areas for future research, including combining new technologies for tracking animal movements with pathogen surveillance and exploring potential evolutionary responses of hosts and pathogens to changing movement patterns. Given that many migratory animals harbour pathogens of conservation concern and zoonotic potential, studies that document ongoing shifts in migratory behaviour and infection risk are vitally needed. This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife’.",,"['Satterfield, Dara A.', 'Marra, Peter P.', 'Sillett, T. Scott', 'Altizer, Sonia']",,,,
,PMC,Atrial myxoma presenting as infective endocarditis,http://dx.doi.org/10.1136/bcr-2017-223656,PMC5847994,,,"A 23-year-old Asian student presented to our service with a 1-month history of fever, weight loss of 10 kg, night sweats, fatigue and general malaise. He was previously well with no significant medical or family history. He had a low-grade pyrexia and cardiac auscultation revealed a diastolic murmur consistent with ‘tumour plop’. He had no sequelae of endocarditis. He had low-grade pyrexia of 37.7°C, and ECG showed sinus tachycardia at 130 bpm. He had raised inflammatory markers and was started on broad spectrum antibiotics. Blood cultures grew Streptococcus viridans twice. Transthoracic and transo-oesophageal echocardiography revealed a large mobile mass attached to the interatrial septum, suspicious for atrial myxoma, flopping into the left ventricle but not causing left ventricular outflow tract obstruction. All valves looked normal in appearance. He was treated with antibiotics for 2 weeks until inflammatory markers normalised. The patient was referred for cardiothoracic surgery where a large atrial myxoma (5 cm×3 cm) was excised just superior to the mitral valve. It had areas of necrosis and was colonised with S. viridans. He had an unremarkable postoperative course and made a complete recovery.",,"['Fitzgerald, Gerald Paul', 'Coughlan, John Joseph', 'Satti, Zahir', 'Arnous, Samer']",,,,
,PMC,Impact of PRRSV infection and dietary soybean meal on ileal amino acid digestibility and endogenous amino acid losses in growing pigs(),http://dx.doi.org/10.1093/jas/sky093,PMC6140837,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant disease in the swine industry, and increasing soybean meal (SBM) consumption during this disease challenge may improve performance. Our objectives were to determine the impact of SBM level on apparent total tract (ATTD) and ileal (AID) digestibility during PRRSV infection and to determine ileal basal endogenous losses (BEL) during PRRSV infection. Forty PRRSV negative gilts were fitted with a T-cannula in the distal ileum. Treatments were arranged in a 2 × 2 factorial with high and low SBM (HSBM, 29% vs. LSBM, 10%), with and without PRRSV (n = 6/treatment). The remaining pigs (n = 8/challenge status) were fed a N-free diet. Chromic oxide was used as an indigestible marker. On day post inoculation (dpi) 0, at 47.7 ± 0.57 kg BW, 20 pigs were inoculated with live PRRSV; 20 control pigs were sham inoculated. Infection was confirmed by serum PCR. Feces were collected at dpi 5 to 6 and dpi 16 to 17, and ileal digesta collected at dpi 7 to 8 and dpi 18 to 19. Feed, feces, and digesta were analyzed for DM, N, and GE. Digesta and feed were analyzed for AA. Data were analyzed in a 2 × 2 + 2 factorial design to determine main effects of diet and PRRSV and their interaction. Data from N-free fed pigs were analyzed separately to determine BEL and hindgut disappearance due to PRRSV infection. All control pigs remained PRRSV negative. There were no interactions for AID of AA; however, HSBM reduced DM, GE, Lys, and Met AID and increased Arg and Gly AID during both collection periods (P < 0.05). At dpi 7 to 8 only, PRRSV reduced DM and GE AID (P < 0.05). At 7 to 8 dpi, BEL of Arg, Ala, and Pro were reduced (P < 0.05) due to PRRSV by 64%, 39%, and 94%, respectively. At dpi 18 to 19, BEL of Thr tended (P = 0.06) to be increased in PRRSV-infected pigs; however, no other differences were observed. Pigs fed LSBM had increased Lys, Met, Thr, Trp, and Pro standardized ileal digestibility (SID), primarily at 7 to 8 dpi. At 7 to 8 dpi, PRRSV reduced Arg, Gly, and Pro SID (P < 0.01), and SID Pro continued to be reduced by 17% at dpi 18 to 19. Compared with HSBM pigs, LSBM reduced hindgut disappearance of DM and GE at dpi 5 to 8 and dpi 16 to 19, while N disappearance was reduced at dpi 5 to 8. There were no differences between control and PRRSV N-free fed pigs. Altogether, SBM inclusion impacts SID of AA and hindgut disappearance of nutrients, regardless of PRRSV. In contrast, there is minimal impact of PRRSV on BEL, and therefore, SID of most AA are not different.",,"['Schweer, Wesley P', 'Patience, John F', 'Burrough, Eric R', 'Kerr, Brian J', 'Gabler, Nicholas K']",,,,
,PMC,Structure–function analyses of a stereotypic rheumatoid factor unravel the structural basis for germline-encoded antibody autoreactivity,http://dx.doi.org/10.1074/jbc.M117.814475,PMC5936827,,,"Rheumatoid factors (RFs) are autoantibodies against the fragment-crystallizable (Fc) region of IgG. In individuals with hematological diseases such as cryoglobulinemia and certain B cell lymphoma forms, the RFs derived from specific heavy- and light-chain germline pairs, so-called “stereotypic RFs,” are frequently produced in copious amounts and form immune complexes with IgG in serum. Of note, many structural details of the antigen recognition mechanisms in RFs are unclear. Here we report the crystal structure of the RF YES8c derived from the IGHV1-69/IGKV3-20 germline pair, the most common of the stereotypic RFs, in complex with human IgG1-Fc at 2.8 Å resolution. We observed that YES8c binds to the CH2–CH3 elbow in the canonical antigen-binding manner involving a large antigen–antibody interface. On the basis of this observation, combined with mutational analyses, we propose a recognition mechanism common to IGHV1-69/IGKV3-20 RFs: (1) the interaction of the Leu(432)–His(435) region of Fc enables the highly variable complementarity-determining region (CDR)-H3 to participate in the binding, (2) the hydrophobic tip in the CDR-H2 typical of IGHV1-69 antibodies recognizes the hydrophobic patch on Fc, and (3) the interaction of the highly conserved RF light chain with Fc is important for RF activity. These features may determine the putative epitope common to the IGHV1-69/IGKV3-20 RFs. We also showed that some mutations in the binding site of RF increase the affinity to Fc, which may aggravate hematological diseases. Our findings unravel the structural basis for germline-encoded antibody autoreactivity.",,"['Shiroishi, Mitsunori', 'Ito, Yuji', 'Shimokawa, Kenta', 'Lee, Jae Man', 'Kusakabe, Takahiro', 'Ueda, Tadashi']",,,,
,PMC,Investigation of Viral Pathogen Profiles in Some Natural Hosts and Vectors in China,http://dx.doi.org/10.1007/s12250-018-0021-6,PMC6178075,,,,,"Yuan, Zhiming",,,,
,PMC,Characterizing the phylogenetic specialism–generalism spectrum of mammal parasites,http://dx.doi.org/10.1098/rspb.2017.2613,PMC5879627,,,"The distribution of parasites across mammalian hosts is complex and represents a differential ability or opportunity to infect different host species. Here, we take a macroecological approach to investigate factors influencing why some parasites show a tendency to infect species widely distributed in the host phylogeny (phylogenetic generalism) while others infect only closely related hosts. Using a database on over 1400 parasite species that have been documented to infect up to 69 terrestrial mammal host species, we characterize the phylogenetic generalism of parasites using standard effect sizes for three metrics: mean pairwise phylogenetic distance (PD), maximum PD and phylogenetic aggregation. We identify a trend towards phylogenetic specialism, though statistically host relatedness is most often equivalent to that expected from a random sample of host species. Bacteria and arthropod parasites are typically the most generalist, viruses and helminths exhibit intermediate generalism, and protozoa are on average the most specialist. While viruses and helminths have similar mean pairwise PD on average, the viruses exhibit higher variation as a group. Close-contact transmission is the transmission mode most associated with specialism. Most parasites exhibiting phylogenetic aggregation (associating with discrete groups of species dispersed across the host phylogeny) are helminths and viruses.",,"['Park, A. W.', 'Farrell, M. J.', 'Schmidt, J. P.', 'Huang, S.', 'Dallas, T. A.', 'Pappalardo, P.', 'Drake, J. M.', 'Stephens, P. R.', 'Poulin, R.', 'Nunn, C. L.', 'Davies, T. J.']",,,,
,PMC,Structure-Guided Design of Potent and Permeable Inhibitors of MERS Coronavirus 3CL Protease that Utilize a Piperidine Moiety as a Novel Design Element,http://dx.doi.org/10.1016/j.ejmech.2018.03.004,PMC5891363,,,"There are currently no approved vaccines or small molecule therapeutics available for the prophylaxis or treatment of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infections. MERS-CoV 3CL protease is essential for viral replication; consequently, it is an attractive target that provides a potentially effective means of developing small molecule therapeutics for combatting MERS-CoV. We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties. The mechanism of action of the compounds and the structural determinants associated with binding were illuminated using X-ray crystallography.",,"['Galasiti Kankanamalage, Anushka C.', 'Kim, Yunjeong', 'Damalanka, Vishnu C.', 'Rathnayake, Athri D.', 'Fehr, Anthony R.', 'Mehzabeen, Nurjahan', 'Battaile, Kevin P.', 'Lovell, Scott', 'Lushington, Gerald H.', 'Perlman, Stanley', 'Chang, Kyeong-Ok', 'Groutas, William C.']",,,,
,PMC,Nociceptor sensory neurons suppress neutrophil and ᵞδ T cell responses in bacterial lung infections and lethal pneumonia,http://dx.doi.org/10.1038/nm.4501,PMC6263165,,,"Lung-innervating nociceptor sensory neurons detect noxious or harmful stimuli and consequently protect organisms by mediating coughing, pain, and bronchoconstriction. However, the role of sensory neurons in pulmonary host defense is unclear. Here, we found that TRPV1(+) nociceptors suppressed protective immunity against lethal Staphylococcus aureus pneumonia. Targeted TRPV1(+)-neuron ablation increased survival, cytokine induction, and lung bacterial clearance. Nociceptors suppressed the recruitment and surveillance of neutrophils, and altered lung ᵞδ T cell numbers, which are necessary for immunity. Vagal ganglia TRPV1(+) afferents mediated immunosuppression through release of the neuropeptide calcitonin gene–related peptide (CGRP). Targeting neuroimmunological signaling may be an effective approach to treat lung infections and bacterial pneumonia.",,"['Baral, Pankaj', 'Umans, Benjamin D', 'Li, Lu', 'Wallrapp, Antonia', 'Bist, Meghna', 'Kirschbaum, Talia', 'Wei, Yibing', 'Zhou, Yan', 'Kuchroo, Vijay K', 'Burkett, Patrick R', 'Yipp, Bryan G', 'Liberles, Stephen D', 'Chiu, Isaac M']",,,,
,PMC,Chevrier’s Field Mouse (Apodemus chevrieri) and Père David’s Vole (Eothenomys melanogaster) in China Carry Orthohepeviruses that form Two Putative Novel Genotypes Within the Species Orthohepevirus C,http://dx.doi.org/10.1007/s12250-018-0011-8,PMC6178085,,,"Hepatitis E virus (HEV) is the prototype of the family Hepeviridae and the causative agent of common acute viral hepatitis. Genetically diverse HEV-related viruses have been detected in a variety of mammals and some of them may have zoonotic potential. In this study, we tested 278 specimens collected from seven wild small mammal species in Yunnan province, China, for the presence and prevalence of orthohepevirus by broad-spectrum reverse transcription (RT)-PCR. HEV-related sequences were detected in two rodent species, including Chevrier’s field mouse (Apodemus chevrieri, family Muridae) and Père David’s vole (Eothenomys melanogaster, family Cricetidae), with the infection rates of 29.20% (59/202) and 7.27% (4/55), respectively. Further four representative full-length genomes were generated: two each from Chevrier’s field mouse (named RdHEVAc14 and RdHEVAc86) and Père David’s vole (RdHEVEm40 and RdHEVEm67). Phylogenetic analyses and pairwise distance comparisons of whole genome sequences and amino acid sequences of the gene coding regions showed that orthohepeviruses identified in Chinese Chevrier’s field mouse and Père David’s vole belonged to the species Orthohepevirus C but were highly divergent from the two assigned genotypes: HEV-C1 derived from rat and shrew, and HEV-C2 derived from ferret and possibly mink. Quantitative real-time RT-PCR demonstrated that these newly discovered orthohepeviruses had hepatic tropism. In summary, our work discovered two putative novel genotypes orthohepeviruses preliminarily named HEV-C3 and HEV-C4 within the species Orthohepevirus C, which expands our understanding of orthohepevirus infection in the order Rodentia and gives new insights into the origin, evolution, and host range of orthohepevirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-018-0011-8) contains supplementary material, which is available to authorized users.",,"['Wang, Bo', 'Li, Wen', 'Zhou, Ji-Hua', 'Li, Bei', 'Zhang, Wei', 'Yang, Wei-Hong', 'Pan, Hong', 'Wang, Li-Xia', 'Bock, C. Thomas', 'Shi, Zheng-Li', 'Zhang, Yun-Zhi', 'Yang, Xing-Lou']",,,,
,PMC,"Longitudinal Surveillance of Betacoronaviruses in Fruit Bats in Yunnan Province, China During 2009–2016",http://dx.doi.org/10.1007/s12250-018-0017-2,PMC6178081,,,"Previous studies indicated that fruit bats carry two betacoronaviruses, BatCoV HKU9 and BatCoV GCCDC1. To investigate the epidemiology and genetic diversity of these coronaviruses, we conducted a longitudinal surveillance in fruit bats in Yunnan province, China during 2009–2016. A total of 59 (10.63%) bat samples were positive for the two betacorona-viruses, 46 (8.29%) for HKU9 and 13 (2.34%) for GCCDC1, or closely related viruses. We identified a novel HKU9 strain, tentatively designated as BatCoV HKU9-2202, by sequencing the full-length genome. The BatCoV HKU9-2202 shared 83% nucleotide identity with other BatCoV HKU9 stains based on whole genome sequences. The most divergent region is in the spike protein, which only shares 68% amino acid identity with BatCoV HKU9. Quantitative PCR revealed that the intestine was the primary infection organ of BatCoV HKU9 and GCCDC1, but some HKU9 was also detected in the heart, kidney, and lung tissues of bats. This study highlights the importance of virus surveillance in natural reservoirs and emphasizes the need for preparedness against the potential spill-over of these viruses to local residents living near bat caves. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-018-0017-2) contains supplementary material, which is available to authorized users.",,"['Luo, Yun', 'Li, Bei', 'Jiang, Ren-Di', 'Hu, Bing-Jie', 'Luo, Dong-Sheng', 'Zhu, Guang-Jian', 'Hu, Ben', 'Liu, Hai-Zhou', 'Zhang, Yun-Zhi', 'Yang, Xing-Lou', 'Shi, Zheng-Li']",,,,
,PMC,"Serological Evidence of Bat SARS-Related Coronavirus Infection in Humans, China",http://dx.doi.org/10.1007/s12250-018-0012-7,PMC6178078,,,,,"['Wang, Ning', 'Li, Shi-Yue', 'Yang, Xing-Lou', 'Huang, Hui-Min', 'Zhang, Yu-Ji', 'Guo, Hua', 'Luo, Chu-Ming', 'Miller, Maureen', 'Zhu, Guangjian', 'Chmura, Aleksei A.', 'Hagan, Emily', 'Zhou, Ji-Hua', 'Zhang, Yun-Zhi', 'Wang, Lin-Fa', 'Daszak, Peter', 'Shi, Zheng-Li']",,,,
,PMC,"Delays in Global Disease Outbreak Responses: Lessons from H1N1, Ebola, and Zika",http://dx.doi.org/10.2105/AJPH.2017.304245,PMC5803810,,,"In global disease outbreaks, there are significant time delays between the source of an outbreak and collective action. Some delay is necessary, but recent delays have been extended by insufficient surveillance capacity and time-consuming efforts to mobilize action. Three public health emergencies of international concern (PHEICs)—H1N1, Ebola, and Zika—allow us to identify and compare sources of delays and consider seven hypotheses about what influences the length of delays. These hypotheses can then motivate further research that empirically tests them. The three PHEICs suggest that deferred global mobilization is a greater source of delay than is poor surveillance capacity. These case study outbreaks support hypotheses that we see quicker responses for novel diseases when outbreaks do not coincide with holidays and when US citizens are infected. They do not support hypotheses that we see quicker responses for more severe outbreaks or those that threaten larger numbers of people. Better understanding the reason for delays can help target policy interventions and identify the kind of global institutional changes needed to reduce the spread and severity of future PHEICs.",,"['Hoffman, Steven J.', 'Silverberg, Sarah L.']",,,,
,PMC,Rhesus θ-Defensin-1 Attenuates Endotoxin-induced Acute Lung Injury by Inhibiting Proinflammatory Cytokines and Neutrophil Recruitment,http://dx.doi.org/10.1165/rcmb.2016-0428OC,PMC5854954,,,"Acute lung injury (ALI) is a clinical syndrome characterized by acute respiratory failure and is associated with substantial morbidity and mortality. Rhesus θ-defensin (RTD)-1 is an antimicrobial peptide with immunomodulatory activity. As airway inflammation and neutrophil recruitment and activation are hallmarks of ALI, we evaluated the therapeutic efficacy of RTD-1 in preclinical models of the disease. We investigated the effect of RTD-1 on neutrophil chemotaxis and macrophage-driven pulmonary inflammation with human peripheral neutrophils and LPS-stimulated murine alveolar macrophage (denoted MH-S) cells. Treatment and prophylactic single escalating doses were administered subcutaneously in a well-established murine model of direct endotoxin-induced ALI. We assessed lung injury by histopathology, pulmonary edema, inflammatory cell recruitment, and inflammatory cytokines/chemokines in the BAL fluid. In vitro studies demonstrated that RTD-1 suppressed CXCL8-induced neutrophil chemotaxis, TNF-mediated neutrophil–endothelial cell adhesion, and proinflammatory cytokine release in activated murine alveolar immortalized macrophages (MH-S) cells. Treatment with RTD-1 significantly inhibited in vivo LPS-induced ALI by reducing pulmonary edema and histopathological changes. Treatment was associated with dose- and time-dependent inhibition of proinflammatory cytokines (TNF, IL-1β, and IL-6), peroxidase activity, and neutrophil recruitment into the airways. Antiinflammatory effects were demonstrated in animals receiving RTD-1 up to 12 hours after LPS challenge. Notably, subcutaneously administered RTD-1 demonstrates good peptide stability as demonstrated by the long in vivo half-life. Taken together, these studies demonstrate that RTD-1 is efficacious in an experimental model of ALI through inhibition of neutrophil chemotaxis and adhesion, and the attenuation of proinflammatory cytokines and gene expression from alveolar macrophages.",,"['Jayne, Jordanna G.', 'Bensman, Timothy J.', 'Schaal, Justin B.', 'Park, A. Young J.', 'Kimura, Elza', 'Tran, Dat', 'Selsted, Michael E.', 'Beringer, Paul M.']",,,,
,PMC,Cadherin-related Family Member 3 Genetics and Rhinovirus C Respiratory Illnesses,http://dx.doi.org/10.1164/rccm.201705-1021OC,PMC6005238,,,"Rationale: Experimental evidence suggests that CDHR3 (cadherin-related family member 3) is a receptor for rhinovirus (RV)-C, and a missense variant in this gene (rs6967330) is associated with childhood asthma with severe exacerbations. Objectives: To determine whether rs6967330 influences RV-C infections and illnesses in early childhood. Methods: We studied associations between rs6967330 and respiratory infections and illnesses in the COPSAC(2010) (Copenhagen Prospective Studies on Asthma in Childhood 2010) and COAST (Childhood Origins of Asthma Birth Cohort Study) birth cohorts, where respiratory infections were monitored prospectively for the first 3 years of life. Nasal samples were collected during acute infections in both cohorts and during asymptomatic periods in COAST and analyzed for RV-A, RV-B, and RV-C, and other common respiratory viruses. Measurements and Main Results: The CDHR3 asthma risk allele (rs6967330-A) was associated with increased risk of respiratory tract illnesses (incidence risk ratio [IRR] = 1.14 [95% confidence interval, 1.05–1.23]; P = 0.003). In particular, this variant was associated with risk of respiratory episodes with detection of RV-C in COPSAC(2010) (IRR = 1.89 [1.14–3.05]; P = 0.01) and in COAST (IRR = 1.37 [1.02–1.82]; P = 0.03) children, and in a combined meta-analysis (IRR = 1.51 [1.13–2.02]; P = 0.006). In contrast, the variant was not associated with illnesses related to other viruses (IRR = 1.07 [0.92–1.25]; P = 0.37). Consistent with these observations, the CDHR3 variant was associated with increased detection of RV-C, but not of other viruses during scheduled visits at specific ages. Conclusions: The CDHR3 asthma risk allele is associated specifically with RV-C illnesses in two birth cohorts. This clinical evidence supports earlier molecular evidence indicating that CDHR3 functions as an RV-C receptor, and raises the possibility of preventing RV-C infections by targeting CDHR3.",,"['Bønnelykke, Klaus', 'Coleman, Amaziah T.', 'Evans, Michael D.', 'Thorsen, Jonathan', 'Waage, Johannes', 'Vissing, Nadja H.', 'Carlsson, Christian J.', 'Stokholm, Jakob', 'Chawes, Bo L.', 'Jessen, Leon E.', 'Fischer, Thea K.', 'Bochkov, Yury A.', 'Ober, Carole', 'Lemanske, Robert F.', 'Jackson, Daniel J.', 'Gern, James E.', 'Bisgaard, Hans']",,,,
,PMC,Evaluation of real-time reverse-transcription loop-mediated isothermal amplification assay for clinical diagnosis of West Nile virus in patients,http://dx.doi.org/10.4103/0971-5916.234607,PMC6022379,29923519,CC BY-NC-SA,"BACKGROUND & OBJECTIVES: West Nile virus (WNV) is a mosquito-borne flavivirus. The disease can be diagnosed by isolation followed by fluorescent antibody tests, enzyme-linked immunosorbent assay and polymerase chain reaction (PCR) assay. These diagnostic methods are laborious and time-consuming. The present study was aimed to evaluate the real-time reverse-transcription loop-mediated isothermal amplification (RT-LAMP) method for rapid, early and accurate diagnosis of WNV. METHODS: A one-step single tube accelerated quantitative RT-LAMP assay was evaluated by targeting the Env gene of WNV. The gene amplification was accomplished by incubating the reaction mixture at 63°C for 60 min in both real time turbidimeter as well as routine laboratory water bath/dry heating bath. To rule out contamination issues, proper negative controls, including no template, no primer; and no enzyme, were always kept alongside each run. The RT-LAMP assay was evaluated on 105 clinical samples from individuals having ocular infection. RESULTS: Of the 105 samples tested, 27 were positive for WNV by RT-LAMP assay. The comparative evaluation with conventional RT-PCR revealed 100 per cent accordance with sensitivity and specificity of 100 and 95 per cent, respectively. The specificity of this assay was confirmed with serum samples obtained from patients with dengue and chikungunya. INTERPRETATION & CONCLUSIONS: The RT-LAMP test seemed to be a sensitive and specific method for rapid detection of WNV infection and would be useful for rapid screening of a large number of clinical samples in endemic areas during outbreaks.",2018 Mar,"['Kumar, Jyoti S.', 'Saxena, Divyasha', 'Parida, Manmohan', 'Rathinam, Sivakumar']",Indian J Med Res,,,
,PMC,Bias in Rating of Rodent Distress during Anesthesia Induction for Anesthesia Compared with Euthanasia,,PMC5868381,,,"Selection of an appropriate method of euthanasia involves balancing the wellbeing of the animal during the procedure with the intended use of the animal after death and the physical and psychologic safety of the observer or operator. The recommended practices for anesthesia as compared with euthanasia are very disparate, despite the fact that all chemical methods of euthanasia are anesthetic overdoses. To explain this disparity, this study sought to determine whether perception bias is inherent in the discussion of euthanasia compared with anesthesia. In this study, participants viewed videorecordings of the anesthesia of either 4 rats or 4 mice, from induction to loss of consciousness. Half of the participants were told that they were observing anesthesia; the other half understood that they were observing euthanasia. Participants were asked to rate the distress of the animals by scoring escape behaviors, fear behaviors, respiratory distress, and other distress markers. For mice, the participants generally rated the distress as high when they were told that the mouse was being euthanized, as compared with the participants who were told that the mouse was being anesthetized. For rats, the effect was not as strong, and the distress was generally rated higher when participants were told they were watching anesthesia. Because the interpretation of distress showed bias in both species—even though the bias differed regarding the procedure that interpreted as distressing—this study demonstrates that laboratory animal professionals must consider the influence of potential perception bias when developing policies for euthanasia and anesthesia.",,"['Baker, Brittany A', 'Hickman, Debra L']",,,,
,PMC,Nipah virus epidemic in southern India and emphasizing “One Health” approach to ensure global health security,http://dx.doi.org/10.4103/jfmpc.jfmpc_137_18,PMC6060941,30090764,CC BY-NC-SA,"Nipah virus (NiV) encephalitis first reported in “Sungai Nipah” in Malaysia in 1999 has emerged as a global public health threat in the Southeast Asia region. From 1998 to 2018, more than 630 cases of NiV human infections were reported. NiV is transmitted by zoonotic (from bats to humans, or from bats to pigs, and then to humans) as well as human-to-human routes. Deforestation and urbanization of some areas have contributed to greater overlap between human and bat habitats resulting in NiV outbreaks. Common symptoms of NiV infection in humans are similar to that of influenza such as fever and muscle pain and in some cases, the inflammation of the brain occurs leading to encephalitis. The recent epidemic in May 2018 in Kerala for the first time has killed over 17 people in 7 days with high case fatality and highlighted the importance of One Health approach. The diagnosis is often not suspected at the time of presentation and creates challenges in outbreak detection, timely control measures, and outbreak response activities. Currently, there are no drugs or vaccines specific for NiV infection although this is a priority disease on the World Health Organization's agenda. Antivirals (Ribavirin, HR2-based fusion inhibitor), biologicals (convalescent plasma, monoclonal antibodies), immunomodulators, and intensive supportive care are the mainstay to treat severe respiratory and neurologic complications. There is a great need for strengthening animal health surveillance system, using a One Health approach, to detect new cases and provide early warning for veterinary and human public health authorities.",2018 Mar-Apr,"['Chattu, Vijay K.', 'Kumar, Raman', 'Kumary, Soosanna', 'Kajal, Fnu', 'David, Joseph K.']",J Family Med Prim Care,,,
,PMC,Assessment of a respiratory face mask for capturing air pollutants and pathogens including human influenza and rhinoviruses,http://dx.doi.org/10.21037/jtd.2018.03.103,PMC5906272,,,"BACKGROUND: Prevention of infection with airborne pathogens and exposure to airborne particulates and aerosols (environmental pollutants and allergens) can be facilitated through use of disposable face masks. The effectiveness of such masks for excluding pathogens and pollutants is dependent on the intrinsic ability of the masks to resist penetration by airborne contaminants. This study evaluated the relative contributions of a mask, valve, and Micro Ventilator on aerosol filtration efficiency of a new N95 respiratory face mask. METHODS: The test mask was challenged, using standardized methods, with influenza A and rhinovirus type 14, bacteriophage ΦΧ174, Staphylococcus aureus (S. aureus), and model pollutants. The statistical significance of results obtained for different challenge microbial agents and for different mask configurations (masks with operational or nonoperational ventilation fans and masks with sealed Smart Valves) was assessed. RESULTS: The results demonstrate >99.7% efficiency of each test mask configuration for exclusion of influenza A virus, rhinovirus 14, and S. aureus and >99.3% efficiency for paraffin oil and sodium chloride (surrogates for PM(2.5)). Statistically significant differences in effectiveness of the different mask configurations were not identified. The efficiencies of the masks for excluding smaller-size (i.e., rhinovirus and bacteriophage ΦΧ174) vs. larger-size microbial agents (influenza virus, S. aureus) were not significantly different. CONCLUSIONS: The masks, with or without features intended for enhancing comfort, provide protection against both small- and large-size pathogens. Importantly, the mask appears to be highly efficient for filtration of pathogens, including influenza and rhinoviruses, as well as the fine particulates (PM(2.5)) present in aerosols that represent a greater challenge for many types of dental and surgical masks. This renders this individual-use N95 respiratory mask an improvement over the former types of masks for protection against a variety of environmental contaminants including PM(2.5) and pathogens such as influenza and rhinoviruses.",,"['Zhou, S. Steve', 'Lukula, Salimatu', 'Chiossone, Cory', 'Nims, Raymond W.', 'Suchmann, Donna B.', 'Ijaz, M. Khalid']",,,,
,PMC,Measles Vaccine,http://dx.doi.org/10.1089/vim.2017.0143,PMC5863094,,,"Measles remains an important cause of child morbidity and mortality worldwide despite the availability of a safe and efficacious vaccine. The current measles virus (MeV) vaccine was developed empirically by attenuation of wild-type (WT) MeV by in vitro passage in human and chicken cells and licensed in 1963. Additional passages led to further attenuation and the successful vaccine strains in widespread use today. Attenuation is associated with decreased replication in lymphoid tissue, but the molecular basis for this restriction has not been identified. The immune response is age dependent, inhibited by maternal antibody (Ab) and involves induction of both Ab and T cell responses that resemble the responses to WT MeV infection, but are lower in magnitude. Protective immunity is correlated with levels of neutralizing Ab, but the actual immunologic determinants of protection are not known. Because measles is highly transmissible, control requires high levels of population immunity. Delivery of the two doses of vaccine needed to achieve >90% immunity is accomplished by routine immunization of infants at 9–15 months of age followed by a second dose delivered before school entry or by periodic mass vaccination campaigns. Because delivery by injection creates hurdles to sustained high coverage, there are efforts to deliver MeV vaccine by inhalation. In addition, the safety record for the vaccine combined with advances in reverse genetics for negative strand viruses has expanded proposed uses for recombinant versions of measles vaccine as vectors for immunization against other infections and as oncolytic agents for a variety of tumors.",,"Griffin, Diane E.",,,,
,PMC,Integrative Physiological Aspects of Brain RAS in Hypertension,http://dx.doi.org/10.1007/s11906-018-0810-1,PMC6324839,,,"PURPOSE OF REVIEW: The renin-angiotensin system (RAS) plays an important role in modulating cardiovascular function and fluid homeostasis. While the systemic actions of the RAS are widely accepted, the role of the RAS in the brain, its regulation of cardiovascular function, and sympathetic outflow remain controversial. In this report, we discuss the current understanding of central RAS on blood pressure (BP) regulation, in light of recent literature and new experimental techniques. RECENT FINDINGS: Studies using neuronal or glial-specifc mouse models have allowed for greater understanding into the site-specific expression and role centrally expressed RAS proteins have on BP regulation. While all components of the RAS have been identified in cardiovascular regulatory regions of the brain, their actions may be site specific. In a number of animal models of hypertension, reduction in Ang II-mediated signaling, or upregulation of the central ACE2/Ang 1–7 pathway, has been shown to reduce BP, via a reduction in sympathetic signaling and increase parasympathetic tone, respectively. Emerging evidence also suggests that, in part, the female protective phenotype against hypertension may be due to inceased ACE2 activity within cardiovascular regulatory regions of the brain, potentially mediated by estrogen. SUMMARY: Increasing evidence suggests the importance of a central renin-angiotensin pathway, although its localization and the mechanisms involved in its expression and regulation still need to be clarified and more precisely defined. All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).",,"['de Morais, Sharon D. B.', 'Shanks, Julia', 'Zucker, Irving H.']",,,,
,PMC,Activities of Thrombin and Factor Xa Are Essential for Replication of Hepatitis E Virus and Are Possibly Implicated in ORF1 Polyprotein Processing,http://dx.doi.org/10.1128/JVI.01853-17,PMC5827406,,,"Hepatitis E virus (HEV) is a clinically important positive-sense RNA virus. The ORF1 of HEV encodes a nonstructural polyprotein of 1,693 amino acids. It is not clear whether the ORF1 polyprotein (pORF1) is processed into distinct enzymatic domains. Many researchers have attempted to understand the mechanisms of pORF1 processing. However, these studies gave various results and could never convincingly establish the mechanism of pORF1 processing. In this study, we demonstrated the possible role of thrombin and factor Xa in pORF1 processing. We observed that the HEV pORF1 polyprotein bears conserved cleavage sites of thrombin and factor Xa. Using a reverse genetics approach, we demonstrated that an HEV replicon having mutations in the cleavage sites of either thrombin or factor Xa could not replicate efficiently in cell culture. Further, we demonstrated in vitro processing when we incubated recombinant pORF1 fragments with thrombin, and we observed the processing of pORF1 polyprotein. The treatment of a liver cell line with a serine protease inhibitor as well as small interfering RNA (siRNA) knockdown of thrombin and factor Xa resulted in significant reduction in the replication of HEV. Thrombin and factor Xa have been well studied for their roles in blood clotting. Both of these proteins are believed to be present in the active form in the blood plasma. Interestingly, in this report, we demonstrated the presence of biologically active thrombin and factor Xa in a liver cell line. The results suggest that factor Xa and thrombin are essential for the replication of HEV and may be involved in pORF1 polyprotein processing of HEV. IMPORTANCE Hepatitis E virus (HEV) causes a liver disorder called hepatitis in humans, which is mostly an acute and self-limiting infection in adults. A high mortality rate of about 30% is observed in HEV-infected pregnant women in developing countries. There is no convincing opinion about HEV ORF1 polyprotein processing owing to the variability of study results obtained so far. HEV pORF1 has cleavage sites for two host cellular serine proteases, thrombin and factor Xa, that are conserved among HEV genotypes. For the first time, this study demonstrated that thrombin and factor Xa cleavage sites on HEV pORF1 are obligatory for HEV replication. Intracellular biochemical activities of the said serine proteases are also essential for efficient HEV replication in cell culture and must be involved in pORF1 processing. This study sheds light on the presence and roles of clotting factors with respect to virus replication in the cells.",,"['Kanade, Gayatri D.', 'Pingale, Kunal D.', 'Karpe, Yogesh A.']",,,,
,PMC,Identification of Residues Controlling Restriction versus Enhancing Activities of IFITM Proteins on Entry of Human Coronaviruses,http://dx.doi.org/10.1128/JVI.01535-17,PMC5827390,,,"Interferon-induced transmembrane proteins (IFITMs) are restriction factors that inhibit the infectious entry of many enveloped RNA viruses. However, we demonstrated previously that human IFITM2 and IFITM3 are essential host factors facilitating the entry of human coronavirus (HCoV) OC43. In a continuing effort to decipher the molecular mechanism underlying IFITM differential modulation of HCoV entry, we investigated the roles of structural motifs important for IFITM protein posttranslational modifications, intracellular trafficking, and oligomerization in modulating the entry of five HCoVs. We found that three distinct mutations in IFITM1 or IFITM3 converted the host restriction factors to enhance entry driven by the spike proteins of severe acute respiratory syndrome coronavirus (SARS-CoV) and/or Middle East respiratory syndrome coronavirus (MERS-CoV). First, replacement of IFITM3 tyrosine 20 with either alanine or aspartic acid to mimic unphosphorylated or phosphorylated IFITM3 reduced its activity to inhibit the entry of HCoV-NL63 and -229E but enhanced the entry of SARS-CoV and MERS-CoV. Second, replacement of IFITM3 tyrosine 99 with either alanine or aspartic acid reduced its activity to inhibit the entry of HCoV-NL63 and SARS-CoV but promoted the entry of MERS-CoV. Third, deletion of the carboxyl-terminal 12 amino acid residues from IFITM1 enhanced the entry of MERS-CoV and HCoV-OC43. These findings suggest that these residues and structural motifs of IFITM proteins are key determinants for modulating the entry of HCoVs, most likely through interaction with viral and/or host cellular components at the site of viral entry to modulate the fusion of viral envelope and cellular membranes. IMPORTANCE The differential effects of IFITM proteins on the entry of HCoVs that utilize divergent entry pathways and membrane fusion mechanisms even when using the same receptor make the HCoVs a valuable system for comparative investigation of the molecular mechanisms underlying IFITM restriction or promotion of virus entry into host cells. Identification of three distinct mutations that converted IFITM1 or IFITM3 from inhibitors to enhancers of MERS-CoV or SARS-CoV spike protein-mediated entry revealed key structural motifs or residues determining the biological activities of IFITM proteins. These findings have thus paved the way for further identification of viral and host factors that interact with those structural motifs of IFITM proteins to differentially modulate the infectious entry of HCoVs.",,"['Zhao, Xuesen', 'Sehgal, Mohit', 'Hou, Zhifei', 'Cheng, Junjun', 'Shu, Sainan', 'Wu, Shuo', 'Guo, Fang', 'Le Marchand, Sylvain J.', 'Lin, Hanxin', 'Chang, Jinhong', 'Guo, Ju-Tao']",,,,
,PMC,Paramyxovirus V Proteins Interact with the RIG-I/TRIM25 Regulatory Complex and Inhibit RIG-I Signaling,http://dx.doi.org/10.1128/JVI.01960-17,PMC5827389,,,"Paramyxovirus V proteins are known antagonists of the RIG-I-like receptor (RLR)-mediated interferon induction pathway, interacting with and inhibiting the RLR MDA5. We report interactions between the Nipah virus V protein and both RIG-I regulatory protein TRIM25 and RIG-I. We also observed interactions between these host proteins and the V proteins of measles virus, Sendai virus, and parainfluenza virus. These interactions are mediated by the conserved C-terminal domain of the V protein, which binds to the tandem caspase activation and recruitment domains (CARDs) of RIG-I (the region of TRIM25 ubiquitination) and to the SPRY domain of TRIM25, which mediates TRIM25 interaction with the RIG-I CARDs. Furthermore, we show that V interaction with TRIM25 and RIG-I prevents TRIM25-mediated ubiquitination of RIG-I and disrupts downstream RIG-I signaling to the mitochondrial antiviral signaling protein. This is a novel mechanism for innate immune inhibition by paramyxovirus V proteins, distinct from other known V protein functions such as MDA5 and STAT1 antagonism. IMPORTANCE The host RIG-I signaling pathway is a key early obstacle to paramyxovirus infection, as it results in rapid induction of an antiviral response. This study shows that paramyxovirus V proteins interact with and inhibit the activation of RIG-I, thereby interrupting the antiviral signaling pathway and facilitating virus replication.",,"['Sánchez-Aparicio, Maria T.', 'Feinman, Leighland J.', 'García-Sastre, Adolfo', 'Shaw, Megan L.']",,,,
,PMC,Recombinant Chimpanzee Adenovirus Vaccine AdC7-M/E Protects against Zika Virus Infection and Testis Damage,http://dx.doi.org/10.1128/JVI.01722-17,PMC5827382,,,"The recent outbreak of Zika virus (ZIKV) has emerged as a global health concern. ZIKV can persist in human semen and be transmitted by sexual contact, as well as by mosquitoes, as seen for classical arboviruses. We along with others have previously demonstrated that ZIKV infection leads to testis damage and infertility in mouse models. So far, no prophylactics or therapeutics are available; therefore, vaccine development is urgently demanded. Recombinant chimpanzee adenovirus has been explored as the preferred vaccine vector for many pathogens due to the low preexisting immunity against the vector among the human population. Here, we developed a ZIKV vaccine based on recombinant chimpanzee adenovirus type 7 (AdC7) expressing ZIKV M/E glycoproteins. A single vaccination of AdC7-M/E was sufficient to elicit potent neutralizing antibodies and protective immunity against ZIKV in both immunocompetent and immunodeficient mice. Moreover, vaccinated mice rapidly developed neutralizing antibody with high titers within 1 week postvaccination, and the elicited antiserum could cross-neutralize heterologous ZIKV strains. Additionally, ZIKV M- and E-specific T cell responses were robustly induced by AdC7-M/E. Moreover, one-dose inoculation of AdC7-M/E conferred mouse sterilizing immunity to eliminate viremia and viral burden in tissues against ZIKV challenge. Further investigations showed that vaccination with AdC7-M/E completely protected against ZIKV-induced testicular damage. These data demonstrate that AdC7-M/E is highly effective and represents a promising vaccine candidate for ZIKV control. IMPORTANCE Zika virus (ZIKV) is a pathogenic flavivirus that causes severe clinical consequences, including congenital malformations in fetuses and Guillain-Barré syndrome in adults. Vaccine development is a high priority for ZIKV control. In this study, to avoid preexisting anti-vector immunity in humans, a rare serotype chimpanzee adenovirus (AdC7) expressing the ZIKV M/E glycoproteins was used for ZIKV vaccine development. Impressively, AdC7-M/E exhibited exceptional performance as a ZIKV vaccine, as follows: (i) protective efficacy by a single vaccination, (ii) rapid development of a robust humoral response, (iii) durable immune responses, (iv) robust T cell responses, and (v) sterilizing immunity achieved by a single vaccination. These advantages of AdC7-M/E strongly support its potential application as a promising ZIKV vaccine in the clinic.",,"['Xu, Kun', 'Song, Yufeng', 'Dai, Lianpan', 'Zhang, Yongli', 'Lu, Xuancheng', 'Xie, Yijia', 'Zhang, Hangjie', 'Cheng, Tao', 'Wang, Qihui', 'Huang, Qingrui', 'Bi, Yuhai', 'Liu, William J.', 'Liu, Wenjun', 'Li, Xiangdong', 'Qin, Chuan', 'Shi, Yi', 'Yan, Jinghua', 'Zhou, Dongming', 'Gao, George F.']",,,,
,PMC,Interleukin-10 Modulation of Virus Clearance and Disease in Mice with Alphaviral Encephalomyelitis,http://dx.doi.org/10.1128/JVI.01517-17,PMC5827374,,,"Alphaviruses are an important cause of mosquito-borne outbreaks of arthritis, rash, and encephalomyelitis. Previous studies in mice with a virulent strain (neuroadapted SINV [NSV]) of the alphavirus Sindbis virus (SINV) identified a role for Th17 cells and regulation by interleukin-10 (IL-10) in the pathogenesis of fatal encephalomyelitis (K. A. Kulcsar, V. K. Baxter, I. P. Greene, and D. E. Griffin, Proc Natl Acad Sci U S A 111:16053–16058, 2014, https://doi.org/10.1073/pnas.1418966111). To determine the role of virus virulence in generation of immune responses, we analyzed the modulatory effects of IL-10 on disease severity, virus clearance, and the CD4(+) T cell response to infection with a recombinant strain of SINV of intermediate virulence (TE12). The absence of IL-10 during TE12 infection led to longer morbidity, more weight loss, higher mortality, and slower viral clearance than in wild-type mice. More severe disease and impaired virus clearance in IL-10(−/−) mice were associated with more Th1 cells, fewer Th2 cells, innate lymphoid type 2 cells, regulatory cells, and B cells, and delayed production of antiviral antibody in the central nervous system (CNS) without an effect on Th17 cells. Therefore, IL-10 deficiency led to more severe disease in TE12-infected mice by increasing Th1 cells and by hampering development of the local B cell responses necessary for rapid production of antiviral antibody and virus clearance from the CNS. In addition, the shift from Th17 to Th1 responses with decreased virus virulence indicates that the effects of IL-10 deficiency on immunopathologic responses in the CNS during alphavirus infection are influenced by virus strain. IMPORTANCE Alphaviruses cause mosquito-borne outbreaks of encephalomyelitis, but determinants of outcome are incompletely understood. We analyzed the effects of the anti-inflammatory cytokine IL-10 on disease severity and virus clearance after infection with an alphavirus strain of intermediate virulence. The absence of IL-10 led to longer illness, more weight loss, more death, and slower viral clearance than in mice that produced IL-10. IL-10 influenced development of disease-causing T cells and entry into the brain of B cells producing antiviral antibody. The Th1 pathogenic cell subtype that developed in IL-10-deficient mice infected with a less virulent virus was distinct from the Th17 subtype that developed in response to a more virulent virus, indicating a role for virus strain in determining the immune response. Slow production of antibody in the nervous system led to delayed virus clearance. Therefore, both the virus strain and the host response to infection are important determinants of outcome.",,"['Martin, Nina M.', 'Griffin, Diane E.']",,,,
,PMC,Forecasting the spatial transmission of influenza in the United States,http://dx.doi.org/10.1073/pnas.1708856115,PMC5856508,,,"Recurrent outbreaks of seasonal and pandemic influenza create a need for forecasts of the geographic spread of this pathogen. Although it is well established that the spatial progression of infection is largely attributable to human mobility, difficulty obtaining real-time information on human movement has limited its incorporation into existing infectious disease forecasting techniques. In this study, we develop and validate an ensemble forecast system for predicting the spatiotemporal spread of influenza that uses readily accessible human mobility data and a metapopulation model. In retrospective state-level forecasts for 35 US states, the system accurately predicts local influenza outbreak onset,—i.e., spatial spread, defined as the week that local incidence increases above a baseline threshold—up to 6 wk in advance of this event. In addition, the metapopulation prediction system forecasts influenza outbreak onset, peak timing, and peak intensity more accurately than isolated location-specific forecasts. The proposed framework could be applied to emergent respiratory viruses and, with appropriate modifications, other infectious diseases.",,"['Pei, Sen', 'Kandula, Sasikiran', 'Yang, Wan', 'Shaman, Jeffrey']",,,,
,PMC,Engineering a stable CHO cell line for the expression of a MERS-coronavirus vaccine antigen,http://dx.doi.org/10.1016/j.vaccine.2018.02.065,PMC5860679,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 2,040 patients and caused 712 deaths since its first appearance in 2012, yet neither pathogen-specific therapeutics nor approved vaccines are available. To address this need, we are developing a subunit recombinant protein vaccine comprising residues 377 to 588 of the MERS-CoV spike protein receptor-binding domain (RBD), which, when formulated with the AddaVax adjuvant, it induces a significant neutralizing antibody response and protection against MERS-CoV challenge in vaccinated animals. To prepare for the manufacture and first-in-human testing of the vaccine, we have developed a process to stably produce the recombinant MERS S377–588 protein in Chinese hamster ovary (CHO) cells. To accomplish this, we transfected an adherent dihydrofolate reductase-deficient CHO cell line (adCHO) with a plasmid encoding S377–588 fused with the human IgG Fc fragment (S377-588-Fc). We then demonstrated the interleukin-2 signal peptide-directed secretion of the recombinant protein into extracellular milieu. Using a gradually increasing methotrexate (MTX) concentration to 5 μM, we increased protein yield by a factor of 40. The adCHO-expressed S377-588-Fc recombinant protein demonstrated functionality and binding specificity identical to those of the protein from transiently transfected HEK293T cells. In addition, hCD26/dipeptidyl peptidase-4 (DPP4) transgenic mice vaccinated with AddaVax-adjuvanted S377-588-Fc could produce neutralizing antibodies against MERS-CoV and survived for at least 21 days after challenge with live MERS-CoV with no evidence of immunological toxicity or eosinophilic immune enhancement. To prepare for large scale-manufacture of the vaccine antigen, we have further developed a high-yield monoclonal suspension CHO cell line.",,"['Nyon, Mun Peak', 'Du, Lanying', 'Tseng, Chien-Te Kent', 'Seid, Christopher A.', 'Pollet, Jeroen', 'Naceanceno, Kevin S.', 'Agrawal, Anurodh', 'Algaissi, Abdullah', 'Peng, Bi-Hung', 'Tai, Wanbo', 'Jiang, Shibo', 'Bottazzi, Maria Elena', 'Strych, Ulrich', 'Hotez, Peter J.']",,,,
,PMC,Viral manipulation of host mRNA decay,http://dx.doi.org/10.2217/fvl-2017-0106,PMC5939598,,,"Viruses alter host–cell gene expression at many biochemical levels, such as transcription, translation, mRNA splicing and mRNA decay in order to create a cellular environment suitable for viral replication. In this review, we discuss mechanisms by which viruses manipulate host–gene expression at the level of mRNA decay in order to enable the virus to evade host antiviral responses to allow viral survival and replication. We discuss different cellular RNA decay pathways, including the deadenylation-dependent mRNA decay pathway, and various strategies that viruses exploit to manipulate these pathways in order to create a virus-friendly cellular environment.",,"['Guo, Liang', 'Vlasova-St Louis, Irina', 'Bohjanen, Paul R']",,,,
,PMC,TNFα and Radioresistant Stromal Cells Are Essential for Therapeutic Efficacy of Cyclic Dinucleotide STING Agonists in Nonimmunogenic Tumors,http://dx.doi.org/10.1158/2326-6066.CIR-17-0263,PMC6215542,,,"The cGAS-STING cytosolic DNA sensing pathway may play an integral role in the initiation of antitumor immune responses. Studies evaluating the immunogenicity of various cyclic dinucleotide (CDN) STING agonists administered by intratumoral (i.t.) injection showed potent induction of inflammation, tumor necrosis, and, in some cases, durable tumor-specific adaptive immunity. However, the specific immune mechanisms underlying these responses remain incompletely defined. The majority of these studies have focused on the effect of CDNs on immune cells but have not conclusively interrogated the role of stromal cells in the acute rejection of the CDN-injected tumor. Here, we revealed a mechanism of STING agonist-mediated tumor response that relied on both stromal and immune cells to achieve tumor regression and clearance. Using knockout and bone marrow chimeric mice, we showed that although bone marrow–derived TNFα was necessary for CDN-induced necrosis, STING signaling in radioresistant stromal cells was also essential for CDN-mediated tumor rejection. These results provide evidence for crosstalk between stromal and hematopoietic cells during CDN-mediated tumor collapse after i.t. administration. These mechanistic insights may prove critical in the clinical development of STING agonists.",,"['Francica, Brian J.', 'Ghasemzadeh, Ali', 'Desbien, Anthony L.', 'Theodros, Debebe', 'Sivick, Kelsey E.', 'Reiner, Gabrielle L.', 'Glickman, Laura Hix', 'Marciscano, Ariel E.', 'Sharabi, Andrew B.', 'Leong, Meredith L.', 'McWhirter, Sarah M.', 'Dubensky, Thomas W.', 'Pardoll, Drew M.', 'Drake, Charles G.']",,,,
,PMC,Cytokine Release Syndrome Grade as a Predictive Marker for Infections in Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia Treated With Chimeric Antigen Receptor T Cells,http://dx.doi.org/10.1093/cid/ciy152,PMC6070095,,,"BACKGROUND: Chimeric antigen receptor (CAR)–modified T cells that target the CD19 antigen present a novel promising therapy for the treatment of relapsed B-cell acute lymphoblastic leukemia (B-ALL). Although cytokine release syndrome (CRS) and neurotoxicity have emerged as predominant noninfectious complications of CD19 CAR T-cell therapy, infections associated with this treatment modality have not been well documented. METHODS: We analyzed infectious complications that followed CD19 CAR T-cell therapy in 53 adult patients with relapsed B-ALL enrolled in a phase I clinical trial at Memorial Sloan Kettering Cancer Center (NCT01044069). RESULTS: Overall, 22 patients (42%) experienced 26 infections (17 bacterial, 4 fungal, and 5 viral) within the first 30 days of CAR T-cell infusion. In 10 of 32 (31%) patients in whom complete remission was achieved, 15 infections developed between days 31 and 180; the majority of these late infections were due to respiratory viruses. In general, bacterial, fungal, and viral infections were detected at a median of 18, 23, and 48 days, respectively, after CAR T-cell infusion. CRS grade 3 or higher was independently associated with increased risk of subsequent infection (adjusted hazard ratio [HR], 2.67; P = .05) and in particular with bloodstream infection (adjusted HR, 19.97; P < .001). Three of 53 patients (6%) died of an infection-related cause. CONCLUSIONS: Infections in adult patients with relapsed B-ALL are common after CD19 CAR T-cell therapy. Understanding the infectious complications that are temporally coincident with CD19 CAR T-cell therapy is critical for developing effective prophylactic and other supportive care measures to improve clinical outcomes. CLINICAL TRIALS REGISTRATION: NCT01044069.",,"['Park, Jae H', 'Romero, F Andres', 'Taur, Ying', 'Sadelain, Michel', 'Brentjens, Renier J', 'Hohl, Tobias M', 'Seo, Susan K']",,,,
,PMC,Is regulation preventing the development of therapeutics that may prevent future coronavirus pandemics?,http://dx.doi.org/10.2217/fvl-2017-0143,PMC6289267,,,,,"['Sheahan, Timothy P', 'Baric, Ralph S']",,,,
,PMC,New insights about the regulation of Nidovirus subgenomic mRNA synthesis,http://dx.doi.org/10.1016/j.virol.2018.01.026,PMC5987246,,,"The members of the Order Nidovirales share a similar genome organization with the nonstructural proteins encoded at the 5ʹ end and the structural genes at the 3ʹ end and express the 3ʹ genes from a nested set of 3′ co-terminal subgenomic messenger RNAs (sg mRNAs). Some but not all of the Nidoviruses, the sg mRNAs also have a common 5ʹ leader sequence acquired by a discontinuous transcription mechanism regulated by multiple 3ʹ transcription regulatory sequences (TRS) and the 5ʹ leader TRS. Initial studies detected a single major body TRS for each 3ʹ genes with a few alternative functional TRSs reported. The recent application of advanced techniques, such as next generation sequencing and ribosomal profiling, in studies of arteriviruses and coronaviruses has revealed an expanded sg mRNA transcriptome and coding capacity.",,"['Di, Han', 'McIntyre, Ayisha A.', 'Brinton, Margo A.']",,,,
,PMC,Foot-and-mouth disease virus type O specific mutations determine RNA-dependent RNA polymerase fidelity and virus attenuation,http://dx.doi.org/10.1016/j.virol.2018.01.030,PMC5911202,,,"Previous studies have shown that the FMDV Asia1/YS/CHA/05 high-fidelity mutagen-resistant variants are attenuated (Zeng et al., 2014). Here, we introduced the same single or multiple-amino-acid substitutions responsible for increased 3D(pol) fidelity of type Asia1 FMDV into the type O FMDV O/YS/CHA/05 infectious clone. The rescued viruses O-DA and O-DAMM are lower replication fidelity mutants and showed an attenuated phenotype. These results demonstrated that the same amino acid substitution of 3D(pol) in different serotypes of FMDV strains had different effects on viral fidelity. In addition, nucleoside analogues were used to select high-fidelity mutagen-resistant type O FMDV variants. The rescued mutagen-resistant type O FMDV high-fidelity variants exhibited significantly attenuated fitness and a reduced virulence phenotype. These results have important implications for understanding the molecular mechanism of FMDV evolution and pathogenicity, especially in developing a safer modified live-attenuated vaccine against FMDV.",,"['Li, Chen', 'Wang, Haiwei', 'Yuan, Tiangang', 'Woodman, Andrew', 'Yang, Decheng', 'Zhou, Guohui', 'Cameron, Craig E.', 'Yu, Li']",,,,
,PMC,Genetic analysis of calf health in Charolais beef cattle,http://dx.doi.org/10.1093/jas/sky043,PMC6140890,,,"The objective of this study was to investigate the factors that influence calf health and survival in Charolais cattle. Data from 2,740 calves, originating from 16 French farms and observed from birth until 30 d of age, were analyzed using models that took account of direct genetic, maternal genetic, and common environmental effects. Both direct and maternal genetic parameters were estimated for birth weight (BW), calving ease (CE), neonatal vitality (NV), survival at 30 d (Surv), and umbilical infection and diarrhea at different ages (0 to 5 d: Umb1 and Diar1; 6 to 20 d: Umb2 and Diar2; and 21 to 30 d: Umb3 and Diar3). The heritability values for direct and maternal genetic effects were, 0.026 (SE = 0.027) and 0.096 (SE = 0.042) for Surv, 0.280 (SE = 0.063) and 0.063 (SE = 0.038) for BW, 0.129 (SE = 0.041) and 0 for CE, 0.073 (SE = 0.035) and 0 for NV, 0.071 (SE = 0.038) and 0.017 (SE = 0.026) for Umb1, 0 and 0.082 (SE = 0.029) for Umb2, 0 and 0.044 (SE = 0.030) for Diar1, 0.016 (SE = 0.022) and 0.012 (SE = 0.026) for Diar2, and 0.016 (SE = 0.028) and 0 for Diar3, respectively. Significant genetic variability in beef cattle was thus revealed for five calf health traits: NV, Surv, Diar1, Umb1, and Umb2. In addition, for three traits (Surv, Diar1, and Umb2), maternal genetic effects clearly contributed more to health performance than direct genetic effects. Estimates of genetic correlation between traits varied markedly (from 0 to 1 in absolute values) depending on the traits in question, the age for a given trait, and the type (direct or maternal) of the genetic effects considered. These results suggest that not all health traits in Charolais cattle can be improved simultaneously, and breeders will therefore have to prioritize certain traits of interest in their breeding objectives. Overall, our results demonstrate the potential utility of collecting and integrating data on calf diseases, NV and survival in future beef cattle breeding programs. To ensure appropriate biological and genetic evaluations of calf health performance, it is important to accurately describe the phenotypes for diarrhea and umbilical infections (in terms of age ranges) and account for maternal genetic and common environmental effects that explain calf health performance traits. Further investigation and improved data collection are now necessary to maximize the efficiency of breeding schemes designed to simultaneously improve production and health traits.",,"['Vinet, A', 'Leclerc, H', 'Marquis, F', 'Phocas, F']",,,,
,PMC,"Diarrhea caused by rotavirus A, B, and C in suckling piglets from southern Brazil: molecular detection and histologic and immunohistochemical characterization",http://dx.doi.org/10.1177/1040638718756050,PMC6505807,,,"Rotavirus (RV) is an important viral pathogen causing diarrhea in piglets and other mammals worldwide. We describe 34 cases from 4 diarrheal outbreaks caused by RV in unvaccinated farrowing units in southern Brazil from 2011 to 2013. We performed autopsy, histologic examinations, bacterial culture, RV immunohistochemistry (IHC), and enteric virus detection through molecular assays for rotavirus A, B, and C, transmissible gastroenteritis virus, porcine epidemic diarrhea virus, sapovirus, norovirus, and kobuvirus. Histologically, villus atrophy (29 of 34) and epithelial vacuolation (27 of 34) occurred in all 4 outbreaks. Cell debris in the lamina propria occurred in 20 cases, mostly from outbreaks A (8 of 11), C (4 of 6), and D (7 of 11). IHC was positive for RV in 21 of 34 samples. RT-PCR was positive for RV in 20 of 30 samples; RV-C was the most frequently detected RV (n = 17). Kobuvirus was detected in 11 samples, and, in 3 of them, there was single detection of this enteric virus.",,"['Almeida, Paula R.', 'Lorenzetti, Elis', 'Cruz, Raquel S.', 'Watanabe, Tatiane T.', 'Zlotowski, Priscila', 'Alfieri, Amauri A.', 'Driemeier, David']",,,,
,PMC,Genomic Characterization of a Novel Hepatovirus from Great Roundleaf Bats in China,http://dx.doi.org/10.1007/s12250-018-0013-6,PMC6178082,,,,,"['Li, Wen', 'Wang, Bo', 'Li, Bei', 'Zhang, Wei', 'Zhu, Yan', 'Shi, Zheng-Li', 'Yang, Xing-Lou']",,,,
,PMC,Assessing Viral Transfer During Doffing of Ebola-Level Personal Protective Equipment in a Biocontainment Unit,http://dx.doi.org/10.1093/cid/cix956,PMC6927896,,,"BACKGROUND: Personal protective equipment (PPE) protects healthcare workers (HCWs) caring for patients with Ebola virus disease (EVD), and PPE doffing is a critical point for preventing viral self-contamination. We assessed contamination of skin, gloves, and scrubs after doffing Ebola-level PPE contaminated with surrogate viruses: bacteriophages MS2 and Φ6. METHODS: In a medical biocontainment unit, HCWs (n = 10) experienced in EVD care donned and doffed PPE following unit protocols that incorporate trained observer guidance and alcohol-based hand rub (ABHR). A mixture of Φ6 (enveloped), MS2 (nonenveloped), and fluorescent marker was applied to 4 PPE sites, approximating body fluid viral load (Φ6, 10(5); MS2, 10(6)). They performed a patient care task, then doffed. Inner gloves, face, hands, and scrubs were sampled for virus, as were environmental sites with visible fluorescent marker. RESULTS: Among 10 HCWs there was no Φ6 transfer to inner gloves, hands, or face; 1 participant had Φ6 on scrubs at low levels (1.4 × 10(2)). MS2 transfer (range, 10(1)–10(6)) was observed to scrubs (n = 2), hands (n = 1), and inner gloves (n = 7), where it was highest. Most (n = 8) had only 1 positive site. Environmental samples with visible fluorescent marker (n = 21) were negative. CONCLUSIONS: Among experienced HCWs, structured, observed doffing using ABHR protected against hand contamination with enveloped virus. Nonenveloped virus was infrequent on hands and scrubs but common on inner gloves, suggesting that inner gloves, but not necessarily ABHR, protect against hand contamination. Optimizing doffing protocols to protect against all types of viruses may require reinforcing careful handling of scrubs and good glove/hand hygiene with effective agents.",,"['Casanova, Lisa M', 'Erukunuakpor, Kimberly', 'Kraft, Colleen S', 'Mumma, Joel M', 'Durso, Francis T', 'Ferguson, Ashley N', 'Gipson, Christina L', 'Walsh, Victoria L', 'Zimring, Craig', 'DuBose, Jennifer', 'Jacob, Jesse T', None]",,,,
,PMC,"Initial Performance Evaluation of a Spotted Array Mobile Analysis Platform (MAP) for the Detection of Influenza A/B, RSV and MERS Coronavirus",http://dx.doi.org/10.1016/j.diagmicrobio.2018.02.011,PMC6013072,,,"Clinical samples were evaluated with the Mobile Analysis Platform (MAP) to determine platform performance for detecting respiratory viruses in samples previously characterized using clinical RT-PCR assays. The percent agreement between MAP and clinical results was 97% for influenza A (73/75), 100% (21/21) for influenza B, 100% (6/6) for RSV, and 80% (4/5) for negative specimens. The approximate LOD of the MAP was 30 copies/assay for RSV and 1500 copies/assay for MERS Coronavirus.",,"['Hardick, Justin', 'Metzgar, David', 'Risen, Lisa', 'Myers, Christopher', 'Balansay, Melinda', 'Malcom, Trent', 'Rothman, Richard', 'Gaydos, Charlotte']",,,,
,PMC,Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia,http://dx.doi.org/10.1016/j.ajhg.2018.01.019,PMC5985284,,,"Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of a surfactant-like substance in alveolar spaces and hypoxemic respiratory failure. Genetic PAP (GPAP) is caused by mutations in genes encoding surfactant proteins or genes encoding a surfactant phospholipid transporter in alveolar type II epithelial cells. GPAP is also caused by mutations in genes whose products are implicated in surfactant catabolism in alveolar macrophages (AMs). We performed whole-exome sequence analysis in a family affected by infantile-onset PAP with hypogammaglobulinemia without causative mutations in genes associated with PAP: SFTPB, SFTPC, ABCA3, CSF2RA, CSF2RB, and GATA2. We identified a heterozygous missense variation in OAS1, encoding 2,′5′-oligoadenylate synthetase 1 (OAS1) in three affected siblings, but not in unaffected family members. Deep sequence analysis with next-generation sequencing indicated 3.81% mosaicism of this variant in DNA from their mother’s peripheral blood leukocytes, suggesting that PAP observed in this family could be inherited as an autosomal-dominant trait from the mother. We identified two additional de novo heterozygous missense variations of OAS1 in two unrelated simplex individuals also manifesting infantile-onset PAP with hypogammaglobulinemia. PAP in the two simplex individuals resolved after hematopoietic stem cell transplantation, indicating that OAS1 dysfunction is associated with impaired surfactant catabolism due to the defects in AMs.",,"['Cho, Kazutoshi', 'Yamada, Masafumi', 'Agematsu, Kazunaga', 'Kanegane, Hirokazu', 'Miyake, Noriko', 'Ueki, Masahiro', 'Akimoto, Takuma', 'Kobayashi, Norimoto', 'Ikemoto, Satoru', 'Tanino, Mishie', 'Fujita, Atsushi', 'Hayasaka, Itaru', 'Miyamoto, Satoshi', 'Tanaka-Kubota, Mari', 'Nakata, Koh', 'Shiina, Masaaki', 'Ogata, Kazuhiro', 'Minakami, Hisanori', 'Matsumoto, Naomichi', 'Ariga, Tadashi']",,,,
,PMC,Metagenomic Sequencing Detects Respiratory Pathogens in Hematopoietic Cellular Transplant Patients,http://dx.doi.org/10.1164/rccm.201706-1097LE,PMC5821905,,,,,"['Langelier, Charles', 'Zinter, Matt S.', 'Kalantar, Katrina', 'Yanik, Gregory A.', 'Christenson, Stephanie', 'O’Donovan, Brian', 'White, Corin', 'Wilson, Michael', 'Sapru, Anil', 'Dvorak, Christopher C.', 'Miller, Steve', 'Chiu, Charles Y.', 'DeRisi, Joseph L.']",,,,
,PMC,The Emergency Medical Service Microbiome,http://dx.doi.org/10.1128/AEM.02098-17,PMC5812948,,,"Emergency medical services (EMS) personnel are an integral component of the health care framework and function to transport patients from various locations to and between care facilities. In addition to physical injury, EMS personnel are expected to be at high risk to acquire and transmit health care-associated infections (HAIs) in the workplace. However, currently, little is known about EMS biosafety risk factors and the epidemiological contribution of EMS to pathogen transmission within and outside the health care sector. Health care facility microbiomes contain diverse bacterial, fungal, and viral pathogens that cause over 1.7 million HAIs each year in the United States alone. While hospital microbiomes have been relatively well studied, there is scant information about EMS infrastructure and equipment microbiomes or the role(s) they play in HAI transmission between health care facilities. We review recent literature investigating the microbiome of ambulances and other EMS service facilities which consistently identify antibiotic-resistant pathogens causing HAIs, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus, and Klebsiella pneumoniae. Our review provides evidence that EMS microbiomes are dynamic and important pathogen reservoirs, and it underscores the need for more widespread and in-depth microbiome studies to elucidate patterns of pathogen transmission. We discuss emerging DNA sequencing technologies and other methods that can be applied to characterize and mitigate EMS biosafety risks in the future. Understanding the complex interplay between EMS and hospital microbiomes will provide key insights into pathogen transmission mechanisms and identify strategies to minimize HAIs and community infection.",,"['Hudson, Andrew J.', 'Glaister, Graeme D.', 'Wieden, Hans-Joachim']",,,,
,PMC,CRISPR/Cas9 knockout of USP18 enhances type I IFN responsiveness and restricts HIV-1 infection in macrophages,http://dx.doi.org/10.1002/JLB.3MIA0917-352R,PMC6754309,,,"The IFN-stimulated gene ubiquitin specific proteinase 18 (USP18) encodes a protein that negatively regulates T1 IFN signaling via stearic inhibition of JAK1 recruitment to the IFNα receptor 2 subunit (IFNAR2). Here we demonstrate that USP18 expression is induced by HIV-1 in a T1 IFN dependent manner. Experimental depletion of USP18 by CRISPR/Cas9 gene editing results in a significant restriction of HIV-1 replication in an induced pluripotent stem cell (iPSC)-derived macrophage model. In the absence of USP18, macrophages have increased responsiveness to stimulation with T1 IFNs with prolonged phosphorylation of STAT1 and STAT2 and increased expression of interferon-stimulated genes that are key for antiviral responses. Interestingly, HIV-1 requires some signaling through the T1 IFN receptor to replicate efficiently because a neutralizing antibody that inhibits T1 IFN activity reduces HIV-1 replication rate in monocyte-derived macrophages. USP18 induction by HIV-1 tunes the IFN response to optimal levels allowing for efficient transcription from the HIV-1 LTR promoter while minimizing the T1 IFN-induced antiviral response that would otherwise restrict viral replication and spread. Finally, iPSC and CRISPR/Cas9 gene targeting offer a powerful tool to study host factors that regulate innate immune responses.",,"['Taylor, Jared P.', 'Cash, Melanie N.', 'Santostefano, Katherine E.', 'Nakanishi, Mahito', 'Terada, Naohiro', 'Wallet, Mark A.']",,,,
,PMC,Characteristics and Outcomes of Coronavirus Infection in Children: The Role of Viral Factors and an Immunocompromised State,http://dx.doi.org/10.1093/jpids/pix093,PMC6437838,,,"BACKGROUND: Immunocompromised children might be predisposed to serious infections from human coronaviruses (HCoVs), including strains OC43, NL63, HKU1, and 229E; however, the virologic and clinical features of HCoV infection in immunocompromised children have not been compared to those in nonimmunocompromised children. METHODS: We retrospectively analyzed a cohort of children who presented to Seattle Children’s Hospital and in whom HCoV was detected by a multiplex respiratory polymerase chain reaction assay of a nasal sample between October 2012 and March 2016. Lower respiratory tract disease (LRTD) was defined as possible or definite infiltrate seen in chest imaging, need for oxygen, or abnormal lung examination in conjunction with a physician diagnosis of LRTD. We used logistic regression modeling to evaluate risk factors for LRTD and LRTD that necessitated oxygen use (severe LRTD), including an immunocompromised state, in children with HCoV infection. RESULTS: The median ages of 85 immunocompromised and 1152 nonimmunocompromised children with HCoV infection were 6.3 and 1.6 years, respectively. The prevalence of LRTD and of severe LRTD did not differ greatly between the immunocompromised and nonimmunocompromised patients (22% vs 26% [LRTD] and 15% vs 11% [severe LRTD], respectively); however, in a multivariable model, an immunocompromised state was associated with an increased likelihood of severe LRTD (adjusted odds ratio, 2.5 [95% confidence interval, 1.2–4.9]; P = .01). Younger age, having an underlying pulmonary disorder, and the presence of respiratory syncytial virus were also associated with LRTD or severe LRTD in multivariable models. The risks of LRTD or severe LRTD did not differ among the children with different HCoV strains. CONCLUSIONS: The presence of a copathogen and host factors, including an immunocompromised state, were associated with increased risk for severe LRTD. Recognizing risk factors for severe respiratory illness might assist in risk stratification.",,"['Ogimi, Chikara', 'Englund, Janet A', 'Bradford, Miranda C', 'Qin, Xuan', 'Boeckh, Michael', 'Waghmare, Alpana']",,,,
,PMC,Structural Basis for the Inhibition of Host Gene Expression by Porcine Epidemic Diarrhea Virus nsp1,http://dx.doi.org/10.1128/JVI.01896-17,PMC5809747,,,"Porcine epidemic diarrhea virus (PEDV), an enteropathogenic Alphacoronavirus, has caused enormous economic losses in the pork industry. Nonstructural protein 1 (nsp1) is a characteristic feature of alpha- and betacoronaviruses, which exhibits both functional conservation and mechanistic diversity in inhibiting host gene expression and antiviral responses. However, the detailed structure and molecular mechanisms underlying the Alphacoronavirus nsp1 inhibition of host gene expression remain unclear. Here, we report the first full-length crystal structure of Alphacoronavirus nsp1 from PEDV. The structure displays a six-stranded β-barrel fold in the middle of two α-helices. The core structure of PEDV nsp1 shows high similarity to those of severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 and transmissible gastroenteritis virus (TGEV) nsp1, despite its low degree of sequence homology. Using ribopuromycylation and Renilla luciferase reporter assays, we showed that PEDV nsp1 can dramatically inhibit general host gene expression. Furthermore, three motifs (amino acids [aa] 67 to 71, 78 to 85, and 103 to 110) of PEDV nsp1 create a stable functional region for inhibiting protein synthesis, differing considerably from Betacoronavirus nsp1. These results elucidate the detailed structural basis through which PEDV nsp1 inhibits host gene expression, providing insight into the development of a new attenuated vaccine with nsp1 modifications. IMPORTANCE Porcine epidemic diarrhea virus (PEDV) has led to tremendous economic losses in the global swine industry. PEDV nsp1 plays a crucial role in inhibiting host gene expression, but its functional mechanism remains unclear. Here, we report the full-length structure of PEDV nsp1, the first among coronaviruses to be reported. The 1.25-Å resolution crystal structure of PEDV nsp1 shows high similarity to severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1(13–128) and transmissible gastroenteritis virus (TGEV) nsp1(1–104), despite a lack of sequence homology. Structural and biochemical characterization demonstrated that PEDV nsp1 possesses a stable functional region for inhibition of host protein synthesis, which is formed by loops at residues 67 to 71, 78 to 85, and 103 to 110. The different functional regions in PEDV nsp1 and SARS-CoV nsp1 may explain their distinct mechanisms. Importantly, our structural data are conducive to understanding the mechanism of PEDV nsp1 inhibition of the expression of host genes and may aid in the development of a new attenuated vaccine.",,"['Shen, Zhou', 'Ye, Gang', 'Deng, Feng', 'Wang, Gang', 'Cui, Min', 'Fang, Liurong', 'Xiao, Shaobo', 'Fu, Zhen F.', 'Peng, Guiqing']",,,,
,PMC,Human Norovirus NS3 Has RNA Helicase and Chaperoning Activities,http://dx.doi.org/10.1128/JVI.01606-17,PMC5809735,,,"RNA-remodeling proteins, including RNA helicases and chaperones, act to remodel RNA structures and/or protein-RNA interactions and are required for all processes involving RNAs. Although many viruses encode RNA helicases and chaperones, their in vitro activities and their roles in infected cells largely remain elusive. Noroviruses are a diverse group of positive-strand RNA viruses in the family Caliciviridae and constitute a significant and potentially fatal threat to human health. Here, we report that the protein NS3 encoded by human norovirus has both ATP-dependent RNA helicase activity that unwinds RNA helices and ATP-independent RNA-chaperoning activity that can remodel structured RNAs and facilitate strand annealing. Moreover, NS3 can facilitate viral RNA synthesis in vitro by norovirus polymerase. NS3 may therefore play an important role in norovirus RNA replication. Lastly, we demonstrate that the RNA-remodeling activity of NS3 is inhibited by guanidine hydrochloride, an FDA-approved compound, and, more importantly, that it reduces the replication of the norovirus replicon in cultured human cells. Altogether, these findings are the first to demonstrate the presence of RNA-remodeling activities encoded by Caliciviridae and highlight the functional significance of NS3 in the noroviral life cycle. IMPORTANCE Noroviruses are a diverse group of positive-strand RNA viruses, which annually cause hundreds of millions of human infections and over 200,000 deaths worldwide. For RNA viruses, cellular or virus-encoded RNA helicases and/or chaperones have long been considered to play pivotal roles in viral life cycles. However, neither RNA helicase nor chaperoning activity has been demonstrated to be associated with any norovirus-encoded proteins, and it is also unknown whether norovirus replication requires the participation of any viral or cellular RNA helicases/chaperones. We found that a norovirus protein, NS3, not only has ATP-dependent helicase activity, but also acts as an ATP-independent RNA chaperone. Also, NS3 can facilitate in vitro viral RNA synthesis, suggesting the important role of NS3 in norovirus replication. Moreover, NS3 activities can be inhibited by an FDA-approved compound, which also suppresses norovirus replicon replication in human cells, raising the possibility that NS3 could be a target for antinoroviral drug development.",,"['Li, Teng-Feng', 'Hosmillo, Myra', 'Schwanke, Hella', 'Shu, Ting', 'Wang, Zhaowei', 'Yin, Lei', 'Curry, Stephen', 'Goodfellow, Ian G.', 'Zhou, Xi']",,,,
,PMC,Influenza A Virus Reassortment Is Limited by Anatomical Compartmentalization following Coinfection via Distinct Routes,http://dx.doi.org/10.1128/JVI.02063-17,PMC5809721,,,"Exchange of gene segments through reassortment is a major feature of influenza A virus evolution and frequently contributes to the emergence of novel epidemic, pandemic, and zoonotic strains. It has long been evident that viral diversification through reassortment is constrained by genetic incompatibility between divergent parental viruses. In contrast, the role of virus-extrinsic factors in determining the likelihood of reassortment has remained unclear. To evaluate the impact of such factors in the absence of confounding effects of segment mismatch, we previously reported an approach in which reassortment between wild-type (wt) and genetically tagged variant (var) viruses of the same strain is measured. Here, using wt/var systems in the A/Netherlands/602/2009 (pH1N1) and A/Panama/2007/99 (H3N2) strain backgrounds, we tested whether inoculation of parental viruses into distinct sites within the respiratory tract limits their reassortment. Using a ferret (Mustella putorius furo) model, either matched parental viruses were coinoculated intranasally or one virus was instilled intranasally whereas the second was instilled intratracheally. Dual intranasal inoculation resulted in robust reassortment for wt/var viruses of both strain backgrounds. In contrast, when infections were initiated simultaneously at distinct sites, strong compartmentalization of viral replication was observed and minimal reassortment was detected. The observed lack of viral spread between upper and lower respiratory tract tissues may be attributable to localized exclusion of superinfection within the host, mediated by innate immune responses. Our findings indicate that dual infections in nature are more likely to result in reassortment if viruses are seeded into similar anatomical locations and have matched tissue tropisms. IMPORTANCE Genetic exchange between influenza A viruses (IAVs) through reassortment can facilitate the emergence of antigenically drifted seasonal strains and plays a prominent role in the development of pandemics. Typical human influenza infections are concentrated in the upper respiratory tract; however, lower respiratory tract (LRT) infection is an important feature of severe cases, which are more common in the very young, the elderly, and individuals with underlying conditions. In addition to host factors, viral characteristics and mode of transmission can also increase the likelihood of LRT infection: certain zoonotic IAVs are thought to favor the LRT, and transmission via small droplets allows direct seeding into lower respiratory tract tissues. To gauge the likelihood of reassortment in coinfected hosts, we assessed the extent to which initiation of infection at distinct respiratory tract sites impacts reassortment frequency. Our results reveal that spatially distinct inoculations result in anatomical compartmentalization of infection, which in turn strongly limits reassortment.",,"['Richard, Mathilde', 'Herfst, Sander', 'Tao, Hui', 'Jacobs, Nathan T.', 'Lowen, Anice C.']",,,,
,PMC,STING-dependent translation inhibition restricts RNA virus replication,http://dx.doi.org/10.1073/pnas.1716937115,PMC5834695,,,"In mammalian cells, IFN responses that occur during RNA and DNA virus infections are activated by distinct signaling pathways. The RIG-I–like-receptors (RLRs) bind viral RNA and engage the adaptor MAVS (mitochondrial antiviral signaling) to promote IFN expression, whereas cGAS (cGMP–AMP synthase) binds viral DNA and activates an analogous pathway via the protein STING (stimulator of IFN genes). In this study, we confirm that STING is not necessary to induce IFN expression during RNA virus infection but also find that STING is required to restrict the replication of diverse RNA viruses. The antiviral activities of STING were not linked to its ability to regulate basal expression of IFN-stimulated genes, activate transcription, or autophagy. Using vesicular stomatitis virus as a model, we identified a requirement of STING to inhibit translation during infection and upon transfection of synthetic RLR ligands. This inhibition occurs at the level of translation initiation and restricts the production of viral and host proteins. The inability to restrict translation rendered STING-deficient cells 100 times more likely to support productive viral infections than wild-type counterparts. Genetic analysis linked RNA sensing by RLRs to STING-dependent translation inhibition, independent of MAVS. Thus, STING has dual functions in host defense, regulating protein synthesis to prevent RNA virus infection and regulating IFN expression to restrict DNA viruses.",,"['Franz, Kate M.', 'Neidermyer, William J.', 'Tan, Yee-Joo', 'Whelan, Sean P. J.', 'Kagan, Jonathan C.']",,,,
,PMC,Comparison of the performance of laboratory tests in the diagnosis of feline infectious peritonitis,http://dx.doi.org/10.1177/1040638718756460,PMC6505812,,,"We compared the performance of clinicopathologic and molecular tests used in the antemortem diagnosis of feline infectious peritonitis (FIP). From 16 FIP and 14 non-FIP cats, we evaluated retrospectively the sensitivity, specificity, and likelihood ratios (LRs) of serum protein electrophoresis, α(1)-acid glycoprotein (AGP) on peripheral blood, screening reverse-transcription nested PCR (RT-nPCR) on the 3’–untranslated region (3’-UTR), and spike (S) gene sequencing on peripheral blood, body cavity effusions, and tissue, as well as body cavity cytology and delta total nucleated cell count (ΔTNC). Any of these tests on blood, and especially the molecular tests, may support or confirm a clinical diagnosis of FIP. A negative result does not exclude the disease except for AGP. Cytology, 3’-UTR PCR, and ΔTNC may confirm a clinical diagnosis on effusions; cytology or 3’-UTR PCR may exclude FIP. Conversely, S gene sequencing is not recommended based on the LRs. On tissues, S gene sequencing is preferable when histology is highly consistent with FIP, and 3’-UTR PCR when FIP is unlikely. Combining one test with high LR+ with one with low LR− (e.g., molecular tests and AGP on blood, ΔTNC and cytology in effusions) may improve the diagnostic power of the most used laboratory tests.",,"['Stranieri, Angelica', 'Giordano, Alessia', 'Paltrinieri, Saverio', 'Giudice, Chiara', 'Cannito, Valentina', 'Lauzi, Stefania']",,,,
,PMC,A retrospective study of the neuropathology and diagnosis of naturally occurring feline infectious peritonitis,http://dx.doi.org/10.1177/1040638718755833,PMC6505806,,,"Feline infectious peritonitis (FIP) is one of the most important viral diseases of cats worldwide. Our study describes the neuropathology and the diagnostic features of 26 cases of FIP in domestic cats. The average age of affected individuals was 11.8 mo, and there was no sex or breed predisposition. Clinical neurologic signs were noted in 22 cases, and rabies was clinically suspected in 11 cases. Twenty cats had lesions in multiple organs, and 6 cats had lesions only in the brain. Gross neuropathologic changes occurred in 15 cases and consisted of hydrocephalus (10 cases), cerebellar herniation through the foramen magnum (6 cases), cerebral swelling with flattening of gyri (2 cases), and accumulation of fibrin within ventricles (2 cases) or leptomeninges (1 case). Histologically, 3 main distinct distributions of neuropathologic changes were observed, namely periventricular encephalitis (12 cases), rhombencephalitis (8 cases), and diffuse leptomeningitis with superficial encephalitis (6 cases). Fresh tissue samples were submitted for fluorescent antibody testing (FAT) after autopsy in 17 cases, and positive results were found in only 7 cases. Immunohistochemistry (IHC) for feline coronavirus confirmed the diagnosis in all 26 cases. IHC appears to be a more sensitive and reliable test for confirmation of FIP than is FAT.",,"Rissi, Daniel R.",,,,
,PMC,Why Enveloped Viruses Need Cores—The Contribution of a Nucleocapsid Core to Viral Budding,http://dx.doi.org/10.1016/j.bpj.2017.11.3782,PMC5985022,,,"During the lifecycle of many enveloped viruses, a nucleocapsid core buds through the cell membrane to acquire an outer envelope of lipid membrane and viral glycoproteins. However, the presence of a nucleocapsid core is not required for assembly of infectious particles. To determine the role of the nucleocapsid core, we develop a coarse-grained computational model with which we investigate budding dynamics as a function of glycoprotein and nucleocapsid interactions, as well as budding in the absence of a nucleocapsid. We find that there is a transition between glycoprotein-directed budding and nucleocapsid-directed budding that occurs above a threshold strength of nucleocapsid interactions. The simulations predict that glycoprotein-directed budding leads to significantly increased size polydispersity and particle polymorphism. This polydispersity can be explained by a theoretical model accounting for the competition between bending energy of the membrane and the glycoprotein shell. The simulations also show that the geometry of a budding particle leads to a barrier to subunit diffusion, which can result in a stalled, partially budded state. We present a phase diagram for this and other morphologies of budded particles. Comparison of these structures against experiments could establish bounds on whether budding is directed by glycoprotein or nucleocapsid interactions. Although our model is motivated by alphaviruses, we discuss implications of our results for other enveloped viruses.",,"['Lázaro, Guillermo R.', 'Mukhopadhyay, Suchetana', 'Hagan, Michael F.']",,,,
,PMC,Development and validation of a probe hybridization reverse-transcription quantitative PCR for detection of mamastrovirus 2 in domestic cats,http://dx.doi.org/10.1177/1040638717753963,PMC6505809,,,"Astroviruses are viral pathogens that have been associated with enteric and neurologic disease in a variety of species. The domestic cat is a prominent host, with reports of astroviral infection being both highly prevalent and widely distributed in the feline population. Despite the potential for inducing significant disease, especially within shelter environments, there is currently only one reliable method of detection: standard reverse-transcription PCR using pan-astrovirus degenerate primers (consensus RT-PCR) with product sequencing. Unfortunately, this process is relatively slow and costly. Quantitative real-time PCR (qPCR) represents an efficient, economical alternative, with the added benefit of viral load quantification. We developed a RT-qPCR assay using probe hybridization technique to detect conserved regions of mamastrovirus 2 extracted from fecal samples of domestic cats. Known positive and negative samples were tested, and results were compared with gold standard consensus RT-PCR and sequencing. A standard curve was employed to determine limits of detection. In order to assess analytic specificity, we tested several additional samples that had been collected from non-felid species and were known to contain non-target astroviruses. Discrepant results between consensus RT-PCR and RT-qPCR testing were further analyzed with a validation RT-PCR assay, using mamastrovirus 2–specific primers. Our probe hybridization RT-qPCR assay is reliable and effective for the detection of mamastrovirus 2. This assay will allow rapid, affordable detection and facilitate further research on astroviral infection within domestic cats.",,"['Williams, Hannah G.', 'Cook, Kirstin A.', 'Lawler, Patricia E.', 'Archer, Linda L.', 'Schaedel, Karen', 'Isaza, Natalie', 'Wellehan, James F. X.']",,,,
,PMC,Repurposing of Kinase Inhibitors as Broad-Spectrum Antiviral Drugs,http://dx.doi.org/10.1089/dna.2017.4033,PMC5804095,,,The high cost of drug development and the narrow spectrum of coverage typically provided by direct-acting antivirals limit the scalability of this antiviral approach. This review summarizes progress and challenges in the repurposing of approved kinase inhibitors as host-targeted broad-spectrum antiviral therapies.,,"['Schor, Stanford', 'Einav, Shirit']",,,,
,PMC,"Infectious disease-specific health literacy in Tibet, China",http://dx.doi.org/10.1093/heapro/daw054,PMC5831159,,,"This study was aimed to develop an instrument to assess infectious disease-specific health literacy (IDSHL) in the general population of Tibet, China and identify the association between IDSHL and reported infectious disease-related symptoms. A survey using a standardized questionnaire, which included 25 questions on knowledge, behaviors and skills regarding infectious diseases, was conducted in the general population of Tibet, China between September 2011 and November 2011. The 25 questions formed the index system of the instrument assessing IDSHL (total scores: 25 scores). Factors associated with index scores of IDSHL were identified by general linear model. The association between the index score of IDSHL and the occurrence of the five selected infectious disease symptoms (fever, diarrhea, rash, jaundice or conjunctivitis) were investigated using multivariate unconditional logistic regression. Among 5717 eligible participants in the survey, 4631 participants completed all of the 25 questions in the instrument. The instrument was reliable and valid as measured by the Cronbach’s alpha coefficient and split-half coefficient, and the confirmatory factor analysis. Only 1.0% (48/4631) answered ≥80% of the 25 questions correctly (score ≥20). Significant factors associated with lower health literacy score included female gender, older age, Tibetan group, lower education level, underlying diseases and more undeveloped area. For each increasing score of IDSHL, reports of fever, diarrhea or jaundice in the prior year were significantly decreased by 3% (p = 0.015), 4% (p = 0.004) and 16% (p < 0.001), respectively. Accurately measuring IDSHL could help identify those individuals with poor IDSHL, who could be targeted with specific interventions to improve health.",,"['Yang, Peng', 'Dunzhu, Ciren', 'Widdowson, Marc-Alain', 'Wu, Shuangsheng', 'Ciren, Pengcuo', 'Duoji, Dunzhu', 'Pingcuo, Wangqing', 'Dun, Bian', 'Ma, Chunna', 'Li, Jie', 'Pang, Xinghuo', 'Wang, Quanyi']",,,,
,PMC,Rhinovirus in Febrile Infants and Risk of Bacterial Infection,http://dx.doi.org/10.1542/peds.2017-2384,PMC5810600,,,"BACKGROUND: Febrile infants with viral respiratory infections have a reduced risk of bacterial infection compared with virus-negative infants. The risk of concomitant bacterial infection in febrile infants positive for human rhinovirus (HRV) by polymerase chain reaction (PCR) is unknown. METHODS: Infants 1–90 days old managed using the care process model for well-appearing febrile infants and with respiratory viral testing by PCR (RVPCR) in the emergency department or inpatient setting of 22 hospitals in the Intermountain Healthcare system from 2007-2016 were identified. Relative risk (RR) of bacterial infection was calculated for infants with HRV, non-HRV viruses, or no virus detected. RESULTS: Of 10 964 febrile infants identified, 4037 (37%) had RVPCR. Of these, 2212 (55%) were positive for a respiratory virus; 1392 (35%) for HRV alone. Bacterial infection was identified in 9.5%. Febrile infants with HRV detected were more likely to have bacterial infection than those with non-HRV viruses (7.8% vs 3.7%; P < .001; RR 2.12 [95% CI 1.43–3.15]). Risk of urinary tract infection was not significantly different for HRV-positive infants at any age, nor was risk of invasive bacterial infection (IBI; bacteremia and/or meningitis) meaningfully different for infants 1–28 day olds. Infants 29–90 days old with HRV had a decreased likelihood of IBI (RR 0.52 [95% CI 0.34–0.80]). CONCLUSIONS: HRV is common in febrile infants. Detection did not alter risk of concomitant urinary tract infection at any age or risk of IBI in infants 1–28 days old. HRV detection may be relevant in considering risk of IBI for infants 29–90 days of age.",,"['Blaschke, Anne J.', 'Korgenski, E. Kent', 'Wilkes, Jacob', 'Presson, Angela P.', 'Thorell, Emily A.', 'Pavia, Andrew T.', 'Knackstedt, Elizabeth D.', 'Reynolds, Carolyn', 'Schunk, Jeff E.', 'Daly, Judy A.', 'Byington, Carrie L.']",,,,
,PMC,"An ultraprocessive, accurate reverse transcriptase encoded by a metazoan group II intron",http://dx.doi.org/10.1261/rna.063479.117,PMC5769746,,,"Group II introns and non-LTR retrotransposons encode a phylogenetically related family of highly processive reverse transcriptases (RTs) that are essential for mobility and persistence of these retroelements. Recent crystallographic studies on members of this RT family have revealed that they are structurally distinct from the retroviral RTs that are typically used in biotechnology. However, quantitative, structure-guided analysis of processivity, efficiency, and accuracy of this alternate RT family has been lacking. Here, we characterize the processivity of a group II intron maturase RT from Eubacterium rectale (E.r.), for which high-resolution structural information is available. We find that the E.r. maturase RT (MarathonRT) efficiently copies transcripts at least 10 kb in length and displays superior intrinsic RT processivity compared to commercial enzymes such as Superscript IV (SSIV). The elevated processivity of MarathonRT is at least partly mediated by a loop structure in the finger subdomain that acts as a steric guard (the α-loop). Additionally, we find that a positively charged secondary RNA binding site on the surface of the RT diminishes the primer utilization efficiency of the enzyme, and that reengineering of this surface enhances capabilities of the MarathonRT. Finally, using single-molecule sequencing, we show that the error frequency of MarathonRT is comparable to that of other high-performance RTs, such as SSIV, which were tested in parallel. Our results provide a structural framework for understanding the enhanced processivity of retroelement RTs, and they demonstrate the potential for engineering a powerful new generation of RT tools for application in biotechnology and research.",,"['Zhao, Chen', 'Liu, Fei', 'Pyle, Anna Marie']",,,,
,PMC,Therapeutics discovery: From bench to first in-human trials*,http://dx.doi.org/10.3892/br.2018.1052,PMC5854938,,,"The ‘Therapeutics discovery: From bench to first in-human trials’ conference, held at the King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), Kingdom of Saudi Arabia (KSA) from October 10–12, 2017, provided a unique opportunity for experts worldwide to discuss advances in drug discovery and development, focusing on phase I clinical trials. It was the first event of its kind to be hosted at the new research center, which was constructed to boost drug discovery and development in the KSA in collaboration with institutions, such as the Academic Drug Discovery Consortium in the United States of America (USA), Structural Genomics Consortium of the University of Oxford in the United Kingdom (UK), and Institute of Materia Medica of the Chinese Academy of Medical Sciences in China. The program was divided into two parts. A pre-symposium day took place on October 10, during which courses were conducted on clinical trials, preclinical drug discovery, molecular biology and nanofiber research. The attendees had the opportunity for one-to-one meetings with international experts to exchange information and foster collaborations. In the second part of the conference, which took place on October 11 and 12, the clinical trials pipeline, design and recruitment of volunteers, and economic impact of clinical trials were discussed. The Saudi Food and Drug Administration presented the regulations governing clinical trials in the KSA. The process of preclinical drug discovery from small molecules, cellular and immunologic therapies, and approaches to identifying new targets were also presented. The recommendation of the conference was that researchers in the KSA must invest more fund, talents and infrastructure to lead the region in phase I clinical trials and preclinical drug discovery. Diseases affecting the local population, such as Middle East Respiratory Syndrome and resistant bacterial infections, represent the optimal starting point.",,"['Al-Hujaily, Ensaf M.', 'Khatlani, Tanvir', 'Alehaideb, Zeyad', 'Ali, Rizwan', 'Almuzaini, Bader', 'Alrfaei, Bahauddeen M', 'Iqbal, Jahangir', 'Islam, Imadul', 'Malik, Shuja', 'Marwani, Bader A', 'Massadeh, Salam', 'Nehdi, Atef', 'Alsomaie, Barrak', 'Debasi, Bader', 'Bushnak, Ibraheem', 'Noibi, Saeed', 'Hussain, Syed', 'Wajid, Wahid Abdul', 'Armand, Jean-Pierre', 'Gul, Sheraz', 'Oyarzabal, Julen', 'Rais, Rana', 'Bountra, Chas', 'Alaskar, Ahmed', 'Knawy, Bander Al', 'Boudjelal, Mohamed']",,,,
,PMC,Experimental Adaptive Evolution of Simian Immunodeficiency Virus SIVcpz to Pandemic Human Immunodeficiency Virus Type 1 by Using a Humanized Mouse Model,http://dx.doi.org/10.1128/JVI.01905-17,PMC5790958,,,"Human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS, originated from simian immunodeficiency virus from chimpanzees (SIVcpz), the precursor of the human virus, approximately 100 years ago. This indicates that HIV-1 has emerged through the cross-species transmission of SIVcpz from chimpanzees to humans. However, it remains unclear how SIVcpz has evolved into pandemic HIV-1 in humans. To address this question, we inoculated three SIVcpz strains (MB897, EK505, and MT145), four pandemic HIV-1 strains (NL4-3, NLCSFV3, JRCSF, and AD8), and two nonpandemic HIV-1 strains (YBF30 and DJO0131). Humanized mice infected with SIVcpz strain MB897, a virus phylogenetically similar to pandemic HIV-1, exhibited a peak viral load comparable to that of mice infected with pandemic HIV-1, while peak viral loads of mice infected with SIVcpz strain EK505 or MT145 as well as nonpandemic HIV-1 strains were significantly lower. These results suggest that SIVcpz strain MB897 is preadapted to humans, unlike the other SIVcpz strains. Moreover, viral RNA sequencing of MB897-infected humanized mice identified a nonsynonymous mutation in env, a G413R substitution in gp120. The infectivity of the gp120 G413R mutant of MB897 was significantly higher than that of parental MB897. Furthermore, we demonstrated that the gp120 G413R mutant of MB897 augments the capacity for viral replication in both in vitro cell cultures and humanized mice. Taken together, this is the first experimental investigation to use an animal model to demonstrate a gain-of-function evolution of SIVcpz into pandemic HIV-1. IMPORTANCE From the mid-20th century, humans have been exposed to the menace of infectious viral diseases, such as severe acute respiratory syndrome coronavirus, Ebola virus, and Zika virus. These outbreaks of emerging/reemerging viruses can be triggered by cross-species viral transmission from wild animals to humans, or zoonoses. HIV-1, the causative agent of AIDS, emerged by the cross-species transmission of SIVcpz, the HIV-1 precursor in chimpanzees, around 100 years ago. However, the process by which SIVcpz evolved to become HIV-1 in humans remains unclear. Here, by using a hematopoietic stem cell-transplanted humanized-mouse model, we experimentally recapitulate the evolutionary process of SIVcpz to become HIV-1. We provide evidence suggesting that a strain of SIVcpz, MB897, preadapted to infect humans over other SIVcpz strains. We further demonstrate a gain-of-function evolution of SIVcpz in infected humanized mice. Our study reveals that pandemic HIV-1 has emerged through at least two steps: preadaptation and subsequent gain-of-function mutations.",,"['Sato, Kei', 'Misawa, Naoko', 'Takeuchi, Junko S.', 'Kobayashi, Tomoko', 'Izumi, Taisuke', 'Aso, Hirofumi', 'Nagaoka, Shumpei', 'Yamamoto, Keisuke', 'Kimura, Izumi', 'Konno, Yoriyuki', 'Nakano, Yusuke', 'Koyanagi, Yoshio']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.02180-17,PMC5790956,,,,,,,,,
,PMC,Cryo-Electron Microscopy Structure of Porcine Deltacoronavirus Spike Protein in the Prefusion State,http://dx.doi.org/10.1128/JVI.01556-17,PMC5790952,,,"Coronavirus spike proteins from different genera are divergent, although they all mediate coronavirus entry into cells by binding to host receptors and fusing viral and cell membranes. Here, we determined the cryo-electron microscopy structure of porcine deltacoronavirus (PdCoV) spike protein at 3.3-Å resolution. The trimeric protein contains three receptor-binding S1 subunits that tightly pack into a crown-like structure and three membrane fusion S2 subunits that form a stalk. Each S1 subunit contains two domains, an N-terminal domain (S1-NTD) and C-terminal domain (S1-CTD). PdCoV S1-NTD has the same structural fold as alpha- and betacoronavirus S1-NTDs as well as host galectins, and it recognizes sugar as its potential receptor. PdCoV S1-CTD has the same structural fold as alphacoronavirus S1-CTDs, but its structure differs from that of betacoronavirus S1-CTDs. PdCoV S1-CTD binds to an unidentified receptor on host cell surfaces. PdCoV S2 is locked in the prefusion conformation by structural restraint of S1 from a different monomeric subunit. PdCoV spike possesses several structural features that may facilitate immune evasion by the virus, such as its compact structure, concealed receptor-binding sites, and shielded critical epitopes. Overall, this study reveals that deltacoronavirus spikes are structurally and evolutionally more closely related to alphacoronavirus spikes than to betacoronavirus spikes; it also has implications for the receptor recognition, membrane fusion, and immune evasion by deltacoronaviruses as well as coronaviruses in general. IMPORTANCE In this study, we determined the cryo-electron microscopy structure of porcine deltacoronavirus (PdCoV) spike protein at a 3.3-Å resolution. This is the first atomic structure of a spike protein from the deltacoronavirus genus, which is divergent in amino acid sequences from the well-studied alpha- and betacoronavirus spike proteins. Here, we described the overall structure of the PdCoV spike and the detailed structure of each of its structural elements. Moreover, we analyzed the functions of each of the structural elements. Based on the structures and functions of these structural elements, we discussed the evolution of PdCoV spike protein in relation to the spike proteins from other coronavirus genera. This study combines the structure, function, and evolution of PdCoV spike protein and provides many insights into its receptor recognition, membrane fusion, and immune evasion.",,"['Shang, Jian', 'Zheng, Yuan', 'Yang, Yang', 'Liu, Chang', 'Geng, Qibin', 'Tai, Wanbo', 'Du, Lanying', 'Zhou, Yusen', 'Zhang, Wei', 'Li, Fang']",,,,
,PMC,A Proteomics Survey of Junín Virus Interactions with Human Proteins Reveals Host Factors Required for Arenavirus Replication,http://dx.doi.org/10.1128/JVI.01565-17,PMC5790945,,,"Arenaviruses are negative-strand, enveloped RNA viruses that cause significant human disease. In particular, Junín mammarenavirus (JUNV) is the etiologic agent of Argentine hemorrhagic fever. At present, little is known about the cellular proteins that the arenavirus matrix protein (Z) hijacks to accomplish its various functions, including driving the process of virus release. Furthermore, there is little knowledge regarding host proteins incorporated into arenavirus particles and their importance for virion function. To address these deficiencies, we used mass spectrometry to identify human proteins that (i) interact with the JUNV matrix protein inside cells or within virus-like particles (VLPs) and/or (ii) are incorporated into bona fide JUNV strain Candid#1 particles. Bioinformatics analyses revealed that multiple classes of human proteins were overrepresented in the data sets, including ribosomal proteins, Ras superfamily proteins, and endosomal sorting complex required for transport (ESCRT) proteins. Several of these proteins were required for the propagation of JUNV (ADP ribosylation factor 1 [ARF1], ATPase, H(+) transporting, lysosomal 38-kDa, V0 subunit d1 [ATP6V0D1], and peroxiredoxin 3 [PRDX3]), lymphocytic choriomeningitis mammarenavirus (LCMV) (Rab5c), or both viruses (ATP synthase, H(+) transporting, mitochondrial F1 complex, beta polypeptide [ATP5B] and IMP dehydrogenase 2 [IMPDH2]). Furthermore, we show that the release of infectious JUNV particles, but not LCMV particles, requires a functional ESCRT pathway and that ATP5B and IMPDH2 are required for JUNV budding. In summary, we have provided a large-scale map of host machinery that associates with JUNV and identified key human proteins required for its propagation. This data set provides a resource for the field to guide antiviral target discovery and to better understand the biology of the arenavirus matrix protein and the importance of host proteins for virion function. IMPORTANCE Arenaviruses are deadly human pathogens for which there are no U.S. Food and Drug Administration-approved vaccines and only limited treatment options. Little is known about the host proteins that are incorporated into arenavirus particles or that associate with its multifunctional matrix protein. Using Junín mammarenavirus (JUNV), the causative agent of Argentine hemorrhagic fever, as a model organism, we mapped the human proteins that are incorporated into JUNV particles or that associate with the JUNV matrix protein. Functional analysis revealed host machinery that is required for JUNV propagation, including the cellular ESCRT pathway. This study improves our understanding of critical arenavirus-host interactions and provides a data set that will guide future studies to better understand arenavirus pathogenesis and identify novel host proteins that can be therapeutically targeted.",,"['Ziegler, Christopher M.', 'Eisenhauer, Philip', 'Kelly, Jamie A.', 'Dang, Loan N.', 'Beganovic, Vedran', 'Bruce, Emily A.', 'King, Benjamin R.', 'Shirley, David J.', 'Weir, Marion E.', 'Ballif, Bryan A.', 'Botten, Jason']",,,,
,PMC,Type III Interferon Restriction by Porcine Epidemic Diarrhea Virus and the Role of Viral Protein nsp1 in IRF1 Signaling,http://dx.doi.org/10.1128/JVI.01677-17,PMC5790939,,,"Type III interferons (IFNs) play a vital role in maintaining the antiviral state of the mucosal epithelial surface in the gut, and in turn, enteric viruses may have evolved to evade the type III IFN responses during infection. To study the possible immune evasion of the type III IFN response by porcine epidemic diarrhea virus (PEDV), a line of porcine intestinal epithelial cells was developed as a cell model for PEDV replication. IFN-λ1 and IFN-λ3 inhibited PEDV replication, indicating the anti-PEDV activity of type III IFNs. Of the 21 PEDV proteins, nsp1, nsp3, nsp5, nsp8, nsp14, nsp15, nsp16, open reading frame 3 (ORF3), E, M, and N were found to suppress type III IFN activities, and IRF1 (interferon regulatory factor 1) signaling mediated the suppression. PEDV specifically inhibited IRF1 nuclear translocation. The peroxisome is the innate antiviral signaling platform for the activation of IRF1-mediated IFN-λ production, and the numbers of peroxisomes were found to be decreased in PEDV-infected cells. PEDV nsp1 blocked the nuclear translocation of IRF1 and reduced the number of peroxisomes to suppress IRF1-mediated type III IFNs. Mutational studies showed that the conserved residues of nsp1 were crucial for IRF1-mediated IFN-λ suppression. Our study for the first time provides evidence that the porcine enteric virus PEDV downregulates and evades IRF1-mediated type III IFN responses by reducing the number of peroxisomes. IMPORTANCE Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric coronavirus that emerged in swine in the United States and has caused severe economic losses. PEDV targets intestinal epithelial cells in the gut, and intestinal epithelial cells selectively induce and respond to the production of type III interferons (IFNs). However, little is known about the modulation of the type III IFN response by PEDV in intestinal epithelial cells. In this study, we established a porcine intestinal epithelial cell model for PEDV replication. We found that PEDV inhibited IRF1-mediated type III IFN production by decreasing the number of peroxisomes in porcine intestinal epithelial cells. We also demonstrated that the conserved residues in the PEDV nsp1 protein were crucial for IFN suppression. This study for the first time shows PEDV evasion of the type III IFN response in intestinal epithelial cells, and it provides valuable information on host cell-virus interactions not only for PEDV but also for other enteric viral infections in swine.",,"['Zhang, Qingzhan', 'Ke, Hanzhong', 'Blikslager, Anthony', 'Fujita, Takashi', 'Yoo, Dongwan']",,,,
,PMC,Inhibition of Cytosolic Phospholipase A(2)α Impairs an Early Step of Coronavirus Replication in Cell Culture,http://dx.doi.org/10.1128/JVI.01463-17,PMC5790932,,,"Coronavirus replication is associated with intracellular membrane rearrangements in infected cells, resulting in the formation of double-membrane vesicles (DMVs) and other membranous structures that are referred to as replicative organelles (ROs). The latter provide a structural scaffold for viral replication/transcription complexes (RTCs) and help to sequester RTC components from recognition by cellular factors involved in antiviral host responses. There is increasing evidence that plus-strand RNA (+RNA) virus replication, including RO formation and virion morphogenesis, affects cellular lipid metabolism and critically depends on enzymes involved in lipid synthesis and processing. Here, we investigated the role of cytosolic phospholipase A(2)α (cPLA(2)α) in coronavirus replication using a low-molecular-weight nonpeptidic inhibitor, pyrrolidine-2 (Py-2). The inhibition of cPLA(2)α activity, which produces lysophospholipids (LPLs) by cleaving at the sn-2 position of phospholipids, had profound effects on viral RNA and protein accumulation in human coronavirus 229E-infected Huh-7 cells. Transmission electron microscopy revealed that DMV formation in infected cells was significantly reduced in the presence of the inhibitor. Furthermore, we found that (i) viral RTCs colocalized with LPL-containing membranes, (ii) cellular LPL concentrations were increased in coronavirus-infected cells, and (iii) this increase was diminished in the presence of the cPLA(2)α inhibitor Py-2. Py-2 also displayed antiviral activities against other viruses representing the Coronaviridae and Togaviridae families, while members of the Picornaviridae were not affected. Taken together, the study provides evidence that cPLA(2)α activity is critically involved in the replication of various +RNA virus families and may thus represent a candidate target for broad-spectrum antiviral drug development. IMPORTANCE Examples of highly conserved RNA virus proteins that qualify as drug targets for broad-spectrum antivirals remain scarce, resulting in increased efforts to identify and specifically inhibit cellular functions that are essential for the replication of RNA viruses belonging to different genera and families. The present study supports and extends previous conclusions that enzymes involved in cellular lipid metabolism may be tractable targets for broad-spectrum antivirals. We obtained evidence to show that a cellular phospholipase, cPLA2α, which releases fatty acid from the sn-2 position of membrane-associated glycerophospholipids, is critically involved in coronavirus replication, most likely by producing lysophospholipids that are required to form the specialized membrane compartments in which viral RNA synthesis takes place. The importance of this enzyme in coronavirus replication and DMV formation is supported by several lines of evidence, including confocal and electron microscopy, viral replication, and lipidomics studies of coronavirus-infected cells treated with a highly specific cPLA(2)α inhibitor.",,"['Müller, Christin', 'Hardt, Martin', 'Schwudke, Dominik', 'Neuman, Benjamin W.', 'Pleschka, Stephan', 'Ziebuhr, John']",,,,
,PMC,Glycan Shield and Fusion Activation of a Deltacoronavirus Spike Glycoprotein Fine-Tuned for Enteric Infections,http://dx.doi.org/10.1128/JVI.01628-17,PMC5790929,,,"Coronaviruses recently emerged as major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome. They utilize the spike (S) glycoprotein anchored in the viral envelope to mediate host attachment and fusion of the viral and cellular membranes to initiate infection. The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response. We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus. Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts. The structure further reveals a shortened S(2)′ activation loop, containing a reduced number of basic amino acids, which participates in rendering the spike largely protease resistant. This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity. IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes. We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide. Structural and glycoproteomics data reveal that PDCoV S is decorated with 78 N-linked glycans obstructing the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus. PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.",,"['Xiong, Xiaoli', 'Tortorici, M. Alejandra', 'Snijder, Joost', 'Yoshioka, Craig', 'Walls, Alexandra C.', 'Li, Wentao', 'McGuire, Andrew T.', 'Rey, Félix A.', 'Bosch, Berend-Jan', 'Veesler, David']",,,,
,PMC,Passive immunotherapy of viral infections: ‘super-antibodies’ enter the fray,http://dx.doi.org/10.1038/nri.2017.148,PMC5918154,,,"Antibodies have been used for more than 100 years in the therapy of infectious diseases but a new generation of highly potent and/or broadly cross-reactive human monoclonal antibodies (sometimes referred to as ‘super-antibodies’) offers new opportunities for intervention. The isolation of these antibodies, which are often rarely induced in human infections, has primarily been achieved by large-scale screening for suitable donors and new single B cell approaches to human monoclonal antibody generation. Engineering the antibodies to improve half-life and effector functions has further augmented their in vivo activity in some cases. Super-antibodies offer promise for the prophylaxis and therapy of infections with a range of viruses, including those that are highly antigenically variable and those that are newly emerging or have pandemic potential. The next few years will be decisive in the realization of the promise of super-antibodies.",,"['Walker, Laura M.', 'Burton, Dennis R.']",,,,
,PMC,PNAS Plus Significance Statements,http://dx.doi.org/10.1073/pnas.ss1155,PMC5798395,,,,,,,,,
,PMC,A modified HLA-A*0201-restricted CTL epitope from human oncoprotein (hPEBP4) induces more efficient antitumor responses,http://dx.doi.org/10.1038/cmi.2017.155,PMC6141579,,,"We previously identified human phosphatidylethanolamine-binding protein 4 (hPEBP4) as an antiapoptotic protein with increased expression levels in breast, ovarian and prostate cancer cells, but low expression levels in normal tissues, which makes hPEBP4 an attractive target for immunotherapy. Here, we developed hPEBP4-derived immunogenic peptides for inducing antigen-specific cytotoxic T lymphocytes (CTLs) targeting breast cancer. A panel of hPEBP4-derived peptides predicted by peptide-MHC-binding algorithms was evaluated to characterize their HLA-A2.1 affinity and immunogenicity. We identified a novel immunogenic peptide, P40–48 (TLFCQGLEV), that was capable of eliciting specific CTL responses in HLA-A2.1/K(b) transgenic mice, as well as in peripheral blood lymphocytes from breast cancer patients. Furthermore, amino-acid substitutions in the P40–48 sequence improved its immunogenicity against hPEBP4, a self-antigen, thus circumventing tolerance. We designed peptide analogs by preferred auxiliary HLA-A*0201 anchor residue replacement, which induced CTLs that were crossreactive to the native peptide. Several analogs were able to stably bind to HLA-A*0201 and elicit specific CTL responses better than the native sequence. Importantly, adoptive transfer of CTLs induced by vaccination with two analogs more effectively inhibited tumor growth than the native peptide. These data indicate that peptide analogs with high immunogenicity represent promising candidates for peptide-mediated therapeutic cancer vaccines.",,"['Sun, Weihong', 'Shi, Junyi', 'Wu, Jian', 'Zhang, Junchu', 'Chen, Huabiao', 'Li, Yuanyuan', 'Liu, Shuxun', 'Wu, Yanfeng', 'Tian, Zhigang', 'Cao, Xuetao', 'Li, Nan']",,,,
,PMC,Microglia are required for protection against lethal coronavirus encephalitis in mice,http://dx.doi.org/10.1172/JCI97229,PMC5824854,,,"Recent findings have highlighted the role of microglia in orchestrating normal development and refining neural network connectivity in the healthy CNS. Microglia are not only vital cells in maintaining CNS homeostasis, but also respond to injury, infection, and disease by undergoing proliferation and changes in transcription and morphology. A better understanding of the specific role of microglia in responding to viral infection is complicated by the presence of nonmicroglial myeloid cells with potentially overlapping function in the healthy brain and by the rapid infiltration of hematopoietic myeloid cells into the brain in diseased states. Here, we used an inhibitor of colony-stimulating factor 1 receptor (CSF1R) that depletes microglia to examine the specific roles of microglia in response to infection with the mouse hepatitis virus (MHV), a neurotropic coronavirus. Our results show that microglia were required during the early days after infection to limit MHV replication and subsequent morbidity and lethality. Additionally, microglia depletion resulted in ineffective T cell responses. These results reveal nonredundant, critical roles for microglia in the early innate and virus-specific T cell responses and for subsequent host protection from viral encephalitis.",,"['Wheeler, D. Lori', 'Sariol, Alan', 'Meyerholz, David K.', 'Perlman, Stanley']",,,,
,PMC,Porcine epidemic diarrhea virus reduces feed efficiency in nursery pigs,http://dx.doi.org/10.1093/jas/skx005,PMC6140930,,,"Porcine epidemic diarrhea virus (PEDV) infects enterocytes and in nursery pigs, results in diarrhea, anorexia, and reduced performance. Therefore, the objective of this study was to determine how PEDV infection influenced growth performance and repartitioning of amino acids and energy in nursery pigs. A total of 32 barrows and gilts, approximately 1 wk post-wean (BW = 8.46 ± 0.50 kg), and naïve for PEDV were obtained, weighed, and allotted based on sex and BW to one of two treatments: 1) Control, PEDV naïve and 2) PEDV-inoculated (PEDV) with eight pens of two pigs each per treatment. On day post-inoculation (dpi) 0, PEDV pigs were inoculated via intragastric gavage with PEDV isolate (USA/Iowa/18984/2013). Pig and feeder weights were recorded at dpi −7, 0, 5, and 20 in order to calculate ADG, ADFI, and G:F. Eight pigs per treatment were euthanized on dpi 5 and 20, and tissues and blood were collected. At dpi 5, all PEDV pigs were PCR positive for PEDV in feces. Overall, PEDV pigs tended (P < 0.10) to increase ADFI, which resulted in reduced (P < 0.05) feed efficiency. At dpi 5, PEDV pigs had reduced (P < 0.05) villus height and increased (P < 0.05) stem cell proliferation in the jejunum compared with Control pigs. Pigs inoculated with PEDV had increased (P < 0.05) serum haptoglobin and increased insulin-to-glucose ratios compared with Control pigs at dpi 5. Markers of muscle proteolysis were not different (P > 0.05) between treatments within dpi; however, at dpi 5, 20S proteasome activity was increased (P < 0.05) in longissimus dorsi of PEDV pigs compared with Control pigs. Liver and jejunum gluconeogenic enzyme activities were not different (P > 0.05) between treatments within dpi. Overall, PEDV-inoculated pigs did recover the absorptive capacity that was reduced during PEDV infection by increasing proliferation of intestinal stem cells. However, the energy and nutrients needed to recover the epithelium may be originating from available luminal nutrients instead of muscle proteolysis and gluconeogenesis. This study provides insight into the effects of an enteric coronavirus on postabsorptive metabolism in nursery pigs.",,"['Curry, S M', 'Burrough, E R', 'Schwartz, K J', 'Yoon, K J', 'Lonergan, S M', 'Gabler, N K']",,,,
,PMC,"Uncoupling proteins 1 and 2 (UCP1 and UCP2) from Arabidopsis thaliana are mitochondrial transporters of aspartate, glutamate, and dicarboxylates",http://dx.doi.org/10.1074/jbc.RA117.000771,PMC5857996,,,"The Arabidopsis thaliana genome contains 58 members of the solute carrier family SLC25, also called the mitochondrial carrier family, many of which have been shown to transport specific metabolites, nucleotides, and cofactors across the mitochondrial membrane. Here, two Arabidopsis members of this family, AtUCP1 and AtUCP2, which were previously thought to be uncoupling proteins and hence named UCP1/PUMP1 and UCP2/PUMP2, respectively, are assigned with a novel function. They were expressed in bacteria, purified, and reconstituted in phospholipid vesicles. Their transport properties demonstrate that they transport amino acids (aspartate, glutamate, cysteine sulfinate, and cysteate), dicarboxylates (malate, oxaloacetate, and 2-oxoglutarate), phosphate, sulfate, and thiosulfate. Transport was saturable and inhibited by mercurials and other mitochondrial carrier inhibitors to various degrees. AtUCP1 and AtUCP2 catalyzed a fast counterexchange transport as well as a low uniport of substrates, with transport rates of AtUCP1 being much higher than those of AtUCP2 in both cases. The aspartate/glutamate heteroexchange mediated by AtUCP1 and AtUCP2 is electroneutral, in contrast to that mediated by the mammalian mitochondrial aspartate glutamate carrier. Furthermore, both carriers were found to be targeted to mitochondria. Metabolite profiling of single and double knockouts shows changes in organic acid and amino acid levels. Notably, AtUCP1 and AtUCP2 are the first reported mitochondrial carriers in Arabidopsis to transport aspartate and glutamate. It is proposed that the primary function of AtUCP1 and AtUCP2 is to catalyze an aspartate(out)/glutamate(in) exchange across the mitochondrial membrane and thereby contribute to the export of reducing equivalents from the mitochondria in photorespiration.",,"['Monné, Magnus', 'Daddabbo, Lucia', 'Gagneul, David', 'Obata, Toshihiro', 'Hielscher, Björn', 'Palmieri, Luigi', 'Miniero, Daniela Valeria', 'Fernie, Alisdair R.', 'Weber, Andreas P. M.', 'Palmieri, Ferdinando']",,,,
,PMC,U.S. High-Level Isolation Unit Clinical Laboratory Capabilities Update,http://dx.doi.org/10.1128/JCM.01608-17,PMC5786736,,,"In late 2014, 56 hospitals in the United States were designated by state and federal public health authorities as specially designed high-level isolation units (HLIUs) equipped with advanced infrastructure, laboratory capabilities, and trained staff to care for patients with highly hazardous communicable diseases (HHCDs), such as Ebola virus disease. This survey describes the clinical laboratory support capabilities of U.S. HLIUs, including the specific test menus that HLIUs have identified to safely manage HHCD patients and the locations where such testing would be performed. In spring 2016, a survey was electronically distributed, as a fillable pdf file, to the 56 U.S. HLIUs. Site representatives completed the surveys, and data were coded and analyzed in an electronic spreadsheet, using descriptive statistics. Thirty-six HLIUs (64%) responded, and 33 completed the laboratory capabilities section. Thirty-one HLIUs (94%) had performed risk analyses for all laboratory procedures and equipment. Twenty-nine (88%) had decontamination procedures specified for all laboratory equipment used for patients with suspected or confirmed HHCDs. On-site laboratories in 27 HLIUs (81%) had the capacity to inventory and to securely store HHCD patient specimens. Ten HLIUs (31%) had at least one test they would conduct within the patient isolation room. The high-risk nature of HHCDs and the occupational exposures that may occur in clinical laboratories demand advanced preparation and risk assessment of work practices, laboratory equipment, and instrumentation by HLIU laboratories. Although risk analyses of clinical laboratory testing and equipment that HLIUs have conducted have likely focused on those for Ebola virus, HLIUs must be prepared to revise their current procedures for other HHCDs.",,"['Herstein, Jocelyn J.', 'Iwen, Peter C.', 'Jelden, Katelyn C.', 'Biddinger, Paul D.', 'Gibbs, Shawn G.', 'Le, Aurora B.', 'Hewlett, Angela L.', 'Lowe, John J.']",,,,
,PMC,Development of novel vaccine vectors: Chimpanzee adenoviral vectors,http://dx.doi.org/10.1080/21645515.2017.1419108,PMC6067905,,,"Adenoviral vector has been employed as one of the most efficient means against infectious diseases and cancer. It can be genetically modified and armed with foreign antigens to elicit specific antibody responses and T cell responses in hosts as well as engineered to induce apoptosis in cancer cells. The chimpanzee adenovirus-based vector is one kind of novel vaccine carriers whose unique features and non-reactivity to pre-existing human adenovirus neutralizing antibodies makes it an outstanding candidate for vaccine research and development. Here, we review the different strategies for constructing chimpanzee adenoviral vectors and their applications in recent clinical trials and also discuss the oncolytic virotherapy and immunotherapy based on chimpanzee adenoviral vectors.",,"['Guo, Jingao', 'Mondal, Moumita', 'Zhou, Dongming']",,,,
,PMC,What Is a Host? Attributes of Individual Susceptibility,http://dx.doi.org/10.1128/IAI.00636-17,PMC5778373,,,"In every epidemic some individuals become sick and some may die, whereas others recover from illness and still others show no signs or symptoms of disease. These differences highlight a fundamental question of microbial pathogenesis: why are some individuals susceptible to infectious diseases while others who acquire the same microbe remain well? For most of human history, the answer assumed the hand of providence. With the advent of the germ theory of disease, the focus on disease causality became the microbe, but this did not explain how there can be different outcomes of infection in different individuals with the same microbe. Here we examine the attributes of susceptibility in the context of the “damage-response framework” of microbial pathogenesis. We identify 11 attributes that, although not independent, are sufficiently distinct to be considered separately: microbiome, inoculum, sex, temperature, environment, age, chance, history, immunity, nutrition, and genetics. We use the first letter of each to create the mnemonic MISTEACHING, underscoring the need for caution in accepting dogma and attributing disease causality to any single factor. For both populations and individuals, variations in the attributes that assemble into MISTEACHING can create an enormity of combinations that can in turn translate into different outcomes of host-microbe encounters. Combinatorial diversity among the 11 attributes makes identifying “signatures” of susceptibility possible. However, with their inevitable uncertainties and propensity to change, there may still be a low likelihood for prediction with regard to individual host-microbe interactions, although probabilistic prediction may be possible.",,"['Casadevall, Arturo', 'Pirofski, Liise-anne']",,,,
,PMC,Therapeutic potential of porcine bronchoalveolar fluid-derived mesenchymal stromal cells in a pig model of LPS-induced ALI,http://dx.doi.org/10.1002/jcp.26397,PMC5878711,,,"In this study, we isolated mesenchymal stromal (stem) cells (MSCs) from broncho-alveolar lavage fluid (BAL) of 2-6 week-old commercial pigs. BAL-MSCs displayed fibroblastic morphology and possessed self-renewal properties. Similar to bone-marrow MSCs, BAL-MSCs expressed mesenchymal markers and both cell types lacked the expression of hematopoetic markers. BAL-MSCs, when cultured in differentiation induction media, differentiated into adipocytes, osteocytes and chondrocytes. Next, we examined if BAL-MSCs have the ability to treat lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a pig model. Five-week-old commercial pigs were inoculated intra-tracheally with E. coli LPS [(1 mg/kg body weight (b.wt.)].Twelve hours after the LPS inoculation, groups of pigs were inoculated intra-tracheally with BM-MSCs or BAL-MSCs (2×10(6) cells/kg b.wt.). Forty eight hours after the cells administration pigs were euthanized and neutrophils in BAL, lung lesions, and cytokines in lung lysates, and engraftment of MSCs in lungs were examined. Engraftment of BAL-MSCs in injured lungs was significantly higher than the BM-MSCs, however, both cell types were equally effective in attenuating LPS-induced ALI as evidenced by decreased inflammation, lung lesions and proinflammatory cytokines in the lungs of pigs treated with BAL-or BM-MSCs. These data in a preclinical large animal model suggest that BAL-MSCs may be used in clinical settings to treat ALI in humans.",,"['Khatri, Mahesh', 'Richardson, Levi Arthur']",,,,
,PMC,Poor outcome with hematopoietic stem cell transplantation for bone marrow failure and MDS with severe MIRAGE syndrome phenotype,http://dx.doi.org/10.1182/bloodadvances.2017012682,PMC5787871,,,Success of hematopoietic stem cell transplantation for MIRAGE syndrome may be limited by syndrome-specific comorbidities. SAMD9 mutations associated with MIRAGE syndrome are a newly described cause of congenital amegakaryocytic thrombocytopenia.,,"['Sarthy, Jay', 'Zha, Ji', 'Babushok, Daria', 'Shenoy, Archana', 'Fan, Jian-Meng', 'Wertheim, Gerald', 'Himebauch, Adam', 'Munchel, Ashley', 'Taraseviciute, Agne', 'Yang, Samuel', 'Shima, Hirohito', 'Narumi, Satoshi', 'Meshinchi, Soheil', 'Olson, Timothy S.']",,,,
,PMC,β-d-N(4)-Hydroxycytidine Is a Potent Anti-alphavirus Compound That Induces a High Level of Mutations in the Viral Genome,http://dx.doi.org/10.1128/JVI.01965-17,PMC5774879,,,"Venezuelan equine encephalitis virus (VEEV) is a representative member of the New World alphaviruses. It is transmitted by mosquito vectors and causes highly debilitating disease in humans, equids, and other vertebrate hosts. Despite a continuous public health threat, very few compounds with anti-VEEV activity in cell culture and in mouse models have been identified to date, and rapid development of virus resistance to some of them has been recorded. In this study, we investigated the possibility of using a modified nucleoside analog, β-d-N(4)-hydroxycytidine (NHC), as an anti-VEEV agent and defined the mechanism of its anti-VEEV activity. The results demonstrate that NHC is a very potent antiviral agent. It affects both the release of genome RNA-containing VEE virions and their infectivity. Both of these antiviral activities are determined by the NHC-induced accumulation of mutations in virus-specific RNAs. The antiviral effect is most prominent when NHC is applied early in the infectious process, during the amplification of negative- and positive-strand RNAs in infected cells. Most importantly, only a low-level resistance of VEEV to NHC can be developed, and it requires acquisition and cooperative function of more than one mutation in nsP4. These adaptive mutations are closely located in the same segment of nsP4. Our data suggest that NHC is more potent than ribavirin as an anti-VEEV agent and likely can be used to treat other alphavirus infections. IMPORTANCE Venezuelan equine encephalitis virus (VEEV) can cause widespread epidemics among humans and domestic animals. VEEV infections result in severe meningoencephalitis and long-term sequelae. No approved therapeutics exist for treatment of VEEV infections. Our study demonstrates that β-d-N(4)-hydroxycytidine (NHC) is a very potent anti-VEEV compound, with the 50% effective concentration being below 1 μM. The mechanism of NHC antiviral activity is based on induction of high mutation rates in the viral genome. Accordingly, NHC treatment affects both the rates of particle release and the particle infectivity. Most importantly, in contrast to most of the anti-alphavirus drugs that are under development, resistance of VEEV to NHC develops very inefficiently. Even low levels of resistance require acquisition of multiple mutations in the gene of the VEEV-specific RNA-dependent RNA polymerase nsP4.",,"['Urakova, Nadya', 'Kuznetsova, Valeriya', 'Crossman, David K.', 'Sokratian, Arpine', 'Guthrie, David B.', 'Kolykhalov, Alexander A.', 'Lockwood, Mark A.', 'Natchus, Michael G.', 'Crowley, Michael R.', 'Painter, George R.', 'Frolova, Elena I.', 'Frolov, Ilya']",,,,
,PMC,Entry of Human Coronavirus NL63 into the Cell,http://dx.doi.org/10.1128/JVI.01933-17,PMC5774871,,,"The first steps of human coronavirus NL63 (HCoV-NL63) infection were previously described. The virus binds to target cells by use of heparan sulfate proteoglycans and interacts with the ACE2 protein. Subsequent events, including virus internalization and trafficking, remain to be elucidated. In this study, we mapped the process of HCoV-NL63 entry into the LLC-Mk2 cell line and ex vivo three-dimensional (3D) tracheobronchial tissue. Using a variety of techniques, we have shown that HCoV-NL63 virions require endocytosis for successful entry into the LLC-MK2 cells, and interaction between the virus and the ACE2 molecule triggers recruitment of clathrin. Subsequent vesicle scission by dynamin results in virus internalization, and the newly formed vesicle passes the actin cortex, which requires active cytoskeleton rearrangement. Finally, acidification of the endosomal microenvironment is required for successful fusion and release of the viral genome into the cytoplasm. For 3D tracheobronchial tissue cultures, we also observed that the virus enters the cell by clathrin-mediated endocytosis, but we obtained results suggesting that this pathway may be bypassed. IMPORTANCE Available data on coronavirus entry frequently originate from studies employing immortalized cell lines or undifferentiated cells. Here, using the most advanced 3D tissue culture system mimicking the epithelium of conductive airways, we systematically mapped HCoV-NL63 entry into susceptible cells. The data obtained allow for a better understanding of the infection process and may support development of novel treatment strategies.",,"['Milewska, Aleksandra', 'Nowak, Paulina', 'Owczarek, Katarzyna', 'Szczepanski, Artur', 'Zarebski, Miroslaw', 'Hoang, Agnieszka', 'Berniak, Krzysztof', 'Wojarski, Jacek', 'Zeglen, Slawomir', 'Baster, Zbigniew', 'Rajfur, Zenon', 'Pyrc, Krzysztof']",,,,
,PMC,Funding vaccines for emerging infectious diseases,http://dx.doi.org/10.1080/21645515.2017.1412024,PMC6067896,,,"Immunization has played a large role in substantially reducing the infected and death tolls from infectious diseases. In the case of emerging diseases, the identity of the pathogen responsible, as well as the time and location for the next outbreak, cannot be accurately predicted using current means. Coupled with disjointed efforts towards the development of vaccines and a lack of funds and desire to advance promising products against known emerging pathogens to clinical trials, there has been a shortage of approved products ready for emergency use. Recent outbreaks have exposed these weaknesses, and the Coalition for Epidemic Preparedness Innovations (CEPI) was created in 2016 to address these issues. In this commentary, we discuss the establishment of such a global vaccine fund, and provide some additional points to consider for stimulating further discussion on this comprehensive, ambitious initiative.",,"['Wong, Gary', 'Qiu, Xiangguo']",,,,
,PMC,Emerging Roles of Inflammasomes in Acute Pneumonia,http://dx.doi.org/10.1164/rccm.201707-1391PP,PMC5768907,,,,,"['Ravi Kumar, Sangeetha', 'Paudel, Sagar', 'Ghimire, Laxman', 'Bergeron, Scott', 'Cai, Shanshan', 'Zemans, Rachel L.', 'Downey, Gregory P.', 'Jeyaseelan, Samithamby']",,,,
,PMC,Melatonin regulates CRE-dependent gene transcription underlying osteoblast proliferation by activating Src and PKA in parallel,,PMC5801349,,,"Several studies have indicated a relationship between melatonin and idiopathic scoliosis, including our previous work which demonstrated that melatonin can inhibit osteoblast proliferation; however, the mechanism remains unclear. Here, we utilized a MTT assay to show that melatonin significantly reduces osteoblast proliferation in a concentration-and time-dependent manner. Through a combination of techniques, including real-time PCR, MTT assays, immunofluorescence, and luciferase assays, we confirmed that melatonin-induced changes in phosphorylated cAMP response element-binding protein (CREB) reduced transcriptional activity in a melatonin receptor-dependent manner. Surprisingly, treatment of osteoblasts with the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) inhibitor PD98059 up-regulated other cascades upstream of CREB. We next treated cells with PKA and Src inhibitors and observed that melatonin can also activate the protein kinase A (PKA) and Src pathways. To examine whether Src is upstream from the cAMP-PKA pathway, we measured cAMP levels in response to melatonin with and without a Src inhibitor (PP2) and found that PP2 had no additional effect. Therefore, the transcription-dependent mechanisms involved in CREB phosphorylation, along with melatonin, activated Src via a parallel signaling pathway that was separate from that of PKA. Finally, we transfected osteoblasts with lentiviral CREB short hairpin (sh) RNAs and found a decrease in the expression of proliferating cell nuclear antigen (PCNA) and osteoblast proliferation. These results suggest that CREB and PCNA are downstream targets of melatonin signaling, and that the down-regulation of CREB, which is regulated via PKA and Src pathways, contributes to the melatonin-induced inhibition of osteoblast proliferation.",,"['Tao, Lin', 'Zhu, Yue']",,,,
,PMC,Using Genome Sequence to Enable the Design of Medicines and Chemical Probes,http://dx.doi.org/10.1021/acs.chemrev.7b00504,PMC5989578,,,"Rapid progress in genome sequencing technology has put us firmly into a postgenomic era. A key challenge in biomedical research is harnessing genome sequence to fulfill the promise of personalized medicine. This Review describes how genome sequencing has enabled the identification of disease-causing biomolecules and how these data have been converted into chemical probes of function, preclinical lead modalities, and ultimately U.S. Food and Drug Administration (FDA)-approved drugs. In particular, we focus on the use of oligonucleotide-based modalities to target disease-causing RNAs; small molecules that target DNA, RNA, or protein; the rational repurposing of known therapeutic modalities; and the advantages of pharmacogenetics. Lastly, we discuss the remaining challenges and opportunities in the direct utilization of genome sequence to enable design of medicines.",,"['Angelbello, Alicia J.', 'Chen, Jonathan L.', 'Childs-Disney, Jessica L.', 'Zhang, Peiyuan', 'Wang, Zi-Fu', 'Disney, Matthew D.']",,,,
,PMC,Molecular detection and characterization of transient bovine viral diarrhea virus (BVDV) infections in cattle commingled with ten BVDV persistently infected cattle,http://dx.doi.org/10.1177/1040638717753962,PMC6505824,,,"Fifty-three cattle of unknown serologic status that were not persistently infected (PI) with bovine viral diarrhea virus (BVDV) were commingled with 10 cattle that were PI with different strains of BVDV, and were monitored for an extended commingle period using a reverse-transcription real-time PCR (RT-rtPCR) BVDV assay on various sample types. Transient infections with BVDV were also assessed by virus isolation, virus neutralization (VN) assays, and direct buffy coat 5′-UTR sequencing. Infections were demonstrated in all cattle by RT-rtPCR; however, the detection rate was dependent on the type of sample. Buffy coat samples demonstrated a significantly greater number of positive results (p ≤ 0.05) than either serum or nasal swab samples. Presence of elevated BVDV VN titers at the onset inversely correlated with the number of test days positive that an individual would be identified by RT-rtPCR from buffy coat samples, and directly correlated with the average Ct values accumulated over all RT-rtPCR test days from buffy coat samples. Both single and mixed genotype/subgenotype/strain infections were detected in individual cattle by direct sample 5′-UTR sequencing. A BVDV-2a strain from a PI animal was found to be the predominant strain infecting 64% of all non-PI cattle; BVDV-1b strains originating from 3 PI cattle were never detected in non-PI cattle. Although direct sample 5′-UTR sequencing was capable of demonstrating mixed BVDV infections, identifying all strains suspected was not always efficient or possible.",,"['Peddireddi, Lalitha', 'Foster, Kelly A.', 'Poulsen, Elizabeth G.', 'An, Baoyan', 'Hoang, Quoc Hung', 'O’Connell, Catherine', 'Anderson, Joseph W.', 'Thomson, Daniel U.', 'Hanzlicek, Gregg A.', 'Bai, Jianfa', 'Hesse, Richard A.', 'Oberst, Richard D.', 'Anderson, Gary A.', 'Leyva-Baca, Ivan']",,,,
,PMC,Nasopharyngeal Lactobacillus is associated with a reduced risk of childhood wheezing illnesses following acute respiratory syncytial virus infection in infancy,http://dx.doi.org/10.1016/j.jaci.2017.10.049,PMC6039278,,,"BACKGROUND: Early life acute respiratory infection (ARI) with respiratory syncytial virus (RSV) has been strongly associated with the development of childhood wheezing illnesses, but the pathways underlying this association are poorly understood. OBJECTIVE: To examine the role of the nasopharyngeal microbiome in the development of childhood wheezing illnesses following RSV ARI in infancy. METHODS: We conducted a nested cohort study of 118 previously healthy, term infants with confirmed RSV ARI by RT-PCR. We used next-generation sequencing of the V4 region of the 16S ribosomal RNA gene to characterize the nasopharyngeal microbiome during RSVARI. Our main outcome of interest was 2-year subsequent wheeze. RESULTS: Of the 118 infants, 113 (95.8%) had 2-year outcome data. Of these, 46 (40.7%) had parental report of subsequent wheeze. There was no association between the overall taxonomic composition, diversity, and richness of the nasopharyngeal microbiome during RSV ARI with the development of subsequent wheeze. However, the nasopharyngeal detection and abundance of Lactobacillus was consistently higher in infants who did not develop this outcome. Lactobacillus also ranked first among the different genera in a model distinguishing infants with and without subsequent wheeze. CONCLUSIONS: The nasopharyngeal detection and increased abundance of Lactobacillus during RSV ARI in infancy are associated with a reduced risk of childhood wheezing illnesses at age 2 years.",,"['Rosas-Salazar, Christian', 'Shilts, Meghan H.', 'Tovchigrechko, Andrey', 'Schobel, Seth', 'Chappell, James D.', 'Larkin, Emma K.', 'Gebretsadik, Tebeb', 'Halpin, Rebecca A.', 'Nelson, Karen E.', 'Moore, Martin L.', 'Anderson, Larry J.', 'Peebles, R. Stokes', 'Das, Suman R.', 'Hartert, Tina V.']",,,,
,PMC,Macrocyclic θ-defensins suppress tumor necrosis factor-α (TNF-α) shedding by inhibition of TNF-α–converting enzyme,http://dx.doi.org/10.1074/jbc.RA117.000793,PMC5827436,,,"Theta-defensins (θ-defensins) are macrocyclic peptides expressed exclusively in granulocytes and selected epithelia of Old World monkeys. They contribute to anti-pathogen host defense responses by directly killing a diverse range of microbes. Of note, θ-defensins also modulate microbe-induced inflammation by affecting the production of soluble tumor necrosis factor (sTNF) and other proinflammatory cytokines. Here, we report that natural rhesus macaque θ-defensin (RTD) isoforms regulate sTNF cellular release by inhibiting TNF-α–converting enzyme (TACE; also known as a disintegrin and metalloprotease 17; ADAM17), the primary pro-TNF sheddase. Dose-dependent inhibition of cellular TACE activity by RTDs occurred when leukocytes were stimulated with live Escherichia coli cells as well as numerous Toll-like receptor agonists. Moreover, the relative inhibitory potencies of the RTD isoforms strongly correlated with their suppression of TNF release by stimulated blood leukocytes and THP-1 monocytes. RTD isoforms also inhibited ADAM10, a sheddase closely related to TACE. TACE inhibition was abrogated by introducing a single opening in the RTD-1 backbone, demonstrating that the intact macrocycle is required for enzyme inhibition. Enzymologic analyses showed that RTD-1 is a fast binding, reversible, non-competitive inhibitor of TACE. We conclude that θ-defensin–mediated inhibition of pro-TNF proteolysis by TACE represents a rapid mechanism for the regulation of sTNF and TNF-dependent inflammatory pathways. Molecules with structural and functional features mimicking those of θ-defensins may have clinical utility as TACE inhibitors for managing TNF-driven diseases.",,"['Schaal, Justin B.', 'Maretzky, Thorsten', 'Tran, Dat Q.', 'Tran, Patti A.', 'Tongaonkar, Prasad', 'Blobel, Carl P.', 'Ouellette, André J.', 'Selsted, Michael E.']",,,,
,PMC,A randomized placebo-controlled phase 1 safety and tolerability study of a novel human anti-MERS coronavirus polyclonal intravenous immunoglobulin produced from transchromosomic cattle,http://dx.doi.org/10.1016/S1473-3099(18)30002-1,PMC5871563,,,"BACKGROUND: Passive immunotherapy approaches are being developed to prevent and treat a variety of human medical conditions. Here we report the first use of a fully-human polyclonal IgG immunoglobulin (SAB-301) produced from hyperimmune plasma of transchromosomic (Tc) cattle immunized with a Middle East Respiratory Syndrome (MERS) coronavirus vaccine. METHODS: We conducted a double-blind, placebo-controlled, single dose escalation study in six cohorts of 3–10 participants who were randomly assigned by a computer-generated table to receive 1, 2.5, 5, 10, 20, or 50 mg/kg of SAB-301 or placebo on Day 0, and were followed by clinical, laboratory, and pharmacokinetic assessments on days 1, 3, 7, 21, 42 and 90. The primary outcome was safety whereas pharmacokinetic profile, MERS virus neutralization assay over time (pharmacodynamics), and immunogenicity were secondary outcomes. The analysis was performed on the intention to treat population. ClinicalTrials.gov Identifier: NCT02788188. FINDINGS: We randomized 38 participants (28 to SAB-301 and 10 to placebo). Ninety-seven adverse event (AEs) were reported: 64 AEs occurred in 23 of 28 participants (82%) receiving SAB-301 (mean 2.3 AEs per participant), and 33 AEs occurred in 10 of 10 participants (100%) receiving placebo (mean 3.3 AEs per participant). The most common AEs were headache, albuminuria, elevated creatine kinase, and common cold, and occurred in similar proportions as placebo. Single dose pharmacokinetics (PK) demonstrated relatively linear and dose-proportional increases in maximal concentration and area-under-the-concentration-time curve (AUC(0–24)), and the PK strongly correlated with the microneutralization assay (R(2)=0.845, p<0.001). The AUC in the 50 mg/kg dose (27498.18 μg*days/mL) is comparable to the AUC that was associated with protection in a preclinical model. The average terminal elimination half-life (t(1/2)) was ~ 28 days. INTERPRETATION: Single infusions of SAB-301 up to 50 mg/kg appear to be safe and well-tolerated in healthy participants. Tc cattle derived human immunoglobulin offers a new platform technology to produce fully-human polyclonal IgG immunoglobulin for other medical conditions. FUNDING: National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States.",,"['Beigel, John H.', 'Voell, Jocelyn', 'Kumar, Parag', 'Raviprakash, Kanakatte', 'Wu, Hua', 'Jiao, Jin-An', 'Sullivan, Eddie', 'Luke, Thomas', 'Davey, Richard T.']",,,,
,PMC,PNAS Plus Significance Statements,http://dx.doi.org/10.1073/pnas.ss1152,PMC5777089,,,,,,,,,
,PMC,The role of adjuvant immunomodulatory agents for treatment of severe influenza,http://dx.doi.org/10.1016/j.antiviral.2018.01.002,PMC5801167,,,"A severe inflammatory immune response with hypercytokinemia occurs in patients hospitalized with severe influenza, such as avian influenza A(H5N1), A(H7N9), and seasonal A(H1N1)pdm09 virus infections. The role of immunomodulatory therapy is unclear as there have been limited published data based on randomized controlled trials (RCTs). Passive immunotherapy such as convalescent plasma and hyperimmune globulin have some studies demonstrating benefit when administered as an adjunctive therapy for severe influenza. Triple combination of oseltamivir, clarithromycin, and naproxen for severe influenza has one study supporting its use, and confirmatory studies would be of great interest. Likewise, confirmatory studies of sirolimus without concomitant corticosteroid therapy should be explored as a research priority. Other agents with potential immunomodulating effects, including non-immune intravenous immunoglobulin, N-acetylcysteine, acute use of statins, macrolides, pamidronate, nitazoxanide, chloroquine, antiC5a antibody, interferons, human mesenchymal stromal cells, mycophenolic acid, peroxisome proliferator-activated receptors agonists, non-steroidal anti-inflammatory agents, mesalazine, herbal medicine, and the role of plasmapheresis and hemoperfusion as rescue therapy have supportive preclinical or observational clinical data, and deserve more investigation preferably by RCTs. Systemic corticosteroids administered in high dose may increase the risk of mortality and morbidity in patients with severe influenza and should not be used, while the clinical utility of low dose systemic corticosteroids requires further investigation.",,"['Hui, David S', 'Lee, Nelson', 'Chan, Paul K', 'Beigel, John H']",,,,
,PMC,Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation,http://dx.doi.org/10.1096/fj.201700747RR,PMC5901386,29295864,CC BY-NC,"A novel protein-folding function of RNA has been recognized, which can outperform previously known molecular chaperone proteins. The RNA as a molecular chaperone (chaperna) activity is intrinsic to some ribozymes and is operational during viral infections. Our purpose was to test whether influenza hemagglutinin (HA) can be assembled in a soluble, trimeric, and immunologically activating conformation by means of an RNA molecular chaperone (chaperna) activity. An RNA-interacting domain (RID) from the host being immunized was selected as a docking tag for RNA binding, which served as a transducer for the chaperna function for de novo folding and trimeric assembly of RID-HA1. Mutations that affect tRNA binding greatly increased the soluble aggregation defective in trimer assembly, suggesting that RNA interaction critically controls the kinetic network in the folding/assembly pathway. Immunization of mice resulted in strong hemagglutination inhibition and high titers of a neutralizing antibody, providing sterile protection against a lethal challenge and confirming the immunologically relevant HA conformation. The results may be translated into a rapid response to a new influenza pandemic. The harnessing of the novel chaperna described herein with immunologically tailored antigen-folding functions should serve as a robust prophylactic and diagnostic tool for viral infections.—Yang, S. W., Jang, Y. H., Kwon, S. B., Lee, Y. J., Chae, W., Byun, Y. H., Kim, P., Park, C., Lee, Y. J., Kim, C. K., Kim, Y. S., Choi, S. I., Seong, B. L. Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation.",2018 May 8,"['Yang, Seung Won', 'Jang, Yo Han', 'Kwon, Soon Bin', 'Lee, Yoon Jae', 'Chae, Wonil', 'Byun, Young Ho', 'Kim, Paul', 'Park, Chan', 'Lee, Young Jae', 'Kim, Choon Kang', 'Kim, Young Seok', 'Choi, Seong Il', 'Seong, Baik Lin']",FASEB J,,,
,PMC,Varicella zoster meningitis: an atypical case of zoster reactivation in immunocompetent young adult,http://dx.doi.org/10.1136/bcr-2017-223257,PMC5775783,,,"Varicella virus is a neurotropic virus that can reactivate later in life to cause zoster or shingles. Typically, it affects elderly, immunocompromised population. We report an unusual case of an immunocompetent young adult presenting with occipital headache and zoster rash, without preherpetic and postherpetic neuralgia, who was diagnosed with varicella meningitis on Polymerase chain reaction (PCR). He was treated with intravenous acyclovir and later discharged on famciclovir. Diagnosis of varicella meningitis is difficult in the absence of typical features of zoster rash and requires high index of suspicion. Rapid diagnostic tests including varicella PCR and antithecal antibody testing can help in the confirmation of varicella zoster meningitis.",,"['Khaliq, Muhammad Farhan', 'Kochar, Tanureet', 'John, Molly']",,,,
,PMC,Infectious complications of CD19-targeted chimeric antigen receptor–modified T-cell immunotherapy,http://dx.doi.org/10.1182/blood-2017-07-793760,PMC5755046,,,"Lymphodepletion chemotherapy with CD19-targeted chimeric antigen receptor–modified T (CAR-T)-cell immunotherapy is a novel treatment for refractory or relapsed B-cell malignancies. Infectious complications of this approach have not been systematically studied. We evaluated infections occurring between days 0 to 90 in 133 patients treated with CD19 CAR-T cells in a phase 1/2 study. We used Poisson and Cox regression to evaluate pre- and posttreatment risk factors for infection, respectively. The cohort included patients with acute lymphoblastic leukemia (ALL; n = 47), chronic lymphocytic leukemia (n = 24), and non-Hodgkin lymphoma (n = 62). There were 43 infections in 30 of 133 patients (23%) within 28 days after CAR–T-cell infusion with an infection density of 1.19 infections for every 100 days at risk. There was a lower infection density of 0.67 between days 29 and 90 (P = .02). The first infection occurred a median of 6 days after CAR–T-cell infusion. Six patients (5%) developed invasive fungal infections and 5 patients (4%) had life-threatening or fatal infections. Patients with ALL, ≥4 prior antitumor regimens, and receipt of the highest CAR–T-cell dose (2 × 10(7) cells per kg) had a higher infection density within 28 days in an adjusted model of baseline characteristics. Cytokine release syndrome (CRS) severity was the only factor after CAR–T-cell infusion associated with infection in a multivariable analysis. The incidence of infections was comparable to observations from clinical trials of salvage chemoimmunotherapies in similar patients. This trial was registered at www.clinicaltrials.gov as #NCT01865617.",,"['Hill, Joshua A.', 'Li, Daniel', 'Hay, Kevin A.', 'Green, Margaret L.', 'Cherian, Sindhu', 'Chen, Xueyan', 'Riddell, Stanley R.', 'Maloney, David G.', 'Boeckh, Michael', 'Turtle, Cameron J.']",,,,
,PMC,An “Old” Protein with A New Story: Coronavirus Endoribonuclease Is Important for Evading Host Antiviral Defenses,http://dx.doi.org/10.1016/j.virol.2017.12.024,PMC5869138,,,"Here we review the evolving story of the coronavirus endoribonuclease (EndoU). Coronavirus EndoU is encoded within the sequence of nonstructural protein (nsp) 15, which was initially identified as a component of the viral replication complex. Biochemical and structural studies revealed the enzymatic nature of nsp15/EndoU, which was postulated to be essential for the unique replication cycle of viruses in the order Nidovirales. However, the role of nsp15 in coronavirus replication was enigmatic as EndoU-deficient coronaviruses were viable and replicated to near wild-type virus levels in fibroblast cells. A breakthrough in our understanding of the role of EndoU was revealed in recent studies, which showed that EndoU mediates the evasion of viral double-stranded RNA recognition by host sensors in macrophages. This new discovery of nsp15/EndoU function leads to new opportunities for investigating how a viral EndoU contributes to pathogenesis and exploiting this enzyme for therapeutics and vaccine design against pathogenic coronaviruses.",,"['Deng, Xufang', 'Baker, Susan C']",,,,
,PMC,Combating intracellular pathogens with repurposed host-targeted drugs,http://dx.doi.org/10.1021/acsinfecdis.7b00268,PMC5807128,,,"There is a large, global unmet need for the development of countermeasures to combat intracellular pathogens. The development of novel antimicrobials is expensive, slow, and typically focuses on selective inhibition of proteins encoded by a single pathogen, thereby providing a narrow spectrum of coverage. The repurposing of approved drugs targeting host functions required for microbial infections represents a promising alternative. This review summarizes progress and challenges in the repurposing of approved drugs as host-targeted broad-spectrum agents for the treatment of intracellular pathogens. These strategies include targeting both cellular factors required for infection by various viruses, obligate intracellular bacteria, and/or protozoa as well as factors that modulate the host immune response to these microbial infections. The repurposed approach offers complementary means to develop therapeutics against existing and emerging intracellular microbial threats.",,"['Schor, Stanford', 'Einav, Shirit']",,,,
,PMC,Genotype 2 Strains of Porcine Reproductive and Respiratory Syndrome Virus Dysregulate Alveolar Macrophage Cytokine Production via the Unfolded Protein Response,http://dx.doi.org/10.1128/JVI.01251-17,PMC5752938,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) infects alveolar macrophages (AMϕ), causing dysregulated alpha interferon (IFN-α) and tumor necrosis factor alpha (TNF-α) production through a mechanism(s) yet to be resolved. Here, we show that AMϕ infected with PRRSV secreted a reduced quantity of IFN-α following exposure of the cell to synthetic double-stranded RNA (dsRNA). This reduction did not correlate with reduced IFNA1 gene transcription. Rather, it coincided with two events that occurred late during infection and that were indicative of translational attenuation, specifically, the activation of eukaryotic translation initiation factor 2α (eIF2α) and the appearance of stress granules. Notably, the typical rapid production of TNF-α by AMϕ exposed to lipopolysaccharide (LPS) was suppressed or enhanced by PRRSV, depending on when the LPS exposure occurred after virus infection. If exposure was delayed until 6 h postinfection (hpi) so that the development of the cytokine response coincided with the time in which phosphorylation of eIF2α by the stress sensor PERK (protein kinase RNA [PKR]-like ER kinase) occurred, inhibition of TNF-α production was observed. However, if LPS exposure occurred at 2 hpi, prior to a detectable onset of eIF2α phosphorylation, a synergistic response was observed due to the earlier NF-κB activation via the stress sensor IRE1α (inositol-requiring kinase 1α). These results suggest that the asynchronous actions of two branches of the unfolded protein response (UPR), namely, IRE1α, and PERK, activated by ER stress resulting from the virus infection, are associated with enhancement or suppression of TNF-α production, respectively. IMPORTANCE The activation of AMϕ is controlled by the microenvironment to deter excessive proinflammatory cytokine responses to microbes that could impair lung function. However, viral pneumonias frequently become complicated by secondary bacterial infections, triggering severe inflammation, lung dysfunction, and death. Although dysregulated cytokine production is considered an integral component of the exacerbated inflammatory response in viral-bacterial coinfections, the mechanism responsible for this event is unknown. Here, we show that PRRSV replication in porcine AMϕ triggers activation of the IRE1α branch of the UPR, which causes a synergistic TNF-α response to LPS exposure. Thus, the severe pneumonias typically observed in pigs afflicted with PRRSV-bacterial coinfections could result from dysregulated, overly robust TNF-α production in response to opportunistic pathogens that is not commensurate with the typical restrained reaction by uninfected AMϕ. This notion could help in the design of therapies to mitigate the severity of viral and bacterial coinfections.",,"['Chen, Wei-Yu', 'Schniztlein, William M.', 'Calzada-Nova, Gabriela', 'Zuckermann, Federico A.']",,,,
,PMC,"Comparison of 3 vaccination strategies against porcine reproductive and respiratory syndrome virus, Mycoplasma hyopneumoniae, and porcine circovirus type 2 on a 3 pathogen challenge model",,PMC5764041,,,"The objective of this study was to compare clinical, microbiologic, immunologic, and pathologic parameters in pigs each concurrently administered porcine reproductive and respiratory syndrome virus (PRRSV), Mycoplasma hyopneumoniae, and porcine circovirus type 2 (PCV2) vaccine from 1 of 2 commercial sources at 21 days of age and challenged with field strains of each of the 3 pathogens. Pigs were challenged with PRRSV and M. hyopneumoniae at 42 days of age (−14 days post-challenge, dpc) followed by a challenge with PCV2 at 56 days of age (0 dpc). Significant differences were observed between vaccinated challenged and unvaccinated challenged groups in clinical (average daily gain and clinical signs), microbiologic (viremia and nasal shedding), immunologic (antibodies and interferon-γ secreting cells), and pathologic (lesions) outcomes. Significant differences were observed among the 3 vaccinated challenged groups in microbiologic (nasal shedding of M. hyopneumoniae and viremia of PCV2) and immunologic (M. hyopneumoniae- and PCV2-specific interferon-γ secreting cells) outcomes. The vaccination regimen for PRRSV vaccine, M. hyopneumoniae vaccine, and PCV2 vaccine is efficacious for controlling triple challenge with PRRSV, M. hyopneumoniae, and PCV2 from weaning to finishing period.",,"['Jeong, Jiwoon', 'Kang, Ikjae', 'Kim, Seeun', 'Park, Kee Hwan', 'Park, Changhoon', 'Chae, Chanhee']",,,,
,PMC,Correlation between neonatal calf diarrhea and the level of maternally derived antibodies,,PMC5960765,,,"Passively acquired antibodies through colostrum will protect calves against etiological agents of neonatal calf diarrhea. Among them enteric diseases due to strains of Enterotoxigenic Escherichia coli (ETEC) are the most commonly occurring form of colibacillosis in newborn calves. Specific antibodies against whole ETEC cells and total immunoglobulin G in dam serum, colostrum and calf serum were determined. There were significant differences (P=0.0005) between antibody titers in normal and diarrheic groups, in which diarrheic group had a higher titer. Total IgG concentration in diarrheic calves (20.86 ± 0.49), their dams (23.48 ± 0.54) and colostrum (33.40 ± 0.50) was less than normal group (P=0.0005). There was a highly significant positive correlation between dam total IgG with calf total IgG (r=0.022; ratio=52.11). Colostral anti-E. coli antibody had a highly significant positive correlation with anti-E. coli in calf serum (r=0.345; ratio=0.62). Anti-E. coli antibody in calf serum had a highly significant negative correlati with total IgG of dam serum, colostrum and calf serum. While the level of anti-E. coli antibodies in diarrheic group was considerably higher than normal group, our findings reported here are in agreement that immunity to diarrhea also might be correlated with maternal cells or cellular components as well as cytokines which are transferred by colostrum to neonatal calves. Nevertheless, the level of maternally derived antibodies is a promising indicator for passive immunity and protection against diarrhea in neonatal calves.",,"['Al-Alo, K. Z. K.', 'Nikbakht Brujeni, Gh.', 'Lotfollahzadeh, S.', 'Moosakhani, F.', 'Gharabaghi, A.']",,,,
,PMC,Flammability of Respirators and other Head and Facial Personal Protective Equipment,,PMC6198820,,,"BACKGROUND: Personal protective equipment (PPE) is worn by workers in surgical settings to protect them and patients. Food and Drug Administration (FDA) clears some PPE (e.g., surgical masks (SM)) as class II medical devices, and regulates some (e.g. surgical head cover) as class I exempt devices. For respiratory protection, National Institute for Occupational Safety and Health (NIOSH)-approved N95 filtering facepiece respirators (FFRs), and powered air-purifying respirators (PAPRs) are used. One type of PPE, “surgical N95 respirators”, is a NIOSH-approved FFR that is also cleared by the FDA for use in medical settings. The surgical environment poses unique risks such as the potential for surgical fires. As part of its substantial equivalence determination process, FDA requests testing of flammability and other parameters for SM and surgical N95 respirators. A lack of data regarding flammability of PPE used in healthcare exists. We hypothesize that commonly used PPE, regardless of whether regulated and/or cleared by FDA or not, will pass an industry standard such as the 16 CFR 1610 flammability test. METHODS: Eleven N95 FFR models, eight surgical N95 respirator models, seven SM models, five surgical head cover models, and five PAPR hood models were evaluated for flammability with a 45 degree flammability tester using the 16 CFR 1610 method. Three common fabrics were included for comparison. RESULTS: All of the PPE samples regulated/and or cleared by FDA or not, passed the flammability test at class 1 (normal flammability), meaning they are less likely to burn. Only one of the three common fabrics, a cotton fabric at the lowest basis weight, was class 3 (high flammability). CONCLUSIONS: The results obtained in the study suggest that NIOSH-approved N95 FFRs would likely pass the 16 CFR 1610 flammability standard. Moreover, results suggest that NIOSH is capable of undertaking flammability testing using the 16 CFR 1610 standard as the flammability results NIOSH obtained for N95 FFRs were comparable to the results obtained by a third party independent laboratory.",,"['Rengasamy, Samy', 'Niezgoda, George', 'Shaffer, Ron']",,,,
,PMC,Cathepsin B plays a key role in optimal production of the influenza A virus,http://dx.doi.org/10.4172/2324-8955.1000178,PMC5770218,,,"BACKGROUND: Influenza A virus (IAV) is the etiologic agent of the febrile respiratory illness, commonly referred to as ‘flu’. The lysosomal protease cathepsin B (CTSB) has shown to be involved in the lifecycle of various viruses. Here, we examined the role of CTSB in the IAV lifecycle. METHODS: CTSB-deficient (CTSB(−/−)) macrophages and the human lung epithelial cell line A549 cells treated with CA-074Me were infected with the A/Puerto Rico/8/34 strain of IAV (IAV-PR8). Viral entry and propagation were measured through quantitative real-time RT-PCR; production and localization of hemagglutinin (HA) protein in the infected host cells were analysed by Western blots, flow cytometry and confocal microscopy; production of progeny viruses were measured by a hemagglutination assay. RESULTS: CTSB(−/−) macrophages and CA-074Me-treated A549 cells had no defects in incorporating IAV-PR8 virions and permitting viral RNA synthesis. However, these cells produced significantly lower amounts of HA protein and progeny virions than wild-type or untreated cells. CONCLUSION: These data indicate that CTSB is involved in the expression of IAV-PR8 HA protein and subsequent optimal production of IAV-PR8 progeny virions. Targeting CTSB can be a novel therapeutic strategy for treating IAV infection.",,"['Coleman, Macon D.', 'Ha, Soon-Duck', 'Haeryfar, S.M. Mansour', 'Barr, Stephen Dominic', 'Kim, Sung Ouk']",,,,
,PMC,Imaging Proteolytic Activities in Mouse Models of Cancer,http://dx.doi.org/10.1007/978-1-4939-7595-2_22,PMC6435259,,,"Proteases are “protein-cleaving” enzymes, which, in addition to their non-specific degrading function, also catalyze the highly specific and regulated process of proteolytic processing, thus regulating multiple biological functions. Alterations in proteolytic activity occur during pathological conditions such as cancer. One of the major deregulated classes of proteases in cancer is caspases, the proteolytic initiators and mediators of the apoptotic machinery. The ability to image apoptosis noninvasively in living cells and animal models of cancer can not only provide new insight into the biological basis of the disease but can also be used as a quantitative tool to screen and evaluate novel therapeutic strategies. Optical molecular imaging such as bioluminescence-based genetically engineered biosensors has been developed in our laboratory and exploited to study protease activity in animal models with a high signal to noise. Using the circularly permuted form of firefly luciferase, we have developed a reporter for Caspase 3/7, referred to as Caspase 3/7 GloSensor. Here, we discuss the use of the Caspase 3/7 GloSensor for imaging apoptotic activity in mouse xenografts and genetically engineered mouse models of cancer and present the potential of this powerful platform technology to image the proteolytic activity of numerous other proteases.",,"['Pal, Anupama', 'Rehemtulla, Alnawaz']",,,,
,PMC,Improvement in Cardiac Function With Enzyme Replacement Therapy in a Patient With Infantile-Onset Pompe Disease,http://dx.doi.org/10.31486/toj.18.0049,PMC6292475,,,"BACKGROUND: Pompe disease is a lysosomal storage disorder that results from an inborn error of metabolism involving abnormal glycogen storage. Infantile-onset Pompe disease is the most severe phenotype, and enzyme replacement therapy with alglucosidase alfa (Lumizyme) improves medical and functional outcomes in patients with infantile-onset Pompe disease. CASE REPORT: We report the case of a patient with infantile-onset Pompe disease who presented with severe hypertrophic cardiomyopathy, systolic and diastolic cardiac dysfunction, and hypotonia. She experienced significant improvement in cardiac systolic function while receiving enzyme replacement therapy. CONCLUSION: Typically, patients with infantile-onset Pompe disease and severe hypertrophic cardiomyopathy are not as responsive to enzyme replacement therapy as patients with mild or no hypertrophic cardiomyopathy. We demonstrated the efficacy of enzyme replacement therapy in a patient with severe hypertrophic cardiomyopathy.",,"['Niyazov, Dmitriy', 'Lara, Diego A.']",,,,
,PMC,OWL-NETS: Transforming OWL Representations for Improved Network Inference,,PMC5737627,,,"Our knowledge of the biological mechanisms underlying complex human disease is largely incomplete. While Semantic Web technologies, such as the Web Ontology Language (OWL), provide powerful techniques for representing existing knowledge, well-established OWL reasoners are unable to account for missing or uncertain knowledge. The application of inductive inference methods, like machine learning and network inference are vital for extending our current knowledge. Therefore, robust methods which facilitate inductive inference on rich OWL-encoded knowledge are needed. Here, we propose OWL-NETS (NEtwork Transformation for Statistical learning), a novel computational method that reversibly abstracts OWL-encoded biomedical knowledge into a network representation tailored for network inference. Using several examples built with the Open Biomedical Ontologies, we show that OWL-NETS can leverage existing ontology-based knowledge representations and network inference methods to generate novel, biologically-relevant hypotheses. Further, the lossless transformation of OWL-NETS allows for seamless integration of inferred edges back into the original knowledge base, extending its coverage and completeness.",,"['Callahan, Tiffany J.', 'Baumgartner, William A.', 'Bada, Michael', 'Stefanski, Adrianne L.', 'Tripodi, Ignacio', 'White, Elizabeth K.', 'Hunter, Lawrence E.']",,,,
,PMC,New Advances in CNS Immunity against Viral Infection,http://dx.doi.org/10.1016/j.coviro.2017.12.003,PMC5990251,,,"The central nervous system (CNS) is an immunologically specialized organ where restrictive barrier structures protect the parenchyma from inflammation and infection. This protection is important in preventing damage to non-renewable resident cell populations, such as neurons, responsible for functions ranging from executive to autonomic. Despite these barriers, the CNS can be infected through several entry portals, giving rise to meningitis and encephalitis. Following infection, resident cells recruit peripherally-derived immune cells to sites of viral infection. In this review, we discuss recent advances in immune recruitment and entry at barrier structures as well as current immunotherapeutic strategies for the treatment of persistent viral infections.",,"['Manglani, Monica', 'McGavern, Dorian B.']",,,,
,PMC,Elevated Serum Levels of IL-6 and CXCL9 in Autoimmune Retinopathy (AIR) Patients,http://dx.doi.org/10.1016/j.jneuroim.2017.12.014,PMC5801042,,,"Autoimmune retinopathy (AIR) is a rare immune-mediated retinopathy associated with circulating antiretinal antibodies (ARAs). Other prominent features of AIR include visual field deficits and photoreceptor dysfunction in the setting of progressive unexplained vision loss. The role of inflammation is poorly understood in AIR. Since cytokines play a central role in the initiation and development of inflammation, we evaluated the presence of proinflammatory cytokines and chemokines in AIR patient sera. We demonstrate that IL-6 and CXCL9 are both elevated in AIR patient sera. Moreover, the presence and concentration of these 2 molecules appear to correlate with AIR patient disease severity. This cytokine profile, IL-6 and CXCL9, has been described to participate in a variety of autoimmune and inflammatory diseases. Our study provides support for an activated inflammatory process in AIR and identifies possible mechanisms that can drive autoimmunity in this disease.",,"['Detrick, Barbara', 'Gangaputra, Sapna', 'Palsgrove, Doreen N', 'Heaney, Christopher D', 'Hooks, John J', 'Sen, H Nida']",,,,
,PMC,The neonatal anti-viral response fails to control measles virus spread in neurons despite interferon-gamma expression and a Th1-like cytokine profile,http://dx.doi.org/10.1016/j.jneuroim.2017.12.018,PMC6003673,,,"Neonates are highly susceptible to viral infections in the periphery, potentially due to deviant cytokine responses. Here, we investigated the role of interferon-gamma (IFNγ), a key antiviral the neonatal brain. We found that (i) IFNγ, which is critical for viral control and survival in adults, delays mortality in neonates, (ii) IFNγ limits infiltration of macrophages, neutrophils, and T cells in the neonatal brain, (iii) neonates and adults differentially express pathogen recognition receptors and Type I interferons in response to the infection, (iv) both neonates and adults express IFNγ and other Th1-related factors, but expression of many cytokines/chemokines and IFNγ-responsive genes is age-dependent, and (v) administration of IFNγ extends survival and reduces CD4 T cell infiltration in the neonatal brain. Our findings suggest age-dependent expression of cytokine/chemokine profiles in the brain and distinct dynamic interplays between lymphocyte populations and cytokines/chemokines in MV-infected neonates.",,"['Ganesan, Priya', 'Chandwani, Manisha N.', 'Creisher, Patrick S.', 'Bohn, Larissa', 'O’Donnell, Lauren A.']",,,,
,PMC,Role of enhanced receptor engagement in the evolution of a pandemic acute hemorrhagic conjunctivitis virus,http://dx.doi.org/10.1073/pnas.1713284115,PMC5777043,,,"Acute hemorrhagic conjunctivitis (AHC) is a painful, contagious eye disease, with millions of cases in the last decades. Coxsackievirus A24 (CV-A24) was not originally associated with human disease, but in 1970 a pathogenic “variant” (CV-A24v) emerged, which is now the main cause of AHC. Initially, this variant circulated only in Southeast Asia, but it later spread worldwide, accounting for numerous AHC outbreaks and two pandemics. While both CV-A24 variant and nonvariant strains still circulate in humans, only variant strains cause AHC for reasons that are yet unknown. Since receptors are important determinants of viral tropism, we set out to map the CV-A24 receptor repertoire and establish whether changes in receptor preference have led to the increased pathogenicity and rapid spread of CV-A24v. Here, we identify ICAM-1 as an essential receptor for both AHC-causing and non-AHC strains. We provide a high-resolution cryo-EM structure of a virus–ICAM-1 complex, which revealed critical ICAM-1–binding residues. These data could help identify a possible conserved mode of receptor engagement among ICAM-1–binding enteroviruses and rhinoviruses. Moreover, we identify a single capsid substitution that has been adopted by all pandemic CV-A24v strains and we reveal that this adaptation enhances the capacity of CV-A24v to bind sialic acid. Our data elucidate the CV-A24v receptor repertoire and point to a role of enhanced receptor engagement in the adaptation to the eye, possibly enabling pandemic spread.",,"['Baggen, Jim', 'Hurdiss, Daniel L.', 'Zocher, Georg', 'Mistry, Nitesh', 'Roberts, Richard W.', 'Slager, Jasper J.', 'Guo, Hongbo', 'van Vliet, Arno L. W.', 'Wahedi, Maryam', 'Benschop, Kimberley', 'Duizer, Erwin', 'de Haan, Cornelis A. M.', 'de Vries, Erik', 'Casasnovas, José M.', 'de Groot, Raoul J.', 'Arnberg, Niklas', 'Stehle, Thilo', 'Ranson, Neil A.', 'Thibaut, Hendrik Jan', 'van Kuppeveld, Frank J. M.']",,,,
,PMC,"Award Winners and Abstracts of the 31st Annual Symposium of The Protein Society, Montreal, Canada, July 24–27, 2017",http://dx.doi.org/10.1002/pro.3349,PMC5743843,,,,,,,,,
,PMC,Tuberculosis in the elderly: Why inflammation matters,http://dx.doi.org/10.1016/j.exger.2017.12.021,PMC5967410,,,"Growing old is associated with an increase in the basal inflammatory state of an individual and susceptibility to many diseases, including infectious diseases. Evidence is growing to support the concept that inflammation and disease susceptibility in the elderly is linked. Our studies focus on the infectious disease tuberculosis (TB), which is caused by Mycobacterium tuberculosis (M.tb), a pathogen that infects approximately one fourth of the world’s population. Aging is a major risk factor for developing TB, and inflammation has been strongly implicated. In this review we will discuss the relationship between inflammation in the lung and susceptibility to develop and succumb to TB in old age. Further understanding of the relationship between inflammation, age, and M.tb will lead to informed decisions about TB prevention and treatment strategies that are uniquely designed for the elderly.",,"['Piergallini, Tucker J', 'Turner, Joanne']",,,,
,PMC,Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA,http://dx.doi.org/10.1073/pnas.1718806115,PMC5777078,,,"Coronaviruses (CoVs) stand out among RNA viruses because of their unusually large genomes (∼30 kb) associated with low mutation rates. CoVs code for nsp14, a bifunctional enzyme carrying RNA cap guanine N7-methyltransferase (MTase) and 3′-5′ exoribonuclease (ExoN) activities. ExoN excises nucleotide mismatches at the RNA 3′-end in vitro, and its inactivation in vivo jeopardizes viral genetic stability. Here, we demonstrate for severe acute respiratory syndrome (SARS)-CoV an RNA synthesis and proofreading pathway through association of nsp14 with the low-fidelity nsp12 viral RNA polymerase. Through this pathway, the antiviral compound ribavirin 5′-monophosphate is significantly incorporated but also readily excised from RNA, which may explain its limited efficacy in vivo. The crystal structure at 3.38 Å resolution of SARS-CoV nsp14 in complex with its cofactor nsp10 adds to the uniqueness of CoVs among RNA viruses: The MTase domain presents a new fold that differs sharply from the canonical Rossmann fold.",,"['Ferron, François', 'Subissi, Lorenzo', 'Silveira De Morais, Ana Theresa', 'Le, Nhung Thi Tuyet', 'Sevajol, Marion', 'Gluais, Laure', 'Decroly, Etienne', 'Vonrhein, Clemens', 'Bricogne, Gérard', 'Canard, Bruno', 'Imbert, Isabelle']",,,,
,PMC,Murine norovirus inhibits B cell development in the bone marrow of STAT1-deficient mice,http://dx.doi.org/10.1016/j.virol.2017.12.013,PMC5801037,,,"Noroviruses are a leading cause of gastroenteritis in humans and it was recently revealed that noroviruses can infect B cells. We demonstrate that murine norovirus (MNV) infection can significantly impair B cell development in the bone marrow in a signal transducer and activator of transcription 1 (STAT1) dependent, but interferon signaling independent manner. We also show that MNV replication is more pronounced in the absence of STAT1 in ex vivo cultured B cells. Interestingly, using bone marrow transplantation studies, we found that impaired B cell development requires Stat1(−/−) hematopoietic cells and Stat1(−/−) stromal cells, and that the presence of wild-type hematopoietic or stromal cells was sufficient to restore normal development of Stat1(−/−) B cells. These results suggest that B cells normally restrain norovirus replication in a cell autonomous manner, and that wild-type STAT1 is required to protect B cell development during infection.",,"['Hsu, Charlie C.', 'Meeker, Stacey M.', 'Escobar, Sabine', 'Brabb, Thea L.', 'Paik, Jisun', 'Park, Heon', 'Iritani, Brian M.', 'Maggio-Price, Lillian']",,,,
,PMC,"Viral metagenomics, protein structure, and reverse genetics: key strategies for investigating coronaviruses",http://dx.doi.org/10.1016/j.virol.2017.12.009,PMC5869085,,,"Viral metagenomics, modeling of protein structure, and manipulation of viral genetics are key approaches that have laid the foundations of our understanding of coronavirus biology. In this review, we discuss the major advances each method has provided and discuss how future studies should leverage these strategies synergistically to answer novel questions.",,"['Johnson, Bryan A.', 'Graham, Rachel L.', 'Menachery, Vineet D.']",,,,
,PMC,Adaptive Evolution Influences the Infectious Dose of MERS-CoV Necessary to Achieve Severe Respiratory Disease,http://dx.doi.org/10.1016/j.virol.2017.12.006,PMC5869108,,,"We recently established a mouse model (288–330(+/+)) that developed acute respiratory disease resembling human pathology following infection with a high dose (5×10(6) PFU) of mouse-adapted MERS-CoV (icMERSma1). Although this high dose conferred fatal respiratory disease in mice, achieving similar pathology at lower viral doses may more closely reflect naturally acquired infections. Through continued adaptive evolution of icMERSma1 we generated a novel mouse-adapted MERS-CoV (maM35c4) capable of achieving severe respiratory disease at doses between 10(3)–10(5) PFU. Novel mutations were identified in the maM35c4 genome that may be responsible for eliciting etiologies of acute respiratory distress syndrome at 10–1000 fold lower viral doses. Importantly, comparative genetics of the two mouse-adapted MERS strains allowed us to identify specific mutations that remained fixed through an additional 20 cycles of adaptive evolution. Our data indicate that the extent of MERS-CoV adaptation determines the minimal infectious dose required to achieve severe respiratory disease.",,"['Douglas, Madeline G.', 'Kocher, Jacob F.', 'Scobey, Trevor', 'Baric, Ralph S.', 'Cockrell, Adam S.']",,,,
,PMC,Antiviral Response in the Nasopharynx Identifies Patients With Respiratory Virus Infection,http://dx.doi.org/10.1093/infdis/jix648,PMC5853594,,,"BACKGROUND: Despite the high burden of respiratory infection and the importance of early and accurate diagnosis, there is no simple diagnostic test to rule in viral infection as a cause of respiratory symptoms. METHODS: We performed RNA sequencing on human nasal epithelial cells following stimulation of the intracellular viral recognition receptor RIG-I. Next, we evaluated whether measuring identified host mRNAs and proteins from patient nasopharyngeal swabs could predict the presence of a respiratory virus in the sample. RESULTS: Our first study showed that a signature of 3 mRNAs, CXCL10, IFIT2, and OASL, predicted respiratory virus detection with an accuracy of 97% (95% confidence interval [CI], 0.9–1.0), and identified proteins correlating with virus detection. In a second study, elevated CXCL11 or CXCL10 protein levels identified samples containing respiratory viruses, including viruses not on the initial test panel. Overall area under the curve (AUC) values were: CXCL11 AUC = 0.901 (95% CI, 0.86–0.94); CXCL10 AUC = 0.85 (95% CI, 0.80–0.91). CONCLUSIONS: Host antiviral mRNAs and single host proteins detectable using nasopharyngeal swabs accurately predict the presence of viral infection. This approach holds promise for developing rapid, cost-effective tests to improve management of patients with respiratory illnesses.",,"['Landry, Marie L', 'Foxman, Ellen F']",,,,
,PMC,"Big Data in Public Health: Terminology, Machine Learning, and Privacy",http://dx.doi.org/10.1146/annurev-publhealth-040617-014208,PMC6394411,,,"The digital world is generating data at a staggering and still increasing rate. While these ‘Big Data’ have unlocked novel opportunities to understand public health, they hold still greater potential for research and practice. This review explores several key issues arising around big data. First, we propose a taxonomy of sources of big data in order to clarify terminology and identify threads common across some subtypes of big data. Next, we consider common public health research and practice uses for big data, including surveillance, hypothesis-generating research, and causal inference, while exploring the role that machine learning may play in each use. We then consider the ethical implications of the big data revolution with particular emphasis on maintaining appropriate care for privacy in a world in which technology is rapidly changing social norms regarding the need for (and even the meaning of) privacy. Finally, we make suggestions regarding structuring teams and training to succeed in working with big data in research and practice.",,"['Mooney, Stephen J', 'Pejaver, Vikas']",,,,
,PMC,Investigations into the efficacy of multi-component cocaine vaccines,http://dx.doi.org/10.1016/j.bmcl.2017.12.043,PMC6013332,,,"Although cocaine addiction remains a serious health and societal problem in the United States, no FDA-approved treatment has been developed. Vaccines offer an exciting strategy for the treatment of cocaine addiction; however, vaccine formulations need to be optimized to improve efficacy. Herein, we examine the effectiveness of a tricomponent cocaine vaccine, defined as having its hapten (GNE) and adjuvant (cytosine-guanine oligodeoxynucleotide 1826, CpG ODN 1826) covalently linked via the immunogenic protein ovalbumin (OVA). The tricomponent vaccine (GNE-OVA-CpG 1826) and a vaccine of analogous, individual components (GNE-OVA + CpG ODN) were found to similarly induce highly specific anticocaine antibody production in mice and block cocaine’s stimulant effects in hyperlocomotor testing.",,"['Kimishima, Atsushi', 'Olson, Margaret E.', 'Janda, Kim D.']",,,,
,PMC,TRAF molecules in inflammation and inflammatory diseases,http://dx.doi.org/10.1007/s40495-017-0117-y,PMC5839642,,,"PURPOSE OF REVIEW: This review presents an overview of the current knowledge of TRAF molecules in inflammation with an emphasis on available human evidence and direct in vivo evidence of mouse models that demonstrate the contribution of TRAF molecules in the pathogenesis of inflammatory diseases. RECENT FINDINGS: The tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family of cytoplasmic proteins was initially identified as signaling adaptors that bind directly to the intracellular domains of receptors of the TNF-R superfamily. It is now appreciated that TRAF molecules are widely employed in signaling by a variety of adaptive and innate immune receptors as well as cytokine receptors. TRAF-dependent signaling pathways typically lead to the activation of nuclear factor-κBs (NF-κBs), mitogen-activated protein kinases (MAPKs), or interferon-regulatory factors (IRFs). Most of these signaling pathways have been linked to inflammation, and therefore TRAF molecules were expected to regulate inflammation and inflammatory responses since their discovery in 1990s. However, direct in vivo evidence of TRAFs in inflammation and especially in inflammatory diseases had been lacking for many years, partly due to the difficulty imposed by early lethality of TRAF2(−/−), TRAF3(−/−), and TRAF6(−/−) mice. With the creation of conditional knockout and lineage-specific transgenic mice of different TRAF molecules, our understanding about TRAFs in inflammation and inflammatory responses has rapidly advanced during the past decade. SUMMARY: Increasing evidence indicates that TRAF molecules are versatile and indispensable regulators of inflammation and inflammatory responses and that aberrant expression or function of TRAFs contributes to the pathogenesis of inflammatory diseases.",,"['Lalani, Almin I.', 'Zhu, Sining', 'Gokhale, Samantha', 'Jin, Juan', 'Xie, Ping']",,,,
,PMC,Antiproliferative activity of novel isatinyl/indanyl nitrones (INs) as potential spin trapping agents of free radical intermediates,http://dx.doi.org/10.1039/c7md00537g,PMC6083742,,,"A series of ketonitrones derived from isatin and indanone (INs) were synthesized and evaluated for their antiproliferative activities against several human cancer cell lines. Then, the antioxidant properties of these substrates were measured by the DPPH test to report their biological activity in terms of their spin trapping action. In particular, one substrate has showed very high biological and scavenging activity, probably due to the strong correlation between its spin trapping activity and structure.",,"['Maiuolo, Loredana', 'Feriotto, Giordana', 'Algieri, Vincenzo', 'Nardi, Monica', 'Russo, Beatrice', 'Di Gioia, Maria Luisa', 'Furia, Emilia', 'Tallarida, Matteo Antonio', 'Mischiati, Carlo', 'De Nino, Antonio']",,,,
,PMC,Downregulated cytoplasmic polyadenylation element-binding protein-4 is associated with the carcinogenesis of head and neck squamous cell carcinoma,http://dx.doi.org/10.3892/ol.2017.7661,PMC5778832,,,"Cytoplasmic polyadenylation element-binding protein-4 (CPEB4) is involved in several biological processes that are associated with cancer progression. However, it remains unknown whether CPEB4 expression levels are associated with head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to explore the potential function of CPEB4 in HNSCC. The expression of CPEB4 was analyzed in HNSCC from six Gene Expression Omnibus (GEO) datasets. Immunohistochemical staining was conducted to examine CPEB4 protein levels in an HNSCC tissue microarray (TMA). According to the GEO dataset analyses, CPEB4 gene expression was downregulated in HNSCC compared with normal samples (P<0.05). Notably, a statistical difference was observed between different tumor grades (P<0.05). Furthermore, the methylation of the CPEB4 gene in HNSCC was significantly increased compared with that observed in normal samples (P<0.01). The outcome from the TMA demonstrated that CPEB4 protein expression in human HNSCC tumors was significantly decreased compared with normal samples (P<0.05). In addition, the expression of CPEB4 protein was negatively associated with histological grades of HNSCC (P<0.05). The results from the present study suggested that CPEB4 may function as a tumor suppressor gene in HNSCC, which identifies the potential value of CPEB4 in predicting prognosis of HNSCC. Hypermethylation of the CPEB4 gene may be responsible for the downregulation of CPEB4 expression in HNSCC and result in tumorigenesis.",,"['Zeng, Manli', 'Li, Fen', 'Wang, Lei', 'Chen, Chen', 'Huang, Xiaolin', 'Wu, Xingyu', 'She, Wensheng', 'Zhou, Lin', 'Tao, Zezhang']",,,,
,PMC,Defining pharmacological targets by analysis of virus-host protein interactions,http://dx.doi.org/10.1016/bs.apcsb.2017.11.001,PMC6322211,,,"Viruses are obligate parasites that depend on cellular factors for replication. Pharmacological inhibition of essential viral proteins, mostly enzymes, is an effective therapeutic alternative in the absence of effective vaccines. However, this strategy commonly encounters drug resistance mechanisms that allow these pathogens to evade control. Due to the dependency on host factors for viral replication, pharmacological disruption of the host-pathogen protein-protein interactions (PPIs) is an important therapeutic alternative to block viral replication. In this review we discuss salient aspects of PPIs implicated in viral replication and advances in the development of small-molecules that inhibit viral replication through antagonism of these interactions.",,"['Llano, Manuel', 'Peña-Hernandez, Mario A.']",,,,
,PMC,"The Epidemiology of Imported Acute Infectious Diseases in Zhejiang Province, China, 2011–2016: Analysis of Surveillance Data",http://dx.doi.org/10.4269/ajtmh.17-0284,PMC5930882,,,"To explore epidemiological characteristics of imported acute infectious diseases between 2011 and 2016 in Zhejiang province, China. Data of imported infectious diseases from 2011 to 2016 was collected from the China Information System for Disease Control and Prevention in Zhejiang province, and subsequently analyzed for epidemiological characteristics. A survey was conducted to investigate clinicians’ abilities to diagnose these diseases in Zhejiang province. From 2011 to 2016, 1,241 cases of imported acute infectious disease were reported in Zhejiang province, including 1,078 malaria cases, 156 dengue cases, three chikungunya fever cases and four Zika cases. Between 2011 and 2016, incidences of these diseases increased (P < 0.001). For malaria, male adults for labor export were the most affected group. Seasonal fluctuation was not obvious. Plasmodium falciparum was the main malaria type (822 cases) and most cases were acquired from African Region (791/822, 96.1%). Plasmodium vivax cases (194 cases) were mainly from African Region (78/194, 40.2%) and South-East Asia Region (51/194, 26.3%). Meanwhile, for dengue, adults and tourists were the most affected groups. The incidence of dengue was particularly high in August and October. The percent of correct clinician responses in the survey of diagnosis knowledge was 54.6% (standard deviation = 21.0%); this percentage was particularly low in general practitioners and clinicians from township hospitals. The capabilities of clinicians to diagnose these diseases were low and should be improved. Efforts should be made in improving and disseminating proper preventive measures of high-risk populations, surveillance of imported cases, and prevention and control of local epidemics.",,"['Ding, Zheyuan', 'Wu, Chen', 'Wu, Haocheng', 'Lu, Qinbao', 'Lin, Junfen']",,,,
,PMC,Proportionality in Public Health Regulation: The Case of Dietary Supplements,http://dx.doi.org/10.1007/s41055-017-0023-3,PMC6430238,,,"The idea that the degree of infringement public health interventions have on individual rights should be proportional to the degree of expected benefits has emerged as an influential principle in public health ethics and policy. While proportionality makes sense in theory, it may be difficult to implement in practice, due to the inherent conflict between individual rights and the common good underlying the principle. To apply the proportionality principle to a decision of policy, one must still find a reasonable way of balancing these competing values in light of the available options and empirical evidence. In this article, I consider how the proportionality principle applies to the regulation of dietary supplements and examine some critiques of the current oversight system. I argue that it may be difficult maintain proportional oversight because the risks of dietary supplements vary considerably. Strengthening the regulations may therefore promote an appropriate level of regulation in some cases but lead to overregulation in others.",,"Resnik, David B.",,,,
,PMC,Malaria in Children,http://dx.doi.org/10.1016/j.idc.2017.10.008,PMC6051527,,,,,"['Kafai, Natasha M.', 'John, Audrey R. Odom']",,,,
,PMC,"Pediatric Community-Acquired Pneumonia in the United States: Changing Epidemiology, Diagnostic and Therapeutic Challenges, and Areas for Future Research",http://dx.doi.org/10.1016/j.idc.2017.11.002,PMC5801082,,,,,"['Katz, Sophie E.', 'Williams, Derek J.']",,,,
,PMC,Genetic characterization of bovine respiratory syncytial virus strains isolated in Italy: evidence for the circulation of new divergent clades,http://dx.doi.org/10.1177/1040638717746202,PMC6505857,,,"Bovine respiratory syncytial virus (BRSV) is circulating in cattle in Europe. Although vaccination helps control the disease, its prevalence within and among herds remains high. Previous genetic characterization studies revealed a strict geographic correlation between viral variants; on the other hand, they showed the emergence of new variants in northern Europe. Few studies have described BRSV distribution, and little is known about the genetic features of BRSV strains circulating in Italy. We studied sample-positive tests for BRSV, and sequenced the coding regions of the G and N proteins to determine the presence of divergent variants. Two different sets of sequences were found, including in samples from animals from vaccinated herds. The 2 groups of sequences correspond to 2 time periods and suggest an active role of herd immunity in preventing the spread of infection. Our findings that different strains of BRSV are circulating in Italy and that the virus is evolving rapidly highlight the importance of updating vaccination strategies.",,"['Bertolotti, Luigi', 'Giammarioli, Monica', 'Rosati, Sergio']",,,,
,PMC,Rapid Pathogen Identification in Bacterial Pneumonia Using Real-Time Metagenomics,http://dx.doi.org/10.1164/rccm.201703-0537LE,PMC5754443,,,,,"['Pendleton, Kathryn M.', 'Erb-Downward, John R.', 'Bao, Yuwei', 'Branton, William R.', 'Falkowski, Nicole R.', 'Newton, Duane W.', 'Huffnagle, Gary B.', 'Dickson, Robert P.']",,,,
,PMC,Curcumin combined with glycyrrhetinic acid inhibits the development of hepatocellular carcinoma cells by down-regulating the PTEN/PI3K/AKT signalling pathway,,PMC5752906,,,"Curcumin is an active component of turmeric, which is derived from the rhizomes of Curcuma longa. Glycyrrhetinic acid (GA) is a natural compound extracted from liquorice. Both curcumin and GA are widely used as anticancer agents for treating many human cancers. In this study, curcumin and GA were used separately and in combination to treat human hepatocellular carcinoma (HCC) HepG2 cells. MTT assays were used to evaluate cell proliferation. Flow cytometry was carried out to measure cell apoptosis and determine cell cycle progression. Western blot analyses were applied to determine the expression levels of B-cell lymphoma-2 (Bcl-2), B-cell associated X protein (Bax), phosphatase and tensin homolog (PTEN), phosphorylated phosphoinositide 3-kinase (PI3K) and AKT serine/threonine kinase 1 (Akt). The results showed that combined treatment with curcumin and GA resulted in a significant reduction in proliferation and an increase in apoptosis and G1 cell cycle arrest in HepG-2 cells. A xenograft tumour model showed that curcumin and GA suppressed HCC development in vivo. Moreover, by knocking down the expression of PTEN, we confirmed that curcumin and GA exert their anticancer effects by inhibiting the PTEN/PI3K/Akt signalling pathway. Collectively, these results indicate that the combination of curcumin and GA could effectively inhibit the development of HepG2 cells by inhibiting PTEN/PI3K/Akt signalling and could be a promising treatment strategy for patients with HCC.",,"['Chang, Mingxiang', 'Wu, Meimei', 'Li, Hanmin']",,,,
,PMC,"Nonhuman Primates and Translational Research: Progress, Opportunities, and Challenges",http://dx.doi.org/10.1093/ilar/ilx033,PMC5886318,,,"Nonhuman primates (NHPs) are the closest animal models to humans regarding genetics, physiology and behavior. Therefore, NHPs are usually a critical component in translational research projects aimed at developing therapeutics, vaccines, devices or other interventions aimed at preventing, curing or ameliorating human disease. NHPs are often used in conjunction with other animal models, such as rodents, and results obtained using NHPs must often be used as the final criterion for establishing the potential efficacy of a pharmaceutical or vaccine before transition to human clinical trails. In some cases, NHPs may be the only relevant animal models for a particlular translational study. This issue of the ILAR journal brings together, in one place, articles that discuss the use of NHP models for studying human diseases that are highly prevalent and that cause extraordinary human suffering and financial and social burdens. Topics covered in detail include: tuberculosis; viral hepatitis; HIV/AIDS; neurodegenerative disorders; Substance abuse disorders; vision and prevention of blindness; disorder associated with psychosocial processes, such as anxiety, depression and loneliness; cardiovascular disease; metabolic disease, such as obesity and metabolic syndrome; respiratory disease; and female reproduction, prenatal development and women's health. Proper husbandry of NHPs that reduces stress and maintains animal health is critical for the development of NHP models. This issue of the journal includes a review of procedures for environmental enrichment, which helps assure animal health and wellbeing. Taken together, these articles provide detailed reviews of the use of NHP models for translational investigations and discuss successes, limitations, challenges and opportunities associated with this research.",,"Harding, John D",,,,
,PMC,Murine Hepatitis Virus nsp14 Exoribonuclease Activity Is Required for Resistance to Innate Immunity,http://dx.doi.org/10.1128/JVI.01531-17,PMC5730787,,,"Coronaviruses (CoVs) are positive-sense RNA viruses that infect numerous mammalian and avian species and are capable of causing severe and lethal disease in humans. CoVs encode several innate immune antagonists that counteract the host innate immune response to facilitate efficient viral replication. CoV nonstructural protein 14 (nsp14) encodes 3′-to-5′ exoribonuclease activity (ExoN), which performs a proofreading function and is required for high-fidelity replication. Outside of the order Nidovirales, arenaviruses are the only RNA viruses that encode an ExoN, which functions to degrade double-stranded RNA (dsRNA) replication intermediates. In this study, we tested the hypothesis that CoV ExoN also functions to antagonize the innate immune response. We demonstrate that viruses lacking ExoN activity [ExoN(−)] are sensitive to cellular pretreatment with interferon beta (IFN-β) in a dose-dependent manner. In addition, ExoN(−) virus replication was attenuated in wild-type bone marrow-derived macrophages (BMMs) and partially restored in interferon alpha/beta receptor-deficient (IFNAR(−/−)) BMMs. ExoN(−) virus replication did not result in IFN-β gene expression, and in the presence of an IFN-β-mediated antiviral state, ExoN(−) viral RNA levels were not substantially reduced relative to those of untreated samples. However, ExoN(−) virus generated from IFN-β-pretreated cells had reduced specific infectivity and decreased relative fitness, suggesting that ExoN(−) virus generated during an antiviral state is less viable to establish a subsequent infection. Overall, our data suggest murine hepatitis virus (MHV) ExoN activity is required for resistance to the innate immune response, and antiviral mechanisms affecting the viral RNA sequence and/or an RNA modification act on viruses lacking ExoN activity. IMPORTANCE CoVs encode multiple antagonists that prevent or disrupt an efficient innate immune response. Additionally, no specific antiviral therapies or vaccines currently exist for human CoV infections. Therefore, the study of CoV innate immune antagonists is essential for understanding how CoVs overcome host defenses and to maximize potential therapeutic interventions. Here, we sought to determine the contributions of nsp14 ExoN activity in the induction of and resistance to the innate immune response. We show that viruses lacking nsp14 ExoN activity are more sensitive than wild-type MHV to restriction by exogenous IFN-β and that viruses produced in the presence of an antiviral state are less capable of establishing a subsequent viral infection. Our results support the hypothesis that murine hepatitis virus ExoN activity is required for resistance to the innate immune response.",,"['Case, James Brett', 'Li, Yize', 'Elliott, Ruth', 'Lu, Xiaotao', 'Graepel, Kevin W.', 'Sexton, Nicole R.', 'Smith, Everett Clinton', 'Weiss, Susan R.', 'Denison, Mark R.']",,,,
,PMC,The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae,http://dx.doi.org/10.1128/JVI.01558-17,PMC5730780,,,"Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales. Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection. HRTV delivers its genome into the cytoplasm by fusion of the viral envelope and endosomal membranes under low-pH conditions. Here, we describe the crystal structure of HRTV Gc in its postfusion conformation. The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family. However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation. This suggests their family-specific subunit arrangement during the fusogenic process and supports the recent taxonomic revision of bunyaviruses. Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens. IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans. It belongs to the newly defined family Phenuiviridae, order Bunyavirales. HRTV contains three single-stranded RNA segments (L, M, and S). The M segment of the virus encodes a polyprotein precursor that is cleaved into two glycoproteins, Gn and Gc. Gc is a fusion protein facilitating virus entry into host cells. Here, we report the crystal structure of the HRTV Gc protein. The structure displays a typical class II fusion protein conformation. Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses. Our results expand the knowledge of bunyavirus fusion proteins and help us to understand bunyavirus characterizations. This study provides useful information to improve protection against and therapies for bunyavirus infections.",,"['Zhu, Yaohua', 'Wu, Yan', 'Chai, Yan', 'Qi, Jianxun', 'Peng, Ruchao', 'Feng, Wen-Hai', 'Gao, George Fu']",,,,
,PMC,Perinatal nutrition interacts with genetic background to alter behavior in a parent-of-origin-dependent manner in adult Collaborative Cross mice,http://dx.doi.org/10.1111/gbb.12438,PMC6705147,,,"Previous studies in animal models and humans have shown that exposure to nutritional deficiencies in the perinatal period increases the risk of psychiatric disease. Less well understood is how such effects are modulated by the combination of genetic background and parent-of-origin (PO). To explore this, we exposed female mice from 20 Collaborative Cross (CC) strains to protein deficient, vitamin D deficient, methyl donor enriched or standard diet during the perinatal period. These CC females were then crossed to a male from a different CC strain to produce reciprocal F1 hybrid females comprising 10 distinct genetic backgrounds. The adult F1 females were then tested in the open field, light/dark, stress-induced hyperthermia, forced swim and restraint stress assays. Our experimental design allowed us to estimate effects of genetic background, perinatal diet, PO and their interactions on behavior. Genetic background significantly affected all assessed phenotypes. Perinatal diet exposure interacted with genetic background to affect body weight, basal body temperature, anxiety-like behavior and stress response. In 8 of 9 genetic backgrounds, PO effects were observed on multiple phenotypes. Additionally, we identified a small number of diet-by-PO effects on body weight, stress response, anxiety- and depressive-like behavior. Our data show that rodent behaviors that model psychiatric disorders are affected by genetic background, PO and perinatal diet, as well as interactions among these factors.",,"['Schoenrock, S. A.', 'Oreper, D.', 'Farrington, J.', 'McMullan, R. C.', 'Ervin, R.', 'Miller, D. R.', 'Pardo-Manuel de Villena, F.', 'Valdar, W.', 'Tarantino, L. M.']",,,,
,PMC,Portable platform for rapid in-field identification of human fecal pollution in water,http://dx.doi.org/10.1016/j.watres.2017.12.023,PMC5999531,,,"Human fecal contamination of water is a public health risk. However, inadequate testing solutions frustrate timely, actionable monitoring. Bacterial culture-based methods are simple but typically cannot distinguish fecal host source. PCR assays can identify host sources but require expertise and infrastructure. To bridge this gap we have developed a field-ready nucleic acid diagnostic platform and rapid sample preparation methods that enable on-site identification of human fecal contamination within 80 min of sampling. Our platform relies on loop-mediated isothermal amplification (LAMP) of human-associated Bacteroides HF183 genetic markers from crude samples. Oligonucleotide strand exchange (OSD) probes reduce false positives by sequence specifically transducing LAMP amplicons into visible fluorescence that can be photographed by unmodified smartphones. Our assay can detect as few as 17 copies/ml of human-associated HF183 targets in sewage-contaminated water without cross-reaction with canine or feline feces. It performs robustly with a variety of environmental water sources and with raw sewage. We have also developed lyophilized assays and inexpensive 3D-printed devices to minimize cost and facilitate field application.",,"['Jiang, Yu Sherry', 'Riedel, Timothy E.', 'Popoola, Jessica A.', 'Morrow, Barrett R.', 'Cai, Sheng', 'Ellington, Andrew D.', 'Bhadra, Sanchita']",,,,
,PMC,Efficacy of H120 and Ma5 avian infectious bronchitis vaccines in early challenge against QX strain,http://dx.doi.org/10.1007/s13337-017-0414-4,PMC5877842,,,"Infectious bronchitis (IB) is a highly infectious avian pathogen, which affects the respiratory tract, gut, reproductive system, and kidney of chicks of all ages. Many different serotypes of IB virus (IBV) are recognized which cause different clinical manifestations. According to the antigenic differences, different serotypes of the virus do not cross-protect. Massachusetts serotype induces the best cross-protection against other serotypes. Recently, the IBV QX strain has been detected in Iran. QX strain causes permanent damage to the oviduct if it occurs in the early life cycle and is a significant factor in layer and breeder chicken flocks. In this study, we compare the H120 and Ma5 vaccines’ protection against early challenge with the QX strain in commercial chicks. one-day-old commercial chicks were divided into six groups. Groups 1 and 2 were unvaccinated groups. Groups 3 and 5 were vaccinated with the H120 vaccine (eye drop) and groups 4 and 6 were vaccinated with Ma5 (eye drop) on the 6th day (5 days after vaccination). Groups 2, 3 and 4 challenged (oculonasal) with QX strain (10^(4) EID50). Ciliostasis test, histopathology, and quantitative real-time RT-PCR were done at 11 days-old of age. Results showed that neither H120 nor Ma5 could induce proper cross-protection against QX early challenge, but the viral load and adverse pathological records in vaccinated chicks were less than that in the non-vaccinated groups. It can be concluded that vaccination on the first day of the life of a chick offers not full protection against the IBV QX strain but reduced the viral load and pathological damages in vaccinated chickens. Applying other forms of vaccination and using different genotypes on one-day-old chicks are suggested.",,"['Karimi, Vahid', 'Ghalyanchilangeroudi, Arash', 'Hashemzadeh, Masoud', 'Rahimi, Forough', 'Zabihi Petroudi, Mohammad Taha', 'Farahani, Reza KH', 'Maghsoudloo, Hossein', 'Abdollahi, Hamed']",,,,
,PMC,Diagnostic and prognostic plasma biomarkers for idiopathic pneumonia syndrome after hematopoietic cell transplantation,http://dx.doi.org/10.1016/j.bbmt.2017.11.039,PMC5902640,,,"Idiopathic pneumonia syndrome (IPS) is a non-infectious pulmonary complication after hematopoietic cell transplantation (HCT) and is difficult to diagnose. We evaluated six candidate proteins in plasma samples at day 7 after HCT and at onset of IPS from 41 IPS cases to identify potential IPS diagnostic or prognostic biomarkers. Samples at similar times from 162 HCT recipients without documented infections and 37 HCT recipients with respiratory viral pneumonia served as controls. In multivariable models, a combination of Stimulation-2 (ST2, OR 2.8; p<0.001) and Interleukin-6 (IL-6, OR 1.4; p=0.025) was the best panel to distinguish IPS at diagnosis from unaffected controls, while tumor necrosis factor receptor 1 (TNFR1, OR 2.9; p=0.002) was the best marker when comparing patients with IPS and viral pneumonia. The area under the curve of the receiver operating characteristic (ROC) curves for discriminating between IPS and unaffected controls at day 7 post-HCT were 0.8 for ST2, 0.75 for IL-6, and 0.68 for TNFR1. Using estimated sensitivity and specificity values from cutoffs determined with the ROC analysis (cutoff level: ST2, 21 ng/mL; IL-6, 61 pg/mL; TNFR1 3421 pg/mL), we calculated positive predictive values (PPV) for a range of estimated population prevalence values of IPS. Among the three markers, ST2 showed the highest PPV for IPS occurrence. Based on an 8% assumed prevalence, a positive ST2 test increased likelihood of IPS to 50%. We conclude that a prospective validation study is warranted to determine whether a plasma biomarker panel can help with the non-invasive diagnosis and prognosis of IPS.",,"['Seo, Sachiko', 'Yu, Jeffrey', 'Jenkins, Isaac C', 'Leisenring, Wendy M', 'Steven-Ayers, Terry', 'Kuypers, Jane M', 'Huang, Meei-Li', 'Jerome, Keith R', 'Boeckh, Michael', 'Paczesny, Sophie']",,,,
,PMC,"Nonhuman Primate Models of Respiratory Disease: Past, Present, and Future",http://dx.doi.org/10.1093/ilar/ilx030,PMC5886323,,,"The respiratory system consists of an integrated network of organs and structures that primarily function for gas exchange. In mammals, oxygen and carbon dioxide are transmitted through a complex respiratory tract, consisting of the nasal passages, pharynx, larynx, and lung. Exposure to ambient air throughout the lifespan imposes vulnerability of the respiratory system to environmental challenges that can contribute toward development of disease. The importance of the respiratory system to human health is supported by statistics from the Centers for Disease Control and Prevention; in 2015, chronic lower respiratory diseases were the third leading cause of death in the United States. In light of the significant mortality associated with respiratory conditions that afflict all ages of the human population, this review will focus on basic and preclinical research conducted in nonhuman primate models of respiratory disease. In comparison with other laboratory animals, the nonhuman primate lung most closely resembles the human lung in structure, physiology, and mucosal immune mechanisms. Studies defining the influence of inhaled microbes, pollutants, or allergens on the nonhuman primate lung have provided insight on disease pathogenesis, with the potential for elucidation of molecular targets leading to new treatment modalities. Vaccine trials in nonhuman primates have been crucial for confirmation of safety and protective efficacy against infectious diseases of the lung in a laboratory animal model that recapitulates pathology observed in humans. In looking to the future, nonhuman primate models of respiratory diseases will continue to be instrumental for translating biomedical research for improvement of human health.",,"['Miller, Lisa A', 'Royer, Christopher M', 'Pinkerton, Kent E', 'Schelegle, Edward S']",,,,
,PMC,"Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials",http://dx.doi.org/10.1016/S0140-6736(17)33105-7,PMC6379903,,,"BACKGROUND: The Zika virus epidemic and associated congenital infections have prompted rapid vaccine development. We assessed two new DNA vaccines expressing premembrane and envelope Zika virus structural proteins. METHODS: We did two phase 1, randomised, open-label trials involving healthy adult volunteers. The VRC 319 trial, done in three centres, assessed plasmid VRC5288 (Zika virus and Japanese encephalitis virus chimera), and the VRC 320, done in one centre, assessed plasmid VRC5283 (wild-type Zika virus). Eligible participants were aged 18–35 years in VRC19 and 18–50 years in VRC 320. Participants were randomly assigned 1:1 by a computer-generated randomisation schedule prepared by the study statistician. All participants received intramuscular injection of 4 mg vaccine. In VRC 319 participants were assigned to receive vaccinations via needle and syringe at 0 and 8 weeks, 0 and 12 weeks, 0, 4, and 8 weeks, or 0, 4, and 20 weeks. In VRC 320 participants were assigned to receive vaccinations at 0, 4, and 8 weeks via single-dose needle and syringe injection in one deltoid or split-dose needle and syringe or needle-free injection with the Stratis device (Pharmajet, Golden, CO, USA) in each deltoid. Both trials followed up volunteers for 24 months for the primary endpoint of safety, assessed as local and systemic reactogenicity in the 7 days after each vaccination and all adverse events in the 28 days after each vaccination. The secondary endpoint in both trials was immunogenicity 4 weeks after last vaccination. These trials are registered with ClinicalTrials.gov, numbers NCT02840487 and NCT02996461. FINDINGS: VRC 319 enrolled 80 participants (20 in each group), and VRC 320 enrolled 45 participants (15 in each group). One participant in VRC 319 and two in VRC 320 withdrew after one dose of vaccine, but were included in the safety analyses. Both vaccines were safe and well tolerated. All local and systemic symptoms were mild to moderate. In both studies, pain and tenderness at the injection site was the most frequent local symptoms (37 [46%] of 80 participants in VRC 319 and 36 [80%] of 45 in VRC 320) and malaise and headache were the most frequent systemic symptoms (22 [27%] and 18 [22%], respectively, in VRC 319 and 17 [38%] and 15 [33%], respectively, in VRC 320). For VRC5283, 14 of 14 (100%) participants who received split-dose vaccinations by needle-free injection had detectable positive antibody responses, and the geometric mean titre of 304 was the highest across all groups in both trials. INTERPRETATION: VRC5283 was well tolerated and has advanced to phase 2 efficacy testing.",,"['Gaudinski, Martin R', 'Houser, Katherine V', 'Morabito, Kaitlyn M', 'Hu, Zonghui', 'Yamshchikov, Galina', 'Rothwell, Ro Shauna', 'Berkowitz, Nina', 'Mendoza, Floreliz', 'Saunders, Jamie G', 'Novik, Laura', 'Hendel, Cynthia S', 'Holman, LaSonji A', 'Gordon, Ingelise J', 'Cox, Josephine H', 'Edupuganti, Srilatha', 'McArthur, Monica A', 'Rouphael, Nadine G', 'Lyke, Kirsten E', 'Cummings, Ginny E', 'Sitar, Sandra', 'Bailer, Robert T', 'Foreman, Bryant M', 'Burgomaster, Katherine', 'Pelc, Rebecca S', 'Gordon, David N', 'DeMaso, Christina R', 'Dowd, Kimberly A', 'Laurencot, Carolyn', 'Schwartz, Richard M', 'Mascola, John R', 'Graham, Barney S', 'Pierson, Theodore C', 'Ledgerwood, Julie E', 'Chen, Grace L', None]",,,,
,PMC,The essential role of mitochondrial dynamics in antiviral immunity,http://dx.doi.org/10.1016/j.mito.2017.11.007,PMC5988924,,,"Viruses alter cellular physiology and function to establish cellular environment conducive for viral proliferation. Viral immune evasion is an essential aspect of viral persistence and proliferation. The multifaceted mitochondria play a central role in many cellular events such as metabolism, bioenergetics, cell death, and innate immune signaling. Recent findings accentuate that viruses regulate mitochondrial function and dynamics to facilitate viral proliferation. In this review, we will discuss how viruses exploit mitochondrial dynamics to modulate mitochondria-mediated antiviral innate immune response during infection. This review will provide new insight to understanding the virus-mediated alteration of mitochondrial dynamics and functions to perturb host antiviral immune signaling.",,"['Kim, Seong-Jun', 'Ahn, Dae-Gyun', 'Syed, Gulam H.', 'Siddiqui, Aleem']",,,,
,PMC,The RNA-binding site of poliovirus 3C protein doubles as a phosphoinositide-binding domain,http://dx.doi.org/10.1016/j.str.2017.11.001,PMC5728361,,,"Some viruses use phosphatidylinositol phosphate (PIP) to mark membranes used for genome replication or virion assembly. PIP-binding motifs of cellular proteins do not exist in viral proteins. Molecular-docking simulations revealed a putative site of PIP binding to poliovirus (PV) 3C protein that was validated using NMR spectroscopy. The PIP-binding site was located on a highly dynamic α-helix that also functions in RNA binding. Broad PIP-binding activity was observed in solution using a fluorescence polarization assay or in the context of a lipid bilayer using an on-chip, fluorescence assay. All-atom molecular dynamics simulations of the 3C protein-membrane interface revealed PIP clustering and perhaps PIP-dependent conformations. PIP clustering was mediated by interaction with residues that interact with the RNA phosphodiester backbone. We conclude that 3C binding to membranes will be determined by PIP abundance. We suggest that the duality of function observed for 3C may extend to RNA-binding proteins of other viruses.",,"['Shengjuler, Djoshkun', 'Chan, Yan Mei', 'Sun, Simou', 'Moustafa, Ibrahim M.', 'Li, Zhen-Lu', 'Gohara, David W.', 'Buck, Matthias', 'Cremer, Paul S.', 'Boehr, David D.', 'Cameron, Craig E.']",,,,
,PMC,Determination of the diversity of astroviruses in feces from cats in Florida,http://dx.doi.org/10.1177/1040638717747322,PMC6505883,,,"Astroviruses are small, nonenveloped RNA viruses that have been linked to numerous diseases in a variety of species, including enteric disease in humans and cheetahs. Species Mamastrovirus 2, previously known as feline astrovirus, has been isolated from the feces of domestic cats and cheetahs. A total of 122 cat fecal samples from Alachua County, FL Animal Services and the Veterinary Community Outreach Program at the University of Florida were analyzed, and 35 contained astroviral RNA that was amplified and identified using consensus RT-PCR and sequence analysis. Using phylogenetic analysis, 19 of the astroviral sequences were identified as Mamastrovirus 2, making it the most prevalent astrovirus in this population. Three samples were identified as an astrovirus similar to viruses previously identified in foxes in The Netherlands and a cat in California, and one was similar to a bat astrovirus. One astroviral sequence was identified as an Avastrovirus. Although a causative relationship between mamastroviruses and enteric disease in cats has yet to be established, it is clear that mamastroviruses are prevalent, and an understanding of prevalence of astroviral types may help direct future test development.",,"['Lawler, Patricia E.', 'Cook, Kirstin A.', 'Williams, Hannah G.', 'Archer, Linda L.', 'Schaedel, Karen E.', 'Isaza, Natalie M.', 'Wellehan, James F. X.']",,,,
,PMC,Second International Conference on Crimean-Congo Hemorrhagic Fever,http://dx.doi.org/10.1016/j.antiviral.2017.11.019,PMC6497152,,,"The Second International Conference on Crimean-Congo Hemorrhagic Fever (CCHF) was held in Thessaloniki, Greece, from September 10–13, 2017, and brought together international public health professionals, clinicians, ecologists, and basic laboratory researchers. Nearly 100 participants, representing 24 countries and the World Health Organization (WHO), were in attendance. Meeting sessions covered the epidemiology of CCHF in humans; ticks and virus-tick interactions; wild and domestic animal hosts; molecular virology; taxonomic classification; pathogenesis and animal models; clinical aspects and diagnosis; clinical management and clinical trials; and disease prevention in humans. The concluding session focused on recent WHO recommendations for public health measures and future research. This report summarizes lectures by the invited speakers and highlights advances in the field",,"['Spengler, Jessica R.', 'Bente, Dennis A.', 'Bray, Mike', 'Burt, Felicity', 'Hewson, Roger', 'Korukluoglu, Gülay', 'Mirazimi, Ali', 'Weber, Friedemann', 'Papa, Anna']",,,,
,PMC,Evaluating interest in an influenza A(H5N1) vaccine among laboratory workers who work with highly-pathogenic avian influenza viruses in the United States,http://dx.doi.org/10.1016/j.vaccine.2017.10.104,PMC5759037,,,"BACKGROUND: Highly pathogenic avian influenza A (HPAI) viruses found in poultry and wild birds occasionally infect humans and can cause serious disease. In 2014, the Advisory Committee on Immunization Practices (ACIP) reviewed data from one licensed ASO3-adjuvanted influenza A(H5N1) vaccine for consideration of use during inter-pandemic periods among persons with occupational exposure. To guide vaccine policy decisions, we conducted a survey of laboratory workers to assess demand for HPAI vaccination. METHODS: We designed an anonymous web survey (EpiInfo 7.0) to collect information on demographics, type of work and time spent with HPAI viruses, and interest in HPAI vaccination. Eligible participants were identified from 42 entities registered with United States Department of Agriculture’s Agricultural Select Agent program in 2016 and emailed electronic surveys. Personnel with Biosafety Level 3 enhanced (BSL-3E) laboratory access were surveyed. Descriptive analysis was performed. RESULTS: Overall, 131 responses were received from 33 principal investigators, 26 research scientists, 24 technicians, 15 postdoctoral fellows, 6 students, and 27 others. The estimated response rate was 15% among the laboratory personnel of responding principal investigators. One hundred respondents reported working in a BSL-3E area where HPAI experiments occurred with a mean time of 5.1–11.7 h per week. Overall, 49% were interested in receiving an A(H5N1) vaccine. By role, interest was highest among students (80%) and among those who spent >50% of their time in a BSL-3E area (64%). Most (61%) of those who said they might be or were not interested in vaccine believed it would not provide additional protection to current safety practices. CONCLUSIONS: Half of responding laboratory workers was interested in receiving an influenza A(H5N1) vaccine. HPAI vaccination of laboratory workers at risk of occupational exposure could be used along with existing safety practices to protect this population.",,"['Russell, Kate E.', 'Bresee, J.S.', 'Katz, J.M.', 'Olsen, S.J.']",,,,
,PMC,Public Health Planning for Pets,http://dx.doi.org/10.2105/AJPH.2017.304114,PMC5678400,,,,,"Rothstein, Mark A.",,,,
,PMC,Sevoflurane acts on ubiquitination-proteasome pathway to reduce postsynaptic density 95 levels in young mice,http://dx.doi.org/10.1097/ALN.0000000000001889,PMC5685882,,,"BACKGROUND: Children with multiple exposures to anesthesia and surgery may have an increased risk of developing cognitive impairment. Sevoflurane, a commonly used anesthetic in children, has been reported to decrease levels of postsynaptic density protein 95 (PSD-95). However, the up-stream mechanisms and down-stream consequences of the sevoflurane-induced reduction in PSD-95 levels remains largely unknown. We therefore set out to assess whether sevoflurane acts on ubiquitination-proteasome pathway to facilitate PSD-95 degradation. METHODS: Six-day-old wild-type mice received anesthesia with 3% sevoflurane 2 hours daily for 3 days starting on postnatal (P) day 6. We determined effects of the sevoflurane anesthesia on mRNA, protein and ubiquitinated levels of PSD-95 in neurons, synaptosomes and hippocampus of young mice. Cognitive function in the mice was determined at P31 by using Morris Water Maze. Proteasome inhibitor MG132 and E3 ligase mouse double mutant 2 homolog inhibitor Nutlin-3 were used for the interaction studies. RESULTS: The sevoflurane anesthesia decreased protein, but not mRNA, levels of PSD-95, and reduced ubiquitinated PSD-95 levels in neurons, synaptosomes, and hippocampus of young mice. Both MG132 and Nutlin-3 blocked these sevoflurane-induced effects. Sevoflurane promoted the interaction of mouse double mutant 2 homolog and PSD-95 in neurons. Finally, MG132 and Nutlin-3 ameliorated the sevoflurane-induced cognitive impairment in the mice. CONCLUSIONS: These data suggest that sevoflurane acts on the ubiquitination-proteasome pathway to facilitate PSD-95 degradation, which then decreases PSD-95 levels, leading to cognitive impairment in young mice. These studies would further promote the mechanistic investigation of anesthesia neurotoxicity in the developing brain.",,"['Lu, Han', 'Liufu, Ning', 'Dong, Yuanlin', 'Xu, Guanghong', 'Zhang, Yiying', 'Shu, Liqi', 'Soriano, Sulpicio G.', 'Zheng, Hui', 'Yu, Buwei', 'Xie, Zhongcong']",,,,
,PMC,Viral enteritis in calves,,PMC5680732,,,"A complex community of bacteria, viruses, fungi, protists, and other microorganisms inhabit the gastrointestinal tract of calves and play important roles in gut health and disease. The viral component of the microbiome (the virome) is receiving increasing attention for its role in neonatal calf diarrhea (NCD). Rotavirus and coronavirus have for a long time been associated with NCD and commercial vaccines have been produced against these agents. Recently, several other viruses which may play a role in diarrhea have been discovered in calf fecal samples, mostly by sequence-based methods. These viruses include torovirus, norovirus, nebovirus, astrovirus, kobuvirus, and enterovirus. Most studies have involved epidemiologic investigations seeking to show association with diarrhea for each virus alone or in combination with potential pathogens. However, determining the contribution of these viruses to calf diarrhea has been challenging and much uncertainty remains concerning their roles as primary pathogens, co-infection agents, or commensals.",,"['Gomez, Diego E.', 'Weese, J. Scott']",,,,
,PMC,Harveian Oration 2017: Triumphs and challenges in a world shaped by medicine,http://dx.doi.org/10.7861/clinmedicine.17-6-537,PMC6297683,,,,,"Whitty, Christopher JM",,,,
,PMC,Respiratory Syncytial Virus and Other Non-influenza Respiratory Viruses in Older Adults,http://dx.doi.org/10.1016/j.idc.2017.07.006,PMC5846091,,,"Respiratory viral infections may cause serious complications for older adults, including residents of long-term care facilities (LTCFs). While influenza is the most common cause of viral respiratory infections among older adults, several other respiratory viruses also cause significant morbidity and mortality, most notably respiratory syncytial virus. Other noninfluenza respiratory viral pathogens include human metapneumovirus, parainfluenza virus, rhinovirus, coronavirus, and adenovirus. All of these may cause outbreaks among LTCF residents. Recently developed rapid diagnostic molecular tests may clarify the epidemiology of these viruses and have potential, through early identification, to limit the severity of outbreaks among older adults living in LTCFs.",,"['Kodama, Fumihiro', 'Nace, David A.', 'Jump, Robin L. P.']",,,,
,PMC,Powered air-purifying respirator use in healthcare: Effects on thermal sensations and comfort,http://dx.doi.org/10.1080/15459624.2017.1358817,PMC6198805,,,"Twelve subjects wore an N95 filtering facepiece respirator (N95 FFR), one tight-fitting full facepiece powered air-purifying respirator (PAPR), two loose-fitting PAPRs, and one elastomeric/PAPR hybrid for 1 hr each during treadmill walking at 5.6 km/hr while undergoing physiological and subjective response monitoring. No significant interaction (p ≥ .05) was noted between the five respirators in heart rate, respiratory rate, oxygen saturation, transcutaneous carbon dioxide, and perceptions of breathing effort or discomfort, exertion, facial heat, and overall body heat. Respirator deadspace heat/humidity were significantly greater for the N95 FFR, whereas tympanic forehead skin temperatures were significantly greater for the hybrid PAPR. Temperature of the facial skin covered by the respirator was equivalent for the N95 FFR and hybrid PAPR, and both were significantly higher than for the other three PAPRs. Perception of eye dryness was significantly greater for a tight-fitting full facepiece PAPR than the N95 FFR and hybrid PAPR. At a low-moderate work rate over 1 hr, effects on cardiopulmonary variables, breathing perceptions, and facial and overall body heat perceptions did not differ significantly between the four PAPRs and a N95 FFR, but the tight-fitting, full facepiece PAPR increased perceptions of eye dryness. The two loose-fitting PAPRs and the full facepiece tight-fitting PAPR ameliorated exercise-induced increases in facial temperature, but this did not translate to improved perception of facial heat and overall body heat.",,"['Powell, Jeffrey B.', 'Kim, Jung-Hyun', 'Roberge, Raymond J.']",,,,
,PMC,Infants with Atypical Presentations of Alveolar Capillary Dysplasia with Misalignment of the Pulmonary Veins (ACDMPV) who underwent Bilateral Lung Transplantation,http://dx.doi.org/10.1016/j.jpeds.2017.10.026,PMC5826830,,,"OBJECTIVE: To describe disease course, histopathology, and outcomes for infants with atypical presentations of alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) who underwent bilateral lung transplantation. STUDY DESIGN: We reviewed clinical history, diagnostic studies, explant histology, genetic results, and post-transplant course for 6 infants with atypical ACDMPV who underwent bilateral lung transplantation at St. Louis Children’s Hospital. We compared their histology with infants with classic ACDMPV and compared their outcomes with infants transplanted for other indications. RESULTS: In contrast to neonates with classic ACDPMV who present with severe hypoxemia and refractory pulmonary hypertension within hours of birth, none of the infants with atypical ACDMPV presented with progressive neonatal respiratory failure. Three infants had mild neonatal respiratory distress and received nasal cannula oxygen. Three other infants had no respiratory symptoms at birth and presented with hypoxemia and pulmonary hypertension at 2–3 months of age. Bilateral lung transplantation was performed at 4–20 months. Unlike in classic ACDMPV, histopathologic findings were not uniformly distributed and were not diffuse. Three subjects had apparent non-mosaic genetic defects involving FOXF1. Two infants had extra-pulmonary anomalies (posterior urethral valves, inguinal hernia). Three transplanted children are alive at 5–16 years, similar to outcomes for infants transplanted for other indications. Lung explants from infants with atypical ACDMPV demonstrated diagnostic but nonuniform histopathologic findings. CONCLUSIONS: One and 5-year survival rates for infants with atypical ACDM are similar to infants transplanted for other indications. Given the clinical and histopathologic spectra, ACDMPV should be considered in infants with hypoxemia and pulmonary hypertension, even beyond the newborn period.",,"['Towe, Christopher T.', 'White, Frances V.', 'Grady, R. Mark', 'Sweet, Stuart C.', 'Eghtesady, Pirooz', 'Wegner, Daniel J.', 'Sen, Partha', 'Szafranski, Przemyslaw', 'Stankiewicz, Pawel', 'Hamvas, Aaron', 'Cole, F. Sessions', 'Wambach, Jennifer A.']",,,,
,PMC,Acute rejection,http://dx.doi.org/10.21037/jtd.2017.11.83,PMC5757020,,,"Despite induction immunosuppression and the use of aggressive maintenance immunosuppressive regimens, acute allograft rejection following lung transplantation is still a problem with important diagnostic and therapeutic challenges. As well as causing early graft loss and mortality, acute rejection also initiates the chronic alloimmune responses and airway-centred inflammation that predispose to bronchiolitis obliterans syndrome (BOS), also known as chronic lung allograft dysfunction (CLAD), which is a major source of morbidity and mortality after lung transplantation. Cellular responses to human leukocyte antigens (HLAs) on the allograft have traditionally been considered the main mechanism of acute rejection, but the influence of humoral immunity is increasingly recognised. As with other several other solid organ transplants, antibody-mediated rejection (AMR) is now a well-accepted and distinct clinical entity in lung transplantation. While acute cellular rejection (ACR) has defined histopathological criteria, transbronchial biopsy is less useful in AMR and its diagnosis is complicated by challenges in the measurement of antibodies directed against donor HLA, and a determination of their significance. Increasing awareness of the importance of non-HLA antigens further clouds this issue. Here, we review the pathophysiology, diagnosis, clinical presentation and treatment of ACR and AMR in lung transplantation, and discuss future potential biomarkers of both processes that may forward our understanding of these conditions.",,"['Benzimra, Mark', 'Calligaro, Greg L.', 'Glanville, Allan R.']",,,,
,PMC,The coronavirus nucleocapsid protein is ADP-ribosylated,http://dx.doi.org/10.1016/j.virol.2017.11.020,PMC5871557,,,"ADP-ribosylation is a common post-translational modification, although how it modulates RNA virus infection is not well understood. While screening for ADP-ribosylated proteins during coronavirus (CoV) infection, we detected a ~55 kDa ADP-ribosylated protein in mouse hepatitis virus (MHV)-infected cells and in virions, which we identified as the viral nucleocapsid (N) protein. The N proteins of porcine epidemic diarrhea virus (PEDV), severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV were also ADP-ribosylated. ADP-ribosylation of N protein was also observed in cells exogenously expressing N protein by transduction using Venezuelan equine encephalitis virus replicon particles (VRPs). However, plasmid-derived N protein was not ADP-ribosylated following transient transfection but was ADP-ribosylated after MHV infection, indicating that this modification requires virus infection. In conclusion, we have identified a novel post-translation modification of the CoV N protein that may play a regulatory role for this important structural protein.",,"['Grunewald, Matthew E.', 'Fehr, Anthony R.', 'Athmer, Jeremiah', 'Perlman, Stanley']",,,,
,PMC,Interferon-Stimulated Genes as Enhancers of Antiviral Innate Immune Signaling,http://dx.doi.org/10.1159/000484258,PMC5969054,,,"The ability of a host to curb a viral infection is heavily reliant on the effectiveness of an initial antiviral innate immune response, resulting in the upregulation of interferon (IFN) and, subsequently, IFN-stimulated genes (ISGs). ISGs serve to mount an antiviral state within a host cell, and although the specific antiviral function of a number of ISGs has been characterized, the function of many of these ISGs remains to be determined. Recent research has uncovered a novel role for a handful of ISGs, some of them directly induced by IFN regulatory factor 3 in the absence of IFN itself. These ISGs, most with potent antiviral activity, are also able to augment varying arms of the innate immune response to viral infection, thereby strengthening this response. This new understanding of the role of ISGs may, in turn, help the recent advancement of novel therapeutics aiming to augment innate signaling pathways in an attempt to control viral infection and pathogenesis.",,"['Crosse, Keaton M.', 'Monson, Ebony A.', 'Beard, Michael R.', 'Helbig, Karla J.']",,,,
,PMC,"Classic Spotlight, 2014 and 2015: Articles of Significant Interest Selected from the Journal of Virology Archives by the Editors",http://dx.doi.org/10.1128/JVI.01665-17,PMC5709588,,,,,,,,,
,PMC,Development of Middle East Respiratory Syndrome Coronavirus vaccines – advances and challenges,http://dx.doi.org/10.1080/21645515.2017.1389362,PMC5806638,,,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging pathogen with the potential to pose a threat to global public health. Sporadic cases and outbreaks continue to be reported in the Middle East, and case fatality rates remain high at approximately 36% globally. No specific preventive or therapeutic countermeasures currently exist. A safe and effective vaccine could play an important role in protecting against the threat from MERS-CoV. This review discusses human vaccine candidates currently under development, and explores viral characteristics, molecular epidemiology and immunology relevant to MERS-CoV vaccine development. At present, a DNA vaccine candidate has begun a human clinical trial, while two vector-based candidates will very soon begin human trials. Protein-based vaccines are still at pre-clinical stage. Challenges to successful development include incomplete understanding of viral transmission, pathogenesis and immune response (in particular at the mucosal level), no optimal animal challenge models, lack of standardized immunological assays, and insufficient sustainable funding.",,"['Cho, Heeyoun', 'Excler, Jean-Louis', 'Kim, Jerome H.', 'Yoon, In-Kyu']",,,,
,PMC,The IFN response in bats displays distinctive ISG expression kinetics with atypical RNASEL induction(),http://dx.doi.org/10.4049/jimmunol.1701214,PMC5736455,,,"Bats host a large number of zoonotic viruses, including several viruses that are highly pathogenic to other mammals. The mechanisms underlying this rich viral diversity are unknown, but they may be linked to unique immunological features that allow bats to act as asymptomatic viral reservoirs. Vertebrates respond to viral infection by inducing interferons (IFNs), which trigger antiviral defenses through interferon-stimulated gene (ISG) expression. While the IFN system of several bats is characterized at the genomic level, less is known about bat IFN-mediated transcriptional responses. Here, we show that IFN signaling in bat cells from the black flying fox (Pteropus alecto) consists of both conserved and unique ISG expression profiles. In IFN-stimulated cells, bat ISGs comprise two unique temporal subclusters with similar early induction kinetics but distinct late-phase declines. By contrast, human ISGs lack this decline phase and remained elevated for longer periods. Notably, in unstimulated cells, bat ISGs were expressed more highly than their human counterparts. We also found that the antiviral effector RNASEL, which is not an ISG in humans, is highly IFN-inducible in black flying fox cells and contributes to cell intrinsic control of viral infection. These studies reveal distinctive innate immune features that may underlie a unique virus-host relationship in bats.",,"['De La Cruz-Rivera, Pamela C.', 'Kanchwala, Mohammed', 'Liang, Hanquan', 'Kumar, Ashwani', 'Wang, Lin-Fa', 'Xing, Chao', 'Schoggins, John W.']",,,,
,PMC,Genotyping and phylogenetic analysis of infectious bronchitis virus isolated from broiler chickens in Kashmir,http://dx.doi.org/10.1007/s13337-017-0416-2,PMC5747838,,,"Infectious bronchitis virus (IBV) is responsible for significant economic losses to the poultry industry across the world. The enormous genetic diversity of IBV poses difficulty in diagnosing and controlling the virus. To understand the nature of IBV prevalent in the Kashmir Himalayas, we characterized two field strains, isolated from non-immunized broiler chickens, by sequence and phylogenetic analysis of S1 subunit of the spike glycoprotein. The analysis revealed both the isolates are identical to each other, with nucleotide and amino acid sequence identities of 99.4% and 98.4%, respectively. They exhibit variable sequence divergence in the S1 gene to that of the reference serotypes. Both are of “Massachusetts type” belonging to GI-1 lineage of the IBV génotype. The phylogenetic analysis revealed both of the isolates clustered into the same branch as that of many IBV strains recently reported from China and Iran. Likely, these regionally-related isolates represent revertant vaccine strains which may have been disseminated across the region by wild migratory birds. This study provides the first report of molecular evidence and phylogenetic characterization of the IBV from the Kashmir Himalayas and implicate the possible role of wild migratory birds in the spread of IBV in the region. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13337-017-0416-2) contains supplementary material, which is available to authorized users.",,"['Parveen, Rafia', 'Farooq, Iqra', 'Ahangar, Showkat', 'Nazki, Salik', 'Dar, Zahoor', 'Dar, Tanveer', 'Kamil, Shayaib', 'Dar, Pervaiz']",,,,
,PMC,Functional 5′ UTR mRNA structures in eukaryotic translation regulation and how to find them,http://dx.doi.org/10.1038/nrm.2017.103,PMC5820134,,,"RNA molecules can fold into intricate shapes that can provide an additional layer of control of gene expression beyond that of their sequence. In this Review, we discuss the current mechanistic understanding of structures in 5′ untranslated regions (UTRs) of eukaryotic mRNAs and the emerging methodologies used to explore them. These structures may regulate cap-dependent translation initiation through helicase-mediated remodelling of RNA structures and higher-order RNA interactions, as well as cap-independent translation initiation through internal ribosome entry sites (IRESs), mRNA modifications and other specialized translation pathways. We discuss known 5′ UTR RNA structures and how new structure probing technologies coupled with prospective validation, particularly compensatory mutagenesis, are likely to identify classes of structured RNA elements that shape post-transcriptional control of gene expression and the development of multicellular organisms.",,"['Leppek, Kathrin', 'Das, Rhiju', 'Barna, Maria']",,,,
,PMC,Extensive homeostatic T cell phenotypic variation within the Collaborative Cross,http://dx.doi.org/10.1016/j.celrep.2017.10.093,PMC5728448,,,"The Collaborative Cross (CC) is a panel of reproducible recombinant inbred mouse strains with high levels of standing genetic variation, thereby affording unprecedented opportunity to perform experiments in a small animal model containing controlled genetic diversity while allowing for genetic replicates. Here, we advance the utility of this unique mouse resource for immunology research, as it allows for both examination and genetic dissection of mechanisms behind adaptive immune states in mice with distinct and defined genetic makeups. This approach is founded on quantitative trait locus mapping: identifying genetically variant genome regions associated with phenotypic variance in traits-of-interest. Furthermore, the CC can be utilized for mouse model development; distinct strains have unique immunophenotypes and immune properties, making them suitable for research on particular diseases and infections. Here, we describe variation in cellular immune phenotypes across F1 crosses of CC strains, and reveal quantitative trait loci responsible for several immune phenotypes.",,"['Graham, Jessica B.', 'Swarts, Jessica L.', 'Mooney, Michael', 'Choonoo, Gabrielle', 'Jeng, Sophia', 'Miller, Darla R.', 'Ferris, Martin T.', 'McWeeney, Shannon', 'Lund, Jennifer M.']",,,,
,PMC,Immune responses in influenza A virus and human coronavirus infections: An ongoing battle between the virus and host,http://dx.doi.org/10.1016/j.coviro.2017.11.002,PMC5835172,,,"Respiratory viruses, especially influenza A viruses and coronaviruses such as MERS-CoV, represent continuing global threats to human health. Despite significant advances, much needs to be learned. Recent studies in virology and immunology have improved our understanding of the role of the immune system in protection and in the pathogenesis of these infections and of co-evolution of viruses and their hosts. These findings, together with sophisticated molecular structure analyses, omics tools and computer-based models, have helped delineate the interaction between respiratory viruses and the host immune system, which will facilitate the development of novel treatment strategies and vaccines with enhanced efficacy.",,"['Zheng, Jian', 'Perlman, Stanley']",,,,
,PMC,Human PBMC-transferred murine MHC class I/II-deficient NOG mice enable long-term evaluation of human immune responses,http://dx.doi.org/10.1038/cmi.2017.106,PMC6207709,,,"Immunodeficient mice engrafted with human peripheral blood cells are promising tools for in vivo analysis of human patient individual immune responses. However, when human peripheral blood mononuclear cells (PBMCs) are transferred into NOG (NOD/Shi-scid, IL-2rg (null)) mice, severe graft versus host disease (GVHD) hinders long term detailed analysis. Administration of human PBMCs into newly developed murine MHC class I- and class II-deficient NOG (NOG-dKO; NOG- Iab, B2m-double-knockout) mice showed sufficient engraftment of human immune cells with little sign of GVHD. Immunization with influenza vaccine resulted in an increase in influenza-specific human IgG Ab, indicating induction of antigen-specific B cells in the NOG-dKO mice. Immunization with human dendritic cells pulsed with HLA-A2 restricted cytomegalovirus peptide induced specific cytotoxic T cells, indicating the induction of antigen-specific T cells in the NOG-dKO mice. Adoptive cell therapies (ACTs) using melanoma antigen recognized by T cells (MART-1)-specific TCR-transduced activated T cells showed strong tumor growth inhibition in NOG-dKO mice without any sign of GVHD accompanied by preferential expansion of the transferred MART-1-specific T cells. ACTs using cultured human melanoma infiltrating T cells also showed anti-tumor effects against autologous melanoma cells in NOG-dKO mice, in which changes in human cancer phenotypes by immune intervention, such as increased CD271 expression, could be evaluated. Therefore, NOG-dKO mice are useful tools for more detailed analysis of both the induction and effector phases of T-cell and B-cell responses for a longer period than regular NOG mice.",,"['Yaguchi, Tomonori', 'Kobayashi, Asuka', 'Inozume, Takashi', 'Morii, Kenji', 'Nagumo, Haruna', 'Nishio, Hiroshi', 'Iwata, Takashi', 'Ka, Yuyo', 'Katano, Ikumi', 'Ito, Ryoji', 'Ito, Mamoru', 'Kawakami, Yutaka']",,,,
,PMC,The GAIT Translational Control System,http://dx.doi.org/10.1002/wrna.1441,PMC5815886,,,"The interferon (IFN)-γ-activated inhibitor of translation (GAIT) system directs transcript-selective translational control of functionally-related genes. In myeloid cells, IFN-γ induces formation of a multiprotein GAIT complex that binds structural GAIT elements in the 3' untranslated regions (UTR) of multiple inflammation-related mRNAs, including ceruloplasmin and VEGF-A, and represses their translation. The human GAIT complex is a heterotetramer containing glutamyl-prolyl tRNA synthetase (EPRS), NS1-associated protein 1 (NSAP1), ribosomal protein L13a (L13a), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). A network of IFN-γ-stimulated kinases regulates recruitment and assembly of GAIT complex constituents. Activation of Cdk5, mTORC1, and S6K1 kinases induces EPRS release from its parental multi-aminoacyl tRNA synthetase complex to join NSAP1 in a “pre-GAIT” complex. Subsequently, the DAPK-ZIPK kinase axis phosphorylates L13a, inducing release from the 60S ribosomal subunit and binding to GAPDH. The subcomplexes join to form the functional GAIT complex. Each constituent has a distinct role in the GAIT system. EPRS binds the GAIT element in target mRNAs, NSAP1 negatively regulates mRNA binding, L13a binds eIF4G to block ribosome recruitment, and GAPDH shields L13a from proteasomal degradation. The GAIT system is susceptible to genetic and condition-specific regulation. An N-terminus EPRS truncate is a dominant-negative inhibitor ensuring a “translational trickle” of target transcripts. Also, hypoxia and oxidatively-modified lipoproteins regulate GAIT activity. Mouse models exhibiting absent or genetically-modified GAIT complex constituents are beginning to elucidate the physiological role of the GAIT system, particularly in the resolution of chronic inflammation. Finally, GAIT-like systems in proto-chordates suggests an evolutionarily conserved role of the pathway in innate immunity.",,"['Arif, Abul', 'Yao, Peng', 'Terenzi, Fulvia', 'Jia, Jie', 'Ray, Partho Sarothi', 'Fox, Paul L.']",,,,
,PMC,Syndromic Panel-Based Testing in Clinical Microbiology,http://dx.doi.org/10.1128/CMR.00024-17,PMC5740973,,,"The recent development of commercial panel-based molecular diagnostics for the rapid detection of pathogens in positive blood culture bottles, respiratory specimens, stool, and cerebrospinal fluid has resulted in a paradigm shift in clinical microbiology and clinical practice. This review focuses on U.S. Food and Drug Administration (FDA)-approved/cleared multiplex molecular panels with more than five targets designed to assist in the diagnosis of bloodstream, respiratory tract, gastrointestinal, or central nervous system infections. While these panel-based assays have the clear advantages of a rapid turnaround time and the detection of a large number of microorganisms and promise to improve health care, they present certain challenges, including cost and the definition of ideal test utilization strategies (i.e., optimal ordering) and test interpretation.",,"['Ramanan, Poornima', 'Bryson, Alexandra L.', 'Binnicker, Matthew J.', 'Pritt, Bobbi S.', 'Patel, Robin']",,,,
,PMC,Nano-Magnetic System For Rapid Diagnosis Of Acute Infection,http://dx.doi.org/10.1021/acsnano.7b06074,PMC6296367,,,"Pathogen activated antibody-secreting cells (ASCs) produce and secrete antigen-specific antibodies. ASCs are detectable in the peripheral blood as early as 3 days after antigen exposure, which makes ASCs a potential biomarker for early disease detection. Here we present a Magnetic Capture and Detection (MCD) assay for sensitive, on-site detection of ASCs. In this approach, ASCs are enriched through magnetic capture, and secreted antibodies are magnetically detected by a miniaturized nuclear magnetic resonance (μNMR) system. This approach is based entirely on magnetics which supports high contrast against biological background, and simplifies assay procedures. We advanced the MCD system by i) synthesizing magnetic nanoparticles (MNPs) with high magnetic moments for both cell capture and antibody detection, ii) developing a miniaturized magnetic device for high-yield cell capture, and iii) optimizing the μNMR assay for antibody detection. Antibody responses targeting hemolysin E (HlyE) can accurately identify individuals with acute enteric fever. As a proof-of-concept, we applied MCD to detect antibodies produced by HlyE-specific hybridoma cells. The MCD achieved high sensitivity in detecting antibodies secreted from as few as 5 hybridoma cells (50 cells/mL). Importantly, the assay could be performed with whole blood with minimal sample processing.",,"['Park, Ki Soo', 'Kim, Hoyoung', 'Kim, Soojin', 'Lee, Kyungheon', 'Park, Sohyeon', 'Song, Jun', 'Min, Changwook', 'Khanam, Farhana', 'Rashu, Rasheduzzaman', 'Bhuiyan, Taufiqur Rahman', 'Ryan, Edward T.', 'Qadri, Firdausi', 'Weissleder, Ralph', 'Cheon, Jinwoo', 'Charles, Richelle C.', 'Lee, Hakho']",,,,
,PMC,Macrophage scavenger receptor 1 contributes to pathogenesis of fulminant hepatitis via neutrophil-mediated complement activation,http://dx.doi.org/10.1016/j.jhep.2017.11.010,PMC5951742,,,"BACKGROUND & AIMS: The macrophage scavenger receptor 1 (Msr1, also called SRA) is a pattern recognition receptor primarily expressed on myeloid cells, which plays an important role in the maintenance of immune homeostasis. Since MSR1 expression was upregulated in the livers of patients with fulminant hepatitis (FH), we investigated the functional mechanism of Msr1 in FH pathogenesis. METHODS: Msr1-deficient (Msr1(−/−)) mice and their wild-type (WT) littermates were infected with mouse hepatitis virus strain-A59 (MHV-A59) to induce FH, and the levels of tissue damage, serum alanine aminotransferase, inflammatory cytokines and complement component 5a (C5a) were measured and compared. Liver injury was studied after MHV infection with or without neutrophil depletion. RESULTS: Our results showed that Msr1(−/−) mice were resistant to MHV-induced hepatitis. Treatment with the C5a receptor antagonist (C5aRa) diminished the differences in inflammatory responses and liver injury between MHV-infected wild-type and Msr1(−/−) mice, suggesting that C5a-induced proinflammatory response plays a critical role in the Msr1-mediated regulation of FH pathogenesis. We demonstrated that Msr1 efficiently enhanced transforming growth factor-activated kinase-1 phosphorylation in neutrophils upon MHV-A59 stimulation, thereby promoting the activation of the extracellular signal-regulated kinase pathway and subsequent NETosis formation. Moreover, we provided evidence that blockage of Msr1 attenuated the liver damage caused by MHV-A59 infection. CONCLUSIONS: Msr1 promotes the pathogenesis of virus-induced FH by enhancing induction of neutrophil NETosis and subsequent complement activation. Targeting Msr1 may be employed as a new immunotherapeutic strategy for FH. LAY SUMMARY: Virus-induced fulminant hepatitis (FH) is a disease with a high mortality worldwide. Enhanced levels of macrophage scavenger receptor 1 (Msr1) in the liver of patients with FH and of murine experimental FH indicated Msr1 plays a role in the pathogenesis of FH. Herein, we demonstrate that mice deficient in Msr1 are resistant to FH induced by MHV-A59, and the Msr1 inhibitor fucoidan suppresses the progression of FH in mice. Our study suggests that use of drugs inhibiting MSR1 function could be beneficial to patients with FH.",,"['Tang, Yuan', 'Li, Huifang', 'Li, Junru', 'Liu, Yunzhi', 'Li, Yanli', 'Zhou, Jing', 'Zhou, Jia', 'Lu, Xiao', 'Zhao, Wei', 'Hou, Jinlin', 'Wang, Xiang-Yang', 'Chen, Zhengliang', 'Zuo, Daming']",,,,
,PMC,"Classic Spotlight, 2012 and 2013: Articles of Significant Interest Selected from the Journal of Virology Archives by the Editors",http://dx.doi.org/10.1128/JVI.01577-17,PMC5686745,,,,,,,,,
,PMC,Protective Humoral Immunity in the Central Nervous System Requires Peripheral CD19-Dependent Germinal Center Formation following Coronavirus Encephalomyelitis,http://dx.doi.org/10.1128/JVI.01352-17,PMC5686739,,,"B cell subsets with phenotypes characteristic of naive, non-isotype-switched, memory (B(mem)) cells and antibody-secreting cells (ASC) accumulate in various models of central nervous system (CNS) inflammation, including viral encephalomyelitis. During neurotropic coronavirus JHMV infection, infiltration of protective ASC occurs after T cell-mediated viral control and is preceded by accumulation of non-isotype-switched IgD(+) and IgM(+) B cells. However, the contribution of peripheral activation events in cervical lymph nodes (CLN) to driving humoral immune responses in the infected CNS is poorly defined. CD19, a signaling component of the B cell receptor complex, is one of multiple regulators driving B cell differentiation and germinal center (GC) formation by lowering the threshold of antigen-driven activation. JHMV-infected CD19(−/−) mice were thus used to determine how CD19 affects CNS recruitment of B cell subsets. Early polyclonal ASC expansion, GC formation, and virus-specific ASC were all significantly impaired in CLN of CD19(−/−) mice compared to wild-type (WT) mice, consistent with lower and unsustained virus-specific serum antibody (Ab). ASC were also significantly reduced in the CNS, resulting in increased infectious virus during persistence. Nevertheless, CD19 deficiency did not affect early CNS IgD(+) B cell accumulation. The results support the notion that CD19-independent factors drive early B cell mobilization and recruitment to the infected CNS, while delayed accumulation of virus-specific, isotype-switched ASC requires CD19-dependent GC formation in CLN. CD19 is thus essential for both sustained serum Ab and protective local Ab within the CNS following JHMV encephalomyelitis. IMPORTANCE CD19 activation is known to promote GC formation and to sustain serum Ab responses following antigen immunization and viral infections. However, the contribution of CD19 in the context of CNS infections has not been evaluated. This study demonstrates that antiviral protective ASC in the CNS are dependent on CD19 activation and peripheral GC formation, while accumulation of early-recruited IgD(+) B cells is CD19 independent. This indicates that IgD(+) B cells commonly found early in the CNS do not give rise to local ASC differentiation and that only antigen-primed, peripheral GC-derived ASC infiltrate the CNS, thereby limiting potentially harmful nonspecific Ab secretion. Expanding our understanding of activation signals driving CNS migration of distinct B cell subsets during neuroinflammatory insults is critical for preventing and managing acute encephalitic infections, as well as preempting reactivation of persistent viruses during immune-suppressive therapies targeting B cells in multiple sclerosis (MS), such as rituximab and ocrelizumab.",,"['Atkinson, Jeffrey R.', 'Bergmann, Cornelia C.']",,,,
,PMC,Structurally Guided Removal of DeISGylase Biochemical Activity from Papain-Like Protease Originating from Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.01067-17,PMC5686735,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging human pathogen that is the causative agent for Middle East respiratory syndrome (MERS). With MERS outbreaks resulting in over 35% fatalities and now spread to 27 countries, MERS-CoV poses a significant ongoing threat to global human health. As part of its viral genome, MERS-CoV encodes a papain-like protease (PLpro) that has been observed to act as a deubiquitinase and deISGylase to antagonize type I interferon (IFN-I) immune pathways. This activity is in addition to its viral polypeptide cleavage function. Although the overall impact of MERS-CoV PLpro function is observed to be essential, difficulty has been encountered in delineating the importance of its separate functions, particularly its deISGylase activity. As a result, the interface of MERS-CoV and human interferon-stimulated gene product 15 (hISG15) was probed with isothermal calorimetry, which suggests that the C-terminal domain of hISG15 is principally responsible for interactions. Subsequently, the structure of MERS-CoV PLpro was solved to 2.4 Å in complex with the C-terminal domain of hISG15. Utilizing this structural information, mutants were generated that lacked appreciable deISGylase activity but retained wild-type deubiquitinase and peptide cleavage activities. Hence, this provides a new platform for understanding viral deISGylase activity within MERS-CoV and other CoVs. IMPORTANCE Coronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV), encode a papain-like protease (PLpro) that possesses the ability to antagonize interferon immune pathways through the removal of ubiquitin and interferon-stimulated gene product 15 (ISG15) from target proteins. The lack of CoV proteases with attenuated deISGylase activity has been a key obstacle in delineating the impact between deubiquitinase and deISGylase activities on viral host evasion and pathogenesis. Here, biophysical techniques revealed that MERS-CoV PLpro chiefly engages human ISG15 through its C-terminal domain. The first structure of MERS-CoV PLpro in complex with this domain exposed the interface between these two entities. Employing these structural insights, mutations were employed to selectively remove deISGylase activity with no appreciable impact on its other deubiquitinase and peptide cleavage biochemical properties. Excitingly, this study introduces a new tool to probe the pathogenesis of MERS-CoV and related viruses through the removal of viral deISGylase activity.",,"['Daczkowski, Courtney M.', 'Goodwin, Octavia Y.', 'Dzimianski, John V.', 'Farhat, Jonathan J.', 'Pegan, Scott D.']",,,,
,PMC,Probing the metastable state of influenza hemagglutinin,http://dx.doi.org/10.1074/jbc.M117.815043,PMC5766969,,,"Viral entry into host cells is mediated by membrane proteins in a metastable state that transition to a more stable state upon a stimulus. For example, in the influenza envelope protein hemagglutinin (HA), the low pH in the endosome triggers a transition from the metastable prefusion conformation to the stable fusion conformation. To identify probes that interfere with HA function, here we screened a library of H7 HA peptides for inhibition of H7 HA-mediated entry. We discovered a peptide, PEP87 (WSYNAELLVAMENQHTI), that inhibited H7 and H5 HA-mediated entry. PEP87 corresponds to a highly conserved helical region of the HA2 subunit of HA that self-interacts in the neutral pH conformation. Mutagenesis experiments indicated that PEP87 binds to its native region in the HA trimer. We also found that PEP87 is unstructured in isolation but tends to form a helix as evidenced by CD and NMR studies. Fluorescence, chemical cross-linking, and saturation transfer difference NMR data suggested that PEP87 binds to the neutral pH conformation of HA and disrupts the HA structure without affecting its oligomerization state. Together, this work provides support for a model in which PEP87 disrupts HA function by displacing native interactions of the neutral pH conformation. Moreover, our observations indicate that the HA prefusion structure (and perhaps the metastable states of other viral entry proteins) is more dynamic with transient motions being larger than generally appreciated. These findings also suggest that the ensemble of prefusion structures presents many potential sites for targeting in therapeutic interventions.",,"['Kingsley, Carolyn N.', 'Antanasijevic, Aleksandar', 'Palka-Hamblin, Helena', 'Durst, Matthew', 'Ramirez, Benjamin', 'Lavie, Arnon', 'Caffrey, Michael']",,,,
,PMC,Progress towards the clinical translation of bio-inspired peptide and protein assemblies,http://dx.doi.org/10.1002/adhm.201700930,PMC5858183,,,"Supramolecular materials composed of proteins and peptides have been receiving considerable attention towards a range of diseases and conditions from vaccines to drug delivery. Owing to the relative newness of this class of materials, the bulk of work to date has been preclinical. However, examples of approved treatments particularly in vaccines, dentistry, and hemostasis are demonstrating the translational potential of supramolecular polypeptides. Here we describe critical milestones in the clinical development of this class of materials and describe currently approved supramolecular polypeptide therapies. Additional examples of not-yet-approved materials that are steadily advancing towards clinical use are also featured. Spherical assemblies such as virus-like particles (VLPs), designed protein nanoparticles, and spherical peptide amphiphiles are highlighted, followed by fiber-forming systems such as fibrillizing peptides, fiber-forming peptide-amphiphiles, and filamentous bacteriophages.",,"['Hainline, Kelly M.', 'Fries, Chelsea N.', 'Collier, Joel H.']",,,,
,PMC,Identification of phlebovirus and arenavirus RNA sequences that stall and repress the exoribonuclease XRN1,http://dx.doi.org/10.1074/jbc.M117.805796,PMC5766927,,,"Regulated mRNA decay plays a vital role in determining both the level and quality of cellular gene expression. Viral RNAs must successfully evade this host RNA decay machinery to establish a productive infection. One way for RNA viruses to accomplish this is to target the cellular exoribonuclease XRN1, because this enzyme is accessible in the cytoplasm and plays a major role in mRNA decay. Members of the Flaviviridae use RNA structures in their 5′- or 3′-untranslated regions to stall and repress XRN1, effectively stabilizing viral RNAs while also causing significant dysregulation of host cell mRNA stability. Here, we use a series of biochemical assays to demonstrate that the 3′-terminal portion of the nucleocapsid (N) mRNA of Rift Valley fever virus, a phlebovirus of the Bunyaviridae family, also can effectively stall and repress XRN1. The region responsible for impeding XRN1 includes a G-rich portion that likely forms a G-quadruplex structure. The 3′-terminal portions of ambisense-derived transcripts of multiple arenaviruses also stalled XRN1. Therefore, we conclude that RNAs from two additional families of mammalian RNA viruses stall and repress XRN1. This observation. emphasizes the importance and commonality of this viral strategy to interfere with the 5′-to-3′-exoribonuclease component of the cytoplasmic RNA decay machinery",,"['Charley, Phillida A.', 'Wilusz, Carol J.', 'Wilusz, Jeffrey']",,,,
,PMC,"An IRF-3, -5, -7-independent pathway of dengue viral resistance utilizes IRF-1 to stimulate type I and II interferon responses",http://dx.doi.org/10.1016/j.celrep.2017.10.054,PMC5696617,,,"Interferon-regulatory factors (IRFs) are a family of transcription factors (TFs) that translate viral recognition into antiviral responses, including type I interferon (IFN) production. Dengue virus (DENV) and other clinically important flaviviruses are suppressed by type I IFN. While mice lacking the type I IFN receptor (Ifnar1(−/−)) succumb to DENV infection, we found that mice deficient in three TFs controlling type I IFN production, Irf3(−/−)xIrf5(−/−)xIrf7(−/−) triple knockout (TKO), survive DENV challenge. DENV infection of TKO mice resulted in minimal type I IFN production but a robust type II IFN (IFNγ) response. Using loss-of-function approaches for various molecules, we demonstrate that the IRF-3, -5, -7-independent pathway utilizes predominantly IFNγ, and to a lesser degree type I IFNs. This pathway signals via IRF-1 to stimulate IL-12 production and IFNγ response. These results reveal a key antiviral role for IRF-1 by activating both type I and II IFN responses during DENV infection.",,"['Carlin, Aaron F.', 'Plummer, Emily M.', 'Vizcarra, Edward A.', 'Sheets, Nicholas', 'Joo, Yunichel', 'Tang, William', 'Day, Jeremy', 'Greenbaum, Jay', 'Glass, Christopher K.', 'Diamond, Michael S.', 'Shresta, Sujan']",,,,
,PMC,"Dynamics of Bacterial Colonization With Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis During Symptomatic and Asymptomatic Viral Upper Respiratory Tract Infection",http://dx.doi.org/10.1093/cid/cix941,PMC6019034,,,"BACKGROUND: Virus is detected in about 80% of upper respiratory tract infections (URTIs) in children and is also detectable in the nasopharynx of 30% of asymptomatic children. The effect of asymptomatic viral infection on the dynamics of bacterial density and colonization of the nasopharynx has not been reported. The current study was performed to assess the presence and density of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the nasopharynx of 4–7-year-old children during URTI and when well. METHODS: Nasal samples were obtained during 4 surveillance periods when children were asymptomatic and whenever they had symptoms of URTI. Respiratory viruses and bacterial pathogens were identified and quantified using polymerase chain reaction. RESULTS: The proportion of children colonized with all 3 bacteria was higher during visits for acute URTI than during asymptomatic surveillance visits. Mean bacterial densities were significantly higher at all visits for all 3 pathogens when a virus was detected. The differences between the means were 1.0, 0.4, and 0.7 log(10) colony-forming unit equivalents per milliliter for S. pneumoniae, H. influenzae, and M. catarrhalis, respectively, compared with visits in which virus was not detected. The percentage of children colonized and density were also higher at asymptomatic visits in which virus was detected than at visits in which virus was not detected. CONCLUSION: The density and frequency of colonization with S. pneumoniae, H. influenzae, and M. catarrhalis in nasal wash samples increase during periods of both symptomatic and asymptomatic viral infection. Increases in bacterial colonization observed during asymptomatic viral infection were nearly the same magnitude as when children were symptomatic.",,"['DeMuri, Gregory P', 'Gern, James E', 'Eickhoff, Jens C', 'Lynch, Susan V', 'Wald, Ellen R']",,,,
,PMC,11β-hydroxysteroid dehydrogenases as targets in the treatment of steroid-associated femoral head necrosis using antler extract,http://dx.doi.org/10.3892/etm.2017.5459,PMC5772940,,,"The aim of the present study was to investigate the therapeutic effect of deer antler extract on avascular necrosis of the femoral head (ANFH) induced by steroids, and to confirm that 11β-hydroxysteroid dehydrogenases (11β-HSD) are one of the targets of treatment with antler extract. A total of 30 rabbits were randomly divided into 5 groups (n=6): A control, ANFH, ANFH + antler (250 mg/kg), ANFH + antler (500 mg/kg) and ANFH + antler (1,000 mg/kg) group. Rabbits in the experimental groups were injected with methylprednisolone and horse serum to establish a steroid-induced ANFH (SANFH) model. Rabbits in the ANFH + antler (250 mg/kg), ANFH + antler (500 mg/kg) and ANFH + antler (1,000 mg/kg) groups were treated with intraperitoneal injection of 250, 500 or 1,000 mg/kg antler extract/day, respectively, for 60 days. Serum samples were then extracted to determine total cholesterol (CT) and triglyceride levels, treat osteoblasts, measure 11β-HSD (11β-HSD1) and 11β-HSD2 and alkaline phosphatase (ALP) levels and cellular apoptosis, and determine the proportion of osteoblasts in each phase of the cell cycle. Serum CT and triglyceride levels in SANFH rabbits significantly decreased as the concentration of antler increased (P<0.05). 11β-HSD1 levels in the femoral heads of SANFH rabbits and osteoblasts following treatment with antler-containing serum decreased as the concentration of antler used increased, whereas levels of 11β-HSD1 increased significantly (P<0.05). The proliferation of osteoblasts and ALP levels in osteoblasts increased as the antler concentration increased, whereas the number of osteoblasts in the G0/G1 phase decreased significantly (P<0.05). The current study demonstrated that treatment with antler extract has a therapeutic effect on ANFH induced by steroids in rabbits and may regulate the expression of 11β-HSD in femoral heads and osteoblasts, as well as promoting the proliferation of osteoblasts.",,"['Pu, Ribusurong', 'Peng, Hao']",,,,
,PMC,Human Washington University Polyomavirus in Patients with Respiratory Tract Infection in Kuwait,http://dx.doi.org/10.1159/000485036,PMC5848483,,,"OBJECTIVE: To determine Washington University (WU) polyomavirus strains circulating among hospitalized patients with respiratory tract infections (RTI) in Kuwait. MATERIALS AND METHODS: Samples from 459 hospitalized children and adult RTI patients were screened for respiratory viruses by polymerase chain reaction from April 2013 to April 2016. The VP2 gene from WU virus (WUV)-positive samples was sequenced and subjected to phylogenetic analysis. RESULTS: Of the 459 hospitalized RTI patients, 18 (3.9$) patients were positive for WUV infection. WUV infection was common among children aged ≤11 years (9 patients, 50$). Among the 18 WUV-infected hospitalized patients, viral co-infection was detected in 9 patients (50$). The most common viruses associated with mixed infection were respiratory syncytial virus and human rhinovirus (2 patients, 11.1$ each). Of the 18 WUV-infected patients, 4 were sequenced and subjected to phylogenetic analysis. The circulating strains belong to type Ia and IIIb. CONCLUSION: This study enabled us to detect WUV among hospitalized RTI patients. Co-infection with other respiratory viruses was notable. Two circulating WUV genotypes (Ia and IIIb) were identified among hospitalized RTI patients in Kuwait.",,"['Essa, Sahar Sultan', 'Chehadeh, Wassim', 'Al-Nakib, Widad']",,,,
,PMC,Molecular survey of infectious agents associated with bovine respiratory disease in a beef cattle feedlot in southern Brazil,http://dx.doi.org/10.1177/1040638717739945,PMC6505859,,,"We investigated the occurrence of infectious pathogens during an outbreak of bovine respiratory disease (BRD) in a beef cattle feedlot in southern Brazil that has a high risk of developing BRD. Nasopharyngeal swabs were randomly collected from steers (n = 23) and assessed for the presence of infectious agents of BRD by PCR and/or RT-PCR assays. These included: Histophilus somni, Mannheimia haemolytica, Pasteurella multocida, Mycoplasma bovis, bovine respiratory syncytial virus (BRSV), bovine coronavirus (BCoV), bovine viral diarrhea virus (BVDV), bovine alphaherpesvirus 1 (BoHV-1), and bovine parainfluenza virus 3 (BPIV-3). Pulmonary sections of one steer that died with clinical BRD were submitted for pathology and molecular testing. The frequencies of the pathogens identified from the nasopharyngeal swabs were: H. somni 39% (9 of 23), BRSV 35% (8 of 23), BCoV 22% (5 of 23), and M. haemolytica 13% (3 of 23). PCR or RT-PCR assays did not identify P. multocida, M. bovis, BoHV-1, BVDV, or BPIV-3 from the nasopharyngeal swabs. Single and concomitant associations of infectious agents of BRD were identified. Fibrinous bronchopneumonia was diagnosed in one steer that died; samples were positive for H. somni and M. haemolytica by PCR. H. somni, BRSV, and BCoV are important disease pathogens of BRD in feedlot cattle in Brazil, but H. somni and BCoV are probably under-reported.",,"['Headley, Selwyn A.', 'Okano, Werner', 'Balbo, Luciana C.', 'Marcasso, Rogério A.', 'Oliveira, Thalita E.', 'Alfieri, Alice F.', 'Negri Filho, Luiz C.', 'Michelazzo, Mariana Z.', 'Rodrigues, Silvio C.', 'Baptista, Anderson L.', 'Saut, João Paulo E.', 'Alfieri, Amauri A.']",,,,
,PMC,Health Information–Seeking Patterns of the General Public and Indications for Disease Surveillance: Register-Based Study Using Lyme Disease,http://dx.doi.org/10.2196/publichealth.8306,PMC5696583,29109071,CC BY,"BACKGROUND: People using the Internet to find information on health issues, such as specific diseases, usually start their search from a general search engine, for example, Google. Internet searches such as these may yield results and data of questionable quality and reliability. Health Library is a free-of-charge medical portal on the Internet providing medical information for the general public. Physician’s Databases, an Internet evidence-based medicine source, provides medical information for health care professionals (HCPs) to support their clinical practice. Both databases are available throughout Finland, but the latter is used only by health professionals and pharmacies. Little is known about how the general public seeks medical information from medical sources on the Internet, how this behavior differs from HCPs’ queries, and what causes possible differences in behavior. OBJECTIVE: The aim of our study was to evaluate how the general public’s and HCPs’ information-seeking trends from Internet medical databases differ seasonally and temporally. In addition, we aimed to evaluate whether the general public’s information-seeking trends could be utilized for disease surveillance and whether media coverage could affect these seeking trends. METHODS: Lyme disease, serving as a well-defined disease model with distinct seasonal variation, was chosen as a case study. Two Internet medical databases, Health Library and Physician’s Databases, were used. We compared the general public’s article openings on Lyme disease from Health Library to HCPs’ article openings on Lyme disease from Physician’s Databases seasonally across Finland from 2011 to 2015. Additionally, media publications related to Lyme disease were searched from the largest and most popular media websites in Finland. RESULTS: Both databases, Health Library and Physician’s Databases, show visually similar patterns in temporal variations of article openings on Lyme disease in Finland from 2011 to 2015. However, Health Library openings show not only an increasing trend over time but also greater fluctuations, especially during peak opening seasons. Outside these seasons, publications in the media coincide with Health Library article openings only occasionally. CONCLUSIONS: Lyme disease–related information-seeking behaviors between the general public and HCPs from Internet medical portals share similar temporal variations, which is consistent with the trend seen in epidemiological data. Therefore, the general public’s article openings could be used as a supplementary source of information for disease surveillance. The fluctuations in article openings appeared stronger among the general public, thus, suggesting that different factors such as media coverage, affect the information-seeking behaviors of the public versus professionals. However, media coverage may also have an influence on HCPs. Not every publication was associated with an increase in openings, but the higher the media coverage by some publications, the higher the general public’s access to Health Library.",2017 Nov 6,"['Pesälä, Samuli', 'Virtanen, Mikko J', 'Sane, Jussi', 'Mustonen, Pekka', 'Kaila, Minna', 'Helve, Otto']",JMIR Public Health Surveill,,,
,PMC,A Tale of Two Viruses: Does Heterologous Flavivirus Immunity Enhance Zika Disease?,http://dx.doi.org/10.1016/j.tim.2017.10.004,PMC6530781,,,"The rise of Zika virus (ZIKV) and its unusual clinical manifestations provided ground for speculative debate. The clinical severity of secondary dengue virus (DENV) infections is associated with antibody-dependent enhancement (ADE), and it was recently suggested that previous exposure to DENV may worsen ZIKV clinical outcomes. In this Opinion article we analyze the relationship among different flaviviruses and ADE. We discuss new evidence obtained in non-human primates and human cohorts demonstrating that there is no correlation to ADE when ZIKV infection occurs in the presence of pre-existing DENV immunity. We propose a redefinition of ADE in the context of complex immunological flavivirus interactions to provide a more objective perspective when translating in vitro or in vivo observations into the clinical setting.",,"['Sariol, Carlos A.', 'Nogueira, Mauricio L.', 'Vasilakis, Nikos']",,,,
,PMC,Nuclear TRIM25 specifically targets influenza virus ribonucleoproteins to block the onset of RNA chain elongation,http://dx.doi.org/10.1016/j.chom.2017.10.003,PMC6309188,,,"TRIM25 is an E3 ubiquitin ligase that activates RIG-I to promote the anti-viral interferon response. The NS1 protein from all strains of influenza A virus bind TRIM25, although not all virus strains block the interferon response, suggesting alternative mechanisms for TRIM25 action. Here we present a nuclear role for TRIM25 in specifically restricting influenza A virus replication. TRIM25 inhibits viral RNA synthesis through a direct mechanism, independent of its ubiquitin ligase activity and the interferon pathway. This activity can be inhibited by the viral NS1 protein. TRIM25 inhibition of viral RNA synthesis results from its binding to viral ribonucleoproteins (vRNPs), the structures containing individual viral RNA segments, the viral polymerase, and multiple viral nucleoproteins. TRIM25 binding does not inhibit initiation of capped RNA-primed viral mRNA synthesis by the viral polymerase. Rather, the onset of RNA chain elongation is inhibited because TRIM25 prohibits the movement of RNA into the polymerase complex.",,"['Meyerson, Nicholas R.', 'Zhou, Ligang', 'Guo, Yusong R.', 'Zhao, Chen', 'Tao, Yizhi J.', 'Krug, Robert M.', 'Sawyer, Sara L.']",,,,
,PMC,"Infection prevention and control: Who is the judge, you or the guidelines?",http://dx.doi.org/10.1177/1757177417738332,PMC5956699,,,"OBJECTIVES: The aim of this study was to explore the attitudes and behaviours of registered nurses and their colleagues around the adoption of standard precautions in order to determine strategies to promote adherence. DESIGN: A qualitative exploratory descriptive design used interviews and focus group to collect data. SETTING: Registered nurses and registered midwifes from a tertiary metropolitan hospital took part in the study. PARTICIPANTS: A voluntary sample of 29 adults was recruited from the Australian nursing (n = 25) and midwifery (n = 4) workforce. There were six men (mean age = 36.83 years; SD = 8.93) and 23 women (mean age = 41.36 years; SD = 10.25). Participants were recruited through advertisement on notice boards and emails from unit managers. RESULTS: Thematic analysis revealed five themes but the focus here is on staff judgements which are against the guidelines. Participants indicated that where in their judgement the patient posed no risk and they judged themselves skilled in the procedure, they were justified in deviating from the guidelines. Some staff judgements appeared to be self-protecting, while others were irrational and inconsistent. CONCLUSIONS: Despite use of standard precautions being mandated, staff often deviated from them based on their own assessment of the situation or the patient. Any deviance from the guidelines is of concern but especially so when staff take it upon themselves to apply their own criteria or judgements. These results also suggest there may be some organisational inadequacies with regards to training and supervision of staff.",,"['Bouchoucha, Stephane L', 'Moore, Kathleen A']",,,,
,PMC,What Are the Most Powerful Immunogen Design Vaccine Strategies?: A Structural Biologist’s Perspective,http://dx.doi.org/10.1101/cshperspect.a029470,PMC5666634,,,"The ability of structure-based design to control the shape and reactivity—the atomic-level chemistry—of an immunogen argues for it being one of the “most powerful” immunogen-design strategies. But antigenic reactivity is only one of the properties required to induce a protective immune response. Here, a multidimensional approach is used to exemplify the enabling role atomic-level information can play in the development of immunogens against three viral pathogens, respiratory syncytial virus, influenza A virus, and human immunodeficiency virus (HIV), which have resisted standard approaches to vaccine development. Overall, structure-based strategies incorporating B-cell ontogenies and viral evasion mechanisms appear exceptionally powerful.",,"Kwong, Peter D.",,,,
,PMC,Evidence-Based Options for Controlling Respiratory Virus Transmission,http://dx.doi.org/10.3201/eid2311.171231,PMC5652438,,NO-CC CODE,,2017 Nov,"['Cowling, Benjamin J.', 'Lam, Tommy Tsan-Yuk', 'Yen, Hui-Ling', 'Poon, Leo L.M.', 'Peiris, Malik']",Emerg Infect Dis,,,
,PMC,The expression profile of IFITM family gene in rats,http://dx.doi.org/10.5582/irdr.2017.01066,PMC5735281,,,"The interferon-inducible transmembrane proteins (IFITMs) are a family of small transmembrane proteins belonging to the interferon (IFN)-stimulated gene (ISG) superfamily and strongly induced by IFNs. In this paper, we studied the expression profile of IFITMs in 32 organ tissues. The IFITM mRNA expression profile showed that IFITM1, IFITM2 and IFITM3 were expressed in each tissue, especially, in spermatophore, spermaduct, testicle and epididymis. The expression of IFITM1, IFITM2 and IFITM3 showed a trend from high to low. Except for IFITM3 and IFITM6, the others IFITMs were highly expressed in the bone marrow, and the expression level of them was higher in the tibia than that in other parts of the long bones. In liver, the relative expression of IFITM1 and IFITM3 was higher than that of other members. The expression level of IFITM5 was the highest in bone marrow, successively in pancreas, and it was low in skin, smooth muscle and fat. Interestingly, the expression profile of IFITM2 and IFITM7 in tissues was similar to IFITM5. The expression of IFITM2, IFITM5 and IFITM10 were higher in smooth muscle than that in skeletal muscle. IFITM2, IFITM5, IFITM7 and IFITM10 were both highly expressed in esophagus and trachea. In addition, the expression of IFITM6 in eyes was high, and also in pancreas, gallbladder and bone. In the present study, we systematically analyzed the mRNA expression profile of IFITMs in 32 organ tissues, providing the foundation for the study of the function of the IFITMs.",,"['Lu, Yanqin', 'Zuo, Qingli', 'Zhang, Yao', 'Wang, Yanzhou', 'Li, Tianyou', 'Han, Jinxiang']",,,,
,PMC,Plasma Concentration of Meloxicam in Pediatric Rats,,PMC5710155,,,"In this study, we compared the plasma concentrations of meloxicam in pediatric rat pups (ages: 7, 14, 21, and 28 d) with those of young adult rats. Adult rats received 1.34 mg/kg SC meloxicam to determine the target peak plasma concentration (C(max)) for comparison with the pediatric animals. Pediatric rats received 1.34 mg/kg SC meloxicam, and in all age groups, C(max) met or exceeded that in adults (11.5 ± 2.7 μg/mL). Plasma concentrations were similar between male and female pups within age groups, and peak plasma concentration was achieved more rapidly in rat pups than adults. The analgesic efficacy of this dose was not evaluated in this study.",,"['Pugh, Kristina A', 'Reitnauer, Kyle J', 'Lee, Robyn B', 'Wilkins, William L', 'McDonough, John H', 'Pennington, M Ross', 'Litvin, Samantha R']",,,,
,PMC,Staphylococcus xylosus PCR-validated Decontamination of Murine Individually Ventilated Cage Racks and Air Handling Units by Using ‘Active–Closed’ Exposure to Vaporized Hydrogen Peroxide,,PMC5710153,,,"Vaporized hydrogen peroxide (VHP) is used to decontaminate clinical, biocontainment, and research animal rooms and equipment. To assist with its implementation in a murine facility, we developed a safe and effective method of VHP sterilization of IVC racks and air handling units (AHU). Safety of VHP decontamination was assessed by ensuring VHP levels dissipated to less than 1 ppm in the room prior to personnel reentry and inside the primary enclosure prior to the return of mice; this condition occurred at least 18 h after the VHP cycle. Efficacy of VHP sterilization was assessed by using chemical indicators, biologic indicators, and PCR testing for Staphylococcus xylosus, a commensal organism of murine skin and an opportunistic pathogen, which was present in 160 of 172 (93%) of specimens from occupied IVC racks and the interior surfaces of in-use AHU. Neither mechanized washing nor hand-sanitizing eradicated S. xylosus from equipment airway interiors, with 17% to 24% of specimens remaining PCR-positive for S. xylosus. ‘Static–open’ VHP exposure of sanitized equipment did not ensure its sterilization. In contrast, ‘active–closed’ VHP exposure, in which IVC racks were assembled, sealed, and connected to AHU set to the VHP cycle, increased the proportion of chemical indicators that detected sterilizing levels of VHP inside the assembled equipment, and significantly decreased PCR-detectable S. xylosus inside the equipment. Supplementing bulk steam sterilization of the primary enclosure with VHP sterilization of the secondary housing equipment during room change-outs may help to mitigate opportunistic agents that jeopardize studies involving immunodeficient strains.",,"['Ragland, Natalie H', 'Miedel, Emily L', 'Gomez, Jose M', 'Engelman, Robert W']",,,,
,PMC,Antimicrobial Stewardship Program Using Plan-Do-Study-Act Cycles to Reduce Unjustified Antibiotic Prescribing in Children Admitted With an Asthma Exacerbation,http://dx.doi.org/10.5863/1551-6776-22.6.436,PMC5736256,,,"OBJECTIVE: Antimicrobial stewardship programs (ASPs) ensure appropriate antibiotic use, reduce health care costs, and minimize antibiotic resistance. National asthma guidelines do not recommend antibiotics during an exacerbation unless the child has an infection or comorbidities. The American Academy of Pediatrics (AAP) established a benchmark for unjustified antibiotic use at 6.6%.9 A retrospective study at our institution showed that 7.8% of antibiotics were prescribed without justification in children admitted for asthma. The purpose of this study was to reduce unjustified antibiotic use at our institution by 25% in children through an ASP directed toward asthma. METHODS: The study period lasted from November 2015 to March 2016. Children 6 months to 17 years of age, admitted for an asthma exacerbation, were included while those with comorbidities were excluded. A multidisciplinary team from pediatric pharmacotherapy, pulmonology, emergency department (ED), infectious diseases, and quality improvement was formed to focus on process improvement. Interventions were executed in a series of Plan-Do-Study-Act cycles. In cycle 1, our asthma guidelines on appropriate antibiotic use were disseminated to pediatric house staff and posted in pediatric units. Cycle 2 encompassed presenting the ASP and guidelines to the pediatric ED staff. Cycle 3 consisted of a journal club with the pulmonary division to discuss the role of azithromycin in an asthma exacerbation. RESULTS: In cycle 1, twenty-four patients were reviewed in November 2015. Antibiotics were prescribed in 8/24 (33%) children, with an unjustified rate of 2/24 (8.3%). In cycle 2, twenty-three patients were reviewed in December and January with 8/23 (35%) prescribed antibiotics and an unjustified rate of 2/23 (8.7%). For cycle 3, in February and March 2016, twenty-one children were reviewed. Antibiotics were prescribed in 6/21 (27%) children and all were justified. In total, 68 patients were included in our study and had an unjustified antibiotic prescribing rate of 4/68 (5.9%), a reduction of 25%. CONCLUSION: Our ASP surpassed the benchmark set by AAP guidelines, by reducing the percentage of unjustified antibiotics in children with asthma to 5.9%.",,"['Dorzin, Sasha E.', 'Halaby, Claudia', 'Quintos, Maria Lyn', 'Noor, Asif', 'El-Chaar, Gladys']",,,,
,PMC,Healthcare Provider Knowledge and Attitudes Regarding Reporting Diseases and Events to Public Health Authorities in Tennessee,http://dx.doi.org/10.1097/PHH.0000000000000492,PMC5474221,,,"CONTEXT: In the United States (U.S.), state laws require healthcare providers to report specific diseases and events to public health authorities, a fundamental facet of disease surveillance. However, reporting by providers is often inconsistent, infrequent and delayed. OBJECTIVE: To examine knowledge, attitudes, and practices regarding and understand current barriers to provider disease reporting. DESIGN: A cross-sectional study was conducted via an anonymous, standardized electronic survey. SETTING: The survey was conducted at Vanderbilt University Medical Center, a large, tertiary academic medical center in Nashville, Tennessee. PARTICIPANTS: Healthcare providers in four specialties (internal medicine, pediatrics, obstetrics-gynecology and emergency medicine). MAIN OUTCOME MEASURE(S): Knowledge of and attitudes regarding provider reporting of diseases to public health authorities in Tennessee. RESULTS: The majority of providers acknowledged they cared for patients with reportable diseases (362/435, 83.2%) and believed that it was their responsibility to report to public health authorities (429/436, 98.4%); however less than half had ever reported a case (206/436, 47.2%). The median percent correct on the knowledge assessment of Tennessee reportable diseases and conditions was 81.3% (Interquartile Range [IQR] 68.8–87.5). Providers cited a lack of knowledge of which diseases are reportable (186/429, 43.3%) and the logistics of reporting (153/429, 35.7%) as the primary barriers for compliance. CONCLUSIONS: Most providers acknowledged they cared for patients with reportable diseases and believed they had an obligation to report to public health authorities. However, a lack of knowledge about reporting was frequently described as a limitation to report effectively. Many knowledge deficits were significantly greater among residents than other providers. The policy and practice implications of these findings include a demonstrated need for education of providers about disease reporting as well as development of more convenient reporting mechanisms. Fundamental knowledge of reportable disease requirements and procedures is critical for participation in the broader public health system.",,"['Fill, Mary-Margaret A.', 'Murphree, Rendi', 'Pettit, April C.']",,,,
,PMC,"Knowledge, Attitudes, and Practices Regarding Zika: Paper- and Internet-Based Survey in Zhejiang, China",http://dx.doi.org/10.2196/publichealth.7663,PMC5684512,29084711,CC BY,"BACKGROUND: As public access to the Internet increases, many health workers prefer to carry out health education online, reducing the use of traditional community-based health education methods. Since March 2016, four Zika cases have been confirmed in Zhejiang, China. Rapid assessment of people’s knowledge, attitudes, and practices (KAP) regarding Zika is crucial to its prevention and control. Web-based surveys to assess public KAP may be a growing trend; however, we had little experience with this method. OBJECTIVES: The aim of this study was to explore KAP regarding Zika in residents of Zhejiang using both traditional paper- and innovative Internet-based investigations. METHODS: A questionnaire was designed by Zhejiang Provincial Center for Disease Control and Prevention. A paper-based version of the survey was used in a cross-sectional community study following multistage cluster random sampling, and an Internet-based survey was promoted through a local health education site. Data were interpreted via univariate and multivariate analyses. RESULTS: A total of 447 community residents participated in the paper-based survey, with a response rate of 89.4% (447/500), and 621 eligible Internet users participated in the Internet-based survey, with a response rate of 36.92% (621/1682). Age, education level, and occupation differed significantly between participants in the paper- and Internet-based surveys. Participants completing the Internet-based survey were much younger (χ(2)(2)=144.7, P<.001) and had a higher level of education (χ(2)(2)=423.5, P<.001) than those completing the paper-based survey. Among participants completing the paper-based survey, there were more farmers, housewives, and unemployed people (χ(2)(3)=413.7, P<.001). Overall, 83.52% of participants (892/1068) knew the transmission route for Zika, 76.12% (813/1068) knew that pregnant women were at high risk of severe complications, 66.39% (709/1068) knew that contracting Zika during pregnancy could lead to newborn babies with microcephaly, and 98.88% (1056/1068) knew places where mosquitos could usually be found. After controlling for sociodemographic variables, participants completing the Internet-based survey were more likely to know the transmission route of Zika (odds ratio [OR]=5.0, 95% CI 3.0-8.0), the association between pregnant women with Zika and newborn babies with microcephaly (OR 2.1, 95% CI 1.4-3.0), and that pregnant women were at high risk for Zika (OR 5.5, 95% CI 3.5-8.4) than those completing the paper-based survey. They were less likely to worry about contracting Zika (OR 0.6, 95% CI 0.4-0.9) and more likely to actively seek information about Zika than participants completing the paper-based survey (OR 3.3, 95% CI 2.0-5.6). CONCLUSIONS: Participants completing the Internet-based survey had a higher level of basic knowledge and more positive attitudes and behaviors than participants completing the paper-based survey. In addition to providing Web-based health information, the government should ensure sufficient access to health information for the elderly and less educated people in the community to improve health equity.",2017 Oct 30,"['Huang, Yu', 'Xu, Shuiyang', 'Wang, Lei', 'Zhao, Yushui', 'Liu, He', 'Yao, Dingming', 'Xu, Yue', 'Lv, Qiaohong', 'Hao, Gang', 'Xu, Yan', 'Wu, Qingqing']",JMIR Public Health Surveill,,,
,PMC,Murine Olfactory Bulb Interneurons Survive Infection with a Neurotropic Coronavirus,http://dx.doi.org/10.1128/JVI.01099-17,PMC5660484,,,"Viral infection of the central nervous system (CNS) is complicated by the mostly irreplaceable nature of neurons, as the loss of neurons has the potential to result in permanent damage to brain function. However, whether neurons or other cells in the CNS sometimes survive infection and the effects of infection on neuronal function is largely unknown. To address this question, we used the rJHM strain (rJ) of mouse hepatitis virus (MHV), a neurotropic coronavirus that causes acute encephalitis in susceptible strains of mice. To determine whether neurons or other CNS cells survive acute infection with this virulent virus, we developed a recombinant JHMV that expresses Cre recombinase (rJ-Cre) and infected mice that universally expressed a silent (floxed) version of tdTomato. Infection of these mice with rJ-Cre resulted in expression of tdTomato in host cells. The results showed that some cells were able to survive the infection, as demonstrated by continued tdTomato expression after virus antigen could no longer be detected. Most notably, interneurons in the olfactory bulb, which are known to be inhibitory, represented a large fraction of the surviving cells. In conclusion, our results indicated that some neurons are resistant to virus-mediated cell death and provide a framework for studying the effects of prior coronavirus infection on neuron function. IMPORTANCE We developed a novel recombinant virus that allows the study of cells that survive an infection by a central nervous system-specific strain of murine coronavirus. Using this virus, we identified neurons and, to a lesser extent, nonneuronal cells in the brain that were infected during the acute phase of the infection and survived for approximately 2 weeks until the mice succumbed to the infection. We focused on neurons and glial cells within the olfactory bulb because the virus enters the brain at this site. Our results show that interneurons of the olfactory bulb were the primary cell type able to survive infection. Further, these results indicate that this system will be useful for functional and gene expression studies of cells in the brain that survive acute infection.",,"['Wheeler, D. Lori', 'Athmer, Jeremiah', 'Meyerholz, David K.', 'Perlman, Stanley']",,,,
,PMC,Autophagy and the unfolded protein response promote profibrotic effects of TGF-β(1) in human lung fibroblasts,http://dx.doi.org/10.1152/ajplung.00372.2017,PMC5900356,,,"Idiopathic pulmonary fibrosis (IPF) is a lethal fibrotic lung disease in adults with limited treatment options. Autophagy and the unfolded protein response (UPR), fundamental processes induced by cell stress, are dysregulated in lung fibroblasts and epithelial cells from humans with IPF. Human primary cultured lung parenchymal and airway fibroblasts from non-IPF and IPF donors were stimulated with transforming growth factor-β(1) (TGF-β(1)) with or without inhibitors of autophagy or UPR (IRE1 inhibitor). Using immunoblotting, we monitored temporal changes in abundance of protein markers of autophagy (LC3βII and Atg5-12), UPR (BIP, IRE1α, and cleaved XBP1), and fibrosis (collagen 1α2 and fibronectin). Using fluorescent immunohistochemistry, we profiled autophagy (LC3βII) and UPR (BIP and XBP1) markers in human non-IPF and IPF lung tissue. TGF-β(1)-induced collagen 1α2 and fibronectin protein production was significantly higher in IPF lung fibroblasts compared with lung and airway fibroblasts from non-IPF donors. TGF-β(1) induced the accumulation of LC3βII in parallel with collagen 1α2 and fibronectin, but autophagy marker content was significantly lower in lung fibroblasts from IPF subjects. TGF-β(1)-induced collagen and fibronectin biosynthesis was significantly reduced by inhibiting autophagy flux in fibroblasts from the lungs of non-IPF and IPF donors. Conversely, only in lung fibroblasts from IPF donors did TGF-β(1) induce UPR markers. Treatment with an IRE1 inhibitor decreased TGF-β1-induced collagen 1α2 and fibronectin biosynthesis in IPF lung fibroblasts but not those from non-IPF donors. The IRE1 arm of the UPR response is uniquely induced by TGF-β(1) in lung fibroblasts from human IPF donors and is required for excessive biosynthesis of collagen and fibronectin in these cells.",,"['Ghavami, Saeid', 'Yeganeh, Behzad', 'Zeki, Amir A.', 'Shojaei, Shahla', 'Kenyon, Nicholas J.', 'Ott, Sean', 'Samali, Afshin', 'Patterson, John', 'Alizadeh, Javad', 'Moghadam, Adel Rezaei', 'Dixon, Ian M. C.', 'Unruh, Helmut', 'Knight, Darryl A.', 'Post, Martin', 'Klonisch, Thomas', 'Halayko, Andrew J.']",,,,
,PMC,Detection of Respiratory Viruses from ARTI Patients by xTAG RVP Fast v2 Assay and Conventional Methods,http://dx.doi.org/10.21315/mjms2017.24.5.4,PMC5772813,,,"INTRODUCTION: Acute respiratory tract infections (ARTIs) are a major cause of morbidity and mortality in paediatric patients. Therefore, early detection of the viral aetiologies of ARTIs is essential for patient management and infection control. In this study, we evaluated the performance of a new multiplex polymerase chain reaction (PCR) assay (xTAG Respiratory Viral Panel [RVP] Fast v2) in the detection of respiratory viruses by comparing it with that of viral culture and direct immunofluorescence (IF) staining. METHODS: Nasopharyngeal swab and aspirate samples were collected prospectively from 199 patients who presented with ARTIs at the University Malaya Medical Centre (UMMC) in Kuala Lumpur, Malaysia during a 10-month period. The PCR assay was conducted in parallel with conventional culture and direct IF staining methods. RESULTS: The positive rate of the xTAG RVP Fast v2 assay (78.4%) in detecting respiratory viruses was higher than that of the viral isolation (7.5%) and direct IF (23.1%) methods. Using the xTAG RVP Fast v2 assay, human enterovirus/human rhinovirus (HEV/HRV) was the most frequently detected (46.2%). The xTAG RVP Fast v2 assay revealed mixed infection caused by two or three respiratory viruses in 40 specimens, and these were undetected by the viral isolation and direct IF methods. CONCLUSION: The xTAG RVP Fast v2 assay was superior to conventional methods in the identification of common respiratory viruses, with higher sensitivity and shorter turnaround times for laboratory results.",,"['Kuan, Chee Sian', 'Yew, Su Mei', 'Hooi, Poh Sim', 'Lee, Lu Mei', 'Ng, Kee Peng']",,,,
,PMC,Expression profile and promoter analysis of HEPIS,http://dx.doi.org/10.3892/etm.2017.5374,PMC5763650,,,"Human embryo lung cellular protein interacting with severe acute respiratory syndrome-coronavirus nonstructural protein-10 (HEPIS) is a novel transcriptional repressor, the expression profile and promoter activity of which have not been well studied. In the present study, in situ hybridization of RNA was used to study differential HEPIS expression levels in different types of cancer and normal tissues. A total of six truncated lengths of the HEPIS promoter regulatory sequences were cloned into the pGL3-basic vector, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and dual luciferase reporter assays were performed. The results of RT-qPCR demonstrated that HEPIS expression levels differed across four breast cancer cell lines. The results of the dual luciferase reporter assays revealed that the activities of the reporter gene fragments spanning −1334/+373, −1203/+373, −1060/+373 and −899/+373 bp were higher compared with the reporter gene fragments spanning −759/+373 and −279/+373 bp. A search of the transcription factor database TRANSFAC identified numerous octamer transcription factor-1 (OCT-1), nuclear factor (NF)-κB and C-JUN transcription factor binding sites located on the HEPIS promoter (pHEPIS). Furthermore, the results revealed that mutations of the OCT-1 (−1236/−1223 bp), NF-κB (−1186/−1176 bp) and C-JUN (−856/−846 bp) sites on the human pHEPIS resulted in a decrease in luciferase activity. A chromatin immunoprecipitation assay revealed that OCT-1, NF-κB and C-JUN bound to pHEPIS in a site-dependent manner at the basal state. The TRANSFAC database was used to analyze the pHEPIS of multiple species and several activator protein-1, NF-κB and OCT-1 transcription factor binding sites were predicted. In conclusion, the results of the present study suggest that HEPIS is expressed at different levels in multiple organs and breast cancer cell lines. Furthermore, these findings indicate that OCT-1, NF-κB and C-JUN transcription factors are associated with transcriptional regulation of the HEPIS gene.",,"['Hu, Fen', 'Zhang, Yunfeng']",,,,
,PMC,CD59 association with infectious bronchitis virus particles protects against antibody-dependent complement-mediated lysis,http://dx.doi.org/10.1099/jgv.0.000962,PMC5845662,,,"CD59 protein functions as a negative regulator of the terminal pathway of the complement system by binding to the C8/C9 factors. To date, little is known about the role of CD59 in coronavirus infectious bronchitis virus (IBV) infection. In this study, we discovered that CD59 was downregulated in IBV-infected cells and was associated with IBV virions. This association protected IBV particles from antibody-dependent complement-mediated lysis. IBV titres in the supernatant were significantly increased when CD59 proteins were overexpressed in cells followed by IBV infection, and this observation was further supported by knockdown or cleavage of CD59. Because no considerable change in IBV N protein and viral RNA levels was detected in total cell lysates prepared from the overexpression, knockdown or cleavage of CD59 groups, our data indicated that CD59 was involved in IBV particle release and that IBV had evolved a mechanism to utilize CD59 to evade complement-mediated destruction.",,"['Wei, Yanquan', 'Ji, Yanhong', 'Guo, Huichen', 'Zhi, Xiaoying', 'Han, Shichong', 'Zhang, Yun', 'Gao, Yuan', 'Chang, Yanyan', 'Yan, Dan', 'Li, Kangyu', 'Liu, Ding Xiang', 'Sun, Shiqi']",,,,
,PMC,The bulky and the sweet: How neutralizing antibodies and glycan receptors compete for virus binding,http://dx.doi.org/10.1002/pro.3319,PMC5699497,,,"Numerous viruses rely on glycan receptor binding as the initial step in host cell infection. Engagement of specific glycan receptors such as sialylated carbohydrates, glycosaminoglycans, or histo‐blood group antigens can determine host range, tissue tropism, and pathogenicity. Glycan receptor‐binding sites are typically located in exposed regions on viral surfaces—sites that are also generally prone to binding of neutralizing antibodies that directly interfere with virus‐glycan receptor interactions. In this review, we examine the locations and architecture of the glycan‐ and antibody‐binding sites in four different viruses with stalk‐like attachment proteins (reovirus, influenza virus, norovirus, and coronavirus) and investigate the mechanisms by which antibodies block glycan recognition. Those viruses exemplify that direct molecular mimicking of glycan receptors by antibodies is rare and further demonstrate that antibodies often partly overlap or bind sufficiently close to the receptor‐binding region to hinder access to this site, achieving neutralization partially because of the epitope location and partly due to their sheer size.",,"['Dietrich, Melanie H.', 'Harprecht, Christina', 'Stehle, Thilo']",,,,
,PMC,Recent advances in the development of antiviral therapeutics for Rift Valley fever virus infection,http://dx.doi.org/10.2217/fvl-2017-0060,PMC5696620,,,"Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus endemic to sub-Saharan Africa and the Arabian Peninsula and the etiological agent of Rift Valley fever. Rift Valley fever is a disease of major public health and economic concern, affecting livestock and humans. In ruminants, RVFV infection is characterized by high mortality rates in newborns and near 100% abortion rates in pregnant animals. Infection in humans is typically manifested as a self-limiting febrile illness, but can lead to severe and fatal hepatitis, encephalitis, hemorrhagic fever or retinitis with partial or complete blindness. Currently, there are no specific treatment options available for RVFV infection. This review presents a summary of the therapeutic approaches that have been explored on the treatment of RVFV infection.",,"['Atkins, Colm', 'Freiberg, Alexander N']",,,,
,PMC,Clinical relevance of peroxisome proliferator‐activated receptor‐γ gene polymorphisms with sepsis,http://dx.doi.org/10.1002/jcla.22340,PMC6817069,,,"BACKGROUND: Peroxisome proliferator‐activated receptor‐γ (PPARγ) is a regulator of inflammation. This study aimed to explore associations between PPARγ gene single‐nucleotide polymorphisms (SNPs) and susceptibility to and clinical outcome of sepsis in the North China Han population. METHODS: This study included 303 patients with sepsis and 303 controls. We conducted genetic typing for 13 common PPARγ gene SNPs (improved multiplex ligation detection reaction), linkage disequilibrium mapping, and haplotype inference. Associations between SNP genotypes/haplotypes and sepsis susceptibility and outcome (septic shock, organ dysfunction, or death) were assessed using unconditional logistic regression analysis. RESULTS: For rs2972164, patients with genotypes CT/CT+TT had higher risk of sepsis than genotype CC (odds ratio [95% CI]: 1.74 [1.05‐2.86], P = .03 and 1.72 [1.06‐2.80], P = .026, respectively); the T allele was associated with increased sepsis risk compared with the C allele (1.64 [1.04‐2.58], P = .033). For rs1801282, genotypes CG/CG+GG had lower risk of sepsis than genotype CC (0.55 [0.33‐0.92], P = .024 and 0.57 [0.35‐0.95], P = .03, respectively); the G allele was associated with decreased sepsis risk compared with the C allele (0.62 [0.39‐1.01], P = .055). For rs4135275, genotypes AG/AG+GG had higher risk of severe organ dysfunction (multiple organ dysfunction syndrome score >8) than genotype AA (2.66 [1.16‐6.09], P = .038 and 2.21 [1.00‐4.85], P = .042, respectively). Haplotype TAT (rs2972164, rs4684846, and rs17036188) was associated with increased sepsis risk (1.66 [1.03‐2.67], P = .038). CONCLUSIONS: No mutation was correlated with septic shock or death. PPARγ gene polymorphisms may play a role in the occurrence and progression of sepsis in the North China Han population.",,"['Liu, Yu', 'Wan, Wenhui', 'Fang, Fang', 'Guo, Lei', 'Zhao, Yusheng', 'Zhang, Xinghu', 'Huang, Fang']",,,,
,PMC,Structure-guided development of a potent and selective noncovalent active site inhibitor of USP7,http://dx.doi.org/10.1016/j.chembiol.2017.09.003,PMC5749250,,,"Deubiquitinating enzymes (DUBs) have garnered significant attention as drug targets in the last 5–10 years. The excitement stems in large part from the powerful ability of DUB inhibitors to promote degradation of oncogenic proteins, especially proteins that are challenging to directly target but which are stabilized by DUB family members. Highly-optimized and well-characterized DUB inhibitors have thus become highly sought after tools. Most reported DUB inhibitors, however, are polypharmacological agents possessing weak (micromolar) potency toward their primary target, limiting their utility in target validation and mechanism studies. Due to a lack of high resolution DUB•small molecule ligand complex structures, no structure-guided optimization efforts have been reported for a mammalian DUB. Here, we report a small molecule•ubiquitin specific protease (USP) family DUB co-structure and rapid design of potent and selective inhibitors of USP7 guided by the structure. Interestingly, the compounds are noncovalent active site inhibitors.",,"['Lamberto, Ilaria', 'Liu, Xiaoxi', 'Seo, Hyuk-Soo', 'Schauer, Nathan J', 'Iacob, Roxana E', 'Hu, Wanyi', 'Das, Deepika', 'Mikhailova, Tatiana', 'Weisberg, Ellen L', 'Engen, John R', 'Anderson, Kenneth C', 'Chauhan, Dharminder', 'Dhe-Paganon, Sirano', 'Buhrlage, Sara J']",,,,
,PMC,The SARS-CoV Fusion Peptide forms an Extended Bipartite Fusion Platform that Perturbs Membrane Order in a Calcium-Dependent Manner,http://dx.doi.org/10.1016/j.jmb.2017.10.017,PMC5705393,,,"Coronaviruses are a major infectious disease threat, and include the pathogenic human pathogens of zoonotic origin: SARS-CoV and MERS-CoV. Entry of coronaviruses into host cells is mediated by the viral spike (S) protein, which is structurally categorized as a class I viral fusion protein, within the same group as influenza virus and HIV. However, S proteins have two distinct cleavage sites that can be activated by a much wider range of proteases. The exact location of the coronavirus fusion peptide (FP) has been disputed. However, most evidence suggests that the domain immediately downstream of the S2′ cleavage site is the FP (amino acids 798-818 SFIEDLLFNKVTLADAGFMKQY for SARS-CoV, FP1). In our previous ESR spectroscopic studies, the membrane ordering effect of influenza virus, HIV and Dengue virus FPs have been consistently observed. In this study, we used this effect as a criterion to identify and characterize the bona fide SARS-CoV FP. Our results indicate that both FP1 and the region immediately downstream (amino acids 816-835 KQYGECLGDINARDLICAQKF, FP2) induce significant membrane ordering. Furthermore, their effects are calcium-dependent, which is consistent with in vivo data showing that calcium is required for SARS-CoV S-mediated fusion. Isothermal titration calorimetry showed a direct interaction between calcium cations and both FPs. This Ca(2+)-dependency membrane ordering was not observed with influenza FP, indicating that the coronavirus FP exhibits a mechanistically different behavior. Membrane ordering effects are greater and penetrate deeper into membranes when FP1 and FP2 act in a concerted manner, suggesting that they form an extended fusion “platform”.",,"['Lai, Alex L.', 'Millet, Jean K.', 'Daniel, Susan', 'Freed, Jack H.', 'Whittaker, Gary R.']",,,,
,PMC,Carbapenemase-Producing Organisms: A Global Scourge,http://dx.doi.org/10.1093/cid/cix893,PMC5884739,,,"The dramatic increase in the prevalence and clinical impact of infections caused by bacteria producing carbapenemases is a global health concern. Carbapenemase production is especially problematic when encountered in members of the family Enterobacteriaceae. Due to their ability to readily spread and colonize patients in healthcare environments, preventing the transmission of these organisms is a major public health initiative and coordinated international effort are needed. Central to the treatment and control of carbapenemase-producing organisms (CPOs) are phenotypic (growth-/biochemical-dependent) and nucleic acid–based carbapenemase detection tests that identify carbapenemase activity directly or their associated molecular determinants. Importantly, bacterial isolates harboring carbapenemases are often resistant to multiple antibiotic classes, resulting in limited therapy options. Emerging agents, novel antibiotic combinations and treatment regimens offer promise for management of these infections. This review highlights our current understanding of CPOs with emphasis on their epidemiology, detection, treatment, and control.",,"['Bonomo, Robert A', 'Burd, Eileen M', 'Conly, John', 'Limbago, Brandi M', 'Poirel, Laurent', 'Segre, Julie A', 'Westblade, Lars F']",,,,
,PMC,"Nosocomial amplification of MERS-coronavirus in South Korea, 2015",http://dx.doi.org/10.1093/trstmh/trx046,PMC6257029,,,"BACKGROUND: Nosocomial amplification resulted in nearly 200 cases of Middle East respiratory syndrome (MERS) during the 2015 South Korean MERS-coronavirus outbreak. It remains unclear whether certain types of cases were more likely to cause secondary infections than others, and if so, why. METHODS: Publicly available demographic and transmission network data for all cases were collected from the Ministry of Health and Welfare. Statistical analyses were conducted to determine the relationship between demographic characteristics and the likelihood of human-to-human transmission. Findings from the statistical analyses were used to inform a hypothesis-directed literature review, through which mechanistic explanations for nosocomial amplification were developed. RESULTS: Cases that failed to recover from MERS were more likely to cause secondary infections than those that did. Increased probability of direct, human-to-human transmission due to clinical manifestations associated with death, as well as indirect transmission via environmental contamination (e.g., fomites and indoor ventilation systems), may serve as mechanistic explanations for nosocomial amplification of MERS-coronavirus in South Korea. CONCLUSIONS: In addition to closely monitoring contacts of MERS cases that fail to recover during future nosocomial outbreaks, potential fomites with which they may have had contact should be sanitized. Furthermore, indoor ventilation systems that minimize recirculation of pathogen-bearing droplets should be implemented whenever possible.",,"['Majumder, Maimuna S', 'Brownstein, John S', 'Finkelstein, Stan N', 'Larson, Richard C', 'Bourouiba, Lydia']",,,,
,PMC,Epidemiology of clinical feline herpesvirus infection in zoo-housed cheetahs (Acinonyx jubatus),http://dx.doi.org/10.2460/javma.251.8.946,PMC6369687,,,"OBJECTIVE: To determine the incidence of and risk factors for clinical feline herpesvirus (FHV) infection in zoo-housed cheetahs and determine whether dam infection was associated with offspring infection. DESIGN: Retrospective cohort study. ANIMALS: 144 cheetah cubs born in 6 zoos from 1988 through 2007. PROCEDURES: Data were extracted from the health records of cheetahs and their dams to identify incident cases of clinical FHV infection and estimate incidence from birth to 18 months of age. Univariate and multivariable Cox proportional hazards models, controlling for correlations among cheetahs with the same dam, were used to identify risk factors for incident FHV infection. RESULTS: Cumulative incidence of FHV infection in cheetah cubs was 35% (50/144). No significant association between dam and offspring infection was identified in any model. Factors identified as significant through multivariable analysis varied by age group. For cheetahs up to 3 months of age, the most important predictor of FHV infection was having a dam that had received a preparturition FHV vaccine regimen that included a modified-live virus vaccine versus a dam that had received no preparturition vaccine. Other risk factors included being from a small litter, being born to a primiparous dam, and male sex. CONCLUSIONS AND CLINICAL RELEVANCE: This study provided the first population-level characterization of the incidence of and risk factors for FHV infection in cheetahs, and findings confirmed the importance of this disease. Recognition that clinical FHV infection in the dam was not a significant predictor of disease in cubs and identification of other significant factors have implications for disease management.",,"['Witte, Carmel L.', 'Lamberski, Nadine', 'Rideout, Bruce A.', 'Vaida, Florin', 'Citino, Scott B.', 'Barrie, Michael T.', 'Haefele, Holly J.', 'Junge, Randall E.', 'Murray, Suzan', 'Hungerford, Laura L.']",,,,
,PMC,Nidovirus-Associated Proliferative Pneumonia in the Green Tree Python (Morelia viridis),http://dx.doi.org/10.1128/JVI.00718-17,PMC5640870,,,"In 2014 we observed a noticeable increase in the number of sudden deaths among green tree pythons (Morelia viridis). Pathological examination revealed the accumulation of mucoid material within the airways and lungs in association with enlargement of the entire lung. We performed a full necropsy and histological examination on 12 affected green tree pythons from 7 different breeders to characterize the pathogenesis of this mucinous pneumonia. By histology we could show a marked hyperplasia of the airway epithelium and of faveolar type II pneumocytes. Since routine microbiological tests failed to identify a causative agent, we studied lung tissue samples from a few diseased snakes by next-generation sequencing (NGS). From the NGS data we could assemble a piece of RNA genome whose sequence was <85% identical to that of nidoviruses previously identified in ball pythons and Indian pythons. We then employed reverse transcription-PCR to demonstrate the presence of the novel nidovirus in all diseased snakes. To attempt virus isolation, we established primary cultures of Morelia viridis liver and brain cells, which we inoculated with homogenates of lung tissue from infected individuals. Ultrastructural examination of concentrated cell culture supernatants showed the presence of nidovirus particles, and subsequent NGS analysis yielded the full genome of the novel virus Morelia viridis nidovirus (MVNV). We then generated an antibody against MVNV nucleoprotein, which we used alongside RNA in situ hybridization to demonstrate viral antigen and RNA in the affected lungs. This suggests that in natural infection MVNV damages the respiratory tract epithelium, which then results in epithelial hyperplasia, most likely as an exaggerated regenerative attempt in association with increased epithelial turnover. IMPORTANCE Novel nidoviruses associated with severe respiratory disease were fairly recently identified in ball pythons and Indian pythons. Herein we report on the isolation and identification of a further nidovirus from green tree pythons (Morelia viridis) with fatal pneumonia. We thoroughly characterized the pathological changes in the infected individuals and show that nidovirus infection is associated with marked epithelial proliferation in the respiratory tract. We speculate that this and the associated excess mucus production can lead to the animals' death by inhibiting normal gas exchange in the lungs. The virus was predominantly detected in the respiratory tract, which renders transmission via the respiratory route likely. Nidoviruses cause sudden outbreaks with high rates of mortality in breeding collections, and most affected snakes die without prior clinical signs. These findings, together with those of other groups, indicate that nidoviruses are a likely cause of severe pneumonia in pythons.",,"['Dervas, Eva', 'Hepojoki, Jussi', 'Laimbacher, Andrea', 'Romero-Palomo, Fernando', 'Jelinek, Christine', 'Keller, Saskia', 'Smura, Teemu', 'Hepojoki, Satu', 'Kipar, Anja', 'Hetzel, Udo']",,,,
,PMC,Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase,http://dx.doi.org/10.1128/JVI.00754-17,PMC5640865,,,"Hepatitis E virus (HEV) causes an acute, self-limiting hepatitis in healthy individuals and leads to chronic disease in immunocompromised individuals. HEV infection in pregnant women results in a more severe outcome, with the mortality rate going up to 30%. Though the virus usually causes sporadic infection, epidemics have been reported in developing and resource-starved countries. No specific antiviral exists against HEV. A combination of interferon and ribavirin therapy has been used to control the disease with some success. Zinc is an essential micronutrient that plays crucial roles in multiple cellular processes. Zinc salts are known to be effective in reducing infections caused by few viruses. Here, we investigated the effect of zinc salts on HEV replication. In a human hepatoma cell (Huh7) culture model, zinc salts inhibited the replication of genotype 1 (g-1) and g-3 HEV replicons and g-1 HEV infectious genomic RNA in a dose-dependent manner. Analysis of a replication-defective mutant of g-1 HEV genomic RNA under similar conditions ruled out the possibility of zinc salts acting on replication-independent processes. An ORF4-Huh7 cell line-based infection model of g-1 HEV further confirmed the above observations. Zinc salts did not show any effect on the entry of g-1 HEV into the host cell. Furthermore, our data reveal that zinc salts directly inhibit the activity of viral RNA-dependent RNA polymerase (RdRp), leading to inhibition of viral replication. Taken together, these studies unravel the ability of zinc salts in inhibiting HEV replication, suggesting their possible therapeutic value in controlling HEV infection. IMPORTANCE Hepatitis E virus (HEV) is a public health concern in resource-starved countries due to frequent outbreaks. It is also emerging as a health concern in developed countries owing to its ability to cause acute and chronic infection in organ transplant and immunocompromised individuals. Although antivirals such as ribavirin have been used to treat HEV cases, there are known side effects and limitations of such therapy. Our discovery of the ability of zinc salts to block HEV replication by virtue of their ability to inhibit the activity of viral RdRp is important because these findings pave the way to test the efficacy of zinc supplementation therapy in HEV-infected patients. Since zinc supplementation therapy is known to be safe in healthy individuals and since high-dose zinc is used in the treatment of Wilson's disease, it may be possible to control HEV-associated health problems following a similar treatment regimen.",,"['Kaushik, Nidhi', 'Subramani, Chandru', 'Anang, Saumya', 'Muthumohan, Rajagopalan', 'Shalimar,', 'Nayak, Baibaswata', 'Ranjith-Kumar, C. T.', 'Surjit, Milan']",,,,
,PMC,Nipah and Hendra Virus Nucleoproteins Inhibit Nuclear Accumulation of Signal Transducer and Activator of Transcription 1 (STAT1) and STAT2 by Interfering with Their Complex Formation,http://dx.doi.org/10.1128/JVI.01136-17,PMC5640859,,,"Henipaviruses, such as Nipah (NiV) and Hendra (HeV) viruses, are highly pathogenic zoonotic agents within the Paramyxoviridae family. The phosphoprotein (P) gene products of the paramyxoviruses have been well characterized for their interferon (IFN) antagonist activity and their contribution to viral pathogenicity. In this study, we demonstrated that the nucleoprotein (N) of henipaviruses also prevents the host IFN signaling response. Reporter assays demonstrated that the NiV and HeV N proteins (NiV-N and HeV-N, respectively) dose-dependently suppressed both type I and type II IFN responses and that the inhibitory effect was mediated by their core domains. Additionally, NiV-N prevented the nuclear transport of signal transducer and activator of transcription 1 (STAT1) and STAT2. However, NiV-N did not associate with Impα5, Impβ1, or Ran, which are members of the nuclear transport system for STATs. Although P protein is known as a binding partner of N protein and actively retains N protein in the cytoplasm, the IFN antagonist activity of N protein was not abolished by the coexpression of P protein. This suggests that the IFN inhibition by N protein occurs in the cytoplasm. Furthermore, we demonstrated that the complex formation of STATs was hampered in the N protein-expressing cells. As a result, STAT nuclear accumulation was reduced, causing a subsequent downregulation of interferon-stimulated genes (ISGs) due to low promoter occupancy by STAT complexes. This novel route for preventing host IFN responses by henipavirus N proteins provides new insight into the pathogenesis of these viruses. IMPORTANCE Paramyxoviruses are well known for suppressing interferon (IFN)-mediated innate immunity with their phosphoprotein (P) gene products, and the henipaviruses also possess P, V, W, and C proteins for evading host antiviral responses. There are numerous studies providing evidence for the relationship between viral pathogenicity and antagonistic activities against IFN responses by P gene products. Meanwhile, little attention has been paid to the influence of nucleoprotein (N) on host innate immune responses. In this study, we demonstrated that both the NiV and HeV N proteins have antagonistic activity against the JAK/STAT signaling pathway by preventing the nucleocytoplasmic trafficking of STAT1 and STAT2. This inhibitory effect is due to an impairment of the ability of STATs to form complexes. These results provide new insight into the involvement of N protein in viral pathogenicity via its IFN antagonism.",,"['Sugai, Akihiro', 'Sato, Hiroki', 'Takayama, Ikuyo', 'Yoneda, Misako', 'Kai, Chieko']",,,,
,PMC,[(18)F]-Fluorodeoxyglucose Uptake in Lymphoid Tissue Serves as a Predictor of Disease Outcome in the Nonhuman Primate Model of Monkeypox Virus Infection,http://dx.doi.org/10.1128/JVI.00897-17,PMC5640857,,,"Real-time bioimaging of infectious disease processes may aid countermeasure development and lead to an improved understanding of pathogenesis. However, few studies have identified biomarkers for monitoring infections using in vivo imaging. Previously, we demonstrated that positron emission tomography/computed tomography (PET/CT) imaging with [(18)F]-fluorodeoxyglucose (FDG) can monitor monkeypox disease progression in vivo in nonhuman primates (NHPs). In this study, we investigated [(18)F]-FDG-PET/CT imaging of immune processes in lymphoid tissues to identify patterns of inflammation in the monkepox NHP model and to determine the value of [(18)F]-FDG-PET/CT as a biomarker for disease and treatment outcomes. Quantitative analysis of [(18)F]-FDG-PET/CT images revealed differences between moribund and surviving animals at two sites vital to the immune response to viral infections, bone marrow and lymph nodes (LNs). Moribund NHPs demonstrated increased [(18)F]-FDG uptake in bone marrow 4 days postinfection compared to surviving NHPs. In surviving, treated NHPs, increase in LN volume correlated with [(18)F]-FDG uptake and peaked 10 days postinfection, while minimal lymphadenopathy and higher glycolytic activity were observed in moribund NHPs early in infection. Imaging data were supported by standard virology, pathology, and immunology findings. Even with the limited number of subjects, imaging was able to differentiate the difference between disease outcomes, warranting additional studies to demonstrate whether [(18)F]-FDG-PET/CT can identify other, subtler effects. Visualizing altered metabolic activity at sites involved in the immune response by [(18)F]-FDG-PET/CT imaging is a powerful tool for identifying key disease-specific time points and locations that are most relevant for pathogenesis and treatment. IMPORTANCE Positron emission tomography and computed tomography (PET/CT) imaging is a universal tool in oncology and neuroscience. The application of this technology to infectious diseases is far less developed. We used PET/CT imaging with [(18)F]-labeled fluorodeoxyglucose ([(18)F]-FDG) in monkeys after monkeypox virus exposure to monitor the immune response in lymphoid tissues. In lymph nodes of surviving monkeys, changes in [(18)F]-FDG uptake positively correlated with enlargement of the lymph nodes and peaked on day 10 postinfection. In contrast, the bone marrow and lymph nodes of nonsurvivors showed increased [(18)F]-FDG uptake by day 4 postinfection with minimal lymph node enlargement, indicating that elevated cell metabolic activity early after infection is predictive of disease outcome. [(18)F]-FDG-PET/CT imaging can provide real-time snapshots of metabolic activity changes in response to viral infections and identify key time points and locations most relevant for monitoring the development of pathogenesis and for potential treatment to be effective.",,"['Dyall, Julie', 'Johnson, Reed F.', 'Chefer, Svetlana', 'Leyson, Christopher', 'Thomasson, David', 'Seidel, Jurgen', 'Ragland, Dan R.', 'Byrum, Russell', 'Jett, Catherine', 'Cann, Jennifer A.', 'St. Claire, Marisa', 'Jagoda, Elaine', 'Reba, Richard C.', 'Hammoud, Dima', 'Blaney, Joseph E.', 'Jahrling, Peter B.']",,,,
,PMC,Persistent Transmissible Gastroenteritis Virus Infection Enhances Enterotoxigenic Escherichia coli K88 Adhesion by Promoting Epithelial-Mesenchymal Transition in Intestinal Epithelial Cells,http://dx.doi.org/10.1128/JVI.01256-17,PMC5640843,,,"Transmissible gastroenteritis virus (TGEV) is a coronavirus characterized by diarrhea and high morbidity rates, and the mortality rate is 100% in piglets less than 2 weeks old. Pigs infected with TGEV often suffer secondary infection by other pathogens, which aggravates the severity of diarrhea, but the mechanisms remain unknown. Here, we hypothesized that persistent TGEV infection stimulates the epithelial-mesenchymal transition (EMT), and thus enterotoxigenic Escherichia coli (ETEC) can more easily adhere to generating cells. Intestinal epithelial cells are the primary targets of TGEV and ETEC infections. We found that TGEV can persistently infect porcine intestinal columnar epithelial cells (IPEC-J2) and cause EMT, consistent with multiple changes in key cell characteristics. Infected cells display fibroblast-like shapes; exhibit increases in levels of mesenchymal markers with a corresponding loss of epithelial markers; have enhanced expression levels of interleukin-1β (IL-1β), IL-6, IL-8, transforming growth factor β (TGF-β), and tumor necrosis factor alpha (TNF-α) mRNAs; and demonstrate increases in migratory and invasive behaviors. Additional experiments showed that the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) signaling pathways via TGF-β is critical for the TGEV-mediated EMT process. Cellular uptake is also modified in cells that have undergone EMT. TGEV-infected cells have higher levels of integrin α5 and fibronectin and exhibit enhanced ETEC K88 adhesion. Reversal of EMT reduces ETEC K88 adhesion and inhibits the expression of integrin α5 and fibronectin. Overall, these results suggest that TGEV infection induces EMT in IPEC-J2 cells, increasing the adhesion of ETEC K88 in the intestine and facilitating dual infection. IMPORTANCE Transmissible gastroenteritis virus (TGEV) causes pig diarrhea and is often followed by secondary infection by other pathogens. In this study, we showed that persistent TGEV infection induces an EMT in porcine intestinal columnar epithelial cells (IPEC-J2) and enhances the adhesion of the secondary pathogen ETEC K88. Additional experiments suggest that integrin α5 and fibronectin play an important role in TGEV-enhanced ETEC K88 adhesion. Reversal of EMT reduces the expression of integrin α5 and fibronectin and also reduces ETEC K88 adhesion. We conclude that TGEV infection triggers EMT and facilitates dual infection. Our results provide new insights into secondary infection and suggest that targeted anti-EMT therapy may have implications for the prevention and treatment of secondary infection.",,"['Xia, Lu', 'Dai, Lei', 'Yu, Qinghua', 'Yang, Qian']",,,,
,PMC,Uncoupling of Protease trans-Cleavage and Helicase Activities in Pestivirus NS3,http://dx.doi.org/10.1128/JVI.01094-17,PMC5640827,,,"The nonstructural protein NS3 from the Flaviviridae family is a multifunctional protein that contains an N-terminal protease and a C-terminal helicase, playing essential roles in viral polyprotein processing and genome replication. Here we report a full-length crystal structure of the classical swine fever virus (CSFV) NS3 in complex with its NS4A protease cofactor segment (PCS) at a 2.35-Å resolution. The structure reveals a previously unidentified ∼2,200-Å(2) intramolecular protease-helicase interface comprising three clusters of interactions, representing a “closed” global conformation related to the NS3-NS4A cis-cleavage event. Although this conformation is incompatible with protease trans-cleavage, it appears to be functionally important and beneficial to the helicase activity, as the mutations designed to perturb this conformation impaired both the helicase activities in vitro and virus production in vivo. Our work reveals important features of protease-helicase coordination in pestivirus NS3 and provides a key basis for how different conformational states may explicitly contribute to certain functions of this natural protease-helicase fusion protein. IMPORTANCE Many RNA viruses encode helicases to aid their RNA genome replication and transcription by unwinding structured RNA. Being naturally fused to a protease participating in viral polyprotein processing, the NS3 helicases encoded by the Flaviviridae family viruses are unique. Therefore, how these two enzyme modules coordinate in a single polypeptide is of particular interest. Here we report a previously unidentified conformation of pestivirus NS3 in complex with its NS4A protease cofactor segment (PCS). This conformational state is related to the protease cis-cleavage event and is optimal for the function of helicase. This work provides an important basis to understand how different enzymatic activities of NS3 may be achieved by the coordination between the protease and helicase through different conformational states.",,"['Zheng, Fengwei', 'Lu, Guoliang', 'Li, Ling', 'Gong, Peng', 'Pan, Zishu']",,,,
,PMC,Transmissible Viral Vaccines,http://dx.doi.org/10.1016/j.tim.2017.09.007,PMC5777272,,,"Genetic engineering now enables the design of live viral vaccines that are potentially transmissible. Some designs merely modify a single viral genome to improve on the age-old method of attenuation whereas other designs create chimeras of viral genomes. Transmission has the benefit of increasing herd immunity above that achieved by direct vaccination alone but also increases the opportunity for vaccine evolution, which typically undermines vaccine utility. Different designs have different epidemiological consequences but also experience different evolution. Approaches that integrate vaccine engineering with an understanding of evolution and epidemiology will reap the greatest benefit from vaccine transmission.",,"['Bull, James J.', 'Smithson, Mark W.', 'Nuismer, Scott L.']",,,,
,PMC,Extended models for nosocomial infection: parameter estimation and model selection,http://dx.doi.org/10.1093/imammb/dqx010,PMC6145396,,,"We consider extensions to previous models for patient level nosocomial infection in several ways, provide a specification of the likelihoods for these new models, specify new update steps required for stochastic integration, and provide programs that implement these methods to obtain parameter estimates and model choice statistics. Previous susceptible-infected models are extended to allow for a latent period between initial exposure to the pathogen and the patient becoming themselves infectious, and the possibility of decolonization. We allow for multiple facilities, such as acute care hospitals or long-term care facilities and nursing homes, and for multiple units or wards within a facility. Patient transfers between units and facilities are tracked and accounted for in the models so that direct importation of a colonized individual from one facility or unit to another might be inferred. We allow for constant transmission rates, rates that depend on the number of colonized individuals in a unit or facility, or rates that depend on the proportion of colonized individuals. Statistical analysis is done in a Bayesian framework using Markov chain Monte Carlo methods to obtain a sample of parameter values from their joint posterior distribution. Cross validation, deviance information criterion and widely applicable information criterion approaches to model choice fit very naturally into this framework and we have implemented all three. We illustrate our methods by considering model selection issues and parameter estimation for data on methicilin-resistant Staphylococcus aureus surveillance tests over 1 year at a Veterans Administration hospital comprising seven wards.",,"['Thomas, Alun', 'Khader, Karim', 'Redd, Andrew', 'Leecaster, Molly', 'Zhang, Yue', 'Jones, Makoto', 'Greene, Tom', 'Samore, Matthew']",,,,
,PMC,Foldability of a natural de novo evolved protein,http://dx.doi.org/10.1016/j.str.2017.09.006,PMC5677532,,,"The de novo evolution of protein-coding genes from noncoding DNA is emerging as a source of molecular innovation in biology. Studies of random sequence libraries, however, suggest that young de novo proteins will not fold into compact, specific structures typical of native globular proteins. Here we show that Bsc4, a functional, natural de novo protein encoded by a gene that evolved recently from noncoding DNA in the yeast S. cerevisiae, folds to a partially specific three-dimensional structure. Bsc4 forms soluble, compact oligomers with high β-sheet content and a hydrophobic core, and undergoes cooperative, reversible denaturation. Bsc4 lacks a specific quaternary state, however, existing instead as a continuous distribution of oligomer sizes, and binds dyes indicative of amyloid oligomers or molten globules. The combination of native-like and non-native-like properties suggests a rudimentary fold that could potentially act as a functional intermediate in the emergence of new folded proteins de novo.",,"['Bungard, Dixie', 'Copple, Jacob S.', 'Yan, Jing', 'Chhun, Jimmy J.', 'Kumirov, Vlad K.', 'Foy, Scott G.', 'Masel, Joanna', 'Wysocki, Vicki H.', 'Cordes, Matthew H. J.']",,,,
,PMC,Diverse viruses require the calcium transporter SPCA1 for maturation and spread,http://dx.doi.org/10.1016/j.chom.2017.09.002,PMC5952603,,,"Respiratory and arthropod-borne viral infections are a global threat due to the lack of effective antivirals and vaccines. A potential strategy is to target host proteins required for viruses but non-essential for the host. To identify such proteins, we performed a genome-wide knockout screen in human haploid cells and identified the calcium pump SPCA1. SPCA1 is required by viruses from the Paramyxo-, Flavi-, and Togaviridae families, including measles, dengue, West Nile, Zika, and chikungunya viruses. Calcium transport activity is required for SPCA1 to promote virus spread. SPCA1 regulates proteases within the trans-Golgi network that require calcium for their activity and are critical for virus glycoprotein maturation. Consistent with these findings, viral glycoproteins fail to mature in SPCA1-deficient cells preventing viral spread, which is evident even in cells with partial loss of SPCA1. Thus, SPCA1 is an attractive antiviral host target for a broad spectrum of established and emerging viral infections.",,"['Hoffmann, H.-Heinrich', 'Schneider, William M', 'Blomen, Vincent A', 'Scull, Margaret A', 'Hovnanian, Alain', 'Brummelkamp, Thijn R', 'Rice, Charles M']",,,,
,PMC,Impact of Respiratory Viral Panel Polymerase Chain Reaction Assay Turnaround Time on Length of Stay and Antibiotic Use in Patients With Respiratory Viral Illnesses,http://dx.doi.org/10.1177/0018578717731573,PMC5735740,,,"Background: Respiratory viral illnesses account for many hospitalizations and inappropriate antibiotic use. Respiratory viral panels by polymerase chain reaction (RVP-PCR) provide a reliable means of diagnosis. In 2015, the RVP-PCR assay at our institution was switched from respiratory viral panel (RVP) to rapid respiratory panel (rapid RP), which has a faster turnaround time (24 hours vs 12 hours, respectively). The purpose of this study was to evaluate the effect of RVP-PCR tests on duration of antibiotic use and length of stay (LOS) in hospitalized patients. Methods: We performed a retrospective chart review of patients who had a RVP-PCR ordered within a 1-year time period before and after the assay switch. Patients who were pregnant, had received antibiotics within 30 days prior to admission, were not discharged, or had not completed antibiotics by end of study period were excluded. Results: Data were obtained from a total of 140 patients (70 in each group). Of these, 25 (35.7%) in the RVP group and 28 (40.0%) in the rapid RP group had a positive result. The median LOS was 4.5 days (IQR, 3-9 days) in the RVP group and 5 days (IQR, 3-9 days) in the rapid RP group (P = .78). The median duration of antibiotic use was 4 days (IQR, 2-7 days) in the RVP group and 5 days (IQR, 1-7 days) in the rapid RP group (P = .8). Conclusion: Despite faster turnaround time, there was no significant difference in duration of antibiotic use, or LOS between the RVP and rapid RP groups.",,"['Choi, Sebastian', 'Kabir, Rubiya', 'Gautam-Goyal, Pranisha', 'Malhotra, Prashant']",,,,
,PMC,NS1 is the fluid for “flu-transmission”,http://dx.doi.org/10.1073/pnas.1715239114,PMC5651787,,,,,"['Watanabe, Tokiko', 'Imai, Masaki', 'Kawaoka, Yoshihiro']",,,,
,PMC,Transgene expression in the genome of Middle East respiratory syndrome coronavirus based on a novel reverse genetics system utilizing Red-mediated recombination cloning,http://dx.doi.org/10.1099/jgv.0.000919,PMC5725994,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a high-priority pathogen in pandemic preparedness research. Reverse genetics systems are a valuable tool to study viral replication and pathogenesis, design attenuated vaccines and create defined viral assay systems for applications such as antiviral screening. Here we present a novel reverse genetics system for MERS-CoV that involves maintenance of the full-length viral genome as a cDNA copy inserted in a bacterial artificial chromosome amenable to manipulation by homologue recombination, based on the bacteriophage λ Red recombination system. Based on a full-length infectious MERS-CoV cDNA clone, optimal genomic insertion sites and expression strategies for GFP were identified and used to generate a reporter MERS-CoV expressing GFP in addition to the complete set of viral proteins. GFP was genetically fused to the N-terminal part of protein 4a, from which it is released during translation via porcine teschovirus 2A peptide activity. The resulting reporter virus achieved titres nearly identical to the wild-type virus 48 h after infection of Vero cells at m.o.i. 0.001 (1×10(5) p.f.u. ml(−1) and 3×10(5) p.f.u. ml(−1), respectively), and allowed determination of the 50 % inhibitory concentration for the known MERS-CoV inhibitor cyclosporine A based on fluorescence readout. The resulting value was 2.41 µM, which corresponds to values based on wild-type virus. The reverse genetics system described herein can be efficiently mutated by Red-mediated recombination. The GFP-expressing reporter virus contains the full set of MERS-CoV proteins and achieves wild-type titres in cell culture.",,"['Muth, Doreen', 'Meyer, Benjamin', 'Niemeyer, Daniela', 'Schroeder, Simon', 'Osterrieder, Nikolaus', 'Müller, Marcel Alexander', 'Drosten, Christian']",,,,
,PMC,"A Smart Card-Based Electronic School Absenteeism System for Influenza-Like Illness Surveillance in Hong Kong: Design, Implementation, and Feasibility Assessment",http://dx.doi.org/10.2196/publichealth.6810,PMC5650675,28986338,CC BY,"BACKGROUND: School-aged children have the highest incidence of respiratory virus infections each year, and transmission of respiratory viruses such as influenza virus can be a major concern in school settings. School absenteeism data have been employed as a component of influenza surveillance systems in some locations. Data timeliness and system acceptance remain as key determinants affecting the usefulness of a prospective surveillance system. OBJECTIVE: The aim of this study was to assess the feasibility of implementing an electronic school absenteeism surveillance system using smart card–based technology for influenza-like illness (ILI) surveillance among a representative network of local primary and secondary schools in Hong Kong. METHODS: We designed and implemented a surveillance system according to the Protocol for a Standardized information infrastructure for Pandemic and Emerging infectious disease Response (PROSPER). We employed an existing smart card–based education and school administration platform for data capture, customized the user interface, and used additional back end systems built for other downstream surveillance steps. We invited local schools to participate and collected absenteeism data by the implemented system. We compared temporal trend of the absenteeism data with data from existing community sentinel and laboratory surveillance data. RESULTS: We designed and implemented an ILI surveillance system utilizing smart card–based attendance tracking approach for data capture. We implemented the surveillance system in a total of 107 schools (including 66 primary schools and 41 secondary schools), covering a total of 75,052 children. The system successfully captured information on absences for 2 consecutive academic years (2012-2013 and 2013-2014). The absenteeism data we collected from the system reflected ILI activity in the community, with an upsurge in disease activity detected up to 1 to 2 weeks preceding other existing surveillance systems. CONCLUSIONS: We designed and implemented a novel smart card technology–based school absenteeism surveillance system. Our study demonstrated the feasibility of building a large-scale surveillance system riding on a routinely adopted data collection approach and the use of simple system enhancement to minimize workload implication and enhance system acceptability. Data from this system have potential value in supplementing existing sentinel influenza surveillance for situational awareness of influenza activity in the community.",2017 Oct 6,"['Ip, Dennis KM', 'Lau, Eric HY', 'So, Hau Chi', 'Xiao, Jingyi', 'Lam, Chi Kin', 'Fang, Vicky J', 'Tam, Yat Hung', 'Leung, Gabriel M', 'Cowling, Benjamin J']",JMIR Public Health Surveill,,,
,PMC,Emerging infectious diseases: prediction and detection,http://dx.doi.org/10.14745/ccdr.v43i10a03,PMC5764723,,,"Emerging infectious diseases (EIDs), including West Nile virus, severe acute respiratory syndrome (SARS) and Lyme disease, have had a direct effect within Canada, while many more EIDs such as Zika, chikungunya and Ebola are a threat to Canadians while travelling. Over 75% of EIDs affecting humans are, or were originally, zoonoses (infectious diseases transmitted from animals to humans). There are two main ways by which infectious diseases can emerge: by changes in their geographical ranges and by adaptive emergence, a genetic change in a microorganism that results in it becoming capable of invading a new niche, often by jumping to a new host species such as humans. Diseases can appear to emerge simply because we become capable of detecting and diagnosing them. Management of EID events is a key role of public health globally and a considerable challenge for clinical care. Increasingly, emphasis is being placed on predicting EID occurrence to “get ahead of the curve” – that is, allowing health systems to be poised to respond to them, and public health to be ready to prevent them. Predictive models estimate where and when EIDs may occur and the levels of risk they pose. Evaluation of the internal and external drivers that trigger emergence events is increasingly considered in predicting EID events. Currently, global changes are driving increasing occurrence of EIDs, but our capacity to prevent and deal with them is also increasing. Web-based scanning and analysis methods are increasingly allowing us to detect EID outbreaks, modern genomics and bioinformatics are increasing our ability to identify their genetic and geographical origins, while developments in geomatics and earth observation will enable more real-time tracking of outbreaks. EIDs will, however, remain a key, global public health challenge in a globalized world where demographic, climatic, and other environmental changes are altering the interactions between hosts and pathogen in ways that increase spillover from animals to humans and global spread.",,"['Ogden, NH', 'AbdelMalik, P', 'Pulliam, JRC']",,,,
,PMC,Chicken galectin-1B inhibits Newcastle disease virus adsorption and replication through binding to hemagglutinin–neuraminidase (HN) glycoprotein,http://dx.doi.org/10.1074/jbc.M116.772897,PMC5724002,,,"Galectin-1 is an important immunoregulatory factor and can mediate the host–pathogen interaction via binding glycans on the surface of various viruses. We previously reported that avian respiratory viruses, including lentogenic Newcastle disease virus (NDV), can induce up-regulation of chicken galectin (CG)-1B in the primary target organ. In this study, we investigated whether CG-1B participated in the infectious process of NDV in chickens. We demonstrated that velogenic NDV induced up-regulation of CG-1B in target organs. We also found that CG-1B directly bound to NDV virions and inhibited their hemagglutination activity in vitro. We confirmed that CG-1B interacted with NDV hemagglutinin–neuraminidase (HN) glycoprotein, in which the specific G4 N-glycans significantly contributed to the interaction between CG-1B and HN glycoprotein. The presence of extracellular CG-1B, rather than the internalization process, inhibited adsorption of NDV. The interaction between intracellular CG-1B and NDV HN glycoproteins inhibited cell-surface expression of HN glycoprotein and reduced the titer of progeny virus in NDV-infected DF-1 cells. Significantly, the replication of parental and HN glycosylation mutant viruses in CG-1B knockdown and overexpression cells demonstrated that the replication of NDV was correlated with the expression of CG-1B in a specific glycan-dependent manner. Collectively, our results indicate that CG-1B has anti-NDV activity by binding to N-glycans on HN glycoprotein.",,"['Sun, Junfeng', 'Han, Zongxi', 'Qi, Tianming', 'Zhao, Ran', 'Liu, Shengwang']",,,,
,PMC,,,PMC6824915,,,,,,,,,
,PMC,Expanded subgenomic mRNA transcriptome and coding capacity of a nidovirus,http://dx.doi.org/10.1073/pnas.1706696114,PMC5651751,,,"Members of the order Nidovirales express their structural protein ORFs from a nested set of 3′ subgenomic mRNAs (sg mRNAs), and for most of these ORFs, a single genomic transcription regulatory sequence (TRS) was identified. Nine TRSs were previously reported for the arterivirus Simian hemorrhagic fever virus (SHFV). In the present study, which was facilitated by next-generation sequencing, 96 SHFV body TRSs were identified that were functional in both infected MA104 cells and macaque macrophages. The abundance of sg mRNAs produced from individual TRSs was consistent over time in the two different cell types. Most of the TRSs are located in the genomic 3′ region, but some are in the 5′ ORF1a/1b region and provide alternative sources of nonstructural proteins. Multiple functional TRSs were identified for the majority of the SHFV 3′ ORFs, and four previously identified TRSs were found not to be the predominant ones used. A third of the TRSs generated sg mRNAs with variant leader–body junction sequences. Sg mRNAs encoding E′, GP2, or ORF5a as their 5′ ORF as well as sg mRNAs encoding six previously unreported alternative frame ORFs or 14 previously unreported C-terminal ORFs of known proteins were also identified. Mutation of the start codon of two C-terminal ORFs in an infectious clone reduced virus yield. Mass spectrometry detected one previously unreported protein and suggested translation of some of the C-terminal ORFs. The results reveal the complexity of the transcriptional regulatory mechanism and expanded coding capacity for SHFV, which may also be characteristic of other nidoviruses.",,"['Di, Han', 'Madden, Joseph C.', 'Morantz, Esther K.', 'Tang, Hsin-Yao', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Brinton, Margo A.']",,,,
,PMC,IL-35 may maintain homeostasis of the immune microenvironment in periodontitis,http://dx.doi.org/10.3892/etm.2017.5255,PMC5740813,,,"T lymphocyte cells, including regulatory T (Treg) and T helper 17 cells, have important roles in the human periodontium. However, the basis for Treg cytokine expression in various compartments of the periodontium remains unclear. The aim of the present study was to investigate the expression of interleukin (IL)-35 in the peripheral blood mononuclear cells (PBMCs) and periodontal tissues of patients with chronic periodontitis (CP), with a view to understanding its role in this disease, and ultimately providing improved treatments. Peripheral blood, periodontal tissues and gingival crevicular fluids (GCFs) were collected from patients with CP or impacted teeth, the latter serving as healthy controls. The expression levels of IL-35 subunit mRNAs in PBMCs and periodontal tissues were determined using reverse transcription-quantitative polymerase chain reaction, while the IL-35 protein expression in GCFs and sera was quantified by ELISA. The relative expression of IL-35 subunit mRNAs in the affected tissues of patients with CP was significantly higher compared with that in samples from healthy controls (P<0.05). The mean concentration of IL-35 protein in the GCFs and sera of patients with periodontitis was also significantly higher compared with that in samples from healthy controls (P<0.001). IL-35 protein and periodontal clinical indicators were negatively correlated. It was hypothesized that the increased level of IL-35 plays a protective role in periodontal disease by maintaining immune system homeostasis and dampening the inflammatory response, and highlights IL-35 as a potential new therapy for the treatment of periodontitis.",,"['Jin, Ying', 'Liu, Dixin', 'Lin, Xiaoping']",,,,
,PMC,Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion,http://dx.doi.org/10.1073/pnas.1708727114,PMC5651768,,,"The tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks of deadly pneumonia. The coronavirus spike (S) glycoprotein initiates infection by promoting fusion of the viral and cellular membranes through conformational changes that remain largely uncharacterized. Here we report the cryoEM structure of a coronavirus S glycoprotein in the postfusion state, showing large-scale secondary, tertiary, and quaternary rearrangements compared with the prefusion trimer and rationalizing the free-energy landscape of this conformational machine. We also biochemically characterized the molecular events associated with refolding of the metastable prefusion S glycoprotein to the postfusion conformation using limited proteolysis, mass spectrometry, and single-particle EM. The observed similarity between postfusion coronavirus S and paramyxovirus F structures demonstrates that a conserved refolding trajectory mediates entry of these viruses and supports the evolutionary relatedness of their fusion subunits. Finally, our data provide a structural framework for understanding the mode of neutralization of antibodies targeting the fusion machinery and for engineering next-generation subunit vaccines or inhibitors against this medically important virus family.",,"['Walls, Alexandra C.', 'Tortorici, M. Alejandra', 'Snijder, Joost', 'Xiong, Xiaoli', 'Bosch, Berend-Jan', 'Rey, Felix A.', 'Veesler, David']",,,,
,PMC,Inhibition of USP10 induces degradation of oncogenic FLT3,http://dx.doi.org/10.1038/nchembio.2486,PMC6314479,,,"Oncogenic FLT3 kinase is an important therapeutic target in acute myeloid leukemia (AML), however clinical responses to small molecule kinase inhibitors are short-lived due to rapid emergence of resistance as a consequence of point mutations or compensatory increases in FLT3 expression. We sought to develop a complementary pharmacological approach whereby proteasome-mediated FLT3 degradation could be promoted by identifying inhibitors of the deubiquitinating enzyme(s) (DUBs) responsible for cleaving ubiquitin from FLT3. As the relevant DUBs for FLT3 are not known, we assembled a focused library of most reported small molecule DUB inhibitors and performed a cellular phenotypic screen to identify compounds that could induce degradation of oncogenic FLT3. Subsequent target deconvolution efforts allowed us to identify USP10 as the critical DUB required to stabilize FLT3. Targeting USP10 showed efficacy in FLT3-ITD positive pre-clinical models of AML, including cell lines, primary patient specimens and mouse models of oncogenic FLT3-driven leukemia.",,"['Weisberg, Ellen L.', 'Schauer, Nathan J.', 'Yang, Jing', 'Lamberto, Ilaria', 'Doherty, Laura', 'Bhatt, Shruti', 'Nonami, Atsushi', 'Meng, Chengcheng', 'Letai, Anthony', 'Wright, Renee', 'Tiv, Hong', 'Gokhale, Prafulla C.', 'Ritorto, Maria Stella', 'De Cesare, Virginia', 'Trost, Matthias', 'Christodoulou, Alexandra', 'Christie, Amanda', 'Weinstock, David M.', 'Adamia, Sophia', 'Stone, Richard', 'Chauhan, Dharminder', 'Anderson, Kenneth C.', 'Seo, Hyuk-Soo', 'Dhe-Paganon, Sirano', 'Sattler, Martin', 'Gray, Nathanael S.', 'Griffin, James D.', 'Buhrlage, Sara J.']",,,,
,PMC,Feline meningoencephalomyelitis of unknown origin: A retrospective analysis of 16 cases,,PMC5603942,,,"This study aimed to describe the signalment, clinical signs, magnetic resonance imaging (MRI) findings, cerebrospinal fluid (CSF) analysis, treatment, and outcome of feline meningoencephalomyelitis of unknown origin (FMUO). Medical records from 16 cats meeting the inclusion criteria of CSF pleocytosis, negative CSF polymerase chain reaction (PCR)-infectious disease results, and characteristic MRI findings were retrospectively reviewed. Median age was 9.4 years. Clinical signs included ataxia, proprioceptive deficits, seizures, and spinal hyperesthesia. The CSF nucleated cell count was increased (median 70.7 cells/μL), with predominantly mixed pleocytosis and CSF protein concentration was increased in 15/16 cats. Magnetic resonance imaging showed intraparenchymal infiltrative ill-defined lesions in 13 cases. All cats received a corticosteroid-based treatment protocol; additional therapies included lomustine, cytarabine, and anticonvulsant medications. Mild neurological signs were recorded in 5/12 cats but 7/12 cats were neurologically normal at re-examination. This represents the first study of feline MUO, highlighting FMUO as an important differential diagnosis in cats with variable neurological presentation. Prognosis appears to be good with immunomodulatory therapy.",,"['Negrin, Arianna', 'Spencer, Sarah', 'Cherubini, Giunio Bruto']",,,,
,PMC,Web-Based Surveillance of Illness in Childcare Centers,http://dx.doi.org/10.1089/hs.2016.0124,PMC6913116,,,"School absenteeism is an inefficient and unspecific metric for measuring community illness and does not provide surveillance during summertime. Web-based biosurveillance of childcare centers may represent a novel way to efficiently monitor illness outbreaks year-round. A web-based biosurveillance program (sickchildcare.org) was created and implemented in 4 childcare centers in a single Michigan county. Childcare providers were trained to report sick children who required exclusion or had parent-reported absences due to illness. Deidentified data on age range, number of illnesses, and illness categories were collected. Weekly electronic reports were sent to the county public health department. Data for reports were gathered beginning in December 2013 and were summarized using descriptive statistics. A total of 385 individual episodes of illness occurred during the study period. Children with reported illness were infants (16%, n = 61), toddlers (38%, n = 148), and preschoolers (46%, n = 176). Illness categories included: fever (30%, n = 116), gastroenteritis (30%, n = 115), influenzalike illness (8%, n = 32), cold without fever (13%, n = 51), rash (7%, n = 26), conjunctivitis (1%, n = 3), ear infection (1%, n = 5), and other (10%, n = 37). The majority of reports were center exclusions (55%, n = 214); others were absences (45%, n = 171). The detection of a gastroenteritis outbreak by web-based surveillance during winter 2013-14 preceded county health reports by 3 weeks; an additional outbreak of hand-foot-mouth disease was detected during June 2014 when standard school-based surveillance was not available. Web-based biosurveillance of illness in childcare centers represents a novel and feasible method to detect disease trends earlier and year-round compared to standard school-based disease surveillance.",,"['Schellpfeffer, Natalie', 'Collins, Abaigeal', 'Brousseau, David C.', 'Martin, Emily T.', 'Hashikawa, Andrew']",,,,
,PMC,"Serosurvey of Malsoor virus among Rousettus leschenaulti bat & human population residing nearby Robber's cave, Mahabaleshwar, Maharashtra, India",http://dx.doi.org/10.4103/ijmr.IJMR_301_16,PMC5819039,29434071,CC BY-NC-SA,,2017 Oct,"['Yadav, Pragya', 'Deoshatwar, Avinash', 'Shete, Anita', 'Tandale, Babasaheb', 'Patil, Deepak', 'Dalal, Shital', 'Mourya, Devendra']",Indian J Med Res,,,
,PMC,"The Forgotten Plague: Psychiatric Manifestations of Ebola, Zika, and Emerging Infectious Diseases",http://dx.doi.org/10.4103/jgid.jgid_66_17,PMC5750439,29302150,CC BY-NC-SA,"The media and public health generally focus on the biological and physical ramifications of epidemics. Mental health issues that coincide with emerging diseases and epidemics are rarely examined and sometimes, even eschewed due to cultural considerations. Psychiatric manifestations of various infectious diseases, especially with a focus on Ebola Virus disease (EVD) and Zika Virus, are discussed in this commentary to illustrate the continued need of care after the resolution of the actual illness. Various infectious diseases have associations with mental illness, such as an increased risk of obsessive-compulsive disorders and Tourette syndrome in children with Group B streptococcal infection. Current EVD literature does not demonstrate a strong association of mental illness symptoms or diseases but there is a necessity of care that extends beyond the illness. Patients and their families experience depression, anxiety, trauma, suicidal ideation, panic and other manifestations. Zika virus has been associated neuronal injury, genetic alteration that affects fetal development and detrimental maternal mental health symptoms are being documented. While funding calls from the international community are present, there are no specific epidemiological data or fiscal estimates solely for mental health during or after infectious diseases epidemics or disasters that support health care providers and strengthen policies and procedures for responding to such situations. Therefore, those on the frontlines of epidemics including emergency physicians, primary care providers and infectious disease specialists should serve communicate this need and advocate for sustained and increased funding for mental health programs to heighten public awareness regarding acute psychiatric events during infectious diseases outbreaks and offer treatment and support when necessary.",2017 Oct-Dec,"['Tucci, Veronica', 'Moukaddam, Nidal', 'Meadows, Jonathan', 'Shah, Suhal', 'Galwankar, Sagar C', 'Kapur, G Bobby']",J Glob Infect Dis,,,
,PMC,A potent germline-like human monoclonal antibody targets a pH-sensitive epitope on H7N9 influenza hemagglutinin,http://dx.doi.org/10.1016/j.chom.2017.08.011,PMC6290738,,,"The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a human monoclonal antibody, m826, that binds to H7 hemagglutinin (HA) and protects against H7N9 infection. m826 binds to H7N9 HA with subnanomolar affinity at acidic pH and 10-fold lower affinity at neutral pH. The high-resolution (1.9 Å) crystal structure of m826 complexed with H7N9 HA indicates that m826 binds an epitope that may be fully exposed upon pH-induced conformational changes in HA. m826 fully protects mice against lethal challenge with H7N9 virus through mechanisms likely involving antibody-dependent cell-mediated cytotoxicity (ADCC). Interestingly, immunogenetic analysis indicates that m826 is a germline antibody and m826-like sequences can be identified in H7N9-infected patients, healthy adults and newborn babies. These m826 properties offer a template for H7N9 vaccine immunogens, a promising candidate therapeutic, and a tool for exploring mechanisms of virus infection inhibition by antibodies.",,"['Yu, Fei', 'Song, He', 'Wu, Yanling', 'Young Chang, So', 'Wang, Lili', 'Li, Wei', 'Hong, Binbin', 'Xia, Shuai', 'Wang, Chunyu', 'Khurana, Surender', 'Feng, Yang', 'Wang, Yanping', 'Sun, Zhiwu', 'He, Biao', 'Hou, Dongni', 'Manischewitz, Jody', 'King, Lisa R.', 'Song, Yuanlin', 'Min, Ji-Young', 'Golding, Hana', 'Ji, Xinhua', 'Lu, Lu', 'Jiang, Shibo', 'Dimitrov, Dimiter S.', 'Ying, Tianlei']",,,,
,PMC,Hepatitis C Virus Induces the Localization of Lipid Rafts to Autophagosomes for Its RNA Replication,http://dx.doi.org/10.1128/JVI.00541-17,PMC5625520,,,"Autophagy plays important roles in maintaining cellular homeostasis. It uses double- or multiple-membrane vesicles termed autophagosomes to remove protein aggregates and damaged organelles from the cytoplasm for recycling. Hepatitis C virus (HCV) has been shown to induce autophagy to enhance its own replication. Here we describe a procedure that combines membrane flotation and affinity chromatography for the purification of autophagosomes from cells that harbor an HCV subgenomic RNA replicon. The purified autophagosomes had double- or multiple-membrane structures with a diameter ranging from 200 nm to 600 nm. The analysis of proteins associated with HCV-induced autophagosomes by proteomics led to the identification of HCV nonstructural proteins as well as proteins involved in membrane trafficking. Notably, caveolin-1, caveolin-2, and annexin A2, which are proteins associated with lipid rafts, were also identified. The association of lipid rafts with HCV-induced autophagosomes was confirmed by Western blotting, immunofluorescence microscopy, and immunoelectron microscopy. Their association with autophagosomes was also confirmed in HCV-infected cells. The association of lipid rafts with autophagosomes was specific to HCV, as it was not detected in autophagosomes induced by nutrient starvation. Further analysis indicated that the autophagosomes purified from HCV replicon cells could mediate HCV RNA replication in a lipid raft-dependent manner, as the depletion of cholesterol, a major component of lipid rafts, from autophagosomes abolished HCV RNA replication. Our studies thus demonstrated that HCV could specifically induce the association of lipid rafts with autophagosomes for its RNA replication. IMPORTANCE HCV can cause severe liver diseases, including cirrhosis and hepatocellular carcinoma, and is one of the most important human pathogens. Infection with HCV can lead to the reorganization of membrane structures in its host cells, including the induction of autophagosomes. In this study, we developed a procedure to purify HCV-induced autophagosomes and demonstrated that HCV could induce the localization of lipid rafts to autophagosomes to mediate its RNA replication. This finding provided important information for further understanding the life cycle of HCV and its interaction with the host cells.",,"['Kim, Ja Yeon', 'Wang, Linya', 'Lee, Jiyoung', 'Ou, Jing-hsiung James']",,,,
,PMC,Zinc Finger-Containing Cellular Transcription Corepressor ZBTB25 Promotes Influenza Virus RNA Transcription and Is a Target for Zinc Ejector Drugs,http://dx.doi.org/10.1128/JVI.00842-17,PMC5625503,,,"Influenza A virus (IAV) replication relies on an intricate interaction between virus and host cells. How the cellular proteins are usurped for IAV replication remains largely obscure. The aim of this study was to search for novel and potential cellular factors that participate in IAV replication. ZBTB25, a transcription repressor of a variety of cellular genes, was identified by an RNA interference (RNAi) genomic library screen. Depletion of ZBTB25 significantly reduced IAV production. Conversely, overexpression of ZBTB25 enhanced it. ZBTB25 interacted with the viral RNA-dependent RNA polymerase (RdRp) protein and modulated its transcription activity. In addition, ZBTB25 also functioned as a viral RNA (vRNA)-binding protein, binding preferentially to the U-rich sequence within the 5′ untranslated region (UTR) of vRNA. Both protein-protein and protein-RNA interactions involving ZBTB25 facilitated viral RNA transcription and replication. In addition, ZBTB25 suppressed interferon production, further enhancing viral replication. ZBTB25-associated functions required an intact zinc finger domain and posttranslational SUMO-1 modification of ZBTB25. Furthermore, treatment with disulfiram (a zinc ejector) of ZBTB25-overexpressing cells showed significantly reduced IAV production as a result of reduced RNA synthesis. Our findings indicate that IAV usurps ZBTB25 for IAV RNA synthesis and serves as a novel and potential therapeutic antiviral target. IMPORTANCE IAV-induced seasonal influenza causes severe illness and death in high-risk populations. However, IAV has developed resistance to current antiviral drugs due to its high mutation rate. Therefore, development of drugs targeting cellular factors required for IAV replication is an attractive alternative for IAV therapy. Here, we discovered a cellular protein, ZBTB25, that enhances viral RdRp activity by binding to both viral RdRp and viral RNA to stimulate viral RNA synthesis. A unique feature of ZBTB25 in the regulation of viral replication is its dual transcription functions, namely, promoting viral RNA transcription through binding to the U-rich region of vRNA and suppressing cellular interferon production. ZBTB25 contains a zinc finger domain that is required for RNA-inhibitory activity by chelating zinc ions. Disulfiram treatment disrupts the zinc finger functions, effectively repressing IAV replication. Based on our findings, we demonstrate that ZBTB25 regulates IAV RNA transcription and replication and serves as a promising antiviral target for IAV treatment.",,"['Chen, Shu-Chuan', 'Jeng, King-Song', 'Lai, Michael M. C.']",,,,
,PMC,Highly Pathogenic New World Arenavirus Infection Activates the Pattern Recognition Receptor Protein Kinase R without Attenuating Virus Replication in Human Cells,http://dx.doi.org/10.1128/JVI.01090-17,PMC5625494,,,"The arenavirus family consists of several highly pathogenic viruses, including the Old World (OW) arenavirus Lassa fever virus (LASV) and the New World (NW) Junin virus (JUNV) and Machupo virus (MACV). Host response to infection by these pathogenic arenaviruses is distinct in many aspects. JUNV and MACV infections readily induce an interferon (IFN) response in human cells, while LASV infection usually triggers an undetectable or weak IFN response. JUNV induces an IFN response through RIG-I, suggesting that the host non-self RNA sensor readily detects JUNV viral RNAs (vRNAs) during infection and activates IFN response. Double-stranded-RNA (dsRNA)-activated protein kinase R (PKR) is another host non-self RNA sensor classically known for its vRNA recognition activity. Here we report that infection with NW arenaviruses JUNV and MACV, but not OW LASV, activated PKR, concomitant with elevated phosphorylation of the translation initiation factor α subunit of eukaryotic initiation factor 2 (eIF2α). Host protein synthesis was substantially suppressed in MACV- and JUNV-infected cells but was only marginally reduced in LASV-infected cells. Despite the antiviral activity known for PKR against many other viruses, the replication of JUNV and MACV was not impaired but was slightly augmented in wild-type (wt) cells compared to that in PKR-deficient cells, suggesting that PKR or PKR activation did not negatively affect JUNV and MACV infection. Additionally, we found an enhanced IFN response in JUNV- or MACV-infected PKR-deficient cells, which was inversely correlated with virus replication. IMPORTANCE The detection of viral RNA by host non-self RNA sensors, including RIG-I and MDA5, is critical to the initiation of the innate immune response to RNA virus infection. Among pathogenic arenaviruses, the OW LASV usually does not elicit an interferon response. However, the NW arenaviruses JUNV and MACV readily trigger an IFN response in a RIG-I-dependent manner. Here, we demonstrate for the first time that pathogenic NW arenaviruses JUNV and MACV, but not the OW arenavirus LASV, activated the dsRNA-dependent PKR, another host non-self RNA sensor, during infection. Interestingly, the replication of JUNV and MACV was not restricted but was rather slightly augmented in the presence of PKR. Our data provide new evidence for a distinct interplay between host non-self RNA sensors and pathogenic arenaviruses, which also provides insights into the pathogenesis of arenaviruses and may facilitate the design of vaccines and treatments against arenavirus-caused diseases.",,"['Huang, Cheng', 'Kolokoltsova, Olga A.', 'Mateer, Elizabeth J.', 'Koma, Takaaki', 'Paessler, Slobodan']",,,,
,PMC,Potent In Vivo NK Cell-Mediated Elimination of HIV-1-Infected Cells Mobilized by a gp120-Bispecific and Hexavalent Broadly Neutralizing Fusion Protein,http://dx.doi.org/10.1128/JVI.00937-17,PMC5625480,,,"Antibodies bound to human immunodeficiency virus type 1 (HIV-1) envelope protein expressed by infected cells mobilize antibody-dependent cellular cytotoxicity (ADCC) to eliminate the HIV-1-infected cells and thereby suppress HIV-1 infection and delay disease progression. Studies treating HIV-1-infected individuals with latency reactivation agents to reduce their latent HIV-1 reservoirs indicated that their HIV-1-specific immune responses were insufficient to effectively eliminate the reactivated latent HIV-1-infected T cells. Mobilization of ADCC may facilitate elimination of reactivated latent HIV-1-infected cells to deplete the HIV-1 reservoir and contribute to a functional HIV-1 cure. The most effective antibodies for controlling and eradicating HIV-1 infection would likely have the dual capacities of potently neutralizing a broad range of HIV-1 isolates and effectively mobilizing HIV-1-specific ADCC to eliminate HIV-1-infected cells. For this purpose, we constructed LSEVh-LS-F, a broadly neutralizing, defucosylated hexavalent fusion protein specific for both the CD4 and coreceptor gp120-binding sites. LSEVh-LS-F potently inhibited in vivo HIV-1 and simian-human immunodeficiency virus (SHIV) infection in humanized mouse and macaque models, respectively, including in vivo neutralization of HIV-1 strains resistant to the broadly neutralizing antibodies VRC01 and 3BNC117. We developed a novel humanized mouse model to evaluate in vivo human NK cell-mediated elimination of HIV-1-infected cells by ADCC and utilized it to demonstrate that LSEVh-LS-F rapidly mobilized NK cells to eliminate >80% of HIV-1-infected cells in vivo 1 day after its administration. The capacity of LSEVh-LS-F to eliminate HIV-1-infected cells via ADCC combined with its broad neutralization activity supports its potential use as an immunotherapeutic agent to eliminate reactivated latent cells and deplete the HIV-1 reservoir. IMPORTANCE Mobilization of antibody-dependent cellular cytotoxicity (ADCC) to eliminate reactivated latent HIV-1-infected cells is a strategy which may contribute to depleting the HIV-1 reservoir and achieving a functional HIV-1 cure. To more effectively mobilize ADCC, we designed and constructed LSEVh-LS-F, a broadly neutralizing, defucosylated hexavalent fusion protein specific for both the CD4 and coreceptor gp120-binding sites. LSEVh-LS-F potently inhibited in vivo HIV-1 and SHIV infection in humanized mouse and macaque models, respectively, including in vivo neutralization of an HIV-1 strain resistant to the broadly neutralizing antibodies VRC01 and 3BNC117. Using a novel humanized mouse model, we demonstrated that LSEVh-LS-F rapidly mobilized NK cells to eliminate >80% of HIV-1-infected cells in vivo 1 day after its administration. The capacity of LSEVh-LS-F to eliminate HIV-1-infected cells via ADCC combined with its broad neutralization activity supports its potential use as an immunotherapeutic agent to eliminate reactivated latent cells and deplete the HIV-1 reservoir.",,"['Bardhi, Ariola', 'Wu, Yanling', 'Chen, Weizao', 'Li, Wei', 'Zhu, Zhongyu', 'Zheng, Jian Hua', 'Wong, Hing', 'Jeng, Emily', 'Jones, Jennifer', 'Ochsenbauer, Christina', 'Kappes, John C.', 'Dimitrov, Dimiter S.', 'Ying, Tianlei', 'Goldstein, Harris']",,,,
,PMC,Extracellular vesicles as an efficient nanoplatform for the delivery of therapeutics,http://dx.doi.org/10.1080/21645515.2017.1363935,PMC5703411,,,"Extracellular vesicles (EVs) are membrane-derived vesicles that are enriched with RNAs, proteins and other functional molecules. We exploit the unique physical properties of EVs as a promising and advantageous nanoplatform for the delivery of therapeutic drugs and genetic materials. Early successes in the discovery of various disease-related characteristics of EVs have driven a new wave of innovation in developing nanoscale drug-delivery systems (DDSs). Nevertheless, there are several issues that need to be considered during the development of these alternative DDSs, such as standardized isolation and preservation methods, efficient drug encapsulation, mechanisms of drug release and so on. In this mini-review, we summarize the current status and progress of EV-based DDSs as an efficient nanoplatform for therapeutics delivery, followed by a discussion on their challenges and future prospects for clinical translation and applications.",,"['Liu, Chao', 'Gao, Haiyan', 'Lv, Peng', 'Liu, Jingyi', 'Liu, Gang']",,,,
,PMC,Inclusion of MERS-spike protein ELISA in algorithm to determine serologic evidence of MERS-CoV infection,http://dx.doi.org/10.1002/jmv.24948,PMC6158782,,,"The Centers for Disease Control and Prevention (CDC) algorithm for detecting presence of serum antibodies against Middle East Respiratory Syndrome coronavirus (MERS-CoV) in subjects with potential infections with the virus has included screening by indirect ELISA against recombinant nucleocapsid (N) protein and confirmation by immunofluorescent staining of infected monolayers and/or micro-neutralization titration. Other international groups include indirect ELISA assays using the spike (S) protein, as part of their serological determinations. In the current study, we describe development and validation of an indirect MERS-CoV S ELISA to be used as part of our serological determination for evidence of previous exposure to the virus.",,"['Trivedi, Suvang', 'Miao, Congrong', 'Al-Abdallat, Mohammad M.', 'Haddadin, Aktham', 'Alqasrawi, Sultan', 'Iblan, Ibrahim', 'Nsour, Mohannad A.', 'Alsanouri, Tarek', 'Ali, Sami S.', 'Rha, Brian', 'Gerber, Susan I.', 'Payne, Daniel C.', 'Tamin, Azaibi', 'Thornburg, Natalie J.']",,,,
,PMC,Conditions affecting the timing and magnitude of Hendra virus shedding across pteropodid bat populations in Australia,http://dx.doi.org/10.1017/S0950268817002138,PMC5783192,,,"Understanding infection dynamics in animal hosts is fundamental to managing spillover and emergence of zoonotic infections. Hendra virus is endemic in Australian pteropodid bat populations and can be lethal to horses and humans. However, we know little about the factors driving Hendra virus prevalence in resevoir bat populations, making spillover difficult to predict. We use Hendra virus prevalence data collected from 13 000 pooled bat urine samples across space and time to determine if pulses of prevalence are periodic and synchronized across sites. We also test whether site-specific precipitation and temperature affect the amplitude of the largest annual prevalence pulses. We found little evidence for a periodic signal in Hendra virus prevalence. Although the largest amplitude pulses tended to occur over winter, pulses could also occur in other seasons. We found that Hendra virus prevalence was weakly synchronized across sites over short distances, suggesting that prevalence is driven by local-scale effects. Finally, we found that drier conditions in previous seasons and the abundance of Pteropus alecto were positively correlated with the peak annual values of Hendra virus prevalence. Our results suggest that in addition to seasonal effects, bat density and local climatic conditions interact to drive Hendra virus infection dynamics.",,"['PÁEZ, D. J.', 'GILES, J.', 'MCCALLUM, H.', 'FIELD, H.', 'JORDAN, D.', 'PEEL, A. J.', 'PLOWRIGHT, R. K.']",,,,
,PMC,De novo design of covalently constrained mesosize protein scaffolds with unique tertiary structures,http://dx.doi.org/10.1073/pnas.1710695114,PMC5642715,,,"The folding of natural proteins typically relies on hydrophobic packing, metal binding, or disulfide bond formation in the protein core. Alternatively, a 3D structure can be defined by incorporating a multivalent cross-linking agent, and this approach has been successfully developed for the selection of bicyclic peptides from large random-sequence libraries. By contrast, there is no general method for the de novo computational design of multicross-linked proteins with predictable and well-defined folds, including ones not found in nature. Here we use Rosetta and Tertiary Motifs (TERMs) to design small proteins that fold around multivalent cross-linkers. The hydrophobic cross-linkers stabilize the fold by macrocyclic restraints, and they also form an integral part of a small apolar core. The designed CovCore proteins were prepared by chemical synthesis, and their structures were determined by solution NMR or X-ray crystallography. These mesosized proteins, lying between conventional proteins and small peptides, are easily accessible either through biosynthetic precursors or chemical synthesis. The unique tertiary structures and ease of synthesis of CovCore proteins indicate that they should provide versatile templates for developing inhibitors of protein–protein interactions.",,"['Dang, Bobo', 'Wu, Haifan', 'Mulligan, Vikram Khipple', 'Mravic, Marco', 'Wu, Yibing', 'Lemmin, Thomas', 'Ford, Alexander', 'Silva, Daniel-Adriano', 'Baker, David', 'DeGrado, William F.']",,,,
,PMC,Activation of Stimulator of Interferon Genes in Hepatocytes Suppresses the Replication of Hepatitis B Virus,http://dx.doi.org/10.1128/AAC.00771-17,PMC5610522,,,"Induction of interferon and proinflammatory cytokines is a hallmark of the infection of many different viruses. However, hepatitis B virus (HBV) does not elicit a detectable cytokine response in infected hepatocytes. In order to investigate the molecular mechanism underlying the innate immune evasion, a functional cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway was reconstituted in a human hepatoma cell line supporting tetracycline-inducible HBV replication. It was demonstrated that induction of HBV replication neither activated nor inhibited this cytosolic DNA sensing pathway. However, human hepatoma cells, as well as immortalized mouse hepatocytes, express low levels of STING, which upon activation by cGAMP, the natural ligand of STING, led to induction of a proinflammatory cytokine response. Treatment of immortalized mouse hepatocytes supporting HBV replication with either cGAMP or a small molecule pharmacologic STING agonist significantly reduced viral DNA in a STING- and Janus kinase 1-dependent manner. Moreover, cGAMP treatment was able to induce inflammatory cytokine gene expression and inhibit the transcription of covalently closed circular DNA in HBV-infected human hepatoma cells expressing sodium taurocholate cotransporting polypeptide, an essential receptor for HBV infection of hepatocytes. The studies reported here and previously (F. Guo et al., Antimicrob Agents Chemother 59:1273–1281, 2015, https://doi.org/10.1128/AAC.04321-14) thus support the notion that pharmacological activation of STING in macrophages and hepatocytes induces host innate responses that can efficiently control HBV replication. Hence, despite not playing a significant role in host innate immune response to HBV infection of hepatocytes, STING is potentially a valuable target for immunotherapy of chronic hepatitis B.",,"['Guo, Fang', 'Tang, Liudi', 'Shu, Sainan', 'Sehgal, Mohit', 'Sheraz, Muhammad', 'Liu, Bowei', 'Zhao, Qiong', 'Cheng, Junjun', 'Zhao, Xuesen', 'Zhou, Tianlun', 'Chang, Jinhong', 'Guo, Ju-Tao']",,,,
,PMC,"Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection",http://dx.doi.org/10.1080/21645515.2017.1368598,PMC5718803,,,"Tuberculosis (TB) remains a main public health concern and 10.4 million new cases occurred in 2015 around the world. BCG is the only approved vaccine against TB, but has variable efficacy and new vaccines are needed. We developed two new mTB vaccine candidates based on the recombinant fusion proteins, rCMX and rECMX formulated with Advax4, a new combination adjuvant combining delta inulin, CpG oligonucleotide and murabutide. BALB/c mice were immunized three times intramuscularly with these vaccine formulations. Injection of Advax4 alone increased the percentage of lymphatic endothelial cells and activated macrophages (F480/CD11b(+)) in the draining lymph nodes consistent with a chemotactic adjuvant effect. Advax4+CMX and Advax4+ECMX induced the highest levels of IgG1 and IgG2a antibodies against rCMX and rECMX, respectively. Immunized mice challenged with Mycobacterium tuberculosis (Mtb) had increased vaccine-specific Th1 responses in the lungs together with reduced Mtb – associated alveolar damage, although only the Advax4+ECMX vaccine demonstrated significant reduction of lung bacterial load. This study confirmed Advax4+ECMX as a potential TB vaccine candidate, with potential for further optimization and clinical development.",,"['de Paula Oliveira Santos, Bruno', 'Trentini, Monalisa Martins', 'Machado, Renato Beilner', 'Rúbia Nunes Celes, Mara', 'Kipnis, André', 'Petrovsky, Nikolai', 'Junqueira-Kipnis, Ana Paula']",,,,
,PMC,Attenuation of pulmonary ACE2 activity impairs inactivation of des-Arg(9) bradykinin/BKB1R axis and facilitates LPS-induced neutrophil infiltration,http://dx.doi.org/10.1152/ajplung.00498.2016,PMC5866432,,,"Angiotensin-converting enzyme 2 (ACE2) is a terminal carboxypeptidase with important functions in the renin-angiotensin system and plays a critical role in inflammatory lung diseases. ACE2 cleaves single-terminal residues from several bioactive peptides such as angiotensin II. However, few of its substrates in the respiratory tract have been identified, and the mechanism underlying the role of ACE2 in inflammatory lung disease has not been fully characterized. In an effort to identify biological targets of ACE2 in the lung, we tested its effects on des-Arg(9) bradykinin (DABK) in airway epithelial cells on the basis of the hypothesis that DABK is a biological substrate of ACE2 in the lung and ACE2 plays an important role in the pathogenesis of acute lung inflammation partly through modulating DABK/bradykinin receptor B1 (BKB1R) axis signaling. We found that loss of ACE2 function in mouse lung in the setting of endotoxin inhalation led to activation of the DABK/BKB1R axis, release of proinflammatory chemokines such as C-X-C motif chemokine 5 (CXCL5), macrophage inflammatory protein-2 (MIP2), C-X-C motif chemokine 1 (KC), and TNF-α from airway epithelia, increased neutrophil infiltration, and exaggerated lung inflammation and injury. These results indicate that a reduction in pulmonary ACE2 activity contributes to the pathogenesis of lung inflammation, in part because of an impaired ability to inhibit DABK/BKB1R axis-mediated signaling, resulting in more prompt onset of neutrophil infiltration and more severe inflammation in the lung. Our study identifies a biological substrate of ACE2 within the airways, as well as a potential new therapeutic target for inflammatory diseases.",,"['Sodhi, Chhinder P.', 'Wohlford-Lenane, Christine', 'Yamaguchi, Yukihiro', 'Prindle, Thomas', 'Fulton, William B.', 'Wang, Sanxia', 'McCray, Paul B.', 'Chappell, Mark', 'Hackam, David J.', 'Jia, Hongpeng']",,,,
,PMC,A novel immunization approach for dengue infection based on conserved T cell epitopes formulated in calcium phosphate nanoparticles,http://dx.doi.org/10.1080/21645515.2017.1369639,PMC5703362,,,"Dengue virus (DV) is the etiologic agent of dengue fever, the most significant mosquito-borne viral disease in humans. Most DV vaccine approaches are focused on generating antibody mediated responses; one such DV vaccine is approved for use in humans but its efficacy is limited. While it is clear that T cell responses play important role in DV infection and subsequent disease manifestations, fewer studies are aimed at developing vaccines that induce robust T cells responses. Potent T cell based vaccines require 2 critical components: the identification of specific T cell stimulating MHC associated peptides, and an optimized vaccine delivery vehicle capable of simultaneously delivering the antigens and any required adjuvants. We have previously identified and characterized DV specific HLA-A2 and -A24 binding DV serotypes conserved epitopes, and the feasibility of an epitope based vaccine for DV infection. In this study, we build on those previous studies and describe an investigational DV vaccine using T cell epitopes incorporated into a calcium phosphate nanoparticle (CaPNP) delivery system. This study presents a comprehensive analysis of functional immunogenicity of DV CaPNP/multipeptide formulations in vitro and in vivo and demonstrates the CaPNP/multipeptide vaccine is capable of inducing T cell responses against all 4 serotypes of DV. This synthetic vaccine is also cost effective, straightforward to manufacture, and stable at room temperature in a lyophilized form. This formulation may serve as an effective candidate DV vaccine that protects against all 4 serotypes as either a prophylactic or therapeutic vaccine.",,"['Huang, Xiaofang', 'Karabudak, Aykan', 'Comber, Joseph D.', 'Philip, Mohan', 'Morcol, Tulin', 'Philip, Ramila']",,,,
,PMC,Airway ciliary dysfunction: Association with adverse postoperative outcomes in non-heterotaxy congenital heart disease patients,http://dx.doi.org/10.1016/j.jtcvs.2017.09.050,PMC6422347,,,"OBJECTIVE: Heterotaxy (HTX) congenital heart disease (CHD) patients with ciliary dysfunction (CD) have been shown to have increased postoperative respiratory morbidity. We hypothesized that non-HTX CHD infants with CD will also have increased postoperative morbidity, particularly respiratory complications. METHODS: Sixty-three infants with non-HTX CHD undergoing cardiac surgery were enrolled. Tests commonly used to assess for CD, nasal nitric oxide (nNO) measurements and nasal epithelial ciliary motion (CM) assessment, were obtained. Baseline characteristics and postoperative outcomes were collected and analyzed. RESULTS: Non-HTX CHD infants exhibited a high prevalence of abnormal CM (32%) and low nNO (39%). This was not correlated with demographics or surgical complexity. Infants with abnormal CM had increased odds of requiring non-invasive positive pressure ventilation (OR 6.5, CI 1.5–29.4, P = 0.016) and respiratory medication use (OR 4.4, CI 1.5–13.3, P = 0.01). In contrast, infants with low nNO showed evidence of abnormal pre- and postoperative systolic function (40% vs. 4%; P = 0.004, and 34% vs. 13%; P = 0.056, respectively) and had higher odds of acquiring infections (OR 4.9, CI 1.4–17, P = 0.014). CONCLUSIONS: Non-HTX CHD infants with abnormal CM showed increased postoperative morbidity associated with poor respiratory outcomes. In contrast, low nNO correlated with reduced hemodynamic function. These findings suggest screening for abnormal CM may allow perioperative interventions to reduce pulmonary morbidities. Whether low nNO may prognosticate poor hemodynamic function warrants further investigation.",,"['Stewart, Eileen', 'Adams, Phillip S.', 'Tian, Xin', 'Khalifa, Omar', 'Wearden, Peter', 'Zahid, Maliha', 'Lo, Cecilia W.']",,,,
,PMC,Intrarenal Angiotensin-Converting Enzyme: the Old and the New,http://dx.doi.org/10.1007/s11906-017-0778-2,PMC5913745,,,"PURPOSE OF REVIEW: The intrarenal renin-angiotensin-aldosterone system (RAS) is an independent paracrine hormonal system with an increasingly prominent role in hypertension and renal disease. Two enzyme components of this system are angiotensin-converting enzyme (ACE) and more recently discovered ACE2. The purpose of this review is to describe recent discoveries regarding the roles of intrarenal ACE and ACE2 and their interaction. RECENT FINDINGS: Renal tubular ACE contributes to salt-sensitive hypertension. Additionally, the relative expression and activity of intrarenal ACE and ACE2 are central to promoting or inhibiting different renal pathologies including renovascular hypertension, diabetic nephropathy, and renal fibrosis. SUMMARY: Renal ACE and ACE2 represent two opposing axes within the intrarenal RAS system whose interaction determines the progression of several common disease processes. While this relationship remains complex and incompletely understood, further investigations hold the potential for creating novel approaches to treating hypertension and kidney disease.",,"['Culver, Silas', 'Li, Caixia', 'Siragy, Helmy M.']",,,,
,PMC,Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein,http://dx.doi.org/10.1073/pnas.1712592114,PMC5635925,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) targets the epithelial cells of the respiratory tract both in humans and in its natural host, the dromedary camel. Virion attachment to host cells is mediated by 20-nm-long homotrimers of spike envelope protein S. The N-terminal subunit of each S protomer, called S1, folds into four distinct domains designated S1(A) through S1(D). Binding of MERS-CoV to the cell surface entry receptor dipeptidyl peptidase 4 (DPP4) occurs via S1(B). We now demonstrate that in addition to DPP4, MERS-CoV binds to sialic acid (Sia). Initially demonstrated by hemagglutination assay with human erythrocytes and intact virus, MERS-CoV Sia-binding activity was assigned to S subdomain S1(A). When multivalently displayed on nanoparticles, S1 or S1(A) bound to human erythrocytes and to human mucin in a strictly Sia-dependent fashion. Glycan array analysis revealed a preference for α2,3-linked Sias over α2,6-linked Sias, which correlates with the differential distribution of α2,3-linked Sias and the predominant sites of MERS-CoV replication in the upper and lower respiratory tracts of camels and humans, respectively. Binding is hampered by Sia modifications such as 5-N-glycolylation and (7,)9-O-acetylation. Depletion of cell surface Sia by neuraminidase treatment inhibited MERS-CoV entry of Calu-3 human airway cells, thus providing direct evidence that virus–Sia interactions may aid in virion attachment. The combined observations lead us to propose that high-specificity, low-affinity attachment of MERS-CoV to sialoglycans during the preattachment or early attachment phase may form another determinant governing the host range and tissue tropism of this zoonotic pathogen.",,"['Li, Wentao', 'Hulswit, Ruben J. G.', 'Widjaja, Ivy', 'Raj, V. Stalin', 'McBride, Ryan', 'Peng, Wenjie', 'Widagdo, W.', 'Tortorici, M. Alejandra', 'van Dieren, Brenda', 'Lang, Yifei', 'van Lent, Jan W. M.', 'Paulson, James C.', 'de Haan, Cornelis A. M.', 'de Groot, Raoul J.', 'van Kuppeveld, Frank J. M.', 'Haagmans, Bart L.', 'Bosch, Berend-Jan']",,,,
,PMC,Medical Management of Hospitalized Patients with Asthma or Chronic Obstructive Pulmonary Disease,http://dx.doi.org/10.1016/j.ehmc.2017.05.002,PMC6289537,,,,,"['Duong, Theresa N.', 'Zeki, Amir A.', 'Louie, Samuel']",,,,
,PMC,Intrahost selection pressures drive rapid dengue virus microevolution in acute human infections,http://dx.doi.org/10.1016/j.chom.2017.08.003,PMC5616187,,,"Dengue, caused by four dengue virus serotypes (DENV-1–DENV-4), is a highly-prevalent mosquito-borne viral disease in humans. Yet, selection pressures driving DENV microevolution within human hosts (‘intrahost’) remain unknown. We employed a whole-genome segmented amplification approach coupled with deep sequencing to profile DENV-3 intrahost diversity in peripheral blood mononuclear cell (PBMC) and plasma samples from 77 dengue patients. DENV-3 intrahost diversity appears to be driven by immune pressures as well as replicative success in PBMCs and potentially other replication sites. Hotspots for intrahost variation were detected in 59–78% of patients in the viral Envelope and pre-Membrane/Membrane proteins, which together form the virion surface. Dominant variants at the hotspots arose via convergent microevolution, appear to be immune-escape variants, and were evolutionarily constrained at the macro-level due to viral replication defects. Dengue is thus an example of an acute infection in which selection pressures within infected individuals drive rapid intrahost virus microevolution.",,"['Parameswaran, Poornima', 'Wang, Chunling', 'Trivedi, Surbhi Bharat', 'Eswarappa, Meghana', 'Montoya, Magelda', 'Balmaseda, Angel', 'Harris, Eva']",,,,
,PMC,Simian varicella virus inhibits the interferon gamma signalling pathway,http://dx.doi.org/10.1099/jgv.0.000925,PMC5845570,,,"The alphaherpesvirus simian varicella virus (SVV) causes varicella and zoster in nonhuman primates. Herpesviruses evolved elaborate mechanisms to escape host immunity, but the immune evasion strategies employed by SVV remain ill-defined. We analysed whether SVV impairs the cellular response to key antiviral cytokine interferon-γ (IFNγ). SVV infection inhibited the expression of IFNγ-induced genes like C-X-C motif chemokine 10 and interferon regulatory factor 1. Phosphorylation and nuclear translocation of the signal transducer and activator of transcription 1 (STAT1) was blocked in SVV-infected cells, which did not involve cellular and viral phosphatases. SVV infection did not downregulate IFNγ receptor α and β chain expression on the cell surface. Instead, STAT1, Janus tyrosine kinases 1 (JAK1) and JAK2 protein levels were significantly decreased in SVV-infected cells. Collectively, these results demonstrate that SVV targets three proteins in the IFNγ signal transduction pathway to escape the antiviral effects of IFNγ.",,"['Ouwendijk, Werner J. D.', 'van Veen, Suzanne', 'Mahalingam, Ravi', 'Verjans, Georges M. G. M.']",,,,
,PMC,Polyamines and Their Role in Virus Infection,http://dx.doi.org/10.1128/MMBR.00029-17,PMC5706744,,,"Polyamines are small, abundant, aliphatic molecules present in all mammalian cells. Within the context of the cell, they play a myriad of roles, from modulating nucleic acid conformation to promoting cellular proliferation and signaling. In addition, polyamines have emerged as important molecules in virus-host interactions. Many viruses have been shown to require polyamines for one or more aspects of their replication cycle, including DNA and RNA polymerization, nucleic acid packaging, and protein synthesis. Understanding the role of polyamines has become easier with the application of small-molecule inhibitors of polyamine synthesis and the use of interferon-induced regulators of polyamines. Here we review the diverse mechanisms in which viruses require polyamines and investigate blocking polyamine synthesis as a potential broad-spectrum antiviral approach.",,"['Mounce, Bryan C.', 'Olsen, Michelle E.', 'Vignuzzi, Marco', 'Connor, John H.']",,,,
,PMC,"Monoclonal Antibodies, Derived from Humans Vaccinated with the RV144 HIV Vaccine Containing the HVEM Binding Domain of Herpes Simplex Virus (HSV) Glycoprotein D, Neutralize HSV Infection, Mediate Antibody-Dependent Cellular Cytotoxicity, and Protect Mice from Ocular Challenge with HSV-1",http://dx.doi.org/10.1128/JVI.00411-17,PMC5599770,,,"The RV144 HIV vaccine trial included a recombinant HIV glycoprotein 120 (gp120) construct fused to a small portion of herpes simplex virus 1 (HSV-1) glycoprotein D (gD) so that the first 40 amino acids of gp120 were replaced by the signal sequence and the first 27 amino acids of the mature form of gD. This region of gD contains most of the binding site for HVEM, an HSV receptor important for virus infection of epithelial cells and lymphocytes. RV144 induced antibodies to HIV that were partially protective against infection, as well as antibodies to HSV. We derived monoclonal antibodies (MAbs) from peripheral blood B cells of recipients of the RV144 HIV vaccine and showed that these antibodies neutralized HSV-1 infection in cells expressing HVEM, but not the other major virus receptor, nectin-1. The MAbs mediated antibody-dependent cellular cytotoxicity (ADCC), and mice that received the MAbs and were then challenged by corneal inoculation with HSV-1 had reduced eye disease, shedding, and latent infection. To our knowledge, this is the first description of MAbs derived from human recipients of a vaccine that specifically target the HVEM binding site of gD. In summary, we found that monoclonal antibodies derived from humans vaccinated with the HVEM binding domain of HSV-1 gD (i) neutralized HSV-1 infection in a cell receptor-specific manner, (ii) mediated ADCC, and (iii) reduced ocular disease in virus-infected mice. IMPORTANCE Herpes simplex virus 1 (HSV-1) causes cold sores and neonatal herpes and is a leading cause of blindness. Despite many trials, no HSV vaccine has been approved. Nectin-1 and HVEM are the two major cellular receptors for HSV. These receptors are expressed at different levels in various tissues, and the role of each receptor in HSV pathogenesis is not well understood. We derived human monoclonal antibodies from persons who received the HIV RV144 vaccine that contained the HVEM binding domain of HSV-1 gD fused to HIV gp120. These antibodies were able to specifically neutralize HSV-1 infection in vitro via HVEM. Furthermore, we showed for the first time that HVEM-specific HSV-1 neutralizing antibodies protect mice from HSV-1 eye disease, indicating the critical role of HVEM in HSV-1 ocular infection.",,"['Wang, Kening', 'Tomaras, Georgia D.', 'Jegaskanda, Sinthujan', 'Moody, M. Anthony', 'Liao, Hua-Xin', 'Goodman, Kyle N.', 'Berman, Phillip W.', 'Rerks-Ngarm, Supachai', 'Pitisuttithum, Punnee', 'Nitayapan, Sorachai', 'Kaewkungwal, Jaranit', 'Haynes, Barton F.', 'Cohen, Jeffrey I.']",,,,
,PMC,Permissivity of Dipeptidyl Peptidase 4 Orthologs to Middle East Respiratory Syndrome Coronavirus Is Governed by Glycosylation and Other Complex Determinants,http://dx.doi.org/10.1128/JVI.00534-17,PMC5599747,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes dipeptidyl peptidase 4 (DPP4) as an entry receptor. While bat, camel, and human DPP4 support MERS-CoV infection, several DPP4 orthologs, including mouse, ferret, hamster, and guinea pig DPP4, do not. Previous work revealed that glycosylation of mouse DPP4 plays a role in blocking MERS-CoV infection. Here, we tested whether glycosylation also acts as a determinant of permissivity for ferret, hamster, and guinea pig DPP4. We found that, while glycosylation plays an important role in these orthologs, additional sequence and structural determinants impact their ability to act as functional receptors for MERS-CoV. These results provide insight into DPP4 species-specific differences impacting MERS-CoV host range and better inform our understanding of virus-receptor interactions associated with disease emergence and host susceptibility. IMPORTANCE MERS-CoV is a recently emerged zoonotic virus that is still circulating in the human population with an ∼35% mortality rate. With no available vaccines or therapeutics, the study of MERS-CoV pathogenesis is crucial for its control and prevention. However, in vivo studies are limited because MERS-CoV cannot infect wild-type mice due to incompatibilities between the virus spike and the mouse host cell receptor, mouse DPP4 (mDPP4). Specifically, mDPP4 has a nonconserved glycosylation site that acts as a barrier to MERS-CoV infection. Thus, one mouse model strategy has been to modify the mouse genome to remove this glycosylation site. Here, we investigated whether glycosylation acts as a barrier to infection for other nonpermissive small-animal species, namely, ferret, guinea pig, and hamster. Understanding the virus-receptor interactions for these DPP4 orthologs will help in the development of additional animal models while also revealing species-specific differences impacting MERS-CoV host range.",,"['Peck, Kayla M.', 'Scobey, Trevor', 'Swanstrom, Jesica', 'Jensen, Kara L.', 'Burch, Christina L.', 'Baric, Ralph S.', 'Heise, Mark T.']",,,,
,PMC,Role of the inflammasome-related cytokines Il-1 and Il-18 during infection with murine coronavirus,http://dx.doi.org/10.1007/s13365-017-0574-4,PMC5726909,,,"The inflammasome, a cytosolic protein complex that mediates the processing and secretion of pro-inflammatory cytokines, is one of the first responders during viral infection. The cytokines secreted following inflammasome activation, which include IL-1 and IL-18, regulate cells of both the innate and adaptive immune system, guiding the subsequent immune responses. In this study we used murine coronavirus, mouse hepatitis virus (MHV), infection of the central nervous system and liver to assess of the role of the inflammasome and its related cytokines on pathogenesis and host defense during viral infection. Mice lacking all inflammasome signaling due to the absence of caspase-1 and -11 were more vulnerable to infection, with poor survival and elevated viral replication compared to wild type mice. Mice lacking IL-1 signaling experienced elevated viral replication but similar survival compared to wild type controls. In the absence of IL-18, mice had elevated viral replication and poor survival, and this protective effect of IL-18 was found to be due to promotion of interferon gamma production in αβ T cells. These data suggest that inflammasome signaling is largely protective during murine coronavirus infection, in large part due to the pro-inflammatory effects of IL-18.",,"['Zalinger, Zachary B.', 'Elliott, Ruth', 'Weiss, Susan R.']",,,,
,PMC,Tissue compartmentalization of T cell responses during early life,http://dx.doi.org/10.1007/s00281-017-0648-7,PMC5743209,,,"The immune system in early life is tasked with transitioning from a relatively protected environment to one in which it encounters a wide variety of innocuous antigens and dangerous pathogens. The immaturity of the developing immune system, and particularly the distinct functionality of T lymphocytes in early life, has been implicated in increased susceptibility to infection. Previous work has demonstrated that immune responses in early life are skewed towards limited inflammation and atopy, however, there is mounting evidence that such responses are context-and tissue-dependent. The regulation, differentiation and maintenance of infant T cell responses, particularly as it relates to tissue compartmentalization, remains poorly understood. How the tissue environment impacts early life immune responses and whether the development of localized protective immune memory cell subsets are established is an emerging area of research. As infectious diseases affecting the respiratory and digestive tracts are a leading cause of morbidity and mortality worldwide in infants and young children, a deeper understanding of site specific immunity is essential to addressing these challenges. Here we review the current paradigms of T cell responses during infancy as they relate to tissue localization and discuss implications for the development of vaccines and therapeutics.",,"['Zens, Kyra D.', 'Connors, Thomas', 'Farber, Donna L.']",,,,
,PMC,Public Health and Epidemiology Informatics,http://dx.doi.org/10.15265/IY-2017-036,PMC6239244,,,"Objectives: To summarize current research in the field of Public Health and Epidemiology Informatics. Methods : The complete 2016 literature concerning public health and epidemiology informatics has been searched in PubMed and Web of Science, and the returned references were reviewed by the two section editors to select 14 candidate best papers. These papers were then peer-reviewed by external reviewers to allow the editorial team an enlightened selection of the best papers. Results : Among the 829 references retrieved from PubMed and Web of Science, three were finally selected as best papers. The first one compares Google, Twitter, and Wikipedia as tools for Influenza surveillance. The second paper presents a Geographic Knowledge-Based Model for mapping suitable areas for Rift Valley fever transmission in Eastern Africa. The last paper evaluates the factors associated with the visit of Facebook pages devoted to Public Health Communication. Conclusions: Surveillance is still a productive topic in public health informatics but other very important topics in public health are appearing.",,"['Thiébaut, R.', 'Thiessard, F.', None]",,,,
,PMC,Airway epithelial barrier dysfunction in the pathogenesis and prognosis of respiratory tract diseases in childhood and adulthood,http://dx.doi.org/10.1080/21688370.2017.1367458,PMC5788424,,,"The lungs are in direct contact with the environment through the tubular structure that constitutes the airway. Starting from the nasal orifice, the airway is exposed to foreign particles including infectious agents, allergens, and other substances that can damage the airways. Therefore, the airway must have a functional epithelial barrier both in the upper and lower airways to protect against these threats. As with the skin, it is likely that the pathogenesis of respiratory diseases is a consequence of epithelial barrier defects in these airways. The characteristics of this system, starting from the beginning of life and extending into maturing and aging, determine the prognosis of respiratory diseases. In this article, we discuss the pathogenesis, clinical phenotype, and prognosis of respiratory diseases from newborns to adulthood in the context of epithelial barrier function and dysfunction.",,"['Yuksel, Hasan', 'Turkeli, Ahmet']",,,,
,PMC,Conference report: the 5th Asia Pacific Protein Association Conference joint meeting with the 12th International Symposium of the Protein Society of Thailand,http://dx.doi.org/10.1007/s12551-017-0318-y,PMC5711698,,,,,"['Ketudat Cairns, James R.', 'Champattanachai, Voraratt', 'Srisomsap, Chantragan', 'Paricharttanakul, N. Monique', 'Verathamjamras, Chris', 'Lirdprapamongkol, Kriengsak', 'Svasti, Jisnuson']",,,,
,PMC,"Knowledge, perceptions and practices of healthcare workers regarding the use of respiratory protection equipment at Iran hospitals",http://dx.doi.org/10.1177/1757177417724880,PMC5753949,,,"BACKGROUND: Using appropriate respiratory protection equipment (RPE) is very important to protect healthcare workers (HCWs) against respiratory hazards. The aim of this study was to identify the level of knowledge, perceptions and practices of HCWs on using RPE. METHODS: This cross-sectional study was conducted with 284 employees of educational hospitals affiliated to Shiraz University of Medical Sciences. The study’s instrument was a self-made questionnaire that comprised four components: demographic inquiries and questions designed to assess the knowledge, perceptions and practice of HCWs regarding RPE. Collected data were analysed using SPSS software version 21. RESULTS: Average scores of knowledge, perceptions and practice of HCWs on using RPE were 66.50% ± 11.93%, 80.32% ± 10.05% and 70.12% ± 20.51%, respectively. A significant association was observed between knowledge and age, job experience, history of using respirator, marital status and risk of respiratory hazards in the workplace and perceptions with age and education and practice with education. CONCLUSION: Studied HCWs had positive perceptions and moderate level of knowledge and practice about the use of RPE. Full implementation of respiratory protection program in the hospitals would be helpful to improve the knowledge, perceptions and practices of HCWs regarding RPE.",,"['Honarbakhsh, Marzieh', 'Jahangiri, Mehdi', 'Ghaem, Haleh']",,,,
,PMC,Undiagnosed Active Pulmonary Tuberculosis among Pilgrims during the 2015 Hajj Mass Gathering: A Prospective Cross-sectional Study,http://dx.doi.org/10.4269/ajtmh.17-0271,PMC5817770,,,"Mass gatherings pose a risk for tuberculosis (TB) transmission and reactivation of latent TB infection. The annual Hajj pilgrimage attracts 2 million pilgrims many from high TB-endemic countries. We evaluated the burden of undiagnosed active pulmonary TB in pilgrims attending the 2015 Hajj mass gathering. We conducted a prospective cross-sectional study in Mecca, Kingdom of Saudi Arabia, for nonhospitalized adult pilgrims from five high TB-endemic countries. Enrollment criteria were the presence of a cough and the ability to produce a sputum sample. Sputum samples were processed using the Xpert MTB-RIF assay. Data were analyzed for drug-resistant TB, risk factors, and comorbidities by the country of origin. Of 1,164 consenting pilgrims enrolled from five countries: Afghanistan (316), Bangladesh (222), Nigeria (176), Pakistan (302), and South Africa (148), laboratory results were available for 1,063 (91.3%). The mean age of pilgrims was 54.5 (range = 18–94 years) with a male to female ratio of 2.6:1; 27.7% had an underlying comorbidity, with hypertension and diabetes being the most common, 20% were smokers, and 2.8% gave a history of previous TB treatment. Fifteen pilgrims (1.4%) had active previously undiagnosed drug-sensitive pulmonary TB (Afghanistan [12; 80%], Pakistan [2; 13.3%], and Nigeria [1; 6.7%]). No multidrug-resistant TB cases were detected. Pilgrims from high TB-endemic Asian and African countries with undiagnosed active pulmonary TB pose a risk to other pilgrims from over 180 countries. Further studies are required to define the scale of the TB problem during the Hajj mass gathering and the development of proactive screening, treatment and prevention guidelines.",,"['Yezli, Saber', 'Zumla, Alimuddin', 'Yassin, Yara', 'Al-Shangiti, Ali M.', 'Mohamed, Gamal', 'Turkistani, Abdulhafiz M.', 'Alotaibi, Badriah']",,,,
,PMC,"Incidence, Risks, and Types of Infections in Pediatric Long-term Care Facilities",http://dx.doi.org/10.1001/jamapediatrics.2017.1482,PMC5710407,,,"IMPORTANCE: The population of infants, children, and adolescents cared for at pediatric long-term care facilities is increasing in complexity and size and thus consumes substantial health care resources. Infections are a significant cause of morbidity and mortality in this population, but few recent data describe their incidence and effects. OBJECTIVES: To describe the types of infections diagnosed in residents of pediatric long-term care facilities, calculate infection rates, and identify risk factors for respiratory tract infections (RTIs). DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study, which was part of a larger trial called Keep It Clean for Kids, was conducted from September 1, 2012, to December 31, 2015, at 3 pediatric long-term care facilities in New York. Residents of the facilities who were 21 years or younger and either residents or admitted during the study period (n = 717) were enrolled in the study. Medical records were reviewed to identify infections diagnosed by site clinicians. MAIN OUTCOMES AND MEASURES: Incidence of infections, such as RTIs; skin and soft-tissue infections; chronic comorbid conditions, including neurologic and respiratory disorders; and device use, including gastrostomy tubes and tracheostomies, was determined. Risk factors for RTIs were assessed by generalized linear mixed method regression modeling. RESULTS: The 717 residents had a median (interquartile range) age at enrollment of 2.6 (0.4-9.1) years; 358 (49.9%) were male. Four hundred twenty-eight residents (59.7%) had feeding tubes and 215 (30.0%) had tracheostomies. Most chronic comorbid conditions were musculoskeletal or ambulation (532 residents [74.2%]), neurologic (505 [70.4%]), respiratory (361 [50.3%]), and gastrointestinal (230 [32.1%]) disorders, and 460 residents (64.2%) had 4 or more chronic comorbid conditions. Site clinicians diagnosed 2052 infections during the 3-year study period. Respiratory tract infections were most common and were diagnosed in 1291 residents (62.9%). The overall infection rate was 5.3 infections per 1000 resident-days, and RTI rates were 3.3 infections per 1000 resident-days. Overall infection rates and rates of RTI, skin and soft-tissue infection, urinary tract infection, and bloodstream infection varied among the 3 sites. In the multivariable model, younger age (incidence rate ratio [IRR], 1.05; 95% CI, 1.03-1.06), increased number of chronic comorbid conditions (IRR, 1.12; 95% CI, 1.06-1.19), and the use of feeding tubes (IRR, 1.34; 95% CI, 1.03-1.64) and tracheostomies (IRR, 1.40; 95% CI, 1.17-1.69) were associated with RTIs. CONCLUSIONS AND RELEVANCE: In this study, RTIs were the most common infections diagnosed, but modifiable risk factors for RTIs were not identified. Future work should focus on optimizing infection prevention and control strategies to reduce infections, particularly RTIs, in the pediatric long-term care population.",,"['Saiman, Lisa', 'Maykowski, Philip', 'Murray, Meghan', 'Cohen, Bevin', 'Neu, Natalie', 'Jia, Haomioa', 'Hutcheon, Gordon', 'Simpser, Edwin', 'Mosiello, Linda', 'Alba, Luis', 'Larson, Elaine']",,,,
,PMC,Structure of the Ebola virus envelope protein MPER/TM domain and its interaction with the fusion loop explains their fusion activity,http://dx.doi.org/10.1073/pnas.1708052114,PMC5617291,,,"Ebolavirus (EBOV), an enveloped filamentous RNA virus causing severe hemorrhagic fever, enters cells by macropinocytosis and membrane fusion in a late endosomal compartment. Fusion is mediated by the EBOV envelope glycoprotein GP, which consists of subunits GP1 and GP2. GP1 binds to cellular receptors, including Niemann-Pick C1 (NPC1) protein, and GP2 is responsible for low pH-induced membrane fusion. Proteolytic cleavage and NPC1 binding at endosomal pH lead to conformational rearrangements of GP2 that include exposing the hydrophobic fusion loop (FL) for insertion into the cellular target membrane and forming a six-helix bundle structure. Although major portions of the GP2 structure have been solved in pre- and postfusion states and although current models place the transmembrane (TM) and FL domains of GP2 in close proximity at critical steps of membrane fusion, their structures in membrane environments, and especially interactions between them, have not yet been characterized. Here, we present the structure of the membrane proximal external region (MPER) connected to the TM domain: i.e., the missing parts of the EBOV GP2 structure. The structure, solved by solution NMR and EPR spectroscopy in membrane-mimetic environments, consists of a helix-turn-helix architecture that is independent of pH. Moreover, the MPER region is shown to interact in the membrane interface with the previously determined structure of the EBOV FL through several critical aromatic residues. Mutation of aromatic and neighboring residues in both binding partners decreases fusion and viral entry, highlighting the functional importance of the MPER/TM–FL interaction in EBOV entry and fusion.",,"['Lee, Jinwoo', 'Nyenhuis, David A.', 'Nelson, Elizabeth A.', 'Cafiso, David S.', 'White, Judith M.', 'Tamm, Lukas K.']",,,,
,PMC,PNAS Plus Significance Statements,http://dx.doi.org/10.1073/pnas.ss11440,PMC5635945,,,,,,,,,
,PMC,A Conceptual Framework for the Evaluation of Emergency Risk Communications,http://dx.doi.org/10.2105/AJPH.2017.304040,PMC5594401,,,"Objectives. To articulate a conceptual framework in support of evaluation activities in emergency risk communications (ERC). Methods. The framework proposed is based on a systematic review of the scientific literature (2001–2016) combined with data derived from a series of semistructured interviews with experts and practitioners in ERC, and it is designed to support local, national, and international public health organizations in implementing evaluation studies in ERC. Results. We identified a list of ERC outcomes from the full-text review of 152 articles and categorized these into 3 groups, depending upon the level at which the outcome was measured: (1) information environment, (2) population, and (3) public health system. We analyzed interviewees’ data from 18 interviews to identify practices and processes related to the effectiveness of ERC and included these as key structural components and processes in the developed evaluation framework. Conclusions. Researchers and public health practitioners interested in the evaluation of ERC can use the conceptual framework described in this article to guide the development of evaluation studies and methods for assessing communication outcomes related to public health emergencies.",,"['Savoia, Elena', 'Lin, Leesa', 'Gamhewage, Gaya M.']",,,,
,PMC,Public Health Preparedness Funding: Key Programs and Trends From 2001 to 2017,http://dx.doi.org/10.2105/AJPH.2017.303963,PMC5594397,,,"Objectives. To evaluate trends in funding over the past 16 years for key federal public health preparedness and response programs at the US Department of Health and Human Services, to improve understanding of federal funding history in this area, and to provide context for future resource allocation decisions for public health preparedness. Methods. In this 2017 analysis, we examined the funding history of key federal programs critical to public health preparedness by reviewing program budget data collected for our annual examination of federal funding for biodefense and health security programs since fiscal year (FY) 2001. Results. State and local preparedness at the Centers for Disease Control and Prevention initially received $940 million in FY2002 and resulted in significant preparedness gains, but funding levels have since decreased by 31%. Similarly, the Hospital Preparedness Program within the Office of the Assistant Secretary for Preparedness and Response was funded at a high of $515 million in FY2003, but funding was reduced by 50%. Investments in medical countermeasure development and stockpiling remained relatively stable. Conclusions. The United States has made significant progress in preparing for disasters and advancing public health infrastructure. To enable continued advancement, federal funding commitments must be sustained.",,"['Watson, Crystal R.', 'Watson, Matthew', 'Sell, Tara Kirk']",,,,
,PMC,Applying the 15 Public Health Emergency Preparedness Capabilities to Support Large-Scale Tuberculosis Investigations in Complex Congregate Settings,http://dx.doi.org/10.2105/AJPH.2017.303946,PMC5594386,,,"Public Health—Seattle and King County, a metropolitan health department in western Washington, experiences rates of tuberculosis (TB) that are 1.6 times higher than are state and national averages. The department’s TB Control Program uses public health emergency management tools and capabilities sustained with Centers for Disease Control and Prevention grant funding to manage large-scale complex case investigations. We have described 3 contact investigations in large congregate settings that the TB Control Program conducted in 2015 and 2016. The program managed the investigations using public health emergency management tools, with support from the Preparedness Program. The 3 investigations encompassed medical evaluation of more than 1600 people, used more than 100 workers, identified nearly 30 individuals with latent TB infection, and prevented an estimated 3 cases of active disease. These incidents exemplify how investments in public health emergency preparedness can enhance health outcomes in traditional areas of public health.",,"['Levy, Alison Jaffe', 'Toren, Katelynne Gardner', 'Elsenboss, Carina', 'Narita, Masahiro']",,,,
,PMC,An Unusual Cause of Fever in a Patient with Common Variable Immunodeficiency,http://dx.doi.org/10.1016/j.anai.2017.07.003,PMC5672827,,,,,"['Dang, Andrew T.', 'Schwartz, Gene', 'Jones, LaQuita', 'Absalon, Michael J.', 'McMasters, Richard L.', 'Assa’ad, Amal']",,,,
,PMC,Emerging Infectious Diseases: Epidemiological Perspective,http://dx.doi.org/10.4103/ijd.IJD_379_17,PMC5618832,28979007,CC BY-NC-SA,"Over the past 30 years, at least 30 new infectious diseases have emerged to threaten the health of millions of people across the globe. The major challenge to combat these infections is that for many of them, there is no specific treatment or cure or vaccine. There is limited scope of preventing or controlling them. The contributory factors include urbanization and destruction of natural habitats, climate change and changing ecosystems, changes in population of reservoir hosts or intermediate insect vectors and microbial genetic mutation, international trade and commerce, change in human demographics and behavior, lack of public health services and infrastructure, and antibiotic resistance. It is clear by now that the problem of emerging infectious disease (EID) is not restricted to any single country, and a strong and sustainable international collaboration will be needed in their prevention and control. India along with other countries in the South-East Asian region will continue to bear the brunt of the burden of EIDs in years to come.",2017 Sep-Oct,"Mukherjee, Shuvankar",Indian J Dermatol,,,
,PMC,Emerging and Re-emerging Infectious Diseases in South East Asia,http://dx.doi.org/10.4103/ijd.IJD_389_17,PMC5618830,28979005,CC BY-NC-SA,,2017 Sep-Oct,"Sarma, Nilendu",Indian J Dermatol,,,
,PMC,High Containment Pathogen Preparation in the Intensive Care Unit,http://dx.doi.org/10.1016/j.idc.2017.05.008,PMC5568084,,,"The recent Ebola virus disease outbreak highlighted the need to build national and worldwide capacity to provide care for patients with highly infectious diseases. Specialized biocontainment units were successful in treating a number of critically ill patients with Ebola virus disease both in the United States and Europe. Several key principles underlie the care of critically ill patients in a high containment environment. Environmental factors, staffing, equipment, training, laboratory testing, procedures and waste management each present unique challenges. A multidisciplinary approach is key to developing effective systems and protocols to maintain the safety of patients, staff and communities.",,"['Garibaldi, Brian T.', 'Chertow, Daniel S.']",,,,
,PMC,Abstracts of Scientific Presentations,,PMC5605184,,,,,,,,,
,PMC,Quantification of Induced Hypothermia from Aseptic Scrub Applications during Rodent Surgery Preparation,,PMC5605182,,,"Laboratory mice (Mus musculus) are prone to develop hypothermia during anesthesia for surgery, thus potentially impeding anesthetic recovery, wound healing, and future health. The core body temperatures of isoflurane-anesthetized mice are influenced by the choice of supplemental heat sources; however, the contribution of various surgical scrubs on the body temperatures of mice under gas anesthesia has not been assessed. We sought to quantify the effect of using alcohol (70% isopropyl alcohol [IPA]) compared with saline to rinse away surgical scrub on the progression of hypothermia in anesthetized mice (n = 47). IPA, room-temperature saline, or warmed saline (37 °C) was combined with povidone–iodine and then assessed for effects on core (rectal) and surface (infrared) temperatures. Agents were applied to a 2×2-cm shaved abdominal area of mice maintained on a water-recirculating blanket (at 38 °C) under isoflurane anesthesia (1.5% to 2.0% at 0.6 L/min) for 30 min. Although all scrub regimens significantly decreased body temperature at the time of application, treatments that included povidone–iodine led to the coldest core temperatures, which persisted while mice were anesthetized. Compared with room-temperature saline and when combined with povidone–iodine, warming of saline did not ameliorate heat loss. IPA alone demonstrated the most dramatic cooling of both surface and core readings at application but generated an unanticipated warming (rebound) phase during which body temperatures equilibrated with those of controls within minutes of application. Although alcohol is inappropriate as a stand-alone agent for surgical skin preparation, IPA is a viable alternative to saline-based rinses in this context, and its use should be encouraged within institutional guidance for rodent surgical procedures without concern for prolonged hypothermia in mice.",,"['Skorupski, Anna M', 'Zhang, Jingyi', 'Ferguson, Danielle', 'Lawrence, Frank', 'Hankenson, F Claire']",,,,
,PMC,"Laboratory-based respiratory virus surveillance pilot project on select cruise ships in Alaska, 2013–15()",http://dx.doi.org/10.1093/jtm/tax069,PMC5684694,,,"BACKGROUND: Influenza outbreaks can occur among passengers and crews during the Alaska summertime cruise season. Ill travellers represent a potential source for introduction of novel or antigenically drifted influenza virus strains to the United States. From May to September 2013–2015, the Alaska Division of Public Health, the Centers for Disease Control and Prevention (CDC), and two cruise lines implemented a laboratory-based public health surveillance project to detect influenza and other respiratory viruses among ill crew members and passengers on select cruise ships in Alaska. METHODS: Cruise ship medical staff collected 2–3 nasopharyngeal swab specimens per week from passengers and crew members presenting to the ship infirmary with acute respiratory illness (ARI). Specimens were tested for respiratory viruses at the Alaska State Virology Laboratory (ASVL); a subset of specimens positive for influenza virus were sent to CDC for further antigenic characterization. RESULTS: Of 410 nasopharyngeal specimens, 83% tested positive for at least one respiratory virus; 71% tested positive for influenza A or B virus. Antigenic characterization of pilot project specimens identified strains matching predominant circulating seasonal influenza virus strains, which were included in the northern or southern hemisphere influenza vaccines during those years. Results were relatively consistent across age groups, recent travel history, and influenza vaccination status. Onset dates of illness relative to date of boarding differed between northbound (occurring later in the voyage) and southbound (occurring within the first days of the voyage) cruises. CONCLUSIONS: The high yield of positive results indicated that influenza was common among passengers and crews sampled with ARI. This finding reinforces the need to bolster influenza prevention and control activities on cruise ships. Laboratory-based influenza surveillance on cruise ships may augment inland influenza surveillance and inform control activities. However, these benefits should be weighed against the costs and operational limitations of instituting laboratory-based surveillance programs on ships.",,"['Rogers, Kimberly B.', 'Roohi, Shahrokh', 'Uyeki, Timothy M.', 'Montgomery, David', 'Parker, Jayme', 'Fowler, Nisha H.', 'Xu, Xiyan', 'Ingram, Deandra J.', 'Fearey, Donna', 'Williams, Steve M.', 'Tarling, Grant', 'Brown, Clive M.', 'Cohen, Nicole J.']",,,,
,PMC,Pertussis and Pertussis like Illness: Pediatric Experience in Oman,http://dx.doi.org/10.5001/omj.2017.75,PMC5632702,,,"OBJECTIVES: A resurgence of pertussis or whooping cough has been observed worldwide despite broad vaccination coverage. Pertussis like illness (PLI) refers to a clinical syndrome compatible with pertussis infection but lacking laboratory confirmation or an epidemiological link to a confirmed case. Our study aimed to estimate the contribution of Bordetella pertussis infection and identifying predictors of its diagnosis in a cohort of children with PLI. METHODS: Demographic and clinical information were retrospectively collected from the medical records of children < 13 years old and hospitalized for PLI in two pediatric units in Oman from 1 January 2012 to 31 December 2013. The laboratory data of all cases were reviewed and confirmed cases of pertussis were identified, analyzed, and compared with non-confirmed cases. RESULTS: A total of 131 patients were enrolled in this study. The majority (95.4% [125/131]) were infants. Only 54.1% (71/131) of admitted children with PLI were tested for pertussis. The incidence of pertussis infection among the tested group was 16.9% (12/71) with a 95% confidence interval 8.2−25.6. Severe illness occurred in 56.4% (74/131) of patients, and six were confirmed to have pertussis. Pediatric intensive care unit admission was required for one confirmed case of pertussis and eight cases from the PLI group (three were negative for pertussis, and five were not tested). Receiver operator characteristic curve analysis revealed that a white blood cell count (3) 23.5 × 10(9)/L had 96.6% specificity and lymphocytes (3) 17 × 10(9)/L had 98.3% specificity. CONCLUSIONS: Taking into consideration that the number tested for pertussis was limited, the incidence of pertussis was 16.9% (12 out of 71 patients). Lymphocytosis can be used as a reliable predictor for the diagnosis of pertussis especially in the absence of specific confirmatory tests or until their results are available.",,"['Al Maani, Amal', 'Al Qayoudhi, Abdullah', 'Nazir, Hanan Fawzi', 'Omar, Heba', 'Al Jardani, Amina', 'Al Muharrmi, Zakariya', 'Wali, Yasser']",,,,
,PMC,PRINCIPLES AND PATTERNS OF BAT MOVEMENTS: FROM AERODYNAMICS TO ECOLOGY,http://dx.doi.org/10.1086/693847,PMC5983048,,,"Movement ecology as an integrative discipline has advanced associated fields because it presents not only a conceptual framework for understanding movement principles but also helps formulate predictions about the consequences of movements for animals and their environments. Here, we synthesize recent studies on principles and patterns of bat movements in context of the movement ecology paradigm. The motion capacity of bats is defined by their highly articulated, flexible wings. Power production during flight follows a U-shaped curve in relation to speed in bats yet, in contrast to birds, bats use mostly exogenous nutrients for sustained flight. The navigation capacity of most bats is dominated by the echolocation system, yet other sensory modalities, including an iron-based magnetic sense, may contribute to navigation depending on a bat’s familiarity with the terrain. Patterns derived from these capacities relate to antagonistic and mutualistic interactions with food items. The navigation capacity of bats may influence their sociality, in particular, the extent of group foraging based on eavesdropping on conspecifics’ echolocation calls. We infer that understanding the movement ecology of bats within the framework of the movement ecology paradigm provides new insights into ecological processes mediated by bats, from ecosystem services to diseases.",,"['Voigt, Christian C.', 'Frick, Winifred F.', 'Holderied, Marc W.', 'Holland, Richard', 'Kerth, Gerald', 'Mello, Marco A. R.', 'Plowright, Raina K.', 'Swartz, Sharon', 'Yovel, Yossi']",,,,
,PMC,Conformational dynamics of the frameshift stimulatory structure in HIV-1,http://dx.doi.org/10.1261/rna.061655.117,PMC5558907,,,"Programmed ribosomal frameshifting (PRF) in HIV-1 is thought to be stimulated by a hairpin in the mRNA, although a pseudoknot-like triplex has also been proposed. Because the conformational dynamics of the stimulatory structure under tension applied by the ribosomal helicase during translation may play an important role in PRF, we used optical tweezers to apply tension to the HIV stimulatory structure and monitor its unfolding and refolding dynamics. The folding and unfolding kinetics and energy landscape of the hairpin were measured by ramping the force on the hairpin up and down, providing a detailed biophysical characterization. Unexpectedly, whereas unfolding reflected the simple two-state behavior typical of many hairpins, refolding was more complex, displaying significant heterogeneity. Evidence was found for multiple refolding pathways as well as previously unsuspected, partially folded intermediates. Measuring a variant mRNA containing only the sequence required to form the proposed triplex, it behaved largely in the same way. Nonetheless, very rarely, high-force unfolding events characteristic of pseudoknot-like structures were observed. The rare occurrence of the triplex suggests that the hairpin is the functional stimulatory structure. The unusual heterogeneity of the hairpin dynamics under tension suggests a possible functional role in PRF similar to the dynamics of other stimulatory structures.",,"['Ritchie, Dustin B.', 'Cappellano, Tonia R.', 'Tittle, Collin', 'Rezajooei, Negar', 'Rouleau, Logan', 'Sikkema, William K.A.', 'Woodside, Michael T.']",,,,
,PMC,Sensitivity to BST-2 restriction correlates with Orthobunyavirus host range,http://dx.doi.org/10.1016/j.virol.2017.06.017,PMC5526858,28628828,CC BY,"Orthobunyaviruses include several recently emerging viruses of significant medical and veterinary importance. There is currently very limited understanding on what determines the host species range of these pathogens. In this study we discovered that BST-2/tetherin restricts orthobunyavirus replication in a host-specific manner. We show that viruses with human tropism (Oropouche virus and La Crosse virus) are restricted by sheep BST-2 but not by the human orthologue, while viruses with ruminant tropism (Schmallenberg virus and others) are restricted by human BST-2 but not by the sheep orthologue. We also show that BST-2 blocks orthobunyaviruses replication by reducing the amount of envelope glycoprotein into viral particles egressing from infected cells. This is the first study identifying a restriction factor that correlates with species susceptibility to orthobunyavirus infection. This work provides insight to help us dissect the adaptive changes that bunyaviruses require to cross the species barrier and emerge into new species.",2017 Sep,"['Varela, Mariana', 'Piras, Ilaria M.', 'Mullan, Catrina', 'Shi, Xiaohong', 'Tilston-Lunel, Natasha L.', 'Pinto, Rute Maria', 'Taggart, Aislynn', 'Welch, Stephen R.', 'Neil, Stuart J.D.', 'Kreher, Felix', 'Elliott, Richard M.', 'Palmarini, Massimo']",Virology,,,
,PMC,Assessment of half-mask elastomeric respirator and powered airpurifying respirator reprocessing for an influenza pandemic,http://dx.doi.org/10.1016/j.ajic.2017.06.034,PMC6193495,,,"BACKGROUND: Health care facilities are considering the use of reusable respiratory protective devices (RPDs) to mitigate a potential N95 filtering facepiece respirator shortage caused by an influenza pandemic. US regulators are also considering stockpiling reusable RPDs for pandemic preparedness, but limited data exist on the effectiveness of cleaning and disinfection of these devices. This study defines reprocessing protocols and evaluates their effectiveness against a pandemic influenza strain in a laboratory setting. METHODS: Five half-mask elastomeric respirator models and 3 powered air-purifying respirator models were contaminated with influenza virus and artificial skin oil on multiple surfaces. RPDs were then manually treated with 1 of 2 methods: cleaned or cleaned and disinfected. Presence of viable influenza was determined via swab sampling and a median tissue culture infectious dose assay. RESULTS: Across 41 RPD surfaces, a mean log reduction in viable influenza of 4.54 ±0.97 log(10) median tissue culture infectious dose was achieved for all treated surfaces, which included both cleaned and cleaned and disinfected surfaces. CONCLUSIONS: The methods defined as part of this study are effective for eliminating viable influenza in the presence of artificial skin oil on most of the RPD surfaces tested. Material type and RPD design should be considered when implementing RPD reprocessing protocols.",,"['Lawrence, Caryn', 'Harnish, Delbert A.', 'Sandoval-Powers, Megan', 'Mills, Devin', 'Bergman, Michael', 'Heimbuch, Brian K.']",,,,
,PMC,Novel Alphacoronaviruses and Paramyxoviruses Cocirculate with Type 1 and Severe Acute Respiratory System (SARS)-Related Betacoronaviruses in Synanthropic Bats of Luxembourg,http://dx.doi.org/10.1128/AEM.01326-17,PMC5583486,,,"Several infectious disease outbreaks with high mortality in humans have been attributed to viruses that are thought to have evolved from bat viruses. In this study from Luxembourg, the genetic diversity and epidemiology of paramyxoviruses and coronaviruses shed by the bat species Rhinolophus ferrumequinum and Myotis emarginatus were evaluated. Feces collection (n = 624) was performed longitudinally in a mixed-species colony in 2015 and 2016. In addition, feces (n = 254) were collected cross-sectionally from six Myotis emarginatus colonies in 2016. By use of degenerate primers in a nested format, overall prevalences of 1.1% (10/878) and 4.9% (43/878) were determined for paramyxoviruses and coronaviruses. Sequences of the partial RNA-dependent RNA polymerase and spike glycoprotein genes of coronaviruses, as well as sequences of the partial L gene of paramyxoviruses, were obtained. Novel paramyxovirus and Alphacoronavirus strains were identified in different Myotis emarginatus colonies, and severe acute respiratory syndrome (SARS)-related Betacoronavirus strains were shed by Rhinolophus ferrumequinum. Logistic regression revealed that the level of Alphacoronavirus shedding was highest in July (odds ratio, 2.8; P < 0.01), probably due to periparturient stress. Phylogenetic analyses point to close virus-host coevolution, and the high genetic similarity of the study strains suggests that the Myotis emarginatus colonies in Luxembourg are socially connected. Most interestingly, we show that bats also host Betacoronavirus 1 strains. The high similarity of the spike gene sequences of these viruses with mammalian Betacoronavirus 1 strains may be of concern. Both the SARS-related and Betacoronavirus 1 strains detected in bats in Luxembourg may cross the species barrier after a host adaptation process. IMPORTANCE Bats are a natural reservoir of a number of zoonotic pathogens. Several severe outbreaks in humans (e.g., a Nipah virus outbreak in Malaysia in 1998, and the almost global spread of severe acute respiratory syndrome in 2003) have been caused by bat-borne viruses that were transmitted to humans mostly after virus adaptation (e.g., in intermediate animal hosts). Despite the indigenousness of bat species that host viruses with suspected zoonotic potential and despite the zoonotic transmission of European bat 1 lyssavirus in Luxembourg, knowledge about the diversity and epidemiology of bat viruses remains limited in this country. Moreover, in contrast to other European countries, bat viruses are currently not included in the national surveillance activities of this land-locked country. We suggest that this gap in disease surveillance should be addressed, since we show here that synanthropic bats host viruses that may be able to cross the species barrier.",,"['Pauly, Maude', 'Pir, Jacques B.', 'Loesch, Catherine', 'Sausy, Aurélie', 'Snoeck, Chantal J.', 'Hübschen, Judith M.', 'Muller, Claude P.']",,,,
,PMC,Health as a “global public good”: creating a market for pandemic risk,http://dx.doi.org/10.1136/bmj.j3397,PMC5594412,28860109,CC BY,In the final article of the series Felix Stein and Devi Sridhar examine how the World Bank is trying to provide finance to improve preparedness for global pandemics,2017 Aug 31,"['Stein, Felix', 'Sridhar, Devi']",BMJ,,,
,PMC,The Role of BAFF System Molecules in Host Response to Pathogens,http://dx.doi.org/10.1128/CMR.00046-17,PMC5608883,,,"The two ligands B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) and the three receptors BAFF receptor (BAFF-R), transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI), and B cell maturation antigen (BCMA) are members of the “BAFF system molecules.” BAFF system molecules are primarily involved in B cell homeostasis. The relevance of BAFF system molecules in host responses to microbial assaults has been investigated in clinical studies and in mice deficient for each of these molecules. Many microbial products modulate the expression of these molecules. Data from clinical studies suggest a correlation between increased expression levels of BAFF system molecules and elevated B cell responses. Depending on the pathogen, heightened B cell responses may strengthen the host response or promote susceptibility. Whereas pathogen-mediated increases in the expression levels of the ligands and/or the receptors appear to promote microbial clearance, certain pathogens have evolved to ablate B cell responses by suppressing the expression of TACI and/or BAFF-R on B cells. Other than its well-established role in B cell responses, the TACI-mediated activation of macrophages is also implicated in resistance to intracellular pathogens. An improved understanding of the role that BAFF system molecules play in infection may assist in devising novel strategies for vaccine development.",,"['Sakai, Jiro', 'Akkoyunlu, Mustafa']",,,,
,PMC,CCL28 chemokine: An anchoring point bridging innate and adaptive immunity,http://dx.doi.org/10.1016/j.intimp.2017.08.012,PMC5755716,,,"Chemokines are an extensive family of small proteins which, in conjunction with their receptors, guide the chemotactic activity of various immune cells throughout the body. CCL28, β- or CC chemokine, is involved in the host immunity at various epithelial and mucosal linings. The unique roles of CCL28 in several facets of immune responses have attracted considerable attention and may represent a promising approach to combat various infections. CCL28 displays a broad spectrum of antimicrobial activity against gram-negative and gram-positive bacteria, as well as fungi. Here, we will summarize various research findings regarding the antimicrobial activity of CCL28 and the relevant mechanisms behind it. We will explore how the structure of CCL28 is involved with this activity and how this function may have evolved. CCL28 displays strong homing capabilities for B and T cells at several mucosal and epithelial sites, and orchestrates the trafficking and functioning of lymphocytes. The chemotactic and immunomodulatory features of CCL28 through the interactions with its chemokine receptors, CCR10 and CCR3, will also be discussed in detail. Thus, in this review, we emphasize the dual properties of CCL28 and suggest its role as an anchoring point bridging the innate and adaptive immunity.",,"['Mohan, Teena', 'Deng, Lei', 'Wang, Bao-Zhong']",,,,
,PMC,"Heated, humidified air for the common cold",http://dx.doi.org/10.1002/14651858.CD001728.pub6,PMC6483632,,,"BACKGROUND: Heated, humidified air has long been used by people with the common cold. The theoretical basis is that steam may help congested mucus drain better and that heat may destroy the cold virus as it does in vitro. This is an update of a review last published in 2013. OBJECTIVES: To assess the effects of inhaling heated water vapour (steam) in the treatment of the common cold by comparing symptoms, viral shedding, and nasal resistance. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (to February 2017), MEDLINE (1966 to 24 February 2017), Embase (1990 to 24 February 2017), and Current Contents (1998 to 24 February 2017). We also searched World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (8 March 2017) and ClinicalTrials.gov (8 March 2017) as well as reference lists of included studies. SELECTION CRITERIA: Randomised controlled trials using heated water vapour in participants with the common cold or experimentally induced common cold were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Three review authors independently screened titles and abstracts for inclusion of potential studies identified from the search. We recorded the selection process in sufficient detail to complete a PRISMA flow diagram. We used a data collection form for study characteristics and outcome data that was developed and used for previous versions of this review. Two review authors independently extracted data, and a third review author resolved any disagreements. We used Review Manager 5 software to analyse data. MAIN RESULTS: We included six trials from five publications involving a total of 387 participants. We included no new studies in this 2017 update. The 'Risk of bias' assessment suggested an unclear risk of bias in the domain of randomisation and a low risk of bias in performance, detection, attrition, and reporting. It was uncertain whether heated, humidified air provides symptomatic relief for the common cold, as the fixed‐effect analysis showed evidence of an effect (odds ratio (OR) 0.30, 95% confidence interval (CI) 0.16 to 0.56; 2 studies, 149 participants), but the random‐effects analysis showed no significant difference in the results (OR 0.22, 95% CI 0.03 to 1.95). There is an argument for using either form of analysis. No studies demonstrated an exacerbation of clinical symptom scores. One study conducted in the USA demonstrated worsened nasal resistance, but an earlier Israeli study showed improvement. One study examined viral shedding in nasal washings, finding no significant difference between treatment and placebo groups (OR 0.47, 95% CI 0.04 to 5.19). As judged by the subjective response to therapy (i.e. therapy did not help), the number of participants reporting resolution of symptoms was not significantly higher in the heated humidified group (OR 0.58, 95% CI 0.28 to 1.18; 2 studies, 124 participants). There was significant heterogeneity in the effects of heated, humidified air on different outcomes, therefore we graded the quality of the evidence as low. Some studies reported minor adverse events (including discomfort or irritation of the nose). AUTHORS' CONCLUSIONS: The current evidence does not show any benefits or harms from the use of heated, humidified air delivered via the RhinoTherm device for the treatment of the common cold. There is a need for more double‐blind, randomised trials that include standardised treatment modalities.",,"['Singh, Meenu', 'Singh, Manvi', 'Jaiswal, Nishant', 'Chauhan, Anil']",,,,
,PMC,PNAS Plus Significance Statements,http://dx.doi.org/10.1073/pnas.ss11435,PMC5584470,,,,,,,,,
,PMC,"Zika, Chikungunya, and Other Emerging Vector-Borne Viral Diseases",http://dx.doi.org/10.1146/annurev-med-050715-105122,PMC6343128,,,"Arthropod-borne viruses (arboviruses) have a long history of emerging to infect humans, but during recent decades, they have been spreading more widely and affecting larger populations. This is due to several factors, including increased air travel and uncontrolled mosquito vector populations. Emergence can involve simple spillover from enzootic (wildlife) cycles, as in the case of West Nile virus accompanying geographic expansion into the Americas; secondary amplification in domesticated animals, as seen with Japanese encephalitis, Venezuelan equine encephalitis, and Rift Valley fever viruses; and urbanization, in which humans become the amplification hosts and peridomestic mosquitoes, mainly Aedes aegypti, mediate human-to-human transmission. Dengue, yellow fever, chikungunya, and Zika viruses have undergone such urban emergence. We focus mainly on the latter two, which are recent arrivals in the Western Hemisphere. We also discuss a few other viruses with the potential to emerge through all of these mechanisms.",,"['Weaver, Scott C.', 'Charlier, Caroline', 'Vasilakis, Nikos', 'Lecuit, Marc']",,,,
,PMC,Identification of trans Protein QTL for Secreted Airway Mucins in Mice and a Causal Role for Bpifb1,http://dx.doi.org/10.1534/genetics.117.300211,PMC5629340,,,"Mucus hyper-secretion is a hallmark feature of asthma and other muco-obstructive airway diseases. The mucin proteins MUC5AC and MUC5B are the major glycoprotein components of mucus and have critical roles in airway defense. Despite the biomedical importance of these two proteins, the loci that regulate them in the context of natural genetic variation have not been studied. To identify genes that underlie variation in airway mucin levels, we performed genetic analyses in founder strains and incipient lines of the Collaborative Cross (CC) in a house dust mite mouse model of asthma. CC founder strains exhibited significant differences in MUC5AC and MUC5B, providing evidence of heritability. Analysis of gene and protein expression of Muc5ac and Muc5b in incipient CC lines (n = 154) suggested that post-transcriptional events were important regulators of mucin protein content in the airways. Quantitative trait locus (QTL) mapping identified distinct, trans protein QTL for MUC5AC (chromosome 13) and MUC5B (chromosome 2). These two QTL explained 18 and 20% of phenotypic variance, respectively. Examination of the MUC5B QTL allele effects and subsequent phylogenetic analysis allowed us to narrow the MUC5B QTL and identify Bpifb1 as a candidate gene. Bpifb1 mRNA and protein expression were upregulated in parallel to MUC5B after allergen challenge, and Bpifb1 knockout mice exhibited higher MUC5B expression. Thus, BPIFB1 is a novel regulator of MUC5B.",,"['Donoghue, Lauren J.', 'Livraghi-Butrico, Alessandra', 'McFadden, Kathryn M.', 'Thomas, Joseph M.', 'Chen, Gang', 'Grubb, Barbara R.', 'O’Neal, Wanda K.', 'Boucher, Richard C.', 'Kelada, Samir N. P.']",,,,
,PMC,Potent Inhibition of HIV-1 Replication in Resting CD4 T Cells by Resveratrol and Pterostilbene,http://dx.doi.org/10.1128/AAC.00408-17,PMC5571302,,,"HIV-1 infection of resting CD4 T cells plays a crucial and numerically dominant role during virus transmission at mucosal sites and during subsequent acute replication and T cell depletion. Resveratrol and pterostilbene are plant stilbenoids associated with several health-promoting benefits. Resveratrol has been shown to inhibit the replication of several viruses, including herpes simplex viruses 1 and 2, papillomaviruses, severe acute respiratory syndrome virus, and influenza virus. Alone, resveratrol does not inhibit HIV-1 infection of activated T cells, but it does synergize with nucleoside reverse transcriptase inhibitors in these cells to inhibit reverse transcription. Here, we demonstrate that resveratrol and pterostilbene completely block HIV-1 infection at a low micromolar dose in resting CD4 T cells, primarily at the reverse transcription step. The anti-HIV effect was fully reversed by exogenous deoxynucleosides and Vpx, an HIV-1 and simian immunodeficiency virus protein that increases deoxynucleoside triphosphate (dNTP) levels. These findings are consistent with the reported ability of resveratrol to inhibit ribonucleotide reductase and to lower dNTP levels in cells. This study supports the potential use of resveratrol, pterostilbene, or related compounds as adjuvants in anti-HIV preexposure prophylaxis (PrEP) formulations.",,"['Chan, Chi N.', 'Trinité, Benjamin', 'Levy, David N.']",,,,
,PMC,Partially Uncleaved Alphavirus Replicase Forms Spherule Structures in the Presence and Absence of RNA Template,http://dx.doi.org/10.1128/JVI.00787-17,PMC5571266,,,"Alphaviruses are positive-strand RNA viruses expressing their replicase as a polyprotein, P1234, which is cleaved to four final products, nonstructural proteins nsP1 to nsP4. The replicase proteins together with viral RNA and host factors form membrane invaginations termed spherules, which act as the replication complexes producing progeny RNAs. We have previously shown that the wild-type alphavirus replicase requires a functional RNA template and active polymerase to generate spherule structures. However, we now find that specific partially processed forms of the replicase proteins alone can give rise to membrane invaginations in the absence of RNA or replication. The minimal requirement for spherule formation was the expression of properly cleaved nsP4, together with either uncleaved P123 or with the combination of nsP1 and uncleaved P23. These inactive spherules were morphologically less regular than replication-induced spherules. In the presence of template, nsP1 plus uncleaved P23 plus nsP4 could efficiently assemble active replication spherules producing both negative-sense and positive-sense RNA strands. P23 alone did not have membrane affinity, but could be recruited to membrane sites in the presence of nsP1 and nsP4. These results define the set of viral components required for alphavirus replication complex assembly and suggest the possibility that it could be reconstituted from separately expressed nonstructural proteins. IMPORTANCE All positive-strand RNA viruses extensively modify host cell membranes to serve as efficient platforms for viral RNA replication. Alphaviruses and several other groups induce protective membrane invaginations (spherules) as their genome factories. Most positive-strand viruses produce their replicase as a polyprotein precursor, which is further processed through precise and regulated cleavages. We show here that specific cleavage intermediates of the alphavirus replicase can give rise to spherule structures in the absence of viral RNA. In the presence of template RNA, the same intermediates yield active replication complexes. Thus, partially cleaved replicase proteins play key roles that connect replication complex assembly, membrane deformation, and the different stages of RNA synthesis.",,"['Hellström, Kirsi', 'Kallio, Katri', 'Utt, Age', 'Quirin, Tania', 'Jokitalo, Eija', 'Merits, Andres', 'Ahola, Tero']",,,,
,PMC,Entry and Release of Hepatitis C Virus in Polarized Human Hepatocytes,http://dx.doi.org/10.1128/JVI.00478-17,PMC5571255,,,"Hepatitis C virus (HCV) primarily infects hepatocytes, which are highly polarized cells. The relevance of cell polarity in the HCV life cycle has been addressed only in distantly related models and remains poorly understood. Although polarized epithelial cells have a rather simple morphology with a basolateral and an apical domain, hepatocytes exhibit complex polarization structures. However, it has been reported that some selected polarized HepG2 cell clones can exhibit a honeycomb pattern of distribution of the tight-junction proteins typical of columnar polarized epithelia, which can be used as a simple model to study the role of cell polarization in viral infection of hepatocytes. To obtain similar clones, HepG2 cells expressing CD81 (HepG2-CD81) were used, and clones were isolated by limiting dilutions. Two clones exhibiting a simple columnar polarization capacity when grown on a semipermeable support were isolated and characterized. To test the polarity of HCV entry and release, our polarized HepG2-CD81 clones were infected with cell culture-derived HCV. Our data indicate that HCV binds equally to both sides of the cells, but productive infection occurs mainly when the virus is added at the basolateral domain. Furthermore, we also observed that HCV virions are released from the basolateral domain of the cells. Finally, when polarized cells were treated with oleic acid and U0126, a MEK inhibitor, to promote lipoprotein secretion, a higher proportion of infectious viral particles of lower density were secreted. This cell culture system provides an excellent model to investigate the influence of cell polarization on the HCV life cycle. IMPORTANCE Hepatitis C is a major health burden, with approximately 170 million persons infected worldwide. Hepatitis C virus (HCV) primarily infects hepatocytes, which are highly polarized cells with a complex organization. The relevance of cell polarity in the HCV life cycle has been addressed in distantly related models and remains unclear. Hepatocyte organization is complex, with multiple apical and basolateral surfaces. A simple culture model of HepG2 cells expressing CD81 that are able to polarize with unique apical and basolateral domains was developed to study HCV infection. With this model, we demonstrated that HCV enters and exits hepatocytes by the basolateral domain. Furthermore, lower-density viral particles were produced under conditions that promote lipoprotein secretion. This cell culture system provides a useful model to study the influence of cell polarization on HCV infection.",,"['Belouzard, Sandrine', 'Danneels, Adeline', 'Fénéant, Lucie', 'Séron, Karin', 'Rouillé, Yves', 'Dubuisson, Jean']",,,,
,PMC,IFITM3 requires an amphipathic helix for antiviral activity,http://dx.doi.org/10.15252/embr.201744100,PMC5623871,,,"Interferon‐induced transmembrane protein 3 (IFITM3) is a cellular factor that blocks virus fusion with cell membranes. IFITM3 has been suggested to alter membrane curvature and fluidity, though its exact mechanism of action is unclear. Using a bioinformatic approach, we predict IFITM3 secondary structures and identify a highly conserved, short amphipathic helix within a hydrophobic region of IFITM3 previously thought to be a transmembrane domain. Consistent with the known ability of amphipathic helices to alter membrane properties, we show that this helix and its amphipathicity are required for the IFITM3‐dependent inhibition of influenza virus, Zika virus, vesicular stomatitis virus, Ebola virus, and human immunodeficiency virus infections. The homologous amphipathic helix within IFITM1 is also required for the inhibition of infection, indicating that IFITM proteins possess a conserved mechanism of antiviral action. We further demonstrate that the amphipathic helix of IFITM3 is required to block influenza virus hemagglutinin‐mediated membrane fusion. Overall, our results provide evidence that IFITM proteins utilize an amphipathic helix for inhibiting virus fusion.",,"['Chesarino, Nicholas M', 'Compton, Alex A', 'McMichael, Temet M', 'Kenney, Adam D', 'Zhang, Lizhi', 'Soewarna, Victoria', 'Davis, Matthew', 'Schwartz, Olivier', 'Yount, Jacob S']",,,,
,PMC,The Invisible Army,http://dx.doi.org/10.1128/JCM.00658-17,PMC5648695,,,"The “invisible army” of clinical microbiologists is facing major changes and challenges. The rate of change in both the science and technology is accelerating with no end in sight, putting pressure on our army to learn and adapt as never before. Health care funding in the United States is undergoing dramatic change which will require a new set of assumptions about how clinical microbiology is practiced here. A major challenge facing the discipline is the replacement of a generation of clinical microbiologists. In my opinion, it is incumbent on us in the invisible army to continue to work with the American Society for Microbiology (ASM) in meeting the future challenges faced by our discipline. In this commentary, I will first discuss some recent history of clinical microbiology within ASM and then some current challenges we face.",,"Gilligan, Peter H.",,,,
,PMC,Diseases and Molecular Diagnostics: A Step Closer to Precision Medicine,http://dx.doi.org/10.1007/s12291-017-0688-8,PMC5634985,,,"The current advent of molecular technologies together with a multidisciplinary interplay of several fields led to the development of genomics, which concentrates on the detection of pathogenic events at the genome level. The structural and functional genomics approaches have now pinpointed the technical challenge in the exploration of disease-related genes and the recognition of their structural alterations or elucidation of gene function. Various promising technologies and diagnostic applications of structural genomics are currently preparing a large database of disease-genes, genetic alterations etc., by mutation scanning and DNA chip technology. Further the functional genomics also exploring the expression genetics (hybridization-, PCR- and sequence-based technologies), two-hybrid technology, next generation sequencing with Bioinformatics and computational biology. Advances in microarray “chip” technology as microarrays have allowed the parallel analysis of gene expression patterns of thousands of genes simultaneously. Sequence information collected from the genomes of many individuals is leading to the rapid discovery of single nucleotide polymorphisms or SNPs. Further advances of genetic engineering have also revolutionized immunoassay biotechnology via engineering of antibody-encoding genes and the phage display technology. The Biotechnology plays an important role in the development of diagnostic assays in response to an outbreak or critical disease response need. However, there is also need to pinpoint various obstacles and issues related to the commercialization and widespread dispersal of genetic knowledge derived from the exploitation of the biotechnology industry and the development and marketing of diagnostic services. Implementation of genetic criteria for patient selection and individual assessment of the risks and benefits of treatment emerges as a major challenge to the pharmaceutical industry. Thus this field is revolutionizing current era and further it may open new vistas in the field of disease management.",,"['Dwivedi, Shailendra', 'Purohit, Purvi', 'Misra, Radhieka', 'Pareek, Puneet', 'Goel, Apul', 'Khattri, Sanjay', 'Pant, Kamlesh Kumar', 'Misra, Sanjeev', 'Sharma, Praveen']",,,,
,PMC,Structures of phlebovirus glycoprotein Gn and identification of a neutralizing antibody epitope,http://dx.doi.org/10.1073/pnas.1705176114,PMC5594662,,,"Severe fever with thrombocytopenia syndrome virus (SFTSV) and Rift Valley fever virus (RVFV) are two arthropod-borne phleboviruses in the Bunyaviridae family, which cause severe illness in humans and animals. Glycoprotein N (Gn) is one of the envelope proteins on the virus surface and is a major antigenic component. Despite its importance for virus entry and fusion, the molecular features of the phleboviruse Gn were unknown. Here, we present the crystal structures of the Gn head domain from both SFTSV and RVFV, which display a similar compact triangular shape overall, while the three subdomains (domains I, II, and III) making up the Gn head display different arrangements. Ten cysteines in the Gn stem region are conserved among phleboviruses, four of which are responsible for Gn dimerization, as revealed in this study, and they are highly conserved for all members in Bunyaviridae. Therefore, we propose an anchoring mode on the viral surface. The complex structure of the SFTSV Gn head and human neutralizing antibody MAb 4–5 reveals that helices α6 in subdomain III is the key component for neutralization. Importantly, the structure indicates that domain III is an ideal region recognized by specific neutralizing antibodies, while domain II is probably recognized by broadly neutralizing antibodies. Collectively, Gn is a desirable vaccine target, and our data provide a molecular basis for the rational design of vaccines against the diseases caused by phleboviruses and a model for bunyavirus Gn embedding on the viral surface.",,"['Wu, Yan', 'Zhu, Yaohua', 'Gao, Feng', 'Jiao, Yongjun', 'Oladejo, Babayemi O.', 'Chai, Yan', 'Bi, Yuhai', 'Lu, Shan', 'Dong, Mengqiu', 'Zhang, Chang', 'Huang, Guangmei', 'Wong, Gary', 'Li, Na', 'Zhang, Yanfang', 'Li, Yan', 'Feng, Wen-hai', 'Shi, Yi', 'Liang, Mifang', 'Zhang, Rongguang', 'Qi, Jianxun', 'Gao, George F.']",,,,
,PMC,DETECTION OF RESPIRATORY SYNCYTIAL VIRUS (RSV) AT BIRTH IN A NEWBORN WITH RESPIRATORY DISTRESS,http://dx.doi.org/10.1002/ppul.23775,PMC5657560,,,"Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children. From the nasopharyngeal or conjunctival mucosa of infected individuals, RSV spreads to the lower respiratory tract causing acute bronchiolitis and pneumonia after an incubation period of 4 to 6 days. In addition to its well-documented tropism for the airway epithelium, it has been shown previously that RSV can also spread hematogenously and efficiently infect extrapulmonary tissues of human hosts. Furthermore, it has been shown in animal models that RSV can spread transplacentally from the respiratory tract of a pregnant mother to the lungs of the fetus. This report describes a documented case of neonatal RSV infection strongly suggestive of prenatal transmission of this infection in humans from an infected mother to her offspring.",,"['Manti, Sara', 'Cuppari, Caterina', 'Lanzafame, Angela', 'Salpietro, Carmelo', 'Betta, Pasqua', 'Leonardi, Salvatore', 'Perez, Miriam K.', 'Piedimonte, Giovanni']",,,,
,PMC,Association of Dynamic Changes in the CD4 T-Cell Transcriptome With Disease Severity During Primary Respiratory Syncytial Virus Infection in Young Infants,http://dx.doi.org/10.1093/infdis/jix400,PMC5853440,,,"BACKGROUND: Nearly all children are infected with respiratory syncytial virus (RSV) within the first 2 years of life, with a minority developing severe disease (1%–3% hospitalized). We hypothesized that an assessment of the adaptive immune system, using CD4(+) T-lymphocyte transcriptomics, would identify gene expression correlates of disease severity. METHODS: Infants infected with RSV representing extremes of clinical severity were studied. Mild illness (n = 23) was defined as a respiratory rate (RR) < 55 and room air oxygen saturation (SaO(2)) ≥ 97%, and severe illness (n = 23) was defined as RR ≥ 65 and SaO2 ≤ 92%. RNA from fresh, sort-purified CD4(+) T cells was assessed by RNA sequencing. RESULTS: Gestational age, age at illness onset, exposure to environmental tobacco smoke, bacterial colonization, and breastfeeding were associated (adjusted P < .05) with disease severity. RNA sequencing analysis reliably measured approximately 60% of the genome. Severity of RSV illness had the greatest effect size upon CD4 T-cell gene expression. Pathway analysis identified correlates of severity, including JAK/STAT, prolactin, and interleukin 9 signaling. We also identified genes and pathways associated with timing of symptoms and RSV group (A/B). CONCLUSIONS: These data suggest fundamental changes in adaptive immune cell phenotypes may be associated with RSV clinical severity.",,"['Mariani, Thomas J', 'Qiu, Xing', 'Chu, ChinYi', 'Wang, Lu', 'Thakar, Juilee', 'Holden-Wiltse, Jeanne', 'Corbett, Anthony', 'Topham, David J', 'Falsey, Ann R', 'Caserta, Mary T', 'Walsh, Edward E']",,,,
,PMC,Neural precursor cells derived from induced pluripotent stem cells exhibit reduced susceptibility to infection with a neurotropic coronavirus,http://dx.doi.org/10.1016/j.virol.2017.08.003,PMC5623645,,,"The present study examines the susceptibility of mouse induced pluripotent stem cell-derived neural precursor cells (iPSC-NPCs) to infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV). Similar to NPCs derived from striatum of day 1 postnatal GFP-transgenic mice (GFP-NPCs), iPSC-derived NPCs (iPSC-NPCs) are able to differentiate into terminal neural cell types and express MHC class I and II in response to IFN-γ treatment. However, in contrast to postnatally-derived NPCs, iPSC-NPCs express low levels of carcinoembryonic antigen-cell adhesion molecule 1a (CEACAM1a), the surface receptor for JHMV, and are less susceptible to infection and virus-induced cytopathic effects. The relevance of this in terms of therapeutic application of NPCs resistant to viral infection is discussed.",,"['Mangale, Vrushali', 'Marro, Brett S.', 'Plaisted, Warren C.', 'Walsh, Craig M.', 'Lane, Thomas E.']",,,,
,PMC,Reduced dynamic range of antiviral innate immune responses in aging,http://dx.doi.org/10.1016/j.exger.2017.08.019,PMC5815956,,,"The worldwide population aged ≥65 years is increasing and the average life span is expected to increase another 10 years by 2050. This extended lifespan is associated with a progressive decline in immune function and a paradoxical state of low-grade, chronic inflammation that may contribute to susceptibility to viral infection, and reduced responses to vaccination. Here we review the effects of aging on innate immune responses to viral pathogens including elements of recognition, signaling, and production of inflammatory mediators. We specifically focus on age-related changes in key pattern recognition receptor signaling pathways, converging on altered cytokine responses with age, including a notable impairment of antiviral interferon responses. We highlight an emergent change in innate immunity that arises during aging –the dampening of the dynamic range of responses to multiple sources of stimulation – which may underlie reduced efficiency of immune responses in aging.",,"['Molony, Ryan D.', 'Malawista, Anna', 'Montgomery, Ruth R.']",,,,
,PMC,Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen,http://dx.doi.org/10.1073/pnas.1707304114,PMC5584442,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV. We also determined high-resolution structures of the trimeric MERS-CoV S ectodomain in complex with G4, a stem-directed neutralizing antibody. The structures reveal that G4 recognizes a glycosylated loop that is variable among coronaviruses and they define four conformational states of the trimer wherein each receptor-binding domain is either tightly packed at the membrane-distal apex or rotated into a receptor-accessible conformation. Our studies suggest a potential mechanism for fusion initiation through sequential receptor-binding events and provide a foundation for the structure-based design of coronavirus vaccines.",,"['Pallesen, Jesper', 'Wang, Nianshuang', 'Corbett, Kizzmekia S.', 'Wrapp, Daniel', 'Kirchdoerfer, Robert N.', 'Turner, Hannah L.', 'Cottrell, Christopher A.', 'Becker, Michelle M.', 'Wang, Lingshu', 'Shi, Wei', 'Kong, Wing-Pui', 'Andres, Erica L.', 'Kettenbach, Arminja N.', 'Denison, Mark R.', 'Chappell, James D.', 'Graham, Barney S.', 'Ward, Andrew B.', 'McLellan, Jason S.']",,,,
,PMC,A Neuroprimer: Principles of CNS Immunity,http://dx.doi.org/10.1016/j.spen.2017.08.004,PMC5687309,,,"Despite longstanding perceptions, robust innate and adaptive immune responses occur within the central nervous system (CNS) in response to infection and tissue damage. Although necessary to control infection, immune responses can lead to severe CNS pathology in the context of both viral infection and autoimmunity. Research into how the central nervous and immune systems communicate has accelerated over the past 20 years leading to a better understanding of pathways controlling immune activation and neuroinflammation that have guided the approval of new disease-modifying therapies to treat CNS immunopathology, particularly the inflammatory demyelinating disease multiple sclerosis. This article provides an introduction into the basic principles underlying immune responses within the CNS that developed from experimental animal models of both neurotropic virus infection and autoimmune T cell mediated CNS demyelination.",,"Owens, Gregory P.",,,,
,PMC,Conserved Vδ1 Binding Geometry in a Setting of Locus-Disparate pHLA Recognition by δ/αβ T Cell Receptors (TCRs): Insight into Recognition of HIV Peptides by TCRs,http://dx.doi.org/10.1128/JVI.00725-17,PMC5553175,,,"Given the limited set of T cell receptor (TCR) V genes that are used to create TCRs that are reactive to different ligands, such as major histocompatibility complex (MHC) class I, MHC class II, and MHC-like proteins (for example, MIC molecules and CD1 molecules), the Vδ1 segment can be rearranged with Dδ-Jδ-Cδ or Jα-Cα segments to form classical γδTCRs or uncommon αβTCRs using a Vδ1 segment (δ/αβTCR). Here we have determined two complex structures of the δ/αβTCRs (S19-2 and TU55) bound to different locus-disparate MHC class I molecules with HIV peptides (HLA-A*2402-Nef138-10 and HLA-B*3501-Pol448-9). The overall binding modes resemble those of classical αβTCRs but display a strong tilt binding geometry of the Vδ1 domain toward the HLA α1 helix, due to a conserved extensive interaction between the CDR1δ loop and the N-terminal region of the α1 helix (mainly in position 62). The aromatic amino acids of the CDR1δ loop exploit different conformations (“aromatic ladder” or “aromatic hairpin”) to accommodate distinct MHC helical scaffolds. This tolerance helps to explain how a particular TCR V region can similarly dock onto multiple MHC molecules and thus may potentially explain the nature of TCR cross-reactivity. In addition, the length of the CDR3δ loop could affect the extent of tilt binding of the Vδ1 domain, and adaptively, the pairing Vβ domains adjust their mass centers to generate differential MHC contacts, hence probably ensuring TCR specificity for a certain peptide-MHC class I (pMHC-I). Our data have provided further structural insights into the TCR recognition of classical pMHC-I molecules, unifying cross-reactivity and specificity. IMPORTANCE The specificity of αβ T cell recognition is determined by the CDR loops of the αβTCR, and the general mode of binding of αβTCRs to pMHC has been established over the last decade. Due to the intrinsic genomic structure of the TCR α/δ chain locus, some Vδ segments can rearrange with the Cα segment, forming a hybrid VδCαVβCβ TCR, the δ/αβTCR. However, the basis for the molecular recognition of such TCRs of their ligands is elusive. Here an αβTCR using the Vδ1 segment, S19-2, was isolated from an HIV-infected patient in an HLA-A*24:02-restricted manner. We then solved the crystal structures of the S19-2 TCR and another δ/αβTCR, TU55, bound to their respective ligands, revealing a conserved Vδ1 binding feature. Further binding kinetics analysis revealed that the S19-2 and TU55 TCRs bind pHLA very tightly and in a long-lasting manner. Our results illustrate the mode of binding of a TCR using the Vδ1 segment to its ligand, virus-derived pHLA.",,"['Shi, Yi', 'Kawana-Tachikawa, Ai', 'Gao, Feng', 'Qi, Jianxun', 'Liu, Chuansheng', 'Gao, Jia', 'Cheng, Hao', 'Ueno, Takamasa', 'Iwamoto, Aikichi', 'Gao, George F.']",,,,
,PMC,Functional Evolution of Influenza Virus NS1 Protein in Currently Circulating Human 2009 Pandemic H1N1 Viruses,http://dx.doi.org/10.1128/JVI.00721-17,PMC5553169,,,"In 2009, a novel H1N1 influenza virus emerged in humans, causing a global pandemic. It was previously shown that the NS1 protein from this human 2009 pandemic H1N1 (pH1N1) virus was an effective interferon (IFN) antagonist but could not inhibit general host gene expression, unlike other NS1 proteins from seasonal human H1N1 and H3N2 viruses. Here we show that the NS1 protein from currently circulating pH1N1 viruses has evolved to encode 6 amino acid changes (E55K, L90I, I123V, E125D, K131E, and N205S) with respect to the original protein. Notably, these 6 residue changes restore the ability of pH1N1 NS1 to inhibit general host gene expression, mainly by their ability to restore binding to the cellular factor CPSF30. This is the first report describing the ability of the pH1N1 NS1 protein to naturally acquire mutations that restore this function. Importantly, a recombinant pH1N1 virus containing these 6 amino acid changes in the NS1 protein (pH1N1/NSs-6mut) inhibited host IFN and proinflammatory responses to a greater extent than that with the parental virus (pH1N1/NS1-wt), yet virus titers were not significantly increased in cell cultures or in mouse lungs, and the disease was partially attenuated. The pH1N1/NSs-6mut virus grew similarly to pH1N1/NSs-wt in mouse lungs, but infection with pH1N1/NSs-6mut induced lower levels of proinflammatory cytokines, likely due to a general inhibition of gene expression mediated by the mutated NS1 protein. This lower level of inflammation induced by the pH1N1/NSs-6mut virus likely accounts for the attenuated disease phenotype and may represent a host-virus adaptation affecting influenza virus pathogenesis. IMPORTANCE Seasonal influenza A viruses (IAVs) are among the most common causes of respiratory infections in humans. In addition, occasional pandemics are caused when IAVs circulating in other species emerge in the human population. In 2009, a swine-origin H1N1 IAV (pH1N1) was transmitted to humans, infecting people then and up to the present. It was previously shown that the NS1 protein from the 2009 pandemic H1N1 (pH1N1) virus is not able to inhibit general gene expression. However, currently circulating pH1N1 viruses have evolved to encode 6 amino acid changes (E55K, L90I, I123V, E125D, K131E, and N205S) that allow the NS1 protein of contemporary pH1N1 strains to inhibit host gene expression, which correlates with its ability to interact with CPSF30. Infection with a recombinant pH1N1 virus encoding these 6 amino acid changes (pH1N1/NSs-6mut) induced lower levels of proinflammatory cytokines, resulting in viral attenuation in vivo. This might represent an adaptation of pH1N1 virus to humans.",,"['Clark, Amelia M.', 'Nogales, Aitor', 'Martinez-Sobrido, Luis', 'Topham, David J.', 'DeDiego, Marta L.']",,,,
,PMC,Ifit2 Is a Restriction Factor in Rabies Virus Pathogenicity,http://dx.doi.org/10.1128/JVI.00889-17,PMC5553164,,,"Understanding the interactions between rabies virus (RABV) and individual host cell proteins is critical for the development of targeted therapies. Here we report that interferon-induced protein with tetratricopeptide repeats 2 (Ifit2), an interferon-stimulated gene (ISG) with possible RNA-binding capacity, is an important restriction factor for rabies virus. When Ifit2 was depleted, RABV grew more quickly in mouse neuroblastoma cells in vitro. This effect was replicated in vivo, where Ifit2 knockout mice displayed a dramatically more severe disease phenotype than wild-type mice after intranasal inoculation of RABV. This increase in pathogenicity correlated to an increase in RABV mRNA and live viral load in the brain, as well as to an accelerated spread to brain regions normally affected by this RABV model. These results suggest that Ifit2 exerts its antiviral effect mainly at the level of viral replication, as opposed to functioning as a mechanism that restricts viral entry/egress or transports RABV particles through axons. IMPORTANCE Rabies is a fatal zoonotic disease with a nearly 100% case fatality rate. Although there are effective vaccines for rabies, this disease still takes the lives of about 50,000 people each year. Victims tend to be children living in regions without comprehensive medical infrastructure who present to health care workers too late for postexposure prophylaxis. The protein discussed in our report, Ifit2, is found to be an important restriction factor for rabies virus, acting directly or indirectly against viral replication. A more nuanced understanding of this interaction may reveal a step of a pathway or site at which the system could be exploited for the development of a targeted therapy.",,"['Davis, Benjamin M.', 'Fensterl, Volker', 'Lawrence, Tessa M.', 'Hudacek, Andrew W.', 'Sen, Ganes C.', 'Schnell, Matthias J.']",,,,
,PMC,Discovery of a Highly Divergent Coronavirus in the Asian House Shrew from China Illuminates the Origin of the Alphacoronaviruses,http://dx.doi.org/10.1128/JVI.00764-17,PMC5553162,,,"Although shrews are one of the largest groups of mammals, little is known about their role in the evolution and transmission of viral pathogens, including coronaviruses (CoVs). We captured 266 Asian house shrews (Suncus murinus) in Jiangxi and Zhejiang Provinces, China, during 2013 to 2015. CoV RNA was detected in 24 Asian house shrews, with an overall prevalence of 9.02%. Complete viral genome sequences were successfully recovered from the RNA-positive samples. The newly discovered shrew CoV fell into four lineages reflecting their geographic origins, indicative of largely allopatric evolution. Notably, these viruses were most closely related to alphacoronaviruses but sufficiently divergent that they should be considered a novel member of the genus Alphacoronavirus, which we denote Wénchéng shrew virus (WESV). Phylogenetic analysis revealed that WESV was a highly divergent member of the alphacoronaviruses and, more dramatically, that the S gene of WESV fell in a cluster that was genetically distinct from that of known coronaviruses. The divergent position of WESV suggests that coronaviruses have a long association with Asian house shrews. In addition, the genome of WESV contains a distinct NS7 gene that exhibits no sequence similarity to genes of any known viruses. Together, these data suggest that shrews are natural reservoirs for coronaviruses and may have played an important and long-term role in CoV evolution. IMPORTANCE The subfamily Coronavirinae contains several notorious human and animal pathogens, including severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus, and porcine epidemic diarrhea virus. Because of their genetic diversity and phylogenetic relationships, it has been proposed that the alphacoronaviruses likely have their ultimate ancestry in the viruses residing in bats. Here, we describe a novel alphacoronavirus (Wénchéng shrew virus [WESV]) that was sampled from Asian house shrews in China. Notably, WESV is a highly divergent member of the alphacoronaviruses and possesses an S gene that is genetically distinct from those of all known coronaviruses. In addition, the genome of WESV contains a distinct NS7 gene that exhibits no sequence similarity to those of any known viruses. Together, these data suggest that shrews are important and longstanding hosts for coronaviruses that merit additional research and surveillance.",,"['Wang, Wen', 'Lin, Xian-Dan', 'Liao, Yong', 'Guan, Xiao-Qing', 'Guo, Wen-Ping', 'Xing, Jian-Guang', 'Holmes, Edward C.', 'Zhang, Yong-Zhen']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.01105-17,PMC5553158,,,,,,,,,
,PMC,Identification and characterization of a long non-coding RNA up-regulated during HIV-1 infection,http://dx.doi.org/10.1016/j.virol.2017.08.006,PMC5623643,,,"Long non-coding RNAs (lncRNAs) are rapidly emerging as important regulators of a diverse array of cellular functions. Here, we describe a meta-analysis of two independent RNA-seq studies to identify lncRNAs that are differentially expressed upon HIV-1 infection. Only three lncRNA genes exhibited altered expression of ≥2-fold in HIV-1-infected cells. Of these, the uncharacterized lncRNA LINC00173 was chosen for further study. Both transcript variants of LINC00173 (lnc173 TSV1 and 2) could be detected by qPCR, localized predominantly to the nucleus and were reproducibly up-regulated during infection. Knock-out of the LINC00173 locus did not have detectable effects on HIV-1 replication. Interestingly, however, stimulation of Jurkat T cells with PMA/ionomycin resulted in a decrease of lnc173 expression, and Jurkat cells deficient for lnc173 on average expressed higher levels of specific cytokines than control cells. These data suggest that lnc173 may have a role in the regulation of cytokines in T cells.",,"['Postler, Thomas S.', 'Pantry, Shara N.', 'Desrosiers, Ronald C.', 'Ghosh, Sankar']",,,,
,PMC,Principles of Broad and Potent Antiviral Human Antibodies: Insights for Vaccine Design,http://dx.doi.org/10.1016/j.chom.2017.07.013,PMC5700460,,,"Antibodies are the principal immune effectors that mediate protection against reinfection following viral infection or vaccination. Robust techniques for human mAb isolation have been developed in the last decade. The study of human mAbs isolated from subjects with prior immunity has become a mainstay for rational structure-based, next-generation vaccine development. The plethora of detailed molecular and genetic studies coupling the structure of antigen-antibody complexes with their antiviral function has begun to reveal common principles of critical interactions on which we can build better vaccines and therapeutic antibodies. This review outlines the approaches to isolating and studying human antiviral mAbs and discusses the common principles underlying the basis for their activity. This review also examines progress toward the goal of achieving a comprehensive understanding of the chemical and physical basis for molecular recognition of viral surface proteins in order to build predictive molecular models that can be used for vaccine design.",,"Crowe, James E.",,,,
,PMC,Ten Strategies of Interferon Evasion by Viruses,http://dx.doi.org/10.1016/j.chom.2017.07.012,PMC5576560,,,"Viruses infecting vertebrate hosts must overcome the interferon (IFN)-mediated antiviral response to replicate and propagate to new hosts. The complex regulation of the IFN response allows viruses to antagonize IFN at multiple levels. However, no single strategy appears to be the golden ticket, and viruses have adopted multiple means to dampen this host defense. This review does not exhaustively cover all mechanisms of viral IFN antagonism. Rather it examines the ten most common strategies that viruses use to subvert the IFN response with examples from publications appearing in the last 10 years of Cell Host & Microbe. The virus-host interactions involved in induction and evasion of IFN represent a fertile area of research due to the significant large number of host and viral products that regulate this response, resulting in an intricate dance between hosts and their pathogens to achieve an optimal balance between virus replication, host disease and survival.",,"García-Sastre, Adolfo",,,,
,PMC,"Community-Acquired Pneumonia Visualized on CT Scans but Not Chest Radiographs: Pathogens, Severity, and Clinical Outcomes",http://dx.doi.org/10.1016/j.chest.2017.07.035,PMC5989638,,,"BACKGROUND: The clinical significance of pneumonia visualized on CT scan in the setting of a normal chest radiograph is uncertain. METHODS: In a multicenter prospective surveillance study of adults hospitalized with community-acquired pneumonia (CAP), we compared the presenting clinical features, pathogens present, and outcomes of patients with pneumonia visualized on a CT scan but not on a concurrent chest radiograph (CT-only pneumonia) and those with pneumonia visualized on a chest radiograph. All patients underwent chest radiography; the decision to obtain CT imaging was determined by the treating clinicians. Chest radiographs and CT images were interpreted by study-dedicated thoracic radiologists blinded to the clinical data. RESULTS: The study population included 2,251 adults with CAP; 2,185 patients (97%) had pneumonia visualized on chest radiography, whereas 66 patients (3%) had pneumonia visualized on CT scan but not on concurrent chest radiography. Overall, these patients with CT-only pneumonia had a clinical profile similar to those with pneumonia visualized on chest radiography, including comorbidities, vital signs, hospital length of stay, prevalence of viral (30% vs 26%) and bacterial (12% vs 14%) pathogens, ICU admission (23% vs 21%), use of mechanical ventilation (6% vs 5%), septic shock (5% vs 4%), and inhospital mortality (0 vs 2%). CONCLUSIONS: Adults hospitalized with CAP who had radiological evidence of pneumonia on CT scan but not on concurrent chest radiograph had pathogens, disease severity, and outcomes similar to patients who had signs of pneumonia on chest radiography. These findings support using the same management principles for patients with CT-only pneumonia and those with pneumonia seen on chest radiography.",,"['Upchurch, Cameron P.', 'Grijalva, Carlos G.', 'Wunderink, Richard G.', 'Williams, Derek J.', 'Waterer, Grant W.', 'Anderson, Evan J.', 'Zhu, Yuwei', 'Hart, Eric M.', 'Carroll, Frank', 'Bramley, Anna M.', 'Jain, Seema', 'Edwards, Kathryn M.', 'Self, Wesley H.']",,,,
,PMC,Analysis of tick-borne encephalitis virus-induced host responses in human cells of neuronal origin and interferon-mediated protection,http://dx.doi.org/10.1099/jgv.0.000853,PMC5817271,,,"Tick-borne encephalitis virus (TBEV) is a member of the genus Flavivirus. It can cause serious infections in humans that may result in encephalitis/meningoencephalitis. Although several studies have described the involvement of specific genes in the host response to TBEV infection in the central nervous system (CNS), the overall network remains poorly characterized. Therefore, we investigated the response of DAOY cells (human medulloblastoma cells derived from cerebellar neurons) to TBEV (Neudoerfl strain, Western subtype) infection to characterize differentially expressed genes by transcriptome analysis. Our results revealed a wide panel of interferon-stimulated genes (ISGs) and pro-inflammatory cytokines, including type III but not type I (or II) interferons (IFNs), which are activated upon TBEV infection, as well as a number of non-coding RNAs, including long non-coding RNAs. To obtain a broader view of the pathways responsible for eliciting an antiviral state in DAOY cells we examined the effect of type I and III IFNs and found that only type I IFN pre-treatment inhibited TBEV production. The cellular response to TBEV showed only partial overlap with gene expression changes induced by IFN-β treatment – suggesting a virus-specific signature – and we identified a group of ISGs that were highly up-regulated following IFN-β treatment. Moreover, a high rate of down-regulation was observed for a wide panel of pro-inflammatory cytokines upon IFN-β treatment. These data can serve as the basis for further studies of host–TBEV interactions and the identification of ISGs and/or lncRNAs with potent antiviral effects in cases of TBEV infection in human neuronal cells.",,"['Selinger, Martin', 'Wilkie, Gavin S.', 'Tong, Lily', 'Gu, Quan', 'Schnettler, Esther', 'Grubhoffer, Libor', 'Kohl, Alain']",,,,
,PMC,Effects of HIV-1 gp41-Derived Virucidal Peptides on Virus-like Lipid Membranes,http://dx.doi.org/10.1016/j.bpj.2017.06.061,PMC5607204,,,"Membrane fusion induced by the envelope glycoprotein enables the intracellular replication of HIV-1; hence, this process constitutes a major target for antiretroviral compounds. It has been proposed that peptides having propensity to interact with membrane interfaces might exert broad antiviral activity against enveloped viruses. To test this hypothesis, in this contribution we have analyzed the antiviral effects of peptides derived from the membrane-proximal external region and the transmembrane domain of the envelope glycoprotein subunit gp41, which display different degrees of interfacial hydrophobicity. Our data support the virucidal activity of a region that combines hydrophobic-at-interface membrane-proximal external region aromatics with hydrophobic residues of the transmembrane domain, and contains the absolutely conserved (679)LWYIK/R(683) sequence, proposed to embody a “cholesterol recognition/interaction amino acid consensus” motif. We further sought to correlate the antiviral activity of these peptides and their effects on membranes that mimic lipid composition and biophysical properties of the viral envelope. The data revealed that peptides endowed with virucidal activity were membrane active and induced permeabilization and fusion of virus-like lipid vesicles. In addition, they modulated lipid packing and miscibility of laterally segregated liquid domains, two properties that depend on the high cholesterol content of the viral membrane. Thus, the overall experimental evidence is consistent with a pattern of HIV inhibition that involves direct alteration of the physical chemistry of the virus membrane. Furthermore, the sequence-dependent effects observed might guide the development of new virucidal peptides.",,"['Carravilla, Pablo', 'Cruz, Antonio', 'Martin-Ugarte, Itziar', 'Oar-Arteta, Itziar R.', 'Torralba, Johanna', 'Apellaniz, Beatriz', 'Pérez-Gil, Jesús', 'Requejo-Isidro, José', 'Huarte, Nerea', 'Nieva, José L.']",,,,
,PMC,Mechanism of C5a-induced immunologic derangement in sepsis,http://dx.doi.org/10.1038/cmi.2017.68,PMC5596250,,,,,"['Xu, Ruonan', 'Lin, Fang', 'Bao, Chunmei', 'Wang, Fu-Sheng']",,,,
,PMC,Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies,http://dx.doi.org/10.1007/s10875-017-0426-2,PMC5693703,,,,,"['Sullivan, Kathleen E', 'Bassiri, Hamid', 'Bousfiha, Ahmed Aziz', 'Costa-Carvalho, Beatriz Tavares', 'Freeman, Alexandra F', 'Hagin, David', 'Lau, Yu Lung', 'Lionakis, Michail S.', 'Moreira, Ileana', 'Pinto, Jorge A.', 'de Moraes-Pinto, M. Isabel', 'Rawat, Amit', 'Reda, Shereen M.', 'Reyes, Saul Oswaldo Lugo', 'Seppänen, Oyl Mikko', 'Tang, Mimi LK']",,,,
,PMC,Supplemental Oxygen–Free Days in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus,http://dx.doi.org/10.1093/infdis/jix390,PMC5853655,,,"BACKGROUND: Clinically meaningful endpoints for respiratory syncytial virus (RSV) treatment trials are lacking for hematopoietic cell transplant (HCT) recipients. We evaluated supplemental oxygen use among HCT recipients with RSV infection. METHODS: Subjects were grouped according to the presence of upper respiratory tract infection (URTI) without lower respiratory tract infection (LRTI), URTI progressing to LRTI, and LRTI at presentation. LRTI was defined as a positive lower respiratory tract sample with or without radiographic abnormality (defined as proven or probable LRTI, respectively) or a positive upper respiratory tract sample with radiographic abnormality (possible LRTI). Supplemental oxygen–free days were defined as any day while alive after diagnosis of RSV infection during which ≤2 L of supplemental oxygen per minute was received. RESULTS: Among 230 patients, supplemental oxygen use by day 28 after the first diagnosis of RSV infection was lowest in patients presenting with URTI (31 of 197 [16%]). Supplemental oxygen use was lower in patients with possible LRTI (12 of 45 [27%]) than in those with proven/probable LRTI (29 of 42 [69%]). Patients presenting with proven/probable LRTI had a median of 16 fewer supplemental oxygen–free days than those presenting with URTI (P < .0001). Death only occurred among patients with proven/probable LRTI (11 of 42 [26%]). CONCLUSIONS: Confirmation of RSV infection in the lower respiratory tract provides prognostic information that may help prioritize therapies. Supplemental oxygen–free days as a clinical endpoint may allow smaller sample sizes for trials evaluating RSV antivirals.",,"['Waghmare, Alpana', 'Xie, Hu', 'Kimball, Louise', 'Yi, Jessica', 'Özkök, Sezen', 'Leisenring, Wendy', 'Cheng, Guang-Shing', 'Englund, Janet A', 'Watkins, Timothy R', 'Chien, Jason W', 'Boeckh, Michael']",,,,
,PMC,Using Homology Modeling to Interrogate Binding Affinity in Neutralization of Ricin Toxin by a Family of Single Domain Antibodies,http://dx.doi.org/10.1002/prot.25353,PMC5754017,,,"In this report we investigated, within a group of closely related single domain camelid antibodies (V(H)Hs), the relationship between binding affinity and neutralizing activity as it pertains to ricin, a fast-acting toxin and biothreat agent. The V1C7-like V(H)Hs (V1C7, V2B9, V2E8, and V5C1) are similar in amino acid sequence, but differ in their binding affinities and toxin-neutralizing activities. Using the X-ray crystal structure of V1C7 in complex with ricin’s enzymatic subunit (RTA) as a template, Rosetta-based homology modeling coupled with energetic decomposition led us to predict that a single pairwise interaction between Arg29 on V5C1 and Glu67 on RTA was responsible for the difference in ricin toxin binding affinity between V1C7, a weak neutralizer, and V5C1, a moderate neutralizer. This prediction was borne out experimentally: substitution of Arg for Gly at position 29 enhanced V1C7’s binding affinity for ricin, whereas the reverse (i.e., Gly for Arg at position 29) diminished V5C1’s binding affinity by >10 fold. As expected, the V5C1(R29G) mutant was largely devoid of toxin-neutralizing activity. However, the toxin-neutralizing activity of the V1C7(G29R) mutant was not correspondingly improved, indicating that in the V1C7 family binding affinity alone does not account for differences in antibody function. V1C7 and V5C1, as well as their respective point mutants, recognized indistinguishable epitopes on RTA, at least at the level of sensitivity afforded by hydrogen-deuterium mass spectrometry. The results of this study have implications for engineering therapeutic antibodies because they demonstrate that even subtle differences in epitope specificity can account for important differences in antibody function.",,"['Bazzoli, Andrea', 'Vance, David J.', 'Rudolph, Michael J.', 'Rong, Yinghui', 'Angalakurthi, Siva Krishna', 'Toth, Ronald T.', 'Middaugh, C. Russell', 'Volkin, David B.', 'Weis, David D.', 'Karanicolas, John', 'Mantis, Nicholas J.']",,,,
,PMC,Recovery from the Middle East Respiratory Syndrome is Associated with Antibody and T Cell Responses(),http://dx.doi.org/10.1126/sciimmunol.aan5393,PMC5576145,,,"The Middle East Respiratory Syndrome-coronavirus (MERS-CoV) causes a highly lethal pneumonia. MERS was recently identified as a candidate for vaccine development but most efforts focus on antibody responses, which are often transient after CoV infections. CoV-specific T cells are generally long-lived but the virus-specific T cell response has not been addressed in MERS patients. Here, we obtained PBMCs and/or sera from 21 MERS survivors. We detected MERS-CoV-specific CD4 and CD8 T cell responses in all MERS survivors and demonstrated functionality by measuring cytokine expression after peptide stimulation. Neutralizing (PRNT(50)) antibody titers measured in vitro predicted serum protective ability in infected mice and correlated with CD4 but not CD8 T cell responses; patients with higher PRNT(50) and CD4 T cell responses had longer ICU stays and prolonged virus shedding and required ventilation. Survivors with undetectable MERS-CoV-specific antibody responses mounted CD8 T cell responses comparable to those of the whole cohort. There were no correlations between age, disease severity, co-morbidities and virus-specific CD8 T cell responses. In conclusion, measurements of MERS-CoV-specific T cell responses may be useful for predicting prognosis, monitoring vaccine efficacy and identifying MERS patients with mild disease in epidemiological studies and will complement virus-specific antibody measurements.",,"['Zhao, Jingxian', 'Alshukairi, Abeer N.', 'Baharoon, Salim A.', 'Ahmed, Waleed A.', 'Bokhari, Ahmad A.', 'Nehdi, Atef M.', 'Layqah, Laila A.', 'Alghamdi, Mohammed G.', 'Al Gethamy, Manal M.', 'Dada, Ashraf M.', 'Khalid, Imran', 'Boujelal, Mohamad', 'Al Johani, Sameera M.', 'Vogel, Leatrice', 'Subbarao, Kanta', 'Mangalam, Ashutosh', 'Wu, Chaorong', 'Eyck, Patrick Ten', 'Perlman, Stanley', 'Zhao, Jincun']",,,,
,PMC,Influenza virus infection alters ion channel function of airway and alveolar cells: mechanisms and physiological sequelae,http://dx.doi.org/10.1152/ajplung.00244.2017,PMC5792181,,,"The cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channels (ENaC) are located in the apical membranes of airway and alveolar epithelial cells. These transporters play an important role in the regulation of lung fluid balance across airway and alveolar epithelia by being the conduits for chloride (Cl(−)) and bicarbonate ([Formula: see text]) secretion and sodium (Na(+)) ion absorption, respectively. The functional role of these channels in the respiratory tract is to maintain the optimum volume and ionic composition of the bronchial periciliary fluid (PCL) and alveolar lining fluid (ALF) layers. The PCL is required for proper mucociliary clearance of pathogens and debris, and the ALF is necessary for surfactant homeostasis and optimum gas exchange. Dysregulation of ion transport may lead to mucus accumulation, bacterial infections, inflammation, pulmonary edema, and compromised respiratory function. Influenza (or flu) in mammals is caused by influenza A and B viruses. Symptoms include dry cough, sore throat, and is often followed by secondary bacterial infections, accumulation of fluid in the alveolar spaces and acute lung injury. The underlying mechanisms of flu symptoms are not fully understood. This review summarizes our present knowledge of how influenza virus infections alter airway and alveolar epithelial cell CFTR and ENaC function in vivo and in vitro and the role of these changes in influenza pathogenesis.",,"['Londino, James David', 'Lazrak, Ahmed', 'Collawn, James F.', 'Bebok, Zsuzsanna', 'Harrod, Kevin S.', 'Matalon, Sadis']",,,,
,PMC,"Preventative effects of a HIF inhibitor, 17-DMAG, on partial bladder outlet obstruction-induced bladder dysfunction",http://dx.doi.org/10.1152/ajprenal.00240.2017,PMC6148299,,,"Posterior urethral valves are the most common cause of partial bladder outlet obstruction (PBOO) in the pediatric population. Pathological changes in the bladder developed during PBOO are responsible for long-lasting voiding dysfunction in this population despite early surgical interventions. Increasing evidence showed PBOO induces an upregulation of hypoxia-inducible factors (HIFs) and their transcriptional target genes, and they play a role in pathophysiological changes in the obstructed bladders. We hypothesized that blocking HIF pathways can prevent PBOO-induced bladder dysfunction. PBOO was surgically created by ligation of the bladder neck in male C57BL/6J mice for 2 wk. PBOO mice received intraperitoneal injection of either saline or 17-DMAG (alvespimycin, 3 mg/kg) every 48 h starting from day 1 postsurgery. Sham-operated animals received injection of saline on the same schedule as PBOO mice and served as controls. The bladders were harvested after 2 wk, and basal activity and evoked contractility of the detrusor smooth muscle (DSM) were evaluated in vitro. Bladder function was assessed in vivo by void spot assay and cystometry in conscious, unrestrained mice. Results indicated the 17-DMAG treatment preserved DSM contractility and partially prevented the development of detrusor over activity in obstructed bladders. In addition, PBOO caused a significant increase in the frequency of micturition, which was significantly reduced by 17-DMAG treatment. The 17-DMAG treatment improved urodynamic parameters, including increases in the bladder pressure at micturition and nonvoid contractions observed in PBOO mice. These results demonstrate that treatment with 17-DMAG, a HIF inhibitor, significantly alleviated PBOO-induced bladder pathology in vivo.",,"['Iguchi, Nao', 'Dönmez, M. İrfan', 'Malykhina, Anna P.', 'Carrasco, Alonso', 'Wilcox, Duncan T.']",,,,
,PMC,Human Airway Epithelial Cells Direct Significant Rhinovirus Replication in Monocytic Cells by Enhancing ICAM1 Expression,http://dx.doi.org/10.1165/rcmb.2016-0271OC,PMC5576581,,,"Human rhinovirus (RV) is the major cause of common cold, and it also plays a significant role in asthma and asthma exacerbation. The airway epithelium is the primary site of RV infection and production. In contrast, monocytic cells (e.g., monocytes and macrophages) are believed to be nonpermissive for RV replication. Instead, RV has been shown to modulate inflammatory gene expressions in these cells via a replication-independent mechanism. In the study presented here, replication of RV16 (a major-group RV) was found to be significantly enhanced in monocytes when it was cocultivated with airway epithelial cells. This effect appeared to be mediated by secretory components from epithelial cells, which stimulated RV16 replication and significantly elevated the expression of a number of proinflammatory cytokines. The lack of such an effect on RV1A, a minor-group RV that enters the cell by a different receptor, suggests that intercellular adhesion molecule 1 (ICAM1), the receptor for major-group RVs, may be involved. Indeed, conditioned media from epithelial cells significantly increased ICAM1 expression in monocytes. Consistently, ICAM1 overexpression and ICAM1 knockdown enhanced and blocked RV production, respectively, confirming the role of ICAM1 in this process. Thus, this is the first report demonstrating that airway epithelial cells direct significant RV16 replication in monocytic cells via an ICAM1-dependent mechanism. This finding will open a new avenue for the study of RV infection in airway disease and its exacerbation.",,"['Zhou, Xu', 'Zhu, Lingxiang', 'Lizarraga, Rosa', 'Chen, Yin']",,,,
,PMC,Comparative efficacy of intranasal and injectable vaccines in stimulating Bordetella bronchiseptica-reactive anamnestic antibody responses in household dogs,,PMC5508940,,,"In order to determine the comparative efficacy of injectable and intranasal vaccines to stimulate Bordetella bronchiseptica (Bb)-reactive anamnestic antibodies, a trial was conducted using 144 adult household dogs of various breeds and ages, which had been previously administered intranasal Bb vaccine approximately 12 months before enrollment. Dogs were randomized into 2 groups and blood, nasal swabs, and pharyngeal swabs were collected prior to the administration of single component Bb vaccines intranasally or parenterally. Ten to 14 days later all dogs were resampled to measure changes in systemic and local antibody to Bb. There were no differences in the changes in Bb-reactive serum IgG and nasal IgA between the groups, whereas intranasally vaccinated dogs had significantly higher Bb-reactive serum IgA. These data indicate that both of the current generation of intranasal (modified-live) and injectable (acellular) Bb vaccines can stimulate anamnestic local and systemic antibody responses in previously vaccinated, Bb-seropositive adult household dogs.",,"['Ellis, John A.', 'Gow, Sheryl P.', 'Lee, Lindsey B.', 'Lacoste, Stacey', 'Ball, Eileen C.']",,,,
,PMC,The UK’s multidisciplinary response to an Ebola epidemic,http://dx.doi.org/10.7861/clinmedicine.17-4-332,PMC6297657,,,"The West African Ebola virus disease (EVD) epidemic was the largest and most devastating outbreak of EVD the world has ever seen. Its impact was felt far from the shores of Guinea, Liberia and Sierra Leone, with public health systems and clinicians across the globe confronted with an international response both in the affected region and within their own borders. The UK had a prominent role in response efforts, particularly in Sierra Leone. This article highlights how UK academic, health service, military, commercial and public health professionals all played a significant role both at home and abroad.",,"['Reece, Sian', 'Brown, Colin S', 'Dunning, Jake', 'Chand, Meera A', 'Zambon, Maria C', 'Jacobs, Michael']",,,,
,PMC,Generation of Recombinant Vaccinia Viruses,http://dx.doi.org/10.1002/cpps.33,PMC5765993,,,"This unit describes how to infect cells with vaccinia virus and then transfect them with a plasmid-transfer vector or PCR fragment to generate a recombinant virus. Selection and screening methods used to isolate recombinant viruses and a method for the amplification of recombinant viruses are described. Finally, a method for live immunostaining that has been used primarily for detection of recombinant modified vaccinia virus Ankara (MVA) is presented.",,"['Earl, Patricia L.', 'Moss, Bernard', 'Wyatt, Linda S.']",,,,
,PMC,New Frontiers of Basic Science Research in Neurogenic Lower Urinary Tract Dysfunction,http://dx.doi.org/10.1016/j.ucl.2017.04.014,PMC5647782,,,"The lower urinary tract has two main functions, storage and elimination. The micturition reflex is one of the autonomic reflexes mediated by the spinobulbospinal reflex pathway that passes through the pontine micturition center. This reflex pathway is in turn modulated by higher centers in the cerebral cortex that are involved in the voluntary control of micturition. Due to the complexity of the neural control of lower urinary tract, micturition is sensitive to numerous injuries, such as spinal cord injury, cerebral infarction, Parkinson’s disease, multiple sclerosis and spina bifida, which result in various types of neurogenic lower urinary tract dysfunction. Studies in animals for these diseases involved in the central nervous system indicate that the lower urinary tract dysfunction is dependent in part on plasticity of the neural pathways controlling the lower urinary tract. Reflex plasticity is also associated with changes in the properties of ion channels, receptors, and numerous mediators. These animal models may help to investigate the mechanism involved in the genesis of pathological conditions as well as the plasticity in reflex pathways to the lower urinary tract after neurogenic lesions.",,"['Miyazato, Minoru', 'Kadekawa, Katsumi', 'Kitta, Takeya', 'Wada, Naoki', 'Shimizu, Nobutaka', 'de Groat, William C.', 'Birder, Lori A.', 'Kanai, Anthony J.', 'Saito, Seiichi', 'Yoshimura, Naoki']",,,,
,PMC,Characterization of Aerosols Generated During Patient Care Activities,http://dx.doi.org/10.1093/cid/cix535,PMC6248660,,,"BACKGROUND: Questions remain about the degree to which aerosols are generated during routine patient care activities and whether such aerosols could transmit viable pathogens to healthcare personnel (HCP). The objective of this study was to measure aerosol production during multiple patient care activities and to examine the samples for bacterial pathogens. METHODS: Five aerosol characterization instruments were used to measure aerosols during 7 patient care activities: patient bathing, changing bed linens, pouring and flushing liquid waste, bronchoscopy, noninvasive ventilation, and nebulized medication administration (NMA). Each procedure was sampled 5 times. An SKC BioSampler was used for pathogen recovery. Bacterial cultures were performed on the sampling solution. Patients on contact precautions for drug-resistant organisms were selected for most activity sampling. Any patient undergoing bronchoscopy was eligible. RESULTS: Of 35 sampling episodes, only 2 procedures showed a significant increase in particle concentrations over baseline: NMA and bronchoscopy with NMA. Bronchoscopy without NMA and noninvasive ventilation did not generate significant aerosols. Of 78 cultures from the impinger samples, 6 of 28 baseline samples (21.4%) and 14 of 50 procedure samples (28.0%) were positive. CONCLUSIONS: In this study, significant aerosol generation was only observed during NMA, both alone and during bronchoscopy. Minimal viable bacteria were recovered, mostly common environmental organisms. Although more research is needed, these data suggest that some of the procedures considered to be aerosol-generating may pose little infection risk to HCP.",,"['O’Neil, Caroline A', 'Li, Jiayu', 'Leavey, Anna', 'Wang, Yang', 'Hink, Matthew', 'Wallace, Meghan', 'Biswas, Pratim', 'Burnham, Carey-Ann D', 'Babcock, Hilary M', None]",,,,
,PMC,DNA prime/protein boost vaccination elicits robust humoral response in rhesus macaques using oligomeric simian immunodeficiency virus envelope and Advax delta inulin adjuvant,http://dx.doi.org/10.1099/jgv.0.000863,PMC5817272,,,"The partial success of the RV144 trial underscores the importance of envelope-specific antibody responses for an effective HIV-1 vaccine. Oligomeric HIV-1 envelope proteins delivered with a potent adjuvant are expected to elicit strong antibody responses with broad neutralization specificity. To test this hypothesis, two SIV envelope proteins were formulated with delta inulin-based adjuvant (Advax) and used to immunize nonhuman primates. Oligomeric gp140–gp145 from SIVmac251 and SIVsmE660 was purified to homogeneity. Oligomers showed high-affinity interaction with CD4 and were highly immunogenic in rabbits, inducing Tier 2 SIV-neutralizing antibodies. The immunogenicity of an oligomeric Env DNA prime and protein boost together with Advax was evaluated in Chinese rhesus macaques. DNA administration elicited antibodies to both envelopes, and titres were markedly enhanced following homologous protein boosts via intranasal and intramuscular routes. Strong antibody responses were detected against the V1 and V2 domains of gp120. During peak immune responses, a low to moderate level of neutralizing activity was detected against Tier 1A/1B SIV isolates, with a moderate level noted against a Tier 2 isolate. Increased serum antibody affinity to SIVmac251 gp140 and generation of Env-specific memory B cells were observed in the immunized macaques. Animals were subjected to low-dose intravaginal challenge with SIVmac251 one week after the last protein boost. One out of three immunized animals was protected from infection. Although performed with a small number of macaques, this study demonstrates the utility of oligomeric envelopes formulated with Advax in eliciting broad antibody responses with the potential to provide protection against SIV transmission.",,"['Menon, Veena', 'Ayala, Victor I.', 'Rangaswamy, Sneha P.', 'Kalisz, Irene', 'Whitney, Stephen', 'Galmin, Lindsey', 'Ashraf, Asma', 'LaBranche, Celia', 'Montefiori, David', 'Petrovsky, Nikolai', 'Kalyanaraman, Vaniambadi S.', 'Pal, Ranajit']",,,,
,PMC,Personalized Vaccinology: A Review,http://dx.doi.org/10.1016/j.vaccine.2017.07.062,PMC5792371,,,"At the current time, the field of vaccinology remains empirical in many respects. Vaccine development, vaccine immunogenicity, and vaccine efficacy have, for the most part, historically been driven by an empiric “isolate-inactivate-inject” paradigm. In turn, a population-level public health paradigm of “the same dose for everyone for every disease” model has been the normative thinking in regard to prevention of vaccine-preventable infectious diseases. In addition, up until recently, no vaccines specifically had been designed to overcome the immunosenescence of aging, consistent with a post-WWII mentality of developing vaccines and vaccine programs for children. It is now recognized that the current lack of knowledge concerning how immune responses to vaccines are generated is a critical barrier to understanding poor vaccine responses in the elderly and in immunoimmaturity, discovery of new correlates of vaccine immunogenicity (vaccine response biomarkers), and a directed approach to new vaccine development. The new fields of vaccinomics and adversomics provide models that permit global profiling of the innate, humoral, and cellular immune responses integrated at a systems biology level. This has advanced the science beyond that of reductionist scientific approaches by revealing novel interactions between and within the immune system and other biological systems (beyond transcriptional level), which are critical to developing “downstream” adaptive humoral and cellular responses to infectious pathogens and vaccines. Others have applied systems level approaches to the study of antibody responses (a.k.a. “systems serology”), [1] high dimensional cell subset immunophenotyping through CyTOF, [2, 3] and vaccine induced metabolic changes [4]. In turn, this knowledge is being utilized to better understand the following: identifying who is at risk for which infections; the level of risk that exists regarding poor immunogenicity and/or serious adverse events; and the type or dose of vaccine needed to fully protect an individual. In toto, such approaches allow for a personalized approach to the practice of vaccinology, analogous to the substantial inroads that individualized medicine is playing in other fields of human health and medicine. Herein we briefly review the field of vaccinomics, adversomics, and personalized vaccinology.",,"['Poland, GA', 'Ovsyannikova, IG', 'Kennedy, RB']",,,,
,PMC,Pathogen‐reduced platelets for the prevention of bleeding,http://dx.doi.org/10.1002/14651858.CD009072.pub3,PMC5558872,,,"BACKGROUND: Platelet transfusions are used to prevent and treat bleeding in people who are thrombocytopenic. Despite improvements in donor screening and laboratory testing, a small risk of viral, bacterial, or protozoal contamination of platelets remains. There is also an ongoing risk from newly emerging blood transfusion‐transmitted infections for which laboratory tests may not be available at the time of initial outbreak. One solution to reduce the risk of blood transfusion‐transmitted infections from platelet transfusion is photochemical pathogen reduction, in which pathogens are either inactivated or significantly depleted in number, thereby reducing the chance of transmission. This process might offer additional benefits, including platelet shelf‐life extension, and negate the requirement for gamma‐irradiation of platelets. Although current pathogen‐reduction technologies have been proven to reduce pathogen load in platelet concentrates, a number of published clinical studies have raised concerns about the effectiveness of pathogen‐reduced platelets for post‐transfusion platelet count recovery and the prevention of bleeding when compared with standard platelets. This is an update of a Cochrane review first published in 2013. OBJECTIVES: To assess the effectiveness of pathogen‐reduced platelets for the prevention of bleeding in people of any age requiring platelet transfusions. SEARCH METHODS: We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 9), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 24 October 2016. SELECTION CRITERIA: We included RCTs comparing the transfusion of pathogen‐reduced platelets with standard platelets, or comparing different types of pathogen‐reduced platelets. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified five new trials in this update of the review. A total of 15 trials were eligible for inclusion in this review, 12 completed trials (2075 participants) and three ongoing trials. Ten of the 12 completed trials were included in the original review. We did not identify any RCTs comparing the transfusion of one type of pathogen‐reduced platelets with another. Nine trials compared Intercept® pathogen‐reduced platelets to standard platelets, two trials compared Mirasol® pathogen‐reduced platelets to standard platelets; and one trial compared both pathogen‐reduced platelets types to standard platelets. Three RCTs were randomised cross‐over trials, and nine were parallel‐group trials. Of the 2075 participants enrolled in the trials, 1981 participants received at least one platelet transfusion (1662 participants in Intercept® platelet trials and 319 in Mirasol® platelet trials). One trial included children requiring cardiac surgery (16 participants) or adults requiring a liver transplant (28 participants). All of the other participants were thrombocytopenic individuals who had a haematological or oncological diagnosis. Eight trials included only adults. Four of the included studies were at low risk of bias in every domain, while the remaining eight included studies had some threats to validity. Overall, the quality of the evidence was low to high across different outcomes according to GRADE methodology. We are very uncertain as to whether pathogen‐reduced platelets increase the risk of any bleeding (World Health Organization (WHO) Grade 1 to 4) (5 trials, 1085 participants; fixed‐effect risk ratio (RR) 1.09, 95% confidence interval (CI) 1.02 to 1.15; I(2) = 59%, random‐effect RR 1.14, 95% CI 0.93 to 1.38; I(2) = 59%; low‐quality evidence). There was no evidence of a difference between pathogen‐reduced platelets and standard platelets in the incidence of clinically significant bleeding complications (WHO Grade 2 or higher) (5 trials, 1392 participants; RR 1.10, 95% CI 0.97 to 1.25; I(2) = 0%; moderate‐quality evidence), and there is probably no difference in the risk of developing severe bleeding (WHO Grade 3 or higher) (6 trials, 1495 participants; RR 1.24, 95% CI 0.76 to 2.02; I(2) = 32%; moderate‐quality evidence). There is probably no difference between pathogen‐reduced platelets and standard platelets in the incidence of all‐cause mortality at 4 to 12 weeks (6 trials, 1509 participants; RR 0.81, 95% CI 0.50 to 1.29; I(2) = 26%; moderate‐quality evidence). There is probably no difference between pathogen‐reduced platelets and standard platelets in the incidence of serious adverse events (7 trials, 1340 participants; RR 1.09, 95% CI 0.88 to 1.35; I(2) = 0%; moderate‐quality evidence). However, no bacterial transfusion‐transmitted infections occurred in the six trials that reported this outcome. Participants who received pathogen‐reduced platelet transfusions had an increased risk of developing platelet refractoriness (7 trials, 1525 participants; RR 2.94, 95% CI 2.08 to 4.16; I(2) = 0%; high‐quality evidence), though the definition of platelet refractoriness differed between trials. Participants who received pathogen‐reduced platelet transfusions required more platelet transfusions (6 trials, 1509 participants; mean difference (MD) 1.23, 95% CI 0.86 to 1.61; I(2) = 27%; high‐quality evidence), and there was probably a shorter time interval between transfusions (6 trials, 1489 participants; MD ‐0.42, 95% CI ‐0.53 to ‐0.32; I(2) = 29%; moderate‐quality evidence). Participants who received pathogen‐reduced platelet transfusions had a lower 24‐hour corrected‐count increment (7 trials, 1681 participants; MD ‐3.02, 95% CI ‐3.57 to ‐2.48; I(2) = 15%; high‐quality evidence). None of the studies reported quality of life. We did not evaluate any economic outcomes. There was evidence of subgroup differences in multiple transfusion trials between the two pathogen‐reduced platelet technologies assessed in this review (Intercept® and Mirasol®) for all‐cause mortality and the interval between platelet transfusions (favouring Intercept®). AUTHORS' CONCLUSIONS: Findings from this review were based on 12 trials, and of the 1981 participants who received a platelet transfusion only 44 did not have a haematological or oncological diagnosis. In people with haematological or oncological disorders who are thrombocytopenic due to their disease or its treatment, we found high‐quality evidence that pathogen‐reduced platelet transfusions increase the risk of platelet refractoriness and the platelet transfusion requirement. We found moderate‐quality evidence that pathogen‐reduced platelet transfusions do not affect all‐cause mortality, the risk of clinically significant or severe bleeding, or the risk of a serious adverse event. There was insufficient evidence for people with other diagnoses. All three ongoing trials are in adults (planned recruitment 1375 participants) with a haematological or oncological diagnosis.",,"['Estcourt, Lise J', 'Malouf, Reem', 'Hopewell, Sally', 'Trivella, Marialena', 'Doree, Carolyn', 'Stanworth, Simon J', 'Murphy, Michael F']",,,,
,PMC,Coexistence of multiple genotypes of porcine epidemic diarrhea virus with novel mutant S genes in the Hubei Province of China in 2016,http://dx.doi.org/10.1007/s12250-017-4021-8,PMC6599178,,,"The emergence of highly virulent porcine epidemic diarrhea virus (PEDV) variants in China caused huge economic losses in 2010. Since then, large-scale sporadic outbreaks of PED caused by PEDV variants have occasionally occurred in China. However, the molecular diversity and epidemiology of PEDV in different provinces has not been completely understood. To determine the molecular diversity of PEDV in the Hubei Province of China, we collected 172 PED samples from 34 farms across the province in 2016 and performed reverse transcription polymerase chain reaction (RT-PCR) by targeting the nucleocapsid (N) gene. Seventy-four samples were found to be PEDV-positive. We further characterized the complete spike (S) glycoprotein genes from the positive samples and found 21 different S genes with amino acid mutations. The PEDV isolates here presented most of the genotypes which were found previously in field isolates in East and South-East Asia, North America, and Europe. Besides the typical Genotypes I and II, the INDEX groups were also found. Importantly, 58 new amino acids mutant sites in the S genes, including 44 sites in S1 and 14 sites in S2, were first described. Our results revealed that the S genes of PEDV showed variation and that diverse genotypes of PEDV coexisted and were responsible for the PED outbreaks in Hubei in 2016. This work highlighted the complexity of the epidemiology of PEDV and emphasized the need for reassessing the efficacy of classic PEDV vaccines against emerging variant strains and developing new vaccines to facilitate the prevention and control of PEDV in fields. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s12250-017-4021-8 and is accessible for authorized users.",,"['Zeng, Zhe', 'Li, Ting-Ting', 'Jin, Xin', 'Peng, Fu-Hu', 'Song, Nian-Hua', 'Peng, Gui-Qing', 'Ge, Xing-Yi']",,,,
,PMC,Efficacy of Rhesus Theta-Defensin-1 in Experimental Models of Pseudomonas aeruginosa Lung Infection and Inflammation,http://dx.doi.org/10.1128/AAC.00154-17,PMC5527632,,,"Chronic airway infection and inflammation contribute to the progressive loss of lung function and shortened survival of patients with cystic fibrosis (CF). Rhesus theta defensin-1 (RTD-1) is a macrocyclic host defense peptide with antimicrobial and immunomodulatory activities. Combined with favorable preclinical safety and peptide stability data, RTD-1 warrants investigation to determine its therapeutic potential for treatment of CF lung disease. We sought to evaluate the therapeutic potential of RTD-1 for CF airway infection and inflammation using in vitro, ex vivo, and in vivo models. We evaluated RTD-1's effects on basal and Pseudomonas aeruginosa-induced inflammation in CF sputum leukocytes and CF bronchial epithelial cells. Peptide stability was evaluated by incubation with CF sputum. Airway pharmacokinetics, safety, and tolerance studies were performed in naive mice. Aerosolized RTD-1 treatment effects were assessed by analyzing lung bacterial burdens and airway inflammation using an established model of chronic P. aeruginosa endobronchial infection in CF (ΔF508) mice. RTD-1 directly reduces metalloprotease activity, as well as inflammatory cytokine secretion from CF airway leukocyte and bronchial epithelial cells. Intrapulmonary safety, tolerability, and stability data support the aerosol administration route. RTD-1 reduced the bacterial lung burden, airway neutrophils, and inflammatory cytokines in CF mice with chronic P. aeruginosa lung infection. Collectively, these studies support further development of RTD-1 for treatment of CF airway disease.",,"['Bensman, Timothy J.', 'Jayne, Jordanna G.', 'Sun, Meiling', 'Kimura, Elza', 'Meinert, Joshua', 'Wang, Joshua C.', 'Schaal, Justin B.', 'Tran, Dat', 'Rao, Adupa P.', 'Akbari, Omid', 'Selsted, Michael E.', 'Beringer, Paul M.']",,,,
,PMC,Evaluation of a Real-Time Reverse Transcription-PCR (RT-PCR) Assay for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Clinical Samples from an Outbreak in South Korea in 2015,http://dx.doi.org/10.1128/JCM.00667-17,PMC5527434,,,,,"['Lee, Jee-Soo', 'Ahn, Ji Soo', 'Yu, Byeong Su', 'Cho, Sung Im', 'Kim, Man Jin', 'Choi, Jong Moon', 'Seo, Soo Hyun', 'Park, Sung Sup', 'Seong, Moon-Woo']",,,,
,PMC,The Brief Case: False-Positive Rapid Malaria Antigen Test Result in a Returned Traveler,http://dx.doi.org/10.1128/JCM.02347-16,PMC5527405,,,,,"['Haberichter, Kristle L.', 'Johnson, Paul C.', 'Chittick, Paul J.', 'Millward, Peter', 'Robinson-Dunn, Barbara', 'Boyanton, Bobby L.']",,,,
,PMC,Immunologic Profiling of Human Metapneumovirus for the Development of Targeted Immunotherapy,http://dx.doi.org/10.1093/infdis/jix358,PMC5853664,,,"Human metapneumovirus (hMPV) is a respiratory virus detected in ≥9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon γ, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets. The detection of hMPV-specific T cells in HSCT recipients who endogenously controlled active infections support the clinical importance of T-cell immunity in mediating protective antiviral effects. Our results demonstrate the feasibility of developing an immunotherapy for immunocompromised patients with uncontrolled infections.",,"['Tzannou, Ifigeneia', 'Nicholas, Sarah K', 'Lulla, Premal', 'Aguayo-Hiraldo, Paibel I', 'Misra, Anisha', 'Martinez, Caridad A', 'Machado, Annette A', 'Orange, Jordan S', 'Piedra, Pedro A', 'Vera, Juan F', 'Leen, Ann M']",,,,
,PMC,Homology Modeling and Protein Interaction Map of CHRNA7 Neurogenesis Protein,http://dx.doi.org/10.1159/000477155,PMC5566677,,,"CHRNA7 is a neurodevelopmental protein involved in differentiation and neurogenesis, which is also named as nicotinic acetylcholine receptors, cholinergic receptor, nicotinic, alpha 7 (neuronal). The protein encoded by this gene forms a homo-oligomeric channel. It is a major component of brain nicotinic receptors displays that are blocked by and sensitive to alpha-bungarotoxin. Studies reports involvement of CHRNA7 protein in different neurological diseases. Non-availability of 3-dimensional (3D) structure leads the study toward structure 3D prediction along with its interaction analysis. The current paper is focused on the structure prediction through homology modeling of CHRNA7 along with binding site prediction using Schrödinger software suite. In continuation of the study, protein-protein interaction analysis is carried out by using string database. Tertiary structure along with binding sites was obtained, and visualized CHRAN7 protein have interaction with CHRNA protein family along with JAK2, AKT1, PICK1 protein that are involved in neurological disease. Structure formation analysis is an important aspect of proteomics studies. Hence, this predicted structure can be used for further advance studies and drug designing. Protein interaction analysis shows that CHRNA7 protein also interact with AKT1 protein which regulate neuronal differentiation and development, that signifies the role of CHRNA7 protein in neurological diseases.",,"['Yadav, Ruchi', 'Deepshikha, Deepshikha', 'Srivastava, Prachi']",,,,
,PMC,Evaluation of a Bead-Free Coimmunoprecipitation Technique for Identification of Virus–Host Protein Interactions Using High-Resolution Mass Spectrometry,http://dx.doi.org/10.7171/jbt.17-2803-002,PMC5524270,,,"Protein interactions between virus and host are essential for viral propagation and movement, as viruses lack most of the proteins required to thrive on their own. Precision methods aimed at disrupting virus–host interactions represent new approaches to disease management but require in-depth knowledge of the identity and binding specificity of host proteins within these interaction networks. Protein coimmunoprecipitation (co-IP) coupled with mass spectrometry (MS) provides a high-throughput way to characterize virus–host interactomes in a single experiment. Common co-IP methods use antibodies immobilized on agarose or magnetic beads to isolate virus–host complexes in solutions of host tissue homogenate. Although these workflows are well established, they can be fairly laborious and expensive. Therefore, we evaluated the feasibility of using antibody-coated microtiter plates coupled with MS analysis as an easy, less expensive way to identify host proteins that interact with Potato leafroll virus (PLRV), an insect-borne RNA virus that infects potatoes. With the use of the bead-free platform, we were able to detect 36 plant and 1 nonstructural viral protein significantly coimmunoprecipitating with PLRV. Two of these proteins, a 14-3-3 signal transduction protein and malate dehydrogenase 2 (mMDH2), were detected as having a weakened or lost association with a structural mutant of the virus, demonstrating that the bead-free method is sensitive enough to detect quantitative differences that can be used to pin-point domains of interaction. Collectively, our analysis shows that the bead-free platform is a low-cost alternative that can be used by core facilities and other investigators to identify plant and viral proteins interacting with virions and/or the viral structural proteins.",,"['DeBlasio, Stacy L.', 'Bereman, Michael S.', 'Mahoney, Jaclyn', 'Thannhauser, Theodore W.', 'Gray, Stewart M.', 'MacCoss, Michael J.', '(Cilia) Heck, Michelle']",,,,
,PMC,Lymphocytes transiently expressing virus-specific T cell receptors reduce hepatitis B virus infection,http://dx.doi.org/10.1172/JCI93024,PMC5531408,,,"Adoptive transfer of T cells engineered to express a hepatitis B virus–specific (HBV-specific) T cell receptor (TCR) may supplement HBV-specific immune responses in chronic HBV patients and facilitate HBV control. However, the risk of triggering unrestrained proliferation of permanently engineered T cells raises safety concerns that have hampered testing of this approach in patients. The aim of the present study was to generate T cells that transiently express HBV-specific TCRs using mRNA electroporation and to assess their antiviral and pathogenetic activity in vitro and in HBV-infected human liver chimeric mice. We assessed virological and gene-expression changes using quantitative reverse-transcriptase PCR (qRT-PCR), immunofluorescence, and Luminex technology. HBV-specific T cells lysed HBV-producing hepatoma cells in vitro. In vivo, 3 injections of HBV-specific T cells caused progressive viremia reduction within 12 days of treatment in animals reconstituted with haplotype-matched hepatocytes, whereas viremia remained stable in mice receiving irrelevant T cells redirected toward hepatitis C virus–specific TCRs. Notably, increases in alanine aminotransferase levels, apoptotic markers, and human inflammatory cytokines returned to pretreatment levels within 9 days after the last injection. T cell transfer did not trigger inflammation in uninfected mice. These data support the feasibility of using mRNA electroporation to engineer HBV TCR–redirected T cells in patients with chronic HBV infection.",,"['Kah, Janine', 'Koh, Sarene', 'Volz, Tassilo', 'Ceccarello, Erica', 'Allweiss, Lena', 'Lütgehetmann, Marc', 'Bertoletti, Antonio', 'Dandri, Maura']",,,,
,PMC,Ontology-Based Approach to Social Data Sentiment Analysis: Detection of Adolescent Depression Signals,http://dx.doi.org/10.2196/jmir.7452,PMC5547245,28739560,CC BY,"BACKGROUND: Social networking services (SNSs) contain abundant information about the feelings, thoughts, interests, and patterns of behavior of adolescents that can be obtained by analyzing SNS postings. An ontology that expresses the shared concepts and their relationships in a specific field could be used as a semantic framework for social media data analytics. OBJECTIVE: The aim of this study was to refine an adolescent depression ontology and terminology as a framework for analyzing social media data and to evaluate description logics between classes and the applicability of this ontology to sentiment analysis. METHODS: The domain and scope of the ontology were defined using competency questions. The concepts constituting the ontology and terminology were collected from clinical practice guidelines, the literature, and social media postings on adolescent depression. Class concepts, their hierarchy, and the relationships among class concepts were defined. An internal structure of the ontology was designed using the entity-attribute-value (EAV) triplet data model, and superclasses of the ontology were aligned with the upper ontology. Description logics between classes were evaluated by mapping concepts extracted from the answers to frequently asked questions (FAQs) onto the ontology concepts derived from description logic queries. The applicability of the ontology was validated by examining the representability of 1358 sentiment phrases using the ontology EAV model and conducting sentiment analyses of social media data using ontology class concepts. RESULTS: We developed an adolescent depression ontology that comprised 443 classes and 60 relationships among the classes; the terminology comprised 1682 synonyms of the 443 classes. In the description logics test, no error in relationships between classes was found, and about 89% (55/62) of the concepts cited in the answers to FAQs mapped onto the ontology class. Regarding applicability, the EAV triplet models of the ontology class represented about 91.4% of the sentiment phrases included in the sentiment dictionary. In the sentiment analyses, “academic stresses” and “suicide” contributed negatively to the sentiment of adolescent depression. CONCLUSIONS: The ontology and terminology developed in this study provide a semantic foundation for analyzing social media data on adolescent depression. To be useful in social media data analysis, the ontology, especially the terminology, needs to be updated constantly to reflect rapidly changing terms used by adolescents in social media postings. In addition, more attributes and value sets reflecting depression-related sentiments should be added to the ontology.",2017 Jul 24,"['Jung, Hyesil', 'Park, Hyeoun-Ae', 'Song, Tae-Min']",J Med Internet Res,,,
,PMC,Human Bocavirus Capsid Messenger RNA Detection in Children With Pneumonia,http://dx.doi.org/10.1093/infdis/jix352,PMC5853397,,,"BACKGROUND: The role of human bocavirus (HBoV) in respiratory illness is uncertain. HBoV genomic DNA is frequently detected in both ill and healthy children. We hypothesized that spliced viral capsid messenger RNA (mRNA) produced during active replication might be a better marker for acute infection. METHODS: As part of the Etiology of Pneumonia in the Community (EPIC) study, children aged <18 years who were hospitalized with community-acquired pneumonia (CAP) and children asymptomatic at the time of elective outpatient surgery (controls) were enrolled. Nasopharyngeal/oropharyngeal specimens were tested for HBoV mRNA and genomic DNA by quantitative polymerase chain reaction. RESULTS: HBoV DNA was detected in 10.4% of 1295 patients with CAP and 7.5% of 721 controls (odds ratio [OR], 1.4 [95% confidence interval {CI}, 1.0–2.0]); HBoV mRNA was detected in 2.1% and 0.4%, respectively (OR, 5.1 [95% CI, 1.6–26]). When adjusted for age, enrollment month, and detection of other respiratory viruses, HBoV mRNA detection (adjusted OR, 7.6 [95% CI, 1.5–38.4]) but not DNA (adjusted OR, 1.2 [95% CI, .6–2.4]) was associated with CAP. Among children with no other pathogens detected, HBoV mRNA (OR, 9.6 [95% CI, 1.9–82]) was strongly associated with CAP. CONCLUSIONS: Detection of HBoV mRNA but not DNA was associated with CAP, supporting a pathogenic role for HBoV in CAP. HBoV mRNA could be a useful target for diagnostic testing.",,"['Schlaberg, Robert', 'Ampofo, Krow', 'Tardif, Keith D', 'Stockmann, Chris', 'Simmon, Keith E', 'Hymas, Weston', 'Flygare, Steven', 'Kennedy, Brett', 'Blaschke, Anne', 'Eilbeck, Karen', 'Yandell, Mark', 'McCullers, Jon A', 'Williams, Derek J', 'Edwards, Kathryn', 'Arnold, Sandra R', 'Bramley, Anna', 'Jain, Seema', 'Pavia, Andrew T']",,,,
,PMC,The θ-defensin retrocyclin 101 inhibits TLR4- and TLR2-dependent signaling and protects mice against influenza infection,http://dx.doi.org/10.1189/jlb.2A1215-567RR,PMC5597516,,,"Despite widespread use of annual influenza vaccines, seasonal influenza-associated deaths number in the thousands each year, in part because of exacerbating bacterial superinfections. Therefore, discovering additional therapeutic options would be a valuable aid to public health. Recently, TLR4 inhibition has emerged as a possible mechanism for protection against influenza-associated lethality and acute lung injury. Based on recent data showing that rhesus macaque θ-defensins could inhibit TLR4-dependent gene expression, we tested the hypothesis that a novel θ-defensin, retrocyclin (RC)-101, could disrupt TLR4-dependent signaling and protect against viral infection. In this study, RC-101, a variant of the humanized θ-defensin RC-1, blocked TLR4-mediated gene expression in mouse and human macrophages in response to LPS, targeting both MyD88- and TRIF-dependent pathways. In a cell-free assay, RC-101 neutralized the biologic activity of LPS at doses ranging from 0.5 to 50 EU/ml, consistent with data showing that RC-101 binds biotinylated LPS. The action of RC-101 was not limited to the TLR4 pathway because RC-101 treatment of macrophages also inhibited gene expression in response to a TLR2 agonist, Pam3CSK4, but failed to bind that biotinylated agonist. Mouse macrophages infected in vitro with mouse-adapted A/PR/8/34 influenza A virus (PR8) also produced lower levels of proinflammatory cytokine gene products in a TLR4-independent fashion when treated with RC-101. Finally, RC-101 decreased both the lethality and clinical severity associated with PR8 infection in mice. Cumulatively, our data demonstrate that RC-101 exhibits therapeutic potential for the mitigation of influenza-related morbidity and mortality, potentially acting through TLR-dependent and TLR-independent mechanisms.",,"['Prantner, Daniel', 'Shirey, Kari Ann', 'Lai, Wendy', 'Lu, Wuyuan', 'Cole, Alexander M.', 'Vogel, Stefanie N.', 'Garzino-Demo, Alfredo']",,,,
,PMC,Evaluation of purified recombinant spike fragments for assessment of the presence of serum neutralizing antibodies against a variant strain of porcine epidemic diarrhea virus,http://dx.doi.org/10.1007/s12250-017-3969-8,PMC6598932,,,"Since 2010, variant strains of porcine epidemic diarrhea virus (PEDV) have caused disasters in the pork industry. The spike (S) protein, as the major immunity-eliciting antigen, has previously been used for serological testing and has been found to correlate significantly with the results of the serum neutralization (SN) test. However, further evaluation of this method is needed as new epidemic strains of PEDV emerge. Hence, the main objective of this study was to assess sow sera and determine the correlation between enzyme-linked immunosorbent assay (ELISA) results (involving a newly isolated GDS01 virus-based ELISA and ELISAs based on seven recombinant fragments comprising overlapping S1 and partial S2 sequences) and SN titers. Furthermore, we determined the reliability of the ELISAs based on receiver operating characteristics (ROC) curve analyses. For the most promising ELISA, i.e., the SP4 ELISA, the correlation coefficient (r) and the area under curve (AUC) were determined to be 0.6113 and 0.8538, respectively. In addition, we analyzed the homology of the SP4 sequences obtained from different strains (including vaccine strains) and found that various strains showed a high degree of homology in this region. Thus, we conclude that SP4 is a promising serological testing protein for use in the field. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s12250-017-3969-8 and is accessible for authorized users.",,"['Hao, Jianwei', 'Zhang, Yun', 'Fang, Shengkun', 'Wen, Zhifen', 'Zhang, Xiangbin', 'Xue, Chunyi', 'Cao, Yongchang']",,,,
,PMC,Suppressive effect of dengue virus envelope protein domain III on megakaryopoiesis,http://dx.doi.org/10.1080/21505594.2017.1343769,PMC5810469,,,"Dengue virus (DENV) infection can cause severe, life-threatening events, and no specific treatments of DENV infection are currently approved. Although thrombocytopenia is frequently observed in dengue patients, its pathogenesis is still not fully understood. Previous studies have suggested that DENV-induced thrombocytopenia occurs through viral-replication-mediated megakaryopoiesis inhibition in the bone marrow; however, the exact mechanism for megakaryopoiesis suppression remains elusive. In this study, a reductionist approach was applied, in which C57B/6J mice were inoculated with recombinant DENV-envelope protein domain III (DENV-EIII) instead of the full viral particle. Our results demonstrated that DENV-EIII-suppressed megakaryopoiesis is similar to those observed with DENV infection. Furthermore, in agreement with our in vivo analyses, DENV-EIII sufficiently suppressed the megakaryopoiesis of progenitor cells from murine bone marrow and human cord blood in vitro. Additional analyses suggested that autophagy impairment and apoptosis are involved in DENV-EIII-mediated suppression of megakaryopoiesis. These data suggest that, even without viral replication, the binding of DENV-EIII to the cell surface is sufficient to suppress megakaryopoiesis.",,"['Lin, Guan-Ling', 'Chang, Hsin-Hou', 'Lien, Te-Sheng', 'Chen, Po-Kong', 'Chan, Hao', 'Su, Mei-Tzu', 'Liao, Chi-Yuan', 'Sun, Der-Shan']",,,,
,PMC,The Bordetella Bps Polysaccharide Is Required for Biofilm Formation and Enhances Survival in the Lower Respiratory Tract of Swine,http://dx.doi.org/10.1128/IAI.00261-17,PMC5520422,,,"Bordetella bronchiseptica is pervasive in swine populations and plays multiple roles in respiratory disease. Additionally, B. bronchiseptica is capable of establishing long-term or chronic infections in swine. Bacterial biofilms are increasingly recognized as important contributors to chronic bacterial infections. Recently the polysaccharide locus bpsABCD has been demonstrated to serve a critical role in the development of mature biofilms formed by the sequenced laboratory strain of B. bronchiseptica. We hypothesized that swine isolates would also have the ability to form mature biofilms and the bpsABCD locus would serve a key role in this process. A mutant containing an in-frame deletion of the bpsABCD structural genes was constructed in a wild-type swine isolate and found to be negative for poly-N-acetylglucosamine (PNAG)-like material by immunoblot assay. Further, the bpsABCD locus was found to be required for the development and maintenance of the three-dimensional structures under continuous-flow conditions. To investigate the contribution of the bpsABCD locus to the pathogenesis of B. bronchiseptica in swine, the KM22Δbps mutant was compared to the wild-type swine isolate for the ability to colonize and cause disease in pigs. The bpsABCD locus was found to not be required for persistence in the upper respiratory tract of swine. Additionally, the bpsABCD locus did not affect the development of anti-Bordetella humoral immunity, did not contribute to disease severity, and did not mediate protection from complement-mediated killing. However, the bpsABCD locus was found to enhance survival in the lower respiratory tract of swine.",,"['Nicholson, Tracy L.', 'Brockmeier, Susan L.', 'Sukumar, Neelima', 'Paharik, Alexandra E.', 'Lister, Jessica L.', 'Horswill, Alexander R.', 'Kehrli, Marcus E.', 'Loving, Crystal L.', 'Shore, Sarah M.', 'Deora, Rajendar']",,,,
,PMC,A Novel Strategy for Bitter Taste Masking of Gankeshuangqing Dispersible Tablets Based on Particle Coating Technology,http://dx.doi.org/10.4103/pm.pm_240_16,PMC5551356,28839363,CC BY-NC-SA,"BACKGROUND: Currently, acute upper respiratory tract infections (AURTIs) are increasingly becoming a significant health burden. Gankeshuangqing dispersible tablets (GKSQDT) which have a good effect on treating AURTIs. GKSQDT is composed of baicalin and andrographolide. However, its severe bitterness limits application of patients. Due to the addition of plentiful accessories, common masking methods are unsuitable for GKSQDT. It is thus necessary to develop a new masking method. MATERIALS AND METHODS: The Previous study showed that baicalin was less bitter than andrographolide. Thus, particle coating technology was adapted to prepare composite particles that baicalin coated on the surface of andrographolide to decrease bitterness. Initially, particle size of baicalin and coating time of composite was investigated to prepare composite. Then, scanning electron microscopy, wettability, and infrared (IR) spectrogram were used to characterize the microstructure of composite. Furthermore, electronic tongue test, animal preference experiment, and human sensory test were applied to evaluate the masking effect. RESULTS: To produce composite, baicalin should be ground in vibromill for 6 min. Then, andrographolide fine powder was added to grind together for 6 min. Contact angle of composite was smaller than mixture, and more similar to baicalin. Other physical characterization including microstructure, wettability, and IR also suggested that andrographolide was successfully coated by baicalin superfine. Furthermore, taste-masking test indicated taste-masked tablets was less bitter than original tablets. CONCLUSION: The study indicated that particle coating technology can be used for taste masking of GKSQDT without adding other substance. Moreover, it provides a new strategy of taste masking for national medicine. SUMMARY: A new strategy to mask bitterness without adding any other substance based on coating technology was provided. The masking effect was confirmed by electronic tongue test, animal preference experiment and human sensory test. Abbreviations used: AURTIs: Acute Upper Respiratory Tract Infections; GSQDT: Gankeshuangqing Dispersible Tablets; IR: Infrared Spectrogram; LHPC: Low-substituted Hydroxypropyl Cellulose; CAs: Contact Angles; FTIR: Fourier Transform Infrared Spectra.",2017 Jul 19 Jul-Sep,"['Han, Xue', 'Zhang, Ding-Kun', 'Zhang, Fang', 'Lin, Jun-Zhi', 'Jiang, Hong', 'Lan, Yang', 'Xiong, Xi', 'Han, Li', 'Yang, Ming', 'Fu, Chao-Mei']",Pharmacogn Mag,,,
,PMC,Stress hormones predict a host superspreader phenotype in the West Nile virus system,http://dx.doi.org/10.1098/rspb.2017.1090,PMC5543230,,,"Glucocorticoid stress hormones, such as corticosterone (CORT), have profound effects on the behaviour and physiology of organisms, and thus have the potential to alter host competence and the contributions of individuals to population- and community-level pathogen dynamics. For example, CORT could alter the rate of contacts among hosts, pathogens and vectors through its widespread effects on host metabolism and activity levels. CORT could also affect the intensity and duration of pathogen shedding and risk of host mortality during infection. We experimentally manipulated songbird CORT, asking how CORT affected behavioural and physiological responses to a standardized West Nile virus (WNV) challenge. Although all birds became infected after exposure to the virus, only birds with elevated CORT had viral loads at or above the infectious threshold. Moreover, though the rate of mortality was faster in birds with elevated CORT compared with controls, most hosts with elevated CORT survived past the day of peak infectiousness. CORT concentrations just prior to inoculation with WNV and anti-inflammatory cytokine concentrations following viral exposure were predictive of individual duration of infectiousness and the ability to maintain physical performance during infection (i.e. tolerance), revealing putative biomarkers of competence. Collectively, our results suggest that glucocorticoid stress hormones could directly and indirectly mediate the spread of pathogens.",,"['Gervasi, Stephanie S.', 'Burgan, Sarah C.', 'Hofmeister, Erik', 'Unnasch, Thomas R.', 'Martin, Lynn B.']",,,,
,PMC,NS2A comprises a putative viroporin of Dengue virus 2,http://dx.doi.org/10.1080/21505594.2017.1356540,PMC5711424,,,,,"['Shrivastava, Gaurav', 'García-Cordero, Julio', 'León-Juárez, Moisés', 'Oza, Goldie', 'Tapia-Ramírez, Jose', 'Villegas-Sepulveda, Nicolas', 'Cedillo-Barrón, Leticia']",,,,
,PMC,Pentraxin-3 Modulates LPS-induced Inflammatory Response and Attenuates Liver Injury,http://dx.doi.org/10.1002/hep.29215,PMC5570620,,,"Acute-on-chronic liver injury is characterized by an important inflammatory response frequently associated with endotoxemia. In this context, acute phase proteins such as Pentraxin-3 (PTX3) are released, however, little is known about their role in chronic liver disease. The aim of this study was to elucidate the role of PTX3 in liver injury. Role of PTX3 was evaluated in cultured human cells, liver tissue slices and mice with acute-on-chronic liver injury. PTX3 expression was assessed in tissue and serum samples from 54 patients with alcoholic hepatitis (AH). PTX3 expression was up-regulated in animal models of liver injury and strongly induced by lipopolysaccharide (LPS). Liver cell fractionation showed that macrophages and activated hepatic stellate cells (HSC) were the main cell types expressing PTX3 in liver injury. Ex vivo, and in vivo studies showed that PTX3 treatment attenuated LPS-induced liver injury, inflammation and cell recruitment. Mechanistically, PTX3 mediated HSC wound-healing response. Moreover, PTX3 modulated LPS-induced inflammation in human primary liver macrophages and peripheral monocytes by enhancing a TRIF-dependent response and favoring a macrophage IL-10-like phenotype. Additionally, hepatic and plasma PTX3 levels were up-regulated in patients with AH, a prototypic acute-on-chronic condition and its expression correlated with disease severity scores, endotoxemia, infections and short-term mortality. Thus, suggesting that expression of PTX3 found in patients could be a counterregulatory response to injury. CONCLUSION: Experimental and human evidences suggest that in addition to being a potential biomarker for AH, PTX3 participates in wound-healing response and attenuates LPS-induced liver injury and inflammation. Therefore, administration of PTX3 could be a promising therapeutic strategy in acute-on-chronic conditions, particularly those associated with endotoxemia.",,"['Perea, Luis', 'Coll, Mar', 'Sanjurjo, Lucia', 'Blaya, Delia', 'Taghdouini, Adil El', 'Rodrigo-Torres, Daniel', 'Altamirano, José', 'Graupera, Isabel', 'Aguilar-Bravo, Beatriz', 'Llopis, Marta', 'Vallverdú, Julia', 'Caballeria, Joan', 'van Grunsven, Leo A.', 'Sarrias, Maria-Rosa', 'Ginès, Pere', 'Sancho-Bru, Pau']",,,,
,PMC,Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children,http://dx.doi.org/10.1001/jama.2017.8708,PMC5817430,,,"IMPORTANCE: Epidemiological studies support a link between low 25-hydroxyvitamin D levels and a higher risk of viral upper respiratory tract infections. However, whether winter supplementation of vitamin D reduces the risk among children is unknown. OBJECTIVE: To determine whether high-dose vs standard-dose vitamin D supplementation reduces the incidence of wintertime upper respiratory tract infections in young children. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial was conducted during the winter months between September 13, 2011, and June 30, 2015, among children aged 1 through 5 years enrolled in TARGet Kids!, a multisite primary care practice–based research network in Toronto, Ontario, Canada. INTERVENTIONS: Three hundred forty-nine participants were randomized to receive 2000 IU/d of vitamin D oral supplementation (high-dose group) vs 354 participants who were randomized to receive 400 IU/d (standard-dose group) for a minimum of 4 months between September and May. MAIN OUTCOME MEASURES: The primary outcome was the number of laboratory-confirmed viral upper respiratory tract infections based on parent-collected nasal swabs over the winter months. Secondary outcomes included the number of influenza infections, noninfluenza infections, parent-reported upper respiratory tract illnesses, time to first upper respiratory tract infection, and serum 25-hydroxyvitamin D levels at study termination. RESULTS: Among 703 participants who were randomized (mean age, 2.7 years, 57.7% boys), 699 (99.4%) completed the trial. The mean number of laboratory-confirmed upper respiratory tract infections per child was 1.05 (95% CI, 0.91-1.19) for the high-dose group and 1.03 (95% CI, 0.90-1.16) for the standard-dose group, for a between-group difference of 0.02 (95% CI, −0.17 to 0.21) per child. There was no statistically significant difference in number of laboratory-confirmed infections between groups (incidence rate ratio [RR], 0.97; 95% CI, 0.80-1.16). There was also no significant difference in the median time to the first laboratory-confirmed infection: 3.95 months (95% CI, 3.02-5.95 months) for the high-dose group vs 3.29 months (95% CI, 2.66-4.14 months) for the standard-dose group, or number of parent-reported upper respiratory tract illnesses between groups (625 for high-dose vs 600 for standard-dose groups, incidence RR, 1.01; 95% CI, 0.88-1.16). At study termination, serum 25-hydroxyvitamin D levels were 48.7 ng/mL (95% CI, 46.9-50.5 ng/mL) in the high-dose group and 36.8 ng/mL (95% CI, 35.4-38.2 ng/mL) in the standard-dose group. CONCLUSIONS AND RELEVANCE: Among healthy children aged 1 to 5 years, daily administration of 2000 IU compared with 400 IU of vitamin D supplementation did not reduce overall wintertime upper respiratory tract infections. These findings do not support the routine use of high-dose vitamin D supplementation in children for the prevention of viral upper respiratory tract infections. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01419262",,"['Aglipay, Mary', 'Birken, Catherine S.', 'Parkin, Patricia C.', 'Loeb, Mark B.', 'Thorpe, Kevin', 'Chen, Yang', 'Laupacis, Andreas', 'Mamdani, Muhammad', 'Macarthur, Colin', 'Hoch, Jeffrey S.', 'Mazzulli, Tony', 'Maguire, Jonathon L.']",,,,
,PMC,Amplicon competition enables end-point quantitation of nucleic acids following isothermal amplification,http://dx.doi.org/10.1002/cbic.201700317,PMC5890436,,,"It is inherently difficult to quantitate nucleic acid analytes with most isothermal amplification assays. We have now developed loop-mediated isothermal amplification (LAMP) reactions in which competition between defined numbers of ‘false’ and ‘true’ amplicons leads to order of magnitude quantitation via a single end-point determination. These thresholded LAMP reactions were successfully used to directly and quantitatively estimate the numbers of nucleic acids in complex biospecimens, including directly from cells and in sewage, with the values obtained closely correlating with qPCR quantitations. Thresholded LAMP reactions are amenable to endpoint readout via cell phone, unlike other methods that require continuous monitoring, and should therefore prove extremely useful in developing one-pot reactions for point-of-care diagnostics determinations without any sophisticated material or informatics infrastructure.",,"['Jiang, Yu Sherry', 'Stacy, Apollo', 'Whiteley, Marvin', 'Ellington, Andrew D.', 'Bhadra, Sanchita']",,,,
,PMC,SNP-mediated disruption of CTCF binding at the IFITM3 promoter is associated with severe influenza risk in humans,http://dx.doi.org/10.1038/nm.4370,PMC5702558,,,"Previous studies reported associations of IFITM3 SNP rs12252 with severe influenza, but evidence of association and the mechanism of risk remains controversial. We prioritized SNPs in IFITM3 based on putative biological function and identified rs34481144 in the 5′ UTR. We found evidence of a novel association of rs34481144 with severe influenza in three influenza-infected cohorts characterized by different levels of influenza illness severity. We determined the role of rs34481144 as an expression quantitative trait loci (eQTL) for IFITM3, with the risk allele associated with lower mRNA expression. The risk allele was found to have decreased IRF3 binding and increased CTCF binding in promoter-binding assays, and risk allele carriage diminished transcriptional correlations among neighboring genes, indicative of CTCF boundary activity. Furthermore, the risk allele disrupts a CpG site that undergoes differential methylation in CD8 T-cell subsets. Carriers of the risk allele had reduced CD8 T-cells in their airways during natural influenza infection, consistent with IFITM3 promoting airway CD8 T-cell accumulation, indicating that a critical function for IFITM3 may be to promote immune cell persistence at mucosal sites. Our study identifies a new regulator of IFITM3 expression that associates with CD8 T-cell levels in the airways and a spectrum of clinical outcomes.",,"['Allen, E. Kaitlynn', 'Randolph, Adrienne G.', 'Bhangale, Tushar', 'Dogra, Pranay', 'Ohlson, Maikke', 'Oshansky, Christine M.', 'Zamora, Anthony E.', 'Shannon, John P.', 'Finkelstein, David', 'Dressen, Amy', 'DeVincenzo, John', 'Caniza, Miguela', 'Youngblood, Ben', 'Rosenberger, Carrie M.', 'Thomas, Paul G.']",,,,
,PMC,Severe viral respiratory infections in children with IFIH1 loss-of-function mutations,http://dx.doi.org/10.1073/pnas.1704259114,PMC5547624,,,"Viral respiratory infections are usually mild and self-limiting; still they exceptionally result in life-threatening infections in previously healthy children. To investigate a potential genetic cause, we recruited 120 previously healthy children requiring support in intensive care because of a severe illness caused by a respiratory virus. Using exome and transcriptome sequencing, we identified and characterized three rare loss-of-function variants in IFIH1, which encodes an RIG-I-like receptor involved in the sensing of viral RNA. Functional testing of the variants IFIH1 alleles demonstrated that the resulting proteins are unable to induce IFN-β, are intrinsically less stable than wild-type IFIH1, and lack ATPase activity. In vitro assays showed that IFIH1 effectively restricts replication of human respiratory syncytial virus and rhinoviruses. We conclude that IFIH1 deficiency causes a primary immunodeficiency manifested in extreme susceptibility to common respiratory RNA viruses.",,"['Asgari, Samira', 'Schlapbach, Luregn J.', 'Anchisi, Stéphanie', 'Hammer, Christian', 'Bartha, Istvan', 'Junier, Thomas', 'Mottet-Osman, Geneviève', 'Posfay-Barbe, Klara M.', 'Longchamp, David', 'Stocker, Martin', 'Cordey, Samuel', 'Kaiser, Laurent', 'Riedel, Thomas', 'Kenna, Tony', 'Long, Deborah', 'Schibler, Andreas', 'Telenti, Amalio', 'Tapparel, Caroline', 'McLaren, Paul J.', 'Garcin, Dominique', 'Fellay, Jacques']",,,,
,PMC,"Detection and characterization of three zoonotic viruses in wild rodents and shrews from Shenzhen city, China",http://dx.doi.org/10.1007/s12250-017-3973-z,PMC6598888,,,"Diverse species of rodents and shrews, which are abundant worldwide, harbor a variety of viruses; some of these are closely related to human viruses and possess zoonotic potential. Previously studies have demonstrated that the mammarenavirus and hantavirus carried by rodents or shrews could cause diseases in human population. To determine the distribution of zoonotic viruses in Shenzhen city, the major city in southern China with a high population density, we analyzed 225 rodents (Rattus norvegicus and Rattus flavipectus) and 196 shrews (Suncus murinus) from urban and rural districts for the presence of mammarenavirus, hantavirus, and hepatitis E virus (HEV) by RT-PCR targeting the conserved regions. The infection rates for mammarenavirus, hantaviruses, and HEV in rodents and shrews were 3.56%, 6.89%, and 1.66%, respectively. Partial genome fragment analysis indicated that mammarenavirus and hantavirus strains had more than 90% and 99% nucleic acid identity with Cardamones virus and Seoul virus, respectively, which cause diseases in humans. Although the present HEV strains identified are typically found worldwide, phylogenetic analysis demonstrated a divergence of 16%. To our knowledge, the present work is the first report of the prevalence of mammarenavirus, hantaviruses, and rat HEV strains in rodents and shrews from Shenzhen city, China. Our findings highlight the zoonotic potential of rodent- and shrew-borne mammarenavirus and hantavirus, and the biodiversity of rat HEV isolates in Shenzhen city. The present work suggests that utilization of good hygiene habits is important to minimize the risk of zoonosis.",,"['Wang, Bo', 'Cai, Chun-Lin', 'Li, Bei', 'Zhang, Wei', 'Zhu, Yan', 'Chen, Wei-Hong', 'Zhuo, Fei', 'Shi, Zheng-Li', 'Yang, Xing-Lou']",,,,
,PMC,Intradermal Immunization with rAAV1 Vector Induces Robust Memory CD8(+) T Cell Responses Independently of Transgene Expression in DCs,http://dx.doi.org/10.1016/j.ymthe.2017.06.019,PMC5628776,,,"Recombinant adeno-associated viral (rAAV) vectors exhibit interesting properties as vaccine carriers for their ability to induce long-lasting antibody responses. However, rAAV-based vaccines have been suggested to trigger functionally impaired long-term memory CD8(+) T cell responses, in part due to poor dendritic cell (DC) transduction. Such results, albeit limited to intramuscular immunization, undermined the use of rAAV as vaccine vehicles against intracellular pathogens. We report here that intradermal immunization with a model rAAV2/1-based vaccine drives the development of bona fide long-term memory CD8(+) T cell responses. The intradermal route of immunization and the presence of potent major histocompatibility complex (MHC) class II responses showed synergistic effects on the overall quantity and quality of systemic long-term effector memory transgene-specific CD8(+) T cells being generated against the transgene. Of key interest, we found that the induction of memory cytotoxic T lymphocytes (CTLs) following intradermal immunization was solely dependent on the cross-presentation of skin-expressed transgene products, which appeared highly enhanced as compared to muscle-expressed transgene products. Overall our results highlight key tissue-specific differences in transgene presentation pathway requirements of importance for the design of rAAV-based T cell-inducing vaccines.",,"['Ghenassia, Alexandre', 'Gross, David-Alexandre', 'Lorain, Stéphanie', 'Tros, Fabiola', 'Urbain, Dominique', 'Benkhelifa-Ziyyat, Sofia', 'Charbit, Alain', 'Davoust, Jean', 'Chappert, Pascal']",,,,
,PMC,Application of Epstein–Barr Virus for Optimization of Immortalized B-lymphocyte Production as a Positive Control in Genetic Studies,http://dx.doi.org/10.4103/2277-9175.210659,PMC5539668,28808646,CC BY-NC-SA,"BACKGROUND: Infection of B-cells with Epstein–Barr virus (EBV) leads to more and subsequent immortalization. This is considered as the method of choice for generating lymphoblastoid cell lines (LCLs). Producing LCLs, although very useful but is very time consuming and troublesome, drives the requirement for quicker and more reliable methods for EBV-driven B-cell transformation. MATERIALS AND METHODS: After successfully production of LCLs, different parameters including temperature, serum concentration, type of culture medium, and CO(2) concentration were evaluated on EBV-transformed B-cells. In this study, we were able to produce LCLs and optimize condition. RESULTS: The best condition for generating LCLs was 37°C, 5% CO(2), 20% fasting blood sugar, and RPMI 1640. The study results were to establish a reliable method for producing LCLs that can be used to produce immortalized B-cells from almost any sources. CONCLUSION: This can help with tumorgenecity studies, as well as producing control material for rare genetic disorders and so on. The aim of this study was to determine optimized condition for reliable and reproducible LCLs from different sources.",2017 Jul 14,"['Tousizadeh, Behnaz', 'Moghim, Sharareh', 'Chaleshtori, Ahmad Reza Salehi', 'Ghanbarian, Maryam', 'Mirian, Mina', 'Salehi, Mansoor', 'Tousizadeh, Sepideh', 'Zaboli, Fatemeh']",Adv Biomed Res,,,
,PMC,Letter from the editor,http://dx.doi.org/10.1080/21645515.2017.1348825,PMC5512794,,,,,,,,,
,PMC,Role of Fly Cleaning Behavior on Carriage of Escherichia coli and Pseudomonas aeruginosa,http://dx.doi.org/10.1093/jme/tjx124,PMC5850793,,,"Flies are known to be mechanical vectors of bacterial, viral, and parasitic diseases. Although flies are known to transmit disease, the effects of cleaning behavior have not been well studied. This study quantified the cleaning effectiveness and behavior of three fly species: Sarcophaga bullata, Musca domestica L., and Drosophila virilis. Flies were transferred to plates of Escherichia coli or Pseudomonas aeruginosa and allowed to walk on the bacteria for a total of 5 min. After the flies were contaminated, they were either immediately collected to quantify bacteria or were placed onto sterile plates to clean for 5 or 10 min. After cleaning, flies were placed into tubes with 1 ml of sterile 0.85% saline and were gently shaken for 1 min to remove bacteria. A serial dilution was made and 50-µl spot titers were plated. Cleaning behavior was also monitored and scored for a period of 5 min. Results demonstrate a bacterial reduction for both bacteria on all three fly species. Sarcophaga bullata and D. virilis both showed a significant reduction of both bacteria within 10 min, whereas M. domestica only showed a significant reduction in P. aeruginosa. Cleaning behavior increased significantly in flies that were exposed to bacteria compared to flies that were not exposed to bacteria. This study is important, as it demonstrates that fly cleaning could affect mechanical transmission of disease, and additional studies should look at flies’ abilities to remove other types of microorganisms.",,"['Jacques, B J', 'Bourret, T J', 'Shaffer, J J']",,,,
,PMC,Opportunities and Challenges in Modeling Emerging Infectious Diseases,http://dx.doi.org/10.1126/science.aam8335,PMC6776075,,,"The term ‘pathogen emergence’ encompasses everything from novel viruses entering the human population to established pathogens invading new populations, to the evolution of drug resistance. Mathematical models of emergent pathogens allow forecasts of case numbers, investigation of transmission mechanisms, and evaluation of control options. Yet, there are numerous limitations and pitfalls to their use, often driven by data scarcity. Growing availability of data on pathogen genetics and human ecology, coupled with computational and methodological innovations, are amplifying the power of models to inform the public health response to emergence events. Tighter integration of infectious disease models with public health practice, and development of resources at the ready have the potential to increase the timeliness and quality of responses.",,"['Metcalf, C. Jessica E.', 'Lessler, Justin']",,,,
,PMC,Improving vaccine trials in infectious disease emergencies,http://dx.doi.org/10.1126/science.aam8334,PMC5568786,,,"Unprecedented global effort is underway to facilitate testing of countermeasures in infectious disease emergencies. Better understanding of the various options for trial design, as well as preliminary global agreement on the most suitable designs for the various scenarios, are needed now—in advance of outbreaks. What would enhance, then, the speed, validity, and ethics of clinical studies of such countermeasures? Focusing on studies of vaccine efficacy and effectiveness in emergencies, we highlight three needs: for formal randomized trials—even in most emergencies; for individually-randomized trials—even in many emergencies; and for six areas of innovation in trial methodology. These needs should inform current updates of protocols and roadmaps.",,"['Lipsitch, Marc', 'Eyal, Nir']",,,,
,PMC,The Orchestra of Reovirus Cell Entry,http://dx.doi.org/10.1007/s40588-017-0067-5,PMC6897391,,,"PURPOSE OF REVIEW: the ability of viruses to infect host cells is dependent on several factors including the availability of cell-surface receptors, antiviral state of cells, and presence of host factors needed for viral replication. Here we review findings from in vitro and in vivo studies using mammalian orthoreovirus (reovirus) that have identified an intricate group of molecules and mechanisms used by the virus to attach and enter cells. RECENT FINDINGS: recent findings provide an improved mechanistic understanding of reovirus cell entry. Of special note is the identification of a cellular mediator of cell entry in neuronal and non-neuronal cells, the effect of cell entry on the outcome of infection and cytopathic effects on the host cell, and an improved understanding of the components that promote viral penetration of cellular membranes. SUMMARY: a mechanistic understanding of the interplay between host and viral factors has enhanced our view of how viruses usurp cellular processes during infection.",,"Mainou, Bernardo A.",,,,
,PMC,Development of an Aryloxazole Class of Hepatitis C Virus Inhibitors Targeting the Entry Stage of the Viral Replication Cycle,http://dx.doi.org/10.1021/acs.jmedchem.7b00561,PMC6015499,,,"Reliance on hepatitis C virus (HCV) replicon systems and protein-based screening assays has led to treatments that target HCV viral replication proteins. The model does not encompass other viral replication cycle steps such as entry, processing, assembly and secretion, or viral host factors. We previously applied a phenotypic high-throughput screening platform based on an infectious HCV system and discovered an aryloxazole-based anti-HCV hit. Structure– activity relationship studies revealed several compounds exhibiting EC(50) values below 100 nM. Lead compounds showed inhibition of the HCV pseudoparticle entry, suggesting a different mode of action from existing HCV drugs. Hit 7a and lead 7ii both showed synergistic effects in combination with existing HCV drugs. In vivo pharmacokinetics studies of 7ii showed high liver distribution and long half-life without obvious hepatotoxicity. The lead compounds are promising as preclinical candidates for the treatment of HCV infection and as molecular probes to study HCV pathogenesis.",,"['He, Shanshan', 'Li, Kelin', 'Lin, Billy', 'Hu, Zongyi', 'Xiao, Jingbo', 'Hu, Xin', 'Wang, Amy Q.', 'Xu, Xin', 'Ferrer, Marc', 'Southall, Noel', 'Zheng, Wei', 'Aubé, Jeffrey', 'Schoenen, Frank J.', 'Marugan, Juan J.', 'Liang, T. Jake', 'Frankowski, Kevin J.']",,,,
,PMC,Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase Fidelity,http://dx.doi.org/10.1128/JVI.00081-17,PMC5651715,,,"Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp) (3D(pol)) catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of proofreading activity allow FMDV to rapidly mutate and adapt to dynamic environments. In this study, we used the structure of FMDV 3D(pol) in combination with previously reported results from similar picornaviral polymerases to design point mutations that would alter replication fidelity. In particular, we targeted Trp237 within conserved polymerase motif A because of the low reversion potential inherent in the single UGG codon. Using biochemical and genetic tools, we show that the replacement of tryptophan 237 with phenylalanine imparts higher fidelity, but replacements with isoleucine and leucine resulted in lower-fidelity phenotypes. Viruses containing these W237 substitutions show in vitro growth kinetics and plaque morphologies similar to those of the wild-type (WT) A(24) Cruzeiro strain in BHK cells, and both high- and low-fidelity variants retained fitness during coinfection with the wild-type virus. The higher-fidelity W237F (W237F(HF)) mutant virus was more resistant to the mutagenic nucleoside analogs ribavirin and 5-fluorouracil than the WT virus, whereas the lower-fidelity W237I (W237I(LF)) and W237L(LF) mutant viruses exhibited lower ribavirin resistance. Interestingly, the variant viruses showed heterogeneous and slightly delayed growth kinetics in primary porcine kidney cells, and they were significantly attenuated in mouse infection experiments. These data demonstrate, for a single virus, that either increased or decreased RdRp fidelity attenuates virus growth in animals, which is a desirable feature for the development of safer and genetically more stable vaccine candidates. IMPORTANCE Foot-and-mouth disease (FMD) is the most devastating disease affecting livestock worldwide. Here, using structural and biochemical analyses, we have identified FMDV 3D(pol) mutations that affect polymerase fidelity. Recombinant FMDVs containing substitutions at 3D(pol) tryptophan residue 237 were genetically stable and displayed plaque phenotypes and growth kinetics similar to those of the wild-type virus in cell culture. We further demonstrate that viruses harboring either a W237F(HF) substitution or W237I(LF) and W237L(LF) mutations were highly attenuated in animals. Our study shows that obtaining 3D(pol) fidelity variants by protein engineering based on polymerase structure and function could be exploited for the development of attenuated FMDV vaccine candidates that are safer and more stable than strains obtained by selective pressure via mutagenic nucleotides or adaptation approaches.",,"['Rai, Devendra K.', 'Diaz-San Segundo, Fayna', 'Campagnola, Grace', 'Keith, Anna', 'Schafer, Elizabeth A.', 'Kloc, Anna', 'de los Santos, Teresa', 'Peersen, Olve', 'Rieder, Elizabeth']",,,,
,PMC,Crimean-Congo Hemorrhagic Fever Virus Nucleocapsid Protein Augments mRNA Translation,http://dx.doi.org/10.1128/JVI.00636-17,PMC5512247,,,"Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne Nairovirus of the Bunyaviridae family, causing severe illness with high mortality rates in humans. Here, we demonstrate that CCHFV nucleocapsid protein (CCHFV-NP) augments mRNA translation. CCHFV-NP binds to the viral mRNA 5′ untranslated region (UTR) with high affinity. It facilitates the translation of reporter mRNA both in vivo and in vitro with the assistance of the viral mRNA 5′ UTR. CCHFV-NP equally favors the translation of both capped and uncapped mRNAs, demonstrating the independence of this translation strategy on the 5′ cap. Unlike the canonical host translation machinery, inhibition of eIF4F complex, an amalgam of three initiation factors, eIF4A, eIF4G, and eIF4E, by the chemical inhibitor 4E1RCat did not impact the CCHFV-NP-mediated translation mechanism. However, the proteolytic degradation of eIF4G alone by the human rhinovirus 2A protease abrogated this translation strategy. Our results demonstrate that eIF4F complex formation is not required but eIF4G plays a critical role in this translation mechanism. Our results suggest that CCHFV has adopted a unique translation mechanism to facilitate the translation of viral mRNAs in the host cell cytoplasm where cellular transcripts are competing for the same translation apparatus. IMPORTANCE Crimean-Congo hemorrhagic fever, a highly contagious viral disease endemic to more than 30 countries, has limited treatment options. Our results demonstrate that NP favors the translation of a reporter mRNA harboring the viral mRNA 5′ UTR. It is highly likely that CCHFV uses an NP-mediated translation strategy for the rapid synthesis of viral proteins during the course of infection. Shutdown of this translation mechanism might selectively impact viral protein synthesis, suggesting that an NP-mediated translation strategy is a target for therapeutic intervention against this viral disease.",,"['Jeeva, Subbiah', 'Cheng, Erdong', 'Ganaie, Safder S.', 'Mir, Mohammad A.']",,,,
,PMC,A Map of the Arenavirus Nucleoprotein-Host Protein Interactome Reveals that Junín Virus Selectively Impairs the Antiviral Activity of Double-Stranded RNA-Activated Protein Kinase (PKR),http://dx.doi.org/10.1128/JVI.00763-17,PMC5512243,,,"Arenaviruses are enveloped negative-strand RNA viruses that cause significant human disease. These viruses encode only four proteins to accomplish the viral life cycle, so each arenavirus protein likely plays unappreciated accessory roles during infection. Here we used immunoprecipitation and mass spectrometry to identify human proteins that interact with the nucleoproteins (NPs) of the Old World arenavirus lymphocytic choriomeningitis virus (LCMV) and the New World arenavirus Junín virus (JUNV) strain Candid #1. Bioinformatic analysis of the identified protein partners of NP revealed that host translation appears to be a key biological process engaged during infection. In particular, NP associates with the double-stranded RNA (dsRNA)-activated protein kinase (PKR), a well-characterized antiviral protein that inhibits cap-dependent protein translation initiation via phosphorylation of eIF2α. JUNV infection leads to increased expression of PKR as well as its redistribution to viral replication and transcription factories. Further, phosphorylation of PKR, which is a prerequisite for its ability to phosphorylate eIF2α, is readily induced by JUNV. However, JUNV prevents this pool of activated PKR from phosphorylating eIF2α, even following exposure to the synthetic dsRNA poly(I·C), a potent PKR agonist. This blockade of PKR function is highly specific, as LCMV is unable to similarly inhibit eIF2α phosphorylation. JUNV's ability to antagonize the antiviral activity of PKR appears to be complete, as silencing of PKR expression has no impact on viral propagation. In summary, we provide a detailed map of the host machinery engaged by arenavirus NPs and identify an antiviral pathway that is subverted by JUNV. IMPORTANCE Arenaviruses are important human pathogens for which FDA-approved vaccines do not exist and effective antiviral therapeutics are needed. Design of antiviral treatment options and elucidation of the mechanistic basis of disease pathogenesis will depend on an increased basic understanding of these viruses and, in particular, their interactions with the host cell machinery. Identifying host proteins critical for the viral life cycle and/or pathogenesis represents a useful strategy to uncover new drug targets. This study reveals, for the first time, the extensive human protein interactome of arenavirus nucleoproteins and uncovers a potent antiviral host protein that is neutralized during Junín virus infection. In so doing, it shows further insight into the interplay between the virus and the host innate immune response and provides an important data set for the field.",,"['King, Benjamin R.', 'Hershkowitz, Dylan', 'Eisenhauer, Philip L.', 'Weir, Marion E.', 'Ziegler, Christopher M.', 'Russo, Joanne', 'Bruce, Emily A.', 'Ballif, Bryan A.', 'Botten, Jason']",,,,
,PMC,Zbtb7a induction in alveolar macrophages is obligatory in anti-human leukocyte antigen-mediated lung allograft rejection,http://dx.doi.org/10.1126/scitranslmed.aal1243,PMC5846477,,,"Chronic rejection (CR) significantly limits long-term success of solid organ transplantation. De novo antibodies to mismatched donor human leukocyte antigen (DSA) following human lung transplantation (LTx) predispose lung grafts to CR. We sought to delineate mechanisms and mediators of DSA pathogenesis, and to define early inflammatory events that trigger CR in LTx recipients and obliterative airway disease (a correlate of human CR) in a murine model. Induction of transcription factor Zn finger BTB domain containing protein 7A (Zbtb7a) was an early response critical in DSA-induced CR. A cohort of human LTx recipients that developed DSA and CR demonstrated greater Zbtb7a expression long before clinical diagnosis of CR compared to non-rejecting LTx recipients with stable pulmonary function. Expression of DSA-induced Zbtb7a was restricted to alveolar macrophage (AM), and selective disruption of Zbtb7a in AM resulted in less bronchiolar occlusion, low immune responses to lung-restricted self-antigens, and high protection from CR. Additionally, in allogeneic cell transfer protocol, antigen presentation by AM was Zbtb7a-dependent, whereas AMs deficient in Zbtb7a failed to induce antibody and T cell responses. Collectively, we demonstrate that AM plays an essential role in antibody-induced pathogenesis of CR by regulating early inflammation and lung-restricted humoral and cellular autoimmunity. The AM-centric responses were Zbtb7a-dependent, whereas Zbtb7a-sufficient AM (not Zbtb7a-deficient AM) initiated and/or amplified DSA and DSA-induced effector functions.",,"['Nayak, Deepak K.', 'Zhou, Fangyu', 'Xu, Min', 'Huang, Jing', 'Tsuji, Moriya', 'Yu, Jinsheng', 'Hachem, Ramsey', 'Gelman, Andrew E.', 'Bremner, Ross M.', 'Smith, Michael A.', 'Mohanakumar, Thalachallour']",,,,
,PMC,HIGHLIGHTS FROM THE 2016 NORTH AMERICAN CYSTIC FIBROSIS CONFERENCE,http://dx.doi.org/10.1002/ppul.23707,PMC5963883,,,"The 30th annual North American Cystic Fibrosis Conference (NACFC) was held in Orlando, FL, on Oct. 27-29, 2016. Abstracts were published in a supplement to Pediatric Pulmonology.(1) This review summarizes several major topic areas addressed at the conference: the pathophysiology of cystic fibrosis (CF) lung disease,clinical trials, clinical management issues, and quality improvement. We sought to provide an overview of emerging concepts in several areas of CF research and care, rather than a comprehensive review of the conference. Citations from the conference are by first author and abstract number or symposium number, as designated in the supplement.",,"['Zemanick, Edith T.', 'Daines, Cori L.', 'Dellon, Elisabeth P.', 'Esthe, Charles R.', 'BreAnna, Kinghorn', 'Ong, Thida', 'Muhlebach, Marianne S.']",,,,
,PMC,The Evolution of BioSense: Lessons Learned and Future Directions,http://dx.doi.org/10.1177/0033354917706954,PMC5676506,,,"The BioSense program was launched in 2003 with the aim of establishing a nationwide integrated public health surveillance system for early detection and assessment of potential bioterrorism-related illness. The program has matured over the years from an initial Centers for Disease Control and Prevention–centric program to one focused on building syndromic surveillance capacity at the state and local level. The uses of syndromic surveillance have also evolved from an early focus on alerts for bioterrorism-related illness to situational awareness and response, to various hazardous events and disease outbreaks. Future development of BioSense (now the National Syndromic Surveillance Program) includes, in the short term, a focus on data quality with an emphasis on stability, consistency, and reliability and, in the long term, increased capacity and innovation, new data sources and system functionality, and exploration of emerging technologies and analytics.",,"['Gould, Deborah W.', 'Walker, David', 'Yoon, Paula W.']",,,,
,PMC,"Exploiting lymphatic vessels for immunomodulation: Rationale, opportunities, and challenges()",http://dx.doi.org/10.1016/j.addr.2017.07.005,PMC6026542,,,"Lymphatic vessels are the primary route of communication from peripheral tissues to the immune system; as such, they represent an important component of local immunity. In addition to their transport functions, new immunomodulatory roles for lymphatic vessels and lymphatic endothelial cells have come to light in recent years, demonstrating that lymphatic vessels help shape immune responses in a variety of ways: promoting tolerance to self-antigens, archiving antigen for later presentation, dampening effector immune responses, and resolving inflammation, among others. In addition to these new biological insights, the growing field of immunoengineering has begun to explore therapeutic approaches to utilize or exploit the lymphatic system for immunotherapy.",,"['Maisel, Katharina', 'Sasso, Maria Stella', 'Potin, Lambert', 'Swartz, Melody A.']",,,,
,PMC,Binding Kinetics and Lateral Mobility of HSV-1 on End-Grafted Sulfated Glycosaminoglycans,http://dx.doi.org/10.1016/j.bpj.2017.06.028,PMC5607149,,,"Many viruses, including herpes simplex (HSV), are recruited to their host cells via interaction between their envelope glycoproteins and cell-surface glycosaminoglycans (GAGs). This initial attachment is of a multivalent nature, i.e., it requires the establishment of multiple bonds between amino acids of viral glycoproteins and sulfated saccharides on the GAG chain. To gain understanding of how this binding process is modulated, we performed binding kinetics and mobility studies using end-grafted GAG chains that mimic the end attachment of these chains to proteoglycans. Total internal reflection fluorescence microscopy was used to probe binding and release, as well as the diffusion of single HSV-1 particles. To verify the hypothesis that the degree of sulfation, but also the arrangement of sulfate groups along the GAG chain, plays a key role in HSV binding, we tested two native GAGs (chondroitin sulfate and heparan sulfate) and compared our results to chemically sulfated hyaluronan. HSV-1 recognized all sulfated GAGs, but not the nonsulfated hyaluronan, indicating that binding is specific to the presence of sulfate groups. Furthermore we observed that a notable fraction of GAG-bound virions exhibit lateral mobility, although the multivalent binding to the immobilized GAG brushes ensures firm virus attachment to the interface. Diffusion was faster on the two native GAGs, one of which, chondroitin sulfate, was also characterized by the highest association rate per GAG chain. This highlights the complexity of multivalent virus-GAG interactions and suggests that the spatial arrangement of sulfates along native GAG chains may play a role in modulating the characteristics of the HSV-GAG interaction. Altogether, these results, obtained with a minimal and well-controlled model of the cell membrane, provide, to our knowledge, new insights into the dynamics of the HSV-GAG interaction.",,"['Peerboom, Nadia', 'Block, Stephan', 'Altgärde, Noomi', 'Wahlsten, Olov', 'Möller, Stephanie', 'Schnabelrauch, Matthias', 'Trybala, Edward', 'Bergström, Tomas', 'Bally, Marta']",,,,
,PMC,Sensing viruses using terahertz nano-gap metamaterials,http://dx.doi.org/10.1364/BOE.8.003551,PMC5560824,,,"We demonstrate highly sensitive detection of viruses using terahertz split-ring resonators with various capacitive gap widths. Two types of viruses, with sizes ranging from 60 nm (PRD1) to 30 nm (MS2), were detected at low densities on the metamaterial surface. The dielectric constants of the virus layers in the THz frequency range were first measured using thick films, and the large values found identified them as efficient target substances for dielectric sensing. We observed the resonance-frequency shift of the THz metamaterial following deposition of the viruses on the surface at low-density. The resonance shift was higher for the MS2 virus, which has a relatively large dielectric constant. The frequency shift increases with surface density until saturation and the sensitivity is then obtained from the initial slope. Significantly, the sensitivity increases by about 13 times as the gap width in the metamaterials is decreased from 3 µm to 200 nm. This results from a combination of size-related factors, leading to field enhancement accompanying strong field localization.",,"['Park, S. J.', 'Cha, S. H.', 'Shin, G. A.', 'Ahn, Y. H.']",,,,
,PMC,High-dimensional CyTOF analysis of dengue virus–infected human DCs reveals distinct viral signatures,http://dx.doi.org/10.1172/jci.insight.92424,PMC5499363,,,"Dengue virus (DENV) is the most prevalent mosquito-borne virus causing human disease. Of the 4 DENV serotypes, epidemiological data suggest that DENV-2 secondary infections are associated with more severe disease than DENV-4 infections. Mass cytometry by time-of-flight (CyTOF) was used to dissect immune changes induced by DENV-2 and DENV-4 in human DCs, the initial targets of primary infections that likely affect infection outcomes. Strikingly, DENV-4 replication peaked earlier and promoted stronger innate immune responses, with increased expression of DC activation and migration markers and increased cytokine production, compared with DENV-2. In addition, infected DCs produced higher levels of inflammatory cytokines compared with bystander DCs, which mainly produced IFN-induced cytokines. These high-dimensional analyses during DENV-2 and DENV-4 infections revealed distinct viral signatures marked by different replication strategies and antiviral innate immune induction in DCs, which may result in different viral fitness, transmission, and pathogenesis.",,"['Hamlin, Rebecca E.', 'Rahman, Adeeb', 'Pak, Theodore R.', 'Maringer, Kevin', 'Mena, Ignacio', 'Bernal-Rubio, Dabeiba', 'Potla, Uma', 'Maestre, Ana M.', 'Fredericks, Anthony C.', 'Amir, El-ad D.', 'Kasarskis, Andrew', 'Ramos, Irene', 'Merad, Miriam', 'Fernandez-Sesma, Ana']",,,,
,PMC,Section 4: Immunopharmacology,http://dx.doi.org/10.1038/aps.2017.67,PMC5519253,,,,,,,,,
,PMC,Hyper Acute Demyelinating Encephalomyelitis of Childhood: A Rare Entity,http://dx.doi.org/10.4103/aian.AIAN_52_17,PMC5586132,28904469,CC BY-NC-SA,A young child with catastrophic neurological illness diagnosed as a rare variant of acute demyelinating encephalomyelitis (ADEM). She succumbed to her illness despite of aggressive and appropriate management. Malignant demyelinating encephalomyelitis should be considered in children who are refractory to the treatment of ADEM.,2017 Jul-Sep,"['Kushwaha, Suman', 'Gupta, Ashutosh', 'Agarwal, Neha', 'Chaturvedi, Sujata', 'Jha, Deepak']",Ann Indian Acad Neurol,,,
,PMC,"Prevalence of antibodies against the Middle East Respiratory Syndrome coronavirus, influenza A and B viruses among blood donors, Saudi Arabia",http://dx.doi.org/10.4103/atm.ATM_143_17,PMC5541973,28808497,CC BY-NC-SA,,2017 Jul-Sep,"['Alrashid, Manar', 'Taleb, Alanoud Abu', 'Hajeer, Ali', 'Arabi, Yaseen']",Ann Thorac Med,,,
,PMC,Identifying Personal Health Experience Tweets with Deep Neural Networks,http://dx.doi.org/10.1109/EMBC.2017.8037039,PMC5702551,,,"Twitter, as a social media platform, has become an increasingly useful data source for health surveillance studies, and personal health experiences shared on Twitter provide valuable information to the surveillance. Twitter data are known for their irregular usages of languages and informal short texts due to the 140 character limit, and for their noisiness such that majority of the posts are irrelevant to any particular health surveillance. These factors pose challenges in identifying personal health experience tweets from the Twitter data. In this study, we designed deep neural networks with 3 different architectural configurations, and after training them with a corpus of 8,770 annotated tweets, we used them to predict personal experience tweets from a set of 821 annotate tweets. Our results demonstrated a significant amount of improvement in predicting personal health experience tweets by deep neural networks over that by conventional classifiers: 37.5% in accuracy, 31.1% in precision, and 53.6% in recall. We believe that our method can be utilized in various health surveillance studies using Twitter as a data source.",,"['Jiang, Keyuan', 'Gupta, Ravish', 'Gupta, Matrika', 'Calix, Ricardo A.', 'Bernard, Gordon R.']",,,,
,PMC,Follow-up chest radiographic findings in patients with MERS-CoV after recovery,http://dx.doi.org/10.4103/ijri.IJRI_469_16,PMC5644332,29089687,CC BY-NC-SA,"PURPOSE: To evaluate the follow-up chest radiographic findings in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) who were discharged from the hospital following improved clinical symptoms. MATERIALS AND METHODS: Thirty-six consecutive patients (9 men, 27 women; age range 21–73 years, mean ± SD 42.5 ± 14.5 years) with confirmed MERS-CoV underwent follow-up chest radiographs after recovery from MERS-CoV. The 36 chest radiographs were obtained at 32 to 230 days with a median follow-up of 43 days. The reviewers systemically evaluated the follow-up chest radiographs from 36 patients for lung parenchymal, airway, pleural, hilar and mediastinal abnormalities. Lung parenchyma and airways were assessed for consolidation, ground-glass opacity (GGO), nodular opacity and reticular opacity (i.e., fibrosis). Follow-up chest radiographs were also evaluated for pleural thickening, pleural effusion, pneumothorax and lymphadenopathy. Patients were categorized into two groups: group 1 (no evidence of lung fibrosis) and group 2 (chest radiographic evidence of lung fibrosis) for comparative analysis. Patient demographics, length of ventilations days, number of intensive care unit (ICU) admission days, chest radiographic score, chest radiographic deterioration pattern (Types 1-4) and peak lactate dehydrogenase level were compared between the two groups using the student t-test, Mann-Whitney U test and Fisher's exact test. RESULTS: Follow-up chest radiographs were normal in 23 out of 36 (64%) patients. Among the patients with abnormal chest radiographs (13/36, 36%), the following were found: lung fibrosis in 12 (33%) patients GGO in 2 (5.5%) patients, and pleural thickening in 2 (5.5%) patients. Patients with lung fibrosis had significantly greater number of ICU admission days (19 ± 8.7 days; P value = 0.001), older age (50.6 ± 12.6 years; P value = 0.02), higher chest radiographic scores [10 (0-15.3); P value = 0.04] and higher peak lactate dehydrogenase levels (315-370 U/L; P value = 0.001) when compared to patients without lung fibrosis. CONCLUSION: Lung fibrosis may develop in a substantial number of patients who have recovered from Middle East respiratory syndrome coronavirus (MERS-CoV). Significantly greater number of ICU admission days, older age, higher chest radiographic scores, chest radiographic deterioration patterns and peak lactate dehydrogenase levels were noted in the patients with lung fibrosis on follow-up chest radiographs after recovery from MERS-CoV.",2017 Jul-Sep,"['Das, Karuna M', 'Lee, Edward Y', 'Singh, Rajvir', 'Enani, Mushira A', 'Al Dossari, Khalid', 'Van Gorkom, Klaus', 'Larsson, Sven G', 'Langer, Ruth D']",Indian J Radiol Imaging,,,
,PMC,Role of TGF-β in anti-rhinovirus immune responses in asthmatic patients,http://dx.doi.org/10.1016/j.jaci.2016.10.049,PMC5754331,28139316,CC BY-NC-ND,,2017 Jul,"['Bielor, Carina', 'Sopel, Nina', 'Maier, Anja', 'Blau, Ashley', 'Sharma, Himanshu', 'Vuorinen, Tytti', 'Kroß, Bettina', 'Mittler, Susanne', 'Graser, Anna', 'Mousset, Stephanie', 'Melichar, Volker O.', 'Kiefer, Alexander', 'Zimmermann, Theodor', 'Springel, Rebekka', 'Holzinger, Corinna', 'Trump, Sonja', 'Taka, Stella', 'Papadopoulos, Nikolaos G.', 'Weiss, Scott T.', 'Finotto, Susetta']",J Allergy Clin Immunol,,,
,PMC,Politics of Ebola and the critical role of global health diplomacy for the CARICOM,http://dx.doi.org/10.4103/jfmpc.jfmpc_75_17,PMC5787937,29416990,CC BY-NC-SA,"The 2014 Ebola epidemic was the largest in history, affecting Guinea, Liberia, Sierra Leone, Nigeria, and Mali in West Africa. The International Health Regulations are legally binding in 194 countries including all the member states of WHO “to prevent, protect against, control, and provide a public health response to the international spread of disease.” Since the Caribbean Community region heavily depends on tourism, a single case of the disease anywhere in the region could have serious negative consequences for the rest of the region's tourism industry. Global health diplomacy brings together the disciplines of public health, international affairs, management, law, and economics and focuses on negotiations that shape and manage the global policy environment for health. The regional institutes such as Caribbean Public Health Agency should play a more proactive and pivotal role in the creation of regional response teams in all the island nations collaborating with the departments of public health and epidemiology at the regional campuses of The University of the West Indies. The role of global health diplomacy and its practice should be encouraged to reach a consensus among the stakeholders considering the threat to the health security in the region. There is a need for the cadre of global health diplomats who has a critical understanding of health and also the practice of diplomacy since such serious health issues have implications at the global level in this globalized world.",2017 Jul-Sep,"Chattu, Vijay Kumar",J Family Med Prim Care,,,
,PMC,ITIM receptors: more than just inhibitors of platelet activation,http://dx.doi.org/10.1182/blood-2016-12-720185,PMC5562394,,,"Since their discovery, immunoreceptor tyrosine-based inhibition motif (ITIM)-containing receptors have been shown to inhibit signaling from immunoreceptor tyrosine-based activation motif (ITAM)-containing receptors in almost all hematopoietic cells, including platelets. However, a growing body of evidence has emerged demonstrating that this is an oversimplification, and that ITIM-containing receptors are versatile regulators of platelet signal transduction, with functions beyond inhibiting ITAM-mediated platelet activation. PECAM-1 was the first ITIM-containing receptor identified in platelets and appeared to conform to the established model of ITIM-mediated attenuation of ITAM-driven activation. PECAM-1 was therefore widely accepted as a major negative regulator of platelet activation and thrombosis for many years, but more recent findings suggest a more complex role for this receptor, including the facilitation of α(IIb)β(3)-mediated platelet functions. Since the identification of PECAM-1, several other ITIM-containing platelet receptors have been discovered. These include G6b-B, a critical regulator of platelet reactivity and production, and the noncanonical ITIM-containing receptor TREM-like transcript-1, which is localized to α-granules in resting platelets, binds fibrinogen, and acts as a positive regulator of platelet activation. Despite structural similarities and shared binding partners, including the Src homology 2 domain-containing protein-tyrosine phosphatases Shp1 and Shp2, knockout and transgenic mouse models have revealed distinct phenotypes and nonredundant functions for each ITIM-containing receptor in the context of platelet homeostasis. These roles are likely influenced by receptor density, compartmentalization, and as-yet unknown binding partners. In this review, we discuss the diverse repertoire of ITIM-containing receptors in platelets, highlighting intriguing new functions, controversies, and future areas of investigation.",,"['Coxon, Carmen H.', 'Geer, Mitchell J.', 'Senis, Yotis A.']",,,,
,PMC,Viral replication complexes are targeted by LC3-guided interferon-inducible GTPases,http://dx.doi.org/10.1016/j.chom.2017.06.005,PMC5591033,,,"All viruses with positive-sense RNA genomes replicate on membranous structures in the cytoplasm, called replication complexes (RCs). RCs provide an advantageous microenvironment for viral replication, but it is unknown how the host immune system counteracts these structures. Here we show that interferon-gamma (IFNG) disrupts the RC of murine norovirus (MNV) via evolutionarily conserved autophagy proteins and the induction of IFN-inducible GTPases, which are known to destroy the membrane of vacuoles containing bacteria, protists, or fungi. The MNV RC was marked by the microtubule-associated-protein-1-light-chain-3 (LC3) conjugation system of autophagy and then targeted by immunity-related GTPases (IRGs) and guanylate binding proteins (GBPs) upon their induction by IFNG. Further, the LC3 conjugation system and the IFN-inducible GTPases were necessary to inhibit MNV replication in mice and human cells. These data suggest that viral RCs can be marked and antagonized by a universal immune defense mechanism targeting diverse pathogens replicating in cytosolic membrane structures.",,"['Biering, Scott B.', 'Choi, Jayoung', 'Halstrom, Rachel A.', 'Brown, Hailey M.', 'Beatty, Wandy L.', 'Lee, Sanghyun', 'McCune, Broc T.', 'Dominici, Erin', 'Williams, Lelia E.', 'Orchard, Robert C.', 'Wilen, Craig B.', 'Yamamoto, Masahiro', 'Coers, Jörn', 'Taylor, Gregory A.', 'Hwang, Seungmin']",,,,
,PMC,Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses,http://dx.doi.org/10.1126/scitranslmed.aal3653,PMC5567817,,,"Emerging viral infections are difficult to control as heterogeneous members periodically cycle in and out of humans and zoonotic hosts, complicating the development of specific antiviral therapies and vaccines. Coronaviruses (CoVs) have a proclivity to spread rapidly into new host species causing severe disease. SARS-CoV and MERS-CoV successively emerged causing severe epidemic respiratory disease in immunologically naïve human populations throughout the globe. Broad-spectrum therapies capable of inhibiting CoV infections would address an immediate unmet medical need and could be invaluable in the treatment of emerging and endemic CoV infections. Here we show that a nucleotide prodrug GS-5734, currently in clinical development for treatment of Ebola virus disease, can inhibit SARS-CoV and MERS-CoV replication in multiple in vitro systems including primary human airway epithelial cell cultures with submicromolar IC(50) values. GS-5734 was also effective against bat-CoVs, prepandemic bat-CoVs and circulating contemporary human CoV in primary human lung cells, thus demonstrating broad-spectrum anti-CoV activity. In a mouse model of SARS-CoV pathogenesis, prophylactic and early therapeutic administration of GS-5734 significantly reduced lung viral load and improved clinical signs of disease as well as respiratory functions. These data provide substantive evidence that GS-5734 may prove effective against endemic MERS-CoV in the Middle East, circulating human CoV, and possibly most importantly, emerging CoV of the future.",,"['Sheahan, Timothy P.', 'Sims, Amy C.', 'Graham, Rachel L.', 'Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Case, James B.', 'Leist, Sarah R.', 'Pyrc, Krzysztof', 'Feng, Joy Y.', 'Trantcheva, Iva', 'Bannister, Roy', 'Park, Yeojin', 'Babusis, Darius', 'Clarke, Michael O.', 'Mackman, Richard L.', 'Spahn, Jamie E.', 'Palmiotti, Christopher A.', 'Siegel, Dustin', 'Ray, Adrian S.', 'Cihlar, Tomas', 'Jordan, Robert', 'Denison, Mark R.', 'Baric, Ralph S.']",,,,
,PMC,CD11a and CD49d enhance the detection of antigen-specific T cells following human vaccination,http://dx.doi.org/10.1016/j.vaccine.2017.06.013,PMC5551405,,,"BACKGROUND: Determining the efficacy of human vaccines that induce antigen-specific protective CD4 T cell responses against pathogens can be particularly challenging to evaluate. Surface expression of CD11a and CD49d has been shown to identify antigen-specific CD4 T cells against viral pathogens in mice. We hypothesized that CD11a and CD49d would also serve as markers of human antigen-specific T cells responding to vaccination. METHODS: A phase I vaccine trial enabled us to evaluate a novel gating strategy based on surface expression of CD11a and CD49d as a means of detecting antigen-specific, cytokine producing CD4 and CD8 T cells induced after vaccination of naïve individuals against leishmaniasis. Three study groups received LEISH-F3 recombinant protein combined with either squalene oil-in-water emulsion (SE) alone, SE with the synthetic TLR-4 ligand glucopyranosyl lipid adjuvant (GLA-SE), or SE with Salmonella minnesota-derived monophosphoryl lipid A (MPL-SE). Individuals were given 3 vaccine doses, on days 0, 28 and 168. RESULTS: Starting after the first vaccine dose, the frequency of both CD11a(hi)CD49d(+) CD4 and CD11a(hi)CD49d(+) CD8 T cells significantly increased over time throughout the 24-week trial. To confirm the role of CD11a(hi)CD49d(+) expression in the identification of the antigen-specific T cells, cytokine production was measured following LEISH-F3 stimulation. All of the IFN-γ, TNF-α, and IL-2 producing cells were found within the CD11a(hi)CD49d(+) population. CONCLUSIONS: Our results suggest that the change in the frequency of CD11a(hi)CD49d(+) T cells can be used to track antigen-specific CD4 and CD8 T cell responses following T cell-targeted vaccination.",,"['Christiaansen, Allison F.', 'Dixit, Upasna Gaur', 'Coler, Rhea N.', 'Beckmann, Anna Marie', 'Reed, Steven G.', 'Winokur, Patricia L.', 'Zimmerman, M. Bridget', 'Varga, Steven M.', 'Wilson, Mary E.']",,,,
,PMC,ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice,http://dx.doi.org/10.1016/j.vaccine.2017.05.032,PMC5516308,28579232,CC BY,"The Middle East respiratory syndrome coronavirus (MERS-CoV) has infected more than 1900 humans, since 2012. The syndrome ranges from asymptomatic and mild cases to severe pneumonia and death. The virus is believed to be circulating in dromedary camels without notable symptoms since the 1980s. Therefore, dromedary camels are considered the only animal source of infection. Neither antiviral drugs nor vaccines are approved for veterinary or medical use despite active research on this area. Here, we developed four vaccine candidates against MERS-CoV based on ChAdOx1 and MVA viral vectors, two candidates per vector. All vaccines contained the full-length spike gene of MERS-CoV; ChAdOx1 MERS vaccines were produced with or without the leader sequence of the human tissue plasminogen activator gene (tPA) where MVA MERS vaccines were produced with tPA, but either the mH5 or F11 promoter driving expression of the spike gene. All vaccine candidates were evaluated in a mouse model in prime only or prime-boost regimens. ChAdOx1 MERS with tPA induced higher neutralising antibodies than ChAdOx1 MERS without tPA. A single dose of ChAdOx1 MERS with tPA elicited cellular immune responses as well as neutralising antibodies that were boosted to a significantly higher level by MVA MERS. The humoral immunogenicity of a single dose of ChAdOx1 MERS with tPA was equivalent to two doses of MVA MERS (also with tPA). MVA MERS with mH5 or F11 promoter induced similar antibody levels; however, F11 promoter enhanced the cellular immunogenicity of MVA MERS to significantly higher magnitudes. In conclusion, our study showed that MERS-CoV vaccine candidates could be optimized by utilising different viral vectors, various genetic designs of the vectors, or different regimens to increase immunogenicity. ChAdOx1 and MVA vectored vaccines have been safely evaluated in camels and humans and these MERS vaccine candidates should now be tested in camels and in clinical trials.",2017 Jun 27,"['Alharbi, Naif Khalaf', 'Padron-Regalado, Eriko', 'Thompson, Craig P.', 'Kupke, Alexandra', 'Wells, Daniel', 'Sloan, Megan A.', 'Grehan, Keith', 'Temperton, Nigel', 'Lambe, Teresa', 'Warimwe, George', 'Becker, Stephan', 'Hill, Adrian V.S.', 'Gilbert, Sarah C.']",Vaccine,,,
,PMC,Overexpressed eNOS upregulates SIRT1 expression and protects mouse pancreatic β cells from apoptosis,http://dx.doi.org/10.3892/etm.2017.4669,PMC5526166,,,"Loss of sirtuin 1 (SIRT1) activity may be associated with metabolic diseases, including diabetes. The aim of the present study was to investigate the potential effects of overexpressed endothelial nitric oxide synthase (eNOS) on cell proliferation and apoptosis with SIRT1 activation in the Min6 mouse pancreatic β cell line. A pcDNA3.0-eNOS plasmid was constructed and transfected into Min6 cells for 24 h prior to harvesting. eNOS expression was validated and SIRT1 expression was detected following plasmid transfection using reverse transcription-quantitative polymerase chain reaction and western blot analysis, which demonstrated that the expression levels of eNOS and SIRT1 were significantly upregulated. Furthermore, the cell proliferation and cell apoptosis of the Min6 cells were evaluated, using a cell counting kit-8 assay and flow cytometry, respectively. The results suggested that overexpressed eNOS promoted cell proliferation and inhibited cell apoptosis in Min6 cells. The interaction between eNOS and SIRT1 was explored through co-immunoprecipitation, and it found that there was a strong interaction between eNOS and SIRT1. In conclusion, overexpressed eNOS may induce SIRT1 activation, which is implied to play a protective role in Min6 cells, and eNOS may be a new therapeutic target for diseases such as type 2 diabetes.",,"['Hu, Tingting', 'Chen, Ye', 'Jiang, Qian', 'Lin, Jun', 'Li, Hewei', 'Wang, Ping', 'Feng, Leping']",,,,
,PMC,Selective Activation of Type II Interferon Signaling by Zika Virus NS5 Protein,http://dx.doi.org/10.1128/JVI.00163-17,PMC5487581,,,"Severe complications of Zika virus (ZIKV) infection might be caused by inflammation, but how ZIKV induces proinflammatory cytokines is not understood. In this study, we show opposite regulatory effects of the ZIKV NS5 protein on interferon (IFN) signaling. Whereas ZIKV and its NS5 protein were potent suppressors of type I and type III IFN signaling, they were found to activate type II IFN signaling. Inversely, IFN-γ augmented ZIKV replication. NS5 interacted with STAT2 and targeted it for ubiquitination and degradation, but it had no influence on STAT1 stability or nuclear translocation. The recruitment of STAT1-STAT2-IRF9 to IFN-β-stimulated genes was compromised when NS5 was expressed. Concurrently, the formation of STAT1-STAT1 homodimers and their recruitment to IFN-γ-stimulated genes, such as the gene encoding the proinflammatory cytokine CXCL10, were augmented. Silencing the expression of an IFN-γ receptor subunit or treatment of ZIKV-infected cells with a JAK2 inhibitor suppressed viral replication and viral induction of IFN-γ-stimulated genes. Taken together, our findings provide a new mechanism by which the ZIKV NS5 protein differentially regulates IFN signaling to facilitate viral replication and cause diseases. This activity might be shared by a group of viral IFN modulators. IMPORTANCE Mammalian cells produce three types of interferons to combat viral infection and to control host immune responses. To replicate and cause diseases, pathogenic viruses have developed different strategies to defeat the action of host interferons. Many viral proteins, including the Zika virus (ZIKV) NS5 protein, are known to be able to suppress the antiviral property of type I and type III interferons. Here we further show that the ZIKV NS5 protein can also boost the activity of type II interferon to induce cellular proteins that promote inflammation. This is mediated by the differential effect of the ZIKV NS5 protein on a pair of cellular transcription factors, STAT1 and STAT2. NS5 induces the degradation of STAT2 but promotes the formation of STAT1-STAT1 protein complexes, which activate genes controlled by type II interferon. A drug that specifically inhibits the IFN-γ receptor or STAT1 shows an anti-ZIKV effect and might also have anti-inflammatory activity.",,"['Chaudhary, Vidyanath', 'Yuen, Kit-San', 'Chan, Jasper Fuk-Woo', 'Chan, Ching-Ping', 'Wang, Pei-Hui', 'Cai, Jian-Piao', 'Zhang, Shuo', 'Liang, Mifang', 'Kok, Kin-Hang', 'Chan, Chi-Ping', 'Yuen, Kwok-Yung', 'Jin, Dong-Yan']",,,,
,PMC,Deletion of a 197-Amino-Acid Region in the N-Terminal Domain of Spike Protein Attenuates Porcine Epidemic Diarrhea Virus in Piglets,http://dx.doi.org/10.1128/JVI.00227-17,PMC5487580,,,"We previously isolated a porcine epidemic diarrhea virus (PEDV) strain, PC177, by blind serial passaging of the intestinal contents of a diarrheic piglet in Vero cell culture. Compared with the highly virulent U.S. PEDV strain PC21A, the tissue culture-adapted PC177 (TC-PC177) contains a 197-amino-acid (aa) deletion in the N-terminal domain of the spike (S) protein. We orally inoculated neonatal, conventional suckling piglets with TC-PC177 or PC21A to compare their pathogenicities. Within 7 days postinoculation, TC-PC177 caused mild diarrhea and lower fecal viral RNA shedding, with no mortality, whereas PC21A caused severe clinical signs and 55% mortality. To investigate whether infection with TC-PC177 can induce cross-protection against challenge with a highly virulent PEDV strain, all the surviving piglets were challenged with PC21A at 3 weeks postinoculation. Compared with 100% protection in piglets initially inoculated with PC21A, 88% and 100% TC-PC177- and mock-inoculated piglets had diarrhea following challenge, respectively, indicating incomplete cross-protection. To investigate whether this 197-aa deletion was the determinant for the attenuation of TC-PC177, we generated a mutant (icPC22A-S1Δ197) bearing the 197-aa deletion from an infectious cDNA clone of the highly virulent PEDV PC22A strain (infectious clone PC22A, icPC22A). In neonatal gnotobiotic pigs, the icPC22A-S1Δ197 virus caused mild to moderate diarrhea, lower titers of viral shedding, and no mortality, whereas the icPC22A virus caused severe diarrhea and 100% mortality. Our data indicate that deletion of this 197-aa fragment in the spike protein can attenuate a highly virulent PEDV, but the virus may lose important epitopes for inducing robust protective immunity. IMPORTANCE The emerging, highly virulent PEDV strains have caused substantial economic losses worldwide. However, the virulence determinants are not established. In this study, we found that a 197-aa deletion in the N-terminal region of the S protein did not alter virus (TC-PC177) tissue tropism but reduced the virulence of the highly virulent PEDV strain PC22A in neonatal piglets. We also demonstrated that the primary infection with TC-PC177 failed to induce complete cross-protection against challenge by the highly virulent PEDV PC21A, suggesting that the 197-aa region may contain important epitopes for inducing protective immunity. Our results provide an insight into the role of this large deletion in virus propagation and pathogenicity. In addition, the reverse genetics platform of the PC22A strain was further optimized for the rescue of recombinant PEDV viruses in vitro. This breakthrough allows us to investigate other virulence determinants of PEDV strains and will provide knowledge leading to better control PEDV infections.",,"['Hou, Yixuan', 'Lin, Chun-Ming', 'Yokoyama, Masaru', 'Yount, Boyd L.', 'Marthaler, Douglas', 'Douglas, Arianna L.', 'Ghimire, Shristi', 'Qin, Yibin', 'Baric, Ralph S.', 'Saif, Linda J.', 'Wang, Qiuhong']",,,,
,PMC,Rubicon Modulates Antiviral Type I Interferon (IFN) Signaling by Targeting IFN Regulatory Factor 3 Dimerization,http://dx.doi.org/10.1128/JVI.00248-17,PMC5487567,,,"Rubicon is part of a Beclin-1-Vps34-containing autophagy complex. Rubicon induces antimicrobial responses upon Toll-like receptor (TLR) stimulation and functions as a feedback inhibitor to prevent unbalanced proinflammatory responses depending on dectin-1 signaling. However, the role played by Rubicon during antiviral immune responses, particularly the type I interferon (IFN) responses, remains largely unknown. Here, we report that Rubicon acts as a negative regulator for virus-triggered IFN signaling. Knockdown of Rubicon promoted type I interferon signaling and inhibited virus replication, while overexpression of Rubicon had the opposite effect. Rubicon specifically interacts with the interferon regulatory factor (IRF) association domain (IAD) of IRF3, and this interaction leads to inhibition of the dimerization of IRF3, which negatively regulates IFN-mediated antiviral response. Thus, our findings suggest the novel additional role of Rubicon as a negative regulator that inhibits the IFN signaling and cellular antiviral responses, providing a novel cellular mechanism of IRF3 inhibition. IMPORTANCE The type I IFN system is a critical innate immune response that protects organisms against virus infection. However, type I IFN signaling must be tightly regulated to avoid excessive production of IFNs. Hence, negative regulatory mechanisms for type I IFN signaling are important, and to date, several related molecules have been identified. Here, we show that Rubicon is a major negative regulator of type I IFN signaling, and unlike previous reports of cellular molecules that inhibit IRF3 activation via proteasomal degradation or dephosphorylation of IRF3, we show that Rubicon interacts with IRF3 and that ultimately this interaction leads to inhibition of the dimerization of IRF3. Thus, we identified a novel negative regulator of type I IFN signaling pathways and a novel cellular mechanism of IRF3 inhibition. The results of this study will increase our understanding of the role of negative-feedback mechanisms that regulate type I IFN signaling and maintain immune homeostasis.",,"['Kim, Jae-Hoon', 'Kim, Tae-Hwan', 'Lee, Hyun-Cheol', 'Nikapitiya, Chamilani', 'Uddin, Md Bashir', 'Park, Min-Eun', 'Pathinayake, Prabuddha', 'Lee, Eun Seo', 'Chathuranga, Kiramage', 'Herath, Thilina U. B.', 'Chathuranga, W. A. Gayan', 'Lee, Jong-Soo']",,,,
,PMC,A Naturally Occurring Recombinant Enterovirus Expresses a Torovirus Deubiquitinase,http://dx.doi.org/10.1128/JVI.00450-17,PMC5487566,,,"Enteroviruses (EVs) are implicated in a wide range of diseases in humans and animals. In this study, a novel enterovirus (enterovirus species G [EVG]) (EVG 08/NC_USA/2015) was isolated from a diagnostic sample from a neonatal pig diarrhea case and identified by using metagenomics and complete genome sequencing. The viral genome shares 75.4% nucleotide identity with a prototypic EVG strain (PEV9 UKG/410/73). Remarkably, a 582-nucleotide insertion, flanked by 3C(pro) cleavage sites at the 5′ and 3′ ends, was found in the 2C/3A junction region of the viral genome. This insertion encodes a predicted protease with 54 to 68% amino acid identity to torovirus (ToV) papain-like protease (PLP) (ToV-PLP). Structural homology modeling predicts that this protease adopts a fold and a catalytic site characteristic of minimal PLP catalytic domains. This structure is similar to those of core catalytic domains of the foot-and-mouth disease virus leader protease and coronavirus PLPs, which act as deubiquitinating and deISGylating (interferon [IFN]-stimulated gene 15 [ISG15]-removing) enzymes on host cell substrates. Importantly, the recombinant ToV-PLP protein derived from this novel enterovirus also showed strong deubiquitination and deISGylation activities and demonstrated the ability to suppress IFN-β expression. Using reverse genetics, we generated a ToV-PLP knockout recombinant virus. Compared to the wild-type virus, the ToV-PLP knockout mutant virus showed impaired growth and induced higher expression levels of innate immune genes in infected cells. These results suggest that ToV-PLP functions as an innate immune antagonist; enterovirus G may therefore gain fitness through the acquisition of ToV-PLP from a recombination event. IMPORTANCE Enteroviruses comprise a highly diversified group of viruses. Genetic recombination has been considered a driving force for viral evolution; however, recombination between viruses from two different orders is a rare event. In this study, we identified a special case of cross-order recombination between enterovirus G (order Picornavirales) and torovirus (order Nidovirales). This naturally occurring recombination event may have broad implications for other picornaviral and/or nidoviral species. Importantly, we demonstrated that the exogenous ToV-PLP gene that was inserted into the EVG genome encodes a deubiquitinase/deISGylase and potentially suppresses host cellular innate immune responses. Our results provide insights into how a gain of function through genetic recombination, in particular cross-order recombination, may improve the ability of a virus to evade host immunity.",,"['Shang, Pengcheng', 'Misra, Saurav', 'Hause, Ben', 'Fang, Ying']",,,,
,PMC,Grass Carp Reovirus VP41 Targets Fish MITA To Abrogate the Interferon Response,http://dx.doi.org/10.1128/JVI.00390-17,PMC5487562,,,"Although fish possess an efficient interferon (IFN) system to defend against aquatic virus infection, grass carp reovirus (GCRV) still causes hemorrhagic disease in grass carp. To date, GCRV's strategy for evading the fish IFN response is still unknown. Here, we report that GCRV VP41 inhibits fish IFN production by suppressing the phosphorylation of mediator of IFN regulatory factor 3 (IRF3) activation (MITA). First, the activation of the IFN promoter (IFNpro) stimulated by mitochondrial antiviral signaling protein (MAVS) and MITA was decreased by the overexpression of VP41, whereas such activation induced by TANK-binding kinase 1 (TBK1) was not affected. Second, VP41 was colocalized in the cellular endoplasmic reticulum (ER) and associated with MITA. Furthermore, as a phosphorylation substrate of TBK1, VP41 significantly decreased the phosphorylation of MITA. Truncation assays indicated that the transmembrane (TM) region of VP41 was indispensable for the suppression of IFNpro activity. Finally, after infection with GCRV, VP41 blunted the transcription of host IFN and facilitated viral RNA synthesis. Taken together, our findings suggest that GCRV VP41 prevents the fish IFN response by attenuating the phosphorylation of MITA for viral evasion. IMPORTANCE MITA is thought to act as an adaptor protein to facilitate the phosphorylation of IRF3 by TBK1 upon viral infection, and it plays a critical role in innate antiviral responses. Here, we report that GCRV VP41 colocalizes with MITA at the ER and reduces MITA phosphorylation by acting as a decoy substrate of TBK1, thus inhibiting IFN production. These findings reveal GCRV's strategy for evading the host IFN response for the first time.",,"['Lu, Long-Feng', 'Li, Shun', 'Wang, Zhao-Xi', 'Du, Si-Qi', 'Chen, Dan-Dan', 'Nie, Pin', 'Zhang, Yong-An']",,,,
,PMC,Antibody Preparations from Human Transchromosomic Cows Exhibit Prophylactic and Therapeutic Efficacy against Venezuelan Equine Encephalitis Virus,http://dx.doi.org/10.1128/JVI.00226-17,PMC5487544,,,"Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne RNA virus that causes low mortality but high morbidity rates in humans. In addition to natural outbreaks, there is the potential for exposure to VEEV via aerosolized virus particles. There are currently no FDA-licensed vaccines or antiviral therapies for VEEV. Passive immunotherapy is an approved method used to protect individuals against several pathogens and toxins. Human polyclonal antibodies (PAbs) are ideal, but this is dependent upon serum from convalescent human donors, which is in limited supply. Non-human-derived PAbs can have serious immunoreactivity complications, and when “humanized,” these antibodies may exhibit reduced neutralization efficiency. To address these issues, transchromosomic (Tc) bovines have been created, which can produce potent neutralizing human antibodies in response to hyperimmunization. In these studies, we have immunized these bovines with different VEEV immunogens and evaluated the protective efficacy of purified preparations of the resultant human polyclonal antisera against low- and high-dose VEEV challenges. These studies demonstrate that prophylactic or therapeutic administration of the polyclonal antibody preparations (TcPAbs) can protect mice against lethal subcutaneous or aerosol challenge with VEEV. Furthermore, significant protection against unrelated coinfecting viral pathogens can be conferred by combining individual virus-specific TcPAb preparations. IMPORTANCE With the globalization and spread or potential aerosol release of emerging infectious diseases, it will be critical to develop platforms that are able to produce therapeutics in a short time frame. By using a transchromosomic (Tc) bovine platform, it is theoretically possible to produce antigen-specific highly neutralizing therapeutic polyclonal human antibody (TcPAb) preparations in 6 months or less. In this study, we demonstrate that Tc bovine-derived Venezuelan equine encephalitis virus (VEEV)-specific TcPAbs are highly effective against VEEV infection that mimics not only the natural route of infection but also infection via aerosol exposure. Additionally, we show that combinatorial TcPAb preparations can be used to treat coinfections with divergent pathogens, demonstrating that the Tc bovine platform could be beneficial in areas where multiple infectious diseases occur contemporaneously or in the case of multipathogen release.",,"['Gardner, Christina L.', 'Sun, Chengqun', 'Luke, Thomas', 'Raviprakash, Kanakatte', 'Wu, Hua', 'Jiao, Jin-an', 'Sullivan, Eddie', 'Reed, Douglas S.', 'Ryman, Kate D.', 'Klimstra, William B.']",,,,
,PMC,Determination of suitable reference genes for RT-qPCR analysis of murine Cytomegalovirus in vivo and in vitro,http://dx.doi.org/10.1016/j.jviromet.2017.06.012,PMC6775634,,,"Reverse transcription quantitative PCR (RT-qPCR) is the most commonly used method to evaluate gene expression. Reliable qPCR results are highly dependent on accurate normalization using suitable reference genes. We investigated expression of commonly used reference genes during murine Cytomegalovirus (mCMV) infection and latency to determine those genes least perturbed by infection. Following mCMV infection in BALB/c mice, lung, salivary gland, liver, spleen and kidney were evaluated. Liver sinusoidal endothelial cells and NIH-3T3 cells were also evaluated. RT-qPCR was performed during acute and latent mCMV infection for 11 commonly used reference genes with comparisons made to uninfected samples. Normfinder, BestKeeper, GeNorm and the comparative delta CT method produced comparable analyses that were combined in RefFinder to generate an overall ranking. Ppia, B2m and Gapdh are the most stable reference genes for in vitro infection studies. For in vivo studies the most suitable reference genes were highly tissue and cell type dependent. Comparing infected and uninfected groups revealed viral influence on transcription of some genes. We provide reference gene guidelines for investigations of gene expression for mCMV Smith strain infection of Balb/cJ mice or NIH-3T3 cells. These results also suggest careful consideration of reference genes for different host tissues evaluated.",,"['Griessl, Marion', 'Gutknecht, Michael', 'Cook, Charles H']",,,,
,PMC,The liver is a metabolic and immunologic organ: a reconsideration of metabolic decompensation due to infection in inborn errors of metabolism (IEM),http://dx.doi.org/10.1016/j.ymgme.2017.06.010,PMC5553615,,,"Metabolic decompensation in inborn errors of metabolism (IEM) is characterized by a rapid deterioration in metabolic status leading to life-threatening biochemical perturbations (e.g. hypoglycemia, hyperammonemia, acidosis, organ failure). Infection is the major cause of metabolic decompensation in patients with IEM. We hypothesized that activation of the immune system during infection leads to further perturbations in end-organ metabolism resulting in increased morbidity. To address this, we established model systems of metabolic decompensation due to infection. Using these systems, we have described the pathologic mechanisms of metabolic decompensation as well as changes in hepatic metabolic reserve associated with infection. First and foremost, our studies have demonstrated that the liver experiences a significant local innate immune response during influenza infection that modulates hepatic metabolism. Based on these findings, we are the first to suggest that the role of the liver as a metabolic and immunologic organ is central in the pathophysiology of metabolic decompensation due to infection in IEM. The dual function of the liver as a major metabolic regulator and a lymphoid organ responsible for immunosurveillance places this organ at risk for hepatotoxicity. Mobilization of hepatic reserve and the regenerative capacity of a healthy liver compensates for this calculated risk. However, activation of the hepatic innate immune system may be deleterious in IEM. Based on this assertion, strategies aimed at modulating the innate immune response may be a viable target for intervention in the treatment of hepatic metabolic decompensation.",,"['Tarasenko, Tatiana N.', 'McGuire, Peter J.']",,,,
,PMC,Molecular Characterization of Mycoplasma pneumoniae Infections in Two Rural Populations of Thailand from 2009 to 2012,http://dx.doi.org/10.1128/JCM.00350-17,PMC5483925,,,"Studies on Mycoplasma pneumoniae in Thailand have focused on urban centers and have not included molecular characterization. In an attempt to provide a more comprehensive understanding of this organism, we conducted a systematic random sampling to identify 3,000 nasopharyngeal swab specimens collected from January 2009 through July 2012 during population-based surveillance for influenza-like illness in two rural provinces. M. pneumoniae was detected by real-time PCR in 175 (5.8%) specimens. Genotyping was performed using the major adhesion protein (P1) and multilocus variable-number tandem-repeat analysis (MLVA). Of the 157 specimens typed, 97 were P1 type 1 and 60 were P1 type 2. Six different MLVA profiles were identified in 149 specimens, with 4/5/7/2 (40%) and 3/5/6/2 (26%) predominating. There was no discrete seasonality to M. pneumoniae infections. Examination of the 23S rRNA sequence for known polymorphisms conferring macrolide resistance revealed that all 141 tested to possess the genotype associated with macrolide susceptibility.",,"['Whistler, Toni', 'Sawatwong, Pongpun', 'Diaz, Maureen H.', 'Benitez, Alvaro J.', 'Wolff, Bernard J.', 'Sapchookul, Patranuch', 'Thamthitiwat, Somsak', 'Winchell, Jonas M.']",,,,
,PMC,"Evaluation of the 2010 National Vaccine Plan Mid-course Review: Recommendations From the National Vaccine Advisory Committee: Approved by the National Vaccine Advisory Committee on February 7, 2017",http://dx.doi.org/10.1177/0033354917714233,PMC5507433,,,,,,,,,
,PMC,Federal Travel Restrictions to Prevent Disease Transmission in the United States: an analysis of requested travel restrictions,http://dx.doi.org/10.1016/j.tmaid.2017.06.007,PMC5605433,,,"BACKGROUND: Individuals with certain communicable diseases may pose risks to the health of the traveling public; there has been documented transmission on commercial aircraft of tuberculosis (TB), measles, and severe acute respiratory syndrome (SARS). Federal public health travel restrictions (PHTR) prevent commercial air or international travel of persons with communicable diseases that pose a public health threat. METHODS: We described demographics and clinical characteristics of all cases considered for PHTR because of suspected or confirmed communicable disease from May 22, 2007, to December 31, 2015. RESULTS: We reviewed 682 requests for PHTR; 414 (61%) actions were completed to place 396 individuals on PHTR. The majority (>99%) had suspected (n=27) or confirmed (n=367) infectious pulmonary TB; 58 (16%) had multidrug-resistant-TB. There were 128 (85%) interceptions that prevented the initiation or continuation of travel. PHTR were removed for 310 (78%) individuals after attaining noninfectious status and 86 (22%) remained on PHTR at the end of the analysis period. CONCLUSIONS: PHTR effectively prevent exposure during commercial air travel to persons with potentially infectious diseases. In addition, they are effective tools available to public health agencies to prevent commercial travel of individuals with certain communicable diseases and possibly reconnect them with public health authorities.",,"['Jungerman, M. Robynne', 'Vonnahme, Laura A.', 'Washburn, Faith', 'Alvarado-Ramy, Francisco']",,,,
,PMC,Serum Derived Transfer Factor Stimulates the Innate Immune System to Improve Survival Traits in High Risk Pathogen Scenarios,http://dx.doi.org/10.1002/ddr.21392,PMC5600497,,,"Transfer Factors (TFs) are low molecular weight (<5,000 daltons) biological response mediators. In the present study, a serum derived TF improved the ability of the recipient animal ability to survive high-risk infectious challenges (salmonellosis and canine parvoviral enteritis (CPV)) by altering the host cytokine response profile. Mice mortally challenged with 5,000 colony-forming units of Salmonella experienced a group mortality of 73% while mice treated with a single 5 mg dose of the TF demonstrated a significant decrease in morbidity (7%, p ≤ 0.01). The splenic bacterial load in untreated mice was over 10,000 times higher than that in the TF treated mice. Twenty-four hours post-administration, the treated murine population expressed a rapid temporal increase in serum IL-6 (26-fold) and INF-γ (77-fold) concentrations. IL-6 can act as a critical signal regulating action against bacterial pathogens. A comparative double-blind study performed using dogs confirmed to be undergoing a canine parvovirus challenge showed that when conventional supportive therapy was supplemented with a single 5 mg TF dose there was a reduction (p ≤ 0.01) in group mortality (68% of the TF treated group survived versus 32% of the placebo group), an observation consistent with the observed increase in INF-γ, a cytokine associated with promoting antiviral activity.",,"['Willeford, Bridget V.', 'Shapiro-Dunlap, Trudy', 'Willeford, Kenneth O.']",,,,
,PMC,Estimating Influenza Vaccine Effectiveness With the Test-Negative Design Using Alternative Control Groups: A Systematic Review and Meta-Analysis,http://dx.doi.org/10.1093/aje/kwx251,PMC5860156,,,"One important assumption in case-control studies is that control selection should be independent of exposure. Nevertheless, it has been hypothesized that virus interference might lead to a correlation between receipt of influenza vaccination and increased risk of infection with other respiratory viruses. We investigated whether such a phenomenon might affect a study design commonly used to estimate influenza vaccine effectiveness (VE). We searched publications in MEDLINE, PubMed, and Web of Science. We identified 12 studies using the test-negative design (2011–2017) that reported VE estimates separately derived by 3 alternative control groups: 1) all patients testing negative for influenza (FLU), VE(FLU−); 2) patients who tested positive for other/another respiratory virus (ORV), VE(ORV+); and 3) patients who tested negative for all viruses in the panel (PAN), VE(PAN−). These included VE estimates from 7 countries for all age groups from 2003/2004 to 2013/2014. We observed no difference in vaccination coverage between the ORV-positive and PAN-negative control groups. A total of 63 VE(FLU−) estimates, 62 VE(ORV+) estimates, and 33 VE(PAN−) estimates were extracted. Pooled estimates of the difference in VE (ΔVE) were very similar between groups. In meta-regression, no association was found between the selection of control group and VE estimates. In conclusion, we did not find any differences in VE estimates based on the choice of control group.",,"['Feng, Shuo', 'Cowling, Benjamin J', 'Kelly, Heath', 'Sullivan, Sheena G']",,,,
,PMC,Identification of a coumarin-based antihistamine-like small molecule as an anti-filoviral entry inhibitor,http://dx.doi.org/10.1016/j.antiviral.2017.06.015,PMC5666694,,,"Filoviruses, consisting of Ebola virus, Marburg virus and Cuevavirus, cause severe hemorrhagic fevers in humans with high mortality rates up to 90%. Currently, there is no approved vaccine or therapy available for the prevention and treatment of filovirus infection in humans. The recent 2013–2015 West African Ebola epidemic underscores the urgency to develop antiviral therapeutics against these infectious diseases. Our previous study showed that GPCR antagonists, particularly histamine receptor antagonists (antihistamines) inhibit Ebola and Marburg virus entry. In this study, we screened a library of 1220 small molecules with predicted antihistamine activity, identified multiple compounds with potent inhibitory activity against entry of both Ebola and Marburg viruses in human cancer cell lines, and confirmed their anti-Ebola activity in human primary cells. These small molecules target a late-stage of Ebola virus entry. Further structure-activity relationship studies around one compound (cp19) reveal the importance of the coumarin fused ring structure, especially the hydrophobic substituents at positions 3 and/or 4, for its antiviral activity, and this identified scaffold represents a favorable starting point for the rapid development of anti-filovirus therapeutic agents.",,"['Cheng, Han', 'Schafer, Adam', 'Soloveva, Veronica', 'Gharaibeh, Dima', 'Kenny, Tara', 'Retterer, Cary', 'Zamani, Rouzbeh', 'Bavari, Sina', 'Peet, Norton P.', 'Rong, Lijun']",,,,
,PMC,Protective and pathological immunity during CNS infections,http://dx.doi.org/10.1016/j.immuni.2017.06.012,PMC5662000,,,"The concept of immune privilege of the central nervous system (CNS) has dominated the study of inflammatory processes in the brain. However, clinically relevant models have highlighted the innate pathways that limit pathogen invasion of the CNS and that adaptive immunity mediates control of many neural infections. Because protective responses can result in bystander damage there are regulatory mechanisms that balance protective and pathological inflammation but which may also allow microbial persistence. The focus of this review is to consider the host-pathogen interactions that influence neurotropic infections and to highlight advances in understanding of innate and adaptive mechanisms of resistance as key determinants of the outcome of CNS infection. Advances in these areas have broadened our comprehension of how the immune system functions in the brain and can readily overcome immune privilege.",,"['Klein, Robyn S.', 'Hunter, Christopher A.']",,,,
,PMC,Multiplex Respiratory Virus Testing for Antimicrobial Stewardship: A Prospective Assessment of Antimicrobial Use and Clinical Outcomes Among Hospitalized Adults,http://dx.doi.org/10.1093/infdis/jix288,PMC5853820,,,"BACKGROUND: Respiratory tract infections are frequent causes of hospitalization and initiation of empirical antimicrobial therapy. Testing for a broad panel of respiratory viruses has been advocated as a useful tool for antibiotic stewardship. We conducted a prospective observational study to assess the impact of rapid viral test results on antimicrobial prescriptions and clinical outcomes among hospitalized adults. METHODS: Eight hundred patients admitted with respiratory symptoms were tested by a 12-virus respiratory panel (RVP) during 3 consecutive winters in Montreal, Canada. The primary outcome measure was change in antimicrobial prescriptions (ie, de-escalation of empirical antimicrobial therapy or commencement of new antimicrobial therapy) after RVP results were available. Clinical outcomes were also assessed. RESULTS: Influenza virus was identified in 53% of individuals in the study population, and other viruses were identified in 10%. Influenza virus positivity was associated with shorter duration of hospitalization and appropriate antiviral management. Antibiotic management was most significantly correlated with radiographic suspicion of pneumonia and less so with results of the RVP. Positivity for viruses other than influenza virus was not correlated with significantly different outcomes. CONCLUSIONS: Physicians respond to results of testing for influenza virus when managing hospitalized adult patients but respond less to test results for other viruses. These data can inform the design of stewardship interventions and the selection of viral testing panels for hospitalized patients.",,"['Semret, Makeda', 'Schiller, Ian', 'Jardin, Barbara Ann', 'Frenette, Charles', 'Loo, Vivian G', 'Papenburg, Jesse', 'McNeil, Shelly A', 'Dendukuri, Nandini']",,,,
,PMC,RosettaES: A greedy sampling strategy enabling automated interpretation of difficult cryoEM maps,http://dx.doi.org/10.1038/nmeth.4340,PMC6009829,,,"Accurate atomic modeling into cryoEM maps is a major challenge due to the moderate resolution of most datasets. We present RosettaES a method which, by enumerating a large space of backbone conformations consistent with the data, is able to identify near-native conformations in 85% of benchmark cases, including all shorter than 35 residues. We use this method in determining three structures that were unsolvable by expert structural biologists.",,"['Frenz, Brandon', 'Walls, Alexandra C.', 'Egelman, Edward H.', 'Veesler, David', 'DiMaio, Frank']",,,,
,PMC,Virus-induced inflammasome activation is suppressed by prostaglandin D(2)/DP1 signaling,http://dx.doi.org/10.1073/pnas.1704099114,PMC5502630,,,"Prostaglandin D2 (PGD(2)), an eicosanoid with both pro- and anti-inflammatory properties, is the most abundantly expressed prostaglandin in the brain. Here we show that PGD(2) signaling through the D-prostanoid receptor 1 (DP1) receptor is necessary for optimal microglia/macrophage activation and IFN expression after infection with a neurotropic coronavirus. Genome-wide expression analyses indicated that PGD(2)/DP1 signaling is required for up-regulation of a putative inflammasome inhibitor, PYDC3, in CD11b(+) cells in the CNS of infected mice. Our results also demonstrated that, in addition to PGD(2)/DP1 signaling, type 1 IFN (IFN-I) signaling is required for PYDC3 expression. In the absence of Pydc3 up-regulation, IL-1β expression and, subsequently, mortality were increased in infected DP1(−/−) mice. Notably, survival was enhanced by IL1 receptor blockade, indicating that the effects of the absence of DP1 signaling on clinical outcomes were mediated, at least in part, by inflammasomes. Using bone marrow-derived macrophages in vitro, we confirmed that PYDC3 expression is dependent upon DP1 signaling and that IFN priming is critical for PYDC3 up-regulation. In addition, Pydc3 silencing or overexpression augmented or diminished IL-1β secretion, respectively. Furthermore, DP1 signaling in human macrophages also resulted in the up-regulation of a putative functional analog, POP3, suggesting that PGD(2) similarly modulates inflammasomes in human cells. These findings demonstrate a previously undescribed role for prostaglandin signaling in preventing excessive inflammasome activation and, together with previously published results, suggest that eicosanoids and inflammasomes are reciprocally regulated.",,"['Vijay, Rahul', 'Fehr, Anthony R.', 'Janowski, Ann M.', 'Athmer, Jeremiah', 'Wheeler, Dorthea L.', 'Grunewald, Matthew', 'Sompallae, Ramakrishna', 'Kurup, Samarchith P.', 'Meyerholz, David K.', 'Sutterwala, Fayyaz S.', 'Narumiya, Shuh', 'Perlman, Stanley']",,,,
,PMC,Δ20 IFITM2 differentially restricts X4 and R5 HIV-1,http://dx.doi.org/10.1073/pnas.1619640114,PMC5502592,,,"CCR5 (R5)-tropic, but not CXCR4 (X4)-tropic, HIV-1 is associated with primary HIV-1 infection and transmission. Recent studies have shown that IFN-induced transmembrane (IFITM) proteins, including IFITM1, IFITM2, and IFITM3, restrict a broad range of viruses. Here, we demonstrate that an IFITM2 isoform (Δ20 IFITM2) lacking 20 amino acids at the N terminus differentially restricts X4 and R5 HIV-1. Δ20 IFITM2 suppresses replication of X4 HIV-1 strains by inhibiting their entry. High levels of Δ20 IFITM2 expression could be detected in CD4(+) T cells and in monocytes. Infection of X4 viruses in monocyte-derived macrophages and dendritic cells is enhanced upon depletion of IFITM2 isoforms. Furthermore, we also show that coreceptor use is the determining factor for differential HIV-1 restriction of Δ20 IFITM2. When we replace the C terminus of CCR5 with the C terminus of CXCR4, R5 viruses become more susceptible to Δ20 IFITM2-mediated restriction. In contrast to previous studies, our research reveals that neither X4 nor R5 HIV-1 is suppressed by IFITM2 and IFITM3. The multifactor gatekeeping model has been proposed to explain restriction of X4 viruses in the early stage of HIV-1 diseases. Our findings indicate that Δ20 IFITM2 may serve as a major contributor to this gatekeeping mechanism.",,"['Wu, Wan-Lin', 'Grotefend, Christopher Robert', 'Tsai, Ming-Ting', 'Wang, Yi-Ling', 'Radic, Vladimir', 'Eoh, Hyungjin', 'Huang, I-Chueh']",,,,
,PMC,Apoptosis and necroptosis as host defense strategies to prevent viral infection,http://dx.doi.org/10.1016/j.tcb.2017.05.007,PMC5653411,,,"Antiviral transcriptional responses and regulated cell death are critical components of the host response to virus infection. However, in contrast to the signaling pathways that promote antiviral transcription, those that initiate cell death following virus infection remain less understood. Several recent studies identified pattern recognition receptors (PRRs) of the mammalian innate immune system that activate cell death pathways. These same receptors also have established roles in the induction of antiviral gene expression. In this review, we discuss the mechanisms by which PRRs can serve dual roles as initiators of inflammatory gene expression and inducers of apoptosis and necroptosis following virus infection.",,"['Orzalli, Megan H.', 'Kagan, Jonathan C.']",,,,
,PMC,Delineating antibody recognition against Zika virus during natural infection,http://dx.doi.org/10.1172/jci.insight.93042,PMC5470883,,,"Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that shares a considerable degree of homology with dengue virus (DENV). Here, we examined longitudinal antibody response against ZIKV during natural infection in 2 convalescent individuals. By decomposing the antibody recognition into DI/DII and DIII of the E glycoprotein, we showed their development in humans followed a spatiotemporal hierarchy. Plasma binding to DI/DII appeared to peak and wane during early infection with extensive cross-reactivity with DI/DII of DENV. Binding to DIII, however, peaked early but persisted months into the infection without detectable cross-reactivity with DIII of DENV. A clear trend of increase in DIII-specific neutralizing activity was observed over the course of infection. mAbs isolated during early infection are largely DI/DII specific, weakly neutralizing, and highly cross-reactive with DENV, while those from later infection are more diverse in recognition, potently neutralizing, and ZIKV specific. The most potent neutralizing mAb targeting the DIII provided 100% protection in mice from lethal ZIKV infection and could therefore serve as a promising candidate for antibody-based therapy and prevention. The dynamic features unveiled here will assist us to better understand the pathogenesis of ZIKV infection and inform rational design of vaccines.",,"['Yu, Lei', 'Wang, Ruoke', 'Gao, Fei', 'Li, Min', 'Liu, Jianying', 'Wang, Jian', 'Hong, Wenxin', 'Zhao, Lingzhai', 'Wen, Yingfen', 'Yin, Chibiao', 'Wang, Hua', 'Zhang, Qi', 'Li, Yangyang', 'Zhou, Panpan', 'Zhang, Rudian', 'Liu, Yang', 'Tang, Xiaoping', 'Guan, Yongjun', 'Qin, Cheng-Feng', 'Chen, Ling', 'Shi, Xuanling', 'Jin, Xia', 'Cheng, Gong', 'Zhang, Fuchun', 'Zhang, Linqi']",,,,
,PMC,SARS‐unique fold in the Rousettus bat coronavirus HKU9,http://dx.doi.org/10.1002/pro.3208,PMC5563143,,,"The coronavirus nonstructural protein 3 (nsp3) is a multifunctional protein that comprises multiple structural domains. This protein assists viral polyprotein cleavage, host immune interference, and may play other roles in genome replication or transcription. Here, we report the solution NMR structure of a protein from the “SARS‐unique region” of the bat coronavirus HKU9. The protein contains a frataxin fold or double‐wing motif, which is an α + β fold that is associated with protein/protein interactions, DNA binding, and metal ion binding. High structural similarity to the human severe acute respiratory syndrome (SARS) coronavirus nsp3 is present. A possible functional site that is conserved among some betacoronaviruses has been identified using bioinformatics and biochemical analyses. This structure provides strong experimental support for the recent proposal advanced by us and others that the “SARS‐unique” region is not unique to the human SARS virus, but is conserved among several different phylogenetic groups of coronaviruses and provides essential functions.",,"['Hammond, Robert G.', 'Tan, Xuan', 'Johnson, Margaret A.']",,,,
,PMC,Making the Mark: The Role of Adenosine Modifications in the Lifecycle of RNA Viruses,http://dx.doi.org/10.1016/j.chom.2017.05.008,PMC5555051,,,"Viral epitranscriptomics is a newly emerging field that has identified unique roles for RNA modifications in modulating lifecycles of RNA viruses. Despite the observation of a handful of modified viral RNAs five decades ago, very little was known about how these modifications regulate viral lifecycles, until recently. Here we review the pro- and anti-viral effects of methyl-6-adenosine in distinct viral life cycles, the role of 2′ O-methyl modifications in RNA stability and innate immune sensing, and functions of adenosine to inosine modifications in retroviral life cycles. With roles for over 100 modifications in RNA still unknown, this is a rapidly emerging field that is destined to suggest novel antiviral therapies.",,"['Gonzales-van Horn, Sarah R.', 'Sarnow, Peter']",,,,
,PMC,"Cytotoxic lymphocytes and atherosclerosis: significance, mechanisms and therapeutic challenges",http://dx.doi.org/10.1111/bph.13845,PMC5660002,,,"Cytotoxic lymphocytes encompass natural killer lymphocytes (cells) and cytotoxic T cells that include CD8+ T cells, natural killer (NK) T cells, γ, δ (γδ)‐T cells and human CD4 + CD28− T cells. These cells play critical roles in inflammatory diseases and in controlling cancers and infections. Cytotoxic lymphocytes can be activated via a number of mechanisms that may involve dendritic cells, macrophages, cytokines or surface proteins on stressed cells. Upon activation, they secrete pro‐inflammatory cytokines as well as anti‐inflammatory cytokines, chemokines and cytotoxins to promote inflammation and the development of atherosclerotic lesions including vulnerable lesions, which are strongly implicated in myocardial infarctions and strokes. Here, we review the mechanisms that activate and regulate cytotoxic lymphocyte activity, including activating and inhibitory receptors, cytokines, chemokine receptors‐chemokine systems utilized to home to inflamed lesions and cytotoxins and cytokines through which they affect other cells within lesions. We also examine their roles in human and mouse models of atherosclerosis and the mechanisms by which they exert their pathogenic effects. Finally, we discuss strategies for therapeutically targeting these cells to prevent the development of atherosclerotic lesions and vulnerable plaques and the challenge of developing highly targeted therapies that only minimally affect the body's immune system, avoiding the complications, such as increased susceptibility to infections, which are currently associated with many immunotherapies for autoimmune diseases. LINKED ARTICLES: This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc",,"['Kyaw, Tin', 'Peter, Karlheinz', 'Li, Yi', 'Tipping, Peter', 'Toh, Ban‐Hock', 'Bobik, Alex']",,,,
,PMC,Assessment of Healthcare Worker Protocol Deviations and Self-Contamination During Personal Protective Equipment Donning and Doffing,http://dx.doi.org/10.1017/ice.2017.121,PMC6263164,,,"OBJECTIVE. To evaluate healthcare workers’ (HCWs) risk of self-contamination when donning and doffing personal protective equipment (PPE) using fluorescence and MS2 bacteriophage. DESIGN. Prospective pilot study. SETTING. Tertiary care hospital. PARTICIPANTS. 36 HCWs: 18 donned/doffed contact precautions (CP) PPE and 18 donned/doffed Ebola virus disease (EVD) PPE. INTERVENTIONS. HCWs donned PPE according to standard protocols. Fluorescent liquid and MS2 bacteriophage were applied to HCWs. HCWs then doffed their PPE. After doffing, HCWs were scanned for fluorescence and swabbed for MS2. MS2 detection was performed using reverse transcriptase PCR. The donning and doffing processes were videotaped and protocol deviations were recorded. RESULTS. 27% of EVD PPE HCWs and 50% of CP PPE HCWs made ≥1 protocol deviation while donning. 100% of EVD PPE HCWs and 67% of CP PPE HCWs made ≥1 protocol deviation while doffing (p=0.02). The median number of doffing protocol deviations among EVD PPE HCWs was 4, vs. 1 among CP PPE HCWs. 15 EVD PPE protocol deviations were committed by doffing assistants and/or trained observers. Fluorescence was detected on 8 (44%) of EVD PPE HCWs and 5 (28%) CP PPE HCWs, most commonly on hands. MS2 was recovered from 2 (11%) EVD PPE HCWs and 3 (17%) CP PPE HCWs. CONCLUSIONS. Protocol deviations were common during both EVD and CP PPE doffing, and some deviations during EVD PPE doffing were committed by the HCWs’ doffing assistant and/or trained observer. Self-contamination was common. PPE donning/doffing are complex and deserve additional study.",,"['Kwon, Jennie H.', 'Burnham, Carey-Ann D.', 'Reske, Kimberly A.', 'Liang, Stephen Y.', 'Hink, Tiffany', 'Wallace, Meghan A.', 'Shupe, Angela', 'Seiler, Sondra', 'Cass, Candice', 'Fraser, Victoria J.', 'Dubberke, Erik R.', None]",,,,
,PMC,Immunogenicity of mumps virus vaccine candidates matching circulating genotypes in the United States and China,http://dx.doi.org/10.1016/j.vaccine.2017.05.084,PMC5785236,,,"Mumps virus (MuV) causes acute infection in humans with characteristic swelling of the parotid gland. While vaccination has greatly reduced the incidence of MuV infection, there have been multiple large outbreaks of mumps virus (MuV) in highly vaccinated populations. The most common vaccine strain, Jeryl Lynn, belongs to genotype A, which is no longer a circulating genotype. We have developed two vaccine candidates that match the circulating genotypes in the United States (genotype G) and China (genotype F). We found that there was a significant decrease in the ability of the Jeryl Lynn vaccine to produce neutralizing antibody responses to non-matched viruses, when compared to either of our vaccine candidates. Our data suggests that an updated vaccine may allow for better immunity against the circulating MuV genotypes G and F.",,"['Zengel, James', 'Phan, Shannon I.', 'Pickar, Adrian', 'Xu, Pei', 'He, Biao']",,,,
,PMC,"Seroprevalence of antibodies to astrovirus in chickens in Grenada, West Indies",http://dx.doi.org/10.14202/vetworld.2017.636-639,PMC5499080,28717315,CC BY,"AIM: Chicken astroviruses (CAstV) are known to cause mild gastroenteritis, growth depression, and even mortality in poultry, especially in chickens, turkeys, and ducks. To the best our knowledge, there is no published information on CAstV in Grenada. This study was conducted to determine the prevalence of astrovirus in chickens in Grenada. MATERIALS AND METHODS: Blood samples from 366 indigenous chickens and 92 commercial chicken layers were collected from all parishes of the island and tested for antibodies against CAstV using commercial enzyme-linked immunosorbent assay. RESULTS: The seroprevalence of antibodies against astrovirus was 57.6% (95%, Confidence interval [CI]: 47.4-67.2) in commercial layers and 61.5% (95%, CI: 56.4-66.3) in indigenous chickens. The results show the presence of infection throughout the island. CONCLUSION: The results show the infection with CAstV in approximately half of the chicken population in Grenada. This is the first report on the prevalence of CAstV in chickens in Grenada and the Caribbean region.",2017 Jun 13,"['Sharma, Ravindra Nath', 'Dufayet, Romane', 'Maufras, Thomas', 'Connell, Kathryn O’', 'Tiwari, Keshaw']",Vet World,,,
,PMC,Rapid detection of tomato leaf curl Bengaluru virus through loop mediated isothermal amplification assay,http://dx.doi.org/10.1007/s13337-017-0385-5,PMC5684993,,,"A loop-mediated isothermal amplification (LAMP) technique was employed to develop a simple and rapid method for the detection of tomato leaf curl Bangalore virus (ToLCBaV) in diseased plants of tomato (Solanum lycopersicum). Six sets of primers were designed for LAMP technique targeting the conserved AC1 region and successfully detected ToLCBaV. No reaction was detected in the tissues of healthy plants by either the LAMP or the polymerase chain reaction (PCR). The LAMP products can be visualized by presence or absence of turbidity and staining (0.2 μL for 25 μL LAMP product) directly in the tube with nucleic acid stain dye which allowed easy detection. Sensitivity of LAMP assay is 100 times of conventional PCR technique. Although, both the LAMP and the PCR methods were capable of detecting ToLCBaV in infected tissues of tomato, the LAMP method would be more useful than the PCR method for detection of ToLCBaV infection in tomato plants because it is more rapid, simple and accurate method.",,"['Arutselvan, R.', 'Krishna Reddy, M.', 'Makeshkumar, T.']",,,,
,PMC,Retroviral host range extension is coupled with Env-activating mutations resulting in receptor-independent entry,http://dx.doi.org/10.1073/pnas.1704750114,PMC5495266,,,"The extent of virus transmission among individuals and species is generally determined by the presence of specific membrane-embedded virus receptors required for virus entry. Interaction of the viral envelope glycoprotein (Env) with a specific cellular receptor is the first and crucial step in determining host specificity. Using a well-established retroviral model—avian Rous sarcoma virus (RSV)—we analyzed changes in an RSV variant that had repeatedly been able to infect rodents. By envelope gene (env) sequencing, we identified eight mutations that do not match the already described mutations influencing the host range. Two of these mutations—one at the beginning (D32G) of the surface Env subunit (SU) and the other at the end of the fusion peptide region (L378S)—were found to be of critical importance, ensuring transmission to rodent, human, and chicken cells lacking the appropriate receptor. Furthermore, we carried out assays to examine the virus entry mechanism and concluded that these two mutations cause conformational changes in the Env variant and that these changes lead to an activated, or primed, state of Env (normally induced after Env interaction with the receptor). In summary, our results indicate that retroviral host range extension is caused by spontaneous Env activation, which circumvents the need for original cell receptor. This activation is, in turn, caused by mutations in various env regions.",,"['Lounková, Anna', 'Kosla, Jan', 'Přikryl, David', 'Štafl, Kryštof', 'Kučerová, Dana', 'Svoboda, Jan']",,,,
,PMC,Communicating infectious disease prevalence through graphics: results from an international survey,http://dx.doi.org/10.1016/j.vaccine.2017.05.048,PMC5660609,,,"BACKGROUND: Graphics are increasingly used to represent the spread of infectious diseases (e.g., influenza, Zika, Ebola); however, the impact of using graphics to adequately inform the general population is unknown. OBJECTIVE: To examine whether three ways of visually presenting data (heat map, dot map, or picto-trendline)—all depicting the same information regarding the spread of a hypothetical outbreak of influenza—influence intent to vaccinate, risk perception, and knowledge. DESIGN: Survey with participants randomized to receive a simulated news article accompanied by one of the three graphics that communicated prevalence of influenza and number of influenza-related deaths. SETTING: International online survey PARTICIPANTS: 16,510 adults living in 11 countries selected using stratified random sampling based on age and gender MEASUREMENTS: After reading the article and viewing the presented graphic, participants completed a survey that measured interest in vaccination, perceived risk of contracting disease, knowledge gained, interest in additional information about the disease, and perception of the graphic. RESULTS: Heat maps and picto-trendlines were evaluated more positively than dot maps. Heat maps were more effective than picto-trendlines and no different from dot maps at increasing interest in vaccination, perceived risk of contracting disease, and interest in additional information about the disease. Heat maps and picto-trendlines were more successful at conveying knowledge than dot maps. Overall, heat maps were the only graphic to be superior in every outcome. LIMITATIONS: Results are based on a hypothetical scenario CONCLUSION: Heat maps are a viable option to promote interest in and concern about infectious diseases.",,"['Fagerlin, Angela', 'Valley, Thomas S.', 'Scherer, Aaron M.', 'Knaus, Megan', 'Das, Enny', 'Zikmund-Fisher, Brian J.']",,,,
,PMC,Biomarker Profiling of Plasma Samples for Various Diseases Utilizing RANDOX Biochip Array Technology,http://dx.doi.org/10.23736/S0392-9590.17.03854-8,PMC6707717,,,"RANDOX Biochip Array Technology offers an efficient, cost-effective method of measuring multiple analytes on a large number of samples in biologic fluids. This innovative technology has proven extremely useful in the profiling of markers in a number of different disease states. Biochip arrays have also shown promise in clinical trials, offering rapid evaluation of multiple markers and circulating levels of the analyte with only a small sample. This biochip technology has broad applications in clinical, pharmaceutical, toxicological, immunologic and microbiologic areas. This technique offers parallel profiling and will have great value in personalized and precision medicine. The aim of this manuscript is to explore the recent and future utility of biochips for profiling marker levels in different diseased populations using RANDOX’s Biochip Array Technology.",,"['Saluk, Jennifer', 'Hoppensteadt, Debra', 'Syed, Danyel', 'Liles, Jeffrey', 'Abro, Schuharazad', 'Walborn, Amanda', 'Bansal, Vinod', 'Fareed, Jawed']",,,,
,PMC,Equine Arteritis Virus Has Specific Tropism for Stromal Cells and CD8(+) T and CD21(+) B Lymphocytes but Not for Glandular Epithelium at the Primary Site of Persistent Infection in the Stallion Reproductive Tract,http://dx.doi.org/10.1128/JVI.00418-17,PMC5469258,,,"Equine arteritis virus (EAV) has a global impact on the equine industry as the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of equids. A distinctive feature of EAV infection is that it establishes long-term persistent infection in 10 to 70% of infected stallions (carriers). In these stallions, EAV is detectable only in the reproductive tract, and viral persistence occurs despite the presence of high serum neutralizing antibody titers. Carrier stallions constitute the natural reservoir of the virus as they continuously shed EAV in their semen. Although the accessory sex glands have been implicated as the primary sites of EAV persistence, the viral host cell tropism and whether viral replication in carrier stallions occurs in the presence or absence of host inflammatory responses remain unknown. In this study, dual immunohistochemical and immunofluorescence techniques were employed to unequivocally demonstrate that the ampulla is the main EAV tissue reservoir rather than immunologically privileged tissues (i.e., testes). Furthermore, we demonstrate that EAV has specific tropism for stromal cells (fibrocytes and possibly tissue macrophages) and CD8(+) T and CD21(+) B lymphocytes but not glandular epithelium. Persistent EAV infection is associated with moderate, multifocal lymphoplasmacytic ampullitis comprising clusters of B (CD21(+)) lymphocytes and significant infiltration of T (CD3(+), CD4(+), CD8(+), and CD25(+)) lymphocytes, tissue macrophages, and dendritic cells (Iba-1(+) and CD83(+)), with a small number of tissue macrophages expressing CD163 and CD204 scavenger receptors. This study suggests that EAV employs complex immune evasion mechanisms that warrant further investigation. IMPORTANCE The major challenge for the worldwide control of EAV is that this virus has the distinctive ability to establish persistent infection in the stallion's reproductive tract as a mechanism to ensure its maintenance in equid populations. Therefore, the precise identification of tissue and cellular tropism of EAV is critical for understanding the molecular basis of viral persistence and for development of improved prophylactic or treatment strategies. This study significantly enhances our understanding of the EAV carrier state in stallions by unequivocally identifying the ampullae as the primary sites of viral persistence, combined with the fact that persistence involves continuous viral replication in fibrocytes (possibly including tissue macrophages) and T and B lymphocytes in the presence of detectable inflammatory responses, suggesting the involvement of complex viral mechanisms of immune evasion. Therefore, EAV persistence provides a powerful new natural animal model to study RNA virus persistence in the male reproductive tract.",,"['Carossino, Mariano', 'Loynachan, Alan T.', 'Canisso, Igor F.', 'Cook, R. Frank', 'Campos, Juliana R.', 'Nam, Bora', 'Go, Yun Young', 'Squires, Edward L.', 'Troedsson, Mats H. T.', 'Swerczek, Thomas', 'Del Piero, Fabio', 'Bailey, Ernest', 'Timoney, Peter J.', 'Balasuriya, Udeni B. R.']",,,,
,PMC,Simian Immunodeficiency Virus Targeting of CXCR3(+) CD4(+) T Cells in Secondary Lymphoid Organs Is Associated with Robust CXCL10 Expression in Monocyte/Macrophage Subsets,http://dx.doi.org/10.1128/JVI.00439-17,PMC5469254,,,"Glycosylation of Env defines pathogenic properties of simian immunodeficiency virus (SIV). We previously demonstrated that pathogenic SIVmac239 and a live-attenuated, quintuple deglycosylated Env mutant (Δ5G) virus target CD4(+) T cells residing in different tissues during acute infection. SIVmac239 and Δ5G preferentially infected distinct CD4(+) T cells in secondary lymphoid organs (SLOs) and within the lamina propria of the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323–9336, 2012, https://doi.org/10.1128/JVI.00948-12). Here, we studied the host responses relevant to SIV targeting of CXCR3(+) CCR5(+) CD4(+) T cells in SLOs. Genome-wide transcriptome analyses revealed that Th1-polarized inflammatory responses, defined by expression of CXCR3 chemokines, were distinctly induced in the SIVmac239-infected animals. Consistent with robust expression of CXCL10, CXCR3(+) T cells were depleted from blood in the SIVmac239-infected animals. We also discovered that elevation of CXCL10 expression in blood and SLOs was secondary to the induction of CD14(+) CD16(+) monocytes and MAC387(+) macrophages, respectively. Since the significantly higher levels of SIV infection in SLOs occurred with a massive accumulation of infiltrated MAC387(+) macrophages, T cells, dendritic cells (DCs), and residential macrophages near high endothelial venules, the results highlight critical roles of innate/inflammatory responses in SIVmac239 infection. Restricted infection in SLOs by Δ5G also suggests that glycosylation of Env modulates innate/inflammatory responses elicited by cells of monocyte/macrophage/DC lineages. IMPORTANCE We previously demonstrated that a pathogenic SIVmac239 virus and a live-attenuated, deglycosylated mutant Δ5G virus infected distinct CD4(+) T cell subsets in SLOs and the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323–9336, 2012, https://doi.org/10.1128/JVI.00948-12). Accordingly, infections with SIVmac239, but not with Δ5G, deplete CXCR3(+) CCR5(+) CD4(+) T (Th1) cells during the primary infection, thereby compromising the cellular immune response. Thus, we hypothesized that distinct host responses are elicited by the infections with two different viruses. We found that SIVmac239 induced distinctly higher levels of inflammatory Th1 responses than Δ5G. In particular, SIVmac239 infection elicited robust expression of CXCL10, a chemokine for CXCR3(+) cells, in CD14(+) CD16(+) monocytes and MAC387(+) macrophages recently infiltrated in SLOs. In contrast, Δ5G infection elicited only modest inflammatory responses. These results suggest that the glycosylation of Env modulates the inflammatory/Th1 responses through the monocyte/macrophage subsets and elicits marked differences in SIV infection and clinical outcomes.",,"['Fujino, Masayuki', 'Sato, Hirotaka', 'Okamura, Tomotaka', 'Uda, Akihiko', 'Takeda, Satoshi', 'Ahmed, Nursarat', 'Shichino, Shigeyuki', 'Shiino, Teiichiro', 'Saito, Yohei', 'Watanabe, Satoru', 'Sugimoto, Chie', 'Kuroda, Marcelo J.', 'Ato, Manabu', 'Nagai, Yoshiyuki', 'Izumo, Shuji', 'Matsushima, Kouji', 'Miyazawa, Masaaki', 'Ansari, Aftab A.', 'Villinger, Francois', 'Mori, Kazuyasu']",,,,
,PMC,"No Serologic Evidence of Middle East Respiratory Syndrome Coronavirus Infection Among Camel Farmers Exposed to Highly Seropositive Camel Herds: A Household Linked Study, Kenya, 2013",http://dx.doi.org/10.4269/ajtmh.16-0880,PMC5462565,,,"High seroprevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) among camels has been reported in Kenya and other countries in Africa. To date, the only report of MERS-CoV seropositivity among humans in Kenya is of two livestock keepers with no known contact with camels. We assessed whether persons exposed to seropositive camels at household level had serological evidence of infection. In 2013, 760 human and 879 camel sera were collected from 275 and 85 households respectively in Marsabit County. Data on human and animal demographics and type of contact with camels were collected. Human and camel sera were tested for anti-MERS-CoV IgG using a commercial enzyme-linked immunosorbent assay (ELISA) test. Human samples were confirmed by plaque reduction neutralization test (PRNT). Logistic regression was used to identify factors associated with seropositivity. The median age of persons sampled was 30 years (range: 5–90) and 50% were males. A quarter (197/760) of the participants reported having had contact with camels defined as milking, feeding, watering, slaughtering, or herding. Of the human sera, 18 (2.4%) were positive on ELISA but negative by PRNT. Of the camel sera, 791 (90%) were positive on ELISA. On univariate analysis, higher prevalence was observed in female and older camels over 4 years of age (P < 0.05). On multivariate analysis, only age remained significantly associated with increased odds of seropositivity. Despite high seroprevalence among camels, there was no serological confirmation of MERS-CoV infection among camel pastoralists in Marsabit County. The high seropositivity suggests that MERS-CoV or other closely related virus continues to circulate in camels and highlights ongoing potential for animal-to-human transmission.",,"['Munyua, Peninah', 'Corman, Victor Max', 'Bitek, Austine', 'Osoro, Eric', 'Meyer, Benjamin', 'Müller, Marcel A.', 'Lattwein, Erik', 'Thumbi, S. M.', 'Murithi, Rees', 'Widdowson, Marc-Alain', 'Drosten, Christian', 'Njenga, M. Kariuki']",,,,
,PMC,Reducing Uncertainty for Acute Febrile Illness in Resource-Limited Settings: The Current Diagnostic Landscape,http://dx.doi.org/10.4269/ajtmh.16-0667,PMC5462561,,,"Diagnosing the cause of acute febrile illness in resource-limited settings is important—to give the correct antimicrobials to patients who need them, to prevent unnecessary antimicrobial use, to detect emerging infectious diseases early, and to guide vaccine deployment. A variety of approaches are yielding more rapid and accurate tests that can detect more pathogens in a wider variety of settings. After decades of slow progress in diagnostics for acute febrile illness in resource-limited settings, a wave of converging advancements will enable clinicians in resource-limited settings to reduce uncertainty for the diagnosis of acute febrile illness.",,"['Robinson, Matthew L.', 'Manabe, Yukari C.']",,,,
,PMC,Male Infertility Is Responsible for Nearly Half of the Extinction Observed in the Mouse Collaborative Cross,http://dx.doi.org/10.1534/genetics.116.199596,PMC5499172,,,"The goal of the Collaborative Cross (CC) project was to generate and distribute over 1000 independent mouse recombinant inbred strains derived from eight inbred founders. With inbreeding nearly complete, we estimated the extinction rate among CC lines at a remarkable 95%, which is substantially higher than in the derivation of other mouse recombinant inbred populations. Here, we report genome-wide allele frequencies in 347 extinct CC lines. Contrary to expectations, autosomes had equal allelic contributions from the eight founders, but chromosome X had significantly lower allelic contributions from the two inbred founders with underrepresented subspecific origins (PWK/PhJ and CAST/EiJ). By comparing extinct CC lines to living CC strains, we conclude that a complex genetic architecture is driving extinction, and selection pressures are different on the autosomes and chromosome X. Male infertility played a large role in extinction as 47% of extinct lines had males that were infertile. Males from extinct lines had high variability in reproductive organ size, low sperm counts, low sperm motility, and a high rate of vacuolization of seminiferous tubules. We performed QTL mapping and identified nine genomic regions associated with male fertility and reproductive phenotypes. Many of the allelic effects in the QTL were driven by the two founders with underrepresented subspecific origins, including a QTL on chromosome X for infertility that was driven by the PWK/PhJ haplotype. We also performed the first example of cross validation using complementary CC resources to verify the effect of sperm curvilinear velocity from the PWK/PhJ haplotype on chromosome 2 in an independent population across multiple generations. While selection typically constrains the examination of reproductive traits toward the more fertile alleles, the CC extinct lines provided a unique opportunity to study the genetic architecture of fertility in a widely genetically variable population. We hypothesize that incompatibilities between alleles with different subspecific origins is a key driver of infertility. These results help clarify the factors that drove strain extinction in the CC, reveal the genetic regions associated with poor fertility in the CC, and serve as a resource to further study mammalian infertility.",,"['Shorter, John R.', 'Odet, Fanny', 'Aylor, David L.', 'Pan, Wenqi', 'Kao, Chia-Yu', 'Fu, Chen-Ping', 'Morgan, Andrew P.', 'Greenstein, Seth', 'Bell, Timothy A.', 'Stevans, Alicia M.', 'Feathers, Ryan W.', 'Patel, Sunny', 'Cates, Sarah E.', 'Shaw, Ginger D.', 'Miller, Darla R.', 'Chesler, Elissa J.', 'McMillian, Leonard', 'O’Brien, Deborah A.', 'de Villena, Fernando Pardo-Manuel']",,,,
,PMC,Potential applications and human biosafety of nanomaterials used in nanomedicine,http://dx.doi.org/10.1002/jat.3476,PMC6506719,,,"With the rapid development of nanotechnology, potential applications of nanomaterials in medicine have been widely researched in recent years. Nanomaterials themselves can be used as image agents or therapeutic drugs, and for drug and gene delivery, biological devices, nanoelectronic biosensors or molecular nanotechnology. As the composition, morphology, chemical properties, implant sites as well as potential applications become more and more complex, human biosafety of nanomaterials for clinical use has become a major concern. If nanoparticles accumulate in the human body or interact with the body molecules or chemical components, health risks may also occur. Accordingly, the unique chemical and physical properties, potential applications in medical fields, as well as human biosafety in clinical trials are reviewed in this study. Finally, this article tries to give some suggestions for future work in nanomedicine research.",,"['Su, Hong', 'Wang, Yafei', 'Gu, Yuanliang', 'Bowman, Linda', 'Zhao, Jinshun', 'Ding, Min']",,,,
,PMC,IRE-1α promotes viral infection by conferring resistance to apoptosis,http://dx.doi.org/10.1126/scisignal.aai7814,PMC5535312,,,"The unfolded protein response (UPR) is an ancient cellular pathway that detects and alleviates protein-folding stresses. The UPR components X-box binding protein 1 (XBP1) and inositol-requiring enzyme 1α (IRE1α) promote type I interferon (IFN) responses. Here, we found that Xbp1-deficient mouse embryonic fibroblasts and macrophages had impaired antiviral resistance. Unexpectedly, this was not because of a defect in type I IFN responses, but rather an inability of Xbp1-deficient cells to undergo viral-induced apoptosis. The ability to undergo apoptosis directly limited infection in WT cells. Xbp1-deficient cells were generally resistant to the intrinsic pathway of apoptosis through an indirect mechanism involving activation of the nuclease IRE1α. We observed an IRE1α-dependent reduction in the abundance of the pro-apoptotic microRNA miR-125a, and a corresponding increase in the amounts of the members of the anti-apoptotic Bcl2 family. The activation of IRE1α by the hepatitis C virus (HCV) protein NS4B in Xbp1-proficient cells also conferred apoptosis resistance and promoted viral replication. Furthermore, we found evidence of IRE1α activation and decreased miR-125a abundance in liver biopsies from patients infected with HCV compared to those in the livers of healthy controls. Our results reveal a pro-survival role for IRE1α in virally infected cells, and suggest a possible target for IFN-independent antiviral therapy.",,"['Fink, Susan L.', 'Jayewickreme, Teshika R.', 'Molony, Ryan D.', 'Iwawaki, Takao', 'Landis, Charles S.', 'Lindenbach, Brett D.', 'Iwasaki, Akiko']",,,,
,PMC,An RNAi-based high-throughput screening assay to identify small molecule inhibitors of hepatitis B virus replication,http://dx.doi.org/10.1074/jbc.M117.775155,PMC5535032,,,"Persistent or chronic infection with the hepatitis B virus (HBV) represents one of the most common viral diseases in humans. The hepatitis B virus deploys the hepatitis B virus X protein (HBx) as a suppressor of host defenses consisting of RNAi-based silencing of viral genes. Because of its critical role in countering host defenses, HBx represents an attractive target for antiviral drugs. Here, we developed and optimized a loss-of-function screening procedure, which identified a potential pharmacophore that abrogated HBx RNAi suppression activity. In a survey of 14,400 compounds in the Maybridge Screening Collection, we prioritized candidate compounds via high-throughput screening based on reversal of green fluorescent protein (GFP)–reported, RNAi-mediated silencing in a HepG2/GFP-shRNA RNAi sensor line. The screening yielded a pharmacologically active compound, N-(2,4-difluorophenyl)-N′-[3-(1H-imidazol-1-yl) propyl] thiourea (IR415), which blocked HBx-mediated RNAi suppression indicated by the GFP reporter assay. We also found that IR415 reversed the inhibitory effect of HBx protein on activity of the Dicer endoribonuclease. We further confirmed the results of the primary screen in IR415-treated, HBV-infected HepG2 cells, which exhibited a marked depletion of HBV core protein synthesis and down-regulation of pre-genomic HBV RNA. Using a molecular interaction analysis system, we confirmed that IR415 selectively targets HBx in a concentration-dependent manner. The screening assay presented here allows rapid and improved detection of small-molecule inhibitors of HBx and related viral proteins. The assay may therefore potentiate the development of next-generation RNAi pathway-based therapeutics and promises to accelerate our search for novel and effective drugs in antiviral research.",,"['Ghosh, Subhanita', 'Kaushik, Abhinav', 'Khurana, Sachin', 'Varshney, Aditi', 'Singh, Avishek Kumar', 'Dahiya, Pradeep', 'Thakur, Jitendra K.', 'Sarin, Shiv Kumar', 'Gupta, Dinesh', 'Malhotra, Pawan', 'Mukherjee, Sunil K.', 'Bhatnagar, Raj K.']",,,,
,PMC,Controlled and sustained delivery of siRNA/NPs from hydrogels expedites bone fracture healing,http://dx.doi.org/10.1016/j.biomaterials.2017.06.001,PMC5599180,,,"Despite great potential, delivery remains as the most significant barrier to the widespread use of siRNA therapeutics. siRNA has delivery limitations due to susceptibility to RNase degradation, low cellular uptake, and poor tissue-specific localization. Here, we report the development of a hybrid nanoparticle (NP)/hydrogel system that overcomes these challenges. Hydrogels provide localized and sustained delivery via controlled release of entrapped siRNA/NP complexes while NPs protect and enable efficient cytosolic accumulation of siRNA. To demonstrate therapeutic efficacy, regenerative siRNA against WW domain-containing E3 ubiquitin protein ligase 1 (Wwp1) complexed with NP were entrapped within poly(ethylene glycol) (PEG)-based hydrogels and implanted at sites of murine mid-diaphyseal femur fractures. Results showed localization of hydrogels and controlled release of siRNA/NPs at fractures for 28 days, a timeframe over which fracture healing occurs. siRNA/NP sustained delivery from hydrogels resulted in significant Wwp1 silencing at fracture callus compared to untreated controls. Fractures treated with siRNA/NP hydrogels exhibited accelerated bone formation and significantly increased biomechanical strength. This NP/hydrogel siRNA delivery system has outstanding therapeutic promise to augment fracture healing. Owing to the structural similarities of siRNA, the development of the hydrogel platform for in vivo siRNA delivery has myriad therapeutic possibilities in orthopaedics and beyond.",,"['Wang, Yuchen', 'Malcolm, Dominic W.', 'Benoit, Danielle S.W.']",,,,
,PMC,ProMED-mail: 22 years of digital surveillance of emerging infectious diseases,http://dx.doi.org/10.1093/inthealth/ihx014,PMC5881259,,,"ProMED-mail (ProMED) was launched in 1994 as an email service to identify unusual health events related to emerging and re-emerging infectious diseases and toxins affecting humans, animals and plants. It is used daily by public health leaders, government officials at all levels, physicians, veterinarians and other healthcare workers, researchers, private companies, journalists and the general public. Reports are produced and commentary provided by a global team of subject matter experts in a variety of fields including virology, parasitology, epidemiology, entomology, veterinary and plant disease specialists. ProMED operates 24 hours a day, 7 days a week and has over 83 000 subscribers, representing every country in the world. Additionally, ProMED disseminates information via its website and through social media channels such as Twitter and Facebook as well as through RSS feeds. Over the last 22 years, it has been the first to report on numerous major and minor disease outbreaks including SARS, MERS, Ebola and the early spread of Zika. ProMED is transparent, apolitical, open to all and free of charge, making it an important and longstanding contributor to global health surveillance.",,"['Carrion, Malwina', 'Madoff, Lawrence C.']",,,,
,PMC,Evolution Of Selective-Sequencing Approaches For Virus Discovery And Virome Analysis,http://dx.doi.org/10.1016/j.virusres.2017.06.005,PMC5819613,,,"Recent advances in sequencing technologies have transformed the field of virus discovery and virome analysis. Once, mostly confined to the traditional Sanger sequencing based individual virus discovery, is now entirely replaced by high throughput sequencing (HTS) based virus metagenomics that can be used to characterize the nature and composition of entire viromes. To better harness the potential of HTS for study of viromes, sample preparation methodologies used different refinements to exclude amplification of non-viral components that can overshadow low-titer viruses. These virus-sequence enrichment approaches mostly focused on the sample preparation methods, like enzymatic digestion of non-viral nucleic acids and size exclusion of non-viral constituents by column filtration, ultrafiltration or density centrifugation. However, recently an approach of virus-sequence enrichment called virome-capture sequencing, focused on the amplification or HTS library preparation stage, was shown to increase the ability of virome characterization. This new approach has the potential to further transform the field of virus discovery and virome analysis, but its technical complexity and sequence-dependence warrants further improvements. In this review we have listed the different methods, their applications and evolution, for selective sequencing based virome analysis and also the major refinements needed to harness the full potential of HTS for virome analysis.",,"['Kumar, Arvind', 'Murthy, Satyapramod', 'Kapoor, Amit']",,,,
,PMC,Invasive pneumococcal infection due to serotype 15A after the pneumococcal conjugate vaccine implementation in Turkey,http://dx.doi.org/10.1080/21645515.2017.1331802,PMC5557239,,,"Invasive pneumococcal infections among children are a serious public health problem in many countries, including Turkey. Pneumococcal conjugate vaccine has been included in Turkey's National Immunization Programme since 2009. We report the first two pediatric cases of invasive pneumococcal infection due to non-vaccine serotype 15A after pneumococcal conjugate vaccine implementation in Turkey. It is essential to monitor the countries’ own local seroepidemiologic data for detecting selective pressure of non-vaccine serotypes of S. pneumonia.",,"['Büyükcam, Ayşe', 'Güdücüoğlu, Hüseyin', 'Karaman, Kamuran', 'Gürbüz, Venhar', 'Aliyev, Emil', 'Kara, Ateş', 'Ceyhan, Mehmet']",,,,
,PMC,Isolationist Policies Threaten Public Health,http://dx.doi.org/10.2105/AJPH.2017.303779,PMC5425880,,,,,"['Coughlin, Christine Nero', 'Messenlehner, Adam']",,,,
,PMC,Biosecurity practices and causes of enteritis on Ontario meat rabbit farms,,PMC5432143,,,Infectious enterocolitis is a significant cause of mortality in meat rabbits. Disease risk is enhanced by intensive rearing practices and poor on-farm biosecurity. This investigation was undertaken in farmed meat rabbits during an Ontario-wide outbreak of enteritis with high mortality to determine the prevalence of causative agents. A survey evaluating on-farm biosecurity practices was also conducted to identify potential means of pathogen contamination and zoonotic risks. Gross and microscopic pathology evaluations combined with microbiologic testing were conducted on 95 rabbits over spring and winter months. Escherichia coli and Clostridium spiroforme were most commonly associated with enteritis in rabbits regardless of age or season and lesions were significantly more severe in mature does (P < 0.0001). The survey results demonstrated a lack of consistent on-farm biosecurity practices. The infectious nature of enteric disease of rabbits combined with poor biosecurity practices may contribute to disease transmission within and between farms.,,"['Kylie, Jennifer', 'Brash, Marina', 'Whiteman, Ashley', 'Tapscott, Brian', 'Slavic, Durda', 'Weese, J. Scott', 'Turner, Patricia V.']",,,,
,PMC,Special Issue: Infectious Disease Research: Animal Models and Risk Management,,PMC5482510,,,,,"['Villano, Jason S', 'Ogden, Bryan E']",,,,
,PMC,Persistent bovine viral diarrhea virus (BVDV) infection in cattle herds,,PMC5674437,,,"Bovine viral diarrhea virus (BVDV) is a significant pathogen associated with gastrointestinal, respiratory, and reproductive diseases of cattle worldwide. It causes continuous economic losses to the cattle industry primarily due to decreased reproductive performance. The ability of virus to cross the placenta during early pregnancy can result in the birth of persistently infected (PI) calves. Persistently infected animals are generally much more efficient transmitters of BVDV than transiently or acutely infected animals because they are capable of shedding large quantities of virus throughout their lives and are considered the primary reservoirs for BVDV. Due to the nature of viral infections, there is no treatment to fully cure an animal of a viral infection. All control programs which are in use in many countries of the world, mainly depend upon the detection of PI animals, eliminating them and preventing their return into the herds. Detection of PI animals at early stage, particularly soon after birth is of significant benefit to implement BVDV control programs. Available diagnostic tests such as virus isolation (VI), immunohistochemistry (IHC), Antigen-Capture ELISA (ACE), and reverse transcriptase polymerase chain reaction (RT-PCR) are used for detection of PI cattle. Each method to detect BVDV has advantages, disadvantages, and applicability for different diagnostic situations. The reliability of diagnostic tests is optimized by choosing the appropriate sampling strategy on the basis of animal age.",,"['Khodakaram-Tafti, A.', 'Farjanikish, GH.']",,,,
,PMC,Successful treatment of acute respiratory failure in a patient with pulmonary Mycobacterium abscessus infection accompanied by organizing pneumonia,http://dx.doi.org/10.21037/jtd.2017.05.51,PMC5506154,,,"Organizing pneumonia (OP) is an inflammatory lung disease characterized pathologically by the presence of buds of granulation tissue in the distal air spaces. There are numerous causes of OP including acute respiratory infections such as viral and bacterial infections. However, Mycobacterium abscessus (M. abscessus) has rarely been reported as a causative pathogen of OP. Here, we report a 67-year-old woman with rapidly progressive pulmonary M. abscessus infection who developed OP and acute respiratory failure (ARF). She was treated successfully with a corticosteroid and anti-mycobacterial therapy. Our observations suggest that pulmonary M. abscessus infection should be added to the list of infectious conditions associated with OP.",,"['Hong, Goohyeon', 'Kim, Doh Hyung', 'Kim, Youn Seup']",,,,
,PMC,South African guideline for the management of community-acquired pneumonia in adults,http://dx.doi.org/10.21037/jtd.2017.05.31,PMC5506119,,,,,"['Boyles, Tom H.', 'Brink, Adrian', 'Calligaro, Greg L.', 'Cohen, Cheryl', 'Dheda, Keertan', 'Maartens, Gary', 'Richards, Guy A.', 'van Zyl Smit, Richard', 'Smith, Clifford', 'Wasserman, Sean', 'Whitelaw, Andrew C.', 'Feldman, Charles', None, None]",,,,
,PMC,Evaluation of potential anti-toxoplasmosis efficiency of combined traditional herbs in a mouse model,http://dx.doi.org/10.1631/jzus.B1600316,PMC5482040,,,"Toxoplasma gondii is a worldwide spread protozoan and is able to infect almost all warm-blood animals. No effective drugs are available clinically on toxoplasmosis. Chinese traditional herbal medicines have provided remedies for many health problems. There exists a possibility that Chinese herbs may provide protection against T. gondii. This work aims to assess the protective efficacy of combined Chinese herbs against T. gondii. We screened five herbal medicines that have different pharmacological effects and combined them into a prescription according to the traditional Chinese medicine compatibility principle. The drug potential and protective efficacy were evaluated through a mouse model by determining the survival time, the parasite load in blood and tissues, the change of cell proportions in blood and histological detection. The results showed that the survival time of mice in the 500 mg Chinese herbs group and sulfadiazine group was significantly longer than that of the PBS control group. Also the parasite load in blood and tissues of 500 mg Chinese herbs and sulfadiazine groups was significantly lower than that of PBS group at 7 days post infection (dpi), which was in accordance with the result of histological detection. Monocyte and neutrophil of infected mice were remarkably increased while lymphocyte was dramatically decreased compared to that of blank group at 7 dpi. The results demonstrated that the 500 mg dosage of our Chinese herbs could slow down the replication of T. gondii and prolong the survival time of mice and could be considered as possible candidate drug against toxoplasmosis.",,"['Zhuo, Xun-hui', 'Sun, Hong-chao', 'Huang, Bin', 'Yu, Hai-jie', 'Shan, Ying', 'Du, Ai-fang']",,,,
,PMC,The Promise of Molecular Imaging in the Study and Treatment of Infectious Diseases,http://dx.doi.org/10.1007/s11307-017-1055-0,PMC5407939,,,"Infectious diseases are a major threat to humanity, and it is imperative that we develop imaging tools that aid in their study, facilitate diagnosis, and guide treatment. The alarming rise of highly virulent and multi-drug-resistant pathogens, their rapid spread leading to frequent global pandemics, fears of bioterrorism, and continued life-threatening nosocomial infections in hospitals remain as major challenges to health care in the USA and worldwide. Early diagnosis and rapid monitoring are essential for appropriate management and control of infections. Tomographic molecular imaging enables rapid, noninvasive visualization, localization, and monitoring of molecular processes deep within the body and offers several advantages over traditional tools used for the study of infectious diseases. Noninvasive, longitudinal assessments could streamline animal studies, allow unique insights into disease pathogenesis, and expedite clinical translation of new therapeutics. Since molecular imaging is already in common use in the clinic, it could also become a valuable tool for clinical studies, for patient care, for public health, and for enabling precision medicine for infectious diseases.",,"Jain, Sanjay K.",,,,
,PMC,Detection of diverse viruses in alimentary specimens of bats in Macau,http://dx.doi.org/10.1007/s12250-017-3976-9,PMC6598931,,,"Bats carry a variety of viruses, and some of them cause public health problems. Macau, which is famous for its gambling industry, has a complex population structure. The globalization in such an international metropolis has enhanced the chance of disease transmission. Therefore, surveillance of zoonotic viruses is necessary for the early warning of potential emerging infectious diseases. Here, we report the first surveillance of bat viruses in Macau. In this study, we collected 1004 samples involving 10 bat species from 7 sites from April 2015 to May 2016, and examined the presence of viruses using nucleic acid-based methods. Coronaviruses, adenoviruses and paramyxoviruses were detected in these samples, with a high prevalence of coronaviruses. While, none was positive for hepatitis A virus, hepatitis E virus or hantavirus. Co-infections are not common in those bat species, but coronavirus HKU6 and adenovirus can be found commonly occurred in Myotis ricketti.",,"['Liang, Jie', 'Yang, Xing-Lou', 'Li, Bei', 'Liu, Qi', 'Zhang, Qin', 'Liu, Hui', 'Kan, Hon-Pio', 'Wong, Kai-Chin', 'Chek, Si-Nga', 'He, Xiangyang', 'Peng, Xingwen', 'Shi, Zheng-Li', 'Wu, Yi', 'Zhang, Libiao']",,,,
,PMC,Microtubule-assisted altered trafficking of astrocytic gap junction protein connexin 43 is associated with depletion of connexin 47 during mouse hepatitis virus infection,http://dx.doi.org/10.1074/jbc.M117.786491,PMC5592656,,,"Gap junctions (GJs) are important for maintenance of CNS homeostasis. GJ proteins, connexin 43 (Cx43) and connexin 47 (Cx47), play a crucial role in production and maintenance of CNS myelin. Cx43 is mainly expressed by astrocytes in the CNS and forms gap junction intercellular communications between astrocytes-astrocytes (Cx43–Cx43) and between astrocytes-oligodendrocytes (Cx43–Cx47). Mutations of these connexin (Cx) proteins cause dysmyelinating diseases in humans. Previously, it has been shown that Cx43 localization and expression is altered due to mouse hepatitis virus (MHV)-A59 infection both in vivo and in vitro; however, its mechanism and association with loss of myelin protein was not elaborated. Thus, we explored potential mechanisms by which MHV-A59 infection alters Cx43 localization and examined the effects of viral infection on Cx47 expression and its association with loss of the myelin marker proteolipid protein. Immunofluorescence and total internal reflection fluorescence microscopy confirmed that MHV-A59 used microtubules (MTs) as a conduit to reach the cell surface and restricted MT-mediated Cx43 delivery to the cell membrane. Co-immunoprecipitation experiments demonstrated that Cx43–β-tubulin molecular interaction was depleted due to protein–protein interaction between viral particles and MTs. During acute MHV-A59 infection, oligodendrocytic Cx47, which is mainly stabilized by Cx43 in vivo, was down-regulated, and its characteristic staining remained disrupted even at chronic phase. The loss of Cx47 was associated with loss of proteolipid protein at the chronic stage of MHV-A59 infection.",,"['Basu, Rahul', 'Bose, Abhishek', 'Thomas, Deepthi', 'Das Sarma, Jayasri']",,,,
,PMC,Viral Pathogen Detection by Metagenomics and Pan-Viral Group Polymerase Chain Reaction in Children With Pneumonia Lacking Identifiable Etiology,http://dx.doi.org/10.1093/infdis/jix148,PMC5565793,,,"BACKGROUND. Community-acquired pneumonia (CAP) is a leading cause of pediatric hospitalization. Pathogen identification fails in approximately 20% of children but is critical for optimal treatment and prevention of hospital-acquired infections. We used two broad-spectrum detection strategies to identify pathogens in test-negative children with CAP and asymptomatic controls. METHODS. Nasopharyngeal/oropharyngeal (NP/OP) swabs from 70 children <5 years with CAP of unknown etiology and 90 asymptomatic controls were tested by next-generation sequencing (RNA-seq) and pan viral group (PVG) PCR for 19 viral families. Association of viruses with CAP was assessed by adjusted odds ratios (aOR) and 95% confidence intervals controlling for season and age group. RESULTS. RNA-seq/PVG PCR detected previously missed, putative pathogens in 34% of patients. Putative viral pathogens included human parainfluenza virus 4 (aOR 9.3, P = .12), human bocavirus (aOR 9.1, P < .01), Coxsackieviruses (aOR 5.1, P = .09), rhinovirus A (aOR 3.5, P = .34), and rhinovirus C (aOR 2.9, P = .57). RNA-seq was more sensitive for RNA viruses whereas PVG PCR detected more DNA viruses. CONCLUSIONS. RNA-seq and PVG PCR identified additional viruses, some known to be pathogenic, in NP/OP specimens from one-third of children hospitalized with CAP without a previously identified etiology. Both broad-range methods could be useful tools in future epidemiologic and diagnostic studies.",,"['Schlaberg, Robert', 'Queen, Krista', 'Simmon, Keith', 'Tardif, Keith', 'Stockmann, Chris', 'Flygare, Steven', 'Kennedy, Brett', 'Voelkerding, Karl', 'Bramley, Anna', 'Zhang, Jing', 'Eilbeck, Karen', 'Yandell, Mark', 'Jain, Seema', 'Pavia, Andrew T.', 'Tong, Suxiang', 'Ampofo, Krow']",,,,
,PMC,"MERS‐CoV papain-like protease (PL(pro)): expression, purification, and spectroscopic/thermodynamic characterization",http://dx.doi.org/10.1007/s13205-017-0744-3,PMC5449288,,,"Within a decade, MERS-CoV emerged with nearly four times higher case fatality rate than an earlier outbreak of SARS-CoV and spread out in 27 countries in short span of time. As an emerging virus, combating it requires an in-depth understanding of its molecular machinery. Therefore, conformational characterization studies of coronavirus proteins are necessary to advance our knowledge of the matter for the development of antiviral therapies. In this study, MERS-CoV papain-like protease (PL(pro)) was recombinantly expressed and purified. Thermal folding pathway and thermodynamic properties were characterized using dynamic multimode spectroscopy (DMS) and thermal shift assay. DMS study showed that the PL(pro) undergoes a single thermal transition and follows a pathway of two-state folding with T (m) and van’t Hoff enthalpy values of 54.4 ± 0.1 °C and 317.1 ± 3.9 kJ/mol, respectively. An orthogonal technique based on intrinsic tryptophan fluorescence also showed that MERS-CoV PL(pro) undergoes a single thermal transition and unfolds via a pathway of two-state folding with a T (m) value of 51.4 °C. Our findings provide significant understandings of the thermodynamic and structural properties of MERS-CoV PL(pro).",,"['Malik, Ajamaluddin', 'Alsenaidy, Mohammad A.']",,,,
,PMC,"The Use of Xenosurveillance to Detect Human Bacteria, Parasites, and Viruses in Mosquito Bloodmeals",http://dx.doi.org/10.4269/ajtmh.17-0063,PMC5544101,,,"Infectious disease surveillance is hindered by several factors, including limited infrastructure and geographic isolation of many resource-poor regions. In addition, the complexities of sample acquisition, processing, and analysis, even in developed regions, can be rate limiting. Therefore, new strategies to survey human populations for emerging pathogens are necessary. Xenosurveillance is a method that utilizes mosquitoes as sampling devices to search for genetic signatures of pathogens in vertebrates. Previously we demonstrated that xenosurveillance can detect viral RNA in both laboratory and field settings. However, its ability to detect bacteria and parasites remains to be assessed. Accordingly, we fed Anopheles gambiae mosquitoes blood that contained Trypanosoma brucei gambiense and Bacillus anthracis. In addition, we determined whether two additional emerging viruses, Middle East Respiratory Syndrome Coronavirus and Zika virus could be detected by this method. Pathogen-specific real-time reverse transcription polymerase chain reaction was used to evaluate the sensitivity of xenosurveillance across multiple pathogen taxa and over time. We detected RNA from all pathogens at clinically relevant concentrations from mosquitoes processed up to 1 day postbloodfeeding. These results demonstrate that xenosurveillance may be used as a tool to expand surveillance for viral, parasitic, and bacterial pathogens in resource-limited areas.",,"['Fauver, Joseph R.', 'Gendernalik, Alex', 'Weger-Lucarelli, James', 'Grubaugh, Nathan D.', 'Brackney, Doug E.', 'Foy, Brian D.', 'Ebel, Gregory D.']",,,,
,PMC,Prolonged Shedding of Human Coronavirus in Hematopoietic Cell Transplant Recipients: Risk Factors and Viral Genome Evolution,http://dx.doi.org/10.1093/infdis/jix264,PMC5853311,,,"BACKGROUND: Recent data suggest that human coronavirus (HCoV) pneumonia is associated with significant mortality in hematopoietic cell transplant (HCT) recipients. Investigation of risk factors for prolonged shedding and intrahost genome evolution may provide critical information for development of novel therapeutics. METHODS: We retrospectively reviewed HCT recipients with HCoV detected in nasal samples by polymerase chain reaction (PCR). HCoV strains were identified using strain-specific PCR. Shedding duration was defined as time between first positive and first negative sample. Logistic regression analyses were performed to evaluate factors for prolonged shedding (≥21 days). Metagenomic next-generation sequencing (mNGS) was conducted when ≥4 samples with cycle threshold values of <28 were available. RESULTS: Seventeen of 44 patients had prolonged shedding. Among 31 available samples, 35% were OC43, 32% were NL63, 19% were HKU1, and 13% were 229E; median shedding duration was similar between strains (P = .79). Bivariable logistic regression analyses suggested that high viral load, receipt of high-dose steroids, and myeloablative conditioning were associated with prolonged shedding. mNGS among 5 subjects showed single-nucleotide polymorphisms from OC43 and NL63 starting 1 month following onset of shedding. CONCLUSIONS: High viral load, high-dose steroids, and myeloablative conditioning were associated with prolonged shedding of HCoV in HCT recipients. Genome changes were consistent with the expected molecular clock of HCoV.",,"['Ogimi, Chikara', 'Greninger, Alexander L', 'Waghmare, Alpana A', 'Kuypers, Jane M', 'Shean, Ryan C', 'Xie, Hu', 'Leisenring, Wendy M', 'Stevens-Ayers, Terry L', 'Jerome, Keith R', 'Englund, Janet A', 'Boeckh, Michael']",,,,
,PMC,Giant Reverse Transcriptase-Encoding Transposable Elements at Telomeres,http://dx.doi.org/10.1093/molbev/msx159,PMC5850863,,,"Transposable elements are omnipresent in eukaryotic genomes and have a profound impact on chromosome structure, function and evolution. Their structural and functional diversity is thought to be reasonably well-understood, especially in retroelements, which transpose via an RNA intermediate copied into cDNA by the element-encoded reverse transcriptase, and are characterized by a compact structure. Here, we report a novel type of expandable eukaryotic retroelements, which we call Terminons. These elements can attach to G-rich telomeric repeat overhangs at the chromosome ends, in a process apparently facilitated by complementary C-rich repeats at the 3′-end of the RNA template immediately adjacent to a hammerhead ribozyme motif. Terminon units, which can exceed 40 kb in length, display an unusually complex and diverse structure, and can form very long chains, with host genes often captured between units. As the principal polymerizing component, Terminons contain Athena reverse transcriptases previously described in bdelloid rotifers and belonging to the enigmatic group of Penelope-like elements, but can additionally accumulate multiple cooriented ORFs, including DEDDy 3′-exonucleases, GDSL esterases/lipases, GIY-YIG-like endonucleases, rolling-circle replication initiator (Rep) proteins, and putatively structural ORFs with coiled-coil motifs and transmembrane domains. The extraordinary length and complexity of Terminons and the high degree of interfamily variability in their ORF content challenge the current views on the structural organization of eukaryotic retroelements, and highlight their possible connections with the viral world and the implications for the elevated frequency of gene transfer.",,"['Arkhipova, Irina R.', 'Yushenova, Irina A.', 'Rodriguez, Fernando']",,,,
,PMC,Pathways to zoonotic spillover,http://dx.doi.org/10.1038/nrmicro.2017.45,PMC5791534,,,"Zoonotic spillover, which is the transmission of a pathogen from a vertebrate animal to a human, presents a global public health burden but is a poorly understood phenomenon. Zoonotic spillover requires several factors to align, including the ecological, epidemiological and behavioural determinants of pathogen exposure, and the within-human factors that affect susceptibility to infection. In this Opinion article, we propose a synthetic framework for animal-to-human transmission that integrates the relevant mechanisms. This framework reveals that all zoonotic pathogens must overcome a hierarchical series of barriers to cause spillover infections in humans. Understanding how these barriers are functionally and quantitatively linked, and how they interact in space and time, will substantially improve our ability to predict or prevent spillover events. This work provides a foundation for transdisciplinary investigation of spillover and synthetic theory on zoonotic transmission.",,"['Plowright, Raina K.', 'Parrish, Colin R.', 'McCallum, Hamish', 'Hudson, Peter J.', 'Ko, Albert I.', 'Graham, Andrea L.', 'Lloyd-Smith, James O.']",,,,
,PMC,Density of Upper Respiratory Colonization With Streptococcus pneumoniae and Its Role in the Diagnosis of Pneumococcal Pneumonia Among Children Aged <5 Years in the PERCH Study,http://dx.doi.org/10.1093/cid/cix100,PMC5850437,,,"BACKGROUND: Previous studies suggested an association between upper airway pneumococcal colonization density and pneumococcal pneumonia, but data in children are limited. Using data from the Pneumonia Etiology Research for Child Health (PERCH) study, we assessed this potential association. METHODS: PERCH is a case-control study in 7 countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. Cases were children aged 1–59 months hospitalized with World Health Organization–defined severe or very severe pneumonia. Controls were randomly selected from the community. Microbiologically confirmed pneumococcal pneumonia (MCPP) was confirmed by detection of pneumococcus in a relevant normally sterile body fluid. Colonization density was calculated with quantitative polymerase chain reaction analysis of nasopharyngeal/oropharyngeal specimens. RESULTS: Median colonization density among 56 cases with MCPP (MCPP cases; 17.28 × 10(6) copies/mL) exceeded that of cases without MCPP (non-MCPP cases; 0.75 × 10(6)) and controls (0.60 × 10(6)) (each P < .001). The optimal density for discriminating MCPP cases from controls using the Youden index was >6.9 log(10) copies/mL; overall, the sensitivity was 64% and the specificity 92%, with variable performance by site. The threshold was lower (≥4.4 log(10) copies/mL) when MCPP cases were distinguished from controls who received antibiotics before specimen collection. Among the 4035 non-MCPP cases, 500 (12%) had pneumococcal colonization density >6.9 log(10) copies/mL; above this cutoff was associated with alveolar consolidation at chest radiography, very severe pneumonia, oxygen saturation <92%, C-reactive protein ≥40 mg/L, and lack of antibiotic pretreatment (all P< .001). CONCLUSIONS: Pneumococcal colonization density >6.9 log(10) copies/mL was strongly associated with MCPP and could be used to improve estimates of pneumococcal pneumonia prevalence in childhood pneumonia studies. Our findings do not support its use for individual diagnosis in a clinical setting.",,"['Baggett, Henry C', 'Watson, Nora L', 'Deloria Knoll, Maria', 'Brooks, W Abdullah', 'Feikin, Daniel R', 'Hammitt, Laura L', 'Howie, Stephen R C', 'Kotloff, Karen L', 'Levine, Orin S', 'Madhi, Shabir A', 'Murdoch, David R', 'Scott, J Anthony G', 'Thea, Donald M', 'Antonio, Martin', 'Awori, Juliet O', 'Baillie, Vicky L', 'DeLuca, Andrea N', 'Driscoll, Amanda J', 'Duncan, Julie', 'Ebruke, Bernard E', 'Goswami, Doli', 'Higdon, Melissa M', 'Karron, Ruth A', 'Moore, David P', 'Morpeth, Susan C', 'Mulindwa, Justin M', 'Park, Daniel E', 'Paveenkittiporn, Wantana', 'Piralam, Barameht', 'Prosperi, Christine', 'Sow, Samba O', 'Tapia, Milagritos D', 'Zaman, Khalequ', 'Zeger, Scott L', 'O’Brien, Katherine L', None]",,,,
,PMC,Neural Immunoglobulin Superfamily Interaction Networks,http://dx.doi.org/10.1016/j.conb.2017.05.010,PMC5554755,,,"The immunoglobulin superfamily (IgSF) encompasses hundreds of cell surface proteins containing multiple immunoglobulin-like (Ig) domains. Among these are neural IgCAMs, which are cell adhesion molecules that mediate interactions between cells in the nervous system. IgCAMs in some vertebrate IgSF subfamilies bind to each other homophilically and heterophilically, forming small interaction networks. In Drosophila, a global ‘interactome’ screen identified two larger networks in which proteins in one IgSF subfamily selectively interact with proteins in a different subfamily. One of these networks, the ‘Dpr-ome’, includes 30 IgSF proteins, each of which is expressed in a unique subset of neurons. Recent evidence shows that one interacting protein pair within the Dpr-ome network is required for development of the brain and neuromuscular system.",,"['Zinn, Kai', 'Özkan, Engin']",,,,
,PMC,"Group A Rotaviruses in Chinese Bats: Genetic Composition, Serology, and Evidence for Bat-to-Human Transmission and Reassortment",http://dx.doi.org/10.1128/JVI.02493-16,PMC5446661,,,"Bats are natural reservoirs for many pathogenic viruses, and increasing evidence supports the notion that bats can also harbor group A rotaviruses (RVAs), important causative agents of diarrhea in children and young animals. Currently, 8 RVA strains possessing completely novel genotype constellations or genotypes possibly originating from other mammals have been identified from African and Chinese bats. However, all the data were mainly based on detection of RVA RNA, present only during acute infections, which does not permit assessment of the true exposure of a bat population to RVA. To systematically investigate the genetic diversity of RVAs, 547 bat anal swabs or gut samples along with 448 bat sera were collected from five South Chinese provinces. Specific reverse transcription-PCR (RT-PCR) screening found four RVA strains. Strain GLRL1 possessed a completely novel genotype constellation, whereas the other three possessed a constellation consistent with the MSLH14-like genotype, a newly characterized group of viruses widely prevalent in Chinese insectivorous bats. Among the latter, strain LZHP2 provided strong evidence of cross-species transmission of RVAs from bats to humans, whereas strains YSSK5 and BSTM70 were likely reassortants between typical MSLH14-like RVAs and human RVAs. RVA-specific antibodies were detected in 10.7% (48/448) of bat sera by an indirect immunofluorescence assay (IIFA). Bats in Guangxi and Yunnan had a higher RVA-specific antibody prevalence than those from Fujian and Zhejiang provinces. These observations provide evidence for cross-species transmission of MSLH14-like bat RVAs to humans, highlighting the impact of bats as reservoirs of RVAs on public health. IMPORTANCE Bat viruses, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), Ebola, Hendra, and Nipah viruses, are important pathogens causing outbreaks of severe emerging infectious diseases. However, little is known about bat viruses capable of causing gastroenteritis in humans, even though 8 group A viruses (RVAs) have been identified from bats so far. In this study, another 4 RVA strains were identified, with one providing strong evidence for zoonotic transmission from bats to humans. Serological investigation has also indicated that RVA infection in bats is far more prevalent than expected based on the detection of viral RNA.",,"['He, Biao', 'Huang, Xiaohong', 'Zhang, Fuqiang', 'Tan, Weilong', 'Matthijnssens, Jelle', 'Qin, Shaomin', 'Xu, Lin', 'Zhao, Zihan', ""Yang, Ling'en"", 'Wang, Quanxi', 'Hu, Tingsong', 'Bao, Xiaolei', 'Wu, Jianmin', 'Tu, Changchun']",,,,
,PMC,Overactive Epidermal Growth Factor Receptor Signaling Leads to Increased Fibrosis after Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/JVI.00182-17,PMC5446658,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic respiratory virus that causes morbidity and mortality in humans. After infection with SARS-CoV, the acute lung injury caused by the virus must be repaired to regain lung function. A dysregulation in this wound healing process leads to fibrosis. Many survivors of SARS-CoV infection develop pulmonary fibrosis (PF), with higher prevalence in older patients. Using mouse models of SARS-CoV pathogenesis, we have identified that the wound repair pathway, controlled by the epidermal growth factor receptor (EGFR), is critical to recovery from SARS-CoV-induced tissue damage. In mice with constitutively active EGFR [EGFR(DSK5) mice], we find that SARS-CoV infection causes enhanced lung disease. Importantly, we show that during infection, the EGFR ligands amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) are upregulated, and exogenous addition of these ligands during infection leads to enhanced lung disease and altered wound healing dynamics. Our data demonstrate a key role of EGFR in the host response to SARS-CoV and how it may be implicated in lung disease induced by other highly pathogenic respiratory viruses. IMPORTANCE PF has many causative triggers, including severe respiratory viruses such as SARS-CoV. Currently there are no treatments to prevent the onset or limit the progression of PF, and the molecular pathways underlying the development of PF are not well understood. In this study, we identified a role for the balanced control of EGFR signaling as a key factor in progression to PF. These data demonstrate that therapeutic treatment modulating EGFR activation could protect against PF development caused by severe respiratory virus infection.",,"['Venkataraman, Thiagarajan', 'Coleman, Christopher M.', 'Frieman, Matthew B.']",,,,
,PMC,Cell Attachment Domains of the Porcine Epidemic Diarrhea Virus Spike Protein Are Key Targets of Neutralizing Antibodies,http://dx.doi.org/10.1128/JVI.00273-17,PMC5446644,,,"Porcine epidemic diarrhea virus (PEDV) causes enteric disease in pigs, resulting in significant economic losses to the swine industry worldwide. Current vaccination approaches against this emerging coronavirus are only partially effective, though natural infection protects pigs against reinfection and provides lactogenic immunity to suckling piglets. The viral spike (S) glycoprotein, responsible for receptor binding and cell entry, is the major target for neutralizing antibodies. However, knowledge of antibody epitopes, their nature and location in the spike structure, and the mechanisms by which the antibodies interfere with infection is scarce. Here we describe the generation and characterization of 10 neutralizing and nonneutralizing mouse monoclonal antibodies raised against the S1 receptor binding subunit of the S protein. By expression of different S1 protein fragments, six antibody epitope classes distributed over the five structural domains of the S1 subunit were identified. Characterization of antibodies for cross-reactivity and cross-neutralization revealed antigenic differences among PEDV strains. The epitopes of potent neutralizing antibodies segregated into two epitope classes and mapped within the N-terminal sialic acid binding domain and in the more C-terminal receptor binding domain. Antibody neutralization escape mutants displayed single amino acid substitutions that impaired antibody binding and neutralization and defined the locations of the epitopes. Our observations picture the antibody epitope landscape of the PEDV S1 subunit and reveal that its cell attachment domains are key targets of neutralizing antibodies. IMPORTANCE Porcine epidemic diarrhea virus (PEDV), an emerging porcine coronavirus, causes an economically important enteric disease in pigs. Effective PEDV vaccines for disease control are currently lacking. The spike (S) glycoprotein on the virion surface is the key player in virus cell entry and, therefore, the main target of neutralizing antibodies. To understand the antigenic landscape of the PEDV spike protein, we developed monoclonal antibodies against the spike protein's S1 receptor binding region and characterized their epitopes, neutralizing activity, and cross-reactivity toward multiple PEDV strains. Epitopes of antibodies segregated into six epitope classes dispersed over the multidomain S1 structure. Monoclonal antibodies revealed antigenic variability in B-cell epitopes between PEDV strains. The epitopes of neutralizing antibodies mapped to two distinct domains in S1 that are involved in binding to carbohydrate and proteinaceous cell surface molecules, respectively, indicating the importance of these cell attachment sites on the PEDV spike protein in eliciting a protective humoral immune response.",,"['Li, Chunhua', 'Li, Wentao', 'Lucio de Esesarte, Eduardo', 'Guo, Hongbo', 'van den Elzen, Paul', 'Aarts, Eduard', 'van den Born, Erwin', 'Rottier, Peter J. M.', 'Bosch, Berend-Jan']",,,,
,PMC,Quantitative Proteomic Analysis of Mosquito C6/36 Cells Reveals Host Proteins Involved in Zika Virus Infection,http://dx.doi.org/10.1128/JVI.00554-17,PMC5446628,,,"Zika virus (ZIKV) is an emerging arbovirus belonging to the genus Flavivirus of the family Flaviviridae. During replication processes, flavivirus manipulates host cell systems to facilitate its replication, while the host cells activate antiviral responses. Identification of host proteins involved in the flavivirus replication process may lead to the discovery of antiviral targets. The mosquitoes Aedes aegypti and Aedes albopictus are epidemiologically important vectors for ZIKV, and effective restrictions of ZIKV replication in mosquitoes will be vital in controlling the spread of virus. In this study, an iTRAQ-based quantitative proteomic analysis of ZIKV-infected Aedes albopictus C6/36 cells was performed to investigate host proteins involved in the ZIKV infection process. A total of 3,544 host proteins were quantified, with 200 being differentially regulated, among which CHCHD2 can be upregulated by ZIKV infection in both mosquito C6/36 and human HeLa cells. Our further study indicated that CHCHD2 can promote ZIKV replication and inhibit beta interferon (IFN-β) production in HeLa cells, suggesting that ZIKV infection may upregulate CHCHD2 to inhibit IFN-I production and thus promote virus replication. Bioinformatics analysis of regulated host proteins highlighted several ZIKV infection-regulated biological processes. Further study indicated that the ubiquitin proteasome system (UPS) plays roles in the ZIKV entry process and that an FDA-approved inhibitor of the 20S proteasome, bortezomib, can inhibit ZIKV infection in vivo. Our study illustrated how host cells respond to ZIKV infection and also provided a candidate drug for the control of ZIKV infection in mosquitoes and treatment of ZIKV infection in patients. IMPORTANCE ZIKV infection poses great threats to human health, and there is no FDA-approved drug available for the treatment of ZIKV infection. During replication, ZIKV manipulates host cell systems to facilitate its replication, while host cells activate antiviral responses. Identification of host proteins involved in the ZIKV replication process may lead to the discovery of antiviral targets. In this study, the first quantitative proteomic analysis of ZIKV-infected cells was performed to investigate host proteins involved in the ZIKV replication process. Bioinformatics analysis highlighted several ZIKV infection-regulated biological processes. Further study indicated that the ubiquitin proteasome system (UPS) plays roles in the ZIKV entry process and that an FDA-approved inhibitor of the UPS, bortezomib, can inhibit ZIKV infection in vivo. Our study not only illustrated how host cells respond to ZIKV infection but also provided a candidate drug for the control of ZIKV infection in mosquitoes and treatment of ZIKV infection in patients.",,"['Xin, Qi-Lin', 'Deng, Cheng-Lin', 'Chen, Xi', 'Wang, Jun', 'Wang, Shao-Bo', 'Wang, Wei', 'Deng, Fei', 'Zhang, Bo', 'Xiao, Gengfu', 'Zhang, Lei-Ke']",,,,
,PMC,Sensitive Diagnostics Confirm That Influenza C is an Uncommon Cause of Medically Attended Respiratory Illness in Adults,http://dx.doi.org/10.1093/cid/cix471,PMC5850529,,,"Among 4200 adults who presented with acute respiratory symptoms at a variety of medical practice settings (November 2006 through May 2012), only 13 (0.3%) nasal/throat swabs were positive for influenza C. Influenza C was rarely associated with medical care visits in adults.",,"['Nesmith, Natalie', 'Williams, John V', 'Johnson, Monika', 'Zhu, Yuwei', 'Griffin, Marie', 'Talbot, H Keipp']",,,,
,PMC,Variability in viral pathogenesis: modeling the dynamic of acute and persistent infections,http://dx.doi.org/10.1016/j.coviro.2017.05.001,PMC5695700,,,"Virus infection often results in diverse outcomes. This variability of virus pathogenesis is not well understood. Here we revise theoretical arguments to further our understanding of factors controlling infection and its severity. We propose that variability in these factors results in different clinical outcomes, which ultimately ensure virus reproduction.",,"['Lidsky, Peter V.', 'Andino, Raul', 'Rouzine, Igor M.']",,,,
,PMC,The Comparative Effectiveness of Noninvasive and Invasive Ventilation in Patients with Pneumonia,http://dx.doi.org/10.1016/j.jcrc.2017.05.023,PMC5700851,,,"PURPOSE: To compare the outcomes of patients hospitalized with pneumonia treated with noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV). MATERIALS AND METHODS: Using the HealthFactsmultihospital electronic medical record database, we included patients hospitalized with a diagnosis of pneumonia and treated with NIV or IMV. We developed a propensity model for receipt of initial NIV and assessed the outcomes in a propensity-matched cohort, and though covariate adjusted and propensity score weighted models. RESULTS: Among 3971 ventilated patients, 1109 (27.9%) were initially treated with NIV. Patients treated with NIV were older, had lower acuity of illness score, and were more likely to have congestive heart failure andchronic pulmonary disease. Mortality was 15.8%, 29.8% and 25.9.0% among patients treated with initial NIV, initial IMV and among those with NIV failure. In the propensity matched analysis, the risk of death was lower in patients treated with NIV (relative risk: 0.71, 95% CI: 0.59–0.85). Subgroup analysis showed that NIV was beneficial among patients with cardiopulmonary comorbidities (relative risk 0.59, 95% CI: 0.47–0.75) but not in those without (relative risk 0.96, 95% CI: 0.74–0.1.25)NIV failure was significantly (p=0.002) more common in patients without cardiopulmonary conditions (21.3%) compared to those with these conditions (13.8%). CONCLUSIONS: Initial NIV was associated with better survival among the subgroup of patients hospitalized with pneumonia who had COPD or heart failure. Patients who failed NIV had high in-hospital mortality, emphasizing the importance of careful patient selection monitoring when managing severe pneumonia with NIV.",,"['Stefan, Mihaela S.', 'Priya, Aruna', 'Pekow, Penelope S', 'Lagu, Tara', 'Steingrub, Jay', 'Hill, Nicholas', 'Nathanson, Brian H.', 'Lindenauer, Peter K']",,,,
,PMC,PNAS Plus Significance Statements,http://dx.doi.org/10.1073/pnas.ss11421,PMC5448180,,,,,,,,,
,PMC,Phase-Separated Liposomes Enhance the Efficiency of Macromolecular Delivery to the Cellular Cytoplasm,http://dx.doi.org/10.1007/s12195-017-0489-4,PMC5665383,,,"INTRODUCTION: From viruses to organelles, fusion of biological membranes is used by diverse biological systems to deliver macromolecules across membrane barriers. Membrane fusion is also a potentially efficient mechanism for the delivery of macromolecular therapeutics to the cellular cytoplasm. However, a key shortcoming of existing fusogenic liposomal systems is that they are inefficient, requiring a high concentration of fusion-promoting lipids in order to cross cellular membrane barriers. OBJECTIVES: Toward addressing this limitation, our experiments explore the extent to which membrane fusion can be amplified by using the process of lipid membrane phase separation to concentrate fusion-promoting lipids within distinct regions of the membrane surface. METHODS: We used confocal fluorescence microscopy to investigate the integration of fusion-promoting lipids into a ternary lipid membrane system that separated into liquid-ordered and liquid-disordered membrane phases. Additionally, we quantified the impact of membrane phase separation on the efficiency with which liposomes transferred lipids and encapsulated macromolecules to cells, using a combination of confocal fluorescence imaging and flow cytometry. RESULTS: Here we report that concentrating fusion-promoting lipids within phase-separated lipid domains on the surfaces of liposomes significantly increases the efficiency of liposome fusion with model membranes and cells. In particular, membrane phase separation enhanced the delivery of lipids and model macromolecules to the cytoplasm of tumor cells by at least four-fold in comparison to homogenous liposomes. CONCLUSIONS: Our findings demonstrate that phase separation can enhance membrane fusion by locally concentrating fusion-promoting lipids on the surface of liposomes. This work represents the first application of lipid membrane phase separation in the design of biomaterials-based delivery systems. Additionally, these results lay the ground work for developing fusogenic liposomes that are triggered by physical and molecular cues associated with target cells. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12195-017-0489-4) contains supplementary material, which is available to authorized users.",,"['Imam, Zachary I.', 'Kenyon, Laura E.', 'Ashby, Grant', 'Nagib, Fatema', 'Mendicino, Morgan', 'Zhao, Chi', 'Gadok, Avinash K.', 'Stachowiak, Jeanne C.']",,,,
,PMC,Persistent infections support maintenance of a coronavirus in a population of Australian bats (Myotis macropus),http://dx.doi.org/10.1017/S0950268817000991,PMC5776035,,,"Understanding viral transmission dynamics within populations of reservoir hosts can facilitate greater knowledge of the spillover of emerging infectious diseases. While bat-borne viruses are of concern to public health, investigations into their dynamics have been limited by a lack of longitudinal data from individual bats. Here, we examine capture–mark–recapture (CMR) data from a species of Australian bat (Myotis macropus) infected with a putative novel Alphacoronavirus within a Bayesian framework. Then, we developed epidemic models to estimate the effect of persistently infectious individuals (which shed viruses for extensive periods) on the probability of viral maintenance within the study population. We found that the CMR data analysis supported grouping of infectious bats into persistently and transiently infectious bats. Maintenance of coronavirus within the study population was more likely in an epidemic model that included both persistently and transiently infectious bats, compared with the epidemic model with non-grouping of bats. These findings, using rare CMR data from longitudinal samples of individual bats, increase our understanding of transmission dynamics of bat viral infectious diseases.",,"['JEONG, J.', 'SMITH, C. S.', 'PEEL, A. J.', 'PLOWRIGHT, R. K.', 'KERLIN, D. H.', 'MCBROOM, J.', 'MCCALLUM, H.']",,,,
,PMC,Serum amyloid A: an ozone-induced circulating factor with potentially important functions in the lung-brain axis,http://dx.doi.org/10.1096/fj.201600857RRR,PMC5572691,,,"Accumulating evidence suggests that O(3) exposure may contribute to CNS dysfunction. Here, we posit that inflammatory and acute-phase proteins in the circulation increase after O(3) exposure and systemically convey signals of O(3) exposure to the CNS. To model acute O(3) exposure, female Balb/c mice were exposed to 3 ppm O(3) or forced air for 2 h and were studied after 6 or 24 h. Of 23 cytokines and chemokines, only KC/CXCL1 was increased in blood 6 h after O(3) exposure. The acute-phase protein serum amyloid A (A-SAA) was significantly increased by 24 h, whereas C-reactive protein was unchanged. A-SAA in blood correlated with total leukocytes, macrophages, and neutrophils in bronchoalveolar lavage from O(3)-exposed mice. A-SAA mRNA and protein were increased in the liver. We found that both isoforms of A-SAA completely crossed the intact blood-brain barrier, although the rate of SAA2.1 influx was approximately 5 times faster than that of SAA1.1. Finally, A-SAA protein, but not mRNA, was increased in the CNS 24 h post-O(3) exposure. Our findings suggest that A-SAA is functionally linked to pulmonary inflammation in our O(3) exposure model and that A-SAA could be an important systemic signal of O(3) exposure to the CNS.—Erickson, M. A., Jude, J., Zhao, H., Rhea, E. M., Salameh, T. S., Jester, W., Pu, S., Harrowitz, J., Nguyen, N., Banks, W. A., Panettieri, R. A., Jr., Jordan-Sciutto, K. L. Serum amyloid A: an ozone-induced circulating factor with potentially important functions in the lung-brain axis.",,"['Erickson, Michelle A.', 'Jude, Joseph', 'Zhao, Hengjiang', 'Rhea, Elizabeth M.', 'Salameh, Therese S.', 'Jester, William', 'Pu, Shelley', 'Harrowitz, Jenna', 'Nguyen, Ngan', 'Banks, William A.', 'Panettieri, Reynold A.', 'Jordan-Sciutto, Kelly L.']",,,,
,PMC,Conservation Genetics of the Cheetah: Lessons Learned and New Opportunities,http://dx.doi.org/10.1093/jhered/esx047,PMC5892392,,,"The dwindling wildlife species of our planet have become a cause célèbre for conservation groups, governments, and concerned citizens throughout the world. The application of powerful new genetic technologies to surviving populations of threatened mammals has revolutionized our ability to recognize hidden perils that afflict them. We have learned new lessons of survival, adaptation, and evolution from viewing the natural history of genomes in hundreds of detailed studies. A single case history of one species, the African cheetah, Acinonyx jubatus, is here reviewed to reveal a long-term story of conservation challenges and action informed by genetic discoveries and insights. A synthesis of 3 decades of data, interpretation, and controversy, capped by whole genome sequence analysis of cheetahs, provides a compelling tale of conservation relevance and action to protect this species and other threatened wildlife.",,"['O’Brien, Stephen J', 'Johnson, Warren E', 'Driscoll, Carlos A', 'Dobrynin, Pavel', 'Marker, Laurie']",,,,
,PMC,The individual and population genetics of antibody immunity,http://dx.doi.org/10.1016/j.it.2017.04.003,PMC5656258,,,"Antibodies (Abs) produced by immunoglobulin (IG) genes are the most diverse proteins expressed in humans. While part of this diversity is generated by recombination during B cell development and mutations during affinity maturation, the germline IG loci are also diverse across human populations and ethnicities. Recently, proof-of-concept studies have demonstrated genotype-phenotype correlations between specific IG germline variants and the quality of Ab responses during vaccination and disease. However, the functional consequences of IG genetic variation in Ab function and immunological outcomes remain underexplored. Here we outline interconnections between IG genomic diversity and Ab expressed repertoires and structure. We further propose a strategy for integrating IG genotyping with functional Ab profiling data as a means to better predict and optimize humoral responses in genetically diverse human populations, with immediate implications for personalized medicine.",,"['Watson, Corey T.', 'Glanville, Jacob', 'Marasco, Wayne A.']",,,,
,PMC,Glutamine antagonist-mediated immune suppression decreases pathology but delays virus clearance in mice during nonfatal alphavirus encephalomyelitis,http://dx.doi.org/10.1016/j.virol.2017.05.013,PMC5510753,,,"Infection of weanling C57BL/6 mice with the TE strain of Sindbis virus (SINV) causes nonfatal encephalomyelitis associated with hippocampal-based memory impairment that is partially prevented by treatment with 6-diazo-5-oxo-l-norleucine (DON), a glutamine antagonist (Potter et al, J Neurovirol 21:159, 2015). To determine the mechanism(s) of protection, lymph node and central nervous system (CNS) tissues from SINV-infected mice treated daily for 1 week with low (0.3 mg/kg) or high (0.6 mg/kg) dose DON were examined. DON treatment suppressed lymphocyte proliferation in cervical lymph nodes resulting in reduced CNS immune cell infiltration, inflammation, and cell death compared to untreated SINV-infected mice. Production of SINV-specific antibody and interferon-gamma were also impaired by DON treatment with a delay in virus clearance. Cessation of treatment allowed activation of the antiviral immune response and viral clearance, but revived CNS pathology, demonstrating the ability of the immune response to mediate both CNS damage and virus clearance.",,"['Baxterb, Victoria K.', 'Glowinski, Rebecca', 'Braxton, Alicia M.', 'Potter, Michelle C.', 'Slusher, Barbara S.', 'Griffin, Diane E.']",,,,
,PMC,Vaccines for the common cold,http://dx.doi.org/10.1002/14651858.CD002190.pub5,PMC6481390,,,"BACKGROUND: The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore throat, and fever (usually < 37.8º C). The widespread morbidity caused by the common cold worldwide is related to its ubiquitousness rather than its severity. The development of vaccines for the common cold has been difficult because of antigenic variability of the common cold virus and the indistinguishable multiple other viruses and even bacteria acting as infective agents. There is uncertainty regarding the efficacy and safety of interventions for preventing the common cold in healthy people. This is an update of a Cochrane review first published in 2011 and previously updated in 2013. OBJECTIVES: To assess the clinical effectiveness and safety of vaccines for preventing the common cold in healthy people. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (September 2016), MEDLINE (1948 to September 2016), Embase (1974 to September 2016), CINAHL (1981 to September 2016), and LILACS (1982 to September 2016). We also searched three trials registers for ongoing studies and four websites for additional trials (February 2017). We included no language or date restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) of any virus vaccines compared with placebo to prevent the common cold in healthy people. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated methodological quality and extracted trial data. We resolved disagreements by discussion or by consulting a third review author. MAIN RESULTS: We found no additional RCTs for inclusion in this update. This review includes one RCT dating from the 1960s with an overall high risk of bias. The RCT included 2307 healthy participants, all of whom were included in analyses. This trial compared the effect of an adenovirus vaccine against placebo. No statistically significant difference in common cold incidence was found: there were 13 (1.14%) events in 1139 participants in the vaccines group and 14 (1.19%) events in 1168 participants in the placebo group (risk ratio 0.95, 95% confidence interval 0.45 to 2.02; P = 0.90). No adverse events related to the live vaccine were reported. The quality of the evidence was low due to limitations in methodological quality and a wide 95% confidence interval. AUTHORS' CONCLUSIONS: This Cochrane Review was based on one study with low‐quality evidence. We found no conclusive results to support the use of vaccines for preventing the common cold in healthy people compared with placebo. We identified a need for well‐designed, adequately powered RCTs to investigate vaccines for the common cold in healthy people. Any future trials on medical treatments for preventing the common cold should assess a variety of virus vaccines for this condition. Outcome measures should include common cold incidence, vaccine safety, and mortality related to the vaccine.",,"['Simancas‐Racines, Daniel', 'Franco, Juan VA', 'Guerra, Claudia V', 'Felix, Maria L', 'Hidalgo, Ricardo', 'Martinez‐Zapata, Maria José']",,,,
,PMC,Analysis of synonymous codon usage bias and phylogeny of coat protein gene in banana bract mosaic virus isolates,http://dx.doi.org/10.1007/s13337-017-0380-x,PMC5510630,,,"The banana is one of the world’s most important livelihood crops. Banana plants are principally infected by four virus species, Banana bunchy top virus (genus Babuvirus), Cucumber mosaic virus (genus Cucumovirus), Banana streak virus (genus Badnavirus) and Banana bract mosaic virus (genus Potyvirus). The objective of this study is to understand the codon usage pattern and phylogeny of coat protein gene in different banana bract mosaic virus (BBrMV) isolates. The BBrMV Coat Protein (CP) gene was amplified from BBrMV infected banana plant samples collected from different districts of Tamil Nadu and Karnataka, India. Six new BBrMV isolates were submitted to National Center for Biotechnology Information. Phylogenetic analysis and codon usage indices were studied along with other isolates of BBrMV. Phylogenetic analysis of CP genes shows that most of BBrMV isolates are closely related to each other except KF385484.1 and KF385478.1. Relative codon usage patterns among different BBrMV isolates were calculated by software CodonW version 1.4.2. In BBrMV, codons with A-ended or U ended are the most preferential except the Leu and Gln whose optimized codons are CAG and UUG ending by G. The codon usage patterns of BBrMV isolates are principally influenced by mutational bias; however, compositional constraints along with mutational bias also play a major role. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13337-017-0380-x) contains supplementary material, which is available to authorized users.",,"['Patil, Atul B.', 'Dalvi, Vijayendra S.', 'Mishra, Akhilesh A.', 'Krishna, Bal', 'Azeez, Abdul']",,,,
,PMC,"w09, a novel autophagy enhancer, induces autophagy-dependent cell apoptosis via activation of the EGFR-mediated RAS-RAF1-MAP2K-MAPK1/3 pathway",http://dx.doi.org/10.1080/15548627.2017.1319039,PMC5529067,,,"The EGFR (epidermal growth factor receptor) signaling pathway is frequently deregulated in many malignancies. Therefore, targeting the EGFR pathway is regarded as a promising strategy for anticancer drug discovery. Herein, we identified a 2-amino-nicotinonitrile compound (w09) as a novel autophagy enhancer, which potently induced macroautophagy/autophagy and consequent apoptosis in gastric cancer cells. Mechanistic studies revealed that EGFR-mediated activation of the RAS-RAF1-MAP2K-MAPK1/3 signaling pathway played a critical role in w09-induced autophagy and apoptosis of gastric cancer cells. Inhibition of the MAPK1/3 pathway with U0126 or blockade of autophagy by specific chemical inhibitors markedly attenuated the effect of w09-mediated growth inhibition and caspase-dependent apoptosis. Furthermore, these conclusions were supported by knockdown of ATG5 or knockout of ATG5 and/or ATG7. Notably, w09 increased the expression of SQSTM1 by transcription, and knockout of SQSTM1 or deleting the LC3-interaction region domain of SQSTM1, significantly inhibited w09-induced PARP1 cleavage, suggesting the central role played by SQSTM1 in w09-induced apoptosis. In addition, in vivo administration of w09 effectively inhibited tumor growth of SGC-7901 xenografts. Hence, our findings not only suggested that activation of the EGFR-RAS-RAF1-MAP2K-MAPK1/3 signaling pathway may play a critical role in w09-induced autophagy and apoptosis, but also imply that induction of autophagic cancer cell death through activation of the EGFR pathway may be a potential therapeutic strategy for EGFR-disregulated gastric tumors.",,"['Zhang, Pinghu', 'Zheng, Zuguo', 'Ling, Li', 'Yang, Xiaohui', 'Zhang, Ni', 'Wang, Xue', 'Hu, Maozhi', 'Xia, Yu', 'Ma, Yiwen', 'Yang, Haoran', 'Wang, Yunyi', 'Liu, Hongqi']",,,,
,PMC,The intergenic recombinant HLA-B*46:01 has a distinctive peptidome which includes KIR2DL3 ligands,http://dx.doi.org/10.1016/j.celrep.2017.04.059,PMC5510751,,,"HLA-B*46:01 was formed by an intergenic mini-conversion, between HLA-B*15:01 and HLA-C*01:02, in South-East Asia during the last 50,000 years and has since become the most common HLA-B allele in the region. A functional effect of the mini-conversion was introduction of the C1 epitope into HLA-B*46:01, making it an exceptional HLA-B allotype that is recognized by the C1-specific natural killer cell receptor KIR2DL3. High-resolution mass spectrometry showed that HLA-B*46:01 has a low diversity peptidome that is distinct from those of its parents. A minority (21%) of HLA-B*46:01 peptides, with common C-terminal characteristics, form ligands for KIR2DL3. The HLA-B*46:01 peptidome is predicted to be enriched for peptide antigens derived from Mycobacterium leprae. Overall, the results indicate that the distinctive peptidome and functions of HLA-B*46:01 provide carriers with resistance to leprosy, which drove its rapid rise in frequency in South-East Asia.",,"['Hilton, Hugo G.', 'McMurtrey, Curtis P.', 'Han, Alex S.', 'Djaoud, Zakia', 'Guethlein, Lisbeth A.', 'Blokhuis, Jeroen', 'Pugh, Jason L.', 'Goyos, Ana', 'Horowitz, Amir', 'Buchli, Rico', 'Jackson, Ken W.', 'Bardet, Wilfred', 'Bushnell, David A.', 'Robinson, Philip', 'Mendoza, Juan L.', 'Birnbaum, Michael E.', 'Nielsen, Morten', 'Garcia, K. Christopher', 'Hildebrand, William H.', 'Parham, Peter']",,,,
,PMC,Clinical Relevance and Role of Neuronal AT(1) Receptors in ADAM17-Mediated ACE2 Shedding in Neurogenic Hypertension,http://dx.doi.org/10.1161/CIRCRESAHA.116.310509,PMC5507353,,,"RATIONALE: Neurogenic hypertension is characterized by an increase in sympathetic activity and often resistance to drug treatments. We previously reported that it is also associated with a reduction of Angiotensin Converting Enzyme 2 (ACE2) and an increase in A Disintegrin And Metalloprotease 17 (ADAM17) activity in experimental hypertension. In addition, while multiple cells within the central nervous system have been involved in the development of neurogenic hypertension, the contribution of ADAM17 has not been investigated. OBJECTIVE: To assess the clinical relevance of this ADAM17-mediated ACE2 shedding in hypertensive patients and further identify the cell types and signaling pathways involved in this process. METHODS AND RESULTS: Using a mass spectrometry-based assay, we identified ACE2 as the main enzyme converting Ang II into Ang-(1–7) in human cerebrospinal fluid (CSF). We also observed an increase in ACE2 activity in the CSF of hypertensive patients, which was correlated with systolic blood pressure. Moreover, the increased level of tumor necrosis factor (TNF)-α in those CSF samples confirmed that ADAM17 was up-regulated in the hypertensive patients’ brain. To further assess the interaction between brain renin-angiotensin system and ADAM17, we generated mice lacking Angiotensin II type 1 receptors (AT(1)R) specifically on neurons. Our data reveal that despite expression on astrocytes and other cells types in the brain, ADAM17 up-regulation during DOCA-salt hypertension occurs selectively on neurons and neuronal AT(1)R are indispensable to this process. Mechanistically, reactive oxygen species (ROS) and extracellular signal-regulated kinase (ERK) were found to mediate ADAM17 activation. CONCLUSIONS: Our data demonstrate that AT(1)R promote ADAM17-mediated ACE2 shedding in the brain of hypertensive patients, leading to a loss in compensatory activity during neurogenic hypertension.",,"['Xu, Jiaxi', 'Sriramula, Srinivas', 'Xia, Huijing', 'Moreno-Walton, Lisa', 'Culicchia, Frank', 'Domenig, Oliver', 'Poglitsch, Marko', 'Lazartigues, Eric']",,,,
,PMC,A Consensus Definitive Classification of Scavenger Receptors and Their Roles in Health and Disease,http://dx.doi.org/10.4049/jimmunol.1700373,PMC5671342,,,"Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a diverse variety of ligands including endogenous and modified host-derived molecules and microbial pathogens. There are currently eight classes of scavenger receptors, many of which have multiple names, leading to inconsistencies and confusion in the literature. To address this problem, a workshop was organized by the United States National Institute of Allergy and Infectious Diseases, National Institutes of Health, to help develop a clear definition of scavenger receptors and a standardized nomenclature based on that definition. Fifteen experts in the scavenger receptor field attended the workshop and, after extensive discussion, reached a consensus regarding the definition of scavenger receptors and a proposed scavenger receptor nomenclature. Scavenger receptors were defined as cell surface receptors that typically bind multiple ligands and promote the removal of nonself or altered-self targets. They often function by mechanisms that include endocytosis, phagocytosis, adhesion, and signaling that ultimately lead to the elimination of degraded or harmful substances. Based on this definition, nomenclature and classification of these receptors into 10 classes were proposed. This classification was discussed at three national meetings and input from participants at these meetings was requested. The following manuscript is a consensus statement that combines the recommendations of the initial workshop and incorporates the input received from the participants at the three national meetings.",,"['PrabhuDas, Mercy R.', 'Baldwin, Cynthia L.', 'Bollyky, Paul L.', 'Bowdish, Dawn M. E.', 'Drickamer, Kurt', 'Febbraio, Maria', 'Herz, Joachim', 'Kobzik, Lester', 'Krieger, Monty', 'Loike, John', 'McVicker, Benita', 'Means, Terry K.', 'Moestrup, Soren K.', 'Post, Steven R.', 'Sawamura, Tatsuya', 'Silverstein, Samuel', 'Speth, Robert C.', 'Telfer, Janice C.', 'Thiele, Geoffrey M.', 'Wang, Xiang-Yang', 'Wright, Samuel D.', 'El Khoury, Joseph']",,,,
,PMC,Long-term safety from transmission of porcine endogenous retrovirus after pig-to-nonhuman primate corneal transplantation,http://dx.doi.org/10.1111/xen.12314,PMC5546926,,,"BACKGROUND: The risk of xenozoonosis mainly by porcine endogenous retrovirus (PERV) has been considered as one of the main hurdles in xenotransplantation and therefore should be elucidated prior to the clinical use of porcine corneal grafts. Accordingly, an investigation was performed to analyze the infectivity of PERVs from porcine keratocytes to human cells, and the long-term risk of transmission of PERVs was determined using pig-to-nonhuman primate (NHP) corneal transplantation models. METHODS: The infectivity of PERVs from the SNU miniature pig keratocytes was investigated by co-culture with a human embryonic kidney cell line. Twenty-two rhesus macaques underwent xenocorneal transplantation as follows: 1) group 1 (n=4): anterior lamellar keratoplasty (LKP) with freshly preserved porcine corneas, 2) group 2 (n=5): anterior LKP with decellularized porcine corneas followed by penetrating keratoplasty (PKP) with allografts, 3) group 3 (n=3): PKP under steroid-based immunosuppression, 4) group 4 (n=4): PKP under anti-CD154 antibody-based immunosuppression, 5) group 5 (n=4): deep anterior lamellar keratoplasty with freshly preserved porcine corneas under anti-CD40 antibody-based immunosuppression, and 6) group 6 (n=2): PKP under anti-CD40 antibody-based immunosuppression. Post-operative blood samples were serially collected, and tissue samples were obtained from thirteen different organs at the end of each experiment. The existence of PERV DNA and RNA was investigated using PCR and RT-PCR. RESULTS: Using two independent in vitro infectivity tests, neither PERV pol nor pig mitochondrial cytochrome oxidase II was detected after 41 and 92 days of co-culture, respectively. After xenocorneal transplantation, a total of 257 serial peripheral blood mononuclear cell samples, 34 serial plasma samples and 282 tissue samples were obtained from the NHP recipients up to 1176 days post-transplantation. No PERV transmission was evident in any samples. CONCLUSIONS: Within the limits of this study, there is no evidence to support any risk of PERV transmission from porcine corneal tissues to NHP recipients, despite the existence of PERV-expressing cells in porcine corneas.",,"['Choi, Hyuk Jin', 'Kim, Jiyeon', 'Kim, Jae Young', 'Lee, Hyun Ju', 'Wee, Won Ryang', 'Kim, Mee Kum', 'Hwang, Eung Soo']",,,,
,PMC,Viral hijacking of host caspases: an emerging category of pathogen–host interactions,http://dx.doi.org/10.1038/cdd.2017.59,PMC5520459,,,"Viruses co-evolve with their hosts, and many viruses have developed mechanisms to suppress or modify the host cell apoptotic response for their own benefit. Recently, evidence has emerged for the opposite strategy. Some viruses have developed the ability to co-opt apoptotic caspase activity to facilitate their own proliferation. In these strategies, viral proteins are cleaved by host caspases to create cleavage products with novel activities which facilitate viral replication. This represents a novel and interesting class of viral–host interactions, and also represents a new group of non-apoptotic roles for caspases. Here we review the evidence for such strategies, and discuss their origins and their implications for our understanding of the relationship between viral pathogenesis and programmed cell death.",,"['Connolly, Patrick F', 'Fearnhead, Howard O']",,,,
,PMC,Ebolaviruses Associated with Differential Pathogenicity Induce Distinct Host Responses in Human Macrophages,http://dx.doi.org/10.1128/JVI.00179-17,PMC5432886,,,"Ebola virus (EBOV) and Reston virus (RESTV) are members of the Ebolavirus genus which greatly differ in their pathogenicity. While EBOV causes a severe disease in humans characterized by a dysregulated inflammatory response and elevated cytokine and chemokine production, there are no reported disease-associated human cases of RESTV infection, suggesting that RESTV is nonpathogenic for humans. The underlying mechanisms determining the pathogenicity of different ebolavirus species are not yet known. In this study, we dissected the host response to EBOV and RESTV infection in primary human monocyte-derived macrophages (MDMs). As expected, EBOV infection led to a profound proinflammatory response, including strong induction of type I and type III interferons (IFNs). In contrast, RESTV-infected macrophages remained surprisingly silent. Early activation of IFN regulatory factor 3 (IRF3) and NF-κB was observed in EBOV-infected, but not in RESTV-infected, MDMs. In concordance with previous results, MDMs treated with inactivated EBOV and Ebola virus-like particles (VLPs) induced NF-κB activation mediated by Toll-like receptor 4 (TLR4) in a glycoprotein (GP)-dependent manner. This was not the case in cells exposed to live RESTV, inactivated RESTV, or VLPs containing RESTV GP, indicating that RESTV GP does not trigger TLR4 signaling. Our results suggest that the lack of immune activation in RESTV-infected MDMs contributes to lower pathogenicity by preventing the cytokine storm observed in EBOV infection. We further demonstrate that inhibition of TLR4 signaling abolishes EBOV GP-mediated NF-κB activation. This finding indicates that limiting the excessive TLR4-mediated proinflammatory response in EBOV infection should be considered as a potential supportive treatment option for EBOV disease. IMPORTANCE Emerging infectious diseases are a major public health concern, as exemplified by the recent devastating Ebola virus (EBOV) outbreak. Different ebolavirus species are associated with widely varying pathogenicity in humans, ranging from asymptomatic infections for Reston virus (RESTV) to severe disease with fatal outcomes for EBOV. In this comparative study of EBOV- and RESTV-infected human macrophages, we identified key differences in host cell responses. Consistent with previous data, EBOV infection is associated with a proinflammatory signature triggered by the surface glycoprotein (GP), which can be inhibited by blocking TLR4 signaling. In contrast, infection with RESTV failed to stimulate a strong host response in infected macrophages due to the inability of RESTV GP to stimulate TLR4. We propose that disparate proinflammatory host signatures contribute to the differences in pathogenicity reported for ebolavirus species and suggest that proinflammatory pathways represent an intriguing target for the development of novel therapeutics.",,"['Olejnik, Judith', 'Forero, Adriana', 'Deflubé, Laure R.', 'Hume, Adam J.', 'Manhart, Whitney A.', 'Nishida, Andrew', 'Marzi, Andrea', 'Katze, Michael G.', 'Ebihara, Hideki', 'Rasmussen, Angela L.', 'Mühlberger, Elke']",,,,
,PMC,Multiple Sources of Genetic Diversity of Influenza A Viruses during the Hajj,http://dx.doi.org/10.1128/JVI.00096-17,PMC5432881,,,"Outbreaks of respiratory virus infection at mass gatherings pose significant health risks to attendees, host communities, and ultimately the global population if they help facilitate viral emergence. However, little is known about the genetic diversity, evolution, and patterns of viral transmission during mass gatherings, particularly how much diversity is generated by in situ transmission compared to that imported from other locations. Here, we describe the genome-scale evolution of influenza A viruses sampled from the Hajj pilgrimages at Makkah during 2013 to 2015. Phylogenetic analysis revealed that the diversity of influenza viruses at the Hajj pilgrimages was shaped by multiple introduction events, comprising multiple cocirculating lineages in each year, including those that have circulated in the Middle East and those whose origins likely lie on different continents. At the scale of individual hosts, the majority of minor variants resulted from de novo mutation, with only limited evidence of minor variant transmission or minor variants circulating at subconsensus level despite the likely identification of multiple transmission clusters. Together, these data highlight the complexity of influenza virus infection at the Hajj pilgrimages, reflecting a mix of global genetic diversity drawn from multiple sources combined with local transmission, and reemphasize the need for vigilant surveillance at mass gatherings. IMPORTANCE Large population sizes and densities at mass gatherings such as the Hajj (Makkah, Saudi Arabia) can contribute to outbreaks of respiratory virus infection by providing local hot spots for transmission followed by spread to other localities. Using a genome-scale analysis, we show that the genetic diversity of influenza A viruses at the Hajj gatherings during 2013 to 2015 was largely shaped by the introduction of multiple viruses from diverse geographic regions, including the Middle East, with only little evidence of interhost virus transmission at the Hajj and seemingly limited spread of subconsensus mutational variants. The diversity of viruses at the Hajj pilgrimages highlights the potential for lineage cocirculation during mass gatherings, in turn fuelling segment reassortment and the emergence of novel variants, such that the continued surveillance of respiratory pathogens at mass gatherings should be a public health priority.",,"['Cobbin, Joanna C. A.', 'Alfelali, Mohammad', 'Barasheed, Osamah', 'Taylor, Janette', 'Dwyer, Dominic E.', 'Kok, Jen', 'Booy, Robert', 'Holmes, Edward C.', 'Rashid, Harunor']",,,,
,PMC,Structural Insights into Human Bocaparvoviruses,http://dx.doi.org/10.1128/JVI.00261-17,PMC5432872,,,"Bocaparvoviruses are emerging pathogens of the Parvoviridae family. Human bocavirus 1 (HBoV1) causes severe respiratory infections and HBoV2 to HBoV4 cause gastrointestinal infections in young children. Recent reports of life-threatening cases, lack of direct treatment or vaccination, and a limited understanding of their disease mechanisms highlight the need to study these pathogens on a molecular and structural level for the development of therapeutics. Toward this end, the capsid structures of HBoV1, HBoV3, and HBoV4 were determined to a resolution of 2.8 to 3.0 Å by cryo-electron microscopy and three-dimensional image reconstruction. The bocaparvovirus capsids, which display different tissue tropisms, have features in common with other parvoviruses, such as depressions at the icosahedral 2-fold symmetry axis and surrounding the 5-fold symmetry axis, protrusions surrounding the 3-fold symmetry axis, and a channel at the 5-fold symmetry axis. However, unlike other parvoviruses, densities extending the 5-fold channel into the capsid interior are conserved among the bocaparvoviruses and are suggestive of a genus-specific function. Additionally, their major viral protein 3 contains loops with variable regions at their apexes conferring capsid surface topologies different from those of other parvoviruses. Structural comparisons at the strain (HBoV) and genus (bovine parvovirus and HBoV) levels identified differences in surface loops that are functionally important in host/tissue tropism, pathogenicity, and antigenicity in other parvoviruses and likely play similar roles in these viruses. This study thus provides a structural framework to characterize determinants of host/tissue tropism, pathogenicity, and antigenicity for the development of antiviral strategies to control human bocavirus infections. IMPORTANCE Human bocaviruses are one of only a few members of the Parvoviridae family pathogenic to humans, especially young children and immunocompromised adults. There are currently no treatments or vaccines for these viruses or the related enteric bocaviruses. This study obtained the first high-resolution structures of three human bocaparvoviruses determined by cryo-reconstruction. HBoV1 infects the respiratory tract, and HBoV3 and HBoV4 infect the gastrointestinal tract, tissues that are likely targeted by the capsid. Comparison of these viruses provides information on conserved bocaparvovirus-specific features and variable regions resulting in unique surface topologies that can serve as guides to characterize HBoV determinants of tissue tropism and antigenicity in future experiments. Based on the comparison to other existing parvovirus capsid structures, this study suggests capsid regions that likely control successful infection, including determinants of receptor attachment, host cell trafficking, and antigenic reactivity. Overall, these observations could impact efforts to design antiviral strategies and vaccines for HBoVs.",,"['Mietzsch, Mario', 'Kailasan, Shweta', 'Garrison, Jamie', 'Ilyas, Maria', 'Chipman, Paul', 'Kantola, Kalle', 'Janssen, Mandy E.', 'Spear, John', 'Sousa, Duncan', 'McKenna, Robert', 'Brown, Kevin', 'Söderlund-Venermo, Maria', 'Baker, Timothy', 'Agbandje-McKenna, Mavis']",,,,
,PMC,pH Optimum of Hemagglutinin-Mediated Membrane Fusion Determines Sensitivity of Influenza A Viruses to the Interferon-Induced Antiviral State and IFITMs,http://dx.doi.org/10.1128/JVI.00246-17,PMC5432869,,,"The replication and pathogenicity of influenza A viruses (IAVs) critically depend on their ability to tolerate the antiviral interferon (IFN) response. To determine a potential role for the IAV hemagglutinin (HA) in viral sensitivity to IFN, we studied the restriction of IAV infection in IFN-β-treated human epithelial cells by using 2:6 recombinant IAVs that shared six gene segments of A/Puerto Rico/8/1934 virus (PR8) and contained HAs and neuraminidases of representative avian, human, and zoonotic H5N1 and H7N9 viruses. In A549 and Calu-3 cells, viruses displaying a higher pH optimum of HA-mediated membrane fusion, H5N1-PR8 and H7N9-PR8, were less sensitive to the IFN-induced antiviral state than their counterparts with HAs from duck and human viruses, which fused at a lower pH. The association between a high pH optimum of fusion and reduced IFN sensitivity was confirmed by using HA point mutants of A/Hong Kong/1/1968-PR8 that differed solely by their fusion properties. Furthermore, similar effects of the viral fusion pH on IFN sensitivity were observed in experiments with (i) primary human type II alveolar epithelial cells and differentiated cultures of human airway epithelial cells, (ii) nonrecombinant zoonotic and pandemic IAVs, and (iii) preparations of IFN-α and IFN-λ1. A higher pH of membrane fusion and reduced sensitivity to IFN correlated with lower restriction of the viruses in MDCK cells stably expressing the IFN-inducible transmembrane proteins IFITM2 and IFITM3, which are known to inhibit viral fusion. Our results reveal that the pH optimum of HA-driven membrane fusion of IAVs is a determinant of their sensitivity to IFN and IFITM proteins. IMPORTANCE The IFN system constitutes an important innate defense against viral infection. Substantial information is available on how IAVs avoid detection by sensors of the IFN system and disable IFN signaling pathways. Much less is known about the ability of IAVs to tolerate the antiviral activity of IFN-induced cellular proteins. The IFN-induced proteins of the IFITM family block IAV entry into target cells and can restrict viral spread and pathogenicity. Here we show for the first time that the sensitivity of IAVs to the IFN-induced antiviral state and IFITM2 and IFITM3 proteins depends on the pH value at which the viral HA undergoes a conformational transition and mediates membrane fusion. Our data imply that the high pH optimum of membrane fusion typical of zoonotic IAVs of gallinaceous poultry, such as H5N1 and H7N9, may contribute to their enhanced virulence in humans.",,"['Gerlach, Thomas', 'Hensen, Luca', 'Matrosovich, Tatyana', 'Bergmann, Janina', 'Winkler, Michael', 'Peteranderl, Christin', 'Klenk, Hans-Dieter', 'Weber, Friedemann', 'Herold, Susanne', 'Pöhlmann, Stefan', 'Matrosovich, Mikhail']",,,,
,PMC,Structural Characterization of Human Coronavirus NL63 N Protein,http://dx.doi.org/10.1128/JVI.02503-16,PMC5432860,,,"Coronaviruses are responsible for upper and lower respiratory tract infections in humans. It is estimated that 1 to 10% of the population suffers annually from cold-like symptoms related to infection with human coronavirus NL63 (HCoV-NL63), an alphacoronavirus. The nucleocapsid (N) protein, the major structural component of the capsid, facilitates RNA packing, links the capsid to the envelope, and is also involved in multiple other processes, including viral replication and evasion of the immune system. Although the role of N protein in viral replication is relatively well described, no structural data are currently available regarding the N proteins of alphacoronaviruses. Moreover, our understanding of the mechanisms of RNA binding and nucleocapsid formation remains incomplete. In this study, we solved the crystal structures of the N- and C-terminal domains (NTD, residues 10 to 140, and CTD, residues 221 to 340, respectively) of the N protein of HCoV-NL63, both at a 1.5-Å resolution. Based on our structure of NTD solved here, we proposed and experimentally evaluated a model of RNA binding. The structure of the CTD reveals the mode of N protein dimerization. Overall, this study expands our understanding of the initial steps of N protein-nucleic acid interaction and may facilitate future efforts to control the associated infections. IMPORTANCE Coronaviruses are responsible for the common cold and other respiratory tract infections in humans. According to multiple studies, 1 to 10% of the population is infected each year with HCoV-NL63. Viruses are relatively simple organisms composed of a few proteins and the nucleic acids that carry the information determining their composition. The nucleocapsid (N) protein studied in this work protects the nucleic acid from the environmental factors during virus transmission. This study investigated the structural arrangement of N protein, explaining the first steps of its interaction with nucleic acid at the initial stages of virus structure assembly. The results expand our understanding of coronavirus physiology and may facilitate future efforts to control the associated infections.",,"['Szelazek, Bozena', 'Kabala, Wojciech', 'Kus, Krzysztof', 'Zdzalik, Michal', 'Twarda-Clapa, Aleksandra', 'Golik, Przemyslaw', 'Burmistrz, Michal', 'Florek, Dominik', 'Wladyka, Benedykt', 'Pyrc, Krzysztof', 'Dubin, Grzegorz']",,,,
,PMC,Authors’ correction for Euro Surveill. 2017;22(11),http://dx.doi.org/10.2807/1560-7917.ES.2017.22.19.30531,PMC5476985,28537549,CC BY,,2017 May 11,,Euro Surveill,,,
,PMC,Chalcone: A Privileged Structure in Medicinal Chemistry,http://dx.doi.org/10.1021/acs.chemrev.7b00020,PMC6131713,,,"Privileged structures have been widely used as an effective template in medicinal chemistry for drug discovery. Chalcone is a common simple scaffold found in many naturally occurring compounds. Many chalcone derivatives have also been prepared due to their convenient synthesis. These natural products and synthetic compounds have shown numerous interesting biological activities with clinical potentials against various diseases. This review aims to highlight the recent evidence of chalcone as a privileged scaffold in medicinal chemistry. Multiple aspects of chalcone will be summarized herein, including the isolation of novel chalcone derivatives, the development of new synthetic methodologies, the evaluation of their biological properties, and the exploration of the mechanisms of action as well as target identification. This review is expected to be a comprehensive, authoritative, and critical review of the chalcone template to the chemistry community.",,"['Zhuang, Chunlin', 'Zhang, Wen', 'Sheng, Chunquan', 'Zhang, Wannian', 'Xing, Chengguo', 'Miao, Zhenyuan']",,,,
,PMC,Molecular characterization and phylogenetic analyses of virulent infectious bronchitis viruses isolated from chickens in Eastern Saudi Arabia,http://dx.doi.org/10.1007/s13337-017-0375-7,PMC5510638,,,"Infectious bronchitis virus (IBV) is one of the major respiratory viral threats for chickens. Despite the intensive application of IBV vaccines, several outbreaks have been reported worldwide. Here, we report several IBV outbreaks in thirteen poultry farms in Eastern Saudi Arabia (ESA) from 2013 to 2014. The main goals of the current study were as follows: (1) isolation and molecular characterization of the currently circulating strains in ESA (Al-Hasa, Dammam, and Buqayq) and (2) evaluation of the immune status of these birds to IBV. To achieve our goals, tissue specimens (trachea, lungs, liver, kidney and cecal tonsils) and sera were collected. High morbidity up to 100% and mortality ranging from 18 to 90% were reported. Severe infection was observed in the trachea, bronchi, and kidneys of the infected birds. IBV strains were isolated using embryonated chicken eggs. The isolated viruses induced hemorrhage, dwarfing and death of the inoculated embryos 3–5 days post-infection. The circulating IBV strains were identified by sequencing the partial IBV-N and IBV-S1 genes. These viruses showed 95% sequence identity to Indian, Italian, Egyptian and Chinese strains and were quite distinct from the locally used vaccines on the genomic level. Interestingly, high antibody titers against IBV were reported in some of these farms, suggesting the presence of new virulent strains in ESA. The seroconversion of infected birds was reported among the affected flocks. In conclusion, very virulent IBV strains are currently circulating in ESA. Further studies are currently in progress to molecularly characterize these IBV strains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13337-017-0375-7) contains supplementary material, which is available to authorized users.",,"['Hemida, Maged Gomaa', 'Al-Hammadi, Mohammed A.', 'Daleb, Abdul Hafeed S.', 'Gonsalves, Cecilio R.']",,,,
,PMC,Crimean-Congo Hemorrhagic Fever in Humanized Mice Reveals Glial Cells as Primary Targets of Neurological Infection,http://dx.doi.org/10.1093/infdis/jix215,PMC5853341,,,"Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral hemorrhagic disease seen exclusively in humans. Central nervous system (CNS) infection and neurological involvement have also been reported in CCHF. In the current study, we inoculated NSG-SGM3 mice engrafted with human hematopoietic CD34(+) stem cells with low-passage CCHF virus strains isolated from human patients. In humanized mice, lethal disease develops, characterized by histopathological change in the liver and brain. To date, targets of neurological infection and disease have not been investigated in CCHF. CNS disease in humanized mice was characterized by gliosis, meningitis, and meningoencephalitis, and glial cells were identified as principal targets of infection. Humanized mice represent a novel lethal model for studies of CCHF countermeasures, and CCHF-associated CNS disease. Our data suggest a role for astrocyte dysfunction in neurological disease and identify key regions of infection in the CNS for future investigations of CCHF.",,"['Spengler, Jessica R', 'Kelly Keating, M', 'McElroy, Anita K', 'Zivcec, Marko', 'Coleman-McCray, JoAnn D', 'Harmon, Jessica R', 'Bollweg, Brigid C', 'Goldsmith, Cynthia S', 'Bergeron, Éric', 'Keck, James G', 'Zaki, Sherif R', 'Nichol, Stuart T', 'Spiropoulou, Christina F']",,,,
,PMC,An optimized method for enumerating CNS derived memory B cells during viral-induced inflammation,http://dx.doi.org/10.1016/j.jneumeth.2017.05.011,PMC5545894,,,"BACKGROUND: CNS inflammation resulting from infection, injury, or neurodegeneration leads to accumulation of diverse B cell subsets. Although antibody secreting cells (ASC) within the inflamed CNS have been extensively examined, memory B cell (Bmem) characterization has been limited as they do not secrete antibody without stimulation. Moreover, unlike human Bmem, reliable surface markers for murine Bmem remain elusive. NEW METHOD: Using a viral encephalomyelitis model we developed a modified limiting dilution in vitro stimulation assay to convert CNS-derived virus specific Bmem into ASC. COMPARISON WITH EXISTING METHODS: Stimulation methods established for lymphoid tissue cells using prolonged stimulation with viral lysate resulted in substantial ASC loss and minimal Bmem to ASC conversion of CNS-derived cells. By varying stimulation duration, TLR activators, and culture supplements, we achieved optimal conversion by culturing cells with TLR7/8 agonist R848 in the presence of feeder cells for 2 days. RESULTS: Flow cytometry markers CD38 and CD73 characterizing murine Bmem from lymphoid tissue showed more diverse expression patterns on corresponding CNS-derived B cell subsets. Using the optimized TLR7/8 stimulation protocol, we compared virus-specific IgG Bmem versus pre-existing ASC within the brain and spinal cord. Increasing Bmem frequencies during chronic infection mirrored kinetics of ASC. However, despite initially similar Bmem and ASC accumulation, Bmem prevailed in the brain, but were lower than ASC in the spinal cord during persistence. CONCLUSION: Simultaneous enumeration of antigen-specific Bmem and ASC using the Bmem assay optimized for CNS-derived cells enables characterization of temporal changes during microbial or auto-antigen induced neuroinflammation.",,"['DiSano, Krista D.', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.']",,,,
,PMC,Epidemiology and Clinical Features of Human Coronaviruses in the Pediatric Population,http://dx.doi.org/10.1093/jpids/pix027,PMC5954244,,,"BACKGROUND: The epidemiology and clinical features of human coronaviruses (HCoVs) in children are not fully characterized. METHODS: A retrospective study of children with HCoV detected by reverse-transcriptase polymerase chain reaction (RT-PCR) was performed for a community cohort and a children’s hospital in the same community from January 2013 to December 2014. The RT-PCR assay detected HCoV 229E, HKU1, NL63, and OC43 in nasal swabs from symptomatic children ≤18 years. Factors associated with increased severity of illness in hospitalized children were assessed by multivariable logistic regression. RESULTS: Human coronavirus was detected in 261 children, 49 and 212 from the community and hospital, respectively. The distribution of HCoV types and seasonal trends were similar in the community and hospital. Community cases were older than hospitalized cases (median age, 4.4 versus 1.7 years, respectively; P < .01), and a minority of community cases (26.5%) sought medical attention. Among the hospitalized children with HCoV detected, 39 (18.4%) received respiratory support and 24 (11.3%) were admitted to the pediatric intensive care unit (PICU). Age <2 years (odds ratio [OR] = 5.0; 95% confidence interval [CI], 1.9–13.1) and cardiovascular (OR = 3.9; 95% CI, 1.6–9.5), genetic/congenital (OR = 2.8; 95% CI, 1.1–7.0), and respiratory chronic complex conditions ([CCCs] OR = 4.5; 95% CI, 1.7–12.0) were associated with receiving respiratory support. Genetic/congenital (OR = 2.8; 95% CI, 1.1–7.4) CCCs were associated with PICU admission. Severity of illness was similar among hospitalized children with different HCoV types. CONCLUSIONS: Children in the community with HCoV detected generally had mild illness as demonstrated by few medically attended cases. In hospitalized children, young age and CCCs, but not HCoV type, were associated with increased severity of illness.",,"['Varghese, Litty', 'Zachariah, Philip', 'Vargas, Celibell', 'LaRussa, Philip', 'Demmer, Ryan T', 'Furuya, Yoko E', 'Whittier, Susan', 'Reed, Carrie', 'Stockwell, Melissa S', 'Saiman, Lisa']",,,,
,PMC,Coronavirus nonstructural protein 15 mediates evasion of dsRNA sensors and limits apoptosis in macrophages,http://dx.doi.org/10.1073/pnas.1618310114,PMC5448190,,,"Coronaviruses are positive-sense RNA viruses that generate double-stranded RNA (dsRNA) intermediates during replication, yet evade detection by host innate immune sensors. Here we report that coronavirus nonstructural protein 15 (nsp15), an endoribonuclease, is required for evasion of dsRNA sensors. We evaluated two independent nsp15 mutant mouse coronaviruses, designated N15m1 and N15m3, and found that these viruses replicated poorly and induced rapid cell death in mouse bone marrow-derived macrophages. Infection of macrophages with N15m1, which expresses an unstable nsp15, or N15m3, which expresses a catalysis-deficient nsp15, activated MDA5, PKR, and the OAS/RNase L system, resulting in an early, robust induction of type I IFN, PKR-mediated apoptosis, and RNA degradation. Immunofluorescence imaging of nsp15 mutant virus-infected macrophages revealed significant dispersal of dsRNA early during infection, whereas in WT virus-infected cells, the majority of the dsRNA was associated with replication complexes. The loss of nsp15 activity also resulted in greatly attenuated disease in mice and stimulated a protective immune response. Taken together, our findings demonstrate that coronavirus nsp15 is critical for evasion of host dsRNA sensors in macrophages and reveal that modulating nsp15 stability and activity is a strategy for generating live-attenuated vaccines.",,"['Deng, Xufang', 'Hackbart, Matthew', 'Mettelman, Robert C.', 'O’Brien, Amornrat', 'Mielech, Anna M.', 'Yi, Guanghui', 'Kao, C. Cheng', 'Baker, Susan C.']",,,,
,PMC,"Preliminary Epidemiologic Assessment of Human Infections With Highly Pathogenic Avian Influenza A(H5N6) Virus, China",http://dx.doi.org/10.1093/cid/cix334,PMC5848334,,,"BACKGROUND. Since 2014, 17 human cases of infection with the newly emerged highly pathogenic avian influenza A(H5N6) virus have been identified in China to date. The epidemiologic characteristics of laboratory-confirmed A(H5N6) cases were compared to A(H5N1) and A(H7N9) cases in mainland China. METHODS. Data on laboratory-confirmed H5N6, H5N1, and H7N9 cases identified in mainland China were analyzed to compare epidemiologic characteristics and clinical severity. Severity of confirmed H5N6, H5N1 and H7N9 cases was estimated based on the risk of severe outcomes in hospitalized cases. RESULTS. H5N6 cases were older than H5N1 cases with a higher prevalence of underlying medical conditions but younger than H7N9 cases. Epidemiological time-to-event distributions were similar among cases infected with the 3 viruses. In comparison to a fatality risk of 70% (30/43) for hospitalized H5N1 cases and 41% (319/782) for hospitalized H7N9 cases, 12 (75%) out of the 16 hospitalized H5N6 cases were fatal, and 15 (94%) required mechanical ventilation. CONCLUSION. Similar epidemiologic characteristics and high severity were observed in cases of H5N6 and H5N1 virus infection, whereas severity of H7N9 virus infections appeared lower. Continued surveillance of human infections with avian influenza A viruses remains an essential component of pandemic influenza preparedness.",,"['Jiang, Hui', 'Wu, Peng', 'Uyeki, Timothy M.', 'He, Jianfeng', 'Deng, Zhihong', 'Xu, Wen', 'Lv, Qiang', 'Zhang, Jin', 'Wu, Yang', 'Tsang, Tim K.', 'Kang, Min', 'Zheng, Jiandong', 'Wang, Lili', 'Yang, Bingyi', 'Qin, Ying', 'Feng, Luzhao', 'Fang, Vicky J.', 'Gao, George F.', 'Leung, Gabriel M.', 'Yu, Hongjie', 'Cowling, Benjamin J.']",,,,
,PMC,Compartmental Model Diagrams as Causal Representations in Relation to DAGs,http://dx.doi.org/10.1515/em-2016-0007,PMC6294476,,,"Compartmental model diagrams have been used for nearly a century to depict causal relationships in infectious disease epidemiology. Causal directed acyclic graphs (DAGs) have been used more broadly in epidemiology since the 1990s to guide analyses of a variety of public health problems. Using an example from chronic disease epidemiology, the effect of type 2 diabetes on dementia incidence, we illustrate how compartmental model diagrams can represent the same concepts as causal DAGs, including causation, mediation, confounding, and collider bias. We show how to use compartmental model diagrams to explicitly depict interaction and feedback cycles. While DAGs imply a set of conditional independencies, they do not define conditional distributions parametrically. Compartmental model diagrams parametrically (or semiparametrically) describe state changes based on known biological processes or mechanisms. Compartmental model diagrams are part of a long-term tradition of causal thinking in epidemiology and can parametrically express the same concepts as DAGs, as well as explicitly depict feedback cycles and interactions. As causal inference efforts in epidemiology increasingly draw on simulations and quantitative sensitivity analyses, compartmental model diagrams may be of use to a wider audience. Recognizing simple links between these two common approaches to representing causal processes may facilitate communication between researchers from different traditions.",,"['Ackley, S. F.', 'Mayeda, E. R.', 'Worden, L.', 'Enanoria, W. T. A.', 'Glymour, M. M.', 'Porco, T. C.']",,,,
,PMC,"Broad-spectrum agents for flaviviral infections: Dengue, Zika and beyond",http://dx.doi.org/10.1038/nrd.2017.33,PMC5925760,,,"Infections with flaviviruses, such as dengue, West Nile virus, and the recently re-emerging Zika virus are an increasing and probably lasting global risk. This review summarizes and comments on the opportunities for broad-spectrum agents that are active against a range of flaviviruses. Broad-spectrum activity would be particularly desirable as preparatory measure for the next flaviviral epidemic that could emerge from as-yet-unknown or neglected viruses. Potential target sites for broad-spectrum anti-flaviviral compounds include viral proteins and host mechanisms that are exploited by these viruses during entry and replication. A variety of compounds with broad-spectrum antiviral activity have already been identified by target-specific or phenotypic assays. For some other compound classes, broad-spectrum activity can be anticipated because of their mode of action and molecular target(s).",,"['Boldescu, Veaceslav', 'Behnam, Mira A. M.', 'Vasilakis, Nikos', 'Klein, Christian D.']",,,,
,PMC,Zika virus induces massive cytoplasmic vacuolization and paraptosis‐like death in infected cells,http://dx.doi.org/10.15252/embj.201695597,PMC5470047,,,"The cytopathic effects of Zika virus (ZIKV) are poorly characterized. Innate immunity controls ZIKV infection and disease in most infected patients through mechanisms that remain to be understood. Here, we studied the morphological cellular changes induced by ZIKV and addressed the role of interferon‐induced transmembrane proteins (IFITM), a family of broad‐spectrum antiviral factors, during viral replication. We report that ZIKV induces massive vacuolization followed by “implosive” cell death in human epithelial cells, primary skin fibroblasts and astrocytes, a phenomenon which is exacerbated when IFITM3 levels are low. It is reminiscent of paraptosis, a caspase‐independent, non‐apoptotic form of cell death associated with the formation of large cytoplasmic vacuoles. We further show that ZIKV‐induced vacuoles are derived from the endoplasmic reticulum (ER) and dependent on the PI3K/Akt signaling axis. Inhibiting the Sec61 ER translocon in ZIKV‐infected cells blocked vacuole formation and viral production. Our results provide mechanistic insight behind the ZIKV‐induced cytopathic effect and indicate that IFITM3, by acting as a gatekeeper for incoming virus, restricts virus takeover of the ER and subsequent cell death.",,"['Monel, Blandine', 'Compton, Alex A', 'Bruel, Timothée', 'Amraoui, Sonia', 'Burlaud‐Gaillard, Julien', 'Roy, Nicolas', 'Guivel‐Benhassine, Florence', 'Porrot, Françoise', 'Génin, Pierre', 'Meertens, Laurent', 'Sinigaglia, Laura', 'Jouvenet, Nolwenn', 'Weil, Robert', 'Casartelli, Nicoletta', 'Demangel, Caroline', 'Simon‐Lorière, Etienne', 'Moris, Arnaud', 'Roingeard, Philippe', 'Amara, Ali', 'Schwartz, Olivier']",,,,
,PMC,"Motorcycles, Cell Phones, and Electricity Can Dramatically Change the Epidemiology of Infectious Disease in Africa",http://dx.doi.org/10.4269/ajtmh.16-0290,PMC5417187,,,"Some observations and recent publications demonstrated, particularly in Africa, the potential influence that low-cost motorcycles, cell phones, and even widespread electrification could have on the evolution of infectious diseases, particularly zoonoses. Our reflections support the conclusion that we should focus on the real-time surveillance systems including alerting systems leading to a rapid and flexible response rather than the strongly limited modeling of infectious diseases because of the continuous evolution of microorganisms, as well as changes in the environment and human habits that are unpredictable.",,"['Lagier, Jean-Christophe', 'Sokhna, Cheikh', 'Raoult, Didier']",,,,
,PMC,Constructing Ebola transmission chains from West Africa and estimating model parameters using internet sources,http://dx.doi.org/10.1017/S0950268817000760,PMC5830111,,,"During the recent Ebola crisis in West Africa, individual person-level details of disease onset, transmissions, and outcomes such as survival or death were reported in online news media. We set out to document disease transmission chains for Ebola, with the goal of generating a timely account that could be used for surveillance, mathematical modeling, and public health decision-making. By accessing public web pages only, such as locally produced newspapers and blogs, we created a transmission chain involving two Ebola clusters in West Africa that compared favorably with other published transmission chains, and derived parameters for a mathematical model of Ebola disease transmission that were not statistically different from those derived from published sources. We present a protocol for responsibly gleaning epidemiological facts, transmission model parameters, and useful details from affected communities using mostly indigenously produced sources. After comparing our transmission parameters to published parameters, we discuss additional benefits of our method, such as gaining practical information about the affected community, its infrastructure, politics, and culture. We also briefly compare our method to similar efforts that used mostly non-indigenous online sources to generate epidemiological information.",,"['PETTEY, W. B. P.', 'CARTER, M. E.', 'A TOTH, D. J.', 'SAMORE, M. H.', 'GUNDLAPALLI, A. V.']",,,,
,PMC,Burden and Seasonality of Viral Acute Respiratory Tract Infections among Outpatients in Southern Sri Lanka,http://dx.doi.org/10.4269/ajtmh.17-0032,PMC5508919,,,"In tropical and subtropical settings, the epidemiology of viral acute respiratory tract infections varies widely between countries. We determined the etiology, seasonality, and clinical presentation of viral acute respiratory tract infections among outpatients in southern Sri Lanka. From March 2013 to January 2015, we enrolled outpatients presenting with influenza-like illness (ILI). Nasal/nasopharyngeal samples were tested in duplicate using antigen-based rapid influenza testing and multiplex polymerase chain reaction (PCR) for respiratory viruses. Monthly proportion positive was calculated for each virus. Bivariable and multivariable logistic regression were used to identify associations between sociodemographic/clinical information and viral detection. Of 571 subjects, most (470, 82.3%) were ≥ 5 years of age and 53.1% were male. A respiratory virus was detected by PCR in 63.6% (N = 363). Common viral etiologies included influenza (223, 39%), human enterovirus/rhinovirus (HEV/HRV, 14.5%), respiratory syncytial virus (RSV, 4.2%), and human metapneumovirus (hMPV, 3.9%). Both ILI and influenza showed clear seasonal variation, with peaks from March to June each year. RSV and hMPV activity peaked from May to July, whereas HEV/HRV was seen year-round. Patients with respiratory viruses detected were more likely to report pain with breathing (odds ratio [OR] = 2.60, P = 0.003), anorexia (OR = 2.29, P < 0.001), and fatigue (OR = 2.00, P = 0.002) compared with patients with no respiratory viruses detected. ILI showed clear seasonal variation in southern Sri Lanka, with most activity during March to June; peak activity was largely due to influenza. Targeted infection prevention activities such as influenza vaccination in January–February may have a large public health impact in this region.",,"['Shapiro, David', 'Bodinayake, Champica K.', 'Nagahawatte, Ajith', 'Devasiri, Vasantha', 'Kurukulasooriya, Ruvini', 'Hsiang, Jeremy', 'Nicholson, Bradley', 'De Silva, Aruna Dharshan', 'Østbye, Truls', 'Reller, Megan E.', 'Woods, Christopher W.', 'Tillekeratne, L. Gayani']",,,,
,PMC,Diagnostic Ophthalmology,,PMC5394613,,,,,"['Sandmeyer, Lynne S.', 'Gagnon, Jerome', 'Bauer, Bianca S.']",,,,
,PMC,Lessons learned from the evolution of terrestrial animal health surveillance in Canada and options for creating a new collaborative national structure,,PMC5394601,,,,,"['Lees, V. Wayne', 'Prince, Cameron']",,,,
,PMC,Other PHAC publications,,PMC5650023,,,,,,,,,
,PMC,The National Ebola Training and Education Center: Preparing the United States for Ebola and Other Special Pathogens,http://dx.doi.org/10.1089/hs.2017.0005,PMC6532632,,,"The National Ebola Training and Education Center (NETEC) was established in 2015 in response to the 2014–2016 Ebola virus disease outbreak in West Africa. The US Department of Health and Human Services office of the Assistant Secretary for Preparedness and Response and the US Centers for Disease Control and Prevention sought to increase the competency of healthcare and public health workers, as well as the capability of healthcare facilities in the United States, to deliver safe, efficient, and effective care to patients infected with Ebola and other special pathogens nationwide. NYC Health + Hospitals/Bellevue, Emory University, and the University of Nebraska Medical Center/Nebraska Medicine were awarded this cooperative agreement, based in part on their experience in safely and successfully evaluating and treating patients with Ebola virus disease in the United States. In 2016, NETEC received a supplemental award to expand on 3 initial primary tasks: (1) develop metrics and conduct peer review assessments; (2) develop and provide educational materials, resources, and tools, including exercise design templates; (3) provide expert training and technical assistance; and, to add a fourth task, create a special pathogens clinical research network.",,"['Kratochvil, Christopher J.', 'Evans, Laura', 'Ribner, Bruce S.', 'Lowe, John J.', 'Cole Harvey, Melissa', 'Hunt, Richard C.', 'Tumpey, Abbigail J.', 'Fagan, Ryan P.', 'Schwedhelm, Michelle M.', 'Bell, Sonia', 'Maher, John', 'Kraft, Colleen S.', 'Cagliuso, Nicholas V.', 'Vanairsdale, Sharon', 'Vasa, Angela', 'Smith, Philip W.']",,,,
,PMC,To what extent are Arab pilgrims to Makkah aware of the middle east respiratory syndrome coronavirus and the precautions against it?,http://dx.doi.org/10.4103/2230-8229.205119,PMC5426109,28566972,CC BY-NC-SA,"BACKGROUND: Approximately, 80% of the many cases of the Middle East respiratory syndrome coronavirus (MERS-CoV) confirmed worldwide were diagnosed in the Kingdom of Saudi Arabia (KSA). The risk of the disease spreading internationally is especially worrying given the role of KSA as the home of the most important Islamic pilgrimage sites. This means the need to assess Arab pilgrims' awareness of MERS-CoV is of paramount importance. MATERIALS AND METHODS: A cross-sectional study was carried out during Ramadan 2015 in the Holy Mosque in Makkah, Saudi Arabia. Self-administered questionnaires were distributed to 417 Arab participants at King Fahad Extension, King Abdullah Prayer Extension and, King Abdullah Piazza Extension after Taraweeh and Fajr prayers. RESULTS: The mean MERS-CoV knowledge score was 52.56. Majority of the respondents (91.3%) were familiar with MERS-CoV. Saudis had significantly higher knowledge of MERS-CoV than non-Saudis (56.92 ± 18.55 vs. 44.91 ± 25.46, p = 0.001). Females had significantly more knowledge about consanguineous MERS-CoV than males (55.82 ± 19.35 vs. 49.93 ± 23.66, p = 0.006). The average knowledge was significantly higher in respondents who had received health advice on MERS-CoV (56.08 ± 20.86 vs. 50.65 ± 22.51, p = 0.024). With respect to stepwise linear regression, knowledge of MERS-CoV tended to increase by 14.23 (B = 14.23%, p = 0.001) in participants who were familiar with MERS-CoV, and by 8.50 (B = 8.50, p = 0.001) in those who perceived MERS-CoV as a very serious disease. CONCLUSION: There is a great need for educational programs to increase awareness about MERS-CoV.",2017 May-Aug,"['Alotaibi, Meshaal S.', 'Alsubaie, Abdulaziz M.', 'Almohaimede, Khaled A.', 'Alotaibi, Turki A.', 'Alharbi, Omar A.', 'Aljadoa, Abdulrahman F.', 'Alhamad, Abdulaziz H.', 'Barry, Mazin']",J Family Community Med,,,
,PMC,Enterovirus 71 suppresses interferon responses by blocking Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling through inducing karyopherin-α1 degradation,http://dx.doi.org/10.1074/jbc.M116.745729,PMC5473229,,,"Enterovirus 71 (EV71) has emerged as one of the most important enteroviruses since the eradication of poliovirus, and it causes severe neurological symptoms for which no effective antiviral drugs are available. Type I interferons (IFN) α/β have been used clinically as antiviral therapy as the first line of defense against virus infections successfully for decades. However, treatment with type I interferons has not been effective in patients with EV71 infection. In this study, we found that in cells pretreated with IFN-β, EV71 infection could still lead to a cytopathic effect, and the viral replication was not affected. The mechanism by which EV71 antagonizes interferon signaling, however, has been controversial. Our study indicated that EV71 infection did not inhibit phosphorylation of STAT1/2 induced by IFN-β stimulation, but p-STAT1/2 transport into the nucleus was significantly blocked. We showed that EV71 infection reduced the formation of STAT/karyopherin-α1 (KPNA1) complex upon interferon stimulation and that the virus down-regulated the expression of KPNA1, a nuclear localization signal receptor for p-STAT1. Using specific caspase inhibitors and siRNA for caspase-3, we demonstrated that EV71 infection induced degradation of cellular KPNA1 in a caspase-3-dependent manner, which led to decreased induction of interferon-inducible genes and IFN response. Viral 2A and 3C proteases did not degrade KPNA1, inhibit the activity of ISRE or suppress the transcription of interferon-inducible genes induced by IFN-β. Our study demonstrates a novel mechanism by which antiviral signaling is suppressed through degradation of KPNA1 by activated caspase-3 induced in an enteroviral infection.",,"['Wang, Chunyang', 'Sun, Menghuai', 'Yuan, Xinhui', 'Ji, Lianfu', 'Jin, Yu', 'Cardona, Carol J.', 'Xing, Zheng']",,,,
,PMC,Porcine Deltacoronavirus nsp5 Antagonizes Type I Interferon Signaling by Cleaving STAT2,http://dx.doi.org/10.1128/JVI.00003-17,PMC5411617,,,"Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus. The first outbreak of PDCoV was announced from the United States in 2014, followed by reports in Asia. The nonstructural protein nsp5 is a 3C-like protease of coronavirus, and our previous study showed that PDCoV nsp5 inhibits type I interferon (IFN) production. In this study, we found that PDCoV nsp5 significantly inhibited IFN-stimulated response element (ISRE) promoter activity and transcription of IFN-stimulated genes (ISGs), suggesting that PDCoV nsp5 also suppresses IFN signaling. Detailed analysis showed that nsp5 cleaved signal transducer and activator of transcription 2 (STAT2) but not Janus kinase 1 (JAK1), tyrosine kinase 2 (TYK2), STAT1, and interferon regulatory factor 9 (IRF9), key molecules of the JAK-STAT pathway. STAT2 cleavage was dependent on the protease activity of nsp5. Interestingly, nsp5 cleaved STAT2 at two sites, glutamine 685 (Q685) and Q758, and similar cleavage was observed in PDCoV-infected cells. As expected, cleaved STAT2 impaired the ability to induce ISGs, demonstrating that STAT2 cleavage is an important mechanism utilized by PDCoV nsp5 to antagonize IFN signaling. We also discussed the substrate selection and binding mode of PDCoV nsp5 by homologous modeling of PDCoV nsp5 with the two cleaved peptide substrates. The results of our study demonstrate that PDCoV nsp5 antagonizes type I IFN signaling by cleaving STAT2 and provides structural insights for comprehending the cleavage mechanism of PDCoV nsp5, revealing a potential new function for PDCoV nsp5 in type I IFN signaling. IMPORTANCE The 3C-like protease encoded by nsp5 is a major protease of coronaviruses; thus, it is an attractive target for development of anticoronavirus drugs. Previous studies have revealed that the 3C-like protease of coronaviruses, including PDCoV and porcine epidemic diarrhea virus (PEDV), antagonizes type I IFN production by targeting the NF-κB essential modulator (NEMO). Here, for the first time, we demonstrate that overexpression of PDCoV nsp5 also antagonizes IFN signaling by cleaving STAT2, an essential component of transcription factor complex ISGF3, and that PDCoV infection reduces the levels of STAT2, which may affect the innate immune response.",,"['Zhu, Xinyu', 'Wang, Dang', 'Zhou, Junwei', 'Pan, Ting', 'Chen, Jiyao', 'Yang, Yuting', 'Lv, Mengting', 'Ye, Xu', 'Peng, Guiqing', 'Fang, Liurong', 'Xiao, Shaobo']",,,,
,PMC,Tight Junction Protein Occludin Is a Porcine Epidemic Diarrhea Virus Entry Factor,http://dx.doi.org/10.1128/JVI.00202-17,PMC5411586,,,"Porcine epidemic diarrhea virus (PEDV), the causative agent of porcine epidemic diarrhea, has caused huge economic losses in pig-producing countries. Although PEDV was long believed to replicate in the intestinal epithelium by using aminopeptidase N as a receptor, the mechanisms of PEDV infection are not fully characterized. In this study, we found that PEDV infection of epithelial cells results in disruption of the tight junctional distribution of occludin to its intracellular location. Overexpression of occludin in target cells makes them more susceptible to PEDV infection, whereas ablation of occludin expression by use of small interfering RNA (siRNA) in target cells significantly reduces their susceptibility to virus infection. However, the results observed with occludin siRNA indicate that occludin is not required for virus attachment. We conclude that occludin plays an essential role in PEDV infection at the postbinding stages. Furthermore, we observed that macropinocytosis inhibitors blocked occludin internalization and virus entry, indicating that virus entry and occludin internalization are closely coupled. However, the macropinocytosis inhibitors could not impede virus replication once the virus had entered host cells. This suggests that occludin internalization by macropinocytosis or a macropinocytosis-like process is involved in the virus entry events. Immunofluorescence confocal microscopy showed that PEDV was trapped at cellular junctional regions upon macropinocytosis inhibitor treatment, indicating that occludin may serve as a scaffold in the vicinity of virus entry. Collectively, these data show that occludin plays an essential role in PEDV infection during late entry events. Our observation may provide novel insights into PEDV infection and related pathogenesis. IMPORTANCE Tight junctions are highly specialized membrane domains whose main function is to attach adjacent cells to each other, thereby forming intercellular seals. Here we investigate, for the first time, the role of the tight junction protein occludin in PEDV infection. We observed that PEDV infection induced the internalization of occludin. By using genetic modification methods, we demonstrate that occludin plays an essential role in PEDV infection. Moreover, PEDV entry and occludin internalization seem to be closely coupled. Our findings reveal a new mechanism of PEDV infection.",,"['Luo, Xiaolei', 'Guo, Longjun', 'Zhang, Jian', 'Xu, Yunfei', 'Gu, Weihong', 'Feng, Li', 'Wang, Yue']",,,,
,PMC,Strategies in Ebola virus disease (EVD) diagnostics at the point of care,http://dx.doi.org/10.1080/1040841X.2017.1313814,PMC5653233,,,"Ebola virus disease (EVD) is a devastating, highly infectious illness with a high mortality rate. The disease is endemic to regions of Central and West Africa, where there is limited laboratory infrastructure and trained staff. The recent 2014 West African EVD outbreak has been unprecedented in case numbers and fatalities, and has proven that such regional outbreaks can become a potential threat to global public health, as it became the source for the subsequent transmission events in Spain and the USA. The urgent need for rapid and affordable means of detecting Ebola is crucial to control the spread of EVD and prevent devastating fatalities. Current diagnostic techniques include molecular diagnostics and other serological and antigen detection assays; which can be time-consuming, laboratory-based, often require trained personnel and specialized equipment. In this review, we discuss the various Ebola detection techniques currently in use, and highlight the potential future directions pertinent to the development and adoption of novel point-of-care diagnostic tools. Finally, a case is made for the need to develop novel microfluidic technologies and versatile rapid detection platforms for early detection of EVD.",,"['Coarsey, Chad T.', 'Esiobu, Nwadiuto', 'Narayanan, Ramswamy', 'Pavlovic, Mirjana', 'Shafiee, Hadi', 'Asghar, Waseem']",,,,
,PMC,Reactivity of Porcine Epidemic Diarrhea Virus Structural Proteins to Antibodies against Porcine Enteric Coronaviruses: Diagnostic Implications,http://dx.doi.org/10.1128/JCM.02507-16,PMC5405260,,,"The development of porcine epidemic diarrhea virus (PEDV) antibody-based assays is important for detecting infected animals, confirming previous virus exposure, and monitoring sow herd immunity. However, the potential cross-reactivity among porcine coronaviruses is a major concern for the development of pathogen-specific assays. In this study, we used serum samples (n = 792) from pigs of precisely known infection status and a multiplex fluorescent microbead-based immunoassay and/or enzyme-linked immunoassay platform to characterize the antibody response to PEDV whole-virus (WV) particles and recombinant polypeptides derived from the four PEDV structural proteins, i.e., spike (S), nucleocapsid (N), membrane (M), and envelope (E). Antibody assay cutoff values were selected to provide 100% diagnostic specificity for each target. The earliest IgG antibody response, mainly directed against S1 polypeptides, was observed at days 7 to 10 postinfection. With the exception of nonreactive protein E, we observed similar antibody ontogenies and patterns of seroconversion for S1, N, M, and WV antigens. Recombinant S1 provided the best diagnostic sensitivity, regardless of the PEDV strain, with no cross-reactivity detected against transmissible gastroenteritis virus (TGEV), porcine respiratory coronavirus (PRCV), or porcine deltacoronavirus (PDCoV) pig antisera. The WV particles showed some cross-reactivity to TGEV Miller and TGEV Purdue antisera, while N protein presented some cross-reactivity to TGEV Miller. The M protein was highly cross-reactive to TGEV and PRCV antisera. Differences in the antibody responses to specific PEDV structural proteins have important implications in the development and performance of antibody assays for the diagnosis of PEDV enteric disease.",,"['Gimenez-Lirola, Luis Gabriel', 'Zhang, Jianqiang', 'Carrillo-Avila, Jose Antonio', 'Chen, Qi', 'Magtoto, Ronaldo', 'Poonsuk, Korakrit', 'Baum, David H.', 'Piñeyro, Pablo', 'Zimmerman, Jeffrey']",,,,
,PMC,IFITM3 inhibits virus-triggered induction of type I interferon by mediating autophagosome-dependent degradation of IRF3,http://dx.doi.org/10.1038/cmi.2017.15,PMC6203713,,,"Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that can be induced by viral infection and interferons (IFNs). It inhibits the entry and replication of many viruses, which are independent of receptor usage but dependent on processes that occur in endosomes. In this study, we demonstrate that IFITM3 plays important roles in regulating the RNA-virus-triggered production of IFN-β in a negative-feedback manner. Overexpression of IFITM3 inhibited Sendai virus-triggered induction of IFN-β, whereas knockdown of IFITM3 had the opposite effect. We also showed that IFITM3 was constitutively associated with IRF3 and regulated the homeostasis of IRF3 by mediating the autophagic degradation of IRF3. These findings suggest a novel inhibitory function of IFITM3 on the RNA-virus-triggered production of type I IFNs and cellular antiviral responses.",,"['Jiang, Li-Qun', 'Xia, Tian', 'Hu, Yun-Hong', 'Sun, Ming-Shun', 'Yan, Shuang', 'Lei, Cao-Qi', 'Shu, Hong-Bing', 'Guo, Ji-Hua', 'Liu, Yu']",,,,
,PMC,Does the impact of biodiversity differ between emerging and endemic pathogens? The need to separate the concepts of hazard and risk,http://dx.doi.org/10.1098/rstb.2016.0129,PMC5413877,,,"Biodiversity is of critical value to human societies, but recent evidence that biodiversity may mitigate infectious-disease risk has sparked controversy among researchers. The majority of work on this topic has focused on direct assessments of the relationship between biodiversity and endemic-pathogen prevalence, without disentangling intervening mechanisms; thus study outcomes often differ, fuelling more debate. Here, we suggest two critical changes to the approach researchers take to understanding relationships between infectious disease, both endemic and emerging, and biodiversity that may help clarify sources of controversy. First, the distinct concepts of hazards versus risks need to be separated to determine how biodiversity and its drivers may act differently on each. This distinction is particularly important since it illustrates that disease emergence drivers in humans could be quite different to the general relationship between biodiversity and transmission of endemic pathogens. Second, the interactive relationship among biodiversity, anthropogenic change and zoonotic disease risk, including both direct and indirect effects, needs to be recognized and accounted for. By carefully disentangling these interactions between humans' activities and pathogen circulation in wildlife, we suggest that conservation efforts could mitigate disease risks and hazards in novel ways that complement more typical disease control efforts. This article is part of the themed issue ‘Conservation, biodiversity and infectious disease: scientific evidence and policy implications’.",,"['Hosseini, Parviez R.', 'Mills, James N.', 'Prieur-Richard, Anne-Hélène', 'Ezenwa, Vanessa O.', 'Bailly, Xavier', 'Rizzoli, Annapaola', 'Suzán, Gerardo', 'Vittecoq, Marion', 'García-Peña, Gabriel E.', 'Daszak, Peter', 'Guégan, Jean-François', 'Roche, Benjamin']",,,,
,PMC,Flex-nucleoside analogues - novel therapeutics against filoviruses,http://dx.doi.org/10.1016/j.bmcl.2017.04.069,PMC5626011,,,"Fleximers, a novel type of flexible nucleoside that have garnered attention due to their unprecedented activity against human coronaviruses, have now exhibited highly promising levels of activity against filoviruses. The Flex-nucleoside was the most potent inhibitor against recombinant Ebola virus in Huh7 cells with an EC(50) = 2 μM, while the McGuigan prodrug was most active against Sudan virus-infected HeLa cells with an EC(50) of 7 μM.",,"['Yates, Mary K.', 'Raje, Mithun R.', 'Chatterjee, Payel', 'Spiropoulou, Christina F.', 'Bavari, Sina', 'Flint, Mike', 'Soloveva, Veronica', 'Seley-Radtke, Katherine L.']",,,,
,PMC,Structural insights into the interaction of coronavirus papain-like proteases and interferon-stimulated gene product 15 from different species,http://dx.doi.org/10.1016/j.jmb.2017.04.011,PMC5634334,,,"Severe Acute and Middle East Respiratory syndrome coronaviruses (SARS-CoV and MERS-CoV) encode multifunctional papain-like proteases (PLPs) that have the ability to process the viral polyprotein to facilitate RNA replication as well as antagonize the host innate-immune response. The latter function involves reversing post-translational modification of cellular proteins conjugated with either ubiquitin (Ub) or Ub-like interferon stimulated gene product 15 (ISG15). Ubiquitin is known to be highly conserved among eukaryotes but surprisingly ISG15 is highly divergent among animals. The ramifications of this sequence divergence to recognition of ISG15 by coronaviral papain-like protease at the structural and biochemical levels are poorly understood. Therefore, the activity of PLPs from SARS-CoV, MERS-CoV and mouse hepatitis virus (MHV) was evaluated against seven ISG15s originating from an assortment of animal species susceptible, and not, to certain coronavirus infections. Excitingly, our kinetic, thermodynamic and structural analysis revealed an array of different preferences among PLPs. Included in these studies is the first insight into a coronoavirus PLP’s interface with ISG15 via SARS-CoV PLP in complex with the principle binding domain of human and mouse ISG15s. The first X-ray structure of the full-length mouse ISG15 protein is also reported and highlights a unique, twisted-hinge region of ISG15 that is not conserved in human ISG15 suggesting a potential role in differential recognition. Taken together, this new information provides a structural and biochemical understanding of the distinct specificities amongst coronavirus PLPs observed and addresses a critical gap of how PLPs can interact with ISG15s from a wide variety of species.",,"['Daczkowski, Courtney M.', 'Dzimianski, John V.', 'Clasman, Jozlyn R.', 'Goodwin, Octavia', 'Mesecar, Andrew D.', 'Pegan, Scott D.']",,,,
,PMC,Evaluation of a Live Attenuated Human Metapneumovirus Vaccine in Adults and Children,http://dx.doi.org/10.1093/jpids/pix006,PMC6075531,,,"We conducted a phase I clinical trial of an experimental live attenuated recombinant human metapneumovirus (HMPV) vaccine (rHMPV-Pa) sequentially in adults, HMPV-seropositive children, and HMPV-seronegative children, the target population for vaccination. rHMPV-Pa was appropriately restricted in replication in adults and HMPV-seropositive children but was overattenuated for HMPV-seronegative children.",,"['Karron, Ruth A', 'San Mateo, Jocelyn', 'Wanionek, Kimberli', 'Collins, Peter L', 'Buchholz, Ursula J']",,,,
,PMC,Structural basis for dimerization and RNA binding of avian infectious bronchitis virus nsp9,http://dx.doi.org/10.1002/pro.3150,PMC5405427,,,"The potential for infection by coronaviruses (CoVs) has become a serious concern with the recent emergence of Middle East respiratory syndrome and severe acute respiratory syndrome (SARS) in the human population. CoVs encode two large polyproteins, which are then processed into 15–16 nonstructural proteins (nsps) that make significant contributions to viral replication and transcription by assembling the RNA replicase complex. Among them, nsp9 plays an essential role in viral replication by forming a homodimer that binds single‐stranded RNA. Thus, disrupting nsp9 dimerization is a potential anti‐CoV therapy. However, different nsp9 dimer forms have been reported for alpha‐ and beta‐CoVs, and no structural information is available for gamma‐CoVs. Here we determined the crystal structure of nsp9 from the avian infectious bronchitis virus (IBV), a representative gamma‐CoV that affects the economy of the poultry industry because it can infect domestic fowl. IBV nsp9 forms a homodimer via interactions across a hydrophobic interface, which consists of two parallel alpha helices near the carboxy terminus of the protein. The IBV nsp9 dimer resembles that of SARS‐CoV nsp9, indicating that this type of dimerization is conserved among all CoVs. This makes disruption of the dimeric interface an excellent strategy for developing anti‐CoV therapies. To facilitate this effort, we characterized the roles of six conserved residues on this interface using site‐directed mutagenesis and a multitude of biochemical and biophysical methods. We found that three residues are critical for nsp9 dimerization and its abitlity to bind RNA.",,"['Hu, Tingting', 'Chen, Cheng', 'Li, Huiyan', 'Dou, Yanshu', 'Zhou, Ming', 'Lu, Deren', 'Zong, Qi', 'Li, Yulei', 'Yang, Cheng', 'Zhong, Zhihui', 'Singh, Namit', 'Hu, Honggang', 'Zhang, Rundong', 'Yang, Haitao', 'Su, Dan']",,,,
,PMC,A CRISPR toolbox to study virus–host interactions,http://dx.doi.org/10.1038/nrmicro.2017.29,PMC5800792,,,"Viruses depend on their hosts to complete their replication cycles; they exploit cellular receptors for entry and hijack cellular functions to replicate their genome, assemble progeny virions and spread. Recently, genome-scale CRISPR–Cas screens have been used to identify host factors that are required for virus replication, including the replication of clinically relevant viruses such as Zika virus, West Nile virus, dengue virus and hepatitis C virus. In this Review, we discuss the technical aspects of genome-scale knockout screens using CRISPR–Cas technology, and we compare these screens with alternative genetic screening technologies. The relative ease of use and reproducibility of CRISPR–Cas make it a powerful tool for probing virus–host interactions and for identifying new antiviral targets.",,"['Puschnik, Andreas S.', 'Majzoub, Karim', 'Ooi, Yaw Shin', 'Carette, Jan E.']",,,,
,PMC,Structure and characterization of a class 3B proline utilization A: Ligand-induced dimerization and importance of the C-terminal domain for catalysis,http://dx.doi.org/10.1074/jbc.M117.786855,PMC5465489,,,"The bifunctional flavoenzyme proline utilization A (PutA) catalyzes the two-step oxidation of proline to glutamate using separate proline dehydrogenase (PRODH) and l-glutamate-γ-semialdehyde dehydrogenase active sites. Because PutAs catalyze sequential reactions, they are good systems for studying how metabolic enzymes communicate via substrate channeling. Although mechanistically similar, PutAs vary widely in domain architecture, oligomeric state, and quaternary structure, and these variations represent different structural solutions to the problem of sequestering a reactive metabolite. Here, we studied PutA from Corynebacterium freiburgense (CfPutA), which belongs to the uncharacterized 3B class of PutAs. A 2.7 Å resolution crystal structure showed the canonical arrangement of PRODH, l-glutamate-γ-semialdehyde dehydrogenase, and C-terminal domains, including an extended interdomain tunnel associated with substrate channeling. The structure unexpectedly revealed a novel open conformation of the PRODH active site, which is interpreted to represent the non-activated conformation, an elusive form of PutA that exhibits suboptimal channeling. Nevertheless, CfPutA exhibited normal substrate-channeling activity, indicating that it isomerizes into the active state under assay conditions. Sedimentation-velocity experiments provided insight into the isomerization process, showing that CfPutA dimerizes in the presence of a proline analog and NAD(+). These results are consistent with the morpheein model of enzyme hysteresis, in which substrate binding induces conformational changes that promote assembly of a high-activity oligomer. Finally, we used domain deletion analysis to investigate the function of the C-terminal domain. Although this domain contains neither catalytic residues nor substrate sites, its removal impaired both catalytic activities, suggesting that it may be essential for active-site integrity.",,"['Korasick, David A.', 'Gamage, Thameesha T.', 'Christgen, Shelbi', 'Stiers, Kyle M.', 'Beamer, Lesa J.', 'Henzl, Michael T.', 'Becker, Donald F.', 'Tanner, John J.']",,,,
,PMC,Development of an intradermal DNA vaccine delivery strategy to achieve single-dose immunity against respiratory syncytial virus,http://dx.doi.org/10.1016/j.vaccine.2017.04.008,PMC5814302,,,"Respiratory syncytial virus (RSV) is a massive medical burden in infants, children and the elderly worldwide, and an effective, safe RSV vaccine remains an unmet need. Here we assess a novel vaccination strategy based on the intradermal delivery of a SynCon(®) DNA-based vaccine encoding engineered RSV-F using a surface electroporation device (SEP) to target epidermal cells, in clinically relevant experimental models. We demonstrate the ability of this strategy to elicit robust immune responses. Importantly we demonstrate complete resistance to pulmonary infection at a single low dose of vaccine in the cotton rat RSV/A challenge model. In contrast to the formalin-inactivated RSV (FI-RSV) vaccine, there was no enhanced lung inflammation upon virus challenge after DNA vaccination. In summary the data presented outline the pre-clinical development of a highly efficacious, tolerable and safe non-replicating vaccine delivery strategy.",,"['Smith, Trevor RF', 'Schultheis, Katherine', 'Morrow, Matthew P', 'Kraynyak, Kimberly A', 'McCoy, Jay R', 'Yim, Kevin C', 'Muthumani, Karuppiah', 'Humeau, Laurent', 'Weiner, David B', 'Sardesai, Niranjan Y', 'Broderick, Kate E']",,,,
,PMC,Comparison of three rapid influenza diagnostic tests with digital readout systems and one conventional rapid influenza diagnostic test,http://dx.doi.org/10.1002/jcla.22234,PMC6817280,,,"BACKGROUND: Rapid influenza diagnostic tests (RIDTs) show variable sensitivities in clinical settings. We aimed to compare three digital RIDTs and one conventional RIDT. METHODS: We assessed 218 nasopharyngeal swabs from patients between neonates and 90 years old in 2016. Three digital RIDTs were BUDDI, Sofia Influenza A+B Fluorescence Immunoassay, Veritor System Flu A+B assay. One conventional test was the SD Bioline Influenza Ag A/B/A(H1N1/2009). All test results were compared with those from the Anyplex Flu A/B Typing Real‐time Detection real‐time PCR. The four RIDTs were tested with diluted solutions from the National Institute for Biological Standards and Control (NIBSC) to compare lower detection limit. Cross‐reactivity of four RIDTs within other respiratory viruses was identified. RESULTS: For influenza A, BUDDI, Sofia, Veritor, and Bioline showed 87.7%, 94.5%, 87.7%, and 72.6% sensitivity, and 100%, 97.7%, 96.5%, and 100% specificity. For influenza B, BUDDI, Sofia, Veritor, and Bioline showed 81.7%, 91.7%, 81.7%, and 78.3% sensitivity, and 100%, 95.3%, 100%, and 100% specificity, respectively. Each RIDT could detect diluted NIBSC solution, according to the level of dilution and specific influenza subtypes. Cross‐reactivity of four RIDTs with other respiratory viruses was not noted. CONCLUSIONS: Sofia showed the highest sensitivity for influenza A and B detection. BUDDI and Veritor showed higher detection sensitivity than a conventional RIDT for influenza A detection, but similar results for influenza B detection. Further study is needed to compare the test performance of RIDTs according to specific, prevalent influenza subtypes.",,"['Ryu, Sook Won', 'Suh, In Bum', 'Ryu, Se‐Min', 'Shin, Kyu Sung', 'Kim, Hyon‐Suk', 'Kim, Juwon', 'Uh, Young', 'Yoon, Kap Jun', 'Lee, Jong‐Han']",,,,
,PMC,A Polymorphism within the Internal Fusion Loop of the Ebola Virus Glycoprotein Modulates Host Cell Entry,http://dx.doi.org/10.1128/JVI.00177-17,PMC5391465,,,"The large scale of the Ebola virus disease (EVD) outbreak in West Africa in 2013-2016 raised the question whether the host cell interactions of the responsible Ebola virus (EBOV) strain differed from those of other ebolaviruses. We previously reported that the glycoprotein (GP) of the virus circulating in West Africa in 2014 (EBOV2014) exhibited reduced ability to mediate entry into two nonhuman primate (NHP)-derived cell lines relative to the GP of EBOV1976. Here, we investigated the molecular determinants underlying the differential entry efficiency. We found that EBOV2014-GP-driven entry into diverse NHP-derived cell lines, as well as human monocyte-derived macrophages and dendritic cells, was reduced compared to EBOV1976-GP, although entry into most human- and all bat-derived cell lines tested was comparable. Moreover, EBOV2014 replication in NHP but not human cells was diminished relative to EBOV1976, suggesting that reduced cell entry translated into reduced viral spread. Mutagenic analysis of EBOV2014-GP and EBOV1976-GP revealed that an amino acid polymorphism in the receptor-binding domain, A82V, modulated entry efficiency in a cell line-independent manner and did not account for the reduced EBOV2014-GP-driven entry into NHP cells. In contrast, polymorphism T544I, located in the internal fusion loop in the GP2 subunit, was found to be responsible for the entry phenotype. These results suggest that position 544 is an important determinant of EBOV infectivity for both NHP and certain human target cells. IMPORTANCE The Ebola virus disease outbreak in West Africa in 2013 entailed more than 10,000 deaths. The scale of the outbreak and its dramatic impact on human health raised the question whether the responsible virus was particularly adept at infecting human cells. Our study shows that an amino acid exchange, A82V, that was acquired during the epidemic and that was not observed in previously circulating viruses, increases viral entry into diverse target cells. In contrast, the epidemic virus showed a reduced ability to enter cells of nonhuman primates compared to the virus circulating in 1976, and a single amino acid exchange in the internal fusion loop of the viral glycoprotein was found to account for this phenotype.",,"['Hoffmann, Markus', 'Crone, Lisa', 'Dietzel, Erik', 'Paijo, Jennifer', 'González-Hernández, Mariana', 'Nehlmeier, Inga', 'Kalinke, Ulrich', 'Becker, Stephan', 'Pöhlmann, Stefan']",,,,
,PMC,"Mutation of the Second Sialic Acid-Binding Site, Resulting in Reduced Neuraminidase Activity, Preceded the Emergence of H7N9 Influenza A Virus",http://dx.doi.org/10.1128/JVI.00049-17,PMC5391454,,,"The emergence of the novel influenza A virus (IAV) H7N9 since 2013 has caused concerns about the ability of the virus to spread between humans. Analysis of the receptor-binding properties of the H7 protein of a human isolate revealed modestly increased binding to α2,6 sialosides and reduced, but still dominant, binding to α2,3-linked sialic acids (SIAs) compared to a closely related avian H7N9 virus from 2008. Here, we show that the corresponding N9 neuraminidases (NAs) display equal enzymatic activities on a soluble monovalent substrate and similar substrate specificities on a glycan array. In contrast, solid-phase activity and binding assays demonstrated reduced specific activity and decreased binding of the novel N9 protein. Mutational analysis showed that these differences resulted from substitution T401A in the 2nd SIA-binding site, indicating that substrate binding via this site enhances NA catalytic activity. Substitution T401A in the novel N9 protein appears to functionally mimic the substitutions that are found in the 2nd SIA-binding site of NA proteins of avian-derived IAVs that became human pandemic viruses. Our phylogenetic analyses show that substitution T401A occurred prior to substitutions in hemagglutinin (HA), causing the altered receptor-binding properties mentioned above. Hence, in contrast to the widespread assumption that such changes in NA are obtained only after acquisition of functional changes in HA, our data indicate that mutations in the 2nd SIA-binding site may have enabled and even driven the acquisition of altered HA receptor-binding properties and may have contributed to the spread of the novel H7N9 viruses. IMPORTANCE Novel H7N9 IAVs continue to cause human infections and pose an ongoing public health threat. Here, we show that their N9 proteins display reduced binding to and lower enzymatic activity against multivalent substrates, resulting from mutation of the 2nd sialic acid-binding site. This mutation preceded and may have driven the selection of substitutions in H7 that modify H7 receptor-binding properties. Of note, all animal IAVs that managed to cross the host species barrier and became human viruses carry mutated 2nd sialic acid-binding sites. Screening of animal IAVs to monitor their potential to cross the host species barrier should therefore focus not only on the HA protein, but also on the functional properties of NA.",,"['Dai, Meiling', 'McBride, Ryan', 'Dortmans, Jos C. F. M.', 'Peng, Wenjie', 'Bakkers, Mark J. G.', 'de Groot, Raoul J.', 'van Kuppeveld, Frank J. M.', 'Paulson, James C.', 'de Vries, Erik', 'de Haan, Cornelis A. M.']",,,,
,PMC,Procalcitonin as a Marker of Etiology in Adults Hospitalized With Community-Acquired Pneumonia,http://dx.doi.org/10.1093/cid/cix317,PMC5850442,,,"BACKGROUND. Recent trials suggest procalcitonin-based guidelines can reduce antibiotic use for respiratory infections. However, the accuracy of procalcitonin to discriminate between viral and bacterial pneumonia requires further dissection. METHODS. We evaluated the association between serum procalcitonin concentration at hospital admission with pathogens detected in a multicenter prospective surveillance study of adults hospitalized with community-acquired pneumonia. Systematic pathogen testing included cultures, serology, urine antigen tests, and molecular detection. Accuracy of procalcitonin to discriminate between viral and bacterial pathogens was calculated. RESULTS. Among 1735 patients, pathogens were identified in 645 (37%), including 169 (10%) with typical bacteria, 67 (4%) with atypical bacteria, and 409 (24%) with viruses only. Median procalcitonin concentration was lower with viral pathogens (0.09 ng/mL; interquartile range [IQR], <0.05–0.54 ng/mL) than atypical bacteria (0.20 ng/mL; IQR, <0.05–0.87 ng/mL; P = .05), and typical bacteria (2.5 ng/mL; IQR, 0.29–12.2 ng/mL; P < .01). Procalcitonin discriminated bacterial pathogens, including typical and atypical bacteria, from viral pathogens with an area under the receiver operating characteristic (ROC) curve of 0.73 (95% confidence interval [CI], .69–.77). A procalcitonin threshold of 0.1 ng/mL resulted in 80.9% (95% CI, 75.3%–85.7%) sensitivity and 51.6% (95% CI, 46.6%–56.5%) specificity for identification of any bacterial pathogen. Procalcitonin discriminated between typical bacteria and the combined group of viruses and atypical bacteria with an area under the ROC curve of 0.79 (95% CI, .75–.82). CONCLUSIONS. No procalcitonin threshold perfectly discriminated between viral and bacterial pathogens, but higher procalcitonin strongly correlated with increased probability of bacterial pathogens, particularly typical bacteria.",,"['Self, Wesley H.', 'Balk, Robert A.', 'Grijalva, Carlos G.', 'Williams, Derek J.', 'Zhu, Yuwei', 'Anderson, Evan J.', 'Waterer, Grant W.', 'Courtney, D. Mark', 'Bramley, Anna M.', 'Trabue, Christopher', 'Fakhran, Sherene', 'Blaschke, Anne J.', 'Jain, Seema', 'Edwards, Kathryn M.', 'Wunderink, Richard G.']",,,,
,PMC,Phylogenetic analysis of avian infectious bronchitis virus isolates from Morocco: a retrospective study (1983 to 2014),http://dx.doi.org/10.1007/s12250-016-3885-3,PMC6598899,,,,,"['Fellahi, Siham', 'El Harrak, Mehdi', 'Khayi, Slimane', 'Guerin, Jean-Luc', 'Kuhn, Jens H.', 'El Houadfi, Mohammed', 'Ennaji, My Mustapha', 'Ducatez, Mariette']",,,,
,PMC,PNAS Plus Significance Statements,http://dx.doi.org/10.1073/pnas.ss11415,PMC5393212,,,,,,,,,
,PMC,Vaccine testing for emerging infections: the case for individual randomisation,http://dx.doi.org/10.1136/medethics-2015-103220,PMC5577361,,,"During the 2014–2015 Ebola outbreak in Guinea, Liberia and Sierra Leone, many opposed the use of individually randomised controlled trials to test candidate Ebola vaccines. For a raging fatal disease, they explained, it is unethical to relegate some study participants to control arms. In Zika and future emerging infections, similar opposition may hinder urgent vaccine research, so it is best to address these questions now. This article lays out the ethical case for individually randomised control in testing vaccines against many emerging infections, including lethal infections in low-income countries, even when at no point in the trial do the controls receive the countermeasures being tested. When individual randomisation is feasible—and it often will be—it tends to save more lives than alternative designs would. And for emerging infections, individual randomisation also tends as such to improve care, access to the experimental vaccine and prospects for all participants relative to their opportunities absent the trial, and no less than alternative designs would. That obtains even under placebo control and without equipoise—requiring which would undermine individual randomisation and the alternative designs that opponents proffered. Our arguments expound four often-neglected factors: benefits to non-participants, benefits to participants once a trial is over including post-trial access to the study intervention, participants’ prospects before randomisation to arms and the near-inevitable disparity between arms in any randomised controlled trial.",,"['Eyal, Nir', 'Lipsitch, Marc']",,,,
,PMC,Emerging infectious diseases: A proactive approach,http://dx.doi.org/10.1073/pnas.1701410114,PMC5402424,,,"Infectious diseases are now emerging or reemerging almost every year. This trend will continue because a number of factors, including the increased global population, aging, travel, urbanization, and climate change, favor the emergence, evolution, and spread of new pathogens. The approach used so far for emerging infectious diseases (EIDs) does not work from the technical point of view, and it is not sustainable. However, the advent of platform technologies offers vaccine manufacturers an opportunity to develop new vaccines faster and to reduce the investment to build manufacturing facilities, in addition to allowing for the possible streamlining of regulatory processes. The new technologies also make possible the rapid development of human monoclonal antibodies that could become a potent immediate response to an emergency. So far, several proposals to approach EIDs have been made independently by scientists, the private sector, national governments, and international organizations such as the World Health Organization (WHO). While each of them has merit, there is a need for a global governance that is capable of taking a strong leadership role and making it attractive to all partners to come to the same table and to coordinate the global approach.",,"['Bloom, David E.', 'Black, Steven', 'Rappuoli, Rino']",,,,
,PMC,CD11c-expressing cells affect Treg behavior in the meninges during CNS infection(),http://dx.doi.org/10.4049/jimmunol.1601581,PMC5451665,,,"Treg cells play an important role in the CNS during multiple infections as well as autoimmune inflammation, but the behavior of this cell type in the CNS has not been explored. In mice, infection with Toxoplasma gondii leads to a Th1-polarized parasite-specific effector T cell response in the brain. Similarly, the Treg cells in the CNS during T. gondii infection are Th1-polarized, exemplified by T-bet, CXCR3, and IFN-γ expression. Unlike effector CD4(+) T cells, an MHC Class II tetramer reagent specific for T. gondii did not recognize Treg cells isolated from the CNS. Likewise, TCR sequencing revealed minimal overlap in TCR sequence between effector and regulatory T cells in the CNS. Whereas effector T cells are found in the brain parenchyma where parasites are present, Treg cells were restricted to the meninges and perivascular spaces. The use of intravital imaging revealed that activated CD4(+) T cells within the meninges were highly migratory, while Treg cells moved more slowly and were found in close association with CD11c(+) cells. To test whether the behavior of Tregs in the meninges is influenced by interactions with CD11c(+) cells, mice were treated with anti-LFA-1 antibodies to reduce the number of CD11c(+) cells in this space. The anti-LFA-1 treatment led to fewer contacts between Tregs and the remaining CD11c(+) cells and increased the speed of Treg cell migration. These data suggest that Treg cells are anatomically restricted within the CNS and the interaction with CD11c(+) populations regulates their local behavior during T. gondii infection.",,"['O’Brien, Carleigh A.', 'Overall, Christopher', 'Konradt, Christoph', 'O’Hara Hall, Aisling C.', 'Hayes, Nikolas W.', 'Wagage, Sagie', 'John, Beena', 'Christian, David A.', 'Hunter, Christopher A.', 'Harris, Tajie H.']",,,,
,PMC,Engineering self-assembled materials to study and direct immune function,http://dx.doi.org/10.1016/j.addr.2017.03.005,PMC6262758,,,"The immune system is an awe-inspiring control structure that maintains a delicate and constantly changing balance between pro-immune functions that fight infection and cancer, regulatory or suppressive functions involved in immune tolerance, and homeostatic resting states. These activities are determined by integrating signals in space and time; thus, improving control over the densities, combinations, and durations with which immune signals are delivered is a central goal to better combat infectious disease, cancer, and autoimmunity. Self-assembly presents a unique opportunity to synthesize materials with well-defined compositions and controlled physical arrangement of molecular building blocks. This review highlights strategies exploiting these capabilities to improve the understanding of how precisely-displayed cues interact with immune cells and tissues. We present work centered on fundamental properties that regulate the nature and magnitude of immune response, highlight pre-clinical and clinical applications of self-assembled technologies in vaccines, cancer, and autoimmunity, and describe some of the key manufacturing and regulatory hurdles facing these areas.",,"['Tostanoski, Lisa H.', 'Jewell, Christopher M.']",,,,
,PMC,Clinical Manifestations Associated with Peripheral Joint Involvement in Patients with Acute Chikungunya Virus Infection,http://dx.doi.org/10.4269/ajtmh.16-0890,PMC5392642,,,"Chikungunya virus (CHIKV) causes an acute febrile illness usually accompanied by severe polyarthralgia and polyarthritis. Previous studies have shown that older age, female gender, and some comorbid conditions are associated with chronic CHIKV arthritis. However, the factors associated with acute arthralgia and arthritis are not well known. Thus, we studied the clinical manifestations associated with acute peripheral joint involvement in a group of CHIKV patients from Puerto Rico. Patients with a history of fever for < 7 days evaluated at the emergency department of a university-based hospital were tested for several pathogens including CHIKV. All patients with laboratory-positive CHIKV infection were studied. Demographic features, clinical manifestations, and comorbidities were determined. Patients with and without peripheral joint involvement were compared using bivariable and multivariable analyses. In total, 172 patients with CHIKV fever were evaluated; 52.9% were women. The mean (standard deviation) age was 21.1 years (19.3). Peripheral arthralgia and/or arthritis were seen in 156 (90.7%) patients. In the multivariable analysis adjusted for age and gender, peripheral joint involvement was associated with myalgia (odds ratio [OR] = 4.65, 95% confidence interval [CI] = 1.48–14.72), back pain (OR = 16.77, 95% CI = 3.07–313.82), ocular pain (OR = 8.88, 95% CI = 1.65–165.19), headache (OR = 3.63, 95% CI = 1.06–12.53), anorexia (OR = 5.68, 95% CI = 1.87–18.97), and nausea (OR = 6.88, 95% CI = 2.05–31.49). In conclusion, in this population of patients with acute CHIKV infection, peripheral joint involvement was associated with myalgia and back pain as well as nonmusculoskeletal manifestations such as headache, ocular pain, anorexia, and nausea.",,"['Arroyo-Ávila, Mariangelí', 'Cabán, Amanda', 'García-Rivera, Enid J.', 'Irizarry-Pérez, Marisela', 'Torres, Hilda', 'Gorbea, Héctor', 'Vilá, Luis M.']",,,,
,PMC,Efficacy of antibody-based therapies against Middle East respiratory syndrome coronavirus (MERS-CoV) in common marmosets,http://dx.doi.org/10.1016/j.antiviral.2017.03.025,PMC6957253,,,"Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to be identified and with a lack of effective clinical treatment and no preventative strategies, treatment using convalescent plasma or monoclonal antibodies (mAbs) is a potential quick route to an intervention. Passive immunotherapy via either convalescent plasma or mAbs has proven to be effective for other infectious agents. Following infection with MERS-CoV, common marmosets were treated with high titer hyperimmune plasma or the mAb m336, at 6 and 48 h post inoculation. Both treatments reduced signs of clinical disease, but reduction in viral loads in the respiratory tract were only found in the hyperimmune plasma group. A decrease in gross pathology was found only in the mAb-treated group, but no histological differences were observed between treated and control animals. While both hyperimmune plasma and the m336 treatments reduced the severity of disease in the common marmoset, neither treatment resulted in full protection against disease.",,"['van Doremalen, Neeltje', 'Falzarano, Darryl', 'Ying, Tianlei', 'de Wit, Emmie', 'Bushmaker, Trenton', 'Feldmann, Friederike', 'Okumura, Atsushi', 'Wang, Yanping', 'Scott, Dana P.', 'Hanley, Patrick W.', 'Feldmann, Heinz', 'Dimitrov, Dimiter S.', 'Munster, Vincent J.']",,,,
,PMC,The Role of Epidermal Growth Factor Receptor (EGFR) Signaling in SARS Coronavirus-Induced Pulmonary Fibrosis,http://dx.doi.org/10.1016/j.antiviral.2017.03.022,PMC5507769,,,"Many survivors of the 2003 outbreak of severe acute respiratory syndrome (SARS) developed residual pulmonary fibrosis with increased severity seen in older patients. Autopsies of patients that died from SARS also showed fibrosis to varying extents. Pulmonary fibrosis can be occasionally seen as a consequence to several respiratory viral infections but is much more common after a SARS coronavirus (SARS-CoV) infection. Given the threat of future outbreaks of severe coronavirus disease, including Middle East respiratory syndrome (MERS), it is important to understand the mechanisms responsible for pulmonary fibrosis, so as to support the development of therapeutic countermeasures and mitigate sequelae of infection. In this article, we summarize pulmonary fibrotic changes observed after a SARS-CoV infection, discuss the extent to which other respiratory viruses induce fibrosis, describe available animal models to study the development of SARS-CoV induced fibrosis and review evidence that pulmonary fibrosis is caused by a hyperactive host response to lung injury mediated by epidermal growth factor receptor (EGFR) signaling. We summarize work from our group and others indicating that inhibiting EGFR signaling may prevent an excessive fibrotic response to SARS-CoV and other respiratory viral infections and propose directions for future research.",,"['Venkataraman, Thiagarajan', 'Frieman, Matthew B']",,,,
,PMC,Niclosamide: beyond an antihelminthic drug,http://dx.doi.org/10.1016/j.cellsig.2017.04.001,PMC5628105,,,"Niclosamide is an oral antihelminthic drug used to treat parasitic infections in millions of people worldwide. However recent studies have indicated that niclosamide may have broad clinical applications for the treatment of diseases other than those caused by parasites. These diseases and symptoms may include cancer, bacterial and viral infection, metabolic diseases such as Type II diabetes, NASH and NAFLD, artery constriction, endometriosis, neuropathic pain, rheumatoid arthritis, sclerodermatous graft-versus-host disease, systemic sclerosis. Among the underlying mechanisms associated with the drug actions of niclosamide are uncoupling of oxidative phosphorylation, and modulation of Wnt/β-catenin, mTORC1, STAT3, NF-κB and Notch signaling pathways. Here we provide a brief overview of the biological activities of niclosamide, its potential clinical applications, and its challenges for use as a new therapy for systemic diseases.",,"['Chen, Wei', 'Mook, Robert A.', 'Premont, Richard T.', 'Wang, Jiangbo']",,,,
,PMC,Vaccines for epidemic infections and the role of CEPI,http://dx.doi.org/10.1080/21645515.2017.1306615,PMC5718831,,,The author reviews the foundation of the Coalition for Epidemic Preparedness and Innovations and the choices it has made for funding of vaccine development against epidemic diseases. He comments on those decisions as well as proposing how CEPI could remain relevant for the long term.,,"Plotkin, Stanley A.",,,,
,PMC,Sex-based differences in susceptibility to SARS-CoV infection,http://dx.doi.org/10.4049/jimmunol.1601896,PMC5450662,,,"Pathogenic human coronaviruses such as the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) cause acute respiratory illness. Epidemiological data from the 2002-2003 SARS epidemic and recent MERS indicate that there may be sex-dependent differences in disease outcomes. To investigate these differences, we infected male and female mice of different age groups with SARS-CoV and analyzed their susceptibility to the infection. Our results showed that male mice were more susceptible to SARS-CoV infection compared to age matched females. The degree of sex-bias to SARS-CoV infection increased with advancing age such that middle-aged mice showed much more pronounced differences compared to young mice. Enhanced susceptibility of male mice to SARS-CoV was associated with elevated virus titers, enhanced vascular leakage and alveolar edema. These changes were accompanied by increased accumulation of inflammatory monocyte macrophages (IMMs) and neutrophils in the lungs of male mice and depletion of IMMs partially protected these mice from lethal SARS. Moreover, the sex-specific differences were independent of T and B cell responses. Furthermore, ovariectomy or treating female mice with an estrogen receptor antagonist increased mortality indicating a protective effect for estrogen receptor signaling in mice infected with SARS-CoV. Together, these data suggest that sex differences in susceptibility to SARS-CoV in mice parallel those observed in patients and also identify estrogen receptor signaling as critical for protection in females.",,"['Channappanavar, Rudragouda', 'Fett, Craig', 'Mack, Matthias', 'Ten Eyck, Patrick P', 'Meyerholz, David K', 'Perlman, Stanley']",,,,
,PMC,Membrane fission by protein crowding,http://dx.doi.org/10.1073/pnas.1616199114,PMC5402459,,,"Membrane fission, which facilitates compartmentalization of biological processes into discrete, membrane-bound volumes, is essential for cellular life. Proteins with specific structural features including constricting rings, helical scaffolds, and hydrophobic membrane insertions are thought to be the primary drivers of fission. In contrast, here we report a mechanism of fission that is independent of protein structure—steric pressure among membrane-bound proteins. In particular, random collisions among crowded proteins generate substantial pressure, which if unbalanced on the opposite membrane surface can dramatically increase membrane curvature, leading to fission. Using the endocytic protein epsin1 N-terminal homology domain (ENTH), previously thought to drive fission by hydrophobic insertion, our results show that membrane coverage correlates equally with fission regardless of the hydrophobicity of insertions. Specifically, combining FRET-based measurements of membrane coverage with multiple, independent measurements of membrane vesiculation revealed that fission became spontaneous as steric pressure increased. Further, fission efficiency remained equally potent when helices were replaced by synthetic membrane-binding motifs. These data challenge the view that hydrophobic insertions drive membrane fission, suggesting instead that the role of insertions is to anchor proteins strongly to membrane surfaces, amplifying steric pressure. In line with these conclusions, even green fluorescent protein (GFP) was able to drive fission efficiently when bound to the membrane at high coverage. Our conclusions are further strengthened by the finding that intrinsically disordered proteins, which have large hydrodynamic radii yet lack a defined structure, drove fission with substantially greater potency than smaller, structured proteins.",,"['Snead, Wilton T.', 'Hayden, Carl C.', 'Gadok, Avinash K.', 'Zhao, Chi', 'Lafer, Eileen M.', 'Rangamani, Padmini', 'Stachowiak, Jeanne C.']",,,,
,PMC,Using the Upshur principles to discuss medical fitness to drive,,PMC5389751,,,,,"Weir, Erica",,,,
,PMC,Surrogate end points save lives,http://dx.doi.org/10.1503/cjs.013916,PMC5373719,,,"Patient-centric markers are important, and when they can be conveniently measured they should dominate research questions. However, when the research question pertains to serious or potentially fatal illnesses and it will take years or even decades to answer with patient-centric outcomes, then a pragmatic approach based on common sense and surrogate markers should be adopted. This commentary discusses the important role that surrogate markers can play in medical research.",,"Vinden, Christopher",,,,
,PMC,Efficacy of an accelerated hydrogen peroxide disinfectant to inactivate porcine epidemic diarrhea virus in swine feces on metal surfaces,,PMC5370535,,,"In May of 2013, porcine epidemic diarrhea virus (PEDV) was detected in swine for the first time in North America. It spread rapidly, in part due to contaminated livestock trailers. The objective of this study was to test the efficacy of an accelerated hydrogen peroxide disinfectant for inactivating PEDV in the presence of feces on metal surfaces, such as those found in livestock trailers. Three-week-old barrows were inoculated intragastrically with 5 mL of PEDV-negative feces for the negative control, 5 mL of untreated PEDV-positive feces for the positive control, and 5 mL or 10 mL of PEDV-positive feces that was subjected to treatment with a 1:16 or 1:32 concentrations of accelerated hydrogen peroxide disinfectant for a contact time of 30 min at 20°C. These pigs served as a bioassay to determine the infectivity of virus following treatment. Rectal swabs collected from the inoculated pigs on days 3 and 7 post-inoculation were tested by using PEDV-specific real-time reverse transcription polymerase chain reaction and the proportion of pigs in each group that became infected with PEDV was assessed. None of the pigs used for the bioassay in the 4 treatment groups and the negative control group became infected with PEDV, which was significantly different from the positive control group (P < 0.05) in which all pigs were infected. The results suggest that the application of the accelerated hydrogen peroxide under these conditions was sufficient to inactivate the virus in feces found on metal surfaces.",,"['Holtkamp, Derald J.', 'Myers, Jacqueline', 'Thomas, Paul R.', 'Karriker, Locke A.', 'Ramirez, Alejandro', 'Zhang, Jianqiang', 'Wang, Chong']",,,,
,PMC,Effect of Isoflurane Anesthesia on Circadian Metabolism and Physiology in Rats,,PMC5402733,,,"Isoflurane anesthesia alters the blood levels of several neuroendocrine hormones associated with normal metabolism and physiology and increases stress, but the effect of brief CO(2) anesthesia on these parameters is unknown. In this study, we examined the effects of isoflurane (4%) compared with brief CO(2) (70% CO(2), 30% air) anesthesia on circadian rhythms of plasma measures of physiology and metabolism. Adult male Sprague–Dawley rats (Crl:SD; n = 6 per group) were maintained on a 12:12-h light:dark (300 lx; lights on, 0600) photoperiod. After 1 wk of acclimation, a series of 6 low-volume blood draws were collected by cardiocentesis under anesthesia using isoflurane (10 min or less) compared with CO(2) (1 min or less) at a single circadian time point every 4 d (0400, 0800, 1200, 1600, 2000, or 2400) over 3 wk to assess arterial blood glucose, lactic acid, and potassium and plasma melatonin, leptin, insulin, total fatty acids, and corticosterone concentrations. Results revealed that plasma levels (mean ± SEM) of melatonin were low (11 ± 1 pg/mL) during the light phase in both groups but were significantly lower during the dark phase in the isoflurane group (48 ± 6 pg/mL) compared with the CO(2) group (162 ± 18 pg/mL). In addition, prominent circadian rhythms of arterial plasma levels of corticosterone, glucose, total fatty acids, lactic acid, and potassium were altered in the isoflurane group compared with the CO(2) group. These findings demonstrate that the normal circadian rhythms of endocrine physiology and metabolism observed during brief CO(2) anesthesia in rats are markedly disrupted by isoflurane anesthesia.",,"['Wren-Dail, Melissa A', 'Dauchy, Robert T', 'Blask, David E', 'Hill, Steven M', 'Ooms, Tara G', 'Dupepe, Lynell M', 'Bohm, Rudolf P']",,,,
,PMC,Negative regulators of the RIG-I-like receptor signaling pathway,http://dx.doi.org/10.1002/eji.201646484,PMC5554756,,,"Upon recognition of specific molecular patterns on viruses, bacteria and fungi, host cells trigger an innate immune response, which culminates in the production of type I interferons (IFN), pro-inflammatory cytokines and chemokines, and restricts pathogen replication and spread within the host. At each stage of the immune response, there are stimulatory and inhibitory signals that regulate the magnitude, quality, and character of the response. Positive regulation promotes an antiviral state to control and eventually clear infection whereas negative regulation dampens inflammation and prevents immune-mediated tissue damage. An over-exuberant innate immune response can lead to the destruction of cells and tissues, and the development of spontaneous autoimmunity. The RIG-I-like receptors (RLRs) retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) belong to a family of cytosolic host RNA helicases that recognize distinct non-self RNA signatures and trigger innate immune responses against several RNA virus infections. The RLR signaling pathway is tightly regulated to achieve a well-orchestrated response aimed at maximizing antiviral immunity and minimizing immune-mediated pathology. This review highlights contemporary findings on negative regulators of the RLR signaling pathway, with specific focus on the proteins and biological processes that directly regulate RIG-I, MDA5 and MAVS function.",,"['Quicke, Kendra M.', 'Diamond, Michael S.', 'Suthar, Mehul S.']",,,,
,PMC,Public Understanding of Medical Countermeasures,http://dx.doi.org/10.1089/hs.2016.0074,PMC5583561,,,"Medical countermeasures, including new drugs and vaccines, are necessary to protect the public's health from novel diseases and terrorist threats. Experience with the 2001 anthrax attack and the 2009 H1N1 pandemic suggest that there is limited willingness to accept such drugs and that minority groups may respond differently from others. We conducted 148 intercept interviews in the metropolitan Washington, DC, area, examining 2 hypothetical scenarios: a new respiratory virus and public exposure to high levels of radiation. Findings provide insights into key factors that affect whether diverse members of the public comply with recommended protective actions like taking emergency authorized vaccines. These insights can help improve how public health practitioners communicate during uncertain times.",,"['Liu, Brooke Fisher', 'Quinn, Sandra C.', 'Egnoto, Michael', 'Freimuth, Vicki', 'Boonchaisri, Natalie']",,,,
,PMC,Respiratory Multiplex Polymerase Chain Reaction: An Important Diagnostic Tool in Immunocompromised Patients,http://dx.doi.org/10.4103/ijccm.IJCCM_2_17,PMC5416785,28515602,CC BY-NC-SA,"BACKGROUND: Viruses and atypical pathogens can cause significant respiratory illness in immunocompromised patients. Multiplex polymerase chain reaction (MPCR) has improved the diagnostic yield of pathogens, and it is easier to identify the co-infections also. The present study was done to evaluate the performance of MPCR on bronchoalveolar lavage (BAL) samples in immunocompromised patients. METHODS: Atotal of 177 BAL specimens collected over a 19 months period from immunocompromised patients with respiratory illness were analyzed with the MPCR and aerobic culture. Patients were divided into four according to the pathogens. Category V (only viral), Category NV (nonviral, i.e., bacteria and atypical), Category M (mixed, i.e., both viral and nonviral pathogen), and Category UK (unknown etiology). RESULTS: MPCR identified the causative pathogen in 59.3% of patients while culture could identify only in 37.8% of patients. Most frequent etiological agent was Klebsiella pneumoniae (32%), followed by cytomegalovirus (21%), and Pneumocystis jirovecii (10%). Numbers of patients in each category were Category V (9.6%), Category NV (43.5%), Category M (19.8%), and Category UK (27.1%). Mortality was significantly higher in patients of Category M having mixed infections. CONCLUSION: MPCR is highly sensitive and rapid tool which can be considered in the routine diagnostic algorithm of respiratory illness in immunocompromised patients.",2017 Apr,"['Kaur, Amarjeet', 'Kumar, Navin', 'Sengupta, Sharmila', 'Mehta, Yatin']",Indian J Crit Care Med,,,
,PMC,Chasing viruses feverishly,http://dx.doi.org/10.4103/2249-4863.220019,PMC5749054,29302515,CC BY-NC-SA,"A number of viral diseases have emerged and re-emerged in India and globally, in the last few years. Effective prevention and control of these diseases require, in addition to a functioning disease surveillance system, interventions both before and after disease occurrence, and a combination of personal and population services. However, the current efforts to control emerging viral diseases in India has major therapeutic focus (and attention on diagnostic and curative services) and there is limited attention on preventive and promotive components. It is proposed that for an effective and successful control, a systematic approach is adopted with an appropriate selection of personal and population health services, delivered by government through participation of private sector. This is possible through commitment and leadership of Government and other public health agencies, supplemented by multi agency coordination, sufficient funding and an accountability mechanism.",2017 Apr-Jun,"Lahariya, Chandrakant",J Family Med Prim Care,,,
,PMC,"Reflections on the Ebola Public Health Emergency of International Concern, Part 2: The Unseen Epidemic of Posttraumatic Stress among Health-care Personnel and Survivors of the 2014–2016 Ebola Outbreak",http://dx.doi.org/10.4103/jgid.jgid_24_17,PMC5452550,28584454,CC BY-NC-SA,,2017 Apr-Jun,"['Paladino, Lorenzo', 'Sharpe, Richard P', 'Galwankar, Sagar C', 'Sholevar, Farhad', 'Marchionni, Christine', 'Papadimos, Thomas J', 'Paul, Elisabeth', 'Hansoti, Bhakti', 'Firstenberg, Michael', 'Garg, Manish', 'Watson, Mindy', 'Baxter, Ric A', 'Stawicki, Stanislaw P', None]",J Glob Infect Dis,,,
,PMC,Porcine circovirus type 2 capsid protein induces unfolded protein response with subsequent activation of apoptosis,http://dx.doi.org/10.1631/jzus.B1600208,PMC5394096,,,"Porcine circovirus type 2 (PCV2) has recently been reported to elicit the unfolded protein response (UPR) via activation of the PERK/eIF2α (RNA-activated protein kinase-like endoplasmic reticulum (ER) kinase/eukaryotic initiation factor 2α) pathway. This study attempted to examine which viral protein might be involved in inducing UPR and whether this cellular event would lead to apoptosis of the cells expressing the viral protein. By transient expression, we found that both replicase (Rep) and capsid (Cap) proteins of PCV2 could induce ER stress as shown by increased phosphorylation of PERK with subsequent activation of the eIF2α-ATF4 (activating transcription factor 4)-CHOP (CCAAT/enhancer-binding protein homologous protein) axis. Cap expression, but not Rep, significantly reduced anti-apoptotic B-cell lymphoma-2 (Bcl-2) and increased caspase-3 cleavage, possibly due to increased expression of CHOP. Since knockdown of PERK by RNA interference clearly reduced Cap-induced CHOP expression, caspase-3 cleavage, and apoptotic cell death possibly by partially rescuing Bcl-2 expression, we propose that there is connection between Cap-induced UPR and apoptosis via the PERK/eIF2α/ATF4/CHOP/Bcl-2 pathway. This study, together with our earlier studies, provides insight into the mechanisms underlying PCV2 pathogenesis.",,"['Zhou, Ying-shan', 'Gu, Yuan-xing', 'Qi, Bao-zhu', 'Zhang, Yi-kai', 'Li, Xiao-liang', 'Fang, Wei-huan']",,,,
,PMC,NON-ENZYMATIC GLYCATION INTERFERES WITH FIBRONECTIN-INTEGRIN INTERACTIONS IN VASCULAR SMOOTH MUSCLE CELLS,http://dx.doi.org/10.1111/micc.12347,PMC5404995,,,"OBJECTIVE: We aimed to investigate whether advanced non-enzymatic glycation of the extracellular matrix (ECM) protein, fibronectin, impacts its normal integrin-mediated interaction with arteriolar vascular smooth muscle cells (VSMC). METHODS: Atomic force microscopy (AFM) was performed on cultured VSMC from rat cremaster arterioles to study native and glycated fibronectin (FN and gFN) interactions with cellular integrins. AFM probes were functionalized with FN or gFN or with native or glycated albumin (gAlb) as controls. RESULTS: VSMC showed increased adhesion probability to gFN (72.9 ± 3.5 %) compared to native FN (63.0 ± 1.6 %). VSMCs similarly showed increased probability of adhesion (63.8 ± 1.7 %) to gAlb compared to native Alb (40.1 ± 4.7 %). Adhesion of native FN to VSMC was α5 and β1 integrin-dependent whereas adhesion of gFN to VSMC was integrin-independent. The RAGE-selective inhibitor, FPS-ZM1, blocked gFN (and gAlb) adhesion suggesting that adhesion of glycated proteins was RAGE-dependent. Interaction of FN with VSMC was not altered by soluble gFN while soluble native FN did not inhibit adhesion of gFN to VSMC. In contrast, gAlb inhibited adhesion of gFN to VSMC in a concentration-dependent manner. CONCLUSIONS: Glycation of FN shifts the nature of cellular adhesion from integrin- to RAGE-dependent mechanisms.",,"['Dhar, Srijita', 'Sun, Zhe', 'Meininger, Gerald A.', 'Hill, Michael A.']",,,,
,PMC,Oligonucleotide aptamers: potential novel molecules against viral hepatitis,http://dx.doi.org/10.4103/1735-5362.202447,PMC5385733,28515761,CC BY-NC-SA,"Viral hepatitis, as an international public health concern, seriously affects communities and health system. In recent years, great strides have been taken for development of new potential tools against viral hepatitis. Among these efforts, a valuable strategy introduced new molecules called “aptamers”. Aptamers as potential alternatives for antibodies could be directed against any protein in infected cells and any components of viral particles. In this review, we will focus on recent advances in the diagnosis and treatment of viral hepatitis based on aptamer technology. In recent years, various types of aptamers including RNA and DNA were introduced against viral hepatitis. Some of these aptamers can be utilized for early and precise diagnosis of hepatitis infections and other group selected as therapeutic tools against viral targets. Designing diagnostic and therapeutic platforms based on aptamer technology is a promising approach in viral infections. The obtained aptamers in the recent years showed obvious potential for use as diagnostic and therapeutic tools against viral hepatitis. Although some modifications to increase the biostability and half-life of aptamers are underway, it seems these molecules will be a favorable substitute for monoclonal antibody in near future.",2017 Apr,"['Mirian, Mina', 'Khanahmad, Hossein', 'Darzi, Leila', 'Salehi, Mansour', 'Sadeghi-Aliabadi, Hojjat']",Res Pharm Sci,,,
,PMC,Infectious diseases in Singapore and Asia: persistent challenges in a new era,http://dx.doi.org/10.11622/smedj.2017025,PMC5392599,,,,,"Lee, Lawrence Soon-U",,,,
,PMC,Jumping species – A Mechanism for Coronavirus Persistence and Survival,http://dx.doi.org/10.1016/j.coviro.2017.01.002,PMC5474123,,,"Zoonotic transmission of novel viruses represents a significant threat to global public health and is fueled by globalization, the loss of natural habitats, and exposure to new hosts. For coronaviruses (CoVs), broad diversity exists within bat populations and uniquely positions them to seed future emergence events. In this review, we explore the host and viral dynamics that shape these CoV populations for survival, amplification, and possible emergence in novel hosts.",,"['Menachery, Vineet D.', 'Graham, Rachel L.', 'Baric, Ralph S.']",,,,
,PMC,Atypical RNA Elements Modulate Translational Readthrough in Tobacco Necrosis Virus D,http://dx.doi.org/10.1128/JVI.02443-16,PMC5375699,,,"Tobacco necrosis virus, strain D (TNV-D), is a positive-strand RNA virus in the genus Betanecrovirus and family Tombusviridae. The production of its RNA-dependent RNA polymerase, p82, is achieved by translational readthrough. This process is stimulated by an RNA structure that is positioned immediately downstream of the recoding site, termed the readthrough stem-loop (RTSL), and a sequence in the 3′ untranslated region of the TNV-D genome, called the distal readthrough element (DRTE). Notably, a base pairing interaction between the RTSL and the DRTE, spanning ∼3,000 nucleotides, is required for enhancement of readthrough. Here, some of the structural features of the RTSL, as well as RNA sequences and structures that flank either the RTSL or DRTE, were investigated for their involvement in translational readthrough and virus infectivity. The results revealed that (i) the RTSL-DRTE interaction cannot be functionally replaced by stabilizing the RTSL structure, (ii) a novel tertiary RNA structure positioned just 3′ to the RTSL is required for optimal translational readthrough and virus infectivity, and (iii) these same activities also rely on an RNA stem-loop located immediately upstream of the DRTE. Functional counterparts for the RTSL-proximal structure may also be present in other tombusvirids. The identification of additional distinct RNA structures that modulate readthrough suggests that regulation of this process by genomic features may be more complex than previously appreciated. Possible roles for these novel RNA elements are discussed. IMPORTANCE The analysis of factors that affect recoding events in viruses is leading to an ever more complex picture of this important process. In this study, two new atypical RNA elements were shown to contribute to efficient translational readthrough of the TNV-D polymerase and to mediate robust viral genome accumulation in infections. One of the structures, located close to the recoding site, could have functional equivalents in related genera, while the other structure, positioned 3′ proximally in the viral genome, is likely limited to betanecroviruses. Irrespective of their prevalence, the identification of these novel RNA elements adds to the current repertoire of viral genome-based modulators of translational readthrough and provides a notable example of the complexity of regulation of this process.",,"['Newburn, Laura R.', 'White, K. Andrew']",,,,
,PMC,Dinucleotide Composition in Animal RNA Viruses Is Shaped More by Virus Family than by Host Species,http://dx.doi.org/10.1128/JVI.02381-16,PMC5375695,,,"Viruses use the cellular machinery of their hosts for replication. It has therefore been proposed that the nucleotide and dinucleotide compositions of viruses should match those of their host species. If this is upheld, it may then be possible to use dinucleotide composition to predict the true host species of viruses sampled in metagenomic surveys. However, it is also clear that different taxonomic groups of viruses tend to have distinctive patterns of dinucleotide composition that may be independent of host species. To determine the relative strength of the effect of host versus virus family in shaping dinucleotide composition, we performed a comparative analysis of 20 RNA virus families from 15 host groupings, spanning two animal phyla and more than 900 virus species. In particular, we determined the odds ratios for the 16 possible dinucleotides and performed a discriminant analysis to evaluate the capability of virus dinucleotide composition to predict the correct virus family or host taxon from which it was isolated. Notably, while 81% of the data analyzed here were predicted to the correct virus family, only 62% of these data were predicted to their correct subphylum/class host and a mere 32% to their correct mammalian order. Similarly, dinucleotide composition has a weak predictive power for different hosts within individual virus families. We therefore conclude that dinucleotide composition is generally uniform within a virus family but less well reflects that of its host species. This has obvious implications for attempts to accurately predict host species from virus genome sequences alone. IMPORTANCE Determining the processes that shape virus genomes is central to understanding virus evolution and emergence. One question of particular importance is why nucleotide and dinucleotide frequencies differ so markedly between viruses. In particular, it is currently unclear whether host species or virus family has the biggest impact on dinucleotide frequencies and whether dinucleotide composition can be used to accurately predict host species. Using a comparative analysis, we show that dinucleotide composition has a strong phylogenetic association across different RNA virus families, such that dinucleotide composition can predict the family from which a virus sequence has been isolated. Conversely, dinucleotide composition has a poorer predictive power for the different host species within a virus family and across different virus families, indicating that the host has a relatively small impact on the dinucleotide composition of a virus genome.",,"['Di Giallonardo, Francesca', 'Schlub, Timothy E.', 'Shi, Mang', 'Holmes, Edward C.']",,,,
,PMC,Neurovirulent Murine Coronavirus JHM.SD Uses Cellular Zinc Metalloproteases for Virus Entry and Cell-Cell Fusion,http://dx.doi.org/10.1128/JVI.01564-16,PMC5375694,,,"The coronavirus (CoV) S protein requires cleavage by host cell proteases to mediate virus-cell and cell-cell fusion. Many strains of the murine coronavirus mouse hepatitis virus (MHV) have distinct, S-dependent organ and tissue tropisms despite using a common receptor, suggesting that they employ different cellular proteases for fusion. In support of this hypothesis, we found that inhibition of endosomal acidification only modestly decreased entry, and overexpression of the cell surface protease TMPRSS2 greatly enhanced entry, of the highly neurovirulent MHV strain JHM.SD relative to their effects on the reference strain, A59. However, TMPRSS2 overexpression decreased MHV structural protein expression, release of infectious particles, and syncytium formation, and endogenous serine protease activity did not contribute greatly to infection. We therefore investigated the importance of other classes of cellular proteases and found that inhibition of matrix metalloproteinase (MMP)- and a disintegrin and metalloprotease (ADAM)-family zinc metalloproteases markedly decreased both entry and cell-cell fusion. Suppression of virus by metalloprotease inhibition varied among tested cell lines and MHV S proteins, suggesting a role for metalloprotease use in strain-dependent tropism. We conclude that zinc metalloproteases must be considered potential contributors to coronavirus fusion. IMPORTANCE The family Coronaviridae includes viruses that cause two emerging diseases of humans, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), as well as a number of important animal pathogens. Because coronaviruses depend on host protease-mediated cleavage of their S proteins for entry, a number of protease inhibitors have been proposed as antiviral agents. However, it is unclear which proteases mediate in vivo infection. For example, SARS-CoV infection of cultured cells depends on endosomal acid pH-dependent proteases rather than on the cell surface acid pH-independent serine protease TMPRSS2, but Zhou et al. (Antiviral Res 116:76–84, 2015, doi:10.1016/j.antiviral.2015.01.011) found that a serine protease inhibitor was more protective than a cathepsin inhibitor in SARS-CoV-infected mice. This paper explores the contributions of endosomal acidification and various proteases to coronavirus infection and identifies an unexpected class of proteases, the matrix metalloproteinase and ADAM families, as potential targets for anticoronavirus therapy.",,"['Phillips, Judith M.', 'Gallagher, Tom', 'Weiss, Susan R.']",,,,
,PMC,Tumor Necrosis Factor Alpha-Induced Recruitment of Inflammatory Mononuclear Cells Leads to Inflammation and Altered Brain Development in Murine Cytomegalovirus-Infected Newborn Mice,http://dx.doi.org/10.1128/JVI.01983-16,PMC5375689,,,"Congenital human cytomegalovirus (HCMV) infection is a significant cause of abnormal neurodevelopment and long-term neurological sequelae in infants and children. Resident cell populations of the developing brain have been suggested to be more susceptible to virus-induced cytopathology, a pathway thought to contribute to the clinical outcomes following intrauterine HCMV infection. However, recent findings in a newborn mouse model of the infection in the developing brain have indicated that elevated levels of proinflammatory mediators leading to mononuclear cell activation and recruitment could underlie the abnormal neurodevelopment. In this study, we demonstrate that treatment with tumor necrosis factor alpha (TNF-α)-neutralizing antibodies decreased the frequency of CD45(+) Ly6C(hi) CD11b(+) CCR2(+) activated myeloid mononuclear cells (MMCs) and the levels of proinflammatory cytokines in the blood and the brains of murine CMV-infected mice. This treatment also normalized neurodevelopment in infected mice without significantly impacting the level of virus replication. These results indicate that TNF-α is a major component of the inflammatory response associated with altered neurodevelopment that follows murine CMV infection of the developing brain and that a subset of peripheral blood myeloid mononuclear cells represent a key effector cell population in this model of virus-induced inflammatory disease of the developing brain. IMPORTANCE Congenital human cytomegalovirus (HCMV) infection is the most common viral infection of the developing human fetus and can result in neurodevelopmental sequelae. Mechanisms of disease leading to neurodevelopmental deficits in infected infants remain undefined, but postulated pathways include loss of neuronal progenitor cells, damage to the developing vascular system of the brain, and altered cellular positioning. Direct virus-mediated cytopathic effects cannot explain the phenotypes of brain damage in most infected infants. Using a mouse model that recapitulates characteristics of the brain infection described in human infants, we have shown that TNF-α plays a key role in brain inflammation, including recruitment of inflammatory mononuclear cells. Neutralization of TNF-α normalized neurodevelopmental abnormalities in infected mice, providing evidence that virus-induced inflammation is a major component of disease in the developing brain. These results suggest that interventions limiting inflammation associated with the infection could potentially improve the neurologic outcome of infants infected in utero with HCMV.",,"['Seleme, Maria C.', 'Kosmac, Kate', 'Jonjic, Stipan', 'Britt, William J.']",,,,
,PMC,Japanese Encephalitis Virus NS5 Inhibits Type I Interferon (IFN) Production by Blocking the Nuclear Translocation of IFN Regulatory Factor 3 and NF-κB,http://dx.doi.org/10.1128/JVI.00039-17,PMC5375679,,,"The type I interferon (IFN) response is part of the first-line defense against viral infection. To initiate replication, viruses have developed powerful evasion strategies to counteract host IFN responses. In the present study, we found that the Japanese encephalitis virus (JEV) NS5 protein could inhibit double-stranded RNA (dsRNA)-induced IFN-β expression in a dose-dependent manner. Our data further demonstrated that JEV NS5 suppressed the activation of the IFN transcriptional factors IFN regulatory factor 3 (IRF3) and NF-κB. However, there was no defect in the phosphorylation of IRF3 and degradation of IκB, an upstream inhibitor of NF-κB, upon NS5 expression, indicating a direct inhibition of the nuclear localization of IRF3 and NF-κB by NS5. Mechanistically, NS5 was shown to interact with the nuclear transport proteins KPNA2, KPNA3, and KPNA4, which competitively blocked the interaction of KPNA3 and KPNA4 with their cargo molecules, IRF3 and p65, a subunit of NF-κB, and thus inhibited the nuclear translocation of IRF3 and NF-κB. Furthermore, overexpression of KPNA3 and KPNA4 restored the activity of IRF3 and NF-κB and increased the production of IFN-β in NS5-expressing or JEV-infected cells. Additionally, an upregulated replication level of JEV was shown upon KPNA3 or KPNA4 overexpression. These results suggest that JEV NS5 inhibits the induction of type I IFN by targeting KPNA3 and KPNA4. IMPORTANCE JEV is the major cause of viral encephalitis in South and Southeast Asia, with high mortality. However, the molecular mechanisms contributing to the severe pathogenesis are poorly understood. The ability of JEV to counteract the host innate immune response is potentially one of the mechanisms responsible for JEV virulence. Here we demonstrate the ability of JEV NS5 to interfere with the dsRNA-induced nuclear translocation of IRF3 and NF-κB by competitively inhibiting the interaction of IRF3 and NF-κB with nuclear transport proteins. Via this mechanism, JEV NS5 suppresses the induction of type I IFN and the antiviral response in host cells. These findings reveal a novel strategy for JEV to escape the host innate immune response and provide new insights into the pathogenesis of JEV.",,"['Ye, Jing', 'Chen, Zheng', 'Li, Yunchuan', 'Zhao, Zikai', 'He, Wen', 'Zohaib, Ali', 'Song, Yunfeng', 'Deng, Chenglin', 'Zhang, Bo', 'Chen, Huanchun', 'Cao, Shengbo']",,,,
,PMC,"Recombinant Isfahan Virus and Vesicular Stomatitis Virus Vaccine Vectors Provide Durable, Multivalent, Single-Dose Protection against Lethal Alphavirus Challenge",http://dx.doi.org/10.1128/JVI.01729-16,PMC5375677,,,"The demonstrated clinical efficacy of a recombinant vesicular stomatitis virus (rVSV) vaccine vector has stimulated the investigation of additional serologically distinct Vesiculovirus vectors as therapeutic and/or prophylactic vaccine vectors to combat emerging viral diseases. Among these viral threats are the encephalitic alphaviruses Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV), which have demonstrated potential for natural disease outbreaks, yet no licensed vaccines are available in the event of an epidemic. Here we report the rescue of recombinant Isfahan virus (rISFV) from genomic cDNA as a potential new vaccine vector platform. The rISFV genome was modified to attenuate virulence and express the VEEV and EEEV E2/E1 surface glycoproteins as vaccine antigens. A single dose of the rISFV vaccine vectors elicited neutralizing antibody responses and protected mice from lethal VEEV and EEEV challenges at 1 month postvaccination as well as lethal VEEV challenge at 8 months postvaccination. A mixture of rISFV vectors expressing the VEEV and EEEV E2/E1 glycoproteins also provided durable, single-dose protection from lethal VEEV and EEEV challenges, demonstrating the potential for a multivalent vaccine formulation. These findings were paralleled in studies with an attenuated form of rVSV expressing the VEEV E2/E1 glycoproteins. Both the rVSV and rISFV vectors were attenuated by using an approach that has demonstrated safety in human trials of an rVSV/HIV-1 vaccine. Vaccines based on either of these vaccine vector platforms may present a safe and effective approach to prevent alphavirus-induced disease in humans. IMPORTANCE This work introduces rISFV as a novel vaccine vector platform that is serologically distinct and phylogenetically distant from VSV. The rISFV vector has been attenuated by an approach used for an rVSV vector that has demonstrated safety in clinical studies. The vaccine potential of the rISFV vector was investigated in a well-established alphavirus disease model. The findings indicate the feasibility of producing a safe, efficacious, multivalent vaccine against the encephalitic alphaviruses VEEV and EEEV, both of which can cause fatal disease. This work also demonstrates the efficacy of an attenuated rVSV vector that has already demonstrated safety and immunogenicity in multiple HIV-1 phase I clinical studies. The absence of serological cross-reactivity between rVSV and rISFV and their phylogenetic divergence within the Vesiculovirus genus indicate potential for two stand-alone vaccine vector platforms that could be used to target multiple bacterial and/or viral agents in successive immunization campaigns or as heterologous prime-boost agents.",,"['Nasar, Farooq', 'Matassov, Demetrius', 'Seymour, Robert L.', 'Latham, Theresa', 'Gorchakov, Rodion V.', 'Nowak, Rebecca M.', 'Leal, Grace', 'Hamm, Stefan', 'Eldridge, John H.', 'Tesh, Robert B.', 'Clarke, David K.', 'Weaver, Scott C.']",,,,
,PMC,Innate Immune Responses of Bat and Human Cells to Filoviruses: Commonalities and Distinctions,http://dx.doi.org/10.1128/JVI.02471-16,PMC5375674,,,"Marburg (MARV) and Ebola (EBOV) viruses are zoonotic pathogens that cause severe hemorrhagic fever in humans. The natural reservoir of MARV is the Egyptian rousette bat (Rousettus aegyptiacus); that of EBOV is unknown but believed to be another bat species. The Egyptian rousette develops subclinical productive infection with MARV but is refractory to EBOV. Interaction of filoviruses with hosts is greatly affected by the viral interferon (IFN)-inhibiting domains (IID). Our study was aimed at characterization of innate immune responses to filoviruses and the role of filovirus IID in bat and human cells. The study demonstrated that EBOV and MARV replicate to similar levels in all tested cell lines, indicating that permissiveness for EBOV at cell and organism levels do not necessarily correlate. Filoviruses, particularly MARV, induced a potent innate immune response in rousette cells, which was generally stronger than that in human cells. Both EBOV VP35 and VP24 IID were found to suppress the innate immune response in rousette cells, but only VP35 IID appeared to promote virus replication. Along with IFN-α and IFN-β, IFN-γ was demonstrated to control filovirus infection in bat cells but not in human cells, suggesting host species specificity of the antiviral effect. The antiviral effects of bat IFNs appeared not to correlate with induction of IFN-stimulated genes 54 and 56, which were detected in human cells ectopically expressing bat IFN-α and IFN-β. As bat IFN-γ induced the type I IFN pathway, its antiviral effect is likely to be partially induced via cross talk. IMPORTANCE Bats serve as reservoirs for multiple emerging viruses, including filoviruses, henipaviruses, lyssaviruses, and zoonotic coronaviruses. Although there is no evidence for symptomatic disease caused by either Marburg or Ebola viruses in bats, spillover of these viruses into human populations causes deadly outbreaks. The reason for the lack of symptomatic disease in bats infected with filoviruses remains unknown. The outcome of a virus-host interaction depends on the ability of the host immune system to suppress viral replication and the ability of a virus to counteract the host defenses. Our study is a comparative analysis of the host innate immune response to either MARV or EBOV infection in bat and human cells and the role of viral interferon-inhibiting domains in the host innate immune responses. The data are useful for understanding the interactions of filoviruses with natural and accidental hosts and for identification of factors that influence filovirus evolution.",,"['Kuzmin, Ivan V.', 'Schwarz, Toni M.', 'Ilinykh, Philipp A.', 'Jordan, Ingo', 'Ksiazek, Thomas G.', 'Sachidanandam, Ravi', 'Basler, Christopher F.', 'Bukreyev, Alexander']",,,,
,PMC,The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination,http://dx.doi.org/10.1128/JVI.02143-16,PMC5375661,,,"Severe acute respiratory syndrome (SARS) is a respiratory disease, caused by a coronavirus (SARS-CoV), that is characterized by atypical pneumonia. The nucleocapsid protein (N protein) of SARS-CoV plays an important role in inhibition of type I interferon (IFN) production via an unknown mechanism. In this study, the SARS-CoV N protein was found to bind to the SPRY domain of the tripartite motif protein 25 (TRIM25) E3 ubiquitin ligase, thereby interfering with the association between TRIM25 and retinoic acid-inducible gene I (RIG-I) and inhibiting TRIM25-mediated RIG-I ubiquitination and activation. Type I IFN production induced by poly I·C or Sendai virus (SeV) was suppressed by the SARS-CoV N protein. SARS-CoV replication was increased by overexpression of the full-length N protein but not N amino acids 1 to 361, which could not interact with TRIM25. These findings provide an insightful interpretation of the SARS-CoV-mediated host innate immune suppression caused by the N protein. IMPORTANCE The SARS-CoV N protein is essential for the viral life cycle and plays a key role in the virus-host interaction. We demonstrated that the interaction between the C terminus of the N protein and the SPRY domain of TRIM25 inhibited TRIM25-mediated RIG-I ubiquitination, which resulted in the inhibition of IFN production. We also found that the Middle East respiratory syndrome CoV (MERS-CoV) N protein interacted with TRIM25 and inhibited RIG-I signaling. The outcomes of these findings indicate the function of the coronavirus N protein in modulating the host's initial innate immune response.",,"['Hu, Yong', 'Li, Wei', 'Gao, Ting', 'Cui, Yan', 'Jin, Yanwen', 'Li, Ping', 'Ma, Qingjun', 'Liu, Xuan', 'Cao, Cheng']",,,,
,PMC,Comparing nonpharmaceutical interventions for containing emerging epidemics,http://dx.doi.org/10.1073/pnas.1616438114,PMC5393248,,,"Strategies for containing an emerging infectious disease outbreak must be nonpharmaceutical when drugs or vaccines for the pathogen do not yet exist or are unavailable. The success of these nonpharmaceutical strategies will depend on not only the effectiveness of isolation measures but also the epidemiological characteristics of the infection. However, there is currently no systematic framework to assess the relationship between different containment strategies and the natural history and epidemiological dynamics of the pathogen. Here, we compare the effectiveness of quarantine and symptom monitoring, implemented via contact tracing, in controlling epidemics using an agent-based branching model. We examine the relationship between epidemic containment and the disease dynamics of symptoms and infectiousness for seven case-study diseases with diverse natural histories, including Ebola, influenza A, and severe acute respiratory syndrome (SARS). We show that the comparative effectiveness of symptom monitoring and quarantine depends critically on the natural history of the infectious disease, its inherent transmissibility, and the intervention feasibility in the particular healthcare setting. The benefit of quarantine over symptom monitoring is generally maximized for fast-course diseases, but we show the conditions under which symptom monitoring alone can control certain outbreaks. This quantitative framework can guide policymakers on how best to use nonpharmaceutical interventions and prioritize research during an outbreak of an emerging pathogen.",,"['Peak, Corey M.', 'Childs, Lauren M.', 'Grad, Yonatan H.', 'Buckee, Caroline O.']",,,,
,PMC,Mouse-adapted MERS coronavirus causes lethal lung disease in human DPP4 knockin mice,http://dx.doi.org/10.1073/pnas.1619109114,PMC5393213,,,"The Middle East respiratory syndrome (MERS) emerged in Saudi Arabia in 2012, caused by a zoonotically transmitted coronavirus (CoV). Over 1,900 cases have been reported to date, with ∼36% fatality rate. Lack of autopsies from MERS cases has hindered understanding of MERS-CoV pathogenesis. A small animal model that develops progressive pulmonary manifestations when infected with MERS-CoV would advance the field. As mice are restricted to infection at the level of DPP4, the MERS-CoV receptor, we generated mice with humanized exons 10–12 of the mouse Dpp4 locus. Upon inoculation with MERS-CoV, human DPP4 knockin (KI) mice supported virus replication in the lungs, but developed no illness. After 30 serial passages through the lungs of KI mice, a mouse-adapted virus emerged (MERS(MA)) that grew in lungs to over 100 times higher titers than the starting virus. A plaque-purified MERS(MA) clone caused weight loss and fatal infection. Virus antigen was observed in airway epithelia, pneumocytes, and macrophages. Pathologic findings included diffuse alveolar damage with pulmonary edema and hyaline membrane formation associated with accumulation of activated inflammatory monocyte–macrophages and neutrophils in the lungs. Relative to the parental MERS-CoV, MERS(MA) viruses contained 13–22 mutations, including several within the spike (S) glycoprotein gene. S-protein mutations sensitized viruses to entry-activating serine proteases and conferred more rapid entry kinetics. Recombinant MERS(MA) bearing mutant S proteins were more virulent than the parental virus in hDPP4 KI mice. The hDPP4 KI mouse and the MERS(MA) provide tools to investigate disease causes and develop new therapies.",,"['Li, Kun', 'Wohlford-Lenane, Christine L.', 'Channappanavar, Rudragouda', 'Park, Jung-Eun', 'Earnest, James T.', 'Bair, Thomas B.', 'Bates, Amber M.', 'Brogden, Kim A.', 'Flaherty, Heather A.', 'Gallagher, Tom', 'Meyerholz, David K.', 'Perlman, Stanley', 'McCray, Paul B.']",,,,
,PMC,On doing the right science,http://dx.doi.org/10.1080/21645515.2017.1293948,PMC5404358,,,,,"Crowcroft, Natasha Sarah",,,,
,PMC,Clinical Features of Human Metapneumovirus Infection in Ambulatory Children Aged 5–13 Years,http://dx.doi.org/10.1093/jpids/pix012,PMC5954304,,,"We detected human metapneumovirus (HMPV) in 54 (5%) of 1055 children aged 5 to 13 years with acute respiratory illness (ARI) identified by outpatient and emergency department surveillance between November and May 2003–2009. Its clinical features were similar to those of HMPV-negative ARI, except a diagnosis of pneumonia was more likely (13% vs 4%, respectively; P = .005) and a diagnosis of pharyngitis (7% vs 24%, respectively; P = .005) was less likely in patients with HMPV- positive ARI than those with HMPV-negative ARI.",,"['Howard, Leigh M', 'Edwards, Kathryn M', 'Zhu, Yuwei', 'Griffin, Marie R', 'Weinberg, Geoffrey A', 'Szilagyi, Peter G', 'Staat, Mary A', 'Payne, Daniel C', 'Williams, John V']",,,,
,PMC,A Special Issue for The 13th Annual Conference of the Taiwan Society for Mass Spectrometry,http://dx.doi.org/10.5702/massspectrometry.K0010,PMC5448329,,,,,"['Liao, Pao-Chi', 'Shiea, Jentaie']",,,,
,PMC,The answer is blowing in the wind: an uncommon cause for severe ARDS accompanied by circulatory insufficiency requiring extracorporeal membrane oxygenation,http://dx.doi.org/10.1136/bcr-2016-218079,PMC5372129,,,"We report a rare complication in an immunosuppressed patient with IgA nephropathy who suffered from severe acute respiratory distress syndrome, severe capillary leakage and shock after placement of a double lumen central venous catheter. He could be successfully treated by extracorporeal membrane oxygenation (ECMO) and therapeutic plasma exchange. This report highlights the severity of late-onset complications of catheter placements and shows the potential of ECMO treatment for the management of acute illnesses with bridge to recovery.",,"['Einecke, Gunilla', 'Beutel, Gernot', 'Hoeper, Marius M', 'Kielstein, Jan T']",,,,
,PMC,The hidden treasure in your data: phasing with unexpected weak anomalous scatterers from routine data sets,http://dx.doi.org/10.1107/S2053230X17002680,PMC5379167,,,"Single-wavelength anomalous dispersion (SAD) utilizing anomalous signal from native S atoms, or other atoms with Z ≤ 20, generally requires highly redundant data collected using relatively long-wavelength X-rays. Here, the results from two proteins are presented where the anomalous signal from serendipitously acquired surface-bound Ca atoms with an anomalous data multiplicity of around 10 was utilized to drive de novo structure determination. In both cases, the Ca atoms were acquired from the crystallization solution, and the data-collection strategy was not optimized to exploit the anomalous signal from these scatterers. The X-ray data were collected at 0.98 Å wavelength in one case and at 1.74 Å in the other (the wavelength was optimized for sulfur, but the anomalous signal from calcium was exploited for structure solution). Similarly, using a test case, it is shown that data collected at ∼1.0 Å wavelength, where the f′′ value for sulfur is 0.28 e, are sufficient for structure determination using intrinsic S atoms from a strongly diffracting crystal. Interestingly, it was also observed that SHELXD was capable of generating a substructure solution from high-exposure data with a completeness of 70% for low-resolution reflections extending to 3.5 Å resolution with relatively low anomalous multiplicity. Considering the fact that many crystallization conditions contain anomalous scatterers such as Cl, Ca, Mn etc., checking for the presence of fortuitous anomalous signal in data from well diffracting crystals could prove useful in either determining the structure de novo or in accurately assigning surface-bound atoms.",,"['Hegde, Raghurama P.', 'Fedorov, Alexander A.', 'Sauder, J. Michael', 'Burley, Stephen K.', 'Almo, Steven C.', 'Ramagopal, Udupi A.']",,,,
,PMC,Structure of the infectious salmon anemia virus receptor complex illustrates a unique binding strategy for attachment,http://dx.doi.org/10.1073/pnas.1617993114,PMC5389325,,,"Orthomyxoviruses are an important family of RNA viruses, which include the various influenza viruses. Despite global efforts to eradicate orthomyxoviral pathogens, these infections remain pervasive. One such orthomyxovirus, infectious salmon anemia virus (ISAV), spreads easily throughout farmed and wild salmonids, constituting a significant economic burden. ISAV entry requires the interplay of the virion-attached hemagglutinin-esterase and fusion glycoproteins. Preventing infections will rely on improved understanding of ISAV entry. Here, we present the crystal structures of ISAV hemagglutinin-esterase unbound and complexed with receptor. Several distinctive features observed in ISAV HE are not seen in any other viral glycoprotein. The structures reveal a unique mode of receptor binding that is dependent on the oligomeric assembly of hemagglutinin-esterase. Importantly, ISAV hemagglutinin-esterase receptor engagement does not initiate conformational rearrangements, suggesting a distinct viral entry mechanism. This work improves our understanding of ISAV pathogenesis and expands our knowledge on the overall diversity of viral glycoprotein-mediated entry mechanisms. Finally, it provides an atomic-resolution model of the primary neutralizing antigen critical for vaccine development.",,"['Cook, Jonathan D.', 'Sultana, Azmiri', 'Lee, Jeffrey E.']",,,,
,PMC,Antiviral Lectins: Selective Inhibitors of Viral Entry,http://dx.doi.org/10.1016/j.antiviral.2017.03.007,PMC5414728,,,"Many natural lectins have been reported to have antiviral activity. As some of these have been put forward as potential development candidates for preventing or treating viral infections, we have set out in this review to survey the literature on antiviral lectins. The review groups lectins by structural class and class of source organism we also detail their carbohydrate specificity and their reported antiviral activities. The review concludes with a brief discussion of several of the pertinent hurdles that heterologous proteins must clear to be useful clinical candidates and cites examples where such studies have been reported for antiviral lectins. Though the clearest path currently being followed is the use of antiviral lectins as anti-HIV microbicides via topical mucosal administration, some investigators have also found systemic efficacy against acute infections following subcutaneous administration.",,"['Mitchell, Carter A.', 'Ramessar, Koreen', 'O’Keefe, Barry R.']",,,,
,PMC,In vitro and in vivo Safety Evaluation of Nephure(TM),http://dx.doi.org/10.1016/j.yrtph.2017.03.016,PMC5500298,,,"Nephure(TM) is a proprietary oxalate decarboxylase (OxDC) enzyme being developed as a food ingredient. In this study, the safety of Nephure(TM) was evaluated in a bacterial mutagenicity assay and in a sub-chronic (13-week) oral toxicity study in rats. Nephure(TM) did not show any mutagenic properties in the mutagenicity assay. In the 13-week sub-chronic oral toxicity study in which 10 Sprague Dawley rats per sex were administered 0, 118, 235 and 475 mg/kg bw/day (8260, 16450 and 33,250 Units/kg bw/day, respectively) of Nephure(TM) by gavage, male and female rats did not show any test article-related clinical observations or effects on body weight, body weight gain, food consumption, food efficiency, ophthalmology, functional observational battery parameters or motor activity. Furthermore, there were no changes in coagulation, clinical chemistry, urinalysis or hematology parameters, macroscopic/microscopic findings or organ weights that could be attributed to the test article. Based on these results, Nephure(TM) was not mutagenic and the no-adverse-effect level (NOAEL) in the 13-week study was determined to be 475 mg/kg bw/day (33,250 Units/kg bw/day). Evaluation of the estimated consumption of Nephure(TM), generation of the metabolite formate, and the current safety studies resulted in a conclusion of a tolerable upper limit of 3450 Units of OxDC activity/day (57.5 Units activity/kg bw/day), when Nephure(TM) is added to food to decrease dietary oxalate.",,"['Cowley, Helena', 'Yan, Qin', 'Koetzner, Lee', 'Dolan, Laurie', 'Nordwald, Erik', 'Cowley, Aaron B.']",,,,
,PMC,Within host RNA virus persistence: mechanisms and consequences,http://dx.doi.org/10.1016/j.coviro.2017.03.001,PMC5474179,,,"In a prototypical response to an acute viral infection it would be expected that the adaptive immune response would eliminate all virally infected cells within a few weeks of infection. However many (non-retrovirus) RNA viruses can establish “within host” persistent infections that occasionally lead to chronic or reactivated disease. Despite the importance of “within host” persistent RNA virus infections, much has still to be learnt about the molecular mechanisms by which RNA viruses establish persistent infections, why innate and adaptive immune responses fail to rapidly clear these infections, and the epidemiological and potential disease consequences of such infections.",,"['Randall, Richard E.', 'Griffin, Diane E.']",,,,
,PMC,"Cross-sectional surveillance of Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels and other mammals in Egypt, August 2015 to January 2016",http://dx.doi.org/10.2807/1560-7917.ES.2017.22.11.30487,PMC5356426,28333616,CC BY,"A cross-sectional study was conducted in Egypt to determine the prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) in imported and resident camels and bats, as well as to assess possible transmission of the virus to domestic ruminants and equines. A total of 1,031 sera, 1,078 nasal swabs, 13 rectal swabs, and 38 milk samples were collected from 1,078 camels in different types of sites. In addition, 145 domestic animals and 109 bats were sampled. Overall, of 1,031 serologically-tested camels, 871 (84.5%) had MERS-CoV neutralising antibodies. Seroprevalence was significantly higher in imported (614/692; 88.7%) than resident camels (257/339; 5.8%) (p < 0.05). Camels from Sudan (543/594; 91.4%) had a higher seroprevalence than those from East Africa (71/98; 72.4%) (p < 0.05). Sampling site and age were also associated with MERS-CoV seroprevalence (p < 0.05). All tested samples from domestic animals and bats were negative for MERS-CoV antibodies except one sheep sample which showed a 1:640 titre. Of 1,078 camels, 41 (3.8%) were positive for MERS-CoV genetic material. Sequences obtained were not found to cluster with clade A or B MERS-CoV sequences and were genetically diverse. The presence of neutralising antibodies in one sheep apparently in contact with seropositive camels calls for further studies on domestic animals in contact with camels.",2017 Mar 16,"['Ali, Mohamed', 'El-Shesheny, Rabeh', 'Kandeil, Ahmed', 'Shehata, Mahmoud', 'Elsokary, Basma', 'Gomaa, Mokhtar', 'Hassan, Naglaa', 'El Sayed, Ahmed', 'El-Taweel, Ahmed', 'Sobhy, Heba', 'Oludayo, Fasina Folorunso', 'Dauphin, Gwenaelle', 'El Masry, Ihab', 'Wolde, Abebe Wossene', 'Daszak, Peter', 'Miller, Maureen', 'VonDobschuetz, Sophie', 'Gardner, Emma', 'Morzaria, Subhash', 'Lubroth, Juan', 'Makonnen, Yilma Jobre']",Euro Surveill,,,
,PMC,Serum IFN-γ–induced protein 10 (IP-10) as a biomarker for severity of acute respiratory infection in healthy adults,http://dx.doi.org/10.1016/j.jcv.2017.03.003,PMC5408957,,,"BACKGROUND: The inflammatory chemokine, interferon-gamma inducible protein of 10 kDa (IP-10), is a biomarker associated with several conditions. OBJECTIVES: This study investigated serum concentrations of IP-10 in healthy individuals who developed acute respiratory infection (ARI). The hypothesis is that serum IP-10 concentrations correlate with ARI severity and detection of viral pathogens. STUDY DESIGN: Data come from a randomized controlled trial measuring the effects of mindfulness meditation or exercise on ARI (Clinical Trials ID: NCT01654289). Healthy adults ages 30–69 were followed for a single season for ARI incidence and severity. This trial is ongoing, and the investigators are still blinded. When a participant reported ARI symptoms, nasal swab and lavage for PCR-based viral identification and blood samples were collected within the first 72 hours of ARI symptoms. Serum IP-10 concentrations were measured by ELISA (R&D Systems, Inc. Quantikine ELISA, Minneapolis, MN). ARI severity was measured using the validated Wisconsin Upper Respiratory Symptom Survey (WURSS-24) until the ARI episode resolved. RESULTS: Serum IP-10 concentrations from 225 ARI episodes correlated with ARI global severity (rho 0.28 [95% CI: 0.15–0.39]; p<0.001). IP-10 concentrations were higher with an ARI in which a viral pathogen was detected compared to no viral pathogen detected (median 366 pg/ml [IQR: 227–486] vs 163 pg/ml [IQR: 127–295], p<0.0001). Influenza infections had higher IP-10 concentrations than coronavirus, enterovirus or rhinovirus, and paramyxovirus. CONCLUSION: Serum IP-10 concentration correlates with ARI global severity. Also, IP-10 concentration measured early in the course of the ARI correlates with the daily severity, duration, and illness symptoms.",,"['Hayney, Mary S.', 'Henriquez, Kelsey M.', 'Barnet, Jodi H.', 'Ewers, Tola', 'Champion, Heather M.', 'Flannery, Sean', 'Barrett, Bruce']",,,,
,PMC,microRNA-1246 mediates lipopolysaccharide-induced pulmonary endothelial cell apoptosis and acute lung injury by targeting angiotensin-converting enzyme 2,,PMC5376019,,,"In this study, we aimed to identify potential microRNA (miRNA) regulators of angiotensin-converting enzyme 2 (ACE2) and to explore their roles in lipopolysaccharide (LPS)-induced acute lung injury (ALI). The expression of predicted miRNA regulators of ACE2 was examined in LPS-exposed pulmonary microvascular endothelial cells (PMVECs). Gain- and loss-of-function studies were performed to determine the functions of candidate miRNAs in LPS-induced PMVEC apoptosis and inflammatory response. The roles of the miRNAs in LPS-induced lung inflammation and permeability were investigated in a mouse model. Notably, LPS (1 μg/mL) significantly induced the expression of miR-1246 in PMVECs. ACE2 was validated as a target gene of miR-1246. Silencing of miR-1246 prevented LPS-induced inhibition of ACE2, which was accompanied by reduced apoptosis and production of IL-1β and TNF-α. In contrast, ectopic expression of miR-1246 triggered apoptosis in PMVECs and promoted IL-1β and TNF-α release. MiR-1246-mediated apoptosis of PMVECs was impaired by overexpression of ACE2. Depletion of miR-1246 attenuated lung inflammation, neutrophil infiltration, and vascular permeability and restored pulmonary expression of ACE2 in LPS-exposed mice. Taken together, miR-1246 meditates LPS-induced pulmonary endothelial cell apoptosis in vitro and ALI in mouse models, which are, at least partially, ascribed to repression of ACE2.",,"['Fang, Yue', 'Gao, Fengying', 'Hao, Jing', 'Liu, Zhenwei']",,,,
,PMC,Modeling month-season of birth as a risk factor in mouse models of chronic disease: from multiple sclerosis to autoimmune encephalomyelitis,http://dx.doi.org/10.1096/fj.201700062,PMC5434654,,,"Month-season of birth (M-SOB) is a risk factor in multiple chronic diseases, including multiple sclerosis (MS), where the lowest and greatest risk of developing MS coincide with the lowest and highest birth rates, respectively. To determine whether M-SOB effects in such chronic diseases as MS can be experimentally modeled, we examined the effect of M-SOB on susceptibility of C57BL/6J mice to experimental autoimmune encephalomyelitis (EAE). As in MS, mice that were born during the M-SOB with the lowest birth rate were less susceptible to EAE than mice born during the M-SOB with the highest birth rate. We also show that the M-SOB effect on EAE susceptibility is associated with differential production of multiple cytokines/chemokines by neuroantigen-specific T cells that are known to play a role in EAE pathogenesis. Taken together, these results support the existence of an M-SOB effect that may reflect seasonally dependent developmental differences in adaptive immune responses to self-antigens independent of external stimuli, including exposure to sunlight and vitamin D. Moreover, our documentation of an M-SOB effect on EAE susceptibility in mice allows for modeling and detailed analysis of mechanisms that underlie the M-SOB effect in not only MS but in numerous other diseases in which M-SOB impacts susceptibility.—Reynolds, J. D., Case, L. K., Krementsov, D. N., Raza, A., Bartiss, R., Teuscher, C. Modeling month-season of birth as a risk factor in mouse models of chronic disease: from multiple sclerosis to autoimmune encephalomyelitis.",,"['Reynolds, Jacob D.', 'Case, Laure K.', 'Krementsov, Dimitry N.', 'Raza, Abbas', 'Bartiss, Rose', 'Teuscher, Cory']",,,,
,PMC,DNA Vaccine Encoding Middle East Respiratory Syndrome Coronavirus S1 Protein Induces Protective Immune Responses in Mice,http://dx.doi.org/10.1016/j.vaccine.2017.02.063,PMC5411280,,,"The Middle East respiratory syndrome coronavirus (MERS-CoV), is an emerging pathogen that continues to cause outbreaks in the Arabian peninsula and in travelers from this region, raising the concern that a global pandemic could occur. Here, we show that a DNA vaccine encoding the first 725 amino acids (S1) of MERS-CoV spike (S) protein induces antigen-specific humoral and cellular immune responses in mice. With three immunizations, high titers of neutralizing antibodies (up to 1: 10(4)) were generated without adjuvant. DNA vaccination with the MERS-CoV S1 gene markedly increased the frequencies of antigen-specific CD4(+) and CD8(+) T cells secreting IFN-γ and other cytokines. Both pcDNA3.1-S1 DNA vaccine immunization and passive transfer of immune serum from pcDNA3.1-S1 vaccinated mice protected Ad5-hDPP4-transduced mice from MERS-CoV challenge. These results demonstrate that a DNA vaccine encoding MERS-CoV S1 protein induces strong protective immune responses against MERS-CoV infection.",,"['Chi, Hang', 'Zheng, Xuexing', 'Wang, Xiwen', 'Wang, Chong', 'Wang, Hualei', 'Gai, Weiwei', 'Perlman, Stanley', 'Yang, Songtao', 'Zhao, Jincun', 'Xia, Xianzhu']",,,,
,PMC,WHO veteran heads up Canadian public health,http://dx.doi.org/10.1503/cmaj.1095394,PMC5359114,,,,,"Brown, Carolyn",,,,
,PMC,"Contribution of type III interferons to antiviral immunity: location, location, location",http://dx.doi.org/10.1074/jbc.R117.777102,PMC5418032,,,"Type I interferons (IFN-α/β) and the more recently identified type III IFNs (IFN-λ) function as the first line of defense against virus infection and regulate the development of both innate and adaptive immune responses. Type III IFNs were originally identified as a novel ligand-receptor system acting in parallel with type I IFNs, but subsequent studies have provided increasing evidence for distinct roles for each IFN family. In addition to their compartmentalized antiviral actions, these two systems appear to have multiple levels of cross-regulation and act coordinately to achieve effective antimicrobial protection with minimal collateral damage to the host.",,"['Kotenko, Sergei V.', 'Durbin, Joan E.']",,,,
,PMC,Mutagen resistance and mutation restriction of St. Louis encephalitis virus,http://dx.doi.org/10.1099/jgv.0.000682,PMC6537618,,,"The error rate of the RNA-dependent RNA polymerase (RdRp) of RNA viruses is important in maintaining genetic diversity for viral adaptation and fitness. Numerous studies have shown that mutagen-resistant RNA virus variants display amino acid mutations in the RdRp and other replicase subunits, which in turn exhibit an altered fidelity phenotype affecting viral fitness, adaptability and pathogenicity. St. Louis encephalitis virus (SLEV), like its close relative West Nile virus, is a mosquito-borne flavivirus that has the ability to cause neuroinvasive disease in humans. Here, we describe the successful generation of multiple ribavirin-resistant populations containing a shared amino acid mutation in the SLEV RdRp (E416K). These E416K mutants also displayed resistance to the antiviral T-1106, an RNA mutagen similar to ribavirin. Structural modelling of the E416K polymerase mutation indicated its location in the pinky finger domain of the RdRp, distant from the active site. Deep sequencing of the E416K mutant revealed lower genetic diversity than wild-type SLEV after growth in both vertebrate and invertebrate cells. Phenotypic characterization showed that E416K mutants displayed similar or increased replication in mammalian cells, as well as modest attenuation in mosquito cells, consistent with previous work with West Nile virus high-fidelity variants. In addition, attenuation was limited to mosquito cells with a functional RNA interference response, suggesting an impaired capacity to escape RNA interference could contribute to attenuation of high-fidelity variants. Our results provide increased evidence that RNA mutagen resistance arises through modulation of the RdRp and give further insight into the consequences of altered fidelity of flaviviruses.",,"['Griesemer, Sara B', 'Kramer, Laura D', 'Van Slyke, Greta A', 'Pata, Janice D', 'Gohara, David W', 'Cameron, Craig E', 'Ciota, Alexander T']",,,,
,PMC,The V3 Loop of HIV-1 Env Determines Viral Susceptibility to IFITM3 Impairment of Viral Infectivity,http://dx.doi.org/10.1128/JVI.02441-16,PMC5355610,,,"Interferon-inducible transmembrane proteins (IFITMs) inhibit a broad spectrum of viruses, including HIV-1. IFITM proteins deter HIV-1 entry when expressed in target cells and also impair HIV-1 infectivity when expressed in virus producer cells. However, little is known about how viruses resist IFITM inhibition. In this study, we have investigated the susceptibilities of different primary isolates of HIV-1 to the inhibition of viral infectivity by IFITMs. Our results demonstrate that the infectivity of different HIV-1 primary isolates, including transmitted founder viruses, is diminished by IFITM3 to various levels, with strain AD8-1 exhibiting strong resistance. Further mutagenesis studies revealed that HIV-1 Env, and the V3 loop sequence in particular, determines the extent of inhibition of viral infectivity by IFITM3. IFITM3-sensitive Env proteins are also more susceptible to neutralization by soluble CD4 or the 17b antibody than are IFITM3-resistant Env proteins. Together, data from our study suggest that the propensity of HIV-1 Env to sample CD4-bound-like conformations modulates viral sensitivity to IFITM3 inhibition. IMPORTANCE Results of our study have revealed the key features of the HIV-1 envelope protein that are associated with viral resistance to the IFITM3 protein. IFITM proteins are important effectors in interferon-mediated antiviral defense. A variety of viruses are inhibited by IFITMs at the virus entry step. Although it is known that envelope proteins of several different viruses resist IFITM inhibition, the detailed mechanisms are not fully understood. Taking advantage of the fact that envelope proteins of different HIV-1 strains exhibit different degrees of resistance to IFITM3 and that these HIV-1 envelope proteins share the same domain structure and similar sequences, we performed mutagenesis studies and determined the key role of the V3 loop in this viral resistance phenotype. We were also able to associate viral resistance to IFITM3 inhibition with the susceptibility of HIV-1 to inhibition by soluble CD4 and the 17b antibody that recognizes CD4-binding-induced epitopes.",,"['Wang, Yimeng', 'Pan, Qinghua', 'Ding, Shilei', 'Wang, Zhen', 'Yu, Jingyou', 'Finzi, Andrés', 'Liu, Shan-Lu', 'Liang, Chen']",,,,
,PMC,The Pseudorabies Virus Glycoprotein gE/gI Complex Suppresses Type I Interferon Production by Plasmacytoid Dendritic Cells,http://dx.doi.org/10.1128/JVI.02276-16,PMC5355608,,,"Plasmacytoid dendritic cells (pDC) play a central role in the antiviral immune response, both in the innate response and in shaping the adaptive response, mainly because of their ability to produce massive amounts of type I interferon (TI-IFN). Here, we report that cells infected with the live attenuated Bartha vaccine strain of porcine alphaherpesvirus pseudorabies virus (PRV) trigger a dramatically increased TI-IFN response by porcine primary pDC compared to cells infected with wild-type PRV strains (Becker and Kaplan). Since Bartha is one of the relatively few examples of a highly successful alphaherpesvirus vaccine, identification of factors that may contribute to its efficacy may provide insights for the rational design of other alphaherpesvirus vaccines. The Bartha vaccine genome displays several mutations compared to the genome of wild-type PRV strains, including a large deletion in the unique short (US) region, encompassing the glycoprotein E (gE), gI, US9, and US2 genes. Using recombinant PRV Becker strains harboring the entire Bartha US deletion or single mutations in the four affected US genes, we demonstrate that the absence of the viral gE/gI complex contributes to the observed increased IFN-α response. Furthermore, we show that the absence of gE leads to an enhanced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in pDC, which correlates with a higher TI-IFN production by pDC. In conclusion, the PRV Bartha vaccine strain triggers strongly increased TI-IFN production by porcine pDC. Our data further indicate that the gE/gI glycoprotein complex suppresses TI-IFN production by pDC, which represents the first alphaherpesvirus factor that suppresses pDC activity. IMPORTANCE Several alphaherpesviruses, including herpes simpex virus, still lack effective vaccines. However, the highly successful Bartha vaccine has contributed substantially to eradication of the porcine alphaherpesvirus pseudorabies virus (PRV) in several countries. The impact of Bartha on the immune response is still poorly understood. Type I interferon (TI-IFN)-producing plasmacytoid dendritic cells (pDC) may play an important role in vaccine development. Here, we show that Bartha elicits a dramatically increased type I interferon (TI-IFN) response in primary porcine pDC compared to wild-type strains. In addition, we found that the gE/gI complex, which is absent in Bartha, inhibits the pDC TI-IFN response. This is the first description of an immune cell type that is differentially affected by Bartha versus wild-type PRV and is the first report describing an alphaherpesvirus protein that inhibits the TI-IFN response by pDC. These data may therefore contribute to the rational design of other alphaherpesvirus vaccines.",,"['Lamote, Jochen A. S.', 'Kestens, Manon', 'Van Waesberghe, Cliff', 'Delva, Jonas', 'De Pelsmaeker, Steffi', 'Devriendt, Bert', 'Favoreel, Herman W.']",,,,
,PMC,"Rhinovirus C, Asthma, and Cell Surface Expression of Virus Receptor CDHR3",http://dx.doi.org/10.1128/JVI.00072-17,PMC5355607,,,"Human rhinoviruses (RVs) of the A, B, and C species are defined agents of the common cold. But more than that, RV-A and RV-C are the dominant causes of hospitalization category infections in young children, especially those with asthma. The use of cadherin-related family member 3 (CDHR3) by RV-C as its cellular receptor creates a direct phenotypic link between human genetics (G versus A alleles cause Cys529 versus Tyr529 protein variants) and the efficiency with which RV-C can infect cells. With a lower cell surface display density, the human-specific Cys529 variant apparently confers partial protection from the severest virus-induced asthma episodes. Selective pressure favoring the Cys529 codon may have coemerged with the evolution of RV-C and helped shape modern human genomes against the virus-susceptible, albeit ancestral Tyr529.",,"Palmenberg, Ann C.",,,,
,PMC,Differences in Glycoprotein Complex Receptor Binding Site Accessibility Prompt Poor Cross-Reactivity of Neutralizing Antibodies between Closely Related Arenaviruses,http://dx.doi.org/10.1128/JVI.01454-16,PMC5355595,,,"The glycoprotein complex (GPC) of arenaviruses, composed of stable signal peptide, GP1, and GP2, is the only antigen correlated with antibody-mediated neutralization. However, despite strong cross-reactivity of convalescent antisera between related arenavirus species, weak or no cross-neutralization occurs. Two closely related clade B viruses, Machupo virus (MACV) and Junín virus (JUNV), have nearly identical overall GPC architecture and share a host receptor, transferrin receptor 1 (TfR1). Given structural and functional similarities of the GP1 receptor binding site (RBS) of these viruses and the recent demonstration that the RBS is an important target for neutralizing antibodies, it is not clear how these viruses avoid cross-neutralization. To address this, MACV/JUNV chimeric GPCs were assessed for interaction with a group of α-JUNV GPC monoclonal antibodies (MAbs) and mouse antisera against JUNV or MACV GPC. All six MAbs targeted GP1, with those that neutralized JUNV GPC-pseudovirions competing with each other for RBS binding. However, these MAbs were unable to bind to a chimeric GPC composed of JUNV GP1 containing a small disulfide bonded loop (loop 10) unique to MACV GPC, suggesting that this loop may block MAbs interaction with the GP1 RBS. Consistent with this loop causing interference, mouse anti-JUNV GPC antisera that solely neutralized pseudovirions bearing autologous GP1 provided enhanced neutralization of MACV GPC when this loop was removed. Our studies provide evidence that loop 10, which is unique to MACV GP1, is an important impediment to binding of neutralizing antibodies and contributes to the poor cross-neutralization of α-JUNV antisera against MACV. IMPORTANCE Multiple New World arenaviruses can cause severe disease in humans, and some geographic overlap exists among these viruses. A vaccine that protects against a broad range of New World arenaviruses is desirable for purposes of simplicity, cost, and broad protection against multiple National Institute of Allergy and Infectious Disease-assigned category A priority pathogens. In this study, we sought to better understand how closely related arenaviruses elude cross-species neutralization by investigating the structural bases of antibody binding and avoidance. In our studies, we found that neutralizing antibodies against two New World arenaviruses, Machupo virus (MACV) and Junín virus (JUNV), bound to the envelope glycoprotein 1 (GP1) with JUNV monoclonal antibodies targeting the receptor binding site (RBS). We further show that altered structures surrounding the RBS pocket in MACV GP1 impede access of JUNV-elicited antibodies.",,"['Brouillette, Rachel B.', 'Phillips, Elisabeth K.', 'Ayithan, Natarajan', 'Maury, Wendy']",,,,
,PMC,Expression of Ifnlr1 on Intestinal Epithelial Cells Is Critical to the Antiviral Effects of Interferon Lambda against Norovirus and Reovirus,http://dx.doi.org/10.1128/JVI.02079-16,PMC5355594,,,"Lambda interferon (IFN-λ) has potent antiviral effects against multiple enteric viral pathogens, including norovirus and rotavirus, in both preventing and curing infection. Because the intestine includes a diverse array of cell types, however, the cell(s) upon which IFN-λ acts to exert its antiviral effects is unclear. Here, we sought to identify IFN-λ-responsive cells by generation of mice with lineage-specific deletion of the receptor for IFN-λ, Ifnlr1. We found that expression of IFNLR1 on intestinal epithelial cells (IECs) in the small intestine and colon is required for enteric IFN-λ antiviral activity. IEC Ifnlr1 expression also determines the efficacy of IFN-λ in resolving persistent murine norovirus (MNoV) infection and regulates fecal shedding and viral titers in tissue. Thus, the expression of Ifnlr1 by IECs is necessary for the response to both endogenous and exogenous IFN-λ. We further demonstrate that IEC Ifnlr1 expression is required for the sterilizing innate immune effects of IFN-λ by extending these findings in Rag1-deficient mice. Finally, we assessed whether our findings pertained to multiple viral pathogens by infecting mice specifically lacking IEC Ifnlr1 expression with reovirus. These mice phenocopied Ifnlr1-null animals, exhibiting increased intestinal tissue titers and enhanced reovirus fecal shedding. Thus, IECs are the critical cell type responding to IFN-λ to control multiple enteric viruses. This is the first genetic evidence that supports an essential role for IECs in IFN-λ-mediated control of enteric viral infection, and these findings provide insight into the mechanism of IFN-λ-mediated antiviral activity. IMPORTANCE Human noroviruses (HNoVs) are the leading cause of epidemic gastroenteritis worldwide. Type III interferons (IFN-λ) control enteric viral infections in the gut and have been shown to cure mouse norovirus, a small-animal model for HNoVs. Using a genetic approach with conditional knockout mice, we identified IECs as the dominant IFN-λ-responsive cells in control of enteric virus infection in vivo. Upon murine norovirus or reovirus infection, Ifnlr1 depletion in IECs largely recapitulated the phenotype seen in Ifnlr1(−/−) mice of higher intestinal tissue viral titers and increased viral shedding in the stool. Moreover, IFN-λ-mediated sterilizing immunity against murine norovirus requires the capacity of IECs to respond to IFN-λ. These findings clarify the mechanism of action of this cytokine and emphasize the therapeutic potential of IFN-λ for treating mucosal viral infections.",,"['Baldridge, Megan T.', 'Lee, Sanghyun', 'Brown, Judy J.', 'McAllister, Nicole', 'Urbanek, Kelly', 'Dermody, Terence S.', 'Nice, Timothy J.', 'Virgin, Herbert W.']",,,,
,PMC,"Contact structure, mobility, environmental impact and behaviour: the importance of social forces to infectious disease dynamics and disease ecology",http://dx.doi.org/10.1098/rstb.2016.0454,PMC5352824,,,"Human factors, including contact structure, movement, impact on the environment and patterns of behaviour, can have significant influence on the emergence of novel infectious diseases and the transmission and amplification of established ones. As anthropogenic climate change alters natural systems and global economic forces drive land-use and land-cover change, it becomes increasingly important to understand both the ecological and social factors that impact infectious disease outcomes for human populations. While the field of disease ecology explicitly studies the ecological aspects of infectious disease transmission, the effects of the social context on zoonotic pathogen spillover and subsequent human-to-human transmission are comparatively neglected in the literature. The social sciences encompass a variety of disciplines and frameworks for understanding infectious diseases; however, here we focus on four primary areas of social systems that quantitatively and qualitatively contribute to infectious diseases as social–ecological systems. These areas are social mixing and structure, space and mobility, geography and environmental impact, and behaviour and behaviour change. Incorporation of these social factors requires empirical studies for parametrization, phenomena characterization and integrated theoretical modelling of social–ecological interactions. The social–ecological system that dictates infectious disease dynamics is a complex system rich in interacting variables with dynamically significant heterogeneous properties. Future discussions about infectious disease spillover and transmission in human populations need to address the social context that affects particular disease systems by identifying and measuring qualitatively important drivers. This article is part of the themed issue ‘Opening the black box: re-examining the ecology and evolution of parasite transmission’.",,"['Arthur, Ronan F.', 'Gurley, Emily S.', 'Salje, Henrik', 'Bloomfield, Laura S. P.', 'Jones, James H.']",,,,
,PMC,Receptor-binding domain of MERS-CoV with optimal immunogen dosage and immunization interval protects human transgenic mice from MERS-CoV infection,http://dx.doi.org/10.1080/21645515.2017.1296994,PMC5512770,,,"Middle East respiratory syndrome (MERS) continues to raise worldwide concerns due to its pandemic potential. Increased MERS cases and no licensed MERS vaccines highlight the need to develop safe and effective vaccines against MERS. We have previously demonstrated that a receptor-binding domain (RBD) fragment containing residues 377–588 of MERS-coronavirus (MERS-CoV) spike protein is a critical neutralizing domain and an important vaccine target. Nevertheless, its optimal immunogen dosage and immunization interval, key factors for human-used vaccines that induce protective immunity, have never been investigated. In this study, we optimized these criteria using a recombinant MERS-CoV RBD protein fused with Fc (S377–588-Fc) and utilized the optimal immunization schedule to evaluate the protective efficacy of RBD against MERS-CoV infection in human dipeptidyl peptidase 4 transgenic (hDPP4-Tg) mice. Compared with one dose and 2 doses at 1-, 2-, and 3-week intervals, a regimen of 2 doses of this protein separated by an interval of 4 weeks induced the strongest antibody response and neutralizing antibodies against MERS-CoV infection, and maintained at a high level during the detection period. Notably, RBD protein at the optimal dosage and interval protected hDPP4-Tg mice against lethal MERS-CoV challenge, and the protection was positively correlated with serum neutralizing antibodies. Taken together, the optimal immunogen dosage and immunization interval identified in this study will provide useful guidelines for further development of MERS-CoV RBD-based vaccines for human use.",,"['Wang, Yufei', 'Tai, Wanbo', 'Yang, Jie', 'Zhao, Guangyu', 'Sun, Shihui', 'Tseng, Chien-Te K.', 'Jiang, Shibo', 'Zhou, Yusen', 'Du, Lanying', 'Gao, Jimin']",,,,
,PMC,Viral interference and the live-attenuated intranasal influenza vaccine: Results from a pediatric cohort with cystic fibrosis,http://dx.doi.org/10.1080/21645515.2017.1287641,PMC5489283,,,"Background: The objective of this study was to explore the effects of viral co-detection in individuals recently vaccinated with the live-attenuated intranasal influenza virus vaccine (LAIV) on the detection of influenza RNA. Methods: Before the 2013–2014 influenza season, nasal swabs were obtained from 59 pediatric participants with cystic fibrosis (CF) and 17 of their healthy siblings immediately before vaccination and 4 times during the week of follow-up. Real-time RT-PCR assays were used to detect influenza RNA. Co-detection of a non-influenza respiratory virus (NIRV) at the time of vaccination was determined by a multiplex RT-PCR assay. Differences in the proportions and rates of influenza detection and their 95% credible intervals (CrI) were estimated. Results: Influenza RNA was detected in 16% fewer participants (95% CrI: −7, 39%) throughout follow-up in the NIRV-positive group compared with the NIRV-negative group (59% vs. 75%). This was also observed in participants with CF alone (66% vs. 74%; RD = 8% 95% CrI: −16, 33%) as well as in healthy participants only (75% vs. 30%; RD = 45%, 95% CrI: −2, 81%). Influenza was detected in NIRV-negative subjects for 0.49 d more compared with NIRV-positive subjects (95% CrI: −0.37, 1.26). Conclusion: The observed proportion of subjects in whom influenza RNA was detected and the duration of detection differed slightly between NIRV- positive and −negative subjects. However, wide credible intervals for the difference preclude definitive conclusions. If true, this observed association may be related to a recent viral respiratory infection, a phenomenon known as viral interference.",,"['Boikos, Constantina', 'Papenburg, Jesse', 'Martineau, Christine', 'Joseph, Lawrence', 'Scheifele, David', 'Chilvers, Mark', 'Lands, Larry C.', 'De Serres, Gaston', 'Quach, Caroline']",,,,
,PMC,Notes on Contributors,http://dx.doi.org/10.1111/1468-0009.12250,PMC5339377,,,,,,,,,
,PMC,Multiple origins of viral capsid proteins from cellular ancestors,http://dx.doi.org/10.1073/pnas.1621061114,PMC5373398,,,"Viruses are the most abundant biological entities on earth and show remarkable diversity of genome sequences, replication and expression strategies, and virion structures. Evolutionary genomics of viruses revealed many unexpected connections but the general scenario(s) for the evolution of the virosphere remains a matter of intense debate among proponents of the cellular regression, escaped genes, and primordial virus world hypotheses. A comprehensive sequence and structure analysis of major virion proteins indicates that they evolved on about 20 independent occasions, and in some of these cases likely ancestors are identifiable among the proteins of cellular organisms. Virus genomes typically consist of distinct structural and replication modules that recombine frequently and can have different evolutionary trajectories. The present analysis suggests that, although the replication modules of at least some classes of viruses might descend from primordial selfish genetic elements, bona fide viruses evolved on multiple, independent occasions throughout the course of evolution by the recruitment of diverse host proteins that became major virion components.",,"['Krupovic, Mart', 'Koonin, Eugene V.']",,,,
,PMC,The Maternal Plasma Proteome Changes as a Function of Gestational Age in Normal Pregnancy: a Longitudinal Study,http://dx.doi.org/10.1016/j.ajog.2017.02.037,PMC5813489,,,"OBJECTIVE: Pregnancy is accompanied by dramatic physiologic changes in maternal plasma proteins. Characterization of the maternal plasma proteome in normal pregnancy is an essential step for understanding changes to predict pregnancy outcome. The objective of this study was to describe maternal plasma proteins that change in abundance with advancing gestational age, and determine biological processes that are perturbed in normal pregnancy. MATERIALS AND METHODS: A longitudinal study included 43 normal pregnancies that had a term delivery of an infant who was appropriate for gestational age (AGA) without maternal or neonatal complications. For each pregnancy, 3 to 6 maternal plasma samples (median=5,) were profiled to measure the abundance of 1,125 proteins using multiplex assays. Linear mixed effects models with polynomial splines were used to model protein abundance as a function of gestational age, and significance of the association was inferred via likelihood ratio tests. Proteins considered to be significantly changed were defined as having: 1) more than 1.5 fold change between 8 and 40 weeks of gestation; and 2) a false discovery rate (FDR) adjusted p-value <0.1. Gene ontology enrichment analysis was employed to identify biological processes over-represented among the proteins that changed with advancing gestation. RESULTS: 1) Ten percent (112/1,125) of the profiled proteins changed in abundance as a function of gestational age; 2) of the 1,125 proteins analyzed Glypican-3, sialic acid-binding immunoglobulin-type lectins (Siglec)-6, placental growth factor (PlGF), C-C motif (CCL)-28, carbonic anhydrase 6, Prolactin (PRL), interleukin-1 receptor 4 (IL-1 R4), dual specificity mitogen-activated protein kinase 4 (MP2K4) and pregnancy-associated plasma protein-A (PAPP-A) had more than 5 fold change in abundance across gestation. These 9 proteins are known to be involved in a wide range of both physiologic and pathologic processes, such as growth regulation, embryogenesis, angiogenesis immunoregulation, inflammation etc.; and 3) biological processes associated with protein changes in normal pregnancy included defense response, defense response to bacteria, proteolysis and leukocyte migration (FDR=10%). CONCLUSIONS: The plasma proteome of normal pregnancy demonstrates dramatic changes in both magnitude of changes and the fraction of the proteins involved. Such information is important to understand the physiology of pregnancy, development of biomarkers to differentiate normal vs. abnormal pregnancy, and determine the response to interventions.",,"['Romero, Roberto', 'Erez, Offer', 'Maymon, Eli', 'Chaemsaithong, Piya', 'Xu, Zhonghui', 'Pacora, Percy', 'Chaiworapongsa, Tinnakorn', 'Done, Bogdan', 'Hassan, Sonia S.', 'Tarca, Adi L.']",,,,
,PMC,Global Analysis of SUMO-Binding Proteins Identifies SUMOylation as a Key Regulator of the INO80 Chromatin Remodeling Complex,http://dx.doi.org/10.1074/mcp.M116.063719,PMC5417823,,,"SUMOylation is a critical regulator of a broad range of cellular processes, and is thought to do so in part by modulation of protein interaction. To comprehensively identify human proteins whose interaction is modulated by SUMOylation, we developed an in vitro binding assay using human proteome microarrays to identify targets of SUMO1 and SUMO2. We then integrated these results with protein SUMOylation and protein-protein interaction data to perform network motif analysis. We focused on a single network motif we termed a SUMOmodPPI (SUMO-modulated Protein-Protein Interaction) that included the INO80 chromatin remodeling complex subunits TFPT and INO80E. We validated the SUMO-binding activity of INO80E, and showed that TFPT is a SUMO substrate both in vitro and in vivo. We then demonstrated a key role for SUMOylation in mediating the interaction between these two proteins, both in vitro and in vivo. By demonstrating a key role for SUMOylation in regulating the INO80 chromatin remodeling complex, this work illustrates the power of bioinformatics analysis of large data sets in predicting novel biological phenomena.",,"['Cox, Eric', 'Hwang, Woochang', 'Uzoma, Ijeoma', 'Hu, Jianfei', 'Guzzo, Catherine M.', 'Jeong, Junseop', 'Matunis, Michael J.', 'Qian, Jiang', 'Zhu, Heng', 'Blackshaw, Seth']",,,,
,PMC,Lung ischemia reperfusion injury: the therapeutic role of dipeptidyl peptidase 4 inhibition,http://dx.doi.org/10.21037/atm.2017.01.41,PMC5395493,,,"Dipeptidyl peptidase 4 (DPP4) is a cell surface protease that has been reported to play a role in glucose homeostasis, cancer, HIV, autoimmunity, immunology and inflammation. A role for DPP4 in ischemia-reperfusion injury (IRI) in the heart has been established. Dipeptidyl peptidase 4 inhibition (DPP4i) appeared to decrease infarct size, improves cardiac function and promotes myocardial regeneration. Lung ischemia reperfusion injury is caused by a complex mechanism in which macrophages and neutrophils play an important role. Generation of reactive oxygen species (ROS), uncoupling of nitric oxide synthase (NOS), activation of nuclear factor-κB (NF-κB), activation of nicotinamide adenine dinucleotide phosphate metabolism, and generation of pro-inflammatory cytokines lead to acute lung injury (ALI). In this review we present the current knowledge on DPP4 as a target to treat IRI in the lung. We also provide evidence of the roles of the DPP4 substrates glucagon-like peptide 1 (GLP-1), vasoactive intestinal peptide (VIP) and stromal cell-derived factor-1α (SDF-1α) in protection against oxidative stress through activation of the mitogen-activated protein kinase (MAPK) 1/2 and phosphatidylinositol 3'-kinase (PI3K)/Akt signal transduction pathways.",,"['Beckers, Paul A. J.', 'Gielis, Jan F.', 'Van Schil, Paul E.', 'Adriaensen, Dirk']",,,,
,PMC,The expression of proline-specific enzymes in the human lung,http://dx.doi.org/10.21037/atm.2017.03.36,PMC5395489,,,"The pathophysiology of lung diseases is very complex and proteolytic enzymes may play a role or could be used as biomarkers. In this review, the literature was searched to make an overview of what is known on the expression of the proline-specific peptidases dipeptidyl peptidase (DPP) 4, 8, 9, prolyl oligopeptidase (PREP) and fibroblast activation protein α (FAP) in the healthy and diseased lung. Search terms included asthma, chronic obstructive pulmonary disease (COPD), lung cancer, fibrosis, ischemia reperfusion injury and pneumonia. Knowledge on the loss or gain of protein expression and activity during disease might tie these enzymes to certain cell types, substrates or interaction partners that are involved in the pathophysiology of the disease, ultimately leading to the elucidation of their functional roles and a potential therapeutic target. Most data could be found on DPP4, while the other enzymes are less explored. Published data however often appear to be conflicting, the applied methods divers and the specificity of the assays used questionable. In conclusion, information on the expression of the proline-specific peptidases in the healthy and diseased lung is lacking, begging for further well-designed research.",,"['Vliegen, Gwendolyn', 'Raju, Tom K.', 'Adriaensen, Dirk', 'Lambeir, Anne-Marie', 'De Meester, Ingrid']",,,,
,PMC,Hypusination of eIF5A as a Target for Antiviral Therapy,http://dx.doi.org/10.1089/dna.2016.3611,PMC5346904,,,,,"['Olsen, Michelle E.', 'Connor, John H.']",,,,
,PMC,CEPI – A global partnership,http://dx.doi.org/10.18683/germs.2017.1102,PMC5348218,,,,,"Roberts, Richard B",,,,
,PMC,Searching for a Lifeline: Transcriptome Profiling Studies of Influenza Susceptibility and Resistance,http://dx.doi.org/10.1159/000457902,PMC6738832,,,"Excess or dysregulated host inflammatory responses cause much of the morbidity and mortality caused by severe influenza. Given the limitations of vaccines and antiviral drugs, novel therapeutics to modulate host responses and improve outcomes in severe influenza are needed. One strategy is to learn from the direct comparison of high-survivor versus high-mortality animal models. This review surveys the results of lung transcriptome profiling studies in murine models that directly compare susceptible versus resistant hosts challenged with identical influenza infections. The potential contributions and limitations of these studies are discussed. To amplify their power, the studies are subjected to a meta-analysis, which helps identify frequently dysregulated pathways and potentially novel areas for investigation. Using connectivity map-based tools (LINCS), transcriptome signatures linked to susceptibility can identify candidate drugs that merit testing for in vivo efficacy.",,"Kobzik, Lester",,,,
,PMC,Post-translational modification directs nuclear and hyphal tip localization of C. albicans mRNA-binding protein Slr1,http://dx.doi.org/10.1111/mmi.13643,PMC5405739,,,"The morphological transition of the opportunistic fungal pathogen Candida albicans from budding to hyphal growth has been implicated in its ability to cause disease in animal models. Absence of SR-like RNA-binding protein Slr1 slows hyphal formation and decreases virulence in a systemic candidiasis model, suggesting a role for post-transcriptional regulation in these processes. SR (serine-arginine)-rich proteins influence multiple steps in mRNA metabolism and their localization and function are frequently controlled by modification. We now demonstrate that Slr1 binds to polyadenylated RNA and that its intracellular localization is modulated by phosphorylation and methylation. Wildtype Slr1-GFP is predominantly nuclear, but also co-fractionates with translating ribosomes. The non-phosphorylatable slr1-6SA-GFP protein, in which six serines in SR/RS clusters are substituted with alanines, primarily localizes to the cytoplasm in budding cells. Intriguingly, hyphal cells display an slr1-6SA-GFP focus at the tip near the Spitzenkörper, a vesicular structure involved in molecular trafficking to the tip. The presence of slr1-6SA-GFP hyphal tip foci is reduced in the absence of the mRNA-transport protein She3, suggesting that unphosphorylated Slr1 associates with mRNA-protein complexes transported to the tip. The impact of SLR1 deletion on hyphal formation and function thus may be partially due to a role in hyphal mRNA transport.",,"['Ariyachet, Chaiyaboot', 'Beißel, Christian', 'Li, Xiang', 'Lorrey, Selena', 'Mackenzie, Olivia', 'Martin, Patrick M.', 'O’Brien, Katharine', 'Pholcharee, Tossapol', 'Sim, Sue', 'Krebber, Heike', 'McBride, Anne E.']",,,,
,PMC,Structure of human IFIT1 with capped RNA reveals adaptable mRNA binding and mechanisms for sensing N1 and N2 ribose 2′-O methylations,http://dx.doi.org/10.1073/pnas.1612444114,PMC5358387,,,"IFIT1 (IFN-induced protein with tetratricopeptide repeats-1) is an effector of the host innate immune antiviral response that prevents propagation of virus infection by selectively inhibiting translation of viral mRNA. It relies on its ability to compete with the translation initiation factor eIF4F to specifically recognize foreign capped mRNAs, while remaining inactive against host mRNAs marked by ribose 2′-O methylation at the first cap-proximal nucleotide (N1). We report here several crystal structures of RNA-bound human IFIT1, including a 1.6-Å complex with capped RNA. IFIT1 forms a water-filled, positively charged RNA-binding tunnel with a separate hydrophobic extension that unexpectedly engages the cap in multiple conformations (syn and anti) giving rise to a relatively plastic and nonspecific mode of binding, in stark contrast to eIF4E. Cap-proximal nucleotides encircled by the tunnel provide affinity to compete with eIF4F while allowing IFIT1 to select against N1 methylated mRNA. Gel-shift binding assays confirm that N1 methylation interferes with IFIT1 binding, but in an RNA-dependent manner, whereas translation assays reveal that N1 methylation alone is not sufficient to prevent mRNA recognition at high IFIT1 concentrations. Structural and functional analysis show that 2′-O methylation at N2, another abundant mRNA modification, is also detrimental for RNA binding, thus revealing a potentially synergistic role for it in self- versus nonself-mRNA discernment. Finally, structure-guided mutational analysis confirms the importance of RNA binding for IFIT1 restriction of a human coronavirus mutant lacking viral N1 methylation. Our structural and biochemical analysis sheds new light on the molecular basis for IFIT1 translational inhibition of capped viral RNA.",,"['Abbas, Yazan M.', 'Laudenbach, Beatrice Theres', 'Martínez-Montero, Saúl', 'Cencic, Regina', 'Habjan, Matthias', 'Pichlmair, Andreas', 'Damha, Masad J.', 'Pelletier, Jerry', 'Nagar, Bhushan']",,,,
,PMC,The uncoupling of catalysis and translocation in the viral RNA-dependent RNA polymerase,http://dx.doi.org/10.1080/15476286.2017.1300221,PMC5711473,,,"The nucleotide addition cycle of nucleic acid polymerases includes 2 major events: the pre-chemistry active site closure leading to the addition of one nucleotide to the product chain; the post-chemistry translocation step moving the polymerase active site one position downstream on its template. In viral RNA-dependent RNA polymerases (RdRPs), structural and biochemical evidences suggest that these 2 events are not tightly coupled, unlike the situation observed in A-family polymerases such as the bacteriophage T7 RNA polymerase. Recently, an RdRP translocation intermediate crystal structure of enterovirus 71 shed light on how translocation may be controlled by elements within RdRP catalytic motifs, and a series of poliovirus apo RdRP crystal structures explicitly suggest that a motif B loop may assist the movement of the template strand in late stages of transcription. Implications of RdRP catalysis-translocation uncoupling and the remaining challenges to further elucidate RdRP translocation mechanism are also discussed.",,"['Shu, Bo', 'Gong, Peng']",,,,
,PMC,Expanded polyalanine tracts function as nuclear export signals and promote protein mislocalization via eEF1A1 factor,http://dx.doi.org/10.1074/jbc.M116.763599,PMC5392573,,,"Polyalanine (poly(A)) diseases are caused by the expansion of translated GCN triplet nucleotide sequences encoding poly(A) tracts in proteins. To date, nine human disorders have been found to be associated with poly(A) tract expansions, including congenital central hypoventilation syndrome and oculopharyngeal muscular dystrophy. Previous studies have demonstrated that unexpanded wild-type poly(A)-containing proteins localize to the cell nucleus, whereas expanded poly(A)-containing proteins primarily localize to the cytoplasm. Because most of these poly(A) disease proteins are transcription factors, this mislocalization causes cellular transcriptional dysregulation leading to cellular dysfunction. Correcting this faulty localization could potentially point to strategies to treat the aforementioned disorders, so there is a pressing need to identify the mechanisms underlying the mislocalization of expanded poly(A) protein. Here, we performed a glutathione S-transferase pulldown assay followed by mass spectrometry and identified eukaryotic translation elongation factor 1 α1 (eEF1A1) as an interacting partner with expanded poly(A)-containing proteins. Strikingly, knockdown of eEF1A1 expression partially corrected the mislocalization of the expanded poly(A) proteins in the cytoplasm and restored their functions in the nucleus. We further demonstrated that the expanded poly(A) domain itself can serve as a nuclear export signal. Taken together, this study demonstrates that eEF1A1 regulates the subcellular location of expanded poly(A) proteins and is therefore a potential therapeutic target for combating the pathogenesis of poly(A) diseases.",,"['Li, Li', 'Ng, Nelson Ka Lam', 'Koon, Alex Chun', 'Chan, Ho Yin Edwin']",,,,
,PMC,"Domain Organization and Evolution of the Highly Divergent 5′ Coding Region of Genomes of Arteriviruses, Including the Novel Possum Nidovirus",http://dx.doi.org/10.1128/JVI.02096-16,PMC5331827,,,"In five experimentally characterized arterivirus species, the 5′-end genome coding region encodes the most divergent nonstructural proteins (nsp's), nsp1 and nsp2, which include papain-like proteases (PLPs) and other poorly characterized domains. These are involved in regulation of transcription, polyprotein processing, and virus-host interaction. Here we present results of a bioinformatics analysis of this region of 14 arterivirus species, including that of the most distantly related virus, wobbly possum disease virus (WPDV), determined by a modified 5′ rapid amplification of cDNA ends (RACE) protocol. By combining profile-profile comparisons and phylogeny reconstruction, we identified an association of the four distinct domain layouts of nsp1-nsp2 with major phylogenetic lineages, implicating domain gain, including duplication, and loss in the early nsp1 evolution. Specifically, WPDV encodes highly divergent homologs of PLP1a, PLP1b, PLP1c, and PLP2, with PLP1a lacking the catalytic Cys residue, but does not encode nsp1 Zn finger (ZnF) and “nuclease” domains, which are conserved in other arteriviruses. Unexpectedly, our analysis revealed that the only catalytically active nsp1 PLP of equine arteritis virus (EAV), known as PLP1b, is most similar to PLP1c and thus is likely to be a PLP1b paralog. In all non-WPDV arteriviruses, PLP1b/c and PLP1a show contrasting patterns of conservation, with the N- and C-terminal subdomains, respectively, being enriched with conserved residues, which is indicative of different functional specializations. The least conserved domain of nsp2, the hypervariable region (HVR), has its size varied 5-fold and includes up to four copies of a novel PxPxPR motif that is potentially recognized by SH3 domain-containing proteins. Apparently, only EAV lacks the signal that directs −2 ribosomal frameshifting in the nsp2 coding region. IMPORTANCE Arteriviruses comprise a family of mammalian enveloped positive-strand RNA viruses that include some of the most economically important pathogens of swine. Most of our knowledge about this family has been obtained through characterization of viruses from five species: Equine arteritis virus, Simian hemorrhagic fever virus, Lactate dehydrogenase-elevating virus, Porcine respiratory and reproductive syndrome virus 1, and Porcine respiratory and reproductive syndrome virus 2. Here we present the results of comparative genomics analyses of viruses from all known 14 arterivirus species, including the most distantly related virus, WPDV, whose genome sequence was completed in this study. Our analysis focused on the multifunctional 5′-end genome coding region that encodes multidomain nonstructural proteins 1 and 2. Using diverse bioinformatics techniques, we identified many patterns of evolutionary conservation that are specific to members of distinct arterivirus species, both characterized and novel, or their groups. They are likely associated with structural and functional determinants important for virus replication and virus-host interaction.",,"['Gulyaeva, Anastasia', 'Dunowska, Magdalena', 'Hoogendoorn, Erik', 'Giles, Julia', 'Samborskiy, Dmitry', 'Gorbalenya, Alexander E.']",,,,
,PMC,Viral RNA at Two Stages of Reovirus Infection Is Required for the Induction of Necroptosis,http://dx.doi.org/10.1128/JVI.02404-16,PMC5331789,,,"Necroptosis, a regulated form of necrotic cell death, requires the activation of the RIP3 kinase. Here, we identify that infection of host cells with reovirus can result in necroptosis. We find that necroptosis requires sensing of the genomic RNA within incoming virus particles via cytoplasmic RNA sensors to produce type I interferon (IFN). While these events that occur prior to the de novo synthesis of viral RNA are required for the induction of necroptosis, they are not sufficient. The induction of necroptosis also requires late stages of reovirus infection. Specifically, efficient synthesis of double-stranded RNA (dsRNA) within infected cells is required for necroptosis. These data indicate that viral RNA interfaces with host components at two different stages of infection to induce necroptosis. This work provides new molecular details about events in the viral replication cycle that contribute to the induction of necroptosis following infection with an RNA virus. IMPORTANCE An appreciation of how cell death pathways are regulated following viral infection may reveal strategies to limit tissue destruction and prevent the onset of disease. Cell death following virus infection can occur by apoptosis or a regulated form of necrosis known as necroptosis. Apoptotic cells are typically disposed of without activating the immune system. In contrast, necroptotic cells alert the immune system, resulting in inflammation and tissue damage. While apoptosis following virus infection has been extensively investigated, how necroptosis is unleashed following virus infection is understood for only a small group of viruses. Here, using mammalian reovirus, we highlight the molecular mechanism by which infection with a dsRNA virus results in necroptosis.",,"['Berger, Angela K.', 'Hiller, Bradley E.', 'Thete, Deepti', 'Snyder, Anthony J.', 'Perez, Encarnacion', 'Upton, Jason W.', 'Danthi, Pranav']",,,,
,PMC,Beyond attachment: roles of DC-SIGN in dengue virus infection,http://dx.doi.org/10.1111/tra.12469,PMC5526227,,,"DC-SIGN, a C-type lectin expressed on the plasma membrane by human immature dendritic cells, is a receptor for numerous viruses including Ebola, SARS, and dengue. A controversial question has been whether DC-SIGN functions as a complete receptor for both binding and internalization of dengue virus (DENV) or whether it is solely a cell surface attachment factor, requiring either hand-off to another receptor or a co-receptor for internalization. To examine this question, we used four cell types: human immature dendritic cells and NIH3T3 cells expressing either wild type DC-SIGN or two internalization-deficient DC-SIGN mutants, in which either the three cytoplasmic internalization motifs are silenced by alanine substitutions or the cytoplasmic region is truncated. Using confocal and super-resolution imaging and high content single particle tracking, we investigated DENV binding, DC-SIGN surface transport, endocytosis, as well as cell infectivity. DC-SIGN was found colocalized with DENV inside cells suggesting hand-off at the plasma membrane to another receptor did not occur. Moreover, all three DC-SIGN molecules on NIH3T3 cells supported cell infection. These results imply the involvement of a co-receptor because cells expressing the internalization-deficient mutants could still be infected.",,"['Liu, Ping', 'Ridilla, Marc', 'Patel, Pratik', 'Betts, Laurie', 'Gallichotte, Emily', 'Shahidi, Lidea', 'Thompson, Nancy L.', 'Jacobson, Ken']",,,,
,PMC,Exchange proteins directly activated by cAMP (EPACs): Emerging therapeutic targets,http://dx.doi.org/10.1016/j.bmcl.2017.02.065,PMC5397994,,,"Exchange proteins directly activated by cAMP (EPACs) are critical cAMP-dependent signaling pathway mediators. The discovery of EPAC proteins has significantly facilitated understanding on cAMP-dependent signaling pathway and efforts along this line open new avenues for developing novel therapeutics for cancer, diabetes, heart failure, inflammation, infections, neurological disorders and other human diseases. Over the past decade, important progress has been made in the identification of EPAC agonists, antagonists and their biological and pharmacological applications. In this review, we briefly summarize recently reported novel functions of EPACs and the discovery of their small molecule modulators. The challenges and future perspectives are also discussed.",,"['Wang, Pingyuan', 'Liu, Zhiqing', 'Chen, Haiying', 'Ye, Na', 'Cheng, Xiaodong', 'Zhou, Jia']",,,,
,PMC,Obatoclax Inhibits Alphavirus Membrane Fusion by Neutralizing the Acidic Environment of Endocytic Compartments,http://dx.doi.org/10.1128/AAC.02227-16,PMC5328557,,,"As new pathogenic viruses continue to emerge, it is paramount to have intervention strategies that target a common denominator in these pathogens. The fusion of viral and cellular membranes during viral entry is one such process that is used by many pathogenic viruses, including chikungunya virus, West Nile virus, and influenza virus. Obatoclax, a small-molecule antagonist of the Bcl-2 family of proteins, was previously determined to have activity against influenza A virus and also Sindbis virus. Here, we report it to be active against alphaviruses, like chikungunya virus (50% effective concentration [EC(50)] = 0.03 μM) and Semliki Forest virus (SFV; EC(50) = 0.11 μM). Obatoclax inhibited viral entry processes in an SFV temperature-sensitive mutant entry assay. A neutral red retention assay revealed that obatoclax induces the rapid neutralization of the acidic environment of endolysosomal vesicles and thereby most likely inhibits viral fusion. Characterization of escape mutants revealed that the L369I mutation in the SFV E1 fusion protein was sufficient to confer partial resistance against obatoclax. Other inhibitors that target the Bcl-2 family of antiapoptotic proteins inhibited neither viral entry nor endolysosomal acidification, suggesting that the antiviral mechanism of obatoclax does not depend on its anticancer targets. Obatoclax inhibited the growth of flaviviruses, like Zika virus, West Nile virus, and yellow fever virus, which require low pH for fusion, but not that of pH-independent picornaviruses, like coxsackievirus A9, echovirus 6, and echovirus 7. In conclusion, obatoclax is a novel inhibitor of endosomal acidification that prevents viral fusion and that could be pursued as a potential broad-spectrum antiviral candidate.",,"['Varghese, Finny S.', 'Rausalu, Kai', 'Hakanen, Marika', 'Saul, Sirle', 'Kümmerer, Beate M.', 'Susi, Petri', 'Merits, Andres', 'Ahola, Tero']",,,,
,PMC,MERS-CoV spike nanoparticles protect mice from MERS-CoV infection,http://dx.doi.org/10.1016/j.vaccine.2017.02.012,PMC5423355,,,"The Middle East respiratory syndrome coronavirus (MERS-CoV) was first discovered in late 2012 and has gone on to cause over 1800 infections and 650 deaths. There are currently no approved therapeutics or vaccinations for MERS-CoV. The MERS-CoV spike (S) protein is responsible for receptor binding and virion entry to cells, is immunodominant and induces neutralizing antibodies in vivo, all of which, make the S protein an ideal target for anti-MERS-CoV vaccines. In this study, we demonstrate protection induced by vaccination with a recombinant MERS-CoV S nanoparticle vaccine and Matrix-M1 adjuvant combination in mice. The MERS-CoV S nanoparticle vaccine produced high titer anti-S neutralizing antibody and protected mice from MERS-CoV infection in vivo.",,"['Coleman, Christopher M.', 'Venkataraman, Thiagarajan', 'Liu, Ye V.', 'Glenn, Gregory M.', 'Smith, Gale E.', 'Flyer, David C.', 'Frieman, Matthew B.']",,,,
,PMC,Ebola Preparedness: Diagnosis Improvement Using Rapid Approaches for Proficiency Testing,http://dx.doi.org/10.1128/JCM.02173-16,PMC5328446,,,"The unprecedented 2015 Ebolavirus (EBOV) outbreak in West Africa was declared a public health emergency, making diagnosis and quality of testing a global issue. The accuracy of laboratory diagnostic capacity for EBOV was assessed in 2014 to 2016 using a proficiency testing (PT) strategy developed by the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) in Biosecurity. Following a literature search, EBOV-specific gene targets were ranked according to the frequency of their use in published methods. The most commonly used gene regions (nucleoprotein [NP], glycoprotein [GP], and RNA-dependent RNA polymerase [L]) were selected for the design of in vitro RNA transcripts to be included in the simulated EBOV specimens used for EBOV detection with PCR-based assays. Specimens were tested for stability and found to be stable on long-term storage (1 year) at −80°C and on shorter-term storage in lyophilized form (1 week at ambient temperature and a subsequent week at −80°C). These specimens were used in three EBOV PTs offered from April 2014 to March 2016. In the first and third PTs, all laboratories (3/3 and 9/9, respectively) correctly identified specimens containing EBOV RNA transcripts, while in the second PT, all but one laboratory (5/6) correctly confirmed the presence of EBOV. The EBOV PT panel was useful for ensuring the competency of laboratories in detecting EBOV in the absence of readily available clinical samples. The simulated EBOV specimen was safe, stable, and reliable and can be used in lyophilized form for future EBOV PT programs, allowing simplicity of transport.",,"['Lau, Katherine A.', 'Theis, Torsten', 'Gray, Joanna', 'Rawlinson, William D.']",,,,
,PMC,Integrating Advanced Molecular Technologies into Public Health,http://dx.doi.org/10.1128/JCM.01967-16,PMC5328438,,,"Advances in laboratory and information technologies are transforming public health microbiology. High-throughput genome sequencing and bioinformatics are enhancing our ability to investigate and control outbreaks, detect emerging infectious diseases, develop vaccines, and combat antimicrobial resistance, all with increased accuracy, timeliness, and efficiency. The Advanced Molecular Detection (AMD) initiative has allowed the Centers for Disease Control and Prevention (CDC) to provide leadership and coordination in integrating new technologies into routine practice throughout the U.S. public health laboratory system. Collaboration and partnerships are the key to navigating this transition and to leveraging the next generation of methods and tools most effectively for public health.",,"['Gwinn, Marta', 'MacCannell, Duncan R.', 'Khabbaz, Rima F.']",,,,
,PMC,Vitrification after multiple rounds of sample application and blotting improves particle density on cryo-electron microscopy grids,http://dx.doi.org/10.1016/j.jsb.2017.02.008,PMC5400742,,,"Single particle cryo-electron microscopy (cryoEM) is becoming widely adopted as a tool for structural characterization of biomolecules at near-atomic resolution. Vitrification of the sample to obtain a dense distribution of particles within a single field of view remains a major bottleneck for the success of such experiments. Here, we describe a simple and cost-effective method to increase the density of frozen-hydrated particles on grids with holey carbon support films. It relies on performing multiple rounds of sample application and blotting prior to plunge freezing in liquid ethane. We show that this approach is generally applicable and significantly increases particle density for a range of samples, such as small protein complexes, viruses and filamentous assemblies. The method is versatile, easy to implement, minimizes sample requirements and can enable characterization of samples that would otherwise resist structural studies using single particle cryoEM.",,"['Snijder, Joost', 'Borst, Andrew J.', 'Dosey, Annie', 'Walls, Alexandra C.', 'Burrell, Anika', 'Reddy, Vijay S.', 'Kollman, Justin M.', 'Veesler, David']",,,,
,PMC,Germicidal Efficacy and Mammalian Skin Safety of 222-nm UV Light,http://dx.doi.org/10.1667/RR0010CC.1,PMC5552051,,,"We have previously shown that 207-nm ultraviolet (UV) light has similar antimicrobial properties as typical germicidal UV light (254 nm), but without inducing mammalian skin damage. The biophysical rationale is based on the limited penetration distance of 207-nm light in biological samples (e.g. stratum corneum) compared with that of 254-nm light. Here we extended our previous studies to 222-nm light and tested the hypothesis that there exists a narrow wavelength window in the far-UVC region, from around 200–222 nm, which is significantly harmful to bacteria, but without damaging cells in tissues. We used a krypton-chlorine (Kr-Cl) excimer lamp that produces 222-nm UV light with a bandpass filter to remove the lower- and higher-wavelength components. Relative to respective controls, we measured: 1. in vitro killing of methicillin-resistant Staphylococcus aureus (MRSA) as a function of UV fluence; 2. yields of the main UV-associated premutagenic DNA lesions (cyclobutane pyrimidine dimers and 6-4 photoproducts) in a 3D human skin tissue model in vitro; 3. eight cellular and molecular skin damage endpoints in exposed hairless mice in vivo. Comparisons were made with results from a conventional 254-nm UV germicidal lamp used as positive control. We found that 222-nm light kills MRSA efficiently but, unlike conventional germicidal UV lamps (254 nm), it produces almost no premutagenic UV-associated DNA lesions in a 3D human skin model and it is not cytotoxic to exposed mammalian skin. As predicted by biophysical considerations and in agreement with our previous findings, far-UVC light in the range of 200–222 nm kills bacteria efficiently regardless of their drug-resistant proficiency, but without the skin damaging effects associated with conventional germicidal UV exposure.",,"['Buonanno, Manuela', 'Ponnaiya, Brian', 'Welch, David', 'Stanislauskas, Milda', 'Randers-Pehrson, Gerhard', 'Smilenov, Lubomir', 'Lowy, Franklin D.', 'Owens, David M.', 'Brenner, David J.']",,,,
,PMC,Dynamic variations of the peripheral blood immune cell subpopulation in patients with critical H7N9 swine-origin influenza A virus infection: A retrospective small-scale study,http://dx.doi.org/10.3892/etm.2017.4144,PMC5377520,,,"H7N9 influenza is a recently emerging infection with a high mortality rate. The aim of the present study was to investigate dynamic fluctuations of peripheral blood immune cell subgroups in patients with critical H7N9 infection. Flow cytometry was used to assess the cells in whole blood samples from 9 cases. With regard to the innate immune system, in the majority of patients, the natural killer (NK) cell counts were similar to those of monocytes, which demonstrated a gradual increase in the progression period and an early increase followed by a reduction during recovery. B cells exhibited a reduction during progression and were further decreased during recovery. The CD4(+)T cells of all patients decreased during progression, and further decreased during recovery. By contrast, CD8(+)T cells increased in the majority of patients in the progression stage, and underwent an initial reduction followed by a gradual increase during recovery. However, CD8(+) programmed death (PD)-1(+)T cell and T helper (Th) 1 cell frequencies demonstrated a moderate increase in all patients during the progression stage, and regulatory T cell (Treg) frequencies tended to be reduced during progression and increased during recovery. Notably, this preliminary data also showed that the frequencies of B cells, Th2 cells and Th17 cells in the progression period were higher than those in the recovery period. The frequencies of monocytes, CD4(+)T cell, CD8(+)T cell, CD4(+)PD-1(+)T cells and CD8(+)PD-1(+)T cells in the progression period were lower than those during recovery. In conclusion, different levels of peripheral blood immune cell subgroups during the pathogenesis of H7N9 infection may be associated with elimination of the virus and immune damage.",,"['Chen, Cheng', 'Sun, Wei', 'Chen, Jun', 'Huang, Jian-An']",,,,
,PMC,Sequential activation of the three protomers in the Moloney murine leukemia virus Env,http://dx.doi.org/10.1073/pnas.1617264114,PMC5347582,,,"Viral membrane fusion proteins of class I are trimers in which the protomeric unit is a complex of a surface subunit (SU) and a fusion active transmembrane subunit (TM). Here we have studied how the protomeric units of Moloney murine leukemia virus envelope protein (Env) are activated in relation to each other, sequentially or simultaneously. We followed the isomerization of the SU-TM disulfide and subsequent SU release from Env with biochemical methods and found that this early activation step occurred sequentially in the three protomers, generating two asymmetric oligomer intermediates according to the scheme (SU-TM)(3) → (SU-TM)(2)TM → (SU-TM)TM(2) → TM(3). This was the case both when activation was triggered in vitro by depleting stabilizing Ca(2+) from solubilized Env and when viral Env was receptor triggered on rat XC cells. In the latter case, the activation reaction was too fast for direct observation of the intermediates, but they could be caught by alkylation of the isomerization active thiol.",,"['Sjöberg, Mathilda', 'Löving, Robin', 'Lindqvist, Birgitta', 'Garoff, Henrik']",,,,
,PMC,Clinical Significance of Human Coronavirus in Bronchoalveolar Lavage Samples From Hematopoietic Cell Transplant Recipients and Patients With Hematologic Malignancies,http://dx.doi.org/10.1093/cid/cix160,PMC5434339,,,"BACKGROUND. The possible role of human coronavirus (HCoV) in lower respiratory tract disease (LRTD) in hematopoietic cell transplant (HCT) recipients and patients with hematologic malignancies (HM) has not been well studied. METHODS. We conducted a retrospective review of HCT/HM patients with HCoV detected in bronchoalveolar lavage (BAL). HCoV strains were identified in BAL samples using strain-specific polymerase chain reaction. Mortality rates were compared among HCT recipients with LRTD caused by HCoV, respiratory syncytial virus (RSV), influenza virus, or parainfluenza virus (PIV) by multivariable Cox regression analysis. RESULTS. We identified 35 patients (37 episodes) with HCoV LRTD. Among 23 available BAL samples, 48% were strain OC43, 22% were NL63, 17% were 229E, and 13% were HKU1. Overall, 21 patients (60%) required oxygen therapy at diagnosis and 19 (54%) died within 90 days of diagnosis. Respiratory copathogens were detected in 21 episodes (57%), including viruses (n = 12), fungi (n = 10), and bacteria (n = 8). Mortality rates were not different between patients with and without copathogens (P = .65). In multivariable models, mortality associated with HCoV LRTD was similar to that seen with RSV, influenza, and PIV LRTD in HCT recipients (adjusted hazard ratio, 1.34 [95% confidence interval, .66–2.71], P = .41 vs RSV, adjusted for cell source, cytopenia, copathogens, oxygen use, and steroid use). CONCLUSIONS. HCoV LRTD in patients with HCT or HM is associated with high rates of oxygen use and mortality. Mortality associated with HCoV LRTD in HCT recipients appears to be similar to that seen with RSV, influenza virus, and PIV.",,"['Ogimi, Chikara', 'Waghmare, Alpana A.', 'Kuypers, Jane M.', 'Xie, Hu', 'Yeung, Cecilia C.', 'Leisenring, Wendy M.', 'Seo, Sachiko', 'Choi, Su-Mi', 'Jerome, Keith R.', 'Englund, Janet A.', 'Boeckh, Michael']",,,,
,PMC,Determinants of Quality of Life and  Return to Work Following Acute Respiratory Distress Syndrome: A Systematic Review,http://dx.doi.org/10.3238/arztebl.2017.0103,PMC5359461,,,"BACKGROUND: Acute respiratory distress syndrome (ARDS) in adults is a consequence of lung damage caused by either pulmonary or extrapulmonary disease. Survivors often suffer from an impaired health-related quality of life (HRQoL), mental and physical impairments, and persistent inability to work. METHODS: In this systematic review of the literature, we consider the determinants of HRQoL and return to work (RtW). 24 observational studies showing a statistical association between one or more determinants and HRQoL or RtW were included. Because of the heterogeneity of these studies, no statistical aggregation of the individual effect estimates was carried out; instead, the results are summarized descriptively. RESULTS: Psychopathological manifestations, in particular, are associated with impaired quality of life. In contrast, many care- and disease-related determinants had only small, non-significant effects on HRQoL and RtW. The one-second capacity was found in all studies to be positively associated with the HRQoL. ARDS induced by sepsis seems to be a risk factor for a lower HRQoL in comparison to ARDS of other causes. A synthesis of the evidence is impeded both by the high level of heterogeneity of studies and by the high risk of selection bias in all studies. CONCLUSION: The identification of determinants of impaired quality of life after ARDS is essential for the assessment of clinically relevant interventions. In multiple studies, major significant effects were only observed when determinants the content of which was closely related to the scales of the HRQoL instruments were measured at the same time as the HRQoL.",,"['Dodoo-Schittko, Frank', 'Brandstetter, Susanne', 'Blecha, Sebastian', 'Thomann-Hackner, Kathrin', 'Brandl, Magdalena', 'Knüttel, Helge', 'Bein, Thomas', 'Apfelbacher, Christian']",,,,
,PMC,Hendra virus fusion protein transmembrane domain contributes to pre-fusion protein stability,http://dx.doi.org/10.1074/jbc.M117.777235,PMC5392564,,,"Enveloped viruses utilize fusion (F) proteins studding the surface of the virus to facilitate membrane fusion with a target cell membrane. Fusion of the viral envelope with a cellular membrane is required for release of viral genomic material, so the virus can ultimately reproduce and spread. To drive fusion, the F protein undergoes an irreversible conformational change, transitioning from a metastable pre-fusion conformation to a more thermodynamically stable post-fusion structure. Understanding the elements that control stability of the pre-fusion state and triggering to the post-fusion conformation is important for understanding F protein function. Mutations in F protein transmembrane (TM) domains implicated the TM domain in the fusion process, but the structural and molecular details in fusion remain unclear. Previously, analytical ultracentrifugation was utilized to demonstrate that isolated TM domains of Hendra virus F protein associate in a monomer-trimer equilibrium (Smith, E. C., Smith, S. E., Carter, J. R., Webb, S. R., Gibson, K. M., Hellman, L. M., Fried, M. G., and Dutch, R. E. (2013) J. Biol. Chem. 288, 35726–35735). To determine factors driving this association, 140 paramyxovirus F protein TM domain sequences were analyzed. A heptad repeat of β-branched residues was found, and analysis of the Hendra virus F TM domain revealed a heptad repeat leucine-isoleucine zipper motif (LIZ). Replacement of the LIZ with alanine resulted in dramatically reduced TM-TM association. Mutation of the LIZ in the whole protein resulted in decreased protein stability, including pre-fusion conformation stability. Together, our data suggest that the heptad repeat LIZ contributed to TM-TM association and is important for F protein function and pre-fusion stability.",,"['Webb, Stacy', 'Nagy, Tamas', 'Moseley, Hunter', 'Fried, Michael', 'Dutch, Rebecca']",,,,
,PMC,"Targeting phospholipase D in cancer, infection and neurodegenerative disorders",http://dx.doi.org/10.1038/nrd.2016.252,PMC6040825,,,"Lipid second messengers have essential roles in cellular function and contribute to the molecular mechanisms that underlie inflammation, malignant transformation, invasiveness, neurodegenerative disorders, and infectious and other pathophysiological processes. The phospholipase D (PLD) isoenzymes PLD1 and PLD2 are one of the major sources of signal-activated phosphatidic acid (PtdOH) generation downstream of a variety of cell-surface receptors, including G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs) and integrins. Recent advances in the development of isoenzyme-selective PLD inhibitors and in molecular genetics have suggested that PLD isoenzymes in mammalian cells and pathogenic organisms may be valuable targets for the treatment of several human diseases. Isoenzyme-selective inhibitors have revealed complex inter-relationships between PtdOH biosynthetic pathways and the role of PtdOH in pathophysiology. PLD enzymes were once thought to be undruggable owing to the ubiquitous nature of PtdOH in cell signalling and concerns that inhibitors would be too toxic for use in humans. However, recent promising discoveries suggest that small-molecule isoenzyme-selective inhibitors may provide novel compounds for a unique approach to the treatment of cancers, neurodegenerative disorders and other afflictions of the central nervous system, and potentially serve as broad-spectrum antiviral and antimicrobial therapeutics.",,"['Brown, H. Alex', 'Thomas, Paul G.', 'Lindsley, Craig W.']",,,,
,PMC,SARS-CoV-Encoded Small RNAs Contribute to Infection-Associated Lung Pathology,http://dx.doi.org/10.1016/j.chom.2017.01.015,PMC5662013,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) causes lethal disease in humans, which is characterized by exacerbated inflammatory response and extensive lung pathology. To address the relevance of small non-coding RNAs in SARS-CoV pathology, we deep sequenced RNAs from the lungs of infected mice and discovered three 18–22 nt small viral RNAs (svRNAs). The three svRNAs were derived from the nsp3 (svRNA-nsp3.1 and -nsp3.2) and N (svRNA-N) genomic regions of SARS-CoV. Biogenesis of CoV svRNAs was RNase III, cell type, and host species independent, but it was dependent on the extent of viral replication. Antagomir-mediated inhibition of svRNA-N significantly reduced in vivo lung pathology and pro-inflammatory cytokine expression. Taken together, these data indicate that svRNAs contribute to SARS-CoV pathogenesis and highlight the potential of svRNA-N antagomirs as antivirals.",,"['Morales, Lucía', 'Oliveros, Juan Carlos', 'Fernandez-Delgado, Raúl', 'tenOever, Benjamin Robert', 'Enjuanes, Luis', 'Sola, Isabel']",,,,
,PMC,"Inference and forecast of H7N9 influenza in China, 2013 to 2015",http://dx.doi.org/10.2807/1560-7917.ES.2017.22.7.30462,PMC5322186,28230525,CC BY,"The recent emergence of A(H7N9) avian influenza poses a significant challenge to public health in China and around the world; however, understanding of the transmission dynamics and progression of influenza A(H7N9) infection in domestic poultry, as well as spillover transmission to humans, remains limited. Here, we develop a mathematical model–Bayesian inference system which combines a simple epidemic model and data assimilation method, and use it in conjunction with data on observed human influenza A(H7N9) cases from 19 February 2013 to 19 September 2015 to estimate key epidemiological parameters and to forecast infection in both poultry and humans. Our findings indicate a high outbreak attack rate of 33% among poultry but a low rate of chicken-to-human spillover transmission. In addition, we generated accurate forecasts of the peak timing and magnitude of human influenza A(H7N9) cases. This work demonstrates that transmission dynamics within an avian reservoir can be estimated and that real-time forecast of spillover avian influenza in humans is possible.",2017 Feb 16,"['Li, Ruiyun', 'Bai, Yuqi', 'Heaney, Alex', 'Kandula, Sasikiran', 'Cai, Jun', 'Zhao, Xuyi', 'Xu, Bing', 'Shaman, Jeffrey']",Euro Surveill,,,
,PMC,Severity of Respiratory Syncytial Virus Lower Respiratory Tract Infection With Viral Coinfection in HIV-Uninfected Children,http://dx.doi.org/10.1093/cid/ciw756,PMC5712444,,,"BACKGROUND: Molecular diagnostics enable sensitive detection of respiratory viruses, but their clinical significance remains unclear in pediatric lower respiratory tract infection (LRTI). We aimed to determine whether viral coinfections increased life-threatening disease in a large cohort. METHODS: Molecular testing was performed for respiratory viruses in nasopharyngeal aspirates collected from children aged <5 years within 24 hours of hospital admission during sentinel surveillance for severe acute respiratory illness (SARI) hospitalization conducted in South Africa during February 2009–December 2013. The primary outcome was life-threatening disease, defined as mechanical ventilation, intensive care unit admission, or death. RESULTS: Of 2322 HIV-uninfected children with respiratory syncytial virus (RSV)–associated LRTI, 1330 (57.3%) had RSV monoinfection, 38 (1.6%) had life-threatening disease, 575 (24.8%) had rhinovirus, 347 (14.9%) had adenovirus (ADV), and 30 (1.3%) had influenza virus. RSV and any other viral coinfection was not associated with severe disease (odds ratio [OR], 1.4; 95% confidence interval [CI], OR, 0.74; 95% CI, .39–1.4), ADV coinfection had increased odds of life-threatening disease (adjusted OR, 3.4; 95% CI, 1.6–7.2; P = .001), and influenza coinfection had increased odds of life-threatening disease and prolonged length of stay (adjusted OR, 2.1; 95% CI, 1.0–4.5; P = .05) compared with RSV monoinfection. CONCLUSIONS: RSV coinfection with any respiratory virus is not associated with more severe disease when compared to RSV alone in this study. However, increased life-threatening disease in RSV-ADV and RSV-influenza coinfection warrants further study.",,"['Mazur, Natalie I.', 'Bont, Louis', 'Cohen, Adam L.', 'Cohen, Cheryl', 'von Gottberg, Anne', 'Groome, Michelle J.', 'Hellferscee, Orienka', 'Klipstein-Grobusch, Kerstin', 'Mekgoe, Omphile', 'Naby, Fathima', 'Moyes, Jocelyn', 'Tempia, Stefano', 'Treurnicht, Florette K.', 'Venter, Marietje', 'Walaza, Sibongile', 'Wolter, Nicole', 'Madhi, Shabir A.', None]",,,,
,PMC,Panblok-H1+advax H1N1/2009pdm vaccine: Insights into rapid development of a delta inulin adjuvanted recombinant pandemic influenza vaccine,http://dx.doi.org/10.1080/21645515.2017.1279765,PMC5489286,,,"Timely vaccine supply is critical during influenza pandemics but is impeded by current virus-based manufacturing methods. The 2009 H1N1/2009pdm ‘swine flu’ pandemic reinforced the need for innovation in pandemic vaccine design. We report on insights gained during rapid development of a pandemic vaccine based on recombinant haemagglutinin (rHA) formulated with Advax™ delta inulin adjuvant (Panblok-H1/Advax). Panblok-H1/Advax was designed and manufactured within 1 month of the pandemic declaration by WHO and successfully entered human clinical testing in under 3 months from first isolation and sequencing of the novel pandemic virus, requiring several major challenges to be overcome. Panblok-H1/Advax successfully induced neutralising antibodies against the pandemic strain, but also induced cross-neutralising antibodies in a subset of subjects against an H1N1 strain (A/Puerto Rico/8/34) derived from the 1918 Spanish flu, highlighting the possibility to use Advax to induce more broadly cross-protective antibody responses. Interestingly, the rHA from H1N1/2009pdm exhibited variants in the receptor binding domain that had a major impact on receptor binding and hemagglutination ability. We used an in silico structural modeling approach to better understand the unusual behavior of the novel hemagglutinin, thereby demonstrating the power of computational modeling approaches for rapid characterization of new pandemic viruses. While challenges remain in ensuring ultrafast vaccine access for the entire population in response to future pandemics, the adjuvanted recombinant Panblok-H1/Advax vaccine proved its utility during a real-life pandemic situation.",,"['Honda-Okubo, Yoshikazu', 'Rajapaksha, Harinda', 'Sajkov, Dimitar', 'Gordon, David', 'Cox, Manon M. J.', 'Petrovsky, Nikolai']",,,,
,PMC,Channel-Inactivating Mutations and Their Revertant Mutants in the Envelope Protein of Infectious Bronchitis Virus,http://dx.doi.org/10.1128/JVI.02158-16,PMC5309962,,,"It has been shown previously in the severe acute respiratory syndrome coronavirus (SARS-CoV) that two point mutations, N15A and V25F, in the transmembrane domain (TMD) of the envelope (E) protein abolished channel activity and led to in vivo attenuation. Pathogenicity was recovered in mutants that also regained E protein channel activity. In particular, V25F was rapidly compensated by changes at multiple V25F-facing TMD residues located on a neighboring monomer, consistent with a recovery of oligomerization. Here, we show using infected cells that the same mutations, T16A and A26F, in the gamma-CoV infectious bronchitis virus (IBV) lead to, in principle, similar results. However, IBV E A26F did not abolish oligomer formation and was compensated by mutations at N- and C-terminal extramembrane domains (EMDs). The C-terminal EMD mutations clustered along an insertion sequence specific to gamma-CoVs. Nuclear magnetic resonance data are consistent with the presence of only one TMD in IBV E, suggesting that recovery of channel activity and fitness in these IBV E revertant mutants is through an allosteric interaction between EMDs and TMD. The present results are important for the development of IBV live attenuated vaccines when channel-inactivating mutations are introduced in the E protein. IMPORTANCE The ion channel activity of SARS-CoV E protein is a determinant of virulence, and abolishment of channel activity leads to viral attenuation. E deletion may be a strategy for generating live attenuated vaccines but can trigger undesirable compensatory mechanisms through modifications of other viral proteins to regain virulence. Therefore, a more suitable approach may be to introduce small but critical attenuating mutations. For this, the stability of attenuating mutations should be examined to understand the mechanisms of reversion. Here, we show that channel-inactivating mutations of the avian infectious bronchitis virus E protein introduced in a recombinant virus system are deficient in viral release and fitness and that revertant mutations also restored channel activity. Unexpectedly, most of the revertant mutations appeared at extramembrane domains, particularly along an insertion specific for gammacoronaviruses. Our structural data propose a single transmembrane domain in IBV E, suggesting an allosteric interaction between extramembrane and transmembrane domains.",,"['To, Janet', 'Surya, Wahyu', 'Fung, To Sing', 'Li, Yan', 'Verdià-Bàguena, Carmina', 'Queralt-Martin, Maria', 'Aguilella, Vicente M.', 'Liu, Ding Xiang', 'Torres, Jaume']",,,,
,PMC,Surveillance of Bat Coronaviruses in Kenya Identifies Relatives of Human Coronaviruses NL63 and 229E and Their Recombination History,http://dx.doi.org/10.1128/JVI.01953-16,PMC5309958,,,"Bats harbor a large diversity of coronaviruses (CoVs), several of which are related to zoonotic pathogens that cause severe disease in humans. Our screening of bat samples collected in Kenya from 2007 to 2010 not only detected RNA from several novel CoVs but, more significantly, identified sequences that were closely related to human CoVs NL63 and 229E, suggesting that these two human viruses originate from bats. We also demonstrated that human CoV NL63 is a recombinant between NL63-like viruses circulating in Triaenops bats and 229E-like viruses circulating in Hipposideros bats, with the breakpoint located near 5′ and 3′ ends of the spike (S) protein gene. In addition, two further interspecies recombination events involving the S gene were identified, suggesting that this region may represent a recombination “hot spot” in CoV genomes. Finally, using a combination of phylogenetic and distance-based approaches, we showed that the genetic diversity of bat CoVs is primarily structured by host species and subsequently by geographic distances. IMPORTANCE Understanding the driving forces of cross-species virus transmission is central to understanding the nature of disease emergence. Previous studies have demonstrated that bats are the ultimate reservoir hosts for a number of coronaviruses (CoVs), including ancestors of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and human CoV 229E (HCoV-229E). However, the evolutionary pathways of bat CoVs remain elusive. We provide evidence for natural recombination between distantly related African bat coronaviruses associated with Triaenops afer and Hipposideros sp. bats that resulted in a NL63-like virus, an ancestor of the human pathogen HCoV-NL63. These results suggest that interspecies recombination may play an important role in CoV evolution and the emergence of novel CoVs with zoonotic potential.",,"['Tao, Ying', 'Shi, Mang', 'Chommanard, Christina', 'Queen, Krista', 'Zhang, Jing', 'Markotter, Wanda', 'Kuzmin, Ivan V.', 'Holmes, Edward C.', 'Tong, Suxiang']",,,,
,PMC,Lineage A Betacoronavirus NS2 Proteins and the Homologous Torovirus Berne pp1a Carboxy-Terminal Domain Are Phosphodiesterases That Antagonize Activation of RNase L,http://dx.doi.org/10.1128/JVI.02201-16,PMC5309944,,,"Viruses in the family Coronaviridae, within the order Nidovirales, are etiologic agents of a range of human and animal diseases, including both mild and severe respiratory diseases in humans. These viruses encode conserved replicase and structural proteins as well as more diverse accessory proteins, encoded in the 3′ ends of their genomes, that often act as host cell antagonists. We previously showed that 2′,5′-phosphodiesterases (2′,5′-PDEs) encoded by the prototypical Betacoronavirus, mouse hepatitis virus (MHV), and by Middle East respiratory syndrome-associated coronavirus antagonize the oligoadenylate-RNase L (OAS-RNase L) pathway. Here we report that additional coronavirus superfamily members, including lineage A betacoronaviruses and toroviruses infecting both humans and animals, encode 2′,5′-PDEs capable of antagonizing RNase L. We used a chimeric MHV system (MHV(Mut)) in which exogenous PDEs were expressed from an MHV backbone lacking the gene for a functional NS2 protein, the endogenous RNase L antagonist. With this system, we found that 2′,5′-PDEs encoded by the human coronavirus HCoV-OC43 (OC43; an agent of the common cold), human enteric coronavirus (HECoV), equine coronavirus (ECoV), and equine torovirus Berne (BEV) are enzymatically active, rescue replication of MHV(Mut) in bone marrow-derived macrophages, and inhibit RNase L-mediated rRNA degradation in these cells. Additionally, PDEs encoded by OC43 and BEV rescue MHV(Mut) replication and restore pathogenesis in wild-type (WT) B6 mice. This finding expands the range of viruses known to encode antagonists of the potent OAS-RNase L antiviral pathway, highlighting its importance in a range of species as well as the selective pressures exerted on viruses to antagonize it. IMPORTANCE Viruses in the family Coronaviridae include important human and animal pathogens, including the recently emerged viruses severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and Middle East respiratory syndrome-associated coronavirus (MERS-CoV). We showed previously that two viruses within the genus Betacoronavirus, mouse hepatitis virus (MHV) and MERS-CoV, encode 2′,5′-phosphodiesterases (2′,5′-PDEs) that antagonize the OAS-RNase L pathway, and we report here that these proteins are furthermore conserved among additional coronavirus superfamily members, including lineage A betacoronaviruses and toroviruses, suggesting that they may play critical roles in pathogenesis. As there are no licensed vaccines or effective antivirals against human coronaviruses and few against those infecting animals, identifying viral proteins contributing to virulence can inform therapeutic development. Thus, this work demonstrates that a potent antagonist of host antiviral defenses is encoded by multiple and diverse viruses within the family Coronaviridae, presenting a possible broad-spectrum therapeutic target.",,"['Goldstein, Stephen A.', 'Thornbrough, Joshua M.', 'Zhang, Rong', 'Jha, Babal K.', 'Li, Yize', 'Elliott, Ruth', 'Quiroz-Figueroa, Katherine', 'Chen, Annie I.', 'Silverman, Robert H.', 'Weiss, Susan R.']",,,,
,PMC,Binding of the Methyl Donor S-Adenosyl-l-Methionine to Middle East Respiratory Syndrome Coronavirus 2′-O-Methyltransferase nsp16 Promotes Recruitment of the Allosteric Activator nsp10,http://dx.doi.org/10.1128/JVI.02217-16,PMC5309940,,,"The Middle East respiratory syndrome coronavirus (MERS-CoV) nonstructural protein 16 (nsp16) is an S-adenosyl-l-methionine (SAM)-dependent 2′-O-methyltransferase (2′-O-MTase) that is thought to methylate the ribose 2′-OH of the first transcribed nucleotide (N(1)) of viral RNA cap structures. This 2′-O-MTase activity is regulated by nsp10. The 2′-O methylation prevents virus detection by cell innate immunity mechanisms and viral translation inhibition by the interferon-stimulated IFIT-1 protein. To unravel the regulation of nsp10/nsp16 2′-O-MTase activity, we used purified MERS-CoV nsp16 and nsp10. First, we showed that nsp16 recruited N7-methylated capped RNA and SAM. The SAM binding promotes the assembly of the enzymatically active nsp10/nsp16 complex that converted (7m)GpppG (cap-0) into (7m)GpppG(2′Om) (cap-1) RNA by 2′-OH methylation of N(1) in a SAM-dependent manner. The subsequent release of SAH speeds up nsp10/nsp16 dissociation that stimulates the reaction turnover. Alanine mutagenesis and RNA binding assays allowed the identification of the nsp16 residues involved in RNA recognition forming the RNA binding groove (K46, K170, E203, D133, R38, Y47, and Y181) and the cap-0 binding site (Y30, Y132, and H174). Finally, we found that nsp10/nsp16 2′-O-MTase activity is sensitive to known MTase inhibitors, such as sinefungin and cap analogues. This characterization of the MERS-CoV 2′-O-MTase is a preliminary step toward the development of molecules to inhibit cap 2′-O methylation and to restore the host antiviral response. IMPORTANCE MERS-CoV codes for a cap 2′-O-methyltransferase that converts cap-0 into cap-1 structure in order to prevent virus detection by cell innate immunity mechanisms. We report the biochemical properties of MERS-CoV 2′O-methyltransferase, which is stimulated by nsp10 acting as an allosteric activator of the nsp16 2′-O-methyltransferase possibly through enhanced RNA binding affinity. In addition, we show that SAM promotes the formation of the active nsp10/nsp16 complex. Conversely, after cap methylation, the reaction turnover is speeded up by cap-1 RNA release and nsp10/nsp16 complex dissociation, at the low intracellular SAH concentration. These results suggest that SAM/SAH balance is a regulator of the 2′-O-methyltransferase activity and raises the possibility that SAH hydrolase inhibitors might interfere with CoV replication cycle. The enzymatic and RNA binding assays developed in this work were also used to identify nsp16 residues involved in cap-0 RNA recognition and to understand the action mode of known methyltransferase inhibitors.",,"['Aouadi, Wahiba', 'Blanjoie, Alexandre', 'Vasseur, Jean-Jacques', 'Debart, Françoise', 'Canard, Bruno', 'Decroly, Etienne']",,,,
,PMC,Ribosome Profiling Reveals Translational Upregulation of Cellular Oxidative Phosphorylation mRNAs during Vaccinia Virus-Induced Host Shutoff,http://dx.doi.org/10.1128/JVI.01858-16,PMC5309933,,,"Vaccinia virus infection causes a host shutoff that is marked by global inhibition of host protein synthesis. Though the host shutoff may facilitate reallocation of cellular resources for viral replication and evasion of host antiviral immune responses, it poses a challenge for continuous synthesis of cellular proteins that are important for viral replication. It is, however, unclear whether and how certain cellular proteins may be selectively synthesized during the vaccinia virus-induced host shutoff. Using simultaneous RNA sequencing and ribosome profiling, two techniques quantifying genome-wide levels of mRNA and active protein translation, respectively, we analyzed the responses of host cells to vaccinia virus infection at both the transcriptional and translational levels. The analyses showed that cellular mRNA depletion played a dominant role in the shutoff of host protein synthesis. Though the cellular mRNAs were significantly reduced, the relative translation efficiency of a subset of cellular mRNAs increased, particularly those involved in oxidative phosphorylation that are responsible for cellular energy production. Further experiments demonstrated that the protein levels and activities of oxidative phosphorylation increased during vaccinia virus infection, while inhibition of the cellular oxidative phosphorylation function significantly suppressed vaccinia virus replication. Moreover, the short 5′ untranslated region of the oxidative phosphorylation mRNAs contributed to the translational upregulation. These results provide evidence of a mechanism that couples translational control and energy metabolism, two processes that all viruses depend on host cells to provide, to support vaccinia virus replication during a host shutoff. IMPORTANCE Many viral infections cause global host protein synthesis shutoff. While host protein synthesis shutoff benefits the virus by relocating cellular resources to viral replication, it also poses a challenge to the maintenance of cellular functions necessary for viral replication if continuous protein synthesis is required. Here we measured the host mRNA translation rate during a vaccinia virus-induced host shutoff by analyzing total and actively translating mRNAs in a genome-wide manner. This study revealed that oxidative phosphorylation mRNAs were translationally upregulated during vaccinia virus-induced host protein synthesis shutoff. Oxidative phosphorylation is the major cellular energy-producing pathway, and we further showed that maintenance of its function is important for vaccinia virus replication. This study highlights the fact that vaccinia virus infection can enhance cellular energy production through translational upregulation in the context of an overall host protein synthesis shutoff to meet energy expenditure.",,"['Dai, Aimei', 'Cao, Shuai', 'Dhungel, Pragyesh', 'Luan, Yizhao', 'Liu, Yizhi', 'Xie, Zhi', 'Yang, Zhilong']",,,,
,PMC,Prioritizing the ‘Dormant’ Flaviviruses,http://dx.doi.org/10.1007/s10393-017-1220-6,PMC5386397,,,,,"['Olival, Kevin J.', 'Willoughby, Anna R.']",,,,
,PMC,Spatial and temporal dynamics of superspreading events in the 2014–2015 West Africa Ebola epidemic,http://dx.doi.org/10.1073/pnas.1614595114,PMC5338479,,,"The unprecedented scale of the Ebola outbreak in Western Africa (2014–2015) has prompted an explosion of efforts to understand the transmission dynamics of the virus and to analyze the performance of possible containment strategies. Models have focused primarily on the reproductive numbers of the disease that represent the average number of secondary infections produced by a random infectious individual. However, these population-level estimates may conflate important systematic variation in the number of cases generated by infected individuals, particularly found in spatially localized transmission and superspreading events. Although superspreading features prominently in first-hand narratives of Ebola transmission, its dynamics have not been systematically characterized, hindering refinements of future epidemic predictions and explorations of targeted interventions. We used Bayesian model inference to integrate individual-level spatial information with other epidemiological data of community-based (undetected within clinical-care systems) cases and to explicitly infer distribution of the cases generated by each infected individual. Our results show that superspreaders play a key role in sustaining onward transmission of the epidemic, and they are responsible for a significant proportion ([Formula: see text] 61%) of the infections. Our results also suggest age as a key demographic predictor for superspreading. We also show that community-based cases may have progressed more rapidly than those notified within clinical-care systems, and most transmission events occurred in a relatively short distance (with median value of 2.51 km). Our results stress the importance of characterizing superspreading of Ebola, enhance our current understanding of its spatiotemporal dynamics, and highlight the potential importance of targeted control measures.",,"['Lau, Max S. Y.', 'Dalziel, Benjamin Douglas', 'Funk, Sebastian', 'McClelland, Amanda', 'Tiffany, Amanda', 'Riley, Steven', 'Metcalf, C. Jessica E.', 'Grenfell, Bryan T.']",,,,
,PMC,"Seasonal variations in transition, mortality and kidney transplantation among patients with end-stage renal disease in the USA",http://dx.doi.org/10.1093/ndt/gfw379,PMC6557195,,,"BACKGROUND: Seasonal variations may exist in transitioning to dialysis, kidney transplantation and related outcomes among end-stage renal disease (ESRD) patients. Elucidating these variations may have major clinical and healthcare policy implications for better resource allocation across seasons. METHODS: Using the United States Renal Data System database from 1 January 2000 to 31 December 2013, we calculated monthly counts of transitioning to dialysis or first transplantation and deaths. Crude monthly transition fraction was defined as the number of new ESRD patients divided by all ESRD patients on the first day of each month. Similar fractions were calculated for all-cause and cause-specific mortality and transplantation. RESULTS: The increasing trend of the annual transition to ESRD plateaued during 2009–2012 (n = 126 264), and dropped drastically in 2013 (n = 117 372). Independent of secular trends, monthly transition to ESRD was lowest in July (1.65%) and highest in January (1.97%) of each year. All-cause, cardiovascular and infectious mortalities were lowest in July or August (1.32, 0.58 and 0.15%, respectively) and highest in January (1.56, 0.71 and 0.19%, respectively). Kidney transplantation was highest in June (0.33%), and this peak was mainly attributed to living kidney transplantation in summer months. Transplant failure showed a similar seasonal variation to naïve transition, peaking in January (0.65%) and nadiring in September (0.56%). CONCLUSIONS: Transitioning to ESRD and adverse events among ESRD people were more frequent in winter and less frequent in summer, whereas kidney transplantation showed the reverse trend. The potential causes and implications of these consistent seasonal variations warrant more investigation.",,"['Obi, Yoshitsugu', 'Kalantar-Zadeh, Kamyar', 'Streja, Elani', 'Rhee, Connie M.', 'Reddy, Uttam G.', 'Soohoo, Melissa', 'Wang, Yaping', 'Ravel, Vanessa', 'You, Amy S.', 'Jing, Jennie', 'Sim, John J.', 'Nguyen, Danh V.', 'Gillen, Daniel L.', 'Saran, Rajiv', 'Robinson, Bruce', 'Kovesdy, Csaba P.']",,,,
,PMC,Massive plasmablast response elicited in the acute phase of hantavirus pulmonary syndrome,http://dx.doi.org/10.1111/imm.12713,PMC5382343,,,"Beside its key diagnostic value, the humoral immune response is thought to play a protective role in hantavirus pulmonary syndrome. However, little is known about the cell source of these antibodies during ongoing human infection. Herein we characterized B‐cell subsets circulating in Andes‐virus‐infected patients. A notable potent plasmablast (PB) response that increased 100‐fold over the baseline levels was observed around 1 week after the onset of symptoms. These PB present a CD3(neg) CD19(low) CD20(neg) CD38(hi) CD27(hi) CD138(+/−) IgA(+/−) surface phenotype together with the presence of cytoplasmic functional immunoglobulins. They are large lymphocytes (lymphoblasts) morphologically coincident with the ‘immunoblast‐like’ cells that have been previously described during blood cytology examinations of hantavirus‐infected patients. Immunoreactivity analysis of white blood cell lysates suggests that some circulating PB are virus‐specific but we also observed a significant increase of reactivity against virus‐unrelated antigens, which suggests a possible bystander effect by polyclonal B‐cell activation. The presence of this large and transient PB response raises the question as to whether these cells might have a protective or pathological role during the ongoing hantavirus pulmonary syndrome and suggest their practical application as a diagnostic/prognostic biomarker.",,"['García, Marina', 'Iglesias, Ayelén', 'Landoni, Verónica I.', 'Bellomo, Carla', 'Bruno, Agostina', 'Córdoba, María Teresa', 'Balboa, Luciana', 'Fernández, Gabriela C.', 'Sasiain, María del Carmen', 'Martínez, Valeria P.', 'Schierloh, Pablo']",,,,
,PMC,Middle East Respiratory Syndrome,http://dx.doi.org/10.1056/NEJMsr1408795,PMC5362064,,,"Between September 2012 and January 20, 2017, the World Health Organization (WHO) received reports from 27 countries of 1879 laboratory-confirmed cases in humans of the Middle East respiratory syndrome (MERS) caused by infection with the MERS coronavirus (MERS-CoV) and at least 659 related deaths. Cases of MERS-CoV infection continue to occur, including sporadic zoonotic infections in humans across the Arabian Peninsula, occasional importations and associated clusters in other regions, and outbreaks of nonsustained human-to-human transmission in health care settings. Dromedary camels are considered to be the most likely source of animal-to-human transmission. MERS-CoV enters host cells after binding the dipeptidyl peptidase 4 (DPP-4) receptor and the carcinoembryonic antigen–related cell-adhesion molecule 5 (CEACAM5) cofactor ligand, and it replicates efficiently in the human respiratory epithelium. Illness begins after an incubation period of 2 to 14 days and frequently results in hypoxemic respiratory failure and the need for multiorgan support. However, asymptomatic and mild cases also occur. Real-time reverse-transcription–polymerase-chain-reaction (RT-PCR) testing of respiratory secretions is the mainstay for diagnosis, and samples from the lower respiratory tract have the greatest yield among seriously ill patients. There is no antiviral therapy of proven efficacy, and thus treatment remains largely supportive; potential vaccines are at an early developmental stage. There are multiple gaps in knowledge regarding the evolution and transmission of the virus, disease pathogenesis, treatment, and prospects for a vaccine. The ongoing occurrence of MERS in humans and the associated high mortality call for a continued collaborative approach toward gaining a better understanding of the infection both in humans and in animals. MERS-CoV was first identified in September 20121 in a patient from Saudi Arabia who had hypoxemic respiratory failure and multiorgan illness. Subsequent cases have included infections in humans across the Arabian Peninsula, occasional importations and associated clusters in other regions, and outbreaks of nonsustained human-to-human transmission in health care settings (Fig. 1).",,"['Arabi, Yaseen M.', 'Balkhy, Hanan H.', 'Hayden, Frederick G.', 'Bouchama, Abderrezak', 'Luke, Thomas', 'Baillie, J. Kenneth', 'Al-Omari, Awad', 'Hajeer, Ali H.', 'Senga, Mikiko', 'Denison, Mark R.', 'Nguyen-Van-Tam, Jonathan S.', 'Shindo, Nahoko', 'Bermingham, Alison', 'Chappell, James D.', 'Van Kerkhove, Maria D.', 'Fowler, Robert A.']",,,,
,PMC,Burden of Human Metapneumovirus Infections in Cancer Patients: Risk Factors and Outcomes,http://dx.doi.org/10.1002/cncr.30599,PMC5459658,,,"BACKGROUND: Human metapneumovirus (hMPV) causes upper and lower respiratory tract infections (URI and LRI, respectively) in healthy and immunocompromised patients; however, its clinical burden in patients with cancer remains unknown. METHODS: In a retrospective study of all laboratory-confirmed hMPV infections treated at our institution between April 2012 and May 2015, we determined clinical characteristics, risk factors for progression to LRI, treatment, and outcomes in patients with cancer. RESULTS: We identified 181 hMPV infections in 90 (50%) patients with hematologic malignancies (HM), 57 (31%) hematopoietic cell transplantation (HCT) recipients, and 34 patients (19%) with solid tumors. Most patients (92%) had a community-acquired infection, presented with URI (67%), and 43% developed LRI (59 presented with LRI and 19 progressed from URI to LRI). On multivariable analysis, an underlying HM (adjusted odds ratio [aOR], 3.11(1.12-8.64); P=0.029), nosocomial infection (aOR, 26.9 (2.79-259.75); P=0.004), and hypoxia (SpO2 ≤ 92%) at presentation (aOR, 9.61(1.98-46.57); P = 0.005) were independent factors associated with LRI. All-cause mortality at 30 days from hMPV diagnosis was low (4%) and patients with LRI had a 10% mortality rate at day 30 from diagnosis; whereas, patients with URI had 0% mortality rate. CONCLUSIONS: hMPV infections in patients with cancer may cause significant morbidity, especially for those with underlying HM who may develop an LRI. Despite high morbidity and the lack of directed antiviral therapy for hMPV infections, mortality at day 30 from this infection remained low in this studied population.",,"['Chaer, Firas El', 'Shah, Dimpy P.', 'Kmeid, Joumana', 'Ariza-Heredia, Ella', 'Hosing, Chitra M.', 'Mulanovich, Victor', 'Chemaly, Roy F.']",,,,
,PMC,VIRAL POLYMERASES,http://dx.doi.org/10.1016/j.virusres.2017.02.003,PMC5710837,,,,,"['Menéndez-Arias, Luis', 'Andino, Raul']",,,,
,PMC,Airway and Serum Biochemical Correlates of Refractory Neutrophilic Asthma,http://dx.doi.org/10.1016/j.jaci.2016.12.963,PMC5540819,,,"BACKGROUND: Despite the progress in diagnosis and management of asthma, many patients have poorly controlled or refractory asthma. The mechanism of this refractory asthma is not well understood. OBJECTIVE: Explore the relationship between neutrophils and other biomarkers of refractory asthma. METHOD: Sixty subjects with refractory asthma (RA), 30 with non-refractory asthma (NRA) and 20 healthy subjects were enrolled. We performed a comprehensive characterization of these study subjects, which included laboratory and pulmonary function studies, chest CT, and bronchoscopy with bronchoalveolar lavage. We analyzed BAL and serum for a total of 244 biomolecules by multiplex assay and correlated them with the clinical and other laboratory parameters. RESULTS: RA was significantly different from NRA with regard to pulmonary function indices, bronchial basement membrane thickness, and BAL neutrophils and lymphocytes but not eosinophils. BAL neutrophils negatively and positively correlated with the forced vital capacity and age, respectively. Of the 244 biomolecules studied, 52 and 14 biomolecules from BAL and serum, respectively, were significantly different among the study groups. Thirteen of these 52 molecules correlated with BAL neutrophils. BAL from 40% of RA patients was positive for a pathogenic microbe. Infection-negative neutrophilic RA was associated with an increase in select biomarkers of inflammation in the serum suggesting the presence of systemic inflammation. CONCLUSIONS: RA was associated with increased number of neutrophils and proneutrophilic biomolecules in the airways. Subclinical infection was present in 40% of RA patients, which likely contributed to neutrophilic inflammation. A subgroup of non-infected neutrophilic RA was associated with systemic inflammation.",,"['Alam, Rafeul', 'Good, James', 'Rollins, Donald', 'Verma, Mukesh', 'Chu, HongWei', 'Pham, Tuyet-Hang', 'Martin, Richard J.']",,,,
,PMC,What Kaplan-Meier Survival Curves Don’t Tell Us About CNS Disease,http://dx.doi.org/10.1016/j.jneuroim.2017.01.020,PMC5474346,,,"Central nervous system consequences of viral infections are rare, but when they do occur, they are often serious and clinically challenging to manage. Our awareness of the perils of neuroinvasion by viruses is growing: the recently appreciated impact of Ebola and Zika virus infections on CNS integrity, decreases in vaccination coverage for potentially neurotropic viruses such as measles, and increased neurovirulence of some influenza strains collectively highlight the need for a better understanding of the viral-neural interaction. Defining these interactions and how they result in neuropathogenesis is paramount for the development of better clinical strategies, especially given the limited treatment options that are available due to the unique physiology of the brain that limits migration of blood-borne molecules into the CNS parenchyma. In this perspective, we discuss some unique aspects of neuronal viral infections and immune-mediated control that impact the pathogenic outcomes of these infections. Further, we draw attention to an often overlooked aspect of neuropathogenesis research: that lack of overt disease, which is often equated with survival post-infection, likely only scratches the surface of the myriad ways by which neurotropic infections can impair CNS function.",,"['Miller, Katelyn D.', 'Rall, Glenn F.']",,,,
,PMC,Procalcitonin Accurately Identifies Hospitalized Children With Low Risk of Bacterial Community-Acquired Pneumonia,http://dx.doi.org/10.1093/jpids/piw091,PMC6251689,,,"BACKGROUND: Lower procalcitonin (PCT) concentrations are associated with reduced risk of bacterial community-acquired pneumonia (CAP) in adults, but data in children are limited. METHODS: We analyzed serum PCT concentrations from children hospitalized with radiographically confirmed CAP enrolled in the Centers for Disease Control and Prevention’s Etiology of Pneumonia in the Community (EPIC) Study. Blood and respiratory specimens were tested using multiple pathogen detection methods for typical bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus), atypical bacteria (Mycoplasma pneumoniae and Chlamydophila pneumoniae), and respiratory viruses. Multivariable regression was used to assess associations between PCT concentrations and etiology and severity. RESULTS: Among 532 children (median age, 2.4 years; interquartile range [IQR], 1.0–6.3), patients with typical bacteria had higher PCT concentrations (±viruses; n = 54; median, 6.10; IQR, 0.84–22.79 ng/mL) than those with atypical bacteria (±viruses; n = 82; median, 0.10; IQR, 0.06–0.39 ng/mL), viral pathogens only (n = 349; median, 0.33; IQR, 0.12–1.35 ng/mL), or no pathogen detected (n = 47; median, 0.44; IQR, 0.10–1.83 ng/mL) (P < .001 for all). No child with PCT <0.1 ng/mL had typical bacteria detected. Procalcitonin <0.25 ng/mL featured a 96% negative predictive value (95% confidence interval [CI], 93–99), 85% sensitivity (95% CI, 76–95), and 45% specificity (95% CI, 40–50) in identifying children without typical bacterial CAP. CONCLUSIONS: Lower PCT concentrations in children hospitalized with CAP were associated with a reduced risk of typical bacterial detection and may help identify children who would not benefit from antibiotic treatment.",,"['Stockmann, Chris', 'Ampofo, Krow', 'Killpack, Jarrett', 'Williams, Derek J', 'Edwards, Kathryn M', 'Grijalva, Carlos G', 'Arnold, Sandra R', 'McCullers, Jonathan A', 'Anderson, Evan J', 'Wunderink, Richard G', 'Self, Wesley H', 'Bramley, Anna', 'Jain, Seema', 'Pavia, Andrew T', 'Blaschke, Anne J']",,,,
,PMC,Computational de novo Design of Antibodies binding to a Peptide with High Affinity,http://dx.doi.org/10.1002/bit.26244,PMC5726764,,,"Antibody drugs play a critical role in infectious diseases, cancer, autoimmune diseases, and inflammation. However, experimental methods for the generation of therapeutic antibodies such as using immunized mice or directed evolution remain time consuming and cannot target a specific antigen epitope. Here, we describe the application of a computational framework called OptMAVEn combined with molecular dynamics to de novo design antibodies. Our reference system is antibody 2D10, a single-chain antibody (scFv) that recognizes the dodecapeptide DVFYPYPYASGS, a peptide mimic of mannose-containing carbohydrates. Five de novo designed scFvs sharing less than 75% sequence similarity to all existing natural antibody sequences were generated using OptMAVEn and their binding to the dodecapeptide was experimentally characterized by biolayer interferometry and isothermal titration calorimetry. Among them, three scFvs show binding affinity to the dodecapeptide at the nM level. Critically, these de novo designed scFvs exhibit considerably diverse modeled binding modes with the dodecapeptide. The results demonstrate the potential of OptMAVEn for the de novo design of thermally and conformationally stable antibodies with high binding affinity to antigens and encourage the targeting of other antigen targets in the future.",,"['Poosarla, Venkata Giridhar', 'Li, Tong', 'Goh, Boon Chong', 'Schulten, Klaus', 'Wood, Thomas K.', 'Maranas, Costas D.']",,,,
,PMC,L’outil « TOC »: Pour l’évaluation du risque chez vos patients fébriles ou atteints de maladie respiratoire aiguë en clinique de soins primaires,,PMC5395397,,,,,"['Trebuss, Kathryn', 'Horton, Jennifer', 'Gunanayagam, Angelo', 'MacDonald, Kyle', 'Moore, Kieran Michael']",,,,
,PMC,“TOC” to your patients: Risk assessment tool for patients with fever or acute respiratory illness in your primary care office,,PMC5395370,,,,,"['Trebuss, Kathryn', 'Horton, Jennifer', 'Gunanayagam, Angelo', 'MacDonald, Kyle', 'Moore, Kieran Michael']",,,,
,PMC,The Whys and Wherefores of Antibiotic Resistance,http://dx.doi.org/10.1101/cshperspect.a025171,PMC5287056,,,"The development and rapid dissemination of antibiotic-resistant bacterial pathogens has tarnished the dream of a world without infectious diseases. However, our understanding of these processes, paired with sequence information from terrestrial bacterial populations, indicates that there is no shortage of novel natural products that could be developed into new medicines. Regardless, their therapeutic success in the clinic will depend on the introduction of mandatory controls and use restrictions.",,"['Strachan, Cameron R.', 'Davies, Julian']",,,,
,PMC,"Measuring Global Disease with Wikipedia: Success, Failure, and a Research Agenda",http://dx.doi.org/10.1145/2998181.2998183,PMC5542563,,,"Effective disease monitoring provides a foundation for effective public health systems. This has historically been accomplished with patient contact and bureaucratic aggregation, which tends to be slow and expensive. Recent internet-based approaches promise to be real-time and cheap, with few parameters. However, the question of when and how these approaches work remains open. We addressed this question using Wikipedia access logs and category links. Our experiments, replicable and extensible using our open source code and data, test the effect of semantic article filtering, amount of training data, forecast horizon, and model staleness by comparing across 6 diseases and 4 countries using thousands of individual models. We found that our minimal-configuration, language-agnostic article selection process based on semantic relatedness is effective for improving predictions, and that our approach is relatively insensitive to the amount and age of training data. We also found, in contrast to prior work, very little forecasting value, and we argue that this is consistent with theoretical considerations about the nature of forecasting. These mixed results lead us to propose that the currently observational field of internet-based disease surveillance must pivot to include theoretical models of information flow as well as controlled experiments based on simulations of disease.",,"['Priedhorsky, Reid', 'Osthus, Dave', 'Daughton, Ashlynn R.', 'Moran, Kelly R.', 'Generous, Nicholas', 'Fairchild, Geoffrey', 'Deshpande, Alina', 'Del Valle, Sara Y.']",,,,
,PMC,Viral aetiology of wheezing in children under five,http://dx.doi.org/10.4103/ijmr.IJMR_840_15,PMC5501050,28639594,CC BY-NC-SA,"BACKGROUND & OBJECTIVES: Wheezing is a common problem in children under five with acute respiratory infections (ARIs). Viruses are known to be responsible for a considerable proportion of ARIs in children. This study was undertaken to know the viral aetiology of wheezing among the children less than five years of age, admitted to a tertiary care hospital in eastern India. METHODS: Seventy five children, under the age of five years admitted with wheezing, were included in the study. Throat and nasal swabs were collected, and real-time multiplex polymerase chain reaction (PCR) assay was used to screen for influenza 1 and 2, respiratory syncytial virus (RSV), parainfluenza virus (PIV) 1, 2, 3 and 4, rhinovirus, human meta-pneumovirus, bocavirus (HBoV), Coronavirus, adenovirus, Enterovirus and Parechovirus. RESULTS: The total viral detection rate was 28.57 per cent. Viral RNA markers were detected from children diagnosed to be having pneumonia (3 cases), bronchiolitis (9 cases), episodic wheeze (2 cases) and multitrigger wheeze (6 cases). RSV was the most common virus (35%) followed by PIV1, 2 and 3 (20%), HBoV (10%) and rhinovirus (5%). However, mixed infection was observed in 30 per cent of cases. INTERPRETATION & CONCLUSIONS: The study reported the presence of respiratory viral agents in 28.57 per cent of children with wheezing; RSV and PIV were most common, accounting to 55 per cent of the total cases. Mixed infection was reported in 30 per cent of cases. Seasonal variation in the occurrence of these viruses was also noted. Further studies need to be done with a large sample and longer follow up period to verify these findings.",2017 Feb,"['Mummidi, Prithi Sureka', 'Tripathy, Radha', 'Dwibedi, Bhagirathi', 'Mahapatra, Amarendra', 'Baraha, Suryakanta']",Indian J Med Res,,,
,PMC,Therapy with CTLA4-Ig and an antiviral monoclonal antibody controls chikungunya virus arthritis,http://dx.doi.org/10.1126/scitranslmed.aah3438,PMC5448557,,,"In 2013, chikungunya virus (CHIKV) transmission was documented in the Western Hemisphere, and the virus has since spread throughout the Americas with more than 1.8 million people infected in more than 40 countries. CHIKV targets the joints, resulting in symmetric polyarthritis that clinically mimics rheumatoid arthritis and can endure for months to years. At present, no approved treatment is effective in preventing or controlling CHIKV infection or disease. We treated mice with eight different disease-modifying antirheumatic drugs and identified CLTA4-Ig (abatacept) and tofacitinib as candidate therapies based on their ability to decrease acute joint swelling. CTLA4-Ig reduced T cell accumulation in the joints of infected animals without affecting viral infection. Whereas monotherapy with CTLA4-Ig or a neutralizing anti-CHIKV human monoclonal antibody provided partial clinical improvement, therapy with both abolished swelling and markedly reduced levels of chemokines, proinflammatory cytokines, and infiltrating leukocytes. Thus, combination CTLA4-Ig and antiviral antibody therapy controls acute CHIKV infection and arthritis and may be a candidate for testing in humans.",,"['Miner, Jonathan J.', 'Cook, Lindsey E.', 'Hong, Jun P.', 'Smith, Amber M.', 'Richner, Justin M.', 'Shimak, Raeann M.', 'Young, Alissa R.', 'Monte, Kristen', 'Poddar, Subhajit', 'Crowe, James E.', 'Lenschow, Deborah J.', 'Diamond, Michael S.']",,,,
,PMC,High Prevalence of Middle East Respiratory Coronavirus in Young Dromedary Camels in Jordan,http://dx.doi.org/10.1089/vbz.2016.2062,PMC5278817,,,Prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) was determined in 45 dromedary camels from two geographically separated herds in Jordan. Virus shedding was only detected in swabs obtained from the respiratory tract and primarily observed in camels younger than 3 years. MERS-CoV seroprevalence increased with age of camels. Bovine and sheep sera were seronegative. Phylogenetic analysis of partial S2 clustered the Jordanian MERS-CoV strains with contemporary MERS-CoV strains associated with nosocomial outbreaks.,,"['van Doremalen, Neeltje', 'Hijazeen, Zaidoun S.K.', 'Holloway, Peter', 'Al Omari, Bilal', 'McDowell, Chester', 'Adney, Danielle', 'Talafha, Hani A.', 'Guitian, Javier', 'Steel, John', 'Amarin, Nadim', 'Tibbo, Markos', 'Abu-Basha, Ehab', 'Al-Majali, Ahmad M.', 'Munster, Vincent J.', 'Richt, Juergen A.']",,,,
,PMC,ADP-ribosylhydrolase activity of Chikungunya virus macrodomain is critical for virus replication and virulence,http://dx.doi.org/10.1073/pnas.1621485114,PMC5321000,,,"Chikungunya virus (CHIKV), an Old World alphavirus, is transmitted to humans by infected mosquitoes and causes acute rash and arthritis, occasionally complicated by neurologic disease and chronic arthritis. One determinant of alphavirus virulence is nonstructural protein 3 (nsP3) that contains a highly conserved MacroD-type macrodomain at the N terminus, but the roles of nsP3 and the macrodomain in virulence have not been defined. Macrodomain is a conserved protein fold found in several plus-strand RNA viruses that binds to the small molecule ADP-ribose. Prototype MacroD-type macrodomains also hydrolyze derivative linkages on the distal ribose ring. Here, we demonstrated that the CHIKV nsP3 macrodomain is able to hydrolyze ADP-ribose groups from mono(ADP-ribosyl)ated proteins. Using mass spectrometry, we unambiguously defined its substrate specificity as mono(ADP-ribosyl)ated aspartate and glutamate but not lysine residues. Mutant viruses lacking hydrolase activity were unable to replicate in mammalian BHK-21 cells or mosquito Aedes albopictus cells and rapidly reverted catalytically inactivating mutations. Mutants with reduced enzymatic activity had slower replication in mammalian neuronal cells and reduced virulence in 2-day-old mice. Therefore, nsP3 mono(ADP-ribosyl)hydrolase activity is critical for CHIKV replication in both vertebrate hosts and insect vectors, and for virulence in mice.",,"['McPherson, Robert Lyle', 'Abraham, Rachy', 'Sreekumar, Easwaran', 'Ong, Shao-En', 'Cheng, Shang-Jung', 'Baxter, Victoria K.', 'Kistemaker, Hans A. V.', 'Filippov, Dmitri V.', 'Griffin, Diane E.', 'Leung, Anthony K. L.']",,,,
,PMC,An interaction domain in human SAMD9 is essential for myxoma virus host-range determinant M062 antagonism of host anti-viral function,http://dx.doi.org/10.1016/j.virol.2017.01.004,PMC5419587,,,"In humans, deleterious mutations in the sterile α motif domain protein 9 (SAMD9) gene are associated with cancer, inflammation, weakening of the immune response, and developmental arrest. However, the biological function of SAMD9 and its sequence-structure relationships remain to be characterized. Previously, we found that an essential host range factor, M062 protein from myxoma virus (MYXV), antagonizes the function of human SAMD9. In this study, we examine the interaction between M062 and human SAMD9 to identify regions that are critical to SAMD9 function. We also characterize the in vitro kinetics of the interaction. In an infection assay, exogenous expression of SAMD9 N-terminus leads to a potent inhibition of wild-type MYXV infection. We reason that this effect is due to the sequestration of viral M062 by the exogenously expressed N-terminal SAMD9 region. Our studies reveal the first molecular insight into viral M062-dependent mechanisms that suppress human SAMD9-associated antiviral function.",,"['Nounamo, Bernice', 'Li, Yibo', 'O’Byrne, Peter', 'Kearney, Aoife M.', 'Khan, Amir', 'Liu, Jia']",,,,
,PMC,"Stress hormones bring birds, pathogens and mosquitoes together",http://dx.doi.org/10.1016/j.pt.2017.01.001,PMC5410392,,,Do stress hormones such as corticosterone enhance bird susceptibility to mosquitoes in ways that enhance rates of coinfection? Does this then enhance pathogen emergence?,,"['Dhondt, André A.', 'Dobson, Andrew P.']",,,,
,PMC,"Impacts of different expressions of PA-X protein on 2009 pandemic H1N1 virus replication, pathogenicity and host immune responses",http://dx.doi.org/10.1016/j.virol.2017.01.015,PMC5651993,,,"Although several studies have investigated the functions of influenza PA-X, the impact of different expressions of PA-X protein including full-length, truncated or PA-X deficient forms on virus replication, pathogenicity and host response remains unclear. Herein, we generated two mutated viruses expressing a full-length or deficient PA-X protein based on the A/California/04/2009 (H1N1) virus that expresses a truncated PA-X to understand three different expressions of PA-X protein on virus replication, pathogenicity and host immune responses. The results showed that expression of either full-length or truncated PA-X protein enhanced viral replication and pathogenicity as well as reduced host innate immune response in mice by host shutoff activity when compared to the virus expressing the deficient PA-X form. Furthermore, the full-length PA-X expression exhibited a greater effect on virus pathogenicity than the truncated PA-X form. Our results provide novel insights of PA-X on viral replication, pathogenicity and host immune responses.",,"['Lee, Jinhwa', 'Yu, Hai', 'Li, Yonghai', 'Ma, Jingjiao', 'Lang, Yuekun', 'Duff, Michael', 'Henningson, Jamie', 'Liu, Qinfang', 'Li, Yuhao', 'Nagy, Abdou', 'Bawa, Bhupinder', 'Li, Zejun', 'Tong, Guangzhi', 'Richt, Juergen A.', 'Ma, Wenjun']",,,,
,PMC,Interferon-inducible LY6E Protein Promotes HIV-1 Infection,http://dx.doi.org/10.1074/jbc.M116.755819,PMC5377782,,,"LY6E is a glycosylphosphatidylinositol-anchored, IFN-inducible protein that regulates T lymphocytes proliferation, differentiation, and development. Single-nucleotide polymorphism rs2572886 in the LY6 family protein locus has been shown to associate with accelerated progression to AIDS. In this study, we show that LY6E promotes HIV, type 1 (HIV-1) infection by enhancing viral entry and gene expression. Knockdown of LY6E in human peripheral blood mononuclear, SupT1, and THP-1 cells diminishes HIV-1 replication. Virion-cell and cell-cell fusion experiments revealed that LY6E promotes membrane fusion of the viral entry step. Interestingly, we find that LTR-driven HIV-1 gene expression is also enhanced by LY6E, suggesting additional roles of LY6E in HIV-1 replication. HIV-1 infection induces LY6E expression in human peripheral blood mononuclear cells, concomitant with increased production of type I IFN and some classical IFN-stimulated genes. Altogether, our results demonstrate that IFN-inducible LY6E promotes HIV-1 entry and replication and highlight a positive regulatory role of IFN-induced proteins in HIV-1 infection. Our work emphasizes the complexity of IFN-mediated signaling in HIV-host interaction and AIDS pathogenesis.",,"['Yu, Jingyou', 'Liang, Chen', 'Liu, Shan-Lu']",,,,
,PMC,MPLEx: A method for simultaneous pathogen inactivation and extraction of samples for multi-omics profiling,http://dx.doi.org/10.1039/c6an02486f,PMC5283721,,,"The continued emergence and spread of infectious agents is of great concern, and systems biology approaches to infectious disease research can advance our understanding of host-pathogen relationships and facilitate the development of new therapies and vaccines. Molecular characterization of infectious samples outside of appropriate biosafety containment can take place only subsequent to pathogen inactivation. Herein, we describe a modified Folch extraction using chloroform/methanol that facilitates the molecular characterization of infectious samples by enabling simultaneous pathogen inactivation and extraction of proteins, metabolites, and lipids for subsequent mass spectrometry-based multi-omics measurements. This single-sample metabolite, protein and lipid extraction (MPLEx) method resulted in complete inactivation of clinically important bacterial and viral pathogens with exposed lipid membranes, including Yersinia pestis, Salmonella Typhimurium, and Campylobacter jejuni in pure culture, and Yersinia pestis, Campylobacter jejuni, and West Nile, MERS-CoV, Ebola, and influenza H7N9 viruses in infection studies. In addition, >99% inactivation, which increased with solvent exposure time, was also observed for pathogens without exposed lipid membranes including community-associated methicillin-resistant Staphylococcus aureus, Clostridium difficile spores and vegetative cells, and adenovirus type 5. The overall pipeline of inactivation and subsequent proteomic, metabolomic, and lipidomic analyses was evaluated using a human epithelial lung cell line infected with wild-type and mutant influenza H7N9 viruses, thereby demonstrating that MPLEx yields biomaterial of sufficient quality for subsequent multi-omics analyses. Based on these experimental results, we believe that MPLEx will facilitate systems biology studies of infectious samples by enabling simultaneous pathogen inactivation and multi-omics measurements from a single specimen with high success for pathogens with exposed lipid membranes.",,"['Burnum-Johnson, Kristin E.', 'Kyle, Jennifer E.', 'Eisfeld, Amie J.', 'Casey, Cameron P.', 'Stratton, Kelly G.', 'Gonzalez, Juan F.', 'Habyarimana, Fabien', 'Negretti, Nicholas M.', 'Sims, Amy C.', 'Chauhan, Sadhana', 'Thackray, Larissa B.', 'Halfmann, Peter J.', 'Walters, Kevin B.', 'Kim, Young-Mo', 'Zink, Erika M.', 'Nicora, Carrie D.', 'Weitz, Karl K.', 'Webb-Robertson, Bobbie-Jo M.', 'Nakayasu, Ernesto S.', 'Ahmer, Brian', 'Konkel, Michael E.', 'Motin, Vladimir', 'Baric, Ralph S.', 'Diamond, Michael S.', 'Kawaoka, Yoshihiro', 'Waters, Katrina M.', 'Smith, Richard D.', 'Metz, Thomas O.']",,,,
,PMC,Letter from the editor,http://dx.doi.org/10.1080/21645515.2017.1278976,PMC5287325,,,,,,,,,
,PMC,"Performance Evaluation of Allplex Respiratory Panels 1, 2, and 3 for Detection of Respiratory Viruses and Influenza A Virus Subtypes",http://dx.doi.org/10.1128/JCM.02045-16,PMC5277517,,,"The Allplex respiratory panels 1, 2, and 3 (Allplex) comprise a one-step real-time reverse transcription-PCR assay for the detection of respiratory viruses (RVs) and influenza A subtypes based on multiple detection temperature (MuDT) technology. The performance of the Allplex assay was compared with those of the AdvanSure RV real-time PCR kit (AdvanSure) and the PowerChek pandemic H1N1/H3N2/H5N1 real-time PCR kit (PowerChek) using 417 clinical respiratory specimens. In comparison with the AdvanSure assay for RV detection by each virus, the ranges of positive percent agreement, negative percent agreement, and kappa values with the Allplex assay were 82.8 to 100%, 95.5 to 100%, and 0.85 to 1.00, respectively. For influenza A virus (INF A) subtyping, the kappa values between the Allplex and PowerChek assays were 0.67 and 1.00 for the INF A H1N1-pdm09 and H3 subtypes, respectively. Uniplex PCR and sequencing for samples with discrepant results demonstrated that the majority of results were concordant with those from the Allplex assay. When testing 24 samples, the turnaround and hands-on time required to perform the Allplex assay were 4 h 15 min and 15 min, respectively. In conclusion, the Allplex assay produced results comparable to those from the AdvanSure and PowerChek assays.",,"['Huh, Hee Jae', 'Kim, Ji-Youn', 'Kwon, Hyeon Jeong', 'Yun, Sun Ae', 'Lee, Myoung-Keun', 'Lee, Nam Yong', 'Kim, Jong-Won', 'Ki, Chang-Seok']",,,,
,PMC,MicroRNA 155 and Viral-Induced Neuroinflammation,http://dx.doi.org/10.1016/j.jneuroim.2017.01.016,PMC5821228,,,"MicroRNA (miRNA) regulation of gene expression is becoming an increasingly recognized mechanism by which host immune responses are governed following microbial infection. miRNAs are short, non-coding RNAs that repress translation of target genes, and have been implicated in a number of activities that modulate host immune responses, including the regulation of immune cell proliferation, survival, expansion, differentiation, migration, polarization, and effector function. This review highlights several examples in which mammalian-encoded miR-155 influences immune responses following viral infection of the CNS.",,"['Dickey, Laura L.', 'Hanley, Timothy M.', 'Huffaker, Thomas B.', 'Ramstead, Andrew G.', 'O’Connell, Ryan M.', 'Lane, Thomas E.']",,,,
,PMC,Recent advances in the identification of the host factors involved in dengue virus replication,http://dx.doi.org/10.1007/s12250-016-3902-6,PMC6598876,,,"Dengue virus (DENV) belongs to the genus Flavivirus of the family Flaviviridae and it is primarily transmitted via Aedes aegypti and Aedes albopictus mosquitoes. The life cycle of DENV includes attachment, endocytosis, protein translation, RNA synthesis, assembly, egress, and maturation. Recent researches have indicated that a variety of host factors, including cellular proteins and microRNAs, positively or negatively regulate the DENV replication process. This review summarizes the latest findings (from 2014 to 2016) in the identification of the host factors involved in the DENV life cycle and Dengue infection.",,"['Wang, Yi', 'Zhang, Ping']",,,,
,PMC,BX-795 inhibits HSV-1 and HSV-2 replication by blocking the JNK/p38 pathways without interfering with PDK1 activity in host cells,http://dx.doi.org/10.1038/aps.2016.160,PMC5342671,,,"BX-795 is an inhibitor of 3-phosphoinositide-dependent kinase 1 (PDK1), but also a potent inhibitor of the IKK-related kinase, TANKbinding kinase 1 (TBK1) and IKKɛ. In this study we attempted to elucidate the molecular mechanism(s) underlying the inhibition of BX-795 on Herpes simplex virus (HSV) replication. HEC-1-A or Vero cells were treated with BX-795 and infected with HSV-1 or HSV-2 for different periods. BX-795 (3.125-25 μmol/L) dose-dependently suppressed HSV-2 replication, and displayed a low cytotoxicity to the host cells. BX-795 treatment dose-dependently suppressed the expression of two HSV immediate-early (IE) genes (ICP0 and ICP27) and the late gene (gD) at 12 h postinfection. HSV-2 infection resulted in the activation of PI3K and Akt in the host cells, and BX-795 treatment inhibited HSV-2-induced Akt phosphorylation and activation. However, the blockage of PI3K/Akt/mTOR with LY294002 and rapamycin did not affect HSV-2 replication. HSV-2 infection increased the phosphorylation of JNK and p38, and reduced ERK phosphorylation at 8 h postinfection in the host cells; BX-795 treatment inhibited HSV-2-induced activation of JNK and p38 MAP kinase as well as the phosphorylation of c-Jun and ATF-2, the downstream targets of JNK and p38 MAP kinase. Furthermore, SB203580 (a p38 inhibitor) or SP600125 (a JNK inhibitor) dose-dependently inhibited the viral replication in the host cells, whereas PD98059 (an ERK inhibitor) was not effective. Moreover, BX-795 blocked PMA-stimulated c-Jun activation as well as HSV-2-mediated c-Jun nuclear translocation. BX-795 dose-dependently inhibited HSV-2, PMA, TNF-α-stimulated AP-1 activation, but not HSV-induced NF-κB activation. Overexpression of p38/JNK attenuated the inhibitory effect of BX-795 on HSV replication. BX-795 completely blocked HSV-2-induced MKK4 phosphorylation, suggesting that BX-795 acting upstream of JNK and p38 MAP kinase. In conclusion, this study identifies the anti-HSV activity of BX-795 and its targeting of the JNK/p38 MAP kinase pathways in host cells.",,"['Su, Ai-rong', 'Qiu, Min', 'Li, Yan-lei', 'Xu, Wen-tao', 'Song, Si-wei', 'Wang, Xiao-hui', 'Song, Hong-yong', 'Zheng, Nan', 'Wu, Zhi-wei']",,,,
,PMC,Ro52 autoantibodies arise from self-reactive progenitors in a mother of a child with neonatal lupus,http://dx.doi.org/10.1016/j.jaut.2017.01.004,PMC5386791,,,"The detection of cardiac conduction defects in an 18-24 week old foetus in the absence of structural abnormalities predicts with near certainty the presence of autoantibodies against 60kD and 52kD SSA/Ro in the mother regardless of her health status. Previous studies have emphasized these autoantibodies as key mediators of tissue injury. The aim of this study was to focus on the anti-Ro52 response to determine whether these autoantibodies originate from progenitors that are inherently self-reactive or from B-cells that acquire self-reactivity during an immune response. We traced the evolution of two anti-Ro52 autoantibodies isolated from circulating IgG1-switched B-cells from an asymptomatic mother of a child with third degree congenital heart block. The autoantibodies were expressed as their immune form and as pre-immune ancestors by reverting somatic mutations to germline sequence. The reactivity of pre-immune and immune antibodies for Ro52, Ro60, La and DNA was measured. Both anti-Ro52 autoantibodies exhibited a low frequency of somatic mutations (3-4%) and utilised the same heavy and light chain genes but represented distinct clones based on differing complementarity determining region sequences. Pre- and post-immune antibodies showed specific binding to Ro52 with no measurable reactivity for other autoantigens. Ro52 binding was higher for immune antibodies compared to pre-immune counterparts demonstrating that autoreactivity was enhanced by affinity maturation. These data indicate that Ro52 reactivity is an intrinsic property of the germline antibody repertoire in a mother with a pathogenic antibody defined by cardiac injury in her offspring, and implies defects in both central and peripheral tolerance mechanisms.",,"['Reed, Joanne H.', 'Gorny, Miroslaw K.', 'Li, Liuzhe', 'Cardozo, Timothy', 'Buyon, Jill P.', 'Clancy, Robert M.']",,,,
,PMC,Soluble P-selectin rescues mice from anthrax lethal toxin-induced mortality through PSGL-1 pathway-mediated correction of hemostasis,http://dx.doi.org/10.1080/21505594.2017.1282027,PMC5711406,,,"As one of the virulence factors of Bacillus anthracis, lethal toxin (LT) induces various pathogenic responses including the suppression of the coagulation system. In this study, we observed that LT markedly increased the circulating soluble P-selectin (sP-sel) levels and microparticle (MP) count in wild-type but not P-selectin (P-sel, Selp(−/−)) or P-sel ligand-1 (PSGL-1, Selplg(−/−)) knockout mice. Because sP-sel induces a hypercoagulable state through PSGL-1 pathway to generate tissue factor-positive MPs, we hypothesized that the increase in plasma sP-sel levels can be a self-rescue response in hosts against the LT-mediated suppression of the coagulation system. In agreement with our hypothesis, our results indicated that compared with wild-type mice, Selp(−/−) and Selplg(−/−) mice were more sensitive to LT. In addition, the recombinant sP-sel treatment markedly ameliorated LT-mediated pathogenesis and reduced mortality. As a result, elicitation of circulating sP-sel is potentially a self-rescue response, which is beneficial to host recovery from an LT-induced hypocoagulation state. These results suggest that the administration of sP-sel is likely to be useful in the development of a new strategy to treat anthrax.",,"['Sun, Der-Shan', 'Chang, Yao-Wen', 'Kau, Jyh-Hwa', 'Huang, Hsin-Hsien', 'Ho, Pei-Hsun', 'Tzeng, Yin-Jeh', 'Chang, Hsin-Hou']",,,,
,PMC,Palmitoylation of Sindbis Virus TF Protein Regulates Its Plasma Membrane Localization and Subsequent Incorporation into Virions,http://dx.doi.org/10.1128/JVI.02000-16,PMC5244351,,,"Palmitoylation is a reversible, posttranslational modification that helps target proteins to cellular membranes. The alphavirus small membrane proteins 6K and TF have been reported to be palmitoylated and to positively regulate budding. 6K and TF are isoforms that are identical in their N termini but unique in their C termini due to a −1 ribosomal frameshift during translation. In this study, we used cysteine (Cys) mutants to test differential palmitoylation of the Sindbis virus 6K and TF proteins. We modularly mutated the five Cys residues in the identical N termini of 6K and TF, the four additional Cys residues in TF's unique C terminus, or all nine Cys residues in TF. Using these mutants, we determined that TF palmitoylation occurs primarily in the N terminus. In contrast, 6K is not palmitoylated, even on these shared residues. In the C-terminal Cys mutant, TF protein levels increase both in the cell and in the released virion compared to the wild type. In viruses with the N-terminal Cys residues mutated, TF is much less efficiently localized to the plasma membrane, and it is not incorporated into the virion. The three Cys mutants have minor defects in cell culture growth but a high incidence of abnormal particle morphologies compared to the wild-type virus as determined by transmission electron microscopy. We propose a model where the C terminus of TF modulates the palmitoylation of TF at the N terminus, and palmitoylated TF is preferentially trafficked to the plasma membrane for virus budding. IMPORTANCE Alphaviruses are a reemerging viral cause of arthritogenic disease. Recently, the small 6K and TF proteins of alphaviruses were shown to contribute to virulence in vivo. Nevertheless, a clear understanding of the molecular mechanisms by which either protein acts to promote virus infection is missing. The TF protein is a component of budded virions, and optimal levels of TF correlate positively with wild-type-like particle morphology. In this study, we show that the palmitoylation of TF regulates its localization to the plasma membrane, which is the site of alphavirus budding. Mutants in which TF is not palmitoylated display drastically reduced plasma membrane localization, which effectively prevents TF from participating in budding or being incorporated into virus particles. Investigation of the regulation of TF will aid current efforts in the alphavirus field searching for approaches to mitigate alphaviral disease in humans.",,"['Ramsey, Jolene', 'Renzi, Emily C.', 'Arnold, Randy J.', 'Trinidad, Jonathan C.', 'Mukhopadhyay, Suchetana']",,,,
,PMC,The Many Faces of the Flavivirus NS5 Protein in Antagonism of Type I Interferon Signaling,http://dx.doi.org/10.1128/JVI.01970-16,PMC5244349,,,"The vector-borne flaviviruses cause severe disease in humans on every inhabited continent on earth. Their transmission by arthropods, particularly mosquitoes, facilitates large emergence events such as witnessed with Zika virus (ZIKV) or West Nile virus in the Americas. Every vector-borne flavivirus examined thus far that causes disease in humans, from dengue virus to ZIKV, antagonizes the host type I interferon (IFN-I) response by preventing JAK-STAT signaling, suggesting that suppression of this pathway is an important determinant of infection. The most direct and potent viral inhibitor of this pathway is the nonstructural protein NS5. However, the mechanisms utilized by NS5 from different flaviviruses are often quite different, sometimes despite close evolutionary relationships between viruses. The varied mechanisms of NS5 as an IFN-I antagonist are also surprising given that the evolution of NS5 is restrained by the requirement to maintain function of two enzymatic activities critical for virus replication, the methyltransferase and RNA-dependent RNA polymerase. This review discusses the different strategies used by flavivirus NS5 to evade the antiviral effects of IFN-I and how this information can be used to better model disease and develop antiviral countermeasures.",,"Best, Sonja M.",,,,
,PMC,"Porcine Reproductive and Respiratory Syndrome Virus Antagonizes JAK/STAT3 Signaling via nsp5, Which Induces STAT3 Degradation",http://dx.doi.org/10.1128/JVI.02087-16,PMC5244345,,,"Signal transducer and activator of transcription 3 (STAT3) is a pleiotropic signaling mediator of many cytokines, including interleukin-6 (IL-6) and IL-10. STAT3 is known to play critical roles in cell growth, proliferation, differentiation, immunity and inflammatory responses. The objective of this study was to determine the effect of porcine reproductive and respiratory syndrome virus (PRRSV) infection on the STAT3 signaling since PRRSV induces a weak protective immune response in host animals. We report here that PRRSV infection of MARC-145 cells and primary porcine pulmonary alveolar macrophages led to significant reduction of STAT3 protein level. Several strains of both PRRSV type 1 and type 2 led to a similar reduction of STAT3 protein level but had a minimal effect on its transcripts. The PRRSV-mediated STAT3 reduction was in a dose-dependent manner as the STAT3 level decreased, along with incremental amounts of PRRSV inocula. Further study showed that nonstructural protein 5 (nsp5) of PRRSV induced the STAT3 degradation by increasing its polyubiquitination level and shortening its half-life from 24 h to ∼3.5 h. The C-terminal domain of nsp5 was shown to be required for the STAT3 degradation. Moreover, the STAT3 signaling in the cells transfected with nsp5 plasmid was significantly inhibited. These results indicate that PRRSV antagonizes the STAT3 signaling by accelerating STAT3 degradation via the ubiquitin-proteasomal pathway. This study provides insight into the PRRSV interference with the JAK/STAT3 signaling, leading to perturbation of the host innate and adaptive immune responses. IMPORTANCE The typical features of immune responses in PRRSV-infected pigs are delayed onset and low levels of virus neutralizing antibodies, as well as weak cell-mediated immunity. Lymphocyte development and differentiation rely on cytokines, many of which signal through the JAK/STAT signaling pathway to exert their biological effects. Here, we discovered that PRRSV antagonizes the JAK/STAT3 signaling by inducing degradation of STAT3, a master transcription activator involved in multiple cellular processes and the host immune responses. The nsp5 protein of PRRSV is responsible for the accelerated STAT3 degradation. The PRRSV-mediated antagonizing STAT3 could lead to suppression of a broad spectrum of cytokines and growth factors to allow virus replication and spread in host animals. This may be one of the reasons for the PRRSV interference with the innate immunity and its poor elicitation of protective immunity. This finding provides insight into PRRSV pathogenesis and its interference with the host immune responses.",,"['Yang, Liping', 'Wang, Rong', 'Ma, Zexu', 'Xiao, Yueqiang', 'Nan, Yuchen', 'Wang, Yu', 'Lin, Shaoli', 'Zhang, Yan-Jin']",,,,
,PMC,Ablation of Programmed −1 Ribosomal Frameshifting in Venezuelan Equine Encephalitis Virus Results in Attenuated Neuropathogenicity,http://dx.doi.org/10.1128/JVI.01766-16,PMC5244343,,,"The alphaviruses Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV) are arthropod-borne positive-strand RNA viruses that are capable of causing acute and fatal encephalitis in many mammals, including humans. VEEV was weaponized during the Cold War and is recognized as a select agent. Currently, there are no FDA-approved vaccines or therapeutics for these viruses. The spread of VEEV and other members of this family due to climate change-mediated vector range expansion underscores the need for research aimed at developing medical countermeasures. These viruses utilize programmed −1 ribosomal frameshifting (−1 PRF) to synthesize the viral trans-frame (TF) protein, which has previously been shown to be important for neuropathogenesis in the related Sindbis virus. Here, the alphavirus −1 PRF signals were characterized, revealing novel −1 PRF stimulatory structures. −1 PRF attenuation mildly affected the kinetics of VEEV accumulation in cultured cells but strongly inhibited its pathogenesis in an aerosol infection mouse model. Importantly, the decreased viral titers in the brains of mice infected with the mutant virus suggest that the alphavirus TF protein is important for passage through the blood-brain barrier and/or for neuroinvasiveness. These findings suggest a novel approach to the development of safe and effective live attenuated vaccines directed against VEEV and perhaps other closely related −1 PRF-utilizing viruses. IMPORTANCE Venezuelan equine encephalitis virus (VEEV) is a select agent that has been weaponized. This arthropod-borne positive-strand RNA virus causes acute and fatal encephalitis in many mammals, including humans. There is no vaccine or other approved therapeutic. VEEV and related alphaviruses utilize programmed −1 ribosomal frameshifting (−1 PRF) to synthesize the viral trans-frame (TF) protein, which is important for neuropathogenesis. −1 PRF attenuation strongly inhibited VEEV pathogenesis in mice, and viral replication analyses suggest that the TF protein is critical for neurological disease. These findings suggest a new approach to the development of safe and effective live attenuated vaccines directed against VEEV and other related viruses.",,"['Kendra, Joseph A.', 'de la Fuente, Cynthia', 'Brahms, Ashwini', 'Woodson, Caitlin', 'Bell, Todd M.', 'Chen, Bin', 'Khan, Yousuf A.', 'Jacobs, Jonathan L.', 'Kehn-Hall, Kylene', 'Dinman, Jonathan D.']",,,,
,PMC,Porcine Reproductive and Respiratory Syndrome Virus nsp1α Inhibits NF-κB Activation by Targeting the Linear Ubiquitin Chain Assembly Complex,http://dx.doi.org/10.1128/JVI.01911-16,PMC5244335,,,"Linear ubiquitination, a newly discovered posttranslational modification, is catalyzed by the linear ubiquitin chain assembly complex (LUBAC), which is composed of three subunits: one catalytic subunit HOIP and two accessory molecules, HOIL-1L and SHARPIN. Accumulating evidence suggests that linear ubiquitination plays a crucial role in innate immune signaling and especially in the activation of the NF-κB pathway by conjugating linear polyubiquitin chains to NF-κB essential modulator (NEMO, also called IKKγ), the regulatory subunit of the IKK complex. Porcine reproductive and respiratory syndrome virus (PRRSV), an Arterivirus that has devastated the swine industry worldwide, is an ideal model to study the host's disordered inflammatory responses after viral infection. Here, we found that LUBAC-induced NF-κB and proinflammatory cytokine expression can be inhibited in the early phase of PRRSV infection. Screening the PRRSV-encoded proteins showed that nonstructural protein 1α (nsp1α) suppresses LUBAC-mediated NF-κB activation and its CTE domain is required for the inhibition. Mechanistically, nsp1α binds to HOIP/HOIL-1L and impairs the interaction between HOIP and SHARPIN, thus reducing the LUBAC-dependent linear ubiquitination of NEMO. Moreover, PRRSV infection also blocks LUBAC complex formation and NEMO linear-ubiquitination, the important step for transducing NF-κB signaling. This unexpected finding demonstrates a previously unrecognized role of PRRSV nsp1α in modulating LUBAC signaling and explains an additional mechanism of immune modulation by PRRSV. IMPORTANCE Porcine reproductive and respiratory syndrome (PRRS) is one of the most important veterinary infectious diseases in countries with intensive swine industries. PRRS virus (PRRSV) infection usually suppresses proinflammatory cytokine expression in the early stage of infection, whereas it induces an inflammatory storm in the late stage. However, precisely how the virus is capable of doing so remains obscure. In this study, we found that by blocking the interaction of its catalytic subunit HOIP and accessory molecule SHARPIN, PRRSV can suppress NF-κB signal transduction in the early stage of infection. Our findings not only reveal a novel mechanism evolved by PRRSV to regulate inflammatory responses but also highlight the important role of linear ubiquitination modification during virus infection.",,"['Jing, Huiyuan', 'Fang, Liurong', 'Ding, Zhen', 'Wang, Dang', 'Hao, Wenqi', 'Gao, Li', 'Ke, Wenting', 'Chen, Huanchun', 'Xiao, Shaobo']",,,,
,PMC,Infectious Bursal Disease Virus Activates c-Src To Promote α4β1 Integrin-Dependent Viral Entry by Modulating the Downstream Akt-RhoA GTPase-Actin Rearrangement Cascade,http://dx.doi.org/10.1128/JVI.01891-16,PMC5244324,,,"While the entry of infectious bursal disease virus (IBDV) is initiated by the binding of the virus to the two major receptors integrin and HSP90, the signaling events after receptor binding and how they contribute to virus entry remain elusive. We show here that IBDV activates c-Src by inducing the phosphorylation of the Y416 residue in c-Src both in DF-1 chicken fibroblasts and in vivo in the bursa of Fabricius from specific-pathogen-free (SPF) chickens. Importantly, inactivated IBDV fails to stimulate c-Src Y416 phosphorylation, and a very virulent IBDV strain induces a much higher level of c-Src Y416 phosphorylation than does an attenuated strain. Inhibition of c-Src activation by an Src kinase inhibitor or expression of a c-Src dominant negative mutant results in a significant decrease in the internalization of IBDV but has little effect on virus adhesion. Furthermore, short hairpin RNA (shRNA) downregulation of integrin, either the α4 or β1 subunit, but not HSP90 remarkably attenuates IBDV-induced c-Src Y416 phosphorylation, resulting in a decrease in IBDV internalization but not virus adhesion. Moreover, interestingly, inhibition of either c-Src downstream of the phosphatidylinositol 3-kinase (PI3K)/Akt-RhoA signaling cascade or actin rearrangement leads to a significant decrease in IBDV internalization irrespective of the IBDV-induced high levels of c-Src phosphorylation. Cumulatively, our results suggest a novel feed-forward model whereby IBDV activates c-Src for benefiting its cell entry via an integrin-mediated pathway by the activation of downstream PI3K/Akt-RhoA signaling and cytoskeleton actin rearrangement. IMPORTANCE While IBDV-caused immunosuppression is highly related to viral invasion, the molecular basis of the cellular entry of IBDV remains elusive. In this study, we demonstrate that IBDV activates c-Src by inducing the phosphorylation of the Y416 residue in c-Src to promote virus internalization but not virus adhesion. The ability to induce the level of c-Src Y416 phosphorylation correlates with the pathogenicity of an IBDV strain. IBDV-induced c-Src Y416 activation is α4β1 integrin but not HSP90 dependent and involves the activation of the downstream PI3K/Akt-RhoA GTPase-actin rearrangement cascade. Thus, our findings provide new insights into the IBDV infection process and the potential for c-Src as a candidate target for the development of IBDV therapeutic drugs.",,"['Ye, Chengjin', 'Han, Xinpeng', 'Yu, Zhaoli', 'Zhang, Enli', 'Wang, Lijuan', 'Liu, Hebin']",,,,
,PMC,Hepatitis E virus ORF3 is a functional ion channel required for release of infectious particles,http://dx.doi.org/10.1073/pnas.1614955114,PMC5293053,,,"Hepatitis E virus (HEV) is the leading cause of enterically transmitted viral hepatitis globally. Of HEV’s three ORFs, the function of ORF3 has remained elusive. Here, we demonstrate that via homophilic interactions ORF3 forms multimeric complexes associated with intracellular endoplasmic reticulum (ER)-derived membranes. HEV ORF3 shares several structural features with class I viroporins, and the function of HEV ORF3 can be maintained by replacing it with the well-characterized viroporin influenza A virus (IAV) matrix-2 protein. ORF3’s ion channel function is further evidenced by its ability to mediate ionic currents when expressed in Xenopus laevis oocytes. Furthermore, we identified several positions in ORF3 critical for its formation of multimeric complexes, ion channel activity, and, ultimately, release of infectious particles. Collectively, our data demonstrate a previously undescribed function of HEV ORF3 as a viroporin, which may serve as an attractive target in developing direct-acting antivirals.",,"['Ding, Qiang', 'Heller, Brigitte', 'Capuccino, Juan M. V.', 'Song, Bokai', 'Nimgaonkar, Ila', 'Hrebikova, Gabriela', 'Contreras, Jorge E.', 'Ploss, Alexander']",,,,
,PMC,A Simple Red Blood Cell Lysis Method for the Establishment of B Lymphoblastoid Cell Lines,http://dx.doi.org/10.3791/55191,PMC5352257,,,"A number of methods exist for the transformation of B lymphocytes by the Epstein Barr virus in vitro into immortalized cell lines. We have developed a new method with a powerful and simple strategy for the establishment of B-LCLs, the red blood cell lysis method. This method simplified the PBMC separation procedure with red blood cell removal, and used as little as 0.5 mL of whole blood for establishing EBV-immortalized cell lines, which can proliferate to large cell numbers in a relatively short amount time with a 100% success rate. The method is simple, reliable, time saving, and applicable to treating a large number of the clinical samples.",,"['Liu, Xi', 'Xu, Chongfeng', 'Duan, Ziyuan']",,,,
,PMC,A Human Proteome Array Approach to Identifying Key Host Proteins Targeted by Toxoplasma Kinase ROP18,http://dx.doi.org/10.1074/mcp.M116.063602,PMC5341007,,,"Toxoplasma kinase ROP18 is a key molecule responsible for the virulence of Toxoplasma gondii; however, the mechanisms by which ROP18 exerts parasite virulence via interaction with host proteins remain limited to a small number of identified substrates. To identify a broader array of ROP18 substrates, we successfully purified bioactive mature ROP18 and used it to probe a human proteome array. Sixty eight new putative host targets were identified. Functional annotation analysis suggested that these proteins have a variety of functions, including metabolic process, kinase activity and phosphorylation, cell growth, apoptosis and cell death, and immunity, indicating a pleiotropic role of ROP18 kinase. Among these proteins, four candidates, p53, p38, UBE2N, and Smad1, were further validated. We demonstrated that ROP18 targets p53, p38, UBE2N, and Smad1 for degradation. Importantly, we demonstrated that ROP18 phosphorylates Smad1 Ser-187 to trigger its proteasome-dependent degradation. Further functional characterization of the substrates of ROP18 may enhance understanding of the pathogenesis of Toxoplasma infection and provide new therapeutic targets. Similar strategies could be used to identify novel host targets for other microbial kinases functioning at the pathogen-host interface.",,"['Yang, Zhaoshou', 'Hou, Yongheng', 'Hao, Taofang', 'Rho, Hee-Sool', 'Wan, Jun', 'Luan, Yizhao', 'Gao, Xin', 'Yao, Jianping', 'Pan, Aihua', 'Xie, Zhi', 'Qian, Jiang', 'Liao, Wanqin', 'Zhu, Heng', 'Zhou, Xingwang']",,,,
,PMC,A single MIU motif of MINDY‐1 recognizes K48‐linked polyubiquitin chains,http://dx.doi.org/10.15252/embr.201643205,PMC5331195,,,The eight different types of ubiquitin (Ub) chains that can be formed play important roles in diverse cellular processes. Linkage‐selective recognition of Ub chains by Ub‐binding domain (UBD)‐containing proteins is central to coupling different Ub signals to specific cellular responses. The motif interacting with ubiquitin (MIU) is a small UBD that has been characterized for its binding to monoUb. The recently discovered deubiquitinase MINDY‐1/FAM63A contains a tandem MIU repeat (tMIU) that is highly selective at binding to K48‐linked polyUb. We here identify that this linkage‐selective binding is mediated by a single MIU motif (MIU2) in MINDY‐1. The crystal structure of MIU2 in complex with K48‐linked polyubiquitin chains reveals that MIU2 on its own binds to all three Ub moieties in an open conformation that can only be accommodated by K48‐linked triUb. The weak Ub binder MIU1 increases overall affinity of the tMIU for polyUb chains without affecting its linkage selectivity. Our analyses reveal new concepts for linkage selectivity and polyUb recognition by UBDs.,,"['Kristariyanto, Yosua Adi', 'Abdul Rehman, Syed Arif', 'Weidlich, Simone', 'Knebel, Axel', 'Kulathu, Yogesh']",,,,
,PMC,Isolation of Coronavirus NL63 from Blood from Children in Rural Haiti: Phylogenetic Similarities with Recent Isolates from Malaysia,http://dx.doi.org/10.4269/ajtmh.16-0585,PMC5239682,,,"Human coronavirus (HCoV) NL63 is recognized as a common cause of upper respiratory infections and influenza-like illness. In screening children with acute undifferentiated febrile illness in a school cohort in rural Haiti, we identified HCoV-NL63 in blood samples from four children. Cases clustered over an 11-day period; children did not have respiratory symptoms, but two had gastrointestinal complaints. On phylogenetic analysis, the Haitian HCoV-NL63 strains cluster together in a highly supported monophyletic clade linked most closely with recently reported strains from Malaysia; two respiratory HCoV-NL63 strains identified in north Florida in the same general period form a separate clade, albeit again with close linkages with the Malaysian strains. Our data highlight the variety of presentations that may be seen with HCoV-NL63, and underscore the apparent ease with which CoV strains move among countries, with our data consistent with recurrent introduction of strains into the Caribbean (Haiti and Florida) from Asia.",,"['Beau De Rochars, Valery Madsen', 'Lednicky, John', 'White, Sarah', 'Loeb, Julia', 'Elbadry, Maha A.', 'Telisma, Taina', 'Chavannes, Sonese', 'Anilis, Marie Gina', 'Cella, Eleonora', 'Ciccozzi, Massimo', 'Okech, Bernard A.', 'Salemi, Marco', 'Morris, J. Glenn']",,,,
,PMC,Immunobiology of Long Noncoding RNAs,http://dx.doi.org/10.1146/annurev-immunol-041015-055459,PMC6449690,,,"The discovery of long noncoding RNAs (lncRNA) has provided a new perspective on gene regulation in diverse biological contexts. lncRNAs are remarkably versatile molecules that interact with RNA, DNA or proteins to promote or restrain expression of protein-coding genes. Activation of immune cells is associated with dynamic changes in gene expression, the products of which combat infectious microorganisms, initiate repair and resolve inflammatory responses in cells and tissues. Recent evidence indicates that lncRNAs play important roles in directing the development of diverse immune cells and controlling the dynamic transcriptional programs that are a hallmark of immune cell activation. The importance of these molecules is underscored by their newly recognized roles in inflammatory diseases. In this review, we discuss the contribution of lncRNAs to immune cell lineage development, immune cell activation and immune related diseases. We also discuss the challenges faced in identifying biological functions for this large and complex class of genes.",,"['Atianand, Maninjay K.', 'Caffrey, Daniel R.', 'Fitzgerald, Katherine A.']",,,,
,PMC,Viral-induced suppression of self-reactive T cells: Lessons from neurotropic coronavirus-induced demyelination,http://dx.doi.org/10.1016/j.jneuroim.2017.01.003,PMC5474352,,,"Genetic and environmental factors, i.e. infections, have been proposed to contribute to disease induction and relapsing events in multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system (CNS). While research has mainly focused on virus associated autoimmune activation, less is known about prevention of autoimmunity, especially following resolving infections associated with CNS tissue damage. This review discusses novel insights on control of self-reactive (SR) T cells activated during neurotropic coronavirus-induced demyelination. A new concept is introduced that SR T cells can be dampened by distinct regulatory mechanisms in the periphery and the CNS, thereby preventing autoimmune disease.",,"['Savarin, Carine', 'Bergmann, Cornelia C.']",,,,
,PMC,The SRL peptide of Rhesus Rotavirus VP4 protein governs cholangiocyte infection and the murine model of biliary atresia,http://dx.doi.org/10.1002/hep.28947,PMC5360466,,,"Biliary atresia (BA) is a neonatal obstructive cholangiopathy which progresses to end stage liver disease, often requiring transplantation. The murine model of BA, employing rhesus rotavirus (RRV), parallels human disease and has been used to elucidate mechanistic aspects of a virus induced biliary cholangiopathy. We previously reported that RRV VP4 gene plays an integral role in activating the immune system and induction of BA. Utilizing rotavirus binding and blocking assays, this study elucidated how RRV VP4 protein governs cholangiocyte susceptibility to infection both in vitro and in vivo in the murine model of BA. We identified the amino acid sequence on VP4 and its cholangiocyte binding protein, finding that the sequence is specific to those rotavirus strains which cause an obstructive cholangiopathy. Pretreatment of murine and human cholangiocytes with this VP4 derived peptide (TRTRVSRLY), significantly reduced RRV’s ability to bind and infect the cells. However, the peptide did not block cholangiocyte binding of TUCH and Ro1845, strains which do not induce murine BA. The SRL sequence within TRTRVSRLY is required for cholangiocyte binding and viral replication. The cholangiocyte membrane protein bound by SRL was found to be Hsc70. Inhibition of Hsc70 by siRNAs reduced RRV’s ability to infect cholangiocytes. This virus-cholangiocyte interaction is also seen in vivo in the murine model of BA, where inoculation of mice with TRTRVSRLY peptide significantly reduced symptoms and mortality in RRV-injected mice. CONCLUSION: The tri-peptide SRL on RRV VP4 binds to the cholangiocyte membrane protein Hsc70 defining a novel binding site governing VP4 attachment. Investigations are underway to determine the cellular response following this interaction to understand how it contributes to the pathogenesis of BA.",,"['Mohanty, Sujit K.', 'Donnelly, Bryan', 'Lobeck, Inna', 'Walther, Ashley', 'Dupree, Phylicia', 'Coots, Abigail', 'Meller, Jaroslaw', 'McNeal, Monica', 'Sestak, Karol', 'Tiao, Greg']",,,,
,PMC,Plasma membrane wounding and repair in pulmonary diseases,http://dx.doi.org/10.1152/ajplung.00486.2016,PMC5374305,,,"Various pathophysiological conditions such as surfactant dysfunction, mechanical ventilation, inflammation, pathogen products, environmental exposures, and gastric acid aspiration stress lung cells, and the compromise of plasma membranes occurs as a result. The mechanisms necessary for cells to repair plasma membrane defects have been extensively investigated in the last two decades, and some of these key repair mechanisms are also shown to occur following lung cell injury. Because it was theorized that lung wounding and repair are involved in the pathogenesis of acute respiratory distress syndrome (ARDS) and idiopathic pulmonary fibrosis (IPF), in this review, we summarized the experimental evidence of lung cell injury in these two devastating syndromes and discuss relevant genetic, physical, and biological injury mechanisms, as well as mechanisms used by lung cells for cell survival and membrane repair. Finally, we discuss relevant signaling pathways that may be activated by chronic or repeated lung cell injury as an extension of our cell injury and repair focus in this review. We hope that a holistic view of injurious stimuli relevant for ARDS and IPF could lead to updated experimental models. In addition, parallel discussion of membrane repair mechanisms in lung cells and injury-activated signaling pathways would encourage research to bridge gaps in current knowledge. Indeed, deep understanding of lung cell wounding and repair, and discovery of relevant repair moieties for lung cells, should inspire the development of new therapies that are likely preventive and broadly effective for targeting injurious pulmonary diseases.",,"['Cong, Xiaofei', 'Hubmayr, Rolf D.', 'Li, Changgong', 'Zhao, Xiaoli']",,,,
,PMC,A novel view of the adult stem cell compartment from the perspective of a quiescent population of very small embryonic-like stem cells,http://dx.doi.org/10.1161/CIRCRESAHA.116.309362,PMC5221475,,,"Evidence has accumulated that adult hematopoietic tissues and other organs contain a population of dormant stem cells (SCs) that are more primitive than other, already restricted, monopotent tissue-committed stem cells (TCSCs). These observations raise several questions, such as the developmental origin of these cells, their true pluripotent or multipotent nature, which surface markers they express, how they can be efficiently isolated from adult tissues, and what role they play in the adult organism. The phenotype of these cells and expression of some genes characteristic of embryonic SCs (ESCs), epiblast SCs (EPiSCs), and primordial germ cells (PGCs) suggests their early-embryonic deposition in developing tissues as precursors of adult SCs. In this review we will critically discuss all these questions and the concept that small dormant stem cells related to migratory PGCs, described as very small embryonic-like stem cells (VSELs), are deposited during embryogenesis in bone marrow and other organs as a backup population for adult tissue committed stem cells (TCSCs) and are involved in several processes related to tissue or organ rejuvenation, aging, and cancerogenesis. The most recent results on successful ex vivo expansion of human VSELs in chemically defined media free from feeder-layer cells opens up new and exciting possibilities for their application in regenerative medicine.",,"['Ratajczak, Mariusz Z.', 'Ratajczak, Janina', 'Suszynska, Malwina', 'Miller, Donald M.', 'Kucia, Magda', 'Shin, Dong-Myung']",,,,
,PMC,Simultaneous Intranasal/Intravascular Antibody Labeling of CD4(+) T Cells in Mouse Lungs,http://dx.doi.org/10.21769/BioProtoc.2099,PMC5431592,,,"CD4(+) T cell responses have been shown to be protective in many respiratory virus infections. In the respiratory tract, CD4(+) T cells include cells in the airway and parenchyma and cells adhering to the pulmonary vasculature. Here we discuss in detail the methods that are useful for characterizing CD4(+) T cells in different anatomic locations in mouse lungs.",,"['Wang, Yanqun', 'Sun, Jing', 'Channappanavar, Rudragouda', 'Zhao, Jingxian', 'Perlman, Stanley', 'Zhao, Jincun']",,,,
,PMC,Multivalent and Multipathogen Viral Vector Vaccines,http://dx.doi.org/10.1128/CVI.00298-16,PMC5216423,,,"The presentation and delivery of antigens are crucial for inducing immunity and, desirably, lifelong protection. Recombinant viral vectors—proven safe and successful in veterinary vaccine applications—are ideal shuttles to deliver foreign proteins to induce an immune response with protective antibody levels by mimicking natural infection. Some examples of viral vectors are adenoviruses, measles virus, or poxviruses. The required attributes to qualify as a vaccine vector are as follows: stable insertion of coding sequences into the genome, induction of a protective immune response, a proven safety record, and the potential for large-scale production. The need to develop new vaccines for infectious diseases, increase vaccine accessibility, reduce health costs, and simplify overloaded immunization schedules has driven the idea to combine antigens from the same or various pathogens. To protect effectively, some vaccines require multiple antigens of one pathogen or different pathogen serotypes/serogroups in combination (multivalent or polyvalent vaccines). Future multivalent vaccine candidates are likely to be required for complex diseases like malaria and HIV. Other novel strategies propose an antigen combination of different pathogens to protect against several diseases at once (multidisease or multipathogen vaccines).",,"['Lauer, Katharina B.', 'Borrow, Ray', 'Blanchard, Thomas J.']",,,,
,PMC,PERK and XBP1 differentially regulate CXCL10 and CCL2 production,http://dx.doi.org/10.1016/j.exer.2017.01.002,PMC5359061,,,"Inflammation plays a key role in the pathogenesis of many retinal degenerative diseases related with photoreceptor dysfunction/degeneration. However the involvement of photoreceptor cells in inflammatory reactions is largely unknown as they are not considered as inflammatory cells. In this study, we assessed whether photoreceptor cells can produce CCL2 and CXCL10, two important players in inflammation during endoplasmic reticulum (ER) stress. After photoreceptor 661W cells were treated with ER stress inducer thapsigargin (TG), induction of ER stress increased CXCL10 and CCL2 expression at both mRNA and protein levels, which was significantly blocked by an ER stress blocker 4-phenylbutyrate. ER stress contains three pathways: PERK, ATF6 and IRE1α. Knockdown of PERK attenuated TG-induced CXCL10 and CCL2 mRNA expression, associated with significant decreases in phosphorylation of NF-κB RelA and STAT3. In contrast to PERK, knockdown of XBP1, which is activated by IRE1α-mediated splicing, robustly enhanced TG-induced CXCL10 and CCL2 expression and phosphorylation of NF-κB RelA and STAT3. Blockade of NF-κB or STAT3 markedly diminished TG-induced CXCL10 and CCL2 expression. The specific roles of PERK and XBP1 in CXCL10 and CCL2 expression were further investigated by treating photoreceptor cells with advanced glycation end products (AGE) and high glucose (HG), two of the major contributors to diabetic complications. Similarly, AGE and HG induced CXCL10 and CCL2 expression in which PERK was a positive regulator while XBP1 was a negative regulator. These studies suggest that photoreceptors may be involved in retinal inflammation by expressing chemokines CXCL10 and CCL2. PERK and IRE1α/XBP1 in the unfolded protein response differentially regulate the expression of CXCL10 and CCL2 likely through modulation of ER stress-induced NF-κB RelA and STAT3 activation.",,"['Zhu, Shuang', 'Liu, Hua', 'Sha, Haibo', 'Qi, Ling', 'Gao, Dian-shuai', 'Zhang, Wenbo']",,,,
,PMC,IgG Fc variant cross-reactivity between human and rhesus macaque FcγRs,http://dx.doi.org/10.1080/19420862.2016.1274845,PMC5384711,,,"Non-human primate (NHP) studies are often an essential component of antibody development efforts before human trials. Because the efficacy or toxicity of candidate antibodies may depend on their interactions with Fcγ receptors (FcγR) and their resulting ability to induce FcγR-mediated effector functions such as antibody-dependent cell-meditated cytotoxicity and phagocytosis (ADCP), the evaluation of human IgG variants with modulated affinity toward human FcγR is becoming more prevalent in both infectious disease and oncology studies in NHP. Reliable translation of these results necessitates analysis of the cross-reactivity of these human Fc variants with NHP FcγR. We report evaluation of the binding affinities of a panel of human IgG subclasses, Fc amino acid point mutants and Fc glycosylation variants against the common allotypes of human and rhesus macaque FcγR by applying a high-throughput array-based surface plasmon resonance platform. The resulting data indicate that amino acid variation present in rhesus FcγRs can result in disrupted, matched, or even increased affinity of IgG Fc variants compared with human FcγR orthologs. These observations emphasize the importance of evaluating species cross-reactivity and developing an understanding of the potential limitations or suitability of representative in vitro and in vivo models before human clinical studies when either efficacy or toxicity may be associated with FcγR engagement.",,"['Boesch, Austin W.', 'Miles, Adam R.', 'Chan, Ying N.', 'Osei-Owusu, Nana Y.', 'Ackerman, Margaret E.']",,,,
,PMC,Roles of regulatory T cells and IL-10 in virus-induced demyelination,http://dx.doi.org/10.1016/j.jneuroim.2017.01.001,PMC5474348,,,"Neurotropic viruses are important causes of morbidity and mortality in human populations. Some of these viruses preferentially infect oligodendrocytes in the white matter, causing either direct lysis of infected cells, or more commonly myelin damage as a consequence of the host immune response to the virus. Virus-induced demyelination has similarities to the human disease multiple sclerosis. To study this disease process in experimental animals, mice are infected, most commonly, with neurotropic strains of mouse hepatitis virus, a coronavirus or Theiler’s murine encephalomyelitis, a picornavirus. While the diseases caused by these two viruses differ in some aspects, in both cases demyelination is a major consequence of the infection. As in autoimmune disease, therapeutic interventions that diminish an overactive immune response would be useful. However, unlike autoimmune disease, complete suppression would result in unchecked virus replication, generally leading to more severe disease. Here we discuss two approaches that dampen but do not fully suppress the host immune response. Regulatory T cells, especially those that are specific for antigens recognized by pathogenic T cells, and IL-10 are two anti-inflammatory/pro-resolution factors that demonstrate efficacy in experimental models of virus-induced demyelination and may be useful in patients infected with viruses that cause demyelination.",,"['Perlman, Stanley', 'Zhao, Jingxian']",,,,
,PMC,"One-Health: a Safe, Efficient, Dual-Use Vaccine for Humans and Animals against Middle East Respiratory Syndrome Coronavirus and Rabies Virus",http://dx.doi.org/10.1128/JVI.02040-16,PMC5215356,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and is a highly pathogenic respiratory virus. There are no treatment options against MERS-CoV for humans or animals, and there are no large-scale clinical trials for therapies against MERS-CoV. To address this need, we developed an inactivated rabies virus (RABV) that contains the MERS-CoV spike (S) protein expressed on its surface. Our initial recombinant vaccine, BNSP333-S, expresses a full-length wild-type MERS-CoV S protein; however, it showed significantly reduced viral titers compared to those of the parental RABV strain and only low-level incorporation of full-length MERS-CoV S into RABV particles. Therefore, we developed a RABV-MERS vector that contained the MERS-CoV S1 domain of the MERS-CoV S protein fused to the RABV G protein C terminus (BNSP333-S1). BNSP333-S1 grew to titers similar to those of the parental vaccine vector BNSP333, and the RABV G–MERS-CoV S1 fusion protein was efficiently expressed and incorporated into RABV particles. When we vaccinated mice, chemically inactivated BNSP333-S1 induced high-titer neutralizing antibodies. Next, we challenged both vaccinated mice and control mice with MERS-CoV after adenovirus transduction of the human dipeptidyl peptidase 4 (hDPP4) receptor and then analyzed the ability of mice to control MERS-CoV infection. Our results demonstrated that vaccinated mice were fully protected from the MERS-CoV challenge, as indicated by the significantly lower MERS-CoV titers and MERS-CoV and mRNA levels in challenged mice than those in unvaccinated controls. These data establish that an inactivated RABV-MERS S-based vaccine may be effective for use in animals and humans in areas where MERS-CoV is endemic. IMPORTANCE Rabies virus-based vectors have been proven to be efficient dual vaccines against rabies and emergent infectious diseases such as Ebola virus. Here we show that inactivated rabies virus particles containing the MERS-CoV S1 protein induce potent immune responses against MERS-CoV and RABV. This novel vaccine is easy to produce and may be useful to protect target animals, such as camels, as well as humans from deadly MERS-CoV and RABV infections. Our results indicate that this vaccine approach can prevent disease, and the RABV-based vaccine platform may be a valuable tool for timely vaccine development against emerging infectious diseases.",,"['Wirblich, Christoph', 'Coleman, Christopher M.', 'Kurup, Drishya', 'Abraham, Tara S.', 'Bernbaum, John G.', 'Jahrling, Peter B.', 'Hensley, Lisa E.', 'Johnson, Reed F.', 'Frieman, Matthew B.', 'Schnell, Matthias J.']",,,,
,PMC,Structure of a Human Astrovirus Capsid-Antibody Complex and Mechanistic Insights into Virus Neutralization,http://dx.doi.org/10.1128/JVI.01859-16,PMC5215351,,,"Human astroviruses (HAstVs) are a leading cause of viral diarrhea in young children, the immunocompromised, and the elderly. There are no vaccines or antiviral therapies against HAstV disease. Several lines of evidence point to the presence of protective antibodies in healthy adults as a mechanism governing protection against reinfection by HAstV. However, development of anti-HAstV therapies is hampered by the gap in knowledge of protective antibody epitopes on the HAstV capsid surface. Here, we report the structure of the HAstV capsid spike domain bound to the neutralizing monoclonal antibody PL-2. The antibody uses all six complementarity-determining regions to bind to a quaternary epitope on each side of the dimeric capsid spike. We provide evidence that the HAstV capsid spike is a receptor-binding domain and that the antibody neutralizes HAstV by blocking virus attachment to cells. We identify patches of conserved amino acids that overlap the antibody epitope and may comprise a receptor-binding site. Our studies provide a foundation for the development of therapies to prevent and treat HAstV diarrheal disease. IMPORTANCE Human astroviruses (HAstVs) infect nearly every person in the world during childhood and cause diarrhea, vomiting, and fever. Despite the prevalence of this virus, little is known about how antibodies in healthy adults protect them against reinfection. Here, we determined the crystal structure of a complex of the HAstV capsid protein and a virus-neutralizing antibody. We show that the antibody binds to the outermost spike domain of the capsid, and we provide evidence that the antibody blocks virus attachment to human cells. Importantly, our findings suggest that a subunit-based vaccine focusing the immune system on the HAstV capsid spike domain could be effective in protecting children against HAstV disease.",,"['Bogdanoff, Walter A.', 'Campos, Jocelyn', 'Perez, Edmundo I.', 'Yin, Lu', 'Alexander, David L.', 'DuBois, Rebecca M.']",,,,
,PMC,Porcine Epidemic Diarrhea Virus 3C-Like Protease-Mediated Nucleocapsid Processing: Possible Link to Viral Cell Culture Adaptability,http://dx.doi.org/10.1128/JVI.01660-16,PMC5215342,,,"Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and high mortality rates in newborn piglets, leading to massive losses to the swine industry worldwide during recent epidemics. Intense research efforts are now focusing on defining viral characteristics that confer a growth advantage, pathogenicity, or cell adaptability in order to better understand the PEDV life cycle and identify suitable targets for antiviral or vaccine development. Here, we report a unique phenomenon of PEDV nucleocapsid (N) cleavage by the PEDV-encoded 3C-like protease (3Cpro) during infection. The identification of the 3Cpro cleavage site at the C terminus of N supported previous observations that PEDV 3Cpro showed a substrate requirement slightly different from that of severe acute respiratory syndrome coronavirus (SARS-CoV) 3Cpro and revealed a greater flexibility in its substrate recognition site. This cleavage motif is present in the majority of cell culture-adapted PEDV strains but is missing in emerging field isolates. Remarkably, reverse-genetics-derived cell culture-adapted PEDV(AVCT12) harboring uncleavable N displayed growth retardation in Vero E6-APN cells compared to the wild-type virus. These observations altogether shed new light on the investigation and characterization of the PEDV nucleocapsid protein and its possible link to cell culture adaptation. IMPORTANCE Recurrent PEDV outbreaks have resulted in enormous economic losses to swine industries worldwide. To gain the upper hand in combating this disease, it is necessary to understand how this virus replicates and evades host immunity. Characterization of viral proteins provides important clues to mechanisms by which viruses survive and spread. Here, we characterized an intriguing phenomenon in which the nucleocapsids of some PEDV strains are proteolytically processed by the virally encoded main protease. Growth retardation in recombinant PEDV carrying uncleavable N suggests a replication advantage provided by the cleavage event, at least in the cell culture system. These findings may direct us to a more complete understanding of PEDV replication and pathogenicity.",,"['Jaru-Ampornpan, Peera', 'Jengarn, Juggragarn', 'Wanitchang, Asawin', 'Jongkaewwattana, Anan']",,,,
,PMC,Evolution and Cryo-electron Microscopy Capsid Structure of a North American Bat Adenovirus and Its Relationship to Other Mastadenoviruses,http://dx.doi.org/10.1128/JVI.01504-16,PMC5215340,,,"Since the first description of adenoviruses in bats in 2006, a number of micro- and megabat species in Europe, Africa, and Asia have been shown to carry a wide diversity of adenoviruses. Here, we report on the evolutionary, biological, and structural characterization of a novel bat adenovirus (BtAdV) recovered from a Rafinesque's big-eared bat (Corynorhinus rafinesquii) in Kentucky, USA, which is the first adenovirus isolated from North American bats. This virus (BtAdV 250-A) exhibits a close phylogenetic relationship with Canine mastadenovirus A (CAdV A), as previously observed with other BtAdVs. To further investigate the relationships between BtAdVs and CAdVs, we conducted mass spectrometric analysis and single-particle cryo-electron microscopy reconstructions of the BtAdV 250-A capsid and also analyzed the in vitro host ranges of both viruses. Our results demonstrate that BtAdV 250-A represents a new mastadenovirus species that, in contrast to CAdV, has a unique capsid morphology that contains more prominent extensions of protein IX and can replicate efficiently in a phylogenetically diverse range of species. These findings, in addition to the recognition that both the genetic diversity of BtAdVs and the number of different bat species from disparate geographic regions infected with BtAdVs appears to be extensive, tentatively suggest that bats may have served as a potential reservoir for the cross-species transfer of adenoviruses to other hosts, as theorized for CAdV. IMPORTANCE Although many adenoviruses are host specific and likely codiverged with their hosts over millions of years, other adenoviruses appear to have emerged through successful cross-species transmission events on more recent time scales. The wide geographic distribution and genetic diversity of adenoviruses in bats and their close phylogenetic relationship to Canine mastadenovirus A (CAdV A) has raised important questions about how CAdV A, and possibly other mammalian adenoviruses, may have emerged. Although most adenoviruses tend to cause limited disease in their natural hosts, CAdV A is unusual in that it may cause high morbidity and sometimes fatal infections in immunocompetent hosts and is thus an important pathogen of carnivores. Here, we performed a comparative evolutionary and structural study of representative bat and canine adenoviruses to better understand the relationship between these two viral groups.",,"['Hackenbrack, Nicole', 'Rogers, Matthew B.', 'Ashley, Robert E.', 'Keel, M. Kevin', 'Kubiski, Steven V.', 'Bryan, John A.', 'Ghedin, Elodie', 'Holmes, Edward C.', 'Hafenstein, Susan L.', 'Allison, Andrew B.']",,,,
,PMC,A Consequential Eight Years for Health Care and Public Health,http://dx.doi.org/10.2105/AJPH.2016.303538,PMC5308178,,,,,"McDonough, John E.",,,,
,PMC,Filovirus Strategies to Escape Antiviral Responses,http://dx.doi.org/10.1007/82_2017_13,PMC5973841,,,"This chapter describes the various strategies filoviruses use to escape host immune responses with a focus on innate immune and cell death pathways. Since filovirus replication can be efficiently blocked by interferon (IFN), filoviruses have evolved mechanisms to counteract both type I IFN induction and IFN response signaling pathways. Intriguingly, marburg- and ebolaviruses use different strategies to inhibit IFN signaling. This chapter also summarizes what is known about the role of IFN-stimulated genes (ISGs) in filovirus infection. These fall into three categories: those that restrict filovirus replication, those whose activation is inhibited by filoviruses, and those that have no measurable effect on viral replication. In addition to innate immunity, mammalian cells have evolved strategies to counter viral infections, including the induction of cell death and stress response pathways, and we summarize our current knowledge of how filoviruses interact with these pathways. Finally, this chapter delves into the interaction of EBOV with myeloid dendritic cells and macrophages and the associated inflammatory response, which differs dramatically between these cell types when they are infected with EBOV. In summary, we highlight the multifaceted nature of the host-viral interactions during filoviral infections.",,"['Olejnik, Judith', 'Hume, Adam J.', 'Leung, Daisy W.', 'Amarasinghe, Gaya K.', 'Basler, Christopher F.', 'Mühlberger, Elke']",,,,
,PMC,"Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia",http://dx.doi.org/10.3324/haematol.2016.150326,PMC5210249,,,"The prognosis of patients with acute myeloid leukemia in whom primary treatment fails remains very poor. In order to improve such patients’ outcome, we conducted a phase 2, prospective, multicenter trial to test the feasibility of a new sequential regimen, combining a short course of intensive chemotherapy and a reduced intensity-conditioning regimen, before allogeneic stem-cell transplantation. Twenty-four patients (median age, 47 years) with acute myeloid leukemia in primary treatment failure were included. Cytogenetic risk was poor in 15 patients (62%) and intermediate in nine (38%). The sequential regimen consisted of clofarabine (30 mg/m(2)/day) and cytosine arabinoside (1 g/m(2)/day) for 5 days, followed, after a 3-day rest, by reduced-intensity conditioning and allogeneic stem-cell transplantation combining cyclophosphamide (60 mg/kg), intravenous busulfan (3.2 mg/kg/day) for 2 days and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Patients in complete remission at day +120 received prophylactic donor lymphocyte infusion. Eighteen patients (75%) achieved complete remission. With a median follow-up of 24.6 months, the Kaplan-Meier estimate of overall survival was 54% (95% CI: 33–71) at 1 year and 38% (95% CI: 18–46) at 2 years. The Kaplan-Meier estimate of leukemia-free survival was 46% (95% CI: 26–64) at 1 year and 29% (95% CI: 13–48) at 2 years. The cumulative incidence of non-relapse mortality was 8% (95% CI: 1–24) at 1 year and 12% (95% CI: 3–19) at 2 years. Results from this phase 2 prospective multicenter trial endorsed the safety and efficacy of a clofarabine-based sequential reduced-toxicity conditioning regimen, which warrants further investigation. This study was registered at www.clinicaltrials.gov, identifier number: NCT01188174.",,"['Mohty, Mohamad', 'Malard, Florent', 'Blaise, Didier', 'Milpied, Noel', 'Socié, Gérard', 'Huynh, Anne', 'Reman, Oumédaly', 'Yakoub-Agha, Ibrahim', 'Furst, Sabine', 'Guillaume, Thierry', 'Tabrizi, Resa', 'Vigouroux, Stéphane', 'Peterlin, Pierre', 'El-Cheikh, Jean', 'Moreau, Philippe', 'Labopin, Myriam', 'Chevallier, Patrice']",,,,
,PMC,Medical School Hotline: Pacific Center for Emerging Infectious Diseases Research,,PMC5226018,,,,,"['Yanagihara, Richard', 'Nerurkar, Vivek R', 'Hui, George', 'Jacobs, Gwen A']",,,,
,PMC,The HIV-1 Envelope Glycoprotein Structure: Nailing down a Moving Target,http://dx.doi.org/10.1111/imr.12507,PMC5300090,,,"Structure determination of the HIV-1 envelope glycoprotein (Env) presented a number of challenges, but several high-resolution structures have now become available. In 2013, cryo-EM and x-ray structures of soluble, cleaved SOSIP Env trimers from the clade A BG505 strain provided the first glimpses into the Env trimer fold as well as more the variable regions. A recent cryo-EM structure of a native full-length trimer without any stabilizing mutations had the same core structure, but revealed new insights and features. A more comprehensive and higher resolution understanding of the glycan shield has also emerged, enabling a more complete representation of the Env glycoprotein structure. Complexes of Env trimers with broadly neutralizing antibodies have surprisingly illustrated that most of the Env surface can be targeted in natural infection and that the neutralizing epitopes are almost all composed of both peptide and glycan components. These structures have also provided further evidence of the inherent plasticity of Env and how antibodies can exploit this flexibility by perturbing or even stabilizing the trimer to facilitate neutralization. These breakthroughs have stimulated further design and stabilization of Env trimers as well as other platforms to generate trimers that now span multiple subtypes The Env trimers as immunogens have led to the first vaccine-induced neutralizing antibodies for structural and functional analyses.",,"['Ward, Andrew B.', 'Wilson, Ian A.']",,,,
,PMC,"Development of polymerase chain reaction-based diagnostic tests for detection of Malsoor virus & adenovirus isolated from Rousettus species of bats in Maharashtra, India",http://dx.doi.org/10.4103/ijmr.IJMR_1447_15,PMC5460580,28574020,CC BY-NC-SA,"BACKGROUND & OBJECTIVES: Bats are recognized as important reservoirs for emerging infectious disease and some unknown viral diseases. Two novel viruses, Malsoor virus (family Bunyaviridae, genus, Phlebovirus) and a novel adenovirus (AdV) (family, Adenoviridae genus, Mastadenovirus), were identified from Rousettus bats in the Maharashtra State of India. This study was done to develop and optimize real time reverse transcription - polymerase chain reaction (RT-PCR) assays for Malsoor virus and real time and nested PCR for adenovirus from Rousettus bats. METHODS: For rapid and accurate screening of Malsoor virus and adenovirus a nested polymerase chain reaction and TaqMan-based real-time PCR were developed. Highly conserved region of nucleoprotein gene of phleboviruses and polymerase gene sequence from the Indian bat AdV isolate polyprotein gene were selected respectively for diagnostic assay development of Malsoor virus and AdV. Sensitivity and specificity of assays were calculated and optimized assays were used to screen bat samples. RESULTS: Molecular diagnostic assays were developed for screening of Malsoor virus and AdV and those were found to be specific. Based on the experiments performed with different parameters, nested PCR was found to be more sensitive than real-time PCR; however, for rapid screening, real-time PCR can be used and further nested PCR can be used for final confirmation or in those laboratories where real-time facility/expertise is not existing. INTERPRETATION & CONCLUSIONS: This study reports the development and optimization of nested RT-PCR and a TaqMan-based real-time PCR for Malsoor virus and AdV. The diagnostic assays can be used for rapid detection of these novel viruses to understand their prevalence among bat population.",2017 Jan,"['Shete, Anita M.', 'Yadav, Pragya', 'Kumar, Vimal', 'Nikam, Tushar', 'Mehershahi, Kurosh', 'Kokate, Prasad', 'Patil, Deepak', 'Mourya, Devendra T.']",Indian J Med Res,,,
,PMC,Use of Liposomal Bupivacaine for Postoperative Analgesia in an Incisional Pain Model in Rats (Rattus norvegicus),,PMC5250497,,,"The local anesthetic bupivacaine is valuable for perioperative analgesia, but its use in the postoperative period is limited by its short duration of action. Here, we evaluated the application of a slow-release liposomal formulation of bupivacaine for postoperative analgesia. The aim was to assess whether liposomal bupivacaine effectively attenuates postoperative mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats (n = 36) were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC every 12 h for 2 d; buprenorphine HCl, 0.05 mg/kg SC every 12 h for 2 d (Bup HCl); 0.5% bupivacaine, 2 mg/kg SC local infiltration once (Bupi); liposomal bupivacaine, 1 mg/kg SC local infiltration once (Exp1); and liposomal bupivacaine, 6 mg/kg SC local infiltration once (Exp6). Mechanical and thermal hypersensitivity were evaluated daily on days –1, 0, 1, 2, 3, and 4. The saline group exhibited both hypersensitivities through all 4 evaluated postoperative days. Bup HCl attenuated mechanical hypersensitivity for 2 d and thermal hypersensitivity for 1 d. Bupi attenuated only thermal hypersensitivity for 4 d. Rats in the Exp1 group showed attenuation of both mechanical and thermal hypersensitivity for 4 d, and those in the Exp6 group had attenuation of mechanical hypersensitivity on day 0 and thermal hypersensitivity for 4 d. These data suggest that a single local infiltration of liposomal bupivacaine at a dose of 1 mg/kg SC effectively attenuates postoperative mechanical and thermal hypersensitivity for 4 d in a rat model of incisional pain.",,"['Kang, Stacey C', 'Jampachaisri, Katechan', 'Seymour, Travis L', 'Felt, Stephen A', 'Pacharinsak, Cholawat']",,,,
,PMC,Development of a Manikin-Based Performance Evaluation Method for Loose-Fitting Powered Air-Purifying Respirators,,PMC6258086,,,"OBJECTIVE: Loose-fitting powered air-purifying respirators (PAPRs) are increasingly being used in healthcare. NIOSH has previously used advanced manikin headforms to develop methods to evaluate filtering facepiece respirator fit; research has now begun to develop methods to evaluate PAPR performance using headforms. This preliminary study investigated the performance of PAPRs at different work rates to support development of a manikin-based test method. METHODS: Manikin penetration factors (mPF) of three models of loose-fitting PAPRs were measured at four different work rates (REST: 11 Lpm, LOW: 25 Lpm, MODERATE: 48 Lpm, and HIGH: 88 Lpm) using a medium-sized NIOSH static advanced headform mounted onto a torso. In-mask differential pressure was monitored throughout each test. Two condensation particle counters were used to measure the sodium chloride aerosol concentrations in the test chamber and also inside the PAPR facepiece over a 2-minute sample period. Two test system configurations were evaluated for returning air to the headform in the exhalation cycle (filtered and unfiltered). Geometric mean (GM) and 5th percentile mPFs for each model/work rate combination were computed. Analysis of variance tests were used to assess the variables affecting mPF. RESULTS: PAPR model, work rate, and test configuration significantly affected PAPR performance. PAPR airflow rates for the three models were approximately 185, 210, and 235 Lpm. All models achieved GM mPFs and 5(th) percentile mPFs greater than their designated Occupational Safety and Health Administration assigned protection factors despite negative minimum pressures observed for some work rate/model combinations. CONCLUSIONS: PAPR model, work rate, and test configuration affect PAPR performance. Advanced headforms have potential for assessing PAPR performance once test methods can be matured. A manikin-based inward leakage test method for PAPRs can be further developed using the knowledge gained from this study. Future studies should vary PAPR airflow rate to better understand the effects on performance. Additional future research is needed to evaluate the correlation of PAPR performance using advanced headforms to the performance measured with human subjects.",,"['Bergman, Mike', 'Basu, Rohan', 'Lei, Zhipeng', 'Niezgoda, George', 'Zhuang, Ziqing']",,,,
,PMC,Qualitative Analysis of Origins and Evolution of an Elastomeric Respirator-based Hospital Respiratory Protection Program,,PMC5849268,,,"Elastomeric respirators (elastomerics) may serve as one alternative to disposable N95 respirator use in healthcare. We explored factors which drove elastomeric adoption and continued use in a large academic medical center. We conducted semi-structured and focus group interviews in 2015 with a) 11 leadership key informants (KIs) with involvement in the respiratory protection program (RPP) when elastomerics were introduced and b) 11 healthcare workers (HCWs) recruited from hospital departments assigned to use elastomerics. Interview transcripts and responses were open-coded to capture emergent themes, which were collapsed into broader categories and iteratively refined. Factors identified by leadership KIs as influencing elastomeric adoption included: 1) N95 shortages during 2009’s H1N1 influenza pandemic and 2) the presence of trained, certified safety professionals who were familiar with respiratory protection requirements. Factors identified as influencing ongoing use of elastomerics included: 1) cleaning/decontamination practices, 2) storage, 3) safety culture, 4) HCW respirator knowledge, and 5) risk perception. HCW users expressed dissatisfaction related to breathing, communication and cleaning of elastomerics. Other themes included convenience use of N95s rather than assigned elastomerics, despite perceptions that elastomerics are more protective. Through semi-structured and focus group interviews, we learned that 1) leadership introduced elastomerics due to necessity but now face challenges related to ongoing use, and 2) HCWs were not satisfied with elastomerics for routine care and preferentially used N95s because they were conveniently available at point of use. Although the impetus behind incorporation of elastomerics was clear, the most complex themes related to sustainability of this form of RPP. These themes were used to inform a broader questionnaire and will address the utility of elastomerics as a feasible and acceptable practical alternative to N95s in healthcare.",,"['Hines, Stella E', 'Mueller, Nora', 'Oliver, Marc', 'Gucer, Patricia', 'McDiarmid, Melissa']",,,,
,PMC,Correlation of Nasal Mucosal Temperature With Subjective Nasal Patency in Healthy Individuals,http://dx.doi.org/10.1001/jamafacial.2016.1445,PMC5247324,,,"IMPORTANCE: Historically, otolaryngologists have focused on nasal resistance to airflow and minimum airspace cross-sectional area as objective measures of nasal obstruction using methods such as rhinomanometry and acoustic rhinometry. However, subjective sensation of nasal patency may be more associated with activation of cold receptors by inspired air than with respiratory effort. OBJECTIVE: To investigate whether subjective nasal patency correlates with nasal mucosal temperature in healthy subjects. DESIGN, SETTING, AND PARTICIPANTS: Twenty-two healthy adults were recruited for this study. Subjects first completed the Nasal Obstruction Symptom Evaluation (NOSE) and a unilateral visual analog scale (VAS) to quantify subjective nasal patency. A miniaturized thermocouple sensor was then used to record nasal mucosal temperature bilaterally in two locations along the nasal septum: at the vestibule and across from the inferior turbinate head. RESULTS: The range of temperature oscillations during the breathing cycle, defined as the difference between end-expiratory and end-inspiratory temperatures, was greater during deep breaths (ΔT(exp-insp) = 6.2 ± 2.6°C) than during resting breathing (ΔT(exp-insp) = 4.2 ± 2.3°C) in both locations (p < 10(−13)). Mucosal temperature measured at the right vestibule had a statistically significant correlation with both right-side VAS score (Pearson r = −0.55, p=0.0076) and NOSE score (Pearson r = −0.47, p=0.028). No other statistically significant correlations were found between mucosal temperature and subjective nasal patency scores. Nasal mucosal temperature was lower in the first cavity to be measured, which was the right cavity in all subjects. CONCLUSIONS AND RELEVANCE: The greater mucosal temperature oscillations during deep breathing is consistent with the common experience that airflow sensation is enhanced during deep breaths, thus supporting the hypothesis that mucosal cooling plays a central role in nasal airflow sensation. A possible correlation was found between subjective nasal patency scores and nasal mucosal temperature, but our results were inconsistent. The higher temperature in the left cavity suggests that the sensor irritated the nasal mucosa, affecting the correlation between patency scores and mucosal temperature. Future studies should consider non-contact temperature sensors to prevent mucosa irritation.",,"['Bailey, Ryan S.', 'Casey, Kevin P.', 'Pawar, Sachin S.', 'Garcia, Guilherme J. M.']",,,,
,PMC,Use of a fluorescent substrate to measure ACE2 activity in the mouse abdominal aorta,http://dx.doi.org/10.1007/978-1-4939-7030-8_5,PMC6442458,,,The use of fluorogenic substrates to measure enzymatic activity is widely used to understand function within different experimental models. ACE2 is important in understanding the balance between AngII and Ang-(1–7) and how this balance could then in turn influence hypertension or other disease outcomes. Here we describe a method to measure ACE2 activity in abdominal aorta of hyperlipidemic mice under both saline and AngII infusion.,,"['Wang, Yu', 'Cassis, Lisa A.', 'Thatcher, Sean E.']",,,,
,PMC,Computational and Experimental Studies of ADP-Ribosylation,http://dx.doi.org/10.1007/978-1-4939-6993-7_29,PMC5526223,,,"The macrodomains are a multifunctional protein family that function as receptors and enzymes acting on poly(ADP-ribose), ADP-ribosylated proteins, and other metabolites of nicotinamide adenine dinucleotide (NAD(+)). Several new functions for macrodomains, such as nucleic acid binding and protein/protein interaction, have recently been identified in this family. Here, we discuss methods for the identification of new macrodomains in viruses and the prediction of their function. This is followed by the expression and purification of these proteins following overexpression in bacterial cells and confirmation of folding and function using biophysical methods.",,"['Hammond, Robert G.', 'Tan, Xuan', 'Chan, Matthew', 'Goel, Anupam', 'Johnson, Margaret A.']",,,,
,PMC,Prescription practice of antihistamines for acute upper respiratory tract infections in pediatric patients in a local emergency department in Hong Kong,http://dx.doi.org/10.5847/wjem.j.1920-8642.2017.01.009,PMC5263036,,,"BACKGROUND: Currently there is very limited data in the literature assessing the prevalence of antihistamine prescription, and there is no local prevalence data about the prescription of antihistamine agents among primary practitioner and emergency physicians. The objectives are 1) to report the prevalence of antihistamine prescription for children less than 6 years old with acute upper respiratory infection and 2) to explore the associated factors for the prescription practice. METHODS: This is a cross-sectional study. All consecutive cases of paediatric patients aged 6 or below who presented to the emergency department during a study period of one week from April 1 to July 4, 2009 with diagnosis of acute upper respiratory infection were included. Totally 162 patients were included. RESULTS: Among the 162 cases, 141 (87%) patients were prescribed one antihistamine of any group. Sixty (37%) patients were prescribed two or more antihistamines. In multivariate logistic regression model, age was found to be significantly (P<0.001) associated with multiple antihistamine prescription (OR=1.042, 95%CI=1.02 to 1.06). Years of graduation of attending physician for more than 5 years was also a strong predictor of multiple antihistamine prescription (OR=4.654, 95%CI=2.20 to 9.84, P<0.001). CONCLUSION: In the local emergency department, patients’ age and the years of graduation from medical school of the attending physician were predictors of multiple antihistamine prescription for acute upper respiratory infections for children aged less than 6.",,"Lui, Chun Tat",,,,
,PMC,Serum protease activity in chronic kidney disease patients: The GANI_MED renal cohort,http://dx.doi.org/10.1177/1535370216684040,PMC5367655,,,"Serum or plasma proteases have been associated with various diseases including cancer, inflammation, or reno-cardiovascular diseases. We aimed to investigate whether the enzymatic activities of serum proteases are associated with the estimated glomerular filtration rate (eGFR) in patients with different stages of chronic kidney disease (CKD). Our study population comprised 268 participants of the “Greifswald Approach to Individualized Medicine” (GANI_MED) cohort. Enzymatic activity of aminopeptidase A, aminopeptidase B, alanyl (membrane) aminopeptidase, insulin-regulated aminopeptidase, puromycin-sensitive aminopeptidase, leucine aminopeptidase 3, prolyl-endopeptidase (PEP), dipeptidyl peptidase 4 (DPP4), angiotensin I-converting enzyme, and angiotensin I-converting enzyme 2 (ACE2) proteases was measured in serum. Linear regression of the respective protease was performed on kidney function adjusted for age and sex. Kidney function was modeled either by the continuous Modification of Diet in Renal Disease (MDRD)-based eGFR or dichotomized by eGFR < 15 mL/min/1.73 m(2) or <45 mL/min/1.73 m(2), respectively. Results with a false discovery rate below 0.05 were deemed statistically significant. Among the 10 proteases investigated, only the activities of ACE2 and DPP4 were correlated with eGFR. Patients with lowest eGFR exhibited highest DPP4 and ACE2 activities. DPP4 and PEP were correlated with age, but all other serum protease activities showed no associations with age or sex. Our data indicate that ACE2 and DPP4 enzymatic activity are associated with the eGFR in patients with CKD. This finding distinguishes ACE2 and DPP4 from other serum peptidases analyzed and clearly indicates that further analyses are warranted to identify the precise role of these serum ectopeptidases in the pathogenesis of CKD and to fully elucidate underlying molecular mechanisms. IMPACT STATEMENT: • Renal and cardiac diseases are very common and often occur concomitantly, resulting in increased morbidity and mortality. Understanding of molecular mechanisms linking both diseases is limited, available fragmentary data point to a role of the renin–angiotensin system (RAS) and, in particular, Ras-related peptidases. • Here, a comprehensive analysis of serum peptidase activities in patients with different stages of chronic kidney disease (CKD) is presented, with special emphasis given to RAS peptidases • The serum activities of the peptidases angiotensin I-converting enzyme 2 and dipeptidyl peptidase 4 were identified as closely associated with kidney function, specifically with the estimated glomerular filtration rate. The findings are discussed in the context of available data suggesting protective roles for both enzymes in reno-cardiac diseases. • The data add to our understanding of pathomechanisms underlying development and progression of CKD and indicate that both enzymes might represent potential pharmacological targets for the preservation of renal function.",,"['Wolke, Carmen', 'Teumer, Alexander', 'Endlich, Karlhans', 'Endlich, Nicole', 'Rettig, Rainer', 'Stracke, Sylvia', 'Fiene, Beate', 'Aymanns, Simone', 'Felix, Stephan B', 'Hannemann, Anke', 'Lendeckel, Uwe']",,,,
,PMC,Viral Respiratory Infections in Pre-term Infants During and After Hospitalization,http://dx.doi.org/10.1016/j.jpeds.2016.11.077,PMC5328856,,,"OBJECTIVE: To determine the burden of viral respiratory infections in pre-term infants both during and subsequent to Neonatal Intensive Care Unit (NICU) hospitalization and to compare this with term infants living in the community. STUDY DESIGN: From March 2013 through March 2015 we enrolled 189 newborns (96 term and 93 pre-term) into a prospective, longitudinal study obtaining nose/throat swabs within 7 days of birth, weekly while hospitalized and then monthly to four months after hospital discharge. Taqman array cards (TAC) were used to identify 16 viral respiratory pathogens by real time PCR. Demographic, clinical, and laboratory data were gathered from electronic medical records and parent interview while hospitalized with interval histories collected at monthly visits. The hospital course of all pre-term infants who underwent late-onset sepsis evaluations was reviewed. RESULTS: Over 119 weeks, we collected 618 nose/throat swabs from at risk pre-term infants in our Level IV regional NICU. Only four infants had viral respiratory infections, all less than 28 weeks gestation at birth. Two infants were symptomatic with the infections recognized by the clinical team. The daily risk of acquiring a respiratory viral infection in pre-term infants in the NICU was significantly lower than in the full term cohort living in the community. Once discharged from the hospital viral respiratory infections were common in all infants. CONCLUSIONS: Viral respiratory infections are infrequent in a NICU with strict infection prevention strategies, and do not appear to cause unrecognized illness. Both preterm and term infants living in the community quickly acquire respiratory viral infections.",,"['Caserta, Mary T.', 'Yang, Hongmei', 'Gill, Steven R', 'Holden-Wiltse, Jeanne', 'Pryhuber, Gloria']",,,,
,PMC,Structural and Molecular Evidence Suggesting Coronavirus-driven Evolution of Mouse Receptor,http://dx.doi.org/10.1074/jbc.M116.764266,PMC5313091,,,"Hosts and pathogens are locked in an evolutionary arms race. To infect mice, mouse hepatitis coronavirus (MHV) has evolved to recognize mouse CEACAM1a (mCEACAM1a) as its receptor. To elude MHV infections, mice may have evolved a variant allele from the Ceacam1a gene, called Ceacam1b, producing mCEACAM1b, which is a much poorer MHV receptor than mCEACAM1a. Previous studies showed that sequence differences between mCEACAM1a and mCEACAM1b in a critical MHV-binding CC′ loop partially account for the low receptor activity of mCEACAM1b, but detailed structural and molecular mechanisms for the differential MHV receptor activities of mCEACAM1a and mCEACAM1b remained elusive. Here we have determined the crystal structure of mCEACAM1b and identified the structural differences and additional residue differences between mCEACAM1a and mCEACAM1b that affect MHV binding and entry. These differences include conformational alterations of the CC′ loop as well as residue variations in other MHV-binding regions, including β-strands C′ and C′′ and loop C′C′′. Using pseudovirus entry and protein-protein binding assays, we show that substituting the structural and residue features from mCEACAM1b into mCEACAM1a reduced the viral receptor activity of mCEACAM1a, whereas substituting the reverse changes from mCEACAM1a into mCEACAM1b increased the viral receptor activity of mCEACAM1b. These results elucidate the detailed molecular mechanism for how mice may have kept pace in the evolutionary arms race with MHV by undergoing structural and residue changes in the MHV receptor, providing insight into this possible example of pathogen-driven evolution of a host receptor protein.",,"['Peng, Guiqing', 'Yang, Yang', 'Pasquarella, Joseph R.', 'Xu, Liqing', 'Qian, Zhaohui', 'Holmes, Kathryn V.', 'Li, Fang']",,,,
,PMC,Biological roles of glycans,http://dx.doi.org/10.1093/glycob/cww086,PMC5884436,,,"Simple and complex carbohydrates (glycans) have long been known to play major metabolic, structural and physical roles in biological systems. Targeted microbial binding to host glycans has also been studied for decades. But such biological roles can only explain some of the remarkable complexity and organismal diversity of glycans in nature. Reviewing the subject about two decades ago, one could find very few clear-cut instances of glycan-recognition-specific biological roles of glycans that were of intrinsic value to the organism expressing them. In striking contrast there is now a profusion of examples, such that this updated review cannot be comprehensive. Instead, a historical overview is presented, broad principles outlined and a few examples cited, representing diverse types of roles, mediated by various glycan classes, in different evolutionary lineages. What remains unchanged is the fact that while all theories regarding biological roles of glycans are supported by compelling evidence, exceptions to each can be found. In retrospect, this is not surprising. Complex and diverse glycans appear to be ubiquitous to all cells in nature, and essential to all life forms. Thus, >3 billion years of evolution consistently generated organisms that use these molecules for many key biological roles, even while sometimes coopting them for minor functions. In this respect, glycans are no different from other major macromolecular building blocks of life (nucleic acids, proteins and lipids), simply more rapidly evolving and complex. It is time for the diverse functional roles of glycans to be fully incorporated into the mainstream of biological sciences.",,"Varki, Ajit",,,,
,PMC,Comparison between Saliva and Nasopharyngeal Swab Specimens for Detection of Respiratory Viruses by Multiplex Reverse Transcription-PCR,http://dx.doi.org/10.1128/JCM.01704-16,PMC5228234,,,"Nasopharyngeal swabs (NPSs) are being widely used as specimens for multiplex real-time reverse transcription (RT)-PCR for respiratory virus detection. However, it remains unclear whether NPS specimens are optimal for all viruses targeted by multiplex RT-PCR. In addition, the procedure to obtain NPS specimens causes coughing in most patients, which possibly increases the risk of nosocomial spread of viruses. In this study, paired NPS and saliva specimens were collected from 236 adult male patients with suspected acute respiratory illnesses. Specimens were tested for 16 respiratory viruses by multiplex real-time RT-PCR. Among the specimens collected from the 236 patients, at least 1 respiratory virus was detected in 183 NPS specimens (77.5%) and 180 saliva specimens (76.3%). The rates of detection of respiratory viruses were comparable for NPS and saliva specimens (P = 0.766). Nine virus species and 349 viruses were isolated, 256 from NPS specimens and 273 from saliva specimens (P = 0.1574). Adenovirus was detected more frequently in saliva samples (P < 0.0001), whereas influenza virus type A and human rhinovirus were detected more frequently in NPS specimens (P = 0.0001 and P = 0.0289, respectively). The possibility of false-positive adenovirus detection from saliva samples was excluded by direct sequencing. In conclusion, neither of the sampling methods was consistently more sensitive than the other. We suggest that these cost-effective methods for detecting respiratory viruses in mixed NPS-saliva specimens might be valuable for future studies.",,"['Kim, Young-gon', 'Yun, Seung Gyu', 'Kim, Min Young', 'Park, Kwisung', 'Cho, Chi Hyun', 'Yoon, Soo Young', 'Nam, Myung Hyun', 'Lee, Chang Kyu', 'Cho, Yun-Jung', 'Lim, Chae Seung']",,,,
,PMC,Improved Detection of Respiratory Pathogens by Use of High-Quality Sputum with TaqMan Array Card Technology,http://dx.doi.org/10.1128/JCM.01805-16,PMC5228222,,,"New diagnostic platforms often use nasopharyngeal or oropharyngeal (NP/OP) swabs for pathogen detection for patients hospitalized with community-acquired pneumonia (CAP). We applied multipathogen testing to high-quality sputum specimens to determine if more pathogens can be identified relative to NP/OP swabs. Children (<18 years old) and adults hospitalized with CAP were enrolled over 2.5 years through the Etiology of Pneumonia in the Community (EPIC) study. NP/OP specimens with matching high-quality sputum (defined as ≤10 epithelial cells/low-power field [lpf] and ≥25 white blood cells/lpf or a quality score [q-score] definition of 2+) were tested by TaqMan array card (TAC), a multipathogen real-time PCR detection platform. Among 236 patients with matched specimens, a higher proportion of sputum specimens had ≥1 pathogen detected compared with NP/OP specimens in children (93% versus 68%; P < 0.0001) and adults (88% versus 61%; P < 0.0001); for each pathogen targeted, crossing threshold (C(T)) values were earlier in sputum. Both bacterial (361 versus 294) and viral detections (245 versus 140) were more common in sputum versus NP/OP specimens, respectively, in both children and adults. When available, high-quality sputum may be useful for testing in hospitalized CAP patients.",,"['Wolff, Bernard J.', 'Bramley, Anna M.', 'Thurman, Kathleen A.', 'Whitney, Cynthia G.', 'Whitaker, Brett', 'Self, Wesley H.', 'Arnold, Sandra R.', 'Trabue, Christopher', 'Wunderink, Richard G.', 'McCullers, Jon', 'Edwards, Kathryn M.', 'Jain, Seema', 'Winchell, Jonas M.']",,,,
,PMC,Prospective Biomarker Screening for Diagnosis of Invasive Aspergillosis in High-Risk Pediatric Patients,http://dx.doi.org/10.1128/JCM.01682-16,PMC5228221,,,"Combined biomarker screening is increasingly used to diagnose invasive aspergillosis (IA) in high-risk patients. In adults, the combination of galactomannan (GM) and fungal DNA detection has proven to be beneficial in the diagnosis of IA. Data in purely pediatric cohorts are scarce. Here, we monitored 39 children shortly before and after allogeneic stem cell transplantation twice weekly by use of a commercial GM enzyme-linked immunosorbent assay (ELISA) and a PCR assay based on amplification of the pan-Aspergillus ITS1/5.8S ribosomal operon. In addition, clinical data were recorded and classification of IA was performed according to the European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria. Among the 39 high-risk children, we identified 4 patients (10.3%) with probable and 2 (5.1%) with possible IA. All patients with probable IA were repeatedly positive for both tests (means of 9.5 and 6.8 positive GM and PCR samples, respectively), whereas both possible IA cases were detected by PCR. The sensitivity and specificity were, respectively, 67% and 89% for GM and 100% and 63% for PCR. Positive and negative predictive values were, respectively, 50% and 100% for GM and 27% and 100% for PCR. For the combined testing approach, both values were 100%. The number of positive samples seemed to be lower in patients undergoing antifungal therapy. Sporadically positive tests occurred in 12% (GM) and 42% (PCR) of unclassified patients. In summary, our data show that combined monitoring for GM and fungal DNA also results in a high diagnostic accuracy in pediatric patients. Future studies have to determine whether combined testing is suitable for early detection of subclinical disease and how antifungal prophylaxis impacts assay performance.",,"['Loeffler, Juergen', 'Hafner, Julia', 'Mengoli, Carlo', 'Wirth, Clemens', 'Heussel, Claus Peter', 'Löffler, Claudia', 'White, P. Lewis', 'Ullmann, Andrew J.', 'Michel, Denise', 'Wiegering, Verena', 'Wölfl, Matthias', 'Schlegel, Paul Gerhardt', 'Einsele, Hermann', 'Springer, Jan', 'Eyrich, Matthias']",,,,
,PMC,Identification of novel small molecule inhibitors against NS2B/NS3 serine protease from Zika virus,http://dx.doi.org/10.1016/j.antiviral.2016.12.016,PMC5627664,,,"Zika flavivirus infection during pregnancy appears to produce higher risk of microcephaly, and also causes multiple neurological problems such as Guillain–Barré syndrome. The Zika virus is now widespread in Central and South America, and is anticipated to become an increasing risk in the southern United States. With continuing global travel and the spread of the mosquito vector, the exposure is expected to accelerate, but there are no currently approved treatments against the Zika virus. The Zika NS2B/NS3 protease is an attractive drug target due to its essential role in viral replication. Our studies have identified several compounds with inhibitory activity (IC(50)) and binding affinity (K(D)) of ∼5-10 μM against the Zika NS2B-NS3 protease from testing 71 HCV NS3/NS4A inhibitors that were initially discovered by high-throughput screening of 40,967 compounds. Competition surface plasmon resonance studies and mechanism of inhibition analyses by enzyme kinetics subsequently determined the best compound to be a competitive inhibitor with a K(i) value of 9.5 μM. We also determined the X-ray structure of the Zika NS2B-NS3 protease in a “pre-open conformation”, a conformation never observed before for any flavivirus proteases. This provides the foundation for new structure-based inhibitor design.",,"['Lee, Hyun', 'Ren, Jinhong', 'Nocadello, Salvatore', 'Rice, Amy J.', 'Ojeda, Isabel', 'Light, Samuel', 'Minasov, George', 'Vargas, Jason', 'Nagarathnam, Dhanapalan', 'Anderson, Wayne F.', 'Johnson, Michael E.']",,,,
,PMC,An Intact Retroviral Gene Conserved in Spiny-Rayed Fishes for over 100 My,http://dx.doi.org/10.1093/molbev/msw262,PMC5939848,,,"We have identified a retroviral envelope gene with a complete, intact open reading frame (ORF) in 20 species of spiny-rayed fishes (Acanthomorpha). The taxonomic distribution of the gene, “percomORF”, indicates insertion into the ancestral lineage >110 Ma, making it the oldest known conserved gene of viral origin in a vertebrate genome. Underscoring its ancient provenence, percomORF exists as an isolated ORF within the intron of a widely conserved host gene, with no discernible proviral sequence nearby. Despite its remarkable age, percomORF retains canonical features of a retroviral glycoprotein, and tests for selection strongly suggest cooption for a host function. Retroviral envelope genes have been coopted for a role in placentogenesis by numerous lineages of mammals, including eutherians and marsupials, representing a variety of placental structures. Therefore percomORF’s presence within the group Percomorpha—unique among spiny-finned fishes in having evolved placentation and live birth—is especially intriguing.",,"['Henzy, Jamie E.', 'Gifford, Robert J.', 'Kenaley, Christopher P.', 'Johnson, Welkin E.']",,,,
,PMC,A snapshot of cryo‐EM,http://dx.doi.org/10.1002/pro.3088,PMC5192971,,,,,"Skiniotis, Georgios",,,,
,PMC,Respiratory Viral Infections in Chronic Lung Diseases,http://dx.doi.org/10.1016/j.ccm.2016.11.014,PMC5679206,,,,,"['Britto, Clemente J.', 'Brady, Virginia', 'Lee, Seiwon', 'Dela Cruz, Charles S.']",,,,
,PMC,Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding,http://dx.doi.org/10.1038/cr.2016.152,PMC5223232,,,"The global outbreak of SARS in 2002-2003 was caused by the infection of a new human coronavirus SARS-CoV. The infection of SARS-CoV is mediated mainly through the viral surface glycoproteins, which consist of S1 and S2 subunits and form trimer spikes on the envelope of the virions. Here we report the ectodomain structures of the SARS-CoV surface spike trimer in different conformational states determined by single-particle cryo-electron microscopy. The conformation 1 determined at 4.3 Å resolution is three-fold symmetric and has all the three receptor-binding C-terminal domain 1 (CTD1s) of the S1 subunits in “down” positions. The binding of the “down” CTD1s to the SARS-CoV receptor ACE2 is not possible due to steric clashes, suggesting that the conformation 1 represents a receptor-binding inactive state. Conformations 2-4 determined at 7.3, 5.7 and 6.8 Å resolutions are all asymmetric, in which one RBD rotates away from the “down” position by different angles to an “up” position. The “up” CTD1 exposes the receptor-binding site for ACE2 engagement, suggesting that the conformations 2-4 represent a receptor-binding active state. This conformational change is also required for the binding of SARS-CoV neutralizing antibodies targeting the CTD1. This phenomenon could be extended to other betacoronaviruses utilizing CTD1 of the S1 subunit for receptor binding, which provides new insights into the intermediate states of coronavirus pre-fusion spike trimer during infection.",,"['Gui, Miao', 'Song, Wenfei', 'Zhou, Haixia', 'Xu, Jingwei', 'Chen, Silian', 'Xiang, Ye', 'Wang, Xinquan']",,,,
,PMC,Immuno-engineered organoids for regulating the kinetics of B-cell development and antibody production,http://dx.doi.org/10.1038/nprot.2016.157,PMC6355337,,,"Induction of B-cell immunity against infection depends on the initiation of the germinal center (GC) reaction in secondary lymphoid organs. Ex vivo recapitulation of the GC reaction in 2D cultures results in transient cell growth, with poor yield and short-term survival. Furthermore, no reported 2D ex vivo system can modulate the kinetics of a GC-like phenotype or the rate of antibody class switching. This protocol describes a methodology for developing immune organoids that partially mimic the B-cell zone of a lymphoid tissue, for efficient and rapid generation of B cells with a GC-like phenotype from naive murine B cells. The organoid is composed of a bioadhesive protein, gelatin, that is transformed into an ionically cross-linked hydrated network using biocompatible silicate nanoparticles (siNps). We explain how to establish the immune organoid culture to sustain immune cell proliferation and transformation into a GC-like phenotype. Starting with cell encapsulation in digested lymphoid tissues, clusters of proliferating B cells with a GC-like phenotype can be generated in the organoids at controlled rates, within ~1 week. The culture methodology described here is currently the only one that allows the accelerated induction of a GC-like phenotype in B cells and supports a controllable immunoglobulin class-switching reaction. This method can be easily implemented in a typical tissue culture room by personnel with standard mammalian cell culture expertise.",,"['Purwada, Alberto', 'Singh, Ankur']",,,,
,PMC,MERS-CoV spike protein: a key target for antivirals,http://dx.doi.org/10.1080/14728222.2017.1271415,PMC5457961,,,"INTRODUCTION: The continual Middle East respiratory syndrome (MERS) threat highlights the importance of developing effective antiviral therapeutics to prevent and treat MERS coronavirus (MERS-CoV) infection. A surface spike (S) protein guides MERS-CoV entry into host cells by binding to cellular receptor dipeptidyl peptidase-4 (DPP4), followed by fusion between virus and host cell membranes. MERS-CoV S protein represents a key target for developing therapeutics to block viral entry and inhibit membrane fusion. AREAS COVERED: This review illustrates MERS-CoV S protein’s structure and function, particularly S1 receptor-binding domain (RBD) and S2 heptad repeat 1 (HR1) as therapeutic targets, and summarizes current advancement on developing anti-MERS-CoV therapeutics, focusing on neutralizing monoclonal antibodies (mAbs) and antiviral peptides. EXPERT OPINION: No anti-MERS-CoV therapeutic is approved for human use. Several S-targeting neutralizing mAbs and peptides have demonstrated efficacy against MERS-CoV infection, providing feasibility for development. Generally, human neutralizing mAbs targeting RBD are more potent than those targeting other regions of S protein. However, emergence of escape mutant viruses and mAb’s limitations make it necessary for combining neutralizing mAbs recognizing different neutralizing epitopes and engineering them with improved efficacy and reduced cost. Optimization of the peptide sequences is expected to produce next-generation anti-MERS-CoV peptides with improved potency.",,"['Du, Lanying', 'Yang, Yang', 'Zhou, Yusen', 'Lu, Lu', 'Li, Fang', 'Jiang, Shibo']",,,,
,PMC,Impairment of Cargo Transportation Caused by gbf1 Mutation Disrupts Vascular Integrity and Causes Hemorrhage in Zebrafish Embryos,http://dx.doi.org/10.1074/jbc.M116.767608,PMC5313103,,,"ADP-ribosylation factor GTPases are activated by guanine nucleotide exchange factors including Gbf1 (Golgi brefeldin A-resistant factor 1) and play important roles in regulating organelle structure and cargo-selective vesicle trafficking. However, the developmental role of Gbf1 in vertebrates remains elusive. In this study, we report the zebrafish mutant line tsu3994 that arises from N-ethyl-N-nitrosourea (ENU)-mediated mutagenesis and is characterized by prominent intracerebral and trunk hemorrhage. The mutant embryos develop hemorrhage accompanied by fewer pigments and shorter caudal fin at day 2 of development. The hemorrhage phenotype is caused by vascular breakage in a cell autonomous fashion. Positional cloning identifies a T → G nucleotide substitution in the 23rd exon of the gbf1 locus, resulting in a leucine → arginine substitution (L1246R) in the HDS2 domain. The mutant phenotype is mimicked by gbf1 knockouts and morphants, suggesting a nature of loss of function. Experimental results in mammalian cells show that the mutant form Gbf1(L1246R) is unable to be recruited to the Golgi apparatus and fails to activate Arf1 for recruiting COPI complex. The hemorrhage in tsu3994 mutants can be prevented partially and temporally by treating with the endoplasmic reticulum stress/apoptosis inhibitor tauroursodeoxycholic acid or by knocking down the proapoptotic gene baxb. Therefore, endothelial endoplasmic reticulum stress and subsequent apoptosis induced by gbf1 deficiency may account for the vascular collapse and hemorrhage.",,"['Chen, Jing', 'Wu, Xiaotong', 'Yao, Likun', 'Yan, Lu', 'Zhang, Lin', 'Qiu, Juhui', 'Liu, Xingfeng', 'Jia, Shunji', 'Meng, Anming']",,,,
,PMC,TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating Itch-Mediated Degradation of the Mitochondrial Adaptor MAVS,http://dx.doi.org/10.1128/MCB.00422-16,PMC5192085,,,"The host response to RNA virus infection consists of an intrinsic innate immune response and the induction of apoptosis as mechanisms to restrict viral replication. The mitochondrial adaptor molecule MAVS plays critical roles in coordinating both virus-induced type I interferon production and apoptosis; however, the regulation of MAVS-mediated apoptosis is poorly understood. Here, we show that the adaptor protein TAX1BP1 functions as a negative regulator of virus-induced apoptosis. TAX1BP1-deficient cells are highly sensitive to apoptosis in response to infection with the RNA viruses vesicular stomatitis virus and Sendai virus and to transfection with poly(I·C). TAX1BP1 undergoes degradation during RNA virus infection, and loss of TAX1BP1 is associated with apoptotic cell death. TAX1BP1 deficiency augments virus-induced activation of proapoptotic c-Jun N-terminal kinase (JNK) signaling. Virus infection promotes the mitochondrial localization of TAX1BP1 and concomitant interaction with the mitochondrial adaptor MAVS. TAX1BP1 recruits the E3 ligase Itch to MAVS to trigger its ubiquitination and degradation, and loss of TAX1BP1 or Itch results in increased MAVS protein expression. Together, these results indicate that TAX1BP1 functions as an adaptor molecule for Itch to target MAVS during RNA virus infection and thus restrict virus-induced apoptosis.",,"['Choi, Young Bong', 'Shembade, Noula', 'Parvatiyar, Kislay', 'Balachandran, Siddharth', 'Harhaj, Edward William']",,,,
,PMC,Role of Microglia Disturbances and Immune-Related Marker Abnormalities in Cortical Circuitry Dysfunction in Schizophrenia,http://dx.doi.org/10.1016/j.nbd.2016.12.019,PMC5303150,,,"Studies of genetics, serum cytokines, and autoimmune illnesses suggest that immune-related abnormalities are involved in the disease process of schizophrenia. Furthermore, direct evidence of cortical immune activation, including markedly elevated levels of many immune-related markers, have been reported in the prefrontal cortex in multiple cohorts of schizophrenia subjects. Within the prefrontal cortex in schizophrenia, deficits in the basilar dendritic spines of layer 3 pyramidal neurons and disturbances in inhibitory inputs to pyramidal neurons have also been commonly reported. Interestingly, microglia, the resident immune-related cells of the brain, also regulate excitatory and inhibitory input to pyramidal neurons. Consequently, in this review, we describe the cytological and molecular evidence of immune activation that has been reported in the brains of individuals with schizophrenia and the potential links between these immune-related disturbances with previously reported disturbances in pyramidal and inhibitory neurons in the disorder. Finally, we discuss the role that activated microglia may play in connecting these observations and as potential therapeutic treatment targets in schizophrenia.",,"Volk, David W.",,,,
,PMC,Characteristics associated with clinical severity and inflammatory phenotype of naturally occurring virus-induced exacerbations of asthma in adults,http://dx.doi.org/10.1016/j.rmed.2016.12.010,PMC5462105,,,"BACKGROUND: In experimental studies viral infections have been shown to induce type 2 inflammation in asthmatics, but whether this is a feature of naturally occurring virus-induced asthma exacerbations is unknown. Thymic stromal lymphopoietin (TSLP) released from the airway epithelium in response to damage, has been suggested as a link between viral infection and type 2 inflammation, but the role of TSLP in asthma exacerbations is unknown. OBJECTIVE: To assess whether type 2 inflammation, as measured by sputum eosinophils and fractional exhaled nitric oxide (FeNO), is a feature of naturally occurring virus-induced exacerbations of asthma and whether TSLP is associated with this type 2 inflammation. METHODS: Patients presenting to hospital with acute asthma were examined during the exacerbation, and after 4 weeks recovery. The assessments included spirometry, FeNO and induced sputum for differential counts and TSLP mRNA levels. Nasal swabs were collected for viral detection. RESULTS: Sputum eosinophils and FeNO were similar between virus-positive (n=44) and negative patients (n=44). In virus-positive patients, TSLP expression was lower at exacerbation than follow-up (p=0.03). High TSLP at exacerbation was associated with lower sputum eosinophils (p=0.01) and higher FEV1 (p=0.03). In virus-positive patients, %-predicted FEV1 negatively correlated with both FeNO and sputum eosinophils (p=0.02 and p=0.05, respectively). CONCLUSION: Our findings support that type 2 inflammation is present in patients during virus-induced asthma exacerbations, to the same degree as non-viral exacerbations, and correlate negatively with FEV1. However, in virus-positive patients, high TSLP expression during exacerbation was associated with low sputum eosinophils, suggesting that the effect of TSLP in vivo, in the setting of an asthma exacerbation, might be different than the type 2 inducing effects observed in experimental studies.",,"['Bjerregaard, Asger', 'Laing, Ingrid A.', 'Poulsen, Nadia', 'Backer, Vibeke', 'Sverrild, Asger', 'Fally, Markus', 'Khoo, Siew-Kim', 'Barrett, Lucy', 'Baltic, Svetlana', 'Thompson, Philip J.', 'Chidlow, Glenys', 'Sikazwe, Chisha', 'Smith, David W', 'Bochkov, Yury A.', 'Le Souëf, Peter', 'Porsbjerg, Celeste']",,,,
,PMC,Viral pneumonia in patients with hematologic malignancy or hematopoietic stem cell transplantion,http://dx.doi.org/10.1016/j.ccm.2016.11.002,PMC5373482,,,,,"['Vakil, Erik', 'Evans, Scott E.']",,,,
,PMC,Structural Biology of the Arterivirus nsp11 Endoribonucleases,http://dx.doi.org/10.1128/JVI.01309-16,PMC5165224,,,"Endoribonuclease (NendoU) is unique and conserved as a major genetic marker in nidoviruses that infect vertebrate hosts. Arterivirus nonstructural protein 11 (nsp11) was shown to have NendoU activity and play essential roles in the viral life cycle. Here, we report three crystal structures of porcine reproductive and respiratory syndrome virus (PRRSV) and equine arteritis virus (EAV) nsp11 mutants. The structures of arterivirus nsp11 contain two conserved compact domains: the N-terminal domain (NTD) and C-terminal domain (CTD). The structures of PRRSV and EAV endoribonucleases are similar and conserved in the arterivirus, but they are greatly different from that of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoV), representing important human pathogens in the Nidovirales order. The catalytic center of NendoU activity is located in the CTD, where a positively charged groove is next to the key catalytic residues conserved in nidoviruses. Although the NTD is nearly identical, the catalytic region of the arterivirus nsp11 family proteins is remarkably flexible, and the oligomerization may be concentration dependent. In summary, our structures provide new insight into this key multifunctional NendoU family of proteins and lay a foundation for better understanding of the molecular mechanism and antiviral drug development. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) and equine arteritis virus are two major members of the arterivirus family. PRRSV, a leading swine pathogen, causes reproductive failure in breeding stock and respiratory tract illness in young pigs. Due to the lack of a suitable vaccine or effective drug treatment and the quick spread of these viruses, infected animals either die quickly or must be culled. PRRSV costs the swine industry around $644 million annually in the United States and almost €1.5 billion in Europe every year. To find a way to combat these viruses, we focused on the essential viral nonstructural protein 11 (nsp11). nsp11 is associated with multiple functions, such as RNA processing and suppression of the infected host innate immunity system. The three structures solved in this study provide new insight into the molecular mechanisms of this crucial protein family and will benefit the development of new treatments against these deadly viruses.",,"['Zhang, Manfeng', 'Li, Xiaorong', 'Deng, Zengqin', 'Chen, Zhenhang', 'Liu, Yang', 'Gao, Yina', 'Wu, Wei', 'Chen, Zhongzhou']",,,,
,PMC,Recombinant Receptor-Binding Domains of Multiple Middle East Respiratory Syndrome Coronaviruses (MERS-CoVs) Induce Cross-Neutralizing Antibodies against Divergent Human and Camel MERS-CoVs and Antibody Escape Mutants,http://dx.doi.org/10.1128/JVI.01651-16,PMC5165220,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) binds to cellular receptor dipeptidyl peptidase 4 (DPP4) via the spike (S) protein receptor-binding domain (RBD). The RBD contains critical neutralizing epitopes and serves as an important vaccine target. Since RBD mutations occur in different MERS-CoV isolates and antibody escape mutants, cross-neutralization of divergent MERS-CoV strains by RBD-induced antibodies remains unknown. Here, we constructed four recombinant RBD (rRBD) proteins with single or multiple mutations detected in representative human MERS-CoV strains from the 2012, 2013, 2014, and 2015 outbreaks, respectively, and one rRBD protein with multiple changes derived from camel MERS-CoV strains. Like the RBD of prototype EMC2012 (EMC-RBD), all five RBDs maintained good antigenicity and functionality, the ability to bind RBD-specific neutralizing monoclonal antibodies (MAbs) and the DPP4 receptor, and high immunogenicity, able to elicit S-specific antibodies. They induced potent neutralizing antibodies cross-neutralizing 17 MERS pseudoviruses expressing S proteins of representative human and camel MERS-CoV strains identified during the 2012-2015 outbreaks, 5 MAb escape MERS-CoV mutants, and 2 live human MERS-CoV strains. We then constructed two RBDs mutated in multiple key residues in the receptor-binding motif (RBM) of RBD and demonstrated their strong cross-reactivity with anti-EMC-RBD antibodies. These RBD mutants with diminished DPP4 binding also led to virus attenuation, suggesting that immunoevasion after RBD immunization is accompanied by loss of viral fitness. Therefore, this study demonstrates that MERS-CoV RBD is an important vaccine target able to induce highly potent and broad-spectrum neutralizing antibodies against infection by divergent circulating human and camel MERS-CoV strains. IMPORTANCE MERS-CoV was first identified in June 2012 and has since spread in humans and camels. Mutations in its spike (S) protein receptor-binding domain (RBD), a key vaccine target, have been identified, raising concerns over the efficacy of RBD-based MERS vaccines against circulating human and camel MERS-CoV strains. Here, we constructed five vaccine candidates, designated 2012-RBD, 2013-RBD, 2014-RBD, 2015-RBD, and Camel-RBD, containing single or multiple mutations in the RBD of representative human and camel MERS-CoV strains during the 2012-2015 outbreaks. These RBD-based vaccine candidates maintained good functionality, antigenicity, and immunogenicity, and they induced strong cross-neutralizing antibodies against infection by divergent pseudotyped and live MERS-CoV strains, as well as antibody escape MERS-CoV mutants. This study provides impetus for further development of a safe, highly effective, and broad-spectrum RBD-based subunit vaccine to prevent MERS-CoV infection.",,"['Tai, Wanbo', 'Wang, Yufei', 'Fett, Craig A.', 'Zhao, Guangyu', 'Li, Fang', 'Perlman, Stanley', 'Jiang, Shibo', 'Zhou, Yusen', 'Du, Lanying']",,,,
,PMC,Creating an Artificial Tail Anchor as a Novel Strategy To Enhance the Potency of Peptide-Based HIV Fusion Inhibitors,http://dx.doi.org/10.1128/JVI.01445-16,PMC5165219,,,"20 (enfuvirtide) and other peptides derived from the human immunodeficiency virus type 1 (HIV-1) gp41 C-terminal heptad repeat (CHR) region inhibit HIV fusion by binding to the hydrophobic grooves on the N-terminal heptad repeat (NHR) trimer and blocking six-helix-bundle (6-HB) formation. Several strategies focusing on the binding grooves of the NHR trimer have been adopted to increase the antiviral activity of the CHR peptides. Here, we developed a novel and simple strategy to greatly enhance the potency of the existing peptide-based HIV fusion inhibitors. First, we identified a shallow pocket adjacent to the groove in the N-terminal region of NHR trimer as a new drug target, and then we designed several short artificial peptides to fit this target. After the addition of IDL (Ile-Asp-Leu) to the C terminus of CHR peptide WQ or MT-WQ, the conjugated peptides, WQ-IDL and MT-WQ-IDL, showed much more potent activities than WQ and T20, respectively, in inhibiting HIV-1 IIIB infection. WQ-IDL and MT-WQ-IDL were also more effective than WQ in blocking HIV-1 Env-mediated membrane fusion and had higher levels of binding affinity with NHR peptide N46. We solved the crystal structure of the 6-HB formed by MT-WQ-IDL and N46 and found that, besides the N-terminal MT hook tail, the IDL tail anchor of MT-WQ-IDL also binds with the shallow hydrophobic pocket outside the groove of the NHR trimer, resulting in enhanced inhibition of HIV-1 fusion with the target cell. It is expected that this novel approach can be widely used to improve the potency of peptidic fusion inhibitors against other enveloped viruses with class I fusion proteins. IMPORTANCE The hydrophobic groove of the human immunodeficiency virus type 1 (HIV-1) gp41 NHR trimer has been known as the classic drug target to develop fusion inhibitors derived from the gp41 CHR. Here, we developed a novel and simple strategy to improve the existing peptide-based HIV fusion inhibitors. We identified a shallow pocket adjacent to the groove in the NHR trimer and added a short artificial peptide consisting of three amino acids (IDL) to the C terminus of a fusion inhibitor to fit this new target. The inhibition activity of this new conjugated peptide was significantly enhanced, by 77-fold, making it much more potent than T20 (enfuvirtide) and suggesting that the IDL tail can be adopted for optimizing existing HIV-1 CHR peptide fusion inhibitors. This new approach of identifying a potential binding pocket outside the traditional target and creating an artificial tail anchor can be widely applied to design novel fusion inhibitors against other class I enveloped viruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV).",,"['Su, Shan', 'Zhu, Yun', 'Ye, Sheng', 'Qi, Qianqian', 'Xia, Shuai', 'Ma, Zhenxuan', 'Yu, Fei', 'Wang, Qian', 'Zhang, Rongguang', 'Jiang, Shibo', 'Lu, Lu']",,,,
,PMC,Pivotal Role of Receptor-Interacting Protein Kinase 1 and Mixed Lineage Kinase Domain-Like in Neuronal Cell Death Induced by the Human Neuroinvasive Coronavirus OC43,http://dx.doi.org/10.1128/JVI.01513-16,PMC5165216,,,"Human coronaviruses (HCoV) are respiratory pathogens with neuroinvasive, neurotropic, and neurovirulent properties, highlighting the importance of studying the potential implication of these viruses in neurological diseases. The OC43 strain (HCoV-OC43) was reported to induce neuronal cell death, which may participate in neuropathogenesis. Here, we show that HCoV-OC43 harboring two point mutations in the spike glycoprotein (rOC/U(s183–241)) was more neurovirulent than the wild-type HCoV-OC43 (rOC/ATCC) in mice and induced more cell death in murine and human neuronal cells. To evaluate the role of regulated cell death (RCD) in HCoV-OC43-mediated neural pathogenesis, we determined if knockdown of Bax, a key regulator of apoptosis, or RIP1, a key regulator of necroptosis, altered the percentage of neuronal cell death following HCoV-OC43 infection. We found that Bax-dependent apoptosis did not play a significant role in RCD following infection, as inhibition of Bax expression mediated by RNA interference did not confer cellular protection against the cell death process. On the other hand, we demonstrated that RIP1 and MLKL were involved in neuronal cell death, as RIP1 knockdown and chemical inhibition of MLKL significantly increased cell survival after infection. Taken together, these results indicate that RIP1 and MLKL contribute to necroptotic cell death after HCoV-OC43 infection to limit viral replication. However, this RCD could lead to neuronal loss in the mouse CNS and accentuate the neuroinflammation process, reflecting the severity of neuropathogenesis. IMPORTANCE Because they are naturally neuroinvasive and neurotropic, human coronaviruses are suspected to participate in the development of neurological diseases. Given that the strain OC43 is neurovirulent in mice and induces neuronal cell death, we explored the neuronal response to infection by characterizing the activation of RCD. Our results revealed that classical apoptosis associated with the Bax protein does not play a significant role in HCoV-OC43-induced neuronal cell death and that RIP1 and MLKL, two cellular proteins usually associated with necroptosis (an RCD back-up system when apoptosis is not adequately induced), both play a pivotal role in the process. As necroptosis disrupts cellular membranes and allows the release of damage-associated molecular patterns (DAMP) and possibly induces the production of proinflammatory cytokines, it may represent a proinflammatory cell death mechanism that contributes to excessive neuroinflammation and neurodegeneration and eventually to neurological disorders after a coronavirus infection.",,"['Meessen-Pinard, Mathieu', 'Le Coupanec, Alain', 'Desforges, Marc', 'Talbot, Pierre J.']",,,,
,PMC,CD8(+) T Cells and Macrophages Regulate Pathogenesis in a Mouse Model of Middle East Respiratory Syndrome,http://dx.doi.org/10.1128/JVI.01825-16,PMC5165197,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) is an important emerging pathogen that was first described in 2012. While the cell surface receptor for MERS-CoV has been identified as dipeptidyl peptidase 4 (DPP4), the mouse DPP4 homologue does not allow virus entry into cells. Therefore, development of mouse models of MERS-CoV has been hampered by the fact that MERS-CoV does not replicate in commonly available mouse strains. We have previously described a mouse model in which mDPP4 was replaced with hDPP4 such that hDPP4 is expressed under the endogenous mDPP4 promoter. In this study, we used this mouse model to analyze the host response to MERS-CoV infection using immunological assays and transcriptome analysis. Depletion of CD4(+) T cells, CD8(+) T cells, or macrophages has no effect on MERS-CoV replication in the lungs of infected mice. However, we found that depletion of CD8(+) T cells protects and depletion of macrophages exacerbates MERS-CoV-induced pathology and clinical symptoms of disease. Overall, we demonstrate an important role for the inflammatory response in regulating MERS-CoV pathogenesis in vivo. IMPORTANCE The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic respiratory virus that emerged from zoonotic sources in 2012. Human infections are still occurring throughout Saudi Arabia at a 38% case fatality rate, with the potential for worldwide spread via air travel. In this work, we identify the host response to the virus and identify inflammatory pathways and cell populations that are critical for protection from severe lung disease. By understanding the immune response to MERS-CoV we can develop targeted therapies to inhibit pathogenesis in the future.",,"['Coleman, Christopher M.', 'Sisk, Jeanne M.', 'Halasz, Gabor', 'Zhong, Jixin', 'Beck, Sarah E.', 'Matthews, Krystal L.', 'Venkataraman, Thiagarajan', 'Rajagopalan, Sanjay', 'Kyratsous, Christos A.', 'Frieman, Matthew B.']",,,,
,PMC,Clinical Isolates of Human Coronavirus 229E Bypass the Endosome for Cell Entry,http://dx.doi.org/10.1128/JVI.01387-16,PMC5165181,,,"Human coronavirus 229E (HCoV-229E), a causative agent of the common cold, enters host cells via two distinct pathways: one is mediated by cell surface proteases, particularly transmembrane protease serine 2 (TMPRSS2), and the other by endosomal cathepsin L. Thus, specific inhibitors of these proteases block virus infection. However, it is unclear which of these pathways is actually utilized by HCoV-229E in the human respiratory tract. Here, we examined the mechanism of cell entry used by a pseudotyped virus bearing the HCoV-229E spike (S) protein in the presence or absence of protease inhibitors. We found that, compared with a laboratory strain isolated in 1966 and passaged for a half century, clinical isolates of HCoV-229E were less likely to utilize cathepsin L; rather, they showed a preference for TMPRSS2. Two amino acid substitutions (R642M and N714K) in the S protein of HCoV-229E clinical isolates altered their sensitivity to a cathepsin L inhibitor, suggesting that these amino acids were responsible for cathepsin L use. After 20 passages in HeLa cells, the ability of the isolate to use cathepsin increased so that it was equal to that of the laboratory strain; this increase was caused by an amino acid substitution (I577S) in the S protein. The passaged virus showed a reduced ability to replicate in differentiated airway epithelial cells cultured at an air-liquid interface. These results suggest that the endosomal pathway is disadvantageous for HCoV-229E infection of human airway epithelial cells; therefore, clinical isolates are less able to use cathepsin. IMPORTANCE Many enveloped viruses enter cells through endocytosis. Viral spike proteins drive the fusion of viral and endosomal membranes to facilitate insertion of the viral genome into the cytoplasm. Human coronavirus 229E (HCoV-229E) utilizes endosomal cathepsin L to activate the spike protein after receptor binding. Here, we found that clinical isolates of HCoV-229E preferentially utilize the cell surface protease TMPRSS2 rather than endosomal cathepsin L. The endosome is a main site of Toll-like receptor recognition, which then triggers an innate immune response; therefore, HCoV-229E presumably evolved to bypass the endosome by entering the cell via TMPRSS2. Thus, the virus uses a simple mechanism to evade the host innate immune system. Therefore, therapeutic agents for coronavirus-mediated diseases, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), should target cell surface TMPRSS2 rather than endosomal cathepsin.",,"['Shirato, Kazuya', 'Kanou, Kazuhiko', 'Kawase, Miyuki', 'Matsuyama, Shutoku']",,,,
,PMC,MicroRNA Regulation of RNA Virus Replication and Pathogenesis,http://dx.doi.org/10.1016/j.molmed.2016.11.003,PMC5836316,,,"microRNAs (miRNAs) are non-coding RNAs that regulate many processes within a cell by manipulating protein levels through direct binding to mRNA and influencing translation efficiency, or mRNA abundance. Recent evidence demonstrates that miRNAs can also affect RNA virus replication and pathogenesis through direct binding to the RNA virus genome or through virus-mediated changes in the host transcriptome. Here, we review the current knowledge on the interaction between RNA viruses and cellular miRNAs. We also discuss how cell and tissue-specific expression of miRNAs can directly affect viral pathogenesis. Understanding the role of cellular miRNAs during viral infection may lead to the identification of novel mechanisms to block RNA virus replication or cell-specific regulation of viral vector targeting.",,"['Trobaugh, Derek W.', 'Klimstra, William B.']",,,,
,PMC,Functional genomics reveals that tumors with activating phosphoinositide 3-kinase mutations are dependent on accelerated protein turnover,http://dx.doi.org/10.1101/gad.290122.116,PMC5238728,,,"Activating mutations in the phosphoinositide 3-kinase (PI3K) signaling pathway are frequently identified in cancer. To identify pathways that support PI3K oncogenesis, we performed a genome-wide RNAi screen in isogenic cell lines harboring wild-type or mutant PIK3CA to search for PI3K synthetic-lethal (SL) genes. A combined analysis of these results with a meta-analysis of two other large-scale RNAi screening data sets in PI3K mutant cancer cell lines converged on ribosomal protein translation and proteasomal protein degradation as critical nononcogene dependencies for PI3K-driven tumors. Genetic or pharmacologic inhibition of either pathway alone, but not together, selectively killed PI3K mutant tumor cells in an mTOR-dependent manner. The expression of ribosomal and proteasomal components was significantly up-regulated in primary human colorectal tumors harboring PI3K pathway activation. Importantly, a PI3K SL gene signature containing the top hits of the SL genes identified in our meta-analysis robustly predicted overall patient survival in colorectal cancer, especially among patients with tumors with an activated PI3K pathway. These results suggest that disruption of protein turnover homeostasis via ribosome or proteasome inhibition may be a novel treatment strategy for PI3K mutant human tumors.",,"['Davoli, Teresa', 'Mengwasser, Kristen E.', 'Duan, Jingjing', 'Chen, Ting', 'Christensen, Camilla', 'Wooten, Eric C.', 'Anselmo, Anthony N.', 'Li, Mamie Z.', 'Wong, Kwok-Kin', 'Kahle, Kristopher T.', 'Elledge, Stephen J.']",,,,
,PMC,Vaccination in Hajj: An Overview of the Recent Findings,http://dx.doi.org/10.4103/2008-7802.195826,PMC5200976,28105294,CC BY-NC-SA,"BACKGROUND: About two million people annually travel to Kingdom of Saudi Arabia to perform Hajj. The pilgrims may be at risk of exposure to communicable diseases in this mass gathering and their vaccination against contagious diseases can prevent many morbidities and mortalities. The aim of our study was to review the papers which evaluated effectiveness and compliance of the vaccines applied in Hajj. METHODS: We used PubMed and Scopus to search international medical databases. The key words were as follows: Hajj, Haj, vaccine, vaccination, and immunization. The time interval of the search was from the beginning of 2010 to May 23, 2016. One hundred and thirty papers were extracted, and their contents were subsequently reviewed after title and abstract screenings. The original articles were included in the study and non-English articles were excluded from the study. RESULTS: Considering the extracted papers, almost all pilgrims were vaccinated against meningococcal diseases. Using of influenza and pneumococcal vaccine rates were different among the pilgrims. The other vaccines have been taking according to specific conditions. CONCLUSIONS: The findings regarding influenza vaccine effectiveness are contradictory. A few studies confirmed the flu vaccine effectiveness while some others rejected its usefulness. Meningococcal immunization is an effective preventive tool with high compliance for Hajj pilgrims. Further investigations are recommended for the other vaccines.",2016 Dec 15,"['Razavi, Seyed Mansour', 'Saeednejad, Mina', 'Salamati, Payman']",Int J Prev Med,,,
,PMC,The Association Between Hospital Capacity Strain and Inpatient Outcomes in Highly Developed Countries: A Systematic Review,http://dx.doi.org/10.1007/s11606-016-3936-3,PMC5442002,,,"BACKGROUND: Increases in patient needs can strain hospital resources, which may worsen care quality and outcomes. This systematic literature review sought to understand whether hospital capacity strain is associated with worse health outcomes for hospitalized patients and to evaluate benefits and harms of health system interventions to improve care quality during times of hospital capacity strain. METHODS: Parallel searches were conducted in MEDLINE, CINAHL, the Cochrane Library, and reference lists from 1999-2015. Two reviewers assessed study eligibility. We included English-language studies describing the association between capacity strain (high census, acuity, turnover, or an indirect measure of strain such as delayed admission) and health outcomes or intermediate outcomes for children and adults hospitalized in highly developed countries. We also included studies of health system interventions to improve care during times of capacity strain. Two reviewers extracted data and assessed risk of bias using the Newcastle-Ottawa Score for observational studies and the Cochrane Collaboration Risk of Bias Assessment Tool for experimental studies. RESULTS: Of 5,702 potentially relevant studies, we included 44 observational and 8 experimental studies. There was marked heterogeneity in the metrics used to define capacity strain, hospital settings, and overall study quality. Mortality increased during times of capacity strain in 18 of 30 studies and in 9 of 12 studies in intensive care unit settings. No experimental studies were randomized, and none demonstrated an improvement in health outcomes after implementing the intervention. The pediatric literature is very limited; only six observational studies included children. There was insufficient study homogeneity to perform meta-analyses. DISCUSSION: In highly developed countries, hospital capacity strain is associated with increased mortality and worsened health outcomes. Evidence-based solutions to improve outcomes during times of capacity strain are needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11606-016-3936-3) contains supplementary material, which is available to authorized users.",,"['Eriksson, Carl O.', 'Stoner, Ryan C.', 'Eden, Karen B.', 'Newgard, Craig D.', 'Guise, Jeanne-Marie']",,,,
,PMC,Luciferase-tagged wild-type and tropism-deficient mouse cytomegaloviruses reveal early dynamics of host colonization following peripheral challenge,http://dx.doi.org/10.1099/jgv.0.000642,PMC6542255,,,"Cytomegaloviruses (CMVs) establish persistent, systemic infections and cause disease by maternal–foetal transfer, suggesting that their dissemination is a key target for antiviral intervention. Late clinical presentation has meant that human CMV (HCMV) dissemination is not well understood. Murine CMV (MCMV) provides a tractable model. Whole mouse imaging of virus-expressed luciferase has proved a useful way to track systemic infections. MCMV, in which the abundant lytic gene M78 was luciferase-tagged via a self-cleaving peptide (M78-LUC), allowed serial, unbiased imaging of systemic and peripheral infection without significant virus attenuation. Ex vivo luciferase imaging showed greater sensitivity than plaque assay, and revealed both well-known infection sites (the lungs, lymph nodes, salivary glands, liver, spleen and pancreas) and less explored sites (the bone marrow and upper respiratory tract). We applied luciferase imaging to tracking MCMV lacking M33, a chemokine receptor conserved in HCMV and a proposed anti-viral drug target. M33-deficient M78-LUC colonized normally in peripheral sites and local draining lymph nodes but spread poorly to the salivary gland, suggesting a defect in vascular transport consistent with properties of a chemokine receptor.",,"['Farrell, Helen', 'Oliveira, Martha', 'Macdonald, Kate', 'Yunis, Joseph', 'Mach, Michael', 'Bruce, Kimberley', 'Stevenson, Philip', 'Cardin, Rhonda', 'Davis-Poynter, Nicholas']",,,,
,PMC,Heterologous boosting with recombinant VSV-846 in BCG-primed mice confers improved protection against Mycobacterium infection,http://dx.doi.org/10.1080/21645515.2016.1261229,PMC5404650,,,"Tuberculosis (TB) remains a major health problem worldwide, and the development of effective vaccines is urgently needed. Vaccination strategies based on heterologous prime–boost protocols using Mycobacterium bovis bacillus Calmette-Guérin (BCG) as primer and modified vaccinia virus Ankara strain expressing the mycobacterial antigen Ag85A (MVA85A) as booster may increase the protective efficacy of BCG. In addition, vaccination with the recombinant viral vaccine vesicular stomatitis virus (VSV)-846 (Rv3615c, Mtb10.4, and Rv2660c) can elicit a remarkable T-cell-mediated immune response and provide an effective long-term protection after the BCG challenge. In this study, we used VSV-846 to boost BCG and evaluated its immunogenicity in BALB/c mice. In this prime–boost approach, boosting with VSV-846 significantly enhanced IFN-γ CD4 T cell responses, which are crucial for anti-TB immune responses. Moreover, VSV-846 boosting significantly reduced pathology compared with mock vaccination, and decreased the bacterial loads in lung tissues compared with BCG or VSV-846 vaccination alone. The analysis of vaccine-induced immunity identified that polyfunctional T cells might contribute to the enhanced protection by VSV-846 boosting. This study proved that viral booster VSV-846 in mice improved the protection against mycobacteria infection, which could be helpful in designing an efficient vaccination strategy against TB in humans.",,"['Zhang, Ming', 'Dong, Chunsheng', 'Xiong, Sidong']",,,,
,PMC,Preclinical study and clinical trial of a novel therapeutic vaccine against multi-drug resistant tuberculosis,http://dx.doi.org/10.1080/21645515.2017.1264781,PMC5328238,,,"[Purpose] Multi-drug resistant (MDR), Mycobacterium tuberculosis (TB) is a big problem in the world. We have developed novel TB therapeutic vaccine (HVJ-E/HSP65 DNA +IL-12 DNA). [Methods and Results] DNA vaccine expressing TB heat shock protein 65 and IL-12 was delivered by the hemagglutinating virus of Japan (HVJ)-envelope. This vaccine provided remarkable protective efficacy and strong therapeutic efficacy against MDR-TB and XDR-TB in murine models. Furthermore, this vaccine provided therapeutic efficacy of prolongation of survival time of TB infected monkeys and augmented the immune responses. Therefore, the preclinical tests were studied for clinical trial. The injection of 100 μg of the vaccine /mouse i.m. three times in two weeks induced significantly strong production of IFN-γ and IL-2. 100 μg and 200 μg DNA vaccine/mouse i.m. augmented the production of these cytokines compared with 25 μg DNA vaccine/mouse i.m.. The ratio of 100 μg pDNA to 1AU HVJ-E enhanced the production of IFN-γ and IL-2. The decrease in the number of M. tuberculosis in liver of mice was observed by the vaccination of 100μg pDNA. By using these conditions, safety pharmacology study and toxicology test is being studied in monkeys administered by GMP level DNA vaccines. By the toxicology test using monkeys, high dose GMP level vaccine/ monkey is administrated. Safety pharmacological study of repeated administration is also being investigated in GLP level. Furthermore, we have planned to do clinical phase I trial. Targets are human patients with MDR-TB. The safety and tolerability of the vaccine will be evaluated. [Conclusion and recommendations] These data indicate that our novel vaccine might be useful against tuberculosis including XDR-TB and MDR-TB for human therapeutic clinical applications.",,"['Okada, Masaji', 'Kita, Yoko', 'Hashimoto, Satomi', 'Nakatani, Hitoshi', 'Nishimastu, Shiho', 'Kioka, Yumiko', 'Takami, Yasuko']",,,,
,PMC,Postviral Complications: Bacterial Pneumonia,http://dx.doi.org/10.1016/j.ccm.2016.11.006,PMC5324726,,,,,"['Prasso, Jason E.', 'Deng, Jane C.']",,,,
,PMC,Rapid Production of Virus Protein Microarray Using Protein Microarray Fabrication through Gene Synthesis (PAGES),http://dx.doi.org/10.1074/mcp.M116.064873,PMC5294215,,,"The high genetic variability of RNA viruses is a significant factor limiting the discovery of effective biomarkers, the development of vaccines, and characterizations of the immune response during infection. Protein microarrays have been shown to be a powerful method in biomarker discovery and the identification of novel protein–protein interaction networks, suggesting that this technique could also be very useful in studies of infectious RNA viruses. However, to date, the amount of genetic material required to produce protein arrays, as well as the time- and labor-intensive procedures typically needed, have limited their more widespread application. Here, we introduce a method, protein microarray fabrication through gene synthesis (PAGES), for the rapid and efficient construction of protein microarrays particularly for RNA viruses. Using dengue virus as an example, we first identify consensus sequences from 3,604 different strains and then fabricate complete proteomic microarrays that are unique for each consensus sequence. To demonstrate their applicability, we show that these microarrays can differentiate sera from patients infected by dengue virus, related pathogens, or from uninfected patients. We anticipate that the microarray and expression library constructed in this study will find immediate use in further studies of dengue virus and that, more generally, PAGES will become a widely applied method in the clinical characterization of RNA viruses.",,"['Qi, Huan', 'Zhou, Huiqiong', 'Czajkowsky, Daniel Mark', 'Guo, Shujuan', 'Li, Yang', 'Wang, Nan', 'Shi, Yi', 'Lin, Lifeng', 'Wang, Jingfang', 'Wu, De', 'Tao, Sheng-Ce']",,,,
,PMC,"Perspectives on the role of mobility, behavior, and time scales in the spread of diseases",http://dx.doi.org/10.1073/pnas.1604994113,PMC5187743,,,"The dynamics, control, and evolution of communicable and vector-borne diseases are intimately connected to the joint dynamics of epidemiological, behavioral, and mobility processes that operate across multiple spatial, temporal, and organizational scales. The identification of a theoretical explanatory framework that accounts for the pattern regularity exhibited by a large number of host–parasite systems, including those sustained by host–vector epidemiological dynamics, is but one of the challenges facing the coevolving fields of computational, evolutionary, and theoretical epidemiology. Host–parasite epidemiological patterns, including epidemic outbreaks and endemic recurrent dynamics, are characteristic to well-identified regions of the world; the result of processes and constraints such as strain competition, host and vector mobility, and population structure operating over multiple scales in response to recurrent disturbances (like El Niño) and climatological and environmental perturbations over thousands of years. It is therefore important to identify and quantify the processes responsible for observed epidemiological macroscopic patterns: the result of individual interactions in changing social and ecological landscapes. In this perspective, we touch on some of the issues calling for the identification of an encompassing theoretical explanatory framework by identifying some of the limitations of existing theory, in the context of particular epidemiological systems. Fostering the reenergizing of research that aims at disentangling the role of epidemiological and socioeconomic forces on disease dynamics, better understood as complex adaptive systems, is a key aim of this perspective.",,"['Castillo-Chavez, Carlos', 'Bichara, Derdei', 'Morin, Benjamin R.']",,,,
,PMC,A Chemical Biology Solution to Problems with Studying Biologically Important but Unstable 9-O-Acetyl Sialic Acids,http://dx.doi.org/10.1021/acschembio.6b00928,PMC5704959,,,"9-O-Acetylation is a common natural modification on sialic acids (Sias) that terminate many vertebrate glycan chains. This ester group has striking effects on many biological phenomena, including microbe-host interactions, complement action, regulation of immune responses, sialidase action, cellular apoptosis, and tumor immunology. Despite such findings, 9-O-acetyl sialoglycoconjugates have remained largely understudied, primarily because of marked lability of the 9-O-acetyl group to even small pH variations, and/or the action of mammalian or microbial esterases. Our current studies involving 9-O-acetylated sialoglycans on glycan microarrays revealed that even the most careful precautions cannot assure complete stability of the 9-O-acetyl group. We now demonstrate a simple chemical biology solution to many of these problems by substituting the oxygen atom in the ester with a nitrogen atom, resulting in sialic acids with chemically and biologically stable 9-N-acetyl group. We present an efficient one-pot multienzyme method to synthesize a sialoglycan containing 9-acetamido-9-deoxy-N-acetylneuraminic acid (Neu5Ac9NAc) and compare it to the one with naturally occurring 9-O-acetyl-N-acetylneuraminic acid (Neu5,9Ac(2)). Conformational resemblance of the two molecules was confirmed by computational molecular dynamics simulations. Microarray studies showed that the Neu5Ac9NAc-sialoglycan is a ligand for viruses naturally recognizing Neu5,9Ac(2), with a similar affinity but with much improved stability in handling and study. Feeding of Neu5Ac9NAc or Neu5,9Ac(2) to mammalian cells resulted in comparable incorporation and surface expression as well as binding to 9-O-acetyl-Sia-specific viruses. However, cells fed with Neu5Ac9NAc remained resistant to viral esterases and showed a slower turnover. This simple approach opens numerous research opportunities that have heretofore proved intractable.",,"['Khedri, Zahra', 'Xiao, An', 'Yu, Hai', 'Landig, Corinna Susanne', 'Li, Wanqing', 'Diaz, Sandra', 'Wasik, Brian R.', 'Parrish, Colin R.', 'Wang, Lee-Ping', 'Varki, Ajit', 'Chen, Xi']",,,,
,PMC,IRF5 governs liver macrophage activation that promotes hepatic fibrosis in mice and humans,http://dx.doi.org/10.1172/jci.insight.88689,PMC5135279,,,"Hepatic fibrosis arises from inflammation in the liver initiated by resident macrophage activation and massive leukocyte accumulation. Hepatic macrophages hold a central position in maintaining homeostasis in the liver and in the pathogenesis of acute and chronic liver injury linked to fibrogenesis. Interferon regulatory factor 5 (IRF5) has recently emerged as an important proinflammatory transcription factor involved in macrophage activation under acute and chronic inflammation. Here, we revealed that IRF5 is significantly induced in liver macrophages from human subjects developing liver fibrosis from nonalcoholic fatty liver disease or hepatitis C virus infection. Furthermore, IRF5 expression positively correlated with clinical markers of liver damage, such as plasma transaminase and bilirubin levels. Interestingly, mice lacking IRF5 in myeloid cells (MKO) were protected from hepatic fibrosis induced by metabolic or toxic stresses. Transcriptional reprogramming of macrophages lacking IRF5 was characterized by immunosuppressive and antiapoptotic properties. Consequently, IRF5 MKO mice respond to hepatocellular stress by promoting hepatocyte survival, leading to complete protection from hepatic fibrogenesis. Our findings reveal a regulatory network, governed by IRF5, that mediates hepatocyte death and liver fibrosis in mice and humans. Therefore, modulating IRF5 function may be an attractive approach to experimental therapeutics in fibroinflammatory liver disease.",,"['Alzaid, Fawaz', 'Lagadec, Floriane', 'Albuquerque, Miguel', 'Ballaire, Raphaëlle', 'Orliaguet, Lucie', 'Hainault, Isabelle', 'Blugeon, Corinne', 'Lemoine, Sophie', 'Lehuen, Agnès', 'Saliba, David G.', 'Udalova, Irina A.', 'Paradis, Valérie', 'Foufelle, Fabienne', 'Venteclef, Nicolas']",,,,
,PMC,Behavioural interventions to promote workers' use of respiratory protective equipment,http://dx.doi.org/10.1002/14651858.CD010157.pub2,PMC6464013,,,"BACKGROUND: Respiratory hazards are common in the workplace. Depending on the hazard and exposure, the health consequences may include: mild to life‐threatening illnesses from infectious agents, acute effects ranging from respiratory irritation to chronic lung conditions, or even cancer from exposure to chemicals or toxins. Use of respiratory protective equipment (RPE) is an important preventive measure in many occupational settings. RPE only offers protection when worn properly, when removed safely and when it is either replaced or maintained regularly. The effectiveness of behavioural interventions either directed at employers or organisations or directed at individual workers to promote RPE use in workers remains an important unanswered question. OBJECTIVES: To assess the effects of any behavioural intervention either directed at organisations or at individual workers on observed or self‐reported RPE use in workers when compared to no intervention or an alternative intervention. SEARCH METHODS: We searched the Cochrane Work Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 07), MEDLINE (1980 to 12 August 2016), EMBASE (1980 to 20 August 2016) and CINAHL (1980 to 12 August 2016). SELECTION CRITERIA: We included randomised controlled trials (RCTs), controlled before and after (CBA) studies and interrupted time‐series (ITS) comparing behavioural interventions versus no intervention or any other behavioural intervention to promote RPE use in workers. DATA COLLECTION AND ANALYSIS: Four authors independently selected relevant studies, assessed risk of bias and extracted data. We contacted investigators to clarify information. We pooled outcome data from included studies where the studies were sufficiently similar. MAIN RESULTS: We included 14 studies that evaluated the effect of training and education on RPE use, which involved 2052 participants. The included studies had been conducted with farm, healthcare, production line, office and coke oven workers as well as nursing students and people with mixed occupations. All included studies reported the effects of interventions as use of RPE, as correct use of RPE or as indirect measures of RPE use. We did not find any studies where the intervention was delivered and assessed at the whole organization level or in which the main focus was on positive or negative incentives. We rated the quality of the evidence for all comparisons as low to very low. Training versus no training One CBA study in healthcare workers compared training with and without a fit test to no intervention. The study found that the rate of properly fitting respirators was not considerably different in the workers who had received training with a fit test (RR 1.17, 95% Confidence Interval (CI) 0.97 to 1.10) or training without a fit test (RR 1.16, 95% CI 0.95 to 1.42) compared to those who had no training. Two RCTs that evaluated training did not contribute to the analyses because of lack of data. Conventional training plus additions versus conventional training alone One cluster‐randomised trial compared conventional training plus RPE demonstration versus training alone and reported no significant difference in appropriate use of RPE between the two groups (RR 1.41, 95% CI 0.96 to 2.07). One RCT compared interactive training with passive training, with an information screen, and an information book. The mean RPE performance score for the active group was not different from that of the passive group (MD 2.10, 95% CI ‐0.76 to 4.96). However, the active group scored significantly higher than the book group (MD 4.20, 95% CI 0.89 to 7.51) and the screen group (MD 7.00, 95% CI 4.06 to 9.94). One RCT compared computer‐simulation training with conventional personal protective equipment (PPE) training but reported only results for donning and doffing full‐body PPE. Education versus no education One RCT found that a multifaceted educational intervention increased the use of RPE (risk ratio (RR) 1.69, 95% CI 1.10 to 2.58) at three years' follow‐up when compared to no intervention. However, there was no difference between intervention and control at one year's, two years' or four years' follow‐up. Two RCTs did not report enough data to be included in the analysis. Four CBA studies evaluated the effectiveness of education interventions and found no effect on the frequency or correctness of RPE use, except in one study for the use of an N95 mask (RR 4.56, 95% CI 1.84 to 11.33, 1 CBA) in workers. Motivational interviewing versus traditional lectures One CBA study found that participants given motivational group interviewing‐based safety education scored higher on a checklist measuring PPE use (MD 2.95, 95% CI 1.93 to 3.97) than control workers given traditional educational sessions. AUTHORS' CONCLUSIONS: There is very low quality evidence that behavioural interventions, namely education and training, do not have a considerable effect on the frequency or correctness of RPE use in workers. There were no studies on incentives or organisation level interventions. The included studies had methodological limitations and we therefore need further large RCTs with clearer methodology in terms of randomised sequence generation, allocation concealment and assessor blinding, in order to evaluate the effectiveness of behavioural interventions for improving the use of RPE at both organisational and individual levels. In addition, further studies should consider some of the barriers to the successful use of RPE, such as experience of health risk, types of RPE and the employer's attitude to RPE use.",,"['Luong Thanh, Bao Yen', 'Laopaiboon, Malinee', 'Koh, David', 'Sakunkoo, Pornpun', 'Moe, Hla']",,,,
,PMC,Transfer of convalescent serum to pregnant mice prevents Zika virus infection and microcephaly in offspring,http://dx.doi.org/10.1038/cr.2016.144,PMC5223229,,,,,"['Wang, Shuo', 'Hong, Shuai', 'Deng, Yong-Qiang', 'Ye, Qing', 'Zhao, Ling-Zhai', 'Zhang, Fu-Chun', 'Qin, Cheng-Feng', 'Xu, Zhiheng']",,,,
,PMC,"Prevalence of Depression, Depressive Symptoms, and Suicidal Ideation Among Medical Students: A Systematic Review and Meta-Analysis",http://dx.doi.org/10.1001/jama.2016.17324,PMC5613659,,,"IMPORTANCE: Medical students are at high risk for depression and suicidal ideation. However, the prevalence estimates of these disorders vary between studies. OBJECTIVE: To estimate the prevalence of depression, depressive symptoms, and suicidal ideation in medical students. DATA SOURCES AND STUDY SELECTION: Systematic search of EMBASE, ERIC, MEDLINE, psycARTICLES, and psycINFO without language restriction for studies on the prevalence of depression, depressive symptoms, or suicidal ideation in medical students published before September 17, 2016. Studies that were published in the peer-reviewed literature and used validated assessment methods were included. DATA EXTRACTION AND SYNTHESIS: Information on study characteristics; prevalence of depression or depressive symptoms and suicidal ideation; and whether students who screened positive for depression sought treatment was extracted independently by 3 investigators. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were estimated using stratified meta-analysis and meta-regression. MAIN OUTCOMES AND MEASURES: Point or period prevalence of depression, depressive symptoms, or suicidal ideation as assessed by validated questionnaire or structured interview. RESULTS: Depression or depressive symptom prevalence data were extracted from 167 cross-sectional studies (n = 116 628) and 16 longitudinal studies (n = 5728) from 43 countries. All but 1 study used self-report instruments. The overall pooled crude prevalence of depression or depressive symptoms was 27.2% (37 933/122 356 individuals; 95% CI, 24.7% to 29.9%, I(2) = 98.9%). Summary prevalence estimates ranged across assessment modalities from 9.3% to 55.9%. Depressive symptom prevalence remained relatively constant over the period studied (baseline survey year range of 1982–2015; slope, 0.2% increase per year [95% CI, −0.2% to 0.7%]). In the 9 longitudinal studies that assessed depressive symptoms before and during medical school (n = 2432), the median absolute increase in symptoms was 13.5% (range, 0.6% to 35.3%). Prevalence estimates did not significantly differ between studies of only preclinical students and studies of only clinical students (23.7% [95% CI, 19.5% to 28.5%] vs 22.4% [95% CI, 17.6% to 28.2%]; P = .72). The percentage of medical students screening positive for depression who sought psychiatric treatment was 15.7% (110/954 individuals; 95% CI, 10.2% to 23.4%, I(2) = 70.1%). Suicidal ideation prevalence data were extracted from 24 cross-sectional studies (n = 21 002) from 15 countries. All but 1 study used self-report instruments. The overall pooled crude prevalence of suicidal ideation was 11.1% (2043/21 002 individuals; 95% CI, 9.0% to 13.7%, I(2) = 95.8%). Summary prevalence estimates ranged across assessment modalities from 7.4% to 24.2%. CONCLUSIONS AND RELEVANCE: In this systematic review, the summary estimate of the prevalence of depression or depressive symptoms among medical students was 27.2% and that of suicidal ideation was 11.1%. Further research is needed to identify strategies for preventing and treating these disorders in this population.",,"['Rotenstein, Lisa S.', 'Ramos, Marco A.', 'Torre, Matthew', 'Segal, J. Bradley', 'Peluso, Michael J.', 'Guille, Constance', 'Sen, Srijan', 'Mata, Douglas A.']",,,,
,PMC,"Influenza not MERS CoV among returning Hajj and Umrah pilgrims with respiratory illness, Kashmir, north India, 2014–15",http://dx.doi.org/10.1016/j.tmaid.2016.12.002,PMC6057869,,,"BACKGROUND: The increasing reports of Middle East Respiratory Syndrome (MERS) caused by MERS coronavirus (MERS-CoV) from many countries emphasize its importance for international travel. Muslim pilgrimages of Hajj and Umrah involve mass gatherings of international travellers. We set out to assess the presence of influenza and MERS-CoV in Hajj/Umrah returnees with acute respiratory infection. METHODS: Disembarking passengers (n = 8753) from Saudi Arabia (October 2014 to April 2015) were interviewed for the presence of respiratory symptoms; 977 (11%) reported symptoms and 300 (age 26 –90, median 60 years; 140 male) consented to participate in the study. After recording clinical and demographic data, twin swabs (nasopharyngeal and throat) were collected from each participant, pooled in viral transport media and tested by real-time RT PCR for MERS-CoV and influenza A and B viruses and their subtypes. RESULTS: The participants had symptoms of 1–15 days (median 5d); cough (90%) and nasal discharge (86%) being the commonest. None of the 300 participants tested positive for MERS-CoV; however, 33 (11%) tested positive for influenza viruses (A/H3N2 = 13, A/H1N1pdm09 = 9 and B/Yamagata = 11). Eighteen patients received oseltamivir. No hospitalizations were needed and all had uneventful recovery. CONCLUSION: Despite a high prevalence of acute respiratory symptoms, MERS coV was not seen in returning pilgrims from Hajj and Umrah. However detection of flu emphasises preventive strategies like vaccination.",,"['Koul, Parvaiz A.', 'Mir, Hyder', 'Saha, Siddhartha', 'Chadha, Mandeep S.', 'Potdar, Varsha', 'Widdowson, Marc-Alain', 'Lal, Renu B.', 'Krishnan, Anand']",,,,
,PMC,Murine Leukemia Virus (MLV)-based Coronavirus Spike-pseudotyped Particle Production and Infection,http://dx.doi.org/10.21769/BioProtoc.2035,PMC5181643,,,"Viral pseudotyped particles (pp) are enveloped virus particles, typically derived from retroviruses or rhabdoviruses, that harbor heterologous envelope glycoproteins on their surface and a genome lacking essential genes. These synthetic viral particles are safer surrogates of native viruses and acquire the tropism and host entry pathway characteristics governed by the heterologous envelope glycoprotein used. They have proven to be very useful tools used in research with many applications, such as enabling the study of entry pathways of enveloped viruses and to generate effective gene-delivery vectors. The basis for their generation lies in the capacity of some viruses, such as murine leukemia virus (MLV), to incorporate envelope glycoproteins of other viruses into a pseudotyped virus particle. These can be engineered to contain reporter genes such as luciferase, enabling quantification of virus entry events upon pseudotyped particle infection with susceptible cells. Here, we detail a protocol enabling generation of MLV-based pseudotyped particles, using the Middle East respiratory syndrome coronavirus (MERS-CoV) spike (S) as an example of a heterologous envelope glycoprotein to be incorporated. We also describe how these particles are used to infect susceptible cells and to perform a quantitative infectivity readout by a luciferase assay.",,"['Millet, Jean Kaoru', 'Whittaker, Gary R.']",,,,
,PMC,Meeting the Challenge of Epidemic Chikungunya,http://dx.doi.org/10.1093/infdis/jiw291,PMC5137243,,,,,"['Morens, David M.', 'Fauci, Anthony S.']",,,,
,PMC,Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate,http://dx.doi.org/10.1073/pnas.1611408114,PMC5187668,,,"Dendritic cells (DCs) and monocytes develop from a series of bone-marrow–resident progenitors in which lineage potential is regulated by distinct transcription factors. Zeb2 is an E-box–binding protein associated with epithelial–mesenchymal transition and is widely expressed among hematopoietic lineages. Previously, we observed that Zeb2 expression is differentially regulated in progenitors committed to classical DC (cDC) subsets in vivo. Using systems for inducible gene deletion, we uncover a requirement for Zeb2 in the development of Ly-6C(hi) monocytes but not neutrophils, and we show a corresponding requirement for Zeb2 in expression of the M-CSF receptor in the bone marrow. In addition, we confirm a requirement for Zeb2 in development of plasmacytoid DCs but find that Zeb2 is not required for cDC2 development. Instead, Zeb2 may act to repress cDC1 progenitor specification in the context of inflammatory signals.",,"['Wu, Xiaodi', 'Briseño, Carlos G.', 'Grajales-Reyes, Gary E.', 'Haldar, Malay', 'Iwata, Arifumi', 'Kretzer, Nicole M.', 'KC, Wumesh', 'Tussiwand, Roxane', 'Higashi, Yujiro', 'Murphy, Theresa L.', 'Murphy, Kenneth M.']",,,,
,PMC,Angiotensin converting enzyme 2 amplification limited to the circulation does not protect mice from development of diabetic nephropathy,http://dx.doi.org/10.1016/j.kint.2016.09.032,PMC5429993,,,"Blockers of the renin-angiotensin system are effective in the treatment of experimental and clinical diabetic nephropathy. An approach different from blocking the formation or action of angiotensin II(1-8) that could also be effective involves fostering its degradation. Angiotensin converting enzyme 2 (ACE2) is a monocarboxypeptidase than cleaves angiotensin II (1-8) to form angiotensin (1-7). Therefore, we examined the renal effects of murine recombinant ACE2 in mice with streptozotocin-induced diabetic nephropathy as well as that of amplification of circulating ACE2 using minicircle DNA delivery prior to induction of experimental diabetes. This delivery resulted in a long-term sustained and profound increase in serum ACE2 activity and enhanced ability to metabolize an acute angiotensin II (1-8) load. In mice with streptozotocin-induced diabetes pretreated with minicircle ACE2, ACE2 protein in plasma increased markedly and this was associated with a more than 100-fold increase in serum ACE2 activity. However, minicircle ACE2 did not result in changes in urinary ACE2 activity as compared to untreated diabetic mice. In both diabetic groups, glomerular filtration rate increased significantly and to the same extent as compared to non-diabetic controls. Albuminuria, glomerular mesangial expansion, glomerular cellularity and glomerular size, were all increased to a similar extent in minicircle ACE2-treated and untreated diabetic mice, as compared to non-diabetic controls. Recombinant mouse ACE2 given for 4 weeks by intraperitoneal daily injections in mice with streptozotocin-induced diabetic nephropathy also failed to improve albuminuria or kidney pathology. Thus, a profound augmentation of ACE2 confined to the circulation failed to ameliorate the glomerular lesions and hyperfiltration characteristic of early diabetic nephropathy. These findings emphasize the importance of targeting the kidney rather than the circulatory renin angiotensin system to combat diabetic nephropathy.",,"['Wysocki, Jan', 'Ye, Minghao', 'Khattab, Ahmed M.', 'Fogo, Agnes', 'Martin, Aline', 'David, Nicolae Valentin', 'Kanwar, Yashpal', 'Osborn, Mark', 'Batlle, Daniel']",,,,
,PMC,Cytokines IL-17 and IL-22 in the host response to infection,http://dx.doi.org/10.1093/femspd/ftw111,PMC5975231,,,"Cytokines IL-17 and IL-22 play pivotal roles in host defense against microbes and in the development of chronic inflammatory diseases. These cytokines are produced by cells that are often located in epithelial barriers, including subsets of T cells and innate lymphoid cells. In general, IL-17 and IL-22 can be characterized as important cytokines in the rapid response to infectious agents, both by recruiting neutrophils and by inducing the production of antimicrobial peptides. Although each cytokine induces an innate immune response in epithelial cells, their functional spectra are generally distinct: IL-17 mainly induces an inflammatory tissue response and is involved in the pathogenesis of several autoimmune diseases, whereas IL-22 is largely protective and regenerative. In this review, we compare IL-17 and IL-22, describing overlaps and differences in their cellular sources as well as their regulation, signaling, biological functions and roles during disease, with a focus on the contribution of these cytokines to the gut mucosal barrier during bacterial infection.",,"['Valeri, Maria', 'Raffatellu, Manuela']",,,,
,PMC,An effective DNA vaccine platform for Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.21037/atm.2016.11.40,PMC5233508,,,,,"['Cockrell, Adam S.', 'Baric, Ralph S.']",,,,
,PMC,"CFPC welcomes its 2016–2017 President, Dr David White",,PMC5154655,,,,,,,,,
,PMC,"Viruses causing severe acute respiratory infections (SARI) in children ≤5 years of age at a tertiary care hospital in Rajasthan, India",http://dx.doi.org/10.4103/ijmr.IJMR_22_15,PMC5433280,28474624,CC BY-NC-SA,"BACKGROUND & OBJECTIVES: Severe acute respiratory infection (SARI) is one of the leading causes of death among children worldwide. As different respiratory viruses exhibit similar symptoms, simultaneous detection of these viruses in a single reaction mixture can save time and cost. The present study was done in a tertiary care children's hospital for rapid identification of viruses causing SARI among children less than or equal to five years of age using multiplex real-time reverse transcription polymerase chain reaction (RT-PCR) kit. METHODS: A total of 155 throat swabs were collected from equal number of children suspected to have SARI and processed for extraction of nucleic acids using automated extraction system. Multiplex real-time RT-PCR was done to identify the viruses in the samples. RESULTS: The overall positivity for viruses in the study was found to be 72.9 per cent with a co-infection rate of 19.5 per cent. Human metapneumovirus (HMPV) was the predominant virus detected in 25.7 per cent children followed by influenza A (H1N1)pdm09, human rhinovirus (HRV) and human adenovirus (HAdV) in 19.9, 11.0 and 8.8 per cent children, respectively. The HMPV was at its peak in February 2013, HAdV showed two peaks in March-April, 2012 and November 2012-March 2013 while HRV was detected throughout the year. INTERPRETATION & CONCLUSIONS: Multiplex real-time PCR helped in rapid identification of viruses. Seventeen viruses were detected in SARI cases with overall positivity of 72.9 per cent. HMPV was the most predominant virus. However, for better clinico-virological correlation, studies are required with complete work up of all the aetiological agents, clinical profile of patients and treatment outcome.",2016 Dec,"['Malhotra, Bharti', 'Swamy, M. Anjaneya', 'Janardhan Reddy, P. V.', 'Gupta, M. L.']",Indian J Med Res,,,
,PMC,SPEECH INTELLIGIBILITY ASSESSMENT OF PROTECTIVE FACEMASKS AND AIR-PURIFYING RESPIRATORS,http://dx.doi.org/10.1080/15459624.2016.1200723,PMC5065390,,,"Speech Intelligibility (SI) is the perceived quality of sound transmission. In healthcare settings, the ability to communicate clearly with coworkers, patients, etc. is crucial to quality patient care and safety. The objectives of this study were to 1) assess the suitability of the Speech Transmission Index (STI) methods for testing reusable and disposable facial and respiratory personal protective equipment (protective facemasks [PF], N95 filtering facepiece respirators [N95 FFR], and elastomeric half-mask air-purifying respirators [EAPR]) commonly worn by healthcare workers, 2) quantify STI levels of these devices, and 3) contribute to the scientific body of knowledge in the area of SI. SI was assessed using the STI under two experimental conditions: 1) a modified version of the National Fire Protection Association 1981 Supplementary Voice Communications System Performance Test at a Signal to Noise Ratio (SNR) of −15 (66 dBA) and 2) STI measurements utilizing a range of modified pink noise levels (52.5 dBA (−2 SNR) − 72.5 dBA (+7 SNR)) in 5.0 dBA increments. The PF models (Kimberly Clark 49214 and 3M 1818) had the least effect on SI interference, typically deviating from the STI baseline (no-mask condition) by 3% and 4% STI, respectively. The N95FFR (3M 1870, 3M 1860) had more effect on SI interference, typically differing from baseline by 13% and 17%, respectively for models tested. The EAPR models (Scott Xcel and North 5500) had the most significant impact on SI, differing from baseline by 42% for models tested. This data offers insight into the performance of these apparatus with respect to STI and may serve as a reference point for future respirator design considerations, standards development, testing and certification activities.",,"['Palmiero, Andrew J.', 'Symons, Daniel', 'Morgan, Judge W.', 'Shaffer, Ronald E.']",,,,
,PMC,The 2nd World Veterinary Association-World Medical Association Global Conference on One Health(),,PMC5476991,,,,,,,,,
,PMC,Src-independent ERK signaling through the rat α3 isoform of Na/K-ATPase,http://dx.doi.org/10.1152/ajpcell.00199.2016,PMC5401946,,,"The Na/K-ATPase α1 polypeptide supports both ion-pumping and signaling functions. The Na/K-ATPase α3 polypeptide differs from α1 in both its primary structure and its tissue distribution. The expression of α3 seems particularly important in neurons, and recent clinical evidence supports a unique role of this isoform in normal brain function. The nature of this specific role of α3 has remained elusive, because the ubiquitous presence of α1 has hindered efforts to characterize α3-specific functions in mammalian cell systems. Using Na/K-ATPase α1 knockdown pig kidney cells (PY-17), we generated the first stable mammalian cell line expressing a ouabain-resistant form of rat Na/K-ATPase α3 in the absence of endogenous pig α1 detectable by Western blotting. In these cells, Na/K-ATPase α3 formed a functional ion-pumping enzyme and rescued the expression of Na/K-ATPase β1 and caveolin-1 to levels comparable with those observed in PY-17 cells rescued with a rat Na/K-ATPase α1 (AAC-19). The α3-containing enzymes had lower Na(+) affinity and lower ouabain-sensitive transport activity than their α1-containing counterparts under basal conditions, but showed a greater capacity to be activated when intracellular Na(+) was increased. In contrast to Na/K-ATPase α1, α3 could not regulate Src. Upon exposure to ouabain, Src activation did not occur, yet ERK was activated through Src-independent pathways involving PI3K and PKC. Hence, α3 expression confers signaling and pumping properties that are clearly distinct from that of cells expressing Na/K-ATPase α1.",,"['Madan, Namrata', 'Xu, Yunhui', 'Duan, Qiming', 'Banerjee, Moumita', 'Larre, Isabel', 'Pierre, Sandrine V.', 'Xie, Zijian']",,,,
,PMC,Factors determining human-to-human transmissibility of zoonotic pathogens via contact. Human-to-human contact transmission of pathogens,http://dx.doi.org/10.1016/j.coviro.2016.11.004,PMC5346033,,,"The pandemic potential of zoonotic pathogens lies in their ability to become efficiently transmissible amongst humans. Here, we focus on contact-transmitted pathogens and discuss the factors, at the pathogen, host and environmental levels that promote or hinder their human-to-human transmissibility via the following modes of contact transmission: skin contact, sexual contact, respiratory contact and multiple route contact. Factors common to several modes of transmission were immune evasion, high viral load, low infectious dose, crowding, promiscuity, and co-infections; other factors were specific for a pathogen or mode of contact transmission. The identification of such factors will lead to a better understanding of the requirements for human-to-human spread of pathogens, as well as improving risk assessment of newly emerging pathogens.",,"['Richard, Mathilde', 'Knauf, Sascha', 'Lawrence, Philip', 'Mather, Alison E.', 'Munster, Vincent J.', 'Müller, Marcel A.', 'Smith, Derek', 'Kuiken, Thijs']",,,,
,PMC,TMPRSS12 Is an Activating Protease for Subtype B Avian Metapneumovirus,http://dx.doi.org/10.1128/JVI.01567-16,PMC5126379,,,"The entry of avian metapneumovirus (aMPV) into host cells initially requires the fusion of viral and cell membranes, which is exclusively mediated by fusion (F) protein. Proteolysis of aMPV F protein by endogenous proteases of host cells allows F protein to induce membrane fusion; however, these proteases have not been identified. Here, we provide the first evidence that the transmembrane serine protease TMPRSS12 facilitates the cleavage of subtype B aMPV (aMPV/B) F protein. We found that overexpression of TMPRSS12 enhanced aMPV/B F protein cleavage, F protein fusogenicity, and viral replication. Subsequently, knockdown of TMPRSS12 with specific small interfering RNAs (siRNAs) reduced aMPV/B F protein cleavage, F protein fusogenicity, and viral replication. We also found a cleavage motif in the aMPV/B F protein (amino acids 100 and 101) that was recognized by TMPRSS12. The histidine, aspartic acid, and serine residue (HDS) triad of TMPRSS12 was shown to be essential for the proteolysis of aMPV/B F protein via mutation analysis. Notably, we observed TMPRSS12 mRNA expression in target organs of aMPV/B in chickens. Overall, our results indicate that TMPRSS12 is crucial for aMPV/B F protein proteolysis and aMPV/B infectivity and that TMPRSS12 may serve as a target for novel therapeutics and prophylactics for aMPV. IMPORTANCE Proteolysis of the aMPV F protein is a prerequisite for F protein-mediated membrane fusion of virus and cell and for aMPV infection; however, the proteases used in vitro and vivo are not clear. A combination of analyses, including overexpression, knockdown, and mutation methods, demonstrated that the transmembrane serine protease TMPRSS12 facilitated cleavage of subtype B aMPV (aMPV/B) F protein. Importantly, we located the motif in the aMPV/B F protein recognized by TMPRSS12 and the catalytic triad in TMPRSS12 that facilitated proteolysis of the aMPV/B F protein. This is the first report on TMPRSS12 as a protease for proteolysis of viral envelope glycoproteins. Our study will shed light on the mechanism of proteolysis of aMPV F protein and pathogenesis of aMPV.",,"['Yun, Bingling', 'Zhang, Yao', 'Liu, Yongzhen', 'Guan, Xiaolu', 'Wang, Yongqiang', 'Qi, Xiaole', 'Cui, Hongyu', 'Liu, Changjun', 'Zhang, Yanping', 'Gao, Honglei', 'Gao, Li', 'Li, Kai', 'Gao, Yulong', 'Wang, Xiaomei']",,,,
,PMC,Constitutively Expressed IFITM3 Protein in Human Endothelial Cells Poses an Early Infection Block to Human Influenza Viruses,http://dx.doi.org/10.1128/JVI.01254-16,PMC5126373,,,"A role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. We found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses. In HULEC, human influenza viruses were capable of binding to host cellular receptors, becoming internalized and initiating hemifusion but failing to uncoat the viral nucleocapsid and to replicate in host nuclei. Unlike numerous cell types, including epithelial cells, we found that pulmonary endothelial cells constitutively express a high level of the restriction protein IFITM3 in endosomal compartments. IFITM3 knockdown by small interfering RNA (siRNA) could partially rescue H1N1 virus infection in HULEC, suggesting IFITM3 proteins were involved in blocking human influenza virus infection in endothelial cells. In contrast, selected avian influenza viruses were able to escape IFITM3 restriction in endothelial cells, possibly by fusing in early endosomes at higher pH or by other, unknown mechanisms. Collectively, our study demonstrates that the human pulmonary endothelium possesses intrinsic immunity to human influenza viruses, in part due to the constitutive expression of IFITM3 proteins. Notably, certain avian influenza viruses have evolved to escape this restriction, possibly contributing to virus-induced pneumonia and severe lung disease in humans. IMPORTANCE Avian influenza viruses, including H5N1 and H7N9, have been associated with severe respiratory disease and fatal outcomes in humans. Although acute respiratory distress syndrome (ARDS) and progressive pulmonary endothelial damage are known to be present during severe human infections, the role of pulmonary endothelial cells in the pathogenesis of avian influenza virus infections is largely unknown. By comparing human seasonal influenza strains to avian influenza viruses, we provide greater insight into the interaction of influenza virus with human pulmonary endothelial cells. We show that human influenza virus infection is blocked during the early stages of virus entry, which is likely due to the relatively high expression of the host antiviral factors IFITMs (interferon-induced transmembrane proteins) located in membrane-bound compartments inside cells. Overall, this study provides a mechanism by which human endothelial cells limit replication of human influenza virus strains, whereas avian influenza viruses overcome these restriction factors in this cell type.",,"['Sun, Xiangjie', 'Zeng, Hui', 'Kumar, Amrita', 'Belser, Jessica A.', 'Maines, Taronna R.', 'Tumpey, Terrence M.']",,,,
,PMC,The Tetherin Antagonism of the Ebola Virus Glycoprotein Requires an Intact Receptor-Binding Domain and Can Be Blocked by GP1-Specific Antibodies,http://dx.doi.org/10.1128/JVI.01563-16,PMC5126366,,,"The glycoprotein of Ebola virus (EBOV GP), a member of the family Filoviridae, facilitates viral entry into target cells. In addition, EBOV GP antagonizes the antiviral activity of the host cell protein tetherin, which may otherwise restrict EBOV release from infected cells. However, it is unclear how EBOV GP antagonizes tetherin, and it is unknown whether the GP of Lloviu virus (LLOV), a filovirus found in dead bats in Northern Spain, also counteracts tetherin. Here, we show that LLOV GP antagonizes tetherin, indicating that tetherin may not impede LLOV spread in human cells. Moreover, we demonstrate that appropriate processing of N-glycans in tetherin/GP-coexpressing cells is required for tetherin counteraction by EBOV GP. Furthermore, we show that an intact receptor-binding domain (RBD) in the GP1 subunit of EBOV GP is a prerequisite for tetherin counteraction. In contrast, blockade of Niemann-Pick disease type C1 (NPC1), a cellular binding partner of the RBD, did not interfere with tetherin antagonism. Finally, we provide evidence that an antibody directed against GP1, which protects mice from a lethal EBOV challenge, may block GP-dependent tetherin antagonism. Our data, in conjunction with previous reports, indicate that tetherin antagonism is conserved among the GPs of all known filoviruses and demonstrate that the GP1 subunit of EBOV GP plays a central role in tetherin antagonism. IMPORTANCE Filoviruses are reemerging pathogens that constitute a public health threat. Understanding how Ebola virus (EBOV), a highly pathogenic filovirus responsible for the 2013-2016 Ebola virus disease epidemic in western Africa, counteracts antiviral effectors of the innate immune system might help to define novel targets for antiviral intervention. Similarly, determining whether Lloviu virus (LLOV), a filovirus detected in bats in northern Spain, is inhibited by innate antiviral effectors in human cells might help to determine whether the virus constitutes a threat to humans. The present study shows that LLOV, like EBOV, counteracts the antiviral effector protein tetherin via its glycoprotein (GP), suggesting that tetherin does not pose a defense against LLOV spread in humans. Moreover, our work identifies the GP1 subunit of EBOV GP, in particular an intact receptor-binding domain, as critical for tetherin counteraction and provides evidence that antibodies directed against GP1 can interfere with tetherin counteraction.",,"['Brinkmann, Constantin', 'Nehlmeier, Inga', 'Walendy-Gnirß, Kerstin', 'Nehls, Julia', 'González Hernández, Mariana', 'Hoffmann, Markus', 'Qiu, Xiangguo', 'Takada, Ayato', 'Schindler, Michael', 'Pöhlmann, Stefan']",,,,
,PMC,A Mouse Model for MERS Coronavirus Induced Acute Respiratory Distress Syndrome,http://dx.doi.org/10.1038/nmicrobiol.2016.226,PMC5578707,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe pneumonia-like symptoms, and multi-organ failure, with a case fatality rate of ~36%. Limited clinical studies indicate that humans infected with MERS-CoV exhibited pathology consistent with late stages of ARDS, which is reminiscent of disease observed in patients infected with SARS coronavirus. Models of MERS-CoV-induced severe respiratory disease have been difficult to achieve, and small animal models traditionally used to investigate viral pathogenesis (mouse, hamster, guinea pig, and ferret) are naturally resistant to MERS-CoV. Therefore, we used CRISPR/Cas9 to modify the mouse genome to encode two human amino acids (288 and 330) in the dipeptidyl peptidase 4 receptor, making mice susceptible to MERS-CoV replication. Serial MERS-CoV passage in these engineered mice was then used to generate a mouse-adapted virus that replicated efficiently within the lungs, and evoked symptoms indicative of severe acute respiratory distress syndrome (ARDS), including decreased survival, extreme weight loss, decreased pulmonary function, pulmonary hemorrhage, and pathological signs indicative of end stage lung disease. Importantly, therapeutic countermeasures comprising MERS-CoV neutralizing antibody treatment or a MERS-CoV spike protein vaccine protected engineered mice against MERS-CoV-induced ARDS.",,"['Cockrell, Adam S.', 'Yount, Boyd L.', 'Scobey, Trevor', 'Jensen, Kara', 'Douglas, Madeline', 'Beall, Anne', 'Tang, Xian-Chun', 'Marasco, Wayne A.', 'Heise, Mark T.', 'Baric, Ralph S.']",,,,
,PMC,Development of a microbial dose response visualization and modelling application for QMRA modelers and educators,http://dx.doi.org/10.1016/j.envsoft.2016.11.011,PMC5665384,,,"Microbial dose response modelling is vital to a well-characterized microbial risk estimate. Dose response modelling is an inherently multidisciplinary field, which collates knowledge and data from disparate scientific fields. This multidisciplinary nature presents a key challenge to the expansion of microbial dose response modelling into new groups of researchers and modelers. This research employs a dose response optimization R code used in 18 peer-reviewed research studies to develop a multi-functional dose response software. The underlying R code performs an optimization of the two primary dose response models using the MLE method and outputs statistical analyses of the fits and bootstrapped uncertainty information for the models. VizDR (Visual Dose Response) was developed to provide microbial dose response modelling capabilities to a larger audience. VizDR is programmed in JavaScript with underlying Python scripts for intercommunication with Rserve. VizDR allows for dose response model visualization and optimization of a user's own experimental data.",,"['Weir, Mark H.', 'Mitchell, Jade', 'Flynn, William', 'Pope, Joanna M.']",,,,
,PMC,Middle East Respiratory Syndrome Coronavirus and Children: What Pediatric Health Care Professionals Need to Know,http://dx.doi.org/10.1177/0009922816678820,PMC5288265,,,,,"['Bartenfeld, Michael', 'Griese, Stephanie', 'Uyeki, Timothy', 'Gerber, Susan I.', 'Peacock, Georgina']",,,,
,PMC,Clinical Utility of On-Demand Multiplex Respiratory Pathogen Testing among Adult Outpatients,http://dx.doi.org/10.1128/JCM.01579-16,PMC5121384,,,"Multiplex tests for respiratory tract infections include up to 20 targets for common pathogens, predominantly viruses. A specific therapeutic intervention is available for individuals testing positive for influenza viruses (oseltamivir), and it is potentially beneficial to identify non-influenza viruses to avoid unnecessary antibiotic use. We evaluated antimicrobial prescriptions following respiratory pathogen testing among outpatients at a large Veterans Administration (VA) medical center. Results of the FilmArray respiratory panel (BioFire, Salt Lake City, UT) from 15 December 2014 to 15 April 2015 were evaluated among 408 outpatients, and patient medical records were reviewed. Differences in antibiotic and oseltamivir prescription rates were analyzed. Among 408 patients tested in outpatient centers (emergency departments, urgent care clinics, and outpatient clinics), 295 (72.3%) were managed as outpatients. Among these 295 outpatients, 105 (35.6%) tested positive for influenza virus, 109 (36.9%) tested positive for a non-influenza virus pathogen, and 81 (27.5%) had no respiratory pathogen detected. Rates of oseltamivir and antibiotic prescriptions were significantly different among the three test groups (chi-squared values of 167.6 [P < 0.0001] and 10.48 [P = 0.005], respectively), but there was no significant difference in antibiotic prescription rates between the non-influenza virus pathogen group and those who tested negative (chi-square value, 0; P = 1.0). Among adult outpatients, testing positive for influenza virus was associated with receiving fewer antibiotic prescriptions, but no such effect was seen for those who tested positive for a non-influenza virus. These data suggest that testing for influenza viruses alone may be sufficient and more cost-effective than multiplex pathogen testing for outpatients.",,"['Green, Daniel A.', 'Hitoaliaj, Letiana', 'Kotansky, Brian', 'Campbell, Sheldon M.', 'Peaper, David R.']",,,,
,PMC,Comparison of NxTAG Respiratory Pathogen Panel and Anyplex II RV16 Tests for Multiplex Detection of Respiratory Pathogens in Hospitalized Children,http://dx.doi.org/10.1128/JCM.01243-16,PMC5121377,,,"Multiplex molecular techniques can detect a diversity of respiratory viruses and bacteria that cause childhood acute respiratory infection rapidly and conveniently. However, currently available techniques show high variation in performance. We sought to compare the diagnostic accuracy of the novel multiplex NxTAG respiratory pathogen panel (RPP) RUO test versus a routine multiplex Anyplex II RV16 assay in respiratory specimens collected from children <18 years of age hospitalized with nonspecific symptoms of acute lower respiratory infection. Parallel testing was performed on nasopharyngeal aspirates prospectively collected at referral Children's Hospital Sant Joan de Déu (Barcelona, Spain) between June and November 2015. Agreement values between the two tests and kappa coefficients were assessed. Bidirectional sequencing was performed for the resolution of discordant results. A total of 319 samples were analyzed by both techniques. A total of 268 (84.0%) of them yielded concordant results. Positive percent agreement values ranged from 83.3 to 100%, while the negative percent agreement was more than 99% for all targets except for enterovirus/rhinovirus (EV/RV; 94.4%). Kappa coefficients ranged from 0.83 to 1.00. Discrepancy analysis confirmed 66.0% of NxTAG RPP RUO results. A total of 260 viruses were detected, with EV/RV (n = 105, 40.4%) being the most prevalent target. Viral coinfections were found in 44 (14.2%) samples. In addition, NxTAG RPP RUO detected single bacterial and mixed viral-bacterial infections in seven samples. NxTAG RPP RUO showed high positive and negative agreement with Anyplex II RV16 for main viruses that cause acute respiratory infections in children, coupled with an additional capability to detect some respiratory bacteria.",,"['Brotons, Pedro', 'Henares, Desiree', 'Latorre, Irene', 'Cepillo, Antonio', 'Launes, Cristian', 'Muñoz-Almagro, Carmen']",,,,
,PMC,Photoantimicrobials—are we afraid of the light?,http://dx.doi.org/10.1016/S1473-3099(16)30268-7,PMC5280084,,,"Although conventional antimicrobial drugs have been viewed as miraculous cure-alls for the past 80 years, increasing antimicrobial drug resistance requires a major and rapid intervention. However, the development of novel but still conventional systemic antimicrobial agents, having only a single mode or site of action, will not alleviate the situation because it is probably only a matter of time until any such agents will also become ineffective. To continue to produce new agents based on this notion is unacceptable, and there is an increasing need for alternative approaches to the problem. By contrast, light-activated molecules called photoantimicrobials act locally via the in-situ production of highly reactive oxygen species, which simultaneously attack various biomolecular sites in the pathogenic target and therefore offer both multiple and variable sites of action. This non-specificity at the target circumvents conventional mechanisms of resistance and inhibits the development of resistance to the agents themselves. Photoantimicrobial therapy is safe and easy to implement and, unlike conventional agents, the activity spectrum of photoantimicrobials covers bacteria, fungi, viruses, and protozoa. However, clinical trials of these new, truly broad-spectrum, and minimally toxic agents have been few, and the funding for research and development is almost non-existent. Photoantimicrobials constitute one of the few ways forward through the morass of drug-resistant infectious disease and should be fully explored. In this Personal View, we raise awareness of the novel photoantimicrobial technologies that offer a viable alternative to conventional drugs in many relevant application fields, and could thus slow the pace of resistance development.",,"['Wainwright, Mark', 'Maisch, Tim', 'Nonell, Santi', 'Plaetzer, Kristjan', 'Almeida, Adelaide', 'Tegos, George P', 'Hamblin, Michael R']",,,,
,PMC,Phosphate-binding pocket in Dicer-2 PAZ domain for high-fidelity siRNA production,http://dx.doi.org/10.1073/pnas.1612393113,PMC5150366,,,"The enzyme Dicer produces small silencing RNAs such as micro-RNAs (miRNAs) and small interfering RNAs (siRNAs). In Drosophila, Dicer-1 produces ∼22–24-nt miRNAs from pre-miRNAs, whereas Dicer-2 makes 21-nt siRNAs from long double-stranded RNAs (dsRNAs). How Dicer-2 precisely makes 21-nt siRNAs with a remarkably high fidelity is unknown. Here we report that recognition of the 5′-monophosphate of a long dsRNA substrate by a phosphate-binding pocket in the Dicer-2 PAZ (Piwi, Argonaute, and Zwille/Pinhead) domain is crucial for the length fidelity, but not the efficiency, in 21-nt siRNA production. Loss of the length fidelity, meaning increased length heterogeneity of siRNAs, caused by point mutations in the phosphate-binding pocket of the Dicer-2 PAZ domain decreased RNA silencing activity in vivo, showing the importance of the high fidelity to make 21-nt siRNAs. We propose that the 5′-monophosphate of a long dsRNA substrate is anchored by the phosphate-binding pocket in the Dicer-2 PAZ domain and the distance between the pocket and the RNA cleavage active site in the RNaseIII domain corresponds to the 21-nt pitch in the A-form duplex of a long dsRNA substrate, resulting in high-fidelity 21-nt siRNA production. This study sheds light on the molecular mechanism by which Dicer-2 produces 21-nt siRNAs with a remarkably high fidelity for efficient RNA silencing.",,"['Kandasamy, Suresh K.', 'Fukunaga, Ryuya']",,,,
,PMC,"Innate Immunity, Hemostasis and Matrix Remodeling: PTX3 as a Link",http://dx.doi.org/10.1016/j.smim.2016.10.012,PMC5414833,,,"Innate immunity is evolutionarily connected with hemostasis. PTX3 is an essential fluid-phase pattern recognition molecule of the innate immune system that acts as a functional ancestor of antibodies. PTX3 by interacting with defense collagens and fibrinogens amplifies effector functions of the innate immune system. At wound sites, PTX3 regulates the injury-induced thrombotic response and promotes wound healing by favoring timely fibrinolysis. Therefore, PTX3 interacts with ancestral domains conserved in innate immunity, hemostasis and extracellular matrix and exerts functions related to both antimicrobial resistance and tissue repair. These findings strengthen the connection between innate immune system and hemostasis, and suggest that recognition of microbes and extracellular matrix are evolutionarily conserved and integrated functions of the innate immune system.",,"['Doni, Andrea', 'Garlanda, Cecilia', 'Mantovani, Alberto']",,,,
,PMC,"THE EMERGENCE OF ARTHROPOD-BORNE VIRAL DISEASES: A GLOBAL PROSPECTIVE ON DENGUE, CHIKUNGUNYA AND ZIKA FEVERS",http://dx.doi.org/10.1016/j.actatropica.2016.11.020,PMC5203945,,,"Arthropod-borne viruses (arboviruses) present a substantial threat to human and animal health worldwide. Arboviruses can cause a variety of clinical presentations that range from mild to life threatening symptoms. Many arboviruses are present in nature through two distinct cycles, the urban and sylvatic cycle that are maintained in complex biological cycles. In this review we briefly discuss the factors driving the emergence of arboviruses, such as the anthropogenic aspects of unrestrained human population growth, economic expansion and globalization. Also the important aspects of viruses and vectors in the occurrence of arboviruses epidemics. The focus of this review will be on dengue, zika and chikungunya viruses, particularly because these viruses are currently causing a negative impact on public health and economic damage around the world.",,"['Mayer, Sandra V.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",,,,
,PMC,RasIns: Genetically Encoded Intrabodies of Activated Ras Proteins,http://dx.doi.org/10.1016/j.jmb.2016.11.008,PMC5798998,,,"K- and H-Ras are the most commonly mutated genes in human tumors and are critical for conferring and maintaining the oncogenic phenotype in tumors with poor prognoses. Here, we design genetically encoded antibody-like ligands (intrabodies) that recognize active, GTP-bound K- and H-Ras. These ligands, which use the 10th domain of human fibronectin as their scaffold, are stable inside the cells and when fused with a fluorescent protein label, the constitutively active G12V mutant H-Ras. Primary selection of ligands against Ras with mRNA display resulted in an intrabody (termed RasIn1) that binds with a K(D) of 2.1 μM to H-Ras(G12V) (GTP), excellent state selectivity, and remarkable specificity for K- and H-Ras. RasIn1 recognizes residues in the Switch I region of Ras, similar to Raf-RBD, and competes with Raf-RBD for binding. An affinity maturation selection based on RasIn1 resulted in RasIn2, which binds with a K(D) of 120 nM and also retains excellent state selectivity. Both of these intrabodies colocalize with H-Ras, K-Ras, and G12V mutants inside the cells, providing new potential tools to monitor and modulate Ras-mediated signaling. Finally, RasIn1 and Rasin2 both display selectivity for the G12V mutants as compared with wild-type Ras providing a potential route for mutant selective recognition of Ras.",,"['Cetin, Mehmet', 'Evenson, William E.', 'Gross, Garrett G.', 'Jalali-Yazdi, Farzad', 'Krieger, Daniel', 'Arnold, Don', 'Takahashi, Terry T.', 'Roberts, Richard W.']",,,,
,PMC,Sizes of Long RNA Molecules Are Determined by the Branching Patterns of Their Secondary Structures,http://dx.doi.org/10.1016/j.bpj.2016.10.014,PMC5113152,,,"Long RNA molecules are at the core of gene regulation across all kingdoms of life, while also serving as genomes in RNA viruses. Few studies have addressed the basic physical properties of long single-stranded RNAs. Long RNAs with nonrepeating sequences usually adopt highly ramified secondary structures and are better described as branched polymers. To test whether a branched polymer model can estimate the overall sizes of large RNAs, we employed fluorescence correlation spectroscopy to examine the hydrodynamic radii of a broad spectrum of biologically important RNAs, ranging from viral genomes to long noncoding regulatory RNAs. The relative sizes of long RNAs measured at low ionic strength correspond well to those predicted by two theoretical approaches that treat the effective branching associated with secondary structure formation—one employing the Kramers theorem for calculating radii of gyration, and the other featuring the metric of maximum ladder distance. Upon addition of multivalent cations, most RNAs are found to be compacted as compared with their original, low ionic-strength sizes. These results suggest that sizes of long RNA molecules are determined by the branching pattern of their secondary structures. We also experimentally validate the proposed computational approaches for estimating hydrodynamic radii of single-stranded RNAs, which use generic RNA structure prediction tools and thus can be universally applied to a wide range of long RNAs.",,"['Borodavka, Alexander', 'Singaram, Surendra\xa0W.', 'Stockley, Peter\xa0G.', 'Gelbart, William\xa0M.', 'Ben-Shaul, Avinoam', 'Tuma, Roman']",,,,
,PMC,Post-translational Control of Intracellular Pathogen Sensing Pathways,http://dx.doi.org/10.1016/j.it.2016.10.008,PMC5580928,,,"Mammalian cells recognize virus-derived nucleic acids using a defined set of intracellular sensors including the DNA sensors cyclic GMP–AMP (cGAMP) synthase (cGAS) and interferon gamma (IFNγ)-inducible protein 16 (IFI16) as well as viral RNA receptors of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family. Following innate immune recognition, these sensors launch an immune response that is characterized by the transcriptional upregulation of many antiviral molecules, including proinflammatory cytokines, chemokines, and IFN-stimulated genes. Recent studies have demonstrated that the signal transduction initiated by these sensors is sophisticatedly regulated by post-translational modifications (PTMs) resulting in a robust yet ‘tunable’ cytokine response to maintain immune homeostasis. Here we summarize recent advances in our understanding of how PTMs and regulatory enzymes control the signaling activity of RLRs, cGAS, and IFI16 as well as their proximal adaptor proteins.",,"['Chiang, Cindy', 'Gack, Michaela U.']",,,,
,PMC,Rheum emodin inhibits enterovirus 71 viral replication and affects the host cell cycle environment,http://dx.doi.org/10.1038/aps.2016.110,PMC5342659,,,"Human enterovirus 71 (EV71) is the primary causative agent of recent large-scale outbreaks of hand, foot, and mouth disease (HFMD) in Asia. Currently, there are no drugs available for the prevention and treatment of HFMD. In this study, we compared the anti-EV71 activities of three natural compounds, rheum emodin, artemisinin and astragaloside extracted from Chinese herbs Chinese rhubarb, Artemisia carvifolia and Astragalus, respectively, which have been traditionally used for the treatment and prevention of epidemic diseases. Human lung fibroblast cell line MRC5 was mock-infected or infected with EV71, and treated with drugs. The cytotoxicity of the drugs was detected with MTT assay. The cytopathic effects such as cell death and condensed nuclei were morphologically observed. The VP1-coding sequence required for EV71 genome replication was assayed with qRT-PCR. Viral protein expression was analyzed with Western blotting. Viral TCID50 was determined to evaluate EV71 virulence. Flow cytometry analysis of propidium iodide staining was performed to analyze the cell cycle distribution of MRC5 cells. Rheum emodin (29.6 μmol/L) effectively protected MRC5 cells from EV71-induced cytopathic effects, which resulted from the inhibiting viral replication: rheum emodin treatment decreased viral genomic levels by 5.34-fold, viral protein expression by less than 30-fold and EV71 virulence by 0.33107-fold. The fact that inhibition of rheum emodin on viral virulence was much stronger than its effects on genomic levels and viral protein expression suggested that rheum emodin inhibited viral maturation. Furthermore, rheum emodin treatment markedly diminished cell cycle arrest at S phase in MRC5 cells, which was induced by EV71 infection and favored the viral replication. In contrast, neither astragaloside (50 μmol/L) nor artemisinin (50 μmol/L) showed similar anti-EV71 activities. Among the three natural compounds tested, rheum emodin effectively suppressed EV71 viral replication, thus is a candidate anti-HFMD drug.",,"['Zhong, Ting', 'Zhang, Li-ying', 'Wang, Zeng-yan', 'Wang, Yue', 'Song, Feng-mei', 'Zhang, Ya-hong', 'Yu, Jing-hua']",,,,
,PMC,Structure-Based Exploration and Exploitation of the S(4) Subsite of Norovirus 3CL Protease in the Design of Potent and Permeable Inhibitors,http://dx.doi.org/10.1016/j.ejmech.2016.11.027,PMC5501333,,,"Human noroviruses are the primary cause of epidemic and sporadic acute gastroenteritis. The worldwide high morbidity and mortality associated with norovirus infections, particularly among the elderly, immunocompromised patients and children, constitute a serious public health concern. There are currently no approved human vaccines or norovirus-specific small-molecule therapeutics or prophylactics. Norovirus 3CL protease has recently emerged as a potential therapeutic target for the development of anti-norovirus agents. We hypothesized that the S(4) subsite of the enzyme may provide an effective means of designing potent and cell permeable inhibitors of the enzyme. We report herein the structure-guided exploration and exploitation of the S(4) subsite of norovirus 3CL protease in the design and synthesis of effective inhibitors of the protease.",,"['Galasiti Kankanamalage, Anushka C.', 'Kim, Yunjeong', 'Rathnayake, Athri D.', 'Damalanka, Vishnu C.', 'Weerawarna, Pathum M.', 'Doyle, Sean T.', 'Alsoudi, Amer F.', 'Padmasankha Dissanayake, D. M.', 'Lushington, Gerald H.', 'Mehzabeen, Nurjahan', 'Battaile, Kevin P.', 'Lovell, Scott', 'Chang, Kyeong-Ok', 'Groutas, William C.']",,,,
,PMC,Big Data for Infectious Disease Surveillance and Modeling,http://dx.doi.org/10.1093/infdis/jiw400,PMC5181547,,,"We devote a special issue of the Journal of Infectious Diseases to review the recent advances of big data in strengthening disease surveillance, monitoring medical adverse events, informing transmission models, and tracking patient sentiments and mobility. We consider a broad definition of big data for public health, one encompassing patient information gathered from high-volume electronic health records and participatory surveillance systems, as well as mining of digital traces such as social media, Internet searches, and cell-phone logs. We introduce nine independent contributions to this special issue and highlight several cross-cutting areas that require further research, including representativeness, biases, volatility, and validation, and the need for robust statistical and hypotheses-driven analyses. Overall, we are optimistic that the big-data revolution will vastly improve the granularity and timeliness of available epidemiological information, with hybrid systems augmenting rather than supplanting traditional surveillance systems, and better prospects for accurate infectious diseases models and forecasts.",,"['Bansal, Shweta', 'Chowell, Gerardo', 'Simonsen, Lone', 'Vespignani, Alessandro', 'Viboud, Cécile']",,,,
,PMC,Elucidating Transmission Patterns From Internet Reports: Ebola and Middle East Respiratory Syndrome as Case Studies,http://dx.doi.org/10.1093/infdis/jiw356,PMC5144900,,,"The paucity of traditional epidemiological data during epidemic emergencies calls for alternative data streams to characterize the key features of an outbreak, including the nature of risky exposures, the reproduction number, and transmission heterogeneities. We illustrate the potential of Internet data streams to improve preparedness and response in outbreak situations by drawing from recent work on the 2014–2015 Ebola epidemic in West Africa and the 2015 Middle East respiratory syndrome (MERS) outbreak in South Korea. We show that Internet reports providing detailed accounts of epidemiological clusters are particularly useful to characterize time trends in the reproduction number. Moreover, exposure patterns based on Internet reports align with those derived from epidemiological surveillance data on MERS and Ebola, underscoring the importance of disease amplification in hospitals and during funeral rituals (associated with Ebola), prior to the implementation of control interventions. Finally, we discuss future developments needed to generalize Internet-based approaches to study transmission dynamics.",,"['Chowell, Gerardo', 'Cleaton, Julie M.', 'Viboud, Cecile']",,,,
,PMC,A Novel Benzodiazepine Compound Inhibits Yellow Fever Virus Infection by Specifically Targeting NS4B Protein,http://dx.doi.org/10.1128/JVI.01253-16,PMC5110185,,,"Although a highly effective vaccine is available, the number of yellow fever cases has increased over the past 2 decades, which highlights the pressing need for antiviral therapeutics. In a high-throughput screening campaign, we identified an acetic acid benzodiazepine (BDAA) compound which potently inhibits yellow fever virus (YFV). Interestingly, while treatment of YFV-infected cultures with 2 μM BDAA reduced the virion production by greater than 2 logs, the compound was not active against 21 other viruses from 14 different viral families. Selection and genetic analysis of drug-resistant viruses revealed that replacement of the proline at amino acid 219 (P219) of the nonstructural protein 4B (NS4B) with serine, threonine, or alanine conferred YFV with resistance to BDAA without apparent loss of replication fitness in cultured mammalian cells. However, replacement of P219 with glycine conferred BDAA resistance with significant loss of replication ability. Bioinformatics analysis predicts that the P219 amino acid is localized at the endoplasmic reticulum lumen side of the fifth putative transmembrane domain of NS4B, and the mutation may render the viral protein incapable of interacting with BDAA. Our studies thus revealed an important role and the structural basis for the NS4B protein in supporting YFV replication. Moreover, in YFV-infected hamsters, oral administration of BDAA protected 90% of the animals from death, significantly reduced viral load by greater than 2 logs, and attenuated virus infection-induced liver injury and body weight loss. The encouraging preclinical results thus warrant further development of BDAA or its derivatives as antiviral agents to treat yellow fever. IMPORTANCE Yellow fever is an acute viral hemorrhagic disease which threatens approximately 1 billion people living in tropical areas of Africa and Latin America. Although a highly effective yellow fever vaccine has been available for more than 7 decades, the low vaccination rate fails to prevent outbreaks in at-risk regions. It has been estimated that up to 1.7 million YFV infections occur in Africa each year, resulting in 29,000 to 60,000 deaths. Thus far, there is no specific antiviral treatment for yellow fever. To cope with this medical challenge, we identified a benzodiazepine compound that selectively inhibits YFV by targeting the viral NS4B protein. To our knowledge, this is the first report demonstrating in vivo safety and antiviral efficacy of a YFV NS4B inhibitor in an animal model. We have thus reached a critical milestone toward the development of specific antiviral therapeutics for clinical management of yellow fever.",,"['Guo, Fang', 'Wu, Shuo', 'Julander, Justin', 'Ma, Julia', 'Zhang, Xuexiang', 'Kulp, John', 'Cuconati, Andrea', 'Block, Timothy M.', 'Du, Yanming', 'Guo, Ju-Tao', 'Chang, Jinhong']",,,,
,PMC,Convallatoxin-Induced Reduction of Methionine Import Effectively Inhibits Human Cytomegalovirus Infection and Replication,http://dx.doi.org/10.1128/JVI.01050-16,PMC5110156,,,"Cytomegalovirus (CMV) is a ubiquitous human pathogen that increases the morbidity and mortality of immunocompromised individuals. The current FDA-approved treatments for CMV infection are intended to be virus specific, yet they have significant adverse side effects, including nephrotoxicity and hematological toxicity. Thus, there is a medical need for safer and more effective CMV therapeutics. Using a high-content screen, we identified the cardiac glycoside convallatoxin as an effective compound that inhibits CMV infection. Using a panel of cardiac glycoside variants, we assessed the structural elements critical for anti-CMV activity by both experimental and in silico methods. Analysis of the antiviral effects, toxicities, and pharmacodynamics of different variants of cardiac glycosides identified the mechanism of inhibition as reduction of methionine import, leading to decreased immediate-early gene translation without significant toxicity. Also, convallatoxin was found to dramatically reduce the proliferation of clinical CMV strains, implying that its mechanism of action is an effective strategy to block CMV dissemination. Our study has uncovered the mechanism and structural elements of convallatoxin, which are important for effectively inhibiting CMV infection by targeting the expression of immediate-early genes. IMPORTANCE Cytomegalovirus is a highly prevalent virus capable of causing severe disease in certain populations. The current FDA-approved therapeutics all target the same stage of the viral life cycle and induce toxicity and viral resistance. We identified convallatoxin, a novel cell-targeting antiviral that inhibits CMV infection by decreasing the synthesis of viral proteins. At doses low enough for cells to tolerate, convallatoxin was able to inhibit primary isolates of CMV, including those resistant to the anti-CMV drug ganciclovir. In addition to identifying convallatoxin as a novel antiviral, limiting mRNA translation has a dramatic impact on CMV infection and proliferation.",,"['Cohen, Tobias', 'Williams, John D.', 'Opperman, Timothy J.', 'Sanchez, Roberto', 'Lurain, Nell S.', 'Tortorella, Domenico']",,,,
,PMC,Hepacivirus NS3/4A Proteases Interfere with MAVS Signaling in both Their Cognate Animal Hosts and Humans: Implications for Zoonotic Transmission,http://dx.doi.org/10.1128/JVI.01634-16,PMC5110154,,,"Multiple novel members of the genus Hepacivirus have recently been discovered in diverse mammalian species. However, to date, their replication mechanisms and zoonotic potential have not been explored in detail. The NS3/4A serine protease of hepatitis C virus (HCV) is critical for cleavage of the viral polyprotein. It also cleaves the cellular innate immune adaptor MAVS, thus decreasing interferon (IFN) production and contributing to HCV persistence in the human host. To investigate the conservation of fundamental aspects of the hepaciviral life cycle, we explored if MAVS cleavage and suppression of innate immune signaling represent a common mechanism employed across different clades of the genus Hepacivirus to enhance viral replication. To estimate the zoonotic potential of these nonhuman hepaciviruses, we assessed if their NS3/4A proteases were capable of cleaving human MAVS. NS3/4A proteases of viruses infecting colobus monkeys, rodents, horses, and cows cleaved the MAVS proteins of their cognate hosts and interfered with the ability of MAVS to induce the IFN-β promoter. All NS3/4A proteases from nonhuman viruses readily cleaved human MAVS. Thus, NS3/4A-dependent cleavage of MAVS is a conserved replication strategy across multiple clades within the genus Hepacivirus. Human MAVS is susceptible to cleavage by these nonhuman viral proteases, indicating that it does not pose a barrier for zoonotic transmission of these viruses to humans. IMPORTANCE Virus infection is recognized by cellular sensor proteins triggering innate immune signaling and antiviral defenses. While viruses have evolved strategies to thwart these antiviral programs in their cognate host species, these evasion mechanisms are often ineffective in a novel host, thus limiting viral transmission across species. HCV, the best-characterized member of the genus Hepacivirus within the family Flaviviridae, uses its NS3/4A protease to disrupt innate immune signaling by cleaving the cellular adaptor protein MAVS. Recently, a large number of HCV-related viruses have been discovered in various animal species, including wild, livestock, and companion animals. We show that the NS3/4A proteases of these hepaciviruses from different animals and representing various clades of the genus cleave their cognate host MAVS proteins in addition to human MAVS. Therefore, cleavage of MAVS is a common strategy of hepaciviruses, and human MAVS is likely unable to limit replication of these nonhuman viruses upon zoonotic exposure.",,"['Anggakusuma,', 'Brown, Richard J. P.', 'Banda, Dominic H.', 'Todt, Daniel', 'Vieyres, Gabrielle', 'Steinmann, Eike', 'Pietschmann, Thomas']",,,,
,PMC,Mapping membrane activity in undiscovered peptide sequence space using machine learning,http://dx.doi.org/10.1073/pnas.1609893113,PMC5137689,,,"There are some ∼1,100 known antimicrobial peptides (AMPs), which permeabilize microbial membranes but have diverse sequences. Here, we develop a support vector machine (SVM)-based classifier to investigate ⍺-helical AMPs and the interrelated nature of their functional commonality and sequence homology. SVM is used to search the undiscovered peptide sequence space and identify Pareto-optimal candidates that simultaneously maximize the distance σ from the SVM hyperplane (thus maximize its “antimicrobialness”) and its ⍺-helicity, but minimize mutational distance to known AMPs. By calibrating SVM machine learning results with killing assays and small-angle X-ray scattering (SAXS), we find that the SVM metric σ correlates not with a peptide’s minimum inhibitory concentration (MIC), but rather its ability to generate negative Gaussian membrane curvature. This surprising result provides a topological basis for membrane activity common to AMPs. Moreover, we highlight an important distinction between the maximal recognizability of a sequence to a trained AMP classifier (its ability to generate membrane curvature) and its maximal antimicrobial efficacy. As mutational distances are increased from known AMPs, we find AMP-like sequences that are increasingly difficult for nature to discover via simple mutation. Using the sequence map as a discovery tool, we find a unexpectedly diverse taxonomy of sequences that are just as membrane-active as known AMPs, but with a broad range of primary functions distinct from AMP functions, including endogenous neuropeptides, viral fusion proteins, topogenic peptides, and amyloids. The SVM classifier is useful as a general detector of membrane activity in peptide sequences.",,"['Lee, Ernest Y.', 'Fulan, Benjamin M.', 'Wong, Gerard C. L.', 'Ferguson, Andrew L.']",,,,
,PMC,Sequence-specific Sensing of Nucleic Acids,http://dx.doi.org/10.1016/j.it.2016.10.006,PMC5205569,,,"Innate immune cells are endowed with many nucleic acid receptors, but the role of sequence in the detection of foreign organisms remains unclear. Can sequence patterns influence recognition? And how can we infer those patterns from sequence data? Here, we detail recent computational and experimental evidence associated with sequence-specific sensing. We review the mechanisms underlying the detection and discrimination of foreign sequences from self. We also describe quantitative approaches used to infer the stimulatory capacity of a given pathogen nucleic acid species, and the influence of sequence-specific sensing on host-pathogen coevolution, including endogenous sequences of foreign origin. Finally, we speculate how further studies of sequence-specific sensing will be useful to improve vaccine design, gene therapy and cancer treatment.",,"['Vabret, Nicolas', 'Bhardwaj, Nina', 'Greenbaum, Benjamin D.']",,,,
,PMC,Severe pneumonia due to infection with Candida krusei in a case of suspected Middle East respiratory syndrome: A case report and literature review,http://dx.doi.org/10.3892/etm.2016.3892,PMC5228306,,,"Candida krusei (C. krusei) pneumonia is a rare infection that is frequently associated with a poor outcome. The present study reports an unusual case of C. krusei pneumonia that was initially suspected to be a Middle East respiratory syndrome (MERS) case. A 64-year-old Saudi Arabian male patient was admitted to our hospital with complaints of cough and dyspnea that persisted for 6 days. The patient presented fever (oral temperature, 38.5°C) and slight tachypnea (25 respirations/min). A chest computerized tomography demonstrated unclear lung fields, diffuse pathological changes in the two lungs and multiple lymphadenectasis in the retrocaval and para-aortic arch area. The patient received 95–98% oxygen (6 l/min) for 24 h, as well as sulbactam sodium/cefoperazone sodium (1:1) injection (3.0 g) every 12 h, oral oseltamivir capsules (75 mg/time) twice a day, medaron injection (80 mg/time) and 750 ml fluid infusion; however, he succumbed to the disease on day 2 after admission. The infection was diagnosed by sputum smear and culture subsequent to patient mortality. A sputum smear showed a large fungal infection and sputum culture revealed the presence of C. krusei infection. Serum procalcitonin concentrations were 4.73 µg/l and 7.23 µg/l on days 2 and 3 after admission, respectively. In conclusion, the diagnosis of Candida pneumonia should be strongly considered in the presence of growth of Candida from a sputum culture and based on a suggestive computed tomography image. Tumescent diaphragmatic lymph nodes may also be an important symptom of Candida pneumonia. Treatment should be initiated immediately to improve tissue oxygenation, restore cardiovascular function and improve other organ functions.",,"['Tan, Mingming', 'Wang, Junwei', 'Hu, Peiyang', 'Wang, Bin', 'Xu, Wanghua', 'Chen, Jiao']",,,,
,PMC,Interferon gamma modulation of disease manifestation and the local antibody response to alphavirus encephalomyelitis,http://dx.doi.org/10.1099/jgv.0.000613,PMC5770845,,,"Infection of mice with Sindbis virus (SINV) produces encephalomyelitis and provides a model for examination of the central nervous system (CNS) immune response to alphavirus infection. Clearance of infectious virus is accomplished through a cooperative effort between SINV-specific antibody and IFN-γ, but the regulatory interactions are poorly understood. To determine the effects of IFN-γ on clinical disease and the antiviral immune response, C57BL/6 mice lacking IFN-γ (Ifng(−/−)) or IFN-γ receptor (Ifngr1(−/−)) were studied in comparison to WT mice. Maximum production of Ifng mRNA and IFN-γ protein in the CNS of WT and Ifngr1(−/−) mice occurred 5–7 days after infection, with higher levels of IFN-γ in Ifngr1(−/−) mice. Onset of clinical disease was earlier in mice with impaired IFN-γ signalling, although Ifngr1(−/−) mice recovered more rapidly. Ifng(−/−) and Ifngr1(−/−) mice maintained body weight better than WT mice, associated with better food intake and lower brain levels of inflammatory cytokines. Clearance of infectious virus from the spinal cords was slower, and CNS, but not serum, levels of SINV-specific IgM, IgG2a and IgG2b were lower in Ifngr1(−/−) and Ifng(−/−) mice compared to WT mice. Decreased CNS antiviral antibody was associated with lower expression of mRNAs for B-cell attracting chemokines CXCL9, CXCL10 and CXCL13 and fewer B cells in the CNS. Therefore, IFN-γ signalling increases levels of CNS pro-inflammatory cytokines, leading to clinical disease, but synergistically clears virus with SINV-specific antibody at least in part by increasing chemokine production important for infiltration of antibody-secreting B cells into the CNS.",,"['Baxter, Victoria K.', 'Griffin, Diane E.']",,,,
,PMC,Structural and functional analysis of an anchorless fibronectin-binding protein FBPS from Gram-positive bacterium Streptococcus suis,http://dx.doi.org/10.1073/pnas.1608406113,PMC5137682,,,"The anchorless fibronectin-binding proteins (FnBPs) are a group of important virulence factors for which the structures are not available and the functions are not well defined. In this study we performed comprehensive studies on a prototypic member of this group: the fibronectin-/fibrinogen-binding protein from Streptococcus suis (FBPS). The structures of the N- and C-terminal halves (FBPS-N and FBPS-C), which together cover the full-length protein in sequence, were solved at a resolution of 2.1 and 2.6 Å, respectively, and each was found to be composed of two domains with unique folds. Furthermore, we have elucidated the organization of these domains by small-angle X-ray scattering. We further showed that the fibronectin-binding site is located in FBPS-C and that FBPS promotes the adherence of S. suis to host cells by attaching the bacteria via FBPS-N. Finally, we demonstrated that FBPS functions both as an adhesin, promoting S. suis attachment to host cells, and as a bacterial factor, activating signaling pathways via β1 integrin receptors to induce chemokine production.",,"['Musyoki, Abednego Moki', 'Shi, Zhongyu', 'Xuan, Chunling', 'Lu, Guangwen', 'Qi, Jianxun', 'Gao, Feng', 'Zheng, Beiwen', 'Zhang, Qiangmin', 'Li, Yan', 'Haywood, Joel', 'Liu, Cuihua', 'Yan, Jinghua', 'Shi, Yi', 'Gao, George F.']",,,,
,PMC,Type I interferon signaling facilitates the development of IL-10-producing effector CD8(+) T cells during influenza virus infection,http://dx.doi.org/10.1002/eji.201646548,PMC5184847,,,"Recent evidence has suggested that IL-10-producing effector CD8(+) T cells play an important role in regulating excessive inflammation during acute viral infections. However, the cellular and molecular cues regulating the development of IL-10-producing effector CD8(+) T cells are not completely defined. Here we show that type I interferons (IFNs) are required for the development of IL-10-producing effector CD8(+) T cells during influenza virus infection. We find that type I IFNs can enhance IL-27 production by lung antigen presenting cells, thereby facilitating IL-10-producing CD8(+) T cell development through a CD8(+) T cell non-autonomous way. Surprisingly, we also demonstrate that direct type I IFN signaling in CD8(+) T cells is required for the maximal generation of IL-10-producing CD8(+) T cells. Type I IFN signaling in CD8(+) T cells, in cooperation with IL-27 and IL-2 signaling, promotes and sustains the expression of IRF4 and Blimp-1, two transcription factors required for the production of IL-10 by effector CD8(+) T cells. Our data have revealed a critical role of the innate antiviral effector cytokines in regulating the production of a regulatory cytokine by effector CD8(+) T cells during respiratory virus infection. The potential implications of these findings for influenza virus infection are also discussed.",,"['Jiang, Li', 'Yao, Shuyu', 'Huang, Su', 'Wright, Jeffrey', 'Braciale, Thomas J.', 'Sun, Jie']",,,,
,PMC,Amending Koch’s postulates for viral disease: when “growth in pure culture” leads to a loss of virulence,http://dx.doi.org/10.1016/j.antiviral.2016.11.002,PMC5182102,,,"It is a common laboratory practice to propagate viruses in cell culture. While convenient, these methodologies often result in unintentional genetic alterations, which have lead to adaptation and even attenuation in animal models of disease. An example is the attenuation of hantaviruses (family: Bunyaviridae, genus: Hantavirus) when cultured in vitro. In this case, viruses propagated in the natural reservoir species cause disease in nonhuman primates that closely mimics the human disease, but passaging in cell culture attenuates these viruses to the extent that do not cause any measurable disease in nonhuman primates. As efforts to develop animal models progress, it will be important to take into account the influences that culture in vitro may have on the virulence of viruses. In this review we discuss this phenomenon in the context of past and recent examples in the published literature.",,"['Prescott, Joseph', 'Feldmann, Heinz', 'Safronetz, David']",,,,
,PMC,"How social structures, space, and behaviors shape the spread of infectious diseases using chikungunya as a case study",http://dx.doi.org/10.1073/pnas.1611391113,PMC5127331,,,"Whether an individual becomes infected in an infectious disease outbreak depends on many interconnected risk factors, which may relate to characteristics of the individual (e.g., age, sex), his or her close relatives (e.g., household members), or the wider community. Studies monitoring individuals in households or schools have helped elucidate the determinants of transmission in small social structures due to advances in statistical modeling; but such an approach has so far largely failed to consider individuals in the wider context they live in. Here, we used an outbreak of chikungunya in a rural community in Bangladesh as a case study to obtain a more comprehensive characterization of risk factors in disease spread. We developed Bayesian data augmentation approaches to account for uncertainty in the source of infection, recall uncertainty, and unobserved infection dates. We found that the probability of chikungunya transmission was 12% [95% credible interval (CI): 8–17%] between household members but dropped to 0.3% for those living 50 m away (95% CI: 0.2–0.5%). Overall, the mean transmission distance was 95 m (95% CI: 77–113 m). Females were 1.5 times more likely to become infected than males (95% CI: 1.2–1.8), which was virtually identical to the relative risk of being at home estimated from an independent human movement study in the country. Reported daily use of antimosquito coils had no detectable impact on transmission. This study shows how the complex interplay between the characteristics of an individual and his or her close and wider environment contributes to the shaping of infectious disease epidemics.",,"['Salje, Henrik', 'Lessler, Justin', 'Paul, Kishor Kumar', 'Azman, Andrew S.', 'Rahman, M. Waliur', 'Rahman, Mahmudur', 'Cummings, Derek', 'Gurley, Emily S.', 'Cauchemez, Simon']",,,,
,PMC,Keeping it in check: chronic viral infection and antiviral immunity in the brain,http://dx.doi.org/10.1038/nrn.2016.140,PMC5477650,,,"It is becoming clear that the manner by which the immune response resolves or contains infection by a pathogen varies according to the tissue that is affected. Unlike many peripheral cell types, CNS neurons are generally non-renewable. Thus, the cytolytic and inflammatory strategies that are effective in controlling infections in the periphery could be damaging if deployed in the CNS. Perhaps for this reason, the immune response to some CNS viral infections favours maintenance of neuronal integrity and non-neurolytic viral control. This modified immune response — when combined with the unique anatomy and physiology of the CNS — provides an ideal environment for the maintenance of viral genomes, including those of RNA viruses. Therefore, it is possible that such viruses can reactivate long after initial viral exposure, contributing to CNS disease.",,"['Miller, Katelyn D.', 'Schnell, Matthias J.', 'Rall, Glenn F.']",,,,
,PMC,Ebola virus glycoprotein with increased infectivity dominated the 2013–2016 epidemic,http://dx.doi.org/10.1016/j.cell.2016.10.014,PMC5115602,,,"The magnitude of the 2013–2016 Ebola virus disease (EVD) epidemic enabled an unprecedented number of viral mutations to occur over successive human-to-human transmission events, increasing the probability that adaptation to the human host occurred during the outbreak. We investigated one nonsynonymous mutation, Ebola virus (EBOV) glycoprotein (GP) mutant A82V, for its effect on viral infectivity. This mutation, located at the NPC1-binding site on EBOV GP, occurred early in the 2013–2016 outbreak and rose to high frequency. We found that GP-A82V had heightened ability to infect primate cells, including human dendritic cells. The increased infectivity was restricted to cells that have primate-specific NPC1 sequences at the EBOV interface, suggesting that this mutation was indeed an adaptation to the human host. GP-A82V was associated with increased mortality, consistent with the hypothesis that the heightened intrinsic infectivity of GP-A82V contributed to disease severity during the EVD epidemic.",,"['Diehl, William E.', 'Lin, Aaron E.', 'Grubaugh, Nathan D.', 'Carvalho, Luiz Max', 'Kim, Kyusik', 'Kyawe, Pyae Phyo', 'McCauley, Sean M.', 'Donnard, Elisa', 'Kucukural, Alper', 'McDonel, Patrick', 'Schaffner, Stephen F.', 'Garber, Manuel', 'Rambaut, Andrew', 'Andersen, Kristian G.', 'Sabeti, Pardis C.', 'Luban, Jeremy']",,,,
,PMC,In the national epidemiological bulletins – a selection from current issues,http://dx.doi.org/10.2807/1560-7917.ES.2016.21.44.30387,PMC5114482,,CC BY,,2016 Nov 3,,Euro Surveill,,,
,PMC,High-fat diet-induced glucose dysregulation is independent of changes in islet ACE2 in mice,http://dx.doi.org/10.1152/ajpregu.00362.2016,PMC5256982,,,"While restoration of ACE2 activity in the pancreas leads to improvement of glycemia in experimental models of Type 2 diabetes, global deficiency in ACE2 disrupts β-cell function and impairs glucose tolerance in mice, demonstrating the physiological role of ACE2 in glucose homeostasis. Although the contribution of pancreatic ACE2 to glucose regulation has been demonstrated in genetic models of diabetes and in models with overexpression of the renin-angiotensin system (RAS), it is unclear whether islet ACE2 is involved in glycemic control in common models of human Type 2 diabetes. To determine whether diet-induced diabetes deregulates glucose homeostasis via reduction of ACE2 in the pancreatic islets, wild-type (WT) and ACE2 knockout (KO) male mice were fed a high-fat diet (HFD) for 16 wk. ACE2 KO mice were more susceptible than WT mice to HFD-mediated glycemic dysregulation. Islet ACE2 activity and expression of various genes, including ANG II type 1a receptor (mAT(1a)R) were then assessed. Surprisingly, we observed no change in islet ACE2 activity and expression despite local RAS overactivity, indicated by an upregulation of mAT(1a)R expression. Despite a predominant expression in islet α-cells, further investigation highlighted a minor role for ACE2 on glucagon expression. Further, pancreatic ACE2 gene therapy improved glycemia in HFD-fed WT mice, leading to enhanced glucose-stimulated insulin secretion, reduced pancreatic ANG II levels, fibrosis, and ADAM17 activity. Altogether, our study demonstrates that HFD feeding increases RAS activity and mediates glycemic dysregulation likely through loss of ACE2 present outside the islets but independently of changes in islet ACE2.",,"['Chodavarapu, Harshita', 'Chhabra, Kavaljit H.', 'Xia, Huijing', 'Shenoy, Vinayak', 'Yue, Xinping', 'Lazartigues, Eric']",,,,
,PMC,West Nile Virus Infection in Human and Mouse Cornea Tissue,http://dx.doi.org/10.4269/ajtmh.16-0256,PMC5094237,,,"The purpose of this study was to determine the in vitro and ex vivo susceptibility of human corneal cells to West Nile virus (WNV) infection and evaluate the ability of the virus to disseminate to the corneas of infected mice. Human corneal epithelial cells were challenged with WNV, incubated for 1–6 days, and tested for evidence of WNV infection. Viral RNA and antigen were detected at every time point, and the virus reached a peak titer of 2.5 × 10(7) plaque-forming units (pfu)/mL at 3 days postinoculation (PI). Corneas procured from donors were incubated in culture dishes containing WNV for 1–5 days and tested for evidence of WNV. Viral RNA and antigen were detected, and the virus reached a mean peak titer of 4.9 × 10(4) pfu/mL at 5 days PI. Mice were inoculated intraperitoneally with WNV, and their eyes were harvested at 2, 5, and 8 days PI and tested for evidence of WNV. Viral RNA was detected in corneas of four of nine systemically infected mice as early as 2 days PI. We conclude that human corneal cells support WNV replication in vitro and ex vivo, and WNV may disseminate into the corneas of experimentally infected mice. These findings indicate that corneal transmission cannot be ruled out as a novel mode of human-to-human WNV transmission and additional experiments should be conducted to assess this risk further.",,"['Blitvich, Bradley J.', 'Wang, Tian', 'Saxena, Vandana', 'Zeng, Shemin', 'Harmon, Karen M.', 'Raymond, Matthew D.', 'Goins, Kenneth M.', 'Reed, Cynthia R.', 'Mullins, Robert F.', 'Greiner, Mark A.']",,,,
,PMC,The macro domain as fusion tag for carrier‐driven crystallization,http://dx.doi.org/10.1002/pro.3073,PMC5275734,,,"Obtaining well‐ordered crystals remains a significant challenge in protein X‐ray crystallography. Carrier‐driven crystallization can facilitate crystal formation and structure solution of difficult target proteins. We obtained crystals of the small and highly flexible SPX domain from the yeast vacuolar transporter chaperone 4 (Vtc4) when fused to a C‐terminal, non‐cleavable macro tag derived from human histone macroH2A1.1. Initial crystals diffracted to 3.3 Å resolution. Reductive protein methylation of the fusion protein yielded a new crystal form diffracting to 2.1 Å. The structures were solved by molecular replacement, using isolated macro domain structures as search models. Our findings suggest that macro domain tags can be employed in recombinant protein expression in E. coli, and in carrier‐driven crystallization.",,"['Wild, Rebekka', 'Hothorn, Michael']",,,,
,PMC,Differences in innate immune response gene regulation in the middle ear of children who are otitis prone and in those not otitis prone,http://dx.doi.org/10.2500/ajra.2016.30.4393,PMC5108842,,,"OBJECTIVE: Acute otitis media (AOM) causes an inflammatory response in the middle ear. We assessed differences in innate immune responses involved in bacterial defense at onset of AOM in children who were stringently defined as otitis prone (sOP) and children not otitis prone (NOP). STUDY DESIGN: Innate immune genes analysis from middle ear fluid (MEF) samples of children. METHODS: Genes of toll-like receptors (TLR), nod-like and retinoic acid-inducible gene-I-like receptors, downstream effectors important for inflammation and apoptosis, including cytokines and chemokines, were studied from MEF samples by using a real-time polymerase chain reaction array. Protein levels of differentially regulated genes were measured by Luminex. RESULTS: Gene expression in MEF among children who were sOP was significantly different in upregulation of interleukin 8, secretory leukocyte peptidase inhibitor, and chemokine (C-C motif) ligand 3, and in downregulation of interferon regulatory factor 7 and its related signaling molecules interferon alpha, Toll-like receptor adaptor molecule 2, chemokine (C-C motif) ligand 5, and mitogen-activated protein kinase 8 compared with children who were NOP. Differences in innate gene regulation were similar when AOM was caused by Streptococcus pneumoniae or nontypeable Haemophilus influenzae. CONCLUSION: Innate-immune response genes are differentially regulated in children who were sOP compared with children with NOP.",,"['Kaur, Ravinder', 'Casey, Janet', 'Pichichero, Michael']",,,,
,PMC,"Treating the host response to emerging virus diseases: lessons learned from sepsis, pneumonia, influenza and Ebola",http://dx.doi.org/10.21037/atm.2016.11.03,PMC5124618,,,"There is an ongoing threat of epidemic or pandemic diseases that could be caused by influenza, Ebola or other emerging viruses. It will be difficult and costly to develop new drugs that target each of these viruses. Statins and angiotensin receptor blockers (ARBs) have been effective in treating patients with sepsis, pneumonia and influenza, and a statin/ARB combination appeared to dramatically reduce mortality during the recent Ebola outbreak. These drugs target (among other things) the endothelial dysfunction found in all of these diseases. Most scientists work on new drugs that target viruses, and few accept the idea of treating the host response with generic drugs. A great deal of research will be needed to show conclusively that these drugs work, and this will require the support of public agencies and foundations. Investigators in developing countries should take an active role in this research. If the next Public Health Emergency of International Concern is caused by an emerging virus, a “top down” approach to developing specific new drug treatments is unlikely to be effective. However, a “bottom up” approach to treatment that targets the host response to these viruses by using widely available and inexpensive generic drugs could reduce mortality in any country with a basic health care system. In doing so, it would make an immeasurable contribution to global equity and global security.",,"Fedson, David S.",,,,
,PMC,Alternative Watson–Crick Synthetic Genetic Systems,http://dx.doi.org/10.1101/cshperspect.a023770,PMC5088529,,,"In its “grand challenge” format in chemistry, “synthesis” as an activity sets out a goal that is substantially beyond current theoretical and technological capabilities. In pursuit of this goal, scientists are forced across uncharted territory, where they must answer unscripted questions and solve unscripted problems, creating new theories and new technologies in ways that would not be created by hypothesis-directed research. Thus, synthesis drives discovery and paradigm changes in ways that analysis cannot. Described here are the products that have arisen so far through the pursuit of one grand challenge in synthetic biology: Recreate the genetics, catalysis, evolution, and adaptation that we value in life, but using genetic and catalytic biopolymers different from those that have been delivered to us by natural history on Earth. The outcomes in technology include new diagnostic tools that have helped personalize the care of hundreds of thousands of patients worldwide. In science, the effort has generated a fundamentally different view of DNA, RNA, and how they work.",,"['Benner, Steven A.', 'Karalkar, Nilesh B.', 'Hoshika, Shuichi', 'Laos, Roberto', 'Shaw, Ryan W.', 'Matsuura, Mariko', 'Fajardo, Diego', 'Moussatche, Patricia']",,,,
,PMC,Kawasaki disease for dermatologists,http://dx.doi.org/10.4103/2229-5178.193903,PMC5134159,27990380,CC BY-NC-SA,"Kawasaki disease (KD) is a systemic vasculitis that mostly affects children below the age of 5. The vasculitis involves arteries of medium size, especially the coronaries. Various etiologies have been proposed including association with micro-organisms, bacterial superantigens, and genetic factors, however, the exact cause remains unknown. There is no specific laboratory test for KD. Diagnosis is clinical and depends upon the presence of fever for ≥5 days and 4 or more of five principal features, viz. polymorphous exanthem, extremity changes, mucosal changes involving the lips and oral cavity, bilateral bulbar conjunctival injection, and unilateral cervical lymphadenopathy. The term “incomplete KD” refers to the presence of fever and less than four principal clinical features. Recognition of this group of patients is important because it is usually seen in infants and risk of coronary abnormalities is increased probably because of delays in diagnosis. However, what appears to be “incomplete” at a given point of time may not actually be so because some of the features may have already subsided and others may evolve over time. Hence, a detailed dermatological examination is warranted in all cases, especially in incomplete KD, to ensure timely diagnosis. Although KD is a self-limiting disease in most patients, coronary artery abnormalities (CAAs) including coronary dilatations and aneurysms may develop in up to 25% of untreated patients. CAAs are the most common cause of morbidity and mortality in patients with KD. Treatment is aimed at reducing inflammation and consists of intravenous immunoglobulin (IVIG) along with aspirin. Despite treatment, some patients may still develop CAAs, and hence, long-term follow up is of utmost importance.",2016 Nov-Dec,"['Gupta, Aman', 'Singh, Surjit']",Indian Dermatol Online J,,,
,PMC,Borna Disease Virus Assembles Porous Cage-like Viral Factories in the Nucleus,http://dx.doi.org/10.1074/jbc.M116.746396,PMC5207054,,,"Animal-derived RNA viruses frequently generate viral factories in infected cells. However, the details of how RNA viruses build such intracellular structures are poorly understood. In this study, we examined the structure and formation of the viral factories, called viral speckle of transcripts (vSPOTs), that are produced in the nuclei of host cells by Borna disease virus (BDV). Super-resolution microscopic analysis showed that BDV assembled vSPOTs as intranuclear cage-like structures with 59–180-nm pores. The viral nucleoprotein formed the exoskeletons of vSPOTs, whereas the other viral proteins appeared to be mainly localized within these structures. In addition, stochastic optical reconstruction microscopy revealed that filamentous structures resembling viral ribonucleoprotein complexes (RNPs) appeared to protrude from the outer surfaces of the vSPOTs. We also found that vSPOTs disintegrated into RNPs concurrently with the breakdown of the nuclear envelope during mitosis. These observations demonstrated that BDV generates viral replication factories whose shape and formation are regulated, suggesting the mechanism of the integrity of RNA virus persistent infection in the nucleus.",,"['Hirai, Yuya', 'Hirano, Yasuhiro', 'Matsuda, Atsushi', 'Hiraoka, Yasushi', 'Honda, Tomoyuki', 'Tomonaga, Keizo']",,,,
,PMC,Pharmacological Management and Prevention Of Exacerbations of Chronic Obstructive Pulmonary Disease in Hospitalized Patients,,PMC5083078,,,"Rapid-acting bronchodilators, systemic corticosteroids, and antibiotics are among the keys to managing exacerbations of chronic obstructive pulmonary disease. Preventing exacerbations should also be a component of therapy for the disease.",,"['Dixit, Deepali', 'Bridgeman, Mary Barna', 'Madduri, Rani Patel', 'Kumar, Samir T.', 'Cawley, Michael J.']",,,,
,PMC,Medicine and diplomacy,http://dx.doi.org/10.11622/smedj.2016176,PMC5331141,,,,,"Koh, Tommy",,,,
,PMC,GRAFT LOSS AND CLAD ONSET IS HASTENED BY VIRAL PNEUMONIA AFTER LUNG TRANSPLANTATION,http://dx.doi.org/10.1097/TP.0000000000001346,PMC5077663,,,"BACKGROUND: Community acquired respiratory virus (CARV) infections occur frequently after lung transplantation and may adversely impact outcomes. We hypothesized that while asymptomatic carriage would not increase the risk of chronic lung allograft dysfunction (CLAD) and graft loss, severe infection would. METHODS: All lung transplant cases between January 2000 and July 2013 performed at our center were reviewed for respiratory viral samples. Each isolation of virus was classified according to clinical level of severity: asymptomatic, symptomatic without pneumonia, and viral pneumonia. Multivariate Cox modeling was employed to assess the impact of CARV isolation on progression to CLAD and graft loss. RESULTS: 4408 specimens were collected from 563 total patients with 139 patients producing 324 virus positive specimens in 245 episodes of CARV infection. Overall, the risk of CLAD was elevated by viral infection (HR 1.64, p < 0.01). This risk, however, was due to viral pneumonia alone (HR 3.94, p < 0.01), without significant impact from symptomatic viral infection (HR 0.97, p = 0.94) nor from asymptomatic viral infection (HR 0.99, p = 0.98). The risk of graft loss was not increased by asymptomatic CARV infection (HR 0.74, p = 0.37) nor symptomatic CARV infection (HR 1.39, p = 0.41). Viral pneumonia did, however, significantly increase the risk of graft loss (HR 2.78, p < 0.01). CONCLUSIONS: With respect to CARV, only viral pneumonia increased the risk of both CLAD and graft loss after lung transplantation. In the absence of pneumonia, respiratory viruses had no impact on measured outcomes.",,"['Allyn, Paul R.', 'Duffy, Erin L.', 'Humphries, Romney M.', 'Injean, Patil', 'Weigt, S. Samuel', 'Saggar, Rajan', 'Shino, Michael Y.', 'Lynch, Joseph P.', 'Ardehali, Abbas', 'Kubak, Bernard', 'Tseng, Chi-Hong', 'Belperio, John A.', 'Ross, David J.', 'Gregson, Aric L.']",,,,
,PMC,SARS-CoV 3CL protease cleaves its C-terminal autoprocessing site by novel subsite cooperativity,http://dx.doi.org/10.1073/pnas.1601327113,PMC5135343,,,"The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome coronavirus (SARS-CoV) cleaves 11 sites in the polyproteins, including its own N- and C-terminal autoprocessing sites, by recognizing P4–P1 and P1′. In this study, we determined the crystal structure of 3CL(pro) with the C-terminal prosequence and the catalytic-site C145A mutation, in which the enzyme binds the C-terminal prosequence of another molecule. Surprisingly, Phe at the P3′ position [Phe(P3′)] is snugly accommodated in the S3′ pocket. Mutations of Phe(P3′) impaired the C-terminal autoprocessing, but did not affect N-terminal autoprocessing. This difference was ascribed to the P2 residue, Phe(P2) and Leu(P2), in the C- and N-terminal sites, as follows. The S3′ subsite is formed by Phe(P2)-induced conformational changes of 3CL(pro) and the direct involvement of Phe(P2) itself. In contrast, the N-terminal prosequence with Leu(P2) does not cause such conformational changes for the S3′ subsite formation. In fact, the mutation of Phe(P2) to Leu in the C-terminal autoprocessing site abolishes the dependence on Phe(P3′). These mechanisms explain why Phe is required at the P3' position when the P2 position is occupied by Phe rather than Leu, which reveals a type of subsite cooperativity. Moreover, the peptide consisting of P4–P1 with Leu(P2) inhibits protease activity, whereas that with Phe(P2) exhibits a much smaller inhibitory effect, because Phe(P3′) is missing. Thus, this subsite cooperativity likely exists to avoid the autoinhibition of the enzyme by its mature C-terminal sequence, and to retain the efficient C-terminal autoprocessing by the use of Phe(P2).",,"['Muramatsu, Tomonari', 'Takemoto, Chie', 'Kim, Yong-Tae', 'Wang, Hongfei', 'Nishii, Wataru', 'Terada, Takaho', 'Shirouzu, Mikako', 'Yokoyama, Shigeyuki']",,,,
,PMC,Vaccination strategies against respiratory syncytial virus,http://dx.doi.org/10.1073/pnas.1522597113,PMC5135296,,,"Respiratory syncytial virus (RSV) is the most common cause of US infant hospitalization. Additionally, RSV is responsible for 10,000 deaths annually among the elderly across the United States, and accounts for nearly as many hospitalizations as influenza. Currently, several RSV vaccine candidates are under development to target different age groups. To evaluate the potential effectiveness of age-specific vaccination strategies in averting RSV incidence, we developed a transmission model that integrates data on daily infectious viral load and changes of behavior associated with RSV symptoms. Calibrating to RSV weekly incidence rates in Texas, California, Colorado, and Pennsylvania, we show that in all states considered, an infected child under 5 y of age is more than twice as likely as a person over 50 y of age to transmit the virus. Geographic variability in the effectiveness of a vaccination program across states arises from interplay between seasonality patterns, population demography, vaccination uptake, and vaccine mechanism of action. Regardless of these variabilities, our analysis showed that allocating vaccine to children under 5 y of age would be the most efficient strategy per dose to avert RSV in both children and adults. Furthermore, due to substantial indirect protection, the targeting of children is even predicted to reduce RSV in the elderly more than directly vaccinating the elderly themselves. Our results can help inform ongoing clinical trials and future recommendations on RSV vaccination.",,"['Yamin, Dan', 'Jones, Forrest K.', 'DeVincenzo, John P.', 'Gertler, Shai', 'Kobiler, Oren', 'Townsend, Jeffrey P.', 'Galvani, Alison P.']",,,,
,PMC,Anti‐ageing active ingredients from herbs and nutraceuticals used in traditional Chinese medicine: pharmacological mechanisms and implications for drug discovery,http://dx.doi.org/10.1111/bph.13631,PMC5429334,,,"Ageing, an unanswered question in the medical field, is a multifactorial process that results in a progressive functional decline in cells, tissues and organisms. Although it is impossible to prevent ageing, slowing down the rate of ageing is entirely possible to achieve. Traditional Chinese medicine (TCM) is characterized by the nourishing of life and its role in anti‐ageing is getting more and more attention. This article summarizes the work done on the natural products from TCM that are reported to have anti‐ageing effects, in the past two decades. The effective anti‐ageing ingredients identified can be generally divided into flavonoids, saponins, polysaccharides, alkaloids and others. Astragaloside, Cistanche tubulosa acteoside, icariin, tetrahydrocurcumin, quercetin, butein, berberine, catechin, curcumin, epigallocatechin gallate, gastrodin, 6‐Gingerol, glaucarubinone, ginsenoside Rg1, luteolin, icarisid II, naringenin, resveratrol, theaflavin, carnosic acid, catalpol, chrysophanol, cycloastragenol, emodin, galangin, echinacoside, ferulic acid, huperzine, honokiol, isoliensinine, phycocyanin, proanthocyanidins, rosmarinic acid, oxymatrine, piceid, puerarin and salvianolic acid B are specified in this review. Simultaneously, chemical structures of the monomers with anti‐ageing activities are listed, and their source, model, efficacy and mechanism are also described. The TCMs with anti‐ageing function are classified according to their action pathways, including the telomere and telomerase, the sirtuins, the mammalian target of rapamycin, AMP‐activated kinase and insulin/insulin‐like growth factor‐1 signalling pathway, free radicals scavenging and the resistance to DNA damage. Finally, Chinese compound prescription and extracts related to anti‐ageing are introduced, which provides the basis and the direction for the further development of novel and potential drugs. LINKED ARTICLES: This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc",,"['Shen, Chun‐Yan', 'Jiang, Jian‐Guo', 'Yang, Li', 'Wang, Da‐Wei', 'Zhu, Wei']",,,,
,PMC,A sequence upstream of canonical PDZ-binding motif within CFTR COOH-terminus enhances NHERF1 interaction,http://dx.doi.org/10.1152/ajplung.00363.2016,PMC5206395,,,"The development of cystic fibrosis transmembrane conductance regulator (CFTR) targeted therapy for cystic fibrosis has generated interest in maximizing membrane residence of mutant forms of CFTR by manipulating interactions with scaffold proteins, such as sodium/hydrogen exchange regulatory factor-1 (NHERF1). In this study, we explored whether COOH-terminal sequences in CFTR beyond the PDZ-binding motif influence its interaction with NHERF1. NHERF1 displayed minimal self-association in blot overlays (NHERF1, K(d) = 1,382 ± 61.1 nM) at concentrations well above physiological levels, estimated at 240 nM from RNA-sequencing and 260 nM by liquid chromatography tandem mass spectrometry in sweat gland, a key site of CFTR function in vivo. However, NHERF1 oligomerized at considerably lower concentrations (10 nM) in the presence of the last 111 amino acids of CFTR (20 nM) in blot overlays and cross-linking assays and in coimmunoprecipitations using differently tagged versions of NHERF1. Deletion and alanine mutagenesis revealed that a six-amino acid sequence (1417)EENKVR(1422) and the terminal (1478)TRL(1480) (PDZ-binding motif) in the COOH-terminus were essential for the enhanced oligomerization of NHERF1. Full-length CFTR stably expressed in Madin-Darby canine kidney epithelial cells fostered NHERF1 oligomerization that was substantially reduced (∼5-fold) on alanine substitution of EEN, KVR, or EENKVR residues or deletion of the TRL motif. Confocal fluorescent microscopy revealed that the EENKVR and TRL sequences contribute to preferential localization of CFTR to the apical membrane. Together, these results indicate that COOH-terminal sequences mediate enhanced NHERF1 interaction and facilitate the localization of CFTR, a property that could be manipulated to stabilize mutant forms of CFTR at the apical surface to maximize the effect of CFTR-targeted therapeutics.",,"['Sharma, Neeraj', 'LaRusch, Jessica', 'Sosnay, Patrick R.', 'Gottschalk, Laura B.', 'Lopez, Andrea P.', 'Pellicore, Matthew J.', 'Evans, Taylor', 'Davis, Emily', 'Atalar, Melis', 'Na, Chan-Hyun', 'Rosson, Gedge D.', 'Belchis, Deborah', 'Milewski, Michal', 'Pandey, Akhilesh', 'Cutting, Garry R.']",,,,
,PMC,"Characterization of Vesicular Stomatitis Virus Pseudotypes Bearing Essential Entry Glycoproteins gB, gD, gH, and gL of Herpes Simplex Virus 1",http://dx.doi.org/10.1128/JVI.01714-16,PMC5105666,,,"Herpes simplex viruses (HSVs) are unusual in that unlike most enveloped viruses, they require at least four entry glycoproteins, gB, gD, gH, and gL, for entry into target cells in addition to a cellular receptor for gD. The dissection of the herpes simplex virus 1 (HSV-1) entry mechanism is complicated by the presence of more than a dozen proteins on the viral envelope. To investigate HSV-1 entry requirements in a simplified system, we generated vesicular stomatitis virus (VSV) virions pseudotyped with HSV-1 essential entry glycoproteins gB, gD, gH, and gL but lacking the native VSV fusogen G. These virions, referred to here as VSVΔG-BHLD virions, infected a cell line expressing a gD receptor, demonstrating for the first time that the four essential entry glycoproteins of HSV-1 are not only required but also sufficient for cell entry. To our knowledge, this is the first time the VSV pseudotyping system has been successfully extended beyond two proteins. Entry of pseudotyped virions required a gD receptor and was inhibited by HSV-1 specific anti-gB or anti-gH/gL neutralizing antibodies, which suggests that membrane fusion during the entry of the pseudotyped virions shares common requirements with the membrane fusion involved in HSV-1 entry and HSV-1-mediated syncytium formation. The HSV pseudotyping system established in this study presents a novel tool for systematic exploration of the HSV entry and membrane fusion mechanisms. IMPORTANCE Herpes simplex viruses (HSVs) are human pathogens that can cause cold sores, genital herpes, and blindness. No vaccines or preventatives are available. HSV entry into cells—a prerequisite for a successful infection—is a complex process that involves multiple viral and host proteins and occurs by different routes. Detailed mechanistic knowledge of the HSV entry is important for understanding its pathogenesis and would benefit antiviral and vaccine development, yet the presence of more than a dozen proteins on the viral envelope complicates the dissection of the HSV entry mechanisms. In this study, we generated heterologous virions displaying the four essential entry proteins of HSV-1 and showed that they are capable of cell entry and, like HSV-1, require all four entry glycoproteins along with a gD receptor. This HSV pseudotyping system pioneered in this work opens doors for future systematic exploration of the herpesvirus entry mechanisms.",,"['Rogalin, Henry B.', 'Heldwein, Ekaterina E.']",,,,
,PMC,Assessment of the Clinical Performance of Platelet Concentrates Treated by Pathogen Reduction Technology in Santiago de Compostela,http://dx.doi.org/10.1159/000447643,PMC5318921,,,"INTRODUCTION: This study assessed the feasibility, performance, and safety of Mirasol®-treated platelet concentrates (M-PC) stored for up to 7 days. METHODS: This prospective observational study was approved by the ethical committee of the University Clinic of Santiago de Compostela. Informed consent was asked from patients receiving M-PC. M-PCs were treated with the Mirasol system according to the manufacturer's instructions. Thrombocytopenic patients were transfused according to the Spanish transfusion guidelines. Post-transfusion platelet counts were measured at 1 h and/or 24 h after transfusion. Post-transfusion surveillance of patients was maintained during the study. RESULTS: Data from 54 evaluable patients and 135 transfusions were analyzed. The mean age of patients was 58 years. The mean age of M-PC at transfusion was 3.6 days. The mean platelet dose was 3.7 × 10(11). The transfusion responses measured as mean corrected count increment 1 h after transfusion (CCI(1h)) and CCI(24h) were 9,659 and 4,751, respectively. 65% of transfusions resulted in CCI(1h) values ≥ 7,500. 51% of transfusions resulted in CCI(24h) values ≥ 4,500. CONCLUSION: The use of M-PC in the supportive treatment proved to be safe and effective for this cohort of thrombocytopenic patients.",,"['Vilariño, M. Dolores', 'Castrillo, Azucena', 'Campos, Alfredo', 'Kilian, Rachel', 'Villamayor, Mercedes', 'Cardoso, Marcia']",,,,
,PMC,Eradicating infectious disease using weakly transmissible vaccines,http://dx.doi.org/10.1098/rspb.2016.1903,PMC5095390,,,"Viral vaccines have had remarkable positive impacts on human health as well as the health of domestic animal populations. Despite impressive vaccine successes, however, many infectious diseases cannot yet be efficiently controlled or eradicated through vaccination, often because it is impossible to vaccinate a sufficient proportion of the population. Recent advances in molecular biology suggest that the centuries-old method of individual-based vaccine delivery may be on the cusp of a major revolution. Specifically, genetic engineering brings to life the possibility of a live, transmissible vaccine. Unfortunately, releasing a highly transmissible vaccine poses substantial evolutionary risks, including reversion to high virulence as has been documented for the oral polio vaccine. An alternative, and far safer approach, is to rely on genetically engineered and weakly transmissible vaccines that have reduced scope for evolutionary reversion. Here, we use mathematical models to evaluate the potential efficacy of such weakly transmissible vaccines. Our results demonstrate that vaccines with even a modest ability to transmit can significantly lower the incidence of infectious disease and facilitate eradication efforts. Consequently, weakly transmissible vaccines could provide an important tool for controlling infectious disease in wild and domestic animal populations and for reducing the risks of emerging infectious disease in humans.",,"['Nuismer, Scott L.', 'Althouse, Benjamin M.', 'May, Ryan', 'Bull, James J.', 'Stromberg, Sean P.', 'Antia, Rustom']",,,,
,PMC,Glycan-Protein Interactions in Viral Pathogenesis,http://dx.doi.org/10.1016/j.sbi.2016.10.003,PMC5526076,,,"The surfaces of host cells and viruses are decorated by complex glycans, which play multifaceted roles in the dynamic interplay between the virus and the host including viral entry into host cell, modulation of proteolytic cleavage of viral proteins, recognition and neutralization of virus by host immune system. These roles are mediated by specific multivalent interactions of glycans with their cognate proteins (generally termed as glycan-binding proteins or GBPs or lectins). The advances in tools and technologies to chemically synthesize and structurally characterize glycans and glycan-GBP interactions have offered several insights into the role of glycan-GBP interactions in viral pathogenesis and have presented opportunities to target these interactions for novel antiviral therapeutic or vaccine strategies. This review covers aspects of role of host cell surface glycan receptors and viral surface glycans in viral pathogenesis and offers perspectives on how to employ various analytical tools to target glycan-GBP interactions.",,"['Raman, Rahul', 'Tharakaraman, Kannan', 'Sasisekharan, V', 'Sasisekharan, Ram']",,,,
,PMC,Management of severe traumatic brain injury and acute respiratory distress syndrome using pumped extracorporeal carbon dioxide removal device,http://dx.doi.org/10.1177/1751143716676821,PMC5606366,,,"The effects of a high carbon dioxide on cerebral perfusion and intracranial pressure are well known. We report the case of a man who presented after with a severe traumatic brain injury including intracranial and extradural haemorrhage. Neuroprotective ventilation was impossible without supramaximal tidal volumes due to a combination of chest trauma and severe bronchospasm. A pump driven Novalung iLA active® system was inserted to achieve both ARDSnet ventilation and a lowering of intracranial pressure. To our knowledge, this is the first time this system has been used to this effect. The patient went on to make a good recovery.",,"['Martindale, Tim', 'McGlone, Phillip', 'Chambers, Robert', 'Fennell, Jon']",,,,
,PMC,Prostaglandin E2 promotes intestinal repair through an adaptive cellular response of the epithelium,http://dx.doi.org/10.15252/embj.201694660,PMC5210160,,,"Adaptive cellular responses are often required during wound repair. Following disruption of the intestinal epithelium, wound‐associated epithelial (WAE) cells form the initial barrier over the wound. Our goal was to determine the critical factor that promotes WAE cell differentiation. Using an adaptation of our in vitro primary epithelial cell culture system, we found that prostaglandin E2 (PGE (2)) signaling through one of its receptors, Ptger4, was sufficient to drive a differentiation state morphologically and transcriptionally similar to in vivo WAE cells. WAE cell differentiation was a permanent state and dominant over enterocyte differentiation in plasticity experiments. WAE cell differentiation was triggered by nuclear β‐catenin signaling independent of canonical Wnt signaling. Creation of WAE cells via the PGE (2)‐Ptger4 pathway was required in vivo, as mice with loss of Ptger4 in the intestinal epithelium did not produce WAE cells and exhibited impaired wound repair. Our results demonstrate a mechanism by which WAE cells are formed by PGE (2) and suggest a process of adaptive cellular reprogramming of the intestinal epithelium that occurs to ensure proper repair to injury.",,"['Miyoshi, Hiroyuki', 'VanDussen, Kelli L', 'Malvin, Nicole P', 'Ryu, Stacy H', 'Wang, Yi', 'Sonnek, Naomi M', 'Lai, Chin‐Wen', 'Stappenbeck, Thaddeus S']",,,,
,PMC,Comparison of BacT/Alert FAN and FAN Plus Bottles with Conventional Medium for Culturing Cerebrospinal Fluid,http://dx.doi.org/10.1128/JCM.01147-16,PMC5078565,,,"We compared the BacT/Alert system FAN and FAN Plus media to conventional media for culturing cerebrospinal fluid (CSF) with 2,545 samples. FAN/FAN Plus bottles showed better performance for isolating microorganisms in CSF than conventional media (positive rate, 7.2% [182/2,545] versus 3.1% [80/2,545]). The incremental recovery rate of Cryptococcus neoformans from FAN Plus bottles was higher than that from FAN bottles.",,"['Yoo, In Young', 'Chun, Sejong', 'Song, Dong Joon', 'Huh, Hee Jae', 'Lee, Nam Yong']",,,,
,PMC,Accurate Detection of Avian Respiratory Viruses by Use of Multiplex PCR-Based Luminex Suspension Microarray Assay,http://dx.doi.org/10.1128/JCM.00610-16,PMC5078549,,,"A novel oligonucleotide suspension microarray (Luminex microsphere system) was developed for the rapid detection of avian respiratory viruses of major clinical importance. This test was optimized and validated with 70 clinical samples. The developed tool was accurate for high-throughput detection and differentiation of the most important avian respiratory viruses: avian influenza virus (AIV), Newcastle disease virus (NDV), infection bronchitis virus (IBV), and infectious laryngotracheitis virus (ILTV) in single- and mixed-virus infections. A multiplex reverse transcriptase PCR (RT-PCR), followed by a monoplex or a multiplex Luminex assays, were realized using a Luminex 200 analyzer instrument. The sensitivity, specificity, and reproducibility of the multiplex DNA suspension microarray system were evaluated. The results showed no significant differences in the median fluorescence intensity (MFI) value in monoplex and multiplex Luminex assays. The sensitivity and specificity proved to be completely concordant with monoplex real-time RT-PCR. We demonstrated that the multiplex DNA suspension microarray system is an accurate, high-throughput, and relatively simple method for the rapid detection of the main respiratory viruses of poultry.",,"['Laamiri, Nacira', 'Fällgren, Pia', 'Zohari, Siamak', 'Ben Ali, Jaouher', 'Ghram, Abdeljelil', 'Leijon, Mikael', 'Hmila, Issam']",,,,
,PMC,Laboratory Diagnosis of Infections in Cancer Patients: Challenges and Opportunities,http://dx.doi.org/10.1128/JCM.00604-16,PMC5078537,,,"Infections remain a significant cause of morbidity and mortality in cancer patients. The differential diagnosis for these patients is often wide, and the timely selection of the right clinical tests can have a significant impact on their survival. However, laboratory findings with current methodologies are often negative, challenging clinicians and laboratorians to continue the search for the responsible pathogen. Novel methodologies are providing increased sensitivity and rapid turnaround time to results but also challenging our interpretation of what is a clinically significant pathogen in cancer patients. This minireview provides an overview of the most common infections in cancer patients and discusses some of the challenges and opportunities for the clinical microbiologist supporting the care of cancer patients.",,"Babady, N. Esther",,,,
,PMC,Screening and analysis of breast cancer genes regulated by the human mammary microenvironment in a humanized mouse model,http://dx.doi.org/10.3892/ol.2016.5310,PMC5228194,,,"Tumor microenvironments play critical regulatory roles in tumor growth. Although mouse cancer models have contributed to the understanding of human tumor biology, the effectiveness of mouse cancer models is limited by the inability of the models to accurately present humanized tumor microenvironments. Previously, a humanized breast cancer model in severe combined immunodeficiency mice was established, in which human breast cancer tissue was implanted subcutaneously, followed by injection of human breast cancer cells. It was demonstrated that breast cancer cells showed improved growth in the human mammary microenvironment compared with a conventional subcutaneous mouse model. In the present study, the novel mouse model and microarray technology was used to analyze changes in the expression of genes in breast cancer cells that are regulated by the human mammary microenvironment. Humanized breast and conventional subcutaneous mouse models were established, and orthotopic tumor cells were obtained from orthotopic tumor masses by primary culture. An expression microarray using Illumina HumanHT-12 v4 Expression BeadChip and database analyses were performed to investigate changes in gene expression between tumors from each microenvironment. A total of 94 genes were differentially expressed between the primary cells cultured from the humanized and conventional mouse models. Significant upregulation of genes that promote cell proliferation and metastasis or inhibit apoptosis, such as SH3-domain binding protein 5 (BTK-associated), sodium/chloride cotransporter 3 and periostin, osteoblast specific factor, and genes that promote angiogenesis, such as KIAA1618, was also noted. Other genes that restrain cell proliferation and accelerate cell apoptosis, including tripartite motif containing TRIM36 and NES1, were downregulated. The present results revealed differences in various aspects of tumor growth and metabolism between the two model groups and indicated the functional changes specific to the human mammary microenvironment.",,"['Zheng, Mingjie', 'Wang, Jue', 'Ling, Lijun', 'Xue, Dandan', 'Wang, Shui', 'Zhao, Yi']",,,,
,PMC,Synthetically derived bat influenza A-like viruses reveal a cell type- but not species-specific tropism,http://dx.doi.org/10.1073/pnas.1608821113,PMC5111703,,,"Two novel influenza A-like viral genome sequences have recently been identified in Central and South American fruit bats and provisionally designated “HL17NL10” and “HL18NL11.” All efforts to isolate infectious virus from bats or to generate these viruses by reverse genetics have failed to date. Recombinant vesicular stomatitis virus (VSV) encoding the hemagglutinin-like envelope glycoproteins HL17 or HL18 in place of the VSV glycoprotein were generated to identify cell lines that are susceptible to bat influenza A-like virus entry. More than 30 cell lines derived from various species were screened but only a few cell lines were found to be susceptible, including Madin–Darby canine kidney type II (MDCK II) cells. The identification of cell lines susceptible to VSV chimeras allowed us to recover recombinant HL17NL10 and HL18NL11 viruses from synthetic DNA. Both influenza A-like viruses established a productive infection in MDCK II cells; however, HL18NL11 replicated more efficiently than HL17NL10 in this cell line. Unlike conventional influenza A viruses, bat influenza A-like viruses started the infection preferentially at the basolateral membrane of polarized MDCK II cells; however, similar to conventional influenza A viruses, bat influenza A-like viruses were released primarily from the apical site. The ability of HL18NL11 or HL17NL10 viruses to infect canine and human cells might reflect a zoonotic potential of these recently identified bat viruses.",,"['Moreira, Étori Aguiar', 'Locher, Samira', 'Kolesnikova, Larissa', 'Bolte, Hardin', 'Aydillo, Teresa', 'García-Sastre, Adolfo', 'Schwemmle, Martin', 'Zimmer, Gert']",,,,
,PMC,Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein-Based Cell-Cell Fusion Assay,http://dx.doi.org/10.1128/AAC.01043-16,PMC5075056,,,"Middle East respiratory syndrome (MERS) is an emerging infectious disease associated with a relatively high mortality rate of approximately 40%. MERS is caused by MERS coronavirus (MERS-CoV) infection, and no specific drugs or vaccines are currently available to prevent MERS-CoV infection. MERS-CoV is an enveloped virus, and its envelope protein (S protein) mediates membrane fusion at the plasma membrane or endosomal membrane. Multiple proteolysis by host proteases, such as furin, transmembrane protease serine 2 (TMPRSS2), and cathepsins, causes the S protein to become fusion competent. TMPRSS2, which is localized to the plasma membrane, is a serine protease responsible for the proteolysis of S in the post-receptor-binding stage. Here, we developed a cell-based fusion assay for S in a TMPRSS2-dependent manner using cell lines expressing Renilla luciferase (RL)-based split reporter proteins. S was stably expressed in the effector cells, and the corresponding receptor for S, CD26, was stably coexpressed with TMPRSS2 in the target cells. Membrane fusion between these effector and target cells was quantitatively measured by determining the RL activity. The assay was optimized for a 384-well format, and nafamostat, a serine protease inhibitor, was identified as a potent inhibitor of S-mediated membrane fusion in a screening of about 1,000 drugs approved for use by the U.S. Food and Drug Administration. Nafamostat also blocked MERS-CoV infection in vitro. Our assay has the potential to facilitate the discovery of new inhibitors of membrane fusion of MERS-CoV as well as other viruses that rely on the activity of TMPRSS2.",,"['Yamamoto, Mizuki', 'Matsuyama, Shutoku', 'Li, Xiao', 'Takeda, Makoto', 'Kawaguchi, Yasushi', 'Inoue, Jun-ichiro', 'Matsuda, Zene']",,,,
,PMC,In vitro exposure system for study of aerosolized influenza virus,http://dx.doi.org/10.1016/j.virol.2016.10.007,PMC5221479,,,"Infection of adherent cell monolayers using a liquid inoculum represents an established method to reliably and quantitatively study virus infection, but poorly recapitulates the exposure and infection of cells in the respiratory tract that occurs during infection with aerosolized pathogens. To better simulate natural infection in vitro, we adapted a system that generates viral aerosols similar to those exhaled by infected humans to the inoculation of epithelial cell monolayers. Procedures for cellular infection and calculation of exposure dose were developed and tested using viruses characterized by distinct transmission and pathogenicity phenotypes: an HPAI H5N1, an LPAI H7N9, and a seasonal H3N2 virus. While all three aerosolized viruses were highly infectious in a bronchial epithelial cell line (Calu-3) cultured submerged in media, differences between the viruses were observed in primary human alveolar epithelial cells and in Calu-3 cells cultured at air-liquid interface. This system provides a novel enhancement to traditional in vitro experiments, particularly those focused on the early stages of infection.",,"['Creager, Hannah M.', 'Zeng, Hui', 'Pulit-Penaloza, Joanna A.', 'Maines, Taronna R.', 'Tumpey, Terrence M.', 'Belser, Jessica A.']",,,,
,PMC,Sex in a test tube: testing the benefits of in vitro recombination,http://dx.doi.org/10.1098/rstb.2015.0529,PMC5031614,,,"The origin and evolution of sex, and the associated role of recombination, present a major problem in biology. Sex typically involves recombination of closely related DNA or RNA sequences, which is fundamentally a random process that creates but also breaks up beneficial allele combinations. Directed evolution experiments, which combine in vitro mutation and recombination protocols with in vitro or in vivo selection, have proved to be an effective approach for improving functionality of nucleic acids and enzymes. As this approach allows extreme control over evolutionary conditions and parameters, it also facilitates the detection of small or position-specific recombination benefits and benefits associated with recombination between highly divergent genotypes. Yet, in vitro approaches have been largely exploratory and motivated by obtaining improved end products rather than testing hypotheses of recombination benefits. Here, we review the various experimental systems and approaches used by in vitro studies of recombination, discuss what they say about the evolutionary role of recombination, and sketch their potential for addressing extant questions about the evolutionary role of sex and recombination, in particular on complex fitness landscapes. We also review recent insights into the role of ‘extracellular recombination’ during the origin of life. This article is part of the themed issue ‘Weird sex: the underappreciated diversity of sexual reproduction’.",,"['Pesce, Diego', 'Lehman, Niles', 'de Visser, J. Arjan G. M.']",,,,
,PMC,Recent trends on hydrogels based drug delivery systems for infectious diseases,http://dx.doi.org/10.1039/c6bm00276e,PMC5162423,,,"For centuries, the rapid spread and cure of infectious diseases have been a major concern to the progress and survival of humans. These diseases are the global burden and the prominent cause for the worldwide deaths and disability. Nanomedicine has emerged as the most excellent tool to eradicate and halt their spread. Various nanoformulations (NFs) using advanced nanotechnology are in demand. Recently, hydrogel and nanogel based drug delivery devices poses new prospects to simulate the natural intelligence of various biological systems. Owing to their unique porous interpenetrating network design, hydrophobic drug incorporation and stimulus sensitivity hydrogels owe excellent potential as targeted drug delivery system. Present review is an attempt to highlight the recent trends of hydrogel based drug delivery systems for the delivery of therapeutic agents and diagnostics for the major infectious diseases including Acquired immune deficiency syndrome (AIDS), Malaria, Tuberculosis, Influenza and Ebola. Future prospective and challenges are also briefed.",,"['Vashist, Arti', 'Kaushik, Ajeet', 'Vashist, Atul', 'Jayant, Rahul Dev', 'Tomitaka, Asahi', 'Ahmad, Sharif', 'Gupta, Y. K.', 'Nair, Madhavan']",,,,
,PMC,Updates in diagnosis and management of Ebola hemorrhagic fever,http://dx.doi.org/10.4103/1735-1995.192500,PMC5244689,28163730,CC BY-NC-SA,"Ebola hemorrhagic fever is a lethal viral disease transmitted by contact with infected people and animals. Ebola infection represents a worldwide health threat causing enormous mortality rates and fatal epidemics. Major concern is pilgrimage seasons with possible transmission to Middle East populations. In this review, we aim to shed light on Ebola hemorrhagic fever as regard: virology, transmission, biology, pathogenesis, clinical picture, and complications to get the best results for prevention and management. We also aim to guide future research to new therapeutic perspectives to precise targets. Our methodology was to review the literature extensively to make an overall view of the biology of Ebola virus infection, its serious health effects and possible therapeutic benefits using currently available remedies and future perspectives. Key findings in Ebola patients are fever, hepatic impairment, hepatocellular necrosis, lymphopenia (for T-lymphocyte and natural killer cells) with lymphocyte apoptosis, hemorrhagic manifestations, and complications. Pathogenesis in Ebola infection includes oxidative stress, immune suppression of both cell-mediated and humoral immunities, hepatic and adrenal impairment and failure, hemorrhagic fever, activation of deleterious inflammatory pathways, for example, tumor necrosis factor-related apoptosis-inducing ligand, and factor of apoptotic signal death receptor pathways causing lymphocyte depletion. Several inflammatory mediators and cytokines are involved in pathogenesis, for example, interleukin-2, 6, 8, and 10 and others. In conclusion, Ebola hemorrhagic fever is a serious fatal viral infection that can be prevented using strict health measures and can be treated to some extent using some currently available remedies. Newer treatment lines, for example, prophetic medicine remedies as nigella sativa may be promising.",2016 Oct 18,"['El Sayed, Salah Mohamed', 'Abdelrahman, Ali A.', 'Ozbak, Hani Adnan', 'Hemeg, Hassan Abdullah', 'Kheyami, Ali Mohammed', 'Rezk, Nasser', 'El-Ghoul, Mohamed Baioumy', 'Nabo, Manal Mohamed Helmy', 'Fathy, Yasser Mohamed']",J Res Med Sci,,,
,PMC,Crucial steps in the structure determination of a coronavirus spike glycoprotein using cryo‐electron microscopy,http://dx.doi.org/10.1002/pro.3048,PMC5192993,,,"The tremendous pandemic potential of coronaviruses was demonstrated twice in the last 15 years by two global outbreaks of deadly pneumonia. Entry of coronaviruses into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer carrying receptor‐binding and membrane fusion functions. Despite their biomedical importance, coronavirus S glycoproteins have proven difficult targets for structural characterization, precluding high‐resolution studies of the biologically relevant trimer. Recent technological developments in single particle cryo‐electron microscopy allowed us to determine the first structure of a coronavirus S glycoprotein trimer which provided a framework to understand the mechanisms of viral entry and suggested potential inhibition strategies for this family of viruses. Here, we describe the key factors that enabled this breakthrough.",,"['Walls, Alexandra', 'Tortorici, M. Alejandra', 'Bosch, Berend‐Jan', 'Frenz, Brandon', 'Rottier, Peter J. M.', 'DiMaio, Frank', 'Rey, Felix A.', 'Veesler, David']",,,,
,PMC,Hospital admissions for lower respiratory tract infections among infants in the Canadian Arctic: a cohort study,http://dx.doi.org/10.9778/cmajo.20150051,PMC5173479,,,"BACKGROUND: It is unknown whether this burden of disease of lower respiratory tract infections is comparable across the Canadian Arctic. The objectives of this surveillance study were to compare the rates of hospital admission for lower respiratory tract infection and the severity of infection across Arctic Canada, and to describe the responsible viruses. METHODS: We performed a prospective multicentre surveillance study of infants less than 1 year of age admitted in 2009 with lower respiratory tract infection to all hospitals (5 regional, 4 tertiary) in the Northwest Territories, Nunavut and Nunavik to assess for regional differences. Nasopharyngeal aspirates were processed by means of a polymerase chain reaction respiratory viral panel, testing for 20 respiratory viruses and influenza A (H1N1). The role of coinfection was assessed by means of regression analysis for length of stay (short: < 7 d; long: > 14 d). Outcomes compared included rates of lower respiratory tract infection, respiratory syncytial virus infection, transfer to tertiary hospital and severe lower respiratory tract infection (respiratory failure, intubation and mechanical ventilation, and/or cardiopulmonary resuscitation). RESULTS: There were 348 admissions for lower respiratory tract infection in the population of interest in 2009. Rates of admission per 1000 live births varied significantly, from 39 in the Northwest Territories to 456 in Nunavik (p < 0.001). The rates of tertiary admissions and severe lower respiratory tract infection per 1000 live births in the Northwest Territories were 5.6 and 1.4, respectively, compared to 55.9 and 17.1, respectively, in Nunavut and 52.0 and 20.0, respectively, in Nunavik (p ≤ 0.001). Respiratory syncytial virus was the most common virus identified (124 cases [41.6% of those tested]), and coinfection was detected in 51 cases (41.1%) of infection with this virus. Longer length of stay was associated with coinfection (odds ratio [OR] 2.64) and underlying risk factors (OR 4.39). Length of stay decreased by 32.2% for every 30-day increase in age (OR 0.68). INTERPRETATION: Nunavut and Nunavik have very elevated rates of lower respiratory tract infection, with severe outcomes. Respiratory syncytial virus was the most common virus identified, and coinfection was associated with longer length of stay. Targeted public health interventions are required to reduce the burden of disease for infants residing in these Arctic regions.",,"['Banerji, Anna', 'Panzov, Val', 'Young, Michael', 'Robinson, Joan', 'Lee, Bonita', 'Moraes, Theo', 'Mamdani, Muhammad', 'Giles, B. Louise', 'Jiang, Depeng', 'Bisson, Danny', 'Dennis, Marguerite', 'Morel, Johanne', 'Hall, Judith', 'Hui, Charles', 'Paes, Bosco', 'Mahony, James B.']",,,,
,PMC,Nasal decongestants in monotherapy for the common cold,http://dx.doi.org/10.1002/14651858.CD009612.pub2,PMC6461189,,,"BACKGROUND: Many treatments for the common cold exist and are sold over‐the‐counter. Nevertheless, evidence on the effectiveness and safety of nasal decongestants is limited. OBJECTIVES: To assess the efficacy, and short‐ and long‐term safety, of nasal decongestants used in monotherapy to alleviate symptoms of the common cold in adults and children. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 6, June 2016), which contains the Cochrane Acute Respiratory Infections (ARI) Specialised Register, MEDLINE (1946 to July 2016), Embase (2010 to 15 July 2016), CINAHL (1981 to 15 July 2016), LILACS (1982 to July 2016), Web of Science (1955 to July 2016) and clinical trials registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster‐RCTs investigating the effectiveness and adverse effects of nasal decongestants compared with placebo for treating the common cold in adults and children. We excluded quasi‐RCTs. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted and summarised data on subjective measures of nasal congestion, overall patient well‐being score, objective measures of nasal airway resistance, adverse effects and general recovery. One review author acted as arbiter in cases of disagreement. We categorised trials as single and multi‐dose and analysed data both separately and together. We also analysed studies using an oral or topical nasal decongestant separately and together. MAIN RESULTS: We included 15 trials with 1838 participants. Fourteen studies included adult participants only (aged 18 years and over). In six studies the intervention was a single dose and in nine studies multiple doses were used. Nine studies used pseudoephedrine and three studies used oxymetazoline. Other decongestants included phenylpropanolamine, norephedrine and xylometazoline. Phenylpropanolamine (or norephedrine) is no longer available on the market therefore we did not include the results of these studies in the meta‐analyses. Eleven studies used oral decongestants; four studies used topical decongestants. Participants were included after contracting the common cold. The duration of symptoms differed among studies; in 10 studies participants had symptoms for less than three days, in three studies symptoms were present for less than five days, one study counted the number of colds over one year, and one study experimentally induced the common cold. In the single‐dose studies, the effectiveness of a nasal decongestant was measured on the same day, whereas the follow‐up in multi‐dose studies ranged between one and 10 days. Most studies were conducted in university settings (N = eight), six at a specific university common cold centre. Three studies were conducted at a university in collaboration with a hospital and two in a hospital only setting. In two studies the setting was unclear. There were large differences in the reporting of outcomes and the reporting of methods in most studies was limited. Therefore, we judged most studies to be at low or unclear risk of bias. Pooling was possible for a limited number of studies only; measures of effect are expressed as standardised mean differences (SMDs). A positive SMD represents an improvement in congestion. There is no defined minimal clinically important difference for measures of subjective improvement in nasal congestion, therefore we used the SMDs as a guide to assess whether an effect was small (0.2 to 0.49), moderate (0.5 to 0.79) or large (≥ 0.8). Single‐dose decongestant versus placebo: 10 studies compared a single dose of nasal decongestant with placebo and their effectiveness was tested between 15 minutes and 10 hours after dosing. Seven of 10 studies reported subjective symptom scores for nasal congestion; none reported overall patient well‐being. However, pooling was not possible due to the large diversity in the measurement and reporting of symptoms of congestion. Two studies recorded adverse events. Both studies used an oral decongestant and each of them showed that there was no statistical difference between the number of adverse events in the treatment group versus the placebo group. Multi‐dose decongestant versus placebo: nine studies compared multiple doses of nasal decongestants with placebo, but only five reported on the primary outcome, subjective symptom scores for nasal congestion. Only one study used a topical decongestant; none reported overall patient well‐being. Subjective measures of congestion were significantly better for the treatment group compared with placebo approximately three hours after the last dose (SMD 0.49, 95% confidence interval (CI) 0.07 to 0.92; P = 0.02; GRADE: low‐quality evidence). However, the SMD of 0.49 only indicates a small clinical effect. Pooling was based on two studies, one oral and one topical, therefore we were unable to assess the effects of oral and topical decongestants separately. Seven studies reported adverse events (six oral and one topical decongestant); meta‐analysis showed that there was no statistical difference between the number of adverse events in the treatment group (125 per 1000) compared to the placebo group (126 per 1000). The odds ratio (OR) for adverse events in the treatment group was 0.98 (95% CI 0.68 to 1.40; P = 0.90; GRADE: low‐quality evidence). The results remained the same when we only considered studies using an oral decongestant (OR 0.95, 95% CI 0.65 to 1.39; P = 0.80; GRADE: low‐quality evidence). AUTHORS' CONCLUSIONS: We were unable to draw conclusions on the effectiveness of single‐dose nasal decongestants due to the limited evidence available. For multiple doses of nasal decongestants, the current evidence suggests that these may have a small positive effect on subjective measures of nasal congestion in adults with the common cold. However, the clinical relevance of this small effect is unknown and there is insufficient good‐quality evidence to draw any firm conclusions. Due to the small number of studies that used a topical nasal decongestant, we were also unable to draw conclusions on the effectiveness of oral versus topical decongestants. Nasal decongestants do not seem to increase the risk of adverse events in adults in the short term. The effectiveness and safety of nasal decongestants in children and the clinical relevance of their small effect in adults is yet to be determined.",,"['Deckx, Laura', 'De Sutter, An IM', 'Guo, Linda', 'Mir, Nabiel A', 'van Driel, Mieke L']",,,,
,PMC,"The Effect of Hospital Isolation Precautions on Patient Outcomes and Cost of Care: A Multi-Site, Retrospective, Propensity Score-Matched Cohort Study",http://dx.doi.org/10.1007/s11606-016-3862-4,PMC5330996,,,"BACKGROUND: Isolation precautions have negative effects on patient safety, psychological well-being, and healthcare worker contact. However, it is not known whether isolation precautions affect certain hospital-related outcomes. OBJECTIVE: To examine the effect of isolation precautions on hospital-related outcomes and cost of care. DESIGN: Retrospective, propensity-score matched cohort study of inpatients admitted to general internal medicine (GIM) services at three academic hospitals in Toronto, Ontario, Canada between January 2010 and December 2012. PARTICIPANTS: Adult (≥18 years of age) patients on isolation precautions for respiratory illnesses and methicillin-resistant Staphylococcus aureus (MRSA) were matched to controls based on propensity scores derived from nine covariates: age, sex, Resource Intensity Weight, number of hospital readmissions within 90 days, total length of stay for hospital admissions within 90 days, site of admission, month of isolation, year of isolation, and Case Mix Group. MAIN MEASURES: Thirty-day readmission rates and emergency department visits, hospital length of stay, expected length of stay, adverse events, in-hospital mortality, patient complaints, and cost of care in Canadian doll ars (CAD). KEY RESULTS: A total of 17,649 non-isolated patients were admitted to the participating hospitals during the study period. We identified 1506 patients isolated for respiratory illnesses and 745 patients isolated for MRSA. Compared to non-isolated individuals, those on isolation precautions for respiratory illnesses stayed 17 % longer (95 % CI: 9 %, 25 %), stayed 9 % longer than expected (95 % CI: 3 %, 15 %), and had 23 % higher cost of care (95 % CI: 14 %, 32 %). Patients isolated for MRSA had similar outcomes, but they also had a 4.4 % higher (95 % CI: 1.4 %, 7.3 %) rate of readmission to hospital within 30 days. CONCLUSIONS: Isolation precautions are associated with adverse effects which may result in poorer hospital outcomes. Balancing the benefits for the many with the harms to the few will be a future challenge.",,"['Tran, Kim', 'Bell, Chaim', 'Stall, Nathan', 'Tomlinson, George', 'McGeer, Allison', 'Morris, Andrew', 'Gardam, Michael', 'Abrams, Howard B.']",,,,
,PMC,Estimating age-specific reproductive numbers—A comparison of methods,http://dx.doi.org/10.1177/0962280216673676,PMC5643256,,,"Large outbreaks, such as those caused by influenza, put a strain on resources necessary for their control. In particular, children have been shown to play a key role in influenza transmission during recent outbreaks, and targeted interventions, such as school closures, could positively impact the course of emerging epidemics. As an outbreak is unfolding, it is important to be able to estimate reproductive numbers that incorporate this heterogeneity and to use surveillance data that is routinely collected to more effectively target interventions and obtain an accurate understanding of transmission dynamics. There are a growing number of methods that estimate age-group specific reproductive numbers with limited data that build on methods assuming a homogenously mixing population. In this article, we introduce a new approach that is flexible and improves on many aspects of existing methods. We apply this method to influenza data from two outbreaks, the 2009 H1N1 outbreaks in South Africa and Japan, to estimate age-group specific reproductive numbers and compare it to three other methods that also use existing data from social mixing surveys to quantify contact rates among different age groups. In this exercise, all estimates of the reproductive numbers for children exceeded the critical threshold of one and in most cases exceeded those of adults. We introduce a flexible new method to estimate reproductive numbers that describe heterogeneity in the population.",,"['Moser, Carlee B', 'White, Laura F']",,,,
,PMC,Steady-state kinetic studies reveal that the anti-cancer target Ubiquitin-Specific Protease 17 (USP17) is a highly efficient deubiquitinating enzyme,http://dx.doi.org/10.1016/j.abb.2016.10.008,PMC5868344,,,[Image: see text],,"['Hjortland, Nicole M.', 'Mesecar, Andrew D.']",,,,
,PMC,Neuropilin-1 modulates interferon-γ-stimulated signaling in brain microvascular endothelial cells,http://dx.doi.org/10.1242/jcs.190702,PMC5087664,,,"Inflammatory response of blood–brain barrier (BBB) endothelial cells plays an important role in pathogenesis of many central nervous system inflammatory diseases, including multiple sclerosis; however, the molecular mechanism mediating BBB endothelial cell inflammatory response remains unclear. In this study, we first observed that knockdown of neuropilin-1 (NRP1), a co-receptor of several structurally diverse ligands, suppressed interferon-γ (IFNγ)-induced C-X-C motif chemokine 10 expression and activation of STAT1 in brain microvascular endothelial cells in a Rac1-dependent manner. Moreover, endothelial-specific NRP1-knockout mice, VECadherin-Cre-ERT2/NRP1(flox/flox) mice, showed attenuated disease progression during experimental autoimmune encephalomyelitis, a mouse neuroinflammatory disease model. Detailed analysis utilizing histological staining, quantitative PCR, flow cytometry and magnetic resonance imaging demonstrated that deletion of endothelial NRP1 suppressed neuron demyelination, altered lymphocyte infiltration, preserved BBB function and decreased activation of the STAT1–CXCL10 pathway. Furthermore, increased expression of NRP1 was observed in endothelial cells of acute multiple sclerosis lesions. Our data identify a new molecular mechanism of brain microvascular endothelial inflammatory response through NRP1–IFNγ crosstalk that could be a potential target for intervention of endothelial cell dysfunction in neuroinflammatory diseases.",,"['Wang, Ying', 'Cao, Ying', 'Mangalam, Ashutosh K.', 'Guo, Yong', 'LaFrance-Corey, Reghann G.', 'Gamez, Jeffrey D.', 'Atanga, Pascal Aliihnui', 'Clarkson, Benjamin D.', 'Zhang, Yuebo', 'Wang, Enfeng', 'Angom, Ramcharan Singh', 'Dutta, Kirthica', 'Ji, Baoan', 'Pirko, Istvan', 'Lucchinetti, Claudia F.', 'Howe, Charles L.', 'Mukhopadhyay, Debabrata']",,,,
,PMC,A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection,http://dx.doi.org/10.1016/j.virol.2016.10.005,PMC5167628,,,"Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was first identified in 2012, and it continues to threaten human health worldwide. No MERS vaccines are licensed for human use, reinforcing the urgency to develop safe and efficacious vaccines to prevent MERS. MERS-CoV spike protein forms a trimer, and its receptor-binding domain (RBD) serves as a vaccine target. Nevertheless, the protective efficacy of RBD in its native trimeric form has never been evaluated. In this study, a trimeric protein, RBD-Fd, was generated by fusing RBD with foldon trimerization motif. It bound strongly to the receptor of MERS-CoV, dipeptidyl peptidase 4 (DPP4), and elicited robust RBD-specific neutralizing antibodies in mice, maintaining long-term neutralizing activity against MERS-CoV infection. RBD-Fd potently protected hDPP4 transgenic mice from lethal MERS-CoV challenge. These results suggest that MERS-CoV RBD in its trimeric form maintains native conformation and induces protective neutralizing antibodies, making it a candidate for further therapeutic development.",,"['Tai, Wanbo', 'Zhao, Guangyu', 'Sun, Shihun', 'Guo, Yan', 'Wang, Yufei', 'Tao, Xinrong', 'Tseng, Chien-Te K', 'Li, Fang', 'Jiang, Shibo', 'Du, Lanying', 'Zhou, Yusen']",,,,
,PMC,Enterovirus 71 2B Induces Cell Apoptosis by Directly Inducing the Conformational Activation of the Proapoptotic Protein Bax,http://dx.doi.org/10.1128/JVI.01499-16,PMC5068536,,,"To survive and replicate within a host, many viruses have evolved strategies that target crucial components within the apoptotic cascade, leading to either inhibition or induction of cell apoptosis. Enterovirus 71 (EV71) infections have been demonstrated to impact the mitochondrial apoptotic pathway and induce apoptosis in many cell lines. However, the detailed mechanism of EV71-induced apoptosis remains to be elucidated. In this study, we report that EV71 2B protein (2B) localized to the mitochondria and induced cell apoptosis by interacting directly with and activating the proapoptotic protein Bax. 2B recruited Bax to the mitochondria and induced Bax conformational activation. In addition, mitochondria isolated from 2B-expressing cells that were treated with a recombinant Bax showed increased Bax interaction and cytochrome c (Cyt c) release. Importantly, apoptosis in cells with either EV71 infection or 2B expression was dramatically reduced in Bax knockdown cells but not in Bak knockdown cells, suggesting that Bax played a pivotal role in EV71- or 2B-induced apoptosis. Further studies indicate that a hydrophobic region of 18 amino acids (aa) in the C-terminal region of 2B (aa 63 to 80) was responsible for the location of 2B in the mitochondria. A hydrophilic region of 14 aa in the N-terminal region of 2B was functional in Bax interaction and its subsequent activation. Moreover, overexpression of the antiapoptotic protein Bcl-X(L) abrogates 2B-induced release of Cyt c and caspase activation. Therefore, this study provides direct evidence that EV71 2B induces cell apoptosis and impacts the mitochondrial apoptotic pathway by directly modulating the redistribution and activation of proapoptotic protein Bax. IMPORTANCE EV71 infections are usually accompanied by severe neurological complications. It has also been postulated that the induction of cell apoptosis resulting from tissue damage is a possible process of EV71-related pathogenesis. In this study, we report that EV71 2B protein (2B) localized to the mitochondria and induced cell apoptosis by interacting directly with and activating the proapoptotic protein Bax. This study provides evidence that EV71 induces cell apoptosis by modulating Bax activation and reveals important clues regarding the mechanism of Cyt c release and mitochondrial permeabilization during EV71 infection.",,"['Cong, Haolong', 'Du, Ning', 'Yang, Yang', 'Song, Lei', 'Zhang, Wenliang', 'Tien, Po']",,,,
,PMC,Antagonism of RNase L Is Required for Murine Coronavirus Replication in Kupffer Cells and Liver Sinusoidal Endothelial Cells but Not in Hepatocytes,http://dx.doi.org/10.1128/JVI.01423-16,PMC5068532,,,"Mouse hepatitis virus strain A59 infection of mice is a useful tool for studying virus-host interaction during hepatitis development. The NS2(H126R) mutant is attenuated in liver replication due to loss of phosphodiesterase activity, which the wild-type (WT) virus uses to block the 2′,5′-oligoadenylate synthetase (OAS)-RNase L (RNase L) antiviral pathway. The activation of RNase L by NS2(H126R) is cell type dependent and correlates with high basal expression levels of OAS, as found in myeloid cells. We tested the hypothesis that the resident liver macrophages, Kupffer cells (KC), represent the cell type most likely to restrict NS2(H126R) and prevent hepatitis. As found previously, A59 and NS2(H126R) replicate similarly in hepatocytes and neither activates RNase L, as assessed by an rRNA degradation assay. In contrast, in KC, A59 exhibited a 100-fold-higher titer than NS2(H126R) and NS2(H126R) induced rRNA degradation. Interestingly, in liver sinusoidal endothelial cells (LSEC), the cells that form a barrier between blood and liver parenchymal cells, NS2(H126R) activates RNase L, which limits viral replication. Similar growth kinetics were observed for the two viruses in KC and LSEC from RNase L(−/−) mice, demonstrating that both use RNase L to limit NS2(H126R) replication. Depletion of KC by gadolinium(III) chloride or of LSEC by cyclophosphamide partially restores liver replication of NS2(H126R), leading to hepatitis. Thus, during mouse hepatitis virus (MHV) infection, hepatitis, which damages the parenchyma, is prevented by RNase L activity in both KC and LSEC but not in hepatocytes. This may be explained by the undetectable levels of RNase L as well as by the OASs expressed in hepatocytes. IMPORTANCE Mouse hepatitis virus infection of mice provides a useful tool for studying virus-host interactions during hepatitis development. The NS2(H126R) mutant is attenuated in liver replication due to loss of phosphodiesterase activity, by which the wild-type virus blocks the potent OAS-RNase L antiviral pathway. RNase L activation by NS2(H126R) is cell type dependent and correlates with high basal expression levels of OAS, as found in myeloid cells. We showed that the hepatocytes that comprise the liver parenchyma do not activate RNase L when infected with NS2(H126R) or restrict replication. However, both Kupffer cells (KC) (i.e., the liver-resident macrophages) and the liver sinusoidal endothelial cells (LSEC) which line the sinusoids activate RNase L in response to NS2(H126R). These data suggest that KC and LSEC prevent viral spread into the parenchyma, preventing hepatitis. Furthermore, hepatocytes express undetectable levels of OASs and RNase L, which likely explains the lack of RNase L activation during NS2(H126R) infection.",,"['Li, Yize', 'Weiss, Susan R.']",,,,
,PMC,Inhibition of Polyamine Biosynthesis Is a Broad-Spectrum Strategy against RNA Viruses,http://dx.doi.org/10.1128/JVI.01347-16,PMC5068521,,,"RNA viruses present an extraordinary threat to human health, given their sudden and unpredictable appearance, the potential for rapid spread among the human population, and their ability to evolve resistance to antiviral therapies. The recent emergence of chikungunya virus, Zika virus, and Ebola virus highlights the struggles to contain outbreaks. A significant hurdle is the availability of antivirals to treat the infected or protect at-risk populations. While several compounds show promise in vitro and in vivo, these outbreaks underscore the need to accelerate drug discovery. The replication of several viruses has been described to rely on host polyamines, small and abundant positively charged molecules found in the cell. Here, we describe the antiviral effects of two molecules that alter polyamine levels: difluoromethylornithine (DFMO; also called eflornithine), which is a suicide inhibitor of ornithine decarboxylase 1 (ODC1), and diethylnorspermine (DENSpm), an activator of spermidine/spermine N(1)-acetyltransferase (SAT1). We show that reducing polyamine levels has a negative effect on diverse RNA viruses, including several viruses involved in recent outbreaks, in vitro and in vivo. These findings highlight the importance of the polyamine biosynthetic pathway to viral replication, as well as its potential as a target in the development of further antivirals or currently available molecules, such as DFMO. IMPORTANCE RNA viruses present a significant hazard to human health, and combatting these viruses requires the exploration of new avenues for targeting viral replication. Polyamines, small positively charged molecules within the cell, have been demonstrated to facilitate infection for a few different viruses. Our study demonstrates that diverse RNA viruses rely on the polyamine pathway for replication and highlights polyamine biosynthesis as a promising drug target.",,"['Mounce, Bryan C.', 'Cesaro, Teresa', 'Moratorio, Gonzalo', 'Hooikaas, Peter Jan', 'Yakovleva, Anna', 'Werneke, Scott W.', 'Smith, Everett Clinton', 'Poirier, Enzo Z.', 'Simon-Loriere, Etienne', 'Prot, Matthieu', 'Tamietti, Carole', 'Vitry, Sandrine', 'Volle, Romain', 'Khou, Cécile', 'Frenkiel, Marie-Pascale', 'Sakuntabhai, Anavaj', 'Delpeyroux, Francis', 'Pardigon, Nathalie', 'Flamand, Marie', 'Barba-Spaeth, Giovanna', 'Lafon, Monique', 'Denison, Mark R.', 'Albert, Matthew L.', 'Vignuzzi, Marco']",,,,
,PMC,Intracerebral Inoculation of Mouse-Passaged Saffold Virus Type 3 Affects Cerebellar Development in Neonatal Mice,http://dx.doi.org/10.1128/JVI.00864-16,PMC5068506,,,"Saffold virus (SAFV), a human cardiovirus, is occasionally detected in infants with neurological disorders, including meningitis and cerebellitis. We recently reported that SAFV type 3 isolates infect cerebellar glial cells, but not large neurons, in mice. However, the impact of this infection remained unclear. Here, we determined the neuropathogenesis of SAFV type 3 in the cerebella of neonatal ddY mice by using SAFV passaged in the cerebella of neonatal BALB/c mice. The virus titer in the cerebellum increased following the inoculation of each of five passaged strains. The fifth passaged strain harbored amino acid substitutions in the VP2 (H160R and Q239R) and VP3 (K62M) capsid proteins. Molecular modeling of the capsid proteins suggested that the VP2-H160R and VP3-K62M mutations alter the structural dynamics of the receptor binding surface via the formation of a novel hydrophobic interaction between the VP2 puff B and VP3 knob regions. Compared with the original strain, the passaged strain showed altered growth characteristics in human-derived astroglial cell lines and greater replication in the brains of neonatal mice. In addition, the passaged strain was more neurovirulent than the original strain, while both strains infected astroglial and neural progenitor cells in the mouse brain. Intracerebral inoculation of either the original or the passaged strain affected brain Purkinje cell dendrites, and a high titer of the passaged strain induced cerebellar hypoplasia in neonatal mice. Thus, infection by mouse-passaged SAFV affected cerebellar development in neonatal mice. This animal model contributes to the understanding of the neuropathogenicity of SAFV infections in infants. IMPORTANCE Saffold virus (SAFV) is a candidate neuropathogenic agent in infants and children, but the neuropathogenicity of the virus has not been fully elucidated. Recently, we evaluated the pathogenicity of two clinical SAFV isolates in mice. Similar to other neurotropic picornaviruses, these isolates showed mild infectivity of glial and neural progenitor cells, but not of large neurons, in the cerebellum. However, the outcome of this viral infection in the cerebellum has not been clarified. Here, we examined the tropism of SAFV in the cerebellum. We obtained an in vivo-passaged strain from the cerebella of neonatal mice and examined its genome and its neurovirulence in the neonatal mouse brain. The passaged virus showed high infectivity and neurovirulence in the brain, especially the cerebellum, and affected cerebellar development. This unique neonatal mouse model will be helpful for elucidating the neuropathogenesis of SAFV infections occurring early in life.",,"['Kotani, Osamu', 'Suzuki, Tadaki', 'Yokoyama, Masaru', 'Iwata-Yoshikawa, Naoko', 'Nakajima, Noriko', 'Sato, Hironori', 'Hasegawa, Hideki', 'Taguchi, Fumihiro', 'Shimizu, Hiroyuki', 'Nagata, Noriyo']",,,,
,PMC,Investigating Rare Risk Factors for Nipah Virus in Bangladesh: 2001–2012,http://dx.doi.org/10.1007/s10393-016-1166-0,PMC5164848,,,"Human Nipah encephalitis outbreaks have been identified almost yearly in Bangladesh since 2001. Though raw date palm sap consumption and person-to-person contact are recognized as major transmission pathways, alternative pathways of transmission are plausible and may not have been identified due to limited statistical power in each outbreak. We conducted a risk factor analysis using all 157 cases and 632 controls surveyed in previous investigations during 2004–2012 to identify exposures independently associated with Nipah, since date palm sap was first asked about as an exposure in 2004. To further explore possible rare exposures, we also conducted in-depth interviews with all cases, or proxies, since 2001 that reported no exposure to date palm sap or contact with another case. Cases were 4.9 (95% 3.2–7.7) times more likely to consume raw date palm sap and 7.3 (95% 4.0–13.4) times more likely to have contact with a Nipah case than controls. In-depth interviews revealed that 39/182 (21%) of Nipah cases reporting neither date palm sap consumption nor contact with another case were misclassified. Prevention efforts should be focused on interventions to interrupt transmission through date palm sap consumption and person-to-person contact. Furthermore, pooling outbreak investigation data is a good method for assessing rare exposures.",,"['Hegde, Sonia T.', 'Sazzad, Hossain M. S.', 'Hossain, M. Jahangir', 'Alam, Mahbub-Ul', 'Kenah, Eben', 'Daszak, Peter', 'Rollin, Pierre', 'Rahman, Mahmudur', 'Luby, Stephen P.', 'Gurley, Emily S.']",,,,
,PMC,The Evolution of Ebola virus: Insights from the 2013–2016 Epidemic,http://dx.doi.org/10.1038/nature19790,PMC5580494,,,"The 2013–2016 epidemic of Ebola virus disease in West Africa was of unprecedented magnitude and changed our perspective on this lethal but sporadically emerging virus. This outbreak also marked the beginning of large-scale real-time molecular epidemiology. Herein, we show how evolutionary analyses of Ebola virus genome sequences provided key insights into virus origins, evolution, and spread during the epidemic. We provide basic scientists, epidemiologists, medical practitioners, and other outbreak responders with an enhanced understanding of the utility and limitations of pathogen genomic sequencing. This will be crucially important in our attempts to track and control future infectious disease outbreaks.",,"['Holmes, Edward C.', 'Dudas, Gytis', 'Rambaut, Andrew', 'Andersen, Kristian G.']",,,,
,PMC,The Promise of Electronic Case Reporting,http://dx.doi.org/10.1177/0033354916670871,PMC5230835,,,,,"['Mac Kenzie, William R.', 'Davidson, Arthur J.', 'Wiesenthal, Andrew', 'Engel, Jeffrey P.', 'Turner, Kathryn', 'Conn, Laura', 'Becker, Scott J.', 'Moffatt, Sharon', 'Groseclose, Samuel L.', 'Jellison, Jim', 'Stinn, John', 'Garrett, Nedra Y.', 'Helmus, Lesliann', 'Harmon, Bob', 'Richards, Chesley L.', 'Lumpkin, John R.', 'Iademarco, Michael F.']",,,,
,PMC,Functional Motifs Responsible for Human Metapneumovirus M2-2-mediated Innate Immune Evasion,http://dx.doi.org/10.1016/j.virol.2016.09.026,PMC5102771,,,"Human metapneumovirus (hMPV) is a major cause of lower respiratory infection in young children. Repeated infections occur throughout life, but its immune evasion mechanisms are largely unknown. We recently found that hMPV M2-2 protein elicits immune evasion by targeting mitochondrial antiviral-signaling protein (MAVS), an antiviral signaling molecule. However, the molecular mechanisms underlying such inhibition are not known. Our mutagenesis studies revealed that PDZ-binding motifs, 29-DEMI-32 and 39-KEALSDGI-46, located in an immune inhibitory region of M2-2, are responsible for M2-2-mediated immune evasion. We also found both motifs prevent TRAF5 and TRAF6, the MAVS downstream adaptors, to be recruited to MAVS, while the motif 39-KEALSDGI-46 also blocks TRAF3 migrating to MAVS. In parallel, these TRAFs are important in activating transcription factors NF-kB and/or IRF-3 by hMPV. Our findings collectively demonstrate that M2-2 uses its PDZ motifs to launch the hMPV immune evasion through blocking the interaction of MAVS and its downstream TRAFs.",,"['Chen, Yu', 'Deng, Xiaoling', 'Deng, Junfang', 'Zhou, Jiehua', 'Ren, Yuping', 'Liu, Shengxuan', 'Prusak, Deborah J.', 'Wood, Thomas G.', 'Bao, Xiaoyong']",,,,
,PMC,"Pathogen–Host Defense in the Evolution of Depression: Insights into Epidemiology, Genetics, Bioregional Differences and Female Preponderance",http://dx.doi.org/10.1038/npp.2016.194,PMC5143499,,,"Significant attention has been paid to the potential adaptive value of depression as it relates to interactions with people in the social world. However, in this review, we outline the rationale of why certain features of depression including its environmental and genetic risk factors, its association with the acute phase response and its age of onset and female preponderance appear to have evolved from human interactions with pathogens in the microbial world. Approaching the relationship between inflammation and depression from this evolutionary perspective yields a number of insights that may reveal important clues regarding the origin and epidemiology of the disorder as well as the persistence of its risk alleles in the modern human genome.",,"['Raison, Charles L', 'Miller, Andrew H']",,,,
,PMC,Positive selection of the TRIM family regulatory region in primate genomes,http://dx.doi.org/10.1098/rspb.2016.1602,PMC5069514,,,"Viral selection pressure has acted on restriction factors that play an important role in the innate immune system by inhibiting the replication of viruses during primate evolution. Tripartite motif-containing (TRIM) family members are some of these restriction factors. It is becoming increasingly clear that gene expression differences, rather than protein-coding regions changes, could play a vital role in the anti-retroviral immune mechanism. Increasingly, recent studies have created genome-scale catalogues of DNase I hypersensitive sites (DHSs), which demark potentially functional regulatory DNA. To improve our understanding of the molecular evolution mechanism of antiviral differences between species, we leveraged 14 130 DHSs derived from 145 cell types to characterize the regulatory landscape of the TRIM region. Subsequently, we compared the alignments of the DHSs across six primates and found 375 DHSs that are conserved in non-human primates but exhibit significantly accelerated rates of evolution in the human lineage (haDHSs). Furthermore, we discovered 31 human-specific potential transcription factor motifs within haDHSs, including the KROX and SP1, that both interact with HIV-1. Importantly, the corresponding haDHS was correlated with antiviral factor TRIM23. Thus, our results suggested that some viruses may contribute, through regulatory DNA differences, to organismal evolution by mediating TRIM gene expression to escape immune surveillance.",,"['He, Dan-Dan', 'Lu, Yueer', 'Gittelman, Rachel', 'Jin, Yabin', 'Ling, Fei', 'Joshua, Akey']",,,,
,PMC,Data-driven outbreak forecasting with a simple nonlinear growth model,http://dx.doi.org/10.1016/j.epidem.2016.10.002,PMC5159251,,,"Recent events have thrown the spotlight on infectious disease outbreak response. We developed a data-driven method, EpiGro, which can be applied to cumulative case reports to estimate the order of magnitude of the duration, peak and ultimate size of an ongoing outbreak. It is based on a surprisingly simple mathematical property of many epidemiological data sets, does not require knowledge or estimation of disease transmission parameters, is robust to noise and to small data sets, and runs quickly due to its mathematical simplicity. Using data from historic and ongoing epidemics, we present the model. We also provide modeling considerations that justify this approach and discuss its limitations. In the absence of other information or in conjunction with other models, EpiGro may be useful to public health responders.",,"['Lega, Joceline', 'Brown, Heidi E.']",,,,
,PMC,Cell Entry of Porcine Epidemic Diarrhea Coronavirus Is Activated by Lysosomal Proteases,http://dx.doi.org/10.1074/jbc.M116.740746,PMC5114425,,,"Porcine epidemic diarrhea coronavirus (PEDV) is currently devastating the United States pork industry by causing an 80–100% fatality rate in infected piglets. Coronavirus spike proteins mediate virus entry into cells, a process that requires the spike proteins to be proteolytically activated. It has been a conundrum which proteases activate PEDV entry. Here we systematically investigated the roles of different proteases in PEDV entry using pseudovirus entry, biochemical, and live virus infection assays. We found that the PEDV spike is activated by lysosomal cysteine proteases but not proprotein convertases or cell surface serine proteases. Extracellular trypsin activates PEDV entry when lysosomal cysteine proteases are inhibited. We further pinpointed cathepsin L and cathepsin B as the lysosomal cysteine proteases that activate the PEDV spike. These results advance our understanding of the molecular mechanism for PEDV entry and identify potential antiviral targets for curbing the spread of PEDV.",,"['Liu, Chang', 'Ma, Yuanmei', 'Yang, Yang', 'Zheng, Yuan', 'Shang, Jian', 'Zhou, Yusen', 'Jiang, Shibo', 'Du, Lanying', 'Li, Jianrong', 'Li, Fang']",,,,
,PMC,Proteolytic processing of Middle East respiratory syndrome coronavirus spikes expands virus tropism,http://dx.doi.org/10.1073/pnas.1608147113,PMC5086990,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) infects humans from zoonotic sources and causes severe pulmonary disease. Virions require spike (S) glycoproteins for binding to cell receptors and for catalyzing virus–cell membrane fusion. Fusion occurs only after S proteins are cleaved sequentially, first during their secretion through the exocytic organelles of virus-producing cells, and second after virus binding to target-cell receptors. To more precisely determine how sequential proteolysis contributes to CoV infection, we introduced S mutations obstructing the first cleavages. These mutations severely compromised MERS-CoV infection into human lung-derived cells, but had little effect on infection into several other cell types. These cell type-specific requirements for proteolysis correlated with S conformations during cell entry. Without the first cleavages, S proteins resisted cell receptor-induced conformational changes, which restricted the second, fusion-activating cleavages. Consistent with these findings, precleaved MERS viruses used receptor-proximal, cell-surface proteases to effect the second fusion-activating cleavages during cell entry, whereas the more rigid uncleaved MERS viruses trafficked past these cell-surface proteases and into endosomes. Uncleaved viruses were less infectious to human airway epithelial and Calu3 cell cultures because they lacked sufficient endosomal fusion-activating proteases. Thus, by sensitizing viruses to receptor-induced conformational changes, the first S cleavages expand virus tropism to cell types that are relevant to lung infection, and therefore may be significant determinants of MERS-CoV virulence.",,"['Park, Jung-Eun', 'Li, Kun', 'Barlan, Arlene', 'Fehr, Anthony R.', 'Perlman, Stanley', 'McCray, Paul B.', 'Gallagher, Tom']",,,,
,PMC,Emerging connections between RNA and autophagy,http://dx.doi.org/10.1080/15548627.2016.1222992,PMC5240835,,,"Macroautophagy/autophagy is a key catabolic process, essential for maintaining cellular homeostasis and survival through the removal and recycling of unwanted cellular material. Emerging evidence has revealed intricate connections between the RNA and autophagy research fields. While a majority of studies have focused on protein, lipid and carbohydrate catabolism via autophagy, accumulating data supports the view that several types of RNA and associated ribonucleoprotein complexes are specifically recruited to phagophores (precursors to autophagosomes) and subsequently degraded in the lysosome/vacuole. Moreover, recent studies have revealed a substantial number of novel autophagy regulators with RNA-related functions, indicating roles for RNA and associated proteins not only as cargo, but also as regulators of this process. In this review, we discuss widespread evidence of RNA catabolism via autophagy in yeast, plants and animals, reviewing the molecular mechanisms and biological importance in normal physiology, stress and disease. In addition, we explore emerging evidence of core autophagy regulation mediated by RNA-binding proteins and noncoding RNAs, and point to gaps in our current knowledge of the connection between RNA and autophagy. Finally, we discuss the pathological implications of RNA-protein aggregation, primarily in the context of neurodegenerative disease.",,"['Frankel, Lisa B.', 'Lubas, Michal', 'Lund, Anders H.']",,,,
,PMC,Tuberculous meningitis in an immunocompetent male complicated by hydrocephalus,http://dx.doi.org/10.1136/bcr-2015-213916,PMC5073708,,,"A 39-year-old man, born in India but resident in the UK for 10 years, was travelling in America when he became feverish with an altered mentation. He reported a 10-day history of fever, photophobia, headache and fatigue. His medical history included hypothyroidism and migraine. He was a non-smoker, did not consume alcohol and denied a history of drug use. He was transferred to the emergency department. Laboratory investigations confirmed hyponatraemia (sodium 128 mmol/L). A chest radiograph confirmed no focal consolidation. Further investigation with a CT brain was unremarkable. A lumbar puncture was suggestive of viral meningitis, with a raised white cell count, lymphocytosis, high protein and low glucose. His PCR was negative for enterovirus and herpes simplex virus. Further investigation with a CT thorax, abdomen and pelvis demonstrated bilateral upper-lobe infiltrations. A bronchoalveolar lavage was negative for acid alcohol fast bacilli (AAFB). A diagnosis of tuberculous meningitis was rendered following a repeat lumbar puncture. Gram stain revealed AAFB and PCR was also positive. He started antitubercular treatment and corticosteroids. A repeat CT brain demonstrated ventriculomegaly, suggestive of hydrocephalus and an MRI head revealed likely communicating hydrocephalus with basilar enhancement. He was repatriated to the UK. Eleven days post transfer, he became acutely confused and required external ventricular drain insertion. After surgical management of his hydrocephalus, there was no further neurological deterioration. He remains committed to his neurorehabilitation.",,"['Dunphy, Louise', 'Shetty, Prashanth', 'Randhawa, Rabinder', 'Rani, Kharil Amir', 'Duodu, Yaw']",,,,
,PMC,Estimating infectious disease transmission distances using the overall distribution of cases,http://dx.doi.org/10.1016/j.epidem.2016.10.001,PMC5159225,,,"The average spatial distance between transmission-linked cases is a fundamental property of infectious disease dispersal. However, the distance between a case and their infector is rarely measurable. Contact-tracing investigations are resource intensive or even impossible, particularly when only a subset of cases are detected. Here, we developed an approach that uses onset dates, the generation time distribution and location information to estimate the mean transmission distance. We tested our method using outbreak simulations. We then applied it to the 2001 foot-and-mouth outbreak in Cumbria, UK, and compared our results to contact-tracing activities. In simulations with a true mean distance of 106m, the average mean distance estimated was 109m when cases were fully observed (95% range of 71–142). Estimates remained consistent with the true mean distance when only five percent of cases were observed, (average estimate of 128m, 95% range 87–165). Estimates were robust to spatial heterogeneity in the underlying population. We estimated that both the mean and the standard deviation of the transmission distance during the 2001 foot-and-mouth outbreak was 8.9km (95% CI: 8.4km-9.7km). Contact-tracing activities found similar values of 6.3km (5.2km-7.4km) and 11.2km (9.5km-12.8km), respectively. We were also able to capture the drop in mean transmission distance over the course of the outbreak. Our approach is applicable across diseases, robust to under-reporting and can inform interventions and surveillance.",,"['Salje, Henrik', 'Cummings, Derek A. T.', 'Lessler, Justin']",,,,
,PMC,Passive Immunotherapy: Assessment of Convalescent Serum Against Ebola Virus Makona Infection in Nonhuman Primates,http://dx.doi.org/10.1093/infdis/jiw333,PMC5050484,,,"Background. Convalescent serum and blood were used to treat patients during outbreaks of Zaire ebolavirus (ZEBOV) infection in 1976 and 1995, with inconclusive results. During the recent 2013–2016 West African epidemic, serum/plasma from survivors of ZEBOV infection was used to treat patients in the affected countries and several repatriated patients. The effectiveness of this strategy remains unknown. Methods. Nine rhesus monkeys were experimentally infected with ZEBOV-Makona. Beginning on day 3 after exposure (at the onset of viremia), 4 animals were treated with homologous ZEBOV-Makona convalescent macaque sera, 3 animals were treated in parallel with heterologous Sudan ebolavirus (SEBOV) convalescent macaque sera, and 2 animals served as positive controls and were not treated. Surviving animals received additional treatments on days 6 and 9. Results. Both untreated control animals died on postinfection day 9. All 4 ZEBOV-Makona–infected macaques treated with homologous ZEBOV-Makona convalescent sera died on days 8–9. One macaque treated with heterologous SEBOV convalescent sera survived, while the other animals treated with the heterologous SEBOV sera died on days 7 and 9. Conclusions. The findings suggest that convalescent sera alone is not sufficient for providing 100% protection against lethal ZEBOV infection when administered at the onset of viremia.",,"['Mire, Chad E.', 'Geisbert, Joan B.', 'Agans, Krystle N.', 'Thi, Emily P.', 'Lee, Amy C.H.', 'Fenton, Karla A.', 'Geisbert, Thomas W.']",,,,
,PMC,Alisporivir Has Limited Antiviral Effects Against Ebola Virus Strains Makona and Mayinga,http://dx.doi.org/10.1093/infdis/jiw241,PMC5050471,,,"Antiviral therapeutics with existing clinical safety profiles would be highly desirable in an outbreak situation, such as the 2013–2016 emergence of Ebola virus (EBOV) in West Africa. Although, the World Health Organization declared the end of the outbreak early 2016, sporadic cases of EBOV infection have since been reported. Alisporivir is the most clinically advanced broad-spectrum antiviral that functions by targeting a host protein, cyclophilin A (CypA). A modest antiviral effect of alisporivir against contemporary (Makona) but not historical (Mayinga) EBOV strains was observed in tissue culture. However, this effect was not comparable to observations for an alisporivir-susceptible virus, the flavivirus tick-borne encephalitis virus. Thus, EBOV does not depend on (CypA) for replication, in contrast to many other viruses pathogenic to humans.",,"['Chiramel, Abhilash I.', 'Banadyga, Logan', 'Dougherty, Jonathan D.', 'Falzarano, Darryl', 'Martellaro, Cynthia', 'Brees, Dominique', 'Taylor, R. Travis', 'Ebihara, Hideki', 'Best, Sonja M.']",,,,
,PMC,Broad and Temperature Independent Replication Potential of Filoviruses on Cells Derived From Old and New World Bat Species,http://dx.doi.org/10.1093/infdis/jiw199,PMC5050464,,,"Filoviruses are strongly associated with several species of bats as their natural reservoirs. In this study, we determined the replication potential of all filovirus species: Marburg marburgvirus, Taï Forest ebolavirus, Reston ebolavirus, Sudan ebolavirus, Zaire ebolavirus, and Bundibugyo ebolavirus. Filovirus replication was supported by all cell lines derived from 6 Old and New World bat species: the hammer-headed fruit bat, Buettikofer's epauletted fruit bat, the Egyptian fruit bat, the Jamaican fruit bat, the Mexican free-tailed bat and the big brown bat. In addition, we showed that Marburg virus Angola and Ebola virus Makona-WPGC07 efficiently replicated at 37°C, 37°–41°C, or 41°C, contrary to the hypothesis that temporal elevation in temperature due to flight affects filovirus replication in bats.",,"['Miller, Megan R.', 'McMinn, Rebekah J.', 'Misra, Vikram', 'Schountz, Tony', 'Müller, Marcel A.', 'Kurth, Andreas', 'Munster, Vincent J.']",,,,
,PMC,Comparison of the Aerosol Stability of 2 Strains of Zaire ebolavirus From the 1976 and 2013 Outbreaks,http://dx.doi.org/10.1093/infdis/jiw193,PMC5050463,,,"The largest outbreak of Ebola virus disease began in Guéckédou, Guinea, West Africa, in December 2013 and rapidly spread to major population centers in 3 West African countries. Early reports in some scientific and public media speculated that the virus had evolved to more effectively transmit between humans. One route of transmission postulated was aerosol transmission, although there was little epidemiological evidence to support this claim. This study investigates the viability of 2 Zaire ebolavirus strains within aerosols at 22°C and 80% relative humidity over time. The results presented here indicate that there is no difference in virus stability between the 2 strains and that viable virus can be recovered from an aerosol 180 minutes after it is generated.",,"['Fischer, Robert J.', 'Bushmaker, Trenton', 'Judson, Seth', 'Munster, Vincent J.']",,,,
,PMC,Crosstalk between autophagy and inflammatory signaling pathways: balancing host defence and homeostasis,http://dx.doi.org/10.1038/nri.2016.100,PMC5343289,,,"Autophagy has broad functions in immunity ranging from cell autonomous defense to coordination of complex multicellular responses. The successful resolution of infection and avoidance of autoimmunity necessitates efficient and timely communication between autophagy and pathways that sense the immune environment. In this article, progress in elucidating mechanisms of crosstalk between autophagy and inflammatory signaling cascades will be reviewed. The recent literature indicates that a variety of immune mediators induce or repress autophagy. It is also becoming increasing clear that immune signaling cascades are subject to regulation by autophagy, and that a return to homeostasis following a robust immune response is critically dependent on this pathway. Importantly, examples of non-canonical forms of autophagy in mediating immunity are pervasive. Improved mechanistic understanding of the autophagy machinery offers hope for treating infectious and inflammatory diseases.",,"Cadwell, Ken",,,,
,PMC,Assessing the efficacy of tabs on filtering facepiece respirator straps to increase proper doffing techniques while reducing contact transmission of pathogens,http://dx.doi.org/10.1080/15459624.2016.1179386,PMC5682596,,,"NIOSH-certified N95 filtering facepiece respirators (FFRs) are used in healthcare settings as a control measure to mitigate exposures to airborne infectious particles. When the outer surface of an FFR becomes contaminated, it presents a contact transmission risk to the wearer. The Centers for Disease Control and Prevention (CDC) guidance recommends that healthcare workers (HCWs) doff FFRs by grasping the straps at the back of the head to avoid contact with the potentially contaminated surface. Adherence to proper doffing technique is reportedly low due to numerous factors including difficulty in locating and grasping the straps. This study compares the impact of tabs placed on FFR straps to controls (without tabs) on proper doffing, ease of use and comfort, and reduction of transfer of contamination to the wearer. Utilizing a fluorescent agent as a tracer to track contamination from FFRs to hand and head areas of 20 human subjects demonstrated that there was no difference in tabbed FFR straps and controls with respect to promoting proper doffing (p = 0.48), but did make doffing easier (p = 0.04) as indicated by 7 of 8 subjects that used the tabs. Seven of the 20 subjects felt that FFRs with tabs were easier to remove, while only 2 of 20 indicated that FFRs without tabs were easier to remove. Discomfort was not a factor for either FFR strap type. When removing an FFR with contaminated hands, the use of the tabs significantly reduced the amount of tracer transfer compared to straps without tabs (p = 0.012). FFRs with tabs on the straps are associated with ease of doffing and significantly less transfer of the fluorescent tracer.",,"['Strauch, Amanda L.', 'Brady, Tyler M.', 'Niezgoda, George', 'Almaguer, Claudia M.', 'Shaffer, Ronald E.', 'Fisher, Edward M.']",,,,
,PMC,Mortality Due to Porcine Reproductive and Respiratory Syndrome Virus in Immunocompromised Göttingen Minipigs (Sus scrofa domestica),,PMC5073064,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) infection was diagnosed in 6 Göttingen minipigs (Sus scrofa domestica) with severe interstitial pneumonia. The virus was defined as a North American (NA) subtype virus, which is common in the commercial pig population and might be derived from a widely used attenuated live-virus vaccine in Europe. The ORF5 sequence of the isolated PRRSV was 98% identical to the vaccine virus. The affected pigs were part of a lung transplantation model and received tacrolimus and steroids as well as irradiation or CD8 antibody for immunosuppression. The likely source of the infection was pigs that were shedding the identified PRRSV, which were housed in a separate room of the same building. This case report provides evidence that a virus closely related to an attenuated live vaccine might cause severe pneumonia and death in PRRSV-seronegative pigs receiving immunosuppressive treatment. We recommend strict barrier housing for immunocompromised pigs.",,"['Pils, Marina C', 'Dreckmann, Karla', 'Jansson, Katharina', 'Glage, Silke', 'Held, Nadine', 'Sommer, Wiebke', 'Länger, Florian', 'Avsar, Murat', 'Warnecke, Gregor', 'Bleich, André']",,,,
,PMC,Effects of Colored Enrichment Devices on Circadian Metabolism and Physiology in Male Sprague–Dawley Rats,,PMC5073063,,,"Environmental enrichment (EE) gives laboratory animals opportunities to engage in species-specific behaviors. However, the effects of EE devices on normal physiology and scientific outcomes must be evaluated. We hypothesized that the spectral transmittance (color) of light to which rats are exposed when inside colored enrichment devices (CED) affects the circadian rhythms of various plasma markers. Pair-housed male Crl:SD rats were maintained in ventilated racks under a 12:12-h light:dark environment (265.0 lx; lights on, 0600); room lighting intensity and schedule remained constant throughout the study. Treatment groups of 6 subjects were exposed for 25 d to a colored enrichment tunnel: amber, red, clear, or opaque. We measured the proportion of time rats spent inside their CED. Blood was collected at 0400, 0800, 1200, 1600, 2000, and 2400 and analyzed for plasma melatonin, total fatty acids, and corticosterone. Rats spent more time in amber, red, and opaque CED than in clear tunnels. All tubes were used significantly less after blood draws had started, except for the clear tunnel, which showed no change in use from before blood sampling began. Normal peak nighttime melatonin concentrations showed significant disruption in the opaque CED group. Food and water intakes and body weight change in rats with red-tinted CED and total fatty acid concentrations in the opaque CED group differed from those in other groups. These results demonstrate that the color of CED altered normal circadian rhythms of plasma measures of metabolism and physiology in rats and therefore might influence the outcomes of scientific investigations.",,"['Wren-Dail, Melissa A', 'Dauchy, Robert T', 'Ooms, Tara G', 'Baker, Kate C', 'Blask, David E', 'Hill, Steven M', 'Dupepe, Lynell M', 'Bohm, Rudolf P']",,,,
,PMC,DPP4 Inhibition: Insights From the Bench and Recent Clinical Studies,http://dx.doi.org/10.1097/MOL.0000000000000340,PMC5147592,,,"PURPOSE OF REVIEW: Atherosclerosis is the leading cause of death globally. The pathophysiology of atherosclerosis is not fully understood. Recent studies suggest dipeptidyl peptidase-4 (DPP4), a regulator of inflammation and metabolism, may be involved in the development of atherosclerotic diseases. Recent advances in the understanding of DPP4 function in atherosclerosis will be discussed in this review. RECENT FINDINGS: Multiple pre-clinical and clinical studies suggest DPP4/GLP-1 axis is involved in the development of atherosclerotic disease. However, several recent trials assessing the cardiovascular effects of DPP4 inhibition indicate enzymatic inhibition of DPP4 lacks beneficial effects on cardiovascular disease. SUMMARY: Catalytic inhibition of DPP4 with DPP4i alters pathways that could favor cardioprotection. GLP-1R-independent aspects of DPP4 function may contribute to the overall neutral effects on cardiovascular outcome seen in the outcome trials.",,"['Zhong, Jixin', 'Kankanala, Saumya', 'Rajagopalan, Sanjay']",,,,
,PMC,Recurring Bilateral Rash Concomitant With Upper Respiratory Tract Infection in a Healthy Adult Male,,PMC6373713,,,An unusual presentation highlighted the unique health maintenance challenges of reservist patients and the importance of a thorough history for proper diagnosis.,,"Schwartz, Michael D.",,,,
,PMC,Malware and Disease: Lessons from Cyber Intelligence for Public Health Surveillance,http://dx.doi.org/10.1089/hs.2015.0077,PMC5041502,,,"Malicious software and infectious diseases are similar is several respects, as are the functional requirements for surveillance and intelligence to defend against these threats. Given these similarities, this article compares and contrasts the actors, relationships, and norms at work in cyber intelligence and disease surveillance. Historical analysis reveals that civilian cyber defense is more decentralized, private, and voluntary than public health in the United States. Most of these differences are due to political choices rather than technical necessities. In particular, political resistance to government institutions has shaped cyber intelligence over the past 30 years, which is a troubling sign for attempts to improve disease surveillance through local, state, and federal health departments. Information sharing about malware is also limited, despite information technology being integral to cyberspace. Such limits suggest that automation through electronic health records will not automatically improve public health surveillance. Still, certain aspects of information sharing and analysis for cyber defense are worth emulating or, at the very least, learning from to help detect and manage health threats.",,"Smith, Frank L.",,,,
,PMC,Using Patient-Specific Induced Pluripotent Stem Cells and Wild-Type Mice to Develop a Gene Augmentation-Based Strategy to Treat CLN3-Associated Retinal Degeneration,http://dx.doi.org/10.1089/hum.2016.049,PMC5035933,,,"Juvenile neuronal ceroid lipofuscinosis (JNCL) is a childhood neurodegenerative disease with early-onset, severe central vision loss. Affected children develop seizures and CNS degeneration accompanied by severe motor and cognitive deficits. There is no cure for JNCL, and patients usually die during the second or third decade of life. In this study, independent lines of induced pluripotent stem cells (iPSCs) were generated from two patients with molecularly confirmed mutations in CLN3, the gene mutated in JNCL. Clinical-grade adeno-associated adenovirus serotype 2 (AAV2) carrying the full-length coding sequence of human CLN3 was generated in a U.S. Food and Drug Administration-registered cGMP facility. AAV2-CLN3 was efficacious in restoring full-length CLN3 transcript and protein in patient-specific fibroblasts and iPSC-derived retinal neurons. When injected into the subretinal space of wild-type mice, purified AAV2-CLN3 did not show any evidence of retinal toxicity. This study provides proof-of-principle for initiation of a clinical trial using AAV-mediated gene augmentation for the treatment of children with CLN3-associated retinal degeneration.",,"['Wiley, Luke A.', 'Burnight, Erin R.', 'Drack, Arlene V.', 'Banach, Bailey B.', 'Ochoa, Dalyz', 'Cranston, Cathryn M.', 'Madumba, Robert A.', 'East, Jade S.', 'Mullins, Robert F.', 'Stone, Edwin M.', 'Tucker, Budd A.']",,,,
,PMC,The utility of margin-reflex distance in determining the type of surgical intervention for congenital blepharoptosis,http://dx.doi.org/10.4103/0301-4738.195016,PMC5168917,27905338,CC BY-NC-SA,"AIMS: To evaluate the utility of margin-reflex distance (MRD) as an alternative to levator function (LF) in choosing the appropriate surgical procedure for congenital blepharoptosis. SETTINGS AND DESIGN: This was a retrospective, observational study. SUBJECTS AND METHODS: Records of patients with simple (dystrophic) congenital ptosis who were operated and followed for ≥6 months postoperatively and whose outcomes were deemed as successful were evaluated in the study. Success was defined as a MRD at the last postoperative visit of ≥3 mm. In all cases, levator resection was performed when LF was >4 mm and frontalis suspension when LF was ≤4 mm. STATISTICAL ANALYSIS USED: For statistical evaluations, LF was accepted as the gold standard parameter for deciding on the surgical intervention, and the optimum cutoff point for initial MRD was determined as the point at which sensitivity and specificity was highest at the receiving operating curve for the selection of surgical procedure. RESULTS: Of one hundred and three eyes of ninety patients (44 female/46 male), levator resection was used in 44.7% and frontalis suspension in 55.3%. When the optimum cutoff point for MRD was determined as 0.5 mm, the sensitivity was 71%, specificity was 86%, and the area under the curve that represented the discriminative power of this parameter was found to be 0.826. CONCLUSION: The MRD at the cutoff point of 0.5 mm may be used as an alternative to LF to determine the type of surgical intervention in patients with congenital blepharoptosis whose LF cannot be reliably obtained in clinical evaluations.",2016 Oct,"['Ural, Ozlem', 'Mocan, Mehmet Cem', 'Dolgun, Anıl', 'Erdener, Ugur']",Indian J Ophthalmol,,,
,PMC,Consensus Recommendation for India and Bangladesh for the Use of Pneumococcal Vaccine in Mass Gatherings with Special Reference to Hajj Pilgrims,http://dx.doi.org/10.4103/0974-777X.193749,PMC5126751,27942192,CC BY-NC-SA,"Respiratory tract infections are prevalent among Hajj pilgrims with pneumonia being a leading cause of hospitalization. Streptococcus pneumoniae is a common pathogen isolated from patients with pneumonia and respiratory tract infections during Hajj. There is a significant burden of pneumococcal disease in India, which can be prevented. Guidelines for preventive measures and adult immunization have been published in India, but the implementation of the guidelines is low. Data from Bangladesh are available about significant mortality due to respiratory infections; however, literature regarding guidelines for adult immunization is limited. There is a need for extensive awareness programs across India and Bangladesh. Hence, there was a general consensus about the necessity for a rapid and urgent implementation of measures to prevent respiratory infections in pilgrims traveling to Hajj. About ten countries have developed recommendations for pneumococcal vaccination in Hajj pilgrims: France, the USA, Kuwait, Qatar, Bahrain, the UAE (Dubai Health Authority), Singapore, Malaysia, Egypt, and Indonesia. At any given point whether it is Hajj or Umrah, more than a million people are present in the holy places of Mecca and Madina. Therefore, the preventive measures taken for Hajj apply for Umrah as well. This document puts forward the consensus recommendations by a group of twenty doctors following a closed-door discussion based on the scientific evidence available for India and Bangladesh regarding the prevention of respiratory tract infections in Hajj pilgrims.",2016 Oct-Dec,"['Mathai, Dilip', 'Shamsuzzaman, Abul Khair Mohammad', 'Feroz, Ahrar Ahmed', 'Virani, Amin R', 'Hasan, Ashfaq', 'Ravi Kumar, KL', 'Ansari, Khalid', 'Forhad Hossain, Khandaker ATM', 'Marda, Mahesh', 'Wahab Zubair, MA', 'Ali, Mohammed Mukarram', 'Ashraf, N', 'Basha, Riyaz', 'Mirza, Shaeq', 'Ahmed, Shafeeq', 'Akhtar, Shamim', 'Ashraf, Syed Mustafa', 'Haque, Zahirul']",J Glob Infect Dis,,,
,PMC,Successful treatment of suspected organizing pneumonia in a patient with Middle East respiratory syndrome coronavirus infection: a case report,http://dx.doi.org/10.21037/jtd.2016.09.26,PMC5107491,,,"A 54-year-old man with Middle East respiratory syndrome coronavirus (MERS-CoV) infection was transferred to our hospital. We initiated anti-viral drugs and supportive care. The patient’s fever and chills disappeared 3 days after admission and the results of serial follow-up reverse transcription-polymerase chain reaction testing for MERS-CoV was negative soon thereafter. He was discharged from the hospital 14 days after admission with no symptoms; however, he presented with a fever 7 days after discharge and was re-hospitalized. Chest radiographs showed newly developed consolidative opacity. His fever persisted for 3 days after commencing empirical antibiotics. Subsequent contrast-enhanced computed tomography (CT) of the chest showed focal patchy airspace consolidation and ground-glass opacities (GGOs) in a subpleural lesion of the right lower and left upper lobes, which was indicative of organizing pneumonia. We initiated empirical corticosteroid treatment for this illness, and his fever markedly subsided 1 day later. A chest radiograph showed improvement in the lung lesions, and he was discharged from the hospital 10 days after re-admission. The corticosteroid dose was gradually tapered over 2 months at the outpatient clinic, and a follow-up CT scan showed complete resolution of the consolidation and GGOs.",,"['Kim, Insu', 'Lee, Jeong Eun', 'Kim, Kye-Hyung', 'Lee, Shinwon', 'Lee, Kwangha', 'Mok, Jeong Ha']",,,,
,PMC,Historical Data Analysis of Hospital Discharges Related to the Amerithrax Attack in Florida,,PMC5075231,,,"Interrupted time-series analysis (ITSA) can be used to identify, quantify, and evaluate the magnitude and direction of an event on the basis of time-series data. This study evaluates the impact of the bioterrorist anthrax attacks (“Amerithrax”) on hospital inpatient discharges in the metropolitan statistical area of Palm Beach, Broward, and Miami-Dade counties in the fourth quarter of 2001. Three statistical methods—standardized incidence ratio (SIR), segmented regression, and an autoregressive integrated moving average (ARIMA)—were used to determine whether Amerithrax influenced inpatient utilization. The SIR found a non–statistically significant 2 percent decrease in hospital discharges. Although the segmented regression test found a slight increase in the discharge rate during the fourth quarter, it was also not statistically significant; therefore, it could not be attributed to Amerithrax. Segmented regression diagnostics preparing for ARIMA indicated that the quarterly data time frame was not serially correlated and violated one of the assumptions for the use of the ARIMA method and therefore could not properly evaluate the impact on the time-series data. Lack of data granularity of the time frames hindered the successful evaluation of the impact by the three analytic methods. This study demonstrates that the granularity of the data points is as important as the number of data points in a time series. ITSA is important for the ability to evaluate the impact that any hazard may have on inpatient utilization. Knowledge of hospital utilization patterns during disasters offer healthcare and civic professionals valuable information to plan, respond, mitigate, and evaluate any outcomes stemming from biothreats.",,"['Burke, Lauralyn K.', 'Brown, C. Perry', 'Johnson, Tammie M.']",,,,
,PMC,Innovating for future health,http://dx.doi.org/10.11622/smedj.2016164,PMC5075952,,,,,"Chuan, Tan Chorh",,,,
,PMC,Intragraft Antiviral-specific Gene Expression as a Distinctive Transcriptional Signature for Studies in Polyomavirus Associated Nephropathy,http://dx.doi.org/10.1097/TP.0000000000001214,PMC5235336,,,"BACKGROUND: Polyomavirus nephropathy (PVAN) is a common cause of kidney allograft dysfunction and loss. To identify PVAN-specific gene expression and underlying molecular mechanisms we analyzed kidney biopsies with and without PVAN. METHODS: The study included 168 posttransplant renal allograft biopsies (T cell mediated rejection=26, PVAN=10, normal functioning graft (STA) =73, and interstitial fibrosis/tubular atrophy (IF/TA) =59) from 168 unique kidney allograft recipients. We performed gene expression assays and bioinformatics analysis to identify a set of PVAN-specific genes. Validity and relevance of a subset of these genes are validated by QPCR and IHC. RESULTS: Unsupervised hierarchical clustering analysis of all the biopsies revealed high similarity between PVAN and TCMR gene expression. Increased statistical stringency identified 158 and 252 unique PVAN and TCMR injury-specific gene transcripts respectively. While TCMR-specific genes were overwhelmingly involved in immune response costimulation and TCR signaling, PVAN-specific genes were mainly related to DNA replication process, RNA polymerase assembly and pathogen recognition receptors. A principal component analysis using these genes further confirmed the most optimal separation between the 3 different clinical phenotypes. Validation of 4 PVAN-specific genes (RPS15, CFD, LTF, and NOSIP) by QPCR and confirmation by immunohistochemistry of 2 PVAN-specific proteins with anti-viral function (LTF and IFITM1) was done. CONCLUSIONS: In conclusion, even though PVAN and TCMR kidney allografts share great similarities on gene perturbation, PVAN-specific genes were identified with well-known anti-viral properties that provide tools for discerning PVAN and AR as well as attractive targets for rational drug design.",,"['Sigdel, Tara K.', 'Bestard, Oriol', 'Salomonis, Nathan', 'Hsieh, Szu-Chuan', 'Torras, Joan', 'Naesens, Maarten', 'Tran, Tim Q.', 'Roedder, Silke', 'Sarwal, Minnie M.']",,,,
,PMC,Simulation Study on Effects of Order and Step Size of Runge-Kutta Methods that Solve Contagious Disease and Tumor Models,http://dx.doi.org/10.4172/jcsb.1000234,PMC5316286,,,"Biological processes such as contagious disease spread patterns and tumor growth dynamics are modelled using a set of coupled differential equations. Experimental data is usually used to calibrate models so they can be used to make future predictions. In this study, numerical methods were implemented to approximate solutions to mathematical models that were not solvable analytically, such as a SARS model. More complex models such as a tumor growth model involve high-dimensional parameter spaces; efficient numerical simulation techniques were used to search for optimal or close-to-optimal parameter values in the equations. Runge-Kutta methods are a group of explicit and implicit numerical methods that effectively solve the ordinary differential equations in these models. Effects of the order and the step size of Runge-Kutta methods were studied in order to maximize the search accuracy and efficiency in parameter spaces of the models. Numerical simulation results showed that an order of four gave the best balance between truncation errors and the simulation speed for SIR, SARS, and tumormodels studied in the project. The optimal step size for differential equation solvers was found to be model-dependent.",,"['Z, Wang', 'Q, Wang', 'DJ, Klinke']",,,,
,PMC,Mouse Hepatitis Virus Infection Induces a Toll-Like Receptor 2-Dependent Activation of Inflammatory Functions in Liver Sinusoidal Endothelial Cells during Acute Hepatitis,http://dx.doi.org/10.1128/JVI.01069-16,PMC5044860,,,"Under physiological conditions, the liver sinusoidal endothelial cells (LSECs) mediate hepatic immune tolerance toward self or foreign antigens through constitutive expression of anti-inflammatory mediators. However, upon viral infection or Toll-like receptor 2 (TLR2) activation, LSECs can achieve proinflammatory functions, but their role in hepatic inflammation during acute viral hepatitis is unknown. Using the highly virulent mouse hepatitis virus type 3 (MHV3) and the attenuated variants 51.6-MHV3 and YAC-MHV3, exhibiting lower tropism for LSECs, we investigated in vivo and in vitro the consequence of LSEC infection on their proinflammatory profiles and the aggravation of acute hepatitis process. In vivo infection with virulent MHV3, in comparison to attenuated strains, resulted in fulminant hepatitis associated with higher hepatic viral load, tissue necrosis, and levels of inflammatory mediators and earlier recruitment of inflammatory cells. Such hepatic inflammatory disorders correlated with disturbed production of interleukin-10 (IL-10) and vascular factors by LSECs. We next showed in vitro that infection of LSECs by the virulent MHV3 strain altered their production of anti-inflammatory cytokines and promoted higher release of proinflammatory and procoagulant factors and earlier cell damage than infection by attenuated strains. This higher replication and proinflammatory activation in LSECs by the virulent MHV3 strain was associated with a specific activation of TLR2 signaling by the virus. We provide evidence that TLR2 activation of LSCEs by MHV3 is an aggravating factor of hepatic inflammation and correlates with the severity of hepatitis. Taken together, these results indicate that preservation of the immunotolerant properties of LSECs during acute viral hepatitis is imperative in order to limit hepatic inflammation and damage. IMPORTANCE Viral hepatitis B and C infections are serious health problems affecting over 350 million and 170 million people worldwide, respectively. It has been suggested that a balance between protection and liver damage mediated by the host's immune response during the acute phase of infection would be determinant in hepatitis outcome. Thus, it appears crucial to identify the factors that predispose in exacerbating liver inflammation to limit hepatocyte injury. Liver sinusoidal endothelial cells (LSECs) can express both anti- and proinflammatory functions, but their role in acute viral hepatitis has never been investigated. Using mouse hepatitis virus (MHV) infections as animal models of viral hepatitis, we report for the first time that in vitro and in vivo infection of LSECs by the pathogenic MHV3 serotype leads to a reversion of their intrinsic anti-inflammatory phenotype toward a proinflammatory profile as well to as disorders in vascular factors, correlating with the severity of hepatitis. These results highlight a new virus-promoted mechanism of exacerbation of liver inflammatory response during acute hepatitis.",,"['Bleau, Christian', 'Filliol, Aveline', 'Samson, Michel', 'Lamontagne, Lucie']",,,,
,PMC,In Vivo Conditions Enable IFNAR-Independent Type I Interferon Production by Peritoneal CD11b(+) Cells upon Thogoto Virus Infection,http://dx.doi.org/10.1128/JVI.00744-16,PMC5044850,,,"Type I interferons (IFNs) crucially contribute to host survival upon viral infections. Robust expression of type I IFNs (IFN-α/β) and induction of an antiviral state critically depend on amplification of the IFN signal via the type I IFN receptor (IFNAR). A small amount of type I IFN produced early upon virus infection binds the IFNAR and activates a self-enhancing positive feedback loop, resulting in induction of large, protective amounts of IFN-α. Unexpectedly, we found robust, systemic IFN-α expression upon infection of IFNAR knockout mice with the orthomyxovirus Thogoto virus (THOV). The IFNAR-independent IFN-α production required in vivo conditions and was not achieved during in vitro infection. Using replication-incompetent THOV-derived virus-like particles, we demonstrate that IFNAR-independent type I IFN induction depends on viral polymerase activity but is largely independent of viral replication. To discover the cell type responsible for this effect, we used type I IFN reporter mice and identified CD11b(+) F4/80(+) myeloid cells within the peritoneal cavity of infected animals as the main source of IFNAR-independent type I IFN, corresponding to the particular tropism of THOV for this cell type. IMPORTANCE Type I IFNs are crucial for the survival of a host upon most viral infections, and, moreover, they shape subsequent adaptive immune responses. Production of protective amounts of type I IFN critically depends on the positive feedback amplification via the IFNAR. Unexpectedly, we observed robust IFNAR-independent type I IFN expression upon THOV infection and unraveled molecular mechanisms and determined the tissue and cell type involved. Our data indicate that the host can effectively use alternative pathways to induce type I IFN responses if the classical feedback amplification is not available. Understanding how type I IFN can be produced in large amounts independently of IFNAR-dependent enhancement will identify mechanisms which might contribute to novel therapeutic strategies to fight viral pathogens.",,"['Kochs, Georg', 'Anzaghe, Martina', 'Kronhart, Stefanie', 'Wagner, Valentina', 'Gogesch, Patricia', 'Scheu, Stefanie', 'Lienenklaus, Stefan', 'Waibler, Zoe']",,,,
,PMC,Inhibition of Human Metapneumovirus Binding to Heparan Sulfate Blocks Infection in Human Lung Cells and Airway Tissues,http://dx.doi.org/10.1128/JVI.01362-16,PMC5044844,,,"Human metapneumovirus (HMPV), a recently discovered paramyxovirus, infects nearly 100% of the world population and causes severe respiratory disease in infants, the elderly, and immunocompromised patients. We previously showed that HMPV binds heparan sulfate proteoglycans (HSPGs) and that HMPV binding requires only the viral fusion (F) protein. To characterize the features of this interaction critical for HMPV binding and the role of this interaction in infection in relevant models, we utilized sulfated polysaccharides, heparan sulfate mimetics, and occluding compounds. Iota-carrageenan demonstrated potent anti-HMPV activity by inhibiting binding to lung cells mediated by the F protein. Furthermore, analysis of a minilibrary of variably sulfated derivatives of Escherichia coli K5 polysaccharide mimicking the HS structure revealed that the highly O-sulfated K5 polysaccharides inhibited HMPV infection, identifying a potential feature of HS critical for HMPV binding. The peptide dendrimer SB105-A10, which binds HS, reduced binding and infection in an F-dependent manner, suggesting that occlusion of HS at the target cell surface is sufficient to prevent infection. HMPV infection was also inhibited by these compounds during apical infection of polarized airway tissues, suggesting that these interactions take place during HMPV infection in a physiologically relevant model. These results reveal key features of the interaction between HMPV and HS, supporting the hypothesis that apical HS in the airway serves as a binding factor during infection, and HS modulating compounds may serve as a platform for potential antiviral development. IMPORTANCE Human metapneumovirus (HMPV) is a paramyxovirus that causes respiratory disease worldwide. It has been previously shown that HMPV requires binding to heparan sulfate on the surfaces of target cells for attachment and infection. In this study, we characterize the key features of this binding interaction using heparan sulfate mimetics, identify an important sulfate modification, and demonstrate that these interactions occur at the apical surface of polarized airway tissues. These findings provide insights into the initial binding step of HMPV infection that has potential for antiviral development.",,"['Klimyte, Edita M.', 'Smith, Stacy E.', 'Oreste, Pasqua', 'Lembo, David', 'Dutch, Rebecca Ellis']",,,,
,PMC,Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 Is an Important Surface Attachment Factor That Facilitates Entry of Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.01133-16,PMC5044831,,,"The spike proteins of coronaviruses are capable of binding to a wide range of cellular targets, which contributes to the broad species tropism of coronaviruses. Previous reports have demonstrated that Middle East respiratory syndrome coronavirus (MERS-CoV) predominantly utilizes dipeptidyl peptidase 4 (DPP4) for cell entry. However, additional cellular binding targets of the MERS-CoV spike protein that may augment MERS-CoV infection have not been further explored. In the current study, using the virus overlay protein binding assay (VOPBA), we identified carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface binding target of MERS-CoV. CEACAM5 coimmunoprecipitated with the spike protein of MERS-CoV in both overexpressed and endogenous settings. Disrupting the interaction between CEACAM5 and MERS-CoV spike with anti-CEACAM5 antibody, recombinant CEACAM5 protein, or small interfering RNA (siRNA) knockdown of CEACAM5 significantly inhibited the entry of MERS-CoV. Recombinant expression of CEACAM5 did not render nonpermissive baby hamster kidney (BHK21) cells susceptible to MERS-CoV infection. Instead, CEACAM5 overexpression significantly enhanced the attachment of MERS-CoV to the BHK21 cells. More importantly, the entry of MERS-CoV was increased when CEACAM5 was overexpressed in permissive cells, which suggested that CEACAM5 could facilitate MERS-CoV entry in conjunction with DPP4 despite not being able to support MERS-CoV entry independently. Taken together, the results of our study identified CEACAM5 as a novel cell surface binding target of MERS-CoV that facilitates MERS-CoV infection by augmenting the attachment of the virus to the host cell surface. IMPORTANCE Infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with the highest mortality rate among all known human-pathogenic coronaviruses. Currently, there are no approved vaccines or therapeutics against MERS-CoV infection. The identification of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface binding target of MERS-CoV advanced our knowledge on the cell binding biology of MERS-CoV. Importantly, CEACAM5 could potentiate the entry of MERS-CoV by functioning as an attachment factor. In this regard, CEACAM5 could serve as a novel target, in addition to dipeptidyl peptidase-4 (DPP4), in the development of antiviral strategies for MERS-CoV.",,"['Chan, Che-Man', 'Chu, Hin', 'Wang, Yixin', 'Wong, Bosco Ho-Yin', 'Zhao, Xiaoyu', 'Zhou, Jie', 'Yang, Dong', 'Leung, Sze Pui', 'Chan, Jasper Fuk-Woo', 'Yeung, Man-Lung', 'Yan, Jinghua', 'Lu, Guangwen', 'Gao, George Fu', 'Yuen, Kwok-Yung']",,,,
,PMC,Protective Effects of Glutamine Antagonist 6-Diazo-5-Oxo-l-Norleucine in Mice with Alphavirus Encephalomyelitis,http://dx.doi.org/10.1128/JVI.01045-16,PMC5044826,,,"Inflammation is a necessary part of the response to infection but can also cause neuronal injury in both infectious and autoimmune diseases of the central nervous system (CNS). A neurovirulent strain of Sindbis virus (NSV) causes fatal paralysis in adult C57BL/6 mice during clearance of infectious virus from the CNS, and the virus-specific immune response is implicated as a mediator of neuronal damage. Previous studies have shown that survival is improved in T-cell-deficient mice and in mice with pharmacological inhibition of the inflammatory response and glutamate excitotoxicity. Because glutamine metabolism is important in the CNS for the generation of glutamate and in the immune system for lymphocyte proliferation, we tested the effect of the glutamine antagonist DON (6-diazo-5-oxo-l-norleucine) on the outcome of NSV infection in mice. DON treatment for 7 days from the time of infection delayed the onset of paralysis and death. Protection was associated with reduced lymphocyte proliferation in the draining cervical lymph nodes, decreased leukocyte infiltration into the CNS, lower levels of inflammatory cytokines, and delayed viral clearance. In vitro studies showed that DON inhibited stimulus-induced proliferation of lymphocytes. When in vivo treatment with DON was stopped, paralytic disease developed along with the inflammatory response and viral clearance. These studies show that fatal NSV-induced encephalomyelitis is immune mediated and that antagonists of glutamine metabolism can modulate the immune response and protect against virus-induced neuroinflammatory disease. IMPORTANCE Encephalomyelitis due to infection with mosquito-borne alphaviruses is an important cause of death and of long-term neurological disability in those who survive infection. This study demonstrates the role of the virus-induced immune response in the generation of neurological disease. DON, a glutamine antagonist, inhibited the proliferation of lymphocytes in response to infection, prevented the development of brain inflammation, and protected mice from paralysis and death during treatment. However, because DON inhibited the immune response to infection, clearance of the virus from the brain was also prevented. When treatment was stopped, the immune response was generated, brain inflammation occurred, virus was cleared, and mice developed paralysis and died. Therefore, more definitive treatment for alphaviral encephalomyelitis should inhibit virus replication as well as neuroinflammatory damage.",,"['Manivannan, Sivabalan', 'Baxter, Victoria K.', 'Schultz, Kimberly L. W.', 'Slusher, Barbara S.', 'Griffin, Diane E.']",,,,
,PMC,RIG-I-Mediated STING Upregulation Restricts Herpes Simplex Virus 1 Infection,http://dx.doi.org/10.1128/JVI.00748-16,PMC5044816,,,"STING has emerged in recent years as a key player in orchestrating innate immune responses to cytosolic DNA and RNA derived from pathogens. However, the regulation of STING still remains poorly defined. In the present study, we investigated the mechanism of the regulation of STING expression in relation to the RIG-I pathway. Our data show that signaling through RIG-I induces STING expression at both the transcriptional and protein levels in various cell types. STING induction by the RIG-I agonist 5′triphosphorylated RNA (5′pppRNA) was recognized to be a delayed event resulting from an autocrine/paracrine mechanism. Indeed, cotreatment with tumor necrosis factor alpha and type I/II interferon was found to have a synergistic effect on the regulation of STING expression and could be potently decreased by impairing NF-κB and/or STAT1/2 signaling. STING induction significantly contributed to sustainment of the immune signaling cascade following 5′pppRNA treatment. Physiologically, this cross talk between the RNA- and DNA-sensing pathways allowed 5′pppRNA to efficiently block infection by herpes simplex virus 1 (HSV-1) both in vitro and in vivo in a STING-dependent fashion. These observations demonstrate that STING induction by RIG-I signaling through the NF-κB and STAT1/2 cascades is essential for RIG-I agonist-mediated HSV-1 restriction. IMPORTANCE The innate immune system represents the first line of defense against invading pathogens. The dysregulation of this system can result in failure to combat pathogens, inflammation, and autoimmune diseases. Thus, precise regulation at each level of the innate immune system is crucial. Recently, a number of studies have established STING to be a central molecule in the innate immune response to cytosolic DNA and RNA derived from pathogens. Here, we describe the regulation of STING via RIG-I-mediated innate immune sensing. We found that STING is synergistically induced via proinflammatory and antiviral cytokine cascades. In addition, we show that in vivo protection against herpes simplex virus 1 (HSV-1) by a RIG-I agonist required STING. Our study provides new insights into the cross talk between DNA and RNA pathogen-sensing systems via the control of STING.",,"['Liu, Yiliu', 'Goulet, Marie-Line', 'Sze, Alexandre', 'Hadj, Samar Bel', 'Belgnaoui, Sidi Mehdi', 'Lababidi, Rassin R.', 'Zheng, Chunfu', 'Fritz, Jörg Hermann', 'Olagnier, David', 'Lin, Rongtuan']",,,,
,PMC,Astrocytes: Integrative Regulators of Neuroinflammation in Stroke and Other Neurological Diseases,http://dx.doi.org/10.1007/s13311-016-0477-8,PMC5081110,,,"Astrocytes regulate neuroinflammatory responses after stroke and in other neurological diseases. Although not all astrocytic responses reduce inflammation, their predominant function is to protect the brain by driving the system back to homeostasis after injury. They receive multidimensional signals within the central nervous system and between the brain and the systemic circulation. Processing this information allows astrocytes to regulate synapse formation and maintenance, cerebral blood flow, and blood–brain barrier integrity. Similarly, in response to stroke and other central nervous system disorders, astrocytes detect and integrate signals of neuronal damage and inflammation to regulate the neuroinflammatory response. Two direct regulatory mechanisms in the astrocyte arsenal are the ability to form both physical and molecular barriers that seal the injury site and localize the neuroinflammatory response. Astrocytes also indirectly regulate the inflammatory response by affecting neuronal health during the acute injury and axonal regrowth. This ability to regulate the location and degree of neuroinflammation after injury, combined with the long time course of neuroinflammation, makes astrocytic signaling pathways promising targets for therapies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13311-016-0477-8) contains supplementary material, which is available to authorized users.",,"['Cekanaviciute, Egle', 'Buckwalter, Marion S.']",,,,
,PMC,Development of a multiplex RT-PCR for simultaneous diagnosis of human metapneumovirus (HMPV) and human respiratory syncytial virus (HRSV) from clinical specimens,http://dx.doi.org/10.1007/s13337-016-0348-2,PMC5142592,,,"Human metapneumovirus (HMPV) and human respiratory syncytial virus (HRSV) are ubiquitous respiratory viral pathogens. They belong to the family Paramyxoviridae (subfamily Pneumovirinae) and is responsible for acute respiratory tract infections in children, elderly and immunocompromised patients. We designed and tested a multiplex reverse transcriptase polymerase chain reaction (mRT-PCR) as a cost-effective alternative to real-time PCR and cell culture based detection for HMPV and HRSV. The newly developed PCR was used to screen nasal/throat swab samples from 356 patients with suspected acute respiratory infection attending the Government Medical College, Thiruvananthapuram, Kerala, India. The method was compared with a commercially available kit employing real time PCR, for its sensitivity and specificity. 53 (14.9 %) samples were positive for at least one tested pathogen by mRT-PCR. All except one among the positive samples showed similar pathogen profile when tested using real time PCR. 8 (15.1 %) among these 53 were positive for HRSVA, 33 (62.3 %) positive for HRSVB and 12 (22.6 %) were positive for HMPV. 17 (32.7 %) samples showed co-infections in them. Sensitivity and specificity of the mRT-PCR was comparable to that of the commercial kit. Our findings indicate that this newly developed mRT-PCR can be used as a cost-effective alternative for laboratory diagnosis of HMPV/HRSV infection and will significantly reduce diagnostic costs for these viruses in clinical settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13337-016-0348-2) contains supplementary material, which is available to authorized users.",,"['Dayakar, Seetha', 'Pillai, Heera R.', 'Thulasi, Vineetha P.', 'Nair, Radhakrishnan R.']",,,,
,PMC,Efficacy and Immunogenicity of Unmodified and Pseudouridine-Modified mRNA Delivered Systemically with Lipid Nanoparticles in Vivo,http://dx.doi.org/10.1016/j.biomaterials.2016.09.006,PMC5267554,,,"mRNA has broad potential for treating diseases requiring protein expression. However, mRNA can also induce an immune response with associated toxicity. Replacement of uridine bases with pseudouridine has been postulated to modulate both mRNA immunogenicity and potency. Here, we explore the immune response and activity of lipid nanoparticle-formulated unmodified and pseudouridine-modified mRNAs administered systemically in vivo. Pseudouridine modification to mRNA had no significant effect on lipid nanoparticle physical properties, protein expression in vivo, or mRNA immunogenicity compared to unmodified mRNA when delivered systemically with liver-targeting lipid nanoparticles, but reduced in vitro transfection levels. Indicators of a transient, extracellular innate immune response to mRNA were observed, including neutrophilia, myeloid cell activation, and up-regulation of four serum cytokines. This study provides insight into the immune responses to mRNA lipid nanoparticles, and suggests that pseudouridine modifications may be unnecessary for therapeutic application of mRNA in the liver.",,"['Kauffman, Kevin J.', 'Mir, Faryal F.', 'Jhunjhunwala, Siddharth', 'Kaczmarek, James C.', 'Hurtado, Juan E.', 'Yang, Jung H.', 'Webber, Matthew J.', 'Kowalski, Piotr S.', 'Heartlein, Michael W.', 'DeRosa, Frank', 'Anderson, Daniel G.']",,,,
,PMC,"Acquisition of a High Diversity of Bacteria during the Hajj Pilgrimage, Including Acinetobacter baumannii with bla(OXA-72) and Escherichia coli with bla(NDM-5) Carbapenemase Genes",http://dx.doi.org/10.1128/AAC.00669-16,PMC5038294,,,"Pilgrims returning from the Hajj (pilgrimage to Mecca) can be carriers of multidrug-resistant bacteria (MDR). Pharyngeal and rectal swab samples were collected from 98 pilgrims before and after they traveled to the Hajj in 2014 to investigate the acquisition of MDR bacteria. The bacterial diversity in pharyngeal swab samples was assessed by culture with selective media. There was a significantly higher diversity of bacteria in samples collected after the return from the Hajj than in those collected before (P = 0.0008). Surprisingly, Acinetobacter baumannii strains were isolated from 16 pharyngeal swab samples (1 sample taken during the Hajj and 15 samples taken upon return) and 26 post-Hajj rectal swab samples, while none were isolated from samples taken before the Hajj. Testing of all samples by real-time PCR targeting bla(OXA-51) gave positive results for only 1% of samples taken during the Hajj, 21/90 (23.3%) pharyngeal swab samples taken post-Hajj, and 35/90 (38.9%) rectal swab samples taken post-Hajj. One strain of A. baumannii isolated from the pharynx was resistant to imipenem and harbored a bla(OXA-72) carbapenemase gene. Multilocus sequence typing analysis of 43 A. baumannii isolates revealed a huge diversity of 35 sequence types (STs), among which 18 were novel STs reported for the first time in this study. Moreover, we also found one Escherichia coli isolate, collected from a rectal swab sample from a pilgrim taken after the Hajj, which harbored bla(NDM-5), bla(CTX-M-15), bla(TEM-1), and aadA2 (ST2659 and ST181). In conclusion, pilgrims are at a potential risk of acquiring and transmitting MDR Acinetobacter spp. and carbapenemase-producing Gram-negative bacteria during the Hajj season.",,"['Leangapichart, Thongpan', 'Gautret, Philippe', 'Griffiths, Karolina', 'Belhouchat, Khadidja', 'Memish, Ziad', 'Raoult, Didier', 'Rolain, Jean-Marc']",,,,
,PMC,"Viral Diversity, Prey Preference, and Bartonella Prevalence in Desmodus rotundus in Guatemala",http://dx.doi.org/10.1007/s10393-016-1183-z,PMC5164864,,,"Certain bat species serve as natural reservoirs for pathogens in several key viral families including henipa-, lyssa-, corona-, and filoviruses, which may pose serious threats to human health. The Common Vampire Bat (Desmodus rotundus), due to its abundance, sanguivorous feeding habit involving humans and domestic animals, and highly social behavioral ecology, may have an unusually high potential for interspecies disease transmission. Previous studies have investigated rabies dynamics in D. rotundus, yet the diversity of other viruses, bacteria, and other microbes that these bats may carry remains largely unknown. We screened 396 blood, urine, saliva, and fecal samples from D. rotundus captured in Guatemala for 13 viral families and genera. Positive results were found for rhabdovirus, adenovirus, and herpesvirus assays. We also screened these samples for Bartonella spp. and found that 38% of individuals tested positive. To characterize potential for interspecies transmission associated with feeding behavior, we also analyzed cytochrome B sequences from fecal samples to identify prey species and found that domestic cattle (Bos taurus) made up the majority of blood meals. Our findings suggest that the risk of pathogen spillover from Desmodus rotundus, including between domestic animal species, is possible and warrants further investigation to characterize this microbial diversity and expand our understanding of foraging ecology in their populations.",,"['Wray, Amy K.', 'Olival, Kevin J.', 'Morán, David', 'Lopez, Maria Renee', 'Alvarez, Danilo', 'Navarrete-Macias, Isamara', 'Liang, Eliza', 'Simmons, Nancy B.', 'Lipkin, W. Ian', 'Daszak, Peter', 'Anthony, Simon J.']",,,,
,PMC,Rapid Development of a DNA Vaccine for Zika Virus,http://dx.doi.org/10.1126/science.aai9137,PMC5304212,,,"Zika virus (ZIKV) was identified as a cause of congenital disease during an explosive outbreak in the Americas and Caribbean in 2015. Because of the ongoing fetal risk from endemic disease and travel-related exposures, a vaccine to prevent viremia in women of child-bearing age and their partners is imperative. Vaccination with DNA expressing the prM and E proteins of ZIKV was immunogenic in mice and nonhuman primates, and protection against viremia after ZIKV challenge correlated with serum neutralizing activity. These data not only indicate DNA vaccination could be a successful approach to protect against ZIKV infection, but also suggest a protective threshold of vaccine-induced neutralizing activity that will prevent viremia following acute infection.",,"['Dowd, Kimberly A.', 'Ko, Sung-Youl', 'Morabito, Kaitlyn M.', 'Yang, Eun Sung', 'Pelc, Rebecca S.', 'DeMaso, Christina R.', 'Castilho, Leda R.', 'Abbink, Peter', 'Boyd, Michael', 'Nityanandam, Ramya', 'Gordon, David N.', 'Gallagher, John', 'Chen, Xuejun', 'Todd, John-Paul', 'Tsybovsky, Yaroslav', 'Harris, Audray', 'Huang, Yan-Jang S.', 'Higgs, Stephen', 'Vanlandingham, Dana L.', 'Andersen, Hanne', 'Lewis, Mark G.', 'De La Barrera, Rafael', 'Eckels, Kenneth H.', 'Jarman, Richard G.', 'Nason, Martha C.', 'Barouch, Dan H.', 'Roederer, Mario', 'Kong, Wing-Pui', 'Mascola, John R.', 'Pierson, Theodore C.', 'Graham, Barney S.']",,,,
,PMC,Experiences and Psychosocial Impact of West Africa Ebola Deployment on US Health Care Volunteers,http://dx.doi.org/10.1371/currents.outbreaks.c7afaae124e35d2da39ee7e07291b6b5,PMC5074701,27803840,CC BY,"Background: This qualitative study was designed to assess health care volunteers’ experiences and psychosocial impacts associated with deployment to the West Africa Ebola epidemic. Methods: In 2015, using snowball sampling, 16 US health care volunteers who had recently returned from West Africa were recruited for this study. Semi-structured interviews were conducted to collect information associated with each phase of deployment (pre, peri, and post). Results: Participants reported that they were motivated to volunteer because of a sense of responsibility and feelings of empathy and altruism. Immediately prior to deployment, most reported fear of contagion and death, as well as doubts regarding the adequacy of their training. Family members and close friends expressed high levels of concern regarding participants’ decisions to volunteer. During the deployment, participants were fearful of exposure and reported feeling emotionally and physically exhausted. They also reported feeling frustrated by extreme resource limitations, poor management of the mission, lack of clearly defined roles and responsibilities, and inability to provide high quality care. Upon return home, participants felt a sense of isolation, depression, stigmatization, interpersonal difficulties, and extreme stress. Conclusion: Preparedness of volunteers was suboptimal at each stage of deployment. All stakeholders, including volunteers, sponsoring organizations, government agencies, and professional organizations have a shared responsibility in ensuring that volunteers to medical missions are adequately prepared. This is especially critical for high risk deployments. Effective policies and practices need to be developed and implemented in order to protect the health and well-being of health care volunteers to the fullest extent possible.",2016 Sep 21,"['Gershon, Robyn', 'Dernehl, Liza A.', 'Nwankwo, Ezinne', 'Zhi, Qi', 'Qureshi, Kristine']",PLoS Curr,,,
,PMC,The Differential Effects of Alcohol and Nicotine-Specific Nitrosamine Ketone on White Matter Ultrastructure,http://dx.doi.org/10.1093/alcalc/agw067,PMC6075461,,,"AIMS: The chronic consumption of alcohol is known to result in neurodegeneration and impairment of cognitive function. Pathological and neuroimaging studies have confirmed that brain atrophy in alcoholics is mainly due to widespread white matter (WM) loss with neuronal loss restricted to specific regions, such as the prefrontal cortex. Neuroimaging studies of cigarette smokers also suggest that chronic inhalation of tobacco smoke leads to brain atrophy, although the neurotoxic component is unknown. As a high proportion of chronic alcoholics also smoke cigarettes it has been hypothesized that at least some alcohol-related brain damage is due to tobacco smoke exposure. METHODS: 39 Long Evans rats were subjected to 8 weeks exposure to alcohol and/or 5 weeks co-exposure to nicotine-specific nitrosamine ketone (NNK), a proxy for tobacco smoke. Their frontal WM was then assayed with transmission electron microscopy. RESULTS: NNK and ethanol co-exposure had a synergistic effect in decreasing myelinated fibre density. Furthermore, NNK treatment led to a greater reduction in myelin sheath thickness than ethanol whereas only the ethanol-treated animals showed a decrease in unmyelinated fibre density. CONCLUSION: These data suggest that NNK causes WM degeneration, an effect that is exacerbated by alcohol, but unlike alcohol, it has little impact on the neuronal components of the brain.",,"['Papp-Peka, A.', 'Tong, M.', 'Kril, J.J.', 'De La Monte, S.M.', 'Sutherland, G.T.']",,,,
,PMC,Recent advancements in combination subunit vaccine development,http://dx.doi.org/10.1080/21645515.2016.1229719,PMC5287306,,,"Viral structural proteins share a common nature of homotypic interactions that drive viral capsid formation. This natural process has been mimicked in vitro through recombinant technology to generate various virus-like particles (VLPs) and small subviral particles that exhibit similar structural and antigenic properties of their authentic viruses. Therefore, such self-assembled, polyvalent, and highly immunogenic VLPs and small subviral particles are excellent subunit vaccines against individual viruses, such as the VLP vaccines against the hepatitis B virus, human papilloma virus, and hepatitis E virus, which have already been in the markets. In addition, various antigens and epitopes can be fused with VLPs, small subviral particles, or protein polymers, forming chimeric mono-, bi-, or trivalent vaccines. Owing to their easy-production, un-infectiousness, and polyvalence, the recombinant, chimeric vaccines offer a new approach for development of safe, low-cost, and high efficient subunit vaccines against a single or more pathogens or diseases. While the first VLP-based combination vaccine against malaria has been approved for human use, many others are under development with promising future, which are summarized in this commentary.",,"['Tan, Ming', 'Jiang, Xi']",,,,
,PMC,Understanding bat SARS-like coronaviruses for the preparation of future coronavirus outbreaks — Implications for coronavirus vaccine development,http://dx.doi.org/10.1080/21645515.2016.1228500,PMC5287300,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) first emerged in 2003, causing the SARS epidemic which resulted in a 10% fatality rate. The advancements in metagenomic techniques have allowed the identification of SARS-like coronaviruses (SL-CoVs) sequences that share high homology to the human SARS-CoV epidemic strains from wildlife bats, presenting concrete evidence that bats are the origin and natural reservoir of SARS-CoV. The application of reverse genetics further enabled that characterization of these bat CoVs and the prediction of their potential to cause disease in humans. The knowledge gained from such studies is valuable in the surveillance and preparation of a possible future outbreak caused by a spill-over of these bat SL-CoVs.",,"['Ng, Oi-Wing', 'Tan, Yee-Joo']",,,,
,PMC,Activated GL7(+) B cells are maintained within the inflamed CNS in the absence of follicle formation during viral encephalomyelitis,http://dx.doi.org/10.1016/j.bbi.2016.09.022,PMC5215090,,,"Central nervous system (CNS) inflammation associated with viral infection and autoimmune disease results in the accumulation of B cells in various differentiation stages. However, the contribution between peripheral and CNS activation remains unclear. During gliatropic coronavirus induced encephalomyelitis, accumulation of protective antibody secreting cells is preceded by infiltration of B cells with a naïve and early differentiation phenotype (Phares et al., 2014). Investigation of the temporal dynamics of B cell activation in draining cervical lymph nodes (CLN) and the CNS revealed that peak CNS infiltration of early activated, unswitched IgD(+) and IgM(+) B cells coincided with polyclonal activation in CLN. By contrast, isotype-switched IgG(+) B cells did not accumulate until peripheral germinal center formation. In the CNS, unswitched B cells were confined to the perivascular space and meninges, with only rare B cell clusters, while isotype-switched B cells localized to parenchymal areas. Although ectopic follicle formation was not observed, more differentiated B cell subsets within the CNS expressed the germinal center marker GL7, albeit at lower levels than CLN counterparts. During chronic infection, CNS IgD(int) and IgD(−) B cell subsets further displayed sustained markers of proliferation and CD4 T cell help, which were only transiently expressed in the CLN. A contribution of local CD4 T cell help to sustain B cell activation was supported by occasional B cells adjacent to T cells. The results suggest that accumulation of differentiated B cell subsets within the CNS is largely dictated by peripheral activation, but that local events contribute to their sustained activation independent of ectopic follicle formation.",,"['DiSano, Krista D.', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.']",,,,
,PMC,Infectivity of attenuated poxvirus vaccine vectors and immunogenicity of a raccoonpox vectored rabies vaccine in the Brazilian Free-tailed bat (Tadarida brasiliensis),http://dx.doi.org/10.1016/j.vaccine.2016.08.088,PMC5543807,,,"Bats (Order Chiroptera) are an abundant group of mammals with tremendous ecological value as insectivores and plant dispersers, but their role as reservoirs of zoonotic diseases has received more attention in the last decade. With the goal of managing disease in free-ranging bats, we tested modified vaccinia Ankara (MVA) and raccoon poxvirus (RCN) as potential vaccine vectors in the Brazilian Free-tailed bat (Tadarida brasiliensis), using biophotonic in vivo imaging and immunogenicity studies. Animals were administered recombinant poxviral vectors expressing the luciferase gene (MVA-luc, RCN-luc) through oronasal (ON) or intramuscular (IM) routes and subsequently monitored for bioluminescent signal indicative of viral infection. No clinical illness was noted after exposure to any of the vectors, and limited luciferase expression was observed. Higher and longer levels of expression were observed with the RCN-luc construct. When given IM, luciferase expression was limited to the site of injection, while ON exposure led to initial expression in the oral cavity, often followed by secondary replication at another location, likely the gastric mucosa or gastric associated lymphatic tissue. Viral DNA was detected in oral swabs up to 7 and 9 days post infection (dpi) for MVA and RCN, respectively. While no live virus was detected in oral swabs from MVA-infected bats, titers up to 3.88 × 10(4) PFU/ml were recovered from oral swabs of RCN-infected bats. Viral DNA was also detected in fecal samples from two bats inoculated IM with RCN, but no live virus was recovered. Finally, we examined the immunogenicity of a RCN based rabies vaccine (RCN-G) following ON administration. Significant rabies neutralizing antibody titers were detected in the serum of immunized bats using the rapid fluorescence focus inhibition test (RFFIT). These studies highlight the safety and immunogenicity of attenuated poxviruses and their potential use as vaccine vectors in bats.",,"['Stading, Ben R.', 'Osorio, Jorge E.', 'Velasco-Villa, Andres', 'Smotherman, Michael', 'Kingstad-Bakke, Brock', 'Rocke, Tonie E.']",,,,
,PMC,The unfolded protein response controls ER stress-induced apoptosis of lung epithelial cells through angiotensin generation,http://dx.doi.org/10.1152/ajplung.00449.2015,PMC5130534,,,"Recent work from this laboratory showed that endoplasmic reticulum (ER) stress-induced apoptosis of alveolar epithelial cells (AECs) is regulated by the autocrine angiotensin (ANG)II/ANG1-7 system. The proteasome inhibitor MG132 or surfactant protein C (SP-C) BRICHOS domain mutation G100S induced apoptosis in human AECs by activating the proapoptotic cathepsin D and reducing antiapoptotic angiotensin converting enzyme-2 (ACE-2). This study tested the hypothesis that ER stress-induced apoptosis of human AECs might be mediated by influence of the unfolded protein response (UPR) on the autocrine ANGII/ANG1-7 system. A549 cells were challenged with MG132 or SP-C BRICHOS domain mutant G100S to induce ER stress and activation of UPR pathways. The results showed that either MG132 or G100S SP-C mutation activated all three canonical pathways of the UPR (IRE1/XBP1, ATF6, and PERK/eIF2α), which led to a significant increase in cathepsin D or in TACE (an ACE-2 ectodomain shedding enzyme) and eventually caused AEC apoptosis. However, ER stress-induced AEC apoptosis could be prevented by chemical chaperone or by UPR blockers. It is also suggested that ATF6 and IRE1 pathways might play important role in regulation of angiotensin system. These data demonstrate that ER stress induces apoptosis in human AECs through mediation of UPR pathways, which in turn regulate the autocrine ANGII/ANG1-7 system. They also demonstrated that ER stress-induced AEC apoptosis can be blocked by inhibition of UPR signaling pathways.",,"['Nguyen, Hang', 'Uhal, Bruce D.']",,,,
,PMC,"Enteric immunity, the gut microbiome, and sepsis: Rethinking the germ theory of disease",http://dx.doi.org/10.1177/1535370216669610,PMC5167116,,,"Sepsis is a poorly understood syndrome of systemic inflammation responsible for hundreds of thousands of deaths every year. The integrity of the gut epithelium and competence of adaptive immune responses are notoriously compromised during sepsis, and the prevalent assumption in the scientific and medical community is that intestinal commensals have a detrimental role in the systemic inflammation and susceptibility to nosocomial infections seen in critically ill, septic patients. However, breakthroughs in the last decade provide strong credence to the idea that our mucosal microbiome plays an essential role in adaptive immunity, where a human host and its prokaryotic colonists seem to exist in a carefully negotiated armistice with compromises and benefits that go both ways. In this review, we re-examine the notion that intestinal contents are the driving force of critical illness. An overview of the interaction between the microbiome and the immune system is provided, with a special focus on the impact of commensals in priming and the careful balance between normal intestinal flora and pathogenic organisms residing in the gut microbiome. Based on the data in hand, we hypothesize that sepsis induces imbalances in microbial populations residing in the gut, along with compromises in epithelial integrity. As a result, normal antigen sampling becomes impaired, and proliferative cues are intermixed with inhibitory signals. This situates the microbiome, the gut, and its complex immune network of cells and bacteria, at the center of aberrant immune responses during and after sepsis.",,"['Cabrera-Perez, Javier', 'Badovinac, Vladimir P', 'Griffith, Thomas S']",,,,
,PMC,"Respiratory Virus–Associated Severe Acute Respiratory Illness and Viral Clustering in Malawian Children in a Setting With a High Prevalence of HIV Infection, Malaria, and Malnutrition",http://dx.doi.org/10.1093/infdis/jiw426,PMC5341080,,,"BACKGROUND: We used data from 4 years of pediatric severe acute respiratory illness (SARI) sentinel surveillance in Blantyre, Malawi, to identify factors associated with clinical severity and coviral clustering. METHODS: From January 2011 to December 2014, 2363 children aged 3 months to 14 years presenting to the hospital with SARI were enrolled. Nasopharyngeal aspirates were tested for influenza virus and other respiratory viruses. We assessed risk factors for clinical severity and conducted clustering analysis to identify viral clusters in children with viral codetection. RESULTS: Hospital-attended influenza virus–positive SARI incidence was 2.0 cases per 10 000 children annually; it was highest among children aged <1 year (6.3 cases per 10 000), and human immunodeficiency virus (HIV)–infected children aged 5–9 years (6.0 cases per 10 000). A total of 605 SARI cases (26.8%) had warning signs, which were positively associated with HIV infection (adjusted risk ratio [aRR], 2.4; 95% confidence interval [CI], 1.4–3.9), respiratory syncytial virus infection (aRR, 1.9; 95% CI, 1.3–3.0) and rainy season (aRR, 2.4; 95% CI, 1.6–3.8). We identified 6 coviral clusters; 1 cluster was associated with SARI with warning signs. CONCLUSIONS: Influenza vaccination may benefit young children and HIV-infected children in this setting. Viral clustering may be associated with SARI severity; its assessment should be included in routine SARI surveillance.",,"['Peterson, Ingrid', 'Bar-Zeev, Naor', 'Kennedy, Neil', 'Ho, Antonia', 'Newberry, Laura', 'SanJoaquin, Miguel A.', 'Menyere, Mavis', 'Alaerts, Maaike', 'Mapurisa, Gugulethu', 'Chilombe, Moses', 'Mambule, Ivan', 'Lalloo, David G.', 'Anderson, Suzanne T.', 'Katangwe, Thembi', 'Cunliffe, Nigel', 'Nagelkerke, Nico', 'McMorrow, Meredith', 'Widdowson, Marc-Allain', 'French, Neil', 'Everett, Dean', 'Heyderman, Robert S.']",,,,
,PMC,Letter from the editor,http://dx.doi.org/10.1080/21645515.2016.1228365,PMC5027697,,,,,,,,,
,PMC,An RNA Element That Facilitates Programmed Ribosomal Readthrough in Turnip Crinkle Virus Adopts Multiple Conformations,http://dx.doi.org/10.1128/JVI.01129-16,PMC5021432,,,"Ribosome recoding is used by RNA viruses for translational readthrough or frameshifting past termination codons for the synthesis of extension products. Recoding sites, along with downstream recoding stimulatory elements (RSEs), have long been studied in reporter constructs, because these fragments alone mediate customary levels of recoding and are thus assumed to contain complete instructions for establishment of the proper ratio of termination to recoding. RSEs from the Tombusviridae and Luteoviridae are thought to be exceptions, since they contain a long-distance RNA-RNA connection with the 3′ end. This interaction has been suggested to substitute for pseudoknots, thought to be missing in tombusvirid RSEs. We provide evidence that the phylogenetically conserved RSE of the carmovirus Turnip crinkle virus (TCV) adopts an alternative, smaller structure that extends an upstream conserved hairpin and that this alternative structure is the predominant form of the RSE within nascent viral RNA in plant cells and when RNA is synthesized in vitro. The TCV RSE also contains an internal pseudoknot along with the long-distance interaction, and the pseudoknot is not compatible with the phylogenetically conserved structure. Conserved residues just past the recoding site are important for recoding, and these residues are also conserved in the RSEs of gammaretroviruses. Our data demonstrate the dynamic nature of the TCV RSE and suggest that studies using reporter constructs may not be effectively recapitulating RSE-mediated recoding within viral genomes. IMPORTANCE Ribosome recoding is used by RNA viruses to enable ribosomes to extend translation past termination codons for the synthesis of longer products. Recoding sites and a downstream recoding stimulatory element (RSE) mediate expected levels of recoding when excised and placed in reporter constructs and thus are assumed to contain complete instructions for the establishment of the proper ratio of termination to recoding. We provide evidence that most of the TCV RSE adopts an alternative structure that extends an upstream conserved hairpin and that this alternative structure, and not the phylogenetically conserved structure, is the predominant form of the RSE in RNA synthesized in vitro and in plant cells. The TCV RSE also contains an internal pseudoknot that is not compatible with the phylogenetically conserved structure and an RNA bridge to the 3′ end. These data suggest that the TCV RSE is structurally dynamic and that multiple conformations are likely required to regulate ribosomal readthrough.",,"['Kuhlmann, Micki M.', 'Chattopadhyay, Maitreyi', 'Stupina, Vera A.', 'Gao, Feng', 'Simon, Anne E.']",,,,
,PMC,An Ebola Virus-Like Particle-Based Reporter System Enables Evaluation of Antiviral Drugs In Vivo under Non-Biosafety Level 4 Conditions,http://dx.doi.org/10.1128/JVI.01239-16,PMC5021419,,,"Ebola virus (EBOV) is a highly contagious lethal pathogen. As a biosafety level 4 (BSL-4) agent, however, EBOV is restricted to costly BSL-4 laboratories for experimentation, thus significantly impeding the evaluation of EBOV vaccines and drugs. Here, we report an EBOV-like particle (EBOVLP)-based luciferase reporter system that enables the evaluation of anti-EBOV agents in vitro and in vivo outside BSL-4 facilities. Cotransfection of HEK293T cells with four plasmids encoding the proteins VP40, NP, and GP of EBOV and firefly luciferase (Fluc) resulted in the production of Fluc-containing filamentous particles that morphologically resemble authentic EBOV. The reporter EBOVLP was capable of delivering Fluc into various cultured cells in a GP-dependent manner and was recognized by a conformation-dependent anti-EBOV monoclonal antibody (MAb). Significantly, inoculation of mice with the reporter EBOVLP led to the delivery of Fluc protein into target cells and rapid generation of intense bioluminescence signals that could be blocked by the administration of EBOV neutralizing MAbs. This BSL-4-free reporter system should facilitate high-throughput screening for anti-EBOV drugs targeting viral entry and efficacy testing of candidate vaccines. IMPORTANCE Ebola virus (EBOV) researches have been limited to costly biosafety level 4 (BSL-4) facilities due to the lack of animal models independent of BSL-4 laboratories. In this study, we reveal that a firefly luciferase-bearing EBOV-like particle (EBOVLP) with typical filamentous EBOV morphology is capable of delivering the reporter protein into murine target cells both in vitro and in vivo. Moreover, we demonstrate that the reporter delivery can be inhibited both in vitro and in vivo by a known anti-EBOV protective monoclonal antibody, 13C6. Our work provides a BSL-4-free system that can facilitate the in vivo evaluation of anti-EBOV antibodies, drugs, and vaccines. The system may also be useful for mechanistic study of the viral entry process.",,"['Li, Dapeng', 'Chen, Tan', 'Hu, Yang', 'Zhou, Yu', 'Liu, Qingwei', 'Zhou, Dongming', 'Jin, Xia', 'Huang, Zhong']",,,,
,PMC,Replication of Human Norovirus RNA in Mammalian Cells Reveals Lack of Interferon Response,http://dx.doi.org/10.1128/JVI.01425-16,PMC5021416,,,"Human noroviruses (HuNoVs), named after the prototype strain Norwalk virus (NV), are a leading cause of acute gastroenteritis outbreaks worldwide. Studies on the related murine norovirus (MNV) have demonstrated the importance of an interferon (IFN) response in host control of virus replication, but this remains unclear for HuNoVs. Despite the lack of an efficient cell culture infection system, transfection of stool-isolated NV RNA into mammalian cells leads to viral RNA replication and virus production. Using this system, we show here that NV RNA replication is sensitive to type I (α/β) and III (interleukin-29 [IL-29]) IFN treatment. However, in cells capable of a strong IFN response to Sendai virus (SeV) and poly(I·C), NV RNA replicates efficiently and generates double-stranded RNA without inducing a detectable IFN response. Replication of HuNoV genogroup GII.3 strain U201 RNA, generated from a reverse genetics system, also does not induce an IFN response. Consistent with a lack of IFN induction, NV RNA replication is enhanced neither by neutralization of type I/III IFNs through neutralizing antibodies or the soluble IFN decoy receptor B18R nor by short hairpin RNA (shRNA) knockdown of mitochondrial antiviral signaling protein (MAVS) or interferon regulatory factor 3 (IRF3) in the IFN induction pathways. In contrast to other positive-strand RNA viruses that block IFN induction by targeting MAVS for degradation, MAVS is not degraded in NV RNA-replicating cells, and an SeV-induced IFN response is not blocked. Together, these results indicate that HuNoV RNA replication in mammalian cells does not induce an IFN response, suggesting that the epithelial IFN response may play a limited role in host restriction of HuNoV replication. IMPORTANCE Human noroviruses (HuNoVs) are a leading cause of epidemic gastroenteritis worldwide. Due to lack of an efficient cell culture system and robust small-animal model, little is known about the innate host defense to these viruses. Studies on murine norovirus (MNV) have shown the importance of an interferon (IFN) response in host control of MNV replication, but this remains unclear for HuNoVs. Here, we investigated the IFN response to HuNoV RNA replication in mammalian cells using Norwalk virus stool RNA transfection, a reverse genetics system, IFN neutralization reagents, and shRNA knockdown methods. Our results show that HuNoV RNA replication in mammalian epithelial cells does not induce an IFN response, nor can it be enhanced by blocking the IFN response. These results suggest a limited role of the epithelial IFN response in host control of HuNoV RNA replication, providing important insights into our understanding of the host defense to HuNoVs that differs from that to MNV.",,"['Qu, Lin', 'Murakami, Kosuke', 'Broughman, James R.', 'Lay, Margarita K.', 'Guix, Susana', 'Tenge, Victoria R.', 'Atmar, Robert L.', 'Estes, Mary K.']",,,,
,PMC,Viral Macro Domains Reverse Protein ADP-Ribosylation,http://dx.doi.org/10.1128/JVI.00705-16,PMC5021415,,,"ADP-ribosylation is a posttranslational protein modification in which ADP-ribose is transferred from NAD(+) to specific acceptors to regulate a wide variety of cellular processes. The macro domain is an ancient and highly evolutionarily conserved protein domain widely distributed throughout all kingdoms of life, including viruses. The human TARG1/C6orf130, MacroD1, and MacroD2 proteins can reverse ADP-ribosylation by acting on ADP-ribosylated substrates through the hydrolytic activity of their macro domains. Here, we report that the macro domain from hepatitis E virus (HEV) serves as an ADP-ribose-protein hydrolase for mono-ADP-ribose (MAR) and poly(ADP-ribose) (PAR) chain removal (de-MARylation and de-PARylation, respectively) from mono- and poly(ADP)-ribosylated proteins, respectively. The presence of the HEV helicase in cis dramatically increases the binding of the macro domain to poly(ADP-ribose) and stimulates the de-PARylation activity. Abrogation of the latter dramatically decreases replication of an HEV subgenomic replicon. The de-MARylation activity is present in all three pathogenic positive-sense, single-stranded RNA [(+)ssRNA] virus families which carry a macro domain: Coronaviridae (severe acute respiratory syndrome coronavirus and human coronavirus 229E), Togaviridae (Venezuelan equine encephalitis virus), and Hepeviridae (HEV), indicating that it might be a significant tropism and/or pathogenic determinant. IMPORTANCE Protein ADP-ribosylation is a covalent posttranslational modification regulating cellular protein activities in a dynamic fashion to modulate and coordinate a variety of cellular processes. Three viral families, Coronaviridae, Togaviridae, and Hepeviridae, possess macro domains embedded in their polyproteins. Here, we show that viral macro domains reverse cellular ADP-ribosylation, potentially cutting the signal of a viral infection in the cell. Various poly(ADP-ribose) polymerases which are notorious guardians of cellular integrity are demodified by macro domains from members of these virus families. In the case of hepatitis E virus, the adjacent viral helicase domain dramatically increases the binding of the macro domain to PAR and simulates the demodification activity.",,"['Li, Changqing', 'Debing, Yannick', 'Jankevicius, Gytis', 'Neyts, Johan', 'Ahel, Ivan', 'Coutard, Bruno', 'Canard, Bruno']",,,,
,PMC,Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion,http://dx.doi.org/10.1128/JVI.01429-16,PMC5021412,,,"The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) cause significant morbidity and morality. There is currently no approved therapeutic for highly pathogenic coronaviruses, even as MERS-CoV is spreading throughout the Middle East. We previously screened a library of FDA-approved drugs for inhibitors of coronavirus replication in which we identified Abelson (Abl) kinase inhibitors, including the anticancer drug imatinib, as inhibitors of both SARS-CoV and MERS-CoV in vitro. Here we show that the anti-CoV activity of imatinib occurs at the early stages of infection, after internalization and endosomal trafficking, by inhibiting fusion of the virions at the endosomal membrane. We specifically identified the imatinib target, Abelson tyrosine-protein kinase 2 (Abl2), as required for efficient SARS-CoV and MERS-CoV replication in vitro. These data demonstrate that specific approved drugs can be characterized in vitro for their anticoronavirus activity and used to identify host proteins required for coronavirus replication. This type of study is an important step in the repurposing of approved drugs for treatment of emerging coronaviruses. IMPORTANCE Both SARS-CoV and MERS-CoV are zoonotic infections, with bats as the primary source. The 2003 SARS-CoV outbreak began in Guangdong Province in China and spread to humans via civet cats and raccoon dogs in the wet markets before spreading to 37 countries. The virus caused 8,096 confirmed cases of SARS and 774 deaths (a case fatality rate of ∼10%). The MERS-CoV outbreak began in Saudi Arabia and has spread to 27 countries. MERS-CoV is believed to have emerged from bats and passed into humans via camels. The ongoing outbreak of MERS-CoV has resulted in 1,791 cases of MERS and 640 deaths (a case fatality rate of 36%). The emergence of SARS-CoV and MERS-CoV provides evidence that coronaviruses are currently spreading from zoonotic sources and can be highly pathogenic, causing serious morbidity and mortality in humans. Treatment of SARS-CoV and MERS-CoV infection is limited to providing supportive therapy consistent with any serious lung disease, as no specific drugs have been approved as therapeutics. Highly pathogenic coronaviruses are rare and appear to emerge and disappear within just a few years. Currently, MERS-CoV is still spreading, as new infections continue to be reported. The outbreaks of SARS-CoV and MERS-CoV and the continuing diagnosis of new MERS cases highlight the need for finding therapeutics for these diseases and potential future coronavirus outbreaks. Screening FDA-approved drugs streamlines the pipeline for this process, as these drugs have already been tested for safety in humans.",,"['Coleman, Christopher M.', 'Sisk, Jeanne M.', 'Mingo, Rebecca M.', 'Nelson, Elizabeth A.', 'White, Judith M.', 'Frieman, Matthew B.']",,,,
,PMC,The Interferon-Stimulated Gene IFITM3 Restricts Infection and Pathogenesis of Arthritogenic and Encephalitic Alphaviruses,http://dx.doi.org/10.1128/JVI.00655-16,PMC5021394,,,"Host cells respond to viral infections by producing type I interferon (IFN), which induces the expression of hundreds of interferon-stimulated genes (ISGs). Although ISGs mediate a protective state against many pathogens, the antiviral functions of the majority of these genes have not been identified. IFITM3 is a small transmembrane ISG that restricts a broad range of viruses, including orthomyxoviruses, flaviviruses, filoviruses, and coronaviruses. Here, we show that alphavirus infection is increased in Ifitm3(−/−) and Ifitm locus deletion (Ifitm-del) fibroblasts and, reciprocally, reduced in fibroblasts transcomplemented with Ifitm3. Mechanistic studies showed that Ifitm3 did not affect viral binding or entry but inhibited pH-dependent fusion. In a murine model of chikungunya virus arthritis, Ifitm3(−/−) mice sustained greater joint swelling in the ipsilateral ankle at days 3 and 7 postinfection, and this correlated with higher levels of proinflammatory cytokines and viral burden. Flow cytometric analysis suggested that Ifitm3(−/−) macrophages from the spleen were infected at greater levels than observed in wild-type (WT) mice, results that were supported by experiments with Ifitm3(−/−) bone marrow-derived macrophages. Ifitm3(−/−) mice also were more susceptible than WT mice to lethal alphavirus infection with Venezuelan equine encephalitis virus, and this was associated with greater viral burden in multiple organs. Collectively, our data define an antiviral role for Ifitm3 in restricting infection of multiple alphaviruses. IMPORTANCE The interferon-induced transmembrane protein 3 (IFITM3) inhibits infection of multiple families of viruses in cell culture. Compared to other viruses, much less is known about the antiviral effect of IFITM3 on alphaviruses. In this study, we characterized the antiviral activity of mouse Ifitm3 against arthritogenic and encephalitic alphaviruses using cells and animals with a targeted gene deletion of Ifitm3 as well as deficient cells transcomplemented with Ifitm3. Based on extensive virological analysis, we demonstrate greater levels of alphavirus infection and disease pathogenesis when Ifitm3 expression is absent. Our data establish an inhibitory role for Ifitm3 in controlling infection of alphaviruses.",,"['Poddar, Subhajit', 'Hyde, Jennifer L.', 'Gorman, Matthew J.', 'Farzan, Michael', 'Diamond, Michael S.']",,,,
,PMC,Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy,http://dx.doi.org/10.1038/nsmb.3293,PMC5515730,,,"The threat of a major coronavirus pandemic urges the development of suitable strategies to combat these pathogens. HCoV-NL63 is an α-coronavirus that can cause severe lower respiratory tract infections requiring hospitalization. We report here the 3.4 Å resolution cryo-electron microscopy reconstruction of the HCoV-NL63 coronavirus spike glycoprotein trimer, which is the conformational machine responsible for entry into host cells and the sole target of neutralizing antibodies during infection. The map resolves the extensive glycan shield obstructing the protein surface and, in combination with mass-spectrometry, provides a structural framework to understand accessibility to antibodies. The structure also reveals a remarkable modular architecture of the receptor-binding subunit and the complete architecture of the fusion machinery including the triggering loop and the C-terminal domains, which contribute to anchoring the trimer to the viral membrane. Our data further suggest that HCoV-NL63 and other coronaviruses use molecular trickery, based on masking of epitopes with glycans and activating conformational changes, to evade the immune system of infected hosts.",,"['Walls, Alexandra C.', 'Tortorici, M. Alejandra', 'Frenz, Brandon', 'Snijder, Joost', 'Li, Wentao', 'Rey, Félix A.', 'DiMaio, Frank', 'Bosch, Berend-Jan', 'Veesler, David']",,,,
,PMC,Viral and Cellular mRNA Translation in Coronavirus-Infected Cells,http://dx.doi.org/10.1016/bs.aivir.2016.08.001,PMC5388242,,,"Coronaviruses have large positive-strand RNA genomes that are 5′ capped and 3′ polyadenylated. The 5′-terminal two-thirds of the genome contain two open reading frames (ORFs), 1a and 1b, that together make up the viral replicase gene and encode two large polyproteins that are processed by viral proteases into 15–16 nonstructural proteins, most of them being involved in viral RNA synthesis. ORFs located in the 3′-terminal one-third of the genome encode structural and accessory proteins and are expressed from a set of 5′ leader-containing subgenomic mRNAs that are synthesized by a process called discontinuous transcription. Coronavirus protein synthesis not only involves cap-dependent translation mechanisms but also employs regulatory mechanisms, such as ribosomal frameshifting. Coronavirus replication is known to affect cellular translation, involving activation of stress-induced signaling pathways, and employing viral proteins that affect cellular mRNA translation and RNA stability. This chapter describes our current understanding of the mechanisms involved in coronavirus mRNA translation and changes in host mRNA translation observed in coronavirus-infected cells.",,"['Nakagawa, K.', 'Lokugamage, K.G.', 'Makino, S.']",,,,
,PMC,"Risks of Death and Severe Disease in Patients With Middle East Respiratory Syndrome Coronavirus, 2012–2015",http://dx.doi.org/10.1093/aje/kww013,PMC5023790,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen, first recognized in 2012, with a high case fatality risk, no vaccine, and no treatment beyond supportive care. We estimated the relative risks of death and severe disease among MERS-CoV patients in the Middle East between 2012 and 2015 for several risk factors, using Poisson regression with robust variance and a bootstrap-based expectation maximization algorithm to handle extensive missing data. Increased age and underlying comorbidity were risk factors for both death and severe disease, while cases arising in Saudi Arabia were more likely to be severe. Cases occurring later in the emergence of MERS-CoV and among health-care workers were less serious. This study represents an attempt to estimate risk factors for an emerging infectious disease using open data and to address some of the uncertainty surrounding MERS-CoV epidemiology.",,"['Rivers, Caitlin M.', 'Majumder, Maimuna S.', 'Lofgren, Eric T.']",,,,
,PMC,Natural mutations in IFITM3 modulate post‐translational regulation and toggle antiviral specificity,http://dx.doi.org/10.15252/embr.201642771,PMC5090704,,,"The interferon‐induced transmembrane (IFITM) proteins protect host cells from diverse virus infections. IFITM proteins also incorporate into HIV‐1 virions and inhibit virus fusion and cell‐to‐cell spread, with IFITM3 showing the greatest potency. Here, we report that amino‐terminal mutants of IFITM3 preventing ubiquitination and endocytosis are more abundantly incorporated into virions and exhibit enhanced inhibition of HIV‐1 fusion. An analysis of primate genomes revealed that IFITM3 is the most ancient antiviral family member of the IFITM locus and has undergone a repeated duplication in independent host lineages. Some IFITM3 genes in nonhuman primates, including those that arose following gene duplication, carry amino‐terminal mutations that modify protein localization and function. This suggests that “runaway” IFITM3 variants could be selected for altered antiviral activity. Furthermore, we show that adaptations in IFITM3 result in a trade‐off in antiviral specificity, as variants exhibiting enhanced activity against HIV‐1 poorly restrict influenza A virus. Overall, we provide the first experimental evidence that diversification of IFITM3 genes may boost the antiviral coverage of host cells and provide selective functional advantages.",,"['Compton, Alex A', 'Roy, Nicolas', 'Porrot, Françoise', 'Billet, Anne', 'Casartelli, Nicoletta', 'Yount, Jacob S', 'Liang, Chen', 'Schwartz, Olivier']",,,,
,PMC,α-Helical Coiled Coil Peptide Materials for Biomedical Applications,http://dx.doi.org/10.1002/wnan.1424,PMC5300935,,,"Self-assembling coiled coils, which occur commonly in native proteins, have received significant interest for the design of new biomaterials-based medical therapies. Considerable effort over recent years has led to a detailed understanding of the self-assembly process of coiled coils, and a diverse collection of strategies have been developed for designing functional materials using this motif. The ability to engineer the interface between coiled coils allows one to achieve variously connected components, leading to precisely defined structures such as nanofibers, nanotubes, nanoparticles, networks, gels, and combinations of these. Currently these materials are being developed for a range of biotechnological and medical applications, including drug delivery systems for controlled release, targeted nanomaterials, “drug-free” therapeutics, vaccine delivery systems, and others.",,"['Wu, Yaoying', 'Collier, Joel H.']",,,,
,PMC,Update on novel targets and potential treatment avenues in pulmonary hypertension,http://dx.doi.org/10.1152/ajplung.00302.2016,PMC5130539,,,"Pulmonary hypertension (PH) is a condition marked by a combination of constriction and remodeling within the pulmonary vasculature. It remains a disease without a cure, as current treatments were developed with a focus on vasodilatory properties but do not reverse the remodeling component. Numerous recent advances have been made in the understanding of cellular processes that drive pathologic remodeling in each layer of the vessel wall as well as the accompanying maladaptive changes in the right ventricle. In particular, the past few years have yielded much improved insight into the pathways that contribute to altered metabolism, mitochondrial function, and reactive oxygen species signaling and how these pathways promote the proproliferative, promigratory, and antiapoptotic phenotype of the vasculature during PH. Additionally, there have been significant advances in numerous other pathways linked to PH pathogenesis, such as sex hormones and perivascular inflammation. Novel insights into cellular pathology have suggested new avenues for the development of both biomarkers and therapies that will hopefully bring us closer to the elusive goal: a therapy leading to reversal of disease.",,"['Huetsch, John C.', 'Suresh, Karthik', 'Bernier, Meghan', 'Shimoda, Larissa A.']",,,,
,PMC,A Sensitive DNA Capacitive Biosensor Using Interdigitated Electrodes,http://dx.doi.org/10.1016/j.bios.2016.09.006,PMC5295646,,,"This paper presents a label-free affinity-based capacitive biosensor using interdigitated electrodes. Using an optimized process of DNA probe preparation to minimize the effect of contaminants in commercial thiolated DNA probe, the electrode surface was functionalized with the 24-nucleotide DNA probes based on the West Nile virus sequence (Kunjin strain). The biosensor has the ability to detect complementary DNA fragments with a detection limit down to 20 DNA target molecules (1.5 aM range), making it suitable for a practical point-of-care (POC) platform for low target count clinical applications without the need for amplification. The reproducibility of the biosensor detection was improved with efficient covalent immobilization of purified single-stranded DNA probe oligomers on cleaned gold microelectrodes. In addition to the low detection limit, the biosensor showed a dynamic range of detection from 1 μL(−1) to 10(5) μL(−1) target molecules (20 to 2 million targets), making it suitable for sample analysis in a typical clinical application environment. The binding results presented in this paper were validated using fluorescent oligomers.",,"['Wang, Lei', 'Veselinovic, Milena', 'Yang, Lang', 'Geiss, Brian J.', 'Dandy, David S.', 'Chen, Tom']",,,,
,PMC,Human and Mouse Eosinophils Have Antiviral Activity against Parainfluenza Virus,http://dx.doi.org/10.1165/rcmb.2015-0405OC,PMC5023029,,,"Respiratory viruses cause asthma exacerbations. Because eosinophils are the prominent leukocytes in the airways of 60–70% of patients with asthma, we evaluated the effects of eosinophils on a common respiratory virus, parainfluenza 1, in the lung. Eosinophils recruited to the airways of wild-type mice after ovalbumin sensitization and challenge significantly decreased parainfluenza virus RNA in the lungs 4 days after infection compared with nonsensitized animals. This antiviral effect was also seen in IL-5 transgenic mice with an abundance of airway eosinophils (NJ.1726) but was lost in transgenic eosinophil-deficient mice (PHIL) and in IL-5 transgenic mice crossed with eosinophil-deficient mice (NJ.1726-PHIL). Loss of the eosinophil granule protein eosinophil peroxidase, using eosinophil peroxidase–deficient transgenic mice, did not reduce eosinophils’ antiviral effect. Eosinophil antiviral mechanisms were also explored in vitro. Isolated human eosinophils significantly reduced parainfluenza virus titers. This effect did not involve degradation of viral RNA by eosinophil granule RNases. However, eosinophils treated with a nitric oxide synthase inhibitor lost their antiviral activity, suggesting eosinophils attenuate viral infectivity through production of nitric oxide. Consequently, eosinophil nitric oxide production was measured with an intracellular fluorescent probe. Eosinophils produced nitric oxide in response to virus and to a synthetic agonist of the virus-sensing innate immune receptor, Toll-like receptor (TLR) 7. IFNγ increased expression of eosinophil TLR7 and potentiated TLR7-induced nitric oxide production. These results suggest that eosinophils promote viral clearance in the lung and contribute to innate immune responses against respiratory virus infections in humans.",,"['Drake, Matthew G.', 'Bivins-Smith, Elizabeth R.', 'Proskocil, Becky J.', 'Nie, Zhenying', 'Scott, Gregory D.', 'Lee, James J.', 'Lee, Nancy A.', 'Fryer, Allison D.', 'Jacoby, David B.']",,,,
,PMC,Enteropathogenic Escherichia coli (EPEC) infection in association with acute gastroenteritis in 7 dogs from Saskatchewan,,PMC4982568,,,Seven dogs diagnosed with enteropathogenic Escherichia coli (EPEC) infection in association with acute gastroenteritis are described. Disease severity ranged from mild in adults to fatal disease in young dogs. Enteropathogenic E. coli infection should be considered as a possible differential diagnosis in dogs with diarrhea.,,"['Kjaergaard, Astrid B.', 'Carr, Anthony P.', 'Gaunt, M. Casey']",,,,
,PMC,Treatment of extraskeletal osteosarcoma at a previous injection site resulting in prolonged survival in 1 dog,,PMC4982565,,,"A rare presentation of an extraskeletal osteosarcoma at a previous interscapular injection site in a dog is described. Treatment included surgical excision of the tumor followed by 6 rounds of intravenous carboplatin, oral toceranib, and cyclophosphamide. The dog survived for 20.5 months after diagnosis despite early development of pulmonary metastases.",,"['Selmic, Laura E.', 'Griffin, Lynn R.', 'Rector, Megan H.', 'Lafferty, Mary', 'Pool, Roy', 'Ehrhart, Nicole P.']",,,,
,PMC,Complementing T-cell Function: An Inhibitory Role of the Complement System in T-cell-Mediated Antitumor Immunity.,http://dx.doi.org/10.1158/2159-8290.CD-16-0698,PMC6069599,,,"New data from Wang and colleagues show that complement C3 suppresses the function of CD8+ tumor-infiltrating T cells by inhibiting IL10 production, and targeting the complement receptors C3aR and C5aR enhances the antitumor activity of immune checkpoint blockade. Their results not only define a new role of complement receptors as T-cell coinhibitory receptors, but also are useful in the development of novel strategies to improve the effectiveness of cancer immunotherapy.",,"['Peng, W', 'McKenzie, JA', 'Hwu, P']",,,,
,PMC,The Emerging Role of RNA as a Therapeutic Target for Small Molecules,http://dx.doi.org/10.1016/j.chembiol.2016.05.021,PMC5064864,,,"Recent advances in understanding different RNAs and unique features of their biology have revealed a wealth of information. However, approaches to identify small molecules that target these newly discovered biological regulatory elements have been lacking. The application of new biochemical screening and design-based technologies, coupled with a resurgence of interest in phenotypic screening, has resulted in several compelling successes in targeting RNA. A number of recent advances suggest that achieving the longstanding goal of developing druglike, biologically active small molecules that target RNA is in fact possible. This review highlights advances and successes in approaches to targeting RNA with diverse small molecules, and the potential for these technologies to pave the way to new types of RNA-targeted therapeutics.",,"['Connelly, Colleen M.', 'Moon, Michelle H.', 'Schneekloth, John S.']",,,,
,PMC,Effect of Ventilated Caging on Water Intake and Loss in 4 Strains of Laboratory Mice,,PMC5029822,,,"Food availability, temperature, humidity, strain, and caging type all affect water consumption by mice. Measurement of transepidermal water loss (TEWL) is a new technique for the quantification of water turnover in mice. To understand water turnover in common strains of adult mice, male and female SCID, SKH, C57BL/6, and FVB mice were housed in same-sex groups of 5 animals in static cages or IVC. Body weight, TEWL, urine osmolality, and water consumption of mice and intracage temperature and humidity were measured every 48 h for comparison. Static cages were monitored for 7 d and IVC for 14 d before cage change. Female SCID, FVB, and C57 mice drank less water than did their male counterparts. Male and female SCID, SKH, and FVB mice in IVC drank less water and had higher urine osmolality than did those in static cages. In SCID and SKH mice, TEWL paralleled water consumption. C57 mice in static cages drank less water, had lower urine osmolality, and had less TEWL than did those in IVC. Temperature and humidity within the cage was higher than the macroenvironmental levels for all housing conditions, mouse strains, and sexes. Temperatures within IVC ranged from 76.6 to 81.4 °F compared with 69 ± 0.4 °F in the room. Humidity within IVC ranged from 68% to 79% compared with 27.o% ± 2.7% within the room. These data demonstrate that mouse strain and housing conditions significantly influence water balance and indicate that macroenvironmental measurements do not always reflect the intracage environment.",,"['Nicolaus, Mackenzie L', 'Bergdall, Valerie K', 'Davis, Ian C', 'Hickman-Davis, Judy M']",,,,
,PMC,Rapid Detection of Cyprinid Herpesvirus 3 in Latently Infected Koi (Cyprinus carpio) by Recombinase Polymerase Amplification,http://dx.doi.org/10.1080/08997659.2016.1185048,PMC5958048,,,"Since the emergence of cyprinid herpes virus 3 (CyHV-3), outbreaks have been devastating to koi and common carp leading to high economic losses. Current diagnostics for detecting CyHV-3 are limited in sensitivity and are further complicated by latency. Here we describe the detection of CyHV-3 by recombinase polymerase amplification (RPA). The RPA assay can detect as low as 10 copies of CyHV-3 genome by an isothermal reaction and yields results in approximately 20 minutes. Using the RPA assay, CyHV-3 genome can be detected in total DNA of white blood cells isolated from koi latently infected with CyHV-3, while less than 10% of the latently infected koi can be detected by a real-time PCR assay in total DNA of white blood cells. In addition, RPA products can be detected in a lateral flow device that is cheap, fast, and can be used outside of the diagnostic lab. The RPA assay and lateral flow device provide for the rapid, sensitive, and specific amplification of CyHV-3 that with future modifications for field use and validation could lead to enhanced surveillance and early diagnosis of CyHV-3 in the laboratory and field.",,"['Prescott, Meagan A.', 'Reed, Aimee N.', 'Jin, Ling', 'Pastey, Manoj K.']",,,,
,PMC,Liminal and invisible long-term care labour: Precarity in the face of austerity,http://dx.doi.org/10.1177/0022185616643496,PMC5102694,,,"Using feminist political economy, this article argues that companions hired privately by families to care for residents in publicly funded long-term care facilities (nursing homes) are a liminal and invisible labour force. A care gap, created by public sector austerity, has resulted in insufficient staff to meet residents’ health and social care needs. Families pay to fill this care gap in public funding with companion care, which limits demands on the state to collectively bear the costs of care for older adults. We assess companions’ work in light of Vosko’s (2015) and Rodgers and Rodgers’ (1989) dimensions for precariousness. We discuss how to classify paid care work that overlaps with paid formal and unpaid informal care. Our findings illuminate how companions’ labour is simultaneously autonomous and precarious; it fills a care gap and creates one, and can be relational compared with staffs’ task-oriented work.",,"['Daly, Tamara', 'Armstrong, Pat']",,,,
,PMC,Oral presentations,http://dx.doi.org/10.1177/1757177416663087,PMC5291341,,,,,,,,,
,PMC,"Narrowing of the Diagnostic Gap of Acute Gastroenteritis in Children 0-6 Years of Age Using a Combination of Classical and Molecular Techniques, Delivers Challenges in Syndromic Approach Diagnostics",http://dx.doi.org/10.1097/INF.0000000000001208,PMC4987234,,,"BACKGROUND: 25%-50% of acute gastroenteritis (AGE) cases remain etiologically undiagnosed. Our main aim was to determine the most appropriate list of enteric pathogens to be included in the daily diagnostics scheme of AGE, ensuring the lowest possible diagnostic gap. METHODS: 297 children ≤6 years of age, admitted to hospital in Slovenia, October 2011 – October 2012, with AGE, and 88 ≤6 year old healthy children, were included in the study. A broad spectrum of enteric pathogens was targeted with molecular methods, including 8 viruses, 6 bacteria and 2 parasites. RESULTS: At least one enteric pathogen was detected in 91.2% of cases with AGE and 27.3% of controls. Viruses were the most prevalent (82.5% and 15.9%), followed by bacteria (27.3% and 10.2%) and parasites (3.0% and 1.1%) in cases and controls, respectively. A high proportion (41.8%) of mixed infections was observed in the cases. For cases with undetermined etiology (8.8%), stool samples were analyzed with next generation sequencing and a potential viral pathogen was detected in 17 additional samples (5.8%). CONCLUSIONS: Our study suggests that tests for rotaviruses, noroviruses genogroup II, adenoviruses 40/41, astroviruses, Campylobacter spp. and Salmonella sp. should be included in the initial diagnostic algorithm, which revealed the etiology in 83.5% of children tested. The use of molecular methods in diagnostics of gastroenteritis is preferable because of their high sensitivity, specificity, fast performance and the possibility of establishing the concentration of the target. The latter may be valuable for assessing the clinical significance of the detected enteric, particularly viral pathogens.",,"['Steyer, Andrej', 'Jevšnik, Monika', 'Petrovec, Miroslav', 'Pokorn, Marko', 'Grosek, Štefan', 'Steyer, Adela Fratnik', 'Šoba, Barbara', 'Uršič, Tina', 'Kišek, Tjaša Cerar', 'Kolenc, Marko', 'Trkov, Marija', 'Šparl, Petra', 'Duraisamy, Raja', 'Lipkin, Ian W.', 'Terzić, Sara', 'Kolnik, Mojca', 'Mrvič, Tatjana', 'Kapoor, Amit', 'Strle, Franc']",,,,
,PMC,Autophagy Deficiency in Macrophages Enhances NLRP3 Inflammasome Activity and Chronic Lung Disease Following Silica Exposure,http://dx.doi.org/10.1016/j.taap.2016.08.029,PMC5054752,,,"Autophagy is an important metabolic mechanism that can promote cellular survival following injury. The specific contribution of autophagy to silica-induced inflammation and disease is not known. The objective of these studies was to determine the effects of silica exposure on the autophagic pathway in macrophages, as well as the general contribution of autophagy in macrophages to inflammation and disease. Silica exposure enhanced autophagic activity in vitro in Bone Marrow derived Macrophages and in vivo in Alveolar Macrophages isolated from silica-exposed mice. Impairment of autophagy in myeloid cells in vivo using Atg5(fl/fl)LysM-Cre(+) mice resulted in enhanced cytotoxicity and inflammation after silica exposure compared to littermate controls, including elevated IL-18 and the alarmin HMGB1 in the whole lavage fluid. Autophagy deficiency caused some spontaneous inflammation and disease. Greater silica-induced acute inflammation in Atg5(fl/fl)LysM-Cre(+) mice correlated with increased fibrosis and chronic lung disease. These studies demonstrate a critical role for autophagy in suppressing silica-induced cytotoxicity and inflammation in disease development. Furthermore, this data highlights the importance of basal autophagy in macrophages and other myeloid cells in maintaining lung homeostasis.",,"['Jessop, Forrest', 'Hamilton, Raymond F.', 'Rhoderick, Joseph F.', 'Shaw, Pamela K', 'Holian, Andrij']",,,,
,PMC,PNAS Plus Significance Statements,http://dx.doi.org/10.1073/pnas.ss11335,PMC5024616,,,,,,,,,
,PMC,In This Issue,http://dx.doi.org/10.1073/iti3516113,PMC5024606,,,,,,,,,
,PMC,Identification of small molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen,http://dx.doi.org/10.1038/nm.4184,PMC5386783,,,"In response to the current global health emergency posed by the Zika virus (ZIKV) outbreak and its link to microcephaly and other neurological conditions, we performed a drug repurposing screen of ~6,000 compounds that included approved drugs, clinical trial drug candidates and pharmacologically active compounds, and we identified compounds that either inhibit ZIKV infection or suppress infection-induced caspase-3 activity in different neural cells. A pan-caspase inhibitor, Emricasan, inhibited ZIKV-induced increases in caspase-3 activity and protected human cortical neural progenitors in both monolayer and 3-dimensional organoid cultures. Ten structurally unrelated inhibitors of cyclin-dependent kinases inhibited ZIKV replication. Niclosamide, an FDA approved category B anthelmintic drug, also inhibited ZIKV replication. Finally, combination treatments using one compound from each category (neuroprotective and antiviral) further increased protection of human neural progenitors and astrocytes from ZIKV-induced cell death. Our results demonstrate the efficacy of this screening strategy and identify lead compounds for anti-ZIKV drug development.",,"['Xu, Miao', 'Lee, Emily M.', 'Wen, Zhexing', 'Cheng, Yichen', 'Huang, Wei-Kai', 'Qian, Xuyu', 'TCW, Julia', 'Kouznetsova, Jennifer', 'Ogden, Sarah C.', 'Hammack, Christy', 'Jacob, Fadi', 'Nguyen, Ha Nam', 'Itkin, Misha', 'Hanna, Catherine', 'Shinn, Paul', 'Allen, Chase', 'Michael, Samuel G.', 'Simeonov, Anton', 'Huang, Wenwei', 'Christian, Kimberly M.', 'Goate, Alison', 'Brennand, Kristen J.', 'Huang, Ruili', 'Xia, Menghang', 'Ming, Guo-li', 'Zheng, Wei', 'Song, Hongjun', 'Tang, Hengli']",,,,
,PMC,Middle East respiratory syndrome (MERS): Emergence of a pathogenic human Coronavirus,http://dx.doi.org/10.1146/annurev-med-051215-031152,PMC5353356,,,"In 2012, a zoonotic coronavirus was identified as the causative agent of Middle East Respiratory Syndrome (MERS), called MERS Coronavirus (MERS-CoV). Since then, the virus has infected 1728 patients as of 12 May 2016, with a mortality rate of 36%. While MERS-CoV generally causes subclinical or mild disease, infection can result in serious outcomes, including acute respiratory distress syndrome (ARDS) and multi-organ failure in patients with co-morbidities. The virus is endemic in camels in the Arabian peninsula and Africa and thus poses a consistent threat of frequent reintroduction into human populations. Disease prevalence will increase substantially if the virus mutates to increase human-to-human transmissibility. No therapeutics or vaccines are approved for MERS; thus, development of novel therapies is needed. Further, since many MERS cases are acquired in healthcare settings, public health measures and scrupulous attention to infection control practices are required to prevent additional MERS outbreaks.",,"['Fehr, Anthony R.', 'Channapannavar, Rudragouda', 'Perlman, Stanley']",,,,
,PMC,Porcine Epidemic Diarrhea Virus Infection Inhibits Interferon Signaling by Targeted Degradation of STAT1,http://dx.doi.org/10.1128/JVI.01091-16,PMC5008104,,,"Porcine epidemic diarrhea virus (PEDV) is a worldwide-distributed alphacoronavirus, but the pathogenesis of PEDV infection is not fully characterized. During virus infection, type I interferon (IFN) is a key mediator of innate antiviral responses. Most coronaviruses develop some strategy for at least partially circumventing the IFN response by limiting the production of IFN and by delaying the activation of the IFN response. However, the molecular mechanisms by which PEDV antagonizes the antiviral effects of interferon have not been fully characterized. Especially, how PEDV impacts IFN signaling components has yet to be elucidated. In this study, we observed that PEDV was relatively resistant to treatment with type I IFN. Western blot analysis showed that STAT1 expression was markedly reduced in PEDV-infected cells and that this reduction was not due to inhibition of STAT1 transcription. STAT1 downregulation was blocked by a proteasome inhibitor but not by an autophagy inhibitor, strongly implicating the ubiquitin-proteasome targeting degradation system. Since PEDV infection-induced STAT1 degradation was evident in cells pretreated with the general tyrosine kinase inhibitor, we conclude that STAT1 degradation is independent of the IFN signaling pathway. Furthermore, we report that PEDV-induced STAT1 degradation inhibits IFN-α signal transduction pathways. Pharmacological inhibition of STAT1 degradation rescued the ability of the host to suppress virus replication. Collectively, these data show that PEDV is capable of subverting the type I interferon response by inducing STAT1 degradation. IMPORTANCE In this study, we show that PEDV is resistant to the antiviral effect of IFN. The molecular mechanism is the degradation of STAT1 by PEDV infection in a proteasome-dependent manner. This PEDV infection-induced STAT1 degradation contributes to PEDV replication. Our findings reveal a new mechanism evolved by PEDV to circumvent the host antiviral response.",,"['Guo, Longjun', 'Luo, Xiaolei', 'Li, Ren', 'Xu, Yunfei', 'Zhang, Jian', 'Ge, Jinying', 'Bu, Zhigao', 'Feng, Li', 'Wang, Yue']",,,,
,PMC,Biochemical and Structural Insights into the Preference of Nairoviral DeISGylases for Interferon-Stimulated Gene Product 15 Originating from Certain Species,http://dx.doi.org/10.1128/JVI.00975-16,PMC5008091,,,"The regulation of the interferon type I (IFN-I) response has been shown to rely on posttranslational modification by ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15) to stabilize, or activate, a variety of IFN-I signaling and downstream effector proteins. Unlike Ub, which is almost perfectly conserved among eukaryotes, ISG15 is highly divergent, even among mammals. Since zoonotic viruses rely on viral proteins to recognize, or cleave, ISG15 conjugates in order to evade, or suppress, innate immunity, the impact of ISG15 biodiversity on deISGylating proteases of the ovarian tumor family (vOTU) from nairoviruses was evaluated. The enzymatic activities of vOTUs originating from the Crimean-Congo hemorrhagic fever virus, Erve virus, and Nairobi sheep disease virus were tested against ISG15s from humans, mice, shrews, sheep, bats, and camels, which are mammalian species known to be infected by nairoviruses. This along with investigation of binding by isothermal titration calorimetry illustrated significant differences in the abilities of nairovirus deISGylases to accommodate certain species of ISG15. To investigate the molecular underpinnings of species preferences of these vOTUs, a structure was determined to 2.5 Å for a complex of Erve virus vOTU protease and a mouse ISG15 domain. This structure revealed the molecular basis of Erve virus vOTU's preference for ISG15 over Ub and the first structural insight into a nonhuman ISG15. This structure also revealed key interactions, or lack thereof, surrounding three amino acids that may drive a viral deISgylase to prefer an ISG15 from one species over that of another. IMPORTANCE Viral ovarian tumor domain proteases (vOTUs) are one of the two principal classes of viral proteases observed to reverse posttranslational modification of host proteins by ubiquitin and interferon-stimulated gene product 15 (ISG15), subsequently facilitating downregulation of IFN-I signaling pathways. Unlike the case with ubiquitin, the amino acid sequences of ISG15s from various species are notably divergent. We illustrate that vOTUs have clear preferences for ISG15s from certain species. In addition, these observations are related to the molecular insights acquired via the first X-ray structure of the vOTU from the Erve nairovirus in complex with the first structurally resolved nonhuman ISG15. This information implicates certain amino acids that drive the preference of vOTUs for ISG15s from certain species.",,"['Deaton, M. K.', 'Dzimianski, J. V.', 'Daczkowski, C. M.', 'Whitney, G. K.', 'Mank, N. J.', 'Parham, M. M.', 'Bergeron, E.', 'Pegan, S. D.']",,,,
,PMC,The Interferon-Stimulated Gene Ifitm3 Restricts West Nile Virus Infection and Pathogenesis,http://dx.doi.org/10.1128/JVI.00581-16,PMC5008082,,,"The interferon-induced transmembrane protein (IFITM) family of proteins inhibit infection of several different enveloped viruses in cell culture by virtue of their ability to restrict entry and fusion from late endosomes. As few studies have evaluated the importance of Ifitm3 in vivo in restricting viral pathogenesis, we investigated its significance as an antiviral gene against West Nile virus (WNV), an encephalitic flavivirus, in cells and mice. Ifitm3(−/−) mice were more vulnerable to lethal WNV infection, and this was associated with greater virus accumulation in peripheral organs and central nervous system tissues. As no difference in viral burden in the brain or spinal cord was observed after direct intracranial inoculation, Ifitm3 likely functions as an antiviral protein in nonneuronal cells. Consistent with this, Ifitm3(−/−) fibroblasts but not dendritic cells resulted in higher yields of WNV in multistep growth analyses. Moreover, transcomplementation experiments showed that Ifitm3 inhibited WNV infection independently of Ifitm1, Ifitm2, Ifitm5, and Ifitm6. Beyond a direct effect on viral infection in cells, analysis of the immune response in WNV-infected Ifitm3(−/−) mice showed decreases in the total number of B cells, CD4(+) T cells, and antigen-specific CD8(+) T cells. Finally, bone marrow chimera experiments demonstrated that Ifitm3 functioned in both radioresistant and radiosensitive cells, as higher levels of WNV were observed in the brain only when Ifitm3 was absent from both compartments. Our analyses suggest that Ifitm3 restricts WNV pathogenesis likely through multiple mechanisms, including the direct control of infection in subsets of cells. IMPORTANCE As part of the mammalian host response to viral infections, hundreds of interferon-stimulated genes (ISGs) are induced. The inhibitory activity of individual ISGs varies depending on the specific cell type and viral pathogen. Among ISGs, the genes encoding interferon-induced transmembrane protein (IFITM) have been reported to inhibit multiple families of viruses in cell culture. However, few reports have evaluated the impact of IFITM genes on viral pathogenesis in vivo. In this study, we characterized the antiviral activity of Ifitm3 against West Nile virus (WNV), an encephalitic flavivirus, using mice with a targeted gene deletion of Ifitm3. Based on extensive virological and immunological analyses, we determined that Ifitm3 protects mice from WNV-induced mortality by restricting virus accumulation in peripheral organs and, subsequently, in central nervous system tissues. Our data suggest that Ifitm3 restricts WNV pathogenesis by multiple mechanisms and functions in part by controlling infection in different cell types.",,"['Gorman, Matthew J.', 'Poddar, Subhajit', 'Farzan, Michael', 'Diamond, Michael S.']",,,,
,PMC,Desmosterol increases lipid bilayer fluidity during hepatitis C virus infection,http://dx.doi.org/10.1021/acsinfecdis.6b00086,PMC5161114,,,"Hepatitis C virus (HCV) uniquely affects desmosterol homeostasis by increasing its intracellular abundance and affecting its localization. These effects are important for productive viral replication since inhibition of desmosterol synthesis has an antiviral effect that can be rescued by the addition of exogenous desmosterol. Here, we use subgenomic replicons to show that desmosterol has a major effect on replication of HCV JFH1 RNA. Fluorescence recovery after photobleaching (FRAP) experiments performed with synthetic supported lipid bilayers demonstrate that substitution of desmosterol for cholesterol significantly increases lipid bilayer fluidity, especially in the presence of saturated phospholipids and ceramides. We demonstrate using LC-MS that desmosterol is abundant in the membranes upon which genome replication takes place and that supported lipid bilayers derived from these specialized membranes also exhibit significantly higher fluidity compared to negative control membranes isolated from cells lacking HCV. Together, these data suggest a model in which the fluidity-promoting effects of desmosterol on lipid bilayers play a crucial role in the extensive membrane remodeling that takes place in the endoplasmic reticulum during HCV infection. We anticipate that the supported lipid bilayer system described can provide a useful model system in which to interrogate the effects of lipid structure and composition on the biophysical properties of lipid membranes as well as their function in viral processes such as genome replication.",,"['Costello, Deirdre A.', 'Villareal, Valerie A.', 'Yang, Priscilla L.']",,,,
,PMC,"Structure, Function, and Evolution of Coronavirus Spike Proteins",http://dx.doi.org/10.1146/annurev-virology-110615-042301,PMC5457962,,,"The coronavirus spike protein is a multifunctional molecular machine that mediates coronavirus entry into host cells. It first binds to a receptor on the host cell surface through its S1 subunit and then fuses viral and host membranes through its S2 subunit. Two domains in S1 from different coronaviruses recognize a variety of host receptors, leading to viral attachment. The spike protein exists in two structurally distinct conformations, prefusion and postfusion. The transition from prefusion to postfusion conformation of the spike protein must be triggered, leading to membrane fusion. This article reviews current knowledge about the structures and functions of coronavirus spike proteins, illustrating how the two S1 domains recognize different receptors and how the spike proteins are regulated to undergo conformational transitions. I further discuss the evolution of these two critical functions of coronavirus spike proteins, receptor recognition and membrane fusion, in the context of the corresponding functions from other viruses and host cells.",,"Li, Fang",,,,
,PMC,Is hand hygiene frequency associated with the onset of outbreaks in pediatric long-term care?,http://dx.doi.org/10.1016/j.ajic.2016.06.022,PMC5135613,,,"BACKGROUND: Studies in adult long-term care facilities (LTCFs) have shown a correlation between hand hygiene (HH) and viral outbreak reduction, but no such studies have been conducted in pediatric LTCFs where the epidemiology of viral pathogens is different. METHODS: We compared electronically monitored facility-wide HH frequency in the weeks immediately prior to outbreaks of acute respiratory or gastrointestinal infections versus control weeks in a 137-bed pediatric LTCF from October 2012-August 2015. Control weeks were the 8-14 day (control 1) and 15-21 day (control 2) periods prior to the onset of each outbreak. RESULTS: There was no difference in HH frequency in the weeks leading up to the outbreaks versus control weeks (odds ratio [OR], 1.0; 95% confidence interval CI, 1.00-1.001 using control 1 and OR, 1.0; 95% CI, 1.00-1.001 using control 2). CONCLUSIONS: Our findings differed from those in adult LTFCs, possibly because of the greater contact between residents and staff in the pediatric setting, increased susceptibility to viral pathogens because of immunologic immaturity, or differences in the types of pathogens prevalent in each setting. Although HH may be important for limiting the number of residents infected during outbreaks, we found no association between HH frequency and subsequent outbreak onset.",,"['Cohen, Bevin', 'Murray, Meghan', 'Jia, Haomiao', 'Jackson, Olivia', 'Saiman, Lisa', 'Neu, Natalie', 'Hutcheon, Gordon', 'Larson, Elaine']",,,,
,PMC,Safe and Sensitive Antiviral Screening Platform Based on Recombinant Human Coronavirus OC43 Expressing the Luciferase Reporter Gene,http://dx.doi.org/10.1128/AAC.00814-16,PMC4997878,,,"Human coronaviruses (HCoVs) cause 15 to 30% of mild upper respiratory tract infections. However, no specific antiviral drugs are available to prevent or treat HCoV infections to date. Here, we developed four infectious recombinant HCoVs-OC43 (rHCoVs-OC43) which express the Renilla luciferase (Rluc) reporter gene. Among these four rHCoVs-OC43, rOC43-ns2DelRluc (generated by replacing ns2 with the Rluc gene) showed robust luciferase activity with only a slight impact on its growth characteristics. Additionally, this recombinant virus remained stable for at least 10 passages in BHK-21 cells. rOC43-ns2DelRluc was comparable to its parental wild-type virus (HCoV-OC43-WT) with respect to the quantity of the antiviral activity of chloroquine and ribavirin. We showed that chloroquine strongly inhibited HCoV-OC43 replication in vitro, with a 50% inhibitory concentration (IC(50)) of 0.33 μM. However, ribavirin showed inhibition of HCoV-OC43 replication only at high concentrations which may not be applicable to humans in clinical treatment, with an IC(50) of 10 μM. Furthermore, using a luciferase-based small interfering RNA (siRNA) screening assay, we identified double-stranded-RNA-activated protein kinase (PKR) and DEAD box RNA helicases (DDX3X) that exhibited antiviral activities, which were further verified by the use of HCoV-OC43-WT. Therefore, rOC43-ns2DelRluc represents a promising safe and sensitive platform for high-throughput antiviral screening and quantitative analysis of viral replication.",,"['Shen, Liang', 'Yang, Yang', 'Ye, Fei', 'Liu, Gaoshan', 'Desforges, Marc', 'Talbot, Pierre J.', 'Tan, Wenjie']",,,,
,PMC,Effective one-pot multienzyme (OPME) synthesis of monotreme milk oligosaccharides and other sialosides containing a 4-O-acetyl sialic acid(),http://dx.doi.org/10.1039/c6ob01706a,PMC5036589,,,"A facile one-pot two-enzyme chemoenzymatic approach has been established for gram (Neu4,5Ac(2)α3Lac, 1.33 g) and preparative-scale (Neu4,5Ac(2)α3LNnT) synthesis of monotreme milk oligosaccharides. Other O-acetyl-5-N-acetylneuraminic acid (Neu4,5Ac(2))- or 4-O-acetyl-5-N-glycolylneuraminic acid (Neu4Ac5Gc)-containing α2–3-sialosides have also been synthesized in preparative scale. Used as an effective probe, Neu4,5Ac(2)α3GalβpNP was found to be a suitable substrate by human influenza A viruses but not bacterial sialidases.",,"['Yu, Hai', 'Zeng, Jie', 'Li, Yanhong', 'Thon, Vireak', 'Shi, Baojun', 'Chen, Xi']",,,,
,PMC,"Communication Between Infectious Disease Physicians and US State and Local Public Health Agencies: Strengths, Challenges, and Opportunities",http://dx.doi.org/10.1177/0033354916660083,PMC5230817,,,"Strong working relationships between infectious disease (ID) physicians and public health have resulted in the early detection of emerging infectious threats. From May 6 through June 5, 2015, we surveyed ID physicians in the Infectious Diseases Society of America’s Emerging Infections Network about communications with public health. A total of 688 of 1491 (46%) members completed the survey, 624 (91%) of whom knew how to reach their health department directly for an urgent issue. Only 38 (6%) described communications with their health department as poor. Interest in newer technologies (eg, mobile smartphone applications) showed mixed results. Interest in a smartphone application differed significantly by years of ID experience, with 81 of 146 (55%) respondents with <5 years of ID experience, 172 of 359 (48%) respondents with 5 to 24 years of ID experience, and 61 of 183 (33%) respondents with ≥25 years of ID experience in favor of a smartphone application (P < .001). As more physicians adopt newer communication technologies, health departments should be prepared to incorporate these tools to communicate with ID physicians.",,"['Santibañez, Scott', 'Polgreen, Philip M.', 'Beekmann, Susan E.', 'Cairns, Catherine', 'Filice, Gregory A.', 'Layton, Marcelle', 'Hughes, James M.']",,,,
,PMC,"Identifying and Addressing the Daily Needs of Contacts of an Ebola Patient During Investigation, Monitoring, and Movement Restriction, Ohio",http://dx.doi.org/10.1177/0033354916660087,PMC5230816,,,,,"['McCarty, Carolyn L.', 'Karwowski, Mateusz P.', 'Basler, Colin', 'Erme, Marguerite', 'Kippes, Chris', 'Quinn, Kim', 'de Fijter, Sietske', 'DiOrio, Mary', 'Braden, Christopher', 'Knust, Barbara', 'Santibañez, Scott']",,,,
,PMC,Resolution advances in cryo-EM enable application to drug discovery,http://dx.doi.org/10.1016/j.sbi.2016.07.009,PMC5154827,,,"The prospect that the structures of protein assemblies, small and large, can be determined using cryo-electron microscopy (cryo-EM) is beginning to transform the landscape of structural biology and cell biology. Great progress is being made in determining 3D structures of biological assemblies ranging from icosahedral viruses and helical arrays to small membrane proteins and protein complexes. Here, we review recent advances in this field, focusing especially on the emerging use of cryo-EM in mapping the binding of drugs and inhibitors to protein targets, an application that requires structure determination at the highest possible resolutions. We discuss methods used to evaluate the information contained in cryo-EM density maps and consider strengths and weaknesses of approaches currently used to measure map resolution.",,"['Subramaniam, Sriram', 'Earl, Lesley A.', 'Falconieri, Veronica', 'Milne, Jacqueline L. S.', 'Egelman, Edward H.']",,,,
,PMC,Viral bronchiolitis,http://dx.doi.org/10.1016/S0140-6736(16)30951-5,PMC6765220,,,"Viral bronchiolitis is a common clinical syndrome affecting infants and young children. Concern about its associated morbidity and cost has led to a large body of research that has been summarised in systematic reviews and integrated into clinical practice guidelines in several countries. The evidence and guideline recommendations consistently support a clinical diagnosis with the limited role for diagnostic testing for children presenting with the typical clinical syndrome of viral upper respiratory infection progressing to the lower respiratory tract. Management is largely supportive, focusing on maintaining oxygenation and hydration of the patient. Evidence suggests no benefit from bronchodilator or corticosteroid use in infants with a first episode of bronchiolitis. Evidence for other treatments such as hypertonic saline is evolving but not clearly defined yet. For infants with severe disease, the insufficient available data suggest a role for high-flow nasal cannula and continuous positive airway pressure use in a monitored setting to prevent respiratory failure.",,"['Florin, Todd A', 'Plint, Amy C', 'Zorc, Joseph J']",,,,
,PMC,Journal Watch,http://dx.doi.org/10.1177/1757177416659535,PMC5102082,,,,,"['Wigglesworth, Neil', 'Xuereb, Deborah']",,,,
,PMC,Highlighting the need for more infection control practitioners in low- and middle-income countries,http://dx.doi.org/10.5588/pha.16.0027,PMC5034780,,,"Background: Many low- and middle-income countries struggle to implement, monitor and evaluate the efficacy of infection control (IC) measures within health care facilities. This hampers their ability to prevent nosocomial infections, identify emerging pathogens and rapidly alert officials to possible outbreaks. The lack of dedicated and trained IC practitioners (ICPs) is a serious deficit in the health care workforce, and is worsened by the lack of institutions that offer IC training. Discussion: While no single individual can entirely eliminate the risk of nosocomial transmission, there is literature to support the value of designated IC persons. Recommendations from the World Health Organization in 2008 and 2009 describe the need for this specialized cadre of workers, but many countries lack the national regulations to authorize, train and manage such professionals at the national or local level. This article provides an overview of how ICPs are trained and credentialed in several countries, and discusses approaches countries can use to train ICPs. Conclusion: Trained ICPs can help prevent future outbreaks and control nosocomial transmission of diseases in health care facilities. For this to occur, supportive national policies, availability of training institutions and local administrative support will be required.",,"['Lipke, V.', 'Emerson, C.', 'McCarthy, C.', 'Briggs-Hagen, M.', 'Farley, J.', 'Verani, A. R.', 'Riley, P. L.']",,,,
,PMC,Spautin-1 Ameliorates Acute Pancreatitis via Inhibiting Impaired Autophagy and Alleviating Calcium Overload,http://dx.doi.org/10.2119/molmed.2016.00034,PMC5082290,,,"Acute pancreatitis is characterized by zymogen preactivation. Severe inflammation caused by zymogen activation can eventually lead to multiple organ dysfunctions which contribute to the high mortality rate of severe acute pancreatitis. However, there is no specific treatment available for acute pancreatitis therapy. Here, we show that spautin-1, which effectively inhibits autophagy flux, ameliorated the pathogenesis of acute pancreatitis induced by cerulein or L-arginine. CaMKII phosphorylation due to cytosolic calcium overload was revealed in this paper. It was also demonstrated that autophagic protein aggregates degradation blockade accompanied by impaired autophagy correlated positively with intra-acinar cell digestive aymogen activation stimulated by cerulein or L-arginine. The role of spautin-1 in ameliorating acute pancreatitis was shown here to be associated with impaired autophagy inhibition and Ca(2+) overload alleviation. We provide a promising therapy for acute pancreatitis through targeting both impaired autophagy and increased cytosolic calcium.",,"['Xiao, Juan', 'Feng, Xueping', 'Huang, Xiao-Ying', 'Huang, Zhongshi', 'Huang, Yanqiang', 'Li, Chaogan', 'Li, Genliang', 'Nong, Song', 'Wu, Ruoshi', 'Huang, Yongzhi', 'Long, Xi-Dai']",,,,
,PMC,Unbiased identification of signal-activated transcription factors by barcoded synthetic tandem repeat promoter screening (BC-STAR-PROM),http://dx.doi.org/10.1101/gad.284828.116,PMC5024686,,,"The discovery of transcription factors (TFs) controlling pathways in health and disease is of paramount interest. We designed a widely applicable method, dubbed barcorded synthetic tandem repeat promoter screening (BC-STAR-PROM), to identify signal-activated TFs without any a priori knowledge about their properties. The BC-STAR-PROM library consists of ∼3000 luciferase expression vectors, each harboring a promoter (composed of six tandem repeats of synthetic random DNA) and an associated barcode of 20 base pairs (bp) within the 3′ untranslated mRNA region. Together, the promoter sequences encompass >400,000 bp of random DNA, a sequence complexity sufficient to capture most TFs. Cells transfected with the library are exposed to a signal, and the mRNAs that it encodes are counted by next-generation sequencing of the barcodes. This allows the simultaneous activity tracking of each of the ∼3000 synthetic promoters in a single experiment. Here we establish proof of concept for BC-STAR-PROM by applying it to the identification of TFs induced by drugs affecting actin and tubulin cytoskeleton dynamics. BC-STAR-PROM revealed that serum response factor (SRF) is the only immediate early TF induced by both actin polymerization and microtubule depolymerization. Such changes in cytoskeleton dynamics are known to occur during the cell division cycle, and real-time bioluminescence microscopy indeed revealed cell-autonomous SRF–myocardin-related TF (MRTF) activity bouts in proliferating cells.",,"['Gosselin, Pauline', 'Rando, Gianpaolo', 'Fleury-Olela, Fabienne', 'Schibler, Ueli']",,,,
,PMC,Link of a ubiquitous human coronavirus to dromedary camels,http://dx.doi.org/10.1073/pnas.1604472113,PMC5024591,,,"The four human coronaviruses (HCoVs) are globally endemic respiratory pathogens. The Middle East respiratory syndrome (MERS) coronavirus (CoV) is an emerging CoV with a known zoonotic source in dromedary camels. Little is known about the origins of endemic HCoVs. Studying these viruses’ evolutionary history could provide important insight into CoV emergence. In tests of MERS-CoV–infected dromedaries, we found viruses related to an HCoV, known as HCoV-229E, in 5.6% of 1,033 animals. Human- and dromedary-derived viruses are each monophyletic, suggesting ecological isolation. One gene of dromedary viruses exists in two versions in camels, full length and deleted, whereas only the deleted version exists in humans. The deletion increased in size over a succession starting from camelid viruses via old human viruses to contemporary human viruses. Live isolates of dromedary 229E viruses were obtained and studied to assess human infection risks. The viruses used the human entry receptor aminopeptidase N and replicated in human hepatoma cells, suggesting a principal ability to cause human infections. However, inefficient replication in several mucosa-derived cell lines and airway epithelial cultures suggested lack of adaptation to the human host. Dromedary viruses were as sensitive to the human type I interferon response as HCoV-229E. Antibodies in human sera neutralized dromedary-derived viruses, suggesting population immunity against dromedary viruses. Although no current epidemic risk seems to emanate from these viruses, evolutionary inference suggests that the endemic human virus HCoV-229E may constitute a descendant of camelid-associated viruses. HCoV-229E evolution provides a scenario for MERS-CoV emergence.",,"['Corman, Victor M.', 'Eckerle, Isabella', 'Memish, Ziad A.', 'Liljander, Anne M.', 'Dijkman, Ronald', 'Jonsdottir, Hulda', 'Juma Ngeiywa, Kisi J. Z.', 'Kamau, Esther', 'Younan, Mario', 'Al Masri, Malakita', 'Assiri, Abdullah', 'Gluecks, Ilona', 'Musa, Bakri E.', 'Meyer, Benjamin', 'Müller, Marcel A.', 'Hilali, Mosaad', 'Bornstein, Set', 'Wernery, Ulrich', 'Thiel, Volker', 'Jores, Joerg', 'Drexler, Jan Felix', 'Drosten, Christian']",,,,
,PMC,Mapping of Ebolavirus Neutralization by Monoclonal Antibodies in the ZMapp Cocktail Using Cryo-Electron Tomography and Studies of Cellular Entry,http://dx.doi.org/10.1128/JVI.00406-16,PMC4988163,,,"ZMapp, a cocktail of three monoclonal antibodies (MAbs; c2G4, c4G7, and c13C6) against the ebolavirus (EBOV) glycoprotein (GP), shows promise for combatting outbreaks of EBOV, as occurred in West Africa in 2014. Prior studies showed that Fabs from these MAbs bind a soluble EBOV GP ectodomain and that MAbs c2G4 and c4G7, but not c13C6, neutralize infections in cell cultures. Using cryo-electron tomography, we extended these findings by characterizing the structures of c2G4, c4G7, and c13C6 IgGs bound to native, full-length GP from the West African 2014 isolate embedded in filamentous viruslike particles (VLPs). As with the isolated ectodomain, c13C6 bound to the glycan cap, whereas c2G4 and c4G7 bound to the base region of membrane-bound GP. The tomographic data suggest that all three MAbs bind with high occupancy and that the base-binding antibodies can potentially bridge neighboring GP spikes. Functional studies indicated that c2G4 and c4G7, but not c13C6, competitively inhibit entry of VLPs bearing EBOV GP into the host cell cytoplasm, without blocking trafficking of VLPs to NPC1(+) endolysosomes, where EBOV fuses. Moreover, c2G4 and c4G7 bind to and can block entry mediated by the primed (19-kDa) form of GP without impeding binding of the C-loop of NPC1, the endolysosomal receptor for EBOV. The most likely mode of action of c2G4 and c4G7 is therefore by inhibiting conformational changes in primed, NPC1-bound GP that initiate fusion between the viral and target membranes, similar to the action of certain broadly neutralizing antibodies against influenza hemagglutinin and HIV Env. IMPORTANCE The recent West African outbreak of ebolavirus caused the deaths of more than 11,000 individuals. Hence, there is an urgent need to be prepared with vaccines and therapeutics for similar future disasters. ZMapp, a cocktail of three MAbs directed against the ebolavirus glycoprotein, is a promising anti-ebolavirus therapeutic. Using cryo-electron tomography, we provide structural information on how each of the MAbs in this cocktail binds to the ebolavirus glycoprotein as it is displayed—embedded in the membrane and present at high density—on filamentous viruslike particles that recapitulate the surface structure and entry functions of ebolavirus. Moreover, after confirming that two of the MAbs bind to the same region in the base of the glycoprotein, we show that they competitively block the entry function of the glycoprotein and that they can do so after the glycoprotein is proteolytically primed and bound to its intracellular receptor, Niemann-Pick C1. These findings should inform future developments of ebolavirus therapeutics.",,"['Tran, Erin E. H.', 'Nelson, Elizabeth A.', 'Bonagiri, Pranay', 'Simmons, James A.', 'Shoemaker, Charles J.', 'Schmaljohn, Connie S.', 'Kobinger, Gary P.', 'Zeitlin, Larry', 'Subramaniam, Sriram', 'White, Judith M.']",,,,
,PMC,Opposing Roles of Double-Stranded RNA Effector Pathways and Viral Defense Proteins Revealed with CRISPR-Cas9 Knockout Cell Lines and Vaccinia Virus Mutants,http://dx.doi.org/10.1128/JVI.00869-16,PMC4988158,,,"Vaccinia virus (VACV) decapping enzymes and cellular exoribonuclease Xrn1 catalyze successive steps in mRNA degradation and prevent double-stranded RNA (dsRNA) accumulation, whereas the viral E3 protein can bind dsRNA. We showed that dsRNA and E3 colocalized within cytoplasmic viral factories in cells infected with a decapping enzyme mutant as well as with wild-type VACV and that they coprecipitated with antibody. An E3 deletion mutant induced protein kinase R (PKR) and eukaryotic translation initiation factor alpha (eIF2α) phosphorylation earlier and more strongly than a decapping enzyme mutant even though less dsRNA was made, leading to more profound effects on viral gene expression. Human HAP1 and A549 cells were genetically modified by clustered regularly interspaced short palindromic repeat-Cas9 (CRISPR-Cas9) to determine whether the same pathways restrict E3 and decapping mutants. The E3 mutant replicated in PKR knockout (KO) HAP1 cells in which RNase L is intrinsically inactive but only with a double knockout (DKO) of PKR and RNase L in A549 cells, indicating that both pathways decreased replication equivalently and that no additional dsRNA pathway was crucial. In contrast, replication of the decapping enzyme mutant increased significantly (though less than that of wild-type virus) in DKO A549 cells but not in DKO HAP1 cells where a smaller increase in viral protein synthesis occurred. Xrn1 KO A549 cells were viable but nonpermissive for VACV; however, wild-type and mutant viruses replicated in triple-KO cells in which RNase L and PKR were also inactivated. Since KO of PKR and RNase L was sufficient to enable VACV replication in the absence of E3 or Xrn1, the poor replication of the decapping mutant, particularly in HAP1 DKO, cells indicated additional translational defects. IMPORTANCE Viruses have evolved ways of preventing or counteracting the cascade of antiviral responses that double-stranded RNA (dsRNA) triggers in host cells. We showed that the dsRNA produced in excess in cells infected with a vaccinia virus (VACV) decapping enzyme mutant and by wild-type virus colocalized with the viral E3 protein in cytoplasmic viral factories. Novel human cell lines defective in either or both protein kinase R and RNase L dsRNA effector pathways and/or the cellular 5′ exonuclease Xrn1 were prepared by CRISPR-Cas9 gene editing. Inactivation of both pathways was necessary and sufficient to allow full replication of the E3 mutant and reverse the defect cause by inactivation of Xrn1, whereas the decapping enzyme mutant still exhibited defects in gene expression. The study provided new insights into functions of the VACV proteins, and the well-characterized panel of CRISPR-Cas9-modified human cell lines should have broad applicability for studying innate dsRNA pathways.",,"['Liu, Ruikang', 'Moss, Bernard']",,,,
,PMC,DC-SIGN and L-SIGN Are Attachment Factors That Promote Infection of Target Cells by Human Metapneumovirus in the Presence or Absence of Cellular Glycosaminoglycans,http://dx.doi.org/10.1128/JVI.00537-16,PMC4988148,,,"It is well established that glycosaminoglycans (GAGs) function as attachment factors for human metapneumovirus (HMPV), concentrating virions at the cell surface to promote interaction with other receptors for virus entry and infection. There is increasing evidence to suggest that multiple receptors may exhibit the capacity to promote infectious entry of HMPV into host cells; however, definitive identification of specific transmembrane receptors for HMPV attachment and entry is complicated by the widespread expression of cell surface GAGs. pgsA745 Chinese hamster ovary (CHO) cells are deficient in the expression of cell surface GAGs and resistant to HMPV infection. Here, we demonstrate that the expression of the Ca(2+)-dependent C-type lectin receptor (CLR) DC-SIGN (CD209L) or L-SIGN (CD209L) rendered pgsA745 cells permissive to HMPV infection. Unlike infection of parental CHO cells, HMPV infection of pgsA745 cells expressing DC-SIGN or L-SIGN was dynamin dependent and inhibited by mannan but not by pretreatment with bacterial heparinase. Parental CHO cells expressing DC-SIGN/L-SIGN also showed enhanced susceptibility to dynamin-dependent HMPV infection, confirming that CLRs can promote HMPV infection in the presence or absence of GAGs. Comparison of pgsA745 cells expressing wild-type and endocytosis-defective mutants of DC-SIGN/L-SIGN indicated that the endocytic function of CLRs was not essential but could contribute to HMPV infection of GAG-deficient cells. Together, these studies confirm a role for CLRs as attachment factors and entry receptors for HMPV infection. Moreover, they define an experimental system that can be exploited to identify transmembrane receptors and entry pathways where permissivity to HMPV infection can be rescued following the expression of a single cell surface receptor. IMPORTANCE On the surface of CHO cells, glycosaminoglycans (GAGs) function as the major attachment factor for human metapneumoviruses (HMPV), promoting dynamin-independent infection. Consistent with this, GAG-deficient pgaA745 CHO cells are resistant to HMPV. However, expression of DC-SIGN or L-SIGN rendered pgsA745 cells permissive to dynamin-dependent infection by HMPV, although the endocytic function of DC-SIGN/L-SIGN was not essential for, but could contribute to, enhanced infection. These studies provide direct evidence implicating DC-SIGN/L-SIGN as an alternate attachment factor for HMPV attachment, promoting dynamin-dependent infection via other unknown receptors in the absence of GAGs. Moreover, we describe a unique experimental system for the assessment of putative attachment and entry receptors for HMPV.",,"['Gillespie, Leah', 'Gerstenberg, Kathleen', 'Ana-Sosa-Batiz, Fernanda', 'Parsons, Matthew S.', 'Farrukee, Rubaiyea', 'Krabbe, Mark', 'Spann, Kirsten', 'Brooks, Andrew G.', 'Londrigan, Sarah L.', 'Reading, Patrick C.']",,,,
,PMC,Tools for Model Building and Optimization into Near-Atomic Resolution Electron Cryo-Microscopy Density Maps,http://dx.doi.org/10.1016/bs.mie.2016.06.003,PMC5103630,,,"Electron cryo-microscopy (cryoEM) has advanced dramatically to become a viable tool for high-resolution structural biology research. The ultimate outcome of a cryoEM study is an atomic model of a macromolecule or its complex with interacting partners. This chapter describes a variety of algorithms and software to build a de novo model based on the cryoEM 3D density map, to optimize the model with the best stereochemistry restraints and finally to validate the model with proper protocols. The full process of atomic structure determination from a cryoEM map is described. The tools outlined in this chapter should prove extremely valuable in revealing atomic interactions guided by cryoEM data.",,"['DiMaio, F.', 'Chiu, W.']",,,,
,PMC,p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PL(pro) via E3 ubiquitin ligase RCHY1,http://dx.doi.org/10.1073/pnas.1603435113,PMC5024628,,,"Highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) has developed strategies to inhibit host immune recognition. We identify cellular E3 ubiquitin ligase ring-finger and CHY zinc-finger domain-containing 1 (RCHY1) as an interacting partner of the viral SARS-unique domain (SUD) and papain-like protease (PL(pro)), and, as a consequence, the involvement of cellular p53 as antagonist of coronaviral replication. Residues 95–144 of RCHY1 and 389–652 of SUD (SUD-NM) subdomains are crucial for interaction. Association with SUD increases the stability of RCHY1 and augments RCHY1-mediated ubiquitination as well as degradation of p53. The calcium/calmodulin-dependent protein kinase II delta (CAMK2D), which normally influences RCHY1 stability by phosphorylation, also binds to SUD. In vivo phosphorylation shows that SUD does not regulate phosphorylation of RCHY1 via CAMK2D. Similarly to SUD, the PL(pro)s from SARS-CoV, MERS-CoV, and HCoV-NL63 physically interact with and stabilize RCHY1, and thus trigger degradation of endogenous p53. The SARS-CoV papain-like protease is encoded next to SUD within nonstructural protein 3. A SUD–PL(pro) fusion interacts with RCHY1 more intensively and causes stronger p53 degradation than SARS-CoV PL(pro) alone. We show that p53 inhibits replication of infectious SARS-CoV as well as of replicons and human coronavirus NL63. Hence, human coronaviruses antagonize the viral inhibitor p53 via stabilizing RCHY1 and promoting RCHY1-mediated p53 degradation. SUD functions as an enhancer to strengthen interaction between RCHY1 and nonstructural protein 3, leading to a further increase in in p53 degradation. The significance of these findings is that down-regulation of p53 as a major player in antiviral innate immunity provides a long-sought explanation for delayed activities of respective genes.",,"['Ma-Lauer, Yue', 'Carbajo-Lozoya, Javier', 'Hein, Marco Y.', 'Müller, Marcel A.', 'Deng, Wen', 'Lei, Jian', 'Meyer, Benjamin', 'Kusov, Yuri', 'von Brunn, Brigitte', 'Bairad, Dev Raj', 'Hünten, Sabine', 'Drosten, Christian', 'Hermeking, Heiko', 'Leonhardt, Heinrich', 'Mann, Matthias', 'Hilgenfeld, Rolf', 'von Brunn, Albrecht']",,,,
,PMC,Genotyping and pathotyping of diversified strains of infectious bronchitis viruses circulating in Egypt,http://dx.doi.org/10.5501/wjv.v5.i3.125,PMC4981825,,,"AIM: To characterize the circulating infectious bronchitis virus (IBV) strains in Egypt depending on the sequence of the spike-1 (S1) gene [hypervariable region-3 (HVR-3)] and to study the pathotypic features of these strains. METHODS: In this work, twenty flocks were sampled for IBV detection using RRT-PCR and isolation of IBV in specific pathogen free (SPF) chicks during the period from 2010 to 2015. Partial sequencing and phylogenetic analysis of 400 bp representing the HVR-3 of the S1 gene was conducted. Pathotypic characterization of one selected virus from each group (Egy/Var-I, Egy/Var-II and classic) was evaluated in one day old SPF chicks. The chicks were divided into 4 groups 10 birds each including the negative control group. Birds were inoculated at one day by intranasal instillation of 10(5)EID(50)/100 μL of IBV viruses [IBV-EG/1212B-2012 (Egy/Var-II), IBV/EG/IBV1-2011 (Egy/Var-I) and IBV-EG/11539F-2011 (classic)], while the remaining negative control group was kept uninfected. The birds were observed for clinical signs, gross lesions and virus pathogenicity. The real-time rRT-PCR test was performed for virus detection in the tissues. Histopathological examinations were evaluated in both trachea and kidneys. RESULTS: The results revealed that these viruses were separated into two distinct groups; variant (GI-23) and classic (GI-1), where 16 viruses belonged to a variant group, including 2 subdivisions [Egy/Var-I (6 isolates) and Egy/Var-II (10 isolates)] and 4 viruses clustered to the classic group (Mass-like). IBV isolates in the variant group were grouped with other IBV strains from the Middle East. The variant subgroup (Egy/Var-I) was likely resembling the original Egyptian variant strain (Egypt/Beni-Suif/01) and the Israeli strain (IS/1494/2006). The second subgroup (Egy/Var-II) included the viruses circulating in the Middle East (Ck/EG/BSU-2 and Ck/EG/BSU-3/2011) and the Israeli strain (IS/885/00). The two variant subgroups (Egy/Var-I and Egy/Var-II) found to be highly pathogenic to SPF chicks with mortalities up to 50% than those of the classic group which was of low virulence (10% mortality). Pathogenicity indices were 25 (Egy/Var-II), 24 (Egy/Var-I) and 8 (classic); with clinical scores 3, 2 and 1 respectively. CONCLUSION: These findings indicated that the recent circulating Egyptian IBVs have multiple heterogeneous origins in marked diversifying nature of their spread, with high pathotype in specific pathogen free chicks.",,"['Zanaty, Ali', 'Arafa, Abdel-Satar', 'Hagag, Naglaa', 'El-Kady, Magdy']",,,,
,PMC,Effects of free amino acids on cytokine secretion and proliferative activity of feline T cells in an in vitro study using the cell line MYA-1,http://dx.doi.org/10.1007/s10616-016-0008-9,PMC5023574,,,"In vitro studies might be an interesting screening method for targeted in vivo studies in the field of immunonutrition and help to reduce and refine animal studies. As the role of amino acids for immune function of cats has not been evaluated in detail so far, the present study aimed at investigating the effects of eight different amino acids (arginine, leucine, isoleucine, valine, glutamine, lysine, threonine and tryptophan) in six concentrations each (0, 0.25, 0.5, 1, 2 and 8x the cat blood level) on cytokine secretion and proliferative activity of feline T cells (MYA-1) in vitro. The results demonstrated that high doses of arginine increased IL-4, IL-10 and TNF-α secretion of T cells, while increasing concentrations of lysine increased IL-10 secretion and proliferative activity of the T cells. High doses of leucine enhanced GM-CSF and IL-10 secretion, while concentrations of threonine in the cell culture media greater than blood concentration also increased GM-CSF and additionally TNF-α secretion of the cells. The effects of glutamine and isoleucine on T cell function were only small. In conclusion, the present in vitro study could evaluate the immunomodulating potential of specific amino acids for feline T cell function. High doses of arginine, lysine, leucine and threonine had a significant impact on cytokine secretion and proliferative activity of the T cells. Targeted in vivo studies should investigate the clinical relevance of dietary supplementation of those amino acids in healthy and diseased cats as a next step.",,"['Paßlack, Nadine', 'Doherr, Marcus G.', 'Zentek, Jürgen']",,,,
,PMC,Toll‐like receptor‐2 exacerbates murine acute viral hepatitis,http://dx.doi.org/10.1111/imm.12627,PMC5011685,,,"Viral replication in the liver is generally detected by cellular endosomal Toll‐like receptors (TLRs) and cytosolic helicase sensors that trigger antiviral inflammatory responses. Recent evidence suggests that surface TLR2 may also contribute to viral detection through recognition of viral coat proteins but its role in the outcome of acute viral infection remains elusive. In this study, we examined in vivo the role of TLR2 in acute infections induced by the highly hepatotrophic mouse hepatitis virus (MHV) type 3 and weakly hepatotrophic MHV‐A59 serotype. To address this, C57BL/6 (wild‐type; WT) and TLR2 knockout (KO) groups of mice were intraperitoneally infected with MHV3 or MHV‐A59. MHV3 infection provoked a fulminant hepatitis in WT mice, characterized by early mortality and high alanine and aspartate transaminase levels, histopathological lesions and viral replication whereas infection of TLR2 KO mice was markedly less severe. MHV‐A59 provoked a comparable mild and subclinical hepatitis in WT and TLR2 KO mice. MHV3‐induced fulminant hepatitis in WT mice correlated with higher hepatic expression of interferon‐β, interleukin‐6, tumour necrosis factor‐α, CXCL1, CCL2, CXCL10 and alarmin (interleukin‐33) than in MHV‐A59‐infected WT mice and in MHV3‐infected TLR2 KO mice. Intrahepatic recruited neutrophils, natural killer cells, natural killer T cells or macrophages rapidly decreased in MHV3‐infected WT mice whereas they were sustained in MHV‐A59‐infected WT mice and MHV3‐infected TLR2 KO. MHV3 in vitro infection of macrophagic cells induced rapid and higher viral replication and/or interleukin‐6 induction in comparison to MHV‐A59, and depended on viral activation of TLR2 and p38 mitogen‐activated protein kinase. Taken together, these results support a new aggravating inflammatory role for TLR2 in MHV3‐induced acute fulminant hepatitis.",,"['Bleau, Christian', 'Burnette, Mélanie', 'Filliol, Aveline', 'Piquet‐Pellorce, Claire', 'Samson, Michel', 'Lamontagne, Lucie']",,,,
,PMC,Screening of a composite library of clinically used drugs and well-characterized pharmacological compounds for cystathionine β-synthase inhibition identifies benserazide as a drug potentially suitable for repurposing for the experimental therapy of colon cancer,http://dx.doi.org/10.1016/j.phrs.2016.08.016,PMC5107130,,,"Cystathionine-β-synthase (CBS) has been recently identified as a drug target for several forms of cancer. Currently no potent and selective CBS inhibitors are available. Using a composite collection of 8871 clinically used drugs and well-annotated pharmacological compounds (including the LOPAC library, the FDA Approved Drug Library, the NIH Clinical Collection, the New Prestwick Chemical Library, the US Drug Collection, the International Drug Collection, the `Killer Plates' collection and a small custom collection of PLP-dependent enzyme inhibitors), we conducted an in vitro screen in order to identify inhibitors for CBS using a primary 7-azido-4-methylcoumarin (AzMc) screen to detect CBS-derived hydrogen sulfide (H(2)S) production. Initial hits were subjected to counterscreens using the methylene blue assay (a secondary assay to measure H(2)S production) and were assessed for their ability to quench the H(2)S signal produced by the H(2)S donor compound GYY4137. Four compounds, hexachlorophene, tannic acid, aurintricarboxylic acid and benserazide showed concentration-dependent CBS inhibitory actions without scavenging H(2)S released from GYY4137, identifying them as direct CBS inhibitors. Hexachlorophene (IC(50): ~60 μM), tannic acid (IC(50): ~40 μM) and benserazide (IC(50): ~30 μM) were less potent CBS inhibitors than the two reference compounds AOAA (IC(50): ~3 μM) and NSC67078 (IC(50): ~1 μM), while aurintricarboxylic acid (IC(50): ~3 μM) was equipotent with AOAA. The second reference compound NSC67078 not only inhibited the CBS-induced AzMC fluorescence signal (IC(50): ~1 μM), but also inhibited with the GYY4137-induced AzMC fluorescence signal with (IC(50) of ~6 μM) indicative of scavenging/non-specific effects. Hexachlorophene (IC(50): ~6 μM), tannic acid (IC(50): ~20 μM), benserazide (IC(50): ~20 μM), and NSC67078 (IC(50): ~0.3 μM) inhibited HCT116 colon cancer cells proliferation with greater potency than AOAA (IC(50): ~300 μM). In contrast, although a CBS inhibitor in the cell-free assay, aurintricarboxylic acid failed to inhibit HCT116 proliferation at lower concentrations, and stimulated cell proliferation at 300 μM. Copper-containing compounds present in the libraries, were also found to be potent inhibitors of recombinant CBS; however this activity was due to the CBS inhibitory effect of copper ions themselves. However, copper ions, up to 300 μM, did not inhibit HCT116 cell proliferation. Benserazide was only a weak inhibitor of the activity of the other H(2)S-generating enzymes CSE and 3-MST activity (16% and 35% inhibition at 100 μM, respectively) in vitro. Benserazide suppressed HCT116 mitochondrial function and inhibited proliferation of the high CBS-expressing colon cancer cell line HT29, but not the low CBS-expressing line, LoVo. The major benserazide metabolite 2,3,4-trihydroxybenzylhydrazine also inhibited CBS activity and suppressed HCT116 cell proliferation in vitro. In an in vivo study of nude mice bearing human colon cancer cell xenografts, benserazide (50 mg/kg/day s.q.) prevented tumor growth. In silico docking simulations showed that benserazide binds in the active site of the enzyme and reacts with the PLP cofactor by forming reversible but kinetically stable Schiff base-like adducts with the formyl moiety of pyridoxal. We conclude that benserazide inhibits CBS activity and suppresses colon cancer cell proliferation and bioenergetics in vitro, and tumor growth in vivo. Further pharmacokinetic, pharmacodynamic and preclinical animal studies are necessary to evaluate the potential of repurposing benserazide for the treatment of colorectal cancers.",,"['Druzhyna, Nadiya', 'Szczesny, Bartosz', 'Olah, Gabor', 'Módis, Katalin', 'Asimakopoulou, Antonia', 'Pavlidou, Athanasia', 'Szoleczky, Petra', 'Gerö, Domokos', 'Yanagi, Kazunori', 'Törö, Gabor', 'López-García, Isabel', 'Myrianthopoulos, Vassilios', 'Mikros, Emmanuel', 'Zatarain, John R.', 'Chao, Celia', 'Papapetropoulos, Andreas', 'Hellmich, Mark R.', 'Szabo, Csaba']",,,,
,PMC,Anti-Influenza Treatment: Drugs Currently Used and Under Development,http://dx.doi.org/10.1016/j.arbres.2016.07.004,PMC6889083,,,"Influenza is a very common contagious disease that carries significant morbidity and mortality. Treatment with antiviral drugs is available, which if administered early, can reduce the risk of severe complications. However, many virus types develop resistance to those drugs, leading to a notable loss of efficacy. There has been great interest in the development of new drugs to combat this disease. A wide range of drugs has shown anti-influenza activity, but they are not yet available for use in the clinic. Many of these target viral components, which others are aimed at elements in the host cell which participate in the viral cycle. Modulating host components is a strategy which minimizes the development of resistance, since host components are not subject to the genetic variability of the virus. The main disadvantage is the risk of treatment-related side effects. The aim of this review is to describe the main pharmacological agents currently available and new drugs in the pipeline with potential benefit in the treatment of influenza.",,"['Amarelle, Luciano', 'Lecuona, Emilia', 'Sznajder, Jacob I.']",,,,
,PMC,Integration of Global Analyses of Host Molecular Responses with Clinical Data To Evaluate Pathogenesis and Advance Therapies for Emerging and Re-emerging Viral Infections,http://dx.doi.org/10.1021/acsinfecdis.6b00104,PMC6131701,,,"Outbreaks associated with emerging and re-emerging viral pathogens continue to increase in frequency and are associated with an increasing burden to global health. In light of this, there is a need to integrate basic and clinical research for investigating the connections between molecular and clinical pathogenesis and for therapeutic development strategies. Here, we will discuss this approach with a focus on the emerging viral pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and monkeypox virus (MPXV) from the context of clinical presentation, immunological and molecular features of the diseases, and OMICS-based analyses of pathogenesis. Furthermore, we will highlight the role of global investigations of host kinases, the kinome, for investigating emerging and re-emerging viral pathogens from the context of characterizing cellular responses and identifying novel therapeutic targets. Lastly, we will address how increased integration of clinical and basic research will assist treatment and prevention efforts for emerging pathogens.",,"['Falcinelli, Shane D.', 'Chertow, Daniel S.', 'Kindrachuk, Jason']",,,,
,PMC,"Economic growth, urbanization, globalization, and the risks of emerging infectious diseases in China: A review",http://dx.doi.org/10.1007/s13280-016-0809-2,PMC5226902,,,"Three interrelated world trends may be exacerbating emerging zoonotic risks: income growth, urbanization, and globalization. Income growth is associated with rising animal protein consumption in developing countries, which increases the conversion of wild lands to livestock production, and hence the probability of zoonotic emergence. Urbanization implies the greater concentration and connectedness of people, which increases the speed at which new infections are spread. Globalization—the closer integration of the world economy—has facilitated pathogen spread among countries through the growth of trade and travel. High-risk areas for the emergence and spread of infectious disease are where these three trends intersect with predisposing socioecological conditions including the presence of wild disease reservoirs, agricultural practices that increase contact between wildlife and livestock, and cultural practices that increase contact between humans, wildlife, and livestock. Such an intersection occurs in China, which has been a “cradle” of zoonoses from the Black Death to avian influenza and SARS. Disease management in China is thus critical to the mitigation of global zoonotic risks.",,"['Wu, Tong', 'Perrings, Charles', 'Kinzig, Ann', 'Collins, James P.', 'Minteer, Ben A.', 'Daszak, Peter']",,,,
,PMC,GENOMIC ANALYSIS OF VIRAL OUTBREAKS,http://dx.doi.org/10.1146/annurev-virology-110615-035747,PMC5210220,,,"Genomic analysis is a powerful tool for understanding viral disease outbreaks. Sequencing of viral samples is now easier and cheaper than ever before, and can supplement epidemiological methods by providing nucleotide-level resolution of outbreak-causing pathogens. In this review, we describe methods used to answer crucial questions about outbreaks, such as how they began and how a disease is transmitted. More specifically, we explain current techniques for viral sequencing, phylogenetic analysis, transmission reconstruction, and evolutionary investigation of viral pathogens. By detailing the ways in which genomic data can help understand viral disease outbreaks, we aim to provide a resource that will facilitate the response to future outbreaks.",,"['Wohl, Shirlee', 'Schaffner, Stephen F.', 'Sabeti, Pardis C.']",,,,
,PMC,Kawasaki disease: a matter of innate immunity,http://dx.doi.org/10.1111/cei.12832,PMC5054572,,,"Kawasaki disease (KD) is an acute systemic vasculitis of childhood that does not have a known cause or aetiology. The epidemiological features (existence of epidemics, community outbreaks and seasonality), unique age distribution and clinical symptoms and signs of KD suggest that the disease is caused by one or more infectious environmental triggers. However, KD is not transmitted person‐to‐person and does not occur in clusters within households, schools or nurseries. KD is a self‐limited illness that is not associated with the production of autoantibodies or the deposition of immune complexes, and it rarely recurs. Regarding the underlying pathophysiology of KD, innate immune activity (the inflammasome) is believed to play a role in the development of KD vasculitis, based on the results of studies with animal models and the clinical and laboratory findings of KD patients. Animal studies have demonstrated that innate immune pathogen‐associated molecular patterns (PAMPs) can cause vasculitis independently of acquired immunity and have provided valuable insights regarding the underlying mechanisms of this phenomenon. To validate this concept, we recently searched for KD‐specific PAMPs and identified such molecules with high specificity and sensitivity. These molecules have structures similar to those of microbe‐associated molecular patterns (MAMPs), as shown by liquid chromatography‐tandem mass spectrometry. We propose herein that KD is an innate immune disorder resulting from the exposure of a genetically predisposed individual to microbe‐derived innate immune stimulants and that it is not a typical infectious disease.",,"['Hara, T.', 'Nakashima, Y.', 'Sakai, Y.', 'Nishio, H.', 'Motomura, Y.', 'Yamasaki, S.']",,,,
,PMC,The pathological significance of dipeptidyl peptidase-4 in endothelial cell homeostasis and kidney fibrosis,http://dx.doi.org/10.1007/s13340-016-0281-z,PMC6224988,,,"Endothelial dysfunction and tubulointerstitial fibrosis are characteristics of diabetic kidneys. Recent evidence has suggested that the diabetic kidney is associated with dipeptidyl peptidase (DPP)-4 overexpression in endothelial cells. Several insults can induce endothelial cells to alter their phenotype into a mesenchymal-like phenotype via endothelial–mesenchymal transition (EndMT), which plays pivotal roles in tissue fibrosis. We have recently revealed the fibrogenic role of DPP-4 through the induction of EndMT in diabetic kidneys. This review mainly focuses on the biological and pathological significance of DPP-4 overexpression in endothelial cells through the mechanisms of endothelial homeostasis defects, EndMT, and kidney fibrosis.",,"Kanasaki, Keizo",,,,
,PMC,Universal Mask Usage for Reduction of Respiratory Viral Infections After Stem Cell Transplant: A Prospective Trial,http://dx.doi.org/10.1093/cid/ciw451,PMC5036914,,,"Background. Respiratory viral infections (RVIs) are frequent complications of hematopoietic stem cell transplant (HSCT). Surgical masks are a simple and inexpensive intervention that may reduce nosocomial spread. Methods. In this prospective single-center study, we instituted a universal surgical mask policy requiring all individuals with direct contact with HSCT patients to wear a surgical mask, regardless of symptoms or season. The primary endpoint was the incidence of RVIs in the mask period (2010–2014) compared with the premask period (2003–2009). Results. RVIs decreased from 10.3% (95/920 patients) in the premask period to 4.4% (40/911) in the mask period (P < .001). Significant decreases occurred after both allogeneic (64/378 [16.9%] to 24/289 [8.3%], P = .001) and autologous (31/542 [5.7%] to 16/622 [2.6%], P = .007) transplants. After adjusting for multiple covariates including season and year in a segmented longitudinal analysis, the decrease in RVIs remained significant, with risk of RVI of 0.4 in patients in the mask group compared with the premask group (0.19–0.85, P = .02). In contrast, no decrease was observed during this same period in an adjacent hematologic malignancy unit, which followed the same infection control practices except for the mask policy. The majority of this decrease was in parainfluenza virus 3 (PIV3) (8.3% to 2.2%, P < .001). Conclusions. Requiring all individuals with direct patient contact to wear a surgical mask is associated with a reduction in RVIs, particularly PIV3, during the most vulnerable period following HSCT.",,"['Sung, Anthony D.', 'Sung, Julia A. M.', 'Thomas, Samantha', 'Hyslop, Terry', 'Gasparetto, Cristina', 'Long, Gwynn', 'Rizzieri, David', 'Sullivan, Keith M.', 'Corbet, Kelly', 'Broadwater, Gloria', 'Chao, Nelson J.', 'Horwitz, Mitchell E.']",,,,
,PMC,Ebola Virus Infection: a review on the pharmacokinetic and pharmacodynamic properties of drugs considered for testing in human efficacy trials,http://dx.doi.org/10.1007/s40262-015-0364-1,PMC5680399,,,"The 2014–2015 outbreak of Ebola virus disease (EVD) is the largest epidemic to date in terms of number of cases, of death and affected areas. In October 2015, no antiviral agents had proven an antiviral efficacy in patients. However in September 2014 WHO inventoried and regularly updated since then a list of potential drug candidates with demonstrated antiviral efficacy in vitro or in animal models. This includes agents belonging to various therapeutic classes, namely direct antiviral agents (favipiravir and BCX4430), combination of antibodies (ZMapp), type I interferons, RNA interference-based drugs (TKM-Ebola and AVI-7537) and anticoagulant drug (rNAPc2). Here, we review the pharmacokinetic and pharmacodynamic information that are presently available on these drugs, using data obtained in healthy volunteers for pharmacokinetics and data obtained in human clinical trials or animal models for pharmacodynamics. Future studies evaluating these drugs in clinical trials will be critical to confirm their efficacy in humans, propose appropriate doses and evaluate the possibility of treatment combinations.",,"['Madelain, Vincent', 'Nguyen, Thi Huyen Tram', 'Olivo, Anaelle', 'De Lamballerie, Xavier', 'Guedj, Jeremie', 'Taburet, Anne-Marie', 'Mentré, France']",,,,
,PMC,TepiTool: A pipeline for computational prediction of T cell epitope candidates,http://dx.doi.org/10.1002/cpim.12,PMC4981331,,,"Computational prediction of T-cell epitope candidates is currently being used in several applications including vaccine discovery studies, development of diagnostics and removal of unwanted immune responses against protein therapeutics. There have been continuous improvements on the performance of MHC binding prediction tools but their general adoption by immunologists has been slow due to the lack of user-friendly interfaces and guidelines. Current tools only provide minimal advice on what alleles to include, what lengths to consider, how to deal with homologous peptides and what cutoffs should be considered relevant. This protocol provides step-by-step instructions with necessary recommendations for prediction of the best T-cell epitope candidates in line with the newly developed online tool called TepiTool. The TepiTool, part of IEDB, provides some of the top MHC binding prediction algorithms for number of species including humans, chimpanzees, bovines, gorillas, macaques, mice and pigs. The TepiTool is freely accessible at http://tools.iedb.org/tepitool/.",,"['Paul, Sinu', 'Sidney, John', 'Sette, Alessandro', 'Peters, Bjoern']",,,,
,PMC,Prevalence and risk factors of pneumothorax among patients admitted to a Pediatric Intensive Care Unit,http://dx.doi.org/10.4103/0972-5229.188191,PMC4994124,27630456,CC BY-NC-SA,"OBJECTIVE: Pneumothorax should be considered a medical emergency and requires a high index of suspicion and prompt recognition and intervention. AIMS: The objective of the study was to evaluate cases developing pneumothorax following admission to a Pediatric Intensive Care Unit (PICU) over a 5-year period. SETTINGS AND DESIGN: Case notes of all PICU patients (n = 1298) were reviewed, revealing that 135 cases (10.4%) developed pneumothorax, and these were compared with those patients who did not. The most common tool for diagnosis used was chest X-ray followed by a clinical examination. SUBJECTS AND METHODS: Case notes of 1298 patients admitted in PICU over 1-year study. RESULTS: Patients with pneumothorax had higher mortality rate (P < 0.001), longer length of stay (P < 0.001), higher need for mechanical ventilation (MV) (P < 0.001), and were of younger age (P < 0.001), lower body weight (P < 0.001), higher pediatric index of mortality 2 score on admission (P < 0.001), higher pediatric logistic organ dysfunction score (P < 0.001), compared to their counterpart. Iatrogenic pneumothorax (IP) represented 95% of episodes of pneumothorax. The most common causes of IP were barotrauma secondary to MV, central vein catheter insertion, and other (69.6%, 13.2%, and 17.2%, respectively). Compared to ventilated patients without pneumothorax, ventilated patients who developed pneumothorax had a longer duration of MV care (P < 0.001) and higher nonconventional and high-frequency oscillatory ventilation settings (P < 0.001). CONCLUSIONS: This study demonstrated that pneumothorax is common in Alexandria University PICU patients, especially in those on MV and emphasized the importance of the strict application of protective lung strategies among ventilated patients to minimize the risk of pneumothorax.",2016 Aug,"['El-Nawawy, Ahmed Ahmed', 'Al-Halawany, Amina Sedky', 'Antonios, Manal Abdelmalik', 'Newegy, Reem Gamal']",Indian J Crit Care Med,,,
,PMC,Metagenomic characterization of the virome associated with bovine respiratory disease in feedlot cattle identified novel viruses and suggests an etiologic role for influenza D virus,http://dx.doi.org/10.1099/jgv.0.000492,PMC5772826,,,"Bovine respiratory disease (BRD) is the most costly disease affecting the cattle industry. The pathogenesis of BRD is complex and includes contributions from microbial pathogens as well as host, environmental and animal management factors. In this study, we utilized viral metagenomic sequencing to explore the virome of nasal swab samples obtained from feedlot cattle with acute BRD and asymptomatic pen-mates at six and four feedlots in Mexico and the USA, respectively, in April–October 2015. Twenty-one viruses were detected, with bovine rhinitis A (52.7 %) and B (23.7 %) virus, and bovine coronavirus (24.7 %) being the most commonly identified. The emerging influenza D virus (IDV) tended to be significantly associated (P=0.134; odds ratio=2.94) with disease, whereas viruses commonly associated with BRD such as bovine viral diarrhea virus, bovine herpesvirus 1, bovine respiratory syncytial virus and bovine parainfluenza 3 virus were detected less frequently. The detection of IDV was further confirmed using a real-time PCR assay. Nasal swabs from symptomatic animals had significantly more IDV RNA than those collected from healthy animals (P=0.04). In addition to known viruses, new genotypes of bovine rhinitis B virus and enterovirus E were identified and a newly proposed species of bocaparvovirus, Ungulate bocaparvovirus 6, was characterized. Ungulate tetraparvovirus 1 was also detected for the first time in North America to our knowledge. These results illustrate the complexity of the virome associated with BRD and highlight the need for further research into the contribution of other viruses to BRD pathogenesis.",,"['Mitra, Namita', 'Cernicchiaro, Natalia', 'Torres, Siddartha', 'Li, Feng', 'Hause, Ben M.']",,,,
,PMC,The contribution of the cytoplasmic retrieval signal of severe acute respiratory syndrome coronavirus to intracellular accumulation of S proteins and incorporation of S protein into virus-like particles,http://dx.doi.org/10.1099/jgv.0.000494,PMC5764123,,,"The cytoplasmic tails of some coronavirus (CoV) spike (S) proteins contain an endoplasmic reticulum retrieval signal (ERRS) that can retrieve S proteins from the Golgi to the endoplasmic reticulum (ER); this process is thought to accumulate S proteins at the CoV budding site, the ER-Golgi intermediate compartment (ERGIC), and to facilitate S protein incorporation into virions. However, we showed previously that porcine epidemic diarrhoea CoV S proteins lacking the ERRS were efficiently incorporated into virions, similar to the original virus. Thus, the precise role of the ERRS in virus assembly remains unclear. Here, the roles of the S protein ERRS in severe acute respiratory syndrome CoV (SARS-CoV) intracellular trafficking and S incorporation into virus-like particles (VLPs) are described. Intracellular trafficking and indirect immunofluorescence analysis suggested that when M protein was present, wild-type S protein (wtS) could be retained in the pre- and post-medial Golgi compartments intracellularly and co-localized with M protein in the Golgi. In contrast, mutant S protein lacking the ERRS was distributed throughout the ER and only partially co-localized with M protein. Moreover, the intracellular accumulation of mutant S protein, particularly at the post-medial Golgi compartment, was significantly reduced compared with wtS. A VLP assay suggested that wtS that reached the post-medial compartment could be returned to the ERGIC for subsequent incorporation into VLPs, while mutant S protein could not. These results suggest that the ERRS of SARS-CoV contributes to intracellular S protein accumulation specifically in the post-medial Golgi compartment and to S protein incorporation into VLPs.",,"['Ujike, Makoto', 'Huang, Cheng', 'Shirato, Kazuya', 'Makino, Shinji', 'Taguchi, Fumihiro']",,,,
,PMC,Fatostatin blocks ER exit of SCAP but inhibits cell growth in a SCAP-independent manner,http://dx.doi.org/10.1194/jlr.M069583,PMC4959871,,,"Sterol regulatory element-binding protein (SREBP) transcription factors are central regulators of cellular lipid homeostasis and activate expression of genes required for fatty acid, triglyceride, and cholesterol synthesis and uptake. SREBP cleavage activating protein (SCAP) plays an essential role in SREBP activation by mediating endoplasmic reticulum (ER)-to-Golgi transport of SREBP. In the Golgi, membrane-bound SREBPs are cleaved sequentially by the site-1 and site-2 proteases. Recent studies have shown a requirement for the SREBP pathway in the development of fatty liver disease and tumor growth, making SCAP a target for drug development. Fatostatin is a chemical inhibitor of the SREBP pathway that directly binds SCAP and blocks its ER-to-Golgi transport. In this study, we determined that fatostatin blocks ER exit of SCAP and showed that inhibition is independent of insulin-induced gene proteins, which function to retain the SCAP-SREBP complex in the ER. Fatostatin potently inhibited cell growth, but unexpectedly exogenous lipids failed to rescue proliferation of fatostatin-treated cells. Furthermore, fatostatin inhibited growth of cells lacking SCAP. Using a vesicular stomatitis virus glycoprotein (VSVG) trafficking assay, we demonstrated that fatostatin delays ER-to-Golgi transport of VSVG. In summary, fatostatin inhibited SREBP activation, but fatostatin additionally inhibited cell proliferation through both lipid-independent and SCAP-independent mechanisms, possibly by general inhibition of ER-to-Golgi transport.",,"['Shao (邵威), Wei', 'Machamer, Carolyn E.', 'Espenshade, Peter J.']",,,,
,PMC,Drug and Device News,,PMC4959614,,,"Approvals, new indications, regulatory activities, and more",,,,,,
,PMC,Effects of Sialic Acid Modifications on Virus Binding and Infection,http://dx.doi.org/10.1016/j.tim.2016.07.005,PMC5123965,,,"Sialic acids (Sias) are abundantly displayed on the surfaces of vertebrate cells, and particularly on all mucosal surfaces. Sias interact with microbes of many types, and are the targets of specific recognition by many different viruses. They may mediate virus binding and infection of cells, or alternatively can act as decoy receptors that bind virions and block virus infection. These nine-carbon backbone monosaccharides naturally occur in many different modified forms, and are attached to underlying glycans through varied linkages, creating significant diversity in the pathogen receptor forms. Here we review the current knowledge regarding the distribution of modified Sias in different vertebrate hosts, tissues, and cells, their effects on viral pathogens where those have been examined, and outline unresolved questions.",,"['Wasik, Brian R', 'Barnard, Karen N', 'Parrish, Colin R']",,,,
,PMC,Prevalence of Respiratory Protective Devices in U.S. Health Care Facilities: Implications for Emergency Preparedness,http://dx.doi.org/10.1177/2165079916657108,PMC4976391,,,"An online questionnaire was developed to explore respiratory protective device (RPD) prevalence in U.S. health care facilities. The survey was distributed to professional nursing society members in 2014 and again in 2015 receiving 322 and 232 participant responses, respectively. The purpose of this study was to explore if the emergency preparedness climate associated with Ebola virus disease changed the landscape of RPD use and awareness. Comparing response percentages from the two sampling time frames using bivariate analysis, no significant changes were found in types of RPDs used in health care settings. N95 filtering facepiece respirators continue to be the most prevalent RPD used in health care facilities, but powered air-purifying respirators are also popular, with regional use highest in the West and Midwest. Understanding RPD use prevalence could ensure that health care workers receive appropriate device trainings as well as improve supply matching for emergency RPD stockpiling.",,"['Wizner, Kerri', 'Stradtman, Lindsay', 'Novak, Debra', 'Shaffer, Ronald']",,,,
,PMC,Antimalarial mass drug administration: ethical considerations,http://dx.doi.org/10.1093/inthealth/ihw027,PMC4967848,,,"Falciparum malaria is a major cause of death and illness in tropical countries, particularly in childhood. In endemic countries, a significant proportion of the community is infected with malaria asymptomatically. One promising way to eliminate malaria is to give the entire population malaria treatment. This is called mass drug administration (MDA) and it raises a number of ethical issues, as possible long-term benefits are uncertain. The effectiveness of MDA is critically dependent on level of participation, so the promised benefits to the community can be annulled by non-participation of a small number of individuals. These potential benefits range a wide spectrum, from the permanent elimination of malaria (success) to a transient reduction in the prevalence of infection and the incidence of illness (failure). The drawbacks of MDA are: inconvenience, potential toxicity, loss of confidence in the elimination campaign, possible drug resistance (though highly unlikely), and the potential for a rebound of malaria illness (if immunity is lost and malaria is reintroduced later). Other ethical issues are related to balancing individual and public health interests, and potentially limiting individual autonomy by making MDA compulsory.",,"['Cheah, Phaik Yeong', 'White, Nicholas J']",,,,
,PMC,Analysis of Ebola virus polymerase domains to find strain-specific differences and to gain insight on their pathogenicity,http://dx.doi.org/10.1007/s13337-016-0334-8,PMC5394698,,,"Ebola virus, a member of the family Filoviridae has caused immense morbidity and mortality in recent times, especially in West Africa. The infection characterized by chills, fever, diarrhea, and myalgia can progress to hemorrhage and death. Hence, it is a high priority area to better understand its biology in order to expedite vaccine development pipelines. In this regard, this study analyzes the domains in RNA polymerase of fifteen publicly-available Ebola isolates belonging to three strains (Zaire, Sudan and Reston). The protein FASTA sequences of the isolates belonging Zaire, Sudan and Reston strains were extracted from UniProt database and submitted to the interactive web tool SMART for the polymerase domain profiles. Subsequent in silico investigation furnished interesting results that sure can contribute to the understanding of Ebola pathogenesis. The key findings and patterns have been presented, and based on them hypotheses have been formulated for further empirical validation.",,"['Patel, Seema', 'Patel, Snigdha']",,,,
,PMC,Ammonia as an In Situ Sanitizer: Influence of Virus Genome Type on Inactivation,http://dx.doi.org/10.1128/AEM.01106-16,PMC4968548,,,"Treatment of human excreta and animal manure (HEAM) is key in controlling the spread of persistent enteric pathogens, such as viruses. The extent of virus inactivation during HEAM storage and treatment appears to vary with virus genome type, although the reasons for this variability are not clear. Here, we investigated the inactivation of viruses of different genome types under conditions representative of HEAM storage or mesophilic digestion. The goals were to characterize the influence of HEAM solution conditions on inactivation and to determine the potential mechanisms involved. Specifically, eight viruses representing the four viral genome types (single-stranded RNA [ssRNA], double-stranded RNA [dsRNA], single-stranded DNA [ssDNA], and double-stranded DNA [dsDNA]) were exposed to synthetic solutions with well-controlled temperature (20 to 35°C), pH (8 to 9), and ammonia (NH(3)) concentrations (0 to 40 mmol liter(−1)). DNA and dsRNA viruses were considerably more resistant than ssRNA viruses, resulting in up to 1,000-fold-longer treatment times to reach a 4-log inactivation. The apparently slower inactivation of DNA viruses was rationalized by the higher stability of DNA than that of ssRNA in HEAM. Pushing the system toward harsher pH (>9) and temperature (>35°C) conditions, such as those encountered in thermophilic digestion and alkaline treatments, led to more consistent inactivation kinetics among ssRNA and other viruses. This suggests that the dependence of inactivation on genome type disappeared in favor of protein-mediated inactivation mechanisms common to all viruses. Finally, we recommend the use of MS2 as a conservative indicator to assess the inactivation of ssRNA viruses and the stable ΦX174 or dsDNA phages as indicators for persistent viruses. IMPORTANCE Viruses are among the most environmentally persistent pathogens. They can be present in high concentrations in human excreta and animal manure (HEAM). Therefore, appropriate treatment of HEAM is important prior to its reuse or discharge into the environment. Here, we investigated the factors that determine the persistence of viruses in HEAM, and we determined the main mechanisms that lead to their inactivation. Unlike other organisms, viruses can have four different genome types (double- or single-stranded RNA or DNA), and the viruses studied herein represent all four types. Genome type appeared to be the major determinant for persistence. Single-stranded RNA viruses are the most labile, because this genome type is susceptible to degradation in HEAM. In contrast, the other genome types are more stable; therefore, inactivation is slower and mainly driven by the degradation of viral proteins. Overall, this study allows us to better understand the behavior of viruses in HEAM.",,"['Decrey, Loïc', 'Kazama, Shinobu', 'Kohn, Tamar']",,,,
,PMC,Humoral Innate Immunity at the Crossroad Between Microbe and Matrix Recognition: The Role of PTX3 in Tissue Damage,http://dx.doi.org/10.1016/j.semcdb.2016.07.026,PMC5419421,,,"Innate immunity is involved in regulating inflammatory and tissue repair responses to injury. In particular, humoral innate immunity plays functions related to wound clearance from tissue debris, and regulation of macrophage and stromal cell activities. PTX3, a component of humoral innate immunity, orchestrates tissue repair by interacting with plasminogen and fibrin. Fluid-phase molecules of innate immunity interact with elements of the extracellular matrix, and some of the latter display opsonic activity against certain bacterial species. Thus, recognition of extracellular matrix and microbial components is a recurrent theme in the humoral arm of the innate immune system.",,"['Doni, Andrea', ""D'Amico, Giovanna"", 'Morone, Diego', 'Mantovani, Alberto', 'Garlanda, Cecilia']",,,,
,PMC,Anti-hepatitis C virus potency of a new autophagy inhibitor using human liver slices model,http://dx.doi.org/10.4254/wjh.v8.i21.902,PMC4958700,,,"AIM: To evaluate the antiviral potency of a new anti-hepatitis C virus (HCV) antiviral agent targeting the cellular autophagy machinery. METHODS: Non-infected liver slices, obtained from human liver resection and cut in 350 μm-thick slices (2.7 × 10(6) cells per slice) were infected with cell culture-grown HCV Con1b/C3 supernatant (multiplicity of infection = 0.1) cultivated for up to ten days. HCV infected slices were treated at day 4 post-infection with GNS-396 for 6 d at different concentrations. HCV replication was evaluated by strand-specific real-time quantitative reverse transcription - polymerase chain reaction. The infectivity titers of supernatants were evaluated by foci formation upon inoculation into naive Huh-7.5.1 cells. The cytotoxic effect of the drugs was evaluated by lactate dehydrogenase leakage assays. RESULTS: The antiviral efficacy of a new antiviral drug, GNS-396, an autophagy inhibitor, on HCV infection of adult human liver slices was evidenced in a dose-dependent manner. At day 6 post-treatment, GNS-396 EC50 was 158 nmol/L without cytotoxic effect (compared to hydroxychloroquine EC50 = 1.17 μmol/L). CONCLUSION: Our results demonstrated that our ex vivo model is efficient for evaluation the potency of autophagy inhibitors, in particular a new quinoline derivative GNS-396 as antiviral could inhibit HCV infection in a dose-dependent manner without cytotoxic effect.",,"['Lagaye, Sylvie', 'Brun, Sonia', 'Gaston, Jesintha', 'Shen, Hong', 'Stranska, Ruzena', 'Camus, Claire', 'Dubray, Clarisse', 'Rousseau, Géraldine', 'Massault, Pierre-Philippe', 'Courcambeck, Jerôme', 'Bassisi, Firas', 'Halfon, Philippe', 'Pol, Stanislas']",,,,
,PMC,Homology-Based Identification of a Mutation in the Coronavirus RNA-Dependent RNA Polymerase That Confers Resistance to Multiple Mutagens,http://dx.doi.org/10.1128/JVI.00080-16,PMC4984655,,,"Positive-sense RNA viruses encode RNA-dependent RNA polymerases (RdRps) essential for genomic replication. With the exception of the large nidoviruses, such as coronaviruses (CoVs), RNA viruses lack proofreading and thus are dependent on RdRps to control nucleotide selectivity and fidelity. CoVs encode a proofreading exonuclease in nonstructural protein 14 (nsp14-ExoN), which confers a greater-than-10-fold increase in fidelity compared to other RNA viruses. It is unknown to what extent the CoV polymerase (nsp12-RdRp) participates in replication fidelity. We sought to determine whether homology modeling could identify putative determinants of nucleotide selectivity and fidelity in CoV RdRps. We modeled the CoV murine hepatitis virus (MHV) nsp12-RdRp structure and superimposed it on solved picornaviral RdRp structures. Fidelity-altering mutations previously identified in coxsackie virus B3 (CVB3) were mapped onto the nsp12-RdRp model structure and then engineered into the MHV genome with [nsp14-ExoN(+)] or without [nsp14-ExoN(−)] ExoN activity. Using this method, we identified two mutations conferring resistance to the mutagen 5-fluorouracil (5-FU): nsp12-M611F and nsp12-V553I. For nsp12-V553I, we also demonstrate resistance to the mutagen 5-azacytidine (5-AZC) and decreased accumulation of mutations. Resistance to 5-FU, and a decreased number of genomic mutations, was effectively masked by nsp14-ExoN proofreading activity. These results indicate that nsp12-RdRp likely functions in fidelity regulation and that, despite low sequence conservation, some determinants of RdRp nucleotide selectivity are conserved across RNA viruses. The results also indicate that, with regard to nucleotide selectivity, nsp14-ExoN is epistatic to nsp12-RdRp, consistent with its proposed role in a multiprotein replicase-proofreading complex. IMPORTANCE RNA viruses have evolutionarily fine-tuned replication fidelity to balance requirements for genetic stability and diversity. Responsibility for replication fidelity in RNA viruses has been attributed to the RNA-dependent RNA polymerases, with mutations in RdRps for multiple RNA viruses shown to alter fidelity and attenuate virus replication and virulence. Coronaviruses (CoVs) are the only known RNA viruses to encode a proofreading exonuclease (nsp14-ExoN), as well as other replicase proteins involved in regulation of fidelity. This report shows that the CoV RdRp (nsp12) likely functions in replication fidelity; that residue determinants of CoV RdRp nucleotide selectivity map to similar structural regions of other, unrelated RNA viral polymerases; and that for CoVs, the proofreading activity of the nsp14-ExoN is epistatic to the function of the RdRp in fidelity.",,"['Sexton, Nicole R.', 'Smith, Everett Clinton', 'Blanc, Hervé', 'Vignuzzi, Marco', 'Peersen, Olve B.', 'Denison, Mark R.']",,,,
,PMC,Mutagenesis of S-Adenosyl-l-Methionine-Binding Residues in Coronavirus nsp14 N7-Methyltransferase Demonstrates Differing Requirements for Genome Translation and Resistance to Innate Immunity,http://dx.doi.org/10.1128/JVI.00542-16,PMC4984653,,,"Eukaryotic mRNAs possess a methylated 5′-guanosine cap that is required for RNA stability, efficient translation, and protection from cell-intrinsic defenses. Many viruses use 5′ caps or other mechanisms to mimic a cap structure to limit detection of viral RNAs by intracellular innate sensors and to direct efficient translation of viral proteins. The coronavirus (CoV) nonstructural protein 14 (nsp14) is a multifunctional protein with N7-methyltransferase (N7-MTase) activity. The highly conserved S-adenosyl-l-methionine (SAM)-binding residues of the DxG motif are required for nsp14 N7-MTase activity in vitro. However, the requirement for CoV N7-MTase activity and the importance of the SAM-binding residues during viral replication have not been determined. Here, we engineered mutations in murine hepatitis virus (MHV) nsp14 N7-MTase at residues D330 and G332 and determined the effects of these mutations on viral replication, sensitivity to mutagen, inhibition by type I interferon (IFN), and translation efficiency. Virus encoding a G332A substitution in nsp14 displayed delayed replication kinetics and decreased peak titers relative to wild-type (WT) MHV. In addition, replication of nsp14 G332A virus was diminished following treatment of cells with IFN-β, and nsp14 G332A genomes were translated less efficiently both in vitro and during viral infection. In contrast, substitution of alanine at MHV nsp14 D330 did not affect viral replication, sensitivity to mutagen, or inhibition by IFN-β compared to WT MHV. Our results demonstrate that the conserved MHV N7-MTase SAM-binding-site residues are not required for MHV viability and suggest that the determinants of CoV N7-MTase activity differ in vitro and during virus infection. IMPORTANCE Human coronaviruses, most notably severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, cause severe and lethal human disease. Since specific antiviral therapies are not available for the treatment of human coronavirus infections, it is essential to understand the functions of conserved CoV proteins in viral replication. Here, we show that substitution of alanine at G332 in the N7-MTase domain of nsp14 impairs viral replication, enhances sensitivity to the innate immune response, and reduces viral RNA translation efficiency. Our data support the idea that coronavirus RNA capping could be targeted for development of antiviral therapeutics.",,"['Case, James Brett', 'Ashbrook, Alison W.', 'Dermody, Terence S.', 'Denison, Mark R.']",,,,
,PMC,Critical Role of the PA-X C-Terminal Domain of Influenza A Virus in Its Subcellular Localization and Shutoff Activity,http://dx.doi.org/10.1128/JVI.00954-16,PMC4984632,,,"PA-X is a recently identified influenza virus protein that is composed of the PA N-terminal 191 amino acids and unique C-terminal 41 or 61 residues. We and others showed that PA-X has a strong ability to suppress host protein synthesis via host mRNA decay, which is mediated by endonuclease activity in its N-terminal domain (B. W. Jagger, H. M. Wise, J. C. Kash, K. A. Walters, N. M. Wills, Y. L. Xiao, R. L. Dunfee, L. M. Schwartzman, A. Ozinsky, G. L. Bell, R. M. Dalton, A. Lo, S. Efstathiou, J. F. Atkins, A. E. Firth, J. K. Taubenberger, and P. Digard, 2012, Science 337:199–204, http://dx.doi.org/10.1126/science.1222213, and E. A. Desmet, K. A. Bussey, R. Stone, and T. Takimoto, 2013, J Virol 87:3108–3118, http://dx.doi.org/10.1128/JVI.02826-12). However, the mechanism of host mRNA degradation, especially where and how PA-X targets mRNAs, has not been analyzed. In this study, we determined the localization of PA-X and the role of the C-terminal unique region in shutoff activity. Quantitative subcellular localization analysis revealed that PA-X was located equally in both cytoplasm and nucleus. By characterizing a series of PA-X C-terminal deletion mutants, we found that the first 9 amino acids were sufficient for nuclear localization, but an additional 6 residues were required to induce the maximum shutoff activity observed with intact PA-X. Importantly, forced nuclear localization of the PA-X C-terminal deletion mutant enhanced shutoff activity, highlighting the ability of nuclear PA-X to degrade host mRNAs more efficiently. However, PA-X also inhibited luciferase expression from transfected mRNAs synthesized in vitro, suggesting that PA-X also degrades mRNAs in the cytoplasm. Among the basic amino acids in the PA-X C-terminal region, 3 residues, 195K, 198K, and 199R, were identified as key residues for inducing host shutoff and nuclear localization. Overall, our data indicate a critical role for the 15 residues in the PA-X C-terminal domain in degrading mRNAs in both the cytoplasm and nucleus. IMPORTANCE Influenza A viruses express PA-X proteins to suppress global host gene expression, including host antiviral genes, to allow efficient viral replication in infected cells. However, little is known about how PA-X induces host shutoff. In this study, we showed that PA-X localized equally in both the cytoplasm and nucleus of the cells, but the nuclear localization of PA-X mediated by its C-terminal region has a significant impact on shutoff activity. Three basic residues at the C-terminal region play a critical role in nuclear localization, but additional basic residues were required for maximum shutoff activity. Our findings indicate that PA-X targets and degrades mRNAs in both the nucleus and cytoplasm, and that the first 15 residues of the PA-X unique C-terminal region play a critical role in shutoff activity.",,"['Hayashi, Tsuyoshi', 'Chaimayo, Chutikarn', 'McGuinness, James', 'Takimoto, Toru']",,,,
,PMC,MAVS Expressed by Hematopoietic Cells Is Critical for Control of West Nile Virus Infection and Pathogenesis,http://dx.doi.org/10.1128/JVI.00707-16,PMC4984631,,,"West Nile virus (WNV) is the most important cause of epidemic encephalitis in North America. Innate immune responses, which are critical for control of WNV infection, are initiated by signaling through pathogen recognition receptors, RIG-I and MDA5, and their downstream adaptor molecule, MAVS. Here, we show that a deficiency of MAVS in hematopoietic cells resulted in increased mortality and delayed WNV clearance from the brain. In Mavs(−/−) mice, a dysregulated immune response was detected, characterized by a massive influx of macrophages and virus-specific T cells into the infected brain. These T cells were polyfunctional and lysed peptide-pulsed target cells in vitro. However, virus-specific T cells in the brains of infected Mavs(−/−) mice exhibited lower functional avidity than those in wild-type animals, and even virus-specific memory T cells generated by prior immunization could not protect Mavs(−/−) mice from WNV-induced lethal disease. Concomitant with ineffective virus clearance, macrophage numbers were increased in the Mavs(−/−) brain, and both macrophages and microglia exhibited an activated phenotype. Microarray analyses of leukocytes in the infected Mavs(−/−) brain showed a preferential expression of genes associated with activation and inflammation. Together, these results demonstrate a critical role for MAVS in hematopoietic cells in augmenting the kinetics of WNV clearance and thereby preventing a dysregulated and pathogenic immune response. IMPORTANCE West Nile virus (WNV) is the most important cause of mosquito-transmitted encephalitis in the United States. The innate immune response is known to be critical for protection in infected mice. Here, we show that expression of MAVS, a key adaptor molecule in the RIG-I-like receptor RNA-sensing pathway, in hematopoietic cells is critical for protection from lethal WNV infection. In the absence of MAVS, there is a massive infiltration of myeloid cells and virus-specific T cells into the brain and overexuberant production of proinflammatory cytokines. These results demonstrate the important role that MAVS expression in hematopoietic cells has in regulating the inflammatory response in the WNV-infected brain.",,"['Zhao, Jincun', 'Vijay, Rahul', 'Zhao, Jingxian', 'Gale, Michael', 'Diamond, Michael S.', 'Perlman, Stanley']",,,,
,PMC,Infectious Bronchitis Coronavirus Limits Interferon Production by Inducing a Host Shutoff That Requires Accessory Protein 5b,http://dx.doi.org/10.1128/JVI.00627-16,PMC4984617,,,"During infection of their host cells, viruses often inhibit the production of host proteins, a process that is referred to as host shutoff. By doing this, viruses limit the production of antiviral proteins and increase production capacity for viral proteins. Coronaviruses from the genera Alphacoronavirus and Betacoronavirus, such as severe acute respiratory syndrome coronavirus (SARS-CoV), establish host shutoff via their nonstructural protein 1 (nsp1). The Gammacoronavirus and Deltacoronavirus genomes, however, do not encode nsp1, and it has been suggested that these viruses do not induce host shutoff. Here, we show that the Gammacoronavirus infectious bronchitis virus (IBV) does induce host shutoff, and we find that its accessory protein 5b is indispensable for this function. Importantly, we found that 5b-null viruses, unlike wild-type viruses, induce production of high concentrations of type I interferon protein in vitro, indicating that host shutoff by IBV plays an important role in antagonizing the host's innate immune response. Altogether, we demonstrate that 5b is a functional equivalent of nsp1, thereby answering the longstanding question of whether lack of nsp1 in gammacoronaviruses is compensated for by another viral protein. As such, our study is a significant step forward in the understanding of coronavirus biology and closes a gap in the understanding of some IBV virulence strategies. IMPORTANCE Many viruses inhibit protein synthesis by their host cell to enhance virus replication and to antagonize antiviral defense mechanisms. This process is referred to as host shutoff. We studied gene expression and protein synthesis in chicken cells infected with the important poultry pathogen infectious bronchitis virus (IBV). We show that IBV inhibits synthesis of host proteins, including that of type I interferon, a key component of the antiviral response. The IBV-induced host shutoff, however, does not require degradation of host RNA. Furthermore, we demonstrate that accessory protein 5b of IBV plays a crucial role in the onset of host shutoff. Our findings suggest that inhibition of host protein synthesis is a common feature of coronaviruses and primarily serves to inhibit the antiviral response of the host.",,"['Kint, Joeri', 'Langereis, Martijn A.', 'Maier, Helena J.', 'Britton, Paul', 'van Kuppeveld, Frank J.', 'Koumans, Joseph', 'Wiegertjes, Geert F.', 'Forlenza, Maria']",,,,
,PMC,PTX3 Deletion Aggravates Allergic Inflammation through a Th17 -Dominant Phenotype and Enhanced CD4 T cell Survival,http://dx.doi.org/10.1016/j.jaci.2016.04.063,PMC6317853,,,"BACKGROUND: Pentraxin 3 (PTX3) is a multifunctional molecule, which plays a non-redundant role at the crossroads between pathogen clearance, innate immune system, matrix deposition, female fertility and vascular biology. It is produced at sites of infection and inflammation by both structural and inflammatory cells. However its role in allergen-induced inflammation remains to be tested. OBJECTIVE: To determine the effect of PTX3 deletion on ovalbumin (OVA)–induced allergic inflammation in a murine model of asthma. METHODS: Bronchoalveolar lavage fluid (BALF) was collected from severe asthmatic and healthy subjects and level of PTX3 was determined by ELISA. PTX3(+/+) and PTX3(−/−) mice were sensitized and challenged with OVA and BALF and the lungs were collected for accessing inflammation. Lung tissue inflammation and mucus production were assessed by flow cytometry, H&E and PAS staining, respectively. FlexiVENT was used to determine airway resistance to methacholine of these mice. RESULTS: Here we report that severe asthmatics and OVA-sensitized/ challenged mice had increased PTX3 level in the lungs compared with healthy controls. Mice lacking PTX3 develop exaggerated neutrophilic/ eosinophilic lung inflammation, mucus production and airway hyperresponsiveness (AHR) in an experimental model of OVA-induced asthma. Furthermore, OVA-exposed lung PTX3(−/−) CD4 T cells exhibit an increased production of IL-17A, an effect that is accompanied with an elevated STAT3 phosphorylation, reduced IL-2 production, enhanced activation and survival. Also we observed increase in IL-6 and IL-23 producing DCs in OVA-exposed PTX3(−/−) mice as compared to their wild type controls. CONCLUSION: Altogether, PTX3 deficiency results in augmented AHR, mucus production and IL-17A-dominant pulmonary inflammation, suggesting a regulatory role of PTX3 in the development of allergic inflammation.",,"['Balhara, Jyoti', 'Shan, Lianyu', 'Zhang, Jingbo', 'Muhuri, Anik', 'Halayko, Andrew J.', 'Almiski, Muhamad S.', 'Doeing, Diana', 'McConville, John', 'Matzuk, Martin M', 'Gounni, Abdelilah S.']",,,,
,PMC,"Design of virus-based nanomaterials for medicine, biotechnology, and energy",http://dx.doi.org/10.1039/c5cs00287g,PMC5068136,,,"Virus-based nanomaterials are versatile materials that naturally self-assemble and have relevance for a broad range of applications including medicine, biotechnology, and energy. This review provides an overview of recent developments in “chemical virology.” Viruses, as materials, provide unique nanoscale scaffolds that have relevance in chemical biology and nanotechnology, with diverse areas of applications. Some fundamental advantages of viruses, compared to synthetically programmed materials, include the highly precise spatial arrangement of their subunits into a diverse array of shapes and sizes and many available avenues for easy and reproducible modification. Here, we will first survey the broad distribution of viruses and various methods for producing virus-based nanoparticles, as well as engineering principles used to impart new functionalities. We will then examine the broad range of applications and implications of virus-based materials, focusing on the medical, biotechnology, and energy sectors. We anticipate that this field will continue to evolve and grow, with exciting new possibilities stemming from advancements in the rational design of virus-based nanomaterials.",,"['Wen, Amy M.', 'Steinmetz, Nicole F.']",,,,
,PMC,Impact of Early Detection of Respiratory Viruses by Multiplex PCR Assay on Clinical Outcomes in Adult Patients,http://dx.doi.org/10.1128/JCM.00549-16,PMC4963510,,,"Rapid and definitive diagnosis of viral respiratory infections is imperative in patient triage and management. We compared the outcomes for adult patients with positive tests for respiratory viruses at a tertiary care center across two consecutive influenza seasons (winters of 2010-2011 and 2012). Infections were diagnosed by conventional methods in the first season and by multiplex PCR (FilmArray) in the second season. FilmArray decreased the time to diagnosis of influenza compared to conventional methods (median turnaround times of 1.7 h versus 7.7 h, respectively; P = 0.015); FilmArray also decreased the time to diagnosis of non-influenza viruses (1.5 h versus 13.5 h, respectively; P < 0.0001). Multivariate logistic regression found that a diagnosis of influenza by FilmArray was associated with significantly lower odds ratios (ORs) for admission (P = 0.046), length of stay (P = 0.040), duration of antimicrobial use (P = 0.032), and number of chest radiographs (P = 0.005), when controlling for potential confounders. We conclude that the rapid turnaround time, multiplex nature of the test (allowing simultaneous detection of an array of viruses), and superior sensitivity of FilmArray may improve the evaluation and management of patients suspected of having respiratory virus infections.",,"['Rappo, Urania', 'Schuetz, Audrey N.', 'Jenkins, Stephen G.', 'Calfee, David P.', 'Walsh, Thomas J.', 'Wells, Martin T.', 'Hollenberg, James P.', 'Glesby, Marshall J.']",,,,
,PMC,A Computationally Designed Serological Assay for Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.1128/JCM.00460-16,PMC4963506,,,"The periodic emergence of new infectious agents and the genetic and antigenic evolution of existing agents necessitate the improvement of technology for the rapid development of diagnostic assays. The porcine epidemic diarrhea virus (PEDV) emerged in the United States in 2013, causing severe economic damage to the pork industry. The primary goal of this study was to develop methods to reduce the lead time for serological assay development. An approach involving the computational prediction of diagnostic targets, followed by a rapid synthesis of antigens, was adopted to achieve this objective. To avoid cross-reactivity with other closely related swine coronaviruses, the N protein sequences of PEDV were analyzed to identify sequences unique to PEDV. The potential antigenicity of the identified sequence was predicted computationally using the Jameson-Wolf method. A sequence with a high antigenic index was rapidly synthesized using an in vitro transcription and translation system to yield the diagnostic antigen. The computationally designed enzyme-linked immunosorbent assay (ELISA) was validated using 169 field sera, whose statuses were determined by a PEDV-specific immunofluorescence assay. Comparison of the computationally designed ELISA to a conventionally developed ELISA, using bacterially expressed N protein, and to the immunofluorescence assay showed a high degree of agreement among the three tests (mean kappa statistic, 0.842). The sensitivity and specificity, compared to the conventionally developed assay, were 90.62 and 95.18, respectively. Therefore, the described approach is useful in reducing the development time for serological assays in the face of an infectious disease outbreak.",,"['Song, Yunfeng', 'Singh, Pankaj', 'Nelson, Eric', 'Ramamoorthy, Sheela']",,,,
,PMC,Feasibility and Operational Performance of Tuberculosis Detection by Loop-Mediated Isothermal Amplification Platform in Decentralized Settings: Results from a Multicenter Study,http://dx.doi.org/10.1128/JCM.03036-15,PMC4963503,,,"Currently available nucleic acid amplification platforms for tuberculosis (TB) detection are not designed to be simple or inexpensive enough to implement in decentralized settings in countries with a high burden of disease. The loop-mediated isothermal amplification platform (LAMP) may change this. We conducted a study in adults with symptoms suggestive of TB in India, Uganda, and Peru to establish the feasibility of using TB-LAMP (Eiken Chemical Co.) in microscopy laboratories compared with using smear microscopy against a reference standard of solid and liquid cultures. Operational characteristics were evaluated as well. A total of 1,777 participants met the eligibility criteria and were included for analysis. Overall, TB-LAMP sensitivities among culture-positive samples were 97.2% (243/250; 95% confidence interval [CI], 94.3% to 98.2%) and 62.0% (88/142; 95% CI, 53.5% to 70.0%) for smear-positive and smear-negative TB, respectively, but varied widely by country and operator. Specificities ranged from 94.5% (446/472; 95% CI, 92.0% to 96.4%) to 98.0% (350/357; 95% CI, 96.0% to 99.2%) by country. A root cause analysis identified high temperatures, high humidity, and/or low reaction volumes as possible causes for false-positive results, as they may result in nonspecific amplification. The study was repeated in India with training focused on vulnerable steps and an updated protocol; 580 participants were included for analysis. Specificity in the repeat trial was 96.6% (515/533; 95% CI, 94.7% to 97.9%). To achieve acceptable performance of LAMP at the microscopy center level, significant training and infrastructure requirements are necessary.",,"['Gray, Christen M.', 'Katamba, Achilles', 'Narang, Pratibha', 'Giraldo, Jorge', 'Zamudio, Carlos', 'Joloba, Moses', 'Narang, Rahul', 'Paramasivan, C. N.', 'Hillemann, Doris', 'Nabeta, Pamela', 'Amisano, Danielle', 'Alland, David', 'Cobelens, Frank', 'Boehme, Catharina C.']",,,,
,PMC,Unraveling the drivers of MERS-CoV transmission,http://dx.doi.org/10.1073/pnas.1519235113,PMC4987807,,,"With more than 1,700 laboratory-confirmed infections, Middle East respiratory syndrome coronavirus (MERS-CoV) remains a significant threat for public health. However, the lack of detailed data on modes of transmission from the animal reservoir and between humans means that the drivers of MERS-CoV epidemics remain poorly characterized. Here, we develop a statistical framework to provide a comprehensive analysis of the transmission patterns underlying the 681 MERS-CoV cases detected in the Kingdom of Saudi Arabia (KSA) between January 2013 and July 2014. We assess how infections from the animal reservoir, the different levels of mixing, and heterogeneities in transmission have contributed to the buildup of MERS-CoV epidemics in KSA. We estimate that 12% [95% credible interval (CI): 9%, 15%] of cases were infected from the reservoir, the rest via human-to-human transmission in clusters (60%; CI: 57%, 63%), within (23%; CI: 20%, 27%), or between (5%; CI: 2%, 8%) regions. The reproduction number at the start of a cluster was 0.45 (CI: 0.33, 0.58) on average, but with large SD (0.53; CI: 0.35, 0.78). It was >1 in 12% (CI: 6%, 18%) of clusters but fell by approximately one-half (47% CI: 34%, 63%) its original value after 10 cases on average. The ongoing exposure of humans to MERS-CoV from the reservoir is of major concern, given the continued risk of substantial outbreaks in health care systems. The approach we present allows the study of infectious disease transmission when data linking cases to each other remain limited and uncertain.",,"['Cauchemez, Simon', 'Nouvellet, Pierre', 'Cori, Anne', 'Jombart, Thibaut', 'Garske, Tini', 'Clapham, Hannah', 'Moore, Sean', 'Mills, Harriet Linden', 'Salje, Henrik', 'Collins, Caitlin', 'Rodriquez-Barraquer, Isabel', 'Riley, Steven', 'Truelove, Shaun', 'Algarni, Homoud', 'Alhakeem, Rafat', 'AlHarbi, Khalid', 'Turkistani, Abdulhafiz', 'Aguas, Ricardo J.', 'Cummings, Derek A. T.', 'Van Kerkhove, Maria D.', 'Donnelly, Christl A.', 'Lessler, Justin', 'Fraser, Christophe', 'Al-Barrak, Ali', 'Ferguson, Neil M.']",,,,
,PMC,Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions,http://dx.doi.org/10.1016/j.taap.2016.07.015,PMC5978774,,,"Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4(+/+) wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immunotoxicity phenotype was not observed in ATO-treated ATF4(+/−)heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca(++) homeostasis. ATO induces Ca(++)-dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca(++) homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic.",,"['Srivastava, Ritesh K.', 'Li, Changzhao', 'Wang, Yong', 'Weng, Zhiping', 'Elmets, Craig A.', 'Harrod, Kevin S.', 'Deshane, Jessy S.', 'Athar, Mohammad']",,,,
,PMC,Identifying Cost-Effective Dynamic Policies to Control Epidemics,http://dx.doi.org/10.1002/sim.7047,PMC5096998,,,"We describe a mathematical decision model for identifying dynamic health policies for controlling epidemics. These dynamic policies aim to select the best current intervention based on accumulating epidemic data and the availability of resources at each decision point. We propose an algorithm to approximate dynamic policies that optimize the population’s net health benefit, a performance measure which accounts for both health and monetary outcomes. We further illustrate how dynamic policies can be defined and optimized for the control of a novel viral pathogen, where a policy maker must decide (i) when to employ or lift a transmission-reducing intervention (e.g. school closure) and (ii) how to prioritize population members for vaccination when a limited quantity of vaccines first become available. Within the context of this application, we demonstrate that dynamic policies can produce higher net health benefit than more commonly described static policies that specify a pre-determined sequence of interventions to employ throughout epidemics.",,"['Yaesoubi, Reza', 'Cohen, Ted']",,,,
,PMC,"Optimization of a Class of Tryptophan Dendrimers That Inhibit HIV Replication Leads to a Selective, Specific, and Low-Nanomolar Inhibitor of Clinical Isolates of Enterovirus A71",http://dx.doi.org/10.1128/AAC.00626-16,PMC4958208,,,"Tryptophan dendrimers that inhibit HIV replication by binding to the HIV envelope glycoproteins gp120 and gp41 have unexpectedly also proven to be potent, specific, and selective inhibitors of the replication of the unrelated enterovirus A71. Dendrimer 12, a consensus compound that was synthesized on the basis of the structure-activity relationship analysis of this series, is 3-fold more potent against the BrCr lab strain and, surprisingly, inhibits a large panel of clinical isolates in the low-nanomolar/high-picomolar range.",,"['Rivero-Buceta, Eva', 'Sun, Liang', 'Martínez-Gualda, Belén', 'Doyagüez, Elisa G.', 'Donckers, Kim', 'Quesada, Ernesto', 'Camarasa, María-José', 'Delang, Leen', 'San-Félix, Ana', 'Neyts, Johan', 'Leyssen, Pieter']",,,,
,PMC,"Screening for transmembrane association in divisome proteins using TOXGREEN, a high-throughput variant of the TOXCAT assay",http://dx.doi.org/10.1016/j.bbamem.2016.07.008,PMC5045792,,,"TOXCAT is a widely used genetic assay to study interactions of transmembrane helices within the inner membrane of the bacterium Escherichia coli. TOXCAT is based on a fusion construct that links a transmembrane domain of interest with a cytoplasmic DNA-binding domain from the Vibrio cholerae ToxR protein. Interaction driven by the transmembrane domain results in dimerization of the ToxR domain, which, in turn, activates the expression of the reporter gene chloramphenicol acetyl transferase (CAT). Quantification of CAT is used as a measure of the ability of the transmembrane domain to self-associate. Because the quantification of CAT is relatively laborious, we developed a high-throughput variant of the assay, TOXGREEN, based on the expression of super-folded GFP and detection of fluorescence directly in unprocessed cell cultures. Careful side-by-side comparison of TOXCAT and TOXGREEN demonstrates that the methods have comparable response, dynamic range, sensitivity and intrinsic variability both in LB and minimal media. The greatly enhanced workflow makes TOXGREEN much more scalable and ideal for screening, since hundreds of constructs can be rapidly assessed in 96 well plates. Even for small scale investigations, TOXGREEN significantly reduces time, labor and cost associated with the procedure. We demonstrate applicability with a large screening for self-association among the transmembrane domains of bitopic proteins of the divisome (FtsL, FtsB, FtsQ, FtsI, FtsN, ZipA and EzrA) belonging to 11 bacterial species. The analysis confirms a previously reported tendency for FtsB to self-associate, and suggests that the transmembrane domains of ZipA, EzrA and FtsN may also possibly oligomerize.",,"['Armstrong, Claire R.', 'Senes, Alessandro']",,,,
,PMC,Macrophage colony-stimulating factor (CSF1) controls monocyte production and maturation and the steady-state size of the liver in pigs,http://dx.doi.org/10.1152/ajpgi.00116.2016,PMC5076001,27445344,CC BY,"Macrophage colony-stimulating factor (CSF1) is an essential growth and differentiation factor for cells of the macrophage lineage. To explore the role of CSF1 in steady-state control of monocyte production and differentiation and tissue repair, we previously developed a bioactive protein with a longer half-life in circulation by fusing pig CSF1 with the Fc region of pig IgG1a. CSF1-Fc administration to pigs expanded progenitor pools in the marrow and selectively increased monocyte numbers and their expression of the maturation marker CD163. There was a rapid increase in the size of the liver, and extensive proliferation of hepatocytes associated with increased macrophage infiltration. Despite the large influx of macrophages, there was no evidence of liver injury and no increase in circulating liver enzymes. Microarray expression profiling of livers identified increased expression of macrophage markers, i.e., cytokines such as TNF, IL1, and IL6 known to influence hepatocyte proliferation, alongside cell cycle genes. The analysis also revealed selective enrichment of genes associated with portal, as opposed to centrilobular regions, as seen in hepatic regeneration. Combined with earlier data from the mouse, this study supports the existence of a CSF1-dependent feedback loop, linking macrophages of the liver with bone marrow and blood monocytes, to mediate homeostatic control of the size of the liver. The results also provide evidence of safety and efficacy for possible clinical applications of CSF1-Fc.",2016 Sep 1,"['Sauter, Kristin A.', 'Waddell, Lindsey A.', 'Lisowski, Zofia M.', 'Young, Rachel', 'Lefevre, Lucas', 'Davis, Gemma M.', 'Clohisey, Sara M.', 'McCulloch, Mary', 'Magowan, Elizabeth', 'Mabbott, Neil A.', 'Summers, Kim M.', 'Hume, David A.']",Am J Physiol Gastrointest Liver Physiol,,,
,PMC,"Multiplexed Molecular Diagnostics for Respiratory, Gastrointestinal, and Central Nervous System Infections",http://dx.doi.org/10.1093/cid/ciw494,PMC5091344,,,"The development and implementation of highly multiplexed molecular diagnostic tests have allowed clinical microbiology laboratories to more rapidly and sensitively detect a variety of pathogens directly in clinical specimens. Current US Food and Drug Administration–approved multiplex panels target multiple different organisms simultaneously and can identify the most common pathogens implicated in respiratory viral, gastrointestinal, or central nervous system infections. This review summarizes the test characteristics of available assays, highlights the advantages and limitations of multiplex technology for infectious diseases, and discusses potential utilization of these new tests in clinical practice.",,"['Hanson, Kimberly E.', 'Couturier, Marc Roger']",,,,
,PMC,New agents modulating the renin-angiotensin-aldosterone system—Will there be a new therapeutic option?,http://dx.doi.org/10.1177/1535370216660211,PMC5068455,,,"The renin-angiotensin-aldosterone system (RAAS) is more complex than it was originally regarded. According to the current subject knowledge, there are two main axes of the RAAS: (1) angiotensin-converting enzyme (ACE)-angiotensin II-AT(1) receptor axis and (2) ACE2-angiotensin-(1-7)-Mas receptor axis. The activation of the first axis leads to deleterious effects, including vasoconstriction, endothelial dysfunction, thrombosis, inflammation, and fibrosis; therefore, blocking the components of this axis is a highly rational and commonly used therapeutic procedure. The ACE2-Ang-(1-7)-Mas receptor axis has a different role, since it often opposes the effects induced by the classical ACE-Ang II-AT(1) axis. Once the positive effects of the ACE2-Ang-(1-7)-Mas axis were discovered, the alternative ways of pharmacotherapy activating this axis of RAAS appeared. This article briefly describes new molecules affecting the RAAS, namely: recombinant human ACE2, ACE2 activators, angiotensin-(1-7) peptide and non-peptide analogs, aldosterone synthase inhibitors, and the third and fourth generation of mineralocorticoid receptor antagonists. The results of the experimental and clinical studies are encouraging, which leads us to believe that these new molecules can support the treatment of cardiovascular diseases as well as cardiometabolic disorders.",,"['Gromotowicz-Poplawska, Anna', 'Szoka, Piotr', 'Kolodziejczyk, Patrycjusz', 'Kramkowski, Karol', 'Wojewodzka-Zelezniakowicz, Marzena', 'Chabielska, Ewa']",,,,
,PMC,Modulation of Host Immunity by the Human Metapneumovirus,http://dx.doi.org/10.1128/CMR.00081-15,PMC5010756,,,"Globally, as a leading agent of acute respiratory tract infections in children <5 years of age and the elderly, the human metapneumovirus (HMPV) has gained considerable attention. As inferred from studies comparing vaccinated and experimentally infected mice, the acquired immune response elicited by this pathogen fails to efficiently clear the virus from the airways, which leads to an exaggerated inflammatory response and lung damage. Furthermore, after disease resolution, there is a poor development of T and B cell immunological memory, which is believed to promote reinfections and viral spread in the community. In this article, we discuss the molecular mechanisms that shape the interactions of HMPV with host tissues that lead to pulmonary pathology and to the development of adaptive immunity that fails to protect against natural infections by this virus.",,"['Céspedes, Pablo F.', 'Palavecino, Christian E.', 'Kalergis, Alexis M.', 'Bueno, Susan M.']",,,,
,PMC,"Regulatory effect of cytokine-induced neutrophil chemoattractant, epithelial neutrophil-activating peptide 78 and pyrrolidine dithiocarbamate on pulmonary neutrophil aggregation mediated by nuclear factor-κB in lipopolysaccharide-induced acute respiratory distress syndrome mice",http://dx.doi.org/10.3892/etm.2016.3520,PMC4998193,,,"In the present study, the regulatory effect of cytokine-induced neutrophil chemoattractant (CINC) and epithelial neutrophil-activating peptide 78 (ENA-78) on pulmonary neutrophil (PMN) accumulation in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) mice, and the therapeutic effect of pyrrolidine dithiocarbamate (PDTC), was investigated. BALB/c mice were divided into control, LPS and PDTC + LPS groups using a random number table. The phosphorylation of nuclear factor-κB (NF-κB) was detected using a western blot, and the mRNA expression levels of CINC were evaluated using reverse transcription-quantitative polymerase chain reaction. The expression of NF-κB, CINC and ENA-78 was detected using immunohistochemistry. The production of interleukin (IL)-8 and IL-10 in serum and broncho-alveolar lavage fluid (BALF) was analyzed using an enzyme-linked immunosorbent assay. The total number of leukocytes and proportion of PMNs in BALF was also determined. Following injection with LPS (20 mg/kg), the expression levels of p-NF-κB, CINC and ENA-78 were increased in lung tissue, and the expression levels of IL-8, IL-10 and the number of PMNs increased in serum and BALF. However, in comparison with the LPS group, the degree of lung injury was reduced in ARDS mice that were treated with PDTC. In addition, the expression level of p-NF-κB and the production of chemokines in lung tissue decreased in ARDS mice that were treated with PDTC, and the number of PMNs in BALF also decreased. In conclusion, the results of the present study suggest that the LPS-induced phosphorylation of NF-κB may result in the synthesis and release of CINC and ENA-78, which induce the accumulation of PMNs in the lung. Therefore, PDTC may be used to reduce the production of chemokines and cytokines, thereby decreasing the activation of PMNs in lung tissue and reducing the damage of lung tissue in ARDS.",,"['Wang, Hongman', 'Zhao, Jiping', 'Xue, Guansheng', 'Wang, Junfei', 'Wu, Jinxiang', 'Wang, Donghui', 'Dong, Liang']",,,,
,PMC,"CCL2, but not its receptor, is essential to restrict immune privileged central nervous system‐invasion of Japanese encephalitis virus via regulating accumulation of CD11b(+) Ly‐6C(hi) monocytes",http://dx.doi.org/10.1111/imm.12626,PMC5011677,,,"Japanese encephalitis virus (JEV) is a re‐emerging zoonotic flavivirus that poses an increasing threat to global health and welfare due to rapid changes in climate and demography. Although the CCR2–CCL2 axis plays an important role in trafficking CD11b(+) Ly‐6C(hi) monocytes to regulate immunopathological diseases, little is known about their role in monocyte trafficking during viral encephalitis caused by JEV infection. Here, we explored the role of CCR2 and its ligand CCL2 in JE caused by JEV infection using CCR2‐ and CCL2‐ablated murine models. Somewhat surprisingly, the ablation of CCR2 and CCL2 resulted in starkly contrasting susceptibility to JE. CCR2 ablation induced enhanced resistance to JE, whereas CCL2 ablation highly increased susceptibility to JE. This contrasting regulation of JE progression by CCR2 and CCL2 was coupled to central nervous system (CNS) infiltration of Ly‐6C(hi) monocytes and Ly‐6G(hi) granulocytes. There was also enhanced expression of CC and CXC chemokines in the CNS of CCL2‐ablated mice, which appeared to induce CNS infiltration of these cell populations. However, our data revealed that contrasting regulation of JE in CCR2‐ and CCL2‐ablated mice was unlikely to be mediated by innate natural killer and adaptive T‐cell responses. Furthermore, CCL2 produced by haematopoietic stem cell‐derived leucocytes played a dominant role in CNS accumulation of Ly‐6C(hi) monocytes in infected bone marrow chimeric models, thereby exacerbating JE progression. Collectively, our data indicate that CCL2 plays an essential role in conferring protection against JE caused by JEV infection. In addition, blockage of CCR2, but not CCL2, will aid in the development of strategies for prophylactics and therapeutics of JE.",,"['Kim, Jin Hyoung', 'Patil, Ajit Mahadev', 'Choi, Jin Young', 'Kim, Seong Bum', 'Uyangaa, Erdenebileg', 'Hossain, Ferdaus Mohd Altaf', 'Park, Sang‐Youel', 'Lee, John Hwa', 'Kim, Koanhoi', 'Eo, Seong Kug']",,,,
,PMC,Standard and AEGIS nicking molecular beacons detect amplicons from the Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1016/j.jviromet.2016.07.008,PMC5010982,,,"This paper combines two advances to detect MERS-CoV, the causative agent of Middle East Respiratory Syndrome, that have emerged over the past few years from the new field of “synthetic biology”. Both are based on an older concept, where molecular beacons are used as the downstream detection of viral RNA in biological mixtures followed by reverse transcription PCR amplification. The first advance exploits the artificially expanded genetic information systems (AEGIS). AEGIS adds nucleotides to the four found in standard DNA and RNA (xNA); AEGIS nucleotides pair orthogonally to the A:T and G:C pairs. Placing AEGIS components in the stems of molecular beacons is shown to lower noise by preventing unwanted stem invasion by adventitious natural xNA. This should improve the signal-to-noise ratio of molecular beacons operating in complex biological mixtures. The second advance introduces a nicking enzyme that allows a single target molecule to activate more than one beacon, allowing “signal amplification”. Combining these technologies in primers with components of a self-avoiding molecular recognition system (SAMRS), we detect 50 copies of MERS-CoV RNA in a multiplexed respiratory virus panel by generating fluorescence signal visible to human eye and/or camera.",,"['Yaren, Ozlem', 'Glushakova, Lyudmyla G.', 'Bradley, Kevin M.', 'Hoshika, Shuichi', 'Benner, Steven A.']",,,,
,PMC,THE EXPANDING REGULATORY NETWORK OF STING-MEDIATED SIGNALING,http://dx.doi.org/10.1016/j.mib.2016.05.014,PMC4983512,,,"The identification and characterization of DNA-sensing pathways has been a subject of intensive investigation for the last decade. This interest, in part, is supported by the fact that the main outcome of DNA-responses is production of type I interferon (IFN-I), which, if produced in excessive amounts, leads to various pathologies. STING (Stimulator of Interferon Genes) is positioned in the center of these responses and is activated either via direct sensing of second messengers or via interaction with upstream sensors of dsDNA. STING mediates responses to pathogens as well as host-derived DNA and is, therefore, linked to various autoimmune diseases, cancer predisposition and ageing. Recent mouse models of DNA damage showed the adaptor STING to be crucial for heightened resting levels of IFN-I. In this review, we will focus on recent advances in understanding the regulation of STING-signaling and identification of its novel components.",,"['Surpris, Guy', 'Poltorak, Alexander']",,,,
,PMC,Identification and Characterization of a Ribose 2′-O-Methyltransferase Encoded by the Ronivirus Branch of Nidovirales,http://dx.doi.org/10.1128/JVI.00658-16,PMC4944298,,,"The order Nidovirales currently comprises four virus families: Arteriviridae, Coronaviridae (divided into the subfamilies Coronavirinae and Torovirinae), Roniviridae, and the recently recognized Mesoniviridae. RNA cap formation and methylation have been best studied for coronaviruses, with emphasis on the identification and characterization of two virus-encoded methyltransferases (MTases) involved in RNA capping, a guanine-N7-MTase and a ribose-2′-O-MTase. Although bioinformatics analyses suggest that these MTases may also be encoded by other nidoviruses with large genomes, such as toroviruses and roniviruses, no experimental evidence has been reported thus far. In this study, we show that a ronivirus, gill-associated virus (GAV), encodes the 2′-O-MTase activity, although we could not detect 2′-O-MTase activity for the homologous protein of a torovirus, equine torovirus, which is more closely related to coronaviruses. Like the coronavirus 2′-O-MTase, the roniviral 2′-O-MTase harbors a catalytic K-D-K-E tetrad that is conserved among 2′-O-MTases and can target only the N7-methylated cap structure of adenylate-primed RNA substrates. However, in contrast with the coronavirus protein, roniviral 2′-O-MTase does not require a protein cofactor for stimulation of its activity and differs in its preference for several biochemical parameters, such as reaction temperature and pH. Furthermore, the ronivirus 2′-O-MTase can be targeted by MTase inhibitors. These results extend our current understanding of nidovirus RNA cap formation and methylation beyond the coronavirus family. IMPORTANCE Methylation of the 5′-cap structure of viral RNAs plays important roles in genome replication and evasion of innate recognition of viral RNAs by cellular sensors. It is known that coronavirus nsp14 acts as an N7-(guanine)-methyltransferase (MTase) and nsp16 as a 2′-O-MTase, which are involved in the modification of RNA cap structure. However, these enzymatic activities have not been shown for any other nidoviruses beyond coronaviruses in the order Nidovirales. In this study, we identified a 2′-O-methyltransferase encoded by ronivirus that shows common and unique features in comparison with that of coronaviruses. Ronivirus 2′-O-MTase does not need a protein cofactor for MTase activity, whereas coronavirus nsp16 needs the stimulating factor nsp10 for its full activity. The conserved K-D-K-E catalytic tetrad is identified in ronivirus 2′-O-MTase. These results extend our understanding of nidovirus RNA capping and methylation beyond coronaviruses and also strengthen the evolutionary and functional links between roniviruses and coronaviruses.",,"['Zeng, Cong', 'Wu, Andong', 'Wang, Yi', 'Xu, Shan', 'Tang, Yingke', 'Jin, Xu', 'Wang, Shilei', 'Qin, Lei', 'Sun, Ying', 'Fan, Chengpeng', 'Snijder, Eric J.', 'Neuman, Benjamin W.', 'Chen, Yu', 'Ahola, Tero', 'Guo, Deyin']",,,,
,PMC,Structural and Biochemical Analyses of Swine Major Histocompatibility Complex Class I Complexes and Prediction of the Epitope Map of Important Influenza A Virus Strains,http://dx.doi.org/10.1128/JVI.00119-16,PMC4944273,,,"The lack of a peptide-swine leukocyte antigen class I (pSLA I) complex structure presents difficulties for the study of swine cytotoxic T lymphocyte (CTL) immunity and molecule vaccine development to eliminate important swine viral diseases, such as influenza A virus (IAV). Here, after cloning and comparing 28 SLA I allelic genes from Chinese Heishan pigs, pSLA-3*hs0202 was crystalized and solved. SLA-3*hs0202 binding with sβ2m and a KMNTQFTAV (hemagglutinin [HA]-KMN9) peptide from the 2009 pandemic swine H1N1 strain clearly displayed two distinct conformations with HA-KMN9 peptides in the structures, which are believed to be beneficial to stimulate a broad spectrum of CTL immune responses. Notably, we found that different HA-KMN9 conformations are caused, not only by the flexibility of the side chains of residues in the peptide-binding groove (PBG), but also by the skewing of α1 and α2 helixes forming the PBG. In addition, alanine scanning and circular-dichroism (CD) spectra confirmed that the B, D, and F pockets play critical biochemical roles in determining the peptide-binding motif of SLA-3*hs0202. Based on biochemical parameters and comparisons to similar pockets in other known major histocompatibility complex class I (MHC-I) structures, the fundamental motif for SLA-3*hs0202 was determined to be X-(M/A/R)-(N/Q/R/F)-X-X-X-X-X-(V/I) by refolding in vitro and multiple mutant peptides. Finally, 28 SLA-3*hs0202-restricted epitope candidates were identified from important IAV strains, and two of them have been found in humans as HLA-A*0201-specific IAV epitopes. Structural and biochemical illumination of pSLA-3*hs0202 can benefit vaccine development to control IAV in swine. IMPORTANCE We crystalized and solved the first SLA-3 structure, SLA-3*hs0202, and found that it could present the same IAV peptide with two distinct conformations. Unlike previous findings showing that variable peptide conformations are caused only by the flexibility of the side chains in the groove, the skewing of the α1 and α2 helixes is important in the different peptide conformations in SLA-3*hs0202. We also determined the fundamental motif for SLA-3*hs0202 to be X-(M/A/R)-(N/Q/R/F)-X-X-X-X-X-(V/I) based on a series of structural and biochemical analyses, and 28 SLA-3*hs0202-restricted epitope candidates were identified from important IAV strains. We believe our structure and analyses of pSLA-3*hs0202 can benefit vaccine development to control IAV in swine.",,"['Fan, Shuhua', 'Wu, Yanan', 'Wang, Song', 'Wang, Zhenbao', 'Jiang, Bo', 'Liu, Yanjie', 'Liang, Ruiying', 'Zhou, Wenzhong', 'Zhang, Nianzhi', 'Xia, Chun']",,,,
,PMC,"Comparative genomics of the human, macaque and mouse major histocompatibility complex",http://dx.doi.org/10.1111/imm.12624,PMC5214800,,,"The MHC is a highly polymorphic genomic region that encodes the transplantation and immune regulatory molecules. It receives special attention for genetic investigation because of its important role in the regulation of innate and adaptive immune responses and its strong association with numerous infectious and/or autoimmune diseases. The MHC locus was first discovered in the mouse and for the past 50 years it has been studied most intensively in both mice and humans. However, in recent years the macaque species have emerged as some of the more important and advanced experimental animal models for biomedical research into MHC with important human immunodeficiency virus/simian immunodeficiency virus and transplantation studies undertaken in association with precise MHC genotyping and haplotyping methods using Sanger sequencing and next‐generation sequencing. Here, in this special issue on ‘Macaque Immunology’ we provide a short review of the genomic similarities and differences among the human, macaque and mouse MHC class I and class II regions, with an emphasis on the association of the macaque class I region with MHC polymorphism, haplotype structure and function.",,"['Shiina, Takashi', 'Blancher, Antoine', 'Inoko, Hidetoshi', 'Kulski, Jerzy K.']",,,,
,PMC,Assembly and release of infectious hepatitis C virus involving unusual organization of the secretory pathway,http://dx.doi.org/10.4254/wjh.v8.i19.796,PMC4937168,,,"AIM: To determine if calnexin (CANX), RAB1 and alpha-tubulin were involved in the production of hepatitis C virus (HCV) particles by baby hamster kidney-West Nile virus (BHK-WNV) cells. METHODS: Using a siRNA-based approach complemented with immuno-fluorescence confocal microscope and Western blot studies, we examined the roles of CANX, RAB1 and alpha-tubulin in the production of HCV particles by permissive BHK-WNV cells expressing HCV structural proteins or the full-length genome of HCV genotype 1a. Immuno-fluorescence studies in producer cells were performed with monoclonal antibodies against HCV structural proteins, as well as immunoglobulin from the serum of a patient recently cured from an HCV infection of same genotype. The cellular compartment stained by the serum immunoglobulin was also observed in thin section transmission electron microscopy. These findings were compared with the JFH-1 strain/Huh-7.5 cell model. RESULTS: We found that CANX was necessary for the production of HCV particles by BHK-WNV cells. This process involved the recruitment of a subset of HCV proteins, detected by immunoglobulin of an HCV-cured patient, in a compartment of rearranged membranes bypassing the endoplasmic reticulum-Golgi intermediary compartment and surrounded by mitochondria. It also involved the maturation of N-linked glycans on HCV envelope proteins, which was required for assembly and/or secretion of HCV particles. The formation of this specialized compartment required RAB1; upon expression of HCV structural genes, this compartment developed large vesicles with viral particles. RAB1 and alpha-tubulin were required for the release of HCV particles. These cellular factors were also involved in the production of HCVcc in the JFH-1 strain/Huh-7.5 cell system, which involves HCV RNA replication. The secretion of HCV particles by BHK-WNV cells presents similarities with a pathway involving caspase-1; a caspase-1 inhibitor was found to suppress the production of HCV particles from a full-length genome. CONCLUSION: Prior activity of the WNV subgenomic replicon in BHK-21 cells promoted re-wiring of host factors for the assembly and release of infectious HCV in a caspase-1-dependent mechanism.",,"['Triyatni, Miriam', 'Berger, Edward A', 'Saunier, Bertrand']",,,,
,PMC,Structure of the sirtuin‐linked macrodomain SAV0325 from Staphylococcus aureus,http://dx.doi.org/10.1002/pro.2974,PMC5338245,,,"Cells use the post‐translational modification ADP‐ribosylation to control a host of biological activities. In some pathogenic bacteria, an operon‐encoded mono‐ADP‐ribosylation cycle mediates response to host‐induced oxidative stress. In this system, reversible mono ADP‐ribosylation of a lipoylated target protein represses oxidative stress response. An NAD(+)‐dependent sirtuin catalyzes the single ADP‐ribose (ADPr) addition, while a linked macrodomain‐containing protein removes the ADPr. Here we report the crystal structure of the sitruin‐linked macrodomain protein from Staphylococcus aureus, SauMacro (also known as SAV0325) to 1.75‐Å resolution. The monomeric SauMacro bears a previously unidentified Zn(2+)‐binding site that putatively aids in substrate recognition and catalysis. An amino‐terminal three‐helix bundle motif unique to this class of macrodomain proteins provides a structural scaffold for the Zn(2+) site. Structural features of the enzyme further indicate a cleft proximal to the Zn(2+) binding site appears well suited for ADPr binding, while a deep hydrophobic channel in the protein core is suitable for binding the lipoate of the lipoylated protein target.",,"['Appel, C. Denise', 'Feld, Geoffrey K.', 'Wallace, Bret D.', 'Williams, R. Scott']",,,,
,PMC,VIRULENCE FACTORS IN PORCINE CORONAVIRUSES AND VACCINE DESIGN,http://dx.doi.org/10.1016/j.virusres.2016.07.003,PMC5159199,,,"Porcine enteric coronaviruses (CoVs) cause severe disease in the porcine herds worldwide, leading to important economic losses. Despite the knowledge of these viruses since the 1970’s, vaccination strategies have not been implemented, leading to continuous re-emergence of novel virulent strains. Live attenuated vaccines historically have been the most efficient. We consider that the new trend is the development of recombinant vaccines by using reverse genetics systems to engineer attenuated viruses, which could be used as effective and safe modified live vaccine candidates. To this end, host cell signaling pathways influencing porcine CoV virulence should be identified. Similarly, the identity of viral proteins involved in the modulation of host cell pathways influencing CoV pathogenesis should be analyzed. With this information, and using reverse genetics systems, it is possible to design viruses with modifications in the viral proteins acting as virulence factors, which may lead to attenuated viruses and, therefore, vaccine candidates. In addition, novel antiviral drugs may be developed once the host cell pathways and the molecular mechanism affecting porcine CoV replication and virulence are known. This review is focused in the host cell responses to enteric porcine CoV infection and the viral proteins involved in pathogenesis.",,"['Zuñiga, Sonia', 'Pascual-Iglesias, Alejandro', 'Sanchez, Carlos M.', 'Sola, Isabel', 'Enjuanes, Luis']",,,,
,PMC,Axonopathy in the Central Nervous System Is the Hallmark of Mice with a Novel Intragenic Null Mutation of Dystonin,http://dx.doi.org/10.1534/genetics.116.186932,PMC5012385,,,"Dystonia musculorum is a neurodegenerative disorder caused by a mutation in the dystonin gene. It has been described in mice and humans where it is called hereditary sensory autonomic neuropathy. Mutated mice show severe movement disorders and die at the age of 3–4 weeks. This study describes the discovery and molecular, clinical, as well as pathological characterization of a new spontaneously occurring mutation in the dystonin gene in C57BL/6N mice. The mutation represents a 40-kb intragenic deletion allele of the dystonin gene on chromosome 1 with exactly defined deletion borders. It was demonstrated by Western blot, mass spectrometry, and immunohistology that mice with a homozygous mutation were entirely devoid of the dystonin protein. Pathomorphological lesions were restricted to the brain stem and spinal cord and consisted of swollen, argyrophilic axons and dilated myelin sheaths in the white matter and, less frequently, total chromatolysis of neurons in the gray matter. Axonal damage was detected by amyloid precursor protein and nonphosphorylated neurofilament immunohistology. Axonopathy in the central nervous system (CNS) represents the hallmark of this disease. Mice with the dystonin mutation also showed suppurative inflammation in the respiratory tract, presumably due to brain stem lesion-associated food aspiration, whereas skeletal muscles showed no pathomorphological changes. This study describes a novel mutation in the dystonin gene in mice leading to axonopathy in the CNS. In further studies, this model may provide new insights into the pathogenesis of neurodegenerative diseases and may elucidate the complex interactions of dystonin with various other cellular proteins especially in the CNS.",,"['Seehusen, Frauke', 'Kiel, Kirsten', 'Jottini, Stefano', 'Wohlsein, Peter', 'Habierski, Andre', 'Seibel, Katharina', 'Vogel, Tanja', 'Urlaub, Henning', 'Kollmar, Martin', 'Baumgärtner, Wolfgang', 'Teichmann, Ulrike']",,,,
,PMC,"Medical intelligence, security and global health: the foundations of a new health agenda",http://dx.doi.org/10.1177/0141076816656483,PMC4941003,,,"Medical intelligence, security and global health are distinct fields that often overlap, especially as the drive towards a global health security agenda gathers pace. Here, we outline some of the ways in which this has happened in the recent past during the recent Ebola epidemic in West Africa and in the killing of Osama Bin laden by US intelligence services. We evaluate medical intelligence and the role it can play in global health security; we also attempt to define a framework that illustrates how medical intelligence can be incorporated into foreign policy action in order delineate the boundaries and scope of this growing field.",,"['Bowsher, G', 'Milner, C', 'Sullivan, R']",,,,
,PMC,Live Virus Vaccines Based on a Vesicular Stomatitis Virus (VSV) Backbone: Standardized Template with Key Considerations for a Risk/Benefit Assessment(),http://dx.doi.org/10.1016/j.vaccine.2016.06.071,PMC5220644,,,,,"['Clarke, David K.', 'Hendry, R. Michael', 'Singh, Vidisha', 'Rose, John K.', 'Seligman, Stephen J.', 'Klug, Bettina', 'Kochhar, Sonali', 'Mac, Lisa Marie', 'Carbery, Baevin', 'Chen, Robert T', None]",,,,
,PMC,Inhibitory Antibodies Targeting Emerging Viruses: Advancements and Mechanisms,http://dx.doi.org/10.1128/CVI.00136-16,PMC4933769,,,"From Ebola virus outbreaks in Western Africa to the introduction of chikungunya and Zika viruses in the Americas, new and neglected viruses continue to emerge and spread around the world. Due to a lack of existing vaccines or specific therapeutics, little other than supportive care and attempts to interrupt transmission can be provided during initial outbreaks. This has prompted a shift in vaccine design and development to identify novel epitopes and mechanisms of protection that may offer a broader range of protection against groups or whole families of viruses. Receptor-binding domains and other motifs within viral envelope proteins represent one excellent opportunity to target communal epitopes shared by related viruses. Similarly, for viruses where envelope participates in driving viral egress from infected cells, shared epitopes need to be identified to guide the development of broadly protective antibodies and vaccines. Here, we discuss recent advances in our understanding of broadly protective humoral responses for emerging viruses.",,"['Jin, Jing', 'Simmons, Graham']",,,,
,PMC,Gentiana scabra Reduces SR-A Expression and Oxidized-LDL Uptake in Human Macrophages,http://dx.doi.org/10.6515/ACS20150416A,PMC4963422,,,"BACKGROUND: Macrophages can imbibe low-density lipoprotein (LDL) through scavenger receptors to become foam cells, which is critical in the initiation and progression of atherosclerosis. Mounting evidence suggests that the anti-inflammatory nature of Chinese herbs have the capacity to halt the complex mechanisms underlying atherosclerosis. This study examined the effects of Chinese herbs on foam cell formation. METHODS: Chinese herbs were obtained from the Sun Ten pharmaceutic company. Using oxidized LDL (OxLDL) uptake and a cell toxicity assay, we screened more than 30 types of Chinese herbs. Western blotting was used to determine expressions of scavenger receptors (SRs) and extracellular-signal-regulated kinase (ERK) activities. RESULTS: We found that Gentiana scabra reduced oxidized LDL uptake effectively in THP-1 macrophages (p < 0.05 vs. OxLDL treated control). Moreover, treatment with Gentiana scabra in THP-1 macrophages resulted in decreased expression of scavenger receptor- A (SR-A) (p < 0.05 vs. control). Molecular investigation revealed that Gentiana scabra inhibited SR-A protein expression, possibly by regulating ERK signaling pathways (p < 0.05 vs. control). CONCLUSIONS: By regulating SR-A expression, Gentiana scabra reduced oxidized LDL uptake in human macrophages. These results support the potential use of Gentiana scabra in treating atherosclerosis.",,"['Lin, Chin-Sheng', 'Liu, Pang-Yen', 'Lian, Chen-Hao', 'Lin, Ching-Heng', 'Lai, Jenn-Haung', 'Ho, Ling-Jun', 'Yang, Shih-Ping', 'Cheng, Shu-Meng']",,,,
,PMC,Health Care Visits as a Risk Factor for Tuberculosis in Taiwan: A Population-Based Case–Control Study,http://dx.doi.org/10.2105/AJPH.2016.303152,PMC4984759,,,"Objectives. To assess whether health care visits of nontuberculous patients are a risk factor for contracting tuberculosis. Methods. We conducted a case–control study nested within the cohort of 1 million individuals from the health insurance database in Taiwan between 2003 and 2010. We identified incident cases of tuberculosis through International Classification of Diseases, Ninth Revision (ICD-9) codes and prescription of antituberculosis drugs. We identified 4202 case participants and 16 808 control participants matched by age, gender, and date of diagnosis to estimate the association between frequency of health care visits and incidence of tuberculosis. Results. Frequency of health care visits was associated with increased risk of tuberculosis in a dose-dependent manner after adjustment for other medical comorbidities (P for trend < .001). Compared with individuals with fewer than 5 visits per year, those with more than 30 had a 77% increase in tuberculosis risk (adjusted odds ratio = 1.77; 95% confidence interval [CI] = 1.60, 1.97). Conclusions. Frequent health care visits of nontuberculous patients appear to be a risk factor for contracting tuberculosis. Public Health Implications. Efforts should focus on educating the general population to avoid unnecessary hospital visits, strengthening active case finding, and intensifying infection control in all health care settings.",,"['Pan, Sung-Ching', 'Chen, Chien-Chou', 'Chiang, Yi-Ting', 'Chang, Hsing-Yi', 'Fang, Chi-Tai', 'Lin, Hsien-Ho']",,,,
,PMC,Association of human leukocyte antigen class II alleles with severe Middle East respiratory syndrome-coronavirus infection,http://dx.doi.org/10.4103/1817-1737.185756,PMC4966224,27512511,CC BY-NC-SA,"BACKGROUND: Middle East Respiratory Syndrome (MERS) is a disease of the lower respiratory tract and is characterized by high mortality. It is caused by a beta coronavirus (CoV) referred to as MERS-CoV. Majority of MERS-CoV cases have been reported from Saudi Arabia. AIM: We investigated the human leukocyte antigen (HLA) Class II alleles in patients with severe MERS who were admitted in our Intensive Care Unit. METHODS: A total of 23 Saudi patients with severe MERS-CoV infection were typed for HLA class II, results were compared with those of 161 healthy controls. RESULTS: Two HLA class II alleles were associated with the disease; HLA-DRB1*11:01 and DQB1*02:02, but not with the disease outcome. CONCLUSIONS: Our results suggest that the HLA-DRB1*11:01 and DQB1*02:02 may be associated with susceptibility to MERS.",2016 Jul-Sep,"['Hajeer, Ali H.', 'Balkhy, Hanan', 'Johani, Sameera', 'Yousef, Mohammed Z.', 'Arabi, Yaseen']",Ann Thorac Med,,,
,PMC,Health Technology Assessment of pathogen reduction technologies applied to plasma for clinical use,http://dx.doi.org/10.2450/2016.0065-16,PMC4942318,,,"Although existing clinical evidence shows that the transfusion of blood components is becoming increasingly safe, the risk of transmission of known and unknown pathogens, new pathogens or re-emerging pathogens still persists. Pathogen reduction technologies may offer a new approach to increase blood safety. The study is the output of collaboration between the Italian National Blood Centre and the Post-Graduate School of Health Economics and Management, Catholic University of the Sacred Heart, Rome, Italy. A large, multidisciplinary team was created and divided into six groups, each of which addressed one or more HTA domains. Plasma treated with amotosalen + UV light, riboflavin + UV light, methylene blue or a solvent/detergent process was compared to fresh-frozen plasma with regards to current use, technical features, effectiveness, safety, economic and organisational impact, and ethical, social and legal implications. The available evidence is not sufficient to state which of the techniques compared is superior in terms of efficacy, safety and cost-effectiveness. Evidence on efficacy is only available for the solvent/detergent method, which proved to be non-inferior to untreated fresh-frozen plasma in the treatment of a wide range of congenital and acquired bleeding disorders. With regards to safety, the solvent/detergent technique apparently has the most favourable risk-benefit profile. Further research is needed to provide a comprehensive overview of the cost-effectiveness profile of the different pathogen-reduction techniques. The wide heterogeneity of results and the lack of comparative evidence are reasons why more comparative studies need to be performed.",,"['Cicchetti, Americo', 'Berrino, Alexandra', 'Casini, Marina', 'Codella, Paola', 'Facco, Giuseppina', 'Fiore, Alessandra', 'Marano, Giuseppe', 'Marchetti, Marco', 'Midolo, Emanuela', 'Minacori, Roberta', 'Refolo, Pietro', 'Romano, Federica', 'Ruggeri, Matteo', 'Sacchini, Dario', 'Spagnolo, Antonio G.', 'Urbina, Irene', 'Vaglio, Stefania', 'Grazzini, Giuliano', 'Liumbruno, Giancarlo M.']",,,,
,PMC,Effects of the −791(C→T) mutation in the promoter for tumor necrosis factor alpha on gene expression and resistance of Large White pigs to enterotoxigenic Escherichia coli F18,,PMC4924554,,,"Tumor necrosis factor alpha (TNF-α) plays an important role in the immune system. In this study, TNF-α expression was analyzed in 11 tissues of 8 piglets resistant to enterotoxigenic Escherichia coli (ETEC) F18 and 8 ETEC F18-susceptible piglets from the Large White breed. The expression levels of TNF-α were high in immune organs (spleen, lung, thymus, and lymph nodes). The levels were higher in ETEC F18-resistant piglets than in ETEC F18-susceptible piglets, with significant differences in spleen, kidney, thymus, lymph node, and duodenum (P < 0.05). The mutation TNF-α −791(C→T) and 3 genotypes (CC, CT, and TT) were identified. The TNF-α expression levels in the spleen, kidney, lymph nodes, and duodenum were significantly higher in the TT pigs than in the CC pigs (P < 0.05). Thus, TNF-α −791(C→T) has significant effects on mRNA expression and may regulate ETEC F18 resistance of weaning piglets. Therefore, the −791(C→T) mutation of the TNF-α gene could be considered an important potential genetic marker of ETEC F18 resistance.",,"['Liu, Ying', 'Dai, Chaohui', 'Sun, Li', 'Zhu, Guoqiang', 'Wu, Shenglong', 'Bao, Wenbin']",,,,
,PMC,Reinfection of adult cattle with rotavirus B during repeated outbreaks of epidemic diarrhea,,PMC4924552,,,"Rotavirus B (RVB) infection in cattle is poorly understood. The objective of this study was to describe the epidemiological features of repeated outbreaks of epidemic diarrhea due to RVB infection in adult cattle on a large dairy farm complex in Japan. In October 2002, approximately 550 adult cows and approximately 450 in February 2005 had acute watery diarrhea at several farms on the complex. Four months before the first outbreak, RVB antibody-positive rates at subsequently affected farms were significantly lower than at non-affected farms (30% to 32% versus 61% to 67%). During the acute phase of both outbreaks, RVB antibody-positive rates in diarrheal cows tested were as low as 15% to 26%. Most of the farms affected in the second outbreak were also involved in the first outbreak. Some adult cows with RVB diarrhea in the first outbreak showed not only RVB seroresponse, but also RVB shedding in the second outbreak, although none of these cows developed diarrhea. Nucleotide sequences of the VP7 and VP4 genes revealed a close relationship between RVB strains in both outbreaks. Taken together, these results indicate that outbreaks of epidemic RVB diarrhea in adult cows might be influenced by herd immunity and could occur repeatedly at the same farms over several years. To our knowledge, this is the first report on repeated RVB infections in the same cattle.",,"['Hayashi, Michiko', 'Murakami, Toshiaki', 'Kuroda, Yoshizumi', 'Takai, Hikaru', 'Ide, Hisahiro', 'Awang, Ainani', 'Suzuki, Tohru', 'Miyazaki, Ayako', 'Nagai, Makoto', 'Tsunemitsu, Hiroshi']",,,,
,PMC,Infectious Chronic Rhinosinusitis,http://dx.doi.org/10.1016/j.jaip.2016.04.008,PMC4939240,,,"Chronic rhinosinusitis (CRS) is a persistent inflammatory disease that affects a multitude of people worldwide. The pathogenesis of CRS involves many factors including genetics, status of the sinonasal microbiome, infections and environmental influences. Comorbidities associated with CRS include asthma, allergic rhinitis, bronchiectasis and certain kinds of immunodeficiency. CRS can be divided into different subtypes based on endotypes and phenotypes. Infectious CRS is one such category. The etiology of infectious CRS is usually secondary to chronic bacterial infection which commonly begins with a viral upper respiratory tract infection. Humoral antibody deficiencies can underlie difficult-to-treat or recurrent CRS. Infectious CRS can be treated with antimicrobials, topical or oral corticosteroids and nasal saline irrigations. Patients with CRS and humoral immunodeficiency may require an aggressive treatment approach including immunoglobulin replacement therapy. Despite advancements in the field of CRS, targeted therapies and reliable biomarkers are still lacking.",,"['Bose, Sumit', 'Grammer, Leslie C.', 'Peters, Anju T.']",,,,
,PMC,Zika virus: An overview,http://dx.doi.org/10.4103/2249-4863.197256,PMC5290753,28217576,CC BY-NC-SA,"The Zika virus has been in the news for quite some time due to the ongoing recent outbreak in the Southern America, which started in December 2015. It has been declared a public health emergency by the World Health Organization in February 2016 owing to its association with the congenital deformities, particularly microcephaly in infants borne to the infected mothers. The rapid spread of the virus throughout the United States of America and subsequently to Asia has raised serious international concerns. Its spread to countries neighboring India is a serious threat to the Indian population. This review article gives an overview about the virus, its diagnosis, clinical features, and the management.",2016 Jul-Sep,"['Rawal, Gautam', 'Yadav, Sankalp', 'Kumar, Raj']",J Family Med Prim Care,,,
,PMC,The cohort effect in childhood disease dynamics,http://dx.doi.org/10.1098/rsif.2016.0156,PMC4971216,,,"The structure of school terms is well known to influence seasonality of transmission rates of childhood infectious diseases in industrialized countries. A less well-studied aspect of school calendars that influences disease dynamics is that all children enter school on the same day each year. Rather than a continuous inflow, there is a sudden increase in the number of susceptible individuals in schools at the start of the school year. Based on the standard susceptible–exposed–infectious–recovered (SEIR) model, we show that school cohort entry alone is sufficient to generate a biennial epidemic pattern, similar to many observed time series of measles incidence. In addition, cohort entry causes an annual decline in the effective transmission that is evident in observed time series, but not in models without the cohort effect. Including both cohort entry and school terms yields a model fit that is significantly closer to observed measles data than is obtained with either cohort entry or school terms alone (and just as good as that obtained with Schenzle's realistic age-structured model). Nevertheless, we find that the bifurcation structure of the periodically forced SEIR model is nearly identical, regardless of whether forcing arises from cohort entry, school terms and any combination of the two. Thus, while detailed time-series fits are substantially improved by including both cohort entry and school terms, the overall qualitative dynamic structure of the SEIR model appears to be insensitive to the origin of periodic forcing.",,"['He, Daihai', 'Earn, David J. D.']",,,,
,PMC,"Tracing Airline Travelers for a Public Health Investigation: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection in the United States, 2014",,PMC4937116,,,"OBJECTIVE: CDC routinely conducts contact investigations involving travelers on commercial conveyances, such as aircrafts, cargo vessels, and cruise ships. METHODS: The agency used established systems of communication and partnerships with other federal agencies to quickly provide accurate traveler contact information to states and jurisdictions to alert contacts of potential exposure to two travelers with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) who had entered the United States on commercial flights in April and May 2014. RESULTS: Applying the same process used to trace and notify travelers during routine investigations, such as those for tuberculosis or measles, CDC was able to notify most travelers of their potential exposure to MERS-CoV during the first few days of each investigation. CONCLUSION: To prevent the introduction and spread of newly emerging infectious diseases, travelers need to be located and contacted quickly.",,"['Regan, Joanna J.', 'Jungerman, M. Robynne', 'Lippold, Susan A.', 'Washburn, Faith', 'Roland, Efrosini', 'Objio, Tina', 'Schembri, Christopher', 'Gulati, Reena', 'Edelson, Paul J.', 'Alvarado-Ramy, Francisco', 'Pesik, Nicki', 'Cohen, Nicole J.']",,,,
,PMC,A Message from the Editor,,PMC4937107,,,,,,,,,
,PMC,Allosteric Activation of Ubiquitin-Specific Proteases by β-propeller Proteins UAF1 and WDR20,http://dx.doi.org/10.1016/j.molcel.2016.05.031,PMC4958508,,,"Ubiquitin-specific proteases (USPs) constitute the largest family of deubiquitinating enzymes, whose catalytic competency is often modulated by their binding partners through unknown mechanisms. Here we report a series of crystallographic and biochemical analyses of an evolutionarily conserved deubiquitinase, USP12, which is activated by two β-propeller proteins, UAF1 and WDR20. Our structures reveal that UAF1 and WDR20 interact with USP12 at two distinct sites far away from its catalytic center. Without increasing substrate affinity of USP12, the two β-propeller proteins potentiate the enzyme through different allosteric mechanisms. UAF1 docks at the distal end of the USP12 Fingers domain and induces a cascade of structural changes that reach to a critical ubiquitin-contacting loop adjacent to the catalytic cleft. By contrast, WDR20 anchors at the base of this loop and remotely modulates the catalytic center of the enzyme. Our results provide a mechanistic example for allosteric activation of USPs by their regulatory partners.",,"['Li, Heng', 'Lim, Kah Suan', 'Kim, Hyungjin', 'Hinds, Thomas R.', 'Jo, Ukhyun', 'Mao, Haibin', 'Weller, Caroline E.', 'Sun, Ji', 'Chatterjee, Champak', 'D’Andrea, Alan D.', 'Zheng, Ning']",,,,
,PMC,A Human Lectin Microarray for Sperm Surface Glycosylation Analysis,http://dx.doi.org/10.1074/mcp.M116.059311,PMC5013302,,,"Glycosylation is one of the most abundant and functionally important protein post-translational modifications. As such, technology for efficient glycosylation analysis is in high demand. Lectin microarrays are a powerful tool for such investigations and have been successfully applied for a variety of glycobiological studies. However, most of the current lectin microarrays are primarily constructed from plant lectins, which are not well suited for studies of human glycosylation because of the extreme complexity of human glycans. Herein, we constructed a human lectin microarray with 60 human lectin and lectin-like proteins. All of the lectins and lectin-like proteins were purified from yeast, and most showed binding to human glycans. To demonstrate the applicability of the human lectin microarray, human sperm were probed on the microarray and strong bindings were observed for several lectins, including galectin-1, 7, 8, GalNAc-T6, and ERGIC-53 (LMAN1). These bindings were validated by flow cytometry and fluorescence immunostaining. Further, mass spectrometry analysis showed that galectin-1 binds several membrane-associated proteins including heat shock protein 90. Finally, functional assays showed that binding of galectin-8 could significantly enhance the acrosome reaction within human sperms. To our knowledge, this is the first construction of a human lectin microarray, and we anticipate it will find wide use for a range of human or mammalian studies, alone or in combination with plant lectin microarrays.",,"['Sun, Yangyang', 'Cheng, Li', 'Gu, Yihua', 'Xin, Aijie', 'Wu, Bin', 'Zhou, Shumin', 'Guo, Shujuan', 'Liu, Yin', 'Diao, Hua', 'Shi, Huijuan', 'Wang, Guangyu', 'Tao, Sheng-ce']",,,,
,PMC,Antisense Antimicrobial Therapeutics,http://dx.doi.org/10.1016/j.mib.2016.05.017,PMC5069135,,,"Antisense antimicrobial therapeutics are synthetic oligomers that silence expression of specific genes. This specificity confers an advantage over broad-spectrum antibiotics by avoiding unintended effects on commensal bacteria. The sequence-specificity and short length of antisense antimicrobials also pose little risk to human gene expression. Because antisense antimicrobials are a platform technology, they can be rapidly designed and synthesized to target almost any microbe. This reduces drug discovery time, and provides flexibility and a rational approach to drug development. Recent work has shown that antisense technology has the potential to address the antibiotic-resistance crisis, since resistance mechanisms for standard antibiotics apparently have no effect on antisense antimicrobials. Here, we describe current reports of antisense antimicrobials targeted against viruses, parasites, and bacteria.",,"['Sully, Erin K.', 'Geller, Bruce L.']",,,,
,PMC,Middle East Respiratory Syndrome Coronavirus Infection During Pregnancy: A Report of 5 Cases From Saudi Arabia,http://dx.doi.org/10.1093/cid/ciw412,PMC5812010,,,"Little is known about the effects of Middle East respiratory syndrome coronavirus (MERS-CoV) during pregnancy. In Saudi Arabia, 5 cases of MERS-CoV infection among pregnant women were reviewed, and all cases resulted in adverse outcomes. MERS-CoV infection during pregnancy may be associated with maternal and perinatal disease and death.",,"['Assiri, Abdullah', 'Abedi, Glen R.', 'Al Masri, Malak', 'Saeed, Abdulaziz Bin', 'Gerber, Susan I.', 'Watson, John T.']",,,,
,PMC,Avoiding hepatic metastasis naturally: Lessons from the cotton top tamarin (Saguinus oedipus),http://dx.doi.org/10.3748/wjg.v22.i24.5479,PMC4917608,,,"Much has been written about hepatic metastasis and animal models abound. In terms of the human experience, progress in treating this final common pathway, a terminal event of many human malignancies has been relatively slow. The current thinking is that primary prevention is best served by early detection of cancer and eradication of early stage cancers by screening. Some cancers spread early in their course and the role of screening may be limited. Until relatively recently there has not been a pathfinder model that makes the evasion of this unfortunate event a reality. This review discusses such an animal model and attempts to relate it to human disease in terms of intervention. Concrete proposals are also offered on how scientists may be able to intervene to prevent this deadly progression of the cancer process.",,"['Tobi, Martin', 'Thomas, Peter', 'Ezekwudo, Daniel']",,,,
,PMC,Socio-demographic Predictors for Urban Community Disaster Health Risk Perception and Household Based Preparedness in a Chinese Urban City,http://dx.doi.org/10.1371/currents.dis.287fb7fee6f9f4521af441a236c2d519,PMC5569964,28856059,CC BY,"Objectives: There is limited evidence on urban Asian communities' disaster risk perceptions and household level preparedness. Hong Kong is characterized by high population density, and is susceptible to large-scale natural disasters and health crises such as typhoons, fires and infectious disease outbreaks. This research paper investigates the rates and predictors of urban community disaster risk perception, awareness and preparedness, at individual and household levels. Methods: A randomized cross-sectional, population-based telephone survey study was conducted among the Cantonese-speaking population aged over 15 years in Hong Kong. Descriptive statistics were reported. A stepwise multivariate logistic regression analysis was conducted to determine the independent associations between risk perceptions, socioeconomic factors, household characteristics, and personal background. Findings: Final study sample comprised of 1002 respondents with a 63% response rate. The majority of respondents (82.3%) did not perceive Hong Kong as a disaster-susceptible city. Half (54.6%) reported beliefs that the local population had lower disaster awareness than other global cities. Infectious disease outbreak (72.4%), typhoon (12.6%), and fire (7.1%) were ranked as the most-likely-to-occur population-based disasters. Although over 77% believed that basic first aid training was necessary for improving individual disaster preparedness, only a quarter (26.1%) of respondents reported participation in training. Conclusion: Despite Hong Kong’s high level of risk, general public perceptions of disaster in Hong Kong were low, and little preparedness has occurred at the individual or household levels. This report has potential to inform the development of related policies and risk communication strategies in Asian urban cities.",2016 Jun 27,"['Chan, Emily YY', 'Yue, Janice', 'Lee, Poyi', 'Wang, Susan Shuxin']",PLoS Curr,,,
,PMC,Clinical Evaluation of the New High-Throughput Luminex NxTAG Respiratory Pathogen Panel Assay for Multiplex Respiratory Pathogen Detection,http://dx.doi.org/10.1128/JCM.00517-16,PMC4922091,,,"A broad range of viral and bacterial pathogens can cause acute respiratory tract infection. For rapid detection of a broad respiratory pathogen spectrum, multiplex real-time PCR is ideal. This study evaluated the performance of the new Luminex NxTAG Respiratory Pathogen Panel (NxTAG-RPP) in comparison with the BioFire FilmArray Respiratory Panel (FA-RP) or singleplex real-time PCR as reference. A total of 284 clinical respiratory specimens and 3 influenza A/H7N9 viral culture samples were tested. All clinical specimens were processed and analyzed in parallel using NxTAG-RPP and the reference standard method. The H7N9 viral culture samples were tested using NxTAG-RPP only. Overall, the NxTAG-RPP demonstrated ≥93% sensitivity and specificity for all respiratory targets except human coronavirus OC43 (HCoV-OC43) and HCoV-HKU1. The H7N9 virus was detected by the influenza A virus matrix gene target, while other influenza A virus subtyping gene targets in the panel remained negative. Complete concordance between NxTAG-RPP and FA-RP was observed in 98.8% (318/322) of positive results (kappa = 0.92). Substantial agreement was found for most respiratory targets, but significant differences were observed in human metapneumovirus (P = 0.001) and parainfluenza virus type 3 (P = 0.031). NxTAG-RPP has a higher sample throughput than FA-RP (96 samples versus 1 sample per run) while the turnaround times for NxTAG-RPP and FA-RP were 5 h (up to 96 samples) and 1 h (for one sample), respectively. Overall, NxTAG-RPP demonstrated good diagnostic performance for most respiratory pathogens. The high sample throughput with reasonable turnaround time of this new assay makes it a suitable multiplex platform for routine screening of respiratory specimens in hospital-based laboratories.",,"['Chen, Jonathan H. K.', 'Lam, Ho-Yin', 'Yip, Cyril C. Y.', 'Wong, Sally C. Y.', 'Chan, Jasper F. W.', 'Ma, Edmond S. K.', 'Cheng, Vincent C. C.', 'Tang, Bone S. F.', 'Yuen, Kwok-Yung']",,,,
,PMC,"Bat Severe Acute Respiratory Syndrome-Like Coronavirus WIV1 Encodes an Extra Accessory Protein, ORFX, Involved in Modulation of the Host Immune Response",http://dx.doi.org/10.1128/JVI.03079-15,PMC4936131,,,"Bats harbor severe acute respiratory syndrome (SARS)-like coronaviruses (SL-CoVs) from which the causative agent of the 2002-2003 SARS pandemic is thought to have originated. However, despite the fact that a large number of genetically diverse SL-CoV sequences have been detected in bats, only two strains (named WIV1 and WIV16) have been successfully cultured in vitro. These two strains differ from SARS-CoV only in containing an extra open reading frame (ORF) (named ORFX), between ORF6 and ORF7, which has no homology to any known protein sequences. In this study, we constructed a full-length cDNA clone of SL-CoV WIV1 (rWIV1), an ORFX deletion mutant (rWIV1-ΔX), and a green fluorescent protein (GFP)-expressing mutant (rWIV1-GFP-ΔX). Northern blotting and fluorescence microscopy indicate that ORFX was expressed during WIV1 infection. A virus infection assay showed that rWIV1-ΔX replicated as efficiently as rWIV1 in Vero E6, Calu-3, and HeLa-hACE2 cells. Further study showed that ORFX could inhibit interferon production and activate NF-κB. Our results demonstrate for the first time that the unique ORFX in the WIV1 strain is a functional gene involving modulation of the host immune response but is not essential for in vitro viral replication. IMPORTANCE Bats harbor genetically diverse SARS-like coronaviruses (SL-CoVs), and some of them have the potential for interspecies transmission. A unique open reading frame (ORFX) was identified in the genomes of two recently isolated bat SL-CoV strains (WIV1 and -16). It will therefore be critical to clarify whether and how this protein contributes to virulence during viral infection. Here we revealed that the unique ORFX is a functional gene that is involved in the modulation of the host immune response but is not essential for in vitro viral replication. Our results provide important information for further exploration of the ORFX function in the future. Moreover, the reverse genetics system we constructed will be helpful for study of the pathogenesis of this group of viruses and to develop therapeutics for future control of emerging SARS-like infections.",,"['Zeng, Lei-Ping', 'Gao, Yu-Tao', 'Ge, Xing-Yi', 'Zhang, Qian', 'Peng, Cheng', 'Yang, Xing-Lou', 'Tan, Bing', 'Chen, Jing', 'Chmura, Aleksei A.', 'Daszak, Peter', 'Shi, Zheng-Li']",,,,
,PMC,Structural basis of viral RNA-dependent RNA polymerase catalysis and translocation,http://dx.doi.org/10.1073/pnas.1602591113,PMC4948327,,,"Viral RNA-dependent RNA polymerases (RdRPs) play essential roles in viral genome replication and transcription. We previously reported several structural states of the poliovirus RdRP nucleotide addition cycle (NAC) that revealed a unique palm domain-based active site closure mechanism and proposed a six-state NAC model including a hypothetical state representing translocation intermediates. Using the RdRP from another human enterovirus, enterovirus 71, here we report seven RdRP elongation complex structures derived from a crystal lattice that allows three NAC events. These structures suggested a key order of events in initial NTP binding and NTP-induced active site closure and revealed a bona fide translocation intermediate featuring asymmetric movement of the template–product duplex. Our work provides essential missing links in understanding NTP recognition and translocation mechanisms in viral RdRPs and emphasizes the uniqueness of the viral RdRPs compared with other processive polymerases.",,"['Shu, Bo', 'Gong, Peng']",,,,
,PMC,Unique Safety Issues Associated with Virus Vectored Vaccines: Potential for and Theoretical Consequences of Recombination with Wild Type Virus Strains,http://dx.doi.org/10.1016/j.vaccine.2016.04.060,PMC5204448,,,"In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains.",,"['Condit, Richard C.', 'Williamson, Anna-Lise', 'Sheets, Rebecca', 'Seligman, Stephen J.', 'Monath, Thomas P.', 'Excler, Jean-Louis', 'Gurwith, Marc', 'Bok, Karin', 'Robertson, James S.', 'Kim, Denny', 'Hendry, Michael', 'Singh, Vidisha', 'Mac, Lisa M.', 'Chen, Robert T.', None]",,,,
,PMC,Human Phase 1 trial of low-dose inactivated seasonal influenza vaccine formulated with Advax™ delta inulin adjuvant,http://dx.doi.org/10.1016/j.vaccine.2016.05.071,PMC4949042,,,"Influenza vaccines are usually non-adjuvanted but addition of adjuvant may improve immunogenicity and permit dose-sparing, critical for vaccine supply in the event of an influenza pandemic. The aim of this first-in-man study was to determine the effect of delta inulin adjuvant on the safety and immunogenicity of a reduced dose seasonal influenza vaccine. Healthy male and female adults aged 18–65 years were recruited to participate in a randomized controlled study to compare the safety, tolerability and immunogenicity of a reduced-dose 2007 Southern Hemisphere trivalent inactivated influenza vaccine formulated with Advax™ delta inulin adjuvant (LTIV + Adj) when compared to a full-dose of the standard TIV vaccine which does not contain an adjuvant. LTIV + Adj provided equivalent immunogenicity to standard TIV vaccine as assessed by hemagglutination inhibition (HI) assays against each vaccine strain as well as against a number of heterosubtypic strains. HI responses were sustained at 3 months post-immunisation in both groups. Antibody landscapes against a large panel of H3N2 influenza viruses showed distinct age effects whereby subjects over 40 years old had a bimodal baseline HI distribution pattern, with the highest HI titers against the very oldest H3N2 isolates and with a second HI peak against influenza isolates from the last 5–10 years. By contrast, subjects >40 years had a unimodal baseline HI distribution with peak recognition of H3N2 isolates from approximately 20 years ago. The reduced dose TIV vaccine containing Advax adjuvant was well tolerated and no safety issues were identified. Hence, delta inulin may be a useful adjuvant for use in seasonal or pandemic influenza vaccines. Australia New Zealand Clinical Trial Registry: ACTRN12607000599471",,"['Gordon, David L.', 'Sajkov, Dimitar', 'Honda-Okubo, Yoshikazu', 'Wilks, Samuel H.', 'Aban, Malet', 'Barr, Ian G.', 'Petrovsky, Nikolai']",,,,
,PMC,Setting a trap for respiratory viruses,http://dx.doi.org/10.1080/21505594.2016.1204062,PMC5029299,,,,,"Karlsson, Erik A.",,,,
,PMC,Anti-infective Activity of 2-Cyano-3-Acrylamide Inhibitors with Improved Drug-Like Properties against Two Intracellular Pathogens,http://dx.doi.org/10.1128/AAC.03021-15,PMC4914689,,,"Due to the rise of antibiotic resistance and the small number of effective antiviral drugs, new approaches for treating infectious diseases are urgently needed. Identifying targets for host-based therapies represents an emerging strategy for drug discovery. The ubiquitin-proteasome system is a central mode of signaling in the eukaryotic cell and may be a promising target for therapies that bolster the host's ability to control infection. Deubiquitinase (DUB) enzymes are key regulators of the host inflammatory response, and we previously demonstrated that a selective DUB inhibitor and its derivative promote anti-infective activities in host cells. To find compounds with anti-infective efficacy but improved toxicity profiles, we tested a library of predominantly 2-cyano-3-acrylamide small-molecule DUB inhibitors for anti-infective activity in macrophages against two intracellular pathogens: murine norovirus (MNV) and Listeria monocytogenes. We identified compound C6, which inhibited DUB activity in human and murine cells and reduced intracellular replication of both pathogens with minimal toxicity in cell culture. Treatment with C6 did not significantly affect the ability of macrophages to internalize virus, suggesting that the anti-infective activity interferes with postentry stages of the MNV life cycle. Metabolic stability and pharmacokinetic assays showed that C6 has a half-life in mouse liver microsomes of ∼20 min and has a half-life of approximately 4 h in mice when administered intravenously. Our results provide a framework for targeting the host ubiquitin system in the development of host-based therapies for infectious disease. Compound C6 represents a promising tool with which to elucidate the role of DUBs in the macrophage response to infection.",,"['Passalacqua, Karla D.', 'Charbonneau, Marie-Eve', 'Donato, Nicholas J.', 'Showalter, Hollis D.', 'Sun, Duxin', 'Wen, Bo', 'He, Miao', 'Sun, Hanshi', ""O'Riordan, Mary X. D."", 'Wobus, Christiane E.']",,,,
,PMC,"The Assessment, Evaluation, and Management of the Critically Ill Child When Resources are Limited—Southeast Asian Perspective",http://dx.doi.org/10.1055/s-0036-1584672,PMC6260260,,,"The Southeast Asia region comprises 10 independent countries with highly divergent health systems and health status. The heterogeneity in infant and child mortality rates suggests that there is still scope for improvement in the care of critically ill children. There is, however, a paucity of published data on outcomes and processes of care that could affect planning and implementation of intervention programs. Significant challenges in the delivery of care for the critically ill child remain, especially in pre-hospital and in-hospital triaging and emergency care and inpatient hospital care. Potential areas for continued improvement include strengthening of health systems through sustained commitment by local governments, capacity building, and sharing of research output. Simple, low cost, locally available, and effective solutions should be sought. The introduction of standards and auditing tools can assist in determining effectiveness and outcomes of intervention packages that are adapted to local settings. Recognition and acknowledgment of shortfalls between expectations and outcomes is a first step to overcoming some of these obstacles necessary to achieve a seamless interface among pre-hospital, emergency, inpatient, and critical care delivery processes that would improve survival of critically ill children in this region.",,"['Tang, Swee Fong', 'Lum, Lucy']",,,,
,PMC,Antiviral Targets of Human Noroviruses,http://dx.doi.org/10.1016/j.coviro.2016.06.002,PMC4983487,,,"Human noroviruses are major causative agents of sporadic and epidemic gastroenteritis both in children and adults. Currently there are no licensed therapeutic intervention measures either in terms of vaccines or drugs available for these highly contagious human pathogens. Genetic and antigenic diversity of these viruses, rapid emergence of new strains, and their ability to infect a broad population by using polymorphic histo-blood group antigens for cell attachment, pose significant challenges for the development of effective antiviral agents. Despite these impediments, there is progress in the design and development of therapeutic agents. These include capsid-based candidate vaccines, and potential antivirals either in the form of glycomimetics or designer antibodies that block HBGA binding, as well as those that target essential non-structural proteins such as the viral protease and RNA-dependent RNA polymerase. In addition to these classical approaches, recent studies suggest the possibility of interferons and targeting host cell factors as viable approaches to counter norovirus infection. This review provides a brief overview of this progress.",,"['Venkataram Prasad, B. V.', 'Shanker, Sreejesh', 'Muhaxhiri, Zana', 'Deng, Lisheng', 'Choi, Jae-Mun', 'Estes, Mary K.', 'Song, Yongcheng', 'Palzkill, Timothy', 'Atmar, Robert L.']",,,,
,PMC,"POLD1: central mediator of DNA replication and repair, and implication in cancer and other pathologies",http://dx.doi.org/10.1016/j.gene.2016.06.031,PMC4969162,,,"The evolutionarily conserved human polymerase delta (POLD1) gene encodes the large p125 subunit which provides the essential catalytic activities of polymerase δ (Polδ), mediated by 5’–3’ DNA polymerase and 3’–5’ exonuclease moieties. POLD1 associates with three smaller subunits (POLD2, POLD3, POLD4), which together with Replication Factor C and Proliferating Nuclear Cell Antigen constitute the polymerase holoenzyme. Polδ function is essential for replication, with a primary role as the replicase for the lagging strand. Polδ also has an important proofreading ability conferred by the exonuclease activity, which is critical for ensuring replicative fidelity, but also serves to repair DNA lesions arising as a result of exposure to mutagens. Polδ has been shown to be important for multiple forms of DNA repair, including nucleotide excision repair, double strand break repair, base excision repair, and mismatch repair. A growing number of studies in the past decade have linked germline and sporadic mutations in POLD1 and the other subunits of Polδ with human pathologies. Mutations in Polδ in mice and humans lead to genomic instability, mutator phenotype and tumorigenesis. The advent of genome sequencing techniques has identified damaging mutations in the proofreading domain of POLD1 as the underlying cause of some inherited cancers, and suggested that mutations in POLD1 may influence therapeutic management. In addition, mutations in POLD1 have been identified in the developmental disorders of mandibular hypoplasia, deafness, progeroid features and lipodystrophy and atypical Werner syndrome, while changes in expression or activity of POLD1 have been linked to senescence and aging. Intriguingly, some recent evidence suggests POLD1 function may also be altered in diabetes. We provide an overview of critical Polδ activities in the context of these pathologic conditions.",,"['Nicolas, Emmanuelle', 'Golemis, Erica A.', 'Arora, Sanjeevani']",,,,
,PMC,Towards RNA Nanoparticle Vaccines: Synergizing RNA and Inorganic Nanoparticles to Achieve Immuno-potentiation,http://dx.doi.org/10.1002/wnan.1415,PMC5443121,,,"Traditionally, vaccines have been composed of live attenuated or killed micro-organisms. Alternatively, individual protein subunits or other molecular components of the micro-organism can serve as the antigen and trigger an antibody response by the immune system. The immune system is a coordinated molecular and cellular response that works in concert to check the spread of infection. In the past decade, there has been much progress on DNA vaccines. DNA vaccination includes using the coding segments of a viral or bacterial genome to generate an immune response. However, the potential advantage of combining an RNA molecule with inorganic nanoparticle delivery should be considered, with the goal to achieve immuno-synergy between the two and to overcome some of the current limitations of DNA vaccines and traditional vaccines.",,"['DeLong, Robert K.', 'Curtis, Chandler B.']",,,,
,PMC,The Effects of Live Attenuated Influenza Vaccine on Nasopharyngeal Bacteria in Healthy 2 to 4 Year Olds. A Randomized Controlled Trial,http://dx.doi.org/10.1164/rccm.201510-2000OC,PMC4910891,,,"Rationale: Viral infections of the upper respiratory tract may influence the commensal nasopharyngeal bacteria. Changes in the bacterial niche could affect transmission dynamics. Attenuated vaccine viruses can be used to investigate this empirically in humans. Objectives: To study the effects of mild viral upper respiratory infections on nasopharyngeal bacterial colonization using live attenuated influenza vaccine (LAIV) as a surrogate. Methods: We used trivalent LAIV to evaluate the effects of viral infection on bacterial carriage and density of Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, and Staphylococcus aureus. A total of 151 healthy children were randomized 1:1 to receive the vaccine starting either at recruitment (n = 74) or 28 days later (n = 77) in a stepped wedge fashion, allowing comparisons between recipients and nonrecipients as well as whole-group comparisons pre- and postvaccination. Bacterial carriage and density were determined using quantitative polymerase chain reaction assays. Measurements and Main Results: A total of 151 children were recruited, 77 in the LAIV group and 74 in the control group. LAIV recipients (n = 63 analyzed) showed an apparent transient increase in H. influenzae carriage but no further significant differences in carriage prevalence of the four bacterial species compared with controls (n = 72 analyzed). S. pneumoniae density was substantially higher in vaccine recipients (16,687 vs. 1935 gene copies per milliliter) 28 days after the first dose (P < 0.001). Whole-group multivariable analysis (prevaccine, after one dose, and after two doses) also showed increases in density of other species and H. influenzae carriage prevalence. Conclusions: In the absence of any safety signals despite widespread use of the vaccine, these findings suggest that bacterial density, and thus transmission rates among children and to people in other age groups, may rise following attenuated influenza infections without associated clinical disease. LAIV could therefore be used as an experimental tool to elucidate the dynamics of transmission of nasopharyngeal bacteria.",,"['Thors, Valtyr', 'Christensen, Hannah', 'Morales-Aza, Begonia', 'Vipond, Ian', 'Muir, Peter', 'Finn, Adam']",,,,
,PMC,Gene Expression and Antiviral Activity of Interleukin-35 in Response to Influenza A Virus Infection,http://dx.doi.org/10.1074/jbc.M115.693101,PMC4974397,,,"Interleukin-35 (IL-35) is a newly described member of the IL-12 family. It has been reported to inhibit inflammation and autoimmune inflammatory disease and can increase apoptotic sensitivity. Little is known about the role of IL-35 during viral infection. Herein, high levels of IL-35 were found in peripheral blood mononuclear cells and throat swabs from patients with seasonal influenza A virus (IAV) relative to healthy individuals. IAV infection of human lung epithelial and primary cells increased levels of IL-35 mRNA and protein. Further studies demonstrated that IAV-induced IL-35 transcription is regulated by NF-κB. IL-35 expression was significantly suppressed by selective inhibitors of cyclooxygenase-2 (COX-2) and inducible nitric-oxide synthase, indicating their involvement in IL-35 expression. Interestingly, IL-35 production may have suppressed IAV RNA replication and viral protein synthesis via induction of type I and III interferons (IFN), leading to activation of downstream IFN effectors, including double-stranded RNA-dependent protein kinase, 2′,5′-oligoadenylate synthetase, and myxovirus resistance protein. IL-35 exhibited extensive antiviral activity against the hepatitis B virus, enterovirus 71, and vesicular stomatitis virus. Our results demonstrate that IL-35 is a novel IAV-inducible cytokine, and its production elicits antiviral activity.",,"['Wang, Li', 'Zhu, Shengli', 'Xu, Gang', 'Feng, Jian', 'Han, Tao', 'Zhao, Fanpeng', 'She, Ying-Long', 'Liu, Shi', 'Ye, Linbai', 'Zhu, Ying']",,,,
,PMC,Salt Effects on the Thermodynamics of a Frameshifting RNA Pseudoknot under Tension,http://dx.doi.org/10.1016/j.jmb.2016.06.002,PMC5590673,,,"Because of the potential link between −1 programmed ribosomal frameshifting and response of a pseudoknot (PK) RNA to force, a number of single-molecule pulling experiments have been performed on PKs to decipher the mechanism of programmed ribosomal frameshifting. Motivated in part by these experiments, we performed simulations using a coarse-grained model of RNA to describe the response of a PK over a range of mechanical forces (fs) and monovalent salt concentrations (Cs). The coarse-grained simulations quantitatively reproduce the multistep thermal melting observed in experiments, thus validating our model. The free energy changes obtained in simulations are in excellent agreement with experiments. By varying f and C, we calculated the phase diagram that shows a sequence of structural transitions, populating distinct intermediate states. As f and C are changed, the stem–loop tertiary interactions rupture first, followed by unfolding of the 3′-end hairpin (I⇌F). Finally, the 5′-end hairpin unravels, producing an extended state (E⇌I). A theoretical analysis of the phase boundaries shows that the critical force for rupture scales as (logC(m))(α) with α=1 (0.5) for E⇌I (I⇌F) transition. This relation is used to obtain the preferential ion–RNA interaction coefficient, which can be quantitatively measured in single-molecule experiments, as done previously for DNA hairpins. A by-product of our work is the suggestion that the frameshift efficiency is likely determined by the stability of the 5′-end hairpin that the ribosome first encounters during translation.",,"['Hori, Naoto', 'Denesyuk, Natalia A.', 'Thirumalai, D.']",,,,
,PMC,Decoding protein networks during virus entry by quantitative proteomics,http://dx.doi.org/10.1016/j.virusres.2015.09.006,PMC4914609,26365680,CC BY-NC-ND,"Virus entry into host cells relies on interactions between viral and host structures including lipids, carbohydrates and proteins. Particularly, protein–protein interactions between viral surface proteins and host proteins as well as secondary host protein–protein interactions play a pivotal role in coordinating virus binding and uptake. These interactions are dynamic and frequently involve multiprotein complexes. In the past decade mass spectrometry based proteomics methods have reached sensitivities and high throughput compatibilities of genomics methods and now allow the reliable quantitation of proteins in complex samples from limited material. As proteomics provides essential information on the biologically active entity namely the protein, including its posttranslational modifications and its interactions with other proteins, it is an indispensable method in the virologist's toolbox. Here we review protein interactions during virus entry and compare classical biochemical methods to study entry with novel technically advanced quantitative proteomics techniques. We highlight the value of quantitative proteomics in mapping functional virus entry networks, discuss the benefits and limitations and illustrate how the methodology will help resolve unsettled questions in virus entry research in the future.",2016 Jun 15,"['Gerold, Gisa', 'Bruening, Janina', 'Pietschmann, Thomas']",Virus Res,,,
,PMC,Epidemiology of a Novel Recombinant Middle East Respiratory Syndrome Coronavirus in Humans in Saudi Arabia,http://dx.doi.org/10.1093/infdis/jiw236,PMC5712457,,,"BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans. Fundamental questions about circulating viruses and transmission routes remain. METHODS: We assessed routinely collected epidemiologic data for MERS-CoV cases reported in Saudi Arabia during 1 January– 30 June 2015 and conducted a more detailed investigation of cases reported during February 2015. Available respiratory specimens were obtained for sequencing. RESULTS: During the study period, 216 MERS-CoV cases were reported. Full genome (n = 17) or spike gene sequences (n = 82) were obtained from 99 individuals. Most sequences (72 of 99 [73%]) formed a discrete, novel recombinant subclade (NRC-2015), which was detected in 6 regions and became predominant by June 2015. No clinical differences were noted between clades. Among 87 cases reported during February 2015, 13 had no recognized risks for secondary acquisition; 12 of these 13 also denied camel contact. Most viruses (8 of 9) from these 13 individuals belonged to NRC-2015. DISCUSSIONS: Our findings document the spread and eventual predominance of NRC-2015 in humans in Saudi Arabia during the first half of 2015. Our identification of cases without recognized risk factors but with similar virus sequences indicates the need for better understanding of risk factors for MERS-CoV transmission.",,"['Assiri, Abdullah M.', 'Midgley, Claire M.', 'Abedi, Glen R.', 'Saeed, Abdulaziz Bin', 'Almasri, Malak M.', 'Lu, Xiaoyan', 'Al-Abdely, Hail M.', 'Abdalla, Osman', 'Mohammed, Mutaz', 'Algarni, Homoud S.', 'Alhakeem, Raafat F.', 'Sakthivel, Senthilkumar K.', 'Nooh, Randa', 'Alshayab, Zainab', 'Alessa, Mohammad', 'Srinivasamoorthy, Ganesh', 'AlQahtani, Saeed Yahya', 'Kheyami, Ali', 'HajOmar, Waleed Husein', 'Banaser, Talib M.', 'Esmaeel, Ahmad', 'Hall, Aron J.', 'Curns, Aaron T.', 'Tamin, Azaibi', 'Alsharef, Ali Abraheem', 'Erdman, Dean', 'Watson, John T.', 'Gerber, Susan I.']",,,,
,PMC,Molecular analysis of Idiopathic Subglottic Stenosis for Mycobacterium species: A North American Airway Collaborative (NoAAC) TS-04 study,http://dx.doi.org/10.1002/lary.26097,PMC5156582,,,"RATIONALE: Idiopathic subglottic stenosis (iSGS) is an unexplained obstruction involving the lower laryngeal and upper tracheal airway. Persistent mucosal inflammation is a hallmark of the disease. Epithelial microbiota dysbiosis is found in other chronic inflammatory mucosal diseases; however, the relationship between tracheal microbiota composition and iSGS is unknown. OBJECTIVES: Given the critical role for host defense at mucosal barriers, we analyzed tissue specimens from iSGS patients for the presence of microbial pathogens. METHODS: Utilizing 20 human iSGS, 20 intubation-related tracheal stenosis (iLTS) and 10 healthy control specimens we applied molecular, immunohistochemical, electron microscopic, immunologic and Sanger™ sequencing techniques. MAIN RESULTS: With unbiased culture-independent nucleic acid, protein, and immunologic approaches, we demonstrate that Mycobacterium species are uniquely associated with iSGS. Phylogenetic analysis of the mycobacterial virulence factor rpoB suggests that rather than Mycobacterium Tuberculosis (Mtb), a variant member of the Mycobacterium Tuberculosis Complex (MtbC), or a closely related novel mycobacterium is present in iSGS specimens. CONCLUSIONS: These studies identify a novel pathogenic role for established large airway bacteria, and provide new targets for future therapeutic intervention. LEVEL OF EVIDENCE: NA.",,"['Gelbard, Alexander', 'Katsantonis, Nicolas-George', 'Mizuta, Masanobu', 'Newcomb, Dawn', 'Rotsinger, Joseph', 'Rousseau, Bernard', 'Daniero, James J.', 'Edell, Eric S.', 'Ekbom, Dale C.', 'Kasperbauer, Jan L.', 'Hillel, Alexander T.', 'Yang, Liying', 'Garrett, C. Gaelyn', 'Netterville, James L.', 'Wootten, Christopher T.', 'Francis, David O.', 'Stratton, Charles', 'Jenkins, Kevin', 'McGregor, Tracy L.', 'Gaddy, Jennifer A.', 'Blackwell, Timothy S.', 'Drake, Wonder P.']",,,,
,PMC,Global patterns of zoonotic disease in mammals,http://dx.doi.org/10.1016/j.pt.2016.04.007,PMC4921293,,,"As the frequency and prevalence of zoonotic diseases increase worldwide, investigating how mammal host distributions determine patterns of human disease and predicting which regions are at greatest risk for future zoonotic disease emergence are two goals which both require better understanding the current distributions of zoonotic hosts and pathogens. Here we review the existing data about mammalian host species, comparing and contrasting these patterns against global maps of zoonotic hosts from all 27 orders of terrestrial mammals. We discuss the zoonotic potential of host species from the top six most species-rich mammal groups, and review the literature to identify analytical and conceptual gaps that must be addressed to improve our ability to generate testable predictions about zoonotic diseases originating from wild mammals.",,"['Han, Barbara A.', 'Kramer, Andrew M.', 'Drake, John M.']",,,,
,PMC,Autocrine Complement Inhibits IL10-Dependent T-Cell Mediated Antitumor Immunity to Promote Tumor Progression,http://dx.doi.org/10.1158/2159-8290.CD-15-1412,PMC5010476,,,"In contrast to its inhibitory effects on many cells, IL-10 activates CD8(+) tumor infiltrating lymphocytes (TILs) and enhances their antitumor activity. However, CD8(+) TILs do not routinely express IL-10 as autocrine complement C3 inhibits IL-10 production through complement receptors C3aR and C5aR. CD8(+) TILs from C3-deficient mice, however, express IL-10 and exhibit enhanced effector function. C3-deficient mice are resistant to tumor development in a T cell- and IL-10-dependent manner; human TILs expanded with IL-2 plus IL-10 increase the killing of primary tumors in vitro compared to IL-2 treated TILs. Complement-mediated inhibition of antitumor immunity is independent of the PD-1/PD-L1 immune checkpoint pathway. Our findings suggest that complement receptors C3aR and C5aR expressed on CD8(+) TILs represent a novel class of immune checkpoints that could be targeted for tumor immunotherapy. Moreover, incorporation of IL-10 in the expansion of TILs and in gene-engineered T cells for adoptive cell therapy enhances their antitumor efficacy.",,"['Wang, Yu', 'Sun, Sheng-Nan', 'Liu, Qing', 'Yu, Yang-Yang', 'Guo, Jian', 'Wang, Kun', 'Xing, Bao-Cai', 'Zheng, Qing-Feng', 'Campa, Michael J.', 'Patz, Edward F.', 'Li, Shi-You', 'He, You-Wen']",,,,
,PMC,Cordycepin induces apoptosis in human liver cancer HepG2 cells through extrinsic and intrinsic signaling pathways,http://dx.doi.org/10.3892/ol.2016.4706,PMC4950226,,,"Cordycepin, also termed 3′-deoxyadenosine, is a nucleoside analogue from Cordyceps sinensis and has been reported to demonstrate numerous biological and pharmacological properties. Our previous study illustrated that the anti-tumor effect of cordycepin may be associated with apoptosis. In the present study, the apoptotic effect of cordycepin on HepG2 cells was investigated using 4′,6-diamidino-2-phenylindole, tetraethylbenzimidazolylcarbocyanine iodide and propidium iodide staining analysis and flow cytometry. The results showed that cordycepin exhibited the ability to inhibit HepG2 cells in a time- and dose-dependent manner when cells produced typical apoptotic morphological changes, including chromatin condensation, the accumulation of sub-G1 cells and change mitochondrial permeability. A potential mechanism for cordycepin-induced apoptosis of human liver cancer HepG2 cells may occur through the extrinsic signaling pathway mediated by the transmembrane Fas-associated with death domain protein. Apoptosis was also associated with Bcl-2 family protein regulation, leading to altered mitochondrial membrane permeability and resulting in the release of cytochrome c into the cytosol. The activation of the caspase cascade is responsible for the execution of apoptosis. In conclusion, cordycepin-induced apoptosis in HepG2 cells involved the extrinsic and intrinsic signaling pathway and was primarily regulated by the Bcl-2 family proteins.",,"['Shao, Le-Wen', 'Huang, Li-Hua', 'Yan, Sheng', 'Jin, Jian-Di', 'Ren, Shao-Yan']",,,,
,PMC,Role for phospholipid acyl chains and cholesterol in pulmonary infections and inflammation,http://dx.doi.org/10.1189/jlb.4VMR0316-103R,PMC5069085,,,"Bacterial and viral respiratory tract infections result in millions of deaths worldwide and are currently the leading cause of death from infection. Acute inflammation is an essential element of host defense against infection, but can be damaging to the host when left unchecked. Effective host defense requires multiple lipid mediators, which collectively have proinflammatory and/or proresolving effects on the lung. During pulmonary infections, phospholipid acyl chains and cholesterol can be chemically and enzymatically oxidized, as well as truncated and modified, producing complex mixtures of bioactive lipids. We review recent evidence that phospholipids and cholesterol and their derivatives regulate pulmonary innate and adaptive immunity during infection. We first highlight data that oxidized phospholipids generated in the lung during infection stimulate pattern recognition receptors, such as TLRs and scavenger receptors, thereby amplifying the pulmonary inflammatory response. Next, we discuss evidence that oxidation of endogenous pools of cholesterol during pulmonary infections produces oxysterols that also modify the function of both innate and adaptive immune cells. Last, we conclude with data that n-3 polyunsaturated fatty acids, both in the form of phospholipid acyl chains and through enzymatic processing into endogenous proresolving lipid mediators, aid in the resolution of lung inflammation through distinct mechanisms. Unraveling the complex mechanisms of induction and function of distinct classes of bioactive lipids, both native and modified, may hold promise for developing new therapeutic strategies for improving pulmonary outcomes in response to infection.",,"['Shaikh, Saame Raza', 'Fessler, Michael B.', 'Gowdy, Kymberly M.']",,,,
,PMC,The Herpes Simplex Virus Virion Host Shutoff Protein Enhances Translation of Viral True Late mRNAs Independently of Suppressing Protein Kinase R and Stress Granule Formation,http://dx.doi.org/10.1128/JVI.03180-15,PMC4907241,,,"The herpes simplex virus (HSV) virion host shutoff (vhs) RNase destabilizes cellular and viral mRNAs, suppresses host protein synthesis, dampens antiviral responses, and stimulates translation of viral mRNAs. vhs mutants display a host range phenotype: translation of viral true late mRNAs is severely impaired and stress granules accumulate in HeLa cells, while translation proceeds normally in Vero cells. We found that vhs-deficient virus activates the double-stranded RNA-activated protein kinase R (PKR) much more strongly than the wild-type virus does in HeLa cells, while PKR is not activated in Vero cells, raising the possibility that PKR might play roles in stress granule induction and/or inhibiting translation in restrictive cells. We tested this possibility by evaluating the effects of inactivating PKR. Eliminating PKR in HeLa cells abolished stress granule formation but had only minor effects on viral true late protein levels. These results document an essential role for PKR in stress granule formation by a nuclear DNA virus, indicate that induction of stress granules is the consequence rather than the cause of the translational defect, and are consistent with our previous suggestion that vhs promotes translation of viral true late mRNAs by preventing mRNA overload rather than by suppressing eIF2α phosphorylation. IMPORTANCE The herpes simplex virus vhs RNase plays multiple roles during infection, including suppressing PKR activation, inhibiting the formation of stress granules, and promoting translation of viral late mRNAs. A key question is the extent to which these activities are mechanistically connected. Our results demonstrate that PKR is essential for stress granule formation in the absence of vhs, but at best, it plays a secondary role in suppressing translation of viral mRNAs. Thus, the ability of vhs to promote translation of viral mRNAs can be largely uncoupled from PKR suppression, demonstrating that this viral RNase modulates at least two distinct aspects of RNA metabolism.",,"['Dauber, Bianca', 'Poon, David', 'dos Santos, Theodore', 'Duguay, Brett A.', 'Mehta, Ninad', 'Saffran, Holly A.', 'Smiley, James R.']",,,,
,PMC,Characterization of Epitope-Specific Anti-Respiratory Syncytial Virus (Anti-RSV) Antibody Responses after Natural Infection and after Vaccination with Formalin-Inactivated RSV,http://dx.doi.org/10.1128/JVI.00235-16,PMC4907225,,,"Antibodies against the fusion (F) protein of respiratory syncytial virus (RSV) play an important role in the protective immune response to this important respiratory virus. Little is known, however, about antibody levels against multiple F-specific epitopes induced by infection or after vaccination against RSV, while this is important to guide the evaluation of (novel) vaccines. In this study, we analyzed antibody levels against RSV proteins and F-specific epitopes in human sera and in sera of vaccinated and experimentally infected cotton rats and the correlation thereof with virus neutralization. Analysis of human sera revealed substantial diversity in antibody levels against F-, G (attachment)-, and F-specific epitopes between individuals. The highest correlation with virus neutralization was observed for antibodies recognizing prefusion-specific antigenic site Ø. Nevertheless, our results indicate that high levels of antibodies targeting other parts of the F protein can also mediate a potent antiviral antibody response. In agreement, sera of experimentally infected cotton rats contained high neutralizing activity despite lacking antigenic site Ø-specific antibodies. Strikingly, vaccination with formalin-inactivated RSV (FI-RSV) exclusively resulted in the induction of poorly neutralizing antibodies against postfusion-specific antigenic site I, although antigenic sites I, II, and IV were efficiently displayed in FI-RSV. The apparent immunodominance of antigenic site I in FI-RSV likely explains the low levels of neutralizing antibodies upon vaccination and challenge and may play a role in the vaccination-induced enhancement of disease observed with such preparations. IMPORTANCE RSV is an importance cause of hospitalization of infants. The development of a vaccine against RSV has been hampered by the disastrous results obtained with FI-RSV vaccine preparations in the 1960s that resulted in vaccination-induced enhancement of disease. To get a better understanding of the antibody repertoire induced after infection or after vaccination against RSV, we investigated antibody levels against fusion (F) protein, attachment (G) protein, and F-specific epitopes in human and animal sera. The results indicate the importance of prefusion-specific antigenic site Ø antibodies as well as of antibodies targeting other epitopes in virus neutralization. However, vaccination of cotton rats with FI-RSV specifically resulted in the induction of weakly neutralizing, antigenic site I-specific antibodies, which may play a role in the enhancement of disease observed after vaccination with such preparations.",,"['Widjaja, Ivy', 'Wicht, Oliver', 'Luytjes, Willem', 'Leenhouts, Kees', 'Rottier, Peter J. M.', 'van Kuppeveld, Frank J. M.', 'Haijema, Bert Jan', 'de Haan, Cornelis A. M.']",,,,
,PMC,Neutrophils and viral-induced neurologic disease,http://dx.doi.org/10.1016/j.clim.2016.05.009,PMC5145788,,,"Infection of the central nervous system (CNS) by neurotropic viruses represents an increasing worldwide problem in terms of morbidity and mortality for people of all ages. Although unique structural features of the blood-brain-barrier (BBB) provide a physical and physiological barrier, a number of neurotropic viruses are able to enter the CNS resulting in a variety of pathological outcomes. Nonetheless, antigen-specific lymphocytes are ultimately able to accumulate within the CNS and contribute to defense by reducing or eliminating the invading viral pathogen. Alternatively, infiltration of activated cells of the immune system may be detrimental, as these cells can contribute to neuropathology that may result in long-term cellular damage or death. More recently, myeloid cells e.g. neutrophils have been implicated in contributing to both host defense and disease in response to viral infection of the CNS. This review highlights recent studies using coronavirus-induced neurologic disease as a model to determine how neutrophils affect effective control of viral replication as well as demyelination.",,"['Grist, Jonathan J.', 'Marro, Brett', 'Lane, Thomas E.']",,,,
,PMC,Approved Antiviral Drugs over the Past 50 Years,http://dx.doi.org/10.1128/CMR.00102-15,PMC4978613,,,"Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2′-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2′-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox). Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide.",,"['De Clercq, Erik', 'Li, Guangdi']",,,,
,PMC,Innate Immune Evasion Strategies of DNA and RNA viruses,http://dx.doi.org/10.1016/j.mib.2016.05.015,PMC4983539,,,"Upon infection, both DNA and RNA viruses can be sensed by pattern recognition receptors (PRRs) in the cytoplasm or the nucleus to activate antiviral innate immunity. Sensing of viral products leads to the activation of a signaling cascade that ultimately results in transcriptional activation of Type I and III interferons, as well as other antiviral genes that mediate viral clearance and inhibit viral spread. Therefore, in order for viruses to replicate and spread efficiently, they must inhibit the host signaling pathways that induce the innate antiviral immune response. In this review, we will highlight recent advances the understanding of the mechanisms by which viruses evade PRR detection, intermediate signaling molecule activation, transcription factor activation, and the actions of antiviral proteins.",,"['Beachboard, Dia C.', 'Horner, Stacy M.']",,,,
,PMC,Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus,http://dx.doi.org/10.1080/21645515.2016.1177688,PMC5027702,,,"To determine if a hypersensitive-type lung pathology might occur when mice were given an inactivated MERS-CoV vaccine and challenged with infectious virus as was seen with SARS-CoV vaccines, we prepared and vaccinated mice with an inactivated MERS-CoV vaccine. Neutralizing antibody was induced by vaccine with and without adjuvant and lung virus was reduced in vaccinated mice after challenge. Lung mononuclear infiltrates occurred in all groups after virus challenge but with increased infiltrates that contained eosinophils and increases in the eosinophil promoting IL-5 and IL-13 cytokines only in the vaccine groups. Inactivated MERS-CoV vaccine appears to carry a hypersensitive-type lung pathology risk from MERS-CoV infection that is similar to that found with inactivated SARS-CoV vaccines from SARS-CoV infection.",,"['Agrawal, Anurodh Shankar', 'Tao, Xinrong', 'Algaissi, Abdullah', 'Garron, Tania', 'Narayanan, Krishna', 'Peng, Bi-Hung', 'Couch, Robert B.', 'Tseng, Chien-Te K.']",,,,
,PMC,Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses,http://dx.doi.org/10.1016/j.immuni.2016.05.006,PMC4917442,,,"Two zoonotic coronaviruses (CoV), SARS-CoV and MERS-CoV have crossed species to cause severe human respiratory disease. Here, we showed that induction of airway memory CD4(+) T cells specific for a conserved epitope shared by SARS-CoV and MERS-CoV is a potential strategy for developing pan-coronavirus vaccines. Airway memory CD4(+) T cells differed phenotypically and functionally from lung-derived cells and were crucial for protection against both CoVs in mice. Protection was interferon-γ-dependent and required early induction of robust innate and virus-specific CD8(+) T cell responses. The conserved epitope was also recognized in SARS-CoV and MERS-CoV-infected human leukocyte antigen DR2 and DR3 transgenic mice, indicating potential relevance in human populations. Additionally, this epitope was cross-protective between human and bat CoVs, the progenitors for many human CoVs. Vaccine strategies that induce airway memory CD4(+) T cells targeting conserved epitopes may have broad applicability in the context of new CoV and other respiratory virus outbreaks.",,"['Zhao, Jincun', 'Zhao, Jingxian', 'Mangalam, Ashutosh K.', 'Channappanavar, Rudragouda', 'Fett, Craig', 'Meyerholz, David K.', 'Agnihothram, Sudhakar', 'Baric, Ralph S.', 'David, Chella S.', 'Perlman, Stanley']",,,,
,PMC,Platelet-derived growth factor-α receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer,http://dx.doi.org/10.1038/nmicrobiol.2016.82,PMC4918640,,,"Human cytomegalovirus (HCMV) encodes at least 25 membrane glycoproteins that are found in the viral envelope(1). While gB represents the fusion protein, two glycoprotein complexes control the tropism of the virus: the gHgLgO trimer is involved in the infection of fibroblasts, while the gHgLpUL128L pentamer is required for infection of endothelial, epithelial and myeloid cells(2–5). Two reports suggested that gB binds to ErbB1 and PDGFRα(6,7), however these results do not explain the tropism of the virus and were recently challenged(8,9). Here we provide a 19Å reconstruction for the gHgLgO trimer and show that it binds with high affinity through the gO subunit to PDGFRα, which is expressed on fibroblasts but not on epithelial cells. We also provide evidences that the trimer is essential for viral entry in all cell types. Furthermore, we identified the pentamer as a trigger for the ErbB pathway, which is essential for infection of epithelial cells. These findings help explain the broad tropism of HCMV and indicate that PDGFRα and the viral gO subunit could be targeted by novel anti-viral therapies.",,"['Kabanova, Anna', 'Marcandalli, Jessica', 'Zhou, Tongqing', 'Bianchi, Siro', 'Baxa, Ulrich', 'Tsybovsky, Yaroslav', 'Lilleri, Daniele', 'Silacci-Fregni, Chiara', 'Foglierini, Mathilde', 'Fernandez-Rodriguez, Blanca Maria', 'Druz, Aliaksandr', 'Zhang, Baoshan', 'Geiger, Roger', 'Pagani, Massimiliano', 'Sallusto, Federica', 'Kwong, Peter D.', 'Corti, Davide', 'Lanzavecchia, Antonio', 'Perez, Laurent']",,,,
,PMC,Opportunistic intruders: how viruses orchestrate ER functions to infect cells,http://dx.doi.org/10.1038/nrmicro.2016.60,PMC5272919,,,"Viruses subvert the functions of their host cells to replicate and form new viral progeny. The endoplasmic reticulum (ER) has been identified as a central organelle that governs the intracellular interplay between viruses and hosts. In this Review, we analyse how viruses from vastly different families converge on this unique intracellular organelle during infection, co-opting some of the endogenous functions of the ER to promote distinct steps of the viral life cycle from entry and replication to assembly and egress. The ER can act as the common denominator during infection for diverse virus families, thereby providing a shared principle that underlies the apparent complexity of relationships between viruses and host cells. As a plethora of information illuminating the molecular and cellular basis of virus–ER interactions has become available, these insights may lead to the development of crucial therapeutic agents.",,"['Ravindran, Madhu Sudhan', 'Bagchi, Parikshit', 'Cunningham, Corey Nathaniel', 'Tsai, Billy']",,,,
,PMC,How I treat respiratory viral infections in the setting of intensive chemotherapy or hematopoietic cell transplantation,http://dx.doi.org/10.1182/blood-2016-01-634873,PMC4891952,,,"The widespread use of multiplex molecular diagnostics has led to a significant increase in the detection of respiratory viruses in patients undergoing cytotoxic chemotherapy and hematopoietic cell transplantation (HCT). Respiratory viruses initially infect the upper respiratory tract and then progress to lower respiratory tract disease in a subset of patients. Lower respiratory tract disease can manifest itself as airflow obstruction or viral pneumonia, which can be fatal. Infection in HCT candidates may require delay of transplantation. The risk of progression differs between viruses and immunosuppressive regimens. Risk factors for progression and severity scores have been described, which may allow targeting treatment to high-risk patients. Ribavirin is the only antiviral treatment option for noninfluenza respiratory viruses; however, high-quality data demonstrating its efficacy and relative advantages of the aerosolized versus oral form are lacking. There are significant unmet needs, including data defining the virologic characteristics and clinical significance of human rhinoviruses, human coronaviruses, human metapneumovirus, and human bocavirus, as well as the need for new treatment and preventative options.",,"['Waghmare, Alpana', 'Englund, Janet A.', 'Boeckh, Michael']",,,,
,PMC,Rhinovirus species and clinical characteristics in the first wheezing episode in children,http://dx.doi.org/10.1002/jmv.24587,PMC5140033,,,"The clinical data on the first wheezing episodes induced by different rhinovirus (RV) species are still limited. We aimed to investigate the prevalence of RV genotypes, sensitization status and clinical characteristics of patients having a respiratory infection caused by either different RV species or other respiratory viruses. The study enrolled 111 patients (aged 3–23 months, 79% hospitalized, 76% with RV infection) with the first wheezing episode. RV-specific sequences were identified by partial sequencing of VP4/VP2 and 5′ non-coding regions with 80% success rate. The investigated clinical and laboratory variables included atopic characteristics and illness severity, parental atopic illnesses, and parental smoking. Of the study children, 56% percent had ≥1 atopic characteristic (atopy, eczema and/or blood eosinophil count ≥0.4×10(9)/L) and 23% were sensitised to allergens. RV-C was detected in 58% of RV positive samples, followed by RV-A (20%) and RV-B (1.2%). Children with RV-A and RV-C induced wheezing were older (p = 0.014) and had more atopic characteristics (p = 0.001) than those with non-RV. RV-A and RV-C illnesses had shorter duration of preadmission symptoms and required more bronchodilator use at the ward than non-RV illnesses (both p < 0.05, respectively) RV-C is the most common cause of severe early wheezing. Atopic and illness severity features are associated with children having RV-A or RV-C induced first wheezing episode rather than with children having a non-RV induced wheezing.",,"['Turunen, Riitta', 'Jartti, Tuomas', 'Bochkov, Yury', 'Gern, James', 'Vuorinen, Tytti']",,,,
,PMC,PLA Micro- and Nano-Particles,http://dx.doi.org/10.1016/j.addr.2016.05.020,PMC5133193,,,"Poly(D,L-lactic acid) (PLA) has been widely used for various biomedical applications for its biodegradable, biocompatible, and nontoxic properties. Various methods, such as emulsion, salting out, and precipitation, have been used to make better PLA micro and nano-particle formulations. They are widely used as controlled drug delivery systems of therapeutic molecules, including proteins, genes, vaccines, and anti-cancer drugs. Even though PLA-based particles have challenges to overcome, such as low drug loading capacity, low encapsulation efficiency, and terminal sterilization, continuous innovations in particulate formulations will lead to development of clinically useful formulations.",,"['Lee, Byung Kook', 'Yun, Yeonhee', 'Park, Kinam']",,,,
,PMC,Global Health Education in Pulmonary and Critical Care Medicine Fellowships,http://dx.doi.org/10.1513/AnnalsATS.201601-028PS,PMC5018927,,,"A growing number of pulmonary and critical care medicine fellowship programs in the United States offer global health training opportunities. Formal, integrated global health programs within pulmonary and critical care fellowships are relatively new but are built on principles and ideals of global health that focus on the mutually beneficial exchange of knowledge and social justice. Although core competencies consistent with these overarching themes in global health education have not been formalized for pulmonary and critical care trainees, relevant competency areas include clinical knowledge, international research training, cultural competency, and clinical and research capacity building. Existing global health education in U.S. pulmonary and critical care medicine training programs can generally be classified as one of three different models: integrated global health tracks, global health electives, and additional research years. Successful global health education programs foster partnerships and collaborations with international sites that emphasize bidirectional exchange. This bidirectional exchange includes ongoing, equitable commitments to mutual opportunities for training and professional development, including a focus on the particular knowledge and skill sets critical for addressing the unique priorities of individual countries. However, barriers related to the availability of mentorship, funding, and dedicated time exist to expanding global health education in pulmonary and critical care medicine. The implementation of global health training within pulmonary and critical care medicine programs requires continued optimization, but this training is essential to prepare the next generation of physicians to address the global aspects of respiratory disease and critical illness.",,"['Siddharthan, Trishul', 'North, Crystal M.', 'Attia, Engi F.', 'Christiani, David C.', 'Checkley, William', 'West, T. Eoin']",,,,
,PMC,Wanted: better public health training for family physicians,,PMC4907550,,,,,"['B-Lajoie, Marie-Renée', 'Chartier, Lucas']",,,,
,PMC,Persistence of clinical signs associated with rotavirus following an outbreak of porcine epidemic diarrhea (PED) on a farrow-to-grow swine operation in southwestern Ontario,,PMC4866665,,,"Clinical signs attributed to porcine epidemic diarrhea (PED) persisted for several months in a southwestern Ontario farm following an outbreak of PED. Extensive testing revealed rotavirus infection and absence of PED in nursing and nursery pigs, highlighting the importance of repeated diagnostic testing following a disease outbreak.",,"['Tenbergen, Ryan', 'O’Sullivan, Terri', 'Poljak, Zvonimir', 'DeLay, Josepha', 'Charbonneau, George']",,,,
,PMC,The Evolving Spectrum of Ciliopathies and Respiratory Disease,http://dx.doi.org/10.1097/MOP.0000000000000358,PMC4904788,,,"PURPOSE OF REVIEW: Research on the biology of cilia, complex hair-like cellular organelles, has greatly informed our understanding of its crucial role in respiratory health and the pathogenesis of Primary Ciliary Dyskinesia (PCD), including the genetics behind this condition. This review will summarize the current state of the art in the field highlighting its clinical implications. RECENT FINDINGS: The genetics of PCD have exploded over the past few years as knowledge acquired from model systems has permitted the identification of genes that are key components of the ciliary apparatus and its function. In addition clinical criteria and diagnostic tools have emerged that are permitting more clear identification of affected individuals. SUMMARY: The rate of progress in the field continues to accelerate through international collaborative efforts and standardization of methods. Although the genetics behind PCD are complex given the large number of genes associated with disease as well as the large number of possible mutations even at the individual gene level, this knowledge is rapidly translating in improved diagnostics and hopefully in the near future in the identification of potential therapeutics.",,"Milla, Carlos E.",,,,
,PMC,Real-time estimation of the hospitalization fatality risk of influenza A(H1N1)pdm09 in Hong Kong,http://dx.doi.org/10.1017/S0950268815003179,PMC5528870,,,"During the early stage of an epidemic, timely and reliable estimation of the severity are important for predicting the impact that the influenza viruses will have in the population. We obtained age-specific deaths and hospitalizations among patients with laboratory-confirmed H1N1pdm09 infections from June 2009 through December 2009 in Hong Kong. We retrospectively obtained the real-time estimates of the hospitalization fatality risk, using crude estimation or allowing for right-censoring for final status in some patients. Models accounting for right-censoring performed better than models without adjustments. The risk of deaths among hospitalized patients with confirmed H1N1pdm09 increased with age. Reliable estimates of the HFR could be obtained before the peak of the first wave of H1N1pdm09 in young and middle-aged adults but after the peak in the elderly. In the next influenza pandemic, timely estimation of the hospitalization fatality risk will contribute to risk assessment and disease control.",,"['Wong, Jessica Y.', 'Wu, Peng', 'Lau, Eric H. Y.', 'Tsang, Tim K.', 'Fang, Vicky J.', 'Ho, Lai-Ming', 'Cowling, Benjamin J.']",,,,
,PMC,Glycosaminoglycans and infection,,PMC4975577,,,"Glycosaminoglycans (GAGs) are complex linear polysaccharides expressed in intracellular compartments, at the cell surface, and in the extracellular environment where they interact with various molecules to regulate many cellular processes implicated in health and disease. Subversion of GAGs is a pathogenic strategy shared by a wide variety of microbial pathogens, including viruses, bacteria, parasites, and fungi. Pathogens use GAGs at virtually every major portals of entry to promote their attachment and invasion of host cells, movement from one cell to another, and to protect themselves from immune attack. Pathogens co-opt fundamental activities of GAGs to accomplish these tasks. This ingenious strategy to subvert essential activities of GAGs likely prevented host organisms from deleting or inactivating these mechanisms during their evolution. The goal of this review is to provide a mechanistic overview of our current understanding of how microbes subvert GAGs at major steps of pathogenesis, using select GAG-pathogen interactions as representative examples.",,"['Aquino, Rafael S.', 'Park, Pyong Woo']",,,,
,PMC,Pericardial synovial sarcoma presenting with large recurrent pericardial effusion,http://dx.doi.org/10.21037/jtd.2016.04.57,PMC4885962,,,"Primary pericardial synovial sarcoma is an extremely rare disease with a dismal prognosis. Its main presenting symptoms are a large pericardial effusion, signs of cardiac tamponade, and visualization of a pericardial mass on echocardiography. However, the systemic symptoms of fever, cough, and night sweats may present a clinical picture without any apparent pericardial mass on diagnostic imaging, potentially impeding the diagnosis. We report the case of a 34-year-old patient with fever and recurrent pericardial effusion for 2 years, who was diagnosed with primary pericardial synovial sarcoma after 2-year follow-up echocardiography.",,"['Youn, Hyo Chul', 'Lee, Yangyoun', 'Kim, Soo-Cheol']",,,,
,PMC,Utilizing Nontraditional Data Sources for Near Real-Time Estimation of Transmission Dynamics During the 2015-2016 Colombian Zika Virus Disease Outbreak,http://dx.doi.org/10.2196/publichealth.5814,PMC4909981,27251981,CC BY,"BACKGROUND: Approximately 40 countries in Central and South America have experienced local vector-born transmission of Zika virus, resulting in nearly 300,000 total reported cases of Zika virus disease to date. Of the cases that have sought care thus far in the region, more than 70,000 have been reported out of Colombia. OBJECTIVE: In this paper, we use nontraditional digital disease surveillance data via HealthMap and Google Trends to develop near real-time estimates for the basic (R(0)) and observed (R(obs)) reproductive numbers associated with Zika virus disease in Colombia. We then validate our results against traditional health care-based disease surveillance data. METHODS: Cumulative reported case counts of Zika virus disease in Colombia were acquired via the HealthMap digital disease surveillance system. Linear smoothing was conducted to adjust the shape of the HealthMap cumulative case curve using Google search data. Traditional surveillance data on Zika virus disease were obtained from weekly Instituto Nacional de Salud (INS) epidemiological bulletin publications. The Incidence Decay and Exponential Adjustment (IDEA) model was used to estimate R(0) and R(obs) for both data sources. RESULTS: Using the digital (smoothed HealthMap) data, we estimated a mean R(0) of 2.56 (range 1.42-3.83) and a mean R(obs) of 1.80 (range 1.42-2.30). The traditional (INS) data yielded a mean R(0) of 4.82 (range 2.34-8.32) and a mean R(obs) of 2.34 (range 1.60-3.31). CONCLUSIONS: Although modeling using the traditional (INS) data yielded higher R(0) estimates than the digital (smoothed HealthMap) data, modeled ranges for R(obs) were comparable across both data sources. As a result, the narrow range of possible case projections generated by the traditional (INS) data was largely encompassed by the wider range produced by the digital (smoothed HealthMap) data. Thus, in the absence of traditional surveillance data, digital surveillance data can yield similar estimates for key transmission parameters and should be utilized in other Zika virus-affected countries to assess outbreak dynamics in near real time.",2016 Jun 1,"['Majumder, Maimuna S', 'Santillana, Mauricio', 'Mekaru, Sumiko R', 'McGinnis, Denise P', 'Khan, Kamran', 'Brownstein, John S']",JMIR Public Health Surveill,,,
,PMC,Preparing for Serious Communicable Diseases in the United States: What the Ebola Virus Epidemic Has Taught Us,http://dx.doi.org/10.1128/microbiolspec.EI10-0011-2016,PMC4922497,,,,,"['Varkey, Jay B', 'Ribner, Bruce S']",,,,
,PMC,Recent advances in the production of recombinant subunit vaccines in Pichia pastoris,http://dx.doi.org/10.1080/21655979.2016.1191707,PMC4927204,,,"Recombinant protein subunit vaccines are formulated using defined protein antigens that can be produced in heterologous expression systems. The methylotrophic yeast Pichia pastoris has become an important host system for the production of recombinant subunit vaccines. Although many basic elements of P. pastoris expression system are now well developed, there is still room for further optimization of protein production. Codon bias, gene dosage, endoplasmic reticulum protein folding and culture condition are important considerations for improved production of recombinant vaccine antigens. Here we comment on current advances in the application of P. pastoris for the synthesis of recombinant subunit vaccines.",,"['Wang, Man', 'Jiang, Shuai', 'Wang, Yefu']",,,,
,PMC,Human Metapneumovirus Infections in Hematopoietic Cell Transplant Recipients and Hematologic Malignancy Patients: A Systematic Review,http://dx.doi.org/10.1016/j.canlet.2016.05.035,PMC4935561,,,"Over the past decade, reported incidence of human metapneumovirus (hMPV) has increased owing to the use of molecular assays for diagnosis of respiratory viral infections in cancer patients. The seasonality of these infections, differences in sampling strategies across institutions, and small sample size of published studies make it difficult to appreciate the true incidence and impact of hMPV infections. In this systematic review, we summarized the published data on hMPV infections in hematopoietic cell transplant recipients and patients with hematologic malignancy, focusing on incidence, hMPV-associated lower respiratory tract infection (LRTI), mortality, prevention, and management with ribavirin and/or intravenous immunoglobulins. Although the incidence of hMPV infections and hMPV-associated LRTI in this patient population is similar to respiratory syncytial virus or parainfluenza virus and despite lack of directed antiviral therapy, the mortality rate remains low unless patients develop LRTI. In the absence of vaccine to prevent hMPV, infection control measures are recommended to reduce its burden in cancer patients.",,"['Shah, Dimpy P.', 'Shah, Pankil K.', 'Azzi, Jacques M.', 'El Chaer, Firas', 'Chemaly, Roy F.']",,,,
,PMC,"lncRHOXF1, a Long Noncoding RNA from the X Chromosome That Suppresses Viral Response Genes during Development of the Early Human Placenta",http://dx.doi.org/10.1128/MCB.01098-15,PMC4907097,,,"Long noncoding RNAs (lncRNAs) can regulate gene expression in a cell-specific fashion during development. Here, we identify a novel lncRNA from the X chromosome that we named lncRHOXF1 and which is abundantly expressed in trophectoderm and primitive endoderm cells of human blastocyst-stage embryos. lncRHOXF1 is a spliced and polyadenylated lncRNA about 1 kb in length that is found in both the nuclear and cytoplasmic compartments of in vitro differentiated human trophectoderm progenitor cells. Gain-of-function experiments in human embryonic stem cells, which normally lack lncRHOXF1 RNA, revealed that lncRHOXF1 reduced proliferation and favored cellular differentiation. lncRHOXF1 knockdown using small interfering RNAs (siRNAs) in human trophectoderm progenitors increased expression of viral response genes, including type I interferon. Sendai virus infection of human trophectoderm progenitor cells increased lncRHOXF1 RNA levels, and siRNA-mediated disruption of lncRHOXF1 during infection reduced the expression of viral response genes leading to higher virus replication. Thus, lncRHOXF1 RNA is the first example of a lncRNA that regulates the host response to viral infections in human placental progenitor cells, and we propose that it functions as a repressor of the viral response during early human development.",,"['Penkala, Ian', 'Wang, Jianle', 'Syrett, Camille M.', 'Goetzl, Laura', 'López, Carolina B.', 'Anguera, Montserrat C.']",,,,
,PMC,PNAS Plus Significance Statements,http://dx.doi.org/10.1073/pnas.ss11322,PMC4896707,,,,,,,,,
,PMC,(+) RNA virus replication compartments: a safe home for (most) viral replication,http://dx.doi.org/10.1016/j.mib.2016.05.003,PMC4983521,,,This review describes recent advances in our understanding of the mechanisms by which (+) RNA viruses establish their replication niche.,,"['Shulla, Ana', 'Randall, Glenn']",,,,
,PMC,Rapid induction and persistence of paracrine-induced cellular antiviral states arrest viral infection spread in A549 cells,http://dx.doi.org/10.1016/j.virol.2016.05.019,PMC5159750,,,"The virus/host interaction is a complex interplay between pro- and anti-viral factors that ultimately determines the spread or halt of virus infections in tissues. This interplay develops over multiple rounds of infection. The purpose of this study was to determine how cellular-level processes combine to impact the spatial spread of infection. We measured the kinetics of virus replication (VSV), antiviral paracrine signal upregulation and secretion, spatial spread of virus and paracrine antiviral signaling, and inhibition of virus production in antiviral-exposed A549 human lung epithelial cells. We found that initially infected cells released antiviral signals 4-to-7 hours following production of virus. However, the subsequent rapid dissemination of signal and fast induction of a robust and persistent antiviral state ultimately led to a suppression of infection spread. This work shows how cellular responses to infection and activation of antiviral responses can integrate to ultimately control infection spread across host cell populations.",,"['Voigt, Emily A', 'Swick, Adam', 'Yin, John']",,,,
,PMC,A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection,http://dx.doi.org/10.1016/j.bbagen.2016.05.033,PMC4949077,,,"BACKGROUND: Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant human disease and mortality in the tropics and subtropics. By examining the effects of virus infection on gene expression, and interactions between virus and vector, new targets for prevention of infection and novel treatments may be identified in mosquitoes. We previously performed a microarray analysis of the Ae. aegypti transcriptome during infection with DENV and found that mosquito ubiquitin protein Ub3881 (AAEL003881) was specifically and highly down-regulated. Ubiquitin proteins have multiple functions in insects, including marking proteins for proteasomal degradation, regulating apoptosis and mediating innate immune signaling. METHODS: We used qRT-PCR to quantify gene expression and infection, and RNAi to reduce Ub3881 expression. Mosquitoes were infected with DENV through blood feeding. We transfected DENV protein expression constructs to examine the effect of Ub3881 on protein degradation. We used site-directed mutagenesis and transfection to determine what amino acids are involved in Ub3881-mediated protein degradation. Immunofluorescence, Co-immunoprecipitation and Western blotting were used to examine protein interactions and co-localization. RESULTS: The overexpression of Ub3881, but not related ubiquitin proteins, decreased DENV infection in mosquito cells and live Ae. aegypti. The Ub3881 protein was demonstrated to be involved in DENV envelope protein degradation and reduce the number of infectious virions released. CONCLUSIONS: We conclude that Ub3881 has several antiviral functions in the mosquito, including specific viral protein degradation. GENERAL SIGNIFICANCE: Our data highlights Ub3881 as a target for future DENV prevention strategies in the mosquito transmission vector.",,"['Troupin, Andrea', 'Londono-Renteria, Berlin', 'Conway, Michael J', 'Cloherty, Erin', 'Jameson, Samuel', 'Higgs, Stephen', 'Vanlandingham, Dana L.', 'Fikrig, Erol', 'Colpitts, Tonya M']",,,,
,PMC,Ranking Protein-Protein Docking Results using Steered Molecular Dynamics and Potential of Mean Force Calculations,http://dx.doi.org/10.1002/jcc.24412,PMC5015890,,,"Crystallization of protein-protein complexes can often be problematic and therefore computational structural models are often relied upon. Such models are often generated using protein-protein docking algorithms, where one of the main challenges is selecting which of several thousand potential predictions represents the most near-native complex. We have developed a novel technique that involves the use of steered molecular dynamics (sMD) and umbrella sampling to identify near-native complexes among protein-protein docking predictions. Using this technique, we have found a strong correlation between our predictions and the interface RMSD (iRMSD) in ten diverse test systems. On two of the systems, we investigated if the prediction results could be further improved using potential of mean force calculations. We demonstrated that a near-native (<2.0 Å iRMSD) structure could be identified in the top-1 ranked position for both systems.",,"['Kingsley, Laura J.', 'Esquivel-Rodríguez, Juan', 'Yang, Ying', 'Kihara, Daisuke', 'Lill, Markus A.']",,,,
,PMC,Dynamic Nucleolar Targeting of Dengue Virus Polymerase NS5 in Response to Extracellular pH,http://dx.doi.org/10.1128/JVI.02727-15,PMC4886796,,,"The nucleolar subcompartment of the nucleus is increasingly recognized as an important target of RNA viruses. Here we document for the first time the ability of dengue virus (DENV) polymerase, nonstructural protein 5 (NS5), to accumulate within the nucleolus of infected cells and to target green fluorescent protein (GFP) to the nucleolus of live transfected cells. Intriguingly, NS5 exchange between the nucleus and nucleolus is dynamically modulated by extracellular pH, responding rapidly and reversibly to pH change, in contrast to GFP alone or other nucleolar and non-nucleolar targeted protein controls. The minimal pH-sensitive nucleolar targeting region (pHNTR), sufficient to target GFP to the nucleolus in a pH-sensitive fashion, was mapped to NS5 residues 1 to 244, with mutation of key hydrophobic residues, Leu-165, Leu-167, and Val-168, abolishing pHNTR function in NS5-transfected cells, and severely attenuating DENV growth in infected cells. This is the first report of a viral protein whose nucleolar targeting ability is rapidly modulated by extracellular stimuli, suggesting that DENV has the ability to detect and respond dynamically to the extracellular environment. IMPORTANCE Infections by dengue virus (DENV) threaten 40% of the world's population yet there is no approved vaccine or antiviral therapeutic to treat infections. Understanding the molecular details that govern effective viral replication is key for the development of novel antiviral strategies. Here, we describe for the first time dynamic trafficking of DENV nonstructural protein 5 (NS5) to the subnuclear compartment, the nucleolus. We demonstrate that NS5's targeting to the nucleolus occurs in response to acidic pH, identify the key amino acid residues within NS5 that are responsible, and demonstrate that their mutation severely impairs production of infectious DENV. Overall, this study identifies a unique subcellular trafficking event and suggests that DENV is able to detect and respond dynamically to environmental changes.",,"['Fraser, Johanna E.', 'Rawlinson, Stephen M.', 'Heaton, Steven M.', 'Jans, David A.']",,,,
,PMC,Identification of the Fusion Peptide-Containing Region in Betacoronavirus Spike Glycoproteins,http://dx.doi.org/10.1128/JVI.00015-16,PMC4886789,,,"The fusion peptides (FP) play an essential role in fusion of viral envelope with cellular membranes. The location and properties of the FPs in the spike (S) glycoproteins of different coronaviruses (CoV) have not yet been determined. Through amino acid sequence analysis of S proteins of representative CoVs, we identified a common region as a possible FP (pFP) that shares the characteristics of FPs of class I viral fusion proteins, including high Ala/Gly content, intermediate hydrophobicity, and few charged residues. To test the hypothesis that this region contains the CoV FP, we systemically mutated every residue in the pFP of Middle East respiratory syndrome betacoronavirus (MERS-CoV) and found that 11 of the 22 residues in the pFP (from G953 to L964, except for A956) were essential for S protein-mediated cell-cell fusion and virus entry. The synthetic MERS-CoV pFP core peptide ((955)IAGVGWTAGL(964)) induced extensive fusion of liposome membranes, while mutant peptide failed to induce any lipid mixing. We also selectively mutated residues in pFPs of two other β-CoVs, severe acute respiratory syndrome coronavirus (SARS-CoV) and mouse hepatitis virus (MHV). Although the amino acid sequences of these two pFPs differed significantly from that of MERS-CoV and each other, most of the pFP mutants of SARS-CoV and MHV also failed to mediate membrane fusion, suggesting that these pFPs are also the functional FPs. Thus, the FPs of 3 different lineages of β-CoVs are conserved in location within the S glycoproteins and in their functions, although their amino acid sequences have diverged significantly during CoV evolution. IMPORTANCE Within the class I viral fusion proteins of many enveloped viruses, the FP is the critical mediator of fusion of the viral envelope with host cell membranes leading to virus infection. FPs from within a virus family, like influenza viruses or human immunodeficiency viruses (HIV), tend to share high amino acid sequence identity. In this study, we determined the location and amino acid sequences of the FPs of S glycoproteins of 3 β-CoVs, MERS-CoV, SARS-CoV, and MHV, and demonstrated that they were essential for mediating cell-cell fusion and virus entry. Interestingly, in marked contrast to the FPs of influenza and HIV, the primary amino acid sequences of the FPs of β-CoVs in 3 different lineages differed significantly. Thus, during evolution the FPs of β-CoVs have diverged significantly in their primary sequences while maintaining the same essential biological functions. Our findings identify a potential new target for development of drugs against CoVs.",,"['Ou, Xiuyuan', 'Zheng, Wangliang', 'Shan, Yiwei', 'Mu, Zhixia', 'Dominguez, Samuel R.', 'Holmes, Kathryn V.', 'Qian, Zhaohui']",,,,
,PMC,Delta inulin-derived adjuvants that elicit Th1 phenotype following vaccination reduces respiratory syncytial virus lung titers without a reduction in lung immunopathology,http://dx.doi.org/10.1080/21645515.2016.1162931,PMC4994749,,,"Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract infections resulting in bronchiolitis and even mortality in the elderly and young children/infants. Despite the impact of this virus on human health, no licensed vaccine exists. Unlike many other viral infections, RSV infection or vaccination does not induce durable protective antibodies in humans. In order to elicit high titer, neutralizing antibodies against RSV, we investigated the use of the adjuvant Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles, to enhance antibody titers following vaccination. BALB/c mice were vaccinated intramuscularly with live RSV as a vaccine antigen in combination with one of two formulations of Advax™. Advax-1 was comprised of the standard delta inulin adjuvant and Advax-2 was formulated delta inulin plus CpG oligodendronucleotides (ODNs). An additional group of mice were either mock vaccinated, immunized with vaccine only, or administered vaccine plus Imject Alum. Following 3 vaccinations, mice had neutralizing antibody titers that correlated with reduction in viral titers in the lungs. Advax-1 significantly enhanced serum RSV-specific IgG1 levels at week 6 indicative of a Th2 response, similar to titers in mice administered vaccine plus Imject Alum. In contrast, mice vaccinated with vaccine plus Advax-2 had predominately IgG2a titers indicative of a Th1 response that was maintained during the entire study. Interestingly, regardless of which Advax(TM) adjuvant was used, the neutralizing titers were similar between groups, but the viral lung titers were significantly lower (∼10E+3pfu/g) in mice administered vaccine with either Advax(TM) adjuvant compared to mice administered adjuvants only. The lung pathology in vaccinated mice with Advax(TM) was similar to Imject Alum. Overall, RSV vaccine formulated with Advax(TM) had high neutralizing antibody titers with low lung viral titers, but exacerbated lung pathology compared to unvaccinated mice.",,"['Wong, Terianne M.', 'Petrovsky, Nikolai', 'Bissel, Stephanie J.', 'Wiley, Clayton A.', 'Ross, Ted M.']",,,,
,PMC,Long-term persistence of donor alveolar macrophages in human lung transplant recipients that influences donor specific immune responses,http://dx.doi.org/10.1111/ajt.13819,PMC5289407,,,"Steady state alveolar macrophages (AM) are long-lived lung-resident macrophages with sentinel function. Evidence suggests that AM precursors originate during embryogenesis and populate lungs without replenishment by circulating leukocytes. However, their presence and persistence are unclear following human lung transplantation (LTx). Our goal was to examine donor AM longevity and evaluate whether AM of recipient origin seeds the transplanted lungs. Origin of AM was accessed using donor-recipient HLA mismatches. We demonstrate that 94–100% of AM present in bronchoalveolar lavage (BAL) were donor derived and importantly AM of recipient origin were not detected. Further, analysis of BAL cells up to 3.5 yrs post-LTx revealed that majority of AM (>87%) was donor derived. Elicitation of de novo donor specific antibody (DSA) is a major post-LTx complication and a risk factor for development of chronic rejection. The donor AM responded to anti-HLA framework Ab with secretion of inflammatory cytokines. Further, in an experimental murine model, we demonstrate that adoptive transfer of allogeneic AM stimulated humoral and cellular immune responses to alloantigen and lung-associated self-antigens and led to bronchiolar obstruction. Therefore, donor derived AM play an essential role in the DSA induced inflammatory cascade leading to obliterative airway disease of the transplanted lungs.",,"['Nayak, D.K.', 'Zhou, F.', 'Xu, M.', 'Huang, J.', 'Tsuji, M.', 'Hachem, R.', 'Mohanakumar, T.']",,,,
,PMC,Structural and Functional Characterization of Programmed Ribosomal Frameshift Signals in West Nile Virus Strains Reveals High Structural Plasticity Among cis-Acting RNA Elements,http://dx.doi.org/10.1074/jbc.M116.735613,PMC4957060,,,"West Nile virus (WNV) is a prototypical emerging virus for which no effective therapeutics currently exist. WNV uses programmed −1 ribosomal frameshifting (−1 PRF) to synthesize the NS1′ protein, a C terminally extended version of its non-structural protein 1, the expression of which enhances neuro-invasiveness and viral RNA abundance. Here, the NS1′ frameshift signals derived from four WNV strains were investigated to better understand −1 PRF in this quasispecies. Sequences previously predicted to promote −1 PRF strongly promote this activity, but frameshifting was significantly more efficient upon inclusion of additional 3′ sequence information. The observation of different rates of −1 PRF, and by inference differences in the expression of NS1′, may account for the greater degrees of pathogenesis associated with specific WNV strains. Chemical modification and mutational analyses of the longer and shorter forms of the −1 PRF signals suggests dynamic structural rearrangements between tandem stem-loop and mRNA pseudoknot structures in two of the strains. A model is suggested in which this is employed as a molecular switch to fine tune the relative expression of structural to non-structural proteins during different phases of the viral replication cycle.",,"['Moomau, Christine', 'Musalgaonkar, Sharmishtha', 'Khan, Yousuf A.', 'Jones, John E.', 'Dinman, Jonathan D.']",,,,
,PMC,Dual Roles of Group IID Phospholipase A(2) in Inflammation and Cancer,http://dx.doi.org/10.1074/jbc.M116.734624,PMC4957044,,,"Phospholipase A(2) enzymes have long been implicated in the promotion of inflammation by mobilizing pro-inflammatory lipid mediators, yet recent evidence suggests that they also contribute to anti-inflammatory or pro-resolving programs. Group IID-secreted phospholipase A(2) (sPLA(2)-IID) is abundantly expressed in dendritic cells in lymphoid tissues and resolves the Th1 immune response by controlling the steady-state levels of anti-inflammatory lipids such as docosahexaenoic acid and its metabolites. Here, we show that psoriasis and contact dermatitis were exacerbated in Pla2g2d-null mice, whereas they were ameliorated in Pla2g2d-overexpressing transgenic mice, relative to littermate wild-type mice. These phenotypes were associated with concomitant alterations in the tissue levels of ω3 polyunsaturated fatty acid (PUFA) metabolites, which had the capacity to reduce the expression of pro-inflammatory and Th1/Th17-type cytokines in dendritic cells or lymph node cells. In the context of cancer, however, Pla2g2d deficiency resulted in marked attenuation of skin carcinogenesis, likely because of the augmented anti-tumor immunity. Altogether, these results underscore a general role of sPLA(2)-IID as an immunosuppressive sPLA(2) that allows the microenvironmental lipid balance toward an anti-inflammatory state, exerting beneficial or detrimental impact depending upon distinct pathophysiological contexts in inflammation and cancer.",,"['Miki, Yoshimi', 'Kidoguchi, Yuh', 'Sato, Mariko', 'Taketomi, Yoshitaka', 'Taya, Choji', 'Muramatsu, Kazuaki', 'Gelb, Michael H.', 'Yamamoto, Kei', 'Murakami, Makoto']",,,,
,PMC,Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design,http://dx.doi.org/10.1146/annurev-immunol-041015-055515,PMC6034635,,,"HIV employs multiple means to evade the humoral immune response, particularly the elicitation of and recognition by broadly neutralizing antibodies (bnAbs). Such antibodies can act antivirally against a wide spectrum of viruses by targeting relatively conserved regions on the surface HIV envelope trimer spike. Elicitation of and recognition by bnAbs are hindered by the arrangement of spikes on virions and the relatively difficult access to bnAb epitopes on spikes, including the proximity of variable regions and a high density of glycans. Yet, in a small proportion of HIV-infected individuals, potent bnAb responses do develop, and isolation of the corresponding monoclonal antibodies has been facilitated by identification of favorable donors with potent bnAb sera and by development of improved methods for human antibody generation. Molecular studies of recombinant Env trimers, alone and in interaction with bnAbs, are providing new insights that are fueling the development and testing of promising immunogens aimed at the elicitation of bnAbs.",,"['Burton, Dennis R.', 'Hangartner, Lars']",,,,
,PMC,"Kinetic, Mutational, and Structural Studies of the Venezuelan Equine Encephalitis Virus Nonstructural Protein 2 Cysteine Protease",http://dx.doi.org/10.1021/acs.biochem.5b00992,PMC5290728,,,"The Venezuelan equine encephalitis virus (VEEV) nonstructural protein 2 (nsP2) cysteine protease (EC 3.4.22.-) is essential for viral replication and is involved in the cytopathic effects (CPE) of the virus. The VEEV nsP2 protease is a member of MEROPS Clan CN and characteristically contains a papain-like protease linked to an S-adenosyl-L-methionine dependent RNA methyltransferase (SAM MTase) domain. The protease contains an alternative active site motif, (475)NVCWAK(480), which differs from papain’s (CGS(25)CWAFS), and the enzyme lacks a transition state (TS) stabilizing residue homologous to Q19 in papain. To understand the roles of conserved residues in catalysis we determined the structure of the free enzyme, and the first structure of an inhibitor-bound alphaviral protease. The peptide-like E64d inhibitor was found to bind beneath a β-hairpin at the interface of the SAM MTase and protease domains. His-546 adopted a conformation that differed from that found in the free enzyme, each conformer may assist in leaving group departure of either the amine or Cys thiolate during the catalytic cycle. Interestingly, E64c (200 μM), the carboxylic acid form of the E64d ester, did not inhibit the nsP2 protease. To identify key residues involved in substrate binding, a number of mutants were analyzed. Mutation of the motif residue, N475A, led to a 24-fold reduction in k(cat)/K(m), and the conformation of this residue did not change after inhibition. N475 forms a hydrogen bond with R662 in the SAM MTase domain, and the R662A and R662K mutations both led to 16-fold reductions in k(cat)/K(m). N475 forms the base of the P1 binding site and likely orients the substrate for nucleophilic attack or plays a role in product release. An Asn homologous to N475 is similarly found in coronaviral papain-like proteases (PLpro) of the Severe Acute Respiratory Syndrome (SARS) virus and Middle Eastern Respiratory virus (MERS). Mutation of another motif residue, K480A, led to a 9-fold decrease in k(cat) and k(cat)/K(m). K480 likely enhances the nucleophilicity of the Cys. Consistent with our substrate-bound models, the SAM MTase domain K706A mutation increased the K(m) 4.5-fold to 500 μM. Within the β-hairpin, the N545A mutation slightly, but not significantly increased the k(cat) and K(m). The structures and identified active site residues may facilitate the discovery of protease inhibitors with antiviral activity.",,"['Hu, Xin', 'Compton, Jaimee R.', 'Leary, Dagmar H.', 'Olson, Mark A.', 'Lee, Michael S.', 'Cheung, Jonah', 'Ye, Wenjuan', 'Ferrer, Mark', 'Southall, Noel', 'Jadhav, Ajit', 'Glass, Pamela J.', 'Marugan, Juan', 'Legler, Patricia M.']",,,,
,PMC,Recognition of Lys48-linked di-ubiquitin and deubiquitinating activities of the SARS coronavirus papain-like protease,http://dx.doi.org/10.1016/j.molcel.2016.04.016,PMC4875570,,,"Deubiquitinating enzymes (DUBs) recognize and cleave linkage-specific poly-ubiquitin (polyUb) chains, but mechanisms underlying specificity remain elusive in many cases. The Severe Acute Respiratory Syndrome (SARS) coronavirus papain-like protease (PLpro) is a DUB that cleaves ISG15, a two domain Ub-like protein, and Lys48-linked polyUb chains, releasing diUb(Lys48) products. To elucidate this specificity, we report the 2.85 Å crystal structure of SARS PLpro bound to a diUb(Lys48) activity-based probe. SARS PLpro binds diUb(Lys48) in an extended conformation via two contact sites, S1 and S2, which are proximal and distal to the active site, respectively. We show that specificity for polyUb(Lys48) chains is predicated on contacts in the S2 site and enhanced by an S1–S1′ preference for a Lys48 linkage across the active site. In contrast, ISG15 specificity is dominated by contacts in the S1 site. Determinants revealed for polyUb(Lys48) specificity should prove useful in understanding PLpro deubiquitinating activities in coronavirus infections.",,"['Békés, Miklós', 'van der Heden van Noort, Gerbrand J.', 'Ekkebus, Reggy', 'Ovaa, Huib', 'Huang, Tony T.', 'Lima, Christopher D.']",,,,
,PMC,Constitutive IFNα/β signaling maintains expression of signaling intermediaries for efficient cytokine responses,http://dx.doi.org/10.1080/21623996.2016.1173804,PMC4964971,,,"Interferons (IFNs) are a family of immunoregulatory cytokines with important roles in anti-viral and anti-tumor responses. Type I and II IFNs bind distinct receptors and are associated with different stages of the immune response. There is however, considerable crosstalk between these two cytokines with enhancement of IFNγ responses following IFNα/β priming and loss of IFNα/β receptor (IFNAR) resulting in diminished IFNγ responses. In this study, we sought to define the mechanism of crosstalk between the type I and II IFNs. Our previous reports demonstrated reduced expression of the canonically activated transcription factor signal transducer and activator of transcription (STAT)1, in cells lacking the IFNAR α chain (IFNAR1). Therefore, we used microarray analysis to determine whether reconstitution of STAT1 in IFNAR1-deficient cells was sufficient to restore IFNγ responses. We identified several biological pathways, including the MHC class I antigen presentation pathway, in which STAT1 reconstitution was able to significantly rescue IFNγ-mediated gene regulation in Ifnar1(−/−) cells. Notably, we also found that in addition to low basal expression of STAT1, cells lacking the IFNAR1 also had aberrant expression of multiple other transcription factors and signaling intermediaries. The studies described herein demonstrate that basal and regulated expression of signaling intermediaries is a mechanism for crosstalk between cytokines including type I and II IFNs.",,"['Messina, Nicole L.', 'Clarke, Christopher J. P.', 'Johnstone, Ricky W.']",,,,
,PMC,Blood group A and Rh(D)-negativity are associated with symptomatic West Nile virus infection,http://dx.doi.org/10.1111/trf.13622,PMC4938756,,,"BACKGROUND: West Nile virus (WNV) infection is mostly asymptomatic but 20% of subjects report WNV fever and 1% of patients experience neurological diseases with higher rates in elderly and immunosuppressed persons. With no treatment and no vaccine to prevent the development of symptomatic infections, it is essential to understand prognostic factors influencing symptomatic disease outcome. Host genetic background has been linked to the development of WNV neuroinvasive disease. The present study investigates the association between the ABO and Rh(D) blood group status and WNV disease outcome. STUDY DESIGN AND METHODS: The distribution of blood groups was investigated within a cohort of 374 WNV+ blood donors including 244 asymptomatic (AS) and 130 symptomatic (S) WNV+ blood donors. Logistic regression analyses were used to examine associations between A, B, O and Rh(D) blood groups and WNV clinical disease outcome. RESULTS: Symptomatic WNV+ donors exhibited increased frequencies of blood group A (S 47.6% AS 36.8%, P=0.04, OR [95%CI] 1.56 [1.01–2.40]) and Rh(D)-negative individuals (S 21.5% AS 13.1%, P=0.03, OR [95%CI] 1.82 [1.04–3.18]). CONCLUSION: The findings suggest a genetic susceptibility placing blood group A and Rh(D)-negative individuals at risk for the development of symptomatic disease outcome after WNV infection.",,"['Kaidarova, Zhanna', 'Bravo, Marjorie D.', 'Kamel, Hany T.', 'Custer, Brian S', 'Busch, Michael P.', 'Lanteri, Marion C.']",,,,
,PMC,Profile: Gary Kobinger — “My goal became to prevent death”,http://dx.doi.org/10.1503/cmaj.109-5261,PMC4868602,,,,,"Morin, Véronique",,,,
,PMC,RSV infection without ribavirin treatment in pediatric hematopoietic stem cell transplantation,http://dx.doi.org/10.1038/bmt.2016.124,PMC5693335,,,,,"['El-Bietar, J', 'Nelson, A', 'Wallace, G', 'Dandoy, C', 'Jodele, S', 'Myers, KC', 'Teusink, A', 'Lane, A', 'Davies, SM', 'Danziger-Isakov, L']",,,,
,PMC,Coronavirus receptor switch explained from the stereochemistry of protein–carbohydrate interactions and a single mutation,http://dx.doi.org/10.1073/pnas.1519881113,PMC4896708,,,"Hemagglutinin-esterases (HEs) are bimodular envelope proteins of orthomyxoviruses, toroviruses, and coronaviruses with a carbohydrate-binding “lectin” domain appended to a receptor-destroying sialate-O-acetylesterase (“esterase”). In concert, these domains facilitate dynamic virion attachment to cell-surface sialoglycans. Most HEs (type I) target 9-O-acetylated sialic acids (9-O-Ac-Sias), but one group of coronaviruses switched to using 4-O-Ac-Sias instead (type II). This specificity shift required quasisynchronous adaptations in the Sia-binding sites of both lectin and esterase domains. Previously, a partially disordered crystal structure of a type II HE revealed how the shift in lectin ligand specificity was achieved. How the switch in esterase substrate specificity was realized remained unresolved, however. Here, we present a complete structure of a type II HE with a receptor analog in the catalytic site and identify the mutations underlying the 9-O- to 4-O-Ac-Sia substrate switch. We show that (i) common principles pertaining to the stereochemistry of protein–carbohydrate interactions were at the core of the transition in lectin ligand and esterase substrate specificity; (ii) in consequence, the switch in O-Ac-Sia specificity could be readily accomplished via convergent intramolecular coevolution with only modest architectural changes in lectin and esterase domains; and (iii) a single, inconspicuous Ala-to-Ser substitution in the catalytic site was key to the emergence of the type II HEs. Our findings provide fundamental insights into how proteins “see” sugars and how this affects protein and virus evolution.",,"['Bakkers, Mark J. G.', 'Zeng, Qinghong', 'Feitsma, Louris J.', 'Hulswit, Ruben J. G.', 'Li, Zeshi', 'Westerbeke, Aniek', 'van Kuppeveld, Frank J. M.', 'Boons, Geert-Jan', 'Langereis, Martijn A.', 'Huizinga, Eric G.', 'de Groot, Raoul J.']",,,,
,PMC,Cardiovascular safety of dipeptidyl peptidase-4 inhibitors: recent evidence on heart failure,,PMC4891459,,,"The cardiovascular safety of DPP4 inhibitors as a class, especially in regards to heart failure, has been questioned after the publication of first trials (SAVOR-TIMI 53 and EXAMINE) assessing the cardiovascular risks of DPP4 inhibitors alogliptin and sitagliptin in 2013. Although there were no increased risks in composite cardiovascular outcomes, the SAVOR-TIMI 53 trial reported a 27% increase in hospitalization for heart failure in diabetic patients who received the DPP4 inhibitor saxagliptin. There has been substantial increase in knowledge on the heart failure effect of DPP4 inhibition since 2013. This review will summarize the role of the DPP4/incretin axis in heart failure and discuss the findings from recent large scale clinical trials assessing the effects of DPP4 inhibitors on heart failure.",,"['Kankanala, Saumya Reddy', 'Syed, Rafay', 'Gong, Quan', 'Ren, Boxu', 'Rao, Xiaoquan', 'Zhong, Jixin']",,,,
,PMC,Stress granules at the intersection of autophagy and ALS,http://dx.doi.org/10.1016/j.brainres.2016.05.022,PMC5055418,,,"Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease caused by loss of upper and lower motor neurons. The majority of ALS cases are classified as sporadic (80-90%), with the remaining considered familial based on patient history. The last decade has seen a surge in the identification of ALS-causing genes – including TARDBP (TDP-43), FUS, MATR3 (Matrin-3), C9ORF72 and several others – providing important insights into the molecular pathways involved in pathogenesis. Most of the protein products of ALS-linked genes fall into two functional categories: RNA-binding/homeostasis and protein-quality control (i.e. autophagy and proteasome). The RNA-binding proteins tend to be aggregation-prone with low-complexity domains similar to the prion-forming domains of yeast. Many also incorporate into stress granules (SGs), which are cytoplasmic ribonucleoprotein complexes that form in response to cellular stress. Mutant forms of TDP-43 and FUS perturb SG dynamics, lengthening their cytoplasmic persistence. Recent evidence suggests that SGs are regulated by the autophagy pathway, suggesting a unifying connection between many of the ALS-linked genes. Persistent SGs may give rise to intractable aggregates that disrupt neuronal homeostasis, thus failure to clear SGs by autophagic processes may promote ALS pathogenesis.",,"['Monahan, Zachary', 'Shewmaker, Frank', 'Pandey, Udai Bhan']",,,,
,PMC,Development of a bead-based suspension array for the detection of pathogens in acute respiratory tract infections,http://dx.doi.org/10.1177/1535370216647128,PMC4994910,,,We developed a high-throughput bead-based suspension array for simultaneous detection of 20 respiratory tract pathogens in clinical specimens. Pathogen-specific genes were amplified and hybridized to probes coupled to carboxyl-encoded microspheres. Fluorescence intensities generated via the binding of phycoerythrin-conjugated streptavidin with biotin-labeled targets were measured by the Luminex 100 bead-based suspension array system. The bead-based suspension array detected bacteria in a significantly higher number of samples compared to the conventional culture. There was no significant difference in the detection rate of atypical pathogensatypical pathogens or viruses between the bead-based suspension array and real-time PCR. This technology can play a significant role in screening patients with pneumonia.,,"['Chen, Yu-Sheng', 'Li, Hong-Ru', 'Zhang, Wei', 'Hua, Zhi-Dan', 'Lin, Xiao-Hong', 'Lin, Meng-Qing', 'Huang, Wen-Sen', 'Huang, Li-Ping', 'Yu, Xiao-Li', 'Xu, Neng-Luan', 'Lin, Ming', 'Xie, Bao-Song', 'Shen, Xiao-Na', 'Xie, Jian-Feng', 'Wang, Yi', 'Huang, Meng', 'Wu, Yan-An', 'Hu, Xin-Lan']",,,,
,PMC,MicroRNA-223 Promotes Type I Interferon Production in Antiviral Innate Immunity by Targeting Forkhead Box Protein O3 (FOXO3),http://dx.doi.org/10.1074/jbc.M115.700252,PMC4938189,,,"Effective recognition of viral infection and subsequent triggering of antiviral innate immune responses are essential for the host antiviral defense, which is tightly regulated by multiple regulators, including microRNAs. Previous reports have shown that some microRNAs are induced during virus infection and participate in the regulation of the innate antiviral response. However, whether the type I IFN response is regulated by miR-223 is still unknown. Here, we reported that vesicular stomatitis virus (VSV) infection induced significant up-regulation of miR-223 in murine macrophages. We observed that miR-223 overexpression up-regulated type I IFN expression levels in VSV-infected macrophages. We also demonstrated that miR-223 directly targets FOXO3 to regulate the type I IFN production. Furthermore, type I IFN, which is triggered by VSV infection, is responsible for the up-regulation of miR-223, thus forming a positive regulatory loop for type I IFN production. Our results uncovered a novel mechanism of miR-223-mediated regulation of type I IFN production in the antiviral innate immunity for the first time.",,"['Chen, Luoquan', 'Song, Yinjing', 'He, Li', 'Wan, Xiaopeng', 'Lai, Lihua', 'Dai, Feng', 'Liu, Yang', 'Wang, Qingqing']",,,,
,PMC,Viral evasion of intracellular DNA and RNA sensing,http://dx.doi.org/10.1038/nrmicro.2016.45,PMC5072394,,,"The co-evolution of viruses with their hosts has led to the emergence of viral pathogens that are adept at evading or actively suppressing host immunity. Pattern recognition receptors (PRRs) are key components of antiviral immunity that detect conserved molecular features of viral pathogens and initiate signalling that results in the expression of antiviral genes. In this Review, we discuss the strategies that viruses use to escape immune surveillance by key intracellular sensors of viral RNA or DNA, with a focus on RIG-I-like receptors (RLRs), cyclic GMP–AMP synthase (cGAS) and interferon-γ (IFNγ)-inducible protein 16 (IFI16). Such viral strategies include the sequestration or modification of viral nucleic acids, interference with specific post-translational modifications of PRRs or their adaptor proteins, the degradation or cleavage of PRRs or their adaptors, and the sequestration or relocalization of PRRs. An understanding of viral immune-evasion mechanisms at the molecular level may guide the development of vaccines and antivirals.",,"['Chan, Ying Kai', 'Gack, Michaela U.']",,,,
,PMC,Porcine Reproductive and Respiratory Syndrome Virus Nucleocapsid Protein Interacts with Nsp9 and Cellular DHX9 To Regulate Viral RNA Synthesis,http://dx.doi.org/10.1128/JVI.03216-15,PMC4934760,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid (N) protein is the main component of the viral capsid to encapsulate viral RNA, and it is also a multifunctional protein involved in the regulation of host cell processes. Nonstructural protein 9 (Nsp9) is the RNA-dependent RNA polymerase that plays a critical role in viral RNA transcription and replication. In this study, we demonstrate that PRRSV N protein is bound to Nsp9 by protein-protein interaction and that the contacting surface on Nsp9 is located in the two predicted α-helixes formed by 48 residues at the C-terminal end of the protein. Mutagenesis analyses identified E646, E608, and E611 on Nsp9 and Q85 on the N protein as the pivotal residues participating in the N-Nsp9 interaction. By overexpressing the N protein binding fragment of Nsp9 in infected Marc-145 cells, the synthesis of viral RNAs, as well as the production of infectious progeny viruses, was dramatically inhibited, suggesting that Nsp9-N protein association is involved in the process of viral RNA production. In addition, we show that PRRSV N interacts with cellular RNA helicase DHX9 and redistributes the protein into the cytoplasm. Knockdown of DHX9 increased the ratio of short subgenomic mRNAs (sgmRNAs); in contrast, DHX9 overexpression benefited the synthesis of longer sgmRNAs and the viral genomic RNA (gRNA). These results imply that DHX9 is recruited by the N protein in PRRSV infection to regulate viral RNA synthesis. We postulate that N and DHX9 may act as antiattenuation factors for the continuous elongation of nascent transcript during negative-strand RNA synthesis. IMPORTANCE It is unclear whether the N protein of PRRSV is involved in regulation of the viral RNA production process. In this report, we demonstrate that the N protein of the arterivirus PRRSV participates in viral RNA replication and transcription through interacting with Nsp9 and its RdRp and recruiting cellular RNA helicase to promote the production of longer viral sgmRNAs and gRNA. Our data here provide some new insights into the discontinuous to continuous extension of PRRSV RNA synthesis and also offer a new potential anti-PRRSV strategy targeting the N-Nsp9 and/or N-DHX9 interaction.",,"['Liu, Long', 'Tian, Jiao', 'Nan, Hao', 'Tian, Mengmeng', 'Li, Yuan', 'Xu, Xiaodong', 'Huang, Baicheng', 'Zhou, Enmin', 'Hiscox, Julian A.', 'Chen, Hongying']",,,,
,PMC,Mutagenesis of Coronavirus nsp14 Reveals Its Potential Role in Modulation of the Innate Immune Response,http://dx.doi.org/10.1128/JVI.03259-15,PMC4934755,,,"Coronavirus (CoV) nonstructural protein 14 (nsp14) is a 60-kDa protein encoded by the replicase gene that is part of the replication-transcription complex. It is a bifunctional enzyme bearing 3′-to-5′ exoribonuclease (ExoN) and guanine-N7-methyltransferase (N7-MTase) activities. ExoN hydrolyzes single-stranded RNAs and double-stranded RNAs (dsRNAs) and is part of a proofreading system responsible for the high fidelity of CoV replication. nsp14 N7-MTase activity is required for viral mRNA cap synthesis and prevents the recognition of viral mRNAs as “non-self” by the host cell. In this work, a set of point mutants affecting different motifs within the ExoN domain of nsp14 was generated, using transmissible gastroenteritis virus as a model of Alphacoronavirus. Mutants lacking ExoN activity were nonviable despite being competent in both viral RNA and protein synthesis. A specific mutation within zinc finger 1 (ZF-C) led to production of a viable virus with growth and viral RNA synthesis kinetics similar to that of the parental virus. Mutant recombinant transmissible gastroenteritis virus (TGEV) ZF-C (rTGEV-ZF-C) caused decreased cytopathic effect and apoptosis compared with the wild-type virus and reduced levels of dsRNA accumulation at late times postinfection. Consequently, the mutant triggered a reduced antiviral response, which was confirmed by evaluating different stages of the dsRNA-induced antiviral pathway. The expression of beta interferon (IFN-β), tumor necrosis factor (TNF), and interferon-stimulated genes in cells infected with mutant rTGEV-ZF-C was reduced compared to the levels seen with the parental virus. Overall, our data revealed a potential role for CoV nsp14 in modulation of the innate immune response. IMPORTANCE The innate immune response is the first line of antiviral defense that culminates in the synthesis of interferon and proinflammatory cytokines to control viral replication. CoVs have evolved several mechanisms to counteract the innate immune response at different levels, but the role of CoV-encoded ribonucleases in preventing activation of the dsRNA-induced antiviral response has not been described to date. The introduction of a mutation in zinc finger 1 of the ExoN domain of nsp14 led to production of a virus that induced a weak antiviral response, most likely due to the accumulation of lower levels of dsRNA in the late phases of infection. These observations allowed us to propose a novel role for CoV nsp14 ExoN activity in counteracting the antiviral response, which could serve as a novel target for the design of antiviral strategies.",,"['Becares, Martina', 'Pascual-Iglesias, Alejandro', 'Nogales, Aitor', 'Sola, Isabel', 'Enjuanes, Luis', 'Zuñiga, Sonia']",,,,
,PMC,Mapping the Specific Amino Acid Residues That Make Hamster DPP4 Functional as a Receptor for Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.03267-15,PMC4934753,,,"The novel emerging coronavirus Middle East respiratory syndrome coronavirus (MERS-CoV) binds to its receptor, dipeptidyl peptidase 4 (DPP4), via 14 interacting amino acids. We previously showed that if the five interacting amino acids which differ between hamster and human DPP4 are changed to the residues found in human DPP4, hamster DPP4 does act as a receptor. Here, we show that the functionality of hamster DPP4 as a receptor is severely decreased if less than 4 out of 5 amino acids are changed. IMPORTANCE The novel emerging coronavirus MERS-CoV has infected >1,600 people worldwide, and the case fatality rate is ∼36%. In this study, we show that by changing 4 amino acids in hamster DPP4, this protein functions as a receptor for MERS-CoV. This work is vital in the development of new small-animal models, which will broaden our understanding of MERS-CoV and be instrumental in the development of countermeasures.",,"['van Doremalen, Neeltje', 'Miazgowicz, Kerri L.', 'Munster, Vincent J.']",,,,
,PMC,Defensins at the Mucosal Surface: Latest Insights into Defensin-Virus Interactions,http://dx.doi.org/10.1128/JVI.00904-15,PMC4934752,,,"Defensins are innate immune effector peptides expressed at mucosal surfaces throughout the human body and are potently antiviral in vitro. The role of defensins in viral pathogenesis in vivo is poorly understood; however, recent studies have revealed that defensin-virus interactions in vivo are complicated and distinct from their proposed antiviral mechanisms in vitro. These findings highlight the need for additional research that connects defensin neutralization of viruses in cell culture to in vivo antiviral mechanisms.",,"['Wilson, Sarah S.', 'Wiens, Mayim E.', 'Holly, Mayumi K.', 'Smith, Jason G.']",,,,
,PMC,Inflammatory and oxidative stress in rotavirus infection,http://dx.doi.org/10.5501/wjv.v5.i2.38,PMC4861870,,,"Rotaviruses are the single leading cause of life-threatening diarrhea affecting children under 5 years of age. Rotavirus entry into the host cell seems to occur by sequential interactions between virion proteins and various cell surface molecules. The entry mechanisms seem to involve the contribution of cellular molecules having binding, chaperoning and oxido-reducing activities. It appears to be that the receptor usage and tropism of rotaviruses is determined by the species, cell line and rotavirus strain. Rotaviruses have evolved functions which can antagonize the host innate immune response, whereas are able to induce endoplasmic reticulum (ER) stress, oxidative stress and inflammatory signaling. A networking between ER stress, inflammation and oxidative stress is suggested, in which release of calcium from the ER increases the generation of mitochondrial reactive oxygen species (ROS) leading to toxic accumulation of ROS within ER and mitochondria. Sustained ER stress potentially stimulates inflammatory response through unfolded protein response pathways. However, the detailed characterization of the molecular mechanisms underpinning these rotavirus-induced stressful conditions is still lacking. The signaling events triggered by host recognition of virus-associated molecular patterns offers an opportunity for the development of novel therapeutic strategies aimed at interfering with rotavirus infection. The use of N-acetylcysteine, non-steroidal anti-inflammatory drugs and PPARγ agonists to inhibit rotavirus infection opens a new way for treating the rotavirus-induced diarrhea and complementing vaccines.",,"['Guerrero, Carlos A', 'Acosta, Orlando']",,,,
,PMC,The International Health Regulations: The Governing Framework for Global Health Security,http://dx.doi.org/10.1111/1468-0009.12186,PMC4911720,,,"POLICY POINTS: The International Health Regulations (IHR) are the governing framework for global health security yet require textual and operational reforms to remain effective, particularly as parallel initiatives are developed. The World Health Organization (WHO) is the agency charged with oversight of the IHR, and its leadership and efficient functioning are prerequisites for the effective implementation of the IHR. We reviewed the historical origins of the IHR and their performance over the past 10 years and analyzed all of the ongoing reform panel efforts to provide a series of politically feasible recommendations for fundamental reform. This article offers proposals for fundamental reform—with politically feasible pathways—of the IHR, their operations and implementation, WHO oversight, and State Party conformance. CONTEXT: The International Health Regulations (IHR) have been the governing framework for global health security for the past decade and are a nearly universally recognized World Health Organization (WHO) treaty, with 196 States Parties. In the wake of the Ebola epidemic, major global commissions have cast doubt on the future effectiveness of the IHR and the leadership of the WHO. METHODS: We conducted a review of the historical origins of the IHR and their performance over the past 10 years and analyzed all of the ongoing reform panel efforts to provide a series of politically feasible recommendations for fundamental reform. FINDINGS: We propose a series of recommendations with realistic pathways for change. These recommendations focus on the development and strengthening of IHR core capacities; independently assessed metrics; new financing mechanisms; harmonization with the Global Health Security Agenda, Performance of Veterinary Services (PVS) Pathways, the Pandemic Influenza Preparedness Framework, and One Health strategies; public health and clinical workforce development; Emergency Committee transparency and governance; tiered public health emergency of international concern (PHEIC) processes; enhanced compliance mechanisms; and an enhanced role for civil society. CONCLUSIONS: Empowering the WHO and realizing the IHR's potential will shore up global health security—a vital investment in human and animal health—while reducing the vast economic consequences of the next global health emergency.",,"['GOSTIN, LAWRENCE O.', 'KATZ, REBECCA']",,,,
,PMC,The Dual Complexity of PTX3 in Health and Disease: A Balancing Act?,http://dx.doi.org/10.1016/j.molmed.2016.04.007,PMC5414840,,,"The humoral arm of innate immunity is complex and includes various molecules that serve as markers of inflammation with complementary characteristics, such as the short pentraxins C reactive protein (CRP), Serum Amyloid P (SAP) and the long pentraxin, PTX3. There is a growing amount of evidence — including mouse and human genetics — that suggests that PTX3 is essential in conferring host resistance against selected pathogens and moreover, that it plays a dual antagonistic role in the regulation of inflammation. Dissection of such a yin and yang role of pentraxins in immunity and inflammation is timely and significant as it may pave the way to achieve better clinical exploitation against various diseases.",,"['Magrini, Elena', 'Mantovani, Alberto', 'Garlanda, Cecilia']",,,,
,PMC,Assessment of the risk posed to Singapore by the 2015 Middle East respiratory syndrome outbreak in the Republic of Korea,http://dx.doi.org/10.5365/WPSAR.2015.6.4.008,PMC4957609,,,"OBJECTIVE: To assess the public health risk to Singapore posed by the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea in 2015. METHODS: The likelihood of importation of MERS cases and the magnitude of the public health impact in Singapore were assessed to determine overall risk. Literature on the epidemiology and contextual factors associated with MERS coronavirus infection was collected and reviewed. Connectivity between the Republic of Korea and Singapore was analysed. Public health measures implemented by the two countries were reviewed. RESULTS: The epidemiology of the 2015 MERS outbreak in the Republic of Korea remained similar to the MERS outbreaks in Saudi Arabia. In addition, strong infection control and response measures were effective in controlling the outbreak. In view of the air traffic between Singapore and MERS-affected areas, importation of MERS cases into Singapore is possible. Nonetheless, the risk of a serious public health impact to Singapore in the event of an imported case of MERS would be mitigated by its strong health-care system and established infection control practices. DISCUSSION: The MERS outbreak was sparked by an exported case from the Middle East, which remains a concern as the reservoir of infection (thought to be camels) continues to exist in the Middle East, and sporadic cases in the community and outbreaks in health-care settings continue to occur there. This risk assessment highlights the need for Singapore to stay vigilant and to continue enhancing core public health capacities to detect and respond to MERS coronavirus.",,"['Zhang, Emma Xuxiao', 'Oh, Olivia Seen Huey', 'See, Wanhan', 'Raj, Pream', 'James, Lyn', 'Khan, Kamran', 'Tey, Jeannie Su Hui']",,,,
,PMC,A novel glycogen synthase kinase-3 inhibitor optimized for acute myeloid leukemia differentiation activity,http://dx.doi.org/10.1158/1535-7163.MCT-15-0566,PMC4936967,,,"Standard therapies used for the treatment of Acute Myeloid Leukemia (AML) are cytotoxic agents that target rapidly proliferating cells. Unfortunately, this therapeutic approach has limited efficacy and significant toxicity and the majority of AML patients still die of their disease. In contrast to the poor prognosis of most AML patients, most individuals with a rare subtype of AML, Acute Promyelocytic Leukemia (APL), can be cured by differentiation therapy using regimens containing all-trans retinoic acid. GSK3 has previously been identified as a therapeutic target in AML where its inhibition can lead to the differentiation and growth arrest of leukemic cells. Unfortunately, existing GSK3 inhibitors lead to suboptimal differentiation activity making them less useful as clinical AML differentiation agents. Here we describe the discovery of a novel GSK3 inhibitor, GS87. GS87 was discovered in efforts to optimize GSK3 inhibition for AML differentiation activity. Despite GS87's dramatic ability to induce AML differentiation, kinase profiling reveals its high specificity in targeting GSK3 as compared to other kinases. GS87 demonstrates high efficacy in a mouse AML model system and unlike current AML therapeutics, exhibits little effect on normal bone marrow cells. GS87 induces potent differentiation by more effectively activating GSK3-dependent signaling components including MAPK signaling as compared to other GSK3 inhibitors. GS87 is a novel GSK3 inhibitor with therapeutic potential as a differentiation agent for non-promyelocytic AML.",,"['Hu, Sophia', 'Ueda, Masumi', 'Stetson, Lindsay', 'Ignatz-Hoover, James', 'Moreton, Stephen', 'Chakrabarti, Amit', 'Xia, Zhiqiang', 'Karan, Goutam', 'de Lima, Marcos', 'Agrawal, Mukesh K', 'Wald, David N']",,,,
,PMC,"Staphylococcus aureus Community-acquired Pneumonia: Prevalence, Clinical Characteristics, and Outcomes",http://dx.doi.org/10.1093/cid/ciw300,PMC4946021,,,"Background. Prevalence of Staphylococcus aureus community-acquired pneumonia (CAP) and its clinical features remain incompletely understood, complicating empirical selection of antibiotics. Methods. Using a multicenter, prospective surveillance study of adults hospitalized with CAP, we calculated the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) among all CAP episodes. We compared the epidemiologic, radiographic, and clinical characteristics of S. aureus CAP (per respiratory or blood culture) with those of pneumococcal (per respiratory or blood culture or urine antigen) and all-cause non-S. aureus CAP using descriptive statistics. Results. Among 2259 adults hospitalized for CAP, 37 (1.6%) had S. aureus identified, including 15 (0.7%) with MRSA and 22 (1.0%) with MSSA; 115 (5.1%) had Streptococcus pneumoniae. Vancomycin or linezolid was administered to 674 (29.8%) patients within the first 3 days of hospitalization. Chronic hemodialysis use was more common among patients with MRSA (20.0%) than pneumococcal (2.6%) and all-cause non-S. aureus (3.7%) CAP. Otherwise, clinical features at admission were similar, including concurrent influenza infection, hemoptysis, multilobar infiltrates, and prehospital antibiotics. Patients with MRSA CAP had more severe clinical outcomes than those with pneumococcal CAP, including intensive care unit admission (86.7% vs 34.8%) and in-patient mortality (13.3% vs 4.4%). Conclusions. Despite very low prevalence of S. aureus and, specifically, MRSA, nearly one-third of adults hospitalized with CAP received anti-MRSA antibiotics. The clinical presentation of MRSA CAP overlapped substantially with pneumococcal CAP, highlighting the challenge of accurately targeting empirical anti-MRSA antibiotics with currently available clinical tools and the need for new diagnostic strategies.",,"['Self, Wesley H.', 'Wunderink, Richard G.', 'Williams, Derek J.', 'Zhu, Yuwei', 'Anderson, Evan J.', 'Balk, Robert A.', 'Fakhran, Sherene S.', 'Chappell, James D.', 'Casimir, Geoffrey', 'Courtney, D. Mark', 'Trabue, Christopher', 'Waterer, Grant W.', 'Bramley, Anna', 'Magill, Shelley', 'Jain, Seema', 'Edwards, Kathryn M.', 'Grijalva, Carlos G.']",,,,
,PMC,Estimates of the risk of large or long-lasting outbreaks of Middle East respiratory syndrome after importations outside the Arabian Peninsula,http://dx.doi.org/10.1016/j.epidem.2016.04.002,PMC5047297,,,"We quantify outbreak risk after importations of Middle East respiratory syndrome outside the Arabian Peninsula. Data from 31 importation events show strong statistical support for lower transmissibility after early transmission generations. Our model projects the risk of ≥10, 100, and 500 transmissions as 11%, 2%, and 0.02%, and ≥1, 2, 3, and 4 generations as 23%, 14%, 0.9%, and 0.05%, respectively. Our results suggest tempered risk of large, long-lasting outbreaks with appropriate control measures.",,"['Toth, Damon J.A.', 'Tanner, Windy D.', 'Khader, Karim', 'Gundlapalli, Adi V.']",,,,
,PMC,Vaccine Technologies: From Whole Organisms to Rationally Designed Protein Assemblies,http://dx.doi.org/10.1016/j.bcp.2016.05.001,PMC5079805,,,"Vaccines have been the single most significant advancement in public health, preventing morbidity and mortality in millions of people annually. Vaccine development has traditionally focused on whole organism vaccines, either live attenuated or inactivated vaccines. While successful for many different infectious diseases whole organisms are expensive to produce, require culture of the infectious agent, and have the potential to cause vaccine associated disease in hosts. With advancing technology and a desire to develop safe, cost effective vaccine candidates, the field began to focus on the development of recombinantly expressed antigens known as subunit vaccines. While more tolerable, subunit vaccines tend to be less immunogenic. Attempts have been made to increase immunogenicity with the addition adjuvants, either immunostimulatory molecules or an antigen delivery system that increases immune responses to vaccines. An area of extreme interest has been the application of nanotechnology to vaccine development, which allows for antigens to be expressed on a particulate delivery system. One of the most exciting examples of nanovaccines are rationally designed protein nanoparticles. These nanoparticles use some of the basic tenants of structural biology, biophysical chemistry, and vaccinology to develop protective, safe, and easily manufactured vaccines. Rationally developed nanoparticle vaccines are one of the most promising candidates for the future of vaccine development.",,"['Karch, Christopher P.', 'Burkhard, Peter']",,,,
,PMC,Antibody treatment of Ebola and Sudan virus infection via a uniquely exposed epitope within the glycoprotein receptor-binding site,http://dx.doi.org/10.1016/j.celrep.2016.04.026,PMC4871745,,,"Previous efforts to identify cross-neutralizing antibodies to the receptor binding site (RBS) of ebolavirus glycoproteins have been unsuccessful, largely because the RBS is occluded on the viral surface. We report a monoclonal antibody (FVM04) that targets a uniquely exposed epitope within the RBS, cross-neutralizes Ebola (EBOV), Sudan (SUDV), and to a lesser extent Bundibugyo viruses, and shows protection against EBOV and SUDV in mice and guinea pigs. The antibody cocktail ZMapp™, is remarkably effective against EBOV (Zaire), but does not cross-neutralize other ebolaviruses. By replacing one of the ZMapp™ components with FVM04, we retained the anti-EBOV efficacy while extending the breadth of protection to SUDV, thereby generating a cross protective antibody cocktail. In addition, we report several mutations at the base of the ebolavirus glycoprotein that enhance the binding of FVM04 and other cross-reactive antibodies. These findings have important implications for pan-ebolavirus vaccine development and defining broadly protective antibody cocktails.",,"['Howell, Katie A.', 'Qiu, Xiangguo', 'Brannan, Jennifer M.', 'Bryan, Christopher', 'Davidson, Edgar', 'Holtsberg, Frederick W.', 'Wec, Anna Z.', 'Shulenin, Sergey', 'Biggins, Julia E.', 'Douglas, Robin', 'Enterlein, Sven G.', 'Turner, Hannah L.', 'Pallesen, Jesper', 'Murin, Charles D.', 'He, Shihua', 'Kroeker, Andrea', 'Vu, Hong', 'Herbert, Andrew S.', 'Fusco, Marnie L.', 'Nyakatura, Elisabeth K.', 'Lai, Jonathan R.', 'Keck, Zhen-Yong', 'Foung, Steven K. H.', 'Saphire, Erica Ollmann', 'Zeitlin, Larry', 'Ward, Andrew B.', 'Chandran, Kartik', 'Doranz, Benjamin J.', 'Kobinger, Gary P.', 'Dye, John M.', 'Aman, M. Javad']",,,,
,PMC,Trends and advances in food analysis by real-time polymerase chain reaction,http://dx.doi.org/10.1007/s13197-016-2205-0,PMC4921084,,,"Analyses to ensure food safety and quality are more relevant now because of rapid changes in the quantity, diversity and mobility of food. Food-contamination must be determined to maintain health and up-hold laws, as well as for ethical and cultural concerns. Real-time polymerase chain reaction (RT-PCR), a rapid and inexpensive quantitative method to detect the presence of targeted DNA-segments in samples, helps in determining both accidental and intentional adulterations of foods by biological contaminants. This review presents recent developments in theory, techniques, and applications of RT-PCR in food analyses, RT-PCR addresses the limitations of traditional food analyses in terms of sensitivity, range of analytes, multiplexing ability, cost, time, and point-of-care applications. A range of targets, including species of plants or animals which are used as food ingredients, food-borne bacteria or viruses, genetically modified organisms, and allergens, even in highly processed foods can be identified by RT-PCR, even at very low concentrations. Microfluidic RT-PCR eliminates the separate sample-processing step to create opportunities for point-of-care analyses. We also cover the challenges related to using RT-PCR for food analyses, such as the need to further improve sample handling. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13197-016-2205-0) contains supplementary material, which is available to authorized users.",,"['Salihah, Nur Thaqifah', 'Hossain, Mohammad Mosharraf', 'Lubis, Hamadah', 'Ahmed, Minhaz Uddin']",,,,
,PMC,20(th) International BioInformatics Workshop on Virus Evolution and Molecular Epidemiology,http://dx.doi.org/10.1093/ve/vev024,PMC6007559,,CC BY-NC,,2016 May 5,,Virus Evol,,,
,PMC,"Diversity and Evolutionary Histories of Human Coronaviruses NL63 and 229E Associated with Acute Upper Respiratory Tract Symptoms in Kuala Lumpur, Malaysia",http://dx.doi.org/10.4269/ajtmh.15-0810,PMC4856603,,,"The human alphacoronaviruses HCoV-NL63 and HCoV-229E are commonly associated with upper respiratory tract infections (URTI). Information on their molecular epidemiology and evolutionary dynamics in the tropical region of southeast Asia however is limited. Here, we analyzed the phylogenetic, temporal distribution, population history, and clinical manifestations among patients infected with HCoV-NL63 and HCoV-229E. Nasopharyngeal swabs were collected from 2,060 consenting adults presented with acute URTI symptoms in Kuala Lumpur, Malaysia, between 2012 and 2013. The presence of HCoV-NL63 and HCoV-229E was detected using multiplex polymerase chain reaction (PCR). The spike glycoprotein, nucleocapsid, and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. A total of 68/2,060 (3.3%) subjects were positive for human alphacoronavirus; HCoV-NL63 and HCoV-229E were detected in 45 (2.2%) and 23 (1.1%) patients, respectively. A peak in the number of HCoV-NL63 infections was recorded between June and October 2012. Phylogenetic inference revealed that 62.8% of HCoV-NL63 infections belonged to genotype B, 37.2% was genotype C, while all HCoV-229E sequences were clustered within group 4. Molecular dating analysis indicated that the origin of HCoV-NL63 was dated to 1921, before it diverged into genotype A (1975), genotype B (1996), and genotype C (2003). The root of the HCoV-229E tree was dated to 1955, before it diverged into groups 1–4 between the 1970s and 1990s. The study described the seasonality, molecular diversity, and evolutionary dynamics of human alphacoronavirus infections in a tropical region.",,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",,,,
,PMC,Enhanced detection of respiratory pathogens with nanotrap particles,http://dx.doi.org/10.1080/21505594.2016.1185585,PMC5029303,,,"The Influenza virus is a leading cause of respiratory disease in the United States each year. While the virus normally causes mild to moderate disease, hospitalization and death can occur in many cases. There are several methodologies that are used for detection; however problems such as decreased sensitivity and high rates of false-negative results may arise. There is a crucial need for an effective sample preparation technology that concentrates viruses at low abundance while excluding resident analytes that may interfere with detection. Nanotrap particles are hydrogel particles that are coupled to chemical dye affinity baits that bind a broad range of proteins and virions. Within minutes (<30 minutes), Nanotrap particles concentrate low abundant proteins and viruses from clinically complex matrices. Nanotrap particles with reactive red baits concentrated numerous respiratory viruses including various strains and subtypes of Influenza virus, Coronavirus, and Respiratory Syncytial Virus from saliva, nasal fluid swab specimens, and nasal aspirates. Detection was enhanced more than 10-fold when coupled to plaque assays and qRT-PCR. Importantly, Nanotrap particle can efficiently capture and concentrate multiple viral pathogens during a coinfection scenario. These results collectively demonstrate that Nanotrap particles are an important tool that can easily be integrated into various detection methodologies.",,"['Shafagati, Nazly', 'Fite, Katherine', 'Patanarut, Alexis', 'Baer, Alan', 'Pinkham, Chelsea', 'An, Soyeon', 'Foote, Benjamin', 'Lepene, Benjamin', 'Kehn-Hall, Kylene']",,,,
,PMC,Human Metapneumovirus Infections Following Hematopoietic Cell Transplantation: Factors Associated With Disease Progression,http://dx.doi.org/10.1093/cid/ciw284,PMC4928387,,,"Background. Human metapneumovirus (HMPV) is a newly identified pulmonary pathogen that can cause fatal lower respiratory tract disease (LRD) in hematopoietic cell transplantation (HCT) recipients. Little is known about progression rates from upper respiratory tract infection (URI) to LRD and risk factors associated with progression. Methods. A total of 118 HCT recipients receiving transplantation between 2004 and 2014 who had HMPV detected in nasopharyngeal, bronchoalveolar lavage, or lung biopsy samples by real-time reverse transcription polymerase chain reaction were retrospectively analyzed. Results. More than 90% of the cases were identified between December and May. Among the 118 HCT patients, 88 and 30 had URI alone and LRD, respectively. Among 30 patients with LRD, 17 patients progressed from URI to LRD after a median of 7 days (range, 2–63 days). The probability of progression to LRD within 40 days after URI was 16%. In Cox regression analysis, steroid use ≥1 mg/kg prior to URI diagnosis (hazard ratio [HR], 5.10; P = .004), low lymphocyte count (HR, 3.43; P = .011), and early onset of HMPV infection after HCT (before day 30 after HCT; HR, 3.54; P = .013) were associated with higher progression to LRD. The median viral load in nasal wash samples was 1.1 × 10(6) copies/mL (range, 3.3 × 10(2)–1.7 × 10(9)) with no correlation between the viral load and progression. Conclusions. Progression from URI to LRD occurred in up to 60% of HCT recipients with risk factors such as systemic corticosteroid use or low lymphocyte counts. Further studies are needed to define the role of viral load in the pathogenesis of progressive disease.",,"['Seo, Sachiko', 'Gooley, Ted A.', 'Kuypers, Jane M.', 'Stednick, Zachary', 'Jerome, Keith R.', 'Englund, Janet A.', 'Boeckh, Michael']",,,,
,PMC,Kinetics of Inactivation of Bacillus subtilis subsp. niger Spores and Staphylococcus albus on Paper by Chlorine Dioxide Gas in an Enclosed Space,http://dx.doi.org/10.1128/AEM.03940-15,PMC4959078,,,"Bacillus subtilis subsp. niger spore and Staphylococcus albus are typical biological indicators for the inactivation of airborne pathogens. The present study characterized and compared the behaviors of B. subtilis subsp. niger spores and S. albus in regard to inactivation by chlorine dioxide (ClO(2)) gas under different gas concentrations and relative humidity (RH) conditions. The inactivation kinetics under different ClO(2) gas concentrations (1 to 5 mg/liter) were determined by first-order and Weibull models. A new model (the Weibull-H model) was established to reveal the inactivation tendency and kinetics for ClO(2) gas under different RH conditions (30 to 90%). The results showed that both the gas concentration and RH were significantly (P < 0.05) and positively correlated with the inactivation of the two chosen indicators. There was a rapid improvement in the inactivation efficiency under high RH (>70%). Compared with the first-order model, the Weibull and Weibull-H models demonstrated a better fit for the experimental data, indicating nonlinear inactivation behaviors of the vegetative bacteria and spores following exposure to ClO(2) gas. The times to achieve a six-log reduction of B. subtilis subsp. niger spore and S. albus were calculated based on the established models. Clarifying the kinetics of inactivation of B. subtilis subsp. niger spores and S. albus by ClO(2) gas will allow the development of ClO(2) gas treatments that provide an effective disinfection method. IMPORTANCE Chlorine dioxide (ClO(2)) gas is a novel and effective fumigation agent with strong oxidization ability and a broad biocidal spectrum. The antimicrobial efficacy of ClO(2) gas has been evaluated in many previous studies. However, there are presently no published models that can be used to describe the kinetics of inactivation of airborne pathogens by ClO(2) gas under different gas concentrations and RH conditions. The first-order and Weibull (Weibull-H) models established in this study can characterize and compare the behaviors of Bacillus subtilis subsp. niger spores and Staphylococcus albus in regard to inactivation by ClO(2) gas, determine the kinetics of inactivation of two chosen strains under different conditions of gas concentration and RH, and provide the calculated time to achieve a six-log reduction. These results will be useful to determine effective conditions for ClO(2) gas to inactivate airborne pathogens in contaminated air and other environments and thus prevent outbreaks of airborne illness.",,"['Wang, Tao', 'Wu, Jinhui', 'Qi, Jiancheng', 'Hao, Limei', 'Yi, Ying', 'Zhang, Zongxing']",,,,
,PMC,Current Tools for Norovirus Drug Discovery,http://dx.doi.org/10.1080/17460441.2016.1178231,PMC4931794,,,"INTRODUCTION: Rapid transmission of norovirus often occurs due to its low infectious dosage, high genetic diversity and its short incubation time. The viruses cause acute gastroenteritis and may lead to death. Presently, no effective vaccine or selective drugs accepted by the United States Food and Drug Administration (FDA) are available for the treatment of norovirus. Advances in the development of norovirus replicon cell lines, GII.4-Sydney HuNoV strain human B cells, and murine and gnotobiotic pig norovirus models have facilitated the discovery of effective small molecule inhibitors in vitro and in vivo. AREAS COVERED: This review gives a brief discussion of the biology and replication of norovirus before highlighting the discovery of anti-norovirus molecules. The article coverage includes: an overview of the current state of norovirus drug discovery, the targeting of the norovirus life cycle, the inhibition of structural and nonstructural proteins of norovirus such as proteases and polymerase, and the blockage of virus entry into host cells. Finally, anti-norovirus drugs in the clinical development stage are described. EXPERT OPINION: The current approach for the counteraction of norovirus focuses on the inhibition of viral RNA polymerase, norovirus 3C-like protease and the structural proteins VP1 as well as the blockade of norovirus entry. Broad-spectrum anti-norovirus molecules, based on the inhibition of 3C-like protease, have been developed. Other host factors and ways to overcome the development of resistance through mutation are also being examined. A dual approach in targeting viral and host factors may lead to an effective counteraction of norovirus infection. Current successes in developing norovirus replicon harboring cells and norovirus infected human cells, as well as murine norovirus models and other animal models such as piglets have facilitated the discovery of effective drugs and helped our understanding of its mechanism of action.",,"['Weerasekara, Sahani', 'Prior, Allan M.', 'Hua, Duy H.']",,,,
,PMC,Comparing Single Case Design Overlap-Based Effect Size Metrics From Studies Examining Speech Generating Device Interventions,http://dx.doi.org/10.1352/1944-7558-121.3.169,PMC5313391,,,"Meaningfully synthesizing single case experimental data from intervention studies comprised of individuals with low incidence conditions and generating effect size estimates remains challenging. Seven effect size metrics were compared for single case design (SCD) data focused on teaching speech generating device use to individuals with intellectual and developmental disabilities (IDD) with moderate to profound levels of impairment. The effect size metrics included percent of data points exceeding the median (PEM), percent of nonoverlapping data (PND), improvement rate difference (IRD), percent of all nonoverlapping data (PAND), Phi, nonoverlap of all pairs (NAP), and Tau(novlap). Results showed that among the seven effect size metrics, PAND, Phi, IRD, and PND were more effective in quantifying intervention effects for the data sample (N = 285 phase or condition contrasts). Results are discussed with respect to issues concerning extracting and calculating effect sizes, visual analysis, and SCD intervention research in IDD.",,"['Chen, Mo', 'Hyppa-Martin, Jolene K.', 'Reichle, Joe E.', 'Symons, Frank J.']",,,,
,PMC,"Surfactant Lipids at the Host–Environment Interface. Metabolic Sensors, Suppressors, and Effectors of Inflammatory Lung Disease",http://dx.doi.org/10.1165/rcmb.2016-0011PS,PMC4942198,,,"The lipid composition of pulmonary surfactant is unlike that of any other body fluid. This extracellular lipid reservoir is also uniquely susceptible by virtue of its direct and continuous exposure to environmental oxidants, inflammatory agents, and pathogens. Historically, the greatest attention has been focused on those biophysical features of surfactant that serve to reduce surface tension at the air–liquid interface. More recently, surfactant lipids have also been recognized as bioactive molecules that maintain immune quiescence in the lung but can also be remodeled by the inhaled environment into neolipids that mediate key roles in inflammation, immunity, and fibrosis. This review focuses on the roles in inflammatory and infectious lung disease of two classes of native surfactant lipids, glycerophospholipids and sterols, and their corresponding oxidized species, oxidized glycerophospholipids and oxysterols. We highlight evidence that surfactant composition is sensitive to circulating lipoproteins and that the lipid milieu of the alveolus should thus be recognized as susceptible to diet and common systemic metabolic disorders. We also discuss intriguing evidence suggesting that oxidized surfactant lipids may represent an evolutionary link between immunity and tissue homeostasis that arose in the primordial lung. Taken together, the emerging picture is one in which the unique environmental susceptibility of the lung, together with its unique extracellular lipid requirements, may have made this organ both an evolutionary hub and an engine for lipid-immune cross-talk.",,"['Fessler, Michael B.', 'Summer, Ross S.']",,,,
,PMC,Serum antibody responses to vaccinal antigens in lean and obese geriatric dogs,,PMC4827746,,,"The immune responses in control dogs [1 to 4 years of age, body condition score (BCS): 4 to 5 out of 9] were compared to those of aging dogs (based on breed and body size) either categorized as lean (BCS: 4 to 5 out of 9) or obese (BCS: 8 to 9 out of 9). Of interest were the serum titers to the following common agents found in vaccines, canine parainfluenza virus (CPIV), canine parvovirus (CPV), canine distemper virus (CDV), canine respiratory coronavirus (CRCoV), and Bordetella bronchiseptica. There were no statistical differences in the antibodies to CPIV, B. bronchispetica, and CRCoV, among the age/weight categories, nor among the age/weight categories and the time, in days, between the date of sample collection and the date of the last recorded vaccination for CPIV, B. bronchiseptica, CPV, and CDV. For CPV, the control dogs had significantly (P < 0.002) higher serum neutralization (SN) titers than the lean geriatric dogs and the obese geriatric dogs. For CDV SN titers, the only statistically significant (P = 0.01) difference was that the control dogs had higher SN titers than the lean geriatric dogs.",,"['Ellis, John', 'Gow, Sheryl', 'Rhodes, Carrie', 'Lacoste, Stacey', 'Kong, Lyndsay', 'Musil, Kristyna', 'Snead, Elisabeth']",,,,
,PMC,Fatal extraintestinal toxoplasmosis in a young male cat with enlarged mesenteric lymph nodes,,PMC4827736,,,"A 22-month-old indoor/outdoor neutered male domestic short-haired cat had a history of progressive lethargy, vomiting, and decreased appetite. Abdominal ultrasound revealed an irregular hyperechoic mass in the mid-abdomen. He was unresponsive to symptomatic medical management and was euthanized after 3 days of hospitalization. A diagnosis of disseminated extraintestinal toxoplasmosis was made based on the finding of intracytoplasmic protozoan parasites on histopathological examination of mesenteric lymph nodes, hepatic and intestinal samples, and on immunohistochemistry.",,"['Cohen, Tamara M.', 'Blois, Shauna', 'Vince, Andrew R.']",,,,
,PMC,Public Health Surveillance: At the Core of the Global Health Security Agenda,http://dx.doi.org/10.1089/hs.2016.0002,PMC6937158,,,"Global health security involves developing the infrastructure and capacity to protect the health of people and societies worldwide. The acceleration of global travel and trade poses greater opportunities for infectious diseases to emerge and spread. The International Health Regulations (IHR) were adopted in 2005 with the intent of proactively developing public health systems that could react to the spread of infectious disease and provide better containment. Various challenges delayed adherence to the IHR. The Global Health Security Agenda came about as an international collaborative effort, working multilaterally among governments and across sectors, seeking to implement the IHR and develop the capacities to prevent, detect, and respond to public health emergencies of international concern. When examining the recent West African Ebola epidemic as a case study for global health security, both strengths and weaknesses in the public health response are evident. The central role of public health surveillance is a lesson reiterated by Ebola. Through further implementation of the Global Health Security Agenda, identified gaps in surveillance can be filled and global health security strengthened.",,"['Wolicki, Sara Beth', 'Nuzzo, Jennifer B.', 'Blazes, David L.', 'Pitts, Dana L.', 'Iskander, John K.', 'Tappero, Jordan W.']",,,,
,PMC,Laparotomic Approach for Collecting Serial Hepatic Biopsies in Rats (Rattus norvegicus) and Mice (Mus musculus),,PMC4865696,,,"Researchers often consult with laboratory animal veterinarians for suggestions on how to improve their protocols. We assisted a researcher in performing serial liver biopsies in rats (Rattus norvegicus) to assess the transport of iron on a cellular level. We developed a novel collection approach that used laparotomy through a midline abdominal incision and disposable biopsy punches to obtain liver samples at 3 different times at various intervals. We hypothesized the survival of the subjects undergoing the multiple survival procedures would be independent of the weight loss or gain sustained throughout the study. Although 2 rats died during the study, the results were statistically significant with regard to survival when comparing the Belgrade rats to the Sprague Dawley rats and Swiss Webster mice and were independent of the weight loss or gain incurred during the study. We also performed a pilot study in mice (Mus musculus), using the same method as in the rats, with equivalent results. Our study showed the survival of rodents that underwent multiple laparotomies and liver biopsies was independent of the weight gain or loss throughout the study.",,"['Garofalo, Jennifer-Marie', 'Black, Sasha P', 'Martin, Lisa B']",,,,
,PMC,"Postoperative Analgesia Due to Sustained-Release Buprenorphine, Sustained-Release Meloxicam, and Carprofen Gel in a Model of Incisional Pain in Rats (Rattus norvegicus)",,PMC4865691,,,"Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day–1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity–but not thermal hypersensitivity–on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR—but not Melox-SR or CG—effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.",,"['Seymour, Travis L', 'Adams, Sean C', 'Felt, Stephen A', 'Jampachaisri, Katechan', 'Yeomans, David C', 'Pacharinsak, Cholawat']",,,,
,PMC,Knowledge and Apprehension of Dental Patients about MERS-A Questionnaire Survey,http://dx.doi.org/10.7860/JCDR/2016/17519.7790,PMC4948537,,,"INTRODUCTION: Middle East Respiratory Syndrome (MERS) is a disease caused by beta corona virus. From April 11(th) to 9(th) June 2014, World Health Organization (WHO) reported a total of 402 laboratory confirmed cases of MERS from KSA, out of which 132 cases were reported from Riyadh alone. AIM: The aim of this study was to assess the knowledge and apprehension of patients about MERS visiting Al Farabi College of Dentistry, Riyadh, Saudi Arabia. MATERIALS AND METHODS: A cross-sectional questionnaire based survey was conducted which consisted of 10 self-prepared questions. A total of 404 patients participated in this study. RESULTS: Three hundred and forty patients had heard about MERS. Nearly a quarter of the patients (25.74%) were apprehensive about undergoing dental treatment because of MERS. A little more than half of the patients (50.99%) knew that camel was a source of Middle East Respiratory Syndrome-Corona virus. Most of the patients (80.72%) were aware of the infection control measures to be followed by dentist and 138 patients claimed they took some precaution when present inside the dental college. CONCLUSION: Majority of the patients had heard about MERS and was aware of the infection control measures. However, some patients were apprehensive about undergoing dental treatment because of MERS. Further steps need to be taken to educate the patient’s about transmission of MERS and infection control measures in a dental hospital.",,"['Ashok, Nipun', 'Rodrigues, Jean Clare', 'Azouni, Khalid', 'Darwish, Shorouk', 'Abuderman, Abdulwahab', 'Alkaabba, Abdul Aziz Fahad', 'Tarakji, Bassel']",,,,
,PMC,Characterization of Nipah virus infection in a model of human airway epithelial cells cultured at an air–liquid interface,http://dx.doi.org/10.1099/jgv.0.000441,PMC4851258,,,"Nipah virus (NiV) is an emerging paramyxovirus that can cause lethal respiratory illness in humans. No vaccine/therapeutic is currently licensed for humans. Human-to-human transmission was previously reported during outbreaks and NiV could be isolated from respiratory secretions, but the proportion of cases in Malaysia exhibiting respiratory symptoms was significantly lower than that in Bangladesh. Previously, we showed that primary human basal respiratory epithelial cells are susceptible to both NiV-Malaysia (M) and -Bangladesh (B) strains causing robust pro-inflammatory responses. However, the cells of the human respiratory epithelium that NiV targets are unknown and their role in NiV transmission and NiV-related lung pathogenesis is still poorly understood. Here, we characterized NiV infection of the human respiratory epithelium using a model of the human tracheal/bronchial (B-ALI) and small airway (S-ALI) epithelium cultured at an air–liquid interface. We show that NiV-M and NiV-B infect ciliated and secretory cells in B/S-ALI, and that infection of S-ALI, but not B-ALI, results in disruption of the epithelium integrity and host responses recruiting human immune cells. Interestingly, NiV-B replicated more efficiently in B-ALI than did NiV-M. These results suggest that the human tracheal/bronchial epithelium is favourable to NiV replication and shedding, while inducing a limited host response. Our data suggest that the small airways epithelium is prone to inflammation and lesions as well as constituting a point of virus entry into the pulmonary vasculature. The use of relevant models of the human respiratory tract, such as B/S-ALI, is critical for understanding NiV-related lung pathogenesis and identifying the underlying mechanisms allowing human-to-human transmission.",,"['Escaffre, Olivier', 'Borisevich, Viktoriya', 'Vergara, Leoncio A.', 'Wen, Julie W.', 'Long, Dan', 'Rockx, Barry']",,,,
,PMC,Severe adenovirus community-acquired pneumonia in immunocompetent adults: chest radiographic and CT findings,http://dx.doi.org/10.21037/jtd.2016.03.38,PMC4842832,,,"BACKGROUND: Severe adenovirus pneumonia and its associated imaging features are well-described in immunocompromised patients but are rare and poorly understood in immunocompetent adults. We sought to describe the radiographic and CT findings of severe adenovirus community-acquired pneumonia (CAP) in eight immunocompetent adults. METHODS: We reviewed systematically chest imaging manifestations of laboratory-confirmed severe adenovirus pneumonia in eight immunocompetent adults from April 2012 to April 2014. RESULTS: All patients showed abnormal results on initial chest radiograph and CT, with the exception of one normal initial chest radiograph. The abnormalities of the initial chest radiographs were unilateral (n=4) or bilateral (n=3), including consolidation (n=4), dense patchy opacity (n=3), ground glass opacity (GGO) (n=1), and pleural effusion (n=1). The initial CT findings consisted of unilateral (n=5) and bilateral (n=3) abnormalities, including consolidation (n=8), GGO (n=2), pleural effusion (n=3) and small nodules (n=1). Focal consolidation was the predominant finding in six patients whose initial CT scans were examined within one week after illness onset. Follow-up radiologic findings showed rapid development of bilateral consolidation within ten days after illness onset, usually accompanied by adjacent ground-glass opacity and pleural effusion. The parenchymal abnormalities began to absorb around two weeks after illness onset, with no appearances of fibrosis. CONCLUSIONS: Severe adenovirus CAP in immunocompetent adults mainly appears as focal consolidation followed by rapid progression to bilateral consolidation, usually accompanied by adjacent GGO and pleural effusion, which may resemble bacterial pneumonia. Adenovirus should be considered in severe pneumonia cases with negative cultures and failure to respond to antibiotics.",,"['Tan, Dingyu', 'Fu, Yangyang', 'Xu, Jun', 'Wang, Zhiwei', 'Cao, Jian', 'Walline, Joseph', 'Zhu, Huadong', 'Yu, Xuezhong']",,,,
,PMC,Prevalence of neutralizing antibodies to common respiratory viruses in intravenous immunoglobulin and in healthy donors in southern China,http://dx.doi.org/10.21037/jtd.2016.03.29,PMC4842828,,,"BACKGROUND: Acute respiratory infections (ARIs) are a leading cause of death among children under the age of 5. However, there are no effective drugs for most of these severe viral infections. Passive immunotherapy with convalescent plasma or hyperimmune intravenous immunoglobulin (H-IVIG) is a potential therapeutic option for serious viral infections. It is important to find a suitable source of convalescent plasma and of H-IVIG containing high titer neutralizing antibodies (NAbs). METHODS: Sera from 96 healthy adult donors in southern China and commercially available IVIG were analyzed for the titers of NAb to several most common respiratory viruses including respiratory syncytial virus (RSV), seasonal influenza A (InfA), enterovirus 71 (EV71), coxsackievirus A16 (CA16), adenovirus type 3 (Ad3) and a recent epidemic adenovirus type 55 (Ad55) by microneutralization test. RESULTS: A high proportion of samples from healthy adult donors were positive for NAbs (>16) to all the viruses except Ad55. A different proportion of these samples had high NAb titers (>512) for InfA (25%), Ad3 (17.71%), RSV (9.38%), EV71 (1.04%), CA16 (3.13%), and Ad55 (4.17%). Commercially available IVIG had high NAb titers to InfA and Ad3 (>1,000) and lower NAb titers to RSV [320], EV71 [160], and CA16 [160]. Strikingly, IVIG also had a high NAb titer to Ad55 (>1,000). CONCLUSIONS: Convalescent plasma could be screened from healthy blood volunteers to establish blood banks and to prepare specific H-IVIG for treating severe ARIs caused by common respiratory viruses.",,"['Tian, Xingui', 'Jiang, Zaixue', 'Ma, Qiang', 'Liu, Qian', 'Lu, Xiaomei', 'Liu, Wenkuan', 'Liao, Xiaohong', 'Zhou, Rong', 'Su, Xiaobo', 'Luo, Qingming']",,,,
,PMC,Human coronavirus and severe acute respiratory infection in Southern Brazil,http://dx.doi.org/10.1080/20477724.2016.1181294,PMC4984956,,,"Human coronaviruses (HCoVs) are an important cause of respiratory tract infection and are responsible for causing the common cold in the general population. Thus, adequate surveillance of HCoV is essential. This study aimed to analyze the impact of HCoV infections and their relation to severe acute respiratory infection (SARI) in a hospitalized population in Southern Brazil. A cross-sectional study was conducted at a tertiary care hospital, and assessed inpatients under investigation for SARI by the hospital epidemiology department, and all patients who had nasopharyngeal aspirates collected from January 2012 to December 2013 to detect respiratory viruses (RVs). Viral infection was detected by multiplex reverse transcriptase polymerase chain reaction (RT-PCR), with primers specific to the subtypes HCoV-229E/NL63 and OC43/HKU1. The overall positivity rate was 58.8% (444/755), and HCoVs were detected in 7.6% (n = 34) of positive samples. Children below two years of age were most frequently affected (62%). Comorbidities were more likely to be associated with HCoVs than with other RVs. Immunosuppression was an independent risk factor for HCoV infection (OR = 3.5, 95% CI 1.6–7.6). Dyspnea was less frequently associated with HCoV infection (p < 0.001), and HCoV accounted for 6% of the SARI cases. Three patients infected with HCoV (9%) died from respiratory infection. HCoVs are important respiratory pathogens, especially in hospitalized children under 2 years of age and in immunosuppressed patients. They may account for a small proportion of SARI diagnoses, increased need for mechanical ventilation, intensive care unit admission, and death.",,"['Trombetta, Hygor', 'Faggion, Heloisa Z.', 'Leotte, Jaqueline', 'Nogueira, Meri B.', 'Vidal, Luine R. R.', 'Raboni, Sonia M.']",,,,
,PMC,Determining Persistence of Bocavirus DNA in the Respiratory Tract of Children by Pyrosequencing,http://dx.doi.org/10.1097/INF.0000000000001058,PMC4829457,,,"BACKGROUND: Although human bocavirus type 1 (HBoV1) is a respiratory pathogen, presence of HBoV-DNA in secretions of asymptomatic children raised the question on the significance of HBoV-positive results. METHODS: Archived specimens from a prospective, longitudinal study were tested for HBoV. A total of 94 children (aged 6 – 36 m) were HBoV(+) during 172 upper respiratory tract infection (URI) and/ or acute otitis media (AOM) episodes. We used pyrosequencing of NP1, VP1 and VP2 genes to type HBoV and subtype HBoV1 in these specimens. RESULTS: Of the specimens tested, HBoV-DNA were successfully sequenced in 128 (74%) samples from 70 children; all were HBoV type 1. Subtypes identified (n=108) were: LWK/TW (63%), LWK/BJ (20%), Bonn/BJ (16%) and LWK/KU3 (1%). Of 46 children for whom shedding pattern could be determined, viral clearance within 30d (13-29d) occurred in 28%; another 22% of children had no recurrence after 32 to 267d. Prolonged virus presence of >30 d (34 to 181d+) occurred in 22%; intermittent detection (61+ to 170d+) in 20%. Infection with the same HBoV1 subtype after 4-5 negative samples (244 and 265d interval) occurred in 4%. Infection with 2 different HBoV1 subtypes (29 and 87d apart) occurred in only 4%. Newly acquired HBoV1-URI resulted in AOM in 53% of cases. CONCLUSIONS: Children with HBoV1 infection commonly shed for a prolonged period leading to repeated viral DNA detection. Recurrence after 8-9 m suggests possible persistence and reactivation. Infections with 2 different HBoV1 subtypes within one-year period are uncommon. Newly acquired HBoV1-URI is often complicated by AOM.",,"['Wagner, Johana Castro', 'Pyles, Richard B.', 'Miller, Aaron L.', 'Nokso-Koivisto, J.', 'Loeffelholz, Michael J.', 'Chonmaitree, Tasnee']",,,,
,PMC,"Social Media's Initial Reaction to Information and Misinformation on Ebola, August 2014: Facts and Rumors",,PMC4869079,,,"OBJECTIVE: We analyzed misinformation about Ebola circulating on Twitter and Sina Weibo, the leading Chinese microblog platform, at the outset of the global response to the 2014–2015 Ebola epidemic to help public health agencies develop their social media communication strategies. METHODS: We retrieved Twitter and Sina Weibo data created within 24 hours of the World Health Organization announcement of a Public Health Emergency of International Concern (Batch 1 from August 8, 2014, 06:50:00 Greenwich Mean Time [GMT] to August 9, 2014, 06:49:59 GMT) and seven days later (Batch 2 from August 15, 2014, 06:50:00 GMT to August 16, 2014, 06:49:59 GMT). We obtained and analyzed a 1% random sample of tweets containing the keyword Ebola. We retrieved all Sina Weibo posts with Chinese keywords for Ebola for analysis. We analyzed changes in frequencies of keywords, hashtags, and Web links using relative risk (RR) and c(2) feature selection algorithm. We identified misinformation by manual coding and categorizing randomly selected sub-datasets. RESULTS: We identified two speculative treatments (i.e., bathing in or drinking saltwater and ingestion of Nano Silver, an experimental drug) in our analysis of changes in frequencies of keywords and hashtags. Saltwater was speculated to be protective against Ebola in Batch 1 tweets but their mentions decreased in Batch 2 (RR=0.11 for “salt” and RR=0.14 for “water”). Nano Silver mentions were higher in Batch 2 than in Batch 1 (RR=10.5). In our manually coded samples, Ebola-related misinformation constituted about 2% of Twitter and Sina Weibo content. A range of 36%–58% of the posts were news about the Ebola outbreak and 19%–24% of the posts were health information and responses to misinformation in both batches. In Batch 2, 43% of Chinese microblogs focused on the Chinese government sending medical assistance to Guinea. CONCLUSION: Misinformation about Ebola was circulated at a very low level globally in social media in either batch. Qualitative and quantitative analyses of social media posts can provide relevant information to public health agencies during emergency responses.",,"['Fung, Isaac Chun-Hai', 'Fu, King-Wa', 'Chan, Chung-Hong', 'Chan, Benedict Shing Bun', 'Cheung, Chi-Ngai', 'Abraham, Thomas', 'Tse, Zion Tsz Ho']",,,,
,PMC,Porcine Reproductive and Respiratory Syndrome Virus Utilizes Nanotubes for Intercellular Spread,http://dx.doi.org/10.1128/JVI.00036-16,PMC4859731,,,"Intercellular nanotube connections have been identified as an alternative pathway for cellular spreading of certain viruses. In cells infected with porcine reproductive and respiratory syndrome virus (PRRSV), nanotubes were observed connecting two distant cells with contiguous membranes, with the core infectious viral machinery (viral RNA, certain replicases, and certain structural proteins) present in/on the intercellular nanotubes. Live-cell movies tracked the intercellular transport of a recombinant PRRSV that expressed green fluorescent protein (GFP)-tagged nsp2. In MARC-145 cells expressing PRRSV receptors, GFP-nsp2 moved from one cell to another through nanotubes in the presence of virus-neutralizing antibodies. Intercellular transport of viral proteins did not require the PRRSV receptor as it was observed in receptor-negative HEK-293T cells after transfection with an infectious clone of GFP-PRRSV. In addition, GFP-nsp2 was detected in HEK-293T cells cocultured with recombinant PRRSV-infected MARC-145 cells. The intercellular nanotubes contained filamentous actin (F-actin) with myosin-associated motor proteins. The F-actin and myosin IIA were identified as coprecipitates with PRRSV nsp1β, nsp2, nsp2TF, nsp4, nsp7-nsp8, GP5, and N proteins. Drugs inhibiting actin polymerization or myosin IIA activation prevented nanotube formation and viral clusters in virus-infected cells. These data lead us to propose that PRRSV utilizes the host cell cytoskeletal machinery inside nanotubes for efficient cell-to-cell spread. This form of virus transport represents an alternative pathway for virus spread, which is resistant to the host humoral immune response. IMPORTANCE Extracellular virus particles transmit infection between organisms, but within infected hosts intercellular infection can be spread by additional mechanisms. In this study, we describe an alternative pathway for intercellular transmission of PRRSV in which the virus uses nanotube connections to transport infectious viral RNA, certain replicases, and certain structural proteins to neighboring cells. This process involves interaction of viral proteins with cytoskeletal proteins that form the nanotube connections. Intercellular viral spread through nanotubes allows the virus to escape the neutralizing antibody response and may contribute to the pathogenesis of viral infections. The development of strategies that interfere with this process could be critical in preventing the spread of viral infection.",,"['Guo, Rui', 'Katz, Benjamin B.', 'Tomich, John M.', 'Gallagher, Tom', 'Fang, Ying']",,,,
,PMC,2C Proteins of Enteroviruses Suppress IKKβ Phosphorylation by Recruiting Protein Phosphatase 1,http://dx.doi.org/10.1128/JVI.03021-15,PMC4859720,,,"The NF-κB signaling network, which is an ancient signaling pathway, plays a pivotal role in innate immunity and constitutes a first line of defense against invading pathogens, including viruses. However, numerous viruses possess evolved strategies to antagonize the activation of the NF-κB signaling pathway. Our previous study demonstrated that the nonstructural protein 2C of enterovirus 71 (EV71), which is the major pathogen of hand, foot, and mouth disease, inhibits tumor necrosis factor alpha (TNF-α)-mediated activation of NF-κB by suppressing IκB kinase β (IKKβ) phosphorylation. Nevertheless, the mechanism underlying the inhibition of IKKβ phosphorylation by EV71 2C remains largely elusive. We demonstrate that EV71 2C interacts with all isoforms of the protein phosphatase 1 (PP1) catalytic subunit (the PP1α, PP1β, and PP1γ isoforms) through PP1-docking motifs. EV71 2C has no influence on the subcellular localization of PP1. In addition, the PP1-binding-deficient EV71 2C mutant 3E3L nearly completely lost the ability to suppress IKKβ phosphorylation and NF-κB activation was markedly restored in the mutant, thereby indicating that PP1 binding is efficient for EV71 2C-mediated inhibition of IKKβ phosphorylation and NF-κB activation. We further demonstrate that 2C forms a complex with PP1 and IKKβ to dephosphorylate IKKβ. Notably, we reveal that other human enteroviruses, including poliovirus (PV), coxsackie A virus 16 (CVA16), and coxsackie B virus 3 (CVB3), use 2C proteins to recruit PP1, leading to the inhibition of IKKβ phosphorylation. Our findings indicate that enteroviruses exploit a novel mechanism to inhibit IKKβ phosphorylation by recruiting PP1 and IKKβ to form a complex through 2C proteins, which ultimately results in the inhibition of the NF-κB signaling pathway. IMPORTANCE The innate antiviral immunity system performs an essential function in recognizing and eliminating invading viruses. Enteroviruses include a number of important human pathogens, including poliovirus (PV), EV71, and coxsackieviruses (CVs). As 2C is the most conserved and complex nonstructural protein of enteroviruses, its biological function is largely unclear, whereas the 2A and 3C proteinases of enteroviruses are well characterized. We reveal that EV71 2C forms a complex with PP1 and IKKβ to maintain IKKβ in an unphosphorylated and inactive state, resulting in the inactivation of the TNF-α-mediated NF-κB signaling pathway. We provide evidence that the 2C proteins of the enteroviruses PV, CVA16, and CVB3 suppress IKKβ phosphorylation through the same mechanism involving PP1. We demonstrate that enteroviruses exploit a novel mechanism involving PP1 to regulate innate antiviral immunity, and our findings may be particularly important for understanding the pathogenicity of enteroviruses.",,"['Li, Qian', 'Zheng, Zhenhua', 'Liu, Yan', 'Zhang, Zhenfeng', 'Liu, Qingshi', 'Meng, Jin', 'Ke, Xianliang', 'Hu, Qinxue', 'Wang, Hanzhong']",,,,
,PMC,Zika Virus: New Clinical Syndromes and Its Emergence in the Western Hemisphere,http://dx.doi.org/10.1128/JVI.00252-16,PMC4859708,,,"Zika virus (ZIKV) had remained a relatively obscure flavivirus until a recent series of outbreaks accompanied by unexpectedly severe clinical complications brought this virus into the spotlight as causing an infection of global public health concern. In this review, we discuss the history and epidemiology of ZIKV infection, recent outbreaks in Oceania and the emergence of ZIKV in the Western Hemisphere, newly ascribed complications of ZIKV infection, including Guillain-Barré syndrome and microcephaly, potential interactions between ZIKV and dengue virus, and the prospects for the development of antiviral agents and vaccines.",,"['Lazear, Helen M.', 'Diamond, Michael S.']",,,,
,PMC,Bat Hunting and Bat-Human Interactions in Bangladeshi Villages: Implications for Zoonotic Disease Transmission and Bat Conservation,http://dx.doi.org/10.1111/tbed.12505,PMC5086320,,,"Bats are an important reservoir for emerging zoonotic diseases. Close human-bat interactions, including the sharing of living spaces and hunting and butchering of bats for food and medicines, may lead to spillover of zoonotic disease into human populations. We used bat exposure and environmental data gathered from 207 Bangladeshi villages to characterize bat exposures and hunting in Bangladesh. Eleven percent of households reported having a bat roost near their homes, 65% reported seeing bats flying over their households at dusk, and 31% reported seeing bats inside their compounds or courtyard areas. Twenty percent of households reported that members had at least daily exposure to bats. Bat hunting occurred in 49% of the villages surveyed and was more likely to occur in households that reported nearby bat roosts (adjusted prevalence ratio [aPR] 2.3, 95% CI 1.1-4.9) and villages located in Northwest (aPR 7.5, 95% CI 2.5-23.0) and Southwest (aPR 6.8, 95% CI 2.1-21.6) regions. Our results suggest high exposure to bats and widespread hunting throughout Bangladesh. This has implications both for zoonotic disease spillover and bat conservation.",,"['Openshaw, John J', 'Hegde, Sonia', 'Sazzad, Hossain M S', 'Khan, Salah Uddin', 'Hossain, M Jahangir', 'Epstein, Jonathan H', 'Daszak, Peter', 'Gurley, Emily S', 'Luby, Stephen P']",,,,
,PMC,"Structure-Based Design and Synthesis of Triazole-based Macrocyclic Inhibitors of Norovirus Protease: Structural, Biochemical, Spectroscopic, and Antiviral Studies",http://dx.doi.org/10.1016/j.ejmech.2016.04.013,PMC4916972,,,"Outbreaks of acute gastroenteritis caused by noroviruses constitute a public health concern worldwide. To date, there are no approved drugs or vaccines for the management and prophylaxis of norovirus infections. A potentially effective strategy for the development of norovirus therapeutics entails the discovery of inhibitors of norovirus 3CL protease, an enzyme essential for noroviral replication. We describe herein the structure-based design of the first class of permeable, triazole-based macrocyclic inhibitors of norovirus 3C-like protease, as well as pertinent X-ray crystallographic, biochemical, spectroscopic, and antiviral studies.",,"['Weerawarna, Pathum M.', 'Kim, Yunjeong', 'Kankanamalage, Anushka C. Galasiti', 'Damalanka, Vishnu C.', 'Lushington, Gerald H.', 'Alliston, Kevin R.', 'Mehzabeen, Nurjahan', 'Battaile, Kevin P.', 'Lovell, Scott', 'Chang, Kyeong-Ok', 'Groutas, William C.']",,,,
,PMC,A Dual Protease Approach for Expression and Affinity Purification of Recombinant Proteins,http://dx.doi.org/10.1016/j.ab.2016.04.006,PMC4877217,,,"We describe a new method for affinity purification of recombinant proteins using a dual protease protocol. Escherichia coli maltose binding protein (MBP) is employed as an N-terminal tag to increase the yield and solubility of its fusion partners. The MBP moiety is then removed by rhinovirus 3C protease, prior to purification, to yield an N-terminally His(6)-tagged protein. Proteins that are only temporarily rendered soluble by fusing them to MBP are readily identified at this stage because they will precipitate after the MBP tag is removed by 3C protease. The remaining soluble His(6)-tagged protein, if any, is subsequently purified by immobilized metal affinity chromatography (IMAC). Finally, the N-terminal His(6) tag is removed by His(6)-tagged tobacco etch virus (TEV) protease to yield the native recombinant protein, and the His(6)-tagged contaminants are removed by adsorption during a second round of IMAC, leaving only the untagged recombinant protein in the column effluent. The generic strategy described here saves time and effort by removing insoluble aggregates at an early stage in the process while also reducing the tendency of MBP to “stick” to its fusion partners during affinity purification.",,"['Raran-Kurussi, Sreejith', 'Waugh, David S.']",,,,
,PMC,A key role for the carboxy-terminal tail of the murine coronavirus nucleocapsid protein in coordination of genome packaging,http://dx.doi.org/10.1016/j.virol.2016.04.009,PMC4884538,,,"The prototype coronavirus mouse hepatitis virus (MHV) exhibits highly selective packaging of its genomic positive-stranded RNA into assembled virions, despite the presence in infected cells of a large excess of subgenomic viral mRNAs. One component of this selectivity is the MHV packaging signal (PS), an RNA structure found only in genomic RNA and not in subgenomic RNAs. It was previously shown that a major determinant of PS recognition is the second of the two RNA-binding domains of the viral nucleocapsid (N) protein. We have now found that PS recognition additionally depends upon a segment of the carboxy-terminal tail (domain N3) of the N protein. Since domain N3 is also the region of N protein that interacts with the membrane (M) protein, this finding suggests a mechanism by which selective genome packaging is accomplished, through the coupling of genome encapsidation to virion assembly.",,"['Kuo, Lili', 'Koetzner, Cheri A.', 'Masters, Paul S.']",,,,
,PMC,BCX4430 – a broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease,http://dx.doi.org/10.1016/j.jiph.2016.04.002,PMC4937725,,,"The adenosine nucleoside analog BCX4430 is a direct-acting antiviral drug under investigation for the treatment of serious and life-threatening infections from highly pathogenic viruses, such as the Ebola virus. Cellular kinases phosphorylate BCX4430 to a triphosphate that mimics ATP; viral RNA polymerases incorporate the drug’s monophosphate nucleotide into the growing RNA chain, causing premature chain termination. BCX4430 is active in vitro against many RNA viral pathogens, including the filoviruses and emerging infectious agents such as MERS-CoV and SARS-CoV. In vivo, BCX4430 is active after intramuscular, intraperitoneal, and oral administration in a variety of experimental infections. In nonclinical studies involving lethal infections with Ebola virus, Marburg virus, Rift Valley fever virus, and Yellow Fever virus, BCX4430 has demonstrated pronounced efficacy. In experiments conducted in several models, both a reduction in the viral load and an improvement in survival were found to be related to the dose of BCX4430. A Phase 1 clinical trial of intramuscular administration of BCX4430 in healthy subjects is currently ongoing.",,"['Taylor, Raymond', 'Kotian, Pravin', 'Warren, Travis', 'Panchal, Rekha', 'Bavari, Sina', 'Julander, Justin', 'Dobo, Sylvia', 'Rose, Angela', 'El-Kattan, Yahya', 'Taubenheim, Brian', 'Babu, Yarlagadda', 'Sheridan, William P.']",,,,
,PMC,Role of the ACE2/Angiotensin 1–7 axis of the Renin-Angiotensin System in Heart Failure,http://dx.doi.org/10.1161/CIRCRESAHA.116.307708,PMC4939482,,,"Heart failure remains the most common cause of death and disability, and a major economic burden, in industrialized nations. Physiological, pharmacological, and clinical studies have demonstrated that activation of the renin-angiotensin system is a key mediator of heart failure progression. Angiotensin converting enzyme 2 (ACE2), a homologue of ACE, is a monocarboxypeptidase that converts angiotensin II (Ang II) into angiotensin 1–7 (Ang 1–7) which, by virtue of its actions on the Mas receptor, opposes the molecular and cellular effects of Ang II. ACE2 is widely expressed in cardiomyocytes, cardiofibroblasts, and coronary endothelial cells. Recent preclinical translational studies confirmed a critical counter-regulatory role of ACE2/Ang 1–7 axis on the activated renin-angiotensin system that results in heart failure with preserved ejection fraction. While loss of ACE2 enhances susceptibility to heart failure, increasing ACE2 level prevents and reverses the heart failure phenotype. ACE2 and Ang 1–7 have emerged as a key protective pathway against heart failure with reduced and preserved ejection fraction. Recombinant human ACE2 has been tested in phase I and II clinical trials without adverse effects while lowering and increasing plasma Ang II and Ang 1–7 levels, respectively. This review discusses the transcriptional and post-transcriptional regulation of ACE2 and the role of the ACE2/Ang 1–7 axis in cardiac physiology and in the pathophysiology of heart failure. The pharmacological and therapeutic potential of enhancing ACE2/Ang 1–7 action as a novel therapy for heart failure is highlighted.",,"['Patel, Vaibhav B.', 'Zhong, Jiu-Chang', 'Grant, Maria B.', 'Oudit, Gavin Y.']",,,,
,PMC,Analyses of Coronavirus Assembly Interactions with Interspecies Membrane and Nucleocapsid Protein Chimeras,http://dx.doi.org/10.1128/JVI.03212-15,PMC4836358,,,"The coronavirus membrane (M) protein is the central actor in virion morphogenesis. M organizes the components of the viral membrane, and interactions of M with itself and with the nucleocapsid (N) protein drive virus assembly and budding. In order to further define M-M and M-N interactions, we constructed mutants of the model coronavirus mouse hepatitis virus (MHV) in which all or part of the M protein was replaced by its phylogenetically divergent counterpart from severe acute respiratory syndrome coronavirus (SARS-CoV). We were able to obtain viable chimeras containing the entire SARS-CoV M protein as well as mutants with intramolecular substitutions that partitioned M protein at the boundaries between the ectodomain, transmembrane domains, or endodomain. Our results show that the carboxy-terminal domain of N protein, N3, is necessary and sufficient for interaction with M protein. However, despite some previous genetic and biochemical evidence that mapped interactions with N to the carboxy terminus of M, it was not possible to define a short linear region of M protein sufficient for assembly with N. Thus, interactions with N protein likely involve multiple linearly discontiguous regions of the M endodomain. The SARS-CoV M chimera exhibited a conditional growth defect that was partially suppressed by mutations in the envelope (E) protein. Moreover, virions of the M chimera were markedly deficient in spike (S) protein incorporation. These findings suggest that the interactions of M protein with both E and S protein are more complex than previously thought. IMPORTANCE The assembly of coronavirus virions entails concerted interactions among the viral structural proteins and the RNA genome. One strategy to study this process is through construction of interspecies chimeras that preserve or disrupt particular inter- or intramolecular associations. In this work, we replaced the membrane (M) protein of the model coronavirus mouse hepatitis virus with its counterpart from a heterologous coronavirus. The results clarify our understanding of the interaction between the coronavirus M protein and the nucleocapsid protein. At the same time, they reveal unanticipated complexities in the interactions of M with the viral spike and envelope proteins.",,"['Kuo, Lili', 'Hurst-Hess, Kelley R.', 'Koetzner, Cheri A.', 'Masters, Paul S.']",,,,
,PMC,Mapping Antigenic Epitopes on the Human Bocavirus Capsid,http://dx.doi.org/10.1128/JVI.02998-15,PMC4836351,,,"Human bocaviruses (HBoV1 to -4) are emerging pathogens associated with pneumonia and/or diarrhea in young children. Currently, there is no treatment or vaccination, so there is a need to study these pathogens to understand their disease mechanisms on a molecular and structural level for the development of control strategies. Here, we report the structures of six HBoV monoclonal antibody (MAb) fragment complexes, HBoV1-15C6, HBoV2-15C6, HBoV4-15C6, HBoV1-4C2, HBoV1-9G12, and HBoV1-12C1, determined by cryo-electron microscopy and three-dimensional image reconstruction to 18.0- to 8.5-Å resolution. Of these, the 15C6 MAb cross-reacted with HBoV1, HBoV2, and HBoV4, while the 4C2, 12C1, and 9G12 MAbs recognized only HBoV1. Pseudoatomic modeling mapped the 15C6 footprint to the capsid surface DE and HI loops, at the 5-fold axis and the depression surrounding it, respectively, which are conserved motifs in Parvoviridae. The footprints for 4C2, 12C1, and 9G12 span the surface loops that assemble portions of the 2-/5-fold wall (a raised surface feature between the 2-fold and 5-fold axes of symmetry) and the shoulder of the 3-fold protrusions. The MAb footprints, cross reactive and strain specific, coincide with regions with high and low sequence/structural identities, respectively, on the capsid surfaces of the HBoVs and identify potential regions for the development of peptide vaccines for these viruses. IMPORTANCE Human bocaviruses (HBoVs) may cause severe respiratory and gastrointestinal infections in young children. The nonenveloped parvovirus capsid carries determinants of host and tissue tropism, pathogenicity, genome packaging, assembly, and antigenicity important for virus infection. This information is currently unavailable for the HBoVs and other bocaparvoviruses. This study identifies three strain-specific antigenic epitopes on the HBoV1 capsid and a cross-reactive epitope on the HBoV1, HBoV2, and HBoV4 capsids using structures of capsid-antibody complexes determined using cryo-electron microscopy and image reconstruction. This is the first study to report the highly conserved parvovirus DE loop at the 5-fold axis as a determinant of antigenicity. Additionally, knowledge of the strain-specific and conserved antigenic epitopes of the bocaviruses can be instrumental in characterization of the virus life cycle, development of peptide vaccines, and generation of gene delivery vectors for cystic fibrosis given the strict tropism of HBoV1 for human airway epithelial cells.",,"['Kailasan, Shweta', 'Garrison, Jamie', 'Ilyas, Maria', 'Chipman, Paul', 'McKenna, Robert', 'Kantola, Kalle', 'Söderlund-Venermo, Maria', 'Kučinskaitė-Kodzė, Indrė', 'Žvirblienė, Aurelija', 'Agbandje-McKenna, Mavis']",,,,
,PMC,The Attenuation Phenotype of a Ribavirin-Resistant Porcine Reproductive and Respiratory Syndrome Virus Is Maintained during Sequential Passages in Pigs,http://dx.doi.org/10.1128/JVI.02836-15,PMC4836337,,,"In a previous study, ribavirin-resistant porcine reproductive and respiratory syndrome virus (PRRSV) mutants (RVRp13 and RVRp22) were selected, and their resistance against random mutation was shown in cultured cells. In the present study, these ribavirin-resistant mutants were evaluated in terms of their genetic and phenotypic stability during three pig-to-pig passages in comparison with modified live virus (MLV) (Ingelvac PRRS MLV). Pigs challenged with RVRp22 had significantly lower (P < 0.05) viral loads in sera and tissues than pigs challenged with MLV or RVRp13 at the first passage, and the attenuated replication of RVRp22 was maintained until the third passage. Viral loads in sera and tissues dramatically increased in pigs challenged with MLV or RVRp13 during the second passage. Consistently, all five sequences associated with the attenuation of virulent PRRSV in RVRp13 and MLV quickly reverted to wild-type sequences during the passages, but two attenuation sequences were maintained in RVRp22 even after the third passage. In addition, RVRp22 showed a significantly lower (P < 0.001) mutation frequency in nsp2, which is one of the most variable regions in the PRRSV genome, than MLV. Nine unique mutations were found in open reading frames (ORFs) 1a, 2, and 6 in the RVRp22 genome based on full-length sequence comparisons with RVRp13, VR2332 (the parental virus of RVRp13 and RVRp22), and MLV. Based on these results, it was concluded that RVRp22 showed attenuated replication in pigs; further, because of the high genetic stability of RVRp22, its attenuated phenotype was stable even after three sequential passages in pigs. IMPORTANCE PRRSV is a rapidly evolving RNA virus. MLV vaccines are widely used to control PRRS; however, there have been serious concerns regarding the use of MLV as a vaccine virus due to the rapid reversion to virulence during replication in pigs. As previously reported, ribavirin is an effective antiviral drug against many RNA viruses. Ribavirin-resistant mutants reemerged by escaping lethal mutagenesis when the treatment concentration was sublethal, and those mutants were genetically more stable than parental viruses. In a previous study, two ribavirin-resistant PRRSV mutants (RVRp13 and RVRp22) were selected, and their higher genetic stability was shown in vitro. Consequently, in the present study, both of the ribavirin-resistant mutants were evaluated in terms of their genetic and phenotypic stability in vivo. RVRp22 was found to exhibit higher genetic and phenotypic stability than MLV, and nine unique mutations were identified in the RVRp22 genome based on a full-length sequence comparison with the RVRp13, VR2332, and MLV genomes.",,"['Khatun, Amina', 'Shabir, Nadeem', 'Seo, Byoung-Joo', 'Kim, Bum-Seok', 'Yoon, Kyoung-Jin', 'Kim, Won-Il']",,,,
,PMC,Differential Expression of the Middle East Respiratory Syndrome Coronavirus Receptor in the Upper Respiratory Tracts of Humans and Dromedary Camels,http://dx.doi.org/10.1128/JVI.02994-15,PMC4836314,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) is not efficiently transmitted between humans, but it is highly prevalent in dromedary camels. Here we report that the MERS-CoV receptor—dipeptidyl peptidase 4 (DPP4)—is expressed in the upper respiratory tract epithelium of camels but not in that of humans. Lack of DPP4 expression may be the primary cause of limited MERS-CoV replication in the human upper respiratory tract and hence restrict transmission.",,"['Widagdo, W.', 'Raj, V. Stalin', 'Schipper, Debby', 'Kolijn, Kimberley', 'van Leenders, Geert J. L. H.', 'Bosch, Berend J.', 'Bensaid, Albert', 'Segalés, Joaquim', 'Baumgärtner, Wolfgang', 'Osterhaus, Albert D. M. E.', 'Koopmans, Marion P.', 'van den Brand, Judith M. A.', 'Haagmans, Bart L.']",,,,
,PMC,The C-Terminal Tail of TRIM56 Dictates Antiviral Restriction of Influenza A and B Viruses by Impeding Viral RNA Synthesis,http://dx.doi.org/10.1128/JVI.03172-15,PMC4836312,,,"Accumulating data suggest that tripartite-motif-containing (TRIM) proteins participate in host responses to viral infections, either by acting as direct antiviral restriction factors or through regulating innate immune signaling of the host. Of >70 TRIMs, TRIM56 is a restriction factor of several positive-strand RNA viruses, including three members of the family Flaviviridae (yellow fever virus, dengue virus, and bovine viral diarrhea virus) and a human coronavirus (OC43), and this ability invariably depends upon the E3 ligase activity of TRIM56. However, the impact of TRIM56 on negative-strand RNA viruses remains unclear. Here, we show that TRIM56 puts a check on replication of influenza A and B viruses in cell culture but does not inhibit Sendai virus or human metapneumovirus, two paramyxoviruses. Interestingly, the anti-influenza virus activity was independent of the E3 ligase activity, B-box, or coiled-coil domain. Rather, deletion of a 63-residue-long C-terminal-tail portion of TRIM56 abrogated the antiviral function. Moreover, expression of this short C-terminal segment curtailed the replication of influenza viruses as effectively as that of full-length TRIM56. Mechanistically, TRIM56 was found to specifically impede intracellular influenza virus RNA synthesis. Together, these data reveal a novel antiviral activity of TRIM56 against influenza A and B viruses and provide insights into the mechanism by which TRIM56 restricts these medically important orthomyxoviruses. IMPORTANCE Options to treat influenza are limited, and drug-resistant influenza virus strains can emerge through minor genetic changes. Understanding novel virus-host interactions that alter influenza virus fitness may reveal new targets/approaches for therapeutic interventions. We show here that TRIM56, a tripartite-motif protein, is an intrinsic host restriction factor of influenza A and B viruses. Unlike its antiviral actions against positive-strand RNA viruses, the anti-influenza virus activity of TRIM56 was independent of the E3 ligase activity. Rather, expression of a short segment within the very C-terminal tail of TRIM56 inhibited the replication of influenza viruses as effectively as that of full-length TRIM56 by specifically targeting viral RNA synthesis. These data reveal the remarkable multifaceted activity of TRIM56, which has developed multiple domains to inhibit multiple viral families. They also raise the possibility of developing a broad-spectrum, TRIM56-based antiviral approach for addition to influenza prophylaxis and/or control strategies.",,"['Liu, Baoming', 'Li, Nan L.', 'Shen, Yang', 'Bao, Xiaoyong', 'Fabrizio, Thomas', 'Elbahesh, Husni', 'Webby, Richard J.', 'Li, Kui']",,,,
,PMC,T cell-derived interleukin-10 is an important regulator of the Th17 response during lethal alphavirus encephalomyelitis,http://dx.doi.org/10.1016/j.jneuroim.2016.04.010,PMC4884611,,,"Neuroadapted Sindbis virus infection of mice causes T cell-mediated fatal encephalomyelitis. In the absence of IL-10, pathogenic Th17 cells are increased and disease is accelerated. Lymphoid and myeloid cell contributions to IL-10 production were determined using VertX IL-10 transcriptional eGFP reporter mice. Effector and regulatory CD4(+) and CD8(+) T cells in the brain, but not the cervical lymph nodes, were the primary producers of IL-10. Th17 and Th1/Th17 cells were increased in mice that lacked T cell IL-10 production, although less than in the absence of IL-10. Morbidity and mortality were not affected suggesting an IL-10 threshold for disease exacerbation.",,"['Kulcsar, Kirsten A.', 'Griffin, Diane E.']",,,,
,PMC,Development of a candidate reference material for adventitious virus detection in vaccine and biologicals manufacturing by deep sequencing,http://dx.doi.org/10.1016/j.vaccine.2015.12.020,PMC4823300,26709640,CC BY-NC-ND,"BACKGROUND: Unbiased deep sequencing offers the potential for improved adventitious virus screening in vaccines and biotherapeutics. Successful implementation of such assays will require appropriate control materials to confirm assay performance and sensitivity. METHODS: A common reference material containing 25 target viruses was produced and 16 laboratories were invited to process it using their preferred adventitious virus detection assay. RESULTS: Fifteen laboratories returned results, obtained using a wide range of wet-lab and informatics methods. Six of 25 target viruses were detected by all laboratories, with the remaining viruses detected by 4–14 laboratories. Six non-target viruses were detected by three or more laboratories. CONCLUSION: The study demonstrated that a wide range of methods are currently used for adventitious virus detection screening in biological products by deep sequencing and that they can yield significantly different results. This underscores the need for common reference materials to ensure satisfactory assay performance and enable comparisons between laboratories.",2016 Apr 12,"['Mee, Edward T.', 'Preston, Mark D.', 'Minor, Philip D.', 'Schepelmann, Silke', None]",Vaccine,,,
,PMC,Rasch Analysis of The WURSS-21 Dimensional Validation and Assessment of Invariance,,PMC5089813,,,"BACKGROUND: The purpose of this study is to use Rasch analysis to explore the validity of considering self-report scores from Wisconsin Upper Respiratory Symptom Survey (WURSS-21) as a single global illness severity domain. The WURSS-21 is a widely used questionnaire instrument that assesses symptom severity and functional impact of common cold and flu-like illness. METHODS: This study applies item response theory, specifically Rasch modeling, to investigate dimensional and measurement properties of the WURSS-21, and looks at invariance over time. The data assessed represents 1167 people, each scoring the WURSS-21 once daily for up to seven consecutive days of acute upper respiratory infection (URI) illness. RESULTS: Rasch analysis supports a single domain WURSS-21 global symptom score. Assessment of differential item functioning across seven days of illness provides evidence for measurement invariance. While individual items rating physical symptoms were somewhat variable, items rating functional impairment and quality of life impact appeared quite consistent across a single domain over seven days of illness. CONCLUSION: Rasch analysis of WURSS-21 items provides evidential support for a single invariant domain. These findings support the practice of using a simply summed daily global illness severity score to represent the overall symptomatic and functional impairments arising from URI.",,"['Brown, Roger L.', 'Obasi, Chidi N.', 'Barrett, Bruce']",,,,
,PMC,Inherited and acquired disorders of myelin: the underling myelin pathology,http://dx.doi.org/10.1016/j.expneurol.2016.04.002,PMC5010953,,,"Remyelination is a major therapeutic goal in human myelin disorders, serving to restore function to demyelinated axons and providing neuroprotection. The target disorders that might be amenable to the promotion of this repair process are diverse and increasing in number. They range primarily from those of genetic, inflammatory to toxic origin. In order to apply remyelinating strategies to these disorders, it is essential to know whether the myelin damage results from a primary attack on myelin or the oligodendrocyte or both, and whether indeed these lead to myelin breakdown and demyelination. In some disorders, myelin sheath abnormalities are prominent but demyelination does not occur. This review explores the range of human and animal disorders where myelin pathology exists and focusses on defining the myelin changes in each and their cause, to help define whether they are targets for myelin repair therapy.",,"['Duncan, Ian D.', 'Radcliff, Abigail B.']",,,,
,PMC,The role of imaging in diagnosis and management of femoral head avascular necrosis,http://dx.doi.org/10.11138/ccmbm/2015.12.3s.031,PMC4832402,,,"The aim of this paper is to critically review the literature documenting the imaging approach in adult Femoral Head Avascular Necrosis (FHAVN). For this purpose we described and evaluated different radiological techniques, such as X-ray, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Nuclear Medicine. Plain films are considered the first line imaging technique due to its ability to depict femoral head morphological changes, to its low costs and high availability. CT is not a routinely performed technique, but is useful to rule out the presence of a subchondral fracture when MRI is doubtful or contraindicated. MRI is unanimously considered the gold standard technique in the early stages, being capable to detect bone marrow changes such as edema and sclerosis. It may be useful also to guide treatment and, as CT, it is a validated technique in follow-up of patients with FHAVN. Nuclear medicine imaging is mostly applied in post-operative period to detect graft viability or infective complications. More advanced techniques may be useful in particular conditions but still need to be validated; thus new research trials are desirable. In conclusion, X-ray examination is the first line approach, but lacks of sensitivity in early stage whereas MRI is indicated. CT easily depicts late stage deformation and may decrease MRI false positive results in detecting the subchondral fracture. However, the role of both Nuclear Medicine Imaging and advanced MR techniques in FHAVN still need to be investigated.",,"['Manenti, Guglielmo', 'Altobelli, Simone', 'Pugliese, Luca', 'Tarantino, Umberto']",,,,
,PMC,Impact of Infection Prevention and Control Initiatives on Acute Respiratory Infections in a Pediatric Long-Term Care Facility,http://dx.doi.org/10.1017/ice.2016.73,PMC5108294,,,"We evaluated the collective impact of several infection prevention and control initiatives aimed at reducing acute respiratory infections (ARIs) in a pediatric long-term care facility. ARIs did not decrease overall, though the proportion of infections associated with outbreaks and average number of cases per outbreak decreased. Influenza rates decreased significantly.",,"['Murray, Meghan T.', 'Jackson, Olivia', 'Cohen, Bevin', 'Hutcheon, Gordon', 'Saiman, Lisa', 'Larson, Elaine', 'Neu, Natalie']",,,,
,PMC,MIDDLE EAST RESPIRATORY SYNDROME VACCINES,http://dx.doi.org/10.1016/j.ijid.2016.04.008,PMC4969153,,,"The Middle East Respiratory Syndrome-coronavirus (MERS-CoV) has infected over 1600 individuals with nearly 600 deaths since it was first identified in human populations in 2012. No anti-viral therapies or vaccines for treatment and prophylaxis are available. Here, we discuss approaches to developing MERS vaccines, including a summary of previous efforts to develop vaccines useful against human and non-human coronaviruses. A striking feature of MERS is the important role that camels have in transmission. Camel vaccination may be a novel approach to preventing the human infection.",,"['Perlman, Stanley', 'Vijay, Rahul']",,,,
,PMC,Visualization of Data Regarding Infections Using Eye Tracking Techniques,http://dx.doi.org/10.1111/jnu.12204,PMC4939395,,,"OBJECTIVE: To evaluate ease of use and usefulness for nurses of visualizations of infectious disease transmission in a hospital. DESIGN: An observational study was used to evaluate perceptions of several visualizations of data extracted from electronic health records designed using a participatory approach. Twelve nurses in the master’s program in an urban research-intensive nursing school participated in May 2015. METHODS: A convergent parallel mixed method was used to evaluate nurses’ perceptions on ease of use and usefulness of five visualization conveying trends in hospital infection transmission applying think-aloud, interview, and eye-tracking techniques. FINDINGS: Subjective data from the interview and think-aloud techniques indicated that participants preferred the traditional line graphs in simple data representation due to their familiarity, clarity, and easiness to read. An objective quantitative measure of eye movement analysis (444,421 gaze events) identified a high degree of participants’ attention span in infographics in all three scenarios. All participants responded with the correct answer within 1 min in comprehensive tests. CONCLUSIONS: A user-centric approach was effective in developing and evaluating visualizations for hospital infection transmission. For the visualizations designed by the users, the participants were easily able to comprehend the infection visualizations on both line graphs and infographics for simple visualization. The findings from the objective comprehension test and eye movement and subjective attitudes support the feasibility of integrating user-centric visualization designs into electronic health records, which may inspire clinicians to be mindful of hospital infection transmission. Future studies are needed to investigate visualizations and motivation, and the effectiveness of visualization on infection rate. CLINICAL RELEVANCE: This study designed visualization images using clinical data from electronic health records applying a user-centric approach. The design insights can be applied for visualizing patient data in electronic health records.",,"['Yoon, Sunmoo', 'Cohen, Bevin', 'Cato, Kenrick D.', 'Liu, Jianfang', 'Larson, Elaine L.']",,,,
,PMC,Fusion of Enveloped Viruses in Endosomes,http://dx.doi.org/10.1111/tra.12389,PMC4866878,,,"Ari Helenius launched the field of enveloped virus fusion in endosomes with a seminal paper in the Journal of Cell Biology in 1980. In the intervening years a great deal has been learned about the structures and mechanisms of viral membrane fusion proteins as well as about the endosomes in which different enveloped viruses fuse and the endosomal cues that trigger fusion. We now recognize three classes of viral membrane fusion proteins based on structural criteria and four mechanisms of fusion triggering. After reviewing general features of viral membrane fusion proteins and viral fusion in endosomes, we delve into three characterized mechanisms for viral fusion triggering in endosomes: by low pH, by receptor binding plus low pH, and by receptor binding plus the action of a protease. We end with a discussion of viruses that may employ novel endosomal fusion triggering mechanisms. A key take home message is that enveloped viruses that enter cells by fusing in endosomes traverse the endocytic pathway until they reach an endosome that has all of the environmental conditions (pH, proteases, ions, intracellular receptors, and lipid composition) to (if needed) prime and (in all cases) trigger the fusion protein and to support membrane fusion.",,"['White, Judith M.', 'Whittaker, Gary R.']",,,,
,PMC,An Improved Ward Architecture for Treatment of Patients with Ebola Virus Disease in Liberia,http://dx.doi.org/10.4269/ajtmh.15-0209,PMC4824206,,,"During the recent outbreak of Ebola virus disease (EVD) in west Africa, we established an Ebola treatment center (ETC) with improved ward architecture. The ETC was built with movable prefabricated boards according to infectious disease unit standard requirements. The clinical staff ensured their own security while providing patients with effective treatment. Of the 180 admissions to the ETC, 10 cases were confirmed with EVD of which six patients survived. None of the clinical staff was infected. We hope that our experience will enable others to avoid unnecessary risks while delivering EVD care.",,"['You, Jianping', 'Mao, Qing']",,,,
,PMC,Vaccines for the prevention against the threat of MERS-CoV,http://dx.doi.org/10.1586/14760584.2016.1167603,PMC5097835,,,"First identified in 2012, Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is listed as a new Category C Priority Pathogen. While the high mortality of MERS-CoV infection is further intensified by potential human-to-human transmissibility, no MERS vaccines are available for human use. This review explains immune responses resulting from MERS-CoV infection, describes MERS vaccine criteria, and presents available small animal models to evaluate the efficacy of MERS vaccines. Current advances in vaccine development are summarized, focusing on specific applications and limitations of each vaccine category. Taken together, this review provides valuable guidelines toward the development of an effective and safe MERS vaccine. This article is written for a Special Focus Issue of Expert Review of Vaccines on “Vaccines for Biodefence”.",,"['Du, Lanying', 'Tai, Wanbo', 'Zhou, Yusen', 'Jiang, Shibo']",,,,
,PMC,"Prevention and Treatment of Influenza, Influenza-Like Illness, and Common Cold by Herbal, Complementary, and Natural Therapies",http://dx.doi.org/10.1177/2156587216641831,PMC5871211,,,"In recent years viral respiratory tract infections, especially influenza viruses, have had a major impact on communities worldwide as a result of unavailability of effective treatment or vaccine. The frequent alterations in the antigenic structures of respiratory viruses, particularly for RNA viruses, pose difficulties in production of effective vaccines. The unavailability of optimal medication and shortage of effective vaccines suggests the requirement for alternative natural therapies. Several herbal remedies were used for prevention and treatment viral respiratory illnesses. Among those that were found effective included maoto, licorice roots, antiwei, North American ginseng, berries, Echinacea, plants extracted carnosic acid, pomegranate, guava tea, and Bai Shao. There is scientific evidence regarding the effectiveness of several complementary therapies for colds. Oral zinc may reduce the length and severity of a cold. Taking vitamin C supplements on a regular basis only slightly reduces the length and severity of colds. Probiotics were found better than placebo in reducing the number episodes of acute upper respiratory tract infections, the rate of episodes of acute upper respiratory tract infection and reducing antibiotic use. Alkaline diets or drinks might have antiviral properties as in vitro studies demonstrated inactivation effect of alkaline medium on respiratory virus. Earthing might have a natural anti-inflammatory effect for human body. It is now accepted that an overwhelming inflammatory response is the cause of human deaths from avian H5N1 influenza infection. Earthing accelerates immune response following vaccination, as demonstrated by increases of gamma globulin concentration. No in vivo or clinical studies were found that investigate the role of alkalization or earthing on respiratory viral infections. Thus, future studies are recommended to reveal any potential curative effects.",,"Mousa, Haider Abdul-Lateef",,,,
,PMC,A novel antibody discovery platform identifies anti-influenza A broadly neutralizing antibodies from human memory B cells,http://dx.doi.org/10.1080/19420862.2016.1170263,PMC4968088,,,"Monoclonal antibody isolation directly from circulating human B cells is a powerful tool to delineate humoral responses to pathological conditions and discover antibody therapeutics. We have developed a platform aimed at improving the efficiencies of B cell selection and V gene recovery. Here, memory B cells are activated and amplified using Epstein-Barr virus infection, co-cultured with CHO-muCD40L cells, and then assessed by functional screenings. An in vitro transcription and translation (IVTT) approach was used to analyze variable (V) genes recovered from each B cell sample and identify the relevant heavy/light chain pair(s). We achieved efficient amplification and activation of memory B cells, and eliminated the need to: 1) seed B cells at clonal level (≤1 cell/well) or perform limited dilution cloning; 2) immortalize B cells; or 3) assemble V genes into an IgG expression vector to confirm the relevant heavy/light chain pairing. Cross-reactive antibodies targeting a conserved epitope on influenza A hemagglutinin were successfully isolated from a healthy donor. In-depth analysis of the isolated antibodies suggested their potential uses as anti-influenza A antibody therapeutics and uncovered a distinct affinity maturation pathway. Importantly, our results showed that cognate heavy/light chain pairings contributed to both the expression level and binding abilities of our newly isolated VH1-69 family, influenza A neutralizing antibodies, contrasting with previous observations that light chains do not significantly contribute to the function of this group of antibodies. Our results further suggest the potential use of the IVTT as a powerful antibody developability assessment tool.",,"['Xiao, Xiaodong', 'Chen, Yan', 'Varkey, Reena', 'Kallewaard, Nicole', 'Koksal, Adem C.', 'Zhu, Qing', 'Wu, Herren', 'Chowdhury, Partha S.', ""Dall'Acqua, William F.""]",,,,
,PMC,Use of serological surveys to generate key insights into the changing global landscape of infectious disease,http://dx.doi.org/10.1016/S0140-6736(16)30164-7,PMC5678936,,,,,"['Metcalf, C Jessica E', 'Farrar, Jeremy', 'Cutts, Felicity T', 'Basta, Nicole E', 'Graham, Andrea L', 'Lessler, Justin', 'Ferguson, Neil M', 'Burke, Donald S', 'Grenfell, Bryan T']",,,,
,PMC,Long-range communication between different functional sites in the picornaviral 3C protein,http://dx.doi.org/10.1016/j.str.2016.02.019,PMC4824962,,,"The 3C protein is a master regulator of the picornaviral infection cycle, responsible for both cleaving viral and host proteins, and interacting with genomic RNA replication elements. Here we use nuclear magnetic resonance spectroscopy and molecular dynamics simulations to show that 3C is conformationally dynamic across multiple timescales. Binding of peptide and RNA lead to structural dynamics changes at both the protease active site and the RNA binding site, consistent with these sites being dynamically coupled. Indeed, binding of RNA influences protease activity, and likewise, interactions at the active site affect RNA binding. We propose that RNA and peptide binding reshapes the conformational energy landscape of 3C to regulate subsequent functions, including formation of complexes with other viral proteins. The observed channeling of the 3C energy landscape may be important for regulation of the viral infection cycle.",,"['Chan, Yan M.', 'Moustafa, Ibrahim M.', 'Arnold, Jamie J.', 'Cameron, Craig E.', 'Boehr, David D.']",,,,
,PMC,Aberrant coagulation causes a hyper-inflammatory response in severe influenza pneumonia,http://dx.doi.org/10.1038/cmi.2016.1,PMC4947825,,,"Influenza A virus (IAV) infects the respiratory tract in humans and causes significant morbidity and mortality worldwide each year. Aggressive inflammation, known as a cytokine storm, is thought to cause most of the damage in the lungs during IAV infection. Dysfunctional coagulation is a common complication in pathogenic influenza, manifested by lung endothelial activation, vascular leak, disseminated intravascular coagulation and pulmonary microembolism. Importantly, emerging evidence shows that an uncontrolled coagulation system, including both the cellular (endothelial cells and platelets) and protein (coagulation factors, anticoagulants and fibrinolysis proteases) components, contributes to the pathogenesis of influenza by augmenting viral replication and immune pathogenesis. In this review, we focus on the underlying mechanisms of the dysfunctional coagulatory response in the pathogenesis of IAV.",,"['Yang, Yan', 'Tang, Hong']",,,,
,PMC,Pathogen receptor discovery with a microfluidic human membrane protein array,http://dx.doi.org/10.1073/pnas.1518698113,PMC4843447,,,"The discovery of how a pathogen invades a cell requires one to determine which host cell receptors are exploited. This determination is a challenging problem because the receptor is invariably a membrane protein, which represents an Achilles heel in proteomics. We have developed a universal platform for high-throughput expression and interaction studies of membrane proteins by creating a microfluidic-based comprehensive human membrane protein array (MPA). The MPA is, to our knowledge, the first of its kind and offers a powerful alternative to conventional proteomics by enabling the simultaneous study of 2,100 membrane proteins. We characterized direct interactions of a whole nonenveloped virus (simian virus 40), as well as those of the hepatitis delta enveloped virus large form antigen, with candidate host receptors expressed on the MPA. Selected newly discovered membrane protein–pathogen interactions were validated by conventional methods, demonstrating that the MPA is an important tool for cellular receptor discovery and for understanding pathogen tropism.",,"['Glick, Yair', 'Ben-Ari, Ya’ara', 'Drayman, Nir', 'Pellach, Michal', 'Neveu, Gregory', 'Boonyaratanakornkit, Jim', 'Avrahami, Dorit', 'Einav, Shirit', 'Oppenheim, Ariella', 'Gerber, Doron']",,,,
,PMC,An Agent-Based Model of School Closing in Under-Vacccinated Communities During Measles Outbreaks,,PMC5032840,,,"The winter 2014–15 measles outbreak in the US represents a significant crisis in the emergence of a functionally extirpated pathogen. Conclusively linking this outbreak to decreases in the measles/mumps/rubella (MMR) vaccination rate (driven by anti-vaccine sentiment) is critical to motivating MMR vaccination. We used the NOVA modeling platform to build a stochastic, spatially-structured, individual-based SEIR model of outbreaks, under the assumption that R(0) ≈ 7 for measles. We show this implies that herd immunity requires vaccination coverage of greater than approximately 85%. We used a network structured version of our NOVA model that involved two communities, one at the relatively low coverage of 85% coverage and one at the higher coverage of 95%, both of which had 400-student schools embedded, as well as students occasionally visiting superspreading sites (e.g. high-density theme parks, cinemas, etc.). These two vaccination coverage levels are within the range of values occurring across California counties. Transmission rates at schools and superspreading sites were arbitrarily set to respectively 5 and 15 times background community rates. Simulations of our model demonstrate that a ‘send unvaccinated students home’ policy in low coverage counties is extremely effective at shutting down outbreaks of measles.",,"['Getz, Wayne M.', 'Carlson, Colin', 'Dougherty, Eric', 'Porco, Travis C.', 'Salter, Richard']",,,,
,PMC,An Expression of Clinical Significance: Exploring the Human Genome to Understand the Variable Response to Rhinovirus,http://dx.doi.org/10.1164/rccm.201511-2272ED,PMC4824935,,,,,"['Langelier, Charles', 'Christenson, Stephanie A.']",,,,
,PMC,Clinical Characteristics of Asthmatic Patients With Influenza-Like Illness and Risk for Severe Exacerbations in Mexico,http://dx.doi.org/10.1016/j.anai.2016.03.007,PMC4860073,,,,,"['Paulin-Prado, Paulina', 'Nishimura, Katherine', 'Freimanis-Hance, Laura', 'Hunsberger, Sally', 'Beigel, John', 'Fraga, Arturo Galindo', 'Hernandez, Ana A Ortiz', 'Llamosas-Gallardo, Beatriz', 'Moreno-Espinosa, Sarbelio', 'Magaña-Aquino, Martin', 'Palacios, Guillermo M Ruiz', 'Ramirez-Venegas, Alejandra']",,,,
,PMC,The Saudi Thoracic Society pneumococcal vaccination guidelines-2016,http://dx.doi.org/10.4103/1817-1737.177470,PMC4854068,27168856,CC BY-NC-SA,"Streptococcus pneumoniae (pneumococcus) is the leading cause of morbidity and mortality worldwide. Saudi Arabia is a host to millions of pilgrims who travel annually from all over the world for Umrah and the Hajj pilgrimages and are at risk of developing pneumococcal pneumonia or invasive pneumococcal disease (IPD). There is also the risk of transmission of S. pneumoniae including antibiotic resistant strains between pilgrims and their potential global spread upon their return. The country also has unique challenges posed by susceptible population to IPD due to people with hemoglobinopathies, younger age groups with chronic conditions, and growing problem of antibiotic resistance. Since the epidemiology of pneumococcal disease is constantly changing, with an increase in nonvaccine pneumococcal serotypes, vaccination policies on the effectiveness and usefulness of vaccines require regular revision. As part of the Saudi Thoracic Society (STS) commitment to promote the best practices in the field of respiratory diseases, we conducted a review of S. pneumoniae infections and the best evidence base available in the literature. The aim of the present study is to develop the STS pneumococcal vaccination guidelines for healthcare workers in Saudi Arabia. We recommend vaccination against pneumococcal infections for all children <5 years old, adults ≥50 years old, and people ≥6 years old with certain risk factors. These recommendations are based on the presence of a large number of comorbidities in Saudi Arabia population <50 years of age, many of whom have risk factors for contracting pneumococcal infections. A section for pneumococcal vaccination before the Umrah and Hajj pilgrimages is included as well.",2016 Apr-Jun,"['Alharbi, N. S.', 'Al-Barrak, A. M.', 'Al-Moamary, M. S.', 'Zeitouni, M. O.', 'Idrees, M. M.', 'Al-Ghobain, M. O.', 'Al-Shimemeri, A. A.', 'Al-Hajjaj, Mohamed S.']",Ann Thorac Med,,,
,PMC,Influenza immunization and surveillance in Saudi Arabia,http://dx.doi.org/10.4103/1817-1737.180022,PMC4854065,27168867,CC BY-NC-SA,,2016 Apr-Jun,"Hashem, Anwar M.",Ann Thorac Med,,,
,PMC,Patient characteristics infected with Middle East respiratory syndrome coronavirus infection in a tertiary hospital,http://dx.doi.org/10.4103/1817-1737.180027,PMC4854059,27168861,CC BY-NC-SA,"BACKGROUND: In April 2014, a surge in cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was seen in Jeddah, Saudi Arabia. The aim of this study is to describe the demographic and clinical features, laboratory and radiological findings of MERS-CoV patients identified during this outbreak in a single tertiary hospital. METHODS: All laboratory-confirmed MERS-CoV cases who presented to King Faisal Specialist Hospital from March 1, 2014, to May 30, 2014, were identified. Patients' charts were reviewed for demographic information, comorbidities, clinical presentations, and outcomes. RESULTS: A total of 39 patients with confirmed MERS-CoV infection were identified. Twenty-one were male (54%), aged 40 ± 19 years and included 3 (8%) pediatric patients (<18-year-old). 16 (41%) patients were health care workers. Twenty-one (53%) patients were previously healthy whereas eighteen (47%) had at least one comorbidity. The predominant comorbidities included hypertension (31%), diabetes (26%), respiratory (23%), and renal disease (18%). Thirty patients (81%) were symptomatic at presentation, fever (69%) being the most common complaint. The overall mortality rate was 28%. In univariate analysis, older age, hypertension, and chronic kidney disease were associated with mortality. CONCLUSIONS: MERS-CoV presentation varies from asymptomatic infection to severe respiratory disease causing death. Future studies to identify the risk factors for worse outcome are needed.",2016 Apr-Jun,"['Alraddadi, Basem', 'Bawareth, Noha', 'Omar, Haneen', 'Alsalmi, Hanadi', 'Alshukairi, Abeer', 'Qushmaq, Ismael', 'Feteih, Maun', 'Qutob, Mohammed', 'Wali, Ghassan', 'Khalid, Imran']",Ann Thorac Med,,,
,PMC,PubMed-cited research articles on the Middle East respiratory syndrome,http://dx.doi.org/10.4103/1817-1737.180024,PMC4854056,27168858,CC BY-NC-SA,,2016 Apr-Jun,"['Arabi, Yaseen', 'Deeb, Ahmad M.', 'Aqeel, Hanan', 'Balkhy, Hanan']",Ann Thorac Med,,,
,PMC,Defining Neonatal Sepsis,http://dx.doi.org/10.1097/MOP.0000000000000315,PMC4786443,,,"PURPOSE OF THE REVIEW: Although infection rates have modestly decreased in the neonatal intensive care unit (NICU) as a result of ongoing quality improvement measures, neonatal sepsis remains a frequent and devastating problem among hospitalized preterm neonates. Despite multiple attempts to address this unmet need, there have been minimal advances in clinical management, outcomes, and accuracy of diagnostic testing options over the last three decades. One strong contributor to a lack of medical progress is a variable case definition of disease. The inability to agree on a precise definition greatly reduces the likelihood of aligning findings from epidemiologists, clinicians, and researchers, which, in turn, severely hinders progress towards improving outcomes. RECENT FINDINGS: Pediatric consensus definitions for sepsis are not accurate in term infants and are not appropriate for preterm infants. In contrast to the defined multi-stage criteria for other devastating diseases encountered in the NICU (e.g., bronchopulmonary dysplasia), there is significant variability in the criteria used by investigators to substantiate the diagnosis of neonatal sepsis. SUMMARY: The lack of an accepted consensus definition for neonatal sepsis impedes our efforts towards improved diagnostic and prognostic options as well as accurate outcomes information for this vulnerable population.",,"Wynn, James L.",,,,
,PMC,Correspondence: Ebola Virus Disease in ASEAN Countries,http://dx.doi.org/10.7860/JCDR/2016/17673.7546,PMC4866172,,,,,"['Joob, Beuy', 'Wiwanitkit, Viroj']",,,,
,PMC,Extracellular vesicles: masters of intercellular communication and potential clinical interventions,http://dx.doi.org/10.1172/JCI87316,PMC4811136,,,"Intercellular signaling via extracellular vesicles (EVs) is an underappreciated modality of cell-cell crosstalk that enables cells to convey packages of complex instructions to specific recipient cells. EVs transmit these instructions through their cargoes of multiple proteins, nucleic acids, and specialized lipids, which are derived from their cells of origin and allow for combinatorial effects upon recipient cells. This Review series brings together the recent progress in our understanding of EV signaling in physiological and pathophysiological conditions, highlighting how certain EVs, particularly exosomes, can promote or regulate infections, host immune responses, development, and various diseases — notably cancer. Given the diverse nature of EVs and their abilities to profoundly modulate host cells, this series puts particular emphasis on the clinical applications of EVs as therapeutics and as diagnostic biomarkers.",,"['Pitt, Jonathan M.', 'Kroemer, Guido', 'Zitvogel, Laurence']",,,,
,PMC,Extracellular vesicles and infectious diseases: new complexity to an old story,http://dx.doi.org/10.1172/JCI81132,PMC4811125,,,"Exosomes and other extracellular microvesicles (ExMVs) have important functions in intercellular communication and regulation. During the course of infection, these vesicles can convey pathogen molecules that serve as antigens or agonists of innate immune receptors to induce host defense and immunity, or that serve as regulators of host defense and mediators of immune evasion. These molecules may include proteins, nucleic acids, lipids, and carbohydrates. Pathogen molecules may be disseminated by incorporation into vesicles that are created and shed by host cells, or they may be incorporated into vesicles shed from microbial cells. Involvement of ExMVs in the induction of immunity and host defense is widespread among many pathogens, whereas their involvement in immune evasion mechanisms is prominent among pathogens that establish chronic infection and is found in some that cause acute infection. Because of their immunogenicity and enrichment of pathogen molecules, exosomes may also have potential in vaccine preparations and as diagnostic markers. Additionally, the ability of exosomes to deliver molecules to recipient cells raises the possibility of their use for drug/therapy delivery. Thus, ExMVs play a major role in the pathogenesis of infection and provide exciting potential for the development of novel diagnostic and therapeutic approaches.",,"['Schorey, Jeffrey S.', 'Harding, Clifford V.']",,,,
,PMC,Crystal structure of the mouse hepatitis virus ns2 phosphodiesterase domain that antagonizes RNase L activation,http://dx.doi.org/10.1099/jgv.0.000395,PMC5974288,,,"Prior studies have demonstrated that the mouse hepatitis virus (MHV) A59 strain ns2 protein is a member of the 2H phosphoesterase family and exhibits 2′,5′-phosphodiesterase (PDE) activity. During the IFN antiviral response, ns2 cleaves 2′,5′-oligoadenylate (2-5A), a key mediator of RNase L activation, thereby subverting the activation of RNase L and evading host innate immunity. However, the mechanism of 2-5A cleavage by ns2 remains unclear. Here, we present the crystal structure of the MHV ns2 PDE domain and demonstrate a PDE fold similar to that of the cellular protein, a kinase anchoring protein 7 central domain (AKAP7(CD)) and rotavirus VP3 carboxy-terminal domain. The structure displays a pair of strictly conserved HxT/Sx motifs and forms a deep, positively charged catalytic groove with β-sheets and an arginine-containing loop. These findings provide insight into the structural basis for 2-5A binding of MHV ns2.",,"['Sui, Baokun', 'Huang, Junhua', 'Jha, Babal K.', 'Yin, Ping', 'Zhou, Ming', 'Fu, Zhen F.', 'Silverman, Robert H.', 'Weiss, Susan R.', 'Peng, Guiqing', 'Zhao, Ling']",,,,
,PMC,Acute Otitis Media and Other Complications of Viral Respiratory Infection,http://dx.doi.org/10.1542/peds.2015-3555,PMC4811317,,,"BACKGROUND: Viral upper and lower respiratory tract infections (URI, LRI) are common in infants. We determined the prevalence of viral URI and its complications, including acute otitis media (AOM) and LRI, and assessed the effect of bacterial-viral interactions, and genetic and environmental risks on AOM development. METHODS: Healthy infants were enrolled from near birth and followed to the first episode of AOM up to 12 months of age. Nasopharyngeal specimens were collected at monthly intervals (months 1–6, 9) and during viral URI episodes for bacterial culture and viral polymerase chain reaction studies. Subjects were followed closely for AOM development. RESULTS: A total of 367 infants were followed for 286 child-years; 887 URI (305 infants) and 180 AOM episodes (143 infants) were documented. Prevalence of URI, LRI, and AOM in the first year was 3.2, 0.25, and 0.67 per child-year, respectively. Cumulative AOM incidence by ages 3, 6, and 12 months was 6%, 23%, and 46%. Infants with and without AOM had 4.7 and 2.3 URI episodes per child-year, respectively (P < .002). Pathogenic bacterial colonization rates by month were significantly higher in infants with AOM (P < .005). Breastfeeding reduced both URI and AOM risks (P < .05). Significant bacterial-viral interactions occurred with Moraxella catarrhalis and a variety of respiratory viruses and altered URI and AOM risks. CONCLUSIONS: Almost half of infants experienced AOM by age 1. Important AOM risk factors included frequent viral URI, pathogenic bacterial colonization, and lack of breastfeeding. Bacterial-viral interactions may play a significant role in AOM pathogenesis and deserve further investigation.",,"['Chonmaitree, Tasnee', 'Trujillo, Rocio', 'Jennings, Kristofer', 'Alvarez-Fernandez, Pedro', 'Patel, Janak A.', 'Loeffelholz, Michael J.', 'Nokso-Koivisto, Johanna', 'Matalon, Reuben', 'Pyles, Richard B.', 'Miller, Aaron L.', 'McCormick, David P.']",,,,
,PMC,Severe Pneumonia Treated Succesfully with Levofloxacin and Oseltamivir During Flu Epidemic,http://dx.doi.org/10.5578/ttj.17.2.018,PMC5792124,,,"Viral pneumonia is an important cause of community acquired pneumonias (CAP). It’s not only specific to childhood period. Although immunocompromised adults are susceptible; all young and healthy adults are at risk. Viral pneumonias are usually underestimated due to lack of diagnostic modalities so a clinician must be aware of. Co-infection of viruses and bacteria is not uncommon and can be mortal especially in a flu epidemic, therefore, in the absence of diagnostic tools initiating to anti-viral treatment without delay is important.",,"['Kabalak, Pınar Akın', 'Esenkaya, Asım']",,,,
,PMC,Quantitative effects of a declaration of a state of emergency on foot-and-mouth disease,http://dx.doi.org/10.1007/s12199-016-0517-3,PMC4907930,,,"OBJECTIVES: The law in Japan requires the declaration of a state of emergency and implementation of countermeasures for an epidemic of a new infectious disease. However, because a state of emergency has never been declared in Japan, its effects remain unknown. The required countermeasures are similar to those implemented in the foot-and-mouth disease epidemic in Miyazaki in 2010. This study aimed to quantitatively estimate the effect of the declaration in 2010 and investigate the nature of the epidemic based on the day on which the declaration took effect. METHODS: Only publicly available data were used. Data for farms in the most affected town were analyzed. A modified susceptible–infected–recovered model was used to estimate the effect and for the simulation. Another model was used to estimate the effective reproduction number. RESULTS: After the declaration, the intra-bovine transmission rate decreased by 18.1 %, and there were few days when the effective reproduction number was >1.0. A few weeks delay in the declaration significantly increased the possibility of epidemic, number of farms at peak, and final infection scale. CONCLUSIONS: Based on the substantial decrease in the transmission rate after the declaration of a state of emergency in 2010, a future declaration will have a similar effect for a new infectious disease even though a direct extrapolation is not valid. Although a declaration should be carefully considered owing to the potential socioeconomic effects, it is essential to prepare for the implementation given that a delay of only a few weeks should be acceptable.",,"['Yamauchi, Takenori', 'Takeuchi, Shouhei', 'Horii, Yoichiro', 'Yamano, Yuko', 'Kuroda, Yoshiki', 'Nakadate, Toshio']",,,,
,PMC,The Point-of-Care Laboratory in Clinical Microbiology,http://dx.doi.org/10.1128/CMR.00090-15,PMC4861988,,,"Point-of-care (POC) laboratories that deliver rapid diagnoses of infectious diseases were invented to balance the centralization of core laboratories. POC laboratories operate 24 h a day and 7 days a week to provide diagnoses within 2 h, largely based on immunochromatography and real-time PCR tests. In our experience, these tests are conveniently combined into syndrome-based kits that facilitate sampling, including self-sampling and test operations, as POC laboratories can be operated by trained operators who are not necessarily biologists. POC laboratories are a way of easily providing clinical microbiology testing for populations distant from laboratories in developing and developed countries and on ships. Modern Internet connections enable support from core laboratories. The cost-effectiveness of POC laboratories has been established for the rapid diagnosis of tuberculosis and sexually transmitted infections in both developed and developing countries.",,"['Drancourt, Michel', 'Michel-Lepage, Audrey', 'Boyer, Sylvie', 'Raoult, Didier']",,,,
,PMC,Vaccinology in the third millennium: scientific and social challenges,http://dx.doi.org/10.1016/j.coviro.2016.03.003,PMC4902778,,,"The epidemiology of deaths due to vaccine-preventable diseases has been significantly and positively altered through the use of vaccines. Despite this, significant challenges remain in vaccine development and use in the third millennium. Both new (Ebola, Chikungunya, West Nile) and re-emerging diseases (measles, mumps, influenza) require the development of new or next-generation vaccines. The global aging of the population, and accumulating numbers of immunocompromised persons, will require new vaccine and adjuvant development to protect large segments of the population. After vaccine development, significant challenges remain globally in the cost and efficient use and acceptance of vaccines by the public. This article raises issues in these two areas and suggests a way forward that will benefit current and future generations.",,"['Poland, Gregory A.', 'Whitaker, Jennifer A.', 'Poland, Caroline M.', 'Ovsyannikova, Inna G.', 'Kennedy, Richard B.']",,,,
,PMC,Impact of Multiplex Polymerase Chain Reaction Testing for Respiratory Pathogens on Healthcare Resource Utilization for Pediatric Inpatients,http://dx.doi.org/10.1016/j.jpeds.2016.02.050,PMC5452417,,,"OBJECTIVE: To assess whether multiplex polymerase chain reaction (mPCR) vs. non-MPCR testing impacts the use of antibiotics, chest radiographs, and isolation precautions. STUDY DESIGN: We retrospectively compared use of antibiotics, chest radiographs, and isolation precautions for patients <18 years old (excluding neonates) hospitalized at a tertiary referral center tested for respiratory pathogens in the emergency department or during the first 2 hospital days, during two periods: June 2010–June 2012 (non-MPCR group) vs. October 2012-May 2014 (MPCR group). RESULTS: Subjects (n=2430) in the MPCR group were older, had more complex chronic conditions, and were admitted to the PICU more often compared with the non-MPCR (n=2349) group. Subjects in the MPCR group had more positive tests (42.4% vs. 14.4%, p<0.01), received fewer days of antibiotics (4 vs. 5 median antibiotic days, p<0.01), fewer chest radiographs performed, (59% vs. 78%, p<0.01), and were placed in isolation longer (20 vs. 0 median isolation-hours, p<0.01) compared with the non-MPCR group. In multivariable regression, patients tested with MPCR were less likely to receive antibiotics for ≥2 days (OR 0.5, 95% CI 0.5-0.6), chest radiographs at admission (OR 0.4, 95% CI 0.3-0.4), and more likely to be in isolation for ≥2 days (OR 2.4, 95% CI 2.1-2.8 compared with the non- MPCR group. CONCLUSIONS: Use of MPCR testing for respiratory viruses among hospitalized patients was significantly associated with decreased healthcare resource utilization, including decreased use of antibiotics and chest radiographs, and increased use of isolation precautions.",,"['Subramony, Anupama', 'Zachariah, Philip', 'Krones, Ariella', 'Whittier, Susan', 'Saiman, Lisa']",,,,
,PMC,"Functionalized N,N-Diphenylamines as Potent and Selective EPAC2 Inhibitors",http://dx.doi.org/10.1021/acsmedchemlett.5b00477,PMC4867506,,,"[Image: see text] N,N-Diphenylamines were discovered as potent and selective EPAC2 inhibitors. A study was conducted to determine the structure–activity relationships in a series of inhibitors of which several compounds displayed submicromolar potencies. Selectivity over the related EPAC1 protein was also demonstrated. Computational modeling reveals an allosteric site that is distinct from the cAMP binding domain shared by both EPAC isoforms, providing a theory with regards to subtype selectivity.",,"['Wild, Christopher\nT.', 'Zhu, Yingmin', 'Na, Ye', 'Mei, Fang', 'Ynalvez, Marcus\nA.', 'Chen, Haiying', 'Cheng, Xiaodong', 'Zhou, Jia']",,,,
,PMC,Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses,http://dx.doi.org/10.1128/JVI.03049-15,PMC4810556,,,"Mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. Lassa virus (LASV), for example, is endemic in several West African countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. There are currently no FDA-licensed therapeutics or vaccines available to combat arenavirus infection. A hallmark of arenavirus infection (e.g., LASV) is general immunosuppression that contributes to high viremia. Here, we discuss the early host immune responses to arenavirus infection and the recently discovered molecular mechanisms that enable pathogenic viruses to suppress host immune recognition and to contribute to the high degree of virulence. We also directly compare the innate immune evasion mechanisms between arenaviruses and other hemorrhagic fever-causing viruses, such as Ebola, Marburg, Dengue, and hantaviruses. A better understanding of the immunosuppression and immune evasion strategies of these deadly viruses may guide the development of novel preventative and therapeutic options.",,"['Meyer, Bjoern', 'Ly, Hinh']",,,,
,PMC,The RNA- and TRIM25-Binding Domains of Influenza Virus NS1 Protein Are Essential for Suppression of NLRP3 Inflammasome-Mediated Interleukin-1β Secretion,http://dx.doi.org/10.1128/JVI.00120-16,PMC4810543,,,"Inflammasomes are cytosolic multimolecular protein complexes that stimulate the activation of caspase-1 and the release of mature forms of interleukin-1β (IL-1β) and IL-18. We previously demonstrated that the influenza A virus M2 protein stimulates IL-1β secretion following activation of the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. The nonstructural protein 1 (NS1) of influenza virus inhibits caspase-1 activation and IL-1β secretion. However, the precise mechanism by which NS1 inhibits IL-1β secretion remains unknown. Here, we showed that J774A.1 macrophages stably expressing the NS1 protein inhibited IL-1β secretion after infection with recombinant influenza virus lacking the NS1 gene. Coimmunoprecipitation assay revealed that the NS1 protein interacts with NLRP3. Importantly, the NS1 protein inhibited the NLRP3/ASC-induced single-speck formation required for full activation of inflammasomes. The NS1 protein of other influenza virus strains, including a recent pandemic strain, also inhibited inflammasome-mediated IL-1β secretion. The NS1 RNA-binding domain (basic residues 38 and 41) and TRIM25-binding domain (acidic residues 96 and 97) were required for suppression of NLRP3 inflammasome-mediated IL-1β secretion. These results shed light on a mechanism by which the NS1 protein of influenza virus suppresses NLRP3 inflammasome-mediated IL-1β secretion. IMPORTANCE Innate immune sensing of influenza virus via pattern recognition receptors not only plays a key role in generating type I interferons but also triggers inflammatory responses. We previously demonstrated that the influenza A virus M2 protein activates the NLRP3 inflammasome, leading to the secretion of interleukin-1β (IL-1β) and IL-18 following the activation of caspase-1. Although the nonstructural protein 1 (NS1) of influenza virus inhibits IL-1β secretion, the precise mechanism by which it achieves this remains to be defined. Here, we demonstrate that the NS1 protein interacts with NLRP3 to suppress NLRP3 inflammasome activation. J774A.1 macrophages stably expressing the NS1 protein suppressed NLRP3-mediated IL-1β secretion. The NS1 RNA-binding domain (basic residues 38 and 41) and TRIM25-binding domain (acidic residues 96 and 97) are important for suppression of NLRP3 inflammasome-mediated IL-1β secretion. These results will facilitate the development of new anti-inflammatory drugs.",,"['Moriyama, Miyu', 'Chen, I-Yin', 'Kawaguchi, Atsushi', 'Koshiba, Takumi', 'Nagata, Kyosuke', 'Takeyama, Haruko', 'Hasegawa, Hideki', 'Ichinohe, Takeshi']",,,,
,PMC,Suppression of Type I Interferon Production by Human T-Cell Leukemia Virus Type 1 Oncoprotein Tax through Inhibition of IRF3 Phosphorylation,http://dx.doi.org/10.1128/JVI.00129-16,PMC4810532,,,"Infection with human T-cell leukemia virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and tropical spastic paraparesis. Type I interferons (IFNs) are key effectors of the innate antiviral response, and IFN-α combined with the nucleoside reverse transcriptase inhibitor zidovudine is considered the standard first-line therapy for ATL. HTLV-1 oncoprotein Tax is known to suppress innate IFN production and response but the underlying mechanisms remain to be fully established. In this study, we report on the suppression of type I IFN production by HTLV-1 Tax through interaction with and inhibition of TBK1 kinase that phosphorylates IRF3. Induced transcription of IFN-β was severely impaired in HTLV-1-transformed ATL cells and freshly infected T lymphocytes. The ability to suppress IRF3 activation was ascribed to Tax. The expression of Tax alone sufficiently repressed the induction of IFN production by RIG-I plus PACT, cGAMP synthase plus STING, TBK1, IKKε, IRF3, and IRF7, but not by IRF3-5D, a dominant-active phosphomimetic mutant. This suggests that Tax perturbs IFN production at the step of IRF3 phosphorylation. Tax mutants deficient for CREB or NF-κB activation were fully competent in the suppression of IFN production. Coimmunoprecipitation experiments confirmed the association of Tax with TBK1, IKKε, STING, and IRF3. In vitro kinase assay indicated an inhibitory effect of Tax on TBK1-mediated phosphorylation of IRF3. Taken together, our findings suggested a new mechanism by which HTLV-1 oncoprotein Tax circumvents the production of type I IFNs in infected cells. Our findings have implications in therapeutic intervention of ATL. IMPORTANCE Human T-cell leukemia virus type 1 (HTLV-1) is the cause of adult T-cell leukemia (ATL), an aggressive and fatal blood cancer, as well as another chronic disabling disease of the spinal cord. Treatments are unsatisfactory, and options are limited. A combination of antiviral cellular protein alpha interferon and zidovudine, which is an inhibitor of a viral enzyme called reverse transcriptase, has been recommended as the standard first-line therapy for ATL. Exactly how HTLV-1 interacts with the cellular machinery for interferon production and action is not well understood. Our work sheds light on the mechanism of action for the inhibition of interferon production by an HTLV-1 oncogenic protein called Tax. Our findings might help to improve interferon-based anti-HTLV-1 and anti-ATL therapy.",,"['Yuen, Chun-Kit', 'Chan, Ching-Ping', 'Fung, Sin-Yee', 'Wang, Pei-Hui', 'Wong, Wan-Man', 'Tang, Hei-Man Vincent', 'Yuen, Kit-San', 'Chan, Chi-Ping', 'Jin, Dong-Yan', 'Kok, Kin-Hang']",,,,
,PMC,The Hemagglutinin Stem-Binding Monoclonal Antibody VIS410 Controls Influenza Virus-Induced Acute Respiratory Distress Syndrome,http://dx.doi.org/10.1128/AAC.02457-15,PMC4808199,,,"Most cases of severe influenza are associated with pulmonary complications, such as acute respiratory distress syndrome (ARDS), and no antiviral drugs of proven value for treating such complications are currently available. The use of monoclonal antibodies targeting the stem of the influenza virus surface hemagglutinin (HA) is a rapidly developing strategy for the control of viruses of multiple HA subtypes. However, the mechanisms of action of these antibodies are not fully understood, and their ability to mitigate severe complications of influenza has been poorly studied. We evaluated the effect of treatment with VIS410, a human monoclonal antibody targeting the HA stem region, on the development of ARDS in BALB/c mice after infection with influenza A(H7N9) viruses. Prophylactic administration of VIS410 resulted in the complete protection of mice against lethal A(H7N9) virus challenge. A single therapeutic dose of VIS410 given 24 h after virus inoculation resulted in dose-dependent protection of up to 100% of mice inoculated with neuraminidase inhibitor-susceptible or -resistant A(H7N9) viruses. Compared to the outcomes in mock-treated controls, a single administration of VIS410 improved viral clearance from the lungs, reduced virus spread in lungs in a dose-dependent manner, resulting in a lower lung injury score, reduced the extent of the alteration in lung vascular permeability and protein accumulation in bronchoalveolar lavage fluid, and improved lung physiologic function. Thus, antibodies targeting the HA stem can reduce the severity of ARDS and show promise as agents for controlling pulmonary complications in influenza.",,"['Baranovich, Tatiana', 'Jones, Jeremy C.', 'Russier, Marion', 'Vogel, Peter', 'Szretter, Kristy J.', 'Sloan, Susan E.', 'Seiler, Patrick', 'Trevejo, Jose M.', 'Webby, Richard J.', 'Govorkova, Elena A.']",,,,
,PMC,Novel Polyanions Inhibiting Replication of Influenza Viruses,http://dx.doi.org/10.1128/AAC.02183-15,PMC4808183,,,"Novel sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) and N-sulfonated chitosan (NSCH) have been synthesized, and their activity against influenza A and B viruses has been studied and compared with that of a series of carrageenans, marine polysaccharides of well-documented anti-influenza activity. NSPAHs were found to be nontoxic and very soluble in water, in contrast to gel-forming and thus generally poorly soluble carrageenans. In vitro and ex vivo studies using susceptible cells (Madin-Darby canine kidney epithelial cells and fully differentiated human airway epithelial cultures) demonstrated the antiviral effectiveness of NSPAHs. The activity of NSPAHs was proportional to the molecular mass of the chain and the degree of substitution of amino groups with sulfonate groups. Mechanistic studies showed that the NSPAHs and carrageenans inhibit influenza A and B virus assembly in the cell.",,"['Ciejka, Justyna', 'Milewska, Aleksandra', 'Wytrwal, Magdalena', 'Wojarski, Jacek', 'Golda, Anna', 'Ochman, Marek', 'Nowakowska, Maria', 'Szczubialka, Krzysztof', 'Pyrc, Krzysztof']",,,,
,PMC,"Comprehensive Screening for Naturally Occurring Hepatitis C Virus Resistance to Direct-Acting Antivirals in the NS3, NS5A, and NS5B Genes in Worldwide Isolates of Viral Genotypes 1 to 6",http://dx.doi.org/10.1128/AAC.02776-15,PMC4808155,,,"There is no comprehensive study available on the natural hepatitis C virus (HCV) polymorphism in sites associated with resistance including all viral genotypes which may present variable susceptibilities to particular direct-acting antivirals (DAAs). This study aimed to analyze the frequencies, genetic barriers, and evolutionary histories of naturally occurring resistance-associated variants (RAVs) in the six main HCV genotypes. A comprehensive analysis of up to 103 RAVs was performed in 2,901, 2,216, and 1,344 HCV isolates for the NS3, NS5A, and NS5B genes, respectively. We report significant intergenotypic differences in the frequencies of natural RAVs for these three HCV genes. In addition, we found a low genetic barrier for the generation of new RAVs, irrespective of the viral genotype. Furthermore, in 1,126 HCV genomes, including sequences spanning the three genes, haplotype analysis revealed a remarkably high frequency of viruses carrying more than one natural RAV to DAAs (53% of HCV-1a, 28.5% of HCV-1b, 67.1% of HCV-6, and 100% of genotype 2, 3, 4, and 5 haplotypes). With the exception of HCV-1a, the most prevalent haplotypes showed RAVs in at least two different viral genes. Finally, evolutionary analyses revealed that, while most natural RAVs appeared recently, others have been efficiently transmitted over time and cluster in well-supported clades. In summary, and despite the observed high efficacy of DAA-based regimens, we show that naturally occurring RAVs are common in all HCV genotypes and that there is an overall low genetic barrier for the selection of resistance mutations. There is a need for natural DAA resistance profiling specific for each HCV genotype.",,"['Patiño-Galindo, Juan Ángel', 'Salvatierra, Karina', 'González-Candelas, Fernando', 'López-Labrador, F. Xavier']",,,,
,PMC,Unbiased Detection of Respiratory Viruses by Use of RNA Sequencing-Based Metagenomics: a Systematic Comparison to a Commercial PCR Panel,http://dx.doi.org/10.1128/JCM.03060-15,PMC4809917,,,"Current infectious disease molecular tests are largely pathogen specific, requiring test selection based on the patient's symptoms. For many syndromes caused by a large number of viral, bacterial, or fungal pathogens, such as respiratory tract infections, this necessitates large panels of tests and has limited yield. In contrast, next-generation sequencing-based metagenomics can be used for unbiased detection of any expected or unexpected pathogen. However, barriers for its diagnostic implementation include incomplete understanding of analytical performance and complexity of sequence data analysis. We compared detection of known respiratory virus-positive (n = 42) and unselected (n = 67) pediatric nasopharyngeal swabs using an RNA sequencing (RNA-seq)-based metagenomics approach and Taxonomer, an ultrarapid, interactive, web-based metagenomics data analysis tool, with an FDA-cleared respiratory virus panel (RVP; GenMark eSensor). Untargeted metagenomics detected 86% of known respiratory virus infections, and additional PCR testing confirmed RVP results for only 2 (33%) of the discordant samples. In unselected samples, untargeted metagenomics had excellent agreement with the RVP (93%). In addition, untargeted metagenomics detected an additional 12 viruses that were either not targeted by the RVP or missed due to highly divergent genome sequences. Normalized viral read counts for untargeted metagenomics correlated with viral burden determined by quantitative PCR and showed high intrarun and interrun reproducibility. Partial or full-length viral genome sequences were generated in 86% of RNA-seq-positive samples, allowing assessment of antiviral resistance, strain-level typing, and phylogenetic relatedness. Overall, untargeted metagenomics had high agreement with a sensitive RVP, detected viruses not targeted by the RVP, and yielded epidemiologically and clinically valuable sequence information.",,"['Graf, Erin H.', 'Simmon, Keith E.', 'Tardif, Keith D.', 'Hymas, Weston', 'Flygare, Steven', 'Eilbeck, Karen', 'Yandell, Mark', 'Schlaberg, Robert']",,,,
,PMC,Tissue-Resident T Cells as the Central Paradigm of Chlamydia Immunity,http://dx.doi.org/10.1128/IAI.01378-15,PMC4807466,,,"For almost 2 decades, results from Chlamydia pathogenesis investigations have been conceptualized using a cytokine polarization narrative. Recent viral immunity studies identifying protective tissue-resident memory T cells (Trm) suggest an alternative paradigm based on localized immune networks. As Chlamydia vaccines enter the preclinical pipeline and, in the case of an attenuated trachoma vaccine, are given to human subjects, it may be useful to ask whether cytokine polarization is the appropriate framework for understanding and evaluating vaccine efficacy. In this review, we revisit C. trachomatis pathogenesis data from mice and humans using a Trm narrative and note a comfortable concordance with the Chlamydia pathogenesis literature.",,"['Johnson, Raymond M.', 'Brunham, Robert C.']",,,,
,PMC,Innate cell communication kick-starts pathogen-specific immunity,http://dx.doi.org/10.1038/ni.3375,PMC4949486,,,"Innate cells are responsible for the rapid recognition of infection and mediate essential mechanisms of pathogen elimination, and also facilitate adaptive immune responses. We review here the numerous intricate interactions among innate cells that initiate protective immunity. The efficient eradication of pathogens depends on the coordinated actions of multiple cells, including innate cells and epithelial cells. Rather than acting as isolated effector cells, innate cells are in constant communication with other responding cells of the immune system, locally and distally. These interactions are critically important for the efficient control of primary infections as well for the development of ‘trained’ innate cells that facilitate the rapid elimination of homologous or heterologous infections.",,"['Rivera, Amariliz', 'Siracusa, Mark C.', 'Yap, George S.', 'Gause, William C.']",,,,
,PMC,Leptin Resistance Contributes to Obesity in Mice with Null Mutation of Carcinoembryonic Antigen-related Cell Adhesion Molecule 1,http://dx.doi.org/10.1074/jbc.M116.716431,PMC4900262,,,"Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes hepatic insulin clearance. Consistently, mice with null mutation of Ceacam1 (Cc1(−/−)) exhibit impaired insulin clearance with increased lipid production in liver and redistribution to white adipose tissue, leading to visceral obesity at 2 months of age. When the mutation is propagated on the C57/BL6J genetic background, total fat mass rises significantly with age, and glucose intolerance and systemic insulin resistance develop at 6 months of age. This study was carried out to determine the mechanisms underlying the marked increase in total fat mass in 6-month-old mutants. Indirect calorimetry analysis showed that Cc1(−/−) mice develop hyperphagia and a significant reduction in physical activity, in particular in the early hours of the dark cycle, during which energy expenditure is only slightly lower than in wild-type mice. They also exhibit increased triglyceride accumulation in skeletal muscle, due in part to incomplete fatty acid β-oxidation. Mechanistically, hypothalamic leptin signaling is reduced, as demonstrated by blunted STAT3 phosphorylation in coronal sections in response to an intracerebral ventricular injection of leptin. Hypothalamic fatty-acid synthase activity is also elevated in the mutants. Together, the data show that the increase in total fat mass in Cc1(−/−) mice is mainly attributed to hyperphagia and reduced spontaneous physical activity. Although the contribution of the loss of CEACAM1 from anorexigenic proopiomelanocortin neurons in the arcuate nucleus is unclear, leptin resistance and elevated hypothalamic fatty-acid synthase activity could underlie altered energy balance in these mice.",,"['Heinrich, Garrett', 'Russo, Lucia', 'Castaneda, Tamara R.', 'Pfeiffer, Verena', 'Ghadieh, Hilda E.', 'Ghanem, Simona S.', 'Wu, Jieshen', 'Faulkner, Latrice D.', 'Ergün, Süleyman', 'McInerney, Marcia F.', 'Hill, Jennifer W.', 'Najjar, Sonia M.']",,,,
,PMC,Rapid and Long-Term Immunity Elicited by DNA-Encoded Antibody Prophylaxis and DNA Vaccination Against Chikungunya Virus,http://dx.doi.org/10.1093/infdis/jiw111,PMC4936642,,,"Background. Vaccination and passive antibody therapies are critical for controlling infectious diseases. Passive antibody administration has limitations, including the necessity for purification and multiple injections for efficacy. Vaccination is associated with a lag phase before generation of immunity. Novel approaches reported here utilize the benefits of both methods for the rapid generation of effective immunity. Methods. A novel antibody-based prophylaxis/therapy entailing the electroporation-mediated delivery of synthetic DNA plasmids encoding biologically active anti–chikungunya virus (CHIKV) envelope monoclonal antibody (dMAb) was designed and evaluated for antiviral efficacy, as well as for the ability to overcome shortcomings inherent with conventional active vaccination and passive immunotherapy. Results. One intramuscular injection of dMAb produced antibodies in vivo more rapidly than active vaccination with an anti-CHIKV DNA vaccine. This dMAb neutralized diverse CHIKV clinical isolates and protected mice from viral challenge. Combination of dMAb and the CHIKV DNA vaccine afforded rapid and long-lived protection. Conclusions. A DNA-based dMAb strategy induced rapid protection against an emerging viral infection. This method can be combined with DNA vaccination as a novel strategy to provide both short- and long-term protection against this emerging infectious disease. These studies have implications for pathogen treatment and control strategies.",,"['Muthumani, Karuppiah', 'Block, Peter', 'Flingai, Seleeke', 'Muruganantham, Nagarajan', 'Chaaithanya, Itta Krishna', 'Tingey, Colleen', 'Wise, Megan', 'Reuschel, Emma L.', 'Chung, Christopher', 'Muthumani, Abirami', 'Sarangan, Gopalsamy', 'Srikanth, Padma', 'Khan, Amir S.', 'Vijayachari, Paluru', 'Sardesai, Niranjan Y.', 'Kim, J. Joseph', 'Ugen, Kenneth E.', 'Weiner, David B.']",,,,
,PMC,Virological factors that increase the transmissibility of emerging human viruses,http://dx.doi.org/10.1073/pnas.1521582113,PMC4839412,,,"The early detection of pathogens with epidemic potential is of major importance to public health. Most emerging infections result in dead-end “spillover” events in which a pathogen is transmitted from an animal reservoir to a human but is unable to achieve the sustained human-to-human transmission necessary for a full-blown epidemic. It is therefore critical to determine why only some virus infections are efficiently transmitted among humans whereas others are not. We sought to determine which biological features best characterized those viruses that have achieved sustained human transmission. Accordingly, we compiled a database of 203 RNA and DNA human viruses and used an information theoretic approach to assess which of a set of key biological variables were the best predictors of human-to-human transmission. The variables analyzed were as follows: taxonomic classification; genome length, type, and segmentation; the presence or absence of an outer envelope; recombination frequency; duration of infection; host mortality; and whether or not a virus exhibits vector-borne transmission. This comparative analysis revealed multiple strong associations. In particular, we determined that viruses with low host mortality, that establish long-term chronic infections, and that are nonsegmented, nonenveloped, and, most importantly, not transmitted by vectors were more likely to be transmissible among humans. In contrast, variables including genome length, genome type, and recombination frequency had little predictive power. In sum, we have identified multiple biological features that seemingly determine the likelihood of interhuman viral transmissibility, in turn enabling general predictions of whether viruses of a particular type will successfully emerge in human populations.",,"['Geoghegan, Jemma L.', 'Senior, Alistair M.', 'Di Giallonardo, Francesca', 'Holmes, Edward C.']",,,,
,PMC,"Human, Pig, and Mouse Interferon-Induced Transmembrane Proteins Partially Restrict Pseudotyped Lentiviral Vectors",http://dx.doi.org/10.1089/hum.2015.156,PMC4840922,,,"Lentiviral vectors are increasingly used in clinical trials to treat genetic diseases. Our research has focused on strategies to improve lentiviral gene transfer efficiency in the airways. Previously we demonstrated that a feline immunodeficiency virus (FIV)-based lentiviral vector pseudotyped with the baculovirus envelope glycoprotein GP64 (GP64-FIV) efficiently transduced mouse nasal epithelia in vivo but transduced mouse intrapulmonary airways with 10-fold less efficiency. Here, we demonstrate that members of a family of proteins with antiviral activity, interferon-induced transmembrane proteins (IFITMs), are more highly expressed in mouse intrapulmonary airways as compared with mouse nasal airways. Using GP64- and VSV-G (vesicular stomatitis virus G glycoprotein)-pseudotyped FIV, we show that expression of mouse IFITM1, IFITM2, and IFITM3 restricts gene transfer. Further, we show that both the nasal and intrapulmonary airways of IFITM locus knockout mice are more efficiently transduced with GP64-FIV than their heterozygous littermates. In anticipation of transitioning our studies into pig models of airway disease and clinical trials in humans, we investigated the ability of pig and human IFITMs to restrict lentiviral gene transfer. We observed that both human and pig IFITMs partially restricted both VSV-G-FIV and GP64-FIV transduction in vitro. Previous studies have focused on IFITM-mediated restriction of replication-competent wild-type viruses; however, these results implicate the IFITM proteins as restriction factors that can limit lentivirus-based vector gene transfer to airway epithelia. The findings are relevant to future preclinical and clinical airway gene therapy trials using lentivirus-based vectors.",,"['Hornick, Andrew L.', 'Li, Ni', 'Oakland, Mayumi', 'McCray, Paul B.', 'Sinn, Patrick L.']",,,,
,PMC,Design and Construction of Chimeric VP8-S2 Antigen for Bovine Rotavirus and Bovine Coronavirus,http://dx.doi.org/10.15171/apb.2016.014,PMC4845540,,,"Purpose: Bovine Rotavirus and Bovine Coronavirus are the most important causes of diarrhea in newborn calves and in some other species such as pigs and sheep. Rotavirus VP8 subunit is the major determinant of the viral infectivity and neutralization. Spike glycoprotein of coronavirus is responsible for induction of neutralizing antibody response. Methods: In the present study, several prediction programs were used to predict B and T-cells epitopes, secondary and tertiary structures, antigenicity ability and enzymatic degradation sites. Finally, a chimeric antigen was designed using computational techniques. The chimeric VP8-S2 antigen was constructed. It was cloned and sub-cloned into pGH and pET32a(+) expression vector. The recombinant pET32a(+)-VP8-S2 vector was transferred into E.oli BL21CodonPlus (DE3) as expression host. The recombinant VP8-S2 protein was purified by Ni-NTA chromatography column. Results: The results of colony PCR, enzyme digestion and sequencing showed that the VP8-S2 chimeric antigen has been successfully cloned and sub-cloned into pGH and pET32a(+).The results showed that E.coli was able to express VP8-S2 protein appropriately. This protein was expressed by induction of IPTG at concentration of 1mM and it was confirmed by Ni–NTA column, dot-blotting analysis and SDS-PAGE electrophoresis. Conclusion: The results of this study showed that E.coli can be used as an appropriate host to produce the recombinant VP8-S2 protein. This recombinant protein may be suitable to investigate to produce immunoglobulin, recombinant vaccine and diagnostic kit in future studies after it passes biological activity tests in vivo in animal model and or other suitable procedure.",,"['Nasiri, Khadijeh', 'Nassiri, Mohammadreza', 'Tahmoorespur, Mojtaba', 'Haghparast, Alireza', 'Zibaee, Saeed']",,,,
,PMC,Docking Screens for Novel Ligands Conferring New Biology,http://dx.doi.org/10.1021/acs.jmedchem.5b02008,PMC4865415,,,"It is now plausible to dock libraries of 10 million molecules against targets over several days or weeks. When the molecules screened are commercially available, they may be rapidly tested to find new leads. Although docking retains important liabilities (it cannot calculate affinities accurately nor even reliably rank order high-scoring molecules), it can often can distinguish likely from unlikely ligands, often with hit rates above 10%. Here we summarize the improvements in libraries, target quality, and methods that have supported these advances, and the open access resources that make docking accessible. Recent docking screens for new ligands are sketched, as are the binding, crystallographic, and in vivo assays that support them. Like any technique, controls are crucial, and key experimental ones are reviewed. With such controls, docking campaigns can find ligands with new chemotypes, often revealing the new biology that may be docking’s greatest impact over the next few years.",,"['Irwin, John J.', 'Shoichet, Brian K.']",,,,
,PMC,In This Issue,http://dx.doi.org/10.1073/iti1116113,PMC4801237,,,,,,,,,
,PMC,Global Health Security After Ebola: Four Global Commissions,http://dx.doi.org/10.1111/1468-0009.12176,PMC4941965,,,,,"GOSTIN, LAWRENCE O.",,,,
,PMC,Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo,http://dx.doi.org/10.1073/pnas.1601911113,PMC4822574,,,"Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium’s protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.",,"['Chan, Michael C. W.', 'Kuok, Denise I. T.', 'Leung, Connie Y. H.', 'Hui, Kenrie P. Y.', 'Valkenburg, Sophie A.', 'Lau, Eric H. Y.', 'Nicholls, John M.', 'Fang, Xiaohui', 'Guan, Yi', 'Lee, Jae W.', 'Chan, Renee W. Y.', 'Webster, Robert G.', 'Matthay, Michael A.', 'Peiris, J. S. Malik']",,,,
,PMC,Moving beyond metagenomics to find the next pandemic virus,http://dx.doi.org/10.1073/pnas.1601512113,PMC4801287,,,,,"Racaniello, Vincent",,,,
,PMC,SARS-like WIV1-CoV poised for human emergence,http://dx.doi.org/10.1073/pnas.1517719113,PMC4801244,,,"Outbreaks from zoonotic sources represent a threat to both human disease as well as the global economy. Despite a wealth of metagenomics studies, methods to leverage these datasets to identify future threats are underdeveloped. In this study, we describe an approach that combines existing metagenomics data with reverse genetics to engineer reagents to evaluate emergence and pathogenic potential of circulating zoonotic viruses. Focusing on the severe acute respiratory syndrome (SARS)-like viruses, the results indicate that the WIV1-coronavirus (CoV) cluster has the ability to directly infect and may undergo limited transmission in human populations. However, in vivo attenuation suggests additional adaptation is required for epidemic disease. Importantly, available SARS monoclonal antibodies offered success in limiting viral infection absent from available vaccine approaches. Together, the data highlight the utility of a platform to identify and prioritize prepandemic strains harbored in animal reservoirs and document the threat posed by WIV1-CoV for emergence in human populations.",,"['Menachery, Vineet D.', 'Yount, Boyd L.', 'Sims, Amy C.', 'Debbink, Kari', 'Agnihothram, Sudhakar S.', 'Gralinski, Lisa E.', 'Graham, Rachel L.', 'Scobey, Trevor', 'Plante, Jessica A.', 'Royal, Scott R.', 'Swanstrom, Jesica', 'Sheahan, Timothy P.', 'Pickles, Raymond J.', 'Corti, Davide', 'Randell, Scott H.', 'Lanzavecchia, Antonio', 'Marasco, Wayne A.', 'Baric, Ralph S.']",,,,
,PMC,A Recombinant Adenovirus Expressing Ovine Interferon Tau Prevents Influenza Virus-Induced Lethality in Mice,http://dx.doi.org/10.1128/JVI.03258-15,PMC4794696,,,"Ovine interferon tau (IFN-τ) is a unique type I interferon with low toxicity and a broad host range in vivo. We report the generation of a nonreplicative recombinant adenovirus expressing biologically active IFN-τ. Using the B6.A2G-Mx1 mouse model, we showed that single-dose intranasal administration of recombinant Ad5-IFN-τ can effectively prevent lethality and disease induced by highly virulent hv-PR8 influenza virus by activating the interferon response and preventing viral replication.",,"['Martín, V.', 'Pascual, E.', 'Avia, M.', 'Rangel, G.', 'de Molina, A.', 'Alejo, A.', 'Sevilla, N.']",,,,
,PMC,Role of Mitochondrial Membrane Spherules in Flock House Virus Replication,http://dx.doi.org/10.1128/JVI.03080-15,PMC4794695,,,"Viruses that generate double-stranded RNA (dsRNA) during replication must overcome host defense systems designed to detect this infection intermediate. All positive-sense RNA viruses studied to date modify host membranes to help facilitate the sequestration of dsRNA from host defenses and concentrate replication factors to enhance RNA production. Flock House virus (FHV) is an attractive model for the study of these processes since it is well characterized and infects Drosophila cells, which are known to have a highly effective RNA silencing system. During infection, FHV modifies the outer membrane of host mitochondria to form numerous membrane invaginations, called spherules, that are ∼50 nm in diameter and known to be the site of viral RNA replication. While previous studies have outlined basic structural features of these invaginations, very little is known about the mechanism underlying their formation. Here we describe the optimization of an experimental system for the analysis of FHV host membrane modifications using crude mitochondrial preparations from infected Drosophila cells. These preparations can be programmed to synthesize both single- and double-stranded FHV RNA. The system was used to demonstrate that dsRNA is protected from nuclease digestion by virus-induced membrane invaginations and that spherules play an important role in stimulating RNA replication. Finally, we show that spherules generated during FHV infection appear to be dynamic as evidenced by their ability to form or disperse based on the presence or absence of RNA synthesis. IMPORTANCE It is well established that positive-sense RNA viruses induce significant membrane rearrangements in infected cells. However, the molecular mechanisms underlying these rearrangements, particularly membrane invagination and spherule formation, remain essentially unknown. How the formation of spherules enhances viral RNA synthesis is also not understood, although it is assumed to be partly a result of evading host defense pathways. To help interrogate some of these issues, we optimized a cell-free replication system consisting of mitochondria isolated from Flock House virus-infected Drosophila cells for use in biochemical and structural studies. Our data suggest that spherules generated during Flock House virus replication are dynamic, protect double-stranded RNA, and enhance RNA replication in general. Cryo-electron microscopy suggests that the samples are amenable to detailed structural analyses of spherules engaged in RNA synthesis. This system thus provides a foundation for understanding the molecular mechanisms underlying spherule formation, maintenance, and function during positive-sense viral RNA replication.",,"['Short, James R.', 'Speir, Jeffrey A.', 'Gopal, Radhika', 'Pankratz, Logan M.', 'Lanman, Jason', 'Schneemann, Anette']",,,,
,PMC,"Morphological, Biochemical, and Functional Study of Viral Replication Compartments Isolated from Adenovirus-Infected Cells",http://dx.doi.org/10.1128/JVI.00033-16,PMC4794690,,,"Adenovirus (Ad) replication compartments (RC) are nuclear microenvironments where the viral genome is replicated and a coordinated program of late gene expression is established. These virus-induced nuclear sites seem to behave as central hubs for the regulation of virus-host cell interactions, since proteins that promote efficient viral replication as well as factors that participate in the antiviral response are coopted and concentrated there. To gain further insight into the activities of viral RC, here we report, for the first time, the morphology, composition, and activities of RC isolated from Ad-infected cells. Morphological analyses of isolated RC particles by superresolution microscopy showed that they were indistinguishable from RC within infected cells and that they displayed a dynamic compartmentalization. Furthermore, the RC-containing fractions (RCf) proved to be functional, as they directed de novo synthesis of viral DNA and RNA as well as RNA splicing, activities that are associated with RC in vivo. A detailed analysis of the production of viral late mRNA from RCf at different times postinfection revealed that viral mRNA splicing occurs in RC and that the synthesis, posttranscriptional processing, and release from RC to the nucleoplasm of individual viral late transcripts are spatiotemporally separate events. The results presented here demonstrate that RCf are a powerful system for detailed study into RC structure, composition, and activities and, as a result, the determination of the molecular mechanisms that induce the formation of these viral sites of adenoviruses and other nuclear-replicating viruses. IMPORTANCE RC may represent molecular hubs where many aspects of virus-host cell interaction are controlled. Here, we show by superresolution microscopy that RCf have morphologies similar to those of RC within Ad-infected cells and that they appear to be compartmentalized, as nucleolin and DBP display different localization in the periphery of these viral sites. RCf proved to be functional, as they direct de novo synthesis of viral DNA and mRNA, allowing the detailed study of the regulation of viral genome replication and expression. Furthermore, we show that the synthesis and splicing of individual viral late mRNA occurs in RC and that they are subject to different temporal patterns of regulation, from their synthesis to their splicing and release from RC to the nucleoplasm. Hence, RCf represent a novel system to study molecular mechanisms that are orchestrated in viral RC to take control of the infected cell and promote an efficient viral replication cycle.",,"['Hidalgo, Paloma', 'Anzures, Lourdes', 'Hernández-Mendoza, Armando', 'Guerrero, Adán', 'Wood, Christopher D.', 'Valdés, Margarita', 'Dobner, Thomas', 'Gonzalez, Ramón A.']",,,,
,PMC,Equine Arteritis Virus Uses Equine CXCL16 as an Entry Receptor,http://dx.doi.org/10.1128/JVI.02455-15,PMC4794689,,,"Previous studies in our laboratory have identified equine CXCL16 (EqCXCL16) to be a candidate molecule and possible cell entry receptor for equine arteritis virus (EAV). In horses, the CXCL16 gene is located on equine chromosome 11 (ECA11) and encodes a glycosylated, type I transmembrane protein with 247 amino acids. Stable transfection of HEK-293T cells with plasmid DNA carrying EqCXCL16 (HEK-EqCXCL16 cells) increased the proportion of the cell population permissive to EAV infection from <3% to almost 100%. The increase in permissiveness was blocked either by transfection of HEK-EqCXCL16 cells with small interfering RNAs (siRNAs) directed against EqCXCL16 or by pretreatment with guinea pig polyclonal antibody against EqCXCL16 protein (Gp anti-EqCXCL16 pAb). Furthermore, using a virus overlay protein-binding assay (VOPBA) in combination with far-Western blotting, gradient-purified EAV particles were shown to bind directly to the EqCXCL16 protein in vitro. The binding of biotinylated virulent EAV strain Bucyrus at 4°C was significantly higher in HEK-EqCXCL16 cells than nontransfected HEK-293T cells. Finally, the results demonstrated that EAV preferentially infects subpopulations of horse CD14(+) monocytes expressing EqCXCL16 and that infection of these cells is significantly reduced by pretreatment with Gp anti-EqCXCL16 pAb. The collective data from this study provide confirmatory evidence that the transmembrane form of EqCXCL16 likely plays a major role in EAV host cell entry processes, possibly acting as a primary receptor molecule for this virus. IMPORTANCE Outbreaks of EVA can be a source of significant economic loss for the equine industry from high rates of abortion in pregnant mares, death in young foals, establishment of the carrier state in stallions, and trade restrictions imposed by various countries. Similar to other arteriviruses, EAV primarily targets cells of the monocyte/macrophage lineage, which, when infected, are believed to play a critical role in EVA pathogenesis. To this point, however, the host-specified molecules involved in EAV binding and entry into monocytes/macrophages have not been identified. Identification of the cellular receptors for EAV may provide insights to design antivirals and better prophylactic reagents. In this study, we have demonstrated that EqCXCL16 acts as an EAV entry receptor in EAV-susceptible cells, equine monocytes. These findings represent a significant advance in our understanding of the fundamental mechanisms associated with the entry of EAV into susceptible cells.",,"['Sarkar, Sanjay', 'Chelvarajan, Lakshman', 'Go, Yun Young', 'Cook, Frank', 'Artiushin, Sergey', 'Mondal, Shankar', 'Anderson, Kelsi', 'Eberth, John', 'Timoney, Peter J.', 'Kalbfleisch, Theodore S.', 'Bailey, Ernest', 'Balasuriya, Udeni B. R.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00205-16,PMC4794688,,,,,,,,,
,PMC,ISG15 Is Upregulated in Respiratory Syncytial Virus Infection and Reduces Virus Growth through Protein ISGylation,http://dx.doi.org/10.1128/JVI.02695-15,PMC4794669,,,"Human respiratory syncytial virus (RSV), for which neither a vaccine nor an effective therapeutic treatment is currently available, is the leading cause of severe lower respiratory tract infections in children. Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein that is highly increased during viral infections and has been reported to have an antiviral or a proviral activity, depending on the virus. Previous studies from our laboratory demonstrated strong ISG15 upregulation during RSV infection in vitro. In this study, an in-depth analysis of the role of ISG15 in RSV infection is presented. ISG15 overexpression and small interfering RNA (siRNA)-silencing experiments, along with ISG15 knockout (ISG15(−/−)) cells, revealed an anti-RSV effect of the molecule. Conjugation inhibition assays demonstrated that ISG15 exerts its antiviral activity via protein ISGylation. This antiviral activity requires high levels of ISG15 to be present in the cells before RSV infection. Finally, ISG15 is also upregulated in human respiratory pseudostratified epithelia and in nasopharyngeal washes from infants infected with RSV, pointing to a possible antiviral role of the molecule in vivo. These results advance our understanding of the innate immune response elicited by RSV and open new possibilities to control infections by the virus. IMPORTANCE At present, no vaccine or effective treatment for human respiratory syncytial virus (RSV) is available. This study shows that interferon-stimulated gene 15 (ISG15) lowers RSV growth through protein ISGylation. In addition, ISG15 accumulation highly correlates with the RSV load in nasopharyngeal washes from children, indicating that ISG15 may also have an antiviral role in vivo. These results improve our understanding of the innate immune response to RSV and identify ISG15 as a potential target for virus control.",,"['González-Sanz, Rubén', 'Mata, Manuel', 'Bermejo-Martín, Jesús', 'Álvarez, Amparo', 'Cortijo, Julio', 'Melero, José A.', 'Martínez, Isidoro']",,,,
,PMC,Extensive Positive Selection Drives the Evolution of Nonstructural Proteins in Lineage C Betacoronaviruses,http://dx.doi.org/10.1128/JVI.02988-15,PMC4794664,,,"Middle East respiratory syndrome-related coronavirus (MERS-CoV) spreads to humans via zoonotic transmission from camels. MERS-CoV belongs to lineage C of betacoronaviruses (betaCoVs), which also includes viruses isolated from bats and hedgehogs. A large portion of the betaCoV genome consists of two open reading frames (ORF1a and ORF1b) that are translated into polyproteins. These are cleaved by viral proteases to generate 16 nonstructural proteins (nsp1 to nsp16) which compose the viral replication-transcription complex. We investigated the evolution of ORF1a and ORF1b in lineage C betaCoVs. Results indicated widespread positive selection, acting mostly on ORF1a. The proportion of positively selected sites in ORF1a was much higher than that previously reported for the surface-exposed spike protein. Selected sites were unevenly distributed, with nsp3 representing the preferential target. Several pairs of coevolving sites were also detected, possibly indicating epistatic interactions; most of these were located in nsp3. Adaptive evolution at nsp3 is ongoing in MERS-CoV strains, and two selected sites (G720 and R911) were detected in the protease domain. While position 720 is variable in camel-derived viruses, suggesting that the selective event does not represent a specific adaptation to humans, the R911C substitution was observed only in human-derived MERS-CoV isolates, including the viral strain responsible for the recent South Korean outbreak. It will be extremely important to assess whether these changes affect host range or other viral phenotypes. More generally, data herein indicate that CoV nsp3 represents a major selection target and that nsp3 sequencing should be envisaged in monitoring programs and field surveys. IMPORTANCE Both severe acute respiratory syndrome coronavirus (SARS-CoV) and MERS-CoV originated in bats and spread to humans via an intermediate host. This clearly highlights the potential for coronavirus host shifting and the relevance of understanding the molecular events underlying the adaptation to new host species. We investigated the evolution of ORF1a and ORF1b in lineage C betaCoVs and in 87 sequenced MERS-CoV isolates. Results indicated widespread positive selection, stronger in ORF1a than in ORF1b. Several selected sites were found to be located in functionally relevant protein regions, and some of them corresponded to functional mutations in other coronaviruses. The proportion of selected sites we identified in ORF1a is much higher than that for the surface-exposed spike protein. This observation suggests that adaptive evolution in ORF1a might contribute to host shifts or immune evasion. Data herein also indicate that genetic diversity at nonstructural proteins should be taken into account when antiviral compounds are developed.",,"['Forni, Diego', 'Cagliani, Rachele', 'Mozzi, Alessandra', 'Pozzoli, Uberto', 'Al-Daghri, Nasser', 'Clerici, Mario', 'Sironi, Manuela']",,,,
,PMC,Glycoprotein-Specific Antibodies Produced by DNA Vaccination Protect Guinea Pigs from Lethal Argentine and Venezuelan Hemorrhagic Fever,http://dx.doi.org/10.1128/JVI.02969-15,PMC4794662,,,"Several members of the Arenaviridae can cause acute febrile diseases in humans, often resulting in lethality. The use of convalescent-phase human plasma is an effective treatment in humans infected with arenaviruses, particularly species found in South America. Despite this, little work has focused on developing potent and defined immunotherapeutics against arenaviruses. In the present study, we produced arenavirus neutralizing antibodies by DNA vaccination of rabbits with plasmids encoding the full-length glycoprotein precursors of Junín virus (JUNV), Machupo virus (MACV), and Guanarito virus (GTOV). Geometric mean neutralizing antibody titers, as measured by the 50% plaque reduction neutralization test (PRNT(50)), exceeded 5,000 against homologous viruses. Antisera against each targeted virus exhibited limited cross-species binding and, to a lesser extent, cross-neutralization. Anti-JUNV glycoprotein rabbit antiserum protected Hartley guinea pigs from lethal intraperitoneal infection with JUNV strain Romero when the antiserum was administered 2 days after challenge and provided some protection (∼30%) when administered 4 days after challenge. Treatment starting on day 6 did not protect animals. We further formulated an IgG antibody cocktail by combining anti-JUNV, -MACV, and -GTOV antibodies produced in DNA-vaccinated rabbits. This cocktail protected 100% of guinea pigs against JUNV and GTOV lethal disease. We then expanded on this cocktail approach by simultaneously vaccinating rabbits with a combination of plasmids encoding glycoproteins from JUNV, MACV, GTOV, and Sabia virus (SABV). Sera collected from rabbits vaccinated with the combination vaccine neutralized all four targets. These findings support the concept of using a DNA vaccine approach to generate a potent pan-arenavirus immunotherapeutic. IMPORTANCE Arenaviruses are an important family of emerging viruses. In infected humans, convalescent-phase plasma containing neutralizing antibodies can mitigate the severity of disease caused by arenaviruses, particularly species found in South America. Because of variations in potency of the human-derived product, limited availability, and safety concerns, this treatment option has essentially been abandoned. Accordingly, despite this approach being an effective postinfection treatment option, research on novel approaches to produce potent polyclonal antibody-based therapies have been deficient. Here we show that DNA-based vaccine technology can be used to make potently neutralizing antibodies in rabbits that exclusively target the glycoproteins of several human-pathogenic arenaviruses found in South America, including JUNV, MACV, GTOV, and SABV. These antibodies protected guinea pigs from lethal disease when given post-virus challenge. We also generated a purified antibody cocktail with antibodies targeting three arenaviruses and demonstrated protective efficacy against all three targets. Our findings demonstrate that use of the DNA vaccine technology could be used to produce candidate antiarenavirus neutralizing antibody-based products.",,"['Golden, Joseph W.', 'Maes, Piet', 'Kwilas, Steven A.', 'Ballantyne, John', 'Hooper, Jay W.']",,,,
,PMC,Mutations in a Highly Conserved Motif of nsp1β Protein Attenuate the Innate Immune Suppression Function of Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1128/JVI.03069-15,PMC4794661,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) nonstructural protein 1β (nsp1β) is a multifunctional viral protein, which is involved in suppressing the host innate immune response and activating a unique −2/−1 programmed ribosomal frameshifting (PRF) signal for the expression of frameshifting products. In this study, site-directed mutagenesis analysis showed that the R128A or R129A mutation introduced into a highly conserved motif ((123)GKYLQRRLQ(131)) reduced the ability of nsp1β to suppress interferon beta (IFN-β) activation and also impaired nsp1β's function as a PRF transactivator. Three recombinant viruses, vR128A, vR129A, and vRR129AA, carrying single or double mutations in the GKYLQRRLQ motif were characterized. In comparison to the wild-type (WT) virus, vR128A and vR129A showed slightly reduced growth abilities, while the vRR129AA mutant had a significantly reduced growth ability in infected cells. Consistent with the attenuated growth phenotype in vitro, pigs infected with nsp1β mutants had lower levels of viremia than did WT virus-infected pigs. Compared to the WT virus in infected cells, all three mutated viruses stimulated high levels of IFN-α expression and exhibited a reduced ability to suppress the mRNA expression of selected interferon-stimulated genes (ISGs). In pigs infected with nsp1β mutants, IFN-α production was increased in the lungs at early time points postinfection, which was correlated with increased innate NK cell function. Furthermore, the augmented innate response was consistent with the increased production of IFN-γ in pigs infected with mutated viruses. These data demonstrate that residues R128 and R129 are critical for nsp1β function and that modifying these key residues in the GKYLQRRLQ motif attenuates virus growth ability and improves the innate and adaptive immune responses in infected animals. IMPORTANCE PRRSV infection induces poor antiviral innate IFN and cytokine responses, which results in weak adaptive immunity. One of the strategies in next-generation vaccine construction is to manipulate viral proteins/genetic elements involved in antagonizing the host immune response. PRRSV nsp1β was identified to be a strong innate immune antagonist. In this study, two basic amino acids, R128 and R129, in a highly conserved GKYLQRRLQ motif were determined to be critical for nsp1β function. Mutations introduced into these two residues attenuated virus growth and improved the innate and adaptive immune responses of infected animals. Technologies developed in this study could be broadly applied to current commercial PRRSV modified live-virus (MLV) vaccines and other candidate vaccines.",,"['Li, Yanhua', 'Shyu, Duan-Liang', 'Shang, Pengcheng', 'Bai, Jianfa', 'Ouyang, Kang', 'Dhakal, Santosh', 'Hiremath, Jagadish', 'Binjawadagi, Basavaraj', 'Renukaradhya, Gourapura J.', 'Fang, Ying']",,,,
,PMC,"During Infection, Theiler's Virions Are Cleaved by Caspases and Disassembled into Pentamers",http://dx.doi.org/10.1128/JVI.03035-15,PMC4794658,,,"Infected macrophages in spinal cords of mice persistently infected with Theiler's murine encephalomyelitis virus (TMEV) undergo apoptosis, resulting in restricted virus yields, as do infected macrophages in culture. Apoptosis of murine macrophages in culture occurs via the intrinsic pathway later in infection (>10 h postinfection [p.i.]) after maximal virus titers (150 to 200 PFU/cell) have been reached, with loss of most infectious virus (<5 PFU/cell) by 20 to 24 h p.i. Here, we show that BeAn virus RNA replication, translation, polyprotein processing into final protein products, and assembly of protomers and pentamers in infected M1-D macrophages did not differ from those processes in TMEV-infected BHK-21 cells, which undergo necroptosis. However, the initial difference from BHK-21 cell infection was seen at 10 to 12 h p.i., where virions from the 160S peak in sucrose gradients had incompletely processed VP0 (compared to that in infected BHK-21 cells). Thereafter, there was a gradual loss of the 160S virion peak in sucrose gradients, with replacement by a 216S peak that was observed to contain pentamers among lipid debris in negatively stained grids by electron microscopy. After infection or incubation of purified virions with activated caspase-3 in vitro, 13- and 17-kDa capsid peptide fragments were observed and were predicted by algorithms to contain cleavage sites within proteins by cysteine-dependent aspartate-directed proteases. These findings suggest that caspase cleavage of sites in exposed capsid loops of assembled virions occurs contemporaneously with the onset and progression of apoptosis later in the infection. IMPORTANCE Theiler's murine encephalomyelitis virus (TMEV) infection in mice results in establishment of virus persistence in the central nervous system and chronic inflammatory demyelinating disease, providing an experimental animal model for multiple sclerosis. Virus persistence takes place primarily in macrophages recruited into the spinal cord that undergo apoptosis and in turn may facilitate viral spread via infected apoptotic blebs. Infection of murine macrophages in culture results in restricted virus yields late in infection. Here it is shown that the early steps of the virus life cycle in infected macrophages in vitro do not differ from these processes in TMEV-infected BHK-21 cells, which undergo necroptosis. However, the findings late in infection suggest that caspases cleave sites in exposed capsid loops and possibly internal sites of assembled virions occurring contemporaneously with onset and progression of apoptosis. Mechanistically, this would explain the dramatic loss in virus yields during TMEV-induced apoptosis and attenuate the virus, enabling persistence.",,"['Arslan, Sevim Yildiz', 'Son, Kyung-No', 'Lipton, Howard L.']",,,,
,PMC,Normalization of cardiac substrate utilization and left ventricular hypertrophy precede functional recovery in heart failure regression,http://dx.doi.org/10.1093/cvr/cvw051,PMC4836630,,,"AIMS: Impaired cardiac substrate metabolism plays an important role in heart failure (HF) pathogenesis. Since many of these metabolic changes occur at the transcriptional level of metabolic enzymes, it is possible that this loss of metabolic flexibility is permanent and thus contributes to worsening cardiac function and/or prevents the full regression of HF upon treatment. However, despite the importance of cardiac energetics in HF, it remains unclear whether these metabolic changes can be normalized. In the current study, we investigated whether a reversal of an elevated aortic afterload in mice with severe HF would result in the recovery of cardiac function, substrate metabolism, and transcriptional reprogramming as well as determined the temporal relationship of these changes. METHODS AND RESULTS: Male C57Bl/6 mice were subjected to either Sham or transverse aortic constriction (TAC) surgery to induce HF. After HF development, mice with severe HF (% ejection fraction <30) underwent a second surgery to remove the aortic constriction (debanding, DB). Three weeks following DB, there was a near complete recovery of systolic and diastolic function, and gene expression of several markers for hypertrophy/HF were returned to values observed in healthy controls. Interestingly, pressure-overload-induced left ventricular hypertrophy (LVH) and cardiac substrate metabolism were restored at 1-week post-DB, which preceded functional recovery. CONCLUSIONS: The regression of severe HF is associated with early and dramatic improvements in cardiac energy metabolism and LVH normalization that precede restored cardiac function, suggesting that metabolic and structural improvements may be critical determinants for functional recovery.",,"['Byrne, Nikole J.', 'Levasseur, Jody', 'Sung, Miranda M.', 'Masson, Grant', 'Boisvenue, Jamie', 'Young, Martin E.', 'Dyck, Jason R.B.']",,,,
,PMC,Humanized mouse G6 anti-idiotypic monoclonal antibody has therapeutic potential against IGHV1-69 germline gene-based B-CLL,http://dx.doi.org/10.1080/19420862.2016.1159365,PMC4966851,,,"In 10–20% of the cases of chronic lymphocytic leukemia of B-cell phenotype (B-CLL), the IGHV1-69 germline is utilized as VH gene of the B cell receptor (BCR). Mouse G6 (MuG6) is an anti-idiotypic monoclonal antibody discovered in a screen against rheumatoid factors (RFs) that binds with high affinity to an idiotope expressed on the 51p1 alleles of IGHV1-69 germline gene encoded antibodies (G6-id(+)). The finding that unmutated IGHV1-69 encoded BCRs are frequently expressed on B-CLL cells provides an opportunity for anti-idiotype monoclonal antibody immunotherapy. In this study, we first showed that MuG6 can deplete B cells encoding IGHV1-69 BCRs using a novel humanized GTL mouse model. Next, we humanized MuG6 and demonstrated that the humanized antibodies (HuG6s), especially HuG6.3, displayed ∼2-fold higher binding affinity for G6-id(+) antibody compared to the parental MuG6. Additional studies showed that HuG6.3 was able to kill G6-id(+) BCR expressing cells and patient B-CLL cells through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Finally, both MuG6 and HuG6.3 mediate in vivo depletion of B-CLL cells in NSG mice. These data suggest that HuG6.3 may provide a new precision medicine to selectively kill IGHV1-69-encoding G6-id(+) B-CLL cells.",,"['Chang, De-Kuan', 'Kurella, Vinodh B.', 'Biswas, Subhabrata', 'Avnir, Yuval', 'Sui, Jianhua', 'Wang, Xueqian', 'Sun, Jiusong', 'Wang, Yanyan', 'Panditrao, Madhura', 'Peterson, Eric', 'Tallarico, Aimee', 'Fernandes, Stacey', 'Goodall, Margaret', 'Zhu, Quan', 'Brown, Jennifer R.', 'Jefferis, Roy', 'Marasco, Wayne A']",,,,
,PMC,Occupational Hazards in the Thai Healthcare Sector,http://dx.doi.org/10.1177/1048291116633871,PMC5812467,,,"Healthcare personnel work in vulnerable conditions that can adversely impact physical and/or mental health. This paper aims to synthesize the state of knowledge on work-related illnesses, injuries, and risks experienced by Thai healthcare workers. We found that Thai healthcare personnel, like others worldwide, are at risk for injury related to needle sticks and sharp instruments; infectious diseases due to biological hazards exposure such as airborne pathogens and patient secretions; muscle pain due to workload and long duration of work; and psychological disorders related to stressful working conditions. Because detailed surveillance data are limited for the Thai healthcare workforce, we recommend that additional surveillance data on Thai healthcare workers’ health outcomes be collected. Future research efforts should also focus on evidence-based interventions in order to develop methods to prevent and treat occupational health injuries and illnesses acquired in the workplace for Thai healthcare sector workers.",,"['Tipayamongkholgul, Mathuros', 'Luksamijarulkul, Pipat', 'Mawn, Barbara', 'Kongtip, Pornpimol', 'Woskie, Susan']",,,,
,PMC,Effectiveness of N95 respirators versus surgical masks in protecting health care workers from acute respiratory infection: a systematic review and meta-analysis,http://dx.doi.org/10.1503/cmaj.150835,PMC4868605,,,"BACKGROUND: Conflicting recommendations exist related to which facial protection should be used by health care workers to prevent transmission of acute respiratory infections, including pandemic influenza. We performed a systematic review of both clinical and surrogate exposure data comparing N95 respirators and surgical masks for the prevention of transmissible acute respiratory infections. METHODS: We searched various electronic databases and the grey literature for relevant studies published from January 1990 to December 2014. Randomized controlled trials (RCTs), cohort studies and case–control studies that included data on health care workers wearing N95 respirators and surgical masks to prevent acute respiratory infections were included in the meta-analysis. Surrogate exposure studies comparing N95 respirators and surgical masks using manikins or adult volunteers under simulated conditions were summarized separately. Outcomes from clinical studies were laboratory-confirmed respiratory infection, influenza-like illness and workplace absenteeism. Outcomes from surrogate exposure studies were filter penetration, face-seal leakage and total inward leakage. RESULTS: We identified 6 clinical studies (3 RCTs, 1 cohort study and 2 case–control studies) and 23 surrogate exposure studies. In the meta-analysis of the clinical studies, we found no significant difference between N95 respirators and surgical masks in associated risk of (a) laboratory-confirmed respiratory infection (RCTs: odds ratio [OR] 0.89, 95% confidence interval [CI] 0.64–1.24; cohort study: OR 0.43, 95% CI 0.03–6.41; case–control studies: OR 0.91, 95% CI 0.25–3.36); (b) influenza-like illness (RCTs: OR 0.51, 95% CI 0.19–1.41); or (c) reported workplace absenteeism (RCT: OR 0.92, 95% CI 0.57–1.50). In the surrogate exposure studies, N95 respirators were associated with less filter penetration, less face-seal leakage and less total inward leakage under laboratory experimental conditions, compared with surgical masks. INTERPRETATION: Although N95 respirators appeared to have a protective advantage over surgical masks in laboratory settings, our meta-analysis showed that there were insufficient data to determine definitively whether N95 respirators are superior to surgical masks in protecting health care workers against transmissible acute respiratory infections in clinical settings.",,"['Smith, Jeffrey D.', 'MacDougall, Colin C.', 'Johnstone, Jennie', 'Copes, Ray A.', 'Schwartz, Brian', 'Garber, Gary E.']",,,,
,PMC,"Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)",http://dx.doi.org/10.1074/jbc.M116.716100,PMC4861487,,,"Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC(50) as low as 330 nm. Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection.",,"['Zhou, Nan', 'Pan, Ting', 'Zhang, Junsong', 'Li, Qianwen', 'Zhang, Xue', 'Bai, Chuan', 'Huang, Feng', 'Peng, Tao', 'Zhang, Jianhua', 'Liu, Chao', 'Tao, Liang', 'Zhang, Hui']",,,,
,PMC,Microbial pathogenesis and type III interferons,http://dx.doi.org/10.1016/j.cytogfr.2016.02.005,PMC4899229,,,"The innate immune system possesses a multitude of pathways to sense and respond to microbial pathogens. One such family are the interferons (IFNs), a family of cytokines that are involved in several cellular functions. Type I IFNs are appreciated to be important in several viral and bacterial diseases, while the recently identified type III IFNs (IFNL1, IFNL2, IFNL3, IFNL4) have been studied primarily in the context of viral infection. Viral and bacterial infections however are not mutually exclusive, and often the presence of a viral pathogen increases the pathogenesis of bacterial infection. The role of type III IFN in bacterial and viral-bacterial co-infections has just begun to be explored. In this mini review we discuss type III IFN signaling and its role in microbial pathogenesis with an emphasis on the work that has been conducted with bacterial pathogens.",,"['Cohen, Taylor S', 'Parker, Dane']",,,,
,PMC,CARMA3 is a host factor regulating the balance of inflammatory and antiviral responses against viral infection,http://dx.doi.org/10.1016/j.celrep.2016.02.031,PMC5842788,,,"Host response to RNA virus infection is sensed by RNA sensors such as RIG-I, which induce MAVS-mediated NF-κB and IRF3 activation to promote inflammatory and antiviral responses, respectively. Here, we found that CARMA3, a scaffold protein previously shown to mediate NF-κB activation induced by GPCR and EGFR, positively regulates MAVS-induced NF-κB activation. However, our data suggest that CARMA3 sequesters MAVS from forming high-molecular weight aggregates, thereby suppressing TBK1/IRF3 activation. Interestingly, following NF-κB activation upon virus infection, CARMA3 is targeted for proteasome-dependent degradation, which releases MAVS to activate IRF3. When challenged with Vesicular stomatitis virus or Influenza A virus, CARMA3-deficient mice showed reduced disease symptoms compared to those of wild type mice due to less inflammation and stronger ability to clear infected virus. Together, our studies reveal the role of CARMA3 in regulating the balance of host anti-viral and pro-inflammatory responses against RNA virus infection.",,"['Jiang, Changying', 'Zhou, Zhicheng', 'Quan, Yanping', 'Zhang, Shilei', 'Wang, Tingting', 'Zhao, Xueqiang', 'Morrison, Clayton', 'Heise, Mark T.', 'He, Wenqian', 'Miller, Matthew S.', 'Lin, Xin']",,,,
,PMC,Prophylaxis With a Middle East Respiratory Syndrome Coronavirus (MERS-CoV)–Specific Human Monoclonal Antibody Protects Rabbits From MERS-CoV Infection,http://dx.doi.org/10.1093/infdis/jiw080,PMC4837915,,,"With >1600 documented human infections with Middle East respiratory syndrome coronavirus (MERS-CoV) and a case fatality rate of approximately 36%, medical countermeasures are needed to prevent and limit the disease. We examined the in vivo efficacy of the human monoclonal antibody m336, which has high neutralizing activity against MERS-CoV in vitro. m336 was administered to rabbits intravenously or intranasally before infection with MERS-CoV. Prophylaxis with m336 resulted in a reduction of pulmonary viral RNA titers by 40–9000-fold, compared with an irrelevant control antibody with little to no inflammation or viral antigen detected. This protection in rabbits supports further clinical development of m336.",,"['Houser, Katherine V.', 'Gretebeck, Lisa', 'Ying, Tianlei', 'Wang, Yanping', 'Vogel, Leatrice', 'Lamirande, Elaine W.', 'Bock, Kevin W.', 'Moore, Ian N.', 'Dimitrov, Dimiter S.', 'Subbarao, Kanta']",,,,
,PMC,Oxidation of Membrane Curvature-Regulating Phosphatidylethanolamine Lipid Results in Formation of Bilayer and Cubic Structures,http://dx.doi.org/10.1021/acs.langmuir.5b04332,PMC6559366,,,"Oxidation is associated with conditions related to chronic inflammations and aging. Cubic structures have been observed in the smooth endoplasmic reticulum and mitochondrial membranes of cells under oxidative stress (e.g., tumor cells and virus-infected cells). It has been previously suspected that oxidation can result in the rearrangement of lipids from a fluid lamellar phase to a cubic structure in organelles containing membranes enriched with amphiphiles that have nonzero intrinsic curvature, such as phosphatidylethanolamine (PE) and cardiolipin. This study focuses on the oxidation of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), a lipid that natively forms an inverted hexagonal phase at physiological conditions. The oxidized samples contain an approximately 3:2 molar ratio of nonoxidized to oxidized DOPE. Optical microscopy images collected during the hydration of this mixture from a dried film suggest that the system evolves into a coexistence of a stable fluid lamellar phase and transient square lattice structures with unit cell sizes of 500–600 nm. Small-angle X-ray scattering of the same lipid mixture yielded a body-centered Im3m cubic phase with the lattice parameter of 14.04 nm. On average, the effective packing parameter of the oxidized DOPE species was estimated to be 0.657 ± 0.069 (standard deviation). This suggests that the oxidation of PE leads to a group of species with inverted molecular intrinsic curvature. Oxidation can create amphiphilic subpopulations that potently impact the integrity of the membrane, since negative Gaussian curvature intrinsic to cubic phases can enable membrane destabilization processes",,"['Sankhagowit, Shalene', 'Lee, Ernest Y.', 'Wong, Gerard C. L.', 'Malmstadt, Noah']",,,,
,PMC,Prefusion structure of a human coronavirus spike protein,http://dx.doi.org/10.1038/nature17200,PMC4860016,,,"HKU1 is a human betacoronavirus that causes mild yet prevalent respiratory disease(1) and is related to the zoonotic SARS(2) and MERS(3) betacoronaviruses that have high fatality rates and pandemic potential. Cell tropism and host range is determined in part by the coronavirus spike (S) protein(4), which binds cellular receptors and mediates membrane fusion. As the largest known class I fusion protein, its size and extensive glycosylation have hindered structural studies of the full ectodomain, thus preventing a molecular understanding of its function and limiting development of effective interventions. Here we present the 4.0 Å resolution structure of the trimeric HKU1 S protein determined using single-particle cryo-electron microscopy. In the prefusion conformation, the receptor-binding subunits, S1, rest atop the fusion-mediating subunits, S2, preventing their conformational rearrangement. Surprisingly, the S1 C-terminal domains are interdigitated and form extensive quaternary interactions that occlude surfaces known to bind protein receptors in other coronaviruses. These features, along with the location of the two protease sites known to be important for coronavirus entry, provide a structural basis to support a model of membrane fusion mediated by progressive S protein destabilization through receptor binding and proteolytic cleavage. Additionally, these studies should serve as a foundation for the structure-based design of betacoronavirus vaccine immunogens.",,"['Kirchdoerfer, Robert N.', 'Cottrell, Christopher A.', 'Wang, Nianshuang', 'Pallesen, Jesper', 'Yassine, Hadi M.', 'Turner, Hannah L.', 'Corbett, Kizzmekia S.', 'Graham, Barney S.', 'McLellan, Jason S.', 'Ward, Andrew B.']",,,,
,PMC,Highly Sensitive Assay for Measurement of Arenavirus-cell Attachment,http://dx.doi.org/10.3791/53682,PMC4828211,,,"Arenaviruses are a family of enveloped RNA viruses that cause severe human disease. The first step in the arenavirus life cycle is attachment of viral particles to host cells. While virus-cell attachment can be measured through the use of virions labeled with biotin, radioactive isotopes, or fluorescent dyes, these approaches typically require high multiplicities of infection (MOI) to enable detection of bound virus. We describe a quantitative (q)RT-PCR-based assay that measures Junin virus strain Candid 1 attachment via quantitation of virion-packaged viral genomic RNA. This assay has several advantages including its extreme sensitivity and ability to measure attachment over a large dynamic range of MOIs without the need to purify or label input virus. Importantly, this approach can be easily tailored for use with other viruses through the use of virus-specific qRT-PCR reagents. Further, this assay can be modified to permit measurement of particle endocytosis and genome uncoating. In conclusion, we describe a simple, yet robust assay for highly sensitive measurement of arenavirus-cell attachment.",,"['Klaus, Joseph P.', 'Botten, Jason']",,,,
,PMC,An Acute Immune Response to Middle East Respiratory Syndrome Coronavirus Replication Contributes to Viral Pathogenicity,http://dx.doi.org/10.1016/j.ajpath.2015.10.025,PMC4816712,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in a human with severe pneumonia in 2012. Since then, infections have been detected in >1500 individuals, with disease severity ranging from asymptomatic to severe, fatal pneumonia. To elucidate the pathogenesis of this virus and investigate mechanisms underlying disease severity variation in the absence of autopsy data, a rhesus macaque and common marmoset model of MERS-CoV disease were analyzed. Rhesus macaques developed mild disease, and common marmosets exhibited moderate to severe, potentially lethal, disease. Both nonhuman primate species exhibited respiratory clinical signs after inoculation, which were more severe and of longer duration in the marmosets, and developed bronchointerstitial pneumonia. In marmosets, the pneumonia was more extensive, with development of severe airway lesions. Quantitative analysis showed significantly higher levels of pulmonary neutrophil infiltration and higher amounts of pulmonary viral antigen in marmosets. Pulmonary expression of the MERS-CoV receptor, dipeptidyl peptidase 4, was similar in marmosets and macaques. These results suggest that increased virus replication and the local immune response to MERS-CoV infection likely play a role in pulmonary pathology severity. Together, the rhesus macaque and common marmoset models of MERS-CoV span the wide range of disease severity reported in MERS-CoV–infected humans, which will aid in investigating MERS-CoV disease pathogenesis.",,"['Baseler, Laura J.', 'Falzarano, Darryl', 'Scott, Dana P.', 'Rosenke, Rebecca', 'Thomas, Tina', 'Munster, Vincent J.', 'Feldmann, Heinz', 'de Wit, Emmie']",,,,
,PMC,Convalescent plasma: new evidence for an old therapeutic tool?,http://dx.doi.org/10.2450/2015.0131-15,PMC4781783,,,"Passive immunisation for the prevention and treatment of human infectious diseases can be traced back to the 20(th) century. The recent Ebola virus outbreak in West Africa has turned the spotlight onto the possible use of convalescent whole blood and convalescent plasma in the treatment of infectious diseases because they are the only therapeutic strategy available in some cases, given the unavailability of vaccines, drugs or other specific treatments. Convalescent blood products could be a valid option in the treatment/prophylaxis of several infectious diseases both in association with other drugs/preventive measures and as the only therapy when a specific treatment is not available. However, there are still some issues to consider in determining the advisability of implementing a large-scale convalescent plasma transfusion programme.",,"['Marano, Giuseppe', 'Vaglio, Stefania', 'Pupella, Simonetta', 'Facco, Giuseppina', 'Catalano, Liviana', 'Liumbruno, Giancarlo M.', 'Grazzini, Giuliano']",,,,
,PMC,"Healthcare Workers Emotions, Perceived Stressors and Coping Strategies During a MERS-CoV Outbreak",http://dx.doi.org/10.3121/cmr.2016.1303,PMC4851451,,,"OBJECTIVE: Healthcare workers (HCWs) are at high risk of contracting Middle East respiratory syndrome coronavirus (MERS-CoV) during an epidemic. We explored the emotions, perceived stressors, and coping strategies of healthcare workers who worked during a MERS-CoV outbreak in our hospital. DESIGN: A cross-sectional descriptive survey design. SETTING: A tertiary care hospital. PARTICIPANTS: HCWs (150) who worked in high risk areas during the April–May 2014 MERS-CoV outbreak that occurred in Jeddah, Saudi Arabia. METHODS: We developed and administered a “MERS-CoV staff questionnaire” to study participants. The questionnaire consisted of 5 sections with 72 questions. The sections evaluated hospital staffs emotions, perceived stressors, factors that reduced their stress, coping strategies, and motivators to work during future outbreaks. Responses were scored on a scale from 0–3. The varying levels of stress or effectiveness of measures were reported as mean and standard deviation, as appropriate. RESULTS: Completed questionnaires were returned by 117 (78%) of the participants. The results had many unique elements. HCWs ethical obligation to their profession pushed them to continue with their jobs. The main sentiments centered upon fear of personal safety and well-being of colleagues and family. Positive attitudes in the workplace, clinical improvement of infected colleagues, and stoppage of disease transmission among HCWs after adopting strict protective measures alleviated their fear and drove them through the epidemic. They appreciated recognition of their efforts by hospital management and expected similar acknowledgment, infection control guidance, and equipment would entice them to work during future epidemics. CONCLUSION: The MERS-CoV outbreak was a distressing time for our staff. Hospitals can enhance HCWs experiences during any future MERS-CoV outbreak by focusing on the above mentioned aspects.",,"['Khalid, Imran', 'Khalid, Tabindeh J.', 'Qabajah, Mohammed R.', 'Barnard, Aletta G.', 'Qushmaq, Ismael A.']",,,,
,PMC,Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection,http://dx.doi.org/10.1586/14789450.2016.1147353,PMC4919574,,,"The integration of proteomic methods to virology has facilitated a significant breadth of biological insight into mechanisms of virus replication, antiviral host responses and viral subversion of host defenses. Throughout the course of infection, these cellular mechanisms rely heavily on the formation of temporally and spatially regulated virus–host protein–protein interactions. Reviewed here are proteomic-based approaches that have been used to characterize this dynamic virus–host interplay. Specifically discussed are the contribution of integrative mass spectrometry, antibody-based affinity purification of protein complexes, cross-linking and protein array techniques for elucidating complex networks of virus–host protein associations during infection with a diverse range of RNA and DNA viruses. The benefits and limitations of applying proteomic methods to virology are explored, and the contribution of these approaches to important biological discoveries and to inspiring new tractable avenues for the design of antiviral therapeutics is highlighted.",,"['Lum, Krystal K', 'Cristea, Ileana M']",,,,
,PMC,Factors in the Selection of Surface Disinfectants for Use in a Laboratory Animal Setting,,PMC4783637,,,"Because surface disinfectants are an important means of pathogen control within laboratory animal facilities, these products must have an appropriate spectrum of antimicrobial activity. However, many other factors must also be considered, including effects on human health, environmental safety, and animal behavior. Aqueous solutions of sodium hypochlorite often are considered to be the ‘gold standard’ for surface disinfection, but these products can be corrosive, caustic, and aversive in odor. This study was designed to identify disinfectants that are as effective as hypochlorite solutions but more acceptable for use in a laboratory animal setting. An antiviral disinfectant-efficacy assay was developed by using viral vectors that expressed green fluorescence protein as surrogates for wild-type viruses of concern in laboratory animals. Efficacy testing revealed that most of the products were highly effective when used against viral vectors in suspension. However, when the disinfectants were challenged by buffering virus in protein or drying virus on nonporous surfaces, the hypochlorite and peroxymonosulfate products performed the best. Review of safety data sheets for the agents indicated that a peroxide-based product was considerably safer than the other products tested and that the pH of most products was not conducive to disposal down a drain. Behavioral testing of Swiss Webster, C57Bl/6, and BALB/c mice showed that the hypochlorite- and peroxide-based products were clearly aversive, given that the mice consistently avoided these products. All of these factors must be considered when choosing the appropriate disinfectant.",,"['Campagna, Michael V', 'Faure-Kumar, Emmanuelle', 'Treger, Janet A', 'Cushman, Jesse D', 'Grogan, Tristan R', 'Kasahara, Noriyuki', 'Lawson, Gregory W']",,,,
,PMC,NB protein does not affect influenza B virus replication in vitro and is not required for replication in or transmission between ferrets,http://dx.doi.org/10.1099/jgv.0.000386,PMC5381391,,,"The influenza B virus encodes a unique protein, NB, a membrane protein whose function in the replication cycle is not, as yet, understood. We engineered a recombinant influenza B virus lacking NB expression, with no concomitant difference in expression or activity of viral neuraminidase (NA) protein, an important caveat since NA is encoded on the same segment and initiated from a start codon just 4 nt downstream of NB. Replication of the virus lacking NB was not different to wild-type virus with full-length NB in clonal immortalized or complex primary cell cultures. In the mouse model, virus lacking NB induced slightly lower IFN-α levels in infected lungs, but this did not affect virus titres or weight loss. In ferrets infected with a mixture of viruses that did or did not express NB, there was no fitness advantage for the virus that retained NB. Moreover, virus lacking NB protein was transmitted following respiratory droplet exposure of sentinel animals. These data suggest no role for NB in supporting replication or transmission in vivo in this animal model. The role of NB and the nature of selection to retain it in all natural influenza B viruses remain unclear.",,"['Elderfield, Ruth A.', 'Koutsakos, Marios', 'Frise, Rebecca', 'Bradley, Konrad', 'Ashcroft, Jonathan', 'Miah, Shanhjahan', 'Lackenby, Angie', 'Barclay, Wendy S.']",,,,
,PMC,Early events in the generation of autophagosomes are required for the formation of membrane structures involved in hepatitis C virus genome replication,http://dx.doi.org/10.1099/jgv.0.000387,PMC5115167,,,"Hepatitis C virus (HCV) infection has been shown to induce autophagy but the mechanisms underpinning this process remain to be elucidated. Induction of autophagy requires the class III phosphatidylinositol 3-kinase, Vps34, which produces phosphatidylinositol 3-phosphate (PI3P) within the endoplasmic reticulum (ER) membrane. This recruits proteins with PI3P binding domains such as the double-FYVE-containing protein 1 (DFCP1). DFCP1 generates cup–shaped protrusions from the ER membrane, termed omegasomes, which provide a platform for the production of autophagosomes. Here we present data demonstrating that both Vps34 and DFCP1 are required for HCV genome replication, in the context of both a subgenomic replicon and virus infection, but did not affect virus entry or initial translation. Using live cell fluorescence microscopy we demonstrated that early during HCV infection the nascent viral genome replication complexes (identified by using non-structural protein NS5A as a marker) transiently colocalize with DFCP1-positive punctae (omegasomes), before the two structures move apart from each other. This observation is reminiscent of the transient association of LC3 and DFCP1 during omegasome formation, and therefore we propose that omegasomes are utilized by HCV to generate the double-membrane vesicles which are the hallmark of HCV replication complexes.",,"['Mohl, Bjorn-Patrick', 'Bartlett, Christopher', 'Mankouri, Jamel', 'Harris, Mark']",,,,
,PMC,Impact of viral infection on acute exacerbation of asthma in out-patient clinics: a prospective study,http://dx.doi.org/10.21037/jtd.2016.02.76,PMC4805813,,,"BACKGROUND: The prevalence of viral infection triggering asthma exacerbation and its impact on the symptoms and duration of exacerbation are unclear. METHODS: Asthma and healthy control subjects were recruited from the First Affiliated Hospital of Guangzhou Medical University between February 2012 and February 2013. Nasal swabs were collected, and respiratory viruses were detected by polymerase chain reaction (PCR). All patients completed questionnaires and a lung function test. Some were followed up for 4 weeks, and symptom changes were evaluated via asthma diaries. RESULTS: In total, 70 patients with acute asthma exacerbations were recruited. Among them, 34 patients (48.6%) completed the 4-week follow-up study. Another 65 patients with stable asthma and 134 healthy volunteers were also included in this study. The rate of positive viral detection via PCR in acute asthma exacerbation patients was 34.2% (24/70), which is significantly higher than that of stable asthma (12/65; 18.5%; P=0.038) and normal control patients (18/134; 13.4%; P<0.001). Among the viral-positive subjects, the number of viral copies was significantly higher in acute asthma exacerbation patients [(5.00±4.63) ×10(7) copies/L] (mean ± SD) than those in stable asthma patients [(1.24±1.44) ×10(6) copies/L; P<0.001] or in healthy controls [(1.44±0.44) ×10(6) copies/L; P<0.001], whose viral loads were not significantly different from one another (P=0.774). During the 4-week follow-up period, the cough scores on days 1 and 3 were significantly higher in the viral-positive group than in the viral-negative group (day 1: P=0.016; day 3: P=0.004). However, there were no significant differences between these two groups for other tested symptoms, such as dyspnea and total recovery time (P>0.05). CONCLUSIONS: Respiratory viruses may be involved in acute asthma exacerbations, inducing more prominent and persistent cough symptoms.",,"['Liao, Hua', 'Yang, Zifeng', 'Yang, Chunguang', 'Tang, Yan', 'Liu, Shengming', 'Guan, Wenda', 'Chen, Rongchang']",,,,
,PMC,Endocrinopathy and Aging in Ferrets,http://dx.doi.org/10.1177/0300985815623621,PMC5397995,,,"Ferrets have become more popular as household pets and as animal models in biomedical research in the past 2 decades. The average life span of ferrets is about 5-11 years with onset of geriatric diseases between 3-4 years including endocrinopathies, neoplasia, gastrointestinal diseases, cardiomyopathy, splenomegaly, renal diseases, dental diseases, and cataract. Endocrinopathies are the most common noninfectious disease affecting middle-aged and older ferrets. Spontaneous neoplasms affecting the endocrine system of ferrets appear to be increasing in prevalence with a preponderance toward proliferative lesions in the adrenal cortex and pancreatic islet cells. Diet, gonadectomy, and genetics may predispose ferrets to an increased incidence of these endocrinopathies. These functional proliferative lesions cause hypersecretion of hormones that alter the physiology and metabolism of the affected ferrets resulting in a wide range of clinical manifestations. However, there is an apparent dearth of information available in the literature about the causal relationship between aging and neoplasia in ferrets. This review provides a comprehensive overview of the anatomy and physiology of endocrine organs, disease incidence, age at diagnosis, clinical signs, pathology, and molecular markers available for diagnosis of various endocrine disorders in ferrets.",,"['Bakthavatchalu, V.', 'Muthupalani, S.', 'Marini, R. P.', 'Fox, J. G.']",,,,
,PMC,Consortia’s critical role in developing medical countermeasures for re-emerging viral infections: a USA perspective,http://dx.doi.org/10.2217/fvl-2015-0011,PMC4912138,,,"Viral infections, such as Ebola, severe acute respiratory syndrome/Middle East respiratory syndrome and West Nile virus have emerged as a serious health threat with no effective therapies. These infections have little commercial potential and are not a high priority for the pharmaceutical industry. However, the academic community has been active in this area for many years. The challenge is how to take this academic virology knowledge into a drug discovery and development domain. One approach is the use of consortia and public–private partnerships – this article highlights ongoing efforts in the USA. Public funds, such as those from government sources, can support research efforts that do not to appear to have commercial value. The key to success is finding a way to combine the different cultural and operational values and reward systems into a productive collaboration to identify new antivirals.",,"['Everts, Maaike', 'Suto, Mark J', 'Painter, George R', 'Whitley, Richard J']",,,,
,PMC,New Verapamil Analogs Inhibit Intracellular Mycobacteria without Affecting the Functions of Mycobacterium-Specific T Cells,http://dx.doi.org/10.1128/AAC.01567-15,PMC4775996,,,"There is a growing interest in repurposing mycobacterial efflux pump inhibitors, such as verapamil, for tuberculosis (TB) treatment. To aid in the design of better analogs, we studied the effects of verapamil on macrophages and Mycobacterium tuberculosis-specific T cells. Macrophage activation was evaluated by measuring levels of nitric oxide, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and gamma interferon (IFN-γ). Since verapamil is a known autophagy inducer, the roles of autophagy induction in the antimycobacterial activities of verapamil and norverapamil were studied using bone marrow-derived macrophages from ATG5(flox/flox) (control) and ATG5(flox/flox) Lyz-Cre mice. Our results showed that despite the well-recognized effects of verapamil on calcium channels and autophagy, its action on intracellular M. tuberculosis does not involve macrophage activation or autophagy induction. Next, the effects of verapamil and norverapamil on M. tuberculosis-specific T cells were assessed using flow cytometry following the stimulation of peripheral blood mononuclear cells from TB-skin-test-positive donors with M. tuberculosis whole-cell lysate for 7 days in the presence or absence of drugs. We found that verapamil and norverapamil inhibit the expansion of M. tuberculosis-specific T cells. Additionally, three new verapamil analogs were found to inhibit intracellular Mycobacterium bovis BCG, and one of the three analogs (KSV21) inhibited intracellular M. tuberculosis replication at concentrations that did not inhibit M. tuberculosis-specific T cell expansion. KSV21 also inhibited mycobacterial efflux pumps to the same degree as verapamil. More interestingly, the new analog enhances the inhibitory activities of isoniazid and rifampin on intracellular M. tuberculosis. In conclusion, KSV21 is a promising verapamil analog on which to base structure-activity relationship studies aimed at identifying more effective analogs.",,"['Abate, Getahun', 'Ruminiski, Peter G.', 'Kumar, Malkeet', 'Singh, Kawaljit', 'Hamzabegovic, Fahreta', 'Hoft, Daniel F.', 'Eickhoff, Christopher S.', 'Selimovic, Asmir', 'Campbell, Mary', 'Chibale, Kelly']",,,,
,PMC,Application of Virus-Like Particles (VLP) to NMR Characterization of Viral Membrane Protein Interactions,http://dx.doi.org/10.1007/s10858-016-0025-1,PMC4826305,,,"The membrane proteins of viruses play critical roles in the virus life cycle and are attractive targets for therapeutic intervention. Virus Like Particles (VLP) present the possibility to study the biochemical and biophysical properties of viral membrane proteins in their native environment. Specifically, the VLP constructs contain the entire protein sequence and are comprised of native membrane components including lipids, cholesterol, carbohydrates and cellular proteins. In this study we prepare VLP containing full-length hemagglutinin (HA) or neuraminidase (NA) from influenza and characterize their interactions with small molecule inhibitors. Using HA-VLP, we first show that VLP samples prepared using the standard sucrose gradient purification scheme contain significant amounts of serum proteins, which exhibit high potential for non-specific interactions, thereby complicating NMR studies of ligand-target interactions. We then show that the serum contaminants may be largely removed with the addition of a gel filtration chromatography step. Next, using HA-VLP we demonstrate that WaterLOGSY (WL) NMR is significantly more sensitive than Saturation Transfer Difference (STD) NMR for the study of ligand interactions with membrane bound targets. In addition, we compare the ligand orientation to HA embedded in VLP with that of recombinant HA by STD NMR. In a subsequent step, using NA-VLP we characterize the kinetic and binding properties of substrate analogs and inhibitors of NA, including study of the H274Y-NA mutant, which leads to wide spread resistance to current influenza antivirals. In summary, our work suggests that VLP have high potential to become standard tools in biochemical and biophysical studies of viral membrane proteins, particularly when VLP are highly purified and combined with control VLP containing native membrane proteins.",,"['Antanasijevic, Aleksandar', 'Kingsley, Carolyn', 'Basu, Arnab', 'Bowlin, Terry L.', 'Rong, Lijun', 'Caffrey, Michael']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00104-16,PMC4810670,,,,,,,,,
,PMC,Activation of RNase L by Murine Coronavirus in Myeloid Cells Is Dependent on Basal Oas Gene Expression and Independent of Virus-Induced Interferon,http://dx.doi.org/10.1128/JVI.03036-15,PMC4810646,,,"The oligoadenylate synthetase (OAS)-RNase L pathway is a potent interferon (IFN)-induced antiviral activity. Upon sensing double-stranded RNA, OAS produces 2′,5′-oligoadenylates (2-5A), which activate RNase L. Murine coronavirus (mouse hepatitis virus [MHV]) nonstructural protein 2 (ns2) is a 2′,5′-phosphodiesterase (PDE) that cleaves 2-5A, thereby antagonizing RNase L activation. PDE activity is required for robust replication in myeloid cells, as a mutant of MHV (ns2(H126R)) encoding an inactive PDE fails to antagonize RNase L activation and replicates poorly in bone marrow-derived macrophages (BMM), while ns2(H126R) replicates to high titer in several types of nonmyeloid cells, as well as in IFN receptor-deficient (Ifnar1(−/−)) BMM. We reported previously that myeloid cells express significantly higher basal levels of OAS transcripts than nonmyeloid cells. Here, we investigated the contributions of Oas gene expression, basal IFN signaling, and virus-induced IFN to RNase L activation. Infection with ns2(H126R) activated RNase L in Ifih1(−/−) BMM to a similar extent as in wild-type (WT) BMM, despite the lack of IFN induction in the absence of MDA5 expression. However, ns2(H126R) failed to induce RNase L activation in BMM treated with IFNAR1-blocking antibody, as well as in Ifnar1(−/−) BMM, both expressing low basal levels of Oas genes. Thus, activation of RNase L does not require virus-induced IFN but rather correlates with adequate levels of basal Oas gene expression, maintained by basal IFN signaling. Finally, overexpression of RNase L is not sufficient to compensate for inadequate basal OAS levels. IMPORTANCE The oligoadenylate synthetase (OAS)-RNase L pathway is a potent antiviral activity. Activation of RNase L during murine coronavirus (mouse hepatitis virus [MHV]) infection of myeloid cells correlates with high basal Oas gene expression and is independent of virus-induced interferon secretion. Thus, our data suggest that cells with high basal Oas gene expression levels can activate RNase L and thereby inhibit virus replication early in infection upon exposure to viral double-stranded RNA (dsRNA) before the induction of interferon and prior to transcription of interferon-stimulated antiviral genes. These findings challenge the notion that activation of the OAS-RNase L pathway requires virus to induce type I IFN, which in turn upregulates OAS gene expression, as well as to provide dsRNA to activate OAS. Our data further suggest that myeloid cells may serve as sentinels to restrict viral replication, thus protecting other cell types from infection.",,"['Birdwell, L. Dillon', 'Zalinger, Zachary B.', 'Li, Yize', 'Wright, Patrick W.', 'Elliott, Ruth', 'Rose, Kristine M.', 'Silverman, Robert H.', 'Weiss, Susan R.']",,,,
,PMC,Isolation and Characterization of a Novel Bat Coronavirus Closely Related to the Direct Progenitor of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.02582-15,PMC4810638,,,"We report the isolation and characterization of a novel bat coronavirus which is much closer to the severe acute respiratory syndrome coronavirus (SARS-CoV) in genomic sequence than others previously reported, particularly in its S gene. Cell entry and susceptibility studies indicated that this virus can use ACE2 as a receptor and infect animal and human cell lines. Our results provide further evidence of the bat origin of the SARS-CoV and highlight the likelihood of future bat coronavirus emergence in humans.",,"['Yang, Xing-Lou', 'Hu, Ben', 'Wang, Bo', 'Wang, Mei-Niang', 'Zhang, Qian', 'Zhang, Wei', 'Wu, Li-Jun', 'Ge, Xing-Yi', 'Zhang, Yun-Zhi', 'Daszak, Peter', 'Wang, Lin-Fa', 'Shi, Zheng-Li']",,,,
,PMC,The Synthetic Antiviral Drug Arbidol Inhibits Globally Prevalent Pathogenic Viruses,http://dx.doi.org/10.1128/JVI.02077-15,PMC4810626,,,"Arbidol (ARB) is a synthetic antiviral originally developed to combat influenza viruses. ARB is currently used clinically in several countries but not in North America. We have previously shown that ARB inhibits in vitro hepatitis C virus (HCV) by blocking HCV entry and replication. In this report, we expand the list of viruses that are inhibited by ARB and demonstrate that ARB suppresses in vitro infection of mammalian cells with Ebola virus (EBOV), Tacaribe arenavirus, and human herpesvirus 8 (HHV-8). We also confirm suppression of hepatitis B virus and poliovirus by ARB. ARB inhibited EBOV Zaire Kikwit infection when added before or at the same time as virus infection and was less effective when added 24 h after EBOV infection. Experiments with recombinant vesicular stomatitis virus (VSV) expressing the EBOV Zaire glycoprotein showed that infection was inhibited by ARB at early stages, most likely at the level of viral entry into host cells. ARB inhibited HHV-8 replication to a similar degree as cidofovir. Our data broaden the spectrum of antiviral efficacy of ARB to include globally prevalent viruses that cause significant morbidity and mortality. IMPORTANCE There are many globally prevalent viruses for which there are no licensed vaccines or antiviral medicines. Some of these viruses, such as Ebola virus or members of the arenavirus family, rapidly cause severe hemorrhagic diseases that can be fatal. Other viruses, such as hepatitis B virus or human herpesvirus 8 (HHV-8), establish persistent infections that cause chronic illnesses, including cancer. Thus, finding an affordable, effective, and safe drug that blocks many viruses remains an unmet medical need. The antiviral drug arbidol (ARB), already in clinical use in several countries as an anti-influenza treatment, has been previously shown to suppress the growth of many viruses. In this report, we expand the list of viruses that are blocked by ARB in a laboratory setting to include Ebola virus, Tacaribe arenavirus, and HHV-8, and we propose ARB as a broad-spectrum antiviral drug that may be useful against hemorrhagic viruses.",,"['Pécheur, Eve-Isabelle', 'Borisevich, Viktoriya', 'Halfmann, Peter', 'Morrey, John D.', 'Smee, Donald F.', 'Prichard, Mark', 'Mire, Chad E.', 'Kawaoka, Yoshihiro', 'Geisbert, Thomas W.', 'Polyak, Stephen J.']",,,,
,PMC,Advances in addressing technical challenges of point-of-care diagnostics in resource-limited settings,http://dx.doi.org/10.1586/14737159.2016.1142877,PMC4943866,,,"The striking prevalence of HIV, TB and malaria, as well as outbreaks of emerging infectious diseases, such as influenza A (H7N9), Ebola and MERS, poses great challenges for patient care in resource-limited settings (RLS). However, advanced diagnostic technologies cannot be implemented in RLS largely due to economic constraints. Simple and inexpensive point-of-care (POC) diagnostics, which rely less on environmental context and operator training, have thus been extensively studied to achieve early diagnosis and treatment monitoring in non-laboratory settings. Despite great input from material science, biomedical engineering and nanotechnology for developing POC diagnostics, significant technical challenges are yet to be overcome. Summarized here are the technical challenges associated with POC diagnostics from a RLS perspective and the latest advances in addressing these challenges are reviewed.",,"['Wang, ShuQi', 'Lifson, Mark A.', 'Inci, Fatih', 'Liang, Li-Guo', 'Sheng, Ye-Feng', 'Demirci, Utkan']",,,,
,PMC,"Communicating about the Middle East respiratory syndrome outbreak to the international community and in-country foreigners, Republic of Korea, 2015",http://dx.doi.org/10.5365/WPSAR.2015.6.4.002,PMC5052895,,,,,"['Lee, Minwon', 'Sohn, Jooyoung', 'Park, Kidong']",,,,
,PMC,"Emotional Acceptance, Inflammation, and Sickness Symptoms Across the First Two Years Following Breast Cancer Diagnosis",http://dx.doi.org/10.1016/j.bbi.2016.02.018,PMC4917434,,,"PURPOSE: Breast cancer diagnosis and treatment are associated with increased inflammatory activity, which can induce sickness symptoms. We examined whether emotional acceptance moderates the association between proinflammatory cytokines and self-reported sickness symptoms in women recently diagnosed with breast cancer. METHODS: Women (N = 136) diagnosed with stage 0-III breast cancer within the previous 6 months provided plasma samples and completed the FACT: Physical Well-Being Scale, as well as the Acceptance of Emotion Scale every 3 months for 2 years. At each time point, we quantified interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α using a high sensitivity multiplex assay. RESULTS: Higher within-subject mean TNF-α across all time-points predicted higher mean sickness symptoms. At individual time-points, higher IL-6 and IL-8 levels were associated with higher sickness symptoms. Mean emotional acceptance across all time-points moderated the relationship between mean IL-8 and sickness symptoms, with sickness symptoms remaining persistently high in women with low emotional acceptance even when IL-8 levels were low. At individual time-points, emotional acceptance positively moderated the correlations of IL-8 and TNF-α with sickness symptoms, such that the associations between higher levels of these proinflammatory cytokines and higher sickness symptoms were attenuated when emotional acceptance was high. CONCLUSION: Emotional acceptance was shown for the first time to moderate the associations of cytokines with sickness symptoms in breast cancer patients over time following diagnosis and treatment. The association between emotional acceptance and sickness symptoms was significantly different from zero but relatively small in comparison to the range of sickness symptoms. Results suggest that targeting emotion regulation may help to break the cycle between inflammation and sickness symptoms in women with breast cancer.",,"['Reed, Rebecca G.', 'Weihs, Karen L.', 'Sbarra, David A.', 'Breen, Elizabeth C.', 'Irwin, Michael R.', 'Butler, Emily A.']",,,,
,PMC,When your cap matters: Structural insights into self vs non-self recognition of 5′ RNA by immunomodulatory host proteins,http://dx.doi.org/10.1016/j.sbi.2016.02.001,PMC5218996,,,"Cytosolic recognition of viral RNA is important for host innate immune responses. Differential recognition of self vs non-self RNA is a considerable challenge as the inability to differentiate may trigger aberrant immune responses. Recent work identified the composition of the RNA 5′, including the 5′ cap and its methylation state, as an important determinant of recognition by the host. Recent studies have advanced our understanding of the modified 5′ RNA recognition and viral antagonism of RNA receptors. Here, we will discuss RIG-I and IFIT proteins as examples of host proteins that detect dsRNA and ssRNA, respectively.",,"['Leung, Daisy W.', 'Amarasinghe, Gaya K.']",,,,
,PMC,Practical ‘modular design’ research of emergency drug supplies in hospitals,http://dx.doi.org/10.1136/ejhpharm-2015-000833,PMC6451481,,,"OBJECTIVES: To determine an effective framework for supplying emergency drugs under various scenarios using ‘modular design’ and information technology. Additionally, medicinal safety was improved by combining pharmacy monitoring with a safety alert system for medication. METHODS: Data from various emergency events and details of the disease related to the incident were analysed using Cluster, Delphi and Decision analyses. The optimal drug combination was determined and then divided into the different modules. We established the ‘drug supply expedited system in emergencies’ based on the above modules, and we organised emergency drills to verify the system's effectiveness and to improve efficiency. Pharmaceutical care services were performed by rehearsing the unexpected emergency incident and associated pharmaceutical care. RESULTS: We developed a drug supply framework for ‘traffic accidents, poisoning first aid, natural disasters, epidemics and mass disturbances’ and established an ‘emergency drug supply expedited system’. We quickly equipped the drugs that were needed for the special emergency events, and we developed a ‘green channel’ between the emergency and drug supply centres. Medication safety was also important for the emergencies, and clinical pharmacists played a role in medicating the safety service personnel. The utility of our findings was demonstrated through several emergency drills. CONCLUSIONS: In this study, we explored the optimal drug supply and pharmacy assistance models for emergency medicine. The clinical innovation of this study was that we provided a modular supply of medical supplies for traffic accidents. We also established a drug supply information system. This study provided effective reference values for emergency drug therapy.",,"['Song, Chao', 'Yang, Jing', 'Zhang, Xiao-Li', 'Zheng, Lei', 'Yang, Chuan-Ying']",,,,
,PMC,Contraction of the type I IFN locus and unusual constitutive expression of IFN-α in bats,http://dx.doi.org/10.1073/pnas.1518240113,PMC4790985,,,"Bats harbor many emerging and reemerging viruses, several of which are highly pathogenic in other mammals but cause no clinical signs of disease in bats. To determine the role of interferons (IFNs) in the ability of bats to coexist with viruses, we sequenced the type I IFN locus of the Australian black flying fox, Pteropus alecto, providing what is, to our knowledge, the first gene map of the IFN region of any bat species. Our results reveal a highly contracted type I IFN family consisting of only 10 IFNs, including three functional IFN-α loci. Furthermore, the three IFN-α genes are constitutively expressed in unstimulated bat tissues and cells and their expression is unaffected by viral infection. Constitutively expressed IFN-α results in the induction of a subset of IFN-stimulated genes associated with antiviral activity and resistance to DNA damage, providing evidence for a unique IFN system that may be linked to the ability of bats to coexist with viruses.",,"['Zhou, Peng', 'Tachedjian, Mary', 'Wynne, James W.', 'Boyd, Victoria', 'Cui, Jie', 'Smith, Ina', 'Cowled, Christopher', 'Ng, Justin H. J.', 'Mok, Lawrence', 'Michalski, Wojtek P.', 'Mendenhall, Ian H.', 'Tachedjian, Gilda', 'Wang, Lin-Fa', 'Baker, Michelle L.']",,,,
,PMC,Postobstructive Pneumonia: An Underdescribed Syndrome,http://dx.doi.org/10.1093/cid/civ1212,PMC4803103,,,"Background. Postobstructive community-acquired pneumonia (PO-CAP) is relatively common in clinical practice. The clinical syndrome is poorly defined, and the role of infection as a cause of the infiltrate is uncertain. We prospectively studied patients with PO-CAP and compared them to a cohort of patients with bacterial community-acquired pneumonia (B-CAP). Methods. We prospectively studied patients hospitalized for CAP; 5.4% had PO-CAP, defined as a pulmonary infiltrate occurring distal to an obstructed bronchus. Sputum and blood cultures, viral polymerase chain reaction, urinary antigen tests, and serum procalcitonin (PCT) were done in nearly all cases. Clinical and laboratory characteristics of patients with PO-CAP were compared to those of patients with B-CAP. Results. In a 2-year period, we identified 30 patients with PO-CAP. Compared to patients with B-CAP, patients with PO-CAP had longer duration of symptoms (median, 14 vs 5 days; P < .001). Weight loss and cavitary lesions were more common (P < .01 for both comparisons) and leukocytosis was less common (P < .01) in patients with PO-CAP. A bacterial pathogen was implicated in only 3 (10%) PO-CAP cases. PCT was <0.25 ng/mL in 19 (63.3%) patients. Although no differences were observed in disease severity or rates of intensive care unit admissions, 30-day mortality was significantly higher in PO-CAP vs B-CAP (40.0% vs 11.7%; P < .01). Conclusions. Although there is substantial overlap, PO-CAP is a clinical entity distinct from B-CAP; a bacterial cause was identified in only 10% of patients. Our study has important implications for the clinical recognition of patients with PO-CAP, the role of microorganisms as etiologic agents, and the use of antibiotic therapy.",,"['Abers, Michael S.', 'Sandvall, Barcleigh P.', 'Sampath, Rahul', 'Zuno, Carlo', 'Uy, Natalie', 'Yu, Victor L.', 'Stager, Charles E.', 'Musher, Daniel M.']",,,,
,PMC,Mechanistic Models of Infectious Disease and Their Impact on Public Health,http://dx.doi.org/10.1093/aje/kww021,PMC5006438,,,"From the 1930s through the 1940s, Lowell Reed and Wade Hampton Frost used mathematical models and mechanical epidemic simulators as research tools and to teach epidemic theory to students at the Johns Hopkins Bloomberg School of Public Health (then the School of Hygiene and Public Health). Since that time, modeling has become an integral part of epidemiology and public health. Models have been used for explanatory and inferential purposes, as well as in planning and implementing public health responses. In this article, we review a selection of developments in the history of modeling of infectious disease dynamics over the past 100 years. We also identify trends in model development and use and speculate as to the future use of models in infectious disease dynamics.",,"['Lessler, Justin', 'Cummings, Derek A. T.']",,,,
,PMC,Global Health Education,http://dx.doi.org/10.1093/swr/svw001,PMC4885033,,,,,"['Williams, James Herbert', 'Des Marais, Eric A.']",,,,
,PMC,Recovery of renal function after long-term dialysis and resolution of cardiomyopathy in a patient with aHUS receiving eculizumab,http://dx.doi.org/10.1136/bcr-2015-213928,PMC4840264,,,"We present the case of a 18-month-old girl with renal and cardiac manifestations of atypical haemolytic uraemic syndrome (aHUS), and a novel complement factor H mutation. Transient haematological remission was achieved with intensive plasmapheresis, but cardiac function deteriorated and renal function was not restored. Initiation of eculizumab after 6 months of dialysis significantly improved organ function. At 43 months after presentation, haematological values had normalised and cardiac function had improved. Dialysis was discontinued after 10 months (the longest reported time in a patient with aHUS) and the estimated glomerular filtration rate had recovered to 70 mL/min/1.73 m(2). In conclusion, treatment of aHUS with eculizumab, even after long-term dialysis, can significantly improve renal function. Discontinuation of dialysis and resolution of cardiac function has implications on the potential recovery and treatment choice of such patients. Earlier initiation of eculizumab, however, might have prevented the irreversible renal sclerosis and cardiac dysfunction.",,"['Emirova, Khadizha', 'Volokhina, Elena', 'Tolstova, Evgenia', 'van den Heuvel, Bert']",,,,
,PMC,"Biosynthesis, Trafficking and Secretion of Pro-opiomelanocortin-derived peptides",http://dx.doi.org/10.1530/JME-15-0323,PMC4899099,,,"Pro-opiomelanocortin (POMC) is a prohormone that encodes multiple smaller peptide hormones within its structure. These peptide hormones can be generated by cleavage of POMC at basic-residue cleavage sites by prohormone converting enzymes in the regulated secretory pathway of POMC synthesizing endocrine cells and neurons. The peptides are stored inside the cells in dense core secretory granules until released in a stimulus dependent manner. The complexity of the regulation of the biosynthesis, trafficking and secretion of POMC and its peptides reflect an impressive level of control over many factors involved in the ultimate role of POMC expressing cells, i.e. to produce a range of different biologically active peptide hormones ready for action when signaled by the body. From the discovery of POMC as the precursor to ACTH and β-Lipotropin in the late 1970s to our current knowledge, the understanding of POMC physiology remains a monumental body of work that has provided insight into many aspects of molecular endocrinology. In this chapter, we describe the intracellular trafficking of POMC in endocrine cells, its sorting into dense core secretory granules and transport of these granules to the regulated secretory pathway. Additionally, we review the enzymes involved in the maturation of POMC to its various peptides and the mechanisms involved in the differential processing of POMC in different cell types. Finally, we highlight studies pertaining to the regulation of ACTH secretion in the anterior and intermediate pituitary and POMC neurons of the hypothalamus.",,"['Cawley, Niamh X.', 'Li, Zhaojin', 'Loh, Y. Peng']",,,,
,PMC,Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1016/j.coviro.2016.01.011,PMC4821769,,,"The recent emergence of the Middle East respiratory syndrome (MERS)-CoV, a close relative of the Severe Acute respiratory syndrome (SARS)-CoV, both of which caused a lethal respiratory infection in humans, reinforces the need for further understanding of coronavirus pathogenesis and the host immune response. These viruses have evolved diverse strategies to evade and block host immune responses, facilitating infection and transmission. Pathogenesis following infection with these viruses is characterized by a marked delay in the induction of Type I interferon (IFN I) and, subsequently, by a poor adaptive immune response. Therapies that expedite IFN I induction as well as interventions that antagonize immunoevasive virus proteins are thus promising candidates for immune modulation.",,"['Vijay, Rahul', 'Perlman, Stanley']",,,,
,PMC,"Quarterly intrinsic disorder digest (January-February-March, 2014)",http://dx.doi.org/10.1080/21690707.2016.1153395,PMC5314902,,,"This is the 5(th) issue of the Digested Disorder series that represents a reader's digest of the scientific literature on intrinsically disordered proteins. We continue to use only 2 criteria for inclusion of a paper to this digest: The publication date (a paper should be published within the covered time frame) and the topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the first quarter of 2014; i.e., during the period of January, February, and March of 2014. Similar to previous issues, the papers are grouped hierarchically by topics they cover, and for each of the included papers a short description is given on its major findings.",,"['DeForte, Shelly', 'Reddy, Krishna D.', 'Uversky, Vladimir N.']",,,,
,PMC,Impact of Environmental Enrichment Devices on NTP In Vivo Studies,http://dx.doi.org/10.1177/0192623315625330,PMC4785058,,,"The goal of this study was to determine whether the use of nesting material or polycarbonate shelters, as enrichment devices would have an impact on endpoints commonly measured during the conduct of the National Toxicology Program (NTP) 13-week studies. The study design was consistent with the NTP 13-week toxicity studies. Harlan Sprague Dawley (HSD) rats and their offspring, and B6C3F1/N mice were assigned to control (unenriched) and enriched experimental groups. Body weight, food and water consumption, behavioral observations, fecal content, clinical pathology, gross pathology, organ weights, and histopathology were evaluated. Enriched male mice and male and female rats exhibited decreased feed intake without a subsequent decrease in body weight; this may have been the result of the nesting material reducing the effect of cold stress thereby allowing for more efficient use of feed. There were statistical differences in some hematological parameters, however these were not considered physiologically relevant since all values were within the normal range. Gross pathology and histopathological findings were background changes and were not considered enrichment-related. Nesting material and shelters were used frequently and consistently and allowed animals to display species typical behavior. There was no significant impact on commonly measured endpoints in HSD rats and B6C3F1/N mice given enrichment devices.",,"['Churchill, Sheba R.', 'Morgan, Daniel L.', 'Kissling, Grace E.', 'Travlos, Gregory S.', 'King-Herbert, Angela P.']",,,,
,PMC,Children hospitalized with rhinovirus bronchiolitis have asthma-like characteristics,http://dx.doi.org/10.1016/j.jpeds.2016.01.041,PMC4846467,,,"Children with bronchiolitis often are considered a homogeneous group. However, in a multicenter, prospective study of 2,207 young children hospitalized for bronchiolitis, we found that children with respiratory syncytial virus detected differ from those with rhinovirus detected; the latter patients resemble older children with asthma, including more frequent treatment with corticosteroids.",,"['Mansbach, Jonathan M.', 'Clark, Sunday', 'Teach, Stephen J.', 'Gern, James E.', 'Piedra, Pedro A.', 'Sullivan, Ashley F.', 'Espinola, Janice A.', 'Camargo, Carlos A.']",,,,
,PMC,The Interferon-Stimulated Gene Ifi27l2a Restricts West Nile Virus Infection and Pathogenesis in a Cell-Type- and Region-Specific Manner,http://dx.doi.org/10.1128/JVI.02463-15,PMC4810731,,,"The mammalian host responds to viral infections by inducing expression of hundreds of interferon-stimulated genes (ISGs). While the functional significance of many ISGs has yet to be determined, their cell type and temporal nature of expression suggest unique activities against specific pathogens. Using a combination of ectopic expression and gene silencing approaches in cell culture, we previously identified Ifi27l2a as a candidate antiviral ISG within neuronal subsets of the central nervous system (CNS) that restricts infection by West Nile virus (WNV), an encephalitic flavivirus of global concern. To investigate the physiological relevance of Ifi27l2a in the context of viral infection, we generated Ifi27l2a(−/−) mice. Although adult mice lacking Ifi27l2a were more vulnerable to lethal WNV infection, the viral burden was greater only within the CNS, particularly in the brain stem, cerebellum, and spinal cord. Within neurons of the cerebellum and brain stem, in the context of WNV infection, a deficiency of Ifi27l2a was associated with less cell death, which likely contributed to sustained viral replication and higher titers in these regions. Infection studies in a primary cell culture revealed that Ifi27l2a(−/−) cerebellar granule cell neurons and macrophages but not cerebral cortical neurons, embryonic fibroblasts, or dendritic cells sustained higher levels of WNV infection than wild-type cells and that this difference was greater under conditions of beta interferon (IFN-β) pretreatment. Collectively, these findings suggest that Ifi27l2a has an antiviral phenotype in subsets of cells and that at least some ISGs have specific inhibitory functions in restricted tissues. IMPORTANCE The interferon-stimulated Ifi27l2a gene is expressed differentially within the central nervous system upon interferon stimulation or viral infection. Prior studies in cell culture suggested an antiviral role for Ifi27l2a during infection by West Nile virus (WNV). To characterize its antiviral activity in vivo, we generated mice with a targeted gene deletion of Ifi27l2a. Based on extensive virological analyses, we determined that Ifi27l2a protects mice from WNV-induced mortality by contributing to the control of infection of the hindbrain and spinal cord, possibly by regulating cell death of neurons. This antiviral activity was validated in granule cell neurons derived from the cerebellum and in macrophages but was not observed in other cell types. Collectively, these data suggest that Ifi27l2a contributes to innate immune restriction of WNV in a cell-type- and tissue-specific manner.",,"['Lucas, Tiffany M.', 'Richner, Justin M.', 'Diamond, Michael S.']",,,,
,PMC,Mouse Hepatitis Virus Infection Remodels Connexin43-Mediated Gap Junction Intercellular Communication In Vitro and In Vivo,http://dx.doi.org/10.1128/JVI.02420-15,PMC4810703,,,"Gap junctions (GJs) form intercellular channels which directly connect the cytoplasm between neighboring cells to facilitate the transfer of ions and small molecules. GJs play a major role in the pathogenesis of infection-associated inflammation. Mutations of gap junction proteins, connexins (Cxs), cause dysmyelination and leukoencephalopathy. In multiple sclerosis (MS) patients and its animal model experimental autoimmune encephalitis (EAE), Cx43 was shown to be modulated in the central nervous system (CNS). The mechanism behind Cx43 alteration and its role in MS remains unexplored. Mouse hepatitis virus (MHV) infection-induced demyelination is one of the best-studied experimental animal models for MS. Our studies demonstrated that MHV infection downregulated Cx43 expression at protein and mRNA levels in vitro in primary astrocytes obtained from neonatal mouse brains. After infection, a significant amount of Cx43 was retained in endoplasmic reticulum/endoplasmic reticulum Golgi intermediate complex (ER/ERGIC) and GJ plaque formation was impaired at the cell surface, as evidenced by a reduction of the Triton X-100 insoluble fraction of Cx43. Altered trafficking and impairment of GJ plaque formation may cause the loss of functional channel formation in MHV-infected primary astrocytes, as demonstrated by a reduced number of dye-coupled cells after a scrape-loading Lucifer yellow dye transfer assay. Upon MHV infection, a significant downregulation of Cx43 was observed in the virus-infected mouse brain. This study demonstrates that astrocytic Cx43 expression and function can be modulated due to virus stress and can be an appropriate model to understand the basis of cellular mechanisms involved in the alteration of gap junction intercellular communication (GJIC) in CNS neuroinflammation. IMPORTANCE We found that MHV infection leads to the downregulation of Cx43 in vivo in the CNS. In addition, results show that MHV infection impairs Cx43 expression in addition to gap junction communication in primary astrocytes. After infection, Cx43 did not traffic normally to the membrane to form gap junction plaques, and that could be the basis of reduced functional gap junction coupling between astrocytes. This is an important first step toward understanding how viruses affect Cx43 expression and trafficking at the cellular level. This may provide a basis for understanding how structural alterations of astrocytic gap junctions can disrupt gap junction communication between other CNS cells in altered CNS environments due to infection and inflammation. More specifically, alteration of Cx43 may be the basis of the destabilization of Cx47 in oligodendrocytes seen in and around inflammatory demyelinating plaques in MS patients.",,"['Basu, Rahul', 'Banerjee, Kaveri', 'Bose, Abhishek', 'Das Sarma, Jayasri']",,,,
,PMC,Selective bottlenecks shape evolutionary pathways taken during mammalian adaptation of a 1918-like avian influenza virus,http://dx.doi.org/10.1016/j.chom.2016.01.011,PMC4761429,,,"Avian influenza virus reassortants resembling the 1918 human pandemic virus can become transmissible among mammals by acquiring mutations in hemagglutinin (HA) and polymerase. Using the ferret model, we trace the evolutionary pathway by which an avian-like virus evolves the capacity for mammalian replication and airborne transmission. During initial infection, within-host HA diversity increased drastically. Then, airborne transmission fixed 2 polymerase mutations that do not confer a detectable replication advantage. In later transmissions, selection fixed advantageous HA1 variants. Transmission initially involved a “loose” bottleneck, which became strongly selective after additional HA mutations emerged. The stringency and evolutionary forces governing between-host bottlenecks may therefore change throughout host adaptation. Mutations occurred in multiple combinations in transmitted viruses, suggesting that mammalian transmissibility can evolve through multiple genetic pathways despite phenotypic constraints. Our data provide a glimpse into avian influenza virus adaptation in mammals, with broad implications for surveillance on potentially zoonotic viruses.",,"['Moncla, Louise H.', 'Zhong, Gongxun', 'Nelson, Chase W.', 'Dinis, Jorge M.', 'Mutschler, James', 'Hughes, Austin L.', 'Watanabe, Tokiko', 'Kawaoka, Yoshihiro', 'Friedrich, Thomas C.']",,,,
,PMC,The cGAS-STING Defense Pathway and Its Counteraction by Viruses,http://dx.doi.org/10.1016/j.chom.2016.01.010,PMC4755325,,,"Upon viral infection, host cells mount a concerted innate immune response involving type I interferon and pro-inflammatory cytokines to enable elimination of the pathogen. Recently cGAS and STING have been identified as intracellular sensors that activate the interferon pathway in response to virus infection and thus mediate host defense against a range of DNA and RNA viruses. Here we review how viruses are sensed by the cGAS-STING signaling pathway as well as how viruses modulate this pathway. Mechanisms utilized by viral proteins to inhibit cGAS and/or STING are also discussed. On the flip side, host cells have also evolved strategies to thwart viral immune escape. The balance between host immune control and viral immune evasion is pivotal to viral pathogenesis and we discuss this virus-host stand-off in the context of the cGAS-STING innate immune pathway.",,"['Ma, Zhe', 'Damania, Blossom']",,,,
,PMC,Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice,http://dx.doi.org/10.1016/j.chom.2016.01.007,PMC4752723,,,"Highly pathogenic human respiratory coronaviruses cause acute lethal disease characterized by exuberant inflammatory responses and lung damage. However, the factors leading to lung pathology are not well understood. Using mice infected with SARS (Severe Acute Respiratory Syndrome)-CoV, we show that robust virus replication accompanied by delayed type I interferon (IFN-I) signaling orchestrates inflammatory responses and lung immunopathology with diminished survival. IFN-I remains detectable until after virus titers peak but early IFN-I administration ameliorates immunopathology. This delayed IFN-I signaling promotes the accumulation of pathogenic inflammatory monocyte-macrophages (IMMs), resulting in elevated lung cytokine/chemokine levels, vascular leakage and impaired virus-specific T cell responses. Genetic ablation of the IFN-αβ receptor (IFNAR) or IMM depletion protects mice from lethal infection, without affecting viral load. These results demonstrate that IFN-I and IMM promote lethal SARS-CoV infection and identify IFN-I and IMMs as potential therapeutic targets in patients infected with pathogenic coronavirus and perhaps other respiratory viruses.",,"['Channappanavar, Rudragouda', 'Fehr, Anthony R', 'Vijay, Rahul', 'Mack, Matthias', 'Zhao, Jincun', 'Meyerholz, David K', 'Perlman, Stanley']",,,,
,PMC,Oral immunization of mice with live Pneumocystis murina protects against Pneumocystis pneumonia,http://dx.doi.org/10.4049/jimmunol.1502004,PMC4779750,,,"Pneumocystis pneumonia is a major cause of morbidity and mortality in immunocompromised patients; particularly those infected with human immunodeficiency virus. In this study, we evaluated the potential of oral immunization with live Pneumocystis to elicit protection against respiratory infection with Pneumocystis murina. C57BL/6 mice vaccinated with live P. murina using a prime-boost vaccination strategy were protected from a subsequent lung challenge with P. murina at 2, 7, 14, and 28 days post infection even after CD4+ T cell depletion. Specifically, vaccinated immunocompetent mice had significantly faster clearance than unvaccinated immunocompetent mice and unvaccinated CD4-depleted mice remained persistently infected with P. murina. Vaccination also increased numbers of CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD11b+ macrophages in the lungs following respiratory infection. In addition, levels of lung, serum, and fecal P. murina-specific IgG and IgA were increased in vaccinated animals. Further, administration of serum from vaccinated mice significantly reduced Pneumocystis lung burden in infected animals compared to control serum. We also found that the diversity of the intestinal microbial community was altered by oral immunization with P. murina. Our data demonstrate for the first time that an oral vaccination strategy prevents Pneumocystis infection.",,"['Samuelson, Derrick R.', 'de la Rua, Nicholas M.', 'Charles, Tysheena P.', 'Ruan, Sanbao', 'Taylor, Christopher M.', 'Blanchard, Eugene E.', 'Luo, Meng', 'Ramsay, Alistair J.', 'Shellito, Judd E.', 'Welsh, David A.']",,,,
,PMC,Oxadiazole-Based Cell Permeable Macrocyclic Transition State Inhibitors of Norovirus 3CL Protease,http://dx.doi.org/10.1021/acs.jmedchem.5b01464,PMC5156532,,,"Human noroviruses are the primary causative agents of acute gastroenteritis and a pressing public health burden worldwide. There are currently no vaccines or small molecule therapeutics available for the treatment or prophylaxis of norovirus infections. Norovirus 3CL protease plays a vital role in viral replication by generating structural and nonstructural proteins via the cleavage of the viral polyprotein. Thus, molecules that inhibit the viral protease may have potential therapeutic value. We describe herein the structure-based design, synthesis, and in vitro and cell-based evaluation of the first class of oxadiazole-based, permeable macrocyclic inhibitors of norovirus 3CL protease.",,"['Damalanka, Vishnu C.', 'Kim, Yunjeong', 'Alliston, Kevin R.', 'Weerawarna, Pathum M.', 'Galasiti Kankanamalage, Anushka C.', 'Lushington, Gerald H.', 'Mehzabeen, Nurjahan', 'Battaile, Kevin P.', 'Lovell, Scott', 'Chang, Kyeong-Ok', 'Groutas, William C.']",,,,
,PMC,Activation of RNase L is dependent on OAS3 expression during infection with diverse human viruses,http://dx.doi.org/10.1073/pnas.1519657113,PMC4776461,,,"The 2′,5′-oligoadenylate (2-5A) synthetase (OAS)–RNase L system is an IFN-induced antiviral pathway. RNase L activity depends on 2-5A, synthesized by OAS. Although all three enzymatically active OAS proteins in humans—OAS1, OAS2, and OAS3—synthesize 2-5A upon binding dsRNA, it is unclear which are responsible for RNase L activation during viral infection. We used clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein-9 nuclease (Cas9) technology to engineer human A549-derived cell lines in which each of the OAS genes or RNase L is knocked out. Upon transfection with poly(rI):poly(rC), a synthetic surrogate for viral dsRNA, or infection with each of four viruses from different groups (West Nile virus, Sindbis virus, influenza virus, or vaccinia virus), OAS1-KO and OAS2-KO cells synthesized amounts of 2-5A similar to those synthesized in parental wild-type cells, causing RNase L activation as assessed by rRNA degradation. In contrast, OAS3-KO cells synthesized minimal 2-5A, and rRNA remained intact, similar to infected RNase L-KO cells. All four viruses replicated to higher titers in OAS3-KO or RNase L-KO A549 cells than in parental, OAS1-KO, or OAS2-KO cells, demonstrating the antiviral effects of OAS3. OAS3 displayed a higher affinity for dsRNA in intact cells than either OAS1 or OAS2, consistent with its dominant role in RNase L activation. Finally, the requirement for OAS3 as the major OAS isoform responsible for RNase L activation was not restricted to A549 cells, because OAS3-KO cells derived from two other human cell lines also were deficient in RNase L activation.",,"['Li, Yize', 'Banerjee, Shuvojit', 'Wang, Yuyan', 'Goldstein, Stephen A.', 'Dong, Beihua', 'Gaughan, Christina', 'Silverman, Robert H.', 'Weiss, Susan R.']",,,,
,PMC,Estimating the Severity and Subclinical Burden of Middle East Respiratory Syndrome Coronavirus Infection in the Kingdom of Saudi Arabia,http://dx.doi.org/10.1093/aje/kwv452,PMC4801139,,,"Not all persons infected with Middle East respiratory syndrome coronavirus (MERS-CoV) develop severe symptoms, which likely leads to an underestimation of the number of people infected and an overestimation of the severity. To estimate the number of MERS-CoV infections that have occurred in the Kingdom of Saudi Arabia, we applied a statistical model to a line list describing 721 MERS-CoV infections detected between June 7, 2012, and July 25, 2014. We estimated that 1,528 (95% confidence interval (CI): 1,327, 1,883) MERS-CoV infections occurred in this interval, which is 2.1 (95% CI: 1.8, 2.6) times the number reported. The probability of developing symptoms ranged from 11% (95% CI: 4, 25) in persons under 10 years of age to 88% (95% CI: 72, 97) in those 70 years of age or older. An estimated 22% (95% CI: 18, 25) of those infected with MERS-CoV died. MERS-CoV is deadly, but this work shows that its clinical severity differs markedly between groups and that many cases likely go undiagnosed.",,"['Lessler, Justin', 'Salje, Henrik', 'Van Kerkhove, Maria D.', 'Ferguson, Neil M.', 'Cauchemez, Simon', 'Rodriquez-Barraquer, Isabel', 'Hakeem, Rafat', 'Jombart, Thibaut', 'Aguas, Ricardo', 'Al-Barrak, Ali', 'Cummings, Derek A. T.']",,,,
,PMC,"Legislative smoking bans for reducing harms from secondhand smoke exposure, smoking prevalence and tobacco consumption",http://dx.doi.org/10.1002/14651858.CD005992.pub3,PMC6486282,,,"BACKGROUND: Smoking bans have been implemented in a variety of settings, as well as being part of policy in many jurisdictions to protect the public and employees from the harmful effects of secondhand smoke (SHS). They also offer the potential to influence social norms and the smoking behaviour of those populations they affect. Since the first version of this review in 2010, more countries have introduced national smoking legislation banning indoor smoking. OBJECTIVES: To assess the effects of legislative smoking bans on (1) morbidity and mortality from exposure to secondhand smoke, and (2) smoking prevalence and tobacco consumption. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register, MEDLINE, EMBASE, PsycINFO, CINAHL and reference lists of included studies. We also checked websites of various organisations. Date of most recent search; February 2015. SELECTION CRITERIA: We considered studies that reported legislative smoking bans affecting populations. The minimum standard was having an indoor smoking ban explicitly in the study and a minimum of six months follow‐up for measures of smoking behaviour. Our search included a broad range of research designs including: randomized controlled trials, quasi‐experimental studies (i.e. non‐randomized controlled studies), controlled before‐and‐after studies, interrupted time series as defined by the Cochrane Effective Practice and Organisation of Care Group, and uncontrolled pre‐ and post‐ban data. DATA COLLECTION AND ANALYSIS: One author extracted characteristics and content of the interventions, participants, outcomes and methods of the included studies and a second author checked the details. We extracted health and smoking behaviour outcomes. We did not attempt a meta‐analysis due to the heterogeneity in design and content of the studies included. We evaluated the studies using qualitative narrative synthesis. MAIN RESULTS: There are 77 studies included in this updated review. We retained 12 studies from the original review and identified 65 new studies. Evidence from 21 countries is provided in this update, an increase of eight countries from the original review. The nature of the intervention precludes randomized controlled trials. Thirty‐six studies used an interrupted time series study design, 23 studies use a controlled before‐and‐after design and 18 studies are before‐and‐after studies with no control group; six of these studies use a cohort design. Seventy‐two studies reported health outcomes, including cardiovascular (44), respiratory (21), and perinatal outcomes (7). Eleven studies reported national mortality rates for smoking‐related diseases. A number of the studies report multiple health outcomes. There is consistent evidence of a positive impact of national smoking bans on improving cardiovascular health outcomes, and reducing mortality for associated smoking‐related illnesses. Effects on respiratory and perinatal health were less consistent. We found 24 studies evaluating the impact of national smoke‐free legislation on smoking behaviour. Evidence of an impact of legislative bans on smoking prevalence and tobacco consumption is inconsistent, with some studies not detecting additional long‐term change in existing trends in prevalence. AUTHORS' CONCLUSIONS: Since the first version of this review was published, the current evidence provides more robust support for the previous conclusions that the introduction of a legislative smoking ban does lead to improved health outcomes through reduction in SHS for countries and their populations. The clearest evidence is observed in reduced admissions for acute coronary syndrome. There is evidence of reduced mortality from smoking‐related illnesses at a national level. There is inconsistent evidence of an impact on respiratory and perinatal health outcomes, and on smoking prevalence and tobacco consumption.",,"['Frazer, Kate', 'Callinan, Joanne E', 'McHugh, Jack', 'van Baarsel, Susan', 'Clarke, Anna', 'Doherty, Kirsten', 'Kelleher, Cecily']",,,,
,PMC,Cell Surface Human Airway Trypsin-Like Protease Is Lost During Squamous Cell Carcinogenesis,http://dx.doi.org/10.1002/jcp.25173,PMC4933652,,,"Cancer progression is accompanied by increased levels of extracellular proteases that are capable of remodeling the extracellular matrix, as well as cleaving and activating growth factors and receptors that are involved in pro-cancerous signaling pathways. Several members of the type II transmembrane serine protease (TTSP) family have been shown to play critical roles in cancer progression, however, the expression or function of the TTSP Human Airway Trypsin-like protease (HAT) in carcinogenesis has not been examined. In the present study we aimed to determine the expression of HAT during squamous cell carcinogenesis. HAT transcript is present in several tissues containing stratified squamous epithelium and decreased expression is observed in carcinomas. We determined that HAT protein is consistently expressed on the cell surface in suprabasal/apical layers of squamous cells in healthy cervical and esophageal epithelia. To assess whether HAT protein is differentially expressed in normal tissue versus tissue in different stages of carcinogenesis, we performed a comprehensive immunohistochemical analysis of HAT protein expression levels and localization in arrays of paraffin embedded human cervical and esophageal carcinomas compared to the corresponding normal tissue. We found that HAT protein is expressed in the non-proliferating, differentiated cellular strata and is lost during the dedifferentiation of epithelial cells, a hallmark of squamous cell carcinogenesis. Thus, HAT expression may potentially be useful as a marker for clinical grading and assessment of patient prognosis in squamous cell carcinomas.",,"['DUHAIME, MICHAEL J.', 'PAGE, KHALIPH O.', 'VARELA, FAUSTO A.', 'MURRAY, ANDREW S.', 'SILVERMAN, MICHAEL E.', 'ZORATTI, GINA L.', 'LIST, KARIN']",,,,
,PMC,Corticosteroids for severe influenza pneumonia: A critical appraisal,http://dx.doi.org/10.5492/wjccm.v5.i1.89,PMC4733461,,,"Influenza pneumonia is associated with high number of severe cases requiring hospital and intensive care unit (ICU) admissions with high mortality. Systemic steroids are proposed as a valid therapeutic option even though its effects are still controversial. Heterogeneity of published data regarding study design, population demographics, severity of illness, dosing, type and timing of corticosteroids administered constitute an important limitation for drawing robust conclusions. However, it is reasonable to admit that, as it was not found any advantage of corticosteroid therapy in so diverse conditions, such beneficial effects do not exist at all. Its administration is likely to increase overall mortality and such trend is consistent regardless of the quality as well as the sample size of studies. Moreover it was shown that corticosteroids might be associated with higher incidence of hospital-acquired pneumonia and longer duration of mechanical ventilation and ICU stay. Finally, it is reasonable to conclude that corticosteroids failed to demonstrate any beneficial effects in the treatment of patients with severe influenza infection. Thus its current use in severe influenza pneumonia should be restricted to very selected cases and in the setting of clinical trials.",,"['Nedel, Wagner Luis', 'Nora, David Garcia', 'Salluh, Jorge Ibrain Figueira', 'Lisboa, Thiago', 'Póvoa, Pedro']",,,,
,PMC,pMINERVA: A Donor-Acceptor System for the in vivo Recombineering of scFv into IgG Molecules,http://dx.doi.org/10.1016/j.jim.2016.02.003,PMC4792691,,,"Phage display is the most widely used method for selecting binding molecules from recombinant antibody libraries. However, validation of the phage antibodies often requires early production of the cognate full-length immunoglobulin G (IgG). The conversion of phage library outputs to a full immunoglobulin via standard subcloning is time-consuming and limits the number of clones that can be evaluated. We have developed a novel system to convert scFvs from a phage display vector directly into IgGs without any in vitro subcloning steps. This new vector system, named pMINERVA, makes clever use of site-specific bacteriophage integrases that are expressed in E. coli and intron splicing that occurs within mammalian cells. Using this system, a phage display vector contains both bacterial and mammalian regulatory regions that support antibody expression in E. coli and mammalian cells. A single-chain variable fragment (scFv) antibody is expressed on the surface of bacteriophage M13 as a genetic fusion to the gpIII coat protein. The scFv is converted to an IgG that can be expressed in mammalian cells by transducing a second E. coli strain. In that strain, the phiC31 recombinase fuses the heavy chain constant domain from an acceptor plasmid to the heavy chain variable domain and introduces controlling elements upstream of the light chain variable domain. Splicing in mammalian cells removes a synthetic intron containing the M13 gpIII gene to produce the fusion of the light chain variable domain to the constant domain. We show that phage displaying a scFv and recombinant IgGs generated using this system are expressed at wild-type levels and retain normal function. Use of the pMINERVA completely eliminates the labor-intensive subcloning and DNA sequence confirmation steps currently needed to convert a scFv into a functional IgG Ab.",,"['Batonick, M', 'Kiss, MM', 'Fuller, EP', 'Magadan, CM', 'Holland, EG', 'Zhao, Q', 'Wang, D', 'Kay, BK', 'Weiner, MP']",,,,
,PMC,Principles Governing the Self-Assembly of Coiled-Coil Protein Nanoparticles,http://dx.doi.org/10.1016/j.bpj.2015.10.057,PMC4744166,,,"Self-assembly refers to the spontaneous organization of individual building blocks into higher order structures. It occurs in biological systems such as spherical viruses, which utilize icosahedral symmetry as a guiding principle for the assembly of coat proteins into a capsid shell. In this study, we characterize the self-assembling protein nanoparticle (SAPN) system, which was inspired by such viruses. To facilitate self-assembly, monomeric building blocks have been designed to contain two oligomerization domains. An N-terminal pentameric coiled-coil domain is linked to a C-terminal coiled-coil trimer by two glycine residues. By combining monomers with inherent propensity to form five- and threefold symmetries in higher order agglomerates, the supposition is that nanoparticles will form that exhibit local and global symmetry axes of order 3 and 5. This article explores the principles that govern the assembly of such a system. Specifically, we show that the system predominantly forms according to a spherical core-shell morphology using a combination of scanning transmission electron microscopy and small angle neutron scattering. We introduce a mathematical toolkit to provide a specific description of the possible SAPN morphologies, and we apply it to characterize all particles with maximal symmetry. In particular, we present schematics that define the relative positions of all individual chains in the symmetric SAPN particles, and provide a guide of how this approach can be generalized to nonspherical morphologies, hence providing unprecedented insights into their geometries that can be exploited in future applications.",,"['Indelicato, Giuliana', 'Wahome, Newton', 'Ringler, Philippe', 'Müller, Shirley\xa0A.', 'Nieh, Mu-Ping', 'Burkhard, Peter', 'Twarock, Reidun']",,,,
,PMC,"Expression and purification of an engineered, yeast-expressed Leishmania donovani nucleoside hydrolase with immunogenic properties",http://dx.doi.org/10.1080/21645515.2016.1139254,PMC4964838,,,"Leishmania donovani is the major cause of visceral leishmaniasis (kala-azar), now recognized as the parasitic disease with the highest level of mortality second only to malaria. No human vaccine is currently available. A 36 kDa L. donovani nucleoside hydrolase (LdNH36) surface protein has been previously identified as a potential vaccine candidate antigen. Here we present data on the expression of LdNH36 in Pichia pastoris and its purification at the 20 L scale to establish suitability for future pilot scale manufacturing. To improve efficiency of process development and ensure reproducibility, 4 N-linked glycosylation sites shown to contribute to heterogeneous high-mannose glycosylation were mutated to glutamine residues. The mutant LdNH36 (LdNH36-dg2) was expressed and purified to homogeneity. Size exclusion chromatography and light scattering demonstrated that LdNH36-dg2 existed as a tetramer in solution, similar to the wild-type recombinant L. major nucleoside hydrolase. The amino acid mutations do not affect the tetrameric interface as confirmed by theoretical modeling, and the mutated amino acids are located outside the major immunogenic domain. Immunogenic properties of the LdNH36-dg2 recombinant protein were evaluated in BALB/c mice using formulations that included a synthetic CpG oligodeoxynucleotide, together with a microparticle delivery platform (poly(lactic-co-glycolic acid)). Mice exhibited high levels of IgG1, IgG2a, and IgG2b antibodies that were reactive to both LdNH36-dg2 and LdNH36 wild-type. While the point mutations did affect the hydrolase activity of the enzyme, the IgG antibodies elicited by LdNH36-dg2 were shown to inhibit the hydrolase activity of the wild-type LdNH36. The results indicate that LdNH36-dg2 as expressed in and purified from P. pastoris is suitable for further scale-up, manufacturing, and testing in support of future first-in-humans phase 1 clinical trials.",,"['Hudspeth, Elissa M.', 'Wang, Qian', 'Seid, Christopher A.', 'Hammond, Molly', 'Wei, Junfei', 'Liu, Zhuyun', 'Zhan, Bin', 'Pollet, Jeroen', 'Heffernan, Michael J.', 'McAtee, C. Patrick', 'Engler, David A.', 'Matsunami, Risë K.', 'Strych, Ulrich', 'Asojo, Oluwatoyin A.', 'Hotez, Peter J.', 'Bottazzi, Maria Elena']",,,,
,PMC,Disaster Preparedness: Need for inclusion in undergraduate nursing education,http://dx.doi.org/10.18295/squmj.2016.16.01.004,PMC4746037,,,"With the increasing global frequency of disasters, the call for disaster preparedness training needs to be reinforced. Nurses form the largest group of the healthcare workforce and are often on the frontline in disaster management. Therefore, nurses should be adequately equipped with the knowledge and skills to respond to disasters, starting from their pre-service training to their in-service professional training. However, the inclusion of disaster preparedness education in undergraduate nursing curricula is minimal in most countries. The purpose of this article is to highlight the current state of nursing education and training in disaster management, both generally and in Oman. The significance of disaster preparedness training and recommendations for its inclusion in nursing practice and education are also discussed.",,"['Achora, Susan', 'Kamanyire, Joy K.']",,,,
,PMC,Associating Changes in the Immune System with Clinical Diseases for Interpretation in Risk Assessment,http://dx.doi.org/10.1002/0471140856.tx1801s67,PMC4780336,,,"This overview is an update of the unit originally published in 2004. While the basic tenants of immunotoxicity have not changed in the past 10 years, several publications have explored the application of immunotoxicological data to the risk assessment process. Therefore, the goal of this unit is still to highlight relationships between xenobiotic-induced immunosuppression and risk of clinical diseases progression. In immunotoxicology, this may require development of models to equate moderate changes in markers of immune functions to potential changes in incidence or severity of infectious diseases. For most xenobiotics, exposure levels and disease incidence data are rarely available and safe exposure levels must be estimated based on observations from experimental models or human biomarker studies. Thus, it is important to establish a scientifically sound framework that allows accurate and quantitative interpretation of experimental or biomarker data in the risk assessment process.",,"['DeWitt, Jamie C.', 'Germolec, Dori R.', 'Luebke, Robert W.', 'Johnson, Victor J.']",,,,
,PMC,A generalized-growth model to characterize the early ascending phase of infectious disease outbreaks,http://dx.doi.org/10.1016/j.epidem.2016.01.002,PMC4903879,,,"BACKGROUND: A better characterization of the early growth dynamics of an epidemic is needed to dissect the important drivers of disease transmission, refine existing transmission models, and improve disease forecasts. MATERIALS AND METHODS: We introduce a 2-parameter generalized-growth model to characterize the ascending phase of an outbreak and capture epidemic profiles ranging from sub-exponential to exponential growth. We test the model against empirical outbreak data representing a variety of viral pathogens in historic and contemporary populations, and provide simulations highlighting the importance of sub-exponential growth for forecasting purposes. RESULTS: We applied the generalized-growth model to 20 infectious disease outbreaks representing a range of transmission routes. We uncovered epidemic profiles ranging from very slow growth (p=0.14 for the Ebola outbreak in Bomi, Liberia (2014)) to near exponential (p>0.9 for the smallpox outbreak in Khulna (1972), and the 1918 pandemic influenza in San Francisco). The foot-and-mouth disease outbreak in Uruguay displayed a profile of slower growth while the growth pattern of the HIV/AIDS epidemic in Japan was approximately linear. The West African Ebola epidemic provided a unique opportunity to explore how growth profiles vary by geography; analysis of the largest district-level outbreaks revealed substantial growth variations (mean p=0.59, range: 0.14–0.97). The districts of Margibi in Liberia and Bombali and Bo in Sierra Leone had near-exponential growth, while the districts of Bomi in Liberia and Kenema in Sierra Leone displayed near constant incidences. CONCLUSIONS: Our findings reveal significant variation in epidemic growth patterns across different infectious disease outbreaks and highlights that sub-exponential growth is a common phenomenon, especially for pathogens that are not airborne. Sub-exponential growth profiles may result from heterogeneity in contact structures or risk groups, reactive behavior changes, or the early onset of interventions strategies, and consideration of “deceleration parameters” may be useful to refine existing mathematical transmission models and improve disease forecasts.",,"['Viboud, Cécile', 'Simonsen, Lone', 'Chowell, Gerardo']",,,,
,PMC,Middle East respiratory syndrome: A new global threat,http://dx.doi.org/10.4103/0019-5049.176286,PMC4787138,27013745,CC BY-NC-SA,"The outbreak of Middle East respiratory syndrome (MERS) is reported from Saudi Arabia and the Republic of Korea. It is a respiratory disease caused by coronavirus. Camels are considered as a source for MERS transmission in humans, although the exact source is unknown. Human-to-human transmission is reported in the community with droplet and contact spread being the possible modes. Most patients without any underlying diseases remain asymptomatic or develop mild clinical disease, but some patients require critical care for mechanical ventilation, dialysis and other organ support. MERS is a disease with pandemic potential and awareness, and surveillance can prevent such further outbreaks.",2016 Feb,"['Bhatia, Pradeep Kumar', 'Sethi, Priyanka', 'Gupta, Neeraj', 'Biyani, Ghansham']",Indian J Anaesth,,,
,PMC,Necessary Infrastructure of Infection Prevention and Healthcare Epidemiology Programs: A Review,http://dx.doi.org/10.1017/ice.2015.333,PMC6481289,,,,,"['Bryant, Kristina A.', 'Harris, Anthony D.', 'Gould, Carolyn V.', 'Humphreys, Eve', 'Lundstrom, Tammy', 'Murphy, Denise M.', 'Olmsted, Russell', 'Oriola, Shannon', 'Zerr, Danielle']",,,,
,PMC,Endoplasmic Reticulum Stress Interacts With Inflammation in Human Diseases,http://dx.doi.org/10.1002/jcp.25098,PMC4659393,,,"The endoplasmic reticulum is a critical organelle for normal cell function and homeostasis. Disturbed protein folding process in the ER, termed ER stress, leads to the activation of unfolded protein response (UPR) that encompasses a complex network of intracellular signaling pathways. The UPR can either restore ER homeostasis or activate pro-apoptotic pathways depending on specific insults, intensity and duration of the stress, and cell types. ER stress and the UPR have recently been linked to inflammation in a variety of human pathologies including autoimmune diseases, infection, neurodegenerative disease, and metabolic disorders. In the cell, ER stress and inflammatory signaling share extensive regulators and effectors in a broad spectrum of biological processes. In spite of different etiologies, the two signaling pathways were shown to form a vicious cycle in exacerbating cellular dysfunction and causing apoptosis in many cells and tissues. However, the interaction between ER stress and inflammation in many of these diseases remains elusive. Further understanding of those issues may enable the development of novel therapies that spontaneously target these pathogenic pathways.",,"['Cao, Stewart Siyan', 'Luo, Katherine L.', 'Shi, Lynn']",,,,
,PMC,Middle East respiratory syndrome coronavirus shows poor replication but significant induction of antiviral responses in human monocyte-derived macrophages and dendritic cells,http://dx.doi.org/10.1099/jgv.0.000351,PMC4804640,,,"In this study we assessed the ability of Middle East respiratory syndrome coronavirus (MERS-CoV) to replicate and induce innate immunity in human monocyte-derived macrophages and dendritic cells (MDDCs), and compared it with severe acute respiratory syndrome coronavirus (SARS-CoV). Assessments of viral protein and RNA levels in infected cells showed that both viruses were impaired in their ability to replicate in these cells. Some induction of IFN-λ1, CXCL10 and MxA mRNAs in both macrophages and MDDCs was seen in response to MERS-CoV infection, but almost no such induction was observed in response to SARS-CoV infection. ELISA and Western blot assays showed clear production of CXCL10 and MxA in MERS-CoV-infected macrophages and MDDCs. Our data suggest that SARS-CoV and MERS-CoV replicate poorly in human macrophages and MDDCs, but MERS-CoV is nonetheless capable of inducing a readily detectable host innate immune response. Our results highlight a clear difference between the viruses in activating host innate immune responses in macrophages and MDDCs, which may contribute to the pathogenesis of infection.",,"['Tynell, Janne', 'Westenius, Veera', 'Rönkkö, Esa', 'Munster, Vincent J.', 'Melén, Krister', 'Österlund, Pamela', 'Julkunen, Ilkka']",,,,
,PMC,Engaging the international community during the 2015 Middle East respiratory syndrome outbreak in the Republic of Korea,http://dx.doi.org/10.5365/WPSAR.2015.6.4.003,PMC5052893,,,,,"['Lee, Minwon', 'Nam, Hoohee', 'Lee, Sun-Gyu', 'Park, Ok', 'Jee, Youngmee', 'Park, Kidong']",,,,
,PMC,"Group X Secreted Phospholipase A(2) Releases ω3 Polyunsaturated Fatty Acids, Suppresses Colitis, and Promotes Sperm Fertility",http://dx.doi.org/10.1074/jbc.M116.715672,PMC4807275,,,"Within the secreted phospholipase A(2) (sPLA(2)) family, group X sPLA(2) (sPLA(2)-X) has the highest capacity to hydrolyze cellular membranes and has long been thought to promote inflammation by releasing arachidonic acid, a precursor of pro-inflammatory eicosanoids. Unexpectedly, we found that transgenic mice globally overexpressing human sPLA(2)-X (PLA2G10-Tg) displayed striking immunosuppressive and lean phenotypes with lymphopenia and increased M2-like macrophages, accompanied by marked elevation of free ω3 polyunsaturated fatty acids (PUFAs) and their metabolites. Studies using Pla2g10-deficient mice revealed that endogenous sPLA(2)-X, which is highly expressed in the colon epithelium and spermatozoa, mobilized ω3 PUFAs or their metabolites to protect against dextran sulfate-induced colitis and to promote fertilization, respectively. In colitis, sPLA(2)-X deficiency increased colorectal expression of Th17 cytokines, and ω3 PUFAs attenuated their production by lamina propria cells partly through the fatty acid receptor GPR120. In comparison, cytosolic phospholipase A(2) (cPLA(2)α) protects from colitis by mobilizing ω6 arachidonic acid metabolites, including prostaglandin E(2). Thus, our results underscore a previously unrecognized role of sPLA(2)-X as an ω3 PUFA mobilizer in vivo, segregated mobilization of ω3 and ω6 PUFA metabolites by sPLA(2)-X and cPLA(2)α, respectively, in protection against colitis, and the novel role of a particular sPLA(2)-X-driven PUFA in fertilization.",,"['Murase, Remi', 'Sato, Hiroyasu', 'Yamamoto, Kei', 'Ushida, Ayako', 'Nishito, Yasumasa', 'Ikeda, Kazutaka', 'Kobayashi, Tetsuyuki', 'Yamamoto, Toshinori', 'Taketomi, Yoshitaka', 'Murakami, Makoto']",,,,
,PMC,"3B11-N, a Monoclonal Antibody Against MERS-CoV, Reduces Lung Pathology in Rhesus Monkeys following Intratracheal Inoculation of MERS-CoV Jordan-n3/2012",http://dx.doi.org/10.1016/j.virol.2016.01.004,PMC4769911,,,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was identified in 2012 as the causative agent of a severe, lethal respiratory disease occurring across several countries in the Middle East. To date there have been over 1,600 laboratory confirmed cases of MERS-CoV in 26 countries with a case fatality rate of 36%. Given the endemic region, it is possible that MERS-CoV could spread during the annual Hajj pilgrimage, necessitating countermeasure development. In this report, we describe the clinical and radiographic changes of rhesus monkeys following infection with 5×10(6) PFU MERS-CoV Jordan-n3/2012. Two groups of NHPs were treated with either a human anti-MERS monoclonal antibody 3B11-N or E410-N, an anti-HIV antibody. MERS-CoV Jordan-n3/2012 infection resulted in quantifiable changes by computed tomography, but limited other clinical signs of disease. 3B11-N treated subjects developed significantly reduced lung pathology when compared to infected, untreated subjects, indicating that this antibody may be a suitable MERS-CoV treatment.",,"['Johnson, Reed F.', 'Bagci, Ulas', 'Keith, Lauren', 'Tang, Xianchun', 'Mollura, Daniel J.', 'Zeitlin, Larry', 'Qin, Jing', 'Huzella, Louis', 'Bartos, Christopher J.', 'Bohorova, Natasha', 'Bohorov, Ognian', 'Goodman, Charles', 'Kim, Do H.', 'Paulty, Michael H.', 'Velasco, Jesus', 'Whaley, Kevin J.', 'Johnson, Joshua C.', 'Pettitt, James', 'Ork, Britini L.', 'Solomon, Jeffrey', 'Oberlander, Nicholas', 'Zhu, Quan', 'Sun, Jiusong', 'Holbrook, Michael R.', 'Olinger, Gene G.', 'Baric, Ralph S.', 'Hensley, Lisa E.', 'Jahrling, Peter B.', 'Marasco, Wayne A.']",,,,
,PMC,A Conserved Inhibitory Mechanism of a Lycorine Derivative against Enterovirus and Hepatitis C Virus,http://dx.doi.org/10.1128/AAC.02274-15,PMC4750679,,,"Enterovirus 71 (EV71) (Picornaviridae family) and hepatitis C virus (HCV) (Flaviviridae family) are the causative agents of human hand, foot, and mouth disease (HFMD) and hepatitis C, resulting in a severe pandemic involving millions of infections in the Asia-Pacific region and worldwide. The great impact of EV71 and HCV on public health highlights the need to further our understanding of the biology of these two viruses and develop effective therapeutic antivirals. Here, we evaluated a total of 32 lycorine derivatives and demonstrated that 1-acetyllycorine suppressed the proliferation of multiple strains of EV71 in various cells. The results of the drug resistance analysis revealed that 1-acetyllycorine targeted a phenylalanine (F76) in EV71 2A protease (2A(pro)) to stabilize the conformation of a unique zinc finger. Most interestingly, the zinc binding site in EV71 2A(pro) is the exclusive homolog of HCV NS3 among all viruses. Further analysis revealed that 1-acetyllycorine also inhibits HCV with high efficacy, and the mutation on R118 in HCV NS3, which corresponds to F76 in EV71 2A(pro), confers the resistance of HCV to 1-acetyllycorine. These results revealed a conserved mechanism of 1-acetyllycorine against EV71 and HCV through targeting viral proteases. We also documented the significant synergistic anti-EV71 and anti-HCV effects of 1-acetyllycorine with reported inhibitors, supporting potential combination therapy for the treatment of EV71 and HCV infections.",,"['Guo, Yu', 'Wang, Yaxin', 'Cao, Lin', 'Wang, Peng', 'Qing, Jie', 'Zheng, Qizhen', 'Shang, Luqing', 'Yin, Zheng', 'Sun, Yuna']",,,,
,PMC,Conservation as vaccination: Integrated approaches to public health and environmental protection could prevent future disease outbreaks,http://dx.doi.org/10.15252/embr.201541675,PMC4772977,,,"The main lesson from the 2015 Ebola outbreak is that we need to increase global preparedness to better deal with zoonotic disease outbreaks. Yet, it might be a more efficient strategy to prevent such zoonotic spillover events in the first place through conservation measures to protect biodiversity and wildlife. [Image: see text]",,"Hayman, David TS",,,,
,PMC,Efficacy of an automated multi-emitter whole room UV-C disinfection system against Coronaviruses MHV and MERS-CoV,http://dx.doi.org/10.1017/ice.2015.348,PMC5369231,,,"The virus responsible for Middle Eastern respiratory syndrome, MERS-CoV is a lineage C betacoronavirus similar to the mouse hepatitis virus type A59 (MHV-A59). The first reported case of MERS occurred in Saudi Arabia in 2012 and resulted in 76 deaths(1). Outbreaks of MERS have since occurred not only in the Middle East but South Korea as well(2). Rapid, efficient, and automated methods of disinfecting surfaces contaminated with the MERS-CoV virus may prevent the spread of the virus in the healthcare setting. Here we report on the use of an automated triple-emitter whole room disinfection system to inactivate the MHV-A59 and the MERS-CoV viruses on surfaces with a greater than 5 log(10) reduction on MERS in 5 minutes of UV-C exposure.",,"['Bedell, Kurt', 'Buchaklian, Adam', 'Perlman, Stanley']",,,,
,PMC,Crystal Structure of Feline Infectious Peritonitis Virus Main Protease in Complex with Synergetic Dual Inhibitors,http://dx.doi.org/10.1128/JVI.02685-15,PMC4734010,,,"Coronaviruses (CoVs) can cause highly prevalent diseases in humans and animals. Feline infectious peritonitis virus (FIPV) belongs to the genus Alphacoronavirus, resulting in a lethal systemic granulomatous disease called feline infectious peritonitis (FIP), which is one of the most important fatal infectious diseases of cats worldwide. No specific vaccines or drugs have been approved to treat FIP. CoV main proteases (M(pro)s) play a pivotal role in viral transcription and replication, making them an ideal target for drug development. Here, we report the crystal structure of FIPV M(pro) in complex with dual inhibitors, a zinc ion and a Michael acceptor. The complex structure elaborates a unique mechanism of two distinct inhibitors synergizing to inactivate the protease, providing a structural basis to design novel antivirals and suggesting the potential to take advantage of zinc as an adjunct therapy against CoV-associated diseases. IMPORTANCE Coronaviruses (CoVs) have the largest genome size among all RNA viruses. CoV infection causes various diseases in humans and animals, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). No approved specific drugs or vaccinations are available to treat their infections. Here, we report a novel dual inhibition mechanism targeting CoV main protease (M(pro)) from feline infectious peritonitis virus (FIPV), which leads to lethal systemic granulomatous disease in cats. M(pro), conserved across all CoV genomes, is essential for viral replication and transcription. We demonstrated that zinc ion and a Michael acceptor-based peptidomimetic inhibitor synergistically inactivate FIPV M(pro). We also solved the structure of FIPV M(pro) complexed with two inhibitors, delineating the structural view of a dual inhibition mechanism. Our study provides new insight into the pharmaceutical strategy against CoV M(pro) through using zinc as an adjuvant therapy to enhance the efficacy of an irreversible peptidomimetic inhibitor.",,"['Wang, Fenghua', 'Chen, Cheng', 'Liu, Xuemeng', 'Yang, Kailin', 'Xu, Xiaoling', 'Yang, Haitao']",,,,
,PMC,Porcine Epidemic Diarrhea Virus 3C-Like Protease Regulates Its Interferon Antagonism by Cleaving NEMO,http://dx.doi.org/10.1128/JVI.02514-15,PMC4733996,,,"Porcine epidemic diarrhea virus (PEDV) is an enteropathogenic coronavirus causing lethal watery diarrhea in piglets. Since 2010, a PEDV variant has spread rapidly in China, and it emerged in the United States in 2013, posing significant economic and public health concerns. The ability to circumvent the interferon (IFN) antiviral response, as suggested for PEDV, promotes viral survival and regulates pathogenesis of PEDV infections, but the underlying mechanisms remain obscure. Here, we show that PEDV-encoded 3C-like protease, nsp5, is an IFN antagonist that proteolytically cleaves the nuclear transcription factor kappa B (NF-κB) essential modulator (NEMO), an essential adaptor bridging interferon-regulatory factor and NF-κB activation. NEMO is cleaved at glutamine 231 (Q231) by PEDV, and this cleavage impaired the ability of NEMO to activate downstream IFN production and to act as a signaling adaptor of the RIG-I/MDA5 pathway. Mutations specifically disrupting the cysteine protease activity of PEDV nsp5 abrogated NEMO cleavage and the inhibition of IFN induction. Structural analysis suggests that several key residues outside the catalytic sites of PEDV nsp5 probably impact NEMO cleavage by modulating potential interactions of nsp5 with their substrates. These data show that PEDV nsp5 disrupts type I IFN signaling by cleaving NEMO. Previously, we and others demonstrated that NEMO is also cleaved by 3C or 3C-like proteinases of picornavirus and artertivirus. Thus, NEMO probably represents a prime target for 3C or 3C-like proteinases of different viruses. IMPORTANCE The continued emergence and reemergence of porcine epidemic diarrhea virus (PEDV) underscore the importance of studying how this virus manipulates the immune responses of its hosts. During coevolution with its hosts, PEDV has acquired mechanisms to subvert host innate immune responses for its survival advantage. At least two proteins encoded by PEDV have been identified as interferon (IFN) antagonists, papain-like protease (PLP) and N protein. Here, we report that the PEDV nsp5 gene, which encodes the 3C-like protease of PEDV, is another IFN antagonist. Mechanistically, the cysteine protease activity of PEDV nsp5 mediates proteolysis of NEMO, the key adaptor for IFN synthesis, and NEMO is cleaved at glutamine 231 (Q231). The new molecular details and determinants impacting NEMO scission by PEDV nsp5 delineated in this study are fundamental to our understanding of critical virus-host interactions that determine PEDV pathogenesis.",,"['Wang, Dang', 'Fang, Liurong', 'Shi, Yanling', 'Zhang, Huan', 'Gao, Li', 'Peng, Guiqing', 'Chen, Huanchun', 'Li, Kui', 'Xiao, Shaobo']",,,,
,PMC,Host restriction factors for hepatitis C virus,http://dx.doi.org/10.3748/wjg.v22.i4.1477,PMC4721981,,,"Host-hepatitis C virus (HCV) interactions have both informed fundamental concepts of viral replication and pathogenesis and provided novel insights into host cell biology. These findings are illustrated by the recent discovery of host-encoded factors that restrict HCV infection. In this review, we briefly discuss these restriction factors in different steps of HCV infection. In each case, we discuss how these restriction factors were identified, the mechanisms by which they inhibit HCV infection and their potential contribution to viral pathogenesis.",,"['Zhou, Li-Ya', 'Zhang, Lei-Liang']",,,,
,PMC,Exploration of the effects of classroom humidity levels on teachers’ respiratory symptoms,http://dx.doi.org/10.1007/s00420-016-1111-0,PMC4873430,,,"PURPOSE: Previous studies indicate that teachers have higher asthma prevalence than other non-industrial worker groups. Schools frequently have trouble maintaining indoor relative humidity (RH) within the optimum range (30-50%) for reducing allergens and irritants. However, the potential relationship between classroom humidity and teachers’ health has not been explored. Thus, we examined the relationship between classroom humidity levels and respiratory symptoms among North Carolina teachers. METHODS: Teachers (n=122) recorded daily symptoms, while data-logging hygrometers recorded classroom RH levels in 10 North Carolina schools. We examined effects of indoor humidity on occurrence of symptoms using modified Poisson regression models for correlated binary data. RESULTS: The risk of asthma-like symptoms among teachers with classroom RH >50% for five days was 1.27 (0.81, 2.00) times the risk among the referent [teachers with classroom RH 30-50%]. The risk of cold/ allergy symptoms among teachers with classroom RH >50% for five days was 1.06 (0.82, 1.37) times the risk among the referent. Low RH (<30%) for five days, was associated with increased risk of asthma-like [Risk Ratio (RR): 1.26 (0.73, 2.17)] and cold/allergy symptoms [RR: 1.11 (0.90, 1.37)]. CONCLUSIONS: Our findings suggest that prolonged exposure to high or low classroom RH was associated with modest (but not statistically significant) increases in the risk of respiratory symptoms among teachers.",,"['Angelon-Gaetz, Kim A.', 'Richardson, David B.', 'Marshall, Stephen W.', 'Hernandez, Michelle L.']",,,,
,PMC,"Tamara Giles-Vernick, L. A. James, and J. R. Webb, eds. Global Health in Africa: Historical Perspectives on Disease Control Ruth J. Prince and Rebecca Marsland, eds. Making and Unmaking Public Health in Africa: Ethnographic and Historical Perspectives Wenzel Geissler, ed. Para-States and Medical Science: Making African Global Health",http://dx.doi.org/10.1093/jhmas/jrv056,PMC4986215,,,,,"Ngalamulume, Kalala",,,,
,PMC,"Microfluidic assay for precise measurements of mouse, rat, and human neutrophil chemotaxis in whole‐blood droplets",http://dx.doi.org/10.1189/jlb.5TA0715-310RR,PMC6608085,,,"Animal models of human disease differ in innate immune responses to stress, pathogens, or injury. Precise neutrophil phenotype measurements could facilitate interspecies comparisons. However, such phenotype comparisons could not be performed accurately with the use of current assays, as they require the separation of neutrophils from blood using species‐specific protocols, and they introduce distinct artifacts. Here, we report a microfluidic technology that enables robust characterization of neutrophil migratory phenotypes in a manner independent of the donor species and performed directly in a droplet of whole blood. The assay relies on the particular ability of neutrophils to deform actively during chemotaxis through microscale channels that block the advance of other blood cells. Neutrophil migration is measured directly in blood, in the presence of other blood cells and serum factors. Our measurements reveal important differences among migration counts, velocity, and directionality among neutrophils from 2 common mouse strains, rats, and humans.",,"['Jones, Caroline N.', 'Hoang, Anh N.', 'Martel, Joseph M.', 'Dimisko, Laurie', 'Mikkola, Amy', 'Inoue, Yoshitaka', 'Kuriyama, Naohide', 'Yamada, Marina', 'Hamza, Bashar', 'Kaneki, Masao', 'Warren, H. Shaw', 'Brown, Diane E.', 'Irimia, Daniel']",,,,
,PMC,Successful therapeutic management of canine Isosporosis in puppies,http://dx.doi.org/10.1007/s12639-015-0747-0,PMC5339170,,,"Four labrador male puppies were confirmed for the Isospora spp infection by direct smear and flotation method following complains of anorexia, haematemesis and haematochezia. The puppies were treated with trimethoprime and sulphamethoxazole @ 40 mg/kg body weight in combination with metronidazole @ 10 mg/kg body weight twice daily for 5 days which was supported with fluid therapy, aniemetics and plasma expanders. All the animals showed completed clinical recovery along with clearing of faecal oocyst.",,"['Garanayak, Nishiswapna', 'Gupta, A. R.', 'Patra, R. C.']",,,,
,PMC,A new oxygen modification cyclooctaoxygen binds to nucleic acids as sodium crown complex,http://dx.doi.org/10.1016/j.bbagen.2016.01.022,PMC4780752,,,"BACKGROUND: Oxygen exists in two gaseous and six solid allotropic modifications. An additional allotropic modification of oxygen, the cyclooctaoxygen, was predicted to exist in 1990. METHODS: Cyclooctaoxygen sodium was synthesized in vitro from atmospheric oxygen, or catalase effect-generated oxygen, under catalysis of cytosine nucleosides and either ninhydrin or eukaryotic low-molecular weight RNA. Thin-layer chromatographic mobility shift assays were applied on specific nucleic acids and the cyclooctaoxygen sodium complex. RESULTS: We report the first synthesis and characterization of cyclooctaoxygen as its sodium crown complex, isolated in the form of three cytosine nucleoside hydrochloride complexes. The cationic cyclooctaoxygen sodium complex is shown to bind to nucleic acids (RNA and DNA), to associate with single-stranded DNA and spermine phosphate, and to be essentially non-toxic to cultured mammalian cells at 0.1–1.0 mM concentration. CONCLUSIONS: We postulate that cyclooctaoxygen is formed in most eukaryotic cells in vivo from dihydrogen peroxide in a catalase reaction catalyzed by cytidine and RNA. A molecular biological model is deduced for a first epigenetic shell of eukaryotic in vivo DNA. This model incorporates an epigenetic explanation for the interactions of the essential micronutrient selenium (as selenite) with eukaryotic in vivo DNA. GENERAL SIGNIFICANCE: Since the sperminium phosphate/cyclooctaoxygen sodium complex is calculated to cover the active regions (2.6%) of bovine lymphocyte interphase genome, and 12.4% of murine enterocyte mitotic chromatin, we propose that the sperminium phosphate/cyclooctaoxygen sodium complex coverage of nucleic acids is essential to eukaryotic gene regulation and promoted proto-eukaryotic evolution.",,"['Kesel, Andreas J.', 'Day, Craig W.', 'Montero, Catherine M.', 'Schinazi, Raymond F.']",,,,
,PMC,Type I interferons in viral control and immune regulation,http://dx.doi.org/10.1016/j.coviro.2016.01.001,PMC4821698,,,"Type 1 interferons (IFN-I) exert pleiotropic biological effects during viral infections, all which contribute to balancing virus control and immune pathology. Despite extensive antiviral functions that subdue virus replication, recent studies demonstrate pathogenic and pro-viral roles for IFN-I signaling during acute and persistent virus infection. IFN-I signaling can promote morbidity and mortality through induction of aberrant inflammatory responses during acute viral infection. In contrast, IFN-I signaling during persistent viral infection supports immune suppression, lymphoid tissue disorganization and CD4 T cell dysfunction. Systematic characterization of the cellular populations and intricacies of IFN-I signaling that promote pathology or immune suppression during acute and persistent viral infections, respectively, should inform the development of treatments and modalities to control viral associated pathologies.",,"Teijaro, John R.",,,,
,PMC,"Atraumatic Femoral Head Necrosis in Adults: Epidemiology, Etiology, Diagnosis and Treatment",http://dx.doi.org/10.3238/arztebl.2016.0031,PMC4748149,,,"BACKGROUND: Atraumatic necrosis of the femoral head is a common cause of hip arthrosis in middle age. In Germany, it affects 5000–7000 patients per year, corresponding to an incidence of 0.01%. Though rarer than primary hip arthrosis, it is still of major clinical and socio-economic significance. Patients with this problem should be diagnosed early and given stage-appropriate treatment. METHOD: This review is based on pertinent publications that were retrieved by a selective search in the PubMed, Embase, Medline, and Cochrane Library databases using the terms “osteonecrosis,” “femoral head necrosis,” “diagnosis,” “classification,” “conservative treatment,” “surgical treatment,” “joint preservation,” “osteotomy,” and “arthroplasty,” as well as a recent guideline on atraumatic necrosis of the femoral head in adults. RESULTS: The etiology and pathogenesis of atraumatic femoral head necrosis in adults are not yet fully clear. The main risk factor is prolonged corticosteroid treatment. Nonspecific complaints and an initially normal plain x-ray of the hip can delay the diagnosis. The diagnosis is established by plain x-ray, computerized tomography, magnetic resonance tomography, and scintigraphy. Conservative treatment alone is not considered adequate. The range of surgical treatments includes joint-preserving and (for more severe necrosis) joint-resecting methods. CONCLUSION: Atraumatic femoral head necrosis in adults is a disease that progresses in stages; depending on its stage, it can either be cured or lead to hip arthrosis. A full cure is possible only in early stages. Current research focuses on the effect of new drugs on the intermediate- and long-term outcome.",,"['Arbab, Dariusch', 'König, Dietmar Pierre']",,,,
,PMC,Gene expression profiling to identify the toxicities and potentially relevant disease outcomes due to endosulfan exposure,http://dx.doi.org/10.1039/c5tx00332f,PMC6062354,,,"Endosulfan, one of the most toxic organochlorine pesticides, belongs to a group of persistent organic pollutants. Gene expression profiling offers a promising approach in health hazard identification of chemicals. The aim of this study was to use gene expression profiling to identify the toxicities and potentially relevant human diseases due to endosulfan exposure. We performed DNA microarray analysis to analyze gene expression profiles in human endothelial cells exposed to 20, 40 and 60 μM endosulfan in combination with an endothelial phenotype. Microarray results showed that endosulfan increased the number of altered genes in a dose-dependent manner, and changed the expression of 161 genes across all treatment groups. qRT-PCR closely matched the microarray data for the genes tested. Significantly enriched biological processes for overlapping down-regulated genes include the neurological system process, signal transduction, and homeostatic process in all the dose groups. These down-regulated genes were associated with cytoskeleton organization and DNA repair at low doses, and involved in cell cycle, apoptosis, p53 pathway and carcinogenesis at high doses. Those up-regulated genes were linked to the inflammatory response and transcriptional misregulation in cancer at higher doses. These findings are consistent with our established endothelial phenotypes. Endosulfan may be relevant to human diseases including liver cancer, prostate cancer and leukemia using the NextBio Human Disease Atlas. These results provide molecular evidence supporting the toxicities and carcinogenic potential of endosulfan in humans.",,"['Xu, Dan', 'Li, Shuai', 'Lin, Limei', 'Qi, Fei', 'Hang, Xiaoming', 'Sun, Yeqing']",,,,
,PMC,Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition),http://dx.doi.org/10.1080/15548627.2015.1100356,PMC4835977,,,,,"['Klionsky, Daniel J', 'Abdelmohsen, Kotb', 'Abe, Akihisa', 'Abedin, Md Joynal', 'Abeliovich, Hagai', 'Acevedo Arozena, Abraham', 'Adachi, Hiroaki', 'Adams, Christopher M', 'Adams, Peter D', 'Adeli, Khosrow', 'Adhihetty, Peter J', 'Adler, Sharon G', 'Agam, Galila', 'Agarwal, Rajesh', 'Aghi, Manish K', 'Agnello, Maria', 'Agostinis, Patrizia', 'Aguilar, Patricia V', 'Aguirre-Ghiso, Julio', 'Airoldi, Edoardo M', 'Ait-Si-Ali, Slimane', 'Akematsu, Takahiko', 'Akporiaye, Emmanuel T', 'Al-Rubeai, Mohamed', 'Albaiceta, Guillermo M', 'Albanese, Chris', 'Albani, Diego', 'Albert, Matthew L', 'Aldudo, Jesus', 'Algül, Hana', 'Alirezaei, Mehrdad', 'Alloza, Iraide', 'Almasan, Alexandru', 'Almonte-Beceril, Maylin', 'Alnemri, Emad S', 'Alonso, Covadonga', 'Altan-Bonnet, Nihal', 'Altieri, Dario C', 'Alvarez, Silvia', 'Alvarez-Erviti, Lydia', 'Alves, Sandro', 'Amadoro, Giuseppina', 'Amano, Atsuo', 'Amantini, Consuelo', 'Ambrosio, Santiago', 'Amelio, Ivano', 'Amer, Amal O', 'Amessou, Mohamed', 'Amon, Angelika', 'An, Zhenyi', 'Anania, Frank A', 'Andersen, Stig U', 'Andley, Usha P', 'Andreadi, Catherine K', 'Andrieu-Abadie, Nathalie', 'Anel, Alberto', 'Ann, David K', 'Anoopkumar-Dukie, Shailendra', 'Antonioli, Manuela', 'Aoki, Hiroshi', 'Apostolova, Nadezda', 'Aquila, Saveria', 'Aquilano, Katia', 'Araki, Koichi', 'Arama, Eli', 'Aranda, Agustin', 'Araya, Jun', 'Arcaro, Alexandre', 'Arias, Esperanza', 'Arimoto, Hirokazu', 'Ariosa, Aileen R', 'Armstrong, Jane L', 'Arnould, Thierry', 'Arsov, Ivica', 'Asanuma, Katsuhiko', 'Askanas, Valerie', 'Asselin, Eric', 'Atarashi, Ryuichiro', 'Atherton, Sally S', 'Atkin, Julie D', 'Attardi, Laura D', 'Auberger, Patrick', 'Auburger, Georg', 'Aurelian, Laure', 'Autelli, Riccardo', 'Avagliano, Laura', 'Avantaggiati, Maria Laura', 'Avrahami, Limor', 'Awale, Suresh', 'Azad, Neelam', 'Bachetti, Tiziana', 'Backer, Jonathan M', 'Bae, Dong-Hun', 'Bae, Jae-sung', 'Bae, Ok-Nam', 'Bae, Soo Han', 'Baehrecke, Eric H', 'Baek, Seung-Hoon', 'Baghdiguian, Stephen', 'Bagniewska-Zadworna, Agnieszka', 'Bai, Hua', 'Bai, Jie', 'Bai, Xue-Yuan', 'Bailly, Yannick', 'Balaji, Kithiganahalli Narayanaswamy', 'Balduini, Walter', 'Ballabio, Andrea', 'Balzan, Rena', 'Banerjee, Rajkumar', 'Bánhegyi, Gábor', 'Bao, Haijun', 'Barbeau, Benoit', 'Barrachina, Maria D', 'Barreiro, Esther', 'Bartel, Bonnie', 'Bartolomé, Alberto', 'Bassham, Diane C', 'Bassi, Maria Teresa', 'Bast, Robert C', 'Basu, Alakananda', 'Batista, Maria Teresa', 'Batoko, Henri', 'Battino, Maurizio', 'Bauckman, Kyle', 'Baumgarner, Bradley L', 'Bayer, K Ulrich', 'Beale, Rupert', 'Beaulieu, Jean-François', 'Beck, George R.', 'Becker, Christoph', 'Beckham, J David', 'Bédard, Pierre-André', 'Bednarski, Patrick J', 'Begley, Thomas J', 'Behl, Christian', 'Behrends, Christian', 'Behrens, Georg MN', 'Behrns, Kevin E', 'Bejarano, Eloy', 'Belaid, Amine', 'Belleudi, Francesca', 'Bénard, Giovanni', 'Berchem, Guy', 'Bergamaschi, Daniele', 'Bergami, Matteo', 'Berkhout, Ben', 'Berliocchi, Laura', 'Bernard, Amélie', 'Bernard, Monique', 'Bernassola, Francesca', 'Bertolotti, Anne', 'Bess, Amanda S', 'Besteiro, Sébastien', 'Bettuzzi, Saverio', 'Bhalla, Savita', 'Bhattacharyya, Shalmoli', 'Bhutia, Sujit K', 'Biagosch, Caroline', 'Bianchi, Michele Wolfe', 'Biard-Piechaczyk, Martine', 'Billes, Viktor', 'Bincoletto, Claudia', 'Bingol, Baris', 'Bird, Sara W', 'Bitoun, Marc', 'Bjedov, Ivana', 'Blackstone, Craig', 'Blanc, Lionel', 'Blanco, Guillermo A', 'Blomhoff, Heidi Kiil', 'Boada-Romero, Emilio', 'Böckler, Stefan', 'Boes, Marianne', 'Boesze-Battaglia, Kathleen', 'Boise, Lawrence H', 'Bolino, Alessandra', 'Boman, Andrea', 'Bonaldo, Paolo', 'Bordi, Matteo', 'Bosch, Jürgen', 'Botana, Luis M', 'Botti, Joelle', 'Bou, German', 'Bouché, Marina', 'Bouchecareilh, Marion', 'Boucher, Marie-Josée', 'Boulton, Michael E', 'Bouret, Sebastien G', 'Boya, Patricia', 'Boyer-Guittaut, Michaël', 'Bozhkov, Peter V', 'Brady, Nathan', 'Braga, Vania MM', 'Brancolini, Claudio', 'Braus, Gerhard H', 'Bravo-San Pedro, José M', 'Brennan, Lisa A', 'Bresnick, Emery H', 'Brest, Patrick', 'Bridges, Dave', 'Bringer, Marie-Agnès', 'Brini, Marisa', 'Brito, Glauber C', 'Brodin, Bertha', 'Brookes, Paul S', 'Brown, Eric J', 'Brown, Karen', 'Broxmeyer, Hal E', 'Bruhat, Alain', 'Brum, Patricia Chakur', 'Brumell, John H', 'Brunetti-Pierri, Nicola', 'Bryson-Richardson, Robert J', 'Buch, Shilpa', 'Buchan, Alastair M', 'Budak, Hikmet', 'Bulavin, Dmitry V', 'Bultman, Scott J', 'Bultynck, Geert', 'Bumbasirevic, Vladimir', 'Burelle, Yan', 'Burke, Robert E', 'Burmeister, Margit', 'Bütikofer, Peter', 'Caberlotto, Laura', 'Cadwell, Ken', 'Cahova, Monika', 'Cai, Dongsheng', 'Cai, Jingjing', 'Cai, Qian', 'Calatayud, Sara', 'Camougrand, Nadine', 'Campanella, Michelangelo', 'Campbell, Grant R', 'Campbell, Matthew', 'Campello, Silvia', 'Candau, Robin', 'Caniggia, Isabella', 'Cantoni, Lavinia', 'Cao, Lizhi', 'Caplan, Allan B', 'Caraglia, Michele', 'Cardinali, Claudio', 'Cardoso, Sandra Morais', 'Carew, Jennifer S', 'Carleton, Laura A', 'Carlin, Cathleen R', 'Carloni, Silvia', 'Carlsson, Sven R', 'Carmona-Gutierrez, Didac', 'Carneiro, Leticia AM', 'Carnevali, Oliana', 'Carra, Serena', 'Carrier, Alice', 'Carroll, Bernadette', 'Casas, Caty', 'Casas, Josefina', 'Cassinelli, Giuliana', 'Castets, Perrine', 'Castro-Obregon, Susana', 'Cavallini, Gabriella', 'Ceccherini, Isabella', 'Cecconi, Francesco', 'Cederbaum, Arthur I', 'Ceña, Valentín', 'Cenci, Simone', 'Cerella, Claudia', 'Cervia, Davide', 'Cetrullo, Silvia', 'Chaachouay, Hassan', 'Chae, Han-Jung', 'Chagin, Andrei S', 'Chai, Chee-Yin', 'Chakrabarti, Gopal', 'Chamilos, Georgios', 'Chan, Edmond YW', 'Chan, Matthew TV', 'Chandra, Dhyan', 'Chandra, Pallavi', 'Chang, Chih-Peng', 'Chang, Raymond Chuen-Chung', 'Chang, Ta Yuan', 'Chatham, John C', 'Chatterjee, Saurabh', 'Chauhan, Santosh', 'Che, Yongsheng', 'Cheetham, Michael E', 'Cheluvappa, Rajkumar', 'Chen, Chun-Jung', 'Chen, Gang', 'Chen, Guang-Chao', 'Chen, Guoqiang', 'Chen, Hongzhuan', 'Chen, Jeff W', 'Chen, Jian-Kang', 'Chen, Min', 'Chen, Mingzhou', 'Chen, Peiwen', 'Chen, Qi', 'Chen, Quan', 'Chen, Shang-Der', 'Chen, Si', 'Chen, Steve S-L', 'Chen, Wei', 'Chen, Wei-Jung', 'Chen, Wen Qiang', 'Chen, Wenli', 'Chen, Xiangmei', 'Chen, Yau-Hung', 'Chen, Ye-Guang', 'Chen, Yin', 'Chen, Yingyu', 'Chen, Yongshun', 'Chen, Yu-Jen', 'Chen, Yue-Qin', 'Chen, Yujie', 'Chen, Zhen', 'Chen, Zhong', 'Cheng, Alan', 'Cheng, Christopher HK', 'Cheng, Hua', 'Cheong, Heesun', 'Cherry, Sara', 'Chesney, Jason', 'Cheung, Chun Hei Antonio', 'Chevet, Eric', 'Chi, Hsiang Cheng', 'Chi, Sung-Gil', 'Chiacchiera, Fulvio', 'Chiang, Hui-Ling', 'Chiarelli, Roberto', 'Chiariello, Mario', 'Chieppa, Marcello', 'Chin, Lih-Shen', 'Chiong, Mario', 'Chiu, Gigi NC', 'Cho, Dong-Hyung', 'Cho, Ssang-Goo', 'Cho, William C', 'Cho, Yong-Yeon', 'Cho, Young-Seok', 'Choi, Augustine MK', 'Choi, Eui-Ju', 'Choi, Eun-Kyoung', 'Choi, Jayoung', 'Choi, Mary E', 'Choi, Seung-Il', 'Chou, Tsui-Fen', 'Chouaib, Salem', 'Choubey, Divaker', 'Choubey, Vinay', 'Chow, Kuan-Chih', 'Chowdhury, Kamal', 'Chu, Charleen T', 'Chuang, Tsung-Hsien', 'Chun, Taehoon', 'Chung, Hyewon', 'Chung, Taijoon', 'Chung, Yuen-Li', 'Chwae, Yong-Joon', 'Cianfanelli, Valentina', 'Ciarcia, Roberto', 'Ciechomska, Iwona A', 'Ciriolo, Maria Rosa', 'Cirone, Mara', 'Claerhout, Sofie', 'Clague, Michael J', 'Clària, Joan', 'Clarke, Peter GH', 'Clarke, Robert', 'Clementi, Emilio', 'Cleyrat, Cédric', 'Cnop, Miriam', 'Coccia, Eliana M', 'Cocco, Tiziana', 'Codogno, Patrice', 'Coers, Jörn', 'Cohen, Ezra EW', 'Colecchia, David', 'Coletto, Luisa', 'Coll, Núria S', 'Colucci-Guyon, Emma', 'Comincini, Sergio', 'Condello, Maria', 'Cook, Katherine L', 'Coombs, Graham H', 'Cooper, Cynthia D', 'Cooper, J Mark', 'Coppens, Isabelle', 'Corasaniti, Maria Tiziana', 'Corazzari, Marco', 'Corbalan, Ramon', 'Corcelle-Termeau, Elisabeth', 'Cordero, Mario D', 'Corral-Ramos, Cristina', 'Corti, Olga', 'Cossarizza, Andrea', 'Costelli, Paola', 'Costes, Safia', 'Cotman, Susan L', 'Coto-Montes, Ana', 'Cottet, Sandra', 'Couve, Eduardo', 'Covey, Lori R', 'Cowart, L Ashley', 'Cox, Jeffery S', 'Coxon, Fraser P', 'Coyne, Carolyn B', 'Cragg, Mark S', 'Craven, Rolf J', 'Crepaldi, Tiziana', 'Crespo, Jose L', 'Criollo, Alfredo', 'Crippa, Valeria', 'Cruz, Maria Teresa', 'Cuervo, Ana Maria', 'Cuezva, Jose M', 'Cui, Taixing', 'Cutillas, Pedro R', 'Czaja, Mark J', 'Czyzyk-Krzeska, Maria F', 'Dagda, Ruben K', 'Dahmen, Uta', 'Dai, Chunsun', 'Dai, Wenjie', 'Dai, Yun', 'Dalby, Kevin N', 'Dalla Valle, Luisa', 'Dalmasso, Guillaume', ""D'Amelio, Marcello"", 'Damme, Markus', 'Darfeuille-Michaud, Arlette', 'Dargemont, Catherine', 'Darley-Usmar, Victor M', 'Dasarathy, Srinivasan', 'Dasgupta, Biplab', 'Dash, Srikanta', 'Dass, Crispin R', 'Davey, Hazel Marie', 'Davids, Lester M', 'Dávila, David', 'Davis, Roger J', 'Dawson, Ted M', 'Dawson, Valina L', 'Daza, Paula', 'de Belleroche, Jackie', 'de Figueiredo, Paul', 'de Figueiredo, Regina Celia Bressan Queiroz', 'de la Fuente, José', 'De Martino, Luisa', 'De Matteis, Antonella', 'De Meyer, Guido RY', 'De Milito, Angelo', 'De Santi, Mauro', 'de Souza, Wanderley', 'De Tata, Vincenzo', 'De Zio, Daniela', 'Debnath, Jayanta', 'Dechant, Reinhard', 'Decuypere, Jean-Paul', 'Deegan, Shane', 'Dehay, Benjamin', 'Del Bello, Barbara', 'Del Re, Dominic P', 'Delage-Mourroux, Régis', 'Delbridge, Lea MD', 'Deldicque, Louise', 'Delorme-Axford, Elizabeth', 'Deng, Yizhen', 'Dengjel, Joern', 'Denizot, Melanie', 'Dent, Paul', 'Der, Channing J', 'Deretic, Vojo', 'Derrien, Benoît', 'Deutsch, Eric', 'Devarenne, Timothy P', 'Devenish, Rodney J', 'Di Bartolomeo, Sabrina', 'Di Daniele, Nicola', 'Di Domenico, Fabio', 'Di Nardo, Alessia', 'Di Paola, Simone', 'Di Pietro, Antonio', 'Di Renzo, Livia', 'DiAntonio, Aaron', 'Díaz-Araya, Guillermo', 'Díaz-Laviada, Ines', 'Diaz-Meco, Maria T', 'Diaz-Nido, Javier', 'Dickey, Chad A', 'Dickson, Robert C', 'Diederich, Marc', 'Digard, Paul', 'Dikic, Ivan', 'Dinesh-Kumar, Savithrama P', 'Ding, Chan', 'Ding, Wen-Xing', 'Ding, Zufeng', 'Dini, Luciana', 'Distler, Jörg HW', 'Diwan, Abhinav', 'Djavaheri-Mergny, Mojgan', 'Dmytruk, Kostyantyn', 'Dobson, Renwick CJ', 'Doetsch, Volker', 'Dokladny, Karol', 'Dokudovskaya, Svetlana', 'Donadelli, Massimo', 'Dong, X Charlie', 'Dong, Xiaonan', 'Dong, Zheng', 'Donohue, Terrence M', 'Doran, Kelly S', ""D'Orazi, Gabriella"", 'Dorn, Gerald W', 'Dosenko, Victor', 'Dridi, Sami', 'Drucker, Liat', 'Du, Jie', 'Du, Li-Lin', 'Du, Lihuan', 'du Toit, André', 'Dua, Priyamvada', 'Duan, Lei', 'Duann, Pu', 'Dubey, Vikash Kumar', 'Duchen, Michael R', 'Duchosal, Michel A', 'Duez, Helene', 'Dugail, Isabelle', 'Dumit, Verónica I', 'Duncan, Mara C', 'Dunlop, Elaine A', 'Dunn, William A', 'Dupont, Nicolas', 'Dupuis, Luc', 'Durán, Raúl V', 'Durcan, Thomas M', 'Duvezin-Caubet, Stéphane', 'Duvvuri, Umamaheswar', 'Eapen, Vinay', 'Ebrahimi-Fakhari, Darius', 'Echard, Arnaud', 'Eckhart, Leopold', 'Edelstein, Charles L', 'Edinger, Aimee L', 'Eichinger, Ludwig', 'Eisenberg, Tobias', 'Eisenberg-Lerner, Avital', 'Eissa, N Tony', 'El-Deiry, Wafik S', 'El-Khoury, Victoria', 'Elazar, Zvulun', 'Eldar-Finkelman, Hagit', 'Elliott, Chris JH', 'Emanuele, Enzo', 'Emmenegger, Urban', 'Engedal, Nikolai', 'Engelbrecht, Anna-Mart', 'Engelender, Simone', 'Enserink, Jorrit M', 'Erdmann, Ralf', 'Erenpreisa, Jekaterina', 'Eri, Rajaraman', 'Eriksen, Jason L', 'Erman, Andreja', 'Escalante, Ricardo', 'Eskelinen, Eeva-Liisa', 'Espert, Lucile', 'Esteban-Martínez, Lorena', 'Evans, Thomas J', 'Fabri, Mario', 'Fabrias, Gemma', 'Fabrizi, Cinzia', 'Facchiano, Antonio', 'Færgeman, Nils J', 'Faggioni, Alberto', 'Fairlie, W Douglas', 'Fan, Chunhai', 'Fan, Daping', 'Fan, Jie', 'Fang, Shengyun', 'Fanto, Manolis', 'Fanzani, Alessandro', 'Farkas, Thomas', 'Faure, Mathias', 'Favier, Francois B', 'Fearnhead, Howard', 'Federici, Massimo', 'Fei, Erkang', 'Felizardo, Tania C', 'Feng, Hua', 'Feng, Yibin', 'Feng, Yuchen', 'Ferguson, Thomas A', 'Fernández, Álvaro F', 'Fernandez-Barrena, Maite G', 'Fernandez-Checa, Jose C', 'Fernández-López, Arsenio', 'Fernandez-Zapico, Martin E', 'Feron, Olivier', 'Ferraro, Elisabetta', 'Ferreira-Halder, Carmen Veríssima', 'Fesus, Laszlo', 'Feuer, Ralph', 'Fiesel, Fabienne C', 'Filippi-Chiela, Eduardo C', 'Filomeni, Giuseppe', 'Fimia, Gian Maria', 'Fingert, John H', 'Finkbeiner, Steven', 'Finkel, Toren', 'Fiorito, Filomena', 'Fisher, Paul B', 'Flajolet, Marc', 'Flamigni, Flavio', 'Florey, Oliver', 'Florio, Salvatore', 'Floto, R Andres', 'Folini, Marco', 'Follo, Carlo', 'Fon, Edward A', 'Fornai, Francesco', 'Fortunato, Franco', 'Fraldi, Alessandro', 'Franco, Rodrigo', 'Francois, Arnaud', 'François, Aurélie', 'Frankel, Lisa B', 'Fraser, Iain DC', 'Frey, Norbert', 'Freyssenet, Damien G', 'Frezza, Christian', 'Friedman, Scott L', 'Frigo, Daniel E', 'Fu, Dongxu', 'Fuentes, José M', 'Fueyo, Juan', 'Fujitani, Yoshio', 'Fujiwara, Yuuki', 'Fujiya, Mikihiro', 'Fukuda, Mitsunori', 'Fulda, Simone', 'Fusco, Carmela', 'Gabryel, Bozena', 'Gaestel, Matthias', 'Gailly, Philippe', 'Gajewska, Malgorzata', 'Galadari, Sehamuddin', 'Galili, Gad', 'Galindo, Inmaculada', 'Galindo, Maria F', 'Galliciotti, Giovanna', 'Galluzzi, Lorenzo', 'Galluzzi, Luca', 'Galy, Vincent', 'Gammoh, Noor', 'Gandy, Sam', 'Ganesan, Anand K', 'Ganesan, Swamynathan', 'Ganley, Ian G', 'Gannagé, Monique', 'Gao, Fen-Biao', 'Gao, Feng', 'Gao, Jian-Xin', 'García Nannig, Lorena', 'García Véscovi, Eleonora', 'Garcia-Macía, Marina', 'Garcia-Ruiz, Carmen', 'Garg, Abhishek D', 'Garg, Pramod Kumar', 'Gargini, Ricardo', 'Gassen, Nils Christian', 'Gatica, Damián', 'Gatti, Evelina', 'Gavard, Julie', 'Gavathiotis, Evripidis', 'Ge, Liang', 'Ge, Pengfei', 'Ge, Shengfang', 'Gean, Po-Wu', 'Gelmetti, Vania', 'Genazzani, Armando A', 'Geng, Jiefei', 'Genschik, Pascal', 'Gerner, Lisa', 'Gestwicki, Jason E', 'Gewirtz, David A', 'Ghavami, Saeid', 'Ghigo, Eric', 'Ghosh, Debabrata', 'Giammarioli, Anna Maria', 'Giampieri, Francesca', 'Giampietri, Claudia', 'Giatromanolaki, Alexandra', 'Gibbings, Derrick J', 'Gibellini, Lara', 'Gibson, Spencer B', 'Ginet, Vanessa', 'Giordano, Antonio', 'Giorgini, Flaviano', 'Giovannetti, Elisa', 'Girardin, Stephen E', 'Gispert, Suzana', 'Giuliano, Sandy', 'Gladson, Candece L', 'Glavic, Alvaro', 'Gleave, Martin', 'Godefroy, Nelly', 'Gogal, Robert M', 'Gokulan, Kuppan', 'Goldman, Gustavo H', 'Goletti, Delia', 'Goligorsky, Michael S', 'Gomes, Aldrin V', 'Gomes, Ligia C', 'Gomez, Hernando', 'Gomez-Manzano, Candelaria', 'Gómez-Sánchez, Rubén', 'Gonçalves, Dawit AP', 'Goncu, Ebru', 'Gong, Qingqiu', 'Gongora, Céline', 'Gonzalez, Carlos B', 'Gonzalez-Alegre, Pedro', 'Gonzalez-Cabo, Pilar', 'González-Polo, Rosa Ana', 'Goping, Ing Swie', 'Gorbea, Carlos', 'Gorbunov, Nikolai V', 'Goring, Daphne R', 'Gorman, Adrienne M', 'Gorski, Sharon M', 'Goruppi, Sandro', 'Goto-Yamada, Shino', 'Gotor, Cecilia', 'Gottlieb, Roberta A', 'Gozes, Illana', 'Gozuacik, Devrim', 'Graba, Yacine', 'Graef, Martin', 'Granato, Giovanna E', 'Grant, Gary Dean', 'Grant, Steven', 'Gravina, Giovanni Luca', 'Green, Douglas R', 'Greenhough, Alexander', 'Greenwood, Michael T', 'Grimaldi, Benedetto', 'Gros, Frédéric', 'Grose, Charles', 'Groulx, Jean-Francois', 'Gruber, Florian', 'Grumati, Paolo', 'Grune, Tilman', 'Guan, Jun-Lin', 'Guan, Kun-Liang', 'Guerra, Barbara', 'Guillen, Carlos', 'Gulshan, Kailash', 'Gunst, Jan', 'Guo, Chuanyong', 'Guo, Lei', 'Guo, Ming', 'Guo, Wenjie', 'Guo, Xu-Guang', 'Gust, Andrea A', 'Gustafsson, Åsa B', 'Gutierrez, Elaine', 'Gutierrez, Maximiliano G', 'Gwak, Ho-Shin', 'Haas, Albert', 'Haber, James E', 'Hadano, Shinji', 'Hagedorn, Monica', 'Hahn, David R', 'Halayko, Andrew J', 'Hamacher-Brady, Anne', 'Hamada, Kozo', 'Hamai, Ahmed', 'Hamann, Andrea', 'Hamasaki, Maho', 'Hamer, Isabelle', 'Hamid, Qutayba', 'Hammond, Ester M', 'Han, Feng', 'Han, Weidong', 'Handa, James T', 'Hanover, John A', 'Hansen, Malene', 'Harada, Masaru', 'Harhaji-Trajkovic, Ljubica', 'Harper, J Wade', 'Harrath, Abdel Halim', 'Harris, Adrian L', 'Harris, James', 'Hasler, Udo', 'Hasselblatt, Peter', 'Hasui, Kazuhisa', 'Hawley, Robert G', 'Hawley, Teresa S', 'He, Congcong', 'He, Cynthia Y', 'He, Fengtian', 'He, Gu', 'He, Rong-Rong', 'He, Xian-Hui', 'He, You-Wen', 'He, Yu-Ying', 'Heath, Joan K', 'Hébert, Marie-Josée', 'Heinzen, Robert A', 'Helgason, Gudmundur Vignir', 'Hensel, Michael', 'Henske, Elizabeth P', 'Her, Chengtao', 'Herman, Paul K', 'Hernández, Agustín', 'Hernandez, Carlos', 'Hernández-Tiedra, Sonia', 'Hetz, Claudio', 'Hiesinger, P Robin', 'Higaki, Katsumi', 'Hilfiker, Sabine', 'Hill, Bradford G', 'Hill, Joseph A', 'Hill, William D', 'Hino, Keisuke', 'Hofius, Daniel', 'Hofman, Paul', 'Höglinger, Günter U', 'Höhfeld, Jörg', 'Holz, Marina K', 'Hong, Yonggeun', 'Hood, David A', 'Hoozemans, Jeroen JM', 'Hoppe, Thorsten', 'Hsu, Chin', 'Hsu, Chin-Yuan', 'Hsu, Li-Chung', 'Hu, Dong', 'Hu, Guochang', 'Hu, Hong-Ming', 'Hu, Hongbo', 'Hu, Ming Chang', 'Hu, Yu-Chen', 'Hu, Zhuo-Wei', 'Hua, Fang', 'Hua, Ya', 'Huang, Canhua', 'Huang, Huey-Lan', 'Huang, Kuo-How', 'Huang, Kuo-Yang', 'Huang, Shile', 'Huang, Shiqian', 'Huang, Wei-Pang', 'Huang, Yi-Ran', 'Huang, Yong', 'Huang, Yunfei', 'Huber, Tobias B', 'Huebbe, Patricia', 'Huh, Won-Ki', 'Hulmi, Juha J', 'Hur, Gang Min', 'Hurley, James H', 'Husak, Zvenyslava', 'Hussain, Sabah NA', 'Hussain, Salik', 'Hwang, Jung Jin', 'Hwang, Seungmin', 'Hwang, Thomas IS', 'Ichihara, Atsuhiro', 'Imai, Yuzuru', 'Imbriano, Carol', 'Inomata, Megumi', 'Into, Takeshi', 'Iovane, Valentina', 'Iovanna, Juan L', 'Iozzo, Renato V', 'Ip, Nancy Y', 'Irazoqui, Javier E', 'Iribarren, Pablo', 'Isaka, Yoshitaka', 'Isakovic, Aleksandra J', 'Ischiropoulos, Harry', 'Isenberg, Jeffrey S', 'Ishaq, Mohammad', 'Ishida, Hiroyuki', 'Ishii, Isao', 'Ishmael, Jane E', 'Isidoro, Ciro', 'Isobe, Ken-ichi', 'Isono, Erika', 'Issazadeh-Navikas, Shohreh', 'Itahana, Koji', 'Itakura, Eisuke', 'Ivanov, Andrei I', 'Iyer, Anand Krishnan V', 'Izquierdo, José M', 'Izumi, Yotaro', 'Izzo, Valentina', 'Jäättelä, Marja', 'Jaber, Nadia', 'Jackson, Daniel John', 'Jackson, William T', 'Jacob, Tony George', 'Jacques, Thomas S', 'Jagannath, Chinnaswamy', 'Jain, Ashish', 'Jana, Nihar Ranjan', 'Jang, Byoung Kuk', 'Jani, Alkesh', 'Janji, Bassam', 'Jannig, Paulo Roberto', 'Jansson, Patric J', 'Jean, Steve', 'Jendrach, Marina', 'Jeon, Ju-Hong', 'Jessen, Niels', 'Jeung, Eui-Bae', 'Jia, Kailiang', 'Jia, Lijun', 'Jiang, Hong', 'Jiang, Hongchi', 'Jiang, Liwen', 'Jiang, Teng', 'Jiang, Xiaoyan', 'Jiang, Xuejun', 'Jiang, Xuejun', 'Jiang, Ying', 'Jiang, Yongjun', 'Jiménez, Alberto', 'Jin, Cheng', 'Jin, Hongchuan', 'Jin, Lei', 'Jin, Meiyan', 'Jin, Shengkan', 'Jinwal, Umesh Kumar', 'Jo, Eun-Kyeong', 'Johansen, Terje', 'Johnson, Daniel E', 'Johnson, Gail VW', 'Johnson, James D', 'Jonasch, Eric', 'Jones, Chris', 'Joosten, Leo AB', 'Jordan, Joaquin', 'Joseph, Anna-Maria', 'Joseph, Bertrand', 'Joubert, Annie M', 'Ju, Dianwen', 'Ju, Jingfang', 'Juan, Hsueh-Fen', 'Juenemann, Katrin', 'Juhász, Gábor', 'Jung, Hye Seung', 'Jung, Jae U', 'Jung, Yong-Keun', 'Jungbluth, Heinz', 'Justice, Matthew J', 'Jutten, Barry', 'Kaakoush, Nadeem O', 'Kaarniranta, Kai', 'Kaasik, Allen', 'Kabuta, Tomohiro', 'Kaeffer, Bertrand', 'Kågedal, Katarina', 'Kahana, Alon', 'Kajimura, Shingo', 'Kakhlon, Or', 'Kalia, Manjula', 'Kalvakolanu, Dhan V', 'Kamada, Yoshiaki', 'Kambas, Konstantinos', 'Kaminskyy, Vitaliy O', 'Kampinga, Harm H', 'Kandouz, Mustapha', 'Kang, Chanhee', 'Kang, Rui', 'Kang, Tae-Cheon', 'Kanki, Tomotake', 'Kanneganti, Thirumala-Devi', 'Kanno, Haruo', 'Kanthasamy, Anumantha G', 'Kantorow, Marc', 'Kaparakis-Liaskos, Maria', 'Kapuy, Orsolya', 'Karantza, Vassiliki', 'Karim, Md Razaul', 'Karmakar, Parimal', 'Kaser, Arthur', 'Kaushik, Susmita', 'Kawula, Thomas', 'Kaynar, A Murat', 'Ke, Po-Yuan', 'Ke, Zun-Ji', 'Kehrl, John H', 'Keller, Kate E', 'Kemper, Jongsook Kim', 'Kenworthy, Anne K', 'Kepp, Oliver', 'Kern, Andreas', 'Kesari, Santosh', 'Kessel, David', 'Ketteler, Robin', 'Kettelhut, Isis do Carmo', 'Khambu, Bilon', 'Khan, Muzamil Majid', 'Khandelwal, Vinoth KM', 'Khare, Sangeeta', 'Kiang, Juliann G', 'Kiger, Amy A', 'Kihara, Akio', 'Kim, Arianna L', 'Kim, Cheol Hyeon', 'Kim, Deok Ryong', 'Kim, Do-Hyung', 'Kim, Eung Kweon', 'Kim, Hye Young', 'Kim, Hyung-Ryong', 'Kim, Jae-Sung', 'Kim, Jeong Hun', 'Kim, Jin Cheon', 'Kim, Jin Hyoung', 'Kim, Kwang Woon', 'Kim, Michael D', 'Kim, Moon-Moo', 'Kim, Peter K', 'Kim, Seong Who', 'Kim, Soo-Youl', 'Kim, Yong-Sun', 'Kim, Yonghyun', 'Kimchi, Adi', 'Kimmelman, Alec C', 'Kimura, Tomonori', 'King, Jason S', 'Kirkegaard, Karla', 'Kirkin, Vladimir', 'Kirshenbaum, Lorrie A', 'Kishi, Shuji', 'Kitajima, Yasuo', 'Kitamoto, Katsuhiko', 'Kitaoka, Yasushi', 'Kitazato, Kaio', 'Kley, Rudolf A', 'Klimecki, Walter T', 'Klinkenberg, Michael', 'Klucken, Jochen', 'Knævelsrud, Helene', 'Knecht, Erwin', 'Knuppertz, Laura', 'Ko, Jiunn-Liang', 'Kobayashi, Satoru', 'Koch, Jan C', 'Koechlin-Ramonatxo, Christelle', 'Koenig, Ulrich', 'Koh, Young Ho', 'Köhler, Katja', 'Kohlwein, Sepp D', 'Koike, Masato', 'Komatsu, Masaaki', 'Kominami, Eiki', 'Kong, Dexin', 'Kong, Hee Jeong', 'Konstantakou, Eumorphia G', 'Kopp, Benjamin T', 'Korcsmaros, Tamas', 'Korhonen, Laura', 'Korolchuk, Viktor I', 'Koshkina, Nadya V', 'Kou, Yanjun', 'Koukourakis, Michael I', 'Koumenis, Constantinos', 'Kovács, Attila L', 'Kovács, Tibor', 'Kovacs, Werner J', 'Koya, Daisuke', 'Kraft, Claudine', 'Krainc, Dimitri', 'Kramer, Helmut', 'Kravic-Stevovic, Tamara', 'Krek, Wilhelm', 'Kretz-Remy, Carole', 'Krick, Roswitha', 'Krishnamurthy, Malathi', 'Kriston-Vizi, Janos', 'Kroemer, Guido', 'Kruer, Michael C', 'Kruger, Rejko', 'Ktistakis, Nicholas T', 'Kuchitsu, Kazuyuki', 'Kuhn, Christian', 'Kumar, Addanki Pratap', 'Kumar, Anuj', 'Kumar, Ashok', 'Kumar, Deepak', 'Kumar, Dhiraj', 'Kumar, Rakesh', 'Kumar, Sharad', 'Kundu, Mondira', 'Kung, Hsing-Jien', 'Kuno, Atsushi', 'Kuo, Sheng-Han', 'Kuret, Jeff', 'Kurz, Tino', 'Kwok, Terry', 'Kwon, Taeg Kyu', 'Kwon, Yong Tae', 'Kyrmizi, Irene', 'La Spada, Albert R', 'Lafont, Frank', 'Lahm, Tim', 'Lakkaraju, Aparna', 'Lam, Truong', 'Lamark, Trond', 'Lancel, Steve', 'Landowski, Terry H', 'Lane, Darius JR', 'Lane, Jon D', 'Lanzi, Cinzia', 'Lapaquette, Pierre', 'Lapierre, Louis R', 'Laporte, Jocelyn', 'Laukkarinen, Johanna', 'Laurie, Gordon W', 'Lavandero, Sergio', 'Lavie, Lena', 'LaVoie, Matthew J', 'Law, Betty Yuen Kwan', 'Law, Helen Ka-wai', 'Law, Kelsey B', 'Layfield, Robert', 'Lazo, Pedro A', 'Le Cam, Laurent', 'Le Roch, Karine G', 'Le Stunff, Hervé', 'Leardkamolkarn, Vijittra', 'Lecuit, Marc', 'Lee, Byung-Hoon', 'Lee, Che-Hsin', 'Lee, Erinna F', 'Lee, Gyun Min', 'Lee, He-Jin', 'Lee, Hsinyu', 'Lee, Jae Keun', 'Lee, Jongdae', 'Lee, Ju-hyun', 'Lee, Jun Hee', 'Lee, Michael', 'Lee, Myung-Shik', 'Lee, Patty J', 'Lee, Sam W', 'Lee, Seung-Jae', 'Lee, Shiow-Ju', 'Lee, Stella Y', 'Lee, Sug Hyung', 'Lee, Sung Sik', 'Lee, Sung-Joon', 'Lee, Sunhee', 'Lee, Ying-Ray', 'Lee, Yong J', 'Lee, Young H', 'Leeuwenburgh, Christiaan', 'Lefort, Sylvain', 'Legouis, Renaud', 'Lei, Jinzhi', 'Lei, Qun-Ying', 'Leib, David A', 'Leibowitz, Gil', 'Lekli, Istvan', 'Lemaire, Stéphane D', 'Lemasters, John J', 'Lemberg, Marius K', 'Lemoine, Antoinette', 'Leng, Shuilong', 'Lenz, Guido', 'Lenzi, Paola', 'Lerman, Lilach O', 'Lettieri Barbato, Daniele', 'Leu, Julia I-Ju', 'Leung, Hing Y', 'Levine, Beth', 'Lewis, Patrick A', ""Lezoualc'h, Frank"", 'Li, Chi', 'Li, Faqiang', 'Li, Feng-Jun', 'Li, Jun', 'Li, Ke', 'Li, Lian', 'Li, Min', 'Li, Min', 'Li, Qiang', 'Li, Rui', 'Li, Sheng', 'Li, Wei', 'Li, Wei', 'Li, Xiaotao', 'Li, Yumin', 'Lian, Jiqin', 'Liang, Chengyu', 'Liang, Qiangrong', 'Liao, Yulin', 'Liberal, Joana', 'Liberski, Pawel P', 'Lie, Pearl', 'Lieberman, Andrew P', 'Lim, Hyunjung Jade', 'Lim, Kah-Leong', 'Lim, Kyu', 'Lima, Raquel T', 'Lin, Chang-Shen', 'Lin, Chiou-Feng', 'Lin, Fang', 'Lin, Fangming', 'Lin, Fu-Cheng', 'Lin, Kui', 'Lin, Kwang-Huei', 'Lin, Pei-Hui', 'Lin, Tianwei', 'Lin, Wan-Wan', 'Lin, Yee-Shin', 'Lin, Yong', 'Linden, Rafael', 'Lindholm, Dan', 'Lindqvist, Lisa M', 'Lingor, Paul', 'Linkermann, Andreas', 'Liotta, Lance A', 'Lipinski, Marta M', 'Lira, Vitor A', 'Lisanti, Michael P', 'Liton, Paloma B', 'Liu, Bo', 'Liu, Chong', 'Liu, Chun-Feng', 'Liu, Fei', 'Liu, Hung-Jen', 'Liu, Jianxun', 'Liu, Jing-Jing', 'Liu, Jing-Lan', 'Liu, Ke', 'Liu, Leyuan', 'Liu, Liang', 'Liu, Quentin', 'Liu, Rong-Yu', 'Liu, Shiming', 'Liu, Shuwen', 'Liu, Wei', 'Liu, Xian-De', 'Liu, Xiangguo', 'Liu, Xiao-Hong', 'Liu, Xinfeng', 'Liu, Xu', 'Liu, Xueqin', 'Liu, Yang', 'Liu, Yule', 'Liu, Zexian', 'Liu, Zhe', 'Liuzzi, Juan P', 'Lizard, Gérard', 'Ljujic, Mila', 'Lodhi, Irfan J', 'Logue, Susan E', 'Lokeshwar, Bal L', 'Long, Yun Chau', 'Lonial, Sagar', 'Loos, Benjamin', 'López-Otín, Carlos', 'López-Vicario, Cristina', 'Lorente, Mar', 'Lorenzi, Philip L', 'Lõrincz, Péter', 'Los, Marek', 'Lotze, Michael T', 'Lovat, Penny E', 'Lu, Binfeng', 'Lu, Bo', 'Lu, Jiahong', 'Lu, Qing', 'Lu, She-Min', 'Lu, Shuyan', 'Lu, Yingying', 'Luciano, Frédéric', 'Luckhart, Shirley', 'Lucocq, John Milton', 'Ludovico, Paula', 'Lugea, Aurelia', 'Lukacs, Nicholas W', 'Lum, Julian J', 'Lund, Anders H', 'Luo, Honglin', 'Luo, Jia', 'Luo, Shouqing', 'Luparello, Claudio', 'Lyons, Timothy', 'Ma, Jianjie', 'Ma, Yi', 'Ma, Yong', 'Ma, Zhenyi', 'Machado, Juliano', 'Machado-Santelli, Glaucia M', 'Macian, Fernando', 'MacIntosh, Gustavo C', 'MacKeigan, Jeffrey P', 'Macleod, Kay F', 'MacMicking, John D', 'MacMillan-Crow, Lee Ann', 'Madeo, Frank', 'Madesh, Muniswamy', 'Madrigal-Matute, Julio', 'Maeda, Akiko', 'Maeda, Tatsuya', 'Maegawa, Gustavo', 'Maellaro, Emilia', 'Maes, Hannelore', 'Magariños, Marta', 'Maiese, Kenneth', 'Maiti, Tapas K', 'Maiuri, Luigi', 'Maiuri, Maria Chiara', 'Maki, Carl G', 'Malli, Roland', 'Malorni, Walter', 'Maloyan, Alina', 'Mami-Chouaib, Fathia', 'Man, Na', 'Mancias, Joseph D', 'Mandelkow, Eva-Maria', 'Mandell, Michael A', 'Manfredi, Angelo A', 'Manié, Serge N', 'Manzoni, Claudia', 'Mao, Kai', 'Mao, Zixu', 'Mao, Zong-Wan', 'Marambaud, Philippe', 'Marconi, Anna Maria', 'Marelja, Zvonimir', 'Marfe, Gabriella', 'Margeta, Marta', 'Margittai, Eva', 'Mari, Muriel', 'Mariani, Francesca V', 'Marin, Concepcio', 'Marinelli, Sara', 'Mariño, Guillermo', 'Markovic, Ivanka', 'Marquez, Rebecca', 'Martelli, Alberto M', 'Martens, Sascha', 'Martin, Katie R', 'Martin, Seamus J', 'Martin, Shaun', 'Martin-Acebes, Miguel A', 'Martín-Sanz, Paloma', 'Martinand-Mari, Camille', 'Martinet, Wim', 'Martinez, Jennifer', 'Martinez-Lopez, Nuria', 'Martinez-Outschoorn, Ubaldo', 'Martínez-Velázquez, Moisés', 'Martinez-Vicente, Marta', 'Martins, Waleska Kerllen', 'Mashima, Hirosato', 'Mastrianni, James A', 'Matarese, Giuseppe', 'Matarrese, Paola', 'Mateo, Roberto', 'Matoba, Satoaki', 'Matsumoto, Naomichi', 'Matsushita, Takehiko', 'Matsuura, Akira', 'Matsuzawa, Takeshi', 'Mattson, Mark P', 'Matus, Soledad', 'Maugeri, Norma', 'Mauvezin, Caroline', 'Mayer, Andreas', 'Maysinger, Dusica', 'Mazzolini, Guillermo D', 'McBrayer, Mary Kate', 'McCall, Kimberly', 'McCormick, Craig', 'McInerney, Gerald M', 'McIver, Skye C', 'McKenna, Sharon', 'McMahon, John J', 'McNeish, Iain A', 'Mechta-Grigoriou, Fatima', 'Medema, Jan Paul', 'Medina, Diego L', 'Megyeri, Klara', 'Mehrpour, Maryam', 'Mehta, Jawahar L', 'Mei, Yide', 'Meier, Ute-Christiane', 'Meijer, Alfred J', 'Meléndez, Alicia', 'Melino, Gerry', 'Melino, Sonia', 'de Melo, Edesio Jose Tenorio', 'Mena, Maria A', 'Meneghini, Marc D', 'Menendez, Javier A', 'Menezes, Regina', 'Meng, Liesu', 'Meng, Ling-hua', 'Meng, Songshu', 'Menghini, Rossella', 'Menko, A Sue', 'Menna-Barreto, Rubem FS', 'Menon, Manoj B', 'Meraz-Ríos, Marco A', 'Merla, Giuseppe', 'Merlini, Luciano', 'Merlot, Angelica M', 'Meryk, Andreas', 'Meschini, Stefania', 'Meyer, Joel N', 'Mi, Man-tian', 'Miao, Chao-Yu', 'Micale, Lucia', 'Michaeli, Simon', 'Michiels, Carine', 'Migliaccio, Anna Rita', 'Mihailidou, Anastasia Susie', 'Mijaljica, Dalibor', 'Mikoshiba, Katsuhiko', 'Milan, Enrico', 'Miller-Fleming, Leonor', 'Mills, Gordon B', 'Mills, Ian G', 'Minakaki, Georgia', 'Minassian, Berge A', 'Ming, Xiu-Fen', 'Minibayeva, Farida', 'Minina, Elena A', 'Mintern, Justine D', 'Minucci, Saverio', 'Miranda-Vizuete, Antonio', 'Mitchell, Claire H', 'Miyamoto, Shigeki', 'Miyazawa, Keisuke', 'Mizushima, Noboru', 'Mnich, Katarzyna', 'Mograbi, Baharia', 'Mohseni, Simin', 'Moita, Luis Ferreira', 'Molinari, Marco', 'Molinari, Maurizio', 'Møller, Andreas Buch', 'Mollereau, Bertrand', 'Mollinedo, Faustino', 'Mongillo, Marco', 'Monick, Martha M', 'Montagnaro, Serena', 'Montell, Craig', 'Moore, Darren J', 'Moore, Michael N', 'Mora-Rodriguez, Rodrigo', 'Moreira, Paula I', 'Morel, Etienne', 'Morelli, Maria Beatrice', 'Moreno, Sandra', 'Morgan, Michael J', 'Moris, Arnaud', 'Moriyasu, Yuji', 'Morrison, Janna L', 'Morrison, Lynda A', 'Morselli, Eugenia', 'Moscat, Jorge', 'Moseley, Pope L', 'Mostowy, Serge', 'Motori, Elisa', 'Mottet, Denis', 'Mottram, Jeremy C', 'Moussa, Charbel E-H', 'Mpakou, Vassiliki E', 'Mukhtar, Hasan', 'Mulcahy Levy, Jean M', 'Muller, Sylviane', 'Muñoz-Moreno, Raquel', 'Muñoz-Pinedo, Cristina', 'Münz, Christian', 'Murphy, Maureen E', 'Murray, James T', 'Murthy, Aditya', 'Mysorekar, Indira U', 'Nabi, Ivan R', 'Nabissi, Massimo', 'Nader, Gustavo A', 'Nagahara, Yukitoshi', 'Nagai, Yoshitaka', 'Nagata, Kazuhiro', 'Nagelkerke, Anika', 'Nagy, Péter', 'Naidu, Samisubbu R', 'Nair, Sreejayan', 'Nakano, Hiroyasu', 'Nakatogawa, Hitoshi', 'Nanjundan, Meera', 'Napolitano, Gennaro', 'Naqvi, Naweed I', 'Nardacci, Roberta', 'Narendra, Derek P', 'Narita, Masashi', 'Nascimbeni, Anna Chiara', 'Natarajan, Ramesh', 'Navegantes, Luiz C', 'Nawrocki, Steffan T', 'Nazarko, Taras Y', 'Nazarko, Volodymyr Y', 'Neill, Thomas', 'Neri, Luca M', 'Netea, Mihai G', 'Netea-Maier, Romana T', 'Neves, Bruno M', 'Ney, Paul A', 'Nezis, Ioannis P', 'Nguyen, Hang TT', 'Nguyen, Huu Phuc', 'Nicot, Anne-Sophie', 'Nilsen, Hilde', 'Nilsson, Per', 'Nishimura, Mikio', 'Nishino, Ichizo', 'Niso-Santano, Mireia', 'Niu, Hua', 'Nixon, Ralph A', 'Njar, Vincent CO', 'Noda, Takeshi', 'Noegel, Angelika A', 'Nolte, Elsie Magdalena', 'Norberg, Erik', 'Norga, Koenraad K', 'Noureini, Sakineh Kazemi', 'Notomi, Shoji', 'Notterpek, Lucia', 'Nowikovsky, Karin', 'Nukina, Nobuyuki', 'Nürnberger, Thorsten', ""O'Donnell, Valerie B"", ""O'Donovan, Tracey"", ""O'Dwyer, Peter J"", 'Oehme, Ina', 'Oeste, Clara L', 'Ogawa, Michinaga', 'Ogretmen, Besim', 'Ogura, Yuji', 'Oh, Young J', 'Ohmuraya, Masaki', 'Ohshima, Takayuki', 'Ojha, Rani', 'Okamoto, Koji', 'Okazaki, Toshiro', 'Oliver, F Javier', 'Ollinger, Karin', 'Olsson, Stefan', 'Orban, Daniel P', 'Ordonez, Paulina', 'Orhon, Idil', 'Orosz, Laszlo', ""O'Rourke, Eyleen J"", 'Orozco, Helena', 'Ortega, Angel L', 'Ortona, Elena', 'Osellame, Laura D', 'Oshima, Junko', 'Oshima, Shigeru', 'Osiewacz, Heinz D', 'Otomo, Takanobu', 'Otsu, Kinya', 'Ou, Jing-hsiung James', 'Outeiro, Tiago F', 'Ouyang, Dong-yun', 'Ouyang, Hongjiao', 'Overholtzer, Michael', 'Ozbun, Michelle A', 'Ozdinler, P Hande', 'Ozpolat, Bulent', 'Pacelli, Consiglia', 'Paganetti, Paolo', 'Page, Guylène', 'Pages, Gilles', 'Pagnini, Ugo', 'Pajak, Beata', 'Pak, Stephen C', 'Pakos-Zebrucka, Karolina', 'Pakpour, Nazzy', 'Palková, Zdena', 'Palladino, Francesca', 'Pallauf, Kathrin', 'Pallet, Nicolas', 'Palmieri, Marta', 'Paludan, Søren R', 'Palumbo, Camilla', 'Palumbo, Silvia', 'Pampliega, Olatz', 'Pan, Hongming', 'Pan, Wei', 'Panaretakis, Theocharis', 'Pandey, Aseem', 'Pantazopoulou, Areti', 'Papackova, Zuzana', 'Papademetrio, Daniela L', 'Papassideri, Issidora', 'Papini, Alessio', 'Parajuli, Nirmala', 'Pardo, Julian', 'Parekh, Vrajesh V', 'Parenti, Giancarlo', 'Park, Jong-In', 'Park, Junsoo', 'Park, Ohkmae K', 'Parker, Roy', 'Parlato, Rosanna', 'Parys, Jan B', 'Parzych, Katherine R', 'Pasquet, Jean-Max', 'Pasquier, Benoit', 'Pasumarthi, Kishore BS', 'Patschan, Daniel', 'Patterson, Cam', 'Pattingre, Sophie', 'Pattison, Scott', 'Pause, Arnim', 'Pavenstädt, Hermann', 'Pavone, Flaminia', 'Pedrozo, Zully', 'Peña, Fernando J', 'Peñalva, Miguel A', 'Pende, Mario', 'Peng, Jianxin', 'Penna, Fabio', 'Penninger, Josef M', 'Pensalfini, Anna', 'Pepe, Salvatore', 'Pereira, Gustavo JS', 'Pereira, Paulo C', 'Pérez-de la Cruz, Verónica', 'Pérez-Pérez, María Esther', 'Pérez-Rodríguez, Diego', 'Pérez-Sala, Dolores', 'Perier, Celine', 'Perl, Andras', 'Perlmutter, David H', 'Perrotta, Ida', 'Pervaiz, Shazib', 'Pesonen, Maija', 'Pessin, Jeffrey E', 'Peters, Godefridus J', 'Petersen, Morten', 'Petrache, Irina', 'Petrof, Basil J', 'Petrovski, Goran', 'Phang, James M', 'Piacentini, Mauro', 'Pierdominici, Marina', 'Pierre, Philippe', 'Pierrefite-Carle, Valérie', 'Pietrocola, Federico', 'Pimentel-Muiños, Felipe X', 'Pinar, Mario', 'Pineda, Benjamin', 'Pinkas-Kramarski, Ronit', 'Pinti, Marcello', 'Pinton, Paolo', 'Piperdi, Bilal', 'Piret, James M', 'Platanias, Leonidas C', 'Platta, Harald W', 'Plowey, Edward D', 'Pöggeler, Stefanie', 'Poirot, Marc', 'Polčic, Peter', 'Poletti, Angelo', 'Poon, Audrey H', 'Popelka, Hana', 'Popova, Blagovesta', 'Poprawa, Izabela', 'Poulose, Shibu M', 'Poulton, Joanna', 'Powers, Scott K', 'Powers, Ted', 'Pozuelo-Rubio, Mercedes', 'Prak, Krisna', 'Prange, Reinhild', 'Prescott, Mark', 'Priault, Muriel', 'Prince, Sharon', 'Proia, Richard L', 'Proikas-Cezanne, Tassula', 'Prokisch, Holger', 'Promponas, Vasilis J', 'Przyklenk, Karin', 'Puertollano, Rosa', 'Pugazhenthi, Subbiah', 'Puglielli, Luigi', 'Pujol, Aurora', 'Puyal, Julien', 'Pyeon, Dohun', 'Qi, Xin', 'Qian, Wen-bin', 'Qin, Zheng-Hong', 'Qiu, Yu', 'Qu, Ziwei', 'Quadrilatero, Joe', 'Quinn, Frederick', 'Raben, Nina', 'Rabinowich, Hannah', 'Radogna, Flavia', 'Ragusa, Michael J', 'Rahmani, Mohamed', 'Raina, Komal', 'Ramanadham, Sasanka', 'Ramesh, Rajagopal', 'Rami, Abdelhaq', 'Randall-Demllo, Sarron', 'Randow, Felix', 'Rao, Hai', 'Rao, V Ashutosh', 'Rasmussen, Blake B', 'Rasse, Tobias M', 'Ratovitski, Edward A', 'Rautou, Pierre-Emmanuel', 'Ray, Swapan K', 'Razani, Babak', 'Reed, Bruce H', 'Reggiori, Fulvio', 'Rehm, Markus', 'Reichert, Andreas S', 'Rein, Theo', 'Reiner, David J', 'Reits, Eric', 'Ren, Jun', 'Ren, Xingcong', 'Renna, Maurizio', 'Reusch, Jane EB', 'Revuelta, Jose L', 'Reyes, Leticia', 'Rezaie, Alireza R', 'Richards, Robert I', 'Richardson, Des R', 'Richetta, Clémence', 'Riehle, Michael A', 'Rihn, Bertrand H', 'Rikihisa, Yasuko', 'Riley, Brigit E', 'Rimbach, Gerald', 'Rippo, Maria Rita', 'Ritis, Konstantinos', 'Rizzi, Federica', 'Rizzo, Elizete', 'Roach, Peter J', 'Robbins, Jeffrey', 'Roberge, Michel', 'Roca, Gabriela', 'Roccheri, Maria Carmela', 'Rocha, Sonia', 'Rodrigues, Cecilia MP', 'Rodríguez, Clara I', 'de Cordoba, Santiago Rodriguez', 'Rodriguez-Muela, Natalia', 'Roelofs, Jeroen', 'Rogov, Vladimir V', 'Rohn, Troy T', 'Rohrer, Bärbel', 'Romanelli, Davide', 'Romani, Luigina', 'Romano, Patricia Silvia', 'Roncero, M Isabel G', 'Rosa, Jose Luis', 'Rosello, Alicia', 'Rosen, Kirill V', 'Rosenstiel, Philip', 'Rost-Roszkowska, Magdalena', 'Roth, Kevin A', 'Roué, Gael', 'Rouis, Mustapha', 'Rouschop, Kasper M', 'Ruan, Daniel T', 'Ruano, Diego', 'Rubinsztein, David C', 'Rucker, Edmund B', 'Rudich, Assaf', 'Rudolf, Emil', 'Rudolf, Ruediger', 'Ruegg, Markus A', 'Ruiz-Roldan, Carmen', 'Ruparelia, Avnika Ashok', 'Rusmini, Paola', 'Russ, David W', 'Russo, Gian Luigi', 'Russo, Giuseppe', 'Russo, Rossella', 'Rusten, Tor Erik', 'Ryabovol, Victoria', 'Ryan, Kevin M', 'Ryter, Stefan W', 'Sabatini, David M', 'Sacher, Michael', 'Sachse, Carsten', 'Sack, Michael N', 'Sadoshima, Junichi', 'Saftig, Paul', 'Sagi-Eisenberg, Ronit', 'Sahni, Sumit', 'Saikumar, Pothana', 'Saito, Tsunenori', 'Saitoh, Tatsuya', 'Sakakura, Koichi', 'Sakoh-Nakatogawa, Machiko', 'Sakuraba, Yasuhito', 'Salazar-Roa, María', 'Salomoni, Paolo', 'Saluja, Ashok K', 'Salvaterra, Paul M', 'Salvioli, Rosa', 'Samali, Afshin', 'Sanchez, Anthony MJ', 'Sánchez-Alcázar, José A', 'Sanchez-Prieto, Ricardo', 'Sandri, Marco', 'Sanjuan, Miguel A', 'Santaguida, Stefano', 'Santambrogio, Laura', 'Santoni, Giorgio', 'dos Santos, Claudia Nunes', 'Saran, Shweta', 'Sardiello, Marco', 'Sargent, Graeme', 'Sarkar, Pallabi', 'Sarkar, Sovan', 'Sarrias, Maria Rosa', 'Sarwal, Minnie M', 'Sasakawa, Chihiro', 'Sasaki, Motoko', 'Sass, Miklos', 'Sato, Ken', 'Sato, Miyuki', 'Satriano, Joseph', 'Savaraj, Niramol', 'Saveljeva, Svetlana', 'Schaefer, Liliana', 'Schaible, Ulrich E', 'Scharl, Michael', 'Schatzl, Hermann M', 'Schekman, Randy', 'Scheper, Wiep', 'Schiavi, Alfonso', 'Schipper, Hyman M', 'Schmeisser, Hana', 'Schmidt, Jens', 'Schmitz, Ingo', 'Schneider, Bianca E', 'Schneider, E Marion', 'Schneider, Jaime L', 'Schon, Eric A', 'Schönenberger, Miriam J', 'Schönthal, Axel H', 'Schorderet, Daniel F', 'Schröder, Bernd', 'Schuck, Sebastian', 'Schulze, Ryan J', 'Schwarten, Melanie', 'Schwarz, Thomas L', 'Sciarretta, Sebastiano', 'Scotto, Kathleen', 'Scovassi, A Ivana', 'Screaton, Robert A', 'Screen, Mark', 'Seca, Hugo', 'Sedej, Simon', 'Segatori, Laura', 'Segev, Nava', 'Seglen, Per O', 'Seguí-Simarro, Jose M', 'Segura-Aguilar, Juan', 'Seki, Ekihiro', 'Seiliez, Iban', 'Sell, Christian', 'Semenkovich, Clay F', 'Semenza, Gregg L', 'Sen, Utpal', 'Serra, Andreas L', 'Serrano-Puebla, Ana', 'Sesaki, Hiromi', 'Setoguchi, Takao', 'Settembre, Carmine', 'Shacka, John J', 'Shajahan-Haq, Ayesha N', 'Shapiro, Irving M', 'Sharma, Shweta', 'She, Hua', 'Shen, C-K James', 'Shen, Chiung-Chyi', 'Shen, Han-Ming', 'Shen, Sanbing', 'Shen, Weili', 'Sheng, Rui', 'Sheng, Xianyong', 'Sheng, Zu-Hang', 'Shepherd, Trevor G', 'Shi, Junyan', 'Shi, Qiang', 'Shi, Qinghua', 'Shi, Yuguang', 'Shibutani, Shusaku', 'Shibuya, Kenichi', 'Shidoji, Yoshihiro', 'Shieh, Jeng-Jer', 'Shih, Chwen-Ming', 'Shimada, Yohta', 'Shimizu, Shigeomi', 'Shin, Dong Wook', 'Shinohara, Mari L', 'Shintani, Michiko', 'Shintani, Takahiro', 'Shioi, Tetsuo', 'Shirabe, Ken', 'Shiri-Sverdlov, Ronit', 'Shirihai, Orian', 'Shore, Gordon C', 'Shu, Chih-Wen', 'Shukla, Deepak', 'Sibirny, Andriy A', 'Sica, Valentina', 'Sigurdson, Christina J', 'Sigurdsson, Einar M', 'Sijwali, Puran Singh', 'Sikorska, Beata', 'Silveira, Wilian A', 'Silvente-Poirot, Sandrine', 'Silverman, Gary A', 'Simak, Jan', 'Simmet, Thomas', 'Simon, Anna Katharina', 'Simon, Hans-Uwe', 'Simone, Cristiano', 'Simons, Matias', 'Simonsen, Anne', 'Singh, Rajat', 'Singh, Shivendra V', 'Singh, Shrawan K', 'Sinha, Debasish', 'Sinha, Sangita', 'Sinicrope, Frank A', 'Sirko, Agnieszka', 'Sirohi, Kapil', 'Sishi, Balindiwe JN', 'Sittler, Annie', 'Siu, Parco M', 'Sivridis, Efthimios', 'Skwarska, Anna', 'Slack, Ruth', 'Slaninová, Iva', 'Slavov, Nikolai', 'Smaili, Soraya S', 'Smalley, Keiran SM', 'Smith, Duncan R', 'Soenen, Stefaan J', 'Soleimanpour, Scott A', 'Solhaug, Anita', 'Somasundaram, Kumaravel', 'Son, Jin H', 'Sonawane, Avinash', 'Song, Chunjuan', 'Song, Fuyong', 'Song, Hyun Kyu', 'Song, Ju-Xian', 'Song, Wei', 'Soo, Kai Y', 'Sood, Anil K', 'Soong, Tuck Wah', 'Soontornniyomkij, Virawudh', 'Sorice, Maurizio', 'Sotgia, Federica', 'Soto-Pantoja, David R', 'Sotthibundhu, Areechun', 'Sousa, Maria João', 'Spaink, Herman P', 'Span, Paul N', 'Spang, Anne', 'Sparks, Janet D', 'Speck, Peter G', 'Spector, Stephen A', 'Spies, Claudia D', 'Springer, Wolfdieter', 'Clair, Daret St', 'Stacchiotti, Alessandra', 'Staels, Bart', 'Stang, Michael T', 'Starczynowski, Daniel T', 'Starokadomskyy, Petro', 'Steegborn, Clemens', 'Steele, John W', 'Stefanis, Leonidas', 'Steffan, Joan', 'Stellrecht, Christine M', 'Stenmark, Harald', 'Stepkowski, Tomasz M', 'Stern, Stęphan T', 'Stevens, Craig', 'Stockwell, Brent R', 'Stoka, Veronika', 'Storchova, Zuzana', 'Stork, Björn', 'Stratoulias, Vassilis', 'Stravopodis, Dimitrios J', 'Strnad, Pavel', 'Strohecker, Anne Marie', 'Ström, Anna-Lena', 'Stromhaug, Per', 'Stulik, Jiri', 'Su, Yu-Xiong', 'Su, Zhaoliang', 'Subauste, Carlos S', 'Subramaniam, Srinivasa', 'Sue, Carolyn M', 'Suh, Sang Won', 'Sui, Xinbing', 'Sukseree, Supawadee', 'Sulzer, David', 'Sun, Fang-Lin', 'Sun, Jiaren', 'Sun, Jun', 'Sun, Shi-Yong', 'Sun, Yang', 'Sun, Yi', 'Sun, Yingjie', 'Sundaramoorthy, Vinod', 'Sung, Joseph', 'Suzuki, Hidekazu', 'Suzuki, Kuninori', 'Suzuki, Naoki', 'Suzuki, Tadashi', 'Suzuki, Yuichiro J', 'Swanson, Michele S', 'Swanton, Charles', 'Swärd, Karl', 'Swarup, Ghanshyam', 'Sweeney, Sean T', 'Sylvester, Paul W', 'Szatmari, Zsuzsanna', 'Szegezdi, Eva', 'Szlosarek, Peter W', 'Taegtmeyer, Heinrich', 'Tafani, Marco', 'Taillebourg, Emmanuel', 'Tait, Stephen WG', 'Takacs-Vellai, Krisztina', 'Takahashi, Yoshinori', 'Takáts, Szabolcs', 'Takemura, Genzou', 'Takigawa, Nagio', 'Talbot, Nicholas J', 'Tamagno, Elena', 'Tamburini, Jerome', 'Tan, Cai-Ping', 'Tan, Lan', 'Tan, Mei Lan', 'Tan, Ming', 'Tan, Yee-Joo', 'Tanaka, Keiji', 'Tanaka, Masaki', 'Tang, Daolin', 'Tang, Dingzhong', 'Tang, Guomei', 'Tanida, Isei', 'Tanji, Kunikazu', 'Tannous, Bakhos A', 'Tapia, Jose A', 'Tasset-Cuevas, Inmaculada', 'Tatar, Marc', 'Tavassoly, Iman', 'Tavernarakis, Nektarios', 'Taylor, Allen', 'Taylor, Graham S', 'Taylor, Gregory A', 'Taylor, J Paul', 'Taylor, Mark J', 'Tchetina, Elena V', 'Tee, Andrew R', 'Teixeira-Clerc, Fatima', 'Telang, Sucheta', 'Tencomnao, Tewin', 'Teng, Ba-Bie', 'Teng, Ru-Jeng', 'Terro, Faraj', 'Tettamanti, Gianluca', 'Theiss, Arianne L', 'Theron, Anne E', 'Thomas, Kelly Jean', 'Thomé, Marcos P', 'Thomes, Paul G', 'Thorburn, Andrew', 'Thorner, Jeremy', 'Thum, Thomas', 'Thumm, Michael', 'Thurston, Teresa LM', 'Tian, Ling', 'Till, Andreas', 'Ting, Jenny Pan-yun', 'Titorenko, Vladimir I', 'Toker, Lilach', 'Toldo, Stefano', 'Tooze, Sharon A', 'Topisirovic, Ivan', 'Torgersen, Maria Lyngaas', 'Torosantucci, Liliana', 'Torriglia, Alicia', 'Torrisi, Maria Rosaria', 'Tournier, Cathy', 'Towns, Roberto', 'Trajkovic, Vladimir', 'Travassos, Leonardo H', 'Triola, Gemma', 'Tripathi, Durga Nand', 'Trisciuoglio, Daniela', 'Troncoso, Rodrigo', 'Trougakos, Ioannis P', 'Truttmann, Anita C', 'Tsai, Kuen-Jer', 'Tschan, Mario P', 'Tseng, Yi-Hsin', 'Tsukuba, Takayuki', 'Tsung, Allan', 'Tsvetkov, Andrey S', 'Tu, Shuiping', 'Tuan, Hsing-Yu', 'Tucci, Marco', 'Tumbarello, David A', 'Turk, Boris', 'Turk, Vito', 'Turner, Robin FB', 'Tveita, Anders A', 'Tyagi, Suresh C', 'Ubukata, Makoto', 'Uchiyama, Yasuo', 'Udelnow, Andrej', 'Ueno, Takashi', 'Umekawa, Midori', 'Umemiya-Shirafuji, Rika', 'Underwood, Benjamin R', 'Ungermann, Christian', 'Ureshino, Rodrigo P.', 'Ushioda, Ryo', 'Uversky, Vladimir N', 'Uzcátegui, Néstor L', 'Vaccari, Thomas', 'Vaccaro, Maria I', 'Váchová, Libuše', 'Vakifahmetoglu-Norberg, Helin', 'Valdor, Rut', 'Valente, Enza Maria', 'Vallette, Francois', 'Valverde, Angela M', 'Van den Berghe, Greet', 'Van Den Bosch, Ludo', 'van den Brink, Gijs R', 'van der Goot, F Gisou', 'van der Klei, Ida J', 'van der Laan, Luc JW', 'van Doorn, Wouter G', 'van Egmond, Marjolein', 'van Golen, Kenneth L', 'Van Kaer, Luc', 'van Lookeren Campagne, Menno', 'Vandenabeele, Peter', 'Vandenberghe, Wim', 'Vanhorebeek, Ilse', 'Varela-Nieto, Isabel', 'Vasconcelos, M Helena', 'Vasko, Radovan', 'Vavvas, Demetrios G', 'Vega-Naredo, Ignacio', 'Velasco, Guillermo', 'Velentzas, Athanassios D', 'Velentzas, Panagiotis D', 'Vellai, Tibor', 'Vellenga, Edo', 'Vendelbo, Mikkel Holm', 'Venkatachalam, Kartik', 'Ventura, Natascia', 'Ventura, Salvador', 'Veras, Patrícia ST', 'Verdier, Mireille', 'Vertessy, Beata G', 'Viale, Andrea', 'Vidal, Michel', 'Vieira, Helena LA', 'Vierstra, Richard D', 'Vigneswaran, Nadarajah', 'Vij, Neeraj', 'Vila, Miquel', 'Villar, Margarita', 'Villar, Victor H', 'Villarroya, Joan', 'Vindis, Cécile', 'Viola, Giampietro', 'Viscomi, Maria Teresa', 'Vitale, Giovanni', 'Vogl, Dan T', 'Voitsekhovskaja, Olga V', 'von Haefen, Clarissa', 'von Schwarzenberg, Karin', 'Voth, Daniel E', 'Vouret-Craviari, Valérie', 'Vuori, Kristina', 'Vyas, Jatin M', 'Waeber, Christian', 'Walker, Cheryl Lyn', 'Walker, Mark J', 'Walter, Jochen', 'Wan, Lei', 'Wan, Xiangbo', 'Wang, Bo', 'Wang, Caihong', 'Wang, Chao-Yung', 'Wang, Chengshu', 'Wang, Chenran', 'Wang, Chuangui', 'Wang, Dong', 'Wang, Fen', 'Wang, Fuxin', 'Wang, Guanghui', 'Wang, Hai-jie', 'Wang, Haichao', 'Wang, Hong-Gang', 'Wang, Hongmin', 'Wang, Horng-Dar', 'Wang, Jing', 'Wang, Junjun', 'Wang, Mei', 'Wang, Mei-Qing', 'Wang, Pei-Yu', 'Wang, Peng', 'Wang, Richard C', 'Wang, Shuo', 'Wang, Ting-Fang', 'Wang, Xian', 'Wang, Xiao-jia', 'Wang, Xiao-Wei', 'Wang, Xin', 'Wang, Xuejun', 'Wang, Yan', 'Wang, Yanming', 'Wang, Ying', 'Wang, Ying-Jan', 'Wang, Yipeng', 'Wang, Yu', 'Wang, Yu Tian', 'Wang, Yuqing', 'Wang, Zhi-Nong', 'Wappner, Pablo', 'Ward, Carl', 'Ward, Diane McVey', 'Warnes, Gary', 'Watada, Hirotaka', 'Watanabe, Yoshihisa', 'Watase, Kei', 'Weaver, Timothy E', 'Weekes, Colin D', 'Wei, Jiwu', 'Weide, Thomas', 'Weihl, Conrad C', 'Weindl, Günther', 'Weis, Simone Nardin', 'Wen, Longping', 'Wen, Xin', 'Wen, Yunfei', 'Westermann, Benedikt', 'Weyand, Cornelia M', 'White, Anthony R', 'White, Eileen', 'Whitton, J Lindsay', 'Whitworth, Alexander J', 'Wiels, Joëlle', 'Wild, Franziska', 'Wildenberg, Manon E', 'Wileman, Tom', 'Wilkinson, Deepti Srinivas', 'Wilkinson, Simon', 'Willbold, Dieter', 'Williams, Chris', 'Williams, Katherine', 'Williamson, Peter R', 'Winklhofer, Konstanze F', 'Witkin, Steven S', 'Wohlgemuth, Stephanie E', 'Wollert, Thomas', 'Wolvetang, Ernst J', 'Wong, Esther', 'Wong, G William', 'Wong, Richard W', 'Wong, Vincent Kam Wai', 'Woodcock, Elizabeth A', 'Wright, Karen L', 'Wu, Chunlai', 'Wu, Defeng', 'Wu, Gen Sheng', 'Wu, Jian', 'Wu, Junfang', 'Wu, Mian', 'Wu, Min', 'Wu, Shengzhou', 'Wu, William KK', 'Wu, Yaohua', 'Wu, Zhenlong', 'Xavier, Cristina PR', 'Xavier, Ramnik J', 'Xia, Gui-Xian', 'Xia, Tian', 'Xia, Weiliang', 'Xia, Yong', 'Xiao, Hengyi', 'Xiao, Jian', 'Xiao, Shi', 'Xiao, Wuhan', 'Xie, Chuan-Ming', 'Xie, Zhiping', 'Xie, Zhonglin', 'Xilouri, Maria', 'Xiong, Yuyan', 'Xu, Chuanshan', 'Xu, Congfeng', 'Xu, Feng', 'Xu, Haoxing', 'Xu, Hongwei', 'Xu, Jian', 'Xu, Jianzhen', 'Xu, Jinxian', 'Xu, Liang', 'Xu, Xiaolei', 'Xu, Yangqing', 'Xu, Ye', 'Xu, Zhi-Xiang', 'Xu, Ziheng', 'Xue, Yu', 'Yamada, Takahiro', 'Yamamoto, Ai', 'Yamanaka, Koji', 'Yamashina, Shunhei', 'Yamashiro, Shigeko', 'Yan, Bing', 'Yan, Bo', 'Yan, Xianghua', 'Yan, Zhen', 'Yanagi, Yasuo', 'Yang, Dun-Sheng', 'Yang, Jin-Ming', 'Yang, Liu', 'Yang, Minghua', 'Yang, Pei-Ming', 'Yang, Peixin', 'Yang, Qian', 'Yang, Wannian', 'Yang, Wei Yuan', 'Yang, Xuesong', 'Yang, Yi', 'Yang, Ying', 'Yang, Zhifen', 'Yang, Zhihong', 'Yao, Meng-Chao', 'Yao, Pamela J', 'Yao, Xiaofeng', 'Yao, Zhenyu', 'Yao, Zhiyuan', 'Yasui, Linda S', 'Ye, Mingxiang', 'Yedvobnick, Barry', 'Yeganeh, Behzad', 'Yeh, Elizabeth S', 'Yeyati, Patricia L', 'Yi, Fan', 'Yi, Long', 'Yin, Xiao-Ming', 'Yip, Calvin K', 'Yoo, Yeong-Min', 'Yoo, Young Hyun', 'Yoon, Seung-Yong', 'Yoshida, Ken-Ichi', 'Yoshimori, Tamotsu', 'Young, Ken H', 'Yu, Huixin', 'Yu, Jane J', 'Yu, Jin-Tai', 'Yu, Jun', 'Yu, Li', 'Yu, W Haung', 'Yu, Xiao-Fang', 'Yu, Zhengping', 'Yuan, Junying', 'Yuan, Zhi-Min', 'Yue, Beatrice YJT', 'Yue, Jianbo', 'Yue, Zhenyu', 'Zacks, David N', 'Zacksenhaus, Eldad', 'Zaffaroni, Nadia', 'Zaglia, Tania', 'Zakeri, Zahra', 'Zecchini, Vincent', 'Zeng, Jinsheng', 'Zeng, Min', 'Zeng, Qi', 'Zervos, Antonis S', 'Zhang, Donna D', 'Zhang, Fan', 'Zhang, Guo', 'Zhang, Guo-Chang', 'Zhang, Hao', 'Zhang, Hong', 'Zhang, Hong', 'Zhang, Hongbing', 'Zhang, Jian', 'Zhang, Jian', 'Zhang, Jiangwei', 'Zhang, Jianhua', 'Zhang, Jing-pu', 'Zhang, Li', 'Zhang, Lin', 'Zhang, Lin', 'Zhang, Long', 'Zhang, Ming-Yong', 'Zhang, Xiangnan', 'Zhang, Xu Dong', 'Zhang, Yan', 'Zhang, Yang', 'Zhang, Yanjin', 'Zhang, Yingmei', 'Zhang, Yunjiao', 'Zhao, Mei', 'Zhao, Wei-Li', 'Zhao, Xiaonan', 'Zhao, Yan G', 'Zhao, Ying', 'Zhao, Yongchao', 'Zhao, Yu-xia', 'Zhao, Zhendong', 'Zhao, Zhizhuang J', 'Zheng, Dexian', 'Zheng, Xi-Long', 'Zheng, Xiaoxiang', 'Zhivotovsky, Boris', 'Zhong, Qing', 'Zhou, Guang-Zhou', 'Zhou, Guofei', 'Zhou, Huiping', 'Zhou, Shu-Feng', 'Zhou, Xu-jie', 'Zhu, Hongxin', 'Zhu, Hua', 'Zhu, Wei-Guo', 'Zhu, Wenhua', 'Zhu, Xiao-Feng', 'Zhu, Yuhua', 'Zhuang, Shi-Mei', 'Zhuang, Xiaohong', 'Ziparo, Elio', 'Zois, Christos E', 'Zoladek, Teresa', 'Zong, Wei-Xing', 'Zorzano, Antonio', 'Zughaier, Susu M']",,,,
,PMC,Modulating immunogenic properties of HIV-1 gp41 membrane-proximal external region by destabilizing six-helix bundle structure,http://dx.doi.org/10.1016/j.virol.2016.01.002,PMC4896743,,,"The C-terminal alpha-helix of gp41 membrane-proximal external region (MPER; (671)NWFDITNWLWYIK(683)) encompassing 4E10/10E8 epitopes is an attractive target for HIV-1 vaccine development. We previously reported that gp41-HR1-54Q, a trimeric protein comprised of the MPER in the context of a stable six-helix bundle (6HB), induced strong immune responses against the helix, but antibodies were directed primarily against the non-neutralizing face of the helix. To better target 4E10/10E8 epitopes, we generated four putative fusion intermediates by introducing double point mutations or deletions in the heptad repeat region 1 (HR1) that destabilize 6HB in varying degrees. One variant, HR1-Δ10-54K, elicited antibodies in rabbits that targeted W672, I675 and L679, which are critical for 4E10/10E8 recognition. Overall, the results demonstrated that altering structural parameters of 6HB can influence immunogenic properties of the MPER and antibody targeting. Further exploration of this strategy could allow development of immunogens that could lead to induction of 4E10/10E8-like antibodies.",,"['Banerjee, Saikat', 'Shi, Heliang', 'Habte, Habtom H.', 'Qin, Yali', 'Cho, Michael W.']",,,,
,PMC,Current strategies for protein production and purification enabling membrane protein structural biology,http://dx.doi.org/10.1139/bcb-2015-0143,PMC5752365,,,"Membrane proteins are still heavily underrepresented in the protein data bank (PDB) due to multiple bottlenecks. The typical low abundance of membrane proteins in their natural hosts makes it necessary to overexpress these proteins either in heterologous systems or through in vitro translation/cell-free expression. Heterologous expression of proteins, in turn, leads to multiple obstacles due to the unpredictability of compatibility of the target protein for expression in a given host. The highly hydrophobic and/or amphipathic nature of membrane proteins also leads to challenges in producing a homogeneous, stable, and pure sample for structural studies. Circumventing these hurdles has become possible through introduction of novel protein production protocols; efficient protein isolation and sample preparation methods; and, improvement in hardware and software for structural characterization. Combined, these advances have made the past 10–15 years very exciting and eventful for the field of membrane protein structural biology, with an exponential growth in the number of solved membrane protein structures. In this review, we focus on both the advances and diversity of protein production and purification methods that have allowed this growth in structural knowledge of membrane proteins through X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryo-electron microscopy (cryo-EM).",,"['Pandey, Aditya', 'Shin, Kyungsoo', 'Patterson, Robin E.', 'Liu, Xiang-Qin', 'Rainey, Jan K.']",,,,
,PMC,Host gene expression classifiers diagnose acute respiratory illness etiology,http://dx.doi.org/10.1126/scitranslmed.aad6873,PMC4905578,,,"Acute respiratory infections caused by bacterial or viral pathogens are among the most common reasons for seeking medical care. Despite improvements in pathogen-based diagnostics, most patients receive inappropriate antibiotics. Host response biomarkers offer an alternative diagnostic approach to direct antimicrobial use. This observational, cohort study determined whether host gene expression patterns discriminate non-infectious from infectious illness, and bacterial from viral causes of acute respiratory infection in the acute care setting. Peripheral whole blood gene expression from 273 subjects with community-onset acute respiratory infection (ARI) or non-infectious illness as well as 44 healthy controls was measured using microarrays. Sparse logistic regression was used to develop classifiers for bacterial ARI (71 probes), viral ARI (33 probes), or a non-infectious cause of illness (26 probes). Overall accuracy was 87% (238/273 concordant with clinical adjudication), which was more accurate than procalcitonin (78%, p<0.03) and three published classifiers of bacterial vs. viral infection (78-83%). The classifiers developed here externally validated in five publicly available datasets (AUC 0.90-0.99). A sixth publically available dataset included twenty-five patients with co-identification of bacterial and viral pathogens. Applying the ARI classifiers defined four distinct groups: a host response to bacterial ARI; viral ARI; co-infection; and neither a bacterial nor viral response. These findings create an opportunity to develop and utilize host gene expression classifiers as diagnostic platforms to combat inappropriate antibiotic use and emerging antibiotic resistance.",,"['Tsalik, Ephraim L.', 'Henao, Ricardo', 'Nichols, Marshall', 'Burke, Thomas', 'Ko, Emily R.', 'McClain, Micah T.', 'Hudson, Lori L.', 'Mazur, Anna', 'Freeman, Debra H.', 'Veldman, Tim', 'Langley, Raymond J.', 'Quackenbush, Eugenia B.', 'Glickman, Seth W.', 'Cairns, Charles B.', 'Jaehne, Anja K.', 'Rivers, Emanuel P.', 'Otero, Ronny M.', 'Zaas, Aimee K.', 'Kingsmore, Stephen F.', 'Lucas, Joseph', 'Fowler, Vance G.', 'Carin, Lawrence', 'Ginsburg, Geoffrey S.', 'Woods, Christopher W.']",,,,
,PMC,Genetic Immunization With In Vivo Dendritic Cell-targeting Liposomal DNA Vaccine Carrier Induces Long-lasting Antitumor Immune Response,http://dx.doi.org/10.1038/mt.2015.215,PMC4817821,,,"A major limiting factor retarding the clinical success of dendritic cell (DC)-based genetic immunizations (DNA vaccination) is the scarcity of biologically safe and effective carrier systems for targeting the antigen-encoded DNA vaccines to DCs under in vivo settings. Herein, we report on a potent, mannose receptor selective in vivo DC-targeting liposomes of a novel cationic amphiphile with mannose-mimicking shikimoyl head-group. Flow cytometric experiments with cells isolated from draining lymph nodes of mice s.c. immunized with lipoplexes of pGFP plasmid (model DNA vaccine) using anti-CD11c antibody-labeled magnetic beads revealed in vivo DC-targeting properties of the presently described liposomal DNA vaccine carrier. Importantly, s.c. immunizations of mice with electrostatic complex of the in vivo DC-targeting liposome and melanoma antigen-encoded DNA vaccine (p-CMV-MART1) induced long-lasting antimelanoma immune response (100 days post melanoma tumor challenge) with remarkable memory response (more than 6 months after the second tumor challenge). The presently described direct in vivo DC-targeting liposomal DNA vaccine carrier is expected to find future exploitations toward designing effective vaccines for various infectious diseases and cancers.",,"['Garu, Arup', 'Moku, Gopikrishna', 'Gulla, Suresh Kumar', 'Chaudhuri, Arabinda']",,,,
,PMC,CXCL13 promotes isotype-switched B cell accumulation to the central nervous system during viral encephalomyelitis,http://dx.doi.org/10.1016/j.bbi.2016.01.016,PMC4828287,,,"Elevated CXCL13 within the central nervous system (CNS) correlates with humoral responses in several neuroinflammatory diseases, yet its role is controversial. During coronavirus encephalomyelitis CXCL13 deficiency impaired CNS accumulation of memory B cells and antibody-secreting cells (ASC) but not naïve/early-activated B cells. However, despite diminished germinal center B cells and follicular helper T cells in draining lymph nodes, ASC in bone marrow and antiviral serum antibody were intact in the absence of CXCL13. The data demonstrate that CXCL13 is not essential in mounting effective peripheral humoral responses, but specifically promotes CNS accumulation of differentiated B cells.",,"['Phares, Timothy W.', 'DiSano, Krista D.', 'Stohlman, Stephen A.', 'Segal, Benjamin M.', 'Bergmann, Cornelia C.']",,,,
,PMC,Viral glycoproteins: biological role and application in diagnosis,http://dx.doi.org/10.1007/s13337-015-0293-5,PMC4758313,,,"The viruses that infect humans cause a huge global disease burden and produce immense challenge towards healthcare system. Glycoproteins are one of the major components of human pathogenic viruses. They have been demonstrated to have important role(s) in infection and immunity. Concomitantly high titres of antibodies against these antigenic viral glycoproteins have paved the way for development of novel diagnostics. Availability of appropriate biomarkers is necessary for advance diagnosis of infectious diseases especially in case of outbreaks. As human mobilization has increased manifold nowadays, dissemination of infectious agents became quicker that paves the need of rapid diagnostic system. In case of viral infection it is an emergency as virus spreads and mutates very fast. This review encircles the vast arena of viral glycoproteins, their importance in health and disease and their diagnostic applications.",,"['Banerjee, Nilotpal', 'Mukhopadhyay, Sumi']",,,,
,PMC,"Clinical Features, Virus Identification and Sinusitis as a Complication of Upper Respiratory Tract Illness in Children Ages 4-7 Years",http://dx.doi.org/10.1016/j.jpeds.2015.12.034,PMC4808614,,,"OBJECTIVE: To determine the rate of sinusitis complicating upper respiratory tract illnesses (URIs) for children in whom we prospectively identified the clinical, virologic, and epidemiologic characteristics of URIs in a population of 4 to 7 year old children followed for one year. STUDY DESIGN: This was an observational cohort study in two primary care pediatric practices in Madison, WI. Nasal samples were obtained during 4 asymptomatic surveillance visits and during symptomatic URIs. A polymerase chain reaction-based assay for 9 respiratory viruses was performed on nasal samples. A diagnosis of sinusitis was based on published criteria. RESULTS: 236 children ages 48-96 months were enrolled. A total of 327 URIs were characterized. The mean number of URIs per child was 1.3 (range 0-9) per year. Viruses were detected in 81% of URIs; rhinovirus (RV) was most common. Seventy-two percent of URIs were resolved clinically by the tenth day. RV-A and RV-C were detected more frequently at URI visits; RV-B was detected at the same rate for both asymptomatic surveillance visits and URI visits. Sinusitis was diagnosed in 8.8% of symptomatic URIs. Viruses were detected frequently (33%) in samples from asymptomatic children. CONCLUSIONS: Sinusitis occured in 8.8% of symptomatic URIs in our study. The virus most frequently detected with URIs in children was RV; RV-A and RV-C detection but not RV-B detection were associated with illness. Viruses, especially RV, are detected frequently in asymptomatic children. Most URIs have improved or resolved by the tenth day after onset. Children experienced a mean of 1.3 URIs per year which was lower than expected.",,"['DeMuri, Gregory P.', 'Gern, James E.', 'Moyer, Stacey C.', 'Lindstrom, Mary J.', 'Lynch, Susan V.', 'Wald, Ellen R.']",,,,
,PMC,Inducible Expression of CXCL1 within the Central Nervous System Amplifies Viral-Induced Demyelination,http://dx.doi.org/10.4049/jimmunol.1501802,PMC4742654,,,"The functional role of the ELR(+) chemokine CXCL1 in host defense and disease following infection of the CNS with the neurotropic JHM strain of mouse hepatitis virus (JHMV) was examined. Mice in which expression of CXCL1 is under the control of a tetracycline-inducible promoter active within glial fibrillary acidic protein–positive cells were generated and this allowed for selectively increasing CNS expression of CXCL1 in response to JHMV infection and evaluating the effects on neuroinflammation, control of viral replication, and demyelination. Inducible expression of CNS-derived CXCL1 resulted in increased levels of CXCL1 protein within the serum, brain, and spinal cord that correlated with increased frequency of Ly6G(+)CD11b(+) neutrophils present within the CNS. Elevated levels of CXCL1 did not influence the generation of virus-specific T cells, and there was no difference in control of JHMV replication compared with control mice, indicating that T cell infiltration into the CNS is CXCL1-independent. Sustained CXCL1 expression within the CNS resulted in increased mortality that correlated with elevated neutrophil infiltration, diminished numbers of mature oligodendrocytes, and an increase in the severity of demyelination. Neutrophil ablation in CXCL1-transgenic mice reduced the severity of demyelination in mice, arguing for a role for these cells in white matter damage. Collectively, these findings illustrate that sustained CXCL1 expression amplifies the severity of white matter damage and that neutrophils can contribute to this process in a model of viral-induced neurologic disease.",,"['Marro, Brett S.', 'Grist, Jonathan J.', 'Lane, Thomas E.']",,,,
,PMC,A Haploid Genetic Screen Identifies Heparan Sulfate Proteoglycans Supporting Rift Valley Fever Virus Infection,http://dx.doi.org/10.1128/JVI.02055-15,PMC4719632,,,"Rift Valley fever virus (RVFV) causes recurrent insect-borne epizootics throughout the African continent, and infection of humans can lead to a lethal hemorrhagic fever syndrome. Deep mutagenesis of haploid human cells was used to identify host factors required for RVFV infection. This screen identified a suite of enzymes involved in glycosaminoglycan (GAG) biogenesis and transport, including several components of the cis-oligomeric Golgi (COG) complex, one of the central components of Golgi complex trafficking. In addition, disruption of PTAR1 led to RVFV resistance as well as reduced heparan sulfate surface levels, consistent with recent observations that PTAR1-deficient cells exhibit altered Golgi complex morphology and glycosylation defects. A variety of biochemical and genetic approaches were utilized to show that both pathogenic and attenuated RVFV strains require GAGs for efficient infection on some, but not all, cell types, with the block to infection being at the level of virion attachment. Examination of other members of the Bunyaviridae family for GAG-dependent infection suggested that the interaction with GAGs is not universal among bunyaviruses, indicating that these viruses, as well as RVFV on certain cell types, employ additional unidentified virion attachment factors and/or receptors. IMPORTANCE Rift Valley fever virus (RVFV) is an emerging pathogen that can cause severe disease in humans and animals. Epizootics among livestock populations lead to high mortality rates and can be economically devastating. Human epidemics of Rift Valley fever, often initiated by contact with infected animals, are characterized by a febrile disease that sometimes leads to encephalitis or hemorrhagic fever. The global burden of the pathogen is increasing because it has recently disseminated beyond Africa, which is of particular concern because the virus can be transmitted by widely distributed mosquito species. There are no FDA-licensed vaccines or antiviral agents with activity against RVFV, and details of its life cycle and interaction with host cells are not well characterized. We used the power of genetic screening in human cells and found that RVFV utilizes glycosaminoglycans to attach to host cells. This furthers our understanding of the virus and informs the development of antiviral therapeutics.",,"['Riblett, Amber M.', 'Blomen, Vincent A.', 'Jae, Lucas T.', 'Altamura, Louis A.', 'Doms, Robert W.', 'Brummelkamp, Thijn R.', 'Wojcechowskyj, Jason A.']",,,,
,PMC,PACT- and RIG-I-Dependent Activation of Type I Interferon Production by a Defective Interfering RNA Derived from Measles Virus Vaccine,http://dx.doi.org/10.1128/JVI.02161-15,PMC4719617,,,"The live attenuated measles virus vaccine is highly immunostimulatory. Identification and characterization of its components that activate the innate immune response might provide new strategies and agents for the rational design and development of chemically defined adjuvants. In this study, we report on the activation of type I interferon (IFN) production by a defective interfering (DI) RNA isolated from the Hu-191 vaccine strain of measles virus. We found that the Hu-191 virus induced IFN-β much more potently than the Edmonston strain. In the search for IFN-inducing species in Hu-191, we identified a DI RNA specifically expressed by this strain. This DI RNA, which was of the copy-back type, was predicted to fold into a hairpin structure with a long double-stranded stem region of 206 bp, and it potently induced the expression of IFN-β. Its IFN-β-inducing activity was further enhanced when both cytoplasmic RNA sensor RIG-I and its partner, PACT, were overexpressed. On the contrary, this activity was abrogated in cells deficient in PACT or RIG-I. The DI RNA was found to be associated with PACT in infected cells. In addition, both the 5′-di/triphosphate end and the double-stranded stem region on the DI RNA were essential for its activation of PACT and RIG-I. Taken together, our findings support a model in which a viral DI RNA is sensed by PACT and RIG-I to initiate an innate antiviral response. Our work might also provide a foundation for identifying physiological PACT ligands and developing novel adjuvants or antivirals. IMPORTANCE The live attenuated measles virus vaccine is one of the most successful human vaccines and has largely contained the devastating impact of a highly contagious virus. Identifying the components in this vaccine that stimulate the host immune response and understanding their mechanism of action might help to design and develop better adjuvants, vaccines, antivirals, and immunotherapeutic agents. We identified and characterized a defective interfering RNA from the Hu-191 vaccine strain of measles virus which has safely been used in millions of people for many years. We further demonstrated that this RNA potently induces an antiviral immune response through cellular sensors of viral RNA known as PACT and RIG-I. Similar types of viral RNA that bind with and activate PACT and RIG-I might retain the immunostimulatory property of measles virus vaccines but would not induce adaptive immunity. They are potentially useful as chemically defined vaccine adjuvants, antivirals, and immunostimulatory agents.",,"['Ho, Ting-Hin', 'Kew, Chun', 'Lui, Pak-Yin', 'Chan, Chi-Ping', 'Satoh, Takashi', 'Akira, Shizuo', 'Jin, Dong-Yan', 'Kok, Kin-Hang']",,,,
,PMC,Impact of HIV-1 Membrane Cholesterol on Cell-Independent Lytic Inactivation and Cellular Infectivity,http://dx.doi.org/10.1021/acs.biochem.5b00936,PMC4988521,,,"Peptide triazole thiols (PTTs) have been found previously to bind to HIV-1 Env spike gp120 and cause irreversible virus inactivation by shedding gp120 and lytically releasing luminal capsid protein p24. Since the virions remain visually intact, lysis appears to occur via limited membrane destabilization. To better understand the PTT-triggered membrane transformation involved, we investigated the role of envelope cholesterol on p24 release by measuring the effect of cholesterol depletion using methyl beta-cyclodextrin (MβCD). An unexpected bell-shaped response of PTT-induced lysis to [MβCD] was observed, involving lysis enhancement at low [MβCD] vs loss of function at high [MβCD]. The impact of cholesterol depletion on PTT-induced lysis was reversed by adding exogenous cholesterol and other sterols that support membrane rafts, while sterols that do not support rafts induced only limited reversal. Cholesterol depletion appears to cause a reduced energy barrier to lysis as judged by decreased temperature dependence with MβCD. Enhancement/replenishment responses to [MβCD] also were observed for HIV-1 infectivity, consistent with a similar energy barrier effect in the membrane transformation of virus cell fusion. Overall, the results argue that cholesterol in the HIV-1 envelope is important for balancing virus stability and membrane transformation, and that partial depletion, while increasing infectivity, also makes the virus more fragile. The results also reinforce the argument that the lytic inactivation and infectivity processes are mechanistically related and that membrane transformations occurring during lysis can provide an experimental window to investigate membrane and protein factors important for HIV-1 cell entry.",,"['Sundaram, Ramalingam Venkat Kalyana', 'Li, Huiyuan', 'Bailey, Lauren', 'Rashad, Adel A.', 'Aneja, Rachna', 'Weiss, Karl', 'Huynh, James', 'Bastian, Arangaserry Rosemary', 'Papazoglou, Elisabeth', 'Abrams, Cameron', 'Wrenn, Steven', 'Chaiken, Irwin']",,,,
,PMC,Challenges with Diagnosing and Managing Sepsis in Older Adults,http://dx.doi.org/10.1586/14787210.2016.1135052,PMC4804629,,,"Sepsis in older adults has many challenges that affect rate of septic diagnosis, treatment, and monitoring parameters. Numerous age-related changes and comorbidities contribute to increased risk of infections in older adults, but also atypical symptomatology that delays diagnosis. Due to various pharmacokinetic/pharmacodynamic changes in the older adult, medications are absorbed, metabolized, and eliminated at different rates as compared to younger adults, which increases risk of adverse drug reactions due to use of drug therapy needed for sepsis management. This review provides information to aid in diagnosis as well as offers recommendations for monitoring and treating sepsis in the older adult population.",,"['Clifford, Kalin M.', 'Dy-Boarman, Eliza A.', 'Haase, Krystal K.', 'Maxvill, Kristen (Hesch)', 'Pass, Steven', 'Alvarez, Carlos A.']",,,,
,PMC,Autophagy Genes Enhance Murine Gammaherpesvirus 68 Reactivation From Latency by Preventing Virus-induced Systemic Inflammation,http://dx.doi.org/10.1016/j.chom.2015.12.010,PMC4714357,,,"Host genes that regulate systemic inflammation upon chronic viral infection are incompletely understood. Murine γ-herpesvirus 68 (MHV68) infection is characterized by latency in macrophages, and reactivation is inhibited by Interferon-γ (IFN-γ). Using a Lysozyme-M-cre (LysMcre) expression system, we show that deletion of autophagy-related (Atg) genes Fip200, beclin 1, Atg14, Atg16L1, Atg7, Atg3, and Atg5, in the myeloid compartment, inhibited MHV68 reactivation in macrophages. Atg5-deficiency did not alter reactivation from B cells, and effects on reactivation from macrophages were not explained by alterations in productive viral replication or the establishment of latency. Rather, chronic MHV68 infection triggered increased systemic inflammation, increased T cell production of IFN-γ and an IFN-γ-induced transcriptional signature in macrophages from Atg gene-deficient mice. The Atg5-related reactivation defect was partially reversed by neutralization of IFN-γ. Thus Atg genes in myeloid cells dampen virus-induced systemic inflammation, creating an environment that fosters efficient MHV68 reactivation from latency.",,"['Park, Sunmin', 'Buck, Michael D.', 'Desai, Chandni', 'Zhang, Xin', 'Loginicheva, Ekaterina', 'Martinez, Jennifer', 'Freeman, Michael L.', 'Saitoh, Tatsuya', 'Akira, Shizuo', 'Guan, Jun-Lin', 'He, You-Wen', 'Blackman, Marcia A.', 'Handley, Scott A.', 'Levine, Beth', 'Green, Douglas R.', 'Reese, Tiffany A.', 'Artyomov, Maxim N.', 'Virgin, Herbert W.']",,,,
,PMC,"Enhanced Humoral Response to Influenza Vaccine in Aged Mice with A Novel Adjuvant, rOv-ASP-1",http://dx.doi.org/10.1016/j.vaccine.2016.01.003,PMC4731280,,,"Immunization is the best way to prevent seasonal epidemics and pandemics of influenza. There are two kinds of influenza vaccines available in the United States: an inactivated vaccine (TIV) and an attenuated vaccine; however, only TIV is approved for immunization of the elderly population. While the aged population has the highest rate of influenza vaccination, the protective efficacy is low as evidenced by elderly individuals having the highest mortality associated with influenza. Recently, we reported that an adjuvant derived from the helminth parasite Onchocerca volvulus, named O. volvulus activation-associated secreted protein-1 (Ov-ASP-1), can significantly enhance the protective efficacy of an inactivated vaccine (TIV) in young adult mice. In the current study, we examined whether this recombinant Ov-ASP-1 (rOv-ASP-1) can enhance the efficacy of TIV in aged mice as well. While primary immunization with TIV alone produced only a low level of influenza-specific antibodies (total IgG, IgG1, and IgG2c) in aged mice, the antibody levels were significantly increased after immunization with TIV+rOv-ASP-1. More importantly, the level of the total IgG in aged mice administered TIV+rOv-ASP-1 was comparable to that of young adult mice immunized with TIV alone. Co-administration of rOv-ASP-1 induced a low level of crossreactive antibody and enhanced the protective efficacy of TIV in aged mice, reflected by significantly increased survival after challenge with a heterologous influenza virus. rOv-ASP-1 was also superior to the conventional adjuvant alum in inducing specific IgG after TIV immunization in aged mice, and in conferring protection after challenge. These results demonstrate that rOv-ASP-1 may serve as a potential adjuvant for influenza vaccine to improve the efficacy of protection in the elderly.",,"['Jiang, Jiu', 'Fisher, Erin M.', 'Concannon, Mark', 'Lustigman, Sara', 'Shen, Hao', 'Murasko, Donna M.']",,,,
,PMC,Systems biology: a tool for charting the antiviral landscape,http://dx.doi.org/10.1016/j.virusres.2016.01.005,PMC4902762,,,"The host antiviral programs that are initiated following viral infection form a dynamic and complex web of responses that we have collectively termed as “the antiviral landscape”. Conventional approaches to studying antiviral responses have primarily used reductionist systems to assess the function of a single or a limited subset of molecules. Systems biology is a holistic approach that considers the entire system as a whole, rather than individual components or molecules. Systems biology based approaches facilitate an unbiased and comprehensive analysis of the antiviral landscape, while allowing for the discovery of emergent properties that are missed by conventional approaches. The antiviral landscape can be viewed as a hierarchy of complexity, beginning at the whole organism level and progressing downward to isolated tissues, populations of cells, and single cells. In this review, we will discuss how systems biology has been applied to better understand the antiviral landscape at each of these layers. At the organismal level, the Collaborative Cross is an invaluable genetic resource for assessing how genetic diversity influences the antiviral responses. Whole tissue and isolated bulk cell transcriptomics serves as a critical tool for the comprehensive analysis of antiviral responses at both the tissue and cellular levels of complexity. Finally, new techniques in single cell analysis are emerging tools that will revolutionize our understanding of how individual cells within a bulk infected cell population contribute to the overall antiviral landscape.",,"['Bowen, James R.', 'Ferris, Martin T.', 'Suthar, Mehul S.']",,,,
,PMC,Induction of mucosal immunity through systemic immunization: Phantom or reality?,http://dx.doi.org/10.1080/21645515.2015.1114195,PMC4962944,,,"Generation of protective immunity at mucosal surfaces can greatly assist the host defense against pathogens which either cause disease at the mucosal epithelial barriers or enter the host through these surfaces. Although mucosal routes of immunization, such as intranasal and oral, are being intensely explored and appear promising for eliciting protective mucosal immunity in mammals, their application in clinical practice has been limited due to technical and safety related challenges. Most of the currently approved human vaccines are administered via systemic (such as intramuscular and subcutaneous) routes. Whereas these routes are acknowledged as being capable to elicit antigen-specific systemic humoral and cell-mediated immune responses, they are generally perceived as incapable of generating IgA responses or protective mucosal immunity. Nevertheless, currently licensed systemic vaccines do provide effective protection against mucosal pathogens such as influenza viruses and Streptococcus pneumoniae. However, whether systemic immunization induces protective mucosal immunity remains a controversial topic. Here we reviewed the current literature and discussed the potential of systemic routes of immunization for the induction of mucosal immunity.",,"['Su, Fei', 'Patel, Girishchandra B.', 'Hu, Songhua', 'Chen, Wangxue']",,,,
,PMC,"Capsule Commentary on Ganguli et al., Ebola Risk and Preparedness: A National Survey of Internists",http://dx.doi.org/10.1007/s11606-015-3570-5,PMC4762818,,,,,"Jackson, Jeffrey L.",,,,
,PMC,Prediction of Early Death in Adults with Relapsed or Refractory Acute Myeloid Leukemia,http://dx.doi.org/10.3109/10428194.2015.1135436,PMC5003083,,,,,"['Godwin, Colin D.', 'Othus, Megan', 'Powell, Morgan A.', 'Buckley, Sarah A.', 'Estey, Elihu H.', 'Walter, Roland B.']",,,,
,PMC,The chromosomal nature of LT-II enterotoxins solved: a lambdoid prophage encodes both LT-II and one of two novel pertussis-toxin-like toxin family members in type II enterotoxigenic Escherichia coli,http://dx.doi.org/10.1093/femspd/ftw001,PMC4957749,,,"Heat-labile enterotoxins (LT) of enterotoxigenic Escherichia coli (ETEC) are structurally and functionally related to cholera toxin (CT). LT-I toxins are plasmid-encoded and flanked by IS elements, while LT-II toxins of type II ETEC are chromosomally encoded with flanking genes that appear phage related. Here, I determined the complete genomic sequence of the locus for the LT-IIa type strain SA53, and show that the LT-IIa genes are encoded by a 51 239 bp lambdoid prophage integrated at the rac locus, the site of a defective prophage in E. coli K12 strains. Of 50 LT-IIa and LT-IIc, 46 prophages also encode one member of two novel two-gene ADP-ribosyltransferase toxin families that are both related to pertussis toxin, which I named eplBA or ealAB, respectively. The eplBA and ealAB genes are syntenic with the Shiga toxin loci in their lambdoid prophages of the enteric pathogen enterohemorrhagic E. coli. These novel AB(5) toxins show pertussis-toxin-like activity on tissue culture cells, and like pertussis toxin bind to sialic acid containing glycoprotein ligands. Type II ETEC are the first mucosal pathogens known to simultaneously produce two ADP-ribosylating toxins predicted to act on and modulate activity of both stimulatory and inhibitory alpha subunits of host cell heterotrimeric G-proteins.",,"Jobling, Michael G.",,,,
,PMC,Surveillance of the emerging enterovirus D68 in Canada: An evaluation,http://dx.doi.org/10.14745/ccdr.v42i01a01,PMC5864317,,,"BACKGROUND: In the fall of 2014, in response to outbreaks of an emerging respiratory pathogen enterovirus D68 (EV-D68) which affected mostly children, a rapid time-limited surveillance pilot for hospitalized cases was conducted in seven Canadian jurisdictions. OBJECTIVE: To evaluate whether the goals of the EV-D68 pilot were met and to determine the benefits of and lessons learned from a rapid-response surveillance system for emerging pathogens. METHODS: An evaluation survey was created and administered via a secure online link. All provinces and territories (PTs) and federal partners involved in the pilot were invited to complete one survey per jurisdiction (N=17). Proportions were calculated for responses to closed-ended questions and recurring themes were identified for open-ended questions. RESULTS: Fifty four percent (7/13) of PTs and 50% (2/4) of federal partners completed the survey. All four goals of the pilot were met to some degree. All respondents agreed that there were important benefits to rapid surveillance initiatives for emerging pathogens including the capacity to: better understand the epidemiological and clinical features as well as the public health risk of emerging pathogens (66.7%); inform public health action (66.7%); collaborate and avoid duplication of work (11.1%); test and develop jurisdictional capacity (11.1%); and inform future response efforts (11.1%). Receiving timely case summaries (preferably weekly) was identified as important for 88% of respondents. In terms of lessons learned, more than half of respondents (66.7%) indicated that current processes needed to be improved in order to facilitate rapid surveillance initiatives within and across jurisdictions including the need to develop data-sharing agreements and have pre-existing protocols. Important factors identified for a surveillance data reporting platform included: ease of functionality, data security, jurisdictional control, web-based and flexibility to meet changing surveillance needs. CONCLUSION: Evaluation results from the EV-D68 surveillance pilot will assist with future rapid surveillance initiatives. It is important that lessons learned be addressed prior to the emergence of the next emerging pathogen.",,"['Domingo, F Reyes', 'McMorris, O', 'Mersereau, T']",,,,
,PMC,Dengue in China: Comprehensive Phylogenetic Evaluation Reveals Evidence of Endemicity and Complex Genetic Diversity,http://dx.doi.org/10.4269/ajtmh.15-0546,PMC4710430,,,"Despite the increasing threat of dengue outbreaks in China, it is still considered as an imported disease and its introduction and/or circulation patterns remain obscure. On the basis of the most extensive phylogenetic analysis to date, we showed highly complex genetic diversity of dengue viruses (DENVs) in south China with up to 20 different clades/lineages from multiple serotypes co-circulating in the same year. Despite that most of these clades/lineages were resulted from imported cases, evidence of local persistence of DENV serotype 1 (DENV-1) was observed, indicating its potential endemicity in Guangdong province. This study, therefore, provided an overview of DENV genetic diversity and evolutionary dynamics in China, which will be useful for developing policies to prevent and control future dengue outbreaks in China.",,"['Chen, Rubing', 'Han, Guan-Zhu']",,,,
,PMC,Severe rhinovirus pneumonia in a young woman taking performance-enhancing drugs,http://dx.doi.org/10.1136/bcr-2015-213836,PMC4716367,,,"A 22-year-old woman presented to the emergency room of a local hospital with pleuritic chest pain. She regularly worked out and admitted to taking performance-enhancing drugs (PEDs). Clinical findings and further diagnostic work up revealed a diagnosis of perimyocarditis, and adequate therapy was initiated. During the course of the first day, the patient had to be intubated and mechanically ventilated. A diagnosis of bilateral pneumonia and acute respiratory distress syndrome (ARDS) due to an infection by rhinovirus spp was made. A smoking habit, the intense physical training and the use of PED's may have exacerbated the course of the viral pneumonia. After 12 days the patient could be extubated. The length of stay in the intensive care unit was 16 days. After hospital discharge, the patient went to a pulmonary rehabilitation facility for 2 weeks. The outcome was favourable and the patient resumed her strength and endurance training.",,"['Mayer, Kristina Nadine', 'Wyder, Daniel', 'Spasic, Danijela', 'Herren, Thomas']",,,,
,PMC,Macro Domain from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Is an Efficient ADP-ribose Binding Module: CRYSTAL STRUCTURE AND BIOCHEMICAL STUDIES,http://dx.doi.org/10.1074/jbc.M115.700542,PMC4777827,,,"The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) encodes the conserved macro domain within non-structural protein 3. However, the precise biochemical function and structure of the macro domain is unclear. Using differential scanning fluorimetry and isothermal titration calorimetry, we characterized the MERS-CoV macro domain as a more efficient adenosine diphosphate (ADP)-ribose binding module than macro domains from other CoVs. Furthermore, the crystal structure of the MERS-CoV macro domain was determined at 1.43-Å resolution in complex with ADP-ribose. Comparison of macro domains from MERS-CoV and other human CoVs revealed structural differences in the α1 helix alters how the conserved Asp-20 interacts with ADP-ribose and may explain the efficient binding of the MERS-CoV macro domain to ADP-ribose. This study provides structural and biophysical bases to further evaluate the role of the MERS-CoV macro domain in the host response via ADP-ribose binding but also as a potential target for drug design.",,"['Cho, Chao-Cheng', 'Lin, Meng-Hsuan', 'Chuang, Chien-Ying', 'Hsu, Chun-Hua']",,,,
,PMC,Hippuristanol - A potent steroid inhibitor of eukaryotic initiation factor 4A,http://dx.doi.org/10.1080/21690731.2015.1137381,PMC4909409,,,"Protein synthesis and its regulatory signaling pathways play essential roles in the initiation and maintenance of the cancer phenotype. Insight obtained over the last 3 decades on the mechanisms regulating translation in normal and transformed cells have revealed that perturbed control in cancer cells may offer an Achilles' heel for the development of novel anti-neoplastic agents. Several small molecule inhibitors have been identified and characterized that target translation initiation – more specifically, the rate-limiting step where ribosomes are recruited to mRNA templates. Among these, hippuristanol, a polyhydroxysteroid from the gorgonian Isis hippuris has been found to inhibit translation initiation by blocking the activity of eukaryotic initiation factor (eIF) 4A, an essential RNA helicase involved in this process. Herein, we highlight the biological properties of this compound, its potential development as an anti-cancer agent, and its use to validate eIF4A as an anti-neoplastic target.",,"['Cencic, Regina', 'Pelletier, Jerry']",,,,
,PMC,Dipeptidyl Peptidase 4 Distribution in the Human Respiratory Tract: Implications for the Middle East Respiratory Syndrome,http://dx.doi.org/10.1016/j.ajpath.2015.09.014,PMC4715219,,,"Dipeptidyl peptidase 4 (DPP4, CD26), a type II transmembrane ectopeptidase, is the receptor for the Middle Eastern respiratory syndrome coronavirus (MERS-CoV). MERS emerged in 2012 and has a high mortality associated with severe lung disease. A lack of autopsy studies from MERS fatalities has hindered understanding of MERS-CoV pathogenesis. We investigated the spatial and cellular localization of DPP4 to evaluate an association MERS clinical disease. DPP4 was rarely detected in the surface epithelium from nasal cavity to conducting airways with a slightly increased incidence in distal airways. DPP4 was also found in a subset of mononuclear leukocytes and in serous cells of submucosal glands. In the parenchyma, DPP4 was found principally in type I and II cells and alveolar macrophages and was also detected in vascular endothelium (eg, lymphatics) and pleural mesothelia. Patients with chronic lung disease, such as chronic obstructive pulmonary disease and cystic fibrosis, exhibited increased DPP4 immunostaining in alveolar epithelia (type I and II cells) and alveolar macrophages with similar trends in reactive mesothelia. This finding suggests that preexisting pulmonary disease could increase MERS-CoV receptor abundance and predispose individuals to MERS morbidity and mortality, which is consistent with current clinical observations. We speculate that the preferential spatial localization of DPP4 in alveolar regions may explain why MERS is characterized by lower respiratory tract disease.",,"['Meyerholz, David K.', 'Lambertz, Allyn M.', 'McCray, Paul B.']",,,,
,PMC,Newer therapeutics for hepatitis C,http://dx.doi.org/10.3978/j.issn.2305-5839.2015.10.06,PMC4731604,,,,,"['Poonia, Bhawna', 'Kottilil, Shyam']",,,,
,PMC,Outbreak investigation of porcine epidemic diarrhea in swine in Ontario,,PMC4677617,,,Porcine epidemic diarrhea virus was first diagnosed in Ontario in January of 2014. An outbreak investigation was conducted and it was hypothesized that feed containing spray-dried porcine plasma contaminated with the virus was a risk factor in the introduction and spread of the disease in Ontario.,,"['Pasma, Tim', 'Furness, Mary Catherine', 'Alves, David', 'Aubry, Pascale']",,,,
,PMC,Factors associated with development of Canine Infectious Respiratory Disease Complex (CIRDC) in dogs in 5 Canadian small animal clinics,,PMC4677608,,,"This study investigated the association between presence of respiratory pathogens and development of Canine Infectious Respiratory Disease Complex (CIRDC) in dogs in 5 Canadian small animal clinics. In total, 86 dogs were tested using a commercial PCR respiratory panel; 64 dogs were considered as cases and 22 were control dogs matched by veterinary clinic. No control animals (0/22) were positive for canine parainfluenza virus (CPIV), whereas 27/64 (42%) CIRDC cases were positive. Furthermore, 81% of case dogs tested positive for Mycoplasma cynos, compared with 73% of control dogs. Canine respiratory corona virus (CRCoV) was detected in no control dogs compared with 9.4% of clinical dogs. No animals were positive for any influenza virus type A present in the diagnostic panel. Presence of CPIV was associated (P < 0.01) with the occurrence of CIRDC after adjustment for demographic factors and presence of CRCoV (P = 0.09).",,"['Joffe, Daniel J.', 'Lelewski, Roxana', 'Weese, J. Scott', 'Mcgill-Worsley, Jamie', 'Shankel, Catharine', 'Mendonca, Sonia', 'Sager, Tara', 'Smith, Michael', 'Poljak, Zvonimir']",,,,
,PMC,Flow Cytometric Characterization of Antigen-Specific T Cells Based on RNA and Its Advantages in Detecting Infections and Immunological Disorders,http://dx.doi.org/10.1615/CritRevImmunol.2017018316,PMC5548664,,,"Fluorescence in situ hybridization coupled with flow cytometry (FISH-Flow) is a highly quantitative, high-throughput platform allowing precise quantification of total mRNA transcripts in single cells. In undiagnosed infections posing a significant health burden worldwide, such as latent tuberculosis or asymptomatic recurrent malaria, an important challenge is to develop accurate diagnostic tools. Antigen-specific T cells create a persistent memory to pathogens, making them useful for diagnosis of infection. Stimulation of memory response initiates T-cell transitions between functional states. Numerous studies have shown that changes in protein levels lag real-time T-cell transitions. However, analysis at the single-cell transcriptional level can determine the differences. FISH-Flow is a powerful tool with which to study the functional states of T-cell subsets and to identify the gene expression profiles of antigen-specific T cells during disease progression. Advances in instrumentation, fluorophores, and FISH methodologies will broaden and deepen the use of FISH-Flow, changing the immunological field by allowing determination of functional immune signatures at the mRNA level and the development of new diagnostic tools.",,"['Radford, Felix', 'Tyagi, Sanjay', 'Gennaro, Maria Laura', 'Pine, Richard', 'Bushkin, Yuri']",,,,
,PMC,Development of Small-molecule HIV Entry Inhibitors Specifically Targeting gp120 or gp41,,PMC4775441,,,"Human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein surface subunit gp120 and transmembrane subunit gp41 play important roles in HIV-1 entry, thus serving as key targets for the development of HIV-1 entry inhibitors. T20 peptide (enfuvirtide) is the first U.S. FDA-approved HIV entry inhibitor; however, its clinical application is limited by the lack of oral availability. Here, we have described the structure and function of the HIV-1 gp120 and gp41 subunits and reviewed advancements in the development of small-molecule HIV entry inhibitors specifically targeting these two Env glycoproteins. We then compared the advantages and disadvantages of different categories of HIV entry inhibitor candidates and further predicted the future trend of HIV entry inhibitor development.",,"['Lu, Lu', 'Yu, Fei', 'Cai, Lifeng', 'Debnath, Asim K.', 'Jiang, Shibo']",,,,
,PMC,Anti-Norovirus Therapeutics: A Patent Review (2010–2015),http://dx.doi.org/10.1517/13543776.2016.1153065,PMC4948123,,,"INTRODUCTION: Human noroviruses are the primary causative agents of acute gastroenteritis and are a pressing public health burden worldwide. There are currently no vaccines or small molecule therapeutics available for the treatment or prophylaxis of norovirus infections. An improved understanding of norovirus biology, as well as the pathogenic mechanisms underlying the disease, has provided the impetus for a range of intense exploratory drug discovery efforts targeting viral and host factors. AREAS COVERED: An overview of norovirus inhibitors disclosed in the patent literature (2010-present) and Clinicaltrials.gov is presented. The review is further enriched and supplemented by recent literature reports. EXPERT OPINION: Seminal discoveries made in recent years, including a better understanding of the pathobiology and life cycle of norovirus, the identification and targeting of multiple viral and host factors, the advent of a replicon system and a small animal model for the preclinical evaluation of lead compounds, and the availability of high resolution X-ray crystal structures that can be utilized in structure-based drug design and lead optimization campaigns, collectively suggest that a small molecule therapeutic and prophylactic for norovirus infection is likely to emerge in the not too distant future.",,"['Galasiti Kankanamalage, Anushka C.', 'Weerawarna, Pathum M.', 'Kim, Yunjeong', 'Chang, Kyeong-Ok', 'Groutas, William C.']",,,,
,PMC,"The Physiologic Effects of Isoflurane, Sevoflurane, and Hypothermia Used for Anesthesia in Neonatal Rats (Rattus norvegicus)",,PMC4747015,,,"Information regarding effective anesthetic regimens for neonatal rat pups is limited. Here we investigated whether isoflurane or sevoflurane anesthesia maintains physiologic parameters more consistently than does hypothermia anesthesia in neonatal rat pups. Rat pups (age, 4 d) were randomly assigned to receive isoflurane, sevoflurane, or hypothermia. Physiologic parameters monitored at 1, 5, 10, and 15 min included heart rate (HR), respiratory rate (RR), and oxygen saturation (%SpO(2)). Other parameters evaluated were loss and return of righting reflex, paw withdrawal reflex, and maternal acceptance. Corticosterone and glucose were sampled at 20 min and 24 h after anesthesia induction. Once a surgical plane of anesthesia was achieved, a skin incision was made on the right lateral thigh. After the procedure, all pups were accepted and cared for by their dam. Isoflurane- and sevoflurane-treated pups maintained higher HR, RR, %SpO(2), and glucose levels than did hypothermia-treated pups. For both the isoflurane and sevoflurane groups, HR and RR were significantly lower at 10 and 15 min after anesthesia than at 1 min. Compared with hypothermia, isoflurane and sevoflurane anesthesia provided shorter times to loss of and return of the righting reflex. Although corticosterone did not differ among the groups, glucose levels were higher at 20 min after anesthesia induction than at 24 h in all anesthetic groups. We conclude that both isoflurane and sevoflurane anesthesia maintain physiologic parameters (HR, RR, %SpO(2)) more consistently than does hypothermia anesthesia in 4-d-old rat pups.",,"['Huss, Monika K', 'Chum, Helen H', 'Chang, Angela G', 'Jampachairsi, Katechan', 'Pacharinsak, Cholawat']",,,,
,PMC,Analgesic Activity of Tramadol and Buprenorphine after Voluntary Ingestion by Rats (Rattus norvegicus),,PMC4747014,,,"Effective pain management for rats and mice is crucial due to the continuing increase in the use of these species in biomedical research. Here we used a recently validated operant orofacial pain assay to determine dose–response curves for buprenorphine and tramadol when mixed in nut paste and administered to male and female rats. Statistically significant analgesic doses of tramadol in nut paste included doses of 20, 30, and 40 mg/kg for female rats but only 40 mg/kg for male rats. For male rats receiving buprenorphine mixed in nut paste, a significant analgesic response was observed at 0.5 and 0.6 mg/kg. None of the doses tested produced a significant analgesic response in female rats. Our results indicate that at the doses tested, tramadol and buprenorphine produced an analgesic response in male rats. In female rats, tramadol shows a higher analgesic effect than buprenorphine. The analgesic effects observed 60 min after administration of the statistically significant oral doses of both drugs were similar to the analgesic effects of 0.03 mg/kg subcutaneous buprenorphine 30 min after administration. The method of voluntary ingestion could be effective, is easy to use, and would minimize stress to the rats during the immediate postoperative period.",,"['Taylor, Bryan F', 'Ramirez, Harvey E', 'Battles, August H', 'Andrutis, Karl A', 'Neubert, John K']",,,,
,PMC,Effect of 2 Bedding Materials on Ammonia Levels in Individually Ventilated Cages,,PMC4747007,,,"This study sought to identify an optimal rodent bedding and cage-change interval to establish standard procedures for the IVC in our rodent vivarium. Disposable cages were prefilled with either corncob or α-cellulose bedding and were used to house 2 adult Sprague–Dawley rats (experimental condition) or contained no animals (control). Rats were observed and intracage ammonia levels measured daily for 21 d. Intracage ammonia accumulation became significant by day 8 in experimental cages containing α-cellulose bedding, whereas experimental cages containing corncob bedding did not reach detectable levels of ammonia until day 14. In all 3 experimental cages containing α-cellulose, ammonia exceeded 100 ppm (our maximum acceptable limit) by day 11. Two experimental corncob cages required changing at days 16 and 17, whereas the remaining cage containing corncob bedding lasted the entire 21 d without reaching the 100-ppm ammonia threshold. These data suggests that corncob bedding provides nearly twice the service life of α-cellulose bedding in the IVC system.",,"['Koontz, Jason M', 'Kumsher, David M', 'III, Richard Kelly', 'Stallings, Jonathan D']",,,,
,PMC,Rat Breeding Parameters According to Floor Space Available in Cage,,PMC4747006,,,"The cage floor space recommended for a female rat with a litter is greater in the 8th edition of the Guide for the Care and Use of Laboratory Animals than in previous editions. As a result, research institutions using commonly available cages to house rats may not offer the recommended amount of space for a breeding pair and litter housed in the same cage. We evaluated breeding parameters in rats housed in cages with 143 in(2) (922.6 cm(2)) compared with 210 in(2) (1355 cm(2)) of floor space. Given the strains of rats typically used at our institution, a monogamous breeding pair and litter requires 164 in(2) (1058.1 cm(2)) of floor space according to the Guide. Pairs of breeding animals were housed in each type of cage; and average time between litters, number of litters born, percentage of litter weaned, numbers of pups born and weaned, and average weaning weights were evaluated. None of the breeding parameters evaluated differed according to the floor space of the cage in which the rats were housed.",,"['Allen, Kenneth P', 'Dwinell, Melinda R', 'Zappa, Allison M', 'Michaels, Andrea M', 'Murray, Kathleen M', 'Thulin, Joseph D']",,,,
,PMC,Rhinovirus-C detection in children presenting with acute respiratory infection to hospital in Brazil,http://dx.doi.org/10.1002/jmv.24300,PMC4682890,,,"INTRODUCTION: Human rhinovirus (RV) is a common cause of acute respiratory infection (ARI) in children. We aimed to characterise the clinical and demographic features associated with different RV species detected in children attending hospital with ARI, from low-income families in North-east Brazil. METHODS: Nasopharyngeal aspirates were collected from 630 children <5years with ARI. Clinical diagnosis and disease severity were also recorded. Samples were analysed by multiplex PCR for 18 viral and atypical bacterial pathogens; RV positive samples underwent partial sequencing to determine species and type. RESULTS: RV was the fourth commonest pathogen accounting for 18.7% of pathogens detected. RV was commonly detected in children with bronchiolitis, pneumonia and asthma/episodic viral wheeze (EVW). Species and type were assigned in 112 cases (73% RV-A; 27% RV-C; 0% RV-B). Generally, there were no differences in clinical or demographic characteristics between those infected with RV-A and RV-C. However, in children with asthma/EVW, RV-C was detected relatively more frequently than RV-A (23% vs 5%; p=0.04). CONCLUSIONS: Our findings highlight RV as a potentially important pathogen in this setting. Generally, clinical and demographic features were similar in children in whom RV A and C species were detected. However, RV-C was more frequently found in children with asthma/EVW than RV-A.",,"['Fawkner-Corbett, DW', 'Khoo, SK', 'Duarte, MC', 'Bezerra, PGM', 'Bochkov, YA', 'Gern, JE', 'Le Souef, PN', 'McNamara, PS']",,,,
,PMC,Face shields for infection control: A review,http://dx.doi.org/10.1080/15459624.2015.1095302,PMC5015006,,,"Face shields are personal protective equipment devices that are used by many workers (e.g., medical, dental, veterinary) for protection of the facial area and associated mucous membranes (eyes, nose, mouth) from splashes, sprays, and spatter of body fluids. Face shields are generally not used alone, but in conjunction with other protective equipment and are therefore classified as adjunctive personal protective equipment. Although there are millions of potential users of face shields, guidelines for their use vary between governmental agencies and professional societies and little research is available regarding their efficacy.",,"Roberge, Raymond J.",,,,
,PMC,Role of preprocedural rinse and high volume evacuator in reducing bacterial contamination in bioaerosols,http://dx.doi.org/10.4103/0973-029X.180931,PMC4860938,27194863,CC BY-NC-SA,"CONTEXT: Microbial contamination, which occurs during dental procedures, has been a potential threat to dental professionals and individuals. There has been a growing concern over the role of bioaerosols in spread of various airborne infections and also to reduce the risk of bioaerosol contamination. AIMS: This study was to analyze the number of colony forming units (CFUs) in bioaerosols generated during ultrasonic scaling procedure as well as to evaluate the efficacy of chlorhexidine 0.12% (CHX) preprocedural mouth rinse and high volume evacuator (HVE) in minimizing the bioaerosol contamination. METHODS: About 45 individuals were divided into three Groups A, B and C. These groups underwent ultrasonic scaling before and after the use of CHX (0.12%), HVE and combination of CHX (0.12%) and HVE. Bioaerosols were collected on blood agar plates which were incubated at 37°C for 48 h, and the CFUs were counted with manual colony counting device. A comparison was also done between A versus B, B versus C and A versus C groups. STATISTICAL ANALYSIS USED: Student's t-test. RESULTS: We found a significant reduction in the CFUs when CHX (0.12%) preprocedural rinse (P < 0), or HVE (P < 0.001) or combination of both CHX (0.12%) and HVE were employed (P < 0.001). Maximum reduction in CFUs was observed when CHX (0.12%) and HVE were used in combination as compared to their individual use. A moderate significance was seen between A versus C groups but not with B versus C groups and A versus B groups. CONCLUSION: From our study, we conclude that individual methods such as CHX (0.12%) and HVE were useful to reduce the dental bioaerosols; however, combination of both CHX (0.12%) and HVE is more efficient to reduce dental bioaerosols than individual method.",2016 Jan-Apr,"['Narayana, TV', 'Mohanty, Leeky', 'Sreenath, G', 'Vidhyadhari, Pavani']",J Oral Maxillofac Pathol,,,
,PMC,Role of immune aging in susceptibility to West Nile virus,http://dx.doi.org/10.1007/978-1-4939-3670-0_18,PMC4941816,,,,,"['Yao, Yi', 'Montgomery, Ruth R.']",,,,
,PMC,EBOLA: A PUBLIC HEALTH AND LEGAL PERSPECTIVE(),,PMC4920479,,,,,"['Markey, Melissa', 'Ransom, Montrece M.', 'Sunshine, Gregory']",,,,
,PMC,"Comparing Methods for Estimating the Burden of Pandemic Infectious Disease: The Case of the Second Wave of Pandemic H1N1 in Forsyth County, N.C",http://dx.doi.org/10.18043/ncm.77.1.15,PMC4714769,,,"BACKGROUND: Understanding the burden of influenza A(H1N1)pdm09 virus during the second wave of 2009–2010 is important for future pandemic planning. RESEARCH DESIGN: Persons who presented to the emergency department (ED) or were hospitalized with fever and/or acute respiratory symptoms at the academic medical center within Forsyth County, NC were prospectively enrolled with nasal/throat swab testing for influenza A(H1N1)pdm09. Laboratory-confirmed cases of influenza A(H1N1)pdm09 virus identified through active surveillance were compared by capture-recapture analysis to those identified through independent, passive surveillance (physician-ordered influenza testing). This approach estimated the total cases, including those not captured by either surveillance system. A second analysis estimated the total influenza A(H1N1)pdm09 cases by multiplying weekly influenza percentages from active surveillance by weekly counts of influenza-associated discharge diagnoses from administrative data. Market share adjustments were used to estimate influenza A(H1N1)pdm09 virus ED visits or hospitalizations per 1000 residents overall. RESULTS: Capture-recapture analysis estimated 753 residents (95% confidence interval, 424–2,735) were seen with influenza A(H1N1)pdm09 virus within the academic medical center from September 2009 through mid-April 2010; this result yielded an estimated 4.7 (95% confidence interval 2.6–16.9) influenza A(H1N1)pdm09 virus ED visits or hospitalizations per 1000 residents. Similarly, 708 visits were estimated using weekly influenza percentages and influenza-associated discharge diagnoses, yielding an estimated 4.4 influenza A(H1N1)pdm09 virus ED visits or hospitalizations per 1000 residents. CONCLUSION: This study demonstrates that the burden of influenza A(H1N1)pdm09 virus in ED and inpatient settings by capture-recapture analysis was 4–5 per 1000 residents and ~8-fold higher than that detected by physician-ordered influenza testing.",,"['Peters, Timothy R.', 'Snively, Beverly M.', 'Suerken, Cynthia K.', 'Bischoff, Werner', 'Vannoy, Lauren', 'Blakeney, Elizabeth', 'Bischoff, Tammy', 'Palavecino, Elizabeth', 'Sherertz, Robert', 'Poehling, Katherine A.']",,,,
,PMC,Insights into Antimicrobial Peptides from Spiders and Scorpions,,PMC4967028,,,"The venoms of spiders and scorpions contain a variety of chemical compounds. Antimicrobial peptides (AMPs) from these organisms were first discovered in the 1990s. As of May 2015, there were 42 spider’s and 63 scorpion’s AMPs in the Antimicrobial Peptide Database (http://aps.unmc.edu/AP). These peptides have demonstrated broad or narrow-spectrum activities against bacteria, fungi, viruses, and parasites. In addition, they can be toxic to cancer cells, insects and erythrocytes. To provide insight into such an activity spectrum, this article discusses the discovery, classification, structure and activity relationships, bioinformatics analysis, and potential applications of spider and scorpion AMPs. Our analysis reveals that, in the case of linear peptides, spiders use both glycine-rich and helical peptide models for defense, whereas scorpions use two distinct helical peptide models with different amino acid compositions to exert the observed antimicrobial activities and hemolytic toxicity. Our structural bioinformatics study improves the knowledge in the field and can be used to design more selective peptides to combat tumors, parasites, and viruses.",,"['Wang, Xiuqing', 'Wang, Guangshun']",,,,
,PMC,Long-range RNA pairings contribute to mutually exclusive splicing,http://dx.doi.org/10.1261/rna.053314.115,PMC4691838,,,"Mutually exclusive splicing is an important means of increasing the protein repertoire, by which the Down's syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 different isoforms in Drosophila melanogaster. However, the regulatory mechanisms remain obscure due to the complexity of the Dscam exon cluster. Here, we reveal a molecular model for the regulation of the mutually exclusive splicing of the serpent pre-mRNA based on competition between upstream and downstream RNA pairings. Such dual RNA pairings confer fine tuning of the inclusion of alternative exons. Moreover, we demonstrate that the splicing outcome of alternative exons is mediated in relative pairing strength-correlated mode. Combined comparative genomics analysis and experimental evidence revealed similar bidirectional structural architectures in exon clusters 4 and 9 of the Dscam gene. Our findings provide a novel mechanistic framework for the regulation of mutually exclusive splicing and may offer potentially applicable insights into long-range RNA–RNA interactions in gene regulatory networks.",,"['Yue, Yuan', 'Yang, Yun', 'Dai, Lanzhi', 'Cao, Guozheng', 'Chen, Ran', 'Hong, Weiling', 'Liu, Baoping', 'Shi, Yang', 'Meng, Yijun', 'Shi, Feng', 'Xiao, Mu', 'Jin, Yongfeng']",,,,
,PMC,Cytoplasmic poly(A) binding protein-1 binds to genomically encoded sequences within mammalian mRNAs,http://dx.doi.org/10.1261/rna.053447.115,PMC4691835,,,"The functions of the major mammalian cytoplasmic poly(A) binding protein, PABPC1, have been characterized predominantly in the context of its binding to the 3′ poly(A) tails of mRNAs. These interactions play important roles in post-transcriptional gene regulation by enhancing translation and mRNA stability. Here, we performed transcriptome-wide CLIP-seq analysis to identify additional PABPC1 binding sites within genomically encoded mRNA sequences that may impact on gene regulation. From this analysis, we found that PABPC1 binds directly to the canonical polyadenylation signal in thousands of mRNAs in the mouse transcriptome. PABPC1 binding also maps to translation initiation and termination sites bracketing open reading frames, exemplified most dramatically in replication-dependent histone mRNAs. Additionally, a more restricted subset of PABPC1 interaction sites comprised A-rich sequences within the 5′ UTRs of mRNAs, including Pabpc1 mRNA itself. Functional analyses revealed that these PABPC1 interactions in the 5′ UTR mediate both auto- and trans-regulatory translational control. In total, these findings reveal a repertoire of PABPC1 binding that is substantially broader than previously recognized with a corresponding potential to impact and coordinate post-transcriptional controls critical to a broad array of cellular functions.",,"['Kini, Hemant K.', 'Silverman, Ian M.', 'Ji, Xinjun', 'Gregory, Brian D.', 'Liebhaber, Stephen A.']",,,,
,PMC,Considerations for Use of Investigational Drugs in Public Health Emergencies,http://dx.doi.org/10.1177/2168479016680253,PMC5486404,,,"The paradigm for the use of investigational drugs in public health emergencies has been recently tested to prevent and treat highly infectious and lethal diseases. Examples include the successful implementation of vaccine and therapeutic clinical trials during the recent Ebola outbreak in West Africa. On the other end of the spectrum was the Emergency Use Authorization (EUA) of peramivir in the treatment of H1N1 influenza virus that did not provide an opportunity to collect data or understand the effectiveness of the EUA program. Between the gold standard of a randomized controlled clinical trial and the problems associated with EUAs are the domain of expanded access protocols that may provide an avenue to make products available while awaiting licensure. This paper will examine the regulatory pathways in the United States (US) for the use of investigational drugs in a public health emergency as well as considerations when making these products available outside the US. Descriptions of the applications of the various approaches will be presented. Regardless of the pathway chosen, public health and clinical research planners need to work together to consider several factors associated with the respective options and maintain a goal of working toward the collection of data to support licensure before faced with future outbreaks. Finally, this paper will consider the lessons learned from public health response in the context of investigational drugs in other diseases where “right to try laws” may pose opportunities, as well as challenges.",,"['Kirchoff, Matthew Carl', 'Pierson, Jerome F.']",,,,
,PMC,High Prevalence of Mycoplasma faucium DNA in the Human Oropharynx,http://dx.doi.org/10.1128/JCM.02068-15,PMC4702739,,,"Mycoplasma faucium has recently been associated with brain abscesses and seems to originate from the mouth. We evaluated its prevalence by quantitative real-time PCR (qPCR) in the oropharynxes of 644 subjects and found that 25% harbored M. faucium, probably constituting the gateway for entrance of the bacteria into cerebral abscesses.",,"['Edouard, Sophie', 'Courtois, Gaëlle Denis', 'Gautret, Philippe', 'Jouve, Jean-Luc', 'Minodier, Philippe', 'Noël, Guilhem', 'Roch, Antoine', 'Brouqui, Philippe', 'Stein, Andreas', 'Drancourt, Michel', 'Fournier, Pierre-Edouard', 'Raoult, Didier']",,,,
,PMC,Zoonotic Potential of Simian Arteriviruses,http://dx.doi.org/10.1128/JVI.01433-15,PMC4702702,,,"Wild nonhuman primates are immediate sources and long-term reservoirs of human pathogens. However, ethical and technical challenges have hampered the identification of novel blood-borne pathogens in these animals. We recently examined RNA viruses in plasma from wild African monkeys and discovered several novel, highly divergent viruses belonging to the family Arteriviridae. Close relatives of these viruses, including simian hemorrhagic fever virus, have caused sporadic outbreaks of viral hemorrhagic fever in captive macaque monkeys since the 1960s. However, arterivirus infection in wild nonhuman primates had not been described prior to 2011. The arteriviruses recently identified in wild monkeys have high sequence and host species diversity, maintain high viremia, and are prevalent in affected populations. Taken together, these features suggest that the simian arteriviruses may be “preemergent” zoonotic pathogens. If not, this would imply that biological characteristics of RNA viruses thought to facilitate zoonotic transmission may not, by themselves, be sufficient for such transmission to occur.",,"['Bailey, Adam L.', 'Lauck, Michael', 'Sibley, Samuel D.', 'Friedrich, Thomas C.', 'Kuhn, Jens H.', 'Freimer, Nelson B.', 'Jasinska, Anna J.', 'Phillips-Conroy, Jane E.', 'Jolly, Clifford J.', 'Marx, Preston A.', 'Apetrei, Cristian', 'Rogers, Jeffrey', 'Goldberg, Tony L.', ""O'Connor, David H.""]",,,,
,PMC,Targeting Swine Leukocyte Antigen Class I Molecules for Proteasomal Degradation by the nsp1α Replicase Protein of the Chinese Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Strain JXwn06,http://dx.doi.org/10.1128/JVI.02307-15,PMC4702659,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) is a critical pathogen of swine, and infections by this virus often result in delayed, low-level induction of cytotoxic T lymphocyte (CTL) responses in pigs. Here, we report that a Chinese highly pathogenic PRRSV strain possessed the ability to downregulate swine leukocyte antigen class I (SLA-I) molecules on the cell surface of porcine alveolar macrophages and target them for degradation in a manner that was dependent on the ubiquitin-proteasome system. Moreover, we found that the nsp1α replicase protein contributed to this property of PRRSV. Further mutagenesis analyses revealed that this function of nsp1α required the intact molecule, including the zinc finger domain, but not the cysteine protease activity. More importantly, we found that nsp1α was able to interact with both chains of SLA-I, a requirement that is commonly needed for many viral proteins to target their cellular substrates for proteasomal degradation. Together, our findings provide critical insights into the mechanisms of how PRRSV might evade cellular immunity and also add a new role for nsp1α in PRRSV infection. IMPORTANCE PRRSV infections often result in delayed, low-level induction of CTL responses in pigs. Deregulation of this immunity is thought to prevent the virus from clearance in an efficient and timely manner, contributing to persistent infections in swineherds. Our studies in this report provide critical insight into the mechanism of how PRRSV might evade CTL responses. In addition, our findings add a new role for nsp1α, a critical viral factor involved in antagonizing host innate immunity.",,"['Du, Jige', 'Ge, Xinna', 'Liu, Ying', 'Jiang, Ping', 'Wang, Zhe', 'Zhang, Ruimin', 'Zhou, Lei', 'Guo, Xin', 'Han, Jun', 'Yang, Hanchun']",,,,
,PMC,Molecular mechanisms for enhanced DNA vaccine immunogenicity,http://dx.doi.org/10.1586/14760584.2016.1124762,PMC4955855,,,"In the two decades since their initial discovery, DNA vaccines technologies have come a long way. Unfortunately, when applied to human subjects inadequate immunogenicity is still the biggest challenge for practical DNA vaccine use. Many different strategies have been tested in preclinical models to address this problem, including novel plasmid vectors and codon optimization to enhance antigen expression, new gene transfection systems or electroporation to increase delivery efficiency, protein or live virus vector boosting regimens to maximise immune stimulation, and formulation of DNA vaccines with traditional or molecular adjuvants. Better understanding of the mechanisms of action of DNA vaccines has also enabled better use of the intrinsic host response to DNA to improve vaccine immunogenicity. This review summarizes recent advances in DNA vaccine technologies and related intracellular events and how these might impact on future directions of DNA vaccine development.",,"['Li, Lei', 'Petrovsky, Nikolai']",,,,
,PMC,The Microbiome in Cystic Fibrosis,http://dx.doi.org/10.1016/j.ccm.2015.10.003,PMC5154676,,,"Observations from studies during the last decade have changed our conventional view of CF microbiology, which has traditionally focused on a relatively limited suite of opportunistic bacterial pathogens. Much of this change has been driven by the application of next-generation DNA sequencing technology to better assess the microbiota in CF respiratory specimens. We now appreciate that CF airways typically harbor complex microbial communities, and that changes in the structure and activity of these communities has bearing on patient clinical condition and lung disease progression. Recently, studies of gut microbiota suggest that the disordered bacterial ecology of the CF gastrointestinal tract is associated with lung pathology. Although challenges to a more complete understanding of the role lung and gut microbiota play in disease progression remain, these new insights provide exciting prospects to reconsider clinical management of CF.",,"['Huang, Yvonne J.', 'LiPuma, John J.']",,,,
,PMC,"Hepatitis B and C virus-induced hepatitis: Apoptosis, autophagy, and unfolded protein response",http://dx.doi.org/10.3748/wjg.v21.i47.13225,PMC4679754,,,"AIM: To investigate the co-incidence of apoptosis, autophagy, and unfolded protein response (UPR) in hepatitis B (HBV) and C (HCV) infected hepatocytes. METHODS: We performed immunofluorescence confocal microscopy on 10 liver biopsies from HBV and HCV patients and tissue microarrays of HBV positive liver samples. We used specific antibodies for LC3β, cleaved caspase-3, BIP (GRP78), and XBP1 to detect autophagy, apoptosis and UPR, respectively. Anti-HCV NS3 and anti-HBs antibodies were also used to confirm infection. We performed triple blind counting of events to determine the co-incidence of autophagy (LC3β punctuate), apoptosis (cleaved caspase-3), and unfolded protein response (GRP78) with HBV and HCV infection in hepatocytes. All statistical analyses were performed using SPSS software for Windows (Version 16 SPSS Inc, Chicago, IL, United States). P-values < 0.05 were considered statistically significant. Statistical analyses were performed with Mann-Whitney test to compare incidence rates for autophagy, apoptosis, and UPR in HBV- and HCV-infected cells and adjacent non-infected cells. RESULTS: Our results showed that infection of hepatocytes with either HBV and HCV induces significant increase (P < 0.001) in apoptosis (cleavage of caspase-3), autophagy (LC3β punctate), and UPR (increase in GRP78 expression) in the HCV- and HBV-infected cells, as compared to non-infected cells of the same biopsy sections. Our tissue microarray immunohistochemical expression analysis of LC3β in HBV(Neg) and HBV(Pos) revealed that majority of HBV-infected hepatocytes display strong positive staining for LC3β. Interestingly, although XBP splicing in HBV-infected cells was significantly higher (P < 0.05), our analyses show a slight increase of XBP splicing was in HCV-infected cells (P > 0.05). Furthermore, our evaluation of patients with HBV and HCV infection based on stage and grade of the liver diseases revealed no correlation between these pathological findings and induction of apoptosis, autophagy, and UPR. CONCLUSION: The results of this study indicate that HCV and HBV infection activates apoptosis, autophagy and UPR, but slightly differently by each virus. Further studies are warranted to elucidate the interconnections between these pathways in relation to pathology of HCV and HBV in the liver tissue.",,"['Yeganeh, Behzad', 'Rezaei Moghadam, Adel', 'Alizadeh, Javad', 'Wiechec, Emilia', 'Alavian, Seyed Moayed', 'Hashemi, Mohammad', 'Geramizadeh, Bita', 'Samali, Afshin', 'Bagheri Lankarani, Kamran', 'Post, Martin', 'Peymani, Payam', 'Coombs, Kevin M', 'Ghavami, Saeid']",,,,
,PMC,Comparison of respiratory virus shedding by conventional and molecular testing methods in patients with haematological malignancy,http://dx.doi.org/10.1016/j.cmi.2015.12.012,PMC4994888,,,"Respiratory viruses (RV) are a leading cause of infection-related morbidity and mortality for patients undergoing treatment for cancer. This analysis compared duration of RV shedding as detected by culture and PCR among patients in a high-risk oncology setting (adult patients with haematological malignancy and/or stem cell transplant and all paediatric oncology patients) and determined risk factors for extended shedding. RV infections due to influenza virus, parainfluenza virus (PIV), human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) from two study periods—January 2009–September 2011 (culture-based testing) and September 2011–April 2013 (PCR-based testing)—were reviewed retrospectively. Data were collected from patients in whom re-testing for viral clearance was carried out within 5–30 days after the most recent test. During the study period 456 patients were diagnosed with RV infection, 265 by PCR and 191 by culture. The median range for duration of shedding (days) by culture and PCR, respectively, were as follows—influenza virus: 13 days (5–38 days) versus 14 days (5–58 days), p 0.5; RSV: 11 days (5–35 days) versus 16 days (5–50 days), p 0.001; PIV: 9 days (5–41 days) versus 17 days (5–45 days), p ≤0.0001; HMPV 10.5 days (5–29 days) versus 14 days (5–42 days), p 0.2. In multivariable analysis, age and underlying disease or transplant were not independently associated with extended shedding regardless of testing method. In high-risk oncology settings for respiratory illness due to RSV and PIV, the virus is detectable by PCR for a longer period of time than by culture and extended shedding is observed.",,"['Richardson, L.', 'Brite, J.', 'Del Castillo, M.', 'Childers, T.', 'Sheahan, A.', 'Huang, Y-T.', 'Dougherty, E.', 'Babady, NE.', 'Sepkowitz, K.', 'Kamboj, M.']",,,,
,PMC,"The role of influenza, RSV and other common respiratory viruses in severe acute respiratory infections and influenza-like illness in a population with a high HIV sero-prevalence, South Africa 2012–2015",http://dx.doi.org/10.1016/j.jcv.2015.12.004,PMC5712432,,,"BACKGROUND: Viruses detected in patients with acute respiratory infections may be the cause of illness or asymptomatic shedding. OBJECTIVE: To estimate the attributable fraction (AF) and the detection rate attributable to illness for each of the different respiratory viruses STUDY DESIGN: We compared the prevalence of 10 common respiratory viruses (influenza A and B viruses, parainfluenza virus 1–3; respiratory syncytial virus (RSV); adenovirus, rhinovirus, human metapneumovirus (hMPV) and enterovirus) in both HIV positive and negative patients hospitalized with severe acute respiratory illness (SARI), outpatients with influenza-like illness (ILI), and control subjects who did not report any febrile, respiratory or gastrointestinal illness during 2012–2015 in South Africa. RESULTS: We enrolled 1959 SARI, 3784 ILI and 1793 controls with a HIV sero-prevalence of 26%, 30% and 43%, respectively. Influenza virus (AF: 86.3%; 95%CI: 77.7–91.6%), hMPV (AF: 85.6%; 95%CI: 72.0–92.6%), and RSV (AF: 83.7%; 95%CI: 77.5–88.2%) infections were associated with severe disease., while rhinovirus (AF: 46.9%; 95%CI: 37.6–56.5%) and adenovirus (AF: 36.4%; 95%CI: 20.6–49.0%) were only moderately associated. CONCLUSIONS: Influenza, RSV and hMPV can be considered pathogens if detected in ILI and SARI while rhinovirus and adenovirus were commonly identified in controls suggesting that they may cause only a proportion of clinical disease observed in positive patients. Nonetheless, they may be important contributors to disease.",,"['Pretorius, Marthi A.', 'Tempia, Stefano', 'Walaza, Sibongile', 'Cohen, Adam L.', 'Moyes, Jocelyn', 'Variava, Ebrahim', 'Dawood, Halima', 'Seleka, Mpho', 'Hellferscee, Orienka', 'Treurnicht, Florette', 'Cohen, Cheryl', 'Venter, Marietjie']",,,,
,PMC,Regulatory oversight of human pathogens and toxins in Canada,http://dx.doi.org/10.14745/ccdr.v41is6a03,PMC5868715,,,"From 1994 to 2009, federal oversight of human pathogens and toxins was limited to facilities importing human pathogens and toxins into Canada under the Human Pathogens Importation Regulations (HPIR). This narrow focus of authority restricted the Government of Canada’s ability to regulate and monitor a full range of activities, including those involving human pathogens and toxins acquired from domestic sources. In 2009, the Human Pathogens and Toxins Act (the Act) received Royal Assent to establish a national safety and security regime and expand oversight through a national, standardized process to verify safe and secure use of human pathogens and toxins in Canada. The Act and the Human Pathogens and Toxins Regulations (the Regulations), in full force since December 1, 2015, provides legislative and statutory requirements for the comprehensive oversight of the control of human pathogens and toxins in Canada. Expanded regulation and monitoring program activities aim to reduce the risks posed by human pathogens and toxins and strengthen biosafety management systems that serve to protect the health of Canadians.",,"['Labrie, C', 'Lecordier, S']",,,,
,PMC,Federal public health strategies to minimize the importation of communicable diseases into Canada,http://dx.doi.org/10.14745/ccdr.v41is6a01,PMC5868714,,,"BACKGROUND: The global spread of communicable diseases is a growing concern largely as a result of increased international travel. In Canada, although most public health management of communicable diseases occurs at the front line, the federal government also takes actions to prevent and mitigate their importation. OBJECTIVE: To describe the role of the Public Health Agency of Canada (PHAC) in minimizing the importation of communicable diseases through preventive measures taken before travellers leave Canada and through early detection and prompt containment measures taken when travellers arrive in the country with a potential communicable disease. INTERVENTIONS: PHAC works to minimize the importation of communicable diseases into Canada by developing evidence-based travel health advice and targeted outreach activities geared to the public and to health care professionals. On the basis of the Quarantine Act and the International Health Regulations (2005), PHAC also conducts inspections of conveyances such as aircraft and boats and works with partners to conduct border screening to assess ill travellers entering the country. CONCLUSION: PHAC plays an important role in preventing and minimizing the importation of communicable diseases into Canada in conjunction with clinicians, public health authorities at all levels of government and other federal government departments.",,"['Bhatia, N', 'Sarwal, S', 'Robinson, H', 'Geduld, J', 'Huneault, F', 'Schreiner, H', 'Collins, S', 'Hickey, R']",,,,
,PMC,Modulation of Mitochondrial Antiviral Signaling by Human Herpesvirus 8 Interferon Regulatory Factor 1,http://dx.doi.org/10.1128/JVI.01903-15,PMC4702585,,,"Mitochondrial lipid raft-like microdomains, experimentally also termed mitochondrial detergent-resistant membrane fractions (mDRM), play a role as platforms for recruiting signaling molecules involved in antiviral responses such as apoptosis and innate immunity. Viruses can modulate mitochondrial functions for their own survival and replication. However, viral regulation of the antiviral responses via mDRM remains incompletely understood. Here, we report that human herpesvirus 8 (HHV-8) gene product viral interferon regulatory factor 1 (vIRF-1) is targeted to mDRM during virus replication and negatively regulates the mitochondrial antiviral signaling protein (MAVS)-mediated antiviral responses. The N-terminal region of vIRF-1 interacts directly with membrane lipids, including cardiolipin. In addition, a GxRP motif within the N terminus of vIRF-1, conserved in the mDRM-targeting region of mitochondrial proteins, including PTEN-induced putative kinase 1 (PINK1) and MAVS, was found to be important for vIRF-1 association with mitochondria. Furthermore, MAVS, which has the potential to promote vIRF-1 targeting to mDRM possibly by inducing cardiolipin exposure on the outer membrane of mitochondria, interacts with vIRF-1, which, in turn, inhibits MAVS-mediated antiviral signaling. Consistent with these results, vIRF-1 targeting to mDRM contributes to promotion of HHV-8 productive replication and inhibition of associated apoptosis. Combined, our results suggest novel molecular mechanisms for negative-feedback regulation of MAVS by vIRF-1 during virus replication. IMPORTANCE Successful virus replication is in large part achieved by the ability of viruses to counteract apoptosis and innate immune responses elicited by infection of host cells. Recently, mitochondria have emerged to play a central role in antiviral signaling. In particular, mitochondrial lipid raft-like microdomains appear to function as platforms in cell apoptosis signaling. However, viral regulation of antiviral signaling through the mitochondrial microdomains remains incompletely understood. The present study demonstrates that HHV-8-encoded vIRF-1 targets to the mitochondrial detergent-resistant microdomains via direct interaction with cardiolipin and inhibits MAVS protein-mediated apoptosis and type I interferon gene expression in a negative-feedback manner, thus promoting HHV-8 productive replication. These results suggest that vIRF-1 is the first example of a viral protein to inhibit mitochondrial antiviral signaling through lipid raft-like microdomains.",,"['Hwang, Keun Young', 'Choi, Young Bong']",,,,
,PMC,Characterization and Demonstration of the Value of a Lethal Mouse Model of Middle East Respiratory Syndrome Coronavirus Infection and Disease,http://dx.doi.org/10.1128/JVI.02009-15,PMC4702581,,,"Characterized animal models are needed for studying the pathogenesis of and evaluating medical countermeasures for persisting Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. Here, we further characterized a lethal transgenic mouse model of MERS-CoV infection and disease that globally expresses human CD26 (hCD26)/DPP4. The 50% infectious dose (ID(50)) and lethal dose (LD(50)) of virus were estimated to be <1 and 10 TCID(50) of MERS-CoV, respectively. Neutralizing antibody developed in the surviving mice from the ID(50)/LD(50) determinations, and all were fully immune to challenge with 100 LD(50) of MERS-CoV. The tissue distribution and histopathology in mice challenged with a potential working dose of 10 LD(50) of MERS-CoV were subsequently evaluated. In contrast to the overwhelming infection seen in the mice challenged with 10(5) LD(50) of MERS-CoV, we were able to recover infectious virus from these mice only infrequently, although quantitative reverse transcription-PCR (qRT-PCR) tests indicated early and persistent lung infection and delayed occurrence of brain infection. Persistent inflammatory infiltrates were seen in the lungs and brain stems at day 2 and day 6 after infection, respectively. While focal infiltrates were also noted in the liver, definite pathology was not seen in other tissues. Finally, using a receptor binding domain protein vaccine and a MERS-CoV fusion inhibitor, we demonstrated the value of this model for evaluating vaccines and antivirals against MERS. As outcomes of MERS-CoV infection in patients differ greatly, ranging from asymptomatic to overwhelming disease and death, having available both an infection model and a lethal model makes this transgenic mouse model relevant for advancing MERS research. IMPORTANCE Fully characterized animal models are essential for studying pathogenesis and for preclinical screening of vaccines and drugs against MERS-CoV infection and disease. When given a high dose of MERS-CoV, our transgenic mice expressing hCD26/DPP4 viral receptor uniformly succumbed to death within 6 days, making it difficult to evaluate host responses to infection and disease. We further characterized this model by determining both the ID(50) and the LD(50) of MERS-CoV in order to establish both an infection model and a lethal model for MERS and followed this by investigating the antibody responses and immunity of the mice that survived MERS-CoV infection. Using the estimated LD(50) and ID(50) data, we dissected the kinetics of viral tissue distribution and pathology in mice challenged with 10 LD(50) of virus and utilized the model for preclinical evaluation of a vaccine and drug for treatment of MERS-CoV infection. This further-characterized transgenic mouse model will be useful for advancing MERS research.",,"['Tao, Xinrong', 'Garron, Tania', 'Agrawal, Anurodh Shankar', 'Algaissi, Abdullah', 'Peng, Bi-Hung', 'Wakamiya, Maki', 'Chan, Teh-Sheng', 'Lu, Lu', 'Du, Lanying', 'Jiang, Shibo', 'Couch, Robert B.', 'Tseng, Chien-Te K.']",,,,
,PMC,Ebolavirus Glycoprotein Directs Fusion through NPC1(+) Endolysosomes,http://dx.doi.org/10.1128/JVI.01828-15,PMC4702577,,,"Ebolavirus, a deadly hemorrhagic fever virus, was thought to enter cells through endolysosomes harboring its glycoprotein receptor, Niemann-Pick C1. However, an alternate model was recently proposed in which ebolavirus enters through a later NPC1-negative endosome that contains two-pore Ca(2+) channel 2 (TPC2), a newly identified ebolavirus entry factor. Here, using live cell imaging, we obtained evidence that in contrast to the new model, ebolavirus enters cells through endolysosomes that contain both NPC1 and TPC2.",,"['Simmons, James A.', ""D'Souza, Ryan S."", 'Ruas, Margarida', 'Galione, Antony', 'Casanova, James E.', 'White, Judith M.']",,,,
,PMC,Duck Interferon-Inducible Transmembrane Protein 3 Mediates Restriction of Influenza Viruses,http://dx.doi.org/10.1128/JVI.01593-15,PMC4702568,,,"Interferon-inducible transmembrane proteins (IFITMs) can restrict the entry of a wide range of viruses. IFITM3 localizes to endosomes and can potently restrict the replication of influenza A viruses (IAV) and several other viruses that also enter host cells through the endocytic pathway. Here, we investigate whether IFITMs are involved in protection in ducks, the natural host of influenza virus. We identify and sequence duck IFITM1, IFITM2, IFITM3, and IFITM5. Using quantitative PCR (qPCR), we demonstrate the upregulation of these genes in lung tissue in response to highly pathogenic IAV infection by 400-fold, 30-fold, 30-fold, and 5-fold, respectively. We express each IFITM in chicken DF-1 cells and show duck IFITM1 localizes to the cell surface, while IFITM3 localizes to LAMP1-containing compartments. DF-1 cells stably expressing duck IFITM3 (but not IFITM1 or IFITM2) show increased restriction of replication of H1N1, H6N2, and H11N9 IAV strains but not vesicular stomatitis virus. Although duck and human IFITM3 share only 38% identity, critical residues for viral restriction are conserved. We generate chimeric and mutant IFITM3 proteins and show duck IFITM3 does not require its N-terminal domain for endosomal localization or antiviral function; however, this N-terminal end confers endosomal localization and antiviral function on IFITM1. In contrast to mammalian IFITM3, the conserved YXXθ endocytosis signal sequence in the N-terminal domain of duck IFITM3 is not essential for correct endosomal localization. Despite significant structural and amino acid divergence, presumably due to host-virus coevolution, duck IFITM3 is functional against IAV. IMPORTANCE Immune IFITM genes are poorly conserved across species, suggesting that selective pressure from host-specific viruses has driven this divergence. We wondered whether coevolution between viruses and their natural host would result in the evasion of IFITM restriction. Ducks are the natural host of avian influenza A viruses and display few or no disease symptoms upon infection with most strains, including highly pathogenic avian influenza. We have characterized the duck IFITM locus and identified IFITM3 as an important restrictor of several influenza A viruses, including avian strains. With only 38% amino acid identity to human IFITM3, duck IFITM3 possesses antiviral function against influenza virus. Thus, despite long coevolution of virus and host effectors in the natural host, influenza virus evasion of IFITM3 restriction in ducks is not apparent.",,"['Blyth, Graham A. D.', 'Chan, Wing Fuk', 'Webster, Robert G.', 'Magor, Katharine E.']",,,,
,PMC,Hepatitis C Virus NS4B Can Suppress STING Accumulation To Evade Innate Immune Responses,http://dx.doi.org/10.1128/JVI.01720-15,PMC4702547,,,"The cyclic dinucleotide 2′,3′-cGAMP can bind the adaptor protein STING (stimulator of interferon [IFN] genes) to activate the production of type I IFNs and proinflammatory cytokines. We found that cGAMP added to the culture medium could suppress the replication of the hepatitis C virus (HCV) genotype 1b strain Con1 subgenomic replicon in human hepatoma cells. Knockdown of STING expression diminished the inhibitory effect on replicon replication, while overexpression of STING enhanced the inhibitory effects of cGAMP. The addition of cGAMP into 1b/Con1 replicon cells significantly increased the expression of type I IFNs and antiviral interferon-stimulated genes. Unexpectedly, replication of the genotype 2a JFH1 replicon and infectious JFH1 virus was less sensitive to the inhibitory effect of cGAMP than was that of 1b/Con1 replicon. Using chimeric replicons, 2a NS4B was identified to confer resistance to cGAMP. Transient expression of 2a NS4B resulted in a pronounced inhibitory effect on STING-mediated beta IFN (IFN-β) reporter activation compared to that of 1b NS4B. 2a NS4B was found to suppress STING accumulation in a dose-dependent manner. The predicted transmembrane domain of 2a NS4B was required to inhibit STING accumulation. These results demonstrate a novel genotype-specific inhibition of the STING-mediated host antiviral immune response. IMPORTANCE The cyclic dinucleotide cGAMP was found to potently inhibit the replication of HCV genotype 1b Con1 replicon but was less effective for the 2a/JFH1 replicon and infectious JFH1 virus. The predicted transmembrane domain in 2a NS4B was shown to be responsible for the decreased sensitivity to cGAMP. The N terminus of NS4B has been reported to suppress STING-mediated signaling by disrupting the interaction of STING and TBK1 and/or MAVS. We show that 2a/JFH1 NS4B has an additional mechanism to evade STING signaling through suppressing STING accumulation.",,"['Yi, Guanghui', 'Wen, Yahong', 'Shu, Chang', 'Han, Qingxia', 'Konan, Kouacou V.', 'Li, Pingwei', 'Kao, C. Cheng']",,,,
,PMC,Critical Role of K1685 and K1829 in the Large Protein of Rabies Virus in Viral Pathogenicity and Immune Evasion,http://dx.doi.org/10.1128/JVI.02050-15,PMC4702542,,,"Rabies, one of the oldest infectious diseases, still presents a public health threat in most parts of the world today. Its pathogen, rabies virus (RABV), can utilize its viral proteins, such as the nucleoprotein and phosphorylation protein, to subvert the host innate immune system. For a long time, the large (L) protein was believed to be essential for RABV transcription and replication, but its role in viral pathogenicity and immune evasion was not known. Recent studies have found that the conserved K-D-K-E tetrad motif in the L protein is related to the methyltransferase (MTase) activity in the viral mRNA process. In the present study, a series of RABV mutations in this motif was constructed with the recombinant CVS-B2c (rB2c) virus. Two of these mutants, rB2c-K1685A and rB2c-K1829A, were found to be stable and displayed an attenuated phenotype in both in vitro growth and in vivo pathogenicity in adult and suckling mice. Further studies demonstrated that these two mutants were more sensitive to the expression of the interferon-stimulated gene product IFIT2 than the parent virus. Taken together, our results suggest that K1685 and K1829 in the L protein play important roles in pathogenicity and immune evasion during RABV infection. IMPORTANCE Rabies continues to present a public health threat in most areas of the world, especially in the developing countries of Asia and Africa. The pathogenic mechanisms for rabies are not well understood. In the present study, it was found that the recombinant rabies viruses rB2c-K1685A and rB2c-K1829A, carrying mutations at the predicted MTase catalytic sites in the L protein, were highly attenuated both in vitro and in vivo. Further studies showed that these mutants were more sensitive to the expression of the interferon-stimulated gene product IFIT2 than the parent virus. These findings improve our understanding of rabies pathogenesis, which may help in developing potential therapeutics and an avirulent rabies vaccine.",,"['Tian, Dayong', 'Luo, Zhaochen', 'Zhou, Ming', 'Li, Mingming', 'Yu, Lan', 'Wang, Chong', 'Yuan, Jiaolong', 'Li, Fang', 'Tian, Bin', 'Sui, Baokun', 'Chen, Huanchun', 'Fu, Zhen F.', 'Zhao, Ling']",,,,
,PMC,"The population genetics of drug resistance evolution in natural populations of viral, bacterial and eukaryotic pathogens",http://dx.doi.org/10.1111/mec.13474,PMC4943078,,,"Drug resistance is a costly consequence of pathogen evolution and a major concern in public health. In this review, we show how population genetics can be used to study the evolution of drug resistance and also how drug resistance evolution is informative as an evolutionary model system. We highlight five examples from diverse organisms with particular focus on: (i) identifying drug resistance loci in the malaria parasite Plasmodium falciparum using the genomic signatures of selective sweeps, (ii) determining the role of epistasis in drug resistance evolution in influenza, (iii) quantifying the role of standing genetic variation in the evolution of drug resistance in HIV, (iv) using drug resistance mutations to study clonal interference dynamics in tuberculosis and (v) analysing the population structure of the core and accessory genome of Staphylococcus aureus to understand the spread of methicillin resistance. Throughout this review, we discuss the uses of sequence data and population genetic theory in studying the evolution of drug resistance.",,"['WILSON, BENJAMIN A.', 'GARUD, NANDITA R.', 'FEDER, ALISON F.', 'ASSAF, ZOE J.', 'PENNINGS, PLEUNI S.']",,,,
,PMC,"Integrated, multi-cohort analysis identifies conserved transcriptional signatures across multiple respiratory viruses",http://dx.doi.org/10.1016/j.immuni.2015.11.003,PMC4684904,,,"Respiratory viral infections are a significant burden to healthcare worldwide. Many whole genome expression profiles have identified different respiratory viral infection signatures, but these have not translated to clinical practice. Here, we performed two integrated, multi-cohort analyses of publicly available transcriptional data of viral infections. First, we identified a common host signature across different respiratory viral infections that could distinguish (a) individuals with viral infections from healthy controls and from those with bacterial infections, and (b) symptomatic from asymptomatic subjects prior to symptom onset in challenge studies. Second, we identified an influenza-specific host response signature that (a) could distinguish influenza-infected samples from those with bacterial and other respiratory viral infections, (b) was a diagnostic and prognostic marker in influenza-pneumonia patients and influenza challenge studies, and (c) was predictive of response to influenza vaccine. Our results have applications in the diagnosis, prognosis, and identification of drug targets in viral infections.",,"['Andres-Terre, Marta', 'McGuire, Helen M', 'Pouliot, Yannick', 'Bongen, Erika', 'Sweeney, Timothy E.', 'Tato, Cristina M', 'Khatri, Purvesh']",,,,
,PMC,Autophagy postpones apoptotic cell death in PRRSV infection through Bad-Beclin1 interaction,http://dx.doi.org/10.1080/21505594.2015.1131381,PMC4994821,,,"Autophagy and apoptosis play significant roles in PRRSV infection and replication. However, the interaction between these 2 processes in PRRSV replication is still far from been completely understood. In our studies, the exposure of MARC-145 cells to PRRSV confirmed the activation of autophagy and subsequent induction of apoptosis. The inhibition of autophagy by 3-methyladenine (3-MA) caused a significant increase in PRRSV-induced apoptosis, showing a potential connection between both mechanisms. Moreover, we observed an increase in Bad expression (a pro-apoptotic protein) and Beclin1 (an autophagy regulator) in virus-infected cells up to 36h. Co-immunoprecipitation assays showed the formation of Bad and Beclin1 complex in PRRSV infected cells. Accordingly, Bad co-localized with Beclin1 in MARC-145 infected cells. Knockdown of Beclin1 significantly decreased PRRSV replication and PRRSV-induced autophagy, while Bad silencing resulted in increased autophagy and enhanced viral replication. Furthermore, PRRSV infection phosphorylated Bad (Ser112) to promote cellular survival. These results demonstrate that autophagy can favor PRRSV replication by postponing apoptosis through the formation of a Bad-Beclin1 complex.",,"['Zhou, Ao', 'Li, Shuaifeng', 'Khan, Faheem Ahmed', 'Zhang, Shujun']",,,,
,PMC,Increased morbidity and mortality in domestic animals eating dropped and bitten fruit in Bangladeshi villages: Implications for zoonotic disease transmission,http://dx.doi.org/10.1007/s10393-015-1080-x,PMC4940180,,,"We used data on feeding practices and domestic animal health gathered from 207 Bangladeshi villages to identify any association between grazing dropped fruit found on the ground or owners directly feeding bat or bird-bitten fruit and animal health. We compared mortality and morbidity in domestic animals using a mixed effects model controlling for village clustering, herd size, and proxy measures of household wealth. Thirty percent of household heads reported that their animals grazed on dropped fruit and 20% reported that they actively fed bitten fruit to their domestic herds. Household heads allowing their cattle to graze on dropped fruit were more likely to report an illness within their herd (adjusted prevalence ratio 1.17, 95% CI 1.02-1.31). Household heads directly feeding goats bitten fruit were more likely to report illness (adjusted prevalence ratio 1.35, 95% CI 1.16-1.57) and deaths (adjusted prevalence ratio 1.64, 95% CI 1.13-2.4). Reporting of illnesses and deaths among goats rose as the frequency of feeding bitten fruit increased. One possible explanation for this finding is the transmission of bat pathogens to domestic animals via bitten fruit consumption.",,"['Openshaw, John J.', 'Hegde, Sonia', 'Sazzad, Hossain M. S.', 'Khan, Salah Uddin', 'Hossain, M. Jahangir', 'Epstein, Jonathan H.', 'Daszak, Peter', 'Gurley, Emily S.', 'Luby, Stephen P.']",,,,
,PMC,Human RNase L tunes gene expression by selectively destabilizing the microRNA-regulated transcriptome,http://dx.doi.org/10.1073/pnas.1513034112,PMC4702973,,,Double-stranded RNA (dsRNA) activates the innate immune system of mammalian cells and triggers intracellular RNA decay by the pseudokinase and endoribonuclease RNase L. RNase L protects from pathogens and regulates cell growth and differentiation by destabilizing largely unknown mammalian RNA targets. We developed an approach for transcriptome-wide profiling of RNase L activity in human cells and identified hundreds of direct RNA targets and nontargets. We show that this RNase L-dependent decay selectively affects transcripts regulated by microRNA (miR)-17/miR-29/miR-200 and other miRs that function as suppressors of mammalian cell adhesion and proliferation. RNase L mimics the effects of these miRs and acts as a suppressor of proliferation and adhesion in mammalian cells. Our data suggest that RNase L-dependent decay serves to establish an antiproliferative state via destabilization of the miR-regulated transcriptome.,,"['Rath, Sneha', 'Donovan, Jesse', 'Whitney, Gena', 'Chitrakar, Alisha', 'Wang, Wei', 'Korennykh, Alexei']",,,,
,PMC,Reprogramming the genetic code: the emerging role of ribosomal frameshifting in regulating cellular gene expression,http://dx.doi.org/10.1002/bies.201500131,PMC4749135,,,"Reading frame maintenance is a critical property of ribosomes. However, a number of genetic elements have been described that can induce ribosomes to shift on mRNAs, the most well understood of which are a class that directs ribosomal slippage by one base in 5′ (-1) direction. This is referred to as programmed -1 ribosomal frameshifting (-1 PRF). Recently, a new -1 PRF promoting element was serendipitously discovered in a study examining the effects of stretches of adenosines in the coding sequences of mRNAs. Here, we discuss this finding, recent studies describing how -1 PRF is used to control gene expression in eukaryotes, and how -1 PRF is itself regulated. The implications of dysregulation of -1 PRF on human health are examined, as are possible new areas in which novel -1 PRF promoting elements might be discovered.",,"['Advani, Vivek M.', 'Dinman, Jonathan D.']",,,,
,PMC,Bioterrorism and the Role of the Clinical Microbiology Laboratory,http://dx.doi.org/10.1128/CMR.00033-15,PMC4771219,,,"Regular review of the management of bioterrorism is essential for maintaining readiness for these sporadically occurring events. This review provides an overview of the history of biological disasters and bioterrorism. I also discuss the recent recategorization of tier 1 agents by the U.S. Department of Health and Human Services, the Laboratory Response Network (LRN), and specific training and readiness processes and programs, such as the College of American Pathologists (CAP) Laboratory Preparedness Exercise (LPX). LPX examined the management of cultivable bacterial vaccine and attenuated strains of tier 1 agents or close mimics. In the LPX program, participating laboratories showed improvement in the level of diagnosis required and referral of isolates to an appropriate reference laboratory. Agents which proved difficult to manage in sentinel laboratories included the more fastidious Gram-negative organisms, especially Francisella tularensis and Burkholderia spp. The recent Ebola hemorrhagic fever epidemic provided a check on LRN safety processes. Specific guidelines and recommendations for laboratory safety and risk assessment in the clinical microbiology are explored so that sentinel laboratories can better prepare for the next biological disaster.",,"Wagar, Elizabeth",,,,
,PMC,Sendai Virus as a Backbone for Vaccines against RSV and other Human Paramyxoviruses,http://dx.doi.org/10.1586/14760584.2016.1114418,PMC4957581,,,"Human paramyxoviruses are the etiological agents for life-threatening respiratory virus infections of infants and young children. These viruses – including respiratory syncytial virus (RSV), the human parainfluenza viruses (hPIV1-4), and human metapneumovirus (hMPV) – are responsible for millions of serious lower respiratory tract infections each year worldwide. There are currently no standard treatments and no licensed vaccines for any of these pathogens. Here we review research with which Sendai virus, a mouse parainfluenza virus type 1, is being advanced as a Jennerian vaccine for hPIV1 and as a backbone for RSV, hMPV, and other hPIV vaccines for children.",,"['Russell, Charles J.', 'Hurwitz, Julia L.']",,,,
,PMC,The Refugee Crisis in the Middle East and Public Health,http://dx.doi.org/10.2105/AJPH.2015.302929,PMC4638237,,,,,"['Morabia, Alfredo', 'Benjamin, Georges C.']",,,,
,PMC,"The Woodchuck, a Nonprimate Model for Immunopathogenesis and Therapeutic Immunomodulation in Chronic Hepatitis B Virus Infection",http://dx.doi.org/10.1101/cshperspect.a021451,PMC4665037,,,"The woodchuck hepatitis virus (WHV) and its host, the eastern woodchuck, is a very valuable model system for hepatitis B virus infection. Many aspects of WHV replication and pathogenesis resemble acute and chronic hepatitis B infection in patients. Since the establishment of immunological tools, woodchucks were used to develop new therapeutic vaccines and immunomodulatory approaches to treat chronic hepadnaviral infections. Combination therapy of nucleos(t)ide analogs, with prime–boost vaccination and triple therapy, including immunomodulatory strategies by blocking the interaction of the programmed death-1 (PD-1) receptor with its ligand inducing a potent T-cell response in chronic WHV carrier woodchucks, suppression of viral replication, and complete elimination of the virus in 30% of the animals. Both strategies may be used for future therapies in patients with chronic hepatitis B.",,"['Roggendorf, Michael', 'Kosinska, Anna D.', 'Liu, Jia', 'Lu, Mengji']",,,,
,PMC,Systemic Coronaviral Disease in 5 Ferrets,,PMC4681245,,,"The prevalence of reported systemic coronaviral disease in ferrets (Mustela putorius furo), which resembles the dry form of feline infectious peritonitis, has been increasing in the literature since its initial diagnosis and characterization approximately 10 y ago. Here we describe the clinical signs, pathologic findings, and diagnosis by immunohistochemistry using an FIPV3-70 monoclonal antibody of systemic coronaviral disease in 5 ferrets, 2 of which were strictly laboratory-housed; the remaining 3 were referred from veterinary private practices. This case report illustrates the importance of considering FRSCV infection as a differential diagnosis in young, debilitated ferrets with abdominal masses and other supporting clinical signs.",,"['Autieri, Christopher R', 'Miller, Cassandra L', 'Scott, Kathleen E', 'Kilgore, Alexandra', 'Papscoe, Victoria A', 'Garner, Michael M', 'Haupt, Jennifer L', 'Bakthavatchalu, Vasudevan', 'Muthupalani, Sureshkumar', 'Fox, James G']",,,,
,PMC,Struvite Urolithiasis in Long–Evans Rats,,PMC4681242,,,"Struvite urinary calculi, which are composed of magnesium, ammonium, and phosphate, can cause complications including sepsis and renal failure. Struvite calculi were identified within the urinary bladder and renal pelvis of 2 Long-Evans rats that died within days after arrival from a commercial vendor. The remaining rats in the shipment were screened by physical examination, radiography, and ultrasonography, revealing an additional 2 animals that were clinically affected. These rats were euthanized, necropsied, and yielded similar findings to those from the first 2 rats. In addition, urine samples had an alkaline pH and contained numerous bacteria (predominantly Proteus mirabilis), leukocytes, and crystals. All calculi were composed completely of struvite. Another 7 rats in the shipment had alkaline urine with the presence of blood cells; 6 of these rats also had abundant struvite crystals, and P. mirabilis was cultured from the urine of 3 rats. Further investigation by the vendor identified 2 of 100 rats with struvite calculi from the same colony. Although no specific cause could be implicated, the fact that all the affected rats came from the same breeding area suggests a genetic or environmental triggering event; a contribution due to diet cannot be ruled out. Our findings suggest that the affected rats had metabolic disturbances coupled with bacterial infection that predisposed them to develop struvite calculi. During sudden increases of struvite urinary calculi cases in rats, urine cultures followed by appropriate surgical intervention and antibiotic therapy is warranted. Additional factors, including diet, merit attention as well.",,"['Pang, Jassia', 'Borjeson, Tiffany M', 'Parry, Nicola MA', 'Fox, James G']",,,,
,PMC,"The ABCs of the US Broad Spectrum Antimicrobials Program: Antibiotics, Biosecurity, and Congress",http://dx.doi.org/10.1089/hs.2015.0034,PMC4685490,,,"Antibiotic resistance has been increasing at an alarming rate in the United States and globally for decades, but the problem has only recently gained broad attention at the highest levels of the US government. More and more patients are dying of infections that do not respond to antibiotics that are currently available. Meanwhile, the antibacterial product pipeline remains fragile in part because of a lack of commercial interest from pharmaceutical companies. The Biomedical Advanced Research and Development Authority (BARDA) Broad Spectrum Antimicrobials (BSA) program leads the US government's effort to bridge this gap by advancing new antibacterials through late stages of clinical development. Other commentators have described in detail BARDA's structure, process, and role in antibacterial development. This commentary offers a public policy perspective on the emerging politics of antibiotic resistance in the context of US biosecurity politics and medical countermeasure (MCM) development. It identifies promising developments and difficult challenges that together will ultimately determine whether BARDA can become a global leader for antibiotic development.",,"Billington, John K.",,,,
,PMC,ACE2 and Microbiota: Emerging Targets for Cardiopulmonary Disease Therapy,http://dx.doi.org/10.1097/FJC.0000000000000307,PMC4807023,,,"The health of the cardiovascular and pulmonary systems is inextricably linked to the renin-angiotensin system (RAS). Physiologically speaking, a balance between the vasodeleterious (ACE/Ang II/AT(1)R) and vasoprotective (ACE2/Ang-(1–7)/MasR) components of the RAS is critical for cardiopulmonary homeostasis. Upregulation of the ACE/Ang II/AT(1)R axis shifts the system toward vasoconstriction, proliferation, hypertrophy, inflammation, and fibrosis, all factors that contribute to the development and progression of cardiopulmonary diseases. Conversely, stimulation of the vasoprotective ACE2/Ang-(1–7)/MasR axis produces a counter-regulatory response that promotes cardiovascular health. Current research is investigating novel strategies to augment actions of the vasoprotective RAS components, particularly ACE2, in order to treat various pathologies. While multiple approaches to increase the activity of ACE2 have displayed beneficial effects against experimental disease models, the mechanisms behind its protective actions remain incompletely understood. Recent work demonstrating a non-catalytic role for ACE2 in amino acid transport in the gut has led us to speculate that the therapeutic effects of ACE2 can be mediated, in part, by its actions on the gastrointestinal tract and/or gut microbiome. This is consistent with emerging data which suggests that dysbiosis of the gut and lung microbiomes is associated with cardiopulmonary disease. This review highlights new developments in the protective actions of ACE2 against cardiopulmonary disorders, discusses innovative approaches to targeting ACE2 for therapy, and explores an evolving role for gut and lung microbiota in cardiopulmonary health.",,"['Cole-Jeffrey, Colleen T', 'Liu, Meng', 'Katovich, Michael J', 'Raizada, Mohan K', 'Shenoy, Vinayak']",,,,
,PMC,The proteome of the infectious bronchitis virus Beau-R virion,http://dx.doi.org/10.1099/jgv.0.000304,PMC5410111,,,"Infectious bronchitis is a highly contagious respiratory disease of poultry caused by the coronavirus infectious bronchitis virus (IBV). It was thought that coronavirus virions were composed of three major viral structural proteins until investigations of other coronaviruses showed that the virions also include viral non-structural and genus-specific accessory proteins as well as host-cell proteins. To study the proteome of IBV virions, virus was grown in embryonated chicken eggs, purified by sucrose-gradient ultracentrifugation and analysed by mass spectrometry. Analysis of three preparations of purified IBV yielded the three expected structural proteins plus 35 additional virion-associated host proteins. The virion-associated host proteins had a diverse range of functional attributions, being involved in cytoskeleton formation, RNA binding and protein folding pathways. Some of these proteins were unique to this study, while others were found to be orthologous to proteins identified in severe acute respiratory syndrome coronavirus virions and also virions from a number of other RNA and DNA viruses.",,"['Dent, Stuart D.', 'Xia, Dong', 'Wastling, Jonathan M.', 'Neuman, Benjamin W.', 'Britton, Paul', 'Maier, Helena J.']",,,,
,PMC,Chloroquine inhibited Ebola virus replication in vitro but failed to protect against infection and disease in the in vivo guinea pig model,http://dx.doi.org/10.1099/jgv.0.000309,PMC5410110,,,"Ebola virus (EBOV) is highly pathogenic, with a predisposition to cause outbreaks in human populations accompanied by significant mortality. Owing to the lack of approved therapies, screening programmes of potentially efficacious drugs have been undertaken. One of these studies has demonstrated the possible utility of chloroquine against EBOV using pseudotyped assays. In mouse models of EBOV disease there are conflicting reports of the therapeutic effects of chloroquine. There are currently no reports of its efficacy using the larger and more stringent guinea pig model of infection. In this study we have shown that replication of live EBOV is impaired by chloroquine in vitro. However, no protective effects were observed in vivo when EBOV-infected guinea pigs were treated with chloroquine. These results advocate that chloroquine should not be considered as a treatment strategy for EBOV.",,"['Dowall, Stuart D.', 'Bosworth, Andrew', 'Watson, Robert', 'Bewley, Kevin', 'Taylor, Irene', 'Rayner, Emma', 'Hunter, Laura', 'Pearson, Geoff', 'Easterbrook, Linda', 'Pitman, James', 'Hewson, Roger', 'Carroll, Miles W.']",,,,
,PMC,KOREAN MEDICAL ASSOCIATION(),,PMC4829780,,,,,"KANG, Cheong Hee",,,,
,PMC,"STING: infection, inflammation and cancer",http://dx.doi.org/10.1038/nri3921,PMC5004891,,,"The rapid detection of microbial agents is essential for the effective initiation of host defence mechanisms against infection. Understanding how cells detect cytosolic DNA to trigger innate immune gene transcription has important implications — not only for comprehending the immune response to pathogens but also for elucidating the causes of autoinflammatory disease involving the sensing of self-DNA and the generation of effective antitumour adaptive immunity. The discovery of the STING (stimulator of interferon genes)-controlled innate immune pathway, which mediates cytosolic DNA-induced signalling events, has recently provided important insights into these processes, opening the way for the development of novel immunization regimes, as well as therapies to treat autoinflammatory disease and cancer.",,"Barber, Glen N.",,,,
,PMC,Vasoregression: A Shared Vascular Pathology Underlying Macrovascular And Microvascular Pathologies?,http://dx.doi.org/10.1089/omi.2015.0128,PMC4684001,,,"Vasoregression is a common phenomenon underlying physiological vessel development as well as pathological microvascular diseases leading to peripheral neuropathy, nephropathy, and vascular oculopathies. In this review, we describe the hallmarks and pathways of vasoregression. We argue here that there is a parallel between characteristic features of vasoregression in the ocular microvessels and atherosclerosis in the larger vessels. Shared molecular pathways and molecular effectors in the two conditions are outlined, thus highlighting the possible systemic causes of local vascular diseases. Our review gives us a system-wide insight into factors leading to multiple synchronous vascular diseases. Because shared molecular pathways might usefully address the diagnostic and therapeutic needs of multiple common complex diseases, the literature analysis presented here is of broad interest to readership in integrative biology, rational drug development and systems medicine.",,"['Gupta, Akanksha', 'Bhatnagar, Sonika']",,,,
,PMC,Middle East respiratory syndrome coronavirus (MERS-CoV): animal to human interaction,http://dx.doi.org/10.1080/20477724.2015.1122852,PMC4809235,,,"The Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel enzootic betacoronavirus that was first described in September 2012. The clinical spectrum of MERS-CoV infection in humans ranges from an asymptomatic or mild respiratory illness to severe pneumonia and multi-organ failure; overall mortality is around 35.7%. Bats harbour several betacoronaviruses that are closely related to MERS-CoV but more research is needed to establish the relationship between bats and MERS-CoV. The seroprevalence of MERS-CoV antibodies is very high in dromedary camels in Eastern Africa and the Arabian Peninsula. MERS-CoV RNA and viable virus have been isolated from dromedary camels, including some with respiratory symptoms. Furthermore, near-identical strains of MERS-CoV have been isolated from epidemiologically linked humans and camels, confirming inter-transmission, most probably from camels to humans. Though inter-human spread within health care settings is responsible for the majority of reported MERS-CoV cases, the virus is incapable at present of causing sustained human-to-human transmission. Clusters can be readily controlled with implementation of appropriate infection control procedures. Phylogenetic and sequencing data strongly suggest that MERS-CoV originated from bat ancestors after undergoing a recombination event in the spike protein, possibly in dromedary camels in Africa, before its exportation to the Arabian Peninsula along the camel trading routes. MERS-CoV serosurveys are needed to investigate possible unrecognized human infections in Africa. Amongst the important measures to control MERS-CoV spread are strict regulation of camel movement, regular herd screening and isolation of infected camels, use of personal protective equipment by camel handlers and enforcing rules banning all consumption of unpasteurized camel milk and urine.",,"['Omrani, Ali S.', 'Al-Tawfiq, Jaffar A.', 'Memish, Ziad A.']",,,,
,PMC,Human Metapneumovirus Infection in Jordanian Children: Epidemiology and Risk Factors for Severe Disease,http://dx.doi.org/10.1097/INF.0000000000000892,PMC4875771,,,"BACKGROUND: Human metapneumovirus (HMPV) is a leading cause of acute respiratory tract infection (ARTI) in young children. Our objectives were to define HMPV epidemiology and circulating strains and determine markers of severe disease in Jordanian children. METHODS: We conducted a prospective study March 16, 2010-March 31, 2013 using quantitative RT-PCR to determine the frequency of HMPV infection among children <2 years old admitted with fever and/or acute respiratory illness to a major government hospital in Amman, Jordan. RESULTS: HMPV was present in 273/3168 (8.6%) of children presenting with ARTI. HMPV A2, B1, and B2, but not A1, were detected during the 3-year period. HMPV-infected children were older and more likely to be diagnosed with bronchopneumonia than HMPV-negative children. HMPV-infected children with lower respiratory tract infection (LRTI) had higher rates of cough and shortness of breath than children with LRTI infected with other or no identifiable viruses. Symptoms and severity were not different between children with HMPV only compared with HMPV co-infection. Children with HMPV subgroup A infection were more likely to require supplemental oxygen. In a multivariate analysis, HMPV subgroup A and age <6 months were independently associated with supplemental oxygen requirement. CONCLUSIONS: HMPV is a leading cause of acute respiratory tract disease in Jordanian children <2 years old. HMPV A and young age were associated with severe disease. Ninety percent of HMPV-infected hospitalized children were full-term and otherwise healthy, in contrast to high-income nations; thus, factors contributing to disease severity likely vary depending on geographic and resource differences.",,"['Schuster, Jennifer E.', 'Khuri-Bulos, Najwa', 'Faouri, Samir', 'Shehabi, Asem', 'Johnson, Monika', 'Wang, Li', 'Fonnesbeck, Christopher', 'Williams, John V.', 'Halasa, Natasha']",,,,
,PMC,Evaluation of epidemiological and clinical features of influenza and other respiratory viruses,http://dx.doi.org/10.5152/TurkPediatriArs.2015.2827,PMC4743864,,,"AIM: In our study, we aimed to clinically and epidemiologically evaluate respiratory tract infections the viral agents of which were detected by molecular methods and to compare influenza and other respiratory tract viruses in this context. MATERIAL AND METHODS: The records of 178 patients aged above 2 years who presented to pediatric emergency outpatient clinic with fever and respiratory tract infection findings between December 2013 and April 2014 were examined retrospectively. RESULTS: At least one respiratory tract pathogen was detected by polymerase chain reaction in 78.6% (n=140) of the patients: influenza A 33.5%, influenza B 16.4%, respiratory syncytial virus 9.2%, adenovirus 7.8%, rhinovirus 7.1%, coronavirus 7.1%, human metapneumovirus 5.7%, human bocavirus 5.7%, parainfluenza virus 3.5%, coinfection 2.8%. The mean age of the patients was 6.3±3.6 years. Sixty-nine patients (49.2%) were aged between 2 and 5 years. Seventy-one patients (50.7%) were aged 5 years and above. Upper respiratory tract infection was found with a rate of 65.7% and lower respiratory tract infection was found with a rate of 34.2%. It was observed that the distribution of respiratory tract viruses showed variance by age groups. Influenza A infection was observed with the highest rate in both age groups. Influenza B was the second leading agent (p=0.008) above the age of 5 years and respiratory syncytial virus was the second leading agent in the 2–5 year age group (p=0.003). Influenza viruses were detected in 55.9% of 118 patients who were found to be compatible with the definition of “influenza-like illness” specified in the Center for Disease Control and Prevention guidelines and other viral agenst were detected in 44%. No difference could be found between the clinical pictures and radiological findings caused by influenza and other respiratory tract viruses. CONCLUSIONS: In this study, it was concluded that influenza and other respiratory viruses can not be differentiated definitely by clinical and radiological findings, though there are some differences.",,"['Aktürk, Hacer', 'Sütçü, Murat', 'Badur, Selim', 'Törün, Selda Hançerli', 'Çıtak, Agop', 'Erol, Oğuz Bülent', 'Somer, Ayper', 'Salman, Nuran']",,,,
,PMC,Potent Inhibition of Enterovirus D68 and Human Rhinoviruses by Dipeptidyl Aldehydes and α-Ketoamides,http://dx.doi.org/10.1016/j.antiviral.2015.11.010,PMC4698184,,,"Enterovirus D68 (EV-D68) is an emerging pathogen responsible for mild to severe respiratory infections that occur mostly in infants, children and teenagers. EV-D68, one of more than 100 non-polio enteroviruses, is acid-labile and biologically similar to human rhinoviruses (HRV) (originally classified as HRV87). However, there is no approved preventive or therapeutic measure against EV-D68, HRV, or other enteroviruses. In this study, we evaluated the antiviral activity of series of dipeptidyl compounds against EV-D68 and HRV strains, and demonstrated that several peptidyl aldehyde and α-ketoamide peptidyl compounds are potent inhibitors of EV-D68 and HRV strains with high in-vitro therapeutic indices (>1000). One of the α-ketoamide compounds is shown to have favorable pharmacokinetics profiles, including a favorable oral bioavailability in rats. Recent successful development of α-ketoamide protease inhibitors against hepatitis C virus suggests these compounds may have a high potential for further optimization and development against emerging EV-D68, as well as HRV.",,"['Kim, Yunjeong', 'Galasiti Kankanamalage, Anushka C.', 'Damalanka, Vishnu C.', 'Weerawarna, Pathum M.', 'Groutas, William C.', 'Chang, Kyeong-Ok']",,,,
,PMC,Taking the bull by the horns: Ethical considerations in the design and implementation of an Ebola virus therapy trial,http://dx.doi.org/10.1016/j.socscimed.2015.11.017,PMC6858863,,,"Ebola virus is categorized as one of the most dangerous pathogens in the world. Although there is no known cure for Ebola virus, there is some evidence that the severity of the disease can be curtailed using plasma from survivors. Although there is a general consensus on the importance of research, methodological and ethical challenges for conducting research in an emergency situation have been identified. Performing clinical trials is important, especially for health conditions that are of public health significance (including rare epidemics) to develop new therapies as well as to test the efficacy and effectiveness of new interventions. However, routine clinical trial procedures can be difficult to apply in emergency public health crises hence require a consideration of alternative approaches on how therapies in these situations are tested and brought to the market. This paper examines some of the ethical issues that arise when conducting clinical trials during a highly dangerous pathogen outbreak, with a special focus on the Ebola virus outbreak in West Africa. The issues presented here come from a review of a protocol that was submitted to the Global Emerging Pathogens Treatment Consortium (GET). In reviewing the proposal, which was about conducting a clinical trial to evaluate the safety and efficacy of using convalescent plasma in the management of Ebola virus disease, the authors deliberated on various issues, which were documented as minutes and later used as a basis for this paper. The experiences and reflections shared by the authors, who came from different regions and disciplines across Africa, present wide-ranging perspectives on the conduct of clinical trials during a dangerous disease outbreak in a resource-poor setting.",,"['Kombe, Francis', 'Folayan, Morenike O.', 'Ambe, Jennyfer', 'Igonoh, Adaora', 'Abayomi, Akin']",,,,
,PMC,Anti-Ebola therapies based on monoclonal antibodies: Current state and challenges ahead,http://dx.doi.org/10.3109/07388551.2015.1114465,PMC5568563,,,"The 2014 Ebola outbreak, the largest recorded, took us largely unprepared, with no available vaccine or specific treatment. In this context, the World Health Organization (WHO) declared that the humanitarian use of experimental therapies against Ebola Virus (EBOV) is ethical. In particular, an experimental treatment consisting of a cocktail of three monoclonal antibodies (mAbs) produced in tobacco plants and specifically directed to the Ebola virus glycoprotein (GP) was tested in humans, apparently with good results. Several mAbs with high affinity to the GP have been described. This review discusses our current knowledge on this topic. Particular emphasis is devoted to those mAbs that have been assayed in animal models or humans as possible therapies against Ebola. Engineering aspects and challenges for the production of anti-Ebola mAbs are also briefly discussed; current platforms for the design and production of full-length mAbs are cumbersome and costly.",,"['González-González, E', 'Alvarez, MM', 'Márquez-Ipiña, AR', 'Santiago, G Trujillo-de', 'Rodríguez-Martínez, LM', 'Annabi, N', 'Khademhosseini, A']",,,,
,PMC,Identification of information types and sources by the public for promoting awareness of Middle East respiratory syndrome coronavirus in Saudi Arabia,http://dx.doi.org/10.1093/her/cyv061,PMC4883030,,,"Middle East Respiratory Syndrome (MERS) is a viral respiratory disease of serious consequences caused by MERS Coronavirus (MERS-CoV). Saudi communities still lack awareness of available protective measures to prevent the transmission of the virus. It is necessary to explore the current information-seeking strategies and preferences for communication tools among the Saudi population to promote dissemination of accurate information. Guided by McGuire’s Input–Output Persuasion Model and focusing on input variables (receiver characteristics, sources, message, channel and destination), we explored the current information-seeking strategies and preferences for different communication tools among residents of Riyadh (n = 658). Preferred and sought-after information sources on MERS. Most participants in the sample were female (61.7%), and the majority (98.2%) had internet access at home. The internet was the most commonly used source of information (39.5%) and the most endorsed channel for a MERS awareness campaign. Physicians were the preferred source of information (45.6%), followed by other health care providers (31.3%). In univariate multinomial logistic regression models, males and individuals aged ≤27 years were more likely to seek information from the internet than from physicians. Residents of southern and western Riyadh preferred physicians as a credible source of information over the Ministry of Health. The results of this survey provide valuable information on how to reach this population and for understanding how to launch an effective MERS risk communication campaign in a Saudi population.",,"Hoda, Jradi",,,,
,PMC,Identification of a resveratrol tetramer as a potent inhibitor of hepatitis C virus helicase,http://dx.doi.org/10.1111/bph.13358,PMC4813382,,,"BACKGROUND AND PURPOSE: Hepatitis C virus (HCV) infection is responsible for various chronic inflammatory liver diseases. Here, we have identified a naturally occurring compound with anti‐HCV activity and have elucidated its mode of antiviral action. EXPERIMENTAL APPROACH: Luciferase reporter and real‐time RT‐PCR assays were used to measure HCV replication. Western blot, fluorescence‐labelled HCV replicons and infectious clones were employed to quantitate expression levels of viral proteins. Resistant HCV mutant mapping, in vitro NS3 protease, helicase, NS5B polymerase and drug affinity responsive target stability assays were also used to study the antiviral mechanism. KEY RESULTS: A resveratrol tetramer, vitisin B from grapevine root extract showed high potency against HCV replication (EC(50) = 6 nM) with relatively low cytotoxicity (EC(50) >10 μM). Combined treatment of vitisin B with an NS5B polymerase inhibitor (sofosbuvir) exhibited a synergistic or at least additive antiviral activity. Analysis of a number of vitisin B‐resistant HCV variants suggested an NS3 helicase as its potential target. We confirmed a direct binding between vitisin B and a purified NS3 helicase in vitro. Vitisin B was a potent inhibitor of a HCV NS3 helicase (IC(50) = 3 nM). In vivo, Finally, we observed a preferred tissue distribution of vitisin B in the liver after i.p. injection in rats, at clinically attainable concentrations. Conclusion and Implications Vitisin B is one of the most potent HCV helicase inhibitors identified so far. Vitisin B is thus a prime candidate to be developed as the first HCV drug derived from natural products.",,"['Lee, Sungjin', 'Yoon, Kee Dong', 'Lee, Myungeun', 'Cho, Yoojin', 'Choi, Gahee', 'Jang, Hongje', 'Kim, BeomSeok', 'Jung, Da‐Hee', 'Oh, Jin‐Gyo', 'Kim, Geon‐Woo', 'Oh, Jong‐Won', 'Jeong, Yong‐Joo', 'Kwon, Ho Jeong', 'Bae, Soo Kyung', 'Min, Dal‐Hee', 'Windisch, Marc P', 'Heo, Tae‐Hwe', 'Lee, Choongho']",,,,
,PMC,Vaccination with a Porcine Reproductive and Respiratory Syndrome (PRRS) Modified Live Virus Vaccine Followed by Challenge with PRRS Virus and Porcine Circovirus Type 2 (PCV2) Protects against PRRS but Enhances PCV2 Replication and Pathogenesis Compared to Results for Nonvaccinated Cochallenged Controls,http://dx.doi.org/10.1128/CVI.00434-15,PMC4658591,,,"Coinfections involving porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) contribute to a group of disease syndromes known as porcine circovirus-associated disease (PCVAD). Presumably, PRRSV infection enhances PCV2 replication as a result of modulation of host immunity. The purpose of this study was to evaluate PCV2 replication and pathogenesis in pigs vaccinated with a PRRS modified live virus (MLV) vaccine and subsequently challenged with a combination of PRRSV and PCV2. During the early postchallenge period, the number of pigs with PRRSV-associated clinical signs was decreased, and average daily gain (ADG) was increased, in the vaccinated group, demonstrating the protective effect of PRRS vaccination. However, during the later postchallenge period, more pigs in the vaccinated group showed increased PCV2 viremia, decreased ADG, increased PCVAD clinical signs, and increased mortality. In this disease model, the early benefits of PRRSV vaccination were outweighed by the later amplification of PCVAD.",,"['Niederwerder, Megan C.', 'Bawa, Bhupinder', 'Serão, Nick V. L.', 'Trible, Benjamin R.', 'Kerrigan, Maureen A.', 'Lunney, Joan K.', 'Dekkers, Jack C. M.', 'Rowland, Raymond R. R.']",,,,
,PMC,"Discovery, Optimization, and Characterization of Novel Chlorcyclizine Derivatives for the Treatment of Hepatitis C Virus Infection",http://dx.doi.org/10.1021/acs.jmedchem.5b00752,PMC4753534,,,"[Image: see text] Recently, we reported that chlorcyclizine (CCZ, Rac-2), an over-the-counter antihistamine piperazine drug, possesses in vitro and in vivo activity against hepatitis C virus. Here, we describe structure–activity relationship (SAR) efforts that resulted in the optimization of novel chlorcyclizine derivatives as anti-HCV agents. Several compounds exhibited EC(50) values below 10 nM against HCV infection, cytotoxicity selectivity indices above 2000, and showed improved in vivo pharmacokinetic properties. The optimized molecules can serve as lead preclinical candidates for the treatment of hepatitis C virus infection and as probes to study hepatitis C virus pathogenesis and host–virus interaction.",,"['He, Shanshan', 'Xiao, Jingbo', 'Dulcey, Andrés E.', 'Lin, Billy', 'Rolt, Adam', 'Hu, Zongyi', 'Hu, Xin', 'Wang, Amy Q.', 'Xu, Xin', 'Southall, Noel', 'Ferrer, Marc', 'Zheng, Wei', 'Liang, T. Jake', 'Marugan, Juan J.']",,,,
,PMC,Household transmission of influenza virus,http://dx.doi.org/10.1016/j.tim.2015.10.012,PMC4733423,,,"Human influenza viruses cause regular epidemics and occasional pandemics with a substantial public health burden. Household transmission studies have provided valuable information on the dynamics of influenza transmission. We reviewed published studies and found that once one household member is infected with influenza, the risk of infection in a household contact can be up to 38%, and the delay between onset in index and secondary cases is around 3 days. Younger age was associated with higher susceptibility. In the future, household transmission studies will provide information on transmission dynamics including the correlation of virus shedding and symptoms with transmission, and the correlation of new measures of immunity with protection against infection.",,"['Tsang, Tim K.', 'Lau, Lincoln L. H.', 'Cauchemez, Simon', 'Cowling, Benjamin J.']",,,,
,PMC,iPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections,http://dx.doi.org/10.1021/acsmedchemlett.5b00318,PMC4716588,,,"[Image: see text] The Amaryllidaceae alkaloid trans-dihydrolycoricidine 7 and three analogues 8–10 were produced via asymmetric chemical synthesis. Alkaloid 7 proved superior to acyclovir, the current standard for herpes simplex virus, type 1 (HSV-1) infection. Compound 7 potently inhibited lytic HSV-1 infection, significantly reduced HSV-1 reactivation, and more potently inhibited varicella zoster virus (VZV) lytic infection. A configurationally defined (3R)-secondary alcohol at C3 proved crucial for efficacious inhibition of lytic HSV-1 infection.",,"['McNulty, James', 'D’Aiuto, Leonardo', 'Zhi, Yun', 'McClain, Lora', 'Zepeda-Velázquez, Carlos', 'Ler, Spencer', 'Jenkins, Hilary A.', 'Yee, Michael B.', 'Piazza, Paolo', 'Yolken, Robert H.', 'Kinchington, Paul R.', 'Nimgaonkar, Vishwajit L.']",,,,
,PMC,Serum Amyloid A Protein Concentration in Blood is Influenced by Genetic Differences in the Cheetah (Acinonyx jubatus),http://dx.doi.org/10.1093/jhered/esv089,PMC5994965,,,"Systemic amyloid A (AA) amyloidosis is a major cause of morbidity and mortality among captive cheetahs. The self-aggregating AA protein responsible for this disease is a byproduct of serum amyloid A (SAA) protein degradation. Transcriptional induction of the SAA1 gene is dependent on both C/EBPβ and NF-κB cis-acting elements within the promoter region. In cheetahs, 2 alleles exist for a single guanine nucleotide deletion in the putative NF-κB binding site. In this study, a novel genotyping assay was developed to screen for the alleles. The results show that the SAA1A(−97delG) allele is associated with decreased SAA protein concentrations in the serum of captive cheetahs (n = 58), suggesting genetic differences at this locus may be affecting AA amyloidosis prevalence. However, there was no significant difference in the frequency of the SAA1A(−97delG) allele between individuals confirmed AA amyloidosis positive versus AA amyloidosis negative at the time of necropsy (n = 48). Thus, even though there is evidence that having more copies of the SAA1A(−97delG) allele results in a potentially protective decrease in serum concentrations of SAA protein in captive cheetahs, genotype is not associated with this disease within the North American population. These results suggest that other factors are playing a more significant role in the pathogenesis of AA amyloidosis among captive cheetahs.",,"['Franklin, Ashley D', 'Schmidt-Küntzel, Anne', 'Terio, Karen A', 'Marker, Laurie L', 'Crosier, Adrienne E']",,,,
,PMC,FilmArray Respiratory Panel Assay: Comparison of Nasopharyngeal Swabs and Bronchoalveolar Lavage Samples,http://dx.doi.org/10.1128/JCM.01516-15,PMC4652125,,,"The FilmArray respiratory panel (FARP) reliably and rapidly identifies 17 viruses and 3 bacterial pathogens. A nasopharyngeal swab FARP (NP FARP) is performed for many patients with respiratory symptoms. For patients who are acutely ill or immunocompromised or fail to improve, a bronchoalveolar lavage sample FARP (BAL FARP) is performed in addition to the NP FARP. To date, no studies have compared the yield of a BAL FARP with that of an NP FARP. We retrospectively studied all patients who had a BAL FARP within 7 days after an NP FARP between June 2013 and May 2014. Demographic information, comorbidities, FARP results, and all microbiologic data from BAL fluid were collected. Eighty-six patients had a BAL FARP performed within 7 days (mean, 1.6; median, 1) after an NP FARP. Of these, 66 (77%) had concordant BAL and NP FARP results: 15 (23%) had the same pathogen identified from the NP and BAL FARPs, and 51 (77%) had concordant negative FARP results. In 18 of the 86 patients (21%), a pathogen was detected from the NP FARP; of these, 15 (83%) had a concordant match on a subsequent BAL FARP, and the remaining 3 had negative BAL FARPs. In 17 of the 86 patients (20%), pathogens were identified from the BAL FARPs that were not detected by the NP FARPs; of these, 16 (94%) had initial negative NP FARPs. The data suggest that once a pathogen is identified by an NP FARP, a subsequent BAL FARP is unlikely to add new microbiologic information. However, a BAL FARP may provide new, useful microbiologic information when performed within 7 days after a negative NP FARP.",,"['Azadeh, Natalya', 'Sakata, Kenneth K.', 'Brighton, Anjuli M.', 'Vikram, Holenarasipur R.', 'Grys, Thomas E.']",,,,
,PMC,Acinetobacter baumannii Extracellular OXA-58 Is Primarily and Selectively Released via Outer Membrane Vesicles after Sec-Dependent Periplasmic Translocation,http://dx.doi.org/10.1128/AAC.01343-15,PMC4649246,,,"Carbapenem-resistant Acinetobacter baumannii (CRAb) shelter cohabiting carbapenem-susceptible bacteria from carbapenem killing via extracellular release of carbapenem-hydrolyzing class D β-lactamases, including OXA-58. However, the mechanism of the extracellular release of OXA-58 has not been elucidated. In silico analysis predicted OXA-58 to be translocated to the periplasm via the Sec system. Using cell fractionation and Western blotting, OXA-58 with the signal peptide and C terminus deleted was not detected in the periplasmic and extracellular fractions. Overexpression of enhanced green fluorescent protein fused to the OXA-58 signal peptide led to its periplasmic translocation but not extracellular release, suggesting that OXA-58 is selectively released. The majority of the extracellular OXA-58 was associated with outer membrane vesicles (OMVs). The OMV-associated OXA-58 was detected only in a strain overexpressing OXA-58. The presence of OXA-58 in OMVs was confirmed by a carbapenem inactivation bioassay, proteomic analysis, and transmission electron microscopy. Imipenem treatment increased OMV formation and caused cell lysis, resulting in an increase in the OMV-associated and OMV-independent release of extracellular OXA-58. OMV-independent OXA-58 hydrolyzed nitrocefin more rapidly than OMV-associated OXA-58 but was more susceptible to proteinase K degradation. Rose bengal, an SecA inhibitor, inhibited the periplasmic translocation and OMV-associated release of OXA-58 and abolished the sheltering effect of CRAb. This study demonstrated that the majority of the extracellular OXA-58 is selectively released via OMVs after Sec-dependent periplasmic translocation. Addition of imipenem increased both OMV-associated and OMV-independent OXA-58, which may have different biological roles. SecA inhibitor could abolish the carbapenem-sheltering effect of CRAb.",,"['Liao, Yu-Ting', 'Kuo, Shu-Chen', 'Chiang, Ming-Hsien', 'Lee, Yi-Tzu', 'Sung, Wang-Chou', 'Chen, You-Hsuan', 'Chen, Te-Li', 'Fung, Chang-Phone']",,,,
,PMC,Biochemical Evaluation of the Inhibition Properties of Favipiravir and 2′-C-Methyl-Cytidine Triphosphates against Human and Mouse Norovirus RNA Polymerases,http://dx.doi.org/10.1128/AAC.01391-15,PMC4649231,,,"Norovirus (NoV) is a positive-sense single-stranded RNA virus that causes acute gastroenteritis and is responsible for 200,000 deaths per year worldwide. No effective vaccine or treatment is available. Recent studies have shown that the nucleoside analogs favipiravir (T-705) and 2′-C-methyl-cytidine (2CM-C) inhibit NoV replication in vitro and in animal models, but their precise mechanism of action is unknown. We evaluated the molecular interactions between nucleoside triphosphates and NoV RNA-dependent RNA polymerase (NoVpol), the enzyme responsible for replication and transcription of NoV genomic RNA. We found that T-705 ribonucleoside triphosphate (RTP) and 2CM-C triphosphate (2CM-CTP) equally inhibited human and mouse NoVpol activities at concentrations resulting in 50% of maximum inhibition (IC(50)s) in the low micromolar range. 2CM-CTP inhibited the viral polymerases by competing directly with natural CTP during primer elongation, whereas T-705 RTP competed mostly with ATP and GTP at the initiation and elongation steps. Incorporation of 2CM-CTP into viral RNA blocked subsequent RNA synthesis, whereas T-705 RTP did not cause immediate chain termination of NoVpol. 2CM-CTP and T-705 RTP displayed low levels of enzyme selectivity, as they were both recognized as substrates by human mitochondrial RNA polymerase. The level of discrimination by the human enzyme was increased with a novel analog of T-705 RTP containing a 2′-C-methyl substitution. Collectively, our data suggest that 2CM-C inhibits replication of NoV by acting as a classic chain terminator, while T-705 may inhibit the virus by multiple mechanisms of action. Understanding the precise mechanism of action of anti-NoV compounds could provide a rational basis for optimizing their inhibition potencies and selectivities.",,"['Jin, Zhinan', 'Tucker, Kathryn', 'Lin, Xiaoyan', 'Kao, C. Cheng', 'Shaw, Ken', 'Tan, Hua', 'Symons, Julian', 'Behera, Ishani', 'Rajwanshi, Vivek K.', 'Dyatkina, Natalia', 'Wang, Guangyi', 'Beigelman, Leo', 'Deval, Jerome']",,,,
,PMC,Molecular basis for specific viral RNA recognition and 2′-O-ribose methylation by the dengue virus nonstructural protein 5 (NS5),http://dx.doi.org/10.1073/pnas.1514978112,PMC4672796,,,"Dengue virus (DENV) causes several hundred million human infections and more than 20,000 deaths annually. Neither an efficacious vaccine conferring immunity against all four circulating serotypes nor specific drugs are currently available to treat this emerging global disease. Capping of the DENV RNA genome is an essential structural modification that protects the RNA from degradation by 5′ exoribonucleases, ensures efficient expression of viral proteins, and allows escape from the host innate immune response. The large flavivirus nonstructural protein 5 (NS5) (105 kDa) has RNA methyltransferase activities at its N-terminal region, which is responsible for capping the virus RNA genome. The methyl transfer reactions are thought to occur sequentially using the strictly conserved flavivirus 5′ RNA sequence as substrate (G(ppp)AG-RNA), leading to the formation of the 5′ RNA cap: G(0ppp)AG-RNA→(m7)G(0ppp)AG-RNA (“cap-0”)→(m7)G(0ppp)A(m2′-O-)G-RNA (“cap-1”). To elucidate how viral RNA is specifically recognized and methylated, we determined the crystal structure of a ternary complex between the full-length NS5 protein from dengue virus, an octameric cap-0 viral RNA substrate bearing the authentic DENV genomic sequence (5′-(m7)G(0ppp)A(1)G(2)U(3)U(4)G(5)U(6)U(7)-3′), and S-adenosyl-l-homocysteine (SAH), the by-product of the methylation reaction. The structure provides for the first time, to our knowledge, a molecular basis for specific adenosine 2′-O-methylation, rationalizes mutagenesis studies targeting the K61-D146-K180-E216 enzymatic tetrad as well as residues lining the RNA binding groove, and offers previously unidentified mechanistic and evolutionary insights into cap-1 formation by NS5, which underlies innate immunity evasion by flaviviruses.",,"['Zhao, Yongqian', 'Soh, Tingjin Sherryl', 'Lim, Siew Pheng', 'Chung, Ka Yan', 'Swaminathan, Kunchithapadam', 'Vasudevan, Subhash G.', 'Shi, Pei-Yong', 'Lescar, Julien', 'Luo, Dahai']",,,,
,PMC,Mechanisms of restriction of viral neuroinvasion at the blood-brain barrier,http://dx.doi.org/10.1016/j.coi.2015.10.008,PMC4715944,,,"The blood-brain barrier (BBB) consists of highly specialized cells including brain microvascular endothelial cells, astrocytes, microglia, pericytes, and neurons, which act in concert to restrict the entry of pathogens, immune cells, and soluble molecules into the central nervous system (CNS). If pathogens manage to cross the BBB and establish infection within the CNS, the BBB can open in a regulated manner to allow leukocyte transmigration into the CNS so that microbes, infected cells, and debris can be cleared. This review highlights how different inflammatory cytokines or signaling pathways disrupt or enhance BBB integrity in a way that regulates entry of neurotropic viruses into the CNS.",,"['Miner, Jonathan J.', 'Diamond, Michael S.']",,,,
,PMC,The Non-structural Protein of Crimean-Congo Hemorrhagic Fever Virus Disrupts the Mitochondrial Membrane Potential and Induces Apoptosis,http://dx.doi.org/10.1074/jbc.M115.667436,PMC4705379,,,"Viruses have developed distinct strategies to overcome the host defense system. Regulation of apoptosis in response to viral infection is important for virus survival and dissemination. Like other viruses, Crimean-Congo hemorrhagic fever virus (CCHFV) is known to regulate apoptosis. This study, for the first time, suggests that the non-structural protein NSs of CCHFV, a member of the genus Nairovirus, induces apoptosis. In this report, we demonstrated the expression of CCHFV NSs, which contains 150 amino acid residues, in CCHFV-infected cells. CCHFV NSs undergoes active degradation during infection. We further demonstrated that ectopic expression of CCHFV NSs induces apoptosis, as reflected by caspase-3/7 activity and cleaved poly(ADP-ribose) polymerase, in different cell lines that support CCHFV replication. Using specific inhibitors, we showed that CCHFV NSs induces apoptosis via both intrinsic and extrinsic pathways. The minimal active region of the CCHFV NSs protein was determined to be 93–140 amino acid residues. Using alanine scanning, we demonstrated that Leu-127 and Leu-135 are the key residues for NSs-induced apoptosis. Interestingly, CCHFV NSs co-localizes in mitochondria and also disrupts the mitochondrial membrane potential. We also demonstrated that Leu-127 and Leu-135 are important residues for disruption of the mitochondrial membrane potential by NSs. Therefore, these results indicate that the C terminus of CCHFV NSs triggers mitochondrial membrane permeabilization, leading to activation of caspases, which, ultimately, leads to apoptosis. Given that multiple factors contribute to apoptosis during CCHFV infection, further studies are needed to define the involvement of CCHFV NSs in regulating apoptosis in infected cells.",,"['Barnwal, Bhaskar', 'Karlberg, Helen', 'Mirazimi, Ali', 'Tan, Yee-Joo']",,,,
,PMC,The origin and onset of acute venous thrombus,,PMC4723736,,,"Under the condition of immune cell balancing function collapse, acute venous thrombosis originates from intravenous immune adhesive inflammations triggered by cells which are infected by foreign pathogenic microorganism and malignant cells. With the condition of immune cell balancing function collapse, the human body lost the function of clearing intravenous foreign pathogenic microorganism and malignant cells timely and effectively. Thus, integrins β2 and β3 on the membrane of white blood cells and platelets are activated to combine with the ligand fibrinogen into a reversible mesh-like structure, which is like the intravenous biological filter and acts as physical defense of the human body to prevent the cells which are infected by foreign pathogenic microorganism and malignant cells in the distal veins from flowing back to the whole body. Meanwhile, blood cells mainly red blood cells stagnate and fulfill the filter, which blocks the blood flow in the local veins and thus results in venous thrombotic diseases. People with collapsed immune cell balancing functions are the certain groups of people who will develop venous thromboembolism. Anyone who had venous thromboembolism indicates alloantigen cells in the veins, which are mainly pathogenic microorganism infected cells and malignant cells and trigger the onset of venous thromboembolism. Only under the condition of immune cell balancing function collapse, the risk factors, such as advanced age, infection, trauma, surgery, autoimmune disease, pregnancy as well as long trip syndrome, could cause venous thromboembolism.",,"['Wang, Lemin', 'Duan, Qianglin', 'Yang, Fan', 'Wen, Siwan']",,,,
,PMC,Replication-competent fluorescent-expressing influenza B virus,http://dx.doi.org/10.1016/j.virusres.2015.11.014,PMC5003614,,,"Influenza B viruses (IBVs) cause annual outbreaks of respiratory illness in humans and are increasingly recognized as a major cause of influenza-associated morbidity and mortality. Studying influenza viruses requires the use of secondary methodologies to identify virus-infected cells. To this end, replication-competent influenza A viruses (IAVs) expressing easily traceable fluorescent proteins have been recently developed. In contrast, similar approaches for IBV are mostly lacking. In this report, we describe the generation and characterization of replication-competent influenza B/Brisbane/60/2008 viruses expressing fluorescent mCherry or GFP fused to the C-terminal of the viral non-structural 1 (NS1) protein. Fluorescent-expressing IBVs display similar growth kinetics and plaque phenotype to wild-type IBV, while fluorescent protein expression allows for the easy identification of virus-infected cells. Without the need of secondary approaches to monitor viral infection, fluorescent-expressing IBVs represent an ideal approach to study the biology of IBV and an excellent platform for the rapid identification and characterization of antiviral therapeutics or neutralizing antibodies using high-throughput screening approaches. Lastly, fluorescent-expressing IBVs can be combined with the recently described reporter-expressing IAVs for the identification of novel therapeutics to combat these two important human respiratory pathogens.",,"['Nogales, Aitor', 'Rodríguez-Sánchez, Irene', 'Monte, Kristen', 'Lenschow, Deborah J.', 'Perez, Daniel R.', 'Martínez-Sobrido, Luis']",,,,
,PMC,Prone position for acute respiratory failure in adults,http://dx.doi.org/10.1002/14651858.CD008095.pub2,PMC6464920,,,"BACKGROUND: Acute hypoxaemia de novo or on a background of chronic hypoxaemia is a common reason for admission to intensive care and for provision of mechanical ventilation. Various refinements of mechanical ventilation or adjuncts are employed to improve patient outcomes. Mortality from acute respiratory distress syndrome, one of the main contributors to the need for mechanical ventilation for hypoxaemia, remains approximately 40%. Ventilation in the prone position may improve lung mechanics and gas exchange and could improve outcomes. OBJECTIVES: The objectives of this review are (1) to ascertain whether prone ventilation offers a mortality advantage when compared with traditional supine or semi recumbent ventilation in patients with severe acute respiratory failure requiring conventional invasive artificial ventilation, and (2) to supplement previous systematic reviews on prone ventilation for hypoxaemic respiratory failure in an adult population. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 1), Ovid MEDLINE (1950 to 31 January 2014), EMBASE (1980 to 31 January 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 31 January 2014) and Latin American Caribbean Health Sciences Literature (LILACS) (1992 to 31 January 2014) in Ovid MEDLINE for eligible randomized controlled trials. We also searched for studies by handsearching reference lists of relevant articles, by contacting colleagues and by handsearching published proceedings of relevant journals. We applied no language constraints, and we reran the searches in CENTRAL, MEDLINE, EMBASE, CINAHL and LILACS in June 2015. We added five new studies of potential interest to the list of ""Studies awaiting classification"" and will incorporate them into formal review findings during the review update. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that examined the effects of prone position versus supine/semi recumbent position during conventional mechanical ventilation in adult participants with acute hypoxaemia. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed all trials identified by the search and assessed them for suitability, methods and quality. Two review authors extracted data, and three review authors reviewed the data extracted. We analysed data using Review Manager software and pooled included studies to determine the risk ratio (RR) for mortality and the risk ratio or mean difference (MD) for secondary outcomes; we also performed subgroup analyses and sensitivity analyses. MAIN RESULTS: We identified nine relevant RCTs, which enrolled a total of 2165 participants (10 publications). All recruited participants suffered from disorders of lung function causing moderate to severe hypoxaemia and requiring mechanical ventilation, so they were fairly comparable, given the heterogeneity of specific disease diagnoses in intensive care. Risk of bias, although acceptable in the view of the review authors, was inevitable: Blinding of participants and carers to treatment allocation was not possible (face‐up vs face‐down). Primary analyses of short‐ and longer‐term mortality pooled from six trials demonstrated an RR of 0.84 to 0.86 in favour of the prone position (PP), but findings were not statistically significant: In the short term, mortality for those ventilated prone was 33.4% (363/1086) and supine 38.3% (395/1031). This resulted in an RR of 0.84 (95% confidence interval (CI) 0.69 to 1.02) marginally in favour of PP. For longer‐term mortality, results showed 41.7% (462/1107) for prone and 47.1% (490/1041) for supine positions, with an RR of 0.86 (95% CI 0.72 to 1.03). The quality of the evidence for both outcomes was rated as low as a result of important potential bias and serious inconsistency. Subgroup analyses for mortality identified three groups consistently favouring PP: those recruited within 48 hours of meeting entry criteria (five trials; 1024 participants showed an RR of 0.75 (95% CI 0.59 to 94)); those treated in the PP for 16 or more hours per day (five trials; 1005 participants showed an RR of 0.77 (95% CI 0.61 to 0.99)); and participants with more severe hypoxaemia at trial entry (six trials; 1108 participants showed an RR of 0.77 (95% CI 0.65 to 0.92)). The quality of the evidence for these outcomes was rated as moderate as a result of potentially important bias. Prone positioning appeared to influence adverse effects: Pressure sores (three trials; 366 participants) with an RR of 1.37 (95% CI 1.05 to 1.79) and tracheal tube obstruction with an RR of 1.78 (95% CI 1.22 to 2.60) were increased with prone ventilation. Reporting of arrhythmias was reduced with PP, with an RR of 0.64 (95% CI 0.47 to 0.87). AUTHORS' CONCLUSIONS: We found no convincing evidence of benefit nor harm from universal application of PP in adults with hypoxaemia mechanically ventilated in intensive care units (ICUs). Three subgroups (early implementation of PP, prolonged adoption of PP and severe hypoxaemia at study entry) suggested that prone positioning may confer a statistically significant mortality advantage. Additional adequately powered studies would be required to confirm or refute these possibilities of subgroup benefit but are unlikely, given results of the most recent study and recommendations derived from several published subgroup analyses. Meta‐analysis of individual patient data could be useful for further data exploration in this regard. Complications such as tracheal obstruction are increased with use of prone ventilation. Long‐term mortality data (12 months and beyond), as well as functional, neuro‐psychological and quality of life data, are required if future studies are to better inform the role of PP in the management of hypoxaemic respiratory failure in the ICU.",,"['Bloomfield, Roxanna', 'Noble, David W', 'Sudlow, Alexis']",,,,
,PMC,Global Transcriptional Profiling of Diapause and Climatic Adaptation in Drosophila melanogaster,http://dx.doi.org/10.1093/molbev/msv263,PMC5009998,,,"Wild populations of the model organism Drosophila melanogaster experience highly heterogeneous environments over broad geographical ranges as well as over seasonal and annual timescales. Diapause is a primary adaptation to environmental heterogeneity, and in D. melanogaster the propensity to enter diapause varies predictably with latitude and season. Here we performed global transcriptomic profiling of naturally occurring variation in diapause expression elicited by short day photoperiod and moderately low temperature in two tissue types associated with neuroendocrine and endocrine signaling, heads, and ovaries. We show that diapause in D. melanogaster is an actively regulated phenotype at the transcriptional level, suggesting that diapause is not a simple physiological or reproductive quiescence. Differentially expressed genes and pathways are highly distinct in heads and ovaries, demonstrating that the diapause response is not uniform throughout the soma and suggesting that it may be comprised of functional modules associated with specific tissues. Genes downregulated in heads of diapausing flies are significantly enriched for clinally varying single nucleotide polymorphism (SNPs) and seasonally oscillating SNPs, consistent with the hypothesis that diapause is a driving phenotype of climatic adaptation. We also show that chromosome location-based coregulation of gene expression is present in the transcriptional regulation of diapause. Taken together, these results demonstrate that diapause is a complex phenotype actively regulated in multiple tissues, and support the hypothesis that natural variation in diapause propensity underlies adaptation to spatially and temporally varying selective pressures.",,"['Zhao, Xiaqing', 'Bergland, Alan O.', 'Behrman, Emily L.', 'Gregory, Brian D.', 'Petrov, Dmitri A.', 'Schmidt, Paul S.']",,,,
,PMC,Symptomatic Respiratory Virus Infection and Chronic Lung Allograft Dysfunction,http://dx.doi.org/10.1093/cid/civ871,PMC4706632,,,"Background. Chronic lung allograft dysfunction (CLAD) is a major cause of allograft loss post-lung transplantation. Prior studies have examined the association between respiratory virus infection (RVI) and CLAD were limited by older diagnostic techniques, study design, and case numbers. We examined the association between symptomatic RVI and CLAD using modern diagnostic techniques in a large contemporary cohort of lung transplant recipients (LTRs). Methods. We retrospectively assessed clinical variables including acute rejection, cytomegalovirus pneumonia, upper and lower RVI, and the primary endpoint of CLAD (determined by 2 independent reviewers) in 250 LTRs in a single university transplantation program. Univariate and multivariate Cox models were used to analyze the relationship between RVI and CLAD in a time-dependent manner, incorporating different periods of risk following RVI diagnosis. Results. Fifty patients (20%) were diagnosed with CLAD at a median of 95 weeks post-transplantation, and 79 (32%) had 114 episodes of RVI. In multivariate analysis, rejection and RVI were independently associated with CLAD (adjusted hazard ratio [95% confidence interval]) 2.2 (1.2–3.9), P = .01 and 1.9 (1.1–3.5), P = .03, respectively. The association of RVI with CLAD was stronger the more proximate the RVI episode: 4.8 (1.9–11.6), P < .01; 3.4 (1.5–7.5), P < .01; and 2.4 (1.2–5.0), P = .02 in multivariate analysis for 3, 6, and 12 months following RVI, respectively. Conclusions. Symptomatic RVI is independently associated with development of CLAD, with increased risk at shorter time periods following RVI. Prospective studies to characterize the virologic determinants of CLAD and define the underlying mechanisms are warranted.",,"['Fisher, Cynthia E.', 'Preiksaitis, Carl M.', 'Lease, Erika D.', 'Edelman, Jeffrey', 'Kirby, Katharine A.', 'Leisenring, Wendy M.', 'Raghu, Ganesh', 'Boeckh, Michael', 'Limaye, Ajit P.']",,,,
,PMC,Viral quantity and pathological changes in broilers experimentally infected by IRFIBV32 isolate of infectious bronchitis virus,http://dx.doi.org/10.1007/s13337-015-0286-4,PMC4663706,,,"An Iranian isolate of avian infectious bronchitis virus IRFIBV32 was quantified in experimentally infected broilers using real-time reverse transcriptase polymerase chain reaction and histopathological changes was investigated. Thirty-six 3-week-old commercial broilers were inoculated by 10(5) ELD50/0.1 ml of the virus. On the various days post inoculation (dpi) different tissues were collected. The virus strongly started the replication in trachea at 1 dpi and reached to the maximum titer at 3 dpi. The highest IBV RNA level was shown in this organ. In lung, the virus was replicated with the titer lower than that of the trachea, but it rose up more at 5 dpi. The kidneys were the tissues with the least viral genome copy number, although the duration of the virus presence was considerable. The virus replicated in testes sooner than ovaries also disappeared sooner but the maximum viral yield in the ovaries was more. The virus titer in the studied tissues had an interesting fluctuation especially in caecal tonsils. Testes and ovaries were the organs that the virus could reactivate without using any chemical. The most severe lesions were observed in tracheae but they appeared in the lungs later. Lymphocyte infiltration in the kidneys was noted from 5 dpi even sooner than the lungs. There were no lesions in the caecal tonsils, testes and ovaries in spite of the virus replication in a high titer.",,"['Mohammadi, Ali', 'Asasi, Keramat', 'Boroomand, Zahra', 'Namazi, Fatemeh', 'Hosseinian, Seyedeh Alemeh']",,,,
,PMC,The sweet side of RNA regulation: glyceraldehyde-3-phosphate dehydrogenase as a noncanonical RNA-binding protein,http://dx.doi.org/10.1002/wrna.1315,PMC5120886,,,"The glycolytic protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), has a vast array of extraglycolytic cellular functions, including interactions with nucleic acids. GAPDH has been implicated in the translocation of transfer RNA (tRNA), the regulation of cellular messenger RNA (mRNA) stability and translation, as well as the regulation of replication and gene expression of many single-stranded RNA viruses. A growing body of evidence supports GAPDH–RNA interactions serving as part of a larger coordination between intermediary metabolism and RNA biogenesis. Despite the established role of GAPDH in nucleic acid regulation, it is still unclear how and where GAPDH binds to its RNA targets, highlighted by the absence of any conserved RNA-binding sequences. This review will summarize our current understanding of GAPDH-mediated regulation of RNA function.",,"['White, Michael R.', 'Garcin, Elsa D.']",,,,
,PMC,"Elements of successful management of an imported Middle East respiratory syndrome case in Guangdong, China",http://dx.doi.org/10.5365/WPSAR.2015.6.4.001,PMC4712532,,,,,"['Song, Tie', 'Kang, Min', 'Zhang, Yonghui', 'Liang, Lihuan', 'Lin, Hualiang']",,,,
,PMC,Smad7 Protein Interacts with Receptor-regulated Smads (R-Smads) to Inhibit Transforming Growth Factor-β (TGF-β)/Smad Signaling,http://dx.doi.org/10.1074/jbc.M115.694281,PMC4697173,,,"TGF-β is a pleiotropic cytokine that regulates a wide range of cellular actions and pathophysiological processes. TGF-β signaling is spatiotemporally fine-tuned. As a key negative regulator of TGF-β signaling, Smad7 exerts its inhibitory effects by blocking receptor activity, inducing receptor degradation or interfering with Smad-DNA binding. However, the functions and the molecular mechanisms underlying the actions of Smad7 in TGF-β signaling are still not fully understood. In this study we report a novel mechanism whereby Smad7 antagonizes TGF-β signaling at the Smad level. Smad7 oligomerized with R-Smad proteins upon TGF-β signaling and directly inhibited R-Smad activity, as assessed by Gal4-luciferase reporter assays. Mechanistically, Smad7 competes with Smad4 to associate with R-Smads and recruits the E3 ubiquitin ligase NEDD4L to activated R-Smads, leading to their polyubiquitination and proteasomal degradation. Similar to the R-Smad-Smad4 oligomerization, the interaction between R-Smads and Smad7 is mediated by their mad homology 2 (MH2) domains. A positive-charged basic region including the L3/β8 loop-strand module and adjacent amino acids in the MH2 domain of Smad7 is essential for the interaction. These results shed new light on the regulation of TGF-β signaling by Smad7.",,"['Yan, Xiaohua', 'Liao, Hongwei', 'Cheng, Minzhang', 'Shi, Xiaojing', 'Lin, Xia', 'Feng, Xin-Hua', 'Chen, Ye-Guang']",,,,
,PMC,SARS-like cluster of circulating bat coronavirus pose threat for human emergence,http://dx.doi.org/10.1038/nm.3985,PMC4797993,,,"The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. In this study, we examine the disease potential for SARS-like CoVs currently circulating in Chinese horseshoe bat populations. Utilizing the SARS-CoV infectious clone, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild type backbone can efficiently utilize multiple ACE2 receptor orthologs, replicate efficiently in primary human airway cells, and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from CoVs utilizing the novel spike protein. Importantly, based on these findings, we synthetically rederived an infectious full length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Together, the work highlights a continued risk of SARS-CoV reemergence from viruses currently circulating in bat populations.",,"['Menachery, Vineet D.', 'Yount, Boyd L.', 'Debbink, Kari', 'Agnihothram, Sudhakar', 'Gralinski, Lisa E.', 'Plante, Jessica A.', 'Graham, Rachel L.', 'Scobey, Trevor', 'Ge, Xing-Yi', 'Donaldson, Eric F.', 'Randell, Scott H.', 'Lanzavecchia, Antonio', 'Marasco, Wayne A.', 'Shi, Zhengli-Li', 'Baric, Ralph S.']",,,,
,PMC,Use of corticosteroids during acute phase of Kawasaki disease,http://dx.doi.org/10.5409/wjcp.v4.i4.135,PMC4637804,,,"In spite of initial intravenous immunoglobulin (IVIG) treatment, a significant number of patients are unresponsive to it and are at a higher risk for coronary artery lesions. Corticosteroids have been used as a secondary drug or used in combination with IVIG. Three options of using corticosteroids for the treatment of patients during the acute phase of Kawasaki disease, have been considered. The first is their use exclusively for patients unresponsive to IVIG treatment. The second is their use in combination with IVIG as the routine first line therapy for all patients. The last is the use in the combination as the first line therapy for selected patients at a high risk being unresponsive to initial IVIG. However, it is uncertain that the corticosteroids as the second line treatment are better than the additional IVIG in patients unresponsive to initial IVIG. The combination of corticosteroids and IVIG as the routine first line therapy also have not enough evidences. The last option of using corticosteroids - the combination of corticosteroids and IVIG in patients at high risk of unresponsiveness, is a properly reasonable treatment strategy. However, there have been no globally standardized predictive models for the unresponsiveness to initial IVIG treatment. Therefore, future investigations to determine the best predictive model are necessary.",,"Yu, Jeong Jin",,,,
,PMC,Antiviral Cystine Knot α-Amylase Inhibitors from Alstonia scholaris,http://dx.doi.org/10.1074/jbc.M115.654855,PMC4692237,,,"Cystine knot α-amylase inhibitors are cysteine-rich, proline-rich peptides found in the Amaranthaceae and Apocynaceae plant species. They are characterized by a pseudocyclic backbone with two to four prolines and three disulfides arranged in a knotted motif. Similar to other knottins, cystine knot α-amylase inhibitors are highly resistant to degradation by heat and protease treatments. Thus far, only the α-amylase inhibition activity has been described for members of this family. Here, we show that cystine knot α-amylase inhibitors named alstotides discovered from the Alstonia scholaris plant of the Apocynaceae family display antiviral activity. The alstotides (As1–As4) were characterized by both proteomic and genomic methods. All four alsotides are novel, heat-stable and enzyme-stable and contain 30 residues. NMR determination of As1 and As4 structures reveals their conserved structural fold and the presence of one or more cis-proline bonds, characteristics shared by other cystine knot α-amylase inhibitors. Genomic analysis showed that they contain a three-domain precursor, an arrangement common to other knottins. We also showed that alstotides are antiviral and cell-permeable to inhibit the early phase of infectious bronchitis virus and Dengue infection, in addition to their ability to inhibit α-amylase. Taken together, our results expand membership of cystine knot α-amylase inhibitors in the Apocynaceae family and their bioactivity, functional promiscuity that could be exploited as leads in developing therapeutics.",,"['Nguyen, Phuong Quoc Thuc', 'Ooi, Justin Seng Geap', 'Nguyen, Ngan Thi Kim', 'Wang, Shujing', 'Huang, Mei', 'Liu, Ding Xiang', 'Tam, James P.']",,,,
,PMC,Analyses of Merging Clinical and Viral Genetic Data for Influenza Surveillance,,PMC4765576,,,"The annual influenza vaccine is one of the most common public health interventions and is universally recommended for all individuals older than six months. Vaccine composition depends on viruses circulating over the past flu season and are estimated to be the most prevalent and representative strains in the current season. Here, we use clinical data outfitted with viral genetics to characterize confirmed influenza cases from the past two flu seasons and genetically compare them to the strains that they were vaccinated against that year. We show that case similarities to vaccine strains differ by geographic region and that the vaccines appear to have different levels of effectiveness by region. This study demonstrates the value of merging viral genetics with clinical data. Further research is needed to formally evaluate whether this improves biosurveillance efforts and enhances efficacy of influenza vaccines.",,"['Magee, Daniel', 'Beard, Rachel', 'Scotch, Matthew']",,,,
,PMC,Precision Public Health for the Era of Precision Medicine,http://dx.doi.org/10.1016/j.amepre.2015.08.031,PMC4915347,,,,,"['Khoury, Muin J.', 'Iademarco, Michael F.', 'Riley, William T.']",,,,
,PMC,Human Coronavirus-Associated Influenza-Like Illness in the Community Setting in Peru,http://dx.doi.org/10.4269/ajtmh.15-0271,PMC4703274,,,"We present findings describing the epidemiology of non-severe acute respiratory syndrome human coronavirus-associated influenza-like illness from a population-based active follow-up study in four different regions of Peru. In 2010, the prevalence of infections by human coronaviruses 229E, OC43, NL63, or HKU1 was 6.4% in participants with influenza-like illness who tested negative for influenza viruses. Ten of 11 human coronavirus infections were identified in the fall–winter season. Human coronaviruses are present in different regions of Peru and are relatively frequently associated with influenza-like illness in Peru.",,"['Razuri, Hugo', 'Malecki, Monika', 'Tinoco, Yeny', 'Ortiz, Ernesto', 'Guezala, M. Claudia', 'Romero, Candice', 'Estela, Abel', 'Breña, Patricia', 'Morales, Maria-Luisa', 'Reaves, Erik J.', 'Gomez, Jorge', 'Uyeki, Timothy M.', 'Widdowson, Marc-Alain', 'Azziz-Baumgartner, Eduardo', 'Bausch, Daniel G.', 'Schildgen, Verena', 'Schildgen, Oliver', 'Montgomery, Joel M.']",,,,
,PMC,A gene deletion that up-regulates viral gene expression yields an attenuated RSV vaccine with improved antibody responses in children,http://dx.doi.org/10.1126/scitranslmed.aac8463,PMC6342448,,,"Respiratory syncytial virus (RSV) is the leading viral cause of severe pediatric respiratory illness, and a safe and effective vaccine for use in infancy and early childhood is needed. We previously showed that deletion of the coding sequence for the viral M2–2 protein (ΔM2–2) down-regulated viral RNA replication and up-regulated gene transcription and antigen synthesis, raising the possibility of development of an attenuated vaccine with enhanced immunogenicity. RSV MEDI ΔM2–2 was therefore evaluated as a live intranasal vaccine in adults, RSV-seropositive children, and RSV-seronegative children. When results in RSV-seronegative children were compared to those achieved with the previous leading live attenuated RSV candidate vaccine, vaccine virus shedding was significantly more restricted, yet the post-vaccination RSV-neutralizing serum antibody achieved [geometric mean titer (GMT) = 1:97] was significantly greater. Surveillance during the subsequent RSV season showed that several seronegative RSV MEDI ΔM2–2 recipients had substantial antibody rises without reported illness, suggesting that the vaccine was protective yet primed for anamnestic responses to RSV. Rational design appears to have yielded a candidate RSV vaccine that is intrinsically superior at eliciting protective antibody in RSV-nai’ve children and highlights an approach for the development of live attenuated RSV vaccines.",,"['Karron, Ruth A.', 'Luongo, Cindy', 'Thumar, Bhagvanji', 'Loehr, Karen M.', 'Englund, Janet A.', 'Collins, Peter L.', 'Buchholz, Ursula J.']",,,,
,PMC,UNIT 14A.4 Generation of Recombinant Vaccinia Viruses,http://dx.doi.org/10.1002/9780471729259.mc14a04s39,PMC5123791,,,"This unit describes how to infect cells with vaccinia virus and then transfect them with a plasmid-transfer vector or PCR fragment to generate a recombinant virus. Selection and screening methods used to isolate recombinant viruses and a method for the amplification of recombinant viruses are described. Finally, a method for live immunostaining that has been used primarily for detection of recombinant modified vaccinia virus Ankara (MVA) is presented. This unit first describes how to infect cells with vaccinia virus and then transfect them with a plasmid-transfer vector or PCR fragment to generate a recombinant virus (see Basic Protocol 1). Also presented are selection and screening methods used to isolate recombinant viruses (see Basic Protocol 2) and a method for the amplification of recombinant viruses (see Basic Protocol 3). Finally, a method for live immunostaining that has been used primarily for detection of recombinant modified vaccinia virus Ankara (MVA) is presented (see Basic Protocol 4). HeLa S3 cells are recommended for large-scale growth of vaccinia virus. BS-C-1 cells may be used for xanthine-guanine phosphoribosyltransferase (XGPRT) and plaque size selection, fluorescent protein screening, transfection and determination of virus titer (UNIT 14A.3). For thymidine kinase (TK) selection, HuTK(−) 143B cells are used. With MVA, all steps are carried out in CEF or BHK-21 cells (UNIT 14A.3). CAUTION: Proceed carefully and follow biosafety level 2 (BL-2) practices when working with standard vaccinia virus (see UNIT 14A.3 for safety precautions). [*Copy Editor: The original CPMB unit referenced CPMB Unit 16.15 for safety. The chapter editor asked that the authors include some of the safety information in the revised units – CPMB 16.16 and 16.17 – which are now CPMC Unit 14A.3 and 14A.4. As a result, the authors changed the safety citation here to “Unit 14A.3”, which doesn’t have nearly as much information as the original CPMB Unit 16.15. Perhaps the reason is that some of those early safety concerns are no longer relevant, but it would be good if you could double check with the authors and ask why they elected not to add more safety information. If guidelines have been relaxed in the pox virus field, that would be good to say explicitly.] NOTE: Carry out all procedures for preparation of virus in a biosafety cabinet.",,"['Earl, Patricia L.', 'Moss, Bernard', 'Wyatt, Linda S.']",,,,
,PMC,Redefining the BH3 death domain as a “Short Linear Motif”,http://dx.doi.org/10.1016/j.tibs.2015.09.007,PMC5056427,,,"BCL-2-related proteins control programmed cell death through a complex network of protein-protein interactions mediated by BCL-2 homology 3 (BH3) domains. Given their roles as dynamic linchpins, the discovery of novel BH3-containing proteins has attracted considerable attention. However, without a clearly defined BH3 signature sequence, the BCL-2 family has expanded to include a nebulous group of non-homologous BH3-only proteins, now justified by an intriguing twist. We present evidence that BH3s from both ordered and disordered proteins represent a new class of short linear motifs (SLiMs) or molecular recognition features (MoRFs), and are diverse in their evolutionary histories. The implied corollaries are that BH3s have a broad phylogenetic distribution and could potentially bind to non-BCL-2-like structural domains with distinct functions.",,"['Aouacheria, Abdel', 'Combet, Christophe', 'Tompa, Peter', 'Hardwick, J. Marie']",,,,
,PMC,Chemical Modulation of Endocytic Sorting Augments Adeno-associated Viral Transduction,http://dx.doi.org/10.1074/jbc.M115.687657,PMC4705411,,,"Intracellular trafficking of viruses can be influenced by a variety of inter-connected cellular sorting and degradation pathways involving endo-lysosomal vesicles, the ubiquitin-proteasome system, and autophagy-based or endoplasmic reticulum-associated machinery. In the case of recombinant adeno-associated viruses (AAV), proteasome inhibitors are known to prevent degradation of ubiquitinated AAV capsids, thereby leading to increased nuclear accumulation and transduction. However, the impact of other cellular degradation pathways on AAV trafficking is not well understood. In the current study, we screened a panel of small molecules focused on modulating different cellular degradation pathways and identified eeyarestatin I (EerI) as a novel reagent that enhances AAV transduction. EerI improved AAV transduction by an order of magnitude regardless of vector dose, genome architecture, cell type, or serotype. This effect was preceded by sequestration of AAV within enlarged vesicles that were dispersed throughout the cytoplasm. Specifically, EerI treatment redirected AAV particles toward large vesicles positive for late endosomal (Rab7) and lysosomal (LAMP1) markers. Notably, MG132 and EerI (proteasomal and endoplasmic reticulum-associated degradation inhibitors, respectively) appear to enhance AAV transduction by increasing the intracellular accumulation of viral particles in a mutually exclusive fashion. Taken together, our results expand on potential strategies to redirect recombinant AAV vectors toward more productive trafficking pathways by deregulating cellular degradation mechanisms.",,"['Berry, Garrett E.', 'Asokan, Aravind']",,,,
,PMC,Evolutionary origins of hepatitis A virus in small mammals,http://dx.doi.org/10.1073/pnas.1516992112,PMC4679062,,,"Hepatitis A virus (HAV) is an ancient and ubiquitous human pathogen recovered previously only from primates. The sole species of the genus Hepatovirus, existing in both enveloped and nonenveloped forms, and with a capsid structure intermediate between that of insect viruses and mammalian picornaviruses, HAV is enigmatic in its origins. We conducted a targeted search for hepatoviruses in 15,987 specimens collected from 209 small mammal species globally and discovered highly diversified viruses in bats, rodents, hedgehogs, and shrews, which by pairwise sequence distance comprise 13 novel Hepatovirus species. Near-complete genomes from nine of these species show conservation of unique hepatovirus features, including predicted internal ribosome entry site structure, a truncated VP4 capsid protein lacking N-terminal myristoylation, a carboxyl-terminal pX extension of VP1, VP2 late domains involved in membrane envelopment, and a cis-acting replication element within the 3D(pol) sequence. Antibodies in some bat sera immunoprecipitated and neutralized human HAV, suggesting conservation of critical antigenic determinants. Limited phylogenetic cosegregation among hepatoviruses and their hosts and recombination patterns are indicative of major hepatovirus host shifts in the past. Ancestral state reconstructions suggest a Hepatovirus origin in small insectivorous mammals and a rodent origin of human HAV. Patterns of infection in small mammals mimicked those of human HAV in hepatotropism, fecal shedding, acute nature, and extinction of the virus in a closed host population. The evolutionary conservation of hepatovirus structure and pathogenesis provide novel insight into the origins of HAV and highlight the utility of analyzing animal reservoirs for risk assessment of emerging viruses.",,"['Drexler, Jan Felix', 'Corman, Victor M.', 'Lukashev, Alexander N.', 'van den Brand, Judith M. A.', 'Gmyl, Anatoly P.', 'Brünink, Sebastian', 'Rasche, Andrea', 'Seggewiβ, Nicole', 'Feng, Hui', 'Leijten, Lonneke M.', 'Vallo, Peter', 'Kuiken, Thijs', 'Dotzauer, Andreas', 'Ulrich, Rainer G.', 'Lemon, Stanley M.', 'Drosten, Christian', None]",,,,
,PMC,Role of Signal Transducer and Activator of Transcription 1 in Murine Allergen–Induced Airway Remodeling and Exacerbation by Carbon Nanotubes,http://dx.doi.org/10.1165/rcmb.2014-0221OC,PMC4742949,,,"Asthma is characterized by a T helper type 2 phenotype and by chronic allergen-induced airway inflammation (AAI). Environmental exposure to air pollution ultrafine particles (i.e., nanoparticles) exacerbates AAI, and a concern is possible exacerbation posed by engineered nanoparticles generated by emerging nanotechnologies. Signal transducer and activator of transcription (STAT) 1 is a transcription factor that maintains T helper type 1 cell development. However, the role of STAT1 in regulating AAI or exacerbation by nanoparticles has not been explored. In this study, mice with whole-body knockout of the Stat1 gene (Stat1(−/−)) or wild-type (WT) mice were sensitized to ovalbumin (OVA) allergen and then exposed to multiwalled carbon nanotubes (MWCNTs) by oropharygneal aspiration. In Stat1(−/−) and WT mice, OVA increased eosinophils in bronchoalveolar lavage fluid, whereas MWCNTs increased neutrophils. Interestingly, OVA sensitization prevented MWCNT-induced neutrophilia and caused only eosinophilic inflammation. Stat1(−/−) mice displayed increased IL-13 in bronchoalveolar lavage fluid at 1 day compared with WT mice after treatment with OVA or OVA and MWCNTs. At 21 days, the lungs of OVA-sensitized Stat1(−/−) mice displayed increased eosinophilia, goblet cell hyperplasia, airway fibrosis, and subepithelial apoptosis. MWCNTs further increased OVA-induced goblet cell hyperplasia, airway fibrosis, and apoptosis in Stat1(−/−) mice at 21 days. These changes corresponded to increased levels of profibrogenic mediators (transforming growth factor-β1, TNF-α, osteopontin) but decreased IL-10 in Stat1(−/−) mice. Finally, fibroblasts isolated from the lungs of Stat1(−/−) mice produced significantly more collagen mRNA and protein in response to transforming growth factor-β1 compared with WT lung fibroblasts. Our results support a protective role for STAT1 in chronic AAI and exacerbation of remodeling caused by MWCNTs.",,"['Thompson, Elizabeth A.', 'Sayers, Brian C.', 'Glista-Baker, Ellen E.', 'Shipkowski, Kelly A.', 'Ihrie, Mark D.', 'Duke, Katherine S.', 'Taylor, Alexia J.', 'Bonner, James C.']",,,,
,PMC,Virus/Allergen Interaction in Asthma Exacerbation,http://dx.doi.org/10.1513/AnnalsATS.201503-153AW,PMC4722838,,,"Allergy and viral respiratory infections have long been recognized as two of the most important risk factors for exacerbations of asthma. These observations have raised questions regarding potential interactions between these two important risk factors. For example, does allergy diminish the antiviral response, thereby promoting exacerbations of asthma? Alternately, do viral respiratory infections potentiate ongoing allergic inflammation in the airway? The answers to these questions are likely to have implications regarding the prevention and treatment of exacerbations of asthma. This article reviews that clinical evidence linking viral infections and allergy to exacerbations of asthma, reviews potential interactions between these two risk factors, and discusses possible application of new insights in virus/allergen interactions to the prevention and treatment of exacerbations of asthma.",,"Gern, James E.",,,,
,PMC,Viruses in Idiopathic Pulmonary Fibrosis. Etiology and Exacerbation,http://dx.doi.org/10.1513/AnnalsATS.201502-088AW,PMC4722834,,,"Viral infections are important contributors to exacerbation of asthma and chronic obstructive pulmonary disease; however, the role of viruses in the pathogenesis of idiopathic pulmonary fibrosis (IPF) is less clear. This likely reflects that fact that IPF acute exacerbations are defined clinically as “noninfectious,” and little attention has been paid to the outcomes of patients with IPF with diagnosed infections. However, accumulating evidence suggests that infections (both bacterial and viral) may influence disease outcomes either as exacerbating agents or initiators of disease. Support for a viral role in disease initiation comes from studies demonstrating the presence of herpesviral DNA and epithelial cell stress in the lungs of asymptomatic relatives at risk for developing familial IPF. In addition, the number of studies that can associate viral (especially herpesviral) signatures in the lung with the development of IPF is steadily growing, and activated leukocyte signatures in patients with IPF provide further support for infectious processes driving IPF progression. Animal modeling has been used to better understand how a gamma herpesvirus infection can modulate the pathogenesis of lung fibrosis and has demonstrated that preceding infections appear to reprogram lung epithelial cells during latency to produce profibrotic factors, making the lung more susceptible to subsequent fibrotic insult, whereas exacerbations of existing fibrosis, or infections in susceptible hosts, involve active viral replication and are influenced by antiviral therapy. In addition, there is new evidence that bacterial burden in the lungs of patients with IPF may predict a poor prognosis.",,"['Moore, Bethany B.', 'Moore, Thomas A.']",,,,
,PMC,Pathophysiological Consequences of Calcium-Conducting Viroporins,http://dx.doi.org/10.1146/annurev-virology-100114-054846,PMC6538290,,,"Eukaryotic cells have evolved a myriad of ion channels, transporters, and pumps to maintain and regulate transmembrane ion gradients. As intracellular parasites, viruses also have evolved ion channel proteins, called viroporins, which disrupt normal ionic homeostasis to promote viral replication and pathogenesis. The first viral ion channel (influenza M2 protein) was confirmed only 23 years ago, and since then studies on M2 and many other viroporins have shown they serve critical functions in virus entry, replication, morphogenesis, and immune evasion. As new candidate viroporins and viroporin-mediated functions are being discovered, we review the experimental criteria for viroporin identification and characterization to facilitate consistency within this field of research. Then we review recent studies on how the few Ca(2+)-conducting viroporins exploit host signaling pathways, including store-operated Ca(2+) entry, autophagy, and inflammasome activation. These viroporin-induced aberrant Ca(2+) signals cause pathophysiological changes resulting in diarrhea, vomiting, and proinflammatory diseases, making both the viroporin and host Ca(2+) signaling pathways potential therapeutic targets for antiviral drugs.",,"['Hyser, Joseph M.', 'Estes, Mary K.']",,,,
,PMC,Continuous and Discontinuous RNA Synthesis in Coronaviruses,http://dx.doi.org/10.1146/annurev-virology-100114-055218,PMC6025776,,,"Replication of the coronavirus genome requires continuous RNA synthesis, whereas transcription is a discontinuous process unique among RNA viruses. Transcription includes a template switch during the synthesis of subgenomic negative-strand RNAs to add a copy of the leader sequence. Coronavirus transcription is regulated by multiple factors, including the extent of base-pairing between transcription-regulating sequences of positive and negative polarity, viral and cell protein–RNA binding, and high-order RNA-RNA interactions. Coronavirus RNA synthesis is performed by a replication-transcription complex that includes viral and cell proteins that recognize cis-acting RNA elements mainly located in the highly structured 5′ and 3′ untranslated regions. In addition to many viral nonstructural proteins, the presence of cell nuclear proteins and the viral nucleocapsid protein increases virus amplification efficacy. Coronavirus RNA synthesis is connected with the formation of double-membrane vesicles and convoluted membranes. Coronaviruses encode proofreading machinery, unique in the RNA virus world, to ensure the maintenance of their large genome size.",,"['Sola, Isabel', 'Almazán, Fernando', 'Zúñiga, Sonia', 'Enjuanes, Luis']",,,,
,PMC,Comparative safety of vaccine adjuvants: a summary of current evidence and future needs,http://dx.doi.org/10.1007/s40264-015-0350-4,PMC4615573,,,"Improved use of highly pure antigens to improve vaccine safety has led to reduced vaccine immunogenicity and efficacy. This has led to the need to use adjuvants to improve vaccine immunogenicity. The ideal adjuvant should maximize vaccine immunogenicity without compromising tolerability or safety or posing undue risk. Unfortunately, adjuvant research has lagged behind other vaccine areas such as antigen discovery, with the consequence that only a very limited number of adjuvants based on aluminum salts, monophosphoryl lipid A and oil emulsions are currently approved for human use. Recent strategic initiatives to support adjuvant development by the National Institutes of Health should translate into greater adjuvant choices in the future. Mechanistic studies have been valuable in better understanding adjuvant action but mechanisms of adjuvant toxicity are less well understood. The inflammatory or danger-signal model of adjuvant action implies that increased vaccine reactogenicity is the inevitable price for improved immunogenicity. Hence, adjuvant reactogenicity may be avoidable only if it is possible to separate inflammation from adjuvant action. The biggest remaining challenge in the adjuvant field is to decipher the potential relationship between adjuvants and rare vaccine adverse reactions such as narcolepsy, macrophagic myofasciitis or Alzheimer’s disease. While existing adjuvants based on aluminum salts have a strong safety record, there is an ongoing need for new adjuvants and for more intensive research into adjuvants and their effects.",,"Petrovsky, Nikolai",,,,
,PMC,ABCB1 polymorphisms associated with osteonecrosis of the femeral head,,PMC4713659,,,"Aims: This case-control study was conducted to investigate the relation of ATP-binding cassette subfamily B member 1 (ABCB1) C1236T and C3435T polymorphisms and non-traumatic osteonecrosis of the femeral head (ONFH). Methods: We gathered 113 ONFH patients and 116 controls in the study. The polymorphisms of ABCB1 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. Odds ratio (OR) with 95% confidence interval (CI) were adopted to analyze the correlation between ABCB1 polymorphisms and ONFH. Results: In the study, we found that the frequency of C3435T TT genotype was much lower in case group, compared with that of controls (17.7% vs. 23.3%). Moreover, OR and 95% CI values indicated that C3435T TT genotype served as a protective factor for ONFH (OR=0.34, 95% CI=0.15-0.75). Meanwhile, the risk for the T allele carriers was much lower than C allele (OR=0.60, 95% CI=0.42-0.87). However, C1236T polymorphism showed no significant effects on the pathogenesis of ONFH. In the haplotype analysis, T-T haplotype appeared to be an inhibitor for ONFH (OR=0.45, 95% CI=0.23-0.87). Conclusions: Based on the results, ABCB1 polymorphisms were associated with the risk for ONFH.",,"['Zhang, Zongyu', 'Li, Yawei', 'Liu, Huaiying', 'Shi, Jinhui', 'Li, Xuefeng', 'Jiang, Weimin']",,,,
,PMC,The role of MBL2 gene polymorphism in sepsis incidence,,PMC4713640,,,"Aim: This case-control study was aimed to explore the role of mannose-binding lectin 2 (MBL2) gene rs1800450 polymorphism (codon 54 A/B, G230A) in the development of sepsis in Han Chinese. Methods: MBL2 rs1800450 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). MBL serum level was detected by enzyme-linked immunosorbent assay (ELISA). Associations between rs1800450 and sepsis susceptibility was detected by Chi-square test and represented by odds ratios (ORs) and 95% confidence intervals (CIs). Correlation of rs1800450 genotypes and MBL serum level was assessed using t test. Result: Variant A allele frequency was significantly observed in cases than that in controls, indicating a significant association with the susceptibility of sepsis (OR = 1.979, 95% CI = 1.200-3.262). GA genotype also relate to the onset of sepsis (OR = 2.090, 95% CI = 1.163-3.753). MBL serum concentrations were significantly different between case and control groups (P<0.001). Meanwhile, variant allele carriers had lower serum level compared with wild homozygous (P<0.001). Conclusion: Variant A allele in MBL2 gene rs1800450 polymorphism might increase the risk of sepsis via decrease the MBL serum level.",,"['Liu, Lei', 'Ning, Bo']",,,,
,PMC,Effect of Cage-Wash Temperature on the Removal of Infectious Agents from Caging and the Detection of Infectious Agents on the Filters of Animal Bedding-Disposal Cabinets by PCR Analysis,,PMC4671790,,,"Efficient, effective cage decontamination and the detection of infection are important to sustainable biosecurity within animal facilities. This study compared the efficacy of cage washing at 110 and 180 °F on preventing pathogen transmission. Soiled cages from mice infected with mouse parvovirus (MPV) and mouse hepatitis virus (MHV) were washed at 110 or 180 °F or were not washed. Sentinels from washed cages did not seroconvert to either virus, whereas sentinels in unwashed cages seroconverted to both agents. Soiled cages from mice harboring MPV, Helicobacter spp., Mycoplasma pulmonis, Syphacia obvelata, and Myocoptes musculinus were washed at 110 or 180 °F or were not washed. Sentinels from washed cages remained pathogen-free, whereas most sentinels in unwashed cages became infected with MPV and S. obvelata. Therefore washing at 110 or 180 °F is sufficient to decontaminate caging and prevent pathogen transmission. We then assessed whether PCR analysis of debris from the bedding disposal cabinet detected pathogens at the facility level. Samples were collected from the prefilter before and after the disposal of bedding from cages housing mice infected with both MPV and MHV. All samples collected before bedding disposal were negative for parvovirus and MHV, and all samples collected afterward were positive for these agents. Furthermore, all samples obtained from the prefilter before the disposal of bedding from multiply infected mice were pathogen-negative, and all those collected afterward were positive for parvovirus, M. pulmonis, S. obvelata, and Myocoptes musculinus. Therefore the debris on the prefilter of bedding-disposal cabinets is useful for pathogen screening.",,"['Compton, Susan R', 'Macy, James D']",,,,
,PMC,Translational readthrough-promoting drugs enhance pseudoknot-mediated suppression of the stop codon at the Moloney murine leukemia virus gag–pol junction,http://dx.doi.org/10.1099/jgv.0.000284,PMC5972331,,,"Translational readthrough-promoting drugs enhance the incorporation of amino acids at stop codons and can thus bypass premature termination during protein synthesis. The polymerase (Pol) proteins of Moloney murine leukemia virus (MoMLV) are synthesized as a large Gag–Pol fusion protein, formed by the readthrough of a stop codon at the end of the gag ORF. The downstream pol ORF lacks its own start codon, and Pol protein synthesis is wholly dependent on translation of the upstream gag gene and the readthrough event for expression. Here, we explored the effects of readthrough-promoting drugs – aminoglycoside antibiotics and the small molecule ataluren – on the efficiency of readthrough of the stop codon in the context of the MoMLV genome. We showed that these compounds increased readthrough of the stop codon at the MoMLV gag–pol junction in vivo above the already high basal level and that the resulting elevated gag–pol readthrough had deleterious effects on virus replication. We also showed that readthrough efficiency could be driven to even higher levels in vitro, and that the combination of the small molecules and the RNA structure at the MoMLV stop codon could achieve extremely high readthrough efficiencies.",,"['Green, Lisa', 'Goff, Stephen P.']",,,,
,PMC,An FcγRIIa Polymorphism with Decreased C-Reactive Protein Binding is Associated with Sepsis and Decreased Monocyte HLA-DR Expression in Trauma Patients,http://dx.doi.org/10.1097/TA.0000000000000837,PMC4621776,,,"INTRODUCTION: A dysregulated immune response leading to sepsis is the most frequent cause of late post-traumatic deaths. We have found a novel anti-inflammatory pathway that is initiated by the acute phase protein, C-reactive protein (CRP), interacting with Fcγ receptor (FcγR) on monocytes. This pathway is protective in animal models of endotoxin shock. We hypothesized that genetic polymorphisms in the FcγR might contribute to monocyte responses and susceptibility to infectious complications after severe trauma. METHODS: We conducted an observational study on a prospectively identified cohort of adult patients with convenience enrollment admitted after severe trauma. We enrolled 66 patients and collected blood samples at enrollment and again at 48 and 72 hrs. Patients were followed through their hospital stay and any septic events before 14 days were recorded. Cytokine and CRP levels were determined in the plasma from all three blood draws. Additionally, DNA was extracted from blood and analyzed for the 131 H/R FcγRIIa polymorphism that strongly affects the binding of IgG and CRP to this receptor. RESULTS: Elevated levels of IL-8, IL-6, IL-10 MCP-1 as well as CRP were associated with reduced time to post-traumatic sepsis in Cox regression analysis. Expression of monocyte HLA-DR below 45% on patient monocytes was also associated with sepsis (HR = 3.15, 95% CI 1.45-6.93). Genetic analysis found that individuals with the polymorphism of the FcγRIIa receptor that binds CRP poorly were also more likely to have decreased monocyte HLA-DR and post-traumatic sepsis. In vitro studies showed that CRP could attenuate monocyte deactivation in volunteers with the polymorphism of the FcγRIIa receptor that binds CRP. CONCLUSIONS: Our findings suggest that a common genetic variation in the FcγRIIa receptor may contribute to infectious susceptibility in trauma patients. In vitro experiments suggest that this association is related to the inability of CRP to bind to this FcγRIIa receptor variant. LEVEL OF EVIDENCE: Prognostic study, level III",,"['West, Sonlee D.', 'Ziegler, Anna', 'Brooks, Tamara', 'Krencicki, Michael', 'Myers, Orrin', 'Mold, Carolyn']",,,,
,PMC,Simultaneous Extraction of Viral and Bacterial Nucleic Acids for Molecular Diagnostic Applications,http://dx.doi.org/10.7171/jbt.15-2604-002,PMC4627512,,,"Molecular detection of microbial pathogens in clinical samples requires the application of efficient sample lysis protocols and subsequent extraction and isolation of their nucleic acids. Here, we describe a simple and time-efficient method for simultaneous extraction of genomic DNA from gram-positive and -negative bacteria, as well as RNA from viral agents present in a sample. This method compared well with existing bacterial- and viral-specialized extraction protocols, worked reliably on clinical samples, and was not pathogen specific. This method may be used to extract DNA and RNA concurrently from viral and bacterial pathogens present in a sample and effectively detect coinfections in routine clinical diagnostics.",,"['Kajiura, Lauren N.', 'Stewart, Scott D.', 'Dresios, John', 'Uyehara, Catherine F. T.']",,,,
,PMC,Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds,http://dx.doi.org/10.3791/53124,PMC4692676,,,"Cell-based systems are useful for discovering antiviral agents. Dissecting the viral life cycle, particularly the early entry stages, allows a mechanistic approach to identify and evaluate antiviral agents that target specific steps of the viral entry. In this report, the methods of examining viral inactivation, viral attachment, and viral entry/fusion as antiviral assays for such purposes are described, using hepatitis C virus as a model. These assays should be useful for discovering novel antagonists/inhibitors to early viral entry and help expand the scope of candidate antiviral agents for further drug development.",,"['Tai, Chen-Jei', 'Li, Chia-Lin', 'Tai, Cheng-Jeng', 'Wang, Chien-Kai', 'Lin, Liang-Tzung']",,,,
,PMC,Abstracts of the 29th Annual Symposium of The Protein Society,http://dx.doi.org/10.1002/pro.2823,PMC4632850,,,,,,,,,
,PMC,Negative immune checkpoints on T lymphocytes and their relevance to cancer immunotherapy,http://dx.doi.org/10.1016/j.molonc.2015.10.008,PMC5528732,,,"The term ‘inhibitory checkpoint’ refers to the broad spectrum of co‐receptors expressed by T cells that negatively regulate T cell activation thus playing a crucial role in maintaining peripheral self‐tolerance. Co‐inhibitory receptor ligands are highly expressed by a variety of malignancies allowing evasion of anti‐tumour immunity. Recent studies demonstrate that manipulation of these co‐inhibitory pathways can remove the immunological brakes that impede endogenous immune responses against tumours. Antibodies that block the interactions between co‐inhibitory receptors and their ligands have delivered very promising clinical responses, as has been shown by recent successful trials targeting the CTLA‐4 and PD‐1 pathways. In this review, we discuss the mechanisms of action and expression pattern of co‐inhibitory receptors on different T cells subsets, emphasising differences between CD4+ and CD8+ T cells. We also summarise recent clinical findings utilising immune checkpoint blockade.",,"['Śledzińska, Anna', 'Menger, Laurie', 'Bergerhoff, Katharina', 'Peggs, Karl S.', 'Quezada, Sergio A.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.02402-15,PMC4645640,,,,,,,,,
,PMC,lncRNA-mediated regulation of the interferon response,http://dx.doi.org/10.1016/j.virusres.2015.09.023,PMC4744491,,,"The interferon (IFN) response is a critical arm of the innate immune response and a major host defense mechanism against viral infections. Following microbial encounter, a series of signaling events lead to transcriptional activation of the IFN genes, which in turn leads to significant changes in the cellular transcriptome by altering the expression of hundreds of target genes. Emerging evidence suggest that long non-coding RNAs (lncRNAs) constitute a major subgroup of the IFN target genes, and further, that the IFN response is subject to regulation by a large number of host- and pathogen-derived lncRNAs. While the vast majority of lncRNAs with potential roles in the IFN response remain unstudied, analysis of a very small subset provides a glimpse of the regulatory impact of this class of RNAs on IFN response.",,"['Valadkhan, Saba', 'Gunawardane, Lalith S.']",,,,
,PMC,"Opposing tissue-specific roles of angiotensin in the pathogenesis of obesity, and implications for obesity-related hypertension",http://dx.doi.org/10.1152/ajpregu.00224.2015,PMC4698411,,,"Metabolic disease, specifically obesity, has now become the greatest challenge to improving cardiovascular health. The renin-angiotensin system (RAS) exists as both a circulating hormone system and as a local paracrine signaling mechanism within various tissues including the brain, kidney, and adipose, and this system is strongly implicated in cardiovascular health and disease. Growing evidence also implicates the RAS in the control of energy balance, supporting the concept that the RAS may be mechanistically involved in the pathogenesis of obesity and obesity hypertension. Here, we review the involvement of the RAS in the entire spectrum of whole organism energy balance mechanisms, including behaviors (food ingestion and spontaneous physical activity) and biological processes (digestive efficiency and both aerobic and nonaerobic resting metabolic rates). We hypothesize that opposing, tissue-specific effects of the RAS to modulate these various components of energy balance can explain the apparently paradoxical results reported by energy-balance studies that involve stimulating, versus disrupting, the RAS. We propose a model in which such opposing and tissue-specific effects of the RAS can explain the failure of simple, global RAS blockade to result in weight loss in humans, and hypothesize that obesity-mediated uncoupling of endogenous metabolic rate control mechanisms can explain the phenomenon of obesity-related hypertension.",,"['Littlejohn, Nicole K.', 'Grobe, Justin L.']",,,,
,PMC,"Baculovirus expression: old dog, new tricks",http://dx.doi.org/10.1080/21655979.2015.1104433,PMC4825837,,,"Since its inception more than 30 years ago, the baculovirus expression vector system (BEVS) has been used prolifically to produce heterologous proteins for research and development. In the cell, a cornerstone of biological activity are multiprotein complexes, catalyzing essential functions. BEVS has been uniquely successful to unlock such complex assemblies for high-resolution structural and functional analysis. Synthetic biology approaches have been implemented to optimize multigene assembly methods, accelerating upstream processes. Specialized baculoviral genomes are being created with functions tailored to enhance production of particular target protein classes. Here we comment on current and emerging developments in the field and their potential to accelerate protein complex research.",,"['Berger, Imre', 'Poterszman, Arnaud']",,,,
,PMC,Middle East Respiratory Syndrome Coronavirus Causes Multiple Organ Damage and Lethal Disease in Mice Transgenic for Human Dipeptidyl Peptidase 4,http://dx.doi.org/10.1093/infdis/jiv499,PMC4747621,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes life-threatening disease. Dipeptidyl peptidase 4 (DPP4) is the receptor for cell binding and entry. There is a need for small-animal models of MERS, but mice are not susceptible to MERS because murine dpp4 does not serve as a receptor. We developed transgenic mice expressing human DPP4 (hDPP4) under the control of the surfactant protein C promoter or cytokeratin 18 promoter that are susceptible to infection with MERS-CoV. Notably, mice expressing hDPP4 with the cytokeratin 18 promoter developed progressive, uniformly fatal disease following intranasal inoculation. High virus titers were present in lung and brain tissues 2 and 6 days after infection, respectively. MERS-CoV–infected lungs revealed mononuclear cell infiltration, alveolar edema, and microvascular thrombosis, with airways generally unaffected. Brain disease was observed, with the greatest involvement noted in the thalamus and brain stem. Animals immunized with a vaccine candidate were uniformly protected from lethal infection. These new mouse models of MERS-CoV should be useful for investigation of early disease mechanisms and therapeutic interventions.",,"['Li, Kun', 'Wohlford-Lenane, Christine', 'Perlman, Stanley', 'Zhao, Jincun', 'Jewell, Alexander K.', 'Reznikov, Leah R.', 'Gibson-Corley, Katherine N.', 'Meyerholz, David K.', 'McCray, Paul B.']",,,,
,PMC,Antibodies to an Interfering Epitope in Hepatitis C Virus E2 Can Mask Vaccine-Induced Neutralizing Activity,http://dx.doi.org/10.1002/hep.28108,PMC4681649,,,"Hepatitis C virus (HCV) neutralization occurring at the E2 region 412–426 (EP-I) could be enhanced when antibodies directed specifically to the E2 region 434–446 (EP-II) were removed from serum samples of persistently infected patients and vaccinated chimpanzees, a phenomenon of so-called antibody interference. Here we show that this type of interference can be observed in individuals after immunization with recombinant E1E2 proteins. One hundred and twelve blinded serum samples from a Phase I, placebo-controlled, dose escalation trial using recombinant HCV E1E2 with MF59C.1 adjuvant in healthy HCV-negative adults were tested in ELISA for binding reactivity to peptides representing the E2 regions 412–426 (EP-I) and 434–446 (EP-II). All samples were subsequently tested for neutralizing activity using HCVcc 1a(H77)/2a chimera, HCVpp H77 and HCVpp HCV-1 after treatment to remove EP-II-specific antibodies or mock treatment with a control peptide. Among the 112 serum samples we found 22 double positive (EP-I and EP-II), 6 EP-II positive only, 14 EP-I positive only and 70 double negative. Depleting EP-II antibodies from double positive serum samples increased ID(50) neutralizing antibody titers (up to 4.9-fold) in up to 72% of samples (p≤0.0005) contrasting with ID(50) neutralization titer increases in 2 of 70 double negative samples (2.9%) (p>0.5). In addition, EP-I-specific antibody levels in serum samples showed a significant correlation with ID(50) neutralization titers when EP-II antibodies were removed (p<0.0003). CONCLUSION: These data show that antibodies to the region 434–446 are induced during immunization of individuals with recombinant E1E2 proteins and that these antibodies can mask effective neutralizing activity from EP-I-specific antibodies. Elicitation of EP-II-specific antibodies with interfering capacity should be avoided in producing an effective cross-neutralizing vaccine aimed at the HCV envelope proteins.",,"['Kachko, Alla', 'Frey, Sharon E.', 'Sirota, Lev', 'Ray, Ranjit', 'Wells, Frances', 'Zubkova, Iryna', 'Zhang, Pei', 'Major, Marian E.']",,,,
,PMC,"Identification of a Bovine Enteric Calicivirus, Kırklareli Virus, Distantly Related to Neboviruses, in Calves with Enteritis in Turkey",http://dx.doi.org/10.1128/JCM.01736-15,PMC4609679,,,"A calicivirus was detected in neonatal calves with enteritis in Kırklareli, Thrace, Turkey. In the full-length genome, Kırklareli virus was related (48% nucleotide identity) to bovine enteric caliciviruses (Nebovirus genus). The virus was also detected in a herd in Ankara, Central Anatolia, but not in other Turkish prefectures.",,"['Alkan, Feray', 'Karayel, İlke', 'Catella, Cristiana', 'Bodnar, Livia', 'Lanave, Gianvito', 'Bányai, Krisztián', 'Di Martino, Barbara', 'Decaro, Nicola', 'Buonavoglia, Canio', 'Martella, Vito']",,,,
,PMC,Malaria vaccine based on Self-Assembling Protein Nanoparticles,http://dx.doi.org/10.1586/14760584.2015.1096781,PMC5019124,,,"Despite recent progress with GSK’s RTS’S malaria vaccine, there remains a desperate need for an efficient malaria vaccine. We have used a repetitive antigen display technology to display malaria specific B cell and T cell epitopes in an effort to design a vaccine against Plasmodium falciparum malaria. Our protein sequence when assembled into a nanoparticle induces strong, long-lived and protective immune responses against infection with the parasite. We are confident that the clinical trials with our most developed vaccine candidate will show good protection in a controlled human malaria infection trial.",,"['Burkhard, Peter', 'Lanar, David E']",,,,
,PMC,Clinical data analysis of 19 cases of community-acquired adenovirus pneumonia in immunocompetent adults,,PMC4694432,,,"The aim of this study was to investigate the characteristics of clinical manifestations, laboratory tests and imaging changes of community-acquired adenovirus pneumonia in immunocompetent adults. A retrospective study was performed on 19 adult community-acquired adenovirus pneumonia cases in Yantai, whereby the clinical data were collected and analyzed. Of 19 cases, 14 (73.68%) had fever and 17 (89.47%) had cough symptoms. Moreover, 14 cases (73.68%) had normal white blood cell counts, while 11 cases (57.89%) exhibited a reduction in lymphocyte proportion. Among the 19 cases, 17 cases exhibited lesions in a single lung, while 2 cases involved bilateral lungs. The lesions predominantly exhibited ground glass-like changes. The clinical manifestations of adult community-acquired adenovirus pneumonia patients with normal immune functions were mild, with such presenting symptoms as fever, cough, and sputum; most patients did not exhibit high levels of white blood cells or low lymphocyte counts, and the imaging features (ground glass-like effusion) were indicative of single-lung involvement.",,"['Yu, Hong-Xia', 'Zhao, Mao-Mao', 'Pu, Zeng-Hui', 'Wang, Yun-Qiang', 'Liu, Yan']",,,,
,PMC,The Potential Role of Social Media Platforms in Community Awareness of Antibiotic Use in the Gulf Cooperation Council States: Luxury or Necessity?,http://dx.doi.org/10.2196/jmir.3891,PMC4642378,26471079,CC BY,"The increasing emergence and spread of antimicrobial resistance (AMR) is a serious public health issue. Increasing the awareness of the general public about appropriate antibiotic use is a key factor for combating this issue. Several public media campaigns worldwide have been launched; however, such campaigns can be costly and the outcomes are variable and difficult to assess. Social media platforms, including Twitter, Facebook, and YouTube, are now frequently utilized to address health-related issues. In many geographical locations, such as the countries of the Gulf Cooperation Council (GCC) States (Saudi Arabia, United Arab Emirates, Kuwait, Oman, Qatar, and Bahrain), these platforms are becoming increasingly popular. The socioeconomic status of the GCC states and their reliable communication and networking infrastructure has allowed the penetration and scalability of these platforms in the region. This might explain why the Saudi Ministry of Health is using social media platforms alongside various other media platforms in a large-scale public awareness campaign to educate at-risk communities about the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV). This paper discusses the potential for using social media tools as cost-efficient and mass education platforms to raise awareness of appropriate antibiotic use in the general public and in the medical communities of the Arabian Peninsula.",2015 Oct 15,"['Zowawi, Hosam Mamoon', 'Abedalthagafi, Malak', 'Mar, Florie A', 'Almalki, Turki', 'Kutbi, Abdullah H', 'Harris-Brown, Tiffany', 'Harbarth, Stephan', 'Balkhy, Hanan H', 'Paterson, David L', 'Hasanain, Rihab Abdalazez']",J Med Internet Res,,,
,PMC,X-Ray structure and inhibition of the feline infectious peritonitis virus 3C-like protease: structural implications for drug design,http://dx.doi.org/10.1016/j.bmcl.2015.10.023,PMC5896745,,,"Feline infectious peritonitis (FIP) is a deadly disease that effects both domestic and wild cats and is caused by a mutation in feline coronavirus (FCoV) that allows the virus to replicate in macrophages. Currently, there are no treatments or vaccines available for the treatment of FIP even though it kills approximately 5% of cats in multi-cat households per year. In an effort to develop small molecule drugs targeting FIP for the treatment of cats, we screened a small set of designed peptidomimetic inhibitors for inhibition of FIPV-3CL(pro), identifying two compounds with low to sub-micromolar inhibition, compound 6 (IC(50)= 0.59 ± 0.06 nM) and compound 7 (IC(50)= 1.3 ± 0.1 μM). We determined the first X-ray crystal structure of FIPV-3CL(pro) in complex with the best inhibitor identified, compound 6, to a resolution of 2.10 Å to better understand the structural basis for inhibitor specificity. Our study provides important insights into the structural requirements for the inhibition of FIPV-3CL(pro) by peptidomimetic inhibitors and expands the current structural knowledge of coronaviral 3CL(pro) architecture.",,"['St. John, Sarah E.', 'Therkelsen, Matthew D.', 'Nyalapatla, Prasanth R.', 'Osswald, Heather L.', 'Ghosh, Arun K.', 'Mesecar, Andrew D.']",,,,
,PMC,Personal Protective Equipment - Protecting Healthcare Providers in an Ebola Outbreak,http://dx.doi.org/10.1016/j.clinthera.2015.07.007,PMC4661082,,,"PURPOSE: The current Ebola epidemic that has devastated West Africa has infected and killed more healthcare providers than any other outbreak in the history of this virus. An improved understanding of pathogen transmission and the institution of strategies to protect infection healthcare providers are needed in infectious disease outbreak. This review connects what is known about Ebola virus transmission with personal protective equipment designed to arrest nosocomial transmission. METHODS: Articles pertaining to filovirus transmission and personal protective equipment in filovirus outbreaks were reviewed and are presented. Additionally, studies evaluating PPE as well as donning and doffing strategies are also presented. FINDINGS: Personal Protective equipment is one step in a comprehensive infection prevention and control strategy that is required to protect healthcare providers. Given that the Ebola virus is primarily transmitted through direct contact of mucous membranes and cuts in the skin with infected patients and/or their bodily fluids, it is necessary to cover these potential portals of infection with PPE as part of a structured and instructed donning and doffing procedure. IMPLICATIONS: Current recommendations about PPE and the donning and doffing processes are based on anecdotal experience. However the use of non-human viruses can help provide evidence based guidelines on both PPE and processes.",,"['Fischer, William A.', 'Weber, David', 'Wohl, David A.']",,,,
,PMC,Flunarizine Prevents Hepatitis C Virus Membrane Fusion in a Genotype-dependent Manner by Targeting the Potential Fusion Peptide within E1,http://dx.doi.org/10.1002/hep.28111,PMC4688136,,,"To explore mechanisms of hepatitis C virus (HCV) replication we screened a compound library including licensed drugs. Flunarizine, a diphenylmethylpiperazine used to treat migraine, inhibited HCV cell entry in vitro and in vivo in a genotype-dependent fashion. Analysis of mosaic viruses between susceptible and resistant strains revealed that E1 and E2 glycoproteins confer susceptibility to flunarizine. Time of addition experiments and single particle tracking of HCV demonstrated that flunarizine specifically prevents membrane fusion. Related phenothiazines and pimozide also inhibited HCV infection and preferentially targeted HCV genotype 2 viruses. However, phenothiazines and pimozide exhibited improved genotype coverage including the difficult to treat genotype 3. Flunarizine-resistant HCV carried mutations within the alleged fusion peptide and displayed cross-resistance to these compounds, indicating that these drugs have a common mode of action. Conclusion: These observations reveal novel details about HCV membrane fusion. Moreover, flunarizine and related compounds represent first-in-class HCV fusion inhibitors that merit consideration for repurposing as cost-effective component of HCV combination therapies.",,"['Perin, Paula M.', 'Haid, Sibylle', 'Brown, Richard J. P.', 'Doerrbecker, Juliane', 'Schulze, Kai', 'Zeilinger, Carsten', 'von Schaewen, Markus', 'Heller, Brigitte', 'Vercauteren, Koen', 'Luxenburger, Eva', 'Baktash, Yasmine M.', 'Vondran, Florian W. R.', 'Speerstra, Sietkse', 'Awadh, Abdullah', 'Mukhtarov, Furkat', 'Schang, Luis M', 'Kirschning, Andreas', 'Müller, Rolf', 'Guzman, Carlos A.', 'Kaderali, Lars', 'Randall, Glenn', 'Meuleman, Philip', 'Ploss, Alexander', 'Pietschmann, Thomas']",,,,
,PMC,Diversification of β-Augmentation Interactions between CDI Toxin/ Immunity Proteins,http://dx.doi.org/10.1016/j.jmb.2015.09.020,PMC4658667,,,"Contact-dependent growth inhibition (CDI) is a widespread mechanism of inter-bacterial competition mediated by the CdiB/CdiA family of two-partner secretion proteins. CdiA effectors carry diverse C-terminal toxin domains (CdiA-CT), which are delivered into neighboring target cells to inhibit growth. CDI(+) bacteria also produce CdiI immunity proteins that bind specifically to cognate CdiA-CT toxins and protect the cell from auto-inhibition. Here, we compare the structures of homologous CdiA-CT/CdiI complexes from Escherichia coli EC869 and Yersinia pseudotuberculosis YPIII to explore the evolution of CDI toxin/immunity protein interactions. Both complexes share an unusual β-augmentation interaction, in which the toxin domain extends a β-hairpin into the immunity protein to complete a six-stranded anti-parallel sheet. However, the specific contacts differ substantially between the two complexes. The EC869 β-hairpin interacts mainly through direct H-bond and ion-pair interactions, whereas the YPIII β-hairpin pocket contains more hydrophobic contacts and a network of bridging water molecules. In accord with these differences, we find that each CdiI protein only protects target bacteria from its cognate CdiA-CT toxin. The compact β-hairpin binding pocket within the immunity protein represents a tractable system for the rationale design of small molecules to block CdiA-CT/ CdiI complex formation. We synthesized a macrocyclic peptide mimic of the β-hairpin from EC869 toxin and solved its structure in complex with cognate immunity protein. These latter studies suggest that small molecules could potentially be used to disrupt CDI toxin/immunity complexes.",,"['Morse, Robert P.', 'Willett, Julia L.E.', 'Johnson, Parker M.', 'Zheng, Mandy', 'Credali, Alfredo', 'Iniguez, Angelina', 'Nowick, James S.', 'Hayes, Christopher S.', 'Goulding, Celia W.']",,,,
,PMC,Monoclonal antibodies: Principles and applications of immmunodiagnosis and immunotherapy for hepatitis C virus,http://dx.doi.org/10.4254/wjh.v7.i22.2369,PMC4598607,,,"Hepatitis C virus (HCV) is a major health problem worldwide. Early detection of the infection will help better management of the infected cases. The monoclonal antibodies (mAb) of mice are predominantly used for the immunodiagnosis of several viral, bacterial, and parasitic antigens. Serological detection of HCV antigens and antibodies provide simple and rapid methods of detection but lack sensitivity specially in the window phase between the infection and antibody development. Human mAb are used in the immunotherapy of several blood malignancies, such as lymphoma and leukemia, as well as for autoimmune diseases. In this review article, we will discuss methods of mouse and human monoclonal antibody production. We will demonstrate the role of mouse mAb in the detection of HCV antigens as rapid and sensitive immunodiagnostic assays for the detection of HCV, which is a major health problem throughout the world, particularly in Egypt. We will discuss the value of HCV-neutralizing antibodies and their roles in the immunotherapy of HCV infections and in HCV vaccine development. We will also discuss the different mechanisms by which the virus escape the effect of neutralizing mAb. Finally, we will discuss available and new trends to produce antibodies, such as egg yolk-based antibodies (IgY), production in transgenic plants, and the synthetic antibody mimics approach.",,"['Tabll, Ashraf', 'Abbas, Aymn T', 'El-Kafrawy, Sherif', 'Wahid, Ahmed']",,,,
,PMC,Research Highlights,http://dx.doi.org/10.1038/mt.2015.160,PMC4817915,,,,,,,,,
,PMC,Dynamics of ADAM17-Mediated Shedding of ACE2 Applied to Pancreatic Islets of Male db/db Mice,http://dx.doi.org/10.1210/en.2015-1556,PMC4655210,,,"Angiotensin-converting enzyme 2 (ACE2) gene therapy aimed at counteracting pancreatic ACE2 depletion improves glucose regulation in two diabetic mouse models: db/db mice and angiotensin II-infused mice. A disintegrin and metalloproteinase 17 (ADAM17) can cause shedding of ACE2 from the cell membrane. The aim of our studies was to determine whether ADAM17 depletes ACE2 levels in pancreatic islets and β-cells. Dynamics of ADAM17-mediated ACE2 shedding were investigated in 832/13 insulinoma cells. Within a wide range of ACE2 expression levels, including the level observed in mouse pancreatic islets, overexpression of ADAM17 increases shed ACE2 and decreases cellular ACE2 levels. We provide a mathematical description of shed and cellular ACE2 activities as a function of the ADAM17 activity. The effect of ADAM17 on the cellular ACE2 content was relatively modest with an absolute control strength value less than 0.25 and approaching 0 at low ADAM17 activities. Although we found that ADAM17 and ACE2 are both expressed in pancreatic islets, the β-cell is not the major cell type expressing ACE2 in islets. During diabetes progression in 8-, 12-, and 15-week-old db/db mice, ACE2 mRNA and ACE2 activity levels in pancreatic islets were not decreased over time nor significantly decreased compared with nondiabetic db/m mice. Levels of ADAM17 mRNA and ADAM17 activity were also not significantly changed. Inhibiting basal ADAM17 activity in mouse islets failed to affect ACE2 levels. We conclude that whereas ADAM17 has the ability to shed ACE2, ADAM17 does not deplete ACE2 from pancreatic islets in diabetic db/db mice.",,"['Pedersen, Kim Brint', 'Chodavarapu, Harshita', 'Porretta, Constance', 'Robinson, Leonie K.', 'Lazartigues, Eric']",,,,
,PMC,Emerging tick-borne infections in mainland China: an increasing public health threat,http://dx.doi.org/10.1016/S1473-3099(15)00177-2,PMC4870934,,,"Since the beginning of the 1980s, 33 emerging tick-borne agents have been identified in mainland China, including eight species of spotted fever group rickettsiae, seven species in the family Anaplasmataceae, six genospecies in the complex Borrelia burgdorferi sensu lato, 11 species of Babesia, and the virus causing severe fever with thrombocytopenia syndrome. In this Review we have mapped the geographical distributions of human cases of infection. 15 of the 33 emerging tick-borne agents have been reported to cause human disease, and their clinical characteristics have been described. The non-specific clinical manifestations caused by tick-borne pathogens present a major diagnostic challenge and most physicians are unfamiliar with the many tick-borne diseases that present with non-specific symptoms in the early stages of the illness. Advances in and application of modern molecular techniques should help with identification of emerging tick-borne pathogens and improve laboratory diagnosis of human infections. We expect that more novel tick-borne infections in ticks and animals will be identified and additional emerging tick-borne diseases in human beings will be discovered.",,"['Fang, Li-Qun', 'Liu, Kun', 'Li, Xin-Lou', 'Liang, Song', 'Yang, Yang', 'Yao, Hong-Wu', 'Sun, Ruo-Xi', 'Sun, Ye', 'Chen, Wan-Jun', 'Zuo, Shu-Qing', 'Ma, Mai-Juan', 'Li, Hao', 'Jiang, Jia-Fu', 'Liu, Wei', 'Yang, X Frank', 'Gray, Gregory C', 'Krause, Peter J', 'Cao, Wu-Chun']",,,,
,PMC,Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus,http://dx.doi.org/10.1038/nrmicro3524,PMC5201123,,,"Ebola viruses and Marburg viruses, members of the filovirus family, are zoonotic pathogens that cause severe disease in people. The Ebola virus epidemic in West Africa, which was first recognized in early 2014, highlights the threat posed by these deadly viruses. Filovirus disease is characterized by uncontrolled virus replication and the activation of damaging host pathways. Underlying these phenomena is the potent suppression of host innate antiviral responses, particularly the type I interferon (IFN) response, which allows high levels of replication. Here we review the mechanisms deployed by filoviruses to block host innate immunity and discuss aspects of virus replication that promote disease.",,"['Messaoudi, Ilhem', 'Amarasinghe, Gaya K.', 'Basler, Christopher F.']",,,,
,PMC,Development of next-generation respiratory virus vaccines through targeted modifications to viral immunomodulatory genes,http://dx.doi.org/10.1586/14760584.2015.1095096,PMC4889331,,,"Vaccines represent one of the greatest contributions of the scientific community to global health. Yet, many pathogens remain either unchallenged or inadequately hindered by commercially available vaccines. Respiratory viruses pose distinct and difficult challenges due to their ability to rapidly spread, adapt, and modify the host immune response. Considerable research has been directed to understand the role of respiratory virus immunomodulatory proteins and how they influence the host immune response. We review here efforts to develop next-generation vaccines through targeting these key immunomodulatory genes in influenza virus, coronaviruses, respiratory syncytial virus, measles virus, and mumps virus.",,"['Stobart, Christopher C.', 'Moore, Martin L.']",,,,
,PMC,Severe respiratory illness associated with a nationwide outbreak of enterovirus D68 in the USA (2014): a descriptive epidemiological investigation,http://dx.doi.org/10.1016/S2213-2600(15)00335-5,PMC5693332,,,"BACKGROUND: Enterovirus D68 (EV-D68) has been infrequently reported historically, and is typically associated with isolated cases or small clusters of respiratory illness. Beginning in August, 2014, increases in severe respiratory illness associated with EV-D68 were reported across the USA. We aimed to describe the clinical, epidemiological, and laboratory features of this outbreak, and to better understand the role of EV-D68 in severe respiratory illness. METHODS: We collected regional syndromic surveillance data for epidemiological weeks 23 to 44, 2014, (June 1 to Nov 1, 2014) and hospital admissions data for epidemiological weeks 27 to 44, 2014, (June 29 to Nov 1, 2014) from three states: Missouri, Illinois and Colorado. Data were also collected for the same time period of 2013 and 2012. Respiratory specimens from severely ill patients nationwide, who were rhinovirus-positive or enterovirus-positive in hospital testing, were submitted between Aug 1, and Oct 31, 2014, and typed by molecular sequencing. We collected basic clinical and epidemiological characteristics of EV-D68 cases with a standard data collection form submitted with each specimen. We compared patients requiring intensive care with those who did not, and patients requiring ventilator support with those who did not. Mantel-Haenszel χ(2) tests were used to test for statistical significance. FINDINGS: Regional and hospital-level data from Missouri, Illinois, and Colorado showed increases in respiratory illness between August and September, 2014, compared with in 2013 and 2012. Nationwide, 699 (46%) of 1529 patients tested were confirmed as EV-D68. Among the 614 EV-D68-positive patients admitted to hospital, age ranged from 3 days to 92 years (median 5 years). Common symptoms included dyspnoea (n=513 [84%]), cough (n=500 [81%]), and wheezing (n=427 [70%]); 294 (48%) patients had fever. 338 [59%] of 574 were admitted to intensive care units, and 145 (28%) of 511 received ventilator support; 322 (52%) of 614 had a history of asthma or reactive airway disease; 200 (66%) of 304 patients with a history of asthma or reactive airway disease required intensive care compared with 138 (51%) of 270 with no history of asthma or reactive airway disease (p=0·0004). Similarly, 89 (32%) of 276 patients with a history of asthma or reactive airway disease required ventilator support compared with 56 (24%) of 235 patients with no history of asthma or reactive airway disease (p=0·039). INTERPRETATION: In 2014, EV-D68 caused widespread severe respiratory illness across the USA, disproportionately affecting those with asthma. This unexpected event underscores the need for robust surveillance of enterovirus types, enabling improved understanding of virus circulation and disease burden. FUNDING: None.",,"['Midgley, Claire M', 'Watson, John T', 'Nix, W Allan', 'Curns, Aaron T', 'Rogers, Shannon L', 'Brown, Betty A', 'Conover, Craig', 'Dominguez, Samuel R', 'Feikin, Daniel R', 'Gray, Samantha', 'Hassan, Ferdaus', 'Hoferka, Stacey', 'Jackson, Mary Anne', 'Johnson, Daniel', 'Leshem, Eyal', 'Miller, Lisa', 'Nichols, Janell Bezdek', 'Nyquist, Ann-Christine', 'Obringer, Emily', 'Patel, Ajanta', 'Patel, Megan', 'Rha, Brian', 'Schneider, Eileen', 'Schuster, Jennifer E', 'Selvarangan, Rangaraj', 'Seward, Jane F', 'Turabelidze, George', 'Oberste, M Steven', 'Pallansch, Mark A', 'Gerber, Susan I', None]",,,,
,PMC,Role of epithelial sodium channels in the regulation of lung fluid homeostasis,http://dx.doi.org/10.1152/ajplung.00319.2015,PMC4669342,,,"In utero, fetal lung epithelial cells actively secrete Cl(−) ions into the lung air spaces while Na(+) ions follow passively to maintain electroneutrality. This process, driven by an electrochemical gradient generated by the Na(+)-K(+)-ATPase, is responsible for the secretion of fetal fluid that is essential for normal lung development. Shortly before birth, a significant upregulation of amiloride-sensitive epithelial channels (ENaCs) on the apical side of the lung epithelial cells results in upregulation of active Na(+) transport. This process is critical for the reabsorption of fetal lung fluid and the establishment of optimum gas exchange. In the adult lung, active Na(+) reabsorption across distal lung epithelial cells limits the degree of alveolar edema in patients with acute lung injury and cardiogenic edema. Cl(−) ions are transported either paracellularly or transcellularly to preserve electroneutrality. An increase in Cl(−) secretion across the distal lung epithelium has been reported following an acute increase in left atrial pressure and may result in pulmonary edema. In contrast, airway epithelial cells secrete Cl(−) through apical cystic fibrosis transmembrane conductance regulator and Ca(2+)-activated Cl(−) channels and absorb Na(+). Thus the coordinated action of Cl(−) secretion and Na(+) absorption is essential for maintenance of the volume of epithelial lining fluid that, in turn, maximizes mucociliary clearance and facilitates clearance of bacteria and debris from the lungs. Any factor that interferes with Na(+) or Cl(−) transport or dramatically upregulates ENaC activity in airway epithelial cells has been associated with lung diseases such as cystic fibrosis or chronic obstructive lung disease. In this review we focus on the role of the ENaC, the mechanisms involved in ENaC regulation, and how ENaC dysregulation can lead to lung pathology.",,"['Matalon, Sadis', 'Bartoszewski, Rafal', 'Collawn, James F.']",,,,
,PMC,Sphingosine-1-Phosphate Receptor Antagonism Enhances Proliferation and Migration of Engrafted Neural Progenitor Cells in a Model of Viral-Induced Demyelination,http://dx.doi.org/10.1016/j.ajpath.2015.06.009,PMC4607760,,,"The oral drug FTY720 affects sphingosine-1-phosphate (S1P) signaling on targeted cells that bear the S1P receptors S1P1, S1P3, S1P4, and S1P5. We examined the effect of FTY720 treatment on the biology of mouse neural progenitor cells (NPCs) after transplantation in a viral model of demyelination. Intracerebral infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV) resulted in an acute encephalomyelitis, followed by demyelination similar in pathology to the human demyelinating disease, multiple sclerosis. We have previously reported that intraspinal transplantation of mouse NPCs into JHMV-infected animals resulted in selective colonization of demyelinated lesions, preferential differentiation into oligodendroglia accompanied by axonal preservation, and increased remyelination. Cultured NPCs expressed transcripts for S1P receptors S1P1, S1P2, S1P3, S1P4, and S1P5. FTY720 treatment of cultured NPCs resulted in increased mitogen-activated protein kinase phosphorylation and migration after exposure to the chemokine CXCL12. Administration of FTY720 to JHMV-infected mice resulted in enhanced migration and increased proliferation of transplanted NPCs after spinal cord engraftment. FTY720 treatment did not improve clinical disease, diminish neuroinflammation or the severity of demyelination, nor increase remyelination. These findings argue that FTY720 treatment selectively increases NPC proliferation and migration but does not either improve clinical outcome or enhance remyelination after transplantation into animals in which immune-mediated demyelination is initiated by the viral infection of the central nervous system.",,"['Blanc, Caroline A.', 'Grist, Jonathan J.', 'Rosen, Hugh', 'Sears-Kraxberger, Ilse', 'Steward, Oswald', 'Lane, Thomas E.']",,,,
,PMC,Effectiveness of Border Screening for Detecting Influenza in Arriving Airline Travelers,http://dx.doi.org/10.2105/AJPH.2012.300761r,PMC4561613,,,"Objectives. We measured symptom and influenza prevalence, and the effectiveness of symptom and temperature screening for identifying influenza, in arriving international airline travelers. Methods. This cross-sectional study collected data from travelers to Christchurch International Airport, New Zealand, in winter 2008, via a health questionnaire, temperature testing, and respiratory sampling. Results. Forms were returned by 15 976 (68%) travelers. Of these, 17% reported at least 1 influenza symptom, with runny or blocked nose (10%) and cough (8%) most common. Respiratory specimens were obtained from 3769 travelers. Estimated prevalence of influenza was 1.1% (4% among symptomatic, 0.2% among asymptomatic). The sensitivity of screening criteria ranged from 84% for “any symptom” to 3% for a fever of 37.8 °C or greater. The positive predictive value was low for all criteria. Conclusions. Border screening using self-reported symptoms and temperature testing has limitations for preventing pandemic influenza from entering a country. Using “any symptom” or cough would lead to many uninfected people being investigated, yet some infected people would remain undetected. If more specific criteria such as fever were used, most infected people would enter the country despite screening.",,"['Priest, Patricia C.', 'Jennings, Lance C.', 'Duncan, Alasdair R.', 'Brunton, Cheryl R.', 'Baker, Michael G.']",,,,
,PMC,Eficacia de la detección sistemática de la gripe en las fronteras en los viajeros que llegan por vía aérea*,http://dx.doi.org/10.2105/AJPH.2012.300761s,PMC4561608,,,"Objetivos. Se midieron los síntomas y la prevalencia de la gripe (también llamada influenza), así como la eficacia del mecanismo de detección sistemática basado en los síntomas y la temperatura para diagnosticar la gripe en viajeros internacionales que llegaban por vía aérea. Métodos. El presente estudio transversal recopiló datos de viajeros que llegaron al aeropuerto internacional de Christchurch (Nueva Zelandia) en el invierno del 2008 mediante un cuestionario de salud, medición de la temperatura y toma de muestras de las vías respiratorias. Resultados. De los viajeros, 15 976 (68%) entregaron los formularios completos. De ellos, 17% notificaron al menos un síntoma de gripe; los síntomas más comunes fueron rinorrea o congestión nasal (10%) y tos (8%). Se tomaron muestras de las vías respiratorias de 3 769 viajeros. La prevalencia estimada de la gripe fue de 1,1% (4% en las personas sintomáticas, 0,2% en las asintomáticas). La sensibilidad de los criterios de detección varió de 84% para “cualquier síntoma” a 3% para la fiebre de 37,8 °C o mayor. El valor predictivo positivo fue bajo para todos los criterios. Conclusiones. El método de detección sistemática en las fronteras mediante la autonotificación de síntomas y la toma de la temperatura presenta limitaciones para impedir que una gripe pandémica entre en un país. Basarse en criterios como “cualquier síntoma” o la tos haría que se investigara a varias personas no infectadas, mientras que algunas personas infectadas pasarían inadvertidas. Si se usaran criterios más específicos como la fiebre, la mayoría de las personas infectadas entrarían en el país a pesar del mecanismo de detección.",,"['Priest, Patricia C.', 'Jennings, Lance C.', 'Duncan, Alasdair R.', 'Brunton, Cheryl R.', 'Baker, Michael G.']",,,,
,PMC,Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol,http://dx.doi.org/10.1513/AnnalsATS.201503-172OT,PMC4627423,,,"Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant’s clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis.",,"['Moller, David R.', 'Koth, Laura L.', 'Maier, Lisa A.', 'Morris, Alison', 'Drake, Wonder', 'Rossman, Milton', 'Leader, Joseph K.', 'Collman, Ronald G.', 'Hamzeh, Nabeel', 'Sweiss, Nadera J.', 'Zhang, Yingze', 'O’Neal, Scott', 'Senior, Robert M.', 'Becich, Michael', 'Hochheiser, Harry S.', 'Kaminski, Naftali', 'Wisniewski, Stephen R.', 'Gibson, Kevin F.']",,,,
,PMC,Adoptive T cell therapy for the treatment of viral infections,http://dx.doi.org/10.3978/j.issn.2305-5839.2015.10.12,PMC4630547,,,,,"['Arasaratnam, Reuben J.', 'Leen, Ann M.']",,,,
,PMC,Acute BVDV-2 infection in beef calves delays humoral responses to a non-infectious antigen challenge,,PMC4572827,,,"Immunosuppressive effects of an intranasal challenge with non-cytopathic bovine viral diarrhea virus (BVDV) 2a (strain 1373) were assessed through acquired and innate immune system responses to ovalbumin (OVA). Concurrent BVDV infection was hypothesized to delay and reduce the humoral response to ovalbumin (administered on days 3 and 15 post-inoculation). Infected animals followed the expected clinical course. BVDV titers, and anti-BVDV antibodies confirmed the course of infection and were not affected by the administration of OVA. Both the T-helper (CD4(+)) and B-cell (CD20(+)) compartments were significantly (P < 0.05) reduced in infected animals, while the gamma-delta T-cell population (Workshop cluster 1+, WC1(+)) decreased slightly in numbers. Infection with BVDV delayed the increase in OVA IgG by approximately 3 d from day 12 through day 21 post-inoculation. Between days 25 and 37 post-inoculation following BVDV infection the IgM concentration in the BVDV− group decreased while the OVA IgM titer still was rising in the BVDV+ animals. Thus, active BVDV infection delays IgM and IgG responses to a novel, non-infectious antigen.",,"[None, 'McCorkell, Robert', 'Horsman, Shawn R.', 'Wynne-Edwards, Katherine', 'Muench, Greg', 'van Drunen Littel-van den Hurk, Sylvia', 'Waeckerlin, Regula', 'Eschbaumer, Michael', 'Dardari, Rkia', 'Chaiyakul, Mark', 'Gajda, Pawel', 'Czub, Markus', 'van der Meer, Frank']",,,,
,PMC,Postnatal Infections and Immunology Affecting Chronic Lung Disease of Prematurity,http://dx.doi.org/10.1016/j.clp.2015.08.002,PMC4660246,,,"Premature infants suffer significant respiratory morbidity during infancy with long-term negative consequences on health, quality of life, and health care costs. Enhanced susceptibility to a variety of infections and inflammation play a large role in early and prolonged lung disease following premature birth, though the mechanisms of susceptibility and immune dysregulation are active areas of research. This chapter will review aspects of host-pathogen interactions and immune responses that are altered by preterm birth and that impact chronic respiratory morbidity in these children.",,"Pryhuber, Gloria S.",,,,
,PMC,Cutaneous Epitheliotropic T-Cell Lymphoma in a Marsh Rice Rat (Oryzomys palustris),,PMC4617332,,,"Published reports of spontaneous neoplasia in marsh rice rats (Oryzomys palustris) are sparse. We report here a case of cutaneous epitheliotropic T-cell lymphoma in a 14-mo-old marsh rice rat that involved the ear pinnae, with dissemination to the liver and spleen. Histologically, the thickened ear pinnae showed diffuse infiltration of neoplastic lymphocytes into the epidermis, dermis, and adnexal skin structures, with Pautrier microaggregations present in the epidermis. In addition, neoplastic lymphocytes were observed infiltrating and disrupting the architecture of the liver and spleen. Neoplastic lymphocytes were strongly positive for the T-cell marker CD3 but were negative for the B-cell markers CD19 and CD20. These histologic and immunohistochemical features are consistent with an epitheliotropic T-cell lymphoma, as previously reported in other species, including humans. To our knowledge, this report represents the first published case of spontaneous cutaneous epitheliotropic T-cell lymphoma in a marsh rice rat.",,"['Taylor, Bryan F', 'Bekkevold, Christine M', 'Aguirre, J Ignacio', 'Andrutis, Karl', 'Reinhard, Mary K']",,,,
,PMC,Effectiveness of the Middle East respiratory syndrome-coronavirus protocol in enhancing the function of an Emergency Department in Qatar,http://dx.doi.org/10.1097/MEJ.0000000000000285,PMC5747930,,,"OBJECTIVE: This study aimed to investigate the effectiveness of a Middle East respiratory syndrome coronavirs (MERS-CoV) surveillance protocol in the Emergency Department (ED) at Hamad General Hospital. Effectiveness was measured by: (a) reduction in the number of patients admitted into the MERS-CoV tracking system; (b) identification of positive MERS-CoV cases; (c) containment of cross infectivity; and (d) increased efficiency in ED functioning. METHODS: A retrospective chart review was carried out of all ED patients suspected of MERS-CoV during the height of the epidemic (August to October 2013). An algorithm was created on the basis of international guidelines to screen and triage suspected MERS-CoV patients. Once identified, patients were isolated, had a chest roentgenogram [chest radiography (CXR)] taken, and a nasopharyngeal swab for PCR was sent with sputum samples for testing. Patients with normal CXR and mild respiratory symptoms were discharged with home isolation instructions until nasopharyngeal and sputum PCR results were available. Patients with fever and acute respiratory distress, with or without abnormal CXR, were treated in the hospital until tests proved negative for MERS-CoV. RESULTS: The protocol successfully reduced the number of patients who needed to be tested for MERS-CoV from 12 563 to 514, identified seven positive cases, and did not lead to apparent cross infectivity that resulted in serious illness or death. The protocol also increased the efficiency of ED and cut the turnaround time for nasopharyngeal swab and sputum results from 3 days to 1 day. CONCLUSION: A highly protocolized surveillance system limited the impact of MERS-CoV on ED functioning by identifying and prioritizing high-risk patients. The emergence of new infectious diseases requires constant monitoring of interventions to reduce the impact of epidemics on population health and health services.",,"['Varughese, Shinu', 'Read, Jennan G.', 'Al-khal, Abdul L.', 'Abo Saleh, Salem', 'El Deeb, Yasser', 'Cameron, Peter A.']",,,,
,PMC,A study on the role of noninvasive ventilation in mild-to-moderate acute respiratory distress syndrome,http://dx.doi.org/10.4103/0972-5229.167037,PMC4637959,26628824,CC BY-NC-SA,"AIM: There is sparse data on the role of noninvasive ventilation (NIV) in acute respiratory distress syndrome (ARDS) from India. Herein, we report our experience with the use of NIV in mild to moderate ARDS. MATERIALS AND METHODS: This was a prospective observational study involving consecutive subjects of ARDS treated with NIV using an oronasal mask. Patients were monitored clinically with serial arterial blood gas analysis. The success of NIV, duration of NIV use, Intensive Care Unit stay, hospital mortality, and improvement in clinical and blood gas parameters were assessed. The success of NIV was defined as prevention of endotracheal intubation. RESULTS: A total of 41 subjects (27 women, mean age: 30.9 years) were included in the study. Tropical infections followed by abdominal sepsis were the most common causes of ARDS. The use of NIV was successful in 18 (44%) subjects, while 23 subjects required intubation. The median time to intubation was 3 h. Overall, 19 (46.3%) deaths were encountered, all in those requiring invasive ventilation. The mean duration of ventilation was significantly higher in the intubated patients (7.1 vs. 2.6 days, P = 0.004). Univariate analysis revealed a lack of improvement in PaO(2)/FiO(2) at 1 h and high baseline Acute Physiology and Chronic Health Evaluation II (APACHE II) as predictors of NIV failure. CONCLUSIONS: Use of NIV in mild to moderate ARDS helped in avoiding intubation in about 44% of the subjects. A baseline APACHE II score of >17 and a PaO(2)/FiO(2) ratio <150 at 1 h predicts NIV failure.",2015 Oct,"['Sehgal, Inderpaul Singh', 'Chaudhuri, Soumik', 'Dhooria, Sahajal', 'Agarwal, Ritesh', 'Chaudhry, Dhruva']",Indian J Crit Care Med,,,
,PMC,Protecting Healthcare Personnel from Acquiring Ebola Virus Disease,http://dx.doi.org/10.1017/ice.2015.205,PMC5656048,,,,,"['Weber, David J.', 'Fischer, William A.', 'Wohl, David A.', 'Rutala, William A.']",,,,
,PMC,Porcine reproductive and respiratory syndrome virus 3C protease cleaves the mitochondrial antiviral signalling complex to antagonize IFN-β expression,http://dx.doi.org/10.1099/jgv.0.000257,PMC5410108,,,"Porcine reproductive and respiratory syndrome, a highly infectious disease caused by porcine reproductive and respiratory syndrome virus (PRRSV), has developed various strategies to evade the host innate immune response, including the suppression of type I IFN activation. The mitochondrial antiviral signalling protein (MAVS) is an important bridging adaptor of retinoic acid-inducible gene I/melanoma differentiation-associated protein 5 signalling pathways. Here, we demonstrated that the 3C-like protease (3CLSP) of PRRSV prevented the induction of IFN-β by cleaving MAVS in a proteasome- and caspase-independent manner. Moreover, this cleavage ability was dependent on the protease activity of 3CLSP. Mutations specifically disrupting the cysteine protease activity of 3CLSP eliminated MAVS cleavage and the inhibition of IFN induction. Subsequently, we determined that 3CLSP cleaved MAVS at Glu268. Remarkably, a MAVS point mutation at Glu268 rendered MAVS resistant to 3CLSP cleavage. These results reveal a novel PRRSV mechanism to escape host immunity by directly cleaving MAVS.",,"['Dong, Jianming', 'Xu, Shangen', 'Wang, Jing', 'Luo, Rui', 'Wang, Dang', 'Xiao, Shaobo', 'Fang, Liurong', 'Chen, Huanchun', 'Jiang, Yunbo']",,,,
,PMC,Ethnic variations in morbidity and mortality from lower respiratory tract infections: a retrospective cohort study,http://dx.doi.org/10.1177/0141076815588321,PMC4622271,,,"OBJECTIVE: There is evidence of substantial ethnic variations in asthma morbidity and the risk of hospitalisation, but the picture in relation to lower respiratory tract infections is unclear. We carried out an observational study to identify ethnic group differences for lower respiratory tract infections. DESIGN: A retrospective, cohort study. SETTING: Scotland. PARTICIPANTS: 4.65 million people on whom information was available from the 2001 census, followed from May 2001 to April 2010. MAIN OUTCOME MEASURES: Hospitalisations and deaths (any time following first hospitalisation) from lower respiratory tract infections, adjusted risk ratios and hazard ratios by ethnicity and sex were calculated. We multiplied ratios and confidence intervals by 100, so the reference Scottish White population’s risk ratio and hazard ratio was 100. RESULTS: Among men, adjusted risk ratios for lower respiratory tract infection hospitalisation were lower in Other White British (80, 95% confidence interval 73–86) and Chinese (69, 95% confidence interval 56–84) populations and higher in Pakistani groups (152, 95% confidence interval 136–169). In women, results were mostly similar to those in men (e.g. Chinese 68, 95% confidence interval 56–82), although higher adjusted risk ratios were found among women of the Other South Asians group (145, 95% confidence interval 120–175). Survival (adjusted hazard ratio) following lower respiratory tract infection for Pakistani men (54, 95% confidence interval 39–74) and women (31, 95% confidence interval 18–53) was better than the reference population. CONCLUSIONS: Substantial differences in the rates of lower respiratory tract infections amongst different ethnic groups in Scotland were found. Pakistani men and women had particularly high rates of lower respiratory tract infection hospitalisation. The reasons behind the high rates of lower respiratory tract infection in the Pakistani community are now required.",,"['Simpson, Colin R', 'Steiner, Markus FC', 'Cezard, Genevieve', 'Bansal, Narinder', 'Fischbacher, Colin', 'Douglas, Anne', 'Bhopal, Raj', 'Sheikh, Aziz']",,,,
,PMC,Dendritic cells: microbial clearance via autophagy and potential immunobiological consequences for periodontal disease,http://dx.doi.org/10.1111/prd.12096,PMC4530502,,,"Dendritic cells are potent antigen-capture and -presenting cells that play a key role in the initiation and regulation of the adaptive immune response. This process of immune homeostasis, as maintained by dendritic cells, is susceptible to dysregulation by certain pathogens during chronic infections. Such dysregulation may lead to disease perpetuation with potentially severe systemic consequences. Here we discuss in detail how intracellular pathogens exploit dendritic cells and evade degradation by altering or evading autophagy. This novel mechanism explains in part the chronic, persistent nature observed in several immuno-inflammatory diseases, including periodontal disease. Also, here we propose a hypothetical model on the plausible role of autophagy in the context of periodontal disease. Promotion of autophagy may open new therapeutic strategies in the search for a “cure” for periodontal disease in humans.",,"['El-Awady, Ahmed R.', 'Arce, Roger M.', 'Cutler, Christopher W.']",,,,
,PMC,From Individuals to Groups and Back: The Evolutionary Implications of Group Phenotypic Composition,http://dx.doi.org/10.1016/j.tree.2015.07.005,PMC4594155,26411618,CC BY,"There is increasing interest in understanding the processes that maintain phenotypic variation in groups, populations, or communities. Recent studies have investigated how the phenotypic composition of groups or aggregations (e.g., its average phenotype or phenotypic variance) affects ecological and social processes, and how multi-level selection can drive phenotypic covariance among interacting individuals. However, we argue that these questions are rarely studied together. We present a unified framework to address this gap, and discuss how group phenotypic composition (GPC) can impact on processes ranging from individual fitness to population demography. By emphasising the breadth of topics affected, we hope to motivate more integrated empirical studies of the ecological and evolutionary implications of GPC.",2015 Oct,"['Farine, Damien R.', 'Montiglio, Pierre-Olivier', 'Spiegel, Orr']",Trends Ecol Evol,,,
,PMC,Revisiting the concept of CNS immune privilege,http://dx.doi.org/10.1016/j.it.2015.08.006,PMC4593064,,,"Whereas the study of the interactions between the immune system and the central nervous system (CNS) has often focused on pathological conditions, the importance of neuroimmune communication in CNS homeostasis and function has become clear over that last two decades. Here we discuss the progression of our understanding of the interaction between the peripheral immune system and the CNS. We examine the notion of immune privilege of the CNS in light of both earlier findings and recent studies revealing a functional meningeal lymphatic system that drains cerebrospinal fluid (CSF) to the deep cervical lymph nodes, and consider the implications of a revised perspective on the immune privilege of the CNS on the etiology and pathology of different neurological disorders.",,"['Louveau, Antoine', 'Harris, Tajie H.', 'Kipnis, Jonathan']",,,,
,PMC,Immune surveillance of the CNS following infection and injury,http://dx.doi.org/10.1016/j.it.2015.08.002,PMC4592776,,,"The central nervous system (CNS) contains a sophisticated neural network that must be constantly surveyed in order to detect and mitigate a diverse array of challenges. The innate and adaptive immune systems actively participate in this surveillance, which is critical for the maintenance of CNS homeostasis and can facilitate the resolution of infections, degeneration, and tissue damage. Infections and sterile injuries represent two common challenges imposed on the CNS that require a prompt immune response. While the inducers of these two challenges differ in origin, the resultant responses orchestrated by the CNS share some overlapping features. Here, we review how the CNS immunologically discriminates between pathogens and sterile injuries, mobilizes an immune reaction, and, ultimately, regulates local and peripherally-derived immune cells to provide a supportive milieu for tissue repair.",,"['Russo, Matthew', 'McGavern, Dorian B.']",,,,
,PMC,Stealing the Keys to the Kitchen: Viral Manipulation of the Host Cell Metabolic Network,http://dx.doi.org/10.1016/j.tim.2015.08.007,PMC4679435,,,"Host cells possess the metabolic assets required for viral infection. Recent studies indicate that control of the host’s metabolic resources is a core host-pathogen interaction. Viruses have evolved mechanisms to usurp the host’s metabolic resources, funneling them towards the production of virion components as well as the organization of specialized compartments for replication, maturation, and dissemination. Consequently, hosts have developed a variety of metabolic countermeasures to sense and resist these viral changes. The complex interplay between virus and host over metabolic control has only just begun to be deconvoluted. However, it is clear that virally induced metabolic reprogramming can substantially impact infectious outcomes, highlighting the promise of targeting these processes for antiviral therapeutic development.",,"['Goodwin, Christopher M.', 'Xu, Shihao', 'Munger, Joshua']",,,,
,PMC,Fluorescence polarization-based nucleic acid testing for rapid and cost-effective diagnosis of infectious disease,http://dx.doi.org/10.1002/chem.201502934,PMC4816641,,,"A new nucleic acid detection method was developed for a rapid and cost-effective diagnosis of infectious disease. This approach relies on the three unique elements: (i) detection probes that regulate DNA polymerase activity in response to the complementary target DNA; (ii) universal reporters conjugated with a single fluorophore; and (iii) fluorescence polarization (FP) detection. As a proof-of-concept, the assay was used to detect and sub-type Salmonella bacteria with sensitivities down to a single bacterium in relatively short periods of time.",,"['Park, Ki Soo', 'Charles, Richelle C.', 'Ryan, Edward T.', 'Weissleder, Ralph', 'Lee, Hakho']",,,,
,PMC,Ultrastructural Characterization of Turnip Mosaic Virus-Induced Cellular Rearrangements Reveals Membrane-Bound Viral Particles Accumulating in Vacuoles,http://dx.doi.org/10.1128/JVI.02138-15,PMC4665257,,,"Positive-strand RNA [(+) RNA] viruses remodel cellular membranes to facilitate virus replication and assembly. In the case of turnip mosaic virus (TuMV), the viral membrane protein 6K(2) plays an essential role in endomembrane alterations. Although 6K(2)-induced membrane dynamics have been widely studied by confocal microscopy, the ultrastructure of this remodeling has not been extensively examined. In this study, we investigated the formation of TuMV-induced membrane changes by chemical fixation and high-pressure freezing/freeze substitution (HPF/FS) for transmission electron microscopy at different times of infection. We observed the formation of convoluted membranes connected to rough endoplasmic reticulum (rER) early in the infection process, followed by the production of single-membrane vesicle-like (SMVL) structures at the midstage of infection. Both SMVL and double-membrane vesicle-like structures with electron-dense cores, as well as electron-dense bodies, were found late in the infection process. Immunogold labeling results showed that the vesicle-like structures were 6K(2) tagged and suggested that only the SMVL structures were viral RNA replication sites. Electron tomography (ET) was used to regenerate a three-dimensional model of these vesicle-like structures, which showed that they were, in fact, tubules. Late in infection, we observed filamentous particle bundles associated with electron-dense bodies, which suggests that these are sites for viral particle assembly. In addition, TuMV particles were observed to accumulate in the central vacuole as membrane-associated linear arrays. Our work thus unravels the sequential appearance of distinct TuMV-induced membrane structures for viral RNA replication, viral particle assembly, and accumulation. IMPORTANCE Positive-strand RNA viruses remodel cellular membranes for different stages of the infection process, such as protein translation and processing, viral RNA synthesis, particle assembly, and virus transmission. The ultrastructure of turnip mosaic virus (TuMV)-induced membrane remodeling was investigated over several days of infection. The first change that was observed involved endoplasmic reticulum-connected convoluted membrane accumulation. This was followed by the formation of single-membrane tubules, which were shown to be viral RNA replication sites. Later in the infection process, double-membrane tubular structures were observed and were associated with viral particle bundles. In addition, TuMV particles were observed to accumulate in the central vacuole as membrane-associated linear arrays. This work thus unravels the sequential appearance of distinct TuMV-induced membrane structures for viral RNA replication, viral particle assembly, and accumulation.",,"['Wan, Juan', 'Basu, Kaustuv', 'Mui, Jeannie', 'Vali, Hojatollah', 'Zheng, Huanquan', 'Laliberté, Jean-François']",,,,
,PMC,MDA5 Is Critical to Host Defense during Infection with Murine Coronavirus,http://dx.doi.org/10.1128/JVI.01470-15,PMC4665247,,,"Infection with the murine coronavirus mouse hepatitis virus (MHV) activates the pattern recognition receptors melanoma differentiation-associated gene 5 (MDA5) and Toll-like receptor 7 (TLR7) to induce transcription of type I interferon. Type I interferon is crucial for control of viral replication and spread in the natural host, but the specific contributions of MDA5 signaling to this pathway as well as to pathogenesis and subsequent immune responses are largely unknown. In this study, we use MHV infection of the liver as a model to demonstrate that MDA5 signaling is critically important for controlling MHV-induced pathology and regulation of the immune response. Mice deficient in MDA5 expression (MDA5(−/−) mice) experienced more severe disease following MHV infection, with reduced survival, increased spread of virus to additional sites of infection, and more extensive liver damage than did wild-type mice. Although type I interferon transcription decreased in MDA5(−/−) mice, the interferon-stimulated gene response remained intact. Cytokine production by innate and adaptive immune cells was largely intact in MDA5(−/−) mice, but perforin induction by natural killer cells and levels of interferon gamma, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in serum were elevated. These data suggest that MDA5 signaling reduces the severity of MHV-induced disease, at least in part by reducing the intensity of the proinflammatory cytokine response. IMPORTANCE Multicellular organisms employ a wide range of sensors to detect viruses and other pathogens. One such sensor, MDA5, detects viral RNA and triggers induction of type I interferons, chemical messengers that induce inflammation and help regulate the immune responses. In this study, we sought to determine the role of MDA5 during infection with mouse hepatitis virus, a murine coronavirus used to model viral hepatitis as well as other human diseases. We found that mice lacking the MDA5 sensor were more susceptible to infection than were mice with MDA5 and experienced decreased survival. Viral replication in the liver was similar in mice with and without MDA5, but liver damage was increased in MDA5(−/−) mice, suggesting that the immune response is causing the damage. Production of several proinflammatory cytokines was elevated in MDA5(−/−) mice, suggesting that MDA5 may be responsible for keeping pathological inflammatory responses in check.",,"['Zalinger, Zachary B.', 'Elliott, Ruth', 'Rose, Kristine M.', 'Weiss, Susan R.']",,,,
,PMC,Induction and Antagonism of Antiviral Responses in Respiratory Syncytial Virus-Infected Pediatric Airway Epithelium,http://dx.doi.org/10.1128/JVI.02119-15,PMC4665230,,,"Airway epithelium is the primary target of many respiratory viruses. However, virus induction and antagonism of host responses by human airway epithelium remains poorly understood. To address this, we developed a model of respiratory syncytial virus (RSV) infection based on well-differentiated pediatric primary bronchial epithelial cell cultures (WD-PBECs) that mimics hallmarks of RSV disease in infants. RSV is the most important respiratory viral pathogen in young infants worldwide. We found that RSV induces a potent antiviral state in WD-PBECs that was mediated in part by secreted factors, including interferon lambda 1 (IFN-λ1)/interleukin-29 (IL-29). In contrast, type I IFNs were not detected following RSV infection of WD-PBECs. IFN responses in RSV-infected WD-PBECs reflected those in lower airway samples from RSV-hospitalized infants. In view of the prominence of IL-29, we determined whether recombinant IL-29 treatment of WD-PBECs before or after infection abrogated RSV replication. Interestingly, IL-29 demonstrated prophylactic, but not therapeutic, potential against RSV. The absence of therapeutic potential reflected effective RSV antagonism of IFN-mediated antiviral responses in infected cells. Our data are consistent with RSV nonstructural proteins 1 and/or 2 perturbing the Jak-STAT signaling pathway, with concomitant reduced expression of antiviral effector molecules, such as MxA/B. Antagonism of Jak-STAT signaling was restricted to RSV-infected cells in WD-PBEC cultures. Importantly, our study provides the rationale to further explore IL-29 as a novel RSV prophylactic. IMPORTANCE Most respiratory viruses target airway epithelium for infection and replication, which is central to causing disease. However, for most human viruses we have a poor understanding of their interactions with human airway epithelium. Respiratory syncytial virus (RSV) is the most important viral pathogen of young infants. To help understand RSV interactions with pediatric airway epithelium, we previously developed three-dimensional primary cell cultures from infant bronchial epithelium that reproduce several hallmarks of RSV infection in infants, indicating that they represent authentic surrogates of RSV infection in infants. We found that RSV induced a potent antiviral state in these cultures and that a type III interferon, interleukin IL-29 (IL-29), was involved. Indeed, our data suggest that IL-29 has potential to prevent RSV disease. However, we also demonstrated that RSV efficiently circumvents this antiviral immune response and identified mechanisms by which this may occur. Our study provides new insights into RSV interaction with pediatric airway epithelium.",,"['Villenave, Rémi', 'Broadbent, Lindsay', 'Douglas, Isobel', 'Lyons, Jeremy D.', 'Coyle, Peter V.', 'Teng, Michael N.', 'Tripp, Ralph A.', 'Heaney, Liam G.', 'Shields, Michael D.', 'Power, Ultan F.']",,,,
,PMC,Aerosol Delivery of siRNA to the Lungs. Part 1: Rationale for Gene Delivery Systems,http://dx.doi.org/10.14356/kona.2016014,PMC4829385,,,"This article reviews the pulmonary route of administration, aerosol delivery devices, characterization of pulmonary drug delivery systems, and discusses the rationale for inhaled delivery of siRNA. Diseases with known protein malfunctions may be mitigated through the use of siRNA therapeutics. The inhalation route of administration provides local delivery of siRNA therapeutics for the treatment of various pulmonary diseases, however barriers to pulmonary delivery and intracellular delivery of siRNA exists. siRNA loaded nanocarriers can be used to overcome the barriers associated with the pulmonary route, such as anatomical barriers, mucociliary clearance, and alveolar macrophage clearance. Apart from naked siRNA aerosol delivery, previously studied siRNA carrier systems comprise of lipidic, polymeric, peptide, or inorganic origin. Such siRNA delivery systems formulated as aerosols can be successfully delivered via an inhaler or nebulizer to the pulmonary region. Preclinical animal investigations of inhaled siRNA therapeutics rely on intratracheal and intranasal siRNA and siRNA nanocarrier delivery. Aerosolized siRNA delivery systems may be characterized using in vitro techniques, such as dissolution test, inertial cascade impaction, delivered dose uniformity assay, laser diffraction, and laser Doppler velocimetry. The ex vivo techniques used to characterize pulmonary administered formulations include the isolated perfused lung model. In vivo techniques like gamma scintigraphy, 3D SPECT, PET, MRI, fluorescence imaging and pharmacokinetic/pharmacodynamics analysis may be used for evaluation of aerosolized siRNA delivery systems. The use of inhalable siRNA delivery systems encounters barriers to their delivery, however overcoming the barriers while formulating a safe and effective delivery system will offer unique advances to the field of inhaled medicine.",,"['Youngren-Ortiz, Susanne R.', 'Gandhi, Nishant S.', 'España-Serrano, Laura', 'Chougule, Mahavir B.']",,,,
,PMC,TRAF3: a novel tumor suppressor gene in macrophages,http://dx.doi.org/10.14800/macrophage.1009,PMC4673676,,,"Tumor necrosis factor receptor-associated factor 3 (TRAF3), a member of the TRAF family of cytoplasmic adaptor proteins with E3 ligase activity, is ubiquitously expressed in various cell types of the immune system. It is shared for signaling by a variety of adaptive and innate immune receptors as well as cytokine receptors. Previous studies examining conditional TRAF3-deficient mouse models that have the Traf3 gene specifically deleted in B lymphocytes or T lymphocytes have revealed the diverse and critical in vivo functions of TRAF3 in adaptive immunity. Although in vitro evidence points to a pivotal and indispensable role for TRAF3 in type I interferon production induced by pattern recognition receptors in macrophages and dendritic cells, the in vivo functions of TRAF3 in the innate immune system had long remained unclear. Three laboratories have recently addressed this gap in knowledge by investigating myeloid cell-specific TRAF3-deficient (genotype: TRAF3(flox/flox)LysM(+/Cre)) mice. The new evidence together demonstrates that specific ablation of TRAF3 in myeloid cells leads to inflammatory diseases, altered progression of diabetes, and spontaneous development of different types of tumors and infections in mice. These new findings indicate that TRAF3 acts as an anti-inflammatory factor and is required for optimal innate immunity in myeloid cells. Strikingly, the new evidence also identifies TRAF3 as a novel tumor suppressor gene in macrophages and other myeloid cells. In this review, we discuss and summarize the new findings and current knowledge about the multi-faceted regulatory roles and complex signaling mechanisms of myeloid cell TRAF3 in inflammation, innate immunity, and tumor development.",,"['Lalani, Almin I.', 'Luo, Chang', 'Han, Yeming', 'Xie, Ping']",,,,
,PMC,Lessons from Ebola: improving infectious disease surveillance to inform outbreak management,http://dx.doi.org/10.1126/scitranslmed.aab0191,PMC5819730,,,"The current Ebola virus disease outbreak in West Africa has revealed serious shortcomings in national and international capacity to detect, monitor, and respond to infectious disease outbreaks as they occur. Recent advances in diagnostics, risk mapping, mathematical modelling, pathogen genome sequencing, phylogenetics, and phylogeography have the potential to improve substantially the quantity and quality of information available to guide the public health response to outbreaks of all kinds.",,"['Woolhouse, Mark E.J.', 'Rambaut, Andrew', 'Kellam, Paul']",,,,
,PMC,Buried treasure: evolutionary perspectives on microbial iron piracy,http://dx.doi.org/10.1016/j.tig.2015.09.001,PMC4639441,,,"Host-pathogen interactions provide valuable systems for the study of evolutionary genetics and natural selection. The sequestration of essential iron has emerged as a critical innate defense system termed nutritional immunity, leading pathogens to evolve mechanisms of `iron piracy' to scavenge this metal from host proteins. This battle for iron carries numerous consequences not only for host-pathogen evolution, but also microbial community interactions. Here we highlight recent and potential future areas of investigation on the evolutionary implications of microbial iron piracy in relation to molecular arms races, host range, competition, and virulence. Applying evolutionary genetic approaches to the study of microbial iron acquisition could also provide new inroads for understanding and combating infectious disease.",,"['Barber, Matthew F.', 'Elde, Nels C.']",,,,
,PMC,Middle East respiratory syndrome: current status and future prospects for vaccine development,http://dx.doi.org/10.1517/14712598.2015.1092518,PMC4636333,,,"The outbreaks of Middle East respiratory syndrome (MERS) previously in Middle East and recently in South Korea have raised serious concerns world-wide, reinforcing the importance of developing effective and safe vaccines against MERS-coronavirus (MERS-CoV). A number of vaccine candidates have been developed on the basis of viral vectors, recombinant proteins, DNAs, nanoparticles, and recombinant MERS-CoV, and some of them have shown efficacy in laboratory animals. However, the paucity of financial support has made it difficult to transfer effective candidates from the preclinical stage to clinical trials. Here, we summarize currently available MERS vaccine candidates and illustrate strategies for future development, with the aim of provoking government agencies and Big Pharma to invest more funds for developing efficacious and safe MERS vaccines.",,"['Du, Lanying', 'Jiang, Shibo']",,,,
,PMC,Differences in the seasonality of MERS-CoV and influenza in the Middle East,http://dx.doi.org/10.1016/j.ijid.2015.09.012,PMC4666761,,,,,"['He, Daihai', 'Chiu, Alice P.Y.', 'Lin, Qianying', 'Cowling, Benjamin J.']",,,,
,PMC,Global biogeography of human infectious diseases,http://dx.doi.org/10.1073/pnas.1507442112,PMC4611664,,,"The distributions of most infectious agents causing disease in humans are poorly resolved or unknown. However, poorly known and unknown agents contribute to the global burden of disease and will underlie many future disease risks. Existing patterns of infectious disease co-occurrence could thus play a critical role in resolving or anticipating current and future disease threats. We analyzed the global occurrence patterns of 187 human infectious diseases across 225 countries and seven epidemiological classes (human-specific, zoonotic, vector-borne, non–vector-borne, bacterial, viral, and parasitic) to show that human infectious diseases exhibit distinct spatial grouping patterns at a global scale. We demonstrate, using outbreaks of Ebola virus as a test case, that this spatial structuring provides an untapped source of prior information that could be used to tighten the focus of a range of health-related research and management activities at early stages or in data-poor settings, including disease surveillance, outbreak responses, or optimizing pathogen discovery. In examining the correlates of these spatial patterns, among a range of geographic, epidemiological, environmental, and social factors, mammalian biodiversity was the strongest predictor of infectious disease co-occurrence overall and for six of the seven disease classes examined, giving rise to a striking congruence between global pathogeographic and “Wallacean” zoogeographic patterns. This clear biogeographic signal suggests that infectious disease assemblages remain fundamentally constrained in their distributions by ecological barriers to dispersal or establishment, despite the homogenizing forces of globalization. Pathogeography thus provides an overarching context in which other factors promoting infectious disease emergence and spread are set.",,"['Murray, Kris A.', 'Preston, Nicholas', 'Allen, Toph', 'Zambrana-Torrelio, Carlos', 'Hosseini, Parviez R.', 'Daszak, Peter']",,,,
,PMC,Estimating the Distribution of the Incubation Periods of Human Avian Influenza A(H7N9) Virus Infections,http://dx.doi.org/10.1093/aje/kwv115,PMC4597801,,,"A novel avian influenza virus, influenza A(H7N9), emerged in China in early 2013 and caused severe disease in humans, with infections occurring most frequently after recent exposure to live poultry. The distribution of A(H7N9) incubation periods is of interest to epidemiologists and public health officials, but estimation of the distribution is complicated by interval censoring of exposures. Imputation of the midpoint of intervals was used in some early studies, resulting in estimated mean incubation times of approximately 5 days. In this study, we estimated the incubation period distribution of human influenza A(H7N9) infections using exposure data available for 229 patients with laboratory-confirmed A(H7N9) infection from mainland China. A nonparametric model (Turnbull) and several parametric models accounting for the interval censoring in some exposures were fitted to the data. For the best-fitting parametric model (Weibull), the mean incubation period was 3.4 days (95% confidence interval: 3.0, 3.7) and the variance was 2.9 days; results were very similar for the nonparametric Turnbull estimate. Under the Weibull model, the 95th percentile of the incubation period distribution was 6.5 days (95% confidence interval: 5.9, 7.1). The midpoint approximation for interval-censored exposures led to overestimation of the mean incubation period. Public health observation of potentially exposed persons for 7 days after exposure would be appropriate.",,"['Virlogeux, Victor', 'Li, Ming', 'Tsang, Tim K.', 'Feng, Luzhao', 'Fang, Vicky J.', 'Jiang, Hui', 'Wu, Peng', 'Zheng, Jiandong', 'Lau, Eric H. Y.', 'Cao, Yu', 'Qin, Ying', 'Liao, Qiaohong', 'Yu, Hongjie', 'Cowling, Benjamin J.']",,,,
,PMC,Respiratory nanoparticle-based vaccines and challenges associated with animal models and translation,http://dx.doi.org/10.1016/j.jconrel.2015.09.047,PMC4760633,,,"Vaccine development has had a huge impact on human health. However, there is a significant need to develop efficacious vaccines for several existing as well as emerging respiratory infectious diseases. Several challenges need to be overcome to develop efficacious vaccines with translational potential. This review focuses on two aspects to overcome some barriers – 1) the development of nanoparticle-based vaccines, and 2) the choice of suitable animal models for respiratory infectious diseases that will allow for translation. Nanoparticle-based vaccines, including subunit vaccines involving synthetic and/or natural polymeric adjuvants and carriers, as well as those based on virus-like particles offer several key advantages to help overcome the barriers to effective vaccine development. These include the ability to deliver combinations of antigens, target the vaccine formulation to specific immune cells, enable cross-protection against divergent strains, act as adjuvants or immunomodulators, allow for sustained release of antigen, enable single dose delivery, and potentially obviate the cold chain. While mouse models have provided several important insights into the mechanisms of infectious diseases, they are often a limiting step in translation of new vaccines to the clinic. An overview of different animal models involved in vaccine research for respiratory infections, with advantages and disadvantages of each model, are discussed. Taken together, advances in nanotechnology, combined with the right animal models for evaluating vaccine efficacy, has the potential to revolutionize vaccine development for respiratory infections.",,"['Renukaradhya, Gourapura J.', 'Narasimhan, Balaji', 'Mallapragada, Surya K.']",,,,
,PMC,Genetic Dissection of the Host Tropism of Human-Tropic Pathogens,http://dx.doi.org/10.1146/annurev-genet-112414-054823,PMC5075990,,,"Infectious diseases are the second leading cause of death worldwide. Although the host multitropism of some pathogens has rendered their manipulation possible in animal models, the human-restricted tropism of numerous viruses, bacteria, fungi, and parasites has seriously hampered our understanding of these pathogens. Hence, uncovering the genetic basis underlying the narrow tropism of such pathogens is critical for understanding their mechanisms of infection and pathogenesis. Moreover, such genetic dissection is essential for the generation of permissive animal models that can serve as critical tools for the development of therapeutics or vaccines against challenging human pathogens. In this review, we describe different experimental approaches utilized to uncover the genetic foundation regulating pathogen host tropism as well as their relevance for studying the tropism of several important human pathogens. Finally, we discuss the current and future uses of this knowledge for generating genetically modified animal models permissive for these pathogens.",,"['Douam, Florian', 'Gaska, Jenna M.', 'Winer, Benjamin Y.', 'Ding, Qiang', 'von Schaewen, Markus', 'Ploss, Alexander']",,,,
,PMC,"Advax™, a novel microcrystalline polysaccharide particle engineered from delta inulin, provides robust adjuvant potency together with tolerability and safety",http://dx.doi.org/10.1016/j.vaccine.2015.09.030,PMC4639457,,,"There is an ongoing need for new adjuvants to facilitate development of vaccines against HIV, tuberculosis, malaria and cancer, amongst many others. Unfortunately, the most potent adjuvants are often associated with toxicity and safety issues. Inulin, a plant-derived polysaccharide, has no immunological activity in its native soluble form but when crystallised into stable microparticles (delta inulin) acquires potent adjuvant activity. Delta inulin has been shown to enhance humoral and cellular immune responses against a broad range of co-administered viral, bacterial, parasitic and toxin antigens. Inulin normally crystallises as large heterogeneous particles with a broad size distribution and variable solubility temperatures. To ensure reproducible delta inulin particles with a consistent size distribution and temperature of solubility, a current Good Manufacturing Practice (cGMP) process was designed to produce Advax™ adjuvant. In its cGMP form, Advax™ adjuvant has proved successful in human trials of vaccines against seasonal and pandemic influenza, hepatitis B and insect sting anaphylaxis, enhancing antibody and T-cell responses while at the same time being safe and well tolerated. Advax™ adjuvant thereby represents a novel human adjuvant with positive effects on both humoral and cellular immunity. This review describes the discovery and development of Advax™ adjuvant and research into its unique mechanism of action.",,"['Petrovsky, Nikolai', 'Cooper, Peter D.']",,,,
,PMC,"Clinical significance of dynamic monitoring of blood lactic acid, oxygenation index and C-reactive protein levels in patients with severe pneumonia",http://dx.doi.org/10.3892/etm.2015.2770,PMC4665687,,,"The aim of the present study was to analyze the clinical significance of the dynamic monitoring of blood lactic acid levels, the oxygenation index and C-reactive protein (CRP) levels in patients with severe pneumonia. The clinical data of 34 cases with severe pneumonia were collected. According to the clinical outcome, the patients were divided into a survival group (n=26) and a fatality group (n=8). Various factors, including the blood lactic acid level, oxygenation index, CRP level and acute physiology and chronic health evaluation II (APACHE II) score, were retrospectively analyzed in order to investigate whether these values had clinical significance for the prognosis of the patients. No statistically significant differences with regard to age, gender, initial concentrations of blood lactic acid and CRP, and APACHE II scores were observed between the two groups at admission to the Intensive Care Unit. However, the blood lactic acid levels were found to decrease to a normal level within 12–24 h after treatment in the survival group, while the levels were maintained at a higher concentration in the fatality group, even at 72 h after treatment (P<0.05). Furthermore, the oxygenation index in the survival group was significantly higher when compared with that in the fatality group. The oxygenation index was maintained at a normal level in the survival group, while the oxygenation index levels were below normal and continued to decline in the fatality group. A positive correlation was observed between the blood lactic acid level and the APACHE II scores (r=0.656, P<0.05). Therefore, the present study demonstrated that dynamic monitoring of blood lactic acid, oxygenation index and CRP levels in patients with severe pneumonia can be used to evaluate the therapeutic efficiency, in addition to serving as a prognosis indicator, for patients with severe pneumonia.",,"['LIU, WEI', 'PENG, LIPING', 'HUA, SHUCHENG']",,,,
,PMC,Acute viral respiratory infection rapidly induces a CD8(+) T cell exhaustion-like phenotype,http://dx.doi.org/10.4049/jimmunol.1403004,PMC4733528,,,"Acute viral infections typically generate functional effector CD8(+) T cells (T(CD8)) that aid in pathogen clearance. However, during acute viral lower respiratory infection (LRI), lung T(CD8) are functionally impaired and do not optimally control viral replication. T cells also become unresponsive to antigen during chronic infections and cancer via signaling by inhibitory receptors like programmed cell death-1 (PD-1). PD-1 also contributes to T(CD8) impairment during viral LRI, but how it regulates T(CD8) impairment and the connection between this state and T cell exhaustion during chronic infections is unknown. Here we show that PD-1 operates in a cell-intrinsic manner to impair lung T(CD8). In light of this, we compared global gene expression profiles of impaired epitope-specific lung T(CD8) to functional spleen T(CD8) in the same human metapneumovirus (HMPV)-infected mice. These two populations differentially regulate hundreds of genes, including the upregulation of numerous inhibitory receptors by lung T(CD8). We then compared the gene expression of T(CD8) during HMPV infection to those in acute or chronic LCMV infection. We find that the immunophenotype of lung T(CD8) more closely resembles T cell exhaustion late into chronic infection than functional effector T cells arising early in acute infection. Finally, we demonstrate that trafficking to the infected lung alone is insufficient for T(CD8) impairment or inhibitory receptor upregulation, but that viral antigen-induced TCR signaling is also required. Our results indicate that viral antigen in infected lungs rapidly induces an exhaustion-like state in lung T(CD8), characterized by progressive functional impairment and upregulation of numerous inhibitory receptors.",,"['Erickson, John J.', 'Lu, Pengcheng', 'Wen, Sherry', 'Hastings, Andrew K.', 'Gilchuk, Pavlo', 'Joyce, Sebastian', 'Shyr, Yu', 'Williams, John V.']",,,,
,PMC,A Synthetic Porcine Reproductive and Respiratory Syndrome Virus Strain Confers Unprecedented Levels of Heterologous Protection,http://dx.doi.org/10.1128/JVI.01657-15,PMC4645332,,,"Current vaccines do not provide sufficient levels of protection against divergent porcine reproductive and respiratory syndrome virus (PRRSV) strains circulating in the field, mainly due to the substantial variation of the viral genome. We describe here a novel approach to generate a PRRSV vaccine candidate that could confer unprecedented levels of heterologous protection against divergent PRRSV isolates. By using a set of 59 nonredundant, full-genome sequences of type 2 PRRSVs, a consensus genome (designated PRRSV-CON) was generated by aligning these 59 PRRSV full-genome sequences, followed by selecting the most common nucleotide found at each position of the alignment. Next, the synthetic PRRSV-CON strain was generated through the use of reverse genetics. PRRSV-CON replicates as efficiently as our prototype PRRSV strain FL12, both in vitro and in vivo. Importantly, when inoculated into pigs, PRRSV-CON confers significantly broader levels of heterologous protection than does wild-type PRRSV. Collectively, our data demonstrate that PRRSV-CON can serve as an excellent candidate for the development of a broadly protective PRRSV vaccine. IMPORTANCE The extraordinary genetic variation of RNA viruses poses a monumental challenge for the development of broadly protective vaccines against these viruses. To minimize the genetic dissimilarity between vaccine immunogens and contemporary circulating viruses, computational strategies have been developed for the generation of artificial immunogen sequences (so-called “centralized” sequences) that have equal genetic distances to the circulating viruses. Thus far, the generation of centralized vaccine immunogens has been carried out at the level of individual viral proteins. We expand this concept to PRRSV, a highly variable RNA virus, by creating a synthetic PRRSV strain based on a centralized PRRSV genome sequence. This study provides the first example of centralizing the whole genome of an RNA virus to improve vaccine coverage. This concept may be significant for the development of vaccines against genetically variable viruses that require active viral replication in order to achieve complete immune protection.",,"['Vu, Hiep L. X.', 'Ma, Fangrui', 'Laegreid, William W.', 'Pattnaik, Asit K.', 'Steffen, David', 'Doster, Alan R.', 'Osorio, Fernando A.']",,,,
,PMC,Infectious Bronchitis Coronavirus Inhibits STAT1 Signaling and Requires Accessory Proteins for Resistance to Type I Interferon Activity,http://dx.doi.org/10.1128/JVI.01057-15,PMC4645315,,,"The innate immune response is the first line of defense against viruses, and type I interferon (IFN) is a critical component of this response. Similar to other viruses, the gammacoronavirus infectious bronchitis virus (IBV) has evolved under evolutionary pressure to evade and counteract the IFN response to enable its survival. Previously, we reported that IBV induces a delayed activation of the IFN response. In the present work, we describe the resistance of IBV to IFN and the potential role of accessory proteins herein. We show that IBV is fairly resistant to the antiviral state induced by IFN and identify that viral accessory protein 3a is involved in resistance to IFN, as its absence renders IBV less resistant to IFN treatment. In addition to this, we found that independently of its accessory proteins, IBV inhibits IFN-mediated phosphorylation and translocation of STAT1. In summary, we show that IBV uses multiple strategies to counteract the IFN response. IMPORTANCE In the present study, we show that infectious bronchitis virus (IBV) is resistant to IFN treatment and identify a role for accessory protein 3a in the resistance against the type I IFN response. We also demonstrate that, in a time-dependent manner, IBV effectively interferes with IFN signaling and that its accessory proteins are dispensable for this activity. This study demonstrates that the gammacoronavirus IBV, similar to its mammalian counterparts, has evolved multiple strategies to efficiently counteract the IFN response of its avian host, and it identifies accessory protein 3a as multifaceted antagonist of the avian IFN system.",,"['Kint, Joeri', 'Dickhout, Annemiek', 'Kutter, Jasmin', 'Maier, Helena J.', 'Britton, Paul', 'Koumans, Joseph', 'Pijlman, Gorben P.', 'Fros, Jelke J.', 'Wiegertjes, Geert F.', 'Forlenza, Maria']",,,,
,PMC,Early Vertebrate Evolution of the Host Restriction Factor Tetherin,http://dx.doi.org/10.1128/JVI.02149-15,PMC4645306,,,"Tetherin is an interferon-inducible restriction factor targeting a broad range of enveloped viruses. Its antiviral activity depends on an unusual topology comprising an N-terminal transmembrane domain (TMD) followed by an extracellular coiled-coil region and a C-terminal glycosylphosphatidylinositol (GPI) anchor. One of the two membrane anchors is inserted into assembling virions, while the other remains in the plasma membrane of the infected cell. Thus, tetherin entraps budding viruses by physically bridging viral and cellular membranes. Although tetherin restricts the release of a large variety of diverse human and animal viruses, only mammalian orthologs have been described to date. Here, we examined the evolutionary origin of this protein and demonstrate that tetherin orthologs are also found in fish, reptiles, and birds. Notably, alligator tetherin efficiently blocks the release of retroviral particles. Thus, tetherin emerged early during vertebrate evolution and acquired its antiviral activity before the mammal/reptile divergence. Although there is only limited sequence homology, all orthologs share the typical topology. Two unrelated proteins of the slime mold Dictyostelium discoideum also adopt a tetherin-like configuration with an N-terminal TMD and a C-terminal GPI anchor. However, these proteins showed no evidence for convergent evolution and failed to inhibit virion release. In summary, our findings demonstrate that tetherin emerged at least 450 million years ago and is more widespread than previously anticipated. The early evolution of antiviral activity together with the high topology conservation but low sequence homology suggests that restriction of virus release is the primary function of tetherin. IMPORTANCE The continuous arms race with viruses has driven the evolution of a variety of cell-intrinsic immunity factors that inhibit different steps of the viral replication cycle. One of these restriction factors, tetherin, inhibits the release of newly formed progeny virions from infected cells. Although tetherin targets a broad range of enveloped viruses, including retro-, filo-, herpes-, and arenaviruses, the evolutionary origin of this restriction factor and its antiviral activity remained obscure. Here, we examined diverse vertebrate genomes for genes encoding cellular proteins that share with tetherin the highly unusual combination of an N-terminal transmembrane domain and a C-terminal glycosylphosphatidylinositol anchor. We show that tetherin orthologs are found in fish, reptiles, and birds and demonstrate that alligator tetherin efficiently inhibits the release of retroviral particles. Our findings identify tetherin as an evolutionarily ancient restriction factor and provide new important insights into the continuous arms race between viruses and their hosts.",,"['Heusinger, Elena', 'Kluge, Silvia F.', 'Kirchhoff, Frank', 'Sauter, Daniel']",,,,
,PMC,Rotavirus Controls Activation of the 2′-5′-Oligoadenylate Synthetase/RNase L Pathway Using at Least Two Distinct Mechanisms,http://dx.doi.org/10.1128/JVI.01874-15,PMC4645303,,,"The innate immune response is the first line of defense of the host cell against a viral infection. In turn, viruses have evolved a wide variety of strategies to hide from, and to directly antagonize, the host innate immune pathways. One of these pathways is the 2′-5′-oligoadenylate synthetase (OAS)/RNase L pathway. OAS is activated by double-stranded RNA (dsRNA) to produce 2′-5′ oligoadenylates, which are the activators of RNase L; this enzyme degrades viral and cellular RNAs, restricting viral infection. It has been recently found that the carboxy-terminal domain (CTD) of rotavirus VP3 has a 2′-5′-phosphodiesterase (PDE) activity that is able to functionally substitute for the PDE activity of the mouse hepatitis virus ns2 protein. This particular phosphodiesterase cleaves the 2′-5′-phosphodiester bond of the oligoadenylates, antagonizing the OAS/RNase L pathway. However, whether this activity of VP3 is relevant during the replication cycle of rotavirus is not known. Here, we demonstrate that after rotavirus infection the OAS/RNase L complex becomes activated; however, the virus is able to control its activity using at least two distinct mechanisms. A virus-cell interaction that occurs during or before rotavirus endocytosis triggers a signal that prevents the early activation of RNase L, while later on the control is taken by the newly synthesized VP3. Cosilencing the expression of VP3 and RNase L in infected cells yields viral infectious particles at levels similar to those obtained in control infected cells, where no genes were silenced, suggesting that the capping activity of VP3 is not essential for the formation of infectious viral particles. IMPORTANCE Rotaviruses represent an important cause of severe gastroenteritis in the young of many animal species, including humans. In this work, we have found that the OAS/RNase L pathway is activated during rotavirus infection, but the virus uses two different strategies to prevent the deleterious effects of this innate immune response of the cell. Early during virus entry, the initial interactions of the viral particle with the cell result in the inhibition of RNase L activity during the first hours of the infection. Later on, once viral proteins are synthesized, the phosphodiesterase activity of VP3 degrades the cellular 2′-5′-oligoadenylates, which are potent activators of RNase L, preventing its activation. This work demonstrates that the OAS/RNase L pathway plays an important role during infection and that the phosphodiesterase activity of VP3 is relevant during the replication cycle of the virus.",,"['Sánchez-Tacuba, Liliana', 'Rojas, Margarito', 'Arias, Carlos F.', 'López, Susana']",,,,
,PMC,A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein,http://dx.doi.org/10.1038/cr.2015.113,PMC4650419,,,"The newly-emerging Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans. Despite global efforts, the potential for an associated pandemic in the future cannot be excluded. The development of effective counter-measures is urgent. MERS-CoV-specific anti-viral drugs or vaccines are not yet available. Using the spike receptor-binding domain of MERS-CoV (MERS-RBD) to immunize mice, we identified two neutralizing monoclonal antibodies (mAbs) 4C2 and 2E6. Both mAbs potently bind to MERS-RBD and block virus entry in vitro with high efficacy. We further investigated their mechanisms of neutralization by crystallizing the complex between the Fab fragments and the RBD, and solved the structure of the 4C2 Fab/MERS-RBD complex. The structure showed that 4C2 recognizes an epitope that partially overlaps the receptor-binding footprint in MERS-RBD, thereby interfering with the virus/receptor interactions by both steric hindrance and interface-residue competition. 2E6 also blocks receptor binding, and competes with 4C2 for binding to MERS-RBD. Based on the structure, we further humanized 4C2 by preserving only the paratope residues and substituting the remaining amino acids with the counterparts from human immunoglobulins. The humanized 4C2 (4C2h) antibody sustained similar neutralizing activity and biochemical characteristics to the parental mouse antibody. Finally, we showed that 4C2h can significantly abate the virus titers in lungs of Ad5-hCD26-transduced mice infected with MERS-CoV, therefore representing a promising agent for prophylaxis and therapy in clinical settings.",,"['Li, Yan', 'Wan, Yuhua', 'Liu, Peipei', 'Zhao, Jincun', 'Lu, Guangwen', 'Qi, Jianxun', 'Wang, Qihui', 'Lu, Xuancheng', 'Wu, Ying', 'Liu, Wenjun', 'Zhang, Buchang', 'Yuen, Kwok-Yung', 'Perlman, Stanley', 'Gao, George F', 'Yan, Jinghua']",,,,
,PMC,Feeder use predicts both acquisition and transmission of a contagious pathogen in a North American songbird,http://dx.doi.org/10.1098/rspb.2015.1429,PMC4614752,,,"Individual heterogeneity can influence the dynamics of infectious diseases in wildlife and humans alike. Thus, recent work has sought to identify behavioural characteristics that contribute disproportionately to individual variation in pathogen acquisition (super-receiving) or transmission (super-spreading). However, it remains unknown whether the same behaviours enhance both acquisition and transmission, a scenario likely to result in explosive epidemics. Here, we examined this possibility in an ecologically relevant host–pathogen system: house finches and their bacterial pathogen, Mycoplasma gallisepticum, which causes severe conjunctivitis. We examined behaviours likely to influence disease acquisition (feeder use, aggression, social network affiliations) in an observational field study, finding that the time an individual spends on bird feeders best predicted the risk of conjunctivitis. To test whether this behaviour also influences the likelihood of transmitting M. gallisepticum, we experimentally inoculated individuals based on feeding behaviour and tracked epidemics within captive flocks. As predicted, transmission was fastest when birds that spent the most time on feeders initiated the epidemic. Our results suggest that the same behaviour underlies both pathogen acquisition and transmission in this system and potentially others. Identifying individuals that exhibit such behaviours is critical for disease management.",,"['Adelman, James S.', 'Moyers, Sahnzi C.', 'Farine, Damien R.', 'Hawley, Dana M.']",,,,
,PMC,Local corticosterone production and angiotensin-I converting enzyme shedding in a mouse model of intestinal inflammation,http://dx.doi.org/10.3748/wjg.v21.i35.10072,PMC4572788,,,"AIM: To investigate local corticosterone production and angiotensin-I converting enzyme (ACE) protein expression and their interaction in healthy and inflamed intestine. METHODS: Acute intestinal inflammation was induced to six weeks old male Balb/c mice by administration of either 3% or 5% dextran sodium sulfate (DSS) in drinking water for 7 d (n = 12 in each group). Healthy controls (n = 12) were given tap water. Corticosterone production and ACE protein shedding were measured from ex vivo incubates of the small and large intestine using EIA and ELISA, respectively. Morphological changes of the intestinal wall were assessed in hematoxylin-eosin stained tissue preparations of jejunum and distal colon. Effects of angiotensin II, captopril and metyrapone on corticosterone production was assessed by incubating pieces of small intestine of healthy mice in the presence of 0.1, 1 or 10 μmol/L angiotensin II, 1, 10 or 100 μmol/L captopril or 1, 10 or 100 μmol/L metyrapone solutions and measuring corticosterone released to the incubation buffer after 90 min (n = 5 in each group). RESULTS: Both concentrations of DSS induced inflammation and morphological changes in large intestines but not in small intestines. Changes were observed as distortions of the crypt structure, mucosal erosion, immune cell infiltration to the mucosa and submucosal edema. Ex vivo corticosterone production (2.9 ± 1.0 ng/mL vs 2.0 ± 0.8 ng/mL, P = 0.034) and ACE shedding (269.2 ± 97.1 ng/mL vs 175.7 ± 52.2 ng/mL, P = 0.016) were increased in small intestines in 3% DSS group compared to the controls. In large intestine, corticosterone production was increased compared to the controls in both 3% DSS (229 ± 81 pg/mL vs 158 ± 30 pg/mL, P = 0.017) and 5% DSS groups (366 ± 163 pg/mL vs 158 ± 30 pg/mL, P = 0.002). Large intestine ACE shedding was increased in 5% DSS group (41.5 ± 9.0 ng/mL vs 20.9 ± 5.2 ng/mL, P = 0.034). Angiotensin II treatment augmented corticosterone production in small intestine at concentration of 10 μmol/L (0.97 ± 0.21 ng/mg protein vs 0.40 ± 0.09 ng/mg protein, P = 0.036). CONCLUSION: Intestinal ACE shedding is increased by DSS-induced intestinal inflammation and parallels local corticosterone production. ACE product angiotensin II stimulates corticosterone formation in healthy intestine.",,"['Salmenkari, Hanne', 'Issakainen, Tomi', 'Vapaatalo, Heikki', 'Korpela, Riitta']",,,,
,PMC,The etiologic role of infectious antigens in sarcoidosis pathogenesis,http://dx.doi.org/10.1016/j.ccm.2015.08.001,PMC4660257,,,"Sarcoidosis is a granulomatous disease of unknown etiology, characterized by a Th1 immunophenotype, most commonly involving the lung, skin, lymph node and eyes. Molecular and immunologic studies continue to strengthen the association of sarcoidosis with infectious antigens, particularly those derived from Propionibacterium and Mycobacterium species. Independent studies report the presence of microbial nucleic acids and proteins within sarcoidosis specimens. Complementary immunologic studies also support the role of infectious agents in sarcoidosis pathogenesis. Th-1 immune responses directed against mycobacterial virulence factors have been detected within sarcoidosis diagnostic bronchoalveolar lavage (BAL). Th1 and Th17 immune responses against propionibacteria have also been reported. More recently, case reports and clinical trials from Japanese, European and American investigators have emerged regarding the efficacy of antimicrobials against Propionibacterium and Mycobacterium species on pulmonary and cutaneous sarcoidosis. While these clinical investigations are not conclusive, they support increasing efforts to identify novel therapeutics, such as antimicrobials, that will impact the observed increase in sarcoidosis morbidity and mortality.",,"['Celada, Lindsay J.', 'Hawkins, Charlene', 'Drake, Wonder P.']",,,,
,PMC,Influenza D Virus Infection in Mississippi Beef Cattle,http://dx.doi.org/10.1016/j.virol.2015.08.030,PMC4710178,,,"A new member of the Orthomyxoviridae family, influenza D virus (IDV), was first reported in swine in the Midwest region of the United States. This study aims to extend our knowledge on the IDV epidemiology and to determine the impact of bovine production systems on virus spread. A total of 15 isolates were recovered from surveillance of bovine herds in Mississippi, and two genetic clades of viruses co-circulated in the same herd. Serologic assessment from neonatal beef cattle showed 94% seropositive, and presumed maternal antibody levels were substantially lower in animals over six months of age. Active IDV transmission was shown to occur at locations where young, weaned, and comingled calves were maintained. Serological characterization of archived sera suggested that IDV has been circulating in the Mississippi cattle populations since at least 2004. Continuous surveillance is needed to monitor the evolution and epidemiology of IDV in the bovine population.",,"['Ferguson, Lucas', 'Eckard, Laura', 'Epperson, William B.', 'Long, Li-Ping', 'Smith, David', 'Huston, Carla', 'Genova, Suzanne', 'Webby, Richard', 'Wan, Xiu-Feng']",,,,
,PMC,IFITM Proteins Restrict HIV-1 Infection by Antagonizing the Envelope Glycoprotein,http://dx.doi.org/10.1016/j.celrep.2015.08.055,PMC4602366,,,"The interferon-induced transmembrane (IFITM) proteins have been recently shown to restrict HIV-1 and other viruses. Here we provide evidence that IFITM proteins, particularly IFITM2 and IFITM3, specifically antagonize the HIV-1 envelope glycoprotein (Env), thereby inhibiting viral infection. IFITM proteins interact with HIV-1 Env in viral producer cells, leading to impaired Env processing and virion incorporation. Notably, the level of IFITM incorporation into HIV-1 virions does not strictly correlate with the extent of inhibition. Prolonged passage of HIV-1 in IFITM-expressing T lymphocytes leads to emergence of Env mutants that overcome IFITM restriction. The ability of IFITMs to inhibit cell-to-cell infection can be extended to HIV-1 primary isolates, HIV-2 and SIVs; however, the extent of inhibition appears to be virus strain-dependent. Overall, our study uncovers a mechanism by which IFITM proteins specifically antagonize HIV-1 Env to restrict HIV-1 infection, and provides insight into the specialized role of IFITMs in HIV infection.",,"['Yu, Jingyou', 'Li, Minghua', 'Wilkins, Jordan', 'Ding, Shilei', 'Swartz, Talia H.', 'Esposito, Anthony M.', 'Zheng, Yi-Min', 'Freed, Eric O.', 'Liang, Chen', 'Chen, Benjamin K.', 'Liu, Shan-Lu']",,,,
,PMC,Influenza A virus transmission via respiratory aerosols or droplets as it relates to pandemic potential,http://dx.doi.org/10.1093/femsre/fuv039,PMC5006288,,,"Many respiratory viruses of humans originate from animals. For instance, there are now eight paramyxoviruses, four coronaviruses and four orthomxoviruses that cause recurrent epidemics in humans but were once confined to other hosts. In the last decade, several members of the same virus families have jumped the species barrier from animals to humans. Fortunately, these viruses have not become established in humans, because they lacked the ability of sustained transmission between humans. However, these outbreaks highlighted the lack of understanding of what makes a virus transmissible. In part triggered by the relatively high frequency of occurrence of influenza A virus zoonoses and pandemics, the influenza research community has started to investigate the viral genetic and biological traits that drive virus transmission via aerosols or respiratory droplets between mammals. Here we summarize recent discoveries on the genetic and phenotypic traits required for airborne transmission of zoonotic influenza viruses of subtypes H5, H7 and H9 and pandemic viruses of subtypes H1, H2 and H3. Increased understanding of the determinants and mechanisms of respiratory virus transmission is not only key from a basic scientific perspective, but may also aid in assessing the risks posed by zoonotic viruses to human health, and preparedness for such risks.",,"['Richard, Mathilde', 'Fouchier, Ron A.M.']",,,,
,PMC,Human Vaccines & Immunotherapeutics: News,http://dx.doi.org/10.1080/21645515.2015.1083787,PMC4635696,,,,,,,,,
,PMC,Setting Healthcare Priorities at the Macro and Meso Levels: A Framework for Evaluation,http://dx.doi.org/10.15171/ijhpm.2015.167,PMC4629697,,,"Background: Priority setting in healthcare is a key determinant of health system performance. However, there is no widely accepted priority setting evaluation framework. We reviewed literature with the aim of developing and proposing a framework for the evaluation of macro and meso level healthcare priority setting practices. Methods: We systematically searched Econlit, PubMed, CINAHL, and EBSCOhost databases and supplemented this with searches in Google Scholar, relevant websites and reference lists of relevant papers. A total of 31 papers on evaluation of priority setting were identified. These were supplemented by broader theoretical literature related to evaluation of priority setting. A conceptual review of selected papers was undertaken. Results: Based on a synthesis of the selected literature, we propose an evaluative framework that requires that priority setting practices at the macro and meso levels of the health system meet the following conditions: (1) Priority setting decisions should incorporate both efficiency and equity considerations as well as the following outcomes; (a) Stakeholder satisfaction, (b) Stakeholder understanding, (c) Shifted priorities (reallocation of resources), and (d) Implementation of decisions. (2) Priority setting processes should also meet the procedural conditions of (a) Stakeholder engagement, (b) Stakeholder empowerment, (c) Transparency, (d) Use of evidence, (e) Revisions, (f) Enforcement, and (g) Being grounded on community values. Conclusion: Available frameworks for the evaluation of priority setting are mostly grounded on procedural requirements, while few have included outcome requirements. There is, however, increasing recognition of the need to incorporate both consequential and procedural considerations in priority setting practices. In this review, we adapt an integrative approach to develop and propose a framework for the evaluation of priority setting practices at the macro and meso levels that draws from these complementary schools of thought.",,"['Barasa, Edwine W.', 'Molyneux, Sassy', 'English, Mike', 'Cleary, Susan']",,,,
,PMC,Point-Counterpoint: Large Multiplex PCR Panels Should Be First-Line Tests for Detection of Respiratory and Intestinal Pathogens,http://dx.doi.org/10.1128/JCM.00382-15,PMC4572537,,,"The first FDA-approved multiplex PCR panel for a large number of respiratory pathogens was introduced in 2008. Since then, other PCR panels for detection of several respiratory and gastrointestinal pathogens have been approved by the FDA and are commercially available, and more such panels are likely to become available. These assays detect 12 to 20 pathogens, and some include pathogens that typically cause different manifestations of infection, although they infect the same organ system. Some of these tests are labor-intensive, while others require little labor, and all of them are expensive, both for the laboratory and for the patient or insurer. They include a bundle of tests with limited or no options for selecting which tests will be performed. Laboratories and hospitals have adopted different strategies for offering these assays. Some have implemented strategies to limit the use of the tests, such as limiting the frequency with which patients can be tested, restricting testing to specific groups of patients (e.g., immunocompromised patients), or providing education to encourage the use of less expensive tests before using large multiplex panels. Others have offered these assays without limiting their use, either relying on the ordering provider to exercise good judgment or because such assays are thought to be appropriate for first-line diagnostic testing. In this Point-Counterpoint, Paul Schreckenberger of Loyola University Medical Center explains why his laboratory offers these assays without restriction. Alex McAdam of Boston's Children Hospital explains the concerns about the use of these assays as first-line tests and why some limitations on their use might be appropriate.",,"['Schreckenberger, Paul C.', 'McAdam, Alexander J.']",,,,
,PMC,"Mumps Virus Is Released from the Apical Surface of Polarized Epithelial Cells, and the Release Is Facilitated by a Rab11-Mediated Transport System",http://dx.doi.org/10.1128/JVI.02048-15,PMC4645333,,,"Mumps virus (MuV) is an airborne virus that causes a systemic infection in patients. In vivo, the epithelium is a major replication site of MuV, and thus, the mode of MuV infection of epithelial cells is a subject of interest. Our data in the present study showed that MuV entered polarized epithelial cells via both the apical and basolateral surfaces, while progeny viruses were predominantly released from the apical surface. In polarized cells, intracellular transport of viral ribonucleoprotein (vRNP) complexes was dependent on Rab11-positive endosomes, and vRNP complexes were transported to the apical membrane. Expression of a dominant negative form of Rab11 (Rab11S25N) reduced the progeny virus release in polarized cells but not in nonpolarized cells. Although in this way these effects were correlated with cell polarity, Rab11S25N did not modulate the direction of virus release from the apical surface. Therefore, our data suggested that Rab11 is not a regulator of selective apical release of MuV, although it acts as an activator of virus release from polarized epithelial cells. In addition, our data and previous studies on Sendai virus, respiratory syncytial virus, and measles virus suggested that selective apical release from epithelial cells is used by many paramyxoviruses, even though they cause either a systemic infection or a local respiratory infection. IMPORTANCE Mumps virus (MuV) is the etiological agent of mumps and causes a systemic infection. However, the precise mechanism by which MuV breaks through the epithelial barriers and achieves a systemic infection remains unclear. In the present study, we show that the entry of MuV is bipolar, while the release is predominantly from the apical surface in polarized epithelial cells. In addition, the release of progeny virus was facilitated by a Rab11-positive recycling endosome and microtubule network. Our data provide important insights into the mechanism of transmission and pathogenesis of MuV.",,"['Katoh, Hiroshi', 'Nakatsu, Yuichiro', 'Kubota, Toru', 'Sakata, Masafumi', 'Takeda, Makoto', 'Kidokoro, Minoru']",,,,
,PMC,Replication and Transmission of the Novel Bovine Influenza D Virus in a Guinea Pig Model,http://dx.doi.org/10.1128/JVI.01630-15,PMC4645331,,,"Influenza D virus (FLUDV) is a novel influenza virus that infects cattle and swine. The goal of this study was to investigate the replication and transmission of bovine FLUDV in guinea pigs. Following direct intranasal inoculation of animals, the virus was detected in nasal washes of infected animals during the first 7 days postinfection. High viral titers were obtained from nasal turbinates and lung tissues of directly inoculated animals. Further, bovine FLUDV was able to transmit from the infected guinea pigs to sentinel animals by means of contact and not by aerosol dissemination under the experimental conditions tested in this study. Despite exhibiting no clinical signs, infected guinea pigs developed seroconversion and the viral antigen was detected in lungs of animals by immunohistochemistry. The observation that bovine FLUDV replicated in the respiratory tract of guinea pigs was similar to observations described previously in studies of gnotobiotic calves and pigs experimentally infected with bovine FLUDV but different from those described previously in experimental infections in ferrets and swine with a swine FLUDV, which supported virus replication only in the upper respiratory tract and not in the lower respiratory tract, including lung. Our study established that guinea pigs could be used as an animal model for studying this newly emerging influenza virus. IMPORTANCE Influenza D virus (FLUDV) is a novel emerging pathogen with bovine as its primary host. The epidemiology and pathogenicity of the virus are not yet known. FLUDV also spreads to swine, and the presence of FLUDV-specific antibodies in humans could indicate that there is a potential for zoonosis. Our results showed that bovine FLUDV replicated in the nasal turbinate and lungs of guinea pigs at high titers and was also able to transmit from an infected animal to sentinel animals by contact. The fact that bovine FLUDV replicated productively in both the upper and lower respiratory tracts of guinea pigs, similarly to virus infection in its native host, demonstrates that guinea pigs would be a suitable model host to study the replication and transmission potential of bovine FLUDV.",,"['Sreenivasan, Chithra', 'Thomas, Milton', 'Sheng, Zizhang', 'Hause, Ben M.', 'Collin, Emily A.', 'Knudsen, David E. B.', 'Pillatzki, Angela', 'Nelson, Eric', 'Wang, Dan', 'Kaushik, Radhey S.', 'Li, Feng']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus ORF7a Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel Mechanism of Glycosylation Interference,http://dx.doi.org/10.1128/JVI.02274-15,PMC4645327,,,"Severe acute respiratory syndrome (SARS) emerged in November 2002 as a case of atypical pneumonia in China, and the causative agent of SARS was identified to be a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV). Bone marrow stromal antigen 2 (BST-2; also known as CD317 or tetherin) was initially identified to be a pre-B-cell growth promoter, but it also inhibits the release of virions of the retrovirus human immunodeficiency virus type 1 (HIV-1) by tethering budding virions to the host cell membrane. Further work has shown that BST-2 restricts the release of many other viruses, including the human coronavirus 229E (hCoV-229E), and the genomes of many of these viruses encode BST-2 antagonists to overcome BST-2 restriction. Given the previous studies on BST-2, we aimed to determine if BST-2 has the ability to restrict SARS-CoV and if the SARS-CoV genome encodes any proteins that modulate BST-2's antiviral function. Through an in vitro screen, we identified four potential BST-2 modulators encoded by the SARS-CoV genome: the papain-like protease (PL(Pro)), nonstructural protein 1 (nsp1), ORF6, and ORF7a. As the function of ORF7a in SARS-CoV replication was previously unknown, we focused our study on ORF7a. We found that BST-2 does restrict SARS-CoV, but the loss of ORF7a leads to a much greater restriction, confirming the role of ORF7a as an inhibitor of BST-2. We further characterized the mechanism of BST-2 inhibition by ORF7a and found that ORF7a localization changes when BST-2 is overexpressed and ORF7a binds directly to BST-2. Finally, we also show that SARS-CoV ORF7a blocks the restriction activity of BST-2 by blocking the glycosylation of BST-2. IMPORTANCE The severe acute respiratory syndrome coronavirus (SARS-CoV) emerged from zoonotic sources in 2002 and caused over 8,000 infections and 800 deaths in 37 countries around the world. Identifying host factors that regulate SARS-CoV pathogenesis is critical to understanding how this lethal virus causes disease. We have found that BST-2 is capable of restricting SARS-CoV release from cells; however, we also identified a SARS-CoV protein that inhibits BST-2 function. We show that the SARS-CoV protein ORF7a inhibits BST-2 glycosylation, leading to a loss of BST-2's antiviral function.",,"['Taylor, Justin K.', 'Coleman, Christopher M.', 'Postel, Sandra', 'Sisk, Jeanne M.', 'Bernbaum, John G.', 'Venkataraman, Thiagarajan', 'Sundberg, Eric J.', 'Frieman, Matthew B.']",,,,
,PMC,Evidence for an Ancestral Association of Human Coronavirus 229E with Bats,http://dx.doi.org/10.1128/JVI.01755-15,PMC4645311,,,"We previously showed that close relatives of human coronavirus 229E (HCoV-229E) exist in African bats. The small sample and limited genomic characterizations have prevented further analyses so far. Here, we tested 2,087 fecal specimens from 11 bat species sampled in Ghana for HCoV-229E-related viruses by reverse transcription-PCR (RT-PCR). Only hipposiderid bats tested positive. To compare the genetic diversity of bat viruses and HCoV-229E, we tested historical isolates and diagnostic specimens sampled globally over 10 years. Bat viruses were 5- and 6-fold more diversified than HCoV-229E in the RNA-dependent RNA polymerase (RdRp) and spike genes. In phylogenetic analyses, HCoV-229E strains were monophyletic and not intermixed with animal viruses. Bat viruses formed three large clades in close and more distant sister relationships. A recently described 229E-related alpaca virus occupied an intermediate phylogenetic position between bat and human viruses. According to taxonomic criteria, human, alpaca, and bat viruses form a single CoV species showing evidence for multiple recombination events. HCoV-229E and the alpaca virus showed a major deletion in the spike S1 region compared to all bat viruses. Analyses of four full genomes from 229E-related bat CoVs revealed an eighth open reading frame (ORF8) located at the genomic 3′ end. ORF8 also existed in the 229E-related alpaca virus. Reanalysis of HCoV-229E sequences showed a conserved transcription regulatory sequence preceding remnants of this ORF, suggesting its loss after acquisition of a 229E-related CoV by humans. These data suggested an evolutionary origin of 229E-related CoVs in hipposiderid bats, hypothetically with camelids as intermediate hosts preceding the establishment of HCoV-229E. IMPORTANCE The ancestral origins of major human coronaviruses (HCoVs) likely involve bat hosts. Here, we provide conclusive genetic evidence for an evolutionary origin of the common cold virus HCoV-229E in hipposiderid bats by analyzing a large sample of African bats and characterizing several bat viruses on a full-genome level. Our evolutionary analyses show that animal and human viruses are genetically closely related, can exchange genetic material, and form a single viral species. We show that the putative host switches leading to the formation of HCoV-229E were accompanied by major genomic changes, including deletions in the viral spike glycoprotein gene and loss of an open reading frame. We reanalyze a previously described genetically related alpaca virus and discuss the role of camelids as potential intermediate hosts between bat and human viruses. The evolutionary history of HCoV-229E likely shares important characteristics with that of the recently emerged highly pathogenic Middle East respiratory syndrome (MERS) coronavirus.",,"['Corman, Victor Max', 'Baldwin, Heather J.', 'Tateno, Adriana Fumie', 'Zerbinati, Rodrigo Melim', 'Annan, Augustina', 'Owusu, Michael', 'Nkrumah, Evans Ewald', 'Maganga, Gael Darren', 'Oppong, Samuel', 'Adu-Sarkodie, Yaw', 'Vallo, Peter', 'da Silva Filho, Luiz Vicente Ribeiro Ferreira', 'Leroy, Eric M.', 'Thiel, Volker', 'van der Hoek, Lia', 'Poon, Leo L. M.', 'Tschapka, Marco', 'Drosten, Christian', 'Drexler, Jan Felix']",,,,
,PMC,Cell Walls and the Convergent Evolution of the Viral Envelope,http://dx.doi.org/10.1128/MMBR.00017-15,PMC4651029,,,"Why some viruses are enveloped while others lack an outer lipid bilayer is a major question in viral evolution but one that has received relatively little attention. The viral envelope serves several functions, including protecting the RNA or DNA molecule(s), evading recognition by the immune system, and facilitating virus entry. Despite these commonalities, viral envelopes come in a wide variety of shapes and configurations. The evolution of the viral envelope is made more puzzling by the fact that nonenveloped viruses are able to infect a diverse range of hosts across the tree of life. We reviewed the entry, transmission, and exit pathways of all (101) viral families on the 2013 International Committee on Taxonomy of Viruses (ICTV) list. By doing this, we revealed a strong association between the lack of a viral envelope and the presence of a cell wall in the hosts these viruses infect. We were able to propose a new hypothesis for the existence of enveloped and nonenveloped viruses, in which the latter represent an adaptation to cells surrounded by a cell wall, while the former are an adaptation to animal cells where cell walls are absent. In particular, cell walls inhibit viral entry and exit, as well as viral transport within an organism, all of which are critical waypoints for successful infection and spread. Finally, we discuss how this new model for the origin of the viral envelope impacts our overall understanding of virus evolution.",,"['Buchmann, Jan P.', 'Holmes, Edward C.']",,,,
,PMC,Clinical utility of a near patient care microarray based diagnostic test for influenza and respiratory syncytial virus infections,,PMC4659065,,,"In primary care medicine, establishing a diagnosis of influenza and respiratory syncytial virus (RSV) infections is usually based on clinical history and physical examination as well as a consideration of time of the year and circulating respiratory viruses in the community. Methods: We tested the potential clinical samples using the automated molecular assay which included rapid influenza diagnostic test, Rapid Immunochromatographic Antigen Test, Verigene Respiratory Virus Plus Nucleic Acid Test, BD Veritor(TM) System for Rapid Detection of RSV in the paediatric setting for diagnosis of influenza and respiratory syntactical virus infections when testing was done by the paediatrician seeing the patient. Results: Principally, with respect influenza virus specificity and sensitivity for RIAT were 100% and 68.8%; compared to 100% and 100%, respectively for RV(+). The specificity and sensitivity for 92.23% and 98% for BD Veritor(TM) System for Rapid Detection of RSV as compared to 96.6% and 98.42% for RIDT. Conclusion: Therefore, this study confirms the clinical utility of RV(+) in the pediatric setting.",,"['Chen, Xiu-Hong', 'Wang, Ji-Hua', 'Yao, Xiao-Hong']",,,,
,PMC,Coxsackievirus can exploit LC3 in both autophagy-dependent and -independent manners in vivo,http://dx.doi.org/10.1080/15548627.2015.1063769,PMC4590631,,,"RNA viruses modify intracellular membranes to produce replication scaffolds. In pancreatic cells, coxsackievirus B3 (CVB3) hijacks membranes from the autophagy pathway, and in vivo disruption of acinar cell autophagy dramatically delays CVB3 replication. This is reversed by expression of GFP-LC3, indicating that CVB3 may acquire membranes from an alternative, autophagy-independent, source(s). Herein, using 3 recombinant CVB3s (rCVB3s) encoding different proteins (proLC3, proLC3(G120A), or ATG4B(C74A)), we show that CVB3 is, indeed, flexible in its utilization of cellular membranes. When compared with a control rCVB3, all 3 viruses replicated to high titers in vivo, and caused severe pancreatitis. Most importantly, each virus appeared to subvert membranes in a unique manner. The proLC3 virus produced a large quantity of LC3-I which binds to phosphatidylethanolamine (PE), affording access to the autophagy pathway. The proLC3(G120A) protein cannot attach to PE, and instead binds to the ER-resident protein SEL1L, potentially providing an autophagy-independent source of membranes. Finally, the ATG4B(C74A) protein sequestered host cell LC3-I, causing accumulation of immature phagophores, and massive membrane rearrangement. Taken together, our data indicate that some RNA viruses can exploit a variety of different intracellular membranes, potentially maximizing their replication in each of the diverse cell types that they infect in vivo.",,"['Alirezaei, Mehrdad', 'Flynn, Claudia T', 'Wood, Malcolm R', 'Harkins, Stephanie', 'Whitton, J Lindsay']",,,,
,PMC,Hematopoietic and Non-Hematopoietic Cells Promote Type I Interferon- and Toll-like Receptor 7-dependent Monocytosis During Low-dose Lymphocytic Choriomeningitis Virus Infection,http://dx.doi.org/10.1002/eji.201445331,PMC4675142,,,"Release of inflammatory monocytes from the bone marrow (BM) into the blood is an important physiological response to infection, but the mechanisms regulating this phenomenon during viral infection are not completely defined. Here, we show that low-dose infection with Lymphocytic Choriomeningitis Virus (LCMV) caused rapid, transient inflammatory monocytosis that required type I IFN and TLR7 signaling. Both signals were critical for induction of IFN stimulated gene expression and CCR2 ligand upregulation in the BM microenvironment in response to LCMV infection. Experiments utilizing bone marrow chimeric mice demonstrated that type I IFN- and TLR7-signaling on either hematopoietic or non-hematopoietic cells was sufficient to initiate monocytosis in response to LCMV infection. BM plasmacytoid dendritic cells (pDC) generated type I IFN directly ex vivo, suggesting that pDC are a hematopoietic contributor of type I IFN in the BM early during LCMV infection. Overall, we describe novel roles for type I IFN and TLR7 signaling in non-hematopoietic cells and BM pDC in directing interferon stimulated gene and CCR2 ligand expression in the BM to initiate an increase in blood inflammatory monocytes during viral infection.",,"['Buechler, Matthew B.', 'Gessay, Griffin M.', 'Srivastava, Shivani', 'Campbell, Daniel J.', 'Hamerman, Jessica A.']",,,,
,PMC,ELL Protein-associated Factor 2 (EAF2) Inhibits Transforming Growth Factor β Signaling through a Direct Interaction with Smad3,http://dx.doi.org/10.1074/jbc.M115.663542,PMC4646248,,,"A series of in vitro and in vivo studies has shown that EAF2 can affect multiple signaling pathways involved in cellular processes. However, the molecular mechanisms underlying its effects have remained elusive. Here we report the discovery of a new functional link between EAF2 and TGF-β signaling. Promoter reporter assays indicated that EAF2 suppresses Smad3 transcriptional activity, resulting in inhibition of TGF-β signaling. Coimmunoprecipitation assays showed that EAF2 specifically interacts with Smad3 in vitro and in vivo but not with other Smad proteins. In addition, we observed that EAF2 binding does not alter Smad3 phosphorylation but causes Smad3 cytoplasmic retention, competes with Smad4 for binding to Smad3, and prevents p300-Smad3 complex formation. Furthermore, we demonstrated that EAF2 suppresses both TGF-β-induced G(1) cell cycle arrest and TGF-β-induced cell migration. This study identifies and characterizes a novel repressor of TGF-β signaling.",,"['Liu, Xing', 'Chen, Zhu', 'Ouyang, Gang', 'Song, Tieshan', 'Liang, Huageng', 'Liu, Wei', 'Xiao, Wuhan']",,,,
,PMC,Annexin A2 regulates autophagy in Pseudomonas aeruginosa infection through Akt1-mTOR-ULK1/2 signaling pathway,http://dx.doi.org/10.4049/jimmunol.1500967,PMC4592832,,,"Earlier studies reported that a cell membrane protein Annexin A2 (AnxA2) plays multiple roles in the development, invasion and metastasis of cancer. Recent studies have demonstrated that AnxA2 also functions in immunity against infection, but the underlying mechanism remains largely elusive. Using a mouse infection model, we now reveal a crucial role of AnxA2 in host defense against Pseudomonas aeruginosa (Pa), as anxa2(−/−) mice manifested severe lung injury, systemic dissemination, and increased mortality compared to wild-type (WT) littermates. In addition, anxa2(−/−) mice exhibited elevated inflammatory cytokines (TNF-α, IL-6, IL-1β and IFN-γ), decreased bacterial clearance by macrophages, and increased superoxide release in the lung. We further identified an unexpected molecular interaction between AnxA2 and Fam13A (Family with sequence similarity 13, member A), which activated Rho GTPase. P. aeruginosa infection induced autophagosome formation by inhibiting Akt1 and mTOR. Our results indicate that AnxA2 regulates autophagy and thereby contributing to host immunity against bacteria through Akt1-mTOR-ULK1/2 signaling pathway.",,"['Li, Rongpeng', 'Tan, Shirui', 'Yu, Min', 'Jundt, Michael C.', 'Zhang, Shuang', 'Wu, Min']",,,,
,PMC,Resident-memory CD8 T cells express high-affinity T cell receptors,http://dx.doi.org/10.4049/jimmunol.1501521,PMC4592826,,,"Tissue-resident memory T (T(RM)) cells serve as vanguards of anti-microbial host defense in nonlymphoid tissues, particularly at barrier epithelia and in organs with non-renewable cell types (e.g., brain). Here, we asked whether an augmented ability to sense antigen complemented their role as early alarms of pathogen invasion. Using mouse polyomavirus (MPyV), we show that brain-resident MPyV-specific CD8 T cells, unlike memory cells in the spleen, progressively increase binding to MHC class I tetramers and CD8 co-receptor expression. Using the two-dimensional micropipette adhesion frequency assay, we show that T(RM) cells in brain, as well as in kidney, express up to 20-fold higher affinity T cell receptors (TCRs) than splenic memory T cells, whereas effector cells express TCRs of similar high affinity in all organs. Together, these data demonstrate that T(RM) cells retain high TCR affinity, which endows them with the high antigen sensitivity needed for front-line defense against infectious agents.",,"['Frost, Elizabeth L.', 'Kersh, Anna E.', 'Evavold, Brian D.', 'Lukacher, Aron E.']",,,,
,PMC,Encephalomyocarditis Virus 3C Protease Relieves TRAF Family Member-associated NF-κB Activator (TANK) Inhibitory Effect on TRAF6-mediated NF-κB Signaling through Cleavage of TANK,http://dx.doi.org/10.1074/jbc.M115.660761,PMC4646013,,,"TRAF family member-associated NF-κB activator (TANK) is a negative regulator of canonical NF-κB signaling in the Toll-like receptor- and B-cell receptor-mediated signaling pathways. However, functions of TANK in viral infection-mediated NF-κB activation remain unclear. Here, we reported that TANK was cleaved by encephalomyocarditis virus 3C at the 197 and 291 glutamine residues, which depends on its cysteine protease activity. In addition, encephalomyocarditis virus 3C impaired the ability of TANK to inhibit TRAF6-mediated NF-κB signaling. Interestingly, we found that several viral proteases encoded by the foot and mouth disease virus, porcine reproductive and respiratory syndrome virus, and equine arteritis virus also cleaved TANK. Our results suggest that TANK is a novel target of some viral proteases, indicating that some positive RNA viruses have evolved to utilize their major proteases to regulate NF-κB activation.",,"['Huang, Li', 'Liu, Qinfang', 'Zhang, Lijie', 'Zhang, Quan', 'Hu, Liang', 'Li, Changyao', 'Wang, Shengnan', 'Li, Jiangnan', 'Zhang, Yuanfeng', 'Yu, Huibin', 'Wang, Yan', 'Zhong, Zhaohua', 'Xiong, Tao', 'Xia, Xueshan', 'Wang, Xiaojun', 'Yu, Li', 'Deng, Guohua', 'Cai, Xuehui', 'Cui, Shangjin', 'Weng, Changjiang']",,,,
,PMC,Standing your Ground to Exoribonucleases: Function of Flavivirus Long Non-coding RNAs,http://dx.doi.org/10.1016/j.virusres.2015.09.009,PMC4744573,,,"Members of the Flaviviridae (e.g. Dengue virus, West Nile virus, and Hepatitis C virus) contain a positive-sense RNA genome that encodes a large polyprotein. It is now also clear most if not all of these viruses also produce an abundant subgenomic long non-coding RNA. These non-coding RNAs, which are called subgenomicflavivirus RNAs (sfRNAs) or Xrn1-resistant RNAs (xrRNAs), are stable decay intermediates generated from the viral genomic RNA through the stalling of the cellular exoribonuclease Xrn1 at highly structured regions. Several functions of these flavivirus long non-coding RNAs have been revealed in recent years. The generation of these sfRNAs/xrRNAs from viral transcripts results in the repression of Xrn1 and the dysregulation of cellular mRNA stability. The abundant sfRNAs also serve directly as a decoy for important cellular protein regulators of the interferon and RNA interference antiviral pathways. Thus the generation of long non-coding RNAs from flaviviruses, hepaciviruses and pestiviruses likely disrupts aspects of innate immunity and may directly contribute to viral replication, cytopathology and pathogenesis.",,"['Charley, Phillida A.', 'Wilusz, Jeffrey']",,,,
,PMC,Escape From Monoclonal Antibody Neutralization Affects Henipavirus Fitness In Vitro and In Vivo,http://dx.doi.org/10.1093/infdis/jiv449,PMC4704671,,,"Henipaviruses are zoonotic viruses that can cause severe and acute respiratory diseases and encephalitis in humans. To date, no vaccine or treatments are approved for human use. The presence of neutralizing antibodies is a strong correlate of protection against lethal disease in animals. However, since RNA viruses are prone to high mutation rates, the possibility that these viruses will escape neutralization remains a potential concern. In the present study, we generated neutralization-escape mutants, using 6 different monoclonal antibodies, and studied the effect of these neutralization-escape mutations on in vitro and in vivo fitness. These data provide a mechanism for overcoming neutralization escape by use of cocktails of cross-neutralizing monoclonal antibodies that recognize residues within the glycoprotein that are important for virus replication and virulence.",,"['Borisevich, Viktoriya', 'Lee, Benhur', 'Hickey, Andrew', 'DeBuysscher, Blair', 'Broder, Christopher C.', 'Feldmann, Heinz', 'Rockx, Barry']",,,,
,PMC,Inflammation-associated genes: risks and benefits to Foxp3(+) regulatory T-cell function,http://dx.doi.org/10.1111/imm.12507,PMC4582961,,,"Foxp3(+) regulatory T (Treg) cells prevent the development of autoimmunity and immunopathology, as well as maintaining homeostasis and tolerance to commensal microorganisms. The suppressive activity of Treg cells is their defining characteristic, generating great interest in their therapeutic potential. However, suppressive and effector functions are not entirely exclusive. Considerable evidence points to the ability of supposedly anti-inflammatory Foxp3-expressing Treg cells to also express transcription factors that have been characterized as cardinal drivers of T effector cell function. We will consider the mounting evidence that Treg cells can function in non-suppressive capacities and review the impetus for this functional change, its relevance to developing immune and autoimmune responses and its significance to the development of Treg-based therapies.",,"['O’Connor, Richard A', 'Anderton, Stephen M']",,,,
,PMC,"The Interferon-induced Transmembrane Proteins, IFITM1, IFITM2, and IFITM3 Inhibit Hepatitis C Virus Entry",http://dx.doi.org/10.1074/jbc.M115.657346,PMC4646249,,,"The interferon-induced transmembrane (IFITM) family of proteins have recently been identified as important host effector molecules of the type I interferon response against viruses. IFITM1 has been identified as a potent antiviral effector against hepatitis C virus (HCV), whereas the related family members IFITM2 and IFITM3 have been described to have antiviral effects against a broad range of RNA viruses. Here, we demonstrate that IFITM2 and IFITM3 play an integral role in the interferon response against HCV and act at the level of late entry stages of HCV infection. We have established that in hepatocytes, IFITM2 and IFITM3 localize to the late and early endosomes, respectively, as well as the lysosome. Furthermore, we have demonstrated that S-palmitoylation of all three IFITM proteins is essential for anti-HCV activity, whereas the conserved tyrosine residue in the N-terminal domain of IFITM2 and IFITM3 plays a significant role in protein localization. However, this tyrosine was found to be dispensable for anti-HCV activity, with mutation of the tyrosine resulting in an IFITM1-like phenotype with the retention of anti-HCV activity and co-localization of IFITM2 and IFITM3 with CD81. In conclusion, we propose that the IFITM proteins act in a coordinated manner to restrict HCV infection by targeting the endocytosed HCV virion for lysosomal degradation and demonstrate that the actions of the IFITM proteins are indeed virus and cell-type specific.",,"['Narayana, Sumudu K.', 'Helbig, Karla J.', 'McCartney, Erin M.', 'Eyre, Nicholas S.', 'Bull, Rowena A.', 'Eltahla, Auda', 'Lloyd, Andrew R.', 'Beard, Michael R.']",,,,
,PMC,A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform,http://dx.doi.org/10.1128/JVI.01815-15,PMC4645655,,,"In 2012, the first cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) were identified. Since then, more than 1,000 cases of MERS-CoV infection have been confirmed; infection is typically associated with considerable morbidity and, in approximately 30% of cases, mortality. Currently, there is no protective vaccine available. Replication-competent recombinant measles virus (MV) expressing foreign antigens constitutes a promising tool to induce protective immunity against corresponding pathogens. Therefore, we generated MVs expressing the spike glycoprotein of MERS-CoV in its full-length (MERS-S) or a truncated, soluble variant of MERS-S (MERS-solS). The genes encoding MERS-S and MERS-solS were cloned into the vaccine strain MV(vac2) genome, and the respective viruses were rescued (MV(vac2)-CoV-S and MV(vac2)-CoV-solS). These recombinant MVs were amplified and characterized at passages 3 and 10. The replication of MV(vac2)-CoV-S in Vero cells turned out to be comparable to that of the control virus MV(vac2)-GFP (encoding green fluorescent protein), while titers of MV(vac2)-CoV-solS were impaired approximately 3-fold. The genomic stability and expression of the inserted antigens were confirmed via sequencing of viral cDNA and immunoblot analysis. In vivo, immunization of type I interferon receptor-deficient (IFNAR(−/−))-CD46Ge mice with 2 × 10(5) 50% tissue culture infective doses of MV(vac2)-CoV-S(H) or MV(vac2)-CoV-solS(H) in a prime-boost regimen induced robust levels of both MV- and MERS-CoV-neutralizing antibodies. Additionally, induction of specific T cells was demonstrated by T cell proliferation, antigen-specific T cell cytotoxicity, and gamma interferon secretion after stimulation of splenocytes with MERS-CoV-S presented by murine dendritic cells. MERS-CoV challenge experiments indicated the protective capacity of these immune responses in vaccinated mice. IMPORTANCE Although MERS-CoV has not yet acquired extensive distribution, being mainly confined to the Arabic and Korean peninsulas, it could adapt to spread more readily among humans and thereby become pandemic. Therefore, the development of a vaccine is mandatory. The integration of antigen-coding genes into recombinant MV resulting in coexpression of MV and foreign antigens can efficiently be achieved. Thus, in combination with the excellent safety profile of the MV vaccine, recombinant MV seems to constitute an ideal vaccine platform. The present study shows that a recombinant MV expressing MERS-S is genetically stable and induces strong humoral and cellular immunity against MERS-CoV in vaccinated mice. Subsequent challenge experiments indicated protection of vaccinated animals, illustrating the potential of MV as a vaccine platform with the potential to target emerging infections, such as MERS-CoV.",,"['Malczyk, Anna H.', 'Kupke, Alexandra', 'Prüfer, Steffen', 'Scheuplein, Vivian A.', 'Hutzler, Stefan', 'Kreuz, Dorothea', 'Beissert, Tim', 'Bauer, Stefanie', 'Hubich-Rau, Stefanie', 'Tondera, Christiane', 'Eldin, Hosam Shams', 'Schmidt, Jörg', 'Vergara-Alert, Júlia', 'Süzer, Yasemin', 'Seifried, Janna', 'Hanschmann, Kay-Martin', 'Kalinke, Ulrich', 'Herold, Susanne', 'Sahin, Ugur', 'Cichutek, Klaus', 'Waibler, Zoe', 'Eickmann, Markus', 'Becker, Stephan', 'Mühlebach, Michael D.']",,,,
,PMC,Computational and Functional Analysis of the Virus-Receptor Interface Reveals Host Range Trade-Offs in New World Arenaviruses,http://dx.doi.org/10.1128/JVI.01408-15,PMC4645654,,,"Animal viruses frequently cause zoonotic disease in humans. As these viruses are highly diverse, evaluating the threat that they pose remains a major challenge, and efficient approaches are needed to rapidly predict virus-host compatibility. Here, we develop a combined computational and experimental approach to assess the compatibility of New World arenaviruses, endemic in rodents, with the host TfR1 entry receptors of different potential new host species. Using signatures of positive selection, we identify a small motif on rodent TfR1 that conveys species specificity to the entry of viruses into cells. However, we show that mutations in this region affect the entry of each arenavirus differently. For example, a human single nucleotide polymorphism (SNP) in this region, L212V, makes human TfR1 a weaker receptor for one arenavirus, Machupo virus, but a stronger receptor for two other arenaviruses, Junin and Sabia viruses. Collectively, these findings set the stage for potential evolutionary trade-offs, where natural selection for resistance to one virus may make humans or rodents susceptible to other arenavirus species. Given the complexity of this host-virus interplay, we propose a computational method to predict these interactions, based on homology modeling and computational docking of the virus-receptor protein-protein interaction. We demonstrate the utility of this model for Machupo virus, for which a suitable cocrystal structural template exists. Our model effectively predicts whether the TfR1 receptors of different species will be functional receptors for Machupo virus entry. Approaches such at this could provide a first step toward computationally predicting the “host jumping” potential of a virus into a new host species. IMPORTANCE We demonstrate how evolutionary trade-offs may exist in the dynamic evolutionary interplay between viruses and their hosts, where natural selection for resistance to one virus could make humans or rodents susceptible to other virus species. We present an algorithm that predicts which species have cell surface receptors that make them susceptible to Machupo virus, based on computational docking of protein structures. Few molecular models exist for predicting the risk of spillover of a particular animal virus into humans or new animal populations. Our results suggest that a combination of evolutionary analysis, structural modeling, and experimental verification may provide an efficient approach for screening and assessing the potential spillover risks of viruses circulating in animal populations.",,"['Kerr, Scott A.', 'Jackson, Eleisha L.', 'Lungu, Oana I.', 'Meyer, Austin G.', 'Demogines, Ann', 'Ellington, Andrew D.', 'Georgiou, George', 'Wilke, Claus O.', 'Sawyer, Sara L.']",,,,
,PMC,Bilirubin encephalopathy in a domestic shorthair cat with increased osmotic fragility and cholangiohepatitis,http://dx.doi.org/10.1177/0300985815603433,PMC4785093,,,"A 7-month-old female domestic shorthair (DSH) cat was diagnosed with chronic regenerative hemolytic anemia characterized by increased osmotic fragility (OF) of unknown etiology. At 13 months of age, the cat was evaluated for acute collapse. The cat was icteric with severe hyperbilirubinemia but no hematocrit changes. Severe obtundation and lateral recumbency progressed to tetraparesis and loss of proprioception in all four limbs, and a cerebellar or brainstem lesion was suspected. Post-mortem examination revealed suppurative cholangiohepatitis and acute neuronal necrosis in the nuclei of the brainstem and cerebellum, consistent with bilirubin encephalopathy. This is the first known occurrence of cholangiohepatitis and bilirubin encephalopathy in an adult cat with chronic hemolytic anemia. Although rare, bilirubin encephalopathy should be considered as a possible sequela to hyperbilirubinemia in adult patients. It remains unknown whether increased OF was related to the cholangiohepatopathy.",,"['Contreras, Elena T.', 'Giger, Urs', 'Malmberg, Jennifer L.', 'Quimby, Jessica M.', 'Schaffer, Paula A.']",,,,
,PMC,Egg Yolk IgY Antibodies: a Therapeutic Intervention Against Group A Rotavirus in Calves,http://dx.doi.org/10.1016/j.rvsc.2015.09.005,PMC4684595,,,"Bovine group A rotavirus (RVA) is considered the major cause of diarrhea in intensively reared neonatal calves. Chicken egg yolk antibodies (IgY) are efficient in protecting neonatal calves from RVA diarrhea; however, it is unclear the value of this intervention in calves once diarrhea has appeared. The aim of the present study was to evaluate the application of RVA-specific IgY as a passive treatment in those cases. The experimental groups were: G1= RVA-specific IgY treatment; G2= no Ab treatment; and G3= colostrum deprived + no Ab treatment. IgY treatment significantly reduced virus shedding, diarrhea duration and severity compared to G2 and G3 calves. However, it caused a partial suppression of systemic Ab responses to RVA that could be associated with less severe diarrhea. The oral treatment with IgY for 7 days was associated with significantly higher antibody secreting cell responses in the calves compared with the other groups of animals.",,"['Vega, C.', 'Bok, M.', 'Saif, L.', 'Fernandez, F.', 'Parreño, V.']",,,,
,PMC,Nutritional Impact of Dietary Plasma Proteins in Animals Undergoing Experimental Challenge and Implications for Patients with Inflammatory Bowel Disorders: A Meta-analysis(1)(2),http://dx.doi.org/10.3945/an.114.007930,PMC4561828,,,"Studies administering plasma protein isolates (PPIs) to experimentally challenged animals have reported improvements in growth, food intake, and overall condition when compared with animals fed control diets, due in part to improvements in gut barrier function, normalization of cytokine signals, and support of enteric immune function. These and early clinical studies suggest that nutritional therapy with PPIs may similarly assist in restoring homeostasis to gut barrier function in humans experiencing mild or more acute enteropathic symptomatology such as irritable bowel syndrome and inflammatory bowel disease. This meta-analysis evaluated the ability of PPIs to promote weight gain and food intake in weanling animals, primarily piglets, after oral challenge with various enteric pathogens or bacterial toxins. MEDLINE, EMBASE, and PubMed were searched from 1980 through August 2012 for specified terms and keywords. Twenty-nine articles retrieved through this process were evaluated; 11 studies including 13 experiments were selected for inclusion in the analysis. The meta-analysis included descriptive analyses and methods for combining P values for the primary endpoint, average daily growth (ADG) at week 1, and secondary endpoints including ADG, average daily feed intake (ADFI), and gain to feed ratio (G:F) at weeks 1 and 2 and at the end of study. Primary and secondary endpoint analyses of growth (ADG, ADFI, and G:F) were significant (P < 0.01). The proinflammatory cytokines interleukin (IL) 1β, IL-6, and tumor necrosis factor α were significantly lower in animals fed dietary PPIs. Additional research in patients experiencing symptoms of enteropathy will further characterize the benefits of PPIs in clinical populations.",,"['Kuchibhatla, Ramana', 'Petschow, Bryon W', 'Odle, Jack', 'Weaver, Eric M']",,,,
,PMC,Under the microscope: From pathogens to probiotics and back,http://dx.doi.org/10.1080/21655979.2015.1089368,PMC4825842,,,"The review centers on the human gastrointestinal tract; focusing first on the bacterial stress responses needed to overcome the physiochemical defenses of the host, specifically how these stress survival strategies can be used as targets for alternative infection control strategies. The concluding section focuses on recent developments in molecular diagnostics; centring on the shifting paradigm from culture to molecular based diagnostics.",,"Sleator, Roy D",,,,
,PMC,Loss of galectin-3 decreases the number of immune cells in the subventricular zone and restores proliferation in a viral model of multiple sclerosis,http://dx.doi.org/10.1002/glia.22906,PMC4988318,,,"Multiple sclerosis (MS) frequently starts near the lateral ventricles, which are lined by subventricular zone (SVZ) progenitor cells that can migrate to lesions and contribute to repair. Since MS-induced inflammation may decrease SVZ proliferation and thus limit repair, we studied the role of galectin-3 (Gal-3), a pro-inflammatory protein. Gal-3 expression was increased in periventricular regions of human MS in post-mortem brain samples and was also upregulated in periventricular regions in a murine MS model, Theiler’s murine encephalomyelitis virus (TMEV) infection. Whereas TMEV increased SVZ chemokine (CCL2, CCL5, CCL8 and CXCL10) expression in wild type (WT) mice, this was inhibited in Gal-3(−/−) mice. Though numerous CD45+ immune cells entered the SVZ of WT mice after TMEV infection, their numbers were significantly diminished in Gal-3(−/−) mice. TMEV also reduced neuroblast and proliferative SVZ cell numbers in WT mice but this was restored in Gal-3(−/−) mice and was correlated with increased numbers of doublecortin+ neuroblasts in the corpus callosum. In summary, our data showed that loss of Gal-3 blocked chemokine expression, reduced immune cell migration into the SVZ, reestablished SVZ proliferation and increased the number of progenitors in the corpus callosum. These results suggest Gal-3 plays a central role in modulating the SVZ neurogenic niche’s response to this model of MS.",,"['James, Rachel E.', 'Hillis, James', 'Adorján, István', 'Gration, Betty', 'Mundim, Mayara V.', 'Iqbal, Asif J.', 'Majumdar, Moon-Moon', 'Yates, Richard L.', 'Richards, Maureen M.H.', 'Goings, Gwendolyn E.', 'DeLuca, Gabriele C.', 'Greaves, David R.', 'Miller, Stephen D.', 'Szele, Francis G.']",,,,
,PMC,Modeling Epidemics Spreading on Social Contact Networks,http://dx.doi.org/10.1109/TETC.2015.2398353,PMC5051690,,,"Social contact networks and the way people interact with each other are the key factors that impact on epidemics spreading. However, it is challenging to model the behavior of epidemics based on social contact networks due to their high dynamics. Traditional models such as susceptible-infected-recovered (SIR) model ignore the crowding or protection effect and thus has some unrealistic assumption. In this paper, we consider the crowding or protection effect and develop a novel model called improved SIR model. Then, we use both deterministic and stochastic models to characterize the dynamics of epidemics on social contact networks. The results from both simulations and real data set conclude that the epidemics are more likely to outbreak on social contact networks with higher average degree. We also present some potential immunization strategies, such as random set immunization, dominating set immunization, and high degree set immunization to further prove the conclusion.",,"['ZHANG, ZHAOYANG', 'WANG, HONGGANG', 'WANG, CHONGGANG', 'FANG, HUA']",,,,
,PMC,Stability engineering of anti-EGFR scFv antibodies by rational design of a lambda-to-kappa swap of the V(L) framework using a structure-guided approach,http://dx.doi.org/10.1080/19420862.2015.1088618,PMC4966335,,,"Phage-display technology facilitates rapid selection of antigen-specific single-chain variable fragment (scFv) antibodies from large recombinant libraries. ScFv antibodies, composed of a V(H) and V(L) domain, are readily engineered into multimeric formats for the development of diagnostics and targeted therapies. However, the recombinant nature of the selection strategy can result in V(H) and V(L) domains with sub-optimal biophysical properties, such as reduced thermodynamic stability and enhanced aggregation propensity, which lead to poor production and limited application. We found that the C10 anti-epidermal growth factor receptor (EGFR) scFv, and its affinity mutant, P2224, exhibit weak production from E. coli. Interestingly, these scFv contain a fusion of lambda3 and lambda1 V-region (LV3 and LV1) genes, most likely the result of a PCR aberration during library construction. To enhance the biophysical properties of these scFvs, we utilized a structure-based approach to replace and redesign the pre-existing framework of the V(L) domain to one that best pairs with the existing V(H). We describe a method to exchange lambda sequences with a more stable kappa3 framework (KV3) within the V(L) domain that incorporates the original lambda DE-loop. The resulting scFvs, C10KV3_LV1DE and P2224KV3_LV1DE, are more thermodynamically stable and easier to produce from bacterial culture. Additionally, C10KV3_LV1DE and P2224KV3_LV1DE retain binding affinity to EGFR, suggesting that such a dramatic framework swap does not significantly affect scFv binding. We provide here a novel strategy for redesigning the light chain of problematic scFvs to enhance their stability and therapeutic applicability.",,"['Lehmann, Andreas', 'Wixted, Josephine H F', 'Shapovalov, Maxim V', 'Roder, Heinrich', 'Dunbrack, Roland L', 'Robinson, Matthew K']",,,,
,PMC,Why infectious disease research needs community ecology,http://dx.doi.org/10.1126/science.1259504,PMC4863701,,,"Infectious diseases often emerge from interactions among multiple species and across nested levels of biological organization. Threats as diverse as Ebola virus, human malaria, and bat white-nose syndrome illustrate the need for a mechanistic understanding of the ecological interactions underlying emerging infections. We describe how recent advances in community ecology can be adopted to address contemporary challenges in disease research. These analytical tools can identify the factors governing complex assemblages of multiple hosts, parasites, and vectors, and reveal how processes link across scales from individual hosts to regions. They can also determine the drivers of heterogeneities among individuals, species, and regions to aid targeting of control strategies. We provide examples where these principles have enhanced disease management and illustrate how they can be further extended.",,"['Johnson, Pieter T. J.', 'de Roode, Jacobus C.', 'Fenton, Andy']",,,,
,PMC,Therapeutic Applications of Curcumin Nanoformulations,http://dx.doi.org/10.1208/s12248-015-9811-z,PMC4627456,,,"Curcumin (diferuloylmethane) is a bioactive and major phenolic component of turmeric derived from the rhizomes of curcuma longa linn. For centuries, curcumin has exhibited excellent therapeutic benefits in various diseases. Owing to its anti-oxidant and anti-inflammatory properties, curcumin plays a significant beneficial and pleiotropic regulatory role in various pathological conditions including cancer, cardiovascular disease, Alzheimer’s disease, inflammatory disorders, neurological disorders, and so on. Despite such phenomenal advances in medicinal applications, the clinical implication of native curcumin is hindered due to low solubility, physico-chemical instability, poor bioavailability, rapid metabolism, and poor pharmacokinetics. However, these issues can be overcome by utilizing an efficient delivery system. Active scientific research was initiated in 2005 to improve curcumin’s pharmacokinetics, systemic bioavailability, and biological activity by encapsulating or by loading curcumin into nanoform(s) (nanoformulations). A significant number of nanoformulations exist that can be translated toward medicinal use upon successful completion of pre-clinical and human clinical trials. Considering this perspective, current review provides an overview of an efficient curcumin nanoformulation for a targeted therapeutic option for various human diseases. In this review article, we discuss the clinical evidence, current status, and future opportunities of curcumin nanoformulation(s) in the field of medicine. In addition, this review presents a concise summary of the actions required to develop curcumin nanoformulations as pharmaceutical or nutraceutical candidates.",,"['Yallapu, Murali M.', 'Nagesh, Prashanth K. Bhusetty', 'Jaggi, Meena', 'Chauhan, Subhash C.']",,,,
,PMC,Big Data and the Global Public Health Intelligence Network (GPHIN),http://dx.doi.org/10.14745/ccdr.v41i09a02,PMC5933838,,,"BACKGROUND: Globalization and the potential for rapid spread of emerging infectious diseases have heightened the need for ongoing surveillance and early detection. The Global Public Health Intelligence Network (GPHIN) was established to increase situational awareness and capacity for the early detection of emerging public health events. OBJECTIVE: To describe how the GPHIN has used Big Data as an effective early detection technique for infectious disease outbreaks worldwide and to identify potential future directions for the GPHIN. FINDINGS: Every day the GPHIN analyzes over more than 20,000 online news reports (over 30,000 sources) in nine languages worldwide. A web-based program aggregates data based on an algorithm that provides potential signals of emerging public health events which are then reviewed by a multilingual, multidisciplinary team. An alert is sent out if a potential risk is identified. This process proved useful during the Severe Acute Respiratory Syndrome (SARS) outbreak and was adopted shortly after by a number of countries to meet new International Health Regulations that require each country to have the capacity for early detection and reporting. The GPHIN identified the early SARS outbreak in China, was credited with the first alert on MERS-CoV and has played a significant role in the monitoring of the Ebola outbreak in West Africa. Future developments are being considered to advance the GPHIN’s capacity in light of other Big Data sources such as social media and its analytical capacity in terms of algorithm development. CONCLUSION: The GPHIN’s early adoption of Big Data has increased global capacity to detect international infectious disease outbreaks and other public health events. Integration of additional Big Data sources and advances in analytical capacity could further strengthen the GPHIN’s capability for timely detection and early warning.",,"['Dion, M', 'AbdelMalik, P', 'Mawudeku, A']",,,,
,PMC,Evaluation of a national pharmacy‐based syndromic surveillance system,http://dx.doi.org/10.14745/ccdr.v41i09a01,PMC5864265,,,"BACKGROUND: Traditional public health surveillance provides accurate information but is typically not timely. New early warning systems leveraging timely electronic data are emerging, but the public health value of such systems is still largely unknown. OBJECTIVE: To assess the timeliness and accuracy of pharmacy sales data for both respiratory and gastrointestinal infections and to determine its utility in supporting the surveillance of gastrointestinal illness. METHODS: To assess timeliness, a prospective and retrospective analysis of data feeds was used to compare the chronological characteristics of each data stream. To assess accuracy, Ontario antiviral prescriptions were compared to confirmed cases of influenza and cases of influenza-like-illness (ILI) from August 2009 to January 2015 and Nova Scotia sales of respiratory over-the-counter products (OTC) were compared to laboratory reports of respiratory pathogen detections from January 2014 to March 2015. Enteric outbreak data (2011-2014) from Nova Scotia were compared to sales of gastrointestinal products for the same time period. To assess utility, pharmacy sales of gastrointestinal products were monitored across Canada to detect unusual increases and reports were disseminated to the provinces and territories once a week between December 2014 and March 2015 and then a follow-up evaluation survey of stakeholders was conducted. RESULTS: Ontario prescriptions of antivirals between 2009 and 2015 correlated closely with the onset dates and magnitude of confirmed influenza cases. Nova Scotia sales of respiratory OTC products correlated with increases in non-influenza respiratory pathogens in the community. There were no definitive correlations identified between the occurrence of enteric outbreaks and the sales of gastrointestinal OTCs in Nova Scotia. Evaluation of national monitoring showed no significant increases in sales of gastrointestinal products that could be linked to outbreaks that included more than one province or territory. CONCLUSION: Monitoring of pharmacy-based drug prescriptions and OTC sales can provide a timely and accurate complement to traditional respiratory public health surveillance activities but initial evaluation did not show that tracking gastrointestinal-related OTCs were of value in identifying an enteric disease outbreak in more than one province or territory during the study period.",,"['Muchaal, PK', 'Parker, S', 'Meganath, K', 'Landry, L', 'Aramini, J']",,,,
,PMC,Big Data is changing the battle against infectious diseases,http://dx.doi.org/10.14745/ccdr.v41i09a03,PMC5864264,,,"Big Data has traditionally been associated with computer geeks and commercial enterprises, but it has become entrenched in many scientific disciplines including the prevention and control of infectious diseases. The use of Big Data has allowed disease trends to be identified and outbreak origins to be tracked and even predicted. Big Data is not getting smaller. The challenges we face are to hone our analytical capacity to address the huge “signal-to-noise” ratio with adequate computing power and multidisciplinary teams that can handle ever-increasing amounts of data. Big Data will also create the opportunity for future applications of bespoke (or personalized) treatment.",,"Links, MG",,,,
,PMC,"Over-expression, purification, and confirmation of Bacillus anthracis transcriptional regulator NprR",http://dx.doi.org/10.1016/j.pep.2015.08.030,PMC4853309,,,"Quorum sensing (QS) has been recognized as an important biological phenomenon in which bacterial cells communicate and coordinate their gene expression and cellular processes with respect to population density. Bacillus anthracis is the etiological agent of fatal pulmonary anthrax infections, and the NprR/NprX QS system may be involved in its pathogenesis. NprR, renamed as aqsR for anthrax quorum sensing Regulator, is a transcriptional regulator that may control the expression of genes required for proliferation and survival. Currently, there is no protocol reported to over-express and purify B. anthracis AqsR. In this study, we describe cloning, purification, and confirmation of functional full-length B. anthracis AqsR protein. The AqsR gene was cloned into the pQE-30 vector with an HRV 3C protease recognition site between AqsR and the N-terminal His(6)-tag in order to yield near native AqsR after the His-tag cleavage, leaving only two additional amino acid residues at the N-terminus.",,"['Rice, Amy J.', 'Woo, Jerry K.', 'Khan, Attiya', 'Szypulinski, Michael Z.', 'Johnson, Michael E.', 'Lee, Hyunwoo', 'Lee, Hyun']",,,,
,PMC,Intratracheal exposure of common marmosets to MERS-CoV Jordan-n3/2012 or MERS-CoV EMC/2012 isolates does not result in lethal disease,http://dx.doi.org/10.1016/j.virol.2015.07.013,PMC5001852,,,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a threat to human health in the Middle East. Development of countermeasures is ongoing; however, an animal model that faithfully recapitulates human disease has yet to be defined. A recent study indicated that inoculation of common marmosets resulted in inconsistent lethality. Based on these data we sought to compare two isolates of MERS-CoV. We followed disease progression in common marmosets after intratracheal exposure with: MERS-CoV-EMC/2012, MERS-CoV-Jordan-n3/2012, media, or inactivated virus. Our data suggest that common marmosets developed a mild to moderate non-lethal respiratory disease, which was quantifiable by computed tomography (CT), with limited other clinical signs. Based on CT data, clinical data, and virological data, MERS-CoV inoculation of common marmosets results in mild to moderate clinical signs of disease that are likely due to manipulations of the marmoset rather than as a result of robust viral replication.",,"['Johnson, Reed F.', 'Via, Laura E.', 'Kumar, Mia R.', 'Cornish, Joseph P.', 'Yellayi, Srikanth', 'Huzella, Louis', 'Postnikova, Elena', 'Oberlander, Nicholas', 'Bartos, Christopher', 'Ork, Britini L.', 'Mazur, Steven', 'Allan, Cindy', 'Holbrook, Michael R.', 'Solomon, Jeffrey', 'Johnson, Joshua C.', 'Pickel, James', 'Hensley, Lisa E.', 'Jahrling, Peter B.']",,,,
,PMC,Herbal plants and plant preparations as remedial approach for viral diseases,http://dx.doi.org/10.1007/s13337-015-0276-6,PMC4663710,,,"Herbal plants, plant preparations and phytoconstituents have proved useful in attenuating infectious conditions and were the only remedies available, till the advent of antibiotics (many being of plant origin themselves). Among infectious diseases, viral diseases in particular, remain the leading cause of death in humans globally. A variety of phytoconstituents derived from medicinal herbs have been extensively studied for antiviral activity. Based on this rationale, an online search was performed, which helped to identify a large number of plant species harboring antiviral molecules. These herbal sources have been reported individually or in combinations across a large number of citations studied. Activities against rabies virus, Human immunodeficiency virus, Chandipura virus, Japanese Encephalitis Virus, Enterovirus, Influenza A/H1N1 and other influenza viruses were discovered during the literature search. This review includes all such plant species exhibiting antiviral properties. The review also encompasses composition and methodologies of preparing various antiviral formulations around the globe. An elaborate section on the formulations filed for patent registration, along with non-patented formulations, has also been included in this article. To conclude, herbal sources provide researchers enormous scope to explore and bring out viable alternatives against viral diseases, considering non-availability of suitable drug candidates and increasing resistance to existing drug molecules for many emerging and re-emerging viral diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13337-015-0276-6) contains supplementary material, which is available to authorized users.",,"['Ganjhu, Rajesh Kumar', 'Mudgal, Piya Paul', 'Maity, Hindol', 'Dowarha, Deepu', 'Devadiga, Santhosha', 'Nag, Snehlata', 'Arunkumar, Govindakarnavar']",,,,
,PMC,Ebola Virus Disease: Rapid Diagnosis and Timely Case Reporting are Critical to the Early Response for Outbreak Control,http://dx.doi.org/10.4269/ajtmh.15-0229,PMC4559677,,,"Ebola virus disease (EVD) is a life-threatening zoonosis caused by infection with the Ebola virus. Since the first reported EVD outbreak in the Democratic Republic of the Congo, several small outbreaks have been reported in central Africa with about 2,400 cases occurring between 1976 and 2013. The 2013–2015 EVD outbreak in west Africa is the first documented outbreak in this region and the largest ever with over 27,000 cases and more than 11,000 deaths. Although EVD transmission rates have recently decreased in west Africa, this crisis continues to threaten global health and security, particularly since infected travelers could spread EVD to other resource-limited areas of the world. Because vaccines and drugs are not yet licensed for EVD, outbreak control is dependent on the use of non-pharmaceutical interventions (e.g., infection control practices, isolation of EVD cases, contact tracing with follow-up and quarantine, sanitary burial, health education). However, delays in diagnosing and reporting EVD cases in less accessible rural areas continue to hamper control efforts. New advances in rapid diagnostics for identifying presumptive EVD cases and in mobile-based technologies for communicating critical health-related information should facilitate deployment of an early response to prevent the amplification of sporadic EVD cases into large-scale outbreaks.",,"Stamm, Lola V.",,,,
,PMC,The ns12.9 Accessory Protein of Human Coronavirus OC43 Is a Viroporin Involved in Virion Morphogenesis and Pathogenesis,http://dx.doi.org/10.1128/JVI.01986-15,PMC4645656,,,"An accessory gene between the S and E gene loci is contained in all coronaviruses (CoVs), and its function has been studied in some coronaviruses. This gene locus in human coronavirus OC43 (HCoV-OC43) encodes the ns12.9 accessory protein; however, its function during viral infection remains unknown. Here, we engineered a recombinant mutant virus lacking the ns12.9 protein (HCoV-OC43-Δns12.9) to characterize the contributions of ns12.9 in HCoV-OC43 replication. The ns12.9 accessory protein is a transmembrane protein and forms ion channels in both Xenopus oocytes and yeast through homo-oligomerization, suggesting that ns12.9 is a newly recognized viroporin. HCoV-OC43-Δns12.9 presented at least 10-fold reduction of viral titer in vitro and in vivo. Intriguingly, exogenous ns12.9 and heterologous viroporins with ion channel activity could compensate for the production of HCoV-OC43-Δns12.9, indicating that the ion channel activity of ns12.9 plays a significant role in the production of infectious virions. Systematic dissection of single-cycle replication revealed that ns12.9 protein had no measurable effect on virus entry, subgenomic mRNA (sgmRNA) synthesis, and protein expression. Further characterization revealed that HCoV-OC43-Δns12.9 was less efficient in virion morphogenesis than recombinant wild-type virus (HCoV-OC43-WT). Moreover, reduced viral replication, inflammatory response, and virulence in HCoV-OC43-Δns12.9-infected mice were observed compared to the levels for HCoV-OC43-WT-infected mice. Taken together, our results demonstrated that the ns12.9 accessory protein functions as a viroporin and is involved in virion morphogenesis and the pathogenesis of HCoV-OC43 infection. IMPORTANCE HCoV-OC43 was isolated in the 1960s and is a major agent of the common cold. The functions of HCoV-OC43 structural proteins have been well studied, but few studies have focused on its accessory proteins. In the present study, we demonstrated that the ns12.9 protein is a newly recognized viroporin, and the ns12.9 gene knockout virus (HCoV-OC43-Δns12.9) presents a growth defect in vitro and in vivo. We identified the important functions of the ns12.9 viroporin in virion morphogenesis during HCoV-OC43 infection. Furthermore, mice infected with HCoV-OC43-Δns12.9 exhibited reduced inflammation and virulence accompanied by a lower titer in the brain than that of wild-type-infected mice, suggesting the ns12.9 viroporin influences virus pathogenesis. Therefore, our findings revealed that the ns12.9 viroporin facilitates virion morphogenesis to enhance viral production, and these results provided a deeper understanding of HCoV-OC43 pathogenesis.",,"['Zhang, Ronghua', 'Wang, Kai', 'Ping, Xianqiang', 'Yu, Wenjing', 'Qian, Zhikang', 'Xiong, Sidong', 'Sun, Bing']",,,,
,PMC,"Knowledge, Attitude and practices regarding vector-borne diseases in Western Jamaica",http://dx.doi.org/10.1016/j.aogh.2015.08.013,PMC4818946,,,"BACKGROUND: Outbreaks of vector-borne diseases such as dengue, and malaria can overwhelm health systems in resource-poor countries. Environmental management strategies that reduce/eliminate vector breeding sites combined with improved personal prevention strategies can help to significantly reduce transmission of these infections. OBJECTIVE: This study was conducted to assess the knowledge, attitudes and practices (KAPs) of residents in Western Jamaica regarding control of mosquito vectors and protection from mosquito bites. METHODS: A cross-sectional study was conducted between May and August 2010 among patients or family members of patients waiting to be seen at hospitals in Western Jamaica. Participants completed an interviewer-administered questionnaire on sociodemographic factors and KAPs regarding vector-borne diseases. KAP scores were calculated and categorized as high or low based on number of correct/positive responses. Logistic regression analyses were conducted to identify predictors of KAP and linear regression analysis conducted to determine if knowledge and attitude scores predicted practice scores. RESULTS: Three-hundred and sixty-one people (85 males and 276 females) participated in the study. Most participants (87%) scored low on knowledge and practice items (78%). Conversely, 78% scored high on attitudes items. By multivariate logistic regression, housewives were 82% less likely to have high attitude scores than laborers, and homeowners were 65% less likely to have high attitude scores than renters. Participants from households with 1–2 children were 3.4 times more likely to have high attitude scores compared to those from households with no children. Participants from households ≥5 people were 65% less likely to have high practice scores compared to those from households with <5. By multivariable linear regression knowledge and attitude scores were significant predictors of practice score. CONCLUSION: The study revealed poor knowledge of vector-borne diseases and poor prevention practices among participants. It identified specific groups that can be targeted with vector-control and personal protection interventions to decrease transmission of the infections.",,"['Alobuia, Wilson M', 'Missikpode, Celestin', 'Aung, Maung', 'Jolly, Pauline E']",,,,
,PMC,Replication-Competent Influenza Virus and Respiratory Syncytial Virus Luciferase Reporter Strains Engineered for Co-Infections Identify Antiviral Compounds in Combination Screens,http://dx.doi.org/10.1021/acs.biochem.5b00623,PMC4719150,,,"Myxoviruses such as influenza A virus (IAV) and respiratory syncytial virus (RSV) are major human pathogens, mandating the development of novel therapeutics. To establish a high-throughput screening protocol for the simultaneous identification of pathogen- and host-targeted hit candidates against either or both pathogens, we have attempted coinfection of cells with IAV and RSV. However, viral replication kinetics were incompatible, RSV signal window was low, and an IAV-driven minireplicon reporter assay used in initial screens narrowed the host cell range and restricted to single-cycle infections. To overcome these limitations, we developed an RSV strain carrying firefly luciferase fused to an innovative universal small-molecule assisted shut-off domain, which boosted assay signal window, and a hyperactive fusion protein that synchronized IAV and RSV reporter expression kinetics and suppresses the identification of RSV entry inhibitors sensitive to a recently reported RSV pan-resistance mechanism. Combined with a replication-competent recombinant IAV strain harboring nano-luciferase, the assay performed well on a human respiratory cell line and supports multi-cycle infections. Miniaturized to 384-well format, the protocol was validated through screening of a set of the NIH Clinical Collection (NCC) in quadruplicate. These test screens demonstrated favorable assay parameters and reproducibility. Application to a LOPAC library of bioactive compounds in a proof-of-concept campaign detected licensed anti-myxovirus therapeutics, ribavirin and the neuraminidase inhibitor zanamivir, and identified two unexpected RSV-specific hit candidates, Fenretinide and the opioid receptor antagonist BNTX-7. Hits were evaluated in direct and orthogonal dose-response counterscreens using a standard recRSV reporter strain expressing renilla luciferase.",,"['Yan, Dan', 'Weisshaar, Marco', 'Lamb, Kristen', 'Chung, Hokyung K', 'Lin, Michael Z', 'Plemper, Richard K']",,,,
,PMC,Incubation Period Duration and Severity of Clinical Disease Following Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1097/EDE.0000000000000339,PMC4889459,,,"BACKGROUND: Few previous studies have investigated the association between the severity of an infectious disease and the length of incubation period. METHODS: We estimated the association between the length of the incubation period and the severity of infection with the severe acute respiratory syndrome (SARS) coronavirus, using data from the epidemic in 2003 in Hong Kong. RESULTS: We estimated the incubation period of SARS based on a subset of patients with available data on exposure periods and a separate subset of patients in a putative common source outbreak, and we found significant associations between shorter incubation period and greater severity in both groups after adjusting for potential confounders. CONCLUSIONS: Our findings suggest that patients with a shorter incubation period proceeded to have more severe disease. Further studies are needed to investigate potential biological mechanisms for this association.",,"['Virlogeux, Victor', 'Fang, Vicky J.', 'Wu, Joseph T.', 'Ho, Lai-Ming', 'Malik Peiris, J. S.', 'Leung, Gabriel M.', 'Cowling, Benjamin J.']",,,,
,PMC,Critical care medicine for emerging Middle East respiratory syndrome: Which point to be considered?,http://dx.doi.org/10.4103/0972-5229.164802,PMC4578197,26430339,CC BY-NC-SA,"The Middle East respiratory syndrome (MERS) is a new emerging respiratory tract infection. This coronavirus infection is firstly reported from the Middle East, and it becomes threat for the global public health at present due to its existence in a remote area such as USA and Korea. The concern on the management of the patients is very important. Since most of the patients can develop severe respiratory illness and critical care management is needed, the issue on critical care for MERS is the topic to be discussed in critical medicine.",2015 Sep,"Wiwanitkit, Viroj",Indian J Crit Care Med,,,
,PMC,Brucella melitensis and Mycobacterium tuberculosis depict overlapping gene expression patterns induced in infected THP-1 macrophages,,PMC4782677,,,"Pathogens infecting mammalian cells have developed various strategies to suppress and evade their hosts’ defensive mechanisms. In this line, the intracellular bacteria that are able to survive and propagate within their host cells must have developed strategies to avert their host’s killing attitude. Studying the interface of host-pathogen confrontation can provide valuable information for defining therapeutic approaches. Brucellosis, caused by the Brucella strains, is a zoonotic bacterial disease that affects thousands of humans and animals around the world inflicting discomfort and huge economic losses. Similar to many other intracellular dwelling bacteria, infections caused by Brucella are difficult to treat, and hence any attempt at identifying new and common therapeutic targets would prove beneficial for the purpose of curing infections caused by the intracellular bacteria. In THP-1 macrophage infected with Brucella melitensis we studied the expression levels of four host’s genes, i.e. EMP2, ST8SIA4, HCP5 and FRMD5 known to be involved in pathogenesis of Mycobacterium tuberculosis. Our data showed that at this molecular level, except for FRMD5 that was downregulated, the other three genes were upregulated by B. melitensis. Brucella melitensis and M. tuberculosis go through similar intracellular processes and interestingly two of the investigated genes, i.e. EMP2 and ST4SIA8 were upregulated in THP-1 cell infected with B. melitensis similar to that reported for THP-1 cells infected with M. tuberculosis. At the host-pathogen interaction interface, this study depicts overlapping changes for different bacteria with common survival strategies; a fact that implies designing therapeutic approaches based on common targets may be possible.",,"['Masoudian, M', 'Derakhshandeh, A', 'Ghahramani Seno, M. M']",,,,
,PMC,Relationship between Plasma Albumin Concentration and Plasma Volume in 5 Inbred Rat Strains,,PMC4587612,,,"Using the Evans Blue procedure, we previously found strain-related differences in plasma volumes in 5 inbred rat strains. Because albumin binds strongly with Evans blue, this protein is important in the Evans blue method of plasma volume determination. Therefore, we speculated that interstrain differences in plasma albumin concentration (PAC) could distort calculated plasma volumes. To address this concern, we used ELISA techniques to measure PAC in these inbred rat strains. In study A, the blood volume was measured by using Evans blue dye, and albumin was measured at the start of hemorrhage. In study B, blood volume was not measured, and albumin was measured twice, near the start and end of hemorrhage (approximately 14 min apart). Neither study revealed any interstrain differences in PAC, which decreased after hemorrhage in all 5 strains. No correlation was found between PAC and plasma volume, survival time, blood lactate, or blood base excess. Percentage changes in PAC during hemorrhage were greater in salt-sensitive compared with Lewis rats. Moreover, these percentage changes were associated with survival time in Fawn hooded hypertensive rats. Our data show that the plasma volumes we measured previously were not misrepresented due to variations in PAC.",,"['Rose, Rajiv', 'Klemcke, Harold G']",,,,
,PMC,What is the pain source? A case report of a patient with low back pain and bilateral hip osteonecrosis,,PMC4593036,,,BACKGROUND: Low back pain is a common symptom arising from many possible sources and includes the possibility of the contribution of remote pathology. This report describes a patient with bilateral osteonecrosis of the femoral heads presenting with a primary symptom of low back pain. CASE PRESENTATION: A 37-year-old male presented for evaluation of dominant pain that existed for approximately 6–12 months and was located in the right low back. Milder pain was also reported in the right hip. Low back and hip pain were both aggravated by weight-bearing activities. An evidence-based diagnostic evaluation revealed little indication for a primary pain source originating from low back structures. Radiographs revealed bilateral osteonecrosis with evidence of left femoral head collapse. CONCLUSION: Hip osteonecrosis may have contributed to an atypical presentation of low back pain due to aberrant localization of pain and/or combined with altered biomechanical loading of musculoskeletal structures.,,"['Minkalis, Amy L.', 'Vining, Robert D.']",,,,
,PMC,Connecting within and between-hosts dynamics in the influenza infection-staged epidemiological models with behavior change,http://dx.doi.org/10.1166/jcsmd.2015.1082,PMC5654582,,,"Influenza viruses are a major public health problem worldwide. Although influenza has been extensively researched, there are still many aspects that are not fully understood such as the effects of within and between-hosts dynamics and their impact on behavior change. Here, we develop mathematical models with multiple infection stages and estimate parameters based on within-host data to investigate the impact of behavior change on influenza dynamics. We divide the infected population into three and four groups based on the age of the infection, which corresponds to viral load shedding. We consider within-host data on viral shedding to estimate the length and force of infection of the different infectivity stages. Our results show that behavior changes, due to exogenous events (e.g., media coverage) and disease symptoms, are effective in delaying and lowering an epidemic peak. We show that the dynamics of viral shedding and symptoms, during the infection, are key features when considering epidemic prevention strategies. This study improves our understanding of the spread of influenza virus infection in the population and provides information about the impact of emergent behavior and its connection to the within and between-hosts dynamics.",,"['Pawelek, Kasia A.', 'Salmeron, Cristian', 'Del Valle, Sara']",,,,
,PMC,Exploring the virome of diseased horses,http://dx.doi.org/10.1099/vir.0.000199,PMC4635498,,,"Metagenomics was used to characterize viral genomes in clinical specimens of horses with various organ-specific diseases of unknown aetiology. A novel parvovirus as well as a previously described hepacivirus closely related to human hepatitis C virus and equid herpesvirus 2 were identified in the cerebrospinal fluid of horses with neurological signs. Four co-infecting picobirnaviruses, including an unusual genome with fused RNA segments, and a divergent anellovirus were found in the plasma of two febrile horses. A novel cyclovirus genome was characterized from the nasal secretion of another febrile animal. Lastly, a small circular DNA genome with a Rep gene, from a virus we called kirkovirus, was identified in the liver and spleen of a horse with fatal idiopathic hepatopathy. This study expands the number of viruses found in horses, and characterizes their genomes to assist future epidemiological studies of their transmission and potential association with various equine diseases.",,"['Li, Linlin', 'Giannitti, Federico', 'Low, Jason', 'Keyes, Casey', 'Ullmann, Leila S.', 'Deng, Xutao', 'Aleman, Monica', 'Pesavento, Patricia A.', 'Pusterla, Nicola', 'Delwart, Eric']",,,,
,PMC,Alphavirus RNA synthesis and non-structural protein functions,http://dx.doi.org/10.1099/jgv.0.000249,PMC4635493,,,"The members of the genus Alphavirus are positive-sense RNA viruses, which are predominantly transmitted to vertebrates by a mosquito vector. Alphavirus disease in humans can be severely debilitating, and depending on the particular viral species, infection may result in encephalitis and possibly death. In recent years, alphaviruses have received significant attention from public health authorities as a consequence of the dramatic emergence of chikungunya virus in the Indian Ocean islands and the Caribbean. Currently, no safe, approved or effective vaccine or antiviral intervention exists for human alphavirus infection. The molecular biology of alphavirus RNA synthesis has been well studied in a few species of the genus and represents a general target for antiviral drug development. This review describes what is currently understood about the regulation of alphavirus RNA synthesis, the roles of the viral non-structural proteins in this process and the functions of cis-acting RNA elements in replication, and points to open questions within the field.",,"['Rupp, Jonathan C.', 'Sokoloski, Kevin J.', 'Gebhart, Natasha N.', 'Hardy, Richard W.']",,,,
,PMC,Vaccination With a Highly Attenuated Recombinant Vesicular Stomatitis Virus Vector Protects Against Challenge With a Lethal Dose of Ebola Virus,http://dx.doi.org/10.1093/infdis/jiv316,PMC4564554,,,"Previously, recombinant vesicular stomatitis virus (rVSV) pseudotypes expressing Ebolavirus glycoproteins (GPs) in place of the VSV G protein demonstrated protection of nonhuman primates from lethal homologous Ebolavirus challenge. Those pseudotype vectors contained no additional attenuating mutations in the rVSV genome. Here we describe rVSV vectors containing a full complement of VSV genes and expressing the Ebola virus (EBOV) GP from an additional transcription unit. These rVSV vectors contain the same combination of attenuating mutations used previously in the clinical development pathway of an rVSV/human immunodeficiency virus type 1 vaccine. One of these rVSV vectors (N4CT1-EBOVGP1), which expresses membrane-anchored EBOV GP from the first position in the genome (GP1), elicited a balanced cellular and humoral GP-specific immune response in mice. Guinea pigs immunized with a single dose of this vector were protected from any signs of disease following lethal EBOV challenge, while control animals died in 7–9 days. Subsequently, N4CT1-EBOVGP1 demonstrated complete, single-dose protection of 2 macaques following lethal EBOV challenge. A single sham-vaccinated macaque died from disease due to EBOV infection. These results demonstrate that highly attenuated rVSV vectors expressing EBOV GP may provide safer alternatives to current EBOV vaccines.",,"['Matassov, Demetrius', 'Marzi, Andrea', 'Latham, Terri', 'Xu, Rong', 'Ota-Setlik, Ayuko', 'Feldmann, Friederike', 'Geisbert, Joan B.', 'Mire, Chad E.', 'Hamm, Stefan', 'Nowak, Becky', 'Egan, Michael A.', 'Geisbert, Thomas W.', 'Eldridge, John H.', 'Feldmann, Heinz', 'Clarke, David K.']",,,,
,PMC,Characterization of a Bivalent Vaccine Capable of Inducing Protection Against Both Ebola and Cross-clade H5N1 Influenza in Mice,http://dx.doi.org/10.1093/infdis/jiv257,PMC4564552,,,"Background. Ebola virus (EBOV) is a lethal pathogen that causes up to 90% mortality in humans, whereas H5N1 avian influenza has a 60% fatality rate. Both viruses are considered pandemic threats. The objective was to evaluate the protective efficacy of a bivalent, recombinant vesicular stomatitis virus vaccine expressing both the A/Hanoi/30408/2005 H5N1 hemagglutinin and the EBOV glycoprotein (VSVΔG-HA-ZGP) in a lethal mouse model of infection. Methods. Mice were vaccinated 28 days before or 30 minutes after a lethal challenge with mouse-adapted EBOV or selected H5N1 influenza viruses from clades 0, 1, and 2. Animals were monitored for weight loss and survival, in addition to humoral and cell-mediated responses after immunization. Results. A single VSVΔG-HA-ZGP injection was efficacious when administered 28 days before a homologous H5N1 and/or mouse-adapted EBOV challenge, as well as a heterologous H5N1 challenge. Postexposure protection was only observed in vaccinated animals challenged with homologous H5N1 and/or mouse-adapted EBOV. Analysis of the adaptive immune response postvaccination revealed robust specific T- and B-cell responses, including a potent hemagglutinin inhibition antibody response against all H5N1 strains tested. Conclusions. The results highlight the ability of vesicular stomatitis virus–vectored vaccines to rapidly confer protection against 2 unrelated pathogens and stimulate cross-protection against H5N1 influenza viruses.",,"['Wong, Gary', 'Qiu, Xiangguo', 'Ebihara, Hideki', 'Feldmann, Heinz', 'Kobinger, Gary P.']",,,,
,PMC,Development and Characterization of Broadly Cross-reactive Monoclonal Antibodies Against All Known Ebolavirus Species,http://dx.doi.org/10.1093/infdis/jiv209,PMC4564547,,,"As of 25 March 2015, the largest recorded outbreak of Ebola virus infection is ongoing, with almost 25 000 cases and >10 000 deaths. There are 5 genetically and antigenically distinct species within the genus Ebolavirus. Limited cross-reactivity and protection is observed between these 5 Ebolavirus species, which complicates vaccine development. However, on the basis of sequence homology between the 5 Ebolavirus species, we hypothesize that conserved epitopes are present on the viral glycoprotein (GP), which can be targeted by antibodies. In the current study, a panel of mouse monoclonal antibodies was isolated and characterized using an enzyme-linked immunosorbent assay (ELISA) to determine cross-reactivity, avidity, and competition for epitope binding; Western blot analysis was also performed. Four monoclonal antibodies were identified by ELISA as cross-reacting with the GPs of all 5 Ebolavirus species. The identification of cross-reactive antibodies that bind the GPs of all known Ebolavirus species will give us important insight into the presence of conserved epitopes on the viral GP. These data will be crucial for the development of novel therapeutics and diagnostic assays.",,"['Hernandez, Humberto', 'Marceau, Caleb', 'Halliday, Hailey', 'Callison, Julie', 'Borisevich, Viktoriya', 'Escaffre, Olivier', 'Creech, Jeffrey', 'Feldmann, Heinz', 'Rockx, Barry']",,,,
,PMC,"Abstracts published at Infection Prevention 2015, Liverpool",http://dx.doi.org/10.1177/1757177415599501,PMC5074091,,,,,,,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.01963-15,PMC4577912,,,,,,,,,
,PMC,Policy Address(),,PMC4716959,,,,,"YOKOKURA, Yoshitake",,,,
,PMC,PharmGKB summary: peginterferon-α pathway,http://dx.doi.org/10.1097/FPC.0000000000000158,PMC4757589,,,,,"['Shuldiner, Scott R.', 'Gong, Li', 'Muir, Andrew J.', 'Altman, Russ B.', 'Klein, Teri E.']",,,,
,PMC,Therapeutic Interventions to Disrupt the Protein Synthetic Machinery in Melanoma,http://dx.doi.org/10.1111/pcmr.12391,PMC4716672,,,"Control of the protein synthetic machinery is deregulated in many cancers, including melanoma, in order to increase protein production. Tumor suppressors and oncogenes play key roles in protein synthesis from the transcription of rRNA and ribosome biogenesis to mRNA translation initiation and protein synthesis. Major signaling pathways are altered in melanoma to modulate the protein synthetic machinery thereby promoting tumor development. However, despite the importance of this process in melanoma development, involvement of the protein synthetic machinery in this cancer type is an underdeveloped area of study. Here, we review the coupling of melanoma development to deregulation of the protein synthetic machinery. We examine existing knowledge regarding RNA Polymerase I inhibition and mRNA translation focusing on their inhibition for therapeutic applications in melanoma. Furthermore, the contribution of amino acid biosynthesis and involvement of ribosomal proteins are also reviewed as future therapeutic strategies to target deregulated protein production in melanoma.",,"['Kardos, Gregory R.', 'Robertson, Gavin P.']",,,,
,PMC,Public Health Laboratories and the Affordable Care Act: What the New Health-Care System Means for Public Health Preparedness,,PMC4529839,,,,,"['Malcarney, Mary-Beth', 'Seiler, Naomi', 'Horton, Katie']",,,,
,PMC,Interferon Gamma Induces Protective Non-Canonical Signaling Pathways in Primary Neurons,http://dx.doi.org/10.1111/jnc.13250,PMC4809142,,,"The signal transduction molecule, Stat1, is critical for the expression of type I and II interferon (IFN)-responsive genes in most cells; however, we previously showed that primary hippocampal mouse neurons express low basal Stat1, with delayed and attenuated expression of IFN-responsive genes. Moreover, IFNγ-dependent resolution of a neurotropic viral challenge in permissive mice is Stat1-independent. Here, we show that exogenous INFγ has no deleterious impact on neuronal viability, and staurosporine-induced apoptosis in neurons is significantly blunted by the addition of INFγ, suggesting that INFγ confers a pro-survival signal in neurons. To identify the pathways induced by INFγ in neurons, the activation of alternative signal transducers associated with INFγ signaling was assessed. Rapid and pronounced activation of extracellular signal regulated kinase (Erk1/2) was observed in neurons, compared to a modest response in fibroblasts. Moreover, the absence of Stat1 in primary fibroblasts led to enhanced Erk activation following IFNγ addition, implying that the cell-specific availability of signal transducers can diversify the cellular response following IFN engagement.",,"[""O'Donnell, Lauren A."", 'Henkins, Kristen M.', 'Kulkarni, Apurva', 'Matullo, Christine M.', 'Balachandran, Siddharth', 'Pattisapu, Anil K.', 'Rall, Glenn F.']",,,,
,PMC,SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS E PROTEIN TRANSPORTS CALCIUM IONS AND ACTIVATES THE NLRP3 INFLAMMASOME,http://dx.doi.org/10.1016/j.virol.2015.08.010,PMC4619128,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein is a viroporin involved in virulence. E protein ion channel (IC) activity is specifically correlated with enhanced pulmonary damage, edema accumulation and death. IL-1β driven proinflammation is associated with those pathological signatures, however its link to IC activity remains unknown. In this report, we demonstrate that SARS-CoV E protein forms protein-lipid channels in ERGIC/Golgi membranes that are permeable to calcium ions, a highly relevant feature never reported before. Calcium ions together with pH modulated E protein pore charge and selectivity. Interestingly, E protein IC activity boosted the activation of the NLRP3 inflammasome, leading to IL-1β overproduction. Calcium transport through the E protein IC was the main trigger of this process. These findings strikingly link SARS-CoV E protein IC induced ionic disturbances at the cell level to immunopathological consequences and disease worsening in the infected organism.",,"['Nieto-Torres, Jose L.', 'Verdiá-Báguena, Carmina', 'Jimenez-Guardeño, Jose M.', 'Regla-Nava, Jose A.', 'Castaño-Rodriguez, Carlos', 'Fernandez-Delgado, Raul', 'Torres, Jaume', 'Aguilella, Vicente M.', 'Enjuanes, Luis']",,,,
,PMC,Role of Marine Natural Products in the Genesis of Antiviral Agents,http://dx.doi.org/10.1021/cr4006318,PMC4883660,,,[Image: see text],,"['Gogineni, Vedanjali', 'Schinazi, Raymond F.', 'Hamann, Mark T.']",,,,
,PMC,Mismatching between circulating strains and vaccine strains of influenza: Effect on Hajj pilgrims from both hemispheres,http://dx.doi.org/10.1080/21645515.2015.1085144,PMC4964745,,,"The trivalent seasonal influenza vaccine is expected to provide optimum protection if the vaccine strains match the circulating strains. The effect of worldwide mismatch between the vaccine strains and extant strains on travelers attending Hajj pilgrimage is not known. Annually 2-3 million Muslims coming from north and south hemispheres congregate at Hajj in Mecca, Saudi Arabia, where intense congestion amplifies the risk of respiratory infection up to eight fold. In order to estimate, to what extent mismatching increases the risk of vaccine failure in Hajj pilgrims, we have examined the global data on influenza epidemiology since 2003, in light of the available data from Hajj. These data demonstrate that globally mismatching between circulating and vaccine strains has occurred frequently over the last 12 years, and the mismatch seems to have affected the Hajj pilgrims, however, influenza virus characteristics were studied only in a limited number of Hajj seasons. When the vaccines are different, dual vaccination of travelers by vaccines for southern and northern hemispheres should be considered for Hajj pilgrims whenever logistically feasible. Consideration should also be given to the use of vaccines with broader coverage, i.e., quadrivalent, or higher immunogenicity. Continuous surveillance of influenza at Hajj is important.",,"['Alfelali, Mohammad', 'Khandaker, Gulam', 'Booy, Robert', 'Rashid, Harunor']",,,,
,PMC,The Ethics of Biosafety Considerations in Gain-of-Function Research Resulting in the Creation of Potential Pandemic Pathogens,http://dx.doi.org/10.1136/medethics-2014-102619,PMC4623968,,,"This paper proposes an ethical framework for evaluating biosafety risks of gain-of-function (GOF) experiments that create novel strains of influenza expected to be virulent and transmissible in humans, so-called potential pandemic pathogens (PPP). Such research raises ethical concerns because of the risk that accidental release from a laboratory could lead to extensive or even global spread of a virulent pathogen. Biomedical research ethics has focused largely on human subjects research, while biosafety concerns about accidental infections, seen largely as a problem of occupational health, have been ignored. GOF/PPP research is an example of a small but important class of research where biosafety risks threaten public health, well beyond the small number of persons conducting the research. We argue that bioethical principles that ordinarily apply only to human subjects research should also apply to research that threatens public health, even if, as in GOF/PPP studies, the research involves no human subjects. Specifically we highlight the Nuremberg Code’s requirements of “fruitful results for the good of society, unprocurable by other methods,” and proportionality of risk and humanitarian benefit, as broad ethical principles that recur in later documents on research ethics and should also apply to certain types of research not involving human subjects. We address several potential objections to this view, and conclude with recommendations for bringing these ethical considerations into policy development.",,"['Evans, Nicholas Grieg', 'Lipsitch, Marc', 'Levinson, Meira']",,,,
,PMC,Reply to Dimitrov et al.: VelociSuite technologies are a foundation for rapid therapeutic antibody development,http://dx.doi.org/10.1073/pnas.1513935112,PMC4577199,,,,,"['Kyratsous, Christos A.', 'Olson, William', 'Stahl, Neil']",,,,
,PMC,No evidence for a superior platform to develop therapeutic antibodies rapidly in response to MERS-CoV and other emerging viruses,http://dx.doi.org/10.1073/pnas.1513441112,PMC4577136,,,,,"['Dimitrov, Dimiter S.', 'Jiang, Shibo', 'Ying, Tianlei', 'Tseng, Chien-Te K.', 'Zhang, Linqi', 'Yuen, Kwok-yung']",,,,
,PMC,Transcriptome Sequencing and Development of an Expression Microarray Platform for Liver Infection in Adenovirus Type 5-Infected Syrian Golden Hamsters,http://dx.doi.org/10.1016/j.virol.2015.07.024,PMC4619110,,,"The Syrian golden hamster is an attractive animal for research on infectious diseases and other diseases. We report here the sequencing, assembly, and annotation of the Syrian hamster transcriptome. We include transcripts from ten pooled tissues from a naïve hamster and one stimulated with lipopolysaccharide. Our data set identified 42,707 non-redundant transcripts, representing 34,191 unique genes. Based on the transcriptome data, we generated a custom microarray and used this new platform to investigate the transcriptional response in the Syrian hamster liver following intravenous adenovirus type 5 (Ad5) infection. We found that Ad5 infection caused a massive change in regulation of liver transcripts, with robust up-regulation of genes involved in the antiviral response, indicating that the innate immune response functions in the host defense against Ad5 infection of the liver. The data and novel platforms developed in this study will facilitate further development of this important animal model.",,"['Ying, Baoling', 'Toth, Karoly', 'Spencer, Jacqueline F.', 'Aurora, Rajeev', 'Wold, William S.M.']",,,,
,PMC,"Mucosal, Cellular, and Humoral Immune Responses Induced by Different Live Infectious Bronchitis Virus Vaccination Regimes and Protection Conferred against Infectious Bronchitis Virus Q1 Strain",http://dx.doi.org/10.1128/CVI.00368-15,PMC4550669,,,"The objectives of the present study were to assess the mucosal, cellular, and humoral immune responses induced by two different infectious bronchitis virus (IBV) vaccination regimes and their efficacy against challenge by a variant IBV Q1. One-day-old broiler chicks were vaccinated with live H120 alone (group I) or in combination with CR88 (group II). The two groups were again vaccinated with CR88 at 14 days of age (doa). One group was kept as the control (group III). A significant increase in lachrymal IgA levels was observed at 4 doa and then peaked at 14 doa in the vaccinated groups. The IgA levels in group II were significantly higher than those in group I from 14 doa. Using immunohistochemistry to examine changes in the number of CD4(+) and CD8(+) cells in the trachea, it was found that overall patterns of CD8(+) cells were dominant compared to those of CD4(+) cells in the two vaccinated groups. CD8(+) cells were significantly higher in group II than those in group I at 21 and 28 doa. All groups were challenged oculonasally with a virulent Q1 strain at 28 doa, and their protection was assessed. The two vaccinated groups gave excellent ciliary protection against Q1, although group II's histopathology lesion scores and viral RNA loads in the trachea and kidney showed greater levels of protection than those in group I. These results suggest that greater protection is achieved from the combined vaccination of H120 and CR88 of 1-day-old chicks, followed by CR88 at 14 doa.",,"['Chhabra, Rajesh', 'Forrester, Anne', 'Lemiere, Stephane', 'Awad, Faez', 'Chantrey, Julian', 'Ganapathy, Kannan']",,,,
,PMC,In Vitro Evidence Supports Membrane Alanyl Aminopeptidase N as a Receptor for a Plant Virus in the Pea Aphid Vector,http://dx.doi.org/10.1128/JVI.01479-15,PMC4645670,,,"Insect-borne plant viruses cause significant agricultural losses and jeopardize sustainable global food production. Although blocking plant virus transmission would allow for crop protection, virus receptors in insect vectors are unknown. Here we identify membrane alanyl aminopeptidase N (APN) as a receptor for pea enation mosaic virus (PEMV) coat protein (CP) in the gut of the pea aphid, Acyrthosiphon pisum, using a far-Western blot method. Pulldown and immunofluorescence binding assays and surface plasmon resonance were used to confirm and characterize CP-APN interaction. PEMV virions and a peptide comprised of PEMV CP fused to a proline-rich hinge (-P-) and green fluorescent protein (CP-P-GFP) specifically bound to APN. Recombinant APN expressed in Sf9 cells resulted in internalization of CP-P-GFP, which was visualized by confocal microscopy; such internalization is an expected hallmark of a functional gut receptor. Finally, in assays with aphid gut-derived brush border membrane vesicles, binding of CP-P-GFP competed with binding of GBP3.1, a peptide previously demonstrated to bind to APN in the aphid gut and to impede PEMV uptake into the hemocoel; this finding supports the hypothesis that GBP3.1 and PEMV bind to and compete for the same APN receptor. These in vitro data combined with previously published in vivo experiments (S. Liu, S. Sivakumar, W. O. Sparks, W. A. Miller, and B. C. Bonning, Virology 401:107–116, 2010, http://dx.doi.org/10.1016/j.virol.2010.02.009) support the identification of APN as the first receptor in a plant virus vector. Knowledge of this receptor will provide for technologies based on PEMV-APN interaction designed to block plant virus transmission and to suppress aphid populations. IMPORTANCE A significant proportion of global food production is lost to insect pests. Aphids, in addition to weakening plants by feeding on their sap, are responsible for transmitting about half of the plant viruses vectored by insects. Growers rely heavily on the application of chemical insecticides to manage both aphids and aphid-vectored plant viral disease. To increase our understanding of plant virus-aphid vector interaction, we provide in vitro evidence supporting earlier in vivo work for identification of a receptor protein in the aphid gut called aminopeptidase N, which is responsible for entry of the plant virus pea enation mosaic virus into the pea aphid vector. Enrichment of proteins found on the surface of the aphid gut epithelium resulted in identification of this first aphid gut receptor for a plant virus. This discovery is particularly important since the disruption of plant virus binding to such a receptor may enable the development of a nonchemical strategy for controlling aphid-vectored plant viruses to maximize food production.",,"['Linz, Lucas B.', 'Liu, Sijun', 'Chougule, Nanasaheb P.', 'Bonning, Bryony C.']",,,,
,PMC,"Mechanism of Binding to Ebola Virus Glycoprotein by the ZMapp, ZMAb, and MB-003 Cocktail Antibodies",http://dx.doi.org/10.1128/JVI.01490-15,PMC4621129,,,"Cocktails of monoclonal antibodies (MAbs) that target the surface glycoprotein (GP) of Ebola virus (EBOV) are effective in nonhuman primate models and have been used under emergency compassionate-treatment protocols in human patients. However, the amino acids that form the detailed binding epitopes for the MAbs in the ZMapp, ZMAb, and the related MB-003 cocktails have yet to be identified. Other binding properties that define how each MAb functionally interacts with GP—such as affinity, epitope conservation, and epitope accessibility—also remain largely unknown. To help define how each MAb interacts with GP, here we used comprehensive alanine-scanning mutagenesis (shotgun mutagenesis), neutralization escape, and whole virion binding to define each MAb's specific epitope, epitope accessibility, epitope conservation, and apparent affinity. Each of the six therapeutic MAbs binds nonidentical epitopes in the GP base, glycan cap, or mucin-like domain. Their apparent affinity, epitope complementarity, and epitope accessibility helps explain why MAbs 4G7 and 13C6 are more protective than 2G4 and 1H3. The mucin-like domain MAbs 6D8 and 13F6 bind with the strongest apparent affinity, helping to explain their effectiveness in vivo despite their inability to neutralize virus. IMPORTANCE Ebola virus disease (EVD) can be caused by four different filovirus family members, including Ebola virus (EBOV), which infected 10 times more people in western Africa over the last year than all previous EVD outbreaks combined, with a number of cases distributed across the globe by travelers. Cocktails of inhibitory monoclonal antibodies (MAbs), such as ZMAb, MB-003, and in particular ZMapp, have demonstrated in animal models some of the most significant therapeutic potential for treating EVD, and in 2014, 15 patients were treated with ZMapp or ZMAb under compassionate-use protocols. Here, we have defined the epitope features for the most important therapeutic MAbs against EBOV developed to date. Defining the epitopes and binding characteristics for these MAbs, as well as the commonly used reference MAb KZ52, helps explain their breadth of reactivity against different ebolavirus species, predict viral evasion against these MAbs, and design new cocktails of MAbs with improved complementarity.",,"['Davidson, Edgar', 'Bryan, Christopher', 'Fong, Rachel H.', 'Barnes, Trevor', 'Pfaff, Jennifer M.', 'Mabila, Manu', 'Rucker, Joseph B.', 'Doranz, Benjamin J.']",,,,
,PMC,Middle East Respiratory Syndrome Coronavirus nsp1 Inhibits Host Gene Expression by Selectively Targeting mRNAs Transcribed in the Nucleus while Sparing mRNAs of Cytoplasmic Origin,http://dx.doi.org/10.1128/JVI.01352-15,PMC4621111,,,"The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome CoV (SARS-CoV) represent highly pathogenic human CoVs that share a property to inhibit host gene expression at the posttranscriptional level. Similar to the nonstructural protein 1 (nsp1) of SARS-CoV that inhibits host gene expression at the translational level, we report that MERS-CoV nsp1 also exhibits a conserved function to negatively regulate host gene expression by inhibiting host mRNA translation and inducing the degradation of host mRNAs. Furthermore, like SARS-CoV nsp1, the mRNA degradation activity of MERS-CoV nsp1, most probably triggered by its ability to induce an endonucleolytic RNA cleavage, was separable from its translation inhibitory function. Despite these functional similarities, MERS-CoV nsp1 used a strikingly different strategy that selectively targeted translationally competent host mRNAs for inhibition. While SARS-CoV nsp1 is localized exclusively in the cytoplasm and binds to the 40S ribosomal subunit to gain access to translating mRNAs, MERS-CoV nsp1 was distributed in both the nucleus and the cytoplasm and did not bind stably to the 40S subunit, suggesting a distinctly different mode of targeting translating mRNAs. Interestingly, consistent with this notion, MERS-CoV nsp1 selectively targeted mRNAs, which are transcribed in the nucleus and transported to the cytoplasm, for translation inhibition and mRNA degradation but spared exogenous mRNAs introduced directly into the cytoplasm or virus-like mRNAs that originate in the cytoplasm. Collectively, these data point toward a novel viral strategy wherein the cytoplasmic origin of MERS-CoV mRNAs facilitates their escape from the inhibitory effects of MERS-CoV nsp1. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human CoV that emerged in Saudi Arabia in 2012. MERS-CoV has a zoonotic origin and poses a major threat to public health. However, little is known about the viral factors contributing to the high virulence of MERS-CoV. Many animal viruses, including CoVs, encode proteins that interfere with host gene expression, including those involved in antiviral immune responses, and these viral proteins are often major virulence factors. The nonstructural protein 1 (nsp1) of CoVs is one such protein that inhibits host gene expression and is a major virulence factor. This study presents evidence for a strategy used by MERS-CoV nsp1 to inhibit host gene expression that has not been described previously for any viral protein. The present study represents a meaningful step toward a better understanding of the factors and molecular mechanisms governing the virulence and pathogenesis of MERS-CoV.",,"['Lokugamage, Kumari G.', 'Narayanan, Krishna', 'Nakagawa, Keisuke', 'Terasaki, Kaori', 'Ramirez, Sydney I.', 'Tseng, Chien-Te K.', 'Makino, Shinji']",,,,
,PMC,Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes,http://dx.doi.org/10.1128/JVI.01360-15,PMC4621105,,,"Coronaviruses are RNA viruses with a large zoonotic reservoir and propensity for host switching, representing a real threat for public health, as evidenced by severe acute respiratory syndrome (SARS) and the emerging Middle East respiratory syndrome (MERS). Cellular factors required for their replication are poorly understood. Using genome-wide small interfering RNA (siRNA) screening, we identified 83 novel genes supporting infectious bronchitis virus (IBV) replication in human cells. Thirty of these hits can be placed in a network of interactions with viral proteins and are involved in RNA splicing, membrane trafficking, and ubiquitin conjugation. In addition, our screen reveals an unexpected role for valosin-containing protein (VCP/p97) in early steps of infection. Loss of VCP inhibits a previously uncharacterized degradation of the nucleocapsid N protein. This inhibition derives from virus accumulation in early endosomes, suggesting a role for VCP in the maturation of virus-loaded endosomes. The several host factors identified in this study may provide avenues for targeted therapeutics. IMPORTANCE Coronaviruses are RNA viruses representing a real threat for public health, as evidenced by SARS and the emerging MERS. However, cellular factors required for their replication are poorly understood. Using genome-wide siRNA screening, we identified novel genes supporting infectious bronchitis virus (IBV) replication in human cells. The several host factors identified in this study may provide directions for future research on targeted therapeutics.",,"['Wong, Hui Hui', 'Kumar, Pankaj', 'Tay, Felicia Pei Ling', 'Moreau, Dimitri', 'Liu, Ding Xiang', 'Bard, Frédéric']",,,,
,PMC,Pathogen-Associated Molecular Pattern Recognition of Hepatitis C Virus Transmitted/Founder Variants by RIG-I Is Dependent on U-Core Length,http://dx.doi.org/10.1128/JVI.01964-15,PMC4621103,,,"Despite the introduction of direct-acting antiviral (DAA) drugs against hepatitis C virus (HCV), infection remains a major public health concern because DAA therapeutics do not prevent reinfection and patients can still progress to chronic liver disease. Chronic HCV infection is supported by a variety of viral immune evasion strategies, but, remarkably, 20% to 30% of acute infections spontaneously clear prior to development of adaptive immune responses, thus implicating innate immunity in resolving acute HCV infection. However, the virus-host interactions regulating acute infection are unknown. Transmission of HCV involves one or a few transmitted/founder (T/F) variants. In infected hepatocytes, the retinoic acid-inducible gene I (RIG-I) protein recognizes 5′ triphosphate (5′ppp) of the HCV RNA and a pathogen-associated molecular pattern (PAMP) motif located within the 3′ untranslated region consisting of poly-U/UC. PAMP binding activates RIG-I to induce innate immune signaling and type 1 interferon antiviral defenses. HCV poly-U/UC sequences can differ in length and complexity, suggesting that PAMP diversity in T/F genomes could regulate innate immune control of acute HCV infection. Using 14 unique poly-U/UC sequences from HCV T/F genomes recovered from acute-infection patients, we tested whether RIG-I recognition and innate immune activation correlate with PAMP sequence characteristics. We show that T/F variants are recognized by RIG-I in a manner dependent on length of the U-core motif of the poly-U/UC PAMP and are recognized by RIG-I to induce innate immune responses that restrict acute infection. PAMP recognition of T/F HCV variants by RIG-I may therefore impart innate immune signaling and HCV restriction to impact acute-phase-to-chronic-phase transition. IMPORTANCE Recognition of nonself molecular patterns such as those seen with viral nucleic acids is an essential step in triggering the immune response to virus infection. Innate immunity is induced by hepatitis C virus infection through the recognition of viral RNA by the cellular RIG-I protein, where RIG-I recognizes a poly-uridine/cytosine motif in the viral genome. Variation within this motif may provide an immune evasion strategy for transmitted/founder viruses during acute infection. Using 14 unique poly-U/UC sequences from HCV T/F genomes recovered from acutely infected HCV patients, we demonstrate that RIG-I binding and activation of innate immunity depend primarily on the length of the uridine core within this motif. T/F variants found in acute infection contained longer U cores within the motif and could activate RIG-I and induce innate immune signaling sufficient to restrict viral infection. Thus, recognition of T/F variants by RIG-I could significantly impact the transition from acute to chronic infection.",,"['Kell, Alison', 'Stoddard, Mark', 'Li, Hui', 'Marcotrigiano, Joe', 'Shaw, George M.', 'Gale, Michael']",,,,
,PMC,Structure of the N-terminal dimerization domain of CEACAM7,http://dx.doi.org/10.1107/S2053230X15013576,PMC4555925,,,"CEACAM7 is a human cellular adhesion protein that is expressed on the surface of colon and rectum epithelial cells and is downregulated in colorectal cancers. It achieves cell adhesion through dimerization of the N-terminal IgV domain. The crystal structure of the N-terminal dimerization domain of CEACAM has been determined at 1.47 Å resolution. The overall fold of CEACAM7 is similar to those of CEACAM1 and CEACAM5; however, there are differences, the most notable of which is an insertion that causes the C′′ strand to buckle, leading to the creation of a hydrogen bond in the dimerization interface. The K (dimerization) for CEACAM7 determined by sedimentation equilibrium is tenfold tighter than that measured for CEACAM5. These findings suggest that the dimerization affinities of CEACAMs are modulated via sequence variation in the dimerization surface.",,"['Bonsor, Daniel A.', 'Beckett, Dorothy', 'Sundberg, Eric J.']",,,,
,PMC,Crystallization and preliminary X-ray crystallographic analysis of a nonstructural protein 15 mutant from Human coronavirus 229E,http://dx.doi.org/10.1107/S2053230X15007359,PMC4555923,,,"Nonstructural protein 15 (nsp15), also called endoribonuclease, is a gene product of open reading frame 1b (ORF 1b) in coronaviruses. It is an important enzyme in the transcription/replication process involved in discontinuous negative-strand RNA synthesis. In this work, mutants of nsp15 from Human coronavirus 229E (HCoV-229E) were made based on structural analysis of the homologous nsp15s in Severe acute respiratory syndrome coronavirus (SARS-CoV) and Mouse hepatitis virus (MHV). The I26A/N52A mutant of nsp15 was overexpressed, purified and crystallized, and this mutant led to a trimeric form rather than hexamers or monomers. Crystals of trimeric nsp15 were obtained by the hanging-drop vapour-diffusion method using polyethylene glycol as a precipitant and diffracted to 2.5 Å resolution. The crystals belonged to space group C222(1), with unit-cell parameters a = 85.9, b = 137.5, c = 423.1 Å, α = β = γ = 90°.",,"['Huo, Tong', 'Liu, Xiang']",,,,
,PMC,"A Learner-led, Discussion-based Elective on Emerging Infectious Disease",http://dx.doi.org/10.5688/ajpe79681,PMC4584373,,,"Objective. To implement a learner-led, discussion-based course aimed at exposing second-year pharmacy learners to the study of emerging infectious diseases from a global health perspective and to assess the role and importance of pharmacists in the management of disease outbreaks. Design. Learners examined literature pertinent to an emerging infectious disease in a 3-credit, discussion-based course and participated in peer discussion led by a designated learner. Instructional materials included journal articles, audio-visual presentations, documentaries, book chapters, movies, newspaper/magazine articles, and other materials. Learning outcomes were measured based on the ability of learners to perform critical thinking and analysis, communicate with their peers, and participate in class discussions. Assessment. The course was offered to 2 consecutive cohorts consisting of 14 and 16 learners, respectively. Overall, every learner in the first cohort achieved a final grade of A for the course. In the second cohort, the overall grade distribution consisted of grades of A, B, and C for the course. Learner evaluations indicated that the active-learning, discussion-based environment significantly enhanced interest in the topic and overall performance in the course. Conclusion. The elective course on emerging infectious diseases provided in-depth exposure to disease topics normally not encountered in the pharmacy curriculum. Learners found the material and format valuable, and the course enhanced their appreciation of infectious diseases, research methodology, critical thinking and analysis, and their roles as pharmacists.",,"Mathias, Clinton",,,,
,PMC,"Fyn Activation of mTORC1 Stimulates the IRE1α-JNK Pathway, Leading to Cell Death",http://dx.doi.org/10.1074/jbc.M115.687020,PMC4598989,,,"We previously reported that the skeletal muscle-specific overexpression of Fyn in mice resulted in a severe muscle wasting phenotype despite the activation of mTORC1 signaling. To investigate the bases for the loss of muscle fiber mass, we examined the relationship between Fyn activation of mTORC1, JNK, and endoplasmic reticulum stress. Overexpression of Fyn in skeletal muscle in vivo and in HEK293T cells in culture resulted in the activation of IRE1α and JNK, leading to increased cell death. Fyn synergized with the general endoplasmic reticulum stress inducer thapsigargin, resulting in the activation of IRE1α and further accelerated cell death. Moreover, inhibition of mTORC1 with rapamycin suppressed IRE1α activation and JNK phosphorylation, resulting in protecting cells against Fyn- and thapsigargin-induced cell death. Moreover, rapamycin treatment in vivo reduced the skeletal muscle IRE1α activation in the Fyn-overexpressing transgenic mice. Together, these data demonstrate the presence of a Fyn-induced endoplasmic reticulum stress that occurred, at least in part, through the activation of mTORC1, as well as subsequent activation of the IRE1α-JNK pathway driving cell death.",,"['Wang, Yichen', 'Yamada, Eijiro', 'Zong, Haihong', 'Pessin, Jeffrey E.']",,,,
,PMC,A potent neutralizing IgM mAb targeting the N218 epitope on E2 protein protects against Chikungunya virus pathogenesis,http://dx.doi.org/10.1080/19420862.2015.1083664,PMC4966480,,,"Chikungunya virus (CHIKV) is a medically important human viral pathogen that causes Chikungunya fever accompanied with debilitating and persistent joint pain. Host-elicited or passively-transferred monoclonal antibodies (mAb) are essential mediators of CHIKV clearance. Therefore, this study aimed to generate and characterize a panel of mAbs for their neutralization efficacy against CHIKV infection in a cell-based and murine model. To evaluate their antigenicity and neutralization profile, indirect enzyme-linked immunosorbent assay (ELISA), an immunofluorescence assay (IFA) and a plaque reduction neutralization test were performed on mAbs of IgM isotype. CHIKV escape mutants against mAb 3E7b neutralization were generated, and reverse genetics techniques were then used to create an infectious CHIKV clone with a single mutation. 3E7b was also administered to neonate mice prior or after CHIKV infection. The survival rate, CHIKV burden in tissues and histopathology of the limb muscles were evaluated. Both IgM 3E7b and 8A2c bind strongly to native CHIKV surface and potently neutralize CHIKV replication. Further analyses of 3E7b binding and neutralization of CHIKV single-mutant clones revealed that N218 of CHIKV E2 protein is a potent neutralizing epitope. In a pre-binding neutralization assay, 3E7b blocks CHIKV attachment to permissive cells, possibly by binding to the surface-accessible E2-N218 residue. Prophylactic administration of 3E7b to neonate mice markedly reduced viremia and protected against CHIKV pathogenesis in various mice tissues. Given therapeutically at 4 h post-infection, 3E7b conferred 100% survival rate and similarly reduced CHIKV load in most mice tissues except the limb muscles. Collectively, these findings highlight the usefulness of 3E7b for future prophylactic or epitope-based vaccine design.",,"['Lam, Shirley', 'Nyo, Min', 'Phuektes, Patchara', 'Yew, Chow Wenn', 'Tan, Yee Joo', 'Chu, Justin Jang Hann']",,,,
,PMC,Animal extremists' threats to neurologic research continue: Neuroreality II,http://dx.doi.org/10.1212/WNL.0000000000001764,PMC4553027,,,,,"['Beversdorf, David Q.', 'Roos, Raymond P.', 'Hauser, W. Allen', 'Lennon, Vanda A.', 'Mehler, Mark F.']",,,,
,PMC,A research agenda for aging in China in the 21st century,http://dx.doi.org/10.1016/j.arr.2015.08.003,PMC5179143,,,"China is encountering formidable healthcare challenges brought about by the problem of aging. By 2050, there will be 400 million Chinese citizens aged 65+, 150 million of whom will be 80+. The undesirable consequences of the one-child policy, rural-to-urban migration, and expansion of the population of ‘empty nest ’ elders are eroding the traditional family care of the elders, further exacerbating the burden borne by the current public healthcare system. The challenges of geriatric care demand prompt attention by proposing strategies for improvement in several key areas. Major diseases of the elderly that need more attention include chronic non-communicable diseases and mental health disorders. We suggest the establishment of a home care-dominated geriatric care system, and a proactive role for researchers on aging in reforming geriatric care through policy dialogs. We propose ideas for preparation of the impending aging burden and the creation of a nurturing environment conducive to healthy aging in China.",,"['Fang, Evandro Fei', 'Scheibye-Knudsen, Morten', 'Jahn, Heiko J.', 'Li, Juan', 'Ling, Li', 'Guo, Hongwei', 'Zhu, Xinqiang', 'Preedy, Victor', 'Lu, Huiming', 'Bohr, Vilhelm A.', 'Chan, Wai Yee', 'Liu, Yuanli', 'Ng, Tzi Bun']",,,,
,PMC,Diminazene enhances stability of atherosclerotic plaques in ApoE-deficient mice,http://dx.doi.org/10.1016/j.vph.2015.08.014,PMC5589185,,,"Angiotensin (Ang) II contributes to the development of atherosclerosis, while Ang-(1–7) has atheroprotective actions. Accordingly, angiotensin-converting enzyme 2 (ACE2), which breaks-down Ang II and forms Ang-(1–7), has been suggested as a target against atherosclerosis. Here we investigated the actions of diminazene, a recently developed ACE2 activator compound, in a model of vulnerable atherosclerotic plaque. Atherosclerotic plaque formation was induced in the carotid artery of ApoE-deficient mice by a shear stress (SS) modiffer device. The animals were treated with diminazene (15 mg/kg/day) or vehicle. ACE2 was strongly expressed in the aortic root and low SS-induced carotid plaques, but poorly expressed in the oscillatory SS-induced carotid plaques. Diminazene treatment did not change the lesion size, but ameliorated the composition of aortic root and low SS-induced carotid plaques by increasing collagen content and decreasing both MMP-9 expression and macrophage infiltration. Interestingly, these beneficial effects were not observed in the oscillatory SS-induced plaque. Additionally, diminazene treatment decreased intraplaque ICAM-1 and VCAM-1 expression, circulating cytokine and chemokine levels and serum triglycerides. In summary, ACE2 was distinctively expressed in atherosclerotic plaques, which depends on the local pattern of shear stress. Moreover, diminazene treatment enhances the stability of atherosclerotic plaques.",,"['Fraga-Silva, Rodrigo A.', 'Montecucco, Fabrizio', 'Costa-Fraga, Fabiana P.', 'Nencioni, Alessio', 'Caffa, Irene', 'Bragina, Maiia E.', 'Mach, François', 'Raizada, Mohan K.', 'Santos, Robson A.S.', 'da Silva, Rafaela F.', 'Stergiopulos, Nikolaos']",,,,
,PMC,Detecting respiratory viral RNA using expanded genetic alphabets and self-avoiding DNA,http://dx.doi.org/10.1016/j.ab.2015.08.015,PMC4733849,,,"Nucleic acid (NA)-targeted tests detect and quantify viral DNA and RNA (collectively xNA) to support epidemiological surveillance and, in individual patients, to guide therapy. They commonly use polymerase chain reaction (PCR) and reverse transcription PCR. Although these all have rapid turnaround, they are expensive to run. Multiplexing would allow their cost to be spread over multiple targets, but often only with lower sensitivity and accuracy, noise, false positives, and false negatives; these arise by interactions between the multiple nucleic acid primers and probes in a multiplexed kit. Here we offer a multiplexed assay for a panel of respiratory viruses that mitigates these problems by combining several nucleic acid analogs from the emerging field of synthetic biology: (i) self-avoiding molecular recognition systems (SAMRSs), which facilitate multiplexing, and (ii) artificially expanded genetic information systems (AEGISs), which enable low-noise PCR. These are supplemented by “transliteration” technology, which converts standard nucleotides in a target to AEGIS nucleotides in a product, improving hybridization. The combination supports a multiplexed Luminex-based respiratory panel that potentially differentiates influenza viruses A and B, respiratory syncytial virus, severe acute respiratory syndrome coronavirus (SARS), and Middle East respiratory syndrome (MERS) coronavirus, detecting as few as 10 MERS virions in a 20-μl sample.",,"['Glushakova, Lyudmyla G.', 'Sharma, Nidhi', 'Hoshika, Shuichi', 'Bradley, Andrea C.', 'Bradley, Kevin M.', 'Yang, Zunyi', 'Benner, Steven A.']",,,,
,PMC,Towards Detection and Diagnosis of Ebola Virus Disease at Point-of-Care,http://dx.doi.org/10.1016/j.bios.2015.08.040,PMC4601610,,,"Ebola outbreak-2014 (mainly Zaire strain related Ebola virus) has been declared most widely spread deadly persistent epidemic due to unavailability of rapid diagnostic, detection, and therapeutics. Ebola virus disease (EVD), a severe viral hemorrhagic fever syndrome caused by Ebola virus (EBOV) is transmitted by direct contact with the body fluids of infected person and objects contaminated with virus or infected animals. World Health Organization (WHO) has declared EVD epidemic as public health emergency of international concern with severe global economic burden. At fatal EBOV infection stage, patients usually die before the antibody response. Currently, rapid blood tests to diagnose EBOV infection include the antigen or antibodies capture using ELISA and RNA detection using RT/Q-PCR within 3–10 days after the onset of symptoms. Moreover, few nanotechnology-based colorimetric and paper-based immunoassay methods have been recently reported to detect Ebola virus. Unfortunately, these methods are limited to laboratory only. As state-of-the art (SoA) diagnostics time to confirm Ebola infection, varies from 6 hours to about 3 days, it causes delay in therapeutic approaches. Thus developing a cost-effective, rapid, sensitive, and selective sensor to detect EVD at point-of-care (POC) is certainly worth exploring to establish rapid diagnostics to decide therapeutics. This review highlights SoA of Ebola diagnostics and also a call to develop rapid, selective and sensitive POC detection of EBOV for global health care. We propose that adopting miniaturized electrochemical EBOV immunosensing can detect virus level at pM concentration within ~40 minute compared to 3 days of ELISA test at nM levels.",,"['Kaushik, Ajeet', 'Tiwari, Sneham', 'Jayant, Rahul Dev', 'Marty, Aileen', 'Nair, Madhavan']",,,,
,PMC,Ebola Risk and Preparedness: A National Survey of Internists,http://dx.doi.org/10.1007/s11606-015-3493-1,PMC4762833,,,"BACKGROUND: The 2014–2015 Ebola virus disease (Ebola) epidemic centered in West Africa highlighted recurring challenges in the United States regarding risk communication and preparedness during global epidemics. OBJECTIVE: To investigate perceptions, preparedness, and knowledge among U.S. internists with regard to Ebola risk. DESIGN: Cross-sectional Web-based national survey distributed by e-mail between December 2014 and January 2015. PARTICIPANTS: Practicing U.S. internists participating in a research panel representative of American College of Physicians (ACP) membership. MAIN MEASURES: Respondents’ perceptions of Ebola, reported sources of information, and reported management of possible Ebola cases. The primary predictor was the possibility of encountering Ebola (based on respondents’ geographic proximity to designated airports or confirmed Ebola cases, or on their patients’ travel histories). Pre-specified outcomes included reported management intensity in clinical vignettes involving patients at low risk of symptomatic Ebola as well as reported Ebola preparedness. KEY RESULTS: The survey response rate was 46.1 %. Among the 202 respondents, 9.9 % (95 % CI 6.2–14.9 %) reported that they had recently evaluated a patient who had traveled to West Africa. Seventy percent (95 % CI 63.0–76.0 %) reported a practice-level protocol. The Centers for Disease Control and Prevention (CDC) was the most popular source for Ebola information (75.2 %, 95 % CI 68.7–81.0 %). Most respondents felt very (45.0 %) or somewhat prepared (52.0 %) to communicate information about or diagnose Ebola, especially those with the possibility of encountering Ebola and those who reported medical journals, professional groups, or government as information sources. One-fifth of respondents (19.8 %, 95 % CI 14.5–26.0 %) reported overly intensive management for low-risk patients. Those with the possibility of encountering Ebola were less likely to report overly intensive management (3.1 vs. 22.9 %, p = 0.011). CONCLUSIONS: Internists had wide-ranging views and understanding of Ebola risk; those least likely to encounter Ebola were most likely to be overly aggressive in managing patients at low risk. Our findings underscore the need for better risk communication through various information channels to empower frontline providers in infectious disease outbreaks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11606-015-3493-1) contains supplementary material, which is available to authorized users.",,"['Ganguli, Ishani', 'Chang, Yuchiao', 'Weissman, Arlene', 'Armstrong, Katrina', 'Metlay, Joshua P.']",,,,
,PMC,Host Avian Beta-Defensin and Toll-Like Receptor Responses of Pigeons following Infection with Pigeon Paramyxovirus Type 1,http://dx.doi.org/10.1128/AEM.01413-15,PMC4542233,,,"The high morbidity and mortality in pigeons caused by pigeon paramyxovirus type 1 (PPMV-1) highlights the need for new insights into the host immune response and novel treatment approaches. Host defense peptides (HDPs) are key components of the innate immune system. In this study, three novel avian β-defensins (AvBDs 2, 7, and 10) were characterized in pigeons and shown to possess direct antiviral activity against PPMV-1 in vitro. In addition, we evaluated the mRNA expression of these AvBDs and other immune-related genes in tissues of 2-month-old infected pigeons at 3 and 7 days postinfection. We observed that the expression of AvBD2 in the cecal tonsil, lungs, and proventriculus, as well as the expression of AvBD10 in the spleen, lungs, proventriculus, and kidneys, was upregulated in infected pigeons. Similarly, the expression of both Toll-like receptor 3 (TLR3) and TLR7 was increased in the spleen, trachea, and proventriculus, while TLR15 expression was increased only in the lungs of infected pigeons. In addition, inducible nitric oxide synthase (iNOS) expression was upregulated in the spleen, the bursa of Fabricius, the trachea, and the proventriculus of infected pigeons. Furthermore, we observed a high correlation between the expression of AvBD2 and the expression of either TLR7 or TLR15, as well as between AvBD10 expression and either TLR3 or TLR7 expression in respective tissues. The results suggest that PPMV-1 infection can induce innate host responses characterized by the activation of TLRs, particularly TLR3 and TLR7, AvBDs (2 and 10), and iNOS in pigeons.",,"['Li, Yanyan', 'Xu, Qianqian', 'Zhang, Tingting', 'Gao, Mengying', 'Wang, Qiuling', 'Han, Zongxi', 'Shao, Yuhao', 'Ma, Deying', 'Liu, Shengwang']",,,,
,PMC,X-ray Structural and Functional Studies of the Three Tandemly Linked Domains of Non-structural Protein 3 (nsp3) from Murine Hepatitis Virus Reveal Conserved Functions,http://dx.doi.org/10.1074/jbc.M115.662130,PMC4646180,,,"Murine hepatitis virus (MHV) has long served as a model system for the study of coronaviruses. Non-structural protein 3 (nsp3) is the largest nsp in the coronavirus genome, and it contains multiple functional domains that are required for coronavirus replication. Despite the numerous functional studies on MHV and its nsp3 domain, the structure of only one domain in nsp3, the small ubiquitin-like domain 1 (Ubl1), has been determined. We report here the x-ray structure of three tandemly linked domains of MHV nsp3, including the papain-like protease 2 (PLP2) catalytic domain, the ubiquitin-like domain 2 (Ubl2), and a third domain that we call the DPUP (domain preceding Ubl2 and PLP2) domain. DPUP has close structural similarity to the severe acute respiratory syndrome coronavirus unique domain C (SUD-C), suggesting that this domain may not be unique to the severe acute respiratory syndrome coronavirus. The PLP2 catalytic domain was found to have both deubiquitinating and deISGylating isopeptidase activities in addition to proteolytic activity. A computationally derived model of MHV PLP2 bound to ubiquitin was generated, and the potential interactions between ubiquitin and PLP2 were probed by site-directed mutagenesis. These studies extend substantially our structural knowledge of MHV nsp3, providing a platform for further investigation of the role of nsp3 domains in MHV viral replication.",,"['Chen, Yafang', 'Savinov, Sergey N.', 'Mielech, Anna M.', 'Cao, Thu', 'Baker, Susan C.', 'Mesecar, Andrew D.']",,,,
,PMC,"Human and Murine IFIT1 Proteins Do Not Restrict Infection of Negative-Sense RNA Viruses of the Orthomyxoviridae, Bunyaviridae, and Filoviridae Families",http://dx.doi.org/10.1128/JVI.00996-15,PMC4542382,,,"Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) is a host protein with reported cell-intrinsic antiviral activity against several RNA viruses. The proposed basis for the activity against negative-sense RNA viruses is the binding to exposed 5′-triphosphates (5′-ppp) on the genome of viral RNA. However, recent studies reported relatively low binding affinities of IFIT1 for 5′-ppp RNA, suggesting that IFIT1 may not interact efficiently with this moiety under physiological conditions. To evaluate the ability of IFIT1 to have an impact on negative-sense RNA viruses, we infected Ifit1(−/−) and wild-type control mice and primary cells with four negative-sense RNA viruses (influenza A virus [IAV], La Crosse virus [LACV], Oropouche virus [OROV], and Ebola virus) corresponding to three distinct families. Unexpectedly, a lack of Ifit1 gene expression did not result in increased infection by any of these viruses in cell culture. Analogously, morbidity, mortality, and viral burdens in tissues were identical between Ifit1(−/−) and control mice after infection with IAV, LACV, or OROV. Finally, deletion of the human IFIT1 protein in A549 cells did not affect IAV replication or infection, and reciprocally, ectopic expression of IFIT1 in HEK293T cells did not inhibit IAV infection. To explain the lack of antiviral activity against IAV, we measured the binding affinity of IFIT1 for RNA oligonucleotides resembling the 5′ ends of IAV gene segments. The affinity for 5′-ppp RNA was approximately 10-fold lower than that for non-2′-O-methylated (cap 0) RNA oligonucleotides. Based on this analysis, we conclude that IFIT1 is not a dominant restriction factor against negative-sense RNA viruses. IMPORTANCE Negative-sense RNA viruses, including influenza virus and Ebola virus, have been responsible for some of the most deadly outbreaks in recent history. The host interferon response and induction of antiviral genes contribute to the control of infections by these viruses. IFIT1 is highly induced after virus infection and reportedly has antiviral activity against several RNA and DNA viruses. However, its role in restricting infection by negative-sense RNA viruses remains unclear. In this study, we evaluated the ability of IFIT1 to inhibit negative-sense RNA virus replication and pathogenesis both in vitro and in vivo. Detailed cell culture and animal studies demonstrated that IFIT1 is not a dominant restriction factor against three different families of negative-sense RNA viruses.",,"['Pinto, Amelia K.', 'Williams, Graham D.', 'Szretter, Kristy J.', 'White, James P.', 'Proença-Módena, José Luiz', 'Liu, Gai', 'Olejnik, Judith', 'Brien, James D.', 'Ebihara, Hideki', 'Mühlberger, Elke', 'Amarasinghe, Gaya', 'Diamond, Michael S.', 'Boon, Adrianus C. M.']",,,,
,PMC,"Double-Stranded RNA Is Detected by Immunofluorescence Analysis in RNA and DNA Virus Infections, Including Those by Negative-Stranded RNA Viruses",http://dx.doi.org/10.1128/JVI.01299-15,PMC4542381,,,"Early biochemical studies of viral replication suggested that most viruses produce double-stranded RNA (dsRNA), which is essential for the induction of the host immune response. However, it was reported in 2006 that dsRNA could be detected by immunofluorescence antibody staining in double-stranded DNA and positive-strand RNA virus infections but not in negative-strand RNA virus infections. Other reports in the literature seemed to support these observations. This suggested that negative-strand RNA viruses produce little, if any, dsRNA or that more efficient viral countermeasures to mask dsRNA are mounted. Because of our interest in the use of dsRNA antibodies for virus discovery, particularly in pathological specimens, we wanted to determine how universal immunostaining for dsRNA might be in animal virus infections. We have detected the in situ formation of dsRNA in cells infected with vesicular stomatitis virus, measles virus, influenza A virus, and Nyamanini virus, which represent viruses from different negative-strand RNA virus families. dsRNA was also detected in cells infected with lymphocytic choriomeningitis virus, an ambisense RNA virus, and minute virus of mice (MVM), a single-stranded DNA (ssDNA) parvovirus, but not hepatitis B virus. Although dsRNA staining was primarily observed in the cytoplasm, it was also seen in the nucleus of cells infected with influenza A virus, Nyamanini virus, and MVM. Thus, it is likely that most animal virus infections produce dsRNA species that can be detected by immunofluorescence staining. The apoptosis induced in several uninfected cell lines failed to upregulate dsRNA formation. IMPORTANCE An effective antiviral host immune response depends on recognition of viral invasion and an intact innate immune system as a first line of defense. Double-stranded RNA (dsRNA) is a viral product essential for the induction of innate immunity, leading to the production of type I interferons (IFNs) and the activation of hundreds of IFN-stimulated genes. The present study demonstrates that infections, including those by ssDNA viruses and positive- and negative-strand RNA viruses, produce dsRNAs detectable by standard immunofluorescence staining. While dsRNA staining was primarily observed in the cytoplasm, nuclear staining was also present in some RNA and DNA virus infections. The nucleus is unlikely to have pathogen-associated molecular pattern (PAMP) receptors for dsRNA because of the presence of host dsRNA molecules. Thus, it is likely that most animal virus infections produce dsRNA species detectable by immunofluorescence staining, which may prove useful in viral discovery as well.",,"['Son, Kyung-No', 'Liang, Zhiguo', 'Lipton, Howard L.']",,,,
,PMC,Myd88 Initiates Early Innate Immune Responses and Promotes CD4 T Cells during Coronavirus Encephalomyelitis,http://dx.doi.org/10.1128/JVI.01199-15,PMC4542380,,,"Myd88 signaling is critical to the control of numerous central nervous system (CNS) infections by promoting both innate and adaptive immune responses. Nevertheless, the extent to which Myd88 regulates type I interferon (IFN) versus proinflammatory factors and T cell function, as well as the anatomical site of action, varies extensively with the pathogen. CNS infection by neurotropic coronavirus with replication confined to the brain and spinal cord induces protective IFN-α/β via Myd88-independent activation of melanoma differentiation-associated gene 5 (MDA5). However, a contribution of Myd88-dependent signals to CNS pathogenesis has not been assessed. Infected Myd88(−/−) mice failed to control virus, exhibited enhanced clinical disease coincident with increased demyelination, and succumbed to infection within 3 weeks. The induction of IFN-α/β, as well as of proinflammatory cytokines and chemokines, was impaired early during infection. However, defects in both IFN-α/β and select proinflammatory factors were rapidly overcome prior to T cell recruitment. Myd88 deficiency also specifically blunted myeloid and CD4 T cell recruitment into the CNS without affecting CD8 T cells. Moreover, CD4 T cells but not CD8 T cells were impaired in IFN-γ production. Ineffective virus control indeed correlated most prominently with reduced antiviral IFN-γ in the CNS of Myd88(−/−) mice. The results demonstrate a crucial role for Myd88 both in early induction of innate immune responses during coronavirus-induced encephalomyelitis and in specifically promoting protective CD4 T cell activation. In the absence of these responses, functional CD8 T cells are insufficient to control viral spread within the CNS, resulting in severe demyelination. IMPORTANCE During central nervous system (CNS) infections, signaling through the adaptor protein Myd88 promotes both innate and adaptive immune responses. The extent to which Myd88 regulates antiviral type I IFN, proinflammatory factors, adaptive immunity, and pathology is pathogen dependent. These results reveal that Myd88 protects from lethal neurotropic coronavirus-induced encephalomyelitis by accelerating but not enhancing the induction of IFN-α/β, as well as by promoting peripheral activation and CNS accumulation of virus-specific CD4 T cells secreting IFN-γ. By controlling both early innate immune responses and CD4 T cell-mediated antiviral IFN-γ, Myd88 signaling limits the initial viral dissemination and is vital for T cell-mediated control of viral loads. Uncontrolled viral replication in the absence of Myd88 leads to severe demyelination and pathology despite overall reduced inflammatory responses. These data support a vital role of Myd88 signaling in protective antimicrobial functions in the CNS by promoting proinflammatory mediators and T cell-mediated IFN-γ production.",,"['Butchi, Niranjan', 'Kapil, Parul', 'Puntambekar, Shweta', 'Stohlman, Stephen A.', 'Hinton, David R.', 'Bergmann, Cornelia C.']",,,,
,PMC,A Coronavirus E Protein Is Present in Two Distinct Pools with Different Effects on Assembly and the Secretory Pathway,http://dx.doi.org/10.1128/JVI.01237-15,PMC4542375,,,"Coronaviruses (CoVs) assemble by budding into the lumen of the early Golgi complex prior to exocytosis. The small CoV envelope (E) protein plays roles in assembly, virion release, and pathogenesis. CoV E has a single hydrophobic domain (HD), is targeted to Golgi complex membranes, and has cation channel activity in vitro. However, the precise functions of the CoV E protein during infection are still enigmatic. Structural data for the severe acute respiratory syndrome (SARS)-CoV E protein suggest that it assembles into a homopentamer. Specific residues in the HD regulate the ion-conducting pore formed by SARS-CoV E in artificial bilayers and the pathogenicity of the virus during infection. The E protein from the avian infectious bronchitis virus (IBV) has dramatic effects on the secretory system which require residues in the HD. Here, we use the known structural data from SARS-CoV E to infer the residues important for ion channel activity and the oligomerization of IBV E. We present biochemical data for the formation of two distinct oligomeric pools of IBV E in transfected and infected cells and the residues required for their formation. A high-order oligomer of IBV E is required for the production of virus-like particles (VLPs), implicating this form of the protein in virion assembly. Additionally, disruption of the secretory pathway by IBV E correlates with a form that is likely monomeric, suggesting that the effects on the secretory pathway are independent of E ion channel activity. IMPORTANCE CoVs are important human pathogens with significant zoonotic potential, as demonstrated by the emergence of SARS-CoV and Middle East respiratory syndrome (MERS)-CoV. Progress has been made toward identifying potential vaccine candidates in mouse models of CoV infection, including the use of attenuated viruses that lack the CoV E protein or express E-protein mutants. However, no approved vaccines or antiviral therapeutics exist. We previously reported that the hydrophobic domain of the IBV E protein, a putative viroporin, causes disruption of the mammalian secretory pathway when exogenously expressed in cells. Understanding the mechanism of this disruption could lead to the identification of novel antiviral therapeutics. Here, we present biochemical evidence for two distinct oligomeric forms of IBV E, one essential for assembly and the other with a role in disruption of the secretory pathway. Discovery of two forms of CoV E protein will provide additional targets for antiviral therapeutics.",,"['Westerbeck, Jason W.', 'Machamer, Carolyn E.']",,,,
,PMC,The Interferon-Inducible Protein Tetherin Inhibits Hepatitis B Virus Virion Secretion,http://dx.doi.org/10.1128/JVI.00933-15,PMC4542364,,,"Interferon alpha (IFN-α) is an approved medication for chronic hepatitis B therapy. Besides acting as an immunomodulator, IFN-α elicits a pleiotropic antiviral state in hepatitis B virus (HBV)-infected hepatocytes, but whether or not IFN-α impedes the late steps of the HBV life cycle, such as HBV secretion, remains elusive. Here we report that IFN-α treatment of HepAD38 cells with established HBV replication selectively reduced HBV virion release without altering intracellular viral replication or the secretion of HBV subviral particles and nonenveloped capsids. In search of the interferon-stimulated gene(s) that is responsible for the reduction of HBV virion release, we found that tetherin, a broad-spectrum antiviral transmembrane protein that inhibits the egress of a variety of enveloped viruses, was highly induced by IFN-α in HepAD38 cells and in primary human hepatocytes. We further demonstrated that the expression of full-length tetherin, but not the C-terminal glycosylphosphatidylinositol (GPI) anchor-truncated form, inhibited HBV virion egress from HepAD38 cells. In addition, GPI anchor-truncated tetherin exhibited a dominant-negative effect and was incorporated into the liberated virions. We also found colocalization of tetherin and HBV L protein at the intracellular multivesicular body, where the budding of HBV virions takes place. In line with this, electron microscopy demonstrated that HBV virions were tethered in the lumen of the cisterna membrane under tetherin expression. Finally, knockdown of tetherin or overexpression of dominant negative tetherin attenuated the IFN-α-mediated reduction of HBV virion release. Taken together, our study suggests that IFN-α inhibits HBV virion egress from hepatocytes through the induction of tetherin. IMPORTANCE Tetherin is a host restriction factor that blocks the egress of a variety of enveloped viruses through tethering the budding virions on the cell surface with its membrane anchor domains. Here we report that interferon directly and selectively inhibits the secretion of HBV virions, but not subviral particles or nonenveloped capsids, through the induction of tetherin in hepatocyte-derived cells. The antiviral function of tetherin requires the carboxyl-terminal GPI anchor, while the GPI anchor deletion mutant exhibits dominant negative activity and attaches to liberated HBV virions. Consistent with the fact that HBV is an intracellular budding virus, microscopy analyses demonstrated that the tethering of HBV virions occurs in the intracellular cisterna and that tetherin colocalizes with HBV virions on the multivesicular body, which is the HBV virion budding site. Our study not only expands the antiviral spectrum of tetherin but also sheds light on the mechanisms of interferon-elicited anti-HBV responses.",,"['Yan, Ran', 'Zhao, Xuesen', 'Cai, Dawei', 'Liu, Yuanjie', 'Block, Timothy M.', 'Guo, Ju-Tao', 'Guo, Haitao']",,,,
,PMC,Tetherin Sensitivity of Influenza A Viruses Is Strain Specific: Role of Hemagglutinin and Neuraminidase,http://dx.doi.org/10.1128/JVI.00615-15,PMC4542344,,,"The expression of the antiviral host cell factor tetherin is induced by interferon and can inhibit the release of enveloped viruses from infected cells. The Vpu protein of HIV-1 antagonizes the antiviral activity of tetherin, and tetherin antagonists with Vpu-like activity have been identified in other viruses. In contrast, it is incompletely understood whether tetherin inhibits influenza A virus (FLUAV) release and whether FLUAV encodes tetherin antagonists. Here, we show that release of several laboratory-adapted FLUAV strains and a seasonal FLUAV strain is inhibited by tetherin, while pandemic FLUAV A/Hamburg/4/2009 is resistant. Studies with a virus-like particle system and analysis of reassortant viruses provided evidence that the viral hemagglutinin (HA) is an important determinant of tetherin antagonism but requires the presence of its cognate neuraminidase (NA) to inhibit tetherin. Finally, tetherin antagonism by FLUAV was dependent on the virion context, since retrovirus release from tetherin-positive cells was not rescued, and correlated with an HA- and NA-dependent reduction in tetherin expression. In sum, our study identifies HA and NA proteins of certain pandemic FLUAV as tetherin antagonists, which has important implications for understanding FLUAV pathogenesis. IMPORTANCE Influenza A virus (FLUAV) infection is responsible for substantial global morbidity and mortality, and understanding how the virus evades the immune defenses of the host may uncover novel targets for antiviral intervention. Tetherin is an antiviral effector molecule of the innate immune system which can contribute to control of viral invasion. However, it has been unclear whether FLUAV is inhibited by tetherin and whether these viruses encode tetherin-antagonizing proteins. Our observation that several pandemic FLUAV strains can counteract tetherin via their HA and NA proteins identifies these proteins as novel tetherin antagonists and indicates that HA/NA-dependent inactivation of innate defenses may contribute to the efficient spread of pandemic FLUAV.",,"['Gnirß, Kerstin', 'Zmora, Pawel', 'Blazejewska, Paulina', 'Winkler, Michael', 'Lins, Anika', 'Nehlmeier, Inga', 'Gärtner, Sabine', 'Moldenhauer, Anna-Sophie', 'Hofmann-Winkler, Heike', 'Wolff, Thorsten', 'Schindler, Michael', 'Pöhlmann, Stefan']",,,,
,PMC,A synthetic consensus anti–spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates,http://dx.doi.org/10.1126/scitranslmed.aac7462,PMC4573558,,,"First identified in 2012, Middle East respiratory syndrome (MERS) is caused by an emerging human coronavirus, which is distinct from the severe acute respiratory syndrome coronavirus (SARS-CoV), and represents a novel member of the lineage C betacoronoviruses. Since its identification, MERS coronavirus (MERS-CoV) has been linked to more than 1372 infections manifesting with severe morbidity and, often, mortality (about 495 deaths) in the Arabian Peninsula, Europe, and, most recently, the United States. Human-to-human transmission has been documented, with nosocomial transmission appearing to be an important route of infection. The recent increase in cases of MERS in the Middle East coupled with the lack of approved antiviral therapies or vaccines to treat or prevent this infection are causes for concern. We report on the development of a synthetic DNA vaccine against MERS-CoV. An optimized DNA vaccine encoding the MERS spike protein induced potent cellular immunity and antigen-specific neutralizing antibodies in mice, macaques, and camels. Vaccinated rhesus macaques seroconverted rapidly and exhibited high levels of virus-neutralizing activity. Upon MERS viral challenge, all of the monkeys in the control-vaccinated group developed characteristic disease, including pneumonia. Vaccinated macaques were protected and failed to demonstrate any clinical or radiographic signs of pneumonia. These studies demonstrate that a consensus MERS spike protein synthetic DNA vaccine can induce protective responses against viral challenge, indicating that this strategy may have value as a possible vaccine modality against this emerging pathogen.",,"['Muthumani, Karuppiah', 'Falzarano, Darryl', 'Reuschel, Emma L.', 'Tingey, Colleen', 'Flingai, Seleeke', 'Villarreal, Daniel O.', 'Wise, Megan', 'Patel, Ami', 'Izmirly, Abdullah', 'Aljuaid, Abdulelah', 'Seliga, Alecia M.', 'Soule, Geoff', 'Morrow, Matthew', 'Kraynyak, Kimberly A.', 'Khan, Amir S.', 'Scott, Dana P.', 'Feldmann, Friederike', 'LaCasse, Rachel', 'Meade-White, Kimberly', 'Okumura, Atsushi', 'Ugen, Kenneth E.', 'Sardesai, Niranjan Y.', 'Kim, J. Joseph', 'Kobinger, Gary', 'Feldmann, Heinz', 'Weiner, David B.']",,,,
,PMC,Infectious Middle East Respiratory Syndrome Coronavirus Excretion and Serotype Variability Based on Live Virus Isolates from Patients in Saudi Arabia,http://dx.doi.org/10.1128/JCM.01368-15,PMC4540943,,,"The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 1,082 people, including 439 fatalities. So far, no empirical virus isolation study has been done to elucidate infectious virus secretion or serotype variability. Here, we used 51 respiratory samples from 32 patients with confirmed MERS-CoV infection for virus isolation in Vero B4 and Caco-2 cells. We found Caco-2 cells to significantly enhance isolation success over routinely used Vero cells. Isolation success correlated with viral RNA concentration and time after diagnosis as well as with the amount of IgA antibodies secreted in respiratory samples used for isolation. Results from plaque reduction neutralization assays using a representative range of serum samples and virus isolates suggested that all circulating human MERS-CoV strains represent one single serotype. The choice of prototype strain is not likely to influence the success of candidate MERS-CoV vaccines. However, vaccine formulations should be evaluated for their potential to induce IgA.",,"['Muth, Doreen', 'Corman, Victor M.', 'Meyer, Benjamin', 'Assiri, Abdullah', 'Al-Masri, Malak', 'Farah, Mohamed', 'Steinhagen, Katja', 'Lattwein, Erik', 'Al-Tawfiq, Jaffar A.', 'Albarrak, Ali', 'Müller, Marcel A.', 'Drosten, Christian', 'Memish, Ziad A.']",,,,
,PMC,Upstream Disaster Management to Support People Experiencing Homelessness,http://dx.doi.org/10.1371/currents.dis.95f6b76789ce910bae08b6dc1f252c7d,PMC4552382,26346842,CC BY,"The unique context of day-to-day living for people who are chronically homeless or living with housing insecurity puts them at high risk during community disasters. The impacts of extreme events, such as flooding, storms, riots, and other sources of community disruption, underscore the importance of preparedness efforts and fostering community resilience. This study is part of larger initiative focused on enhancing resilience and preparedness among high risk populations. The purpose of this study was to explore critical issues and strategies to promote resilience and disaster preparedness among people who are homeless in Canada. A sample of interviews (n=21) from key informants across Canada was analyzed to explore existing programs and supports for homeless populations. The data was selected from a larger sample of (n=43) interviews focused on programs and supports for people who are at heightened risk for negative impacts during disasters. Qualitative content analysis was used to extract emergent themes and develop a model of multi-level collaboration to support disaster resilience among people who are homeless. The results indicate there is a need for more upstream continuity planning, collaboration and communication between the emergency management sector and community service organizations that support people who are homeless. Prioritization and investment in the social determinants of health and community supports is necessary to promote resilience among this high-risk population. The findings from this study highlight the importance of acknowledging community support organizations as assets in disaster preparedness. Day-to-day resilience is an ongoing theme for people who are chronically homeless or living with housing insecurity. Upstream investment to build adaptive capacity and collaborate with community organizations is an important strategy to enhance community resilience.",2015 Aug 18,"['Sundareswaran, Madura', 'Ghazzawi, Andrea', ""O'Sullivan, Tracey L.""]",PLoS Curr,,,
,PMC,In This Issue,http://dx.doi.org/10.1073/iti3315112,PMC4547269,,,,,,,,,
,PMC,In Vivo Effects of Mesenchymal Stromal Cells in Two Patients With Severe Acute Respiratory Distress Syndrome,http://dx.doi.org/10.5966/sctm.2015-0021,PMC4572899,,,"Mesenchymal stromal cells (MSCs) have been investigated as a treatment for various inflammatory diseases because of their immunomodulatory and reparative properties. However, many basic questions concerning their mechanisms of action after systemic infusion remain unanswered. We performed a detailed analysis of the immunomodulatory properties and proteomic profile of MSCs systemically administered to two patients with severe refractory acute respiratory distress syndrome (ARDS) on a compassionate use basis and attempted to correlate these with in vivo anti-inflammatory actions. Both patients received 2 × 10(6) cells per kilogram, and each subsequently improved with resolution of respiratory, hemodynamic, and multiorgan failure. In parallel, a decrease was seen in multiple pulmonary and systemic markers of inflammation, including epithelial apoptosis, alveolar-capillary fluid leakage, and proinflammatory cytokines, microRNAs, and chemokines. In vitro studies of the MSCs demonstrated a broad anti-inflammatory capacity, including suppression of T-cell responses and induction of regulatory phenotypes in T cells, monocytes, and neutrophils. Some of these in vitro potency assessments correlated with, and were relevant to, the observed in vivo actions. These experiences highlight both the mechanistic information that can be gained from clinical experience and the value of correlating in vitro potency assessments with clinical effects. The findings also suggest, but do not prove, a beneficial effect of lung protective strategies using adoptively transferred MSCs in ARDS. Appropriate randomized clinical trials are required to further assess any potential clinical efficacy and investigate the effects on in vivo inflammation. SIGNIFICANCE: This article describes the cases of two patients with severe refractory adult respiratory syndrome (ARDS) who failed to improve after both standard life support measures, including mechanical ventilation, and additional measures, including extracorporeal ventilation (i.e., in a heart-lung machine). Unlike acute forms of ARDS (such in the current NIH-sponsored study of mesenchymal stromal cells in ARDS), recovery does not generally occur in such patients.",,"['Simonson, Oscar E.', 'Mougiakakos, Dimitrios', 'Heldring, Nina', 'Bassi, Giulio', 'Johansson, Henrik J.', 'Dalén, Magnus', 'Jitschin, Regina', 'Rodin, Sergey', 'Corbascio, Matthias', 'El Andaloussi, Samir', 'Wiklander, Oscar P.B.', 'Nordin, Joel Z.', 'Skog, Johan', 'Romain, Charlotte', 'Koestler, Tina', 'Hellgren-Johansson, Laila', 'Schiller, Petter', 'Joachimsson, Per-Olof', 'Hägglund, Hans', 'Mattsson, Mattias', 'Lehtiö, Janne', 'Faridani, Omid R.', 'Sandberg, Rickard', 'Korsgren, Olle', 'Krampera, Mauro', 'Weiss, Daniel J.', 'Grinnemo, Karl-Henrik', 'Le Blanc, Katarina']",,,,
,PMC,Long noncoding RNAs in innate immunity,http://dx.doi.org/10.1038/cmi.2015.68,PMC4786632,,,"Long noncoding RNAs (lncRNAs) have been shown to play important roles in immune cell development and immune responses through different mechanisms, such as dosage compensation, imprinting, enhancer function, and transcriptional regulation. Although the functions of most lncRNAs are unclear, some lncRNAs have been found to control transcriptional or post-transcriptional regulation of the innate and adaptive immune responses via new methods of protein–protein interactions or pairing with DNA and RNA. Interestingly, increasing evidence has elucidated the importance of lncRNAs in the interaction between hosts and pathogens. In this review, an overview of the lncRNAs modes of action, as well as the important and diversified roles of lncRNAs in immunity, are provided, and an emerging paradigm of lncRNAs in regulating innate immune responses is highlighted.",,"['Zhang, Yuan', 'Cao, Xuetao']",,,,
,PMC,Recent Advances in the Discovery of Norovirus Therapeutics: Miniperspective,http://dx.doi.org/10.1021/acs.jmedchem.5b00762,PMC5168802,,,"Noroviruses are members of the family Caliciviridae. Norovirus infections are a global health burden that impacts >20 million individuals annually in the U.S. alone. Noroviruses are associated with high morbidity among vulnerable populations, particularly immunocompromised patients. This perspective highlights recent developments related to the discovery and development of norovirus-specific small-molecule therapeutics as well as recent advances in our understanding of norovirus biology and pathogenesis. Most of the work in this area is at the early discovery stage and has been primarily focused on inhibitors of norovirus 3C-like protease and RNA dependent RNA polymerase. However, recent discoveries emanating from basic studies in norovirus research have resulted in the identification of new host-related drug targets that can be exploited. A repurposed compound has been advanced to human clinical studies.",,"['Kim, Yunjeong', 'Galasiti Kankanamalage, Anushka C.', 'Chang, Kyeong-Ok', 'Groutas, William C.']",,,,
,PMC,Inhibition of Aminoglycoside 6′-N-Acetyltransferase Type Ib-Mediated Amikacin Resistance in Klebsiella pneumoniae by Zinc and Copper Pyrithione,http://dx.doi.org/10.1128/AAC.01106-15,PMC4538519,,,"The in vitro activity of the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib] was inhibited by CuCl(2) with a 50% inhibitory concentration (IC(50)) of 2.8 μM. The growth of an amikacin-resistant Klebsiella pneumoniae strain isolated from a neonate with meningitis was inhibited when amikacin was supplemented by the addition of Zn(2+) or Cu(2+) in complex with the ionophore pyrithione. Coordination complexes between cations and ionophores could be developed for their use, in combination with aminoglycosides, to treat resistant infections.",,"['Chiem, Kevin', 'Fuentes, Brooke A.', 'Lin, David L.', 'Tran, Tung', 'Jackson, Alexis', 'Ramirez, Maria S.', 'Tolmasky, Marcelo E.']",,,,
,PMC,Kallistatin Ameliorates Influenza Virus Pathogenesis by Inhibition of Kallikrein-Related Peptidase 1-Mediated Cleavage of Viral Hemagglutinin,http://dx.doi.org/10.1128/AAC.00065-15,PMC4538499,,,"Proteolytic cleavage of the hemagglutinin (HA) of influenza virus by host trypsin-like proteases is required for viral infectivity. Some serine proteases are capable of cleaving influenza virus HA, whereas some serine protease inhibitors (serpins) inhibit the HA cleavage in various cell types. Kallikrein-related peptidase 1 (KLK1, also known as tissue kallikrein) is a widely distributed serine protease. Kallistatin, a serpin synthesized mainly in the liver and rapidly secreted into the circulation, forms complexes with KLK1 and inhibits its activity. Here, we investigated the roles of KLK1 and kallistatin in influenza virus infection. We show that the levels of KLK1 increased, whereas those of kallistatin decreased, in the lungs of mice during influenza virus infection. KLK1 cleaved H1, H2, and H3 HA molecules and consequently enhanced viral production. In contrast, kallistatin inhibited KLK1-mediated HA cleavage and reduced viral production. Cells transduced with the kallistatin gene secreted kallistatin extracellularly, which rendered them more resistant to influenza virus infection. Furthermore, lentivirus-mediated kallistatin gene delivery protected mice against lethal influenza virus challenge by reducing the viral load, inflammation, and injury in the lung. Taking the data together, we determined that KLK1 and kallistatin contribute to the pathogenesis of influenza virus by affecting the cleavage of the HA peptide and inflammatory responses. This study provides a proof of principle for the potential therapeutic application of kallistatin or other KLK1 inhibitors for influenza. Since proteolytic activation also enhances the infectivity of some other viruses, kallistatin and other kallikrein inhibitors may be explored as antiviral agents against these viruses.",,"['Leu, Chia-Hsing', 'Yang, Mei-Lin', 'Chung, Nai-Hui', 'Huang, Yen-Jang', 'Su, Yu-Chu', 'Chen, Yi-Cheng', 'Lin, Chia-Cheng', 'Shieh, Gia-Shing', 'Chang, Meng-Ya', 'Wang, Shainn-Wei', 'Chang, Yao', 'Chao, Julie', 'Chao, Lee', 'Wu, Chao-Liang', 'Shiau, Ai-Li']",,,,
,PMC,A Distinct Region in Erythropoietin that Induces Immuno/Inflammatory Modulation and Tissue Protection,http://dx.doi.org/10.1007/s13311-015-0379-1,PMC4604189,,,"Beneficial effects of short-term whole-molecule erythropoietin (EPO) therapy have been demonstrated on several animal models of diverse central nervous system pathology. However, the increased hematocrit induced by EPO-driven marrow stimulation greatly limits its potential for side effect-free therapy. We created a library of EPO-derived fragments based on the hypothesis that 2 distinct functions, erythropoiesis and tissue protection, reside in different regions of the molecule. Several small EPO-derived peptides within the Aβ loop of whole EPO molecule were screened for tissue protection in EAE mice. The 19-mer JM-4 peptide that contains 2 cysteine molecules consistently demonstrated the most potent clinical beneficial effects without producing hematocrit alterations in animal models of EAE. The JM-4-induced tissue protection was associated with modulation of the immunoregulatory process that drives inflammation and provokes subsequent autoimmune damage. Like the whole EPO molecule, JM-4 effectively modulated immune/inflammatory reaction within both the peripheral lymphatic tissue and central nervous system. The major effects induced by JM-4 include blocked expansion of monocyte/dendritic antigen presenting cell and T helper 17 cell populations, decreased proinflammatory cytokine production, and sharply enhanced expansion of the regulatory T-cell population. JM-4 shows promise for treatment of a broad spectrum of neural and non-neural conditions associated with inflammation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13311-015-0379-1) contains supplementary material, which is available to authorized users.",,"['Yuan, RuiRong', 'Wang, Bo', 'Lu, Wei', 'Maeda, Yasuhiro', 'Dowling, Peter']",,,,
,PMC,Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site,http://dx.doi.org/10.1016/j.cell.2015.07.043,PMC4757492,,,"Epstein-Barr virus (EBV) represents a major global health problem. Though it is associated with infectious mononucleosis and over 200,000 cancers annually worldwide, a vaccine is not available. The major target of immunity is EBV glycoprotein 350/220 (gp350) that mediates attachment to B cells through complement receptor 2 (CR2/CD21). Here, we created self-assembling nanoparticles that displayed different domains of gp350 in a symmetric array. By focusing presentation of the CR2-binding domain on nanoparticles, potent neutralizing antibodies were elicited in mice and non-human primates. The structurally designed nanoparticle vaccine improved vaccine-induced protection in a mouse model by targeting a functionally conserved site of vulnerability with 10- to 100-fold increased neutralization compared to soluble gp350. This rational approach to EBV vaccine design elicited potent neutralizing antibody responses by focusing on a conserved viral entry domain, a strategy that can be applied to other viruses.",,"['Kanekiyo, Masaru', 'Bu, Wei', 'Joyce, M. Gordon', 'Meng, Geng', 'Whittle, James R.R.', 'Baxa, Ulrich', 'Yamamoto, Takuya', 'Narpala, Sandeep', 'Todd, John-Paul', 'Rao, Srinivas S.', 'McDermott, Adrian B.', 'Koup, Richard A.', 'Rossmann, Michael G.', 'Mascola, John R.', 'Graham, Barney S.', 'Cohen, Jeffrey I.', 'Nabel, Gary J.']",,,,
,PMC,Public Health and Epidemiology Informatics: Recent Research and Trends in the United States,http://dx.doi.org/10.15265/IY-2015-012,PMC4587030,,,"OBJECTIVES: To survey advances in public health and epidemiology informatics over the past three years. METHODS: We conducted a review of English-language research works conducted in the domain of public health informatics (PHI), and published in MEDLINE between January 2012 and December 2014, where information and communication technology (ICT) was a primary subject, or a main component of the study methodology. Selected articles were synthesized using a thematic analysis using the Essential Services of Public Health as a typology. RESULTS: Based on themes that emerged, we organized the advances into a model where applications that support the Essential Services are, in turn, supported by a socio-technical infrastructure that relies on government policies and ethical principles. That infrastructure, in turn, depends upon education and training of the public health workforce, development that creates novel or adapts existing infrastructure, and research that evaluates the success of the infrastructure. Finally, the persistence and growth of infrastructure depends on financial sustainability. CONCLUSIONS: Public health informatics is a field that is growing in breadth, depth, and complexity. Several Essential Services have benefited from informatics, notably, “Monitor Health,” “Diagnose & Investigate,” and “Evaluate.” Yet many Essential Services still have not yet benefited from advances such as maturing electronic health record systems, interoperability amongst health information systems, analytics for population health management, use of social media among consumers, and educational certification in clinical informatics. There is much work to be done to further advance the science of PHI as well as its impact on public health practice.",,"['Dixon, B. E.', 'Kharrazi, H.', 'Lehmann, H. P.']",,,,
,PMC,"Outbreak column 18: The undervalued work of outbreak: prevention, preparedness, detection and management",http://dx.doi.org/10.1177/1757177415599592,PMC5074162,,,"There are oft-quoted studies which advise that between 1% and 10% of healthcare-associated infections (HAIs) present as healthcare-associated outbreaks (HAOs). Examination of these studies showed they lacked validity due to a low sensitivity to detect HAO, and because they pre-date both advanced healthcare systems and the emergence of recent nosocomial pathogen challenges. The accepted inference: that as there are so few HAOs the focus of surveillance programmes should be on endemic and not epidemic infections (outbreaks), is therefore called into question. Current estimates of HAI burden are derived from Point Prevalence Surveys (PPS) which are neither designed to nor are capable of detecting HAOs. We considered the extensive Infection Prevention and Control Team (IPCT) work to prevent and prepare for perennial and novel HAOs and suggest that at present this endeavour is largely unseen, underestimated and undervalued. Any HAI burden estimate needs to comprise a more complete HAI summary than PPS data. This can only be done with a more inclusive surveillance system that has a wider focus than just prevalent infections. There is a real risk of redirection of the IPCT resource from outbreak prevention and preparedness work towards HAI that are counted: such a change could only further increase HAO risks.",,"['Curran, Evonne T', 'Dalziel, Catherine E']",,,,
,PMC,Rhesus macaque θ-defensin RTD-1 inhibits proinflammatory cytokine secretion and gene expression by inhibiting the activation of NF-κB and MAPK pathways,http://dx.doi.org/10.1189/jlb.3A0315-102R,PMC4661038,,,"θ-Defensins are pleiotropic, macrocyclic peptides that are expressed uniquely in Old World monkeys. The peptides are potent, broad-spectrum microbicides that also modulate inflammatory responses in vitro and in animal models of viral infection and polymicrobial sepsis. θ-Defensins suppress proinflammatory cytokine secretion by leukocytes stimulated with diverse Toll-like receptor (TLR) ligands. Studies were performed to delineate anti-inflammatory mechanisms of rhesus θ-defensin 1 (RTD-1), the most abundant θ-defensin isoform in macaque granulocytes. RTD-1 reduced the secretion of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-8 in lipopolysaccharide (LPS)-stimulated human blood monocytes and THP-1 macrophages, and this was accompanied by inhibition of nuclear factor κB (NF-κB) activation and mitogen-activated protein kinase (MAPK) pathways. Peptide inhibition of NF-κB activation occurred following stimulation of extracellular (TLRs 1/2 and 4) and intracellular (TLR9) receptors. Although RTD-1 did not inhibit MAPK in unstimulated cells, it induced phosphorylation of Akt in otherwise untreated monocytes and THP-1 cells. In the latter, this occurred within 10 min of RTD-1 treatment and produced a sustained elevation of phosphorylated Akt (pAkt) for at least 4 h. pAkt is a negative regulator of MAPK and NF-κB activation. RTD-1 inhibited IκBα degradation and p38 MAPK phosphorylation, and stimulated Akt phosphorylation in LPS-treated human primary monocytes and THP-1 macrophages. Specific inhibition of phosphatidylinositol 3-kinase (PI3K) blocked RTD-1-stimulated Akt phosphorylation and reversed the suppression of NF-κB activation by the peptide. These studies indicate that the anti-inflammatory properties of θ-defensins are mediated by activation of the PI3K/Akt pathway and suppression of proinflammatory signals in immune-stimulated cells.",,"['Tongaonkar, Prasad', 'Trinh, Katie K.', 'Schaal, Justin B.', 'Tran, Dat', 'Gulko, Percio S.', 'Ouellette, André J.', 'Selsted, Michael E.']",,,,
,PMC,Increased Immune Response Variability during Simultaneous Viral Coinfection Leads to Unpredictability in CD8 T Cell Immunity and Pathogenesis,http://dx.doi.org/10.1128/JVI.01432-15,PMC4621125,,,"T cell memory is usually studied in the context of infection with a single pathogen in naive mice, but how memory develops during a coinfection with two pathogens, as frequently occurs in nature or after vaccination, is far less studied. Here, we questioned how the competition between immune responses to two viruses in the same naive host would influence the development of CD8 T cell memory and subsequent disease outcome upon challenge. Using two different models of coinfection, including the well-studied lymphocytic choriomeningitis (LCMV) and Pichinde (PICV) viruses, several differences were observed within the CD8 T cell responses to either virus. Compared to single-virus infection, coinfection resulted in substantial variation among mice in the size of epitope-specific T cell responses to each virus. Some mice had an overall reduced number of virus-specific cells to either one of the viruses, and other mice developed an immunodominant response to a normally subdominant, cross-reactive epitope (nucleoprotein residues 205 to 212, or NP205). These changes led to decreased protective immunity and enhanced pathology in some mice upon challenge with either of the original coinfecting viruses. In mice with PICV-dominant responses, during a high-dose challenge with LCMV clone 13, increased immunopathology was associated with a reduced number of LCMV-specific effector memory CD8 T cells. In mice with dominant cross-reactive memory responses, during challenge with PICV increased immunopathology was directly associated with these cross-reactive NP205-specific CD8 memory cells. In conclusion, the inherent competition between two simultaneous immune responses results in significant alterations in T cell immunity and subsequent disease outcome upon reexposure. IMPORTANCE Combination vaccines and simultaneous administration of vaccines are necessary to accommodate required immunizations and maintain vaccination rates. Antibody responses generally correlate with protection and vaccine efficacy. However, live attenuated vaccines also induce strong CD8 T cell responses, and the impact of these cells on subsequent immunity, whether beneficial or detrimental, has seldom been studied, in part due to the lack of known T cell epitopes to vaccine viruses. We questioned if the inherent increased competition and stochasticity between two immune responses during a simultaneous coinfection would significantly alter CD8 T cell memory in a mouse model where CD8 T cell epitopes are clearly defined. We show that some of the coinfected mice have sufficiently altered memory T cell responses that they have decreased protection and enhanced immunopathology when reexposed to one of the two viruses. These data suggest that a better understanding of human T cell responses to vaccines is needed to optimize immunization strategies.",,"['Kenney, Laurie L.', 'Cornberg, Markus', 'Chen, Alex T.', 'Emonet, Sebastien', 'de la Torre, Juan Carlos', 'Selin, Liisa K.']",,,,
,PMC,Severe Acute Respiratory Syndrome (SARS) Coronavirus ORF8 Protein Is Acquired from SARS-Related Coronavirus from Greater Horseshoe Bats through Recombination,http://dx.doi.org/10.1128/JVI.01048-15,PMC4580176,,,"Despite the identification of horseshoe bats as the reservoir of severe acute respiratory syndrome (SARS)-related coronaviruses (SARSr-CoVs), the origin of SARS-CoV ORF8, which contains the 29-nucleotide signature deletion among human strains, remains obscure. Although two SARS-related Rhinolophus sinicus bat CoVs (SARSr-Rs-BatCoVs) previously detected in Chinese horseshoe bats (Rhinolophus sinicus) in Yunnan, RsSHC014 and Rs3367, possessed 95% genome identities to human and civet SARSr-CoVs, their ORF8 protein exhibited only 32.2 to 33% amino acid identities to that of human/civet SARSr-CoVs. To elucidate the origin of SARS-CoV ORF8, we sampled 348 bats of various species in Yunnan, among which diverse alphacoronaviruses and betacoronaviruses, including potentially novel CoVs, were identified, with some showing potential interspecies transmission. The genomes of two betacoronaviruses, SARSr-Rf-BatCoV YNLF_31C and YNLF_34C, from greater horseshoe bats (Rhinolophus ferrumequinum), possessed 93% nucleotide identities to human/civet SARSr-CoV genomes. Although these two betacoronaviruses displayed lower similarities than SARSr-Rs-BatCoV RsSHC014 and Rs3367 in S protein to civet SARSr-CoVs, their ORF8 proteins demonstrated exceptionally high (80.4 to 81.3%) amino acid identities to that of human/civet SARSr-CoVs, compared to SARSr-BatCoVs from other horseshoe bats (23.2 to 37.3%). Potential recombination events were identified around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. The expression of ORF8 subgenomic mRNA suggested that the ORF8 protein may be functional in SARSr-Rf-BatCoVs. The high K(a)/K(s) ratio among human SARS-CoVs compared to that among SARSr-BatCoVs supported that ORF8 is under strong positive selection during animal-to-human transmission. Molecular clock analysis using ORF1ab showed that SARSr-Rf-BatCoV YNLF_31C and YNLF_34C diverged from civet/human SARSr-CoVs in approximately 1990. SARS-CoV ORF8 originated from SARSr-CoVs of greater horseshoe bats through recombination, which may be important for animal-to-human transmission. IMPORTANCE Although horseshoe bats are the primary reservoir of SARS-related coronaviruses (SARSr-CoVs), it is still unclear how these bat viruses have evolved to cross the species barrier to infect civets and humans. Most human SARS-CoV epidemic strains contain a signature 29-nucleotide deletion in ORF8, compared to civet SARSr-CoVs, suggesting that ORF8 may be important for interspecies transmission. However, the origin of SARS-CoV ORF8 remains obscure. In particular, SARSr-Rs-BatCoVs from Chinese horseshoe bats (Rhinolophus sinicus) exhibited <40% amino acid identities to human/civet SARS-CoV in the ORF8 protein. We detected diverse alphacoronaviruses and betacoronaviruses among various bat species in Yunnan, China, including two SARSr-Rf-BatCoVs from greater horseshoe bats that possessed ORF8 proteins with exceptionally high amino acid identities to that of human/civet SARSr-CoVs. We demonstrated recombination events around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. Our findings offer insight into the evolutionary origin of SARS-CoV ORF8 protein, which was likely acquired from SARSr-CoVs of greater horseshoe bats through recombination.",,"['Lau, Susanna K. P.', 'Feng, Yun', 'Chen, Honglin', 'Luk, Hayes K. H.', 'Yang, Wei-Hong', 'Li, Kenneth S. M.', 'Zhang, Yu-Zhen', 'Huang, Yi', 'Song, Zhi-Zhong', 'Chow, Wang-Ngai', 'Fan, Rachel Y. Y.', 'Ahmed, Syed Shakeel', 'Yeung, Hazel C.', 'Lam, Carol S. F.', 'Cai, Jian-Piao', 'Wong, Samson S. Y.', 'Chan, Jasper F. W.', 'Yuen, Kwok-Yung', 'Zhang, Hai-Lin', 'Woo, Patrick C. Y.']",,,,
,PMC,Replication-Competent Controlled Herpes Simplex Virus,http://dx.doi.org/10.1128/JVI.01667-15,PMC4580158,,,"We present the development and characterization of a replication-competent controlled herpes simplex virus 1 (HSV-1). Replication-essential ICP4 and ICP8 genes of HSV-1 wild-type strain 17syn+ were brought under the control of a dually responsive gene switch. The gene switch comprises (i) a transactivator that is activated by a narrow class of antiprogestins, including mifepristone and ulipristal, and whose expression is mediated by a promoter cassette that comprises an HSP70B promoter and a transactivator-responsive promoter and (ii) transactivator-responsive promoters that drive the ICP4 and ICP8 genes. Single-step growth experiments in different cell lines demonstrated that replication of the recombinant virus, HSV-GS3, is strictly dependent on an activating treatment consisting of administration of a supraphysiological heat dose in the presence of an antiprogestin. The replication-competent controlled virus replicates with an efficiency approaching that of the wild-type virus from which it was derived. Essentially no replication occurs in the absence of activating treatment or if HSV-GS3-infected cells are exposed only to heat or antiprogestin. These findings were corroborated by measurements of amounts of viral DNA and transcripts of the regulated ICP4 gene and the glycoprotein C (gC) late gene, which was not regulated. Similar findings were made in experiments with a mouse footpad infection model. IMPORTANCE The alphaherpesviruses have long been considered vectors for recombinant vaccines and oncolytic therapies. The traditional approach uses vector backbones containing attenuating mutations that restrict replication to ensure safety. The shortcoming of this approach is that the attenuating mutations tend to limit both the immune presentation and oncolytic properties of these vectors. HSV-GS3 represents a novel type of vector that, when activated, replicates with the efficiency of a nonattenuated virus and whose safety is derived from deliberate, stringent regulation of multiple replication-essential genes. By directing activating heat to the region of virus administration, replication is strictly confined to infected cells within this region. The requirement for antiprogestin provides an additional level of safety, ensuring that virus replication cannot be triggered inadvertently. Replication-competent controlled vectors such as HSV-GS3 may have the potential to be superior to conventional attenuated HSV vaccine and oncolytic vectors without sacrificing safety.",,"['Bloom, David C.', 'Feller, Joyce', 'McAnany, Peterjon', 'Vilaboa, Nuria', 'Voellmy, Richard']",,,,
,PMC,Next-generation sequencing in clinical virology: Discovery of new viruses,http://dx.doi.org/10.5501/wjv.v4.i3.265,PMC4534817,,,"Viruses are a cause of significant health problem worldwide, especially in the developing nations. Due to different anthropological activities, human populations are exposed to different viral pathogens, many of which emerge as outbreaks. In such situations, discovery of novel viruses is utmost important for deciding prevention and treatment strategies. Since last century, a number of different virus discovery methods, based on cell culture inoculation, sequence-independent PCR have been used for identification of a variety of viruses. However, the recent emergence and commercial availability of next-generation sequencers (NGS) has entirely changed the field of virus discovery. These massively parallel sequencing platforms can sequence a mixture of genetic materials from a very heterogeneous mix, with high sensitivity. Moreover, these platforms work in a sequence-independent manner, making them ideal tools for virus discovery. However, for their application in clinics, sample preparation or enrichment is necessary to detect low abundance virus populations. A number of techniques have also been developed for enrichment or viral nucleic acids. In this manuscript, we review the evolution of sequencing; NGS technologies available today as well as widely used virus enrichment technologies. We also discuss the challenges associated with their applications in the clinical virus discovery.",,"['Datta, Sibnarayan', 'Budhauliya, Raghvendra', 'Das, Bidisha', 'Chatterjee, Soumya', 'Vanlalhmuaka,', 'Veer, Vijay']",,,,
,PMC,Middle-East respiratory syndrome coronavirus: Is it worth a world panic?,http://dx.doi.org/10.5501/wjv.v4.i3.185,PMC4534810,,,"In 2012 Middle-East respiratory syndrome coronavirus (MERS-CoV) was evolved in the Arabian Peninsula. Tremendous and successful efforts have been conducted to discover the genome structure, epidemiology, clinical signs, pathogenesis, diagnosis and antiviral therapy. Taphozous perforatus bats are the incriminated reservoir host and camels are the currently confirmed animal linker. The virus resulted in less than 1000 infected cases and 355 deaths. The case fatality rate of the MERS-CoV is high, however, many survivors of MERS-CoV infection showed inapparent infections and, in several cases, multiple co-infecting agents did exist. Although MERS-CoV appears to be a dangerous disease, it is argued here that a full assessment of current knowledge about the disease does not suggest that it is a truly scary killer.",,"Abdel-Moneim, Ahmed S",,,,
,PMC,Intranasal vaccination of recombinant H5N1 HA1 proteins fused with foldon and Fc induces strong mucosal immune responses with neutralizing activity: Implication for developing novel mucosal influenza vaccines,http://dx.doi.org/10.1080/21645515.2015.1074363,PMC5054784,,,"The highly pathogenic avian influenza (HPAI) H5N1 virus remains a threat to public health because of its continued spread in poultry in some countries and its ability to infect humans with high mortality rate, calling for the development of effective and safe vaccines against H5N1 infection. Here, we constructed 4 candidate vaccines by fusing H5N1 hemagglutinin 1 (HA1) with foldon (HA1-Fd), human IgG Fc (HA1-Fc), foldon and Fc (HA1-FdFc) or His-tag (HA1-His). We then compared their ability to induce mucosal immune responses and neutralizing antibodies in the presence or absence of Poly(I:C) and CpG adjuvants via the intranasal route. Without an adjuvant, HA1-FdFc could elicit appreciable humoral immune responses and local mucosal IgA antibodies in immunized mice, while other vaccine candidates only induced background immune responses. In the presence of Poly(I:C) and CpG, both HA1-Fd and HA1-Fc elicited much higher levels of serum IgG and local mucosal IgA antibodies than HA1-His. Poly(I:C) and CpG could also augment the neutralizing antibody responses induced by these 4 vaccine candidates in the order of HA1-FdFc > HA1-Fc > HA1-Fd > HA1-His. These results suggest that both Fd and Fc potentiate the immunogenicity of the recombinant HA1 protein and that Poly(I:C) and CpG serve as efficient mucosal adjuvants in promoting efficacy of these vaccine candidates to induce strong systemic and local antibody responses and potent neutralizing antibodies, providing a useful strategy to develop effective and safe mucosal H5N1 vaccines.",,"['Yu, Fei', 'Li, Ye', 'Guo, Yan', 'Wang, Lili', 'Yang, Jie', 'Zhao, Guangyu', 'Zhou, Yusen', 'Du, Lanying', 'Jiang, Shibo']",,,,
,PMC,Human Vaccines and Immunotherapeutics: News,http://dx.doi.org/10.1080/21645515.2015.1068540,PMC4635897,,,,,,,,,
,PMC,Deciphering the bat virome catalog to better understand the ecological diversity of bat viruses and the bat origin of emerging infectious diseases,http://dx.doi.org/10.1038/ismej.2015.138,PMC4817686,,,"Studies have demonstrated that ~60%–80% of emerging infectious diseases (EIDs) in humans originated from wild life. Bats are natural reservoirs of a large variety of viruses, including many important zoonotic viruses that cause severe diseases in humans and domestic animals. However, the understanding of the viral population and the ecological diversity residing in bat populations is unclear, which complicates the determination of the origins of certain EIDs. Here, using bats as a typical wildlife reservoir model, virome analysis was conducted based on pharyngeal and anal swab samples of 4440 bat individuals of 40 major bat species throughout China. The purpose of this study was to survey the ecological and biological diversities of viruses residing in these bat species, to investigate the presence of potential bat-borne zoonotic viruses and to evaluate the impacts of these viruses on public health. The data obtained in this study revealed an overview of the viral community present in these bat samples. Many novel bat viruses were reported for the first time and some bat viruses closely related to known human or animal pathogens were identified. This genetic evidence provides new clues in the search for the origin or evolution pattern of certain viruses, such as coronaviruses and noroviruses. These data offer meaningful ecological information for predicting and tracing wildlife-originated EIDs.",,"['Wu, Zhiqiang', 'Yang, Li', 'Ren, Xianwen', 'He, Guimei', 'Zhang, Junpeng', 'Yang, Jian', 'Qian, Zhaohui', 'Dong, Jie', 'Sun, Lilian', 'Zhu, Yafang', 'Du, Jiang', 'Yang, Fan', 'Zhang, Shuyi', 'Jin, Qi']",,,,
,PMC,A molecular trigger for intercontinental epidemics of group A Streptococcus,http://dx.doi.org/10.1172/JCI82478,PMC4588293,,,"The identification of the molecular events responsible for strain emergence, enhanced virulence, and epidemicity has been a long-pursued goal in infectious diseases research. A recent analysis of 3,615 genomes of serotype M1 group A Streptococcus strains (the so-called “flesh-eating” bacterium) identified a recombination event that coincides with the global M1 pandemic beginning in the early 1980s. Here, we have shown that the allelic variation that results from this recombination event, which replaces the chromosomal region encoding secreted NADase and streptolysin O, is the key driver of increased toxin production and enhanced infection severity of the M1 pandemic strains. Using isoallelic mutant strains, we found that 3 polymorphisms in this toxin gene region increase resistance to killing by human polymorphonuclear leukocytes, increase bacterial proliferation, and increase virulence in animal models of pharyngitis and necrotizing fasciitis. Genome sequencing of an additional 1,125 streptococcal strains and virulence studies revealed that a highly similar recombinational replacement event underlies an ongoing intercontinental epidemic of serotype M89 group A Streptococcus infections. By identifying the molecular changes that enhance upper respiratory tract fitness, increased resistance to innate immunity, and increased tissue destruction, we describe a mechanism that underpins epidemic streptococcal infections, which have affected many millions of people.",,"['Zhu, Luchang', 'Olsen, Randall J.', 'Nasser, Waleed', 'Beres, Stephen B.', 'Vuopio, Jaana', 'Kristinsson, Karl G.', 'Gottfredsson, Magnus', 'Porter, Adeline R.', 'DeLeo, Frank R.', 'Musser, James M.']",,,,
,PMC,Swift antibodies to counter emerging viruses,http://dx.doi.org/10.1073/pnas.1513050112,PMC4547222,,,,,"['Burton, Dennis R.', 'Saphire, Erica Ollmann']",,,,
,PMC,Dromedary camels and the transmission of Middle East Respiratory Syndrome Coronavirus (MERS-CoV),http://dx.doi.org/10.1111/tbed.12401,PMC4749478,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) is an existential threat to global public health. The virus has been repeatedly detected in dromedary camels (Camelus dromedarius). Adult animals in many countries in the Middle East as well as in North and East Africa showed high (>90%) sero-prevalence to the virus. MERS-CoV isolated from dromedaries is genetically and phenotypically similar to viruses from humans. We summarise current understanding of the ecology of MERS-CoV in animals and transmission at the animal-human interface. We review aspects of husbandry, animal movements and trade and the use and consumption of camel dairy and meat products in the Middle East that may be relevant to the epidemiology of MERS. We also highlight the gaps in understanding the transmission of this virus in animals and from animals to humans.",,"['Hemida, Maged G', 'Elmoslemany, Ahmed', 'Al-Hizab, Fahad', 'Alnaeem, Abdulmohsen', 'Almathen, Faisal', 'Faye, Bernard', 'Chu, Daniel KW', 'Perera, Ranawaka A', 'Peiris, Malik']",,,,
,PMC,Preventing stem cell transplantation-associated viral infections using T-cell therapy,http://dx.doi.org/10.2217/imt.15.43,PMC4575639,,,"Hematopoietic stem cell transplantation is the treatment of choice for many hematologic malignancies and genetic diseases. However, viral infections continue to account for substantial post-transplant morbidity and mortality. While antiviral drugs are available against some viruses, they are associated with significant side effects and are frequently ineffective. This review focuses on the immunotherapeutic strategies that have been used to prevent and treat infections over the past 20 years and outlines different refinements that have been introduced with the goal of moving this therapy beyond specialized academic centers.",,"['Tzannou, Ifigeneia', 'Leen, Ann M']",,,,
,PMC,Middle East respiratory syndrome in the Republic of Korea: transparency and communication are key,http://dx.doi.org/10.5365/WPSAR.2015.6.2.011,PMC4675162,,,,,"['Fung, Isaac Chun-Hai', 'Tse, Zion Tsz Ho', 'Chan, Benedict Shing Bun', 'Fu, King-Wa']",,,,
,PMC,Balancing the Duty to Treat Patients with Ebola Virus Disease with the Risks to Dialysis Personnel,http://dx.doi.org/10.2215/CJN.03730415,PMC4670767,,,"In 2014, the author was invited to present at the American Society for Nephrology’s annual conference in Philadelphia on the ethics of treating patients with Ebola virus disease. The argument was made that the status of health care workers, including nephrologists, was the dominant ethical standard that generated both the duty to treat and the conflicts between this commitment and other ethical commitments that arise in public health emergencies. Conflicts between duty to treat and personal safety, duty to community, and duty to colleagues were illustrated, and suggestions for designing ethics into medical practice were given. This article is a summary of that presentation.",,"Evans, Nicholas G.",,,,
,PMC,Hospitalizations and Outpatient Visits for Rhinovirus - Associated Acute Respiratory Illness in Adults,http://dx.doi.org/10.1016/j.jaci.2015.06.017,PMC4744574,,,"BACKGROUND: Rhinovirus is linked to asthma exacerbations and chronic obstructive pulmonary disease exacerbations in adults. The severity and rates of rhinovirus acute respiratory illnesses (ARI) in adults are uncertain. OBJECTIVES: We determined rhinovirus-associated ARI rates in adults presenting for care in multiple settings and identified factors associated with rhinovirus detection. METHODS: This prospective, population-based cohort enrolled Tennessee residents ≥18 years old in the emergency department (ED), outpatient clinics, or hospitalized for ARI December 2008-May 2010. Nasal/throat swabs were collected and tested for rhinovirus and other viruses by RT-PCR. Rates of ED visits and hospitalizations were calculated and rhinovirus-positive and -negative patients were compared. RESULTS: Among 2351 enrollees, rhinovirus was detected in 247 (11%). There were 7 rhinovirus-associated ED visits and 3 hospitalizations per 1000 adults annually. Patients with rhinovirus, compared to virus-negative ARI, were more likely to present with wheezing (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.23-2.35, p<0.001), to be a current smoker (OR 2.31, CI 1.68-3.19) or live with a smoker (OR 1.72, CI 1.10-2.67), have a history of chronic respiratory disease (OR 1.61, CI 1.17-2.22), and were less likely to be hospitalized versus seen in the outpatient setting (OR 0.58, CI 0.41-0.83). CONCLUSION: Rhinovirus is associated with a substantial number of ED visits and hospitalizations for ARI in adults. There may be modifiable factors that can reduce the likelihood of presenting with rhinovirus-associated ARI.",,"['Miller, E. Kathryn', 'Linder, Jodell', 'Kraft, David', 'Johnson, Monika', 'Lu, Pengcheng', 'Saville, Benjamin R.', 'Williams, John V.', 'Griffin, Marie R.', 'Talbot, H. Keipp']",,,,
,PMC,Evidence of Hantavirus Infection among Bats in Brazil,http://dx.doi.org/10.4269/ajtmh.15-0032,PMC4530771,,,"Hantaviruses are zoonotic viruses harbored by rodents, bats, and shrews. At present, only rodent-borne hantaviruses are associated with severe illness in humans. New species of hantaviruses have been recently identified in bats and shrews greatly expanding the potential reservoirs and ranges of these viruses. Brazil has one of the highest incidences of hantavirus cardiopulmonary syndrome in South America, hence it is critical to know what is the prevalence of hantaviruses in Brazil. Although much is known about rodent reservoirs, little is known regarding bats. We captured 270 bats from February 2012 to April 2014. Serum was screened for the presence of antibodies against a recombinant nucleoprotein (rN) of Araraquara virus (ARAQV). The prevalence of antibody to hantavirus was 9/53 with an overall seroprevalence of 17%. Previous studies have shown only insectivorous bats to harbor hantavirus; however, in our study, of the nine seropositive bats, five were frugivorous, one was carnivorous, and three were sanguivorous phyllostomid bats.",,"['Sabino-Santos, Gilberto', 'Maia, Felipe Gonçalves Motta', 'Vieira, Thallyta Maria', 'de Lara Muylaert, Renata', 'Lima, Sabrina Miranda', 'Gonçalves, Cristieli Barros', 'Barroso, Patricia Doerl', 'Melo, Maria Norma', 'Jonsson, Colleen B.', 'Goodin, Douglas', 'Salazar-Bravo, Jorge', 'Figueiredo, Luiz Tadeu Moraes']",,,,
,PMC,Identification of Host Cell Factors Associated with Astrovirus Replication in Caco-2 Cells,http://dx.doi.org/10.1128/JVI.01225-15,PMC4580174,,,"Astroviruses are small, nonenveloped viruses with a single-stranded positive-sense RNA genome causing acute gastroenteritis in children and immunocompromised patients. Since positive-sense RNA viruses have frequently been found to replicate in association with membranous structures, in this work we characterized the replication of the human astrovirus serotype 8 strain Yuc8 in Caco-2 cells, using density gradient centrifugation and free-flow zonal electrophoresis (FFZE) to fractionate cellular membranes. Structural and nonstructural viral proteins, positive- and negative-sense viral RNA, and infectious virus particles were found to be associated with a distinct population of membranes separated by FFZE. The cellular proteins associated with this membrane population in infected and mock-infected cells were identified by tandem mass spectrometry. The results indicated that membranes derived from multiple cell organelles were present in the population. Gene ontology and protein-protein interaction network analysis showed that groups of proteins with roles in fatty acid synthesis and ATP biosynthesis were highly enriched in the fractions of this population in infected cells. Based on this information, we investigated by RNA interference the role that some of the identified proteins might have in the replication cycle of the virus. Silencing of the expression of genes involved in cholesterol (DHCR7, CYP51A1) and fatty acid (FASN) synthesis, phosphatidylinositol (PI4KIIIβ) and inositol phosphate (ITPR3) metabolism, and RNA helicase activity (DDX23) significantly decreased the amounts of Yuc8 genomic and antigenomic RNA, synthesis of the structural protein VP90, and virus yield. These results strongly suggest that astrovirus RNA replication and particle assembly take place in association with modified membranes potentially derived from multiple cell organelles. IMPORTANCE Astroviruses are common etiological agents of acute gastroenteritis in children and immunocompromised patients. More recently, they have been associated with neurological diseases in mammals, including humans, and are also responsible for different pathologies in birds. In this work, we provide evidence that astrovirus RNA replication and virus assembly occur in contact with cell membranes potentially derived from multiple cell organelles and show that membrane-associated cellular proteins involved in lipid metabolism are required for efficient viral replication. Our findings provide information to enhance our knowledge of astrovirus biology and provide information that might be useful for the development of therapeutic interventions to prevent virus replication.",,"['Murillo, Andrea', 'Vera-Estrella, Rosario', 'Barkla, Bronwyn J.', 'Méndez, Ernesto', 'Arias, Carlos F.']",,,,
,PMC,Neuraminidase of Influenza A Virus Binds Lysosome-Associated Membrane Proteins Directly and Induces Lysosome Rupture,http://dx.doi.org/10.1128/JVI.01411-15,PMC4580162,,,"As a recycling center, lysosomes are filled with numerous acid hydrolase enzymes that break down waste materials and invading pathogens. Recently, lysosomal cell death has been defined as “lysosomal membrane permeabilization and the consequent leakage of lysosome contents into cytosol.” Here, we show that the neuraminidase (NA) of H5N1 influenza A virus markedly deglycosylates and degrades lysosome-associated membrane proteins (LAMPs; the most abundant membrane proteins of lysosome), which induces lysosomal rupture, and finally leads to cell death of alveolar epithelial carcinoma A549 cells and human tracheal epithelial cells. The NA inhibitors peramivir and zanamivir could effectively block the deglycosylation of LAMPs, inhibit the virus cell entry, and prevent cell death induced by the H5N1 influenza virus. The NA of seasonal H1N1 virus, however, does not share these characteristics. Our findings not only reveal a novel role of NA in the early stage of the H5N1 influenza virus life cycle but also elucidate the molecular mechanism of lysosomal rupture crucial for influenza virus induced cell death. IMPORTANCE The integrity of lysosomes is vital for maintaining cell homeostasis, cellular defense and clearance of invading pathogens. This study shows that the H5N1 influenza virus could induce lysosomal rupture through deglycosylating lysosome-associated membrane proteins (LAMPs) mediated by the neuraminidase activity of NA protein. NA inhibitors such as peramivir and zanamivir could inhibit the deglycosylation of LAMPs and protect lysosomes, which also further interferes with the H5N1 influenza virus infection at early stage of life cycle. This work is significant because it presents new concepts for NA's function, as well as for influenza inhibitors' mechanism of action, and could partially explain the high mortality and high viral load after H5N1 virus infection in human beings and why NA inhibitors have more potent therapeutic effects for lethal avian influenza virus infections at early stage.",,"['Ju, Xiangwu', 'Yan, Yiwu', 'Liu, Qiang', 'Li, Ning', 'Sheng, Miaomiao', 'Zhang, Lifang', 'Li, Xiao', 'Liang, Zhu', 'Huang, Fengming', 'Liu, Kangtai', 'Zhao, Yan', 'Zhang, Yanxu', 'Zou, Zhen', 'Du, Jianchao', 'Zhong, Ying', 'Zhou, Huandi', 'Yang, Peng', 'Lu, Huijun', 'Tian, Mingyao', 'Li, Dangsheng', 'Zhang, Jianming', 'Jin, Ningyi', 'Jiang, Chengyu']",,,,
,PMC,Hepatitis C Virus Envelope Glycoprotein E1 Forms Trimers at the Surface of the Virion,http://dx.doi.org/10.1128/JVI.00991-15,PMC4580159,,,"In hepatitis C virus (HCV)-infected cells, the envelope glycoproteins E1 and E2 assemble as a heterodimer. To investigate potential changes in the oligomerization of virion-associated envelope proteins, we performed SDS-PAGE under reducing conditions but without thermal denaturation. This revealed the presence of SDS-resistant trimers of E1 in the context of cell-cultured HCV (HCVcc) as well as in the context of HCV pseudoparticles (HCVpp). The formation of E1 trimers was found to depend on the coexpression of E2. To further understand the origin of E1 trimer formation, we coexpressed in bacteria the transmembrane (TM) domains of E1 (TME1) and E2 (TME2) fused to reporter proteins and analyzed the fusion proteins by SDS-PAGE and Western blotting. As expected for strongly interacting TM domains, TME1–TME2 heterodimers resistant to SDS were observed. These analyses also revealed homodimers and homotrimers of TME1, indicating that such complexes are stable species. The N-terminal segment of TME1 exhibits a highly conserved GxxxG sequence, a motif that is well documented to be involved in intramembrane protein-protein interactions. Single or double mutations of the glycine residues (Gly354 and Gly358) in this motif markedly decreased or abrogated the formation of TME1 homotrimers in bacteria, as well as homotrimers of E1 in both HCVpp and HCVcc systems. A concomitant loss of infectivity was observed, indicating that the trimeric form of E1 is essential for virus infectivity. Taken together, these results indicate that E1E2 heterodimers form trimers on HCV particles, and they support the hypothesis that E1 could be a fusion protein. IMPORTANCE HCV glycoproteins E1 and E2 play an essential role in virus entry into liver cells as well as in virion morphogenesis. In infected cells, these two proteins form a complex in which E2 interacts with cellular receptors, whereas the function of E1 remains poorly understood. However, recent structural data suggest that E1 could be the protein responsible for the process of fusion between viral and cellular membranes. Here we investigated the oligomeric state of HCV envelope glycoproteins. We demonstrate that E1 forms functional trimers after virion assembly and that in addition to the requirement for E2, a determinant for this oligomerization is present in a conserved GxxxG motif located within the E1 transmembrane domain. Taken together, these results indicate that a rearrangement of E1E2 heterodimer complexes likely occurs during the assembly of HCV particles to yield a trimeric form of the E1E2 heterodimer. Gaining structural information on this trimer will be helpful for the design of an anti-HCV vaccine.",,"['Falson, Pierre', 'Bartosch, Birke', 'Alsaleh, Khaled', 'Tews, Birke Andrea', 'Loquet, Antoine', 'Ciczora, Yann', 'Riva, Laura', 'Montigny, Cédric', 'Montpellier, Claire', 'Duverlie, Gilles', 'Pécheur, Eve-Isabelle', 'le Maire, Marc', 'Cosset, François-Loïc', 'Dubuisson, Jean', 'Penin, François']",,,,
,PMC,Automated identification of abnormal respiratory ciliary motion in nasal biopsies,http://dx.doi.org/10.1126/scitranslmed.aaa1233,PMC4972186,,,"Motile cilia lining the nasal and bronchial passages beat synchronously to clear mucus and foreign matter from the respiratory tract. This mucociliary defense mechanism is essential for pulmonary health, because respiratory ciliary motion defects, such as those in patients with primary ciliary dyskinesia (PCD) or congenital heart disease, can cause severe sinopulmonary disease necessitating organ transplant. The visual examination of nasal or bronchial biopsies is critical for the diagnosis of ciliary motion defects, but these analyses are highly subjective and error-prone. Although ciliary beat frequency can be computed, this metric cannot sensitively characterize ciliary motion defects. Furthermore, PCD can present without any ultrastructural defects, limiting the use of other detection methods, such as electron microscopy. Therefore, an unbiased, computational method for analyzing ciliary motion is clinically compelling. We present a computational pipeline using algorithms from computer vision and machine learning to decompose ciliary motion into quantitative elemental components. Using this framework, we constructed digital signatures for ciliary motion recognition and quantified specific properties of the ciliary motion that allowed high-throughput classification of ciliary motion as normal or abnormal. We achieved >90% classification accuracy in two independent data cohorts composed of patients with congenital heart disease, PCD, or heterotaxy, as well as healthy controls. Clinicians without specialized knowledge in machine learning or computer vision can operate this pipeline as a “black box” toolkit to evaluate ciliary motion.",,"['Quinn, Shannon P.', 'Zahid, Maliha J.', 'Durkin, John R.', 'Francis, Richard J.', 'Lo, Cecilia W.', 'Chennubhotla, S. Chakra']",,,,
,PMC,Community Surveillance of Respiratory Viruses Among Families in the Utah Better Identification of Germs-Longitudinal Viral Epidemiology (BIG-LoVE) Study,http://dx.doi.org/10.1093/cid/civ486,PMC4583580,,,"Background. This study: (1) describes the viral etiology of respiratory illness by prospectively collecting weekly symptom diaries and nasal swabs from families for 1 year, (2) analyzed data by reported symptoms, virus, age, and family composition, and (3) evaluated the duration of virus detection. Methods. Twenty-six households (108 individuals) provided concurrent symptom and nasal swab data for 4166 person-weeks. The FilmArray polymerase chain reaction (PCR) platform (BioFire Diagnostics, LLC) was used to detect 16 respiratory viruses. Viral illnesses were defined as ≥1 consecutive weeks with the same virus detected with symptoms reported in ≥1 week. Results. Participants reported symptoms in 23% and a virus was detected in 26% of person-weeks. Children younger than 5 years reported symptoms more often and were more likely to have a virus detected than older participants (odds ratio [OR] 2.47, 95% confidence interval [CI], 2.08–2.94 and OR 3.96, 95% CI, 3.35–4.70, respectively). Compared with single person households, individuals living with children experienced 3 additional weeks of virus detection. There were 783 viral detection episodes; 440 (56%) associated with symptoms. Coronaviruses, human metapneumovirus, and influenza A detections were usually symptomatic; bocavirus and rhinovirus detections were often asymptomatic. The mean duration of PCR detection was ≤2 weeks for all viruses and detections of ≥3 weeks occurred in 16% of episodes. Younger children had longer durations of PCR detection. Conclusions. Viral detection is often asymptomatic and occasionally prolonged, especially for bocavirus and rhinovirus. In clinical settings, the interpretation of positive PCR tests, particularly in young children and those who live with them, may be confounded.",,"['Byington, Carrie L.', 'Ampofo, Krow', 'Stockmann, Chris', 'Adler, Frederick R.', 'Herbener, Amy', 'Miller, Trent', 'Sheng, Xiaoming', 'Blaschke, Anne J.', 'Crisp, Robert', 'Pavia, Andrew T.']",,,,
,PMC,Anti-infective immunoadhesins from plants,http://dx.doi.org/10.1111/pbi.12441,PMC4749143,,,"Immunoadhesins are recombinant proteins that combine the ligand-binding region of a receptor or adhesion molecule with immunoglobulin constant domains. All FDA-approved immunoadhesins are designed to modulate the interaction of a human receptor with its normal ligand, such as Etanercept (Enbrel(®)), which interferes with the binding of tumour necrosis factor (TNF) to the TNF-alpha receptor and is used to treat inflammatory diseases such as rheumatoid arthritis. Like antibodies, immunoadhesins have long circulating half-lives, are readily purified by affinity-based methods and have the avidity advantages conferred by bivalency. Immunoadhesins that incorporate normal cellular receptors for viruses or bacterial toxins hold great, but as yet unrealized, potential for treating infectious disease. As decoy receptors, immunoadhesins have potential advantages over pathogen-targeted monoclonal antibodies. Planet Biotechnology has specialized in developing anti-infective immunoadhesins using plant expression systems. An immunoadhesin incorporating the cellular receptor for anthrax toxin, CMG2, potently blocks toxin activity in vitro and protects animals against inhalational anthrax. An immunoadhesin based on the receptor for human rhinovirus, ICAM-1, potently blocks infection of human cells by one of the major causes of the common cold. An immunoadhesin targeting the MERS coronavirus is in an early stage of development. We describe here the unique challenges involved in designing and developing immunoadhesins targeting infectious diseases in the hope of inspiring further research into this promising class of drugs.",,"['Wycoff, Keith', 'Maclean, James', 'Belle, Archana', 'Yu, Lloyd', 'Tran, Y', 'Roy, Chad', 'Hayden, Frederick']",,,,
,PMC,From bronchiolitis guideline to practice: A critical care perspective,http://dx.doi.org/10.5492/wjccm.v4.i3.152,PMC4524812,,,"Acute viral bronchiolitis is a leading cause of admission to pediatric intensive care units, but research on the care of these critically ill infants has been limited. Pathology of viral bronchiolitis revealed respiratory obstruction due to intraluminal debris and edema of the airways and vasculature. This and clinical evidence suggest that airway clearance interventions such as hypertonic saline nebulizers and pulmonary toilet devices may be of benefit, particularly in situations of atelectasis associated with bronchiolitis. Research to distinguish an underlying asthma predisposition in wheezing infants with viral bronchiolitis may one day lead to guidance on when to trial bronchodilator therapy. Considering the paucity of critical care research in pediatric viral bronchiolitis, intensive care practitioners must substantially rely on individualization of therapies based on bedside clinical assessments. However, with the introduction of new diagnostic and respiratory technologies, our ability to support critically ill infants with acute viral bronchiolitis will continue to advance.",,"['Lin, James A', 'Madikians, Andranik']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.01687-15,PMC4524068,,,,,,,,,
,PMC,Enhancing Syndromic Surveillance With Online Respondent-Driven Detection,http://dx.doi.org/10.2105/AJPH.2015.302717,PMC4504273,,,"Objectives. We investigated the feasibility of combining an online chain recruitment method (respondent-driven detection) and participatory surveillance panels to collect previously undetected information on infectious diseases via social networks of participants. Methods. In 2014, volunteers from 2 large panels in the Netherlands were invited to complete a survey focusing on symptoms of upper respiratory tract infections and to invite 4 individuals they had met in the preceding 2 weeks to take part in the study. We compared sociodemographic characteristics among panel participants, individuals who volunteered for our survey, and individuals recruited via respondent-driven detection. Results. Starting from 1015 panel members, the survey spread through all provinces of the Netherlands and all age groups in 83 days. A total of 433 individuals completed the survey via peer recruitment. Participants who reported symptoms were 6.1% (95% confidence interval = 5.4, 6.9) more likely to invite contact persons than were participants who did not report symptoms. Participants with symptoms invited more symptomatic recruits to take part than did participants without symptoms. Conclusions. Our findings suggest that online respondent-driven detection can enhance identification of symptomatic patients by making use of individuals’ local social networks.",,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G.\u2009M', 'Koppeschaar, Carl E.', 'Bengtsson, Linus', 'Thorson, Anna', 'Kretzschmar, Mirjam E.\u2009E']",,,,
,PMC,Disease risks associated with free-ranging wild boar in Saskatchewan,,PMC4502852,,,"This study investigated the disease status of Saskatchewan’s feral wild boar population. Whole carcasses, tissue samples, and/or serum from 81 hunter-killed boars from Saskatchewan were submitted to the Canadian Wildlife Health Cooperative (CWHC) between 2009 and 2014. Serological tests were negative for PRRS, H1N1, and H3N2 swine influenza, PCV-2, and TGE/PRCV in 22/22 boars and for Toxoplasma gondii and Mycoplasma hyopneumoniae in 20/20 boars. Of 20 boars whose sera were tested 20 were positive for Actinobacillus pleuropneumoniae, with 7 positive for, among other strains, serotype 14; 16 were positive for Lawsonia intracellularis, 1 was positive and 6 were suspicious for Salmonella spp. Polymerase chain reaction tests were negative for PRRS and PCV2 in 58/58 boars and positive for Torque teno virus in 1/8 boars. Digestion assays were negative for Trichinella spp. in 22/22 boars. The high seroprevalence of A. pleuropneumoniae serotype 14 is noteworthy as this serotype has not been previously reported in North America.",,"['McGregor, Glenna F.', 'Gottschalk, Marcelo', 'Godson, Dale L.', 'Wilkins, Wendy', 'Bollinger, Trent K.']",,,,
,PMC,The Function of TrophomiRs and Other MicroRNAs in the Human Placenta,http://dx.doi.org/10.1101/cshperspect.a023036,PMC4526727,,,"In eutherian organisms, the placenta interfaces the fetal and maternal environments. Located at the placental villous surface, in direct contact with maternal blood, is the trophoblast layer, which mediates the crucial maternal–fetal exchange of gases, nutrients, and waste products, produces hormones that support the pregnancy, and provides immunologic defense. Discovery of microRNAs (miRNAs) and their role in development, differentiation, and homeostatic resilience has increased our understanding of genomic and epigenomic networks that regulate placental function. Moreover, unique miRNA species, which are expressed by human trophoblasts and are termed “trophomiRs,” may show specialized functions during normal and pathological pregnancies. Placental miRNAs, packaged within exosomes and other vesicles or bound in protein complexes, are capable of communicating distinctive signals to maternal and/or fetal tissues. Additional research may usher in the use of circulating miRNAs as pregnancy-related disease biomarkers, providing new diagnostic and therapeutic options during pregnancy.",,"['Sadovsky, Yoel', 'Mouillet, Jean-Francois', 'Ouyang, Yingshi', 'Bayer, Avraham', 'Coyne, Carolyn B.']",,,,
,PMC,A Novel Loading Method for Doxycycline Liposomes for Intracellular Drug Delivery: Characterization of In Vitro and In Vivo Release Kinetics and Efficacy in a J774A.1 Cell Line Model of Mycobacterium smegmatis Infection,http://dx.doi.org/10.1124/dmd.115.063602,PMC4518064,,,"Doxycycline (doxy) is used in treating intracellular and extracellular infections. Liposomal (LE) antibiotics allow low-frequency dosing and extended efficacy compared with standard (STD) formulations. We developed a novel sulfuric acid–loading method for doxycycline liposomes (LE-doxy). We hypothesized that a single s.c. injection of LE-doxy would be detectable in serum for at least 2 weeks at concentrations equal to or better than STD-doxy and would be bactericidal in an in vitro Mycobacterium smegmatis infection of J774A.1 macrophage cells. Liposomes were encapsulated by sulfuric acid gradient loading, and release kinetics were performed in vitro and in vivo. LE-doxy made using 8.25 mg/ml doxycycline loaded for 24 hours achieved 97.77% capture in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 43.87% in sphingomyelin (sphing). Rats were injected s.c. with 50 mg/kg LE-doxy or 5 mg/kg STD-doxy, and serial blood samples were collected. Pharmacokinetics were analyzed using high-performance liquid chromatography. Liver and injection site skin samples were collected at euthanasia (4 weeks postinjection). Minimal histologic tissue reactions occurred after injection of STD (nonliposomal), DPPC, or sphing-doxy. DPPC-doxy had slightly faster in vitro leakage than sphing liposomes, although both were detectable at 264 hours. The mean residence time for DPPC was the highest (111.78 hours), followed by sphing (56.00 hours) and STD (6.86 hours). DPPC and sphing-doxy were detectable at 0.2 μg/ml in serum at 336 hours postadministration. LE-doxy was not toxic to J774A.1 cells in vitro and produced inhibition of viable Mycobacterium smegmatis at 24 and 48 hours. LE-doxy will require further testing in in vivo infection models.",,"['Franklin, Rebekah K.', 'Marcus, Sarah A.', 'Talaat, Adel M.', 'KuKanich, Butch K.', 'Sullivan, Ruth', 'Krugner-Higby, Lisa A.', 'Heath, Timothy D.']",,,,
,PMC,The Role of Scientific Collections in Scientific Preparedness,http://dx.doi.org/10.3201/eid2108.150423,PMC4517712,26380390,NO-CC CODE,"Building on the findings and recommendations of the Interagency Working Group on Scientific Collections, Scientific Collections International (SciColl) aims to improve the rapid access to science collections across disciplines within the federal government and globally, between government agencies and private research institutions. SciColl offered a novel opportunity for the US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, to explore the value of scientific research collections under the science preparedness initiative and integrate it as a research resource at each stage in the emergence of the infectious diseases cycle. Under the leadership of SciColl’s executive secretariat at the Smithsonian Institution, and with multiple federal and international partners, a workshop during October 2014 fully explored the intersections of the infectious disease cycle and the role scientific collections could play as an evidentiary scientific resource to mitigate risks associated with emerging infectious diseases.",2015 Aug,"DiEuliis, Diane",Emerg Infect Dis,,,
,PMC,The Weathervane,,PMC4536742,,,,,"Stodd, Russell T",,,,
,PMC,MERS may not be SARS; but India is still vulnerable,http://dx.doi.org/10.4103/0971-5916.164210,PMC4613429,26354205,CC BY-NC-SA,,2015 Aug,"Kant, Lalit",Indian J Med Res,,,
,PMC,Aerobic Bacteriological Study of Acute Exacerbations of Chronic Obstructive Pulmonary Disease,http://dx.doi.org/10.7860/JCDR/2015/14515.6367,PMC4576533,,,"BACKGROUND: The natural history of chronic obstructive pulmonary disease is characterized by frequent exacerbations. Majority of exacerbations are infectious and bacteria responsible for 30-50% of these cases. The purpose of this study was to determine the bacteriology of acute exacerbations of chronic obstructive pulmonary disease in hospitalized patients in our institution and their antibiotic susceptibility pattern to formulate cost effective antibiotic strategy and reducing the emergence of drug resistance. MATERIALS AND METHODS: One hundred and seven clinically diagnosed cases of acute exacerbations of chronic obstructive pulmonary disease admitted in medicine, tuberculosis and chest wards were selected for the study. Direct gram stain was done for all sputum samples. The suitable sputum samples were cultured. Identification of organism and antimicrobial susceptibility testing was done by standard microbiological techniques. RESULTS: Our study showed growth of pathogenic organisms in 41.12% cases. Males (67.29%) are more affected than females (32.71%). Gram negative bacilli were more isolated than gram positive cocci. The commonest isolate was Klebsiella pneumoniae 15 (38.46%), followed by Staphylococcus aureus 9 (23.08%), Streptococcus species 6 (15.39%), Pseudomonas aeruginosa 4 (10.26%), E.coli 2 (5.13%), Acinetobacter species 2 (5.13%) and Enterobacter species 1(2.56%). The antibiotic susceptibility reveals that vancomycin, linezolid, azithromycin and clarithromycin were most effective drugs for gram positive cocci, meropenem & piperacillin-tazobactam for gram negative bacilli and amikacin & levofloxacin for both gram positive cocci & gram negative bacilli. CONCLUSION: In developing country like India acute exacerbations of chronic obstructive pulmonary disease is common in adults more than 50 years of age due to smoking habits and high indoor pollution. This leads to a major impact on the quality of life of patients with the condition. They are a major cause of hospital admission and health care utilization.",,"Sharan, Hariom",,,,
,PMC,The use of next generation sequencing in the diagnosis and typing of respiratory infections,http://dx.doi.org/10.1016/j.jcv.2015.06.082,PMC4533236,26209388,CC BY,"BACKGROUND: Molecular assays are the gold standard methods used to diagnose viral respiratory pathogens. Pitfalls associated with this technique include limits to the number of targeted pathogens, the requirement for continuous monitoring to ensure sensitivity/specificity is maintained and the need to evolve to include emerging pathogens. Introducing target independent next generation sequencing (NGS) could resolve these issues and revolutionise respiratory viral diagnostics. OBJECTIVES: To compare the sensitivity and specificity of target independent NGS against the current standard diagnostic test. STUDY DESIGN: Diagnostic RT-PCR of clinical samples was carried out in parallel with target independent NGS. NGS sequences were analyzed to determine the proportion with viral origin and consensus sequences were used to establish viral genotypes and serotypes where applicable. RESULTS: 89 nasopharyngeal swabs were tested. A viral pathogen was detected in 43% of samples by NGS and 54% by RT-PCR. All NGS viral detections were confirmed by RT-PCR. CONCLUSIONS: Target independent NGS can detect viral pathogens in clinical samples. Where viruses were detected by RT-PCR alone the Ct value was higher than those detected by both assays, suggesting an NGS detection cut-off – Ct = 32. The sensitivity and specificity of NGS compared with RT-PCR was 78% and 80% respectively. This is lower than current diagnostic assays but NGS provided full genome sequences in some cases, allowing determination of viral subtype and serotype. Sequencing technology is improving rapidly and it is likely that within a short period of time sequencing depth will increase in-turn improving test sensitivity.",2015 Aug,"['Thorburn, Fiona', 'Bennett, Susan', 'Modha, Sejal', 'Murdoch, David', 'Gunson, Rory', 'Murcia, Pablo R.']",J Clin Virol,,,
,PMC,Discovery of a novel nidovirus in cattle with respiratory disease,http://dx.doi.org/10.1099/vir.0.000166,PMC4681066,,,"The family Coronaviridae represents a diverse group of vertebrate RNA viruses, all with genomes greater than 26 000 nt. Here, we report the discovery and genetic characterization of a novel virus present in cattle with respiratory disease. Phylogenetic characterization of this virus revealed that it clusters within the subfamily Torovirinae, in the family Coronaviridae. The complete genome consists of only 20 261 nt and represents the smallest reported coronavirus genome. We identified seven ORFs, including the canonical nidovirus ORF1a and ORF1b. Analysis of polyprotein 1ab revealed that this virus, tentatively named bovine nidovirus (BoNV), shares the highest homology with the recently described python-borne nidoviruses and contains several conserved nidovirus motifs, but does not encode the NendoU or O-MT domains that are present in other viruses within the family Coronaviridae. In concert with its reduced genome, the atypical domain architecture indicates that this virus represents a unique lineage within the order Nidovirales.",,"['Tokarz, Rafal', 'Sameroff, Stephen', 'Hesse, Richard A.', 'Hause, Ben M.', 'Desai, Aaloki', 'Jain, Komal', 'Ian Lipkin, W.']",,,,
,PMC,Antimicrobial photodynamic inactivation in nanomedicine: small light strides against bad bugs,http://dx.doi.org/10.2217/nnm.15.67,PMC4557875,,,"The relentless advance of drug-resistance among pathogenic microbes, mandates a search for alternative approaches that will not cause resistance. Photodynamic inactivation (PDI) involves the combination of nontoxic dyes with harmless visible light to produce reactive oxygen species that can selectively kill microbial cells. PDI can be broad-spectrum in nature and can also destroy microbial cells in biofilms. Many different kinds of nanoparticles have been studied to potentiate antimicrobial PDI by improving photosensitizer solubility, photochemistry, photophysics and targeting. This review will cover photocatalytic disinfection with titania nanoparticles, carbon nanomaterials (fullerenes, carbon nanotubes and graphene), liposomes and polymeric nanoparticles. Natural polymers (chitosan and cellulose), gold and silver plasmonic nanoparticles, mesoporous silica, magnetic and upconverting nanoparticles have all been used for PDI.",,"['Yin, Rui', 'Agrawal, Tanupriya', 'Khan, Usman', 'Gupta, Gaurav K', 'Rai, Vikrant', 'Huang, Ying-Ying', 'Hamblin, Michael R']",,,,
,PMC,On-Demand Formation of Supported Lipid Membrane Arrays by Trehalose-Assisted Vesicle Delivery for SPR Imaging,http://dx.doi.org/10.1021/acsami.5b03809,PMC5412510,,,"The fabrication of large-scale, solid-supported lipid bilayer (SLB) arrays has traditionally been an arduous and complex task, primarily due to the need to maintain SLBs within an aqueous environment. In this work, we demonstrate the use of trehalose vitrified phospholipid vesicles that facilitate on-demand generation of microarrays, allowing each element a unique composition, for the label-free and high-throughput analysis of biomolecular interactions by SPR imaging (SPRi). Small, unilamellar vesicles (SUVs) are suspended in trehalose, deposited in a spatially defined manner, with the trehalose vitrifying on either hydrophilic or hydrophobic SPR substrates. SLBs are subsequently spontaneously formed on-demand simply by in situ hydration of the array in the SPR instrument flow cell. The resulting SLBs exhibit high lateral mobility, characteristic of fluidic cellular lipid membranes, and preserve the biological function of embedded cell membrane receptors, as indicated by SPR affinity measurements. Independent fluorescence and SPR imaging studies show that the individual SLBs stay localized at the area of deposition, without any encapsulating matrix, confining coral, or boundaries. The introduced methodology allows individually addressable SLB arrays to be analyzed with excellent label-free sensitivity in a real-time, high-throughput manner. Various protein–ganglioside interactions have been selected as a model system to illustrate discrimination of strong and weak binding responses in SPRi sensorgrams. This methodology has been applied toward generating hybrid bilayer membranes on hydrophobic SPR substrates, demonstrating its versatility toward a range of surfaces and membrane geometries. The stability of the fabricated arrays, over medium to long storage periods, was evaluated and found to be good. The highly efficient and easily scalable nature of the method has the potential to be applied to a variety of label-free sensing platforms requiring lipid membranes for high-throughput analysis of their properties and constituents.",,"['Hinman, Samuel S.', 'Ruiz, Charles J.', 'Drakakaki, Georgia', 'Wilkop, Thomas E.', 'Cheng, Quan']",,,,
,PMC,Resistance to synthetic blood penetration of National Institute for Occupational Safety and Health-approved N95 filtering facepiece respirators and surgical N95 respirators,http://dx.doi.org/10.1016/j.ajic.2015.06.014,PMC4658509,,,"BACKGROUND: Surgical N95 filtering facepiece respirators (FFRs), certified by the National Institute for Occupational Safety and Health (NIOSH) as a respirator and cleared by the Food and Drug Administration (FDA) as a surgical mask, are often used to protect from the inhalation of infectious aerosols and from splashes/sprays of body fluids in health care facilities. A shortage of respirators can be expected during a pandemic. The availability of surgical N95 FFRs can potentially be increased by incorporating FDA clearance requirements in the NIOSH respirator approval process. METHODS: Fluid resistance of NIOSH-approved N95 FFRs, and FDA-cleared surgical N95 FFRs and surgical masks was tested using the ASTM F1862 method at 450 and 635 cm/sec velocities and compared with the results from a third-party independent laboratory. Blood penetration through different layers of filter media of masks were also analyzed visually. RESULTS: Four N95 FFR models showed no test failures at both velocities. The penetration results obtained in the NIOSH laboratory were comparable to those from the third-party independent laboratory. The number of respirator samples failing the test increased with increasing test velocity. CONCLUSIONS: The results indicate that several NIOSH-approved N95 FFR models would likely pass FD clearance requirements for resistance to synthetic blood penetration.",,"['Rengasamy, Samy', 'Sbarra, Deborah', 'Nwoko, Julian', 'Shaffer, Ronald']",,,,
,PMC,Clinical and Molecular Epidemiology of Human Rhinovirus Infections in Patients with Hematologic Malignancy,http://dx.doi.org/10.1016/j.jcv.2015.07.309,PMC4750469,,,"BACKGROUND: Human rhinoviruses (HRVs) are common causes of upper respiratory tract infection (URTI) in hematologic malignancy (HM) patients. Predictors of lower respiratory tract infection (LRTI) including the impact of HRV species and types are poorly understood. OBJECTIVES: This study aims to describe the clinical and molecular epidemiology of HRV infections among HM patients. STUDY DESIGN: From April 2012–March 2013, HRV-positive respiratory specimens from symptomatic HM patients were molecularly characterized by analysis of partial viral protein 1 (VP1) or VP4 gene sequence. HRV LRTI risk-factors and outcomes were analyzed using multivariable logistic regression. RESULTS: One hundred and ten HM patients presented with HRV URTI (n=78) and HRV LRTI (n=32). Hypoalbuminemia (OR 3.0; 95% CI, 1.0 – 9.2; p=0.05) was independently associated with LRTI, but other clinical and laboratory markers of host immunity did not differ between patients with URTI versus LRTI. Detection of bacterial co-pathogens was common in LRTI cases (25%). Among 92 typeable respiratory specimens, there were 58 (64%) HRV-As, 12 (13%) HRV-Bs, and 21 (23%) HRV-Cs, and one Enterovirus 68. LRTI rates among HRV-A (29%), HRV-B (17%), and HRV-C (29%) were similar. HRV-A infections occurred year-round while HRV-B and HRV-C infections clustered in the late fall and winter. CONCLUSIONS: HRVs are associated with LRTI in HM patients. Illness severity is not attributable to specific HRV species or types. The frequent detection of bacterial co-pathogens in HRV LRTIs further substantiates the hypothesis that HRVs predispose to bacterial superinfection of the lower airways, similar to that of other community-acquired respiratory viruses.",,"['Jacobs, Samantha E.', 'Lamson, Daryl M.', 'Soave, Rosemary', 'Guzman, Brigitte Huertas', 'Shore, Tsiporah B.', 'Ritchie, Ellen K.', 'Zappetti, Dana', 'Satlin, Michael J.', 'Leonard, John P.', 'van Besien, Koen', 'Schuetz, Audrey N.', 'Jenkins, Stephen G.', 'St George, Kirsten', 'Walsh, Thomas J.']",,,,
,PMC,RIG-I Mediates an Antiviral Response to Crimean-Congo Hemorrhagic Fever Virus,http://dx.doi.org/10.1128/JVI.01643-15,PMC4580164,,,"In the cytoplasm, the retinoic acid-inducible gene I (RIG-I) senses the RNA genomes of several RNA viruses. RIG-I binds to viral RNA, eliciting an antiviral response via the cellular adaptor MAVS. Crimean-Congo hemorrhagic fever virus (CCHFV), a negative-sense RNA virus with a 5′-monophosphorylated genome, is a highly pathogenic zoonotic agent with significant public health implications. We found that, during CCHFV infection, RIG-I mediated a type I interferon (IFN) response via MAVS. Interfering with RIG-I signaling reduced IFN production and IFN-stimulated gene expression and increased viral replication. Immunostimulatory RNA was isolated from CCHFV-infected cells and from virion preparations, and RIG-I coimmunoprecipitation of infected cell lysates isolated immunostimulatory CCHFV RNA. This report serves as the first description of a pattern recognition receptor for CCHFV and highlights a critical signaling pathway in the antiviral response to CCHFV. IMPORTANCE CCHFV is a tick-borne virus with a significant public health impact. In order for cells to respond to virus infection, they must recognize the virus as foreign and initiate antiviral signaling. To date, the receptors involved in immune recognition of CCHFV are not known. Here, we investigate and identify RIG-I as a receptor involved in initiating an antiviral response to CCHFV. This receptor initially was not expected to play a role in CCHFV recognition because of characteristics of the viral genome. These findings are important in understanding the antiviral response to CCHFV and support continued investigation into the spectrum of potential viruses recognized by RIG-I.",,"['Spengler, Jessica R.', 'Patel, Jenish R.', 'Chakrabarti, Ayan K.', 'Zivcec, Marko', 'García-Sastre, Adolfo', 'Spiropoulou, Christina F.', 'Bergeron, Éric']",,,,
,PMC,Advax Delta Inulin Adjuvant Overcomes Immune Immaturity In Neonatal Mice Thereby Allowing Single–Dose Influenza Vaccine Protection,http://dx.doi.org/10.1016/j.vaccine.2015.07.051,PMC4562881,,,"Neonates are at high risk for influenza morbidity and mortality due to immune immaturity and lack of priming by prior exposure. Inactivated influenza vaccines are ineffective in infants under six months and to provide protection in older children generally require two doses given a month apart. This leaves few options for rapid protection of infants, e.g. during an influenza pandemic. We investigated whether Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles could help overcome neonatal immune hypo-responsiveness and also whether it was possible to obtain single-dose influenza vaccine protection of babies against lethal infection. Inactivated influenza A/H1N1 vaccine (iH1N1) combined with Advax™ adjuvant administered as a single immunization to 7-day-old mouse pups significantly enhanced serum influenza-specific IgM, IgG1, IgG2a and IgG2b levels in association with a 3–4 fold increase in the frequency of splenic influenza-specific IgM and IgG antibody secreting cells versus pups immunized with iH1N1 alone. Pups immunized with Advax-adjuvanted iH1N1 had significantly higher influenza-stimulated splenocyte production of IFN-γ, IL-2, IL-4, and IL-10 and a 3–10 fold higher frequency of T cells IFN-γ secreting IL-2, IL-4 or IL-17 by ELISPOT. Immunisation with iH1N1+Advax adjuvant induced robust protection against influenza virus challenge 3 weeks post-immunization, whereas pups immunized with iH1N1 alone had no protection. Protection by Advax-adjuvanted iH1N1 was mediated by serum antibody and memory B cells rather than memory T cells as protection was lost in neonatal µMT mice that are B-cell deficient. Hence, Advax adjuvant overcame neonatal immune hypo-responsiveness and enabled single-dose protection of pups against otherwise lethal influenza infection, thereby supporting development of Advax™ as a neonatal vaccine adjuvant.",,"['Honda-Okubo, Yoshikazu', 'Ong, Chun Hao', 'Petrovsky, Nikolai']",,,,
,PMC,Crystallographic analysis of the N-terminal domain of Middle East respiratory syndrome coronavirus nucleocapsid protein,http://dx.doi.org/10.1107/S2053230X15010146,PMC4528927,,,"The N-terminal domain of the nucleocapsid protein from Middle East respiratory syndrome coronavirus (MERS-CoV NP-NTD) contains many positively charged residues and has been identified to be responsible for RNA binding during ribonucleocapsid formation by the virus. In this study, the crystallization and crystallographic analysis of MERS-CoV NP-NTD (amino acids 39–165), with a molecular weight of 14.7 kDa, are reported. MERS-CoV NP-NTD was crystallized at 293 K using PEG 3350 as a precipitant and a 94.5% complete native data set was collected from a cooled crystal at 77 K to 2.63 Å resolution with an overall R (merge) of 9.6%. The crystals were monoclinic and belonged to space group P2(1), with unit-cell parameters a = 35.60, b = 109.64, c = 91.99 Å, β = 101.22°. The asymmetric unit contained four MERS-CoV NP-NTD molecules.",,"['Wang, Yong-Sheng', 'Chang, Chung-ke', 'Hou, Ming-Hon']",,,,
,PMC,Management of severe viral infections in the pediatric intensive care unit,http://dx.doi.org/10.3233/PIC-14103,PMC6530759,,,"Viral infections are major causes of morbidity and mortality among children worldwide. All children, regardless of geographic region, socio-economic status, or age, are vulnerable to severe viral infections. They often require specialized care that ideally necessitates admission to an intensive care unit. This article will review the major viral syndromes and pathogens that affect children, focusing on the current evidence for their acute management in the intensive care unit.",,"['Murthy, Srinivas', 'Kissoon, Niranjan']",,,,
,PMC,Idiopathic pneumonia syndrome following hematopoietic stem cell transplantation,http://dx.doi.org/10.3233/PIC-14098,PMC6530755,,,"Non-infectious lung injury following hematopoietic stem cell transplant may be driven by either immune or non-immune pathways of inflammation. Common alloimmune lung complications include idiopathic pneumonia syndrome (IPS), transfusion related lung injury, diffuse alveolar hemorrhage, and peri-engraftment respiratory distress syndrome, with both diffuse alveolar hemorrhage and peri-engraftment respiratory distress syndrome existing as subsets of IPS when infection is absent. This review will discuss the definitions, risk factors, and pathogeneses of IPS and highlight the diagnostic work-up and novel approaches to treatment.",,"['Klein, Orly R.', 'Cooke, Kenneth R.']",,,,
,PMC,A review of pathogens causing lower respiratory tract infection in the pediatric hematopoietic stem cell transplant recipient,http://dx.doi.org/10.3233/PIC-14093,PMC6530749,,,"Pediatric hematopoietic stem cell transplant recipients are at risk for acquiring a variety of lower respiratory tract infections (LRTI), which result in frequent pediatric intensive care unit admission with high mortality. Recent advances in conditioning regimens, opportunistic infection prophylaxis, diagnostic tools, and treatment modalities have broadly impacted our understanding of LRTI among these vulnerable patients. In this review, the most common bacteria, viruses, and fungi causing LRTI in pediatric hematopoietic stem cell transplant patients are discussed.",,"['Zinter, Matt S.', 'Levy, Emily R.', 'Gertz, Shira J.']",,,,
,PMC,Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus,http://dx.doi.org/10.1073/pnas.1510199112,PMC4547275,,,"Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection caused by a previously unidentified coronavirus (CoV), likely transmitted to humans by infected camels. There is no licensed vaccine or antiviral for MERS, therefore new prophylactic and therapeutic strategies to combat human infections are needed. In this study, we describe, for the first time, to our knowledge, the isolation of a potent MERS-CoV–neutralizing antibody from memory B cells of an infected individual. The antibody, named LCA60, binds to a novel site on the spike protein and potently neutralizes infection of multiple MERS-CoV isolates by interfering with the binding to the cellular receptor CD26. Importantly, using mice transduced with adenovirus expressing human CD26 and infected with MERS-CoV, we show that LCA60 can effectively protect in both prophylactic and postexposure settings. This antibody can be used for prophylaxis, for postexposure prophylaxis of individuals at risk, or for the treatment of human cases of MERS-CoV infection. The fact that it took only 4 mo from the initial screening of B cells derived from a convalescent patient for the development of a stable chinese hamster ovary (CHO) cell line producing neutralizing antibodies at more than 5 g/L provides an example of a rapid pathway toward the generation of effective antiviral therapies against emerging viruses.",,"['Corti, Davide', 'Zhao, Jincun', 'Pedotti, Mattia', 'Simonelli, Luca', 'Agnihothram, Sudhakar', 'Fett, Craig', 'Fernandez-Rodriguez, Blanca', 'Foglierini, Mathilde', 'Agatic, Gloria', 'Vanzetta, Fabrizia', 'Gopal, Robin', 'Langrish, Christopher J.', 'Barrett, Nicholas A', 'Sallusto, Federica', 'Baric, Ralph S.', 'Varani, Luca', 'Zambon, Maria', 'Perlman, Stanley', 'Lanzavecchia, Antonio']",,,,
,PMC,Editorial overview: Progress and challenges in modeling human viral diseases in vivo,http://dx.doi.org/10.1016/j.coviro.2015.07.004,PMC6040652,,,,,"['Ploss, Alexander', 'Walker, Christopher']",,,,
,PMC,Viral nucleases induce an mRNA degradation-transcription feedback loop in mammalian cells,http://dx.doi.org/10.1016/j.chom.2015.06.019,PMC4538998,,,"Gamma-herpesviruses encode a cytoplasmic mRNA-targeting endonuclease, SOX, that cleaves most cellular mRNAs. Cleaved fragments are subsequently degraded by the cellular 5′-3′ mRNA exonuclease Xrn1, thereby suppressing cellular gene expression and facilitating viral evasion of host defenses. We reveal that mammalian cells respond to this widespread cytoplasmic mRNA decay by altering RNA polymerase II (RNAPII) transcription in the nucleus. Measuring RNAPII recruitment to promoters and nascent mRNA synthesis revealed that the majority of affected genes are transcriptionally repressed in SOX-expressing cells. The transcriptional feedback does not occur in response to the initial viral endonuclease-induced cleavage, but instead to degradation of the cleaved fragments by cellular exonucleases. In particular, Xrn1 catalytic activity is required for transcriptional repression. Notably, viral mRNA transcription escapes decay-induced repression, and this escape requires Xrn1. Collectively, these results indicate that mRNA decay rates impact transcription, and that gamma-herpesviruses use this feedback mechanism to facilitate viral gene expression.",,"['Abernathy, Emma', 'Gilbertson, Sarah', 'Alla, Ravi', 'Glaunsinger, Britt']",,,,
,PMC,Quantitative proteomics identifies serum response factor binding protein 1 as a host factor for hepatitis C virus entry,http://dx.doi.org/10.1016/j.celrep.2015.06.063,PMC4836839,,,"Hepatitis C virus (HCV) enters human hepatocytes through a multistep mechanism involving, among other host proteins, the virus receptor CD81. How CD81 governs HCV entry is poorly characterized and CD81 protein interactions after virus binding remain elusive. We have developed a quantitative proteomics protocol to identify HCV-triggered CD81 interactions and found 26 dynamic binding partners. At least six of these proteins promote HCV infection as indicated by RNA interference. We further characterized serum response factor binding protein 1 (SRFBP1), which is recruited to CD81 during HCV uptake and supports HCV infection in hepatoma cells and primary human hepatocytes. SRFBP1 facilitates host cell penetration by all seven HCV genotypes, but not of vesicular stomatitis virus and human coronavirus. Thus, SRFBP1 is an HCV specific, pan-genotypic host entry factor. These results demonstrate the use of quantitative proteomics to elucidate pathogen entry and underscore the importance of host protein-protein interactions during HCV invasion.",,"['Gerold, Gisa', 'Meissner, Felix', 'Bruening, Janina', 'Welsch, Kathrin', 'Perin, Paula M.', 'Baumert, Thomas F.', 'Vondran, Florian W.', 'Kaderali, Lars', 'Marcotrigiano, Joseph', 'Khan, Abdul G.', 'Mann, Matthias', 'Rice, Charles M.', 'Pietschmann, Thomas']",,,,
,PMC,Discovery of T-Cell Infection and Apoptosis by Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1093/infdis/jiv381,PMC4760413,,,,,"['Ying, Tianlei', 'Li, Wei', 'Dimitrov, Dimiter S.']",,,,
,PMC,Brain Invasion by Mouse Hepatitis Virus Depends on Impairment of Tight Junctions and Beta Interferon Production in Brain Microvascular Endothelial Cells,http://dx.doi.org/10.1128/JVI.01501-15,PMC4577898,,,"Coronaviruses (CoVs) have shown neuroinvasive properties in humans and animals secondary to replication in peripheral organs, but the mechanism of neuroinvasion is unknown. The major aim of our work was to evaluate the ability of CoVs to enter the central nervous system (CNS) through the blood-brain barrier (BBB). Using the highly hepatotropic mouse hepatitis virus type 3 (MHV3), its attenuated variant, 51.6-MHV3, which shows low tropism for endothelial cells, and the weakly hepatotropic MHV-A59 strain from the murine coronavirus group, we investigated the virus-induced dysfunctions of BBB in vivo and in brain microvascular endothelial cells (BMECs) in vitro. We report here a MHV strain-specific ability to cross the BBB during acute infection according to their virulence for liver. Brain invasion was observed only in MHV3-infected mice and correlated with enhanced BBB permeability associated with decreased expression of zona occludens protein 1 (ZO-1), VE-cadherin, and occludin, but not claudin-5, in the brain or in cultured BMECs. BBB breakdown in MHV3 infection was not related to production of barrier-dysregulating inflammatory cytokines or chemokines by infected BMECs but rather to a downregulation of barrier protective beta interferon (IFN-β) production. Our findings highlight the importance of IFN-β production by infected BMECs in preserving BBB function and preventing access of blood-borne infectious viruses to the brain. IMPORTANCE Coronaviruses (CoVs) infect several mammals, including humans, and are associated with respiratory, gastrointestinal, and/or neurological diseases. There is some evidence that suggest that human respiratory CoVs may show neuroinvasive properties. Indeed, the severe acute respiratory syndrome coronavirus (SARS-CoV), causing severe acute respiratory syndrome, and the CoVs OC43 and 229E were found in the brains of SARS patients and multiple sclerosis patients, respectively. These findings suggest that hematogenously spread CoVs may gain access to the CNS at the BBB level. Herein we report for the first time that CoVs exhibit the ability to cross the BBB according to strain virulence. BBB invasion by CoVs correlates with virus-induced disruption of tight junctions on BMECs, leading to BBB dysfunction and enhanced permeability. We provide evidence that production of IFN-β by BMECs during CoV infection may prevent BBB breakdown and brain viral invasion.",,"['Bleau, Christian', 'Filliol, Aveline', 'Samson, Michel', 'Lamontagne, Lucie']",,,,
,PMC,"Sex matters – a preliminary analysis of Middle East respiratory syndrome in the Republic of Korea, 2015",http://dx.doi.org/10.5365/WPSAR.2015.6.3.002,PMC4675154,,,,,"['Jansen, Andreas', 'Chiew, May', 'Konings, Frank', 'Lee, Chin-Kei', 'Ailan, Li', None, None]",,,,
,PMC,Interferon-λ: immune functions at barrier surfaces and beyond,http://dx.doi.org/10.1016/j.immuni.2015.07.001,PMC4527169,,,"When type III interferon (IFN-λ; also known as interleukin-28 (IL-28) and IL-29) was discovered in 2003, its antiviral function was expected to be analogous to the type I IFNs (IFN-α and IFN-β), via the induction of IFN-stimulated genes (ISGs). While IFN-λ stimulates expression of antiviral ISGs preferentially in cells of epithelial origin, recent studies have defined additional antiviral mechanisms in other cell types and tissues. Models of viral infection using mice lacking IFN-λ signaling and single nucleotide polymorphism (SNP) associations with human disease have expanded our understanding of the contribution of IFN-λ to the antiviral response at anatomic barriers and the immune response beyond these barriers. In this review, we highlight recent insights into the functions of IFN-λ, including its ability to restrict virus spread into the brain and to clear chronic viral infections in the gastrointestinal tract. We also discuss how IFN-λ modulates innate and adaptive immunity, autoimmunity, and tumor progression and its possible therapeutic applications in human disease.",,"['Lazear, Helen M.', 'Nice, Timothy J.', 'Diamond, Michael S.']",,,,
,PMC,The cytokine storm of severe influenza and development of immunomodulatory therapy,http://dx.doi.org/10.1038/cmi.2015.74,PMC4711683,,,"Severe influenza remains unusual in its virulence for humans. Complications or ultimately death arising from these infections are often associated with hyperinduction of proinflammatory cytokine production, which is also known as ‘cytokine storm'. For this disease, it has been proposed that immunomodulatory therapy may improve the outcome, with or without the combination of antiviral agents. Here, we review the current literature on how various effectors of the immune system initiate the cytokine storm and exacerbate pathological damage in hosts. We also review some of the current immunomodulatory strategies for the treatment of cytokine storms in severe influenza, including corticosteroids, peroxisome proliferator-activated receptor agonists, sphingosine-1-phosphate receptor 1 agonists, cyclooxygenase-2 inhibitors, antioxidants, anti-tumour-necrosis factor therapy, intravenous immunoglobulin therapy, statins, arbidol, herbs, and other potential therapeutic strategies.",,"['Liu, Qiang', 'Zhou, Yuan-hong', 'Yang, Zhan-qiu']",,,,
,PMC,Development and Evaluation of Novel Real-Time Reverse Transcription-PCR Assays with Locked Nucleic Acid Probes Targeting Leader Sequences of Human-Pathogenic Coronaviruses,http://dx.doi.org/10.1128/JCM.01224-15,PMC4508434,,,"Based on findings in small RNA-sequencing (Seq) data analysis, we developed highly sensitive and specific real-time reverse transcription (RT)-PCR assays with locked nucleic acid probes targeting the abundantly expressed leader sequences of Middle East respiratory syndrome coronavirus (MERS-CoV) and other human coronaviruses. Analytical and clinical evaluations showed their noninferiority to a commercial multiplex PCR test for the detection of these coronaviruses.",,"['Chan, Jasper Fuk-Woo', 'Choi, Garnet Kwan-Yue', 'Tsang, Alan Ka-Lun', 'Tee, Kah-Meng', 'Lam, Ho-Yin', 'Yip, Cyril Chik-Yan', 'To, Kelvin Kai-Wang', 'Cheng, Vincent Chi-Chung', 'Yeung, Man-Lung', 'Lau, Susanna Kar-Pui', 'Woo, Patrick Chiu-Yat', 'Chan, Kwok-Hung', 'Tang, Bone Siu-Fai', 'Yuen, Kwok-Yung']",,,,
,PMC,Application of Multiplex PCR Coupled with Matrix-Assisted Laser Desorption Ionization–Time of Flight Analysis for Simultaneous Detection of 21 Common Respiratory Viruses,http://dx.doi.org/10.1128/JCM.00943-15,PMC4508422,,,"Respiratory infections continue to pose a significant threat to human health. It is important to accurately and rapidly detect respiratory viruses. To compensate for the limits of current respiratory virus detection methods, we developed a 24-plex analysis (common respiratory virus-mass spectrometry [CRV-MS]) that can simultaneously detect and identify 21 common respiratory viruses based on a matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry system. To evaluate the efficacy of the CRV-MS method, we used 102 samples that were confirmed positive for these common respiratory viruses. All tests using the CRV-MS method were effective, with no cross-reactivity observed with other common respiratory viruses. To confirm the usefulness of the CRV-MS method, we screened 336 nasal and throat swabs that were collected from adults or children with suspected viral acute respiratory tract infections using the CRV-MS method and consensus PCR/reverse transcription-PCR (RT-PCR) methods. Excluding four RNase P-negative samples, the CRV-MS and consensus PCR/RT-PCR methods detected respiratory viruses in 92.5% (307/332) and 89.5% (297/332) of the samples, respectively. The two methods yielded identical results for 306 (92.2%) samples, including negative results for 25 samples (7.5%) and positive results for 281 samples (84.6%). Differences between the two methods may reflect their different sensitivities. The CRV-MS method proved to be sensitive and robust, and it can be used in large-scale epidemiological studies of common respiratory virus infections.",,"['Zhang, Chi', 'Xiao, Yan', 'Du, Jiang', 'Ren, Lili', 'Wang, Jianwei', 'Peng, Junping', 'Jin, Qi']",,,,
,PMC,Global trends in infectious diseases at the wildlife–livestock interface,http://dx.doi.org/10.1073/pnas.1422741112,PMC4534210,,,"The role and significance of wildlife–livestock interfaces in disease ecology has largely been neglected, despite recent interest in animals as origins of emerging diseases in humans. Scoping review methods were applied to objectively assess the relative interest by the scientific community in infectious diseases at interfaces between wildlife and livestock, to characterize animal species and regions involved, as well as to identify trends over time. An extensive literature search combining wildlife, livestock, disease, and geographical search terms yielded 78,861 publications, of which 15,998 were included in the analysis. Publications dated from 1912 to 2013 and showed a continuous increasing trend, including a shift from parasitic to viral diseases over time. In particular there was a significant increase in publications on the artiodactyls–cattle and bird–poultry interface after 2002 and 2003, respectively. These trends could be traced to key disease events that stimulated public interest and research funding. Among the top 10 diseases identified by this review, the majority were zoonoses. Prominent wildlife–livestock interfaces resulted largely from interaction between phylogenetically closely related and/or sympatric species. The bird–poultry interface was the most frequently cited wildlife–livestock interface worldwide with other interfaces reflecting regional circumstances. This review provides the most comprehensive overview of research on infectious diseases at the wildlife–livestock interface to date.",,"['Wiethoelter, Anke K.', 'Beltrán-Alcrudo, Daniel', 'Kock, Richard', 'Mor, Siobhan M.']",,,,
,PMC,Clonality and intracellular polyploidy in virus evolution and pathogenesis,http://dx.doi.org/10.1073/pnas.1501715112,PMC4517279,,,"In the present article we examine clonality in virus evolution. Most viruses retain an active recombination machinery as a potential means to initiate new levels of genetic exploration that go beyond those attainable solely by point mutations. However, despite abundant recombination that may be linked to molecular events essential for genome replication, herein we provide evidence that generation of recombinants with altered biological properties is not essential for the completion of the replication cycles of viruses, and that viral lineages (near-clades) can be defined. We distinguish mechanistically active but inconsequential recombination from evolutionarily relevant recombination, illustrated by episodes in the field and during experimental evolution. In the field, recombination has been at the origin of new viral pathogens, and has conferred fitness advantages to some viruses once the parental viruses have attained a sufficient degree of diversification by point mutations. In the laboratory, recombination mediated a salient genome segmentation of foot-and-mouth disease virus, an important animal pathogen whose genome in nature has always been characterized as unsegmented. We propose a model of continuous mutation and recombination, with punctuated, biologically relevant recombination events for the survival of viruses, both as disease agents and as promoters of cellular evolution. Thus, clonality is the standard evolutionary mode for viruses because recombination is largely inconsequential, since the decisive events for virus replication and survival are not dependent on the exchange of genetic material and formation of recombinant (mosaic) genomes.",,"['Perales, Celia', 'Moreno, Elena', 'Domingo, Esteban']",,,,
,PMC,Hospitalization Fatality Risk of Influenza A(H1N1)pdm09: A Systematic Review and Meta-Analysis,http://dx.doi.org/10.1093/aje/kwv054,PMC4528954,,,"During the 2009 influenza pandemic, uncertainty surrounding the severity of human infections with the influenza A(H1N1)pdm09 virus hindered the calibration of the early public health response. The case fatality risk was widely used to assess severity, but another underexplored and potentially more immediate measure is the hospitalization fatality risk (HFR), defined as the probability of death among H1N1pdm09 cases who required hospitalization for medical reasons. In this review, we searched for relevant studies published in MEDLINE (PubMed) and EMBASE between April 1, 2009, and January 9, 2014. Crude estimates of the HFR ranged from 0% to 52%, with higher estimates from tertiary-care referral hospitals in countries with a lower gross domestic product, but in wealthy countries the estimate was 1%–3% in all settings. Point estimates increased substantially with age and with lower gross domestic product. Early in the next pandemic, estimation of a standardized HFR may provide a picture of the severity of infection, particularly if it is presented in comparison with a similarly standardized HFR for seasonal influenza in the same setting.",,"['Wong, Jessica Y.', 'Kelly, Heath', 'Cheung, Chung-Mei M.', 'Shiu, Eunice Y.', 'Wu, Peng', 'Ni, Michael Y.', 'Ip, Dennis K. M.', 'Cowling, Benjamin J.']",,,,
,PMC,Animal models of Middle East Respiratory Syndrome coronavirus infection,http://dx.doi.org/10.1016/j.antiviral.2015.07.005,PMC4561025,,,"The emergence of the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second time that a new, highly pathogenic coronavirus has emerged in the human population in the 21(st) century. In this review, we discuss the current state of knowledge of animal models of MERS-CoV infection. Commonly used laboratory animal species such as Syrian hamsters, mice and ferrets are not susceptible to MERS-CoV, due to differences in the MERS-CoV receptor dipeptyl peptidase 4 (DPP4). The initially developed animal models comprise two nonhuman primate species, the rhesus macaque and the common marmoset. Rhesus macaques develop a mild to moderate respiratory disease upon inoculation, reminiscent of milder MERS cases, whereas marmosets develop a moderate to severe respiratory disease, recapitulating the severe disease observed in some patients. Dromedary camels, considered to be the reservoir for MERS-CoV, develop a mild upper respiratory tract infection with abundant viral shedding. Although normal mice are not susceptible to MERS-CoV, expression of the human DPP4 (hDPP4) overcomes the lack of susceptibility. Transgenic hDPP4 mice develop severe and lethal respiratory disease upon inoculation with MERS-CoV. These hDPP4 transgenic mice are potentially the ideal first line animal model for efficacy testing of therapeutic and prophylactic countermeasures. Further characterization of identified countermeasures would ideally be performed in the common marmoset model, due to the more severe disease outcome. This article forms part of a symposium in Antiviral Research on “From SARS to MERS: research on highly pathogenic human coronaviruses.”",,"['van Doremalen, Neeltje', 'Munster, Vincent J.']",,,,
,PMC,Inactivation and safety testing of Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1016/j.jviromet.2015.07.002,PMC4555185,,,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a recently emerged virus that has caused a number of human infections and deaths, primarily in the Middle East. The transmission of MERS-CoV to humans has been proposed to be as a result of contact with camels, but evidence of human-to-human transmission also exists. In order to work with MERS-CoV in a laboratory setting, the US Centers for Disease Control and Prevention (CDC) has determined that MERS-CoV should be handled at a biosafety level (BSL) 3 (BSL-3) biocontainment level. Many processes and procedures used to characterize MERS-CoV and to evaluate samples from MERS-CoV infected animals are more easily and efficiently completed at BSL-2 or lower containment. In order to complete experimental work at BSL-2, demonstration or proof of inactivation is required before removal of specimens from biocontainment laboratories. In the studies presented here, we evaluated typical means of inactivating viruses prior to handling specimens at a lower biocontainment level. We found that Trizol, AVL buffer and gamma irradiation were effective at inactivating MERS-CoV, that formaldehyde-based solutions required at least 30 minutes of contact time in a cell culture system while a mixture of methanol and acetone required 60 minutes to inactivate MERS-CoV. Together, these data provide a foundation for safely inactivating MERS-CoV, and potentially other coronaviruses, prior to removal from biocontainment facilities.",,"['Kumar, Mia', 'Mazur, Steven', 'Ork, Britini L.', 'Postnikova, Elena', 'Hensley, Lisa E.', 'Jahrling, Peter B.', 'Johnson, Reed', 'Holbrook, Michael R.']",,,,
,PMC,Structure–Activity Relationship Studies of Substituted 2-(Isoxazol-3-yl)-2-oxo-N′-phenyl-acetohydrazonoyl Cyanide Analogues: Identification of Potent Exchange Proteins Directly Activated by cAMP (EPAC) Antagonists,http://dx.doi.org/10.1021/acs.jmedchem.5b00635,PMC4769034,,,"Exchange proteins directly activated by cAMP (EPAC) as guanine nucleotide exchange factors mediate the effects of the pivotal second messenger cAMP, thereby regulating a wide variety of intracellular physiological and pathophysiological processes. A series of novel 2-(isoxazol-3-yl)-2-oxo-N′-phenyl-acetohydrazonoyl cyanide EPAC antagonists was synthesized and evaluated in an effort to optimize properties of the previously identified high-throughput (HTS) hit 1 (ESI-09). Structure–activity relationship (SAR) analysis led to the discovery of several more active EPAC antagonists (e.g., 22 (HJC0726), 35 (NY0123), and 47 (NY0173)) with low micromolar inhibitory activity. These inhibitors may serve as valuable pharmacological probes to facilitate our efforts in elucidating the biological functions of EPAC and developing potential novel therapeutics against human diseases. Our SAR results have also revealed that further modification at the 3-, 4-, and 5-positions of the phenyl ring as well as the 5-position of the isoxazole moiety may allow for the development of more potent EPAC antagonists.",,"['Ye, Na', 'Zhu, Yingmin', 'Chen, Haijun', 'Liu, Zhiqing', 'Mei, Fang C.', 'Wild, Christopher', 'Chen, Haiying', 'Cheng, Xiaodong', 'Zhou, Jia']",,,,
,PMC,Prevention of pneumococcal infections during mass gathering,http://dx.doi.org/10.1080/21645515.2015.1058456,PMC5049738,,,"The interest in mass gathering and its implications has been increasing due to globalization and international travel. The potential occurrence of infectious disease outbreaks during mass gathering is most feared. In this context, respiratory tract infections are of great concern due to crowding in a limited space which facilitates and magnifies the potential of disease spread among attendees. Pneumococcal disease is best described among pilgrims to Makkah and vaccination is one of the methods for the prevention of this disease. Pneumonia was described in a mass gathering with a prevalence of 4.8/100,000 pilgrims and contributes to 15–39% of hospitalizations. Various studies showed that 7–37% of pilgrims are 65 y of age or older. The uptake of pneumococcal vaccine among pilgrims is low at 5%. There is no available data to make strong recommendations for S. pneumoniae vaccination of all pilgrims, it is important that a high risk population receive the indicated vaccination. We reviewed the available literature on the burden of pneumococcal infections during mass gathering and evaluate the available literature on pneumococcal vaccinations for attendees of mass gathering.",,"['Al-Tawfiq, Jaffar A', 'Memish, Ziad A']",,,,
,PMC,Remission of systemic lupus erythematosus disease activity with regulatory cytokine interleukin (IL)-35 in Murphy Roths Large (MRL)/lpr mice,http://dx.doi.org/10.1111/cei.12639,PMC4516441,,,"The immunological mechanisms mediated by regulatory cytokine interleukin (IL)-35 are unclear in systemic lupus erythematosus (SLE). We investigated the frequency of CD4(+)CD25(+)forkhead box protein 3 (FoxP3)(+) regulatory T (T(reg)) and IL-10(+) regulatory B (B(reg)) cells and related immunoregulatory mechanisms in a female Murphy Roths Large (MRL)/lpr mouse model of spontaneous lupus-like disease, with or without IL-35 treatment. A remission of histopathology characteristics of lupus flare and nephritis was observed in the MRL/lpr mice upon IL-35 treatment. Accordingly, IL-35 and IL-35 receptor subunits (gp130 and IL-12Rβ2) and cytokines of MRL/lpr and BALB/c mice (normal controls) were measured. The increased anti-inflammatory cytokines and decreased proinflammatory cytokines were possibly associated with the restoration of T(reg) and B(reg) frequency in MRL/lpr mice with IL-35 treatment, compared to phosphate-buffered saline (PBS) treatment. mRNA expressions of T(reg)-related FoxP3, IL-35 subunit (p35 and EBI3) and soluble IL-35 receptor subunit (gp130 and IL12Rβ2) in splenic cells were up-regulated significantly in IL-35-treated mice. Compared with the PBS treatment group, IL-35-treated MRL/lpr mice showed an up-regulation of T(reg)-related genes and the activation of IL-35-related intracellular Janus kinase/signal transducer and activator of transcription signal pathways, thereby indicating the immunoregulatory role of IL-35 in SLE. These in vivo findings may provide a biochemical basis for further investigation of the regulatory mechanisms of IL-35 for the treatment of autoimmune-mediated inflammation.",,"['Cai, Z', 'Wong, C K', 'Dong, J', 'Chu, M', 'Jiao, D', 'Kam, N W', 'Lam, C W K', 'Tam, L S']",,,,
,PMC,Animal models for SARS and MERS coronaviruses,http://dx.doi.org/10.1016/j.coviro.2015.06.009,PMC4550498,,,"The emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV), two strains of animal coronaviruses that crossed the species barrier to infect and cause severe respiratory infections in humans within the last 12 years, have taught us that coronaviruses represent a global threat that does not recognize international borders. We can expect to see other novel coronaviruses emerge in the future. An ideal animal model should reflect the clinical signs, viral replication and pathology seen in humans. In this review, we present factors to consider in establishing an animal model for the study of novel coronaviruses and compare the different animal models that have been employed to study SARS-CoV and MERS-CoV.",,"['Gretebeck, Lisa M', 'Subbarao, Kanta']",,,,
,PMC,Respiratory Viral Detection in Children and Adults: Comparing Asymptomatic Controls and Patients With Community-Acquired Pneumonia,http://dx.doi.org/10.1093/infdis/jiv323,PMC4721902,,,"Background. The clinical significance of viruses detected in patients with community-acquired pneumonia (CAP) is often unclear. Methods. We conducted a prospective study to identify the prevalence of 13 viruses in the upper respiratory tract of patients with CAP and concurrently enrolled asymptomatic controls with real-time reverse-transcriptase polymerase chain reaction. We compared age-stratified prevalence of each virus between patients with CAP and controls and used multivariable logistic regression to calculate attributable fractions (AFs). Results. We enrolled 1024 patients with CAP and 759 controls. Detections of influenza, respiratory syncytial virus, and human metapneumovirus were substantially more common in patients with CAP of all ages than in controls (AFs near 1.0). Parainfluenza and coronaviruses were also more common among patients with CAP (AF, 0.5–0.75). Rhinovirus was associated with CAP among adults (AF, 0.93) but not children (AF, 0.02). Adenovirus was associated with CAP only among children <2 years old (AF, 0.77). Conclusions. The probability that a virus detected with real-time reverse-transcriptase polymerase chain reaction in patients with CAP contributed to symptomatic disease varied by age group and specific virus. Detections of influenza, respiratory syncytial virus, and human metapneumovirus among patients with CAP of all ages probably indicate an etiologic role, whereas detections of parainfluenza, coronaviruses, rhinovirus, and adenovirus, especially in children, require further scrutiny.",,"['Self, Wesley H.', 'Williams, Derek J.', 'Zhu, Yuwei', 'Ampofo, Krow', 'Pavia, Andrew T.', 'Chappell, James D.', 'Hymas, Weston C.', 'Stockmann, Chris', 'Bramley, Anna M.', 'Schneider, Eileen', 'Erdman, Dean', 'Finelli, Lyn', 'Jain, Seema', 'Edwards, Kathryn M.', 'Grijalva, Carlos G.']",,,,
,PMC,Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults,http://dx.doi.org/10.1056/NEJMoa1500245,PMC4728150,,,"BACKGROUND: Community-acquired pneumonia is a leading infectious cause of hospitalization and death among U.S. adults. Incidence estimates of pneumonia confirmed radio-graphically and with the use of current laboratory diagnostic tests are needed. METHODS: We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among adults 18 years of age or older in five hospitals in Chicago and Nashville. Patients with recent hospitalization or severe immunosuppression were excluded. Blood, urine, and respiratory specimens were systematically collected for culture, serologic testing, antigen detection, and molecular diagnostic testing. Study radiologists independently reviewed chest radiographs. We calculated population-based incidence rates of community-acquired pneumonia requiring hospitalization according to age and pathogen. RESULTS: From January 2010 through June 2012, we enrolled 2488 of 3634 eligible adults (68%). Among 2320 adults with radiographic evidence of pneumonia (93%), the median age of the patients was 57 years (interquartile range, 46 to 71); 498 patients (21%) required intensive care, and 52 (2%) died. Among 2259 patients who had radio-graphic evidence of pneumonia and specimens available for both bacterial and viral testing, a pathogen was detected in 853 (38%): one or more viruses in 530 (23%), bacteria in 247 (11%), bacterial and viral pathogens in 59 (3%), and a fungal or mycobacterial pathogen in 17 (1%). The most common pathogens were human rhinovirus (in 9% of patients), influenza virus (in 6%), and Streptococcus pneumoniae (in 5%). The annual incidence of pneumonia was 24.8 cases (95% confidence interval, 23.5 to 26.1) per 10,000 adults, with the highest rates among adults 65 to 79 years of age (63.0 cases per 10,000 adults) and those 80 years of age or older (164.3 cases per 10,000 adults). For each pathogen, the incidence increased with age. CONCLUSIONS: The incidence of community-acquired pneumonia requiring hospitalization was highest among the oldest adults. Despite current diagnostic tests, no pathogen was detected in the majority of patients. Respiratory viruses were detected more frequently than bacteria. (Funded by the Influenza Division of the National Center for Immunizations and Respiratory Diseases.)",,"['Jain, S.', 'Self, W.H.', 'Wunderink, R.G.', 'Fakhran, S.', 'Balk, R.', 'Bramley, A.M.', 'Reed, C.', 'Grijalva, C.G.', 'Anderson, E.J.', 'Courtney, D.M.', 'Chappell, J.D.', 'Qi, C.', 'Hart, E.M.', 'Carroll, F.', 'Trabue, C.', 'Donnelly, H.K.', 'Williams, D.J.', 'Zhu, Y.', 'Arnold, S.R.', 'Ampofo, K.', 'Waterer, G.W.', 'Levine, M.', 'Lindstrom, S.', 'Winchell, J.M.', 'Katz, J.M.', 'Erdman, D.', 'Schneider, E.', 'Hicks, L.A.', 'McCullers, J.A.', 'Pavia, A.T.', 'Edwards, K.M.', 'Finelli, L.']",,,,
,PMC,In This Issue,http://dx.doi.org/10.1073/iti2815112,PMC4507223,,,,,,,,,
,PMC,Conjugation of toll-like receptor-7 agonist to gastric cancer antigen MG7-Ag exerts antitumor effects,http://dx.doi.org/10.3748/wjg.v21.i26.8052,PMC4499347,,,"AIM: To investigate the effects of our tumor vaccines on reversing immune tolerance and generating therapeutic response. METHODS: Vaccines were synthesized by solid phase using an Fmoc strategy, where a small molecule toll-like receptor-7 agonist (T7) was conjugated to a monoclonal gastric cancer 7 antigen mono-epitope (T7-MG1) or tri-epitope (T7-MG3). Cytokines were measured in both mouse bone marrow dendritic cells and mouse spleen lymphocytes after exposed to the vaccines. BALB/c mice were intraperitoneally immunized with the vaccines every 2 wk for a total of three times, and then subcutaneously challenged with Ehrlich ascites carcinoma (EAC) cells. Three weeks later, the mice were killed, and the tumors were surgically removed and weighed. Serum samples were collected from the mice, and antibody titers were determined by ELISA using an alkaline phosphate-conjugated detection antibody for total IgG. Antibody-dependent cell-mediated cytotoxicity was detected by the lactate dehydrogenase method using natural killer cells as effectors and antibody-labeled EAC cells as targets. Cytotoxic T lymphocyte activities were also detected by the lactate dehydrogenase method using lymphocytes as effectors and EAC cells as targets. RESULTS: Vaccines were successfully synthesized and validated by analytical high performance liquid chromatography and electrospray mass spectrometry, including T7, T7-MG1, and T7-MG3. Rapid inductions of tumor necrosis factor-α and interleukin-12 in bone marrow dendritic cells and interferon γ and interleukin-12 in lymphocytes occurred in vitro after T7, T7-MG1, and T7-MG3 treatment. Immunization with T7-MG3 reduced the EAC tumor burden in BALB/c mice to 62.64% ± 5.55% compared with PBS control (P < 0.01). Six or nine weeks after the first immunization, the monoclonal gastric cancer 7 antigen antibody increased significantly in the T7-MG3 group compared with the PBS control (P < 0.01). As for antibody-dependent cell-mediated cytotoxicity, antisera obtained by immunization with T7-MG3 were able to markedly enhance cell lysis compared to PBS control (31.58% ± 2.94% vs 18.02% ± 2.26%; P < 0.01). As for cytotoxic T lymphocytes, T7-MG3 exhibited obviously greater cytotoxicity compared with PBS control (40.92% ± 4.38% vs 16.29% ± 1.90%; P < 0.01). CONCLUSION: A successful method is confirmed for the design of gastric cancer vaccines by chemical conjugation of T7 and multi-repeat-epitope of monoclonal gastric cancer 7 antigen.",,"['Wang, Xiao-Dong', 'Gao, Ning-Ning', 'Diao, Yu-Wen', 'Liu, Yu', 'Gao, Dong', 'Li, Wang', 'Wan, Yan-Yan', 'Zhong, Jing-Jing', 'Jin, Guang-Yi']",,,,
,PMC,Structures of complexes formed by H5 influenza hemagglutinin with a potent broadly neutralizing human monoclonal antibody,http://dx.doi.org/10.1073/pnas.1510816112,PMC4522749,,,"H5N1 avian influenza viruses remain a threat to public health mainly because they can cause severe infections in humans. These viruses are widespread in birds, and they vary in antigenicity forming three major clades and numerous antigenic variants. The most important features of the human monoclonal antibody FLD194 studied here are its broad specificity for all major clades of H5 influenza HAs, its high affinity, and its ability to block virus infection, in vitro and in vivo. As a consequence, this antibody may be suitable for anti-H5 therapy and as a component of stockpiles, together with other antiviral agents, for health authorities to use if an appropriate vaccine was not available. Our mutation and structural analyses indicate that the antibody recognizes a relatively conserved site near the membrane distal tip of HA, near to, but distinct from, the receptor-binding site. Our analyses also suggest that the mechanism of infectivity neutralization involves prevention of receptor recognition as a result of steric hindrance by the Fc part of the antibody. Structural analyses by EM indicate that three Fab fragments are bound to each HA trimer. The structure revealed by X-ray crystallography is of an HA monomer bound by one Fab. The monomer has some similarities to HA in the fusion pH conformation, and the monomer’s formation, which results from the presence of isopropanol in the crystallization solvent, contributes to considerations of the process of change in conformation required for membrane fusion.",,"['Xiong, Xiaoli', 'Corti, Davide', 'Liu, Junfeng', 'Pinna, Debora', 'Foglierini, Mathilde', 'Calder, Lesley J.', 'Martin, Stephen R.', 'Lin, Yi Pu', 'Walker, Philip A.', 'Collins, Patrick J.', 'Monne, Isabella', 'Suguitan, Amorsolo L.', 'Santos, Celia', 'Temperton, Nigel J.', 'Subbarao, Kanta', 'Lanzavecchia, Antonio', 'Gamblin, Steven J.', 'Skehel, John J.']",,,,
,PMC,Animal Models of Respiratory Syncytial Virus Infection and Disease,http://dx.doi.org/10.1016/j.coviro.2015.06.003,PMC4699663,,,"The study of human respiratory syncytial virus pathogenesis and immunity has been hampered by its exquisite host specificity, and the difficulties encountered in adapting this virus to a murine host. The reasons for this obstacle are not well understood, but appear to reflect, at least in part, the inability of the virus to block the interferon response in any but the human host. This review addresses some of the issues encountered in mouse models of respiratory syncytial virus infection, and describes the advantages and disadvantages of alternative model systems.",,"['Sacco, Randy E.', 'Durbin, Russell K.', 'Durbin, Joan E.']",,,,
,PMC,Contrasted patterns of variation and evolutionary convergence at the antiviral OAS1 gene in old world primates,http://dx.doi.org/10.1007/s00251-015-0855-0,PMC4809017,,,"The oligoadenylate synthetase 1 (OAS1) enzyme acts as an innate sensor of viral infection and plays a major role in the defense against a wide diversity of viruses. Polymorphisms at OAS1 have been shown to correlate with differential susceptibility to several infections of great public health significance, including hepatitis C virus, SARS coronavirus, and West Nile virus. Population genetics analyses in hominoids have revealed interesting evolutionary patterns. In Central African chimpanzee, OAS1 has evolved under long-term balancing selection, resulting in the persistence of polymorphisms since the origin of hominoids, whereas human populations have acquired and retained OAS1 alleles from Neanderthal and Denisovan origin. We decided to further investigate the evolution of OAS1 in primates by characterizing intra-specific variation in four species commonly used as models in infectious disease research: the rhesus macaque, the cynomolgus macaque, the olive baboon, and the Guinea baboon. In baboons, OAS1 harbors a very low level of variation. In contrast, OAS1 in macaques exhibits a level of polymorphism far greater than the genomic average, which is consistent with the action of balancing selection. The region of the enzyme that directly interacts with viral RNA, the RNA-binding domain, contains a number of polymorphisms likely to affect the RNA-binding affinity of OAS1. This strongly suggests that pathogen-driven balancing selection acting on the RNA-binding domain of OAS1 is maintaining variation at this locus. Interestingly, we found that a number of polymorphisms involved in RNA-binding were shared between macaques and chimpanzees. This represents an unusual case of convergent polymorphism.",,"['Fish, Ian', 'Boissinot, Stéphane']",,,,
,PMC,The multifaceted biology of plasmacytoid dendritic cells,http://dx.doi.org/10.1038/nri3865,PMC4808588,,,"Plasmacytoid dendritic cells (pDCs) are a unique dendritic cell subset that specializes in the production of type I interferons (IFNs). pDCs promote antiviral immune responses and have been implicated in the pathogenesis of autoimmune diseases characterized by a type I IFN signature. However, pDCs can also induce tolerogenic immune responses. Here, we review recent progress from the field of pDC biology, focusing on: the molecular mechanisms that regulate pDC development and functions; the pathways involved in their sensing of pathogens and endogenous nucleic acids; the function of pDCs at mucosal sites; and their roles in infections, autoimmunity and cancer.",,"['Swiecki, Melissa', 'Colonna, Marco']",,,,
,PMC,"DNA vaccines targeting heavy chain C-terminal fragments of Clostridium botulinum neurotoxin serotypes A, B, and E induce potent humoral and cellular immunity and provide protection from lethal toxin challenge",http://dx.doi.org/10.1080/21645515.2015.1066051,PMC4635847,,,"Botulinum neurotoxins (BoNTs) are deadly, toxic proteins produced by the bacterium Clostridium botulinum that can cause significant diseases in humans. The use of the toxic substances as potential bioweapons has raised concerns by the Centers for Disease Control and Prevention and the United States Military. Currently, there is no licensed vaccine to prevent botulinum intoxication. Here we present an immunogenicity study to evaluate the efficacy of novel monovalent vaccines and a trivalent cocktail DNA vaccine targeting the heavy chain C-terminal fragments of Clostridium botulinum neurotoxin serotypes A, B, and E. These synthetic DNA vaccines induced robust humoral and polyfunctional CD4(+) T-cell responses which fully protected animals against lethal challenge after just 2 immunizations. In addition, naïve animals administered immunized sera mixed with the lethal neurotoxin were 100% protected against intoxication. The data demonstrate the protective efficacy induced by a combinative synthetic DNA vaccine approach. This study has importance for the development of vaccines that provide protective immunity against C. botulinum neurotoxins and other toxins.",,"['Scott, Veronica L', 'Villarreal, Daniel O', 'Hutnick, Natalie A', 'Walters, Jewell N', 'Ragwan, Edwin', 'Bdeir, Khalil', 'Yan, Jian', 'Sardesai, Niranjan Y', 'Finnefrock, Adam C', 'Casimiro, Danilo R', 'Weiner, David B']",,,,
,PMC,Structural basis and functional analysis of the SARS coronavirus nsp14–nsp10 complex,http://dx.doi.org/10.1073/pnas.1508686112,PMC4522806,,,"Nonstructural protein 14 (nsp14) of coronaviruses (CoV) is important for viral replication and transcription. The N-terminal exoribonuclease (ExoN) domain plays a proofreading role for prevention of lethal mutagenesis, and the C-terminal domain functions as a (guanine-N7) methyl transferase (N7-MTase) for mRNA capping. The molecular basis of both these functions is unknown. Here, we describe crystal structures of severe acute respiratory syndrome (SARS)-CoV nsp14 in complex with its activator nonstructural protein10 (nsp10) and functional ligands. One molecule of nsp10 interacts with ExoN of nsp14 to stabilize it and stimulate its activity. Although the catalytic core of nsp14 ExoN is reminiscent of proofreading exonucleases, the presence of two zinc fingers sets it apart from homologs. Mutagenesis studies indicate that both these zinc fingers are essential for the function of nsp14. We show that a DEEDh (the five catalytic amino acids) motif drives nucleotide excision. The N7-MTase domain exhibits a noncanonical MTase fold with a rare β-sheet insertion and a peripheral zinc finger. The cap-precursor guanosine-P3-adenosine-5′,5′-triphosphate and S-adenosyl methionine bind in proximity in a highly constricted pocket between two β-sheets to accomplish methyl transfer. Our studies provide the first glimpses, to our knowledge, into the architecture of the nsp14–nsp10 complex involved in RNA viral proofreading.",,"['Ma, Yuanyuan', 'Wu, Lijie', 'Shaw, Neil', 'Gao, Yan', 'Wang, Jin', 'Sun, Yuna', 'Lou, Zhiyong', 'Yan, Liming', 'Zhang, Rongguang', 'Rao, Zihe']",,,,
,PMC,High prevalence and diversity of bovine astroviruses in the faeces of healthy and diarrhoeic calves in South West Scotland,http://dx.doi.org/10.1016/j.vetmic.2015.05.002,PMC4464496,25979841,CC BY,"Astroviruses (AstV) are single-stranded, positive-sense RNA viruses and one of the major causes of infant diarrhoea worldwide. Diarrhoea is a common and important cause of morbidity and mortality in calves; therefore, we investigated whether the presence of AstV is associated with calf diarrhoea. We identified diverse AstV lineages from faecal samples of both healthy and diarrhoeic calves and healthy adult cattle in South West Scotland. AstV was common in calves (present in 74% (85/115) of samples) but uncommon in adult cattle (present in 15% (3/20) of samples). No association was found between the presence of AstV and calf diarrhoea or the presence of a specific AstV lineage and calf diarrhoea. AstV was strongly associated with the presence of rotavirus Group A (RVA), and a protective effect of age was evident for both AstV and RVA. Co-infections with multiple AstV lineages were detected in several calves and serial infection with different viruses could also be seen by longitudinal sampling of individuals. In summary, our study found genotypically diverse AstV in the faeces of calves in South West Scotland. However, no association was identified between AstV and calf diarrhoea, which suggests the virus does not play a primary role in the aetiology of calf diarrhoea in the group studied.",2015 Jul 9,"['Sharp, Colin P.', 'Gregory, William F.', 'Mason, Colin', 'Bronsvoort, Barend M. deC', 'Beard, Philippa M.']",Vet Microbiol,,,
,PMC,Global Handwashing Day 2012: a qualitative content analysis of Chinese social media reaction to a health promotion event,http://dx.doi.org/10.5365/WPSAR.2015.6.2.003,PMC4675155,,,"BACKGROUND: Global Handwashing Day (GHD) is a handwashing promotion campaign organized by the Global Public-Private Partnership of Handwashing with Soap. In China, it has been promoted by the Chinese public health authorities, international organizations and multinational corporations through various channels including social media such as Sina Weibo, the leading Chinese microblogging site similar to Twitter. The objective of this study is to qualitatively assess Chinese social media users’ reactions to a health promotion campaign using Global Handwashing Day (GHD) 2012 as an example. METHODS: We conducted a qualitative content analysis of 552 Weibo posts generated on GHD 2012 by Weibo users with 1000 or more followers with the Chinese keyword for “handwashing.” We categorized the Weibo posts into groups by keywords that frequently appeared in the data set. These groups were either exact reposts of an original post, or they conveyed similar information. RESULTS: We observed the interconnections between traditional media and social media in handwashing promotion. Social media were found to serve as amplifiers of contents provided by traditional media. We observed the contextualization of global hygiene messages in a unique national social media market in China. DISCUSSION: Our study showed that social media and traditional media are two interconnected arms of the GHD campaign in China. Our analysis demonstrated that public health campaigns in China can be evaluated using social media data. The themes and topics identified in this study will help public health practitioners evaluate future social media handwashing promotion campaigns.",,"['Fung, Isaac Chun-Hai', 'Cai, Jingxian', 'Hao, Yi', 'Ying, Yuchen', 'Chan, Benedict Shing Bun', 'Tse, Zion Tsz Ho', 'Fu, King-Wa']",,,,
,PMC,Role of neurons and glia in the CNS actions of the renin-angiotensin system in cardiovascular control,http://dx.doi.org/10.1152/ajpregu.00078.2015,PMC4591381,,,"Despite tremendous research efforts, hypertension remains an epidemic health concern, leading often to the development of cardiovascular disease. It is well established that in many instances, the brain plays an important role in the onset and progression of hypertension via activation of the sympathetic nervous system. Further, the activity of the renin-angiotensin system (RAS) and of glial cell-mediated proinflammatory processes have independently been linked to this neural control and are, as a consequence, both attractive targets for the development of antihypertensive therapeutics. Although it is clear that the predominant effector peptide of the RAS, ANG II, activates its type-1 receptor on neurons to mediate some of its hypertensive actions, additional nuances of this brain RAS control of blood pressure are constantly being uncovered. One of these complexities is that the RAS is now thought to impact cardiovascular control, in part, via facilitating a glial cell-dependent proinflammatory milieu within cardiovascular control centers. Another complexity is that the newly characterized antihypertensive limbs of the RAS are now recognized to, in many cases, antagonize the prohypertensive ANG II type 1 receptor (AT(1)R)-mediated effects. That being said, the mechanism by which the RAS, glia, and neurons interact to regulate blood pressure is an active area of ongoing research. Here, we review the current understanding of these interactions and present a hypothetical model of how these exchanges may ultimately regulate cardiovascular function.",,"['de Kloet, Annette D.', 'Liu, Meng', 'Rodríguez, Vermalí', 'Krause, Eric G.', 'Sumners, Colin']",,,,
,PMC,Immunological Features Underlying Viral Hemorrhagic Fevers,http://dx.doi.org/10.1016/j.coi.2015.06.003,PMC4593727,,,"Several enveloped RNA viruses of the arenavirus, bunyavirus, filovirus and flavivirus families are associated with a syndrome known as viral hemorrhagic fever (VHF). VHF is characterized by fever, vascular leakage, coagulation defects and multi organ system failure. VHF is currently viewed as a disease precipitated by viral suppression of innate immunity, which promotes systemic virus replication and excessive proinflammatory cytokine responses that trigger the manifestations of severe disease. However, the mechanisms by which immune dysregulation contributes to disease remain poorly understood. Infection of nonhuman primates closely recapitulates human VHF, notably Ebola and yellow fever, thereby providing excellent models to better define the immunological basis for this syndrome. Here we review the current state of our knowledge and suggest future directions that will better define the immunological mechanisms underlying VHF.",,"['Messaoudi, Ilhem', 'Basler, Christopher F.']",,,,
,PMC,Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients,http://dx.doi.org/10.1038/ismej.2015.99,PMC4681870,,,"Bacterial pneumonia is a major cause of morbidity and mortality in elderly. We hypothesize that dysbiosis between regular residents of the upper respiratory tract (URT) microbiome, that is balance between commensals and potential pathogens, is involved in pathogen overgrowth and consequently disease. We compared oropharyngeal microbiota of elderly pneumonia patients (n=100) with healthy elderly (n=91) by 16S-rRNA-based sequencing and verified our findings in young adult pneumonia patients (n=27) and young healthy adults (n=187). Microbiota profiles differed significantly between elderly pneumonia patients and healthy elderly (PERMANOVA, P<0.0005). Highly similar differences were observed between microbiota profiles of young adult pneumonia patients and their healthy controls. Clustering resulted in 11 (sub)clusters including 95% (386/405) of samples. We observed three microbiota profiles strongly associated with pneumonia (P<0.05) and either dominated by lactobacilli (n=11), Rothia (n=51) or Streptococcus (pseudo)pneumoniae (n=42). In contrast, three other microbiota clusters (in total n=183) were correlated with health (P<0.05) and were all characterized by more diverse profiles containing higher abundances of especially Prevotella melaninogenica, Veillonella and Leptotrichia. For the remaining clusters (n=99), the association with health or disease was less clear. A decision tree model based on the relative abundance of five bacterial community members in URT microbiota showed high specificity of 95% and sensitivity of 84% (89% and 73%, respectively, after cross-validation) for differentiating pneumonia patients from healthy individuals. These results suggest that pneumonia in elderly and young adults is associated with dysbiosis of the URT microbiome with bacterial overgrowth of single species and absence of distinct anaerobic bacteria. Whether the observed microbiome changes are a cause or a consequence of the development of pneumonia or merely coincide with disease status remains a question for future research.",,"['de Steenhuijsen Piters, Wouter A A', 'Huijskens, Elisabeth G W', 'Wyllie, Anne L', 'Biesbroek, Giske', 'van den Bergh, Menno R', 'Veenhoven, Reinier H', 'Wang, Xinhui', 'Trzciński, Krzysztof', 'Bonten, Marc J', 'Rossen, John W A', 'Sanders, Elisabeth A M', 'Bogaert, Debby']",,,,
,PMC,Engineering immunity in the mucosal niche against sexually transmitted infections,http://dx.doi.org/10.1002/wnan.1359,PMC6467227,,,"The mucosal surfaces of the genital tract are the site of entry to over 30 different bacterial, parasitic, and viral pathogens that are the cause of sexually transmitted infections (STIs) including HIV. Women and adolescent girls are more severely impacted by STIs than men due in part to a greater biological susceptibility for acquiring infections and differences in disease sequelae. While it is widely accepted that preventative vaccines against the most commonly transmitted STIs would have a major impact on decreasing the global health burden of STIs for women worldwide, several challenges preclude their development. The female genital tract is a complex niche of microflora, hormonal influences, and immune tissues and cells that result in a mucosal immune system that is distinct from other mucosal sites and from our systemic immune system. An appreciation of these differences and their effect on shaping mucosal immunity to sexually transmitted pathogens is an important determinant for the design of effective STI vaccines. Here we describe the anatomy and mucosal immune system of the female reproductive tract, and discuss bioengineering strategies to design mucosal vaccines that overcome delivery challenges and coordinate the presentation kinetics and compartmentalization of antigens and adjuvants to relevant mucosal immune cell subsets. In particular, we describe recent progress in understanding the role of specific mucosal dendritic cell subsets in facilitating immune responses to pathogenic microbes in the genital mucosa. We also discuss the development of pathogen-mimicking materials that may be useful for engineering protective immunity in this mucosal niche.",,"['Ramanathan, Renuka', 'Woodrow, Kim']",,,,
,PMC,Inferring influenza dynamics and control in households,http://dx.doi.org/10.1073/pnas.1423339112,PMC4517268,,,"Household-based interventions are the mainstay of public health policy against epidemic respiratory pathogens when vaccination is not available. Although the efficacy of these interventions has traditionally been measured by their ability to reduce the proportion of household contacts who exhibit symptoms [household secondary attack rate (hSAR)], this metric is difficult to interpret and makes only partial use of data collected by modern field studies. Here, we use Bayesian transmission model inference to analyze jointly both symptom reporting and viral shedding data from a three-armed study of influenza interventions. The reduction in hazard of infection in the increased hand hygiene intervention arm was 37.0% [8.3%, 57.8%], whereas the equivalent reduction in the other intervention arm was 27.2% [−0.46%, 52.3%] (increased hand hygiene and face masks). By imputing the presence and timing of unobserved infection, we estimated that only 61.7% [43.1%, 76.9%] of infections met the case criteria and were thus detected by the study design. An assessment of interventions using inferred infections produced more intuitively consistent attack rates when households were stratified by the speed of intervention, compared with the crude hSAR. Compared with adults, children were 2.29 [1.66, 3.23] times as infectious and 3.36 [2.31, 4.82] times as susceptible. The mean generation time was 3.39 d [3.06, 3.70]. Laboratory confirmation of infections by RT-PCR was only able to detect 79.6% [76.5%, 83.0%] of symptomatic infections, even at the peak of shedding. Our results highlight the potential use of robust inference with well-designed mechanistic transmission models to improve the design of intervention studies.",,"['Lau, Max S.Y.', 'Cowling, Benjamin J.', 'Cook, Alex R.', 'Riley, Steven']",,,,
,PMC,A G-quadruplex-binding macrodomain within the “SARS-unique domain” is essential for the activity of the SARS-coronavirus replication-transcription complex,http://dx.doi.org/10.1016/j.virol.2015.06.016,PMC4567502,,,"The multi-domain non-structural protein 3 of SARS-coronavirus is a component of the viral replication/transcription complex (RTC). Among other domains, it contains three sequentially arranged macrodomains: the X domain and subdomains SUD-N as well as SUD-M within the “SARS-unique domain”. The X domain was proposed to be an ADP-ribose-1″-phosphatase or a poly(ADP-ribose)-binding protein, whereas SUD-NM binds oligo(G)-nucleotides capable of forming G-quadruplexes. Here, we describe the application of a reverse genetic approach to assess the importance of these macrodomains for the activity of the SARS-CoV RTC. To this end, Renilla luciferase-encoding SARS-CoV replicons with selectively deleted macrodomains were constructed and their ability to modulate the RTC activity was examined. While the SUD-N and the X domains were found to be dispensable, the SUD-M domain was crucial for viral genome replication/transcription. Moreover, alanine replacement of charged amino-acid residues of the SUD-M domain, which are likely involved in G-quadruplex-binding, caused abrogation of RTC activity.",,"['Kusov, Yuri', 'Tan, Jinzhi', 'Alvarez, Enrique', 'Enjuanes, Luis', 'Hilgenfeld, Rolf']",,,,
,PMC,Molecular Mechanisms and Timing of Cortical Immune Activation in Schizophrenia,http://dx.doi.org/10.1176/appi.ajp.2015.15010019,PMC5063256,,,"OBJECTIVE: Immune-related abnormalities are commonly reported in schizophrenia, including higher mRNA levels for the viral restriction factor interferon-induced transmembrane protein (IFITM) in the prefrontal cortex. The authors sought to clarify whether higher IFITM mRNA levels and other immune-related disturbances in the prefrontal cortex are the consequence of an ongoing molecular cascade contributing to immune activation or the reflection of a long-lasting maladaptive response to an in utero immune-related insult. METHOD: Quantitative polymerase chain reaction was employed to measure mRNA levels for immune-related cytokines and transcriptional regulators, including those reported to regulate IFITM expression, in the prefrontal cortex from 62 schizophrenia and 62 healthy subjects and from adult mice exposed prenatally to maternal immune activation or in adulthood to the immune stimulant poly(I:C). RESULTS: Schizophrenia subjects had markedly higher mRNA levels for interleukin 6 (IL-6) (+379%) and interferon-β (+29%), which induce IFITM expression; lower mRNA levels for Schnurri-2 (−10%), a transcriptional inhibitor that lowers IFITM expression; and higher mRNA levels for nuclear factor-κB (+86%), a critical transcription factor that mediates cytokine regulation of immune-related gene expression. In adult mice that received daily poly(I:C) injections, but not in offspring with prenatal exposure to maternal immune activation, frontal cortex mRNA levels were also markedly elevated for IFITM (+304%), multiple cytokines including IL-6 (+493%), and nuclear factor-κB (+151%). CONCLUSIONS: These data suggest that higher prefrontal cortex IFITM mRNA levels in schizophrenia may be attributable to adult, but not prenatal, activation of multiple immune markers and encourage further investigation into the potential role of these and other immune markers as therapeutic targets in schizophrenia.",,"['Volk, David W.', 'Chitrapu, Anjani', 'Edelson, Jessica R.', 'Roman, Kaitlyn M.', 'Moroco, Annie E.', 'Lewis, David A.']",,,,
,PMC,Hunting Viral Receptors Using Haploid Cells,http://dx.doi.org/10.1146/annurev-virology-100114-055119,PMC4982367,,,"Viruses have evolved intricate mechanisms to gain entry into the host cell. Identification of critical receptors has enabled insights into virus particle internalization, host and tissue tropism, and viral pathogenesis. In this review we discuss the most commonly employed methods for virus receptor discovery, specifically highlighting the use of forward genetic screens in human haploid cells. The ability to generate true knockout alleles at high saturation provides a sensitive means to study virus-host interactions. As an example, haploid genetic screens identified the lysosomal proteins, NPC1 and LAMP1, as intracellular receptors for Ebola virus and Lassa virus, respectively. From these studies emerges the notion that receptor usage by these viruses is highly dynamic involving a programmed switch from cell surface receptor to intracellular receptor. Broad application of genetic knockout approaches will chart functional landscapes of receptors and endocytic pathways hijacked by viruses.",,"['Pillay, Sirika', 'Carette, Jan E.']",,,,
,PMC,Melting of duplex DNA in the absence of ATP by NS3 helicase domain through specific interaction with a single-strand/double-strand junction,http://dx.doi.org/10.1021/acs.biochem.5b00214,PMC5111830,,,"Helicases unwind double-stranded nucleic acids, remove secondary structures from single-stranded nucleic acids, and remove proteins bound to nucleic acids. For many helicases, the mechanisms for these different functions share the ability to translocate with a directional bias as a result of ATP binding and hydrolysis. The nonstructural protein 3 (NS3) is an essential enzyme expressed by the hepatitis C virus (HCV) and is known to catalyze the unwinding of both DNA and RNA substrates in a 3′-to-5′ direction. We investigated the role of nucleic acid binding in the unwinding mechanism by examining ATP-independent unwinding. We observed that even in the absence of ATP, NS3 helicase domain (NS3h) unwound duplexes only when they contained a 3′-tail (i.e., 3′-to-5′ directionality). Blunt-ended duplexes and 5′-tailed duplexes were not melted even in the presence of a large excess concentration of the protein. NS3h was found to diffuse rapidly along single-stranded DNA at a rate of 30 nt(2)·s(−1). Upon encountering an appropriate single-strand/double-strand (ss/ds) junction, NS3h slowly melted the duplex under conditions with excess protein concentration relative to DNA concentration. When a biotin-streptavidin block was placed into the ssDNA region, no melting of DNA was observed, suggesting that NS3h must diffuse along the ssDNA, and that the streptavidin blocked the diffusion. We conclude that the specific interaction between NS3h and the ss/dsDNA junction, coupled with diffusion allows binding energy to melt duplex DNA with a directional bias. Alternatively, we found that the full-length NS3 protein did not exhibit strict directionality and was dependent on duplex DNA length. NS3 was able to unwind the duplex even in the presence of the biotin-streptavidin block. We propose a non-canonical model of unwinding for NS3 in which the enzyme binds directly to the duplex via protein-protein interactions to melt the substrate.",,"['Reynolds, Kimberly A.', 'Cameron, Craig E.', 'Raney, Kevin D.']",,,,
,PMC,Conformational changes of the HsDHODH N-terminal Microdomain via DEER Spectroscopy,http://dx.doi.org/10.1021/acs.jpcb.5b01706,PMC4814773,,,"The human enzyme dihydroorotate dehydrogenase (HsDHODH) has been studied for being a target for development of new antineoplasic and antiproliferative drugs. The synthetic peptide N-t(DH) represents the N-terminal microdomain of this enzyme, responsible for anchoring it to the inner mitochondrial membrane. Also, it is known to harbor quinones that are essential for enzyme catalysis. Here we report structural features of the peptide/membrane interactions obtained by using CD and DEER spectroscopic techniques, both in micelles and in lipid vesicles. The data revealed different peptide conformational states in micelles and liposomes, which could suggest that this microdomain acts in specific regions or areas of the mitochondria, which can be related with the control of the quinone access to the HsDHODH active site. This is the first study to report on conformational changes of the HsDHODH N-terminal microdomain through a combination of CD and DEER spectroscopic techniques.",,"['Vicente, Eduardo F.', 'Sahu, Indra D.', 'Costa-Filho, Antonio J.', 'Cilli, Eduardo M.', 'Lorigan, Gary A.']",,,,
,PMC,Re-emerging Middle East respiratory syndrome coronavirus: The hibernating bat hypothesis,http://dx.doi.org/10.4103/1817-1737.160847,PMC4518356,26229568,CC BY-NC-SA,,2015 Jul-Sep,"['Fakhoury, Hana', 'Hajeer, Ali']",Ann Thorac Med,,,
,PMC,A comparative proteomic study of plasma in feline pancreatitis and pancreatic carcinoma using 2-dimensional gel electrophoresis to identify diagnostic biomarkers: A pilot study,,PMC4445510,,,"While pancreatitis is now recognized as a common ailment in cats, the diagnosis remains challenging due to discordant results and suboptimal sensitivity of ultrasound and specific feline pancreatic lipase (Spec fPL) assay. Pancreatitis also shares similar clinical features with pancreatic carcinoma, a rare but aggressive disease with a grave prognosis. The objective of this pilot study was to compare the plasma proteomes of normal healthy cats (n = 6), cats with pancreatitis (n = 6), and cats with pancreatic carcinoma (n = 6) in order to identify potential new biomarkers of feline pancreatic disease. After plasma protein separation by 2-dimensional gel electrophoresis, protein spots were detected by Coomassie Brilliant Blue G-250 staining and identified by mass spectrometry. Alpha-1-acid glycoprotein (AGP), apolipoprotein-A1 (Apo-A1), and apolipoprotein-A1 precursor (Pre Apo-A1) appeared to be differentially expressed, which suggests the presence of a systemic acute-phase response and alteration of lipid metabolism in cats with pancreatic disease. Future studies involving greater case numbers are needed in order to assess the utility of these proteins as potential biomarkers. More sensitive proteomic techniques may also be helpful in detecting significant but low-abundance proteins.",,"['Meachem, Melissa D.', 'Snead, Elisabeth R.', 'Kidney, Beverly A.', 'Jackson, Marion L.', 'Dickinson, Ryan', 'Larson, Victoria', 'Simko, Elemir']",,,,
,PMC,Ebola virus entry into host cells: identifying therapeutic strategies,http://dx.doi.org/10.1007/s40588-015-0021-3,PMC4617201,,,"Filoviruses cause severe hemorrhagic fever in humans. The archetypal virus of this group, Ebola virus, is responsible for the current filovirus epidemic in West Africa. Filoviruses infect most mammalian cells, resulting in broad species tropism and likely contributing to rapid spread of virus throughout the body. A thorough understanding of filovirus entry events will facilitate the development of therapeutics against these critical steps in the viral life cycle. This review summarizes the current understanding of filovirus entry and discusses some of the recent advancements in therapeutic strategies that target entry.",,"['Rhein, Bethany A.', 'Maury, Wendy J.']",,,,
,PMC,Differential Expression of miR-499 and Validation of Predicted Target Genes in the Testicular Tissue of Swine at Different Developmental Stages,http://dx.doi.org/10.1089/dna.2014.2728,PMC4504256,,,"microRNAs (miRNAs) represent a newly identified class of nonprotein-coding ∼22 nt small RNA that plays important roles in multiple biological processes by degrading targeted mRNA or repressing mRNA translation. This study observed the morphology of swine testicular tissue at different developmental stages (including 1-day old, 1–7 month old) by Hematoxylin-eosin staining. We also examined the expression of miR-499 and its target genes (CYLC1, DMRT1, QKI, XRN2, ZNF313) in samples of tissue slices using quantitative reverse-transcription polymerase chain reaction, which showed that miR-499 had a significant negative correlation with QKI gene. Then, the proteins of QKI gene expression were determined by western blot, which were consistent with results of quantitative polymerase chain reaction (qPCR) detection. Therefore, the luciferase reporter gene system was used to verify correlation between miR-499 and QKI gene. Activity of luciferase was significantly lower in miR-499 co-transfected with pmiR-RB-REPORT-QKI-WT group than the miR-499 co-transfected with pmiR-RB-REPORT-QKI-mut/si groups, indicating that target sequence of miR-499 existed in 3′UTR of QKI gene. Furthermore, the expressions of miR-499 and QKI were detected in testicular cells that were transfected with miR-499, miR-499 negative control and untreated. The results showed that the diameter of convoluted seminiferous tubule growth increased with age. Significantly different expressions of miR-499 and its target genes were found in swine testicular tissue at different developmental stages (p<0.05), overexpressing miR-499 analysis, suggesting that miR-499 was negatively correlated to the expression of QKI (p<0.05). In conclusion, QKI is a target gene of miR-499.",,"['Zhang, Xiaojun', 'Li, Chuanmin', 'Liu, Xin', 'Lu, Chunyan', 'Bai, Chunyan', 'Zhao, Zhihui', 'Sun, Boxing']",,,,
,PMC,Compromised natural killer cells in pulmonary embolism,,PMC4555721,,,"Objective: The high morbidity, mortality and misdiagnosis rate render pulmonary embolism (PE) as a worldwide health problem. However, the etiology and pathogenesis of this disease have not been well characterized. Increasing studies indicate infection and immunity play a crucial role in PE. Natural killer (NK) cells act as a bridge between the innate immune and acquired immune. This study aimed to investigate the possible function of NK cells in PE. Methods: Human cDNA microarray analysis was employed to detect genes associated with NK cells in peripheral blood mononuclear cells (PBMCs). Random variance model corrected t-test was used for statistical analysis of differential gene expression. Flow cytometry was performed to detect the CD16+CD56+ NK cells. Results: In the present study, based on gene expression microarray analysis, we showed four inhibitory receptors (KLRB1, KLRD1, KLRF1, KLRG1) and four activating receptors (KLRC1, KLRC3, KLRK1 and NCR1) on NK cells were remarkably down-regulated and the cytological experiment demonstrated the proportion of CD16+CD56+ NK cells among PBMCs decreased in the PE group. Conclusions: We confirmed the presence of reduced expression of critical activating as well as inhibitory NK cell receptors and low proportion of CD16+CD56+ NK cells in PE. The consistence between genomic and cytological examination suggests compromised NK cells may contribute to the pathogenesis of PE.",,"['Zhang, Xiaoyu', 'Wang, Qiang', 'Shen, Yuqin', 'Song, Haoming', 'Gong, Zhu', 'Wang, Lemin']",,,,
,PMC,Assessment of an Orofacial Operant Pain Assay as a Preclinical Tool for Evaluating Analgesic Efficacy in Rodents,,PMC4521578,,,"A model system capable of providing clinically relevant analgesic doses with minimal trauma has been elusive in laboratory animal medicine. Our laboratory has developed an orofacial operant pain system that effectively discriminates between nonnoxious and noxious thermal stimuli in rats and mice. Male and female rats (Crl:SD) and mice (Crl:SKR-HR(hr)) were trained to perform a task (placing their face through an opening and having their cheeks stay in contact with thermodes) to receive a reward (a solution of sweetened condensed milk). Currently accepted doses of buprenorphine were tested by using a crossover design. Pain was induced in both species by sensitizing the depilated skin over both cheeks with capsaicin cream or by creating a surgical incision (rats only) and then allowing the animals to contact a temperature-regulated thermode while obtaining a reward. Optimal antinociceptive doses included 0.05 and 0.1 mg/kg in male mice but only 0.05 mg/kg in female mice. In rats, optimal antinociceptive doses included 0.03 and 0.05 mg/kg for male rats but only 0.03 mg/kg for female rats. The 2 pain-induction models in rats (capsaicin cream and surgical incision) did not differ. Our orofacial operant pain assay can determine clinically relevant analgesic doses for rodents in a preclinical assay. The automated, investigator-independent nature of the assay, in conjunction with its high sensitivity, makes this method an improvement over traditional noninvasive methods, providing better data for developing optimal analgesic recommendations for rats and mice.",,"['Ramirez, Harvey E', 'Queeney, Timothy J', 'Dunbar, Misha L', 'Eichner, Michael C', 'Del Castillo, Dania I', 'Battles, August H', 'Neubert, John K']",,,,
,PMC,Interleukin-35: Expanding Its Job Profile,http://dx.doi.org/10.1089/jir.2015.0015,PMC4507123,,,"Counter-regulation afforded by specialized regulatory cell populations and immunosuppressive cytokines is critical for balancing immune outcome. The inhibitory potential of the established suppressive cytokines, IL-10 and TGFβ, has been well elucidated in diverse inflammatory scenarios in conjunction with their key roles in Treg development and function. Despite the early predictions for an immunomodulatory role for the Ebi3/p35 heterodimer in placental trophoblasts, IL-35 biology remained elusive until 2007 when it was established as a Treg-restricted inhibitory cytokine. Since then, Treg-derived IL-35 has been shown to exhibit its suppressive activities in a range of autoimmune diseases and cancer models. Recent studies are beginning to explore other cellular sources of IL-35, such as Bregs and CD8(+) Tregs. Despite these new cellular sources and targets, the mode of IL-35 suppression remains restricted to inhibition of proliferation and induction of an IL-35-producing induced regulatory T cell population referred to as iTr35. In this review, we explore the early beginnings, status quo, and future prospects of IL-35 biology. The unparalleled opportunity of targeting multiple immunosuppressive populations (Tregs, Bregs, CD8(+) Tregs) through IL-35 is highly exciting and offers tremendous promise from a translational standpoint, particularly for cancer immunotherapies.",,"['Sawant, Deepali V.', 'Hamilton, Kristia', 'Vignali, Dario A.A.']",,,,
,PMC,A rare cause of acute flaccid paralysis: Human coronaviruses,http://dx.doi.org/10.4103/1817-1745.165716,PMC4611905,26557177,CC BY-NC-SA,"Acute flaccid paralysis (AFP) is a life-threatening clinical entity characterized by weakness in the whole body muscles often accompanied by respiratory and bulbar paralysis. The most common cause is Gullian–Barre syndrome, but infections, spinal cord diseases, neuromuscular diseases such as myasthenia gravis, drugs and toxins, periodic hypokalemic paralysis, electrolyte disturbances, and botulism should be considered as in the differential diagnosis. Human coronaviruses (HCoVs) cause common cold, upper and lower respiratory tract disease, but in the literature presentation with the lower respiratory tract infection and AFP has not been reported previously. In this study, pediatric case admitted with lower respiratory tract infection and AFP, who detected for HCoV 229E and OC43 co-infection by the real-time polymerase chain reaction, has been reported for the first time.",2015 Jul-Sep,"['Turgay, Cokyaman', 'Emine, Tekin', 'Ozlem, Koken', 'Muhammet, S. Paksu', 'Haydar, A. Tasdemir']",J Pediatr Neurosci,,,
,PMC,Application of Behavioral Theories to Disaster and Emergency Health Preparedness: A Systematic Review,http://dx.doi.org/10.1371/currents.dis.31a8995ced321301466db400f1357829,PMC4494855,26203400,CC BY,"Background: Preparedness for disasters and emergencies at individual, community and organizational levels could be more effective tools in mitigating (the growing incidence) of disaster risk and ameliorating their impacts. That is, to play more significant roles in disaster risk reduction (DRR). Preparedness efforts focus on changing human behaviors in ways that reduce people’s risk and increase their ability to cope with hazard consequences. While preparedness initiatives have used behavioral theories to facilitate DRR, many theories have been used and little is known about which behavioral theories are more commonly used, where they have been used, and why they have been preferred over alternative behavioral theories. Given that theories differ with respect to the variables used and the relationship between them, a systematic analysis is an essential first step to answering questions about the relative utility of theories and providing a more robust evidence base for preparedness components of DRR strategies. The goal of this systematic review was to search and summarize evidence by assessing the application of behavioral theories to disaster and emergency health preparedness across the world. Methods: The protocol was prepared in which the study objectives, questions, inclusion and exclusion criteria, and sensitive search strategies were developed and pilot-tested at the beginning of the study. Using selected keywords, articles were searched mainly in PubMed, Scopus, Mosby’s Index (Nursing Index) and Safetylit databases. Articles were assessed based on their titles, abstracts, and their full texts. The data were extracted from selected articles and results were presented using qualitative and quantitative methods. Results: In total, 2040 titles, 450 abstracts and 62 full texts of articles were assessed for eligibility criteria, whilst five articles were archived from other sources, and then finally, 33 articles were selected. The Health Belief Model (HBM), Extended Parallel Process Model (EPPM), Theory of Planned Behavior (TPB) and Social Cognitive Theories were most commonly applied to influenza (H1N1 and H5N1), floods, and earthquake hazards. Studies were predominantly conducted in USA (13 studies). In Asia, where the annual number of disasters and victims exceeds those in other continents, only three studies were identified. Overall, the main constructs of HBM (perceived susceptibility, severity, benefits, and barriers), EPPM (higher threat and higher efficacy), TPB (attitude and subjective norm), and the majority of the constructs utilized in Social Cognitive Theories were associated with preparedness for diverse hazards. However, while all the theories described above describe the relationships between constituent variables, with the exception of research on Social Cognitive Theories, few studies of other theories and models used path analysis to identify the interdependence relationships between the constructs described in the respective theories/models. Similarly, few identified how other mediating  variables could influence disaster and emergency preparedness.  Conclusions: The existing evidence on the application of behavioral theories and models to disaster and emergency preparedness is chiefly from developed countries. This raises issues regarding their utility in countries, particularly in Asisa and the Middle East, where cultural characteristics are very different to those prevailing in the Western countries in which theories have been developed and tested. The theories and models discussed here have been applied predominantly to disease outbreaks and natural hazards, and information on their utility as guides to preparedness for man-made hazards is lacking. Hence, future studies related to behavioral theories and models addressing preparedness need to target developing countries where disaster risk  and the consequent need for preparedness is high. A need for additional work on demonstrating the relationships of variables and constructs, including more clearly articulating roles for mediating effects was also identified in this analysis.",2015 Jul 1,"['Ejeta, Luche Tadesse', 'Ardalan, Ali', 'Paton, Douglas']",PLoS Curr,,,
,PMC,"CDC's Early Response to a Novel Viral Disease, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), September 2012–May 2014",,PMC4547580,,,"The first ever case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was reported in September 2012. This report describes the approaches taken by CDC, in collaboration with the World Health Organization (WHO) and other partners, to respond to this novel virus, and outlines the agency responses prior to the first case appearing in the United States in May 2014. During this time, CDC's response integrated multiple disciplines and was divided into three distinct phases: before, during, and after the initial activation of its Emergency Operations Center. CDC's response to MERS-CoV required a large effort, deploying at least 353 staff members who worked in the areas of surveillance, laboratory capacity, infection control guidance, and travelers' health. This response built on CDC's experience with previous outbreaks of other pathogens and provided useful lessons for future emerging threats.",,"['Williams, Holly Ann', 'Dunville, Richard L.', 'Gerber, Susan I.', 'Erdman, Dean D.', 'Pesik, Nicki', 'Kuhar, David', 'Mason, Karen A.', 'Haynes, Lia', 'Rotz, Lisa', 'St. Pierre, Jeanette', 'Poser, Sarah', 'Bunga, Sudhir', 'Pallansch, Mark A.', 'Swerdlow, David L.']",,,,
,PMC,A Message from the Editor,,PMC4547575,,,,,"Shaw, Frederic E.",,,,
,PMC,Targeting Transmission Pathways for Emerging Zoonotic Disease Surveillance and Control,http://dx.doi.org/10.1089/vbz.2013.1563,PMC4507309,,,"We used literature searches and a database of all reported emerging infectious diseases (EIDs) to analyze the most important transmission pathways (e.g., vector-borne, aerosol droplet transmitted) for emerging zoonoses. Our results suggest that at the broad scale, the likelihood of transmission occurring through any one pathway is approximately equal. However, the major transmission pathways for zoonoses differ widely according to the specific underlying drivers of EID events (e.g., land-use change, agricultural intensification). These results can be used to develop better targeting of surveillance for, and more effective control of newly emerged zoonoses in regions under different underlying pressures that drive disease emergence.",,"['Loh, Elizabeth H.', 'Zambrana-Torrelio, Carlos', 'Olival, Kevin J.', 'Bogich, Tiffany L.', 'Johnson, Christine K.', 'Mazet, Jonna A. K.', 'Karesh, William', 'Daszak, Peter']",,,,
,PMC,Design and Antigenic Epitopes Prediction of a New Trial Recombinant Multiepitopic Rotaviral Vaccine: In Silico Analyses,http://dx.doi.org/10.1089/vim.2014.0152,PMC4507124,,,"Rotavirus is the major etiologic factor of severe diarrheal disease. Natural infection provides protection against subsequent rotavirus infection and diarrhea. This research presents a new vaccine designed based on computational models. In this study, three types of epitopes are considered—linear, conformational, and combinational—in a proposed model protein. Several studies on rotavirus vaccines have shown that VP6 and VP4 proteins are good candidates for vaccine production. In the present study, a fusion protein was designed as a new generation of rotavirus vaccines by bioinformatics analyses. This model-based study using ABCpred, BCPREDS, Bcepred, and Ellipro web servers showed that the peptide presented in this article has the necessary properties to act as a vaccine. Prediction of linear B-cell epitopes of peptides is helpful to investigate whether these peptides are able to activate humoral immunity.",,"['Jafarpour, Sima', 'Ayat, Hoda', 'Ahadi, Ali Mohammad']",,,,
,PMC,Patient-Centred Coordinated Care in Times of Emerging Diseases and Epidemics: Contribution of the IMIA Working Group on Patient Safety,http://dx.doi.org/10.15265/IY-2015-019,PMC4587040,,,"OBJECTIVES: In this paper the researchers describe how existing health information technologies (HIT) can be repurposed and new technologies can be innovated to provide patient-centered care to individuals affected by new and emerging diseases. METHODS: The researchers conducted a focused review of the published literature describing how HIT can be used to support safe, patient-centred, coordinated care to patients who are affected by Ebola (an emerging disease). RESULTS: New and emerging diseases present opportunities for repurposing existing technologies and for stimulating the development of new HIT innovation. Innovative technologies may be developed such as new software used for tracking patients during new or emerging disease outbreaks or by repurposing and extending existing technologies so they can be used to support patients, families and health professionals who may have been exposed to a disease. The paper describes the development of new technologies and the repurposing and extension of existing ones (such as electronic health records) using the most recent outbreak of Ebola as an example.",,"['Borycki, E.', 'Cummings, E.', 'Dexheimer, J. W.', 'Gong, Y.', 'Kennebeck, S.', 'Kushniruk, A.', 'Kuziemsky, C.', 'Saranto, K.', 'Weber, J.', 'Takeda, H.']",,,,
,PMC,Health Information Technology Challenges to Support Patient-Centered Care Coordination,http://dx.doi.org/10.15265/IY-2015-028,PMC4587038,,,"OBJECTIVES: To provide an editorial introduction to the 2015 IMIA Yearbook of Medical Informatics. METHODS: We provide a brief overview of the 2015 special topic “Patient-Centered Care Coordination”, discuss the addition of two new sections to the Yearbook, Natural Language Processing and Public Health & Epidemiology Informatics, and present our editorial plans for the upcoming celebration of the 25th anniversary of the Yearbook. RESULTS: Care delivery currently occurs through the processing of complex clinical pathways designed for increasingly multi-morbid patients by various practitioners in different settings. To avoid the consequences of the fragmentation of services, care should be organized to coordinate all providers, giving them the opportunity to share the same holistic view of the patient’s condition, and to be informed of the planned clinical pathway that establishes the roles and interventions of each one. The adoption and use of electronic health records (EHRs) is a solution to address health information sharing and care coordination challenges. However, while EHRs are necessary, they are not sufficient to achieve care coordination, creating information availability does not mean the information will be accessed. This edition of the Yearbook acknowledges the fact that health information technology (HIT), and EHRs in particular, are not yet fully addressing the challenges in care coordination. Emerging trends, tools, and applications of HIT to support care coordination are presented through the keynote paper, survey papers, and working group contributions. CONCLUSIONS: In 2015, the IMIA Yearbook has been extended to emphasize two fields of biomedical informatics through new sections. Next year, the 25(th) anniversary of the Yearbook will be celebrated in grand style! A special issue with a touch of reflection, a bit of rediscovery, and some “science-fiction” will be published in addition to the usual edition.",,"['Séroussi, B.', 'Jaulent, M.-C.', 'Lehmann, C. U.']",,,,
,PMC,Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection,http://dx.doi.org/10.1073/pnas.1510830112,PMC4507189,,,"Traditional approaches to antimicrobial drug development are poorly suited to combatting the emergence of novel pathogens. Additionally, the lack of small animal models for these infections hinders the in vivo testing of potential therapeutics. Here we demonstrate the use of the VelocImmune technology (a mouse that expresses human antibody-variable heavy chains and κ light chains) alongside the VelociGene technology (which allows for rapid engineering of the mouse genome) to quickly develop and evaluate antibodies against an emerging viral disease. Specifically, we show the rapid generation of fully human neutralizing antibodies against the recently emerged Middle East Respiratory Syndrome coronavirus (MERS-CoV) and development of a humanized mouse model for MERS-CoV infection, which was used to demonstrate the therapeutic efficacy of the isolated antibodies. The VelocImmune and VelociGene technologies are powerful platforms that can be used to rapidly respond to emerging epidemics.",,"['Pascal, Kristen E.', 'Coleman, Christopher M.', 'Mujica, Alejandro O.', 'Kamat, Vishal', 'Badithe, Ashok', 'Fairhurst, Jeanette', 'Hunt, Charleen', 'Strein, John', 'Berrebi, Alexander', 'Sisk, Jeanne M.', 'Matthews, Krystal L.', 'Babb, Robert', 'Chen, Gang', 'Lai, Ka-Man V.', 'Huang, Tammy T.', 'Olson, William', 'Yancopoulos, George D.', 'Stahl, Neil', 'Frieman, Matthew B.', 'Kyratsous, Christos A.']",,,,
,PMC,"Contact tracing the first Middle East respiratory syndrome case in the Philippines, February 2015",http://dx.doi.org/10.5365/WPSAR.2015.6.2.012,PMC4675163,,,"BACKGROUND: Middle East respiratory syndrome (MERS) is an illness caused by a coronavirus in which infected persons develop severe acute respiratory illness. A person can be infected through close contacts. This is an outbreak investigation report of the first confirmed MERS case in the Philippines and the subsequent contact tracing activities. METHODS: Review of patient records and interviews with health-care personnel were done. Patient and close contacts were tested for MERS-coronavirus (CoV) by real time-polymerase chain reaction. Close contacts were identified and categorized. All traced contacts were monitored daily for appearance of illness for 14 days starting from the date of last known exposure to the confirmed case. A standard log sheet was used for symptom monitoring. RESULTS: The case was a 31-year-old female who was a health-care worker in Saudi Arabia. She had mild acute respiratory illness five days before travelling to the Philippines. On 1 February, she travelled with her husband to the Philippines while she had a fever. On 2 February, she attended a health facility in the Philippines. On 8 February, respiratory samples were tested for MERS-CoV and yielded positive results. A total of 449 close contacts were identified, and 297 (66%) were traced. Of those traced, 15 developed respiratory symptoms. All of them tested negative for MERS. DISCUSSION: In this outbreak investigation, the participation of health-care personnel in conducting vigorous contact tracing may have reduced the risk of transmission. However, being overly cautious to include more contacts for the outbreak response should be further reconsidered.",,"['Racelis, Sheryl', 'de los Reyes, Vikki Carr', 'Sucaldito, Ma Nemia', 'Deveraturda, Imelda', 'Roca, John Bobbie', 'Tayag, Enrique']",,,,
,PMC,"Exchange protein directly activated by cAMP encoded by the mammalian rapgef3 gene: Structure, function and therapeutics",http://dx.doi.org/10.1016/j.gene.2015.06.063,PMC4556420,,,"Mammalian exchange protein directly activated by cAMP isoform 1 (EPAC1), encoded by the RAPGEF3 gene, is one of the two-membered family of cAMP sensors that mediate the intracellular functions of cAMP by acting as guanine nucleotide exchange factors for the Ras-like Rap small GTPases. Extensive studies have revealed that EPAC1-mediated cAMP signaling is highly coordinated spatiotemporally through the formation of dynamic signalosomes by interacting with a diverse array of cellular partners. Recent functional analyses of genetically engineered mouse models further suggest that EPAC1 functions as an important stress response switch and is involved in pathophysiological conditions of cardiac stresses, chronic pain, cancer and infectious diseases. These findings, coupled with the development of EPAC specific small molecule modulators, validate EPAC1 as a promising target for therapeutic interventions.",,"['Banerjee, Upasana', 'Cheng, Xiaodong']",,,,
,PMC,"Preliminary epidemiologic assessment of MERS-CoV outbreak in South Korea, May–June 2015",,PMC4535930,,,"South Korea is experiencing the largest outbreak of Middle East respiratory syndrome coronavirus infections outside the Arabian Peninsula, with 166 laboratory-confirmed cases, including 24 deaths as of 19 June 2015. We estimated that the mean incubation period was 6.7 days and the mean serial interval 12.6 days. We found it unlikely that infectiousness precedes symptom onset. Based on currently available data, we predict an overall case fatality risk of 21.3% (95% credible interval: 14%–31%).",,"['Cowling, Benjamin J', 'Park, Minah', 'Fang, Vicky J', 'Wu, Peng', 'Leung, Gabriel M', 'Wu, Joseph T']",,,,
,PMC,Paradoxes and wonders of intrinsic disorder: Prevalence of exceptionality,http://dx.doi.org/10.1080/21690707.2015.1065029,PMC5314900,,,,,"Uversky, Vladimir N",,,,
,PMC,Influence of human behavior on cholera dynamics,http://dx.doi.org/10.1016/j.mbs.2015.06.009,PMC4537851,,,"This paper is devoted to studying the impact of human behavior on cholera infection. We start with a cholera ordinary differential equation (ODE) model that incorporates human behavior via modeling disease prevalence dependent contact rates for direct and indirect transmissions and infectious host shedding. Local and global dynamics of the model are analyzed with respect to the basic reproduction number. We then extend the ODE model to a reaction-convection-diffusion partial differential equation (PDE) model that accounts for the movement of both human hosts and bacteria. Particularly, we investigate the cholera spreading speed by analyzing the traveling wave solutions of the PDE model, and disease threshold dynamics by numerically evaluating the basic reproduction number of the PDE model. Our results show that human behavior can reduce (a) the endemic and epidemic levels, (b) cholera spreading speeds and (c) the risk of infection (characterized by the basic reproduction number).",,"['Wang, Xueying', 'Gao, Daozhou', 'Wang, Jin']",,,,
,PMC,Serotonin Receptor Agonist 5-Nonyloxytryptamine Alters the Kinetics of Reovirus Cell Entry,http://dx.doi.org/10.1128/JVI.00739-15,PMC4524060,,,"Mammalian orthoreoviruses (reoviruses) are nonenveloped double-stranded RNA viruses that infect most mammalian species, including humans. Reovirus binds to cell surface glycans, junctional adhesion molecule A (JAM-A), and the Nogo-1 receptor (depending on the cell type) and enters cells by receptor-mediated endocytosis. Within the endocytic compartment, reovirus undergoes stepwise disassembly, which is followed by release of the transcriptionally active viral core into the cytoplasm. In a small-molecule screen to identify host mediators of reovirus infection, we found that treatment of cells with 5-nonyloxytryptamine (5-NT), a prototype serotonin receptor agonist, diminished reovirus cytotoxicity. 5-NT also blocked reovirus infection. In contrast, treatment of cells with methiothepin mesylate, a serotonin antagonist, enhanced infection by reovirus. 5-NT did not alter cell surface expression of JAM-A or attachment of reovirus to cells. However, 5-NT altered the distribution of early endosomes with a concomitant impairment of reovirus transit to late endosomes and a delay in reovirus disassembly. Consistent with an inhibition of viral disassembly, 5-NT treatment did not alter infection by in vitro-generated infectious subvirion particles, which bind to JAM-A but bypass a requirement for proteolytic uncoating in endosomes to infect cells. We also found that treatment of cells with 5-NT decreased the infectivity of alphavirus chikungunya virus and coronavirus mouse hepatitis virus. These data suggest that serotonin receptor signaling influences cellular activities that regulate entry of diverse virus families and provides a new, potentially broad-spectrum target for antiviral drug development. IMPORTANCE Identification of well-characterized small molecules that modulate viral infection can accelerate development of antiviral therapeutics while also providing new tools to increase our understanding of the cellular processes that underlie virus-mediated cell injury. We conducted a small-molecule screen to identify compounds capable of inhibiting cytotoxicity caused by reovirus, a prototype double-stranded RNA virus. We found that 5-nonyloxytryptamine (5-NT) impairs reovirus infection by altering viral transport during cell entry. Remarkably, 5-NT also inhibits infection by an alphavirus and a coronavirus. The antiviral properties of 5-NT suggest that serotonin receptor signaling is an important regulator of infection by diverse virus families and illuminate a potential new drug target.",,"['Mainou, Bernardo A.', 'Ashbrook, Alison W.', 'Smith, Everett Clinton', 'Dorset, Daniel C.', 'Denison, Mark R.', 'Dermody, Terence S.']",,,,
,PMC,Pharmacological approaches to intervention in hypomyelinating and demyelinating white matter pathology,http://dx.doi.org/10.1016/j.neuropharm.2015.06.008,PMC4690794,,,"White matter disease afflicts both developing and mature central nervous systems. Both cell intrinsic and extrinsic dysregulation result in profound changes in cell survival, axonal metabolism and functional performance. Experimental models of developmental white matter (WM) injury and demyelination have not only delineated mechanisms of signaling and inflammation, but have also paved the way for the discovery of pharmacological approaches to intervention. These reagents have been shown to enhance protection of the mature oligodendrocyte cell, accelerate progenitor cell recruitment and/or differentiation, or attenuate pathological stimuli arising from the inflammatory response to injury. Here we highlight reports of studies in the CNS in which compounds, namely peptides, hormones, and small molecule agonists/antagonists, have been used in experimental animal models of demyelination and neonatal brain injury that affect aspects of excitotoxicity, oligodendrocyte development and survival, and progenitor cell function, and which have been demonstrated to attenuate damage and improve WM protection in experimental models of injury. The molecular targets of these agents include growth factor and neurotransmitter receptors, morphogens and their signaling components, nuclear receptors, as well as the processes of iron transport and actin binding. By surveying the current evidence in non-immune targets of both the immature and mature WM, we aim to better understand pharmacological approaches modulating endogenous oligodendroglia that show potential for success in the contexts of developmental and adult WM pathology.",,"['Chew, Li-Jin', 'DeBoy, Cynthia A']",,,,
,PMC,"Effect of the Ebola-virus-disease epidemic on malaria case management in Guinea, 2014: a cross-sectional survey of health facilities",http://dx.doi.org/10.1016/S1473-3099(15)00061-4,PMC4669675,,,"BACKGROUND: The ongoing west Africa Ebola-virus-disease epidemic has disrupted the entire health-care system in affected countries. Because of the overlap of symptoms of Ebola virus disease and malaria, the care delivery of malaria is particularly sensitive to the indirect effects of the current Ebola-virus-disease epidemic. We therefore characterise malaria case management in the context of the Ebola-virus-disease epidemic and document the effect of the Ebola-virus-disease epidemic on malaria case management. METHODS: We did a cross-sectional survey of public health facilities in Guinea in December, 2014. We selected the four prefectures most affected by Ebola virus disease and selected four randomly from prefectures without any reported cases of the disease. 60 health facilities were sampled in Ebola-affected and 60 in Ebola-unaffected prefectures. Study teams abstracted malaria case management indicators from registers for January to November for 2013 and 2014 and interviewed health-care workers. Nationwide weekly surveillance data for suspect malaria cases reported between 2011 and 2014 were analysed independently. Data for malaria indicators in 2014 were compared with previous years. FINDINGS: We noted substantial reductions in all-cause outpatient visits (by 23 103 [11%] of 214 899), cases of fever (by 20249 [15%] of 131 330), and patients treated with oral (by 22 655 [24%] of 94 785) and injectable (by 5219 [30%] of 17 684) antimalarial drugs in surveyed health facilities. In Ebola-affected prefectures, 73 of 98 interviewed community health workers were operational (74%, 95% CI 65–83) and 35 of 73 were actively treating malaria cases (48%, 36–60) compared with 106 of 112 (95%, 89–98) and 102 of 106 (96%, 91–99), respectively, in Ebola-unaffected prefectures. Nationwide, the Ebola-virus-disease epidemic was estimated to have resulted in 74 000 (71 000–77 000) fewer malaria cases seen at health facilities in 2014. INTERPRETATION: The reduction in the delivery of malaria care because of the Ebola-virus-disease epidemic threatens malaria control in Guinea. Untreated and inappropriately treated malaria cases lead to excess malaria mortality and more fever cases in the community, impeding the Ebola-virus-disease response. FUNDING: Global Fund to Fight AIDS, Tuberculosis and Malaria, and President’s Malaria Initiative.",,"['Plucinski, Mateusz M', 'Guilavogui, Timothée', 'Sidikiba, Sidibe', 'Diakité, Nouman', 'Diakité, Souleymane', 'Dioubaté, Mohamed', 'Bah, Ibrahima', 'Hennessee, Ian', 'Butts, Jessica K', 'Halsey, Eric S', 'McElroy, Peter D', 'Kachur, S Patrick', 'Aboulhab, Jamila', 'James, Richard', 'Keita, Moussa']",,,,
,PMC,Cathepsin L suppression increases the radiosensitivity of human glioma U251 cells via G(2)/M cell cycle arrest and DNA damage,http://dx.doi.org/10.1038/aps.2015.36,PMC4561966,,,"AIM: Cathepsin L is a lysosomal cysteine protease that plays important roles in cancer tumorigenesis, proliferation and chemotherapy resistance. The aim of this study was to determine how cathepsin L regulated the radiosensitivity of human glioma cells in vitro. METHODS: Human glioma U251 cells (harboring the mutant type p53 gene) and U87 cells (harboring the wide type p53 gene) were irradiated with X-rays. The expression of cathepsin L was analyzed using Western blot and immunofluorescence assays. Cell survival and DNA damage were evaluated using clonogenic and comet assays, respectively. Flow cytometry was used to detect the cell cycle distribution. Apoptotic cells were observed using Hoechst 33258 staining and fluorescence microscopy. RESULTS: Irradiation significantly increased the cytoplasmic and nuclear levels of cathepsin L in U251 cells but not in U87 cells. Treatment with the specific cathepsin L inhibitor Z-FY-CHO (10 μmol/L) or transfection with cathepsin L shRNA significantly increased the radiosensitivity of U251 cells. Both suppression and knockdown of cathepsin L in U251 cells increased irradiation-induced DNA damage and G(2)/M phase cell cycle arrest. Both suppression and knockdown of cathepsin L in U251 cells also increased irradiation-induced apoptosis, as shown by the increased levels of Bax and decreased levels of Bcl-2. CONCLUSION: Cathepsin L is involved in modulation of radiosensitivity in human glioma U251 cells (harboring the mutant type p53 gene) in vitro.",,"['Zhang, Qing-qing', 'Wang, Wen-juan', 'Li, Jun', 'Yang, Neng', 'Chen, Gang', 'Wang, Zhong', 'Liang, Zhong-qin']",,,,
,PMC,Human neutralizing antibodies against MERS coronavirus: implications for future immunotherapy,http://dx.doi.org/10.2217/imt.15.33,PMC5068219,,,,,"['Tang, Xian-Chun', 'Marasco, Wayne A']",,,,
,PMC,Is the ferret a suitable species for studying perinatal brain injury?,http://dx.doi.org/10.1016/j.ijdevneu.2015.06.005,PMC4793918,,,"Complications of prematurity often disrupt normal brain development and/or cause direct damage to the developing brain, resulting in poor neurodevelopmental outcomes. Physiologically relevant animal models of perinatal brain injury can advance our understanding of these influences and thereby provide opportunities to develop therapies and improve long-term outcomes. While there are advantages to currently available small animal models, there are also significant drawbacks that have limited translation of research findings to humans. Large animal models such as newborn pig, sheep and nonhuman primates have complex brain development more similar to humans, but these animals are expensive, and developmental testing of sheep and piglets is limited. Ferrets (Mustela putorius furo) are born lissencephalic and undergo postnatal cortical folding to form complex gyrencephalic brains. This review examines whether ferrets might provide a novel intermediate animal model of neonatal brain disease that has the benefit of a gyrified, altricial brain in a small animal. It summarizes attributes of ferret brain growth and development that make it an appealing animal in which to model perinatal brain injury. We postulate that because of their innate characteristics, ferrets have great potential in neonatal neurodevelopmental studies.",,"['Empie, Kristen', 'Rangarajan, Vijayeta', 'Juul, Sandra E.']",,,,
,PMC,HIV-infected microglia mediate cathepsin B induced neurotoxicity,http://dx.doi.org/10.1007/s13365-015-0358-7,PMC4618197,,,"BACKGROUND: HIV-1-infected mononuclear phagocytes release soluble factors that affect the homeostasis in tissue. HIV-1 can prompt metabolic encephalopathy with the addition of neuronal dysfunction and apoptosis. Recently, we reported that HIV-1 enhances the expression and secretion of bioactive cathepsin B in monocyte-derived macrophages, ultimately contributing to neuronal apoptosis. In this research, we request if microglia respond to HIV infection similarly by modifying the expression, secretion, neurotoxic potential of cathepsin B and the in vivo relevance of these findings. METHODS: HIV-(ADA) infected human primary microglia and CHME-5 were assessed for expression and activity of cathepsin B, its inhibitors, cystatins B and C, and neurotoxicity associated with these changes. Human primary neurons were exposed to supernatants from HIV-infected and uninfected microglia in the presence of cathepsin B inhibitors and apoptosis was assessed by TUNEL. Microglial expression of cathepsin B was validated in brain tissue from HIVE patients. RESULTS: HIV-infected microglia secreted significantly greater levels of cathepsin B, cystatin B, and cystatin C compared to uninfected cells. Increased apoptosis was observed in neurons exposed to supernatants from HIV-1 infected microglia at days 12 post-infection. The cathepsin B inhibitor CA-074 and cathepsin B antibody prevented neuronal apoptosis. Increased microglia-derived cathepsin B, cystatin B, and cystatin C and caspase-3+ neurons were detected in HIVE brains compared to controls. CONCLUSIONS: Our results suggest that HIV-1-induced cathepsin B production in microglia contributes to neuronal apoptosis and may be an important factor in neuronal death associated with HIVE.",,"['Zenón, Frances', 'Cantres-Rosario, Yisel', 'Adiga, Radhika', 'Gonzalez, Mariangeline', 'Rodriguez-Franco, Eillen', 'Langford, Dianne', 'Melendez, Loyda M.']",,,,
,PMC,Targeting zoonotic viruses: structure-based inhibition of the 3C-like protease from bat coronavirus HKU4 – the likely reservoir host to the human coronavirus that causes Middle East Respiratory Syndrome (MERS),http://dx.doi.org/10.1016/j.bmc.2015.06.039,PMC5433438,,,"The bat coronavirus HKU4 belongs to the same 2c lineage as that of the deadly Middle East Respiratory Syndrome coronavirus (MERS-CoV) and shows high sequence similarity, therefore potentiating a threat to the human population through a zoonotic shift or “spill over” event. To date, there are no effective vaccines or antiviral treatments available that are capable of limiting the pathogenesis of any human coronaviral infection. An attractive target for the development of anti-coronaviral therapeutics is the 3C-like protease (3CL(pro)), which is essential for the progression of the coronaviral life cycle. Herein, we report the screening results of a small, 230-member peptidomimetic library against HKU4-CoV 3CL(pro) and the identification of 43 peptidomimetic compounds showing good to excellent inhibitory potency of HKU4-CoV 3CL(pro) with IC(50) values ranging from low micromolar to sub-micromolar. We established structure-activity relationships (SARs) describing the important ligand-based features required for potent HKU4-CoV 3CL(pro) inhibition and identified a seemingly favored peptidic backbone for HKU4-CoV 3CL(pro) inhibition. To investigate this, a molecular sub-structural analysis of the most potent HKU4-CoV 3CL(pro) inhibitor was accomplished by the synthesis and testing of the lead peptidomimetic inhibitor's sub-structural components, confirming the activity of the favored backbone (22A) identified via SAR analysis. In order to elucidate the structural reasons for such potent HKU4-CoV 3CL(pro) inhibition by the peptidomimetics having the 22A backbone, we determined the X-ray structures of HKU4-CoV 3CL(pro) in complex with three peptidomimetic inhibitors. Sequence alignment of HKU4-CoV 3CL(pro), and two other lineage C Betacoronaviruses 3CL(pro)'s, HKU5-CoV and MERS-CoV 3CL(pro), show that the active site residues of HKU4-CoV 3CL(pro) that participate in inhibitor binding are conserved in HKU5-CoV and MERS-CoV 3CL(pro). Furthermore, we assayed our most potent HKU4-CoV 3CL(pro) inhibitor for inhibition of HKU5-CoV 3CL(pro) and found it to have sub-micromolar inhibitory activity (IC(50) = 0.54 ± 0.03 μM). The X-ray structures and SAR analysis reveal critical insights into the structure and inhibition of HKU4-CoV 3CL(pro), providing fundamental knowledge that may be exploited in the development of anti-coronaviral therapeutics for coronaviruses emerging from zoonotic reservoirs.",,"['St. John, Sarah E.', 'Tomar, Sakshi', 'Stauffer, Shaun R.', 'Mesecar, Andrew D.']",,,,
,PMC,Age-associated Failure to Adjust Type I Interferon Receptor Signaling Thresholds after T-cell Activation(),http://dx.doi.org/10.4049/jimmunol.1402389,PMC4506866,,,"With increasing age, naïve CD4 T cells acquire intrinsic defects that compromise their ability to respond and differentiate. Type I IFNs, pervasive constituents of the environment in which adaptive immune responses occur, are known to regulate T cell differentiation and survival. Activated naïve CD4 T cells from older individuals have reduced responses to type I IFN, a defect that develops during activation and is not observed in quiescent naïve CD4 T cells. Naïve CD4 T cells from young adults upregulate the expression of STAT1 and STAT5 after activation, lowering their threshold to respond to type I IFN stimulation. The heightened STAT signaling is critical to maintain the expression of CD69 that regulates lymphocyte egress and the ability to produce IL-2 and to survive. Although activation of T cells from older adults also induces transcription of STAT1 and STAT5, failure to exclude SHP1 to the signaling complex blunts their type I IFN response. In summary, our data show that type I IFN signaling thresholds in naïve CD4 T cells after activation are dynamically regulated to respond environmental cues for clonal expansion and memory cell differentiation. Naïve CD4 T cells from older adults have a defect in this threshold calibration. Restoring their ability to respond to type I IFN emerges as a promising target to restore T cell responses and improve the induction of T cell memory.",,"['Li, Guangjin', 'Ju, Jihang', 'Weyand, Cornelia M.', 'Goronzy, Jörg J.']",,,,
,PMC,Blood Groups in Infection and Host Susceptibility,http://dx.doi.org/10.1128/CMR.00109-14,PMC4475644,,,"Blood group antigens represent polymorphic traits inherited among individuals and populations. At present, there are 34 recognized human blood groups and hundreds of individual blood group antigens and alleles. Differences in blood group antigen expression can increase or decrease host susceptibility to many infections. Blood groups can play a direct role in infection by serving as receptors and/or coreceptors for microorganisms, parasites, and viruses. In addition, many blood group antigens facilitate intracellular uptake, signal transduction, or adhesion through the organization of membrane microdomains. Several blood groups can modify the innate immune response to infection. Several distinct phenotypes associated with increased host resistance to malaria are overrepresented in populations living in areas where malaria is endemic, as a result of evolutionary pressures. Microorganisms can also stimulate antibodies against blood group antigens, including ABO, T, and Kell. Finally, there is a symbiotic relationship between blood group expression and maturation of the gastrointestinal microbiome.",,"Cooling, Laura",,,,
,PMC,Respiratory Infections in the U.S. Military: Recent Experience and Control,http://dx.doi.org/10.1128/CMR.00039-14,PMC4475643,,,"This comprehensive review outlines the impact of military-relevant respiratory infections, with special attention to recruit training environments, influenza pandemics in 1918 to 1919 and 2009 to 2010, and peacetime operations and conflicts in the past 25 years. Outbreaks and epidemiologic investigations of viral and bacterial infections among high-risk groups are presented, including (i) experience by recruits at training centers, (ii) impact on advanced trainees in special settings, (iii) morbidity sustained by shipboard personnel at sea, and (iv) experience of deployed personnel. Utilizing a pathogen-by-pathogen approach, we examine (i) epidemiology, (ii) impact in terms of morbidity and operational readiness, (iii) clinical presentation and outbreak potential, (iv) diagnostic modalities, (v) treatment approaches, and (vi) vaccine and other control measures. We also outline military-specific initiatives in (i) surveillance, (ii) vaccine development and policy, (iii) novel influenza and coronavirus diagnostic test development and surveillance methods, (iv) influenza virus transmission and severity prediction modeling efforts, and (v) evaluation and implementation of nonvaccine, nonpharmacologic interventions.",,"['Sanchez, Jose L.', 'Cooper, Michael J.', 'Myers, Christopher A.', 'Cummings, James F.', 'Vest, Kelly G.', 'Russell, Kevin L.', 'Sanchez, Joyce L.', 'Hiser, Michelle J.', 'Gaydos, Charlotte A.']",,,,
,PMC,Urgent development of effective therapeutic and prophylactic agents to control the emerging threat of Middle East respiratory syndrome (MERS),http://dx.doi.org/10.1038/emi.2015.37,PMC4773045,26954884,CC BY,,2015 Jun 17,"['Lu, Lu', 'Xia, Shuai', 'Ying, Tianlei', 'Jiang, Shibo']",Emerg Microbes Infect,,,
,PMC,The Nucleocapsid Protein of Coronaviruses Acts as a Viral Suppressor of RNA Silencing in Mammalian Cells,http://dx.doi.org/10.1128/JVI.01331-15,PMC4524063,,,"RNA interference (RNAi) is a process of eukaryotic posttranscriptional gene silencing that functions in antiviral immunity in plants, nematodes, and insects. However, recent studies provided strong supports that RNAi also plays a role in antiviral mechanism in mammalian cells. To combat RNAi-mediated antiviral responses, many viruses encode viral suppressors of RNA silencing (VSR) to facilitate their replication. VSRs have been widely studied for plant and insect viruses, but only a few have been defined for mammalian viruses currently. We identified a novel VSR from coronaviruses, a group of medically important mammalian viruses including Severe acute respiratory syndrome coronavirus (SARS-CoV), and showed that the nucleocapsid protein (N protein) of coronaviruses suppresses RNAi triggered by either short hairpin RNAs or small interfering RNAs in mammalian cells. Mouse hepatitis virus (MHV) is closely related to SARS-CoV in the family Coronaviridae and was used as a coronavirus replication model. The replication of MHV increased when the N proteins were expressed in trans, while knockdown of Dicer1 or Ago2 transcripts facilitated the MHV replication in mammalian cells. These results support the hypothesis that RNAi is a part of the antiviral immunity responses in mammalian cells. IMPORTANCE RNAi has been well known to play important antiviral roles from plants to invertebrates. However, recent studies provided strong supports that RNAi is also involved in antiviral response in mammalian cells. An important indication for RNAi-mediated antiviral activity in mammals is the fact that a number of mammalian viruses encode potent suppressors of RNA silencing. Our results demonstrate that coronavirus N protein could function as a VSR through its double-stranded RNA binding activity. Mutational analysis of N protein allowed us to find out the critical residues for the VSR activity. Using the MHV-A59 as the coronavirus replication model, we showed that ectopic expression of SARS-CoV N protein could promote MHV replication in RNAi-active cells but not in RNAi-depleted cells. These results indicate that coronaviruses encode a VSR that functions in the replication cycle and provide further evidence to support that RNAi-mediated antiviral response exists in mammalian cells.",,"['Cui, Lei', 'Wang, Haiying', 'Ji, Yanxi', 'Yang, Jie', 'Xu, Shan', 'Huang, Xingyu', 'Wang, Zidao', 'Qin, Lei', 'Tien, Po', 'Zhou, Xi', 'Guo, Deyin', 'Chen, Yu']",,,,
,PMC,Identification of the Receptor-Binding Domain of the Spike Glycoprotein of Human Betacoronavirus HKU1,http://dx.doi.org/10.1128/JVI.03737-14,PMC4524053,,,"Coronavirus spike (S) glycoproteins mediate receptor binding, membrane fusion, and virus entry and determine host range. Murine betacoronavirus (β-CoV) in group A uses the N-terminal domain (NTD) of S protein to bind to its receptor, whereas the β-CoVs severe acute respiratory syndrome CoV in group B and Middle East respiratory syndrome CoV in group C and several α-CoVs use the downstream C domain in their S proteins to recognize their receptor proteins. To identify the receptor-binding domain in the spike of human β-CoV HKU1 in group A, we generated and mapped a panel of monoclonal antibodies (MAbs) to the ectodomain of HKU1 spike protein. They did not cross-react with S proteins of any other CoV tested. Most of the HKU1 spike MAbs recognized epitopes in the C domain between amino acids 535 and 673, indicating that this region is immunodominant. Two of the MAbs blocked HKU1 virus infection of primary human tracheal-bronchial epithelial (HTBE) cells. Preincubation of HTBE cells with a truncated HKU1 S protein that includes the C domain blocked infection with HKU1 virus, but preincubation of cells with truncated S protein containing only the NTD did not block infection. These data suggest that the receptor-binding domain (RBD) of HKU1 spike protein is located in the C domain, where the spike proteins of α-CoVs and β-CoVs in groups B and C bind to their specific receptor proteins. Thus, two β-CoVs in group A, HKU1 and murine CoV, have evolved to use different regions of their spike glycoproteins to recognize their respective receptor proteins. IMPORTANCE Mouse hepatitis virus, a β-CoV in group A, uses the galectin-like NTD in its spike protein to bind its receptor protein, while HCoV-OC43, another β-CoV in group A, uses the NTD to bind to its sialic-acid containing receptor. In marked contrast, the NTD of the spike glycoprotein of human respiratory β-CoV HKU1, which is also in group A, does not bind sugar. In this study, we showed that for the spike protein of HKU1, the purified C domain, downstream of the NTD, could block HKU1 virus infection of human respiratory epithelial cells, and that several monoclonal antibodies that mapped to the C domain neutralized virus infectivity. Thus, the receptor-binding domain of HKU1 spike glycoprotein is located in the C domain. Surprisingly, two β-CoVs in group A, mouse hepatitis virus and HKU1, have evolved to use different regions of their spike glycoproteins to recognize their respective receptors.",,"['Qian, Zhaohui', 'Ou, Xiuyuan', 'Góes, Luiz Gustavo Bentim', 'Osborne, Christina', 'Castano, Anna', 'Holmes, Kathryn V.', 'Dominguez, Samuel R.']",,,,
,PMC,Targeting Importin-α7 as a Therapeutic Approach against Pandemic Influenza Viruses,http://dx.doi.org/10.1128/JVI.00583-15,PMC4524051,,,"Viral drug resistance is believed to be less likely to occur if compounds are directed against cellular rather than viral proteins. In this study, we analyzed the feasibility of a crucial viral replication factor, namely, importin-α7, as a cellular drug target to combat pandemic influenza viruses. Surprisingly, only five viral lung-to-lung passages were required to achieve 100% lethality in importin-α7(−/−) mice that otherwise are resistant. Viral escape from importin-α7 requirement was mediated by five mutations in the viral ribonucleoprotein complex and the surface glycoproteins. Moreover, the importin-α7(−/−) mouse-adapted strain became even more virulent for wild-type mice than the parental strain. These studies show that targeting host proteins may still result in viral escape by alternative pathways, eventually giving rise to even more virulent virus strains. Thus, therapeutic intervention strategies should consider a multitarget approach to reduce viral drug resistance. IMPORTANCE Here, we investigated the long-standing hypothesis based on in vitro studies that viral drug resistance occurrence is less likely if compounds are directed against cellular rather than viral proteins. Here, we challenged this hypothesis by analyzing, in an in vivo animal model, the feasibility of targeting the cellular factor importin-α7, which is crucial for human influenza virus replication and pathogenesis, as an efficient antiviral strategy against pandemic influenza viruses. In summary, our studies suggest that resistance against cellular factors is possible in vivo, and the emergence of even more virulent viral escape variants calls for particular caution. Thus, therapeutic intervention strategies should consider a multitarget approach using compounds against viral as well as cellular factors to reduce the risk of viral drug resistance and potentially increased virulence.",,"['Resa-Infante, Patricia', 'Paterson, Duncan', 'Bonet, Jaume', 'Otte, Anna', 'Oliva, Baldo', 'Fodor, Ervin', 'Gabriel, Gülsah']",,,,
,PMC,From genome-scale data to models of infectious disease: a Bayesian network-based strategy to drive model development,http://dx.doi.org/10.1016/j.mbs.2015.06.006,PMC4679518,,,"High-throughput, genome-scale data present a unique opportunity to link host to pathogen on a molecular level. Forging such connections will help drive the development of mathematical models to better understand and predict both pathogen behavior and the epidemiology of infectious diseases, including malaria. However, the datasets that can aid in identifying these links and models are vast and not amenable to simple, reductionist, and univariate analyses. These datasets require data mining in order to identify the truly important measurements that best describe clinical and molecular observations. Moreover, these datasets typically have relatively few samples due to experimental limitations (particularly for human studies or in vivo animal experiments), making data mining extremely difficult. Here, after first providing a brief overview of common strategies for data reduction and identification of relationships between variables for inclusion in mathematical models, we present a new generalized strategy for performing these data reduction and relationship inference tasks. Our approach emphasizes the importance of robustness when using data to drive model development, particularly when using genome-scale, small-sample in vivo data. We identify the use of appropriate feature reduction combined with data permutations and subsampling strategies as being critical to enable increasingly robust results from network inference using high-dimensional, low-observation data.",,"['Yin, Weiwei', 'Kissinger, Jessica C.', 'Moreno, Alberto', 'Galinski, Mary R.', 'Styczynski, Mark P.']",,,,
,PMC,Middle East respiratory syndrome,http://dx.doi.org/10.1503/cmaj.140951,PMC4467933,,,,,"['Al-Maani, Amal', 'Gold, Wayne L.', 'McGeer, Allison']",,,,
,PMC,Highlights,,PMC4467920,,,,,,,,,
,PMC,Deubiquitinases (DUBs) and DUB inhibitors: a patent review,http://dx.doi.org/10.1517/13543776.2015.1056737,PMC4834700,,,"INTRODUCTION: Deubiquitinating-enzymes (DUBs) are key components of the ubiquitin-proteasome-system (UPS). The fundamental role of DUBs is specific removal of ubiquitin from substrates. DUBs contribute to activation/deactivation, recycling and localization of numerous regulatory-proteins, thus playing major roles in diverse cellular-processes. Altered DUB activity is associated with multitudes of pathologies including cancer. Therefore, DUBs represent novel candidates for target-directed drug development. AREAS COVERED: The article is a thorough review/accounting of patented compounds targeting DUBs stratifying/classifying the patented compounds based on: chemical-structures, nucleic-acid compositions, modes-of-action and targeting-sites. The review provides a brief background on the UPS and DUBs involvement. Furthermore, methods for assessing efficacy and potential pharmacological utility of DUB inhibitor (DUBi) are discussed. EXPERT OPINION: The FDA’s approval of the 20S proteasome inhibitors: bortezomib and carfilzomib for treatment of hematological malignancies established the UPS as an anti-cancer target. Unfortunately, many patients are inherently resistant or develop resistance to proteasome inhibitors (PIs). One potential strategy to combat PI resistance is targeting upstream components of the UPS such as DUBs. DUBs represent a promising potential therapeutic target due to their critical roles in various cellular processes including protein-turnover, localization and cellular homeostasis. While considerable efforts have been undertaken to develop DUB modulators, significant advancement is necessary move DUB inhibitors into the clinic.",,"['Farshi, Pershang', 'Deshmukh, Rahul R.', 'Nwankwo, Joseph O.', 'Arkwright, Richard T.', 'Cvek, Boris', 'Liu, Jinbao', 'Dou, Q. Ping']",,,,
,PMC,Electrostatic Architecture of the Infectious Salmon Anemia Virus (ISAV) Core Fusion Protein Illustrates a Carboxyl-Carboxylate pH Sensor,http://dx.doi.org/10.1074/jbc.M115.644781,PMC4513110,,,"Segment 5, ORF 1 of the infectious salmon anemia virus (ISAV) genome, encodes for the ISAV F protein, which is responsible for viral-host endosomal membrane fusion during a productive ISAV infection. The entry machinery of ISAV is composed of a complex of the ISAV F and ISAV hemagglutinin esterase (HE) proteins in an unknown stoichiometry prior to receptor engagement by ISAV HE. Following binding of the receptor to ISAV HE, dissociation of the ISAV F protein from HE, and subsequent endocytosis, the ISAV F protein resolves into a fusion-competent oligomeric state. Here, we present a 2.1 Å crystal structure of the fusion core of the ISAV F protein determined at low pH. This structure has allowed us to unambiguously demonstrate that the ISAV entry machinery exhibits typical class I viral fusion protein architecture. Furthermore, we have determined stabilizing factors that accommodate the pH-dependent mode of ISAV transmission, and our structure has allowed the identification of a central coil that is conserved across numerous and varied post-fusion viral glycoprotein structures. We then discuss a mechanistic model of ISAV fusion that parallels the paramyxoviral class I fusion strategy wherein attachment and fusion are relegated to separate proteins in a similar fashion to ISAV fusion.",,"['Cook, Jonathan D.', 'Soto-Montoya, Hazel', 'Korpela, Markus K.', 'Lee, Jeffrey E.']",,,,
,PMC,Inhibition of Hepatitis E Virus Replication by Peptide-Conjugated Morpholino Oligomers,http://dx.doi.org/10.1016/j.antiviral.2015.06.006,PMC4502978,,,"Hepatitis E virus (HEV) infection is a cause of hepatitis in humans worldwide and has been associated with a mortality rate of up to 30% in pregnant women. Recently, persistent and chronic HEV infections have been recognized as a serious clinical problem, especially in immunocompromised individuals. To date, there are no FDA-approved HEV-specific antiviral drugs. In this study, we evaluated antisense peptide-conjugated morpholino oligomers (PPMO) designed against HEV genomic sequences as potential HEV-specific antiviral compounds. Two genetically-distinct strains of human HEV, genotype 1 Sar55 and genotype 3 Kernow-C1, isolated from patients with acute and chronic hepatitis, respectively, were used to evaluate inhibition of viral replication by PPMO in liver cells. The anti-HEV PPMO produced a significant reduction in the levels of HEV RNA and capsid protein, indicating effective inhibition of HEV replication. PPMO HP1, which targets a highly conserved sequence in the start site region of ORF1, was also effective against the genotype 3 Kernow-C1 strain in stably-infected HepG2/C3A liver cells. The antiviral activity observed was specific, dose-responsive and potent, suggesting that further exploration of PPMO HP1 as a potential HEV-specific antiviral agent is warranted.",,"['Nan, Yuchen', 'Ma, Zexu', 'Kannan, Harilakshmi', 'Stein, David A.', 'Iversen, Patrick I.', 'Meng, Xiang-Jin', 'Zhang, Yan-Jin']",,,,
,PMC,Effects of the fusion design and immunization route on the immunogenicity of Ag85A-Mtb32 in adenoviral vectored tuberculosis vaccine,http://dx.doi.org/10.1080/21645515.2015.1042193,PMC4514253,,,"Vaccines containing multiple antigens may induce broader immune responses and provide better protection against Mycobacterium tuberculosis (Mtb) infection as compared to a single antigen. However, strategies for incorporating multiple antigens into a single vector and the immunization routes may affect their immunogenicity. In this study, we utilized recombinant adenovirus type 5 (rAd5) as a model vaccine vector, and Ag85A (Rv3804c) and Mtb32 (Rv0125) as model antigens, to comparatively evaluate the influence of codon usage optimization, signal sequence, fusion linkers, and immunization routes on the immunogenicity of tuberculosis (TB) vaccine containing multiple antigens in C57BL/6 mice. We showed that codon-optimized Ag85A and Mtb32 fused with a GSG linker induced the strongest systemic and pulmonary cell-mediated immune (CMI) responses. Strong CMI responses were characterized by the generation of a robust IFN-γ ELISPOT response as well as antigen-specific CD4(+) T and CD8(+) T cells, which secreted mono-, dual-, or multiple cytokines. We also found that subcutaneous (SC) and intranasal (IN)/oral immunization with this candidate vaccine exhibited the strongest boosting effects for Mycobacterium bovis bacille Calmette-Guérin (BCG)-primed systemic and pulmonary CMI responses, respectively. Our results supported that codon optimized Ag85A and Mtb32 fused with a proper linker and immunized through SC and IN/oral routes can generate the strongest systemic and pulmonary CMI responses in BCG-primed mice, which may be particularly important for the design of TB vaccines containing multiple antigens.",,"['Zhang, Yiling', 'Feng, Liqiang', 'Li, Liang', 'Wang, Dimin', 'Li, Chufang', 'Sun, Caijun', 'Li, Pingchao', 'Zheng, Xuehua', 'Liu, Yichu', 'Yang, Wei', 'Niu, Xuefeng', 'Zhong, Nanshan', 'Chen, Ling']",,,,
,PMC,Hospital Transfer Network Structure as a Risk Factor for Clostridium difficile Infection,http://dx.doi.org/10.1017/ice.2015.130,PMC4736722,,,"OBJECTIVE: To determine the effect on inter-hospital patient sharing via transfers on the rate of Clostridium difficile infections (CDI) in a hospital. DESIGN: Retrospective cohort METHODS: Using data from the Healthcare Cost and Utilization Project California State Inpatient Database, 2005–2011, we identified 2,752,639 transfers. We then constructed a series of networks detailing the connections formed by hospitals. We computed two measures of connectivity, indegree and weighted indegree, measuring the number of hospitals from which transfers into a hospital arrive, and the total number of incoming transfers, respectively. We estimated a multivariate model of CDI cases using the log-transformed network measures as well as covariates for hospital fixed effects, log median length of stay, log fraction of patients aged 65 or older, quarter and year indicators as predictors. RESULTS: We found an increase of one in the log indegree was associated with a 4.8% increase in incidence of CDI (95% CI: 2.3–7.4) and an increase of one in log weighted indegree was associated with a 3.3% increase in CDI incidence (95% CI: 1.5–5.2). Moreover, including measures of connectivity in the models greatly improved their fit. CONCLUSIONS: Our results suggest infection control is not under the exclusive control of a given hospital but is also influenced by the connections and number of connections that hospitals have with other hospitals.",,"['Simmering, Jacob E.', 'Polgreen, Linnea A.', 'Campbell, David R.', 'Cavanaugh, Joseph E.', 'Polgreen, Philip M.']",,,,
,PMC,Broad-spectrum antivirals against viral fusion,http://dx.doi.org/10.1038/nrmicro3475,PMC4554337,,,"Effective antivirals have been developed against specific viruses, such as HIV, Hepatitis C virus and influenza virus. This ‘one bug–one drug’ approach to antiviral drug development can be successful, but it may be inadequate for responding to an increasing diversity of viruses that cause significant diseases in humans. The majority of viral pathogens that cause emerging and re-emerging infectious diseases are membrane-enveloped viruses, which require the fusion of viral and cell membranes for virus entry. Therefore, antivirals that target the membrane fusion process represent new paradigms for broad-spectrum antiviral discovery. In this Review, we discuss the mechanisms responsible for the fusion between virus and cell membranes and explore how broad-spectrum antivirals target this process to prevent virus entry.",,"['Vigant, Frederic', 'Santos, Nuno C.', 'Lee, Benhur']",,,,
,PMC,Harnessing nanoparticles for immune modulation,http://dx.doi.org/10.1016/j.it.2015.05.007,PMC4603374,,,"Recent approaches using nanoparticles engineered for immune regulation have yielded promising results in preclinical models of disease. The number of nanoparticle therapies is growing, fueled by innovations in nanotechnology and advances in understanding of the underlying pathogenesis of immune-mediated diseases. In particular, recent mechanistic insight into the ways in which nanoparticles interact with the mononuclear phagocyte system and impact its function during homeostasis and inflammation have highlighted the potential of nanoparticle-based therapies for controlling severe inflammation while concurrently restoring peripheral immune tolerance in autoimmune disease. Here we review recent advances in nanoparticle-based approaches aimed at immune-modulation, and discuss these in the context of concepts in polymeric nanoparticle development, including particle modification, delivery and the factors associated with successful clinical deployment.",,"['Getts, Daniel R.', 'Shea, Lonnie D', 'Miller, Stephen D.', 'King, Nicholas J.C.']",,,,
,PMC,Therapeutic Targets for the Treatment of Hepatitis E Virus Infection,http://dx.doi.org/10.1517/14728222.2015.1056155,PMC4834873,,,"INTRODUCTION: Hepatitis E virus (HEV) is one of the most common causes of acute viral hepatitis in the world with an estimated 20 million infections per year. Although the mortality rate is less than 1% among the general population, pregnant women can have a fatality rate of up to 30%. Additionally, chronic hepatitis E has increasingly become a significant clinical problem in immunocompromised individuals. Effective antivirals against HEV are needed. AREAS COVERED: This review article addresses the current state of knowledge of HEV infections with regard to animal and cell culture model systems that are important for antiviral discovery and testing, our current understanding of the molecular mechanisms of virus replication, our understanding of how each viral protein functions, and areas that can potentially be exploited as therapeutic targets. EXPERT OPINION: Lack of an efficient cell culture system for HEV propagation, the limited knowledge of HEV lifecycle, and the inherent self-limiting infection within the normal populace make the development of new therapeutic agents against HEV challenging. There are many promising therapeutic targets, and the tools for identifying and testing potential antivirals are rapidly evolving. The development of effective therapeutics against HEV in immunocompromised and pregnant patient populations is warranted.",,"['Kenney, Scott P.', 'Meng, Xiang-Jin']",,,,
,PMC,Cross-Protection of Influenza A Virus Infection by a DNA Aptamer Targeting the PA Endonuclease Domain,http://dx.doi.org/10.1128/AAC.00306-15,PMC4468670,,,"Amino acid residues in the N-terminal of the PA subunit (PA(N)) of the influenza A virus polymerase play critical roles in endonuclease activity, protein stability, and viral RNA (vRNA) promoter binding. In addition, PA(N) is highly conserved among different subtypes of influenza virus, which suggests PA(N) to be a desired target in the development of anti-influenza agents. We selected DNA aptamers targeting the intact PA protein or the PA(N) domain of an H5N1 virus strain using systematic evolution of ligands by exponential enrichment (SELEX). The binding affinities of selected aptamers were measured, followed by an evaluation of in vitro endonuclease inhibitory activity. Next, the antiviral effects of enriched aptamers against influenza A virus infections were examined. A total of three aptamers targeting PA and six aptamers targeting PA(N) were selected. Our data demonstrated that all three PA-selected aptamers neither inhibited endonuclease activity nor exhibited antiviral efficacy, whereas four of the six PA(N)-selected aptamers inhibited both endonuclease activity and H5N1 virus infection. Among the four effective aptamers, one exhibited cross-protection against infections of H1N1, H5N1, H7N7, and H7N9 influenza viruses, with a 50% inhibitory concentration (IC(50)) of around 10 nM. Notably, this aptamer was identified at the 5th round but disappeared after the 10th round of selection, suggesting that the identification and evaluation of aptamers at early rounds of selection may be highly helpful for screening effective aptamers. Overall, our study provides novel insights for screening and developing effective aptamers for use as anti-influenza drugs.",,"['Yuan, Shuofeng', 'Zhang, Naru', 'Singh, Kailash', 'Shuai, Huiping', 'Chu, Hin', 'Zhou, Jie', 'Chow, Billy K. C.', 'Zheng, Bo-Jian']",,,,
,PMC,Idiopathic pneumonia syndrome after hematopoietic cell transplantation: evidence of occult infectious etiologies,http://dx.doi.org/10.1182/blood-2014-12-617035,PMC4463739,,,"Newer diagnostic methods may link more idiopathic pneumonia syndrome (IPS) cases to an infectious agent. Bronchoalveolar lavage (BAL) samples from 69 hematopoietic cell transplant (HCT) recipients with IPS diagnosed between 1992 and 2006 were tested for 28 pathogens (3 bacteria and 25 viruses) by quantitative polymerase chain reaction and for Aspergillus by galactomannan assay. Research BALs from 21 asymptomatic HCT patients served as controls. Among 69 HCT patients with IPS, 39 (56.5%) had a pathogen detected. The most frequent pathogens were human herpesvirus-6 (HHV-6) (N = 20 [29%]) followed by human rhinovirus (HRV), cytomegalovirus (CMV), and Aspergillus (N = 8 [12%] in each). HHV-6 and HRV were rarely detected in controls, whereas CMV and Aspergillus were occasionally detected with low pathogen load. Patients with pathogens had worse day-100 survival than those without (hazard ratio, 1.88; P = .03). Mortality in patients with only pathogens of “uncertain” significance in lung was similar to that in patients with pathogens of “established” significance. Metagenomic next-generation sequencing did not reveal additional significant pathogens. Our study demonstrated that approximately half of patients with IPS had pathogens detected in BAL, and pathogen detection was associated with increased mortality. Thus, an expanded infection detection panel can significantly increase the diagnostic precision for idiopathic pneumonia.",,"['Seo, Sachiko', 'Renaud, Christian', 'Kuypers, Jane M.', 'Chiu, Charles Y.', 'Huang, Meei-Li', 'Samayoa, Erik', 'Xie, Hu', 'Yu, Guixia', 'Fisher, Cynthia E.', 'Gooley, Ted A.', 'Miller, Steven', 'Hackman, Robert C.', 'Myerson, David', 'Sedlak, Ruth H.', 'Kim, Yae-Jean', 'Fukuda, Takahiro', 'Fredricks, David N.', 'Madtes, David K.', 'Jerome, Keith R.', 'Boeckh, Michael']",,,,
,PMC,"Beclin orthologs: integrative hubs of cell signaling, membrane trafficking, and physiology",http://dx.doi.org/10.1016/j.tcb.2015.05.004,PMC4554927,,,"The Beclin family, including yeast Atg6 (autophagy related gene 6), its orthologs in higher eukaryotic species, and the more recently characterized mammalian-specific Beclin 2, are essential molecules in autophagy and other membrane-trafficking events. Extensive studies of Beclin orthologs have provided considerable insights into the regulation of autophagy, the diverse roles of autophagy in physiology and disease, and potential new strategies to modulate autophagy in a variety of clinical diseases. In this review we discuss the functions of Beclin 1 orthologs, the regulation of such functions by diverse cellular signaling pathways, and the effects of such regulation on downstream cellular processes including tumor suppression and metabolism. These findings suggest that Beclin orthologs serve as crucial molecules that integrate diverse environmental signals with membrane trafficking events to ensure optimal responses of the cell to stressful stimuli.",,"['Levine, Beth', 'Liu, Rong', 'Dong, Xiaonan', 'Zhong, Qing']",,,,
,PMC,"New technologies in predicting, preventing and controlling emerging infectious diseases",http://dx.doi.org/10.1080/21505594.2015.1040975,PMC4720248,,,"Surveillance of emerging infectious diseases is vital for the early identification of public health threats. Emergence of novel infections is linked to human factors such as population density, travel and trade and ecological factors like climate change and agricultural practices. A wealth of new technologies is becoming increasingly available for the rapid molecular identification of pathogens but also for the more accurate monitoring of infectious disease activity. Web-based surveillance tools and epidemic intelligence methods, used by all major public health institutions, are intended to facilitate risk assessment and timely outbreak detection. In this review, we present new methods for regional and global infectious disease surveillance and advances in epidemic modeling aimed to predict and prevent future infectious diseases threats.",,"Christaki, Eirini",,,,
,PMC,SIRT1 Suppresses Human T-Cell Leukemia Virus Type 1 Transcription,http://dx.doi.org/10.1128/JVI.01229-15,PMC4524255,,,"Human T-cell leukemia virus type 1 (HTLV-1)-associated diseases are poorly treatable, and HTLV-1 vaccines are not available. High proviral load is one major risk factor for disease development. HTLV-1 encodes Tax oncoprotein, which activates transcription from viral long terminal repeats (LTR) and various types of cellular promoters. Counteracting Tax function might have prophylactic and therapeutic benefits. In this work, we report on the suppression of Tax activation of HTLV-1 LTR by SIRT1 deacetylase. The transcriptional activity of Tax on the LTR was largely ablated when SIRT1 was overexpressed, but Tax activation of NF-κB was unaffected. On the contrary, the activation of the LTR by Tax was boosted when SIRT1 was depleted. Treatment of cells with resveratrol shunted Tax activity in a SIRT1-dependent manner. The activation of SIRT1 in HTLV-1-transformed T cells by resveratrol potently inhibited HTLV-1 proviral transcription and Tax expression, whereas compromising SIRT1 by specific inhibitors augmented HTLV-1 mRNA expression. The administration of resveratrol also decreased the production of cell-free HTLV-1 virions from MT2 cells and the transmission of HTLV-1 from MT2 cells to uninfected Jurkat cells in coculture. SIRT1 associated with Tax in HTLV-1-transformed T cells. Treatment with resveratrol prevented the interaction of Tax with CREB and the recruitment of CREB, CRTC1, and p300 to Tax-responsive elements in the LTR. Our work demonstrates the negative regulatory function of SIRT1 in Tax activation of HTLV-1 transcription. Small-molecule activators of SIRT1 such as resveratrol might be considered new prophylactic and therapeutic agents in HTLV-1-associated diseases. IMPORTANCE Human T-cell leukemia virus type 1 (HTLV-1) causes a highly lethal blood cancer or a chronic debilitating disease of the spinal cord. Treatments are unsatisfactory, and vaccines are not available. Disease progression is associated with robust expression of HTLV-1 genes. Suppressing HTLV-1 gene expression might have preventive and therapeutic benefits. It is therefore critical that host factors controlling HTLV-1 gene expression be identified and characterized. This work reveals a new host factor that suppresses HTLV-1 gene expression and a natural compound that activates this suppression. Our findings not only provide new knowledge of the host control of HTLV-1 gene expression but also suggest a new strategy of using natural compounds for prevention and treatment of HTLV-1-associated diseases.",,"['Tang, Hei-Man Vincent', 'Gao, Wei-Wei', 'Chan, Chi-Ping', 'Cheng, Yun', 'Deng, Jian-Jun', 'Yuen, Kit-San', 'Iha, Hidekatsu', 'Jin, Dong-Yan']",,,,
,PMC,Novel Receptor Specificity of Avian Gammacoronaviruses That Cause Enteritis,http://dx.doi.org/10.1128/JVI.00745-15,PMC4524090,,,"Viruses exploit molecules on the target membrane as receptors for attachment and entry into host cells. Thus, receptor expression patterns can define viral tissue tropism and might to some extent predict the susceptibility of a host to a particular virus. Previously, others and we have shown that respiratory pathogens of the genus Gammacoronavirus, including chicken infectious bronchitis virus (IBV), require specific α2,3-linked sialylated glycans for attachment and entry. Here, we studied determinants of binding of enterotropic avian gammacoronaviruses, including turkey coronavirus (TCoV), guineafowl coronavirus (GfCoV), and quail coronavirus (QCoV), which are evolutionarily distant from respiratory avian coronaviruses based on the viral attachment protein spike (S1). We profiled the binding of recombinantly expressed S1 proteins of TCoV, GfCoV, and QCoV to tissues of their respective hosts. Protein histochemistry showed that the tissue binding specificity of S1 proteins of turkey, quail, and guineafowl CoVs was limited to intestinal tissues of each particular host, in accordance with the reported pathogenicity of these viruses in vivo. Glycan array analyses revealed that, in contrast to the S1 protein of IBV, S1 proteins of enteric gammacoronaviruses recognize a unique set of nonsialylated type 2 poly-N-acetyl-lactosamines. Lectin histochemistry as well as tissue binding patterns of TCoV S1 further indicated that these complex N-glycans are prominently expressed on the intestinal tract of various avian species. In conclusion, our data demonstrate not only that enteric gammacoronaviruses recognize a novel glycan receptor but also that enterotropism may be correlated with the high specificity of spike proteins for such glycans expressed in the intestines of the avian host. IMPORTANCE Avian coronaviruses are economically important viruses for the poultry industry. While infectious bronchitis virus (IBV), a respiratory pathogen of chickens, is rather well known, other viruses of the genus Gammacoronavirus, including those causing enteric disease, are hardly studied. In turkey, guineafowl, and quail, coronaviruses have been reported to be the major causative agent of enteric diseases. Specifically, turkey coronavirus outbreaks have been reported in North America, Europe, and Australia for several decades. Recently, a gammacoronavirus was isolated from guineafowl with fulminating disease. To date, it is not clear why these avian coronaviruses are enteropathogenic, whereas other closely related avian coronaviruses like IBV cause respiratory disease. A comprehensive understanding of the tropism and pathogenicity of these viruses explained by their receptor specificity and receptor expression on tissues was therefore needed. Here, we identify a novel glycan receptor for enteric avian coronaviruses, which will further support the development of vaccines.",,"['Ambepitiya Wickramasinghe, I. N.', 'de Vries, R. P.', 'Weerts, E. A. W. S.', 'van Beurden, S. J.', 'Peng, W.', 'McBride, R.', 'Ducatez, M.', 'Guy, J.', 'Brown, P.', 'Eterradossi, N.', 'Gröne, A.', 'Paulson, J. C.', 'Verheije, M. H.']",,,,
,PMC,Characterization of Two Human Monoclonal Antibodies Neutralizing Influenza A H7N9 Viruses,http://dx.doi.org/10.1128/JVI.01295-15,PMC4524084,,,"H7N9 was a cause of significant global health concern due to its severe infection and approximately 35% mortality in humans. By screening a Fab antibody phage library derived from patients who recovered from H7N9 infections, we characterized two human monoclonal antibodies (HuMAbs), HNIgGD5 and HNIgGH8. The epitope of these two antibodies was dependent on two residues in the receptor binding site at positions V186 and L226 of the hemagglutinin glycoprotein. Both antibodies possessed high neutralizing activity.",,"['Wang, Jianmin', 'Chen, Zhe', 'Bao, Linlin', 'Zhang, Weijia', 'Xue, Ying', 'Pang, XingHuo', 'Zhang, Xi', 'Qin, Chuan', 'Jin, Qi']",,,,
,PMC,Two Mutations Were Critical for Bat-to-Human Transmission of Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.01279-15,PMC4524054,,,"To understand how Middle East respiratory syndrome coronavirus (MERS-CoV) transmitted from bats to humans, we compared the virus surface spikes of MERS-CoV and a related bat coronavirus, HKU4. Although HKU4 spike cannot mediate viral entry into human cells, two mutations enabled it to do so by allowing it to be activated by human proteases. These mutations are present in MERS-CoV spike, explaining why MERS-CoV infects human cells. These mutations therefore played critical roles in the bat-to-human transmission of MERS-CoV, either directly or through intermediate hosts.",,"['Yang, Yang', 'Liu, Chang', 'Du, Lanying', 'Jiang, Shibo', 'Shi, Zhengli', 'Baric, Ralph S.', 'Li, Fang']",,,,
,PMC,The crucial role of vitamin C and its transporter (SVCT2) in bone marrow stromal cell autophagy and apoptosis,http://dx.doi.org/10.1016/j.scr.2015.06.002,PMC4824057,,,"Vitamin C is an antioxidant that plays a vital role in various biological processes including bone formation. Previously, we reported that vitamin C is transported into bone marrow stromal cells (BMSCs) through the sodium dependent Vitamin C Transporter 2 (SVCT2) and this transporter plays an important role in osteogenic differentiation. Furthermore, this transporter is regulated by oxidative stress. To date, however, the exact role of vitamin C and its transporter (SVCT2) in ROS regulated autophagy and apoptosis in BMSCs is poorly understood. In the present study, we observed that oxidative stress decreased survival of BMSCs in a dose-dependent manner and induced growth arrest in the G1 phase of the cell cycle. These effects were accompanied by the induction of autophagy, confirmed by P62 and LC3B protein level and punctate GFP–LC3B distribution. The supplementation of vitamin C significantly rescued the BMSCs from oxidative stress by regulating autophagy. Knockdown of the SVCT2 transporter in BMSCs synergistically decreased cell survival even under low oxidative stress conditions. Also, supplementing vitamin C failed to rescue cells from stress. Our results reveal that the SVCT2 transporter plays a vital role in the mechanism of BMSC survival under stress conditions. Altogether, this study has given new insight into the role of the SVCT2 transporter in oxidative stress related autophagy and apoptosis in BMSCs.",,"['Sangani, Rajnikumar', 'Periyasamy-Thandavan, Sudharsan', 'Pathania, Rajneesh', 'Ahmad, Saif', 'Kutiyanawalla, Ammar', 'Kolhe, Ravindra', 'Bhattacharyya, Maryka H.', 'Chutkan, Norman', 'Hunter, Monte', 'Hill, William D.', 'Hamrick, Mark', 'Isales, Carlos', 'Fulzele, Sadanand']",,,,
,PMC,The Role of Phosphodiesterase 12 (PDE12) as a Negative Regulator of the Innate Immune Response and the Discovery of Antiviral Inhibitors,http://dx.doi.org/10.1074/jbc.M115.653113,PMC4528132,,,"2′,5′-Oligoadenylate synthetase (OAS) enzymes and RNase-L constitute a major effector arm of interferon (IFN)-mediated antiviral defense. OAS produces a unique oligonucleotide second messenger, 2′,5′-oligoadenylate (2–5A), that binds and activates RNase-L. This pathway is down-regulated by virus- and host-encoded enzymes that degrade 2–5A. Phosphodiesterase 12 (PDE12) was the first cellular 2–5A- degrading enzyme to be purified and described at a molecular level. Inhibition of PDE12 may up-regulate the OAS/RNase-L pathway in response to viral infection resulting in increased resistance to a variety of viral pathogens. We generated a PDE12-null cell line, HeLaΔPDE12, using transcription activator-like effector nuclease-mediated gene inactivation. This cell line has increased 2–5A levels in response to IFN and poly(I-C), a double-stranded RNA mimic compared with the parental cell line. Moreover, HeLaΔPDE12 cells were resistant to viral pathogens, including encephalomyocarditis virus, human rhinovirus, and respiratory syncytial virus. Based on these results, we used DNA-encoded chemical library screening to identify starting points for inhibitor lead optimization. Compounds derived from this effort raise 2–5A levels and exhibit antiviral activity comparable with the effects observed with PDE12 gene inactivation. The crystal structure of PDE12 complexed with an inhibitor was solved providing insights into the structure-activity relationships of inhibitor potency and selectivity.",,"['Wood, Edgar R.', 'Bledsoe, Randy', 'Chai, Jing', 'Daka, Philias', 'Deng, Hongfeng', 'Ding, Yun', 'Harris-Gurley, Sarah', 'Kryn, Luz Helena', 'Nartey, Eldridge', 'Nichols, James', 'Nolte, Robert T.', 'Prabhu, Ninad', 'Rise, Cecil', 'Sheahan, Timothy', 'Shotwell, J. Brad', 'Smith, Danielle', 'Tai, Vince', 'Taylor, J. David', 'Tomberlin, Ginger', 'Wang, Liping', 'Wisely, Bruce', 'You, Shihyun', 'Xia, Bing', 'Dickson, Hamilton']",,,,
,PMC,Ligand-induced Dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 Protease (3CL(pro)): IMPLICATIONS FOR nsp5 REGULATION AND THE DEVELOPMENT OF ANTIVIRALS,http://dx.doi.org/10.1074/jbc.M115.651463,PMC4528106,,,"All coronaviruses, including the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) from the β-CoV subgroup, require the proteolytic activity of the nsp5 protease (also known as 3C-like protease, 3CL(pro)) during virus replication, making it a high value target for the development of anti-coronavirus therapeutics. Kinetic studies indicate that in contrast to 3CL(pro) from other β-CoV 2c members, including HKU4 and HKU5, MERS-CoV 3CL(pro) is less efficient at processing a peptide substrate due to MERS-CoV 3CL(pro) being a weakly associated dimer. Conversely, HKU4, HKU5, and SARS-CoV 3CL(pro) enzymes are tightly associated dimers. Analytical ultracentrifugation studies support that MERS-CoV 3CL(pro) is a weakly associated dimer (K(d) ∼52 μm) with a slow off-rate. Peptidomimetic inhibitors of MERS-CoV 3CL(pro) were synthesized and utilized in analytical ultracentrifugation experiments and demonstrate that MERS-CoV 3CL(pro) undergoes significant ligand-induced dimerization. Kinetic studies also revealed that designed reversible inhibitors act as activators at a low compound concentration as a result of induced dimerization. Primary sequence comparisons and x-ray structural analyses of two MERS-CoV 3CLpro and inhibitor complexes, determined to 1.6 Å, reveal remarkable structural similarity of the dimer interface with 3CL(pro) from HKU4-CoV and HKU5-CoV. Despite this structural similarity, substantial differences in the dimerization ability suggest that long range interactions by the nonconserved amino acids distant from the dimer interface may control MERS-CoV 3CL(pro) dimerization. Activation of MERS-CoV 3CL(pro) through ligand-induced dimerization appears to be unique within the genogroup 2c and may potentially increase the complexity in the development of MERS-CoV 3CL(pro) inhibitors as antiviral agents.",,"['Tomar, Sakshi', 'Johnston, Melanie L.', 'St. John, Sarah E.', 'Osswald, Heather L.', 'Nyalapatla, Prasanth R.', 'Paul, Lake N.', 'Ghosh, Arun K.', 'Denison, Mark R.', 'Mesecar, Andrew D.']",,,,
,PMC,Protective Effect of Intranasal Regimens Containing Peptidic Middle East Respiratory Syndrome Coronavirus Fusion Inhibitor Against MERS-CoV Infection,http://dx.doi.org/10.1093/infdis/jiv325,PMC4655857,,,"To gain entry into the target cell, Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) uses its spike (S) protein S2 subunit to fuse with the plasma or endosomal membrane. Previous work identified a peptide derived from the heptad repeat (HR) 2 domain in S2 subunit, HR2P, which potently blocked MERS-CoV S protein–mediated membrane fusion. Here, we tested an HR2P analogue with improved pharmaceutical property, HR2P-M2, for its inhibitory activity against MERS-CoV infection in vitro and in vivo. HR2P-M2 was highly effective in inhibiting MERS-CoV S protein–mediated cell-cell fusion and infection by pseudoviruses expressing MERS-CoV S protein with or without mutation in the HR1 region. It interacted with the HR1 peptide to form stable α-helical complex and blocked six-helix bundle formation between the HR1 and HR2 domains in the viral S protein. Intranasally administered HR2P-M2 effectively protected adenovirus serotype-5–human dipeptidyl peptidase 4–transduced mice from infection by MERS-CoV strains with or without mutations in the HR1 region of S protein, with >1000-fold reduction of viral titers in lung, and the protection was enhanced by combining HR2P-M2 with interferon β. These results indicate that this combination regimen merits further development to prevent MERS in high-risk populations, including healthcare workers and patient family members, and to treat MERS-CoV–infected patients.",,"['Channappanavar, Rudragouda', 'Lu, Lu', 'Xia, Shuai', 'Du, Lanying', 'Meyerholz, David K.', 'Perlman, Stanley', 'Jiang, Shibo']",,,,
,PMC,Generation of Recombinant Human IgG Monoclonal Antibodies from Immortalized Sorted B Cells,http://dx.doi.org/10.3791/52830,PMC4545184,,,"Finding new methods for generating human monoclonal antibodies is an active research field that is important for both basic and applied sciences, including the development of immunotherapeutics. However, the techniques to identify and produce such antibodies tend to be arduous and sometimes the heavy and light chain pair of the antibodies are dissociated. Here, we describe a relatively simple, straightforward protocol to produce human recombinant monoclonal antibodies from human peripheral blood mononuclear cells using immortalization with Epstein-Barr Virus (EBV) and Toll-like receptor 9 activation. With an adequate staining, B cells producing antibodies can be isolated for subsequent immortalization and clonal expansion. The antibody transcripts produced by the immortalized B cell clones can be amplified by PCR, sequenced as corresponding heavy and light chain pairs and cloned into immunoglobulin expression vectors. The antibodies obtained with this technique can be powerful tools to study relevant human immune responses, including autoimmunity, and create the basis for new therapeutics.",,"['Nogales-Gadea, Gisela', 'Saxena, Abhishek', 'Hoffmann, Carolin', 'Hounjet, Judith', 'Coenen, Daniëlle', 'Molenaar, Peter', 'Losen, Mario', 'Martinez-Martinez, Pilar']",,,,
,PMC,Chronic reactive gliosis following regulatory T cell depletion during acute MCMV encephalitis,http://dx.doi.org/10.1002/glia.22868,PMC4670295,,,"Long-term, persistent central nervous system inflammation is commonly seen following brain infection. Using a murine model of viral encephalitis (murine cytomegalovirus, MCMV) we have previously shown that post-encephalitic brains are maintained in an inflammatory state consisting of glial cell reactivity, retention of brain-infiltrating tissue-resident memory CD8(+) T-cells, and long-term persistence of antibody-producing cells of the B-lineage. Here, we report that this neuroinflammation occurs concomitantly with accumulation and retention of immunosuppressive regulatory T-cells (Tregs), and is exacerbated following their ablation. However, the extent to which these Tregs function to control neuroimmune activation following MCMV encephalitis is unknown. In this study, we used Foxp3-diphtheria toxin receptor-GFP (Foxp3-DTR-GFP) transgenic mice, which upon administration of low-dose diphtheria toxin (DTx) results in the specific depletion of Tregs, to investigate their function. We found treatment with DTx during the acute phase of viral brain infection (0 – 4 dpi) resulted in depletion of Tregs from the brain, exacerbation of encephalitis (i.e., increased presence of CD4(+) and CD8(+) T-cells), and chronic reactive phenotypes of resident glial cells (i.e., elevated MHC class II as well as PD-L1 levels, sustained microgliosis, and increased glial fibrillary acidic protein (GFAP) expression on astrocytes) vs. untreated, infected animals. This chronic proinflammatory environment was associated with reduced cognitive performance in spatial learning and memory tasks (Barnes Maze) by convalescent animals. These data demonstrate that chronic glial cell activation, unremitting post-encephalitic neuroinflammation, and its associated long-term neurological sequelae in response to viral brain infection are modulated by the immunoregulatory properties of Tregs.",,"['Lokensgard, James R.', 'Schachtele, Scott J.', 'Mutnal, Manohar B.', 'Sheng, Wen S.', 'Prasad, Sujata', 'Hu, Shuxian']",,,,
,PMC,Optimizing the design of protein nanoparticles as carriers for vaccine applications,http://dx.doi.org/10.1016/j.nano.2015.05.003,PMC4587294,,,"Successful vaccine development remains a huge challenge for infectious diseases such as malaria, HIV and influenza. As a novel way to present antigenic epitopes to the immune system, we have developed icosahedral self-assembling protein nanoparticles (SAPNs) to serve as a prototypical vaccine platform for infectious diseases. Here we examine some biophysical factors that affect the self-assembly of these nanoparticles, which have as basic building blocks coiled-coil oligomerization domains joined by a short linker region. Relying on in silico computer modeling predictions, we selected five different linker regions from the RCSB protein database that connect oligomerization domains, and then further studied the self-assembly and stability of in vitro produced nanoparticles through biophysical characterization of formed particles. One design in particular, T2i88, revealed excellent self-assembly and homogeneity thus paving the way towards a more optimized nanoparticle for vaccine applications.",,"['Doll, Tais A.P.F.', 'Neef, Tobias', 'Duong, Nha', 'Lanar, David E.', 'Ringler, Philippe', 'Müller, Shirley A.', 'Burkhard, Peter']",,,,
,PMC,"A Kinome-Wide Small Interfering RNA Screen Identifies Proviral and Antiviral Host Factors in Severe Acute Respiratory Syndrome Coronavirus Replication, Including Double-Stranded RNA-Activated Protein Kinase and Early Secretory Pathway Proteins",http://dx.doi.org/10.1128/JVI.01029-15,PMC4524262,,,"To identify host factors relevant for severe acute respiratory syndrome-coronavirus (SARS-CoV) replication, we performed a small interfering RNA (siRNA) library screen targeting the human kinome. Protein kinases are key regulators of many cellular functions, and the systematic knockdown of their expression should provide a broad perspective on factors and pathways promoting or antagonizing coronavirus replication. In addition to 40 proteins that promote SARS-CoV replication, our study identified 90 factors exhibiting an antiviral effect. Pathway analysis grouped subsets of these factors in specific cellular processes, including the innate immune response and the metabolism of complex lipids, which appear to play a role in SARS-CoV infection. Several factors were selected for in-depth validation in follow-up experiments. In cells depleted for the β2 subunit of the coatomer protein complex (COPB2), the strongest proviral hit, we observed reduced SARS-CoV protein expression and a >2-log reduction in virus yield. Knockdown of the COPB2-related proteins COPB1 and Golgi-specific brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1) also suggested that COPI-coated vesicles and/or the early secretory pathway are important for SARS-CoV replication. Depletion of the antiviral double-stranded RNA-activated protein kinase (PKR) enhanced virus replication in the primary screen, and validation experiments confirmed increased SARS-CoV protein expression and virus production upon PKR depletion. In addition, cyclin-dependent kinase 6 (CDK6) was identified as a novel antiviral host factor in SARS-CoV replication. The inventory of pro- and antiviral host factors and pathways described here substantiates and expands our understanding of SARS-CoV replication and may contribute to the identification of novel targets for antiviral therapy. IMPORTANCE Replication of all viruses, including SARS-CoV, depends on and is influenced by cellular pathways. Although substantial progress has been made in dissecting the coronavirus replicative cycle, our understanding of the host factors that stimulate (proviral factors) or restrict (antiviral factors) infection remains far from complete. To study the role of host proteins in SARS-CoV infection, we set out to systematically identify kinase-regulated processes that influence virus replication. Protein kinases are key regulators in signal transduction, controlling a wide variety of cellular processes, and many of them are targets of approved drugs and other compounds. Our screen identified a variety of hits and will form the basis for more detailed follow-up studies that should contribute to a better understanding of SARS-CoV replication and coronavirus-host interactions in general. The identified factors could be interesting targets for the development of host-directed antiviral therapy to treat infections with SARS-CoV or other pathogenic coronaviruses.",,"['de Wilde, Adriaan H.', 'Wannee, Kazimier F.', 'Scholte, Florine E. M.', 'Goeman, Jelle J.', 'ten Dijke, Peter', 'Snijder, Eric J.', 'Kikkert, Marjolein', 'van Hemert, Martijn J.']",,,,
,PMC,Coronavirus nsp10/nsp16 Methyltransferase Can Be Targeted by nsp10-Derived Peptide In Vitro and In Vivo To Reduce Replication and Pathogenesis,http://dx.doi.org/10.1128/JVI.00948-15,PMC4524257,,,"The 5′ cap structures of eukaryotic mRNAs are important for RNA stability and protein translation. Many viruses that replicate in the cytoplasm of eukaryotes have evolved 2′-O-methyltransferases (2′-O-MTase) to autonomously modify their mRNAs and carry a cap-1 structure (m7GpppNm) at the 5′ end, thereby facilitating viral replication and escaping innate immune recognition in host cells. Previous studies showed that the 2′-O-MTase activity of severe acute respiratory syndrome coronavirus (SARS-CoV) nonstructural protein 16 (nsp16) needs to be activated by nsp10, whereas nsp16 of feline coronavirus (FCoV) alone possesses 2′-O-MTase activity (E. Decroly et al., J Virol 82:8071–8084, 2008, http://dx.doi.org/10.1128/JVI.00407-08; M. Bouvet et al., PLoS Pathog 6:e1000863, 2010, http://dx.doi.org/10.1371/journal.ppat.1000863; E. Decroly et al., PLoS Pathog 7:e1002059, 2011, http://dx.doi.org/10.1371/journal.ppat.1002059; Y. Chen et al., PLoS Pathog 7:e1002294, 2011, http://dx.doi.org/10.1371/journal.ppat.1002294) . In this study, we demonstrate that stimulation of nsp16 2′-O-MTase activity by nsp10 is a universal and conserved mechanism in coronaviruses, including FCoV, and that nsp10 is functionally interchangeable in the stimulation of nsp16 of different coronaviruses. Based on our current and previous studies, we designed a peptide (TP29) from the sequence of the interaction interface of mouse hepatitis virus (MHV) nsp10 and demonstrated that the peptide inhibits the 2′-O-MTase activity of different coronaviruses in biochemical assays and the viral replication in MHV infection and SARS-CoV replicon models. Interestingly, the peptide TP29 exerted robust inhibitory effects in vivo in MHV-infected mice by impairing MHV virulence and pathogenesis through suppressing virus replication and enhancing type I interferon production at an early stage of infection. Therefore, as a proof of principle, the current results indicate that coronavirus 2′-O-MTase activity can be targeted in vitro and in vivo. IMPORTANCE Coronaviruses are important pathogens of animals and human with high zoonotic potential. SARS-CoV encodes the 2′-O-MTase that is composed of the catalytic subunit nsp16 and the stimulatory subunit nsp10 and plays an important role in virus genome replication and evasion from innate immunity. Our current results demonstrate that stimulation of nsp16 2′-O-MTase activity by nsp10 is a common mechanism for coronaviruses, and nsp10 is functionally interchangeable in the stimulation of nsp16 among different coronaviruses, which underlies the rationale for developing inhibitory peptides. We demonstrate that a peptide derived from the nsp16-interacting domain of MHV nsp10 could inhibit 2′-O-MTase activity of different coronaviruses in vitro and viral replication of MHV and SARS-CoV replicon in cell culture, and it could strongly inhibit virus replication and pathogenesis in MHV-infected mice. This work makes it possible to develop broad-spectrum peptide inhibitors by targeting the nsp16/nsp10 2′-O-MTase of coronaviruses.",,"['Wang, Yi', 'Sun, Ying', 'Wu, Andong', 'Xu, Shan', 'Pan, Ruangang', 'Zeng, Cong', 'Jin, Xu', 'Ge, Xingyi', 'Shi, Zhengli', 'Ahola, Tero', 'Chen, Yu', 'Guo, Deyin']",,,,
,PMC,Distinct Immune Responses in Resistant and Susceptible Strains of Mice during Neurovirulent Alphavirus Encephalomyelitis,http://dx.doi.org/10.1128/JVI.00173-15,PMC4524229,,,"Susceptibility to alphavirus encephalomyelitis is dependent on a variety of factors, including the genetic background of the host. Neuroadapted Sindbis virus (NSV) causes uniformly fatal disease in adult C57BL/6 (B6) mice, but adult BALB/c (Bc) mice recover from infection. In B6 mice, fatal encephalomyelitis is immune mediated rather than a direct result of virus infection. To identify the immunological determinants of host susceptibility to fatal NSV-induced encephalomyelitis, we compared virus titers and immune responses in adult B6 and Bc mice infected intranasally with NSV. B6 mice had higher levels of virus replication, higher levels of type I interferon (IFN), and slower virus clearance than did Bc mice. B6 mice had more neuronal apoptosis, more severe neurologic disease, and higher mortality than Bc mice. B6 mice had more infiltration of inflammatory cells and higher levels of IL1b, IL-6, TNFa, Csf2, and CCL2 mRNAs and interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), IFN-γ, and C-C motif ligand 2 (CCL2) protein in brains than Bc mice. However, Bc mice had more brain antibody at day 7 and a higher percentage of CD4(+) T cells. CD4(+) T cells in the brains of Bc mice included fewer Th17 cells and more regulatory T cells (Tregs) producing IL-10 than B6 mice, accompanied by higher levels of Il2 and Cxcl10 mRNAs. In the absence of IL-10, resistant Bc mice became susceptible to fatal encephalomyelitis after NSV infection. These studies demonstrate the importance of the immune response and its regulation in determining host survival during alphavirus encephalomyelitis. IMPORTANCE Mosquito-borne alphavirus infections are an important cause of encephalomyelitis in humans. The severity of disease is dependent both on the strain of the virus and on the age and genetic background of the host. A neurovirulent strain of Sindbis virus causes immune-mediated fatal encephalomyelitis in adult C57BL/6 mice but not in BALB/c mice. To determine the host-dependent immunological mechanisms underlying the differences in susceptibility between these two strains of mice, we compared their immune responses to infection. Resistance to fatal disease in BALB/c mice was associated with better antibody responses, more-rapid virus clearance, fewer Th17 cells, and more-potent regulatory T cell responses than occurred in susceptible C57BL/6 mice. In the absence of interleukin-10, a component of the regulatory immune response, resistant mice became susceptible to lethal disease. This study demonstrates the importance of the immune response and its regulation for host survival during alphavirus encephalomyelitis.",,"['Kulcsar, Kirsten A.', 'Baxter, Victoria K.', 'Abraham, Rachy', 'Nelson, Ashley', 'Griffin, Diane E.']",,,,
,PMC,mRNA Capping by Venezuelan Equine Encephalitis Virus nsP1: Functional Characterization and Implications for Antiviral Research,http://dx.doi.org/10.1128/JVI.00599-15,PMC4524220,,,"Alphaviruses are known to possess a unique viral mRNA capping mechanism involving the viral nonstructural protein nsP1. This enzyme harbors methyltransferase (MTase) and nsP1 guanylylation (GT) activities catalyzing the transfer of the methyl group from S-adenosylmethionine (AdoMet) to the N7 position of a GTP molecule followed by the formation of an m(7)GMP-nsP1 adduct. Subsequent transfer of m(7)GMP onto the 5′ end of the viral mRNA has not been demonstrated in vitro yet. Here we report the biochemical characterization of Venezuelan equine encephalitis virus (VEEV) nsP1. We have developed enzymatic assays uncoupling the different reactions steps catalyzed by nsP1. The MTase and GT reaction activities were followed using a nonhydrolyzable GTP (GIDP) substrate and an original Western blot assay using anti-m(3)G/m(7)G-cap monoclonal antibody, respectively. The GT reaction is stimulated by S-adenosyl-l-homocysteine (Ado-Hcy), the product of the preceding MTase reaction, and metallic ions. The covalent linking between nsP1 and m(7)GMP involves a phosphamide bond between the nucleotide and a histidine residue. Final guanylyltransfer onto RNA was observed for the first time with an alphavirus nsP1 using a 5′-diphosphate RNA oligonucleotide whose sequence corresponds to the 5′ end of the viral genome. Alanine scanning mutagenesis of residues H37, H45, D63, E118, Y285, D354, R365, N369, and N375 revealed their respective roles in MT and GT reactions. Finally, the inhibitory effects of sinefungin, aurintricarboxylic acid (ATA), and ribavirin triphosphate on MTase and capping reactions were investigated, providing possible avenues for antiviral research. IMPORTANCE Emergence or reemergence of alphaviruses represents a serious health concern, and the elucidation of their replication mechanisms is a prerequisite for the development of specific inhibitors targeting viral enzymes. In particular, alphaviruses are able, through an original reaction sequence, to add to their mRNA a cap required for their protection against cellular nucleases and initiation of viral proteins translation. In this study, the capping of a 5′ diphosphate synthetic RNA mimicking the 5′ end of an alphavirus mRNA was observed in vitro for the first time. The different steps for this capping are performed by the nonstructural protein 1 (nsP1). Reference compounds known to target the viral capping inhibited nsP1 enzymatic functions, highlighting the value of this enzyme in antiviral development.",,"['Li, Changqing', 'Guillén, Jaime', 'Rabah, Nadia', 'Blanjoie, Alexandre', 'Debart, Françoise', 'Vasseur, Jean-Jacques', 'Canard, Bruno', 'Decroly, Etienne', 'Coutard, Bruno']",,,,
,PMC,Middle East Respiratory Syndrome,http://dx.doi.org/10.1016/S0140-6736(15)60454-8,PMC4721578,,,"The Middle East Respiratory Syndrome (MERS) is a newly recognized highly lethal respiratory disease caused by a novel single stranded, positive sense RNA betacoronavirus (MERS-CoV). Dromedary camels, host species for MERS-CoV are implicated in the direct or indirect transmission to humans, although the exact mode of transmission remains unknown. First isolated from a patient who died from a severe respiratory illness in June 2012 in Jeddah, Saudi Arabia, as of 16 February 2015, 983 laboratory-confirmed cases of MERS-CoV (360 deaths; 36.6% mortality) were reported to the WHO. Cases have been acquired in both the community and hospitals with limited human-to-human transmission reported in the community. Whilst the majority of MERS cases have occurred in Saudi Arabia and the United Arab Emirates, cases have been reported from Europe, USA and Asia in people who traveled from the Middle East or their contacts. Clinical features of MERS range from asymptomatic or mild disease to acute respiratory distress syndrome and multi-organ failure resulting in death, especially in individuals with underlying co-morbidities. There is no specific drug treatment for MERS and infection prevention and control measures are crucial to prevent spread of MERS-CoV in health care facilities. MERS-CoV continues to be an endemic,low level public health threat. However, the concern remains that the virus could mutate to exhibit increased interhuman transmissibility, increasing pandemic potential. Our seminar presents an overview of current knowledge and perspectives on the epidemiology, virology, mode of transmission, pathogen-host responses, clinical features, diagnosis and development of new drugs and vaccines.",,"['Zumla, Alimuddin', 'Hui, David S', 'Perlman, Stanley']",,,,
,PMC,Mild encephalopathy with reversible splenial lesion in a patient with influenza A infection—first report in an adult patient in the USA,http://dx.doi.org/10.1136/bcr-2015-210197,PMC4460435,,,"We present a case of a 51-year-old man with panhypopituarism who developed clinically mild encephalopathy with a lesion in the splenium of the corpus callosum, in the setting of acute influenza A infection. The patient's initial presentation included hypernatraemia due to pre-existing iatrogenic central diabetes insipidus. Despite adequate treatment of hypernatraemia, his course was complicated by otherwise unexplained mild encephalopathy. Brain MRI revealed a diffusion restricted lesion in the splenium of the corpus callosum. This presentation was consistent with mild encephalopathy with reversible splenial lesion (MERS). The patient subsequently tested positive for influenza A. This is the first reported case of MERS syndrome due to influenza A infection in an adult patient in the USA. Mild encephalopathy associated with influenza A infection and a reversible splenial lesion of the corpus callosum has a favourable prognosis and resolves spontaneously.",,"['Wang, Jonathan', 'Stewart, Earl', 'Dapaah-Afriyie, Kwame', 'Finn, Arkadiy']",,,,
,PMC,T-cell intracellular antigens in health and disease,http://dx.doi.org/10.1080/15384101.2015.1053668,PMC4614917,,,"T-cell intracellular antigen 1 (TIA1) and TIA1-related/like protein (TIAR/TIAL1) are 2 proteins discovered in 1991 as components of cytotoxic T lymphocyte granules. They act in the nucleus as regulators of transcription and pre-mRNA splicing. In the cytoplasm, TIA1 and TIAR regulate and/or modulate the location, stability and/or translation of mRNAs. As knowledge of the different genes regulated by these proteins and the cellular/biological programs in which they are involved increases, it is evident that these antigens are key players in human physiology and pathology. This review will discuss the latest developments in the field, with physiopathological relevance, that point to novel roles for these regulators in the molecular and cell biology of higher eukaryotes.",,"['Sánchez-Jiménez, Carmen', 'Izquierdo, José M']",,,,
,PMC,The context of host competence: a role for plasticity in host–parasite dynamics,http://dx.doi.org/10.1016/j.pt.2015.05.002,PMC4567474,,,"Even apparently similar hosts can respond differently to the same parasites. Some individuals or specific groups of individuals disproportionately affect disease dynamics. Understanding the sources of among-host heterogeneity in the ability to transmit parasites would improve disease management. A major source of host variation might be phenotypic plasticity – the tendency for phenotypes to change across different environments. Plasticity might be as important as, or even more important than, genetic change, especially in light of human modifications of the environment, because it can occur on a more rapid timescale than evolution. We argue that variation in phenotypic plasticity among and within species strongly contributes to epidemiological dynamics when parasites are shared among multiple hosts, which is often the case.",,"['Gervasi, Stephanie S.', 'Civitello, David J.', 'Kilvitis, Holly J.', 'Martin, Lynn B.']",,,,
,PMC,Molecular Pathogenesis Lessons from the World of Infectious Diseases Research,http://dx.doi.org/10.1016/j.ajpath.2015.03.004,PMC4450309,,,"This Guest Editorial introduces this month's special Infectious Disease Theme Issue, a series of reviews focusing on the molecular pathogenic processes of four representative pathogens, including two bacteria (brucellae and Staphylococcus aureus), a virus (influenza), and a parasite (Trypanosoma cruzi).",,"['Musser, James M.', 'DeLeo, Frank R.']",,,,
,PMC,SARS hCoV papain-like protease is a unique Lys48 linkage-specific di-distributive deubiquitinating enzyme,http://dx.doi.org/10.1042/BJ20141170,PMC4447217,,,"Ubiquitin (Ub) and the ubiquitin-like modifier interferon stimulated gene 15 (ISG15) participate in the host defense of viral infections. Viruses, including the Severe Acute Respiratory Syndrome human coronavirus (SARS hCoV), have co-opted Ub/ISG15-conjugation pathways for their own advantage or have evolved effector proteins to counter pro-inflammatory properties of Ub/ISG15-conjugated host proteins. Here, we compare substrate specificities of the papain-like protease (PLpro) from the recently emerged Middle Eastern Respiratory Syndrome (MERS) hCoV to the related protease from SARS, SARS PLpro. Through biochemical assays, we show that similar to SARS PLpro, MERS PLpro is both a deubiquitinating and a deISGylating enzyme. Further analysis of the intrinsic deubiquitinating enzyme (DUB) activity of these viral proteases revealed unique differences between the recognition and cleavage specificities of polyUb chains. First, MERS PLpro shows broad linkage specificity for the cleavage of polyUb chains, while SARS PLpro prefers to cleave Lys48-linked polyUb chains. Second, MERS PLpro cleaves polyUb chains in a “mono-distributive” manner (one Ub at a time), and SARS PLpro prefers to cleave K48-linked poly-Ub chains by sensing a di-Ub moiety as a minimal recognition element using a “di-distributive” cleavage mechanism. The di-distributive cleavage mechanism for SARS PLpro appears to be uncommon among USP-family DUBs, as related USP family members from humans do not display such a mechanism. We propose that these intrinsic enzymatic differences between SARS and MERS PLpro will help identify pro-inflammatory substrates of these viral DUBs and can guide in the design of therapeutics to combat infection by coronaviruses.",,"['Békés, Miklós', 'Rut, Wioletta', 'Kasperkiewicz, Paulina', 'Mulder, Monique P. C.', 'Ovaa, Huib', 'Drag, Marcin', 'Lima, Christopher D.', 'Huang, Tony T.']",,,,
,PMC,Dengue Virus Control of Type I IFN Responses: A History of Manipulation and Control,http://dx.doi.org/10.1089/jir.2014.0129,PMC4490770,,,"The arthropod-borne diseases caused by dengue virus (DENV) are a major and emerging problem of public health worldwide. Infection with DENV causes a series of clinical manifestations ranging from mild flu syndrome to severe diseases that include hemorrhage and shock. It has been demonstrated that the innate immune response plays a key role in DENV pathogenesis. However, in recent years, it was shown that DENV evades the innate immune response by blocking type I interferon (IFN-I). It has been demonstrated that DENV can inhibit both the production and the signaling of IFN-I. The viral proteins, NS2A and NS3, inhibit IFN-I production by degrading cellular signaling molecules. In addition, the viral proteins, NS2A, NS4A, NS4B, and NS5, can inhibit IFN-I signaling by blocking the phosphorylation of the STAT1 and STAT2 molecules. Finally, NS5 mediates the degradation of STAT2 using the proteasome machinery. In this study, we briefly review the most recent insights regarding the IFN-I response to DENV infection and its implication for pathogenesis.",,"['Castillo Ramirez, Jorge Andrés', 'Urcuqui-Inchima, Silvio']",,,,
,PMC,Risk of urinary tract infection in infants and children with acute bronchiolitis,,PMC4472059,,,"OBJECTIVES: To estimate the prevalence of urinary tract infection in infants and children with bronchiolitis. METHODS: A retrospective cross-sectional study involving patients zero to 24 months of age who were hospitalized with acute bronchiolitis was conducted. RESULTS: A total of 835 paediatric patients with acute bronchiolitis were admitted to the paediatric ward between January 2010 and December 2012. The mean (± SD) age at diagnosis was 3.47±2.99 months. There were 325 (39%) girls and 510 (61%) boys. For the purpose of data analysis, the patient population was divided into three groups: group 1 included children hospitalized with respiratory syncytial virus (RSV) bronchiolitis; group 2 included children hospitalized with clinical bronchiolitis with no virus detected; and group 3 included children hospitalized with clinical bronchiolitis due to a respiratory virus other than RSV. Results revealed that urinary tract infection was present in 10% of patients, and was most common in group 3 (13.4%) followed by group 2 (9.7%), and was least common in group 1 (6%) (P=0.030). CONCLUSIONS: The possibility of a urinary tract infection should be considered in a febrile child with a diagnosis of bronchiolitis, particularly if the trigger is a respiratory virus other than RSV.",,"['Hendaus, Mohamed A', 'Alhammadi, Ahmed H', 'Khalifa, Mohamed S', 'Muneer, Eshan', 'Chandra, Prem']",,,,
,PMC,Bordetella Pertussis is an Uncommon Pathogen in Children Hospitalized with Bronchiolitis During the Winter Season,http://dx.doi.org/10.1097/INF.0000000000000596,PMC4435848,,,"BACKGROUND: In the United States (U.S.), Bordetella pertussis incidence has increased. Cough and apnea are common findings in pertussis and also in bronchiolitis, the most common cause of hospitalization in U.S. infants. The objective was to determine the prevalence of B. pertussis infection in children hospitalized with bronchiolitis and to describe its clinical course. METHODS: Children hospitalized with bronchiolitis and age <2 years were eligible for a prospective, multicenter cohort study during three consecutive winter seasons (November to March) from 2007 to 2010. 16 sites in 12 states participated using a standardized enrollment protocol. Families were asked the 2010 Centers for Disease Control and Prevention (CDC) pertussis classification questions. Nasopharyngeal aspirates were obtained and tested by real time polymerase chain reaction for 16 viruses, Mycoplama pneumoniae and B. pertussis. RESULTS: 2068 (94%) of 2,207 children had one or more respiratory pathogens. B. pertussis was identified in 4 children (0.2%; 95% CI, 0.1–0.5%) with 3 having a viral co-infection. All 4 were younger than four months; 2 met the CDC definition of probable pertussis, and 3 had received at least one dose of an acellular pertussis vaccine. During the hospitalization, 2 had paroxysmal cough, 1 required ICU care, and the median length of stay was 13 days. CONCLUSION: Our data support that B. pertussis is an uncommon pathogen in U.S. children hospitalized with bronchiolitis in the winter. Making a diagnosis of pertussis can be challenging because the disease can be atypical, and may not meet the CDC definition of probable infection.",,"['Piedra, Pedro A.', 'Mansbach, Jonathan M.', 'Jewell, Alan M.', 'Thakar, Sneha D.', 'Grant, Cameron C.', 'Sullivan, Ashley F.', 'Espinola, Janice A.', 'Camargo, Carlos A.']",,,,
,PMC,"Protective Efficacy of the Conserved NP, PB1, and M1 Proteins as Immunogens in DNA- and Vaccinia Virus-Based Universal Influenza A Virus Vaccines in Mice",http://dx.doi.org/10.1128/CVI.00091-15,PMC4446406,,,"The conventional hemagglutinin (HA)- and neuraminidase (NA)-based influenza vaccines need to be updated most years and are ineffective if the glycoprotein HA of the vaccine strains is a mismatch with that of the epidemic strain. Universal vaccines targeting conserved viral components might provide cross-protection and thus complement and improve conventional vaccines. In this study, we generated DNA plasmids and recombinant vaccinia viruses expressing the conserved proteins nucleoprotein (NP), polymerase basic 1 (PB1), and matrix 1 (M1) from influenza virus strain A/Beijing/30/95 (H3N2). BALB/c mice were immunized intramuscularly with a single vaccine based on NP, PB1, or M1 alone or a combination vaccine based on all three antigens and were then challenged with lethal doses of the heterologous influenza virus strain A/PR/8/34 (H1N1). Vaccines based on NP, PB1, and M1 provided complete or partial protection against challenge with 1.7 50% lethal dose (LD(50)) of PR8 in mice. Of the three antigens, NP-based vaccines induced protection against 5 LD(50) and 10 LD(50) and thus exhibited the greatest protective effect. Universal influenza vaccines based on the combination of NP, PB1, and M1 induced a strong immune response and thus might be an alternative approach to addressing future influenza virus pandemics.",,"['Wang, Wenling', 'Li, Renqing', 'Deng, Yao', 'Lu, Ning', 'Chen, Hong', 'Meng, Xin', 'Wang, Wen', 'Wang, Xiuping', 'Yan, Kexia', 'Qi, Xiangrong', 'Zhang, Xiangmin', 'Xin, Wei', 'Lu, Zhenhua', 'Li, Xueren', 'Bian, Tao', 'Gao, Yingying', 'Tan, Wenjie', 'Ruan, Li']",,,,
,PMC,Gammaretrovirus-Specific Antibodies in Free-Ranging and Captive Namibian Cheetahs,http://dx.doi.org/10.1128/CVI.00705-14,PMC4446404,,,"The cheetah population in Namibia is the largest free-ranging population in the world and a key population for research regarding the health status of this species. We used serological methods and quantitative real-time PCR to test free-ranging and captive Namibian cheetahs for the presence of feline leukemia virus (FeLV), a gammaretrovirus that can be highly aggressive in populations with low genetic diversity, such as cheetahs. We also assessed the presence of antibodies to other gammaretroviruses and the responses to a FeLV vaccine developed for domestic cats. Up to 19% of the free-ranging cheetahs, 27% of the captive nonvaccinated cheetahs, and 86% of the captive vaccinated cheetahs tested positive for FeLV antibodies. FeLV-antibody-positive free-ranging cheetahs also tested positive for Rauscher murine leukemia virus antibodies. Nevertheless, FeLV was not detectable by quantitative real-time PCR and no reverse transcriptase activity was detectable by product-enhanced reverse transcriptase assay in the plasma of cheetahs or the supernatants from cultures of peripheral blood mononuclear cells. The presence of antibodies to gammaretroviruses in clinically healthy specimens may be caused either by infection with a low-pathogenic retrovirus or by the expression of endogenous retroviral sequences. The strong humoral immune responses to FeLV vaccination demonstrate that cheetahs can respond to the vaccine and that vaccination against FeLV infection may be beneficial should FeLV infection ever become a threat, as was seen in Iberian lynx and Florida panthers.",,"['Krengel, Annika', 'Cattori, Valentino', 'Meli, Marina L.', 'Wachter, Bettina', 'Böni, Jürg', 'Bisset, Leslie R.', 'Thalwitzer, Susanne', 'Melzheimer, Jörg', 'Jago, Mark', 'Hofmann-Lehmann, Regina', 'Hofer, Heribert', 'Lutz, Hans']",,,,
,PMC,Letter from the Editor,http://dx.doi.org/10.1080/21645515.2015.1046724,PMC4514335,,,,,"['Ellis, Ronald', 'Weiss, Adam']",,,,
,PMC,"Population Bottlenecks and Pathogen Extinction: “Make This Everyone's Mission to Mars, Including Yours”",http://dx.doi.org/10.1128/JVI.00920-15,PMC4524259,,,"Kapusinszky et al. (J Virol 89:8152–8161, 2015, http://dx.doi.org/10.1128/JVI.00671-15) report that host population bottlenecks may result in pathogen extinction, which provides a compelling argument for an alternative approach to vaccination for the control of virus spread. By comparing the prevalence levels of three viral pathogens in two populations of African green monkeys (AGMs) (Chlorocebus sabaeus) from Africa and two Caribbean Islands, they convincingly show that a major host bottleneck resulted in the eradication of select pathogens from a given host.",,"['Policicchio, Benjamin B.', 'Pandrea, Ivona', 'Apetrei, Cristian']",,,,
,PMC,Protective Efficacy of Recombinant Modified Vaccinia Virus Ankara Delivering Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein,http://dx.doi.org/10.1128/JVI.00614-15,PMC4524222,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease in humans. We tested a recombinant modified vaccinia virus Ankara (MVA) vaccine expressing full-length MERS-CoV spike (S) glycoprotein by immunizing BALB/c mice with either intramuscular or subcutaneous regimens. In all cases, MVA-MERS-S induced MERS-CoV-specific CD8(+) T cells and virus-neutralizing antibodies. Vaccinated mice were protected against MERS-CoV challenge infection after transduction with the human dipeptidyl peptidase 4 receptor. This MERS-CoV infection model demonstrates the safety and efficacy of the candidate vaccine.",,"['Volz, Asisa', 'Kupke, Alexandra', 'Song, Fei', 'Jany, Sylvia', 'Fux, Robert', 'Shams-Eldin, Hosam', 'Schmidt, Jörg', 'Becker, Christin', 'Eickmann, Markus', 'Becker, Stephan', 'Sutter, Gerd']",,,,
,PMC,Surveillance of Acute Respiratory Infections Using Community-Submitted Symptoms and Specimens for Molecular Diagnostic Testing,http://dx.doi.org/10.1371/currents.outbreaks.0371243baa7f3810ba1279e30b96d3b6,PMC4455990,26075141,CC BY,"Participatory systems for surveillance of acute respiratory infection give real-time information about infections circulating in the community, yet to-date are limited to self-reported syndromic information only and lacking methods of linking symptom reports to infection types. We developed the GoViral platform to evaluate whether a cohort of lay volunteers could, and would find it useful to, contribute self-reported symptoms online and to compare specimen types for self-collected diagnostic information of sufficient quality for respiratory infection surveillance. Volunteers were recruited, given a kit (collection materials and customized instructions), instructed to report their symptoms weekly, and when sick with cold or flu-like symptoms, requested to collect specimens (saliva and nasal swab). We compared specimen types for respiratory virus detection sensitivity (via polymerase-chain-reaction) and ease of collection. Participants were surveyed to determine receptivity to participating when sick, to receiving information on the type of pathogen causing their infection and types circulating near them. Between December 1 2013 and March 1 2014, 295 participants enrolled in the study and received a kit. Of those who reported symptoms, half (71) collected and sent specimens for analysis. Participants submitted kits on average 2.30 days (95 CI: 1.65 to 2.96) after symptoms began. We found good concordance between nasal and saliva specimens for multiple pathogens, with few discrepancies. Individuals report that saliva collection is easiest and report that receiving information about what pathogen they, and those near them, have is valued and can shape public health behaviors. Community-submitted specimens can be used for the detection of acute respiratory infection with individuals showing receptivity for participating and interest in a real-time picture of respiratory pathogens near them.",2015 May 27,"['Goff, Jennifer', 'Rowe, Aaron', 'Brownstein, John S.', 'Chunara, Rumi']",PLoS Curr,,,
,PMC,"Disease Detection or Public Opinion Reflection? Content Analysis of Tweets, Other Social Media, and Online Newspapers During the Measles Outbreak in the Netherlands in 2013",http://dx.doi.org/10.2196/jmir.3863,PMC4468573,26013683,CC BY,"BACKGROUND: In May 2013, a measles outbreak began in the Netherlands among Orthodox Protestants who often refuse vaccination for religious reasons. OBJECTIVE: Our aim was to compare the number of messages expressed on Twitter and other social media during the measles outbreak with the number of online news articles and the number of reported measles cases to answer the question if and when social media reflect public opinion patterns versus disease patterns. METHODS: We analyzed measles-related tweets, other social media messages, and online newspaper articles over a 7-month period (April 15 to November 11, 2013) with regard to topic and sentiment. Thematic analysis was used to structure and analyze the topics. RESULTS: There was a stronger correlation between the weekly number of social media messages and the weekly number of online news articles (P<.001 for both tweets and other social media messages) than between the weekly number of social media messages and the weekly number of reported measles cases (P=.003 and P=.048 for tweets and other social media messages, respectively), especially after the summer break. All data sources showed 3 large peaks, possibly triggered by announcements about the measles outbreak by the Dutch National Institute for Public Health and the Environment and statements made by well-known politicians. Most messages informed the public about the measles outbreak (ie, about the number of measles cases) (93/165, 56.4%) followed by messages about preventive measures taken to control the measles spread (47/132, 35.6%). The leading opinion expressed was frustration regarding people who do not vaccinate because of religious reasons (42/88, 48%). CONCLUSIONS: The monitoring of online (social) media might be useful for improving communication policies aiming to preserve vaccination acceptability among the general public. Data extracted from online (social) media provide insight into the opinions that are at a certain moment salient among the public, which enables public health institutes to respond immediately and appropriately to those public concerns. More research is required to develop an automatic coding system that captures content and user’s characteristics that are most relevant to the diseases within the National Immunization Program and related public health events and can inform official responses.",2015 May 26,"['Mollema, Liesbeth', 'Harmsen, Irene Anhai', 'Broekhuizen, Emma', 'Clijnk, Rutger', 'De Melker, Hester', 'Paulussen, Theo', 'Kok, Gerjo', 'Ruiter, Robert', 'Das, Enny']",J Med Internet Res,,,
,PMC,Infectious disease transmission and contact networks in wildlife and livestock,http://dx.doi.org/10.1098/rstb.2014.0107,PMC4410373,,,"The use of social and contact networks to answer basic and applied questions about infectious disease transmission in wildlife and livestock is receiving increased attention. Through social network analysis, we understand that wild animal and livestock populations, including farmed fish and poultry, often have a heterogeneous contact structure owing to social structure or trade networks. Network modelling is a flexible tool used to capture the heterogeneous contacts of a population in order to test hypotheses about the mechanisms of disease transmission, simulate and predict disease spread, and test disease control strategies. This review highlights how to use animal contact data, including social networks, for network modelling, and emphasizes that researchers should have a pathogen of interest in mind before collecting or using contact data. This paper describes the rising popularity of network approaches for understanding transmission dynamics in wild animal and livestock populations; discusses the common mismatch between contact networks as measured in animal behaviour and relevant parasites to match those networks; and highlights knowledge gaps in how to collect and analyse contact data. Opportunities for the future include increased attention to experiments, pathogen genetic markers and novel computational tools.",,"Craft, Meggan E.",,,,
,PMC,"Design, synthesis and evaluation of a series of acyclic fleximer nucleoside analogues with anti-coronavirus activity",http://dx.doi.org/10.1016/j.bmcl.2015.05.039,PMC4466200,,,"A series of doubly flexible nucleoside analogues were designed based on the acyclic sugar scaffold of acyclovir and the flex-base moiety found in the fleximers. The target compounds were evaluated for their antiviral potential and found to inhibit several coronaviruses. Significantly, compound 2 displayed selective antiviral activity (CC(50) > 3x EC(50)) towards human coronavirus (HCoV)-NL63 and Middle East respiratory syndrome-coronavirus, but not severe acute respiratory syndrome-coronavirus. In the case of HCoV-NL63 the activity was highly promising with an EC(50) < 10 μM and a CC(50) > 100 μM. As such, these doubly flexible nucleoside analogues are viewed as a novel new class of drug candidates with potential for potent inhibition of coronaviruses.",,"['Peters, Hannah L.', 'Jochmans, Dirk', 'de Wilde, Adriaan H.', 'Posthuma, Clara C.', 'Snijder, Eric J.', 'Neyts, Johan', 'Seley-Radtke, Katherine L.']",,,,
,PMC,IL-6 trans-signaling increases expression of airways disease genes in airway smooth muscle,http://dx.doi.org/10.1152/ajplung.00288.2014,PMC4504976,,,"Genetic data suggest that IL-6 trans-signaling may have a pathogenic role in the lung; however, the effects of IL-6 trans-signaling on lung effector cells have not been investigated. In this study, human airway smooth muscle (HASM) cells were treated with IL-6 (classical) or IL-6+sIL6R (trans-signaling) for 24 h and gene expression was measured by RNAseq. Intracellular signaling and transcription factor activation were assessed by Western blotting and luciferase assay, respectively. The functional effect of IL-6 trans-signaling was determined by proliferation assay. IL-6 trans-signaling had no effect on phosphoinositide-3 kinase and Erk MAP kinase pathways in HASM cells. Both classical and IL-6 trans-signaling in HASM involves activation of Stat3. However, the kinetics of Stat3 phosphorylation by IL-6 trans-signaling was different than classical IL-6 signaling. This was further reflected in the differential gene expression profile by IL-6 trans-signaling in HASM cells. Under IL-6 trans-signaling conditions 36 genes were upregulated, including PLA2G2A, IL13RA1, MUC1, and SOD2. Four genes, including CCL11, were downregulated at least twofold. The expression of 112 genes was divergent between IL-6 classical and trans-signaling, including the genes HILPDA, NNMT, DAB2, MUC1, WWC1, and VEGFA. Pathway analysis revealed that IL-6 trans-signaling induced expression of genes involved in regulation of airway remodeling, immune response, hypoxia, and glucose metabolism. Treatment of HASM cells with IL-6+sIL6R induced proliferation in a dose-dependent fashion, suggesting a role for IL-6 trans-signaling in asthma pathogenesis. These novel findings demonstrate differential effect of IL-6 trans-signaling on airway cells and identify IL-6 trans-signaling as a potential modifier of airway inflammation and remodeling.",,"['Robinson, Mac B.', 'Deshpande, Deepak A.', 'Chou, Jeffery', 'Cui, Wei', 'Smith, Shelly', 'Langefeld, Carl', 'Hastie, Annette T.', 'Bleecker, Eugene R.', 'Hawkins, Gregory A.']",,,,
,PMC,θ-Defensin RTD-1 improves insulin action and normalizes plasma glucose and FFA levels in diet-induced obese rats,http://dx.doi.org/10.1152/ajpendo.00131.2015,PMC4504933,,,"Inflammation is implicated in metabolic abnormalities in obesity and type 2 diabetes. Because θ-defensins have anti-inflammatory activities, we tested whether RTD-1, a θ-defensin, improves metabolic conditions in diet-induced obesity (DIO). DIO was induced by high-fat feeding in obese-prone CD rats from 4 wk of age. Starting at age 10 wk, the DIO rats were treated with saline or RTD-1 for 4 or 8 wk. DIO rats gained more weight than low-fat-fed controls. RTD-1 treatment did not alter body weight or calorie intake in DIO rats. Plasma glucose, FFA, triglyceride (TG), and insulin levels increased in DIO rats; RTD-1 normalized plasma glucose and FFA levels and showed tendencies to lower plasma insulin and TG levels. Hepatic and skeletal muscle TG contents increased in DIO rats; RTD-1 decreased muscle, but not hepatic, TG content. Insulin sensitivity, estimated using homeostasis model assessment of insulin resistance and the glucose clamp technique, decreased in DIO rats, but this change was markedly reversed by RTD-1. RTD-1 had no significant effects on plasma cytokine/chemokine levels or IL-1β and TNF-α expression in liver or adipose tissues. RTD-1 treatment decreased hepatic expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, suggesting that the effect of RTD-1 on plasma glucose (or insulin action) might be mediated by its effect to decrease hepatic gluconeogenesis. Thus, RTD-1 ameliorated insulin resistance and normalized plasma glucose and FFA levels in DIO rats, supporting the potential of RTD-1 as a novel therapeutic agent for insulin resistance, metabolic syndrome, or type 2 diabetes.",,"['Oh, Young Taek', 'Tran, Dat', 'Buchanan, Thomas A.', 'Selsted, Michael E.', 'Youn, Jang H.']",,,,
,PMC,Journal Watch,http://dx.doi.org/10.1177/1757177415585594,PMC5074115,,,,,"['Storr, Jules', 'Kilpatrick, Claire']",,,,
,PMC,Virus-induced translational arrest through 4EBP1/2-dependent decay of 5′-TOP mRNAs restricts viral infection,http://dx.doi.org/10.1073/pnas.1418805112,PMC4460451,,,"The mosquito-transmitted bunyavirus, Rift Valley fever virus (RVFV), is a highly successful pathogen for which there are no vaccines or therapeutics. Translational arrest is a common antiviral strategy used by hosts. In response, RVFV inhibits two well-known antiviral pathways that attenuate translation during infection, PKR and type I IFN signaling. Despite this, translational arrest occurs during RVFV infection by unknown mechanisms. Here, we find that RVFV infection triggers the decay of core translation machinery mRNAs that possess a 5′-terminal oligopyrimidine (5′-TOP) motif in their 5′-UTR, including mRNAs encoding ribosomal proteins, which leads to a decrease in overall ribosomal protein levels. We find that the RNA decapping enzyme NUDT16 selectively degrades 5′-TOP mRNAs during RVFV infection and this decay is triggered in response to mTOR attenuation via the translational repressor 4EBP1/2 axis. Translational arrest of 5′-TOPs via 4EBP1/2 restricts RVFV replication, and this increased RNA decay results in the loss of visible RNA granules, including P bodies and stress granules. Because RVFV cap-snatches in RNA granules, the increased level of 5′-TOP mRNAs in this compartment leads to snatching of these targets, which are translationally suppressed during infection. Therefore, translation of RVFV mRNAs is compromised by multiple mechanisms during infection. Together, these data present a previously unknown mechanism for translational shutdown in response to viral infection and identify mTOR attenuation as a potential therapeutic avenue against bunyaviral infection.",,"['Hopkins, Kaycie C.', 'Tartell, Michael A.', 'Herrmann, Christin', 'Hackett, Brent A.', 'Taschuk, Frances', 'Panda, Debasis', 'Menghani, Sanjay V.', 'Sabin, Leah R.', 'Cherry, Sara']",,,,
,PMC,Leveraging social networking sites for disease surveillance and public sensing: the case of the 2013 avian influenza A(H7N9) outbreak in China,http://dx.doi.org/10.5365/WPSAR.2015.6.1.013,PMC4542489,,,"We conducted in-depth analysis on the use of a popular Chinese social networking and microblogging site, Sina Weibo, to monitor an avian influenza A(H7N9) outbreak in China and to assess the value of social networking sites in the surveillance of disease outbreaks that occur overseas. Two data sets were employed for our analysis: a line listing of confirmed cases obtained from conventional public health information channels and case information from Weibo posts. Our findings showed that the level of activity on Weibo corresponded with the number of new cases reported. In addition, the reporting of new cases on Weibo was significantly faster than those of conventional reporting sites and non-local news media. A qualitative review of the functions of Weibo also revealed that Weibo enabled timely monitoring of other outbreak-relevant information, provided access to additional crowd-sourced epidemiological information and was leveraged by the local government as an interactive platform for risk communication and monitoring public sentiment on the policy response. Our analysis demonstrated the potential for social networking sites to be used by public health agencies to enhance traditional communicable disease surveillance systems for the global surveillance of overseas public health threats. Social networking sites also can be used by governments for calibration of response policies and measures and for risk communication.",,"['Zhang, Emma Xuxiao', 'Yang, Yinping', 'Di Shang, Richard', 'Simons, Joseph John Pyne', 'Quek, Boon Kiat', 'Yin, Xiao Feng', 'See, Wanhan', 'Oh, Olivia Seen Huey', 'Nandar, Khine Sein Tun', 'Ling, Vivienne Ruo Yun', 'Chan, Pei Pei', 'Wang, Zhaoxia', 'Goh, Rick Siow Mong', 'James, Lyn', 'Tey, Jeannie Su Hui']",,,,
,PMC,Characterization of immune cells and perforin mutations in familiar venous thromboembolism,,PMC4509298,,,"Aim: This study was to carry out exome sequencing in a Han Chinese family with venous thromboembolism. Methods: Three venous thromboembolism (VTE) patients and five members from a Han Chinese family were evaluated by exome sequencing. Results: Among the 3 VTE patients, mutations of 2 genes including PRF1 and HTR2A were identified and predicted to be functionally damaged to their encoded proteins. In addition, the PRF1 mutation and the HTR2A mutation identified in our study were absent in 100 non-related controls, indicating that venous thromboembolism has a genetic component. The R357W mutation is located in the membrane attack complex/perforin domain of PRF1 protein, which exists in both the perforin. The steps of killing foreign or pathological antigen cells by NK cells, CD(8) (+)T cells and the membrane attack complex include membrane perforation and release of the granzyme, either of which is abnormal can lead to immune dysfunction. Conclusions: The mutations of immune related genes in familial VTE might provide new understanding of the pathogenesis of familial venous thromboembolism.",,"['Duan, Qianglin', 'Lv, Wei', 'Yang, Minjun', 'Yang, Fan', 'Zhu, Yongqiang', 'Kang, Hui', 'Song, Haoming', 'Wang, Shengyue', 'Dong, Hui', 'Wang, Lemin']",,,,
,PMC,Application of loop-mediated isothermal amplification (LAMP) assay for the rapid diagnosis of pathogenic bacteria in clinical sputum specimens of acute exacerbation of COPD (AECOPD),,PMC4509289,,,"The present study explores the application of LAMP for rapid diagnosis of pathogenic bacteria in clinical sputum specimens of AECOPD as compared with conventional sputum culturing method. 120 sputum specimens of AECOPD patients, 46 sputum specimens of healthy controls, as well as 166 serum specimens as negative controls, were evaluated by LAMP assay using primers of eight typical respiratory pathogens. No cross-reactivity was observed in these negative control species using LAMP assay. The lower detection limit of LAMP assay was approximately 10(3) copies. 25 cases (20.8%) were detected at least one positive bacteria species by conventional sputum culturing method, while 73 cases (60.8%) were tested positive in LAMP assay. Moreover, compared with sputum culture, bacterial titers results of LAMP assay were more consistent with FEV(1)/FVC value of AECOPD patients. These results indicated that the sensitivity of LAMP assay was significantly higher than that of sputum culturing method.",,"['Zhang, Wei', 'Chen, Chuanhui', 'Cui, Jian', 'Bai, Wei', 'Zhou, Jing']",,,,
,PMC,Effectiveness of contact precautions against multidrug-resistant organism transmission in acute care: a systematic review of the literature,http://dx.doi.org/10.1016/j.jhin.2015.05.003,PMC4486607,,,"Contact precautions are widely recommended to prevent multidrug-resistant organism (MDRO) transmission. However, conflicting data exist regarding their effectiveness. Prior systematic reviews examined contact precautions as part of a larger bundled approach, limiting ability to understand their effectiveness. The aim of this review was to characterize the effectiveness of contact precautions alone against transmission of any MDRO among adult acute care patients. Directed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, comprehensive searches of four electronic scientific literature databases were conducted for studies published in English from January 2004 to June 2014. Studies were included if interventional, original research, evaluating contact isolation precautions against MDRO transmission among inpatients. Searches returned 284 studies, six of which were included in the review. These studies measured four different MDROs with one study showing a reduction in transmission. Whereas studies were of high quality regarding outcome operationalization and statistical analyses, overall quality was moderate to low due to poor intervention description, population characterization and potential biases. Where compliance was measured (N = 4), it presented a threat to validity because it included select parts of the intervention, ranged from 21% to 87%, and was significantly different across study phases (N = 2). The poor quality of evidence on this topic continues to limit interpretation of these data. Hence, this conflicting body of literature does not constitute evidence for or against contact precautions. We recommend that researchers consider power calculation, compliance monitoring, non-equivalent concurrent controls when designing future studies on this topic.",,"['Cohen, C.C.', 'Cohen, B.', 'Shang, J.']",,,,
,PMC,3D Tissue-Like Assemblies: A Novel Approach to Investigate Virus-Cell Interactions,http://dx.doi.org/10.1016/j.ymeth.2015.05.010,PMC5489059,,,"Virus-host cell interactions are most commonly analyzed in cells maintained in vitro as two-dimensional tissue cultures. However, these in vitro conditions vary quite drastically from the tissues that are commonly infected in vivo. Over the years, a number of systems have been developed that allow the establishment of three-dimensional (3D) tissue structures that have properties similar to their in vivo 3D counterparts. These 3D systems have numerous applications including drug testing, maintenance of large tissue explants, monitoring migration of human lymphocytes in tissues, analysis of human organ tissue development and investigation of virus-host interactions including viral latency. Here, we describe the establishment of tissue-like assemblies for human lung and neuronal tissue that we infected with a variety of viruses including the respiratory pathogens human parainfluenza virus type 3 (PIV3), respiratory syncytial virus (RSV) and SARS corona virus (SARS-CoV) as well as the human neurotropic herpesvirus, varicella-zoster virus (VZV)",,"['Goodwin, Thomas J.', 'McCarthy, Maureen', 'Cohrs, Randall J.', 'Kaufer, Benedikt B.']",,,,
,PMC,A Single Point Mutation Creating a Furin Cleavage Site in the Spike Protein Renders Porcine Epidemic Diarrhea Coronavirus Trypsin Independent for Cell Entry and Fusion,http://dx.doi.org/10.1128/JVI.00356-15,PMC4505673,,,"The emerging porcine epidemic diarrhea virus (PEDV) requires trypsin supplementation to activate its S protein for membrane fusion and virus propagation in cell culture. By substitution of a single amino acid in the S protein, we created a recombinant PEDV with an artificial furin protease cleavage site N terminal of the putative fusion peptide (PEDV-S(FCS)). PEDV-S(FCS) exhibited trypsin-independent cell-cell fusion and was able to replicate in culture cells independently of trypsin, though to low titer.",,"['Li, Wentao', 'Wicht, Oliver', 'van Kuppeveld, Frank J. M.', 'He, Qigai', 'Rottier, Peter J. M.', 'Bosch, Berend-Jan']",,,,
,PMC,Transcriptome Profiling of the Virus-Induced Innate Immune Response in Pteropus vampyrus and Its Attenuation by Nipah Virus Interferon Antagonist Functions,http://dx.doi.org/10.1128/JVI.00302-15,PMC4505658,,,"Bats are important reservoirs for several viruses, many of which cause lethal infections in humans but have reduced pathogenicity in bats. As the innate immune response is critical for controlling viruses, the nature of this response in bats and how it may differ from that in other mammals are of great interest. Using next-generation transcriptome sequencing (mRNA-seq), we profiled the transcriptional response of Pteropus vampyrus bat kidney (PVK) cells to Newcastle disease virus (NDV), an avian paramyxovirus known to elicit a strong innate immune response in mammalian cells. The Pteropus genus is a known reservoir of Nipah virus (NiV) and Hendra virus (HeV). Analysis of the 200 to 300 regulated genes showed that genes for interferon (IFN) and antiviral pathways are highly upregulated in NDV-infected PVK cells, including genes for beta IFN, RIG-I, MDA5, ISG15, and IRF1. NDV-infected cells also upregulated several genes not previously characterized to be antiviral, such as RND1, SERTAD1, CHAC1, and MORC3. In fact, we show that MORC3 is induced by both IFN and NDV infection in PVK cells but is not induced by either stimulus in human A549 cells. In contrast to NDV infection, HeV and NiV infection of PVK cells failed to induce these innate immune response genes. Likewise, an attenuated response was observed in PVK cells infected with recombinant NDVs expressing the NiV IFN antagonist proteins V and W. This study provides the first global profile of a robust virus-induced innate immune response in bats and indicates that henipavirus IFN antagonist mechanisms are likely active in bat cells. IMPORTANCE Bats are the reservoir host for many highly pathogenic human viruses, including henipaviruses, lyssaviruses, severe acute respiratory syndrome coronavirus, and filoviruses, and many other viruses have also been isolated from bats. Viral infections are reportedly asymptomatic or heavily attenuated in bat populations. Despite their ecological importance to viral maintenance, research into their immune system and mechanisms for viral control has only recently begun. Nipah virus and Hendra virus are two paramyxoviruses associated with high mortality rates in humans and whose reservoir is the Pteropus genus of bats. Greater knowledge of the innate immune response of P. vampyrus bats to viral infection may elucidate how bats serve as a reservoir for so many viruses.",,"['Glennon, Nicole B.', 'Jabado, Omar', 'Lo, Michael K.', 'Shaw, Megan L.']",,,,
,PMC,IL-10 enhances CTL-mediated tumor rejection by inhibiting highly suppressive CD4(+) T cells and promoting CTL persistence in a murine model of plasmacytoma,http://dx.doi.org/10.1080/2162402X.2015.1014232,PMC4485799,,,"Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that regulates immune responses. IL-10 has also been shown to enhance antitumor CD8(+) T-cell responses in tumor models although the underlying mechanisms are not fully understood. In this study, we used a series of genetic mouse models and the mouse plasmacytoma J558 model to investigate this issue. J558 tumors grew significantly faster in IL-10(−/−) mice than in wild type (WT) mice, but similarly in IL-10(−/−)Rag2(−/−) and Rag2(−/−) mice. Tumors from IL-10(−/−) mice contained fewer IFN-γ-producing CD8(+) and CD4(+) T cells than tumors from WT mice. Strikingly, depletion of total CD4(+) T cells, but not CD25(+) cells, resulted in tumor eradication in IL-10(−/−) mice. Adoptive transfer studies revealed that CD4(+) T cells from IL-10(−/−) mice exhibited more potent suppression of cytotoxic T lymphocyte (CTL)-mediated tumor rejection than their WT counterparts, and IL-10–deficient tumor-infiltrating CD4(+) T cells expressed higher levels of PD-L1 and CTLA-4 inhibitory molecules. Although IL-10–deficient CD8(+) T cells are not defective in activation and initial rejection of tumors, adoptive transfer studies using IL-10–deficient P1CTL transgenic T cells that recognize the tumor rejection antigen P1A reveal that IL-10 is required for long-term persistence of CTLs and control of tumor growth. Thus, we have found that IL-10 enhances antitumor CTL responses by inhibiting highly suppressive CD4(+) T cells and promoting CTL persistence. These data have important implications for the design of immunotherapy for human cancer.",,"['Wang, Lixin', 'Liu, Jin-Qing', 'Talebian, Fatemeh', 'Liu, Zhenzhen', 'Yu, Li', 'Bai, Xue-Feng']",,,,
,PMC,Uterine artery dysfunction in pregnant ACE2 knockout mice is associated with placental hypoxia and reduced umbilical blood flow velocity,http://dx.doi.org/10.1152/ajpendo.00596.2014,PMC4490333,,,"Angiotensin-converting enzyme 2 (ACE2) knockout is associated with reduced fetal weight at late gestation; however, whether uteroplacental vascular and/or hemodynamic disturbances underlie this growth-restricted phenotype is unknown. Uterine artery reactivity and flow velocities, umbilical flow velocities, trophoblast invasion, and placental hypoxia were determined in ACE2 knockout (KO) and C57Bl/6 wild-type (WT) mice at day 14 of gestation. Although systolic blood pressure was higher in pregnant ACE2 KO vs. WT mice (102.3 ± 5.1 vs. 85.1 ± 1.9 mmHg, n = 5–6), the magnitude of difference was similar to that observed in nonpregnant ACE2 KO vs. WT mice. Maternal urinary protein excretion, serum creatinine, and kidney or heart weights were not different in ACE2 KO vs. WT. Fetal weight and pup-to-placental weight ratio were lower in ACE2 KO vs. WT mice. A higher sensitivity to Ang II [pD(2) 8.64 ± 0.04 vs. 8.5 ± 0.03 (−log EC(50))] and greater maximal contraction to phenylephrine (169.0 ± 9.0 vs. 139.0 ± 7.0% K(MAX)), were associated with lower immunostaining for Ang II receptor 2 and fibrinoid content of the uterine artery in ACE2 KO mice. Uterine artery flow velocities and trophoblast invasion were similar between study groups. In contrast, umbilical artery peak systolic velocities (60.2 ± 4.5 vs. 75.1 ± 4.5 mm/s) and the resistance index measured using VEVO 2100 ultrasound were lower in the ACE2 KO vs. WT mice. Immunostaining for pimonidazole, a marker of hypoxia, and hypoxia-inducible factor-2α were higher in the trophospongium and placental labyrinth of the ACE2 KO vs. WT. In summary, placental hypoxia and uterine artery dysfunction develop before major growth of the fetus occurs and may explain the fetal growth restricted phenotype.",,"['Yamaleyeva, Liliya M.', 'Pulgar, Victor M.', 'Lindsey, Sarah H.', 'Yamane, Larissa', 'Varagic, Jasmina', 'McGee, Carolynne', 'daSilva, Mauro', 'Lopes Bonfa, Paula', 'Gurley, Susan B.', 'Brosnihan, K. Bridget']",,,,
,PMC,Therapeutic and prevention strategies against human enterovirus 71 infection,http://dx.doi.org/10.5501/wjv.v4.i2.78,PMC4419123,,,"Human enterovirus 71 (HEV71) is the cause of hand, foot and mouth disease and associated neurological complications in children under five years of age. There has been an increase in HEV71 epidemic activity throughout the Asia-Pacific region in the past decade, and it is predicted to replace poliovirus as the extant neurotropic enterovirus of highest global public health significance. To date there is no effective antiviral treatment and no vaccine is available to prevent HEV71 infection. The increase in prevalence, virulence and geographic spread of HEV71 infection over the past decade provides increasing incentive for the development of new therapeutic and prevention strategies against this emerging viral infection. The current review focuses on the potential, advantages and disadvantages of these strategies. Since the explosion of outbreaks leading to large epidemics in China, research in natural therapeutic products has identified several groups of compounds with anti-HEV71 activities. Concurrently, the search for effective synthetic antivirals has produced promising results. Other therapeutic strategies including immunotherapy and the use of oligonucleotides have also been explored. A sound prevention strategy is crucial in order to control the spread of HEV71. To this end the ultimate goal is the rapid development, regulatory approval and widespread implementation of a safe and effective vaccine. The various forms of HEV71 vaccine designs are highlighted in this review. Given the rapid progress of research in this area, eradication of the virus is likely to be achieved.",,"Kok, Chee Choy",,,,
,PMC,A Sporozoite- and Liver Stage-expressed Tryptophan-rich Protein Plays an Auxiliary Role in Plasmodium Liver Stage Development and Is a Potential Vaccine Candidate,http://dx.doi.org/10.1074/jbc.M114.588129,PMC4528115,,,"The liver stages of the malaria parasite are clinically silent and constitute ideal targets for causal prophylactic drugs and vaccines. Cellular and molecular events responsible for liver stage development are poorly characterized. Here, we show that sporozoite, liver stage tryptophan-rich protein (SLTRiP) forms large multimers. Mice immunized with a purified recombinant SLTRiP protein gave high antibody titers in both inbred and outbred mice. Immunized mice showed highly significant levels of protection upon challenge with sporozoites and exhibited 10,000-fold fewer parasite 18S-rRNA copy numbers in their livers. The protection offered by immunization with SLTRiP came mainly from T-cells, and antibodies had little role to play despite their high titers. Immunofluorescence assays showed that SLTRiP is expressed in the sporozoite and early to late liver stages of malaria parasites. SLTRiP protein is exported to the cytosol of infected host cells during the early hours of parasite infection. Parasites deficient in SLTRiP were moderately defective in liver stage parasite development. A transcriptome profile of SLTRiP-deficient parasite-infected hepatocytes highlighted that SLTRiP interferes with multiple pathways in the host cell. We have demonstrated a role for SLTRiP in sporozoites and the liver stage of malaria parasites.",,"['Jaijyan, Dabbu Kumar', 'Singh, Himanshu', 'Singh, Agam Prasad']",,,,
,PMC,Global health security: the wider lessons from the west African Ebola virus disease epidemic,http://dx.doi.org/10.1016/S0140-6736(15)60858-3,PMC5856330,,,"The Ebola virus disease outbreak in West Africa was unprecedented in both its scale and impact. Out of this human calamity has come renewed attention to global health security—its definition, meaning, and the practical implications for programmes and policy. For example, how does a government begin to strengthen its core public health capacities, as demanded by the International Health Regulations? What counts as a global health security concern? In the context of the governance of global health, including WHO reform, it will be important to distil lessons learned from the Ebola outbreak. The Lancet invited a group of respected global health practitioners to reflect on these lessons, to explore the idea of global health security, and to offer suggestions for next steps. Their contributions describe some of the major threats to individual and collective human health, as well as the values and recommendations that should be considered to counteract such threats in the future. Many different perspectives are proposed. Their common goal is a more sustainable and resilient society for human health and wellbeing.",,"['Heymann, David L', 'Chen, Lincoln', 'Takemi, Keizo', 'Fidler, David P', 'Tappero, Jordan W', 'Thomas, Mathew J', 'Kenyon, Thomas A', 'Frieden, Thomas R', 'Yach, Derek', 'Nishtar, Sania', 'Kalache, Alex', 'Olliaro, Piero L', 'Horby, Peter', 'Torreele, Els', 'Gostin, Lawrence O', 'Ndomondo-Sigonda, Margareth', 'Carpenter, Daniel', 'Rushton, Simon', 'Lillywhite, Louis', 'Devkota, Bhimsen', 'Koser, Khalid', 'Yates, Rob', 'Dhillon, Ranu S', 'Rannan-Eliya, Ravi P']",,,,
,PMC,Multiple Sclerosis and T Lymphocytes: An Entangled Story,http://dx.doi.org/10.1007/s11481-015-9614-0,PMC5052065,,,"Multiple sclerosis (MS) is the prototypic inflammatory disease of the central nervous system (CNS) characterized by multifocal areas of demyelination, axonal damage, activation of glial cells, and immune cell infiltration. Despite intensive years of research, the etiology of this neurological disorder remains elusive. Nevertheless, the abundance of immune cells such as T lymphocytes and their products in CNS lesions of MS patients supports the notion that MS is an immune-mediated disorder. An important body of evidence gathered from MS animal models such as experimental autoimmune encephalomyelitis (EAE), points to the central contribution of CD4 T lymphocytes in disease pathogenesis. Both Th1 (producing interferon-γ) and Th17 (producing interleukin 17) CD4 T lymphocytes targeting CNS self-antigens have been implicated in MS and EAE pathobiology. Moreover, several publications suggest that CD8 T lymphocytes also participate in the development of MS lesions. The migration of activated T lymphocytes from the periphery into the CNS has been identified as a crucial step in the formation of MS lesions. Several factors promote such T cell extravasation including: molecules (e.g., cell adhesion molecules) implicated in the T cell-blood brain barrier interaction, and chemokines produced by neural cells. Finally, once in the CNS, T lymphocytes need to be reactivated by local antigen presenting cells prior to enter the parenchyma where they can initiate damage. Further investigations will be necessary to elucidate the impact of environmental factors (e.g., gut microbiota) and CNS intrinsic properties (e.g., microglial activation) on this inflammatory neurological disease.",,"['Legroux, Laurine', 'Arbour, Nathalie']",,,,
,PMC,Correlation between Serum Levels of Anti-Endothelial Cell Autoantigen and Anti-Dengue Virus Nonstructural Protein 1 Antibodies in Dengue Patients,http://dx.doi.org/10.4269/ajtmh.14-0162,PMC4426591,,,"We have previously shown that anti–dengue virus nonstructural protein 1 (anti-DENV NS1) antibodies cross-react with endothelial cells, and several autoantigens have been identified. This study shows that the antibody levels against these self-proteins are higher in sera from patients with dengue hemorrhagic fever (DHF) than those in control sera. Anti–protein disulfide isomerase (PDI) and anti–heat shock protein 60 (anti-HSP60) IgM levels correlated with both anti–endothelial cells and anti-DENV NS1 IgM titers. A cross-reactive epitope on the NS1 amino acid residues 311–330 (P311–330) had been predicted. We further found that there were higher IgM and IgG levels against P311–330 in DHF patients' sera than those in the control sera. In addition, correlations were observed between anti-PDI with anti-P311–330 IgM and IgG levels, respectively. Therefore, our results indicate that DENV NS1 P311–330 is a major epitope for cross-reactive antibodies to PDI on the endothelial cell surface, which may play an important role in DENV infection–induced autoimmunity.",,"['Cheng, Hsien-Jen', 'Luo, Yueh-Hsia', 'Wan, Shu-Wen', 'Lin, Chiou-Feng', 'Wang, Shan-Tair', 'Hung, Nguyen Thanh', 'Liu, Ching-Chuan', 'Ho, Tzong-Shiann', 'Liu, Hsiao-Sheng', 'Yeh, Trai-Ming', 'Lin, Yee-Shin']",,,,
,PMC,Novel Functions of Hendra Virus G N-Glycans and Comparisons to Nipah Virus,http://dx.doi.org/10.1128/JVI.00773-15,PMC4473544,,,"Hendra virus (HeV) and Nipah virus (NiV) are reportedly the most deadly pathogens within the Paramyxoviridae family. These two viruses bind the cellular entry receptors ephrin B2 and/or ephrin B3 via the viral attachment glycoprotein G, and the concerted efforts of G and the viral fusion glycoprotein F result in membrane fusion. Membrane fusion is essential for viral entry into host cells and for cell-cell fusion, a hallmark of the disease pathobiology. HeV G is heavily N-glycosylated, but the functions of the N-glycans remain unknown. We disrupted eight predicted N-glycosylation sites in HeV G by conservative mutations (Asn to Gln) and found that six out of eight sites were actually glycosylated (G2 to G7); one in the stalk (G2) and five in the globular head domain (G3 to G7). We then tested the roles of individual and combined HeV G N-glycan mutants and found functions in the modulation of shielding against neutralizing antibodies, intracellular transport, G-F interactions, cell-cell fusion, and viral entry. Between the highly conserved HeV and NiV G glycoproteins, similar trends in the effects of N-glycans on protein functions were observed, with differences in the levels at which some N-glycan mutants affected such functions. While the N-glycan in the stalk domain (G2) had roles that were highly conserved between HeV and NiV G, individual N-glycans in the head affected the levels of several protein functions differently. Our findings are discussed in the context of their contributions to our understanding of HeV and NiV pathogenesis and immune responses. IMPORTANCE Viral envelope glycoproteins are important for viral pathogenicity and immune evasion. N-glycan shielding is one mechanism by which immune evasion can be achieved. In paramyxoviruses, viral attachment and membrane fusion are governed by the close interaction of the attachment proteins H/HN/G and the fusion protein F. In this study, we show that the attachment glycoprotein G of Hendra virus (HeV), a deadly paramyxovirus, is N-glycosylated at six sites (G2 to G7) and that most of these sites have important roles in viral entry, cell-cell fusion, G-F interactions, G oligomerization, and immune evasion. Overall, we found that the N-glycan in the stalk domain (G2) had roles that were very conserved between HeV G and the closely related Nipah virus G, whereas individual N-glycans in the head quantitatively modulated several protein functions differently between the two viruses.",,"['Bradel-Tretheway, Birgit G.', 'Liu, Qian', 'Stone, Jacquelyn A.', 'McInally, Samantha', 'Aguilar, Hector C.']",,,,
,PMC,The Folding Unit of Phosphofructokinase-2 as Defined by the Biophysical Properties of a Monomeric Mutant,http://dx.doi.org/10.1016/j.bpj.2015.04.001,PMC4423062,,,"Escherichia coli phosphofructokinase-2 (Pfk-2) is an obligate homodimer that follows a highly cooperative three-state folding mechanism N(2) ↔ 2I ↔ 2U. The strong coupling between dissociation and unfolding is a consequence of the structural features of its interface: a bimolecular domain formed by intertwining of the small domain of each subunit into a flattened β-barrel. Although isolated monomers of E. coli Pfk-2 have been observed by modification of the environment (changes in temperature, addition of chaotropic agents), no isolated subunits in native conditions have been obtained. Based on in silico estimations of the change in free energy and the local energetic frustration upon binding, we engineered a single-point mutant to destabilize the interface of Pfk-2. This mutant, L93A, is an inactive monomer at protein concentrations below 30 μM, as determined by analytical ultracentrifugation, dynamic light scattering, size exclusion chromatography, small-angle x-ray scattering, and enzyme kinetics. Active dimer formation can be induced by increasing the protein concentration and by addition of its substrate fructose-6-phosphate. Chemical and thermal unfolding of the L93A monomer followed by circular dichroism and dynamic light scattering suggest that it unfolds noncooperatively and that the isolated subunit is partially unstructured and marginally stable. The detailed structural features of the L93A monomer and the F6P-induced dimer were ascertained by high-resolution hydrogen/deuterium exchange mass spectrometry. Our results show that the isolated subunit has overall higher solvent accessibility than the native dimer, with the exception of residues 240–309. These residues correspond to most of the β-meander module and show the same extent of deuterium uptake as the native dimer. Our results support the idea that the hydrophobic core of the isolated monomer of Pfk-2 is solvent-penetrated in native conditions and that the β-meander module is not affected by monomerizing mutations.",,"['Ramírez-Sarmiento, César\xa0A.', 'Baez, Mauricio', 'Zamora, Ricardo\xa0A.', 'Balasubramaniam, Deepa', 'Babul, Jorge', 'Komives, Elizabeth\xa0A.', 'Guixé, Victoria']",,,,
,PMC,Critical Care Medicine and Infectious Diseases: An Emerging Combined Subspecialty in the United States,http://dx.doi.org/10.1093/cid/civ360,PMC4542599,,,"The recent rise in unfilled training positions among infectious diseases (ID) fellowship programs nationwide indicates that ID is declining as a career choice among internal medicine residency graduates. Supplementing ID training with training in critical care medicine (CCM) might be a way to regenerate interest in the specialty. Hands-on patient care and higher salaries are obvious attractions. High infection prevalence and antibiotic resistance in intensive care units, expanding immunosuppressed host populations, and public health crises such as the recent Ebola outbreak underscore the potential synergy of CCM-ID training. Most intensivists receive training in pulmonary medicine and only 1% of current board-certified intensivists are trained in ID. While still small, this cohort of CCM-ID certified physicians has continued to rise over the last 2 decades. ID and CCM program leadership nationwide must recognize these trends and the merits of the CCM-ID combination to facilitate creation of formal dual-training opportunities.",,"['Kadri, Sameer S.', 'Rhee, Chanu', 'Fortna, Gregory S.', ""O'Grady, Naomi P.""]",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00894-15,PMC4442423,,,,,,,,,
,PMC,ACTIVATION OF THE NEUROPROTECTIVE ANGIOTENSIN CONVERTING ENZYME 2 IN RAT ISCHEMIC STROKE,http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.05185,PMC4465873,,,"The angiotensin converting enzyme 2/angiotensin-(1-7)/Mas axis represents a promising target for inducing stroke neuroprotection. Here, explored stroke-induced changes in expression and activity of endogenous angiotensin converting enzyme 2 and other system components in Sprague Dawley rats. To evaluate the clinical feasibility of treatments that target this axis and that may act in synergy with stroke-induced changes, we also tested the neuroprotective effects of diminazene aceturate, an angiotensin converting enzyme 2 activator, administered systemically post-stroke. Amongst rats that underwent experimental endothelin-1-induced ischemic stroke, angiotensin converting enzyme 2 activity in the cerebral cortex and striatum increased in the 24 hours after stroke. Serum angiotensin converting enzyme 2 activity was decreased within 4h post stroke, but rebounded to reach higher than baseline levels 3d post-stroke. Treatment following stroke with systemically-applied diminazene resulted in decreased infarct volume and improved neurological function without apparent increases in cerebral blood flow. Central infusion of A-779, a Mas receptor antagonist, resulted in larger infarct volumes in diminazene-treated rats, and central infusion of the angiotensin converting enzyme 2 inhibitor MLN-4760 alone worsened neurological function. The dynamic alterations of the protective angiotensin converting enzyme 2 pathway following stroke suggest that it may be a favorable therapeutic target. Indeed, significant neuroprotection resulted from post-stroke angiotensin converting enzyme 2 activation, likely via Mas signaling in a blood flow-independent manner. Our findings suggest that stroke therapeutics that target the angiotensin converting enzyme 2/angiotensin-(1-7)/Mas axis may interact cooperatively with endogenous stroke-induced changes, lending promise to their further study as neuroprotective agents.",,"['Bennion, Douglas M.', 'Haltigan, Emily', 'Irwin, Alexander J.', 'Donnangelo, Lauren L.', 'Regenhardt, Robert W.', 'Pioquinto, David', 'Purich, Daniel L.', 'Sumners, Colin']",,,,
,PMC,The Role of Surfactant in Lung Disease and Host Defense against Pulmonary Infections,http://dx.doi.org/10.1513/AnnalsATS.201411-507FR,PMC4418337,,,"Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing. Surfactant is enriched with a relatively unique phospholipid, termed dipalmitoylphosphatidylcholine, and four surfactant-associated proteins, SP-A, SP-B, SP-C, and SP-D. The hydrophobic proteins, SP-B and SP-C, together with dipalmitoylphosphatidylcholine, confer surface tension–lowering properties to the material. The more hydrophilic surfactant components, SP-A and SP-D, participate in pulmonary host defense and modify immune responses. Specifically, SP-A and SP-D bind and partake in the clearance of a variety of bacterial, fungal, and viral pathogens and can dampen antigen-induced immune function of effector cells. Emerging data also show immunosuppressive actions of some surfactant-associated lipids, such as phosphatidylglycerol. Conversely, microbial pathogens in preclinical models impair surfactant synthesis and secretion, and microbial proteinases degrade surfactant-associated proteins. Deficiencies of surfactant components are classically observed in the neonatal respiratory distress syndrome, where surfactant replacement therapies have been the mainstay of treatment. However, functional or compositional deficiencies of surfactant are also observed in a variety of acute and chronic lung disorders. Increased surfactant is seen in pulmonary alveolar proteinosis, a disorder characterized by a functional deficiency of the granulocyte-macrophage colony-stimulating factor receptor or development of granulocyte-macrophage colony-stimulating factor antibodies. Genetic polymorphisms of some surfactant proteins such as SP-C are linked to interstitial pulmonary fibrosis. Here, we briefly review the composition, antimicrobial properties, and relevance of pulmonary surfactant to lung disorders and present its therapeutic implications.",,"['Han, SeungHye', 'Mallampalli, Rama K.']",,,,
,PMC,Toward a Mechanistic Understanding of Environmentally Forced Zoonotic Disease Emergence: Sin Nombre Hantavirus,http://dx.doi.org/10.1093/biosci/biv047,PMC4776718,,,"Understanding the environmental drivers of zoonotic reservoir and human interactions is crucial to understanding disease risk, but these drivers are poorly predicted. We propose a mechanistic understanding of human–reservoir interactions, using hantavirus pulmonary syndrome as a case study. Crucial processes underpinning the disease's incidence remain poorly studied, including the connectivity among natural and peridomestic deer mouse host activity, virus transmission, and human exposure. We found that disease cases were greatest in arid states and declined exponentially with increasing precipitation. Within arid environments, relatively rare climatic conditions (e.g., El Niño) are associated with increased rainfall and reservoir abundance, producing more frequent virus transmission and host dispersal. We suggest that deer mice increase their occupancy of peridomestic structures during spring–summer, amplifying intraspecific transmission and human infection risk. Disease incidence in arid states may increase with predicted climatic changes. Mechanistic approaches incorporating reservoir behavior, reservoir–human interactions, and pathogen spillover could enhance our understanding of global hantavirus ecology, with applications to other directly transmitted zoonoses.",,"['Carver, Scott', 'Mills, James N.', 'Parmenter, Cheryl A.', 'Parmenter, Robert R.', 'Richardson, Kyle S.', 'Harris, Rachel L.', 'Douglass, Richard J.', 'Kuenzi, Amy J.', 'Luis, Angela D.']",,,,
,PMC,History of Passive Antibody Administration for Prevention and Treatment of Infectious Diseases,http://dx.doi.org/10.1097/COH.0000000000000154,PMC4437582,,,"PURPOSE OF THE REVIEW: We describe the history of passive immunization to provide context for the series of articles to follow. The history of passive immunization with antibodies to prevent or treat infectious diseases is a story of different eras. There was an extraordinary era of discovery and clinical implementation before the chemical nature of antibodies was even known. This empirical process provided the resources and reagents used to describe and characterize humoral immunity, better define the chemical properties and structure of antibodies, and extend the clinical use of immunoglobulin products to treat or prevent multiple viral and bacterial diseases over the ensuing several decades. The next distinct era came with the discovery of processes to produce monoclonal antibodies (mAb), and development of more specific therapies. Interestingly, mAb technology resulted in many products to treat autoimmune and allergic diseases, but only one common infectious disease, respiratory syncytial virus, and only in a restricted population of high-risk infants. RECENT FINDINGS: The current era began with a series of publications in 2008 demonstrating processes for rapidly producing human mAbs. SUMMARY: This technology combined with new sequencing technology, advances in structural biology, atomic-level molecular design, and increased capacity for synthetic biology, promises new opportunities to apply passive immunization to the prevention and treatment of infectious diseases.",,"['Graham, Barney S.', 'Ambrosino, Donna M.']",,,,
,PMC,Growth and Quantification of MERS-CoV Infection,http://dx.doi.org/10.1002/9780471729259.mc15e02s37,PMC4735735,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging highly pathogenic respiratory virus. Although MERS-CoV only emerged in 2012, we and others have developed assays to grow and quantify infectious MERS-CoV and RNA products of replication in vitro. MERS-CoV is able to infect a range of cell types, but replicates to high titers in Vero E6 cells. Protocols for the propagation and quantification of MERS-CoV are presented.",,"['Coleman, Christopher M.', 'Frieman, Matthew B.']",,,,
,PMC,Enucleation for Treating Rodent Ocular Disease,,PMC4460947,,,"Our standard of care for rodent corneal lesions previously included treatment of the primary lesion, application of topical NSAIDs, and systemic NSAIDs in severe cases. When intensive medical management was unsuccessful, animals were euthanized, leading to premature loss of valuable genetically modified animals and those on long-term studies. We investigated enucleation surgery as a treatment for 15 cases of rodent corneal disease that did not respond to medical management. Enucleation was performed under isoflurane anesthesia and involved removal of the globe, extensive hemostasis, and packing the orbital space with absorbable gelatin sponge. The lid margins were closed by tarsorrhaphy and tissue glue. Analgesia was provided by using buprenorphine preoperatively and carprofen chew tabs postoperatively. To date, we have a 100% success rate with this procedure (n = 20; 15 clinically affected rodents [2 rats, 13 mice], 5 healthy controls), which included a 60-d follow-up period. The single complication involved dehiscence of the tarsorrhaphy site and was repaired by trimming the lid margins to provide fresh tissue for closure. Histologic examination at both 1 and 3 mo after surgery revealed no evidence of infection of the enucleation site. Enucleation in rodents is a straightforward procedure that represents a refinement to our current standard of care for rodents, does not cause significant inflammation of remaining periocular structures, and has reduced the number of animals euthanized prior to study endpoint because of severe ocular lesions.",,"['Wilding, Laura A', 'Uchihashi, Mayu', 'Bergin, Ingrid L', 'Nowland, Megan H']",,,,
,PMC,CSAX: Characterizing Systematic Anomalies in eXpression Data,http://dx.doi.org/10.1089/cmb.2014.0155,PMC4424968,,,"Methods for translating gene expression signatures into clinically relevant information have typically relied upon having many samples from patients with similar molecular phenotypes. Here, we address the question of what can be done when it is relatively easy to obtain healthy patient samples, but when abnormalities corresponding to disease states may be rare and one-of-a-kind. The associated computational challenge, anomaly detection, is a well-studied machine-learning problem. However, due to the dimensionality and variability of expression data, existing methods based on feature space analysis or individual anomalously expressed genes are insufficient. We present a novel approach, CSAX, that identifies pathways in an individual sample in which the normal expression relationships are disrupted. To evaluate our approach, we have compiled and released a compendium of public expression data sets, reformulated to create a test bed for anomaly detection. We demonstrate the accuracy of CSAX on the data sets in our compendium, compare it to other leading methods, and show that CSAX aids in both identifying anomalies and explaining their underlying biology. We describe an approach to characterizing the difficulty of specific expression anomaly detection tasks. We then illustrate CSAX's value in two developmental case studies. Confirming prior hypotheses, CSAX highlights disruption of platelet activation pathways in a neonate with retinopathy of prematurity and identifies, for the first time, dysregulated oxidative stress response in second trimester amniotic fluid of fetuses with obese mothers. Our approach provides an important step toward identification of individual disease patterns in the era of precision medicine.",,"['Noto, Keith', 'Majidi, Saeed', 'Edlow, Andrea G.', 'Wick, Heather C.', 'Bianchi, Diana W.', 'Slonim, Donna K.']",,,,
,PMC,Assessment of the awareness level of dental students toward Middle East Respiratory Syndrome-coronavirus,http://dx.doi.org/10.4103/2231-0762.159951,PMC4515797,26236674,CC BY-NC-SA,"BACKGROUND: Infection prevention and control measures are critical to prevent the possible spread of Middle East Respiratory Syndrome-coronavirus (MERS-CoV) in healthcare facilities. Therefore, healthcare workers should be aware of all procedures concerning prevention of and protection from MERS-CoV. OBJECTIVE: The aim of this study is to improve the knowledge of the dental students and evaluate their awareness about MERS-CoV. MATERIALS AND METHODS: A questionnaire was made according to MOH information and 200 dental students (Al-Farabi Colleges, Jeddah) were interviewed to evaluate their knowledge about MERS-CoV. RESULTS: More than half of the dental students (54%) interviewed had good knowledge about the etiology, symptoms, and treatment of MERS-CoV. Measurements for infection control and protection were also known (79%). The sources of information for the students were: college (27%), MOH (25%), media (24%), and social community (23%), while 17% of the students interviewed had no idea about it. CONCLUSION: Dental students had good knowledge about MERS-CoV. However, more information still must be provided by MOH and college for the medical staff.",2015 May-Jun,"['Kharma, Mohamed Yasser', 'Alalwani, Mohamad Sadek', 'Amer, Manal Fouad', 'Tarakji, Bassel', 'Aws, Ghassan']",J Int Soc Prev Community Dent,,,
,PMC,Transcriptional Regulation of CXCL5 in HIV-1-Infected Macrophages and Its Functional Consequences on CNS Pathology,http://dx.doi.org/10.1089/jir.2014.0135,PMC4426304,,,"Human immunodeficiency virus-1 (HIV-1)-infected monocytes/macrophages and microglia release increased levels of proinflammatory cytokines and chemokines, including ELR+ (containing glutamic acid–leucine–arginine motif) chemokines. To investigate the role of HIV-1 infection on chemokine regulation, monocyte-derived macrophages (MDMs) from normal donors were infected with HIV-1 and the expression of chemokines and their downstream biological functions were evaluated. Among the tested chemokines, CXCL5 was upregulated significantly both at the mRNA and protein level in the HIV-1-infected MDMs compared with mock-infected cultures. Upregulation of CXCL5 in the HIV-1-infected MDMs is, in part, regulated by increased interleukin-1β (IL-1β) production and phosphorylation of ERK1/2. Functional analyses indicate that HIV-1-induced overexpression of CXCL5 has enhanced the ability to attract neutrophils, as observed by chemotaxis assay. However, exposure of NT2, SH-SY5Y cells, and primary neurons to HIV-1-infected MDM supernatants resulted in cell death that was not rescued by anti-CXCL5 antibody suggesting that CXCL5 does not have direct effect on neuronal death. Together, these results suggest that the increased level of CXCL5 in tissue compartments, including the central nervous system of HIV-1-infected individuals might alter the inflammatory response through the infiltration of neutrophils into tissue compartment, thus causing secondary effects on resident cells.",,"['Guha, Debjani', 'Klamar, Cynthia R.', 'Reinhart, Todd', 'Ayyavoo, Velpandi']",,,,
,PMC,Eliciting Disease Data from Wikipedia Articles,,PMC5511739,,,"Traditional disease surveillance systems suffer from several disadvantages, including reporting lags and antiquated technology, that have caused a movement towards internet-based disease surveillance systems. Internet systems are particularly attractive for disease outbreaks because they can provide data in near real-time and can be verified by individuals around the globe. However, most existing systems have focused on disease monitoring and do not provide a data repository for policy makers or researchers. In order to fill this gap, we analyzed Wikipedia article content. We demonstrate how a named-entity recognizer can be trained to tag case counts, death counts, and hospitalization counts in the article narrative that achieves an F1 score of 0.753. We also show, using the 2014 West African Ebola virus disease epidemic article as a case study, that there are detailed time series data that are consistently updated that closely align with ground truth data. We argue that Wikipedia can be used to create the first community-driven open-source emerging disease detection, monitoring, and repository system.",,"['Fairchild, Geoffrey', 'Del Valle, Sara Y.', 'De Silva, Lalindra', 'Segre, Alberto M.']",,,,
,PMC,Zinc for the common cold,http://dx.doi.org/10.1002/14651858.CD001364.pub5,PMC6457799,,,"BACKGROUND: The common cold is one of the most widespread illnesses and is a leading cause of visits to the doctor and absence from school and work. Trials conducted in high‐income countries since 1984 investigating the role of zinc for the common cold symptoms have had mixed results. Inadequate treatment masking and reduced bioavailability of zinc from some formulations have been cited as influencing results. OBJECTIVES: To assess whether zinc (irrespective of the zinc salt or formulation used) is efficacious in reducing the incidence, severity and duration of common cold symptoms. In addition, we aimed to identify potential sources of heterogeneity in results obtained and to assess their clinical significance. SEARCH METHODS: In this updated review, we searched CENTRAL (2012, Issue 12), MEDLINE (1966 to January week 2, 2013), EMBASE (1974 to January 2013), CINAHL (1981 to January 2013), Web of Science (1985 to January 2013), LILACS (1982 to January 2013), WHO ICTRP and clinicaltrials.gov. SELECTION CRITERIA: Randomised, double‐blind, placebo‐controlled trials using zinc for at least five consecutive days to treat, or for at least five months to prevent the common cold. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. MAIN RESULTS: Five trials were identified in the updated searches in January 2013 and two of them did not meet our inclusion criteria. We included 16 therapeutic trials (1387 participants) and two preventive trials (394 participants). Intake of zinc was associated with a significant reduction in the duration (days) (mean difference (MD) ‐1.03, 95% confidence interval (CI) ‐1.72 to ‐0.34) (P = 0.003) (I(2) statistic = 89%) but not the severity of common cold symptoms (MD ‐1.06, 95% CI ‐2.36 to 0.23) (P = 0.11) (I(2) statistic = 84%). The proportion of participants who were symptomatic after seven days of treatment was significantly smaller (odds ratio (OR) 0.45, 95% CI 0.20 to 1.00) (P = 0.05) than those in the control, (I(2 )statistic = 75%). The incidence rate ratio (IRR) of developing a cold (IRR 0.64, 95% CI 0.47 to 0.88) (P = 0.006) (I(2) statistic = 88%), school absence (P = 0.0003) and prescription of antibiotics (P < 0.00001) was lower in the zinc group. Overall adverse events (OR 1.58, 95% CI 1.19 to 2.09) (P = 0.002), bad taste (OR 2.31, 95% CI 1.71 to 3.11) (P < 0.00001) and nausea (OR 2.15, 95% CI 1.44 to 3.23) (P = 0.002) were higher in the zinc group. The very high heterogeneity means that the averaged estimates must be viewed with caution. AUTHORS' CONCLUSIONS: Zinc administered within 24 hours of onset of symptoms reduces the duration of common cold symptoms in healthy people but some caution is needed due to the heterogeneity of the data. As the zinc lozenges formulation has been widely studied and there is a significant reduction in the duration of cold at a dose of ≥ 75 mg/day, for those considering using zinc it would be best to use it at this dose throughout the cold. Regarding prophylactic zinc supplementation, currently no firm recommendation can be made because of insufficient data. When using zinc lozenges (not as syrup or tablets) the likely benefit has to be balanced against side effects, notably a bad taste and nausea.",,"['Singh, Meenu', 'Das, Rashmi R']",,,,
,PMC,Anti-inflammatory functions of Houttuynia cordata Thunb. and its compounds: A perspective on its potential role in rheumatoid arthritis,http://dx.doi.org/10.3892/etm.2015.2467,PMC4487049,,,"The aim of this review was to take a look at the anti-inflammatory functions of Houttuynia cordata Thunb. (HCT) that have been illustrated in the literature and to explore new fields in which HCT could be used in the future. The use of HCT has been described in broad inflammatory domains, where it has exhibited a variety of activities, including antiviral, antibacterial, antiparasitic and immunostimulant activity, with high efficiency, mild features and definite therapeutic effects. The numerous anti-inflammatory functions of HCT have demonstrated that HCT has wide application prospects. New uses of HCT and the full extent of its utilization await further investigation. The basic pathological change of rheumatoid arthritis (RA) is synovial proliferation which leads to joint destruction in the long-term. There are types of drugs that have been used clinically for patients with RA, however, due to their side-effects or high prices their broad usage is limited. A safe and low-cost drug is urgently required to be developed for the clinical usage of patients with RA. Thus, HCT has the potential to be a good candidate in the treatment of rheumatoid arthritis.",,"['LI, JUN', 'ZHAO, FUTAO']",,,,
,PMC,Highly Pathogenic New World and Old World Human Arenaviruses Induce Distinct Interferon Responses in Human Cells,http://dx.doi.org/10.1128/JVI.00526-15,PMC4473569,,,"The arenavirus family includes several important pathogens that cause severe and sometimes fatal diseases in humans. The highly pathogenic Old World (OW) arenavirus Lassa fever virus (LASV) is the causative agent of Lassa fever (LF) disease in humans. LASV infections in severe cases are generally immunosuppressive without stimulating interferon (IFN) induction, a proinflammatory response, or T cell activation. However, the host innate immune responses to highly pathogenic New World (NW) arenaviruses are not well understood. We have previously shown that the highly pathogenic NW arenavirus, Junin virus (JUNV), induced an IFN response in human A549 cells. Here, we report that Machupo virus (MACV), another highly pathogenic NW arenavirus, also induces an IFN response. Importantly, both pathogenic NW arenaviruses, in contrast to the OW highly pathogenic arenavirus LASV, readily elicited an IFN response in human primary dendritic cells and A549 cells. Coinfection experiments revealed that LASV could potently inhibit MACV-activated IFN responses even at 6 h after MACV infection, while the replication levels of MACV and LASV were not affected by virus coinfection. Our results clearly demonstrated that although all viruses studied herein are highly pathogenic to humans, the host IFN responses toward infections with the NW arenaviruses JUNV and MACV are quite different from responses to infections with the OW arenavirus LASV, a discovery that needs to be further investigated in relevant animal models. This finding might help us better understand various interplays between the host immune system and highly pathogenic arenaviruses as well as distinct mechanisms underlying viral pathogenesis. IMPORTANCE Infections of humans with the highly pathogenic OW LASV are accompanied by potent suppression of interferon or proinflammatory cytokine production. In contrast, infections with the highly pathogenic NW arenavirus JUNV are associated with high levels of IFNs and cytokines in severe and fatal cases. Arenaviruses initially target macrophages and dendritic cells, which are potent IFN/cytokine-producers. In human macrophages, JUNV reportedly does not trigger IFN responses. We here demonstrated that JUNV activated IFN responses in human dendritic cells. MACV, another highly pathogenic NW arenavirus, also activated IFN responses. LASV did not induce detectable IFN responses, in spite of higher replication levels, and blocked the MACV-triggered IFN response in a coinfection assay. Although these viruses are highly pathogenic to humans, our study highlights distinct innate immune responses to infections with the NW arenaviruses JUNV and MACV and to infection with the OW arenavirus LASV and provides important insights into the virus-host interaction and pathogenesis.",,"['Huang, Cheng', 'Kolokoltsova, Olga A.', 'Yun, Nadezhda E.', 'Seregin, Alexey V.', 'Ronca, Shannon', 'Koma, Takaaki', 'Paessler, Slobodan']",,,,
,PMC,Human Cytokinome Analysis for Interferon Response,http://dx.doi.org/10.1128/JVI.03729-14,PMC4473565,,,"Cytokines are a group of small secreted proteins that mediate a diverse range of immune and nonimmune responses to inflammatory and microbial stimuli. Only a few of these cytokines mount an antiviral response, including type I, II, and III interferons (IFNs). During viral infections and under inflammatory conditions, a number of cytokines and chemokines are coproduced with IFN; however, no systematic study exists on the interactions of the cytokine repertoire with the IFN response. Here, we performed the largest cytokine and chemokine screen (the human cytokinome, with >240 members) to investigate their modulation of type I and type II IFN responses in a cell line model. We evaluated the cytokine activities in both IFN-stimulated response element (ISRE) and IFN-γ activation sequence (GAS) reporter systems. Several cytokine clusters that augment either or both ISRE- and GAS-mediated responses to IFNs were derived from the screen. We identified novel modulators of IFN response—betacellulin (BTC), interleukin 11 (IL-11), and IL-17F—that caused time-dependent induction of the IFN response. The ability to induce endogenous IFN-β and IFN-stimulated genes varies among these cytokines and was largely dependent on Stat1, as assessed by Stat1 mutant fibroblasts. Certain cytokines appear to augment the IFN-β response through the NF-κB pathway. The novel IFN-like cytokines augmented the antiviral activity of IFN-α against several RNA viruses, including encephalomyocarditis virus, vesicular stomatitis virus, and influenza virus, in susceptible cell lines. Overall, the study represents a large-scale analysis of cytokines for enhancing the IFN response and identified cytokines capable of enhancing Stat1, IFN-induced gene expression, and antiviral activities. IMPORTANCE Innate immunity to viruses is an early defense system to ward off viruses. One mediator is interferon (IFN), which activates a cascade of biochemical events that aim to control the virus life cycle. In our work, we examined more than 200 cytokines, soluble mediators produced within the body as a result of infection, for the ability to enhance IFN action. We identified enhanced interactions with specific IFNs and cytokines. We also revealed that betacellulin, IL-17, and IL-11 cytokines have the novel property of enhancing the antiviral action of IFN against several viruses. These results demonstrate that the human genome codes for previously unknown proteins with unrelated functions that can augment the innate immunity to viruses. Knowing these interactions not only helps our understanding of immunity to viruses and emerging diseases, but can also lead to devising possible new therapeutics by enhancing the mediator of antiviral action itself, IFN.",,"['Al-Yahya, Suhad', 'Mahmoud, Linah', 'Al-Zoghaibi, Fahad', 'Al-Tuhami, Abdullah', 'Amer, Haithem', 'Almajhdi, Fahad N.', 'Polyak, Stephen J.', 'Khabar, Khalid S. A.']",,,,
,PMC,Human Coronavirus HKU1 Spike Protein Uses O-Acetylated Sialic Acid as an Attachment Receptor Determinant and Employs Hemagglutinin-Esterase Protein as a Receptor-Destroying Enzyme,http://dx.doi.org/10.1128/JVI.00854-15,PMC4473545,,,"Human coronavirus (hCoV) HKU1 is one of six hCoVs identified to date and the only one with an unidentified cellular receptor. hCoV-HKU1 encodes a hemagglutinin-esterase (HE) protein that is unique to the group a betacoronaviruses (group 2a). The function of HKU1-HE remains largely undetermined. In this study, we examined binding of the S1 domain of hCoV-HKU1 spike to a panel of cells and found that the S1 could specifically bind on the cell surface of a human rhabdomyosarcoma cell line, RD. Pretreatment of RD cells with neuraminidase (NA) and trypsin greatly reduced the binding, suggesting that the binding was mediated by sialic acids on glycoproteins. However, unlike other group 2a CoVs, e.g., hCoV-OC43, for which 9-O-acetylated sialic acid (9-O-Ac-Sia) serves as a receptor determinant, HKU1-S1 bound with neither 9-O-Ac-Sia-containing glycoprotein(s) nor rat and mouse erythrocytes. Nonetheless, the HKU1-HE was similar to OC43-HE, also possessed sialate-O-acetylesterase activity, and acted as a receptor-destroying enzyme (RDE) capable of eliminating the binding of HKU1-S1 to RD cells, whereas the O-acetylesterase-inactive HKU1-HE mutant lost this capacity. Using primary human ciliated airway epithelial (HAE) cell cultures, the only in vitro replication model for hCoV-HKU1 infection, we confirmed that pretreatment of HAE cells with HE but not the enzymatically inactive mutant blocked hCoV-HKU1 infection. These results demonstrate that hCoV-HKU1 exploits O-Ac-Sia as a cellular attachment receptor determinant to initiate the infection of host cells and that its HE protein possesses the corresponding sialate-O-acetylesterase RDE activity. IMPORTANCE Human coronaviruses (hCoV) are important human respiratory pathogens. Among the six hCoVs identified to date, only hCoV-HKU1 has no defined cellular receptor. It is also unclear whether hemagglutinin-esterase (HE) protein plays a role in viral entry. In this study, we found that, similarly to other members of the group 2a CoVs, sialic acid moieties on glycoproteins are critical receptor determinants for the hCoV-HKU1 infection. Interestingly, the virus seems to employ a type of sialic acid different from those employed by other group 2a CoVs. In addition, we determined that the HKU1-HE protein is an O-acetylesterase and acts as a receptor-destroying enzyme (RDE) for hCoV-HKU1. This is the first study to demonstrate that hCoV-HKU1 uses certain types of O-acetylated sialic acid residues on glycoproteins to initiate the infection of host cells and that the HKU1-HE protein possesses sialate-O-acetylesterase RDE activity.",,"['Huang, Xingchuan', 'Dong, Wenjuan', 'Milewska, Aleksandra', 'Golda, Anna', 'Qi, Yonghe', 'Zhu, Quan K.', 'Marasco, Wayne A.', 'Baric, Ralph S.', 'Sims, Amy C.', 'Pyrc, Krzysztof', 'Li, Wenhui', 'Sui, Jianhua']",,,,
,PMC,Cathepsin L Mediates the Degradation of Novel APP C-Terminal Fragments,http://dx.doi.org/10.1021/acs.biochem.5b00329,PMC4521409,,,"Alzheimer's disease (AD) is characterized by the deposition of amyloid β (Aβ), a peptide generated from proteolytic processing of its precursor, amyloid precursor protein (APP). Canonical APP proteolysis occurs via α-, β-, and γ-secretases. APP is also actively degraded by protein degradation systems. By pharmacologically inhibiting protein degradation with ALLN, we observed an accumulation of several novel APP C-terminal fragments (CTFs). The two major novel CTFs migrated around 15 and 25 kDa and can be observed across multiple cell types. The process was independent of cytotoxicity or protein synthesis. We further determine that the accumulation of the novel CTFs is not mediated by proteasome or calpain inhibition, but by cathepsin L inhibition. Moreover, these novel CTFs are not generated by an increased amount of BACE. Here, we name the CTF of 25 kDa as η-CTF (eta-CTF). Our data suggest that under physiological conditions, a subset of APP undergoes alternative processing and the intermediate products, the 15 kDa CTFs, and the η-CTFs aret rapidly degraded and/or processed via the protein degradation machinery, specifically, cathepsin L.",,"['Wang, Haizhi', 'Sang, Nianli', 'Zhang, Can', 'Raghupathi, Ramesh', 'Tanzi, Rudolph E.', 'Saunders, Aleister']",,,,
,PMC,Apolipoprotein D Internalization Is a Basigin-dependent Mechanism,http://dx.doi.org/10.1074/jbc.M115.644302,PMC4481210,,,"Apolipoprotein D (apoD), a member of the lipocalin family, is a 29-kDa secreted glycoprotein that binds and transports small lipophilic molecules. Expressed in several tissues, apoD is up-regulated under different stress stimuli and in a variety of pathologies. Numerous studies have revealed that overexpression of apoD led to neuroprotection in various mouse models of acute stress and neurodegeneration. This multifunctional protein is internalized in several cells types, but the specific internalization mechanism remains unknown. In this study, we demonstrate that the internalization of apoD involves a specific cell surface receptor in 293T cells, identified as the transmembrane glycoprotein basigin (BSG, CD147); more particularly, its low glycosylated form. Our results show that internalized apoD colocalizes with BSG into vesicular compartments. Down-regulation of BSG disrupted the internalization of apoD in cells. In contrast, overexpression of basigin in SH-5YSY cells, which poorly express BSG, restored the uptake of apoD. Cyclophilin A, a known ligand of BSG, competitively reduced apoD internalization, confirming that BSG is a key player in the apoD internalization process. In summary, our results demonstrate that basigin is very likely the apoD receptor and provide additional clues on the mechanisms involved in apoD-mediated functions, including neuroprotection.",,"['Najyb, Ouafa', 'Brissette, Louise', 'Rassart, Eric']",,,,
,PMC,Structures of the Middle East respiratory syndrome coronavirus 3C-like protease reveal insights into substrate specificity,http://dx.doi.org/10.1107/S1399004715003521,PMC4427198,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus that causes severe respiratory illness accompanied by multi-organ dysfunction, resulting in a case fatality rate of approximately 40%. As found in other coronaviruses, the majority of the positive-stranded RNA MERS-CoV genome is translated into two polyproteins, one created by a ribosomal frameshift, that are cleaved at three sites by a papain-like protease and at 11 sites by a 3C-like protease (3CL(pro)). Since 3CL(pro) is essential for viral replication, it is a leading candidate for therapeutic intervention. To accelerate the development of 3CL(pro) inhibitors, three crystal structures of a catalytically inactive variant (C148A) of the MERS-CoV 3CL(pro) enzyme were determined. The aim was to co-crystallize the inactive enzyme with a peptide substrate. Fortuitously, however, in two of the structures the C-terminus of one protomer is bound in the active site of a neighboring molecule, providing a snapshot of an enzyme–product complex. In the third structure, two of the three protomers in the asymmetric unit form a homodimer similar to that of SARS-CoV 3CL(pro); however, the third protomer adopts a radically different conformation that is likely to correspond to a crystallographic monomer, indicative of substantial structural plasticity in the enzyme. The results presented here provide a foundation for the structure-based design of small-molecule inhibitors of the MERS-CoV 3CL(pro) enzyme.",,"['Needle, Danielle', 'Lountos, George T.', 'Waugh, David S.']",,,,
,PMC,Serum Procalcitonin Measurement and Viral Testing to Guide Antibiotic Use for Respiratory Infections in Hospitalized Adults: A Randomized Controlled Trial,http://dx.doi.org/10.1093/infdis/jiv252,PMC4633755,,,"Background. Viral lower respiratory tract illness (LRTI) frequently causes adult hospitalization and is linked to antibiotic overuse. European studies suggest that the serum procalcitonin (PCT) level may be used to guide antibiotic therapy. We conducted a trial assessing the feasibility of using PCT algorithms with viral testing to guide antibiotic use in a US hospital. Methods. Three hundred patients hospitalized with nonpneumonic LRTI during October 2013–April 2014 were randomly assigned at a ratio of 1:1 to receive standard care or PCT-guided care and viral PCR testing. The primary outcome was antibiotic exposure, and safety was assessed at 1 and 3 months. Results. Among the 151 patients in the intervention group, viruses were identified in 42% (63), and 83% (126) had PCT values of <0.25 µg/mL. There were no significant differences in antibiotic use or adverse events between intervention patients and those in the nonintervention group. Subgroup analyses revealed fewer subjects with positive results of viral testing and low PCT values who were discharged receiving antibiotics (20% vs 45%; P = .002) and shorter antibiotic durations among algorithm-adherent intervention patients versus nonintervention patients (2.0 vs 4.0 days; P = .004). Compared with historical controls (from 2008–2011), antibiotic duration in nonintervention patients decreased by 2 days (6.0 vs 4.0 days; P < .001), suggesting a study effect. Conclusions. Although antibiotic use was similar in the 2 arms, subgroup analyses of intervention patients suggest that physicians responded to viral and biomarker data. These data can inform the design of future US studies. Clinical Trials Registration. NCT01907659.",,"['Branche, Angela R.', 'Walsh, Edward E.', 'Vargas, Roberto', 'Hulbert, Barbara', 'Formica, Maria A.', 'Baran, Andrea', 'Peterson, Derick R.', 'Falsey, Ann R.']",,,,
,PMC,Nonneutralizing Antibodies Induced by the HIV-1 gp41 NHR Domain Gain Neutralizing Activity in the Presence of the HIV Fusion Inhibitor Enfuvirtide: a Potential Therapeutic Vaccine Strategy,http://dx.doi.org/10.1128/JVI.00791-15,PMC4468469,,,"A key barrier against developing preventive and therapeutic human immunodeficiency virus (HIV) vaccines is the inability of viral envelope glycoproteins to elicit broad and potent neutralizing antibodies. However, in the presence of fusion inhibitor enfuvirtide, we show that the nonneutralizing antibodies induced by the HIV type 1 (HIV-1) gp41 N-terminal heptad repeat (NHR) domain (N63) exhibit potent and broad neutralizing activity against laboratory-adapted HIV-1 strains, including the drug-resistant variants, and primary HIV-1 isolates with different subtypes, suggesting the potential of developing gp41-targeted HIV therapeutic vaccines.",,"['Wang, Qian', 'Bi, Wenwen', 'Zhu, Xiaojie', 'Li, Haoyang', 'Qi, Qianqian', 'Yu, Fei', 'Lu, Lu', 'Jiang, Shibo']",,,,
,PMC,Systemic and mucosal immunity in mice elicited by a single immunization with human adenovirus type 5 or 41 vector-based vaccines carrying the spike protein of Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1111/imm.12462,PMC4515128,,,"An ideal vaccine against mucosal pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV) should confer sustained, protective immunity at both systemic and mucosal levels. Here, we evaluated the in vivo systemic and mucosal antigen-specific immune responses induced by a single intramuscular or intragastric administration of recombinant adenoviral type 5 (Ad5) or type 41 (Ad41) -based vaccines expressing the MERS-CoV spike (S) protein. Intragastric administration of either Ad5-S or Ad41-S induced antigen-specific IgG and neutralizing antibody in serum; however, antigen-specific T-cell responses were not detected. In contrast, after a single intramuscular dose of Ad5-S or Ad41-S, functional antigen-specific T-cell responses were elicited in the spleen and pulmonary lymphocytes of the mice, which persisted for several months. Both rAd-based vaccines administered intramuscularly induced systemic humoral immune responses (neutralizing IgG antibodies). Our results show that a single dose of Ad5-S- or Ad41-S-based vaccines represents an appealing strategy for the control of MERS-CoV infection and transmission.",,"['Guo, Xiaojuan', 'Deng, Yao', 'Chen, Hong', 'Lan, Jiaming', 'Wang, Wen', 'Zou, Xiaohui', 'Hung, Tao', 'Lu, Zhuozhuang', 'Tan, Wenjie']",,,,
,PMC,Respiratory protease/antiprotease balance determines susceptibility to viral infection and can be modified by nutritional antioxidants,http://dx.doi.org/10.1152/ajplung.00028.2015,PMC4587599,,,"The respiratory epithelium functions as a central orchestrator to initiate and organize responses to inhaled stimuli. Proteases and antiproteases are secreted from the respiratory epithelium and are involved in respiratory homeostasis. Modifications to the protease/antiprotease balance can lead to the development of lung diseases such as emphysema or chronic obstructive pulmonary disease. Furthermore, altered protease/antiprotease balance, in favor for increased protease activity, is associated with increased susceptibility to respiratory viral infections such as influenza virus. However, nutritional antioxidants induce antiprotease expression/secretion and decrease protease expression/activity, to protect against viral infection. As such, this review will elucidate the impact of this balance in the context of respiratory viral infection and lung disease, to further highlight the role epithelial cell-derived proteases and antiproteases contribute to respiratory immune function. Furthermore, this review will offer the use of nutritional antioxidants as possible therapeutics to boost respiratory mucosal responses and/or protect against infection.",,"['Meyer, Megan', 'Jaspers, Ilona']",,,,
,PMC,Isolation and Characterization of Porcine Deltacoronavirus from Pigs with Diarrhea in the United States,http://dx.doi.org/10.1128/JCM.00031-15,PMC4400786,,,"Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes diarrhea in nursing piglets. Following its first detection in the United States in February 2014, additional PDCoV strains have been identified in the United States and Canada. Currently, no treatments or vaccines for PDCoV are available. In this study, U.S. PDCoV strain OH-FD22 from intestinal contents of a diarrheic pig from Ohio was isolated in swine testicular (ST) and LLC porcine kidney (LLC-PK) cell cultures by using various medium additives. We also isolated PDCoV [OH-FD22(DC44) strain] in LLC-PK cells from intestinal contents of PDCoV OH-FD22 strain-inoculated gnotobiotic (Gn) pigs. Cell culture isolation and propagation were optimized, and the isolates were serially propagated in cell culture for >20 passages. The full-length S and N genes were sequenced to study PDCoV genetic changes after passage in Gn pigs and cell culture (passage 11 [P11] and P20). Genetically, the S and N genes of the PDCoV isolates were relatively stable during the first 20 passages in cell culture, with only 5 nucleotide changes, each corresponding to an amino acid change. The S and N genes of our sequenced strains were genetically closely related to each other and to other U.S. PDCoV strains, with the highest sequence similarity to South Korean strain KNU14-04. This is the first report describing cell culture isolation, serial propagation, and biological and genetic characterization of cell-adapted PDCoV strains. The information presented in this study is important for the development of diagnostic reagents, assays, and potential vaccines against emergent PDCoV strains.",,"['Hu, Hui', 'Jung, Kwonil', 'Vlasova, Anastasia N.', 'Chepngeno, Juliet', 'Lu, Zhongyan', 'Wang, Qiuhong', 'Saif, Linda J.']",,,,
,PMC,Genomic and Epidemiological Characteristics Provide New Insights into the Phylogeographical and Spatiotemporal Spread of Porcine Epidemic Diarrhea Virus in Asia,http://dx.doi.org/10.1128/JCM.02898-14,PMC4400760,,,"Porcine epidemic diarrhea has become pandemic in the Asian pig-breeding industry, causing significant economic loss. In the present study, 11 complete genomes of porcine epidemic diarrhea virus (PEDV) field isolates from China were determined and analyzed. Frequently occurring mutations were observed, which suggested that full understanding of the genomic and epidemiological characteristics is critical in the fight against PEDV epidemics. Comparative analysis of 49 available genomes clustered the PEDV strains into pandemic (PX) and classical (CX) groups and identified four hypervariable regions (V1 to V4). Further study indicated key roles for the spike (S) gene and the V2 region in distinguishing between the PX and CX groups and for studying genetic evolution. Genotyping and phylogeny-based geographical dissection based on 219 S genes revealed the complexity and severity of PEDV epidemics in Asia. Many subgroups have formed, with a wide array of mutations in different countries, leading to the outbreak of PEDV in Asia. Spatiotemporal reconstruction based on the analysis suggested that the pandemic group strains originated from South Korea and then extended into Japan, Thailand, and China. However, the novel pandemic strains in South Korea that appeared after 2013 may have originated from a Chinese variant. Thus, the serious PED epidemics in China and South Korea in recent years were caused by the complex subgroups of PEDV. The data in this study have important implications for understanding the ongoing PEDV outbreaks in Asia and will guide future efforts to effectively prevent and control PEDV.",,"['Sun, Min', 'Ma, Jiale', 'Wang, Yanan', 'Wang, Ming', 'Song, Wenchao', 'Zhang, Wei', 'Lu, Chengping', 'Yao, Huochun']",,,,
,PMC,Disseminated Rhinovirus C8 Infection with Infectious Virus in Blood and Fatal Outcome in a Child with Repeated Episodes of Bronchiolitis,http://dx.doi.org/10.1128/JCM.03484-14,PMC4400751,,,"We report a fatal case of acute lower respiratory tract disease with human rhinovirus C (HRV-C) as the unique cause in a 19-month-old girl with a history of repeated episodes of bronchiolitis. HRV-C type 8 nucleic acids were observed in respiratory, stool, and cerebrospinal fluid samples, and infectious virions were isolated from patient serum after inoculation onto reconstituted airway epithelia.",,"['Lupo, Julien', 'Schuffenecker, Isabelle', 'Morel-Baccard, Christine', 'Bardet, Julie', 'Payen, Valérie', 'Kaiser, Laurent', 'Constant, Samuel', 'Lobrinus, Johannes Alexander', 'Lin-Marq, Nathalie', 'Lina, Bruno', 'Morand, Patrice', 'Tapparel, Caroline']",,,,
,PMC,Combating emerging viral threats,http://dx.doi.org/10.1126/science.aaa3778,PMC4419706,,,"Most approved antiviral therapeutics selectively inhibit proteins encoded by a single virus, thereby providing a “one drug-one bug” solution. As a result of this narrow spectrum of coverage and the high cost of drug development, therapies are currently approved for fewer than ten viruses out of the hundreds known to cause human disease. This perspective summarizes progress and challenges in the development of broad-spectrum antiviral therapies. These strategies include targeting enzymatic functions shared by multiple viruses and host cell machinery by newly discovered compounds or by repurposing approved drugs. These approaches offer new practical means for developing therapeutics against existing and emerging viral threats.",,"['Bekerman, Elena', 'Einav, Shirit']",,,,
,PMC,Whole-Genome Sequencing in Outbreak Analysis,http://dx.doi.org/10.1128/CMR.00075-13,PMC4399107,,,"In addition to the ever-present concern of medical professionals about epidemics of infectious diseases, the relative ease of access and low cost of obtaining, producing, and disseminating pathogenic organisms or biological toxins mean that bioterrorism activity should also be considered when facing a disease outbreak. Utilization of whole-genome sequencing (WGS) in outbreak analysis facilitates the rapid and accurate identification of virulence factors of the pathogen and can be used to identify the path of disease transmission within a population and provide information on the probable source. Molecular tools such as WGS are being refined and advanced at a rapid pace to provide robust and higher-resolution methods for identifying, comparing, and classifying pathogenic organisms. If these methods of pathogen characterization are properly applied, they will enable an improved public health response whether a disease outbreak was initiated by natural events or by accidental or deliberate human activity. The current application of next-generation sequencing (NGS) technology to microbial WGS and microbial forensics is reviewed.",,"['Gilchrist, Carol A.', 'Turner, Stephen D.', 'Riley, Margaret F.', 'Petri, William A.', 'Hewlett, Erik L.']",,,,
,PMC,Optimization of antigen dose for a receptor-binding domain-based subunit vaccine against MERS coronavirus,http://dx.doi.org/10.1080/21645515.2015.1021527,PMC4514392,,,"Middle East respiratory syndrome (MERS) is an emerging infectious disease caused by MERS coronavirus (MERS-CoV). The continuous increase of MERS cases has posed a serious threat to public health worldwide, calling for development of safe and effective MERS vaccines. We have previously shown that a recombinant protein containing residues 377–588 of MERS-CoV receptor-binding domain (RBD) fused with human Fc (S377-588-Fc) induced highly potent anti-MERS-CoV neutralizing antibodies in the presence of MF59 adjuvant. Here we optimized the doses of S377-588-Fc using MF59 as an adjuvant in order to elicit strong immune responses with minimal amount of antigen. Our results showed that S377-588-Fc at 1 μg was able to induce in the immunized mice potent humoral and cellular immune responses. Particularly, S377-588-Fc at 1 μg elicited strong neutralizing antibody responses against both pseudotyped and live MERS-CoV similar to those induced at 5 and 20 μg, respectively. These results suggest that this RBD-based subunit MERS vaccine candidate at the dose as low as one μg is sufficiently potent to induce strong humoral and cellular immune responses, including neutralizing antibodies, against MERS-CoV infection, thus providing guidance for determining the optimal dosage of RBD-based MERS vaccines in the future clinical trials and for applying the dose-sparing strategy in other subunit vaccine trials.",,"['Tang, Jian', 'Zhang, Naru', 'Tao, Xinrong', 'Zhao, Guangyu', 'Guo, Yan', 'Tseng, Chien-Te K', 'Jiang, Shibo', 'Du, Lanying', 'Zhou, Yusen']",,,,
,PMC,H1N1 viral proteome peptide microarray predicts individuals at risk for H1N1 infection and segregates infection versus Pandemrix® vaccination,http://dx.doi.org/10.1111/imm.12448,PMC4479535,,,"A high content peptide microarray containing the entire influenza A virus [A/California/08/2009(H1N1)] proteome and haemagglutinin proteins from 12 other influenza A subtypes, including the haemagglutinin from the [A/South Carolina/1/1918(H1N1)] strain, was used to gauge serum IgG epitope signatures before and after Pandemrix® vaccination or H1N1 infection in a Swedish cohort during the pandemic influenza season 2009. A very narrow pattern of pandemic flu-specific IgG epitope recognition was observed in the serum from individuals who later contracted H1N1 infection. Moreover, the pandemic influenza infection generated IgG reactivity to two adjacent epitopes of the neuraminidase protein. The differential serum IgG recognition was focused on haemagglutinin 1 (H1) and restricted to classical antigenic sites (Cb) in both the vaccinated controls and individuals with flu infections. We further identified a novel epitope VEPGDKITFEATGNL on the Ca antigenic site (251–265) of the pandemic flu haemagglutinin, which was exclusively recognized in serum from individuals with previous vaccinations and never in serum from individuals with H1N1 infection (confirmed by RNA PCR analysis from nasal swabs). This epitope was mapped to the receptor-binding domain of the influenza haemagglutinin and could serve as a correlate of immune protection in the context of pandemic flu. The study shows that unbiased epitope mapping using peptide microarray technology leads to the identification of biologically and clinically relevant target structures. Most significantly an H1N1 infection induced a different footprint of IgG epitope recognition patterns compared with the pandemic H1N1 vaccine.",,"['Ambati, Aditya', 'Valentini, Davide', 'Montomoli, Emanuele', 'Lapini, Guilia', 'Biuso, Fabrizio', 'Wenschuh, Holger', 'Magalhaes, Isabelle', 'Maeurer, Markus']",,,,
,PMC,Comparison of peripheral blood T lymphocyte immune function among venous thromboembolism patients with and without infection and patients with simple infection,,PMC4483919,,,"Objective: To investigate the differences of T lymphocyte subgroups and high-sensitivity C reactive protein (HsCRP) levels among patients with venous thromboembolism (VTE), VTE patients with infection, simple infection patients and the normal controls. Method: 289 patients were enrolled in this study and divided into control group, VTE group, VTE with infection group and simple infection group. Result: Compared with the control group, the serum levels of CD3(+), CD4(+), CD8(+) T lymphocytes significantly decreased and CD4(+)/CD8(+) ratio significantly increased in simple infection group (P < 0.05); CD3(+) and CD8(+) T lymphocytes significantly decreased and CD4(+)/CD8(+) ratio significantly increased in VTE and VTE with infection group (P < 0.05); the proportion of declined CD3(+) and CD8(+) T lymphocytes increased, and the proportion of increased CD4(+)/CD8(+) ratio statistically elevated in three disease groups. As an important inflammatory factor, all HsCRP levels in three disease groups significantly increased when compared with the control group. Conclusion: Immune dysfunction exists in both of VTE and infection patients, while VTE patients tend to be accompanied with infections. The changes of T lymphocyte subgroups in VTE patients, who were independent from infection, could cause T lymphocyte immune dysfunction, suggesting that there were abnormalities of T lymphocyte immune function in VTE itself. The overall T lymphocyte functions of recognizing antigens and transducing activation signals decline in VTE patients. Besides, the function of T lymphocyte of directly killing virus microbes declines significantly and the inflammatory mechanisms are involved in the occurrence and development of venous thrombosis.",,"['Zhou, Lin', 'Mao, Yu', 'Wang, Lemin', 'Jiang, Jinfa', 'Xu, Wenjun', 'Xu, Jiahong', 'Song, Haoming']",,,,
,PMC,Immunogenic Display of Purified Chemically Cross-Linked HIV-1 Spikes,http://dx.doi.org/10.1128/JVI.03738-14,PMC4468504,,,"HIV-1 envelope glycoprotein (Env) spikes are prime vaccine candidates, at least in principle, but suffer from instability, molecular heterogeneity and a low copy number on virions. We anticipated that chemical cross-linking of HIV-1 would allow purification and molecular characterization of trimeric Env spikes, as well as high copy number immunization. Broadly neutralizing antibodies bound tightly to all major quaternary epitopes on cross-linked spikes. Covalent cross-linking of the trimer also stabilized broadly neutralizing epitopes, although surprisingly some individual epitopes were still somewhat sensitive to heat or reducing agent. Immunodepletion using non-neutralizing antibodies to gp120 and gp41 was an effective method for removing non-native-like Env. Cross-linked spikes, purified via an engineered C-terminal tag, were shown by negative stain EM to have well-ordered, trilobed structure. An immunization was performed comparing a boost with Env spikes on virions to spikes cross-linked and captured onto nanoparticles, each following a gp160 DNA prime. Although differences in neutralization did not reach statistical significance, cross-linked Env spikes elicited a more diverse and sporadically neutralizing antibody response against Tier 1b and 2 isolates when displayed on nanoparticles, despite attenuated binding titers to gp120 and V3 crown peptides. Our study demonstrates display of cross-linked trimeric Env spikes on nanoparticles, while showing a level of control over antigenicity, purity and density of virion-associated Env, which may have relevance for Env based vaccine strategies for HIV-1. IMPORTANCE The envelope spike (Env) is the target of HIV-1 neutralizing antibodies, which a successful vaccine will need to elicit. However, native Env on virions is innately labile, as well as heterogeneously and sparsely displayed. We therefore stabilized Env spikes using a chemical cross-linker and removed non-native Env by immunodepletion with non-neutralizing antibodies. Fixed native spikes were recognized by all classes of known broadly neutralizing antibodies but not by non-neutralizing antibodies and displayed on nanoparticles in high copy number. An immunization experiment in rabbits revealed that cross-linking Env reduced its overall immunogenicity; however, high-copy display on nanoparticles enabled boosting of antibodies that sporadically neutralized some relatively resistant HIV-1 isolates, albeit at a low titer. This study describes the purification of stable and antigenically correct Env spikes from virions that can be used as immunogens.",,"['Leaman, Daniel P.', 'Lee, Jeong Hyun', 'Ward, Andrew B.', 'Zwick, Michael B.']",,,,
,PMC,The Vesicle-Forming 6K(2) Protein of Turnip Mosaic Virus Interacts with the COPII Coatomer Sec24a for Viral Systemic Infection,http://dx.doi.org/10.1128/JVI.00503-15,PMC4468490,,,"Positive-sense RNA viruses remodel host cell endomembranes to generate quasi-organelles known as “viral factories” to coordinate diverse viral processes, such as genome translation and replication. It is also becoming clear that enclosing viral RNA (vRNA) complexes within membranous structures is important for virus cell-to-cell spread throughout the host. In plant cells infected by turnip mosaic virus (TuMV), a member of the family Potyviridae, peripheral motile endoplasmic reticulum (ER)-derived viral vesicles are produced that carry the vRNA to plasmodesmata for delivery into adjacent noninfected cells. The viral protein 6K(2) is responsible for the formation of these vesicles, but how 6K(2) is involved in their biogenesis is unknown. We show here that 6K(2) is associated with cellular membranes. Deletion mapping and site-directed mutagenesis experiments defined a soluble N-terminal 12-amino-acid stretch, in particular a potyviral highly conserved tryptophan residue and two lysine residues that were important for vesicle formation. When the tryptophan residue was changed into an alanine in the viral polyprotein, virus replication still took place, albeit at a reduced level, but cell-to-cell movement of the virus was abolished. Yeast (Saccharomyces cerevisiae) two-hybrid and coimmunoprecipitation experiments showed that 6K(2) interacted with Sec24a, a COPII coatomer component. Appropriately, TuMV systemic movement was delayed in an Arabidopsis thaliana mutant line defective in Sec24a. Intercellular movement of TuMV replication vesicles thus requires ER export of 6K(2), which is mediated by the interaction of the N-terminal domain of the viral protein with Sec24a. IMPORTANCE Many plant viruses remodel the endoplasmic reticulum (ER) to generate vesicles that are associated with the virus replication complex. The viral protein 6K(2) of turnip mosaic virus (TuMV) is known to induce ER-derived vesicles that contain vRNA as well as viral and host proteins required for vRNA synthesis. These vesicles not only sustain vRNA synthesis, they are also involved in the intercellular trafficking of vRNA. In this investigation, we found that the N-terminal soluble domain of 6K(2) is required for ER export of the protein and for the formation of vesicles. ER export is not absolutely required for vRNA replication but is necessary for virus cell-to-cell movement. Furthermore, we found that 6K(2) physically interacts with the COPII coatomer Sec24a and that an Arabidopsis thaliana mutant line with a defective Sec24a shows a delay in the systemic infection by TuMV.",,"['Jiang, Jun', 'Patarroyo, Camilo', 'Garcia Cabanillas, Daniel', 'Zheng, Huanquan', 'Laliberté, Jean-François']",,,,
,PMC,Structural Basis for 2′-5′-Oligoadenylate Binding and Enzyme Activity of a Viral RNase L Antagonist,http://dx.doi.org/10.1128/JVI.00701-15,PMC4468480,,,"Synthesis of 2′-5′-oligoadenylates (2-5A) by oligoadenylate synthetase (OAS) is an important innate cellular response that limits viral replication by activating the latent cellular RNase, RNase L, to degrade single-stranded RNA. Some rotaviruses and coronaviruses antagonize the OAS/RNase L pathway through the activity of an encoded 2H phosphoesterase domain that cleaves 2-5A. These viral 2H phosphoesterases are phylogenetically related to the cellular A kinase anchoring protein 7 (AKAP7) and share a core structure and an active site that contains two well-defined HΦ(S/T)Φ (where Φ is a hydrophobic residue) motifs, but their mechanism of substrate binding is unknown. Here, we report the structures of a viral 2H phosphoesterase, the C-terminal domain (CTD) of the group A rotavirus (RVA) VP3 protein, both alone and in complex with 2-5A. The domain forms a compact fold, with a concave β-sheet that contains the catalytic cleft, but it lacks two α-helical regions and two β-strands observed in AKAP7 and other 2H phosphoesterases. The cocrystal structure shows significant conformational changes in the R loop upon ligand binding. Bioinformatics and biochemical analyses reveal that conserved residues and residues required for catalytic activity and substrate binding comprise the catalytic motifs and a region on one side of the binding cleft. We demonstrate that the VP3 CTD of group B rotavirus, but not that of group G, cleaves 2-5A. These findings suggest that the VP3 CTD is a streamlined version of a 2H phosphoesterase with a ligand-binding mechanism that is shared among 2H phosphodiesterases that cleave 2-5A. IMPORTANCE The C-terminal domain (CTD) of rotavirus VP3 is a 2H phosphoesterase that cleaves 2′-5′-oligoadenylates (2-5A), potent activators of an important innate cellular antiviral pathway. 2H phosphoesterase superfamily proteins contain two conserved catalytic motifs and a proposed core structure. Here, we present structures of a viral 2H phosphoesterase, the rotavirus VP3 CTD, alone and in complex with its substrate, 2-5A. The domain lacks two α-helical regions and β-strands present in other 2H phosphoesterases. A loop of the protein undergoes significant structural changes upon substrate binding. Together with our bioinformatics and biochemical findings, the crystal structures suggest that the RVA VP3 CTD domain is a streamlined version of a cellular enzyme that shares a ligand-binding mechanism with other 2H phosphodiesterases that cleave 2-5A but differs from those of 2H phosphodiesterases that cleave other substrates. These findings may aid in the future design of antivirals targeting viral phosphodiesterases with cleavage specificity for 2-5A.",,"['Ogden, Kristen M.', 'Hu, Liya', 'Jha, Babal K.', 'Sankaran, Banumathi', 'Weiss, Susan R.', 'Silverman, Robert H.', 'Patton, John T.', 'Prasad, B. V. Venkataram']",,,,
,PMC,"INTEGRATION OF SYSTEMS GLYCOBIOLOGY WITH BIOINFORMATICS TOOLBOXES, GLYCOINFORMATICS RESOURCES AND GLYCOPROTEOMICS DATA",http://dx.doi.org/10.1002/wsbm.1296,PMC4457600,,,"The glycome constitutes the entire complement of free carbohydrates and glycoconjugates expressed on whole cells or tissues. ‘Systems Glycobiology’ is an emerging discipline that aims to quantitatively describe and analyse the glycome. Here, instead of developing a detailed understanding of single biochemical processes, a combination of computational and experimental tools are used to seek an integrated or ‘systems-level’ view. This can explain how multiple biochemical reactions and transport processes interact with each other to control glycome biosynthesis and function. Computational methods in this field commonly build in silico reaction network models to describe experimental data derived from structural studies that measure cell-surface glycan distribution. While considerable progress has been made, several challenges remain due to the complex and heterogeneous nature of this post-translational modification. First, for the in silico models to be standardized and shared among laboratories, it is necessary to integrate glycan structure information and glycosylation-related enzyme definitions into the mathematical models. Second, as glycoinformatics resources grow, it would be attractive to utilize ‘Big Data’ stored in these repositories for model construction and validation. Third, while the technology for profiling the glycome at the whole-cell level has been standardized, there is a need to integrate mass spectrometry derived site-specific glycosylation data into the models. The current review discusses progress that is being made to resolve the above bottlenecks. The focus is on how computational models can bridge the gap between ‘data’ generated in wet-laboratory studies with ‘knowledge’ that can enhance our understanding of the glycome.",,"['Liu, Gang', 'Neelamegham, Sriram']",,,,
,PMC,Middle East respiratory syndrome: obstacles and prospects for vaccine development,http://dx.doi.org/10.1586/14760584.2015.1036033,PMC4832601,,,"The recent emergence of Middle East respiratory syndrome (MERS) highlights the need to engineer new methods for expediting vaccine development against emerging diseases. However, several obstacles prevent pursuit of a licensable MERS vaccine. First, the lack of a suitable animal model for MERS complicates in vivo testing of candidate vaccines. Second, due to the low number of MERS cases, pharmaceutical companies have little incentive to pursue MERS vaccine production as the costs of clinical trials are high. In addition, the timeline from bench research to approved vaccine use is 10 years or longer. Using novel methods and cost-saving strategies, genetically engineered vaccines can be produced quickly and cost-effectively. Along with progress in MERS animal model development, these obstacles can be circumvented or at least mitigated.",,"['Papaneri, Amy B.', 'Johnson, Reed F.', 'Wada, Jiro', 'Bollinger, Laura', 'Jahrling, Peter B.', 'Kuhn, Jens H.']",,,,
,PMC,Influenza induces IL-8 and GM-CSF secretion by human alveolar epithelial cells through HGF/c-Met and TGF-α/EGFR signaling,http://dx.doi.org/10.1152/ajplung.00290.2014,PMC4451400,26033355,CC BY,"The most severe complication of influenza is viral pneumonia, which can lead to the acute respiratory distress syndrome. Alveolar epithelial cells (AECs) are the first cells that influenza virus encounters upon entering the alveolus. Infected epithelial cells produce cytokines that attract and activate neutrophils and macrophages, which in turn induce damage to the epithelial-endothelial barrier. Hepatocyte growth factor (HGF)/c-Met and transforming growth factor-α (TGF-α)/epidermal growth factor receptor (EGFR) are well known to regulate repair of damaged alveolar epithelium by stimulating cell migration and proliferation. Recently, TGF-α/EGFR signaling has also been shown to regulate innate immune responses in bronchial epithelial cells. However, little is known about whether HGF/c-Met signaling alters the innate immune responses and whether the innate immune responses in AECs are regulated by HGF/c-Met and TGF-α/EGFR. We hypothesized that HGF/c-Met and TGF-α/EGFR would regulate innate immune responses to influenza A virus infection in human AECs. We found that recombinant human HGF (rhHGF) and rhTGF-α stimulated primary human AECs to secrete IL-8 and granulocyte macrophage colony-stimulating factor (GM-CSF) strongly and IL-6 and monocyte chemotactic protein 1 moderately. Influenza infection stimulated the secretion of IL-8 and GM-CSF by AECs plated on rat-tail collagen through EGFR activation likely by TGF-α released from AECs and through c-Met activated by HGF secreted from lung fibroblasts. HGF secretion by fibroblasts was stimulated by AEC production of prostaglandin E(2) during influenza infection. We conclude that HGF/c-Met and TGF-α/EGFR signaling enhances the innate immune responses by human AECs during influenza infections.",2015 Jun 1,"['Ito, Yoko', 'Correll, Kelly', 'Zemans, Rachel L.', 'Leslie, Christina C.', 'Murphy, Robert C.', 'Mason, Robert J.']",Am J Physiol Lung Cell Mol Physiol,,,
,PMC,DPP4 IN CARDIOMETABOLIC DISEASE: RECENT INSIGHTS FROM THE LABORATORY AND CLINICAL TRIALS OF DPP4 INHIBITION,http://dx.doi.org/10.1161/CIRCRESAHA.116.305665,PMC4394189,,,"The discovery of incretin-based medications represents a major therapeutic advance in the pharmacologic management of Type 2 diabetes (T2DM), as these agents avoid hypoglycemia, weight gain and simplify the management of T2DM. Dipeptidyl peptidase-4 (CD26, DPP4) inhibitors (DPP4i) are the most widely used incretin-based therapy for the treatment of T2DM globally. DPP4i are modestly effective in reducing HbA1c (≈0.5%) and while these agents were synthesized with the understanding of the role that DPP4 plays in prolonging the half-life of incretins such as glucagon like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), it is now recognized that incretins are only one of many targets of DPP4. The widespread expression of DPP4 on blood vessels, myocardium and myeloid cells and the non-enzymatic function of CD26 as a signaling and binding protein, across a wide range of species, suggest a teleological role in cardiovascular regulation and inflammation. Indeed, DPP4 is up regulated in pro-inflammatory states including obesity, T2DM and atherosclerosis. Consistent with this maladaptive role, the effects of DPP4 inhibition appear to exert a protective role in cardiovascular disease at least in pre-clinical animal models. Although 2 large clinical trials suggest a neutral effect on cardiovascular end-points, current limitations of performing trials in T2DM over a limited time horizon on top of maximal medical therapy, must be acknowledged before rendering judgment on the cardiovascular efficacy of these agents. This review will critically review the science of DPP4 and the effects of DPP4i on the cardiovascular system.",,"['Zhong, Jixin', 'Maiseyeu, Andrei', 'Davis, Stephen N.', 'Rajagopalan, Sanjay']",,,,
,PMC,Infectious Disease Modeling Methods as Tools for Informing Response to Novel Influenza Viruses of Unknown Pandemic Potential,http://dx.doi.org/10.1093/cid/civ083,PMC4481577,,,"The rising importance of infectious disease modeling makes this an appropriate time for a guide for public health practitioners tasked with preparing for, and responding to, an influenza pandemic. We list several questions that public health practitioners commonly ask about pandemic influenza and match these with analytical methods, giving details on when during a pandemic the methods can be used, how long it might take to implement them, and what data are required. Although software to perform these tasks is available, care needs to be taken to understand: (1) the type of data needed, (2) the implementation of the methods, and (3) the interpretation of results in terms of model uncertainty and sensitivity. Public health leaders can use this article to evaluate the modeling literature, determine which methods can provide appropriate evidence for decision-making, and to help them request modeling work from in-house teams or academic groups.",,"['Gambhir, Manoj', 'Bozio, Catherine', ""O'Hagan, Justin J."", 'Uzicanin, Amra', 'Johnson, Lucinda E.', 'Biggerstaff, Matthew', 'Swerdlow, David L.']",,,,
,PMC,The infant airway microbiome in health and disease impacts later asthma development,http://dx.doi.org/10.1016/j.chom.2015.03.008,PMC4433433,,,"The nasopharynx (NP) is a reservoir for microbes associated with acute respiratory illnesses (ARI). The development of asthma is initiated during infancy, driven by airway inflammation associated with infections. Here, we report viral and bacterial community profiling of NP aspirates across a birth cohort, capturing all lower respiratory illnesses during their first year. Most infants were initially colonized with Staphylococcus or Corynebacterium before stable colonization with Alloiococcus or Moraxella, with transient incursions of Streptococcus, Moraxella or Haemophilus marking virus-associated ARIs. Our data identify the NP microbiome as a determinant for infection spread to the lower airways, severity of accompanying inflammatory symptoms, and risk for future asthma development. Early asymptomatic colonization with Streptococcus was a strong asthma predictor, and antibiotic usage disrupted asymptomatic colonization patterns.",,"['Teo, Shu Mei', 'Mok, Danny', 'Pham, Kym', 'Kusel, Merci', 'Serralha, Michael', 'Troy, Niamh', 'Holt, Barbara J.', 'Hales, Belinda J.', 'Walker, Michael L.', 'Hollams, Elysia', 'Bochkov, Yury A.', 'Grindle, Kristine', 'Johnston, Sebastian L.', 'Gern, James E.', 'Sly, Peter D.', 'Holt, Patrick G.', 'Holt, Kathryn E.', 'Inouye, Michael']",,,,
,PMC,Mutations in Coronavirus Nonstructural Protein 10 Decrease Virus Replication Fidelity,http://dx.doi.org/10.1128/JVI.00110-15,PMC4474304,,,"Coronaviruses (CoVs) are unique in encoding a 3′→5′ exoribonuclease within nonstructural protein 14 (nsp14-ExoN) that is required for high-fidelity replication, likely via proofreading. nsp14 associates with the CoV RNA-dependent RNA polymerase (nsp12-RdRp), and nsp14-ExoN activity is enhanced by binding nsp10, a small nonenzymatic protein. However, it is not known whether nsp10 functions in the regulation of CoV replication fidelity. To test this, we engineered single and double alanine substitution mutations into the genome of murine hepatitis virus (MHV-A59) containing ExoN activity [ExoN(+)] at positions within nsp10 known to disrupt the nsp10-nsp14 interaction in vitro. We show that an nsp10 mutant, R80A/E82A-ExoN(+), was five to ten times more sensitive to treatment with the RNA mutagen 5-fluorouracil (5-FU) than wild-type (WT)-ExoN(+), suggestive of decreased replication fidelity. This decreased-fidelity phenotype was confirmed using two additional nucleoside analogs, 5-azacytidine and ribavirin. R80A/E82A-ExoN(+) reached a peak titer similar to and demonstrated RNA synthesis kinetics comparable to those seen with WT-ExoN(+). No change in 5-FU sensitivity was observed for R80A/E82A-ExoN(−) relative to MHV-ExoN(−), indicating that the decreased-fidelity phenotype of R80A/E82A-ExoN(−) is linked to the presence of ExoN activity. Our results demonstrate that nsp10 is important for CoV replication fidelity and support the hypothesis that nsp10 functions to regulate nsp14-ExoN activity during virus replication. IMPORTANCE The adaptive capacity of CoVs, as well as all other RNA viruses, is partially attributed to the presence of extensive population genetic diversity. However, decreased fidelity is detrimental to CoV replication and virulence; mutant CoVs with decreased replication fidelity are attenuated and more sensitive to inhibition by RNA mutagens. Thus, identifying the viral protein determinants of CoV fidelity is important for understanding CoV replication, pathogenesis, and virulence. In this report, we show that nsp10, a small, nonenzymatic viral protein, contributes to CoV replication fidelity. Our data support the hypothesis that CoVs have evolved multiple proteins, in addition to nsp14-ExoN, that are responsible for maintaining the integrity of the largest known RNA genomes.",,"['Smith, Everett Clinton', 'Case, James Brett', 'Blanc, Hervé', 'Isakov, Ofer', 'Shomron, Noam', 'Vignuzzi, Marco', 'Denison, Mark R.']",,,,
,PMC,Influenza A Virus Protein PA-X Contributes to Viral Growth and Suppression of the Host Antiviral and Immune Responses,http://dx.doi.org/10.1128/JVI.00319-15,PMC4474289,,,"Influenza virus infection causes global inhibition of host protein synthesis in infected cells. This host shutoff is thought to allow viruses to escape from the host antiviral response, which restricts virus replication and spread. Although the mechanism of host shutoff is unclear, a novel viral protein expressed by ribosomal frameshifting, PA-X, was found to play a major role in influenza virus-induced host shutoff. However, little is known about the impact of PA-X expression on currently circulating influenza A virus pathogenicity and the host antiviral response. In this study, we rescued a recombinant influenza A virus, A/California/04/09 (H1N1, Cal), containing mutations at the frameshift motif in the polymerase PA gene (Cal PA-XFS). Cal PA-XFS expressed significantly less PA-X than Cal wild type (WT). Cal WT, but not Cal PA-XFS, induced degradation of host β-actin mRNA and suppressed host protein synthesis, supporting the idea that PA-X induces host shutoff via mRNA decay. Moreover, Cal WT inhibited beta interferon (IFN-β) expression and replicated more rapidly than Cal PA-XFS in human respiratory cells. Mice infected with Cal PA-XFS had significantly lower levels of viral growth and greater expression of IFN-β mRNA in their lungs than mice infected with Cal WT. Importantly, more antihemagglutinin and neutralizing antibodies were produced in Cal PA-XFS-infected mice than in Cal WT-infected mice, despite the lower level of virus replication in the lungs. Our data indicate that PA-X of the pandemic H1N1 virus has a strong impact on viral growth and the host innate and acquired immune responses to influenza virus. IMPORTANCE Virus-induced host protein shutoff is considered to be a major factor allowing viruses to evade innate and acquired immune recognition. We provide evidence that the 2009 H1N1 influenza A virus protein PA-X plays a role in virus replication and inhibition of host antiviral response by means of its host protein synthesis shutoff activity both in vitro and in vivo. We also demonstrated that, while the growth of Cal PA-XFS was attenuated in the lungs of infected animals, this mutant induced a stronger humoral response than Cal WT. Our findings clearly highlight the importance of PA-X in counteracting the host innate and acquired immune responses to influenza virus, an important global pathogen. This work demonstrates that inhibition of PA-X expression in influenza virus vaccine strains may provide a novel way of safely attenuating viral growth while inducing a more robust immune response.",,"['Hayashi, Tsuyoshi', 'MacDonald, Leslie A.', 'Takimoto, Toru']",,,,
,PMC,Interaction between TIM-1 and NPC1 Is Important for Cellular Entry of Ebola Virus,http://dx.doi.org/10.1128/JVI.03156-14,PMC4474285,,,"Multiple host molecules are known to be involved in the cellular entry of filoviruses, including Ebola virus (EBOV); T-cell immunoglobulin and mucin domain 1 (TIM-1) and Niemann-Pick C1 (NPC1) have been identified as attachment and fusion receptors, respectively. However, the molecular mechanisms underlying the entry process have not been fully understood. We found that TIM-1 and NPC1 colocalized and interacted in the intracellular vesicles where EBOV glycoprotein (GP)-mediated membrane fusion occurred. Interestingly, a TIM-1-specific monoclonal antibody (MAb), M224/1, prevented GP-mediated membrane fusion and also interfered with the binding of TIM-1 to NPC1, suggesting that the interaction between TIM-1 and NPC1 is important for filovirus membrane fusion. Moreover, MAb M224/1 efficiently inhibited the cellular entry of viruses from all known filovirus species. These data suggest a novel mechanism underlying filovirus membrane fusion and provide a potential cellular target for antiviral compounds that can be universally used against filovirus infections. IMPORTANCE Filoviruses, including Ebola and Marburg viruses, cause rapidly fatal diseases in humans and nonhuman primates. There are currently no approved vaccines or therapeutics for filovirus diseases. In general, the cellular entry step of viruses is one of the key mechanisms to develop antiviral strategies. However, the molecular mechanisms underlying the entry process of filoviruses have not been fully understood. In this study, we demonstrate that TIM-1 and NPC1, which serve as attachment and fusion receptors for filovirus entry, interact in the intracellular vesicles where Ebola virus GP-mediated membrane fusion occurs and that this interaction is important for filovirus infection. We found that filovirus infection and GP-mediated membrane fusion in cultured cells were remarkably suppressed by treatment with a TIM-1-specific monoclonal antibody that interfered with the interaction between TIM-1 and NPC1. Our data provide new insights for the development of antiviral compounds that can be universally used against filovirus infections.",,"['Kuroda, Makoto', 'Fujikura, Daisuke', 'Nanbo, Asuka', 'Marzi, Andrea', 'Noyori, Osamu', 'Kajihara, Masahiro', 'Maruyama, Junki', 'Matsuno, Keita', 'Miyamoto, Hiroko', 'Yoshida, Reiko', 'Feldmann, Heinz', 'Takada, Ayato']",,,,
,PMC,HIV Blocks Interferon Induction in Human Dendritic Cells and Macrophages by Dysregulation of TBK1,http://dx.doi.org/10.1128/JVI.00889-15,PMC4468486,,,"Dendritic cells (DCs) and macrophages are present in the tissues of the anogenital tract, where HIV-1 transmission occurs in almost all cases. These cells are both target cells for HIV-1 and represent the first opportunity for the virus to interfere with innate recognition. Previously we have shown that both cell types fail to produce type I interferons (IFNs) in response to HIV-1 but that, unlike T cells, the virus does not block IFN induction by targeting IFN regulatory factor 3 (IRF3) for cellular degradation. Thus, either HIV-1 inhibits IFN induction by an alternate mechanism or, less likely, these cells fail to sense HIV-1. Here we show that HIV-1 (but not herpes simplex virus 2 [HSV-2] or Sendai virus)-exposed DCs and macrophages fail to induce the expression of all known type I and III IFN genes. These cells do sense the virus, and pattern recognition receptor (PRR)-induced signaling pathways are triggered. The precise stage in the IFN-inducing signaling pathway that HIV-1 targets to block IFN induction was identified; phosphorylation but not K63 polyubiquitination of TANK-binding kinase 1 (TBK1) was completely inhibited. Two HIV-1 accessory proteins, Vpr and Vif, were shown to bind to TBK1, and their individual deletion partly restored IFN-β expression. Thus, the inhibition of TBK1 autophosphorylation by binding of these proteins appears to be the principal mechanism by which HIV-1 blocks type I and III IFN induction in myeloid cells. IMPORTANCE Dendritic cells (DCs) and macrophages are key HIV target cells. Therefore, definition of how HIV impairs innate immune responses to initially establish infection is essential to design preventative interventions, especially by restoring initial interferon production. Here we demonstrate how HIV-1 blocks interferon induction by inhibiting the function of a key kinase in the interferon signaling pathway, TBK1, via two different viral accessory proteins. Other viral proteins have been shown to target the general effects of TBK1, but this precise targeting between ubiquitination and phosphorylation of TBK1 is novel.",,"['Harman, Andrew N.', 'Nasr, Najla', 'Feetham, Alexandra', 'Galoyan, Ani', 'Alshehri, Abdullateef A.', 'Rambukwelle, Dharshini', 'Botting, Rachel A.', 'Hiener, Bonnie M.', 'Diefenbach, Eve', 'Diefenbach, Russell J.', 'Kim, Min', 'Mansell, Ashley', 'Cunningham, Anthony L.']",,,,
,PMC,Repurposing of the antihistamine chlorcyclizine and related compounds for treatment of hepatitis C virus infection,http://dx.doi.org/10.1126/scitranslmed.3010286,PMC6420960,,,"Hepatitis C virus (HCV) infection affects an estimated 185 million people worldwide, with chronic infection often leading to liver cirrhosis and hepatocellular carcinoma. Although HCV is curable, there is an unmet need for the development of effective and affordable treatment options. Through a cell-based high-throughput screen, we identified chlorcyclizine HCl (CCZ), an over-the-counter drug for allergy symptoms, as a potent inhibitor of HCV infection. CCZ inhibited HCV infection in human hepatoma cells and primary human hepatocytes. The mode of action of CCZ is mediated by inhibiting an early stage of HCV infection, probably targeting viral entry into host cells. The in vitro antiviral effect of CCZ was synergistic with other anti-HCV drugs, including ribavirin, interferon-α, telaprevir, boceprevir, sofosbuvir, daclatasvir, and cyclosporin A, without significant cytotoxicity, suggesting its potential in combination therapy of hepatitis C. In the mouse pharmaco­kinetic model, CCZ showed preferential liver distribution. In chimeric mice engrafted with primary human hepatocytes, CCZ significantly inhibited infection of HCV genotypes 1b and 2a, without evidence of emergence of drug resistance, during 4 and 6 weeks of treatment, respectively. With its established clinical safety profile as an allergy medication, affordability, and a simple chemical structure for optimization, CCZ represents a promising candidate for drug repurposing and further development as an effective and accessible agent for treatment of HCV infection.",,"['He, Shanshan', 'Lin, Billy', 'Chu, Virginia', 'Hu, Zongyi', 'Hu, Xin', 'Xiao, Jingbo', 'Wang, Amy Q.', 'Schweitzer, Cameron J.', 'Li, Qisheng', 'Imamura, Michio', 'Hiraga, Nobuhiko', 'Southall, Noel', 'Ferrer, Marc', 'Zheng, Wei', 'Chayama, Kazuaki', 'Marugan, Juan J.', 'Liang, T. Jake']",,,,
,PMC,Clinical Outcomes Associated With Respiratory Virus Detection Before Allogeneic Hematopoietic Stem Cell Transplant,http://dx.doi.org/10.1093/cid/civ272,PMC4565994,,,"Background. The management of respiratory virus infections prior to hematopoietic cell transplant (HCT) is difficult. We examined whether respiratory virus detection before HCT influenced the requirement for bronchoscopy, hospitalization, and overall survival following HCT. Methods. Pre-HCT and weekly post-HCT nasal washes were collected through day 100 from patients with and without symptoms. Samples were tested by multiplex polymerase chain reaction for respiratory syncytial virus, parainfluenza viruses 1–4, influenza A and B, human metapneumovirus, adenovirus, and human rhinoviruses, coronaviruses, and bocavirus. Results. Of 458 patients, 116 (25%) had respiratory viruses detected pre-HCT. Overall, patients with viruses detected pre-HCT had fewer days alive and out of the hospital and lower survival at day 100 (adjusted hazard ratio [aHR], 2.4; 95% confidence interval [CI], 1.3–4.5; P = .007) than patients with negative samples; this risk was also present with rhinovirus alone (aHR for mortality, 2.6; 95% CI, 1.2–5.5; P = .01). No difference in bronchoscopy incidence was seen in patients with and without respiratory viruses (aHR, 1.3; 95% CI, .8–2.0; P = .32). In symptomatic patients, those with respiratory viruses detected had increased overall mortality compared with patients without viruses detected (unadjusted HR, 3.5; 95% CI, 1.0–12.1; P = .05); among asymptomatic patients, detection of respiratory viruses was not associated with increased mortality. Conclusions. These data support routine testing for respiratory viruses among symptomatic patients before HCT, and delay of transplant with virus detection when feasible, even for detection of rhinovirus alone. Further study is needed to address whether asymptomatic patients should undergo screening for respiratory virus detection before HCT.",,"['Campbell, Angela P.', 'Guthrie, Katherine A.', 'Englund, Janet A.', 'Farney, Robert M.', 'Minerich, Elisa L.', 'Kuypers, Jane', 'Corey, Lawrence', 'Boeckh, Michael']",,,,
,PMC,Clinical associations of host genetic variations in the genes of cytokines in critically ill patients,http://dx.doi.org/10.1111/cei.12592,PMC4449781,,,"Host genetic variations may influence a changing profile of biochemical markers and outcome in patients with trauma/injury. The objective of this study was to assess clinical associations of single nucleotide polymorphisms (SNPs) in the genes of cytokines in critically ill patients. A total of 430 patients were genotyped for SNPs in the genes of pro- (IL1B, IL6, IL8) and anti-inflammatory (IL4, IL10, IL13) cytokines. The main end-points were sepsis, mortality and adult respiratory distress syndrome (ARDS). We evaluated the dynamic levels of bilirubin, blood urea nitrogen, creatine kinase, creatinine and lactate dehydrogenase in five points of measurements (between 1 and 14 days after admission) and correlated them with SNPs. High-producing alleles of proinflammatory cytokines protected patients against sepsis (IL1B −511A and IL8 —251A) and mortality (IL1B −511A). High-producing alleles of anti-inflammatory cytokines IL4 —589T and IL13 431A (144Gln) were less frequent in ARDS patients. The carriers of IL6 —174C/C genotypes were prone to the increased levels of biochemical markers and acute kidney and liver insufficiency. Genotype-dependent differences in the levels of biochemical indicators gradually increased to a maximal value on the 14th day after admission. These findings suggest that genetic variability in pro- and anti-inflammatory cytokines may contribute to different clinical phenotypes in patients at high risk of critical illness.",,"['Belopolskaya, O B', 'Smelaya, T V', 'Moroz, V V', 'Golubev, A M', 'Salnikova, L E']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00584-15,PMC4403486,,,,,,,,,
,PMC,Obtaining Efficacy Data in an Environment of Variable and Uncertain Incidence: Ebola and Beyond,http://dx.doi.org/10.1126/science.aaa3178,PMC4408019,,,,,"['Lipsitch, Marc', 'Eyal, Nir', 'Halloran, M. Elizabeth', 'Hernán, Miguel A.', 'Longini, Ira M.', 'Perencevich, Eli N.', 'Grais, Rebecca F.']",,,,
,PMC,Ebola preparedness: a rapid needs assessment of critical care in a tertiary hospital,http://dx.doi.org/10.9778/cmajo.20150025,PMC4565178,,,"BACKGROUND: The current outbreak of Ebola has been declared a public health emergency of international concern. We performed a rigorous and rapid needs assessment to identify the desired results, the gaps in current practice, and the barriers and facilitators to the development of solutions in the provision of critical care to patients with suspected or confirmed Ebola. METHODS: We conducted a qualitative study with an emergent design at a tertiary hospital in Ontario, Canada, recently designated as an Ebola centre, from Oct. 21 to Nov. 7, 2014. Participants included physicians, nurses, respiratory therapists, and staff from infection control, housekeeping, waste management, administration, facilities, and occupational health and safety. Data collection included document analysis, focus groups, interviews and walk-throughs of critical care areas with key stakeholders. RESULTS: Fifteen themes and 73 desired results were identified, of which 55 had gaps. During the study period, solutions were implemented to fully address 8 gaps and partially address 18 gaps. Themes identified included the following: screening; response team activation; personal protective equipment; postexposure to virus; patient placement, room setup, logging and signage; intrahospital patient movement; interhospital patient movement; critical care management; Ebola-specific diagnosis and treatment; critical care staffing; visitation and contacts; waste management, environmental cleaning and management of linens; postmortem; conflict resolution; and communication. INTERPRETATION: This investigation identified widespread gaps across numerous themes; as such, we have been able to develop a set of credible and measureable results. All hospitals need to be prepared for contact with a patient with Ebola, and the preparedness plan will need to vary based on local context, resources and site designation.",,"['Sarti, Aimee J.', 'Sutherland, Stephanie', 'Robillard, Nicholas', 'Kim, John', 'Dupuis, Kirsten', 'Thornton, Mary', 'Mansour, Marlene', 'Cardinal, Pierre']",,,,
,PMC,"Clinical description of human bocavirus viremia in children with LRTI, Eastern Province, Saudi Arabia",http://dx.doi.org/10.4103/1817-1737.151437,PMC4375745,25829968,CC BY-NC-SA,"Human bocavirus (HBoV) is a major etiology of lower respiratory tract infection (LRTI) in young children. We tested 149 patients admitted to King Fahd Hospital of the University with diagnosis of LRTI. Viremia caused by the different studied viruses was detected in 31.5% of the total cases by Real-time Polymerase chain reaction. We report five patients who were positive for HBoV in serum samples. Clinical presentation ranged from mild to severe disease as one of them required admission to intensive care unit. Wheezing was a striking feature in most of our patients, but fever was not a consistent finding.",2015 Apr-Jun,"['Bubshait, Dalal K.', 'Albuali, Waleed Hamad', 'Yousef, Abdullah A.', 'Obeid, Obeid Elteifi', 'Alkharsah, Khaled R.', 'Hassan, Manal Ismaeel', 'Vatte, Chittibabu', 'Alzahrani, Alhusain J.', 'Bukhari, Huda']",Ann Thorac Med,,,
,PMC,Detection of Human Bocavirus DNA by Multiplex PCR Analysis: Postmortem Case Report,http://dx.doi.org/10.5152/balkanmedj.2015.15254,PMC4432707,,,"BACKGROUND: Human bocavirus (HBoV) is a virus belonging to the Parvoviridae family, which has been newly discovered to be associated with respiratory tract infections in children. There are many reports worldwide on the endemicity of this virus. Since it is relatively new, it is not routinely detected in clinical laboratory investigations. CASE REPORT: We demonstrated that HBoV infection caused the death of a 5-month-old girl with a history of high fever and wheezing. Human bocavirus (HBoV 1/2/3/4) was found in a nasopharyngeal swab, paraffin-embedded lung tissue and stool samples by multiplex PCR methods using postmortem microbiological analysis. CONCLUSION: This case suggests that lower respiratory tract infections due to HBoV may cause severe and life-threatening diseases. Postmortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. To our knowledge, this report is the first document of a HBoV postmortem case in Turkey.",,"['Ziyade, Nihan', 'Şirin, Gözde', 'Elgörmüş, Neval', 'Daş, Taner']",,,,
,PMC,In vitro evaluation of pathogen-inactivated buffy coat-derived platelet concentrates during storage: psoralen-based photochemical treatment step-by-step,http://dx.doi.org/10.2450/2014.0082-14,PMC4385074,,,"BACKGROUND: The Intercept Blood System(TM) (Cerus) is used to inactivate pathogens in platelet concentrates (PC). The aim of this study was to elucidate the extent to which the Intercept treatment modifies the functional properties of platelets. MATERIAL AND METHODS: A two-arm study was conducted initially to compare buffy coat-derived pathogen-inactivated PC to untreated PC (n=5) throughout storage. A four-arm study was then designed to evaluate the contribution of the compound adsorbing device (CAD) and ultraviolet (UV) illumination to the changes observed upon Intercept treatment. Intercept-treated PC, CAD-incubated PC, and UV-illuminated PC were compared to untreated PC (n=5). Functional characteristics were assessed using flow cytometry, hypotonic shock response (HSR), aggregation, adhesion assays and flow cytometry for the detection of CD62P, CD42b, GPIIb-IIIa, phosphatidylserine exposure and JC-1 aggregates. RESULTS: Compared to fresh platelets, end-of-storage platelets exhibited greater passive activation, disruption of the mitochondrial transmembrane potential (Δψ(m)), and phosphatidylserine exposure accompanied by a decreased capacity to respond to agonist-induced aggregation, lower HSR, and CD42b expression. The Intercept treatment resulted in significantly lower HSR and CD42b expression compared to controls on day 7, with no significant changes in CD62P, Δψ(m), or phosphatidylserine exposure. GPIIbIIIa expression was significantly increased in Intercept-treated platelets throughout the storage period. The agonist-induced aggregation response was highly dependent on the type and concentration of agonist used, indicating a minor effect of the Intercept treatment. The CAD and UV steps alone had a negligible effect on platelet aggregation. DISCUSSION: The Intercept treatment moderately affects platelet function in vitro. CAD and UV illumination alone make negligible contributions to the changes in aggregation observed in Intercept-treated PC.",,"['Abonnenc, Mélanie', 'Sonego, Giona', 'Kaiser-Guignard, Julie', 'Crettaz, David', 'Prudent, Michel', 'Tissot, Jean-Daniel', 'Lion, Niels']",,,,
,PMC,Immunological profiling in chronic rhinosinusitis with nasal polyps reveals distinct VEGF and GMCSF signatures during symptomatic exacerbations,http://dx.doi.org/10.1111/cea.12463,PMC4459602,,,"BACKGROUND: The mechanisms and immune pathways associated with chronic rhinosinusitis (CRS) are not fully understood. Immunological changes during acute exacerbation of CRS may provide valuable clues to the pathogenesis and perpetuation of the disease. OBJECTIVE: To characterize local and systemic immune responses associated with acute worsening of sinonasal symptoms during exacerbation in CRS with nasal polyps (CRSwNP) compared to controls. METHODS: This was a noninterventional prospective study of individuals with CRSwNP and normal controls. Subjects underwent a baseline visit with collection of nasal secretions, nasal washes, and serum specimens. Within 3 days of acute worsening of sinonasal symptoms, subjects underwent a study visit, followed by a post-visit 2 weeks later. The Sinonasal Outcome Test-22 (SNOT-22) scores and immunological parameters in the specimens were analyzed using a novel, unsupervised learning method and by conventional univariate analysis. RESULTS: Both CRSwNP patients and control subjects showed a significant increase in SNOT-22 scores during acute exacerbation. Increased nasal levels of IL-6, IL-5, and eosinophil major basic protein were observed in CRSwNP patients. A network analysis of serum specimens revealed changes in a set of immunological parameters, which are distinctly associated with CRSwNP but not with controls. In particular, systemic increases in VEGF and GM-CSF levels were notable and were validated by a conventional analysis. CONCLUSIONS: CRSwNP patients demonstrate distinct immunological changes locally and systemically during acute exacerbation. Growth factors VEGF and GM-CSF may be involved in the immunopathogenesis of subjects with CRS and nasal polyps experiencing exacerbation.",,"['Divekar, Rohit D.', 'Samant, Shefali', 'Rank, Matthew A.', 'Hagan, John', 'Lal, Devyani', 'O’Brien, Erin K.', 'Kita, Hirohito']",,,,
,PMC,Hepatic Lipidosis in a Research Colony of Big Brown Bats (Eptesicus fuscus),,PMC4408899,,,"During a nearby construction project, a sudden decrease in food intake and guano production occurred in an outdoor colony of big brown bats (Eptesicus fuscus), and one animal was found dead. Investigation revealed that the project was generating a large amount of noise and vibration, which disturbed the bats’ feeding. Consequently the bats were moved into an indoor enclosure away from the construction noises, and the colony resumed eating. Over the next 3 wk, additional animals presented with clinical signs of lethargy, weight loss, ecchymoses, and icterus and were necropsied. Gross necropsy of the affected bats revealed large, pale yellow to tan, friable livers with rounded edges that floated when placed in 10% neutral-buffered formalin. Some bats had ecchymoses on the webbing and skin and gross perirenal hemorrhage. Histologic examination showed hepatic and renal tubular lipidosis. The clinical and pathologic signs of hemorrhage and icterus were suggestive of hepatic failure. Hepatic lipidosis was attributed to stress and inappetence associated with environmental perturbations. Once the environmental stressor was removed, the colony morbidity and mortality decreased. However, 2 y later, a series of new environmental stressors triggered additional deaths associated with hepatic lipidosis. Over a 9-y period, 21 cases of hepatic lipidosis were diagnosed in this bat colony.",,"['Snyder, Jessica M', 'Treuting, Piper M', 'Brabb, Thea', 'Miller, Kimberly E', 'Covey, Ellen', 'Lencioni, Karen L']",,,,
,PMC,Evaluation of cystatin C activities against HIV,http://dx.doi.org/10.4103/0971-5916.159282,PMC4510722,26112843,CC BY-NC-SA,"BACKGROUND & OBJECTIVES: Several host defense proteins known to possess antimicrobial activities are present on mucosal surfaces and are consequently found in body fluids of vertebrates. Naturally occurring protease inhibitors like cystatins, especially cystatin C (cys C), are abundantly present in human seminal plasma. Although its antiviral activity against herpes simplex virus (HSV) has been demonstrated, the role of this protein against HIV is not well studied. Therefore, the aim of the present study was to evaluate the anti-HIV activities of cys C, which is present innately in the male reproductive tract. METHODS: Protein-protein interaction of cys C with various HIV proteins was studied using a commercially available HIV blot and specific interaction with HIV protease was studied by dot-blot technique using commercially available cys C. To purify biologically active cys C from human seminal plasma to be used for subsequent experiments, gel-permeation chromatography followed by affinity chromatography was used. The HIV infectivity inhibition activity of the purified cystatin C was tested in TZM-bl cells. To study its activity on HIV protease, time-course enzyme kinetics studies were performed using spectrometric assay. RESULTS: Cystatin C reacted with some HIV proteins including HIV protease. Biologically active cys C was purified using gel permeation chromatography followed by affinity chromatography. When tested in TZM-bl cells, purified cystatin C demonstrated HIV-infectivity inhibitory activity (IC(50): 0.28 μM). Enzyme kinetic studies demonstrated that it abrogated the action of HIV protease on its substrate. INTERPRETATION & CONCLUSIONS: The present data demonstrate that cystatin C possesses anti-HIV activities. Molecular models need to be designed with this protein which would assist towards prevention/therapeutics against HIV.",2015 Apr,"['Vernekar, Vandana', 'Velhal, Shilpa', 'Bandivdekar, Atmaram']",Indian J Med Res,,,
,PMC,New potential role of serum apolipoprotein E mediated by its binding to clumping factor A during Staphylococcus aureus invasive infections to humans,http://dx.doi.org/10.1099/jmm.0.000010,PMC4857444,,,"Staphylococcus aureus is a crucial human pathogen expressing various immune-evasion proteins that interact with the host-cell molecules. Clumping factor A (ClfA) is a microbial surface protein that promotes S. aureus binding to fibrinogen, and is associated with septic arthritis and infective endocarditis. In order to identify the major human serum proteins that bind the ClfA, we utilized recombinant ClfA region A in a plate-based assay. SDS-PAGE analysis of the bound proteins yielded five prominent bands, which were analysed by MS yielding apolipoprotein E (ApoE) as the predominant protein. ClfA-sufficient S. aureus bound purified ApoE by more than one log greater than an isogenic ClfA-deficient mutant. An immunodot-blot assay yielded a linearity model for ClfA binding to human ApoE with a stoichiometric-binding ratio of 1.702 at maximal Pearson's correlation coefficient (0.927). These data suggest that ApoE could be a major and novel binding target for the S. aureus virulence factor ClfA. Thus, ClfA recruitment of serum ApoE to the S. aureus surface may sequester ApoE and blunt its host defence function against S. aureus-invasive infections to humans. In this context, compounds that can block or suppress ClfA binding to ApoE might be utilized as prophylactic or therapeutic agents.",,"['Elkhatib, Walid F.', 'Hair, Pamela S.', 'Nyalwidhe, Julius O.', 'Cunnion, Kenji M.']",,,,
,PMC,Harnessing fetal and adult genetic reprograming for therapy of heart disease,,PMC4394627,,,"Heart is the first organ formed during organogenesis. The fetal heart undergoes several structural and functional modifications to form the four-chambered mammalian heart. The adult heart shows different adaptations during compensatory and decompensatory heart failure. However, one common adaptation in the pathological heart is fetal reprogramming, where the adult heart expresses several genes and miRNAs which are active in the fetal stage. The fetal reprogramming in the failing heart raises several questions, such as whether the switch of adult to fetal genetic programming is an adaptive response to cope with adverse remodeling of the heart, does the expression of fetal genes protect the heart during compensatory and/or decompensatory heart failure, does repressing the fetal gene in the failing heart is protective to the heart? To answer these questions, we need to understand the expression of genes and miRNAs that are reprogrammed in the failing heart. In view of this, we provided an overview of differentially expressed genes and miRNAs, and their regulation in this review. Further, we elaborated novel strategies for a plausible future therapy of cardiovascular diseases.",,"['Nandi, Shyam Sundar', 'Mishra, Paras Kumar']",,,,
,PMC,Morphogenesis of Endoplasmic Reticulum Membrane-Invaginated Vesicles during Beet Black Scorch Virus Infection: Role of Auxiliary Replication Protein and New Implications of Three-Dimensional Architecture,http://dx.doi.org/10.1128/JVI.00401-15,PMC4474299,,,"All well-characterized positive-strand RNA viruses[(+)RNA viruses] induce the formation of host membrane-bound viral replication complexes (VRCs), yet the underlying mechanism and machinery for VRC formation remain elusive. We report here the biogenesis and topology of the Beet black scorch virus (BBSV) replication complex. Distinct cytopathological changes typical of endoplasmic reticulum (ER) aggregation and vesiculation were observed in BBSV-infected Nicotiana benthamiana cells. Immunogold labeling of the auxiliary replication protein p23 and double-stranded RNA (dsRNA) revealed that the ER-derived membranous spherules provide the site for BBSV replication. Further studies indicated that p23 plays a crucial role in mediating the ER rearrangement. Three-dimensional electron tomographic analysis revealed the formation of multiple ER-originated vesicle packets. Each vesicle packet enclosed a few to hundreds of independent spherules that were invaginations of the ER membranes into the lumen. Strikingly, these vesicle packets were connected to each other via tubules, a rearrangement event that is rare among other virus-induced membrane reorganizations. Fibrillar contents within the spherules were also reconstructed by electron tomography, which showed diverse structures. Our results provide the first, to our knowledge, three-dimensional ultrastructural analysis of membrane-bound VRCs of a plant (+)RNA virus and should help to achieve a better mechanistic understanding of the organization and microenvironment of plant (+)RNA virus replication complexes. IMPORTANCE Assembly of virus replication complexes for all known positive-strand RNA viruses depends on the extensive remodeling of host intracellular membranes. Beet black scorch virus, a necrovirus in the family Tombusviridae, invaginates the endoplasmic reticulum (ER) membranes to form spherules in infected cells. Double-stranded RNAs, the viral replication intermediate, and the viral auxiliary replication protein p23 are all localized within such viral spherules, indicating that these are the sites for generating progeny viral RNAs. Furthermore, the BBSV p23 protein could to some extent reorganize the ER when transiently expressed in N. benthamiana. Electron tomographic analysis resolves the three-dimensional (3D) architecture of such spherules, which are connected to the cytoplasm via a neck-like structure. Strikingly, different numbers of spherules are enclosed in ER-originated vesicle packets that are connected to each other via tubule-like structures. Our results have significant implications for further understanding the mechanisms underlying the replication of positive-strand RNA viruses.",,"['Cao, Xiuling', 'Jin, Xuejiao', 'Zhang, Xiaofeng', 'Li, Ying', 'Wang, Chunyan', 'Wang, Xianbing', 'Hong, Jian', 'Wang, Xiaofeng', 'Li, Dawei', 'Zhang, Yongliang']",,,,
,PMC,Coronavirus and Influenza Virus Proteolytic Priming Takes Place in Tetraspanin-Enriched Membrane Microdomains,http://dx.doi.org/10.1128/JVI.00543-15,PMC4442435,,,"Coronaviruses (CoVs) and low-pathogenicity influenza A viruses (LP IAVs) depend on target cell proteases to cleave their viral glycoproteins and prime them for virus-cell membrane fusion. Several proteases cluster into tetraspanin-enriched microdomains (TEMs), suggesting that TEMs are preferred virus entry portals. Here we found that several CoV receptors and virus-priming proteases were indeed present in TEMs. Isolated TEMs, when mixed with CoV and LP IAV pseudoparticles, cleaved viral fusion proteins to fusion-primed fragments and potentiated viral transductions. That entering viruses utilize TEMs as a protease source was further confirmed using tetraspanin antibodies and tetraspanin short hairpin RNAs (shRNAs). Tetraspanin antibodies inhibited CoV and LP IAV infections, but their virus-blocking activities were overcome by expressing excess TEM-associated proteases. Similarly, cells with reduced levels of the tetraspanin CD9 resisted CoV pseudoparticle transductions but were made susceptible by overproducing TEM-associated proteases. These findings indicated that antibodies and CD9 depletions interfere with viral proteolytic priming in ways that are overcome by surplus proteases. TEMs appear to be exploited by some CoVs and LP IAVs for appropriate coengagement with cell receptors and proteases. IMPORTANCE Enveloped viruses use their surface glycoproteins to catalyze membrane fusion, an essential cell entry step. Host cell components prime these viral surface glycoproteins to catalyze membrane fusion at specific times and places during virus cell entry. Among these priming components are proteases, which cleave viral surface glycoproteins, unleashing them to refold in ways that catalyze virus-cell membrane fusions. For some enveloped viruses, these proteases are known to reside on target cell surfaces. This research focuses on coronavirus and influenza A virus cell entry and identifies TEMs as sites of viral proteolysis, thereby defining subcellular locations of virus priming with greater precision. Implications of these findings extend to the use of virus entry antagonists, such as protease inhibitors, which might be most effective when localized to these microdomains.",,"['Earnest, James T.', 'Hantak, Michael P.', 'Park, Jung-Eun', 'Gallagher, Tom']",,,,
,PMC,The Physiology of Protein S-acylation,http://dx.doi.org/10.1152/physrev.00032.2014,PMC4551212,,,"Protein S-acylation, the only fully reversible posttranslational lipid modification of proteins, is emerging as a ubiquitous mechanism to control the properties and function of a diverse array of proteins and consequently physiological processes. S-acylation results from the enzymatic addition of long-chain lipids, most typically palmitate, onto intracellular cysteine residues of soluble and transmembrane proteins via a labile thioester linkage. Addition of lipid results in increases in protein hydrophobicity that can impact on protein structure, assembly, maturation, trafficking, and function. The recent explosion in global S-acylation (palmitoyl) proteomic profiling as a result of improved biochemical tools to assay S-acylation, in conjunction with the recent identification of enzymes that control protein S-acylation and de-acylation, has opened a new vista into the physiological function of S-acylation. This review introduces key features of S-acylation and tools to interrogate this process, and highlights the eclectic array of proteins regulated including membrane receptors, ion channels and transporters, enzymes and kinases, signaling adapters and chaperones, cell adhesion, and structural proteins. We highlight recent findings correlating disruption of S-acylation to pathophysiology and disease and discuss some of the major challenges and opportunities in this rapidly expanding field.",,"['Chamberlain, Luke H.', 'Shipston, Michael J.']",,,,
,PMC,Development of an Antigen Capture Enzyme-Linked Immunosorbent Assay for Virus Detection Based on Porcine Epidemic Diarrhea Virus Monoclonal Antibodies,http://dx.doi.org/10.1089/vim.2014.0065,PMC4390212,,,"Porcine epidemic diarrhea virus (PEDV), a coronavirus, can cause acute diarrhea and dehydration in pigs. In the current study, two positive monoclonal cell lines (5D7 and 3H4) specific for PEDV were established, and the immunoreactivity of the monoclonal antibodies was confirmed by immunofluorescence and dot-immunobinding assays. A method, termed antigen capture enzyme-linked immunosorbent assay (AC-ELISA), which used the monoclonal antibody 5D7 as the detecting antibody and rabbit antiserum of PEDV protein S as the capture antibody, was developed. Compared with the reverse transcription polymerase chain reaction method of detecting PEDV in fecal samples, AC-ELISA showed similar sensitivity and specificity. These results suggested that AC-ELISA would be useful for the diagnosis and epidemiological studies of PEDV.",,"['Wang, Zanyu', 'Jiyuan, Yin', 'Su, Chen', 'Xinyuan, Qiao', 'Lijie, Tang', 'Yijing, Li']",,,,
,PMC,Antiviral Activity of Chloroquine Against Dengue Virus Type 2 Replication in Aotus Monkeys,http://dx.doi.org/10.1089/vim.2014.0090,PMC4390208,,,"Dengue virus (DENV) of the Flaviviridae family is a single positive-stranded RNA virus that is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. The objective of this study was to investigate the use of chloroquine (CLQ) as an antiviral drug against dengue virus in monkeys. To analyze the action of the drug in vivo, nonhuman primates groups (Aotus azarai infulatus) were inoculated with a subcutaneous injection of a virulent strain of DENV-2, treated and untreated CLQ. Blood hematological, viremia, and serum biochemical values were obtained from 16 DENV-2-inoculated, treated and untreated; four received only CLQ and one mock-infected Aotus monkeys. Monkey serum samples (day 0–10 post-inoculation) were assayed by reverse transcription polymerase chain reaction and Cytometric Bead Array for determination of viremia and inflammatory cytokines, respectively. Additionally, body temperature and activity levels were determined. In the present work, CLQ was effective on replication of DENV-2 in Aotus monkeys; a time viremia reduction was observed compared with the controls. The concentration of tumor necrosis factor alpha and interferon gamma in the serum of the animals had a statistically significant reduction in the groups treated with CLQ after infection compared with the controls. A significant decrease in systemic levels of the liver enzyme aspartate aminotransferase (AST) was also observed in the animals treated with CLQ after infection compared with the controls. These results suggest that CLQ interferes in DENV-2 replication in Aotus monkeys.",,"['Farias, Kleber Juvenal Silva', 'Machado, Paula Renata Lima', 'Muniz, José Augusto Pereira Carneiro', 'Imbeloni, Aline Amaral', 'da Fonseca, Benedito Antônio Lopes']",,,,
,PMC,Modification of the Hemagglutinin Cleavage Site Allows Indirect Activation of Avian Influenza Virus H9N2 by Bacterial Staphylokinase,http://dx.doi.org/10.1016/j.virol.2015.03.023,PMC4461493,,,"Influenza H9N2 is considered to be a low pathogenicity avian influenza (LPAI) virus that commonly infects avian species and can also infect humans. In 1996, the influenza virus, A/chicken/Korea/MS96-CE6/1996/H9N2 (MS96) was isolated from an outbreak in multiple farms in South Korea that resulted in upwards of 30% mortality in infected chickens, with the virus infecting a number of extrapulmonary tissues, indicating internal spread. However, in experimental infections, complete recovery of specific pathogen free (SPF) chickens occurred. Such a discrepancy indicated an alternative pathway for MS96 virus to gain virulence in farmed chickens. A key determinant of influenza pathogenesis is the susceptibility of the viral hemagglutinin (HA) to proteolytic cleavage/activation. Here, we identified that an amino acid substitution, Ser to Tyr found at the P2 position of the MS96 HA cleavage site optimizes cleavage by the protease plasmin (Pm). Importantly, we identified that certain Staphylococcus sp. are able to cleave and activate MS96 HA by activating plasminogen (Plg) to plasmin by use of a virulence factor, staphylokinase. Overall, these studies provide an in-vitro mechanism for bacterially mediated enhancement of influenza activation, and allow insight into the microbiological mechanisms underlying the avian influenza H9N2 outbreak in Korea in1996.",,"['Tse, Longping V.', 'Whittaker, Gary R.']",,,,
,PMC,Viral quasispecies,http://dx.doi.org/10.1016/j.virol.2015.03.022,PMC4826558,,,"New generation sequencing is greatly expanding the capacity to examine the composition of mutant spectra of viral quasispecies in infected cells and host organisms. Here we review recent progress in the understanding of quasispecies dynamics, notably the occurrence of intra-mutant spectrum interactions, and implications of fitness landscapes for virus adaptation and de-adaptation. Complementation or interference can be established among components of the same mutant spectrum, dependent on the mutational status of the ensemble. Replicative fitness relates to an optimal mutant spectrum that provides the molecular basis for phenotypic flexibility, with implications for antiviral therapy. The biological impact of viral fitness renders particularly relevant the capacity of new generation sequencing to establish viral fitness landscapes. Progress with experimental model systems is becoming an important asset to understand virus behavior in the more complex environments faced during natural infections.",,"['Andino, Raul', 'Domingo, Esteban']",,,,
,PMC,"Isolation and molecular characterization of nephropathic infectious bronchitis virus isolates of Gujarat state, India",http://dx.doi.org/10.1007/s13337-015-0248-x,PMC4585062,,,"Infectious bronchitis (IB) is a common, highly contagious, acute, and economically important viral disease of chickens caused by Infectious bronchitis virus (IBV, sp. Avian coronavirus). Five pooled tissue suspensions of 50 layer birds and one reference Massachusetts vaccine strain were inoculated into specific pathogen free (SPF) chicken egg for isolation of IBV. Reverse-transcription polymerase chain reaction (RT-PCR) was carried out using post inoculated allontoic fluid to amplify the spike (S) glycoprotein of S1 subunit of IBV. All the eggs inoculated with five pooled tissue samples and vaccine sample showed dwarfing and curling of SPF embryos indicative of IBV. All the five samples and the vaccine sample produced the expected amplicons of 466 bp by RT-PCR. The sequencing of five isolates revealed that all the five sequences were 99.09–100 % similar among themselves and showed 99.10–100 % nucleotide identity with the vaccine strain. On multiple sequence alignment it was found that our isolates were more similar at S1 subunit nucleotide level with the reference Ma5 and H120 vaccine strains than the reference Mass41 strain. The sequences of Anand isolates revealed further genetic changes in the circulating IBV in comparison to previous isolate of Gujarat as well as higher differences with the strains isolated in other states showing substantial changes at genetic level in Indian IBV isolates, which may partially explain the increasing incidences of IB in the country in spite of the vaccination. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13337-015-0248-x) contains supplementary material, which is available to authorized users.",,"['Patel, B. H.', 'Bhimani, M. P.', 'Bhanderi, B. B.', 'Jhala, M. K.']",,,,
,PMC,FcγRIIB prevents Inflammatory Type I Interferon Production from pDCs during a Viral Memory Response,http://dx.doi.org/10.4049/jimmunol.1401296,PMC4820833,,,"The type I interferon (IFNα) response is crucial for viral clearance during primary viral infections. Plasmacytoid dendritic cells are important early responders during systemic viral infections and, in some cases, the sole producers of IFNα. However, their role in IFNα production during memory responses is unclear. We found that IFNα production is absent during a murine viral memory response despite colocalization of virus and pDCs to the splenic marginal zone. The absence of interferon was dependent on circulating antibody, and reversed by the transgenic expression of the activating human FcγRIIA receptor on pDCs. Furthermore, FcγRIIB was required for Sendai Virus immune complex (SeV IC) uptake by splenic pDCs in vitro and internalization via FcγRIIb prevented cargo from accessing TLR signaling endosomes. Thus, pDCs bind viral immune complexes via FcγRIIB, and prevent IFNα production in vivo during viral memory responses. This antibody-dependent, IFNα regulation maybe an important mechanism by which the potentially deleterious effects of IFNα are prevented during a secondary infection.",,"['Flores, Marcella', 'Chew, Claude', 'Tyan, Kevin', 'Huang, Wu Qing', 'Salem, Aliasger', 'Clynes, Raphael']",,,,
,PMC,Social Media as a Sensor of Air Quality and Public Response in China,http://dx.doi.org/10.2196/jmir.3875,PMC4400579,25831020,CC BY,"BACKGROUND: Recent studies have demonstrated the utility of social media data sources for a wide range of public health goals, including disease surveillance, mental health trends, and health perceptions and sentiment. Most such research has focused on English-language social media for the task of disease surveillance. OBJECTIVE: We investigated the value of Chinese social media for monitoring air quality trends and related public perceptions and response. The goal was to determine if this data is suitable for learning actionable information about pollution levels and public response. METHODS: We mined a collection of 93 million messages from Sina Weibo, China’s largest microblogging service. We experimented with different filters to identify messages relevant to air quality, based on keyword matching and topic modeling. We evaluated the reliability of the data filters by comparing message volume per city to air particle pollution rates obtained from the Chinese government for 74 cities. Additionally, we performed a qualitative study of the content of pollution-related messages by coding a sample of 170 messages for relevance to air quality, and whether the message included details such as a reactive behavior or a health concern. RESULTS: The volume of pollution-related messages is highly correlated with particle pollution levels, with Pearson correlation values up to .718 (n=74, P<.001). Our qualitative results found that 67.1% (114/170) of messages were relevant to air quality and of those, 78.9% (90/114) were a firsthand report. Of firsthand reports, 28% (32/90) indicated a reactive behavior and 19% (17/90) expressed a health concern. Additionally, 3 messages of 170 requested that action be taken to improve quality. CONCLUSIONS: We have found quantitatively that message volume in Sina Weibo is indicative of true particle pollution levels, and we have found qualitatively that messages contain rich details including perceptions, behaviors, and self-reported health effects. Social media data can augment existing air pollution surveillance data, especially perception and health-related data that traditionally requires expensive surveys or interviews.",2015 Mar 26,"['Wang, Shiliang', 'Paul, Michael J', 'Dredze, Mark']",J Med Internet Res,,,
,PMC,Nuclear Proteins Hijacked by Mammalian Cytoplasmic Plus Strand RNA Viruses,http://dx.doi.org/10.1016/j.virol.2015.03.001,PMC4426963,,,"Plus strand RNA viruses that replicate in the cytoplasm face challenges in supporting the numerous biosynthetic functions required for replication and propagation. Most of these viruses are genetically simple and rely heavily on co-opting cellular proteins, particularly cellular RNA-binding proteins, into new roles for support of virus infection at the level of virus-specific translation, and building RNA replication complexes. In the course of infectious cycles many nuclear-cytoplasmic shuttling proteins of mostly nuclear distribution are detained in the cytoplasm by viruses and re-purposed for their own gain. Many mammalian viruses hijack a common group of the same factors. This review summarizes recent gains in our knowledge of how cytoplasmic RNA viruses use these co-opted host nuclear factors in new functional roles supporting virus translation and virus RNA replication and common themes employed between different virus groups.",,"Lloyd, Richard E.",,,,
,PMC,"International Health Regulations (2005) facilitate communication for in-flight contacts of a Middle East respiratory syndrome case, Hong Kong Special Administrative Region, 2014",http://dx.doi.org/10.2471/WPSAR.2015.6.1.002,PMC4410106,,,"The International Health Regulations (IHR) (2005) require World Health Organization Member States to notify events fulfilling two of four criteria: (1) serious public health impact; (2) unusual or unexpected event; (3) significant risk of international spread; or (4) significant risk of international travel or trade restrictions.(1) In-flight transmission of infections like severe acute respiratory syndrome is well documented.(2) With the enormous amount of air travel today, the risk of increasing in-flight transmission and subsequent international spread of infections are increasing. Prompt notification and information sharing under the IHR mechanism is critical for effective contact tracing and prompt control measures. We report on a case of in-flight exposure to an infection with significant public health risks that was successfully resolved using IHR (2005) guidelines.",,"['Kwok-ming, Poon', 'Miu-ling, Wong', 'Yiu-hong, Leung', 'Ka-wai, Sin', 'Liza, To May-kei', 'Shuk-kwan, Chuang']",,,,
,PMC,Middle East Respiratory Syndrome Coronavirus: Another Zoonotic Betacoronavirus Causing SARS-Like Disease,http://dx.doi.org/10.1128/CMR.00102-14,PMC4402954,,,"The source of the severe acute respiratory syndrome (SARS) epidemic was traced to wildlife market civets and ultimately to bats. Subsequent hunting for novel coronaviruses (CoVs) led to the discovery of two additional human and over 40 animal CoVs, including the prototype lineage C betacoronaviruses, Tylonycteris bat CoV HKU4 and Pipistrellus bat CoV HKU5; these are phylogenetically closely related to the Middle East respiratory syndrome (MERS) CoV, which has affected more than 1,000 patients with over 35% fatality since its emergence in 2012. All primary cases of MERS are epidemiologically linked to the Middle East. Some of these patients had contacted camels which shed virus and/or had positive serology. Most secondary cases are related to health care-associated clusters. The disease is especially severe in elderly men with comorbidities. Clinical severity may be related to MERS-CoV's ability to infect a broad range of cells with DPP4 expression, evade the host innate immune response, and induce cytokine dysregulation. Reverse transcription-PCR on respiratory and/or extrapulmonary specimens rapidly establishes diagnosis. Supportive treatment with extracorporeal membrane oxygenation and dialysis is often required in patients with organ failure. Antivirals with potent in vitro activities include neutralizing monoclonal antibodies, antiviral peptides, interferons, mycophenolic acid, and lopinavir. They should be evaluated in suitable animal models before clinical trials. Developing an effective camel MERS-CoV vaccine and implementing appropriate infection control measures may control the continuing epidemic.",,"['Chan, Jasper F. W.', 'Lau, Susanna K. P.', 'To, Kelvin K. W.', 'Cheng, Vincent C. C.', 'Woo, Patrick C. Y.', 'Yuen, Kwok-Yung']",,,,
,PMC,Murine Norovirus Replication Induces G(0)/G(1) Cell Cycle Arrest in Asynchronously Growing Cells,http://dx.doi.org/10.1128/JVI.03673-14,PMC4442456,,,"Many viruses replicate most efficiently in specific phases of the cell cycle, establishing or exploiting favorable conditions for viral replication, although little is known about the relationship between caliciviruses and the cell cycle. Microarray and Western blot analysis of murine norovirus 1 (MNV-1)-infected cells showed changes in cyclin transcript and protein levels indicative of a G(1) phase arrest. Cell cycle analysis confirmed that MNV-1 infection caused a prolonging of the G(1) phase and an accumulation of cells in the G(0)/G(1) phase. The accumulation in G(0)/G(1) phase was caused by a reduction in cell cycle progression through the G(1)/S restriction point, with MNV-1-infected cells released from a G(1) arrest showing reduced cell cycle progression compared to mock-infected cells. MNV-1 replication was compared in populations of cells synchronized into specific cell cycle phases and in asynchronously growing cells. Cells actively progressing through the G(1) phase had a 2-fold or higher increase in virus progeny and capsid protein expression over cells in other phases of the cell cycle or in unsynchronized populations. These findings suggest that MNV-1 infection leads to prolonging of the G(1) phase and a reduction in S phase entry in host cells, establishing favorable conditions for viral protein production and viral replication. There is limited information on the interactions between noroviruses and the cell cycle, and this observation of increased replication in the G(1) phase may be representative of other members of the Caliciviridae. IMPORTANCE Noroviruses have proven recalcitrant to growth in cell culture, limiting our understanding of the interaction between these viruses and the infected cell. In this study, we used the cell-culturable MNV-1 to show that infection of murine macrophages affects the G(1)/S cell cycle phase transition, leading to an arrest in cell cycle progression and an accumulation of cells in the G(0)/G(1) phase. Furthermore, we show that MNV replication is enhanced in the G(1) phase compared to other stages of the cell cycle. Manipulating the cell cycle or adapting to cell cycle responses of the host cell is a mechanism to enhance virus replication. To the best of our knowledge, this is the first report of a norovirus interacting with the host cell cycle and exploiting the favorable conditions of the G(0)/G(1) phase for RNA virus replication.",,"['Davies, Colin', 'Brown, Chris M.', 'Westphal, Dana', 'Ward, Joanna M.', 'Ward, Vernon K.']",,,,
,PMC,Asymptomatic Middle East Respiratory Syndrome Coronavirus Infection in Rabbits,http://dx.doi.org/10.1128/JVI.00661-15,PMC4442453,,,"The ability of Middle East respiratory syndrome coronavirus (MERS-CoV) to infect small animal species may be restricted given the fact that mice, ferrets, and hamsters were shown to resist MERS-CoV infection. We inoculated rabbits with MERS-CoV. Although virus was detected in the lungs, neither significant histopathological changes nor clinical symptoms were observed. Infectious virus, however, was excreted from the upper respiratory tract, indicating a potential route of MERS-CoV transmission in some animal species.",,"['Haagmans, Bart L.', 'van den Brand, Judith M. A.', 'Provacia, Lisette B.', 'Raj, V. Stalin', 'Stittelaar, Koert J.', 'Getu, Sarah', 'de Waal, Leon', 'Bestebroer, Theo M.', 'van Amerongen, Geert', 'Verjans, Georges M. G. M.', 'Fouchier, Ron A. M.', 'Smits, Saskia L.', 'Kuiken, Thijs', 'Osterhaus, Albert D. M. E.']",,,,
,PMC,Dissection of Amino-Terminal Functional Domains of Murine Coronavirus Nonstructural Protein 3,http://dx.doi.org/10.1128/JVI.00197-15,PMC4442451,,,"Coronaviruses, the largest RNA viruses, have a complex program of RNA synthesis that entails genome replication and transcription of subgenomic mRNAs. RNA synthesis by the prototype coronavirus mouse hepatitis virus (MHV) is carried out by a replicase-transcriptase composed of 16 nonstructural protein (nsp) subunits. Among these, nsp3 is the largest and the first to be inserted into the endoplasmic reticulum. nsp3 comprises multiple structural domains, including two papain-like proteases (PLPs) and a highly conserved ADP-ribose-1″-phosphatase (ADRP) macrodomain. We have previously shown that the ubiquitin-like domain at the amino terminus of nsp3 is essential and participates in a critical interaction with the viral nucleocapsid protein early in infection. In the current study, we exploited atypical expression schemes to uncouple PLP1 from the processing of nsp1 and nsp2 in order to investigate the requirements of nsp3 domains for viral RNA synthesis. In the first strategy, a mutant was created in which replicase polyprotein translation initiated with nsp3, thereby establishing that complete elimination of nsp1 and nsp2 does not abolish MHV viability. In the second strategy, a picornavirus autoprocessing element was used to separate a truncated nsp1 from nsp3. This provided a platform for further dissection of amino-terminal domains of nsp3. From this, we found that catalytic mutation of PLP1 or complete deletion of PLP1 and the adjacent ADRP domain was tolerated by the virus. These results showed that neither the PLP1 domain nor the ADRP domain of nsp3 provides integral activities essential for coronavirus genomic or subgenomic RNA synthesis. IMPORTANCE The largest component of the coronavirus replicase-transcriptase complex, nsp3, contains multiple modules, many of which do not have clearly defined functions in genome replication or transcription. These domains may play direct roles in RNA synthesis, or they may have evolved for other purposes, such as to combat host innate immunity. We initiated a dissection of MHV nsp3 aimed at identifying those activities or structures in this huge molecule that are essential to replicase activity. We found that both PLP1 and ADRP could be entirely deleted, provided that the requirement for proteolytic processing by PLP1 was offset by an alternative mechanism. This demonstrated that neither PLP1 nor ADRP plays an essential role in coronavirus RNA synthesis.",,"['Hurst-Hess, Kelley R.', 'Kuo, Lili', 'Masters, Paul S.']",,,,
,PMC,Function of the Herpes Simplex Virus 1 Small Capsid Protein VP26 Is Regulated by Phosphorylation at a Specific Site,http://dx.doi.org/10.1128/JVI.00547-15,PMC4442450,,,"Replacement of the herpes simplex virus 1 small capsid protein VP26 phosphorylation site Thr-111 with alanine reduced viral replication and neurovirulence to levels observed with the VP26 null mutation. This mutation reduced VP26 expression and mislocalized VP26 and its binding partner, the major capsid protein VP5, in the nucleus. VP5 mislocalization was also observed with the VP26 null mutation. Thus, we postulate that phosphorylation of VP26 at Thr-111 regulates VP26 function in vitro and in vivo.",,"['Kobayashi, Ryosuke', 'Kato, Akihisa', 'Oda, Shinya', 'Koyanagi, Naoto', 'Oyama, Masaaki', 'Kozuka-Hata, Hiroko', 'Arii, Jun', 'Kawaguchi, Yasushi']",,,,
,PMC,The Glycoprotein Precursor Gene of Junin Virus Determines the Virulence of the Romero Strain and the Attenuation of the Candid #1 Strain in a Representative Animal Model of Argentine Hemorrhagic Fever,http://dx.doi.org/10.1128/JVI.00104-15,PMC4442433,,,"The New World arenavirus Junin virus (JUNV) is the causative agent of Argentine hemorrhagic fever (AHF), a potentially deadly disease endemic to central regions of Argentina. The live-attenuated Candid #1 (Can) strain of JUNV is currently used to vaccinate the human population at risk. However, the mechanism of attenuation of this strain is still largely unknown. Therefore, the identification and functional characterization of viral genetic determinants dictating JUNV virulence or attenuation would significantly improve the understanding of the mechanisms underlying AHF and facilitate the development of novel, more effective, and safer vaccines. Here, we utilized a reverse genetics approach to generate recombinant JUNV (rJUNV) strains encoding different gene combinations of the pathogenic Romero (Rom) and attenuated Can strains of JUNV. All strains of rJUNV exhibited in vitro growth kinetics similar to those of their parental counterparts. Analysis of virulence of the rJUNV in a guinea pig model of lethal infection that closely reproduces the features of AHF identified the envelope glycoproteins (GPs) as the major determinants of pathogenesis and attenuation of JUNV. Accordingly, rJUNV strains expressing the full-length GPs of Rom and Can exhibited virulent and attenuated phenotypes, respectively, in guinea pigs. Mutation F427I in the transmembrane region of JUNV envelope glycoprotein GP2 has been shown to attenuate the neurovirulence of JUNV in suckling mice. We document that in the guinea pig model of AHF, mutation F427I in GP2 is also highly attenuating but insufficient to prevent virus dissemination and development of mild clinical and pathological symptoms, indicating that complete attenuation of JUNV requires additional mutations present in Can glycoprotein precursor (GPC). IMPORTANCE Development of antiviral strategies against viral hemorrhagic fevers, including AHF, is one of the top priorities within the Implementation Plan of the U.S. Department of Health and Human Services Public Health Emergency Medical Countermeasures Enterprise. Live-attenuated Candid #1 strain, derived from the 44th mouse brain passage of the prototype XJ strain of JUNV, has been demonstrated to be safe, immunogenic, and highly protective and is currently licensed for human use in Argentina. However, the bases for the attenuated phenotype of Candid #1 have not been established. Therefore, the identification and functional characterization of viral genetic factors implicated in JUNV pathogenesis and attenuation would significantly improve the understanding of the molecular mechanisms underlying AHF and facilitate the development of novel antiviral strategies.",,"['Seregin, Alexey V.', 'Yun, Nadezhda E.', 'Miller, Milagros', 'Aronson, Judith', 'Smith, Jennifer K.', 'Walker, Aida G.', 'Smith, Jeanon N.', 'Huang, Cheng', 'Manning, John T.', 'de la Torre, Juan C.', 'Paessler, Slobodan']",,,,
,PMC,"Crystal structure of the C-terminal 2’,5’-phosphodiesterase domain of group A rotavirus protein VP3",http://dx.doi.org/10.1002/prot.24794,PMC5068548,,,"In response to viral infections, the mammalian innate immune system induces the production of the second messenger 2’-5’ oligoadenylate (2–5A) to activate latent ribonuclease L (RNase L) that restricts viral replication and promotes apoptosis. A subset of rotaviruses and coronaviruses encode 2’,5’-phosphodiesterase enzymes that hydrolyze 2–5A, thereby inhibiting RNase L activation. We report the crystal structure of the 2’,5’-phosphodiesterase domain of group A rotavirus protein VP3 at 1.39 Å resolution. The structure exhibits a 2H phosphoesterase fold and reveals conserved active site residues, providing insights into the mechanism of 2–5A degradation in viral evasion of host innate immunity.",,"['Brandmann, Tobias', 'Jinek, Martin']",,,,
,PMC,Self-Assembly of a 9-Residue Amyloid-Forming Peptide Fragment of SARS Corona Virus E-protein: Mechanism of Self Aggregation and Amyloid-Inhibition of hIAPP,http://dx.doi.org/10.1021/acs.biochem.5b00061,PMC4903029,,,"Molecular self-assembly, a phenomenon widely observed in nature, has been exploited through organic molecules, proteins, DNA and peptides to study complex biological systems. These self-assembly systems may also be used in understanding the molecular and structural biology which can inspire the design and synthesis of increasingly complex biomaterials. Specifically, use of these building blocks to investigate protein folding and misfolding has been of particular value since it can provide tremendous insights into peptide aggregation related to a variety of protein misfolding diseases, or amyloid diseases (e.g. Alzheimer’s disease, Parkinson’s disease, type-II diabetes). Herein, the self-assembly of TK9, a 9 residue peptide of the extra membrane C-terminal tail of the SARS Corona virus envelope, and its variants were characterized through biophysical, spectroscopic and simulated studies, and it was confirmed that the structure of these peptides influence their aggregation propensity, hence, mimicking amyloid proteins. TK9, which forms a beta-sheet rich fibril, contains a key sequence motif that may be critical for beta-sheet formation, thus making it an interesting system to study amyloid fibrillation. TK9 aggregates were further examined through simulations to evaluate the possible intra- and inter peptide interactions at the molecular level. These self-assembly peptides can also serve as amyloid inhibitors through hydrophobic and electrophilic recognition interactions. Our results show that TK9 inhibits the fibrillation of hIAPP, a 37 amino acid peptide implicated in the pathology of type-II diabetes. Thus, biophysical and NMR experimental results have revealed a molecular level understanding of peptide folding events, as well as the inhibition of amyloid-protein aggregation are reported.",,"['Ghosh, Anirban', 'Pithadia, Amit S.', 'Bhat, Jyotsna', 'Bera, Supriyo', 'Midya, Anupam', 'Fierke, Carol A.', 'Ramamoorthy, Ayyalusamy', 'Bhunia, Anirban']",,,,
,PMC,CD13 Restricts TLR4 Endocytic Signal Transduction in Inflammation,http://dx.doi.org/10.4049/jimmunol.1403133,PMC4402264,,,"Dysregulation of the innate immune response underlies numerous pathological conditions. The Toll-like Receptor 4 (TLR4) is the prototypical sensor of infection or injury that orchestrates the innate response via sequential activation of both cell-surface and endocytic signaling pathways that trigger distinct downstream consequences. CD14 binds and delivers LPS to TLR4 and has been identified as a positive regulator of TLR4 signal transduction. It is logical that negative regulators of this process also exist to maintain the critical balance required for fighting infection, healing damaged tissue and resolving inflammation. We showed that CD13 negatively modulates receptor-mediated Ag uptake in dendritic cells to control T-cell activation in adaptive immunity. Here we report that myeloid CD13 governs internalization of TLR4 and subsequent innate signaling cascades, activating IRF-3 independently of CD14. CD13 is co-internalized with TLR4, CD14 and dynamin into Rab5(+) early endosomes upon LPS treatment. Importantly, in response to TLR4 ligands HMGB1 and LPS, pIRF-3 activation and transcription of its target genes is enhanced in CD13(KO) DCs while TLR4 surface signaling remains unaffected, resulting in a skewed inflammatory response. This finding is physiologically relevant as ischemic injury in vivo provoked identical TLR4 responses. Finally, CD13(KO) mice showed significantly enhanced IFNβ-mediated signal transduction via JAK-STAT, escalating iNOS transcription levels and promoting accumulation of oxidative stress mediators and tissue injury. Mechanistically, inflammatory activation of macrophages upregulates CD13 expression and CD13 and TLR4 co-immunoprecipitate. Therefore, CD13 negatively regulates TLR4 signaling, thereby balancing the innate response by maintaining the inflammatory equilibrium critical to innate immune regulation.",,"['Ghosh, Mallika', 'Subramani, Jaganathan', 'Rahman, M. Mamunur', 'Shapiro, Linda H.']",,,,
,PMC,Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS,http://dx.doi.org/10.1152/ajplung.00380.2014,PMC4451399,,,"The early sequence of events leading to the development of the acute respiratory distress syndrome (ARDS) in patients with sepsis remains inadequately understood. The purpose of this study was to identify changes in gene expression early in the course of illness, when mechanisms of injury may provide the most relevant treatment and prognostic targets. We collected whole blood RNA in critically ill patients admitted from the Emergency Department to the intensive care unit within 24 h of admission at a tertiary care center. Whole genome expression was compared in patients with sepsis and ARDS to patients with sepsis alone. We selected genes with >1 log(2) fold change and false discovery rate <0.25, determined their significance in the literature, and performed pathway analysis. Several genes were upregulated in 29 patients with sepsis with ARDS compared with 28 patients with sepsis alone. The most differentially expressed genes included key mediators of the initial neutrophil response to infection: olfactomedin 4, lipocalin 2, CD24, and bactericidal/permeability-increasing protein. These gene expression differences withstood adjustment for age, sex, study batch, white blood cell count, and presence of pneumonia or aspiration. Pathway analysis demonstrated overrepresentation of genes involved in known respiratory and infection pathways. These data indicate that several neutrophil-related pathways may be involved in the early pathogenesis of sepsis-related ARDS. In addition, identifiable gene expression differences occurring early in the course of sepsis-related ARDS may further elucidate understanding of the neutrophil-related mechanisms in progression to ARDS.",,"['Kangelaris, Kirsten Neudoerffer', 'Prakash, Arun', 'Liu, Kathleen D.', 'Aouizerat, Bradley', 'Woodruff, Prescott G.', 'Erle, David J.', 'Rogers, Angela', 'Seeley, Eric J.', 'Chu, Jeffrey', 'Liu, Tom', 'Osterberg-Deiss, Thomas', 'Zhuo, Hanjing', 'Matthay, Michael A.', 'Calfee, Carolyn S.']",,,,
,PMC,Evaluation of eluents for the recovery of an enveloped virus from hands by whole-hand sampling,http://dx.doi.org/10.1111/jam.12777,PMC4594860,,,"AIMS: The objective of this research is to evaluate eluents for recovery of an enveloped bacteriophage, Φ6, using whole-hand sampling. METHODS AND RESULTS: Virus was applied to the hands of volunteers and sampled by the glove juice method with 1.5% beef extract (BE), phosphate buffered saline (PBS), 0.01 and 0.1% Tween 80, tryptic soy broth (TSB), and 9% NaCl. Each volunteer underwent multiple rounds application and hand sampling. Mean log(10) virus loss across trials was 2.6 for BE, 2.8 for PBS, 2.4 for TSB, 3.8 for NaCl, 3.0 for 0.1% Tween 80, and 2.9 for 0.01% Tween 80. Within each volunteer, there was a decline in viral loss from the first to last trial. CONCLUSIONS: These eluents can recover Φ6 from hands with ~2-3 log(10) loss, comparable to recoveries previously reported for influenza. Protein and detergent-based eluents may have similar recoveries, but recovery may still vary across repeated sampling. SIGNIFICANCE AND IMPACT: Based on current work, protein-based eluents such as beef extract can maximize recovery of enveloped viruses during hand sampling, providing methods for evaluating survival and transmission of enveloped viruses on hands. Further exploration is needed of the effect of repeated sampling on recovery from whole-hand sampling.",,"['Casanova, Lisa M.', 'Weaver, Scott R.']",,,,
,PMC,"Structure-Guided Design and Optimization of Dipeptidyl Inhibitors of Norovirus 3CL Protease. Structure-Activity Relationships and Biochemical, X-ray Crystallographic, Cell-Based, and In Vivo Studies",http://dx.doi.org/10.1021/jm5019934,PMC4484267,,,"Norovirus infection constitutes the primary cause of acute viral gastroenteritis. There are currently no vaccines or norovirus-specific antiviral therapeutics available for the management of norovirus infection. Norovirus 3C-like protease is essential for viral replication, consequently, inhibition of this enzyme is a fruitful avenue of investigation that may lead to the emergence of anti-norovirus therapeutics. We describe herein the optimization of dipeptidyl inhibitors of norovirus 3C-like protease using iterative SAR, X-ray crystallographic, and enzyme and cell-based studies. We also demonstrate herein in vivo efficacy of an inhibitor using the murine model of norovirus infection.",,"['Kankanamalage, Anushka C. Galasiti', 'Kim, Yunjeong', 'Weerawarna, Pathum M.', 'Uy, Roxanne Adeline Z.', 'Damalanka, Vishnu C.', 'Mandadapu, Sivakoteswara Rao', 'Alliston, Kevin R.', 'Mehzabeen, Nurjahan', 'Battaile, Kevin P.', 'Lovell, Scott', 'Chang, Kyeong-Ok', 'Groutas, William C.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00457-15,PMC4442363,,,,,,,,,
,PMC,Household animal and human medicine use and animal husbandry practices in rural Bangladesh: risk factors for emerging zoonotic disease and antibiotic resistance,http://dx.doi.org/10.1111/zph.12186,PMC4575599,,,"Animal antimicrobial use and husbandry practices increase risk of emerging zoonotic disease and antibiotic resistance. We surveyed 700 households to elicit information on human and animal medicine use and husbandry practices. Households that owned livestock (n=265/459, 57.7%) reported using animal treatments 630 times during the previous 6 months; 57.6% obtained medicines, including antibiotics, from drug-sellers. Government animal health care providers were rarely visited (9.7 %), respondents more often sought animal health care from pharmacies and village doctors (70.6% and 11.9% respectively), citing the latter two as less costly and more successful based on past performance. Animal husbandry practices that could promote the transmission of microbes from animals to humans included: the proximity of chickens to humans (50.1% of households reported that the chickens slept in the bedroom); the shared use of natural bodies of water for human and animal bathing (78.3%); the use of livestock waste as fertilizer (60.9%); and gender roles that dictate that females are the primary care takers of poultry and children (62.8%). In the absence of an effective animal health care system, villagers must depend on local animal health care practitioners for treatment of their animals. Suboptimal use of antimicrobials coupled with unhygienic animal husbandry practices are important risk factors for emerging zoonotic disease and resistant pathogens.",,"['Roess, Amira A.', 'Winch, Peter J.', 'Akhter, Afsana', 'Afroz, Dilara', 'Ali, Nabeel A.', 'Shah, Rashed', 'Begum, Nazma', 'Seraji, Habibur Rahman', 'Arifeen, Shams El', 'Darmstadt, Gary L.', 'Baqui, Abdullah H.']",,,,
,PMC,Development and Validation of a Rapid Immunochromatographic Assay for Detection of Middle East Respiratory Syndrome Coronavirus Antigen in Dromedary Camels,http://dx.doi.org/10.1128/JCM.03096-14,PMC4365254,,,"We present here a rapid immunochromatographic assay for the detection of Middle East respiratory syndrome coronavirus (MERS-CoV) antigen in the nasal swabs of dromedary camels. The assay is based on the detection of MERS-CoV nucleocapsid protein in a short time frame using highly selective monoclonal antibodies at room temperature. The relative sensitivity and specificity of the assay were found to be 93.90% and 100%, respectively, compared to that of the UpE and open reading frame 1A (Orf1A) real-time reverse transcriptase PCR (RT-PCR). The results suggest that the assay developed here is a useful tool for the rapid diagnosis and epidemiological surveillance of MERS-CoV infection in dromedary camels.",,"['Song, Daesub', 'Ha, Gunwoo', 'Serhan, Wissam', 'Eltahir, Yassir', 'Yusof, Mohammed', 'Hashem, Farouq', 'Elsayed, Elsaeid', 'Marzoug, Bahaaeldin', 'Abdelazim, Assem', 'Al Muhairi, Salama']",,,,
,PMC,Efficient Isolation of Swine Influenza Viruses by Age-Targeted Specimen Collection,http://dx.doi.org/10.1128/JCM.02941-14,PMC4365228,,,"The control of swine influenza virus (SIV) infection is paramount for increasing the productivity of pig farming and minimizing the threat of pandemic outbreaks. Thus, SIV surveillance should be conducted by region and on a regular basis. Here, we established a microneutralization assay specific for SIV seroprevalence surveillance by using reporter gene-expressing recombinant influenza viruses. Growth-based SIV seroprevalence revealed that most sows and piglets were positive for neutralizing antibodies against influenza viruses. In contrast, the 90-day-old growing pigs exhibited limited neutralizing activity in their sera, suggesting that this particular age of population is most susceptible to SIV infection and thus is an ideal age group for SIV isolation. From nasal swab specimens of healthy pigs in this age population, we were able to isolate SIVs at a higher incidence (5.3%) than those of previous reports. Nucleotide sequencing and phylogenetic analysis of the hemagglutinin (HA) genes revealed that the isolated SIVs have circulated and evolved in pigs but not have been recently introduced from humans, implying that a large number of SIV lineages may remain “undiscovered” in the global porcine populations. We propose that the 90-day-old growing pig-targeted nasal swab collection presented in this study facilitates global SIV surveillance and contributes to the detection and control of SIV infection.",,"['Ozawa, Makoto', 'Matsuu, Aya', 'Yonezawa, Kouki', 'Igarashi, Manabu', 'Okuya, Kosuke', 'Kawabata, Toshiko', 'Ito, Kimihito', 'Tsukiyama-Kohara, Kyoko', 'Taneno, Akira', 'Deguchi, Eisaburo']",,,,
,PMC,Clinical Relevance of Multiple Respiratory Virus Detection in Adult Patients with Acute Respiratory Illness,http://dx.doi.org/10.1128/JCM.03298-14,PMC4365199,,,"Because increasing numbers of nasopharyngeal swab specimens from adult patients with acute respiratory illness (ARI) are being tested by respiratory virus (RV) multiplex reverse transcriptase PCR (RVM-RT-PCR), multiple RV detection (MRVD) is being encountered more frequently. However, the clinical relevance of MRVD in adult patients has rarely been evaluated. The clinical characteristics of hospitalized adult patients with ARI and MRVD by RVM-RT-PCR tests were compared to those of patients with single RV detection (SRVD) during a single year at a tertiary care center. MRVD was observed in 26 of the 190 adult patients (13.7%). The patients with MRVD had a higher incidence of chronic lung disease than the patients with SRVD (34.6% versus 15.9%, crude odds ratio [OR] = 2.81, 95% confidence interval [CI] = 1.13 to 6.98, P = 0.03). Although the former were more likely than the latter to receive mechanical ventilation (19.2% versus 6.7%, crude OR = 3.31, 95% CI = 1.05 to 10.47, P = 0.049), the length of hospital stay (median, 7 versus 6.5 days; P = 0.66), and the in-hospital mortality rate (7.7% versus 4.3%, crude OR = 1.87, 95% CI = 0.37 to 9.53, P = 0.35) were not different between the two groups. In multivariate analysis, chronic lung disease was associated with MRVD (adjusted OR = 3.08, 95% CI = 1.12 to 8.46, P = 0.03). In summary, it was not uncommon to encounter adult patients with ARI and MRVD by RVM-RT-PCR tests of nasopharyngeal swab specimens. MRVD was associated with chronic lung disease rather than the severity of the ARI.",,"['Choi, Seong-Ho', 'Chung, Jin-Won', 'Kim, Hye Ryoun']",,,,
,PMC,Receptor Usage and Cell Entry of Porcine Epidemic Diarrhea Coronavirus,http://dx.doi.org/10.1128/JVI.00430-15,PMC4442452,,,"Porcine epidemic diarrhea coronavirus (PEDV) has significantly damaged America's pork industry. Here we investigate the receptor usage and cell entry of PEDV. PEDV recognizes protein receptor aminopeptidase N from pig and human and sugar coreceptor N-acetylneuraminic acid. Moreover, PEDV infects cells from pig, human, monkey, and bat. These results support the idea of bats as an evolutionary origin for PEDV, implicate PEDV as a potential threat to other species, and suggest antiviral strategies to control its spread.",,"['Liu, Chang', 'Tang, Jian', 'Ma, Yuanmei', 'Liang, Xueya', 'Yang, Yang', 'Peng, Guiqing', 'Qi, Qianqian', 'Jiang, Shibo', 'Li, Jianrong', 'Du, Lanying', 'Li, Fang']",,,,
,PMC,Passive Immunotherapy with Dromedary Immune Serum in an Experimental Animal Model for Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/JVI.00446-15,PMC4442417,,,"Middle East respiratory syndrome (MERS) is a highly lethal pulmonary infection. Serum from convalescent MERS patients may provide some benefit but is not readily available. In contrast, nearly all camels in the Middle East have been infected with MERS-CoV. Here, we show that sera obtained from MERS-immune camels augment the kinetics of MERS-CoV clearance and reduce the severity of pathological changes in infected lungs, with efficacy proportional to the titer of MERS-CoV-neutralizing serum antibody. IMPORTANCE Middle East respiratory syndrome, caused by a coronavirus, is highly lethal, with a case fatality rate of 35 to 40%. No specific therapy is available, and care is generally supportive. One promising approach is passive administration of sera from convalescent human MERS patients or other animals to exposed or infected patients. The vast majority of, if not all, camels in the Middle East have been infected with MERS-CoV, and some contain high titers of antibody to the virus. Here, we show that this antibody is protective if delivered either prophylactically or therapeutically to mice infected with MERS-CoV, indicating that this may be a useful intervention in infected patients.",,"['Zhao, Jincun', 'Perera, Ranawaka A. P. M.', 'Kayali, Ghazi', 'Meyerholz, David', 'Perlman, Stanley', 'Peiris, Malik']",,,,
,PMC,Inhibitor recognition specificity of MERS-CoV papain-like protease differs from that of SARS-CoV,http://dx.doi.org/10.1021/cb500917m,PMC4845099,,,"The Middle East Respiratory Syndrome coronavirus (MERS-CoV) papain-like protease (PLpro) blocking loop 2 (BL2) structure differs significantly from that of SARS-CoV PLpro, where it has been proven to play a crucial role in SARS-CoV PLpro inhibitor binding. Four SARS-CoV PLpro lead inhibitors were tested against MERS-CoV PLpro, none of which were effective against MERS-CoV PLpro. Structure and sequence alignments revealed that two residues, Y269 and Q270, responsible for inhibitor binding to SARS-CoV PLpro were replaced by T274 and A275 in MERS-CoV PLpro, making critical binding interactions difficult to form for similar types of inhibitors. High-throughput screening (HTS) of 25,000 compounds against both PLpro enzymes identified a small fragment-like noncovalent dual inhibitor. Mode of inhibition studies by enzyme kinetics and competition surface plasmon resonance (SPR) analyses suggested that this compound acts as a competitive inhibitor with an IC(50) of 6 µM against MERS-CoV PLpro, indicating that it binds to the active site, whereas it acts as an allosteric inhibitor against SARS-CoV PLpro with an IC(50) of 11 µM. These results raised the possibility that inhibitor recognition specificity of MERS-CoV PLpro may differ from that of SARS-CoV PLpro. In addition, inhibitory activity of this compound was selective for SARS-CoV and MERS-CoV PLpro enzymes over two human homologues, the ubiquitin C-terminal hydrolases 1 and 3 (hUCH-L1 and hUCH-L3).",,"['Lee, Hyun', 'Lei, Hao', 'Santarsiero, Bernard D.', 'Gatuz, Joseph L.', 'Cao, Shuyi', 'Rice, Amy J.', 'Patel, Kavankumar', 'Szypulinski, Michael Z.', 'Ojeda, Isabel', 'Ghosh, Arun K.', 'Johnson, Michael E.']",,,,
,PMC,Development of Animal Models Against Emerging Coronaviruses: From SARS to MERS coronavirus,http://dx.doi.org/10.1016/j.virol.2015.02.030,PMC4793273,,,"Two novel coronaviruses have emerged to cause severe disease in humans. While bats may be the primary reservoir for both viruses, SARS coronavirus (SARS-CoV) likely crossed into humans from civets in China, and MERS coronavirus (MERS-CoV) has been transmitted from camels in the Middle East. Unlike SARS-CoV that resolved within a year, continued introductions of MERS-CoV present an on-going public health threat. Animal models are needed to evaluate countermeasures against emerging viruses. With SARS-CoV, several animal species were permissive to infection. In contrast, most laboratory animals are refractory or only semi-permissive to infection with MERS-CoV. This host-range restriction is largely determined by sequence heterogeneity in the MERS-CoV receptor. We describe animal models developed to study coronaviruses, with a focus on host-range restriction at the level of the viral receptor and discuss approaches to consider in developing a model to evaluate countermeasures against MERS-CoV.",,"['Sutton, Troy C', 'Subbarao, Kanta']",,,,
,PMC,Biomechanics analysis for the treatment of ischemic necrosis of the femoral head by using an interior supporting system,,PMC4443217,,,"Objective: This work aims to perform a biomechanical test to evaluate the effect of interior supporting system and tantalum rod in simulating the treatment of ischemic necrosis of the femoral head. Method: Three models were established: control group (group A), interior supporting system group (group B), and tantalum rod group (group C). Step-by-step loading was applied on the top of the femoral head until femoral head damage occurs by using the testing machine of the material test system. Strain and maximum load were applied until the femoral head collapses. The damage to the trochanteric fossa, femur calcar, and greater trochanter were compared. Results: (1) The strain on the trochanteric fossa shows the following order: group C > group A and group B (P < 0.05). No significant difference was observed among groups for the other parts (P > 0.05). (2) The maximum load in group B is larger than that in groups A and C (P < 0.05). No significant difference in the maximum load was observed among the three groups when the femoral head was destroyed. Conclusions: The compression strain and bearing load of the femoral head are close to normal after placement of an interior supporting system and tantalum rod. The interior supporting system helps prevent femoral head collapse.",,"['Xiao, Dongmin', 'Ye, Ming', 'Li, Xiong', 'Wu, Hong', 'Zhong, Chi']",,,,
,PMC,MiR-592 inhibited cell proliferation of human colorectal cancer cells by suppressing of CCND3 expression,,PMC4443074,,,"Accumulating evidence shows that microRNA (miRNA) is frequently associated with multiple kinds of human cancers, including colorectal cancer (CRC). Previous studies have shown that miR-592 play critical roles in cancer cell biological processes. However, the function of miR-592 in CRC remains largely unknown. In the present study, we investigated the miR-592’s role in cell proliferation of colorectal cancer. MiR-592 expression was markedly down-regulated in CRC tissues and CRC cells. Overexpression of miR-592 reduced the proliferation and anchorage-independent growth of CRC cells. Furthermore, bioinformatics analysis further revealed CCND3, a putative tumor promoter, was found to be a potential target of miR-592 in CRC. The dual-luciferase reporter gene assay results showed that CCND3 was a direct target of miR-592. Ectopic expression of miR-592 led to down-regulation of CCND3 protein, which resulted in the down-regulation of phosphorylated retinoblastoma (p-Rb). In functional assays, CCND3-silenced in miR-592-in-transfected SW48 cells have positive effect to suppress cell proliferation, suggesting that direct CCND3 suppression is required for miR-592-induced cell proliferation of CRC. We conclude that miR-592 can regulate CCND3 and function as a tumor suppressor in CRC. Therefore, miR-592 represents a potential anti-onco-miR and serves as a useful therapeutic agent for miRNA-based CRC therapy.",,"['Liu, Zhehui', 'Wu, Ruiqin', 'Li, Guanzeng', 'Sun, Peng', 'Xu, Qinghua', 'Liu, Zhimin']",,,,
,PMC,Functional and molecular evidence for expression of the renin angiotensin system and ADAM17-mediated ACE2 shedding in COS7 cells,http://dx.doi.org/10.1152/ajpcell.00247.2014,PMC4420792,,,"The renin angiotensin system (RAS) plays a vital role in the regulation of the cardiovascular and renal functions. COS7 is a robust and easily transfectable cell line derived from the kidney of the African green monkey, Cercopithecus aethiops. The aims of this study were to 1) demonstrate the presence of an endogenous and functional RAS in COS7, and 2) investigate the role of a disintegrin and metalloproteinase-17 (ADAM17) in the ectodomain shedding of angiotensin converting enzyme-2 (ACE2). Reverse transcription coupled to gene-specific polymerase chain reaction demonstrated expression of ACE, ACE2, angiotensin II type 1 receptor (AT(1)R), and renin at the transcript levels in total RNA cell extracts. Western blot and immunohistochemistry identified ACE (60 kDa), ACE2 (75 kDa), AT(1)R (43 kDa), renin (41 kDa), and ADAM17 (130 kDa) in COS7. At the functional level, a sensitive and selective mass spectrometric approach detected endogenous renin, ACE, and ACE2 activities. ANG-(1–7) formation (m/z 899) from the natural substrate ANG II (m/z 1,046) was detected in lysates and media. COS7 cells stably expressing shRNA constructs directed against endogenous ADAM17 showed reduced ACE2 shedding into the media. This is the first study demonstrating endogenous expression of the RAS and ADAM17 in the widely used COS7 cell line and its utility to study ectodomain shedding of ACE2 mediated by ADAM17 in vitro. The transfectable nature of this cell line makes it an attractive cell model for studying the molecular, functional, and pharmacological properties of the renal RAS.",,"['Grobe, Nadja', 'Di Fulvio, Mauricio', 'Kashkari, Nada', 'Chodavarapu, Harshita', 'Somineni, Hari K.', 'Singh, Richa', 'Elased, Khalid M.']",,,,
,PMC,Genomic profiling of host responses to Lassa virus: therapeutic potential from primate to man,http://dx.doi.org/10.2217/fvl.15.1,PMC4383259,,,"Lassa virus infection elicits distinctive changes in host gene expression and metabolism. We focus on changes in host gene expression that may be biomarkers that discriminate individual pathogens or may help to provide a prognosis for disease. In addition to assessing mRNA changes, functional studies are also needed to discriminate causes of disease from mechanisms of host resistance. Host responses that drive pathogenesis are likely to be targets for prevention or therapy. Host responses to Lassa or its related arenaviruses have been monitored in cell culture, in animal models of hemorrhagic fever, in Lassa-infected nonhuman primates and, to a limited extent, in infected human beings. Here, we describe results from those studies and discuss potential targets for reducing virus replication and mitigating disease.",,"['Zapata, Juan C', 'Salvato, Maria S']",,,,
,PMC,Modeling infectious disease dynamics in the complex landscape of global health,http://dx.doi.org/10.1126/science.aaa4339,PMC4445966,,,"Despite some notable successes in the control of infectious diseases, transmissible pathogens still pose an enormous threat to human and animal health. The ecological and evolutionary dynamics of infections play out on a wide range of interconnected temporal, organizational and spatial scales, which even within a single pathogen often span hours to months, cellular to ecosystem levels, and local to pandemic spread. Some pathogens are directly transmitted between individuals of a single species, while others circulate among multiple hosts, need arthropod vectors, or can survive in environmental reservoirs. Many factors, including increasing antimicrobial resistance, increased human connectivity, and dynamic human behavior, raise prevention and control from formerly national to international issues. In the face of this complexity, mathematical models offer essential tools for synthesizing information to understand epidemiological patterns, and for developing the quantitative evidence base for decision-making in global health.",,"['Heesterbeek, Hans', 'Anderson, Roy', 'Andreasen, Viggo', 'Bansal, Shweta', 'De Angelis, Daniela', 'Dye, Chris', 'Eames, Ken', 'Edmunds, John', 'Frost, Simon', 'Funk, Sebastian', 'Hollingsworth, Deirdre', 'House, Thomas', 'Isham, Valerie', 'Klepac, Petra', 'Lessler, Justin', 'Lloyd-Smith, James', 'Metcalf, Jessica', 'Mollison, Denis', 'Pellis, Lorenzo', 'Pulliam, Juliet', 'Roberts, Mick', 'Viboud, Cecile', None]",,,,
,PMC,Clinical disease due to enterovirus D68 in adult hematologic malignancy patients and hematopoietic cell transplant recipients,http://dx.doi.org/10.1182/blood-2014-12-616516,PMC4357580,,,"The United States Centers for Disease Control and Prevention reported over 1000 cases of severe respiratory disease in pediatric patients associated with enterovirus D68 (EV-D68) in the fall of 2014. We sought to identify and define the clinical burden of disease due to EV-D68 in adult patients with hematologic malignancy or undergoing hematopoietic cell transplant (HCT). Real-time reverse-transcriptase polymerase chain reaction (PCR) for EV-D68 was performed on all respiratory samples positive for human rhinovirus (HRV) or negative for all respiratory viruses by a laboratory-developed respiratory viral PCR panel from August 11, 2014, to November 7, 2014. Presumptive cases were defined as those with an EV-D68 PCR cycle threshold (CT) at least 4 cycles lower than the HRV CT for HRV-positive samples or any EV-D68 CT value for HRV-negative samples. Sequencing of a 150-bp fragment of the 5′ noncoding region confirmed EV-D68 in 16 of 506 respiratory samples. Eight patients had a history of hematologic malignancy, and 6 of these had undergone HCT. Presentation ranged from mild upper respiratory symptoms to respiratory failure. EV-D68 can infect adult patients with hematologic malignancy and HCT recipients and may be associated with severe respiratory disease. Current commercial diagnostic assays cannot differentiate EV-D68 from other enteroviruses or HRV, and improved rapid diagnostic tools are needed.",,"['Waghmare, Alpana', 'Pergam, Steven A.', 'Jerome, Keith R.', 'Englund, Janet A.', 'Boeckh, Michael', 'Kuypers, Jane']",,,,
,PMC,Ethical and Practical Considerations in Providing Critical Care to Patients With Ebola Virus Disease,http://dx.doi.org/10.1378/chest.15-0278,PMC4451704,,,"Infectious disease epidemics in the past have given rise to psychologic and emotional responses among health-care workers (HCWs), stemming from fear of infection during patient care. Early experiences in the AIDS epidemic provide an example where fear of contagion resulted in differential treatment of patients infected with HIV. However, with a deeper understanding of AIDS pathogenesis and treatment, fear and discrimination diminished. Parallels exist between early experiences with AIDS and the present outbreak of Ebola virus disease in West Africa, particularly regarding discussions of medical futility in seriously ill patients. We provide a historical perspective on HCWs’ risk of infection during the provision of CPR, discuss physicians’ duty to treat in the face of perceived or actual HCW risk, and, finally, present the protocols implemented at the National Institutes of Health to reduce HCW risk while providing lifesaving and life-sustaining care.",,"['Torabi-Parizi, Parizad', 'Davey, Richard T.', 'Suffredini, Anthony F.', 'Chertow, Daniel S.']",,,,
,PMC,Creosote bush lignans for human disease treatment and prevention: Perspectives on combination therapy,http://dx.doi.org/10.1016/j.jtcme.2014.11.024,PMC4488564,26151022,CC BY-NC-ND,"The medicinal properties of the most successful plant in the deserts of the western hemisphere, the creosote bush (Larrea tridentata), are evidenced by the long traditional usage of the plants by the Native Americans Indian tribes in Southwestern North America and the Amerindians from South America. The plant is rich in simple bisphenyl lignans and tricyclic lignans known as cyclolignans. These compounds are responsible for many of the pharmacological activities of extracts of the plants. Some of these activities, namely antiherpes, antioxidant, antifungal, and anti-inflammatory, were known a century ago. Only recently have further studies revealed other crucial activities of the same plant molecules as powerful agents against human immunodeficiency virus, human papillomavirus, cancer, neurodegenerative diseases, and symptoms of aging. Molecular mechanisms underlying the antiviral and anticancer activities have been elucidated and involve the inhibition of SP1 dependent gene transcription. This review summarizes the recent findings on creosote bush lignans. We introduce the concept of a cocktail of safe well-characterized natural products from the creosote bush that would represent a bridge between oriental herbal medicines and Western drug-based therapies.",2015 Mar 12,"['Gnabre, John', 'Bates, Robert', 'Huang, Ru Chih']",J Tradit Complement Med,,,
,PMC,Timing is everything: Fine-tuned molecular machines orchestrate paramyxovirus entry,http://dx.doi.org/10.1016/j.virol.2015.02.037,PMC4424121,,,"The Paramyxoviridae include some of the great and ubiquitous disease-causing viruses of humans and animals. In most paramyxoviruses, two viral membrane glycoproteins, fusion protein (F) and receptor binding protein (HN, H or G) mediate a concerted process of recognition of host cell surface molecules followed by fusion of viral and cellular membranes, resulting in viral nucleocapsid entry into the cytoplasm. The interactions between the F and HN, H or G viral glycoproteins and host molecules are critical in determining host range, virulence and spread of these viruses. Recently, atomic structures, together with biochemical and biophysical studies, have provided major insights into how these two viral glycoproteins successfully interact with host receptors on cellular membranes and initiate the membrane fusion process to gain entry into cells. These studies highlight the conserved core mechanisms of paramyxovirus entry that provide the fundamental basis for rational anti-viral drug design and vaccine development.",,"['Bose, Sayantan', 'Jardetzky, Theodore S.', 'Lamb, Robert A.']",,,,
,PMC,Biochemical Characterization of Recombinant Enterovirus 71 3C Protease with Fluorogenic Model Peptide Substrates and Development of a Biochemical Assay,http://dx.doi.org/10.1128/AAC.04698-14,PMC4356770,,,"Enterovirus 71 (EV71), a primary pathogen of hand, foot, and mouth disease (HFMD), affects primarily infants and children. Currently, there are no effective drugs against HFMD. EV71 3C protease performs multiple tasks in the viral replication, which makes it an ideal antiviral target. We synthesized a small set of fluorogenic model peptides derived from cleavage sites of EV71 polyprotein and examined their efficiencies of cleavage by EV71 3C protease. The novel peptide P08 [(2-(N-methylamino)benzoyl) (NMA)-IEALFQGPPK(DNP)FR] was determined to be the most efficiently cleaved by EV71 3C protease, with a kinetic constant k(cat)/K(m) of 11.8 ± 0.82 mM(−1) min(−1). Compared with literature reports, P08 gave significant improvement in the signal/background ratio, which makes it an attractive substrate for assay development. A Molecular dynamics simulation study elaborated the interactions between substrate P08 and EV71 3C protease. Arg39, which is located at the bottom of the S2 pocket of EV71 3C protease, may participate in the proteolysis process of substrates. With an aim to evaluate EV71 3C protease inhibitors, a reliable and robust biochemical assay with a Z′ factor of 0.87 ± 0.05 was developed. A novel compound (compound 3) (50% inhibitory concentration [IC(50)] = 1.89 ± 0.25 μM) was discovered using this assay, which effectively suppressed the proliferation of EV 71 (strain Fuyang) in rhabdomyosarcoma (RD) cells with a highly selective index (50% effective concentration [EC(50)] = 4.54 ± 0.51 μM; 50% cytotoxic concentration [CC(50)] > 100 μM). This fast and efficient assay for lead discovery and optimization provides an ideal platform for anti-EV71 drug development targeting 3C protease.",,"['Shang, Luqing', 'Zhang, Shumei', 'Yang, Xi', 'Sun, Jixue', 'Li, Linfeng', 'Cui, Zhengjie', 'He, Qiuhong', 'Guo, Yu', 'Sun, Yuna', 'Yin, Zheng']",,,,
,PMC,Cellular 5′-3′ mRNA Exonuclease Xrn1 Controls Double-stranded RNA Accumulation and Anti-Viral Responses,http://dx.doi.org/10.1016/j.chom.2015.02.003,PMC4826345,,,"By accelerating global mRNA decay, many viruses impair host protein synthesis, limiting host defenses and stimulating virus mRNA translation. Vaccinia virus (VacV) encodes two decapping enzymes (D9, D10) that remove protective 5′ caps on mRNAs, presumably generating substrates for degradation by the host exonuclease Xrn1. Surprisingly, we find VacV infection of Xrn1-depleted cells inhibits protein synthesis, compromising virus growth. These effects are aggravated by D9-deficiency and dependent upon a virus transcription factor required for intermediate and late mRNA biogenesis. Considerable double-stranded RNA (dsRNA) accumulation in Xrn1-depleted cells is accompanied by activation of host dsRNA-responsive defenses controlled by PKR and 2′-5′-oligoadenylate synthetase (OAS), which respectively inactivate the translation initiation factor eIF2 and stimulate RNA cleavage by RNase L. This proceeds despite VacV-encoded PKR and RNase L antagonists being present. Moreover, Xrn1-depletion sensitizes uninfected cells to dsRNA treatment. Thus, Xrn1 is a cellular factor regulating dsRNA accumulation and dsRNA-responsive innate immune effectors.",,"['Burgess, Hannah M.', 'Mohr, Ian']",,,,
,PMC,Computational Approaches to Influenza Surveillance: Beyond Timeliness,http://dx.doi.org/10.1016/j.chom.2015.02.004,PMC4492472,,,"Several digital data sources and systems have been advanced for use in augmenting traditional influenza surveillance systems. Although timeliness is one of the main advantage of these tools, there are several other recognizable uses and potential impact of these systems on the public and global public health.",,"['Nsoesie, Elaine O.', 'Brownstein, John S.']",,,,
,PMC,Poxvirus Decapping Enzymes Enhance Virulence by Preventing the Accumulation of dsRNA and the Induction of Innate Antiviral Responses,http://dx.doi.org/10.1016/j.chom.2015.02.002,PMC4359750,,,"Poxvirus replication involves synthesis of double stranded RNA (dsRNA), which can trigger antiviral responses by inducing phosphorylation-mediated activation of protein kinase R (PKR) and stimulating 2’5’-oligoadenylate synthetase (OAS). PKR inactivates the translation initiation factor eIF2α via phosphorylation, while OAS induces the endonuclease RNase L to degrade RNA. We show that poxvirus decapping enzymes D9 and D10, which remove caps from mRNAs, inhibit these antiviral responses by preventing dsRNA accumulation. Catalytic site mutations of D9 and D10, but not of either enzyme alone, halt vaccinia virus late protein synthesis and inhibit virus replication. Infection with the D9-D10 mutant was accompanied by massive mRNA reduction, cleavage of ribosomal RNA and phosphorylation of PKR and eIF2α that correlated with a ~15-fold increase in dsRNA compared to wild-type virus. Additionally, mouse studies show extreme attenuation of the mutant virus. Thus, vaccinia virus decapping, in addition to targeting mRNAs for degradation, prevents dsRNA accumulation and anti-viral responses.",,"['Liu, Shin-Wu', 'Katsafanas, George C.', 'Liu, Ruikang', 'Wyatt, Linda S.', 'Moss, Bernard']",,,,
,PMC,"Suicide in the Global Chinese Aging Population: A Review of Risk and Protective Factors, Consequences, and Interventions",http://dx.doi.org/10.14336/AD.2014.0223,PMC4365956,,,"As one of the leading causes of death around the world, suicide is a global public health threat. In the Chinese population, suicides constitute one-fifth of all recorded suicides in the world. Despite the factual data on suicide rates, the understanding of various causal factors behind suicide, including risk and protective factors and adverse health care, remained incomplete among the global Chinese aging population. To fill in the knowledge void, this paper reviews the epidemiology of suicide among Chinese older adults globally as well as explores the existing intervention strategies. Using the PRISMA statement, we performed a systematic review of exiting research on the topic, including studies describing suicide among Chinese older adults in communities outside of Asia. A literature search was conducted online by using both medical and social science data-bases. Our findings highlighted that elderly suicide in Chinese populations is significantly affected by the social, cultural, and familial contexts within which the individual lived prior to committing suicide. Reviewing such research indicated that while reducing risk factors may contribute to lowering suicides amongst Chinese older adults, measures to improve protective factors are also critical. Support through ongoing family and community care relationships is necessary to improve resilience in older adults and positive aging. Future longitudinal studies on the risk factors and protective factors, and adverse health consequences are called for to devise culturally and linguistically appropriate prevention and intervention programs in global Chinese aging populations.",,"['Dong, XinQi', 'Chang, E-Shien', 'Zeng, Ping', 'Simon, Melissa A.']",,,,
,PMC,Viral-associated glomerulopathies in children,http://dx.doi.org/10.1007/s00467-015-3057-y,PMC4581998,,,"Viral infections associate temporally with the onset of many glomerular diseases, particularly in children. In other cases of glomerulonephritis, when infection is clinically silent, viral syndromes can still be implicated as a trigger. However, strong evidence for viral causality in most glomerular disease is still lacking. While numerous case reports in children document the occurrence of specific forms of glomerular disease after seroconversion to a wide range of viruses, relatively few reports provide pathologic evidence of viral infection associated with glomerular lesions on kidney biopsy. Strong associations between hepatitis viruses and glomerular injury have been acknowledged in adults, but hepatitis C virus appears not to be an etiology in children. In the context of treating glomerular diseases, when diagnosed, the treatment of hepatitis B virus, cytomegalovirus and human immunodeficiency virus in children with membranoproliferative, membranous and collapsing glomerulopathy plays an important role. Otherwise, there is no evidence suggesting that the identification of a viral infection in a child with glomerulopathy should change the management of the infection or the glomerulonephritis. Therefore, additional research into this topic is very much needed.",,"Wenderfer, Scott E.",,,,
,PMC,Mechanisms of Innate Immune Evasion In Re-Emerging RNA Viruses,http://dx.doi.org/10.1016/j.coviro.2015.02.005,PMC4470747,,,"Recent outbreaks of Ebola, West Nile, Chikungunya, Middle Eastern Respiratory and other emerging/re-emerging RNA viruses continue to highlight the need to further understand the virus-host interactions that govern disease severity and infection outcome. As part of the early host antiviral defense, the innate immune system mediates pathogen recognition and initiation of potent antiviral programs that serve to limit virus replication and spread and activate adaptive immune responses. Concordantly, viral pathogens have evolved several strategies to counteract pathogen recognition and cell-intrinsic antiviral responses. In this Review, we highlight the major mechanisms of innate immune evasion by emerging and re-emerging RNA viruses, focusing on pathogens that pose significant risk to public health.",,"['Ma, Daphne Y.', 'Suthar, Mehul S.']",,,,
,PMC,Journal Watch,http://dx.doi.org/10.1177/1757177415572647,PMC5074169,,,,,"['Wigglesworth, Neil', 'Xuereb, Debbie']",,,,
,PMC,"Evolution and population genomics of the Lyme borreliosis pathogen, Borrelia burgdorferi",http://dx.doi.org/10.1016/j.tig.2015.02.006,PMC4380588,,,"Population genomic studies have the potential to address many unresolved questions about microbial pathogens by facilitating the identification of genes underlying ecologically important traits such as novel virulence factors and adaptations to humans or other host species. Additionally, this framework improves estimations of population demography and evolutionary history to accurately reconstruct recent epidemics and identify the molecular and environmental factors that resulted in the outbreak. The Lyme disease bacterium, Borrelia burgdorferi, exemplifies the power and promise of the application of population genomics to microbial pathogens. We discuss here the future of evolutionary studies in B.burgdorferi - focusing on the primary evolutionary forces of horizontal gene transfer, natural selection, and migration - as investigations transition from analyses of single genes to genomes.",,"['Seifert, Stephanie N', 'Khatchikian, Camilo E.', 'Zhou, Wei', 'Brisson, Dustin']",,,,
,PMC,Impact of human mobility on the periodicities and mechanisms underlying measles dynamics,http://dx.doi.org/10.1098/rsif.2014.1317,PMC4345498,,,"Three main mechanisms determining the dynamics of measles have been described in the literature: invasion in disease-free lands leading to import-dependent outbreaks, switching between annual and biennial attractors driven by seasonality, and amplification of stochastic fluctuations close to the endemic equilibrium. Here, we study the importance of the three mechanisms using a detailed geographical description of human mobility. We perform individual-based simulations of an SIR model using a gridded description of human settlements on top of which we implement human mobility according to the radiation model. Parallel computation permits detailed simulations of large areas. Focusing our research on the British Isles, we show that human mobility has an impact on the periodicity of measles outbreaks. Depending on the level of mobility, we observe at the global level multi-annual, annual or biennial cycles. The periodicity observed globally, however, differs from the local epidemic cycles: different locations show different mechanisms at work depending on both population size and mobility. As a result, the periodicities observed locally depend on the interplay between the local population size and human mobility.",,"['Marguta, Ramona', 'Parisi, Andrea']",,,,
,PMC,Modelling the propagation of social response during a disease outbreak,http://dx.doi.org/10.1098/rsif.2014.1105,PMC4345477,,,"Epidemic trajectories and associated social responses vary widely between populations, with severe reactions sometimes observed. When confronted with fatal or novel pathogens, people exhibit a variety of behaviours from anxiety to hoarding of medical supplies, overwhelming medical infrastructure and rioting. We developed a coupled network approach to understanding and predicting social response. We couple the disease spread and panic spread processes and model them through local interactions between agents. The social contagion process depends on the prevalence of the disease, its perceived risk and a global media signal. We verify the model by analysing the spread of disease and social response during the 2009 H1N1 outbreak in Mexico City and 2003 severe acute respiratory syndrome and 2009 H1N1 outbreaks in Hong Kong, accurately predicting population-level behaviour. This kind of empirically validated model is critical to exploring strategies for public health intervention, increasing our ability to anticipate the response to infectious disease outbreaks.",,"['Fast, Shannon M.', 'González, Marta C.', 'Wilson, James M.', 'Markuzon, Natasha']",,,,
,PMC,Dengue: what it is and why there is more,http://dx.doi.org/10.1007/s11434-015-0756-5,PMC4666553,,,"In 2014, China experienced the worst outbreak of dengue fever in the last decade with over 40,000 dengue cases including six deaths by the end of October. As one of the “neglected” tropical diseases, dengue is affecting substantially increasing number of people and proportion of global population due to factors including globalization, human settlement, and possibly climate change. Here, the authors summarized the most recent data about dengue outbreaks in China and reviewed the global trend of dengue epidemiology. Future directions for dengue surveillance, control and prevention are also introduced.",,"['Li, Yuan', 'Wu, Shuyu']",,,,
,PMC,RIG-I in RNA virus recognition,http://dx.doi.org/10.1016/j.virol.2015.02.017,PMC4424084,,,"Antiviral immunity is initiated upon host recognition of viral products via non-self molecular patterns known as pathogen-associated molecular patterns (PAMPs). Such recognition initiates signaling cascades that induce intracellular innate immune defenses and an inflammatory response that facilitates development of the acquired immune response. The retinoic acid-inducible gene I (RIG-I) and the RIG-I-like receptor (RLR) protein family are key cytoplasmic pathogen recognition receptors that are implicated in the recognition of viruses across genera and virus families, including functioning as major sensors of RNA viruses, and promoting recognition of some DNA viruses. RIG-I, the charter member of the RLR family, is activated upon binding to PAMP RNA. Activated RIG-I signals by interacting with the adapter protein MAVS leading to a signaling cascade that activates the transcription factors IRF3 and NF-κB. These actions induce the expression of antiviral gene products and the production of type I and III interferons that lead to an antiviral state in the infected cell and surrounding tissue. RIG-I signaling is essential for the control of infection by many RNA viruses. Recently, RIG-I crosstalk with other pathogen recognition receptors and components of the inflammasome has been described. In this review, we discuss the current knowledge regarding the role of RIG-I in recognition of a variety of virus families and its role in programming the adaptive immune response through cross-talk with parallel arms of the innate immune system, including how RIG-I can be leveraged for antiviral therapy.",,"['Kell, Alison M.', 'Gale, Michael']",,,,
,PMC,A Metagenomics and Case-Control Study To Identify Viruses Associated with Bovine Respiratory Disease,http://dx.doi.org/10.1128/JVI.00064-15,PMC4442534,,,"Bovine respiratory disease (BRD) is a common health problem for both dairy and beef cattle, resulting in significant economic loses. In order to identify viruses associated with BRD, we used a metagenomics approach to enrich and sequence viral nucleic acids in the nasal swabs of 50 young dairy cattle with symptoms of BRD. Following deep sequencing, de novo assembly, and translated protein sequence similarity searches, numerous known and previously uncharacterized viruses were identified. Bovine adenovirus 3, bovine adeno-associated virus, bovine influenza D virus, bovine parvovirus 2, bovine herpesvirus 6, bovine rhinitis A virus, and multiple genotypes of bovine rhinitis B virus were identified. The genomes of a previously uncharacterized astrovirus and picobirnaviruses were also partially or fully sequenced. Using real-time PCR, the rates of detection of the eight viruses that generated the most reads were compared for the nasal secretions of 50 animals with BRD versus 50 location-matched healthy control animals. Viruses were detected in 68% of BRD-affected animals versus 16% of healthy control animals. Thirty-eight percent of sick animals versus 8% of controls were infected with multiple respiratory viruses. Significantly associated with BRD were bovine adenovirus 3 (P < 0.0001), bovine rhinitis A virus (P = 0.005), and the recently described bovine influenza D virus (P = 0.006), which were detected either alone or in combination in 62% of animals with BRD. A metagenomics and real-time PCR detection approach in carefully matched cases and controls can provide a rapid means to identify viruses associated with a complex disease, paving the way for further confirmatory tests and ultimately to effective intervention strategies. IMPORTANCE Bovine respiratory disease is the most economically important disease affecting the cattle industry, whose complex root causes include environmental, genetics, and infectious factors. Using an unbiased metagenomics approach, we characterized the viruses in respiratory secretions from BRD cases and identified known and previously uncharacterized viruses belonging to seven viral families. Using a case-control format with location-matched animals, we compared the rates of viral detection and identified 3 viruses associated with severe BRD signs. Combining a metagenomics and case-control format can provide candidate pathogens associated with complex infectious diseases and inform further studies aimed at reducing their impact.",,"['Ng, Terry Fei Fan', 'Kondov, Nikola O.', 'Deng, Xutao', 'Van Eenennaam, Alison', 'Neibergs, Holly L.', 'Delwart, Eric']",,,,
,PMC,"Dynamic Interaction of Stress Granules, DDX3X, and IKK-α Mediates Multiple Functions in Hepatitis C Virus Infection",http://dx.doi.org/10.1128/JVI.03197-14,PMC4442532,,,"The ubiquitous ATP-dependent RNA helicase DDX3X is involved in many cellular functions, including innate immunity, and is a pivotal host factor for hepatitis C virus (HCV) infection. Recently, we showed that DDX3X specifically recognizes the HCV 3′ untranslated region (UTR), leading to the activation of IKK-α and a cascade of lipogenic signaling to facilitate lipid droplet biogenesis and viral assembly (Q. Li, V. Pene, S. Krishnamurthy, H. Cha, and T. J. Liang, Nat Med 19:722–729, 2013, http://dx.doi.org/10.1038/nm.3190). The interaction of DDX3X with HCV core protein seems to be dispensable for its proviral role. In this study, through systematic imaging and biochemical and virologic approaches, we identified a dynamic association between DDX3X and various cellular compartments and viral elements mediating multiple functions of DDX3X in productive HCV infection. Upon HCV infection, the HCV 3′UTR interacts with DDX3X and IKK-α, which redistribute to speckle-like cytoplasmic structures shown to be stress granules (SGs). As viral proteins accumulate in infected cells, DDX3X granules together with SG-associated proteins redistribute and colocalize with HCV core protein around lipid droplets (LDs). IKK-α, however, does not relocate to the LD but translocates to the nucleus. In HCV-infected cells, various HCV nonstructural proteins also interact or colocalize with DDX3X in close proximity to SGs and LDs, consistent with the tight juxtaposition of the replication complex and the assembly site at the surface of LDs. Short interfering RNA (siRNA)-mediated silencing of DDX3X and multiple SG components markedly inhibits HCV infection. Our data suggest that DDX3X initiates a multifaceted cellular program involving dynamic associations with HCV RNA and proteins, IKK-α, SG, and LD surfaces for its crucial role in the HCV life cycle. IMPORTANCE DDX3X is a proviral host factor for HCV infection. Recently, we showed that DDX3X binds to the HCV 3′UTR, activating IKK-α and cellular lipogenesis to facilitate viral assembly (Q. Li et al., Nat Med 19:722–729, 2013, http://dx.doi.org/10.1038/nm.3190). Here, we report associations of DDX3X with various cellular compartments and viral elements that mediate its multiple functions in the HCV life cycle. Upon infection, the HCV 3′UTR redistributes DDX3X and IKK-α to speckle-like cytoplasmic structures shown to be SGs. Subsequently, interactions between DDX3X, SG, and HCV proteins facilitate the translocation of DDX3X-SG complexes to the LD surface. HCV nonstructural proteins are shown to colocalize with DDX3X in close proximity to SGs and LDs, consistent with the tight juxtaposition of the HCV replication complex and assembly site at the LD surface. Our data demonstrate that DDX3X initiates a multifaceted cellular program involving dynamic associations with HCV elements, IKK-α, SGs, and LDs for its critical role in HCV infection.",,"['Pène, Véronique', 'Li, Qisheng', 'Sodroski, Catherine', 'Hsu, Ching-Sheng', 'Liang, T. Jake']",,,,
,PMC,Functional Properties and Genetic Relatedness of the Fusion and Hemagglutinin-Neuraminidase Proteins of a Mumps Virus-Like Bat Virus,http://dx.doi.org/10.1128/JVI.03693-14,PMC4442385,,,"A bat virus with high phylogenetic relatedness to human mumps virus (MuV) was identified recently at the nucleic acid level. We analyzed the functional activities of the hemagglutinin-neuraminidase (HN) and the fusion (F) proteins of the bat virus (batMuV) and compared them to the respective proteins of a human isolate. Transfected cells expressing the F and HN proteins of batMuV were recognized by antibodies directed against these proteins of human MuV, indicating that both viruses are serologically related. Fusion, hemadsorption, and neuraminidase activities were demonstrated for batMuV, and either bat-derived protein could substitute for its human MuV counterpart in inducing syncytium formation when coexpressed in different mammalian cell lines, including chiropteran cells. Cells expressing batMuV glycoproteins were shown to have lower neuraminidase activity. The syncytia were smaller, and they were present in lower numbers than those observed after coexpression of the corresponding glycoproteins of a clinical isolate of MuV (hMuV). The phenotypic differences in the neuraminidase and fusion activity between the glycoproteins of batMuV and hMuV are explained by differences in the expression level of the HN and F proteins of the two viruses. In the case of the F protein, analysis of chimeric proteins revealed that the signal peptide of the bat MuV fusion protein is responsible for the lower surface expression. These results indicate that the surface glycoproteins of batMuV are serologically and functionally related to those of hMuV, raising the possibility of bats as a reservoir for interspecies transmission. IMPORTANCE The recently described MuV-like bat virus is unique among other recently identified human-like bat-associated viruses because of its high sequence homology (approximately 90% in most genes) to its human counterpart. Although it is not known if humans can be infected by batMuV, the antigenic relatedness between the bat and human forms of the virus suggests that humans carrying neutralizing antibodies against MuV are protected from infection by batMuV. The close functional relationship between MuV and batMuV is demonstrated by cooperation of the respective HN and F proteins to induce syncytium formation in heterologous expression studies. An interesting feature of the glycoproteins of batMuV is the downregulation of the fusion activity by the signal peptide of F, which has not been reported for other paramyxoviruses. These results are important contributions for risk assessment and for a better understanding of the replication strategy of batMuV.",,"['Krüger, Nadine', 'Hoffmann, Markus', 'Drexler, Jan Felix', 'Müller, Marcel Alexander', 'Corman, Victor Max', 'Sauder, Christian', 'Rubin, Steven', 'He, Biao', 'Örvell, Claes', 'Drosten, Christian', 'Herrler, Georg']",,,,
,PMC,Glutathione and multidrug resistance protein transporter mediate a self-propelled disposal of bismuth in human cells,http://dx.doi.org/10.1073/pnas.1421002112,PMC4371909,,,"Glutathione and multidrug resistance protein (MRP) play an important role on the metabolism of a variety of drugs. Bismuth drugs have been used to treat gastrointestinal disorder and Helicobacter pylori infection for decades without exerting acute toxicity. They were found to interact with a wide variety of biomolecules, but the major metabolic pathway remains unknown. For the first time (to our knowledge), we systematically and quantitatively studied the metabolism of bismuth in human cells. Our data demonstrated that over 90% of bismuth was passively absorbed, conjugated to glutathione, and transported into vesicles by MRP transporter. Mathematical modeling of the system reveals an interesting phenomenon. Passively absorbed bismuth consumes intracellular glutathione, which therefore activates de novo biosynthesis of glutathione. Reciprocally, sequestration by glutathione facilitates the passive uptake of bismuth and thus completes a self-sustaining positive feedback circle. This mechanism robustly removes bismuth from both intra- and extracellular space, protecting critical systems of human body from acute toxicity. It elucidates the selectivity of bismuth drugs between human and pathogens that lack of glutathione, such as Helicobacter pylori, opening new horizons for further drug development.",,"['Hong, Yifan', 'Lai, Yau-Tsz', 'Chan, Godfrey Chi-Fung', 'Sun, Hongzhe']",,,,
,PMC,"To translate, or not to translate: viral and host mRNA regulation by interferon-stimulated genes",http://dx.doi.org/10.1016/j.tcb.2015.02.001,PMC4441850,,,"Type I interferon (IFN) is one of the first lines of cellular defense against viral pathogens. As a result of IFN signaling, a wide array of IFN-stimulated gene (ISG) products is upregulated to target different stages of the viral life cycle. We review recent findings implicating a subset of ISGs in translational regulation of viral and host mRNAs. Translation inhibition is mediated either by binding to viral RNA or by disrupting physiological interactions or levels of the translation complex components. In addition, many of these ISGs localize to translationally silent cytoplasmic granules, such as stress granules and processing bodies, and intersect with the microRNA (miRNA)-mediated silencing pathway to regulate translation of cellular mRNAs.",,"['Li, Melody M. H.', 'MacDonald, Margaret R.', 'Rice, Charles M.']",,,,
,PMC,Towards the prophylactic and therapeutic use of human neutralizing monoclonal antibodies for Middle East respiratory syndrome coronavirus (MERS-CoV),http://dx.doi.org/10.3978/j.issn.2305-5839.2015.01.15,PMC4356854,,,,,"['Sakamoto, Seiichi', 'Tanaka, Hiroyuki', 'Morimoto, Satoshi']",,,,
,PMC,"AMMI Canada 2015 Annual Conference: Abstracts: April 16 – 18, 2015 • Charlottetown, Prince Edward Island",,PMC4419824,,,,,,,,,
,PMC,Nine challenges in modelling the emergence of novel pathogens,http://dx.doi.org/10.1016/j.epidem.2014.09.002,PMC4715032,25843380,CC BY,"Studying the emergence of novel infectious agents involves many processes spanning host species, spatial scales, and scientific disciplines. Mathematical models play an essential role in combining insights from these investigations and drawing robust inferences from field and experimental data. We describe nine challenges in modelling the emergence of novel pathogens, emphasizing the interface between models and data.",2015 Mar,"['Lloyd-Smith, James O.', 'Funk, Sebastian', 'McLean, Angela R.', 'Riley, Steven', 'Wood, James L.N.']",Epidemics,,,
,PMC,Analysis of potential changes in seriousness of influenza A and B viruses in Hong Kong from 2001 to 2011,http://dx.doi.org/10.1017/S0950268814001472,PMC4391961,,,"Continued monitoring of the seriousness of influenza viruses is a public health priority. We applied time series regression models to data on cardio-respiratory mortality rates in Hong Kong from 2001 through 2011. We used surveillance data on outpatient consultations for influenza-like illness, and laboratory detections of influenza types/subtypes to construct proxy measures of influenza activity. In the model we allowed the regression coefficients for influenza to drift over time, and adjusted for temperature and humidity. The regression coefficient for influenza A(H3N2) increased significantly in 2005. The regression coefficients for influenza A(H1N1) and B were relatively stable over the period. Our model suggested an increase in seriousness of A(H3N2) in 2005, the year after the appearance of the A/Fujian/411/2002(H3N2)-like virus when the drifted A/California/7/2004(H3N2)-like virus appeared. Ongoing monitoring of mortality and influenza activity could permit identification of future changes in seriousness of influenza virus infections.",,"['Wong, Jessica Y.', 'Wu, Peng', 'Goldstein, Edward', 'Lau, Eric H. Y.', 'Ip, Dennis K. M.', 'Wu, Joseph T.', 'Cowling, Benjamin J.']",,,,
,PMC,Identification and Management of Middle East Respiratory Syndrome,,PMC6363470,,,"Federal health care providers need to be vigilant to this new coronavirus from the Arabian Peninsula, not only to properly treat patients, but also to minimize the risk of exposure and transmission.",,"['Byrd, Ryland P.', 'Roy, Thomas M.']",,,,
,PMC,Immunology studies in non-human primate models of tuberculosis,http://dx.doi.org/10.1111/imr.12258,PMC4339213,,,"Non-human primates, primarily macaques, have been used to study tuberculosis for decades. However, in the last 15 years, this model has been refined substantially to allow careful investigations of the immune response and host-pathogen interactions in Mycobacterium tuberculosis infection. Low dose challenge with fully virulent strains in cynomolgus macaques result in the full clinical spectrum seen in humans, including latent and active infection. Reagents from humans are usually cross-reactive with macaques, further facilitating the use of this model system to study tuberculosis. Finally, macaques develop the spectrum of granuloma types seen in humans, providing a unique opportunity to investigate bacterial and host factors at the local (lung and lymph node) level. Here we review the past decade of immunology and pathology studies in macaque models of tuberculosis.",,"['Flynn, JoAnne L.', 'Gideon, Hannah P.', 'Mattila, Joshua T.', 'Lin, Philana Ling']",,,,
,PMC,Combined effect of tnf-α polymorphisms and hypoxia on steroid-induced osteonecrosis of femoral head,,PMC4440152,,,"Objective: Tumor necrosis factor (TNF)-α is a proinflammatory cytokine, some studies reported that TNF-α gene plays important role in the pathogenesis of SONFH. And the polymorphisms of TNF-α were presented as risk factors for steroid-induced osteonecrosis of the femoral head (SONFH). Meanwhile, various environment factors involve in the pathogenesis of SONFH. Our study aimed to investigate the interaction effect of TNF-α polymorphisms and hypoxia factor on SONFH. Methods: 120 patients with SONFH and 100 healthy people, matched with the cases on age and sex, participated in this study. DNA was extracted from all participants. According to previous studies, genotyping of TNF-α polymorphisms (rs1800629, rs1799964 and rs1800630) was tested with the method of PCR-RDB (Reverse Dot Blot). Environmental factors were also chose. Logistic regression analysis was used to analyze the interaction between TNF-α polymorphisms and environment factors on SONFH. Results: The polymorphisms of rs1800629 and rs1800630 were significantly associated with SONFH (OR: 3.70, 9.93). Patients with hypoxia history were found higher (65.00%) compared with the healthy controls (43.00%). For the person with hypoxic history, GG and AG+AA genotypes of rs1800629 could increase their risk to suffer SONFH (OR: 2.12, 3.78). If the patients with the variant genotypes of rs1800630 experienced hypoxia state, then the risk for SONFH increased 2.41 folds. Conclusion: We concluded that the onset of SONFH was influenced by TNF-α and hypoxia history. There existed strong interaction between TNF-α and hypoxia history.",,"['Liu, Yaosheng', 'Jiang, Weihao', 'Liu, Shubin', 'Su, Xiuyun', 'Zhou, Shiguo']",,,,
,PMC,A review of genetic methods and models for analysis of coronavirus-induced severe pneumonitis,http://dx.doi.org/10.1099/vir.0.069732-0,PMC4811657,,,"Coronaviruses (CoVs) have been studied for over 60 years, but have only recently gained notoriety as deadly human pathogens with the emergence of severe respiratory syndrome CoV and Middle East respiratory syndrome virus. The rapid emergence of these viruses has demonstrated the need for good models to study severe CoV respiratory infection and pathogenesis. There are, currently, different methods and models for the study of CoV disease. The available genetic methods for the study and evaluation of CoV genetics are reviewed here. There are several animal models, both mouse and alternative animals, for the study of severe CoV respiratory disease that have been examined, each with different pros and cons relative to the actual pathogenesis of the disease in humans. A current limitation of these models is that no animal model perfectly recapitulates the disease seen in humans. Through the review and analysis of the available disease models, investigators can employ the most appropriate available model to study various aspects of CoV pathogenesis and evaluate possible antiviral treatments that may potentially be successful in future treatment and prevention of severe CoV respiratory infections.",,"['McGruder, Brenna', 'Leibowitz, Julian L.']",,,,
,PMC,Hydroxychloroquine-Inhibited Dengue Virus Is Associated with Host Defense Machinery,http://dx.doi.org/10.1089/jir.2014.0038,PMC4350140,,,"Hydroxychloroquine (HCQ) is an antimalarial drug also used in treating autoimmune diseases. Its antiviral activity was demonstrated in restricting HIV infection in vitro; however, the clinical implications remain controversial. Infection with dengue virus (DENV) is a global public health problem, and we lack an antiviral drug for DENV. Here, we evaluated the anti-DENV potential of treatment with HCQ. Immunofluorescence assays demonstrated that HCQ could inhibit DENV serotype 1–4 infection in vitro. RT-qPCR analysis of HCQ-treated cells showed induced expression of interferon (IFN)-related antiviral proteins and certain inflammatory cytokines. Mechanistic study suggested that HCQ activated the innate immune signaling pathways of IFN-β, AP-1, and NFκB. Knocking down mitochondrial antiviral signaling protein (MAVS), inhibiting TANK binding kinase 1 (TBK1)/inhibitor-κB kinase ɛ (IKKɛ), and blocking type I IFN receptor reduced the efficiency of HCQ against DENV-2 infection. Furthermore, HCQ significantly induced cellular production of reactive oxygen species (ROS), which was involved in the host defense system. Suppression of ROS production attenuated the innate immune activation and anti-DENV-2 effect of HCQ. In summary, HCQ triggers the host defense machinery by inducing ROS- and MAVS-mediated innate immune activation against DENV infection and may be a candidate drug for DENV infection.",,"['Wang, Li-Fong', 'Lin, You-Sheng', 'Huang, Nan-Chieh', 'Yu, Chia-Yi', 'Tsai, Wei-Lun', 'Chen, Jih-Jung', 'Kubota, Toru', 'Matsuoka, Mayumi', 'Chen, Siang-Ru', 'Yang, Chih-Shiang', 'Lu, Ruo-Wei', 'Lin, Yi-Ling', 'Chang, Tsung-Hsien']",,,,
,PMC,Bioethics in Practice - A Quarterly Column About Medical Ethics: Ebola and Medical Ethics - Ethical Challenges in the Management of Contagious Infectious Diseases,,PMC4365847,,,,,"['Blais, Christopher M.', 'White, Janet L.']",,,,
,PMC,Microbial Air Quality and Bacterial Surface Contamination in Ambulances During Patient Services,http://dx.doi.org/10.5001/omj.2015.23,PMC4412456,,,"OBJECTIVES: We sought to assess microbial air quality and bacterial surface contamination on medical instruments and the surrounding areas among 30 ambulance runs during service. METHODS: We performed a cross-sectional study of 106 air samples collected from 30 ambulances before patient services and 212 air samples collected during patient services to assess the bacterial and fungal counts at the two time points. Additionally, 226 surface swab samples were collected from medical instrument surfaces and the surrounding areas before and after ambulance runs. Groups or genus of isolated bacteria and fungi were preliminarily identified by Gram’s stain and lactophenol cotton blue. Data were analyzed using descriptive statistics, t-test, and Pearson’s correlation coefficient with a p-value of less than 0.050 considered significant. RESULTS: The mean and standard deviation of bacterial and fungal counts at the start of ambulance runs were 318±485cfu/m(3) and 522±581cfu/m(3), respectively. Bacterial counts during patient services were 468±607cfu/m(3) and fungal counts were 656±612cfu/m(3). Mean bacterial and fungal counts during patient services were significantly higher than those at the start of ambulance runs, p=0.005 and p=0.030, respectively. For surface contamination, the overall bacterial counts before and after patient services were 0.8±0.7cfu/cm(2) and 1.3±1.1cfu/cm(2), respectively (p<0.001). The predominant isolated bacteria and fungi were Staphylococcus spp. and Aspergillus spp., respectively. Additionally, there was a significantly positive correlation between bacterial (r=0.3, p<0.010) and fungal counts (r=0.2, p=0.020) in air samples and bacterial counts on medical instruments and allocated areas. CONCLUSIONS: This study revealed high microbial contamination (bacterial and fungal) in ambulance air during services and higher bacterial contamination on medical instrument surfaces and allocated areas after ambulance services compared to the start of ambulance runs. Additionally, bacterial and fungal counts in ambulance air showed a significantly positive correlation with the bacterial surface contamination on medical instruments and allocated areas. Further studies should be conducted to determine the optimal intervention to reduce microbial contamination in the ambulance environment.",,"['Luksamijarulkul, Pipat', 'Pipitsangjan, Sirikun']",,,,
,PMC,"Law, Medicine, and Public Health Preparedness: The Case of Ebola",,PMC4315863,,,,,"['Hodge, James G.', 'Gostin, Lawrence O.', 'Hanfling, Dan', 'Hick, John L.']",,,,
,PMC,The Structure and Functions of Coronavirus Genomic 3’ and 5’ Ends,http://dx.doi.org/10.1016/j.virusres.2015.02.025,PMC4476908,,,"Coronaviruses (CoVs) are an important cause of illness in humans and animals. Most human coronaviruses commonly cause relatively mild respiratory illnesses; however two zoonotic coronaviruses, SARS-CoV and MERS-CoV, can cause severe illness and death. Investigations over the past thirty-five years have illuminated many aspects of coronavirus replication. The focus of this review is the functional analysis of conserved RNA secondary structures in the 5’ and 3’ of the betacoronavirus genomes. The 5’ 350 nucleotides folds into a set of RNA secondary structures which are well conserved, and reverse genetic studies indicate that these structures play an important role in the discontinuous synthesis of subgenomic RNAs in the betacoronaviruses. These cis-acting elements extend 3’ of the 5’UTR into ORF1a. The 3’UTR is similarly conserved and contains all of the cis-acting sequences necessary for viral replication. Two competing conformations near the 5’ end of the 3’UTR have been shown to make up a potential molecular switch. There is some evidence that an association between the 3’ and 5’UTRs is necessary for subgenomic RNA synthesis, but the basis for this association is not yet clear. A number of host RNA proteins have been shown to bind to the 5’ and 3’ cis-acting regions, but the significance of these in viral replication is not clear. Two viral proteins have been identified as binding to the 5’ cis-acting region, nsp1 and N protein. A genetic interaction between nsp8 and nsp9 and the region of the 3’UTR that contains the putative molecular switch suggests that these two proteins bind to this region.",,"['Yang, Dong', 'Leibowitz, Julian L.']",,,,
,PMC,Effect of Temperature and Relative Humidity on the Survival of Foodborne Viruses during Food Storage,http://dx.doi.org/10.1128/AEM.04093-14,PMC4345369,,,"Millions of people suffer from foodborne diseases throughout the world every year, and the importance of food safety has grown worldwide in recent years. The aim of this study was to investigate the survival of hepatitis A virus (HAV) and viral surrogates of human norovirus (HuNoV) (bacteriophage MS2 and murine norovirus [MNV]) in food over time. HAV, MNV, and MS2 were inoculated onto either the digestive gland of oysters or the surface of fresh peppers, and their survival on these food matrices was measured under various temperature (4°C, 15°C, 25°C, and 40°C) and relative humidity (RH) (50% and 70%) conditions. Inoculated viruses were recovered from food samples and quantified by a plaque assay at predetermined time points over 2 weeks (0, 1, 3, 7, 10, and 14 days). Virus survival was influenced primarily by temperature. On peppers at 40°C and at 50% RH, >4- and 6-log reductions of MNV and HAV, respectively, occurred within 1 day. All three viruses survived better on oysters. In addition, HAV survived better at 70% RH than at 50% RH. The survival data for HAV, MS2, and MNV were fit to three different mathematical models (linear, Weibull, and biphasic models). Among them, the biphasic model was optimum in terms of goodness of fit. The results of this study suggest that major foodborne viruses such as HAV and HuNoV can survive over prolonged periods of time with a limited reduction in numbers. Because a persistence of foodborne virus on contaminated foods was observed, precautionary preventive measures should be performed.",,"['Lee, Su Jin', 'Si, Jiyeon', 'Yun, Hyun Sun', 'Ko, GwangPyo']",,,,
,PMC,An exploration of the properties of the CORE problem list subset and how it facilitates the implementation of SNOMED CT,http://dx.doi.org/10.1093/jamia/ocu022,PMC5566198,,,"Objective Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) is the emergent international health terminology standard for encoding clinical information in electronic health records. The CORE Problem List Subset was created to facilitate the terminology’s implementation. This study evaluates the CORE Subset’s coverage and examines its growth pattern as source datasets are being incorporated. Methods Coverage of frequently used terms and the corresponding usage of the covered terms were assessed by “leave-one-out” analysis of the eight datasets constituting the current CORE Subset. The growth pattern was studied using a retrospective experiment, growing the Subset one dataset at a time and examining the relationship between the size of the starting subset and the coverage of frequently used terms in the incoming dataset. Linear regression was used to model that relationship. Results On average, the CORE Subset covered 80.3% of the frequently used terms of the left-out dataset, and the covered terms accounted for 83.7% of term usage. There was a significant positive correlation between the CORE Subset’s size and the coverage of the frequently used terms in an incoming dataset. This implies that the CORE Subset will grow at a progressively slower pace as it gets bigger. Conclusion The CORE Problem List Subset is a useful resource for the implementation of Systematized Nomenclature of Medicine Clinical Terms in electronic health records. It offers good coverage of frequently used terms, which account for a high proportion of term usage. If future datasets are incorporated into the CORE Subset, it is likely that its size will remain small and manageable.",,"['Fung, Kin Wah', 'Xu, Julia']",,,,
,PMC,Coronavirus Envelope (E) Protein Remains at the Site of Assembly,http://dx.doi.org/10.1016/j.virol.2015.02.005,PMC4550588,,,"Coronaviruses (CoVs) assemble at endoplasmic reticulum Golgi intermediate compartment (ERGIC) membranes and egress from cells in cargo vesicles. Only a few molecules of the envelope (E) protein are assembled into virions. The role of E in morphogenesis is not fully understood. The cellular localization and dynamics of mouse hepatitis CoV A59 (MHV) E protein were investigated to further understanding of its role during infection. E protein localized in the ERGIC and Golgi with the amino and carboxy termini in the lumen and cytoplasm, respectively. E protein does not traffic to the cell surface. MHV was genetically engineered with a tetracysteine tag at the carboxy end of E. Fluorescence recovery after photobleaching (FRAP) showed that E is mobile in ERGIC/Golgi membranes. Correlative light electron microscopy (CLEM) confirmed the presence of E in Golgi cisternae. The results provide strong support that E proteins carry out their function(s) at the site of budding/assembly.",,"['Venkatagopalan, Pavithra', 'Daskalova, Sasha M.', 'Lopez, Lisa A.', 'Dolezal, Kelly A.', 'Hogue, Brenda G.']",,,,
,PMC,2014 MERS-CoV Outbreak in Jeddah — A Link to Health Care Facilities,http://dx.doi.org/10.1056/NEJMoa1408636,PMC5710730,,,"BACKGROUND: A marked increase in the number of cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred in Jeddah, Saudi Arabia, in early 2014. We evaluated patients with MERS-CoV infection in Jeddah to explore reasons for this increase and to assess the epidemiologic and clinical features of this disease. METHODS: We identified all cases of laboratory-confirmed MERS-CoV infection in Jeddah that were reported to the Saudi Arabian Ministry of Health from January 1 through May 16, 2014. We conducted telephone interviews with symptomatic patients who were not health care personnel, and we reviewed hospital records. We identified patients who were reported as being asymptomatic and interviewed them regarding a history of symptoms in the month before testing. Descriptive analyses were performed. RESULTS: Of 255 patients with laboratory-confirmed MERS-CoV infection, 93 died (case fatality rate, 36.5%). The median age of all patients was 45 years (interquartile range, 30 to 59), and 174 patients (68.2%) were male. A total of 64 patients (25.1%) were reported to be asymptomatic. Of the 191 symptomatic patients, 40 (20.9%) were health care personnel. Among the 151 symptomatic patients who were not health care personnel, 112 (74.2%) had data that could be assessed, and 109 (97.3%) of these patients had had contact with a health care facility, a person with a confirmed case of MERS-CoV infection, or someone with severe respiratory illness in the 14 days before the onset of illness. The remaining 3 patients (2.7%) reported no such contacts. Of the 64 patients who had been reported as asymptomatic, 33 (52%) were interviewed, and 26 of these 33 (79%) reported at least one symptom that was consistent with a viral respiratory illness. CONCLUSIONS: The majority of patients in the Jeddah MERS-CoV outbreak had contact with a health care facility, other patients, or both. This highlights the role of health care–associated transmission. (Supported by the Ministry of Health, Saudi Arabia, and by the U.S. Centers for Disease Control and Prevention.)",,"['Oboho, Ikwo K.', 'Tomczyk, Sara M.', 'Al-Asmari, Ahmad M.', 'Banjar, Ayman A.', 'Al-Mugti, Hani', 'Aloraini, Muhannad S.', 'Alkhaldi, Khulud Z.', 'Almohammadi, Emad L.', 'Alraddadi, Basem M.', 'Gerber, Susan I.', 'Swerdlow, David L.', 'Watson, John T.', 'Madani, Tariq A.']",,,,
,PMC,Community-Acquired Pneumonia Requiring Hospitalization among U.S. Children,http://dx.doi.org/10.1056/NEJMoa1405870,PMC4697461,,,"BACKGROUND: U.S. incidence estimates of pediatric community-acquired pneumonia hospitalizations based on prospective data collection are limited. Updated estimates with radiographic confirmation and current laboratory diagnostics are needed. METHODS: We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among children <18 years in three hospitals in Memphis, Nashville, and Salt Lake City. We excluded children with recent hospitalization and severe immunosuppression. Blood and respiratory specimens were systematically collected for pathogen detection by multiple modalities. Chest radiographs were independently reviewed by study radiologists. We calculated population-based incidence rates of community-acquired pneumonia hospitalizations, overall and by age and pathogen. RESULTS: From January 2010-June 2012, we enrolled 2638 (69%) of 3803 eligible children; 2358 (89%) had radiographic pneumonia. Median age was 2 years (interquartile range 1-6); 497 (21%) children required intensive care, and three (<1%) died. Among 2222 children with radiographic pneumonia and specimens available for both bacterial and viral testing, a viral and/or bacterial pathogen was detected in 1802 (81%); ≥1 virus in 1472 (66%), bacteria in 175 (8%), and bacterial-viral co-detection in 155 (7%). Annual pneumonia incidence was 15.7/10,000 children [95% confidence interval (CI) 14.9-16.5], with highest rates among children <2 years [62.2/10,000 (CI 57.6-67.1)]. Respiratory syncytial virus (37% vs. 8%), adenovirus (15% vs. 3%), and human metapneumovirus (15% vs. 8%) were more commonly detected in children <5 years compared with older children; Mycoplasma pneumoniae (19% vs. 3%) was more common in children ≥5 years. CONCLUSIONS: Pediatric community-acquired pneumonia hospitalization burden was highest among the very young, with respiratory viruses most commonly detected.",,"['Jain, Seema', 'Williams, Derek J.', 'Arnold, Sandra R.', 'Ampofo, Krow', 'Bramley, Anna M.', 'Reed, Carrie', 'Stockmann, Chris', 'Anderson, Evan J.', 'Grijalva, Carlos G.', 'Self, Wesley H.', 'Zhu, Yuwei', 'Patel, Anami', 'Hymas, Weston', 'Chappell, James D.', 'Kaufman, Robert A.', 'Kan, J. Herman', 'Dansie, David', 'Lenny, Noel', 'Hillyard, David R.', 'Haynes, Lia M.', 'Levine, Min', 'Lindstrom, Stephen', 'Winchell, Jonas M.', 'Katz, Jacqueline M.', 'Erdman, Dean', 'Schneider, Eileen', 'Hicks, Lauri A.', 'Wunderink, Richard G.', 'Edwards, Kathryn M.', 'Pavia, Andrew T.', 'McCullers, Jonathan A.', 'Finelli, Lyn', None]",,,,
,PMC,"Public risk perception and attitudes towards live poultry markets before and after their closure due to influenza A(H7N9), Hong Kong, January–February 2014",http://dx.doi.org/10.1093/pubmed/fdv020,PMC4750522,,,"BACKGROUND: The study investigated public risk perception regarding influenza A(H7N9) and attitudes towards closure of live poultry markets (LPMs) before and after LPMs closed in Hong Kong. METHODS: Two population-based surveys were conducted before and after LPMs closed in January–February 2014, respectively. Adults were recruited using random digital dialing. RESULTS: In total, 670 and 1011 respondents completed the survey before and after closure of LPMs, respectively. Perceived susceptibility to H7N9 infection was low across surveys. Among respondents who completed the survey after LPMs closed, only 14.6% agreed that temporary closure of LPMs caused inconvenience to the daily life; 38.7% valued the Chinese tradition of live poultry consumption more than controlling the risk of avian influenza; 54.6% recognized greater risk of influenza epidemic associated with LPMs. Support for permanent closure of LPMs which was comparably low across surveys was strongly associated with perceived risk of avian influenza related to LPMs, the effectiveness of LPM closure in control of avian influenza and the inconvenience caused by closure. CONCLUSIONS: Risk communication that promotes people's perceived risk of avian influenza associated with LPMs and the effectiveness of LPM closure in control of avian influenza outbreaks may improve support for permanent closure of LPMs.",,"['Liao, Qiuyan', 'Wu, Peng', 'Lam, Wendy Wing Tak', 'Fang, Vicky J.', 'Wu, Joseph T.', 'Leung, Gabriel M.', 'Fielding, Richard', 'Cowling, Benjamin J.']",,,,
,PMC,"Oropouche Virus Infection and Pathogenesis Are Restricted by MAVS, IRF-3, IRF-7, and Type I Interferon Signaling Pathways in Nonmyeloid Cells",http://dx.doi.org/10.1128/JVI.00077-15,PMC4403474,,,"Oropouche virus (OROV) is a member of the Orthobunyavirus genus in the Bunyaviridae family and a prominent cause of insect-transmitted viral disease in Central and South America. Despite its clinical relevance, little is known about OROV pathogenesis. To define the host defense pathways that control OROV infection and disease, we evaluated OROV pathogenesis and immune responses in primary cells and mice that were deficient in the RIG-I-like receptor signaling pathway (MDA5, RIG-I, or MAVS), downstream regulatory transcription factors (IRF-3 or IRF-7), beta interferon (IFN-β), or the receptor for type I IFN signaling (IFNAR). OROV replicated to higher levels in primary fibroblasts and dendritic cells lacking MAVS signaling, the transcription factors IRF-3 and IRF-7, or IFNAR than in wild-type (WT) cells. In mice, deletion of IFNAR, MAVS, or IRF-3 and IRF-7 resulted in uncontrolled OROV replication, hypercytokinemia, extensive liver damage, and death, whereas WT congenic animals failed to develop disease. Unexpectedly, mice with a selective deletion of IFNAR on myeloid cells (CD11c Cre(+) Ifnar(f/f) or LysM Cre(+) Ifnar(f/f)) did not sustain enhanced disease with OROV or a selective (flox/flox) deletion La Crosse virus, a closely related encephalitic orthobunyavirus. In bone marrow chimera studies, recipient irradiated Ifnar(−/−) mice reconstituted with WT hematopoietic cells sustained high levels of OROV replication and liver damage, whereas WT mice reconstituted with Ifnar(−/−) bone marrow were resistant to disease. Collectively, these results establish a dominant protective role for MAVS, IRF-3 and IRF-7, and IFNAR in restricting OROV infection and tissue injury and suggest that IFN signaling in nonmyeloid cells contributes to the host defense against orthobunyaviruses. IMPORTANCE Oropouche virus (OROV) is an emerging arthropod-transmitted orthobunyavirus that causes episodic outbreaks of a debilitating febrile illness in humans in countries of South and Central America. The continued expansion of the range and number of its arthropod vectors increases the likelihood that OROV will spread into new regions. At present, the pathogenesis of OROV in humans or other vertebrate animals remains poorly understood. To define cellular mechanisms of control of OROV infection, we performed infection studies in a series of primary cells and mice that were deficient in key innate immune genes involved in pathogen recognition and control. Our results establish that a MAVS-dependent type I IFN signaling pathway has a dominant role in restricting OROV infection and pathogenesis in vivo.",,"['Proenca-Modena, Jose Luiz', 'Sesti-Costa, Renata', 'Pinto, Amelia K.', 'Richner, Justin M.', 'Lazear, Helen M.', 'Lucas, Tiffany', 'Hyde, Jennifer L.', 'Diamond, Michael S.']",,,,
,PMC,Intracisternal Cyclodextrin Prevents Cerebellar Dysfunction and Purkinje Cell Death in Feline Niemann-Pick type C1 disease,http://dx.doi.org/10.1126/scitranslmed.3010101,PMC4415615,,,"Niemann-Pick type C1 (NPC) disease is a lysosomal storage disease caused by mutations in the NPC1 gene, leading to an increase in unesterified cholesterol and several sphingolipids, and resulting in hepatic disease and progressive neurological disease. Whereas subcutaneous administration of the pharmaceutical excipient 2-hydroxypropyl-beta-cyclodextrin (HPβCD) ameliorated hepatic disease, doses sufficient to reduce neurological disease resulted in pulmonary toxicity. In contrast, direct administration of HPβCD into the cisterna magna of presymptomatic cats with NPC disease prevented the onset of cerebellar dysfunction for greater than a year and resulted in a reduction in Purkinje cell loss and near normal concentrations of cholesterol and sphingolipids. Moreover, administration of intracisternal HPβCD to NPC cats with ongoing cerebellar dysfunction slowed disease progression, increased survival time, and decreased the accumulation of brain gangliosides. An increase in hearing threshold was identified as a potential adverse effect. Together, these studies in the feline animal model have provided critical data on efficacy and safety of drug administration directly into the CNS that will be important for advancing HPβCD into clinical trials.",,"['Vite, C. H.', 'Bagel, J. H.', 'Swain, G. P.', 'Prociuk, M.', 'Sikora, T. U.', 'Stein, V. M.', 'O’Donnell, P.', 'Ruane, T.', 'Ward, S.', 'Crooks, A.', 'Li, S.', 'Mauldin, E.', 'Stellar, S.', 'De Meulder, M.', 'Kao, M. L.', 'Ory, D. S.', 'Davidson, C.', 'Vanier, M. T.', 'Walkley, S. U.']",,,,
,PMC,Silencing the alarms: innate immune antagonism by rotavirus NSP1 and VP3,http://dx.doi.org/10.1016/j.virol.2015.01.006,PMC4940189,,,"The innate immune response involves a broad array of pathogen sensors that stimulate the production of interferons (IFN) to induce an antiviral state. Rotavirus, a significant cause of childhood gastroenteritis and a member of the Reoviridae family of segmented, double-stranded RNA viruses, encodes at least two direct antagonists of host innate immunity: NSP1 and VP3. NSP1, a putative E3 ubiquitin ligase, mediates the degradation of cellular factors involved in both IFN induction and downstream signaling. VP3, the viral capping enzyme, utilizes a 2H-phosphodiesterase domain to prevent activation of the cellular oligoadenylate synthase (OAS)-RNase L pathway. Computational, molecular, and biochemical studies have provided key insights into the structural and mechanistic basis of innate immune antagonism by NSP1 and VP3 of group A rotaviruses (RVA). Future studies with non-RVA isolates will be essential to understand how other RV species evade host innate immune responses.",,"['Morelli, Marco', 'Ogden, Kristen M.', 'Patton, John T.']",,,,
,PMC,Emerging roles for RNA degradation in viral replication and antiviral defense,http://dx.doi.org/10.1016/j.virol.2015.02.007,PMC4424162,,,"Viral replication significantly alters the gene expression landscape of infected cells. Many of these changes are driven by viral manipulation of host transcription or translation machinery. Several mammalian viruses encode factors that broadly dampen gene expression by directly targeting messenger RNA (mRNA). Here, we highlight how these factors promote mRNA degradation to globally regulate both host and viral gene expression. Although these viral factors are not homologous and use distinct mechanisms to target mRNA, many of them display striking parallels in their strategies for executing RNA degradation and invoke key features of cellular RNA quality control pathways. In some cases, there is a lack of selectivity for degradation of host versus viral mRNA, indicating that the purposes of virus-induced mRNA degradation extend beyond redirecting cellular resources towards viral gene expression. In addition, several antiviral pathways use RNA degradation as a viral restriction mechanism, and we will summarize new findings related to how these host-encoded ribonucleases target and destroy viral RNA.",,"['Abernathy, Emma', 'Glaunsinger, Britt']",,,,
,PMC,Does the Necrosis Develop Simultaneously in Patients with Bilateral Hips Necrosis? A Case Report,http://dx.doi.org/10.1111/os.12162,PMC6583555,,,,,"['Zhao, Feng‐chao', 'Cang, Ding‐wei', 'Shen, Xiao‐fei', 'Guo, Kai‐jin']",,,,
,PMC,Mechanisms of mRNA frame maintenance and its subversion during translation of the genetic code,http://dx.doi.org/10.1016/j.biochi.2015.02.007,PMC4458409,,,"Important viral and cellular gene products are regulated by stop codon readthrough and mRNA frameshifting, processes whereby the ribosome detours from the reading frame defined by three nucleotide codons after initiation of translation. In the last few years, rapid progress has been made in mechanistically characterizing both processes and also revealing that trans-acting factors play important regulatory roles in frameshifting. Here, we review recent biophysical studies that bring new molecular insights to stop codon readthrough and frameshifting. Lastly, we consider whether there may be common mechanistic themes in −1 and +1 frameshifting based on recent X-ray crystal structures of +1 frameshift-prone tRNAs bound to the ribosome.",,"['Dunkle, Jack A.', 'Dunham, Christine M.']",,,,
,PMC,Middle East Respiratory Syndrome Coronavirus: Update for Clinicians,http://dx.doi.org/10.1093/cid/civ118,PMC5730266,,,"Although much recent focus has been on the recognition of Ebola virus disease among travelers from West Africa, cases of Middle East respiratory syndrome coronavirus (MERS-CoV), including travel-associated cases, continue to be reported. US clinicians need to be familiar with recommendations regarding when to suspect MERS-CoV, how to make a diagnosis, and what infection control measures need to be instituted when a case is suspected. Infection control is especially critical, given that most cases have been healthcare-associated. Two cases of MERS-CoV were identified in the United States in May 2014; because these cases were detected promptly and appropriate control measures were put in place quickly, no secondary cases occurred. This paper summarizes information that US clinicians need to know to prevent secondary cases of MERS-CoV from occurring in the United States.",,"['Rasmussen, Sonja A.', 'Gerber, Susan I.', 'Swerdlow, David L.']",,,,
,PMC,Multiple drug resistant organisms in healthcare: the failure of contact precautions,http://dx.doi.org/10.1177/1757177415570104,PMC5074191,,,,,"['Simmons, Bryan P', 'Larson, Elaine L']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00161-15,PMC4337526,,,,,,,,,
,PMC,Early Detection of Dengue Virus by Use of Reverse Transcription-Recombinase Polymerase Amplification,http://dx.doi.org/10.1128/JCM.02648-14,PMC4390637,,,"A method for the rapid diagnosis of early dengue virus (DENV) infection is highly needed. Here, a prototype reverse transcription-recombinase polymerase amplification (RT-RPA) assay was developed. The assay detected DENV RNA in <20 min without the need for thermocycling amplification. The assay enabled the detection of as few as 10 copies of DENV RNA. The designed RT-RPA primers and exo probe detected the DENV genome of at least 12 genotypes of DENV circulating globally without cross-reacting with other arboviruses. We assessed the diagnostic performance of the RT-RPA assay for the detection of DENV RNA in 203 serum samples of patients with clinically suspected dengue. The sera were simultaneously tested for DENV using a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay, quantitative RT-PCR (qRT-PCR), and IgM- and IgG-capture enzyme-linked immunosorbent assays (ELISA). Acute DENV infection was confirmed in 130 samples and 61 of the samples (46.9%) were classified as viremic with qRT-PCR. The RT-RPA assay showed good concordance (κ of ≥0.723) with the RT-LAMP and qRT-PCR assays in detecting the dengue viremic samples. When used in combination with ELISA, both the RT-RPA and RT-LAMP assays increased the detection of acute DENV infection to ≥95.7% (≥45/47) in samples obtained within 5 days of illness. The results from the study suggest that the RT-RPA assay is the most rapid molecular diagnostic tool available for the detection of DENV. Hence, it is possible to use the RT-RPA assay in a laboratory to complement routine serology testing for dengue.",,"['Teoh, Boon-Teong', 'Sam, Sing-Sin', 'Tan, Kim-Kee', 'Danlami, Mohammed Bashar', 'Shu, Meng-Hooi', 'Johari, Jefree', 'Hooi, Poh-Sim', 'Brooks, David', 'Piepenburg, Olaf', 'Nentwich, Oliver', 'Wilder-Smith, Annelies', 'Franco, Leticia', 'Tenorio, Antonio', 'AbuBakar, Sazaly']",,,,
,PMC,Less Is More: An Adaptive Branch-Site Random Effects Model for Efficient Detection of Episodic Diversifying Selection,http://dx.doi.org/10.1093/molbev/msv022,PMC4408413,,,"Over the past two decades, comparative sequence analysis using codon-substitution models has been honed into a powerful and popular approach for detecting signatures of natural selection from molecular data. A substantial body of work has focused on developing a class of “branch-site” models which permit selective pressures on sequences, quantified by the ω ratio, to vary among both codon sites and individual branches in the phylogeny. We develop and present a method in this class, adaptive branch-site random effects likelihood (aBSREL), whose key innovation is variable parametric complexity chosen with an information theoretic criterion. By applying models of different complexity to different branches in the phylogeny, aBSREL delivers statistical performance matching or exceeding best-in-class existing approaches, while running an order of magnitude faster. Based on simulated data analysis, we offer guidelines for what extent and strength of diversifying positive selection can be detected reliably and suggest that there is a natural limit on the optimal parametric complexity for “branch-site” models. An aBSREL analysis of 8,893 Euteleostomes gene alignments demonstrates that over 80% of branches in typical gene phylogenies can be adequately modeled with a single ω ratio model, that is, current models are unnecessarily complicated. However, there are a relatively small number of key branches, whose identities are derived from the data using a model selection procedure, for which it is essential to accurately model evolutionary complexity.",,"['Smith, Martin D.', 'Wertheim, Joel O.', 'Weaver, Steven', 'Murrell, Ben', 'Scheffler, Konrad', 'Kosakovsky Pond, Sergei L.']",,,,
,PMC,Murine Coronavirus Ubiquitin-Like Domain Is Important for Papain-Like Protease Stability and Viral Pathogenesis,http://dx.doi.org/10.1128/JVI.00338-15,PMC4403493,,,"Ubiquitin-like domains (Ubls) now are recognized as common elements adjacent to viral and cellular proteases; however, their function is unclear. Structural studies of the papain-like protease (PLP) domains of coronaviruses (CoVs) revealed an adjacent Ubl domain in severe acute respiratory syndrome CoV, Middle East respiratory syndrome CoV, and the murine CoV, mouse hepatitis virus (MHV). Here, we tested the effect of altering the Ubl adjacent to PLP2 of MHV on enzyme activity, viral replication, and pathogenesis. Using deletion and substitution approaches, we identified sites within the Ubl domain, residues 785 to 787 of nonstructural protein 3, which negatively affect protease activity, and valine residues 785 and 787, which negatively affect deubiquitinating activity. Using reverse genetics, we engineered Ubl mutant viruses and found that AM2 (V787S) and AM3 (V785S) viruses replicate efficiently at 37°C but generate smaller plaques than wild-type (WT) virus, and AM2 is defective for replication at higher temperatures. To evaluate the effect of the mutation on protease activity, we purified WT and Ubl mutant PLP2 and found that the proteases exhibit similar specific activities at 25°C. However, the thermal stability of the Ubl mutant PLP2 was significantly reduced at 30°C, thereby reducing the total enzymatic activity. To determine if the destabilizing mutation affects viral pathogenesis, we infected C57BL/6 mice with WT or AM2 virus and found that the mutant virus is highly attenuated, yet it replicates sufficiently to elicit protective immunity. These studies revealed that modulating the Ubl domain adjacent to the PLP reduces protease stability and viral pathogenesis, revealing a novel approach to coronavirus attenuation. IMPORTANCE Introducing mutations into a protein or virus can have either direct or indirect effects on function. We asked if changes in the Ubl domain, a conserved domain adjacent to the coronavirus papain-like protease, altered the viral protease activity or affected viral replication or pathogenesis. Our studies using purified wild-type and Ubl mutant proteases revealed that mutations in the viral Ubl domain destabilize and inactivate the adjacent viral protease. Furthermore, we show that a CoV encoding the mutant Ubl domain is unable to replicate at high temperature or cause lethal disease in mice. Our results identify the coronavirus Ubl domain as a novel modulator of viral protease stability and reveal manipulating the Ubl domain as a new approach for attenuating coronavirus replication and pathogenesis.",,"['Mielech, Anna M.', 'Deng, Xufang', 'Chen, Yafang', 'Kindler, Eveline', 'Wheeler, Dorthea L.', 'Mesecar, Andrew D.', 'Thiel, Volker', 'Perlman, Stanley', 'Baker, Susan C.']",,,,
,PMC,Broad-Spectrum Inhibitors against 3C-Like Proteases of Feline Coronaviruses and Feline Caliciviruses,http://dx.doi.org/10.1128/JVI.03688-14,PMC4403489,,,"Feline infectious peritonitis and virulent, systemic calicivirus infection are caused by certain types of feline coronaviruses (FCoVs) and feline caliciviruses (FCVs), respectively, and are important infectious diseases with high fatality rates in members of the Felidae family. While FCoV and FCV belong to two distinct virus families, the Coronaviridae and the Caliciviridae, respectively, they share a dependence on viral 3C-like protease (3CLpro) for their replication. Since 3CLpro is functionally and structurally conserved among these viruses and essential for viral replication, 3CLpro is considered a potential target for the design of antiviral drugs with broad-spectrum activities against these distinct and highly important viral infections. However, small-molecule inhibitors against the 3CLpro enzymes of FCoV and FCV have not been previously identified. In this study, derivatives of peptidyl compounds targeting 3CLpro were synthesized and evaluated for their activities against FCoV and FCV. The structures of compounds that showed potent dual antiviral activities with a wide margin of safety were identified and are discussed. Furthermore, the in vivo efficacy of 3CLpro inhibitors was evaluated using a mouse model of coronavirus infection. Intraperitoneal administration of two 3CLpro inhibitors in mice infected with murine hepatitis virus A59, a hepatotropic coronavirus, resulted in significant reductions in virus titers and pathological lesions in the liver compared to the findings for the controls. These results suggest that the series of 3CLpro inhibitors described here may have the potential to be further developed as therapeutic agents against these important viruses in domestic and wild cats. This study provides important insights into the structure and function relationships of 3CLpro for the design of antiviral drugs with broader antiviral activities. IMPORTANCE Feline infectious peritonitis virus (FIPV) is the leading cause of death in young cats, and virulent, systemic feline calicivirus (vs-FCV) causes a highly fatal disease in cats for which no preventive or therapeutic measure is available. The genomes of these distinct viruses, which belong to different virus families, encode a structurally and functionally conserved 3C-like protease (3CLpro) which is a potential target for broad-spectrum antiviral drug development. However, no studies have previously reported a structural platform for the design of antiviral drugs with activities against these viruses or on the efficacy of 3CLpro inhibitors against coronavirus infection in experimental animals. In this study, we explored the structure-activity relationships of the derivatives of 3CLpro inhibitors and identified inhibitors with potent dual activities against these viruses. In addition, the efficacy of the 3CLpro inhibitors was demonstrated in mice infected with a murine coronavirus. Overall, our study provides the first insight into a structural platform for anti-FIPV and anti-FCV drug development.",,"['Kim, Yunjeong', 'Shivanna, Vinay', 'Narayanan, Sanjeev', 'Prior, Allan M.', 'Weerasekara, Sahani', 'Hua, Duy H.', 'Kankanamalage, Anushka C. Galasiti', 'Groutas, William C.', 'Chang, Kyeong-Ok']",,,,
,PMC,The Laminin Receptor Is a Cellular Attachment Receptor for Classical Swine Fever Virus,http://dx.doi.org/10.1128/JVI.00019-15,PMC4403484,,,"Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious, economically important viral disease in many countries. The E(rns) and E2 envelope glycoproteins are responsible for the binding to and entry into the host cell by CSFV. To date, only one cellular receptor, heparan sulfate (HS), has been identified as being involved in CSFV attachment. HS is also present on the surface of various cells that are nonpermissive to CSFV. Hence, there must be another receptor(s) that has been unidentified to date. In this study, we used a set of small interfering RNAs (siRNAs) against a number of porcine cell membrane protein genes to screen cellular proteins involved in CSFV infection. This approach resulted in the identification of several proteins, and of these, the laminin receptor (LamR) has been demonstrated to be a cellular receptor for several viruses. Confocal analysis showed that LamR is colocalized with CSFV virions on the membrane, and a coimmunoprecipitation assay indicated that LamR interacts with the CSFV E(rns) protein. In inhibition assays, anti-LamR antibodies, soluble laminin, or LamR protein significantly inhibited CSFV infection in a dose-dependent manner. Transduction of PK-15 cells with a recombinant lentivirus expressing LamR yielded higher viral titers. Moreover, an attachment assay demonstrated that LamR functions during virus attachment. We also demonstrate that LamR acts as an alternative attachment receptor, especially in SK6 cells. These results indicate that LamR is a cellular attachment receptor for CSFV. IMPORTANCE Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), an economically important viral disease affecting the pig industry in many countries. To date, only heparan sulfate (HS) has been identified to be an attachment receptor for CSFV. Here, using RNA interference screening with small interfering RNAs (siRNAs) against a number of porcine membrane protein genes, we identified the laminin receptor (LamR) to be another attachment receptor. We demonstrate the involvement of LamR together with HS in virus attachment, and we elucidate the relationship between LamR and HS. LamR also serves as an attachment receptor for many viral pathogens, including dengue virus, a fatal human flavivirus. The study will help to enhance our understanding of the life cycle of flaviviruses and the development of antiviral strategies for flaviviruses.",,"['Chen, Jianing', 'He, Wen-Rui', 'Shen, Liang', 'Dong, Hong', 'Yu, Jiahui', 'Wang, Xiao', 'Yu, Shaoxiong', 'Li, Yongfeng', 'Li, Su', 'Luo, Yuzi', 'Sun, Yuan', 'Qiu, Hua-Ji']",,,,
,PMC,Unsanctioned travel restrictions related to Ebola unravel the global social contract,http://dx.doi.org/10.1503/cmaj.141488,PMC4330134,,,,,"Pattani, Reena",,,,
,PMC,MKK3 mediates inflammatory response through modulation of mitochondrial function,http://dx.doi.org/10.1016/j.freeradbiomed.2015.01.035,PMC4441852,,,"Mitochondria are increasingly recognized as drivers of inflammatory responses. MAP kinase kinase 3 (MKK3), a dual-specificity protein kinase, is activated in inflammation and in turn activates p38 MAP kinase signaling. Here we show that MKK3 influences mitochondrial function and acts as a critical mediator of inflammation. MKK3 deficient (MKK3(−/−)) mice and bone marrow derived macrophages (BMDMs) secreted less cytokines than wild type (WT) after LPS exposure. There was improved mitochondrial function, as measured by basal oxygen consumption rate, mitochondrial membrane potential, and ATP production, in MKK3(−/−) BMDMs. After LPS exposure, MKK3(−/−) BMDM did not show significant increase in cellular reactive oxygen species (ROS) production as well as mitochondrial superoxide (MitoSOX) compared to WT. Activation of two important inflammatory mediators i.e. the nuclear translocation of NF-κB and caspase-1 activity (a key component of the inflammasome), were lower in MKK3(−/−) BMDMs. p-38 and JNK activation were lower in MKK3(−/−) BMDMs compared to WT after exposure to LPS. Knockdown of MKK3 by siRNA in wild type BMDMs improved mitochondrial membrane potential, reduced LPS induced caspase-1 activation and attenuated cytokine secretion. Our studies establish MKK3 as a regulator of mitochondrial function and inflammatory responses to LPS and suggest that MKK3 may be a therapeutic target in inflammatory disorders like sepsis.",,"['Srivastava, Anup', 'Shinn, Amanda S.', 'Lee, Patty J.', 'Mannam, Praveen']",,,,
,PMC,Lemmingaid: Happy New Year …,http://dx.doi.org/10.1177/1751143714564509,PMC5593298,,,,,"['Wood,', 'Trees,']",,,,
,PMC,"Ebola: history, treatment, and lessons from a new emerging pathogen",http://dx.doi.org/10.1152/ajplung.00354.2014,PMC4329468,,,,,"Harrod, Kevin S.",,,,
,PMC,Diversification of importin-α isoforms in cellular trafficking and disease states,http://dx.doi.org/10.1042/BJ20141186,PMC4405237,,,"The human genome encodes seven isoforms of importin α which are grouped into three subfamilies known as α1, α2 and α3. All isoforms share a fundamentally conserved architecture that consists of an N-terminal, autoinhibitory, importin-β-binding (IBB) domain and a C-terminal Arm (Armadillo)-core that associates with nuclear localization signal (NLS) cargoes. Despite striking similarity in amino acid sequence and 3D structure, importin-α isoforms display remarkable substrate specificity in vivo. In the present review, we look at key differences among importin-α isoforms and provide a comprehensive inventory of known viral and cellular cargoes that have been shown to associate preferentially with specific isoforms. We illustrate how the diversification of the adaptor importin α into seven isoforms expands the dynamic range and regulatory control of nucleocytoplasmic transport, offering unexpected opportunities for pharmacological intervention. The emerging view of importin α is that of a key signalling molecule, with isoforms that confer preferential nuclear entry and spatiotemporal specificity on viral and cellular cargoes directly linked to human diseases.",,"['Pumroy, Ruth A.', 'Cingolani, Gino']",,,,
,PMC,Clinicopathologic Implications of Eukaryotic Initiation Factor 3f and Her‐2/neu Expression in Gastric Cancer,http://dx.doi.org/10.1111/cts.12263,PMC5351038,,,"BACKGROUND: To detect the expression of eIF3f and human epidermal growth factor receptor 2 (Her‐2)/neu in gastric cancer (GC), correlation with their clinicopathological parameters and the relationship of eIF3f and Her‐2/neu in the occurrence and development of GC. METHODS: A total of 195 gastrectomy specimens with stage I to III were examined for eIF3f expression by immunohistochemistry and for Her‐2/neu expression by fluorescence in situ hybridization (FISH) with the median follow‐up period of 38 months. RESULTS: The positive expression rate of eIF3f in GC and adjacent noncancerous tissue were 33.8% and 59.5%, respectively. eIF3f levels were linked to more advanced tumor stages and likelihood of recurrence (all p < 0.05). The Kaplan–Meier survival curves indicated that decreased expression of eIF3f could serve as a prognosis marker for poor outcome of GC patients (p = 0.04). 15.9% of GC specimens were positive for Her‐2/neu, but whose expression was of no correlation with patients’ survival. Patients who were positive for Her‐2/neu also had high eIF3f expression levels (p = 0.0295). CONCLUSION: Results suggest that eIF3f may play an important role in recurrence, thus representing a promising predictive marker for the prognosis of GC. But Her‐2/neu has no relationship with the prognosis of GC. The clinical significance of eIF3f and Her‐2/neu remains to be further investigated.",,"['Cheng, Yu', 'Zhou, Jin', 'Li, Honglun']",,,,
,PMC,Nonlytic spread of naked viruses,http://dx.doi.org/10.4161/15548627.2014.994372,PMC4502673,,,"How do viruses spread from cell to cell? Enveloped viruses acquire their surrounding membranes by budding: either through the plasma membrane or an internal membrane of infected cells. Thus, a newly budded enveloped virus finds itself either in the extracellular milieu or in a lumenal compartment from which it can exit the cell by conventional secretion. On the other hand, naked viruses such as poliovirus, nodavirus, adenovirus, and SV40 lack an external membrane. They are simply protein-nucleic acid complexes within the cytoplasm or nucleus of the infected cell, and thus would seem to have no other exit route than cell lysis. We have presented the first documentation of nonlytic spread of a naked virus, and showed the interconnections between this event and the process or components of the autophagy pathway.",,"['Bird, Sara W', 'Kirkegaard, Karla']",,,,
,PMC,Transcriptional profile in afferent lymph cells following vaccination with liposomes incorporating CpG,http://dx.doi.org/10.1111/imm.12401,PMC4557688,,,"Vaccine formulations incorporating innate immune stimulants are highly immunogenic; however, the biological signals that originate in the peripheral tissues at the site of injection and are transmitted to the local lymph node to induce immunity remain unclear. By directly cannulating the ovine afferent lymphatic vessels, we have previously shown that it takes 72 hr for mature antigen-loaded dendritic cells and monocytes to appear within afferent lymph following injection of a liposomal formulation containing the Toll-like receptor ligand CpG. In this present study, we characterize the global transcriptional signatures at this time-point in ovine afferent lymph cells as they migrate from the injection site into the lymphatics following vaccination with a liposome antigen formulation incorporating CpG. We show that at 72 hr post vaccination, liposomes alone induce no changes in gene expression and inflammatory profiles within afferent lymph; however, the incorporation of CpG drives interferon, antiviral and cytotoxic gene programmes. This study also measures the expression of key genes within individual cell types in afferent lymph. Antiviral gene signatures are most prominent in lymphocytes, which may play a significant and unexpected role in sustaining the immune response to vaccination at the site of injection. These findings provide a comprehensive analysis of the in vivo immunological pathways that connect the injection site with the local draining lymph node following vaccination.",,"['Neeland, Melanie R', 'Elhay, Martin J', 'Powell, David R', 'Rossello, Fernando J', 'Meeusen, Els N T', 'de Veer, Michael J']",,,,
,PMC,Distinct CD4 T-cell effects on primary versus recall CD8 T-cell responses during viral encephalomyelitis,http://dx.doi.org/10.1111/imm.12378,PMC4557674,,,"CD4 T-cell help is not a universal requirement for effective primary CD8 T cells but is essential to generate memory CD8 T cells capable of recall responses. This study examined how CD4 T cells affect primary and secondary anti-viral CD8 T-cell responses within the central nervous system (CNS) during encephalomyelitis induced by sublethal gliatropic coronavirus. CD4 T-cell depletion before infection did not impair peripheral expansion, interferon-γ production, CNS recruitment or initial CNS effector capacity of virus-specific CD8 T cells ex vivo. Nevertheless, impaired virus control in the absence of CD4 T cells was associated with gradually diminished CNS CD8 T-cell interferon-γ production. Furthermore, within the CD8 T-cell population short-lived effector cells were increased and memory precursor effector cells were significantly decreased, consistent with higher T-cell turnover. Transfer of memory CD8 T cells to reduce viral load in CD4-depleted mice reverted the recipient CNS CD8 T-cell phenotype to that in wild-type control mice. However, memory CD8 T cells primed without CD4 T cells and transferred into infected CD4-sufficient recipients expanded less efficiently and were not sustained in the CNS, contrasting with their helped counterparts. These data suggest that CD4 T cells are dispensable for initial expansion, CNS recruitment and differentiation of primary resident memory CD8 T cells as long as the duration of antigen exposure is limited. By contrast, CD4 T cells are essential to prolong primary CD8 T-cell function in the CNS and imprint memory CD8 T cells for recall responses.",,"['Hwang, Mihyun', 'Phares, Timothy W', 'Hinton, David R', 'Stohlman, Stephen A', 'Bergmann, Cornelia C', 'Min, Booki']",,,,
,PMC,Protection against Klebsiella pneumoniae Using Lithium Chloride in an Intragastric Infection Model,http://dx.doi.org/10.1128/AAC.04261-14,PMC4325792,,,"Intragastric Klebsiella pneumoniae infections of mice can cause liver abscesses, necrosis of liver tissues, and bacteremia. Lithium chloride, a widely prescribed drug for bipolar mood disorder, has been reported to possess anti-inflammatory properties. Using an intragastric infection model, the effects of LiCl on K. pneumoniae infections were examined. Providing mice with drinking water containing LiCl immediately after infection protected them from K. pneumoniae-induced death and liver injuries, such as necrosis of liver tissues, as well as increasing blood levels of aspartate aminotransferase and alanine aminotransferase, in a dose-dependent manner. LiCl administered as late as 24 h postinfection still provided protection. Monitoring of the LiCl concentrations in the sera of K. pneumoniae-infected mice showed that approximately 0.33 mM LiCl was the most effective dose for protecting mice against infections, which is lower than the clinically toxic dose of LiCl. Surveys of bacterial counts and cytokine expression levels in LiCl-treated mice revealed that both were effectively inhibited in blood and liver tissues. Using in vitro assays, we found that LiCl (5 μM to 1 mM) did not directly interfere with the growth of K. pneumoniae but made K. pneumoniae cells lose the mucoid phenotype and become more susceptible to macrophage killing. Furthermore, low doses of LiCl also partially enhanced the bactericidal activity of macrophages. Taken together, these data suggest that LiCl is an alternative therapeutic agent for K. pneumoniae-induced liver infections.",,"['Tsao, Nina', 'Kuo, Chih-Feng', 'Chiu, Ching-Chen', 'Lin, Wei-Chen', 'Huang, Wan-Hui', 'Chen, Li-Yang']",,,,
,PMC,"A Novel Rhabdovirus Isolated from the Straw-Colored Fruit Bat Eidolon helvum, with Signs of Antibodies in Swine and Humans",http://dx.doi.org/10.1128/JVI.02932-14,PMC4442353,,,"Bats have been implicated as reservoirs of emerging viruses. Bat species forming large social groups and roosting in proximity to human communities are of particular interest. In this study, we sampled a colony of ca. 350,000 individuals of the straw-colored fruit bat Eidolon helvum in Kumasi, the second largest city of Ghana. A novel rhabdovirus (Kumasi rhabdovirus [KRV]) was isolated in E. helvum cell cultures and passaged to Vero cells as well as interferon-competent human and primate cells (A549 and MA104). Genome composition was typical for a rhabdovirus. KRV was detected in 5.1% of 487 animals, showing association with the spleen but not the brain. Antibody prevalence was 11.5% by immunofluorescence and 6.4% by plaque reduction virus neutralization test (PRNT). Detection throughout 3 sampling years was pronounced in both annual wet seasons, of which only one overlaps the postparturition season. Juvenile bats showed increased viral prevalence. No evidence of infection was obtained in 1,240 female mosquitos (6 different genera) trapped in proximity to the colony to investigate potential vector association. Antibodies were found in 28.9% (5.4% by PRNT) of 107 swine sera but not in similarly large collections of sheep, goat, or cattle sera. The antibody detection rate in human subjects with occupational exposure to the bat colony was 11% (5/45 persons), which was significantly higher than in unexposed adults (0.8% [1/118]; chi square, P < 0.001). KRV is a novel bat-associated rhabdovirus potentially transmitted to humans and swine. Disease associations should be investigated. IMPORTANCE Bats are thought to carry a huge number of as-yet-undiscovered viruses that may pose epidemic threats to humans and livestock. Here we describe a novel dimarhabdovirus which we isolated from a large colony of the straw-colored fruit bat Eidolon helvum in Ghana. As these animals are exposed to humans and several livestock species, we looked for antibodies indicating infection in humans, cattle, swine, sheep, and goats. Signs of infection were found in swine and humans, with increased antibody findings in humans who are occupationally exposed to the bat colony. Our data suggest that it is worthwhile to look for diseases caused by the novel virus in humans and livestock.",,"['Binger, Tabea', 'Annan, Augustina', 'Drexler, Jan Felix', 'Müller, Marcel Alexander', 'Kallies, René', 'Adankwah, Ernest', 'Wollny, Robert', 'Kopp, Anne', 'Heidemann, Hanna', 'Dei, Dickson', 'Agya-Yao, Festus Courage', 'Junglen, Sandra', 'Feldt, Torsten', 'Kurth, Andreas', 'Oppong, Samuel', 'Adu-Sarkodie, Yaw', 'Drosten, Christian']",,,,
,PMC,Prospective comparison of RT-PCR/ESI-MS to Prodesse ProFlu Plus and Cepheid GenXpert for the detection of Influenza A and B viruses,http://dx.doi.org/10.1016/j.jviromet.2015.01.002,PMC4560249,,,"RT-PCR/ESI-MS has previously demonstrated the capability to detect and identify respiratory viral pathogens in nasopharyngeal swabs. This study expands on previous research by performing a prospective evaluation of RT-PCR/ESI-MS to detect and identify Influenza A and B viruses compared to Prodesse ProFlu Plus and combined ProFlu Plus and Cepheid Xpert Flu. ProFlu Plus was also used as a gold standard for comparison for respiratory syncytial virus detection. Using ProFlu Plus as a gold standard, RT-PCR/ESI-MS had sensitivity and specificity of 82.1% (23/28) and 100% (258/258), respectively, for Influenza A, 100% (16/16) and 99.6% (269/270), respectively for Influenza B, and 88.6% (39/44) and 99.6% (241/242) for any Influenza virus. Using matching results from ProFlu Plus and Xpert Flu as a gold standard, RT-PCR/ESI-MS had 85.2% (23/27) and 100% (259/259) sensitivity and specificity respectively for Influenza A, 100% (14/14) and 99.6% (270/272), respectively for Influenza B virus. Overall, RT-PCR/ESI-MS was not as sensitive as the combined gold standard of ProFlu Plus and Xpert Flu, although it has the capability of detecting other respiratory viruses.",,"['Hardick, Justin', 'Dugas, Andrea', 'Goheen, Joshua', 'Rothman, Richard', 'Gaydos, Charlotte']",,,,
,PMC,Innate immune restriction and antagonism of viral RNA lacking 2′-O methylation,http://dx.doi.org/10.1016/j.virol.2015.01.019,PMC4424151,,,"N-7 and 2′-O methylation of host cell mRNA occurs in the nucleus and results in the generation of cap structures (cap 0, m(7)GpppN; cap 1, m(7)GpppNm) that control gene expression by modulating nuclear export, splicing, turnover, and protein synthesis. Remarkably, RNA cap modification also contributes to mammalian cell host defense as viral RNA lacking 2′-O methylation are sensed and inhibited by IFIT1, an interferon (IFN) stimulated gene (ISG). Accordingly, pathogenic viruses that replicate in the cytoplasm have evolved mechanisms to circumvent IFIT1 restriction and facilitate infection of mammalian cells. These include: (a) generating cap 1 structures on their RNA through cap-snatching or virally-encoded 2′-O methyltransferases, (b) using cap-independent means of translation, or (c) using RNA secondary structural motifs to antagonize IFIT1 binding. This review will discuss new insights as to how specific modifications at the 5′-end of viral RNA modulate host pathogen recognition responses to promote infection and disease.",,"['Hyde, Jennifer L.', 'Diamond, Michael S.']",,,,
,PMC,The host immune dynamics of pneumococcal colonization: Implications for novel vaccine development,http://dx.doi.org/10.4161/21645515.2014.979631,PMC4514076,,,"The human nasopharynx (NP) microbiota is complex and diverse and Streptococcus pneumoniae (pneumococcus) is a frequent member. In the first few years of life, children experience maturation of their immune system thereby conferring homeostatic balance in which pneumococci are typically rendered as harmless colonizers in the upper respiratory environment. Pneumococcal carriage declines in many children before they acquire capsular-specific antibodies, suggesting a capsule antibody-independent mechanism of natural protection against pneumococcal carriage in early childhood. A child's immune system in the first few years of life is Th2-skewed so as to avoid inflammation-induced immunopathology. Understanding Th1/Th2 and Th17 ontogeny in early life and how adjuvant vaccine formulations shift the balance of T helper-cell differentiation, may facilitate the development of new protein-based pneumococcal vaccines. This article will discuss the immune dynamics of pneumococcal colonization in infants. The discussion aims to benefit the design and improvement of protein subunit-based next-generation pneumococcal vaccines.",,"['Khan, M Nadeem', 'Pichichero, Michael E']",,,,
,PMC,Some Chinese folk prescriptions for wind-cold type common cold,http://dx.doi.org/10.1016/j.jtcme.2014.11.035,PMC4488566,26151024,CC BY-NC-ND,"Although self-limiting, the common cold (感冒gǎn mào) is highly prevalent. There are no effective antivirals to cure the common cold and few effective measures to prevent it, However, for thousands years, Chinese people have treated the common cold with natural herbs, According to the traditional Chinese medicine (TCM) theory (中醫理論 zhōng yī lǐ lùn), the common cold is considered as an exterior syndrome, which can be further divided into the wind-cold type (風寒型 fēng hán xíng), the wind-heat type (風熱型 fēng rè xíng), and the summer heat dampness type (暑熱型 shǔ rè xíng). Since the most common type of common cold caught in winter and spring is the wind-cold type, the article introduced some Chinese folk prescriptions for the wind-cold type common cold with normal and weak physique, respectively. For thousands of years, Chinese folk prescriptions for the common cold, as complementary and alternative medicine (CAM; 補充與替代醫學 bǔ chōng yǔ tì dài yī xué), have been proven to be effective, convenient, cheap, and most importantly, safe. The Chinese folk prescriptions (中國民間處方 zhōng guó mín jiān chǔ fāng) for the wind-cold type common cold are quite suitable for general practitioners or patients with the wind-cold type common cold, to treat the disease. Of course, their pharmacological features and mechanisms of action need to be further studied.",2015 Feb 10,"['Hai-long, Zhai', 'Shimin, Chen', 'Yalan, Lu']",J Tradit Complement Med,,,
,PMC,Inducible nitric oxide synthase (iNOS) regulatory region variation in non-human primates,http://dx.doi.org/10.1016/j.meegid.2015.01.015,PMC4361290,,,"Inducible nitric oxide synthase (iNOS) is an enzyme that plays a key role in intracellular immune response against respiratory infections. Since various species of nonhuman primates exhibit different levels of susceptibility to infectious respiratory diseases, and since variation in regulatory regions of genes is thought to play a key role in expression levels of genes, two candidate regulatory regions of iNOS were mapped, sequenced, and compared across five species of nonhuman primates: African green monkeys (chlorocebus sabeus), pig-tailed macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis), Indian rhesus macaques (Macaca mulatta), and Chinese rhesus macaques (M. mulatta). In addition, we conducted an in silico analysis of the transcription factor binding sites associated with genetic variation in these two candidate regulatory regions across species. We found that only one of the two candidate regions showed strong evidence of involvement in iNOS regulation. Specifically, we found evidence of 13 conserved binding site candidates linked to iNOS regulation: AP-1, C/EBPB, CREB, GATA-1, GATA-3, NF-AT, NF-AT5, NF-κB, KLF4, Oct-1, PEA3, SMAD3, and TCF11. Additionally, we found evidence of interspecies variation in binding sites for several regulatory elements linked to iNOS (GATA-3, GATA-4, KLF6, SRF, STAT-1, STAT-3, OLF-1 and HIF-1) across species, especially in African green monkeys relative to other species. Given the key role of iNOS in respiratory immune response, the findings of this study might help guide the direction of future studies aimed to uncover the molecular mechanisms underlying the increased susceptibility of African green monkeys to several viral and bacterial respiratory infections.",,"['Roodgar, Morteza', 'Ross, Cody T.', 'Kenyon, Nicholas J.', 'Marcelino, Gretchen', 'Smith, David Glenn']",,,,
,PMC,Hyperoxia downregulates angiotensin-converting enzyme-2 in human fetal lung fibroblasts,http://dx.doi.org/10.1038/pr.2015.27,PMC5119454,,,"BACKGROUND: Angiotensin (ANG) II is involved in experimental hyperoxia-induced lung fibrosis. Angiotensin-converting enzyme-2 (ACE-2) degrades ANG II and is thus protective, but is downregulated in adult human and experimental lung fibrosis. Hyperoxia is a known cause of chronic fibrotic lung disease in neonates, but the role of ACE-2 in neonatal lung fibrosis is unknown. We hypothesized that ACE-2 in human fetal lung cells might be downregulated by hyperoxic gas. METHODS: Fetal human lung fibroblast IMR90 cells were exposed to hyperoxic (95% O(2)/5% CO(2)) or normoxic (21% O(2)/5% CO(2)) gas in vitro. Cells and culture media were recovered separately for assays of ACE-2 enzymatic activity, mRNA, and immunoreactive protein. RESULTS: Hyperoxia decreased ACE-2 immunoreactive protein and enzyme activity in IMR90 cells (both P < 0.01), but did not change ACE-2 mRNA. ACE-2 protein was increased in the cell supernatant, suggesting protease-mediated ectodomain shedding. TAPI-2, an inhibitor of TNF-α–converting enzyme (TACE/ADAM17), prevented both the decrease in cellular ACE-2 and the increase in soluble ACE-2 (both P < 0.05). CONCLUSION: These data show that ACE-2 is expressed in fetal human lung fibroblasts but is significantly decreased by hyperoxic gas. They also suggest that hyperoxia decreases ACE-2 through a shedding mechanism mediated by ADAM17/TACE.",,"['Oarhe, Chinyere I.', 'Dang, Vinh', 'Dang, MyTrang', 'Nguyen, Hang', 'Gopallawa, Indiwari', 'Gewolb, Ira H.', 'Uhal, Bruce D.']",,,,
,PMC,Protease Inhibitors Targeting Coronavirus and Filovirus Entry,http://dx.doi.org/10.1016/j.antiviral.2015.01.011,PMC4774534,,,"In order to gain entry into cells, diverse viruses, including Ebola virus, SARS-coronavirus and the emerging MERS-coronavirus, depend on activation of their envelope glycoproteins by host cell proteases. The respective enzymes are thus excellent targets for antiviral intervention. In cell culture, activation of Ebola virus, as well as SARS- and MERS-coronavirus can be accomplished by the endosomal cysteine proteases, cathepsin L (CTSL) and cathepsin B (CTSB). In addition, SARS- and MERS-coronavirus can use serine proteases localized at the cell surface, for their activation. However, it is currently unclear which protease(s) facilitate viral spread in the infected host. We report here that the cysteine protease inhibitor K11777, ((2S)-N-[(1E,3S)-1-(benzenesulfonyl)-5-phenylpent-1-en-3-yl]-2-{[(E)-4-methylpiperazine-1-carbonyl]amino}-3-phenylpropanamide) and closely-related vinylsulfones act as broad-spectrum antivirals by targeting cathepsin-mediated cell entry. K11777 is already in advanced stages of development for a number of parasitic diseases, such as Chagas disease, and has proven to be safe and effective in a range of animal models. K11777 inhibition of SARS-CoV and Ebola virus entry was observed in the sub-nanomolar range. In order to assess, whether cysteine or serine proteases promote viral spread in the host, we compared the antiviral activity of an optimized K11777-derivative with that of camostat, an inhibitor of TMPRSS2 and related serine proteases. Employing a pathogenic animal model of SARS-CoV infection, we demonstrated that viral spread and pathogenesis of SARS-CoV is driven by serine rather than cysteine proteases and can be effectively prevented by camostat. Camostat has been clinically used to treat chronic pancreatitis, and thus represents an exciting potential therapeutic for respiratory coronavirus infections. Our results indicate that camostat, or similar serine protease inhibitors, might be an effective option for treatment of SARS and potentially MERS, while vinyl sulfone-based inhibitors are excellent lead candidates for Ebola virus therapeutics.",,"['Zhou, Yanchen', 'Vedantham, Punitha', 'Lu, Kai', 'Agudelo, Juliet', 'Carrion, Ricardo', 'Nunneley, Jerritt W.', 'Barnard, Dale', 'Pöhlmann, Stefan', 'McKerrow, James H.', 'Renslo, Adam R.', 'Simmons, Graham']",,,,
,PMC,ACE and ACE2 in kidney disease,http://dx.doi.org/10.5527/wjn.v4.i1.74,PMC4317630,,,"Renin angiotensin system (RAS) activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme (ACE)-angiotensin II (Ang II)-Ang II type 1 (AT1) axis is considered to control the effects of RAS activation on renal disease. However, since its discovery in 2000 ACE2 has also been demonstrated to have a significant impact on the RAS. The synthesis and catabolism of Ang II are regulated via a complex series of interactions, which involve ACE and ACE2. In the kidneys, ACE2 is expressed in the proximal tubules and less strongly in the glomeruli. The synthesis of inactive Ang 1-9 from Ang I and the catabolism of Ang II to produce Ang 1-7 are the main functions of ACE2. Ang 1-7 reduces vasoconstriction, water retention, salt intake, cell proliferation, and reactive oxygen stress, and also has a renoprotective effect. Thus, in the non-classical RAS the ACE2-Ang 1-7-Mas axis counteracts the ACE-Ang II-AT1 axis. This review examines recent human and animal studies about renal ACE and ACE2.",,"['Mizuiri, Sonoo', 'Ohashi, Yasushi']",,,,
,PMC,miR-122 Stimulates Hepatitis C Virus RNA Synthesis by Altering the Balance of Viral RNAs Engaged in Replication Versus Translation,http://dx.doi.org/10.1016/j.chom.2014.12.014,PMC4326553,,,"The liver-specific microRNA, miR-122, stabilizes hepatitis C virus (HCV) RNA genomes by recruiting host argonaute 2 (AGO2) to the 5′ end and preventing decay mediated by exonuclease Xrn1. However, HCV replication requires miR-122 in Xrn1-depleted cells, indicating additional function s. We show that miR-122 enhances HCV RNA levels by altering the fraction of HCV genomes available for RNA synthesis. Exogenous miR-122 increases viral RNA and protein levels in Xrn1-depleted cells, with enhanced RNA synthesis occurring before heightened protein synthesis. Inhibiting protein translation blocks miR-122-mediated increases in RNA synthesis, but independently enhances RNA synthesis by releasing ribosomes from viral genomes. Additionally, miR-122 reduces the fraction of viral genomes engaged in protein translation. Depleting AGO2 or PCBP2, which binds HCV RNA in competition with miR-122 and promotes translation, eliminates miR-122 stimulation of RNA synthesis. Thus, by displacing PCBP2, miR-122 reduces HCV genomes engaged in translation while increasing the fraction available for RNA synthesis.",,"['Masaki, Takahiro', 'Arend, Kyle C.', 'Li, You', 'Yamane, Daisuke', 'McGivern, David R.', 'Kato, Takanobu', 'Wakita, Takaji', 'Moorman, Nathaniel J.', 'Lemon, Stanley M.']",,,,
,PMC,Stress Granule Components G3BP1 and G3BP2 Play a Proviral Role Early in Chikungunya Virus Replication,http://dx.doi.org/10.1128/JVI.03612-14,PMC4442398,,,"Stress granules (SGs) are protein-mRNA aggregates that are formed in response to environmental stresses, resulting in translational inhibition. SGs are generally believed to play an antiviral role and are manipulated by many viruses, including various alphaviruses. GTPase-activating protein (SH3 domain)-binding protein 1 (G3BP1) is a key component and commonly used marker of SGs. Its homolog G3BP2 is a less extensively studied SG component. Here, we demonstrate that Chikungunya virus (CHIKV) infection induces cytoplasmic G3BP1- and G3BP2-containing granules that differ from bona fide SGs in terms of morphology, composition, and behavior. For several Old World alphaviruses it has been shown that nonstructural protein 3 (nsP3) interacts with G3BPs, presumably to inhibit SG formation, and we have confirmed this interaction in CHIKV-infected cells. Surprisingly, CHIKV also relied on G3BPs for efficient replication, as simultaneous depletion of G3BP1 and G3BP2 reduced viral RNA levels, CHIKV protein expression, and viral progeny titers. The G3BPs colocalized with CHIKV nsP2 and nsP3 in cytoplasmic foci, but no colocalization with nsP1, nsP4, or dsRNA was observed. Furthermore, G3BPs could not be detected in a cellular fraction enriched for CHIKV replication/transcription complexes, suggesting that they are not directly involved in CHIKV RNA synthesis. Depletion of G3BPs did not affect viral entry, translation of incoming genomes, or nonstructural polyprotein processing but resulted in severely reduced levels of negative-stranded (and consequently also positive-stranded) RNA. This suggests a role for the G3BPs in the switch from translation to genome amplification, although the exact mechanism by which they act remains to be explored. IMPORTANCE Chikungunya virus (CHIKV) causes a severe polyarthritis that has affected millions of people since its reemergence in 2004. The lack of approved vaccines or therapeutic options and the ongoing explosive outbreak in the Caribbean underline the importance of better understanding CHIKV replication. Stress granules (SGs) are cytoplasmic protein-mRNA aggregates formed in response to various stresses, including viral infection. The RNA-binding proteins G3BP1 and G3BP2 are essential SG components. SG formation and the resulting translational inhibition are generally considered an antiviral response, and many viruses manipulate or block this process. Late in infection, we and others have observed CHIKV nonstructural protein 3 in cytoplasmic G3BP1- and G3BP2-containing granules. These virally induced foci differed from true SGs and did not appear to represent replication complexes. Surprisingly, we found that G3BP1 and G3BP2 were also needed for efficient CHIKV replication, likely by facilitating the switch from translation to genome amplification early in infection.",,"['Scholte, Florine E. M.', 'Tas, Ali', 'Albulescu, Irina C.', 'Žusinaite, Eva', 'Merits, Andres', 'Snijder, Eric J.', 'van Hemert, Martijn J.']",,,,
,PMC,Glycosylation of Mouse DPP4 Plays a Role in Inhibiting Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/JVI.03445-14,PMC4442375,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes dipeptidyl peptidase 4 (DPP4) as an entry receptor. Mouse DPP4 (mDPP4) does not support MERS-CoV entry; however, changes at positions 288 and 330 can confer permissivity. Position 330 changes the charge and glycosylation state of mDPP4. We show that glycosylation is a major factor impacting DPP4 receptor function. These results provide insight into DPP4 species-specific differences impacting MERS-CoV host range and may inform MERS-CoV mouse model development.",,"['Peck, Kayla M.', 'Cockrell, Adam S.', 'Yount, Boyd L.', 'Scobey, Trevor', 'Baric, Ralph S.', 'Heise, Mark T.']",,,,
,PMC,Chimeric Rhinoviruses Obtained via Genetic Engineering or Artificially Induced Recombination Are Viable Only if the Polyprotein Coding Sequence Derives from the Same Species,http://dx.doi.org/10.1128/JVI.03668-14,PMC4442373,,,"Recombination is a widespread phenomenon that ensures both the stability and variation of RNA viruses. This phenomenon occurs with different frequencies within species of the Enterovirus genus. Intraspecies recombination is described frequently among non-rhinovirus enteroviruses but appears to be sporadic in rhinoviruses. Interspecies recombination is even rarer for rhinoviruses and mostly is related to ancient events which contributed to the speciation of these viruses. We reported that artificially engineered 5′ untranslated region (UTR) interspecies rhinovirus/rhinovirus or rhinovirus/non-rhinovirus enterovirus recombinants are fully viable. Using a similar approach, we demonstrated in this study that exchanges of the P1-2A polyprotein region between members of the same rhinovirus species, but not between members of different species, give rise to competent chimeras. To further assess the rhinovirus intra- and interspecies recombination potential, we used artificially induced recombination by cotransfection of 5′-end-deleted and 3′-end-deleted and replication-deficient genomes. In this system, intraspecies recombination also resulted in viable viruses with high frequency, whereas no interspecies rhinovirus recombinants could be recovered. Mapping intraspecies recombination sites within the polyprotein highlighted recombinant hotspots in nonstructural genes and at gene boundaries. Notably, all recombinants occurring at gene junctions presented in-frame sequence duplications, whereas most intragenic recombinants were homologous. Taken together, our results suggest that only intraspecies recombination gives rise to viable rhinovirus chimeras in the polyprotein coding region and that recombination hotspots map to nonstructural genes with in-frame duplications at gene boundaries. These data provide new insights regarding the mechanism and limitations of rhinovirus recombination. IMPORTANCE Recombination represents a means to ensure both the stability and the variation of RNA viruses. While intraspecies recombination is described frequently among non-rhinovirus enteroviruses, it seems to occur more rarely in rhinoviruses. Interspecies recombination is even rarer in this virus group and is mostly related to ancient events, which contributed to its speciation. We used engineered chimeric genomes and artificially induced RNA recombination to study experimentally the recombination potential of rhinoviruses and analyze recombination sites. Our results suggest that only intraspecies recombination gives rise to viable chimeras in the polyprotein coding region. Furthermore, characterization of intraspecies chimeras provides new insight into putative recombination hotspots within the polyprotein. In summary, we applied two powerful and complementary experimental approaches to improve current knowledge on rhinovirus recombination.",,"['Schibler, Manuel', 'Piuz, Isabelle', 'Hao, Weidong', 'Tapparel, Caroline']",,,,
,PMC,ATP1A1-Mediated Src Signaling Inhibits Coronavirus Entry into Host Cells,http://dx.doi.org/10.1128/JVI.03274-14,PMC4442369,,,"In addition to transporting ions, the multisubunit Na(+),K(+)-ATPase also functions by relaying cardiotonic steroid (CTS)-binding-induced signals into cells. In this study, we analyzed the role of Na(+),K(+)-ATPase and, in particular, of its ATP1A1 α subunit during coronavirus (CoV) infection. As controls, the vesicular stomatitis virus (VSV) and influenza A virus (IAV) were included. Using gene silencing, the ATP1A1 protein was shown to be critical for infection of cells with murine hepatitis virus (MHV), feline infectious peritonitis virus (FIPV), and VSV but not with IAV. Lack of ATP1A1 did not affect virus binding to host cells but resulted in inhibited entry of MHV and VSV. Consistently, nanomolar concentrations of the cardiotonic steroids ouabain and bufalin, which are known not to affect the transport function of Na(+),K(+)-ATPase, inhibited infection of cells with MHV, FIPV, Middle East respiratory syndrome (MERS)-CoV, and VSV, but not IAV, when the compounds were present during virus inoculation. Cardiotonic steroids were shown to inhibit entry of MHV at an early stage, resulting in accumulation of virions close to the cell surface and, as a consequence, in reduced fusion. In agreement with an early block in infection, the inhibition of VSV by CTSs could be bypassed by low-pH shock. Viral RNA replication was not affected when these compounds were added after virus entry. The antiviral effect of ouabain could be relieved by the addition of different Src kinase inhibitors, indicating that Src signaling mediated via ATP1A1 plays a crucial role in the inhibition of CoV and VSV infections. IMPORTANCE Coronaviruses (CoVs) are important pathogens of animals and humans, as demonstrated by the recent emergence of new human CoVs of zoonotic origin. Antiviral drugs targeting CoV infections are lacking. In the present study, we show that the ATP1A1 subunit of Na(+),K(+)-ATPase, an ion transporter and signaling transducer, supports CoV infection. Targeting ATP1A1 either by gene silencing or by low concentrations of the ATP1A1-binding cardiotonic steroids ouabain and bufalin resulted in inhibition of infection with murine, feline, and MERS-CoVs at an early entry stage. Infection with the control virus VSV was also inhibited. Src signaling mediated by ATP1A1 was shown to play a crucial role in the inhibition of virus entry by ouabain and bufalin. These results suggest that targeting the Na(+),K(+)-ATPase using cardiotonic steroids, several of which are FDA-approved compounds, may be an attractive therapeutic approach against CoV and VSV infections.",,"['Burkard, Christine', 'Verheije, Monique H.', 'Haagmans, Bart L.', 'van Kuppeveld, Frank J.', 'Rottier, Peter J. M.', 'Bosch, Berend-Jan', 'de Haan, Cornelis A. M.']",,,,
,PMC,"Knowledge, Attitudes, and Practices Regarding Avian Influenza A (H7N9) Among Mobile Phone Users: A Survey in Zhejiang Province, China",http://dx.doi.org/10.2196/mhealth.3394,PMC4342637,25653213,CC BY,"BACKGROUND: Understanding people’s knowledge, attitudes, and practices (KAP) regarding a new infectious disease is crucial to the prevention and control of it. Human infection with avian influenza A (H7N9) was first identified on March 31, 2013 in China. Out of the total number of 134 cases confirmed from March to September 2013 in China, Zhejiang Province saw the greatest number (46 cases). OBJECTIVE: This study employed a mobile Internet survey to assess KAP regarding H7N9 among mobile phone users in Zhejiang Province. This study intended to examine KAP by region and the association between sociodemographic variables and KAP. METHODS: An anonymous questionnaire was designed by Zhejiang Provincial Center for Disease Control and Prevention (CDC). A cross-sectional survey was executed through a mobile Internet application platform of China Unicom in 5 regions in Zhejiang Province. Stratified and clustered sampling methods were applied and mobile phone users were invited to participate in the study voluntarily. RESULTS: A total of 9582 eligible mobile phone users participated in the survey with a response rate of 1.92% (9582/5,000,000). A total of 9105 valid responses (95.02%) were included for statistical analysis. Generally, more than three-quarters of the participants had some basic knowledge of H7N9 and held the attitude recommended by the Zhejiang CDC toward eating cooked poultry (77.55%, 7061/9105) and visiting a hospital at the occurrence of symptoms (78.51%, 7148/9105). Approximately half of the participants worried about contracting H7N9, and took preventive practices recommended by the Zhejiang CDC. But only 14.29% (1301/9105) of participants kept eating cooked poultry as usual. Although worry about H7N9 infection did not differ by region, Hangzhou saw the largest proportion of participants with knowledge of H7N9, which was probably because Hangzhou had the greatest number of H7N9 cases. KAP varied by some sociodemographic variables. Female participants were more likely to know about symptoms of H7N9 (OR 1.32, 95% CI 1.08-1.61), to worry about contracting it (OR 1.15, 95% CI 1.04-1.27), and to report their lives being influenced by it (OR 1.27, 95% CI 1.15-1.41). They were also more likely to take the recommended precautions. Male participants and younger participants were less likely to comply with advocated protective practices. CONCLUSIONS: The results suggest that health education should be customized depending on sociodemographic variables to achieve more effective behavioral outcomes.",2015 Feb 4,"['Gu, Hua', 'Jiang, Zhenggang', 'Chen, Bin', 'Zhang, Jueman (Mandy)', 'Wang, Zhengting', 'Wang, Xinyi', 'Cai, Jian', 'Chen, Yongdi', 'Zheng, Dawei', 'Jiang, Jianmin']",JMIR Mhealth Uhealth,,,
,PMC,Simulations Show that Virus Assembly and Budding Are Facilitated by Membrane Microdomains,http://dx.doi.org/10.1016/j.bpj.2014.12.017,PMC4317536,,,"For many viruses, assembly and budding occur simultaneously during virion formation. Understanding the mechanisms underlying this process could promote biomedical efforts to block viral propagation and enable use of capsids in nanomaterials applications. To this end, we have performed molecular dynamics simulations on a coarse-grained model that describes virus assembly on a fluctuating lipid membrane. Our simulations show that the membrane can promote association of adsorbed subunits through dimensional reduction, but it also introduces thermodynamic and kinetic effects that can inhibit complete assembly. We find several mechanisms by which membrane microdomains, such as lipid rafts, reduce these effects, and thus, enhance assembly. We show how these predicted mechanisms can be experimentally tested. Furthermore, the simulations demonstrate that assembly and budding depend crucially on the system dynamics via multiple timescales related to membrane deformation, protein diffusion, association, and adsorption onto the membrane.",,"['Ruiz-Herrero, Teresa', 'Hagan, Michael\xa0F.']",,,,
,PMC,CXCL9 Is Important for Recruiting Immune T Cells into the Brain and Inducing an Accumulation of the T Cells to the Areas of Tachyzoite Proliferation to Prevent Reactivation of Chronic Cerebral Infection with Toxoplasma gondii,http://dx.doi.org/10.1016/j.ajpath.2014.10.003,PMC4305179,,,"T cells are required to maintain the latency of chronic infection with Toxoplasma gondii in the brain. Here, we examined the role of non–glutamic acid-leucine-arginine CXC chemokine CXCL9 for T-cell recruitment to prevent reactivation of infection with T. gondii. Severe combined immunodeficient (SCID) mice were infected and treated with sulfadiazine to establish a chronic infection. Immune T cells from infected wild-type mice were transferred into the SCID mice in combination with treatment with anti-CXCL9 or control sera. Three days later, sulfadiazine was discontinued to initiate reactivation of infection. Numbers of CD4(+) and CD8(+) T cells isolated from the brains were markedly less in mice treated with anti-CXCL9 serum than in mice treated with control serum at 3 days after sulfadiazine discontinuation. Amounts of tachyzoite (acute stage form of T. gondii)-specific SAG1 mRNA and numbers of foci associated with tachyzoites were significantly greater in the former than the latter at 5 days after sulfadiazine discontinuation. An accumulation of CD3(+) T cells into the areas of tachyzoite growth was significantly less frequent in the SCID mice treated with anti-CXCL9 serum than in mice treated with control serum. These results indicate that CXCL9 is crucial for recruiting immune T cells into the brain and inducing an accumulation of the T cells into the areas where tachyzoites proliferate to prevent reactivation of chronic T. gondii infection.",,"['Ochiai, Eri', 'Sa, Qila', 'Brogli, Morgan', 'Kudo, Tomoya', 'Wang, Xisheng', 'Dubey, Jitender P.', 'Suzuki, Yasuhiro']",,,,
,PMC,Optimal Design of Non-equilibrium Experiments for Genetic Network Interrogation,http://dx.doi.org/10.1016/j.aml.2014.09.013,PMC4281269,,,"Many experimental systems in biology, especially synthetic gene networks, are amenable to perturbations that are controlled by the experimenter. We developed an optimal design algorithm that calculates optimal observation times in conjunction with optimal experimental perturbations in order to maximize the amount of information gained from longitudinal data derived from such experiments. We applied the algorithm to a validated model of a synthetic Brome Mosaic Virus (BMV) gene network and found that optimizing experimental perturbations may substantially decrease uncertainty in estimating BMV model parameters.",,"['Adoteye, Kaska', 'Banks, H.T.', 'Flores, Kevin B.']",,,,
,PMC,Adapting High-Throughput Screening Methods and Assays for Biocontainment Laboratories,http://dx.doi.org/10.1089/adt.2014.617,PMC4340648,,,"High-throughput screening (HTS) has been integrated into the drug discovery process, and multiple assay formats have been widely used in many different disease areas but with limited focus on infectious agents. In recent years, there has been an increase in the number of HTS campaigns using infectious wild-type pathogens rather than surrogates or biochemical pathogen-derived targets. Concurrently, enhanced emerging pathogen surveillance and increased human mobility have resulted in an increase in the emergence and dissemination of infectious human pathogens with serious public health, economic, and social implications at global levels. Adapting the HTS drug discovery process to biocontainment laboratories to develop new drugs for these previously uncharacterized and highly pathogenic agents is now feasible, but HTS at higher biosafety levels (BSL) presents a number of unique challenges. HTS has been conducted with multiple bacterial and viral pathogens at both BSL-2 and BSL-3, and pilot screens have recently been extended to BSL-4 environments for both Nipah and Ebola viruses. These recent successful efforts demonstrate that HTS can be safely conducted at the highest levels of biological containment. This review outlines the specific issues that must be considered in the execution of an HTS drug discovery program for high-containment pathogens. We present an overview of the requirements for HTS in high-level biocontainment laboratories.",,"['Rasmussen, Lynn', 'Tigabu, Bersabeh', 'White, E. Lucile', 'Bostwick, Robert', 'Tower, Nichole', 'Bukreyev, Alexander', 'Rockx, Barry', 'LeDuc, James W.', 'Noah, James W.']",,,,
,PMC,The first case of porcine epidemic diarrhea in Canada,,PMC4298265,,,"In January, 2014, increased mortality was reported in piglets with acute diarrhea on an Ontario farm. Villus atrophy in affected piglets was confined to the small intestine. Samples of colon content were PCR-positive for porcine epidemic diarrhea virus (PEDV). Other laboratory tests did not detect significant pathogens, confirming this was the first case of PED in Canada.",,"['Ojkic, Davor', 'Hazlett, Murray', 'Fairles, Jim', 'Marom, Anna', 'Slavic, Durda', 'Maxie, Grant', 'Alexandersen, Soren', 'Pasick, John', 'Alsop, Janet', 'Burlatschenko, Sue']",,,,
,PMC,Enterovirus 71 mediates cell cycle arrest in S phase through non-structural protein 3D,http://dx.doi.org/10.4161/15384101.2014.980631,PMC4353240,,,"Many viruses disrupt the host cell cycle to facilitate their own growth. We assessed the mechanism and function of enterovirus 71 (EV71), a primary causative agent for recent hand, foot, and mouth disease outbreaks, in manipulating cell cycle progression. Our results suggest that EV71 infection induces S-phase arrest in diverse cell types by preventing the cell cycle transition from the S phase into the G2/M phase. Similar results were observed for an alternate picornavirus, Coxsackievirus A16. Synchronization in S phase, but not G0/G1 phase or G2/M phase, promotes viral replication. Consistent with its ability to arrest cells in S phase, the expression of cyclin A2, CDK 2, cyclin E1, and cyclin B1 was regulated by EV71 through increasing transcription of cyclin E1, promoting proteasome-mediated degradation of cyclin A2 and regulating the phosphorylation of CDK 2. Finally, a non-structural protein of EV71, the RNA-dependent RNA polymerase 3D, was demonstrated to mediate S-phase cell cycle arrest. These findings suggest that EV71 induces S-phase cell cycle arrest in infected cells via non-structural protein 3D, which may provide favorable conditions for virus production.",,"['Yu, Jinghua', 'Zhang, Liying', 'Ren, Peiyou', 'Zhong, Ting', 'Li, Zhaolong', 'Wang, Zengyan', 'Li, Jingliang', 'Liu, Xin', 'Zhao, Ke', 'Zhang, Wenyan', 'Yu, Xiao-Fang']",,,,
,PMC,Importance of Viruses in Acute Otitis Media,http://dx.doi.org/10.1097/MOP.0000000000000184,PMC4383320,,,"PURPOSE OF REVIEW: Acute otitis media (AOM) occurs as a complication of viral upper respiratory tract infection (URI). Bacterial otopathogens and respiratory viruses interact and play important roles in AOM development. Better understanding of viral and bacterial interactions may lead to innovative ways to lessen the burden of this common childhood disease. RECENT FINDINGS: There has been increasing evidence that AOM occurs during URI, even in the absence of nasopharyngeal bacterial colonization. Among the types of viruses associated with AOM, respiratory syncytial virus continues to be the most commonly detected. It is still unclear whether viral load plays an important role in AOM development, but symptomatic URI (as opposed to asymptomatic viral infection) is crucial. Widespread use of bacterial and viral vaccines in young children, including pneumococcal conjugate and influenza vaccines, has led to the reduction in otitis media-related health care use between 2001 and 2011. There has been no new vaccine against respiratory viruses other than influenza. SUMMARY: Progress has been made towards reduction of the burden of AOM in the last decade. Success in reducing AOM incidence will rely mainly on prevention of nasopharyngeal otopathogen colonization, as well as reduction in the incidence of viral URI.",,"['Nokso-Koivisto, Johanna', 'Marom, Tal', 'Chonmaitree, Tasnee']",,,,
,PMC,Transcriptional regulation of secretory capacity by bZip transcription factors,http://dx.doi.org/10.1007/s11515-014-1338-7,PMC4374484,,,"Cells of specialized secretory organs expand their secretory pathways to accommodate the increased protein load necessary for their function. The endoplasmic reticulum (ER), the Golgi apparatus and the secretory vesicles, expand not only the membrane components but also the protein machinery required for increased protein production and transport. Increased protein load causes an ER stress response akin to the Unfolded Protein Response (UPR). Recent work has implicated several bZip transcription factors in the regulation of protein components of the early secretory pathway necessary to alleviate this stress. Here, we highlight eight bZip transcription factors in regulating secretory pathway component genes. These include components of the three canonical branches of the UPR–ATF4, XBP1, and ATF6, as well as the five members of the Creb3 family of transcription factors. We review findings from both invertebrate and vertebrate model systems suggesting that all of these proteins increase secretory capacity in response to increased protein load. Finally, we propose that the Creb3 family of factors may have a dual role in secretory cell differentiation by also regulating the pathways necessary for cell cycle exit during terminal differentiation.",,"['FOX, Rebecca M.', 'ANDREW, Deborah J.']",,,,
,PMC,Surveillance of acute respiratory infections among outpatients: A pilot study in Isfahan city,,PMC4400703,25983761,CC BY-NC-SA,"BACKGROUND: Considering that there was not any regional survey in Isfahan, Iran regarding the epidemiology of acute respiratory tract infections (ARTI) in different age groups of general population, the aim of this study was to determine the epidemiologic feature of ARTIs in Isfahan using multiplex polymerase chain reaction (PCR) method. MATERIALS AND METHODS: In this cross-sectional study, patients aged <80 years with symptoms of ARTI were studied, during 2009-2010 Nasopharyngeal and dry throat swab specimens were collected and pathogens of ARTI was determined using multiplex real-time PCR. RESULTS: In this study, 455 cases with ARTI were studied. Mean age of studied population was 29.9 ± 18.5 (range: 0.2-80). Symptoms such as sore throat (86.3%), coryza (68.0%) and dry cough (54.3%) were the most common symptoms in all studied groups, whereas fever was the most clinical presentation of younger patients (<15 years old) and headache and skeletal pain were the most common symptoms of older patients (>15 years old). Rhinovirus was the most common cause of ARTI in patients aged <5 years and those aged >50 years. Influenza virus B was the most common cause of ARTI in patients aged 5-50 years. CONCLUSION: Our study provides baseline information on the epidemiologic and clinical feature of outpatients with ARTIs in Isfahan city. Though our findings in this pilot study could be helpful in diagnosis, treatment, and prevention of ARTI, planning preventive interventional.",2015 Feb,"['Javadi, Abbasali', 'Adibi, Peyman', 'Ataei, Behrooz', 'Nokhodian, Zary', 'Yaran, Majid']",J Res Med Sci,,,
,PMC,Pneumomediastinum,http://dx.doi.org/10.3978/j.issn.2072-1439.2015.01.11,PMC4332083,,,"Pneumomediastinum is a condition in which air is present in the mediastinum. This condition can result from physical trauma or other situations that lead to air escaping from the lungs, airways or bowel into the chest cavity. Pneumomediastinum is a rare situation and occurs when air leaks into the mediastinum. The diagnosis can be confirmed via chest X-ray or CT scanning of the thorax. The main symptom is usually severe central chest pain. Other symptoms include laboured breathing, voice distortion (as with helium) and subcutaneous emphysema, specifically affecting the face, neck, and chest. Pneumomediastinum can also be characterized by the shortness of breath that is typical of a respiratory system problem. It is often recognized on auscultation by a ""crunching"" sound timed with the cardiac cycle (Hamman’s crunch). Pnemomediastinum may also present with symptoms mimicking cardiac tamponade as a result of the increased intrapulmonary pressure on venous flow to the heart. The tissues in the mediastinum will slowly resorb the air in the cavity so most pneumomediastinums are treated conservatively.",,"['Kouritas, Vasileios K.', 'Papagiannopoulos, Konstantinos', 'Lazaridis, George', 'Baka, Sofia', 'Mpoukovinas, Ioannis', 'Karavasilis, Vasilis', 'Lampaki, Sofia', 'Kioumis, Ioannis', 'Pitsiou, Georgia', 'Papaiwannou, Antonis', 'Karavergou, Anastasia', 'Kipourou, Maria', 'Lada, Martha', 'Organtzis, John', 'Katsikogiannis, Nikolaos', 'Tsakiridis, Kosmas', 'Zarogoulidis, Konstantinos', 'Zarogoulidis, Paul']",,,,
,PMC,Neuroinfectious Diseases: A Crisis in Neurology and a Call for Action,http://dx.doi.org/10.1001/jamaneurol.2014.3442,PMC5267936,,,,,"Nath, Avindra",,,,
,PMC,Development and Characterization of Neutralizing Monoclonal Antibodies Against the S1 Subunit Protein of QX-like Avian Infectious Bronchitis Virus Strain Sczy3,http://dx.doi.org/10.1089/mab.2014.0081,PMC4350142,,,"Infectious bronchitis (IB) is a highly contagious disease in chickens caused by infectious bronchitis virus (IBV). The present study was carried out with the aim to develop anti-spike 1 (S1) subunit monoclonal antibodies (MAbs) that could react with IBV strains of different genotypes. The high antigenicity region of S1 gene of an QX-like IBV strain Sczy3 was amplified and ligated into the prokaryotic expression vector pET-32a(+), and the recombinant His-S1 fusion proteins were expressed and purified. The purified whole viral antigen of Sczy3 strain was used to immunize BALB/c mice to produce hybridoma-secreting anti-IBV MAbs. Eleven anti-IBV MAbs were generated, and two MAbs 1C8 and 2C10 were positive in indirect ELISA against both His-S1 protein and the purified whole viral antigen. These two MAbs showed positive reaction with IBV in Western blot, and the isotype were both IgM. These two MAbs react specifically with IBV but not with Newcastle disease virus (NDV) or avian influenza virus (AIV) subtype H9 or H5, and could cross-react with other 10 IBV strains in five different genotypes. End-point neutralizing assay performed in chicken embro kidney (CEK) cells revealed that the neutralization titer of 1C8 and 2C10 against Sczy3 reached 1:2.82 and 1:4.70, respectively. The anti-S1 MAbs produced in the present work may be valuable in developing an antigen-capture ELISA test for antigen detection or a competitive ELISA test for antibody detection or therapeutic medicine for IB in poultry.",,"['Zou, Nianli', 'Wang, Fuyan', 'Duan, Zhenzhen', 'Xia, Jing', 'Wen, Xintian', 'Yan, Qigui', 'Liu, Ping', 'Cao, Sanjie', 'Huang, Yong']",,,,
,PMC,Monoclonal Antibody to N Protein of Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.1089/mab.2014.0062,PMC4350141,,,"The N gene of porcine epidemic diarrhea virus (PEDV) was amplified by RT-PCR using specific primers, and inserted into the expression vector pCold-I to construct a recombinant plasmid pCold-I-N. The recombinant plasmid was expressed in Escherichia coli BL21 (DE3) under IPTG induction. Then, female BALB/c mice were immunized with the purified recombinant N protein and one strain of hybridoma cells named 2B8 secreting anti-N protein monoclonal antibodies (MAb) was obtained by hybridoma technique. The MAb was specifically reacted with PEDV and identified by Western blot and indirect immunofluorescence assays. This work indicated that the MAb would be a valuable tool as a specific diagnostic reagent for PEDV epidemiological surveys and diagnosis in the future.",,"['Pan, Xi', 'Kong, Ning', 'Shan, Tongling', 'Zheng, Hao', 'Tong, Wu', 'Yang, Shen', 'Li, Guoxin', 'Zhou, Enmin', 'Tong, Guangzhi']",,,,
,PMC,"Immunology careers at the NIH, FDA and CDC: different paths that focus on advancing public health",http://dx.doi.org/10.1038/ni.3061,PMC5830109,,,"The NIH, FDA and CDC offer a wide spectrum of job opportunities focused on improving public health through the discovery and translation of research, the regulation of safe and effective medicines, and the protection of health security.",,"['Catalfamo, Marta', 'Mawle, Alison', 'Verthelyi, Daniela']",,,,
,PMC,Ebola virus disease: Managing a practice challenge with evidence,http://dx.doi.org/10.1097/01.NUMA.0000460047.32427.16,PMC4406246,,,,,"['Matlock, Ann Marie', 'Gutierrez, Debbie C.', 'Wallen, Gwenyth R.']",,,,
,PMC,"Effectiveness of early cardiology undergraduate learning using simulation on retention, application of learning and level of confidence during clinical clerkships",http://dx.doi.org/10.11622/smedj.2015023,PMC4350465,,,"INTRODUCTION: This study aimed to assess the effectiveness of the use of a cardiopulmonary patient simulator in the teaching of second-year medical students. Effectiveness was measured in terms of the extent of knowledge retention and students’ ability to apply the skills learned in subsequent real-life patient contact. METHODS: In this study, ten third-year medical students who had previously undergone simulator training as part of their second-year curriculum underwent an objective structured clinical examination (OSCE) and a multiple-choice question (MCQ) test to assess their ability to apply the knowledge gained during the simulator training when dealing with real patients. The performance of this group of students was compared with that of a group of ten fourth-year medical students who did not undergo simulation training. RESULTS: Although the third-year medical students performed well in the OSCE, they were outperformed by the group of fourth-year medical students, who had an extra year of clinical exposure. The MCQ scores of the two groups of students were similar. Post-simulation training survey revealed that students were generally in favour of incorporating cardiopulmonary simulator training in the preclinical curriculum. CONCLUSION: Cardiopulmonary simulator training is a useful tool for the education of preclinical medical students. It aids the translation of preclinical knowledge into real-life clinical skills.",,"['Lin, Weiqin', 'Lee, Glenn K', 'Loh, Joshua P', 'Tay, Edgar L', 'Sia, Winnie', 'Lau, Tang-Ching', 'Hooi, Shing-Chuan', 'Poh, Kian-Keong']",,,,
,PMC,Multiple Circulating Infections Can Mimic the Early Stages of Viral Hemorrhagic Fevers and Possible Human Exposure to Filoviruses in Sierra Leone Prior to the 2014 Outbreak,http://dx.doi.org/10.1089/vim.2014.0108,PMC4287116,,,"Lassa fever (LF) is a severe viral hemorrhagic fever caused by Lassa virus (LASV). The LF program at the Kenema Government Hospital (KGH) in Eastern Sierra Leone currently provides diagnostic services and clinical care for more than 500 suspected LF cases per year. Nearly two-thirds of suspected LF patients presenting to the LF Ward test negative for either LASV antigen or anti-LASV immunoglobulin M (IgM), and therefore are considered to have a non-Lassa febrile illness (NLFI). The NLFI patients in this study were generally severely ill, which accounts for their high case fatality rate of 36%. The current studies were aimed at determining possible causes of severe febrile illnesses in non-LF cases presenting to the KGH, including possible involvement of filoviruses. A seroprevalence survey employing commercial enzyme-linked immunosorbent assay tests revealed significant IgM and IgG reactivity against dengue virus, chikungunya virus, West Nile virus (WNV), Leptospira, and typhus. A polymerase chain reaction–based survey using sera from subjects with acute LF, evidence of prior LASV exposure, or NLFI revealed widespread infection with Plasmodium falciparum malaria in febrile patients. WNV RNA was detected in a subset of patients, and a 419 nt amplicon specific to filoviral L segment RNA was detected at low levels in a single patient. However, 22% of the patients presenting at the KGH between 2011 and 2014 who were included in this survey registered anti-Ebola virus (EBOV) IgG or IgM, suggesting prior exposure to this agent. The 2014 Ebola virus disease (EVD) outbreak is already the deadliest and most widely dispersed outbreak of its kind on record. Serological evidence reported here for possible human exposure to filoviruses in Sierra Leone prior to the current EVD outbreak supports genetic analysis that EBOV may have been present in West Africa for some time prior to the 2014 outbreak.",,"['Boisen, Matthew L.', 'Schieffelin, John S.', 'Goba, Augustine', 'Oottamasathien, Darin', 'Jones, Abigail B.', 'Shaffer, Jeffrey G.', 'Hastie, Kathryn M.', 'Hartnett, Jessica N.', 'Momoh, Mambu', 'Fullah, Mohammed', 'Gabiki, Michael', 'Safa, Sidiki', 'Zandonatti, Michelle', 'Fusco, Marnie', 'Bornholdt, Zach', 'Abelson, Dafna', 'Gire, Stephen K.', 'Andersen, Kristian G.', 'Tariyal, Ridhi', 'Stremlau, Mathew', 'Cross, Robert W.', 'Geisbert, Joan B.', 'Pitts, Kelly R.', 'Geisbert, Thomas W.', 'Kulakoski, Peter', 'Wilson, Russell B.', 'Henderson, Lee', 'Sabeti, Pardis C.', 'Grant, Donald S.', 'Garry, Robert F.', 'Saphire, Erica O.', 'Branco, Luis M.', 'Khan, Sheik Humarr']",,,,
,PMC,RIG-I-like receptor regulation in virus infection and immunity,http://dx.doi.org/10.1016/j.coviro.2015.01.004,PMC5076476,,,"Mammalian cells have the intrinsic capacity to detect viral pathogens and to initiate an antiviral response that is characterized by the induction of interferons (IFNs) and proinflammatory cytokines. A delicate regulation of the signaling pathways that lead to cytokine production is needed to ensure effective clearance of the virus, while preventing tissue damage caused by excessive cytokine release. Here, we focus on the mechanisms that modulate the signal transduction triggered by RIG-I-like receptors (RLRs) and their adaptor protein MAVS, key components of the host machinery for sensing foreign RNA. Specifically, we summarize recent advances in understanding how RLR signaling is regulated by posttranslational and posttranscriptional mechanisms, microRNAs (miRNAs) and autophagy. We further discuss how viruses target these regulatory mechanisms for immune evasion.",,"['Chan, Ying Kai', 'Gack, Michaela U']",,,,
,PMC,Superiority of Transcriptional Profiling Over Procalcitonin for Distinguishing Bacterial From Viral Lower Respiratory Tract Infections in Hospitalized Adults,http://dx.doi.org/10.1093/infdis/jiv047,PMC4565998,,,"Background. Distinguishing between bacterial and viral lower respiratory tract infection (LRTI) remains challenging. Transcriptional profiling is a promising tool for improving diagnosis in LRTI. Methods. We performed whole blood transcriptional analysis in 118 patients (median age [interquartile range], 61 [50–76] years) hospitalized with LRTI and 40 age-matched healthy controls (median age, 60 [46–70] years). We applied class comparisons, modular analysis, and class prediction algorithms to identify and validate diagnostic biosignatures for bacterial and viral LRTI. Results. Patients were classified as having bacterial (n = 22), viral (n = 71), or bacterial-viral LRTI (n = 25) based on comprehensive microbiologic testing. Compared with healthy controls, statistical group comparisons (P < .01; multiple-test corrections) identified 3376 differentially expressed genes in patients with bacterial LRTI, 2391 in viral LRTI, and 2628 in bacterial-viral LRTI. Patients with bacterial LRTI showed significant overexpression of inflammation and neutrophil genes (bacterial > bacterial-viral > viral), and those with viral LRTI displayed significantly greater overexpression of interferon genes (viral > bacterial-viral > bacterial). The K–nearest neighbors algorithm identified 10 classifier genes that discriminated between bacterial and viral LRTI with a 95% sensitivity (95% confidence interval, 77%–100%) and 92% specificity (77%–98%), compared with a sensitivity of 38% (18%–62%) and a specificity of 91% (76%–98%) for procalcitonin. Conclusions. Transcriptional profiling is a helpful tool for diagnosis of LRTI.",,"['Suarez, Nicolas M.', 'Bunsow, Eleonora', 'Falsey, Ann R.', 'Walsh, Edward E.', 'Mejias, Asuncion', 'Ramilo, Octavio']",,,,
,PMC,Common and distinctive localization patterns of Crumbs polarity complex proteins in the mammalian eye,http://dx.doi.org/10.1016/j.gep.2015.01.002,PMC5033123,,,"Crumbs polarity complex proteins are essential for cellular and tissue polarity, and for adhesion of epithelial cells. In epithelial tissues deletion of any of three core proteins disrupts localization of the other proteins, indicating structural and functional interdependence among core components. Despite previous studies of function and co-localization that illustrated the properties that these proteins share, it is not known whether an individual component of the complex plays a distinct role in a unique cellular and developmental context. In order to investigate this question, we primarily used confocal imaging to determine the expression and subcellular localization of the core Crumbs polarity complex proteins during ocular development. Here we show that in developing ocular tissues core Crumbs polarity complex proteins, Crb, Pals1 and Patj, generally appear in an overlapping pattern with some exceptions. All three core complex proteins localize to the apical junction of the retinal and lens epithelia. Pals1 is also localized in the Golgi of the retinal cells and Patj localizes to the nuclei of the apically located subset of progenitor cells. These findings suggest that core Crumbs polarity complex proteins exert common and independent functions depending on cellular context.",,"['Kim, Jin Young', 'Song, Ji Yun', 'Karnam, Santi', 'Park, Jun Young', 'Lee, Jamie JH', 'Kim, Seonhee', 'Cho, Seo-Hee']",,,,
,PMC,Species-Specific Transmission of Novel Picornaviruses in Lemurs,http://dx.doi.org/10.1128/JVI.03342-14,PMC4403396,,,"The roles of host genetics versus exposure and contact frequency in driving cross-species transmission remain the subject of debate. Here, we used a multitaxon lemur collection at the Saint Louis Zoo in the United States as a model to gain insight into viral transmission in a setting of high interspecies contact. Lemurs are a diverse and understudied group of primates that are highly endangered. The speciation of lemurs, which are endemic to the island of Madagascar, occurred in geographic isolation apart from that of continental African primates. Although evidence of endogenized viruses in lemur genomes exists, no exogenous viruses of lemurs have been described to date. Here we identified two novel picornaviruses in fecal specimens of ring-tailed lemurs (Lemur catta) and black-and-white ruffed lemurs (Varecia variegata). We found that the viruses were transmitted in a species-specific manner (lesavirus 1 was detected only in ring-tailed lemurs, while lesavirus 2 was detected only in black-and-white ruffed lemurs). Longitudinal sampling over a 1-year interval demonstrated ongoing infection in the collection. This was supported by evidence of viral clearance in some animals and new infections in previously uninfected animals, including a set of newly born triplets that acquired the infection. While the two virus strains were found to be cocirculating in a mixed-species exhibit of ring-tailed lemurs, black-and-white ruffed lemurs, and black lemurs, there was no evidence of cross-species transmission. This suggests that despite high-intensity contact, host species barriers can prevent cross-species transmissions of these viruses. IMPORTANCE Up to 75% of emerging infectious diseases in humans today are the result of zoonotic transmission. However, a challenge in understanding transmission dynamics has been the limited models of cross-species transmission. Zoos provide a unique opportunity to explore parameters defining viral transmission. We demonstrated that ongoing virus transmission in a mixed lemur species exhibit was species specific. This suggests that despite high contact intensity, host species barriers contribute to protection from cross-species transmission of these viruses. While the combinations of species might differ, most zoological parks worldwide commonly feature mixed-species exhibits. Collectively, this report demonstrates a widely applicable approach toward understanding infectious disease transmission.",,"['Lim, Efrem S.', 'Deem, Sharon L.', 'Porton, Ingrid J.', 'Cao, Song', 'Wang, David']",,,,
,PMC,Antiviral Potential of ERK/MAPK and PI3K/AKT/mTOR Signaling Modulation for Middle East Respiratory Syndrome Coronavirus Infection as Identified by Temporal Kinome Analysis,http://dx.doi.org/10.1128/AAC.03659-14,PMC4335870,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus, and infections with this virus can result in acute respiratory syndrome with renal failure. Globally, MERS-CoV has been responsible for 877 laboratory-confirmed infections, including 317 deaths, since September 2012. As there is a paucity of information regarding the molecular pathogenesis associated with this virus or the identities of novel antiviral drug targets, we performed temporal kinome analysis on human hepatocytes infected with the Erasmus isolate of MERS-CoV with peptide kinome arrays. bioinformatics analysis of our kinome data, including pathway overrepresentation analysis (ORA) and functional network analysis, suggested that extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphoinositol 3-kinase (PI3K)/serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling responses were specifically modulated in response to MERS-CoV infection in vitro throughout the course of infection. The overrepresentation of specific intermediates within these pathways determined by pathway and functional network analysis of our kinome data correlated with similar patterns of phosphorylation determined through Western blot array analysis. In addition, analysis of the effects of specific kinase inhibitors on MERS-CoV infection in tissue culture models confirmed these cellular response observations. Further, we have demonstrated that a subset of licensed kinase inhibitors targeting the ERK/MAPK and PI3K/AKT/mTOR pathways significantly inhibited MERS-CoV replication in vitro whether they were added before or after viral infection. Taken together, our data suggest that ERK/MAPK and PI3K/AKT/mTOR signaling responses play important roles in MERS-CoV infection and may represent novel drug targets for therapeutic intervention strategies.",,"['Kindrachuk, Jason', 'Ork, Britini', 'Hart, Brit J.', 'Mazur, Steven', 'Holbrook, Michael R.', 'Frieman, Matthew B.', 'Traynor, Dawn', 'Johnson, Reed F.', 'Dyall, Julie', 'Kuhn, Jens H.', 'Olinger, Gene G.', 'Hensley, Lisa E.', 'Jahrling, Peter B.']",,,,
,PMC,STING Agonists Induce an Innate Antiviral Immune Response against Hepatitis B Virus,http://dx.doi.org/10.1128/AAC.04321-14,PMC4335851,,,"Chronicity of hepatitis B virus (HBV) infection is due to the failure of a host to mount a sufficient immune response to clear the virus. The aim of this study was to identify small-molecular agonists of the pattern recognition receptor (PRR)-mediated innate immune response to control HBV infection. To achieve this goal, a coupled mouse macrophage and hepatocyte culture system mimicking the intrahepatic environment was established and used to screen small-molecular compounds that activate macrophages to produce cytokines, which in turn suppress HBV replication in a hepatocyte-derived stable cell line supporting HBV replication in a tetracycline-inducible manner. An agonist of the mouse stimulator of interferon (IFN) genes (STING), 5,6-dimethylxanthenone-4-acetic acid (DMXAA), was found to induce a robust cytokine response in macrophages that efficiently suppressed HBV replication in mouse hepatocytes by reducing the amount of cytoplasmic viral nucleocapsids. Profiling of cytokines induced by DMXAA and agonists of representative Toll-like receptors (TLRs) in mouse macrophages revealed that, unlike TLR agonists that induced a predominant inflammatory cytokine/chemokine response, the STING agonist induced a cytokine response dominated by type I IFNs. Moreover, as demonstrated in an HBV hydrodynamic mouse model, intraperitoneal administration of DMXAA significantly induced the expression of IFN-stimulated genes and reduced HBV DNA replication intermediates in the livers of mice. This study thus proves the concept that activation of the STING pathway induces an antiviral cytokine response against HBV and that the development of small-molecular human STING agonists as immunotherapeutic agents for treatment of chronic hepatitis B is warranted.",,"['Guo, Fang', 'Han, Yanxing', 'Zhao, Xuesen', 'Wang, Jianghua', 'Liu, Fei', 'Xu, Chunxiao', 'Wei, Lai', 'Jiang, Jian-Dong', 'Block, Timothy M.', 'Guo, Ju-Tao', 'Chang, Jinhong']",,,,
,PMC,Network representations of immune system complexity,http://dx.doi.org/10.1002/wsbm.1288,PMC4339634,,,"The mammalian immune system is a dynamic multi-scale system composed of a hierarchically organized set of molecular, cellular and organismal networks that act in concert to promote effective host defense. These networks range from those involving gene regulatory and protein-protein interactions underlying intracellular signaling pathways and single cell responses to increasingly complex networks of in vivo cellular interaction, positioning and migration that determine the overall immune response of an organism. Immunity is thus not the product of simple signaling events but rather non-linear behaviors arising from dynamic, feedback-regulated interactions among many components. One of the major goals of systems immunology is to quantitatively measure these complex multi-scale spatial and temporal interactions, permitting development of computational models that can be used to predict responses to perturbation. Recent technological advances permit collection of comprehensive datasets at multiple molecular and cellular levels while advances in network biology support representation of the relationships of components at each level as physical or functional interaction networks. The latter facilitate effective visualization of patterns and recognition of emergent properties arising from the many interactions of genes, molecules, and cells of the immune system. We illustrate the power of integrating ‘omics’ and network modeling approaches for unbiased reconstruction of signaling and transcriptional networks with a focus on applications involving the innate immune system. We further discuss future possibilities for reconstruction of increasingly complex cellular and organism-level networks and development of sophisticated computational tools for prediction of emergent immune behavior arising from the concerted action of these networks.",,"['Subramanian, Naeha', 'Torabi-Parizi, Parizad', 'Gottschalk, Rachel A.', 'Germain, Ronald N.', 'Dutta, Bhaskar']",,,,
,PMC,Clinical presentation and microbiological diagnosis in paediatric respiratory tract infection: a systematic review,http://dx.doi.org/10.3399/bjgp15X683497,PMC4325442,,,"BACKGROUND: Antibiotic prescribing decisions for respiratory tract infection (RTI) in primary care could be improved if clinicians could target bacterial infections. However, there are currently no evidence-based diagnostic rules to identify microbial aetiology in children presenting with acute RTIs. AIM: To analyse evidence of associations between clinical symptoms or signs and detection of microbes from the upper respiratory tract (URT) of children with acute cough. DESIGN AND SETTING: Systematic review and meta-analysis. METHOD: A literature search identified articles reporting relationships between individual symptoms and/or signs, and microbes detected from URT samples. Associations between pathogens and symptoms or signs were summarised, and meta-analysis conducted where possible. RESULTS: There were 9984 articles identified, of which 28 met inclusion criteria. Studies identified 30 symptoms and 41 signs for 23 microbes, yielding 1704 potential associations, of which only 226 (13%) have presently been investigated. Of these, relevant statistical analyses were presented for 175 associations, of which 25% were significant. Meta-analysis demonstrated significant relationships between respiratory syncytial virus (RSV) detection and chest retractions (pooled odds ratio [OR] 1.9, 95% confidence interval [CI] = 1.6 to 2.3), wheeze (pooled OR 1.7, 95% CI = 1.5 to 2.0), and crepitations/crackles (pooled OR 1.7, 95% CI = 1.3 to 2.2). CONCLUSIONS: There was an absence of evidence for URT pathogens other than RSV. The meta-analysis identified clinical signs associated with RSV detection, suggesting clinical presentation may offer some, albeit poor, diagnostic value. Further research is urgently needed to establish the value of symptoms and signs in determining microbiological aetiology and improve targeting of antibiotics in primary care.",,"['Thornton, Hannah V', 'Blair, Peter S', 'Lovering, Andrew M', 'Muir, Peter', 'Hay, Alastair D']",,,,
,PMC,The 5' and 3' ends of alphavirus RNAs – non-coding is not non-functional,http://dx.doi.org/10.1016/j.virusres.2015.01.016,PMC4654126,,,"The non-coding regions found at the 5' and 3' ends of alphavirus genomes regulate viral gene expression, replication, translation and virus-host interactions, which have significant implications for viral evolution, host range, and pathogenesis. The functions of these non-coding regions are mediated by a combination of linear sequence and structural elements. The capped 5' untranslated region (UTR) contains promoter elements, translational regulatory sequences that modulate dependence on cellular translation factors, and structures that help to avoid innate immune defenses. The polyadenylated 3' UTR contains highly conserved sequence elements for viral replication, binding sites for cellular miRNAs that determine cell tropism, host range, and pathogenesis, and conserved binding regions for a cellular protein that influences viral RNA stability. Nonetheless, there are additional conserved elements in non-coding regions of the virus (e.g., the repeated sequence elements in the 3' UTR) whose function remains obscure. Thus, key questions remain as to the function of these short yet influential untranslated segments of alphavirus RNAs.",,"['Hyde, Jennifer L.', 'Chen, Rubing', 'Trobaugh, Derek W.', 'Diamond, Michael S.', 'Weaver, Scott C.', 'Klimstra, William B.', 'Wilusz, Jeffrey']",,,,
,PMC,Detection of Viruses By Counting Single Fluorescent Genetically Biotinylated Reporter Immunophage Using a Lateral Flow Assay,http://dx.doi.org/10.1021/am5082556,PMC4334444,,,"We demonstrated a lateral flow immunoassay (LFA) for detection of viruses using fluorescently-labeled M13 bacteriophage as reporters and single-reporter counting as the readout. AviTag-biotinylated M13 phage were functionalized with antibodies using avidin-biotin conjugation and fluorescently labeled with AlexaFluor 555. Individual phage bound to target viruses (here MS2 as a model) captured on an LFA membrane strip were imaged using epi-fluorescence microscopy. Using automated image processing, we counted the number of bound phage in micrographs as a function of target concentration. The resultant assay was more sensitive than enzyme-linked immunosorbent assays and traditional colloidal-gold nanoparticle LFAs for direct detection of viruses.",,"['Kim, Jinsu', 'Adhikari, Meena', 'Dhamane, Sagar', 'Hagström, Anna E. V.', 'Kourentzi, Katerina', 'Strych, Ulrich', 'Willson, Richard C.', 'Conrad, Jacinta C.']",,,,
,PMC,The Role of Interferon-λ Locus Polymorphisms in Hepatitis C and Other Infectious Diseases,http://dx.doi.org/10.1159/000369902,PMC6738896,,,"Since its discovery in 2003, the type III interferon-λ (IFN-λ) family has been found to contribute significantly to the host response to infection. Whilst IFN-λ shares many features with type I IFN induction and signalling pathways, the tissue-specific restricted expression of its receptor, IL28RA, makes IFN-λ a major mediator of host innate immunity in tissues and organs with a high epithelial cell content. Host susceptibility and responses to infection are known to be heterogeneous, and the identification of common genetic variants linked to disease outcome by genome-wide association studies (GWAS) has underscored the significance of host polymorphisms in responses to infection. Several such GWAS have highlighted the IFN-λ locus on chromosome 19q13 as an area of genetic variation significantly associated with hepatitis C virus (HCV) infection, and the rs12979860 genotype can be used in clinical practice as a biomarker for predicting a successful response to treatment with pegylated IFN and ribavarin. Here, we discuss IFN-λ genetic polymorphisms and their role in HCV and other infectious diseases as well as their potential impact on clinical diagnostics, patient stratification and therapy. Finally, the broader role of IFN-λ in the immunopathogenesis of non-infectious inflammatory diseases is considered.",,"['Griffiths, Samantha J.', 'Dunnigan, Cory M.', 'Russell, Clark D.', 'Haas, Jürgen G.']",,,,
,PMC,The Effect of Species Representation on the Detection of Positive Selection in Primate Gene Data Sets,http://dx.doi.org/10.1093/molbev/msu399,PMC4379402,,,"Over evolutionary time, both host- and virus-encoded genes have been continually selected to modify their interactions with one another. This has resulted in the rapid evolution of the specific codons that govern the physical interactions between host and virus proteins. Virologists have discovered that these evolutionary signatures, acquired in nature, can provide a shortcut in the functional dissection of host–virus interactions in the laboratory. However, the use of evolution studies in this way is complicated by the fact that many nonhuman primate species are endangered, and biomaterials are often difficult to acquire. Here, we assess how the species representation in primate gene data sets affects the detection of positive natural selection. Our results demonstrate how targeted primate sequencing projects could greatly enhance research in immunology, virology, and beyond.",,"['McBee, Ross M.', 'Rozmiarek, Shea A.', 'Meyerson, Nicholas R.', 'Rowley, Paul A.', 'Sawyer, Sara L.']",,,,
,PMC,Study of viral pathogenesis in humanized mice,http://dx.doi.org/10.1016/j.coviro.2015.01.002,PMC4456257,,,"Many of the viral pathogens that cause infectious disease in humans have a highly restricted species tropism, making the study of their pathogenesis and the development of clinical therapies difficult. The improvement of humanized mouse models over the past 30 years has greatly facilitated researchers’ abilities to study host responses to viral infections in a cost effective and ethical manner. From HIV to hepatotropic viruses to Middle East respiratory syndrome coronavirus, humanized mice have led to the identification of factors crucial to the viral life cycle, an outlet for testing candidate therapies, and improved analysis of human immune responses to infection. In tackling both the new and old viruses as they emerge, humanized mice will continue to be an indispensable tool.",,"['Gaska, Jenna M.', 'Ploss, Alexander']",,,,
,PMC,Structural View and Substrate Specificity of Papain-like Protease from Avian Infectious Bronchitis Virus,http://dx.doi.org/10.1074/jbc.M114.628636,PMC4358136,,,"Papain-like protease (PLpro) of coronaviruses (CoVs) carries out proteolytic maturation of non-structural proteins that play a role in replication of the virus and performs deubiquitination of host cell factors to scuttle antiviral responses. Avian infectious bronchitis virus (IBV), the causative agent of bronchitis in chicken that results in huge economic losses every year in the poultry industry globally, encodes a PLpro. The substrate specificities of this PLpro are not clearly understood. Here, we show that IBV PLpro can degrade Lys(48)- and Lys(63)-linked polyubiquitin chains to monoubiquitin but not linear polyubiquitin. To explain the substrate specificities, we have solved the crystal structure of PLpro from IBV at 2.15-Å resolution. The overall structure is reminiscent of the structure of severe acute respiratory syndrome CoV PLpro. However, unlike the severe acute respiratory syndrome CoV PLpro that lacks blocking loop (BL) 1 of deubiquitinating enzymes, the IBV PLpro has a short BL1-like loop. Access to a conserved catalytic triad consisting of Cys(101), His(264), and Asp(275) is regulated by the flexible BL2. A model of ubiquitin-bound IBV CoV PLpro brings out key differences in substrate binding sites of PLpros. In particular, P3 and P4 subsites as well as residues interacting with the β-barrel of ubiquitin are different, suggesting different catalytic efficiencies and substrate specificities. We show that IBV PLpro cleaves peptide substrates KKAG-7-amino-4-methylcoumarin and LRGG-7-amino-4-methylcoumarin with different catalytic efficiencies. These results demonstrate that substrate specificities of IBV PLpro are different from other PLpros and that IBV PLpro might target different ubiquitinated host factors to aid the propagation of the virus.",,"['Kong, Lingying', 'Shaw, Neil', 'Yan, Lingming', 'Lou, Zhiyong', 'Rao, Zihe']",,,,
,PMC,High Secretion of Interferons by Human Plasmacytoid Dendritic Cells upon Recognition of Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.03607-14,PMC4403407,,,"The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as the causative agent of a severe respiratory disease with a fatality rate of approximately 30%. The high virulence and mortality rate prompted us to analyze aspects of MERS-CoV pathogenesis, especially its interaction with innate immune cells such as antigen-presenting cells (APCs). Particularly, we analyzed secretion of type I and type III interferons (IFNs) by APCs, i.e., B cells, macrophages, monocyte-derived/myeloid dendritic cells (MDDCs/mDCs), and by plasmacytoid dendritic cells (pDCs) of human and murine origin after inoculation with MERS-CoV. Production of large amounts of type I and III IFNs was induced exclusively in human pDCs, which were significantly higher than IFN induction by severe acute respiratory syndrome (SARS)-CoV. Of note, IFNs were secreted in the absence of productive replication. However, receptor binding, endosomal uptake, and probably signaling via Toll-like receptor 7 (TLR7) were critical for sensing of MERS-CoV by pDCs. Furthermore, active transcription of MERS-CoV N RNA and subsequent N protein expression were evident in infected pDCs, indicating abortive infection. Taken together, our results point toward dipeptidyl peptidase 4 (DPP4)-dependent endosomal uptake and subsequent infection of human pDCs by MERS-CoV. However, the replication cycle is stopped after early gene expression. In parallel, human pDCs are potent IFN-producing cells upon MERS-CoV infection. Knowledge of such IFN responses supports our understanding of MERS-CoV pathogenesis and is critical for the choice of treatment options. IMPORTANCE MERS-CoV causes a severe respiratory disease with high fatality rates in human patients. Recently, confirmed human cases have increased dramatically in both number and geographic distribution. Understanding the pathogenesis of this highly pathogenic CoV is crucial for developing successful treatment strategies. This study elucidates the interaction of MERS-CoV with APCs and pDCs, particularly the induction of type I and III IFN secretion. Human pDCs are the immune cell population sensing MERS-CoV but secrete significantly larger amounts of IFNs, especially IFN-α, than in response to SARS-CoV. A model for molecular virus-host interactions is presented outlining IFN induction in pDCs. The massive IFN secretion upon contact suggests a critical role of this mechanism for the high degree of immune activation observed during MERS-CoV infection.",,"['Scheuplein, Vivian A.', 'Seifried, Janna', 'Malczyk, Anna H.', 'Miller, Lilija', 'Höcker, Lena', 'Vergara-Alert, Júlia', 'Dolnik, Olga', 'Zielecki, Florian', 'Becker, Björn', 'Spreitzer, Ingo', 'König, Renate', 'Becker, Stephan', 'Waibler, Zoe', 'Mühlebach, Michael D.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronaviruses with Mutations in the E Protein Are Attenuated and Promising Vaccine Candidates,http://dx.doi.org/10.1128/JVI.03566-14,PMC4403406,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) causes a respiratory disease with a mortality rate of 10%. A mouse-adapted SARS-CoV (SARS-CoV-MA15) lacking the envelope (E) protein (rSARS-CoV-MA15-ΔE) is attenuated in vivo. To identify E protein regions and host responses that contribute to rSARS-CoV-MA15-ΔE attenuation, several mutants (rSARS-CoV-MA15-E*) containing point mutations or deletions in the amino-terminal or the carboxy-terminal regions of the E protein were generated. Amino acid substitutions in the amino terminus, or deletion of regions in the internal carboxy-terminal region of E protein, led to virus attenuation. Attenuated viruses induced minimal lung injury, diminished limited neutrophil influx, and increased CD4(+) and CD8(+) T cell counts in the lungs of BALB/c mice, compared to mice infected with the wild-type virus. To analyze the host responses leading to rSARS-CoV-MA15-E* attenuation, differences in gene expression elicited by the native and mutant viruses in the lungs of infected mice were determined. Expression levels of a large number of proinflammatory cytokines associated with lung injury were reduced in the lungs of rSARS-CoV-MA15-E*-infected mice, whereas the levels of anti-inflammatory cytokines were increased, both at the mRNA and protein levels. These results suggested that the reduction in lung inflammation together with a more robust antiviral T cell response contributed to rSARS-CoV-MA15-E* attenuation. The attenuated viruses completely protected mice against challenge with the lethal parental virus, indicating that these viruses are promising vaccine candidates. IMPORTANCE Human coronaviruses are important zoonotic pathogens. SARS-CoV caused a worldwide epidemic infecting more than 8,000 people with a mortality of around 10%. Therefore, understanding the virulence mechanisms of this pathogen and developing efficacious vaccines are of high importance to prevent epidemics from this and other human coronaviruses. Previously, we demonstrated that a SARS-CoV lacking the E protein was attenuated in vivo. Here, we show that small deletions and modifications within the E protein led to virus attenuation, manifested by minimal lung injury, limited neutrophil influx to the lungs, reduced expression of proinflammatory cytokines, increased anti-inflammatory cytokine levels, and enhanced CD4(+) and CD8(+) T cell counts in vivo, suggesting that these phenomena contribute to virus attenuation. The attenuated mutants fully protected mice from challenge with virulent virus. These studies show that mutations in the E protein are not well tolerated and indicate that this protein is an excellent target for vaccine development.",,"['Regla-Nava, Jose A.', 'Nieto-Torres, Jose L.', 'Jimenez-Guardeño, Jose M.', 'Fernandez-Delgado, Raul', 'Fett, Craig', 'Castaño-Rodríguez, Carlos', 'Perlman, Stanley', 'Enjuanes, Luis', 'DeDiego, Marta L.']",,,,
,PMC,A Single Herpesvirus Protein Can Mediate Vesicle Formation in the Nuclear Envelope,http://dx.doi.org/10.1074/jbc.M114.627521,PMC4358120,,,"Herpesviruses assemble capsids in the nucleus and egress by unconventional vesicle-mediated trafficking through the nuclear envelope. Capsids bud at the inner nuclear membrane into the nuclear envelope lumen. The resulting intralumenal vesicles fuse with the outer nuclear membrane, delivering the capsids to the cytoplasm. Two viral proteins are required for vesicle formation, the tail-anchored pUL34 and its soluble interactor, pUL31. Whether cellular proteins are involved is unclear. Using giant unilamellar vesicles, we show that pUL31 and pUL34 are sufficient for membrane budding and scission. pUL34 function can be bypassed by membrane tethering of pUL31, demonstrating that pUL34 is required for pUL31 membrane recruitment but not for membrane remodeling. pUL31 can inwardly deform membranes by oligomerizing on their inner surface to form buds that constrict to vesicles. Therefore, a single viral protein can mediate all events necessary for membrane budding and abscission.",,"['Lorenz, Michael', 'Vollmer, Benjamin', 'Unsay, Joseph D.', 'Klupp, Barbara G.', 'García-Sáez, Ana J.', 'Mettenleiter, Thomas C.', 'Antonin, Wolfram']",,,,
,PMC,A Novel Tuberculosis Antigen Identified from Human Tuberculosis Granulomas,http://dx.doi.org/10.1074/mcp.M114.045237,PMC4390254,,,"Tuberculosis is a global infectious disease caused by Mycobacterium tuberculosis (Mtb). Although novel Mtb biomarkers from both the pathogen and host have been studied, more breakthroughs are still needed to meet different clinic requirements. In an effort to identify Mtb antigens, chaperone-peptide complexes were purified from TB infected lungs using free-solution isoelectric focusing combined with high resolution LTQ Orbitrap Velos mass spectrometry. Antigen specific cellular immune responses in vitro were then examined. Those efforts led to the identification of six Mtb peptides only identified in Tuberculosis lung samples and that were not found in the control samples. Additionally, antigen-specific IFN-γ secretion, T-cell proliferation, cytokine expression, and a cytotoxic assay were also evaluated. Among the peptides isolated, we identified a 34 amino acid peptide named PKA(p) belonging to a serine/threonine–protein kinase, as being able to generate Mtb-specific cellular immune responses as noted by elevated antigen-specific cytokine secretion levels, increased CD8(+) T-cell proliferation and a strong cytotoxic lymphocyte (CTL) response. Moreover, the immune stimulating abilities of PKA(p) were further validated in vivo, with target peptide immunized mice showing an increased cellular IFN-γ in both the lungs and spleen without causing immunopathogenesis. In conclusion, we identified novel functional Mtb antigens directly from the granulomatous lesions of Tuberculosis patients, inducing not only significant antigen-specific IFN-γ secretion but also a marked cytotoxic lymphocyte functional response. These findings indicated that PKA(p) has potential as a novel antigen biomarker for vaccine development.",,"['Yu, Yang', 'Jin, Dongdong', 'Hu, Shizong', 'Zhang, Yan', 'Zheng, Xiaojing', 'Zheng, Jianhua', 'Liao, Mingfeng', 'Chen, Xinchun', 'Graner, Michael', 'Liu, Haiying', 'Jin, Qi']",,,,
,PMC,Exploratory studies on the therapeutic effects of Kumarabharana Rasa in the management of chronic tonsillitis among children at a tertiary care hospital of Karnataka,http://dx.doi.org/10.1016/j.jtcme.2014.11.031,PMC4738038,26870676,CC BY-NC-ND,"The effect of an Ayurvedic poly-herbo-mineral formulation Kumarabharana Rasa (KR) in the management of chronic tonsillitis (Tundikeri) in children has been assessed in this study. This clinical study was a double-arm study with a pre- and post-test design at the outpatient level in a tertiary Ayurveda hospital attached to a teaching institute located in district headquarters in Southern India. Patients (n = 40) with chronic tonsillitis satisfying diagnostic criteria and aged between 5 and 10 years were selected from the outpatient Department of Kaumarbhritya, SDM College of Ayurveda and Hospital, Hassan. Among them, 20 patients were treated with Kumarabharana rasa (tablet form) at a dose of 500 mg once daily for 30 days (Group A). The other 20 patients were treated with Godhuma Vati (placebo) at a dose of 500 mg once daily for 30 days (Group B). In both groups, Madhu was the Anupana advised. After completion of 30 days of treatment, the patients were assessed on the following day and another investigation took place 15 days later. Statistically significant effects (p < 0.05) in the reduction of all signs and symptoms of chronic tonsillitis after KR treatment were observed. These results indicate that Kumarabharana Rasa has an ameliorative effect in reducing the signs and symptoms of chronic tonsillitis.",2015 Jan 16,"['Arun Raj, G.R.', 'Shailaja, U.', 'Debnath, Parikshit', 'Banerjee, Subhadip', 'Rao, Prasanna N.']",J Tradit Complement Med,,,
,PMC,TARGETING THE eIF4F TRANSLATION INITIATION COMPLEX: A CRITICAL NEXUS FOR CANCER DEVELOPMENT,http://dx.doi.org/10.1158/0008-5472.CAN-14-2789,PMC4299928,,,"Elevated protein synthesis is an important feature of many cancer cells and often arises as a consequence of increased signaling flux channeled to eukaryotic initiation factor (eIF) 4F, the key regulator of the mRNA-ribosome recruitment phase of translation initiation. In many cellular and pre-clinical models of cancer, eIF4F deregulation results in changes in translational efficiency of specific mRNA classes. Importantly, many of these mRNAs code for proteins that potently regulate critical cellular processes such as cell growth and proliferation, enhanced cell survival, and cell migration that ultimately impinge on several hallmarks of cancer, including increased angiogenesis, deregulated growth control, enhanced cellular survival, epithelial-to-mesenchymal transition, invasion and metastasis. By being positioned as the molecular nexus downstream of key oncogenic signaling pathways (e.g. Ras, PI3K/AKT/TOR, and Myc), eIF4F serves as a direct link between important steps in cancer development and translation initiation. Identification of mRNAs particularly responsive to elevated eIF4F activity that typifies tumorigenesis underscores the critical role of eIF4F in cancer and raises the exciting possibility of developing new-in-class small molecules targeting translation initiation as anti-neoplastic agents.",,"['Pelletier, Jerry', 'Graff, Jeremy', 'Ruggero, Davide', 'Sonenberg, Nahum']",,,,
,PMC,Pressure‐controlled versus volume‐controlled ventilation for acute respiratory failure due to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS),http://dx.doi.org/10.1002/14651858.CD008807.pub2,PMC6457606,,,"BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) account for one‐quarter of cases of acute respiratory failure in intensive care units (ICUs). A third to half of patients will die in the ICU, in hospital or during follow‐up. Mechanical ventilation of people with ALI/ARDS allows time for the lungs to heal, but ventilation is invasive and can result in lung injury. It is uncertain whether ventilator‐related injury would be reduced if pressure delivered by the ventilator with each breath is controlled, or whether the volume of air delivered by each breath is limited. OBJECTIVES: To compare pressure‐controlled ventilation (PCV) versus volume‐controlled ventilation (VCV) in adults with ALI/ARDS to determine whether PCV reduces in‐hospital mortality and morbidity in intubated and ventilated adults. SEARCH METHODS: In October 2014, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Isssue 9), MEDLINE (1950 to 1 October 2014), EMBASE (1980 to 1 October 2014), the Latin American Caribbean Health Sciences Literature (LILACS) (1994 to 1 October 2014) and Science Citation Index‐Expanded (SCI‐EXPANDED) at the Institute for Scientific Information (ISI) Web of Science (1990 to 1 October 2014), as well as regional databases, clinical trials registries, conference proceedings and reference lists. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi‐RCTs (irrespective of language or publication status) of adults with a diagnosis of acute respiratory failure or acute on chronic respiratory failure and fulfilling the criteria for ALI/ARDS as defined by the American‐European Consensus Conference who were admitted to an ICU for invasive mechanical ventilation, comparing pressure‐controlled or pressure‐controlled inverse‐ratio ventilation, or an equivalent pressure‐controlled mode (PCV), versus volume‐controlled ventilation, or an equivalent volume‐controlled mode (VCV). DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected trials, assessed risk of bias and extracted data. We sought clarification from trial authors when needed. We pooled risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with their 95% confidence intervals (CIs) using a random‐effects model. We assessed overall evidence quality using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. MAIN RESULTS: We included three RCTs that randomly assigned a total of 1089 participants recruited from 43 ICUs in Australia, Canada, Saudi Arabia, Spain and the USA. Risk of bias of the included studies was low. Only data for mortality and barotrauma could be combined in the meta‐analysis. We downgraded the quality of evidence for the three mortality outcomes on the basis of serious imprecision around the effect estimates. For mortality in hospital, the RR with PCV compared with VCV was 0.83 (95% CI 0.67 to 1.02; three trials, 1089 participants; moderate‐quality evidence), and for mortality in the ICU, the RR with PCV compared with VCV was 0.84 (95% CI 0.71 to 0.99; two trials, 1062 participants; moderate‐quality evidence). One study provided no evidence of clear benefit with the ventilatory mode for mortality at 28 days (RR 0.88, 95% CI 0.73 to 1.06; 983 participants; moderate‐quality evidence). The difference in effect on barotrauma between PCV and VCV was uncertain as the result of imprecision and different co‐interventions used in the studies (RR 1.24, 95% CI 0.87 to 1.77; two trials, 1062 participants; low‐quality evidence). Data from one trial with 983 participants for the mean duration of ventilation, and from another trial with 78 participants for the mean number of extrapulmonary organ failures that developed with PCV or VCV, were skewed. None of the trials reported on infection during ventilation or quality of life after discharge. AUTHORS' CONCLUSIONS: Currently available data from RCTs are insufficient to confirm or refute whether pressure‐controlled or volume‐controlled ventilation offers any advantage for people with acute respiratory failure due to acute lung injury or acute respiratory distress syndrome. More studies including a larger number of people given PCV and VCV may provide reliable evidence on which more firm conclusions can be based.",,"['Chacko, Binila', 'Peter, John V', 'Tharyan, Prathap', 'John, George', 'Jeyaseelan, Lakshmanan']",,,,
,PMC,"The nsp1, nsp13, and M Proteins Contribute to the Hepatotropism of Murine Coronavirus JHM.WU",http://dx.doi.org/10.1128/JVI.03535-14,PMC4403414,,,"Mouse hepatitis virus (MHV) isolates JHM.WU and JHM.SD promote severe central nervous system disease. However, while JHM.WU replicates robustly and induces hepatitis, JHM.SD fails to replicate or induce pathology in the liver. These two JHM variants encode homologous proteins with few polymorphisms, and little is known about which viral proteins(s) is responsible for the liver tropism of JHM.WU. We constructed reverse genetic systems for JHM.SD and JHM.WU and, utilizing these full-length cDNA clones, constructed chimeric viruses and mapped the virulence factors involved in liver tropism. Exchanging the spike proteins of the two viruses neither increased replication of JHM.SD in the liver nor attenuated JHM.WU. By further mapping, we found that polymorphisms in JHM.WU structural protein M and nonstructural replicase proteins nsp1 and nsp13 are essential for liver pathogenesis. M protein and nsp13, the helicase, of JHM.WU are required for efficient replication in vitro and in the liver in vivo. The JHM.SD nsp1 protein contains a K194R substitution of Lys194, a residue conserved among all other MHV strains. The K194R polymorphism has no effect on in vitro replication but influences hepatotropism, and introduction of R194K into JHM.SD promotes replication in the liver. Conversely, a K194R substitution in nsp1 of JHM.WU or A59, another hepatotropic strain, significantly attenuates replication of each strain in the liver and increases IFN-β expression in macrophages in culture. Our data indicate that both structural and nonstructural proteins contribute to MHV liver pathogenesis and support previous reports that nsp1 is a Betacoronavirus virulence factor. IMPORTANCE The Betacoronavirus genus includes human pathogens, some of which cause severe respiratory disease. The spread of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) into human populations demonstrates the zoonotic potential of emerging coronaviruses, and there are currently no vaccines or effective antivirals for human coronaviruses. Thus, it is important to understand the virus-host interaction that regulates coronavirus pathogenesis. Murine coronavirus infection of mice provides a useful model for the study of coronavirus-host interactions, including the determinants of tropism and virulence. We found that very small changes in coronavirus proteins can profoundly affect tropism and virulence. Furthermore, the hepatotropism of MHV-JHM depends not on the spike protein and viral entry but rather on a combination of the structural protein M and nonstructural replicase-associated proteins nsp1 and nsp13, which are conserved among betacoronaviruses. Understanding virulence determinants will aid in the design of vaccines and antiviral strategies.",,"['Zhang, Rong', 'Li, Yize', 'Cowley, Timothy J.', 'Steinbrenner, Adam D.', 'Phillips, Judith M.', 'Yount, Boyd L.', 'Baric, Ralph S.', 'Weiss, Susan R.']",,,,
,PMC,Generation of a Transgenic Mouse Model of Middle East Respiratory Syndrome Coronavirus Infection and Disease,http://dx.doi.org/10.1128/JVI.03427-14,PMC4403411,,,"The emergence of Middle East respiratory syndrome-coronavirus (MERS-CoV) in the Middle East since 2012 has caused more than 900 human infections with ∼40% mortality to date. Animal models are needed for studying pathogenesis and for development of preventive and therapeutic agents against MERS-CoV infection. Nonhuman primates (rhesus macaques and marmosets) are expensive models of limited availability. Although a mouse lung infection model has been described using adenovirus vectors expressing human CD26/dipeptidyl peptidase 4 (DPP4), it is believed that a transgenic mouse model is needed for MERS-CoV research. We have developed this transgenic mouse model as indicated in this study. We show that transgenic mice globally expressing hCD26/DPP4 were fully permissive to MERS-CoV infection, resulting in relentless weight loss and death within days postinfection. High infectious virus titers were recovered primarily from the lungs and brains of mice at 2 and 4 days postinfection, respectively, whereas viral RNAs were also detected in the heart, spleen, and intestine, indicating a disseminating viral infection. Infected Tg(+) mice developed a progressive pneumonia, characterized by extensive inflammatory infiltration. In contrast, an inconsistent mild perivascular cuffing was the only pathological change associated with the infected brains. Moreover, infected Tg(+) mice were able to activate genes encoding for many antiviral and inflammatory mediators within the lungs and brains, coinciding with the high levels of viral replication. This new and unique transgenic mouse model will be useful for furthering knowledge of MERS pathogenesis and for the development of vaccine and treatments against MERS-CoV infection. IMPORTANCE Small and economical animal models are required for the controlled and extensive studies needed for elucidating pathogenesis and development of vaccines and antivirals against MERS. Mice are the most desirable small-animal species for this purpose because of availability and the existence of a thorough knowledge base, particularly of genetics and immunology. The standard small animals, mice, hamsters, and ferrets, all lack the functional MERS-CoV receptor and are not susceptible to infection. So, initial studies were done with nonhuman primates, expensive models of limited availability. A mouse lung infection model was described where a mouse adenovirus was used to transfect lung cells for receptor expression. Nevertheless, all generally agree that a transgenic mouse model expressing the DPP4 receptor is needed for MERS-CoV research. We have developed this transgenic mouse model as indicated in this study. This new and unique transgenic mouse model will be useful for furthering MERS research.",,"['Agrawal, Anurodh Shankar', 'Garron, Tania', 'Tao, Xinrong', 'Peng, Bi-Hung', 'Wakamiya, Maki', 'Chan, Teh-Sheng', 'Couch, Robert B.', 'Tseng, Chien-Te K.']",,,,
,PMC,Antigenic Relationships among Porcine Epidemic Diarrhea Virus and Transmissible Gastroenteritis Virus Strains,http://dx.doi.org/10.1128/JVI.03196-14,PMC4337547,,,"Porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) are economically important swine enteropathogenic coronaviruses. These two viruses belong to two distinct species of the Alphacoronavirus genus within Coronaviridae and induce similar clinical signs and pathological lesions in newborn piglets, but they are presumed to be antigenically distinct. In the present study, two-way antigenic cross-reactivity examinations between the prototype PEDV CV777 strain, three distinct U.S. PEDV strains (the original highly virulent PC22A, S indel Iowa106, and S 197del PC177), and two representative U.S. TGEV strains (Miller and Purdue) were conducted by cell culture immunofluorescent (CCIF) and viral neutralization (VN) assays. None of the pig TGEV antisera neutralized PEDV and vice versa. One-way cross-reactions were observed by CCIF between TGEV Miller hyperimmune pig antisera and all PEDV strains. Enzyme-linked immunosorbent assays, immunoblotting using monoclonal antibodies and Escherichia coli-expressed recombinant PEDV and TGEV nucleocapsid (N) proteins, and sequence analysis suggested at least one epitope on the N-terminal region of PEDV/TGEV N protein that contributed to this cross-reactivity. Biologically, PEDV strain CV777 induced greater cell fusion in Vero cells than did U.S. PEDV strains. Consistent with the reported genetic differences, the results of CCIF and VN assays also revealed higher antigenic variation between PEDV CV777 and U.S. strains. IMPORTANCE Evidence of antigenic cross-reactivity between porcine enteric coronaviruses, PEDV and TGEV, in CCIF assays supports the idea that these two species are evolutionarily related, but they are distinct species defined by VN assays. Identification of PEDV- or TGEV-specific antigenic regions allows the development of more specific immunoassays for each virus. Antigenic and biologic variations between the prototype and current PEDV strains could explain, at least partially, the recurrence of PEDV epidemics. Information on the conserved antigenicity among PEDV strains is important for the development of PEDV vaccines to protect swine from current highly virulent PEDV infections.",,"['Lin, Chun-Ming', 'Gao, Xiang', 'Oka, Tomoichiro', 'Vlasova, Anastasia N', 'Esseili, Malak A.', 'Wang, Qiuhong', 'Saif, Linda J.']",,,,
,PMC,Inactivation of Murine Norovirus on a Range of Copper Alloy Surfaces Is Accompanied by Loss of Capsid Integrity,http://dx.doi.org/10.1128/AEM.03280-14,PMC4292492,,,"Norovirus is one of the most common causes of acute viral gastroenteritis. The virus is spread via the fecal-oral route, most commonly from infected food and water, but several outbreaks have originated from contamination of surfaces with infectious virus. In this study, a close surrogate of human norovirus causing gastrointestinal disease in mice, murine norovirus type 1 (MNV-1), retained infectivity for more than 2 weeks following contact with a range of surface materials, including Teflon (polytetrafluoroethylene [PTFE]), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. Persistence was slightly prolonged on ceramic surfaces. A previous study in our laboratory observed that dry copper and copper alloy surfaces rapidly inactivated MNV-1 and destroyed the viral genome. In this new study, we have observed that a relatively small change in the percentage of copper, between 70 and 80% in copper nickels and 60 and 70% in brasses, had a significant influence on the ability of the alloy to inactivate norovirus. Nickel alone did not affect virus, but zinc did have some antiviral effect, which was synergistic with copper and resulted in an increased efficacy of brasses with lower percentages of copper. Electron microscopy of purified MNV-1 that had been exposed to copper and stainless steel surfaces suggested that a massive breakdown of the viral capsid had occurred on copper. In addition, MNV-1 that had been exposed to copper and treated with RNase demonstrated a reduction in viral gene copy number. This suggests that capsid integrity is compromised upon contact with copper, allowing copper ion access to the viral genome.",,"['Warnes, Sarah L.', 'Summersgill, Emma N.', 'Keevil, C. William']",,,,
,PMC,MS2 Virus Inactivation by Atmospheric-Pressure Cold Plasma Using Different Gas Carriers and Power Levels,http://dx.doi.org/10.1128/AEM.03322-14,PMC4292470,,,"In this study, airborne MS2 bacteriophages were exposed for subsecond time intervals to atmospheric-pressure cold plasma (APCP) produced using different power levels (20, 24, and 28 W) and gas carriers (ambient air, Ar-O(2) [2%, vol/vol], and He-O(2) [2%, vol/vol]). In addition, waterborne MS2 viruses were directly subjected to the APCP treatment for up to 3 min. MS2 viruses with and without the APCP exposure were examined by scanning electron microscopy (SEM), reverse transcription-PCR (RT-PCR), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Viral inactivation was shown to exhibit linear relationships with the APCP generation power and exposure time (R(2) > 0.95 for all energy levels tested) up to 95% inactivation (1.3-log reduction) after a subsecond airborne exposure at 28 W; about the same inactivation level was achieved for waterborne viruses with an exposure time of less than 1 min. A larger amount of reactive oxygen species (ROS), such as atomic oxygen, in APCP was detected for a higher generation power with Ar-O(2) and He-O(2) gas carriers. SEM images, SDS-PAGE, and agarose gel analysis of exposed waterborne viruses showed various levels of damage to both surface proteins and their related RNA genes after the APCP exposure, thus leading to the loss of their viability and infectivity.",,"['Wu, Yan', 'Liang, Yongdong', 'Wei, Kai', 'Li, Wei', 'Yao, Maosheng', 'Zhang, Jue', 'Grinshpun, Sergey A.']",,,,
,PMC,Mitochondrial Dynamics and Viral infections: a close nexus,http://dx.doi.org/10.1016/j.bbamcr.2014.12.040,PMC4500740,,,"Viruses manipulate cellular machinery and functions to subvert intracellular environment conducive for viral proliferation. They strategically alter functions of the multitasking mitochondria to influence energy production, metabolism, survival, and immune signaling. Mitochondria either occur as heterogeneous population of individual organelles or large interconnected tubular network. The mitochondrial network is highly susceptible to physiological and environmental insults, including viral infections, and is dynamically maintained by mitochondrial fission and fusion. Mitochondrial dynamics in tandem with mitochondria-selective autophagy ‘mitophagy’ coordinates mitochondrial quality control and homeostasis. Mitochondrial dynamics impacts cellular homeostasis, metabolism, and innate-immune signaling, and thus is a major determinant of the outcome of viral infections. Hepatitis B and C viruses exploit mitochondrial dynamics to ensure cell survival and escape from innate immunity, thereby promoting persistent/chronic viral infection. Herein, we review how mitochondrial dynamics is affected during viral infections and how this complex interplay benefits the viral infectious process and associated diseases.",,"['Khan, Mohsin', 'Syed, Gulam Hussain', 'Kim, Seong-Jun', 'Siddiqui, Aleem']",,,,
,PMC,"Epidemiologic, clinical, and virologic characteristics of human rhinovirus infection among otherwise healthy children and adults",http://dx.doi.org/10.1016/j.jcv.2015.01.007,PMC4347877,,,"BACKGROUND: Human rhinovirus (HRV) is a major cause of influenza-like illness (ILI) in adults and children. Differences in disease severity by HRV species have been described among hospitalized patients with underlying illness. Less is known about the clinical and virologic characteristics of HRV infection among otherwise healthy populations, particularly adults. OBJECTIVES: To characterize molecular epidemiology of HRV and association between HRV species and clinical presentation and viral shedding. STUDY DESIGN: Observational, prospective, facility-based study of ILI was conducted from February 2010 to April 2012. Collection of nasopharyngeal specimens, patient symptoms, and clinical information occurred on days 0, 3, 7, and 28. Patients recorded symptom severity daily for the first 7 days of illness in a symptom diary. HRV was identified by RT-PCR and genotyped for species determination. Cases who were co-infected with other viral respiratory pathogens were excluded from the analysis. We evaluated the associations between HRV species, clinical severity, and patterns of viral shedding. RESULTS: Eighty-four HRV cases were identified and their isolates genotyped. Of these, 62 (74%) were >18y. Fifty-four were HRV-A, 11 HRV-B, and 19 HRV-C. HRV-C infection was more common among children than adults (59% vs. 10%, P<0.001). Among adults, HRV-A was associated with higher severity of upper respiratory symptoms compared to HRV-B (P=0.02), but no such association was found in children. In addition, adults shed HRV-A significantly longer than HRV-C (Ptrend=0.01). CONCLUSIONS: Among otherwise healthy adults with HRV infection, we observed species-specific differences in respiratory symptom severity and duration of viral shedding.",,"['Chen, Wei-Ju', 'Arnold, John C.', 'Fairchok, Mary P.', 'Danaher, Patrick J.', 'McDonough, Erin A.', 'Blair, Patrick J.', 'Garcia, Josefina', 'Halsey, Eric S.', 'Schofield, Christina', 'Ottolini, Martin', 'Mor, Deepika', 'Ridoré, Michelande', 'Burgess, Timothy H.', 'Millar, Eugene V.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.03515-14,PMC4300771,,,,,,,,,
,PMC,Correlation between Diarrhea Severity and Oocyst Count via Quantitative PCR or Fluorescence Microscopy in Experimental Cryptosporidiosis in Calves,http://dx.doi.org/10.4269/ajtmh.14-0488,PMC4347389,,,"Cryptosporidium is an important diarrhea-associated pathogen, however the correlation between parasite burden and diarrhea severity remains unclear. We studied this relationship in 10 experimentally infected calves using immunofluorescence microscopy and real-time polymerase chain reaction (qPCR) (N = 124 fecal samples). The qPCR data were corrected for extraction/amplification efficiency and gene copy number to generate parasite counts. The qPCR and microscopic oocyst quantities exhibited significant correlation (R(2) = 0.33, P < 0.05), however qPCR had increased sensitivity. Upon comparison with diarrhea severity scores (from 0 to 3), a PCR-based count of ≥ 2.6 × 10(5) parasites or an immunofluorescence microscopy count of ≥ 4.5 × 10(4) oocysts were discriminatory predictors of moderate-to-severe diarrhea (versus no-to-mild diarrhea), with accuracies and predictive values of 72–82%. In summary, a quantitative approach for Cryptosporidium can refine predictive power for diarrhea and appears useful for distinguishing clinical cryptosporidiosis versus subclinical infection.",,"['Operario, Darwin J.', 'Bristol, Lauren S.', 'Liotta, Janice', 'Nydam, Daryl V.', 'Houpt, Eric R.']",,,,
,PMC,Ecological dynamics of emerging bat virus spillover,http://dx.doi.org/10.1098/rspb.2014.2124,PMC4262174,,,"Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility.",,"['Plowright, Raina K.', 'Eby, Peggy', 'Hudson, Peter J.', 'Smith, Ina L.', 'Westcott, David', 'Bryden, Wayne L.', 'Middleton, Deborah', 'Reid, Peter A.', 'McFarlane, Rosemary A.', 'Martin, Gerardo', 'Tabor, Gary M.', 'Skerratt, Lee F.', 'Anderson, Dale L.', 'Crameri, Gary', 'Quammen, David', 'Jordan, David', 'Freeman, Paul', 'Wang, Lin-Fa', 'Epstein, Jonathan H.', 'Marsh, Glenn A.', 'Kung, Nina Y.', 'McCallum, Hamish']",,,,
,PMC,Beyond receptors and signaling: epigenetic factors in the regulation of innate immunity,http://dx.doi.org/10.1038/icb.2014.101,PMC4885213,,,"The interaction of innate immune cells with pathogens leads to changes in gene expression that elicit our body’s first line of defense against infection. Although signaling pathways and transcription factors have a central role, it is becoming increasingly clear that epigenetic factors, in the form of DNA or histone modifications, as well as noncoding RNAs, are critical for generating the necessary cell lineage as well as context-specific gene expression in diverse innate immune cell types. Much of the epigenetic landscape is set during cellular differentiation; however, pathogens and other environmental triggers also induce changes in histone modifications that can either promote tolerance or ‘train’ innate immune cells for a more robust antigen-independent secondary response. Here we review the important contribution of epigenetic factors to the initiation, maintenance and training of innate immune responses. In addition, we explore how pathogens have hijacked these mechanisms for their benefit and the potential of small molecules targeting chromatin machinery as a way to boost or subdue the innate immune response in disease.",,"['Mehta, Stuti', 'Jeffrey, Kate L']",,,,
,PMC,"Picornavirus RNA polyadenylation by 3D(pol), the viral RNA-dependent RNA polymerase",http://dx.doi.org/10.1016/j.virusres.2014.12.030,PMC4801031,,,"Poly(A) tails are functionally important features of all picornavirus RNA genomes. Some viruses have genomes with relatively short poly(A) tails (encephalomyocarditis virus) whereas others have genomes with longer poly(A) tails (polioviruses and rhinoviruses). Here we review the polyadenylation of picornavirus RNA as it relates to the structure and function of 3D(pol). Poliovirus 3D(pol) uses template-dependent reiterative transcription mechanisms as it replicates the poly(A) tails of viral RNA (Steil et al., 2010). These mechanisms are analogous to those involved in the polyadenylation of vesicular stomatitis virus and influenza virus mRNAs. 3D(pol) residues intimately associated with viral RNA templates and products regulate the size of poly(A) tails in viral RNA (Kempf et al., 2013). Consistent with their ancient evolutionary origins, picornavirus 3D(pol) and telomerase reverse transcriptase (TERT) share structural and functional features. Structurally, both 3D(pol) and TERT assume a “right-hand” conformation with thumb, palm and fingers domains encircling templates and products. Functionally, both 3D(pol) and TERT use template-dependent reiterative transcription mechanisms to synthesize repetitive sequences: poly(A) tails in the case of picornavirus RNA genomes and DNA telomeres in the case of eukaryotic chromosomes. Thus, picornaviruses and their eukaryotic hosts (humans & animals) maintain the 3’ ends of their respective genomes via evolutionarily related mechanisms.",,"['Kempf, Brian J', 'Barton, David J.']",,,,
,PMC,Health promotion interventions and policies addressing excessive alcohol use: A systematic review of national and global evidence as a guide to health-care reform in China,http://dx.doi.org/10.1111/add.12784,PMC4350681,,,"AIMS: Steady increases in alcohol consumption and related problems are likely to accompany China's rapid epidemiologic transition and profit-based marketing activities. We reviewed research on health promotion interventions and policies to address excessive drinking and to guide health-care reform. METHODS: We searched in Chinese and English language databases and included 21 studies in China published between 1980 and 2013 that covered each policy area from the WHO Global Strategy to Reduce the Harmful Use of Alcohol. We evaluated and compared preventive interventions to the global alcohol literature for cross-national applicability. RESULTS: In contrast with hundreds of studies in the global literature, 11 of 12 studies from mainland China were published in Chinese; six of ten in English were on taxation from Taiwan or Hong Kong. Most studies demonstrated effectiveness in reducing excessive drinking, and some reported the reduction of health problems. Seven were randomized controlled trials. Studies targeted schools, drink-driving, workplaces, the health sector, and taxation. CONCLUSIONS: China is the world's largest alcohol market, yet there has been little growth in alcohol policy research related to health promotion interventions over the past decade. Guided by a public health approach, the WHO Global Strategy, and health reform experience in Russia, Australia, Mexico, and the USA, China could improve its public health response through better coordination and implementation of surveillance and evidence-based research, and through programmatic and legal responses such as public health law research, screening and early intervention within health systems, and the implementation of effective alcohol control strategies.",,"['Li, Qing', 'Babor, Thomas F.', 'Zeigler, Donald', 'Xuan, Ziming', 'Morisky, Donald', 'Hovell, Melbourne F.', 'Nelson, Toben F.', 'Shen, Weixing', 'Li, Bing']",,,,
,PMC,The Moral Challenge of Ebola,http://dx.doi.org/10.2105/AJPH.2014.302413,PMC4265927,,,,,"Rothstein, Mark A.",,,,
,PMC,Legal Authority for Infectious Disease Reporting in the United States: Case Study of the 2009 H1N1 Influenza Pandemic,http://dx.doi.org/10.2105/AJPH.2014.302192,PMC4265911,,,"Tracking of infectious diseases is a public health core function essential to disease prevention and control. Each state mandates reporting of certain infectious diseases to public health authorities. These laws vary by state, and the variation could affect the ability to collect critical information. The 2009 H1N1 influenza pandemic served as a case study to examine the legal authority in the 50 states; Washington, DC; and New York City for mandatory infectious disease reporting, particularly for influenza and new or emerging infectious diseases. Our study showed reporting laws to be generally present and functioning well; nevertheless, jurisdictions should be mindful of their mandated parameters and review the robustness of their laws before they face a new or emerging disease outbreak.",,"['Danila, Richard N.', 'Laine, Ellen S.', 'Livingston, Franci', 'Como-Sabetti, Kathryn', 'Lamers, Lauren', 'Johnson, Kelli', 'Barry, Anne M.']",,,,
,PMC,Genetic variation analyses of porcine epidemic diarrhea virus isolated in mid-eastern China from 2011 to 2013,,PMC4283240,,,"Porcine diarrhea outbreaks caused by porcine epidemic diarrhea virus (PEDV) has occurred in China with significant losses of piglets since 2010. In this study, the complete S and ORF3 genes of 15 field PEDV isolates in mid-eastern China from 2011 to 2013 were detected and compared with other reference strains. Based on S gene, all of the PEDV strains could be assigned to 3 genogroups. Only 1 isolate, JS120103, belonged to genogroup 1 and showed a close relationship with previous Chinese strains DX and JS-2004-2, European strain CV777, and Korean strain DR13. The other 14 isolates belonged to genogroup 3 and showed a close relationship with other Chinese strains isolated after 2010. The S genes of those isolates were 9 nucleotides longer in length than JS120103 and the other reference strains in genogroup 1, with 15 bp insertion and 6 bp deletion. Homology analyses revealed that all of the Chinese field isolates, except JS120103, are 97.6% to 100% (95.8% to 100%) identical in nucleotide (deduced amino acid) sequence to each other. Meanwhile, based on the ORF3 gene, all of the PEDV isolates could be separated into 3 genogroups. Eleven of the 15 field isolates in this study belonged to genogroup 3 and were 95.8% to 100% identical in nucleotide sequence or 95.6% to 100% in deduced amino acid sequence to each other. Our results indicate that the variant PEDV strain spread wildly in mid-eastern China. This will be useful to take into consideration in the control and prevention of this disease.",,"['Zhao, Pan-deng', 'Tan, Chen', 'Dong, Yanpen', 'Li, Yufeng', 'Shi, Xiaoli', 'Bai, Juan', 'Jiang, Ping']",,,,
,PMC,Exposure of feral swine (Sus scrofa) in the United States to selected pathogens,,PMC4283238,,,"Feral swine (Sus scrofa) are widely distributed in the United States. In 2011 and 2012, serum samples and tonsils were recovered from 162 and 37 feral swine, respectively, in the US to evaluate exposure to important swine endemic pathogens. Antibodies against porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) were found in 2.5% and 25.3% of tested sera, respectively. Positive serological reactions against Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae have been detected in 19.7% and 69.7% of animals. More than 15% of animals presented antibodies against these 2 pathogens simultaneously. Most animals were also seropositive for Lawsonia intracellularis. Feral swine can also be involved in transmission of zoonotic agents. Almost 50% of animals possessed antibodies against Salmonella. In addition, 94.4% of animals were carriers of Streptococcus suis in their tonsils. In conclusion, feral swine may be considered as a potential reservoir for different endemic diseases in domestic pigs, as well as for important zoonotic agents.",,"['Baroch, John A.', 'Gagnon, Carl A.', 'Lacouture, Sonia', 'Gottschalk, Marcelo']",,,,
,PMC,Prolonged survival of a cat diagnosed with feline infectious peritonitis by immunohistochemistry,,PMC4266056,,,"A 4-year-old, neutered male, British shorthair cat was presented with inappetence, vomiting, hyperproteinemia, and hyperglobulinemia. An exploratory celiotomy identified enlarged mesenteric lymph nodes. Immunohistochemistry of lymph node biopsies confirmed feline infectious peritonitis. This patient had a prolonged survival of 787 d after initial presentation.",,"['Hugo, Timothy B.', 'Heading, Kathryn L.']",,,,
,PMC,Optic Neuritis: A Model for the Immuno-pathogenesis of Central Nervous System Inflammatory Demyelinating Diseases,http://dx.doi.org/10.2174/1573395511666150707181644,PMC5791743,,,"Evidence for the tenuous regulation between the immune system and central nervous system (CNS) can be found with examples of interaction between these organ systems gone awry. Multiple sclerosis (MS) is the prototypical inflammatory disease of the CNS and is characterized by widely distributed inflammatory demyelinating plaques that can involve the brain, spinal cord and/or optic nerves. Optic neuritis (ON), inflammatory injury of the optic nerve that frequently occurs in patients with MS, has been the focus of intense study in part given the readily accessible nature of clinical outcome measures. Exploring the clinical and pathological features of ON in relation to other inflammatory demyelinating conditions of the CNS, namely MS and neuromyelitis optica, provides an opportunity to glean common and distinct mechanisms of disease. Emerging data from clinical studies along with various animal models involving ON implicate innate and adaptive immune responses directed at glial targets, including myelin oligodendrocyte glycoprotein and aquaporin 4. Resolution of inflammation in ON is commonly observed both clinically and experimentally, but persistent nerve injury is also one emerging hallmark of ON. One hypothesis seeking evaluation is that, in comparison to other sites targeted in MS, the optic nerve is a highly specialized target within the CNS predisposing to unique immunologic processes that generate ON. Overall, ON serves as a highly relevant entity for understanding the pathogenesis of other CNS demyelinating conditions, most notably MS.",,"['Wu, Gregory F.', 'Parker Harp, Chelsea R.', 'Shindler, Kenneth S.']",,,,
,PMC,Macrophages and the Viral Dissemination Super Highway,,PMC4774560,,,"Monocytes and macrophages are key components of the innate immune system yet they are often the victims of attack by infectious agents. This review examines the significance of viral infection of macrophages. The central hypothesis is that macrophage tropism enhances viral dissemination and persistence, but these changes may come at the cost of reduced replication in cells other than macrophages.",,"['Klepper, Arielle', 'Branch, Andrea D']",,,,
,PMC,Role of licochalcone A on thymic stromal lymphopoietin expression: Implications for asthma,http://dx.doi.org/10.1177/1535370214545020,PMC4935181,,,"Asthma is a common chronic inflammatory disease characterized by the infiltration and accumulation of memory-like Th2 cells and eosinophils. Viral infection has emerged as the most common cause of severe episodes of asthma. For the treatment of bronchial asthma, the root of liquorice (Glycyrrhiza glabra) has been used as a traditional medicine in the East and West. Licochalcone A is the predominant, characteristic chalcone in liquorice root. To determine whether licochalcone A possesses an anti-inflammatory effect, we tested its effect on the expression and production of thymic stromal lymphopoietin (TSLP) in BEAS 2B cells and primary bronchial epithelial cells. We found that polyinosinic-polycytidylic acid (poly-IC)-induced TSLP expression was suppressed by treatment with licochalcone A in a dose- and time-dependent manner. We also found that poly-IC-induced mRNA expression of other proinflammatory mediators such as MCP-1, RANTES, and IL-8 was suppressed by licochalcone A. Furthermore, licochalcone A suppressed poly-IC-induced nuclear factor kappa B (NF-κB) nuclear translocation and DNA-binding activity by suppressing the Iκβ kinase (IKK) activity but not by direct phosphorylation of p65 at serine 276. Collectively, our findings suggest that licochalcone A suppresses poly-IC-induced TSLP expression and production by inhibiting the IKK/NF-κB signaling pathway, which might be involved in the pathogenesis of virus-exacerbated asthma. Further elucidation of the mechanisms underlying these observations can help develop therapeutic strategies for virally induced asthma.",,"['Kim, Sung-Ho', 'Yang, Min', 'Xu, Jian-Gang', 'Yu, Xi', 'Qian, Xue-Jiao']",,,,
,PMC,Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice,http://dx.doi.org/10.1177/1535370214546273,PMC4446989,,,"The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD-scid IL2rγ(null) mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT-NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines.",,"['Jaiswal, Smita', 'Smith, Kenneth', 'Ramirez, Alejandro', 'Woda, Marcia', 'Pazoles, Pamela', 'Shultz, Leonard D', 'Greiner, Dale L', 'Brehm, Michael A', 'Mathew, Anuja']",,,,
,PMC,Refining the approach to vaccines against influenza A viruses with pandemic potential,http://dx.doi.org/10.2217/fvl.15.69,PMC4648374,,,"Vaccination is the most effective strategy for prevention and control of influenza. Timely production and deployment of seasonal influenza vaccines is based on an understanding of the epidemiology of influenza and on global disease and virologic surveillance. Experience with seasonal influenza vaccines guided the initial development of pandemic influenza vaccines. A large investment in pandemic influenza vaccines in the last decade has resulted in much progress and a body of information that can now be applied to refine the established paradigm. Critical and complementary considerations for pandemic influenza vaccines include improved assessment of the pandemic potential of animal influenza viruses, proactive development and deployment of pandemic influenza vaccines, and application of novel platforms and strategies for vaccine production and administration.",,"['Czako, Rita', 'Subbarao, Kanta']",,,,
,PMC,Assessing Community Reactions to Ebola Virus Disease and Other Disasters: Using Social Psychological Research to Enhance Public Health and Disaster Communications,http://dx.doi.org/10.4172/1522-4821.1000147,PMC4382086,,,"Drawing on the lessons learned from previous disaster and disease outbreak studies over the past two decades, in the following article we review research related to social psychological assessment of community attitudes, knowledge, and beliefs associated with the recent Ebola outbreak and other public health threats, and discuss the use of this information to assist in future disaster planning and crisis communications. Psychologists, physicians, and others in the healthcare field need to be aware of these developments and involved with preparations related to mitigating the psychological impact of Ebola disease outbreaks among different populations, as well as other potential public health threats in the future.",,"['Boscarino, Joseph A.', 'Adams, Richard E.']",,,,
,PMC,"Breeding, Husbandry, Veterinary Care, and Hematology of Marsh Rice Rats (Oryzomys palustris), a Small Animal Model for Periodontitis",,PMC4311742,,,"Rice rats (Oryzomys palustris) are a recognized animal model for studying periodontal disease and the photoperiodic regulation of reproduction. Here we share information regarding the breeding, husbandry, veterinary care, and hematologic findings about this animal species to facilitate its use in studies at other research institutions. Rice rats initially were quarantined and monitored for excluded pathogens by using microbiologic, parasitologic, and serologic methods with adult female Mus musculus and Rattus norvegicus sentinel animals. Breeders were paired in a monogamous, continuous-breeding system. Rats were housed in static filter-top cages, maintained on commercial chow under 14:10-h light:dark cycles at 68 to 79 °F (20.0 to 26.1 °C) and 30% to 70% humidity. Rice rats apparently adapt relatively well to standard laboratory conditions, despite their aggressive behavior toward conspecifics and humans. Our analysis of 97 litters revealed that dams gave birth to an average of 5.2 pups per dam and weaned 4.2 pups per dam. Several procedures and biologic reagents normally used in standard laboratory rodents (mice and rats) can be used with rice rats. In addition, we present hematologic and serum chemistry values that can be used as preliminary reference values for future studies involving rice rats.",,"['Aguirre, J Ignacio', 'Edmonds, Kent', 'Zamora, Bernadette', 'Pingel, Jennifer', 'Thomas, Linda', 'Cancel, Denisse', 'Schneider, Laura', 'Reinhard, Mary K', 'Battles, August H', 'Akhter, Mohammed P', 'Kimmel, Donald B', 'Wronski, Thomas J']",,,,
,PMC,Reduction of Myeloid-derived Suppressor Cells and Lymphoma Growth by a Natural Triterpenoid,http://dx.doi.org/10.1002/jcb.24946,PMC5012903,,,"Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A’s anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen presentation and CD4+ T cell recognition of lymphoma in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma.",,"['Radwan, Faisal F. Y.', 'Hossain, Azim', 'God, Jason M.', 'Leaphart, Nathan', 'Elvington, Michelle', 'Nagarkatti, Mitzi', 'Tomlinson, Stephen', 'Haque, Azizul']",,,,
,PMC,Fit Assessment of N95 Filtering-Facepiece Respirators in the U.S. Centers for Disease Control and Prevention Strategic National Stockpile,,PMC4752193,,,"National Institute for Occupational Safety and Health (NIOSH)-approved N95 filtering-facepiece respirators (FFR) are currently stockpiled by the U.S. Centers for Disease Control and Prevention (CDC) for emergency deployment to healthcare facilities in the event of a widespread emergency such as an influenza pandemic. This study assessed the fit of N95 FFRs purchased for the CDC Strategic National Stockpile. The study addresses the question of whether the fit achieved by specific respirator sizes relates to facial size categories as defined by two NIOSH fit test panels. Fit test data were analyzed from 229 test subjects who performed a nine-donning fit test on seven N95 FFR models using a quantitative fit test protocol. An initial respirator model selection process was used to determine if the subject could achieve an adequate fit on a particular model; subjects then tested the adequately fitting model for the nine-donning fit test. Only data for models which provided an adequate initial fit (through the model selection process) for a subject were analyzed for this study. For the nine-donning fit test, six of the seven respirator models accommodated the fit of subjects (as indicated by geometric mean fit factor > 100) for not only the intended NIOSH bivariate and PCA panel sizes corresponding to the respirator size, but also for other panel sizes which were tested for each model. The model which showed poor performance may not be accurately represented because only two subjects passed the initial selection criteria to use this model. Findings are supportive of the current selection of facial dimensions for the new NIOSH panels. The various FFR models selected for the CDC Strategic National Stockpile provide a range of sizing options to fit a variety of facial sizes.",,"['Bergman, Michael', 'Zhuang, Ziqing', 'Brochu, Elizabeth', 'Palmiero, Andrew']",,,,
,PMC,RSV and its propensity for causing bronchiolitis,http://dx.doi.org/10.1002/path.4462,PMC5638117,,,"Infants and young children with acute onset of wheezing and reduced respiratory airflows are often diagnosed with obstruction and inflammation of the small bronchiolar airways, i.e., bronchiolitis. The most common eitological agents causing bronchiolitis in young children are the respiratory viruses and of the commonly encountered respiratory viruses, Respiratory Syncytial Virus (RSV) has a propensity for causing bronchiolitis. Indeed, RSV bronchiolitis remains the major reason why previously healthy infants are admitted to hospital. Why RSV infection is such a predominant cause of bronchiolitis is the subject of this review. By reviewing the available histopathology of RSV bronchiolitis both in humans and relevant animal models we identify hallmark features of RSV infection of the distal airways and focus attention on the consequences of columnar cell cytopathology occurring in the bronchioles, which directly impacts the development of bronchiolar obstruction, inflammation and disease.",,"['Pickles, Raymond J', 'DeVincenzo, John']",,,,
,PMC,Against Ebola: type I interferon guard risk and mesenchymal stromal cell combat sepsis,http://dx.doi.org/10.1631/jzus.B1400365,PMC4288939,,,,,"['Zhang, Lei', 'Wang, Hao', 'Zhang, Yi-qing']",,,,
,PMC,Identification of SUMO E3 Ligase-Specific Substrates Using the HuProt Human Proteome Microarray,http://dx.doi.org/10.1007/978-1-4939-2550-6_32,PMC5882486,,,"The functional protein microarray is a powerful and versatile systems biology and proteomics tool that allows the rapid activity profiling of thousands of proteins in parallel. We have recently developed a human proteome array, the HuProt array, which includes ~80 % of all the full-length proteins of the human proteome. In one recent application of the HuProt array, we identified numerous SUMO E3 ligase-dependent SUMOylation substrates. For many SUMO E3 ligases, only a small number of substrates have been identified and the target specificities of these ligases therefore remain poorly defined. In this protocol, we outline a method we developed using the HuProt array to screen the human proteome to identify novel SUMO E3 ligase substrates recognized by specific E3 ligases.",,"['Cox, Eric', 'Uzoma, Ijeoma', 'Guzzo, Catherine', 'Jeong, Jun Seop', 'Matunis, Michael', 'Blackshaw, Seth', 'Zhu, Heng']",,,,
,PMC,Engineering Infectious cDNAs of Coronavirus as Bacterial Artificial Chromosomes,http://dx.doi.org/10.1007/978-1-4939-2438-7_13,PMC4726977,,,"The large size of the coronavirus (CoV) genome (around 30 kb) and the instability in bacteria of plasmids carrying CoV replicase sequences, represent serious restrictions for the development of CoV infectious clones using reverse genetic systems similar to those used for smaller positive sense RNA viruses. To overcome these problems, several approaches have been established in the last thirteen years. Here we describe the engineering of CoV full-length cDNA clones as bacterial artificial chromosomes (BACs), using the Middle East respiratory syndrome CoV (MERS-CoV) as a model.",,"['Almazán, Fernando', 'Márquez-Jurado, Silvia', 'Nogales, Aitor', 'Enjuanes, Luis']",,,,
,PMC,Coronaviruses: An Overview of Their Replication and Pathogenesis,http://dx.doi.org/10.1007/978-1-4939-2438-7_1,PMC4369385,,,"Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, an unusually large RNA genome, and a unique replication strategy. Coronaviruses cause a variety of diseases in mammals and birds ranging from enteritis in cows and pigs and upper respiratory disease chickens to potentially lethal human respiratory infections. Here we provide a brief introduction to coronaviruses discussing their replication and pathogenicity, and current prevention and treatment strategies. We will also discuss the outbreaks of the highly pathogenic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the recently identified Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV).",,"['Fehr, Anthony R.', 'Perlman, Stanley']",,,,
,PMC,New Digital Technologies for the Surveillance of Infectious Diseases at Mass Gathering Events,http://dx.doi.org/10.1016/j.cmi.2014.12.017,PMC4332877,,,"Outbreaks of infectious diseases at mass gatherings can strain the health system of the host region and pose a threat to local and global health. In addition to strengthening existing surveillance systems, most host nations also utilize novel technologies to assess disease risk and augment traditional surveillance approaches. We review novel approaches to disease surveillance utilizing the Internet, mobile phone applications, and wireless sensor networks. These novel approaches to disease surveillance can result in prompt detection.",,"['Nsoesie, Elaine O.', 'Kluberg, Sheryl A.', 'Mekaru, Sumiko R.', 'Majumder, Maimuna S.', 'Khan, Kamran', 'Hay, Simon I.', 'Brownstein, John S.']",,,,
,PMC,Human Cytomegalovirus Exploits Interferon-Induced Transmembrane Proteins To Facilitate Morphogenesis of the Virion Assembly Compartment,http://dx.doi.org/10.1128/JVI.03416-14,PMC4337551,,,"Recently, interferon-induced transmembrane proteins (IFITMs) have been identified to be key effector molecules in the host type I interferon defense system. The invasion of host cells by a large range of RNA viruses is inhibited by IFITMs during the entry step. However, the roles of IFITMs in DNA virus infections have not been studied in detail. In this study, we report that human cytomegalovirus (HCMV), a large human DNA virus, exploits IFITMs to facilitate the formation of the virion assembly compartment (vAC) during infection of human fibroblasts. We found that IFITMs were expressed constitutively in human embryonic lung fibroblasts (MRC5 cells). HCMV infection inhibited IFITM protein accumulation in the later stages of infection. Overexpression of an IFITM protein in MRC5 cells slightly enhanced HCMV production and knockdown of IFITMs by RNA interference reduced the virus titer by about 100-fold on day 8 postinfection, according to the findings of a virus yield assay at a low multiplicity of infection. Virus gene expression and DNA synthesis were not affected, but the typical round structure of the vAC was not formed after the suppression of IFITMs, thereby resulting in defective virion assembly and the production of less infectious virion particles. Interestingly, the replication of herpes simplex virus, a human herpesvirus that is closely related to HCMV, was not affected by the suppression of IFITMs in MRC5 cells. These results indicate that IFITMs are involved in a specific pathway required for HCMV replication. IMPORTANCE HCMV is known to repurpose the interferon-stimulated genes (ISGs) viperin and tetherin to facilitate its replication. Our results expand the range of ISGs that can be exploited by HCMV for its replication. This is also the first report of a proviral function of IFITMs in DNA virus replication. In addition, whereas previous studies showed that IFITMs modulate virus entry, which is a very early stage in the virus life cycle, we identified a new function of IFITMs during the very late stage of virus replication, i.e., virion assembly. Virus entry and assembly both involve vesicle transport and membrane fusion; thus, a common biochemical activity of IFITMs is likely to be involved. Therefore, our findings may provide a new platform for dissecting the molecular mechanism of action of IFITMs during the blocking or enhancement of virus infection, which are under intense investigation in this field.",,"['Xie, Maorong', 'Xuan, Baoqin', 'Shan, Jiaoyu', 'Pan, Deng', 'Sun, Yamei', 'Shan, Zhao', 'Zhang, Jinping', 'Yu, Dong', 'Li, Bin', 'Qian, Zhikang']",,,,
,PMC,"Discovery of a Novel Coronavirus, China Rattus Coronavirus HKU24, from Norway Rats Supports the Murine Origin of Betacoronavirus 1 and Has Implications for the Ancestor of Betacoronavirus Lineage A",http://dx.doi.org/10.1128/JVI.02420-14,PMC4337523,,,"We discovered a novel Betacoronavirus lineage A coronavirus, China Rattus coronavirus (ChRCoV) HKU24, from Norway rats in China. ChRCoV HKU24 occupied a deep branch at the root of members of Betacoronavirus 1, being distinct from murine coronavirus and human coronavirus HKU1. Its unique putative cleavage sites between nonstructural proteins 1 and 2 and in the spike (S) protein and low sequence identities to other lineage A betacoronaviruses (βCoVs) in conserved replicase domains support ChRCoV HKU24 as a separate species. ChRCoV HKU24 possessed genome features that resemble those of both Betacoronavirus 1 and murine coronavirus, being closer to Betacoronavirus 1 in most predicted proteins but closer to murine coronavirus by G+C content, the presence of a single nonstructural protein (NS4), and an absent transcription regulatory sequence for the envelope (E) protein. Its N-terminal domain (NTD) demonstrated higher sequence identity to the bovine coronavirus (BCoV) NTD than to the mouse hepatitis virus (MHV) NTD, with 3 of 4 critical sugar-binding residues in BCoV and 2 of 14 contact residues at the MHV NTD/murine CEACAM1a interface being conserved. Molecular clock analysis dated the time of the most recent common ancestor of ChRCoV HKU24, Betacoronavirus 1, and rabbit coronavirus HKU14 to about the year 1400. Cross-reactivities between other lineage A and B βCoVs and ChRCoV HKU24 nucleocapsid but not spike polypeptide were demonstrated. Using the spike polypeptide-based Western blot assay, we showed that only Norway rats and two oriental house rats from Guangzhou, China, were infected by ChRCoV HKU24. Other rats, including Norway rats from Hong Kong, possessed antibodies only against N protein and not against the spike polypeptide, suggesting infection by βCoVs different from ChRCoV HKU24. ChRCoV HKU24 may represent the murine origin of Betacoronavirus 1, and rodents are likely an important reservoir for ancestors of lineage A βCoVs. IMPORTANCE While bats and birds are hosts for ancestors of most coronaviruses (CoVs), lineage A βCoVs have never been found in these animals and the origin of Betacoronavirus lineage A remains obscure. We discovered a novel lineage A βCoV, China Rattus coronavirus HKU24 (ChRCoV HKU24), from Norway rats in China with a high seroprevalence. The unique genome features and phylogenetic analysis supported the suggestion that ChRCoV HKU24 represents a novel CoV species, occupying a deep branch at the root of members of Betacoronavirus 1 and being distinct from murine coronavirus. Nevertheless, ChRCoV HKU24 possessed genome characteristics that resemble those of both Betacoronavirus 1 and murine coronavirus. Our data suggest that ChRCoV HKU24 represents the murine origin of Betacoronavirus 1, with interspecies transmission from rodents to other mammals having occurred centuries ago, before the emergence of human coronavirus (HCoV) OC43 in the late 1800s. Rodents are likely an important reservoir for ancestors of lineage A βCoVs.",,"['Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Li, Kenneth S. M.', 'Tsang, Alan K. L.', 'Fan, Rachel Y. Y.', 'Luk, Hayes K. H.', 'Cai, Jian-Piao', 'Chan, Kwok-Hung', 'Zheng, Bo-Jian', 'Wang, Ming', 'Yuen, Kwok-Yung']",,,,
,PMC,Ebola Virus and Severe Acute Respiratory Syndrome Coronavirus Display Late Cell Entry Kinetics: Evidence that Transport to NPC1(+) Endolysosomes Is a Rate-Defining Step,http://dx.doi.org/10.1128/JVI.03398-14,PMC4325712,,,"Ebola virus (EBOV) causes hemorrhagic fevers with high mortality rates. During cellular entry, the virus is internalized by macropinocytosis and trafficked through endosomes until fusion between the viral and an endosomal membrane is triggered, releasing the RNA genome into the cytoplasm. We found that while macropinocytotic uptake of filamentous EBOV viruslike particles (VLPs) expressing the EBOV glycoprotein (GP) occurs relatively quickly, VLPs only begin to enter the cytoplasm after a 30-min lag, considerably later than particles bearing the influenza hemagglutinin or GP from lymphocytic choriomeningitis virus, which enter through late endosomes (LE). For EBOV, the long lag is not due to the large size or unusual shape of EBOV filaments, the need to prime EBOV GP to the 19-kDa receptor-binding species, or a need for unusually low endosomal pH. In contrast, since we observed that EBOV entry occurs upon arrival in Niemann-Pick C1 (NPC1)-positive endolysosomes (LE/Lys), we propose that trafficking to LE/Lys is a key rate-defining step. Additional experiments revealed, unexpectedly, that severe acute respiratory syndrome (SARS) S-mediated entry also begins only after a 30-min lag. Furthermore, although SARS does not require NPC1 for entry, SARS entry also begins after colocalization with NPC1. Since the only endosomal requirement for SARS entry is cathepsin L activity, we tested and provide evidence that NPC1(+) LE/Lys have higher cathepsin L activity than LE, with no detectable activity in earlier endosomes. Our findings suggest that both EBOV and SARS traffic deep into the endocytic pathway for entry and that they do so to access higher cathepsin activity. IMPORTANCE Ebola virus is a hemorrhagic fever virus that causes high fatality rates when it spreads from zoonotic vectors into the human population. Infection by severe acute respiratory syndrome coronavirus (SARS-CoV) causes severe respiratory distress in infected patients. A devastating outbreak of EBOV occurred in West Africa in 2014, and there was a significant outbreak of SARS in 2003. No effective vaccine or treatment has yet been approved for either virus. We present evidence that both viruses traffic late into the endocytic pathway, to NPC1(+) LE/Lys, in order to enter host cells, and that they do so to access high levels of cathepsin activity, which both viruses use in their fusion-triggering mechanisms. This unexpected similarity suggests an unexplored vulnerability, trafficking to NPC1(+) LE/Lys, as a therapeutic target for SARS and EBOV.",,"['Mingo, Rebecca M.', 'Simmons, James A.', 'Shoemaker, Charles J.', 'Nelson, Elizabeth A.', 'Schornberg, Kathryn L.', ""D'Souza, Ryan S."", 'Casanova, James E.', 'White, Judith M.']",,,,
,PMC,Induction and Activation of Latent Transforming Growth Factor-β(1) Are Carried out by Two Distinct Domains of Pregnancy-specific Glycoprotein 1 (PSG1),http://dx.doi.org/10.1074/jbc.M114.597518,PMC4326847,,,"Pregnancy-specific glycoproteins (PSGs) are a family of Ig-like proteins secreted by specialized placental cells. The PSG1 structure is composed of a single Ig variable region-like N-terminal domain and three Ig constant region-like domains termed A1, A2, and B2. Members of the human and murine PSG family have been shown to induce anti-inflammatory cytokines from monocytes and macrophages and to stimulate angiogenesis. We recently showed that recombinant forms of PSG1 (PSG1-Fc and PSG1-His) and PSG1 purified from the serum of pregnant women are associated with the immunoregulatory cytokine TGF-β(1) and activated latent TGF-β(1). Here, we sought to examine the requirement of specific PSG1 domains in the activation of latent TGF-β(1). Plasmon surface resonance studies showed that PSG1 directly bound to the small latent complex and to the latency-associated peptide of TGF-β(1) and that this binding was mediated through the B2 domain. Furthermore, the B2 domain alone was sufficient for activating the small latent complex. In separate experiments, we found that the PSG1-mediated induction of TGF-β(1) secretion in macrophages was dependent on the N-terminal domain. Mutagenesis analysis revealed that four amino acids (LYHY) of the CC′ loop of the N-terminal domain were required for induction of latent TGF-β(1) secretion. Together, our results show that two distinct domains of PSG1 are involved in the regulation of TGF-β(1) and provide a mechanistic framework for how PSGs modulate the immunoregulatory environment at the maternal-fetal interface for successful pregnancy outcome.",,"['Ballesteros, Angela', 'Mentink-Kane, Margaret M.', 'Warren, James', 'Kaplan, Gerardo G.', 'Dveksler, Gabriela S.']",,,,
,PMC,"The SARS-Coronavirus papain-like protease: Structure, function and inhibition by designed antiviral compounds",http://dx.doi.org/10.1016/j.antiviral.2014.12.015,PMC5896749,,,"Over ten years have passed since the deadly human coronavirus that causes severe acute respiratory syndrome (SARS-CoV) emerged from the Guangdong Province of China. Despite the fact that the SARS-CoV pandemic infected over 8,500 individuals, claimed over 800 lives and cost billions of dollars in economic loss worldwide, there still are no clinically approved antiviral drugs, vaccines or monoclonal antibody therapies to treat SARS-CoV infections. The recent emergence of the deadly human coronavirus that causes Middle East respiratory syndrome (MERS-CoV) is a sobering reminder that new and deadly coronaviruses can emerge at any time with the potential to become pandemics. Therefore, the continued development of therapeutic and prophylactic countermeasures to potentially deadly coronaviruses is warranted. The coronaviral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro), are attractive antiviral drug targets because they are essential for coronaviral replication. Although the primary function of PLpro and 3CLpro are to process the viral polyprotein in a coordinated manner, PLpro has the additional function of stripping ubiquitin and ISG15 from host-cell proteins to aid coronaviruses in their evasion of the host innate immune responses. Therefore, targeting PLpro with antiviral drugs may have an advantage in not only inhibiting viral replication but also inhibiting the dysregulation of signaling cascades in infected cells that may lead to cell death in surrounding, uninfected cells. This review provides an up-to-date discussion on the SARS-CoV papain-like protease including a brief overview of the SARS-CoV genome and replication followed by a more in-depth discussion on the structure and catalytic mechanism of SARS-CoV PLpro, the multiple cellular functions of SARS-CoV PLpro, the inhibition of SARS-CoV PLpro by small molecule inhibitors, and the prospect of inhibiting papain-like protease from other coronaviruses. This paper forms part of a series of invited articles in Antiviral Research on “ From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.”",,"['Baez-Santos, Yahira M.', 'St. John, Sarah E.', 'Mesecar, Andrew D.']",,,,
,PMC,Recombinase polymerase amplification as a promising tool in hepatitis C virus diagnosis,http://dx.doi.org/10.4254/wjh.v6.i12.916,PMC4269910,,,"Hepatitis C virus (HCV) infection represents a significant health problem and represents a heavy load on some countries like Egypt in which about 20% of the total population are infected. Initial infection is usually asymptomatic and result in chronic hepatitis that give rise to complications including cirrhosis and hepatocellular carcinoma. The management of HCV infection should not only be focus on therapy, but also to screen carrier individuals in order to prevent transmission. In the present, molecular detection and quantification of HCV genome by real time polymerase chain reaction (PCR) represent the gold standard in HCV diagnosis and plays a crucial role in the management of therapeutic regimens. However, real time PCR is a complicated approach and of limited distribution. On the other hand, isothermal DNA amplification techniques have been developed and offer molecular diagnosis of infectious dieses at point-of-care. In this review we discuss recombinase polymerase amplification technique and illustrate its diagnostic value over both PCR and other isothermal amplification techniques.",,"['Zaghloul, Hosam', 'El-shahat, Mahmoud']",,,,
,PMC,"Correlation Between Abnormal Platelet Count and Respiratory Viral Infection in Patients From Cheonan, Korea",http://dx.doi.org/10.1002/jcla.21822,PMC6806719,,,"BACKGROUND: In this study, the effects of viral infections on platelet (PLT) count have been reported. This study examined the correlation between PLT count and respiratory virus (RV) infections. METHODS: Patients who visited Dankook University Hospital between December 2006 and February 2014 with symptoms of suspected RV infection were recruited. Multiplex reverse transcriptase polymerase chain reactions identified the causative virus(es). PLT counts were analyzed with respect to virus, age and sex of the patient, and length of hospital stay. RESULTS: Of the 8,147 patients, 62.8% were RV‐positive, and 18.6% of RV‐positive patients had abnormal PLT counts. There were no differences in the rates of abnormal PLT counts between single‐infection and virus co‐infection cases. In RV infection patients, the incidence of abnormal PLT count increased with age and varied depending on the RV infection type. Patients with abnormal PLT count stayed in hospital longer than those with normal PLT count. CONCLUSIONS: The incidence of thrombocytopenia was higher among the elderly; in younger patients, thrombocytosis was more prevalent than thrombocytopenia. Respiratory tract infections caused by different viruses resulted in varied PLT count changes. Further systematic research of PLT count changes related to viral infections is required.",,"['Kim, Jae Kyung', 'Jeon, Jae‐Sik', 'Kim, Jong Wan', 'Kim, Ga‐Yeon']",,,,
,PMC,RNase L Targets Distinct Sites in Influenza A Virus RNAs,http://dx.doi.org/10.1128/JVI.02953-14,PMC4325751,,,"Influenza A virus (IAV) infections are influenced by type 1 interferon-mediated antiviral defenses and by viral countermeasures to these defenses. When IAV NS1 protein is disabled, RNase L restricts virus replication; however, the RNAs targeted for cleavage by RNase L under these conditions have not been defined. In this study, we used deep-sequencing methods to identify RNase L cleavage sites within host and viral RNAs from IAV PR8ΔNS1-infected A549 cells. Short hairpin RNA knockdown of RNase L allowed us to distinguish between RNase L-dependent and RNase L-independent cleavage sites. RNase L-dependent cleavage sites were evident at discrete locations in IAV RNA segments (both positive and negative strands). Cleavage in PB2, PB1, and PA genomic RNAs suggests that viral RNPs are susceptible to cleavage by RNase L. Prominent amounts of cleavage mapped to specific regions within IAV RNAs, including some areas of increased synonymous-site conservation. Among cellular RNAs, RNase L-dependent cleavage was most frequent at precise locations in rRNAs. Our data show that RNase L targets specific sites in both host and viral RNAs to restrict influenza virus replication when NS1 protein is disabled. IMPORTANCE RNase L is a critical component of interferon-regulated and double-stranded-RNA-activated antiviral host responses. We sought to determine how RNase L exerts its antiviral activity during influenza virus infection. We enhanced the antiviral activity of RNase L by disabling a viral protein, NS1, that inhibits the activation of RNase L. Then, using deep-sequencing methods, we identified the host and viral RNAs targeted by RNase L. We found that RNase L cleaved viral RNAs and rRNAs at very precise locations. The direct cleavage of IAV RNAs by RNase L highlights an intimate battle between viral RNAs and an antiviral endonuclease.",,"['Cooper, Daphne A.', 'Banerjee, Shuvojit', 'Chakrabarti, Arindam', 'García-Sastre, Adolfo', 'Hesselberth, Jay R.', 'Silverman, Robert H.', 'Barton, David J.']",,,,
,PMC,Testing of Middle East Respiratory Syndrome Coronavirus Replication Inhibitors for the Ability To Block Viral Entry,http://dx.doi.org/10.1128/AAC.03977-14,PMC4291393,,,,,"['Liu, Qi', 'Xia, Shuai', 'Sun, Zhiwu', 'Wang, Qian', 'Du, Lanying', 'Lu, Lu', 'Jiang, Shibo']",,,,
,PMC,Inhibition of Endoplasmic Reticulum-Resident Glucosidases Impairs Severe Acute Respiratory Syndrome Coronavirus and Human Coronavirus NL63 Spike Protein-Mediated Entry by Altering the Glycan Processing of Angiotensin I-Converting Enzyme 2,http://dx.doi.org/10.1128/AAC.03999-14,PMC4291352,,,"Endoplasmic reticulum (ER)-resident glucosidases I and II sequentially trim the three terminal glucose moieties on the N-linked glycans attached to nascent glycoproteins. These reactions are the first steps of N-linked glycan processing and are essential for proper folding and function of many glycoproteins. Because most of the viral envelope glycoproteins contain N-linked glycans, inhibition of ER glucosidases with derivatives of 1-deoxynojirimycin, i.e., iminosugars, efficiently disrupts the morphogenesis of a broad spectrum of enveloped viruses. However, like viral envelope proteins, the cellular receptors of many viruses are also glycoproteins. It is therefore possible that inhibition of ER glucosidases not only compromises virion production but also disrupts expression and function of viral receptors and thus inhibits virus entry into host cells. Indeed, we demonstrate here that iminosugar treatment altered the N-linked glycan structure of angiotensin I-converting enzyme 2 (ACE2), which did not affect its expression on the cell surface or its binding of the severe acute respiratory syndrome coronavirus (SARS-CoV) spike glycoprotein. However, alteration of N-linked glycans of ACE2 impaired its ability to support the transduction of SARS-CoV and human coronavirus NL63 (HCoV-NL63) spike glycoprotein-pseudotyped lentiviral particles by disruption of the viral envelope protein-triggered membrane fusion. Hence, in addition to reducing the production of infectious virions, inhibition of ER glucosidases also impairs the entry of selected viruses via a post-receptor-binding mechanism.",,"['Zhao, Xuesen', 'Guo, Fang', 'Comunale, Mary Ann', 'Mehta, Anand', 'Sehgal, Mohit', 'Jain, Pooja', 'Cuconati, Andrea', 'Lin, Hanxin', 'Block, Timothy M.', 'Chang, Jinhong', 'Guo, Ju-Tao']",,,,
,PMC,Sequencing the functional antibody repertoire—diagnostic and therapeutic discovery,http://dx.doi.org/10.1038/nrrheum.2014.220,PMC4382308,,,"The development of high-throughput DNA sequencing technologies has enabled large-scale characterization of functional antibody repertoires, a new method of understanding protective and pathogenic immune responses. Important parameters to consider when sequencing antibody repertoires include the methodology, the B-cell population and clinical characteristics of the individuals analysed, and the bioinformatic analysis. Although focused sequencing of immunoglobulin heavy chains or complement determining regions can be utilized to monitor particular immune responses and B-cell malignancies, high-fidelity analysis of the full-length paired heavy and light chains expressed by individual B cells is critical for characterizing functional antibody repertoires. Bioinformatic identification of clonal antibody families and recombinant expression of representative members produces recombinant antibodies that can be used to identify the antigen targets of functional immune responses and to investigate the mechanisms of their protective or pathogenic functions. Integrated analysis of coexpressed functional genes provides the potential to further pinpoint the most important antibodies and clonal families generated during an immune response. Sequencing antibody repertoires is transforming our understanding of immune responses to autoimmunity, vaccination, infection and cancer. We anticipate that antibody repertoire sequencing will provide next-generation biomarkers, diagnostic tools and therapeutic antibodies for a spectrum of diseases, including rheumatic diseases.",,"Robinson, William H.",,,,
,PMC,A Sorting Signal Suppresses IFITM1 Restriction of Viral Entry,http://dx.doi.org/10.1074/jbc.M114.630780,PMC4326833,,,"The interferon-induced transmembrane proteins (IFITMs) broadly inhibit virus infections, particularly at the viral entry level. However, despite this shared ability to inhibit fusion, IFITMs differ in the potency and breadth of viruses restricted, an anomaly that is not fully understood. Here, we show that differences in the range of viruses restricted by IFITM1 are regulated by a C-terminal non-canonical dibasic sorting signal KRXX that suppresses restriction of some viruses by governing its intracellular distribution. Replacing the two basic residues with alanine (KR/AA) increased restriction of jaagsiekte sheep retrovirus and 10A1 amphotropic murine leukemia virus. Deconvolution microscopy revealed an altered subcellular distribution for KR/AA, with fewer molecules in LAMP1-positive lysosomes balanced by increased levels in CD63-positive multivesicular bodies, where jaagsiekte sheep retrovirus pseudovirions are colocalized. IFITM1 binds to cellular adaptor protein complex 3 (AP-3), an association that is lost when the dibasic motif is altered. Although knockdown of AP-3 itself decreases some virus entry, expression of parental IFITM1, but not its KR/AA mutant, potentiates inhibition of viral infections in AP-3 knockdown cells. By using the substituted cysteine accessibility method, we provide evidence that IFITM1 adopts more than one membrane topology co-existing in cellular membranes. Because the C-terminal dibasic sorting signal is unique to human IFITM1, our results provide novel insight into understanding the species- and virus-specific antiviral effect of IFITMs.",,"['Li, Kun', 'Jia, Rui', 'Li, Minghua', 'Zheng, Yi-Min', 'Miao, Chunhui', 'Yao, Yunfang', 'Ji, Hong-Long', 'Geng, Yunqi', 'Qiao, Wentao', 'Albritton, Lorraine M.', 'Liang, Chen', 'Liu, Shan-Lu']",,,,
,PMC,Reservoir Host Immune Responses to Emerging Zoonotic Viruses,http://dx.doi.org/10.1016/j.cell.2014.12.003,PMC4390999,,,"Zoonotic viruses, such as HIV, Ebola virus, coronaviruses, influenza A viruses, hantaviruses, or henipaviruses, can result in profound pathology in humans. In contrast, populations of the reservoir hosts of zoonotic pathogens often appear to tolerate these infections with little evidence of disease. Why are viruses more dangerous in one species than another? Immunological studies investigating quantitative and qualitative differences in the host-virus equilibrium in animal reservoirs will be key to answering this question, informing new approaches for treating and preventing zoonotic diseases. Integrating an understanding of host immune responses with epidemiological, ecological, and evolutionary insights into viral emergence will shed light on mechanisms that minimize fitness costs associated with viral infection, facilitate transmission to other hosts, and underlie the association of specific reservoir hosts with multiple emerging viruses. Reservoir host studies provide a rich opportunity for elucidating fundamental immunological processes and their underlying genetic basis, in the context of distinct physiological and metabolic constraints that contribute to host resistance and disease tolerance.",,"['Mandl, Judith N.', 'Ahmed, Rafi', 'Barreiro, Luis B.', 'Daszak, Peter', 'Epstein, Jonathan H.', 'Virgin, Herbert W.', 'Feinberg, Mark B.']",,,,
,PMC,"Family Clusters of Avian Influenza A H7N9 Virus Infection in Guangdong Province, China",http://dx.doi.org/10.1128/JCM.02322-14,PMC4290927,,,"Since its first identification, the epizootic avian influenza A H7N9 virus has continued to cause infections in China. Two waves were observed during this outbreak. No cases were reported from Guangdong Province during the first wave, but this province became one of the prime outbreak sites during the second wave. In order to identify the transmission potential of this continuously evolving infectious virus, our research group monitored all clusters of H7N9 infections during the second wave of the epidemic in Guangdong Province. Epidemiological, clinical, and virological data on these patients were collected and analyzed. Three family clusters including six cases of H7N9 infection were recorded. The virus caused severe disease in two adult patients but only mild symptoms for all four pediatric patients. All patients reported direct poultry or poultry market exposure history. Relevant environment samples collected according to their reported exposures tested H7N9 positive. Virus isolates from patients in the same cluster shared high sequence similarities. In conclusion, although continually evolving, the currently circulating H7N9 viruses in Guangdong Province have not yet demonstrated the capacity for efficient and sustained person-to-person transmission.",,"['Yi, Lina', 'Guan, Dawei', 'Kang, Min', 'Wu, Jie', 'Zeng, Xianqiao', 'Lu, Jing', 'Rutherford, Shannon', 'Zou, Lirong', 'Liang, Lijun', 'Ni, Hanzhong', 'Zhang, Xin', 'Zhong, Haojie', 'He, Jianfeng', 'Lin, Jinyan', 'Ke, Changwen']",,,,
,PMC,DNA Microarray for Detection of Gastrointestinal Viruses,http://dx.doi.org/10.1128/JCM.01317-14,PMC4290912,,,"Gastroenteritis is a clinical illness of humans and other animals that is characterized by vomiting and diarrhea and caused by a variety of pathogens, including viruses. An increasing number of viral species have been associated with gastroenteritis or have been found in stool samples as new molecular tools have been developed. In this work, a DNA microarray capable in theory of parallel detection of more than 100 viral species was developed and tested. Initial validation was done with 10 different virus species, and an additional 5 species were validated using clinical samples. Detection limits of 1 × 10(3) virus particles of Human adenovirus C (HAdV), Human astrovirus (HAstV), and group A Rotavirus (RV-A) were established. Furthermore, when exogenous RNA was added, the limit for RV-A detection decreased by one log. In a small group of clinical samples from children with gastroenteritis (n = 76), the microarray detected at least one viral species in 92% of the samples. Single infection was identified in 63 samples (83%), and coinfection with more than one virus was identified in 7 samples (9%). The most abundant virus species were RV-A (58%), followed by Anellovirus (15.8%), HAstV (6.6%), HAdV (5.3%), Norwalk virus (6.6%), Human enterovirus (HEV) (9.2%), Human parechovirus (1.3%), Sapporo virus (1.3%), and Human bocavirus (1.3%). To further test the specificity and sensitivity of the microarray, the results were verified by reverse transcription-PCR (RT-PCR) detection of 5 gastrointestinal viruses. The RT-PCR assay detected a virus in 59 samples (78%). The microarray showed good performance for detection of RV-A, HAstV, and calicivirus, while the sensitivity for HAdV and HEV was low. Furthermore, some discrepancies in detection of mixed infections were observed and were addressed by reverse transcription-quantitative PCR (RT-qPCR) of the viruses involved. It was observed that differences in the amount of genetic material favored the detection of the most abundant virus. The microarray described in this work should help in understanding the etiology of gastroenteritis in humans and animals.",,"['Martínez, Miguel A.', 'Soto-del Río, María de los Dolores', 'Gutiérrez, Rosa María', 'Chiu, Charles Y.', 'Greninger, Alexander L.', 'Contreras, Juan Francisco', 'López, Susana', 'Arias, Carlos F.', 'Isa, Pavel']",,,,
,PMC,Estimation of MERS-Coronavirus Reproductive Number and Case Fatality Rate for the Spring 2014 Saudi Arabia Outbreak: Insights from Publicly Available Data,http://dx.doi.org/10.1371/currents.outbreaks.98d2f8f3382d84f390736cd5f5fe133c,PMC4322060,25685622,CC BY,"Background: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was initially recognized as a source of severe respiratory illness and renal failure in 2012. Prior to 2014, MERS-CoV was mostly associated with sporadic cases of human illness, of presumed zoonotic origin, though chains of person-to-person transmission in the healthcare setting were reported. In spring 2014, large healthcare-associated outbreaks of MERS-CoV infection occurred in Jeddah and Riyadh, Kingdom of Saudi Arabia. To date the epidemiological information published by public health investigators in affected jurisdictions has been relatively limited. However, it is important that the global public health community have access to information on the basic epidemiological features of the outbreak to date, including the basic reproduction number (R0) and best estimates of case-fatality rates (CFR). We sought to address these gaps using a publicly available line listing of MERS-CoV cases. Methods: R0 was estimated using the incidence decay with exponential adjustment (“IDEA”) method, while period-specific case fatality rates that incorporated non-attributed death data were estimated using Monte Carlo simulation. Results: 707 cases were available for evaluation. 52% of cases were identified as primary, with the rest being secondary. IDEA model fits suggested a higher R0 in Jeddah (3.5-6.7) than in Riyadh (2.0-2.8); control parameters suggested more rapid reduction in transmission in the former city than the latter. The model accurately projected final size and end date of the Riyadh outbreak based on information available prior to the outbreak peak; for Jeddah, these projections were possible once the outbreak peaked. Overall case-fatality was 40%; depending on the timing of 171 deaths unlinked to case data, outbreak CFR could be higher, lower, or equivalent to pre-outbreak CFR. Conclusions: Notwithstanding imperfect data, inferences about MERS-CoV epidemiology important for public health preparedness are possible using publicly available data sources. The R0 estimated in Riyadh appears similar to that seen for SARS-CoV, but CFR appears higher, and indirect evidence suggests control activities ended these outbreaks. These data suggest this disease should be regarded with equal or greater concern than the related SARS-CoV.",2014 Dec 18,"['Majumder, Maimuna S.', 'Rivers, Caitlin', 'Lofgren, Eric', 'Fisman, David']",PLoS Curr,,,
,PMC,Severe Acute Respiratory Syndrome-Associated Coronavirus Vaccines Formulated with Delta Inulin Adjuvants Provide Enhanced Protection while Ameliorating Lung Eosinophilic Immunopathology,http://dx.doi.org/10.1128/JVI.02980-14,PMC4337527,,,"Although the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) epidemic was controlled by nonvaccine measures, coronaviruses remain a major threat to human health. The design of optimal coronavirus vaccines therefore remains a priority. Such vaccines present major challenges: coronavirus immunity often wanes rapidly, individuals needing to be protected include the elderly, and vaccines may exacerbate rather than prevent coronavirus lung immunopathology. To address these issues, we compared in a murine model a range of recombinant spike protein or inactivated whole-virus vaccine candidates alone or adjuvanted with either alum, CpG, or Advax, a new delta inulin-based polysaccharide adjuvant. While all vaccines protected against lethal infection, addition of adjuvant significantly increased serum neutralizing-antibody titers and reduced lung virus titers on day 3 postchallenge. Whereas unadjuvanted or alum-formulated vaccines were associated with significantly increased lung eosinophilic immunopathology on day 6 postchallenge, this was not seen in mice immunized with vaccines formulated with delta inulin adjuvant. Protection against eosinophilic immunopathology by vaccines containing delta inulin adjuvants correlated better with enhanced T-cell gamma interferon (IFN-γ) recall responses rather than reduced interleukin-4 (IL-4) responses, suggesting that immunopathology predominantly reflects an inadequate vaccine-induced Th1 response. This study highlights the critical importance for development of effective and safe coronavirus vaccines of selection of adjuvants based on the ability to induce durable IFN-γ responses. IMPORTANCE Coronaviruses such as SARS-CoV and Middle East respiratory syndrome-associated coronavirus (MERS-CoV) cause high case fatality rates and remain major human public health threats, creating a need for effective vaccines. While coronavirus antigens that induce protective neutralizing antibodies have been identified, coronavirus vaccines present a unique problem in that immunized individuals when infected by virus can develop lung eosinophilic pathology, a problem that is further exacerbated by the formulation of SARS-CoV vaccines with alum adjuvants. This study shows that formulation of SARS-CoV spike protein or inactivated whole-virus vaccines with novel delta inulin-based polysaccharide adjuvants enhances neutralizing-antibody titers and protection against clinical disease but at the same time also protects against development of lung eosinophilic immunopathology. It also shows that immunity achieved with delta inulin adjuvants is long-lived, thereby overcoming the natural tendency for rapidly waning coronavirus immunity. Thus, delta inulin adjuvants may offer a unique ability to develop safer and more effective coronavirus vaccines.",,"['Honda-Okubo, Yoshikazu', 'Barnard, Dale', 'Ong, Chun Hao', 'Peng, Bi-Hung', 'Tseng, Chien-Te Kent', 'Petrovsky, Nikolai']",,,,
,PMC,Correlates of virulence in a frog-killing fungal pathogen: evidence from a California amphibian decline,http://dx.doi.org/10.1038/ismej.2014.241,PMC4478697,,,"The fungal pathogen Batrachochytrium dendrobatidis (Bd) has caused declines and extinctions in amphibians worldwide, and there is increasing evidence that some strains of this pathogen are more virulent than others. While a number of putative virulence factors have been identified, few studies link these factors to specific epizootic events. We documented a dramatic decline in juvenile frogs in a Bd-infected population of Cascades frogs (Rana cascadae) in the mountains of northern California and used a laboratory experiment to show that Bd isolated in the midst of this decline induced higher mortality than Bd isolated from a more stable population of the same species of frog. This highly virulent Bd isolate was more toxic to immune cells and attained higher density in liquid culture than comparable isolates. Genomic analyses revealed that this isolate is nested within the global panzootic lineage and exhibited unusual genomic patterns, including increased copy numbers of many chromosomal segments. This study integrates data from multiple sources to suggest specific phenotypic and genomic characteristics of the pathogen that may be linked to disease-related declines.",,"['Piovia-Scott, Jonah', 'Pope, Karen', 'Joy Worth, S', 'Rosenblum, Erica Bree', 'Poorten, Thomas', 'Refsnider, Jeanine', 'Rollins-Smith, Louise A', 'Reinert, Laura K', 'Wells, Heather L', 'Rejmanek, Dan', 'Lawler, Sharon', 'Foley, Janet']",,,,
,PMC,Homeostatic interferon expression in neurons is sufficient for early control of viral infection,http://dx.doi.org/10.1016/j.jneuroim.2014.12.012,PMC4325274,,,"The mechanisms by which neurons respond to inflammatory mediators such as interferons (IFNs) remain largely undefined. We previously showed that the activation and nuclear localization of the core IFN signaling molecule, Stat1, are muted and delayed in primary mouse hippocampal neurons treated with IFN gamma as compared to control mouse embryonic fibroblasts (MEF). Here, we show that the kinetics of Stat1 and Stat2 activation following type I IFN exposure are also unique in neurons, affecting gene expression and neuronal response. Specifically, despite lower basal expression of many IFN stimulated genes in neurons, basal expression of the type I IFN themselves is significantly higher in primary hippocampal neurons compared to MEF. Elevated homeostatic IFN in neurons is critical and sufficient for early control of viral infection. These data provide further evidence that neurons exploit unique signaling responses to IFNs, and define an important contribution of homeostatic IFN within the CNS. Such differences are likely critical for the ability of neurons to survive a viral challenge.",,"['Cavanaugh, Sarah E.', 'Holmgren, Alicia M.', 'Rall, Glenn F.']",,,,
,PMC,Simian Hemorrhagic Fever Virus Cell Entry Is Dependent on CD163 and Uses a Clathrin-Mediated Endocytosis-Like Pathway,http://dx.doi.org/10.1128/JVI.02697-14,PMC4301170,,,"Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral hemorrhagic fever in Asian macaques but is thought to be nonpathogenic for humans. To date, the SHFV life cycle is almost completely uncharacterized on the molecular level. Here, we describe the first steps of the SHFV life cycle. Our experiments indicate that SHFV enters target cells by low-pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-β-cyclodextrin, chloroquine, and concanamycin A dramatically reduced SHFV entry efficiency, whereas the macropinocytosis inhibitors EIPA, blebbistatin, and wortmannin and the caveolin-mediated endocytosis inhibitors nystatin and filipin III had no effect. Furthermore, overexpression and knockout study and electron microscopy results indicate that SHFV entry occurs by a dynamin-dependent clathrin-mediated endocytosis-like pathway. Experiments utilizing latrunculin B, cytochalasin B, and cytochalasin D indicate that SHFV does not hijack the actin polymerization pathway. Treatment of target cells with proteases (proteinase K, papain, α-chymotrypsin, and trypsin) abrogated entry, indicating that the SHFV cell surface receptor is a protein. Phospholipases A2 and D had no effect on SHFV entry. Finally, treatment of cells with antibodies targeting CD163, a cell surface molecule identified as an entry factor for the SHFV-related porcine reproductive and respiratory syndrome virus, diminished SHFV replication, identifying CD163 as an important SHFV entry component. IMPORTANCE Simian hemorrhagic fever virus (SHFV) causes highly lethal disease in Asian macaques resembling human illness caused by Ebola or Lassa virus. However, little is known about SHFV's ecology and molecular biology and the mechanism by which it causes disease. The results of this study shed light on how SHFV enters its target cells. Using electron microscopy and inhibitors for various cellular pathways, we demonstrate that SHFV invades cells by low-pH-dependent, actin-independent endocytosis, likely with the help of a cellular surface protein.",,"['Caì, Yíngyún', 'Postnikova, Elena N.', 'Bernbaum, John G.', 'Yú, Shuǐqìng', 'Mazur, Steven', 'Deiuliis, Nicole M.', 'Radoshitzky, Sheli R.', 'Lackemeyer, Matthew G.', 'McCluskey, Adam', 'Robinson, Phillip J.', 'Haucke, Volker', 'Wahl-Jensen, Victoria', 'Bailey, Adam L.', 'Lauck, Michael', 'Friedrich, Thomas C.', ""O'Connor, David H."", 'Goldberg, Tony L.', 'Jahrling, Peter B.', 'Kuhn, Jens H.']",,,,
,PMC,Perturbation in the Conserved Methyltransferase-Polymerase Interface of Flavivirus NS5 Differentially Affects Polymerase Initiation and Elongation,http://dx.doi.org/10.1128/JVI.02085-14,PMC4301151,,,"The flavivirus NS5 is a natural fusion of a methyltransferase (MTase) and an RNA-dependent RNA polymerase (RdRP). Analogous to DNA-dependent RNA polymerases, the NS5 polymerase initiates RNA synthesis through a de novo mechanism and then makes a transition to a processive elongation phase. However, whether and how the MTase affects polymerase activities through intramolecular interactions remain elusive. By solving the crystal structure of the Japanese encephalitis virus (JEV) NS5, we recently identified an MTase-RdRP interface containing a set of six hydrophobic residues highly conserved among flaviviruses. To dissect the functional relevance of this interface, we made a series of JEV NS5 constructs with mutations of these hydrophobic residues and/or with the N-terminal first 261 residues and other residues up to the first 303 residues deleted. Compared to the wild-type (WT) NS5, full-length NS5 variants exhibited consistent up- or downregulation of the initiation activities in two types of polymerase assays. Five representative full-length NS5 constructs were then tested in an elongation assay, from which the apparent single-nucleotide incorporation rate constant was estimated. Interestingly, two constructs exhibited different elongation kinetics from the WT NS5, with an effect rather opposite to what was observed at initiation. Moreover, constructs with MTase and/or the linker region (residues 266 to 275) removed still retained polymerase activities, albeit at overall lower levels. However, further removal of the N-terminal extension (residues 276 to 303) abolished regular template-directed synthesis. Together, our data showed that the MTase-RdRP interface is relevant in both polymerase initiation and elongation, likely with different regulation mechanisms in these two major phases of RNA synthesis. IMPORTANCE The flavivirus NS5 is very unique in having a methyltransferase (MTase) placed on the immediate N terminus of its RNA-dependent RNA polymerase (RdRP). We recently solved the crystal structure of the full-length NS5, which revealed a conserved interface between MTase and RdRP. Building on this discovery, here we carried out in vitro polymerase assays to address the functional relevance of the interface interactions. By explicitly probing polymerase initiation and elongation activities, we found that perturbation in the MTase-RdRP interface had different impacts on different phases of synthesis, suggesting that the roles and contribution of the interface interactions may change upon phase transitions. By comparing the N-terminal-truncated enzymes with the full-length NS5, we collected data to indicate the indispensability to regular polymerase activities of a region that was functionally unclarified previously. Taken together, we provide biochemical evidence and mechanistic insights for the cross talk between the two enzyme modules of flavivirus NS5.",,"['Wu, Jiqin', 'Lu, Guoliang', 'Zhang, Bo', 'Gong, Peng']",,,,
,PMC,Impact and Regulation of Lambda Interferon Response in Human Metapneumovirus Infection,http://dx.doi.org/10.1128/JVI.02897-14,PMC4301146,,,"Human metapneumovirus (hMPV) is a respiratory paramyxovirus that is distributed worldwide and induces significant airway morbidity. Despite the relevance of hMPV as a pathogen, many aspects of the immune response to this virus are still largely unknown. In this report, we focus on the antiviral immune response, which is critical for viral clearance and disease resolution. Using in vitro and in vivo systems, we show that hMPV is able to induce expression of lambda interferon 1 (IFN-λ1), IFN-λ2, IFN-λ3, and IFN-λ4. The induction of IFN-λ expression by hMPV was dependent on interferon regulatory factor 7 (IRF-7) expression but not on IRF-3 expression. Treatment of hMPV-infected mice with IFN-λ reduced the disease severity, lung viral titer, and inflammatory response in the lung. Moreover, the IFN-λ response induced by the virus was regulated by the expression of the hMPV G protein. These results show that type III interferons (IFN-λs) play a critical protective role in hMPV infection. IMPORTANCE Human metapneumovirus (hMPV) is a pathogen of worldwide importance. Despite the relevance of hMPV as a pathogen, critical aspects of the immune response induced by this virus remain unidentified. Interferons (IFNs), including IFN-λ, the newest addition to the interferon family, constitute an indispensable part of the innate immune response. Here, we demonstrated that IFN-λ exhibited a protective role in hMPV infection in vitro and in an experimental mouse model of infection.",,"['Baños-Lara, Ma. Del Rocío', 'Harvey, Lindsey', 'Mendoza, Alexander', 'Simms, Dawn', 'Chouljenko, Vladimir N.', 'Wakamatsu, Nobuko', 'Kousoulas, K. Gus', 'Guerrero-Plata, Antonieta']",,,,
,PMC,Swine Interferon-Inducible Transmembrane Proteins Potently Inhibit Influenza A Virus Replication,http://dx.doi.org/10.1128/JVI.02516-14,PMC4301123,,,"Human interferon-inducible transmembrane proteins (IFITMs) were identified as restriction factors of influenza A virus (IAV). Given the important role of pigs in the zoonotic cycle of IAV, we cloned swine IFITMs (swIFITMs) and found two IFITM1-like proteins, one homologue of IFITM2, and a homologue of IFITM3. We show that swIFITM2 and swIFITM3 localize to endosomes and display potent antiviral activities. Knockdown of swIFITMs strongly reduced virus inhibition by interferon, establishing the swIFITMs as potent restriction factors in porcine cells.",,"['Lanz, Caroline', 'Yángüez, Emilio', 'Andenmatten, Dario', 'Stertz, Silke']",,,,
,PMC,Kaposi's Sarcoma-Associated Herpesvirus-Encoded Replication and Transcription Activator Impairs Innate Immunity via Ubiquitin-Mediated Degradation of Myeloid Differentiation Factor 88,http://dx.doi.org/10.1128/JVI.02591-14,PMC4301122,,,"Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus with latent and lytic reactivation cycles. The mechanism by which KSHV evades the innate immune system to establish latency has not yet been precisely elucidated. Toll-like receptors (TLRs) are the first line of defense against viral infections. Myeloid differentiation factor 88 (MyD88) is a key adaptor that interacts with all TLRs except TLR3 to produce inflammatory factors and type I interferons (IFNs), which are central components of innate immunity against microbial infection. Here, we found that KSHV replication and transcription activator (RTA), which is an immediate-early master switch protein of viral cycles, downregulates MyD88 expression at the protein level by degrading MyD88 through the ubiquitin (Ub)-proteasome pathway. We identified the interaction between RTA and MyD88 in vitro and in vivo and demonstrated that RTA functions as an E3 ligase to ubiquitinate MyD88. MyD88 also was repressed at the early stage of de novo infection as well as in lytic reactivation. We also found that RTA inhibited lipopolysaccharide (LPS)-triggered activation of the TLR4 pathway by reducing IFN production and NF-κB activity. Finally, we showed that MyD88 promoted the production of IFNs and inhibited KSHV LANA-1 gene transcription. Taken together, our results suggest that KSHV RTA facilitates the virus to evade innate immunity through the degradation of MyD88, which might be critical for viral latency control. IMPORTANCE MyD88 is an adaptor for all TLRs other than TLR3, and it mediates inflammatory factors and IFN production. Our study demonstrated that the KSHV RTA protein functions as an E3 ligase to degrade MyD88 through the ubiquitin-proteasome pathway and block the transmission of TLRs signals. Moreover, we found that KSHV inhibited MyD88 expression during the early stage of de novo infection as well as in lytic reactivation. These results provide a potential mechanism for the virus to evade innate immunity.",,"['Zhao, Qinglan', 'Liang, Deguang', 'Sun, Rui', 'Jia, Baosen', 'Xia, Tian', 'Xiao, Hui', 'Lan, Ke']",,,,
,PMC,"Variations in pH Sensitivity, Acid Stability, and Fusogenicity of Three Influenza Virus H3 Subtypes",http://dx.doi.org/10.1128/JVI.01927-14,PMC4301117,,,"Influenza A virus strains adapt to achieve successful entry into host species. Entry is mediated by the viral membrane protein hemagglutinin (HA), which triggers membrane fusion and genome release under acidic conditions in the endosome. In addition to changes in the receptor binding domain, the acid stability of HA has been linked to the successful transmission of virus between avian and human hosts. However, to fully understand the connection between changes in HA and host tropism, additional factors relevant to HA structure-function and membrane fusion are also likely to be important. Using single-particle-tracking (SPT) techniques, individual membrane fusion events can be observed under specific conditions, which provide detailed information regarding HA pH sensitivity and acid stability and the rate and extent of membrane fusion. This provides a comparative way to characterize and distinguish influenza virus fusion properties among virus strains. We used SPT to quantify the fusion properties of three H3 influenza strains: A/Aichi/68/H3N2 (X:31), A/Udorn/72/H3N2 (Udorn), and A/Brisbane/07/H3N2 (Brisbane). The rate of fusion for the most clinically relevant strain, Brisbane, is generally insensitive to decreasing pH, while the fusion of the egg-adapted strains Udorn and X:31 is strongly dependent on pH (and is faster) as the pH decreases. All strains exhibit similar acid stability (the length of time that they remain fusogenic in an acidic environment) at higher pHs, but the egg-adapted strains become less acid stable at lower pHs. Thus, it appears that the laboratory-adapted H3 strains tested may have evolved to compensate for the faster HA deactivation at low pH, with a commensurate increase in the rate of fusion and number of proteins facilitating fusion, relative to the Brisbane strain. IMPORTANCE The ability of influenza virus to release its genome under different acidic conditions has recently been linked to the transmission of influenza virus between different species. However, it is yet to be determined how acid-induced membrane fusion varies with virus strain and influences tropism. The results presented here are the results of an intra-H3-subtype study of acid stability and fusion kinetics. Using a single-particle-tracking (SPT) technique, we show here that the highest pH that initiates fusion is not necessarily the pH at which the kinetics of fusion is fastest and most abundant for a given strain. Strains exhibit different fusion behaviors, as evidenced by their unique kinetic trends; pH sensitivities, as evidenced by the differences when the first fusion events commence; and HA stabilities, as evidenced by the length of time that virions can persist in an acidic environment and still be fusion competent.",,"['Costello, Deirdre A.', 'Whittaker, Gary R.', 'Daniel, Susan']",,,,
,PMC,Rhabdovirus-Based Vaccine Platforms against Henipaviruses,http://dx.doi.org/10.1128/JVI.02308-14,PMC4301098,,,"The emerging zoonotic pathogens Hendra virus (HeV) and Nipah virus (NiV) are in the genus Henipavirus in the family Paramyxoviridae. HeV and NiV infections can be highly fatal to humans and livestock. The goal of this study was to develop candidate vaccines against henipaviruses utilizing two well-established rhabdoviral vaccine vector platforms, recombinant rabies virus (RABV) and recombinant vesicular stomatitis virus (VSV), expressing either the codon-optimized or the wild-type (wt) HeV glycoprotein (G) gene. The RABV vector expressing the codon-optimized HeV G showed a 2- to 3-fold increase in incorporation compared to the RABV vector expressing wt HeV G. There was no significant difference in HeV G incorporation in the VSV vectors expressing either wt or codon-optimized HeV G. Mice inoculated intranasally with any of these live recombinant viruses showed no signs of disease, including weight loss, indicating that HeV G expression and incorporation did not increase the neurotropism of the vaccine vectors. To test the immunogenicity of the vaccine candidates, we immunized mice intramuscularly with either one dose of the live vaccines or 3 doses of 10 μg chemically inactivated viral particles. Increased codon-optimized HeV G incorporation into RABV virions resulted in higher antibody titers against HeV G compared to inactivated RABV virions expressing wt HeV G. The live VSV vectors induced more HeV G-specific antibodies as well as higher levels of HeV neutralizing antibodies than the RABV vectors. In the case of killed particles, HeV neutralizing serum titers were very similar between the two platforms. These results indicated that killed RABV with codon-optimized HeV G should be the vector of choice as a dual vaccine in areas where rabies is endemic. IMPORTANCE Scientists have been tracking two new viruses carried by the Pteropid fruit bats: Hendra virus (HeV) and Nipah virus (NiV). Both viruses can be fatal to humans and also pose a serious risk to domestic animals. A recent escalation in the frequency of outbreaks has increased the need for a vaccine that prevents HeV and NiV infections. In this study, we performed an extensive comparison of live and killed particles of two recombinant rhabdoviral vectors, rabies virus and vesicular stomatitis virus (VSV), expressing wild-type or codon-optimized HeV glycoprotein, with the goal of developing a candidate vaccine against HeV. Based on our data from the presented mouse immunogenicity studies, we conclude that a killed RABV vaccine would be highly effective against HeV infections and would make an excellent vaccine candidate in areas where both RABV and henipaviruses pose a threat to human health.",,"['Kurup, Drishya', 'Wirblich, Christoph', 'Feldmann, Heinz', 'Marzi, Andrea', 'Schnell, Matthias J.']",,,,
,PMC,Quantitative Proteomics Identifies Host Factors Modulated during Acute Hepatitis E Virus Infection in the Swine Model,http://dx.doi.org/10.1128/JVI.02208-14,PMC4301096,,,"Hepatitis E virus (HEV) causes acute enterically transmitted hepatitis. In industrialized countries, it is a zoonotic disease, with swine being the major reservoir of human HEV contamination. The occurrence and severity of the disease are variable, with clinical symptoms ranging from asymptomatic to self-limiting acute hepatitis, chronic infection, or fulminant hepatitis. In the absence of a robust cell culture system or small-animal models, the HEV life cycle and pathological process remain unclear. To characterize HEV pathogenesis and virulence mechanisms, a quantitative proteomic analysis was carried out to identify cellular factors and pathways modulated during acute infection of swine. Three groups of pigs were inoculated with three different strains of swine HEV to evaluate the possible role of viral determinants in pathogenesis. Liver samples were analyzed by a differential proteomic approach, two-dimensional difference in gel electrophoresis, and 61 modulated proteins were identified by mass spectroscopy. The results obtained show that the three HEV strains replicate similarly in swine and that they modulate several cellular pathways, suggesting that HEV impairs several cellular processes, which can account for the various types of disease expression. Several proteins, such as heterogeneous nuclear ribonucleoprotein K, apolipoprotein E, and prohibitin, known to be involved in other viral life cycles, were upregulated in HEV-infected livers. Some differences were observed between the three strains, suggesting that HEV's genetic variability may induce variations in pathogenesis. This comparative analysis of the liver proteome modulated during infection with three different strains of HEV genotype 3 provides an important basis for further investigations on the factors involved in HEV replication and the mechanism of HEV pathogenesis. IMPORTANCE Hepatitis E virus (HEV) is responsible for acute hepatitis, with clinical symptoms ranging from asymptomatic to self-limiting acute hepatitis, chronic infection, or fulminant hepatitis. In industrialized countries, HEV is considered an emerging zoonotic disease, with swine being the principal reservoir for human contamination. The viral and cellular factors involved in the replication and/or pathogenesis of HEV are still not fully known. Here we report that several cellular pathways involved in cholesterol and lipid metabolism or cell survival were modulated during HEV infection in the swine model. Moreover, we observed a difference between the different swine strains, suggesting that HEV's genetic variability could play a role in pathogenesis. We also identified some proteins known to be involved in other viral cycles. Our study provides insight into the mechanisms modulated during HEV infection and constitutes a useful reference for future work on HEV pathogenesis and virulence.",,"['Rogée, Sophie', 'Le Gall, Morgane', 'Chafey, Philippe', 'Bouquet, Jérôme', 'Cordonnier, Nathalie', 'Frederici, Christian', 'Pavio, Nicole']",,,,
,PMC,The Medical Biochemistry of Poverty and Neglect,http://dx.doi.org/10.2119/molmed.2014.00169,PMC4374519,,,,,"Hotez, Peter J",,,,
,PMC,ER Morphology: Sculpting with XendoU,http://dx.doi.org/10.1016/j.cub.2014.11.005,PMC5585780,,,"Endoplasmic reticulum (ER) sheet membranes are covered with ribosomes and RNAs that are involved in protein synthesis. A new study reveals that a calcium-activated endoribonuclease of the EndoU protein family promotes the formation of tubular ER networks, contributing to dynamic shaping of the ER in cells.",,"['Zhao, Guohua', 'Blackstone, Craig']",,,,
,PMC,Economic optimization of a global strategy to address the pandemic threat,http://dx.doi.org/10.1073/pnas.1412661112,PMC4284561,,,"Emerging pandemics threaten global health and economies and are increasing in frequency. Globally coordinated strategies to combat pandemics, similar to current strategies that address climate change, are largely adaptive, in that they attempt to reduce the impact of a pathogen after it has emerged. However, like climate change, mitigation strategies have been developed that include programs to reduce the underlying drivers of pandemics, particularly animal-to-human disease transmission. Here, we use real options economic modeling of current globally coordinated adaptation strategies for pandemic prevention. We show that they would be optimally implemented within 27 y to reduce the annual rise of emerging infectious disease events by 50% at an estimated one-time cost of approximately $343.7 billion. We then analyze World Bank data on multilateral “One Health” pandemic mitigation programs. We find that, because most pandemics have animal origins, mitigation is a more cost-effective policy than business-as-usual adaptation programs, saving between $344.0.7 billion and $360.3 billion over the next 100 y if implemented today. We conclude that globally coordinated pandemic prevention policies need to be enacted urgently to be optimally effective and that strategies to mitigate pandemics by reducing the impact of their underlying drivers are likely to be more effective than business as usual.",,"['Pike, Jamison', 'Bogich, Tiffany', 'Elwood, Sarah', 'Finnoff, David C.', 'Daszak, Peter']",,,,
,PMC,Reversal of IgM deficiency following a gluten-free diet in seronegative celiac disease,http://dx.doi.org/10.3748/wjg.v20.i46.17686,PMC4265634,,,"Selective IgM deficiency (sIGMD) is very rare; it may be associated with celiac disease (CD). We present the case of an 18-year-old man with sIGMD masking seronegative CD. Symptoms included abdominal pain, diarrhea and weight loss. Laboratory tests showed reduced IgM, DQ2-HLA and negative anti-transglutaminase. Villous atrophy and diffuse immature lymphocytes were observed at histology. Tissue transglutaminase mRNA mucosal levels showed a 6-fold increase. The patient was treated with a gluten-free diet (GFD) and six months later the symptoms had disappeared, the villous architecture was restored and mucosal tissue transglutaminase mRNA was comparable to that of healthy subjects. After 1 year of GFD, a complete restoration of normal IgM values was observed and duodenal biopsy showed a reduction of immature lymphocytes and normal appearance of mature immune cells.",,"['Montenegro, Lucia', 'Piscitelli, Domenico', 'Giorgio, Floriana', 'Covelli, Claudia', 'Fiore, Maria Grazia', 'Losurdo, Giuseppe', 'Iannone, Andrea', 'Ierardi, Enzo', 'Di Leo, Alfredo', 'Principi, Mariabeatrice']",,,,
,PMC,Barriers to the use of face protection for standard precautions by health care providers,http://dx.doi.org/10.1016/j.ajic.2014.11.002,PMC4367448,,,Health care providers sometimes choose not to use face protection even when indicated as part of standard precautions. We performed a survey of pediatric health care providers to determine barriers to the routine use of face protection. Lack of availability at the point of care and a perceived lack of need were the most commonly cited issues. Continuing education is needed regarding situations in which face protection is indicated for standard precautions.,,"['Kinlay, Joanne', 'Flaherty, Kathleen', 'Scanlon, Patricia', 'Mehrotra, Preeti', 'Potter-Bynoe, Gail', 'Sandora, Thomas J.']",,,,
,PMC,Reducing Outbreaks: Using International Governmental Risk Pools to Fund Research and Development of Infectious Disease Medicines and Vaccines,,PMC4257034,,,"The deadliest Ebola outbreak the world has ever seen is currently ravaging West Africa, despite the concerted efforts of the World Health Organization and many national governments. The current picture is troubling, but not altogether unexpected. Ebola was initially identified in 1976, and since that time, few drugs have been developed to combat it. The same is true for myriad other dangerous infectious diseases to which the world is currently susceptible. One proposal that might prevent outbreaks of this scale and magnitude from recurring would be to have the World Health Organization (WHO) and its technical partners assess which of its member states are at high risk for a disease, either directly or indirectly, and facilitate the creation of international governmental risk pools of those member states. Risk pools would offer open-indexed grant contracts to fund vaccine and drug development for a particular disease, and pharmaceutical companies could browse the index to apply for these grants. If the risk-pool states and a particular company sign a contract, a mutually agreed upon amount of the vaccine or drug would be produced at a below-market purchase price for those states. In return, the company would keep any patents or intellectual property rights for the developed vaccines or drugs. Risk-pool countries that did not use their vaccine or drug could resell that supply on secondary markets to other countries outside of the risk pool. This arrangement will increase the supply of tested drug and vaccine candidates available for combatting unexpected outbreaks of any previously discovered major infectious disease in the future.",,"Erfe, J. Mark",,,,
,PMC,Comparing viral metagenomics methods using a highly multiplexed human viral pathogens reagent,http://dx.doi.org/10.1016/j.jviromet.2014.12.002,PMC4344864,,,"Unbiased metagenomic sequencing holds significant potential as a diagnostic tool for the simultaneous detection of any previously genetically described viral nucleic acids in clinical samples. Viral genome sequences can also inform on likely phenotypes including drug susceptibility or neutralization serotypes. In this study, different variables of the laboratory methods often used to generate viral metagenomics libraries on the efficiency of viral detection and virus genome coverage were compared. A biological reagent consisting of 25 different human RNA and DNA viral pathogens was used to estimate the effect of filtration and nuclease digestion, DNA/RNA extraction methods, pre-amplification and the use of different library preparation kits on the detection of viral nucleic acids. Filtration and nuclease treatment led to slight decreases in the percentage of viral sequence reads and number of viruses detected. For nucleic acid extractions silica spin columns improved viral sequence recovery relative to magnetic beads and Trizol extraction. Pre-amplification using random RT-PCR while generating more viral sequence reads resulted in detection of fewer viruses, more overlapping sequences, and lower genome coverage. The ScriptSeq library preparation method retrieved more viruses and a greater fraction of their genomes than the TruSeq and Nextera methods. Viral metagenomics sequencing was able to simultaneously detect up to 22 different viruses in the biological reagent analyzed including all those detected by qPCR. Further optimization will be required for the detection of viruses in biologically more complex samples such as tissues, blood, or feces.",,"['Li, Linlin', 'Deng, Xutao', 'Mee, Edward T.', 'Collot-Teixeira, Sophie', 'Anderson, Rob', 'Schepelmann, Silke', 'Minor, Philip D.', 'Delwart, Eric']",,,,
,PMC,Anti-Cytomegalovirus Activity of the Anthraquinone Atanyl Blue PRL,http://dx.doi.org/10.1016/j.antiviral.2014.12.003,PMC4289655,,,"Human cytomegalovirus (CMV) causes significant disease in immunocompromised patients and serious birth defects if acquired in utero. Available CMV antivirals target the viral DNA polymerase, have significant toxicities, and suffer from resistance. New drugs targeting different pathways would be beneficial. The anthraquinone emodin is proposed to inhibit herpes simplex virus by blocking the viral nuclease. Emodin and related anthraquinones are also reported to inhibit CMV. In the present study, emodin reduced CMV infectious yield with an EC(50) of 4.9 μM but was cytotoxic at concentrations only two-fold higher. Related anthraquinones acid blue 40 and alizarin violet R inhibited CMV at only high concentrations (238–265 μM) that were also cytotoxic. However, atanyl blue PRL inhibited infectious yield of CMV with an EC(50) of 6.3 μM, significantly below its 50% cytotoxic concentration of 216 μM. Atanyl blue PRL reduced CMV infectivity and inhibited spread. When added up to one h after infection, it dramatically reduced CMV immediate early protein expression and blocked viral DNA synthesis. However, it had no antiviral activity when added 24 h after infection. Interestingly, atanyl blue PRL inhibited nuclease activities of purified CMV UL98 protein with IC(50) of 4.5 and 9.3 μM. These results indicate that atanyl blue PRL targets very early post-entry events in CMV replication and suggest it may act through inhibition of UL98, making it a novel CMV inhibitor. This compound may provide valuable insights into molecular events that occur at the earliest times post-infection and serve as a lead structure for antiviral development.",,"['Alam, Zohaib', 'Al-Mahdi, Zainab', 'Zhu, Yali', 'McKee, Zachary', 'Parris, Deborah S.', 'Parikh, Hardik I.', 'Kellogg, Glen E.', 'Kuchta, Alison', 'McVoy, Michael A.']",,,,
,PMC,p53 Degradation by a Coronavirus Papain-like Protease Suppresses Type I Interferon Signaling,http://dx.doi.org/10.1074/jbc.M114.619890,PMC4317044,,,"Infection by human coronaviruses is usually characterized by rampant viral replication and severe immunopathology in host cells. Recently, the coronavirus papain-like proteases (PLPs) have been identified as suppressors of the innate immune response. However, the molecular mechanism of this inhibition remains unclear. Here, we provide evidence that PLP2, a catalytic domain of the nonstructural protein 3 of human coronavirus NL63 (HCoV-NL63), deubiquitinates and stabilizes the cellular oncoprotein MDM2 and induces the proteasomal degradation of p53. Meanwhile, we identify IRF7 (interferon regulatory factor 7) as a bona fide target gene of p53 to mediate the p53-directed production of type I interferon and the innate immune response. By promoting p53 degradation, PLP2 inhibits the p53-mediated antiviral response and apoptosis to ensure viral growth in infected cells. Thus, our study reveals that coronavirus engages PLPs to escape from the innate antiviral response of the host by inhibiting p53-IRF7-IFNβ signaling.",,"['Yuan, Lin', 'Chen, Zhongbin', 'Song, Shanshan', 'Wang, Shan', 'Tian, Chunyan', 'Xing, Guichun', 'Chen, Xiaojuan', 'Xiao, Zhi-Xiong', 'He, Fuchu', 'Zhang, Lingqiang']",,,,
,PMC,"Examining the policies and guidelines around the use of masks and respirators by healthcare workers in China, Pakistan and Vietnam",http://dx.doi.org/10.1177/1757177414560251,PMC5074170,,,"BACKGROUND: There is an ongoing debate regarding the type of respiratory protection that should be recommended for use for healthcare workers. MATERIALS AND METHODS: A cross-sectional survey was conducted in three countries: China, Pakistan and Vietnam. RESULTS: In China and Pakistan, the infection control guidelines were developed to be in line with the recommendations from the World Health Organization (WHO) and the Centers for Disease Control and Prevention, while in the Vietnamese guidelines the recommendations correspond with the WHO suggestions only. The guidelines from all three countries document the need for training and fit testing; however there is no system to monitor the training and fit testing programs. Across the three countries, there was some inconsistency with regard to the types of products (i.e. masks vs. respirators) recommended for influenza, severe acute respiratory syndrome (SARS) and tuberculosis. CONCLUSIONS: Available evidence should be examined and a comprehensive policy should be developed on the use of masks and respirators. The policy should address critical areas such as regulation, training, fit testing and reuse.",,"['Chughtai, Abrar Ahmad', 'MacIntyre, C Raina', 'Zheng, Yang', 'Wang, Quanyi', 'Toor, Zafar Iqbal', 'Dung, Tham Chi', 'Hien, Nguyen Tran', 'Seale, Holly']",,,,
,PMC,Hepatitis B Virus Polymerase Disrupts K63-Linked Ubiquitination of STING To Block Innate Cytosolic DNA-Sensing Pathways,http://dx.doi.org/10.1128/JVI.02760-14,PMC4338878,,,"The cellular innate immune system recognizing pathogen infection is essential for host defense against viruses. In parallel, viruses have developed a variety of strategies to evade the innate immunity. The hepatitis B virus (HBV), a DNA virus that causes chronic hepatitis, has been shown to inhibit RNA helicase RIG-I-mediated interferon (IFN) induction. However, it is still unknown whether HBV could affect the host DNA-sensing pathways. Here we report that in transiently HBV-transfected Huh7 cells, the stably HBV-producing cell line HepAD38, and HBV-infected HepaRG cells and primary human hepatocytes, HBV markedly interfered with IFN-β induction and antiviral immunity mediated by the stimulator of interferon genes (STING), which has been identified as a central factor in foreign DNA recognition and antiviral innate immunity. Screening analysis demonstrated that the viral polymerase (Pol), but not other HBV-encoded proteins, was able to inhibit STING-stimulated interferon regulatory factor 3 (IRF3) activation and IFN-β induction. Moreover, the reverse transcriptase (RT) and the RNase H (RH) domains of Pol were identified to be responsible for the inhibitory effects. Furthermore, Pol was shown to physically associate with STING and dramatically decrease the K63-linked polyubiquitination of STING via its RT domain without altering the expression level of STING. Taken together, these observations suggest that besides its inherent catalytic function, Pol has a role in suppression of IFN-β production by direct interaction with STING and subsequent disruption of its K63-linked ubiquitination, providing a new mechanism for HBV to counteract the innate DNA-sensing pathways. IMPORTANCE Although whether and how HBV infection induces the innate immune responses are still controversial, it has become increasingly clear that HBV has developed strategies to counteract the pattern recognition receptor-mediated signaling pathways. Previous studies have shown that type I IFN induction activated by the host RNA sensors could be inhibited by HBV. However, it remains unknown whether HBV as a DNA virus utilizes evasion mechanisms against foreign DNA-elicited antiviral signaling. In recent years, the cytosolic DNA sensor and key adaptor STING has been demonstrated to be essential in multiple foreign DNA-elicited innate immune signalings. Here, for the first time, we report STING as a new target of HBV to antagonize IFN induction and identify the viral polymerase responsible for the inhibitory effect, thus providing an additional molecular mechanism by which HBV evades the innate immunity; this implies that in addition to its inherent catalytic function, HBV polymerase is a multifunctional immunomodulatory protein.",,"['Liu, Yinghui', 'Li, Jianhua', 'Chen, Jieliang', 'Li, Yaming', 'Wang, Weixia', 'Du, Xiaoting', 'Song, Wuhui', 'Zhang, Wen', 'Lin, Li', 'Yuan, Zhenghong']",,,,
,PMC,Meeting Report VLPNPV: Sessions 1 and 2: Plenary,http://dx.doi.org/10.4161/21645515.2014.988552,PMC5443086,,,"Following the highly successful inaugural meeting in 2012, the second instalment of Virus-Like Particles and Nano-Particle Vaccines (VLPNPV), proved to be a worthy follow-up in an outstanding conference series. VLPNPV is a forum for academics and industry to address one of the major areas of need in biomedical sciences, the development of novel prophylactic and therapeutic vaccines. The conference was opened by Professor Marianne Manchester of the University of California, San Diego who pointed to the significance of the site chosen for the conference, the Salk Institute. Founded by Jonas Salk, the Salk Institute for Biological Studies is a non-profit, independent research institute with focuses in molecular biology and genetics, neurosciences, and plant biology. This diversity in research themes reflects the wishes of the institute's founder who saw value in using interdisciplinary approaches to understanding the basic principles in life, aimed at generating new therapies and treatments for human disease. Likewise, interdisciplinarity was reflected in the main themes of the meeting, which also highlight some of the potential advantages of virus-like particle (VLP) and nanoparticle vaccines, including novel formulations/adjuvanting effects, structurally accurate/designed antigens, production systems and capacity, and tailoring the immune response. These themes were covered by the 2 plenary sessions that opened the conference and are described in this report.",,"Sainsbury, Frank",,,,
,PMC,Identification of Aim2 as a sensor for DNA vaccines (),http://dx.doi.org/10.4049/jimmunol.1402530,PMC4282968,,,"Recent human study data has re-established the value of DNA vaccines, especially in priming high-level antigen-specific antibody responses, but also raised questions about the mechanisms responsible for such effects. Whereas previous reports have shown involvement of downstream signaling molecules in the innate immune system, the current study investigated the role of Aim2 as a sensor for DNA vaccines. The Aim2 inflammasome directs maturation of the pro-inflammatory cytokines IL-1β and IL-18 and an inflammatory form of cell death called pyroptosis. Both the humoral and cellular antigen-specific adaptive responses were significantly reduced in Aim2(−/−) mice in an IL-1β/IL-18 independent manner after DNA vaccination. Surprisingly, Aim2(−/−) mice also exhibited significantly lower levels of IFN-α/β at the site of injection. These results indicate a previously unreported link between DNA vaccine induced pyroptotic cell death and vaccine immunogenicity that is instrumental in shaping the antigen specific immune response to DNA vaccines.",,"['Suschak, John J.', 'Wang, Shixia', 'Fitzgerald, Katherine A.', 'Lu, Shan']",,,,
,PMC,Population viscosity suppresses disease emergence by preserving local herd immunity,http://dx.doi.org/10.1098/rspb.2014.1901,PMC4213653,,,"Animal reservoirs for infectious diseases pose ongoing risks to human populations. In this theory of zoonoses, the introduction event that starts an epidemic is assumed to be independent of all preceding events. However, introductions are often concentrated in communities that bridge the ecological interfaces between reservoirs and the general population. In this paper, we explore how the risks of disease emergence are altered by the aggregation of introduction events within bridge communities. In viscous bridge communities, repeated introductions can elevate the local prevalence of immunity. This local herd immunity can form a barrier reducing the opportunities for disease emergence. In some situations, reducing exposure rates counterintuitively increases the emergence hazards because of off-setting reductions in local immunity. Increases in population mixing can also increase emergence hazards, even when average contact rates are conserved. Our theory of bridge communities may help guide prevention and explain historical emergence events, where disruption of stable economic, political or demographic processes reduced population viscosity at ecological interfaces.",,"['Reluga, Timothy C.', 'Shim, Eunha']",,,,
,PMC,Comparative experimental subcutaneous glanders and melioidosis in the common marmoset (Callithrix jacchus),http://dx.doi.org/10.1111/iep.12105,PMC4285464,,,"Glanders and melioidosis are caused by two distinct Burkholderia species and have generally been considered to have similar disease progression. While both of these pathogens are HHS/CDC Tier 1 agents, natural infection with both these pathogens is primarily through skin inoculation. The common marmoset (Callithrix jacchus) was used to compare disease following experimental subcutaneous challenge. Acute, lethal disease was observed in marmosets following challenge with between 26 and 1.2 × 10(8) cfu Burkholderia pseudomallei within 22–85 h. The reproducibility and progression of the disease were assessed following a challenge of 1 × 10(2) cfu of B. pseudomallei. Melioidosis was characterised by high levels of bacteraemia, focal microgranuloma progressing to non-necrotic multifocal solid lesions in the livers and spleens and multi-organ failure. Lethal disease was observed in 93% of animals challenged with Burkholderia mallei, occurring between 5 and 10.6 days. Following challenge with 1 × 10(2) cfu of B. mallei, glanders was characterised with lymphatic spread of the bacteria and non-necrotic, multifocal solid lesions progressing to a multifocal lesion with severe necrosis and pneumonia. The experimental results confirmed that the disease pathology and presentation is strikingly different between the two pathogens. The marmoset provides a model of the human syndrome for both diseases facilitating the development of medical countermeasures.",,"['Nelson, Michelle', 'Salguero, Francisco J', 'Dean, Rachel E', 'Ngugi, Sarah A', 'Smither, Sophie J', 'Atkins, Timothy P', 'Lever, Mark S']",,,,
,PMC,Controlled viral glycoprotein expression as a safety feature in a bivalent rabies-ebola vaccine,http://dx.doi.org/10.1016/j.virusres.2014.11.028,PMC4362543,,,,,"['Papaneri, Amy', 'Bernbaum, John', 'Blaney, Joseph E', 'Jahrling, Peter B', 'Schnell, Matthias', 'Johnson, Reed F.']",,,,
,PMC,Mutations across Murine Hepatitis Virus nsp4 Alter Virus Fitness and Membrane Modifications,http://dx.doi.org/10.1128/JVI.02776-14,PMC4338892,,,"A common feature of infection by positive-sense RNA virus is the modification of host cell cytoplasmic membranes that serve as sites of viral RNA synthesis. Coronaviruses induce double-membrane vesicles (DMVs), but the role of DMVs in replication and virus fitness remains unclear. Coronaviruses encode 16 nonstructural proteins (nsps), three of which, nsp3, nsp4, and nsp6, are necessary and sufficient for DMV formation. It has been shown previously that mutations in murine hepatitis virus (MHV) nsp4 loop 1 that alter nsp4 glycosylation are associated with disrupted DMV formation and result in changes in virus replication and RNA synthesis. However, it is not known whether DMV morphology or another function of nsp4 glycosylation is responsible for effects on virus replication. In this study, we tested whether mutations across nsp4, both alone and in combination with mutations that abolish nsp4 glycosylation, affected DMV formation, replication, and fitness. Residues in nsp4 distinct from glycosylation sites, particularly in the endoplasmic reticulum (ER) luminal loop 1, independently disrupted both the number and morphology of DMVs and exacerbated DMV changes associated with loss of glycosylation. Mutations that altered DMV morphology but not glycosylation did not affect virus fitness while viruses lacking nsp4 glycosylation exhibited a loss in fitness. The results support the hypothesis that DMV morphology and numbers are not key determinants of virus fitness. The results also suggest that nsp4 glycosylation serves roles in replication in addition to the organization and stability of MHV-induced double-membrane vesicles. IMPORTANCE All positive-sense RNA viruses modify host cytoplasmic membranes for viral replication complex formation. Thus, defining the mechanisms of virus-induced membrane modifications is essential for both understanding virus replication and development of novel approaches to virus inhibition. Coronavirus-induced membrane changes include double-membrane vesicles (DMVs) and convoluted membranes. Three viral nonstructural proteins (nsps), nsp3, nsp4, and nsp6, are known to be required for DMV formation. It is unknown how these proteins induce membrane modification or which regions of the proteins are involved in DMV formation and stability. In this study, we show that mutations across nsp4 delay virus replication and disrupt DMV formation and that loss of nsp4 glycosylation is associated with a substantial fitness cost. These results support a critical role for nsp4 in DMV formation and virus fitness.",,"['Beachboard, Dia C.', 'Anderson-Daniels, Jordan M.', 'Denison, Mark R.']",,,,
,PMC,Structural Flexibility of a Conserved Antigenic Region in Hepatitis C Virus Glycoprotein E2 Recognized by Broadly Neutralizing Antibodies,http://dx.doi.org/10.1128/JVI.02190-14,PMC4338873,,,"Neutralizing antibodies (NAbs) targeting glycoprotein E2 are important for the control of hepatitis C virus (HCV) infection. One conserved antigenic site (amino acids 412 to 423) is disordered in the reported E2 structure, but a synthetic peptide mimicking this site forms a β-hairpin in complex with three independent NAbs. Our structure of the same peptide in complex with NAb 3/11 demonstrates a strikingly different extended conformation. We also show that residues 412 to 423 are essential for virus entry but not for E2 folding. Together with the neutralizing capacity of the 3/11 Fab fragment, this indicates an unexpected structural flexibility within this epitope. NAbs 3/11 and AP33 (recognizing the extended and β-hairpin conformations, respectively) display similar neutralizing activities despite converse binding kinetics. Our results suggest that HCV utilizes conformational flexibility as an immune evasion strategy, contributing to the limited immunogenicity of this epitope in patients, similar to the conformational flexibility described for other enveloped and nonenveloped viruses. IMPORTANCE Approximately 180 million people worldwide are infected with hepatitis C virus (HCV), and neutralizing antibodies play an important role in controlling the replication of this major human pathogen. We show here that one of the most conserved antigenic sites within the major glycoprotein E2 (amino acids 412 to 423), which is disordered in the recently reported crystal structure of an E2 core fragment, can adopt different conformations in the context of the infectious virus particle. Recombinant Fab fragments recognizing different conformations of this antigenic site have similar neutralization activities in spite of converse kinetic binding parameters. Of note, an antibody response targeting this antigenic region is less frequent than those targeting other more immunogenic regions in E2. Our results suggest that the observed conformational flexibility in this conserved antigenic region contributes to the evasion of the humoral host immune response, facilitating chronicity and the viral spread of HCV within an infected individual.",,"['Meola, Annalisa', 'Tarr, Alexander W.', 'England, Patrick', 'Meredith, Luke W.', 'McClure, C. Patrick', 'Foung, Steven K. H.', 'McKeating, Jane A.', 'Ball, Jonathan K.', 'Rey, Felix A.', 'Krey, Thomas']",,,,
,PMC,Cytomegalovirus-mediated activation of pyrimidine biosynthesis drives UDP–sugar synthesis to support viral protein glycosylation,http://dx.doi.org/10.1073/pnas.1415864111,PMC4273352,,,"Human cytomegalovirus (HCMV) induces numerous changes to the host metabolic network that are critical for high-titer viral replication. We find that HCMV infection substantially induces de novo pyrimidine biosynthetic flux. This activation is important for HCMV replication because inhibition of pyrimidine biosynthetic enzymes substantially decreases the production of infectious virus, which can be rescued through medium supplementation with pyrimidine biosynthetic intermediates. Metabolomic analysis revealed that pyrimidine biosynthetic inhibition considerably reduces the levels of various UDP–sugar metabolites in HCMV-infected, but not mock-infected, cells. Further, UDP–sugar biosynthesis, which provides the sugar substrates required for glycosylation reactions, was found to be induced during HCMV infection. Pyrimidine biosynthetic inhibition also attenuated the glycosylation of the envelope glycoprotein B (gB). Both glycosylation of gB and viral growth were restored by medium supplementation with either UDP–sugar metabolites or pyrimidine precursors. These results indicate that HCMV drives de novo-synthesized pyrimidines to UDP–sugar biosynthesis to support virion protein glycosylation. The importance of this link between pyrimidine biosynthesis and UDP–sugars appears to be partially shared among diverse virus families, because UDP–sugar metabolites rescued the growth attenuation associated with pyrimidine biosynthetic inhibition during influenza A and vesicular stomatitis virus infection, but not murine hepatitis virus infection. In total, our results indicate that viruses can specifically modulate pyrimidine metabolic flux to provide the glycosyl subunits required for protein glycosylation and production of high titers of infectious progeny.",,"['DeVito, Stefanie Renee', 'Ortiz-Riaño, Emilio', 'Martínez-Sobrido, Luis', 'Munger, Joshua']",,,,
,PMC,"Isolation, Characterization, and Functional Analysis of Ferret Lymphatic Endothelial Cells",http://dx.doi.org/10.1016/j.vetimm.2014.11.013,PMC4323863,,,"The lymphatic endothelium (LE) serves as a conduit for transport of immune cells and soluble antigens from peripheral tissues to draining lymph nodes (LNs), contributing to development of host immune responses and possibly dissemination of microbes. Lymphatic endothelial cells (LECs) are major constituents of the lymphatic endothelium. These specialized cells could play important roles in initiation of host innate immune responses through sensing of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs), including toll-like receptors (TLRs). LECs secrete pro-inflammatory cytokines and chemokines to create local inflammatory conditions for recruitment of naïve antigen presenting cells (APCs) such as dendritic cells (DCs) to sites of infection and/or vaccine administration. In this study, we examined the innate immune potential of primary LEC populations derived from multiple tissues of an animal model for human infectious diseases -- the ferret. We generated a total of six primary LEC populations from lung, tracheal, and mesenteric LN tissues from three different ferrets. Standard RT-PCR characterization of these primary LECs showed that they varied in their expression of LEC markers. The ferret LECs were examined for their ability to respond to poly I:C (TLR3 and RIG-1 ligand) and other known TLR ligands as measured by production of proinflammatory cytokine (IFNα, IL6, IL10, Mx1, and TNFα) and chemokine (CCL5, CCL20, and CXCL10) mRNAs using real time RT-PCR. Poly I:C exposure induced robust proinflammatory responses by all of the primary ferret LECs. Chemotaxis was performed to determine the functional activity of CCL20 produced by the primary lung LECs and showed that the LEC-derived CCL20 was abundant and functional. Taken together, our results continue to reveal the innate immune potential of primary LECs during pathogen-host interactions and expand our understanding of the roles of LECs might play in health and disease in animal models.",,"['Berendam, Stella J.', 'Fallert-Junecko, Beth A.', 'Murphy-Corb, Michael A.', 'Fuller, Deborah H.', 'Reinhart, Todd A.']",,,,
,PMC,Mapping Rwanda public health research (1975–2014),http://dx.doi.org/10.4314/ahs.v14i4.41,PMC4370091,,,"BACKGROUND: Since the genocide occurred in 1994, Rwanda has faced up to the challenge of rebuilding. Public health is a main field to understand this rebuilding. OBJECTIVES: In this paper, the aim was to map the scientific research on public health in Rwanda after the genocide and to present the links between different financing systems. METHODS: We used bibliographic analyses with Web of Science of papers published during the period 1975–2014. We performed analyses on journals, most cited articles, authors, publication years, organizations, funding companies, countries, and keywords. RESULTS: We obtained 86 articles between 1975 and 2014. Most articles were published after 2007. The main countries of research laboratories were the United States of America, Rwanda, England and Belgium and represented the main network collaboration. The relevant keywords were: HIV, woman, child, program, rural and violence. CONCLUSIONS: Public health research on Rwanda appeared 14 years after the genocide. A main field was emerging: the spread of HIV with mother-child transmission, and the policies to take this subject into account in rural zones. The network of institutions developing these studies was USA-Rwanda.",,"Poreau, Brice",,,,
,PMC,Absolute Humidity Influences the Seasonal Persistence and Infectivity of Human Norovirus,http://dx.doi.org/10.1128/AEM.01871-14,PMC4249182,,,"Norovirus (NoV) is one of the main causative agents of acute gastroenteritis worldwide. In temperate climates, outbreaks peak during the winter season. The mechanism by which climatic factors influence the occurrence of NoV outbreaks is unknown. We hypothesized that humidity is linked to NoV seasonality. Human NoV is not cultivatable, so we used cultivatable murine norovirus (MNV) as a surrogate to study its persistence when exposed to various levels of relative humidity (RH) from low (10% RH) to saturated (100% RH) conditions at 9 and 25°C. In addition, we conducted similar experiments with virus-like particles (VLPs) from the predominant GII-4 norovirus and studied changes in binding patterns to A, B, and O group carbohydrates that might reflect capsid alterations. The responses of MNV and VLP to humidity were somewhat similar, with 10 and 100% RH exhibiting a strong conserving effect for both models, whereas 50% RH was detrimental for MNV infectivity and VLP binding capacity. The data analysis suggested that absolute humidity (AH) rather than RH is the critical factor for keeping NoV infectious, with an AH below 0.007 kg water/kg air being favorable to NoV survival. Retrospective surveys of the meteorological data in Paris for the last 14 years showed that AH average values have almost always been below 0.007 kg water/kg air during the winter (i.e., 0.0046 ± 0.0014 kg water/kg air), and this finding supports the fact that low AH provides an ideal condition for NoV persistence and transmission during cold months.",,"['Colas de la Noue, Alexandre', 'Estienney, Marie', 'Aho, Serge', 'Perrier-Cornet, Jean-Marie', 'de Rougemont, Alexis', 'Pothier, Pierre', 'Gervais, Patrick', 'Belliot, Gaël']",,,,
,PMC,The Changing Face of Crises and Aid in the Asia-Pacific,http://dx.doi.org/10.1089/bsp.2014.0025,PMC4248250,,,"Both US foreign policy and global attention attest to the strategic, economic, and political importance of Asia. Yet, the region faces urgent challenges that must be addressed if it is to remain stable and prosperous. The densely populated countries of the Asia-Pacific are beleaguered by poverty, population displacement, decreasing access to potable water and adequate sanitation, and high rates of disease morbidity and mortality. New and reemerging diseases known to have originated in Asia over the past decades have spread globally by international trade, tourism, worker migration, and agricultural exportation. Unremitting naturally occurring and man-made disasters have strained Southeast Asia's already fragile disaster and public health response infrastructures and the essential services they provide (eg, surveillance, vaccination, maternal and child health, and mental health programs). Following disasters, governments often contract with the broader humanitarian community (eg, indigenous and international NGOs) and seek the assistance of militaries to provide essential services. Yet, their roles and capabilities in addressing acute and chronic health issues in the wake of complex disasters remain unclear. Current mechanisms of nation-state and outside organization interaction, including dissimilar operational platforms, may limit true partnership on behalf of the health security mission. Additionally, concerns regarding skill sets and the lack of standards-based training raise questions about the balance between developing internal response capabilities and professionalizing external, deployable resources. Both the mega-disasters that are forecast for the region and the global health security threats that are expected to emanate from them require an increased focus on improving the Asia-Pacific's emergency preparedness and response posture.",,"['Gursky, Elin A.', 'Burkle, Frederick M.', 'Hamon, David W.', 'Walker, Peter', 'Benjamin, Georges C.']",,,,
,PMC,Inhibition of priming for bovine respiratory syncytial virus-specific protective immune responses following parenteral vaccination of passively immune calves,,PMC4231808,,,"The effect of maternal antibodies (MatAb) on immunological priming by neonatal parenteral vaccination for bovine respiratory syncytial virus (BRSV) was addressed for the first time in experimental infection in 34 Holstein calves. Both vaccinated and control calves developed moderate to severe respiratory disease characteristic of acute BRSV infection. There were no differences in clinical signs, BRSV shed, arterial oxygen concentrations, or mortality between vaccinated and control calves after BRSV challenge approximately 11 wk after vaccination. There were no anamnestic antibody or cytokine responses in the vaccinates after challenge. Lung lesions were extensive in both groups, and although there was a statistically significant (P = 0.05) difference between groups, this difference was considered not biologically significant. These data indicate that stimulation of protective immune responses was inhibited by maternal antibodies when a combination modified-live BRSV vaccine was administered parenterally to young passively immune calves. Alternate routes of administration or different vaccine formulations should be used to successfully immunize young calves with good passive antibody transfer.",,"['Ellis, John', 'Gow, Sheryl', 'Bolton, Michael', 'Burdett, William', 'Nordstrom, Scott']",,,,
,PMC,"Comparison of the IMDx Influenza A Virus, Influenza B Virus, and Respiratory Syncytial Virus A/B Assay on the m2000 Platform with Real-Time Reverse Transcriptase PCR Assays",http://dx.doi.org/10.1128/JCM.02565-14,PMC4313329,,,,,"['Adachi, Dena', 'Tang, Julian W.', 'Lundeberg, Roberta', 'Tipples, Graham', 'Charlton, Carmen L.', 'Drews, Steven J.']",,,,
,PMC,A Highly Sensitive Europium Nanoparticle-Based Immunoassay for Detection of Influenza A/B Virus Antigen in Clinical Specimens,http://dx.doi.org/10.1128/JCM.02635-14,PMC4313323,,,We report the development of a novel europium nanoparticle-based immunoassay (ENIA) for rapid detection of influenza A and influenza B viruses. The ENIA demonstrated sensitivities of 90.7% (147/162) for influenza A viruses and 81.80% (9/11) for influenza B viruses compared to those for an in-house reverse transcription (RT)-PCR assay in testing of influenza-positive clinical samples.,,"['Zhang, Panhe', 'Vemula, Sai Vikram', 'Zhao, Jiangqin', 'Du, Bingchen', 'Mohan, Haleyurgirisetty', 'Liu, Jikun', 'El Mubarak, Haja Sittana', 'Landry, Marie L.', 'Hewlett, Indira']",,,,
,PMC,Genotypic Characterization of Canine Coronaviruses Associated with Fatal Canine Neonatal Enteritis in the United States,http://dx.doi.org/10.1128/JCM.02158-14,PMC4313292,,,"Emerging canine coronavirus (CCoV) variants that are associated with systemic infections have been reported in the European Union; however, CCoV-associated disease in the United States is incompletely characterized. The purpose of this study was to correlate the clinicopathological findings and viral antigen distribution with the genotypic characteristics of CCoV in 11 puppies from nine premises in five states that were submitted for diagnostic investigation at Cornell University between 2008 and 2013. CCoV antigen was found in epithelial cells of small intestinal villi in all puppies and the colon in 2 of the 10 puppies where colon specimens were available. No evidence of systemic CCoV infection was found. Comparative sequence analyses of viral RNA extracted from intestinal tissues revealed CCoV-II genotype in 9 out of 11 puppies. Of the nine CCoV-IIs, five were subtyped as group IIa and one as IIb, while three CCoVs could not be subtyped. One of the CCoV-IIa variants was isolated in cell culture. Infection with CCoV alone was found in five puppies, of which two also had small intestinal intussusception. Concurrent infections with either parvovirus (n = 1), attaching-effacing Escherichia coli (n = 4), or protozoan parasites (n = 3) were found in the other six puppies. CCoV is an important differential diagnosis in outbreaks of severe enterocolitis among puppies between 4 days and 21 weeks of age that are housed at high population density. These findings will assist with the rapid laboratory diagnosis of enteritis in puppies and highlight the need for continued surveillance for CCoV variants and intestinal viral diseases of global significance.",,"['Licitra, Beth N.', 'Whittaker, Gary R.', 'Dubovi, Edward J.', 'Duhamel, Gerald E.']",,,,
,PMC,RNA Populations in Immunocompromised Patients as Reservoirs for Novel Norovirus Variants,http://dx.doi.org/10.1128/JVI.02494-14,PMC4249157,,,"Noroviruses are the leading cause of acute gastroenteritis outbreaks worldwide. The majority of norovirus outbreaks are caused by genogroup II.4 (GII.4). Novel GII.4 strains emerge every 2 to 4 years and replace older variants as the dominant norovirus. Novel variants emerge through a combination of recombination, genetic drift, and selection driven by population immunity, but the exact mechanism of how or where is not known. We detected two previously unknown novel GII.4 variants, termed GII.4 UNK1 and GII.4 UNK2, and a diverse norovirus population in fecal specimens from immunocompromised individuals with diarrhea after they had undergone bone marrow transplantation. We hypothesized that immunocompromised individuals can serve as reservoirs for novel norovirus variants. To test our hypothesis, metagenomic analysis of viral RNA populations was combined with a full-genome bioinformatic analysis of publicly available GII.4 norovirus sequences from 1974 to 2014 to identify converging sites. Variable sites were proportionally more likely to be within two amino acids (P < 0.05) of positively selected sites. Further analysis using a hypergeometric distribution indicated that polymorphic site distribution was random and its proximity to positively selected sites was dependent on the size of the norovirus genome and the number of positively selected sites.In conclusion, random mutations may have a positive impact on driving norovirus evolution, and immunocompromised individuals could serve as potential reservoirs for novel GII.4 strains. IMPORTANCE Norovirus is the most common cause of viral gastroenteritis in the United States. Every 2 to 3 years novel norovirus variants emerge and replace dominant strains. The continual emergence of novel noroviruses is believed to be caused by a combination of genetic drift, population immunity, and recombination, but exactly how this emergence occurs remains unknown. In this study, we identified two novel GII.4 variants in immunocompromised bone marrow transplant patients. Using metagenomic and bioinformatic analysis, we showed that most genetic polymorphisms in the novel variants occur near 0 to 2 amino acids of positively selected sites, but the distribution of mutations was random; clustering of polymorphisms with positively selected sites was a result of genome size and number of mutations and positively selected sites. This study shows that immunocompromised patients can harbor infectious novel norovirus variants, and although mutations in viruses are random, they can have a positive effect on viral evolution.",,"['Vega, Everardo', 'Donaldson, Eric', 'Huynh, Jeremy', 'Barclay, Leslie', 'Lopman, Ben', 'Baric, Ralph', 'Chen, Luke F.', 'Vinjé, Jan']",,,,
,PMC,Suppressors of Cytokine Signaling 1 and 3 Are Upregulated in Brain Resident Cells in Response to Virus-Induced Inflammation of the Central Nervous System via at Least Two Distinctive Pathways,http://dx.doi.org/10.1128/JVI.01346-14,PMC4249144,,,"Suppressors of cytokine signaling (SOCS) proteins are intracellular proteins that inhibit cytokine signaling in a variety of cell types. A number of viral infections have been associated with SOCS upregulation; however, not much is known about the mechanisms regulating SOCS expression during viral infection. In this study, we used two pathologically distinct intracerebral (i.c.) infection models to characterize temporal and spatial aspects of SOCS expression in the virus-infected central nervous system (CNS), and by employing various knockout mouse models, we sought to identify regulatory mechanisms that may underlie a virus induced upregulation of SOCS in the CNS. We found that i.c. infection with either lymphocytic choriomeningitis virus (LCMV) or yellow fever virus (YF) results in gradual upregulation of SOCS1/3 mRNA expression peaking at day 7 postinfection (p.i.). In the LCMV model, SOCS mRNA was expressed in brain resident cells, including astrocytes and some neurons, and for SOCS1 in particular this upregulation was almost entirely mediated by gamma interferon (IFN-γ) produced by infiltrating T cells. After infection with YF, we also found SOCS expression to be upregulated in brain resident cells with a peak on day 7 p.i., but in this model, the upregulation was only partially dependent on IFN-γ and T cells, indicating that at least one other mediator was involved in the upregulation of SOCS following YF infection. We conclude that virus-induced inflammation of the CNS is associated with upregulation of SOCS1/3 mRNA expression in brain resident cells and that at least two distinctive pathways can lead to this upregulation. IMPORTANCE In the present report, we have studied the induction of SOCS1 and SOCS3 expression in the context of virus-induced CNS infection. We found that both a noncytolytic and a cytolytic virus induce marked upregulation of SOCS1 and -3 expression. Notably, the kinetics of the observed upregulation follows that of activity within proinflammatory signaling pathways and, interestingly, type II interferon (IFN), which is also a key inducer of inflammatory mediators, seems to be essential in initiating this counterinflammatory response. Another key observation is that not only cells of the immune system but also CNS resident cells are actively involved in both the pro- and the counterinflammatory immune circuits; thus, for example, astrocytes upregulate both C-X-C-motif chemokine 10 (CXCL10) and SOCS when exposed to type II IFN in vivo.",,"['Steffensen, Maria Abildgaard', 'Fenger, Christina', 'Christensen, Jeanette Erbo', 'Jørgensen, Carina Krogsgaard', 'Bassi, Maria Rosaria', 'Christensen, Jan Pravsgaard', 'Finsen, Bente', 'Thomsen, Allan Randrup']",,,,
,PMC,"Different Roles of the Three Loops Forming the Adhesive Interface of Nectin-4 in Measles Virus Binding and Cell Entry, Nectin-4 Homodimerization, and Heterodimerization with Nectin-1",http://dx.doi.org/10.1128/JVI.02379-14,PMC4249131,,,"Many viruses utilize cell adhesion molecules of the immunoglobulin superfamily as receptors. In particular, viruses of different classes exploit nectins. The large DNA viruses, herpes simplex and pseudorabies viruses, use ubiquitous nectins 1 and 2. The negative-strand RNA virus measles virus (MeV) uses tissue-specific nectin-4, and the positive-strand RNA virus poliovirus uses nectin-like 5 (necl-5), also known as poliovirus receptor. These viruses contact the BC, C′C″, and FG loops on the upper tip of their receptor's most membrane-distal domain. This location corresponds to the newly defined canonical adhesive interface of nectins, but how viruses utilize this interface has remained unclear. Here we show that the same key residues in the BC and FG loops of nectin-4 govern binding to the MeV attachment protein hemagglutinin (H) and cell entry, nectin-4 homodimerization, and heterodimerization with nectin-1. On the other hand, residues in the C′C″ loop necessary for homo- and heterotypic interactions are dispensable for MeV-induced fusion and cell entry. Remarkably, the C′C″ loop governs dissociation of the nectin-4 and H ectodomains. We provide formal proof that H can interfere with the formation of stable nectin-1/nectin-4 heterodimers. Finally, while developing an alternative model to study MeV spread, we observed that polarized primary pig airway epithelial sheets cannot be infected. We show that a single amino acid variant in the BC loop of pig nectin-4 fully accounts for restricted MeV entry. Thus, the three loops forming the adhesive interface of nectin-4 have different roles in supporting MeV H association and dissociation and MeV-induced fusion. IMPORTANCE Different viruses utilize nectins as receptors. Nectins are immunoglobulin superfamily glycoproteins that mediate cell-cell adhesion in vertebrate tissues. They interact through an adhesive interface located at the top of their membrane-distal domain. How viruses utilize the three loops forming this interface has remained unclear. We demonstrate that while nectin-nectin interactions require residues in all three loops, the association of nectin-4 with the measles virus hemagglutinin requires only the BC and FG loops. However, we discovered that residues in the C′C″ loop modulate the dissociation of nectin-4 from the viral hemagglutinin. Analogous mechanisms may support cell entry of other viruses that utilize nectins or other cell adhesion molecules of the immunoglobulin superfamily as receptors.",,"['Mateo, Mathieu', 'Navaratnarajah, Chanakha K.', 'Willenbring, Robin C.', 'Maroun, Justin W.', 'Iankov, Ianko', 'Lopez, Marc', 'Sinn, Patrick L.', 'Cattaneo, Roberto']",,,,
,PMC,Exposure of Epitope Residues on the Outer Face of the Chikungunya Virus Envelope Trimer Determines Antibody Neutralizing Efficacy,http://dx.doi.org/10.1128/JVI.01943-14,PMC4249124,,,"Chikungunya virus (CHIKV) is a reemerging alphavirus that causes a debilitating arthritic disease and infects millions of people and for which no specific treatment is available. Like many alphaviruses, the structural targets on CHIKV that elicit a protective humoral immune response in humans are poorly defined. Here we used phage display against virus-like particles (VLPs) to isolate seven human monoclonal antibodies (MAbs) against the CHIKV envelope glycoproteins E2 and E1. One MAb, IM-CKV063, was highly neutralizing (50% inhibitory concentration, 7.4 ng/ml), demonstrated high-affinity binding (320 pM), and was capable of therapeutic and prophylactic protection in multiple animal models up to 24 h postexposure. Epitope mapping using a comprehensive shotgun mutagenesis library of 910 mutants with E2/E1 alanine mutations demonstrated that IM-CKV063 binds to an intersubunit conformational epitope on domain A, a functionally important region of E2. MAbs against the highly conserved fusion loop have not previously been reported but were also isolated in our studies. Fusion loop MAbs were broadly cross-reactive against diverse alphaviruses but were nonneutralizing. Fusion loop MAb reactivity was affected by temperature and reactivity conditions, suggesting that the fusion loop is hidden in infectious virions. Visualization of the binding sites of 15 different MAbs on the structure of E2/E1 revealed that all epitopes are located at the membrane-distal region of the E2/E1 spike. Interestingly, epitopes on the exposed topmost and outer surfaces of the E2/E1 trimer structure were neutralizing, whereas epitopes facing the interior of the trimer were not, providing a rationale for vaccine design and therapeutic MAb development using the intact CHIKV E2/E1 trimer. IMPORTANCE CHIKV is the most important alphavirus affecting humans, resulting in a chronic arthritic condition that can persist for months or years. In recent years, millions of people have been infected globally, and the spread of CHIKV to the Americas is now beginning, with over 100,000 cases occurring in the Caribbean within 6 months of its arrival. Our study reports on seven human MAbs against the CHIKV envelope, including a highly protective MAb and rarely isolated fusion loop MAbs. Epitope mapping of these MAbs demonstrates how some E2/E1 epitopes are exposed or hidden from the human immune system and suggests a structural mechanism by which these MAbs protect (or fail to protect) against CHIKV infection. Our results suggest that the membrane-distal end of CHIKV E2/E1 is the primary target for the humoral immune response to CHIKV, and antibodies targeting the exposed topmost and outer surfaces of the E2/E1 trimer determine the neutralizing efficacy of this response.",,"['Fong, Rachel H.', 'Banik, Soma S. R.', 'Mattia, Kimberly', 'Barnes, Trevor', 'Tucker, David', 'Liss, Nathan', 'Lu, Kai', 'Selvarajah, Suganya', 'Srinivasan, Surabhi', 'Mabila, Manu', 'Miller, Adam', 'Muench, Marcus O.', 'Michault, Alain', 'Rucker, Joseph B.', 'Paes, Cheryl', 'Simmons, Graham', 'Kahle, Kristen M.', 'Doranz, Benjamin J.']",,,,
,PMC,Effects of Human Anti-Spike Protein Receptor Binding Domain Antibodies on Severe Acute Respiratory Syndrome Coronavirus Neutralization Escape and Fitness,http://dx.doi.org/10.1128/JVI.02232-14,PMC4248992,,,"The receptor binding domain (RBD) of the spike (S) glycoprotein of severe acute respiratory syndrome coronavirus (SARS-CoV) is a major target of protective immunity in vivo. Although a large number of neutralizing antibodies (nAbs) have been developed, it remains unclear if a single RBD-targeting nAb or two in combination can prevent neutralization escape and, if not, attenuate viral virulence in vivo. In this study, we used a large panel of human nAbs against an epitope that overlaps the interface between the RBD and its receptor, angiotensin-converting enzyme 2 (ACE2), to assess their cross-neutralization activities against a panel of human and zoonotic SARS-CoVs and neutralization escape mutants. We also investigated the neutralization escape profiles of these nAbs and evaluated their effects on receptor binding and virus fitness in vitro and in mice. We found that some nAbs had great potency and breadth in neutralizing multiple viral strains, including neutralization escape viruses derived from other nAbs; however, no single nAb or combination of two blocked neutralization escape. Interestingly, in mice the neutralization escape mutant viruses showed either attenuation (Urbani background) or increased virulence (GD03 background) consistent with the different binding affinities between their RBDs and the mouse ACE2. We conclude that using either single nAbs or dual nAb combinations to target a SARS-CoV RBD epitope that shows plasticity may have limitations for preventing neutralization escape during in vivo immunotherapy. However, RBD-directed nAbs may be useful for providing broad neutralization and prevention of escape variants when combined with other nAbs that target a second conserved epitope with less plasticity and more structural constraint. IMPORTANCE The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 has resulted in severe human respiratory disease with high death rates. Their zoonotic origins highlight the likelihood of reemergence or further evolution into novel human coronavirus pathogens. Broadly neutralizing antibodies (nAbs) that prevent infection of related viruses represent an important immunostrategy for combating coronavirus infections; however, for this strategy to succeed, it is essential to uncover nAb-mediated escape pathways and to pioneer strategies that prevent escape. Here, we used SARS-CoV as a research model and examined the escape pathways of broad nAbs that target the receptor binding domain (RBD) of the virus. We found that neither single nAbs nor two nAbs in combination blocked escape. Our results suggest that targeting conserved regions with less plasticity and more structural constraint rather than the SARS-CoV RBD-like region(s) should have broader utility for antibody-based immunotherapy.",,"['Sui, Jianhua', 'Deming, Meagan', 'Rockx, Barry', 'Liddington, Robert C.', 'Zhu, Quan Karen', 'Baric, Ralph S.', 'Marasco, Wayne A.']",,,,
,PMC,Crystal Structure of Herpes Simplex Virus 2 gD Bound to Nectin-1 Reveals a Conserved Mode of Receptor Recognition,http://dx.doi.org/10.1128/JVI.01906-14,PMC4248990,,,"Herpes simplex virus 1 (HSV-1) and HSV-2 are among the most prevalent human pathogens. Both viruses can recognize, via the surface envelope glycoprotein D (gD), human nectin-1 as a functional receptor. Previous studies have successfully elucidated the molecular basis of the binding between HSV-1 gD and nectin-1 by cocrystallography. Despite a high sequence identity between HSV-1 and HSV-2 gDs, the atomic intermolecule details for the HSV-2-gD/nectin-1 interaction remain elusive. Here, we report the crystal structures of both the unbound and the nectin-1-bound HSV-2 gDs. The free-gD structure expectedly comprises an IgV-like core and the surface-exposed terminal extensions as observed in its HSV-1 counterpart but lacks traceable electron densities for a large portion of the terminal elements. These terminal residues were clearly traced in the complex structure as a definitive loop in the N terminus and an α-helix in the C terminus, thereby showing a conserved nectin-1-binding mode as reported for HSV-1 gD. The interface residues in nectin-1 were further mutated and tested for the gD interaction by surface plasmon resonance. The resultant binding patterns were similar for HSV-1 and HSV-2 gDs, further supporting a homologous receptor-binding basis by the two viruses for nectin-1. These data, together with a cell-based fusion assay showing a cross-inhibition of the gD/nectin-1-mediated cell-cell fusion by soluble HSV-1 and HSV-2 gDs, provided solid structural and functional evidence that HSV-1 and HSV-2 recognize nectin-1 via the same binding mode. Finally, we also demonstrated that nectin-1 I80 is an important residue involved in gD interaction. IMPORTANCE Despite intensified studies, a detailed picture of the molecular features in the HSV-2-gD/nectin-1 interaction remains unavailable. Previous work focused on HSV-1 gD, which folds into an IgV-like core with large terminal extensions and utilizes the extension elements to engage nectin-1. Here, we report the crystal structures of HSV-2 gD in both the free and the nectin-1-bound forms. The atomic intermolecule details for HSV-2-gD/nectin-1 interaction are clearly presented. The observed binding mode is identical to that reported for its HSV-1 counterpart. This structural observation was further supported by our comparative functional assays showing that nectin-1 mutations similarly affect the ligand-receptor interaction of both virus gDs. Taken together, we provide comprehensive structural and functional data demonstrating a conserved receptor-binding mode between HSV-1 and HSV-2 for nectin-1. Our results also indicate that the tropism difference between the two viruses likely arises from aspects other than the gD/nectin-1 binding features.",,"['Lu, Guangwen', 'Zhang, Na', 'Qi, Jianxun', 'Li, Yan', 'Chen, Zhujun', 'Zheng, Chunfu', 'Gao, George F', 'Yan, Jinghua']",,,,
,PMC,Overlapping and Distinct Molecular Determinants Dictating the Antiviral Activities of TRIM56 against Flaviviruses and Coronavirus,http://dx.doi.org/10.1128/JVI.02505-14,PMC4248981,,,"The tripartite motif-containing (TRIM) proteins have emerged as a new class of host antiviral restriction factors, with several demonstrating roles in regulating innate antiviral responses. Of >70 known TRIMs, TRIM56 inhibits replication of bovine viral diarrhea virus, a ruminant pestivirus of the family Flaviviridae, but has no appreciable effect on vesicular stomatitis virus (VSV), a rhabdovirus. Yet the antiviral spectrum of TRIM56 remains undefined. In particular, how TRIM56 impacts human-pathogenic viruses is unknown. Also unclear are the molecular determinants governing the antiviral activities of TRIM56. Herein, we show that TRIM56 poses a barrier to infections by yellow fever virus (YFV), dengue virus serotype 2 (DENV2), and human coronavirus virus (HCoV) OC43 but not encephalomyocarditis virus (EMCV). Moreover, by engineering cell lines conditionally expressing various TRIM56 mutants, we demonstrated that TRIM56's antiflavivirus effects required both the E3 ligase activity that lies in the N-terminal RING domain and the integrity of its C-terminal portion, while the restriction of HCoV-OC43 relied upon the TRIM56 E3 ligase activity alone. Furthermore, TRIM56 was revealed to impair YFV and DENV2 propagation by suppressing intracellular viral RNA accumulation but to compromise HCoV-OC43 infection at a later step in the viral life cycle, suggesting that distinct TRIM56 domains accommodate differing antiviral mechanisms. Altogether, TRIM56 is a versatile antiviral host factor that confers resistance to YFV, DENV2, and HCoV-OC43 through overlapping and distinct molecular determinants. IMPORTANCE We previously reported tripartite motif protein 56 (TRIM56) as a host restriction factor of bovine viral diarrhea virus, a ruminant pathogen. However, the impact of TRIM56 on human-pathogenic RNA viruses is unknown. Herein, we demonstrate that TRIM56 restricts two medically important flaviviruses, yellow fever virus (YFV) and dengue virus serotype 2 (DENV2), and a human coronavirus, HCoV-OC43, but not encephalomyocarditis virus, a picornavirus. Further, we show that TRIM56-mediated inhibition of HCoV-OC43 multiplication depends solely on its E3 ligase activity, whereas its restriction of YFV and DENV2 requires both the E3 ligase activity and integrity of the C-terminal portion. The differing molecular determinants appear to accommodate distinct antiviral mechanisms TRIM56 adopts to target different families of viruses; while TRIM56 curbs intracellular YFV/DENV2 RNA replication, it acts at a later step in HCoV-OC43 life cycle. These novel findings illuminate the molecular basis of the versatility and specificity of TRIM56's antiviral activities against positive-strand RNA viruses.",,"['Liu, Baoming', 'Li, Nan L.', 'Wang, Jie', 'Shi, Pei-Yong', 'Wang, Tianyi', 'Miller, Mark A.', 'Li, Kui']",,,,
,PMC,Sendai Virus Pathogenesis in Mice Is Prevented by Ifit2 and Exacerbated by Interferon,http://dx.doi.org/10.1128/JVI.02201-14,PMC4248979,,,"The type I/III interferon (IFN) system has major roles in regulating viral pathogenesis, usually ameliorating pathogenesis by impairing virus replication through the antiviral actions of one or more IFN-induced proteins. Ifit2 is one such protein which can be induced by IFN or virus infection, and it is responsible for protecting mice from neuropathogenesis caused by vesicular stomatitis virus. Here, we show that Ifit2 also protects mice from pathogenesis caused by the respirovirus Sendai virus (SeV). Mice lacking Ifit2 (Ifit2(−/−)) suffered severe weight loss and succumbed to intranasal infection with SeV strain 52 at a dose that killed only a few wild-type mice. Viral RNA was detectable only in lungs, and SeV titers were higher in Ifit2(−/−) mice than in wild-type mice. Similar infiltration of immune cells was found in the lungs of both mouse lines, corresponding to similar levels of many induced cytokines and chemokines. In contrast, IFN-β and IFN-λ3 expression were considerably higher in the lungs of Ifit2(−/−) mice. Surprisingly, type I IFN receptor knockout (IFNAR(−/−)) mice were less susceptible to SeV than Ifit2(−/−) mice, although their pulmonary virus titers were similarly high. To test the intriguing possibility that type I IFN action enhances pathogenesis in the context of elevated SeV replication in lungs, we generated Ifit2/IFNAR(−/−) double knockout mice. These mice were less susceptible to SeV than Ifit2(−/−) mice, although viral titers in their lungs were even higher. Our results indicate that high SeV replication in the lungs of infected Ifit2(−/−) mice cooperates with elevated IFN-β induction to cause disease. IMPORTANCE The IFN system is an innate defense against virus infections. It is triggered quickly in infected cells, which then secrete IFN. Via their cell surface receptors on surrounding cells, they induce transcription of numerous IFN-stimulated genes (ISG), which in turn protect these cells by inhibiting virus life cycles. Hence, IFNs are commonly considered beneficial during virus infections. Here, we report two key findings. First, lack of a single ISG in mice, Ifit2, resulted in high mortality after SeV infection of the respiratory tract, following higher virus loads and higher IFN production in Ifit2(−/−) lungs. Second, mortality of Ifit2(−/−) mice was reduced when mice also lacked the type I IFN receptor, while SeV loads in lungs still were high. This indicates that type I IFN exacerbates pathogenesis in the SeV model, and that limitation of both viral replication and IFN production is needed for effective prevention of disease.",,"['Wetzel, Jaime L.', 'Fensterl, Volker', 'Sen, Ganes C.']",,,,
,PMC,Characterization of an Alphamesonivirus 3C-Like Protease Defines a Special Group of Nidovirus Main Proteases,http://dx.doi.org/10.1128/JVI.02040-14,PMC4248970,,,"Cavally virus (CavV) and related viruses in the family Mesoniviridae diverged profoundly from other nidovirus lineages but largely retained the characteristic set of replicative enzymes conserved in the Coronaviridae and Roniviridae. The expression of these enzymes in virus-infected cells requires the extensive proteolytic processing of two large replicase polyproteins, pp1a and pp1ab, by the viral 3C-like protease (3CL(pro)). Here, we show that CavV 3CL(pro) autoproteolytic cleavage occurs at two N-terminal (N1 and N2) and one C-terminal (C1) processing site(s). The mature form of 3CL(pro) was revealed to be a 314-residue protein produced by cleavage at FKNK(1386)|SAAS (N2) and YYNQ(1700)|SATI (C1). Site-directed mutagenesis data suggest that the mesonivirus 3CL(pro) employs a catalytic Cys-His dyad comprised of CavV pp1a/pp1ab residues Cys-1539 and His-1434. The study further suggests that mesonivirus 3CL(pro) substrate specificities differ from those of related nidovirus proteases. The presence of Gln (or Glu) at the P1 position was not required for cleavage, although residues that control Gln/Glu specificity in related viral proteases are retained in the CavV 3CL(pro) sequence. Asn at the P2 position was identified as a key determinant for mesonivirus 3CL(pro) substrate specificity. Other positions, including P4 and P1′, each are occupied by structurally related amino acids, indicating a supportive role in substrate binding. Together, the data identify a new subgroup of nidovirus main proteases and support previous conclusions on phylogenetic relationships between the main nidovirus lineages. IMPORTANCE Mesoniviruses have been suggested to provide an evolutionary link between nidovirus lineages with small (13 to 16 kb) and large (26 to 32 kb) RNA genome sizes, and it has been proposed that a specific set of enzymes, including a proofreading exoribonuclease and other replicase gene-encoded proteins, play a key role in the major genome expansion leading to the currently known lineages of large nidoviruses. Despite their smaller genome size (20 kb), mesoniviruses retained most of the replicative domains conserved in large nidoviruses; thus, they are considered interesting models for studying possible key events in the evolution of RNA genomes of exceptional size and complexity. Our study provides the first characterization of a mesonivirus replicase gene-encoded nonstructural protein. The data confirm and extend previous phylogenetic studies of mesoniviruses and related viruses and pave the way for studies into the formation of the mesonivirus replication complex and functional and structural studies of its functional subunits.",,"['Blanck, Sandra', 'Stinn, Anne', 'Tsiklauri, Lali', 'Zirkel, Florian', 'Junglen, Sandra', 'Ziebuhr, John']",,,,
,PMC,Preparedness for Ebola Virus Disease,,PMC4597906,,,,,"['NAGATA, Takashi', 'ISHII, Masami']",,,,
,PMC,Duration of Rhinovirus Shedding in the Upper Respiratory Tract in the First Year of Life,http://dx.doi.org/10.1542/peds.2014-2132,PMC4243071,,,"BACKGROUND: Current molecular diagnostic methods have detected rhinovirus RNA in a high proportion of asymptomatic infants and children, raising the question of the clinical significance of these findings. This study investigates the prevalence of prolonged rhinovirus RNA presence in the upper respiratory tract of infants during the first year of life. METHODS: In a longitudinal study, infants were followed from birth up to 12 months. Nasopharyngeal specimens were collected monthly (months 1–6 and month 9) and during an upper respiratory infection. Rhinoviruses were detected by quantitative reverse-transcription polymerase chain reaction. Presence of repeated rhinovirus RNA was evaluated by nucleotide sequence analysis. RESULTS: A total of 2153 specimens from 362 infants were studied; 341 distinct rhinovirus infections in 216 infants were identified. Follow-up specimens were available within 30 days for 179 infections, creating the sample set to assess prolonged rhinovirus presence. Of the 179 infections, 46 involved the detection of the same rhinovirus strain in repeated specimens, including 8 events of prolonged presence of the same strain (detected in specimens collected >30 days apart), representing 4.5% of the evaluable rhinovirus infections. There were 26 events in which a rhinovirus strain was replaced by a different strain within a 30-day interval, representing 14.5% of the 179 infections. CONCLUSIONS: Although rhinovirus infections are common in healthy infants, prolonged presence of rhinovirus RNA in the respiratory tract after an upper respiratory infection was uncommon (<5%). Detection of rhinovirus RNA in an infant most likely represents an infection within a 30-day period.",,"['Loeffelholz, Michael J.', 'Trujillo, Rocio', 'Pyles, Richard B.', 'Miller, Aaron L.', 'Alvarez-Fernandez, Pedro', 'Pong, Dan L.', 'Chonmaitree, Tasnee']",,,,
,PMC,Antibody-driven design of a human cytomegalovirus gHgLpUL128L subunit vaccine that selectively elicits potent neutralizing antibodies,http://dx.doi.org/10.1073/pnas.1415310111,PMC4273412,,,"The use of neutralizing antibodies to identify the most effective antigen has been proposed as a strategy to design vaccines capable of eliciting protective B-cell immunity. In this study, we analyzed the human antibody response to cytomegalovirus (human cytomegalovirus, HCMV) infection and found that antibodies to glycoprotein (g)B, a surface glycoprotein that has been developed as a HCMV vaccine, were primarily nonneutralizing. In contrast, most of the antibodies to the complex formed by gH, gL, protein (p)UL128, pUL130, and pUL131 (the gHgLpUL128L pentamer) neutralized HCMV infection with high potency. Based on this analysis, we developed a single polycistronic vector encoding the five pentamer genes separated by “self-cleaving” 2A peptides to generate a stably transfected CHO cell line constitutively secreting high levels of recombinant pentamer that displayed the functional antigenic sites targeted by human neutralizing antibodies. Immunization of mice with the pentamer formulated with different adjuvants elicited HCMV neutralizing antibody titers that persisted to high levels over time and that were a hundred- to thousand-fold higher than those found in individuals that recovered from primary HCMV infection. Sera from mice immunized with the pentamer vaccine neutralized infection of both epithelial cells and fibroblasts and prevented cell-to-cell spread and viral dissemination from endothelial cells to leukocytes. Neutralizing monoclonal antibodies from immunized mice showed the same potency as human antibodies and targeted the same as well as additional sites on the pentamer. These results illustrate with a relevant example a general and practical approach of analytic vaccinology for the development of subunit vaccines against complex pathogens.",,"['Kabanova, Anna', 'Perez, Laurent', 'Lilleri, Daniele', 'Marcandalli, Jessica', 'Agatic, Gloria', 'Becattini, Simone', 'Preite, Silvia', 'Fuschillo, Dario', 'Percivalle, Elena', 'Sallusto, Federica', 'Gerna, Giuseppe', 'Corti, Davide', 'Lanzavecchia, Antonio']",,,,
,PMC,Characterization of Cellular and Humoral Immune Responses After IBV Infection in Chicken Lines Differing in MBL Serum Concentration,http://dx.doi.org/10.1089/vim.2014.0088,PMC4259184,,,"Chickens from two inbred lines selected for high (L10H) or low (L10L) mannose-binding lectin (MBL) serum concentrations were infected with infectious bronchitis virus (IBV), and innate as well as adaptive immunological parameters were measured throughout the experimental period. Chickens with high MBL serum concentrations were found to have less viral load in the trachea than chickens with low MBL serum concentrations indicating that these chickens were less severely affected by the infection. This study is the first to show that MBL expression is present in the lungs of healthy chickens and that the expression is upregulated at days 3 postinfection (p.i.) in L10H chickens. Furthermore, in the liver of infected chickens, the MBL expression was upregulated at day 7 p.i., despite the fact that the MBL serum concentrations were decreased below baseline at that time point. The number of TCRγδ+CD8α+ cells in the blood of noninfected chickens increased from week 0 to 3 p.i. However, the number of cells was higher in L10H chickens than in L10L chickens throughout the experiment. No increase was observed in the number of TCRγδ+CD8α+ cells in the blood of the infected L10H and L10L chickens. The numbers of B cells at week 3 p.i. were higher for noninfected L10L chickens than for the other chickens. No differences were observed between the infected and noninfected L10H chickens or between the infected L10H and L10L chickens. Furthermore, at week 3 p.i., the number of monocytes was higher in infected and noninfected L10H chickens than in the infected and noninfected L10L chickens. Thus, these results indicate that MBL is produced locally and may be involved in the regulation of the cellular immune response after an IBV infection. However, MBL did not appear to influence the humoral immune response after IBV infection in this study.",,"['Kjærup, Rikke Munkholm', 'Dalgaard, Tina S.', 'Norup, Liselotte R.', 'Hamzic, Edin', 'Sørensen, Poul', 'Juul-Madsen, Helle R.']",,,,
,PMC,The Amino Acids 736–761 of the MERS-CoV Spike Protein Induce Neutralizing Antibodies: Implications for the Development of Vaccines and Antiviral Agents,http://dx.doi.org/10.1089/vim.2014.0080,PMC4259179,,,"Based on a bioinformatics analysis of the Middle East respiratory syndrome coronavvirus (MERS-CoV) S protein, we synthesized a panel of peptides coupled to keyhole limpet haemocyanin and used them to raise antibodies in rabbits. In addition, the recombinant receptor-binding domain (RBD) was used to raise polyclonal antibodies in mice. All of the antibodies raised by S-peptide immunisation were specific and sensitive for S protein expressed in transfected cells in the indirect immunofluorescence assay or Western blotting. The RBD efficiently elicited neutralizing antibodies against MERS-CoV by blocking viral entry at the binding step. Furthermore, we found that the SP3 peptide, corresponding to amino-acid residues 736–761 of the S protein, elicited robust neutralizing activities by blocking viral entry at the postbinding and membrane fusion steps. We conclude that amino-acid residues 736–761 of the S protein carry neutralizing epitopes that may be used in the development of vaccines and antiviral agents against MERS-CoV.",,"['Yang, Yang', 'Deng, Yao', 'Wen, Bo', 'Wang, Huijuan', 'Meng, Xin', 'Lan, Jiaming', 'Gao, George F.', 'Tan, Wenjie']",,,,
,PMC,Journal Watch,http://dx.doi.org/10.1177/1757177414553337,PMC5074108,,,,,"Wigglesworth, Neil",,,,
,PMC,"Emergence of travel: Associated dengue fever in a non-endemic, hilly state",http://dx.doi.org/10.4103/2277-9175.145744,PMC4260275,25538925,CC BY-NC-SA,"BACKGROUND: We assessed the occurrence of dengue fever in association with travel in a non-endemic hilly region. The clinical presentation and laboratory parameters of febrile patients with a travel history to an endemic region were studied, and the role of the laboratory in the diagnosis was affirmed. MATERIALS AND METHODS: Febrile patients presenting with clinical features defining dengue with a history of travel to an endemic area constituted the study group. Serum samples were tested for dengue-specific NS1 antigen and IgM, IgG antibodies. The demographic data were retrieved from the hospital information system. A hematological and biochemical workup was done and the results analyzed using percentage, proportion, mean, and median. RESULTS: Out of 189 febrile patients, 58 were reactive to serological tests for dengue, with 47 (81%) males. The presenting features were chills and rigors, myalgia, cough, sweating, and vomiting. Thrombocytopenia (74.35%), lymphopenia (52.94%), and leucopenia (47.05%) were present in early disease, with AST >34 IU/L in 58.97% of the patients. The NS1 antigen was detectable between three and seven days of fever and the IgM antibodies after five days. The positivities to only NS1, both NS1 and IgM, and IgM alone were 60.34, 27.58, and 10.34%, respectively, and the median duration of fever was five, seven, and ten days, respectively. One case of dengue hemorrhagic fever and one of probable secondary dengue infection with detectable IgG were encountered. CONCLUSION: Dengue fever remains unsuspected in febrile cases in non-endemic regions. History of travel is an essential criterion to suspect dengue. A non-specific clinical presentation eludes diagnosis. Serological tests for antigen and antibodies, and hematological and biochemical markers are vital for distinguishing the diagnosis.",2014 Nov 29,"['Verma, Santwana', 'Kanga, Anil', 'Singh, Digvijay', 'Verma, Ghanshyam K', 'Mokta, Kiran', 'Ganju, Sunite A', 'Sharma, Vineeta']",Adv Biomed Res,,,
,PMC,Development of human neutralizing monoclonal antibodies for prevention and therapy of MERS-CoV infections,http://dx.doi.org/10.1016/j.micinf.2014.11.008,PMC4308519,,,"The recent Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak poses a serious threat to public health. Here, we summarize recent advances in identifying human neutralizing monoclonal antibodies (mAbs) against MERS-CoV, describe their mechanisms of action, and analyze their potential for treatment of MERS-CoV infections.",,"['Ying, Tianlei', 'Li, Haoyang', 'Lu, Lu', 'Dimitrov, Dimiter S', 'Jiang, Shibo']",,,,
,PMC,Simian hemorrhagic fever virus: Recent advances,http://dx.doi.org/10.1016/j.virusres.2014.11.024,PMC4449332,,,"Simian hemorrhagic fever virus (SHFV) is an understudied arterivirus that typically causes asymptomatic, persistent infections in multiple species of African nonhuman primates (NHPs) which are natural hosts but fatal hemorrhagic fever disease in macaques. SHFV genomes found in different species of African primates have recently been sequenced but no biological data for these viruses has yet been reported. The sequence of one SHFV isolate from a long term persistently infected baboon showed a high degree of identity to the genome of SHFV-LVR, the prototype strain isolated in the 1960s. Similar to what was observed in early studies with the prototype SHFV isolate LVR, infection of Japanese macaques with 100 PFU of the baboon isolate efficiently induced fatal hemorrhagic fever disease in macaques. Consistent with the differential infection outcomes observed in macaques and baboons, SHFV infection of macaque macrophages and dendritic cells is more efficiently than that of baboons and infection induces pro39 inflammatory cytokine production in macaque but not baboon cells. A stable full-length SHFV LVR infectious clone was constructed and basic knowledge about the unique functions of SHFV has been expanded by several recent studies. The SHFV genome encodes extra genes compared to those of other arteriviruses; three instead of two papain-like protease one (PLP1) domains are encoded at the 5’ end and two adjacent sets of four minor structural proteins at the 3’ end. SHFV PLP1α, PLP1β and PLP1γ were each shown to be active proteases in vitro and the three expected nsp1proteins were detected in infected cells. The catalytic Cys of PLP1α is adjacent to an Ala instead of canonical Typ and PLP1γ is unique among arterivirus PLPs in being able to cleave at both downstream and upstream sites. Although the duplicated sets of SHFV minor structural proteins were predicted to be functionally redundant, data obtained with a set of mutant infectious clones, each with the start codon of one of the minor structural proteins mutated, showed that all eight of the minor structural proteins are required for production of infectious extracellular virus.",,"['Brinton, Margo A.', 'Di, Han', 'Vatter, Heather A.']",,,,
,PMC,Infectious causes of necrotizing enterocolitis,http://dx.doi.org/10.1016/j.clp.2014.10.012,PMC4328138,,,"Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency among premature infants. Although a large body of research has focused on understanding its pathogenesis, the exact mechanism has not been elucidated. Of particular interest is the potential causative role of infectious culprits in the development of NEC. A variety of reports describe bacterial, viral, and fungal infections occurring in association with NEC; however, no organism has emerged as being definitively involved in NEC pathogenesis. In this review, we summarize the body of research on infectious causes of necrotizing enterocolitis.",,"['Coggins, Sarah A.', 'Wynn, James L.', 'Weitkamp, Jörn-Hendrik']",,,,
,PMC,Providing nursing care to Ebola patients on the national stage: The National Institutes of Health experience,http://dx.doi.org/10.1016/j.outlook.2014.11.015,PMC4402233,,,,,"['Matlock, Ann Marie', 'Gutierrez, Debbie', 'Wallen, Gwenyth', 'Hastings, Clare']",,,,
,PMC,Receptor Recognition Mechanisms of Coronaviruses: a Decade of Structural Studies,http://dx.doi.org/10.1128/JVI.02615-14,PMC4338876,,,"Receptor recognition by viruses is the first and essential step of viral infections of host cells. It is an important determinant of viral host range and cross-species infection and a primary target for antiviral intervention. Coronaviruses recognize a variety of host receptors, infect many hosts, and are health threats to humans and animals. The receptor-binding S1 subunit of coronavirus spike proteins contains two distinctive domains, the N-terminal domain (S1-NTD) and the C-terminal domain (S1-CTD), both of which can function as receptor-binding domains (RBDs). S1-NTDs and S1-CTDs from three major coronavirus genera recognize at least four protein receptors and three sugar receptors and demonstrate a complex receptor recognition pattern. For example, highly similar coronavirus S1-CTDs within the same genus can recognize different receptors, whereas very different coronavirus S1-CTDs from different genera can recognize the same receptor. Moreover, coronavirus S1-NTDs can recognize either protein or sugar receptors. Structural studies in the past decade have elucidated many of the puzzles associated with coronavirus-receptor interactions. This article reviews the latest knowledge on the receptor recognition mechanisms of coronaviruses and discusses how coronaviruses have evolved their complex receptor recognition pattern. It also summarizes important principles that govern receptor recognition by viruses in general.",,"Li, Fang",,,,
,PMC,Interferon-Induced Ifit Proteins: Their Role in Viral Pathogenesis,http://dx.doi.org/10.1128/JVI.02744-14,PMC4325746,,,"A major component of the protective antiviral host defense is contributed by the intracellular actions of the proteins encoded by interferon-stimulated genes (ISGs); among these are the interferon-induced proteins with tetratricopeptide repeats (IFITs), consisting of four members in human and three in mouse. IFIT proteins do not have any known enzyme activity. Instead, they inhibit virus replication by binding and regulating the functions of cellular and viral proteins and RNAs. Although all IFITs are comprised of multiple copies of the degenerate tetratricopeptide repeats, their distinct tertiary structures enable them to bind different partners and affect host-virus interactions differently. The recent use of Ifit knockout mouse models has revealed novel antiviral functions of these proteins and new insights into the specificities of ISG actions. This article focuses on human and murine IFIT1 and IFIT2 by reviewing their mechanisms of action, their critical roles in protecting mice from viral pathogenesis, and viral strategies to evade IFIT action.",,"['Fensterl, Volker', 'Sen, Ganes C.']",,,,
,PMC,Unraveling the Web of Viroinformatics: Computational Tools and Databases in Virus Research,http://dx.doi.org/10.1128/JVI.02027-14,PMC4300767,,,"The beginning of the second century of research in the field of virology (the first virus was discovered in 1898) was marked by its amalgamation with bioinformatics, resulting in the birth of a new domain—viroinformatics. The availability of more than 100 Web servers and databases embracing all or specific viruses (for example, dengue virus, influenza virus, hepatitis virus, human immunodeficiency virus [HIV], hemorrhagic fever virus [HFV], human papillomavirus [HPV], West Nile virus, etc.) as well as distinct applications (comparative/diversity analysis, viral recombination, small interfering RNA [siRNA]/short hairpin RNA [shRNA]/microRNA [miRNA] studies, RNA folding, protein-protein interaction, structural analysis, and phylotyping and genotyping) will definitely aid the development of effective drugs and vaccines. However, information about their access and utility is not available at any single source or on any single platform. Therefore, a compendium of various computational tools and resources dedicated specifically to virology is presented in this article.",,"['Sharma, Deepak', 'Priyadarshini, Pragya', 'Vrati, Sudhanshu']",,,,
,PMC,The nsp3 Macrodomain Promotes Virulence in Mice with Coronavirus-Induced Encephalitis,http://dx.doi.org/10.1128/JVI.02596-14,PMC4300739,,,"All coronaviruses encode a macrodomain containing ADP-ribose-1″-phosphatase (ADRP) activity within the N terminus of nonstructural protein 3 (nsp3). Previous work showed that mouse hepatitis virus strain A59 (MHV-A59) with a mutated catalytic site (N1348A) replicated similarly to wild-type virus but was unable to cause acute hepatitis in mice. To determine whether this attenuated phenotype is applicable to multiple disease models, we mutated the catalytic residue in the JHM strain of MHV (JHMV), which causes acute and chronic encephalomyelitis, using a newly developed bacterial artificial chromosome (BAC)-based MHV reverse genetics system. Infection of mice with the macrodomain catalytic point mutant virus (N1347A) resulted in reductions in lethality, weight loss, viral titers, proinflammatory cytokine and chemokine expression, and immune cell infiltration in the brain compared to mice infected with wild-type virus. Specifically, macrophages were most affected, with approximately 2.5-fold fewer macrophages at day 5 postinfection in N1347A-infected brains. Tumor necrosis factor (TNF) and interferon (IFN) signaling were not required for effective host control of mutant virus as all N1347A virus-infected mice survived the infection. However, the adaptive immune system was required for protection since N1347A virus was able to cause lethal encephalitis in RAG1(−/−) (recombination activation gene 1 knockout) mice although disease onset was modestly delayed. Overall, these results indicate that the BAC-based MHV reverse genetics system will be useful for studies of JHMV and expand upon previous studies, showing that the macrodomain is critical for the ability of coronaviruses to evade the immune system and promote viral pathogenesis. IMPORTANCE Coronaviruses are an important cause of human and veterinary diseases worldwide. Viral processes that are conserved across a family are likely to be good targets for the development of antiviral therapeutics and vaccines. The macrodomain is a ubiquitous structural domain and is also conserved among all coronaviruses. The coronavirus macrodomain has ADP-ribose-1″-phosphatase activity; however, its function during infection remains unclear as does the reason that coronaviruses have maintained this enzymatic activity throughout evolution. For MHV, this domain has now been shown to promote multiple types of disease, including hepatitis and encephalitis. These data indicate that this domain is vital for the virus to replicate and cause disease. Understanding the mechanism used by this enzyme to promote viral pathogenesis will open up novel avenues for therapies and may give further insight into the role of macrodomain proteins in the host cell since these proteins are found in all living organisms.",,"['Fehr, Anthony R.', 'Athmer, Jeremiah', 'Channappanavar, Rudragouda', 'Phillips, Judith M.', 'Meyerholz, David K.', 'Perlman, Stanley']",,,,
,PMC,Coronavirus nonstructural protein 1: common and distinct functions in the regulation of host and viral gene expression,http://dx.doi.org/10.1016/j.virusres.2014.11.019,PMC4444399,,,"The recent emergence of two highly pathogenic human coronaviruses (CoVs), severe acute respiratory syndrome CoV and Middle East respiratory syndrome CoV, has ignited a strong interest in the identification of viral factors that determine the virulence and pathogenesis of CoVs. The nonstructural protein 1 (nsp1) of CoVs has attracted considerable attention in this regard as a potential virulence factor and a target for CoV vaccine development because of accumulating evidence that point to its role in the downregulation of host innate immune responses to CoV infection. Studies have revealed both functional conservation and mechanistic divergence among the nsp1 of different mammalian CoVs in perturbing host gene expression and antiviral responses. This review summarizes the current knowledge about the biological functions of CoV nsp1 that provides an insight into the novel strategies utilized by this viral protein to modulate host and viral gene expression during CoV infection.",,"['Narayanan, Krishna', 'Ramirez, Sydney I.', 'Lokugamage, Kumari G.', 'Makino, Shinji']",,,,
,PMC,4EBP1/eIF4E and p70S6K/RPS6 Axes Play Critical and Distinct Roles in Hepatocarcinogenesis Driven by AKT and N-Ras Protooncogenes,http://dx.doi.org/10.1002/hep.27396,PMC4280310,,,"Concomitant expression of activated forms of AKT and Ras in the mouse liver (AKT/Ras) leads to rapid tumor development via strong activation of the mTORC1 pathway. mTORC1 functions via regulating p70S6K/RPS6 and 4EBP1/eIF4E cascades. How these cascades contribute to hepatocarcinogenesis remains unknown. Here, we show that inhibition of RPS6 pathway via Rapamycin effectively suppressed, whereas blockade of the 4EBP1/eIF4E cascade by 4EBP1A4, an unphosphorylatable form of 4EBP1, significantly delayed, AKT/Ras induced hepatocarcinogenesis. Combined treatment with Rapamycin and 4EBP1A4 completely inhibited AKT/Ras hepatocarcinogenesis. This strong anti-neoplastic effect was successfully recapitulated by ablating Raptor, the major subunit of mTORC1, in AKT/Ras-overexpressing livers. Furthermore, we demonstrate that overexpression of eIF4E, the protooncogene whose activity is specifically inhibited by 4EBP1, resulted in HCC development in cooperation with activated Ras. Mechanistically, we identified the ENTPD5/AK1/CMPK1 axis and the mitochondrial biogenesis pathway as targets of the 4EBP1/eIF4E cascade in AKT/Ras and Ras/eIF4E livers as well as in human HCC cell lines and tissues. CONCLUSIONS: Complete inhibition of mTORC1 is required to suppress liver cancer development induced by AKT and Ras protooncogenes in mice. The mTORC1 effectors, RPS6 and eIF4E, play distinct roles and are both necessary for AKT/Ras hepatocarcinogenesis. These new findings might open the way for innovative therapies against human hepatocellular carcinoma.",,"['Wang, Chunmei', 'Cigliano, Antonio', 'Jiang, Lijie', 'Li, Xiaolei', 'Fan, Biao', 'Pilo, Maria G.', 'Liu, Yan', 'Gui, Bing', 'Sini, Marcella', 'Smith, Jeffrey W.', 'Dombrowski, Frank', 'Calvisi, Diego F.', 'Evert, Matthias', 'Chen, Xin']",,,,
,PMC,Chemical-free inactivated whole influenza virus vaccine prepared by ultrashort pulsed laser treatment,http://dx.doi.org/10.1117/1.JBO.20.5.051008,PMC4242973,,,"There is an urgent need for rapid methods to develop vaccines in response to emerging viral pathogens. Whole inactivated virus (WIV) vaccines represent an ideal strategy for this purpose; however, a universal method for producing safe and immunogenic inactivated vaccines is lacking. Conventional pathogen inactivation methods such as formalin, heat, ultraviolet light, and gamma rays cause structural alterations in vaccines that lead to reduced neutralizing antibody specificity, and in some cases, disastrous T helper type 2-mediated immune pathology. We have evaluated the potential of a visible ultrashort pulsed (USP) laser method to generate safe and immunogenic WIV vaccines without adjuvants. Specifically, we demonstrate that vaccination of mice with laser-inactivated H1N1 influenza virus at about a 10-fold lower dose than that required using conventional formalin-inactivated influenza vaccines results in protection against lethal H1N1 challenge in mice. The virus, inactivated by the USP laser irradiation, has been shown to retain its surface protein structure through hemagglutination assay. Unlike conventional inactivation methods, laser treatment did not generate carbonyl groups in protein, thereby reducing the risk of adverse vaccine-elicited T helper type 2 responses. Therefore, USP laser treatment is an attractive potential strategy to generate WIV vaccines with greater potency and safety than vaccines produced by current inactivation techniques.",,"['Tsen, Shaw-Wei David', 'Donthi, Nisha', 'La, Victor', 'Hsieh, Wen-Han', 'Li, Yen-Der', 'Knoff, Jayne', 'Chen, Alexander', 'Wu, Tzyy-Choou', 'Hung, Chien-Fu', 'Achilefu, Samuel', 'Tsen, Kong-Thon']",,,,
,PMC,Respiratory Syncytial Virus Genomic Load and Disease Severity Among Children Hospitalized With Bronchiolitis: Multicenter Cohort Studies in the United States and Finland,http://dx.doi.org/10.1093/infdis/jiu658,PMC4481613,,,"Background. We investigated whether children with a higher respiratory syncytial virus (RSV) genomic load are at a higher risk of more-severe bronchiolitis. Methods. Two multicenter prospective cohort studies in the United States and Finland used the same protocol to enroll children aged <2 years hospitalized for bronchiolitis and collect nasopharyngeal aspirates. By using real-time polymerase chain reaction analysis, patients were classified into 3 genomic load status groups: low, intermediate, and high. Outcome measures were a length of hospital stay (LOS) of ≥3 days and intensive care use, defined as admission to the intensive care unit or use of mechanical ventilation. Results. Of 2615 enrolled children, 1764 (67%) had RSV bronchiolitis. Children with a low genomic load had a higher unadjusted risk of having a length of stay of ≥3 days (52%), compared with children with intermediate and those with high genomic loads (42% and 51%, respectively). In a multivariable model, the risk of having a length of stay of ≥3 days remained significantly higher in the groups with intermediate (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.20–1.69) and high (OR, 1.58; 95% CI, 1.29–1.94) genomic loads. Similarly, children with a high genomic load had a higher risk of intensive care use (20%, compared with 15% and 16% in the groups with low and intermediate genomic loads, respectively). In a multivariable model, the risk remained significantly higher in the group with a high genomic load (OR, 1.43; 95% CI, 1.03–1.99). Conclusion. Children with a higher RSV genomic load had a higher risk for more-severe bronchiolitis.",,"['Hasegawa, Kohei', 'Jartti, Tuomas', 'Mansbach, Jonathan M.', 'Laham, Federico R.', 'Jewell, Alan M.', 'Espinola, Janice A.', 'Piedra, Pedro A.', 'Camargo, Carlos A.']",,,,
,PMC,Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10,http://dx.doi.org/10.1002/eji.201444823,PMC4293323,,,"Forkhead box P3 (Foxp3)(+) regulatory T (Treg) cells maintain the immune tolerance and prevent inflammatory responses in the periphery. However, the presence of Treg cells in the central nervous system under steady state has not been studied. Here, for the first time, we show a substantial TCR(αβ)(+)CD4(+)Foxp3(+) T-cell population (cerebral Treg cells) in the normal rat cerebrum, constituting more than 15% of the cerebral CD4(+) T-cell compartment. Cerebral Treg cells showed an activated/memory phenotype and expressed many Treg-cell signature genes at higher levels than peripheral Treg cells. Consistent with their activated/memory phenotype, cerebral Treg cells robustly restrained the LPS-induced inflammatory responses of brain microglia/macrophages, suggesting a role in maintaining the cerebral homeostasis by inhibiting the neuroinflammation. In addition, brain astrocytes were the helper cells that sustained Foxp3 expression in Treg cells through IL-2/STAT5 signaling, showing that the interaction between astrocytes and Treg cells contributes to the maintenance of Treg-cell identity in the brain. Taken together, our work represents the first study to characterize the phenotypic and functional features of Treg cells in the normal rat cerebrum. Our data have provided a novel insight for the contribution of Treg cells to the immunosurveillance and immunomodulation in the cerebrum under steady state.",,"['Xie, Luokun', 'Choudhury, Gourav Roy', 'Winters, Ali', 'Yang, Shao-Hua', 'Jin, Kunlin']",,,,
,PMC,Myeloid cell TRAF3 regulates immune responses and inhibits inflammation and tumor development in mice(),http://dx.doi.org/10.4049/jimmunol.1401548,PMC4272913,,,"Myeloid cells, including granulocytes, monocytes, macrophages and dendritic cells, are crucial players in innate immunity and inflammation. These cells constitutively or inducibly express a number of receptors of the TNF receptor and Toll-like receptor (TLR) families, whose signals are transduced by TRAF molecules. In vitro studies showed that TRAF3 is required for TLR-induced type I interferon production, but the in vivo function of TRAF3 in myeloid cells remains unknown. Here we report the generation and characterization of myeloid cell-specific TRAF3-deficient (M-TRAF3(−/−)) mice, which allowed us to gain insights into the in vivo functions of TRAF3 in myeloid cells. We found that TRAF3 ablation did not affect the maturation or homeostasis of myeloid cells in young adult mice, even though TRAF3-deficient macrophages and neutrophils exhibited constitutive NF-κB2 activation. However, in response to injections with LPS (a bacterial mimic) or polyI:C (a viral mimic), M-TRAF3(−/−) mice exhibited an altered profile of cytokine production. M-TRAF3(−/−) mice immunized with T cell-independent (TI) and -dependent (TD) antigens displayed elevated TI IgG3 as well as TD IgG2b responses. Interestingly, 15–22 month old M-TRAF3(−/−) mice spontaneously developed chronic inflammation or tumors, often affecting multiple organs. Taken together, our findings indicate that TRAF3 expressed in myeloid cells regulates immune responses in myeloid cells and acts to inhibit inflammation and tumor development in mice.",,"['Lalani, Almin I.', 'Moore, Carissa R.', 'Luo, Chang', 'Kreider, Benjamin Z.', 'Liu, Yan', 'Morse, Herbert C.', 'Xie, Ping']",,,,
,PMC,"Estimating Potential Incidence of MERS-CoV Associated with Hajj Pilgrims to Saudi Arabia, 2014",http://dx.doi.org/10.1371/currents.outbreaks.c5c9c9abd636164a9b6fd4dbda974369,PMC4323406,25685624,CC BY,"Between March and June 2014 the Kingdom of Saudi Arabia (KSA) had a large outbreak of MERS-CoV, renewing fears of a major outbreak during the Hajj this October. Using KSA Ministry of Health data, the MERS-CoV Scenario and Modeling Working Group forecast incidence under three scenarios. In the expected incidence scenario, we estimate 6.2 (95% Prediction Interval [PI]: 1–17) pilgrims will develop MERS-CoV symptoms during the Hajj, and 4.0 (95% PI: 0–12) foreign pilgrims will be infected but return home before developing symptoms. In the most pessimistic scenario, 47.6 (95% PI: 32–66) cases will develop symptoms during the Hajj, and 29.0 (95% PI: 17–43) will be infected but return home asymptomatic. Large numbers of MERS-CoV cases are unlikely to occur during the 2014 Hajj even under pessimistic assumptions, but careful monitoring is still needed to detect possible mass infection events and minimize introductions into other countries.",2014 Nov 24,"['Lessler, Justin', 'Rodriguez-Barraquer, Isabel', 'Cummings, Derek A.T.', 'Garske, Tini', 'Van Kerkhove, Maria', 'Mills, Harriet', 'Truelove, Shaun', 'Hakeem, Rafat', 'Albarrak, Ali', 'Ferguson, Neil M.', None]",PLoS Curr,,,
,PMC,"Detecting the emergence of novel, zoonotic viruses pathogenic to humans",http://dx.doi.org/10.1007/s00018-014-1785-y,PMC4629502,,,"RNA viruses, with their high potential for mutation and epidemic spread, are the most common class of pathogens found as new causes of human illness. Despite great advances made in diagnostic technology since the 1950s, the annual rate at which novel virulent viruses have been found has remained at 2–3. Most emerging viruses are zoonoses; they have jumped from mammal or bird hosts to humans. An analysis of virus discovery indicates that the small number of novel viruses discovered annually is an artifact of inadequate surveillance in tropical and subtropical countries, where even established endemic pathogens are often misdiagnosed. Many of the emerging viruses of the future are already infecting humans but remain to be uncovered by a strategy of disease surveillance in selected populations.",,"Rosenberg, Ronald",,,,
,PMC,Host cell proteases: critical determinants of coronavirus tropism and pathogenesis,http://dx.doi.org/10.1016/j.virusres.2014.11.021,PMC4465284,,,"Coronaviruses are a large group of enveloped, single-stranded positive-sense RNA viruses that infect a wide range of avian and mammalian species, including humans. The emergence of deadly human coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV) have bolstered research in these viral and often zoonotic pathogens. While coronavirus cell and tissue tropism, host range, and pathogenesis are initially controlled by interactions between the spike envelope glycoprotein and host cell receptor, it is becoming increasingly apparent that proteolytic activation of spike by host cell proteases also plays a critical role. Coronavirus spike proteins are the main determinant of entry as they possess both receptor binding and fusion functions. Whereas binding to the host cell receptor is an essential first step in establishing infection, the proteolytic activation step is often critical for the fusion function of spike, as it allows for controlled release of the fusion peptide into target cellular membranes. Coronaviruses have evolved multiple strategies for proteolytic activation of spike, and a large number of host proteases have been shown to proteolytically process the spike protein. These include, but are not limited to, endosomal cathepsins, cell surface transmembrane protease/serine (TMPRSS) proteases, furin, and trypsin. This review focuses on the diversity of strategies coronaviruses have evolved to proteolytically activate their fusion protein during spike protein biosynthesis and the critical entry step of their life cycle, and highlights important findings on how proteolytic activation of coronavirus spike influences tissue and cell tropism, host range and pathogenicity.",,"['Millet, Jean Kaoru', 'Whittaker, Gary R.']",,,,
,PMC,SHAPE Analysis of the RNA Secondary Structure of the Mouse Hepatitis Virus 5′ Untranslated Region and N-Terminal Nsp1 Coding Sequences,http://dx.doi.org/10.1016/j.virol.2014.11.001,PMC4280293,,,"SHAPE technology was used to analyze RNA secondary structure of the 5′ most 474 nts of the MHV-A59 genome encompassing the minimal 5′ cis-acting region required for defective interfering RNA replication. The structures generated were in agreement with previous characterizations of SL1 through SL4 and two recently predicted secondary structure elements, S5 and SL5A. SHAPE provided biochemical support for four additional stem-loops not previously functionally investigated in MHV. Secondary structure predictions for 5′ regions of MHV-A59, BCoV and SARS-CoV were similar despite high sequence divergence. The pattern of SHAPE reactivity of in virio genomic RNA, ex virio genomic RNA, and in vitro synthesized RNA were similar, suggesting that binding of N protein or other proteins to virion RNA fails to protect the RNA from reaction with lipid permeable SHAPE reagent. Reverse genetic experiments suggested that SL5C and SL6 within the nsp1 coding sequence are not required for viral replication.",,"['Yang, Dong', 'Liu, Pinghua', 'Wudeck, Elyse V.', 'Giedroc, David P.', 'Leibowitz, Julian L.']",,,,
,PMC,Burden of influenza infection in hospitalised children below 6 months of age and above in Hong Kong from 2005 to 2011(),http://dx.doi.org/10.1016/j.vaccine.2014.04.063,PMC5355210,24837762,CC BY-NC-SA,"The World Health Organization recommends vaccination of pregnant women for seasonal influenza that can also protect infants aged below 6 months. We estimated incidence and disease burden of influenza in hospitalised children below and above 6 months of age in Hong Kong during a 6 year period. Discharge diagnoses for all admissions to public Hong Kong Hospital Authority hospitals, recorded in a central computerised database (Clinical Management System, CMS), were analysed for the period April 2005 to March 2011. Incidence estimates of influenza disease by age group were derived from CMS ICD codes 487–487.99. Laboratory-confirmed influenza infections from a single surveillance hospital were then linked to the CMS entries to assess possible over- and under-diagnosis of influenza based on CMS codes alone. Influenza was recorded as any primary or any secondary diagnosis in 1.3% (1158/86,582) of infants aged above 6 days to below 6 months and 4.3% (20,230/471,482) of children above 6 days to below 18 years. The unadjusted incidence rates per 100,000 person-years based on any CMS diagnosis of influenza in all admission to Hong Kong public hospitals were 627 in the below 2 months of age group and 1762 in the 2 month to below 6 month group. Incidence of hospitalisation for influenza in children was highest from 2 months to below 6 months. In the absence of vaccines for children below 6 months of age, effective vaccination of pregnant women may have a significant impact on reducing influenza hospitalisations in this age group.",2014 Nov 20,"['Nelson, E. Anthony S.', 'Ip, Margaret', 'Tam, John S.', 'Mounts, Anthony W.', 'Chau, Sze Lok', 'Law, Shu Kei', 'Goggins, William', 'Simpson, Lucy A.', 'Chan, Paul K.S.']",Vaccine,,,
,PMC,Receptor-binding domain-based subunit vaccines against MERS-CoV,http://dx.doi.org/10.1016/j.virusres.2014.11.013,PMC4439384,,,"Development of effective vaccines, in particular, subunit-based vaccines, against emerging Middle East respiratory syndrome (MERS) caused by the MERS coronavirus (MERS-CoV) will provide the safest means of preventing the continuous spread of MERS in humans and camels. This review briefly describes the structure of the MERS-CoV spike (S) protein and its receptor-binding domain (RBD), discusses the current status of MERS vaccine development, and illustrates the strategies used to develop RBD-based subunit vaccines against MERS. It also summarizes currently available animal models for MERS-CoV and proposes a future direction for MERS vaccines. Taken together, this review will assist researchers working to develop effective and safe subunit vaccines against MERS-CoV and any other emerging coronaviruses that might cause future pandemics.",,"['Zhang, Naru', 'Tang, Jian', 'Lu, Lu', 'Jiang, Shibo', 'Du, Lanying']",,,,
,PMC,Fruits of Virus Discovery: New Pathogens and New Experimental Models,http://dx.doi.org/10.1128/JVI.01194-14,PMC4300757,,,"The advent of high-throughput sequencing has led to a tremendous increase in the rate of discovery of viral sequences. In some instances, novel pathogens have been identified. What has been less well appreciated is that novel virus discoveries in distinct hosts have led to the establishment of unique experimental systems to define host-virus interactions. These new systems have opened new frontiers in the study of fundamental virology and infectious disease.",,"Wang, David",,,,
,PMC,A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques,http://dx.doi.org/10.1016/j.virol.2014.10.018,PMC4304765,,,"Simian hemorrhagic fever virus is an arterivirus that naturally infects species of African nonhuman primates causing acute or persistent asymptomatic infections. Although it was previously estimated that 1% of baboons are SHFV-positive, more than 10% of wild-caught and captive-bred baboons tested were SHFV positive and the infections persisted for more than 10 years with detectable virus in the blood (100–1000 genomes/ml). The sequences of two baboon SHFV isolates that were amplified by a single passage in primary macaque macrophages showed a very high degree of identity to each other as well as to the genome of SHFV-LVR, a laboratory strain isolated in the 1960s. Infection of Japanese macaques with 100 PFU of a baboon isolate consistently produced high level viremia, pro-inflammatory cytokines, elevated tissue factor levels and clinical signs indicating coagulation defects. The baboon virus isolate provides a reliable BSL2 model of viral hemorrhagic fever disease in macaques.",,"['Vatter, Heather A.', 'Donaldson, Eric F.', 'Huynh, Jeremy', 'Rawlings, Stephanie', 'Manoharan, Minsha', 'Legasse, Alfred', 'Planer, Shannon', 'Dickerson, Mary F.', 'Lewis, Anne D.', 'Colgin, Lois M.A.', 'Axthelm, Michael K.', 'Pecotte, Jerilyn K.', 'Baric, Ralph S.', 'Wong, Scott W.', 'Brinton, Margo A.']",,,,
,PMC,The Role of Immunophilins in Viral Infection,http://dx.doi.org/10.1016/j.bbagen.2014.11.011,PMC4491039,,,"BACKGROUND: Tremendous progress has been made in the past 20 years in understanding the roles played by immunophilins, and in particular the cyclophilins, in supporting the replication cycles of human viruses. A growing body of genetic and biochemical evidence and data from clinical trials confirms that cyclophilins are essential cofactors that contribute to establishing a permissive environment within the host cell that supports the replication of HIV-1 and HCV. Cyclophilin A regulates HIV-1 replication kinetics and infectivity, modulates sensitivity to host restriction factors, and cooperates in the transit of the pre-integration complex into the nucleus of infected cells. Cyclophilin A is an essential cofactor whose expression supports HCV-specific RNA replication in human hepatocytes. GENERAL SIGNIFICANCE: Peptidyl-prolyl isomerase inhibitors have been used in clinical trials to validate cyclophilins as antiviral targets for the treatment of HIV-1 and Chronic Hepatitis C virus infection and as molecular probes to identify the roles played by immunophilins in supporting the replication cycles of human viruses. SCOPE OF REVIEW: This review summarizes emerging research that defines the functions of immunophilins in supporting the replication cycles of HIV-1, HCV, HBV, coronaviruses, and other viral pathogens and describes new information that suggests a role for immunophilins in regulating innate immune responses against chronic viral infection. MAJOR CONCLUSIONS: The dependence on cyclophilins by evolutionarily distinct viruses for accomplishing various steps in replication such as viral entry, initiation of genomic nucleic acid replication, viral genome uncoating, nuclear import and nuclear entry, emphasizes the potential of cyclophilin inhibitors as therapeutic agents.",,"['Hopkins, Sam', 'Gallay, Philippe A.']",,,,
,PMC,Extracellular cyclophilins in health and disease,http://dx.doi.org/10.1016/j.bbagen.2014.11.013,PMC4436085,,,"BACKGROUND: Extracellular cyclophilins (eCyPs) are pro-inflammatory factors implicated in pathogenesis of a number of inflammatory diseases. Most pathogenic activities of eCyPs are related to their chemotactic activity towards leukocytes, which is mediated by eCyP receptor on target cells, CD147, and involves peptydil-prolyl cis-trans isomerase activity of cyclophilins. This activity is inhibited by cyclosporine A (CsA) and non-immunosuppressive derivatives of this drug. Accumulating evidence for the role of eCyPs in disease pathogenesis stimulated research on the mechanisms of eCyP-initiated events, resulting in identification of multiple signaling pathways, characterization of a variety of effector molecules released from eCyP-treated cells, and synthesis of CsA derivatives specifically blocking eCyPs. However, a number of important questions related to the mode of action of eCyPs remain unanswered. SCOPE OF REVIEW: In this article, we integrate available information on release and function of extracellular cyclophilins into a unified model, focusing on outstanding issues that need to be clarified. MAJOR CONCLUSIONS: Extracellular cyclophilins are critical players in pathogenesis of a number of inflammatory diseases. Their mechanism of action involves interaction with the receptor, CD147, and initiation of a poorly characterized signal transduction process culminating in chemotaxis and production of pro-inflammatory factors. GENERAL SIGNIFICANCE: Extracellular cyclophilins present an attractive target for therapeutic interventions that can be used to alleviate symptoms and consequences of acute and chronic inflammation.",,"Bukrinsky, Michael",,,,
,PMC,Formatted for Journal of Clinical Virology,http://dx.doi.org/10.1016/j.jcv.2014.11.006,PMC4403738,,,"BACKGROUND: Human rhinovirus (HRV) infections are highly prevalent, genetically diverse, and associated with both mild upper respiratory tract and more severe lower tract illnesses (LRTI). OBJECTIVE: To characterize the molecular epidemiology of HRV infections in young children seeking acute medical care. STUDY DESIGN: Nasal swabs collected from symptomatic children <3 years of age receiving care in the Emergency and Urgent Care Departments at Seattle Children's Hospital were analyzed by a rapid polymerase chain reaction (PCR) system (FilmArray®) for multiple viruses including HRV/enterovirus. HRV-positive results were confirmed by laboratory-developed real-time reverse transcription PCR (LD-PCR). Clinical data were collected by chart review. A subset of samples was selected for sequencing using the 5’ noncoding region. Associations between LRTI and HRV species and genotypes were estimated using logistic regression analysis. RESULTS: Of 595 samples with HRV/enterovirus detected by FilmArray, 474 (80%) were confirmed as HRV by LD-PCR. 211 (96%) of 218 selected samples were sequenced; HRV species A, B, and C were identified in 133 (63%), 6 (3%), and 72 (34%), respectively. LRTI was more common in HRVC than HRV-A illness episodes (adjusted OR [95% CI] 2.35[1.03-5.35). Specific HRV-A and HRV-C genotypes detected in multiple patients were associated with a greater proportion of LRTI episodes. In 18 patients with >1 HRV-positive illness episodes, a distinct genotype was detected in each. CONCLUSION: Diverse HRV genotypes circulated among symptomatic children during the study period. We found an association between HRV-C infections and LRTI in this patient population and evidence of association between specific HRV genotypes and LRTI.",,"['Martin, Emily K.', 'Kuypers, Jane', 'Chu, Helen Y.', 'Lacombe, Kirsten', 'Qin, Xuan', 'Strelitz, Bonnie', 'Bradford, Miranda', 'Jones, Charla', 'Klein, Eileen J.', 'Englund, Janet A.']",,,,
,PMC,"Expression, crystallization and preliminary crystallographic study of the functional mutant (N60K) of nonstructural protein 9 from Human coronavirus HKU1",http://dx.doi.org/10.1107/S2053230X14023085,PMC4259225,,,"Human coronavirus HKU1 (HCoV-HKU1), which mainly causes acute self-limited respiratory-tract infections, belongs to group A of the Betacoronavirus genus. Coronavirus genomes encode 16 nonstructural proteins (nsp1–16), which assemble into a large replication–transcription complex mediating virus propagation. Nonstructural protein 9, which binds to the single-stranded DNA/RNA, has been shown to be indispensible for viral replication. Interestingly, a functional mutant (N60K) of nsp9 was identified to compensate for a 6 nt insertion mutation of the 3′-untranslated region (UTR), which is critical for viral RNA synthesis. It has been proposed that the N60K mutation may cause certain conformational changes of nsp9 to rescue the defective insertion mutant. To further investigate the underlying structural mechanism, the N60K mutant of nsp9 from HCoV-HKU1 was successfully crystallized in this study. The crystals diffracted to 2.6 Å resolution and belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 31.9, b = 85.0, c = 95.0 Å. Two molecules were identified per asymmetric unit.",,"['Chen, Xia', 'Tan, Yusheng', 'Wang, Fenghua', 'Wang, Jinshan', 'Zhao, Qi', 'Li, Shuang', 'Fu, Sheng', 'Chen, Cheng', 'Yang, Haitao']",,,,
,PMC,Crystallization and preliminary crystallographic study of Feline infectious peritonitis virus main protease in complex with an inhibitor,http://dx.doi.org/10.1107/S2053230X14022390,PMC4259223,,,"Feline infectious peritonitis virus (FIPV) causes a lethal systemic granulomatous disease in wild and domestic cats around the world. Currently, no effective vaccines or drugs have been developed against it. As a member of the genus Alphacoronavirus, FIPV encodes two polyprotein precursors required for genome replication and transcription. Each polyprotein undergoes extensive proteolytic processing, resulting in functional subunits. This process is mainly mediated by its genome-encoded main protease, which is an attractive target for antiviral drug design. In this study, the main protease of FIPV in complex with a Michael acceptor-type inhibitor was crystallized. The complex crystals diffracted to 2.5 Å resolution and belonged to space group I422, with unit-cell parameters a = 112.3, b = 112.3, c = 102.1 Å. There is one molecule per asymmetric unit.",,"['Wang, Jinshan', 'Wang, Fenghua', 'Tan, Yusheng', 'Chen, Xia', 'Zhao, Qi', 'Fu, Sheng', 'Li, Shuang', 'Chen, Cheng', 'Yang, Haitao']",,,,
,PMC,Crystallization and preliminary crystallographic study of Porcine epidemic diarrhea virus main protease in complex with an inhibitor,http://dx.doi.org/10.1107/S2053230X14021876,PMC4259222,,,"Porcine epidemic diarrhea virus (PEDV) mainly infects neonatal pigs, resulting in significant morbidity and mortality. Owing to problems such as long periods of virus shedding, existing vaccines cannot provide complete protection from PEDV infection. The PEDV genome encodes two polyprotein precursors required for genome replication and transcription. Each polyprotein undergoes extensive proteolytic processing, resulting in functional subunits. This process is mainly mediated by its genome-encoded main protease, which is an attractive target for antiviral drug design. In this study, the main protease of Porcine epidemic diarrhea virus in complex with a Michael acceptor was crystallized. The complex crystals diffracted to 2.5 Å resolution and belonged to space group R3, with unit-cell parameters a = 175.3, b = 175.3, c = 58.7 Å. Two molecules were identified per asymmetric unit.",,"['Tan, Yusheng', 'Wang, Fenghua', 'Chen, Xia', 'Wang, Jinshan', 'Zhao, Qi', 'Li, Shuang', 'Wang, Zefang', 'Fu, Sheng', 'Chen, Cheng', 'Yang, Haitao']",,,,
,PMC,Does screening keep Ebola out of USA?,http://dx.doi.org/10.4172/2329-9088.1000177,PMC4325372,,,,,"['Schieffelin, John S', 'Xu, Tan', 'Sun, Wenjie']",,,,
,PMC,"Inhaled anti-infective chemotherapy for respiratory tract infections: Successes, challenges and the road ahead",http://dx.doi.org/10.1016/j.addr.2014.11.004,PMC4429008,,,"One of the most common causes of illnesses in humans is from respiratory tract infections caused by bacterial, viral or fungal pathogens. Inhaled anti-infective drugs are crucial for the prophylaxis and treatment of respiratory tract infections. The benefit of anti-infective drug delivery via inhalation is that it affords delivery of sufficient therapeutic dosages directly to the primary site of infection, while minimizing the risks of systemic toxicity or avoiding potential suboptimal pharmacokinetics/pharmacodynamics associated with systemic drug exposure. This review provides an up-to-date treatise of approved and novel developmental inhaled anti-infective agents, with particular attention to effective strategies for their use, pulmonary pharmacokinetic properties and safety.",,"['Velkov, Tony', 'Rahim, Nusaibah Abdul', 'Zhou, Qi (Tony)', 'Chan, Hak-Kim', 'Li, Jian']",,,,
,PMC,A Patient Self-collection Method for Longitudinal Monitoring of Respiratory Virus Infection in Solid Organ Transplant Recipients,http://dx.doi.org/10.1016/j.jcv.2014.10.021,PMC4629250,,,"BACKGROUND: Methods for the longitudinal study of respiratory virus infections are cumbersome and limit our understanding of the natural history of these infections in solid organ transplant (SOT) recipients. OBJECTIVES: To assess the feasibility and patient acceptability of self-collected foam nasal swabs for detection of respiratory viruses in SOT recipients and to define the virologic and clinical course. STUDY DESIGN: We prospectively monitored the course of symptomatic respiratory virus infection in 18 SOT patients (14 lung, 3 liver, and 1 kidney) using patient self-collected swabs. RESULTS: The initial study sample was positive in 15 patients with the following respiratory viruses: rhinovirus (6), metapneumovirus (1), coronavirus (2), respiratory syncytial virus (2), parainfluenza virus (2), and influenza A virus (2). One hundred four weekly self-collected nasal swabs were obtained, with a median of 4 samples per patient (range 1–17). Median duration of viral detection was 21 days (range 4–77 days). Additional new respiratory viruses detected during follow-up of these 15 patients included rhinovirus (3), metapneumovirus (2), coronavirus (1), respiratory syncytial virus (1), parainfluenza virus (1), and adenovirus (1). Specimen collection compliance was good; 16/18 (89%) patients collected all required specimens and 79/86 (92%) follow-up specimens were obtained within the 7±3 day protocol-defined window. All participants agreed or strongly agreed that the procedure was comfortable, simple, and 13/14 (93%) were willing to participate in future studies using this procedure. CONCLUSION: Self-collected nasal swabs provide a convenient, feasible, and patient-acceptable methodology for longitudinal monitoring of upper respiratory virus infection in SOT recipients.",,"['Preiksaitis, Carl M.', 'Kuypers, Jane M.', 'Fisher, Cynthia E.', 'Campbell, Angela P.', 'Jerome, Keith R.', 'Huang, Meei-Li', 'Boeckh, Michael', 'Limaye, Ajit P.']",,,,
,PMC,Wongabel Rhabdovirus Accessory Protein U3 Targets the SWI/SNF Chromatin Remodeling Complex,http://dx.doi.org/10.1128/JVI.02010-14,PMC4300651,,,"Wongabel virus (WONV) is an arthropod-borne rhabdovirus that infects birds. It is one of the growing array of rhabdoviruses with complex genomes that encode multiple accessory proteins of unknown function. In addition to the five canonical rhabdovirus structural protein genes (N, P, M, G, and L), the 13.2-kb negative-sense single-stranded RNA (ssRNA) WONV genome contains five uncharacterized accessory genes, one overlapping the N gene (Nx or U4), three located between the P and M genes (U1 to U3), and a fifth one overlapping the G gene (Gx or U5). Here we show that WONV U3 is expressed during infection in insect and mammalian cells and is required for efficient viral replication. A yeast two-hybrid screen against a mosquito cell cDNA library identified that WONV U3 interacts with the 83-amino-acid (aa) C-terminal domain of SNF5, a component of the SWI/SNF chromatin remodeling complex. The interaction was confirmed by affinity chromatography, and nuclear colocalization was established by confocal microscopy. Gene expression studies showed that SNF5 transcripts are upregulated during infection of mosquito cells with WONV, as well as West Nile virus (Flaviviridae) and bovine ephemeral fever virus (Rhabdoviridae), and that SNF5 knockdown results in increased WONV replication. WONV U3 also inhibits SNF5-regulated expression of the cytokine gene CSF1. The data suggest that WONV U3 targets the SWI/SNF complex to block the host response to infection. IMPORTANCE The rhabdoviruses comprise a large family of RNA viruses infecting plants, vertebrates, and invertebrates. In addition to the major structural proteins (N, P, M, G, and L), many rhabdoviruses encode a diverse array of accessory proteins of largely unknown function. Understanding the role of these proteins may reveal much about host-pathogen interactions in infected cells. Here we examine accessory protein U3 of Wongabel virus, an arthropod-borne rhabdovirus that infects birds. We show that U3 enters the nucleus and interacts with SNF5, a component of the chromatin remodeling complex that is upregulated in response to infection and restricts viral replication. We also show that U3 inhibits SNF5-regulated expression of the cytokine colony-stimulating factor 1 (CSF1), suggesting that it targets the chromatin remodeling complex to block the host response to infection. This study appears to provide the first evidence of a virus targeting SNF5 to inhibit host gene expression.",,"['Joubert, D. Albert', 'Rodriguez-Andres, Julio', 'Monaghan, Paul', 'Cummins, Michelle', 'McKinstry, William J.', 'Paradkar, Prasad N.', 'Moseley, Gregory W.', 'Walker, Peter J.']",,,,
,PMC,Garlic for the common cold,http://dx.doi.org/10.1002/14651858.CD006206.pub4,PMC6465033,,,"BACKGROUND: Garlic is alleged to have antimicrobial and antiviral properties that relieve the common cold, among other beneficial effects. There is widespread usage of garlic supplements. The common cold is associated with significant morbidity and economic consequences. On average, children have six to eight colds per year and adults have two to four. OBJECTIVES: To determine whether garlic (Allium sativum) is effective for the prevention or treatment of the common cold, when compared to placebo, no treatment or other treatments. SEARCH METHODS: We searched CENTRAL (2014, Issue 7), OLDMEDLINE (1950 to 1965), MEDLINE (January 1966 to July week 5, 2014), EMBASE (1974 to August 2014) and AMED (1985 to August 2014). SELECTION CRITERIA: Randomised controlled trials of common cold prevention and treatment comparing garlic with placebo, no treatment or standard treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed and selected trials from searches, assessed and rated study quality and extracted relevant data. MAIN RESULTS: In this updated review, we identified eight trials as potentially relevant from our searches. Again, only one trial met the inclusion criteria. This trial randomly assigned 146 participants to either a garlic supplement (with 180 mg of allicin content) or a placebo (once daily) for 12 weeks. The trial reported 24 occurrences of the common cold in the garlic intervention group compared with 65 in the placebo group (P value < 0.001), resulting in fewer days of illness in the garlic group compared with the placebo group (111 versus 366). The number of days to recovery from an occurrence of the common cold was similar in both groups (4.63 versus 5.63). Only one trial met the inclusion criteria, therefore limited conclusions can be drawn. The trial relied on self reported episodes of the common cold but was of reasonable quality in terms of randomisation and allocation concealment. Adverse effects included rash and odour. AUTHORS' CONCLUSIONS: There is insufficient clinical trial evidence regarding the effects of garlic in preventing or treating the common cold. A single trial suggested that garlic may prevent occurrences of the common cold but more studies are needed to validate this finding. Claims of effectiveness appear to rely largely on poor‐quality evidence.",,"['Lissiman, Elizabeth', 'Bhasale, Alice L', 'Cohen, Marc']",,,,
,PMC,Infiltrating regulatory B-cells control neuroinflammation following viral brain infection,http://dx.doi.org/10.4049/jimmunol.1400654,PMC4258482,,,"Previous studies have demonstrated the existence of a subset of B lymphocytes, regulatory B-cells (Bregs), which modulate immune function. Here, in vivo and in vitro experiments were undertaken to elucidate the role of these Bregs in controlling neuroinflammation following viral brain infection. We used multi-color flow cytometry to phenotype lymphocyte subpopulations infiltrating the brain, along with in vitro co-cultures to assess their anti-inflammatory and immunoregulatory roles. This distinctive subset of CD19(+)CD1d(hi)CD5(+) B-cells was found to infiltrate the brains of chronically infected animals, reaching highest levels at the latest time point tested (30 d p.i.). B-cell-deficient Jh(−/−) mice were found to develop exacerbated neuroimmune responses as measured by enhanced accumulation and/or retention of CD8(+) T-cells within the brain, as well as increased levels of microglial activation (MHC class II). Conversely, levels of Foxp3(+) regulatory T-cells (Tregs) were found to be significantly lower in Jh(−/−) mice when compared to wild-type (Wt) animals. Further experiments showed that in vitro generated IL-10-secreting regulatory B-cells (B10) were able to inhibit cytokine responses from microglia following stimulation with viral antigens. These in vitro generated B10 cells were also found to promote proliferation of regulatory T-cells in co-culture studies. Finally, gain of function experiments demonstrated that reconstitution of Wt B-cells into Jh(−/−) mice restored neuroimmune responses to levels exhibited by infected Wt mice. Taken together, these results demonstrate that regulatory B-cells modulate T lymphocyte as well as microglial cell responses within the infected brain and promote CD4(+)Foxp3(+) T-cell proliferation in vitro.",,"['Mutnal, Manohar B.', 'Hu, Shuxian', 'Schachtele, Scott J.', 'Lokensgard, James R.']",,,,
,PMC,Primate lentiviruses are differentially inhibited by interferon-induced transmembrane proteins,http://dx.doi.org/10.1016/j.virol.2014.10.015,PMC4581848,,,"Interferon-induced transmembrane (IFITM) proteins inhibit the entry of a large number of viruses. Not surprisingly, many viruses are refractory to this inhibition. In this study, we report that different strains of HIV and SIV are inhibited by human IFITM proteins to various degrees, with SIV of African green monkeys (SIV(AGM)) being mostly restricted by human IFITM2. Interestingly, SIV(AGM) is as much inhibited by human IFITM2 as by IFITM3 of its own host African green monkeys. Our data further demonstrate that the entry of SIV(AGM) is impaired by human IFITM2 and that this inhibition is overcome by the cholesterol-binding compound amphotericin B that also overcomes IFITM inhibition of influenza A viruses. These results suggest that IFITM proteins exploit similar mechanisms to inhibit the entry of both pH-independent primate lentiviruses and the pH-dependent influenza A viruses.",,"['Qian, Jin', 'Le Duff, Yann', 'Wang, Yimeng', 'Pan, Qinghua', 'Ding, Shilei', 'Zheng, Yi-Min', 'Liu, Shan-Lu', 'Liang, Chen']",,,,
,PMC,Structural Dynamics as a Contributor to Error-prone Replication by an RNA-dependent RNA Polymerase,http://dx.doi.org/10.1074/jbc.M114.616193,PMC4276885,,,"RNA viruses encoding high- or low-fidelity RNA-dependent RNA polymerases (RdRp) are attenuated. The ability to predict residues of the RdRp required for faithful incorporation of nucleotides represents an essential step in any pipeline intended to exploit perturbed fidelity as the basis for rational design of vaccine candidates. We used x-ray crystallography, molecular dynamics simulations, NMR spectroscopy, and pre-steady-state kinetics to compare a mutator (H273R) RdRp from poliovirus to the wild-type (WT) enzyme. We show that the nucleotide-binding site toggles between the nucleotide binding-occluded and nucleotide binding-competent states. The conformational dynamics between these states were enhanced by binding to primed template RNA. For the WT, the occluded conformation was favored; for H273R, the competent conformation was favored. The resonance for Met-187 in our NMR spectra reported on the ability of the enzyme to check the correctness of the bound nucleotide. Kinetic experiments were consistent with the conformational dynamics contributing to the established pre-incorporation conformational change and fidelity checkpoint. For H273R, residues comprising the active site spent more time in the catalytically competent conformation and were more positively correlated than the WT. We propose that by linking the equilibrium between the binding-occluded and binding-competent conformations of the nucleotide-binding pocket and other active-site dynamics to the correctness of the bound nucleotide, faithful nucleotide incorporation is achieved. These studies underscore the need to apply multiple biophysical and biochemical approaches to the elucidation of the physical basis for polymerase fidelity.",,"['Moustafa, Ibrahim M.', 'Korboukh, Victoria K.', 'Arnold, Jamie J.', 'Smidansky, Eric D.', 'Marcotte, Laura L.', 'Gohara, David W.', 'Yang, Xiaorong', 'Sánchez-Farrán, María Antonieta', 'Filman, David', 'Maranas, Janna K.', 'Boehr, David D.', 'Hogle, James M.', 'Colina, Coray M.', 'Cameron, Craig E.']",,,,
,PMC,Human Rhinovirus C Infections in Pediatric Hematology and Oncology Patients,http://dx.doi.org/10.1111/petr.12383,PMC4280346,,,"BACKGROUND: Children with cancer and hematopoietic stem cell transplant (HSCT) recipients are at high risk for common viral infections. We sought to define the viral etiology of acute respiratory infections (ARI) and identify risk factors. METHODS: Nasal wash samples were collected from pediatric hematology-oncology patients and HSCT recipients with ARI during the 2003–2005 winter seasons. Real-time RT-PCR was performed to detect influenza A (Flu A), influenza B, respiratory syncytial virus (RSV), parainfluenzaviruses (PIV) 1–3, human metapneumovirus (MPV), and human rhinoviruses (HRV). HRV specimens were sequenced and genotyped. RESULTS: Seventy-eight samples from 62 children were included. Viruses were detected in 31 of 78 samples (40%). HRV were detected most frequently, in 16 (52%) including 5 HRV type C (HRVC); followed by 7 (22%) RSV, 5 (16%) Flu A, 4 (13%) MPV and 2 (6%) PIV2. There was a trend toward higher risk of viral infection for children in daycare. Only 8% of the study children had received infuenza vaccine. CONCLUSIONS: HRV, including the recently discovered HRVC, are an important cause of infection in pediatric oncology and HSCT patients. Molecular testing is superior to conventional methods and should be standard of care, since HRV are not detected by conventional methods.",,"['Loria, Carolina', 'Domm, Jennifer A.', 'Halasa, Natasha B.', 'Heitman, Elizabeth', 'Miller, E. Kathryn', 'Xu, Meng', 'Saville, Benjamin R.', 'Frangoul, Haydar', 'Williams, John V.']",,,,
,PMC,Rotavirus Entry: a Deep Journey into the Cell with Several Exits,http://dx.doi.org/10.1128/JVI.01787-14,PMC4300671,,,"Rotaviruses are the leading etiological agents of acute gastroenteritis in infants and young children worldwide. These nonenveloped viruses enter cells using different types of endocytosis and, depending on the virus strain, travel to different endosomal compartments before exiting to the cytosolic space. In this Gem, we review the viral and cellular factors involved in the different stages of a productive virus cell entry and share with the readers the journey that we have taken into the cell to learn about virus entry.",,"['Arias, Carlos F.', 'Silva-Ayala, Daniela', 'López, Susana']",,,,
,PMC,Activation of the Chicken Type I Interferon Response by Infectious Bronchitis Coronavirus,http://dx.doi.org/10.1128/JVI.02671-14,PMC4300645,,,"Coronaviruses from both the Alphacoronavirus and Betacoronavirus genera interfere with the type I interferon (IFN) response in various ways, ensuring the limited activation of the IFN response in most cell types. Of the gammacoronaviruses that mainly infect birds, little is known about the activation of the host immune response. We show that the prototypical Gammacoronavirus, infectious bronchitis virus (IBV), induces a delayed activation of the IFN response in primary renal cells, tracheal epithelial cells, and a chicken cell line. In fact, Ifnβ expression is delayed with respect to the peak of viral replication and the accompanying accumulation of double-stranded RNA (dsRNA). In addition, we demonstrate that MDA5 is the primary sensor for Gammacoronavirus infections in chicken cells. Furthermore, we provide evidence that accessory proteins 3a and 3b of IBV modulate the response at the transcriptional and translational levels. Finally, we show that, despite the lack of activation of the IFN response during the early phase of IBV infection, the signaling of nonself dsRNA through both MDA5 and TLR3 remains intact in IBV-infected cells. Taken together, this study provides the first comprehensive analysis of host-virus interactions of a Gammacoronavirus with avian innate immune responses. IMPORTANCE Our results demonstrate that IBV has evolved multiple strategies to avoid the activation of the type I interferon response. Taken together, the present study closes a gap in the understanding of host-IBV interaction and paves the way for further characterization of the mechanisms underlying immune evasion strategies as well as the pathogenesis of gammacoronaviruses.",,"['Kint, Joeri', 'Fernandez-Gutierrez, Marcela', 'Maier, Helena J.', 'Britton, Paul', 'Langereis, Martijn A.', 'Koumans, Joseph', 'Wiegertjes, Geert F.', 'Forlenza, Maria']",,,,
,PMC,Epitope Identification from Fixed-complexity Random-sequence Peptide Microarrays,http://dx.doi.org/10.1074/mcp.M114.043513,PMC4288249,,,"Antibodies play an important role in modern science and medicine. They are essential in many biological assays and have emerged as an important class of therapeutics. Unfortunately, current methods for mapping antibody epitopes require costly synthesis or enrichment steps, and no low-cost universal platform exists. In order to address this, we tested a random-sequence peptide microarray consisting of over 330,000 unique peptide sequences sampling 83% of all possible tetramers and 27% of pentamers. It is a single, unbiased platform that can be used in many different types of tests, it does not rely on informatic selection of peptides for a particular proteome, and it does not require iterative rounds of selection. In order to optimize the platform, we developed an algorithm that considers the significance of k-length peptide subsequences (k-mers) within selected peptides that come from the microarray. We tested eight monoclonal antibodies and seven infectious disease cohorts. The method correctly identified five of the eight monoclonal epitopes and identified both reported and unreported epitope candidates in the infectious disease cohorts. This algorithm could greatly enhance the utility of random-sequence peptide microarrays by enabling rapid epitope mapping and antigen identification.",,"['Richer, Josh', 'Johnston, Stephen Albert', 'Stafford, Phillip']",,,,
,PMC,"Investigating an outbreak of acute fever in Chuuk, Federated States of Micronesia",http://dx.doi.org/10.5365/WPSAR.2014.5.3.005,PMC4318975,,,"OBJECTIVE: In September 2012, there was an unexpected increase of acute febrile illness (AFI) in Chuuk State of the Federated States of Micronesia. At the same time, dengue outbreaks were occurring in two of the Federated States of Micronesia’s other three states. The cause of AFI was suspected to be dengue; however, by the end of October, only one of 39 samples was positive for dengue. The objective of the investigation was to establish the cause of the outbreak. METHODS: A line list was created and data analysed by time, place, person and clinical features. Reported symptoms were compared with the published symptoms of several diagnoses and laboratory testing undertaken. RESULTS: Of the 168 suspected cases, 62% were less than 20 years of age and 60% were male. The clinical features of the cases were not typical for dengue but suggestive of respiratory illness. Nasopharyngeal swabs were subsequently collected and found to be positive for influenza. Public health measures were undertaken and the AFI returned to expected levels. DISCUSSION: Clinical diagnosis of acute febrile illness (AFI) can often be difficult and misleading. This can mean that opportunities for preventive measures early on in an outbreak are missed. In any outbreak, descriptive epidemiological analyses are valuable in helping to ascertain the cause of the outbreak.",,"['Hoy, Damian', 'Yichiro, Yoster', 'Otoko, Kasian', 'Heldart, Helden', 'Meyshine, Andita', 'Assito, Prisca', 'Pretrick, Moses', 'Souares, Yvan', 'Hancock, Thane', 'Durand, Mark', 'Roth, Adam']",,,,
,PMC,Cytoplasmic RNA Granules and Viral Infection,http://dx.doi.org/10.1146/annurev-virology-031413-085505,PMC4867093,,,"RNA granules are dynamic cellular structures essential for proper gene expression and homeostasis. The two principle types of cytoplasmic RNA granules are stress granules (SGs), which contain stalled translation initiation complexes, and processing bodies (P-bodies, PBs), which concentrate factors involved in mRNA degradation. RNA granules are associated with gene silencing of transcripts, thus, viruses repress RNA granule functions to favor replication. This review discusses the breadth of viral interactions with cytoplasmic RNA granules, focusing on mechanisms that modulate the functions of RNA granules and that typically promote viral replication. Currently mechanisms for virus manipulation of RNA granules can be loosely grouped into three non-exclusive categories; i) cleavage of key RNA granule factors, ii) regulation of PKR activation and iii) co-opting RNA granule factors for new roles in viral replication. Viral repression of RNA granules supports productive infection by inhibiting their gene silencing functions and counteracting their role in linking stress sensing with innate immune activation.",,"['Tsai, Wei-Chih', 'Lloyd, Richard E.']",,,,
,PMC,IFITM-Family Proteins: The Cell’s First Line of Antiviral Defense,http://dx.doi.org/10.1146/annurev-virology-031413-085537,PMC4295558,,,"Animal cells use a wide variety of mechanisms to slow or prevent replication of viruses. These mechanisms are usually mediated by antiviral proteins whose expression and activities can be constitutive but are frequently amplified by interferon induction. Among these interferon-stimulated proteins, members of the IFITM (interferon-induced transmembrane) family are unique because they prevent infection before a virus can traverse the lipid bilayer of the cell. At least three human IFITM proteins—IFITM1, IFITM2, and IFITM3—have antiviral activities. These activities limit infection in cultured cells by many viruses, including dengue virus, Ebola virus, influenza A virus, severe acute respiratory syndrome coronavirus, and West Nile virus. Murine Ifitm3 controls influenza A virus infection in vivo, and polymorphisms in human IFITM3 correlate with the severity of both seasonal and highly pathogenic avian influenza virus. Here we review the discovery and characterization of the IFITM proteins, describe the spectrum of their antiviral activities, and discuss potential mechanisms underlying these effects.",,"['Bailey, Charles C.', 'Zhong, Guocai', 'Huang, I-Chueh', 'Farzan, Michael']",,,,
,PMC,Primary immune-mediated neutropenia in a cat,,PMC4204839,,,"An 18-month-old male castrated indoor Himalayan cat was presented for recurrent fever, lethargy, and uveitis. Persistent neutropenia was identified and tests for infectious disease and bone marrow cytology were performed. Primary immune-mediated neutropenia was diagnosed and successfully treated. At the time of writing this report, 24 mo after the initial diagnosis. the patient was clinically normal and not receiving therapy.",,"['Waugh, Carly E.', 'Scott, Katherine D.', 'Bryan, Laura K.']",,,,
,PMC,Canada: Porcine epidemic diarrhea in Canada: An emerging disease case study,,PMC4204834,,,,,"Kochhar, Harpreet S.",,,,
,PMC,"Use of S-[2,3-Bispalmitoyiloxy-(2R)-Propyl]-R-Cysteinyl-Amido-Monomethoxy Polyethylene Glycol as an Adjuvant Improved Protective Immunity Associated with a DNA Vaccine Encoding Cu,Zn Superoxide Dismutase of Brucella abortus in Mice",http://dx.doi.org/10.1128/CVI.00554-14,PMC4248768,,,"This study was conducted to evaluate the immunogenicity and protective efficacy of a DNA vaccine encoding Brucella abortus Cu,Zn superoxide dismutase (SOD) using the Toll-like receptor 2/6 agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxy polyethylene glycol (BPPcysMPEG) as an adjuvant. Intranasal coadministration of BPPcysMPEG with a plasmid carrying the SOD-encoding gene (pcDNA-SOD) into BALB/c mice elicited antigen-specific humoral and cellular immune responses. Humoral responses were characterized by the stimulation of IgG2a and IgG1 and by the presence of SOD-specific secretory IgA in nasal and bronchoalveolar lavage fluids. Furthermore, T-cell proliferative responses and increased production of gamma interferon were also observed upon splenocyte restimulation with recombinant SOD. Cytotoxic responses were also stimulated, as demonstrated by the lysis of RB51-SOD-infected J774.A1 macrophages by cells recovered from immunized mice. The pcDNA-SOD/BPPcysMPEG formulation induced improved protection against challenge with the virulent strain B. abortus 2308 in BALB/c mice over that provided by pcDNA-SOD, suggesting the potential of this vaccination strategy against Brucella infection.",,"['Retamal-Díaz, Angello', 'Riquelme-Neira, Roberto', 'Sáez, Darwin', 'Rivera, Alejandra', 'Fernández, Pablo', 'Cabrera, Alex', 'Guzmán, Carlos A.', 'Oñate, Ángel']",,,,
,PMC,Utilization of Viral Molecular Diagnostics Among Children Hospitalized With Community Acquired Pneumonia,http://dx.doi.org/10.1542/hpeds.2014-0018,PMC4269521,,,"OBJECTIVE: To examine whether results of a polymerase chain reaction–based respiratory viral panel (RVP) are associated with changes in antibiotic use or differential clinical outcomes among children hospitalized with pneumonia. METHODS: We retrospectively identified otherwise healthy children hospitalized over a 3-year period at a single institution with community-acquired pneumonia who had an RVP performed within 24 hours of admission. We examined associations between RVP results and clinical outcomes as well as management decisions including initiation and duration of intravenous antibiotics. RESULTS: Among 202 children, a positive RVP (n = 127, 63%) was associated with a more complicated clinical course, although this was due largely to more severe disease seen in younger children and those with respiratory syncytial virus (n = 38, 30% of positive detections). Detection of a virus did not influence antibiotic therapy. Included children were younger and had more severe illness than children hospitalized with pneumonia at the same institution without an RVP obtained. CONCLUSIONS: In our study, only respiratory syncytial virus was associated with a more severe clinical course compared with RVP-negative children. Regardless of the virus detected, RVP positivity did not influence antibiotic usage. However, RVP use focused primarily on children with severe pneumonia. Whether similar testing influences management decisions among children with less severe illness deserves further study.",,"['Schulert, Grant S.', 'Hain, Paul D.', 'Williams, Derek J.']",,,,
,PMC,Development of a heat-stable and orally delivered recombinant M2e-expressing B. subtilis spore-based influenza vaccine,http://dx.doi.org/10.4161/hv.36122,PMC4514050,,,"Highly conserved ectodomain of influenza virus M2 protein (M2e) is an important target for the development of universal influenza vaccines. Today, the use of chemical or genetic fusion constructs have been undertaken to overcome the low immunogenicity of M2e in vaccine formulation. However, current M2e vaccines are neither orally delivered nor heat-stable. In this study, we evaluated the immune efficacy of an orally delivered recombinant M2e vaccine containing 3 molcules of M2e consensus sequence of influenza A viruses, termed RSM2e3. To accomplish this, CotB, a spore coat of Bacillus subtilis (B. subtilis), was used as a fusion partner, and heat-stable nonpathogenic B. subtilis spores were used as the carrier. Our results showed that CotB-M2e3 fusion had no effect on spore structure or function in the resultant recombinant RSM2e3 strain and that heterologous influenza virus M2e protein was successfully displayed on the surface of the recombinant RSM2e3 spore. Importantly, recombinant RSM2e3 spores elicited strong and long-term M2e-specific systemic and mucosal immune responses, completely protecting immunized mice from lethal challenge of A/PR/8/34(H1N1) influenza virus. Taken together, our study forms a solid basis for the development of a novel orally delivered and heat-stable influenza vaccine based on B. subtilis spore surface display.",,"['Zhao, Guangyu', 'Miao, Yu', 'Guo, Yan', 'Qiu, Hongjie', 'Sun, Shihui', 'Kou, Zhihua', 'Yu, Hong', 'Li, Junfeng', 'Chen, Yue', 'Jiang, Shibo', 'Du, Lanying', 'Zhou, Yusen']",,,,
,PMC,Characterization of Rat Pinworm (Syphacia muris) Epidemiology as a Means to Increase Detection and Elimination,,PMC4253580,,,"Rodent pinworms persist in many institutions, suggesting deficiencies in eradication and diagnostic processes. When pinworms are detected, treatment success is common, but false-negative test results during health surveillance or after treatment likely contribute to the continued presence of this parasite. PCR testing is not always practical, and increased information regarding the life cycle and general epidemiology of pinworm infestations could improve the sensitivity of traditional nonPCR detection methods and improve eradication efforts. We therefore investigated a pinworm (Syphacia muris) infestation in Sprague–Dawley rats (Rattus norvegicus) to develop a more accurate testing strategy. In addition, we sought to determine the duration of egg viability by using an in vitro hatching protocol to assess environmental persistence. Finally, we tested the ovicidal efficacy of a disinfectant used at our institution. Eggs were shed in higher numbers in the midafternoon as compared with other times of the day, and the sex of the host had no consistent effect on egg shedding. Egg shedding showed periodicity over time, with shedding decreasing to 0 at 2- to 3-wk intervals. Neither cecal examination nor tape tests alone reliably predicted pinworm infestation, and results of the 2 tests did not necessarily coincide. Eggs aged for as long as 7 mo remained viable, indicating a potential for recontamination from the environment. Finally, gaseous chlorine dioxide was an effective ovicidal agent, with a kill rate of 99.7%. These results suggest that strategies for S. muris eradication can be optimized to increase detection and elimination.",,"['Meade, Theresa M', 'Watson, Julie']",,,,
,PMC,Predictive Value of Testing Nasopharyngeal Samples for Respiratory Viruses in the Setting of Lower Respiratory Tract Disease,http://dx.doi.org/10.1128/JCM.01944-14,PMC4313242,,,"To determine the predictive value of nasopharyngeal (NP) sample testing for respiratory viruses (RVs) in suspected lower respiratory tract disease, 72 paired NP and bronchoalveolar lavage (BAL) fluid specimen sets, mostly from transplant recipients or patients with hematologic malignancies, were analyzed. Overall, 31.3% of the specimens tested positive for an RV. In 19 sets (26.4%), the NP and BAL fluid specimens were both positive for an RV; in 3 sets (4.2%), the NP specimens were positive but the BAL fluid specimens were negative; and in 3 other sets, the NP specimens were negative but the BAL fluid specimens were positive. The positive and negative predictive values of the NP specimens were 86.4% and 94%, respectively.",,"['Hakki, Morgan', 'Strasfeld, Lynne M.', 'Townes, John M.']",,,,
,PMC,Faecal virome of cats in an animal shelter,http://dx.doi.org/10.1099/vir.0.069674-0,PMC4202271,,,"We describe the metagenomics-derived feline enteric virome in the faeces of 25 cats from a single shelter in California. More than 90 % of the recognizable viral reads were related to mammalian viruses and the rest to bacterial viruses. Eight viral families were detected: Astroviridae, Coronaviridae, Parvoviridae, Circoviridae, Herpesviridae, Anelloviridae, Caliciviridae and Picobirnaviridae. Six previously known viruses were also identified: feline coronavirus type 1, felid herpes 1, feline calicivirus, feline norovirus, feline panleukopenia virus and picobirnavirus. Novel species of astroviruses and bocaviruses, and the first genome of a cyclovirus in a feline were characterized. The RNA-dependent RNA polymerase region from four highly divergent partial viral genomes in the order Picornavirales were sequenced. The detection of such a diverse collection of viruses shed within a single shelter suggested that such animals experience robust viral exposures. This study increases our understanding of the viral diversity in cats, facilitating future evaluation of their pathogenic and zoonotic potentials.",,"['Zhang, Wen', 'Li, Linlin', 'Deng, Xutao', 'Kapusinszky, Beatrix', 'Pesavento, Patricia A.', 'Delwart, Eric']",,,,
,PMC,IFN-λ4: The Paradoxical New Member of the Interferon Lambda Family,http://dx.doi.org/10.1089/jir.2013.0136,PMC4217005,,,"Interferons (IFNs) are generally considered antiviral cytokines, yet the newly discovered IFN-λ4 is linked with the failure to clear hepatitis C virus (HCV) infection either spontaneously or in response to treatment. IFN-λ4 can be generated only by individuals who carry the IFNL4-ΔG allele (rs368234815), which is the strongest known host factor for predicting clearance of HCV. The ancestral IFNL4-ΔG allele is the major variant in Africans while the minor variant in Asians, suggesting very strong negative genetic selection for this allele—most likely driven by an infectious agent other than HCV. IFN-λ4 most closely resembles IFN-λ3, but these proteins share only 29% amino-acid identity, and, in contrast to IFN-λ3, IFN-λ4 is only weakly secreted. Nevertheless, IFN-λ4 signals through the IFN-λ receptor complex and induces expression of IFN-stimulated genes via the Janus kinase-signal transducer and activator of transcription signaling pathway. Although the IFNL4-ΔG variant is strongly associated with the failure to clear HCV infection, HCV-infected patients who carry this allele have lower baseline HCV RNA levels in the absence of treatment. Resolving the paradoxical functions of IFN-λ4, which appears to induce antiviral activity yet impair effective clearance of HCV, may yield critical new insights into the immunologic response to HCV infection and IFN biology.",,"[""O'Brien, Thomas R."", 'Prokunina-Olsson, Ludmila', 'Donnelly, Raymond P.']",,,,
,PMC,Human Coronavirus NL63 Utilizes Heparan Sulfate Proteoglycans for Attachment to Target Cells,http://dx.doi.org/10.1128/JVI.02078-14,PMC4249106,,,"Human coronavirus NL63 (HCoV-NL63) is an alphacoronavirus that was first identified in 2004 in the nasopharyngeal aspirate from a 7-month-old patient with a respiratory tract infection. Previous studies showed that HCoV-NL63 and the genetically distant severe acute respiratory syndrome (SARS)-CoV employ the same receptor for host cell entry, angiotensin-converting enzyme 2 (ACE2), but it is largely unclear whether ACE2 interactions are sufficient to allow HCoV-NL63 binding to cells. The present study showed that directed expression of angiotensin-converting enzyme 2 (ACE2) on cells previously resistant to HCoV-NL63 renders them susceptible, showing that ACE2 protein acts as a functional receptor and that its expression is required for infection. However, comparative analysis showed that directed expression or selective scission of the ACE2 protein had no measurable effect on virus adhesion. In contrast, binding of HCoV-NL63 to heparan sulfates was required for viral attachment and infection of target cells, showing that these molecules serve as attachment receptors for HCoV-NL63. IMPORTANCE ACE2 protein was proposed as a receptor for HCoV-NL63 already in 2005, but an in-depth analysis of early events during virus infection had not been performed thus far. Here, we show that the ACE2 protein is required for viral entry but that it is not the primary binding site on the cell surface. Conducted research showed that heparan sulfate proteoglycans function as adhesion molecules, increasing the virus density on cell surface and possibly facilitating the interaction between HCoV-NL63 and its receptor. Obtained results show that the initial events during HCoV-NL63 infection are more complex than anticipated and that a newly described interaction may be essential for understanding the infection process and, possibly, also assist in drug design.",,"['Milewska, Aleksandra', 'Zarebski, Miroslaw', 'Nowak, Paulina', 'Stozek, Karol', 'Potempa, Jan', 'Pyrc, Krzysztof']",,,,
,PMC,"Entry of a Novel Marine DNA Virus, Singapore Grouper Iridovirus, into Host Cells Occurs via Clathrin-Mediated Endocytosis and Macropinocytosis in a pH-Dependent Manner",http://dx.doi.org/10.1128/JVI.01744-14,PMC4249105,,,"Iridoviruses are nucleocytoplasmic DNA viruses which cause great economic losses in the aquaculture industry but also show significant threat to global biodiversity. However, a lack of host cells has resulted in poor progress in clarifying iridovirus behavior. We investigated the crucial events during virus entry using a combination of single-virus tracking and biochemical assays, based on the established virus-cell infection model for Singapore grouper iridovirus (SGIV). SGIV infection in host cells was strongly inhibited when cells were pretreated with drugs blocking clathrin-mediated endocytosis, including sucrose and chlorpromazine. Inhibition of key regulators of macropinocytosis, including Na(+)/H(+) exchanger, Rac1 GTPase, p21-activated kinase 1 (PAK1), protein kinase C (PKC), and myosin II, significantly reduced SGIV uptake. Cy5-labeled SGIV particles were observed to colocalize with clathrin and macropinosomes. In contrast, disruption of cellular cholesterol by methyl-β-cyclodextrin and nystatin had no effect on virus infection, suggesting that SGIV entered grouper cells via the clathrin-mediated endocytic pathway and macropinocytosis but not via caveola-dependent endocytosis. Furthermore, inhibitors of endosome acidification such as chloroquine and bafilomycin A1 blocked virus infection, indicating that SGIV entered cells in a pH-dependent manner. In addition, SGIV particles were observed to be transported along both microtubules and actin filaments, and intracellular SGIV motility was remarkably impaired by depolymerization of microtubules or actin filaments. The results of this study for the first time demonstrate that not only the clathrin-dependent pathway but also macropinocytosis are involved in fish DNA enveloped virus entry, thus providing a convenient tactic for exploring the life cycle of DNA viruses. IMPORTANCE Virus entry into host cells is critically important for initiating infections and is usually recognized as an ideal target for the design of antiviral strategies. Iridoviruses are large DNA viruses which cause serious threats to ecological diversity and the aquaculture industry worldwide. However, the current understanding of iridovirus entry is limited and controversial. Singapore grouper iridovirus (SGIV) is a novel marine fish DNA virus which belongs to genus Ranavirus, family Iridoviridae. Here, using single-virus tracking technology in combination with biochemical assays, we investigated the crucial events during SGIV entry and demonstrated that SGIV entered grouper cells via the clathrin-mediated endocytic pathway in a pH-dependent manner but not via caveola-dependent endocytosis. Furthermore, we propose for the first time that macropinocytosis is involved in iridovirus entry. Together, this work not only contributes greatly to understating iridovirus pathogenesis but also provides an ideal model for exploring the behavior of DNA viruses in living cells.",,"['Wang, Shaowen', 'Huang, Xiaohong', 'Huang, Youhua', 'Hao, Xian', 'Xu, Haijiao', 'Cai, Mingjun', 'Wang, Hongda', 'Qin, Qiwei']",,,,
,PMC,Stepwise Priming by Acidic pH and a High K(+) Concentration Is Required for Efficient Uncoating of Influenza A Virus Cores after Penetration,http://dx.doi.org/10.1128/JVI.01430-14,PMC4249060,,,"Influenza A virus (IAV) uses the low pH in late endocytic vacuoles as a cue for penetration by membrane fusion. Here, we analyzed the prefusion reactions that prepare the core for uncoating after it has been delivered to the cytosol. We found that this priming process occurs in two steps that are mediated by the envelope-embedded M2 ion channel. The first weakens the interactions between the matrix protein, M1, and the viral ribonucleoprotein bundle. It involves a conformational change in a linker sequence and the C-terminal domain of M1 after exposure to a pH below 6.5. The second step is triggered by a pH of <6.0 and by the influx of K(+) ions. It causes additional changes in M1 as well as a loss of stability in the viral ribonucleoprotein bundle. Our results indicate that both the switch from Na(+) to K(+) in maturing endosomes and the decreasing pH are needed to prime IAV cores for efficient uncoating and infection of the host cell. IMPORTANCE The entry of IAV involves several steps, including endocytosis and fusion at late endosomes. Entry also includes disassembly of the viral core, which is composed of the viral ribonucleoproteins and the RNA genome. We have found that the uncoating process of IAV is initiated long before the core is delivered into the cytosol. M2, an ion channel in the viral membrane, is activated when the virus passes through early endosomes. Here, we show that protons entering the virus through M2 cause a conformational change in the matrix protein, M1. This weakens interactions between M1 and the viral ribonucleoproteins. A second change was found to occur when the virus enters late endosomes. The preacidified core is then exposed to a high concentration of K(+), which affects the interactions between the ribonucleoproteins. Thus, when cores are finally delivered to the cytosol, they are already partially destabilized and, therefore, uncoating competent and infectious.",,"['Stauffer, Sarah', 'Feng, Yuehan', 'Nebioglu, Firat', 'Heilig, Rosalie', 'Picotti, Paola', 'Helenius, Ari']",,,,
,PMC,The Endoplasmic Reticulum Stress Sensor IRE1α Protects Cells from Apoptosis Induced by the Coronavirus Infectious Bronchitis Virus,http://dx.doi.org/10.1128/JVI.02138-14,PMC4248946,,,"The unfolded-protein response (UPR) is a signal transduction cascade triggered by perturbation of the homeostasis of the endoplasmic reticulum (ER). UPR resolves ER stress by activating a cascade of cellular responses, including the induction of molecular chaperones, translational attenuation, ER-associated degradation, and other mechanisms. Under prolonged and irremediable ER stress, however, the UPR can also trigger apoptosis. Here, we report that in cells infected with the avian coronavirus infectious bronchitis virus (IBV), ER stress was induced and the IRE1α-XBP1 pathway of UPR was activated. Knockdown and overexpression experiments demonstrated that IRE1α protects infected cells from IBV-induced apoptosis, which required both its kinase and RNase activities. Our data also suggest that splicing of XBP1 mRNA by IRE1α appears to convert XBP1 from a proapoptotic XBP1u protein to a prosurvival XBP1s protein. Moreover, IRE1α antagonized IBV-induced apoptosis by modulating the phosphorylation status of the proapoptotic c-Jun N-terminal kinase (JNK) and the prosurvival RAC–alpha serine/threonine-protein kinase (Akt). Taken together, the data indicate that the ER stress sensor IRE1α is activated in IBV-infected cells and serves as a survival factor during coronavirus infection. IMPORTANCE Animal coronaviruses are important veterinary viruses, which could cross the species barrier, becoming severe human pathogens. Molecular characterization of the interactions between coronaviruses and host cells is pivotal to understanding the pathogenicity and species specificity of coronavirus infection. It has been well established that the endoplasmic reticulum (ER) is closely associated with coronavirus replication. Here, we report that inositol-requiring protein 1 alpha (IRE1α), a key sensor of ER stress, is activated in cells infected with the avian coronavirus infectious bronchitis virus (IBV). Moreover, IRE1α is shown to protect the infected cells from apoptosis by modulating the unfolded-protein response (UPR) and two kinases related to cell survival. This study demonstrates that UPR activation constitutes a major aspect of coronavirus-host interactions. Manipulations of the coronavirus-induced UPR may provide novel therapeutic targets for the control of coronavirus infection and pathogenesis.",,"['Fung, To Sing', 'Liao, Ying', 'Liu, Ding Xiang']",,,,
,PMC,Intrabronchial Infection of Rhesus Macaques with Simian Varicella Virus Results in a Robust Immune Response in the Lungs,http://dx.doi.org/10.1128/JVI.01814-14,PMC4248928,,,"Varicella-zoster virus (VZV) is the etiological agent of varicella (chickenpox) and herpes zoster (shingles). Primary VZV infection is believed to occur via the inhalation of virus either in respiratory droplets or from shedding varicella lesions or by direct contact with infectious vesicular fluid. However, the ensuing immune response in the lungs remains incompletely understood. We have shown that intrabronchial inoculation of rhesus macaques with simian varicella virus (SVV), a homolog of VZV, recapitulates the hallmarks of acute and latent VZV infection in humans. In this study, we performed an in-depth analysis of the host immune response to acute SVV infection in the lungs and peripheral blood. We report that acute SVV infection results in a robust innate immune response in the lungs, characterized by the production of inflammatory cytokines, chemokines, and growth factors as well as an increased frequency of plasmacytoid dendritic cells (DCs) that corresponded with alpha interferon (IFN-α) production and a rapid decrease in viral loads in the lungs. This is followed by T and B cell proliferation, antibody production, T cell differentiation, and cytokine production, which correlate with the complete cessation of viral replication. Although terminally differentiated CD8 T cells became the predominant T cell population in bronchoalveolar lavage cells, a higher percentage of CD4 T cells were SVV specific, which suggests a critical role for these cells in the resolution of primary SVV infection in the lungs. Given the homology between SVV and VZV, our data provide insight into the immune response to VZV within the lung. IMPORTANCE Although primary VZV infection occurs primarily via the respiratory route, the host response in the lungs and its contribution to the cessation of viral replication and establishment of latency remain poorly understood. The difficulty in accessing lung tissue and washes from individuals infected with VZV has hampered efforts to address this knowledge gap. SVV infection of rhesus macaques is an important model of VZV infection of humans; therefore, we utilized this animal model to gain a comprehensive view of the kinetics of the immune response to SVV in the lung and its relationship to the resolution of acute infection in respiratory tissues. These data not only advance our understanding of host immunity to VZV, a critical step in developing new vaccines, but also provide additional insight into immunity to respiratory pathogens.",,"['Haberthur, Kristen', 'Meyer, Christine', 'Arnold, Nicole', 'Engelmann, Flora', 'Jeske, Daniel R.', 'Messaoudi, Ilhem']",,,,
,PMC,Investigating a Mystery Disease: Tales from a Viral Detective,http://dx.doi.org/10.1128/JVI.00708-14,PMC4248903,,,"Viral outbreak investigation is challenging logistically as well as scientifically. In the context of addressing a fictional emerging viral disease, I describe the process of discovery, from the initial report of a problem through discussions of intellectual property and sample management, study design, management, experimental execution, and reporting of results.",,"Lipkin, W. Ian",,,,
,PMC,Methyltransferase-Defective Avian Metapneumovirus Vaccines Provide Complete Protection against Challenge with the Homologous Colorado Strain and the Heterologous Minnesota Strain,http://dx.doi.org/10.1128/JVI.01095-14,PMC4248898,,,"Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey rhinotracheitis virus, is the causative agent of turkey rhinotracheitis and is associated with swollen head syndrome in chickens. Since its discovery in the 1970s, aMPV has been recognized as an economically important pathogen in the poultry industry worldwide. The conserved region VI (CR VI) of the large (L) polymerase proteins of paramyxoviruses catalyzes methyltransferase (MTase) activities that typically methylate viral mRNAs at guanine N-7 (G-N-7) and ribose 2′-O positions. In this study, we generated a panel of recombinant aMPV (raMPV) Colorado strains carrying mutations in the S-adenosyl methionine (SAM) binding site in the CR VI of L protein. These recombinant viruses were specifically defective in ribose 2′-O, but not G-N-7 methylation and were genetically stable and highly attenuated in cell culture and viral replication in the upper and lower respiratory tracts of specific-pathogen-free (SPF) young turkeys. Importantly, turkeys vaccinated with these MTase-defective raMPVs triggered a high level of neutralizing antibody and were completely protected from challenge with homologous aMPV Colorado strain and heterologous aMPV Minnesota strain. Collectively, our results indicate (i) that aMPV lacking 2′-O methylation is highly attenuated in vitro and in vivo and (ii) that inhibition of mRNA cap MTase can serve as a novel target to rationally design live attenuated vaccines for aMPV and perhaps other paramyxoviruses. IMPORTANCE Paramyxoviruses include many economically and agriculturally important viruses such as avian metapneumovirus (aMPV), and Newcastle disease virus (NDV), human pathogens such as human respiratory syncytial virus, human metapneumovirus, human parainfluenza virus type 3, and measles virus, and highly lethal emerging pathogens such as Nipah virus and Hendra virus. For many of them, there is no effective vaccine or antiviral drug. These viruses share common strategies for viral gene expression and replication. During transcription, paramyxoviruses produce capped, methylated, and polyadenylated mRNAs. Using aMPV as a model, we found that viral ribose 2′-O methyltransferase (MTase) is a novel approach to rationally attenuate the virus for vaccine purpose. Recombinant aMPV (raMPV) lacking 2′-O MTase were not only highly attenuated in turkeys but also provided complete protection against the challenge of homologous and heterologous aMPV strains. This novel approach can be applicable to other animal and human paramyxoviruses for rationally designing live attenuated vaccines.",,"['Sun, Jing', 'Wei, Yongwei', 'Rauf, Abdul', 'Zhang, Yu', 'Ma, Yuanmei', 'Zhang, Xiaodong', 'Shilo, Konstantin', 'Yu, Qingzhong', 'Saif, Y. M.', 'Lu, Xingmeng', 'Yu, Lian', 'Li, Jianrong']",,,,
,PMC,Influenza A Virus Polymerase Is a Site for Adaptive Changes during Experimental Evolution in Bat Cells,http://dx.doi.org/10.1128/JVI.01857-14,PMC4248895,,,"The recent identification of highly divergent influenza A viruses in bats revealed a new, geographically dispersed viral reservoir. To investigate the molecular mechanisms of host-restricted viral tropism and the potential for transmission of viruses between humans and bats, we exposed a panel of cell lines from bats of diverse species to a prototypical human-origin influenza A virus. All of the tested bat cell lines were susceptible to influenza A virus infection. Experimental evolution of human and avian-like viruses in bat cells resulted in efficient replication and created highly cytopathic variants. Deep sequencing of adapted human influenza A virus revealed a mutation in the PA polymerase subunit not previously described, M285K. Recombinant virus with the PA M285K mutation completely phenocopied the adapted virus. Adaptation of an avian virus-like virus resulted in the canonical PB2 E627K mutation that is required for efficient replication in other mammals. None of the adaptive mutations occurred in the gene for viral hemagglutinin, a gene that frequently acquires changes to recognize host-specific variations in sialic acid receptors. We showed that human influenza A virus uses canonical sialic acid receptors to infect bat cells, even though bat influenza A viruses do not appear to use these receptors for virus entry. Our results demonstrate that bats are unique hosts that select for both a novel mutation and a well-known adaptive mutation in the viral polymerase to support replication. IMPORTANCE Bats constitute well-known reservoirs for viruses that may be transferred into human populations, sometimes with fatal consequences. Influenza A viruses have recently been identified in bats, dramatically expanding the known host range of this virus. Here we investigated the replication of human influenza A virus in bat cell lines and the barriers that the virus faces in this new host. Human influenza A and B viruses infected cells from geographically and evolutionarily diverse New and Old World bats. Viruses mutated during infections in bat cells, resulting in increased replication and cytopathic effects. These mutations were mapped to the viral polymerase and shown to be solely responsible for adaptation to bat cells. Our data suggest that replication of human influenza A viruses in a nonnative host drives the evolution of new variants and may be an important source of genetic diversity.",,"['Poole, Daniel S.', 'Yú, Shuǐqìng', 'Caì, Yíngyún', 'Dinis, Jorge M.', 'Müller, Marcel A.', 'Jordan, Ingo', 'Friedrich, Thomas C.', 'Kuhn, Jens H.', 'Mehle, Andrew']",,,,
,PMC,Catalytic Function and Substrate Specificity of the Papain-Like Protease Domain of nsp3 from the Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.01294-14,PMC4248884,,,"The papain-like protease (PLpro) domain from the deadly Middle East respiratory syndrome coronavirus (MERS-CoV) was overexpressed and purified. MERS-CoV PLpro constructs with and without the putative ubiquitin-like (UBL) domain at the N terminus were found to possess protease, deubiquitinating, deISGylating, and interferon antagonism activities in transfected HEK293T cells. The quaternary structure and substrate preferences of MERS-CoV PLpro were determined and compared to those of severe acute respiratory syndrome coronavirus (SARS-CoV) PLpro, revealing prominent differences between these closely related enzymes. Steady-state kinetic analyses of purified MERS-CoV and SARS-CoV PLpros uncovered significant differences in their rates of hydrolysis of 5-aminomethyl coumarin (AMC) from C-terminally labeled peptide, ubiquitin, and ISG15 substrates, as well as in their rates of isopeptide bond cleavage of K48- and K63-linked polyubiquitin chains. MERS-CoV PLpro was found to have 8-fold and 3,500-fold higher catalytic efficiencies for hydrolysis of ISG15-AMC than for hydrolysis of the Ub-AMC and Z-RLRGG-AMC substrates, respectively. A similar trend was observed for SARS-CoV PLpro, although it was much more efficient than MERS-CoV PLpro toward ISG15-AMC and peptide-AMC substrates. MERS-CoV PLpro was found to process K48- and K63-linked polyubiquitin chains at similar rates and with similar debranching patterns, producing monoubiquitin species. However, SARS-CoV PLpro much preferred K48-linked polyubiquitin chains to K63-linked chains, and it rapidly produced di-ubiquitin molecules from K48-linked chains. Finally, potent inhibitors of SARS-CoV PLpro were found to have no effect on MERS-CoV PLpro. A homology model of the MERS-CoV PLpro structure was generated and compared to the X-ray structure of SARS-CoV PLpro to provide plausible explanations for differences in substrate and inhibitor recognition. IMPORTANCE Unlocking the secrets of how coronavirus (CoV) papain-like proteases (PLpros) perform their multifunctional roles during viral replication entails a complete mechanistic understanding of their substrate recognition and enzymatic activities. We show that the PLpro domains from the MERS and SARS coronaviruses can recognize and process the same substrates, but with different catalytic efficiencies. The differences in substrate recognition between these closely related PLpros suggest that neither enzyme can be used as a generalized model to explain the kinetic behavior of all CoV PLpros. As a consequence, decoding the mechanisms of PLpro-mediated antagonism of the host innate immune response and the development of anti-CoV PLpro enzyme inhibitors will be a challenging undertaking. The results from this study provide valuable information for understanding how MERS-CoV PLpro-mediated antagonism of the host innate immune response is orchestrated, as well as insight into the design of inhibitors against MERS-CoV PLpro.",,"['Báez-Santos, Yahira M.', 'Mielech, Anna M.', 'Deng, Xufang', 'Baker, Susan', 'Mesecar, Andrew D.']",,,,
,PMC,Mining the human autoantibody repertoire: Isolation of potent IL17A-neutralizing monoclonal antibodies from a patient with thymoma,http://dx.doi.org/10.4161/mabs.36292,PMC4623001,,,"Anti-cytokine autoantibodies have been widely reported to be present in human plasma, both in healthy subjects and in patients with underlying autoimmune conditions, such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) or thymic epithelial neoplasms. While often asymptomatic, they can cause or facilitate a wide range of diseases including opportunistic infections. The potential therapeutic value of specific neutralizing anti-cytokine autoantibodies has not been thoroughly investigated. Here we used mammalian cell display to isolate IL17A-specific antibodies from a thymoma patient with proven high-titer autoantibodies against the same. We identified 3 distinct clonotypes that efficiently neutralized IL17A in a cell-based in vitro assay. Their potencies were comparable to those of known neutralizing antibodies, including 2, AIN457 (secukinumab) and ixekizumab that are currently in clinical development for the treatment of various inflammatory disorders. These data clearly demonstrate that the human autoantibody repertoire can be mined for antibodies with high therapeutic potential for clinical development.",,"['Beerli, Roger R', 'Bauer, Monika', 'Fritzer, Andrea', 'Rosen, Lindsey B', 'Buser, Regula B', 'Hanner, Markus', 'Maudrich, Melanie', 'Nebenfuehr, Mario', 'Toepfer, Jorge Alejandro Sepulveda', 'Mangold, Susanne', 'Bauer, Anton', 'Holland, Steven M', 'Browne, Sarah K', 'Meinke, Andreas']",,,,
,PMC,Responding to the Potential of Ebola Virus Disease (EVD) Importation into Malaysia,,PMC4391448,,,"The current Ebola outbreak, which is the first to affect West African countries, has been declared to have met the conditions for a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO). Thus, the Ministry of Health (MOH) of Malaysia has taken steps to strengthen and enhanced the five core components of preparedness and response to mitigate the outbreak. The National Crisis Preparedness and Response Centre (CPRC) commands, controls and coordinates the preparedness and response plans for disasters, outbreaks, crises and emergencies (DOCE) related to health in a centralised way. Through standardised case definition and mandatory notification of Ebola by public and private practitioners, surveillance of Ebola is made possible. Government hospitals and laboratories have been identified to manage and diagnose Ebola virus infections, and medical staff members have been trained to handle an Ebola outbreak, with emphasis on strict infection prevention and control practices. Monitoring of the points of entry, focusing on travellers and students visiting or coming from West African countries is made possible by interagency collaborations. To alleviate the public’s anxiety, effective risk communications are being delivered through various channels. With experience in past outbreak control, the MOH’s preparedness and response plans are in place to abate an Ebola outbreak.",,"['WAN MOHAMED NOOR, Wan Noraini', 'SANDHU, Sukhvinder Singh', 'AHMAD MAHIR, Husna Maizura', 'KURUP, Devan', 'RUSLI, Norhayati', 'SAAT, Zainah', 'CHONG, Chee Kheong', 'SULAIMAN, Lokman Hakim', 'ABDULLAH, Noor Hisham']",,,,
,PMC,Sculpting the proteome with small molecules,http://dx.doi.org/10.1038/nchembio.1671,PMC4639395,,,"The ubiquitin-proteasome system (UPS) pervades the biology of eukaryotes. Because it depends on the activity of hundreds of different enzymes and protein-protein interactions, the UPS provides many opportunities for selective modulation of the pathway with small molecules. Here we discuss the principles that underlie the development of effective inhibitors or activators of the pathway. We emphasize insights from structural analysis and describe strategies for evaluating the selectivity of compounds.",,"['King, Randall W.', 'Finley, Daniel']",,,,
,PMC,Interleukin 10 modulation of pathogenic Th17 cells during fatal alphavirus encephalomyelitis,http://dx.doi.org/10.1073/pnas.1418966111,PMC4234572,,,"Mosquito-borne alphaviruses are important causes of epidemic encephalomyelitis. Neuronal cell death during fatal alphavirus encephalomyelitis is immune-mediated; however, the types of cells involved and their regulation have not been determined. We show that the virus-induced inflammatory response was accompanied by production of the regulatory cytokine IL-10, and in the absence of IL-10, paralytic disease occurred earlier and mice died faster. To determine the reason for accelerated disease in the absence of IL-10, immune responses in the CNS of IL-10(−/−) and wild-type (WT) mice were compared. There were no differences in the amounts of brain inflammation or peak virus replication; however, IL-10(−/−) animals had accelerated and increased infiltration of CD4(+)IL-17A(+) and CD4(+)IL-17A(+)IFNγ(+) cells compared with WT animals. Th17 cells infiltrating the brain demonstrated a pathogenic phenotype with the expression of the transcription factor, Tbet, and the production of granzyme B, IL-22, and GM-CSF, with greater production of GM-CSF in IL-10(−/−) mice. Therefore, in fatal alphavirus encephalomyelitis, pathogenic Th17 cells enter the CNS at the onset of neurologic disease and, in the absence of IL-10, appear earlier, develop into Th1/Th17 cells more often, and have greater production of GM-CSF. This study demonstrates a role for pathogenic Th17 cells in fatal viral encephalitis.",,"['Kulcsar, Kirsten A.', 'Baxter, Victoria K.', 'Greene, Ivorlyne P.', 'Griffin, Diane E.']",,,,
,PMC,Tackling feline infectious peritonitis via reverse genetics,http://dx.doi.org/10.4161/bioe.32133,PMC4601228,,,"Feline infectious peritonitis (FIP) is caused by feline coronaviruses (FCoVs) and represents one of the most important lethal infectious diseases of cats. To date, there is no efficacious prevention and treatment, and our limited knowledge on FIP pathogenesis is mainly based on analysis of experiments with field isolates. In a recent study, we reported a promising approach to study FIP pathogenesis using reverse genetics. We generated a set of recombinant FCoVs and investigated their pathogenicity in vivo. The set included the type I FCoV strain Black, a type I FCoV strain Black with restored accessory gene 7b, two chimeric type I/type II FCoVs and the highly pathogenic type II FCoV strain 79–1146. All recombinant FCoVs and the reference strain isolates were found to establish productive infections in cats. While none of the type I FCoVs and chimeric FCoVs induced FIP, the recombinant type II FCoV strain 79–1146 was as pathogenic as the parental isolate. Interestingly, an intact ORF 3c was confirmed to be restored in all viruses (re)isolated from FIP-diseased animals.",,"['Thiel, Volker', 'Thiel, Heinz-Jürgen', 'Tekes, Gergely']",,,,
,PMC,Site-specific antibody-drug conjugation through an engineered glycotransferase and a chemically reactive sugar,http://dx.doi.org/10.4161/mabs.29889,PMC4622437,,,"Conjugation of small molecule drugs to specific sites on the antibody molecule has been increasingly used for the generation of relatively homogenous preparations of antibody-drug conjugates (ADCs) with physicochemical properties similar or identical to those of the naked antibody. Previously a method for conjugation of small molecules to glycoproteins through existing glycans by using an engineered glycotransferase and a chemically reactive sugar as a handle was developed. Here, for the first time, we report the use of this method with some modifications to generate an ADC from a monoclonal antibody, m860, which we identified from a human naïve phage display Fab library by panning against the extracellular domain of human HER2. M860 bound to cell surface-associated HER2 with affinity comparable to that of Trastuzumab (Herceptin®), but to a different epitope. The m860ADC was generated by enzymatically adding a reactive keto-galactose to m860 using an engineered glycotransferase and conjugating the reactive m860 to aminooxy auristatin F. It exhibited potent and specific cell-killing activity against HER2 positive cancer cells, including trastuzumab-resistant breast cancer cells. This unique ADC may have utility as a potential therapeutic for HER2 positive cancers alone or in combination with other drugs. Our results also validate the keto-galactose/engineered glycotransferase method for generation of functional ADCs, which could potentially also be used for preparation of ADCs targeting other disease markers.",,"['Zhu, Zhongyu', 'Ramakrishnan, Boopathy', 'Li, Jinyu', 'Wang, Yanping', 'Feng, Yang', 'Prabakaran, Ponraj', 'Colantonio, Simona', 'Dyba, Marzena A', 'Qasba, Pradman K', 'Dimitrov, Dimiter S']",,,,
,PMC,Internet and Free Press Are Associated with Reduced Lags in Global Outbreak Reporting,http://dx.doi.org/10.1371/currents.outbreaks.cecdec16fa17091eea4c4a725dba9e16,PMC4234456,25642380,CC BY,"Background: Global outbreak detection and reporting have generally improved for a variety of infectious diseases and geographic regions in recent decades. Nevertheless, lags in outbreak reporting remain a threat to the global human health and economy. In the time between first occurrence of a novel disease incident and public notification of an outbreak, infected individuals have a greater possibility of traveling and spreading the pathogen to other nations. Shortening outbreak reporting lags has the potential to improve global health by preventing local outbreaks from escalating into global epidemics. Methods: Reporting lags between the first record and the first public report of an event were calculated for 318 outbreaks occurring 1996-2009. The influence of freedom of the press, Internet usage, per capita health expenditure, and cell phone subscriptions, on the timeliness of outbreak reporting was evaluated. Results: Freer presses and increasing Internet usage correlate with reduced time between the first record of an outbreak and the public report. Increasing Internet usage reduced the expected reporting lag from more than one month in nations without Internet users to one day in those where 75 of 100 people use the Internet. Conclusion: Advances in technology and the emergence of more open and free governments are associated with to improved global infectious disease surveillance.",2014 Oct 30,"['McAlarnen, Lindsey', 'Smith, Katherine', 'Brownstein, John S.', 'Jerde, Christopher']",PLoS Curr,,,
,PMC,A Unified Mechanism for Aminopeptidase N-based Tumor Cell Motility and Tumor-homing Therapy,http://dx.doi.org/10.1074/jbc.M114.566802,PMC4263860,,,"Tumor cell surface aminopeptidase N (APN or CD13) has two puzzling functions unrelated to its enzymatic activity: mediating tumor cell motility and serving as a receptor for tumor-homing peptides (peptides that bring anti-cancer drugs to tumor cells). To investigate APN-based tumor-homing therapy, we determined the crystal structure of APN complexed with a tumor-homing peptide containing a representative Asn-Gly-Arg (NGR) motif. The tumor-homing peptide binds to the APN enzymatic active site, but it resists APN degradation due to a distorted scissile peptide bond. To explore APN-based tumor cell motility, we examined the interactions between APN and extracellular matrix (ECM) proteins. APN binds to, but does not degrade, NGR motifs in ECM proteins that share similar conformations with the NGR motif in the APN-bound tumor-homing peptide. Therefore, APN-based tumor cell motility and tumor-homing therapy rely on a unified mechanism in which both functions are driven by the specific and stable interactions between APN and the NGR motifs in ECM proteins and tumor-homing peptides. This study further implicates APN as an integrin-like molecule that functions broadly in cell motility and adhesion by interacting with its signature NGR motifs in the extracellular environment.",,"['Liu, Chang', 'Yang, Yang', 'Chen, Lang', 'Lin, Yi-Lun', 'Li, Fang']",,,,
,PMC,Interactome Analysis of the Human Respiratory Syncytial Virus RNA Polymerase Complex Identifies Protein Chaperones as Important Cofactors That Promote L-Protein Stability and RNA Synthesis,http://dx.doi.org/10.1128/JVI.01783-14,PMC4300676,,,"The human respiratory syncytial virus (HRSV) core viral RNA polymerase comprises the large polymerase protein (L) and its cofactor, the phosphoprotein (P), which associate with the viral ribonucleoprotein complex to replicate the genome and, together with the M2-1 protein, transcribe viral mRNAs. While cellular proteins have long been proposed to be involved in the synthesis of HRSV RNA by associating with the polymerase complex, their characterization has been hindered by the difficulty of purifying the viral polymerase from mammalian cell culture. In this study, enhanced green fluorescent protein (EGFP)-tagged L- and P-protein expression was coupled with high-affinity anti-GFP antibody-based immunoprecipitation and quantitative proteomics to identify cellular proteins that interacted with either the L- or the P-proteins when expressed as part of a biologically active viral RNP. Several core groups of cellular proteins were identified that interacted with each viral protein including, in both cases, protein chaperones. Ablation of chaperone activity by using small-molecule inhibitors confirmed previously reported studies which suggested that this class of proteins acted as positive viral factors. Inhibition of HSP90 chaperone function in the current study showed that HSP90 is critical for L-protein function and stability, whether in the presence or absence of the P-protein. Inhibition studies suggested that HSP70 also disrupts virus biology and might help the polymerase remodel the nucleocapsid to allow RNA synthesis to occur efficiently. This indicated a proviral role for protein chaperones in HRSV replication and demonstrates that the function of cellular proteins can be targeted as potential therapeutics to disrupt virus replication. IMPORTANCE Human respiratory syncytial virus (HRSV) represents a major health care and economic burden, being the main cause of severe respiratory infections in infants worldwide. No vaccine or effective therapy is available. This study focused on identifying those cellular proteins that potentially interact specifically with the viral proteins that are central to virus replication and transcription, with a view to providing potential targets for the development of a specific, transient therapeutic which disrupts virus biology but prevents the emergence of resistance, while maintaining cell viability. In particular, protein chaperones (heat shock proteins 70 and 90), which aid protein folding and function, were identified. The mechanism by which these chaperones contribute to virus biology was tested, and this study demonstrates to the field that cellular protein chaperones may be required for maintaining the correct folding and therefore functionality of specific proteins within the virus replication complex.",,"['Munday, Diane C.', 'Wu, Weining', 'Smith, Nikki', 'Fix, Jenna', 'Noton, Sarah Louise', 'Galloux, Marie', 'Touzelet, Olivier', 'Armstrong, Stuart D.', 'Dawson, Jenna M.', 'Aljabr, Waleed', 'Easton, Andrew J.', 'Rameix-Welti, Marie-Anne', 'de Oliveira, Andressa Peres', 'Simabuco, Fernando M.', 'Ventura, Armando M.', 'Hughes, David J.', 'Barr, John N.', 'Fearns, Rachel', 'Digard, Paul', 'Eléouët, Jean-François', 'Hiscox, Julian A.']",,,,
,PMC,Cocirculation of Two Distinct Genetic and Antigenic Lineages of Proposed Influenza D Virus in Cattle,http://dx.doi.org/10.1128/JVI.02718-14,PMC4300623,,,"Viruses with approximately 50% homology to human influenza C virus (ICV) have recently been isolated from swine and cattle. The overall low homology to ICV, lack of antibody cross-reactivity to ICV in hemagglutination inhibition (HI) and agar gel immunodiffusion assays, and inability to productively reassort with ICV led to the proposal that these viruses represented a new genus of influenza virus, influenzavirus D (IDV). To further our understanding of the epidemiology of IDV, real-time reverse transcription-PCR was performed on a set of 208 samples from bovines with respiratory disease. Ten samples (4.8%) were positive and six viruses were successfully isolated in vitro. Phylogenetic analysis of full-genome sequences of these six new viruses and four previously reported viruses revealed two distinct cocirculating lineages represented by D/swine/Oklahoma/1334/2011 (D/OK) and D/bovine/Oklahoma/660/2013 (D/660), which frequently reassorted with one another. Antigenic analysis using the HI assay and lineage-representative D/OK and D/660 antiserum found up to an approximate 10-fold loss in cross-reactivity against heterologous clade antiserum. One isolate, D/bovine/Texas/3-13/2011 (D/3-13), clustered with the D/660 lineage, but also had high HI titers to heterologous (D/OK) clade antiserum. Molecular modeling of the hemagglutinin esterase fusion protein of D/3-13 identified a mutation at position 212 as a possible antigenic determinant responsible for the discrepant HI results. These results suggest that IDV is common in bovines with respiratory disease and that at least two genetic and antigenically distinct clades cocirculate. IMPORTANCE A novel bovine influenza virus was recently identified. Detailed genetic and antigenic studies led to the proposal that this virus represents a new genus of influenza, influenzavirus D (IDV). Here, we show that IDV is common in clinical samples of bovine respiratory disease complex (BRDC), with a prevalence similar to that of other established BRDC etiological agents. These results are in good agreement with the near-ubiquitous seroprevalence of IDV previously found. Phylogenetic analysis of complete genome sequences found evidence for two distinct cocirculating lineages of IDV which freely reassort. Significant antigenic differences, which generally agreed with the surface glycoprotein hemagglutinin esterase phylogeny, were observed between the two lineages. Based on these results, and on the ability of IDV to infect and transmit in multiple mammalian species, additional studies to determine the pathogenic potential of IDV are warranted.",,"['Collin, Emily A.', 'Sheng, Zizhang', 'Lang, Yuekun', 'Ma, Wenjun', 'Hause, Ben M.', 'Li, Feng']",,,,
,PMC,CEACAM1 regulates TIM–3–mediated tolerance and exhaustion,http://dx.doi.org/10.1038/nature13848,PMC4297519,,,"T-cell immunoglobulin domain and mucin domain-3 (TIM-3, also known as HAVCR2) is an activation-induced inhibitory molecule involved in tolerance and shown to induce T-cell exhaustion in chronic viral infection and cancers(1–5). Under some conditions, TIM-3 expression has also been shown to be stimulatory. Considering that TIM-3, like cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death 1 (PD-1), is being targeted for cancer immunotherapy, it is important to identify the circumstances under which TIM-3 can inhibit and activate T-cell responses. Here we show that TIM-3 is co-expressed and forms a heterodimer with carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), another well-known molecule expressed on activated T cells and involved in T-cell inhibition(6–10). Biochemical, biophysical and X-ray crystallography studies show that the membrane-distal immunoglobulin-variable (IgV)-like amino-terminal domain of each is crucial to these interactions. The presence of CEACAM1 endows TIM-3 with inhibitory function. CEACAM1 facilitates the maturation and cell surface expression of TIM-3 by forming a heterodimeric interaction in cis through the highly related membrane-distal N-terminal domains of each molecule. CEACAM1 and TIM-3 also bind in trans through their N-terminal domains. Both cis and trans interactions between CEACAM1 and TIM-3 determine the tolerance-inducing function of TIM-3. In a mouse adoptive transfer colitis model, CEACAM1-deficient T cells are hyper-inflammatory with reduced cell surface expression of TIM-3 and regulatory cytokines, and this is restored by T-cell-specific CEACAM1 expression. During chronic viral infection and in a tumour environment, CEACAM1 and TIM-3 mark exhausted T cells. Co-blockade of CEACAM1 and TIM-3 leads to enhancement of anti-tumour immune responses with improved elimination of tumours in mouse colorectal cancer models. Thus, CEACAM1 serves as a heterophilic ligand for TIM-3 that is required for its ability to mediate T-cell inhibition, and this interaction has a crucial role in regulating autoimmunity and anti-tumour immunity.",,"['Huang, Yu-Hwa', 'Zhu, Chen', 'Kondo, Yasuyuki', 'Anderson, Ana C.', 'Gandhi, Amit', 'Russell, Andrew', 'Dougan, Stephanie K.', 'Petersen, Britt-Sabina', 'Melum, Espen', 'Pertel, Thomas', 'Clayton, Kiera L.', 'Raab, Monika', 'Chen, Qiang', 'Beauchemin, Nicole', 'Yazaki, Paul J.', 'Pyzik, Michal', 'Ostrowski, Mario A.', 'Glickman, Jonathan N.', 'Rudd, Christopher E.', 'Ploegh, Hidde L.', 'Franke, Andre', 'Petsko, Gregory A.', 'Kuchroo, Vijay K.', 'Blumberg, Richard S.']",,,,
,PMC,Assessing the impact of travel restrictions on international spread of the 2014 West African Ebola epidemic,,PMC4415609,,,"The quick spread of an Ebola outbreak in West Africa has led a number of countries and airline companies to issue travel bans to the affected areas. Considering data up to 31 Aug 2014, we assess the impact of the resulting traffic reductions with detailed numerical simulations of the international spread of the epidemic. Traffic reductions are shown to delay by only a few weeks the risk that the outbreak extends to new countries.",,"['Poletto, Chiara', 'Gomes, Marcelo F. C.', 'Piontti, Ana Pastore y', 'Rossi, Luca', 'Bioglio, Livio', 'Chao, Dennis L.', 'Longini, Ira M.', 'Halloran, M. Elizabeth', 'Colizza, Vittoria', 'Vespignani, Alessandro']",,,,
,PMC,Injury-induced MRP8/MRP14 stimulates IP-10/CXCL10 in monocytes/macrophages,http://dx.doi.org/10.1096/fj.14-255992,PMC4285539,,,"Trauma/hemorrhagic shock is associated with morbidity and mortality due to dysregulated inflammation, which is driven in part by monocytes/macrophages stimulated by injury-induced release of damage-associated molecular pattern (DAMP) molecules. MRP8/MRP14 is an endogenous DAMP involved in various inflammatory diseases, though its mechanism of action is unclear. Circulating MRP8/MRP14 levels in human blunt trauma nonsurvivors were significantly lower than those of survivors (P < 0.001). Human monocytic THP-1 cells stimulated with MRP8/MRP14 expressed the chemokine IFN-γ inducible protein 10 (IP-10)/CXCL10. Circulating IP-10 levels in human blunt trauma patients were correlated positively with MRP8/MRP14 levels (r = 0.396, P < 0.001), and were significantly lower in trauma nonsurvivors than in survivors (P < 0.001). We therefore sought to determine the mechanisms by which MRP8/MRP14 stimulates IP-10 in monocytes/macrophages, and found that induction of IP-10 by MRP8/MRP14 required Toll-like receptor 4 and TRIF but not MyD88. Full induction of IP-10 by MRP8/MRP14 required synergy between the transcription factors NF-κB and IFN regulatory factor 3 (IRF3). The receptor for IP-10 is CXCR3, and MRP8/MRP14-induced chemotaxis of CXCR3(+) cells was dependent on the production of IP-10 in monocytes/macrophages. Furthermore, in vivo study with a mouse trauma/hemorrhagic shock model showed that administration of neutralizing antibody against MRP8 prevented activation of NF-κB and IRF3 as well as IP-10 production. Thus, the current study identified a novel signaling mechanism that controls IP-10 expression in monocytes/macrophages by MRP8/MRP14, which may play an important role in injury-induced inflammation.—Wang, J., Vodovotz, Y., Fan, L., Li, Y., Liu, Z., Namas, R., Barclay, D., Zamora, R., Billiar, T. R., Wilson, M. A., Fan, J., Jiang, Y. Injury-induced MRP8/MRP14 stimulates IP-10/CXCL10 in monocytes/macrophages.",,"['Wang, Juan', 'Vodovotz, Yoram', 'Fan, Liyan', 'Li, Yuehua', 'Liu, Zheng', 'Namas, Rami', 'Barclay, Derek', 'Zamora, Ruben', 'Billiar, Timothy R.', 'Wilson, Mark A.', 'Fan, Jie', 'Jiang, Yong']",,,,
,PMC,Distinct Patterns of B-Cell Activation and Priming by Natural Influenza Virus Infection Versus Inactivated Influenza Vaccination,http://dx.doi.org/10.1093/infdis/jiu580,PMC4366605,,,"Background. The human B-cell response to natural influenza virus infection has not been extensively investigated at the polyclonal level. Methods. The overall B-cell response of patients acutely infected with the 2009 pandemic influenza A(H1N1)pdm09 virus (A[H1N1]pdm09) was analyzed by determining the reactivity of plasmablast-derived polyclonal antibodies (PPAbs) to influenza proteins. Recipients of inactivated influenza vaccine containing the same A(H1N1)pdm09 strain were studied for comparison. Results. During acute infection, robust plasmablast responses to the infecting virus were detected, characterized by a greater PPAb reactivity to the conserved influenza virus nuclear protein and to heterovariant and heterosubtypic hemagglutinins, in comparison to responses to the inactivated A(H1N1)pdm09 vaccine. In A(H1N1)pdm09 vaccinees, the presence of baseline serum neutralizing antibodies against A(H1N1)pdm09, suggesting previous exposure to natural A(H1N1)pdm09 infection, did not affect the plasmablast response to vaccination, whereas repeated immunization with inactivated A(H1N1)pdm09 vaccine resulted in significantly reduced vaccine-specific and cross-reactive PPAb responses. Conclusions. Natural A(H1N1)pdm09 infection and inactivated A(H1N1)pdm09 vaccination result in very distinct patterns of B-cell activation and priming. These differences are likely to be associated with differences in protective immunity, especially cross-protection against heterovariant and heterosubtypic influenza virus strains.",,"['He, Xiao-Song', 'Holmes, Tyson H.', 'Sanyal, Mrinmoy', 'Albrecht, Randy A.', 'García-Sastre, Adolfo', 'Dekker, Cornelia L.', 'Davis, Mark M.', 'Greenberg, Harry B.']",,,,
,PMC,MERS-CoV– Low risk to Canadians,http://dx.doi.org/10.14745/ccdr.v40i17a01,PMC5864465,,,"Middle East respiratory syndrome – Coronavirus (MERS-CoV) -- is a novel coronavirus that has caused a number of community-acquired cases and health care associated outbreaks in Saudi Arabia and the United Arab Emirates (UAE) as well as sporadic cases in other countries, especially in the Middle East. The evidence to date links MERS-CoV cases with exposure to camels, including camel products or to probable or confirmed human cases of MERS-CoV. It typically presents as an acute respiratory illness and is associated with a 35% mortality rate. Based on available information at this time, the current risk to Canadians for acquiring MERS-CoV infections is considered low. However, the International Health Regulations Committee concerning MERS-CoV has cautioned that the upsurge of cases seen this past spring (2014) may be predictive of an increase in cases related to the Hajj – an annual pilgrimage to Mecca in Saudi Arabia that took place in early October 2014. Although the overall risk is low, the Public Health Agency of Canada and its National Microbiology Laboratory (NML) in close collaboration with provincial and territorial partners, the Canadian Public Health Laboratory Network (CPHLN) and infection prevention and control experts have developed a number of preparedness guidance documents and protocols to address the risk of an imported case of MERS-CoV in Canada.",,"['Saboui, M', 'Reyes-Domingo, F', 'Levreault, E', 'Mersereau, T']",,,,
,PMC,Camouflage and Misdirection: The Full-On Assault of Ebola Virus Disease,http://dx.doi.org/10.1016/j.cell.2014.10.006,PMC4243531,,,"Ebolaviruses cause a severe hemorrhagic fever syndrome that is rapidly fatal to humans and non-human primates. Ebola protein interactions with host cellular proteins disrupt Type I and Type II interferon responses, RNAi anti-viral responses, antigen presentation, T-cell mediated antibody responses, humoral antibodies and cell mediated immunity. This multifaceted approach to evasion and suppression of innate and adaptive immune responses in their target hosts leads to the severe immune dysregulation and “cytokine storm” that is characteristic of fatal ebolavirus infection. Here we highlight some of the processes by which Ebola interacts with its mammalian hosts to evade anti-viral defenses.",,"['Misasi, John', 'Sullivan, Nancy J.']",,,,
,PMC,"An Observational, Laboratory-Based Study of Outbreaks of Middle East Respiratory Syndrome Coronavirus in Jeddah and Riyadh, Kingdom of Saudi Arabia, 2014",http://dx.doi.org/10.1093/cid/ciu812,PMC4303774,,,"Background. In spring 2014, a sudden rise in the number of notified Middle East respiratory syndrome coronavirus (MERS-CoV) infections occurred across Saudi Arabia with a focus in Jeddah. Hypotheses to explain the outbreak pattern include increased surveillance, increased zoonotic transmission, nosocomial transmission, and changes in viral transmissibility, as well as diagnostic laboratory artifacts. Methods. Diagnostic results from Jeddah Regional Laboratory were analyzed. Viruses from the Jeddah outbreak and viruses occurring during the same time in Riyadh, Al-Kharj, and Madinah were fully or partially sequenced. A set of 4 single-nucleotide polymorphisms distinctive to the Jeddah outbreak were determined from additional viruses. Viruses from Riyadh and Jeddah were isolated and studied in cell culture. Results. Up to 481 samples were received per day for reverse transcription polymerase chain reaction (RT-PCR) testing. A laboratory proficiency assessment suggested positive and negative results to be reliable. Forty-nine percent of 168 positive-testing samples during the Jeddah outbreak stemmed from King Fahd Hospital. All viruses from Jeddah were monophyletic and similar, whereas viruses from Riyadh were paraphyletic and diverse. A hospital-associated transmission cluster, to which cases in Indiana (United States) and the Netherlands belonged, was discovered in Riyadh. One Jeddah-type virus was found in Riyadh, with matching travel history to Jeddah. Virus isolates representing outbreaks in Jeddah and Riyadh were not different from MERS-CoV EMC/2012 in replication, escape of interferon response, or serum neutralization. Conclusions. Virus shedding and virus functions did not change significantly during the outbreak in Jeddah. These results suggest the outbreaks to have been caused by biologically unchanged viruses in connection with nosocomial transmission.",,"['Drosten, Christian', 'Muth, Doreen', 'Corman, Victor M.', 'Hussain, Raheela', 'Al Masri, Malaki', 'HajOmar, Waleed', 'Landt, Olfert', 'Assiri, Abdullah', 'Eckerle, Isabella', 'Al Shangiti, Ali', 'Al-Tawfiq, Jaffar A.', 'Albarrak, Ali', 'Zumla, Alimuddin', 'Rambaut, Andrew', 'Memish, Ziad A.']",,,,
,PMC,A comprehensive biophysical description of pairwise epistasis throughout an entire protein domain,http://dx.doi.org/10.1016/j.cub.2014.09.072,PMC4254498,,,"BACKGROUND: Non-additivity in fitness effects from two or more mutations, termed epistasis, can result in compensation of deleterious mutations or negation of beneficial mutations. Recent evidence shows the importance of epistasis in individual evolutionary pathways. However, an unresolved question in molecular evolution is how often and how significantly fitness effects change in alternative genetic backgrounds. RESULTS: To answer this question we quantified the effects of all single mutations and double mutations between all positions in the IgG-binding domain of protein G (GB1). By observing the first two steps of all possible evolutionary pathways, this fitness profile enabled the characterization of the extent and magnitude of pairwise epistasis throughout an entire protein molecule. Furthermore, we developed a novel approach to quantitatively determine the effects of single mutations on structural stability (ΔΔG(U)). This enabled determination of the importance of stability effects in functional epistasis. CONCLUSIONS: Our results illustrate common biophysical mechanisms for occurrences of positive and negative epistasis. Our results show pervasive positive epistasis within a conformationally dynamic network of residues. The stability analysis shows that significant negative epistasis, which is more common than positive epistasis, mostly occurs between combinations of destabilizing mutations. Furthermore, we show that although significant positive epistasis is rare, many deleterious mutations are beneficial in at least one alternative mutational background. The distribution of conditionally beneficial mutations throughout the domain demonstrates that the functional portion of sequence space can be significantly expanded by epistasis.",,"['Olson, C. Anders', 'Wu, Nicholas C.', 'Sun, Ren']",,,,
,PMC,Viral resistance of MOGS-CDG patients implies a broad-spectrum strategy against acute virus infections,http://dx.doi.org/10.3851/IMP2907,PMC4446249,,,"Sadat et al reported in the 2014 April 24 issue of New England Journal of Medicine that patients genetically deficient in the gene encoding mannosyl-oligosaccharide glucosidase (MOGS), also known as endoplasmic reticulum (ER) glucosidase I, manifested a severe hypogammaglobulinemia without clinical evidence of an infectious diathesis. This paradox phenomenon is, at least in part, because the impaired N-linked glycan processing of the patients compromises their ability to support efficient replication and cellular entry of viruses. This finding unambiguously validates ER glucosidases as valuable targets for antiviral agents against a broad-spectrum of enveloped viruses.",,"['Chang, Jinhong', 'Block, Timothy M.', 'Guo, Ju-Tao']",,,,
,PMC,Antibacterial activity and mechanism of action of Monarda punctata essential oil and its main components against common bacterial pathogens in respiratory tract,,PMC4270556,,,"The aim of the current research work was to study the chemical composition of the essential oil of Monarda punctata along with evaluating the essential oil and its major components for their antibacterial effects against some frequently encountered respiratory infection causing pathogens. Gas chromatographic mass spectrometric analysis revealed the presence of 13 chemical constituents with thymol (75.2%), p-cymene (6.7%), limonene (5.4), and carvacrol (3.5%) as the major constituents. The oil composition was dominated by the oxygenated monoterpenes. Antibacterial activity of the essential oil and its major constituents (thymol, p-cymene, limonene) was evaluated against Streptococcus pyogenes, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, Haemophilus influenzae and Escherichia coli. The study revealed that the essential oil and its constituents exhibited a broad spectrum and variable degree of antibacterial activity against different strains. Among the tested strains, Streptococcus pyogenes, Escherichia coli and Streptococcus pneumoniae were the most susceptible bacterial strain showing lowest MIC and MBC values. Methicillin-resistant Staphylococcus aureus was the most resistant bacterial strain to the essential oil treatment showing relatively higher MIC and MBC values. Scanning electron microscopy revealed that the essential oil induced potent and dose-dependent membrane damage in S. pyogenes and MRSA bacterial strains. The reactive oxygen species generated by the Monarda punctata essential oil were identified using 2’, 7’-dichlorofluorescein diacetate (DCFDA).This study indicated that the Monarda punctata essential oil to a great extent and thymol to a lower extent triggered a substantial increase in the ROS levels in S. pyogenes bacterial cultures which ultimately cause membrane damage as revealed by SEM results.",,"['Li, Hong', 'Yang, Tian', 'Li, Fei-Yan', 'Yao, Yan', 'Sun, Zhong-Min']",,,,
,PMC,Crystal Structure of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Papain-like Protease Bound to Ubiquitin Facilitates Targeted Disruption of Deubiquitinating Activity to Demonstrate Its Role in Innate Immune Suppression,http://dx.doi.org/10.1074/jbc.M114.609644,PMC4263872,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging human pathogen that was first isolated in 2012. MERS-CoV replication depends in part on a virus-encoded papain-like protease (PL(pro)) that cleaves the viral replicase polyproteins at three sites releasing non-structural protein 1 (nsp1), nsp2, and nsp3. In addition to this replicative function, MERS-CoV PL(pro) was recently shown to be a deubiquitinating enzyme (DUB) and to possess deISGylating activity, as previously reported for other coronaviral PL(pro) domains, including that of severe acute respiratory syndrome coronavirus. These activities have been suggested to suppress host antiviral responses during infection. To understand the molecular basis for ubiquitin (Ub) recognition and deconjugation by MERS-CoV PL(pro), we determined its crystal structure in complex with Ub. Guided by this structure, mutations were introduced into PL(pro) to specifically disrupt Ub binding without affecting viral polyprotein cleavage, as determined using an in trans nsp3↓4 cleavage assay. Having developed a strategy to selectively disable PL(pro) DUB activity, we were able to specifically examine the effects of this activity on the innate immune response. Whereas the wild-type PL(pro) domain was found to suppress IFN-β promoter activation, PL(pro) variants specifically lacking DUB activity were no longer able to do so. These findings directly implicate the DUB function of PL(pro), and not its proteolytic activity per se, in the inhibition of IFN-β promoter activity. The ability to decouple the DUB activity of PL(pro) from its role in viral polyprotein processing now provides an approach to further dissect the role(s) of PL(pro) as a viral DUB during MERS-CoV infection.",,"['Bailey-Elkin, Ben A.', 'Knaap, Robert C. M.', 'Johnson, Garrett G.', 'Dalebout, Tim J.', 'Ninaber, Dennis K.', 'van Kasteren, Puck B.', 'Bredenbeek, Peter J.', 'Snijder, Eric J.', 'Kikkert, Marjolein', 'Mark, Brian L.']",,,,
,PMC,Innate receptors and cellular defense against pulmonary infections,http://dx.doi.org/10.4049/jimmunol.1400978,PMC4185409,,,"In the United States, mortality as a result of lung infections consistently ranks in the top ten leading causes of death, accounting for over 50,000 deaths annually. Moreover, there are more than 140,000 deaths annually as a result of chronic lung diseases, some of which may be complicated by an infectious process. The lung is constantly exposed to the environment and consequently, susceptible to infectious complications caused by bacterial, viral, fungal and parasitic pathogens. Indeed, we are continually faced with the threat of morbidity and mortality associated with annual influenza virus infections, new respiratory viruses (such as SARS-CoV) as well as lung infections caused by antibiotic-resistant “ESKAPE pathogens” (three of which target the lung). This review will highlight innate immune receptors and cell types that function to protect against infectious challenges to the respiratory system yet may also be associated with exacerbations in chronic lung diseases.",,"['Werner, Jessica L.', 'Steele, Chad']",,,,
,PMC,On the Quarantine Period for Ebola Virus,http://dx.doi.org/10.1371/currents.outbreaks.2ab4b76ba7263ff0f084766e43abbd89,PMC4205154,25642371,CC BY,"Background: 21 days has been regarded as the appropriate quarantine period for holding individuals potentially exposed to Ebola Virus (EV) to reduce risk of contagion. There does not appear to be a systematic discussion of the basis for this period. Methods: The prior estimates for incubation time to EV were examined, along with data on the first 9 months of the current outbreak. These provided estimates of the distribution of incubation times. Results: A 21 day period for quarantine may result in the release of individuals with a 0.2 - 12% risk of release prior to full opportunity for the incubation to proceed. It is suggested that a detailed cost-benefit assessment, including considering full transmission risks, needs to occur in order to determine the appropriate quarantine period for potentially exposed individuals.",2014 Oct 14,"Haas, Charles N.",PLoS Curr,,,
,PMC,Domesticated transposase Kat1 and its fossil imprints induce sexual differentiation in yeast,http://dx.doi.org/10.1073/pnas.1406027111,PMC4217401,,,"Transposable elements (TEs) have had a major influence on shaping both prokaryotic and eukaryotic genomes, largely through stochastic events following random or near-random insertions. In the mammalian immune system, the recombination activation genes1/2 (Rag1/2) recombinase has evolved from a transposase gene, demonstrating that TEs can be domesticated by the host. In this study, we uncovered a domesticated transposase, Kluyveromyces lactis hobo/Activator/Tam3 (hAT) transposase 1 (Kat1), operating at the fossil imprints of an ancient transposon, that catalyzes the differentiation of cell type. Kat1 induces mating-type switching from mating type a (MATa) to MATα in the yeast K. lactis. Kat1 activates switching by introducing two hairpin-capped DNA double-strand breaks (DSBs) in the MATa1–MATa2 intergenic region, as we demonstrate both in vivo and in vitro. The DSBs stimulate homologous recombination with the cryptic hidden MAT left alpha (HMLα) locus resulting in a switch of the cell type. The sites where Kat1 acts in the MATa locus most likely are ancient remnants of terminal inverted repeats from a long-lost TE. The KAT1 gene is annotated as a pseudogene because it contains two overlapping ORFs. We demonstrate that translation of full-length Kat1 requires a programmed −1 frameshift. The frameshift limited Kat1 activity, because restoring the zero frame causes switching to the MATα genotype. Kat1 also was transcriptionally activated by nutrient limitation via the transcription factor mating type switch 1 (Mts1). A phylogenetic analysis indicated that KAT1 was domesticated specifically in the Kluyveromyces clade of the budding yeasts. We conclude that Kat1 is a highly regulated transposase-derived endonuclease vital for sexual differentiation.",,"['Rajaei, Naghmeh', 'Chiruvella, Kishore K.', 'Lin, Feng', 'Åström, Stefan U.']",,,,
,PMC,CEACAM2 negatively regulates hemi (ITAM-bearing) GPVI and CLEC-2 pathways and thrombus growth in vitro and in vivo,http://dx.doi.org/10.1182/blood-2014-04-569707,PMC4192753,,,"Carcinoembryonic antigen–related cell adhesion molecule-2 (CEACAM2) is a cell-surface glycoprotein expressed on blood, epithelial, and vascular cells. CEACAM2 possesses adhesive and signaling properties mediated by immunoreceptor tyrosine-based inhibitory motifs. In this study, we demonstrate that CEACAM2 is expressed on the surface and in intracellular pools of platelets. Functional studies of platelets from Ceacam2(−/−)-deficient mice (Cc2(−/−)) revealed that CEACAM2 serves to negatively regulate collagen glycoprotein VI (platelet) (GPVI)-FcRγ–chain and the C-type lectinlike receptor 2 (CLEC-2) signaling. Cc2(−/−) platelets displayed enhanced GPVI and CLEC-2–selective ligands, collagen-related peptide (CRP), collagen, and rhodocytin (Rhod)-mediated platelet aggregation. They also exhibited increased adhesion on type I collagen, and hyperresponsive CRP and CLEC-2–induced α and dense granule release compared with wild-type platelets. Furthermore, using intravital microscopy to ferric chloride (FeCl(3))–injured mesenteric arterioles and laser-induced injury of cremaster muscle arterioles, we herein show that thrombi formed in Cc2(−/−) mice were larger and more stable than wild-type controls in vivo. Thus, CEACAM2 is a novel platelet immunoreceptor that acts as a negative regulator of platelet GPVI-collagen interactions and of ITAM receptor CLEC-2 pathways.",,"['Alshahrani, Musaed M.', 'Yang, Eunice', 'Yip, Jana', 'Ghanem, Simona S.', 'Abdallah, Simon L.', 'deAngelis, Anthony M.', 'O’Malley, Cindy J.', 'Moheimani, Fatemeh', 'Najjar, Sonia M.', 'Jackson, Denise E.']",,,,
,PMC,"Synthesizing data and models for the spread of MERS-CoV, 2013: key role of index cases and hospital transmission",http://dx.doi.org/10.1016/j.epidem.2014.09.011,PMC4258236,,,"The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 209 deaths and 699 laboratory-confirmed cases in the Arabian Peninsula as of June 11, 2014. Preparedness efforts are hampered by considerable uncertainty about the nature and intensity of human-to-human transmission, with previous reproduction number estimates ranging from 0.4 to 1.5. Here we synthesize epidemiological data and transmission models for the MERS-CoV outbreak during April-October 2013 to resolve uncertainties in epidemic risk, while considering the impact of observation bias. We match the progression of MERS-CoV cases in 2013 to a dynamic transmission model that incorporates community and hospital compartments, and distinguishes transmission by zoonotic (index) cases and secondary cases. When observation bias is assumed to account for the fact that all reported zoonotic cases are severe, but only ~57% of secondary cases are symptomatic, the average reproduction number of MERS-CoV is estimated to be 0.45 (95%CI:0.29–0.61). Alternatively, if these epidemiological observations are taken at face value, index cases are estimated to transmit substantially more effectively than secondary cases, (R(i) =0.84 (0.58–1.20) vs R(s)=0.36 (0.24–0.51)). In both scenarios the relative contribution of hospital-based transmission is over four times higher than that of community transmission, indicating that disease control should be focused on hospitalized patients. Adjusting previously published estimates for observation bias confirms a strong support for the average R < 1 in the first stage of the outbreak in 2013 and thus, transmissibility of secondary cases of MERS-CoV remained well below the epidemic threshold. More information on the observation process is needed to clarify whether MERS-CoV is intrinsically weakly transmissible between people or whether existing control measures have contributed meaningfully to reducing the transmissibility of secondary cases. Our results could help evaluate the progression of MERS-CoV in recent months in response to changes in disease surveillance, control interventions, or viral adaptation.",,"['Chowell, Gerardo', 'Blumberg, Seth', 'Simonsen, Lone', 'Miller, Mark A.', 'Viboud, Cécile']",,,,
,PMC,"Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein",http://dx.doi.org/10.1073/pnas.1407087111,PMC4210292,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly identified betacoronavirus causing high morbidity and mortality in humans. The coronavirus spike (S) protein is the main determinant of viral entry, and although it was previously shown that MERS-CoV S can be activated by various proteases, the details of the mechanisms of proteolytic activation of fusion are still incompletely characterized. Here, we have uncovered distinctive characteristics of MERS-CoV S. We identify, by bioinformatics and peptide cleavage assays, two cleavage sites for furin, a ubiquitously expressed protease, which are located at the S1/S2 interface and at the S2′ position of the S protein. We show that although the S1/S2 site is proteolytically processed by furin during protein biosynthesis, the S2′ site is cleaved upon viral entry. MERS-CoV pseudovirion infection was shown to be enhanced by elevated levels of furin expression, and entry could be decreased by furin siRNA silencing. Enhanced furin activity appeared to partially override the low pH-dependent nature of MERS-CoV entry. Inhibition of furin activity was shown to decrease MERS-CoV S-mediated entry, as well as infection by the virus. Overall, we show that MERS-CoV has evolved an unusual two-step furin activation for fusion, suggestive of a role during the process of emergence into the human population. The ability of MERS-CoV to use furin in this manner, along with other proteases, may explain the polytropic nature of the virus.",,"['Millet, Jean Kaoru', 'Whittaker, Gary R.']",,,,
,PMC,Design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets,http://dx.doi.org/10.1002/pro.2578,PMC4380977,,,"Ebolaviruses are highly lethal filoviruses that cause hemorrhagic fever in humans and nonhuman primates. With no approved treatments or preventatives, the development of an anti-ebolavirus therapy to protect against natural infections and potential weaponization is an urgent global health need. Here, we describe the design, biophysical characterization, and validation of peptide mimics of the ebolavirus N-trimer, a highly conserved region of the GP2 fusion protein, to be used as targets to develop broad-spectrum inhibitors of ebolavirus entry. The N-trimer region of GP2 is 90% identical across all ebolavirus species and forms a critical part of the prehairpin intermediate that is exposed during viral entry. Specifically, we fused designed coiled coils to the N-trimer to present it as a soluble trimeric coiled coil as it appears during membrane fusion. Circular dichroism, sedimentation equilibrium, and X-ray crystallography analyses reveal the helical, trimeric structure of the designed N-trimer mimic targets. Surface plasmon resonance studies validate that the N-trimer mimic binds its native ligand, the C-peptide region of GP2. The longest N-trimer mimic also inhibits virus entry, thereby confirming binding of the C-peptide region during viral entry and the presence of a vulnerable prehairpin intermediate. Using phage display as a model system, we validate the suitability of the N-trimer mimics as drug screening targets. Finally, we describe the foundational work to use the N-trimer mimics as targets in mirror-image phage display, which will be used to identify d-peptide inhibitors of ebolavirus entry.",,"['Clinton, Tracy R', 'Weinstock, Matthew T', 'Jacobsen, Michael T', 'Szabo-Fresnais, Nicolas', 'Pandya, Maya J', 'Whitby, Frank G', 'Herbert, Andrew S', 'Prugar, Laura I', 'McKinnon, Rena', 'Hill, Christopher P', 'Welch, Brett D', 'Dye, John M', 'Eckert, Debra M', 'Kay, Michael S']",,,,
,PMC,Gut microbiome and the risk factors in central nervous system autoimmunity,http://dx.doi.org/10.1016/j.febslet.2014.09.024,PMC4254300,,,"Humans are colonized after birth by microbial organisms that form a heterogeneous community, collectively termed microbiota. The genomic pool of this macro-community is named microbiome. The gut microbiota is essential for the complete development of the immune system, representing a binary system in which the microbiota interact with the host providing important immune and physiologic function and conversely the bacteria protect themselves from host immune defense. Alterations in the balance of the gut microbiome due to a combination of environmental and genetic factors can now be associated with detrimental or protective effects in experimental autoimmune diseases. These gut microbiome alterations can unbalance the gastrointestinal immune responses and influence distal effector immune sites leading to CNS disease including both demyelination and affective disorders. The current range of risk factors for MS includes genetic makeup and environmental elements. Of interest to this review is the consistency between this range of MS risk factors and the gut microbiome. We postulate that the gut microbiome serves as the niche where different MS risk factors merge, thereby influencing the disease process.",,"['Ochoa-Repáraz, Javier', 'Kasper, Lloyd H']",,,,
,PMC,Evidence of MAPK–JNK1/2 activation by hepatitis E virus ORF3 protein in cultured hepatoma cells,http://dx.doi.org/10.1007/s10616-014-9785-1,PMC4371560,,,"Hepatitis E virus (HEV) has recently emerged to cause chronic infection in some immunosuppressed individuals, including extrahepatic manifestations in acute and chronic patients. Mammalian MAPK–JNK1/2 is expressed in hepatocytes, which is known to be involved in anti-apoptotic signaling pathway for the establishment of persistent infection. Though in vitro modulation of cellular MAPK–ERK cascade by HEV-ORF3 protein is suggested to have a role in host pathobiology, activation of the JNK module has not been studied so far. In this report, we have shown for the first time, evidence of MAPK–JNK1/2 activation by HEV-ORF3, using viral replicon as well as expression vector in human hepatoma cells. Phospho-ELISA based relative quantitaion has demonstrated ~54% and ~66% phosphorylation of JNK1/2 in replicon-RNA and ORF3-vector DNA transfected cells, respectively. Our finding however, suggests further molecular studies to validate a role of JNK1/2 in HEV pathogenesis.",,"['Parvez, Mohammad Khalid', 'Al-Dosari, Mohammed Salem']",,,,
,PMC,Barcode-Enabled Sequencing of Plasmablast Antibody Repertoires in Rheumatoid Arthritis,http://dx.doi.org/10.1002/art.38754,PMC4560105,,,"OBJECTIVE: A hallmark of rheumatoid arthritis (RA) is the production of autoantibodies, including anti-citrullinated protein antibodies (ACPAs). Nevertheless, the specific targets of these autoantibodies remain incompletely defined. During an immune response, B cells specific for the inciting antigen(s) are activated and differentiate into “plasmablasts”, which are released into the blood. In this study we sequence the plasmablast antibody repertoire to define the targets of the active immune response in RA. METHODS: We developed a novel DNA barcoding method to sequence the cognate heavy- and light-chain pairs of antibodies expressed by individual blood plasmablasts in RA. The method uses a universal 5’ adapter that enables full-length sequencing of the antibodies’ variable regions and recombinant expression of the paired antibody chains. The sequence datasets were bioinformatically analyzed to generate phylogenetic trees that identify clonal families of antibodies sharing heavy- and light-chain VJ sequences. Representative antibodies were expressed, and their binding properties characterized using CCP2 ELISA and antigen microarrays. RESULTS: We used our sequencing method to generate phylogenetic trees representing the antibody repertoires of peripheral blood plasmablasts of 4 individuals with anti-CCP(+) RA, and recombinantly expressed 14 antibodies that were either “singleton” antibodies or representative of clonal antibody families. CCP2 ELISA identified four ACPAs, and antigen microarray analysis identified ACPAs that differentially targeted epitopes on α-enolase, citrullinated fibrinogen, and citrullinated histone 2B. CONCLUSIONS: Our data provide evidence that autoantibodies targeting α-enolase, citrullinated fibrinogen, and citrullinated histone 2B are produced by the ongoing activated B cell response in, and thus may contribute to the pathogenesis of, RA.",,"['Tan, Yann-Chong', 'Kongpachith, Sarah', 'Blum, Lisa K.', 'Ju, Chia-Hsin', 'Lahey, Lauren J.', 'Lu, Dan R.', 'Cai, Xiaoyong', 'Wagner, Catriona A.', 'Lindstrom, Tamsin M.', 'Sokolove, Jeremy', 'Robinson, William H.']",,,,
,PMC,The leader proteinase of foot-and-mouth disease virus: structure-function relationships in a proteolytic virulence factor,http://dx.doi.org/10.1515/hsz-2014-0156,PMC4931897,,,"The leader proteinase (L(pro)) of foot-and-mouth disease virus, inhibits the host innate immune response by at least three different mechanisms. The most well characterised is the prevention of the synthesis of cytokines such as interferons immediately after infection, brought about by specific proteolytic cleavage of the eukaryotic initiation factor 4G. This prevents the recruitment of capped cellular mRNA; the viral RNA can however be translated under these conditions. The two other mechanisms are the induction of NF-κB cleavage and the deubiquitination of immune signalling molecules. This review focuses on the structure-function relationships in L(pro) responsible for these widely divergent activities.",,"['Steinberger, Jutta', 'Skern, Tim']",,,,
,PMC,How infectious disease outbreaks affect community-based primary care physicians: Comparing the SARS and H1N1 epidemics,,PMC4196817,,,"OBJECTIVE: To compare how the infectious disease outbreaks H1N1 and severe acute respiratory syndrome (SARS) affected community-based GPs and FPs. DESIGN: A mailed survey sent after the H1N1 outbreak compared with the results of similar survey completed after the SARS outbreak. SETTING: Greater Toronto area in Ontario. PARTICIPANTS: A total of 183 randomly selected GPs and FPs who provided office-based care. MAIN OUTCOME MEASURES: The perceptions of GPs and FPs on how serious infectious disease outbreaks affected their clinical work and personal lives; their preparedness for a serious infectious disease outbreak; and the types of information they want to receive and the sources they wanted to receive information from during a serious infectious disease outbreak. The responses from this survey were compared with the responses of GPs and FPs in the greater Toronto area who completed a similar survey in 2003 after the SARS outbreak. RESULTS: After the H1N1 outbreak, GPs and FPs still had substantial concerns about the effects of serious infectious disease outbreaks on the health of their family members. Physicians made changes to various office practices in order to manage and deal with patients with serious infectious diseases. They expressed concerns about the effects of an infectious disease on the provision of health care services. Also, physicians wanted to quickly receive accurate information from the provincial government and their medical associations. CONCLUSION: Serious community-based infectious diseases are a personal concern for GPs and FPs, and have considerable effects on their clinical practice. Further work examining the timely flow of relevant information through different health care sectors and government agencies still needs to be undertaken.",,"['Jaakkimainen, R. Liisa', 'Bondy, Susan J.', 'Parkovnick, Meredith', 'Barnsley, Jan']",,,,
,PMC,Virtues and values in medicine revisited: individual and global health,http://dx.doi.org/10.7861/clinmedicine.14-5-495,PMC4951957,,,"In response to the call from an international panel for ‘much needed rethinking’ about the goals and purposes of the education of healthcare professionals, we suggest that there must be an explicit account of the virtues and values that will inform healthcare practice in the 21st century. We propose that a renewed emphasis is needed on reviving the well-honed clinical skills and humanistic attributes in medicine as crucial for optimum affordable (and sustainable) care of individual patients. Analogous virtues should be linked to the quest for improving the health of whole populations, nationally and globally.",,"['Benatar, Solomon', 'Upshur, Ross']",,,,
,PMC,Clinical Microbiology Informatics,http://dx.doi.org/10.1128/CMR.00049-14,PMC4187636,,,"SUMMARY: The clinical microbiology laboratory has responsibilities ranging from characterizing the causative agent in a patient's infection to helping detect global disease outbreaks. All of these processes are increasingly becoming partnered more intimately with informatics. Effective application of informatics tools can increase the accuracy, timeliness, and completeness of microbiology testing while decreasing the laboratory workload, which can lead to optimized laboratory workflow and decreased costs. Informatics is poised to be increasingly relevant in clinical microbiology, with the advent of total laboratory automation, complex instrument interfaces, electronic health records, clinical decision support tools, and the clinical implementation of microbial genome sequencing. This review discusses the diverse informatics aspects that are relevant to the clinical microbiology laboratory, including the following: the microbiology laboratory information system, decision support tools, expert systems, instrument interfaces, total laboratory automation, telemicrobiology, automated image analysis, nucleic acid sequence databases, electronic reporting of infectious agents to public health agencies, and disease outbreak surveillance. The breadth and utility of informatics tools used in clinical microbiology have made them indispensable to contemporary clinical and laboratory practice. Continued advances in technology and development of these informatics tools will further improve patient and public health care in the future.",,"['Rhoads, Daniel D.', 'Sintchenko, Vitali', 'Rauch, Carol A.', 'Pantanowitz, Liron']",,,,
,PMC,"Emerging and Reemerging Neglected Tropical Diseases: a Review of Key Characteristics, Risk Factors, and the Policy and Innovation Environment",http://dx.doi.org/10.1128/CMR.00045-14,PMC4187634,,,"SUMMARY: In global health, critical challenges have arisen from infectious diseases, including the emergence and reemergence of old and new infectious diseases. Emergence and reemergence are accelerated by rapid human development, including numerous changes in demographics, populations, and the environment. This has also led to zoonoses in the changing human-animal ecosystem, which are impacted by a growing globalized society where pathogens do not recognize geopolitical borders. Within this context, neglected tropical infectious diseases have historically lacked adequate attention in international public health efforts, leading to insufficient prevention and treatment options. This subset of 17 infectious tropical diseases disproportionately impacts the world's poorest, represents a significant and underappreciated global disease burden, and is a major barrier to development efforts to alleviate poverty and improve human health. Neglected tropical diseases that are also categorized as emerging or reemerging infectious diseases are an even more serious threat and have not been adequately examined or discussed in terms of their unique risk characteristics. This review sets out to identify emerging and reemerging neglected tropical diseases and explore the policy and innovation environment that could hamper or enable control efforts. Through this examination, we hope to raise awareness and guide potential approaches to addressing this global health concern.",,"['Mackey, Tim K.', 'Liang, Bryan A.', 'Cuomo, Raphael', 'Hafen, Ryan', 'Brouwer, Kimberly C.', 'Lee, Daniel E.']",,,,
,PMC,Pathogenesis of Human Diffusely Adhering Escherichia coli Expressing Afa/Dr Adhesins (Afa/Dr DAEC): Current Insights and Future Challenges,http://dx.doi.org/10.1128/CMR.00036-14,PMC4187631,,,"SUMMARY: The pathogenicity and clinical pertinence of diffusely adhering Escherichia coli expressing the Afa/Dr adhesins (Afa/Dr DAEC) in urinary tract infections (UTIs) and pregnancy complications are well established. In contrast, the implication of intestinal Afa/Dr DAEC in diarrhea is still under debate. These strains are age dependently involved in diarrhea in children, are apparently not involved in diarrhea in adults, and can also be asymptomatic intestinal microbiota strains in children and adult. This comprehensive review analyzes the epidemiology and diagnosis and highlights recent progress which has improved the understanding of Afa/Dr DAEC pathogenesis. Here, I summarize the roles of Afa/Dr DAEC virulence factors, including Afa/Dr adhesins, flagella, Sat toxin, and pks island products, in the development of specific mechanisms of pathogenicity. In intestinal epithelial polarized cells, the Afa/Dr adhesins trigger cell membrane receptor clustering and activation of the linked cell signaling pathways, promote structural and functional cell lesions and injuries in intestinal barrier, induce proinflammatory responses, create angiogenesis, instigate epithelial-mesenchymal transition-like events, and lead to pks-dependent DNA damage. UTI-associated Afa/Dr DAEC strains, following adhesin-membrane receptor cell interactions and activation of associated lipid raft-dependent cell signaling pathways, internalize in a microtubule-dependent manner within urinary tract epithelial cells, develop a particular intracellular lifestyle, and trigger a toxin-dependent cell detachment. In response to Afa/Dr DAEC infection, the host epithelial cells generate antibacterial defense responses. Finally, I discuss a hypothetical role of intestinal Afa/Dr DAEC strains that can act as “silent pathogens” with the capacity to emerge as “pathobionts” for the development of inflammatory bowel disease and intestinal carcinogenesis.",,"Servin, Alain L.",,,,
,PMC,Partial Activation of Natural Killer and γδ T Cells by Classical Swine Fever Viruses Is Associated with Type I Interferon Elicited from Plasmacytoid Dendritic Cells,http://dx.doi.org/10.1128/CVI.00382-14,PMC4266346,,,"Vaccination with live attenuated classical swine fever virus (CSFV) vaccines can rapidly confer protection in the absence of neutralizing antibodies. With an aim of providing information on the cellular mechanisms that may mediate this protection, we explored the interaction of porcine natural killer (NK) cells and γδ T cells with CSFV. Both NK and γδ T cells were refractory to infection with attenuated or virulent CSFV, and no stimulatory effects, as assessed by the expression of major histocompatibility complex (MHC) class II (MHC-II), perforin, and gamma interferon (IFN-γ), were observed when the cells were cultured in the presence of CSFV. Coculture with CSFV and myeloid dendritic cells (mDCs) or plasmacytoid dendritic cells (pDCs) showed that pDCs led to a partial activation of both NK and γδ T cells, with upregulation of MHC-II being observed. An analysis of cytokine expression by infected DC subsets suggested that this effect was due to IFN-α secreted by infected pDCs. These results were supported by ex vivo analyses of NK and γδ T cells in the tonsils and retropharyngeal lymph nodes from pigs that had been vaccinated with live attenuated CSFV and/or virulent CSFV. At 5 days postchallenge, there was evidence of significant upregulation of MHC-II but not perforin on NK and γδ T cells, which was observed only following a challenge of the unvaccinated pigs and correlated with increased CSFV replication and IFN-α expression in both the tonsils and serum. Together, these data suggest that it is unlikely that NK or γδ T cells contribute to the cellular effector mechanisms induced by live attenuated CSFV.",,"['Franzoni, Giulia', 'Edwards, Jane C.', 'Kurkure, Nitin V.', 'Edgar, Daniel S.', 'Sanchez-Cordon, Pedro J.', 'Haines, Felicity J.', 'Salguero, Francisco J.', 'Everett, Helen E.', 'Bodman-Smith, Kikki B.', 'Crooke, Helen R.', 'Graham, Simon P.']",,,,
,PMC,Micromelic Dysplasia-Like Syndrome in a Captive Colony of Common Marmosets (Callithrix jacchus),,PMC4236788,,,"Over several years, 0% to 5% of adolescent animals in a captive colony of common marmosets (Callithrix jacchus) showed severely bended arms and legs over several years. The animals showed no pain, discomfort, or altered behavior but were unable to stretch their distal limbs to their full extent. To characterize the lesion morphologically, the bones of 4 affected marmosets were compared macroscopically and radiographically with those of 6 unaffected animals. The deformities were characterized by mid- to distal diaphyseal bending and pronounced shortening of long bones. The morphology and density of other bones including the skull and vertebrae were unaffected. Although vitamin D values were low in a fifth affected marmoset during 10 to 16 mo of age, lesions associated with rickets were not observed. To our knowledge, this report is the first to describe a micromelic dysplasia-like syndrome comprising severe, idiopathic bending and shortening of long bones in a colony of marmosets.",,"['Bosseler, Leslie', 'Cornillie, Pieter', 'Saunders, Jimmy H', 'Bakker, Jaco', 'Langermans, Jan AM', 'Casteleyn, Christophe', 'Decostere, Annemie', 'Chiers, Koen']",,,,
,PMC,Interaction of pathogens with host cholesterol metabolism,http://dx.doi.org/10.1097/MOL.0000000000000106,PMC4219984,,,"PURPOSE OF THE REVIEW: Pathogens of different taxa, from prions to protozoa, target cellular cholesterol metabolism to advance own development and to impair host immune responses, but also causing metabolic complications, e.g. atherosclerosis. This review describes recent findings of how pathogens do it. RECENT FINDINGS: A common theme in interaction between pathogens and host cholesterol metabolism is pathogens targeting lipid rafts of the host plasma membrane. Many intracellular pathogens use rafts as an entry gate, taking advantage of the endocytic machinery and high abundance of outward looking molecules that can be used as receptors. At the same time, disruption of the rafts’ functional capacity, achieved by the pathogens through a number of various means, impairs the ability of the host to generate immune response, thus helping pathogen to thrive. Pathogens cannot synthesise cholesterol, and salvaging host cholesterol helps pathogens build advanced cholesterol-containing membranes and assembly platforms. Impact on cholesterol metabolism is not limited to the infected cells; proteins and miRNAs secreted by infected cells affect lipid metabolism systemically. SUMMARY: Given an essential role that host cholesterol metabolism plays in pathogen development, targeting this interaction may be a viable strategy to fight infections as well as metabolic complications of the infections.",,"['Sviridov, Dmitri', 'Bukrinsky, Michael']",,,,
,PMC,Promoting remyelination: utilizing a viral model of demyelination to assess cell-based therapies,http://dx.doi.org/10.1586/14737175.2014.955854,PMC4232205,,,"Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS. While a broad range of therapeutics effectively reduce the incidence of focal white matter inflammation and plaque formation for patients with relapse-remitting forms of MS, a challenge within the field is to develop therapies that allow for axonal protection and remyelination. In the last decade, growing interest has focused on utilizing neural precursor cells (NPCs) to promote remyelination. To understand how NPCs function in chronic demyelinating environments, several excellent pre-clinical mouse models have been developed. One well accepted model is infection of susceptible mice with neurotropic variants of mouse hepatitis virus (MHV) that undergo chronic demyelination exhibiting clinical and histopathologic similarities to MS patients. Combined with the possibility that an environmental agent such as a virus could trigger MS, the MHV model of demyelination presents a relevant mouse model to assess the therapeutic potential of NPCs transplanted into an environment in which inflammatory-mediated demyelination is established.",,"['Marro, Brett S', 'Blanc, Caroline A', 'Loring, Jeanne F', 'Cahalan, Michael D', 'Lane, Thomas E']",,,,
,PMC,Exploring the Potential of Next-Generation Sequencing in Detection of Respiratory Viruses,http://dx.doi.org/10.1128/JCM.01641-14,PMC4187785,,,"Efficient detection of human respiratory viral pathogens is crucial in the management of patients with acute respiratory tract infection. Sequence-independent amplification of nucleic acids combined with next-generation sequencing technology and bioinformatics analyses is a promising strategy for identifying pathogens in clinical and public health settings. It allows the characterization of hundreds of different known pathogens simultaneously and of novel pathogens that elude conventional testing. However, major hurdles for its routine use exist, including cost, turnaround time, and especially sensitivity of the assay, as the detection limit is dependent on viral load, host genetic material, and sequencing depth. To obtain insights into these aspects, we analyzed nasopharyngeal aspirates from a cohort of 81 Thai children with respiratory disease for the presence of respiratory viruses using a sequence-independent next-generation sequencing approach and routinely used diagnostic real-time reverse transcriptase PCR (real-time RT-PCR) assays. With respect to the detection of rhinovirus and human metapneumovirus, the next-generation sequencing approach was at least as sensitive as diagnostic real-time RT-PCR in this small cohort, whereas for bocavirus and enterovirus, next-generation sequencing was less sensitive than real-time RT-PCR. The advantage of the sequencing approach over real-time RT-PCR was the immediate availability of virus-typing information. Considering the development of platforms capable of generating more output data at declining costs, next-generation sequencing remains of interest for future virus diagnosis in clinical and public health settings and certainly as an additional tool when screening results from real-time RT-PCR are negative.",,"['Prachayangprecha, Slinporn', 'Schapendonk, Claudia M. E.', 'Koopmans, Marion P.', 'Osterhaus, Albert D. M. E.', 'Schürch, Anita C.', 'Pas, Suzan D.', 'van der Eijk, Annemiek A.', 'Poovorawan, Yong', 'Haagmans, Bart L.', 'Smits, Saskia L.']",,,,
,PMC,Detection of Respiratory Viruses in Sputum from Adults by Use of Automated Multiplex PCR,http://dx.doi.org/10.1128/JCM.01523-14,PMC4187748,,,"Respiratory tract infections (RTI) frequently cause hospital admissions among adults. Diagnostic viral reverse transcriptase PCR (RT-PCR) of nose and throat swabs (NTS) is useful for patient care by informing antiviral use and appropriate isolation. However, automated RT-PCR systems are not amenable to utilizing sputum due to its viscosity. We evaluated a simple method of processing sputum samples in a fully automated respiratory viral panel RT-PCR assay (FilmArray). Archived sputum and NTS samples collected in 2008-2012 from hospitalized adults with RTI were evaluated. A subset of sputum samples positive for 10 common viruses by a uniplex RT-PCR was selected. A sterile cotton-tip swab was dunked in sputum, swirled in 700 μL of sterile water (dunk and swirl method) and tested by the FilmArray assay. Quantitative RT-PCR was performed on “dunked” sputum and NTS samples for influenza A (Flu A), respiratory syncytial virus (RSV), coronavirus OC43 (OC43), and human metapneumovirus (HMPV). Viruses were identified in 31% of 965 illnesses using a uniplex RT-PCR. The sputum sample was the only sample positive for 105 subjects, including 35% (22/64) of influenza cases and significantly increased the diagnostic yield of NTS alone (302/965 [31%] versus 197/965 [20%]; P = 0.0001). Of 108 sputum samples evaluated by the FilmArray assay using the dunk and swirl method, 99 (92%) were positive. Quantitative RT-PCR revealed higher mean viral loads in dunked sputum samples compared to NTS samples for Flu A, RSV, and HMPV (P = 0.0001, P = 0.006, and P = 0.011, respectively). The dunk and swirl method is a simple and practical method for reliably processing sputum samples in a fully automated PCR system. The higher viral loads in sputa may increase detection over NTS testing alone.",,"['Branche, Angela R.', 'Walsh, Edward E.', 'Formica, Maria A.', 'Falsey, Ann R.']",,,,
,PMC,"Fatal Systemic Necrotizing Infections Associated with a Novel Paramyxovirus, Anaconda Paramyxovirus, in Green Anaconda Juveniles",http://dx.doi.org/10.1128/JCM.01653-14,PMC4187747,,,"Beginning in July 2011, 31 green anaconda (Eunectes murinus) juveniles from an oceanarium in Hong Kong died over a 12-month period. Necropsy revealed at least two of the following features in 23 necropsies: dermatitis, severe pan-nephritis, and/or severe systemic multiorgan necrotizing inflammation. Histopathological examination revealed severe necrotizing inflammation in various organs, most prominently the kidneys. Electron microscopic examination of primary tissues revealed intralesional accumulations of viral nucleocapsids with diameters of 10 to 14 nm, typical of paramyxoviruses. Reverse transcription (RT)-PCR results were positive for paramyxovirus (viral loads of 2.33 × 10(4) to 1.05 × 10(8) copies/mg tissue) in specimens from anaconda juveniles that died but negative in specimens from the two anaconda juveniles and anaconda mother that survived. None of the other snakes in the park was moribund, and RT-PCR results for surveillance samples collected from other snakes were negative. The virus was isolated from BHK21 cells, causing cytopathic effects with syncytial formation. The virus could also replicate in 25 of 27 cell lines of various origins, in line with its capability for infecting various organs. Electron microscopy with cell culture material revealed enveloped virus with the typical “herringbone” appearance of helical nucleocapsids in paramyxoviruses. Complete genome sequencing of five isolates confirmed that the infections originated from the same clone. Comparative genomic and phylogenetic analyses and mRNA editing experiments revealed a novel paramyxovirus in the genus Ferlavirus, named anaconda paramyxovirus, with a typical Ferlavirus genomic organization of 3′-N-U-P/V/I-M-F-HN-L-5′. Epidemiological and genomic analyses suggested that the anaconda juveniles acquired the virus perinatally from the anaconda mother rather than from other reptiles in the park, with subsequent interanaconda juvenile transmission.",,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Martelli, Paolo', 'Hui, Suk-Wai', 'Lau, Candy C. Y.', 'Fan, Rachel Y. Y.', 'Groff, Joseph M.', 'Tam, Emily W. T.', 'Chan, Kwok-Hung', 'Yuen, Kwok-Yung']",,,,
,PMC,The Emergence of Ebola as a Global Health Security Threat: From ‘Lessons Learned’ to Coordinated Multilateral Containment Efforts,http://dx.doi.org/10.4103/0974-777X.145247,PMC4265832,25538455,CC BY-NC-SA,"First reported in remote villages of Africa in the 1970s, the Ebolavirus was originally believed to be transmitted to people from wild animals. Ebolavirus (EBOV) causes a severe, frequently fatal hemorrhagic syndrome in humans. Each outbreak of the Ebolavirus over the last three decades has perpetuated fear and economic turmoil among the local and regional populations in Africa. Until now it has been considered a tragic malady confined largely to the isolated regions of the African continent, but it is no longer so. The frequency of outbreaks has increased since the 1970s. The 2014 Ebola outbreak in Western Africa has been the most severe in history and was declared a public health emergency by the World Health Organization. Given the widespread use of modern transportation and global travel, the EBOV is now a risk to the entire Global Village, with intercontinental transmission only an airplane flight away. Clinically, symptoms typically appear after an incubation period of approximately 11 days. A flu-like syndrome can progress to full hemorrhagic fever with multiorgan failure, and frequently, death. Diagnosis is confirmed by detection of viral antigens or Ribonucleic acid (RNA) in the blood or other body fluids. Although historically the mortality of this infection exceeded 80%, modern medicine and public health measures have been able to lower this figure and reduce the impact of EBOV on individuals and communities. The treatment involves early, aggressive supportive care with rehydration. Core interventions, including contact tracing, preventive initiatives, active surveillance, effective isolation and quarantine procedures, and timely response to patients, are essential for a successful outbreak control. These measures, combined with public health education, point-of-care diagnostics, promising new vaccine and pharmaceutical efforts, and coordinated efforts of the international community, give new hope to the Global effort to eliminate Ebola as a public health threat. Here we present a review of EBOV infection in an effort to further educate medical and political communities on what the Ebolavirus disease entails, and what efforts are recommended to treat, isolate, and eventually eliminate it.",2014 Oct-Dec,"['Kalra, Sarathi', 'Kelkar, Dhanashree', 'Galwankar, Sagar C.', 'Papadimos, Thomas J.', 'Stawicki, Stanislaw P.', 'Arquilla, Bonnie', 'Hoey, Brian A.', 'Sharpe, Richard P.', 'Sabol, Donna', 'Jahre, Jeffrey A.']",J Glob Infect Dis,,,
,PMC,Acute respiratory distress syndrome and pneumothorax,http://dx.doi.org/10.3978/j.issn.2072-1439.2014.08.34,PMC4203978,,,"Acute respiratory distress syndrome (ARDS) can occur during the treatment of several diseases and in several interventional procedures as a complication. It is a difficult situation to handle and special care should be applied to the patients. Mechanical ventilation is used for these patients and several parameters are changed constantly until compliance is achieved. However, a complication that is observed during the application of positive airway pressure is pneumothorax. In our current work we will present definition and causes of pneumothorax in the setting of intensive care unit (ICU). We will identify differences and similarities of this situation and present treatment options.",,"['Terzi, Eirini', 'Zarogoulidis, Konstantinos', 'Kougioumtzi, Ioanna', 'Dryllis, Georgios', 'Kioumis, Ioannis', 'Pitsiou, Georgia', 'Machairiotis, Nikolaos', 'Katsikogiannis, Nikolaos', 'Lampaki, Sofia', 'Papaiwannou, Antonis', 'Tsiouda, Theodora', 'Madesis, Athanasios', 'Karaiskos, Theodoros', 'Zaric, Bojan', 'Branislav, Perin', 'Zarogoulidis, Paul']",,,,
,PMC,Virus-Specific Memory CD8 T Cells Provide Substantial Protection from Lethal Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/JVI.01505-14,PMC4178831,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) caused an acute human respiratory illness with high morbidity and mortality in 2002-2003. Several studies have demonstrated the role of neutralizing antibodies induced by the spike (S) glycoprotein in protecting susceptible hosts from lethal infection. However, the anti-SARS-CoV antibody response is short-lived in patients who have recovered from SARS, making it critical to develop additional vaccine strategies. SARS-CoV-specific memory CD8 T cells persisted for up to 6 years after SARS-CoV infection, a time at which memory B cells and antivirus antibodies were undetectable in individuals who had recovered from SARS. In this study, we assessed the ability of virus-specific memory CD8 T cells to mediate protection against infection in the absence of SARS-CoV-specific memory CD4 T or B cells. We demonstrate that memory CD8 T cells specific for a single immunodominant epitope (S436 or S525) substantially protected 8- to 10-month-old mice from lethal SARS-CoV infection. Intravenous immunization with peptide-loaded dendritic cells (DCs) followed by intranasal boosting with recombinant vaccinia virus (rVV) encoding S436 or S525 resulted in accumulation of virus-specific memory CD8 T cells in bronchoalveolar lavage fluid (BAL), lungs, and spleen. Upon challenge with a lethal dose of SARS-CoV, virus-specific memory CD8 T cells efficiently produced multiple effector cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin 2 [IL-2]) and cytolytic molecules (granzyme B) and reduced lung viral loads. Overall, our results show that SARS-CoV-specific memory CD8 T cells protect susceptible hosts from lethal SARS-CoV infection, but they also suggest that SARS-CoV-specific CD4 T cell and antibody responses are necessary for complete protection. IMPORTANCE Virus-specific CD8 T cells are required for pathogen clearance following primary SARS-CoV infection. However, the role of SARS-CoV-specific memory CD8 T cells in mediating protection after SARS-CoV challenge has not been previously investigated. In this study, using a prime-boost immunization approach, we showed that virus-specific CD8 T cells protect susceptible 8- to 10-month-old mice from lethal SARS-CoV challenge. Thus, future vaccines against emerging coronaviruses should emphasize the generation of a memory CD8 T cell response for optimal protection.",,"['Channappanavar, Rudragouda', 'Fett, Craig', 'Zhao, Jincun', 'Meyerholz, David K.', 'Perlman, Stanley']",,,,
,PMC,Rational Design of Human Metapneumovirus Live Attenuated Vaccine Candidates by Inhibiting Viral mRNA Cap Methyltransferase,http://dx.doi.org/10.1128/JVI.00876-14,PMC4178811,,,"The paramyxoviruses human respiratory syncytial virus (hRSV), human metapneumovirus (hMPV), and human parainfluenza virus type 3 (hPIV3) are responsible for the majority of pediatric respiratory diseases and inflict significant economic loss, health care costs, and emotional burdens. Despite major efforts, there are no vaccines available for these viruses. The conserved region VI (CR VI) of the large (L) polymerase proteins of paramyxoviruses catalyzes methyltransferase (MTase) activities that typically methylate viral mRNAs at positions guanine N-7 (G-N-7) and ribose 2′-O. In this study, we generated a panel of recombinant hMPVs carrying mutations in the S-adenosylmethionine (SAM) binding site in CR VI of L protein. These recombinant viruses were specifically defective in ribose 2′-O methylation but not G-N-7 methylation and were genetically stable and highly attenuated in cell culture and viral replication in the upper and lower respiratory tracts of cotton rats. Importantly, vaccination of cotton rats with these recombinant hMPVs (rhMPVs) with defective MTases triggered a high level of neutralizing antibody, and the rats were completely protected from challenge with wild-type rhMPV. Collectively, our results indicate that (i) amino acid residues in the SAM binding site in the hMPV L protein are essential for 2′-O methylation and (ii) inhibition of mRNA cap MTase can serve as a novel target to rationally design live attenuated vaccines for hMPV and perhaps other paramyxoviruses, such as hRSV and hPIV3. IMPORTANCE Human paramyxoviruses, including hRSV, hMPV, and hPIV3, cause the majority of acute upper and lower respiratory tract infections in humans, particularly in infants, children, the elderly, and immunocompromised individuals. Currently, there is no licensed vaccine available. A formalin-inactivated vaccine is not suitable for these viruses because it causes enhanced lung damage upon reinfection with the same virus. A live attenuated vaccine is the most promising vaccine strategy for human paramyxoviruses. However, it remains a challenge to identify an attenuated virus strain that has an optimal balance between attenuation and immunogenicity. Using reverse genetics, we generated a panel of recombinant hMPVs that were specifically defective in ribose 2′-O methyltransferase (MTase) but not G-N-7 MTase. These MTase-defective hMPVs were genetically stable and sufficiently attenuated but retained high immunogenicity. This work highlights a critical role of 2′-O MTase in paramyxovirus replication and pathogenesis and a new avenue for the development of safe and efficacious live attenuated vaccines for hMPV and other human paramyxoviruses.",,"['Zhang, Yu', 'Wei, Yongwei', 'Zhang, Xiaodong', 'Cai, Hui', 'Niewiesk, Stefan', 'Li, Jianrong']",,,,
,PMC,Rooting the Phylogenetic Tree of Middle East Respiratory Syndrome Coronavirus by Characterization of a Conspecific Virus from an African Bat,http://dx.doi.org/10.1128/JVI.01498-14,PMC4178802,,,"The emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes lethal respiratory infections mainly on the Arabian Peninsula. The evolutionary origins of MERS-CoV are unknown. We determined the full genome sequence of a CoV directly from fecal material obtained from a South African Neoromicia capensis bat (NeoCoV). NeoCoV shared essential details of genome architecture with MERS-CoV. Eighty-five percent of the NeoCoV genome was identical to MERS-CoV at the nucleotide level. Based on taxonomic criteria, NeoCoV and MERS-CoV belonged to one viral species. The presence of a genetically divergent S1 subunit within the NeoCoV spike gene indicated that intraspike recombination events may have been involved in the emergence of MERS-CoV. NeoCoV constitutes a sister taxon of MERS-CoV, placing the MERS-CoV root between a recently described virus from African camels and all other viruses. This suggests a higher level of viral diversity in camels than in humans. Together with serologic evidence for widespread MERS-CoV infection in camelids sampled up to 20 years ago in Africa and the Arabian Peninsula, the genetic data indicate that camels act as sources of virus for humans rather than vice versa. The majority of camels on the Arabian Peninsula is imported from the Greater Horn of Africa, where several Neoromicia species occur. The acquisition of MERS-CoV by camels from bats might have taken place in sub-Saharan Africa. Camelids may represent mixing vessels for MERS-CoV and other mammalian CoVs. IMPORTANCE It is unclear how, when, and where the highly pathogenic MERS-CoV emerged. We characterized the full genome of an African bat virus closely related to MERS-CoV and show that human, camel, and bat viruses belong to the same viral species. The bat virus roots the phylogenetic tree of MERS-CoV, providing evidence for an evolution of MERS-CoV in camels that preceded that in humans. The revised tree suggests that humans are infected by camels rather than vice versa. Although MERS-CoV cases occur mainly on the Arabian Peninsula, the data from this study together with serologic and molecular investigations of African camels indicate that the initial host switch from bats may have taken place in Africa. The emergence of MERS-CoV likely involved exchanges of genetic elements between different viral ancestors. These exchanges may have taken place either in bat ancestors or in camels acting as mixing vessels for viruses from different hosts.",,"['Corman, Victor Max', 'Ithete, Ndapewa Laudika', 'Richards, Leigh Rosanne', 'Schoeman, M. Corrie', 'Preiser, Wolfgang', 'Drosten, Christian', 'Drexler, Jan Felix']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.02244-14,PMC4178800,,,,,,,,,
,PMC,Short Self-Interacting N-Terminal Region of Rubella Virus Capsid Protein Is Essential for Cooperative Actions of Capsid and Nonstructural p150 Proteins,http://dx.doi.org/10.1128/JVI.01758-14,PMC4178788,,,"Nucleocapsid formation is a primary function of the rubella virus capsid protein, which also promotes viral RNA synthesis via an unknown mechanism. The present study demonstrates that in infected cells, the capsid protein is associated with the nonstructural p150 protein via the short self-interacting N-terminal region of the capsid protein. Mutational analyses indicated that hydrophobic amino acids in this N-terminal region are essential for its N-terminal self-interaction, which is critical for the capsid-p150 association. An analysis based on a subgenomic replicon system demonstrated that the self-interacting N-terminal region of the capsid protein plays a key role in promoting viral gene expression. Analyses using a virus-like particle (VLP) system also showed that the self-interacting N-terminal region of the capsid protein is not essential for VLP production but is critical for VLP infectivity. These results demonstrate that the close cooperative actions of the capsid protein and p150 require the short self-interacting N-terminal region of the capsid protein during the life cycle of the rubella virus. IMPORTANCE The capsid protein of rubella virus promotes viral RNA replication via an unknown mechanism. This protein interacts with the nonstructural protein p150, but the importance of this interaction is unclear. In this study, we demonstrate that the short N-terminal region of the capsid protein forms a homo-oligomer that is critical for the capsid-p150 interaction. These interactions are required for the viral-gene-expression-promoting activity of the capsid protein, allowing efficient viral growth. These findings provide information about the mechanisms underlying the regulation of rubella virus RNA replication via the cooperative actions of the capsid protein and p150.",,"['Sakata, Masafumi', 'Otsuki, Noriyuki', 'Okamoto, Kiyoko', 'Anraku, Masaki', 'Nagai, Misato', 'Takeda, Makoto', 'Mori, Yoshio']",,,,
,PMC,"Histone Deacetylase 6 Inhibits Influenza A Virus Release by Downregulating the Trafficking of Viral Components to the Plasma Membrane via Its Substrate, Acetylated Microtubules",http://dx.doi.org/10.1128/JVI.00727-14,PMC4178787,,,"Mammalian cells produce many proteins, such as IFITM3, ISG15, MxA, and viperin, that inhibit influenza A virus (IAV) infection. Here, we show that a new class of host protein, histone deacetylase 6 (HDAC6), inhibits IAV infection. We found that HDAC6-overexpressing cells release about 3-fold less IAV progeny, whereas HDAC6-depleted cells release about 6-fold more IAV progeny. The deacetylase activity of HDAC6 played a role in its anti-IAV function as tubacin, a specific small-molecule inhibitor of HDAC6, increased the release of IAV progeny in a dose-dependent manner. Further, as visualized by electron microscopy, tubacin-treated cells showed an increase in IAV budding at the plasma membrane, the site of IAV assembly. Tubacin is a domain-specific inhibitor and binds to one of the two HDAC6 catalytic domains possessing tubulin deacetylase activity. This indicated the potential involvement of acetylated microtubules in the trafficking of viral components to the plasma membrane. Indeed, as quantified by flow cytometry, there was about a 2.0- to 2.5-fold increase and about a 2.0-fold decrease in the amount of viral envelope protein hemagglutinin present on the plasma membrane of tubacin-treated/HDAC6-depleted and HDAC6-overexpressing cells, respectively. In addition, the viral ribonucleoprotein complex was colocalized with acetylated microtubule filaments, and viral nucleoprotein coimmunoprecipitated with acetylated tubulin. Together, our findings indicate that HDAC6 is an anti-IAV host factor and exerts its anti-IAV function by negatively regulating the trafficking of viral components to the host cell plasma membrane via its substrate, acetylated microtubules. IMPORTANCE Host cells produce many proteins that have the natural ability to restrict influenza virus infection. Here, we discovered that another host protein, histone deacetylase 6 (HDAC6), inhibits influenza virus infection. We demonstrate that HDAC6 exerts its anti-influenza virus function by negatively regulating the trafficking of viral components to the site of influenza virus assembly via its substrate, acetylated microtubules. HDAC6 is a multisubstrate enzyme and regulates multiple cellular pathways, including the ones leading to various cancers, neurodegenerative diseases, and inflammatory disorders. Therefore, several drugs targeting HDAC6 are under clinical development for the treatment of a wide range of diseases. Influenza virus continues to be a major global public health problem due to regular emergence of drug-resistant and novel influenza virus strains in humans. As an alternative antiviral strategy, HDAC6 modulators could be employed to stimulate the anti-influenza virus potential of endogenous HDAC6 to inhibit influenza virus infection.",,"['Husain, Matloob', 'Cheung, Chen-Yi']",,,,
,PMC,"Coronaviruses Resistant to a 3C-Like Protease Inhibitor Are Attenuated for Replication and Pathogenesis, Revealing a Low Genetic Barrier but High Fitness Cost of Resistance",http://dx.doi.org/10.1128/JVI.01528-14,PMC4178758,,,"Viral protease inhibitors are remarkably effective at blocking the replication of viruses such as human immunodeficiency virus and hepatitis C virus, but they inevitably lead to the selection of inhibitor-resistant mutants, which may contribute to ongoing disease. Protease inhibitors blocking the replication of coronavirus (CoV), including the causative agents of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), provide a promising foundation for the development of anticoronaviral therapeutics. However, the selection and consequences of inhibitor-resistant CoVs are unknown. In this study, we exploited the model coronavirus, mouse hepatitis virus (MHV), to investigate the genotype and phenotype of MHV quasispecies selected for resistance to a broad-spectrum CoV 3C-like protease (3CLpro) inhibitor. Clonal sequencing identified single or double mutations within the 3CLpro coding sequence of inhibitor-resistant virus. Using reverse genetics to generate isogenic viruses with mutant 3CLpros, we found that viruses encoding double-mutant 3CLpros are fully resistant to the inhibitor and exhibit a significant delay in proteolytic processing of the viral replicase polyprotein. The inhibitor-resistant viruses also exhibited postponed and reduced production of infectious virus particles. Biochemical analysis verified double-mutant 3CLpro enzyme as impaired for protease activity and exhibiting reduced sensitivity to the inhibitor and revealed a delayed kinetics of inhibitor hydrolysis and activity restoration. Furthermore, the inhibitor-resistant virus was shown to be highly attenuated in mice. Our study provides the first insight into the pathogenicity and mechanism of 3CLpro inhibitor-resistant CoV mutants, revealing a low genetic barrier but high fitness cost of resistance. IMPORTANCE RNA viruses are infamous for their ability to evolve in response to selective pressure, such as the presence of antiviral drugs. For coronaviruses such as the causative agent of Middle East respiratory syndrome (MERS), protease inhibitors have been developed and shown to block virus replication, but the consequences of selection of inhibitor-resistant mutants have not been studied. Here, we report the low genetic barrier and relatively high deleterious consequences of CoV resistance to a 3CLpro protease inhibitor in a coronavirus model system, mouse hepatitis virus (MHV). We found that although mutations that confer resistance arise quickly, the resistant viruses replicate slowly and do not cause lethal disease in mice. Overall, our study provides the first analysis of the low barrier but high cost of resistance to a CoV 3CLpro inhibitor, which will facilitate the further development of protease inhibitors as anti-coronavirus therapeutics.",,"['Deng, Xufang', 'StJohn, Sarah E.', 'Osswald, Heather L.', ""O'Brien, Amornrat"", 'Banach, Bridget S.', 'Sleeman, Katrina', 'Ghosh, Arun K.', 'Mesecar, Andrew D.', 'Baker, Susan C.']",,,,
,PMC,DESC1 and MSPL Activate Influenza A Viruses and Emerging Coronaviruses for Host Cell Entry,http://dx.doi.org/10.1128/JVI.01427-14,PMC4178745,,,"The type II transmembrane serine protease (TTSP) TMPRSS2 cleaves and activates the influenza virus and coronavirus surface proteins. Expression of TMPRSS2 is essential for the spread and pathogenesis of H1N1 influenza viruses in mice. In contrast, H3N2 viruses are less dependent on TMPRSS2 for viral amplification, suggesting that these viruses might employ other TTSPs for their activation. Here, we analyzed TTSPs, reported to be expressed in the respiratory system, for the ability to activate influenza viruses and coronaviruses. We found that MSPL and, to a lesser degree, DESC1 are expressed in human lung tissue and cleave and activate the spike proteins of the Middle East respiratory syndrome and severe acute respiratory syndrome coronaviruses for cell-cell and virus-cell fusion. In addition, we show that these proteases support the spread of all influenza virus subtypes previously pandemic in humans. In sum, we identified two host cell proteases that could promote the amplification of influenza viruses and emerging coronaviruses in humans and might constitute targets for antiviral intervention. IMPORTANCE Activation of influenza viruses by host cell proteases is essential for viral infectivity and the enzymes responsible are potential targets for antiviral intervention. The present study demonstrates that two cellular serine proteases, DESC1 and MSPL, activate influenza viruses and emerging coronaviruses in cell culture and, because of their expression in human lung tissue, might promote viral spread in the infected host. Antiviral strategies aiming to prevent viral activation might thus need to encompass inhibitors targeting MSPL and DESC1.",,"['Zmora, Pawel', 'Blazejewska, Paulina', 'Moldenhauer, Anna-Sophie', 'Welsch, Kathrin', 'Nehlmeier, Inga', 'Wu, Qingyu', 'Schneider, Heike', 'Pöhlmann, Stefan', 'Bertram, Stephanie']",,,,
,PMC,Hepatitis E Virus Inhibits Type I Interferon Induction by ORF1 Products,http://dx.doi.org/10.1128/JVI.01935-14,PMC4178743,,,"Hepatitis E virus (HEV) causes both endemic and epidemic human hepatitis by fecal-oral transmission in many parts of the world. Zoonotic transmission of HEV from animals to humans has been reported. Due to the lack of an efficient cell culture system, the molecular mechanisms of HEV infection remain largely unknown. In this study, we found that HEV replication in hepatoma cells inhibited poly(I·C)-induced beta interferon (IFN-β) expression and that the HEV open reading frame 1 (ORF1) product was responsible for this inhibition. Two domains, X and the papain-like cysteine protease domain (PCP), of HEV ORF1 were identified as the putative IFN antagonists. When overexpressed in HEK293T cells, the X domain (or macro domain) inhibited poly(I·C)-induced phosphorylation of interferon regulatory factor 3 (IRF-3), which is the key transcription factor for IFN induction. The PCP domain was shown to have deubiquitinase activity for both RIG-I and TBK-1, whose ubiquitination is a key step in their activation in poly(I·C)-induced IFN induction. Furthermore, replication of a HEV replicon containing green fluorescent protein (GFP) (E2-GFP) in hepatoma cells led to impaired phosphorylation of IRF-3 and reduced ubiquitination of RIG-I and TBK-1, which confirmed our observations of X and PCP inhibitory effects in HEK293T cells. Altogether, our study identified the IFN antagonists within the HEV ORF1 polyprotein and expanded our understanding of the functions of several of the HEV ORF1 products, as well as the mechanisms of HEV pathogenesis. IMPORTANCE Type I interferons (IFNs) are important components of innate immunity and play a crucial role against viral infection. They also serve as key regulators to evoke an adaptive immune response. Virus infection can induce the synthesis of interferons; however, viruses have evolved many strategies to antagonize the induction of interferons. There is little knowledge about how hepatitis E virus (HEV) inhibits induction of host IFNs, though the viral genome was sequenced more than 2 decades ago. This is the first report of identification of the potential IFN antagonists encoded by HEV. By screening all the domains in the open reading frame 1 (ORF1) polyprotein, we identified two IFN antagonists and performed further research to determine how and at which step in the IFN induction pathway they antagonize host IFN induction. Our work provides valuable information about HEV-cell interaction and pathogenesis.",,"['Nan, Yuchen', 'Yu, Ying', 'Ma, Zexu', 'Khattar, Sunil K.', 'Fredericksen, Brenda', 'Zhang, Yan-Jin']",,,,
,PMC,Inhibition of the Human Respiratory Syncytial Virus Small Hydrophobic Protein and Structural Variations in a Bicelle Environment,http://dx.doi.org/10.1128/JVI.00839-14,PMC4178740,,,"The small hydrophobic (SH) protein is a 64-amino-acid polypeptide encoded by the human respiratory syncytial virus (hRSV). SH protein has a single α-helical transmembrane (TM) domain that forms pentameric ion channels. Herein, we report the first inhibitor of the SH protein channel, pyronin B, and we have mapped its binding site to a conserved surface of the RSV SH pentamer, at the C-terminal end of the transmembrane domain. The validity of the SH protein structural model used has been confirmed by using a bicellar membrane-mimicking environment. However, in bicelles the α-helical stretch of the TM domain extends up to His-51, and by comparison with previous models both His-22 and His-51 adopt an interhelical/lumenal orientation relative to the channel pore. Neither His residue was found to be essential for channel activity although His-51 protonation reduced channel activity at low pH, with His-22 adopting a more structural role. The latter results are in contrast with previous patch clamp data showing channel activation at low pH, which could not be reproduced in the present work. Overall, these results establish a solid ground for future drug development targeting this important viroporin. IMPORTANCE The human respiratory syncytial virus (hRSV) is responsible for 64 million reported cases of infection and 160,000 deaths each year. Lack of adequate antivirals fuels the search for new targets for treatment. The small hydrophobic (SH) protein is a 64-amino-acid polypeptide encoded by hRSV and other paramyxoviruses, and its absence leads to viral attenuation in vivo and early apoptosis in infected cells. SH protein forms pentameric ion channels that may constitute novel drug targets, but no inhibitor for this channel activity has been reported so far. A small-molecule inhibitor, pyronin B, can reduce SH channel activity, and its likely binding site on the SH protein channel has been identified. Black lipid membrane (BLM) experiments confirm that protonation of both histidine residues reduces stability and channel activity. These results contrast with previous patch clamp data that showed low-pH activation, which we have not been able to reproduce.",,"['Li, Yan', 'To, Janet', 'Verdià-Baguena, Carmina', 'Dossena, Silvia', 'Surya, Wahyu', 'Huang, Mei', 'Paulmichl, Markus', 'Liu, Ding Xiang', 'Aguilella, Vicente M.', 'Torres, Jaume']",,,,
,PMC,A Chimeric Virus-Mouse Model System for Evaluating the Function and Inhibition of Papain-Like Proteases of Emerging Coronaviruses,http://dx.doi.org/10.1128/JVI.01749-14,PMC4178736,,,"To combat emerging coronaviruses, developing safe and efficient platforms to evaluate viral protease activities and the efficacy of protease inhibitors is a high priority. Here, we exploit a biosafety level 2 (BSL-2) chimeric Sindbis virus system to evaluate protease activities and the efficacy of inhibitors directed against the papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus (SARS-CoV), a biosafety level 3 (BSL-3) pathogen. We engineered Sindbis virus to coexpress PLpro and a substrate, murine interferon-stimulated gene 15 (ISG15), and found that PLpro mediates removal of ISG15 (deISGylation) from cellular proteins. Mutation of the catalytic cysteine residue of PLpro or addition of a PLpro inhibitor blocked deISGylation in virus-infected cells. Thus, deISGylation is a marker of PLpro activity. Infection of alpha/beta interferon receptor knockout (IFNAR(−/−)) mice with these chimeric viruses revealed that PLpro deISGylation activity removed ISG15-mediated protection during viral infection. Importantly, administration of a PLpro inhibitor protected these mice from lethal infection, demonstrating the efficacy of a coronavirus protease inhibitor in a mouse model. However, this PLpro inhibitor was not sufficient to protect the mice from lethal infection with SARS-CoV MA15, suggesting that further optimization of the delivery and stability of PLpro inhibitors is needed. We extended the chimeric-virus platform to evaluate the papain-like protease/deISGylating activity of Middle East respiratory syndrome coronavirus (MERS-CoV) to provide a small-animal model to evaluate PLpro inhibitors of this recently emerged pathogen. This platform has the potential to be universally adaptable to other viral and cellular enzymes that have deISGylating activities. IMPORTANCE Evaluating viral protease inhibitors in a small-animal model is a critical step in the path toward antiviral drug development. We modified a biosafety level 2 chimeric virus system to facilitate evaluation of inhibitors directed against highly pathogenic coronaviruses. We used this system to demonstrate the in vivo efficacy of an inhibitor of the papain-like protease of severe acute respiratory syndrome coronavirus. Furthermore, we demonstrate that the chimeric-virus system can be adapted to study the proteases of emerging human pathogens, such as Middle East respiratory syndrome coronavirus. This system provides an important tool to rapidly assess the efficacy of protease inhibitors targeting existing and emerging human pathogens, as well as other enzymes capable of removing ISG15 from cellular proteins.",,"['Deng, Xufang', 'Agnihothram, Sudhakar', 'Mielech, Anna M.', 'Nichols, Daniel B.', 'Wilson, Michael W.', 'StJohn, Sarah E.', 'Larsen, Scott D.', 'Mesecar, Andrew D.', 'Lenschow, Deborah J.', 'Baric, Ralph S.', 'Baker, Susan C.']",,,,
,PMC,Mutagenesis of the Catalytic and Cleavage Site Residues of the Hypovirus Papain-Like Proteases p29 and p48 Reveals Alternative Processing and Contributions to Optimal Viral RNA Accumulation,http://dx.doi.org/10.1128/JVI.01489-14,PMC4178723,,,"The positive-stranded RNA genome of the prototypic virulence-attenuating hypovirus CHV-1/EP713 contains two open reading frames (ORF), each encoding an autocatalytic papain-like leader protease. Protease p29, derived from the N-terminal portion of ORF A, functions as a suppressor of RNA silencing, while protease p48, derived from the N-terminal portion of ORF B, is required for viral RNA replication. The catalytic and cleavage site residues required for autoproteolytic processing have been functionally mapped in vitro for both proteases but not confirmed in the infected fungal host. We report here the mutagenesis of the CHV-1/EP713 infectious cDNA clone to define the requirements for p29 and p48 cleavage and the role of autoproteolysis in the context of hypovirus replication. Mutation of the catalytic cysteine and histidine residues for either p29 or p48 was tolerated but reduced viral RNA accumulation to ca. 20 to 50% of the wild-type level. Mutation of the p29 catalytic residues caused an accumulation of unprocessed ORF A product p69. Surprisingly, the release of p48 from the ORF B-encoded polyprotein was not prevented by mutation of the p48 catalytic and cleavage site residues and was independent of p29. The results show that, while dispensable for hypovirus replication, the autocatalytic processing of the leader proteases p29 and p48 contributes to optimal virus RNA accumulation. The role of the predicted catalytic residues in autoproteolytic processing of p29 was confirmed in the infected host, while p48 was found to also undergo alternative processing independent of the encoded papain-like protease activities. IMPORTANCE Hypoviruses are positive-strand RNA mycoviruses that attenuate virulence of their pathogenic fungal hosts. The prototypic hypovirus CHV-1/EP713, which infects the chestnut bight fungus Cryphonetria parasitica, encodes two papain-like autocatalytic leader proteases, p29 and p48, that also have important functions in suppressing the RNA silencing antiviral defense response and in viral RNA replication, respectively. The mutational analyses of the CHV-1/EP713 infectious cDNA clone, reported here, define the requirements for p29 and p48 cleavage and the functional importance of autoproteolysis in the context of hypovirus replication and exposed an alternative p48 processing pathway independent of the encoded papain-like protease activities. These findings provide additional insights into hypovirus gene expression, replication, and evolution and inform ongoing efforts to engineer hypoviruses for interrogating and modulating fungal virulence.",,"['Jensen, Kenneth S.', 'Nuss, Donald L.']",,,,
,PMC,Facts and ideas from anywhere,,PMC4255875,,,,,,,,,
,PMC,Activating Receptor NKG2D Targets RAE-1-Expressing Allogeneic Neural Precursor Cells in a Viral Model of Multiple Sclerosis,http://dx.doi.org/10.1002/stem.1760,PMC4165828,,,"Transplantation of major histocompatibility complex (MHC)-mismatched mouse neural precursor cells (NPCs) into mice persistently infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in rapid rejection that is mediated, in part, by T cells. However, the contribution of the innate immune response to allograft rejection in a model of viral-induced neurological disease has not been well defined. Herein, we demonstrate that the natural killer (NK) cell-expressing activating receptor NKG2D participates in transplanted allogeneic NPC rejection in mice persistently infected with JHMV. Cultured NPCs derived from C57BL/6 (H-2(b)) mice express the NKG2D ligand retinoic acid early precursor transcript (RAE)-1 but expression was dramatically reduced upon differentiation into either glia or neurons. RAE-1(+) NPCs were susceptible to NK cell-mediated killing whereas RAE-1(-) cells were resistant to lysis. Transplantation of C57BL/6-derived NPCs into JHMV-infected BALB/c (H-2(d)) mice resulted in infiltration of NKG2D(+)CD49b(+) NK cells and treatment with blocking antibody specific for NKG2D increased survival of allogeneic NPCs. Further, transplantation of differentiated RAE-1(-) allogeneic NPCs into JHMV-infected BALB/c mice resulted in enhanced survival, highlighting a role for the NKG2D:RAE-1 signaling axis in allograft rejection. We also demonstrate that transplantation of allogeneic NPCs into JHMV-infected mice resulted in infection of the transplanted cells suggesting that these cells may be targets for infection. Viral infection of cultured cells increased RAE-1 expression, resulting in enhanced NK cell-mediated killing through NKG2D recognition. Collectively, these results show that in a viral-induced demyelination model, NK cells contribute to rejection of allogeneic NPCs through an NKG2D signaling pathway.",,"['Weinger, Jason G.', 'Plaisted, Warren C.', 'Maciejewski, Sonia M.', 'Lanier, Lewis L.', 'Walsh, Craig M.', 'Lane, Thomas E.']",,,,
,PMC,"Circulating mannan-binding lectin, M-, L-, H-ficolin, and collectin-liver-1 levels in patients with acute liver failure",http://dx.doi.org/10.1111/liv.12682,PMC4329085,,,"BACKGROUND: The complement system is activated in liver diseases including acute liver failure (ALF); however, the role of the lectin pathway of complement has scarcely been investigated in ALF. The pathway is initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL), M-, L- and H-ficolin and collectin-liver-1 (CL-L1), which are predominantly synthesised in the liver. AIM: We aimed to study lectin levels in ALF patients and associations with clinical outcome. METHODS: Serum samples from 75 patients enrolled by the U.S. ALF Study Group were collected on days 1 and 3. We included 75 healthy blood donors and 20 cirrhosis patients as controls. Analyses were performed using sandwich-type immunoassays (ELISA, TRIFMA). RESULTS: At day 1, the MBL level in ALF patients was 40% lower compared with healthy controls ((median(interquartile range) 0.72 μg/ml(0.91) vs. 1.15(1.92)(p=0.02)), and increased significantly by day 3 (0.83 μg/ml(0.94)(p=0.01)). The M-ficolin level was 60% lower (0.54 μg/ml(0.50) vs. 1.48(1.01)(p<0.0001)). The CL-L1 level at day 1 was slightly higher compared with healthy controls (3.20 μg/ml(2.37) vs. 2.64(0.72)(p=0.11)); this was significant at day 3 (3.35(1.84)(p=0.006)). H- and L-ficolin levels were similar to healthy controls. Spontaneous ALF survivors had higher levels of MBL at day 1 (0.96 μg/ml(1.15) vs. 0.60(0.60)(p=0.02)) and lower levels of L-ficolin by day 3 compared with patients who died or were transplanted (1.61 μg/ml(1.19) vs. 2.17(2.19)(p=0.02)). CONCLUSION: We observed significant dynamics in lectin levels in ALF patients, which may suggest they play a role in ALF pathogenesis. High MBL and low L-ficolin levels are associated with survival.",,"['Laursen, Tea Lund', 'Sandahl, Thomas Damgaard', 'Støy, Sidsel', 'Schiødt, Frank Vinholt', 'Lee, William M.', 'Vilstrup, Hendrik', 'Thiel, Steffen', 'Grønbæk, Henning', None]",,,,
,PMC,"Coronavirus non-structural protein 16: Evasion, attenuation, and possible treatments",http://dx.doi.org/10.1016/j.virusres.2014.09.009,PMC4260984,,,"The recent emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV), nearly a decade after the Severe Acute Respiratory Syndrome (SARS) CoV, highlights the importance of understanding and developing therapeutic treatment for current and emergent CoVs. This manuscript explores the role of NSP16, a 2′O-methyl-transferase (2′O-MTase), in CoV infection and the host immune response. The review highlights conserved motifs, required interaction partners, as well as the attenuation of NSP16 mutants, and restoration of these mutants in specific immune knockouts. Importantly, the work also identifies a number of approaches to exploit this understanding for therapeutic treatment and the data clearly illustrate the importance of NSP16 2′O-MTase activity for CoV infection and pathogenesis.",,"['Menachery, Vineet D.', 'Debbink, Kari', 'Baric, Ralph S.']",,,,
,PMC,Croup,,PMC4178284,,,"INTRODUCTION: Croup is characterised by the abrupt onset, most commonly at night, of a barking cough, inspiratory stridor, hoarseness, and respiratory distress due to upper airway obstruction. It leads to signs of upper airway obstruction, and must be differentiated from acute epiglottitis, bacterial tracheitis, or an inhaled foreign body. Croup affects about 3% of children per year, usually between the ages of 6 months and 3 years, and 75% of infections are caused by parainfluenza virus. Symptoms usually resolve within 48 hours, but severe upper airway obstruction can, rarely, lead to respiratory failure and arrest. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in children with mild croup and moderate to severe croup? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 19 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: corticosteroids (dexamethasone, intramuscular and oral), nebulised budesonide, oral prednisolone, heliox, humidification, and nebulised adrenaline (racemate and L-adrenaline [ephinephrine]).",,"Johnson, David Wyatt",,,,
,PMC,"Abstracts published at Infection Prevention 2014, Glasgow",http://dx.doi.org/10.1177/1757177414547832,PMC5074092,,,,,,,,,
,PMC,Sterile and Microbial-associated Intra-amniotic Inflammation in Preterm Prelabor Rupture of Membranes,http://dx.doi.org/10.3109/14767058.2014.958463,PMC5371030,,,"OBJECTIVE: The objectives of this study were to: 1) determine the amniotic fluid (AF) microbiology of patients with preterm prelabor rupture of membranes (PROM); and 2) examine the relationship between intra-amniotic inflammation with and without microorganisms (sterile inflammation) and adverse pregnancy outcomes in patients with preterm PROM. METHODS: AF samples obtained from 59 women with preterm PROM were analyzed using cultivation techniques (for aerobic and anaerobic bacteria as well as genital mycoplasmas) and with broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). AF concentration of interleukin-6 (IL-6) was determined using ELISA. Results of both tests were correlated with AF IL-6 concentrations, and the occurrence of adverse obstetrical/perinatal outcomes. RESULTS: 1) PCR/ESI-MS, AF culture, and the combination of these two tests, each identified microorganisms in 36% (21/59), 24% (14/59) and 41% (24/59) of women with preterm PROM, respectively; 2) the most frequent microorganisms found in the amniotic cavity were Sneathia species and Ureaplasma urealyticum; 3) the frequency of microbial-associated and sterile intra-amniotic inflammation was overall similar [ 29% (17/59)]: - however, the prevalence of each differed according to the gestational age when PROM occurred ; 4) the earlier the gestational age at preterm PROM, the higher the frequency of both microbial-associated and sterile intra-amniotic inflammation; 5) the intensity of the intra-amniotic inflammatory response against microorganisms is stronger when preterm PROM occurs early in pregnancy; and 6) the frequency of acute placental inflammation (histologic chorioamnionitis and/or funisitis) was significantly higher in patients with microbial-associated intra-amniotic inflammation than in those without intra-amniotic inflammation [93.3% (14/15) vs. 38% (6/16); p=0.001]. CONCLUSIONS: 1) The frequency of microorganisms in preterm PROM is 40% using both cultivation and PCR/ESI-MS; 2) PCR/ESI-MS identified microorganisms in the AF of 50% more women with preterm PROM than did AF culture; and 3) sterile intra-amniotic inflammation was present in 29% of these patients, and it was as or more common than microbial-associated intra-amniotic inflammation among those presenting after, but not before, 24 weeks of gestation.",,"['Romero, Roberto', 'Miranda, Jezid', 'Chaemsaithong, Piya', 'Chaiworapongsa, Tinnakorn', 'Kusanovic, Juan P.', 'Dong, Zhong', 'Ahmed, Ahmed I.', 'Shaman, Majid', 'Lannaman, Kia', 'Yoon, Bo Hyun', 'Hassan, Sonia S.', 'Kim, Chong J.', 'Korzeniewski, Steven J.', 'Yeo, Lami', 'Kim, Yeon Mee']",,,,
,PMC,Phosphatidylserine receptors: enhancers of enveloped virus entry and infection,http://dx.doi.org/10.1016/j.virol.2014.09.009,PMC4252826,,,"A variety of both RNA and DNA viruses envelop their capsids in a lipid bilayer. One of the more recently appreciated benefits this envelope is incorporation of phosphatidylserine (PtdSer). Surface exposure of PtdSer disguises viruses as apoptotic bodies; tricking cells into engulfing virions. This mechanism is termed apoptotic mimicry. Several PtdSer receptors have been identified to enhance virus entry and we have termed this group of proteins PtdSer-mediated virus entry enhancing receptors or PVEERs. These receptors enhance entry of a broad range of enveloped viruses. Internalization of virions by PVEERs provides a broad mechanism of entry with little investment by the virus itself and may allow some viruses to attach to cells, thereby making viral glycoprotein/cellular receptor interactions more probable. Alternatively, other viruses may rely entirely on PVEERs for internalization into endosomes. This review provides an overview of PtdSer receptors that serve as PVEERs and the biology behind virion/PVEER interaction.",,"['Moller-Tank, Sven', 'Maury, Wendy']",,,,
,PMC,Geographic variation in the eukaryotic virome of human diarrhea,http://dx.doi.org/10.1016/j.virol.2014.09.012,PMC4254309,,,"Little is known about the population of eukaryotic viruses in the human gut (“virome”) or the potential role it may play in disease. We used a metagenomic approach to define and compare the eukaryotic viromes in pediatric diarrhea cohorts from two locations (Melbourne and Northern Territory, Australia). We detected viruses known to cause diarrhea, non-pathogenic enteric viruses, viruses not associated with an enteric reservoir, viruses of plants, and novel viruses. Viromes from Northern Territory children contained more viral families per sample than viromes from Melbourne, which could be attributed largely to an increased number of sequences from the families Adenoviridae and Picornaviridae (genus enterovirus). qRT-PCR/PCR confirmed the increased prevalence of adenoviruses and enteroviruses. Testing of additional diarrhea cohorts by qRT-PCR/PCR demonstrated statistically different prevalences in different geographic sites. These findings raise the question of whether the virome plays a role in enteric diseases and conditions that vary with geography.",,"['Holtz, Lori R.', 'Cao, Song', 'Zhao, Guoyan', 'Bauer, Irma K.', 'Denno, Donna M.', 'Klein, Eileen J.', 'Antonio, Martin', 'Stine, O. Colin', 'Snelling, Thomas L.', 'Kirkwood, Carl D.', 'Wang, David']",,,,
,PMC,Toso regulates differentiation and activation of inflammatory dendritic cells during persistence-prone virus infection,http://dx.doi.org/10.1038/cdd.2014.138,PMC4262783,,,"During virus infection and autoimmune disease, inflammatory dendritic cells (iDCs) differentiate from blood monocytes and infiltrate infected tissue. Following acute infection with hepatotropic viruses, iDCs are essential for re-stimulating virus-specific CD8(+) T cells and therefore contribute to virus control. Here we used the lymphocytic choriomeningitis virus (LCMV) model system to identify novel signals, which influence the recruitment and activation of iDCs in the liver. We observed that intrinsic expression of Toso (Faim3, FcμR) influenced the differentiation and activation of iDCs in vivo and DCs in vitro. Lack of iDCs in Toso-deficient (Toso(–/–)) mice reduced CD8(+) T-cell function in the liver and resulted in virus persistence. Furthermore, Toso(–/–) DCs failed to induce autoimmune diabetes in the rat insulin promoter-glycoprotein (RIP-GP) autoimmune diabetes model. In conclusion, we found that Toso has an essential role in the differentiation and maturation of iDCs, a process that is required for the control of persistence-prone virus infection.",,"['Lang, P A', 'Meryk, A', 'Pandyra, A A', 'Brenner, D', 'Brüstle, A', 'Xu, H C', 'Merches, K', 'Lang, F', 'Khairnar, V', 'Sharma, P', 'Funkner, P', 'Recher, M', 'Shaabani, N', 'Duncan, G S', 'Duhan, V', 'Homey, B', 'Ohashi, P S', 'Häussinger, D', 'Knolle, P A', 'Honke, N', 'Mak, T W', 'Lang, K S']",,,,
,PMC,THE DUALITY OF FGL2 - SECRETED IMMUNE CHECKPOINT REGULATOR VERSUS MEMBRANE-ASSOCIATED PROCOAGULANT: THERAPEUTIC POTENTIAL AND IMPLICATIONS,http://dx.doi.org/10.3109/08830185.2014.956360,PMC5257246,,,"Fibrinogen-like protein 2 (Fgl2), a member of the fibrinogen family, can be expressed as a membrane-associated protein with coagulation activity or in a secreted form possessing unique immune suppressive functions. The biological importance of Fgl2 is evident within viral-induced fibrin depositing inflammatory diseases and malignancies and provides a compelling rationale for Fgl2 expression to not only be considered as a disease biomarker but also as a therapeutic target. This article will provide a comprehensive review of the currently known biological properties of Fgl2 and clarifies future scientific directives.",,"['Hu, Jiemiao', 'Yan, Jun', 'Rao, Ganesh', 'Latha, Khatri', 'Overwijk, Willem W.', 'Heimberger, Amy B', 'Li, Shulin']",,,,
,PMC,Complex N-Linked Glycans Serve as a Determinant for Exosome/Microvesicle Cargo Recruitment,http://dx.doi.org/10.1074/jbc.M114.606269,PMC4239607,,,"Exosomes, also known as microvesicles (EMVs), are nano-sized membranous particles secreted from nearly all mammalian cell types. These nanoparticles play critical roles in many physiological processes including cell-cell signaling, immune activation, and suppression and are associated with disease states such as tumor progression. The biological functions of EMVs are highly dependent on their protein composition, which can dictate pathogenicity. Although some mechanisms have been proposed for the regulation of EMV protein trafficking, little attention has been paid to N-linked glycosylation as a potential sorting signal. Previous work from our laboratory found a conserved glycan signature for EMVs, which differed from that of the parent cell membranes, suggesting a potential role for glycosylation in EMV biogenesis. In this study, we further explore the role of glycosylation in EMV protein trafficking. We identify EMV glycoproteins and demonstrate alteration of their recruitment as a function of their glycosylation status upon pharmacological manipulation. Furthermore, we show that genetic manipulation of the glycosylation levels of a specific EMV glycoprotein, EWI-2, directly impacts its recruitment as a function of N-linked glycan sites. Taken together, our data provide strong evidence that N-linked glycosylation directs glycoprotein sorting into EMVs.",,"['Liang, Yaxuan', 'Eng, William S.', 'Colquhoun, David R.', 'Dinglasan, Rhoel R.', 'Graham, David R.', 'Mahal, Lara K.']",,,,
,PMC,Evolution of a Search: The Use of Dynamic Twitter Searches During Superstorm Sandy,http://dx.doi.org/10.1371/currents.dis.de9415573fbf90ee2c585cd0b2314547,PMC4205228,25642372,CC BY,"Background: Twitter has emerged as a critical source of free and openly available information during emergency response operations, providing an unmatched level of on-the-ground situational awareness in real-time. Responders and survivors turn to Twitter to share information and resources within communities, conduct rumor control, and provide a “boots on the ground” understanding of the disaster. However, the ability to tune out background “noise” is essential to effectively utilizing Twitter to identify important and useful information during an emergency response. Methods: This article highlights a two-prong strategy in which the use of a Twitter list paired with subject specific Boolean searches provided increased situational awareness and early event detection during the United States Department of Health and Human Services (HHS), Office of the Assistant Secretary for Preparedness and Response (ASPR) response to Superstorm Sandy in 2012. To maximize the amount of relevant information that was retrieved, the Twitter list and Boolean searches were dynamic and responsive to real-time developments, evolving health threats, and the informational needs of decision-makers. Conclusion: The use of a Twitter list combined with Boolean searches led to enhanced situational awareness throughout the HHS response. The incorporation of a dynamic search strategy over the course of the HHS Sandy response, allowed for the ability to account for over-tweeted information, changes in event related conversation, and decreases in the return of relevant information.",2014 Sep 26,"['Harris Smith, Sara', 'Bennett, Kelly J.', 'Livinski, Alicia A.']",PLoS Curr,,,
,PMC,Platelet Count Mediates the Contribution of a Genetic Variant in LRRC16A to ARDS Risk,http://dx.doi.org/10.1378/chest.14-1246,PMC4347530,,,"BACKGROUND: Platelets are believed to be critical in pulmonary-origin ARDS as mediators of endothelial damage through their interactions with fibrinogen and multiple signal transduction pathways. A prior meta-analysis identified five loci for platelet count (PLT): BAD, LRRC16A, CD36, JMJD1C, and SLMO2. This study aims to validate the quantitative trait loci (QTLs) of PLT within BAD, LRRC16A, CD36, JMJD1C, and SLMO2 among critically ill patients and to investigate the associations of these QTLs with ARDS risk that may be mediated through PLT. METHODS: ARDS cases and at-risk control subjects were recruited from the intensive care unit of the Massachusetts General Hospital. Exome-wide genotyping data of 629 ARDS cases and 1,026 at-risk control subjects and genome-wide gene expression profiles of 18 at-risk control subjects were generated for analysis. RESULTS: Single-nucleotide polymorphism (SNP) rs7766874 within LRRC16A was a significant locus for PLT among at-risk control subjects (β = −13.00; 95% CI, −23.22 to −2.77; P = .013). This association was validated using LRRC16A gene expression data from at-risk control subjects (β = 77.03 per 1 SD increase of log(2)-transformed expression; 95% CI, 27.26-126.80; P = .005). Further, rs7766874 was associated with ARDS risk conditioned on PLT (OR = 0.68; 95% CI, 0.51-0.90; P = .007), interacting with PLT (OR = 1.15 per effect allele per 100 × 10(3)/μL of PLT; 95% CI, 1.03-1.30; P = .015), and mediated through PLT (indirect OR = 1.045; 95% CI, 1.007-1.085; P = .021). CONCLUSIONS: Our findings support the role of LRRC16A in platelet formation and suggest the importance of LRRC16A in ARDS pathophysiology by interacting with, and being mediated through, platelets.",,"['Wei, Yongyue', 'Wang, Zhaoxi', 'Su, Li', 'Chen, Feng', 'Tejera, Paula', 'Bajwa, Ednan K.', 'Wurfel, Mark M.', 'Lin, Xihong', 'Christiani, David C.']",,,,
,PMC,An Internet-Based Epidemiological Investigation of the Outbreak of H7N9 Avian Influenza A in China Since Early 2013,http://dx.doi.org/10.2196/jmir.3763,PMC4211021,25257217,CC BY,"BACKGROUND: In early 2013, a new type of avian influenza, H7N9, emerged in China. It quickly became an issue of great public concern and a widely discussed topic on the Internet. A considerable volume of relevant information was made publicly available on the Internet through various sources. OBJECTIVE: This study aimed to describe the outbreak of H7N9 in China based on data openly available on the Internet and to validate our investigation by comparing our findings with a well-conducted conventional field epidemiologic study. METHODS: We searched publicly accessible Internet data on the H7N9 outbreak primarily from government and major mass media websites in China up to February 10, 2014. Two researchers independently extracted, compared, and confirmed the information of each confirmed H7N9 case using a self-designed data extraction form. We summarized the epidemiological and clinical characteristics of confirmed H7N9 cases and compared them with those from the field study. RESULTS: According to our data updated until February 10, 2014, 334 confirmed H7N9 cases were identified. The median age was 58 years and 67.0% (219/327) were males. Cases were reported in 15 regions in China. Five family clusters were found. Of the 16.8% (56/334) of the cases with relevant data, 69.6% (39/56) reported a history of exposure to animals. Of the 1751 persons with a close contact with a confirmed case, 0.6% (11/1751) of them developed respiratory symptoms during the 7-day surveillance period. In the 97.9% (327/334) of the cases with relevant data, 21.7% (71/327) died, 20.8% (68/327) were discharged from a hospital, and 57.5% (188/327) were of uncertain status. We compared our findings before February 10, 2014 and those before December 1, 2013 with those from the conventional field study, which had the latter cutoff date of ours in data collection. Our study showed most epidemiological and clinical characteristics were similar to those in the field study, except for case fatality (71/327, 21.7% for our data before February 10; 45/138, 32.6% for our data before December 1; 47/139, 33.8% for the field study), time from illness onset to first medical care (4 days, 3 days, and 1 day), and time from illness onset to death (16.5 days, 17 days, and 21 days). CONCLUSIONS: Findings from our Internet-based investigation were similar to those from the conventional field study in most epidemiological and clinical aspects of the outbreak. Importantly, publicly available Internet data are open to any interested researchers and can thus greatly facilitate the investigation and control of such outbreaks. With improved efforts for Internet data provision, Internet-based investigation has a great potential to become a quick, economical, novel approach to investigating sudden issues of great public concern that involve a relatively small number of cases like this H7N9 outbreak.",2014 Sep 25,"['Mao, Chen', 'Wu, Xin-Yin', 'Fu, Xiao-Hong', 'Di, Meng-Yang', 'Yu, Yuan-Yuan', 'Yuan, Jin-Qiu', 'Yang, Zu-Yao', 'Tang, Jin-Ling']",J Med Internet Res,,,
,PMC,Long non-coding RNAs and control of gene expression in the immune system,http://dx.doi.org/10.1016/j.molmed.2014.09.002,PMC4252818,,,"All cells of the immune system rely on a highly integrated and dynamic gene expression program that is controlled by both transcriptional and post-transcriptional mechanisms. Recently, non-coding RNAs, including long non-coding RNAs (lncRNA), have emerged as important regulators of gene expression in diverse biological contexts. Long non-coding RNAs control gene expression in the nucleus by modulating transcription or via post-transcriptional mechanisms targeting the splicing, stability or translation of mRNAs. Our knowledge of lncRNA biogenesis, their cell-type specific expressions, and their versatile molecular functions are rapidly progressing in all areas of biology. Here we discuss these exciting new regulators and highlight an emerging paradigm of lncRNA-mediated control of gene expression in the immune system.",,"['Atianand, Maninjay K.', 'Fitzgerald, Katherine A.']",,,,
,PMC,Sterile Intra-amniotic Inflammation in Asymptomatic Patients with a Sonographic Short Cervix: Prevalence and Clinical Significance,http://dx.doi.org/10.3109/14767058.2014.954243,PMC4372495,,,"OBJECTIVE: To determine the frequency and clinical significance of sterile- and microbial-associated intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix. METHODS: Amniotic fluid (AF) samples obtained by transabdominal amniocentesis from 231 asymptomatic women with a sonographic short cervix [cervical length (CL) ≤25 mm] were analyzed using cultivation techniques (for aerobic and anaerobic as well as genital mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). The frequency and magnitude of intra-amniotic inflammation [defined as an AF interleukin (IL)-6 concentration ≥2.6 ng/mL], acute histologic placental inflammation, spontaneous preterm delivery, and the amniocentesis-to-delivery interval were examined according to the results of AF cultures, PCR/ESI-MS and AF IL-6 concentrations. RESULTS: Ten percent (24/231) of patients with a sonographic short cervix had sterile intra-amniotic inflammation (an elevated AF IL-6 concentration without evidence of microorganisms using cultivation and molecular methods). Sterile intra-amniotic inflammation was significantly more frequent than microbial-associated intra-amniotic inflammation [10.4% (24/231) vs. 2.2% (5/231); p<0.001]. Patients with sterile intra-amniotic inflammation had a significantly higher rate of spontaneous preterm delivery <34 weeks of gestation [70.8% (17/24) vs. 31.6% (55/174); p<0.001] and a significantly shorter amniocentesis-to-delivery interval than patients without intra-amniotic inflammation [median 35, (IQR: 10 – 70) vs. median 71, (IQR: 47 – 98) days, (p<0.0001)]. CONCLUSION: Sterile intra-amniotic inflammation is more common than microbial-associated intra-amniotic inflammation in asymptomatic women with a sonographic short cervix, and is associated with increased risk of spontaneous preterm delivery (<34 weeks). Further investigation is required to determine the causes of sterile intra-amniotic inflammation and the mechanisms whereby this condition is associated with a short cervix and spontaneous preterm delivery.",,"['Romero, Roberto', 'Miranda, Jezid', 'Chaiworapongsa, Tinnakorn', 'Chaemsaithong, Piya', 'Gotsch, Francesca', 'Dong, Zhong', 'Ahmed, Ahmed I.', 'Yoon, Bo Hyun', 'Hassan, Sonia S.', 'Kim, Chong J.', 'Korzeniewski, Steven J.', 'Yeo, Lami', 'Kim, Yeon Mee']",,,,
,PMC,"Beyond SNPs—genetics, genomics and other ‘omic approaches to ARDS",http://dx.doi.org/10.1016/j.ccm.2014.08.006,PMC5629971,,,"This article summarizes the contributions of high throughput genomic, proteomic, metabolomic, and gene expression investigations to our understanding of inherited or acquired risk for acute respiratory distress syndrome (ARDS). While not yet widely applied to a complex trait like ARDS, these techniques are now routinely employed to study a variety of disease states. Omic applications hold great promise for identifying novel factors that may contribute to ARDS pathophysiology or may be appropriate for further development as biomarkers or surrogates in clinical studies. Opportunities and challenges of different techniques are discussed, and examples of successful applications in non-ARDS fields are used to illustrate the potential utility of each technique.",,"Meyer, Nuala J.",,,,
,PMC,Predicting support for non-pharmaceutical interventions during infectious outbreaks: a four region analysis,http://dx.doi.org/10.1111/disa.12089,PMC4355939,,,"Non-pharmaceutical interventions (NPIs) are an important public health tool for responding to infectious disease outbreaks, including pandemics. However, little is known about the individual characteristics associated with support for NPIs, or whether they are consistent across regions. This study draws on survey data from four regions—Hong Kong, Singapore, Taiwan, and the United States—collected following the Severe Acute Respiratory Syndrome (SARS) outbreak of 2002–03, and employs regression techniques to estimate predictors of NPI support. It finds that characteristics associated with NPI support vary widely by region, possibly because of cultural variation and prior experience, and that minority groups tend to be less supportive of NPIs when arrest is the consequence of noncompliance. Prior experience of face-mask usage also results in increased support for future usage, as well as other NPIs. Policymakers should be attentive to local preferences and to the application of compulsory interventions. It is speculated here that some public health interventions may serve as ‘gateway’ exposures to future public health interventions.",,"['Pillemer, Francesca Matthews', 'Blendon, Robert J.', 'Zaslavsky, Alan M.', 'Lee, Bruce Y.']",,,,
,PMC,Ebola Virus Disease in West Africa — The First 9 Months of the Epidemic and Forward Projections,http://dx.doi.org/10.1056/NEJMoa1411100,PMC4235004,,,"BACKGROUND: On March 23, 2014, the World Health Organization (WHO) was notified of an out-break of Ebola virus disease (EVD) in Guinea. On August 8, the WHO declared the epidemic to be a “public health emergency of international concern.” METHODS: By September 14, 2014, a total of 4507 probable and confirmed cases, including 2296 deaths from EVD (Zaire species) had been reported from five countries in West Africa — Guinea, Liberia, Nigeria, Senegal, and Sierra Leone. We analyzed a detailed subset of data on 3343 confirmed and 667 probable Ebola cases collected in Guinea, Liberia, Nigeria, and Sierra Leone as of September 14. RESULTS: The majority of patients are 15 to 44 years of age (49.9% male), and we estimate that the case fatality rate is 70.8% (95% confidence interval [CI], 69 to 73) among persons with known clinical outcome of infection. The course of infection, including signs and symptoms, incubation period (11.4 days), and serial interval (15.3 days), is similar to that reported in previous outbreaks of EVD. On the basis of the initial periods of exponential growth, the estimated basic reproduction numbers (R(0)) are 1.71 (95% CI, 1.44 to 2.01) for Guinea, 1.83 (95% CI, 1.72 to 1.94) for Liberia, and 2.02 (95% CI, 1.79 to 2.26) for Sierra Leone. The estimated current reproduction numbers (R) are 1.81 (95% CI, 1.60 to 2.03) for Guinea, 1.51 (95% CI, 1.41 to 1.60) for Liberia, and 1.38 (95% CI, 1.27 to 1.51) for Sierra Leone; the corresponding doubling times are 15.7 days (95% CI, 12.9 to 20.3) for Guinea, 23.6 days (95% CI, 20.2 to 28.2) for Liberia, and 30.2 days (95% CI, 23.6 to 42.3) for Sierra Leone. Assuming no change in the control measures for this epidemic, by November 2, 2014, the cumulative reported numbers of confirmed and probable cases are predicted to be 5740 in Guinea, 9890 in Liberia, and 5000 in Sierra Leone, exceeding 20,000 in total. CONCLUSIONS: These data indicate that without drastic improvements in control measures, the numbers of cases of and deaths from EVD are expected to continue increasing from hundreds to thousands per week in the coming months.",,,,,,
,PMC,Design and Evaluation of Thioalkylated Mannose-Modified Dendrimer (G3)/α-Cyclodextrin Conjugates as Antigen-Presenting Cell-Selective siRNA Carriers,http://dx.doi.org/10.1208/s12248-014-9665-9,PMC4389755,,,"To design and evaluate the potential use of thioalkylated mannose-modified dendrimer (generation 3; G3) conjugates with α-cyclodextrin (Man-S-α-CDE (G3)) as novel antigen-presenting cell (APC)-selective siRNA carriers, we investigated the RNAi effects of siRNA complexes with Man-S-α-CDEs (G3). Man-S-α-CDE (G3, average degree of substitution of mannose (DSM) 4)/siRNA complex had the potent RNAi effects in both NR8383 cells, a rat alveolar macrophage cell line, and JAWSII cells, a mouse dendritic cell line, through adequate physicochemical properties, mannose receptor (MR)-mediated cellular uptake, and efficient phagosomal escape of the siRNA complex. In addition, cytotoxic activities of the siRNA complexes with α-CDE (G3, DS2) and Man-S-α-CDE (G3, DSM4) were almost negligible up to a charge ratio of 100 (carrier/siRNA). Taken together, these results suggest that Man-S-α-CDE (G3, DSM4) has the potential for a novel APC-selective siRNA carrier. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1208/s12248-014-9665-9) contains supplementary material, which is available to authorized users.",,"['Motoyama, Keiichi', 'Mitsuyasu, Ryosuke', 'Akao, Chiho', 'Tanaka, Takahiro', 'Ohyama, Ayumu', 'Sato, Nana', 'Higashi, Taishi', 'Arima, Hidetoshi']",,,,
,PMC,The Role of Multiplex PCR in Respiratory Tract Infections in Children,http://dx.doi.org/10.3238/arztebl.2014.0639,PMC4199249,,,"BACKGROUND: Infants, toddlers, and children of primary-school age without any special risk factors generally have three to ten febrile respiratory infections per year. Most such infections are of viral origin and self-limiting, but viral infection is often hard to distinguish from bacterial infection. The use of a multiplex polymerase chain reaction (PCR) to detect viruses in respiratory secretions is potentially beneficial, as it might help physicians avoid giving antibiotics unnecessarily. METHODS: This article is based on a selective review of the literature and on the findings of the authors‘ own investigations. RESULTS: Multiplex PCR is a highly sensitive, highly specific test for the detection of viral nucleic acids in respiratory secretions. If PCR reveals the presence of RNA derived from respiratory syncytial virus, human metapneumovirus, parainfluenza virus, or influenza virus, then an acute infection caused by the corresponding pathogen is probably present, and further treatment can be given accordingly. On the other hand, the nucleic acids of adeno-, boca-, rhino- or coronaviruses can be found in relatively trivial infections as well as in asymptomatic persons, probably reflecting either a prior infection or a current subclinical one. For children in particular, upper respiratory infections are so common in the winter months that acute and prior infections with these pathogens cannot be distinguished by multiplex PCR. The use of multiplex PCR in children has not been shown to shorten hospital stays or to lessen antibiotic consumption or overall cost. CONCLUSION: The detectability of viral nucleic acids is an important contribution to the diagnostic assessment of children with severe respiratory infection. For these highly sensitive diagnostic tests to be used optimally, primary viral infections must be distinguished from bacterial superinfections.",,"['Krause, Jens Christian', 'Panning, Marcus', 'Hengel, Hartmut', 'Henneke, Philipp']",,,,
,PMC,Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments – the importance of immunofocusing in subunit vaccine design,http://dx.doi.org/10.1016/j.vaccine.2014.08.086,PMC4194190,,,"The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is currently spreading among humans, making development of effective MERS vaccines a high priority. A defined receptor-binding domain (RBD) in MERS-CoV spike protein can potentially serve as a subunit vaccine candidate against MERS-CoV infections. To identify an ideal vaccine candidate, we have constructed five different versions of RBD fragments, S350-588-Fc, S358-588-Fc, S367-588-Fc, S367-606-Fc, and S377-588-Fc (their names indicate their residue range in the spike protein and their C-terminal Fc tag), and further investigated their receptor binding affinity, antigenicity, immunogenicity, and neutralizing potential. The results showed that S377-588-Fc is among the RBD fragments that demonstrated the highest DPP4-binding affinity and induced the highest-titer IgG antibodies in mice. In addition, S377-588-Fc elicited higher-titer neutralizing antibodies than all the other RBD fragments in mice, and also induced high-titer neutralizing antibodies in immunized rabbits. Structural analysis suggests that S377-588-Fc contains the stably folded RBD structure, the full receptor-binding site, and major neutralizing epitopes, such that additional structures to this fragment introduce non-neutralizing epitopes and may also alter the tertiary structure of the RBD. Taken together, our data suggest that the RBD fragment encompassing spike residues 377-588 is a critical neutralizing receptor-binding fragment and an ideal candidate for development of effective MERS vaccines, and that adding non-neutralizing structures to this RBD fragment diminishes its neutralizing potential. Therefore, in viral vaccine design, it is important to identify the most stable and neutralizing viral RBD fragment, while eliminating unnecessary and non-neutralizing structures, as a means of “immunofocusing”.",,"['Ma, Cuiqing', 'Wang, Lili', 'Tao, Xinrong', 'Zhang, Naru', 'Yang, Yang', 'Tseng, Chien-Te K', 'Li, Fang', 'Zhou, Yusen', 'Jiang, Shibo', 'Du, Lanying']",,,,
,PMC,One Bioregion/One Health: An Integrative Narrative for Transboundary Planning along the US–Mexico Border,http://dx.doi.org/10.1080/13600826.2014.951316,PMC4470564,,,"Global megatrends—including climate change, food and water insecurity, economic crisis, large-scale disasters and widespread increases in preventable diseases—are motivating a bioregionalisation of planning in city-regions around the world. Bioregionalisation is an emergent process. It is visible where societies have begun grappling with complex socio-ecological problems by establishing place-based (territorial) approaches to securing health and well-being. This article examines a bioregional effort to merge place-based health planning and ecological restoration along the US–Mexico border. The theoretical construct underpinning this effort is called One Bioregion/One Health (OBROH). OBROH frames health as a transborder phenomenon that involves human-animal-environment interactions. The OBROH approach aims to improve transborder knowledge networking, ecosystem resilience, community participation in science–society relations, leadership development and cross-disciplinary training. It is a theoretically informed narrative to guide action. OBROH is part of a paradigm shift evident worldwide; it is redefining human-ecological relationships in the quest for healthy place making. The article concludes on a forward-looking note about the promise of environmental epidemiology, telecoupling, ecological restoration, the engaged university and bioregional justice as concepts pertinent to reinventing place-based planning.",,"['PEZZOLI, KEITH', 'KOZO, JUSTINE', 'FERRAN, KAREN', 'WOOTEN, WILMA', 'GOMEZ, GUDELIA RANGEL', 'AL-DELAIMY, WAEL K.']",,,,
,PMC,PNAS Plus Significance Statements,http://dx.doi.org/10.1073/pnas.ss11137,PMC4169913,,,,,,,,,
,PMC,Rapid viral diagnosis for acute febrile respiratory illness in children in the Emergency Department,http://dx.doi.org/10.1002/14651858.CD006452.pub4,PMC6718218,,,"BACKGROUND: Pediatric acute respiratory infections (ARIs) represent a significant burden on pediatric Emergency Departments (EDs) and families. Most of these illnesses are due to viruses. However, investigations (radiography, blood, and urine testing) to rule out bacterial infections and antibiotics are often ordered because of diagnostic uncertainties. This results in prolonged ED visits and unnecessary antibiotic use. The risk of concurrent bacterial infection has been reported to be negligible in children over three months of age with a confirmed viral infection. Rapid viral testing in the ED may alleviate the need for precautionary testing and antibiotic use. OBJECTIVES: To determine if the use of a rapid viral detection test for children with an acute respiratory infection (ARI) in Emergency Departments (EDs) changes patient management and resource use in the ED, compared to not using a rapid viral detection test. We hypothesized that rapid viral testing reduces antibiotic use in the ED as well as reduces the rate of ancillary testing and length of ED visits. SEARCH METHODS: We searched CENTRAL (2014, Issue 6), MEDLINE (1950 to July week 1, 2014), MEDLINE In‐Process & Other Non‐Indexed Citations (15 July 2014), EMBASE.com (1988 to July 2014), HealthStar (1966 to 2009), BIOSIS Previews (1969 to July 2014), CAB Abstracts (1973 to July 2014), CBCA Reference (1970 to 2007) and ProQuest Dissertations and Theses (1861 to 2009). SELECTION CRITERIA: Randomized controlled trials (RCTs) of rapid viral testing for children with ARIs in the ED. DATA COLLECTION AND ANALYSIS: Two review authors used the inclusion criteria to select trials, evaluate their quality, and extract data. We obtained missing data from trial authors. We expressed differences in rate of investigations and antibiotic use as risk ratios (RRs), and expressed difference in ED length of visits as mean differences (MDs), with 95% confidence intervals (CIs). MAIN RESULTS: No new trials were identified in this 2014 update. We included four trials (three RCTs and one quazi‐RCT), with 759 children in the rapid viral testing group and 829 in the control group. Three out of the four studies were comparable in terms of young age of participants, with one study increasing the age of inclusion up to five years of age. All studies included either fever or respiratory symptoms as inclusion criteria (two required both, one required fever or respiratory symptoms, and one required only fever). All studies were comparable in terms of exclusion criteria, intervention, and outcome data. In terms of risk of bias, one study failed to utilize a random sequence generator, one study did not comment on completeness of outcome data, and only one of four studies included allocation concealment as part of the study design. None of the studies definitively blinded participants. Rapid viral testing resulted in a trend toward decreased antibiotic use in the ED, but this was not statistically significant. We found lower rates of chest radiography (RR 0.77, 95% CI 0.65 to 0.91) in the rapid viral testing group, but no effect on length of ED visits, or blood or urine testing in the ED. No study made mention of any adverse effects related to viral testing. AUTHORS' CONCLUSIONS: There is insufficient evidence to support routine rapid viral testing to reduce antibiotic use in pediatric EDs. Rapid viral testing may or may not reduce rates of antibiotic use, and other investigations (urine and blood testing); these studies do not provide enough power to resolve this question. However, rapid viral testing does reduce the rate of chest X‐rays in the ED. An adequately powered trial with antibiotic use as an outcome is needed.",,"['Doan, Quynh', 'Enarson, Paul', 'Kissoon, Niranjan', 'Klassen, Terry P', 'Johnson, David W']",,,,
,PMC,Coping with future epidemics: Tai chi practice as an overcoming strategy used by survivors of severe acute respiratory syndrome (SARS) in post‐SARS Hong Kong,http://dx.doi.org/10.1111/hex.12270,PMC5055248,,,"BACKGROUND: Although SARS had been with a controversial topic for a decade at the time of this study, numerous SARS survivors had not yet physically, psychologically or socially recovered from the aftermath of SARS. Among chronically ill patients, the use of complementary and alternative medicine (CAM) is reported to be widespread. However, extremely little is known about the use of CAM by SARS survivors in the post‐SARS period and even less is known about how the use of CAM is related to the unpleasant social and medical‐treatment experiences of SARS survivors, their eagerness to re‐establish social networks, and their awareness to prepare for future epidemics. OBJECTIVE: To investigate the motivations for practising tai chi among SARS survivors in post‐SARS Hong Kong. DESIGN, SETTING AND PARTICIPANTS: Using a qualitative approach, I conducted individual semi‐structured interviews with 35 SARS survivors, who were purposively sampled from a tai chi class of a SARS‐patient self‐help group in Hong Kong. RESULTS: Health concerns and social experiences motivated the participants to practise tai chi in post‐SARS Hong Kong. Experiencing health deterioration in relation to SARS‐associated sequelae, coping with unpleasant experiences during follow‐up biomedical treatments, a desire to regain an active role in recovery and rehabilitation, overcoming SARS‐associated stigmas by establishing a new social network and preparing for potential future stigmatization and discrimination were the key motivators for them. CONCLUSION: The participants practised tai chi not only because they sought to improve their health but also because it provided a crucial social function and meaning to them.",,"Siu, Judy Yuen‐man",,,,
,PMC,Oral Delivery of Angiotensin-Converting Enzyme 2 and Angiotensin-(1-7) Bioencapsulated in Plant Cells Attenuates Pulmonary Hypertension,http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.03871,PMC4239698,,,"Emerging evidences indicate that diminished activity of the vasoprotective axis of the renin–angiotensin system, constituting angiotensin-converting enzyme 2 (ACE2) and its enzymatic product, angiotensin-(1-7) [Ang-(1-7)] contribute to the pathogenesis of pulmonary hypertension (PH). However, long-term repetitive delivery of ACE2 or Ang-(1-7) would require enhanced protein stability and ease of administration to improve patient compliance. Chloroplast expression of therapeutic proteins enables their bioencapsulation within plant cells to protect against gastric enzymatic degradation and facilitates long-term storage at room temperature. Besides, fusion to a transmucosal carrier helps effective systemic absorption from the intestine on oral delivery. We hypothesized that bioencapsulating ACE2 or Ang-(1-7) fused to the cholera nontoxin B subunit would enable development of an oral delivery system that is effective in treating PH. PH was induced in male Sprague Dawley rats by monocrotaline administration. Subset of animals was simultaneously treated with bioencapsulaed ACE2 or Ang-(1-7) (prevention protocol). In a separate set of experiments, drug treatment was initiated after 2 weeks of PH induction (reversal protocol). Oral feeding of rats with bioencapsulated ACE2 or Ang-(1-7) prevented the development of monocrotaline-induced PH and improved associated cardiopulmonary pathophysiology. Furthermore, in the reversal protocol, oral ACE2 or Ang-(1-7) treatment significantly arrested disease progression, along with improvement in right heart function, and decrease in pulmonary vessel wall thickness. In addition, a combination therapy with ACE2 and Ang-(1-7) augmented the beneficial effects against monocrotaline-induced lung injury. Our study provides proof-of-concept for a novel low-cost oral ACE2 or Ang-(1-7) delivery system using transplastomic technology for pulmonary disease therapeutics.",,"['Shenoy, Vinayak', 'Kwon, Kwang-Chul', 'Rathinasabapathy, Anandharajan', 'Lin, Shina', 'Jin, Guiying', 'Song, Chunjuan', 'Shil, Pollob', 'Nair, Anand', 'Qi, Yanfei', 'Li, Qiuhong', 'Francis, Joseph', 'Katovich, Michael J.', 'Daniell, Henry', 'Raizada, Mohan K.']",,,,
,PMC,Angiotensin-II mediates ACE2 Internalization and Degradation through an Angiotensin-II type I receptor-dependent mechanism,http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.03743,PMC4231883,,,"Angiotensin Converting Enzyme type 2 (ACE2) is a pivotal component of the renin-angiotensin system, promoting the conversion of Angiotensin (Ang)-II to Ang-(1-7). We previously reported that decreased ACE2 expression and activity contribute to the development of Ang-II-mediated hypertension in mice. The present study aimed to investigate the mechanisms involved in ACE2 down-regulation during neurogenic hypertension. In ACE2-transfected Neuro-2A cells, Ang-II treatment resulted in a significant attenuation of ACE2 enzymatic activity. Examination of the subcellular localization of ACE2 revealed that Ang-II treatment leads to ACE2 internalization and degradation into lysosomes. These effects were prevented by both the Ang-II type 1 receptor (AT(1)R) blocker losartan and the lysosomal inhibitor leupeptin. In contrast, in HEK293T cells, which lack endogenous AT(1)R, Ang-II failed to promote ACE2 internalization. Moreover, this effect could be induced after AT(1)R transfection. Further, co-immunoprecipitation experiments demonstrated that AT(1)R and ACE2 form complexes and these interactions were decreased by Ang-II treatment, which also enhanced ACE2 ubiquitination. In contrast, ACE2 activity was not changed by transfection of AT(2) or Mas receptors. In vivo, Ang-II-mediated hypertension was blunted by chronic infusion of leupeptin in wildtype C57Bl/6, but not in ACE2 knockout mice. Overall, this is the first demonstration that elevated Ang-II levels reduce ACE2 expression and activity by stimulation of lysosomal degradation through an AT(1)R-dependent mechanism.",,"['Deshotels, Matthew R.', 'Xia, Huijing', 'Sriramula, Srinivas', 'Lazartigues, Eric', 'Filipeanu, Catalin M.']",,,,
,PMC,Safety and Immunogenicity of DNA Vaccines Encoding Ebolavirus and Marburgvirus Wild-Type Glycoproteins in a Phase I Clinical Trial,http://dx.doi.org/10.1093/infdis/jiu511,PMC4318920,,,"BACKGROUND: Ebolavirus and Marburgvirus cause severe hemorrhagic fever with high mortality and are potential bioterrorism agents. There are no available vaccines or therapeutic agents. Previous clinical trials evaluated transmembrane-deleted and point-mutation Ebolavirus glycoproteins (GPs) in candidate vaccines. Constructs evaluated in this trial encode wild-type (WT) GP from Ebolavirus Zaire and Sudan species and the Marburgvirus Angola strain expressed in a DNA vaccine. METHODS: The VRC 206 study evaluated the safety and immunogenicity of these DNA vaccines (4 mg administered intramuscularly by Biojector) at weeks 0, 4, and 8, with a homologous boost at or after week 32. Safety evaluations included solicited reactogenicity and coagulation parameters. Primary immune assessment was done by means of GP-specific enzyme-linked immunosorbent assay. RESULTS: The vaccines were well tolerated, with no serious adverse events; 80% of subjects had positive enzyme-linked immunosorbent assay results (≥30) at week 12. The fourth DNA vaccination boosted the immune responses. CONCLUSIONS: The investigational Ebolavirus and Marburgvirus WT GP DNA vaccines were safe, well tolerated, and immunogenic in this phase I study. These results will further inform filovirus vaccine research toward a goal of inducing protective immunity by using WT GP antigens in candidate vaccine regimens. CLINICAL TRIALS REGISTRATION: NCT00605514.",,"['Sarwar, Uzma N.', 'Costner, Pamela', 'Enama, Mary E.', 'Berkowitz, Nina', 'Hu, Zonghui', 'Hendel, Cynthia S.', 'Sitar, Sandra', 'Plummer, Sarah', 'Mulangu, Sabue', 'Bailer, Robert T.', 'Koup, Richard A.', 'Mascola, John R.', 'Nabel, Gary J.', 'Sullivan, Nancy J.', 'Graham, Barney S.', 'Ledgerwood, Julie E.']",,,,
,PMC,Social Vulnerability Index for the Older People—Hong Kong and New York City as Examples,http://dx.doi.org/10.1007/s11524-014-9901-8,PMC4242856,,,"Many world cities have suffered large-scale disasters, causing a significant loss of lives, property damage, and adverse social and economic impact. Those who are most vulnerable during and in the immediate aftermath of disaster crises are the elderly. Therefore, it is imperative to identify them and determine their specific needs in order to support them. Although several Social Vulnerability Indexes (SVIs) have been developed to assess different types of disaster vulnerability across geographic and population levels, few have been tailored to the older population. Building on the research of Gusmano et al., this study modifies and uses an SVI specifically designed to assess the vulnerability of older populations to emergencies and disasters across seven domains, namely, population size, institutionalization, poverty, living alone, disability, communication obstacles, and access to primary care. Moreover, it is acknowledged that availability of data largely depends on the local context and is always a barrier to production of indices across countries. The present study offers suggestions on how modifications can be made for local adaptation such that the SVI can be applied in different cities and localities. The SVI used in this study provides information to stakeholders in emergency preparedness, not only about natural disasters but also about health hazards and emergencies, which few existing SVI address.",,"['Chau, Pui Hing', 'Gusmano, Michael K.', 'Cheng, Joanna O. Y.', 'Cheung, Sai Hei', 'Woo, Jean']",,,,
,PMC,"Emerging, evolving, and established infectious diseases and interventions",http://dx.doi.org/10.1126/science.1254166,PMC4408765,,,,,"['Halloran, M. Elizabeth', 'Longini, Ira M.']",,,,
,PMC,"RNA Virus Population Diversity, an Optimum for Maximal Fitness and Virulence",http://dx.doi.org/10.1074/jbc.M114.592303,PMC4207971,,,"The ability of an RNA virus to exist as a population of genetically distinct variants permits the virus to overcome events during infections that would otherwise limit virus multiplication or drive the population to extinction. Viral genetic diversity is created by the ribonucleotide misincorporation frequency of the viral RNA-dependent RNA polymerase (RdRp). We have identified a poliovirus (PV) RdRp derivative (H273R) possessing a mutator phenotype. GMP misincorporation efficiency for H273R RdRp in vitro was increased by 2–3-fold that manifested in a 2–3-fold increase in the diversity of the H273R PV population in cells. Circular sequencing analysis indicated that some mutations were RdRp-independent. Consistent with the population genetics theory, H273R PV was driven to extinction more easily than WT in cell culture. Furthermore, we observed a substantial reduction in H273R PV virulence, measured as the ability to cause paralysis in the cPVR mouse model. Reduced virulence correlated with the inability of H273R PV to sustain replication in tissues/organs in which WT persists. Despite the attenuated phenotype, H273R PV was capable of replicating in mice to levels sufficient to induce a protective immune response, even when the infecting dose used was insufficient to elicit any visual signs of infection. We conclude that optimal RdRp fidelity is a virulence determinant that can be targeted for viral attenuation or antiviral therapies, and we suggest that the RdRp may not be the only source of mutations in a RNA virus genome.",,"['Korboukh, Victoria K.', 'Lee, Cheri A.', 'Acevedo, Ashley', 'Vignuzzi, Marco', 'Xiao, Yinghong', 'Arnold, Jamie J.', 'Hemperly, Stephen', 'Graci, Jason D.', 'August, Avery', 'Andino, Raul', 'Cameron, Craig E.']",,,,
,PMC,Neutralization of Virus Infectivity by Antibodies: Old Problems in New Perspectives,http://dx.doi.org/10.1155/2014/157895,PMC4835181,,,"Neutralizing antibodies (NAbs) can be both sufficient and necessary for protection against viral infections, although they sometimes act in concert with cellular immunity. Successful vaccines against viruses induce NAbs but vaccine candidates against some major viral pathogens, including HIV-1, have failed to induce potent and effective such responses. Theories of how antibodies neutralize virus infectivity have been formulated and experimentally tested since the 1930s; and controversies about the mechanistic and quantitative bases for neutralization have continually arisen. Soluble versions of native oligomeric viral proteins that mimic the functional targets of neutralizing antibodies now allow the measurement of the relevant affinities of NAbs. Thereby the neutralizing occupancies on virions can be estimated and related to the potency of the NAbs. Furthermore, the kinetics and stoichiometry of NAb binding can be compared with neutralizing efficacy. Recently, the fundamental discovery that the intracellular factor TRIM21 determines the degree of neutralization of adenovirus has provided new mechanistic and quantitative insights. Since TRIM21 resides in the cytoplasm, it would not affect the neutralization of enveloped viruses, but its range of activity against naked viruses will be important to uncover. These developments bring together the old problems of virus neutralization—mechanism, stoichiometry, kinetics, and efficacy—from surprising new angles.",,"Klasse, P. J.",,,,
,PMC,Symptomatic and Asymptomatic Respiratory Viral Infections in the First Year of Life: Association With Acute Otitis Media Development,http://dx.doi.org/10.1093/cid/ciu714,PMC4318943,,,"Background. Sensitive diagnostic assays have increased the detection of viruses in asymptomatic individuals. The clinical significance of asymptomatic respiratory viral infection in infants is unknown. Methods. High-throughput, quantitative polymerase chain reaction assays were used to detect 13 common respiratory viruses from nasopharyngeal specimens collected during 2028 visits from 362 infants followed from near birth up to 12 months of age. Specimens were collected at monthly interval (months 1–6 and month 9) and during upper respiratory tract infection (URTI) episodes. Subjects were followed closely for acute otitis media (AOM) development. Results. Viruses were detected in 76% of 394 URTI specimens and 27% of asymptomatic monthly specimens. Rhinovirus was detected most often; multiple viruses were detected in 29% of the specimens. Generalized mixed-model analyses associated symptoms with increasing age and female sex; detection of respiratory syncytial virus (RSV), influenza, rhinovirus, metapneumovirus, and adenovirus was highly associated with symptoms. Increasing age was also associated with multiple virus detection. Overall, 403 asymptomatic viral infections in 237 infants were identified. Viral load was significantly higher in URTI specimens than asymptomatic specimens but did not differentiate cases of URTI with and without AOM complication. The rate of AOM complicating URTI was 27%; no AOM occurred following asymptomatic viral infections. AOM development was associated with increasing age and infection with RSV, rhinovirus, enterovirus, adenovirus, and bocavirus. Conclusions. Compared to symptomatic infection, asymptomatic viral infection in infants is associated with young age, male sex, low viral load, specific viruses, and single virus detection. Asymptomatic viral infection did not result in AOM.",,"['Chonmaitree, Tasnee', 'Alvarez-Fernandez, Pedro', 'Jennings, Kristofer', 'Trujillo, Rocio', 'Marom, Tal', 'Loeffelholz, Michael J.', 'Miller, Aaron L.', 'McCormick, David P.', 'Patel, Janak A.', 'Pyles, Richard B.']",,,,
,PMC,"Global Polio Eradication: Espionage, Disinformation, and the Politics of Vaccination",http://dx.doi.org/10.1111/1468-0009.12065,PMC4221744,,,,,"Gostin, Lawrence O",,,,
,PMC,Inner Workings: The strictest biosafety,http://dx.doi.org/10.1073/pnas.1413974111,PMC4246971,,,,,"Dance, Amber",,,,
,PMC,Knowledge about pandemic influenza preparedness among vulnerable migrants in Thailand,http://dx.doi.org/10.1093/heapro/dau074,PMC4745616,,,"This study was designed to assess factors associated with a high level of knowledge about influenza among displaced persons and labor migrants in Thailand. We conducted a cross-sectional study of 797 documented and undocumented migrants thought to be vulnerable to influenza during the early stages of the 2009 H1N1 pandemic. Data were collected on socio-demographic factors, migration status, health information sources, barriers to accessing public healthcare services and influenza-related knowledge using a 201-item interviewer-assisted questionnaire. Among the different types of influenza, participants' awareness of avian influenza was greatest (81%), followed by H1N1 (78%), human influenza (61%) and pandemic influenza (35%). Logistic regression analyses identified 11 factors that significantly predicted a high level of knowledge about influenza. Six or more years of education completed [odds ratio (OR) 6.89 (95% confidence interval (CI) 3.58–13.24)] and recent participation in an influenza prevention activity [OR 5.27 (95% CI 2.78–9.98)] were the strongest predictors. Recommendations to aid public health efforts toward pandemic mitigation and prevention include increasing accessibility of education options for migrants and increasing frequency and accessibility of influenza prevention activities, such as community outreach and meetings. Future research should seek to identify which influenza prevention activities and education materials are most effective.",,"['Hickey, Jason E.', 'Gagnon, Anita J.', 'Jitthai, Nigoon']",,,,
,PMC,Early Epidemic Dynamics of the West African 2014 Ebola Outbreak: Estimates Derived with a Simple Two-Parameter Model,http://dx.doi.org/10.1371/currents.outbreaks.89c0d3783f36958d96ebbae97348d571,PMC4169344,25642358,CC BY,"The 2014 West African Ebola virus outbreak, now more correctly referred to as an epidemic, is the largest ever to occur. As of August 28, 2014, concerns have been raised that control efforts, particularly in Liberia, have been ineffective, as reported case counts continue to increase. Limited data are available on the epidemiology of the outbreak. However, reported cumulative incidence data as well as death counts are available for Guinea, Sierra Leone, Liberia and Nigeria. We utilized a simple, two parameter mathematical model of epidemic growth and control, to characterize epidemic growth patterns in West Africa, to evaluate the degree to which the epidemic is being controlled, and to assess the potential implications of growth patterns for epidemic size. Models demonstrated good fits to data. Overall basic reproductive number (R0) for the epidemic was estimated to be between 1.6 and 2.0, consistent with prior outbreaks. However, we identified only weak evidence for the occurrence of epidemic control in West Africa as a whole, and essentially no evidence for control in Liberia (though slowing of growth was seen in Guinea and Sierra Leone). It is projected that small reductions in transmission would prevent tens of thousands of future infections. These findings suggest that there is an extraordinary need for improved control measures for the 2014 Ebola epidemic, especially in Liberia, if catastrophe is to be averted.",2014 Sep 8,"['Fisman, David', 'Khoo, Edwin', 'Tuite, Ashleigh']",PLoS Curr,,,
,PMC,Middle East Respiratory Syndrome and Blood Donation: Topic for Further Study and Discussion,http://dx.doi.org/10.1007/s12288-014-0453-6,PMC4925468,,,,,"Wiwanitkit, Viroj",,,,
,PMC,Anatomy and Neurophysiology of Cough: CHEST Guideline and Expert Panel Report,http://dx.doi.org/10.1378/chest.14-1481,PMC4251621,,,"Bronchopulmonary C-fibers and a subset of mechanically sensitive, acid-sensitive myelinated sensory nerves play essential roles in regulating cough. These vagal sensory nerves terminate primarily in the larynx, trachea, carina, and large intrapulmonary bronchi. Other bronchopulmonary sensory nerves, sensory nerves innervating other viscera, as well as somatosensory nerves innervating the chest wall, diaphragm, and abdominal musculature regulate cough patterning and cough sensitivity. The responsiveness and morphology of the airway vagal sensory nerve subtypes and the extrapulmonary sensory nerves that regulate coughing are described. The brainstem and higher brain control systems that process this sensory information are complex, but our current understanding of them is considerable and increasing. The relevance of these neural systems to clinical phenomena, such as urge to cough and psychologic methods for treatment of dystussia, is high, and modern imaging methods have revealed potential neural substrates for some features of cough in the human.",,"['Canning, Brendan J.', 'Chang, Anne B.', 'Bolser, Donald C.', 'Smith, Jaclyn A.', 'Mazzone, Stuart B.', 'McGarvey, Lorcan', None]",,,,
,PMC,Understanding the Development and Perception of Global Health for More Effective Student Education,,PMC4144278,,,"The concept of “global health” that led to the establishment of the World Health Organization in the 1940s is still promoting a global health movement 70 years later. Today’s global health acts first as a guiding principle for our effort to improve people’s health across the globe. Furthermore, global health has become a branch of science, “global health science,” supporting institutionalized education. Lastly, as a discipline, global health should focus on medical and health issues that: 1) are determined primarily by factors with a cross-cultural, cross-national, cross-regional, or global scope; 2) are local but have global significance if not appropriately managed; and 3) can only be efficiently managed through international or global efforts. Therefore, effective global health education must train students 1) to understand global health status; 2) to investigate both global and local health issues with a global perspective; and 3) to devise interventions to deal with these issues.",,"Chen, Xinguang",,,,
,PMC,One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities,http://dx.doi.org/10.1073/pnas.1323705111,PMC4169972,,,"In addition to members causing milder human infections, the Coronaviridae family includes potentially lethal zoonotic agents causing severe acute respiratory syndrome (SARS) and the recently emerged Middle East respiratory syndrome. The ∼30-kb positive-stranded RNA genome of coronaviruses encodes a replication/transcription machinery that is unusually complex and composed of 16 nonstructural proteins (nsps). SARS-CoV nsp12, the canonical RNA-dependent RNA polymerase (RdRp), exhibits poorly processive RNA synthesis in vitro, at odds with the efficient replication of a very large RNA genome in vivo. Here, we report that SARS-CoV nsp7 and nsp8 activate and confer processivity to the RNA-synthesizing activity of nsp12. Using biochemical assays and reverse genetics, the importance of conserved nsp7 and nsp8 residues was probed. Whereas several nsp7 mutations affected virus replication to a limited extent, the replacement of two nsp8 residues (P183 and R190) essential for interaction with nsp12 and a third (K58) critical for the interaction of the polymerase complex with RNA were all lethal to the virus. Without a loss of processivity, the nsp7/nsp8/nsp12 complex can associate with nsp14, a bifunctional enzyme bearing 3′-5′ exoribonuclease and RNA cap N7-guanine methyltransferase activities involved in replication fidelity and 5′-RNA capping, respectively. The identification of this tripartite polymerase complex that in turn associates with the nsp14 proofreading enzyme sheds light on how coronaviruses assemble an RNA-synthesizing machinery to replicate the largest known RNA genomes. This protein complex is a fascinating example of the functional integration of RNA polymerase, capping, and proofreading activities.",,"['Subissi, Lorenzo', 'Posthuma, Clara C.', 'Collet, Axelle', 'Zevenhoven-Dobbe, Jessika C.', 'Gorbalenya, Alexander E.', 'Decroly, Etienne', 'Snijder, Eric J.', 'Canard, Bruno', 'Imbert, Isabelle']",,,,
,PMC,New Methods in Tissue Engineering: Improved Models for Viral Infection,http://dx.doi.org/10.1146/annurev-virology-031413-085437,PMC4398347,,,"New insights in the study of virus and host biology in the context of viral infection are made possible by the development of model systems that faithfully recapitulate the in vivo viral life cycle. Standard tissue culture models lack critical emergent properties driven by cellular organization and in vivo–like function, whereas animal models suffer from limited susceptibility to relevant human viruses and make it difficult to perform detailed molecular manipulation and analysis. Tissue engineering techniques may enable virologists to create infection models that combine the facile manipulation and readouts of tissue culture with the virus-relevant complexity of animal models. Here, we review the state of the art in tissue engineering and describe how tissue engineering techniques may alleviate some common shortcomings of existing models of viral infection, with a particular emphasis on hepatotropic viruses. We then discuss possible future applications of tissue engineering to virology, including current challenges and potential solutions.",,"['Ramanan, Vyas', 'Scull, Margaret A.', 'Sheahan, Timothy P.', 'Rice, Charles M.', 'Bhatia, Sangeeta N.']",,,,
,PMC,Signaling of Chloroquine-Induced Stress in the Yeast Saccharomyces cerevisiae Requires the Hog1 and Slt2 Mitogen-Activated Protein Kinase Pathways,http://dx.doi.org/10.1128/AAC.02393-13,PMC4135872,,,"Chloroquine (CQ) has been under clinical use for several decades, and yet little is known about CQ sensing and signaling mechanisms or about their impact on various biological pathways. We employed the budding yeast Saccharomyces cerevisiae as a model organism to study the pathways targeted by CQ. Our screening with yeast mutants revealed that it targets histone proteins and histone deacetylases (HDACs). Here, we also describe the novel role of mitogen-activated protein kinases Hog1 and Slt2, which aid in survival in the presence of CQ. Cells deficient in Hog1 or Slt2 are found to be CQ hypersensitive, and both proteins were phosphorylated in response to CQ exposure. CQ-activated Hog1p is translocated to the nucleus and facilitates the expression of GPD1 (glycerol-3-phosphate dehydrogenase), which is required for the synthesis of glycerol (one of the major osmolytes). Moreover, cells treated with CQ exhibited an increase in intracellular reactive oxygen species (ROS) levels and the effects were rescued by addition of reduced glutathione to the medium. The deletion of SOD1, the superoxide dismutase in yeast, resulted in hypersensitivity to CQ. We have also observed P38 as well as P42/44 phosphorylation in HEK293T human cells upon exposure to CQ, indicating that the kinds of responses generated in yeast and human cells are similar. In summary, our findings define the multiple biological pathways targeted by CQ that might be useful for understanding the toxicity modulated by this pharmacologically important molecule.",,"['Baranwal, Shivani', 'Azad, Gajendra Kumar', 'Singh, Vikash', 'Tomar, Raghuvir S.']",,,,
,PMC,"Regulatory Underpinnings of Global Health Security: FDA's Roles in Preventing, Detecting, and Responding to Global Health Threats",http://dx.doi.org/10.1089/bsp.2014.0046,PMC4171126,,,"In February 2014, health officials from around the world announced the Global Health Security Agenda, a critical effort to strengthen national and global systems to prevent, detect, and respond to infectious disease threats and to foster stronger collaboration across borders. With its increasing global roles and broad range of regulatory responsibilities in ensuring the availability, safety, and security of medical and food products, the US Food and Drug Administration (FDA) is engaged in a range of efforts in support of global health security. This article provides an overview of FDA's global health security roles, focusing on its responsibilities related to the development and use of medical countermeasures (MCMs) for preventing, detecting, and responding to global infectious disease and other public health emergency threats. The article also discusses several areas—antimicrobial resistance, food safety, and supply chain integrity—in which FDA's global health security roles continue to evolve and extend beyond MCMs and, in some cases, beyond traditional infectious disease threats.",,"['Courtney, Brooke', 'Bond, Katherine C.', 'Maher, Carmen']",,,,
,PMC,Leveraging the Laboratory Response Network Model for the Global Health Security Agenda,http://dx.doi.org/10.1089/bsp.2014.0039,PMC4171117,,,"Promoting global health security as an international priority is a challenge; the US Centers for Disease Control and Prevention (CDC) in its Global Health Security Agenda has articulated the importance of accelerating progress toward a world safe and secure from infectious disease threats. The goals are to (1) prevent and reduce the likelihood of outbreaks—natural, accidental, or intentional; (2) detect threats early to save lives; and (3) respond rapidly and effectively using multisectoral, international coordination and communication. Foundational to this agenda is the World Health Organization (WHO) Revised International Health Regulations (IHR) of 2005, which provide the legal framework for countries to strengthen their health systems in order to be able to respond to any public health emergency of international concern. This article proposes leveraging the distributed structure of the US-managed Laboratory Response Network for Biological Threats Preparedness (LRN-B) to develop the core capacity of laboratory testing and to fulfill the laboratory-strengthening component of the Global Health Security Agenda. The LRN model offers an effective mechanism to detect and respond to public health emergencies of international concern.",,"['Mangal, Chris N.', 'Maryogo-Robinson, Lucy']",,,,
,PMC,One Health Security: An Important Component of the Global Health Security Agenda,http://dx.doi.org/10.1089/bsp.2014.0044,PMC4171112,,,"The objectives of the Global Health Security Agenda (GHSA) will require not only a “One Health” approach to counter natural disease threats against humans, animals, and the environment, but also a security focus to counter deliberate threats to human, animal, and agricultural health and to nations' economies. We have termed this merged approach “One Health Security.” It will require the integration of professionals with expertise in security, law enforcement, and intelligence to join the veterinary, agricultural, environmental, and human health experts essential to One Health and the GHSA. Working across such different professions, which occasionally have conflicting aims and different professional cultures, poses multiple challenges, but a multidisciplinary and multisectoral approach is necessary to prevent disease threats; detect them as early as possible (when responses are likely to be most effective); and, in the case of deliberate threats, find who may be responsible. This article describes 2 project areas that exemplify One Health Security that were presented at a workshop in January 2014: the US government and private industry efforts to reduce vulnerabilities to foreign animal diseases, especially foot-and-mouth disease; and AniBioThreat, an EU project to counter deliberate threats to agriculture by raising awareness and implementing prevention and response policies and practices.",,"['Gronvall, Gigi', 'Boddie, Crystal', 'Knutsson, Rickard', 'Colby, Michelle']",,,,
,PMC,Health Inequalities and Infectious Disease Epidemics: A Challenge for Global Health Security,http://dx.doi.org/10.1089/bsp.2014.0032,PMC4170985,,,"In today's global society, infectious disease outbreaks can spread quickly across the world, fueled by the rapidity with which we travel across borders and continents. Historical accounts of influenza pandemics and contemporary reports on infectious diseases clearly demonstrate that poverty, inequality, and social determinants of health create conditions for the transmission of infectious diseases, and existing health disparities or inequalities can further contribute to unequal burdens of morbidity and mortality. Yet, to date, studies of influenza pandemic plans across multiple countries find little to no recognition of health inequalities or attempts to engage disadvantaged populations to explicitly address the differential impact of a pandemic on them. To meet the goals and objectives of the Global Health Security Agenda, we argue that international partners, from WHO to individual countries, must grapple with the social determinants of health and existing health inequalities and extend their vision to include these factors so that disease that may start among socially disadvantaged subpopulations does not go unnoticed and spread across borders. These efforts will require rethinking surveillance systems to include sociodemographic data; training local teams of researchers and community health workers who are able to not only analyze data to recognize risk factors for disease, but also use simulation methods to assess the impact of alternative policies on reducing disease; integrating social science disciplines to understand local context; and proactively anticipating shortfalls in availability of adequate healthcare resources, including vaccines. Without explicit attention to existing health inequalities and underlying social determinants of health, the Global Health Security Agenda is unlikely to succeed in its goals and objectives.",,"['Quinn, Sandra Crouse', 'Kumar, Supriya']",,,,
,PMC,Strengthening Global Health Security by Developing Capacities to Deploy Medical Countermeasures Internationally,http://dx.doi.org/10.1089/bsp.2014.0049,PMC4170983,,,"In 2014, the United States in partnership with international organizations and nearly 30 partner countries launched the Global Health Security Agenda (GHSA) to accelerate progress to improve prevention, detection, and response capabilities for infectious disease outbreaks that can cause public health emergencies. Objective 9 of the GHSA calls for improved global access to medical countermeasures and establishes as a target the development of national policy frameworks for sending and receiving medical countermeasures from and to international partners during public health emergencies. The term medical countermeasures refers to vaccines, antimicrobials, therapeutics, and diagnostics that address the public health and medical consequences of chemical, biological, radiological, and nuclear events; pandemic influenza; and emerging infectious diseases. They are stockpiled by a few countries to protect their own populations and by international organizations, such as the World Health Organization (WHO), for the international community, typically for recipients with limited resources. However, as observed during the 2009 H1N1 influenza pandemic, legal, regulatory, logistical, and funding barriers slowed the ability of WHO and countries to quickly deploy or receive vaccine. Had the 2009 H1N1 influenza pandemic been more severe, the world would have been ill prepared to cope with the global demand for rapid access to medical countermeasures. This article summarizes the US government efforts to develop a national framework to deploy medical countermeasures internationally and a number of engagements to develop regional and international mechanisms, thus increasing global capacity to respond to public health emergencies.",,"['Marinissen, Maria Julia', 'Barna, Lauren', 'Meyers, Margaret', 'Sherman, Susan E.']",,,,
,PMC,History of respiratory medicine in Canada: A new Canadian Respiratory Journal series,,PMC4198226,,,,,"['Boulet, Louis-Philippe', 'Paré, Peter D']",,,,
,PMC,Antibody responses to Bordetella bronchiseptica in vaccinated and infected dogs,,PMC4137927,,,"Bordetella bronchiseptica (Bb) whole cell bacterins have been replaced with acelluar vaccines. We evaluated the response to the acellular Bb vaccines in Bb-seropositive commingled laboratory beagles and client-owned dogs with various lifestyles and vaccination histories. A single parenteral dose of the acellular Bb vaccine resulted in consistent anamnestic IgG, and to a lesser, but notable extent, IgA, Bb-reactive antibody responses in the seropositive beagles. Associated with the increase in antibodies measured by enzyme-linked immunosorbent assay (ELISA) was an increase in the complement (C)-dependent IgG antibody mediated bactericidal effect on Bb in vitro. Antibody responses in client-owned dogs were more variable and were dependent upon the vaccination history and serological evidence of previous Bb exposure. Antibodies from vaccinated dogs recognized several Bb proteins, notably P68 (pertactin) and P220 (fimbrial hemagglutinin), the response to which has been shown to be disease-sparing in Bp infections. These antibody responses were similar to those in experimentally infected dogs and in dogs that had received a widely used whole cell bacterin.",,"['Ellis, John', 'Rhodes, Carrie', 'Lacoste, Stacey', 'Krakowka, Steven']",,,,
,PMC,Novel drugs targeting Toll-like receptors for antiviral therapy,http://dx.doi.org/10.2217/fvl.14.70,PMC4303062,,,"Toll-like receptors (TLRs) are sentinel receptors of the host innate immune system that recognize conserved ‘pathogen-associated molecular patterns’ of invading microbes, including viruses. The activation of TLRs establishes antiviral innate immune responses and coordinates the development of long-lasting adaptive immunity in order to control viral pathogenesis. However, microbe-induced damage to host tissues may release ‘danger-associated molecular patterns’ that also activate TLRs, leading to an overexuberant inflammatory response and, ultimately, to tissue damage. Thus, TLRs have proven to be promising targets as therapeutics for the treatment of viral infections that result in inflammatory damage or as adjuvants in order to enhance the efficacy of vaccines. Here, we explore recent advances in TLR biology with a focus on novel drugs that target TLRs (agonists and antagonists) for antiviral therapy.",,"['Patel, Mira C', 'Shirey, Kari Ann', 'Pletneva, Lioubov M', 'Boukhvalova, Marina S', 'Garzino-Demo, Alfredo', 'Vogel, Stefanie N', 'Blanco, Jorge CG']",,,,
,PMC,Perioperative neonatal and paediatric blood transfusion,http://dx.doi.org/10.4103/0019-5049.144679,PMC4260315,25535431,CC BY-NC-SA,"Paediatric patients undergoing surgical procedures commonly require some volume of blood or blood component replacement in the perioperative period. Paediatric patients undergoing major surgery associated with substantial blood loss should be evaluated pre-operatively. Pre-operative correction of anaemia may be done considering the age, plasma volume status, clinical status and comorbidities. Maximum allowable blood loss (MABL) for surgery must be calculated, and appropriate quantity of blood and blood components should be arranged. Intraoperative monitoring of blood loss should be done, and volume of transfusion should be calculated in a protocol based manner considering the volemia and the trigger threshold for transfusion for the patient and the MABL. Early haemostasis should be achieved by judicious administration of red blood cells, blood components and pharmacological agents.",2014 Sep-Oct,"['Bharadwaj, Avnish', 'Khandelwal, Mamta', 'Bhargava, Suresh Kumar']",Indian J Anaesth,,,
,PMC,"Some serum acute phase proteins and immunoglobulins concentrations in calves with rotavirus, coronavirus, E. coli F5 and Eimeria species",,PMC4789220,,,"The purpose of this study was to evaluate the changes in the serum concentrations of haptoglobin (Hp), serum amyloid A (SAA) and IgG, IgA in calves with diarrhea caused by rotavirus, coronavirus, Escherichia coli F5 and Eimeria species. The experiment was carried out on 40 diarrhoeic and 10 non-diarrhoeic calves (group C). A total of 13 calves were infected with rotavirus or coronavirus (group V), 12 calves with E. coli F5 (group B) and 15 calves with Eimeria species (group P). SAA and Hp levels of calves in groups V, B and P were statistically higher than group C (P<0.05). SAA and Hp levels of the group B and group P were significantly higher than the group V (P<0.05). SAA and Hp levels in group B were not significantly higher than the group P. The levels of IgG and IgA were found to be lower in groups B and V compared to other groups. There was a negative correlation between immunoglobulins and the levels of serum Hp and SAA in groups B and V (r=-0.315 and r=-0.369, respectively, P<0.05). Serum SAA, Hp, IgA and IgG levels could be useful for the diagnosis and differential diagnosis of diarrhea caused by rotavirus, coronavirus, E. coli F5 and Eimeria species.",,"['Balikci, E', 'Al, M']",,,,
,PMC,"Wheezing exacerbations in early childhood: evaluation, treatment, and recent advances relevant to the genesis of asthma",http://dx.doi.org/10.1016/j.jaip.2014.06.024,PMC4190166,,,"Children who begin wheezing during early childhood are seen frequently by health care providers in primary care, in hospitals and emergency departments, and by allergists and pulmonologists. When young children, like the 2 year-old case presented here, are evaluated for wheezing, a frequent challenge for clinicians is to determine whether the symptoms represent transient, viral-induced wheezing, or whether sufficient risk factors are present to suspect that the child may experience recurrent wheezing and develop asthma. Most factors influencing prognosis are not mutually exclusive, are interrelated (i.e., cofactors), and often represent gene-environment interactions. Many of these risk factors have been, and continue to be, investigated in prospective studies in order to decipher their relative importance with the goal of developing new therapies and interventions in the future. The etiologies of wheezing in young children, diagnostic methods, treatment, prognostic factors, and potential targets for prevention of the development of asthma are discussed.",,"['Miller, E. Kathryn', 'Avila, Pedro C.', 'Khan, Yasmin W.', 'Word, Carolyn R.', 'Pelz, Barry J.', 'Papadopoulos, Nikolaos G.', 'Peebles, R. Stokes', 'Heymann, Peter W.', None]",,,,
,PMC,Classification of Emergent U.S. Strains of Porcine Epidemic Diarrhea Virus by Phylogenetic Analysis of Nucleocapsid and ORF3 Genes,http://dx.doi.org/10.1128/JCM.01708-14,PMC4313202,,,,,"['Wang, Shao', 'Cheng, Xiaoxia', 'Chen, Shilong', 'Lin, Fengqiang', 'Jiang, Bing', 'Zhu, Xiaoli', 'Li, Zhaolong', 'Wang, Jinxiang', 'Chen, Shaoying']",,,,
,PMC,Comprehensive Human Virus Screening Using High-Throughput Sequencing with a User-Friendly Representation of Bioinformatics Analysis: a Pilot Study,http://dx.doi.org/10.1128/JCM.01389-14,PMC4313162,,,"High-throughput sequencing (HTS) provides the means to analyze clinical specimens in unprecedented molecular detail. While this technology has been successfully applied to virus discovery and other related areas of research, HTS methodology has yet to be exploited for use in a clinical setting for routine diagnostics. Here, a bioinformatics pipeline (ezVIR) was designed to process HTS data from any of the standard platforms and to evaluate the entire spectrum of known human viruses at once, providing results that are easy to interpret and customizable. The pipeline works by identifying the most likely viruses present in the specimen given the sequencing data. Additionally, ezVIR can generate optional reports for strain typing, can create genome coverage histograms, and can perform cross-contamination analysis for specimens prepared in series. In this pilot study, the pipeline was challenged using HTS data from 20 clinical specimens representative of those most often collected and analyzed in daily practice. The specimens (5 cerebrospinal fluid, 7 bronchoalveolar lavage fluid, 5 plasma, 2 serum, and 1 nasopharyngeal aspirate) were originally found to be positive for a diverse range of DNA or RNA viruses by routine molecular diagnostics. The ezVIR pipeline correctly identified 14 of 14 specimens containing viruses with genomes of <40,000 bp, and 4 of 6 specimens positive for large-genome viruses. Although further validation is needed to evaluate sensitivity and to define detection cutoffs, results obtained in this pilot study indicate that the overall detection success rate, coupled with the ease of interpreting the analysis reports, makes it worth considering using HTS for clinical diagnostics.",,"['Petty, Tom J.', 'Cordey, Samuel', 'Padioleau, Ismael', 'Docquier, Mylène', 'Turin, Lara', 'Preynat-Seauve, Olivier', 'Zdobnov, Evgeny M.', 'Kaiser, Laurent']",,,,
,PMC,Reply to “Classification of Emergent U.S. Strains of Porcine Epidemic Diarrhea Virus by Phylogenetic Analysis of Nucleocapsid and ORF3 Genes”,http://dx.doi.org/10.1128/JCM.01747-14,PMC4313159,,,,,"['Zhang, Jianqiang', 'Chen, Qi', 'Gauger, Phillip C.', 'Harmon, Karen M.', 'Yoon, Kyoung-Jin']",,,,
,PMC,Technical Advance: Liposomal alendronate depletes monocytes and macrophages in the nonhuman primate model of human disease,http://dx.doi.org/10.1189/jlb.5TA0713-373R,PMC4632165,,,"Nonhuman primates are critical animal models for the study of human disorders and disease and offer a platform to assess the role of immune cells in pathogenesis via depletion of specific cellular subsets. However, this model is currently hindered by the lack of reagents that safely and specifically ablate myeloid cells of the monocyte/macrophage Lin. Given the central importance of macrophages in homeostasis and host immunity, development of a macrophage-depletion technique in nonhuman primates would open new avenues of research. Here, using LA at i.v. doses as low as 0.1 mg/kg, we show a >50% transient depletion of circulating monocytes and tissue-resident macrophages in RMs by an 11-color flow cytometric analysis. Diminution of monocytes was followed rapidly by emigration of monocytes from the bone marrow, leading to a rebound of monocytes to baseline levels. Importantly, LA was well-tolerated, as no adverse effects or changes in gross organ function were observed during depletion. These results advance the ex vivo study of myeloid cells by flow cytometry and pave the way for in vivo studies of monocyte/macrophage biology in nonhuman primate models of human disease.",,"['Burwitz, Benjamin J.', 'Reed, Jason S.', 'Hammond, Katherine B.', 'Ohme, Merete A.', 'Planer, Shannon L.', 'Legasse, Alfred W.', 'Ericsen, Adam J.', 'Richter, Yoram', 'Golomb, Gershon', 'Sacha, Jonah B.']",,,,
,PMC,Emporiatrics: The growing area of concern,,PMC4268184,25535490,CC BY-NC-SA,,2014 Sep,"Oberoi, Sukhvinder Singh",J Res Med Sci,,,
,PMC,Modulation of CD163 Expression by Metalloprotease ADAM17 Regulates Porcine Reproductive and Respiratory Syndrome Virus Entry,http://dx.doi.org/10.1128/JVI.01117-14,PMC4178901,,,"As a consequence of their effects on ectodomain shedding, members of the A disintegrin and metalloprotease (ADAM) family have been implicated in the control of various cellular processes. Although ADAM family members are also involved in cancer, inflammation, and other pathologies, it is unclear whether they affect porcine reproductive and respiratory syndrome virus (PRRSV) infection. Here, we demonstrate for the first time that inhibition of ADAM17 enhances PRRSV entry in Marc-145 and porcine alveolar macrophages (PAMs). We also demonstrate that the inhibition of ADAM17 upregulates membrane CD163 expression, a putative PRRSV receptor that is exogenously expressed in BHK-21 and endogenously expressed in Marc-145 and PAMs. Furthermore, overexpression of ADAM17 induced downregulation of CD163 expression and a reduction in PRRSV infection, whereas ablation of ADAM17 expression using specific small interfering RNA resulted in upregulation of CD163 expression with a corresponding increase in PRRSV infection. These ADAM17-mediated effects were confirmed with PRRSV nonpermissive BHK-21 cells transfected with CD163 cDNA. Overall, these findings indicate that ADAM17 downregulates CD163 expression and hinders PRRSV entry. Hence, downregulation of ADAM17 particular substrates may be an additional component of the anti-infection defenses. IMPORTANCE ADAM17 is one of the important membrane-associated metalloproteases that mediate various cellular events, as well as inflammation, cancer, and other pathologies. Here, we investigate for the first time the role of the metalloprotease ADAM17 in PRRSV infection. By using inhibitor and genetic modification methods, we demonstrate that ADAM17 negatively regulate PRRSV entry by regulating its substrate(s). More specifically, ADAM 17 mediates the downregulation of the PRRSV cellular receptor CD163. The reduction in CD163 expression represents another component of the anti-infection response initiated by ADAM17.",,"['Guo, Longjun', 'Niu, Junwei', 'Yu, Haidong', 'Gu, Weihong', 'Li, Ren', 'Luo, Xiaolei', 'Huang, Mingming', 'Tian, Zhijun', 'Feng, Li', 'Wang, Yue']",,,,
,PMC,Interferon-Induced Protein Ifit2 Protects Mice from Infection of the Peripheral Nervous System by Vesicular Stomatitis Virus,http://dx.doi.org/10.1128/JVI.01341-14,PMC4178895,,,"The interferon system provides the first line of host defense against virus infection. Mouse pathogenesis studies have revealed the importance of specific interferon-induced proteins in providing protection against specific viruses. We have previously reported that one such protein, Ifit2, protects neurons of the central nervous system from intranasal infection by the neurotropic rhabdovirus, vesicular stomatitis virus (VSV). Here, we demonstrate that Ifit2 protects the peripheral nervous system from VSV infection as well. In Ifit2(−/−) mice, VSV, injected subcutaneously into the footpad, entered the proximal lymph node, where it replicated and infected the nodal nerve endings. The infection spread to the sciatic nerve, the spinal cord, and the brain, causing paralysis. In contrast, in the wild-type mice, although VSV replicated equally well in the lymph node, infection of the sciatic nerve and the rest of the nervous system was impaired, thus preventing paralysis. Ifit2 protected only the nervous system from VSV infection; other tissues were well protected even in Ifit2(−/−) mice. These results indicate that Ifit2 is the interferon-induced protein that prevents VSV infection of neurons of both the peripheral and the central nervous systems, thus inhibiting the consequent neuropathy, but it is dispensable for protecting the cells of other tissues from VSV infection. IMPORTANCE Although viral infection is quite common, the immune system effectively protects us from viral diseases. A major part of this protection is mediated by interferon, the antiviral cytokine secreted by virus-infected cells. To empower the neighboring uninfected cells in combating the oncoming infection, interferon induces the synthesis of more than 200 new proteins, many of which have antiviral activities. The virus studied here, vesicular stomatitis virus (VSV), like its relative, rabies virus, can cause neuropathy in mice if it enters the peripheral nervous system through skin lesions; however, interferon can protect neurons from VSV infection. We have identified a specific interferon-induced protein, Ifit2, as the protein that protects neurons from VSV infection. Surprisingly, Ifit2 was not needed to protect other cell types from VSV. Our results indicate that the effector antiviral proteins of the interferon system have highly specialized functions.",,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Sen, Ganes C.']",,,,
,PMC,The Rhesus Rhadinovirus CD200 Homologue Affects Immune Responses and Viral Loads during In Vivo Infection,http://dx.doi.org/10.1128/JVI.01276-14,PMC4178886,,,"Rhesus macaque rhadinovirus (RRV) is a gammaherpesvirus of rhesus macaque (RM) monkeys that is closely related to human herpesvirus 8 (HHV-8)/Kaposi's Sarcoma-associated herpesvirus (KSHV), and it is capable of inducing diseases in simian immunodeficiency virus (SIV)-infected RM that are similar to those seen in humans coinfected with HIV and HHV-8. Both HHV-8 and RRV encode viral CD200 (vCD200) molecules that are homologues of cellular CD200, a membrane glycoprotein that regulates immune responses and helps maintain immune homeostasis via interactions with the CD200 receptor (CD200R). Though the functions of RRV and HHV-8 vCD200 molecules have been examined in vitro, the precise roles that these viral proteins play during in vivo infection remain unknown. Thus, to address the contributions of RRV vCD200 to immune regulation and disease in vivo, we generated a form of RRV that lacked expression of vCD200 for use in infection studies in RM. Our data indicated that RRV vCD200 expression limits immune responses against RRV at early times postinfection and also impacts viral loads, but it does not appear to have significant effects on disease development. Further, examination of the distribution pattern of CD200R in RM indicated that this receptor is expressed on a majority of cells in peripheral blood mononuclear cells, including B and T cells, suggesting potentially wider regulatory capabilities for both vCD200 and CD200 that are not strictly limited to myeloid lineage cells. In addition, we also demonstrate that RRV infection affects CD200R expression levels in vivo, although vCD200 expression does not play a role in this phenomenon. IMPORTANCE Cellular CD200 and its receptor, CD200R, compose a pathway that is important in regulating immune responses and is known to play a role in a variety of human diseases. A number of pathogens have been found to modulate the CD200-CD200R pathway during infection, including human herpesvirus 8 (HHV-8), the causative agent of Kaposi's sarcoma and B cell neoplasms in AIDS patients, and a closely related primate virus, rhesus macaque rhadinovirus (RRV), which infects and induces disease in rhesus macaque monkeys. HHV-8 and RRV encode homologues of CD200, termed vCD200, which are thought to play a role in preventing immune responses against these viruses. However, neither molecule has been studied in an in vivo model of infection to address their actual contributions to immunoregulation and disease. Here we report findings from our studies in which we analyzed the properties of a mutant form of RRV that lacks vCD200 expression in infected rhesus macaques.",,"['Estep, Ryan D.', 'Rawlings, Stephanie D.', 'Li, Helen', 'Manoharan, Minsha', 'Blaine, Elizabeth T.', ""O'Connor, Megan A."", 'Messaoudi, Ilhem', 'Axthelm, Michael K.', 'Wong, Scott W.']",,,,
,PMC,The P4-P2′ Amino Acids Surrounding Human Norovirus Polyprotein Cleavage Sites Define the Core Sequence Regulating Self-Processing Order,http://dx.doi.org/10.1128/JVI.01357-14,PMC4178882,,,"Noroviruses (NoV) are members of the family Caliciviridae. The human NoV open reading frame 1 (ORF1) encodes a 200-kDa polyprotein which is cleaved by the viral 20-kDa 3C-like protease (Pro, NS6) into 6 nonstructural proteins that are necessary for viral replication. The NoV ORF1 polyprotein is processed in a specific order, with “early” sites (NS1/2-3 and NS3-4) being cleaved rapidly and three “late” sites (NS4-5, NS5-6, and NS6-7) processed subsequently and less efficiently. Previously, we demonstrated that the NoV polyprotein processing order is directly correlated with the efficiency of the enzyme, which is regulated by the primary amino acid sequences surrounding ORF1 cleavage sites. Using fluorescence resonance energy transfer (FRET) peptides representing the NS2-3 and NS6-7 ORF1 cleavage sites, we now demonstrate that the amino acids spanning positions P4 to P2′ (P4-P2′) surrounding each site comprise the core sequence controlling NoV protease enzyme efficiency. Furthermore, the NoV polyprotein self-processing order can be altered by interchanging this core sequence between NS2-3 and any of the three late sites in in vitro transcription-translation assays. We also demonstrate that the nature of the side chain at the P3 position for the NS1/2-3 (Nterm/NTPase) site confers significant influence on enzyme catalysis (k(cat) and k(cat)/K(m)), a feature overlooked in previous structural studies. Molecular modeling provides possible explanations for the P3 interactions with NoV protease. IMPORTANCE Noroviruses (NoV) are the prevailing cause of nonbacterial acute gastroenteritis worldwide and pose a significant financial burden on health care systems. Proteolytic processing of the viral nonstructural polyprotein is required for norovirus replication. Previously, the core sequence of amino acids surrounding the scissile bonds responsible for governing the relative processing order had not been determined. Using both FRET-based peptides and full-length NoV polyprotein, we have successfully demonstrated that the core sequences spanning positions P4-P2′ surrounding the NS2-3, NS4-5, NS5-6, and NS6-7 cleavage sites contain all of the structural information necessary to control processing order. We also provide insight into a previously overlooked role for the NS2-3 P3 residue in enzyme efficiency. This article builds upon our previous studies on NoV protease enzymatic activities and polyprotein processing order. Our work provides significant additional insight into understanding viral polyprotein processing and has important implications for improving the design of inhibitors targeting the NoV protease.",,"['May, Jared', 'Viswanathan, Prasanth', 'Ng, Kenneth K.-S.', 'Medvedev, Alexei', 'Korba, Brent']",,,,
,PMC,Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 4 Antagonizes Beta Interferon Expression by Targeting the NF-κB Essential Modulator,http://dx.doi.org/10.1128/JVI.01396-14,PMC4178863,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly infectious pathogen that causes severe diseases in pigs and great economic losses to the swine industry worldwide. Type I interferons (IFNs) play a crucial role in antiviral immunity. In the present study, we demonstrated that infection with the highly pathogenic PRRSV strain JXwn06 antagonized type I IFN expression induced by poly(I·C) in both porcine alveolar macrophages (PAMs) and blood monocyte-derived macrophages (BMo). Subsequently, we showed that the inhibition of poly(I·C)-induced IFN-β production by PRRSV was dependent on the blocking of NF-κB signaling pathways. By screening PRRSV nonstructural and structural proteins, we demonstrated that nonstructural protein 4 (nsp4), a viral 3C-like serine protease, significantly suppressed IFN-β expression. Moreover, we verified that nsp4 inhibited NF-κB activation induced by signaling molecules, including RIG-I, VISA, TRIF, and IKKβ. nsp4 was shown to target the NF-κB essential modulator (NEMO) at the E349-S350 site to mediate its cleavage. Importantly, nsp4 mutants with defective protease activity abolished its ability to cleave NEMO and inhibit IFN-β production. These findings might have implications for our understanding of PRRSV pathogenesis and its mechanisms for evading the host immune response. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) is a major agent of respiratory diseases in pigs. Like many other viruses, PRRSV has evolved a variety of strategies to evade host antiviral innate immunity for survival and propagation. In this study, we show that PRRSV nsp4 is a novel antagonist of the NF-κB signaling pathway, which is responsible for regulating the expression of type I interferons and other crucial cytokines. We then investigated the underlying mechanism used by nsp4 to suppress NF-κB-mediated IFN-β production. We found that nsp4 interfered with the NF-κB signaling pathway through the cleavage of NEMO (a key regulator of NF-κB signaling) at the E349-S350 site, leading to the downregulation of IFN-β production induced by poly(I·C). The data presented here may help us to better understand PRRSV pathogenesis.",,"['Huang, Chen', 'Zhang, Qiong', 'Guo, Xue-kun', 'Yu, Zhi-bin', 'Xu, Ao-Tian', 'Tang, Jun', 'Feng, Wen-hai']",,,,
,PMC,Rapid Expansion of CD8(+) T Cells in Wild-Type and Type I Interferon Receptor-Deficient Mice Correlates with Protection after Low-Dose Emergency Immunization with Modified Vaccinia Virus Ankara,http://dx.doi.org/10.1128/JVI.00945-14,PMC4178859,,,"Immunization with modified vaccinia virus Ankara (MVA) can rapidly protect mice against lethal ectromelia virus (ECTV) infection, serving as an experimental model for severe systemic infections. Importantly, this early protective capacity of MVA vaccination completely depends on virus-specific cytotoxic CD8(+) T cell responses. We used MVA vaccination in the mousepox challenge model using ECTV infection to investigate the previously unknown factors required to elicit rapid protective T cell immunity in normal C57BL/6 mice and in mice lacking the interferon alpha/beta receptor (IFNAR(−/−)). We found a minimal dose of 10(5) PFU of MVA vaccine fully sufficient to allow robust protection against lethal mousepox, as assessed by the absence of disease symptoms and failure to detect ECTV in organs from vaccinated animals. Moreover, MVA immunization at low dosage also protected IFNAR(−/−) mice, indicating efficient activation of cellular immunity even in the absence of type I interferon signaling. When monitoring for virus-specific CD8(+) T cell responses in mice vaccinated with the minimal protective dose of MVA, we found significantly enhanced levels of antigen-specific T cells in animals that were MVA vaccinated and ECTV challenged compared to mice that were only vaccinated. The initial priming of naive CD8(+) T cells by MVA immunization appears to be highly efficient and, even at low doses, mediates a rapid in vivo burst of pathogen-specific T cells upon challenge. Our findings define striking requirements for protective emergency immunization against severe systemic infections with orthopoxviruses. IMPORTANCE We demonstrate that single-shot low-dose immunizations with vaccinia virus MVA can rapidly induce T cell-mediated protective immunity against lethal orthopoxvirus infections. Our data provide new evidence for an efficient protective capacity of vaccination with replication-deficient MVA. These data are of important practical relevance for public health, as the effectiveness of a safety-tested, next-generation smallpox vaccine based on MVA is still debated. Furthermore, producing sufficient amounts of vaccine is expected to be a major challenge should an outbreak occur. Moreover, prevention of other infections may require rapidly protective immunization; hence, MVA could be an extremely useful vaccine for delivering heterologous T cell antigens, particularly for infectious diseases that fit a scenario of emergency vaccination.",,"['Volz, Asisa', 'Langenmayer, Martin', 'Jany, Sylvia', 'Kalinke, Ulrich', 'Sutter, Gerd']",,,,
,PMC,H7N9 and Other Pathogenic Avian Influenza Viruses Elicit a Three-Pronged Transcriptomic Signature That Is Reminiscent of 1918 Influenza Virus and Is Associated with Lethal Outcome in Mice,http://dx.doi.org/10.1128/JVI.00570-14,PMC4178843,,,"Modulating the host response is a promising approach to treating influenza, caused by a virus whose pathogenesis is determined in part by the reaction it elicits within the host. Though the pathogenicity of emerging H7N9 influenza virus in several animal models has been reported, these studies have not included a detailed characterization of the host response following infection. Therefore, we characterized the transcriptomic response of BALB/c mice infected with H7N9 (A/Anhui/01/2013) virus and compared it to the responses induced by H5N1 (A/Vietnam/1203/2004), H7N7 (A/Netherlands/219/2003), and pandemic 2009 H1N1 (A/Mexico/4482/2009) influenza viruses. We found that responses to the H7 subtype viruses were intermediate to those elicited by H5N1 and pdm09H1N1 early in infection but that they evolved to resemble the H5N1 response as infection progressed. H5N1, H7N7, and H7N9 viruses were pathogenic in mice, and this pathogenicity correlated with increased transcription of cytokine response genes and decreased transcription of lipid metabolism and coagulation signaling genes. This three-pronged transcriptomic signature was observed in mice infected with pathogenic H1N1 strains such as the 1918 virus, indicating that it may be predictive of pathogenicity across multiple influenza virus strains. Finally, we used host transcriptomic profiling to computationally predict drugs that reverse the host response to H7N9 infection, and we identified six FDA-approved drugs that could potentially be repurposed to treat H7N9 and other pathogenic influenza viruses. IMPORTANCE Emerging avian influenza viruses are of global concern because the human population is immunologically naive to them. Current influenza drugs target viral molecules, but the high mutation rate of influenza viruses eventually leads to the development of antiviral resistance. As the host evolves far more slowly than the virus, and influenza pathogenesis is determined in part by the host response, targeting the host response is a promising approach to treating influenza. Here we characterize the host transcriptomic response to emerging H7N9 influenza virus and compare it with the responses to H7N7, H5N1, and pdm09H1N1. All three avian viruses were pathogenic in mice and elicited a transcriptomic signature that also occurs in response to the legendary 1918 influenza virus. Our work identifies host responses that could be targeted to treat severe H7N9 influenza and identifies six FDA-approved drugs that could potentially be repurposed as H7N9 influenza therapeutics.",,"['Morrison, Juliet', 'Josset, Laurence', 'Tchitchek, Nicolas', 'Chang, Jean', 'Belser, Jessica A.', 'Swayne, David E.', 'Pantin-Jackwood, Mary J.', 'Tumpey, Terrence M.', 'Katze, Michael G.']",,,,
,PMC,How Viruses Hijack the ERAD Tuning Machinery,http://dx.doi.org/10.1128/JVI.00801-14,PMC4178841,,,"An essential step during the intracellular life cycle of many positive-strand RNA viruses is the rearrangement of host cell membranes to generate membrane-bound replication platforms. For example, Nidovirales and Flaviviridae subvert the membrane of the endoplasmic reticulum (ER) for their replication. However, the absence of conventional ER and secretory pathway markers in virus-induced ER-derived membranes has for a long time hampered a thorough understanding of their biogenesis. Recent reports highlight the analogies between mouse hepatitis virus-, equine arteritis virus-, and Japanese encephalitis virus-induced replication platforms and ER-associated degradation (ERAD) tuning vesicles (or EDEMosomes) that display nonlipidated LC3 at their cytosolic face and segregate the ERAD factors EDEM1, OS-9, and SEL1L from the ER lumen. In this Gem, we briefly summarize the current knowledge on ERAD tuning pathways and how they might be hijacked for viral genome replication. As ERAD tuning components, such as SEL1L and nonlipidated LC3, appear to contribute to viral infection, these cellular pathways represent novel candidate drug targets to combat positive-strand RNA viruses.",,"['Noack, Julia', 'Bernasconi, Riccardo', 'Molinari, Maurizio']",,,,
,PMC,Unexpected Structural Features of the Hepatitis C Virus Envelope Protein 2 Ectodomain,http://dx.doi.org/10.1128/JVI.00874-14,PMC4178838,,,"Hepatitis C virus (HCV), a member of the family Flaviviridae, is a leading cause of chronic liver disease and cancer. Recent advances in HCV therapeutics have resulted in improved cure rates, but an HCV vaccine is not available and is urgently needed to control the global pandemic. Vaccine development has been hampered by the lack of high-resolution structural information for the two HCV envelope glycoproteins, E1 and E2. Recently, Kong and coworkers (Science 342:1090–1094, 2013, doi:10.1126/science.1243876) and Khan and coworkers (Nature 509[7500]:381–384, 2014, doi:10.1038/nature13117) independently determined the structure of the HCV E2 ectodomain core with some unexpected and informative results. The HCV E2 ectodomain core features a globular architecture with antiparallel β-sheets forming a central β sandwich. The residues comprising the epitopes of several neutralizing and nonneutralizing human monoclonal antibodies were also determined, which is an essential step toward obtaining a fine map of the human humoral response to HCV. Also clarified were the regions of E2 that directly bind CD81, an important HCV cellular receptor. While it has been widely assumed that HCV E2 is a class II viral fusion protein (VFP), the newly determined structure suggests that the HCV E2 ectodomain shares structural and functional similarities only with domain III of class II VFPs. The new structural determinations suggest that the HCV glycoproteins use a different mechanism than that used by class II fusion proteins for cell fusion.",,"['Sabahi, Ali', 'Uprichard, Susan L.', 'Wimley, William C.', 'Dash, Srikanta', 'Garry, Robert F.']",,,,
,PMC,Analysis of Human Rotaviruses from a Single Location Over an 18-Year Time Span Suggests that Protein Coadaption Influences Gene Constellations,http://dx.doi.org/10.1128/JVI.01562-14,PMC4136370,,,"Rotaviruses (RVs) are 11-segmented, double-stranded RNA viruses that cause severe gastroenteritis in children. In addition to an error-prone genome replication mechanism, RVs can increase their genetic diversity by reassorting genes during host coinfection. Such exchanges allow RVs to acquire advantageous genes and adapt in the face of selective pressures. However, reassortment may also impose fitness costs if it unlinks genes/proteins that have accumulated compensatory, coadaptive mutations and that operate best when kept together. To better understand human RV evolutionary dynamics, we analyzed the genome sequences of 135 strains (genotype G1/G3/G4-P[8]-I1-C1-R1-A1-N1-T1-E1-H1) that were collected at a single location in Washington, DC, during the years 1974 to 1991. Intragenotypic phylogenetic trees were constructed for each viral gene using the nucleotide sequences, thereby defining novel allele level gene constellations (GCs) and illuminating putative reassortment events. The results showed that RVs with distinct GCs cocirculated during the vast majority of the collection years and that some of these GCs persisted in the community unchanged by reassortment. To investigate the influence of protein coadaptation on GC maintenance, we performed a mutual information-based analysis of the concatenated amino acid sequences and identified an extensive covariance network. Unexpectedly, amino acid covariation was highest between VP4 and VP2, which are structural components of the RV virion that are not thought to directly interact. These results suggest that GCs may be influenced by the selective constraints placed on functionally coadapted, albeit noninteracting, viral proteins. This work raises important questions about mutation-reassortment interplay and its impact on human RV evolution. IMPORTANCE Rotaviruses are devastating human pathogens that cause severe diarrhea and kill >450,000 children each year. The virus can evolve by accumulating mutations and by acquiring new genes from other strains via a process called reassortment. However, little is known about the relationship between mutation accumulation and gene reassortment for rotaviruses and how it impacts viral evolution. In this study, we analyzed the genome sequences of human strains found in clinical fecal specimens that were collected at a single hospital over an 18-year time span. We found that many rotaviruses did not reassort their genes but instead maintained them as specific sets (i.e., constellations). By analyzing the encoded proteins, we discovered concurrent amino acid changes among them, which suggests that they are functionally coadapted to operate best when kept together. This study increases our understanding of how rotaviruses evolve over time in the human population.",,"['Zhang, Shu', 'McDonald, Paul W.', 'Thompson, Travis A.', 'Dennis, Allison F.', 'Akopov, Asmik', 'Kirkness, Ewen F.', 'Patton, John T.', 'McDonald, Sarah M.']",,,,
,PMC,Rewiring of Cellular Membrane Homeostasis by Picornaviruses,http://dx.doi.org/10.1128/JVI.00922-14,PMC4136358,,,"Viruses are obligatory intracellular parasites and utilize host elements to support key viral processes, including penetration of the plasma membrane, initiation of infection, replication, and suppression of the host's antiviral defenses. In this review, we focus on picornaviruses, a family of positive-strand RNA viruses, and discuss the mechanisms by which these viruses hijack the cellular machinery to form and operate membranous replication complexes. Studies aimed at revealing factors required for the establishment of viral replication structures identified several cellular-membrane-remodeling proteins and led to the development of models in which the virus used a preexisting cellular-membrane-shaping pathway “as is” for generating its replication organelles. However, as more data accumulate, this view is being increasingly questioned, and it is becoming clearer that viruses may utilize cellular factors in ways that are distinct from the normal functions of these proteins in uninfected cells. In addition, the proteincentric view is being supplemented by important new studies showing a previously unappreciated deep remodeling of lipid homeostasis, including extreme changes to phospholipid biosynthesis and cholesterol trafficking. The data on viral modifications of lipid biosynthetic pathways are still rudimentary, but it appears once again that the viruses may rewire existing pathways to generate novel functions. Despite remarkable progress, our understanding of how a handful of viral proteins can completely overrun the multilayered, complex mechanisms that control the membrane organization of a eukaryotic cell remains very limited.",,"['Belov, George A.', 'Sztul, Elizabeth']",,,,
,PMC,Intrinsic Innate Immunity Fails To Control Herpes Simplex Virus and Vesicular Stomatitis Virus Replication in Sensory Neurons and Fibroblasts,http://dx.doi.org/10.1128/JVI.01462-14,PMC4136337,,,"Herpes simplex virus 1 (HSV-1) establishes lifelong latent infections in the sensory neurons of the trigeminal ganglia (TG), wherein it retains the capacity to reactivate. The interferon (IFN)-driven antiviral response is critical for the control of HSV-1 acute replication. We therefore sought to further investigate this response in TG neurons cultured from adult mice deficient in a variety of IFN signaling components. Parallel experiments were also performed in fibroblasts isolated concurrently. We showed that HSV-1 replication was comparable in wild-type (WT) and IFN signaling-deficient neurons and fibroblasts. Unexpectedly, a similar pattern was observed for the IFN-sensitive vesicular stomatitis virus (VSV). Despite these findings, TG neurons responded to IFN-β pretreatment with STAT1 nuclear localization and restricted replication of both VSV and an HSV-1 strain deficient in γ34.5, while wild-type HSV-1 replication was unaffected. This was in contrast to fibroblasts in which all viruses were restricted by the addition of IFN-β. Taken together, these data show that adult TG neurons can mount an effective antiviral response only if provided with an exogenous source of IFN-β, and HSV-1 combats this response through γ34.5. These results further our understanding of the antiviral response of neurons and highlight the importance of paracrine IFN-β signaling in establishing an antiviral state. IMPORTANCE Herpes simplex virus 1 (HSV-1) is a ubiquitous virus that establishes a lifelong latent infection in neurons. Reactivation from latency can cause cold sores, blindness, and death from encephalitis. Humans with deficiencies in innate immunity have significant problems controlling HSV infections. In this study, we therefore sought to elucidate the role of neuronal innate immunity in the control of viral infection. Using neurons isolated from mice, we found that the intrinsic capacity of neurons to restrict virus replication was unaffected by the presence or absence of innate immunity. In contrast, neurons were able to mount a robust antiviral response when provided with beta interferon, a molecule that strongly stimulates innate immunity, and that HSV-1 can combat this response through the γ34.5 viral gene. Our results have important implications for understanding how the nervous system defends itself against virus infections.",,"['Rosato, Pamela C.', 'Leib, David A.']",,,,
,PMC,Defining the Chemokine Basis for Leukocyte Recruitment during Viral Encephalitis,http://dx.doi.org/10.1128/JVI.03421-13,PMC4136330,,,"The encephalitic response to viral infection requires local chemokine production and the ensuing recruitment of immune and inflammatory leukocytes. Accordingly, chemokine receptors present themselves as plausible therapeutic targets for drugs aimed at limiting encephalitic responses. However, it remains unclear which chemokines are central to this process and whether leukocyte recruitment is important for limiting viral proliferation and survival in the brain or whether it is predominantly a driver of coincident inflammatory pathogenesis. Here we examine chemokine expression and leukocyte recruitment in the context of avirulent and virulent Semliki Forest virus (SFV) as well as West Nile virus infection and demonstrate rapid and robust expression of a variety of inflammatory CC and CXC chemokines in all models. On this basis, we define a chemokine axis involved in leukocyte recruitment to the encephalitic brain during SFV infection. CXCR3 is the most active; CCR2 is also active but less so, and CCR5 plays only a modest role in leukocyte recruitment. Importantly, inhibition of each of these receptors individually and the resulting suppression of leukocyte recruitment to the infected brain have no effect on viral titer or survival following infection with a virulent SFV strain. In contrast, simultaneous blockade of CXCR3 and CCR2 results in significantly reduced mortality in response to virulent SFV infection. In summary, therefore, our data provide an unprecedented level of insight into chemokine orchestration of leukocyte recruitment in viral encephalitis. Our data also highlight CXCR3 and CCR2 as possible therapeutic targets for limiting inflammatory damage in response to viral infection of the brain. IMPORTANCE Brain inflammation (encephalitis) in response to viral infection can lead to severe illness and even death. This therefore represents an important clinical problem and one that requires the development of new therapeutic approaches. Central to the pathogenesis of encephalitis is the recruitment of inflammatory leukocytes to the infected brain, a process driven by members of the chemokine family. Here we provide an in-depth analysis of the chemokines involved in leukocyte recruitment to the virally infected brain and demonstrate that simultaneous blockade of two of these receptors, namely, CXCR3 and CCR2, does not alter viral titers within the brain but markedly reduces inflammatory leukocyte recruitment and enhances survival in a murine model of lethal viral encephalitis. Our results therefore highlight chemokine receptors as plausible therapeutic targets in treating viral encephalitis.",,"['Michlmayr, Daniela', 'McKimmie, Clive S.', 'Pingen, Marieke', 'Haxton, Ben', 'Mansfield, Karen', 'Johnson, Nicholas', 'Fooks, Anthony R.', 'Graham, Gerard J.']",,,,
,PMC,"Verdinexor, a Novel Selective Inhibitor of Nuclear Export, Reduces Influenza A Virus Replication In Vitro and In Vivo",http://dx.doi.org/10.1128/JVI.01774-14,PMC4136318,,,"Influenza is a global health concern, causing death, morbidity, and economic losses. Chemotherapeutics that target influenza virus are available; however, rapid emergence of drug-resistant strains is common. Therapeutic targeting of host proteins hijacked by influenza virus to facilitate replication is an antiviral strategy to reduce the development of drug resistance. Nuclear export of influenza virus ribonucleoprotein (vRNP) from infected cells has been shown to be mediated by exportin 1 (XPO1) interaction with viral nuclear export protein tethered to vRNP. RNA interference screening has identified XPO1 as a host proinfluenza factor where XPO1 silencing results in reduced influenza virus replication. The Streptomyces metabolite XPO1 inhibitor leptomycin B (LMB) has been shown to limit influenza virus replication in vitro; however, LMB is toxic in vivo, which makes it unsuitable for therapeutic use. In this study, we tested the anti-influenza virus activity of a new class of orally available small-molecule selective inhibitors of nuclear export, specifically, the XPO1 antagonist KPT-335 (verdinexor). Verdinexor was shown to potently and selectively inhibit vRNP export and effectively inhibited the replication of various influenza virus A and B strains in vitro, including pandemic H1N1 virus, highly pathogenic H5N1 avian influenza virus, and the recently emerged H7N9 strain. In vivo, prophylactic and therapeutic administration of verdinexor protected mice against disease pathology following a challenge with influenza virus A/California/04/09 or A/Philippines/2/82-X79, as well as reduced lung viral loads and proinflammatory cytokine expression, while having minimal toxicity. These studies show that verdinexor acts as a novel anti-influenza virus therapeutic agent. IMPORTANCE Antiviral drugs represent important means of influenza virus control. However, substantial resistance to currently approved influenza therapeutic drugs has developed. New antiviral approaches are required to address drug resistance and reduce the burden of influenza virus-related disease. This study addressed critical preclinical studies for the development of verdinexor (KPT-335) as a novel antiviral drug. Verdinexor blocks progeny influenza virus genome nuclear export, thus effectively inhibiting virus replication. Verdinexor was found to limit the replication of various strains of influenza A and B viruses, including a pandemic H1N1 influenza virus strain, a highly pathogenic H5N1 avian influenza virus strain, and a recently emerging H7N9 influenza virus strain. Importantly, oral verdinexor treatments, given prophylactically or therapeutically, were efficacious in limiting lung virus burdens in influenza virus-infected mice, in addition to limiting lung proinflammatory cytokine expression, pathology, and death. Thus, this study demonstrated that verdinexor is efficacious against influenza virus infection in vitro and in vivo.",,"['Perwitasari, Olivia', 'Johnson, Scott', 'Yan, Xiuzhen', 'Howerth, Elizabeth', 'Shacham, Sharon', 'Landesman, Yosef', 'Baloglu, Erkan', 'McCauley, Dilara', 'Tamir, Sharon', 'Tompkins, S. Mark', 'Tripp, Ralph A.']",,,,
,PMC,Ebola Virus Modulates Transforming Growth Factor β Signaling and Cellular Markers of Mesenchyme-Like Transition in Hepatocytes,http://dx.doi.org/10.1128/JVI.01410-14,PMC4136307,,,"Ebola virus (EBOV) causes a severe hemorrhagic disease in humans and nonhuman primates, with a median case fatality rate of 78.4%. Although EBOV is considered a public health concern, there is a relative paucity of information regarding the modulation of the functional host response during infection. We employed temporal kinome analysis to investigate the relative early, intermediate, and late host kinome responses to EBOV infection in human hepatocytes. Pathway overrepresentation analysis and functional network analysis of kinome data revealed that transforming growth factor (TGF-β)-mediated signaling responses were temporally modulated in response to EBOV infection. Upregulation of TGF-β signaling in the kinome data sets correlated with the upregulation of TGF-β secretion from EBOV-infected cells. Kinase inhibitors targeting TGF-β signaling, or additional cell receptors and downstream signaling pathway intermediates identified from our kinome analysis, also inhibited EBOV replication. Further, the inhibition of select cell signaling intermediates identified from our kinome analysis provided partial protection in a lethal model of EBOV infection. To gain perspective on the cellular consequence of TGF-β signaling modulation during EBOV infection, we assessed cellular markers associated with upregulation of TGF-β signaling. We observed upregulation of matrix metalloproteinase 9, N-cadherin, and fibronectin expression with concomitant reductions in the expression of E-cadherin and claudin-1, responses that are standard characteristics of an epithelium-to-mesenchyme-like transition. Additionally, we identified phosphorylation events downstream of TGF-β that may contribute to this process. From these observations, we propose a model for a broader role of TGF-β-mediated signaling responses in the pathogenesis of Ebola virus disease. IMPORTANCE Ebola virus (EBOV), formerly Zaire ebolavirus, causes a severe hemorrhagic disease in humans and nonhuman primates and is the most lethal Ebola virus species, with case fatality rates of up to 90%. Although EBOV is considered a worldwide concern, many questions remain regarding EBOV molecular pathogenesis. As it is appreciated that many cellular processes are regulated through kinase-mediated phosphorylation events, we employed temporal kinome analysis to investigate the functional responses of human hepatocytes to EBOV infection. Administration of kinase inhibitors targeting signaling pathway intermediates identified in our kinome analysis inhibited viral replication in vitro and reduced EBOV pathogenesis in vivo. Further analysis of our data also demonstrated that EBOV infection modulated TGF-β-mediated signaling responses and promoted “mesenchyme-like” phenotypic changes. Taken together, these results demonstrated that EBOV infection specifically modulates TGF-β-mediated signaling responses in epithelial cells and may have broader implications in EBOV pathogenesis.",,"['Kindrachuk, Jason', 'Wahl-Jensen, Victoria', 'Safronetz, David', 'Trost, Brett', 'Hoenen, Thomas', 'Arsenault, Ryan', 'Feldmann, Friederike', 'Traynor, Dawn', 'Postnikova, Elena', 'Kusalik, Anthony', 'Napper, Scott', 'Blaney, Joseph E.', 'Feldmann, Heinz', 'Jahrling, Peter B.']",,,,
,PMC,"Newcastle Disease Virus Vector Producing Human Norovirus-Like Particles Induces Serum, Cellular, and Mucosal Immune Responses in Mice",http://dx.doi.org/10.1128/JVI.01570-14,PMC4136303,,,"Human norovirus infection is the most common cause of viral gastroenteritis worldwide. Development of an effective vaccine is required for reducing norovirus outbreaks. The inability to grow human norovirus in cell culture has hindered the development of live-attenuated vaccines. To overcome this obstacle, we generated a recombinant Newcastle disease virus (rNDV)-vectored experimental norovirus vaccine by expressing the capsid protein (VP1) of norovirus strain VA387. We compared two different NDV vectors, a conventional rNDV vector and a modified rNDV vector, for their efficiencies in expressing VP1 protein. Our results showed that the modified vector replicated to higher titers and expressed higher levels of VP1 protein in DF1 cells and in allantoic fluid of embryonated chicken eggs than did the conventional vector. We further demonstrated that the VP1 protein produced by rNDVs was able to self-assemble into virus-like particles (VLPs) that are morphologically similar to baculovirus-expressed VLPs. Evaluation of their immunogenicity in mice showed that the modified rNDV vector induced a higher level of IgG response than those induced by the conventional vector and by the baculovirus-expressed VLPs. The rNDV vectors predominantly induced IgG2a subclass antibody for the Th1 response, and specifically, high levels of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-2 (IL-2) were detected in splenocytes. In addition, the modified rNDV vector induced a higher level of fecal IgA response in mice than did baculovirus-expressed VLPs. Our findings suggest that the rNDV vector is an efficient system to produce cost-effective VLPs in embryonated chicken eggs and has the potential to be used as a live-attenuated vaccine in humans. IMPORTANCE Noroviruses are the major cause of viral gastroenteritis worldwide. Currently, effective vaccines against norovirus infection are not available. In this study, we have evaluated Newcastle disease virus (NDV) as a vaccine vector for norovirus. Our results suggest that NDV can be used not only as a cost-effective method for large-scale production of norovirus-like particle vaccines but also as a live-attenuated vectored vaccine.",,"['Kim, Shin-Hee', 'Chen, Shun', 'Jiang, Xi', 'Green, Kim Y.', 'Samal, Siba K.']",,,,
,PMC,Isolation and Characterization of a Novel Alphaherpesvirus in Fruit Bats,http://dx.doi.org/10.1128/JVI.01277-14,PMC4136302,,,"Bats are known to harbor emerging RNA viruses. Recent studies have used high-throughput sequencing technology to identify various virus species, including DNA viruses that are harbored by bats; however, little is known about the nature of these potentially novel viruses. Here, we report the characterization of a novel herpesvirus isolated from an Indonesian pteropodid bat. The virus, tentatively named fruit bat alphaherpesvirus 1 (FBAHV1), has a double-stranded DNA genome of 149,459 bp. The phylogenetic analyses suggested that FBAHV1 is phylogenetically grouped with simplexviruses within the subfamily Alphaherpesvirinae. Inoculation of FBAHV1 into laboratory mice caused a lethal infection. Virus infection was observed in lung, liver, and brain tissue. Serological and PCR screening revealed that fruit bats infected with FBAHV1 or its related virus are widely distributed in Indonesia. The identification of FBAHV1 makes a considerable contribution to our understanding of simplexviruses associated with bats. IMPORTANCE Bats are known to harbor emerging viruses, such as lyssaviruses, henipaviruses, severe acute respiratory syndrome-like coronaviruses, and filoviruses. Although alphaherpesviruses are disseminated in humans and other animals, there is little information about their distribution in bats. Here, we isolated a previously unknown alphaherpesvirus from an Indonesian fruit bat. Genome sequence analysis suggested that the virus is a member of the genus Simplexvirus within the subfamily Alphaherpesvirinae, which also includes common human viruses, such as herpes simplex virus 1 and herpes simplex virus 2. FBAHV1 is the first bat-derived alphaherpesvirus whose complete genome has been sequenced.",,"['Sasaki, Michihito', 'Setiyono, Agus', 'Handharyani, Ekowati', 'Kobayashi, Shintaro', 'Rahmadani, Ibenu', 'Taha, Siswatiana', 'Adiani, Sri', 'Subangkit, Mawar', 'Nakamura, Ichiro', 'Sawa, Hirofumi', 'Kimura, Takashi']",,,,
,PMC,Picornavirus Morphogenesis,http://dx.doi.org/10.1128/MMBR.00012-14,PMC4187686,,,"SUMMARY: The Picornaviridae represent a large family of small plus-strand RNA viruses that cause a bewildering array of important human and animal diseases. Morphogenesis is the least-understood step in the life cycle of these viruses, and this process is difficult to study because encapsidation is tightly coupled to genome translation and RNA replication. Although the basic steps of assembly have been known for some time, very few details are available about the mechanism and factors that regulate this process. Most of the information available has been derived from studies of enteroviruses, in particular poliovirus, where recent evidence has shown that, surprisingly, the specificity of encapsidation is governed by a viral protein-protein interaction that does not involve an RNA packaging signal. In this review, we make an attempt to summarize what is currently known about the following topics: (i) encapsidation intermediates, (ii) the specificity of encapsidation (iii), viral and cellular factors that are required for encapsidation, (iv) inhibitors of encapsidation, and (v) a model of enterovirus encapsidation. Finally, we compare some features of picornavirus morphogenesis with those of other plus-strand RNA viruses.",,"['Jiang, Ping', 'Liu, Ying', 'Ma, Hsin-Chieh', 'Paul, Aniko V.', 'Wimmer, Eckard']",,,,
,PMC,Microbial Peptidyl-Prolyl cis/trans Isomerases (PPIases): Virulence Factors and Potential Alternative Drug Targets,http://dx.doi.org/10.1128/MMBR.00015-14,PMC4187684,,,"SUMMARY: Initially discovered in the context of immunomodulation, peptidyl-prolyl cis/trans isomerases (PPIases) were soon identified as enzymes catalyzing the rate-limiting protein folding step at peptidyl bonds preceding proline residues. Intense searches revealed that PPIases are a superfamily of proteins consisting of three structurally distinguishable families with representatives in every described species of prokaryote and eukaryote and, recently, even in some giant viruses. Despite the clear-cut enzymatic activity and ubiquitous distribution of PPIases, reports on solely PPIase-dependent biological roles remain scarce. Nevertheless, they have been found to be involved in a plethora of biological processes, such as gene expression, signal transduction, protein secretion, development, and tissue regeneration, underscoring their general importance. Hence, it is not surprising that PPIases have also been identified as virulence-associated proteins. The extent of contribution to virulence is highly variable and dependent on the pleiotropic roles of a single PPIase in the respective pathogen. The main objective of this review is to discuss this variety in virulence-related bacterial and protozoan PPIases as well as the involvement of host PPIases in infectious processes. Moreover, a special focus is given to Legionella pneumophila macrophage infectivity potentiator (Mip) and Mip-like PPIases of other pathogens, as the best-characterized virulence-related representatives of this family. Finally, the potential of PPIases as alternative drug targets and first tangible results are highlighted.",,"['Ünal, Can M.', 'Steinert, Michael']",,,,
,PMC,MERS-CoV,http://dx.doi.org/10.5001/omj.2014.102,PMC4202221,,,,,"['Joob, Beuy', 'Wiwanitkit, Viroj']",,,,
,PMC,A remarkably stable kissing-loop interaction defines substrate recognition by the Neurospora Varkud Satellite ribozyme,http://dx.doi.org/10.1261/rna.046144.114,PMC4138328,,,"Kissing loops are tertiary structure elements that often play key roles in functional RNAs. In the Neurospora VS ribozyme, a kissing-loop interaction between the stem–loop I (SLI) substrate and stem–loop V (SLV) of the catalytic domain is known to play an important role in substrate recognition. In addition, this I/V kissing-loop interaction is associated with a helix shift in SLI that activates the substrate for catalysis. To better understand the role of this kissing-loop interaction in substrate recognition and activation by the VS ribozyme, we performed a thermodynamic characterization by isothermal titration calorimetry using isolated SLI and SLV stem–loops. We demonstrate that preshifted SLI variants have higher affinity for SLV than shiftable SLI variants, with an energetic cost of 1.8–3 kcal/mol for the helix shift in SLI. The affinity of the preshifted SLI for SLV is remarkably high, the interaction being more stable by 7–8 kcal/mol than predicted for a comparable duplex containing three Watson–Crick base pairs. The structural basis of this remarkable stability is discussed in light of previous NMR studies. Comparative thermodynamic studies reveal that kissing-loop complexes containing 6–7 Watson–Crick base pairs are as stable as predicted from comparable RNA duplexes; however, those with 2–3 Watson–Crick base pairs are more stable than predicted. Interestingly, the stability of SLI/ribozyme complexes is similar to that of SLI/SLV complexes. Thus, the I/V kissing loop interaction represents the predominant energetic contribution to substrate recognition by the trans-cleaving VS ribozyme.",,"['Bouchard, Patricia', 'Legault, Pascale']",,,,
,PMC,"Authors’ reply. MERS-CoV, surgical mask and N95 respirators",http://dx.doi.org/10.11622/smedj.2014125,PMC4293956,,,,,"['Chung, Jasmine Shimin', 'Ling, Moi Lin', 'Seto, Wing Hong', 'Ang, Brenda Sze Peng', 'Tambyah, Paul Anantharajah']",,,,
,PMC,"MERS-CoV, surgical mask and N95 respirators",http://dx.doi.org/10.11622/smedj.2014124,PMC4293953,,,,,"Wiwanitkit, Viroj",,,,
,PMC,Chronic obstructive pulmonary disease exacerbations: latest evidence and clinical implications,http://dx.doi.org/10.1177/2040622314532862,PMC4131503,,,Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. The natural history of COPD is punctuated by exacerbations which have major short- and long-term implications on the patient and healthcare system. Evidence-based guidelines stipulate that early detection and prompt treatment of exacerbations are essential to ensure optimal outcomes and to reduce the burden of COPD. Several factors can identify populations at risk of exacerbations. Implementing prevention measures in patients at risk is a major goal in the management of COPD.,,"['Qureshi, Hammad', 'Sharafkhaneh, Amir', 'Hanania, Nicola A.']",,,,
,PMC,Luciferase Immunoprecipitation Systems for Measuring Antibodies in Autoimmune and Infectious Diseases,http://dx.doi.org/10.1016/j.trsl.2014.08.006,PMC4306608,,,"Antibody profiles have the potential to revolutionize personalized medicine by providing important information related to autoimmunity against self-proteins and exposure to infectious agents. One immunoassay technology, Luciferase Immunoprecipitation Systems (LIPS), harnesses light emitting recombinant proteins to generate robust, high quality antibody data often spanning a large dynamic range of detection. Here we describe the general format of LIPS and discuss studies using the technology to measure autoantibodies in several human autoimmune diseases including type I diabetes, Sjögren's syndrome, systemic lupus erythematosus, and immunodeficiencies secondary to anti-cytokine autoantibodies. We also describe the usefulness of evaluating antibodies against single or multiple antigens from infectious agents for diagnosis, pathogen discovery and for obtaining individual exposure profiles. These diverse findings support the notion that LIPS is a useful technology for generating antibody profiles for personalized diagnosis and monitoring of human health.",,"['Burbelo, Peter D.', 'Lebovitz, Evan E.', 'Notkins, Abner L.']",,,,
,PMC,Antibiotic prescribing for upper respiratory tract infections in the Asia-Pacific region: A brief review,,PMC4399404,,,"This review highlights the high prevalence of antibiotic use for upper respiratory tract infections (URTIs) in a larger part of the Asia-Pacific region. Since URTIs are one of the common reasons for primary care consultations in this region, inappropriate use of antibiotic in both quantity and drug choice has greatly influenced the development of antibiotic resistance. Notwithstanding the paucity of Asia-Pacific data on the above issues, the available information suggests urgent actions needed to be taken to promote judicious antibiotic use at the point-of-care through a multi-pronged approach targeting the patients/consumers (or parents), healthcare providers and health care systems.",,"Teng, CL",,,,
,PMC,"The effectiveness of seasonal trivalent inactivated influenza vaccine in preventing influenza hospitalisations and primary care visits in Auckland, New Zealand in 2013: provisional results",,PMC4627593,,,We present provisional estimates of influenza vaccine effectiveness (VE) for the NZ 2013 season. A case test-negative study was used to estimate propensity adjusted vaccine effectiveness. Influenza vaccination provided 52% (95% confidence interval (CI): 27% to 68%) protection against laboratory-confirmed influenza hospitalisation and 53% (95% CI: 28% to 70%) against laboratory-confirmed influenza in patients presenting to general practice.,,"['Turner, Nikki', 'Pierse, Nevil', 'Bissielo, Ange', 'Huang, Q Sue', 'Radke, Sarah', 'Baker, Michael', 'Widdowson, Marc-Alain', 'Kelly, Heath']",,,,
,PMC,"Viral etiology of mumps-like illnesses in suspected mumps cases reported in Catalonia, Spain",http://dx.doi.org/10.4161/hv.36165,PMC4514168,,,"We investigated the etiology of reported sporadic suspected mumps cases with a negative RT-PCR result for the mumps virus in the Barcelona-South region in 2007–2011. Samples from mumps virus-negative patients presenting unilateral or bilateral parotitis or other salivary gland swelling were tested for Epstein-Barr virus (EBV) by real-time PCR and for respiratory viruses by two multiplex-PCR-based assays to detect parainfluenza virus (PIV) 1–4, influenza virus (InV) A, B and C, respiratory syncytial virus (RSV), enterovirus, coronavirus 229E, coronavirus OC43, and rhinovirus. 101 samples were analyzed in persons aged 8 months to 50 years. Oral samples were collected on the first day of glandular swelling in 53 patients (52.5%), and on the first two days in 74 patients (73.3%). Viruses were detected in 52 (51.5%) of samples: one virus (25 EBV, 8 PIV3, 4 adenovirus, 4 PIV2, 1 PIV1, 1 InVA, and 1 enterovirus) was detected in 44 patients (84.6%), two viruses in 7 patients, and three viruses in one patient. In 58 patients (57.5%) whose sample was collected in the first 2 days after onset of parotitis and had received two doses of MMR vaccine and in 15 patients (14.8%) whose sample was collected on the first day, it is very likely that the cause was not the mumps virus. This would mean that 72.3% (73/101) of the reported sporadic suspected mumps cases were not mumps cases. The timing of oral-sample collection is crucial to correctly interpret the negative results for mumps virus RNA, especially when suspected cases occur in vaccinated persons.",,"['Barrabeig, Irene', 'Costa, Josep', 'Rovira, Ariadna', 'Marcos, M Angeles', 'Isanta, Ricard', 'López-Adalid, Rubén', 'Cervilla, Ana', 'Torner, Nuria', 'Domínguez, Angela']",,,,
,PMC,Nonlytic viral spread enhanced by autophagy components,http://dx.doi.org/10.1073/pnas.1401437111,PMC4246951,,,"The cell-to-cell spread of cytoplasmic constituents such as nonenveloped viruses and aggregated proteins is usually thought to require cell lysis. However, mechanisms of unconventional secretion have been described that bypass the secretory pathway for the extracellular delivery of cytoplasmic molecules. Components of the autophagy pathway, an intracellular recycling process, have been shown to play a role in the unconventional secretion of cytoplasmic signaling proteins. Poliovirus is a lytic virus, although a few examples of apparently nonlytic spread have been documented. Real demonstration of nonlytic spread for poliovirus or any other cytoplasmic constituent thought to exit cells via unconventional secretion requires demonstration that a small amount of cell lysis in the cellular population is not responsible for the release of cytosolic material. Here, we use quantitative time-lapse microscopy to show the spread of infectious cytoplasmic material between cells in the absence of lysis. siRNA-mediated depletion of autophagy protein LC3 reduced nonlytic intercellular viral transfer. Conversely, pharmacological stimulation of the autophagy pathway caused more rapid viral spread in tissue culture and greater pathogenicity in mice. Thus, the unconventional secretion of infectious material in the absence of cell lysis is enabled by components of the autophagy pathway. It is likely that other nonenveloped viruses also use this pathway for nonlytic intercellular spread to affect pathogenesis in infected hosts.",,"['Bird, Sara Whitney', 'Maynard, Nathaniel D.', 'Covert, Markus W.', 'Kirkegaard, Karla']",,,,
,PMC,Diversity and clonal selection in the human T-cell repertoire,http://dx.doi.org/10.1073/pnas.1409155111,PMC4246948,,,"T-cell receptor (TCR) diversity, a prerequisite for immune system recognition of the universe of foreign antigens, is generated in the first two decades of life in the thymus and then persists to an unknown extent through life via homeostatic proliferation of naïve T cells. We have used next-generation sequencing and nonparametric statistical analysis to estimate a lower bound for the total number of different TCR beta (TCRB) sequences in human repertoires. We arrived at surprisingly high minimal estimates of 100 million unique TCRB sequences in naïve CD4 and CD8 T-cell repertoires of young adults. Naïve repertoire richness modestly declined two- to fivefold in healthy elderly. Repertoire richness contraction with age was even less pronounced for memory CD4 and CD8 T cells. In contrast, age had a major impact on the inequality of clonal sizes, as estimated by a modified Gini–Simpson index clonality score. In particular, large naïve T-cell clones that were distinct from memory clones were found in the repertoires of elderly individuals, indicating uneven homeostatic proliferation without development of a memory cell phenotype. Our results suggest that a highly diverse repertoire is maintained despite thymic involution; however, peripheral fitness selection of T cells leads to repertoire perturbations that can influence the immune response in the elderly.",,"['Qi, Qian', 'Liu, Yi', 'Cheng, Yong', 'Glanville, Jacob', 'Zhang, David', 'Lee, Ji-Yeun', 'Olshen, Richard A.', 'Weyand, Cornelia M.', 'Boyd, Scott D.', 'Goronzy, Jörg J.']",,,,
,PMC,Evacuation of the ICU: Care of the Critically Ill and Injured During Pandemics and Disasters: CHEST Consensus Statement,http://dx.doi.org/10.1378/chest.14-0735,PMC4504249,,,"BACKGROUND: Despite the high risk for patient harm during unanticipated ICU evacuations, critical care providers receive little to no training on how to perform safe and effective ICU evacuations. We reviewed the pertinent published literature and offer suggestions for the critical care provider regarding ICU evacuation. The suggestions in this article are important for all who are involved in pandemics or disasters with multiple critically ill or injured patients, including front-line clinicians, hospital administrators, and public health or government officials. METHODS: The Evacuation and Mobilization topic panel used the American College of Chest Physicians (CHEST) Guidelines Oversight Committee’s methodology to develop seven key questions for which specific literature searches were conducted to identify studies upon which evidence-based recommendations could be made. No studies of sufficient quality were identified. Therefore, the panel developed expert opinion-based suggestions using a modified Delphi process. RESULTS: Based on current best evidence, we provide 13 suggestions outlining a systematic approach to prepare for and execute an effective ICU evacuation during a disaster. Interhospital and intrahospital collaboration and functional ICU communication are critical for success. Pre-event planning and preparation are required for a no-notice evacuation. A Critical Care Team Leader must be designated within the Hospital Incident Command System. A three-stage ICU Evacuation Timeline, including (1) no immediate threat, (2) evacuation threat, and (3) evacuation implementation, should be used. Detailed suggestions on ICU evacuation, including regional planning, evacuation drills, patient transport preparation and equipment, patient prioritization and distribution for evacuation, patient information and tracking, and federal and international evacuation assistance systems, are also provided. CONCLUSIONS: Successful ICU evacuation during a disaster requires active preparation, participation, communication, and leadership by critical care providers. Critical care providers have a professional obligation to become better educated, prepared, and engaged with the processes of ICU evacuation to provide a safe continuum of critical care during a disaster.",,"['King, Mary A.', 'Niven, Alexander S.', 'Beninati, William', 'Fang, Ray', 'Einav, Sharon', 'Rubinson, Lewis', 'Kissoon, Niranjan', 'Devereaux, Asha V.', 'Christian, Michael D.', 'Grissom, Colin K.', None]",,,,
,PMC,Engagement and Education: Care of the Critically Ill and Injured During Pandemics and Disasters: CHEST Consensus Statement,http://dx.doi.org/10.1378/chest.14-0740,PMC4504247,,,"BACKGROUND: Engagement and education of ICU clinicians in disaster preparedness is fragmented by time constraints and institutional barriers and frequently occurs during a disaster. We reviewed the existing literature from 2007 to April 2013 and expert opinions about clinician engagement and education for critical care during a pandemic or disaster and offer suggestions for integrating ICU clinicians into planning and response. The suggestions in this article are important for all of those involved in a pandemic or large-scale disaster with multiple critically ill or injured patients, including front-line clinicians, hospital administrators, and public health or government officials. METHODS: A systematic literature review was performed and suggestions formulated according to the American College of Chest Physicians (CHEST) Consensus Statement development methodology. We assessed articles, documents, reports, and gray literature reported since 2007. Following expert-informed sorting and review of the literature, key priority areas and questions were developed. No studies of sufficient quality were identified upon which to make evidence-based recommendations. Therefore, the panel developed expert opinion-based suggestions using a modified Delphi process. RESULTS: Twenty-three suggestions were formulated based on literature-informed consensus opinion. These suggestions are grouped according to the following thematic elements: (1) situational awareness, (2) clinician roles and responsibilities, (3) education, and (4) community engagement. Together, these four elements are considered to form the basis for effective ICU clinician engagement for mass critical care. CONCLUSIONS: The optimal engagement of the ICU clinical team in caring for large numbers of critically ill patients due to a pandemic or disaster will require a departure from the routine independent systems operating in hospitals. An effective response will require robust information systems; coordination among clinicians, hospitals, and governmental organizations; pre-event engagement of relevant stakeholders; and standardized core competencies for the education and training of critical care clinicians.",,"['Devereaux, Asha V.', 'Tosh, Pritish K.', 'Hick, John L.', 'Hanfling, Dan', 'Geiling, James', 'Reed, Mary Jane', 'Uyeki, Timothy M.', 'Shah, Umair A.', 'Fagbuyi, Daniel B.', 'Skippen, Peter', 'Dichter, Jeffrey R.', 'Kissoon, Niranjan', 'Christian, Michael D.', 'Upperman, Jeffrey S.', None]",,,,
,PMC,Changing Faces in Virology: The Dutch Shift from Oncogenic to Oncolytic Viruses,http://dx.doi.org/10.1089/hum.2014.092,PMC4180303,,,"Viruses have two opposing faces. On the one hand, they can cause harm and disease. A virus may manifest directly as a contagious disease with a clinical pathology of varying significance. A viral infection can also have delayed consequences, and in rare cases may cause cellular transformation and cancer. On the other hand, viruses may provide hope: hope for an efficacious treatment of serious disease. Examples of the latter are the use of viruses as a vaccine, as transfer vector for therapeutic genes in a gene therapy setting, or, more directly, as therapeutic anticancer agent in an oncolytic-virus therapy setting. Already there is evidence for antitumor activity of oncolytic viruses. The antitumor efficacy seems linked to their capacity to induce a tumor-directed immune response. Here, we will provide an overview on the development of oncolytic viruses and their clinical evaluation from the Dutch perspective.",,"['Belcaid, Zineb', 'Lamfers, Martine L.M.', 'van Beusechem, Victor W.', 'Hoeben, Rob C.']",,,,
,PMC,The Cellular Redox Environment Alters Antigen Presentation,http://dx.doi.org/10.1074/jbc.M114.573402,PMC4183829,,,"Cysteine-containing peptides represent an important class of T cell epitopes, yet their prevalence remains underestimated. We have established and interrogated a database of around 70,000 naturally processed MHC-bound peptides and demonstrate that cysteine-containing peptides are presented on the surface of cells in an MHC allomorph-dependent manner and comprise on average 5–10% of the immunopeptidome. A significant proportion of these peptides are oxidatively modified, most commonly through covalent linkage with the antioxidant glutathione. Unlike some of the previously reported cysteine-based modifications, this represents a true physiological alteration of cysteine residues. Furthermore, our results suggest that alterations in the cellular redox state induced by viral infection are communicated to the immune system through the presentation of S-glutathionylated viral peptides, resulting in altered T cell recognition. Our data provide a structural basis for how the glutathione modification alters recognition by virus-specific T cells. Collectively, these results suggest that oxidative stress represents a mechanism for modulating the virus-specific T cell response.",,"['Trujillo, Jonathan A.', 'Croft, Nathan P.', 'Dudek, Nadine L.', 'Channappanavar, Rudragouda', 'Theodossis, Alex', 'Webb, Andrew I.', 'Dunstone, Michelle A.', 'Illing, Patricia T.', 'Butler, Noah S.', 'Fett, Craig', 'Tscharke, David C.', 'Rossjohn, Jamie', 'Perlman, Stanley', 'Purcell, Anthony W.']",,,,
,PMC,SARS-CoV ORF-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome,http://dx.doi.org/10.4049/jimmunol.1303196,PMC4179872,,,"Coronaviruses (CoV) have recently emerged as potentially serious pathogens that can cause significant human morbidity and death. The severe acute respiratory syndrome (SARS)-CoV was identified as the etiologic agent of the 2002-3 international SARS outbreak. Yet how SARS evades innate immune responses to cause human disease remains poorly understood. Here, we show that a protein encoded by SARS-CoV designated as open reading frame-9b (ORF-9b) localizes to mitochondria and causes mitochondrial elongation by triggering ubiquitination and proteasomal degradation of dynamin-like protein (DRP1), a host protein involved in mitochondrial fission. Also, acting on mitochondria ORF-9b targets the mitochondrial-associated adaptor molecule MAVS signalosome by usurping poly(C)-binding protein 2 (PCBP2) and the HECT domain E3 ligase AIP4 to trigger the degradation of MAVS, TRAF3, and TRAF6. This severely limits host cell interferon responses. Reducing either PCBP2 or AIP4 expression substantially reversed the ORF-9b mediated reduction of MAVS and the suppression of anti-viral transcriptional responses. Finally, transient ORF-9b expression led to a strong induction of autophagy in cells. The induction of autophagy depended upon ATG5, a critical autophagy regulator, but the inhibition of MAVS signaling did not. These results indicate that SARS-CoV ORF-9b manipulates host cell mitochondria and mitochondrial function to help evade host innate immunity. This study has uncovered an important clue to the pathogenesis of SARS-CoV infection and illustrates the havoc that a small open reading frame can cause in cells.",,"['Shi, Chong-Shan', 'Qi, Hai-Yan', 'Boularan, Cedric', 'Huang, Ning-Na', 'Abu-Asab, Mones', 'Shelhamer, James H.', 'Kehrl, John H.']",,,,
,PMC,"Vaccines, new opportunities for a new society",http://dx.doi.org/10.1073/pnas.1402981111,PMC4151714,,,"Vaccination is the most effective medical intervention ever introduced and, together with clean water and sanitation, it has eliminated a large part of the infectious diseases that once killed millions of people. A recent study concluded that since 1924 in the United States alone, vaccines have prevented 40 million cases of diphtheria, 35 million cases of measles, and a total of 103 million cases of childhood diseases. A report from the World Health Organization states that today vaccines prevent 2.5 million deaths per year: Every minute five lives are saved by vaccines worldwide. Overall, vaccines have done and continue to do an excellent job in eliminating or reducing the impact of childhood diseases. Furthermore, thanks to new technologies, vaccines now have the potential to make an enormous contribution to the health of modern society by preventing and treating not only communicable diseases in all ages, but also noncommunicable diseases such as cancer and neurodegenerative disorders. The achievement of these results requires the development of novel technologies and health economic models able to capture not only the mere cost–benefit of vaccination, but also the value of health per se.",,"['Rappuoli, Rino', 'Pizza, Mariagrazia', 'Del Giudice, Giuseppe', 'De Gregorio, Ennio']",,,,
,PMC,Association of Interleukin-8 and Neutrophils with Nasal Symptom Severity During Acute Respiratory Infection,http://dx.doi.org/10.1002/jmv.24042,PMC4348013,,,"Using a large data set (n = 811), the relationship between acute respiratory infection illness severity and inflammatory biomarkers was investigated to determine whether certain symptoms are correlated more closely than others with the inflammatory biomarkers, interleukin-8 (IL-8) and nasal neutrophils. Participants with community acquired acute respiratory infection underwent nasal lavage for IL-8 and neutrophil testing, in addition to multiplex polymerase chain reaction (PCR) methods for the detection and identification of respiratory viruses. Information about symptoms was obtained throughout the duration of the illness episode using the well-validated Wisconsin Upper Respiratory Symptom Survey (WURSS-21). Global symptom severity was calculated by the area under the curve (AUC) plotting duration versus WURSS total. Of the specimens tested, 56% were positively identified for one or more of nine different respiratory viruses. During acute respiratory infection illness, both IL-8 and neutrophils positively correlate with AUC (r(s) = 0.082, P = 0.022; r(s) = 0.080, P = 0.030). IL-8 and neutrophils correlate with nasal symptom severity: runny nose (r = 0.13, P = <0.00001; r = 0.18, P = <0.003), plugged nose (r = 0.045, P = 0.003; r = 0.14, P = 0.058), and sneezing (r = −0.02, P = <0.0001; r = −0.0055, P = 0.31). Neutrophils correlate with some quality of life measures such as sleeping well (r = 0.15, P = 0.026). Thus, the study demonstrates that IL-8 and neutrophils are correlated with severity of nasal symptoms during acute respiratory infection. Further research is necessary to determine if the concentration of these or other biomarkers can predict the overall duration and severity of acute respiratory infection illness.",,"['Henriquez, Kelsey M.', 'Hayney, Mary S.', 'Xie, Yaoguo', 'Zhang, Zhengjun', 'Barrett, Bruce']",,,,
,PMC,Relationship of high CH50 level and interruption of cascade reaction of complement mRNA expression in acute venous thromboembolism patients,,PMC4161595,,,"In patients with pulmonary embolism (PE), forepart components of complements were activated. However there are interruption/decrease of cascade reaction and cytolytic effects in complement system. This study detected CRP, CH50, C3 and C4 levels in patients with venous thromboembolism (VTE) and compare with the imbalance of complement associated gene mRNA expression in PE patients. There was significant increase of CH50 in acute VTE patients. Even though CH50 increased significantly in acute VTE patients and had a relatively high sensitivity, cytolytic effects of complements might decrease, based on the genomics results of complement cascade reactions imbalance/interruption and increased total complements in VTE patients.",,"['Wen, Siwan', 'Yang, Fan', 'Wang, Lemin', 'Duan, Qianglin', 'Gong, Zhu', 'Lv, Wei']",,,,
,PMC,"Oxidized low-density lipoprotein, OXPAPC, corrects defects in maturation and cytokine secretion of peripheral blood dendritic cells from sepsis patients",,PMC4161548,,,"Objective: To investigate the expression differences in maturation and cytokine production of dendritic cells (DCs) from sepsis patients and the effect of oxidized phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OXPAPC) on DCs phenotypes. Methods: Peripheral blood mononuclear cells from 50 sepsis patients and 50 controls were cultured in the presence of GM-CSF, IL-4 and TNF-α to induce DCs maturation. DCs from sepsis patients were also treated with three different concentrations of OXPAPC. Cells were characterized with optical and electron microscopy, FACS analysis for CD1α, HLA-DR and CD86 on cell surface and ELISA analysis of IL-12p70 in the supernatant. Results: DCs from sepsis patients had smaller cell bodies and nucleus and had almost no surface projection. DCs had similar CD1α expression in sepsis patients (86.37 ± 17.24) and controls (88.58 ± 10.05). HLA-DR expression was dramatically reduced in sepsis patients (2.74 ± 5.15) compared to controls (198.35 ± 12.04). Similarly, CD86 expression was also drastically lower in sepsis patients (14.72 ± 4.83) than controls (154.56 ± 11.56). Furthermore, OXPAPC treatment of DCs from sepsis patients increased cell surface projection, HLA-DR and CD86 surface expression and IL-12p70 secretion in a dose-dependent manner. With 40 μg/ml of OXPAPC, DCs of sepsis patients have similar phenotypes observed in healthy controls. Conclusion: DCs from sepsis patients are defective in maturation and cytokine secretion and these defects can be corrected by OXPAPC treatment.",,"['Tan, Yun', 'Li, Jin-Xiu', 'Xiang, Xu-Dong', 'Lü, Jian-Lei']",,,,
,PMC,Intranasal sirna targeting c-kit reduces airway inflammation in experimental allergic asthma,,PMC4203163,,,"Allergic asthma is characterized by airway inflammation caused by infiltration and activation of inflammatory cells that produce cytokines. Many studies have revealed that c-kit, a proto-oncogene, and its ligand, stem cell factor (SCF), play an important role in the development of asthmatic inflammation. Intranasal small interference RNA (siRNA) nanoparticles targeting specific viral gene could inhibit airway inflammation. In this study, we assessed whether silencing of c-kit with intranasal small interference RNA could reduce inflammation in allergic asthma. A mouse model of experimental asthma was treated with intranasal administration of anti-c-kit siRNA to inhibit the expression of the c-kit gene. We assessed the inflammatory response in both anti-c-kit siRNA-treated and control mice. Local administration of siRNA effectively inhibited the expression of the c-kit gene and reduced airway mucus secretion and the infiltration of eosinophils in bronchoalveolar lavage fluid. Moreover, c-kit siRNA reduced the production of SCF, interleukin-4 (IL-4), and IL-5, but had no effect on interferon-γ (IFN-γ) generation. These results show that intranasal siRNA nanoparticles targeting c-kit can decrease the inflammatory response in experimental allergic asthma.",,"['Wu, Wei', 'Chen, Hui', 'Li, Ya-Ming', 'Wang, Sheng-Yu', 'Diao, Xin', 'Liu, Kai-Ge']",,,,
,PMC,Preparedness for molecular testing of Middle East respiratory syndrome coronavirus among laboratories in the Western Pacific Region,http://dx.doi.org/10.5365/WPSAR.2014.5.3.001,PMC4197189,,,,,"['Squires, Raynal C', 'Konings, Frank']",,,,
,PMC,Using Clinicians’ Search Query Data to Monitor Influenza Epidemics,http://dx.doi.org/10.1093/cid/ciu647,PMC4296132,,,"Search query information from a clinician's database, UpToDate, is shown to predict influenza epidemics in the United States in a timely manner. Our results show that digital disease surveillance tools based on experts' databases may be able to provide an alternative, reliable, and stable signal for accurate predictions of influenza outbreaks.",,"['Santillana, Mauricio', 'Nsoesie, Elaine O.', 'Mekaru, Sumiko R.', 'Scales, David', 'Brownstein, John S.']",,,,
,PMC,Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus,http://dx.doi.org/10.1073/pnas.1405889111,PMC4151778,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) currently spreads in humans and causes ∼36% fatality in infected patients. Believed to have originated from bats, MERS-CoV is genetically related to bat coronaviruses HKU4 and HKU5. To understand how bat coronaviruses transmit to humans, we investigated the receptor usage and cell entry activity of the virus-surface spike proteins of HKU4 and HKU5. We found that dipeptidyl peptidase 4 (DPP4), the receptor for MERS-CoV, is also the receptor for HKU4, but not HKU5. Despite sharing a common receptor, MERS-CoV and HKU4 spikes demonstrated functional differences. First, whereas MERS-CoV prefers human DPP4 over bat DPP4 as its receptor, HKU4 shows the opposite trend. Second, in the absence of exogenous proteases, both MERS-CoV and HKU4 spikes mediate pseudovirus entry into bat cells, whereas only MERS-CoV spike, but not HKU4 spike, mediates pseudovirus entry into human cells. Thus, MERS-CoV, but not HKU4, has adapted to use human DPP4 and human cellular proteases for efficient human cell entry, contributing to the enhanced pathogenesis of MERS-CoV in humans. These results establish DPP4 as a functional receptor for HKU4 and host cellular proteases as a host range determinant for HKU4. They also suggest that DPP4-recognizing bat coronaviruses threaten human health because of their spikes’ capability to adapt to human cells for cross-species transmissions.",,"['Yang, Yang', 'Du, Lanying', 'Liu, Chang', 'Wang, Lili', 'Ma, Cuiqing', 'Tang, Jian', 'Baric, Ralph S.', 'Jiang, Shibo', 'Li, Fang']",,,,
,PMC,Endosomal acidification and cathepsin L activity is required for calicivirus replication,http://dx.doi.org/10.1016/j.virol.2014.07.025,PMC4157107,,,"The role of cellular proteases and endosome maturation in the entry of caliciviruses including porcine enteric calicivirus (PEC), murine norovirus (MNV)-1 and feline calicivirus (FCV) were investigated. Treatment with chloroquine or cathepsin L inhibitors, but not cathepsin B inhibitors, significantly reduced the replication of PEC, MNV and FCV. When concentrated PEC, MNV or FCV were incubated with recombinant cathepsin L, the minor capsid protein VP2 of PEC or the major capsid protein VP1 of MNV and FCV were cleaved by the protease based on the Western blot analysis. Confocal microscopy analysis of PEC and MNV-1 showed that viral capsid proteins were retained in the endosomes in the presence of a cathepsin L inhibitor or chloroquine during virus entry. The results of this study suggest the important role of endosome maturation and cathepsin L in the entry of caliciviruses, and cathepsin L as a potential therapeutic target for calicivirus infection.",,"['Shivanna, Vinay', 'Kim, Yunjeong', 'Chang, Kyeong-Ok']",,,,
,PMC,Enhancement of blood-brain barrier permeability is required for intravenously administered virus neutralizing antibodies to clear an established rabies virus infection from the brain and prevent the development of rabies in mice,http://dx.doi.org/10.1016/j.antiviral.2014.07.013,PMC4171353,,,"Rabies virus (RABV) is a neurotropic virus that causes fatal disease in humans and animals. Currently there is no cure for rabies once clinical signs appear. It is believed that once RABV enters the central nervous system (CNS), virus neutralizing antibodies (VNAs) in the periphery cannot pass through the Blood–brain Barrier (BBB) and into the CNS. Furthermore, it has been hypothesized that VNAs produced in the CNS by invading B cells, rather than those produced in the periphery and then transported into the CNS, are important in clearing RABV from the CNS. In the present study, mouse serum containing VNA was administered intravenously into mice after infection with wild-type RABV. Our studies demonstrate that exogenous administration of VNAs is crucial in the clearance of RABV from the brain and prevent the development of rabies in both immunocompetent and immunocompromised mice as long as the BBB permeability remains enhanced. This present study therefore provides a foundation for the possibility of developing VNA therapy for clinical rabies in humans.",,"['Huang, Chien-Tsun', 'Li, Zhenguang', 'Huang, Ying', 'Zhang, Guoqing', 'Zhou, Ming', 'Chai, Qingqing', 'Wu, Hua', 'Fu, Zhen F.']",,,,
,PMC,An immune competent mouse model for the characterization of recombinant measles vaccines,http://dx.doi.org/10.4161/hv.34358,PMC4514240,,,"Today, immune compromised interferon-α-receptor deficient mice expressing hCD46 (IFNARCD46tg) are usually used for measles virus (MV) based vaccine characterization. However, for the development of MV-based recombinant vaccine candidates (rMV), an immune competent mouse model is desirable in order to induce and evaluate meaningful immune response. In this study, humoral and cellular immune response induced by rMV in immune competent mice expressing human MV receptor CD46 (hCD46tg) were compared with those induced in wild-type black/6, and IFNARCD46tg mice. All three strains developed humoral and cellular response against MV, whereas only hCD46tg and IFNARCD46tg mice developed a humoral response against the transgene. Differences were observed in the magnitude of the response, where the IFNARCD46tg mice displayed the strongest immune responses, followed by the hCD46tg mice and the black/6 mice. Interestingly, hCD46tg and wt black/6 mice showed a predominant CD4(+) T-cell response against MV-N, whereas IFNARCD46tg mice developed both, CD4(+) and CD8(+) T-cell response against MV-N. Analysis of the cytokine profile of MV-N specific CD4(+) T-cells and transgene (SIVgag) specific CD8(+) T-cells revealed qualitative differences of the T-cell responses; noticeably a significant reduction of the frequency of CD4(+)IL-2(+) expressing cells in IFNARCD46tg mice as compared with hCD46tg or wt black/6 mice. We show in this study significant quantitative and qualitative differences in immune responses between immune competent and immune-compromised mice. Our results therefore highlight the importance of the animal model and support the use of hCD46tg mice as mouse model for the characterization of the immunological profile induced by recombinant measles virus vaccine candidates.",,"['Marty, René R', 'Knuchel, Marlyse C', 'Morin, Teldja Neige Azzouz', 'Naim, Hussein Y']",,,,
,PMC,Clinical and Laboratory Findings of the First Imported Case of Middle East Respiratory Syndrome Coronavirus to the United States,http://dx.doi.org/10.1093/cid/ciu635,PMC4650772,,,"Background. The Middle East respiratory syndrome coronavirus (MERS-CoV) was discovered September 2012 in the Kingdom of Saudi Arabia (KSA). The first US case of MERS-CoV was confirmed on 2 May 2014. Methods. We summarize the clinical symptoms and signs, laboratory and radiologic findings, and MERS-CoV–specific tests. Results. The patient is a 65-year-old physician who worked in a hospital in KSA where MERS-CoV patients were treated. His illness onset included malaise, myalgias, and low-grade fever. He flew to the United States on day of illness (DOI) 7. His first respiratory symptom, a dry cough, developed on DOI 10. On DOI 11, he presented to an Indiana hospital as dyspneic, hypoxic, and with a right lower lobe infiltrate on chest radiography. On DOI 12, his serum tested positive by real-time reverse transcription polymerase chain reaction (rRT-PCR) for MERS-CoV and showed high MERS-CoV antibody titers, whereas his nasopharyngeal swab was rRT-PCR negative. Expectorated sputum was rRT-PCR positive the following day, with a high viral load (5.31 × 10(6) copies/mL). He was treated with antibiotics, intravenous immunoglobulin, and oxygen by nasal cannula. He was discharged on DOI 22. The genome sequence was similar (>99%) to other known MERS-CoV sequences, clustering with those from KSA from June to July 2013. Conclusions. This patient had a prolonged nonspecific prodromal illness before developing respiratory symptoms. Both sera and sputum were rRT-PCR positive when nasopharyngeal specimens were negative. US clinicians must be vigilant for MERS-CoV in patients with febrile and/or respiratory illness with recent travel to the Arabian Peninsula, especially among healthcare workers.",,"['Kapoor, Minal', 'Pringle, Kimberly', 'Kumar, Alan', 'Dearth, Stephanie', 'Liu, Lixia', 'Lovchik, Judith', 'Perez, Omar', 'Pontones, Pam', 'Richards, Shawn', 'Yeadon-Fagbohun, Jaime', 'Breakwell, Lucy', 'Chea, Nora', 'Cohen, Nicole J.', 'Schneider, Eileen', 'Erdman, Dean', 'Haynes, Lia', 'Pallansch, Mark', 'Tao, Ying', 'Tong, Suxiang', 'Gerber, Susan', 'Swerdlow, David', 'Feikin, Daniel R.']",,,,
,PMC,"Measles virus: A pathogen, vaccine, and a vector",http://dx.doi.org/10.4161/hv.34298,PMC4514292,,,"Measles was an inevitable infection during the human development with substantial degree of morbidity and mortality. The severity of measles virus (MV) infection was largely contained by the development of a live attenuated vaccine that was introduced into the vaccination programs. However, all efforts to eradicate the disease failed and continued to annually result in significant deaths. The development of molecular biology techniques allowed the rescue of MV from cDNA that enabled important insights into a variety of aspects of the biology of the virus and its pathogenesis. Subsequently these technologies facilitated the development of novel vaccine candidates that induce immunity against measles and other pathogens. Based on the promising prospective, the use of MV as a recombinant vaccine and a therapeutic vector is addressed.",,"Naim, Hussein Y",,,,
,PMC,CORONAVIRUS VIRULENCE GENES WITH MAIN FOCUS ON SARS-CoV ENVELOPE GENE,http://dx.doi.org/10.1016/j.virusres.2014.07.024,PMC4261026,,,"Coronavirus (CoV) infection is usually detected by cellular sensors, which trigger the activation of the innate immune system. Nevertheless, CoVs have evolved viral proteins that target different signaling pathways to counteract innate immune responses. Some CoV proteins act as antagonists of interferon (IFN) by inhibiting IFN production or signaling, aspects that are briefly addressed in this review. After CoV infection, potent cytokines relevant in controlling virus infections and priming adaptive immune responses are also generated. However, an uncontrolled induction of these proinflammatory cytokines can lead to pathogenesis and disease severity as described for SARS-CoV and MERS-CoV. The cellular pathways mediated by interferon regulatory factor (IRF)-3 and 7, activating transcription factor (ATF)-2/jun, activator protein (AP)-1, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and nuclear factor of activated T cells (NF-AT), are the main drivers of the inflammatory response triggered after viral infections, with NF-κB pathway the most frequently activated. Key CoV proteins involved in the regulation of these pathways and the proinflammatory immune response are revisited in this manuscript. It has been shown that the envelope (E) protein plays a variable role in CoV morphogenesis, depending on the CoV genus, being absolutely essential in some cases (genus α CoVs such as TGEV, and genus β CoVs such as MERS-CoV), but not in others (genus β CoVs such as MHV or SARS-CoV). A comprehensive accumulation of data has shown that the relatively small E protein elicits a strong influence on the interaction of SARS-CoV with the host. In fact, after infection with viruses in which this protein has been deleted, increased cellular stress and unfolded protein responses, apoptosis, and augmented host immune responses were observed. In contrast, the presence of E protein activated a pathogenic inflammatory response that may cause death in animal models and in humans. The modification or deletion of different motifs within E protein, including the transmembrane domain that harbors an ion channel activity, small sequences within the middle region of the carboxy-terminus of E protein, and its most carboxy-terminal end, which contains a PDZ domain-binding motif (PBM) is sufficient to attenuate the virus. Interestingly, a comprehensive collection of SARS-CoVs in which these motifs have been modified elicited full and long-term protection even in old mice, making those deletion mutants promising vaccine candidates. These data indicate that despite its small size, E protein drastically influences the replication of CoVs and their pathogenicity. Although E protein is not essential for CoV genome replication or subgenomic mRNA synthesis, it affects virus morphogenesis, budding, assembly, intracellular trafficking, and virulence. In fact, E protein is responsible in a significant proportion of the inflammasome activation and the associated inflammation elicited by SARS-CoV in the lung parenchyma. This exacerbated inflammation causes edema accumulation leading to acute respiratory distress syndrome (ARDS) and, frequently, to the death of infected animal models or human patients.",,"['DeDiego, Marta L.', 'Nieto-Torres, Jose L.', 'Jimenez-Guardeño, Jose M.', 'Regla-Nava, Jose A.', 'Castaño-Rodriguez, Carlos', 'Fernandez-Delgado, Raul', 'Usera, Fernando', 'Enjuanes, Luis']",,,,
,PMC,Severity of Rhinovirus Infection in Hospitalized Adults Is Unrelated to Genotype,http://dx.doi.org/10.1309/AJCPHIKRJC67AAZJ,PMC4332627,,,"OBJECTIVES: To determine whether rhinovirus (RV) species is associated with more severe clinical illness in adults. METHODS: Seventy-two RV-positive viral respiratory samples from adult patients were sequenced and analyzed phylogenetically after reverse transcriptase polymerase chain reaction of the region spanning the VP4 gene and 5′ terminus of the VP2 gene. The clinical features and severity of illness associated with the different RV species were compared. RESULTS: Phylogenetic analysis identified three distinct clusters as RV-A (54%), B (11%), or C (35%) species. In an unadjusted model, patients with RV-B infection were significantly more likely to have the composite outcome variable of death or intensive care unit admission (P = .03), but this effect diminished when controlling for patient sex. A logistic model of the relationship between RV species and adverse outcomes produced nonsignificant odds ratios when controlling for patient sex. CONCLUSIONS: Infection with RV-A or RV-B was associated with greater severity of illness in our adult population; however, the association disappeared after controlling for confounders.",,"['McCulloch, Denise J.', 'Sears, Marti H.', 'Jacob, Jesse T.', 'Lyon, G. Marshall', 'Burd, Eileen M.', 'Caliendo, Angela M.', 'Hill, Charles E.', 'Nix, W. Allan', 'Oberste, M. Steven', 'Kraft, Colleen S.']",,,,
,PMC,Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture,http://dx.doi.org/10.1128/AAC.03011-14,PMC4136071,,,"Coronaviruses can cause respiratory and enteric disease in a wide variety of human and animal hosts. The 2003 outbreak of severe acute respiratory syndrome (SARS) first demonstrated the potentially lethal consequences of zoonotic coronavirus infections in humans. In 2012, a similar previously unknown coronavirus emerged, Middle East respiratory syndrome coronavirus (MERS-CoV), thus far causing over 650 laboratory-confirmed infections, with an unexplained steep rise in the number of cases being recorded over recent months. The human MERS fatality rate of ∼30% is alarmingly high, even though many deaths were associated with underlying medical conditions. Registered therapeutics for the treatment of coronavirus infections are not available. Moreover, the pace of drug development and registration for human use is generally incompatible with strategies to combat emerging infectious diseases. Therefore, we have screened a library of 348 FDA-approved drugs for anti-MERS-CoV activity in cell culture. If such compounds proved sufficiently potent, their efficacy might be directly assessed in MERS patients. We identified four compounds (chloroquine, chlorpromazine, loperamide, and lopinavir) inhibiting MERS-CoV replication in the low-micromolar range (50% effective concentrations [EC(50)s], 3 to 8 μM). Moreover, these compounds also inhibit the replication of SARS coronavirus and human coronavirus 229E. Although their protective activity (alone or in combination) remains to be assessed in animal models, our findings may offer a starting point for treatment of patients infected with zoonotic coronaviruses like MERS-CoV. Although they may not necessarily reduce viral replication to very low levels, a moderate viral load reduction may create a window during which to mount a protective immune response.",,"['de Wilde, Adriaan H.', 'Jochmans, Dirk', 'Posthuma, Clara C.', 'Zevenhoven-Dobbe, Jessika C.', 'van Nieuwkoop, Stefan', 'Bestebroer, Theo M.', 'van den Hoogen, Bernadette G.', 'Neyts, Johan', 'Snijder, Eric J.']",,,,
,PMC,"Evaluation of SSYA10-001 as a Replication Inhibitor of Severe Acute Respiratory Syndrome, Mouse Hepatitis, and Middle East Respiratory Syndrome Coronaviruses",http://dx.doi.org/10.1128/AAC.02994-14,PMC4136041,,,"We have previously shown that SSYA10-001 blocks severe acute respiratory syndrome coronavirus (SARS-CoV) replication by inhibiting SARS-CoV helicase (nsp13). Here, we show that SSYA10-001 also inhibits replication of two other coronaviruses, mouse hepatitis virus (MHV) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). A putative binding pocket for SSYA10-001 was identified and shown to be similar in SARS-CoV, MERS-CoV, and MHV helicases. These studies show that it is possible to target multiple coronaviruses through broad-spectrum inhibitors.",,"['Adedeji, Adeyemi O.', 'Singh, Kamalendra', 'Kassim, Ademola', 'Coleman, Christopher M.', 'Elliott, Ruth', 'Weiss, Susan R.', 'Frieman, Matthew B.', 'Sarafianos, Stefan G.']",,,,
,PMC,Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/AAC.03036-14,PMC4136000,,,"Outbreaks of emerging infections present health professionals with the unique challenge of trying to select appropriate pharmacologic treatments in the clinic with little time available for drug testing and development. Typically, clinicians are left with general supportive care and often untested convalescent-phase plasma as available treatment options. Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to clinicians, researchers, public health agencies, drug developers, and funding agencies. Given the development times and manufacturing requirements for new products, repurposing of existing drugs is likely the only solution for outbreaks due to emerging viruses. In the studies described here, a library of 290 compounds was screened for antiviral activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Selection of compounds for inclusion in the library was dependent on current or previous FDA approval or advanced clinical development. Some drugs that had a well-defined cellular pathway as target were included. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to 13 different classes of pharmaceuticals, including inhibitors of estrogen receptors used for cancer treatment and inhibitors of dopamine receptor used as antipsychotics. The drugs identified in these screens provide new targets for in vivo studies as well as incorporation into ongoing clinical studies.",,"['Dyall, Julie', 'Coleman, Christopher M.', 'Hart, Brit J.', 'Venkataraman, Thiagarajan', 'Holbrook, Michael R.', 'Kindrachuk, Jason', 'Johnson, Reed F.', 'Olinger, Gene G.', 'Jahrling, Peter B.', 'Laidlaw, Monique', 'Johansen, Lisa M.', 'Lear-Rooney, Calli M.', 'Glass, Pamela J.', 'Hensley, Lisa E.', 'Frieman, Matthew B.']",,,,
,PMC,Alternative Screening Approaches for Discovery of Middle East Respiratory Syndrome Coronavirus Inhibitors,http://dx.doi.org/10.1128/AAC.03406-14,PMC4135998,,,Two coronaviruses causing severe respiratory disease and high mortality rates emerging within the past dozen years reinforces the need for clinically efficacious antivirals targeting coronaviruses. Alternative screening approaches for antivirals against the recently emergent Middle East respiratory syndrome coronavirus (MERS-CoV) may provide lead compounds to address this need. Two Antimicrobial Agents and Chemotherapy (AAC) papers screened libraries of approved compounds that may potentially be repurposed as MERS-CoV antivirals. A third AAC paper showed that a previously described severe acute respiratory syndrome coronavirus (SARS-CoV) helicase inhibitor also has activity against MERS-CoV.,,"LaFemina, Robert L.",,,,
,PMC,Mechanisms of Antiviral Action of Plant Antimicrobials against Murine Norovirus,http://dx.doi.org/10.1128/AEM.00402-14,PMC4135763,,,"Numerous plant compounds have antibacterial or antiviral properties; however, limited research has been conducted with nonenveloped viruses. The efficacies of allspice oil, lemongrass oil, and citral were evaluated against the nonenveloped murine norovirus (MNV), a human norovirus surrogate. The antiviral mechanisms of action were also examined using an RNase I protection assay, a host cell binding assay, and transmission electron microscopy. All three antimicrobials produced significant reductions (P ≤ 0.05) in viral infectivity within 6 h of exposure (0.90 log(10) to 1.88 log(10)). After 24 h, the reductions were 2.74, 3.00, and 3.41 log(10) for lemongrass oil, citral, and allspice oil, respectively. The antiviral effect of allspice oil was both time and concentration dependent; the effects of lemongrass oil and citral were time dependent. Based on the RNase I assay, allspice oil appeared to act directly upon the viral capsid and RNA. The capsids enlarged from ≤35 nm to up to 75 nm following treatment. MNV adsorption to host cells was not significantly affected. Alternatively, the capsid remained intact following exposure to lemongrass oil and citral, which appeared to coat the capsid, causing nonspecific and nonproductive binding to host cells that did not lead to successful infection. Such contrasting effects between allspice oil and both lemongrass oil and citral suggest that though different plant compounds may yield similar reductions in virus infectivity, the mechanisms of inactivation may be highly varied and specific to the antimicrobial. This study demonstrates the antiviral properties of allspice oil, lemongrass oil, and citral against MNV and thus indicates their potential as natural food and surface sanitizers to control noroviruses.",,"['Gilling, Damian H.', 'Kitajima, Masaaki', 'Torrey, Jason R.', 'Bright, Kelly R.']",,,,
,PMC,Adaptation and Attenuation of Duck Tembusu Virus Strain Du/CH/LSD/110128 following Serial Passage in Chicken Embryos,http://dx.doi.org/10.1128/CVI.00154-14,PMC4135909,,,"Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has caused massive economic losses to the duck industry in China. In the current study, a virulent strain of DTMUV, designated Du/CH/LSD/110128, was isolated from the livers of diseased ducks and attenuated by serial passage in embryonated chicken eggs. The virus was partially attenuated after 50 and 70 passages and was fully attenuated after 90 passages, based on mortality and morbidity rates and viral loads in inoculated ducklings. Fourteen amino acid substitutions were observed in the capsid, prM, envelope, NS1, NS3, NS4A, NS4B, and NS5 proteins of the fully attenuated strain of Du/CH/LSD/110128, which might be responsible for the observed changes in replication and pathogenicity. A 72-nucleotide deletion was also observed in the 3′ untranslated region of the virus after 30 passages. The fully attenuated virus retained the immunogenicity of the parental strain, providing effective protection to challenge with virulent Du/CH/LSD/110128, and may represent a suitable candidate as a vaccine strain against DTMUV infection in ducks. Our results also lay the foundation for future studies on the replication and pathogenic mechanisms of DTMUV.",,"['Sun, Ling', 'Li, Yunxia', 'Zhang, Yue', 'Han, Zongxi', 'Xu, Yang', 'Kong, Xiangang', 'Liu, Shengwang']",,,,
,PMC,Endocytosis of Viruses and Bacteria,http://dx.doi.org/10.1101/cshperspect.a016972,PMC4107984,,,"Of the many pathogens that infect humans and animals, a large number use cells of the host organism as protected sites for replication. To reach the relevant intracellular compartments, they take advantage of the endocytosis machinery and exploit the network of endocytic organelles for penetration into the cytosol or as sites of replication. In this review, we discuss the endocytic entry processes used by viruses and bacteria and compare the strategies used by these dissimilar classes of pathogens.",,"['Cossart, Pascale', 'Helenius, Ari']",,,,
,PMC,T-cell-mediated immune response to respiratory coronaviruses,http://dx.doi.org/10.1007/s12026-014-8534-z,PMC4125530,,,"Emerging respiratory coronaviruses such as the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV) pose potential biological threats to humans. SARS and MERS are manifested as severe atypical pneumonia associated with high morbidity and mortality in humans. The majority of studies carried out in SARS-CoV-infected humans and animals attribute a dysregulated/exuberant innate response as a leading contributor to SARS-CoV-mediated pathology. A decade after the 2002–2003 SARS epidemic, we do not have any approved preventive or therapeutic agents available in case of re-emergence of SARS-CoV or other related viruses. A strong neutralizing antibody response generated against the spike (S) glycoprotein of SARS-CoV is completely protective in the susceptible host. However, neutralizing antibody titers and the memory B cell response are short-lived in SARS-recovered patients and the antibody will target primary homologous strain. Interestingly, the acute phase of SARS in humans is associated with a severe reduction in the number of T cells in the blood. Surprisingly, only a limited number of studies have explored the role of the T cell-mediated adaptive immune response in respiratory coronavirus pathogenesis. In this review, we discuss the role of anti-virus CD4 and CD8 T cells during respiratory coronavirus infections with a special emphasis on emerging coronaviruses.",,"['Channappanavar, Rudragouda', 'Zhao, Jincun', 'Perlman, Stanley']",,,,
,PMC,Misfolded Proteins Induce Aggregation of the Lectin Yos9,http://dx.doi.org/10.1074/jbc.M114.583344,PMC4162170,,,"A substantial fraction of nascent proteins delivered into the endoplasmic reticulum (ER) never reach their native conformations. Eukaryotes use a series of complementary pathways to efficiently recognize and dispose of these terminally misfolded proteins. In this process, collectively termed ER-associated degradation (ERAD), misfolded proteins are retrotranslocated to the cytosol, polyubiquitinated, and degraded by the proteasome. Although there has been great progress in identifying ERAD components, how these factors accurately identify substrates remains poorly understood. The targeting of misfolded glycoproteins in the ER lumen for ERAD requires the lectin Yos9, which recognizes the glycan species found on terminally misfolded proteins. In a role that remains poorly characterized, Yos9 also binds the protein component of ERAD substrates. Here, we identified a 45-kDa domain of Yos9, consisting of residues 22–421, that is proteolytically stable, highly structured, and able to fully support ERAD in vivo. In vitro binding studies show that Yos9(22–421) exhibits sequence-specific recognition of linear peptides from the ERAD substrate, carboxypeptidase Y G255R (CPY*), and binds a model unfolded peptide ΔEspP and protein Δ131Δ in solution. Binding of Yos9 to these substrates results in their cooperative aggregation. Although the physiological consequences of this substrate-induced aggregation remain to be seen, it has the potential to play a role in the regulation of ERAD.",,"['Smith, Melanie H.', 'Rodriguez, Edwin H.', 'Weissman, Jonathan S.']",,,,
,PMC,Hypertrophic Adenoid Is a Major Infection Site of Human Bocavirus 1,http://dx.doi.org/10.1128/JCM.00870-14,PMC4136160,,,"Human bocavirus 1 (HBoV1) is associated with respiratory infections worldwide, mainly in children. Similar to other parvoviruses, it is believed that HBoV1 can persist for long periods of time in humans, probably through maintaining concatemers of the virus single-stranded DNA genome in the nuclei of infected cells. Recently, HBoV-1 was detected in high rates in adenoid and palatine tonsils samples from patients with chronic adenotonsillar diseases, but nothing is known about the virus replication levels in those tissues. A 3-year prospective hospital-based study was conducted to detect and quantify HBoV1 DNA and mRNAs in samples of the adenoids (AD), palatine tonsils (PT), nasopharyngeal secretions (NPS), and peripheral blood (PB) from patients undergoing tonsillectomy for tonsillar hypertrophy or recurrent tonsillitis. HBoV1 was detected in 25.3% of the AD samples, while the rates of detection in the PT, NPS, and PB samples were 7.2%, 10.5%, and 1.7%, respectively. The viral loads were higher in AD samples, and 27.3% of the patients with HBoV had mRNA detectable in this tissue. High viral loads and detectable mRNA in the AD were associated with HBoV1 detection in the other sample sites. The adenoids are an important site of HBoV1 replication and persistence in children with tonsillar hypertrophy. The adenoids contain high HBoV1 loads and are frequently positive for HBoV mRNA, and this is associated with the detection of HBoV1 in secretions.",,"['Proenca-Modena, J. L.', 'Paula, F. E.', 'Buzatto, G. P.', 'Carenzi, L. R.', 'Saturno, T. H.', 'Prates, M. C.', 'Silva, M. L.', 'Delcaro, L. S.', 'Valera, F. C. P.', 'Tamashiro, E.', 'Anselmo-Lima, W. T.', 'Arruda, E.']",,,,
,PMC,"Kimchi Methanol Extract and the Kimchi Active Compound, 3′-(4′-Hydroxyl-3′,5′-Dimethoxyphenyl)Propionic Acid, Downregulate CD36 in THP-1 Macrophages Stimulated by oxLDL",http://dx.doi.org/10.1089/jmf.2013.2943,PMC4126270,,,"Macrophage foam cell formation by oxidized low-density lipoprotein (oxLDL) is a key step in the progression of atherosclerosis, which is involved in cholesterol influx and efflux in macrophages mediated by related proteins such as peroxisome proliferator-activated receptor γ (PPARγ), CD36, PPARα, liver-X receptor α (LXRα), and ATP-binding cassette transporter A1 (ABCA1). The aim of this study was to investigate the beneficial effects of kimchi methanol extract (KME) and a kimchi active compound, 3-(4′-hydroxyl-3′,5′-dimethoxyphenyl)propionic acid (HDMPPA) on cholesterol flux in THP-1-derived macrophages treated with oxLDL. The effects of KME and HDMPPA on cell viability and lipid peroxidation were determined. Furthermore, the protein expression of PPARγ, CD36, PPARα, LXRα, and ABCA1 was examined. OxLDL strongly induced cell death and lipid peroxidation in THP-1-derived macrophages. However, KME and HDMPPA significantly improved cell viability and inhibited lipid peroxidation induced by oxLDL in THP-1-derived macrophages (P<.05). Moreover, KME and HDMPPA suppressed CD36 and PPARγ expressions, both of which participate in cholesterol influx. In contrast, KME and HDMPPA augmented LXRα, PPARα, and ABCA1 expression, which are associated with cholesterol efflux. Consequently, KME and HDMPPA suppressed lipid accumulation. These results indicate that KME and HDMPPA may inhibit lipid accumulation, in part, by regulating cholesterol influx- and efflux-related proteins. These findings will thus be useful for future prevention strategies against atherosclerosis.",,"['Yun, Ye-Rang', 'Kim, Hyun-Ju', 'Song, Yeong-Ok']",,,,
,PMC,Deep Sequencing of HIV-Infected Cells: Insights into Nascent Transcription and Host-Directed Therapy,http://dx.doi.org/10.1128/JVI.00768-14,PMC4136300,,,"Polyadenylated mature mRNAs are the focus of standard transcriptome analyses. However, the profiling of nascent transcripts, which often include nonpolyadenylated RNAs, can unveil novel insights into transcriptional regulation. Here, we separately sequenced total RNAs (Total RNAseq) and mRNAs (mRNAseq) from the same HIV-1-infected human CD4(+) T cells. We found that many nonpolyadenylated RNAs were differentially expressed upon HIV-1 infection, and we identified 8 times more differentially expressed genes at 12 h postinfection by Total RNAseq than by mRNAseq. These expression changes were also evident by concurrent changes in introns and were recapitulated by later mRNA changes, revealing an unexpectedly significant delay between transcriptional initiation and mature mRNA production early after HIV-1 infection. We computationally derived and validated the underlying regulatory programs, and we predicted drugs capable of reversing these HIV-1-induced expression changes followed by experimental confirmation. Our results show that combined total and mRNA transcriptome analysis is essential for fully capturing the early host response to virus infection and provide a framework for identifying candidate drugs for host-directed therapy against HIV/AIDS. IMPORTANCE In this study, we used mass sequencing to identify genes differentially expressed in CD4(+) T cells during HIV-1 infection. To our surprise, we found many differentially expressed genes early after infection by analyzing both newly transcribed unprocessed pre-mRNAs and fully processed mRNAs, but not by analyzing mRNAs alone, indicating a significant delay between transcription initiation and mRNA production early after HIV-1 infection. These results also show that important findings could be missed by the standard practice of analyzing mRNAs alone. We then derived the regulatory mechanisms driving the observed expression changes using integrative computational analyses. Further, we predicted drugs that could reverse the observed expression changes induced by HIV-1 infection and showed that one of the predicted drugs indeed potently inhibited HIV-1 infection. This shows that it is possible to identify candidate drugs for host-directed therapy against HIV/AIDS using our genomics-based approach.",,"['Peng, Xinxia', 'Sova, Pavel', 'Green, Richard R.', 'Thomas, Matthew J.', 'Korth, Marcus J.', 'Proll, Sean', 'Xu, Jiabao', 'Cheng, Yanbing', 'Yi, Kang', 'Chen, Li', 'Peng, Zhiyu', 'Wang, Jun', 'Palermo, Robert E.', 'Katze, Michael G.']",,,,
,PMC,Dependence of Coronavirus RNA Replication on an NH(2)-Terminal Partial Nonstructural Protein 1 in cis,http://dx.doi.org/10.1128/JVI.00738-14,PMC4136265,,,"Genomes of positive (+)-strand RNA viruses use cis-acting signals to direct both translation and replication. Here we examine two 5′-proximal cis-replication signals of different character in a defective interfering (DI) RNA of the bovine coronavirus (BCoV) that map within a 322-nucleotide (nt) sequence (136 nt from the genomic 5′ untranslated region and 186 nt from the nonstructural protein 1 [nsp1]-coding region) not found in the otherwise-identical nonreplicating subgenomic mRNA7 (sgmRNA7). The natural DI RNA is structurally a fusion of the two ends of the BCoV genome that results in a single open reading frame between a partial nsp1-coding region and the entire N gene. (i) In the first examination, mutation analyses of a recently discovered long-range RNA-RNA base-paired structure between the 5′ untranslated region and the partial nsp1-coding region showed that it, possibly in concert with adjacent stem-loops, is a cis-acting replication signal in the (+) strand. We postulate that the higher-order structure promotes (+)-strand synthesis. (ii) In the second examination, analyses of multiple frame shifts, truncations, and point mutations within the partial nsp1-coding region showed that synthesis of a PEFP core amino acid sequence within a group A lineage betacoronavirus-conserved NH(2)-proximal WAPEFPWM domain is required in cis for DI RNA replication. We postulate that the nascent protein, as part of an RNA-associated translating complex, acts to direct the DI RNA to a critical site, enabling RNA replication. We suggest that these results have implications for viral genome replication and explain, in part, why coronavirus sgmRNAs fail to replicate. IMPORTANCE cis-Acting RNA and protein structures that regulate (+)-strand RNA virus genome synthesis are potential sites for blocking virus replication. Here we describe two: a previously suspected 5′-proximal long-range higher-order RNA structure and a novel nascent NH(2)-terminal protein component of nsp1 that are common among betacoronaviruses of group A lineage.",,"['Su, Yu-Pin', 'Fan, Yi-Hsin', 'Brian, David A.']",,,,
,PMC,Disease Severity Is Associated with Differential Gene Expression at the Early and Late Phases of Infection in Nonhuman Primates Infected with Different H5N1 Highly Pathogenic Avian Influenza Viruses,http://dx.doi.org/10.1128/JVI.00907-14,PMC4136255,,,"Occasional transmission of highly pathogenic avian H5N1 influenza viruses to humans causes severe pneumonia with high mortality. To better understand the mechanisms via which H5N1 viruses induce severe disease in humans, we infected cynomolgus macaques with six different H5N1 strains isolated from human patients and compared their pathogenicity and the global host responses to the virus infection. Although all H5N1 viruses replicated in the respiratory tract, there was substantial heterogeneity in their replicative ability and in the disease severity induced, which ranged from asymptomatic to fatal. A comparison of global gene expression between severe and mild disease cases indicated that interferon-induced upregulation of genes related to innate immunity, apoptosis, and antigen processing/presentation in the early phase of infection was limited in severe disease cases, although interferon expression was upregulated in both severe and mild cases. Furthermore, coexpression analysis of microarray data, which reveals the dynamics of host responses during the infection, demonstrated that the limited expression of these genes early in infection led to a failure to suppress virus replication and to the hyperinduction of genes related to immunity, inflammation, coagulation, and homeostasis in the late phase of infection, resulting in a more severe disease. Our data suggest that the attenuated interferon-induced activation of innate immunity, apoptosis, and antigen presentation in the early phase of H5N1 virus infection leads to subsequent severe disease outcome. IMPORTANCE Highly pathogenic avian H5N1 influenza viruses sometimes transmit to humans and cause severe pneumonia with ca. 60% lethality. The continued circulation of these viruses poses a pandemic threat; however, their pathogenesis in mammals is not fully understood. We, therefore, investigated the pathogenicity of six H5N1 viruses and compared the host responses of cynomolgus macaques to the virus infection. We identified differences in the viral replicative ability of and in disease severity caused by these H5N1 viruses. A comparison of global host responses between severe and mild disease cases identified the limited upregulation of interferon-stimulated genes early in infection in severe cases. The dynamics of the host responses indicated that the limited response early in infection failed to suppress virus replication and led to hyperinduction of pathological condition-related genes late in infection. These findings provide insight into the pathogenesis of H5N1 viruses in mammals.",,"['Muramoto, Yukiko', 'Shoemaker, Jason E.', 'Le, Mai Quynh', 'Itoh, Yasushi', 'Tamura, Daisuke', 'Sakai-Tagawa, Yuko', 'Imai, Hirotaka', 'Uraki, Ryuta', 'Takano, Ryo', 'Kawakami, Eiryo', 'Ito, Mutsumi', 'Okamoto, Kiyoko', 'Ishigaki, Hirohito', 'Mimuro, Hitomi', 'Sasakawa, Chihiro', 'Matsuoka, Yukiko', 'Noda, Takeshi', 'Fukuyama, Satoshi', 'Ogasawara, Kazumasa', 'Kitano, Hiroaki', 'Kawaoka, Yoshihiro']",,,,
,PMC,"Host Species Restriction of Middle East Respiratory Syndrome Coronavirus through Its Receptor, Dipeptidyl Peptidase 4",http://dx.doi.org/10.1128/JVI.00676-14,PMC4136254,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and ferret cells enabled MERS-CoV replication, whereas expression of hamster or ferret DPP4 did not. Modeling the binding energies of MERS-CoV spike protein RBD to DPP4 of human (susceptible) or hamster (nonsusceptible) identified five amino acid residues involved in the DPP4-RBD interaction. Expression of hamster DPP4 containing the five human DPP4 amino acids rendered BHK cells susceptible to MERS-CoV, whereas expression of human DPP4 containing the five hamster DPP4 amino acids did not. Using the same approach, the potential of MERS-CoV to utilize the DPP4s of common Middle Eastern livestock was investigated. Modeling of the DPP4 and MERS-CoV RBD interaction predicted the ability of MERS-CoV to bind the DPP4s of camel, goat, cow, and sheep. Expression of the DPP4s of these species on BHK cells supported MERS-CoV replication. This suggests, together with the abundant DPP4 presence in the respiratory tract, that these species might be able to function as a MERS-CoV intermediate reservoir. IMPORTANCE The ongoing outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 701 laboratory-confirmed cases to date, with 249 fatalities. Although bats and dromedary camels have been identified as potential MERS-CoV hosts, the virus has so far not been isolated from any species other than humans. The inability of MERS-CoV to infect commonly used animal models, such as hamster, mice, and ferrets, indicates the presence of a species barrier. We show that the MERS-CoV receptor DPP4 plays a pivotal role in the observed species tropism of MERS-CoV and subsequently identified the amino acids in DPP4 responsible for this restriction. Using a combined modeling and experimental approach, we predict that, based on the ability of MERS-CoV to utilize the DPP4 of common Middle East livestock species, such as camels, goats, sheep, and cows, these form a potential MERS-CoV intermediate host reservoir species.",,"['van Doremalen, Neeltje', 'Miazgowicz, Kerri L.', 'Milne-Price, Shauna', 'Bushmaker, Trenton', 'Robertson, Shelly', 'Scott, Dana', 'Kinne, Joerg', 'McLellan, Jason S.', 'Zhu, Jiang', 'Munster, Vincent J.']",,,,
,PMC,Porcine Epidemic Diarrhea Virus Nucleocapsid Protein Antagonizes Beta Interferon Production by Sequestering the Interaction between IRF3 and TBK1,http://dx.doi.org/10.1128/JVI.00700-14,PMC4136253,,,"Porcine epidemic diarrhea virus (PEDV), a porcine enteropathogenic coronavirus, causes lethal watery diarrhea in piglets and results in large economic losses in many Asian and European countries. A large-scale outbreak of porcine epidemic diarrhea occurred in China in 2010, and the virus emerged in the United States in 2013 and spread rapidly, posing significant economic and public health concerns. Previous studies have shown that PEDV infection inhibits the synthesis of type I interferon (IFN), and viral papain-like protease 2 has been identified as an IFN antagonist. In this study, we found that the PEDV-encoded nucleocapsid (N) protein also inhibits Sendai virus-induced IFN-β production, IFN-stimulated gene expression, and activation of the transcription factors IFN regulatory factor 3 (IRF3) and NF-κB. We also found that N protein significantly impedes the activation of the IFN-β promoter stimulated by TBK1 or its upstream molecules (RIG-I, MDA5, IPS-1, and TRAF3) but does not counteract its activation by IRF3. A detailed analysis revealed that the PEDV N protein targets TBK1 by direct interaction and that this binding sequesters the association between TBK1 and IRF3, which in turn inhibits both IRF3 activation and type I IFN production. Together, our findings demonstrate a new mechanism evolved by PEDV to circumvent the host's antiviral immunity. IMPORTANCE PEDV has received increasing attention since the emergence of a PEDV variant in China and the United States. Here, we identify nucleocapsid (N) protein as a novel PEDV-encoded interferon (IFN) antagonist and demonstrate that N protein antagonizes IFN production by sequestering the interaction between IRF3 and TBK1, a critical step in type I IFN signaling. This adds another layer of complexity to the immune evasion strategies evolved by this economically important viral pathogen. An understanding of its immune evasion mechanism may direct us to novel therapeutic targets and more effective vaccines against PEDV infection.",,"['Ding, Zhen', 'Fang, Liurong', 'Jing, Huiyuan', 'Zeng, Songlin', 'Wang, Dang', 'Liu, Lianzeng', 'Zhang, Huan', 'Luo, Rui', 'Chen, Huanchun', 'Xiao, Shaobo']",,,,
,PMC,Progression From IgD(+) IgM(+) to Isotype-Switched B Cells Is Site Specific during Coronavirus-Induced Encephalomyelitis,http://dx.doi.org/10.1128/JVI.00861-14,PMC4136247,,,"Various infections in the central nervous system (CNS) trigger B cell accumulation; however, the relative dynamics between viral replication and alterations in distinct B cell subsets are largely unknown. Using a glia-tropic coronavirus infection, which is initiated in the brain but rapidly spreads to and predominantly persists in the spinal cord, this study characterizes longitudinal changes in B cell subsets at both infected anatomical sites. The phase of T cell-dependent, antibody-independent control of infectious virus was associated with a similar recruitment of naive/early-activated IgD(+) IgM(+) B cells into both the brain and spinal cord. This population was progressively replaced by CD138(−) IgD(−) IgM(+) B cells, isotype-switched CD138(−) IgD(−) IgM(−) memory B cells (B(mem)), and CD138(+) antibody-secreting cells (ASC). A more rapid transition to B(mem) and ASC in spinal cord than in brain was associated with higher levels of persisting viral RNA and transcripts encoding factors promoting B cell migration, differentiation, and survival. The results demonstrate that naive/early-activated B cells are recruited early during coronavirus CNS infection but are subsequently replaced by more differentiated B cells. Furthermore, viral persistence, even at low levels, is a driving force for accumulation of isotype-switched B(mem) and ASC. IMPORTANCE Acute and chronic human CNS infections are associated with an accumulation of heterogeneous B cell subsets; however, their influence on viral load and disease is unclear. Using a glia-tropic coronavirus model, we demonstrate that the accumulation of B cells ranging from early-activated to isotype-switched differentiation stages is both temporally and spatially orchestrated. Acutely infected brains and spinal cords indiscriminately recruit a homogeneous population of early-activated B cells, which is progressively replaced by diverse, more differentiated subsets. The latter process is accelerated by elevated proinflammatory responses associated with viral persistence. The results imply that early-recruited B cells do not have antiviral function but may contribute to the inflammatory environment or act as antigen-presenting cells. Moreover, CNS viral persistence is a driving force promoting differentiated B cells with protective potential.",,"['Phares, Timothy W.', 'DiSano, Krista D.', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.']",,,,
,PMC,Functional Analyses of the Three Simian Hemorrhagic Fever Virus Nonstructural Protein 1 Papain-Like Proteases,http://dx.doi.org/10.1128/JVI.01020-14,PMC4136243,,,"The N-terminal region of simian hemorrhagic fever virus (SHFV) nonstructural polyprotein 1a is predicted to encode three papain-like proteases (PLP1α, PLP1β, and PLP1γ). Catalytic residues and cleavage sites for each of the SHFV PLP1s were predicted by alignment of the SHFV PLP1 region sequences with each other as well as with those of other arteriviruses, and the predicted catalytic residues were shown to be proximal by homology modeling of the SHFV nsp1s on porcine respiratory and reproductive syndrome virus (PRRSV) nsp1 crystal structures. The functionality of the predicted catalytic Cys residues and cleavage sites was tested by analysis of the autoproteolytic products generated in in vitro transcription/translation reactions done with wild-type or mutant SHFV nsp1 constructs. Cleavage sites were also analyzed by mass spectroscopy analysis of selected immunoprecipitated cleavage products. The data showed that each of the three SHFV PLP1s is an active protease. Cys63 was identified as the catalytic Cys of SHFV PLP1α and is adjacent to an Ala instead of the canonical Tyr observed in other arterivirus PLP1s. SHFV PLP1γ is able to cleave at both downstream and upstream nsp1 junction sites. Although intermediate precursor polyproteins as well as alternative products generated by each of the SHFV PLP1s cleaving at sites within the N-terminal region of nsp1β were produced in the in vitro reactions, Western blotting of SHFV-infected, MA104 cell lysates with SHFV nsp1 protein-specific antibodies detected only the three mature nsp1 proteins. IMPORTANCE SHFV is unique among arteriviruses in having three N-terminal papain-like protease 1 (PLP1) domains. Other arteriviruses encode one or two active PLP1s. This is the first functional study of the SHFV PLP1s. Analysis of the products of in vitro autoprocessing of an N-terminal SHFV nonstructural 1a polypeptide fragment showed that each of the three SHFV PLP1s is active, and the predicted catalytic Cys residues and cleavage sites for each PLP1 were confirmed by testing mutant constructs. Several unique features of the SHFV PLP1s were discovered. The SHFV PLP1α catalytic Cys63 is unique among arterivirus PLP1s in being adjacent to an Ala instead of a Trp. Other arterivirus PLP1s cleave only in cis at a single downstream site, but SHFV PLP1γ can cleave at both the downstream nsp1γ-nsp2 and upstream nsp1β-nsp1γ junctions. The three mature nsp1 proteins were produced both in the in vitro reactions and in infected cells.",,"['Vatter, Heather A.', 'Di, Han', 'Donaldson, Eric F.', 'Radu, Gertrud U.', 'Maines, Taronna R.', 'Brinton, Margo A.']",,,,
,PMC,Predicted Structure and Domain Organization of Rotavirus Capping Enzyme and Innate Immune Antagonist VP3,http://dx.doi.org/10.1128/JVI.00923-14,PMC4136241,,,"Rotaviruses and orbiviruses are nonturreted Reoviridae members. The rotavirus VP3 protein is a multifunctional capping enzyme and antagonist of the interferon-induced cellular oligoadenylate synthetase-RNase L pathway. Despite mediating important processes, VP3 is the sole protein component of the rotavirus virion whose structure remains unknown. In the current study, we used sequence alignment and homology modeling to identify features common to nonturreted Reoviridae capping enzymes and to predict the domain organization, structure, and active sites of rotavirus VP3. Our results suggest that orbivirus and rotavirus capping enzymes share a domain arrangement similar to that of the bluetongue virus capping enzyme. Sequence alignments revealed conserved motifs and suggested that rotavirus and orbivirus capping enzymes contain a variable N-terminal domain, a central guanine-N7-methyltransferase domain that contains an additional inserted domain, and a C-terminal guanylyltransferase and RNA 5′-triphosphatase domain. Sequence conservation and homology modeling suggested that the insertion in the guanine-N7-methyltransferase domain is a ribose-2′-O-methyltransferase domain for most rotavirus species. Our analyses permitted putative identification of rotavirus VP3 active-site residues, including those that form the ribose-2′-O-methyltransferase catalytic tetrad, interact with S-adenosyl-l-methionine, and contribute to autoguanylation. Previous reports have indicated that group A rotavirus VP3 contains a C-terminal 2H-phosphodiesterase domain that can cleave 2′-5′ oligoadenylates, thereby preventing RNase L activation. Our results suggest that a C-terminal phosphodiesterase domain is present in the capping enzymes from two additional rotavirus species. Together, these findings provide insight into a poorly understood area of rotavirus biology and are a springboard for future biochemical and structural studies of VP3. IMPORTANCE Rotaviruses are an important cause of severe diarrheal disease. The rotavirus VP3 protein caps viral mRNAs and helps combat cellular innate antiviral defenses, but little is known about its structure or enzymatic mechanisms. In this study, we used sequence- and structure-based alignments with related proteins to predict the structure of VP3 and identify enzymatic domains and active sites therein. This work provides insight into the mechanisms of rotavirus transcription and evasion of host innate immune defenses. An improved understanding of these processes may aid our ability to develop rotavirus vaccines and therapeutics.",,"['Ogden, Kristen M.', 'Snyder, Matthew J.', 'Dennis, Allison F.', 'Patton, John T.']",,,,
,PMC,Effects of Toll-Like Receptor Stimulation on Eosinophilic Infiltration in Lungs of BALB/c Mice Immunized with UV-Inactivated Severe Acute Respiratory Syndrome-Related Coronavirus Vaccine,http://dx.doi.org/10.1128/JVI.00983-14,PMC4135953,,,"Severe acute respiratory syndrome-related coronavirus (SARS-CoV) is an emerging pathogen that causes severe respiratory illness. Whole UV-inactivated SARS-CoV (UV-V), bearing multiple epitopes and proteins, is a candidate vaccine against this virus. However, whole inactivated SARS vaccine that includes nucleocapsid protein is reported to induce eosinophilic infiltration in mouse lungs after challenge with live SARS-CoV. In this study, an ability of Toll-like receptor (TLR) agonists to reduce the side effects of UV-V vaccination in a 6-month-old adult BALB/c mouse model was investigated, using the mouse-passaged Frankfurt 1 isolate of SARS-CoV. Immunization of adult mice with UV-V, with or without alum, resulted in partial protection from lethal doses of SARS-CoV challenge, but extensive eosinophil infiltration in the lungs was observed. In contrast, TLR agonists added to UV-V vaccine, including lipopolysaccharide, poly(U), and poly(I·C) (UV-V+TLR), strikingly reduced excess eosinophilic infiltration in the lungs and induced lower levels of interleukin-4 and -13 and eotaxin in the lungs than UV-V-immunization alone. Additionally, microarray analysis showed that genes associated with chemotaxis, eosinophil migration, eosinophilia, and cell movement and the polarization of Th2 cells were upregulated in UV-V-immunized but not in UV-V+TLR-immunized mice. In particular, CD11b(+) cells in the lungs of UV-V-immunized mice showed the upregulation of genes associated with the induction of eosinophils after challenge. These findings suggest that vaccine-induced eosinophil immunopathology in the lungs upon SARS-CoV infection could be avoided by the TLR agonist adjuvants. IMPORTANCE Inactivated whole severe acute respiratory syndrome-related coronavirus (SARS-CoV) vaccines induce neutralizing antibodies in mouse models; however, they also cause increased eosinophilic immunopathology in the lungs upon SARS-CoV challenge. In this study, the ability of adjuvant Toll-like receptor (TLR) agonists to reduce the side effects of UV-inactivated SARS-CoV vaccination in a BALB/c mouse model was tested, using the mouse-passaged Frankfurt 1 isolate of SARS-CoV. We found that TLR stimulation reduced the high level of eosinophilic infiltration that occurred in the lungs of mice immunized with UV-inactivated SARS-CoV. Microarray analysis revealed that genes associated with chemotaxis, eosinophil migration, eosinophilia, and cell movement and the polarization of Th2 cells were upregulated in UV-inactivated SARS-CoV-immunized mice. This study may be helpful for elucidating the pathogenesis underlying eosinophilic infiltration resulting from immunization with inactivated vaccine.",,"['Iwata-Yoshikawa, Naoko', 'Uda, Akihiko', 'Suzuki, Tadaki', 'Tsunetsugu-Yokota, Yasuko', 'Sato, Yuko', 'Morikawa, Shigeru', 'Tashiro, Masato', 'Sata, Tetsutaro', 'Hasegawa, Hideki', 'Nagata, Noriyo']",,,,
,PMC,Increased Mucosal CD4(+) T Cell Activation in Rhesus Macaques following Vaccination with an Adenoviral Vector,http://dx.doi.org/10.1128/JVI.03850-13,PMC4135938,,,"The possibility that vaccination with adenovirus (AdV) vectors increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of HIV acquisition within the Step trial. Modeling this within rhesus macaques is complicated because human adenoviruses, including human adenovirus type 5 (HAdV-5), are not endogenous to macaques. Here, we tested whether vaccination with a rhesus macaque-derived adenoviral vector (simian adenovirus 7 [SAdV-7]) enhances mucosal T cell activation within rhesus macaques. Following intramuscular SAdV-7 vaccination, we observed a pronounced increase in SAdV-7-specific CD4(+) T cell responses in peripheral blood and, more dramatically, in rectal mucosa tissue. Vaccination also induced a significant increase in the frequency of activated memory CD4(+) T cells in SAdV-7- and HAdV-5-vaccinated animals in the rectal mucosa but not in peripheral blood. These fluctuations within the rectal mucosa were also associated with a pronounced decrease in the relative frequency of naive resting CD4(+) T cells. Together, these results indicate that peripheral vaccination with an AdV vector can increase the activation of mucosal CD4(+) T cells, potentially providing an experimental model to further evaluate the role of host-vector interactions in increased HIV acquisition after AdV vector vaccination. IMPORTANCE The possibility that vaccination with a human adenovirus 5 vector increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of human immunodeficiency virus (HIV) acquisition within the Step trial. In this study, we tested whether vaccination with a rhesus macaque-derived adenoviral vector in rhesus macaques enhances mucosal CD4(+) T cell activation, the main cell target of simian immunodeficiency virus (SIV)/HIV. The results showed that vaccination with an adenoviral vector indeed increases activation of mucosal CD4(+) T cells and potentially increases susceptibility to SIV infection.",,"['Bukh, Irene', 'Calcedo, Roberto', 'Roy, Soumitra', 'Carnathan, Diane G.', 'Grant, Rebecca', 'Qin, Qiuyue', 'Boyd, Surina', 'Ratcliffe, Sarah J.', 'Veeder, Christin L.', 'Bellamy, Scarlett L.', 'Betts, Michael R.', 'Wilson, James M.']",,,,
,PMC,Inhibition of Arenavirus Infection by a Glycoprotein-Derived Peptide with a Novel Mechanism,http://dx.doi.org/10.1128/JVI.01133-14,PMC4135937,,,"The family Arenaviridae includes a number of viruses of public health importance, such as the category A hemorrhagic fever viruses Lassa virus, Junin virus, Machupo virus, Guanarito virus, and Sabia virus. Current chemotherapy for arenavirus infection is limited to the nucleoside analogue ribavirin, which is characterized by considerable toxicity and treatment failure. Using Pichinde virus as a model arenavirus, we attempted to design glycoprotein-derived fusion inhibitors similar to the FDA-approved anti-HIV peptide enfuvirtide. We have identified a GP2-derived peptide, AVP-p, with antiviral activity and no acute cytotoxicity. The 50% inhibitory dose (IC(50)) for the peptide is 7 μM, with complete inhibition of viral plaque formation at approximately 20 μM, and its antiviral activity is largely sequence dependent. AVP-p demonstrates activity against viruses with the Old and New World arenavirus viral glycoprotein complex but not against enveloped viruses of other families. Unexpectedly, fusion assays reveal that the peptide induces virus-liposome fusion at neutral pH and that the process is strictly glycoprotein mediated. As observed in cryo-electron micrographs, AVP-p treatment causes morphological changes consistent with fusion protein activation in virions, including the disappearance of prefusion glycoprotein spikes and increased particle diameters, and fluorescence microscopy shows reduced binding by peptide-treated virus. Steady-state fluorescence anisotropy measurements suggest that glycoproteins are destabilized by peptide-induced alterations in viral membrane order. We conclude that untimely deployment of fusion machinery by the peptide could render virions less able to engage in on-pathway receptor binding or endosomal fusion. AVP-p may represent a potent, highly specific, novel therapeutic strategy for arenavirus infection. IMPORTANCE Because the only drug available to combat infection by Lassa virus, a highly pathogenic arenavirus, is toxic and prone to treatment failure, we identified a peptide, AVP-p, derived from the fusion glycoprotein of a nonpathogenic model arenavirus, which demonstrates antiviral activity and no acute cytotoxicity. AVP-p is unique among self-derived inhibitory peptides in that it shows broad, specific activity against pseudoviruses bearing Old and New World arenavirus glycoproteins but not against viruses from other families. Further, the peptide's mechanism of action is highly novel. Biochemical assays and cryo-electron microscopy indicate that AVP-p induces premature activation of viral fusion proteins through membrane perturbance. Peptide treatment, however, does not increase the infectivity of cell-bound virus. We hypothesize that prematurely activated virions are less fit for receptor binding and membrane fusion and that AVP-p may represent a viable therapeutic strategy for arenavirus infection.",,"['Spence, Jennifer S.', 'Melnik, Lilia I.', 'Badani, Hussain', 'Wimley, William C.', 'Garry, Robert F.']",,,,
,PMC,Influenza A Virus-Induced Degradation of Eukaryotic Translation Initiation Factor 4B Contributes to Viral Replication by Suppressing IFITM3 Protein Expression,http://dx.doi.org/10.1128/JVI.00126-14,PMC4135930,,,"Although alteration in host cellular translation machinery occurs in virus-infected cells, the role of such alteration and the precise pathogenic processes are not well understood. Influenza A virus (IAV) infection shuts off host cell gene expression at transcriptional and translational levels. Here, we found that the protein level of eukaryotic translation initiation factor 4B (eIF4B), an integral component of the translation initiation apparatus, was dramatically reduced in A549 cells as well as in the lung, spleen, and thymus of mice infected with IAV. The decrease in eIF4B level was attributed to lysosomal degradation of eIF4B, which was induced by viral NS1 protein. Silencing eIF4B expression in A549 cells significantly promoted IAV replication, and conversely, overexpression of eIF4B markedly inhibited the viral replication. Importantly, we observed that eIF4B knockdown transgenic mice were more susceptible to IAV infection, exhibiting faster weight loss, shorter survival time, and more-severe organ damage. Furthermore, we demonstrated that eIF4B regulated the expression of interferon-induced transmembrane protein 3 (IFITM3), a critical protein involved in immune defense against a variety of RNA viruses, including influenza virus. Taken together, our findings reveal that eIF4B plays an important role in host defense against IAV infection at least by regulating the expression of IFITM3, which restricts viral entry and thereby blocks early stages of viral production. These data also indicate that influenza virus has evolved a strategy to overcome host innate immunity by downregulating eIF4B protein. IMPORTANCE Influenza A virus (IAV) infection stimulates the host innate immune system, in part, by inducing interferons (IFNs). Secreted IFNs activate the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, leading to elevated transcription of a large group of IFN-stimulated genes that have antiviral function. To circumvent the host innate immune response, influenza virus has evolved multiple strategies for suppressing the production of IFNs. Here, we show that IAV infection induces lysosomal degradation of eIF4B protein; and eIF4B inhibits IAV replication by upregulating expression of interferon-induced transmembrane protein 3 (IFITM3), a key protein that protects the host from virus infection. Our finding illustrates a critical role of eIF4B in the host innate immune response and provides novel insights into the complex mechanisms by which influenza virus interacts with its host.",,"['Wang, Song', 'Chi, Xiaojuan', 'Wei, Haitao', 'Chen, Yuhai', 'Chen, Zhilong', 'Huang, Shile', 'Chen, Ji-Long']",,,,
,PMC,Single-Domain Antibodies Targeting Neuraminidase Protect against an H5N1 Influenza Virus Challenge,http://dx.doi.org/10.1128/JVI.03178-13,PMC4135927,,,"Influenza virus neuraminidase (NA) is an interesting target of small-molecule antiviral drugs. We isolated a set of H5N1 NA-specific single-domain antibodies (N1-VHHm) and evaluated their in vitro and in vivo antiviral potential. Two of them inhibited the NA activity and in vitro replication of clade 1 and 2 H5N1 viruses. We then generated bivalent derivatives of N1-VHHm by two methods. First, we made N1-VHHb by genetically joining two N1-VHHm moieties with a flexible linker. Second, bivalent N1-VHH-Fc proteins were obtained by genetic fusion of the N1-VHHm moiety with the crystallizable region of mouse IgG2a (Fc). The in vitro antiviral potency against H5N1 of both bivalent N1-VHHb formats was 30- to 240-fold higher than that of their monovalent counterparts, with 50% inhibitory concentrations in the low nanomolar range. Moreover, single-dose prophylactic treatment with bivalent N1-VHHb or N1-VHH-Fc protected BALB/c mice against a lethal challenge with H5N1 virus, including an oseltamivir-resistant H5N1 variant. Surprisingly, an N1-VHH-Fc fusion without in vitro NA-inhibitory or antiviral activity also protected mice against an H5N1 challenge. Virus escape selection experiments indicated that one amino acid residue close to the catalytic site is required for N1-VHHm binding. We conclude that single-domain antibodies directed against influenza virus NA protect against H5N1 virus infection, and when engineered with a conventional Fc domain, they can do so in the absence of detectable NA-inhibitory activity. IMPORTANCE Highly pathogenic H5N1 viruses are a zoonotic threat. Outbreaks of avian influenza caused by these viruses occur in many parts of the world and are associated with tremendous economic loss, and these viruses can cause very severe disease in humans. In such cases, small-molecule inhibitors of the viral NA are among the few treatment options for patients. However, treatment with such drugs often results in the emergence of resistant viruses. Here we show that single-domain antibody fragments that are specific for NA can bind and inhibit H5N1 viruses in vitro and can protect laboratory mice against a challenge with an H5N1 virus, including an oseltamivir-resistant virus. In addition, plant-produced VHH fused to a conventional Fc domain can protect in vivo even in the absence of NA-inhibitory activity. Thus, NA of influenza virus can be effectively targeted by single-domain antibody fragments, which are amenable to further engineering.",,"['Cardoso, Francisco Miguel', 'Ibañez, Lorena Itatí', 'Van den Hoecke, Silvie', 'De Baets, Sarah', 'Smet, Anouk', 'Roose, Kenny', 'Schepens, Bert', 'Descamps, Francis J.', 'Fiers, Walter', 'Muyldermans, Serge', 'Depicker, Ann', 'Saelens, Xavier']",,,,
,PMC,Building and Sustaining a Regional Health Research and Innovation Network in Southeast Asia(),,PMC4375250,,,,,"MONTOYA, Jaime C.",,,,
,PMC,Identification of B Cell Epitopes in the MSG1 Protein of Mycoplasma suis,http://dx.doi.org/10.1089/mab.2014.0002,PMC4151056,,,"Mycoplasma suis (M. suis) is an extracellular bacterial organism that attaches to and causes deformity and damage to porcine red blood cells. M. suis glyceraldehyde-3-phosphate dehydrogenase-like protein 1 (MSG1), a membrane-associated adhesion protein, plays a major role in M. suis attachment and infection of porcine erythrocytes. In order to identify the epitopes in MSG1 protein of M. suis, recombinant MSG1 (rMSG1) expressed in Escherichia coli Top10 was purified with affinity chromatography and used to immunize BALB/c mice to prepare and screen monoclonal antibodies (MAbs). Western blot results showed that 1C10, 2F10, 4G10, and 10E9 can specifically react with recombinant MSG1 and M. suis. Moreover, 23 truncated fragments of MSG1 were amplified and cloned into pET-32a vector and induced by IPTG. Different recombinant truncated proteins were used to identify B cell epitopes in the rMSG1 protein. Epitope mapping revealed that MAb 1C10 recognizes the linear epitope D(291)THGSVF(297); MAb 2F10 recognizes the linear epitope L(251)CLKI(255); and MAbs 4G10 and 10E9 recognize the linear epitope I(268)KDGENE(274). The alignment of MSG1 epitope sequences with that of different M. suis strains accessed on NCBI showed that one epitope is highly conserved in M. suis strains. This research is the first to examine the epitopes in MSG1 of M. suis and demonstrate the variations of epitopes.",,"['Chang, Chen', 'Zou, Yao', 'Li, Yufeng']",,,,
,PMC,Acute Bacterial Sinusitis Complicating Viral Upper Respiratory Tract Infection in Young Children,http://dx.doi.org/10.1097/INF.0000000000000278,PMC4165747,,,"BACKGROUND: Acute bacterial sinusitis (ABS) is a common complication of viral upper respiratory tract infections (URI). Clinical characteristics of URIs complicated by ABS in young children have not been well studied. METHODS: We identified ABS episodes in a prospective, longitudinal cohort study of 294 children (6 to 35 months of age at enrollment), who were followed-up for one year to capture all URI episodes and complications. At the initial URI visit seen by the study personnel (median day=4 from symptoms onset), nasopharyngeal samples were obtained for bacterial cultures and viral studies. RESULTS: Of 1295 documented URI episodes, 103 (8%) episodes (in 73 children) were complicated by ABS, 32 of which were concurrent with acute otitis media. The majority (72%) of ABS episodes were diagnosed based on persistent symptoms or a biphasic course. Average age at ABS diagnosis was 18.8±7.2 months; white children were more likely to have ABS episodes than blacks (p=0.01). Hispanic/Latino ethnicity (p<0.0001) was negatively associated, and adequate PCV-7 immunization status (p=0.001) appeared to increase the risk of ABS. Girls had more ABS episodes than boys (0.5±0.8 vs 0.3±0.6 episodes/year, respectively, p=0.03). Viruses were detected in 63% during the initial URI visit; rhinovirus detection was positively correlated with ABS risk (p=0.01). Bacterial cultures were positive in 82/83 (99%) available samples obtained at the initial URI visit; polymicrobial (56%), Moraxella catarrhalis (20%) and Streptococcus pneumoniae (10%) were the most common cultures. Presence of pathogenic bacteria overall and presence of M. catarrhalis during URI were positively correlated with the risk for ABS (p=0.04 for both). CONCLUSION: ABS complicates 8% of URI in young children. Girls have more frequent ABS episodes than boys. Presence of rhinovirus and M. catarrhalis during URI are positively correlated with the risk for ABS complication.",,"['Marom, Tal', 'Alvarez-Fernandez, Pedro E.', 'Jennings, Kristofer', 'Patel, Janak A.', 'McCormick, David P.', 'Chonmaitree, Tasnee']",,,,
,PMC,Building a stable RNA U-turn with a protonated cytidine,http://dx.doi.org/10.1261/rna.043083.113,PMC4105743,,,"The U-turn is a classical three-dimensional RNA folding motif first identified in the anticodon and T-loops of tRNAs. It also occurs frequently as a building block in other functional RNA structures in many different sequence and structural contexts. U-turns induce sharp changes in the direction of the RNA backbone and often conform to the 3-nt consensus sequence 5′-UNR-3′ (N = any nucleotide, R = purine). The canonical U-turn motif is stabilized by a hydrogen bond between the N3 imino group of the U residue and the 3′ phosphate group of the R residue as well as a hydrogen bond between the 2′-hydroxyl group of the uridine and the N7 nitrogen of the R residue. Here, we demonstrate that a protonated cytidine can functionally and structurally replace the uridine at the first position of the canonical U-turn motif in the apical loop of the neomycin riboswitch. Using NMR spectroscopy, we directly show that the N3 imino group of the protonated cytidine forms a hydrogen bond with the backbone phosphate 3′ from the third nucleotide of the U-turn analogously to the imino group of the uridine in the canonical motif. In addition, we compare the stability of the hydrogen bonds in the mutant U-turn motif to the wild type and describe the NMR signature of the C+-phosphate interaction. Our results have implications for the prediction of RNA structural motifs and suggest simple approaches for the experimental identification of hydrogen bonds between protonated C-imino groups and the phosphate backbone.",,"['Gottstein-Schmidtke, Sina R.', 'Duchardt-Ferner, Elke', 'Groher, Florian', 'Weigand, Julia E.', 'Gottstein, Daniel', 'Suess, Beatrix', 'Wöhnert, Jens']",,,,
,PMC,Computational design of protein antigens that interact with the CDR H3 loop of HIV broadly neutralizing antibody 2F5,http://dx.doi.org/10.1002/prot.24641,PMC4437801,,,"Rational design of proteins with novel binding specificities and increased affinity is one of the major goals of computational protein design. Epitope-scaffolds are a new class of antigens engineered by transplanting viral epitopes of pre-defined structure to protein scaffolds, or by building protein scaffolds around such epitopes. Epitope-scaffolds are of interest as vaccine components to attempt to elicit neutralizing antibodies targeting the specified epitope. In this study we developed a new computational protocol, MultiGraft Interface, that transplants epitopes but also designs additional scaffold features outside the epitope to enhance antibody-binding specificity and potentially influence the specificity of elicited antibodies. We employed MultiGraft Interface to engineer novel epitope-scaffolds that display the known epitope of HIV-1 neutralizing antibody 2F5 and that also interact with the functionally important CDR H3 antibody loop. MultiGraft Interface generated an epitope-scaffold that bound 2F5 with sub-nanomolar affinity (K(D) = 400 pM) and that interacted with the antibody CDR H3 loop through computationally designed contacts. Substantial structural modifications were necessary to engineer this antigen, with the 2F5 epitope replacing a helix in the native scaffold and with 15% of the native scaffold sequence being modified in the design stage. This epitope-scaffold represents a successful example of rational protein backbone engineering and protein-protein interface design and could prove useful in the field of HIV vaccine design. MultiGraft Interface can be generally applied to engineer novel binding partners with altered specificity and optimized affinity.",,"['Azoitei, M.L.', 'Ban, Y.A.', 'Kalyuzhny, O.', 'Guenaga, J.', 'Schroeter, A.', 'Porter, J.', 'Wyatt, R.', 'Schief, W.R.']",,,,
,PMC,"Coronavirus Nsp10, a Critical Co-factor for Activation of Multiple Replicative Enzymes",http://dx.doi.org/10.1074/jbc.M114.577353,PMC4162180,,,"The RNA-synthesizing machinery of the severe acute respiratory syndrome Coronavirus (SARS-CoV) is composed of 16 non-structural proteins (nsp1–16) encoded by ORF1a/1b. The 148-amino acid nsp10 subunit contains two zinc fingers and is known to interact with both nsp14 and nsp16, stimulating their respective 3′-5′ exoribonuclease and 2′-O-methyltransferase activities. Using alanine-scanning mutagenesis, in cellulo bioluminescence resonance energy transfer experiments, and in vitro pulldown assays, we have now identified the key residues on the nsp10 surface that interact with nsp14. The functional consequences of mutations introduced at these positions were first evaluated biochemically by monitoring nsp14 exoribonuclease activity. Disruption of the nsp10-nsp14 interaction abrogated the nsp10-driven activation of the nsp14 exoribonuclease. We further showed that the nsp10 surface interacting with nsp14 overlaps with the surface involved in the nsp10-mediated activation of nsp16 2′-O-methyltransferase activity, suggesting that nsp10 is a major regulator of SARS-CoV replicase function. In line with this notion, reverse genetics experiments supported an essential role of the nsp10 surface that interacts with nsp14 in SARS-CoV replication, as several mutations that abolished the interaction in vitro yielded a replication-negative viral phenotype. In contrast, mutants in which the nsp10-nsp16 interaction was disturbed proved to be crippled but viable. These experiments imply that the nsp10 surface that interacts with nsp14 and nsp16 and possibly other subunits of the viral replication complex may be a target for the development of antiviral compounds against pathogenic coronaviruses.",,"['Bouvet, Mickaël', 'Lugari, Adrien', 'Posthuma, Clara C.', 'Zevenhoven, Jessika C.', 'Bernard, Stéphanie', 'Betzi, Stéphane', 'Imbert, Isabelle', 'Canard, Bruno', 'Guillemot, Jean-Claude', 'Lécine, Patrick', 'Pfefferle, Susanne', 'Drosten, Christian', 'Snijder, Eric J.', 'Decroly, Etienne', 'Morelli, Xavier']",,,,
,PMC,Dimeric Switch of Hakai-truncated Monomers during Substrate Recognition: INSIGHTS FROM SOLUTION STUDIES AND NMR STRUCTURE,http://dx.doi.org/10.1074/jbc.M114.592840,PMC4162166,,,"Hakai, an E3 ubiquitin ligase, disrupts cell-cell contacts in epithelial cells and is up-regulated in human colon and gastric adenocarcinomas. Hakai acts through its phosphotyrosine-binding (HYB) domain, which bears a dimeric fold that recognizes the phosphotyrosine motifs of E-cadherin, cortactin, DOK1, and other Src substrates. Unlike the monomeric nature of the SH2 and phosphotyrosine-binding domains, the architecture of the HYB domain consists of an atypical, zinc-coordinated tight homodimer. Here, we report a C-terminal truncation mutant of the HYB domain (HYB(ΔC)), comprising amino acids 106–194, which exists as a monomer in solution. The NMR structure revealed that this deletion mutant undergoes a dramatic structural change caused by a rearrangement of the atypical zinc-coordinated unit in the C terminus of the HYB domain to a C(2)H(2)-like zinc finger in HYB(ΔC). Moreover, using isothermal titration calorimetry, we show that dimerization of HYB(ΔC) can be induced using a phosphotyrosine substrate peptide. This ligand-induced dimerization of HYB(ΔC) is further validated using analytical ultracentrifugation, size-exclusion chromatography, NMR relaxation studies, dynamic light scattering, and circular dichroism experiments. Overall, these observations suggest that the dimeric architecture of the HYB domain is essential for the phosphotyrosine-binding property of Hakai.",,"['Mukherjee, Manjeet', 'Jing-Song, Fan', 'Ramachandran, Sarath', 'Guy, Graeme R.', 'Sivaraman, J.']",,,,
,PMC,Recombinant myxoma virus lacking all poxvirus ankyrin-repeat proteins stimulates multiple cellular anti-viral pathways and exhibits a severe decrease in virulence,http://dx.doi.org/10.1016/j.virol.2014.06.021,PMC4157118,,,"Although the production of single gene knockout viruses is a useful strategy to study viral gene functions, the redundancy of many host interactive genes within a complex viral genome can obscure their collective functions. In this study, a rabbit-specific poxvirus, myxoma virus (MYXV), was genetically altered to disrupt multiple members of the poxviral ankyrin-repeat (ANK-R) protein superfamily, M-T5, M148, M149 and M150. A particularly robust activation of the NF-κB pathway was observed in A549 cells following infection with the complete ANK-R knockout (vMyx-ANKsKO). Also, an increased release of IL-6 was only observed upon infection with vMyx-ANKsKO. In virus-infected rabbit studies, vMyx-ANKsKO was the most extensively attenuated and produced the smallest primary lesion of all ANK-R mutant constructs. This study provides the first insights into the shared functions of the poxviral ANK-R protein superfamily in vitro and in vivo.",,"['Lamb, Stephanie A.', 'Rahman, Masmudur M.', 'McFadden, Grant']",,,,
,PMC,A Smad3 and TTF-1/NKX2-1 complex regulates Smad4-independent gene expression,http://dx.doi.org/10.1038/cr.2014.97,PMC4123303,,,"Thyroid transcription factor-1 (TTF-1, also known as NKX2-1) is a tissue-specific transcription factor in lung epithelial cells. Although TTF-1 inhibits the epithelial-to-mesenchymal transition induced by transforming growth factor-β (TGF-β) in lung adenocarcinoma cells, the mechanism through which TTF-1 inhibits the functions of TGF-β is unknown. Here we show that TTF-1 disrupts the nuclear Smad3-Smad4 complex without affecting the nuclear localization of phospho-Smad3. Genome-wide analysis by chromatin immunoprecipitation followed by sequencing revealed that TTF-1 colocalizes with Smad3 on chromatin and alters Smad3-binding patterns throughout the genome, while TTF-1 generally inhibits Smad4 binding to chromatin. Moreover, Smad3 binds to chromatin together with TTF-1, but not with Smad4, at some Smad3-binding regions when TGF-β signaling is absent, and knockdown of Smad4 expression does not attenuate Smad3 binding in these regions. Thus, TTF-1 may compete with Smad4 for interaction with Smad3, and in the presence of TTF-1, Smad3 regulates the transcription of certain genes independently of Smad4. These findings provide a new model of regulation of TGF-β-Smad signaling by TTF-1.",,"['Isogaya, Kazunobu', 'Koinuma, Daizo', 'Tsutsumi, Shuichi', 'Saito, Roy-Akira', 'Miyazawa, Keiji', 'Aburatani, Hiroyuki', 'Miyazono, Kohei']",,,,
,PMC,High frequency of cytolytic 21-Hydroxylase specific CD8(+) T cells in autoimmune Addison’s disease patients(),http://dx.doi.org/10.4049/jimmunol.1400056,PMC4821366,,,"The mechanisms behind the destruction of the adrenal glands in autoimmune Addison’s disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in over 90% of patients, but these autoantibodies are not thought to mediate the disease. Here we demonstrate highly frequent 21-hydroxylase specific T cells detectable in 20 patients with Addison’s disease. Using overlapping 18aa peptides spanning the full length of 21-hydroxylase, we identified immunodominant CD8(+) and CD4(+) T cell responses in a large proportion of Addison’s patients both ex-vivo and after in-vitro culture of peripheral blood lymphocytes up to 20 years after diagnosis. In a large proportion of patients, CD8(+) 21-hydroxylase specific T cells and CD4(+) 21-hydroxylase specific T cells were very abundant and detectable in ex-vivo assays. HLA class-I tetramer-guided isolation of 21-hydroxylase specific CD8(+) T cells showed their ability to lyse 21-hydroxylase positive target cells, consistent with a potential mechanism for disease pathogenesis. These data indicate strong cytotoxic T lymphocyte responses to 21-hydroxylase often occur in-vivo, and that reactive cytotoxic T lymphocytes have substantial proliferative and cytolytic potential. These results have implications for earlier diagnosis of adrenal failure and ultimately a potential target for therapeutic intervention and induction of immunity against adrenal cortex cancer.",,"['Dawoodji, Amina', 'Chen, Ji-Li', 'Shepherd, Dawn', 'Dalin, Frida', 'Tarlton, Andrea', 'Alimohammadi, Mohammad', 'Penna-Martinez, Marissa', 'Meyer, Gesine', 'Mitchell, Anna L', 'Gan, Earn H', 'Bratland, Eirik', 'Bensing, Sophie', 'Husebye, Eystein', 'Pearce, Simon H.', 'Badenhoop, Klaus', 'Kämpe, Olle', 'Cerundolo, Vincenzo']",,,,
,PMC,Knockdown of Drosha in human alveolar type II cells alters expression of SP-A in culture: a pilot study,http://dx.doi.org/10.3109/01902148.2014.929757,PMC4197128,,,"Human surfactant protein A (SP-A) plays an important role in surfactant metabolism and lung innate immunity. SP-A is synthesized and secreted by alveolar type II cells (ATII), one of the two cell types of the distal lung epithelium (ATII and ATI). We have shown that miRNA interactions with sequence polymorphisms on the SP-A mRNA 3′UTRs mediate differential expression of SP-A1 and SP-A2 gene variants in vitro. In the present study, we describe a physiologically relevant model to study miRNA regulation of SP-A in human ATII. For these studies, we purified and cultured human ATII on an air-liquid interface matrix (A/L) or plastic wells without matrix (P). Gene expression analyses confirmed that cells cultured in A/L maintained the ATII phenotype for over 5 days, whereas P-cultured cells differentiated to ATI. When we transfected ATII with siRNAs to inhibit the expression of Drosha, a critical effector of miRNA maturation, the levels of SP-A mRNA and protein increased in a time dependent manner. We next characterized cultured ATII and ATI by studying expression of 1,066 human miRNAs using miRNA PCR arrays. We detected expression of >300 miRNAs with 24 miRNAs differentially expressed in ATII vs. ATI, 12 of which predicted to bind SP-A 3′UTRs, indicating that these may be implicated in SP-A downregulation in ATI. Thus, miRNAs not only affect SPA expression, but also may contribute to the maintenance of the ATII cell phenotype and/or the trans-differentiation of ATII to ATI cells, and may represent new molecular markers that distinguish ATII and ATI.",,"['Silveyra, Patricia', 'Chroneos, Zissis C', 'DiAngelo, Susan L', 'Thomas, Neal J', 'Noutsios, Georgios T', 'Tsotakos, Nikolaos', 'Howrlylak, Judie A', 'Umstead, Todd M', 'Floros, Joanna']",,,,
,PMC,Crystallization and preliminary crystallographic study of human coronavirus NL63 main protease in complex with an inhibitor,http://dx.doi.org/10.1107/S2053230X14012953,PMC4118806,,,"Human coronavirus NL63 mainly infects younger children and causes cough, fever, rhinorrhoea, bronchiolitis and croup. It encodes two polyprotein precursors required for genome replication and transcription. Each polyprotein undergoes extensive proteolytic processing, resulting in functional subunits. This process is mainly mediated by its genome-encoded main protease, which is an attractive target for antiviral drug design. In this study, the main protease of human coronavirus NL63 was crystallized in complex with a Michael acceptor. The complex crystals diffracted to 2.85 Å resolution and belonged to space group P4(1)2(1)2, with unit-cell parameters a = b = 87.2, c = 212.1 Å. Two molecules were identified per asymmetric unit.",,"['Wang, Fenghua', 'Tan, Yusheng', 'Li, Huiyan', 'Chen, Xia', 'Wang, Jinshan', 'Li, Shuang', 'Fu, Sheng', 'Zhao, Qi', 'Chen, Cheng', 'Su, Dan', 'Yang, Haitao']",,,,
,PMC,An infectious bat chimeric influenza virus harboring the entry machinery of a influenza A virus,http://dx.doi.org/10.1038/ncomms5448,PMC5533278,,,"In 2012 the complete genomic sequence of a new and potentially harmful influenza A-like virus from bats (H17N10) was identified. However, infectious influenza virus was neither isolated from infected bats nor reconstituted, impeding further characterization of this virus. Here we show the generation of an infectious chimeric virus containing six out of the eight bat virus genes, with the remaining two genes encoding the HA and NA proteins of a prototypic influenza A virus. This engineered virus replicates well in a broad range of mammalian cell cultures, human primary airway epithelial cells and mice, but poorly in avian cells and chicken embryos without further adaptation. Importantly, the bat chimeric virus is unable to reassort with other influenza A viruses. Although our data do not exclude the possibility of zoonotic transmission of bat influenza viruses into the human population, they indicate that multiple barriers exist that makes this an unlikely event.",,"['Juozapaitis, Mindaugas', 'Moreira, Étori Aguiar', 'Mena, Ignacio', 'Giese, Sebastian', 'Riegger, David', 'Pohlmann, Anne', 'Höper, Dirk', 'Zimmer, Gert', 'Beer, Martin', 'García-Sastre, Adolfo', 'Schwemmle, Martin']",,,,
,PMC,Discovery of novel aromatase inhibitors using a homogeneous time-resolved fluorescence assay,http://dx.doi.org/10.1038/aps.2014.53,PMC4125720,,,"AIM: Aromatase is an important target for drugs to treat hormone-dependent diseases, including breast cancer. The aim of this study was to develop a homogeneous time-resolved fluorescence (HTRF) aromatase assay suitable for high-throughput screening (HTS). METHODS: A 384-well aromatase HTRF assay was established, and used to screen about 7000 compounds from a compound library. Anti-proliferation activity of the hit was evaluated using alamarBlue(R) assay in a hormone-dependent breast cancer cell line T47D. Molecular docking was conducted to elucidate the binding mode of the hit using the Discovery Studio program. RESULTS: The Z′ value and signal to background (S/B) ratio were 0.74 and 5.4, respectively. Among the 7000 compounds, 4 hits (XHN22, XHN26, XHN27 and triptoquinone A) were found to inhibit aromatase with IC(50) values of 1.60±0.07, 2.76±0.24, 0.81±0.08 and 45.8±11.3 μmol /L, respectively. The hits XHN22, XHN26 and XHN27 shared the same chemical scaffold of 4-imidazolyl quinoline. Moreover, the most potent hit XHN27 at 10 and 50 μmol/L inhibited the proliferation of T47D cells by 45.3% and 35.2%, respectively. The docking study revealed that XHN27 docked within the active site of aromatase and might form a hydrogen bond and had a π-cation interaction with amino acid residues of the protein. CONCLUSION: XHN27, an imidazolyl quinoline derivative of flavonoid, is a potent aromatase inhibitor with anti-proliferation activity against breast cancer in vitro. The established assay can be used in HTS for discovering novel aromatase inhibitor.",,"['Ji, Jin-zi', 'Lao, Ke-jing', 'Hu, Jie', 'Pang, Tao', 'Jiang, Zhen-zhou', 'Yuan, Hao-liang', 'Miao, Jing-shan', 'Chen, Xin', 'Ning, Shan-shan', 'Xiang, Hua', 'Guo, Yu-meng', 'Yan, Ming', 'Zhang, Lu-yong']",,,,
,PMC,Structure of the eukaryotic translation initiation factor eIF4E in complex with 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G,http://dx.doi.org/10.1073/pnas.1410250111,PMC4128100,,,"The interaction of the eukaryotic translation initiation factor eIF4E with the initiation factor eIF4G recruits the 40S ribosomal particle to the 5′ end of mRNAs, facilitates scanning to the AUG start codon, and is crucial for eukaryotic translation of nearly all genes. Efficient recruitment of the 40S particle is particularly important for translation of mRNAs encoding oncoproteins and growth-promoting factors, which often harbor complex 5′ UTRs and require efficient initiation. Thus, inhibiting the eIF4E/eIF4G interaction has emerged as a previously unpursued route for developing anticancer agents. Indeed, we discovered small-molecule inhibitors of this eIF4E/eIF4G interaction (4EGIs) that inhibit translation initiation both in vitro and in vivo and were used successfully in numerous cancer–biology and neurobiology studies. However, their detailed molecular mechanism of action has remained elusive. Here, we show that the eIF4E/eIF4G inhibitor 4EGI-1 acts allosterically by binding to a site on eIF4E distant from the eIF4G binding epitope. Data from NMR mapping and high-resolution crystal structures are congruent with this mechanism, where 4EGI-1 attaches to a hydrophobic pocket of eIF4E between β-sheet(2) (L(60)-T(68)) and α-helix(1) (E(69)-N(77)), causing localized conformational changes mainly in the H(78)-L(85) region. It acts by unfolding a short 3(10)-helix (S(82)-L(85)) while extending α-helix(1) by one turn (H(78)-S(82)). This unusual helix rearrangement has not been seen in any previous eIF4E structure and reveals elements of an allosteric inhibition mechanism leading to the dislocation of eIF4G from eIF4E.",,"['Papadopoulos, Evangelos', 'Jenni, Simon', 'Kabha, Eihab', 'Takrouri, Khuloud J.', 'Yi, Tingfang', 'Salvi, Nicola', 'Luna, Rafael E.', 'Gavathiotis, Evripidis', 'Mahalingam, Poornachandran', 'Arthanari, Haribabu', 'Rodriguez-Mias, Ricard', 'Yefidoff-Freedman, Revital', 'Aktas, Bertal H.', 'Chorev, Michael', 'Halperin, Jose A.', 'Wagner, Gerhard']",,,,
,PMC,Pathogen Inactivation Technologies for Cellular Blood Components: an Update,http://dx.doi.org/10.1159/000365646,PMC4164100,,,"Nowadays patients receiving blood components are exposed to much less transfusion-transmitted infectious diseases than three decades before when among others HIV was identified as causative agent for the acquired immunodeficiency syndrome and the transmission by blood or coagulation factors became evident. Since that time the implementation of measures for risk prevention and safety precaution was socially and politically accepted. Currently emerging pathogens like arboviruses and the well-known bacterial contamination of platelet concentrates still remain major concerns of blood safety with important clinical consequences, but very rarely with fatal outcome for the blood recipient. In contrast to the well-established pathogen inactivation strategies for fresh frozen plasma using the solvent-detergent procedure or methylene blue and visible light, the bench-to-bedside translation of novel pathogen inactivation technologies for cell-containing blood components such as platelets and red blood cells are still underway. This review summarizes the pharmacological/toxicological assessment and the inactivation efficacy against viruses, bacteria, and protozoa of each of the currently available pathogen inactivation technologies and highlights the impact of the results obtained from several randomized clinical trials and hemovigilance data. Until now in some European countries pathogen inactivation technologies are in in routine use for single-donor plasma and platelets. The invention and adaption of pathogen inactivation technologies for red blood cell units and whole blood donations suggest the universal applicability of these technologies and foster a paradigm shift in the manufacturing of safe blood.",,"Schlenke, Peter",,,,
,PMC,Japanese encephalitis virus replication is negatively regulated by autophagy and occurs on LC3-I- and EDEM1-containing membranes,http://dx.doi.org/10.4161/auto.29455,PMC4206540,,,"Autophagy is a lysosomal degradative pathway that has diverse physiological functions and plays crucial roles in several viral infections. Here we examine the role of autophagy in the life cycle of JEV, a neurotropic flavivirus. JEV infection leads to induction of autophagy in several cell types. JEV replication was significantly enhanced in neuronal cells where autophagy was rendered dysfunctional by ATG7 depletion, and in Atg5-deficient mouse embryonic fibroblasts (MEFs), resulting in higher viral titers. Autophagy was functional during early stages of infection however it becomes dysfunctional as infection progressed resulting in accumulation of misfolded proteins. Autophagy-deficient cells were highly susceptible to virus-induced cell death. We also observed JEV replication complexes that are marked by nonstructural protein 1 (NS1) and dsRNA colocalized with endogenous LC3 but not with GFP-LC3. Colocalization of NS1 and LC3 was also observed in Atg5 deficient MEFs, which contain only the nonlipidated form of LC3. Viral replication complexes furthermore show association with a marker of the ER-associated degradation (ERAD) pathway, EDEM1 (ER degradation enhancer, mannosidase α-like 1). Our data suggest that virus replication occurs on ERAD-derived EDEM1 and LC3-I-positive structures referred to as EDEMosomes. While silencing of ERAD regulators EDEM1 and SEL1L suppressed JEV replication, LC3 depletion exerted a profound inhibition with significantly reduced RNA levels and virus titers. Our study suggests that while autophagy is primarily antiviral for JEV and might have implications for disease progression and pathogenesis of JEV, nonlipidated LC3 plays an important autophagy independent function in the virus life cycle.",,"['Sharma, Manish', 'Bhattacharyya, Sankar', 'Nain, Minu', 'Kaur, Manpreet', 'Sood, Vikas', 'Gupta, Vishal', 'Khasa, Renu', 'Abdin, Malik Z', 'Vrati, Sudhanshu', 'Kalia, Manjula']",,,,
,PMC,ACE for all – a molecular perspective,http://dx.doi.org/10.1007/s12079-014-0236-8,PMC4165820,,,"Angiotensin-I converting enzyme (ACE, EC 3.4.15.1) is a zinc dependent dipeptidyl carboxypeptidase with an essential role in mammalian blood pressure regulation as part of the renin-angiotensin aldosterone system (RAAS). As such, it has long been targeted in the treatment of hypertension through the use of ACE inhibitors. Although ACE has been studied since the 1950s, only recently have the full range of functions of this enzyme begun to truly be appreciated. ACE homologues have been found in a host of other organisms, and are now known to be conserved in insects. Insect ACE homologues typically share over 30 % amino acid sequence identity with human ACE. Given that insects lack a mammalian type circulatory system, they must have crucial roles in other physiological processes. The first ACE crystal structures were reported during the last decade and have enabled these enzymes to be studied from an entirely different perspective. Here we review many of these key developments and the implications that they have had on our understanding of the diverse functions of these enzymes. Specifically, we consider how structural information is being used in the design of a new generation of ACE inhibitors with increased specificity, and how the structures of ACE homologues are related to their functions. The Anopheles gambiae genome is predicted to code for ten ACE homologues, more than any genome studied so far. We have modelled the active sites of some of these as yet uncharacterised enzymes to try and infer more about their potential roles at the molecular level.",,"['Harrison, Charlotte', 'Acharya, K. Ravi']",,,,
,PMC,The Effect of Inhaled IFN-β on Worsening of Asthma Symptoms Caused by Viral Infections. A Randomized Trial,http://dx.doi.org/10.1164/rccm.201312-2235OC,PMC4226052,,,"Rationale: Ex vivo, bronchial epithelial cells from people with asthma are more susceptible to rhinovirus infection caused by deficient induction of the antiviral protein, IFN-β. Exogenous IFN-β restores antiviral activity. Objectives: To compare the efficacy and safety of inhaled IFN-β with placebo administered to people with asthma after onset of cold symptoms to prevent or attenuate asthma symptoms caused by respiratory viruses. Methods: A total of 147 people with asthma on inhaled corticosteroids (British Thoracic Society Steps 2–5), with a history of virus-associated exacerbations, were randomized to 14-day treatment with inhaled IFN-β (n = 72) or placebo (n = 75) within 24 hours of developing cold symptoms and were assessed clinically, with relevant samples collected to assess virus infection and antiviral responses. Measurements and Main Results: A total of 91% of randomized patients developed a defined cold. In this modified intention-to-treat population, asthma symptoms did not get clinically significantly worse (mean change in six-item Asthma Control Questionnaire <0.5) and IFN-β treatment had no significant effect on this primary endpoint, although it enhanced morning peak expiratory flow recovery (P = 0.033), reduced the need for additional treatment, and boosted innate immunity as assessed by blood and sputum biomarkers. In an exploratory analysis of the subset of more difficult-to-treat, Step 4-5 people with asthma (n = 27 IFN-β; n = 31 placebo), Asthma Control Questionnaire-6 increased significantly on placebo; this was prevented by IFN-β (P = 0.004). Conclusions: Although the trial did not meet its primary endpoint, it suggests that inhaled IFN-β is a potential treatment for virus-induced deteriorations of asthma in difficult-to-treat people with asthma and supports the need for further, adequately powered, trials in this population. Clinical trial registered with www.clinicaltrials.gov (NCT 01126177).",,"['Djukanović, Ratko', 'Harrison, Tim', 'Johnston, Sebastian L.', 'Gabbay, Flic', 'Wark, Peter', 'Thomson, Neil C.', 'Niven, Robert', 'Singh, Dave', 'Reddel, Helen K.', 'Davies, Donna E.', 'Marsden, Richard', 'Boxall, Christine', 'Dudley, Sarah', 'Plagnol, Vincent', 'Holgate, Stephen T.', 'Monk, Phillip']",,,,
,PMC,Respiratory Syncytial Virus Increases the Virulence of Streptococcus pneumoniae by Binding to Penicillin Binding Protein 1a. A New Paradigm in Respiratory Infection,http://dx.doi.org/10.1164/rccm.201311-2110OC,PMC4226051,,,"Rationale: Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are major respiratory pathogens. Coinfection with RSV and S. pneumoniae is associated with severe and often fatal pneumonia but the molecular basis for this remains unclear. Objectives: To determine if interaction between RSV and pneumococci enhances pneumococcal virulence. Methods: We used confocal microscopy and Western blot to identify the receptors involved in direct binding of RSV and pneumococci, the effects of which were studied in both in vivo and in vitro models of infection. Human ciliated respiratory epithelial cell cultures were infected with RSV for 72 hours and then challenged with pneumococci. Pneumococci were collected after 2 hours exposure and changes in gene expression determined using quantitative real-time polymerase chain reaction. Measurements and Main Results: Following incubation with RSV or purified G protein, pneumococci demonstrated a significant increase in the inflammatory response and bacterial adherence to human ciliated epithelial cultures and markedly increased virulence in a pneumonia model in mice. This was associated with extensive changes in the pneumococcal transcriptome and significant up-regulation in the expression of key pneumococcal virulence genes, including the gene for the pneumococcal toxin, pneumolysin. We show that mechanistically this is caused by RSV G glycoprotein binding penicillin binding protein 1a. Conclusions: The direct interaction between a respiratory virus protein and the pneumococcus resulting in increased bacterial virulence and worsening disease outcome is a new paradigm in respiratory infection.",,"['Smith, Claire M.', 'Sandrini, Sara', 'Datta, Sumit', 'Freestone, Primrose', 'Shafeeq, Sulman', 'Radhakrishnan, Priya', 'Williams, Gwyneth', 'Glenn, Sarah M.', 'Kuipers, Oscar P.', 'Hirst, Robert A.', 'Easton, Andrew J.', 'Andrew, Peter W.', 'O’Callaghan, Christopher']",,,,
,PMC,The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology,http://dx.doi.org/10.1146/annurev-virology-031413-085527,PMC6889812,,,"In recent years, mass spectrometry has emerged as a core component of fundamental discoveries in virology. As a consequence of their coevolution, viruses and host cells have established complex, dynamic interactions that function either in promoting virus replication and dissemination or in host defense against invading pathogens. Thus, viral infection triggers an impressive range of proteome changes. Alterations in protein abundances, interactions, posttranslational modifications, subcellular localizations, and secretion are temporally regulated during the progression of an infection. Consequently, understanding viral infection at the molecular level requires versatile approaches that afford both breadth and depth of analysis. Mass spectrometry is uniquely positioned to bridge this experimental dichotomy. Its application to both unbiased systems analyses and targeted, hypothesis-driven studies has accelerated discoveries in viral pathogenesis and host defense. Here, we review the contributions of mass spectrometry–based proteomic approaches to understanding viral morphogenesis, replication, and assembly and to characterizing host responses to infection.",,"['Greco, Todd M.', 'Diner, Benjamin A.', 'Cristea, Ileana M.']",,,,
,PMC,Maternal vaccination: moving the science forward,http://dx.doi.org/10.1093/humupd/dmu041,PMC4255605,,,"BACKGROUND: Infections remain one of the leading causes of morbidity in pregnant women and newborns, with vaccine-preventable infections contributing significantly to the burden of disease. In the past decade, maternal vaccination has emerged as a promising public health strategy to prevent and combat maternal, fetal and neonatal infections. Despite a number of universally recommended maternal vaccines, the development and evaluation of safe and effective maternal vaccines and their wide acceptance are hampered by the lack of thorough understanding of the efficacy and safety in the pregnant women and the offspring. METHODS: An outline was synthesized based on the current status and major gaps in the knowledge of maternal vaccination. A systematic literature search in PUBMED was undertaken using the key words in each section title of the outline to retrieve articles relevant to pregnancy. Articles cited were selected based on relevance and quality. On the basis of the reviewed information, a perspective on the future directions of maternal vaccination research was formulated. RESULTS: Maternal vaccination can generate active immune protection in the mother and elicit systemic immunoglobulin G (IgG) and mucosal IgG, IgA and IgM responses to confer neonatal protection. The maternal immune system undergoes significant modulation during pregnancy, which influences responsiveness to vaccines. Significant gaps exist in our knowledge of the efficacy and safety of maternal vaccines, and no maternal vaccines against a large number of old and emerging pathogens are available. Public acceptance of maternal vaccination has been low. CONCLUSIONS: To tackle the scientific challenges of maternal vaccination and to provide the public with informed vaccination choices, scientists and clinicians in different disciplines must work closely and have a mechanistic understanding of the systemic, reproductive and mammary mucosal immune responses to vaccines. The use of animal models should be coupled with human studies in an iterative manner for maternal vaccine experimentation, evaluation and optimization. Systems biology approaches should be adopted to improve the speed, accuracy and safety of maternal vaccine targeting.",,"['Faucette, Azure N.', 'Unger, Benjamin L.', 'Gonik, Bernard', 'Chen, Kang']",,,,
,PMC,Molecular mechanisms regulating CD13-mediated adhesion,http://dx.doi.org/10.1111/imm.12279,PMC4107673,,,"CD13/Aminopeptidase N is a transmembrane metalloproteinase that is expressed in many tissues where it regulates various cellular functions. In inflammation, CD13 is expressed on myeloid cells, is up-regulated on endothelial cells at sites of inflammation and mediates monocyte/endothelial adhesion by homotypic interactions. In animal models the lack of CD13 alters the profiles of infiltrating inflammatory cells at sites of ischaemic injury. Here, we found that CD13 expression is enriched specifically on the pro-inflammatory subset of monocytes, suggesting that CD13 may regulate trafficking and function of specific subsets of immune cells. To further dissect the mechanisms regulating CD13-dependent trafficking we used the murine model of thioglycollate-induced sterile peritonitis. Peritoneal monocytes, macrophages and dendritic cells were significantly decreased in inflammatory exudates from global CD13(KO) animals when compared with wild-type controls. Furthermore, adoptive transfer of wild-type and CD13(KO) primary myeloid cells, or wild-type myeloid cells pre-treated with CD13-blocking antibodies into thioglycollate-challenged wild-type recipients demonstrated fewer CD13(KO) or treated cells in the lavage, suggesting that CD13 expression confers a competitive advantage in trafficking. Similarly, both wild-type and CD13(KO) cells were reduced in infiltrates in CD13(KO) recipients, confirming that both monocytic and endothelial CD13 contribute to trafficking. Finally, murine monocyte cell lines expressing mouse/human chimeric CD13 molecules demonstrated that the C-terminal domain of the protein mediates CD13 adhesion. Therefore, this work verifies that the altered inflammatory trafficking in CD13(KO) mice is the result of aberrant myeloid cell subset trafficking and further defines the molecular mechanisms underlying this regulation.",,"['Ghosh, Mallika', 'Gerber, Claire', 'Rahman, M Mamunur', 'Vernier, Kaitlyn M', 'Pereira, Flavia E', 'Subramani, Jaganathan', 'Caromile, Leslie A', 'Shapiro, Linda H']",,,,
,PMC,"Characterization of a Monoclonal Antibody to a Novel Glycan-Dependent Epitope in the V1/V2 Domain of the HIV-1 Envelope Protein, gp120",http://dx.doi.org/10.1016/j.molimm.2014.06.025,PMC4157072,,,"Recent studies have described several broadly neutralizing monoclonal antibodies (bN-mAbs) that recognize glycan-dependent epitopes (GDEs) in the HIV-1 envelope protein, gp120. These were recovered from HIV-1 infected subjects, and several (e.g., PG9, PG16, CH01, CH03) target glycans in the first and second variable (V1/V2) domain of gp120. The V1/V2 domain is thought to play an important role in conformational masking, and antibodies to the V1/V2 domain were recently identified as the only immune response that correlated with protection in the RV144 HIV-1 vaccine trial. While the importance of antibodies to polymeric glycans is well established for vaccines targeting bacterial diseases, the importance of antibodies to glycans in vaccines targeting HIV has only recently been recognized. Antibodies to GDEs may be particularly significant in HIV vaccines based on gp120, where 50% of the molecular mass of the envelope protein is contributed by N-linked carbohydrate. However, few studies have reported antibodies to GDEs in humans or animals immunized with candidate HIV-1 vaccines. In this report, we describe the isolation of a mouse mAb, 4B6, after immunization with the extracellular domain of the HIV-1 envelope protein, gp140. Epitope mapping using glycopeptide fragments and in vitro mutagenesis showed that binding of this antibody depends on N-linked glycosylation at asparagine N130 (HXB2 numbering) in the gp120 V1/V2 domain. Our results demonstrate that, in addition to natural HIV-1 infection, immunization with recombinant proteins can elicit antibodies to the GDEs in the V1/V2 domain of gp120. Although little is known regarding conditions that favor antibody responses to GDEs, our studies demonstrate that these antibodies can arise from a short-term immunization regimen. Our results suggest that antibodies to GDEs are more common than previously suspected, and that further analysis of antibody responses to the HIV-1 envelope protein will lead to the discovery of additional antibodies to GDEs.",,"['Doran, Rachel C.', 'Morales, Javier F.', 'To, Briana', 'Morin, Trevor J.', 'Theolis, Richard', 'O’Rourke, Sara M.', 'Yu, Bin', 'Mesa, Kathryn A.', 'Berman, Phillip W.']",,,,
,PMC,Coronavirus-induced demyelination of neural pathways triggers neurogenic bladder overactivity in a mouse model of multiple sclerosis,http://dx.doi.org/10.1152/ajprenal.00151.2014,PMC4154110,,,"In the present study, we aimed to determine whether mice with coronavirus-induced encephalomyelitis (CIE) develop neurogenic bladder dysfunction that is comparable with the neurogenic detrusor overactivity observed in patients with multiple sclerosis. Adult mice (C57BL/6J, 8 wk of age, n = 146) were inoculated with a neurotropic strain of mouse hepatitis virus (A59 strain) and followed for 4 wk. Inoculation with the virus caused a significant neural deficit in mice with an average clinical symptom score of 2.6 ± 0.5 at 2 wk. These changes were accompanied by 25 ± 5% weight loss at 1 and 2 wk postinoculation (P ≤ 0.001 vs. baseline) followed by a recovery phase. Histological analysis of spinal cord sections revealed multifocal sites of demyelinated lesions. Assessment of micturition patterns by filter paper assay determined an increase in the number of small and large urine spots in CIE mice starting from the second week after inoculation. Cystometric recordings in unrestrained awake animals confirmed neurogenic bladder overactivity at 4 wk postinoculation. One week after inoculation with the A59 strain of mouse hepatitis virus, mice became increasingly sensitive to von Frey filament testing with responses enhanced by 45% (n = 8, P ≤ 0.05 vs. baseline at 4 g); however, this initial increase in sensitivity was followed by gradual and significant diminution of abdominal sensitivity to mechanical stimulation by 4 wk postinoculation. Our results provide direct evidence showing that coronavirus-induced demyelination of the central nervous system causes the development of a neurogenic bladder that is comparable with neurogenic detrusor overactivity observed in patients with multiple sclerosis.",,"['McMillan, Matthew T.', 'Pan, Xiao-Qing', 'Smith, Ariana L.', 'Newman, Diane K.', 'Weiss, Susan R.', 'Ruggieri, Michael R.', 'Malykhina, Anna P.']",,,,
,PMC,10 health stories that mattered: May 19–23,http://dx.doi.org/10.1503/cmaj.109-4816,PMC4081222,,,,,"Collier, Roger",,,,
,PMC,Call for infection control to stem MERS,http://dx.doi.org/10.1503/cmaj.109-4806,PMC4081218,,,,,"Brown, Carolyn",,,,
,PMC,10 health stories that mattered May 12–16,http://dx.doi.org/10.1503/cmaj.109-4810,PMC4081214,,,,,"Collier, Roger",,,,
,PMC,Dengue Virus in Bats from Southeastern Mexico,http://dx.doi.org/10.4269/ajtmh.13-0524,PMC4080551,,,"To identify the relationship between landscape use and dengue virus (DENV) occurrence in bats, we investigated the presence of DENV from anthropogenically changed and unaltered landscapes in two Biosphere Reserves: Calakmul (Campeche) and Montes Azules (Chiapas) in southern Mexico. Spleen samples of 146 bats, belonging to 16 species, were tested for four DENV serotypes with standard reverse transcriptase polymerase chain reaction (RT-PCR) protocols. Six bats (4.1%) tested positive for DENV-2: four bats in Calakmul (two Glossophaga soricina, one Artibeus jamaicensis, and one A. lituratus) and two bats in Montes Azules (both A. lituratus). No effect of anthropogenic disturbance on the occurrence of DENV was detected; however, all three RT-PCR–positive bat species are considered abundant species in the Neotropics and well-adapted to disturbed habitats. To our knowledge, this study is the first study conducted in southeastern Mexico to identify DENV-2 in bats by a widely accepted RT-PCR protocol. The role that bats play on DENV's ecology remains undetermined.",,"['Sotomayor-Bonilla, Jesús', 'Chaves, Andrea', 'Rico-Chávez, Oscar', 'Rostal, Melinda K.', 'Ojeda-Flores, Rafael', 'Salas-Rojas, Mónica', 'Aguilar-Setien, Álvaro', 'Ibáñez-Bernal, Sergio', 'Barbachano-Guerrero, Arturo', 'Gutiérrez-Espeleta, Gustavo', 'Aguilar-Faisal, J. Leopoldo', 'Aguirre, A. Alonso', 'Daszak, Peter', 'Suzán, Gerardo']",,,,
,PMC,Antiviral Drugs Specific for Coronaviruses in Preclinical Development,http://dx.doi.org/10.1016/j.coviro.2014.06.002,PMC4195804,,,"Coronaviruses are positive stranded RNA viruses that cause respiratory, enteric and central nervous system diseases in many species, including humans. Until recently, the relatively low burden of disease in humans caused by few of these viruses impeded the development of coronavirus specific therapeutics. However, the emergence of severe acute respiratory syndrome coronavirus (SARS-CoV), and more recently, Middle East respiratory syndrome coronavirus (MERS-CoV), has impelled the development of such drugs. This review focuses on some newly identified SARS-CoV inhibitors, with known mechanisms of action and their potential to inhibit the novel MERS-CoV. The clinical development of optimized versions of such compounds could be beneficial for the treatment and control of SARS-CoV, the current MERS-CoV and other future SARS-like epidemics.",,"['Adedeji, Adeyemi O.', 'Sarafianos, Stefan G.']",,,,
,PMC,Mainstreaming Modeling and Simulation to Accelerate Public Health Innovation,http://dx.doi.org/10.2105/AJPH.2014.301873,PMC4056212,,,"Dynamic modeling and simulation are systems science tools that examine behaviors and outcomes resulting from interactions among multiple system components over time. Although there are excellent examples of their application, they have not been adopted as mainstream tools in population health planning and policymaking. Impediments to their use include the legacy and ease of use of statistical approaches that produce estimates with confidence intervals, the difficulty of multidisciplinary collaboration for modeling and simulation, systems scientists’ inability to communicate effectively the added value of the tools, and low funding for population health systems science. Proposed remedies include aggregation of diverse data sets, systems science training for public health and other health professionals, changing research incentives toward collaboration, and increased funding for population health systems science projects.",,"['Maglio, Paul P.', 'Sepulveda, Martin-J.', 'Mabry, Patricia L.']",,,,
,PMC,Inhibition of Aminoglycoside 6′-N-Acetyltransferase Type Ib by Zinc: Reversal of Amikacin Resistance in Acinetobacter baumannii and Escherichia coli by a Zinc Ionophore,http://dx.doi.org/10.1128/AAC.00129-14,PMC4068593,,,In vitro activity of the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib] was inhibited by ZnCl(2) with a 50% inhibitory concentration (IC(50)) of 15 μM. Growth of Acinetobacter baumannii or Escherichia coli harboring aac(6′)-Ib in cultures containing 8 μg/ml amikacin was significantly inhibited by the addition of 2 μM Zn(2+) in complex with the ionophore pyrithione (ZnPT).,,"['Lin, David L.', 'Tran, Tung', 'Alam, Jamal Y.', 'Herron, Steven R.', 'Ramirez, Maria Soledad', 'Tolmasky, Marcelo E.']",,,,
,PMC,Comparison of Five Bacteriophages as Models for Viral Aerosol Studies,http://dx.doi.org/10.1128/AEM.00767-14,PMC4068686,,,"Bacteriophages are perceived to be good models for the study of airborne viruses because they are safe to use, some of them display structural features similar to those of human and animal viruses, and they are relatively easy to produce in large quantities. Yet, only a few studies have investigated them as models. It has previously been demonstrated that aerosolization, environmental conditions, and sampling conditions affect viral infectivity, but viral infectivity is virus dependent. Thus, several virus models are likely needed to study their general behavior in aerosols. The aim of this study was to compare the effects of aerosolization and sampling on the infectivity of five tail-less bacteriophages and two pathogenic viruses: MS2 (a single-stranded RNA [ssRNA] phage of the Leviviridae family), Φ6 (a segmented double-stranded RNA [dsRNA] phage of the Cystoviridae family), ΦX174 (a single-stranded DNA [ssDNA] phage of the Microviridae family), PM2 (a double-stranded DNA [dsDNA] phage of the Corticoviridae family), PR772 (a dsDNA phage of the Tectiviridae family), human influenza A virus H1N1 (an ssRNA virus of the Orthomyxoviridae family), and the poultry virus Newcastle disease virus (NDV; an ssRNA virus of the Paramyxoviridae family). Three nebulizers and two nebulization salt buffers (with or without organic fluid) were tested, as were two aerosol sampling devices, a liquid cyclone (SKC BioSampler) and a dry cyclone (National Institute for Occupational Safety and Health two-stage cyclone bioaerosol sampler). The presence of viruses in collected air samples was detected by culture and quantitative PCR (qPCR). Our results showed that these selected five phages behave differently when aerosolized and sampled. RNA phage MS2 and ssDNA phage ΦX174 were the most resistant to aerosolization and sampling. The presence of organic fluid in the nebulization buffer protected phages PR772 and Φ6 throughout the aerosolization and sampling with dry cyclones. In this experimental setup, the behavior of the influenza virus resembled that of phages PR772 and Φ6, while the behavior of NDV was closer to that of phages MS2 and ΦX174. These results provide critical information for the selection of appropriate phage models to mimic the behavior of specific human and animal viruses in aerosols.",,"['Turgeon, Nathalie', 'Toulouse, Marie-Josée', 'Martel, Bruno', 'Moineau, Sylvain', 'Duchaine, Caroline']",,,,
,PMC,Classical Renin-Angiotensin System in Kidney Physiology,http://dx.doi.org/10.1002/cphy.c130040,PMC4137912,,,"The renin-angiotensin system has powerful effects in control of the blood pressure and sodium homeostasis. These actions are coordinated through integrated actions in the kidney, cardio-vascular system and the central nervous system. Along with its impact on blood pressure, the renin-angiotensin system also influences a range of processes from inflammation and immune responses to longevity. Here, we review the actions of the “classical” renin-angiotensin system, whereby the substrate protein angiotensinogen is processed in a two-step reaction by renin and angiotensin converting enzyme, resulting in the sequential generation of angiotensin I and angiotensin II, the major biologically active renin-angiotensin system peptide, which exerts its actions via type 1 and type 2 angiotensin receptors. In recent years, several new enzymes, peptides, and receptors related to the renin-angiotensin system have been identified, manifesting a complexity that was previously unappreciated. While the functions of these alternative pathways will be reviewed elsewhere in this journal, our focus here is on the physiological role of components of the “classical” renin-angiotensin system, with an emphasis on new developments and modern concepts.",,"['Sparks, Matthew A.', 'Crowley, Steven D.', 'Gurley, Susan B.', 'Mirotsou, Maria', 'Coffman, Thomas M.']",,,,
,PMC,The Ongoing Challenge of Evaluating Rescue Therapies in ARDS,http://dx.doi.org/10.1097/CCM.0000000000000390,PMC4118925,,,,,"['Keriwala, Raj D.', 'Rice, Todd W.']",,,,
,PMC,Long-term Survival in Patients with Severe Acute Respiratory Distress Syndrome and Rescue Therapies for Refractory Hypoxemia,http://dx.doi.org/10.1097/CCM.0000000000000322,PMC4061153,,,"OBJECTIVE: To describe long-term survival in patients with severe acute respiratory distress syndrome (ARDS) and assess differences in patient characteristics and outcomes among those who receive rescue therapies (prone position ventilation, inhaled nitric oxide, or inhaled epoprostenol) versus conventional treatment. DESIGN AND SETTING: Cohort study of patients with severe hypoxemia at a University-affiliated Level 1 trauma center. PATIENTS: Patients diagnosed with severe ARDS within 72 hours of ICU admission between 1/1/2008 and 12/31/2011. METHODS: Data were abstracted from the medical record and included demographic and clinical variables, hospital and ICU length of stay, discharge disposition, and hospital costs. Patient-level data were linked to the Washington State Death Registry. Kaplan-Meier methods and Cox's proportional hazards models were used to estimate survival and hazard ratios. MAIN RESULTS: 428 patients meeting study inclusion criteria were identified; 62 (14%) were initiated on a rescue therapy. PaO(2)/FIO(2) ratios were comparable at admission between patients treated with a rescue therapy and those treated conventionally, but were substantially lower by 72 hours in those who received rescue therapies (54 ± 17 versus 69 ± 17 mmHg; p<.01). For the entire cohort, estimated survival probability at three years was 55% (95% CI: 51%, 61%). Among 280 hospital survivors (65%), three-year survival was 85% (95% CI: 80%, 89%). The relative hazard of in-hospital mortality was 68% higher among patients who received rescue therapy compared to patients treated conventionally (95% CI: 8%, 162%; p=0.02). For long-term survival, the hazard ratio of death following ICU admission was 1.56 (95% CI: 1.02, 2.37; p=0.04), comparing rescue versus conventional treatment. CONCLUSIONS: Despite high hospital mortality, severe ARDS patients surviving to hospital discharge have relatively good long-term survival. Worsening hypoxemia was associated with initiation of rescue therapy. Patients on rescue therapy had higher in-hospital mortality; however, survivors to hospital discharge had long-term survival that was comparable to other ARDS survivors.",,"['Khandelwal, Nita', 'Hough, Catherine L.', 'Bansal, Aasthaa', 'Veenstra, David L.', 'Treggiari, Miriam M.']",,,,
,PMC,Axonal Pathology and Demyelination in Viral Models of Multiple Sclerosis,,PMC4371782,,,"Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease of the central nervous system (CNS). Monozygotic twin studies suggest that while there is a genetic contribution, genetics alone cannot be the sole determining factor in the development of MS. As the rates of MS are increasing, particularly among women, environmental factors such as viral infections are coming to the foreground as potential agents in triggering disease in genetically susceptible individuals. This review highlights pathological aspects related to two pre-clinical viral models for MS; data are consistent between these two models as experimental infection of susceptible mice can induce axonal degeneration associated with demyelination. These data are consistent with observations in MS that axonal damage or Wallerian degeneration is occurring within the CNS contributing to the disability and disease severity. Such early damage, where axonal damage is primary to secondary demyelination, could set the stage for more extensive immune mediated demyelination arising later.",,"['Libbey, Jane E.', 'Lane, Thomas E.', 'Fujinami, Robert S.']",,,,
,PMC,The essential roles of chemistry in high-throughput screening triage,http://dx.doi.org/10.4155/fmc.14.60,PMC4465542,,,"It is increasingly clear that academic high-throughput screening (HTS) and virtual HTS triage suffers from a lack of scientists trained in the art and science of early drug discovery chemistry. Many recent publications report the discovery of compounds by screening that are most likely artifacts or promiscuous bioactive compounds, and these results are not placed into the context of previous studies. For HTS to be most successful, it is our contention that there must exist an early partnership between biologists and medicinal chemists. Their combined skill sets are necessary to design robust assays and efficient workflows that will weed out assay artifacts, false positives, promiscuous bioactive compounds and intractable screening hits, efforts that ultimately give projects a better chance at identifying truly useful chemical matter. Expertise in medicinal chemistry, cheminformatics and purification sciences (analytical chemistry) can enhance the post-HTS triage process by quickly removing these problematic chemotypes from consideration, while simultaneously prioritizing the more promising chemical matter for follow-up testing. It is only when biologists and chemists collaborate effectively that HTS can manifest its full promise.",,"['Dahlin, Jayme L', 'Walters, Michael A']",,,,
,PMC,A cloud-compatible bioinformatics pipeline for ultrarapid pathogen identification from next-generation sequencing of clinical samples,http://dx.doi.org/10.1101/gr.171934.113,PMC4079973,,,"Unbiased next-generation sequencing (NGS) approaches enable comprehensive pathogen detection in the clinical microbiology laboratory and have numerous applications for public health surveillance, outbreak investigation, and the diagnosis of infectious diseases. However, practical deployment of the technology is hindered by the bioinformatics challenge of analyzing results accurately and in a clinically relevant timeframe. Here we describe SURPI (“sequence-based ultrarapid pathogen identification”), a computational pipeline for pathogen identification from complex metagenomic NGS data generated from clinical samples, and demonstrate use of the pipeline in the analysis of 237 clinical samples comprising more than 1.1 billion sequences. Deployable on both cloud-based and standalone servers, SURPI leverages two state-of-the-art aligners for accelerated analyses, SNAP and RAPSearch, which are as accurate as existing bioinformatics tools but orders of magnitude faster in performance. In fast mode, SURPI detects viruses and bacteria by scanning data sets of 7–500 million reads in 11 min to 5 h, while in comprehensive mode, all known microorganisms are identified, followed by de novo assembly and protein homology searches for divergent viruses in 50 min to 16 h. SURPI has also directly contributed to real-time microbial diagnosis in acutely ill patients, underscoring its potential key role in the development of unbiased NGS-based clinical assays in infectious diseases that demand rapid turnaround times.",,"['Naccache, Samia N.', 'Federman, Scot', 'Veeraraghavan, Narayanan', 'Zaharia, Matei', 'Lee, Deanna', 'Samayoa, Erik', 'Bouquet, Jerome', 'Greninger, Alexander L.', 'Luk, Ka-Cheung', 'Enge, Barryett', 'Wadford, Debra A.', 'Messenger, Sharon L.', 'Genrich, Gillian L.', 'Pellegrino, Kristen', 'Grard, Gilda', 'Leroy, Eric', 'Schneider, Bradley S.', 'Fair, Joseph N.', 'Martínez, Miguel A.', 'Isa, Pavel', 'Crump, John A.', 'DeRisi, Joseph L.', 'Sittler, Taylor', 'Hackett, John', 'Miller, Steve', 'Chiu, Charles Y.']",,,,
,PMC,VCAM-1/α4β1 Integrin Interaction Is Crucial for Prompt Recruitment of Immune T Cells into the Brain during the Early Stage of Reactivation of Chronic Infection with Toxoplasma gondii To Prevent Toxoplasmic Encephalitis,http://dx.doi.org/10.1128/IAI.01494-13,PMC4097612,,,"Reactivation of chronic infection with Toxoplasma gondii can cause life-threatening toxoplasmic encephalitis in immunocompromised individuals. We examined the role of VCAM-1/α4β1 integrin interaction in T cell recruitment to prevent reactivation of the infection in the brain. SCID mice were infected and treated with sulfadiazine to establish a chronic infection. VCAM-1 and ICAM-1 were the endothelial adhesion molecules detected on cerebral vessels of the infected SCID and wild-type animals. Immune T cells from infected wild-type mice were treated with anti-α4 integrin or control antibodies and transferred into infected SCID or nude mice, and the animals received the same antibody every other day. Three days later, sulfadiazine was discontinued to initiate reactivation of infection. Expression of mRNAs for CD3δ, CD4, CD8β, gamma interferon (IFN-γ), and inducible nitric oxide synthase (NOS2) (an effector molecule to inhibit T. gondii growth) and the numbers of CD4(+) and CD8(+) T cells in the brain were significantly less in mice treated with anti-α4 integrin antibody than in those treated with control antibody at 3 days after sulfadiazine discontinuation. At 6 days after sulfadiazine discontinuation, cerebral tachyzoite-specific SAG1 mRNA levels and numbers of inflammatory foci associated with tachyzoites were markedly greater in anti-α4 integrin antibody-treated than in control antibody-treated animals, even though IFN-γ and NOS2 mRNA levels were higher in the former than in the latter. These results indicate that VCAM-1/α4β1 integrin interaction is crucial for prompt recruitment of immune T cells and induction of IFN-γ-mediated protective immune responses during the early stage of reactivation of chronic T. gondii infection to control tachyzoite growth.",,"['Sa, Qila', 'Ochiai, Eri', 'Sengoku, Tomoko', 'Wilson, Melinda E.', 'Brogli, Morgan', 'Crutcher, Stephen', 'Michie, Sara A.', 'Xu, Baohui', 'Payne, Laura', 'Wang, Xisheng', 'Suzuki, Yasuhiro']",,,,
,PMC,Procalcitonin versus C-reactive protein: Usefulness as biomarker of sepsis in ICU patient,http://dx.doi.org/10.4103/2229-5151.141356,PMC4200544,25337480,CC BY-NC-SA,"BACKGROUND: Early diagnosis and appropriate therapy of sepsis is a daily challenge in intensive care units (ICUs) despite the advances in critical care medicine. Procalcitonin (PCT); an innovative laboratory marker, has been recently proven valuable worldwide in this regard. OBJECTIVES: This study was undertaken to evaluate the utility of PCT in a resource constrained country like ours when compared to the traditional inflammatory markers like C - reactive protein (CRP) to introduce PCT as a routine biochemical tool in regional hospitals. MATERIALS AND METHODS: PCT and CRP were simultaneously measured and compared in 73 medico-surgical ICU patients according to the American College of Chest Physicians (ACCP) criteria based study groups. RESULTS: The clinical presentation of 75% cases revealed a range of systemic inflammatory responses (SIRS). The diagnostic accuracy of PCT was higher (75%) with greater specificity (72%), sensitivity (76%), positive and negative predictive values (89% and 50%), positive likelihood ratio (2.75) as well as the smaller negative likelihood ratio (0.33). Both serum PCT and CRP values in cases with sepsis, severe sepsis and septic shock were significantly higher from that of the cases with SIRS and no SIRS (P < 0.01). CONCLUSION: PCT is found to be superior to CRP in terms of accuracy in identification and to assess the severity of sepsis even though both markers cannot be used in differentiating infectious from noninfectious clinical syndrome.",2014 Jul-Sep,"['Nargis, Waheeda', 'Ibrahim, Md', 'Ahamed, Borhan Uddin']",Int J Crit Illn Inj Sci,,,
,PMC,Bioterrorism: a Laboratory Who Does It?,http://dx.doi.org/10.1128/JCM.00359-14,PMC4097698,,,"In October 2001, the first disseminated biological warfare attack was perpetrated on American soil. Initially, a few clinical microbiology laboratories were testing specimens from acutely ill patients and also being asked to test nasal swabs from the potentially exposed. Soon after, a significant number of clinical microbiology and public health laboratories received similar requests to test the worried well or evaluate potentially contaminated mail or environmental materials, sometimes from their own break rooms. The role of the clinical and public health microbiology laboratory in response to a select agent event or act of bioterrorism is reviewed.",,"['Craft, David W.', 'Lee, Philip A.', 'Rowlinson, Marie-Claire']",,,,
,PMC,New Approach for Phylogenetic Tree Recovery Based on Genome-Scale Metabolic Networks,http://dx.doi.org/10.1089/cmb.2013.0150,PMC4082356,,,"A wide range of applications and research has been done with genome-scale metabolic models. In this work, we describe an innovative methodology for comparing metabolic networks constructed from genome-scale metabolic models and how to apply this comparison in order to infer evolutionary distances between different organisms. Our methodology allows a quantification of the metabolic differences between different species from a broad range of families and even kingdoms. This quantification is then applied in order to reconstruct phylogenetic trees for sets of various organisms.",,"['Gamermann, Daniel', 'Montagud, Arnaud', 'Conejero, J. Alberto', 'Urchueguía, Javier F.', 'de Córdoba, Pedro Fernández']",,,,
,PMC,Arrival time pattern and waiting time distribution of patients in the emergency outpatient department of a tertiary level health care institution of North India,http://dx.doi.org/10.4103/0974-2700.136855,PMC4126114,25114424,CC BY-NC-SA,"BACKGROUND: Emergency Department (ED) of tertiary health care institute in India is mostly overcrowded, over utilized and inappropriately staffed. The challenges of overcrowded EDs and ill-managed patient flow and admission processes result in excessively long waits for patients. AIM: The objective of the present study was to analyze the patient flow system by assessing the arrival and waiting time distribution of patients in an Emergency out Patient Department (EOPD). MATERIALS AND METHODS: This short cross-sectional descriptive study was conducted in the EOPD of a Tertiary level health care Institution in North India in the month of May, 2011. The data was obtained from 591 patients, who were present in the EOPD during the month of May, 2011. The waiting time, inter arrival time between two consecutive patients were calculated in addition to the daily census data (discharge rate, admission rate and transfer out rates etc.) of the emergency. RESULTS: Arrival time pattern of patients in the EOPD was highly stochastic with the peak arrival hours to be 9.00-12.00 h in which around 26.3% patients arrived in the EOPD. The primary waiting areas of patients included patients under observation (29.6%); waiting for routine diagnostic tests (16.4%) and waiting for discharge (14.6%). Around 71% patients were waiting due to reasons within emergency complex. CONCLUSION: The patient flow of the ED could only be addressed by multifaceted, multidisciplinary and hospital wide approach.",2014 Jul-Sep,"['Tiwari, Yogesh', 'Goel, Sonu', 'Singh, Amarjeet']",J Emerg Trauma Shock,,,
,PMC,Specificities of Human CD4(+) T Cell Responses to an Inactivated Flavivirus Vaccine and Infection: Correlation with Structure and Epitope Prediction,http://dx.doi.org/10.1128/JVI.00196-14,PMC4097808,,,"Tick-borne encephalitis (TBE) virus is endemic in large parts of Europe and Central and Eastern Asia and causes more than 10,000 annual cases of neurological disease in humans. It is closely related to the mosquito-borne yellow fever, dengue, Japanese encephalitis, and West Nile viruses, and vaccination with an inactivated whole-virus vaccine can effectively prevent clinical disease. Neutralizing antibodies are directed to the viral envelope protein (E) and an accepted correlate of immunity. However, data on the specificities of CD4(+) T cells that recognize epitopes in the viral structural proteins and thus can provide direct help to the B cells producing E-specific antibodies are lacking. We therefore conducted a study on the CD4(+) T cell response against the virion proteins in vaccinated people in comparison to TBE patients. The data obtained with overlapping peptides in interleukin-2 (IL-2) enzyme-linked immunosorbent spot (ELISpot) assays were analyzed in relation to the three-dimensional structures of the capsid (C) and E proteins as well as to epitope predictions based on major histocompatibility complex (MHC) class II peptide affinities. In the C protein, peptides corresponding to two out of four alpha helices dominated the response in both vaccinees and patients, whereas in the E protein concordance of immunodominance was restricted to peptides of a single domain (domain III). Epitope predictions were much better for C than for E and were especially erroneous for the transmembrane regions. Our data provide evidence for a strong impact of protein structural features that influence peptide processing, contributing to the discrepancies observed between experimentally determined and computer-predicted CD4(+) T cell epitopes. IMPORTANCE Tick-borne encephalitis virus is endemic in large parts of Europe and Asia and causes more than 10,000 annual cases of neurological disease in humans. It is closely related to yellow fever, dengue, Japanese encephalitis, and West Nile viruses, and vaccination with an inactivated vaccine can effectively prevent disease. Both vaccination and natural infection induce the formation of antibodies to a viral surface protein that neutralize the infectivity of the virus and mediate protection. B lymphocytes synthesizing these antibodies require help from other lymphocytes (helper T cells) which recognize small peptides derived from proteins contained in the viral particle. Which of these peptides dominate immune responses to vaccination and infection, however, was unknown. In our study we demonstrate which parts of the proteins contribute most strongly to the helper T cell response, highlight specific weaknesses of currently available approaches for their prediction, and demonstrate similarities and differences between vaccination and infection.",,"['Schwaiger, Julia', 'Aberle, Judith H.', 'Stiasny, Karin', 'Knapp, Bernhard', 'Schreiner, Wolfgang', 'Fae, Ingrid', 'Fischer, Gottfried', 'Scheinost, Ondrej', 'Chmelik, Vaclav', 'Heinz, Franz X.']",,,,
,PMC,African Green Monkeys Recapitulate the Clinical Experience with Replication of Live Attenuated Pandemic Influenza Virus Vaccine Candidates,http://dx.doi.org/10.1128/JVI.00425-14,PMC4097805,,,"Live attenuated cold-adapted (ca) H5N1, H7N3, H6N1, and H9N2 influenza vaccine viruses replicated in the respiratory tract of mice and ferrets, and 2 doses of vaccines were immunogenic and protected these animals from challenge infection with homologous and heterologous wild-type (wt) viruses of the corresponding subtypes. However, when these vaccine candidates were evaluated in phase I clinical trials, there were inconsistencies between the observations in animal models and in humans. The vaccine viruses did not replicate well and immune responses were variable in humans, even though the study subjects were seronegative with respect to the vaccine viruses before vaccination. Therefore, we sought a model that would better reflect the findings in humans and evaluated African green monkeys (AGMs) as a nonhuman primate model. The distribution of sialic acid (SA) receptors in the respiratory tract of AGMs was similar to that in humans. We evaluated the replication of wt and ca viruses of avian influenza (AI) virus subtypes H5N1, H6N1, H7N3, and H9N2 in the respiratory tract of AGMs. All of the wt viruses replicated efficiently, while replication of the ca vaccine viruses was restricted to the upper respiratory tract. Interestingly, the patterns and sites of virus replication differed among the different subtypes. We also evaluated the immunogenicity and protective efficacy of H5N1, H6N1, H7N3, and H9N2 ca vaccines. Protection from wt virus challenge correlated well with the level of serum neutralizing antibodies. Immune responses were slightly better when vaccine was delivered by both intranasal and intratracheal delivery than when it was delivered intranasally by sprayer. We conclude that live attenuated pandemic influenza virus vaccines replicate similarly in AGMs and human subjects and that AGMs may be a useful model to evaluate the replication of ca vaccine candidates. IMPORTANCE Ferrets and mice are commonly used for preclinical evaluation of influenza vaccines. However, we observed significant inconsistencies between observations in humans and in these animal models. We used African green monkeys (AGMs) as a nonhuman primate (NHP) model for a comprehensive and comparative evaluation of pairs of wild-type and pandemic live attenuated influenza virus vaccines (pLAIV) representing four subtypes of avian influenza viruses and found that pLAIVs replicate similarly in AGMs and humans and that AGMs can be useful for evaluation of the protective efficacy of pLAIV.",,"['Matsuoka, Yumiko', 'Suguitan, Amorsolo', 'Orandle, Marlene', 'Paskel, Myeisha', 'Boonnak, Kobporn', 'Gardner, Donald J.', 'Feldmann, Friederike', 'Feldmann, Heinz', 'Marino, Michael', 'Jin, Hong', 'Kemble, George', 'Subbarao, Kanta']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.01434-14,PMC4097790,,,,,,,,,
,PMC,Careers in Virology: Public Health Opportunities for Early-Career Basic Scientists,http://dx.doi.org/10.1128/JVI.00911-14,PMC4097789,,,"Undergraduate, graduate, and postdoctoral scientists trained as virologists can play critical roles in public health, such as in health science policy, epidemiology, and national defense. Despite a need for basic science backgrounds within these fields, finding entry-level careers can be challenging. Volunteer opportunities are a great way for scientists to experience public health careers while still in school, and this article describes volunteering with the Medical Reserve Corps and outlines unique postgraduate opportunities for early-career virologists.",,"Kilianski, Andy",,,,
,PMC,Proteolytic Activation of the Porcine Epidemic Diarrhea Coronavirus Spike Fusion Protein by Trypsin in Cell Culture,http://dx.doi.org/10.1128/JVI.00297-14,PMC4097775,,,"Isolation of porcine epidemic diarrhea coronavirus (PEDV) from clinical material in cell culture requires supplementation of trypsin. This may relate to the confinement of PEDV natural infection to the protease-rich small intestine of pigs. Our study focused on the role of protease activity on infection by investigating the spike protein of a PEDV isolate (wtPEDV) using a reverse genetics system based on the trypsin-independent cell culture-adapted strain DR13 (caPEDV). We demonstrate that trypsin acts on the wtPEDV spike protein after receptor binding. We mapped the genetic determinant for trypsin-dependent cell entry to the N-terminal region of the fusion subunit of this class I fusion protein, revealing a conserved arginine just upstream of the putative fusion peptide as the potential cleavage site. Whereas coronaviruses are typically processed by endogenous proteases of the producer or target cell, PEDV S protein activation strictly required supplementation of a protease, enabling us to study mechanistic details of proteolytic processing. IMPORTANCE Recurring PEDV epidemics constitute a serious animal health threat and an economic burden, particularly in Asia but, as of recently, also on the North-American subcontinent. Understanding the biology of PEDV is critical for combatting the infection. Here, we provide new insight into the protease-dependent cell entry of PEDV.",,"['Wicht, Oliver', 'Li, Wentao', 'Willems, Lione', 'Meuleman, Tom J.', 'Wubbolts, Richard W.', 'van Kuppeveld, Frank J. M.', 'Rottier, Peter J. M.', 'Bosch, Berend Jan']",,,,
,PMC,Exceptionally Potent Neutralization of Middle East Respiratory Syndrome Coronavirus by Human Monoclonal Antibodies,http://dx.doi.org/10.1128/JVI.00912-14,PMC4097770,,,"The recently discovered Middle East respiratory syndrome coronavirus (MERS-CoV) continues to infect humans, with high mortality. Specific, highly effective therapeutics and vaccines against the MERS-CoV are urgently needed to save human lives and address the pandemic concerns. We identified three human monoclonal antibodies (MAbs), m336, m337, and m338, targeting the receptor (CD26/DPP4) binding domain (RBD) of the MERS-CoV spike glycoprotein from a very large naïve-antibody library (containing ∼10(11) antibodies). They bound with high affinity: equilibrium dissociation constants for the three MAbs were equal to 4.2, 9.3, and 15 nM, respectively, as measured by Biacore for Fabs binding to RBD. The avidity for IgG1 m336, m337, and m338 was even higher: 99, 820, and 560 pM, respectively. The antibodies bound to overlapping epitopes that overlap the receptor binding site on the RBD as suggested by competition experiments and further supported by site-directed mutagenesis of the RBD and a docking model of the m336-RBD complex. The highest-affinity MAb, m336, neutralized both pseudotyped and live MERS-CoV with exceptional potency, 50% neutralization at 0.005 and 0.07 μg/ml, respectively, likely by competing with DPP4 for binding to the S glycoprotein. The exceptionally high neutralization activity of these antibodies and especially m336 suggests that they have great potential for prophylaxis and therapy of MERS-CoV infection in humans and as a tool for development of vaccine immunogens. The rapid identification (within several weeks) of potent MAbs suggests a possibility to use the new large antibody library and related methodology for a quick response to the public threat resulting from emerging coronaviruses. IMPORTANCE A novel human coronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV), was found to infect humans with a high mortality rate in 2012, just 1 decade after the appearance of the first highly pathogenic coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV). There are no effective therapeutics available. It is highly desirable to find an approach for rapidly developing potent therapeutics against MERS-CoV, which not only can be implemented for MERS treatment but also can help to develop a platform strategy to combat future emerging coronaviruses. We report here the identification of human monoclonal antibodies (MAbs) from a large nonimmune antibody library that target MERS-CoV. One of the antibodies, m336, neutralized the virus with exceptional potency. It therefore may have great potential as a candidate therapeutic and as a reagent to facilitate the development of vaccines against MERS-CoV.",,"['Ying, Tianlei', 'Du, Lanying', 'Ju, Tina W.', 'Prabakaran, Ponraj', 'Lau, Candy C. Y.', 'Lu, Lu', 'Liu, Qi', 'Wang, Lili', 'Feng, Yang', 'Wang, Yanping', 'Zheng, Bo-Jian', 'Yuen, Kwok-Yung', 'Jiang, Shibo', 'Dimitrov, Dimiter S.']",,,,
,PMC,Analysis of Lujo Virus Cell Entry using Pseudotype Vesicular Stomatitis Virus,http://dx.doi.org/10.1128/JVI.00512-14,PMC4054455,,,"Several arenaviruses are known to cause viral hemorrhagic fever (VHF) in sub-Saharan Africa and South America, where VHF is a major public health and medical concern. The biosafety level 4 categorization of these arenaviruses restricts their use and has impeded biological studies, including therapeutic drug and/or vaccine development. Due to difficulties associated with handling live viruses, pseudotype viruses, which transiently bear arenavirus envelope proteins based on vesicular stomatitis virus (VSV) or retrovirus, have been developed as surrogate virus systems. Here, we report the development of a pseudotype VSV bearing each envelope protein of various species of arenaviruses (AREpv), including the newly identified Lujo virus (LUJV) and Chapare virus. Pseudotype arenaviruses generated in 293T cells exhibited high infectivity in various mammalian cell lines. The infections by New World and Old World AREpv were dependent on their receptors (human transferrin receptor 1 [hTfR1] and α-dystroglycan [αDG], respectively). However, infection by pseudotype VSV bearing the LUJV envelope protein (LUJpv) occurred independently of hTfR1 and αDG, indicating that LUJpv utilizes an unidentified receptor. The pH-dependent endocytosis of AREpv was confirmed by the use of lysosomotropic agents. The fusion of cells expressing these envelope proteins, except for those expressing the LUJV envelope protein, was induced by transient treatment at low pH values. LUJpv infectivity was inhibited by U18666A, a cholesterol transport inhibitor. Furthermore, the infectivity of LUJpv was significantly decreased in the Niemann-Pick C1 (NPC1)-deficient cell line, suggesting the necessity for NPC1 activity for efficient LUJpv infection. IMPORTANCE LUJV is a newly identified arenavirus associated with a VHF outbreak in southern Africa. Although cell entry for many arenaviruses has been studied, cell entry for LUJV has not been characterized. In this study, we found that LUJpv utilizes neither αDG nor hTfR1 as a receptor and found unique characteristics of LUJV glycoprotein in membrane fusion and cell entry. Proper exclusion of cholesterol or some kinds of lipids may play important roles in LUJpv cell entry.",,"['Tani, Hideki', 'Iha, Koichiro', 'Shimojima, Masayuki', 'Fukushi, Shuetsu', 'Taniguchi, Satoshi', 'Yoshikawa, Tomoki', 'Kawaoka, Yoshihiro', 'Nakasone, Naoe', 'Ninomiya, Haruaki', 'Saijo, Masayuki', 'Morikawa, Shigeru']",,,,
,PMC,Ezrin Is a Component of the HIV-1 Virological Presynapse and Contributes to the Inhibition of Cell-Cell Fusion,http://dx.doi.org/10.1128/JVI.00550-14,PMC4054451,,,"During cell-to-cell transmission of HIV-1, viral and cellular proteins transiently accumulate at the contact zone between infected (producer) and uninfected (target) cells, forming the virological synapse. Rearrangements of the cytoskeleton in producer and target cells are required for proper targeting of viral and cellular components during synapse formation, yet little is known about how these processes are regulated, particularly within the producer cell. Since ezrin-radixin-moesin (ERM) proteins connect F-actin with integral and peripheral membrane proteins, are incorporated into virions, and interact with cellular components of the virological presynapse, we hypothesized that they play roles during the late stage of HIV-1 replication. Here we document that phosphorylated (i.e., active) ezrin specifically accumulates at the HIV-1 presynapse in T cell lines and primary CD4(+) lymphocytes. To investigate whether ezrin supports virus transmission, we sought to ablate ezrin expression in producer cells. While cells did not tolerate a complete knockdown of ezrin, even a modest reduction of ezrin expression (∼50%) in HIV-1-producing cells led to the release of particles with impaired infectivity. Further, when cocultured with uninfected target cells, ezrin-knockdown producer cells displayed reduced accumulation of the tetraspanin CD81 at the synapse and fused more readily with target cells, thus forming syncytia. Such an outcome likely is not optimal for virus dissemination, as evidenced by the fact that, in vivo, only relatively few infected cells form syncytia. Thus, ezrin likely helps secure efficient virus spread not only by enhancing virion infectivity but also by preventing excessive membrane fusion at the virological synapse. IMPORTANCE While viruses, in principal, can propagate through successions of syncytia, HIV-1-infected cells in the majority of cases do not fuse with potential target cells during viral transmission. This mode of spread is coresponsible for key features of HIV-1 pathogenesis, including killing of bystander cells and establishment of latently infected T lymphocytes. Here we identify the ERM protein family member ezrin as a cellular factor that contributes to the inhibition of cell-cell fusion and thus to suppressing excessive syncytium formation. Our analyses further suggest that ezrin, which connects integral membrane proteins with actin, functions in concert with CD81, a member of the tetraspanin family of proteins. Additional evidence, documented here and elsewhere, suggests that ezrin and CD81 cooperate to prevent cytoskeleton rearrangements that need to take place during the fusion of cellular membranes.",,"['Roy, Nathan H.', 'Lambelé, Marie', 'Chan, Jany', 'Symeonides, Menelaos', 'Thali, Markus']",,,,
,PMC,Structural Analysis of Respiratory Syncytial Virus Reveals the Position of M2-1 between the Matrix Protein and the Ribonucleoprotein Complex,http://dx.doi.org/10.1128/JVI.00256-14,PMC4054448,,,"Respiratory syncytial virus (RSV), a member of the Paramyxoviridae family of nonsegmented, negative-sense, single-stranded RNA genome viruses, is a leading cause of lower respiratory tract infections in infants, young children, and the elderly or immunocompromised. There are many open questions regarding the processes that regulate human RSV (hRSV) assembly and budding. Here, using cryo-electron tomography, we identified virus particles that were spherical, filamentous, and asymmetric in structure, all within the same virus preparation. The three particle morphologies maintained a similar organization of the surface glycoproteins, matrix protein (M), M2-1, and the ribonucleoprotein (RNP). RNP filaments were traced in three dimensions (3D), and their total length was calculated. The measurements revealed the inclusion of multiple full-length genome copies per particle. RNP was associated with the membrane whenever the M layer was present. The amount of M coverage ranged from 24% to 86% in the different morphologies. Using fluorescence light microscopy (fLM), direct stochastic optical reconstruction microscopy (dSTORM), and a proximity ligation assay (PLA), we provide evidence illustrating that M2-1 is located between RNP and M in isolated viral particles. In addition, regular spacing of the M2-1 densities was resolved when hRSV viruses were imaged using Zernike phase contrast (ZPC) cryo-electron tomography. Our studies provide a more complete characterization of the hRSV virion structure and substantiation that M and M2-1 regulate virus organization. IMPORTANCE hRSV is a leading cause of lower respiratory tract infections in infants and young children as well as elderly or immunocompromised individuals. We used cryo-electron tomography and Zernike phase contrast cryo-electron tomography to visualize populations of purified hRSV in 3D. We observed the three distinct morphologies, spherical, filamentous, and asymmetric, which maintained comparable organizational profiles. Depending on the virus morphology examined, the amount of M ranged from 24% to 86%. We complemented the cryo-imaging studies with fluorescence microscopy, dSTORM, and a proximity ligation assay to provide additional evidence that M2-1 is incorporated into viral particles and is positioned between M and RNP. The results highlight the impact of M and M2-1 on the regulation of hRSV organization.",,"['Kiss, Gabriella', 'Holl, Jens M.', 'Williams, Grant M.', 'Alonas, Eric', 'Vanover, Daryll', 'Lifland, Aaron W.', 'Gudheti, Manasa', 'Guerrero-Ferreira, Ricardo C.', 'Nair, Vinod', 'Yi, Hong', 'Graham, Barney S.', 'Santangelo, Philip J.', 'Wright, Elizabeth R.']",,,,
,PMC,Apolipoprotein D takes center stage in the stress response of the aging and degenerative brain(),http://dx.doi.org/10.1016/j.neurobiolaging.2014.01.148,PMC3988949,24612673,CC BY-NC-ND,"Apolipoprotein D (ApoD) is an ancient member of the lipocalin family with a high degree of sequence conservation from insects to mammals. It is not structurally related to other major apolipoproteins and has been known as a small, soluble carrier protein of lipophilic molecules that is mostly expressed in neurons and glial cells within the central and peripheral nervous system. Recent data indicate that ApoD not only supplies cells with lipophilic molecules, but also controls the fate of these ligands by modulating their stability and oxidation status. Of particular interest is the binding of ApoD to arachidonic acid and its derivatives, which play a central role in healthy brain function. ApoD has been shown to act as a catalyst in the reduction of peroxidized eicosanoids and to attenuate lipid peroxidation in the brain. Manipulating its expression level in fruit flies and mice has demonstrated that ApoD has a favorable effect on both stress resistance and life span. The APOD gene is the gene that is upregulated the most in the aging human brain. Furthermore, ApoD levels in the nervous system are elevated in a large number of neurologic disorders including Alzheimer's disease, schizophrenia, and stroke. There is increasing evidence for a prominent neuroprotective role of ApoD because of its antioxidant and anti-inflammatory activity. ApoD emerges as an evolutionarily conserved anti-stress protein that is induced by oxidative stress and inflammation and may prove to be an effective therapeutic agent against a variety of neuropathologies, and even against aging.",2014 Jul,"['Dassati, Sarah', 'Waldner, Andreas', 'Schweigreiter, Rüdiger']",Neurobiol Aging,,,
,PMC,Time for a neonatal–specific consensus definition for sepsis,http://dx.doi.org/10.1097/PCC.0000000000000157,PMC4087075,,,"OBJECTIVE: To review the accuracy of the pediatric consensus definition of sepsis in term neonates and to determine the definition of neonatal sepsis used. STUDY SELECTION: The review focused primarily on pediatric literature relevant to the topic of interest. CONCLUSIONS: Neonatal sepsis is variably defined based on a number of clinical and laboratory criteria that make the study of this common and devastating condition very difficult. Diagnostic challenges and uncertain disease epidemiology necessarily result from a variable definition of disease. In 2005, intensivists caring for children recognized that as new drugs became available, children would be increasingly studied and thus, pediatric-specific consensus definitions were needed. Pediatric sepsis criteria are not accurate for term neonates and have not been examined in preterm neonates for whom the developmental stage influences aberrations associated with host immune response. Thus, specific consensus definitions for both term and preterm neonates are needed. Such definitions are critical for the interpretation of observational studies, future training of scientists and practitioners, and implementation of clinical trials in neonates.",,"['Wynn, James L.', 'Wong, Hector R.', 'Shanley, Thomas P.', 'Bizzarro, Matthew J.', 'Saiman, Lisa', 'Polin, Richard A.']",,,,
,PMC,Strengthening public health laboratory capacity in Thailand for International Health Regulations (IHR) (2005),,PMC4676564,,,"INTRODUCTION: Thailand conducted a national laboratory assessment of core capacities related to the International Health Regulations (IHR) (2005), and thereby established a baseline to measure future progress. The assessment was limited to public laboratories found within the Thai Bureau of Quality and Safety of Food, National Institute of Health and regional medical science centres. METHODS: The World Health Organization (WHO) laboratory assessment tool was adapted to Thailand through a participatory approach. This adapted version employed a specific scoring matrix and comprised 16 modules with a quantitative output. Two teams jointly performed the on-site assessments in December 2010 over a two-week period, in 17 public health laboratories in Thailand. The assessment focused on the capacity to identify and accurately detect pathogens mentioned in Annex 2 of the IHR (2005) in a timely manner, as well as other public health priority pathogens for Thailand. RESULTS: Performance of quality management, budget and finance, data management and communications was considered strong (>90%); premises quality, specimen collection, biosafety, public health functions, supplies management and equipment availability were judged as very good (>70% but ≤90%); while microbiological capacity, staffing, training and supervision, and information technology needed improvement (>60% but ≤70%). CONCLUSIONS: This assessment is a major step in Thailand towards development of an optimized and standardized national laboratory network for the detection and reporting of infectious disease that would be compliant with IHR (2005). The participatory strategy employed to adapt an international tool to the Thai context can also serve as a model for use by other countries in the Region. The participatory approach probably ensured better quality and ownership of the results, while providing critical information to help decision-makers determine where best to invest finite resources.",,"['Peruski, Anne Harwood', 'Birmingham, Maureen', 'Tantinimitkul, Chawalit', 'Chungsamanukool, Ladawan', 'Chungsamanukool, Preecha', 'Guntapong, Ratigorn', 'Pulsrikarn, Chaiwat', 'Saengklai, Ladapan', 'Supawat, Krongkaew', 'Thattiyaphong, Aree', 'Wongsommart, Duangdao', 'Wootta, Wattanapong', 'Nikiema, Abdoulaye', 'Pierson, Antoine', 'Peruski, Leonard F', 'Liu, Xin', 'Rayfield, Mark A']",,,,
,PMC,The whole iceberg: estimating the incidence of yellow fever virus infection from the number of severe cases,http://dx.doi.org/10.1093/trstmh/tru092,PMC4632853,,,"BACKGROUND: Like many infectious agents, yellow fever (YF) virus only causes disease in a proportion of individuals it infects and severe illness only represents the tip of the iceberg relative to the total number of infections, the more critical factor for virus transmission. METHODS: We compiled data on asymptomatic infections, mild disease, severe disease (fever with jaundice or hemorrhagic symptoms) and fatalities from 11 studies in Africa and South America between 1969 and 2011. We used a Bayesian model to estimate the probability of each infection outcome. RESULTS: For YF virus infections, the probability of being asymptomatic was 0.55 (95% credible interval [CI] 0.37– 0.74), mild disease 0.33 (95% CI 0.13–0.52) and severe disease 0.12 (95% CI 0.05–0.26). The probability of death for people experiencing severe disease was 0.47 (95% CI 0.31–0.62). CONCLUSIONS: In outbreak situations where only severe cases may initially be detected, we estimated that there may be between one and seventy infections that are either asymptomatic or cause mild disease for every severe case identified. As it is generally only the most severe cases that are recognized and reported, these estimates will help improve the understanding of the burden of disease and the estimation of the potential risk of spread during YF outbreaks.",,"['Johansson, Michael A.', 'Vasconcelos, Pedro F. C.', 'Staples, J. Erin']",,,,
,PMC,CANDO and the infinite drug discovery frontier,http://dx.doi.org/10.1016/j.drudis.2014.06.018,PMC4167471,,,"The Computational Analysis of Novel Drug Opportunities (CANDO) platform (http://protinfo.org/cando) uses similarity of compound–proteome interaction signatures to infer homology of compound/drug behavior. We constructed interaction signatures for 3733 human ingestible compounds covering 48,278 protein structures mapping to 2030 indications based on basic science methodologies to predict and analyze protein structure, function, and interactions developed by us and others. Our signature comparison and ranking approach yielded benchmarking accuracies of 12–25% for 1439 indications with at least two approved compounds. We prospectively validated 49/82 ‘high value’ predictions from nine studies covering seven indications, with comparable or better activity to existing drugs, which serve as novel repurposed therapeutics. Our approach may be generalized to compounds beyond those approved by the FDA, and can also consider mutations in protein structures to enable personalization. Our platform provides a holistic multiscale modeling framework of complex atomic, molecular, and physiological systems with broader applications in medicine and engineering.",,"['Minie, Mark', 'Chopra, Gaurav', 'Sethi, Geetika', 'Horst, Jeremy', 'White, George', 'Roy, Ambrish', 'Hatti, Kaushik', 'Samudrala, Ram']",,,,
,PMC,Selecting suitable solid organ transplant donors: Reducing the risk of donor-transmitted infections,http://dx.doi.org/10.5500/wjt.v4.i2.43,PMC4094952,,,"Selection of the appropriate donor is essential to a successful allograft recipient outcome for solid organ transplantation. Multiple infectious diseases have been transmitted from the donor to the recipient via transplantation. Donor-transmitted infections cause increased morbidity and mortality to the recipient. In recent years, a series of high-profile transmissions of infections have occurred in organ recipients prompting increased attention on the process of improving the selection of an appropriate donor that balances the shortage of needed allografts with an approach that mitigates the risk of donor-transmitted infection to the recipient. Important advances focused on improving donor screening diagnostics, using previously excluded high-risk donors, and individualizing the selection of allografts to recipients based on their prior infection history are serving to increase the donor pool and improve outcomes after transplant. This article serves to review the relevant literature surrounding this topic and to provide a suggested approach to the selection of an appropriate solid organ transplant donor.",,"['Jr, Christopher S Kovacs', 'Koval, Christine E', 'van Duin, David', 'de Morais, Amanda Guedes', 'Gonzalez, Blanca E', 'Avery, Robin K', 'Mawhorter, Steven D', 'Brizendine, Kyle D', 'Cober, Eric D', 'Miranda, Cyndee', 'Shrestha, Rabin K', 'Teixeira, Lucileia', 'Mossad, Sherif B']",,,,
,PMC,Modified Newcastle disease virus vectors expressing the H5 hemagglutinin induce enhanced protection against highly pathogenic H5N1 avian influenza virus in chickens,http://dx.doi.org/10.1016/j.vaccine.2014.06.061,PMC4794254,,,"Naturally-occurring attenuated strains of Newcastle disease virus (NDV) are being developed as vaccine vectors for use in poultry and humans. However, some NDV strains, such as Beaudette C (BC), may retain too much virulence in poultry for safe use, and more highly attenuated strains may be suboptimally immunogenic. We therefore modified the BC strain by changing the multibasic cleavage site sequence of the F protein to the dibasic sequence of avirulent strain LaSota. Additionally, the BC, F, and HN proteins were modified in several ways to enhance virus replication. These modified BC-derived vectors and the LaSota strain were engineered to express the hemagglutin (HA) protein of H5N1 highly pathogenic influenza virus (HPAIV). In general, the modified BC-based vectors expressing HA replicated better than LaSota/HA, and expressed higher levels of HA protein. Pathogenicity tests indicated that all the modified viruses were highly attenuated in chickens. Based on in vitro characterization, two of the modified BC vectors were chosen for evaluation in chickens as vaccine vectors against H5N1 HPAIV A/Vietnam/1203/04. Immunization of chickens with rNDV vector vaccines followed by challenge with HPAIV demonstrated high levels of protection against clinical disease and mortality. However, only those chickens immunized with modified BC/HA in which residues 271–330 from the F protein had been replaced with the corresponding sequence from the NDV AKO strain conferred complete protection against challenge virus shedding. Our findings suggest that this modified rNDV can be used safely as a vaccine vector with enhanced replication, expression, and protective efficacy in avian species, and potentially in humans.",,"['Kim, Shin-Hee', 'Paldurai, Anandan', 'Xiao, Sa', 'Collins, Peter L.', 'Samal, Siba K.']",,,,
,PMC,Progress and outlook in structural biology of large viral RNAs,http://dx.doi.org/10.1016/j.virusres.2014.06.007,PMC4252365,,,"The field of viral molecular biology has reached a precipice for which pioneering studies on the structure of viral RNAs are beginning to bridge the gap. It has become clear that viral genomic RNAs are not simply carriers of hereditary information, but rather are active players in many critical stages during replication. Indeed, functions such as cap-independent translation initiation mechanisms are, in some cases, primarily driven by RNA structural determinants. Other stages including reverse transcription initiation in retroviruses, nuclear export and viral packaging are specifically dependent on the proper 3-dimensional folding of multiple RNA domains to recruit necessary viral and host factors required for activity. Furthermore, a large-scale conformational change within the 5′-untranslated region of HIV-1 has been proposed to regulate the temporal switch between viral protein synthesis and packaging. These RNA-dependent functions are necessary for replication of many human disease-causing viruses such as severe acute respiratory syndrome (SARS)-associated coronavirus, West Nile virus, and HIV-1. The potential for antiviral development is currently hindered by a poor understanding of RNA-driven molecular mechanisms, resulting from a lack of structural information on large RNAs and ribonucleoprotein complexes. Herein, we describe the recent progress that has been made on characterizing these large RNAs and provide brief descriptions of the techniques that will be at the forefront of future advances. Ongoing and future work will contribute to a more complete understanding of the lifecycles of retroviruses and RNA viruses and potentially lead to novel antiviral strategies.",,"['Cantara, William A.', 'Olson, Erik D.', 'Forsyth, Karin Musier']",,,,
,PMC,Evaluating Weight of Evidence in the Mystery of Balkan Endemic Nephropathy,http://dx.doi.org/10.1111/risa.12239,PMC4199864,,,"Balkan Endemic Nephropathy (BEN) is a chronic, progressive wasting disease of the kidneys, endemic in certain rural regions of the Balkan nations Croatia, Serbia, Bulgaria, and Romania. It is irreversible, and ultimately fatal. Though this disease was first described in the 1920s, its causes have been a mystery and a source of much academic and clinical contention. Possible etiologic agents that have been explored include exposure to metals and metalloids, viruses and bacteria, and the environmental toxins aristolochic acid (AA) and ochratoxin A (OTA). Aristolochic acid is a toxin produced by weeds of the genus Aristolochia, common in Balkan wheat fields. Aristolochia seeds may intermingle with harvested grains and thus inadvertently enter human diets. Ochratoxin A is a mycotoxin (fungal toxin) common in many foods, including cereal grains. In this study, we analyzed the weight of evidence for each of the suspected causes of BEN using the Bradford Hill Criteria (BHC): nine conditions that determine weight of evidence for a causal relationship between an agent and a disease. Each agent postulated to cause BEN was evaluated using the nine criteria, and for each criterion was given a rating based on the strength of the association between exposure to the substance and BEN. From the overall available scientific evidence for each of these suspected risk factors, aristolochic acid is the agent with the greatest weight of evidence in causing BEN. We describe other methods for testing causality from epidemiological studies, which support this conclusion of AA causing BEN.",,"['Bui-Klimke, Travis', 'Wu, Felicia']",,,,
,PMC,Resilience of biochemical activity in protein domains in the face of structural divergence,http://dx.doi.org/10.1016/j.sbi.2014.05.008,PMC5915356,,,"Recent studies point to the prevalence of the evolutionary phenomenon of drastic structural transformation of protein domains while continuing to preserve their basic biochemical function. These transformations span a wide spectrum, including simple domains incorporated into larger structural scaffolds, changes in the structural core, major active site shifts, topological rewiring and extensive structural transmogrifications. Proteins from biological conflict systems, such as toxinantitoxin, restriction-modification, CRISPR/Cas, polymorphic toxin and secondary metabolism systems commonly display such transformations. These include endoDNases, metal-independent RNases, deaminases, ADP ribosyltransferases, immunity proteins, kinases and E1-like enzymes. In eukaryotes such transformations are seen in domains involved in chromatin-related peptide recognition and protein/DNA-modification. Intense selective pressures from “arm-race”-like situations in conflict and macromolecular modification systems could favor drastic structural divergence while preserving function.",,"['Zhang, Dapeng', 'Iyer, Lakshminarayan M.', 'Burroughs, A. Maxwell', 'Aravind, L.']",,,,
,PMC,Mutagenesis Studies of the H5 Influenza Hemagglutinin Stem Loop Region,http://dx.doi.org/10.1074/jbc.M114.572974,PMC4139235,,,"Influenza outbreaks, particularly the pandemic 1918 H1 and avian H5 strains, are of high concern to public health. The hemagglutinin envelope protein of influenza plays a critical role in viral entry and thus is an attractive target for inhibition of virus entry. The highly conserved stem loop region of hemagglutinin has been shown to undergo critically important conformational changes during the entry process and, moreover, to be a site for inhibition of virus entry by antibodies, small proteins, and small drug-like molecules. In this work we probe the structure-function properties of the H5 hemagglutinin stem loop region by site-directed mutagenesis. We find that most mutations do not disrupt expression, proteolytic processing, incorporation into virus, or receptor binding; however, many of the mutations disrupt the entry process. We further assess the effects of mutations on inhibition of entry by a neutralizing monoclonal antibody (C179) and find examples of increased and decreased sensitivity to the antibody, consistent with the antibody binding site observed by x-ray crystallography. In addition, we tested the sensitivity of the mutants to MBX2329, a small molecule inhibitor of influenza entry. Interestingly, the mutants exhibit increased and decreased sensitivities to MBX2329, which gives further insight into the binding site of the compound on HA and potential mechanisms of escape. Finally, we have modeled the binding site of MBX2329 using molecular dynamics and find that the resulting structure is in good agreement with the mutagenesis results. Together these studies underscore the importance of the stem loop region to HA function and suggest potential sites for therapeutic intervention of influenza entry.",,"['Antanasijevic, Aleksandar', 'Basu, Arnab', 'Bowlin, Terry L.', 'Mishra, Rama K.', 'Rong, Lijun', 'Caffrey, Michael']",,,,
,PMC,Diagnostic problems related to acute fibrinous and organizing pneumonia: misdiagnosis in 2 cases of lung consolidation and occupying lesions,,PMC4129075,,,"Acute fibrinous and organizing pneumonia (AFOP) is a histological pattern characterized by intra-alveolus fibrinous deposition accompanied with a spectrum of clinical condition. It also presents in other types of lung lesions, thus renders risks to its diagnosis with small biopsies. Here we present 2 cases of lung consolidation and occupying lesions with typical histological presentation of AFOP. One case is tuberculosis presented as massive lung consolidation, initially treated as AFOP, and eventually progressed to bilateral military tuberculosis. The other case presented an occupying mass in the lung which was initially suspected to be an inflammatory mass with AFOP. Lobectomy revealed a poorly-differentiated adenocarcinoma, with AFOP pattern present in the peripheral tissues of the neoplastic mass. In conclusion, we suggest that it is not preferable to diagnose idiopathic AFOP in lung consolidation and occupying lesions before excluding other types of lesions. The diagnostic significance of AFOP should be deliberated.",,"['Feng, An-Ning', 'Cai, Hou-Rong', 'Zhou, Qiang', 'Zhang, Yi-Fen', 'Meng, Fan-Qing']",,,,
,PMC,Sero-epidemiology of MERS coronavirus in Saudi Arabia (1993) and Australia (2014) and characterization of assay specificity,,PMC4674219,,,Pseudoparticle virus neutralization (ppNT) and a conventional microneutralization (MN) assays are specific for detecting antibodies to MERS coronavirus (MERS-CoV) when used in sero-epidemiological studies in animals. Genetically diverse MERS-CoV appear antigenically similar in MN tests. We confirm that MERS-CoV has been circulating in dromedaries in Saudi Arabia in 1993. Preliminary data suggests that feral Australian dromedaries may be free of MERS-CoV but larger confirmatory studies are needed.,,"['Hemida, MG', 'Perera, RAPM', 'Al Jassim, RAM', 'Kayali, G', 'Siu, LY', 'Wang, P', 'Chu, DKW', 'Perlman, S', 'Ali, MA', 'Alnaeem, A', 'Poon, LLM', 'Saif, L', 'Peiris, M']",,,,
,PMC,Annotation of long non-coding RNAs expressed in Collaborative Cross founder mice in response to respiratory virus infection reveals a new class of interferon-stimulated transcripts,http://dx.doi.org/10.4161/rna.29442,PMC4179962,,,"The outcome of respiratory virus infection is determined by a complex interplay of viral and host factors. Some potentially important host factors for the antiviral response, whose functions remain largely unexplored, are long non-coding RNAs (lncRNAs). Here we systematically inferred the regulatory functions of host lncRNAs in response to influenza A virus and severe acute respiratory syndrome coronavirus (SARS-CoV) based on their similarity in expression with genes of known function. We performed total RNA-Seq on viral-infected lungs from eight mouse strains, yielding a large data set of transcriptional responses. Overall 5,329 lncRNAs were differentially expressed after infection. Most of the lncRNAs were co-expressed with coding genes in modules enriched in genes associated with lung homeostasis pathways or immune response processes. Each lncRNA was further individually annotated using a rank-based method, enabling us to associate 5,295 lncRNAs to at least one gene set and to predict their potential cis effects. We validated the lncRNAs predicted to be interferon-stimulated by profiling mouse responses after interferon-α treatment. Altogether, these results provide a broad categorization of potential lncRNA functions and identify subsets of lncRNAs with likely key roles in respiratory virus pathogenesis. These data are fully accessible through the MOuse NOn-Code Lung interactive database (MONOCLdb).",,"['Josset, Laurence', 'Tchitchek, Nicolas', 'Gralinski, Lisa E', 'Ferris, Martin T', 'Eisfeld, Amie J', 'Green, Richard R', 'Thomas, Matthew J', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P', 'Kawaoka, Yoshihiro', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S', 'Heise, Mark T', 'Peng, Xinxia', 'Katze, Michael G']",,,,
,PMC,CORONAVIRUS REVERSE GENETIC SYSTEMS: INFECTIOUS CLONES AND REPLICONS,http://dx.doi.org/10.1016/j.virusres.2014.05.026,PMC4727449,,,"Coronaviruses (CoVs) infect humans and many animal species, and are associated with respiratory, enteric, hepatic, and central nervous system diseases. The large size of the CoV genome and the instability of some CoV replicase gene sequences during its propagation in bacteria, represent serious obstacles for the development of reverse genetic systems similar to those used for smaller positive sense RNA viruses. To overcome these limitations, several alternatives to more conventional plasmid-based approaches have been established in the last thirteen years. In this report, we briefly review and discuss the different reverse genetic systems developed for CoVs, paying special attention to the severe acute respiratory syndrome CoV (SARS-CoV).",,"['Almazán, Fernando', 'Sola, Isabel', 'Zuñiga, Sonia', 'Marquez-Jurado, Silvia', 'Morales, Lucia', 'Becares, Martina', 'Enjuanes, Luis']",,,,
,PMC,"MERS differs from SARS, say experts",http://dx.doi.org/10.1503/cmaj.109-4798,PMC4050010,,,,,"Brown, Carolyn",,,,
,PMC,Neurobiology of microglial action in CNS injuries: receptor-mediated signaling mechanisms and functional roles,http://dx.doi.org/10.1016/j.pneurobio.2014.06.002,PMC4121732,,,"Microglia are the first line of immune defense against central nervous system (CNS) injuries and disorders. These highly plastic cells play dualistic roles in neuronal injury and recovery and are known for their ability to assume diverse phenotypes. A broad range of surface receptors are expressed on microglia and mediate microglial ‘On’ or ‘Off’ responses to signals from other host cells as well as invading microorganisms. The integrated actions of these receptors result in tightly regulated biological functions, including cell mobility, phagocytosis, the induction of acquired immunity, and trophic factor/inflammatory mediator release. Over the last few years, significant advances have been made towards deciphering the signaling mechanisms related to these receptors and their specific cellular functions. In this review, we describe the current state of knowledge of the surface receptors involved in microglial activation, with an emphasis on their engagement of distinct functional programs and their roles in CNS injuries. It will become evident from this review that microglial homeostasis is carefully maintained by multiple counterbalanced strategies, including, but not limited to, ‘On’ and ‘Off’ receptor signaling. Specific regulation of theses microglial receptors may be a promising therapeutic strategy against CNS injuries.",,"['Hu, Xiaoming', 'Liou, Anthony K.F.', 'Leak, Rehana K.', 'Xu, Mingyue', 'An, Chengrui', 'Suenaga, Jun', 'Shi, Yejie', 'Gao, Yanqin', 'Zheng, Ping', 'Chen, Jun']",,,,
,PMC,Discovery of a new antiviral protein isolated Lonomia obliqua analysed by bioinformatics and real-time approaches,http://dx.doi.org/10.1007/s10616-014-9740-1,PMC4628924,,,"This study presents a new recombinant protein that acts as a powerful antiviral (rAVLO—recombinant Antiviral protein of Lonomia obliqua). It was able to reduce the replication by 10(6) fold for herpes virus and by 10(4) fold for rubella virus. RT-PCR of viral RNA rAVLO treated infected cells also showed similar rate of inhibition in replication. The analysis of this protein by bioinformatics suggests that this protein is globular, secreted with a signal peptide and has the ability to bind to MHC class I. It was found that there are several protein binding sites with various HLA and a prevalence of α-helices in the N-terminal region (overall classified as a α/β protein type). BLAST similarity sequence search for corresponding cDNA did not reveal a similar sequence in Genbank, suggesting that it is from a novel protein family. In this study we have observed that this recombinant protein and hemolymph has a potent antiviral action. This protein was produced in a baculovirus/Sf-9 system. Therefore, these analyses suggest that this novel polypeptide is a candidate as a broad spectrum antiviral.",,"['Carmo, Ana Carolina Viegas', 'Yamasaki, Lilian Hiromi Tomanari', 'Figueiredo, Cristina Adelaide', 'da Silva Giovanni, Dalton Nogueira', 'de Oliveira, Maria Isabel', 'dos Santos, Fabiana Cristina Pereira', 'Curti, Suely Pires', 'Rahal, Paula', 'Mendonça, Ronaldo Zucatelli']",,,,
,PMC,Frequency of Acute Respiratory Illnesses and Circulation of Respiratory Viruses in Households With Children Over 3 Surveillance Seasons,http://dx.doi.org/10.1093/infdis/jiu327,PMC4296188,,,"Background. The household has traditionally been the site for studying acute respiratory illnesses (ARIs). Most studies were conducted many years ago, and more broadly sensitive laboratory methods to determine ARI etiology are now available. Methods. We recruited and followed households with children over 3 annual surveillance periods and collected respiratory tract specimens from subjects with reported ARI. Virus etiology was determined by real-time reverse-transcription polymerase chain reaction (RT-PCR) analysis. Results. Individuals in larger households (defined as households with >4 members) and those in households with children aged <5 years had significantly higher ARI frequencies than others. ARI frequency generally declined with increasing age. Virus etiology was most likely to be determined in young children, who were also most likely to have virus coinfection. Overall, 16% of ARIs with 1 virus identified had ≥1 coinfecting virus. Rhinoviruses and coronaviruses were the most frequently identified agents of ARI in all age categories. Influenza virus and adenovirus were less frequently identified but were most likely to cause ARI that required medical attention. Conclusions. Longitudinal studies in families remain a valuable way to study respiratory infections. RT-PCR has increased the sensitivity of virus detection, including coinfecting viruses, and expanded our ability to detect viruses now known to cause ARI.",,"['Monto, Arnold S.', 'Malosh, Ryan E.', 'Petrie, Joshua G.', 'Thompson, Mark G.', 'Ohmit, Suzanne E.']",,,,
,PMC,Identification Of Novel Functional Regions Within The Spike Glycoprotein Of MHV-A59 Based On A Bioinformatics Approach,http://dx.doi.org/10.1016/j.virusres.2014.05.023,PMC4134989,,,"Mouse Hepatitis Virus (MHV) is a single-stranded positive sense RNA virus with the ability to promote acute and chronic diseases in mice. The MHV spike protein (S) is a major virulence determinant which in addition to binding to cellular receptors to mediate cell entry and facilitate virus spread to adjacent cells by cell-cell fusion, also is a molecular mimic of the FcγRII receptor. This molecular mimicry of FcγRII by the MHV S protein is also exhibited by other lineage 2a betacoronaviruses, with the exception of the human coronavirus HCoV-OC43. In this work we undertook a mutational analysis to attempt to identify specific amino acid sequences within the spike glycoprotein crucial for molecular mimicry of FcγRII. Although we were unsuccessful in isolating mutant viruses which were specifically defective in that property, we identified several mutations with interesting phenotypes. Mutation of the cysteine in position 547 to alanine and alanine replacements at residues 581–586 was lethal. Replacing proline 939 with the corresponding HCoV-OC43 residue, leucine, decreased the ability MHV to induce cell-cell fusion, providing experimental support for an earlier proposal that residues 929–944 make up the fusion peptide of the MHV S protein.",,"['Kaufman, Gili', 'Liu, Pinghua', 'Leibowitz, Julian L.']",,,,
,PMC,Severe Neutropenia in Dengue Patients: Prevalence and Significance,http://dx.doi.org/10.4269/ajtmh.14-0004,PMC4047758,,,"Studies on severe neutropenia in dengue are scarce, and its clinical significance is uncertain. We analyzed a cohort of 1,921 reverse transcription polymerase chain reaction-confirmed adult dengue patients admitted to the Communicable Disease Center in Singapore between 2005 and 2008. Time trend analyses for daily absolute neutrophil counts (ANCs) were done using Bayesian hierarchical and Markov models. We found that severe neutropenia, defined as ANC ≤ 0.5 × 10(9)/L, was found in 11.8% with a median duration of 1 day. ANC nadir occurred on illness day 5. Severe neutropenia was not predictive of more severe disease and not associated with secondary bacterial infections, prolonged hospital stay, prolonged fever, or fatal outcome. We concluded that prophylactic antibiotics are not indicated in patients with severe neutropenia without indication for bacterial infection.",,"['Thein, Tun-Linn', 'Lye, David C.', 'Leo, Yee-Sin', 'Wong, Joshua G. X.', 'Hao, Ying', 'Wilder-Smith, Annelies']",,,,
,PMC,Glial cells suppress post-encephalitic CD8(+) T lymphocytes through PD-L1,http://dx.doi.org/10.1002/glia.22701,PMC4141010,,,"Engagement of the programmed death (PD)-1 receptor on activated cells by its ligand (PD-L1) is a mechanism for suppression of activated T-lymphocytes. Microglia, the resident inflammatory cells of the brain, are important for pathogen detection and initiation of innate immunity, however, a novel role for these cells as immune regulators has also emerged. PD-L1 on microglia has been shown to negatively regulate T-cell activation in models of multiple sclerosis and acute viral encephalitis. In this study, we investigated the role of glial cell PD-L1 in controlling encephalitogenic CD8(+) T-lymphocytes, which infiltrate the brain to manage viral infection, but remain to produce chronic neuroinflammation. Using a model of chronic neuroinflammation following murine cytomegalovirus (MCMV)-induced encephalitis, we found that CD8(+) T-cells persisting within the brain expressed PD-1. Conversely, activated microglia expressed PD-L1. In vitro, primary murine microglia, which express low basal levels of PD-L1, upregulated the co-inhibitory ligand upon IFN-γ-treatment. Blockade of the PD-1: PD-L1 pathway in microglial: CD8(+) T-cell co-cultures increased T-cell IFN-γ and interleukin (IL)-2 production. We observed a similar phenomenon following blockade of this co-inhibitory pathway in astrocyte: CD8(+) T-cell co-cultures. Using ex vivo cultures of brain leukocytes, including microglia and CD8(+) T-cells, obtained from mice with MCMV-induced chronic neuroinflammation, we found that neutralization of either PD-1 or PD-L1 increased IFN-γ production from virus-specific CD8(+) T-cells stimulated with MCMV IE1(168-176) peptide. These data demonstrate that microglia and astrocytes control antiviral T-cell responses and suggest a therapeutic potential of PD1: PD-L1 modulation to manage the deleterious consequences of uncontrolled neuroinflammation.",,"['Schachtele, Scott J.', 'Hu, Shuxian', 'Sheng, Wen S.', 'Mutnal, Manohar B.', 'Lokensgard, James R.']",,,,
,PMC,The Art of War: battles between virus and host,http://dx.doi.org/10.1016/j.coviro.2014.05.001,PMC4422063,,,"As Sun Tzu wrote in The Art of War, “All warfare is based on deception”. He could have easily been describing the ancient battle between virus and host rather than on the lore of Chinese warfare. A virus must infect, replicate and spread for it to survive; the host attempting to thwart it at every step of the way. This ancient battle has been waged for millions of years and has spawned an innumerable number of viruses, each with their own unique ways of trying to outsmart the host. Some viruses encode proteins that directly inhibit/degrade/alter host pathways and some simply have evolved ways to hide from the hosts detection system. The host is not passive in this battle. It has evolved complex pathways and redundant mechanisms to respond to viral interlopers.",,"Frieman, Matthew",,,,
,PMC,IL-27 Limits Central Nervous System Viral Clearance by Promoting IL-10 and Enhances Demyelination,http://dx.doi.org/10.4049/jimmunol.1400058,PMC4067872,,,"IL-27 is a pleiotropic member of the IL-6 and IL-12 cytokine family composed of the IL-27p28 and the EBV-induced gene 3. IL-27 and its receptor mRNA are both upregulated in the CNS during acute encephalomyelitis induced by the JHM strain of mouse hepatitis virus (JHMV) and sustained during viral persistence. Contributions of IL-27 to viral pathogenesis were evaluated by infection of IL-27Rα-chain–deficient (IL-27Rα(−/−)) mice. The absence of IL-27 signaling accelerated virus control within the CNS associated with increased IFN-γ secreting virus-specific CD4(+) and CD8(+) T cells. Abrogation of IL-27 signaling did not affect virus-specific CD8(+) T cell–mediated IL-10 production or cytolytic activity or Foxp3(+) regulatory T cell populations. However, IL-10 production by virus-specific CD4(+) T cells was reduced significantly. Despite increased T cell–mediated antiviral function in IL-27Rα(−/−) mice, the virus persisted in the CNS at similar levels as in wild-type mice. Nevertheless, IL-27Rα(−/−) mice exhibited decreased clinical disease during persistence, coincident with less severe demyelination, the hallmark tissue damage associated with JHMV infection. Overall, these data demonstrate that in contrast to viral infections at other sites, IL-27 does not play a proinflammatory role during JHMV-induced encephalomyelitis. Rather, it limits CNS inflammation and impairs control of CNS virus replication via induction of IL-10 in virus-specific CD4(+) T cells. Furthermore, in contrast to its protective role in limiting CNS autoimmunity and preventing immunopathology, these data define a detrimental role of IL-27 in promoting demyelination by delaying viral control.",,"['de Aquino, Maria Teresa P.', 'Kapil, Parul', 'Hinton, David R.', 'Phares, Timothy W.', 'Puntambekar, Shweta S.', 'Savarin, Carine', 'Bergmann, Cornelia C.', 'Stohlman, Stephen A.']",,,,
,PMC,Modulation of Airway Epithelial Antiviral Immunity by Fungal Exposure,http://dx.doi.org/10.1165/rcmb.2013-0357OC,PMC4068913,,,"Multiple pathogens, such as bacteria, fungi, and viruses, have been frequently found in asthmatic airways and are associated with the pathogenesis and exacerbation of asthma. Among these pathogens, Alternaria alternata (Alt), a universally present fungus, and human rhinovirus have been extensively studied. However, their interactions have not been investigated. In the present study, we tested the effect of Alt exposure on virus-induced airway epithelial immunity using live virus and a synthetic viral mimicker, double-stranded RNA (dsRNA). Alt treatment was found to significantly enhance the production of proinflammatory cytokines (e.g., IL-6 and IL-8) induced by virus infection or dsRNA treatment. In contrast to this synergistic effect, Alt significantly repressed type I and type III IFN production, and this impairment led to elevated viral replication. Mechanistic studies suggested the positive role of NF-κB and mitogen-activated protein kinase pathways in the synergism and the attenuation of the TBK1-IRF3 pathway in the inhibition of IFN production. These opposite effects are caused by separate fungal components. Protease-dependent and -independent mechanisms appear to be involved. Thus, Alt exposure alters the airway epithelial immunity to viral infection by shifting toward more inflammatory but less antiviral responses.",,"['Zhu, Lingxiang', 'Lee, Boram', 'Zhao, Fangkun', 'Zhou, Xu', 'Chin, Vanessa', 'Ling, Serena C.', 'Chen, Yin']",,,,
,PMC,"Preclinical Characterization of BMS-791325, an Allosteric Inhibitor of Hepatitis C Virus NS5B Polymerase",http://dx.doi.org/10.1128/AAC.02495-13,PMC4068470,,,"BMS-791325 is an allosteric inhibitor that binds to thumb site 1 of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. BMS-791325 inhibits recombinant NS5B proteins from HCV genotypes 1, 3, 4, and 5 at 50% inhibitory concentrations (IC(50)) below 28 nM. In cell culture, BMS-791325 inhibited replication of HCV subgenomic replicons representing genotypes 1a and 1b at 50% effective concentrations (EC(50)s) of 3 nM and 6 nM, respectively, with similar (3 to 18 nM) values for genotypes 3a, 4a, and 5a. Potency against genotype 6a showed more variability (9 to 125 nM), and activity was weaker against genotype 2 (EC(50), 87 to 925 nM). Specificity was demonstrated by the absence of activity (EC(50)s of >4 μM) against a panel of mammalian viruses, and cytotoxic concentrations (50%) were >3,000-fold above the HCV EC(50). Resistance substitutions selected by BMS-791325 in genotype 1 replicons mostly mapped to a single site, NS5B amino acid 495 (P495A/S/L/T). Additive or synergistic activity was observed in combination studies using BMS-791325 with alfa interferon plus ribavirin, inhibitors of NS3 protease or NS5A, and other classes of NS5B inhibitor (palm site 2-binding or nucleoside analogs). Plasma and liver exposures in vivo in several animal species indicated that BMS-791325 has a hepatotropic disposition (liver-to-plasma ratios ranging from 1.6- to 60-fold across species). Twenty-four hours postdose, liver exposures across all species tested were ≥10-fold above the inhibitor EC(50)s observed with HCV genotype 1 replicons. These findings support the evaluation of BMS-791325 in combination regimens for the treatment of HCV. Phase 3 studies are ongoing.",,"['Lemm, Julie A.', 'Liu, Mengping', 'Gentles, Robert G.', 'Ding, Min', 'Voss, Stacey', 'Pelosi, Lenore A.', 'Wang, Ying-Kai', 'Rigat, Karen L.', 'Mosure, Kathleen W.', 'Bender, John A.', 'Knipe, Jay O.', 'Colonno, Richard', 'Meanwell, Nicholas A.', 'Kadow, John F.', 'Santone, Kenneth S.', 'Roberts, Susan B.', 'Gao, Min']",,,,
,PMC,Chromosomal Insertions in the Lactobacillus casei upp Gene That Are Useful for Vaccine Expression,http://dx.doi.org/10.1128/AEM.00175-14,PMC4018855,,,"To develop a stable and marker-free Lactobacillus strain useful for the expression of vaccines, we developed a temperature-sensitive suicide plasmid with expression cassettes containing an HCE promoter, a PgsA anchor, the alpha-toxin gene, and an rrnB T1T2 terminator (PPαT) that uses a 5-fluorouracil (5-FU) counterselectable marker for Lactobacillus casei. Three strains containing the correct PPαT expression cassettes were produced via the selective pressure of 5-FU screening. We confirmed that the upp gene was deleted and that the PPαT expression cassettes were inserted into the upp site of L. casei ATCC 393 by genomic PCR amplification and sequencing. 5-FU resistance in recombinant bacteria could be stably inherited for as long as 40 generations following insertion. However, bacteria containing the integrated DNA grew more slowly than wild-type L. casei. An indirect enzyme-linked immunosorbent assay (ELISA) analysis demonstrated that the alpha-toxin gene was expressed. Also, we visualized expression of the protein on the surface of L. casei cells using laser confocal microscopy. These results taken together demonstrate that these recombinant bacteria should provide a safe tool for effective vaccine production.",,"['Song, Bai-fen', 'Ju, Long-zhu', 'Li, Yi-jing', 'Tang, Li-jie']",,,,
,PMC,Tuberculosis in BRICS: challenges and opportunities for leadership within the post-2015 agenda,http://dx.doi.org/10.2471/BLT.13.133116,PMC4047808,,,,,"['Creswell, Jacob', 'Sahu, Suvanand', 'Sachdeva, Kuldeep Singh', 'Ditiu, Lucica', 'Barreira, Draurio', 'Mariandyshev, Andrei', 'Mingting, Chen', 'Pillay, Yogan']",,,,
,PMC,Relative health performance in BRICS over the past 20 years: the winners and losers,http://dx.doi.org/10.2471/BLT.13.132480,PMC4047803,,,"OBJECTIVE: To determine whether the health performance of Brazil, the Russian Federation, India, China and South Africa – the countries known as BRICS – has kept in step with their economic development. METHODS: Reductions in age- and sex-specific mortality seen in each BRICS country between 1990 and 2011 were measured. These results were compared with those of the best-performing countries in the world and the best-performing countries with similar income levels. We estimated each country’s progress in reducing mortality and compared changes in that country’s mortality rates against other countries with similar mean incomes to examine changes in avoidable mortality. FINDINGS: The relative health performance of the five study countries differed markedly over the study period. Brazil demonstrated fairly even improvement in relative health performance across the different age and sex subgroups that we assessed. India’s improvement was more modest and more varied across the subgroups. South Africa and the Russian Federation exhibited large declines in health performance as well as large sex-specific inequalities in health. Although China’s levels of avoidable mortality decreased in absolute terms, the level of improvement appeared low in the context of China’s economic growth. CONCLUSION: When evaluating a country’s health performance in terms of avoidable mortality, it is useful to compare that performance against the performance of other countries. Such comparison allows any country-specific improvements to be distinguished from general global improvements.",,"['Petrie, Dennis', 'Tang, Kam Ki']",,,,
,PMC,Interferon Gene Expression in Sputum Cells Correlates with the Asthma Index Score During Virus-Induced Exacerbations,http://dx.doi.org/10.1111/cea.12269,PMC4037351,,,"RATIONALE: The majority of asthma exacerbations are related to viral respiratory infections. Some, but not all, previous studies have reported that low interferon responses in patients with asthma increase the risk for virus-induced exacerbations. OBJECTIVE: We sought to determine the relationship between lower airway inflammatory biomarkers, specifically interferon gene expression, and the severity or presence of an exacerbation in asthmatics experiencing a naturally occurring viral infection. METHODS: Sputum samples were analyzed from subjects in an asthma exacerbation study who experienced a confirmed viral infection. Subjects were monitored for daily symptoms, medication use, and peak expiratory flow rate until baseline. Sputum samples were assessed for cell counts and gene expression. RESULTS: IFN-γ expression was significantly greater in patients with asthma exacerbations compared to non-exacerbating patients (p=0.002). IFN-α1, IFN-β1, and IFN-γ mRNA levels correlated with the peak Asthma Index (r=0.58, p<0.001; r=0.57, p=0.001; and r=0.51, p=0.004, respectively). Additionally, IL-13, IL-10 and eosinophil major basic protein mRNA levels were greater in patients with asthma exacerbations compared to non-exacerbating patients (p=0.03, p=0.06, and p=0.02, respectively), and IL-13 mRNA correlated with the peak Asthma Index (p=0.006). CONCLUSIONS: Our findings indicate that asthma exacerbations are associated with increased rather than decreased expression of interferons early in the course of infection. These findings raise the possibility that excessive virus-induced interferon production during acute infections can contribute to airway inflammation and exacerbations of asthma.",,"['Schwantes, Elizabeth A.', 'Manthei, David M.', 'Denlinger, Loren C.', 'Evans, Michael D.', 'Gern, James E.', 'Jarjour, Nizar N.', 'Mathur, Sameer K.']",,,,
,PMC,Seroepidemiology of Astrovirus MLB1,http://dx.doi.org/10.1128/CVI.00100-14,PMC4054231,,,"To determine the seroprevalence of astrovirus MLB1 (MLB1), an indirect enzyme-linked immunosorbent assay (ELISA) was established. MLB1 seropositivity was high in children <6 months old, decreased to a nadir at 12 to 23 months old, and increased to 100% by adulthood. MLB1 infection is common, and primary exposure occurs in childhood.",,"['Holtz, Lori R.', 'Bauer, Irma K.', 'Jiang, Hongbing', 'Belshe, Robert', 'Freiden, Pamela', 'Schultz-Cherry, Stacey L.', 'Wang, David']",,,,
,PMC,Detecting Specific Infections in Children through Host Responses: A Paradigm Shift,http://dx.doi.org/10.1097/QCO.0000000000000065,PMC4137468,,,"PURPOSE OF THE REVIEW: There is a need for improved diagnosis and for optimal classification of patients with infectious diseases. An alternative approach to the pathogen-detection strategy is based on a comprehensive analysis of the host response to the infection. This review focuses on the value of transcriptome analyses of blood leukocytes for the diagnosis and management of patients with infectious diseases. RECENT FINDINGS: Initial studies showed that RNA from blood leukocytes of children with acute viral and bacterial infections carried pathogen-specific transcriptional signatures. Subsequently, transcriptional signatures for several other infections have been described and validated in humans with malaria, dengue, salmonella, meloidosis, RSV, influenza, tuberculosis and HIV. In addition, transcriptome analyses represent an invaluable tool to understand disease pathogenesis, and to objectively classify patients according to clinical severity. SUMMARY: Microarray studies have shown to be highly reproducible using different platforms, and in different patient populations, confirming the value of blood transcriptome analyses to study pathogen-specific host immune responses in the clinical setting. Combining the detection of the pathogen with a comprehensive assessment of the host immune response will provide a new understanding of the correlations between specific etiologic agents, the host response and the clinical manifestations of the disease.",,"['Mejias, Asuncion', 'Suarez, Nicolas M.', 'Ramilo, Octavio']",,,,
,PMC,OutbreakTools: A new platform for disease outbreak analysis using the R software,http://dx.doi.org/10.1016/j.epidem.2014.04.003,PMC4058532,24928667,CC BY,"The investigation of infectious disease outbreaks relies on the analysis of increasingly complex and diverse data, which offer new prospects for gaining insights into disease transmission processes and informing public health policies. However, the potential of such data can only be harnessed using a number of different, complementary approaches and tools, and a unified platform for the analysis of disease outbreaks is still lacking. In this paper, we present the new R package OutbreakTools, which aims to provide a basis for outbreak data management and analysis in R. OutbreakTools is developed by a community of epidemiologists, statisticians, modellers and bioinformaticians, and implements classes and methods for storing, handling and visualizing outbreak data. It includes real and simulated outbreak datasets. Together with a number of tools for infectious disease epidemiology recently made available in R, OutbreakTools contributes to the emergence of a new, free and open-source platform for the analysis of disease outbreaks.",2014 Jun,"['Jombart, Thibaut', 'Aanensen, David M.', 'Baguelin, Marc', 'Birrell, Paul', 'Cauchemez, Simon', 'Camacho, Anton', 'Colijn, Caroline', 'Collins, Caitlin', 'Cori, Anne', 'Didelot, Xavier', 'Fraser, Christophe', 'Frost, Simon', 'Hens, Niel', 'Hugues, Joseph', 'Höhle, Michael', 'Opatowski, Lulla', 'Rambaut, Andrew', 'Ratmann, Oliver', 'Soubeyrand, Samuel', 'Suchard, Marc A.', 'Wallinga, Jacco', 'Ypma, Rolf', 'Ferguson, Neil']",Epidemics,,,
,PMC,Human Vaccines & Immunotherapeutics:  News,http://dx.doi.org/10.4161/hv.32075,PMC5396245,,,"Sanofi Pasteur shows efficacy of its dengue vaccine in phase 3 New glioblastoma vaccine: Safe and immunogenic in phase 1 FDA approves sublingual hay fever immunotherapeutic Combining the cancer vaccine DPX-Survivac with immune modulators Two Meningococcal B vaccines receive FDA ‚Breakthrough Therapy’ designation MERS vaccine is technically feasible, but is it commerically feasible? Stemline’s synthetic multi-peptide cancer vaccine enters Phase 2 Evolution of whooping cough bacterium may reduce vaccine effectiveness",,"Riedmann, Eva M",,,,
,PMC,Viral Phosphodiesterases That Antagonize Double-Stranded RNA Signaling to RNase L by Degrading 2-5A,http://dx.doi.org/10.1089/jir.2014.0007,PMC4046343,,,"The host interferon (IFN) antiviral response involves a myriad of diverse biochemical pathways that disrupt virus replication cycles at many different levels. As a result, viruses have acquired and evolved genes that antagonize the host antiviral proteins. IFNs inhibit viral infections in part through the 2′,5′-oligoadenylate (2-5A) synthetase (OAS)/RNase L pathway. OAS proteins are pathogen recognition receptors that exist at different basal levels in different cell types and that are IFN inducible. Upon activation by the pathogen-associated molecular pattern viral double-stranded RNA, certain OAS proteins synthesize 2-5A from ATP. 2-5A binds to the antiviral enzyme RNase L causing its dimerization and activation. Recently, disparate RNA viruses, group 2a betacoronaviruses, and group A rotaviruses, have been shown to produce proteins with 2′,5′-phosphodiesterase (PDE) activities that eliminate 2-5A thereby evading the antiviral activity of the OAS/RNase L pathway. These viral proteins are members of the eukaryotic-viral LigT-like group of 2H phosphoesterases, so named for the presence of 2 conserved catalytic histidine residues. Here, we will review the biochemistry, biology, and implications of viral and cellular 2′,5′-PDEs that degrade 2-5A. In addition, we discuss alternative viral and cellular strategies for limiting the activity of OAS/RNase L.",,"['Silverman, Robert H.', 'Weiss, Susan R.']",,,,
,PMC,Primary ciliary dyskinesia: From diagnosis to molecular mechanisms,http://dx.doi.org/10.3233/PGE-14088,PMC5020995,,,"Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder affecting motile cilia. This can lead to neonatal respiratory distress, early onset upper and lower airway infections, laterality abnormalities and sub- or infertility. Although disease progression shows large individual variability, all adult patients eventually develop extensive bronchiectasis. As in cystic fibrosis, early diagnosis and frequent follow-up with microbiological control is the best therapeutic strategy, as other treatment options are lacking. PCD is underdiagnosed and diagnosed late due to clinical unawareness, limited availability of diagnostic tests and difficult interpretation of test results. Diagnosis is currently based on a combination of assessment of ciliary motion and ultrastructure by high-speed video microscopy and electron microscopy, respectively. As nasal nitric oxide is low in almost all PCD patients, these measurements can be used for screening. Although there are 26 PCD genes known so far, the genetic basis of the disease has not been unraveled in an estimated 30–40% of patients. However, the rapid discovery of novel PCD genes in recent years is expected to enable accurate genetic characterization of most patients in the near future. Large-scale use of next-generation sequencing and the availability of large ciliary proteomic and transcriptomic databases accelerate the identification of novel PCD genes, especially those that play a key role in cytoplasmic assembly of ciliary ultrastructural components. These genetic advances are revolutionizing the process of obtaining a molecular diagnosis for PCD as we speak and may ultimately lead to an increased understanding of ciliogenesis and function, providing novel handles for therapeutic interventions in PCD patients.",,"['Paff, Tamara', 'Daniels, Johannes M.A.', 'Pals, Gerard', 'Haarman, Eric G.']",,,,
,PMC,Protein Interferon-Stimulated Gene 15 Conjugation Delays but Does Not Overcome Coronavirus Proliferation in a Model of Fulminant Hepatitis,http://dx.doi.org/10.1128/JVI.03801-13,PMC4093886,,,"Coronaviruses express a deubiquitinating protein, the papain-like protease-2 (PLP2), that removes both ubiquitin and the ubiquitin-like interferon (IFN)-stimulated gene 15 (ISG15) protein from target proteins. ISG15 has antiviral activity against a number of viruses; therefore, we examined the effect of ISG15 conjugation (ISGylation) in a model of acute viral hepatitis induced by the murine hepatitis virus strain 3 (MHV-3) coronavirus. Mice deficient in the ISG15 deconjugating enzyme, ubiquitin-specific peptidase-18 (USP18), accumulate high levels of ISG15-conjugated proteins and are hypersensitive to type I IFN. Infecting USP18(−/−) mice with MHV-3 resulted in extended survival (8 ± 1.2 versus 4 days) and in improved liver histology, a decreased inflammatory response, and viral titers 1 to 2 logs lower than in USP18(+/+) mice. The suppression of viral replication was not due to increased IFN since infected USP18(−/−) mice had neither increased hepatic IFN-α, -β, or -γ mRNA nor circulating protein. Instead, delayed MHV-3 replication coincided with high levels of cellular ISGylation. Decreasing ISGylation by knockdown of the ISG15 E1 enzyme, Ube1L, in primary USP18(+/+) and USP18(−/−) hepatocytes led to increased MHV-3 replication. Both in vitro and in vivo, increasing MHV-3 titers were coincident with increased PLP2 mRNA and decreased ISGylation over the course of infection. The pharmacologic inhibition of the PLP2 enzyme in vitro led to decreased MHV-3 replication. Overall, these results demonstrate the antiviral effect of ISGylation in an in vivo model of coronavirus-induced mouse hepatitis and illustrate that PLP2 manipulates the host innate immune response through the ISG15/USP18 pathway. IMPORTANCE There have been a number of serious worldwide pandemics due to widespread infections by coronavirus. This virus (in its many forms) is difficult to treat, in part because it is very good at finding “holes” in the way that the host (the infected individual) tries to control and eliminate the virus. In this study, we demonstrate that an important host viral defense—the ISG15 pathway—is only partially effective in controlling severe coronavirus infection. Activation of the pathway is very good at suppressing viral production, but over time the virus overwhelms the host response and the effects of the ISG15 pathway. These data provide insight into host-virus interactions during coronavirus infection and suggest that the ISG15 pathway is a reasonable target for controlling severe coronavirus infection although the best treatment will likely involve multiple pathways and targets.",,"['Ma, Xue-Zhong', 'Bartczak, Agata', 'Zhang, Jianhua', 'He, Wei', 'Shalev, Itay', 'Smil, David', 'Chen, Limin', 'Phillips, Jim', 'Feld, Jordan J.', 'Selzner, Nazia', 'Levy, Gary', 'McGilvray, Ian']",,,,
,PMC,Animal Model of Respiratory Syncytial Virus: CD8(+) T Cells Cause a Cytokine Storm That Is Chemically Tractable by Sphingosine-1-Phosphate 1 Receptor Agonist Therapy,http://dx.doi.org/10.1128/JVI.00464-14,PMC4093868,,,"The cytokine storm is an intensified, dysregulated, tissue-injurious inflammatory response driven by cytokine and immune cell components. The cytokine storm during influenza virus infection, whereby the amplified innate immune response is primarily responsible for pulmonary damage, has been well characterized. Now we describe a novel event where virus-specific T cells induce a cytokine storm. The paramyxovirus pneumonia virus of mice (PVM) is a model of human respiratory syncytial virus (hRSV). Unexpectedly, when C57BL/6 mice were infected with PVM, the innate inflammatory response was undetectable until day 5 postinfection, at which time CD8(+) T cells infiltrated into the lung, initiating a cytokine storm by their production of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Administration of an immunomodulatory sphingosine-1-phosphate (S1P) receptor 1 (S1P1R) agonist significantly inhibited PVM-elicited cytokine storm by blunting the PVM-specific CD8(+) T cell response, resulting in diminished pulmonary disease and enhanced survival. IMPORTANCE A dysregulated overly exuberant immune response, termed a “cytokine storm,” accompanies virus-induced acute respiratory diseases (VARV), is primarily responsible for the accompanying high morbidity and mortality, and can be controlled therapeutically in influenza virus infection of mice and ferrets by administration of sphingosine-1-phosphate 1 receptor (S1P1R) agonists. Here, two novel findings are recorded. First, in contrast to influenza infection, where the cytokine storm is initiated early by the innate immune system, for pneumonia virus of mice (PVM), a model of RSV, the cytokine storm is initiated late in infection by the adaptive immune response: specifically, by virus-specific CD8 T cells via their release of IFN-γ and TNF-α. Blockading these cytokines with neutralizing antibodies blunts the cytokine storm and protects the host. Second, PVM infection is controlled by administration of an S1P1R agonist.",,"['Walsh, Kevin B.', 'Teijaro, John R.', 'Brock, Linda G.', 'Fremgen, Daniel M.', 'Collins, Peter L.', 'Rosen, Hugh', 'Oldstone, Michael B. A.']",,,,
,PMC,Efficient Reovirus- and Measles Virus-Mediated Pore Expansion during Syncytium Formation Is Dependent on Annexin A1 and Intracellular Calcium,http://dx.doi.org/10.1128/JVI.00121-14,PMC4093853,,,"Orthoreovirus fusion-associated small transmembrane (FAST) proteins are dedicated cell-cell fusogens responsible for multinucleated syncytium formation and are virulence determinants of the fusogenic reoviruses. While numerous studies on the FAST proteins and enveloped-virus fusogens have delineated steps involved in membrane fusion and pore formation, little is known about the mechanics of pore expansion needed for syncytiogenesis. We now report that RNA interference (RNAi) knockdown of annexin A1 (AX1) expression dramatically reduced both reptilian reovirus p14 and measles virus F and H protein-mediated pore expansion during syncytiogenesis but had no effect on pore formation. A similar effect was obtained by chelating intracellular calcium, which dramatically decreased syncytiogenesis in the absence of detectable effects on p14-induced pore formation. Coimmunoprecipitation revealed calcium-dependent interaction between AX1 and p14 or measles virus F and H proteins, and fluorescence resonance energy transfer (FRET) demonstrated calcium-dependent p14-AX1 interactions in cellulo. Furthermore, antibody inhibition of extracellular AX1 had no effect on p14-induced syncytium formation but did impair cell-cell fusion mediated by the endogenous muscle cell fusion machinery in C2C12 mouse myoblasts. AX1 can therefore exert diverse, fusogen-specific effects on cell-cell fusion, functioning as an extracellular mediator of differentiation-dependent membrane fusion or as an intracellular promoter of postfusion pore expansion and syncytium formation following virus-mediated cell-cell fusion. IMPORTANCE Numerous enveloped viruses and nonenveloped fusogenic orthoreoviruses encode membrane fusion proteins that induce syncytium formation, which has been linked to viral pathogenicity. Considerable insights into the mechanisms of membrane fusion have been obtained, but processes that drive postfusion expansion of fusion pores to generate syncytia are poorly understood. This study identifies intracellular calcium and annexin A1 (AX1) as key factors required for efficient pore expansion during syncytium formation mediated by the reptilian reovirus p14 and measles virus F and H fusion protein complexes. Involvement of intracellular AX1 in syncytiogenesis directly correlates with a requirement for intracellular calcium in p14-AX1 interactions and pore expansion but not membrane fusion and pore formation. This is the first demonstration that intracellular AX1 is involved in pore expansion, which suggests that the AX1 pathway may be a common host cell response needed to resolve virus-induced cell-cell fusion pores.",,"['Ciechonska, Marta', 'Key, Tim', 'Duncan, Roy']",,,,
,PMC,Reinitiation after Translation of Two Upstream Open Reading Frames (ORF) Governs Expression of the ORF35-37 Kaposi's Sarcoma-Associated Herpesvirus Polycistronic mRNA,http://dx.doi.org/10.1128/JVI.00202-14,PMC4093840,,,"The Kaposi's sarcoma-associated herpesvirus (KSHV) ORF36 protein kinase is translated as a downstream gene from the ORF35-37 polycistronic mRNA via a unique mechanism involving short upstream open reading frames (uORFs) located in the 5′ untranslated region. Here, we confirm that ORF35-37 is functionally dicistronic during infection and demonstrate that mutation of the dominant uORF restricts KSHV replication. Leaky scanning past the uORFs facilitates ORF35 expression, while a reinitiation mechanism after translation of the uORFs enables ORF36 expression.",,"['Kronstad, Lisa M.', 'Brulois, Kevin F.', 'Jung, Jae U.', 'Glaunsinger, Britt A.']",,,,
,PMC,Neurovirulence and Immunogenicity of Attenuated Recombinant Vesicular Stomatitis Viruses in Nonhuman Primates,http://dx.doi.org/10.1128/JVI.03441-13,PMC4054374,,,"In previous work, a prototypic recombinant vesicular stomatitis virus Indiana serotype (rVSIV) vector expressing simian immunodeficiency virus (SIV) gag and human immunodeficiency virus type 1 (HIV-1) env antigens protected nonhuman primates (NHPs) from disease following challenge with an HIV-1/SIV recombinant (SHIV). However, when tested in a stringent NHP neurovirulence (NV) model, this vector was not adequately attenuated for clinical evaluation. For the work described here, the prototypic rVSIV vector was attenuated by combining specific G protein truncations with either N gene translocations or mutations (M33A and M51A) that ablate expression of subgenic M polypeptides, by incorporation of temperature-sensitive mutations in the N and L genes, and by deletion of the VSIV G gene to generate a replicon that is dependent on trans expression of G protein for in vitro propagation. When evaluated in a series of NHP NV studies, these attenuated rVSIV variants caused no clinical disease and demonstrated a very significant reduction in neuropathology compared to wild-type VSIV and the prototypic rVSIV vaccine vector. In spite of greatly increased in vivo attenuation, some of the rVSIV vectors elicited cell-mediated immune responses that were similar in magnitude to those induced by the much more virulent prototypic vector. These data demonstrate novel approaches to the rational attenuation of VSIV NV while retaining vector immunogenicity and have led to identification of an rVSIV N4CT1gag1 vaccine vector that has now successfully completed phase I clinical evaluation. IMPORTANCE The work described in this article demonstrates a rational approach to the attenuation of vesicular stomatitis virus neurovirulence. The major attenuation strategy described here will be most likely applicable to other members of the Rhabdoviridae and possibly other families of nonsegmented negative-strand RNA viruses. These studies have also enabled the identification of an attenuated, replication-competent rVSIV vector that has successfully undergone its first clinical evaluation in humans. Therefore, these studies represent a major milestone in the development of attenuated rVSIV, and likely other vesiculoviruses, as a new vaccine platform(s) for use in humans.",,"['Clarke, David K.', 'Nasar, Farooq', 'Chong, Siew', 'Johnson, J. Erik', 'Coleman, John W.', 'Lee, Margaret', 'Witko, Susan E.', 'Kotash, Cheryl S.', 'Abdullah, Rashed', 'Megati, Shakuntala', 'Luckay, Amara', 'Nowak, Becky', 'Lackner, Andrew', 'Price, Roger E.', 'Little, Peter', 'Kalyan, Narender', 'Randolf, Valerie', 'Javadian, Ali', 'Zamb, Timothy J.', 'Parks, Christopher L.', 'Egan, Michael A.', 'Eldridge, John', 'Hendry, Michael', 'Udem, Stephen A.']",,,,
,PMC,A Conformation-Dependent Neutralizing Monoclonal Antibody Specifically Targeting Receptor-Binding Domain in Middle East Respiratory Syndrome Coronavirus Spike Protein,http://dx.doi.org/10.1128/JVI.00433-14,PMC4054355,,,"Prophylactic and therapeutic strategies are urgently needed to combat infections caused by the newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have developed a neutralizing monoclonal antibody (MAb), designated Mersmab1, which potently blocks MERS-CoV entry into human cells. Biochemical assays reveal that Mersmab1 specifically binds to the receptor-binding domain (RBD) of the MERS-CoV spike protein and thereby competitively blocks the binding of the RBD to its cellular receptor, dipeptidyl peptidase 4 (DPP4). Furthermore, alanine scanning of the RBD has identified several residues at the DPP4-binding surface that serve as neutralizing epitopes for Mersmab1. These results suggest that if humanized, Mersmab1 could potentially function as a therapeutic antibody for treating and preventing MERS-CoV infections. Additionally, Mersmab1 may facilitate studies of the conformation and antigenicity of MERS-CoV RBD and thus will guide rational design of MERS-CoV subunit vaccines. IMPORTANCE MERS-CoV is spreading in the human population and causing severe respiratory diseases with over 40% fatality. No vaccine is currently available to prevent MERS-CoV infections. Here, we have produced a neutralizing monoclonal antibody with the capacity to effectively block MERS-CoV entry into permissive human cells. If humanized, this antibody may be used as a prophylactic and therapeutic agent against MERS-CoV infections. Specifically, when given to a person (e.g., a patient's family member or a health care worker) either before or after exposure to MERS-CoV, the humanized antibody may prevent or inhibit MERS-CoV infection, thereby stopping the spread of MERS-CoV in humans. This antibody can also serve as a useful tool to guide the design of effective MERS-CoV vaccines.",,"['Du, Lanying', 'Zhao, Guangyu', 'Yang, Yang', 'Qiu, Hongjie', 'Wang, Lili', 'Kou, Zhihua', 'Tao, Xinrong', 'Yu, Hong', 'Sun, Shihui', 'Tseng, Chien-Te K.', 'Jiang, Shibo', 'Li, Fang', 'Zhou, Yusen']",,,,
,PMC,Identification of Diverse Alphacoronaviruses and Genomic Characterization of a Novel Severe Acute Respiratory Syndrome-Like Coronavirus from Bats in China,http://dx.doi.org/10.1128/JVI.00631-14,PMC4054348,,,"Although many severe acute respiratory syndrome-like coronaviruses (SARS-like CoVs) have been identified in bats in China, Europe, and Africa, most have a genetic organization significantly distinct from human/civet SARS CoVs in the receptor-binding domain (RBD), which mediates receptor binding and determines the host spectrum, resulting in their failure to cause human infections and making them unlikely progenitors of human/civet SARS CoVs. Here, a viral metagenomic analysis of 268 bat rectal swabs collected from four counties in Yunnan Province has identified hundreds of sequences relating to alpha- and betacoronaviruses. Phylogenetic analysis based on a conserved region of the RNA-dependent RNA polymerase gene revealed that alphacoronaviruses had diversities with some obvious differences from those reported previously. Full genomic analysis of a new SARS-like CoV from Baoshan (LYRa11) showed that it was 29,805 nucleotides (nt) in length with 13 open reading frames (ORFs), sharing 91% nucleotide identity with human/civet SARS CoVs and the most recently reported SARS-like CoV Rs3367, while sharing 89% with other bat SARS-like CoVs. Notably, it showed the highest sequence identity with the S gene of SARS CoVs and Rs3367, especially in the RBD region. Antigenic analysis showed that the S1 domain of LYRa11 could be efficiently recognized by SARS-convalescent human serum, indicating that LYRa11 is a novel virus antigenically close to SARS CoV. Recombination analyses indicate that LYRa11 is likely a recombinant descended from parental lineages that had evolved into a number of bat SARS-like CoVs. IMPORTANCE Although many severe acute respiratory syndrome-like coronaviruses (SARS-like CoVs) have been discovered in bats worldwide, there are significant different genic structures, particularly in the S1 domain, which are responsible for host tropism determination, between bat SARS-like CoVs and human SARS CoVs, indicating that most reported bat SARS-like CoVs are not the progenitors of human SARS CoV. We have identified diverse alphacoronaviruses and a close relative (LYRa11) to SARS CoV in bats collected in Yunnan, China. Further analysis showed that alpha- and betacoronaviruses have different circulation and transmission dynamics in bat populations. Notably, full genomic sequencing and antigenic study demonstrated that LYRa11 is phylogenetically and antigenically closely related to SARS CoV. Recombination analyses indicate that LYRa11 is a recombinant from certain bat SARS-like CoVs circulating in Yunnan Province.",,"['He, Biao', 'Zhang, Yuzhen', 'Xu, Lin', 'Yang, Weihong', 'Yang, Fanli', 'Feng, Yun', 'Xia, Lele', 'Zhou, Jihua', 'Zhen, Weibin', 'Feng, Ye', 'Guo, Huancheng', 'Zhang, Hailin', 'Tu, Changchun']",,,,
,PMC,Expression of Recombinant Vaccines and Antibodies in Plants,http://dx.doi.org/10.1089/mab.2014.0049,PMC4063376,,,"Plants are able to perform post-translational maturations of therapeutic proteins required for their functional biological activity and suitable in vivo pharmacokinetics. Plants can be a low-cost, large-scale production platform of recombinant biopharmaceutical proteins such as vaccines and antibodies. Plants, however, lack mechanisms of processing authentic human N-glycosylation, which imposes a major limitation in their use as an expression system for therapeutic glycoproducts. Efforts have been made to circumvent plant-specific N-glycosylation, as well as to supplement the plant's endogenous system with human glycosyltransferases for non-immunogenic and humanized N-glycan production. Herein we review studies on the potential of plants to serve as production systems for therapeutic and prophylactic biopharmaceuticals. We have especially focused on recombinant vaccines and antibodies and new expression strategies to overcome the existing problems associated with their production in plants.",,"Ko, Kisung",,,,
,PMC,Neuroinfectious disease: A rapidly evolving challenge,http://dx.doi.org/10.1212/CPJ.0000000000000024,PMC5764512,,,,,"Clifford, David B.",,,,
,PMC,Debate on MERS-CoV respiratory precautions: surgical mask or N95 respirators?,http://dx.doi.org/10.11622/smedj.2014076,PMC4294054,,,"Since the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in mid-2012, there has been controversy over the respiratory precaution recommendations in different guidelines from various international bodies. Our understanding of MERS-CoV is still evolving. Current recommendations on infection control practices are heavily influenced by the lessons learnt from severe acute respiratory syndrome. A debate on respiratory precautions for MERS-CoV was organised by Infection Control Association (Singapore) and the Society of Infectious Disease (Singapore). We herein discuss and present the evidence for surgical masks for the protection of healthcare workers from MERS-CoV.",,"['Chung, Jasmine Shimin', 'Ling, Moi Lin', 'Seto, Wing Hong', 'Ang, Brenda Sze Peng', 'Tambyah, Paul Anantharajah']",,,,
,PMC,Respiratory precautions for MERS-CoV: acceptable risk-benefit determination,http://dx.doi.org/10.11622/smedj.2014075,PMC4294053,,,,,"Hsu, Li Yang",,,,
,PMC,Structures of PI4KIIIβ complexes show simultaneous recruitment of Rab11 and its effectors,http://dx.doi.org/10.1126/science.1253397,PMC4046302,,,"Phosphatidylinositol 4-kinases (PI4Ks) and small guanosine triphosphatases (GTPases) are essential for processes that require expansion and remodeling of phosphatidylinositol 4-phosphate (PI4P)-containing membranes, including cytokinesis, intracellular development of malarial pathogens, and replication of a wide range of RNA viruses. However, the structural basis for coordination of PI4K, GTPases and their effectors is unknown. Here, we describe structures of PI4KB (PI4KIIIβ) bound to the small GTPase Rab11a without and with the Rab11 effector protein FIP3. The Rab11-PI4KIIIβ interface is unique compared with known structures of Rab complexes, and does not involve switch regions used by GTPase effectors. Our data provide a mechanism for how PI4KIIIβ coordinates Rab11 and its effectors on PI4P-enriched membranes, and also provide strategies for the design of specific inhibitors that could potentially target plasmodial PI4KIIIβ to combat malaria.",,"['Burke, John E.', 'Inglis, Alison J.', 'Perisic, Olga', 'Masson, Glenn R.', 'McLaughlin, Stephen H.', 'Rutaganira, Florentine', 'Shokat, Kevan M.', 'Williams, Roger L.']",,,,
,PMC,Influenza entry pathways in polarized MDCK cells,http://dx.doi.org/10.1016/j.bbrc.2014.05.095,PMC4107043,,,"In non-polarized cell culture models, influenza virus has been shown to enter host cells via multiple endocytic pathways, including classical clathrin-mediated endocytic routes (CME), clathrin- and caveolae-independent routes and macropinocytosis. However, little is known about the entry route of influenza virus in differentiated epithelia, in vivo site of infection for influenza virus. Here, we show that in polarized Madin-Darby canine kidney type II (MDCK II) cells, influenza virus has a specific utilization of the clathrin-mediated endocytic pathway and requires Eps15 for host cell entry.",,"['Zhang, Yueting', 'Whittaker, Gary R.']",,,,
,PMC,Plasmacytoid Dendritic Cell-Derived IFN-α Promotes Murine Liver Ischemia/Reperfusion Injury Via Induction of Hepatocyte IRF-1,http://dx.doi.org/10.1002/hep.27037,PMC4077928,,,"Plasmacytoid dendritic cells (pDC) constitute the body’s principal source of type I interferon (IFN) and are comparatively abundant in the liver. Among various cytokines implicated in liver ischemia and reperfusion (I/R) injury, type I IFNs have been described recently as playing an essential role in its pathogenesis. Moreover, type I IFNs have been shown to up-regulate hepatocyte expression of IFN regulatory factor 1 (IRF-1), a key transcription factor that regulates apoptosis and induces liver damage after I/R. Our aim was to ascertain the capacity of IFN-α released by liver pDC to induce liver damage through hepatic IRF-1 up-regulation after I/R injury. Our findings show that liver pDC mature and produce IFN-α in response to liver I/R. Liver pDC isolated after I/R induced elevated levels of IRF-1 production by hepatocytes compared with liver pDC isolated from sham-operated mice. Notably, hepatic IRF-1 expression was reduced significantly by neutralizing IFN-α. In vivo, IFN-α neutralization protected the liver from I/R injury by reducing hepatocyte apoptosis. This was associated with impaired expression of IRF-1 and pro-apoptotic molecules such as Fas ligand, its receptor (Fas) and death receptor 5 which are regulated by IRF-1. Furthermore, pDC-depleted mice failed to up-regulate hepatic IFN-α and displayed less liver injury associated with reduced levels of hepatic IL-6, tumor necrosis factor-α and hepatocyte apoptosis after I/R compared with controls. Conclusion: these data support the hypothesis that IFN-α derived from liver pDC plays a key role in the pathogenesis of liver I/R injury by enhancing apoptosis as a consequence of induction of hepatocyte IRF-1 expression.",,"['Castellaneta, Antonino', 'Yoshida, Osamu', 'Kimura, Shoko', 'Yokota, Shinichiro', 'Geller, David A.', 'Murase, Noriko', 'Thomson, Angus W.']",,,,
,PMC,Wanderings in Biochemistry,http://dx.doi.org/10.1074/jbc.X114.554121,PMC4094036,,,"My Ph.D. thesis in the laboratory of Severo Ochoa at New York University School of Medicine in 1962 included the determination of the nucleotide compositions of codons specifying amino acids. The experiments were based on the use of random copolyribonucleotides (synthesized by polynucleotide phosphorylase) as messenger RNA in a cell-free protein-synthesizing system. At Yale University, where I joined the faculty, my co-workers and I first studied the mechanisms of protein synthesis. Thereafter, we explored the interferons (IFNs), which were discovered as antiviral defense agents but were revealed to be components of a highly complex multifunctional system. We isolated pure IFNs and characterized IFN-activated genes, the proteins they encode, and their functions. We concentrated on a cluster of IFN-activated genes, the p200 cluster, which arose by repeated gene duplications and which encodes a large family of highly multifunctional proteins. For example, the murine protein p204 can be activated in numerous tissues by distinct transcription factors. It modulates cell proliferation and the differentiation of a variety of tissues by binding to many proteins. p204 also inhibits the activities of wild-type Ras proteins and Ras oncoproteins.",,"Lengyel, Peter",,,,
,PMC,Phylogenetic evidence for a mild H1 pandemic in the early 1900s,http://dx.doi.org/10.1073/pnas.1406869111,PMC4050630,,,,,"Riley, Steven",,,,
,PMC,Quantitative Proteomic Analysis of Host-virus Interactions Reveals a Role for Golgi Brefeldin A Resistance Factor 1 (GBF1) in Dengue Infection,http://dx.doi.org/10.1074/mcp.M114.038984,PMC4223476,,,"Dengue virus is considered to be the most important mosquito-borne virus worldwide and poses formidable economic and health care burdens on many tropical and subtropical countries. Dengue infection induces drastic rearrangement of host endoplasmic reticulum membranes into complex membranous structures housing replication complexes; the contribution(s) of host proteins and pathways to this process is poorly understood but is likely to be mediated by protein-protein interactions. We have developed an approach for obtaining high confidence protein-protein interaction data by employing affinity tags and quantitative proteomics, in the context of viral infection, followed by robust statistical analysis. Using this approach, we identified high confidence interactors of NS5, the viral polymerase, and NS3, the helicase/protease. Quantitative proteomics allowed us to exclude a large number of presumably nonspecific interactors from our data sets and imparted a high level of confidence to our resulting data sets. We identified 53 host proteins reproducibly associated with NS5 and 41 with NS3, with 13 of these candidates present in both data sets. The host factors identified have diverse functions, including retrograde Golgi-to-endoplasmic reticulum transport, biosynthesis of long-chain fatty-acyl-coenzyme As, and in the unfolded protein response. We selected GBF1, a guanine nucleotide exchange factor responsible for ARF activation, from the NS5 data set for follow up and functional validation. We show that GBF1 plays a critical role early in dengue infection that is independent of its role in the maintenance of Golgi structure. Importantly, the approach described here can be applied to virtually any organism/system as a tool for better understanding its molecular interactions.",,"['Carpp, Lindsay N.', 'Rogers, Richard S.', 'Moritz, Robert L.', 'Aitchison, John D.']",,,,
,PMC,Analysis of synonymous codon usage in enterovirus 71,http://dx.doi.org/10.1007/s13337-014-0215-y,PMC4188181,,,"Enterovirus 71 (EV71) is the major cause of hand-foot-and-mouth disease in children. In our study, using the complete genome sequences of 42 EV71 representing all three genotypes, we analyzed synonymous codon usage and the relative dinucleotide abundance in EV71 genome. The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in EV71 genome. Furthermore, we observed that the relative abundance of dinucleotides in EV71 is independent of the overall base composition but is still the result of differential mutational pressure, which also shapes codon usage. In addition, other factors, such as hydrophobicity and aromaticity, also influence the codon usage variation among the genomes of EV71. This study represents the most comprehensive analysis of EV71 codon usage patterns and provides a basic understanding of the mechanisms for codon usage bias.",,"['Zhang, Hua', 'Cao, Hong-wei', 'Li, Feng-qi', 'Pan, Zi-ye', 'Wu, Zhi-jun', 'Wang, Yan-hong', 'Cui, Yu-dong']",,,,
,PMC,Systems analysis of West Nile virus infection,http://dx.doi.org/10.1016/j.coviro.2014.04.010,PMC4104408,,,"Emerging and re-emerging mosquito-borne viruses continue to pose a significant threat to human health throughout the world. Over the past decade, West Nile virus (WNV), Dengue virus (DENV), and Chikungunya virus (CHIKV), have caused annual epidemics of virus-induced encephalitis, hemorrhagic fever\shock syndromes, and arthritis, respectively. Currently, no specific antiviral therapies or vaccines exist for use in humans to combat or prevent these viral infections. Thus, there is a pressing need to define the virus-host interactions that govern immunity and infection outcome. Recent technological breakthroughs in ‘omics’ resources and high-throughput based assays are beginning to accelerate antiviral drug discovery and improve on current strategies for vaccine design. In this review, we highlight studies with WNV and discuss how traditional and systems based approaches are being used to rapidly identify novel host targets for therapeutic intervention and develop a deeper conceptual understanding of the host response to virus infection.",,"['Suthar, Mehul S.', 'Pulendran, Bali']",,,,
,PMC,"Time-varying, serotype-specific force of infection of dengue virus",http://dx.doi.org/10.1073/pnas.1314933111,PMC4084484,,,"Infectious disease models play a key role in public health planning. These models rely on accurate estimates of key transmission parameters such as the force of infection (FoI), which is the per-capita risk of a susceptible person being infected. The FoI captures the fundamental dynamics of transmission and is crucial for gauging control efforts, such as identifying vaccination targets. Dengue virus (DENV) is a mosquito-borne, multiserotype pathogen that currently infects ∼390 million people a year. Existing estimates of the DENV FoI are inaccurate because they rely on the unrealistic assumption that risk is constant over time. Dengue models are thus unreliable for designing vaccine deployment strategies. Here, we present to our knowledge the first time-varying (daily), serotype-specific estimates of DENV FoIs using a spline-based fitting procedure designed to examine a 12-y, longitudinal DENV serological dataset from Iquitos, Peru (11,703 individuals, 38,416 samples, and 22,301 serotype-specific DENV infections from 1999 to 2010). The yearly DENV FoI varied markedly across time and serotypes (0–0.33), as did daily basic reproductive numbers (0.49–4.72). During specific time periods, the FoI fluctuations correlated across serotypes, indicating that different DENV serotypes shared common transmission drivers. The marked variation in transmission intensity that we detected indicates that intervention targets based on one-time estimates of the FoI could underestimate the level of effort needed to prevent disease. Our description of dengue virus transmission dynamics is unprecedented in detail, providing a basis for understanding the persistence of this rapidly emerging pathogen and improving disease prevention programs.",,"['Reiner, Robert C.', 'Stoddard, Steven T.', 'Forshey, Brett M.', 'King, Aaron A.', 'Ellis, Alicia M.', 'Lloyd, Alun L.', 'Long, Kanya C.', 'Rocha, Claudio', 'Vilcarromero, Stalin', 'Astete, Helvio', 'Bazan, Isabel', 'Lenhart, Audrey', 'Vazquez-Prokopec, Gonzalo M.', 'Paz-Soldan, Valerie A.', 'McCall, Philip J.', 'Kitron, Uriel', 'Elder, John P.', 'Halsey, Eric S.', 'Morrison, Amy C.', 'Kochel, Tadeusz J.', 'Scott, Thomas W.']",,,,
,PMC,Implementing hospital-based surveillance for severe acute respiratory infections caused by influenza and other respiratory pathogens in New Zealand,http://dx.doi.org/10.5365/WPSAR.2014.5.1.004,PMC4113656,,,"BACKGROUND: Recent experience with pandemic influenza A(H1N1)pdm09 highlighted the importance of global surveillance for severe respiratory disease to support pandemic preparedness and seasonal influenza control. Improved surveillance in the southern hemisphere is needed to provide critical data on influenza epidemiology, disease burden, circulating strains and effectiveness of influenza prevention and control measures. Hospital-based surveillance for severe acute respiratory infection (SARI) cases was established in New Zealand on 30 April 2012. The aims were to measure incidence, prevalence, risk factors, clinical spectrum and outcomes for SARI and associated influenza and other respiratory pathogen cases as well as to understand influenza contribution to patients not meeting SARI case definition. METHODS/DESIGN: All inpatients with suspected respiratory infections who were admitted overnight to the study hospitals were screened daily. If a patient met the World Health Organization’s SARI case definition, a respiratory specimen was tested for influenza and other respiratory pathogens. A case report form captured demographics, history of presenting illness, co-morbidities, disease course and outcome and risk factors. These data were supplemented from electronic clinical records and other linked data sources. DISCUSSION: Hospital-based SARI surveillance has been implemented and is fully functioning in New Zealand. Active, prospective, continuous, hospital-based SARI surveillance is useful in supporting pandemic preparedness for emerging influenza A(H7N9) virus infections and seasonal influenza prevention and control.",,"['Huang, Q Sue', 'Baker, Michael', 'McArthur, Colin', 'Roberts, Sally', 'Williamson, Deborah', 'Grant, Cameron', 'Trenholme, Adrian', 'Wong, Conroy', 'Taylor, Susan', 'LeComte, Lyndsay', 'Mackereth, Graham', 'Bandaranayake, Don', 'Wood, Tim', 'Bissielo, Ange', 'Se, Ruth', 'Turner, Nikki', 'Pierse, Nevil', 'Thomas, Paul', 'Webby, Richard', 'Gross, Diane', 'Duque, Jazmin', 'Thompson, Mark', 'Widdowson, Marc-Alain']",,,,
,PMC,Two-photon imaging of remyelination of spinal cord axons by engrafted neural precursor cells in a viral model of multiple sclerosis,http://dx.doi.org/10.1073/pnas.1406658111,PMC4050611,,,"Neural precursor cells (NPCs) offer a promising approach for treating demyelinating diseases. However, the cellular dynamics that underlie transplanted NPC-mediated remyelination have not been described. Using two-photon imaging of a newly developed ventral spinal cord preparation and a viral model of demyelination, we describe the motility and intercellular interactions of transplanted mouse NPCs expressing green fluorescent protein (GFP) with damaged axons expressing yellow fluorescent protein (YFP). Our findings reveal focal axonal degeneration that occurs in the ventral side of the spinal cord within 1 wk following intracranial instillation with the neurotropic JHM strain of mouse hepatitis virus (JHMV). Axonal damage precedes extensive demyelination and is characterized by swelling along the length of the axon, loss of YFP signal, and transected appearance. NPCs engrafted into spinal cords of JHMV-infected mice exhibited diminished migration velocities and increased proliferation compared with transplanted cells in noninfected mice. NPCs preferentially accumulated within areas of axonal damage, initiated direct contact with axons, and subsequently expressed the myelin proteolipid protein gene, initiating remyelination. These findings indicate that NPCs transplanted into an inflammatory demyelinating microenvironment participate directly in therapeutic outcome through the wrapping of myelin around damaged neurons.",,"['Greenberg, Milton L.', 'Weinger, Jason G.', 'Matheu, Melanie P.', 'Carbajal, Kevin S.', 'Parker, Ian', 'Macklin, Wendy B.', 'Lane, Thomas E.', 'Cahalan, Michael D.']",,,,
,PMC,Systems approaches to coronavirus pathogenesis,http://dx.doi.org/10.1016/j.coviro.2014.04.007,PMC4076299,,,"Coronaviruses comprise a large group of emergent human and animal pathogens, including the highly pathogenic SARS-CoV and MERS-CoV strains that cause significant morbidity and mortality in infected individuals, especially the elderly. As emergent viruses may cause episodic outbreaks of disease over time, human samples are limited. Systems biology and genetic technologies maximize opportunities for identifying critical host and viral genetic factors that regulate susceptibility and virus-induced disease severity. These approaches provide discovery platforms that highlight and allow targeted confirmation of critical targets for prophylactics and therapeutics, especially critical in an outbreak setting. Although poorly understood, it has long been recognized that host regulation of virus-associated disease severity is multigenic. The advent of systems genetic and biology resources provide new opportunities for deconvoluting the complex genetic interactions and expression networks that regulate pathogenic or protective host response patterns following virus infection. Using SARS-CoV as a model, dynamic transcriptional network changes and disease-associated phenotypes have been identified in different genetic backgrounds, leading to the promise of population-wide discovery of the underpinnings of Coronavirus pathogenesis.",,"['Schäfer, Alexandra', 'Baric, Ralph S.', 'Ferris, Martin T.']",,,,
,PMC,IFIT1: A dual sensor and effector molecule that detects non-2'-O methylated viral RNA and inhibits its translation,http://dx.doi.org/10.1016/j.cytogfr.2014.05.002,PMC4234691,,,"Our understanding of the antiviral actions of IFIT1, one of the most strongly induced interferon stimulated genes (ISGs), has advanced remarkably within the last few years. This review focuses on the recent cellular, biochemical, and structural discoveries that have provided new insight as to how IFIT1 functions as both a sensor and effector molecule of the cellular innate immune system. IFIT1 can detect viral RNA lacking 2’-O methylation on their cap structures or displaying a 5’-triphosphate moiety and inhibit their translation or sequester them from active replication. Because of these inhibitory actions, many viruses have evolved unique mechanisms to evade IFIT1 to facilitate replication, spread of infection, and disease pathogenesis.",,"Diamond, Michael S.",,,,
,PMC,"Hospital-Associated Outbreak of Middle East Respiratory Syndrome Coronavirus: A Serologic, Epidemiologic, and Clinical Description",http://dx.doi.org/10.1093/cid/ciu359,PMC4834865,,,"BACKGROUND: In April 2012, the Jordan Ministry of Health investigated an outbreak of lower respiratory illnesses at a hospital in Jordan; 2 fatal cases were retrospectively confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) to be the first detected cases of Middle East respiratory syndrome (MERS-CoV). METHODS: Epidemiologic and clinical characteristics of selected potential cases were assessed through serum blood specimens, medical record reviews, and interviews with surviving outbreak members, household contacts, and healthcare personnel. Cases of MERS-CoV infection were identified using 3 US Centers for Disease Control and Prevention serologic tests for detection of anti–MERS-CoV antibodies. RESULTS: Specimens and interviews were obtained from 124 subjects. Seven previously unconfirmed individuals tested positive for anti–MERS-CoV antibodies by at least 2 of 3 serologic tests, in addition to 2 fatal cases identified by rRT-PCR. The case-fatality rate among the 9 total cases was 22%. Six subjects were healthcare workers at the outbreak hospital, yielding an attack rate of 10% among potentially exposed outbreak hospital personnel. There was no evidence of MERS-CoV transmission at 2 transfer hospitals having acceptable infection control practices. CONCLUSIONS: Novel serologic tests allowed for the detection of otherwise unrecognized cases of MERS-CoV infection among contacts in a Jordanian hospital-associated respiratory illness outbreak in April 2012, resulting in a total of 9 test-positive cases. Serologic results suggest that further spread of this outbreak to transfer hospitals did not occur. Most subjects had no major, underlying medical conditions; none were on hemodialysis. Our observed case-fatality rate was lower than has been reported from outbreaks elsewhere.",,"['Al-Abdallat, Mohammad Mousa', 'Payne, Daniel C.', 'Alqasrawi, Sultan', 'Rha, Brian', 'Tohme, Rania A.', 'Abedi, Glen R.', 'Nsour, Mohannad Al', 'Iblan, Ibrahim', 'Jarour, Najwa', 'Farag, Noha H.', 'Haddadin, Aktham', 'Al-Sanouri, Tarek', 'Tamin, Azaibi', 'Harcourt, Jennifer L.', 'Kuhar, David T.', 'Swerdlow, David L.', 'Erdman, Dean D.', 'Pallansch, Mark A.', 'Haynes, Lia M.', 'Gerber, Susan I.']",,,,
,PMC,"Rotavirus strains in neglected animal species including lambs, goats and camelids",http://dx.doi.org/10.1007/s13337-014-0203-2,PMC4188177,,,"Surveillance of rotavirus infections and circulating strains in small ruminants (i.e. lambs, goats and camelids) has been a neglected research area in the past. However, recent years that have seen an intensification of surveillance in humans and livestock animals, where vaccines to reduce disease burden caused by Rotavirus A (RVA) are available, led to the efforts to better understand the epidemiology, ecology and evolution of RVA strains in other hosts, including lambs, goats and camelids. The aim of this review is to provide an update of the epidemiology and strain diversity of RV strains in these species through searching for relevant information in public data bases.",,"['Papp, Hajnalka', 'Malik, Yashpal S.', 'Farkas, Szilvia L.', 'Jakab, Ferenc', 'Martella, Vito', 'Bányai, Krisztián']",,,,
,PMC,From quarantine to quality,http://dx.doi.org/10.1503/cmaj.131369,PMC4016098,,,,,"Wobeser, Wendy L.",,,,
,PMC,Transactivation of programmed ribosomal frameshifting by a viral protein,http://dx.doi.org/10.1073/pnas.1321930111,PMC4040542,,,"Programmed −1 ribosomal frameshifting (−1 PRF) is a widely used translational mechanism facilitating the expression of two polypeptides from a single mRNA. Commonly, the ribosome interacts with an mRNA secondary structure that promotes −1 frameshifting on a homopolymeric slippery sequence. Recently, we described an unusual −2 frameshifting (−2 PRF) signal directing efficient expression of a transframe protein [nonstructural protein 2TF (nsp2TF)] of porcine reproductive and respiratory syndrome virus (PRRSV) from an alternative reading frame overlapping the viral replicase gene. Unusually, this arterivirus PRF signal lacks an obvious stimulatory RNA secondary structure, but as confirmed here, can also direct the occurrence of −1 PRF, yielding a third, truncated nsp2 variant named “nsp2N.” Remarkably, we now show that both −2 and −1 PRF are transactivated by a protein factor, specifically a PRRSV replicase subunit (nsp1β). Embedded in nsp1β’s papain-like autoproteinase domain, we identified a highly conserved, putative RNA-binding motif that is critical for PRF transactivation. The minimal RNA sequence required for PRF was mapped within a 34-nt region that includes the slippery sequence and a downstream conserved CCCANCUCC motif. Interaction of nsp1β with the PRF signal was demonstrated in pull-down assays. These studies demonstrate for the first time, to our knowledge, that a protein can function as a transactivator of ribosomal frameshifting. The newly identified frameshifting determinants provide potential antiviral targets for arterivirus disease control and prevention. Moreover, protein-induced transactivation of frameshifting may be a widely used mechanism, potentially including previously undiscovered viral strategies to regulate viral gene expression and/or modulate host cell translation upon infection.",,"['Li, Yanhua', 'Treffers, Emmely E.', 'Napthine, Sawsan', 'Tas, Ali', 'Zhu, Longchao', 'Sun, Zhi', 'Bell, Susanne', 'Mark, Brian L.', 'van Veelen, Peter A.', 'van Hemert, Martijn J.', 'Firth, Andrew E.', 'Brierley, Ian', 'Snijder, Eric J.', 'Fang, Ying']",,,,
,PMC,PNAS Plus Significance Statements,http://dx.doi.org/10.1073/pnas.ss11119,PMC4024887,,,,,,,,,
,PMC,In This Issue,http://dx.doi.org/10.1073/iti1914111,PMC4024877,,,,,,,,,
,PMC,The role of viral persistence in flavivirus biology,http://dx.doi.org/10.1111/2049-632X.12178,PMC4154581,,,"In nature, vector-borne flaviviruses are persistently cycled between either the tick or mosquito vector and small mammals such as rodents, skunks, and swine. These viruses account for considerable human morbidity and mortality worldwide. Increasing and substantial evidence of viral persistence in humans, which includes the isolation of RNA by RT-PCR and infectious virus by culture, continues to be reported. Viral persistence can also be established in vitro in various human, animal, arachnid and insect cell lines in culture. Although some research has focused on the potential roles of defective virus particles, evasion of the immune response through the manipulation of autophagy and/or apoptosis, the precise mechanism of flavivirus persistence is still not well understood. We propose additional research for further understanding of how viral persistence is established in different systems. Avenues for additional studies include determining if the multifunctional flavivirus protein NS5 has a role in viral persistence, the development of relevant animal models of viral persistence as well as investigating the host responses that allow vector borne flavivirus replication without detrimental effects on infected cells. Such studies might shed more light on the viral-host relationships, and could be used to unravel the mechanisms for establishment of persistence.",,"['Mlera, Luwanika', 'Melik, Wessam', 'Bloom, Marshall E.']",,,,
,PMC,Assessment and improvement of Indian-origin rhesus macaque and Mauritian-origin cynomolgus macaque genome annotations using deep transcriptome sequencing data,http://dx.doi.org/10.1111/jmp.12125,PMC4176519,,,"BACKGROUND: The genome annotations of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques, two of the most common nonhuman primate animal models, are limited. METHODS: We analyzed large-scale macaque RNA-based next-generation sequencing (RNAseq) data to identify un-annotated macaque transcripts. RESULTS: For both macaque species, we uncovered thousands of novel isoforms for annotated genes and thousands of un-annotated intergenic transcripts enriched with non-coding RNAs. We also identified thousands of transcript sequences which are partially or completely ‘missing’ from current macaque genome assemblies. We showed that many newly identified transcripts were differentially expressed during SIV infection of rhesus macaques or during Ebola virus infection of cynomolgus macaques. CONCLUSIONS: For two important macaque species, we uncovered thousands of novel isoforms and un-annotated intergenic transcripts including coding and non-coding RNAs, polyadenylated and non-polyadenylated transcripts. This resource will greatly improve future macaque studies, as demonstrated by their applications in infectious disease studies.",,"['Peng, Xinxia', 'Pipes, Lenore', 'Xiong, Hao', 'Green, Richard R.', 'Jones, Daniel C.', 'Ruzzo, Walter L.', 'Schroth, Gary P.', 'Mason, Christopher E.', 'Palermo, Robert E.', 'Katze, Michael G.']",,,,
,PMC,"The NIAID Integrated Research Facility at Frederick, Maryland: A unique international resource to facilitate medical countermeasure development for BSL-4 pathogens",http://dx.doi.org/10.1111/2049-632X.12171,PMC4106974,,,"Scientists at the National Institute of Allergy and Infectious Diseases Integrated Research Facility at Fort Detrick, Frederick, Maryland coordinate and facilitate preclinical research on infectious diseases to develop medical countermeasures for high consequence pathogens. This facility is unique in that it is the only maximum containment laboratory in the world where conventional and molecular medical imaging equipment are incorporated into the design of the facility. This capability provides investigators with unique tools to dissect disease pathogenesis, evaluate the ability of animal models to recapitulate human disease, and test candidate countermeasures. Importantly, advanced molecular imaging has the potential to provide alternative endpoints to lethality. By using these alternative endpoints, investigators can reduce the number of animals used in experiments and evaluate countermeasures in sublethal models. With the incorporation of medical imaging modalities, a clinical laboratory modeled after those existing in hospitals, and a highly trained veterinary medicine team, IRF Frederick is uniquely suited to advance our understanding of emerging infectious diseases and to facilitate the development of medical countermeasures and clinical care paradigms previously considered impossible.",,"['Jahrling, Peter B.', 'Keith, Lauren', 'St. Claire, Marisa', 'Johnson, Reed F.', 'Bollinger, Laura', 'Lackemeyer, Matthew G.', 'Hensley, Lisa E.', 'Kindrachuk, Jason', 'Kuhn, Jens H.']",,,,
,PMC,Improving health services for African migrants in China: A health diplomacy perspective,http://dx.doi.org/10.1080/17441692.2014.908935,PMC4089857,,,"Global health has been an increasingly prominent component of foreign policy in the last decade. The term health diplomacy has been used to describe this growing interface between foreign policy and global health, and it encompasses both the concept of using health to further foreign policy objectives, as well as the idea that diplomatic tools can be helpful for attaining public health goals. The Chinese presence in Africa has grown in the last 15 years, generating increased interest in Sino-African relations. While much has been written in recent years about the Chinese presence in Africa, the growing numbers of Africans in China have attracted considerably less attention. Many are small-scale traders and might be expected to face many of the health challenges common among foreign migrants, but their health needs have been largely unrecognised. In this paper, we consider how a health diplomacy approach could be applied to African migrants in China, and the potential advantages and limitations of this strategy. We identify areas of overlap between public health, trade, and foreign policy goals that can be emphasised to generate support for improved services for African migrants in China and to engage partners from a diversity of sectors.",,"['McLaughlin, Megan M.', 'Lee, Margaret C.', 'Hall, Brian J.', 'Bulterys, Marc', 'Ling, Li', 'Tucker, Joseph D.']",,,,
,PMC,Comparison of xTAG Respiratory Virus Panel and Verigene Respiratory Virus Plus for Detecting Influenza Virus and Respiratory Syncytial Virus,http://dx.doi.org/10.1002/jcla.21738,PMC6807105,,,"BACKGROUND: Nucleic acid amplification tests have allowed simultaneous detection of multiple respiratory viruses. METHODS: We compared the results of a liquid bead array xTAG Respiratory Virus Panel (RVP; (Luminex Corporation, Toronto, Canada) and a solid microarray Verigene Respiratory Virus Plus (RV+; Nanosphere, Northbrook, IL) for the detection of influenza A virus (INF A), influenza B virus (INF B), and respiratory syncytial virus (RSV) in 170 respiratory specimens from hospitalized patients. RESULTS: Overall, xTAG RVP demonstrated sensitivities and specificities of 97.6 and 100% for INF A, 100 and 99.4% for INF B, and 100 and 100% for RSV, while the Verigene RV+ test sensitivities and specificities were 95.1 and 98.5%, 100.0 and 99.4%, and 97.1 and 100%, respectively. There were no significant differences in the area under the curves between the two assays for each virus (P = 0.364 for INF A, P = 1.000 for INF B, P = 0.317 for RSV). Comparing the results of two assays, discordant results were present mostly due to subtype assignments and identification of coinfections. The detection of viruses was not significantly different (P = 1.000) and the virus/subtype assignment showed good agreement with kappa coefficients of 0.908. CONCLUSION: The xTAG RVP and Verigene RV+ showed high sensitivities and specificities, and good overall agreement in detection and identification of INF and RSV. These assays can be used in clinical settings for a reliable detection of respiratory viruses found commonly in hospitalized patients.",,"['Hwang, Sang Mee', 'Lim, Mi Suk', 'Han, Minsuk', 'Hong, Yun Ji', 'Kim, Taek Soo', 'Lee, Hye Ryun', 'Song, Eun Young', 'Park, Kyoung Un', 'Song, Junghan', 'Kim, Eui Chong']",,,,
,PMC,SV40 Large T antigen induces ISGs through ATR Kinase,http://dx.doi.org/10.4049/jimmunol.1303470,PMC4078001,,,"Polyomaviruses encode a Large T antigen (LT), a multifunctional protein essential for the regulation of both viral and host cell gene expression and productive viral infection. Previously, we have shown that stable expression of LT protein results in upregulation of genes involved in the interferon induction and signaling pathway. In this study, we focus on the cellular signaling mechanism that leads to the induction of interferon (IFN) responses by LT. Our results show that ectopic expression of Simian virus 40 (SV40) LT results in the induction of interferon-stimulated genes (ISGs) in human fibroblasts and confers an antiviral state. We describe a LT-initiated DNA-damage response (DDR) that activates IRF1 causing IFNβ production and consequent ISG expression in human cells. This IFNβ and ISG induction is dependent on ATM and Rad3 related (ATR) kinase, but independent of ataxia-telangiectasia mutated (ATM). ATR kinase inhibition using a selective kinase inhibitor (ETP-46464) caused a decrease in IRF1 stabilization and ISG expression. Furthermore, expression of a mutant LT that does not induce DDR, does not induce IFNβ and ISGs. These results show that in the absence of viral infection, LT-initiated activation of ATR-dependent DDR is sufficient for the induction of an IFNβ-mediated innate immune response in human cells. Thus, we have uncovered a novel and critical role for ATR as a mediator of antiviral responses utilizing LT.",,"['Forero, Adriana', 'Giacobbi, Nicholas S.', 'McCormick, Kevin D.', 'Gjoerup, Ole V.', 'Bakkenist, Christopher J.', 'Pipas, James M.', 'Sarkar, Saumendra N.']",,,,
,PMC,The R35 residue of the influenza A virus NS1 protein has minimal effects on nuclear localization but alters virus replication through disrupting protein dimerization,http://dx.doi.org/10.1016/j.virol.2014.04.012,PMC4095983,,,"The influenza A virus NS1 protein has a nuclear localization sequence (NLS) in the amino terminal region. This NLS overlaps sequences that are important for RNA binding as well as protein dimerization. To assess the significance of the NS1 NLS on influenza virus replication, the NLS amino acids were individually mutated to alanines and recombinant viruses encoding these mutations were rescued. Viruses containing NS1 proteins with mutations at R37, R38 and K41 displayed minimal changes in replication or NS1 protein nuclear localization. Recombinant viruses encoding NS1 R35A were not recovered but viruses containing second site mutations at position D39 in addition to the R35A mutation were isolated. The mutations at position 39 were shown to partially restore NS1 protein dimerization but had minimal effects on nuclear localization. These data indicate the amino acids in the NS1 NLS region play a more important role in protein dimerization compared to nuclear localization.",,"['Lalime, Erin N.', 'Pekosz, Andrew']",,,,
,PMC,Azapropellanes with Anti-Influenza A Virus Activity,http://dx.doi.org/10.1021/ml500108s,PMC4094260,,,"[Image: see text] The synthesis of several [4,4,3], [4,3,3], and [3,3,3]azapropellanes is reported. Several of the novel amines displayed low-micromolar activities against an amantadine-resistant H1N1 strain, but they did not show activity against an amantadine-sensitive H3N2 strain. None of the tested compounds inhibit the influenza A/M2 proton channel function. Most of the compounds did not show cytotoxicity for MDCK cells.",,"['Torres, Eva', 'Leiva, Rosana', 'Gazzarrini, Sabrina', 'Rey-Carrizo, Matías', 'Frigolé-Vivas, Marta', 'Moroni, Anna', 'Naesens, Lieve', 'Vázquez, Santiago']",,,,
,PMC,Structural and Functional Correlates of Enhanced Anti-viral Immunity Generated by Heteroclitic CD8 T Cell Epitopes(),http://dx.doi.org/10.4049/jimmunol.1400111,PMC4052115,,,"Peptides that bind poorly to MHC class I molecules often elicit low functional avidity T cell responses. Peptide modification by altering the anchor residue facilitates increased binding affinity and may elicit T cells with increased functional avidity towards the native epitope (“heteroclitic”). This augmented MHC binding is likely to increase the half-life and surface density of the heteroclitic complex but precisely how this enhanced T cell response occurs in vivo is not known. Furthermore, the ideal heteroclitic epitope will elicit T cell responses that completely cross-react with the native epitope, maximizing protection and minimizing undesirable off-target effects. Such epitopes have been difficult to identify. Here, using mice infected with a murine coronavirus that encodes epitopes that elicit high (S510, CSLWNGPHL) and low (S598, RCQIFANI) functional avidity responses, we show that increased expression of peptide S598 but not S510 generated T cells with enhanced functional avidity. Thus immune responses can be augmented towards T cell epitopes with low functional avidity by increasing antigen density. We also identified a heteroclitic epitope (RCVIFANI) that elicited a T cell response with nearly complete cross-reactivity with native epitope and demonstrated increased MHC-peptide abundance compared to native S598. Structural and thermal melt analyses indicated that the Q600V substitution enhanced stability of the peptide-MHC complex without greatly altering the antigenic surface, resulting in highly cross-reactive T cell responses. Our data highlight that increased pMHC complex display contributes to heteroclitic epitope efficacy and describe parameters for maximizing immune responses that cross-react with the native epitope.",,"['Trujillo, Jonathan A.', 'Gras, Stephanie', 'Twist, Kelly-Anne', 'Croft, Nathan P.', 'Channappanavar, Rudragouda', 'Rossjohn, Jamie', 'Purcell, Anthony W.', 'Perlman, Stanley']",,,,
,PMC,Targeted Small Interfering RNA-Immunoliposomes as a Promising Therapeutic Agent against Highly Pathogenic Avian Influenza A (H5N1) Virus Infection,http://dx.doi.org/10.1128/AAC.02768-13,PMC3993214,,,"This study describes a proof-of-concept study on the use of small interfering RNA (siRNA)-immunoliposomes as a therapeutic agent against H5N1 influenza virus infection. siRNA specific for influenza virus nucleoprotein (NP) mRNA was employed as the key antiviral agent to inhibit viral replication in this study. A humanized single-chain Fv antibody (huscFv) against the hemagglutinin (HA) of H5N1 highly pathogenic avian influenza virus (HPAI) was used as the targeting molecule to HA of H5N1 virus, which is abundantly expressed on the surface of infected cells (the HA target cells). The huscFv was applied to cationic polyethylene glycol-conjugated 3β-[N-(N′,N′-dimethylaminoethane) carbamoyl] cholesterol–dioleoylphosphatidyl ethanolamine (PEGylated DC-Chol–DOPE) liposomes to generate immunoliposomes for siRNA delivery. The immunoliposomes were shown to specifically bind HA-expressing Sf9 cells and demonstrated enhanced siRNA transfection efficiency. The siRNA transfection efficiency was significantly reduced after preincubation of the HA target cells with an excess amount of free huscFv. These results therefore demonstrated that the enhanced siRNA delivery by use of immunoliposomes was mediated via targeting by huscFv. Furthermore, the siRNA silencing effect was more pronounced when the immunoliposomes were administered 6 to 12 h post-H5N1 infection in MDCK cells compared with the nontargeted liposomes. This proof-of-concept study may contribute to the future design and development of an siRNA delivery system for combating viral infectious diseases in humans.",,"['Khantasup, Kannika', 'Kopermsub, Phikulthong', 'Chaichoun, Kridsada', 'Dharakul, Tararaj']",,,,
,PMC,"Survival of Airborne MS2 Bacteriophage Generated from Human Saliva, Artificial Saliva, and Cell Culture Medium",http://dx.doi.org/10.1128/AEM.00056-14,PMC3993287,,,"Laboratory studies of virus aerosols have been criticized for generating airborne viruses from artificial nebulizer suspensions (e.g., cell culture media), which do not mimic the natural release of viruses (e.g., from human saliva). The objectives of this study were to determine the effect of human saliva on the infectivity and survival of airborne virus and to compare it with those of artificial saliva and cell culture medium. A stock of MS2 bacteriophage was diluted in one of three nebulizer suspensions, aerosolized, size selected (100 to 450 nm) using a differential mobility analyzer, and collected onto gelatin filters. Uranine was used as a particle tracer. The resulting particle size distribution was measured using a scanning mobility particle sizer. The amounts of infectious virus, total virus, and fluorescence in the collected samples were determined by infectivity assays, quantitative reverse transcription-PCR (RT-PCR), and spectrofluorometry, respectively. For all nebulizer suspensions, the virus content generally followed a particle volume distribution rather than a number distribution. The survival of airborne MS2 was independent of particle size but was strongly affected by the type of nebulizer suspension. Human saliva was found to be much less protective than cell culture medium (i.e., 3% tryptic soy broth) and artificial saliva. These results indicate the need for caution when extrapolating laboratory results, which often use artificial nebulizer suspensions. To better assess the risk of airborne transmission of viral diseases in real-life situations, the use of natural suspensions such as saliva or respiratory mucus is recommended.",,"['Zuo, Zhili', 'Kuehn, Thomas H.', 'Bekele, Aschalew Z.', 'Mor, Sunil K.', 'Verma, Harsha', 'Goyal, Sagar M.', 'Raynor, Peter C.', 'Pui, David Y. H.']",,,,
,PMC,Prevalence of rotavirus (GARV) and coronavirus (BCoV) associated with neonatal diarrhea in calves in western Algeria,http://dx.doi.org/10.12980/APJTB.4.2014C778,PMC4025335,,,"OBJECTIVE: To study the prevalence of bovine group A rotavirus (GARV) and bovine coronavirus (BCoV) in diarrheic feces from calves and the sensitive's parameters such as age group and sex. METHODS: Feces samples from 82 diarrheic dairy calves from farms around Tiaret (Western Algeria) were collected. These samples were tested by ELISA assay. RESULTS: The results showed that the prevalence of rotavirus and coronavirus infection are 14.63% (12.2% alone and 2.43% associated with bovine coronavirus) and 20.73% (18.3% alone and 2.43% associated with GARV), respectively. CONCLUSIONS: The present study demonstrates that the both BCoV and GARV are involved in the neonatal calves' diarrhea, where the frequency of BCoV is clearly higher than that of GARV.",,"['Ammar, Selles Sidi Mohammed', 'Mokhtaria, Kouidri', 'Tahar, Belhamiti Belkacem', 'Amar, Ait Amrane', 'Redha, Benia Ahmed', 'Yuva, Bellik', 'Mohamed, Hammoudi Si', 'Abdellatif, Niar', 'Laid, Boukrâa']",,,,
,PMC,"Are animals a bane for the spread of the deadly malady, the corona virus (MERS)?",http://dx.doi.org/10.12980/APJTB.4.2014C1220,PMC4025316,,,,,"['Gundamaraju, Rohit', 'Vemuri, Ravi Chandra', 'Hwi, Kim Kah']",,,,
,PMC,Fatal hemorrhagic-necrotizing pancreatitis associated with pancreatic and hepatic lipidosis in an obese Asian palm civet (Paradoxurus hermaphroditus),http://dx.doi.org/10.12980/APJTB.4.2014C915,PMC4025281,,,"Asian palm civets (Paradoxurus hermaphroditus), or toddy cats, belong to the family Viverridae. Little is known about the pathology of these animals and few articles have been published, mainly concerning their important role as wild reservoir hosts for severe infectious diseases of domestic animals and human beings. A 4-year-old, female Asian palm civet was found dead by the owner. At necropsy, large amount of adipose tissue was found in the subcutis and in the peritoneal cavity. Most of the pancreas appeared red, translucent. Hepatomegaly, discoloration of the liver were evident, with multifocal areas of degeneration, characterized by white nodular lesions. Histologically, the pancreas showed severe interstitial and perilobular necrosis and extensive haemorrhages, with separation of the interstitium, mild reactive inflammation at the periphery of the pancreatic lobules. Liver showed multifocal foci of vacuolar degeneration, lipidic accumulation, sometimes associated to hepatocyte necrosis. A diagnosis of acute severe hemorrhagic-necrotizing pancreatitis (or acute pancreatic necrosis) associated with pancreatic and hepatic lipidosis was made. To the best of our knowledge, this represents the first case report of acute lethal pancreatitis in an Asian palm civet. Although the exact cause of the disease remains undetermined, a hypothesis of the cause and pathogenesis is discussed, pointing out dietary indiscretion and consequent overweight as possible important risk factors.",,"['Laura, Bongiovanni', 'Nicola, Di Girolamo', 'Alessandro, Montani', 'Leonardo, Della Salda', 'Paolo, Selleri']",,,,
,PMC,International Health Regulations (2005): taking stock,http://dx.doi.org/10.2471/BLT.14.138990,PMC4007135,,,,,"Nuttall, Isabelle",,,,
,PMC,The real-life effectiveness of palivizumab for reducing hospital admissions for respiratory syncytial virus in infants residing in Nunavut,,PMC4128465,,,"BACKGROUND/OBJECTIVE: Nunavut has the highest hospitalization rates for respiratory syncytial virus (RSV) worldwide, with rates of 166 per 1000 live births per year <1 year of age. Palivizumab was implemented in Nunavut primarily for premature infants, or those with hemodynamically significant cardiac or chronic lung disease; however, the effectiveness of the program is unknown. The objective of the present multisite, hospital-based surveillance study was to estimate the effectiveness of palivizumab in infants <6 months of age in Nunavut for the 2009 and 2010 RSV seasons. METHODS: Infants identified as palivizumab candidates who were <6 months of age were compared with all admissions for lower respiratory tract infection through multisite, hospital-based surveillance documenting the adequacy of palivizumab prophylaxis, admission for lower respiratory tract infection and the results of RSV testing. The OR for RSV admission in unprophylaxed infants was compared with those who were prophylaxed, and the effectiveness of palivizumab was estimated. RESULTS: Within the study cohort (n=101) during the two RSV seasons, five of the 10 eligible infants who did not receive adequate prophylaxis were admitted with RSV while two of the 91 infants <6 months of age eligible for palivizumab who were adequately prophylaxed were hospitalized with RSV (OR 22.3 [95% CI 3.8 to 130]; P=0.0005). The estimated effectiveness of palivizumab for the cohort was as high as 96%. Eight eligible infants were missed by the program and did not receive prophylaxis. CONCLUSION: Palivizumab was highly effective in reducing hospitalizations due to RSV infection in Nunavut. Further efforts need to be made to ensure that all eligible infants are identified.",,"['Banerji, Anna', 'Panzov, Vladimir', 'Young, Michael', 'Lee, Bonita E', 'Mamdani, Muhammad', 'Giles, B Louise', 'Dennis, Marguerite', 'Morel, Johanne', 'Bisson, Danny', 'Paes, Bosco A', 'Hui, Charles', 'Mahony, Jim']",,,,
,PMC,The Central RAS and Sympathetic Nerve Activity in Chronic Heart Failure,http://dx.doi.org/10.1042/CS20130294,PMC4053944,,,"Chronic heart failure (CHF) is a multi-factorial disease process that is characterized by over activation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system. Both of these systems are chronically activated in CHF. The RAAS consists of an excitatory arm involving Angiotensin II (Ang II), Angiotensin Converting Enzyme (ACE), and the Ang II type 1 Receptor (AT1R). The RAAS also consists of a protective arm consisting of Angiotensin-1-7 (Ang -1-7), the Ang II type 2 receptor (AT2R), ACE2 and the mas receptor. Sympathoexcitation in CHF is driven, in large part, by an imbalance of these two arms, with an increase in the Ang II-AT1R-ACE arm and a decrease in the AT2R-ACE2 arm. This imbalance is manifested in cardiovascular-control regions of the brain such as the rostral ventrolateral medulla and paraventricular nucleus in the hypothalamus. This review focuses on current literature that describes the components of these two arms of the RAAS, and their imbalance in the CHF state. Moreover, this review provides additional evidence for the relevance of ACE2 and Ang-1-7 as key players in the regulation of central sympathetic outflow in CHF. Finally we also examine the effects of exercise training as a therapeutic strategy and the molecular mechanisms at play in CHF, in part, because of the ability of exercise training to restore the balance of the RAAS axis and sympathetic outflow.",,"['Zucker, Irving H.', 'Xiao, Liang', 'Haack, Karla K.V.']",,,,
,PMC,Assessing Knowledge and Application of Emergency Risk Communication Principles Among Public Health Workers in China,http://dx.doi.org/10.1017/dmp.2014.29,PMC4675457,,,"OBJECTIVE: Since 2003, the Chinese National Health and Family Planning Commission (formerly the Ministry of Health) has implemented changes to more effectively communicate risk during public health emergencies. In spite of ongoing improvements, provincial and sub-provincial leaders face barriers, such as established modes of operation, lack of training, shortage of trained risk communicators, and limited understanding and willingness of recipients to mitigate risks. METHODS: We assessed the current status of and barriers to risk communication knowledge and practice among public health practitioners in China. We designed the survey questionnaire to capture information related to the risk communication core capacities required by international health regulations and common risk communication principles. RESULTS: Our findings showed that risk communication training has successfully developed an awareness of risk communication principles and the ability to implement those principles in practice in China. CONCLUSIONS: Future efforts should focus on areas such as a dedicated risk communication workforce, requirements that public health agencies develop a risk communication plan, and additional training for public health practitioners and their partners. It is critical that the infectious diseases prevention and control law be amended to grant provincial and local public health agencies more autonomy to release information.",,"['Cope, James R.', 'Frost, Melinda', 'Richun, Li', 'Xie, Ruiqian']",,,,
,PMC,Administration of Luteinizing Hormone Releasing Hormone Agonist for Synchronization of Estrus and Generation of Pseudopregnancy for Embryo Transfer in Rats,,PMC4128560,,,"In the past decade, the use of genetically engineered rats has increased exponentially; therefore, the ability to perform embryo transfer (ET) in rats to rederive, reanimate, or create mutant rat lines is increasingly important. However, the successful generation of pseudopregnant female rats for ET represents a limiting factor. We here evaluated the subcutaneous administration of 40 µg luteinizing hormone releasing hormone agonist (LHRHa) for estrus synchronization during the development and implementation of a rat ET program. Our first experiment assessed endogenous estrus cycling patterns by examining vaginal cytology without administration of LHRHa in 5-wk-old peripubertal Sprague–Dawley female rats. These rats then received LHRHa at approximately 7 wk of age; 57% of the rats were synchronized in proestrus or estrus as assessed by vaginal cytology 96 h later. In a second experiment, 8-wk-old virgin, unmanipulated Sprague–Dawley female rats received LHRHa; 55% were synchronized in proestrus or estrus 96 h later. Copulatory plugs were confirmed in 28% and 82% of the rats that had been synchronized in the first and second experiments, respectively, and mated with vasectomized male rats. Embryo transfer surgery was performed, and live pups were born from both fresh and cryopreserved transgenic rat embryos. Our results indicate that subcutaneous administration of 40 µg LHRHa followed by examination of vaginal cytology 96 h later is an effective technique to generate multiple pseudopregnant recipient rats for use in an ET program.",,"['Borjeson, Tiffany M', 'Pang, Jassia', 'Fox, James G', 'García, Alexis']",,,,
,PMC,Type I IFN signaling in CD8(–) DCs impairs Th1-dependent malaria immunity,http://dx.doi.org/10.1172/JCI70698,PMC4038565,,,"Many pathogens, including viruses, bacteria, and protozoan parasites, suppress cellular immune responses through activation of type I IFN signaling. Recent evidence suggests that immune suppression and susceptibility to the malaria parasite, Plasmodium, is mediated by type I IFN; however, it is unclear how type I IFN suppresses immunity to blood-stage Plasmodium parasites. During experimental severe malaria, CD4(+) Th cell responses are suppressed, and conventional DC (cDC) function is curtailed through unknown mechanisms. Here, we tested the hypothesis that type I IFN signaling directly impairs cDC function during Plasmodium infection in mice. Using cDC-specific IFNAR1-deficient mice, and mixed BM chimeras, we found that type I IFN signaling directly affects cDC function, limiting the ability of cDCs to prime IFN-γ–producing Th1 cells. Although type I IFN signaling modulated all subsets of splenic cDCs, CD8(–) cDCs were especially susceptible, exhibiting reduced phagocytic and Th1-promoting properties in response to type I IFNs. Additionally, rapid and systemic IFN-α production in response to Plasmodium infection required type I IFN signaling in cDCs themselves, revealing their contribution to a feed-forward cytokine-signaling loop. Together, these data suggest abrogation of type I IFN signaling in CD8(–) splenic cDCs as an approach for enhancing Th1 responses against Plasmodium and other type I IFN–inducing pathogens.",,"['Haque, Ashraful', 'Best, Shannon E.', 'Montes de Oca, Marcela', 'James, Kylie R.', 'Ammerdorffer, Anne', 'Edwards, Chelsea L.', 'de Labastida Rivera, Fabian', 'Amante, Fiona H.', 'Bunn, Patrick T.', 'Sheel, Meru', 'Sebina, Ismail', 'Koyama, Motoko', 'Varelias, Antiopi', 'Hertzog, Paul J.', 'Kalinke, Ulrich', 'Gun, Sin Yee', 'Rénia, Laurent', 'Ruedl, Christiane', 'MacDonald, Kelli P.A.', 'Hill, Geoffrey R.', 'Engwerda, Christian R.']",,,,
,PMC,Coronavirus Replicase-Reporter Fusions Provide Quantitative Analysis of Replication and Replication Complex Formation,http://dx.doi.org/10.1128/JVI.00021-14,PMC4019139,,,"The replication of coronaviruses occurs in association with multiple virus-induced membrane structures that evolve during the course of infection; however, the dynamics of this process remain poorly understood. Previous studies of coronavirus replication complex organization and protein interactions have utilized protein overexpression studies and immunofluorescence of fixed cells. Additionally, live-imaging studies of coronavirus replicase proteins have used fluorescent reporter molecules fused to replicase proteins, but expressed from nonnative locations, mostly late-transcribed subgenomic mRNAs, in the presence or absence of the native protein. Thus, the timing and targeting of native replicase proteins expressed in real time from native locations in the genome remain unknown. In this study, we tested whether reporter molecules could be expressed from the replicase polyprotein of murine hepatitis virus as fusions with nonstructural protein 2 or 3 and whether such reporters could define the targeting and activity of replicase proteins during infection. We demonstrate that the fusion of green fluorescent protein and firefly luciferase with either nonstructural protein 2 or 3 is tolerated and that these reporter-replicase fusions can be used to quantitate replication complex formation and virus replication. The results show that the replicase gene has flexibility to accommodate a foreign gene addition and can be used directly to study replicase complex formation and evolution during infection as well as to provide highly sensitive and specific markers for protein translation and genome replication. IMPORTANCE Coronaviruses are a family of enveloped, positive-sense RNA viruses that are important agents of disease, including severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus. Replication is associated with multiple virus-induced membrane structures that evolve during infection; however, the dynamics of this process remain poorly understood. In this study, we tested whether reporter molecules expressed from native locations within the replicase polyprotein of murine hepatitis virus as fusions with nonstructural proteins could define the expression and targeting of replicase proteins during infection in live cells. We demonstrate that the replicase gene tolerates the introduction of green fluorescent protein or firefly luciferase as fusions with replicase proteins. These viruses allow early quantitation of virus replication as well as real-time measurement of replication complexes.",,"['Freeman, Megan Culler', 'Graham, Rachel L.', 'Lu, Xiaotao', 'Peek, Christopher T.', 'Denison, Mark R.']",,,,
,PMC,Coronaviruses: Important Emerging Human Pathogens,http://dx.doi.org/10.1128/JVI.03488-13,PMC4019136,,,"The identification of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 reaffirmed the importance of understanding how coronaviruses emerge, infect, and cause disease. By comparing what is known about severe acute respiratory syndrome coronavirus (SARS-CoV) to what has recently been found for MERS-CoV, researchers are discovering similarities and differences that may be important for pathogenesis. Here we discuss what is known about each virus and what gaps remain in our understanding, especially concerning MERS-CoV.",,"['Coleman, Christopher M.', 'Frieman, Matthew B.']",,,,
,PMC,The Host Protease TMPRSS2 Plays a Major Role in In Vivo Replication of Emerging H7N9 and Seasonal Influenza Viruses,http://dx.doi.org/10.1128/JVI.03677-13,PMC4019123,,,"Proteolytic cleavage of the hemagglutinin (HA) protein is essential for influenza A virus (IAV) to acquire infectivity. This process is mediated by a host cell protease(s) in vivo. The type II transmembrane serine protease TMPRSS2 is expressed in the respiratory tract and is capable of activating a variety of respiratory viruses, including low-pathogenic (LP) IAVs possessing a single arginine residue at the cleavage site. Here we show that TMPRSS2 plays an essential role in the proteolytic activation of LP IAVs, including a recently emerged H7N9 subtype, in vivo. We generated TMPRSS2 knockout (KO) mice. The TMPRSS2 KO mice showed normal reproduction, development, and growth phenotypes. In TMPRSS2 KO mice infected with LP IAVs, cleavage of HA was severely impaired, and consequently, the majority of LP IAV progeny particles failed to gain infectivity, while the viruses were fully activated proteolytically in TMPRSS2(+/+) wild-type (WT) mice. Accordingly, in contrast to WT mice, TMPRSS2 KO mice were highly tolerant of challenge infection by LP IAVs (H1N1, H3N2, and H7N9) with ≥1,000 50% lethal doses (LD(50)) for WT mice. On the other hand, a high-pathogenic H5N1 subtype IAV possessing a multibasic cleavage site was successfully activated in the lungs of TMPRSS2 KO mice and killed these mice, as observed for WT mice. Our results demonstrate that recently emerged H7N9 as well as seasonal IAVs mainly use the specific protease TMPRSS2 for HA cleavage in vivo and, thus, that TMPRSS2 expression is essential for IAV replication in vivo. IMPORTANCE Influenza A virus (IAV) is a leading pathogen that infects and kills many humans every year. We clarified that the infectivity and pathogenicity of IAVs, including a recently emerged H7N9 subtype, are determined primarily by a host protease, TMPRSS2. Our data showed that TMPRSS2 is the key host protease that activates IAVs in vivo through proteolytic cleavage of their HA proteins. Hence, TMPRSS2 is a good target for the development of anti-IAV drugs. Such drugs could also be effective for many other respiratory viruses, including the recently emerged Middle East respiratory syndrome (MERS) coronavirus, because they are also activated by TMPRSS2 in vitro. Consequently, the present paper could have a large impact on the battle against respiratory virus infections and contribute greatly to human health.",,"['Sakai, Kouji', 'Ami, Yasushi', 'Tahara, Maino', 'Kubota, Toru', 'Anraku, Masaki', 'Abe, Masako', 'Nakajima, Noriko', 'Sekizuka, Tsuyoshi', 'Shirato, Kazuya', 'Suzaki, Yuriko', 'Ainai, Akira', 'Nakatsu, Yuichiro', 'Kanou, Kazuhiko', 'Nakamura, Kazuya', 'Suzuki, Tadaki', 'Komase, Katsuhiro', 'Nobusawa, Eri', 'Maenaka, Katsumi', 'Kuroda, Makoto', 'Hasegawa, Hideki', 'Kawaoka, Yoshihiro', 'Tashiro, Masato', 'Takeda, Makoto']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00815-14,PMC4019111,,,,,,,,,
,PMC,Defective Interfering Influenza Virus RNAs: Time To Reevaluate Their Clinical Potential as Broad-Spectrum Antivirals?,http://dx.doi.org/10.1128/JVI.03193-13,PMC4019098,,,"Defective interfering (DI) RNAs are highly deleted forms of the infectious genome that are made by most families of RNA viruses. DI RNAs retain replication and packaging signals, are synthesized preferentially over infectious genomes, and are packaged as DI virus particles which can be transmitted to susceptible cells. Their ability to interfere with the replication of infectious virus in cell culture and their potential as antivirals in the clinic have long been known. However, until now, no realistic formulation has been described. In this review, we consider the early evidence of antiviral activity by DI viruses and, using the example of DI influenza A virus, outline developments that have led to the production of a cloned DI RNA that is highly active in preclinical studies not only against different subtypes of influenza A virus but also against heterologous respiratory viruses. These data suggest the timeliness of reassessing the potential of DI viruses as a novel class of antivirals that may have general applicability.",,"['Dimmock, Nigel J.', 'Easton, Andrew J.']",,,,
,PMC,"Anti-Lyssaviral Activity of Interferons κ and ω from the Serotine Bat, Eptesicus serotinus",http://dx.doi.org/10.1128/JVI.03403-13,PMC4019090,,,"Interferons (IFNs) are cytokines produced by host cells in response to the infection with pathogens. By binding to the corresponding receptors, IFNs trigger different pathways to block intracellular replication and growth of pathogens and to impede the infection of surrounding cells. Due to their key role in host defense against viral infections, as well as for clinical therapies, the IFN responses and regulation mechanisms are well studied. However, studies of type I IFNs have mainly focused on alpha interferon (IFN-α) and IFN-β subtypes. Knowledge of IFN-κ and IFN-ω is limited. Moreover, most studies are performed in humans or mouse models but not in the original host of zoonotic pathogens. Bats are important reservoirs and transmitters of zoonotic viruses such as lyssaviruses. A few studies have shown an antiviral activity of IFNs in fruit bats. However, the function of type I IFNs against lyssaviruses in bats has not been studied yet. Here, IFN-κ and IFN-ω genes from the European serotine bat, Eptesicus serotinus, were cloned and functionally characterized. E. serotinus IFN-κ and IFN-ω genes are intronless and well conserved between microchiropteran species. The promoter regions of both genes contain essential regulatory elements for transcription factors. In vitro studies indicated a strong activation of IFN signaling by recombinant IFN-ω, whereas IFN-κ displayed weaker activation. Noticeably, both IFNs inhibit to different extents the replication of different lyssaviruses in susceptible bat cell lines. The present study provides functional data on the innate host defense against lyssaviruses in endangered European bats. IMPORTANCE We describe here for the first time the molecular and functional characterization of two type I interferons (IFN-κ and -ω) from European serotine bat (Eptesicus serotinus). The importance of this study is mainly based on the fact that very limited information about the early innate immune response against bat lyssaviruses in their natural host serotine bats is yet available. Generally, whereas the antiviral activity of other type I interferons is well studied, the functional involvement of IFN-κ and -ω has not yet been investigated.",,"['He, Xiaocui', 'Korytář, Tomáš', 'Schatz, Juliane', 'Freuling, Conrad M.', 'Müller, Thomas', 'Köllner, Bernd']",,,,
,PMC,3C(pro) of Foot-and-Mouth Disease Virus Antagonizes the Interferon Signaling Pathway by Blocking STAT1/STAT2 Nuclear Translocation,http://dx.doi.org/10.1128/JVI.03668-13,PMC3993825,,,"Foot-and-mouth disease virus (FMDV) causes a highly contagious, debilitating disease in cloven-hoofed animals with devastating economic consequences. To survive in the host, FMDV has evolved to antagonize the host type I interferon (IFN) response. Previous studies have reported that the leader proteinase (L(pro)) and 3C(pro) of FMDV are involved in the inhibition of type I IFN production. However, whether the proteins of FMDV can inhibit type I IFN signaling is less well understood. In this study, we first found that 3C(pro) of FMDV functioned to interfere with the JAK-STAT signaling pathway. Expression of 3C(pro) significantly reduced the transcript levels of IFN-stimulated genes (ISGs) and IFN-stimulated response element (ISRE) promoter activity. The protein level, tyrosine phosphorylation of STAT1 and STAT2, and their heterodimerization were not affected. However, the nuclear translocation of STAT1/STAT2 was blocked by the 3C(pro) protein. Further mechanistic studies demonstrated that 3C(pro) induced proteasome- and caspase-independent protein degradation of karyopherin α1 (KPNA1), the nuclear localization signal receptor for tyrosine-phosphorylated STAT1, but not karyopherin α2, α3, or α4. Finally, we showed that the protease activity of 3C(pro) contributed to the degradation of KPNA1 and thus blocked STAT1/STAT2 nuclear translocation. Taken together, results of our experiments describe for the first time a novel mechanism by which FMDV evolves to inhibit IFN signaling and counteract host innate antiviral responses. IMPORTANCE We show that 3C(pro) of FMDV antagonizes the JAK-STAT signaling pathway by blocking STAT1/STAT2 nuclear translocation. Furthermore, 3C(pro) induces KPNA1 degradation, which is independent of proteasome and caspase pathways. The protease activity of 3C(pro) contributes to the degradation of KPNA1 and governs the ability of 3C(pro) to inhibit the JAK-STAT signaling pathway. This study uncovers a novel mechanism evolved by FMDV to antagonize host innate immune responses.",,"['Du, Yijun', 'Bi, Jingshan', 'Liu, Jiyu', 'Liu, Xing', 'Wu, Xiangju', 'Jiang, Ping', 'Yoo, Dongwan', 'Zhang, Yongguang', 'Wu, Jiaqiang', 'Wan, Renzhong', 'Zhao, Xiaomin', 'Guo, Lihui', 'Sun, Wenbo', 'Cong, Xiaoyan', 'Chen, Lei', 'Wang, Jinbao']",,,,
,PMC,Middle East Respiratory Syndrome Coronavirus 4a Protein Is a Double-Stranded RNA-Binding Protein That Suppresses PACT-Induced Activation of RIG-I and MDA5 in the Innate Antiviral Response,http://dx.doi.org/10.1128/JVI.03649-13,PMC3993821,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen that causes severe disease in human. MERS-CoV is closely related to bat coronaviruses HKU4 and HKU5. Evasion of the innate antiviral response might contribute significantly to MERS-CoV pathogenesis, but the mechanism is poorly understood. In this study, we characterized MERS-CoV 4a protein as a novel immunosuppressive factor that antagonizes type I interferon production. MERS-CoV 4a protein contains a double-stranded RNA-binding domain capable of interacting with poly(I·C). Expression of MERS-CoV 4a protein suppressed the interferon production induced by poly(I·C) or Sendai virus. RNA binding of MERS-CoV 4a protein was required for IFN antagonism, a property shared by 4a protein of bat coronavirus HKU5 but not by the counterpart in bat coronavirus HKU4. MERS-CoV 4a protein interacted with PACT in an RNA-dependent manner but not with RIG-I or MDA5. It inhibited PACT-induced activation of RIG-I and MDA5 but did not affect the activity of downstream effectors such as RIG-I, MDA5, MAVS, TBK1, and IRF3. Taken together, our findings suggest a new mechanism through which MERS-CoV employs a viral double-stranded RNA-binding protein to circumvent the innate antiviral response by perturbing the function of cellular double-stranded RNA-binding protein PACT. PACT targeting might be a common strategy used by different viruses, including Ebola virus and herpes simplex virus 1, to counteract innate immunity. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging and highly lethal human pathogen. Why MERS-CoV causes severe disease in human is unclear, and one possibility is that MERS-CoV is particularly efficient in counteracting host immunity, including the sensing of virus invasion. It will therefore be critical to clarify how MERS-CoV cripples the host proteins that sense viruses and to compare MERS-CoV with its ancestral viruses in bats in the counteraction of virus sensing. This work not only provides a new understanding of the abilities of MERS-CoV and closely related bat viruses to subvert virus sensing but also might prove useful in revealing new strategies for the development of vaccines and antivirals.",,"['Siu, Kam-Leung', 'Yeung, Man Lung', 'Kok, Kin-Hang', 'Yuen, Kit-San', 'Kew, Chun', 'Lui, Pak-Yin', 'Chan, Chi-Ping', 'Tse, Herman', 'Woo, Patrick C. Y.', 'Yuen, Kwok-Yung', 'Jin, Dong-Yan']",,,,
,PMC,Mouse Dipeptidyl Peptidase 4 Is Not a Functional Receptor for Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/JVI.03764-13,PMC3993820,,,"Human dipeptidyl peptidase 4 (hDPP4) was recently identified as the receptor for Middle East respiratory syndrome coronavirus (MERS-CoV) infection, suggesting that other mammalian DPP4 orthologs may also support infection. We demonstrate that mouse DPP4 cannot support MERS-CoV infection. However, employing mouse DPP4 as a scaffold, we identified two critical amino acids (A288L and T330R) that regulate species specificity in the mouse. This knowledge can support the rational design of a mouse-adapted MERS-CoV for rapid assessment of therapeutics.",,"['Cockrell, Adam S.', 'Peck, Kayla M.', 'Yount, Boyd L.', 'Agnihothram, Sudhakar S.', 'Scobey, Trevor', 'Curnes, Nicole R.', 'Baric, Ralph S.', 'Heise, Mark T.']",,,,
,PMC,TMPRSS2 Is a Host Factor That Is Essential for Pneumotropism and Pathogenicity of H7N9 Influenza A Virus in Mice,http://dx.doi.org/10.1128/JVI.03799-13,PMC3993819,,,"Cleavage of the hemagglutinin (HA) by host proteases is essential for the infectivity of influenza viruses. Here, we analyzed the role of the serine protease TMPRSS2, which activates HA in the human respiratory tract, in pathogenesis in a mouse model. Replication of the human H7N9 isolate A/Anhui/1/13 and of human H1N1 and H3N2 viruses was compared in TMPRSS2 knockout (TMPRSS2(−/−)) and wild-type (WT) mice. Knockout of TMPRSS2 expression inhibited H7N9 influenza virus replication in explants of murine tracheas, bronchi, and lungs. H1N1 virus replication was also strongly suppressed in airway explants of TMPRSS2(−/−) mice, while H3N2 virus replication was only marginally affected. H7N9 and H1N1 viruses were apathogenic in TMPRSS2(−/−) mice, whereas WT mice developed severe disease with mortality rates of 100% and 20%, respectively. In contrast, all H3N2 infected TMPRSS2(−/−) and WT mice succumbed to lethal infection. Cleavage analysis showed that H7 and H1 are efficiently activated by TMPRSS2, whereas H3 is less susceptible to the protease. Our data demonstrate that TMPRSS2 is a host factor that is essential for pneumotropism and pathogenicity of H7N9 and H1N1 influenza virus in mice. In contrast, replication of H3N2 virus appears to depend on another, not yet identified protease, supporting the concept that human influenza viruses differ in protease specificity. IMPORTANCE Cleavage of the hemagglutinin (HA) by host proteases is essential for the infectivity of influenza virus, but little is known about its relevance for pathogenesis in mammals. Here, we show that knockout mice that do not express the HA-activating protease TMPRSS2 are resistant to pulmonary disease with lethal outcome when infected with influenza A viruses of subtypes H7N9 and H1N1, whereas they are not protected from lethal H3N2 virus infection. These findings demonstrate that human influenza viruses differ in protease specificity, and that expression of the appropriate protease in respiratory tissues is essential for pneumotropism and pathogenicity. Our observations also demonstrate that HA-activating proteases and in particular TMPRSS2 are promising targets for influenza therapy.",,"['Tarnow, Carolin', 'Engels, Géraldine', 'Arendt, Annika', 'Schwalm, Folker', 'Sediri, Hanna', 'Preuss, Annette', 'Nelson, Peter S.', 'Garten, Wolfgang', 'Klenk, Hans-Dieter', 'Gabriel, Gülsah', 'Böttcher-Friebertshäuser, Eva']",,,,
,PMC,Heat Shock Protein 70 Enhances Mucosal Immunity against Human Norovirus When Coexpressed from a Vesicular Stomatitis Virus Vector,http://dx.doi.org/10.1128/JVI.00019-14,PMC3993811,,,"Human norovirus (NoV) accounts for 95% of nonbacterial gastroenteritis worldwide. Currently, there is no vaccine available to combat human NoV as it is not cultivable and lacks a small-animal model. Recently, we demonstrated that recombinant vesicular stomatitis virus (rVSV) expressing human NoV capsid protein (rVSV-VP1) induced strong immunities in mice (Y. Ma and J. Li, J. Virol. 85:2942–2952, 2011). To further improve the safety and efficacy of the vaccine candidate, heat shock protein 70 (HSP70) was inserted into the rVSV-VP1 backbone vector. A second construct was generated in which the firefly luciferase (Luc) gene was inserted in place of HSP70 as a control for the double insertion. The resultant recombinant viruses (rVSV-HSP70-VP1 and rVSV-Luc-VP1) were significantly more attenuated in cell culture and viral spread in mice than rVSV-VP1. At the inoculation dose of 1.0 × 10(6) PFU, rVSV-HSP70-VP1 triggered significantly higher vaginal IgA than rVSV-VP1 and significantly higher fecal and vaginal IgA responses than rVSV-Luc-VP1, although serum IgG and T cell responses were similar. At the inoculation dose of 5.0 × 10(6) PFU, rVSV-HSP70-VP1 stimulated significantly higher T cell, fecal, and vaginal IgA responses than rVSV-VP1. Fecal and vaginal IgA responses were also significantly increased when combined vaccination of rVSV-VP1 and rVSV-HSP70 was used. Collectively, these data indicate that (i) insertion of an additional gene (HSP70 or Luc) into the rVSV-VP1 backbone further attenuates the VSV-based vaccine in vitro and in vivo, thus improving the safety of the vaccine candidate, and (ii) HSP70 enhances the human NoV-specific mucosal and T cell immunities triggered by a VSV-based human NoV vaccine. IMPORTANCE Human norovirus (NoV) is responsible for more than 95% of acute nonbacterial gastroenteritis worldwide. Currently, there is no vaccine for this virus. Development of a live attenuated vaccine for human NoV has not been possible because it is uncultivable. Thus, a live vector-based vaccine may provide an alternative vaccine strategy. In this study, we developed a vesicular stomatitis virus (VSV)-based human NoV vaccine candidate. We constructed rVSV-HSP70-VP1, coexpressing heat shock protein (HSP70) and capsid (VP1) genes of human NoV, and rVSV-Luc-VP1, coexpressing firefly luciferase (Luc) and VP1 genes. We found that VSVs with a double gene insertion were significantly more attenuated than VSV with a single VP1 insertion (rVSV-VP1). Furthermore, we found that coexpression or coadministration of HSP70 from VSV vector significantly enhanced human NoV-specific mucosal immunity. Collectively, we developed an improved live vectored vaccine candidate for human NoV which will be useful for future clinical studies.",,"['Ma, Yuanmei', 'Duan, Yue', 'Wei, Yongwei', 'Liang, Xueya', 'Niewiesk, Stefan', 'Oglesbee, Michael', 'Li, Jianrong']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00687-14,PMC3993808,,,,,,,,,
,PMC,Identification and Characterization of a Proteolytically Primed Form of the Murine Coronavirus Spike Proteins after Fusion with the Target Cell,http://dx.doi.org/10.1128/JVI.03451-13,PMC3993802,,,"Enveloped viruses carry highly specialized glycoproteins that catalyze membrane fusion under strict spatial and temporal control. To prevent premature activation after biosynthesis, viral class I fusion proteins adopt a locked conformation and require proteolytic cleavage to render them fusion-ready. This priming step may occur during virus exit from the infected cell, in the extracellular milieu or during entry at or in the next target cell. Proteolytic processing of coronavirus spike (S) fusion proteins during virus entry has been suggested but not yet formally demonstrated, while the nature and functionality of the resulting subunit is still unclear. We used a prototype coronavirus—mouse hepatitis virus (MHV)—to develop a conditional biotinylation assay that enables the specific identification and biochemical characterization of viral S proteins on virions that mediated membrane fusion with the target cell. We demonstrate that MHV S proteins are indeed cleaved upon virus endocytosis, and we identify a novel processing product S2* with characteristics of a fusion-active subunit. The precise cleavage site and the enzymes involved remain to be elucidated. IMPORTANCE Virus entry determines the tropism and is a crucial step in the virus life cycle. We developed an approach to characterize structural components of virus particles after entering new target cells. A prototype coronavirus was used to illustrate how the virus fusion machinery can be controlled.",,"['Wicht, Oliver', 'Burkard, Christine', 'de Haan, Cornelis A. M.', 'van Kuppeveld, Frank J. M.', 'Rottier, Peter J. M.', 'Bosch, Berend Jan']",,,,
,PMC,"Development of an Adenovirus-Based Respiratory Syncytial Virus Vaccine: Preclinical Evaluation of Efficacy, Immunogenicity, and Enhanced Disease in a Cotton Rat Model",http://dx.doi.org/10.1128/JVI.03194-13,PMC3993798,,,"The lack of a vaccine against respiratory syncytial virus (RSV) is a challenging and serious gap in preventive medicine. Herein, we characterize the immunogenicity of an adenovirus serotype 5-based RSV vaccine encoding the fusion (F) protein (Ad5.RSV-F) and the protection provided following immunization with Ad5.RSV-F and assess its potential for producing enhanced disease in a cotton rat (CR) model. Animals were immunized intranasally (i.n.) and/or intramuscularly (i.m.) and subsequently challenged with RSV/A/Tracy (i.n.) to assess protection. Robust immune responses were seen in CRs vaccinated with Ad5.RSV-F given i.m. or i.n., and these responses correlated with reduced replication of the virus in noses and lungs after challenge. Neutralizing antibody responses following immunization with a single dose of Ad5.RSV-F at 1 × 10(11) viral particles (v.p.) elicited antibody titers 64- to 256-fold greater than those seen after natural infection. CRs boosted with Ad5.RSV-F i.n. 28 days after an i.m. dose also had significant increases in neutralizing antibody titers. Antibody affinity for different F-protein antigenic sites revealed substantial differences between antibodies elicited by Ad5.RSV-F and those seen after RSV infection; differences in antibody profiles were also seen between CRs given Ad5.RSV-F i.m. and CRs given Ad5.RSV-F i.n. Ad5.RSV-F priming did not result in enhanced disease following live-virus challenge, in contrast to the histopathology seen in CRs given the formalin-inactivated RSV/A/Burnett vaccine. IMPORTANCE Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in infants and young children and a serious health threat in the immunocompromised and the elderly. Infection severity increased in children in an immunization trial, hampering the over 4-decade-long quest for a successful RSV vaccine. In this study, we show that a genetically engineered RSV-F-encoding adenoviral vector provides protective immunity against RSV challenge without enhanced lung disease in cotton rats (CRs). CRs were vaccinated under a number of different regimens, and the immunity induced by the recombinant adenoviral RSV vaccine administered by use of an intramuscular prime-intranasal boost regimen may provide the best protection for young infants and children at risk of RSV infection, since this population is naive to adenoviral preformed immunity. Overall, this report describes a potential RSV vaccine candidate that merits further evaluation in a phase I clinical study in humans.",,"['Kim, Eun', 'Okada, Kaori', 'Beeler, Judy A.', 'Crim, Roberta L.', 'Piedra, Pedro A.', 'Gilbert, Brian E.', 'Gambotto, Andrea']",,,,
,PMC,Receptor Variation and Susceptibility to Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/JVI.00161-14,PMC3993797,,,"The Middle East respiratory syndrome coronavirus (MERS-CoV) recently spread from an animal reservoir to infect humans, causing sporadic severe and frequently fatal respiratory disease. Appropriate public health and control measures will require discovery of the zoonotic MERS coronavirus reservoirs. The relevant animal hosts are liable to be those that offer optimal MERS virus cell entry. Cell entry begins with virus spike (S) protein binding to DPP4 receptors. We constructed chimeric DPP4 receptors that have the virus-binding domains of indigenous Middle Eastern animals and assessed the activities of these receptors in supporting S protein binding and virus entry. Human, camel, and horse receptors were potent and nearly equally effective MERS virus receptors, while goat and bat receptors were considerably less effective. These patterns reflected S protein affinities for the receptors. However, even the low-affinity receptors could hypersensitize cells to infection when an S-cleaving protease(s) was present, indicating that affinity thresholds for virus entry must be considered in the context of host-cell proteolytic environments. These findings suggest that virus receptors and S protein-cleaving proteases combine in a variety of animals to offer efficient virus entry and that several Middle Eastern animals are potential reservoirs for transmitting MERS-CoV to humans. IMPORTANCE MERS is a frequently fatal disease that is caused by a zoonotic CoV. The animals transmitting MERS-CoV to humans are not yet known. Infection by MERS-CoV requires receptors and proteases on host cells. We compared the receptors of humans and Middle Eastern animals and found that human, camel, and horse receptors sensitized cells to MERS-CoV infection more robustly than goat and bat receptors. Infection susceptibility correlated with affinities of the receptors for viral spike proteins. We also found that the presence of a cell surface lung protease greatly increases susceptibility to MERS-CoV, particularly in conjunction with low-affinity receptors. This cataloguing of human and animal host cell factors allows one to make inferences on the distribution of MERS-CoV in nature.",,"['Barlan, Arlene', 'Zhao, Jincun', 'Sarkar, Mayukh K.', 'Li, Kun', 'McCray, Paul B.', 'Perlman, Stanley', 'Gallagher, Tom']",,,,
,PMC,Ultrastructural Characterization and Three-Dimensional Architecture of Replication Sites in Dengue Virus-Infected Mosquito Cells,http://dx.doi.org/10.1128/JVI.00118-14,PMC3993787,,,"During dengue virus infection of host cells, intracellular membranes are rearranged into distinct subcellular structures such as double-membrane vesicles, convoluted membranes, and tubular structures. Recent electron tomographic studies have provided a detailed three-dimensional architecture of the double-membrane vesicles, representing the sites of dengue virus replication, but temporal and spatial evidence linking membrane morphogenesis with viral RNA synthesis is lacking. Integrating techniques in electron tomography and molecular virology, we defined an early period in virus-infected mosquito cells during which the formation of a virus-modified membrane structure, the double-membrane vesicle, is proportional to the rate of viral RNA synthesis. Convoluted membranes were absent in dengue virus-infected C6/36 cells. Electron tomographic reconstructions elucidated a high-resolution view of the replication complexes inside vesicles and allowed us to identify distinct pathways of particle formation. Hence, our findings extend the structural details of dengue virus replication within mosquito cells and highlight their differences from mammalian cells. IMPORTANCE Dengue virus induces several distinct intracellular membrane structures within the endoplasmic reticulum of mammalian cells. These structures, including double-membrane vesicles and convoluted membranes, are linked, respectively, with viral replication and viral protein processing. However, dengue virus cycles between two disparate animal groups with differing physiologies: mammals and mosquitoes. Using techniques in electron microscopy, we examined the differences between intracellular structures induced by dengue virus in mosquito cells. Additionally, we utilized techniques in molecular virology to temporally link events in virus replication to the formation of these dengue virus-induced membrane structures.",,"['Junjhon, Jiraphan', 'Pennington, Janice G.', 'Edwards, Thomas J.', 'Perera, Rushika', 'Lanman, Jason', 'Kuhn, Richard J.']",,,,
,PMC,MERS-CoV: Bridging the Knowledge Gaps,http://dx.doi.org/10.5001/omj.2014.43,PMC4052384,,,,,"['Balkhair, Abdullah', 'Alawi, Fatma Ba', 'Al Maamari, Khuloud', 'Al Muharrmi, Zakaria', 'Ahmed, Osama']",,,,
,PMC,Highly conserved RNA pseudoknots at the gag-pol junction of HIV-1 suggest a novel mechanism of −1 ribosomal frameshifting,http://dx.doi.org/10.1261/rna.042457.113,PMC3988561,,,"−1 programmed ribosomal frameshifting (PRF) is utilized by many viruses to synthesize their enzymatic (Pol) and structural (Gag) proteins at a defined ratio. For efficient −1 PRF, two cis-acting elements are required: a heptanucleotide frameshift site and a downstream stimulator such as a pseudoknot. We have analyzed the gag-pol junction sequences from 4254 HIV-1 strains. Approximately ninety-five percent of the sequences can form four pseudoknots PK1–PK4 (∼97% contain PK1, PK3, and PK4), covering ∼72 nt including the frameshift site. Some pseudoknots are mutually excluded due to sequence overlap. PK1 and PK3 arrange tandemly. Their stems form a quasi-continuous helix of ∼22 bp. We propose a novel mechanism for possible roles of these pseudoknots. Multiple alternative structures may exist at the gag-pol junction. In most strains, the PK1–PK3 tandem pseudoknots may dominate the structurally heterogeneous pool of RNA due to their greater overall stability. The tandem pseudoknots may function as a breaking system to slow down the ribosome. The ribosome unwinds PK1 and stem 1 of PK3 before it can reach the frameshift site. Then, PK4 can form rapidly because the intact stem 2 of PK3 makes up a large part of the stem 1 of PK4. The newly formed PK4 jams the entrance of the mRNA tunnel. The process then proceeds as in a typical case of −1 PRF. This mechanism incorporates several exquisite new features while still being consistent with the current paradigm of pseudoknot-dependent −1 PRF.",,"['Huang, Xiaolan', 'Yang, Yang', 'Wang, Guan', 'Cheng, Qiang', 'Du, Zhihua']",,,,
,PMC,Assembling evidence for identifying reservoirs of infection,http://dx.doi.org/10.1016/j.tree.2014.03.002,PMC4007595,24726345,CC BY,"Many pathogens persist in multihost systems, making the identification of infection reservoirs crucial for devising effective interventions. Here, we present a conceptual framework for classifying patterns of incidence and prevalence, and review recent scientific advances that allow us to study and manage reservoirs simultaneously. We argue that interventions can have a crucial role in enriching our mechanistic understanding of how reservoirs function and should be embedded as quasi-experimental studies in adaptive management frameworks. Single approaches to the study of reservoirs are unlikely to generate conclusive insights whereas the formal integration of data and methodologies, involving interventions, pathogen genetics, and contemporary surveillance techniques, promises to open up new opportunities to advance understanding of complex multihost systems.",2014 May,"['Viana, Mafalda', 'Mancy, Rebecca', 'Biek, Roman', 'Cleaveland, Sarah', 'Cross, Paul C.', 'Lloyd-Smith, James O.', 'Haydon, Daniel T.']",Trends Ecol Evol,,,
,PMC,An interferon-beta promoter reporter assay for high throughput identification of compounds against multiple RNA viruses,http://dx.doi.org/10.1016/j.antiviral.2014.04.010,PMC4143146,,,"Virus infection of host cells is sensed by innate pattern recognition receptors (PRRs) and induces production of type I interferons (IFNs) and other inflammatory cytokines. These cytokines orchestrate the elimination of the viruses but are occasionally detrimental to the hosts. The outcomes and pathogenesis of viral infection are largely determined by the specific interaction between the viruses and their host cells. Therefore, compounds that either inhibit viral infection or modulate virus-induced cytokine response should be considered as candidates for managing virus infection. The aim of the study was to identify compounds in both categories, using a single cell-based assay. Our screening platform is a HEK293 cell-based reporter assay where the expression of a firefly luciferase is under the control of a human IFN-β promoter. We have demonstrated that infection of the reporter cell line with a panel of RNA viruses activated the reporter gene expression that correlates quantitatively with the levels of virus replication and progeny virus production, and could be inhibited in a dose-dependent manner by known antiviral compound or inhibitors of PRR signal transduction pathways. Using Dengue virus as an example, a pilot screening of a small molecule library consisting of 26,900 compounds proved the concept that the IFN-β promoter reporter assay can serve as a convenient high throughput screening platform for simultaneous discovery of antiviral and innate immune response modulating compounds. A representative antiviral compound from the pilot screening, 1-(6-ethoxybenzo[d]thiazol-2-yl)-3-(3-methoxyphenyl) urea, was demonstrated to specifically inhibit several viruses belonging to the family of flaviviridae.",,"['Guo, Fang', 'Zhao, Xuesen', 'Gill, Tina', 'Zhou, Yan', 'Campagna, Matthew', 'Wang, Lijuan', 'Liu, Fei', 'Zhang, Pinghu', 'DiPaolo, Laura', 'Du, Yanming', 'Xu, Xiaodong', 'Jiang, Dong', 'Wei, Lai', 'Cuconati, Andrea', 'Block, Timothy M', 'Guo, Ju-Tao', 'Chang, Jinhong']",,,,
,PMC,Natural selection and infectious disease in human populations,http://dx.doi.org/10.1038/nrg3734,PMC4912034,,,"The ancient biological 'arms race' between microbial pathogens and humans has shaped genetic variation in modern populations, and this has important implications for the growing field of medical genomics. As humans migrated throughout the world, populations encountered distinct pathogens, and natural selection increased the prevalence of alleles that are advantageous in the new ecosystems in both host and pathogens. This ancient history now influences human infectious disease susceptibility and microbiome homeostasis, and contributes to common diseases that show geographical disparities, such as autoimmune and metabolic disorders. Using new high-throughput technologies, analytical methods and expanding public data resources, the investigation of natural selection is leading to new insights into the function and dysfunction of human biology.",,"['Karlsson, Elinor K.', 'Kwiatkowski, Dominic P.', 'Sabeti, Pardis C.']",,,,
,PMC,Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution,http://dx.doi.org/10.1073/pnas.1402074111,PMC4024880,,,"The newly emerging Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes a Severe Acute Respiratory Syndrome-like disease with ∼43% mortality. Given the recent detection of virus in dromedary camels, zoonotic transfer of MERS-CoV to humans is suspected. In addition, little is known about the role of human neutralizing Ab (nAb) pressure as a driving force in MERS-CoV adaptive evolution. Here, we used a well-characterized nonimmune human Ab-phage library and a panning strategy with proteoliposomes and cells to identify seven human nAbs against the receptor-binding domain (RBD) of the MERS-CoV Spike protein. These nAbs bind to three different epitopes in the RBD and human dipeptidyl peptidase 4 (hDPP4) interface with subnanomolar/nanomolar binding affinities and block the binding of MERS-CoV Spike protein with its hDPP4 receptor. Escape mutant assays identified five amino acid residues that are critical for neutralization escape. Despite the close proximity of the three epitopes on the RBD interface, escape from one epitope did not have a major impact on neutralization with Abs directed to a different epitope. Importantly, the majority of escape mutations had negative impacts on hDPP4 receptor binding and viral fitness. To our knowledge, these results provide the first report on human nAbs against MERS-CoV that may contribute to MERS-CoV clearance and evolution. Moreover, in the absence of a licensed vaccine or antiviral for MERS, this panel of nAbs offers the possibility of developing human mAb-based immunotherapy, especially for health-care workers.",,"['Tang, Xian-Chun', 'Agnihothram, Sudhakar S.', 'Jiao, Yongjun', 'Stanhope, Jeremy', 'Graham, Rachel L.', 'Peterson, Eric C.', 'Avnir, Yuval', 'Tallarico, Aimee St. Clair', 'Sheehan, Jared', 'Zhu, Quan', 'Baric, Ralph S.', 'Marasco, Wayne A.']",,,,
,PMC,Current advancements and potential strategies in the development of MERS-CoV vaccines,http://dx.doi.org/10.1586/14760584.2014.912134,PMC4241375,,,"Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), a new member in the lineage C of β-coronavirus (β-CoV). The increased human cases and high mortality rate of MERS-CoV infection make it essential to develop safe and effective vaccines. In this review, the current advancements and potential strategies in the development of MERS vaccines, particularly subunit vaccines based on MERS-CoV spike (S) protein and its receptor-binding domain (RBD), are discussed. How to improve the efficacy of subunit vaccines through novel adjuvant formulations and routes of administration as well as currently available animal models for evaluating the in vivo efficacy of MERS-CoV vaccines are also addressed. Overall, these strategies may have important implications for the development of effective and safe vaccines for MERS-CoV in the future.",,"['Zhang, Naru', 'Jiang, Shibo', 'Du, Lanying']",,,,
,PMC,Fast vaccine design and development based on correlates of protection (COPs): Influenza as a trendsetter,http://dx.doi.org/10.4161/hv.28639,PMC4186026,,,"New and reemerging infectious diseases call for innovative and efficient control strategies of which fast vaccine design and development represent an important element. In emergency situations, when time is limited, identification and use of correlates of protection (COPs) may play a key role as a strategic tool for accelerated vaccine design, testing, and licensure. We propose that general rules for COP-based vaccine design can be extracted from the existing knowledge of protective immune responses against a large spectrum of relevant viral and bacterial pathogens. Herein, we focus on the applicability of this approach by reviewing the established and up-coming COPs for influenza in the context of traditional and a wide array of new vaccine concepts. The lessons learnt from this field may be applied more generally to COP-based accelerated vaccine design for emerging infections.",,"['van Els, Cécile', 'Mjaaland, Siri', 'Næss, Lisbeth', 'Sarkadi, Julia', 'Gonczol, Eva', 'Smith Korsholm, Karen', 'Hansen, Jon', 'de Jonge, Jørgen', 'Kersten, Gideon', 'Warner, Jennifer', 'Semper, Amanda', 'Kruiswijk, Corine', 'Oftung, Fredrik']",,,,
,PMC,Non-viral adeno-associated virus-based platform for stable expression of antibody combination therapeutics: Non-viral adeno-associated virus-based platform for stable expression of antibody combination therapeutics,http://dx.doi.org/10.4161/mabs.28917,PMC4171029,,,"Antibody combination therapeutics (ACTs) are polyvalent biopharmaceuticals that are uniquely suited for the control of complex diseases, including antibiotic resistant infectious diseases, autoimmune disorders and cancers. However, ACTs also represent a distinct manufacturing challenge because the independent manufacture and subsequent mixing of monoclonal antibodies quickly becomes cost prohibitive as more complex mixtures are envisioned. We have developed a virus-free recombinant protein expression platform based on adeno-associated viral (AAV) elements that is capable of rapid and consistent production of complex antibody mixtures in a single batch format. Using both multiplexed immunoassays and cation exchange (CIEX) chromatography, cell culture supernatants generated using our system were assessed for stability of expression and ratios of the component antibodies over time. Cultures expressing combinations of three to ten antibodies maintained consistent expression levels and stable ratios of component antibodies for at least 60 days. Cultures showed remarkable reproducibility following cell banking, and AAV-based cultures showed higher stability and productivity than non-AAV based cultures. Therefore, this non-viral AAV-based expression platform represents a predictable, reproducible, quick and cost effective method to manufacture or quickly produce for preclinical testing recombinant antibody combination therapies and other recombinant protein mixtures.",,"['Wilmes, Gwendolyn M', 'Carey, Kimberly L', 'Hicks, Stuart W', 'Russell, Hugh H', 'Stevenson, Jesse A', 'Kocjan, Paulina', 'Lutz, Stephen R', 'Quesenberry, Rachel S', 'Shulga-Morskoy, Sergey V', 'Lewis, Megan E', 'Clark, Ethan', 'Medik, Violetta', 'Cooper, Anthony B', 'Reczek, Elizabeth E']",,,,
,PMC,Physical rehabilitation approaches for the recovery of function and mobility following stroke,http://dx.doi.org/10.1002/14651858.CD001920.pub3,PMC6465059,,,"BACKGROUND: Various approaches to physical rehabilitation may be used after stroke, and considerable controversy and debate surround the effectiveness of relative approaches. Some physiotherapists base their treatments on a single approach; others use a mixture of components from several different approaches. OBJECTIVES: To determine whether physical rehabilitation approaches are effective in recovery of function and mobility in people with stroke, and to assess if any one physical rehabilitation approach is more effective than any other approach. For the previous versions of this review, the objective was to explore the effect of 'physiotherapy treatment approaches' based on historical classifications of orthopaedic, neurophysiological or motor learning principles, or on a mixture of these treatment principles. For this update of the review, the objective was to explore the effects of approaches that incorporate individual treatment components, categorised as functional task training, musculoskeletal intervention (active), musculoskeletal intervention (passive), neurophysiological intervention, cardiopulmonary intervention, assistive device or modality. In addition, we sought to explore the impact of time after stroke, geographical location of the study, dose of the intervention, provider of the intervention and treatment components included within an intervention. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched December 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 12, 2012), MEDLINE (1966 to December 2012), EMBASE (1980 to December 2012), AMED (1985 to December 2012) and CINAHL (1982 to December 2012). We searched reference lists and contacted experts and researchers who have an interest in stroke rehabilitation. SELECTION CRITERIA: Randomised controlled trials (RCTs) of physical rehabilitation approaches aimed at promoting the recovery of function or mobility in adult participants with a clinical diagnosis of stroke. Outcomes included measures of independence in activities of daily living (ADL), motor function, balance, gait velocity and length of stay. We included trials comparing physical rehabilitation approaches versus no treatment, usual care or attention control and those comparing different physical rehabilitation approaches. DATA COLLECTION AND ANALYSIS: Two review authors independently categorised identified trials according to the selection criteria, documented their methodological quality and extracted the data. MAIN RESULTS: We included a total of 96 studies (10,401 participants) in this review. More than half of the studies (50/96) were carried out in China. Generally the studies were heterogeneous, and many were poorly reported. Physical rehabilitation was found to have a beneficial effect, as compared with no treatment, on functional recovery after stroke (27 studies, 3423 participants; standardised mean difference (SMD) 0.78, 95% confidence interval (CI) 0.58 to 0.97, for Independence in ADL scales), and this effect was noted to persist beyond the length of the intervention period (nine studies, 540 participants; SMD 0.58, 95% CI 0.11 to 1.04). Subgroup analysis revealed a significant difference based on dose of intervention (P value < 0.0001, for independence in ADL), indicating that a dose of 30 to 60 minutes per day delivered five to seven days per week is effective. This evidence principally arises from studies carried out in China. Subgroup analyses also suggest significant benefit associated with a shorter time since stroke (P value 0.003, for independence in ADL). We found physical rehabilitation to be more effective than usual care or attention control in improving motor function (12 studies, 887 participants; SMD 0.37, 95% CI 0.20 to 0.55), balance (five studies, 246 participants; SMD 0.31, 95% CI 0.05 to 0.56) and gait velocity (14 studies, 1126 participants; SMD 0.46, 95% CI 0.32 to 0.60). Subgroup analysis demonstrated a significant difference based on dose of intervention (P value 0.02 for motor function), indicating that a dose of 30 to 60 minutes delivered five to seven days a week provides significant benefit. Subgroup analyses also suggest significant benefit associated with a shorter time since stroke (P value 0.05, for independence in ADL). No one physical rehabilitation approach was more (or less) effective than any other approach in improving independence in ADL (eight studies, 491 participants; test for subgroup differences: P value 0.71) or motor function (nine studies, 546 participants; test for subgroup differences: P value 0.41). These findings are supported by subgroup analyses carried out for comparisons of intervention versus no treatment or usual care, which identified no significant effects of different treatment components or categories of interventions. AUTHORS' CONCLUSIONS: Physical rehabilitation, comprising a selection of components from different approaches, is effective for recovery of function and mobility after stroke. Evidence related to dose of physical therapy is limited by substantial heterogeneity and does not support robust conclusions. No one approach to physical rehabilitation is any more (or less) effective in promoting recovery of function and mobility after stroke. Therefore, evidence indicates that physical rehabilitation should not be limited to compartmentalised, named approaches, but rather should comprise clearly defined, well‐described, evidenced‐based physical treatments, regardless of historical or philosophical origin.",,"['Pollock, Alex', 'Baer, Gillian', 'Campbell, Pauline', 'Choo, Pei Ling', 'Forster, Anne', 'Morris, Jacqui', 'Pomeroy, Valerie M', 'Langhorne, Peter']",,,,
,PMC,Membrane ectopeptidases targeted by human coronaviruses,http://dx.doi.org/10.1016/j.coviro.2014.03.011,PMC4072739,,,"Six coronaviruses, including the recently identified Middle East respiratory syndrome coronavirus, are known to target the human respiratory tract causing mild to severe disease. Their interaction with receptors expressed on cells located in the respiratory tract is an essential first step in the infection. Thus far three membrane ectopeptidases, dipeptidyl peptidase 4 (DPP4), angiotensin-converting enzyme 2 (ACE2) and aminopeptidase N (APN), have been identified as entry receptors for four human-infecting coronaviruses. Although the catalytic activity of the ACE2, APN, and DPP4 peptidases is not required for virus entry, co-expression of other host proteases allows efficient viral entry. In addition, evolutionary conservation of these receptors may permit interspecies transmissions. Because of the physiological function of these peptidase systems, pathogenic host responses may be potentially amplified and cause acute respiratory distress.",,"['Bosch, Berend Jan', 'Smits, Saskia L.', 'Haagmans, Bart L.']",,,,
,PMC,Daily exercise training protects against albuminuria and angiotensin converting enzyme 2 (ACE2) shedding in db/db diabetic mice,http://dx.doi.org/10.1530/JOE-13-0532,PMC4004628,,,"Angiotensin II (Ang II) is involved in induction and progression of renal damage in diabetes. Angiotensin converting enzyme 2 (ACE2) is highly expressed in the kidney and has been shown to be renoprotective by degrading Ang II to Ang-(1–7). Disintegrin and Metalloproteinase (ADAM) 17 mediated shedding of renal ACE2 contribute to diabetic nephropathy pathogenesis. Lifestyle modification and metformin are recommended as initial therapies for most patients with type 2 diabetes. The aim of the study was to investigate whether exercise training and/or metformin improve glucose homeostasis, albuminuria and downregulate renal ADAM17 and ACE2 shedding in db/db mice. Seven wk old normal and db/db mice were subjected either to sedentary or exercise training with and without metformin (150 mg/kg/day) for 10 wks. Exercise training significantly lowered blood glucose, urinary albumin and ACE2 excretion in db/db mice. ADAM17 and ACE2 proteins were co-localized in cortical tubules of the kidney, suggesting a possible interaction. Metformin treatment was effective in lowering hyperglycemia only during the first 2 weeks of treatment. Increased renal ADAM17 in 17 wk old db/db mice was corrected by physical exercise but not metformin. In addition, exercise training reduced plasma triglycerides and enhanced insulin levels of db/db mice. In conclusion, exercise training alone and in combination with metformin prevented shedding of renal ACE2 by decreasing ADAM17 protein. Urinary ACE2 could serve as a prognostic tool in the progression of kidney damage and its attenuation by exercise may partially contribute to its renal protection.",,"['Somineni, Hari K.', 'Boivin, Gregory P.', 'Elased, Khalid M.']",,,,
,PMC,Issue Information,http://dx.doi.org/10.1002/pro.2347,PMC4005702,,,,,,,,,
,PMC,Interferon induction of IFITM proteins promotes infection by human coronavirus OC43,http://dx.doi.org/10.1073/pnas.1320856111,PMC4020042,,,"IFNs are a family of cytokines that are essential for the antiviral response in vertebrates. Not surprisingly, viruses have adapted to encode virulence factors to cope with the IFN response. Intriguingly, we show here that all three types of interferons, IFN-α, IFN-γ, and IFN-λ, efficiently promote infection by a human coronavirus, HCoV-OC43, one of the major etiological agents of common cold, through the induction of IFN-inducible transmembrane (IFITM) proteins. IFITMs typically exert their antiviral function by inhibiting the entry of a broad spectrum of viruses into their host cells, presumably by trapping and degrading invading virions within the endocytic compartments. In contrast, HCoV-OC43 uses IFN-induced human IFITM2 or IFITM3 as an entry factor to facilitate its infection of host cells. Reverse genetics analyses suggest that the structural motifs critical for the IFITM proteins’ enhancement of HCoV-OC43 infection are distinct from those required for inhibiting infection by other viruses. We also present evidence showing that IFITM family members work as homo- and hetero-oligomers to modulate virus entry. The observed enhancement of HCoV-OC43 infection by IFNs may underlie the propensity of the virus to invade the lower respiratory tract under inflammatory conditions.",,"['Zhao, Xuesen', 'Guo, Fang', 'Liu, Fei', 'Cuconati, Andrea', 'Chang, Jinhong', 'Block, Timothy M.', 'Guo, Ju-Tao']",,,,
,PMC,The Crucial Role of Bile Acids in the Entry of Porcine Enteric Calicivirus,http://dx.doi.org/10.1016/j.virol.2014.04.002,PMC4064365,,,"Replication of porcine enteric calicivirus (PEC) in LLC-PK cells is dependent on the presence of bile acids in the medium. However, the mechanism of bile acid-dependent PEC replication is unknown. Understanding of bile acid-mediated PEC replication may provide insight into cultivating related human noroviruses, currently uncultivable, which are the major cause of viral gastroenteritis outbreaks in humans. Our results demonstrated that while uptake of PEC into the endosomes does not require bile acids, the presence of bile acids is critical for viral escape from the endosomes into cell cytoplasm to initiate viral replication. We also demonstrated that bile acid transporters including the sodium-taurocholate co-transporting polypeptide and the apical sodium-dependent bile acid transporter are important in exerting the effects of bile acids in PEC replication in cells. In summary, our results suggest that bile acids play a critical role in virus entry for successful replication.",,"['Shivanna, Vinay', 'Kim, Yunjeong', 'Chang, Kyeong-Ok']",,,,
,PMC,Lung fibroblasts accelerate wound closure in human alveolar epithelial cells through hepatocyte growth factor/c-Met signaling,http://dx.doi.org/10.1152/ajplung.00233.2013,PMC4080284,,,"There are 190,600 cases of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) each year in the United States, and the incidence and mortality of ALI/ARDS increase dramatically with age. Patients with ALI/ARDS have alveolar epithelial injury, which may be worsened by high-pressure mechanical ventilation. Alveolar type II (ATII) cells are the progenitor cells for the alveolar epithelium and are required to reestablish the alveolar epithelium during the recovery process from ALI/ARDS. Lung fibroblasts (FBs) migrate and proliferate early after lung injury and likely are an important source of growth factors for epithelial repair. However, how lung FBs affect epithelial wound healing in the human adult lung has not been investigated in detail. Hepatocyte growth factor (HGF) is known to be released mainly from FBs and to stimulate both migration and proliferation of primary rat ATII cells. HGF is also increased in lung tissue, bronchoalveolar lavage fluid, and serum in patients with ALI/ARDS. Therefore, we hypothesized that HGF secreted by FBs would enhance wound closure in alveolar epithelial cells (AECs). Wound closure was measured using a scratch wound-healing assay in primary human AEC monolayers and in a coculture system with FBs. We found that wound closure was accelerated by FBs mainly through HGF/c-Met signaling. HGF also restored impaired wound healing in AECs from the elderly subjects and after exposure to cyclic stretch. We conclude that HGF is the critical factor released from FBs to close wounds in human AEC monolayers and suggest that HGF is a potential strategy for hastening alveolar repair in patients with ALI/ARDS.",,"['Ito, Yoko', 'Correll, Kelly', 'Schiel, John A.', 'Finigan, Jay H.', 'Prekeris, Rytis', 'Mason, Robert J.']",,,,
,PMC,Adenovirus Species C Is Associated With Chronic Suppurative Lung Diseases in Children,http://dx.doi.org/10.1093/cid/ciu225,PMC4305137,,,"Background. The role of human adenoviruses (HAdVs) in chronic respiratory disease pathogenesis is recognized. However, no studies have performed molecular sequencing of HAdVs from the lower airways of children with chronic endobronchial suppuration. We thus examined the major HAdV genotypes/species, and relationships to bacterial coinfection, in children with protracted bacterial bronchitis (PBB) and mild bronchiectasis (BE). Methods. Bronchoalveolar lavage (BAL) samples of 245 children with PBB or mild (cylindrical) BE were included in this prospective cohort study. HAdVs were genotyped (when possible) in those whose BAL had HAdV detected (HAdV(+)). Presence of bacterial infection (defined as ≥10(4) colony-forming units/mL) was compared between BAL HAdV(+) and HAdV negative (HAdV(−)) groups. Immune function tests were performed including blood lymphocyte subsets in a random subgroup. Results. Species C HAdVs were identified in 23 of 24 (96%) HAdV(+) children; 13 (57%) were HAdV-1 and 10 (43%) were HAdV-2. An HAdV(+) BAL was significantly associated with bacterial coinfection with Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae (odds ratio [OR], 3.27; 95% confidence interval, 1.38–7.75; P = .007) and negatively associated with Staphylococcus aureus infection (P = .03). Young age was related to increased rates of HAdV(+). Blood CD16 and CD56 natural killer cells were significantly more likely to be elevated in those with HAdV (80%) compared with those without (56.1%) (P = .027). Conclusions. HAdV-C is the major HAdV species detected in the lower airways of children with PBB and BE. Younger age appears to be an important risk factor for HAdV(+) of the lower airways and influences the likelihood of bacterial coinfection.",,"['Wurzel, Danielle F.', 'Mackay, Ian M.', 'Marchant, Julie M.', 'Wang, Claire Y. T.', 'Yerkovich, Stephanie T.', 'Upham, John W.', 'Smith-Vaughan, Heidi C.', 'Petsky, Helen L.', 'Chang, Anne B.']",,,,
,PMC,"Spinal cord injury, immunodepression, and antigenic challenge",http://dx.doi.org/10.1016/j.smim.2014.03.003,PMC5029282,,,The inability to effectively control microbial infection is a leading cause of morbidity and mortality in individuals affected by spinal cord injury (SCI). Available evidence from clinical studies as well as animal models of SCI demonstrate that increased susceptibility to infection is derived from disruption of central nervous system (CNS) communication with the host immune system that ultimately leads to immunodepression. Understanding the molecular and cellular mechanisms governing muted cellular and humoral responses that occur post-injury resulting in impaired host defense following infection is critical for improving the overall quality of life of individuals with SCI. This review focuses on studies performed using preclinical animal models of SCI to evaluate how injury impacts T and B lymphocyte responses following either viral infection or antigenic challenge.,,"['Held, Katherine S.', 'Lane, Thomas E.']",,,,
,PMC,Repurposing staples for viruses: applying peptide design to RSV prophylaxis,http://dx.doi.org/10.1172/JCI75797,PMC4001561,,,"Respiratory syncytial virus (RSV) is responsible for lower respiratory tract infections and annually results in 200,000 deaths worldwide. Despite the burden of RSV-associated disease, treatments and preventative measures are limited. In this issue of JCI, Bird and colleagues describe their work using a peptide stapling technique that allowed synthesis of a stable peptide mimic of a portion of the RSV fusion protein. Pretreatment of cells with the stable peptide effectively blocked virus entry. When introduced into mice prior to RSV exposure, the peptide produced a substantial prophylactic effect. This work provides a new way forward in RSV prevention.",,"['Katen, Sarah P.', 'Dermody, Terence S.']",,,,
,PMC,"Interferon-λ in the Context of Viral Infections: Production, Response and Therapeutic Implications",http://dx.doi.org/10.1159/000360084,PMC6741612,,,"Interferon (IFN)-λ forms the type III IFN family. Although they signal through distinct receptors, type I (IFN-α/β) and type III IFNs elicit remarkably similar responses in cells. However, in vivo, type III and type I IFN responses are not fully redundant as their respective contribution to the antiviral defense highly depends on virus species. IFN-λ is much more potent than IFN-α/β at controlling rotavirus infection. In contrast, clearance of several other viruses, such as influenza virus, mostly depends on IFN-α/β. The IFN-λ receptor was reported to be preferentially expressed on epithelial cells. Cells responsible for IFN-λ production are still poorly characterized but seem to overlap only partly IFN-α/β-producing cells. Accumulating data suggest that epithelial cells are also important IFN-λ producers. Thus, IFN-λ may primarily act as a protection of mucosal entities, such as the lung, skin or digestive tract. Type I and type III IFN signal transduction pathways largely overlap, and cross talk between these IFN systems occurs. Finally, this review addresses the potential benefit of IFN-λ use for therapeutic purposes and summarizes recent results of genome-wide association studies that identified polymorphisms in the region of the IFN-λ3 gene impacting on the outcome of treatments against hepatitis C virus infection.",,"['Hermant, Pascale', 'Michiels, Thomas']",,,,
,PMC,Abstracts from the 37th Annual Meeting of the Society of General Internal Medicine,http://dx.doi.org/10.1007/s11606-014-2834-9,PMC4429500,,,,,,,,,
,PMC,Cancer stem cells: progress and challenges in lung cancer,http://dx.doi.org/10.3978/j.issn.2306-9759.2014.03.06,PMC4923513,,,"The identification of a subpopulation of tumor cells with stem cell-like characteristics first in hematological malignancies and later in solid tumors has emerged into a novel field of cancer research. It has been proposed that this aberrant population of cells now called “cancer stem cells” (CSCs) drives tumor initiation, progression, metastasis, recurrence, and drug resistance. CSCs have been shown to have the capacity of self-renewal and multipotency. Adopting strategies from the field of stem cell research has aided in identification, localization, and targeting of CSCs in many tumors. Despite the huge progress in other solid tumors such as brain, breast, and colon cancers no substantial advancements have been made in lung cancer. This is most likely due to the current rudimentary understanding of lung stem cell hierarchy and heterogeneous nature of lung disease. In this review, we will discuss the most recent findings related to identification of normal lung stem cells and CSCs, pathways involved in regulating the development of CSCs, and the importance of the stem cell niche in development and maintenance of CSCs. Additionally, we will examine the development and feasibility of novel CSC-targeted therapeutic strategies aimed at eradicating lung CSCs.",,"['Templeton, Amanda K.', 'Miyamoto, Shinya', 'Babu, Anish', 'Munshi, Anupama', 'Ramesh, Rajagopal']",,,,
,PMC,Effectiveness of a novel immunogenic nanoparticle platform for Toxoplasma peptide vaccine in HLA transgenic mice,http://dx.doi.org/10.1016/j.vaccine.2014.03.092,PMC4084734,,,"We created and produced a novel self-assembling nanoparticle platform for delivery of peptide epitopes that induces CD8(+) and CD4(+)T cells that are protective against T. gondii infection. These self-assembling polypeptide nanoparticles (SAPNs) are composed of linear peptide (LP) monomers which contain two coiled-coil oligomerization domains, the dense granule 7 (GRA7(20-28) LPQFATAAT) peptide and a universal CD4(+) T cell epitope (derived from PADRE). Purified LPs assemble into nanoparticles with icosahedral symmetry, similar to the capsids of small viruses. These particles were evaluated for their efficacy in eliciting IFN-γ by splenocytes of HLA-B*0702 transgenic mice and for their ability to protect against subsequent T. gondii challenge. This work demonstrates the feasibility of using this platform approach with a CD8(+) epitope that binds HLA-B7 and tests the biological activity of potentially protective peptides restricted by human major histocompatibility complex (HLA) class I molecules in HLA transgenic mice.",,"['Bissati, Kamal El', 'Zhou, Ying', 'Dasgupta, Debleena', 'Cobb, Drew', 'Dubey, Jitender P.', 'Burkhard, Peter', 'Lanar, David E.', 'McLeod, Rima']",,,,
,PMC,Purified coronavirus Spike protein nanoparticles induce coronavirus neutralizing antibodies in mice,http://dx.doi.org/10.1016/j.vaccine.2014.04.016,PMC4058772,,,"Development of vaccination strategies for emerging pathogens are particularly challenging because of the sudden nature of the emergence of these viruses and the long process needed for traditional vaccine development. Therefore, there is a need for development of a rapid method of vaccine development that can respond to emerging pathogens in a short time frame. The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and Middle East respiratory syndrome (MERS-CoV) in late 2012 demonstrate the importance of coronaviruses as emerging pathogens. The spike glycoproteins of coronaviruses reside on the surface of the virion and are responsible for virus entry. The spike glycoprotein is the major immunodominant antigen of coronaviruses and has proven to be an excellent target for vaccine designs that seek to block coronavirus entry and promote antibody targeting of infected cells. Vaccination strategies for coronaviruses have involved live attenuated virus, recombinant viruses, non-replicative virus-like particles expressing coronavirus proteins or DNA plasmids expressing coronavirus genes. None of these strategies has progressed to an approved human coronavirus vaccine in the ten years since SARS-CoV emerged. Here we describe a novel method for generating MERS-CoV and SARS-CoV full-length spike nanoparticles, which in combination with adjuvants are able to produce high titer antibodies in mice.",,"['Coleman, Christopher M', 'Liu, Ye V', 'Mu, Haiyan', 'Taylor, Justin K', 'Massare, Michael', 'Flyer, David C', 'Smith, Gale E', 'Frieman, Matthew B']",,,,
,PMC,Development and evaluation of a one step reverse transcription-loop mediated isothermal amplification assay (RT-LAMP) for rapid detection of foot and mouth disease virus in India,http://dx.doi.org/10.1007/s13337-014-0211-2,PMC4188206,,,"A simple, rapid and sensitive diagnostic assay for Foot-and-mouth disease (FMD) is required for deployment in the field. In this study, development of Reverse Transcription-Loop Mediated Isothermal Amplification (RT-LAMP) assay based on the 3D polymerase gene for specific and rapid detection FMD virus (FMDV) was carried out. The assay was optimised with viral RNA extracted from serotype O, A and Asia 1 FMDV vaccine strains, which resulted a reliable amplification at 65 °C for 60 min. The amplified RT-LAMP products were identified by agarose gel electrophoresis with ethidium bromide staining or observation by naked eye for the presence of turbidity and colour change following the addition of hydroxyl naphthol blue (HNB). The specificity of the assay was demonstrated by the absence of amplification of genome extracted from other viruses or cellular origin. With respect to analytical sensitivity the developed RT-LAMP assay was found more sensitive than routinely used multiplex PCR (mPCR). Further, the assay was evaluated with RNA extracted from cell cultured isolates (n = 50), tongue epithelial samples (n = 150) and semen samples from infected bulls (n = 13). In conclusion, RT-LAMP with HNB dye was shown to be simple, specific and sensitive assay for rapid diagnosis of FMDV infection. Further, the assay has the potential for field deployment and use for rapid FMDV surveillance in India. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13337-014-0211-2) contains supplementary material, which is available to authorized users.",,"['Ranjan, Rajeev', 'Kangayan, Muniswamy', 'Subramaniam, Saravanan', 'Mohapatra, Jajati K.', 'Biswal, Jitendra K.', 'Sharma, Gaurav K.', 'Sanyal, Aniket', 'Pattnaik, Bramhadev']",,,,
,PMC,Infection Prevention in the Emergency Department,http://dx.doi.org/10.1016/j.annemergmed.2014.02.024,PMC4143473,,,"Infection prevention remains a major challenge in emergency care. Acutely ill and injured patients seeking evaluation and treatment in the emergency department (ED) not only have the potential to spread communicable infectious diseases to healthcare personnel and other patients, but are vulnerable to acquiring new infections associated with the care they receive. This article will evaluate these risks and review the existing literature for infection prevention practices in the ED, ranging from hand hygiene, standard and transmission-based precautions, healthcare personnel vaccination, and environmental controls to strategies for preventing healthcare-associated infections. We will conclude by examining what can be done to optimize infection prevention in the ED and identify gaps in knowledge where further research is needed. Successful implementation of evidence-based practices coupled with innovation of novel approaches and technologies tailored specifically to the complex and dynamic environment of the ED are the keys to raising the standard for infection prevention and patient safety in emergency care.",,"['Liang, Stephen Y.', 'Theodoro, Daniel L.', 'Schuur, Jeremiah D.', 'Marschall, Jonas']",,,,
,PMC,Lower Respiratory Tract Virus Findings in Mechanically Ventilated Patients With Severe Community-Acquired Pneumonia,http://dx.doi.org/10.1093/cid/ciu237,PMC4305142,,,"Background. The role of viral infections in the etiology of severe community-acquired pneumonia (SCAP) was prospectively evaluated from 2008 to 2012 at a university-level intensive care unit. Methods. Clinical data and microbiological tests were assessed: blood cultures, urine pneumococcal and legionella antigens, Mycoplasma pneumoniae and Chlamydia pneumoniae antibodies from paired serums, and respiratory virus detection by multiplex, real-time polymerase chain reaction (PCR) from nasopharyngeal swabs and lower tracheal specimens via intubation tube. Results. Of 49 mechanically ventilated SCAP patients (21 men and 28 women; median age, 54 years), the etiology was identified in 45 cases (92%). There were 21 pure bacterial infections (43%), 5 probably pure viral infections (10%), and 19 mixed bacterial–viral infections (39%), resulting in viral etiology in 24 patients (49%). Of 26 viruses, 21 (81%) were detected from bronchial specimens and 5 (19%) from nasopharyngeal swabs. Rhinovirus (15 cases, 58%) and adenovirus (4 cases, 15%) were the most common viral findings. The bacterial–viral etiology group had the highest peak C-reactive protein levels (median, 356 [25th–75th percentiles, 294–416], P = .05), whereas patients with probably viral etiology had the lowest peak procalcitonin levels (1.7 [25th–75th percentiles, 1.6–1.7]). The clinical characteristics of pure bacterial and mixed bacterial–viral etiologies were comparable. Hospital stay was longest among the bacterial group (17 vs 14 days; P = .02). Conclusions. Viral findings were demonstrated in almost half of the SCAP patients. Clinical characteristics were similar between the pure bacterial and mixed bacterial–viral infections groups. The frequency of viral detection depends on the availability of PCR techniques and lower respiratory specimens.",,"['Karhu, J.', 'Ala-Kokko, T. I.', 'Vuorinen, T.', 'Ohtonen, P.', 'Syrjälä, H.']",,,,
,PMC,Neuraminidase inhibitors for preventing and treating influenza in adults and children,http://dx.doi.org/10.1002/14651858.CD008965.pub4,PMC6464969,,,"BACKGROUND: Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide. OBJECTIVES: To describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo‐controlled trials and regulatory comments. SEARCH METHODS: We searched trial registries, electronic databases (to 22 July 2013) and regulatory archives, and corresponded with manufacturers to identify all trials. We also requested clinical study reports. We focused on the primary data sources of manufacturers but we checked that there were no published randomised controlled trials (RCTs) from non‐manufacturer sources by running electronic searches in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE (Ovid), EMBASE, Embase.com, PubMed (not MEDLINE), the Database of Reviews of Effects, the NHS Economic Evaluation Database and the Health Economic Evaluations Database. SELECTION CRITERIA: Randomised, placebo‐controlled trials on adults and children with confirmed or suspected exposure to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: We extracted clinical study reports and assessed risk of bias using purpose‐built instruments. We analysed the effects of zanamivir and oseltamivir on time to first alleviation of symptoms, influenza outcomes, complications, hospitalisations and adverse events in the intention‐to‐treat (ITT) population. All trials were sponsored by the manufacturers. MAIN RESULTS: We obtained 107 clinical study reports from the European Medicines Agency (EMA), GlaxoSmithKline and Roche. We accessed comments by the US Food and Drug Administration (FDA), EMA and Japanese regulator. We included 53 trials in Stage 1 (a judgement of appropriate study design) and 46 in Stage 2 (formal analysis), including 20 oseltamivir (9623 participants) and 26 zanamivir trials (14,628 participants). Inadequate reporting put most of the zanamivir studies and half of the oseltamivir studies at a high risk of selection bias. There were inadequate measures in place to protect 11 studies of oseltamivir from performance bias due to non‐identical presentation of placebo. Attrition bias was high across the oseltamivir studies and there was also evidence of selective reporting for both the zanamivir and oseltamivir studies. The placebo interventions in both sets of trials may have contained active substances. Time to first symptom alleviation. For the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval (CI) 8.4 to 25.1 hours, P < 0.0001). This represents a reduction in the time to first alleviation of symptoms from 7 to 6.3 days. There was no effect in asthmatic children, but in otherwise healthy children there was (reduction by a mean difference of 29 hours, 95% CI 12 to 47 hours, P = 0.001). Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days (95% CI 0.39 to 0.81 days, P < 0.00001), equating to a reduction in the mean duration of symptoms from 6.6 to 6.0 days. The effect in children was not significant. In subgroup analysis we found no evidence of a difference in treatment effect for zanamivir on time to first alleviation of symptoms in adults in the influenza‐infected and non‐influenza‐infected subgroups (P = 0.53). Hospitalisations. Treatment of adults with oseltamivir had no significant effect on hospitalisations: risk difference (RD) 0.15% (95% CI ‐0.78 to 0.91). There was also no significant effect in children or in prophylaxis. Zanamivir hospitalisation data were unreported. Serious influenza complications or those leading to study withdrawal. In adult treatment trials, oseltamivir did not significantly reduce those complications classified as serious or those which led to study withdrawal (RD 0.07%, 95% CI ‐0.78 to 0.44), nor in child treatment trials; neither did zanamivir in the treatment of adults or in prophylaxis. There were insufficient events to compare this outcome for oseltamivir in prophylaxis or zanamivir in the treatment of children. Pneumonia. Oseltamivir significantly reduced self reported, investigator‐mediated, unverified pneumonia (RD 1.00%, 95% CI 0.22 to 1.49); number needed to treat to benefit (NNTB) = 100 (95% CI 67 to 451) in the treated population. The effect was not significant in the five trials that used a more detailed diagnostic form for pneumonia. There were no definitions of pneumonia (or other complications) in any trial. No oseltamivir treatment studies reported effects on radiologically confirmed pneumonia. There was no significant effect on unverified pneumonia in children. There was no significant effect of zanamivir on either self reported or radiologically confirmed pneumonia. In prophylaxis, zanamivir significantly reduced the risk of self reported, investigator‐mediated, unverified pneumonia in adults (RD 0.32%, 95% CI 0.09 to 0.41); NNTB = 311 (95% CI 244 to 1086), but not oseltamivir. Bronchitis, sinusitis and otitis media. Zanamivir significantly reduced the risk of bronchitis in adult treatment trials (RD 1.80%, 95% CI 0.65 to 2.80); NNTB = 56 (36 to 155), but not oseltamivir. Neither NI significantly reduced the risk of otitis media and sinusitis in both adults and children. Harms of treatment. Oseltamivir in the treatment of adults increased the risk of nausea (RD 3.66%, 95% CI 0.90 to 7.39); number needed to treat to harm (NNTH) = 28 (95% CI 14 to 112) and vomiting (RD 4.56%, 95% CI 2.39 to 7.58); NNTH = 22 (14 to 42). The proportion of participants with four‐fold increases in antibody titre was significantly lower in the treated group compared to the control group (RR 0.92, 95% CI 0.86 to 0.97, I(2) statistic = 0%) (5% absolute difference between arms). Oseltamivir significantly decreased the risk of diarrhoea (RD 2.33%, 95% CI 0.14 to 3.81); NNTB = 43 (95% CI 27 to 709) and cardiac events (RD 0.68%, 95% CI 0.04 to 1.0); NNTB = 148 (101 to 2509) compared to placebo during the on‐treatment period. There was a dose‐response effect on psychiatric events in the two oseltamivir ""pivotal"" treatment trials, WV15670 and WV15671, at 150 mg (standard dose) and 300 mg daily (high dose) (P = 0.038). In the treatment of children, oseltamivir induced vomiting (RD 5.34%, 95% CI 1.75 to 10.29); NNTH = 19 (95% CI 10 to 57). There was a significantly lower proportion of children on oseltamivir with a four‐fold increase in antibodies (RR 0.90, 95% CI 0.80 to 1.00, I(2) = 0%). Prophylaxis. In prophylaxis trials, oseltamivir and zanamivir reduced the risk of symptomatic influenza in individuals (oseltamivir: RD 3.05% (95% CI 1.83 to 3.88); NNTB = 33 (26 to 55); zanamivir: RD 1.98% (95% CI 0.98 to 2.54); NNTB = 51 (40 to 103)) and in households (oseltamivir: RD 13.6% (95% CI 9.52 to 15.47); NNTB = 7 (6 to 11); zanamivir: RD 14.84% (95% CI 12.18 to 16.55); NNTB = 7 (7 to 9)). There was no significant effect on asymptomatic influenza (oseltamivir: RR 1.14 (95% CI 0.39 to 3.33); zanamivir: RR 0.97 (95% CI 0.76 to 1.24)). Non‐influenza, influenza‐like illness could not be assessed due to data not being fully reported. In oseltamivir prophylaxis studies, psychiatric adverse events were increased in the combined on‐ and off‐treatment periods (RD 1.06%, 95% CI 0.07 to 2.76); NNTH = 94 (95% CI 36 to 1538) in the study treatment population. Oseltamivir increased the risk of headaches whilst on treatment (RD 3.15%, 95% CI 0.88 to 5.78); NNTH = 32 (95% CI 18 to 115), renal events whilst on treatment (RD 0.67%, 95% CI ‐2.93 to 0.01); NNTH = 150 (NNTH 35 to NNTB > 1000) and nausea whilst on treatment (RD 4.15%, 95% CI 0.86 to 9.51); NNTH = 25 (95% CI 11 to 116). AUTHORS' CONCLUSIONS: Oseltamivir and zanamivir have small, non‐specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children. Using either drug as prophylaxis reduces the risk of developing symptomatic influenza. Treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza (such as pneumonia) are reduced, because of a lack of diagnostic definitions. The use of oseltamivir increases the risk of adverse effects, such as nausea, vomiting, psychiatric effects and renal events in adults and vomiting in children. The lower bioavailability may explain the lower toxicity of zanamivir compared to oseltamivir. The balance between benefits and harms should be considered when making decisions about use of both NIs for either the prophylaxis or treatment of influenza. The influenza virus‐specific mechanism of action proposed by the producers does not fit the clinical evidence.",,"['Jefferson, Tom', 'Jones, Mark A', 'Doshi, Peter', 'Del Mar, Chris B', 'Hama, Rokuro', 'Thompson, Matthew J', 'Spencer, Elizabeth A', 'Onakpoya, Igho J', 'Mahtani, Kamal R', 'Nunan, David', 'Howick, Jeremy', 'Heneghan, Carl J']",,,,
,PMC,Systems kinomics for characterizing host responses to high-consequence pathogens at the NIH/NIAID Integrated Research Facility-Frederick,http://dx.doi.org/10.1111/2049-632X.12163,PMC6136422,,,"Currently, there is a paucity of information regarding the molecular pathogenesis for many high-consequence pathogens (HCPs) that pose threats to both national and international public health. In spite of this, investigations of the molecular pathogenesis for many HCPs have been limited to gross pathological changes in animal models or global analysis of gene expression. Further, questions remain regarding the ability of animal models of disease to recapitulate human molecular pathogenesis or act as predictors of therapeutic efficacy. Thus, it is likely that medical countermeasure development for HCPs will rely on identifying therapeutic targets that are uniquely modulated during HCP infection. It is also appreciated that many cellular processes can be regulated independently of changes in transcription or translation through phosphorylation events. Cellular kinases, individually or collectively (the kinome), play critical roles in regulating complex biology, underlie various malignancies, and represent high-priority drug targets. The growing interest in kinases in both basic and translational research has driven efforts to develop technologies that enable characterization of phosphorylation-mediated signal transduction. To this end, enhanced technical capabilities at the IRF-Frederick provide the unique capability for characterizing host responses to HCP insult during the course of infection and identify novel targets for therapeutic intervention.",,"['Kindrachuk, Jason', 'Falcinelli, Shane', 'Wada, Jiro', 'Kuhn, Jens H.', 'Hensley, Lisa E.', 'Jahrling, Peter B.']",,,,
,PMC,The emergence of the Middle East Respiratory Syndrome coronavirus (MERS-CoV),http://dx.doi.org/10.1111/2049-632X.12166,PMC4106996,,,"On September 20, 2012, a Saudi Arabian physician reported the isolation of a novel coronavirus from a patient with pneumonia on ProMED-mail. Within a few days the same virus was detected in a Qatari patient receiving intensive care in a London hospital, a situation reminiscent of the role air travel played in the spread of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2002. SARS-CoV originated in China’s Guangdong Province and affected more than 8000 patients in 26 countries before it was contained six months later. Over a year after the emergence of this novel coronavirus—Middle East Respiratory Syndrome coronavirus (MERS-CoV)—it has caused 178 laboratory confirmed cases and 76 deaths The emergence of a second highly pathogenic coronavirus within a decade highlights the importance of a coordinated global response incorporating reservoir surveillance, high-containment capacity with fundamental and applied research programs, and dependable communication pathways to ensure outbreak containment. Here we review the current state of knowledge on the epidemiology, ecology, molecular biology, clinical features and intervention strategies of the novel coronavirus, MERS-CoV.",,"['Milne-Price, Shauna', 'Miazgowicz, Kerri L.', 'Munster, Vincent J.']",,,,
,PMC,RSV-encoded NS2 promotes epithelial cell shedding and distal airway obstruction,http://dx.doi.org/10.1172/JCI72948,PMC4001550,,,"Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in young children. The factors that contribute to the increased propensity of RSV-induced distal airway disease compared with other commonly encountered respiratory viruses remain unclear. Here, we identified the RSV-encoded nonstructural 2 (NS2) protein as a viral genetic determinant for initiating RSV-induced distal airway obstruction. Infection of human cartilaginous airway epithelium (HAE) and a hamster model of disease with recombinant respiratory viruses revealed that NS2 promotes shedding of infected epithelial cells, resulting in two consequences of virus infection. First, epithelial cell shedding accelerated the reduction of virus titers, presumably by clearing virus-infected cells from airway mucosa. Second, epithelial cells shedding into the narrow-diameter bronchiolar airway lumens resulted in rapid accumulation of detached, pleomorphic epithelial cells, leading to acute distal airway obstruction. Together, these data indicate that RSV infection of the airway epithelium, via the action of NS2, promotes epithelial cell shedding, which not only accelerates viral clearance but also contributes to acute obstruction of the distal airways. Our results identify RSV NS2 as a contributing factor for the enhanced propensity of RSV to cause severe airway disease in young children and suggest NS2 as a potential therapeutic target for reducing the severity of distal airway disease.",,"['Liesman, Rachael M.', 'Buchholz, Ursula J.', 'Luongo, Cindy L.', 'Yang, Lijuan', 'Proia, Alan D.', 'DeVincenzo, John P.', 'Collins, Peter L.', 'Pickles, Raymond J.']",,,,
,PMC,Interferon-stimulated genes: roles in viral pathogenesis,http://dx.doi.org/10.1016/j.coviro.2014.03.006,PMC4077717,,,"Interferon-stimulated genes (ISGs) are critical for controlling virus infections. As new antiviral ISGs continue to be identified and characterized, their roles in viral pathogenesis are also being explored in more detail. Our current understanding of how ISGs impact viral pathogenesis comes largely from studies in knockout mice, with isolated examples from human clinical data. This review outlines recent developments on the contributions of various ISGs to viral disease outcomes in vivo.",,"Schoggins, John W.",,,,
,PMC,The personal touch: strategies toward personalized vaccines and predicting immune responses to them,http://dx.doi.org/10.1586/14760584.2014.905744,PMC4073206,,,"The impact of vaccines on public health and well-being has been profound. Smallpox has been eradicated, polio is nearing eradication, and multiple diseases have been eliminated from certain areas of the world. Unfortunately, we now face diseases such as: hepatitis C, malaria, or tuberculosis, as well as new and re-emerging pathogens for which lack effective vaccines. Empirical approaches to vaccine development have been successful in the past, but may not be up to the current infectious disease challenges facing us. New, directed approaches to vaccine design, development, and testing need to be developed. Ideally these approaches will capitalize on cutting-edge technologies, advanced analytical and modeling strategies, and up-to-date knowledge of both pathogen and host. These approaches will pay particular attention to the causes of inter-individual variation in vaccine response in order to develop new vaccines tailored to the unique needs of individuals and communities within the population.",,"['Kennedy, Richard B.', 'Ovsyannikova, Inna G.', 'Lambert, Nathaniel D.', 'Haralambieva, Iana H.', 'Poland, Gregory A.']",,,,
,PMC,The three lives of viral fusion peptides,http://dx.doi.org/10.1016/j.chemphyslip.2014.03.003,PMC4061400,,,"Fusion peptides comprise conserved hydrophobic domains absolutely required for the fusogenic activity of glycoproteins from divergent virus families. After 30 years of intensive research efforts, the structures and functions underlying their high degree of sequence conservation are not fully elucidated. The long-hydrophobic viral fusion peptide (VFP) sequences are structurally constrained to access three successive states after biogenesis. Firstly, the VFP sequence must fulfill the set of native interactions required for (meta) stable folding within the globular ectodomains of glycoprotein complexes. Secondly, at the onset of the fusion process, they get transferred into the target cell membrane and adopt specific conformations therein. According to commonly accepted mechanistic models, membrane-bound states of the VFP might promote the lipid bilayer remodeling required for virus-cell membrane merger. Finally, at least in some instances, several VFPs co-assemble with transmembrane anchors into membrane integral helical bundles, following a locking movement hypothetically coupled to fusion-pore expansion. Here we review different aspects of the three major states of the VFPs, including the functional assistance by other membrane-transferring glycoprotein regions, and discuss briefly their potential as targets for clinical intervention.",,"['Apellániz, Beatriz', 'Huarte, Nerea', 'Largo, Eneko', 'Nieva, José L.']",,,,
,PMC,Critically Ill Patients With Influenza A(H1N1)pdm09 Virus Infection in 2014,http://dx.doi.org/10.1001/jama.2014.2116,PMC6689404,,,,,"['Napolitano, Lena M.', 'Angus, Derek C.', 'Uyeki, Timothy M.']",,,,
,PMC,A Rapid Needs Assessment of the Rockaway Peninsula in New York City After Hurricane Sandy and the Relationship of Socioeconomic Status to Recovery,http://dx.doi.org/10.2105/AJPH.2013.301668,PMC4025720,,,"Objectives. We conducted a rapid needs assessment in the Rockaway Peninsula—one of the areas of New York City most severely affected by Hurricane Sandy on October 29, 2012—to assess basic needs and evaluate for an association between socioeconomic status (SES) and storm recovery. Methods. We conducted a cross-sectional survey within the Rockaways 3 weeks after the hurricane made landfall to elicit information regarding basic utilities, food access, health, relief-effort opinions, and SES. We used a modified cluster sampling method to select households with a goal of 7 to 10 surveys per cluster. Results. Thirty to fifty percent of households were without basic utilities including electricity, heat, and telephone services. Lower-income households were more likely to worry about food than higher-income households (odds ratio = 4.5; 95% confidence interval = 1.43, 15.23; P = .01). A post-storm trend also existed among the lower-income group towards psychological disturbances. Conclusions. Storm preparation should include disseminating information regarding carbon monoxide and proper generator use, considerations for prescription refills, neighborhood security, and location of food distribution centers. Lower-income individuals may have greater difficulty meeting their needs following a natural disaster, and recovery efforts may include prioritization of these households.",,"['Subaiya, Saleena', 'Moussavi, Cyrus', 'Velasquez, Anthony', 'Stillman, Joshua']",,,,
,PMC,Tertiary Lymphoid Structures Target the Antitumor Immune Response to Lung Cancer,http://dx.doi.org/10.1164/rccm.201402-0317ED,PMC4225836,,,,,"['Randall, Troy D.', 'Kern, Jeffrey A.']",,,,
,PMC,Knowledge and attitude of healthcare workers and patients on healthcare associated infections in a regional hospital in Ghana,http://dx.doi.org/10.1016/S2222-1808(14)60330-3,PMC4032042,,,"OBJECTIVE: To assess knowledge and attitude of healthcare workers (HCWs) and patients on healthcare associated infections (HAIs) in the central regional hospital in Ghana. METHODS: The purposive random sampling method was used to administer questionnaires over a period of 6 months to HCWs and patients visiting the hospital. RESULTS: A total of 210 patients and 71 HCWs were sampled. One hundred and three (53.8%) patients had some knowledge of HAIs with 52 (28.4%) being informed by a HCW compared with 63 (88.7%) of HCWs who were well informed about HAIs. Ninety-seven (46.2%) responding patient always washed their hands while 65 (31%) and 48 (22.9%) respectively sometimes or never washed their hands within or after leaving the hospital. Out of those who washed their hands, 64 (39.5%) always washed with soap while 46 (28.4%) did sometimes. This positively and significantly correlated (r=0.440, P<0.001) with knowledge on HAIs which was however insignificant in HCWs (r=0.025, P=0.835). As many as 48 (67.6%) of HCWs believed that authorities in the hospital had done little to prevent HAIs with the main reason being that the hospital was unclean. Whereas, 112 (53.3%) of patients considered the hospital clean. Twenty-seven (38%) of HCWs had had confirmed HAIs of which cholera made up 12 (16.9%) while 94 (44.8%) of patients believed they had had unconfirmed HAIs. CONCLUSIONS: Although knowledge on HAIs is adequate, low compliance on preventive techniques resulting in high HAIs indicates attitudinal change is the best means of prevention.",,"['Ocran, Irene', 'Tagoe, Daniel Nii Aryee']",,,,
,PMC,A BSL-4 High-Throughput Screen Identifies Sulfonamide Inhibitors of Nipah Virus,http://dx.doi.org/10.1089/adt.2013.567,PMC3994909,,,"Nipah virus is a biosafety level 4 (BSL-4) pathogen that causes severe respiratory illness and encephalitis in humans. To identify novel small molecules that target Nipah virus replication as potential therapeutics, Southern Research Institute and Galveston National Laboratory jointly developed an automated high-throughput screening platform that is capable of testing 10,000 compounds per day within BSL-4 biocontainment. Using this platform, we screened a 10,080-compound library using a cell-based, high-throughput screen for compounds that inhibited the virus-induced cytopathic effect. From this pilot effort, 23 compounds were identified with EC(50) values ranging from 3.9 to 20.0 μM and selectivities >10. Three sulfonamide compounds with EC(50) values <12 μM were further characterized for their point of intervention in the viral replication cycle and for broad antiviral efficacy. Development of HTS capability under BSL-4 containment changes the paradigm for drug discovery for highly pathogenic agents because this platform can be readily modified to identify prophylactic and postexposure therapeutic candidates against other BSL-4 pathogens, particularly Ebola, Marburg, and Lassa viruses.",,"['Tigabu, Bersabeh', 'Rasmussen, Lynn', 'White, E. Lucile', 'Tower, Nichole', 'Saeed, Mohammad', 'Bukreyev, Alexander', 'Rockx, Barry', 'LeDuc, James W.', 'Noah, James W.']",,,,
,PMC,"Comparison of levels and duration of detection of antibodies to bovine viral diarrhea virus 1, bovine viral diarrhea virus 2, bovine respiratory syncytial virus, bovine herpesvirus 1, and bovine parainfluenza virus 3 in calves fed maternal colostrum or a colostrum-replacement product",,PMC3962282,,,"Colostrum-replacement products are an alternative to provide passive immunity to neonatal calves; however, their ability to provide adequate levels of antibodies recognizing respiratory viruses has not been described. The objective of this study was to compare the serum levels of IgG at 2 d of age and the duration of detection of antibodies to bovine viral diarrhea virus 1 (BVDV-1), bovine viral diarrhea virus 2 (BVDV-2), bovine respiratory syncytial virus (BRSV), bovine herpesvirus 1 (BHV-1), and bovine parainfluenza virus 3 (BPIV-3) in calves fed maternal colostrum (MC) or a colostrum replacement (CR) at birth. Forty newborn male Holstein calves were assigned to the CR or the MC group. Group CR (n = 20) received 2 packets of colostrum replacement (100 g of IgG per 470-g packet), while group MC (n = 20) received 3.8 L of maternal colostrum. Blood samples for detection of IgG and virus antibodies were collected from each calf at birth, at 2 and 7 d, and monthly until the calves became seronegative. Calves in the MC group had greater IgG concentrations at 2 d of age. The apparent efficiency of absorption of IgG was greater in the MC group than in the CR group, although the difference was not significant. Calves in the CR group had greater concentrations of BVDV neutralizing antibodies during the first 4 mo of life. The levels of antibodies to BRSV, BHV-1, and BPIV-3 were similar in the 2 groups. The mean time to seronegativity was similar for each virus in the 2 groups; however, greater variation was observed in the antibody levels and in the duration of detection of immunity in the MC group than in the CR group. Thus, the CR product provided calves with more uniform levels and duration of antibodies to common bovine respiratory viruses.",,"['Chamorro, Manuel F.', 'Walz, Paul H.', 'Haines, Deborah M.', 'Passler, Thomas', 'Earleywine, Thomas', 'Palomares, Roberto A.', 'Riddell, Kay P.', 'Galik, Patricia', 'Zhang, Yijing', 'Givens, M. Daniel']",,,,
,PMC,"A Simple, Quantitative Method Using Alginate Gel to Determine Rat Colonic Tumor Volume In Vivo",,PMC3997291,,,"Many studies of the response of colonic tumors to therapeutics use tumor multiplicity as the endpoint to determine the effectiveness of the agent. These studies can be greatly enhanced by accurate measurements of tumor volume. Here we present a quantitative method to easily and accurately determine colonic tumor volume. This approach uses a biocompatible alginate to create a negative mold of a tumor-bearing colon; this mold is then used to make positive casts of dental stone that replicate the shape of each original tumor. The weight of the dental stone cast correlates highly with the weight of the dissected tumors. After refinement of the technique, overall error in tumor volume was 16.9% ± 7.9% and includes error from both the alginate and dental stone procedures. Because this technique is limited to molding of tumors in the colon, we utilized the Apc(Pirc/+) rat, which has a propensity for developing colonic tumors that reflect the location of the majority of human intestinal tumors. We have successfully used the described method to determine tumor volumes ranging from 4 to 196 mm(3). Alginate molding combined with dental stone casting is a facile method for determining tumor volume in vivo without costly equipment or knowledge of analytic software. This broadly accessible method creates the opportunity to objectively study colonic tumors over time in living animals in conjunction with other experiments and without transferring animals from the facility where they are maintained.",,"['Irving, Amy A', 'Young, Lindsay B', 'Pleiman, Jennifer K', 'Konrath, Michael J', 'Marzella, Blake', 'Nonte, Michael', 'Cacciatore, Justin', 'Ford, Madeline R', 'Clipson, Linda', 'Amos-Landgraf, James M', 'Dove, William F']",,,,
,PMC,Early Life Viral Infections and the Development of Asthma – A Target for Asthma Prevention?,http://dx.doi.org/10.1097/ACI.0000000000000047,PMC4083742,,,"PURPOSE OF THE REVIEW: To discuss recent insights into the relationships between viral respiratory infections and asthma inception in the context of a long-term goal of moving towards prevention strategies for childhood asthma. RECENT FINDINGS: There is strong evidence for respiratory syncytial virus (RSV) and human rhinovirus (RV) wheezing illnesses as important risk factors for asthma inception. The mechanisms underlying these relationships have been an intense area of study. Novel approaches for the prevention of virus infections and/or lessening the severity of associated illnesses are at various stages of development, and are important potential tools in efforts aimed at primary and secondary prevention of asthma. SUMMARY: Viral respiratory infections in early life are a major source of morbidity and critical in the development of asthma. Mechanisms by which these infections lead to asthma inception in susceptible individuals are emerging. Further, there are promising potential interventions currently available that should be tested in clinical trials. The goal of prevention of disease inception is clearly on the horizon.",,"Jackson, Daniel J.",,,,
,PMC,The Lung Microbiome After Lung Transplantation,http://dx.doi.org/10.1586/17476348.2014.890518,PMC4765386,,,"Lung transplantation survival remains significantly impacted by infections and the development of chronic rejection manifesting as bronchiolitis obliterans syndrome (BOS). Traditional microbiologic data has provided insight into the role of infections in BOS. Now, new non-culture-based techniques have been developed to characterize the entire population of microbes resident on the surfaces of the body, also known as the human microbiome. Early studies have identified that lung transplant patients have a different lung microbiome and have demonstrated the important finding that the transplant lung microbiome changes over time. Furthermore, both unique bacterial populations and longitudinal changes in the lung microbiome have now been suggested to play a role in the development of BOS. In the future, this technology will need to be combined with functional assays and assessment of the immune responses in the lung to help further explain the microbiome’s role in the failing lung allograft.",,"['Becker, Julia B.', 'Poroyko, Valeriy', 'Bhorade, Sangeeta']",,,,
,PMC,Insulin Requirements in Non-Critically Ill Hospitalized Patients With Diabetes and Steroid-Induced Hyperglycemia,http://dx.doi.org/10.3810/hp.2014.04.1100,PMC4109974,,,"OBJECTIVE: Steroid-induced hyperglycemia is common in hospitalized patients with diabetes mellitus. Guidelines for glucose management in this setting are lacking. METHODS: We conducted a retrospective chart review of non-critically ill patients with diabetes receiving steroids, hospitalized from January 2009 to October 2012. Fifty-eight patients were identified from 247 consults. Multivariable linear regression was used to assess median daily insulin requirements of normoglycemic patients compared with hyperglycemic patients. RESULTS: Of the 58 total patients included in our study, 20 achieved normoglycemia during admission (patient-day weighted mean blood glucose [PDWMBG] level = 154 ± 16 mg/dL) and 38 remained hyperglycemic (PDWMBG level= 243 ± 39 mg/dL; P < 0.001). There were no differences between the 2 patient groups in age, sex, race, body weight, renal function, HbA(1c) level, glucose-altering medications, diabetes type, or disease duration. Following multivariable adjustment, compared with hyperglycemic patients, normoglycemic patients required similar units of basal insulin (median [interquartile range])(23.6 [17.9, 31.2] vs 20.1 [16.5, 24.4]; P = 0.35); higher units of nutritional insulin (45.5 [34.2, 60.4] vs 20.1 [16.4, 24.5]; P < 0.001]; and lower units of correctional insulin (5.8 [4.1, 8.1] vs 13.0 [10.2, 16.5]; P < 0.001]). Patients achieving normoglycemia required a significantly lower percentage of correction insulin (total daily dose [TDD]: 7.4% vs 23.4%; P < 0.001) and a higher percentage of nutritional insulin (TDD: 58.1% vs 36.2%; P < 0.001) than hyperglycemic patients. There was no difference in the TDD per kilogram, TDD per milligram hydrocortisone dose, or TDD per milligram hydrocortisone dose per kilogram weight between the 2 groups. CONCLUSION: The data suggest that non-critically ill patients with hyperglycemia receiving steroids require a higher percentage of TDD insulin therapy as nutritional insulin to achieve normoglycemia.",,"['Spanakis, Elias K.', 'Shah, Nina', 'Malhotra, Keya', 'Kemmerer, Terri', 'Yeh, Hsin-Chieh', 'Golden, Sherita Hill']",,,,
,PMC,Type I Interferons Promote Severe Disease in a Mouse Model of Lethal Ehrlichiosis,http://dx.doi.org/10.1128/IAI.01564-13,PMC3993392,,,"Human monocytic ehrlichiosis (HME) is caused by a tick-borne obligate intracellular pathogen of the order Rickettsiales. HME disease can range from mild to a fatal, toxic shock-like syndrome, yet the mechanisms regulating pathogenesis are not well understood. We define a central role for type I interferons (alpha interferon [IFN-α] and IFN-β) in severe disease in a mouse model of fatal ehrlichiosis caused by Ixodes ovatus Ehrlichia (IOE). IFN-α and IFN-β were induced by IOE infection but not in response to a less virulent strain, Ehrlichia muris. The major sources of type I IFNs during IOE infection were plasmacytoid dendritic cells and monocytes. Mice lacking the receptor for type I IFNs (Ifnar deficient) or neutralization of IFN-α and IFN-β resulted in a reduced bacterial burden. Ifnar-deficient mice exhibited significantly increased survival after IOE infection, relative to that of wild-type (WT) mice, that correlated with increased type II IFN (IFN-γ) production. Pathogen-specific antibody responses were also elevated in Ifnar-deficient mice, and this required IFN-γ. Remarkably, increased IFN-γ and IgM were not essential for protection in the absence of type I IFN signaling. The direct effect of type I IFNs on hematopoietic and nonhematopoietic cells was evaluated in bone marrow chimeric mice. We observed that chimeric mice containing Ifnar-deficient hematopoietic cells succumbed to infection early, whereas Ifnar-deficient mice containing WT hematopoietic cells exhibited increased survival, despite having a higher bacterial burden. These data demonstrate that IFN-α receptor signaling in nonhematopoietic cells is important for pathogenesis. Thus, type I IFNs are induced during a rickettsial infection in vivo and promote severe disease.",,"['Zhang, Yubin', 'Thai, Vinh', 'McCabe, Amanda', 'Jones, Maura', 'MacNamara, Katherine C.']",,,,
,PMC,Tools for Detection of Mycoplasma amphoriforme: a Primary Respiratory Pathogen?,http://dx.doi.org/10.1128/JCM.03049-13,PMC3993489,,,"Mycoplasma amphoriforme is a recently described organism isolated from the respiratory tracts of patients with immunodeficiency and evidence of chronic infection. Novel assays for the molecular detection of the organism by real-time quantitative PCRs (qPCRs) targeting the uracil DNA glycosylase gene (udg) or the 23S rRNA gene are described here. The analytical sensitivities are similar to the existing conventional M. amphoriforme 16S rRNA gene PCR, with the advantage of being species specific, rapid, and quantitative. By using these techniques, we demonstrate the presence of this organism in 17 (19.3%) primary antibody-deficient (PAD) patients, 4 (5%) adults with lower respiratory tract infection, 1 (2.6%) sputum sample from a patient attending a chest clinic, and 23 (0.21%) samples submitted for viral diagnosis of respiratory infection, but not in normal adult control subjects. These data show the presence of this microorganism in respiratory patients and suggest that M. amphoriforme may infect both immunocompetent and immunocompromised people. Further studies to characterize this organism are required, and this report provides the tools that may be used by other research groups to investigate its pathogenic potential.",,"['Ling, Clare L.', 'Oravcova, Katarina', 'Beattie, Thomas F.', 'Creer, Dean D.', 'Dilworth, Paul', 'Fulton, Naomi L.', 'Hardie, Alison', 'Munro, Michelle', 'Pond, Marcus', 'Templeton, Kate', 'Webster, David', 'Workman, Sarita', 'McHugh, Timothy D.', 'Gillespie, Stephen H.']",,,,
,PMC,The Value of Postmortem Microbiology Cultures,http://dx.doi.org/10.1128/JCM.03102-13,PMC3993482,,,"Since the inception of evidence-based scientific concepts in medicine in the 19th century, the utility of postmortem microbiologic examinations has been a topic of controversy. For every study describing a lack of correlation between antemortem clinical and laboratory findings and postmortem culture results, there is equal evidence from other studies that indicates at least some limited utility in select cases. While the contributions of autopsies and postmortem microbiologic examinations in the discovery of novel infectious microorganisms are generally appreciated by the medical and scientific societies, the problems of implementing routine procedures in daily autopsy practice clearly relate to the lack of consensus on their broader utility as well as to a lack of regulatory guidelines. This review provides an overview of the literature-based evidence regarding the utility of postmortem microbiologic examinations together with some practical aspects and guidelines for those confronted with the issue of whether to allow or discourage the use of bacteriologic cultures obtained during autopsies.",,"Riedel, Stefan",,,,
,PMC,Cyclovirus in nasopharyngeal aspirates of Chilean children with respiratory infections,http://dx.doi.org/10.1099/vir.0.061143-0,PMC3973479,,,"Some respiratory tract infections remain unexplained despite extensive testing for common pathogens. Nasopharyngeal aspirates (NPAs) from 120 Chilean infants from Santiago with acute lower respiratory tract infections were analysed by viral metagenomics, revealing the presence of nucleic acids from anelloviruses, adenovirus-associated virus and 12 known respiratory viral pathogens. A single sequence read showed translated protein similarity to cycloviruses. We used inverse PCR to amplify the complete circular ssDNA genome of a novel cyclovirus we named CyCV-ChileNPA1. Closely related variants were detected using PCR in the NPAs of three other affected children that also contained anelloviruses. This report increases the current knowledge of the genetic diversity of cycloviruses whose detection in multiple NPAs may reflect a tropism for human respiratory tissues.",,"['Phan, Tung Gia', 'Luchsinger, Vivian', 'Avendaño, Luis F.', 'Deng, Xutao', 'Delwart, Eric']",,,,
,PMC,The ORF4b-encoded accessory proteins of Middle East respiratory syndrome coronavirus and two related bat coronaviruses localize to the nucleus and inhibit innate immune signalling,http://dx.doi.org/10.1099/vir.0.062059-0,PMC3973478,,,"The recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV), a betacoronavirus, is associated with severe pneumonia and renal failure. The environmental origin of MERS-CoV is as yet unknown; however, its genome sequence is closely related to those of two bat coronaviruses, named BtCoV-HKU4 and BtCoV-HKU5, which were derived from Chinese bat samples. A hallmark of highly pathogenic respiratory viruses is their ability to evade the innate immune response of the host. CoV accessory proteins, for example those from severe acute respiratory syndrome CoV (SARS-CoV), have been shown to block innate antiviral signalling pathways. MERS-CoV, similar to SARS-CoV, has been shown to inhibit type I IFN induction in a variety of cell types in vitro. We therefore hypothesized that MERS-CoV and the phylogenetically related BtCoV-HKU4 and BtCoV-HKU5 may encode proteins with similar capabilities. In this study, we have demonstrated that the ORF4b-encoded accessory protein (p4b) of MERS-CoV, BtCoV-HKU4 and BtCoV-HKU5 may indeed facilitate innate immune evasion by inhibiting the type I IFN and NF-κB signalling pathways. We also analysed the subcellular localization of p4b from MERS-CoV, BtCoV-HKU4 and BtCoV-HKU5 and demonstrated that all are localized to the nucleus.",,"['Matthews, Krystal L.', 'Coleman, Christopher M.', 'van der Meer, Yvonne', 'Snijder, Eric J.', 'Frieman, Matthew B.']",,,,
,PMC,"Isolation, propagation, genome analysis and epidemiology of HKU1 betacoronaviruses",http://dx.doi.org/10.1099/vir.0.059832-0,PMC3973476,,,"From 1 January 2009 to 31 May 2013, 15 287 respiratory specimens submitted to the Clinical Virology Laboratory at the Children’s Hospital Colorado were tested for human coronavirus RNA by reverse transcription-PCR. Human coronaviruses HKU1, OC43, 229E and NL63 co-circulated during each of the respiratory seasons but with significant year-to-year variability, and cumulatively accounted for 7.4–15.6 % of all samples tested during the months of peak activity. A total of 79 (0.5 % prevalence) specimens were positive for human betacoronavirus HKU1 RNA. Genotypes HKU1 A and B were both isolated from clinical specimens and propagated on primary human tracheal–bronchial epithelial cells cultured at the air–liquid interface and were neutralized in vitro by human intravenous immunoglobulin and by polyclonal rabbit antibodies to the spike glycoprotein of HKU1. Phylogenetic analysis of the deduced amino acid sequences of seven full-length genomes of Colorado HKU1 viruses and the spike glycoproteins from four additional HKU1 viruses from Colorado and three from Brazil demonstrated remarkable conservation of these sequences with genotypes circulating in Hong Kong and France. Within genotype A, all but one of the Colorado HKU1 sequences formed a unique subclade defined by three amino acid substitutions (W197F, F613Y and S752F) in the spike glycoprotein and exhibited a unique signature in the acidic tandem repeat in the N-terminal region of the nsp3 subdomain. Elucidating the function of and mechanisms responsible for the formation of these varying tandem repeats will increase our understanding of the replication process and pathogenicity of HKU1 and potentially of other coronaviruses.",,"['Dominguez, Samuel R.', 'Shrivastava, Susmita', 'Berglund, Andrew', 'Qian, Zhaohui', 'Góes, Luiz Gustavo Bentim', 'Halpin, Rebecca A.', 'Fedorova, Nadia', 'Ransier, Amy', 'Weston, Philip A.', 'Durigon, Edison Luiz', 'Jerez, José Antonio', 'Robinson, Christine C.', 'Town, Christopher D.', 'Holmes, Kathryn V.']",,,,
,PMC,Anti-inflammatory and Antimicrobial Effects of Heat-Clearing Chinese Herbs: A Current Review,http://dx.doi.org/10.4103/2225-4110.126635,PMC4003708,24860732,CC BY-NC-SA,"Inflammation is a normal immune response; but if the body's regulation of inflammation is dysfunctional, then it will have an adverse effect on the body. Although use of modern drugs for inflammation has a relieving effect, it is still unsatisfactory. Moreover, the emergence of drug-resistant strains and even new kinds of microorganisms is causing significant morbidity and mortality. Recently, more attention has been focused on herbal medicine to treat various diseases because of the ability of the herbs to affect multiple target signaling pathways and their multiple mechanisms of action. Thus, a large number of studies have reported on the anti-inflammatory and antimicrobial effects of the traditional Chinese herbs. Literature survey was performed by conducting systematic electronic search in PubMed, Science Direct, Google Scholar, and in books. This review has listed 11 heat-clearing Chinese herbs (HCCHs) including Scutellaria baicalensis (黃芩 Huáng Qín), Coptis chinensis (黃連 Huáng Lián), Flos Lonicerae (金銀花 Jīn Yín Hūa), Forsythia suspensa (連翹 Lián Qiào), Isatidis Folium (大青葉 Dà Qīn Yè), Radix Isatidis (板藍根 Bǎn Lán Gēn), Viola yedoensis (紫花地丁 Zǐ Huā Dì Dīn), Pulsatilla Radix (白頭翁 Bái Tóu Wēn), Andrographis paniculata (穿心蓮 Chuān Xīn Lián), Houttuynia cordata (魚腥草 Yú Xīng Cǎo), and Patrinia Herba (敗醬草 Bài Jiàn Cǎo), which have anti-inflammatory and antimicrobial effects, and has described their effects through different mechanisms of action and multiple targets. Their ability to affect multiple target signaling pathways and their potential mechanisms of action contributing to their anti-inflammatory and antimicrobial activity may be related to their action of removing heat and counteracting toxicity. Further studies are needed on the collection of HCCHs to know the detailed mechanism of action of herbs in this group for the assessment of effective drug.",2014 Apr-Jun,"['Muluye, Rekik A.', 'Bian, Yuhong', 'Alemu, Paulos N.']",J Tradit Complement Med,,,
,PMC,Surfactant-Modified Nanoclay Exhibits an Antiviral Activity with High Potency and Broad Spectrum,http://dx.doi.org/10.1128/JVI.03256-13,PMC3993779,,,"Nanomaterials have the characteristics associated with high surface-to-volume ratios and have been explored for their antiviral activity. Despite some success, cytotoxicity has been an issue in nanomaterial-based antiviral strategies. We previously developed a novel method to fully exfoliate montmorillonite clay to generate the most fundamental units of nanoscale silicate platelet (NSP). We further modified NSP by capping with various surfactants and found that the surfactant-modified NSP (NSQ) was less cytotoxic. In this study, we tested the antiviral potentials of a series of natural-clay-derived nanomaterials. Among the derivatives, NSP modified with anionic sodium dodecyl sulfate (NSQc), but not the pristine clay, unmodified NSP, a silver nanoparticle-NSP hybrid, NSP modified with cationic n-octadecanylamine hydrochloride salt, or NSP modified with nonionic Triton X-100, significantly suppressed the plaque-forming ability of Japanese encephalitis virus (JEV) at noncytotoxic concentrations. NSQc also blocked infection with dengue virus (DEN) and influenza A virus. Regarding the antiviral mechanism, NSQc interfered with viral binding through electrostatic interaction, since its antiviral activity can be neutralized by Polybrene, a cationic polymer. Furthermore, NSQc reduced the lethality of JEV and DEN infection in mouse challenge models. Thus, the surfactant-modified exfoliated nanoclay NSQc may be a novel nanomaterial with broad and potent antiviral activity. IMPORTANCE Nanomaterials have being investigated as antimicrobial agents, yet their antiviral potential is overshadowed by their cytotoxicity. By using a novel method, we fully exfoliated montmorillonite clay to generate the most fundamental units of nanoscale silicate platelet (NSP). Here, we show that the surfactant-modified NSP (NSQ) is less cytotoxic and that NSQc (NSP modified with sodium dodecyl sulfate) could potently block infection by dengue virus (DEN), Japanese encephalitis virus (JEV), and influenza A virus at noncytotoxic concentrations. For the antiviral mechanism, we find that the electrostatic interaction between the negatively charged NSQc and the positively charged virus particles blocks viral binding. Furthermore, we used mouse challenge models of JEV and DEN to demonstrate the in vivo antiviral potential of NSQc. Thus, NSQc may function as a potent and safe antiviral nanohybrid against several viruses, and our success in synthesizing surfactant-modified NSP with antiviral activity may shed some light on future antiviral development.",,"['Liang, Jian-Jong', 'Wei, Jiun-Chiou', 'Lee, Yi-Ling', 'Hsu, Shan-hui', 'Lin, Jiang-Jen', 'Lin, Yi-Ling']",,,,
,PMC,Recognition of the Murine Coronavirus Genomic RNA Packaging Signal Depends on the Second RNA-Binding Domain of the Nucleocapsid Protein,http://dx.doi.org/10.1128/JVI.03866-13,PMC3993769,,,"The coronavirus nucleocapsid (N) protein forms a helical ribonucleoprotein with the viral positive-strand RNA genome and binds to the principal constituent of the virion envelope, the membrane (M) protein, to facilitate assembly and budding. Besides these structural roles, N protein associates with a component of the replicase-transcriptase complex, nonstructural protein 3, at a critical early stage of infection. N protein has also been proposed to participate in the replication and selective packaging of genomic RNA and the transcription and translation of subgenomic mRNA. Coronavirus N proteins contain two structurally distinct RNA-binding domains, an unusual characteristic among RNA viruses. To probe the functions of these domains in the N protein of the model coronavirus mouse hepatitis virus (MHV), we constructed mutants in which each RNA-binding domain was replaced by its counterpart from the N protein of severe acute respiratory syndrome coronavirus (SARS-CoV). Mapping of revertants of the resulting chimeric viruses provided evidence for extensive intramolecular interactions between the two RNA-binding domains. Through analysis of viral RNA that was packaged into virions we identified the second of the two RNA-binding domains as a principal determinant of MHV packaging signal recognition. As expected, the interaction of N protein with M protein was not affected in either of the chimeric viruses. Moreover, the SARS-CoV N substitutions did not alter the fidelity of leader-body junction formation during subgenomic mRNA synthesis. These results more clearly delineate the functions of N protein and establish a basis for further exploration of the mechanism of genomic RNA packaging. IMPORTANCE This work describes the interactions of the two RNA-binding domains of the nucleocapsid protein of a model coronavirus, mouse hepatitis virus. The main finding is that the second of the two domains plays an essential role in recognizing the RNA structure that allows the selective packaging of genomic RNA into assembled virions.",,"['Kuo, Lili', 'Koetzner, Cheri A.', 'Hurst, Kelley R.', 'Masters, Paul S.']",,,,
,PMC,Large-Scale Nucleotide Optimization of Simian Immunodeficiency Virus Reduces Its Capacity To Stimulate Type I Interferon In Vitro,http://dx.doi.org/10.1128/JVI.03223-13,PMC3993766,,,"Lentiviral RNA genomes present a strong bias in their nucleotide composition with extremely high frequencies of A nucleotide in human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV). Based on the observation that human optimization of RNA virus gene fragments may abolish their ability to stimulate the type I interferon (IFN-I) response, we identified the most biased sequences along the SIV genome and showed that they are the most potent IFN-I stimulators. With the aim of designing an attenuated SIV genome based on a reduced capacity to activate the IFN-I response, we synthesized artificial SIV genomes whose biased sequences were optimized toward macaque average nucleotide composition without altering their regulatory elements or amino acid sequences. A synthetic SIV optimized with 169 synonymous mutations in gag and pol genes showed a 100-fold decrease in replicative capacity. Interestingly, a synthetic SIV optimized with 70 synonymous mutations in pol had a normal replicative capacity. Its ability to stimulate IFN-I was reduced when infected cells were cocultured with reporter cells. IFN regulatory factor 3 (IRF3) transcription factor was required for IFN-I stimulation, implicating cytosolic sensors in the detection of SIV-biased RNA in infected cells. No reversion of introduced mutations was observed for either of the optimized viruses after 10 serial passages. In conclusion, we have designed large-scale nucleotide-modified SIVs that may display attenuated pathogenic potential. IMPORTANCE In this study, we synthesized artificial SIV genomes in which the most hyperbiased sequences were optimized to bring them closer to the nucleotide composition of the macaque SIV host. Interestingly, we generated a stable synthetic SIV optimized with 70 synonymous mutations in pol gene, which had a normal replicative capacity but a reduced ability to stimulate type I IFN. This demonstrates the possibility to rationally change viral nucleotide composition to design replicative and genetically stable lentiviruses with attenuated pathogenic potentials.",,"['Vabret, Nicolas', 'Bailly-Bechet, Marc', 'Lepelley, Alice', 'Najburg, Valérie', 'Schwartz, Olivier', 'Verrier, Bernard', 'Tangy, Frédéric']",,,,
,PMC,Inhibition of Dengue and Chikungunya Virus Infections by RIG-I-Mediated Type I Interferon-Independent Stimulation of the Innate Antiviral Response,http://dx.doi.org/10.1128/JVI.03114-13,PMC3993760,,,"RIG-I is a cytosolic sensor critically involved in the activation of the innate immune response to RNA virus infection. In the present study, we evaluated the inhibitory effect of a RIG-I agonist on the replication of two emerging arthropod-borne viral pathogens, dengue virus (DENV) and chikungunya virus (CHIKV), for which no therapeutic options currently exist. We demonstrate that when a low, noncytotoxic dose of an optimized 5′triphosphorylated RNA (5′pppRNA) molecule was administered, RIG-I stimulation generated a robust antiviral response against these two viruses. Strikingly, 5′pppRNA treatment before or after challenge with DENV or CHIKV provided protection against infection. In primary human monocytes and monocyte-derived dendritic cells, the RIG-I agonist blocked both primary infection and antibody-dependent enhancement of DENV infection. The protective response against DENV and CHIKV induced by 5′pppRNA was dependent on an intact RIG-I/MAVS/TBK1/IRF3 axis and was largely independent of the type I IFN response. Altogether, this in vitro analysis of the antiviral efficacy of 5′pppRNA highlights the therapeutic potential of RIG-I agonists against emerging viruses such as DENV and CHIKV. IMPORTANCE DENV and CHIKV are two reemerging mosquito-borne viruses for which no therapeutic options currently exist. Both viruses overlap geographically in tropical regions of the world, produce similar fever-like symptoms, and are difficult to diagnose. This study investigated the inhibitory effect of a RIG-I agonist on the replication of these two viruses. RIG-I stimulation using 5′pppRNA before or after DENV or CHIKV infection generated a protective antiviral response against both pathogens in immune and nonimmune cells; interestingly, the protective response against the viruses was largely independent of the classical type I interferon response. The antiviral efficacy of 5′pppRNA highlights the therapeutic potential of RIG-I agonists against emerging viruses such as DENV and CHIKV.",,"['Olagnier, David', 'Scholte, Florine E. M.', 'Chiang, Cindy', 'Albulescu, Irina C.', 'Nichols, Carmen', 'He, Zhong', 'Lin, Rongtuan', 'Snijder, Eric J.', 'van Hemert, Martijn J.', 'Hiscott, John']",,,,
,PMC,"Identification of a Broad-Spectrum Antiviral Small Molecule against Severe Acute Respiratory Syndrome Coronavirus and Ebola, Hendra, and Nipah Viruses by Using a Novel High-Throughput Screening Assay",http://dx.doi.org/10.1128/JVI.03050-13,PMC3993759,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) and Ebola, Hendra, and Nipah viruses are members of different viral families and are known causative agents of fatal viral diseases. These viruses depend on cathepsin L for entry into their target cells. The viral glycoproteins need to be primed by protease cleavage, rendering them active for fusion with the host cell membrane. In this study, we developed a novel high-throughput screening assay based on peptides, derived from the glycoproteins of the aforementioned viruses, which contain the cathepsin L cleavage site. We screened a library of 5,000 small molecules and discovered a small molecule that can inhibit the cathepsin L cleavage of all viral peptides with minimal inhibition of cleavage of a host protein-derived peptide (pro-neuropeptide Y). The small molecule inhibited the entry of all pseudotyped viruses in vitro and the cleavage of SARS-CoV spike glycoprotein in an in vitro cleavage assay. In addition, the Hendra and Nipah virus fusion glycoproteins were not cleaved in the presence of the small molecule in a cell-based cleavage assay. Furthermore, we demonstrate that the small molecule is a mixed inhibitor of cathepsin L. Our broad-spectrum antiviral small molecule appears to be an ideal candidate for future optimization and development into a potent antiviral against SARS-CoV and Ebola, Hendra, and Nipah viruses. IMPORTANCE We developed a novel high-throughput screening assay to identify small molecules that can prevent cathepsin L cleavage of viral glycoproteins derived from SARS-CoV and Ebola, Hendra, and Nipah viruses that are required for their entry into the host cell. We identified a novel broad-spectrum small molecule that could block cathepsin L-mediated cleavage and thus inhibit the entry of pseudotypes bearing the glycoprotein derived from SARS-CoV or Ebola, Hendra, or Nipah virus. The small molecule can be further optimized and developed into a potent broad-spectrum antiviral drug.",,"['Elshabrawy, Hatem A.', 'Fan, Jilao', 'Haddad, Christine S.', 'Ratia, Kiira', 'Broder, Christopher C.', 'Caffrey, Michael', 'Prabhakar, Bellur S.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00507-14,PMC3993756,,,,,,,,,
,PMC,Identification of Herpesvirus Proteins That Contribute to G(1)/S Arrest,http://dx.doi.org/10.1128/JVI.00059-14,PMC3993752,,,"Lytic infection by herpesviruses induces cell cycle arrest at the G(1)/S transition. This appears to be a function of multiple herpesvirus proteins, but only a minority of herpesvirus proteins have been examined for cell cycle effects. To gain a more comprehensive understanding of the viral proteins that contribute to G(1)/S arrest, we screened a library of over 200 proteins from herpes simplex virus type 1, human cytomegalovirus, and Epstein-Barr virus (EBV) for effects on the G(1)/S interface, using HeLa fluorescent, ubiquitination-based cell cycle indicator (Fucci) cells in which G(1)/S can be detected colorimetrically. Proteins from each virus were identified that induce accumulation of G(1)/S cells, predominantly tegument, early, and capsid proteins. The identification of several capsid proteins in this screen suggests that incoming viral capsids may function to modulate cellular processes. The cell cycle effects of selected EBV proteins were further verified and examined for effects on p53 and p21 as regulators of the G(1)/S transition. Two EBV replication proteins (BORF2 and BMRF1) were found to induce p53 but not p21, while a previously uncharacterized tegument protein (BGLF2) was found to induce p21 protein levels in a p53-independent manner. Proteomic analyses of BGLF2-interacting proteins identified interactions with the NIMA-related protein kinase (NEK9) and GEM-interacting protein (GMIP). Silencing of either NEK9 or GMIP induced p21 without affecting p53 and abrogated the ability of BGLF2 to further induce p21. Collectively, these results suggest multiple viral proteins contribute to G(1)/S arrest, including BGLF2, which induces p21 levels likely by interfering with the functions of NEK9 and GMIP. IMPORTANCE Most people are infected with multiple herpesviruses, whose proteins alter the infected cells in several ways. During lytic infection, the viral proteins block cell proliferation just before the cellular DNA replicates. We used a novel screening method to identify proteins from three different herpesviruses that contribute to this block. Several of the proteins we identified had previously unknown functions or were structural components of the virion. Subsets of these proteins from Epstein-Barr virus were studied for their effects on the cell cycle regulatory proteins p53 and p21, thereby identifying two proteins that induce p53 and one that induces p21 (BGLF2). We identified interactions of BGLF2 with two human proteins, both of which regulate p21, suggesting that BGLF2 induces p21 by interfering with the functions of these two host proteins. Our study indicates that multiple herpesvirus proteins contribute to the cell proliferation block, including components of the incoming virions.",,"['Paladino, Patrick', 'Marcon, Edyta', 'Greenblatt, Jack', 'Frappier, Lori']",,,,
,PMC,Rotaviruses Reach Late Endosomes and Require the Cation-Dependent Mannose-6-Phosphate Receptor and the Activity of Cathepsin Proteases To Enter the Cell,http://dx.doi.org/10.1128/JVI.03457-13,PMC3993738,,,"Rotaviruses (RVs) enter cells through different endocytic pathways. Bovine rotavirus (BRV) UK uses clathrin-mediated endocytosis, while rhesus rotavirus (RRV) employs an endocytic process independent of clathrin and caveolin. Given the differences in the cell internalization pathway used by these viruses, we tested if the intracellular trafficking of BRV UK was the same as that of RRV, which is known to reach maturing endosomes (MEs) to infect the cell. We found that BRV UK also reaches MEs, since its infectivity depends on the function of Rab5, the endosomal sorting complex required for transport (ESCRT), and the formation of endosomal intraluminal vesicles (ILVs). However, unlike RRV, the infectivity of BRV UK was inhibited by knocking down the expression of Rab7, indicating that it has to traffic to late endosomes (LEs) to infect the cell. The requirement for Rab7 was also shared by other RV strains of human and porcine origin. Of interest, most RV strains that reach LEs were also found to depend on the activities of Rab9, the cation-dependent mannose-6-phosphate receptor (CD-M6PR), and cathepsins B, L, and S, suggesting that cellular factors from the trans-Golgi network (TGN) need to be transported by the CD-M6PR to LEs to facilitate RV cell infection. Furthermore, using a collection of UK × RRV reassortant viruses, we found that the dependence of BRV UK on Rab7, Rab9, and CD-M6PR is associated with the spike protein VP4. These findings illustrate the elaborate pathway of RV entry and reveal a new process (Rab9/CD-M6PR/cathepsins) that could be targeted for drug intervention. IMPORTANCE Rotavirus is an important etiological agent of severe gastroenteritis in children. In most instances, viruses enter cells through an endocytic pathway that delivers the viral particle to vesicular organelles known as early endosomes (EEs). Some viruses reach the cytoplasm from EEs, where they start to replicate their genome. However, other viruses go deeper into the cell, trafficking from EEs to late endosomes (LEs) to disassemble and reach the cytoplasm. In this work, we show that most RV strains have to traffic to LEs, and the transport of endolysosomal proteases from the Golgi complex to LEs, mediated by the mannose-6-phosphate receptor, is necessary for the virus to exit the vesicular compartment and efficiently start viral replication. We also show that this deep journey into the cell is associated with the virus spike protein VP4. These findings illustrate the elaborate pathway of RV entry that could be used for drug intervention.",,"['Díaz-Salinas, Marco A.', 'Silva-Ayala, Daniela', 'López, Susana', 'Arias, Carlos F.']",,,,
,PMC,Attenuation and Restoration of Severe Acute Respiratory Syndrome Coronavirus Mutant Lacking 2′-O-Methyltransferase Activity,http://dx.doi.org/10.1128/JVI.03571-13,PMC3993736,,,"The sudden emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and, more recently, Middle Eastern respiratory syndrome CoV (MERS-CoV) underscores the importance of understanding critical aspects of CoV infection and pathogenesis. Despite significant insights into CoV cross-species transmission, replication, and virus-host interactions, successful therapeutic options for CoVs do not yet exist. Recent identification of SARS-CoV NSP16 as a viral 2′-O-methyltransferase (2′-O-MTase) led to the possibility of utilizing this pathway to both attenuate SARS-CoV infection and develop novel therapeutic treatment options. Mutations were introduced into SARS-CoV NSP16 within the conserved KDKE motif and effectively attenuated the resulting SARS-CoV mutant viruses both in vitro and in vivo. While viruses lacking 2′-O-MTase activity had enhanced sensitivity to type I interferon (IFN), they were not completely restored in their absence in vivo. However, the absence of either MDA5 or IFIT1, IFN-responsive genes that recognize unmethylated 2′-O RNA, resulted in restored replication and virulence of the dNSP16 mutant virus. Finally, using the mutant as a live-attenuated vaccine showed significant promise for possible therapeutic development against SARS-CoV. Together, the data underscore the necessity of 2′-O-MTase activity for SARS-CoV pathogenesis and identify host immune pathways that mediate this attenuation. In addition, we describe novel treatment avenues that exploit this pathway and could potentially be used against a diverse range of viral pathogens that utilize 2′-O-MTase activity to subvert the immune system. IMPORTANCE Preventing recognition by the host immune response represents a critical aspect necessary for successful viral infection. Several viruses, including SARS-CoV, utilize virally encoded 2′-O-MTases to camouflage and obscure their viral RNA from host cell sensing machinery, thus preventing recognition and activation of cell intrinsic defense pathways. For SARS-CoV, the absence of this 2′-O-MTase activity results in significant attenuation characterized by decreased viral replication, reduced weight loss, and limited breathing dysfunction in mice. The results indicate that both MDA5, a recognition molecule, and the IFIT family play an important role in mediating this attenuation with restored virulence observed in their absence. Understanding this virus-host interaction provided an opportunity to design a successful live-attenuated vaccine for SARS-CoV and opens avenues for treatment and prevention of emerging CoVs and other RNA virus infections.",,"['Menachery, Vineet D.', 'Yount, Boyd L.', 'Josset, Laurence', 'Gralinski, Lisa E.', 'Scobey, Trevor', 'Agnihothram, Sudhakar', 'Katze, Michael G.', 'Baric, Ralph S.']",,,,
,PMC,Dynamic Imaging of the Hepatitis C Virus NS5A Protein during a Productive Infection,http://dx.doi.org/10.1128/JVI.02490-13,PMC3993538,,,"Hepatitis C virus (HCV) NS5A is essential for viral genome replication within cytoplasmic replication complexes and virus assembly at the lipid droplet (LD) surface, although its definitive functions are poorly understood. We developed approaches to investigate NS5A dynamics during a productive infection. We report here that NS5A motility and efficient HCV RNA replication require the microtubule network and the cytoplasmic motor dynein and demonstrate that both motile and relatively static NS5A-positive foci are enriched with host factors VAP-A and Rab5A. Pulse-chase imaging revealed that newly synthesized NS5A foci are small and distinct from aged foci, while further studies using a unique dual fluorescently tagged infectious HCV chimera showed a relatively stable association of NS5A foci with core-capped LDs. These results reveal new details about the dynamics and maturation of NS5A and the nature of potential sites of convergence of HCV replication and assembly pathways. IMPORTANCE Hepatitis C virus (HCV) is a major cause of serious liver disease worldwide. An improved understanding of the HCV replication cycle will enable development of novel and improved antiviral strategies. Here we have developed complementary fluorescent labeling and imaging approaches to investigate the localization, traffic and interactions of the HCV NS5A protein in living, virus-producing cells. These studies reveal new details as to the traffic, composition and biogenesis of NS5A foci and the nature of their association with putative sites of virus assembly.",,"['Eyre, Nicholas S.', 'Fiches, Guillaume N.', 'Aloia, Amanda L.', 'Helbig, Karla J.', 'McCartney, Erin M.', 'McErlean, Christopher S. P.', 'Li, Kui', 'Aggarwal, Anupriya', 'Turville, Stuart G.', 'Beard, Michael R.']",,,,
,PMC,Blocking of Exchange Proteins Directly Activated by cAMP Leads to Reduced Replication of Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.03001-13,PMC3993534,,,"The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infections and diseases represents a potential threat for worldwide spread and requires development of effective therapeutic strategies. In this study, we revealed a novel positive function of an exchange protein directly activated by cyclic AMP 1 (cAMP-1; Epac-1) on MERS-CoV replication. Specifically, we have shown that Epac-specific inhibitor treatment or silencing Epac-1 gene expression rendered cells resistant to viral infection. We believe Epac-1 inhibitors deserve further study as potential therapeutic agents for MERS-CoV infection.",,"['Tao, Xinrong', 'Mei, Feng', 'Agrawal, Anurodh', 'Peters, Clarence J.', 'Ksiazek, Thomas G.', 'Cheng, Xiaodong', 'Tseng, Chien-Te K.']",,,,
,PMC,Health Sector Initiatives for Disaster Risk Management in Ethiopia: A Narrative Review,http://dx.doi.org/10.1371/currents.dis.949664319ad451313b499f9c90cd9c0f,PMC3972256,24707445,CC BY,"Background: Natural and man-made disasters are prevailing in Ethiopia mainly due to drought, floods, landslides, earthquake, volcanic eruptions, and disease epidemics. Few studies so far have critically reviewed about medical responses to disasters and little information exists pertaining to the initiatives being undertaken by health sector from the perspective of basic disaster management cycle. This article aimed to review emergency health responses to disasters and other related interventions which have been undertaken in the health sector. Methods: Relevant documents were identified by searches in the websites of different sectors in Ethiopian and international non-governmental organizations and United Nations agencies. Using selected keywords, articles were also searched in the data bases of Medline, CINAHL, Scopus, and Google Scholar. In addition, pertinent articles from non-indexed journals were referred to. Results: Disaster management system in Ethiopia focused on response, recovery, and rehabilitation from 1974 to 1988; while the period between 1988 and 1993 marked the transition phase towards a more comprehensive approach. Theoretically, from 1993 onwards, the disaster management system has fully integrated the mitigation, prevention, and preparedness phases into already existing response and recovery approach, particularly for drought. This policy has changed the emergency response practices and the health sector has taken some initiatives in the area of emergency health care. Hence, drought early warning system, therapeutic feeding program in hospitals, health centers and posts in drought prone areas to manage promptly acute malnutrition cases have all been put in place. In addition, public health disease emergencies have been responded to at all levels of health care system. Conclusions: Emergency health responses to drought and its ramifications such as acute malnutrition and epidemics have become more comprehensive in the context of basic disaster management phases; and impacts of drought and epidemics seem to be declining. However, the remaining challenge is to address disasters arising from other hazards such as flooding in terms of mitigation, prevention, preparedness and integrating them in the health care system. Key Words: Disaster, Emergency Health, Health System, Ethiopia",2014 Apr 1,"['Tadesse, Luche', 'Ardalan, Ali']",PLoS Curr,,,
,PMC,A frameshifting stimulatory stem loop destabilizes the hybrid state and impedes ribosomal translocation,http://dx.doi.org/10.1073/pnas.1403457111,PMC3992627,,,"Ribosomal frameshifting occurs when a ribosome slips a few nucleotides on an mRNA and generates a new sequence of amino acids. Programmed −1 ribosomal frameshifting (−1PRF) is used in various systems to express two or more proteins from a single mRNA at precisely regulated levels. We used single-molecule fluorescence resonance energy transfer (smFRET) to study the dynamics of −1PRF in the Escherichia coli dnaX gene. The frameshifting mRNA (FSmRNA) contained the frameshifting signals: a Shine–Dalgarno sequence, a slippery sequence, and a downstream stem loop. The dynamics of ribosomal complexes translating through the slippery sequence were characterized using smFRET between the Cy3-labeled L1 stalk of the large ribosomal subunit and a Cy5-labeled tRNA(Lys) in the ribosomal peptidyl-tRNA–binding (P) site. We observed significantly slower elongation factor G (EF-G)–catalyzed translocation through the slippery sequence of FSmRNA in comparison with an mRNA lacking the stem loop, ΔSL. Furthermore, the P-site tRNA/L1 stalk of FSmRNA-programmed pretranslocation (PRE) ribosomal complexes exhibited multiple fluctuations between the classical/open and hybrid/closed states, respectively, in the presence of EF-G before translocation, in contrast with ΔSL-programmed PRE complexes, which sampled the hybrid/closed state approximately once before undergoing translocation. Quantitative analysis showed that the stimulatory stem loop destabilizes the hybrid state and elevates the energy barriers corresponding to subsequent substeps of translocation. The shift of the FSmRNA-programmed PRE complex equilibrium toward the classical/open state and toward states that favor EF-G dissociation apparently allows the PRE complex to explore alternative translocation pathways such as −1PRF.",,"['Kim, Hee-Kyung', 'Liu, Fei', 'Fei, Jingyi', 'Bustamante, Carlos', 'Gonzalez, Ruben L.', 'Tinoco, Ignacio']",,,,
,PMC,"Amodiaquine, an antimalarial drug, inhibits dengue virus type 2 replication and infectivity",http://dx.doi.org/10.1016/j.antiviral.2014.03.014,PMC4523242,,,"Dengue virus serotypes 1–4 (DENV1-4) are transmitted by mosquitoes which cause most frequent arboviral infections in the world resulting in ~390 million cases with ~25,000 deaths annually. There is no vaccine or antiviral drug currently available for human use. Compounds containing quinoline scaffold were shown to inhibit flavivirus NS2B-NS3 protease (NS2B-NS3pro) with good potencies. In this study, we screened quinoline derivatives, which are known antimalarial drugs for inhibition of DENV2 and West Nile virus (WNV) replication using the corresponding replicon expressing cell-based assays. Amodiaquine (AQ), one of the 4-aminoquinoline drugs, inhibited DENV2 infectivity measured by plaque assays, with EC(50) and EC(90) values of 1.08 ± 0.09 µM and 2.69 ± 0.47 µM, respectively, and DENV2 RNA replication measured by Renilla luciferase reporter assay, with EC(50) value of 7.41 ± 1.09 µM in the replicon expressing cells. Cytotoxic concentration (CC(50)) in BHK-21 cells was 52.09 ± 4.25 µM. The replication inhibition was confirmed by plaque assay of the extracellular virions as well as by qRT-PCR of the intracellular and extracellular viral RNA levels. AQ was stable for at least 96 h and had minor inhibitory effect on entry, translation, and post-replication stages in the viral life cycle. DENV protease, 5’-methyltransferase, and RNA-dependent RNA polymerase do not seem to be targets of AQ. Both p-hydroxyanilino and diethylaminomethyl moieties are important for AQ to inhibit DENV2 replication and infectivity. Our results support AQ as a promising candidate for anti-flaviviral therapy.",,"['Boonyasuppayakorn, Siwaporn', 'Reichert, Erin D.', 'Manzano, Mark', 'Nagarajan, Kuppuswamy', 'Padmanabhan, Radhakrishnan']",,,,
,PMC,Semiparametric Relative-risk Regression for Infectious Disease Transmission Data,http://dx.doi.org/10.1080/01621459.2014.896807,PMC4489164,,,"This paper introduces semiparametric relative-risk regression models for infectious disease data. The units of analysis in these models are pairs of individuals at risk of transmission. The hazard of infectious contact from i to j consists of a baseline hazard multiplied by a relative risk function that can be a function of infectiousness covariates for i, susceptibliity covariates for j, and pairwise covariates. When who-infects-whom is observed, we derive a profile likelihood maximized over all possible baseline hazard functions that is similar to the Cox partial likelihood. When who-infects-whom is not observed, we derive an EM algorithm to maximize the profile likelihood integrated over all possible combinations of who-infected-whom. This extends the most important class of regression models in survival analysis to infectious disease epidemiology. These methods can be implemented in standard statistical software, and they will be able to address important scientific questions about emerging infectious diseases with greater clarity, flexibility, and rigor than current statistical methods allow.",,"Kenah, Eben",,,,
,PMC,Antigen Sparing and Enhanced Protection Using A Novel rOv-ASP-1 Adjuvant in Aqueous Formulation with Influenza Vaccines,http://dx.doi.org/10.1016/j.vaccine.2014.03.046,PMC4080630,,,"Influenza is one of the most common infectious diseases endangering the health of humans, especially young children and the elderly. Although vaccination is the most effective means of protection against influenza, frequent mutations in viral surface antigens, low protective efficacy of the influenza vaccine in the elderly, slow production process and the potential of vaccine supply shortage during a pandemic are significant limitations of current vaccines. Adjuvants have been used to enhance the efficacy of a variety of vaccines; however, no adjuvant is included in current influenza vaccines approved in the United States. In this study, we found that a novel adjuvant, rOv-ASP-1, co-administrated with inactivated influenza vaccine using an aqueous formulation, substantially improved the influenza-specific antibody response and protection against lethal infection in a mouse model. rOv-ASP-1 enhanced the magnitude of the specific antibody response after immunization with low doses of influenza vaccine, allowing antigen-sparring by 10-fold. The rOv-ASP-1 formulated vaccine induced a more rapid response and a stronger Th1-associated antibody response compared to vaccine alone and to the vaccine formulated with the adjuvant alum. Importantly, rOv-ASP-1 significantly enhanced cross-reactive antibody responses and protection against challenge with an antigenically distinct strain. These results demonstrate that rOv-ASP-1 is an effective adjuvant that: 1) accelerates and enhances the specific antibody response induced by influenza vaccine; 2) allows for antigen sparing; and 3) augments a Th1-biased and cross-reactive antibody response that confers protection against an antigenically distinct strain.",,"['Jiang, Jiu', 'Fisher, Erin M.', 'Hensley, Scott E.', 'Lustigman, Sara', 'Murasko, Donna M.', 'Shen, Hao']",,,,
,PMC,Structure of a Conserved Golgi Complex-targeting Signal in Coronavirus Envelope Proteins,http://dx.doi.org/10.1074/jbc.M114.560094,PMC4007446,,,"Coronavirus envelope (CoV E) proteins are ∼100-residue polypeptides with at least one channel-forming α-helical transmembrane (TM) domain. The extramembrane C-terminal tail contains a completely conserved proline, at the center of a predicted β-coil-β motif. This hydrophobic motif has been reported to constitute a Golgi-targeting signal or a second TM domain. However, no structural data for this or other extramembrane domains in CoV E proteins is available. Herein, we show that the E protein in the severe acute respiratory syndrome virus has only one TM domain in micelles, whereas the predicted β-coil-β motif forms a short membrane-bound α-helix connected by a disordered loop to the TM domain. However, complementary results suggest that this motif is potentially poised for conformational change or in dynamic exchange with other conformations.",,"['Li, Yan', 'Surya, Wahyu', 'Claudine, Stephanie', 'Torres, Jaume']",,,,
,PMC,Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice,http://dx.doi.org/10.1073/pnas.1324022111,PMC3986188,,,"Mice genetically engineered to be humanized for their Ig genes allow for human antibody responses within a mouse background (HumAb mice), providing a valuable platform for the generation of fully human therapeutic antibodies. Unfortunately, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which their genetic humanization was carried out. Heretofore, HumAb mice have been generated by disrupting the endogenous mouse Ig genes and simultaneously introducing human Ig transgenes at a different and random location; KO-plus-transgenic humanization. As we describe in the companion paper, we attempted to make mice that more efficiently use human variable region segments in their humoral responses by precisely replacing 6 Mb of mouse Ig heavy and kappa light variable region germ-line gene segments with their human counterparts while leaving the mouse constant regions intact, using a unique in situ humanization approach. We reasoned the introduced human variable region gene segments would function indistinguishably in their new genetic location, whereas the retained mouse constant regions would allow for optimal interactions and selection of the resulting antibodies within the mouse environment. We show that these mice, termed VelocImmune mice because they were generated using VelociGene technology, efficiently produce human:mouse hybrid antibodies (that are rapidly convertible to fully human antibodies) and have fully functional humoral immune systems indistinguishable from those of WT mice. The efficiency of the VelocImmune approach is confirmed by the rapid progression of 10 different fully human antibodies into human clinical trials.",,"['Murphy, Andrew J.', 'Macdonald, Lynn E.', 'Stevens, Sean', 'Karow, Margaret', 'Dore, Anthony T.', 'Pobursky, Kevin', 'Huang, Tammy T.', 'Poueymirou, William T.', 'Esau, Lakeisha', 'Meola, Melissa', 'Mikulka, Warren', 'Krueger, Pamela', 'Fairhurst, Jeanette', 'Valenzuela, David M.', 'Papadopoulos, Nicholas', 'Yancopoulos, George D.']",,,,
,PMC,Genetic host specificity of hepatitis E virus,http://dx.doi.org/10.1016/j.meegid.2014.03.011,PMC5745802,,,"Hepatitis E virus (HEV) causes epidemic and sporadic cases of hepatitis worldwide. HEV genotypes 3 (HEV3) and 4 (HEV4) infect humans and animals, with swine being the primary reservoir. The relevance of HEV genetic diversity to host adaptation is poorly understood. We employed a Bayesian network (BN) analysis of HEV3 and HEV4 to detect epistatic connectivity among protein sites and its association with the host specificity in each genotype. The data imply coevolution among ~70% of polymorphic sites from all HEV proteins and association of numerous coevolving sites with adaptation to swine or humans. BN models for individual proteins and domains of the nonstructural polyprotein detected the host origin of HEV strains with accuracy of 74–93% and 63–87%, respectively. These findings, taken together with lack of phylogenetic association to host, suggest that the HEV host specificity is a heritable and convergent phenotypic trait achievable through variety of genetic pathways (abundance), and explain a broad host range for HEV3 and HEV4.",,"['Lara, James', 'Purdy, Michael A.', 'Khudyakov, Yury E.']",,,,
,PMC,Subviral Particle as Vaccine and Vaccine Platform,http://dx.doi.org/10.1016/j.coviro.2014.02.009,PMC4072748,,,"Recombinant subvirual particles retain similar antigenic features of their authentic viral capsids and thus have been applied as nonreplicating subunit vaccines against viral infection and illness. Additionally, the self-assembled, polyvalent subviral particles are excellent platforms to display foreign antigens for immune enhancement for vaccine development. These subviral particle-based vaccines are noninfectious and thus safer than the conventional live attenuated and inactivated vaccines. While several VLP vaccines are available in the markets, numerous others, including dual vaccines against more than one pathogen, are under clinical or preclinical development. This article provides an update of these efforts.",,"['Tan, Ming', 'Jiang, Xi']",,,,
,PMC,Measurement of CD8 and CD4 T Cell Responses in Mouse Lungs,,PMC4932852,,,Study of the adaptive immune response to a viral challenge in an animal model often includes analysis of the T cell response. Here we discuss in detail the methods that are used to characterize the CD8 and CD4 T cell response following viral challenge in the lung.,,"['Fett, Craig', 'Zhao, Jincun', 'Perlman, Stanley']",,,,
,PMC,Virus Infection and Titration of SARS-CoV in Mouse Lung,,PMC4932841,,,Two critical steps when investigating an animal model of a virus infection are consistently successfully infecting animals and accurately determining viral titers in tissue throughout the course of infection. Here we discuss in detail how to infect mice with SARS-CoV and then quantify the titer of virus in the lung.,,"['Fett, Craig', 'Zhao, Jincun', 'Perlman, Stanley']",,,,
,PMC,Constitutive Expression of Pentraxin 3 (PTX3) Protein by Human Amniotic Membrane Cells Leads to Formation of the Heavy Chain (HC)-Hyaluronan (HA)-PTX3 Complex,http://dx.doi.org/10.1074/jbc.M113.525287,PMC4036359,,,"Heavy chain (HC)-hyaluronan (HA), a complex formed by the covalent linkage between HC1 from the inter-α-trypsin inhibitor (IαI) and HA, purified from the human amniotic membrane (AM), is responsible for the anti-inflammatory, antiscarring, and antiangiogenic actions of the AM. This HC-HA complex is produced by constitutive expression of TNF-stimulated gene 6 and endogenous production of IαI by AM cells. Pentraxin 3 (PTX3), a prototypic long pentraxin that plays a non-redundant role in innate immunity against selected pathogens, also helps stabilize HC-HA to ensure female fertility. Here we noted strong positive PTX3 staining in the AM epithelium and compact stroma. PTX3 was constitutively expressed and secreted by cultured AM epithelial and stromal cells and, further, greatly up-regulated by TNF and IL-1β. Using an agarose overlay to trap the HA-containing matrix, the HC-HA-PTX3 complex was formed, as analyzed by Western blot analysis, by AM cells but not human skin fibroblasts, despite being cultured in the presence of serum and TNF. However, exogenous PTX3 helps human skin fibroblasts form the HC-HA-PTX3 complex with an agarose overlay. Furthermore, PTX3 can be coimmunoprecipitated with the HC-HA complex from agarose-overlaid AM cell extracts by an anti-human IαI antibody. Such a HC-HA-PTX3 complex can be reconstituted in vitro and exhibit similar effects as those reported for AM HC-HA-PTX3 on polarization of M2 macrophages. The tight binding between PTX3 and AM HC-HA withstands four runs of CsCl ultracentrifugation in the presence of 4 m GnHCl. These results indicate that PTX3 is constitutively expressed and secreted by AM cells as an integral component of the AM HC-HA-PTX3 complex and contributes to the biological function of AM HC-HA-PTX3.",,"['Zhang, Suzhen', 'Zhu, Ying-Ting', 'Chen, Szu-Yu', 'He, Hua', 'Tseng, Scheffer C. G.']",,,,
,PMC,Prevalence and Molecular Characterization of Human Metapneumovirus in Influenza A Negative Sample in Thailand,http://dx.doi.org/10.1002/jcla.21700,PMC6807631,,,"BACKGROUND: Human metapneumovirus (hMPV) causes respiratory tract infection in influenza‐like illness. The role of hMPV infections in all age groups in Thailand has not yet been investigated. Thus, the objective of this study was to determine prevalence of hMPV infection in all age groups in Thailand during 2011. METHODS: A total of 1,184 nasopharyngeal washes were collected from hospitalized patients and sent to the Department of Microbiology, Siriraj Hospital, for influenza A virus detection. Real‐time polymerase chain reaction (PCR) was used to detect hMPV infection. Partially, F gene from hMPV positive samples were sequenced and used for genotyping by phylogenetic tree analysis. RESULTS: The prevalence of hMPV for all age groups was 6.3%. The highest prevalence of hMPV infection was in children aged <2 years. Of 71 hMPV‐positive patients, three (4.2%) were coinfected with respiratory syncytial virus (RSV), two with rhinovirus (2.8%), one with coronavirus (1.4%), and one with RSV and adenovirus (1.4%). Phylogenetic analysis of F gene revealed that 96.8% of hMPV detected was subgenotype B1, 1.6% was sublineage A2a, and 1.6% was A2b. Genetic variation of F gene was much conserved. CONCLUSION: We demonstrated the prevalence of hMPV subgenotype B1 circulating in Thailand during 2011.",,"['Horthongkham, Navin', 'Athipanyasilp, Niracha', 'Sirijatuphat, Rujipas', 'Assanasen, Susan', 'Sutthent, Ruengpung']",,,,
,PMC,Influence of hydrophobic and electrostatic residues on SARS-coronavirus S2 protein stability: Insights into mechanisms of general viral fusion and inhibitor design,http://dx.doi.org/10.1002/pro.2442,PMC4005712,,,"Severe acute respiratory syndrome (SARS) is an acute respiratory disease caused by the SARS-coronavirus (SARS-CoV). SARS-CoV entry is facilitated by the spike protein (S), which consists of an N-terminal domain (S1) responsible for cellular attachment and a C-terminal domain (S2) that mediates viral and host cell membrane fusion. The SARS-CoV S2 is a potential drug target, as peptidomimetics against S2 act as potent fusion inhibitors. In this study, site-directed mutagenesis and thermal stability experiments on electrostatic, hydrophobic, and polar residues to dissect their roles in stabilizing the S2 postfusion conformation was performed. It was shown that unlike the pH-independent retroviral fusion proteins, SARS-CoV S2 is stable over a wide pH range, supporting its ability to fuse at both the plasma membrane and endosome. A comprehensive SARS-CoV S2 analysis showed that specific hydrophobic positions at the C-terminal end of the HR2, rather than electrostatics are critical for fusion protein stabilization. Disruption of the conserved C-terminal hydrophobic residues destabilized the fusion core and reduced the melting temperature by 30°C. The importance of the C-terminal hydrophobic residues led us to identify a 42-residue substructure on the central core that is structurally conserved in all existing CoV S2 fusion proteins (root mean squared deviation = 0.4 Å). This is the first study to identify such a conserved substructure and likely represents a common foundation to facilitate viral fusion. We have discussed the role of key residues in the design of fusion inhibitors and the potential of the substructure as a general target for the development of novel therapeutics against CoV infections.",,"['Aydin, Halil', 'Al-Khooly, Dina', 'Lee, Jeffrey E']",,,,
,PMC,Activation of circulated immune cells and inflammatory immune adherence are involved in the whole process of acute venous thrombosis,,PMC3992394,,,"Objective: To investigate localization and distribution of integrin subunit β1, β2 and β3 and morphological changes of ligand-recepter binding in thrombi of acute pulmonary embolism (PE) patients and explore activation of circulated immune cells, inflammatory immune adherence and coagulation response in acute venous thrombosis. Methods: Thrombi were collected from patients with acute PE. Immunohistochemistry was done to detect the expression and distribution of integrin β1, β2 and β3 in cells within thrombi, and ligands of integrin subunit β1, β2 and β3 were also determined by immunohistochemistry within the thrombi. Results: 1) Acute venous thrombi were red thrombi composed of skeletons and filamentous mesh containing large amounts of red blood cells and white blood cells; 2) Integrin subunit β1, β2 and β3 were expressed on lymphocytes, neutrophils and platelets; 3) No expression of integrin β1 ligands: Laminin, Fibronectin, Collagen I or Collagen-II on lymphocytes; integrin β2 ligands including ICAM, factor X and iC3b are distributed on neutrophils, and ligand fibrinogen bound to neutrophils; integrin β3 was expressed on platelets which form the skeleton of thrombi and bound to fibrinogen to construct mesh structure; 4) Factor Xa was expressed on the filamentous mesh; 5) Filamentous mesh was fully filled with red blood cell dominant blood cells. Conclusion: Acute venous thrombosis is an activation process of circulated lymphocytes, neutrophils and platelets mainly, and a whole process including integrin subunit β2 and β3 binding with their ligands. Activation of immune cells, inflammatory immune adherence and coagulation response are involved in the acute venous thrombosis.",,"['Wang, Le-Min', 'Duan, Qiang-Lin', 'Yang, Fan', 'Yi, Xiang-Hua', 'Zeng, Yu', 'Tian, Hong-Yan', 'Lv, Wei', 'Jin, Yun']",,,,
,PMC,A Histidine-rich Linker Region in Peptidylglycine α-Amidating Monooxygenase Has the Properties of a pH Sensor,http://dx.doi.org/10.1074/jbc.M113.545947,PMC4007436,,,"Decreasing luminal pH is thought to play a role in the entry of newly synthesized and endocytosed membrane proteins into secretory granules. The two catalytic domains of peptidylglycine α-amidating monooxygenase (PAM), a type I integral membrane protein, catalyze the sequential reactions that convert peptidyl-Gly substrates into amidated products. We explored the hypothesis that a conserved His-rich cluster (His-Gly-His-His) in the linker region connecting its two catalytic domains senses pH and affects PAM trafficking by mutating these His residues to Ala (Ala-Gly-Ala-Ala; H3A). Purified recombinant wild-type and H3A linker peptides were examined using circular dichroism and tryptophan fluorescence; mutation of the His cluster largely eliminated its pH sensitivity. An enzymatically active PAM protein with the same mutations (PAM-1/H3A) was expressed in HEK293 cells and AtT-20 corticotrope tumor cells. Metabolic labeling followed by immunoprecipitation revealed more rapid loss of newly synthesized PAM-1/H3A than PAM-1; although release of newly synthesized monofunctional PHM/H3A was increased, release of soluble bifunctional PAM/H3A, a product of the endocytic pathway, was decreased. Surface biotinylation revealed rapid loss of PAM-1/H3A, with no detectable return of the mutant protein to secretory granules. Consistent with its altered endocytic trafficking, little PAM-1/H3A was subjected to regulated intramembrane proteolysis followed by release of a small nuclear-targeted cytosolic fragment. AtT-20 cells expressing PAM-1/H3A adopted the morphology of wild-type AtT-20 cells; secretory products no longer accumulated in the trans-Golgi network and secretory granule exocytosis was more responsive to secretagogue.",,"['Vishwanatha, Kurutihalli', 'Bäck, Nils', 'Mains, Richard E.', 'Eipper, Betty A.']",,,,
,PMC,Phosphorylation of the Antiviral Protein Interferon-inducible Transmembrane Protein 3 (IFITM3) Dually Regulates Its Endocytosis and Ubiquitination,http://dx.doi.org/10.1074/jbc.M114.557694,PMC4002105,,,"Interferon-inducible transmembrane protein 3 (IFITM3) is essential for innate defense against influenza virus in mice and humans. IFITM3 localizes to endolysosomes where it prevents virus fusion, although mechanisms controlling its trafficking to this cellular compartment are not fully understood. We determined that both mouse and human IFITM3 are phosphorylated by the protein-tyrosine kinase FYN on tyrosine 20 (Tyr(20)) and that mouse IFITM3 is also phosphorylated on the non-conserved Tyr(27). Phosphorylation led to a cellular redistribution of IFITM3, including plasma membrane accumulation. Mutation of Tyr(20) caused a similar redistribution of IFITM3 and resulted in decreased antiviral activity against influenza virus, whereas Tyr(27) mutation of mouse IFITM3 showed minimal effects on localization or activity. Using FYN knockout cells, we also found that IFITM3 phosphorylation is not a requirement for its antiviral activity. Together, these results indicate that Tyr(20) is part of an endocytosis signal that can be blocked by phosphorylation or by mutation of this residue. Further mutagenesis narrowed this endocytosis-controlling region to four residues conforming to a YXXΦ (where X is any amino acid and Φ is Val, Leu, or Ile) endocytic motif that, when transferred to CD4, resulted in its internalization from the cell surface. Additionally, we found that phosphorylation of IFITM3 by FYN and mutagenesis of Tyr(20) both resulted in decreased IFITM3 ubiquitination. Overall, these results suggest that modification of Tyr(20) may serve in a cellular checkpoint controlling IFITM3 trafficking and degradation and demonstrate the complexity of posttranslational regulation of IFITM3.",,"['Chesarino, Nicholas M.', 'McMichael, Temet M.', 'Hach, Jocelyn C.', 'Yount, Jacob S.']",,,,
,PMC,Molecular control of monocyte development,http://dx.doi.org/10.1016/j.cellimm.2014.02.008,PMC4162862,,,"Monocyte development is a tightly regulated and multi-staged process, occurring through several defined progenitor cell intermediates. The key transcription factors, including PU.1, IRF8 and KLF4, growth factors, such as M-CSF and IL-34 and cytokines that drive monocyte development from hematopoietic progenitor cells are well defined. However, the molecular controls that direct differentiation into the Ly6C(hi) inflammatory and Ly6C(lo) monocyte subsets are yet to be completely elucidated. This review will provide a summary of the transcriptional regulation of monocyte development. We will also discuss how these molecular controls are also critical for microglial development despite their distinct haematopoetic origins. Furthermore, we will examine recent breakthroughs in defining mechanisms that promote differentiation of specific monocyte subpopulations.",,"['Terry, Rachael L.', 'Miller, Stephen D.']",,,,
,PMC,The Role of Influenza and Parainfluenza Infections in Nasopharyngeal Pneumococcal Acquisition Among Young Children,http://dx.doi.org/10.1093/cid/ciu148,PMC4001292,,,"Background. Animal models suggest that influenza infection favors nasopharyngeal acquisition of pneumococci. We assessed this relationship with influenza and other respiratory viruses in young children. Methods. A case-control study was nested within a prospective cohort study of acute respiratory illness (ARI) in Andean children <3 years of age (RESPIRA-PERU study). Weekly household visits were made to identify ARI and obtain nasal swabs for viral detection using real-time reverse-transcription polymerase chain reaction. Monthly nasopharyngeal (NP) samples were obtained to assess pneumococcal colonization. We determined whether specific respiratory viral ARI episodes occurring within the interval between NP samples increased the risk of NP acquisition of new pneumococcal serotypes. Results. A total of 729 children contributed 2128 episodes of observation, including 681 pneumococcal acquisition episodes (new serotype, not detected in prior sample), 1029 nonacquisition episodes (no colonization or persistent colonization with the same serotype as the prior sample), and 418 indeterminate episodes. The risk of pneumococcal acquisition increased following influenza-ARI (adjusted odds ratio [AOR], 2.19; 95% confidence interval [CI], 1.02–4.69) and parainfluenza-ARI (AOR, 1.86; 95% CI, 1.15–3.01), when compared with episodes without ARI. Other viral infections (respiratory syncytial virus, human metapneumovirus, human rhinovirus, and adenovirus) were not associated with acquisition. Conclusions. Influenza and parainfluenza ARIs appeared to facilitate pneumococcal acquisition among young children. As acquisition increases the risk of pneumococcal diseases, these observations are pivotal in our attempts to prevent pneumococcal disease.",,"['Grijalva, Carlos G.', 'Griffin, Marie R.', 'Edwards, Kathryn M.', 'Williams, John V.', 'Gil, Ana I.', 'Verastegui, Hector', 'Hartinger, Stella M.', 'Vidal, Jorge E.', 'Klugman, Keith P.', 'Lanata, Claudio F.']",,,,
,PMC,Single-dose live-attenuated Nipah virus vaccines confer complete protection by eliciting antibodies directed against surface glycoproteins,http://dx.doi.org/10.1016/j.vaccine.2014.02.087,PMC4829066,,,"BACKGROUND: Nipah virus (NiV), a zoonotic pathogen causing severe respiratory illness and encephalitis in humans, emerged in Malaysia in 1998 with subsequent outbreaks on an almost annual basis since 2001 in parts of the Indian subcontinent. The high case fatality rate, human-to-human transmission, wide-ranging reservoir distribution and lack of licensed intervention options are making NiV a serious regional and potential global public health problem. The objective of this study was to develop a fast-acting, single-dose NiV vaccine that could be implemented in a ring vaccination approach during outbreaks. METHODS: In this study we have designed new live-attenuated vaccine vectors based on recombinant vesicular stomatitis viruses (rVSV) expressing NiV glycoproteins (G or F) or nucleoprotein (N) and evaluated their protective efficacy in Syrian hamsters, an established NiV animal disease model. We further characterized the humoral immune response to vaccination in hamsters using ELISA and neutralization assays and performed serum transfer studies. RESULTS: Vaccination of Syrian hamsters with a single dose of the rVSV vaccine vectors resulted in strong humoral immune responses with neutralizing activities found only in those animals vaccinated with rVSV expressing NiV G or F proteins. Vaccinated animals with neutralizing antibody responses were completely protected from lethal NiV disease, whereas animals vaccinated with rVSV expressing NiV N showed only partial protection. Protection of NiV G or F vaccinated animals was conferred by antibodies, most likely the neutralizing fraction, as demonstrated by serum transfer studies. Protection of N-vaccinated hamsters was not antibody-dependent indicating a role of adaptive cellular responses for protection. CONCLUSIONS: The rVSV vectors expressing Nipah virus G or F are prime candidates for new ‘emergency vaccines’ to be utilized for NiV outbreak management.",,"['DeBuysscher, Blair L.', 'Scott, Dana', 'Marzi, Andrea', 'Prescott, Joseph', 'Feldmann, Heinz']",,,,
,PMC,Protective Immunity to H7N9 Influenza viruses elicited by synthetic DNA Vaccine,http://dx.doi.org/10.1016/j.vaccine.2014.02.038,PMC4221260,,,"Despite an intensive vaccine program influenza infections remain a major health problem, due to the viruses’ ability to change its envelope glycoprotein hemagglutinin (HA), through shift and drift, permitting influenza to escape protection induced by current vaccines or natural immunity. Recently a new variant, H7N9, has emerged in China causing global concern. First, there have been more than 130 laboratory-confirmed human infections resulting in an alarmingly high death rate (32.3%). Second, genetic changes found in H7N9 appear to be associated with enabling avian influenza viruses to spread more effectively in mammals, thus transmitting infections on a larger scale. Currently, no vaccines or drugs are effectively able to target H7N9. Here, we report the rapid development of a synthetic consensus DNA vaccine (pH7HA) to elicit potent protective immunity against the H7N9 viruses. We show that pH7HA induces broad antibody responses that bind to divergent HAs from multiple new members of the H7N9 family. These antibody responses result in high-titer HAI against H7N9. Simultaneously, this vaccine induces potent polyfunctional effector CD4 and CD8 T cell memory responses. Animals vaccinated with pH7HA are completely protected from H7N9 virus infection and any morbidity associated with lethal challenge. This study establishes that this synthetic consensus DNA vaccine represents a new tool for targeting emerging infection, and more importantly, its design, testing and development into seed stock for vaccine production in a few days in the pandemic setting has significant implications for the rapid deployment of vaccines protecting against emerging infectious diseases.",,"['Yan, Jian', 'Villarreal, Daniel O.', 'Racine, Trina', 'Chu, Jaemi S.', 'Walters, Jewell N.', 'Morrow, Matthew P.', 'Khan, Amir S.', 'Sardesai, Niranjan Y.', 'Kim, J. Joseph', 'Kobinger, Gary P.', 'Weiner, David B.']",,,,
,PMC,Uncovering Cryptic Glycan Markers in Multiple Sclerosis (MS) and Experimental Autoimmune Encephalomyelitis (EAE),http://dx.doi.org/10.1002/ddr.21169,PMC4019697,,,"[Table: see text] Using an integrated antigen microarray approach, we observed epitope-spreading of autoantibody responses to a variety of antigenic structures in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and in the serum of mice with experimental autoimmune encephalomyelitis (EAE). These included previously described protein- and lipid-based antigenic targets and newly discovered autoimmunogenic sugar moieties, notably, autoantibodies specific for the oligomannoses in both MS patient CSF and the sera of mice with EAE. These glycans are often masked by other sugar moieties and belong to a class of cryptic autoantigens. We further determined that these targets are highly expressed on multiple cell types in MS and EAE lesions. Co-immunization of SJL/J mice with a Man9-KLH conjugate at the time of EAE induction elicited highly significant levels of anti-Man9-cluster autoantibodies. Nevertheless, this anti-glycan autoantibody response was associated with a significantly reduced clinical severity of EAE. The potential of these cryptic glycan markers and targeting antibodies for diagnostic and therapeutic interventions of neurological disorders has yet to be explored.",,"['Wang, Denong', 'Bhat, Roopa', 'Sobel, Raymond A.', 'Huang, Wei', 'Wang, Lai-Xi', 'Olsson, Tomas', 'Steinman, Lawrence']",,,,
,PMC,Distinguishing Between Reservoir Exposure and Human-to-Human Transmission for Emerging Pathogens Using Case Onset Data,http://dx.doi.org/10.1371/currents.outbreaks.e1473d9bfc99d080ca242139a06c455f,PMC3946006,24619563,CC BY,"Pathogens such as MERS-CoV, influenza A/H5N1 and influenza A/H7N9 are currently generating sporadic clusters of spillover human cases from animal reservoirs. The lack of a clear human epidemic suggests that the basic reproductive number R0 is below or very close to one for all three infections. However, robust cluster-based estimates for low R0 values are still desirable so as to help prioritise scarce resources between different emerging infections and to detect significant changes between clusters and over time. We developed an inferential transmission model capable of distinguishing the signal of human-to-human transmission from the background noise of direct spillover transmission (e.g. from markets or farms). By simulation, we showed that our approach could obtain unbiased estimates of R0, even when the temporal trend in spillover exposure was not fully known, so long as the serial interval of the infection and the timing of a sudden drop in spillover exposure were known (e.g. day of market closure). Applying our method to data from the three largest outbreaks of influenza A/H7N9 outbreak in China in 2013, we found evidence that human-to-human transmission accounted for 13% (95% credible interval 1%–32%) of cases overall. We estimated R0 for the three clusters to be: 0.19 in Shanghai (0.01-0.49), 0.29 in Jiangsu (0.03-0.73); and 0.03 in Zhejiang (0.00-0.22). If a reliable temporal trend for the spillover hazard could be estimated, for example by implementing widespread routine sampling in sentinel markets, it should be possible to estimate sub-critical values of R0 even more accurately. Should a similar strain emerge with R0>1, these methods could give a real-time indication that sustained transmission is occurring with well-characterised uncertainty.",2014 Mar 7,"['Kucharski, Adam', 'Mills, Harriet', 'Pinsent, Amy', 'Fraser, Christophe', 'Van Kerkhove, Maria', 'Donnelly, Christl A.', 'Riley, Steven']",PLoS Curr,,,
,PMC,Nosocomial Transmission of Respiratory Syncytial Virus in an Outpatient Cancer Center,http://dx.doi.org/10.1016/j.bbmt.2014.02.024,PMC4036533,,,"BACKGROUND: Respiratory syncytial virus (RSV) outbreaks in inpatient settings are associated with poor outcomes in cancer patients. The use of molecular epidemiology to document RSV transmission in the outpatient setting has not been well described. METHODS: We performed a retrospective cohort study of two nosocomial outbreaks of RSV at the Seattle Cancer Care Alliance (SCCA). Subjects included patients seen at the SCCA with RSV detected in two outbreaks in 2007-2008 and 2012, and all employees with respiratory viruses detected in the 2007-2008 outbreak. A subset of samples was sequenced using semi-nested polymerase chain reaction targeting the RSV attachment glycoprotein coding region. RESULTS: Fifty-one cases of RSV were identified in 2007-2008. Clustering of identical viral strains was detected in 10 (67%) of 15 patients with RSV sequenced from 2007-2008. As part of a multimodal infection control strategy implemented as a response to the outbreak, symptomatic employees had nasal washes collected. Of 254 employee samples, 91 (34%) tested positive for a respiratory virus, including 14 with RSV. In another RSV outbreak in 2012, 24 cases of RSV were identified; nine (90%) of 10 patients had the same viral strain, and 1 (10%) had another viral strain. CONCLUSIONS: We document spread of clonal strains within an outpatient cancer care setting. Infection control interventions should be implemented in outpatient, as well as inpatient, settings to reduce person-to-person transmission and limit progression of RSV outbreaks.",,"['Chu, Helen Y.', 'Englund, Janet A.', 'Podczervinski, Sara', 'Kuypers, Jane', 'Campbell, Angela P.', 'Boeckh, Michael', 'Pergam, Steven A.', 'Casper, Crey']",,,,
,PMC,Social Media and Internet-Based Data in Global Systems for Public Health Surveillance: A Systematic Review,http://dx.doi.org/10.1111/1468-0009.12038,PMC3955375,,,"Context: The exchange of health information on the Internet has been heralded as an opportunity to improve public health surveillance. In a field that has traditionally relied on an established system of mandatory and voluntary reporting of known infectious diseases by doctors and laboratories to governmental agencies, innovations in social media and so-called user-generated information could lead to faster recognition of cases of infectious disease. More direct access to such data could enable surveillance epidemiologists to detect potential public health threats such as rare, new diseases or early-level warnings for epidemics. But how useful are data from social media and the Internet, and what is the potential to enhance surveillance? The challenges of using these emerging surveillance systems for infectious disease epidemiology, including the specific resources needed, technical requirements, and acceptability to public health practitioners and policymakers, have wide-reaching implications for public health surveillance in the 21st century. Methods: This article divides public health surveillance into indicator-based surveillance and event-based surveillance and provides an overview of each. We did an exhaustive review of published articles indexed in the databases PubMed, Scopus, and Scirus between 1990 and 2011 covering contemporary event-based systems for infectious disease surveillance. Findings: Our literature review uncovered no event-based surveillance systems currently used in national surveillance programs. While much has been done to develop event-based surveillance, the existing systems have limitations. Accordingly, there is a need for further development of automated technologies that monitor health-related information on the Internet, especially to handle large amounts of data and to prevent information overload. The dissemination to health authorities of new information about health events is not always efficient and could be improved. No comprehensive evaluations show whether event-based surveillance systems have been integrated into actual epidemiological work during real-time health events. Conclusions: The acceptability of data from the Internet and social media as a regular part of public health surveillance programs varies and is related to a circular challenge: the willingness to integrate is rooted in a lack of effectiveness studies, yet such effectiveness can be proved only through a structured evaluation of integrated systems. Issues related to changing technical and social paradigms in both individual perceptions of and interactions with personal health data, as well as social media and other data from the Internet, must be further addressed before such information can be integrated into official surveillance systems.",,"['VELASCO, EDWARD', 'AGHENEZA, TUMACHA', 'DENECKE, KERSTIN', 'KIRCHNER, GÖRAN', 'ECKMANNS, TIM']",,,,
,PMC,Parainfluenza Virus Lower Respiratory Tract Disease After Hematopoietic Cell Transplant: Viral Detection in the Lung Predicts Outcome,http://dx.doi.org/10.1093/cid/ciu134,PMC4001290,,,"Background. Parainfluenza virus (PIV) commonly infects patients following hematopoietic cell transplantation (HCT), frequently causing lower respiratory tract disease (LRTD). The definition of LRTD significantly differs among studies evaluating the impact of PIV after HCT. Methods. We retrospectively evaluated 544 HCT recipients with laboratory-confirmed PIV and classified LRTD into 3 groups: possible (PIV detection in upper respiratory tract with new pulmonary infiltrates with/without LRTD symptoms), probable (PIV detection in lung with LRTD symptoms without new pulmonary infiltrates), and proven (PIV detection in lung with new pulmonary infiltrates with/without LRTD symptoms). Results. Probabilities of 90-day survival after LRTD were 87%, 58%, and 45% in possible, probable, and proven cases, respectively. Patients with probable and proven LRTD had significantly worse survival than those with upper respiratory tract infection (probable: hazard ratio [HR], 5.87 [P < .001]; proven: HR, 9.23 [P < .001]), whereas possible LRTD did not (HR, 1.49 [P = .27]). Among proven/probable cases, oxygen requirement at diagnosis, low monocyte counts, and high-dose steroid use (>2 mg/kg/day) were associated with high mortality in multivariable analysis. Conclusions. PIV LRTD with viral detection in lungs (proven/probable LRTD) was associated with worse outcomes than was PIV LRTD with viral detection in upper respiratory samples alone (possible LRTD). This new classification should impact clinical trial design and permit comparability of results among centers.",,"['Seo, Sachiko', 'Xie, Hu', 'Campbell, Angela P.', 'Kuypers, Jane M.', 'Leisenring, Wendy M.', 'Englund, Janet A.', 'Boeckh, Michael']",,,,
,PMC,Two Alternative Ways of Start Site Selection in Human Norovirus Reinitiation of Translation,http://dx.doi.org/10.1074/jbc.M114.554030,PMC4002083,,,"The calicivirus minor capsid protein VP2 is expressed via termination/reinitiation. This process depends on an upstream sequence element denoted termination upstream ribosomal binding site (TURBS). We have shown for feline calicivirus and rabbit hemorrhagic disease virus that the TURBS contains three sequence motifs essential for reinitiation. Motif 1 is conserved among caliciviruses and is complementary to a sequence in the 18 S rRNA leading to the model that hybridization between motif 1 and 18 S rRNA tethers the post-termination ribosome to the mRNA. Motif 2 and motif 2* are proposed to establish a secondary structure positioning the ribosome relative to the start site of the terminal ORF. Here, we analyzed human norovirus (huNV) sequences for the presence and importance of these motifs. The three motifs were identified by sequence analyses in the region upstream of the VP2 start site, and we showed that these motifs are essential for reinitiation of huNV VP2 translation. More detailed analyses revealed that the site of reinitiation is not fixed to a single codon and does not need to be an AUG, even though this codon is clearly preferred. Interestingly, we were able to show that reinitiation can occur at AUG codons downstream of the canonical start/stop site in huNV and feline calicivirus but not in rabbit hemorrhagic disease virus. Although reinitiation at the original start site is independent of the Kozak context, downstream initiation exhibits requirements for start site sequence context known for linear scanning. These analyses on start codon recognition give a more detailed insight into this fascinating mechanism of gene expression.",,"['Luttermann, Christine', 'Meyers, Gregor']",,,,
,PMC,Rapid generation of a mouse model for Middle East respiratory syndrome,http://dx.doi.org/10.1073/pnas.1323279111,PMC3977243,,,"In this era of continued emergence of zoonotic virus infections, the rapid development of rodent models represents a critical barrier to public health preparedness, including the testing of antivirus therapy and vaccines. The Middle East respiratory syndrome coronavirus (MERS-CoV) was recently identified as the causative agent of a severe pneumonia. Given the ability of coronavirus to rapidly adapt to new hosts, a major public health concern is that MERS-CoV will further adapt to replication in humans, triggering a pandemic. No small-animal model for this infection is currently available, but studies suggest that virus entry factors can confer virus susceptibility. Here, we show that mice were sensitized to MERS-CoV infection by prior transduction with adenoviral vectors expressing the human host-cell receptor dipeptidyl peptidase 4. Mice developed a pneumonia characterized by extensive inflammatory-cell infiltration with virus clearance occurring 6–8 d after infection. Clinical disease and histopathological changes were more severe in the absence of type-I IFN signaling whereas the T-cell response was required for virus clearance. Using these mice, we demonstrated the efficacy of a therapeutic intervention (poly I:C) and a potential vaccine [Venezuelan equine encephalitis replicon particles expressing MERS-CoV spike protein]. We also found little protective cross-reactivity between MERS-CoV and the severe acute respiratory syndrome-CoV. Our results demonstrate that this system will be useful for MERS-CoV studies and for the rapid development of relevant animal models for emerging respiratory viral infections.",,"['Zhao, Jincun', 'Li, Kun', 'Wohlford-Lenane, Christine', 'Agnihothram, Sudhakar S.', 'Fett, Craig', 'Zhao, Jingxian', 'Gale, Michael J.', 'Baric, Ralph S.', 'Enjuanes, Luis', 'Gallagher, Tom', 'McCray, Paul B.', 'Perlman, Stanley']",,,,
,PMC,Sore throat,,PMC3948435,,,"INTRODUCTION: About 10% of people present to primary healthcare services with sore throat each year. The causative organisms of sore throat may be bacteria (most commonly Streptococcus) or viruses (typically rhinovirus), although it is difficult to distinguish bacterial from viral infections clinically. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to reduce symptoms of acute infective sore throat? We searched Medline, Embase, The Cochrane Library, and other important databases up to September 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 6 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antibiotics, corticosteroids, non-steroidal anti-inflammatory drugs, and paracetamol.",,"Kenealy, Tim",,,,
,PMC,Generation of improved humanized mouse models for human infectious diseases,http://dx.doi.org/10.1016/j.jim.2014.02.011,PMC4155027,,,"The study of human-specific infectious agents has been hindered by the lack of optimal small animal models. More recently development of novel strains of immunodeficient mice has begun to provide the opportunity to utilize small animal models for the study of many human-specific infectious agents. The introduction of a targeted mutation in the IL2 receptor common gamma chain gene (IL2rg(null)) in mice already deficient in T and B cells led to a breakthrough in the ability to engraft hematopoietic stem cells, as well as functional human lymphoid cells and tissues, effectively creating human immune systems in immunodeficient mice. These humanized mice are becoming increasingly important as pre-clinical models for the study of human immunodeficiency virus-1 (HIV-1) and other human-specific infectious agents. However, there remain a number of opportunities to further improve humanized mouse models for the study of human-specific infectious agents. This is being done by the implementation of innovative technologies, which collectively will accelerate the development of new models of genetically modified mice, including; i) modifications of the host to reduce innate immunity, which impedes human cell engraftment; ii) genetic modification to provide human-specific growth factors and cytokines required for optimal human cell growth and function; iii) and new cell and tissue engraftment protocols. The development of “next generation” humanized mouse models continues to provide exciting opportunities for the establishment of robust small animal models to study the pathogenesis of human-specific infectious agents, as well as for testing the efficacy of therapeutic agents and experimental vaccines.",,"['Brehm, Michael A.', 'Wiles, Michael V.', 'Greiner, Dale L.', 'Shultz, Leonard D.']",,,,
,PMC,Exposure to Influenza Virus Aerosols in the Hospital Setting: Is Routine Patient Care an Aerosol Generating Procedure?,http://dx.doi.org/10.1093/infdis/jiu127,PMC4624392,,,,,"['Cummings, Kristin J.', 'Martin, Stephen B.', 'Lindsley, William G.', 'Othumpangat, Sreekumar', 'Blachere, Francoise M.', 'Noti, John D.', 'Beezhold, Donald H.', 'Roidad, Nasira', 'Parker, John E.', 'Weissman, David N.']",,,,
,PMC,PKR mediated regulation of inflammation and IL-10 during viral encephalomyelitis,http://dx.doi.org/10.1016/j.jneuroim.2014.02.012,PMC4019976,,,"Double-stranded RNA-dependent protein kinase (PKR) regulates antiviral activity, immune responses, apoptosis and neurotoxicity. Gliatropic coronavirus infection induced PKR activation in infected as well uninfected cells within the central nervous system (CNS). However, PKR deficiency only modestly increased viral replication and did not affect IFN-α/β or IL-1β expression. Despite reduced Il-6, Ccl5, and Cxcl10 mRNA, protein levels remained unaltered. Furthermore, PKR deficiency selectively reduced IL-10 production in CD4, but not CD8 T cells, without affecting CNS pathology. The results demonstrate the ability of PKR to balance neuroinflammation by selectively modulating key cytokines and chemokines in CNS resident and CD4 T cells.",,"['Kapil, Parul', 'Stohlman, Stephen A.', 'Hinton, David R.', 'Bergmann, Cornelia C.']",,,,
,PMC,Development and evaluation of SYBR Green-I based quantitative PCR assays for herpes simplex virus type 1 whole transcriptome analysis,http://dx.doi.org/10.1016/j.jviromet.2014.02.010,PMC4041175,,,"There is an emerging need for viral gene specific quantitative PCR (qPCR) assays that validate and complement whole transcriptome level technologies, including microarray and next generation sequencing. Therefore, a compilation of qPCR assays that represented the breadth of the entire Herpes simplex virus type 1 (HSV-1) genome were developed and evaluated. SYBR Green-I-based quantitation of each of the 74 HSV-1 lytic genes enabled accurate and reproducible detection of viral genes using a minimal number of reaction conditions. The amplification specificity of these assays for HSV-1 target genes was confirmed by amplicon size and purity determination on agarose gels, melt temperature dissociation curve analysis, and direct DNA sequencing of amplified products. Analysis of representative target genes demonstrated that these assays accurately and reproducibly quantified target gene expression across a wide and linear range of detection. In addition, minimal intra- and inter-assay variability was observed with significant well-to-well and plate-to-plate/assay-to-assay precision. To evaluate the utility of the developed qPCR assay system, kinetic profiles of viral gene expression were determined for an array of representative genes from all HSV-1 transcriptional gene classes. Collectively, these data demonstrate that the compiled optimized qPCR assays is a scalable and cost-effective method to assess HSV-1 gene expression with broad application potential, including investigation of pathogenesis and antiviral therapies. In addition, they can be employed to validate and complement evolving technologies for genome-wide transcriptome analysis.",,"['Garvey, Cathryn E.', 'McGowin, Chris L.', 'Foster, Timothy P.']",,,,
,PMC,Strength of a bifurcated H bond,http://dx.doi.org/10.1073/pnas.1319827111,PMC3964065,,,"Macromolecules are characterized by their particular arrangement of H bonds. Many of these interactions involve a single donor and acceptor pair, such as the regular H-bonding pattern between carbonyl oxygens and amide H(+)s four residues apart in α-helices. The H-bonding potential of some acceptors, however, leads to the phenomenon of overcoordination between two donors and one acceptor. Herein, using isotope-edited Fourier transform infrared measurements and density functional theory (DFT) calculations, we measured the strength of such bifurcated H bonds in a transmembrane α-helix. Frequency shifts of the (13)C=(18)O amide I mode were used as a reporter of the strength of the bifurcated H bond from a thiol and hydroxyl H(+) at residue i + 4. DFT calculations yielded very similar frequency shifts and an energy of −2.6 and −3.4 kcal/mol for the thiol and hydroxyl bifurcated H bonds, respectively. The strength of the intrahelical bifurcated H bond is consistent with its prevalence in hydrophobic environments and is shown to significantly impact side-chain rotamer distribution.",,"['Feldblum, Esther S.', 'Arkin, Isaiah T.']",,,,
,PMC,Angiotensin Converting Enzyme 2/Ang‐(1–7)/Mas Axis Protects Brain from Ischemic Injury with a Tendency of Age‐dependence,http://dx.doi.org/10.1111/cns.12233,PMC4840841,,,"BACKGROUND: The angiotensin (Ang) converting enzyme 2 (ACE2)/Ang‐(1‐7)/Mas receptor pathway is an important component of the renin–angiotensin system and has been suggested to exert beneficial effects in ischemic stroke. AIMS: This study explored whether the ACE2/Ang‐(1‐7)/Mas pathway has a protective effect on cerebral ischemic injury and whether this effect is affected by age. METHODS: We used three‐month and eight‐month transgenic mice with neural over‐expression of ACE2 (SA) and their age‐matched nontransgenic (NT) controls. Neurological deficits and ischemic stroke volume were determined following middle cerebral artery occlusion (MCAO). In oxygen and glucose deprivation (OGD) experiments on brain slices, the effects of the Mas receptor agonist (Ang1‐7) or antagonist (A779) on tissue swelling, Nox2/Nox4 expression reactive oxygen species (ROS) production and cell death were measured. RESULTS: (1) Middle cerebral artery occlusion ‐induced ischemic injury and neurological deficit were reduced in SA mice, especially in eight‐month animals; (2) OGD‐induced tissue swelling and cell death were decreased in SA mice with a greater reduction seen in eight‐month mice; (3) Ang‐(1–7) and A779 had opposite effects on OGD‐induced responses, which correlated with changes in Nox2/Nox4 expression and ROS production. CONCLUSIONS: Angiotensin converting enzyme 2/Ang‐(1‐7)/Mas axis protects brain from ischemic injury via the Nox/ROS signaling pathway, with a greater effect in older animals.",,"['Zheng, Jiao‐Lin', 'Li, Guang‐Ze', 'Chen, Shu‐Zhen', 'Wang, Jin‐Ju', 'Olson, James E.', 'Xia, Hui‐Jing', 'Lazartigues, Eric', 'Zhu, Yu‐Lan', 'Chen, Yan‐Fang']",,,,
,PMC,Comparison of Viral Load in Individuals with and without Asthma during Infections with Rhinovirus,http://dx.doi.org/10.1164/rccm.201310-1767OC,PMC3977713,,,"Rationale: Most virus-induced attacks of asthma are caused by rhinoviruses (RVs). Objectives: To determine whether people with asthma are susceptible to an increased viral load during RV infection. Methods: Seventy-four children (4–18 yr old) were enrolled; 28 with wheezing, 32 with acute rhinitis, and 14 without respiratory tract symptoms. Nasal washes were evaluated using quantitative polymerase chain reaction for RV to judge viral load along with gene sequencing to identify strains of RV. Soluble intercellular adhesion molecule-1, IFN-λ(1), and eosinophil cationic protein in nasal washes, along with blood eosinophil counts and total and allergen-specific IgE in sera, were also evaluated. Similar assessments were done in 24 young adults (16 with asthma, 8 without) who participated in an experimental challenge with RV (serotype 16). Measurements and Main Results: Fifty-seven percent of wheezing children and 56% with acute rhinitis had nasal washes testing positive for RV. The geometric mean of viral loads by quantitative polymerase chain reaction in washes from wheezing children was 2.8-fold lower, but did not differ significantly from children with rhinitis (7,718 and 21,612 copies of viral RNA per microliter nasal wash, respectively; P = 0.48). The odds for wheezing were increased if children who tested positive for RV were sensitized to one or more allergens (odds ratio, 3.9; P = 0.02). Similarly, neither peak nor cumulative viral loads differed significantly in washes from adults with asthma compared with those without asthma during the experimental RV challenge. Conclusions: During acute symptoms, children infected with RV enrolled for wheezing or acute rhinitis had similar viral loads in their nasal washes, as did adults with and without asthma infected with RV-16 experimentally.",,"['Kennedy, Joshua L.', 'Shaker, Marcus', 'McMeen, Victoria', 'Gern, James', 'Carper, Holliday', 'Murphy, Deborah', 'Lee, Wai-Ming', 'Bochkov, Yury A.', 'Vrtis, Rose F.', 'Platts-Mills, Thomas', 'Patrie, James', 'Borish, Larry', 'Steinke, John W.', 'Woods, William A.', 'Heymann, Peter W.']",,,,
,PMC,“Watch Out! Pneumonia Secondary to Achromobacter Denitrificans”,http://dx.doi.org/10.4103/2141-9248.131700,PMC4083727,25031900,CC BY-NC-SA,"Pneumonia is the cause of significant morbidity and mortality especially in developing countries. The frequency and importance of emerging new pathogens have significant implications for therapy. We report a case of pneumonia caused by a very rare organism, Achromobacter denitrificans which was treated successfully with intravenous meropenem injections for 14 days. Review of available literature has documentation of isolation of Achromobacter xylosoxidans from endotracheal aspirate culture but this is probably the first case of pneumonia due to A. denitrificans.",2014 Mar-Apr,"['Aundhakar, SC', 'Mane, MB', 'Bharadiya, AA', 'Pawar, SK']",Ann Med Health Sci Res,,,
,PMC,Evidence-based medicine vital for health and medical progress in China,http://dx.doi.org/10.2471/BLT.14.030314,PMC3949601,,,Evidence-based medicine – using the best available evidence to make decisions about individual patients’ care — holds vast untapped potential for improving health in China. Youping Li talks to Ursula Zhao.,,,,,,
,PMC,"AMMI Canada – CACMID Annual Conference: April 2–5, 2014, Victoria, British Columbia",,PMC4028677,,,,,,,,,
,PMC,ACE2: Angiotensin II/Angiotensin-(1-7) balance in cardiorenal injury,http://dx.doi.org/10.1007/s11906-014-0420-5,PMC4286874,,,"Our current recognition of the renin-angiotensin system is more convoluted than originally thought due to the discovery of multiple novel enzymes, peptides, and receptors inherent to this interactive biochemical cascade. Over the last decade angiotensin converting enzyme 2 (ACE2) has emerged as a key player in the pathophysiology of hypertension and cardiovascular and renal disease due to its pivotal role in metabolizing vasoconstrictive/hypertrophic/proliferative angiotensin II into favorable angiotensin-(1-7). This review addresses a considerable advancement in research on the role of tissue ACE2 in development and progression of hypertension and cardiorenal injury. We also summarize the results from recent clinical and experimental studies suggesting that serum or urine soluble ACE2 may serve as a novel biomarker or independent risk factor relevant for diagnosis and prognosis of cardiorenal disease. Recent proceedings on novel therapeutic approaches to enhance ACE2/angiotensin-(1-7) axis are also reviewed.",,"['Varagic, Jasmina', 'Ahmad, Sarfaraz', 'Nagata, Sayaka', 'Ferrario, Carlos M.']",,,,
,PMC,Untangling Membrane Rearrangement in the Nidovirales,http://dx.doi.org/10.1089/dna.2013.2304,PMC3942677,,,"All known positive sense single-stranded RNA viruses induce host cell membrane rearrangement for purposes of aiding viral genome replication and transcription. Members of the Nidovirales order are no exception, inducing intricate regions of double membrane vesicles and convoluted membranes crucial for the production of viral progeny. Although these structures have been well studied for some members of this order, much remains unclear regarding the biogenesis of these rearranged membranes. Here, we discuss what is known about these structures and their formation, compare some of the driving viral proteins behind this process across the nidovirus order, and examine possible routes of mechanism by which membrane rearrangement may occur.",,"['Angelini, Megan Mary', 'Neuman, Benjamin William', 'Buchmeier, Michael J.']",,,,
,PMC,COULD INTERFERON-GAMMA BE A THERAPEUTIC TARGET FOR TREATING HEART FAILURE?,http://dx.doi.org/10.1007/s10741-013-9393-8,PMC3844057,,,"The cytokine interferon-gamma (IFN-γ), is the only known member of the type II family of interferons, and as such, binds to its own distinct receptor. It is important in host defense against infection, as well as adaptive immune responses. Whilst a wide array of cytokines are known to be involved in adverse remodeling of the heart and the progression to heart failure, the role of IFN-γ is unclear. Recent evidence from clinical studies, animal models of myocarditis and hypertension, as well as isolated cell studies, provide conflicting data as to whether IFN-γ is pathological or protective in the heart. Thus, it is important to highlight these discrepant findings so that areas of future investigation can be identified to more clearly determine the precise role of IFN-γ in the heart. Accordingly, this review will: 1) discuss the source of IFN-γ in the diseased heart; 2) summarize the data from animal studies; 3) discuss the effects of IFN-γ on isolated cardiac fibroblasts and cardiomyocytes; 4) identify signaling mechanisms that may be invoked by IFN-γ in the heart; and 5) present the clinical evidence supporting a role for IFN-γ in heart failure.",,"['Levick, Scott P.', 'Goldspink, Paul H.']",,,,
,PMC,Antiviral T-cell therapy,http://dx.doi.org/10.1111/imr.12138,PMC3927231,,,"Serious viral infections are a common cause of morbidity and mortality after allogeneic stem cell transplantation. They occur in the majority of allograft recipients and are fatal in 17–20%. These severe infections may be prolonged or recurrent and add substantially to the cost, both human and financial, of the procedure. Many features of allogeneic stem cell transplantation contribute to this high rate of viral disease. The cytotoxic and immunosuppressive drugs administered pre-transplant to eliminate the host hematopoietic/immune system and any associated malignancy, the delay in recapitulating immune ontogeny post-transplant, the immunosuppressive drugs given to prevent graft versus host disease (GvHD), and the effects of GvHD itself, all serve to make stem cell transplant recipients vulnerable to disease from endogenous (latent) and exogenous (community) viruses, and to be incapable of controlling them as quickly and effectively as most normal individuals.",,"['Leen, Ann M', 'Heslop, Helen E', 'Brenner, Malcolm K']",,,,
,PMC,Guidelines for prevention of hospital acquired infections,http://dx.doi.org/10.4103/0972-5229.128705,PMC3963198,24701065,CC BY-NC-SA,"These guidelines, written for clinicians, contains evidence-based recommendations for the prevention of hospital acquired infections Hospital acquired infections are a major cause of mortality and morbidity and provide challenge to clinicians. Measures of infection control include identifying patients at risk of nosocomial infections, observing hand hygiene, following standard precautions to reduce transmission and strategies to reduce VAP, CR-BSI, CAUTI. Environmental factors and architectural lay out also need to be emphasized upon. Infection prevention in special subsets of patients - burns patients, include identifying sources of organism, identification of organisms, isolation if required, antibiotic prophylaxis to be used selectively, early removal of necrotic tissue, prevention of tetanus, early nutrition and surveillance. Immunodeficient and Transplant recipients are at a higher risk of opportunistic infections. The post tranplant timetable is divided into three time periods for determining risk of infections. Room ventilation, cleaning and decontamination, protective clothing with care regarding food requires special consideration. Monitoring and Surveillance are prioritized depending upon the needs. Designated infection control teams should supervise the process and help in collection and compilation of data. Antibiotic Stewardship Recommendations include constituting a team, close coordination between teams, audit, formulary restriction, de-escalation, optimizing dosing, active use of information technology among other measure. The recommendations in these guidelines are intended to support, and not replace, good clinical judgment. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments.",2014 Mar,"['Mehta, Yatin', 'Gupta, Abhinav', 'Todi, Subhash', 'Myatra, SN', 'Samaddar, D. P.', 'Patil, Vijaya', 'Bhattacharya, Pradip Kumar', 'Ramasubban, Suresh']",Indian J Crit Care Med,,,
,PMC,The Bordetella bronchiseptica Type III Secretion System Is Required for Persistence and Disease Severity but Not Transmission in Swine,http://dx.doi.org/10.1128/IAI.01115-13,PMC3957984,,,"Bordetella bronchiseptica is pervasive in swine populations and plays multiple roles in respiratory disease. Most studies addressing virulence factors of B. bronchiseptica utilize isolates derived from hosts other than pigs in conjunction with rodent infection models. Based on previous in vivo mouse studies, we hypothesized that the B. bronchiseptica type III secretion system (T3SS) would be required for maximal disease severity and persistence in the swine lower respiratory tract. To examine the contribution of the T3SS to the pathogenesis of B. bronchiseptica in swine, we compared the abilities of a virulent swine isolate and an isogenic T3SS mutant to colonize, cause disease, and be transmitted from host to host. We found that the T3SS is required for maximal persistence throughout the lower swine respiratory tract and contributed significantly to the development of nasal lesions and pneumonia. However, the T3SS mutant and the wild-type parent are equally capable of transmission among swine by both direct and indirect routes, demonstrating that transmission can occur even with attenuated disease. Our data further suggest that the T3SS skews the adaptive immune response in swine by hindering the development of serum anti-Bordetella antibody levels and inducing an interleukin-10 (IL-10) cell-mediated response, likely contributing to the persistence of B. bronchiseptica in the respiratory tract. Overall, our results demonstrate that the Bordetella T3SS is required for maximal persistence and disease severity in pigs, but not for transmission.",,"['Nicholson, Tracy L.', 'Brockmeier, Susan L.', 'Loving, Crystal L.', 'Register, Karen B.', 'Kehrli, Marcus E.', 'Shore, Sarah M.']",,,,
,PMC,Antinociceptive Effects of Sustained-Release Buprenorphine in a Model of Incisional Pain in Rats (Rattus norvegicus),,PMC3966277,,,"Effective management of postoperative pain is an essential component of the care and welfare of laboratory animals. A sustained-release formulation of buprenorphine (Bup-SR) has recently been introduced to the veterinary market and has been reported to provide analgesia for as long as 72 h. Using evoked mechanical and thermal hypersensitivity tests, we here evaluated the antinociceptive effects of Bup-SR in a model of incisional pain in rats. Paw withdrawal responses were obtained before and 1 through 4 d after surgery. Rats are assigned to receive Bup-SR (0.3, 1.2, or 4.5 mg/kg SC once) or buprenorphine HCl (Bup HCl, 0.05 mg/kg SC twice daily for 3 d). Responses to mechanical and thermal stimuli in the 1.2 and 4.5 Bup-SR groups did not differ from those of rats in the Bup HCl group. Thermal latency on day 3 in rats that received 0.3 mg/kg Bup-SR was significantly different from baseline, indicating that this dose effectively decreased thermal hypersensitivity for at least 48 h. Marked sedation occurred in rats in the 4.5 Bup-SR group. Our findings indicate that Bup-SR at 0.3 or 1.2 mg/kg SC is effective in minimizing hypersensitivity with minimal sedation for at least 48 h (thermal hypersensitivity) and 72 h, respectively, in the incisional pain model in rats.",,"['Chum, Helen H', 'Jampachairsri, Katechan', 'McKeon, Gabriel P', 'Yeomans, David C', 'Pacharinsak, Cholawat', 'Felt, Stephen A']",,,,
,PMC,Detection and Characterization of Mycoplasma pneumoniae during an Outbreak of Respiratory Illness at a University,http://dx.doi.org/10.1128/JCM.02810-13,PMC3957776,,,"An outbreak at a university in Georgia was identified after 83 cases of probable pneumonia were reported among students. Respiratory specimens were obtained from 21 students for the outbreak investigation. The TaqMan array card (TAC), a quantitative PCR (qPCR)-based multipathogen detection technology, was used to initially identify Mycoplasma pneumoniae as the causative agent in this outbreak. TAC demonstrated 100% diagnostic specificity and sensitivity compared to those of the multiplex qPCR assay for this agent. All M. pneumoniae specimens (n = 12) and isolates (n = 10) were found through genetic analysis to be susceptible to macrolide antibiotics. The strain diversity of M. pneumoniae associated with this outbreak setting was identified using a variety of molecular typing procedures, resulting in two P1 genotypes (types 1 [60%] and 2 [40%]) and seven different multilocus variable-number tandem-repeat analysis (MLVA) profiles. Continued molecular typing of this organism, particularly during outbreaks, may enhance the current understanding of the epidemiology of M. pneumoniae and may ultimately lead to a more effective public health response.",,"['Waller, Jessica L.', 'Diaz, Maureen H.', 'Petrone, Brianna L.', 'Benitez, Alvaro J.', 'Wolff, Bernard J.', 'Edison, Laura', ""Tobin-D'Angelo, Melissa"", 'Moore, Ashley', 'Martyn, Audrey', 'Dishman, Hope', 'Drenzek, Cherie L.', 'Turner, Kim', 'Hicks, Lauri A.', 'Winchell, Jonas M.']",,,,
,PMC,High-Throughput Direct Fecal PCR Assay for Detection of Mycobacterium avium subsp. paratuberculosis in Sheep and Cattle,http://dx.doi.org/10.1128/JCM.03233-13,PMC3957769,,,"Johne's disease (JD) is a chronic enteric disease caused by Mycobacterium avium subsp. paratuberculosis that affects ruminants. Transmission occurs by the fecal-oral route. A commonly used antemortem diagnostic test for the detection of M. avium subsp. paratuberculosis in feces is liquid culture; however, a major constraint is the 2- to 3-month incubation period needed for this method. Rapid methods for the detection of M. avium subsp. paratuberculosis based on PCR have been reported, but comprehensive validation data are lacking. We describe here a new test, the high-throughput-Johnes (HT-J), to detect M. avium subsp. paratuberculosis in feces. Its diagnostic accuracy was compared with that of liquid radiometric (Bactec) fecal culture using samples from cattle (1,330 samples from 23 herds) and sheep (596 samples from 16 flocks). The multistage protocol involves the recovery of M. avium subsp. paratuberculosis cells from a fecal suspension, cell rupture by bead beating, extraction of DNA using magnetic beads, and IS900 quantitative PCR. The limit of detection of the assay was 0.0005 pg, and the limit of quantification was 0.005 pg M. avium subsp. paratuberculosis genomic DNA. Only M. avium subsp. paratuberculosis was detected from a panel of 51 mycobacterial isolates, including 10 with IS900-like sequences. Of the 549 culture-negative fecal samples from unexposed herds and flocks, 99% were negative in the HT-J test, while 60% of the bovine- and 84% of the ovine-culture-positive samples were positive in the HT-J test. As similar total numbers of samples from M. avium subsp. paratuberculosis-exposed animals were positive in culture and HT-J tests in both species, and as the results of a McNemar's test were not significant, these methods probably have similar sensitivities, but the true diagnostic sensitivities of these tests are unknown. These validation data meet the consensus-based reporting standards for diagnostic test accuracy studies for paratuberculosis and the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines (S. A. Bustin et al., Clin. Chem. 55:611–622, 2009, doi:10.1373/clinchem.2008.112797). The HT-J assay has been approved for use in JD control programs in Australia and New Zealand.",,"['Plain, Karren M.', 'Marsh, Ian B.', 'Waldron, Anna M.', 'Galea, Francesca', 'Whittington, Ann-Michele', 'Saunders, Vanessa F.', 'Begg, Douglas J.', 'de Silva, Kumudika', 'Purdie, Auriol C.', 'Whittington, Richard J.']",,,,
,PMC,Optimization of the extraction of total flavonoids from Scutellaria baicalensis Georgi using the response surface methodology,http://dx.doi.org/10.1007/s13197-014-1275-0,PMC4375232,,,"The response surface methodology (RSM) was used to optimize the conditions for total flavonoid extraction from Scutellaria baicalensis Georgi. The influences of the ethanol concentration, extraction time, temperature, and the liquid–solid ratio on flavonoid yield were investigated. Based on ANOVA results, a second-order quadratic polynomial model could be applied to characterize the extraction process. The following optimal extraction conditions were identified: ethanol concentration, 52.98 %; extraction time, 2.12 h; extraction temperature, 62.46 °C; and liquid–solid ratio, 35.23. The predicted extraction yield was 19.437 mg/g when these optimal conditions were used. The proposed method was successfully employed to extract flavonoids from S. baicalensis.",,"['Liu, Yanqing', 'Wang, Hongwu', 'Cai, Xuan']",,,,
,PMC,"Neutrophils are needed for an effective immune response against pulmonary rat coronavirus infection, but also contribute to pathology",http://dx.doi.org/10.1099/vir.0.061986-0,PMC4093780,,,"Polymorphonuclear neutrophils (PMN) infiltrate the respiratory tract early after viral infection and can contribute to both host defence and pathology. Coronaviruses are important causes of respiratory tract infections, ranging from mild to severe depending on the viral strain. This study evaluated the role of PMN during a non-fatal pulmonary coronavirus infection in the natural host. Rat coronavirus (RCoV) causes respiratory disease in adult rats, characterized by an early PMN response, viral replication and inflammatory lesions in the lungs, mild weight loss and effective resolution of infection. To determine their role during RCoV infection, PMN were depleted and the effects on disease progression, viral replication, inflammatory response and lung pathology were analysed. Compared with RCoV infection in control animals, PMN-depleted rats had worsened disease with weight loss, clinical signs, mortality and prolonged pulmonary viral replication. PMN-depleted animals had fewer macrophages and lymphocytes in the respiratory tract, corresponding to lower chemokine levels. Combined with in vitro experiments showing that PMN express cytokines and chemokines in response to RCoV-infected alveolar epithelial cells, these findings support a role for PMN in eliciting an inflammatory response to RCoV infection. Despite their critical role in the protection from severe disease, the presence of PMN was correlated with haemorrhagic lesions, epithelial barrier permeability and cellular inflammation in the lungs. This study demonstrated that while PMN are required for an effective antiviral response, they also contribute to lung pathology during RCoV infection.",,"['Haick, Anoria K.', 'Rzepka, Joanna P.', 'Brandon, Elizabeth', 'Balemba, Onesmo B.', 'Miura, Tanya A.']",,,,
,PMC,Increasing similarity in the dynamics of influenza in two adjacent subtropical Chinese cities following the relaxation of border restrictions,http://dx.doi.org/10.1099/vir.0.059998-0,PMC3929176,,,"The drivers of influenza seasonality remain heavily debated, especially in tropical/subtropical regions where influenza activity can peak in winter, during the rainy season, or remain constant throughout the year. We compared the epidemiological and evolutionary patterns of seasonal influenza epidemics in Hong Kong and Shenzhen, two adjacent cities in subtropical southern China. This comparison represents a unique natural experiment, as connectivity between these two cities has increased over the past decade. We found that, whilst summer influenza epidemics in Shenzhen used to peak 1–3 months later than those in Hong Kong, the difference decreased after 2005 (P<0.0001). Phylogenetic analysis revealed that influenza isolates from Shenzhen have become genetically closer to those circulating in Hong Kong over time (P = 0.045). Furthermore, although Shenzhen isolates used to be more distant from the global putative source of influenza viruses than isolates from Hong Kong (P<0.001), this difference has narrowed (P = 0.02). Overall, our study reveals that influenza activities show remarkably distinct epidemiological and evolutionary patterns in adjacent subtropical cities and suggests that human mobility patterns can play a major role in influenza dynamics in the subtropics.",,"['Tan, Yi', 'Lam, Tommy Tsan-Yuk', 'Wu, Chunli', 'Lee, Shui-shan', 'Viboud, Cécile', 'Zhang, Renli', 'Weinberger, Daniel M.']",,,,
,PMC,Interferon-β and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays,http://dx.doi.org/10.1099/vir.0.061911-0,PMC3929173,,,"The Middle East respiratory syndrome coronavirus (MERS-CoV) presents a novel emerging threat to public health worldwide. Several treatments for infected individuals have been suggested including IFN, ribavirin and passive immunotherapy with convalescent plasma. Administration of IFN-α2b and ribavirin has improved outcomes of MERS-CoV infection in rhesus macaques when administered within 8 h post-challenge. However, detailed and systematic evidence on the activity of other clinically available drugs is limited. Here we compared the susceptibility of MERS-CoV with different IFN products (IFN-α2b, IFN-γ, IFN-universal, IFN-α2a and IFN-β), as well as with two antivirals, ribavirin and mycophenolic acid (MPA), against MERS-CoV (Hu/Jordan-N3/2012) in vitro. Of all the IFNs tested, IFN-β showed the strongst inhibition of MERS-CoV in vitro, with an IC(50) of 1.37 U ml(−1), 41 times lower than the previously reported IC(50) (56.08 U ml(−1)) of IFN-α2b. IFN-β inhibition was confirmed in the virus yield reduction assay, with an IC(90) of 38.8 U ml(−1). Ribavirin did not inhibit viral replication in vitro at a dose that would be applicable to current treatment protocols in humans. In contrast, MPA showed strong inhibition, with an IC(50) of 2.87 µM. This drug has not been previously tested against MERS-CoV and may provide an alternative to ribavirin for treatment of MERS-CoV. In conclusion, IFN-β, MPA or a combination of the two may be beneficial in the treatment of MERS-CoV or as a post-exposure intervention in high-risk patients with known exposures to MERS-CoV.",,"['Hart, Brit J.', 'Dyall, Julie', 'Postnikova, Elena', 'Zhou, Huanying', 'Kindrachuk, Jason', 'Johnson, Reed F.', 'Olinger, Gene G.', 'Frieman, Matthew B.', 'Holbrook, Michael R.', 'Jahrling, Peter B.', 'Hensley, Lisa']",,,,
,PMC,The two faces of heterologous immunity: protection or immunopathology,http://dx.doi.org/10.1189/jlb.0713386,PMC3923083,,,"Immunity to previously encountered viruses can alter responses to unrelated pathogens. This phenomenon, which is known as heterologous immunity, has been well established in animal model systems. Heterologous immunity appears to be relatively common and may be beneficial by boosting protective responses. However, heterologous reactivity can also result in severe immunopathology. The key features that define heterologous immune modulation include alterations in the CD4(+) and CD8(+) T cell compartments and changes in viral dynamics and disease progression. In this review, we discuss recent advances and the current understanding of antiviral immunity in heterologous infections. The difficulties of studying these complex heterologous infections in humans are discussed, with special reference to the variations in HLA haplotypes and uncertainties about individuals' infection history. Despite these limitations, epidemiological analyses in humans and the data from mouse models of coinfection can be applied toward advancing the design of therapeutics and vaccination strategies.",,"['Sharma, Shalini', 'Thomas, Paul G.']",,,,
,PMC,Histone Deacetylase Inhibitors Potentiate Vesicular Stomatitis Virus Oncolysis in Prostate Cancer Cells by Modulating NF-κB-Dependent Autophagy,http://dx.doi.org/10.1128/JVI.03406-13,PMC3958113,,,"Vesicular stomatitis virus (VSV) is an oncolytic virus that induces cancer cell death through activation of the apoptotic pathway. Intrinsic resistance to oncolysis is found in some cell lines and many primary tumors as a consequence of residual innate immunity to VSV. In resistant-tumor models, VSV oncolytic potential can be reversibly stimulated by combination with epigenetic modulators, such as the histone deacetylase inhibitor vorinostat. Based on this reversible effect of vorinostat, we reasoned that critical host genes involved in oncolysis may likewise be reversibly regulated by vorinostat. A transcriptome analysis in prostate cancer PC3 cells identified a subset of NF-κB target genes reversibly regulated by vorinostat, as well as a group of interferon (IFN)-stimulated genes (ISGs). Consistent with the induction of NF-κB target genes, vorinostat-mediated enhancement of VSV oncolysis increased hyperacetylation of NF-κB RELA/p65. Additional bioinformatics analysis revealed that NF-κB signaling also increased the expression of several autophagy-related genes. Kinetically, autophagy preceded apoptosis, and apoptosis was observed only when cells were treated with both VSV and vorinostat. VSV replication and cell killing were suppressed when NF-κB signaling was inhibited using pharmacological or genetic approaches. Inhibition of autophagy by 3-methyladenine (3-MA) enhanced expression of ISGs, and either 3-MA treatment or genetic ablation of the autophagic marker Atg5 decreased VSV replication and oncolysis. Together, these data demonstrate that vorinostat stimulates NF-κB activity in a reversible manner via modulation of RELA/p65 signaling, leading to induction of autophagy, suppression of the IFN-mediated response, and subsequent enhancement of VSV replication and apoptosis.",,"['Shulak, Laura', 'Beljanski, Vladimir', 'Chiang, Cindy', 'Dutta, Sucharita M.', 'Van Grevenynghe, Julien', 'Belgnaoui, S. Mehdi', 'Nguyên, Thi Lien-Anh', 'Di Lenardo, Thomas', 'Semmes, O. John', 'Lin, Rongtuan', 'Hiscott, John']",,,,
,PMC,Characterization of Human Astrovirus Cell Entry,http://dx.doi.org/10.1128/JVI.02908-13,PMC3958088,,,"Human astroviruses (HAstV) are a frequent cause of gastroenteritis in young children and immunocompromised patients. To understand the early steps of HAstV infection in the highly permissive Caco-2 cell line, the binding and entry processes of the virus were characterized. The half-time of virus binding to the cell surface was about 10 min, while virus decapsidation took around 130 min. Drugs affecting clathrin-mediated endocytosis, endosome acidification, and actin filament polymerization, as well as those that reduce the presence of cholesterol in the cell membrane, decreased the infectivity of the virus. The infection was also reduced by silencing the expression of the clathrin heavy chain (CHC) by RNA interference or by overexpression of dominant-negative mutants of dynamin 2 and Eps15. Furthermore, the entry of HAstV apparently depends on the maturation of endosomes, since the infection was reduced by silencing the expression of Rab7, a small GTPase involved in the early- to late-endosome maturation. Altogether, our results suggest that HAstV enters Caco-2 cells using a clathrin-dependent pathway and reaches late endosomes to enter cells. Here, we have characterized the mechanism used by human astroviruses, important agents of gastroenteritis in children, to gain entry into their host cells. Using a combination of biochemical and genetic tools, we found that these viruses enter Caco-2 cells using a clathrin-dependent endocytic pathway, where they most likely need to travel to late endosomes to reach the cytoplasm and begin their replication cycle.",,"['Méndez, Ernesto', 'Muñoz-Yañez, Claudia', 'Sánchez-San Martín, Claudia', 'Aguirre-Crespo, Gabriela', 'Baños-Lara, M. del Rocio', 'Gutierrez, Michelle', 'Espinosa, Rafaela', 'Acevedo, Yunuén', 'Arias, Carlos F.', 'López, Susana']",,,,
,PMC,Mechanism of Neutralization of Herpes Simplex Virus by Antibodies Directed at the Fusion Domain of Glycoprotein B,http://dx.doi.org/10.1128/JVI.03200-13,PMC3958082,,,"Glycoprotein B (gB), the fusogen of herpes simplex virus (HSV), is a class III fusion protein with a trimeric ectodomain of known structure for the postfusion state. Seen by negative-staining electron microscopy, it presents as a rod with three lobes (base, middle, and crown). gB has four functional regions (FR), defined by the physical location of epitopes recognized by anti-gB neutralizing monoclonal antibodies (MAbs). Located in the base, FR1 contains two internal fusion loops (FLs) and is the site of gB-lipid interaction (the fusion domain). Many of the MAbs to FR1 are neutralizing, block cell-cell fusion, and prevent the association of gB with lipid, suggesting that these MAbs affect FL function. Here we characterize FR1 epitopes by using electron microscopy to visualize purified Fab-gB ectodomain complexes, thus confirming the locations of several epitopes and localizing those of MAbs DL16 and SS63. We also generated MAb-resistant viruses in order to localize the SS55 epitope precisely. Because none of the epitopes of our anti-FR1 MAbs mapped to the FLs, we hyperimmunized rabbits with FL1 or FL2 peptides to generate polyclonal antibodies (PAbs). While the anti-FL1 PAb failed to bind gB, the anti-FL2 PAb had neutralizing activity, implying that the FLs become exposed during virus entry. Unexpectedly, the anti-FL2 PAb (and the anti-FR1 MAbs) bound to liposome-associated gB, suggesting that their epitopes are accessible even when the FLs engage lipid. These studies provide possible mechanisms of action for HSV neutralization and insight into how gB FR1 contributes to viral fusion. IMPORTANCE For herpesviruses, such as HSV, entry into a target cell involves transfer of the capsid-encased genome of the virus to the target cell after fusion of the lipid envelope of the virus with a lipid membrane of the host. Virus-encoded glycoproteins in the envelope are responsible for fusion. Antibodies to these glycoproteins are important biological tools, providing a way of examining how fusion works. Here we used electron microscopy and other techniques to study a panel of anti-gB antibodies. Some, with virus-neutralizing activity, impair gB-lipid association. We also generated a peptide antibody against one of the gB fusion loops; its properties provide insight into the way the fusion loops function as gB transits from its prefusion form to an active fusogen.",,"['Cairns, Tina M.', 'Fontana, Juan', 'Huang, Zhen-Yu', 'Whitbeck, J. Charles', 'Atanasiu, Doina', 'Rao, Samhita', 'Shelly, Spencer S.', 'Lou, Huan', 'Ponce de Leon, Manuel', 'Steven, Alasdair C.', 'Eisenberg, Roselyn J.', 'Cohen, Gary H.']",,,,
,PMC,Diverse Recombinant HIV-1 Envs Fail To Activate B Cells Expressing the Germline B Cell Receptors of the Broadly Neutralizing Anti-HIV-1 Antibodies PG9 and 447-52D,http://dx.doi.org/10.1128/JVI.03228-13,PMC3958080,,,"Broadly neutralizing antibodies (bNAbs) against HIV-1 are generated during HIV-1-infection but have not yet been elicited by immunization with recombinant forms of the viral envelope glycoprotein (Env; the target of anti-HIV-1 neutralizing antibodies). A particular type of bNAb targets the CD4-binding site (CD4-BS) region of Env. These antibodies are derived from a limited number of VH/VL genes and can bind to and neutralize diverse HIV-1 strains. Recent reports have demonstrated the limited potential of Env to activate B cells expressing the germline B cell receptor (BCR) forms of anti-CD4-BS bNAbs. A potential reason for the lack of elicitation of anti-CD4-BS bNAbs by Env immunogens is the absence of stimulation of naive B cells expressing the germline BCRs of such antibodies. Several bNAbs have been isolated from HIV-1-infected subjects that target other structurally conserved regions of Env. How frequently Env immunogens stimulate the germline BCRs that give rise to bNAbs that target Env regions other than the CD4-BS is not well understood. Here, we investigated the interactions between diverse Envs and the BCRs of known bNAbs targeting not only the CD4-BS but also conserved elements of the second and third variable Env regions. Our results indicate that Env is generally ineffective in engaging germline BCRs of bNAbs irrespective of their epitope target. Potentially, this is the result of viral evolutionary mechanisms adopted to escape broadly neutralizing antibody responses. Our results also suggest that a single Env capable of activating germline BCRs that target distinct Env epitopes will be very difficult to identify or to design. IMPORTANCE Broadly neutralizing antibodies against HIV-1 are thought to be an important component of the immune responses that a successful vaccine should elicit. Broadly neutralizing antibodies are generated by a subset of those infected by HIV-1, but so far, they have not been generated by immunization with recombinant Envelope (Env, the target of anti-HIV-1 neutralizing antibodies). Here, we provide evidence that the inability of Env to elicit the production of broadly neutralizing antibodies is due to the inability of diverse Envs to engage the germline B cell receptor forms of known broadly neutralizing antibodies.",,"['McGuire, Andrew T.', 'Glenn, Jolene A.', 'Lippy, Adriana', 'Stamatatos, Leonidas']",,,,
,PMC,Effect of Microtubule Disruption on Neuronal Spread and Replication of Demyelinating and Nondemyelinating Strains of Mouse Hepatitis Virus In Vitro,http://dx.doi.org/10.1128/JVI.02545-13,PMC3958069,,,"The isogenic host attachment spike protein recombinant demyelinating strain of mouse hepatitis virus (MHV) (RSA59) and the nondemyelinating strain (RSMHV2) differ in their abilities to infect distinct types of neural cells, spread from cell to cell, and induce subsequent demyelination and axonal loss. The differential demyelination properties of RSA59 and RSMHV2 may be a function of spike protein-mediated neuronal transport. Disruption of microtubules with colchicine and vinblastine significantly blocks neuronal transport and reduces the replication of RSA59, whereas RSMHV2 remains unaffected.",,"['Biswas, Kaushiki', 'Das Sarma, Jayasri']",,,,
,PMC,mRNA Cap Methylation Influences Pathogenesis of Vesicular Stomatitis Virus In Vivo,http://dx.doi.org/10.1128/JVI.03420-13,PMC3958058,,,"One role of mRNA cap guanine-N-7 (G-N-7) methylation is to facilitate the efficient translation of mRNA. The role of mRNA cap ribose 2′-O methylation is enigmatic, although recent work has implicated this as a signature to avoid detection of RNA by the innate immune system (S. Daffis, K. J. Szretter, J. Schriewer, J. Q. Li, S. Youn, J. Errett, T. Y. Lin, S. Schneller, R. Zust, H. P. Dong, V. Thiel, G. C. Sen, V. Fensterl, W. B. Klimstra, T. C. Pierson, R. M. Buller, M. Gale, P. Y. Shi, M. S. Diamond, Nature 468:452-456, 2010, doi:10.1038/nature09489). Working with vesicular stomatitis virus (VSV), we previously showed that a panel of recombinant VSVs carrying mutations at a predicted methyltransferase catalytic site (rVSV-K1651A, -D1762A, and -E1833Q) or S-adenosylmethionine (SAM) binding site (rVSV-G1670A, -G1672A, and -G4A) were defective in cap methylation and were also attenuated for growth in cell culture. Here, we analyzed the virulence of these recombinants in mice. We found that rVSV-K1651A, -D1762A, and -E1833Q, which are defective in both G-N-7 and 2′-O methylation, were highly attenuated in mice. All three viruses elicited a high level of neutralizing antibody and provided full protection against challenge with the virulent VSV. In contrast, mice inoculated with rVSV-G1670A and -G1672A, which are defective only in G-N-7 methylation, were attenuated in vivo yet retained a low level of virulence. rVSV-G4A, which is completely defective in both G-N-7 and 2′-O methylation, also exhibited low virulence in mice despite the fact that productive viral replication was not detected in lung and brain. Taken together, our results suggest that abrogation of viral mRNA cap methylation can serve as an approach to attenuate VSV, and perhaps other nonsegmented negative-strand RNA viruses, for potential application as vaccines and viral vectors. IMPORTANCE Nonsegmented negative-sense (NNS) RNA viruses include a wide range of significant human, animal, and plant pathogens. For many of these viruses, there are no vaccines or antiviral drugs available. mRNA cap methylation is essential for mRNA stability and efficient translation. Our current understanding of mRNA modifications of NNS RNA viruses comes largely from studies of vesicular stomatitis virus (VSV). In this study, we showed that recombinant VSVs (rVSVs) defective in mRNA cap methylation were attenuated in vitro and in vivo. In addition, these methyltransferase (MTase)-defective rVSVs triggered high levels of antibody responses and provided complete protection against VSV infection. Thus, this study will not only contribute to our understanding of the role of mRNA cap MTase in viral pathogenesis but also facilitate the development of new live attenuated vaccines for VSV, and perhaps other NNS RNA viruses, by inhibiting viral mRNA cap methylation.",,"['Ma, Yuanmei', 'Wei, Yongwei', 'Zhang, Xiaodong', 'Zhang, Yu', 'Cai, Hui', 'Zhu, Yang', 'Shilo, Konstantin', 'Oglesbee, Michael', 'Krakowka, Steven', 'Whelan, Sean P. J.', 'Li, Jianrong']",,,,
,PMC,Evasion of Antiviral Immunity through Sequestering of TBK1/IKKε/IRF3 into Viral Inclusion Bodies,http://dx.doi.org/10.1128/JVI.03510-13,PMC3957960,,,"Cells are equipped with pattern recognition receptors (PRRs) such as the Toll-like and RIG-I-like receptors that mount innate defenses against viruses. However, viruses have evolved multiple strategies to evade or thwart host antiviral responses. Viral inclusion bodies (IBs), which are accumulated aggregates of viral proteins, are commonly formed during the replication of some viruses in infected cells, but their role in viral immune evasion has rarely been explored. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging febrile illness caused by a novel phlebovirus in the Bunyaviridae. The SFTS viral nonstructural protein NSs can suppress host beta interferon (IFN-β) responses. NSs can form IBs in infected and transfected cells. Through interaction with tank-binding kinase 1 (TBK1), viral NSs was able to sequester the IKK complex, including IKKε and IRF3, into IBs, although NSs did not interact with IKKε or IRF3 directly. When cells were infected with influenza A virus, IRF3 was phosphorylated and active phosphorylated IRF3 (p-IRF3) was translocated into the nucleus. In the presence of NSs, IRF3 could still be phosphorylated, but p-IRF3 was trapped in cytoplasmic IBs, resulting in reduced IFN-β induction and enhanced viral replication. Sequestration of the IKK complex and active IRF3 into viral IBs through the interaction of NSs and TBK1 is a novel mechanism for viral evasion of innate immunity.",,"['Wu, Xiaodong', 'Qi, Xian', 'Qu, Bingqian', 'Zhang, Zerui', 'Liang, Mifang', 'Li, Chuan', 'Cardona, Carol J.', 'Li, Dexin', 'Xing, Zheng']",,,,
,PMC,"H1N1, but Not H3N2, Influenza A Virus Infection Protects Ferrets from H5N1 Encephalitis",http://dx.doi.org/10.1128/JVI.01840-13,PMC3957958,,,"Seasonal influenza causes substantial morbidity and mortality because of efficient human-to-human spread. Rarely, zoonotic strains of influenza virus spread to humans, where they have the potential to mediate new pandemics with high mortality. We studied systemic viral spread after intranasal infection with highly pathogenic avian influenza virus (H5N1 [A/Viet Nam/1203/2004]) in ferrets with or without prior pandemic H1N1pdm09 (A/Mexico/4108/2009) or H3N2 (A/Victoria/361/2011) infection. After intranasal challenge with H5N1 influenza virus, naive ferrets rapidly succumbed to systemic infection. Animals challenged with H5N1 influenza virus greater than 3 months after recovering from an initial H1N1pdm09 infection survived H5N1 virus challenge and cleared virus from the respiratory tract 4 days after infection. However, a prolonged low-level infection of hematopoietic elements in the small bowel lamina propria, liver, and spleen was present for greater than 2 weeks postinfection, raising the potential for reassortment of influenza genes in a host infected with multiple strains of influenza. Animals previously infected with an H3N2 influenza virus succumbed to systemic disease and encephalitis after H5N1 virus challenge. These results indicate prior infection with different seasonal influenza strains leads to radically different protection from H5N1 challenge and fatal encephalitis. IMPORTANCE Seasonal influenza is efficiently transmitted from human to human, causing substantial morbidity and mortality. Rarely, zoonotic strains of influenza virus spread to humans, where they have the potential to mediate new pandemics with high mortality. Infection of naive ferrets with H5N1 avian influenza virus causes a rapid and lethal systemic disease. We studied systemic H5N1 viral spread after infection of ferrets with or without prior exposure to either of two seasonal influenza virus strains, H1N1 and H3N2. Ferrets previously infected with H1N1 survive H5N1 challenge while those previously infected with H3N2 die of encephalitis. However ferrets protected from lethal H5N1 infection develop persistent low-level infection of the small intestine, liver, or spleen, providing a nidus for future viral strain recombination. The mechanism by which prior infection with specific strains of seasonal influenza virus protect from lethal H5N1 challenge needs to be elucidated in order to design effective immunization and treatments.",,"['Bissel, Stephanie J.', 'Wang, Guoji', 'Carter, Donald M.', 'Crevar, Corey J.', 'Ross, Ted M.', 'Wiley, Clayton A.']",,,,
,PMC,Analysis of ORF5 and Full-Length Genome Sequences of Porcine Reproductive and Respiratory Syndrome Virus Isolates of Genotypes 1 and 2 Retrieved Worldwide Provides Evidence that Recombination Is a Common Phenomenon and May Produce Mosaic Isolates,http://dx.doi.org/10.1128/JVI.02858-13,PMC3957927,,,"Recombination is currently recognized as a factor for high genetic diversity, but the frequency of such recombination events and the genome segments involved are not well known. In the present study, we initially focused on the detection of recombinant porcine reproductive and respiratory syndrome virus (PRRSV) isolates by examining previously published data sets of ORF5 sequences (genotypes 1 and 2) obtained worldwide. We then examined full-length genome sequences in order to determine potential recombination breakpoints along the viral genome. For ORF5, 11 sets of genotype 1 sequences from different geographical areas, including 2 Asian, 1 American, and 7 European regions, and three sets of genotype 2, including sets from China, Mexico, and the United States, were analyzed separately. Potential recombination breakpoints were detected in 10/11 genotype 1 sets, including 9 cases in which the clustering of at least one isolate was different before and after the breakpoints. In genotype 2, potential breakpoints and different tree clustering of at least one strain before and after the breakpoint were observed in 2 out of 3 sets. The results indicated that most of the ORF5 data sets contained at least one recombinant sequence. When the full-length genome sequences were examined, both genotype 1 and 2 sets presented breakpoints (10 and 9, respectively), resulting in significantly different topologies before and after the breakpoints. Mosaic genomes were detected in genotype 1 sequences. These results may have significant implications for the understanding of the molecular epidemiology of PRRSV. IMPORTANCE PRRSV is one of the most important viruses affecting swine production worldwide, causing big economic losses and sanitary problems. One of the key questions on PRRSV arises from its genetic diversity, which is thought to have a direct impact on immunobiology, epidemiology, diagnosis, and vaccine efficacy. One of the causes of this genetic diversity is recombination among strains. This study provides evidence that recombinant PRRSV isolates are common in most of the countries with significant swine production, especially PRRSV genotype 1. This observation has implications in the proper characterization of PRRSV strains, in the future development of phylogenetic studies, and in the development of new PRRSV control strategies. Moreover, the present paper emphasizes the need for a deeper understanding of the mechanisms and circumstances involved in the generation of genetic diversity of PRRSV.",,"['Martín-Valls, G. E.', 'Kvisgaard, L. K.', 'Tello, M.', 'Darwich, L.', 'Cortey, M.', 'Burgara-Estrella, A. J.', 'Hernández, J.', 'Larsen, L. E.', 'Mateu, E.']",,,,
,PMC,Enterovirus 2A(pro) Targets MDA5 and MAVS in Infected Cells,http://dx.doi.org/10.1128/JVI.02712-13,PMC3957915,,,"RIG-I-like receptors (RLRs) MDA5 and RIG-I are key players in the innate antiviral response. Upon recognition of viral RNA, they interact with MAVS, eventually inducing type I interferon production. The interferon induction pathway is commonly targeted by viruses. How enteroviruses suppress interferon production is incompletely understood. MDA5 has been suggested to undergo caspase- and proteasome-mediated degradation during poliovirus infection. Additionally, MAVS is reported to be cleaved during infection with coxsackievirus B3 (CVB3) by the CVB3 proteinase 3C(pro), whereas MAVS cleavage by enterovirus 71 has been attributed to 2A(pro). As yet, a detailed examination of the RLR pathway as a whole during any enterovirus infection is lacking. We performed a comprehensive analysis of crucial factors of the RLR pathway, including MDA5, RIG-I, LGP2, MAVS, TBK1, and IRF3, during infection of CVB3, a human enterovirus B (HEV-B) species member. We show that CVB3 inhibits the RLR pathway upstream of TBK1 activation, as demonstrated by limited phosphorylation of TBK1 and a lack of IRF3 phosphorylation. Furthermore, we show that MDA5, MAVS, and RIG-I all undergo proteolytic degradation in CVB3-infected cells through a caspase- and proteasome-independent manner. We convincingly show that MDA5 and MAVS cleavages are both mediated by CVB3 2A(pro), while RIG-I is cleaved by 3C(pro). Moreover, we show that proteinases 2A(pro) and 3C(pro) of poliovirus (HEV-C) and enterovirus 71 (HEV-A) exert the same functions. This study identifies a critical role of 2A(pro) by cleaving MDA5 and MAVS and shows that enteroviruses use a common strategy to counteract the interferon response in infected cells. IMPORTANCE Human enteroviruses (HEVs) are important pathogens that cause a variety of diseases in humans, including poliomyelitis, hand, foot, and mouth disease, viral meningitis, cardiomyopathy, and more. Like many other viruses, enteroviruses target the host immune pathways to gain replication advantage. The MDA5/MAVS pathway is responsible for recognizing enterovirus infections in the host cell and leads to expression of type I interferons (IFN-I), crucial antiviral signaling molecules. Here we show that three species of HEVs all employ the viral proteinase 2A (2A(pro)) to proteolytically target MDA5 and MAVS, leading to an efficient blockade upstream of IFN-I transcription. These observations suggest that MDA5/MAVS antagonization is an evolutionarily conserved and beneficial mechanism of enteroviruses. Understanding the molecular mechanisms of enterovirus immune evasion strategies will help to develop countermeasures to control infections with these viruses in the future.",,"['Feng, Qian', 'Langereis, Martijn A.', 'Lork, Marie', 'Nguyen, Mai', 'Hato, Stanleyson V.', 'Lanke, Kjerstin', 'Emdad, Luni', 'Bhoopathi, Praveen', 'Fisher, Paul B.', 'Lloyd, Richard E.', 'van Kuppeveld, Frank J. M.']",,,,
,PMC,The use of facemasks to prevent respiratory infection: a literature review in the context of the Health Belief Model,http://dx.doi.org/10.11622/smedj.2014037,PMC4293989,,,"INTRODUCTION: Acute respiratory infections are prevalent and pose a constant threat to society. While the use of facemasks has proven to be an effective barrier to curb the aerosol spread of such diseases, its use in the local community is uncommon, resulting in doubts being cast on its effectiveness in preventing airborne infections during epidemics. We thus aimed to conduct a literature review to determine the factors that influence the use of facemasks as a primary preventive health measure in the community. METHODS: A search for publications relating to facemask usage was performed on Medline, PubMed, Google, World Health Organization and Singapore government agencies’ websites, using search terms such as ‘facemask’, ‘mask’, ‘influenza’, ‘respiratory infection’, ‘personal protective equipment’, ‘disease prevention’, ‘compliance’ and ‘adherence’. Findings were framed under five components of the Health Belief Model perceived susceptibility, perceived benefits, perceived severity, perceived barriers and cues to action. RESULTS: We found that individuals are more likely to wear facemasks due to the perceived susceptibility and perceived severity of being afflicted with life-threatening diseases. Although perceived susceptibility appeared to be the most significant factor determining compliance, perceived benefits of mask-wearing was found to have significant effects on mask-wearing compliance as well. Perceived barriers include experience or perception of personal discomfort and sense of embarrassment. Media blitz and public health promotion activities supported by government agencies provide cues to increase the public’s usage of facemasks. CONCLUSION: Complex interventions that use multipronged approaches targeting the five components of the Health Belief Model, especially perceived susceptibility, are needed to increase the use of facemasks in the community. Further studies are required to evaluate the effectiveness of implemented interventions.",,"['Sim, Shin Wei', 'Moey, Kirm Seng Peter', 'Tan, Ngiap Chuan']",,,,
,PMC,Ten year retrospective evaluation of the seasonal distribution of agent viruses in childhood respiratory tract infections,http://dx.doi.org/10.5152/tpa.2014.1121,PMC4462269,,,"AIM: Infections caused by respiratory viruses sometimes occur as epidemias or pandemias and are an important public health problem in the whole world. These viral agents may lead to severe respiratory diseases especially in young children and in the elderly. The aim of this study was to determine the seasonal distribution of agent viruses in childhood respiratory infections in our region. MATERIAL AND METHODS: In this study, nasopharyngeal swab sample was obtained from 1 326 patients who presented to Ege University, Medical Faculty Children’s Hospital between 2002 and 2012 and who were thought to have respiratory tract infection. Influenza virus type A and B, respiratory syncytial virus, adenovirus and parainfluenza virus type 1–3 were investigated using shell-vial cell culture method and direct fluorescent antibody test and/or multiplex PCR test. Parainfluenza virus type 4, human metapneumovirus, rhinovirus, coronavirus, human bocavirus were investigated using multiplex PCR test. The seasonal distributions of the viruses were determined according to the results obtained from Ege University Medical Faculty, Department of Medical Microbiology Clinical Virology Laboratory. Approval was obtained from the ethics committee (Ege University Clinical Researches Ethics Committee, 12.02.2013, number: 13–1/46). RESULTS: The majority of the patients who presented were outpatients (n:888, 67%) and the remainder were hospitalized patients (33%, n:438). Respiratory viruses were found in 503 of the nasopharyngeal swab samples (38%). Parainfluenza and respiratory syncytial virus were found most frequently in December–february (58% and 59%, respectively, influenza viruses were found most frequently in November–december (72%) and adenoviruses were found most frequently in may–september (56%). CONCLUSION: Although only supportive therapies are administered generally in viral infections, viral investigations are important in terms of determining the measures to be taken by determining the causes as well as in terms of establishing a general database. Another benefit of this study would be strengthening clinical approach to patients and decreasing unnecessary antibiotic use.",,"['Gülen, Figen', 'Yıldız, Başak', 'Çiçek, Candan', 'Demir, Esen', 'Tanaç, Remziye']",,,,
,PMC,MERS: emergence of a novel human coronavirus,http://dx.doi.org/10.1016/j.coviro.2014.01.010,PMC4028407,,,"A novel coronavirus (CoV) that causes a severe lower respiratory tract infection in humans, emerged in the Middle East region in 2012. This virus, named Middle East respiratory syndrome (MERS)-CoV, is phylogenetically related to bat CoVs, but other animal species like dromedary camels may potentially act as intermediate hosts by spreading the virus to humans. Although human to human transmission has been demonstrated, analysis of human MERS clusters indicated that chains of transmission were not self-sustaining, especially when infection control was implemented. Thus, timely identification of new MERS cases followed by their quarantine, combined with measures to limit spread of the virus from the (intermediate) host to humans, may be crucial in controlling the outbreak of this emerging CoV.",,"['Raj, V. Stalin', 'Osterhaus, Albert D.M.E.', 'Fouchier, Ron A.M.', 'Haagmans, Bart L.']",,,,
,PMC,Outbreak Column 13: Nosocomial Staphylococcus aureus outbreaks (part 2 – guidelines),http://dx.doi.org/10.1177/1757177414520815,PMC5074123,,,,,"Curran, Evonne T",,,,
,PMC,Mapping the innate signaling cascade essential for cytokine storm during influenza virus infection,http://dx.doi.org/10.1073/pnas.1400593111,PMC3956176,,,"During pathogenic influenza virus infection, robust cytokine production (cytokine storm), excessive inflammatory infiltrates, and virus-induced tissue destruction all contribute to morbidity and mortality. Earlier we reported that modulation of sphingosine-1-phosphate-1 receptor (S1P(1)R) signaling provided a chemically tractable approach for the effective blunting of cytokine storm, leading to the improvement of clinical and survival outcomes. Here, we show that S1P(1)R agonist treatment suppresses global cytokine amplification. Importantly, S1P(1)R agonist treatment was able to blunt cytokine/chemokine production and innate immune cell recruitment in the lung independently of endosomal and cytosolic innate sensing pathways. S1P(1)R signaling suppression of cytokine amplification was independent of multiple innate signaling adaptor pathways for myeloid differentiation primary response gene 88 (MyD88) and IFN-β promoter stimulator-1 signaling, indicating a common pathway inhibition of cytokine storm. We identify the MyD88 adaptor molecule as responsible for the majority of cytokine amplification observed following influenza virus challenge.",,"['Teijaro, John R.', 'Walsh, Kevin B.', 'Rice, Stephanie', 'Rosen, Hugh', 'Oldstone, Michael B. A.']",,,,
,PMC,Systems biology unravels interferon responses to respiratory virus infections,http://dx.doi.org/10.4331/wjbc.v5.i1.12,PMC3942539,,,"Interferon production is an important defence against viral replication and its activation is an attractive therapeutic target. However, it has long been known that viruses perpetually evolve a multitude of strategies to evade these host immune responses. In recent years there has been an explosion of information on virus-induced alterations of the host immune response that have resulted from data-rich omics technologies. Unravelling how these systems interact and determining the overall outcome of the host response to viral infection will play an important role in future treatment and vaccine development. In this review we focus primarily on the interferon pathway and its regulation as well as mechanisms by which respiratory RNA viruses interfere with its signalling capacity.",,"['Kroeker, Andrea L', 'Coombs, Kevin M']",,,,
,PMC,Protective and Detrimental Roles for Regulatory T Cells in a Viral Model for Multiple Sclerosis,http://dx.doi.org/10.1111/bpa.12119,PMC4097993,,,"Multiple sclerosis (MS) has been proposed to be an immune-mediated disease in the central nervous system (CNS) that can be triggered by virus infections. In Theiler’s murine encephalomyelitis virus (TMEV) infection, during the first week (acute stage), mice develop polioencephalomyelitis. After 3 weeks (chronic stage), mice develop immune-mediated demyelination with virus persistence, which has been used as a viral model for MS. Regulatory T cells (Tregs) can suppress inflammation, and have been suggested to be protective in immune-mediated diseases, including MS. However, in virus-induced inflammatory demyelination, although Tregs can suppress inflammation, preventing immune-mediated pathology, Tregs may also suppress anti-viral immune responses, leading to more active viral replication and/or persistence. To determine the role and potential translational usage of Tregs in MS, we treated TMEV-infected mice with ex vivo-generated induced Tregs (iTregs) on day 0 (early) or during the chronic stage (therapeutic). Early treatment worsened clinical signs during acute disease. The exacerbation of acute disease was associated with increased virus titers and decreased immune cell recruitment in the CNS. Therapeutic iTreg treatment reduced inflammatory demyelination during chronic disease. Immunologically, iTreg treatment increased interleukin-10 production from B cells, CD4(+) T cells, and dendritic cells, which may contribute to the decreased CNS inflammation.",,"['Martinez, Nicholas E.', 'Karlsson, Fridrik', 'Sato, Fumitaka', 'Kawai, Eiichiro', 'Omura, Seiichi', 'Minagar, Alireza', 'Grisham, Matthew. B.', 'Tsunoda, Ikuo']",,,,
,PMC,Glyco-epitope Diversity: An Evolving Area of Glycomics Research and Biomarker Discovery,http://dx.doi.org/10.4172/jpb.10000e24,PMC4219575,,,,,"Wang, Denong",,,,
,PMC,Lack of Group X Secreted Phospholipase A(2) Increases Survival Following Pandemic H1N1 Influenza Infection,http://dx.doi.org/10.1016/j.virol.2014.01.030,PMC4106042,,,"The role of Group X secreted phospholipase A(2) (GX-sPLA(2)) during influenza infection has not been previously investigated. We examined the role of (Reviewer 2 Minor Comment 2) GX-sPLA(2) during H1N1 pandemic influenza infection in a GX-sPLA(2) gene targeted mouse (GX(−/−)) model and found that survival after infection was significantly greater in GX(−/−) mice than in GX(+/+) mice. Downstream products of GX-sPLA(2) activity, PGD(2), PGE(2), LTB(4), cysteinyl leukotrienes and Lipoxin A(4) were significantly lower in GX(−/−) mice BAL fluid. Lung microarray analysis identified an earlier and more robust induction of T and B cell associated genes in GX(−/−) mice. Based on the central role of sPLA(2) enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA(2) during H1N1pdm infection is an early step of pulmonary inflammation and its (Reviewer 2 Minor Comment 2) inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA(2) may be a potential therapeutic target during influenza.",,"['Kelvin, Alyson A.', 'Degousee, Norbert', 'Banner, David', 'Stefanski, Eva', 'Leon, Alberto J.', 'Angoulvant, Denis', 'Paquette, Stéphane G.', 'Huang, Stephen S. H.', 'Danesh, Ali', 'Robbins, Clinton S.', 'Noyan, Hossein', 'Husain, Mansoor', 'Lambeau, Gerard', 'Gelb, Michael H.', 'Kelvin, David J.', 'Rubin, Barry B.']",,,,
,PMC,"A case-control study evaluating RT-PCR/ESI-MS technology compared to direct fluorescent antibody and xTAG RVP PCR,,",http://dx.doi.org/10.1016/j.diagmicrobio.2014.02.009,PMC4557781,,,"Waste nasopharyngeal swabs (N = 244) were evaluated by the reverse-transcriptase polymerase chain reaction/electrospray ionization mass spectrometry PLEX-ID Broad Respiratory Virus Surveillance Kit version 2.5 compared to direct fluorescent antibody and xTAG Respiratory Virus Panel for percent agreement, sensitivity, and specificity. Sensitivity and specificity were 91% (111/122) and 95.1% (116/122), respectively. Sensitivity by virus, except parainfluenza, was 92.9–100%, and specificity was 99–100%.",,"['Hardick, Justin', 'Sadiq, Sufyan', 'Perelstein, Elizabeth', 'Peterson, Stephen', 'Rothman, Richard', 'Gaydos, Charlotte A.']",,,,
,PMC,A novel membrane fusion protein family in Flaviviridae?,http://dx.doi.org/10.1016/j.tim.2014.01.008,PMC3985287,,,"Enveloped viruses must fuse their lipid membrane to a cellular membrane to deliver their genome into the cytoplasm for replication. Viral envelope proteins catalyze this critical membrane fusion event. They fall into three distinct structural classes. In 2013, envelope proteins from a pestivirus and hepatitis C virus were found to have two distinct novel folds. This was unexpected because these viruses are in the same family as flaviviruses, which have class II fusion proteins. We propose that the membrane fusion machinery of the closely related pestiviruses and hepatitis C virus defines a new structural class. This and other recently identified structural relationships between viral fusion proteins shift the paradigm for how these proteins evolved.",,"['Li, Yue', 'Modis, Yorgo']",,,,
,PMC,Advances in Swine Immunology Help Move Vaccine Technology Forward,http://dx.doi.org/10.1016/j.vetimm.2014.02.017,PMC4107305,,,"In veterinary animal species, vaccines are the primary tool for disease prevention, a key tool for treatment of infection, and essential for helping maintain animal welfare and productivity. Traditional vaccine development by trial-and-error has achieved many successes. However, effective vaccines that provide solid cross-protective immunity with excellent safety are still needed for many diseases. The path to development of vaccines against difficult pathogens requires recognition of uniquely evolved immunological interactions of individual animal hosts and their specific pathogens. Here, general principles that currently guide veterinary immunology and vaccinology research are reviewed, with an emphasis on examples from swine. Advances in genomics and proteomics now provide the community with powerful tools for elucidation of regulatory and effector mechanisms of protective immunity that provide new opportunities for successful translation of immunological discoveries into safe and effective vaccines.",,"Murtaugh, Michael P.",,,,
,PMC,HIV-1 Mutates to Evade IFITM1 Restriction,http://dx.doi.org/10.1016/j.virol.2014.01.020,PMC4274668,,,"Interferon-induced transmembrane (IFITM) proteins inhibit the infection of a wide range of viruses including human immunodeficiency virus type 1 (HIV-1). At present, little is known about how viruses overcome IFITM restriction. In this study, we have utilized HIV-1 as a model and selected IFITM1-resistant viruses after multiple passages of HIV-1 in IFITM1-expressing SupT1 cells. Sequencing the entire viral genome revealed several mutations in the vpu and envelope genes, among which mutations Vpu34 and EnvG367E together enable efficient HIV-1 replication in IFITM1-expressing cells. Vpu34 introduces a stop codon at amino acid position 35 of Vpu, whereas EnvG367E changes the G367 residue at the CD4-binding site of gpl20. These two mutations do not appear to overcome the downregulation of viral p24 expression caused by IFITM1, but rather enhance HIV-1 replication by promoting cell-to-cell virus transmission. Altogether, our data demonstrate that HIV-1 can mutate to evade IFITM1 restriction by increasing cell-to-cell transmission.",,"['Ding, Shilei', 'Pan, Qinghua', 'Liu, Shan-Lu', 'Liang, Chen']",,,,
,PMC,Enteric viruses in turkey enteritis,http://dx.doi.org/10.1007/s13337-014-0198-8,PMC4188183,,,"Gut health is very important to get maximum returns in terms of weight gain and egg production. Enteric diseases such as poult enteritis complex (PEC) in turkeys do not allow their production potential to be achieved to its maximum. A number of viruses, bacteria, and protozoa have been implicated but the primary etiology has not been definitively established. Previously, electron microscopy was used to detect the presence of enteric viruses, which were identified solely on the basis of their morphology. With the advent of rapid molecular diagnostic methods and next generation nucleic acid sequencing, researchers have made long strides in identification and characterization of viruses associated with PEC. The molecular techniques have also helped us in identification of pathogens which were previously not known. Regional and national surveys have revealed the presence of several different enteric viruses in PEC including rotavirus, astrovirus, reovirus and coronavirus either alone or in combination. There may still be unknown pathogens that may directly or indirectly play a role in enteritis in turkeys. This review will focus on the role of turkey coronavirus, rotavirus, reovirus, and astrovirus in turkey enteritis.",,"['Jindal, Naresh', 'Mor, Sunil K.', 'Goyal, Sagar M.']",,,,
,PMC,Intranasal vaccination with recombinant receptor-binding domain of MERS-CoV spike protein induces much stronger local mucosal immune responses than subcutaneous immunization: Implication for designing novel mucosal MERS vaccines,http://dx.doi.org/10.1016/j.vaccine.2014.02.004,PMC4194189,,,"Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was originally identified in Saudi Arabia in 2012. It has caused MERS outbreaks with high mortality in the Middle East and Europe, raising a serious concern about its pandemic potential. Therefore, development of effective vaccines is crucial for preventing its further spread and future pandemic. Our previous study has shown that subcutaneous (s.c.) vaccination of a recombinant protein containing receptor-binding domain (RBD) of MERS-CoV S fused with Fc of human IgG (RBD-Fc) induced strong systemic neutralizing antibody responses in vaccinated mice. Here, we compared local and systemic immune responses induced by RBD-Fc via intranasal (i.n.) and s.c. immunization pathways. We found that i.n. vaccination of MERS-CoV RBD-Fc induced systemic humoral immune responses comparable to those induced by s.c. vaccination, including neutralizing antibodies, but more robust systemic cellular immune responses and significantly higher local mucosal immune responses in mouse lungs. This study suggests the potential of developing MERS-CoV RBD protein into an effective and safe mucosal candidate vaccine for prevention of respiratory tract infections caused by MERS-CoV.",,"['Ma, Cuiqing', 'Li, Ye', 'Wang, Lili', 'Zhao, Guangyu', 'Tao, Xinrong', 'Tseng, Chien-Te K', 'Zhou, Yusen', 'Du, Lanying', 'Jiang, Shibo']",,,,
,PMC,Better immunity in later life: a position paper,http://dx.doi.org/10.1007/s11357-014-9619-2,PMC4082593,,,"Ageing is the greatest challenge that health-care systems will have to deal with this century. This is because a wide spectrum of pathological impairments emerge in the later part of the human life course which sharply increase mortality and reduce quality of life. Dysfunction of the immune system with advancing age is of crucial importance to the development of disability in later life and finally death. Understanding immune ageing, immunosenescence, has long been recognised as an essential prerequisite for the delivery of effective interventions which will improve late life health. Ten years ago, the ImAginE consortium undertook a broad ranging series of projects which added significantly to our understanding of how fundamental ageing mechanisms drove immune decline. In the decade which followed, abundant evidence has accumulated from nonhuman model systems that ageing results from the progressive operation of a relatively few common processes which act across the major organ systems. These advances in fundamental understanding both allow better clarification of the potential cross-system dysregulation that occurs in ageing and open new avenues for intervention. Over the course of a 2-day workshop, the original ImAginE participants have considered these issues and present some suggestions for current priority areas in immunosenescence.",,"['Faragher, Richard', 'Frasca, Daniela', 'Remarque, Edmond', 'Pawelec, Graham', None]",,,,
,PMC,Deficiency of Melanoma Differentiation–associated Protein 5 Results in Exacerbated Chronic Postviral Lung Inflammation,http://dx.doi.org/10.1164/rccm.201307-1338OC,PMC3977719,,,"Rationale: Respiratory viral infections can result in the establishment of chronic lung diseases. Understanding the early innate immune mechanisms that participate in the development of chronic postviral lung disease may reveal new targets for therapeutic intervention. The intracellular viral sensor protein melanoma differentiation–associated protein 5 (MDA5) sustains the acute immune response to Sendai virus, a mouse pathogen that causes chronic lung inflammation, but its role in the development of postviral chronic lung disease is unknown. Objectives: To establish the role of MDA5 in the development of chronic lung disease. Methods: MDA5-deficient or control mice were infected with Sendai virus. The acute inflammatory response was evaluated by profiling chemokine and cytokine expression and by characterizing the composition of the cellular infiltrate. The impact of MDA5 on chronic lung pathology and function was evaluated through histological studies, degree of oxygen saturation, and responsiveness to carbachol. Measurements and Main Results: MDA5 deficiency resulted in normal virus replication and in a distinct profile of chemokines and cytokines that associated with acute lung neutropenia and enhanced accumulation of alternatively activated macrophages. Diminished expression of neutrophil-recruiting chemokines was also observed in cells infected with influenza virus, suggesting a key role of MDA5 in driving the early accumulation of neutrophils at the infection site. The biased acute inflammatory response of MDA5-deficient mice led to an enhanced chronic lung inflammation, epithelial cell hyperplasia, airway hyperreactivity, and diminished blood oxygen saturation. Conclusions: MDA5 modulates the development of chronic lung inflammation by regulating the early inflammatory response in the lung.",,"['Kim, Won-keun', 'Jain, Deepika', 'Sánchez, Melissa D.', 'Koziol-White, Cynthia J.', 'Matthews, Krystal', 'Ge, Moyar Q.', 'Haczku, Angela', 'Panettieri, Reynold A.', 'Frieman, Matthew B.', 'López, Carolina B.']",,,,
,PMC,Inhibition of canonical WNT signaling attenuates human leiomyoma cell growth,http://dx.doi.org/10.1016/j.fertnstert.2014.01.017,PMC4008647,,,"OBJECTIVE: Dysregulation of WNT signaling plays a central role in tumor cell growth and progression. Our goal was to assess the effect of three WNT/β-catenin pathway inhibitors, Inhibitor of β-Catenin And TCF4 (ICAT), niclosamide, and XAV939 on the proliferation of primary cultures of human uterine leiomyoma cells. DESIGN: Prospective study of human leiomyoma cells obtained from myomectomy or hysterectomy. SETTING: University research laboratory. PATIENT(S): Women (n=38) aged 27–53 years undergoing surgery. INTERVENTION(S): Adenoviral ICAT overexpression or treatment with varying concentrations of niclosamide or XAV939. MAIN OUTCOME MEASURE(S): Cell proliferation, cell death, WNT/β-catenin target gene expression or reporter gene regulation, β-catenin levels and cellular localization. RESULT(S): ICAT, niclosamide, or XAV939 inhibit WNT/β-catenin pathway activation and exert anti-proliferative effects in primary cultures of human leiomyoma cells. CONCLUSION(S): Three WNT/β-catenin pathway inhibitors specifically block human leiomyoma growth and proliferation, suggesting that the canonical WNT pathway may be a potential therapeutic target for the treatment of uterine leiomyoma. Our findings provide rationale for further preclinical and clinical evaluation of ICAT, niclosamide, and XAV939 as candidate anti-tumor agents for uterine leiomyoma.",,"['Ono, Masanori', 'Yin, Ping', 'Navarro, Antonia', 'Moravek, Molly B.', 'Coon, John S.', 'Druschitz, Stacy A.', 'Gottardi, Cara J.', 'Bulun, Serdar E.']",,,,
,PMC,Identification of an endocytic signal essential for the antiviral action of IFITM3,http://dx.doi.org/10.1111/cmi.12262,PMC4065222,,,"Members of the interferon-induced transmembrane (IFITM) protein family inhibit the entry of a wide range of viruses. Viruses often exploit the endocytosis pathways to invade host cells and escape from the endocytic vesicles often in response to low pH. Localization to these endocytic vesicles is essential for IFITM3 to interfere with the cytosolic entry of pH-dependent viruses. However, the nature of the sorting signal that targets IFITM3 to these vesicles is poorly defined. In this study, we report that IFITM3 possesses a YxxΦ sorting motif, i.e., 20-YEML-23, that enables IFITM3 to undergo endocytosis through binding to the μ2 subunit of the AP-2 complex. IFITM3 accumulates at the plasma membrane as a result of either mutating 20-YEML-23, depleting the μ2 subunit, or overexpressing μ2 mutants. Importantly, blocking endocytosis of IFITM3 abrogates its ability to inhibit pH-dependent viruses. We have therefore identified a critical sorting signal, namely 20-YEML-23, that controls both the endocytic trafficking and the antiviral action of IFITM3. This finding also reveals that as an endocytic protein, IFITM3 first arrives at the plasma membrane before it is endocytosed and further traffics to the late endosomes where it acts to impede virus entry.",,"['Jia, Rui', 'Xu, Fengwen', 'Qian, Jin', 'Yao, Yunfang', 'Miao, Chunhui', 'Zheng, Yi-Min', 'Liu, Shan-Lu', 'Guo, Fei', 'Geng, Yunqi', 'Qiao, Wentao', 'Liang, Chen']",,,,
,PMC,Advances and challenges in biosensor-based diagnosis of infectious diseases,http://dx.doi.org/10.1586/14737159.2014.888313,PMC4104499,,,"Rapid diagnosis of infectious diseases and timely initiation of appropriate treatment are critical determinants that promote optimal clinical outcomes and general public health. Conventional in vitro diagnostics for infectious diseases are time-consuming and require centralized laboratories, experienced personnel and bulky equipment. Recent advances in biosensor technologies have potential to deliver point-of-care diagnostics that match or surpass conventional standards in regards to time, accuracy and cost. Broadly classified as either label-free or labeled, modern biosensors exploit micro- and nanofabrication technologies and diverse sensing strategies including optical, electrical and mechanical transducers. Despite clinical need, translation of biosensors from research laboratories to clinical applications has remained limited to a few notable examples, such as the glucose sensor. Challenges to be overcome include sample preparation, matrix effects and system integration. We review the advances of biosensors for infectious disease diagnostics and discuss the critical challenges that need to be overcome in order to implement integrated diagnostic biosensors in real world settings.",,"['Sin, Mandy LY', 'Mach, Kathleen E', 'Wong, Pak Kin', 'Liao, Joseph C']",,,,
,PMC,Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain,http://dx.doi.org/10.1038/cmi.2013.61,PMC4003381,,,"Coronaviruses have developed various measures to evade innate immunity. We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. M protein from human coronavirus HKU1 does not inhibit IFN production. Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. TM1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. Mechanistically, TM1 is capable of binding with RIG-I, TRAF3, TBK1 and IKKε, and preventing the interaction of TRAF3 with its downstream effectors. Our work defines the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response.",,"['Siu, Kam-Leung', 'Chan, Chi-Ping', 'Kok, Kin-Hang', 'Chiu-Yat Woo, Patrick', 'Jin, Dong-Yan']",,,,
,PMC,"Nidovirus papain-like proteases: multifunctional enzymes with protease, deubiquitinating and deISGylating activities",http://dx.doi.org/10.1016/j.virusres.2014.01.025,PMC4125544,,,"Coronaviruses and arteriviruses, members of the order Nidovirales, are positive strand RNA viruses that encode large replicase polyproteins that are processed by viral proteases to generate the nonstructural proteins which mediate viral RNA synthesis. The viral papain-like proteases (PLPs) are critical for processing the amino-terminal end of the replicase and are attractive targets for antiviral therapies. With the analysis of the papain-like protease of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), came the realization of the multifunctional nature of these enzymes. Structural and enzymatic studies revealed that SARS-CoV PLpro can act as both a protease to cleave peptide bonds and also as a deubiquitinating (DUB) enzyme to cleave the isopeptide bonds found in polyubiquitin chains. Furthermore, viral DUBs can also remove the protective effect of conjugated ubiquitin-like molecules such as interferon stimulated gene 15 (ISG15). Extension of these studies to other coronaviruses and arteriviruses led to the realization that viral protease/DUB activity is conserved in many family members. Overexpression studies revealed that viral protease/DUB activity can modulate or block activation of the innate immune response pathway. Importantly, mutations that alter DUB activity but not viral protease activity have been identified and arteriviruses expressing DUB mutants stimulated higher levels of acute inflammatory cytokines after infection. Further understanding of the multifunctional nature of the Nidovirus PLP/DUBs may facilitate vaccine development. Here, we review studies describing the PLPs’ enzymatic activity and their role in virus pathogenesis.",,"['Mielech, Anna M.', 'Chen, Yafang', 'Mesecar, Andrew D.', 'Baker, Susan C.']",,,,
,PMC,Interferon-Stimulated Genes: A Complex Web of Host Defenses,http://dx.doi.org/10.1146/annurev-immunol-032713-120231,PMC4313732,,,"Interferon-stimulated gene (ISG) products take on a number of diverse roles. Collectively, they are highly effective at resisting and controlling pathogens. In this review, we begin by introducing interferon (IFN) and the JAK-STAT signaling pathway to highlight features that impact ISG production. Next, we describe ways in which ISGs both enhance innate pathogen-sensing capabilities and negatively regulate signaling through the JAK-STAT pathway. Several ISGs that directly inhibit virus infection are described with an emphasis on those that impact early and late stages of the virus life cycle. Finally, we describe ongoing efforts to identify and characterize antiviral ISGs, and we provide a forward-looking perspective on the ISG landscape.",,"['Schneider, William M.', 'Chevillotte, Meike Dittmann', 'Rice, Charles M.']",,,,
,PMC,Kingdom-agnostic Metagenomics and the Importance of Complete Characterization of Enteric Microbial Communities,http://dx.doi.org/10.1053/j.gastro.2014.02.001,PMC4009354,,,"Advanced sequencing techniques have shown that bacteria are not the only complex and important microbes in the human intestine. Non-bacterial organisms, particularly the virome and the mycobiome, are important regulators of intestinal immunity and inflammation. The virome is mucosal and systemic; it can alter the host response to bacteria and interact with host genes and bacteria to contribute to disease pathogenesis. The human mycobiome is also complex and can contribute to intestinal inflammation. We review what has recently been learned about the non-bacterial and non-archaeal microbes in the gastrointestinal tract, discussing their potential effects on health and disease and analytical approaches for their study. Studies of associations between the microbiome and intestinal pathology should incorporate kingdom-agnostic approaches if we are to fully understand intestinal health and disease.",,"['Norman, Jason M.', 'Handley, Scott A.', 'Virgin, Herbert W.']",,,,
,PMC,Inositol-requiring Enzyme 1 Inhibits Respiratory Syncytial Virus Replication,http://dx.doi.org/10.1074/jbc.M113.510594,PMC3953267,,,"Despite being a major health problem, respiratory syncytial virus (RSV) infections remain without specific therapy. Identification of novel host cellular responses that play a role in the pathogenesis of RSV infection is needed for therapeutic development. The endoplasmic reticulum (ER) stress response is an evolutionarily conserved cellular signaling cascade that has been implicated in multiple biological phenomena, including the pathogenesis of some viral infections. In this study, we investigate the role of the ER stress response in RSV infection using an in vitro A549 cell culture model. We found that RSV infection induces a non-canonical ER stress response with preferential activation of the inositol-requiring enzyme 1 (IRE1) and activated transcription factor 6 (ATF6) pathways with no concomitant significant activation of the protein kinase R-like ER kinase (PERK) pathway. Furthermore, we discovered that IRE1 has an inhibitory effect on RSV replication. Our data characterize, for the first time, the nature of the ER stress response in the setting of RSV infection and identify the IRE1 stress pathway as a novel cellular anti-RSV defense mechanism.",,"['Hassan, Ihab', 'Gaines, Kayla S.', 'Hottel, Wesley J.', 'Wishy, Ryan M.', 'Miller, Sara E.', 'Powers, Linda S.', 'Rutkowski, D. Thomas', 'Monick, Martha M.']",,,,
,PMC,Investigating the Congruence of Crowdsourced Information With Official Government Data: The Case of Pediatric Clinics,http://dx.doi.org/10.2196/jmir.3078,PMC3936264,24496094,CC BY,"BACKGROUND: Health 2.0 is a benefit to society by helping patients acquire knowledge about health care by harnessing collective intelligence. However, any misleading information can directly affect patients’ choices of hospitals and drugs, and potentially exacerbate their health condition. OBJECTIVE: This study investigates the congruence between crowdsourced information and official government data in the health care domain and identifies the determinants of low congruence where it exists. In-line with infodemiology, we suggest measures to help the patients in the regions vulnerable to inaccurate health information. METHODS: We text-mined multiple online health communities in South Korea to construct the data for crowdsourced information on public health services (173,748 messages). Kendall tau and Spearman rank order correlation coefficients were used to compute the differences in 2 ranking systems of health care quality: actual government evaluations of 779 hospitals and mining results of geospecific online health communities. Then we estimated the effect of sociodemographic characteristics on the level of congruence by using an ordinary least squares regression. RESULTS: The regression results indicated that the standard deviation of married women’s education (P=.046), population density (P=.01), number of doctors per pediatric clinic (P=.048), and birthrate (P=.002) have a significant effect on the congruence of crowdsourced data (adjusted R (2)=.33). Specifically, (1) the higher the birthrate in a given region, (2) the larger the variance in educational attainment, (3) the higher the population density, and (4) the greater the number of doctors per clinic, the more likely that crowdsourced information from online communities is congruent with official government data. CONCLUSIONS: To investigate the cause of the spread of misleading health information in the online world, we adopted a unique approach by associating mining results on hospitals from geospecific online health communities with the sociodemographic characteristics of corresponding regions. We found that the congruence of crowdsourced information on health care services varied across regions and that these variations could be explained by geospecific demographic factors. This finding can be helpful to governments in reducing the potential risk of misleading online information and the accompanying safety issues.",2014 Feb 3,"['Kim, Minki', 'Jung, Yuchul', 'Jung, Dain', 'Hur, Cinyoung']",J Med Internet Res,,,
,PMC,Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes,http://dx.doi.org/10.1073/pnas.1312296111,PMC3932933,,,"The human proteome contains a plethora of short linear motifs (SLiMs) that serve as binding interfaces for modular protein domains. Such interactions are crucial for signaling and other cellular processes, but are difficult to detect because of their low to moderate affinities. Here we developed a dedicated approach, proteomic peptide-phage display (ProP-PD), to identify domain–SLiM interactions. Specifically, we generated phage libraries containing all human and viral C-terminal peptides using custom oligonucleotide microarrays. With these libraries we screened the nine PSD-95/Dlg/ZO-1 (PDZ) domains of human Densin-180, Erbin, Scribble, and Disks large homolog 1 for peptide ligands. We identified several known and putative interactions potentially relevant to cellular signaling pathways and confirmed interactions between full-length Scribble and the target proteins β-PIX, plakophilin-4, and guanylate cyclase soluble subunit α-2 using colocalization and coimmunoprecipitation experiments. The affinities of recombinant Scribble PDZ domains and the synthetic peptides representing the C termini of these proteins were in the 1- to 40-μM range. Furthermore, we identified several well-established host–virus protein–protein interactions, and confirmed that PDZ domains of Scribble interact with the C terminus of Tax-1 of human T-cell leukemia virus with micromolar affinity. Previously unknown putative viral protein ligands for the PDZ domains of Scribble and Erbin were also identified. Thus, we demonstrate that our ProP-PD libraries are useful tools for probing PDZ domain interactions. The method can be extended to interrogate all potential eukaryotic, bacterial, and viral SLiMs and we suggest it will be a highly valuable approach for studying cellular and pathogen–host protein–protein interactions.",,"['Ivarsson, Ylva', 'Arnold, Roland', 'McLaughlin, Megan', 'Nim, Satra', 'Joshi, Rakesh', 'Ray, Debashish', 'Liu, Bernard', 'Teyra, Joan', 'Pawson, Tony', 'Moffat, Jason', 'Li, Shawn Shun-Cheng', 'Sidhu, Sachdev S.', 'Kim, Philip M.']",,,,
,PMC,UVRAG is required for virus entry through combinatorial interaction with the class C-Vps complex and SNAREs,http://dx.doi.org/10.1073/pnas.1320629111,PMC3932887,,,"Enveloped viruses exploit the endomembrane system to enter host cells. Through a cascade of membrane-trafficking events, virus-bearing vesicles fuse with acidic endosomes and/or lysosomes mediated by SNAREs triggering viral fusion. However, the molecular mechanisms underlying this process remain elusive. Here, we found that UV-radiation resistance-associated gene (UVRAG), an autophagic tumor suppressor, is required for the entry of the prototypic negative-strand RNA virus, including influenza A virus and vesicular stomatitis virus, by a mechanism independent of IFN and autophagy. UVRAG mediates viral endocytic transport and membrane penetration through interactions with the class C vacuolar protein sorting (C-Vps) tethering complex and endosomal glutamine-containing SNAREs [syntaxin 7 (STX7), STX8, and vesicle transport through t-SNARE homolog 1B (Vti1b)], leading to the assembly of a fusogenic trans-SNARE complex involving vesicle-associated membrane protein (VAMP8), but not VAMP7. Indeed, UVRAG stimulates VAMP8 translocation to virus-bearing endosomes. Inhibition of VAMP8, but not VAMP7, significantly reduces viral entry. Our data indicate that UVRAG, in concert with C-Vps, regulates viral entry by assembling a specific fusogenic SNARE complex. Thus, UVRAG governs downstream viral entry, highlighting an important pathway capable of potential antiviral therapeutics.",,"['Pirooz, Sara Dolatshahi', 'He, Shanshan', 'Zhang, Tian', 'Zhang, Xiaowei', 'Zhao, Zhen', 'Oh, Soohwan', 'O’Connell, Douglas', 'Khalilzadeh, Payam', 'Amini-Bavil-Olyaee, Samad', 'Farzan, Michael', 'Liang, Chengyu']",,,,
,PMC,THE TIME IS NOW: MOVING TOWARDS VIRUS-SPECIFIC T CELLS AFTER ALLOGENIC HEMATOPOIETIC STEM CELL TRANSPLANTATION AS THE STANDARD OF CARE,http://dx.doi.org/10.1016/j.jcyt.2013.11.010,PMC3928596,,,"Adoptive immunotherapy—in particulary T cell therapy—has recently emerged as a useful strategy with the potential to overcome many of the limitations of antiviral drugs for the treatment of viral complications after hematopietic stem cell transplantation (HSCT). In this review we briefly summarize the current methods for virus- specific T cell isolation or selection and we report results from clinical trials employing these techniques, focusing specifically on the strategies aimed to broaden the application of this technology.",,"['Saglio, Francesco', 'Hanley, Patrick J', 'Bollard, Catherine M']",,,,
,PMC,Vaccinated C57BL/6 Mice Develop Protective and Memory T Cell Responses to Coccidioides posadasii Infection in the Absence of Interleukin-10,http://dx.doi.org/10.1128/IAI.01148-13,PMC3911407,,,"High concentrations of lung tissue-associated interleukin-10 (IL-10), an anti-inflammatory and immunosuppressive cytokine, correlate with susceptibility of mice to Coccidioides spp. infection. In this study, we found that macrophages, dendritic cells, neutrophils, and both CD8(+) and CD4(+) T cells recruited to Coccidioides posadasii-infected lungs of nonvaccinated and vaccinated mice contributed to the production of IL-10. The major IL-10-producing leukocytes were CD8(+) T cells, neutrophils, and macrophages in lungs of nonvaccinated mice, while both Foxp3(+) and Foxp3(−) subsets of IL-10(+) CD4(+) T cells were significantly elevated in vaccinated mice. Profiles of the recruited leukocytes in lungs revealed that only CD4(+) T cells were significantly increased in IL-10(−/−) knockout mice compared to their wild-type counterparts. Furthermore, ex vivo recall assays showed that CD4(+) T cells isolated from vaccinated IL-10(−/−) mice compared to vaccinated wild-type mice produced significantly higher amounts of IL-2, gamma interferon (IFN-γ), IL-4, IL-6, and IL-17A in the presence of a coccidioidal antigen, indicating that IL-10 suppresses Th1, Th2, and Th17 immunity to Coccidioides infection. Analysis of absolute numbers of CD44(+) CD62L(−) CD4(+) T effector memory T cells (T(EM)) and IFN-γ- and IL-17A-producing CD4(+) T cells in the lungs of Coccidioides-infected mice correlated with better fungal clearance in nonvaccinated IL-10(−/−) mice than in nonvaccinated wild-type mice. Our results suggest that IL-10 suppresses CD4(+) T-cell immunity in nonvaccinated mice during Coccidioides infection but does not impede the development of a memory response nor exacerbate immunopathology of vaccinated mice over at least a 4-month period after the last immunization.",,"['Hung, Chiung-Yu', 'Castro-Lopez, Natalia', 'Cole, Garry T.']",,,,
,PMC,Detection of New Bunyavirus RNA by Reverse Transcription–Loop-Mediated Isothermal Amplification,http://dx.doi.org/10.1128/JCM.01813-13,PMC3911317,,,"Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging and epidemic infectious disease in central and northeast China. It is caused by New Bunyavirus and carries an average 12% case fatality rate. Early and rapid detection is critical for prevention and control of New Bunyavirus infection, since no vaccine or antiviral drugs are currently available, and prevention requires careful attention to control of the suspected tick vector. In this study, a simple and sensitive reverse transcription–loop-mediated isothermal amplification (RT-LAMP) assay was developed for rapid detection of New Bunyavirus. The detection limit of the RT-LAMP assay was approximately 10(3) 50% tissue culture infective doses/ml of New Bunyavirus in culture supernatants, and no cross-reactive amplification of other viruses known to cause similar clinical manifestations was observed. The assay was further evaluated using 138 specimens from clinically suspected SFTS and 40 laboratory-proven hantavirus infection with fever and renal syndrome patients, and the assay exhibited 97% agreement compared to real-time RT-PCR and conventional RT-PCR. Using real-time RT-PCR as the diagnostic gold standard, RT-LAMP was 99% sensitive and 100% specific. The RT-LAMP assay could become a useful alternative in clinical diagnosis of SFTS caused by New Bunyavirus, especially in resource-limited hospitals or rural clinics of China.",,"['Huang, Xue-Yong', 'Hu, Xiao-Ning', 'Ma, Hong', 'Du, Yan-Hua', 'Ma, Hong-Xia', 'Kang, Kai', 'You, Ai-Guo', 'Wang, Hai-Feng', 'Zhang, Li', 'Chen, Hao-Min', 'Dumler, J. Stephen', 'Xu, Bian-Li']",,,,
,PMC,Wild-type and innate immune-deficient mice are not susceptible to the Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1099/vir.0.060640-0,PMC3917065,,,"The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging highly pathogenic virus causing almost 50 % lethality in infected individuals. The development of a small-animal model is critical for the understanding of this virus and to aid in development of countermeasures against MERS-CoV. We found that BALB/c, 129/SvEv and 129/SvEv STAT1 knockout mice are not permissive to MERS-CoV infection. The lack of infection may be due to the low level of mRNA and protein for the MERS-CoV receptor, dipeptidyl peptidase 4 (DPP4), in the lungs of mice. The low level of DPP4 in the lungs likely contributes to the lack of viral replication in these mouse models and suggests that a transgenic mouse model expressing DPP4 to higher levels is necessary to create a mouse model for MERS-CoV.",,"['Coleman, Christopher M.', 'Matthews, Krystal L.', 'Goicochea, Lindsay', 'Frieman, Matthew B.']",,,,
,PMC,Novel Treatment with Neuroprotective and Antiviral Properties against a Neuroinvasive Human Respiratory Virus,http://dx.doi.org/10.1128/JVI.02972-13,PMC3911624,,,"Human coronaviruses (HCoVs) are recognized respiratory pathogens with neuroinvasive and neurotropic properties in mice and humans. HCoV strain OC43 (HCoV-OC43) can infect and persist in human neural cells and activate neuroinflammatory and neurodegenerative mechanisms, suggesting that it could be involved in neurological disease of unknown etiology in humans. Moreover, we have shown that HCoV-OC43 is neurovirulent in susceptible mice, causing encephalitis, and that a viral mutant with a single point mutation in the viral surface spike (S) protein induces a paralytic disease that involves glutamate excitotoxicity in susceptible mice. Herein, we show that glutamate recycling via the glial transporter 1 protein transporter and glutamine synthetase are central to the dysregulation of glutamate homeostasis and development of motor dysfunctions and paralytic disease in HCoV-OC43-infected mice. Moreover, memantine, an N-methyl-d-aspartate receptor antagonist widely used in the treatment of neurological diseases in humans, improved clinical scores related to paralytic disease and motor disabilities by partially restoring the physiological neurofilament phosphorylation state in virus-infected mice. Interestingly, memantine attenuated mortality rates and body weight loss and reduced HCoV-OC43 replication in the central nervous system in a dose-dependent manner. This novel action of memantine on viral replication strongly suggests that it could be used as an antiviral agent to directly limit viral replication while improving neurological symptoms in various neurological diseases with a viral involvement. IMPORTANCE",,"['Brison, Elodie', 'Jacomy, Hélène', 'Desforges, Marc', 'Talbot, Pierre J.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.03583-13,PMC3911603,,,,,,,,,
,PMC,Adenosine Deaminase Acts as a Natural Antagonist for Dipeptidyl Peptidase 4-Mediated Entry of the Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.02935-13,PMC3911594,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) replicates in cells of different species using dipeptidyl peptidase 4 (DPP4) as a functional receptor. Here we show the resistance of ferrets to MERS-CoV infection and inability of ferret DDP4 to bind MERS-CoV. Site-directed mutagenesis of amino acids variable in ferret DPP4 thus revealed the functional human DPP4 virus binding site. Adenosine deaminase (ADA), a DPP4 binding protein, competed for virus binding, acting as a natural antagonist for MERS-CoV infection.",,"['Raj, V. Stalin', 'Smits, Saskia L.', 'Provacia, Lisette B.', 'van den Brand, Judith M. A.', 'Wiersma, Lidewij', 'Ouwendijk, Werner J. D.', 'Bestebroer, Theo M.', 'Spronken, Monique I.', 'van Amerongen, Geert', 'Rottier, Peter J. M.', 'Fouchier, Ron A. M.', 'Bosch, Berend Jan', 'Osterhaus, Albert D.M.E.', 'Haagmans, Bart L.']",,,,
,PMC,A Novel Activation Mechanism of Avian Influenza Virus H9N2 by Furin,http://dx.doi.org/10.1128/JVI.02648-13,PMC3911587,,,"Avian influenza virus H9N2 is prevalent in waterfowl and has become endemic in poultry in Asia and the Middle East. H9N2 influenza viruses have served as a reservoir of internal genes for other avian influenza viruses that infect humans, and several cases of human infection by H9N2 influenza viruses have indicated its pandemic potential. Fortunately, an extensive surveillance program enables close monitoring of H9N2 influenza viruses worldwide and has generated a large repository of virus sequences and phylogenetic information. Despite the large quantity of sequences in different databases, very little is known about specific virus isolates and their pathogenesis. Here, we characterize a low-pathogenicity avian influenza virus, A/chicken/Israel/810/2001 (H9N2) (Israel810), which is representative of influenza virus strains that have caused severe morbidity and mortality in poultry farms. We show that under certain circumstances the Israel810 hemagglutinin (HA) can be activated by furin, a hallmark of highly pathogenic avian influenza virus. We demonstrate that Israel810 HA can be cleaved in cells with high levels of furin expression and that a mutation that eliminates a glycosylation site in HA(1) allows the Israel810 HA to gain universal cleavage in cell culture. Pseudoparticles generated from Israel810 HA, or the glycosylation mutant, transduce cells efficiently. In contrast, introduction of a polybasic cleavage site into Israel810 HA leads to pseudoviruses that are compromised for transduction. Our data indicate a mechanism for an H9N2 evolutionary pathway that may allow it to gain virulence in a distinct manner from H5 and H7 influenza viruses.",,"['Tse, Longping V.', 'Hamilton, Alice M.', 'Friling, Tamar', 'Whittaker, Gary R.']",,,,
,PMC,New Small Molecule Entry Inhibitors Targeting Hemagglutinin-Mediated Influenza A Virus Fusion,http://dx.doi.org/10.1128/JVI.01225-13,PMC3911584,,,"Influenza viruses are a major public health threat worldwide, and options for antiviral therapy are limited by the emergence of drug-resistant virus strains. The influenza virus glycoprotein hemagglutinin (HA) plays critical roles in the early stage of virus infection, including receptor binding and membrane fusion, making it a potential target for the development of anti-influenza drugs. Using pseudotype virus-based high-throughput screens, we have identified several new small molecules capable of inhibiting influenza virus entry. We prioritized two novel inhibitors, MBX2329 and MBX2546, with aminoalkyl phenol ether and sulfonamide scaffolds, respectively, that specifically inhibit HA-mediated viral entry. The two compounds (i) are potent (50% inhibitory concentration [IC(50)] of 0.3 to 5.9 μM); (ii) are selective (50% cytotoxicity concentration [CC(50)] of >100 μM), with selectivity index (SI) values of >20 to 200 for different influenza virus strains; (iii) inhibit a wide spectrum of influenza A viruses, which includes the 2009 pandemic influenza virus A/H1N1/2009, highly pathogenic avian influenza (HPAI) virus A/H5N1, and oseltamivir-resistant A/H1N1 strains; (iv) exhibit large volumes of synergy with oseltamivir (36 and 331 μM(2) % at 95% confidence); and (v) have chemically tractable structures. Mechanism-of-action studies suggest that both MBX2329 and MBX2546 bind to HA in a nonoverlapping manner. Additional results from HA-mediated hemolysis of chicken red blood cells (cRBCs), competition assays with monoclonal antibody (MAb) C179, and mutational analysis suggest that the compounds bind in the stem region of the HA trimer and inhibit HA-mediated fusion. Therefore, MBX2329 and MBX2546 represent new starting points for chemical optimization and have the potential to provide valuable future therapeutic options and research tools to study the HA-mediated entry process.",,"['Basu, Arnab', 'Antanasijevic, Aleksandar', 'Wang, Minxiu', 'Li, Bing', 'Mills, Debra M.', 'Ames, Jessica A.', 'Nash, Peter J.', 'Williams, John D.', 'Peet, Norton P.', 'Moir, Donald T.', 'Prichard, Mark N.', 'Keith, Kathy A.', 'Barnard, Dale L.', 'Caffrey, Michael', 'Rong, Lijun', 'Bowlin, Terry L.']",,,,
,PMC,Bovine Ephemeral Fever Rhabdovirus α1 Protein Has Viroporin-Like Properties and Binds Importin β1 and Importin 7,http://dx.doi.org/10.1128/JVI.01812-13,PMC3911578,,,"Bovine ephemeral fever virus (BEFV) is an arthropod-borne rhabdovirus that is classified as the type species of the genus Ephemerovirus. In addition to the five canonical rhabdovirus structural proteins (N, P, M, G, and L), the large and complex BEFV genome contains several open reading frames (ORFs) between the G and L genes (α1, α2/α3, β, and γ) encoding proteins of unknown function. We show that the 10.5-kDa BEFV α1 protein is expressed in infected cells and, consistent with previous predictions based on its structure, has the properties of a viroporin. Expression of a BEFV α1-maltose binding protein (MBP) fusion protein in Escherichia coli was observed to inhibit cell growth and increase membrane permeability to hygromycin B. Increased membrane permeability was also observed in BEFV-infected mammalian cells (but not cells infected with an α1-deficient BEFV strain) and in cells expressing a BEFV α1-green fluorescent protein (GFP) fusion protein, which was shown by confocal microscopy to localize to the Golgi complex. Furthermore, the predicted C-terminal cytoplasmic domain of α1, which contains a strong nuclear localization signal (NLS), was translocated to the nucleus when expressed independently, and in an affinity chromatography assay employing a GFP trap, the full-length α1 was observed to interact specifically with importin β1 and importin 7 but not with importin α3. These data suggest that, in addition to its function as a viroporin, BEFV α1 may modulate components of nuclear trafficking pathways, but the specific role thereof remains unclear. IMPORTANCE",,"['Joubert, D. Albert', 'Blasdell, Kim R.', 'Audsley, Michelle D.', 'Trinidad, Lee', 'Monaghan, Paul', 'Dave, Keyur A.', 'Lieu, Kim G.', 'Amos-Ritchie, Rachel', 'Jans, David A.', 'Moseley, Gregory W.', 'Gorman, Jeffrey J.', 'Walker, Peter J.']",,,,
,PMC,Differential Responses of Disease-Resistant and Disease-Susceptible Primate Macrophages and Myeloid Dendritic Cells to Simian Hemorrhagic Fever Virus Infection,http://dx.doi.org/10.1128/JVI.02633-13,PMC3911543,,,"Simian hemorrhagic fever virus (SHFV) causes a fatal hemorrhagic fever in macaques but an asymptomatic, persistent infection in baboons. To investigate factors contributing to this differential infection outcome, the targets of SHFV infection, macrophages (MΦs) and myeloid dendritic cells (mDCs), were differentiated from macaque and baboon peripheral blood monocytes and used to compare viral replication and cell responses. SHFV replicated in >90% of macaque MΦs but in only ∼10% of baboon MΦs. Although SHFV infected ∼50% of macaque and baboon mDCs, virus replication was efficient in macaque but not in baboon mDCs. Both types of macaque cultures produced higher virus yields than baboon cultures. A more efficient type I interferon response and the production of proinflammatory cytokines, including interleukin-1β (IL-1β), IL-6, IL-12/23(p40), tumor necrosis factor alpha (TNF-α), and macrophage inflammatory protein 1α (MIP-1α), in response to SHFV infection were observed in macaque but not baboon cultures, suggesting less efficient counteraction of these responses by viral proteins in macaque cells. Baboon cultures produced higher levels of IL-10 than macaque cultures both prior to and after SHFV infection. In baboon but not macaque cell cultures, SHFV infection upregulated IL-10R1, a subunit of the IL-10 receptor (IL-10R), and also SOCS3, a negative regulator of proinflammatory cytokine production. Incubation of macaque cultures with human IL-10 before and/or after SHFV infection decreased production of IL-6, IL-1β, and MIP-1α but not TNF-α, suggesting a role for IL-10 in suppressing SHFV-induced proinflammatory cytokine production in macaques.",,"['Vatter, Heather A.', 'Brinton, Margo A.']",,,,
,PMC,"Differential Inhibitory Effects of Cyanovirin-N, Griffithsin, and Scytovirin on Entry Mediated by Envelopes of Gammaretroviruses and Deltaretroviruses",http://dx.doi.org/10.1128/JVI.02553-13,PMC3911537,,,"The antiviral lectins griffithsin (GRFT), cyanovirin-N (CV-N), and scytovirin (SVN), which inhibit several enveloped viruses, including lentiviruses, were examined for their ability to inhibit entry mediated by Env proteins of delta- and gammaretroviruses. The glycoproteins from human T-cell leukemia virus type 1 (HTLV-1) were resistant to the antiviral effects of all three lectins. For gammaretroviruses, CV-N inhibited entry mediated by some but not all of the envelopes examined, whereas GRFT and SVN displayed only little or no effect.",,"['Jensen, Stig M. R.', 'Ruscetti, Francis W.', 'Rein, Alan', 'Bertolette, Daniel C.', 'Saucedo, Carrie J.', ""O'Keefe, Barry R."", 'Jones, Kathryn S.']",,,,
,PMC,Evidence of Pervasive Biologically Functional Secondary Structures within the Genomes of Eukaryotic Single-Stranded DNA Viruses,http://dx.doi.org/10.1128/JVI.03031-13,PMC3911531,,,"Single-stranded DNA (ssDNA) viruses have genomes that are potentially capable of forming complex secondary structures through Watson-Crick base pairing between their constituent nucleotides. A few of the structural elements formed by such base pairings are, in fact, known to have important functions during the replication of many ssDNA viruses. Unknown, however, are (i) whether numerous additional ssDNA virus genomic structural elements predicted to exist by computational DNA folding methods actually exist and (ii) whether those structures that do exist have any biological relevance. We therefore computationally inferred lists of the most evolutionarily conserved structures within a diverse selection of animal- and plant-infecting ssDNA viruses drawn from the families Circoviridae, Anelloviridae, Parvoviridae, Nanoviridae, and Geminiviridae and analyzed these for evidence of natural selection favoring the maintenance of these structures. While we find evidence that is consistent with purifying selection being stronger at nucleotide sites that are predicted to be base paired than at sites predicted to be unpaired, we also find strong associations between sites that are predicted to pair with one another and site pairs that are apparently coevolving in a complementary fashion. Collectively, these results indicate that natural selection actively preserves much of the pervasive secondary structure that is evident within eukaryote-infecting ssDNA virus genomes and, therefore, that much of this structure is biologically functional. Lastly, we provide examples of various highly conserved but completely uncharacterized structural elements that likely have important functions within some of the ssDNA virus genomes analyzed here.",,"['Muhire, Brejnev Muhizi', 'Golden, Michael', 'Murrell, Ben', 'Lefeuvre, Pierre', 'Lett, Jean-Michel', 'Gray, Alistair', 'Poon, Art Y. F.', 'Ngandu, Nobubelo Kwanele', 'Semegni, Yves', 'Tanov, Emil Pavlov', 'Monjane, Adérito Luis', 'Harkins, Gordon William', 'Varsani, Arvind', 'Shepherd, Dionne Natalie', 'Martin, Darren Patrick']",,,,
,PMC,Exon-Skipping Antisense Oligonucleotides to Correct Missplicing in Neurogenetic Diseases,http://dx.doi.org/10.1089/nat.2013.0461,PMC3922311,,,"Alternative splicing is an important regulator of the transcriptome. However, mutations may cause alteration of splicing patterns, which in turn leads to disease. During the past 10 years, exon skipping has been looked upon as a powerful tool for correction of missplicing in disease and progress has been made towards clinical trials. In this review, we discuss the use of antisense oligonucleotides to correct splicing defects through exon skipping, with a special focus on diseases affecting the nervous system, and the latest stage achieved in its progress.",,"['Siva, Kavitha', 'Covello, Giuseppina', 'Denti, Michela A.']",,,,
,PMC,Nanoparticle Delivery of Antisense Oligonucleotides and Their Application in the Exon Skipping Strategy for Duchenne Muscular Dystrophy,http://dx.doi.org/10.1089/nat.2013.0450,PMC3922138,,,"Antisense therapy is a powerful tool for inducing post-transcriptional modifications and thereby regulating target genes associated with disease. There are several classes of antisense oligonucleotides (AONs) with therapeutic use, such as double-stranded RNAs (interfering RNAs, utilized for gene silencing, and single-stranded AONs with various chemistries, which are useful for antisense targeting of micro-RNAs and mRNAs. In particular, the use of AONs for exon skipping, by targeting pre-mRNA, is proving to be a highly promising therapy for some genetic disorders like Duchenne muscular dystrophy and spinal muscular atrophy. However, AONs are unable to cross the plasma membrane unaided, and several other obstacles still remain to be overcome, in particular their instability due to their nuclease sensitivity and their lack of tissue specificity. Various drug delivery systems have been explored to improve the bioavailability of nucleic acids, and nanoparticles (NPs) have been suggested as potential vectors for DNA/RNA. This review describes the recent progress in AON conjugation with natural and synthetic delivery systems, and provides an overview of the efficacy of NP-AON complexes as an exon-skipping treatment for Duchenne muscular dystrophy.",,"['Falzarano, Maria Sofia', 'Passarelli, Chiara', 'Ferlini, Alessandra']",,,,
,PMC,Incidence and Etiology of Acute Lower Respiratory Tract Infections in Hospitalized Children Younger Than 5 Years in Rural Thailand,http://dx.doi.org/10.1097/INF.0000000000000062,PMC4667718,,,"BACKGROUND: Pneumonia remains a leading cause of under-five morbidity and mortality globally. Comprehensive incidence, epidemiologic and etiologic data are needed to update prevention and control strategies. METHODS: We conducted active, population-based surveillance for hospitalized cases of acute lower respiratory tract infections (ALRI) among children <5 years of age in rural thailand. ALRI cases were systematically sampled for an etiology study that tested nasopharyngeal specimens by polymerase chain reaction; children without ALRI were enrolled as controls from outpatient clinics. RESULTS: We identified 28,543 hospitalized ALRI cases from 2005 to 2010. Among the 49% with chest radiographs, 63% had findings consistent with pneumonia as identified by 2 study radiologists. The hospitalized ALRI incidence rate was 5772 per 100,000 child-years (95% confidence interval: 5707, 5837) and was higher in boys versus girls (incidence rate ratio 1.38, 95% confidence interval: 1.35–1.41) and in children 6–23 months of age versus other age groups (incidence rate ratio 1.76, 95% confidence interval: 1.69–1.84). Viruses most commonly detected in ALRI cases were respiratory syncytial virus (19.5%), rhinoviruses (18.7%), bocavirus (12.8%) and influenza viruses (8%). Compared with controls, ALRI cases were more likely to test positive for respiratory syncytial virus, influenza, adenovirus, human metapneumovirus and parainfluenza viruses 1 and 3 (P ≤ 0.01 for all). Bloodstream infections, most commonly Streptococcus pneumoniae and nontyphoidal Salmonella, accounted for 1.8% of cases. CONCLUSIONS: Our findings underscore the high burden of hospitalization for ALRI and the importance of viral pathogens among children in Thailand. Interventions targeting viral pathogens coupled with improved diagnostic approaches, especially for bacteria, are critical for better understanding of ALRI etiology, prevention and control.",,"['Hasan, Reem', 'Rhodes, Julia', 'Thamthitiwat, Somsak', 'Olsen, Sonja J.', 'Prapasiri, Prabda', 'Naorat, Sathapana', 'Chittaganpitch, Malinee', 'Henchaichon, Sununta', 'Dejsirilert, Surang', 'Srisaengchai, Prasong', 'Sawatwong, Pongpun', 'Jorakate, Possawat', 'Kaewpan, Anek', 'Fry, Alicia M.', 'Erdman, Dean', 'Chuananon, Somchai', 'Amornintapichet, Tussanee', 'Maloney, Susan A.', 'Baggett, Henry C.']",,,,
,PMC,The fecal virome of domesticated animals,http://dx.doi.org/10.1007/s13337-014-0192-1,PMC4188178,,,"Next-generation sequencing is a new research tool in our hands helping us to explore still unknown fields of human and veterinary virology. Metagenomic analysis has enabled the discovery of putative novel pathogens and the identification of the etiologic agents of several diseases, solving long-standing mysteries caused by divergent viruses. This approach has been used in several studies investigating fecal samples of livestock, and companion animal species, providing information on the diversity of animal fecal virome, helping the elucidation of the etiology of diarrheal disease in animals and identifying potential zoonotic and emerging viruses.",,"['Mihalov-Kovács, Eszter', 'Fehér, Enikő', 'Martella, Vito', 'Bányai, Krisztián', 'Farkas, Szilvia L.']",,,,
,PMC,Favipiravir (T-705) protects against peracute Rift Valley fever virus infection and reduces delayed-onset neurologic disease observed with ribavirin treatment,http://dx.doi.org/10.1016/j.antiviral.2014.01.016,PMC3975078,,,"Rift Valley Fever is a zoonotic, arthropod-borne disease that affects livestock and humans. The etiologic agent, Rift Valley fever virus (RVFV; Bunyaviridae, Phlebovirus) is primarily transmitted through mosquito bites, but can also be transmitted by exposure to infectious aerosols. There are presently no licensed vaccines or therapeutics to prevent or treat severe RVFV infection in humans. We have previously reported on the activity of favipiravir (T-705) against the MP-12 vaccine strain of RVFV and other bunyaviruses in cell culture. In addition, efficacy has also been documented in mouse and hamster models of infection with the related Punta Toro virus. Here, we challenged hamsters with the highly pathogenic ZH501 strain of RVFV to evaluate the activity of favipiravir against lethal infection. Subcutaneous RVFV challenge resulted in substantial serum and tissue viral loads and caused severe disease and mortality within 2–3 days after infection. Oral favipiravir (200 mg/kg/day) prevented mortality in 60% or greater in hamsters challenged with RVFV when administered within 1 or 6 h post-exposure and reduced RVFV titers in serum and tissues relative to the time of treatment initiation. In contrast, although ribavirin (75 mg/kg/day) was effective at protecting animals from the peracute RVFV disease, most ultimately succumbed from a delayed-onset neurologic disease associated with high RVFV burden in the brain observed in moribund animals. When combined, T-705 and ribavirin treatment started 24 h post-infection significantly improved survival outcome and reduced serum and tissue virus titers compared to monotherapy. Our findings demonstrate significant post-RVFV exposure efficacy with favipiravir against both peracute disease and delayed-onset neuroinvasion, and suggest added benefit when combined with ribavirin.",,"['Scharton, Dionna', 'Bailey, Kevin W.', 'Vest, Zachary', 'Westover, Jonna B.', 'Kumaki, Yohichi', 'Van Wettere, Arnaud', 'Furuta, Yousuke', 'Gowen, Brian B.']",,,,
,PMC,Protection of Ferrets from Pulmonary Injury Due to H1N1 2009 Influenza Virus Infection: Immunopathology Tractable by Sphingosine-1-Phosphate 1 Receptor Agonist Therapy,http://dx.doi.org/10.1016/j.virol.2014.01.003,PMC3954990,,,"Influenza infection of humans remains an important public health problem. Vaccine strategies result in a significant but only partial control (65-85%) of infection. Thus, chemotherapeutic approaches are needed to provide a solution both for vaccine failures and to limit infection in the unvaccinated population. Previously (Walsh et al. 2011, Teijaro et al. 2011) documented that sphingosine-1-phosphate 1 receptor (S1P1R) agonists significantly protected mice against pathogenic H1N1 influenza virus by limiting immunopathologic damage while allowing host control of the infection. Here we extend that observation by documenting S1P1R agonist can control pathogenic H1N1 influenza infection in ferrets. S1P1R agonist was more effective in reducing pulmonary injury than the antiviral drug oseltamivir but, importantly, combined therapy was significantly more effective than either therapy alone.",,"['Teijaro, John R.', 'Walsh, Kevin B.', 'Long, James P.', 'Tordoff, Kevin P.', 'Stark, Gregory V.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Rosen, Hugh', 'Oldstone, Michael B.A.']",,,,
,PMC,Activity of a phenolic dibenzylsulfide against New World arenavirus infections,http://dx.doi.org/10.3851/IMP2532,PMC3664662,,,"BACKGROUND: Junín virus (JUNV) and several other Clade B New World arenaviruses cause human disease ranging from mild febrile illness to severe viral hemorrhagic fever (HF). These viruses pose a significant threat to national security and safe and effective therapies are limited outside of Argentina, where immune plasma is the standard of care for treating JUNV infection in cases of Argentine HF. METHODS: An in vitro screen of the Chemtura library identified several compounds with activity against Tacaribe virus (TCRV), a Clade B arenavirus closely related to JUNV. Of these compounds, D746, a phenolic dibenzylsulfide, was further pursued for additional in vitro studies and evaluated in the AG129 mouse TCRV infection model. RESULTS: D746 was found to act during an early to intermediate stage of the TCRV replication cycle and micromolar range activity was confirmed by virus yield reduction assays with both TCRV and JUNV. Although intraperitoneal twice daily treatment regimens were found to be highly effective when started 2 hours prior to TCRV challenge in AG129 mice, post-exposure treatment initiated 3 days after infection was not efficacious. Interestingly, despite the pre-exposure treatment success, D746 did not reduce serum or tissue virus titers during the acute infection. Moreover, D746 elicited ascites fluid accumulation in mice during, as well as independent of, infection. CONCLUSIONS: Our findings suggest that D746 may be altering the host response to TCRV infection in AG129 mice in a way that limits pathogenesis and thereby protects mice from otherwise lethal infection in the absence of measurable reductions in viral burden.",,"['Gowen, Brian B', 'Jung, Kie-Hoon', 'Sefing, Eric J', 'Wong, Min-Hui', 'Westover, Jonna B', 'Smee, Donald F']",,,,
,PMC,Stillbirth During Infection With Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1093/infdis/jiu068,PMC4618552,,,"We conducted an epidemiologic investigation among survivors of an outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Jordan. A second-trimester stillbirth occurred during the course of an acute respiratory illness that was attributed to MERS-CoV on the basis of exposure history and positive results of MERS-CoV serologic testing. This is the first occurrence of stillbirth during an infection with MERS-CoV and may have bearing upon the surveillance and management of pregnant women in settings of unexplained respiratory illness potentially due to MERS-CoV. Future prospective investigations of MERS-CoV should ascertain pregnancy status and obtain further pregnancy-related data, including biological specimens for confirmatory testing.",,"['Payne, Daniel C.', 'Iblan, Ibrahim', 'Alqasrawi, Sultan', 'Al Nsour, Mohannad', 'Rha, Brian', 'Tohme, Rania A.', 'Abedi, Glen R.', 'Farag, Noha H.', 'Haddadin, Aktham', 'Sanhouri, Tarek Al', 'Jarour, Najwa', 'Swerdlow, David L.', 'Jamieson, Denise J.', 'Pallansch, Mark A.', 'Haynes, Lia M.', 'Gerber, Susan I.', 'Al Abdallat, Mohammad Mousa']",,,,
,PMC,Introducing ‘One Health’ as an overlooked concept in Iran,http://dx.doi.org/10.15171/ijhpm.2014.24,PMC3952533,,,,,"['Sharifi, Hamid', 'Karamouzian, Mohammad']",,,,
,PMC,Dimeric structure of pseudokinase RNase L bound to 2-5A reveals a basis for interferon induced antiviral activity,http://dx.doi.org/10.1016/j.molcel.2013.12.025,PMC3974923,,,"RNase L is an ankyrin repeat domain containing dual endoribonuclease-pseudokinase that is activated by unusual 2′,5′-oligoadenylate (2-5A) second messengers and which impedes viral infections in higher vertebrates. Despite its importance in interferon regulated antiviral innate immunity, relatively little is known about its precise mechanism of action. Here, we present a functional characterization of 2.5 Å and 3.25 Å X-ray crystal and small angle x-ray scattering structures of RNase L bound to a natural 2-5A activator with and without ADP or the non-hydrolysable ATP mimetic AMP-PNP. These studies reveal how recognition of 2-5A through interactions with the ankyrin repeat domain and the pseudokinase domain together with nucleotide binding, impose a rigid intertwined dimer configuration that is essential for RNase catalytic and anti-viral functions. The involvement of the pseudokinase domain of RNase L in 2-5A sensing, nucleotide binding, dimerization, and ribonuclease functions highlights the evolutionary adaptability of the eukaryotic protein kinase fold.",,"['Huang, Hao', 'Zeqiraj, Elton', 'Dong, Beihua', 'Jha, Babal Kant', 'Duffy, Nicole', 'Orlicky, Stephen', 'Thevakumaran, Neroshan', 'Talukdar, Manisha', 'Pillon, Monica C.', 'Ceccarelli, Derek F.', 'Wan, Leo', 'Juang, Yu-Chi', 'Mao, Daniel Y.L.', 'Gaughan, Christina', 'Brinton, Margo A.', 'Perelygin, Andrey A.', 'Kourinov, Igor', 'Guarné, Alba', 'Silverman, Robert H.', 'Sicheri, Frank']",,,,
,PMC,Insulin treatment attenuates renal ADAM17 and ACE2 shedding in diabetic Akita mice,http://dx.doi.org/10.1152/ajprenal.00516.2013,PMC3949038,,,"Angiotensin-converting enzyme 2 (ACE2) is located in several tissues and is highly expressed in renal proximal tubules, where it degrades the vasoconstrictor angiotensin II (ANG II) to ANG-(1–7). Accumulating evidence supports protective roles of ACE2 in several disease states, including diabetic nephropathy. A disintegrin and metalloprotease (ADAM) 17 is involved in the shedding of several transmembrane proteins, including ACE2. Our previous studies showed increased renal ACE2, ADAM17 expression, and urinary ACE2 in type 2 diabetic mice (Chodavarapu H, Grobe N, Somineni HK, Salem ES, Madhu M, Elased KM. PLoS One 8: e62833, 2013). The aim of the present study was to determine the effect of insulin on ACE2 shedding and ADAM17 in type 1 diabetic Akita mice. Results demonstrate increased renal ACE2 and ADAM17 expression and increased urinary ACE2 fragments (≈70 kDa) and albumin excretion in diabetic Akita mice. Immunostaining revealed colocalization of ACE2 with ADAM17 in renal tubules. Renal proximal tubular cells treated with ADAM17 inhibitor showed reduced ACE2 shedding into the media, confirming ADAM17-mediated shedding of ACE2. Treatment of Akita mice with insulin implants for 20 wk normalized hyperglycemia and decreased urinary ACE2 and albumin excretion. Insulin also normalized renal ACE2 and ADAM17 but had no effect on tissue inhibitor of metalloproteinase 3 (TIMP3) protein expression. There was a positive linear correlation between urinary ACE2 and albuminuria, blood glucose, plasma creatinine, glucagon, and triglycerides. This is the first report showing an association between hyperglycemia, cardiovascular risk factors, and increased shedding of urinary ACE2 in diabetic Akita mice. Urinary ACE2 could be used as a biomarker for diabetic nephropathy and as an index of intrarenal ACE2 status.",,"['Salem, Esam S. B.', 'Grobe, Nadja', 'Elased, Khalid M.']",,,,
,PMC,Microglia Development and function,http://dx.doi.org/10.1146/annurev-immunol-032713-120240,PMC5001846,,,"Proper development and function of the mammalian central nervous system (CNS) depend critically on the activity of parenchymal sentinels referred to as microglia. Although microglia were first described as ramified brain-resident phagocytes, research conducted over the past century has expanded considerably upon this narrow view and ascribed many functions to these dynamic CNS inhabitants. Microglia are now considered among the most versatile cells in the body, possessing the capacity to morphologically and functionally adapt to their ever-changing surroundings. Even in a resting state, the processes of microglia are highly dynamic and perpetually scan the CNS. Microglia are in fact vital participants in CNS homeostasis, and dysregulation of these sentinels can give rise to neurological disease. In this review, we discuss the exciting developments in our understanding of microglial biology, from their developmental origin to their participation in CNS homeostasis and pathophysiological states such as neuropsychiatric disorders, neurodegeneration, sterile injury responses, and infectious diseases. We also delve into the world of microglial dynamics recently uncovered using real-time imaging techniques.",,"['Nayak, Debasis', 'Roth, Theodore L.', 'McGavern, Dorian B.']",,,,
,PMC,"ACE2-Independent Action Of Presumed ACE2 Activators: Studies In Vivo, Ex Vivo and In Vitro",http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.02856,PMC4004079,,,"Angiotensin converting enzyme 2, (ACE2), is a key enzyme in the metabolism of angiotensin II. 1-[[2-(dimetilamino)ethyl]amino]-4-(hidroximetil)-7-[[(4-metilfenil)sulfonil]oxi]-9H-xantona-9 (XNT)and Diminazene (DIZE)have been reported to exert various organ-protective effects that have been attributed to activation of ACE2. To test the effect of these compounds we studied Ang II degradation in vivo and in vitro as well as their effect on ACE2 activity in vivo and in vitro. In a model of Ang II induced acute hypertension, blood pressure recovery was markedly enhanced by XNT (slope with XNT -3.26±0.2 vs.-1.6±0.2 mmHg/min without XNT, p<0.01). After Ang II infusion, neither plasma nor kidney ACE2 activity was affected by XNT. Plasma Ang II and Ang (1-7) levels also were not significantly affected by XNT. The blood pressure lowering effect of XNT seen in WT animals was also observed in ACE2 KO mice (slope with XNT -3.09±0.30 mmHg/min vs. -1.28±0.22 mmHg/min without XNT, p<0.001). These findings show that the blood pressure lowering effect of XNT in Ang II induced hypertension cannot be due to activation of ACE2. In vitro and ex vivo experiments in both mice and rat kidney confirmed a lack of enhancement of ACE2 enzymatic activity by XNT and DIZE. Moreover, Ang II degradation in vitro and ex vivo was unaffected by XNT and DIZE. We conclude that the biologic effects of these compounds are ACE2 independent and should not be attributed to activation of this enzyme.",,"['Haber, Philipp K.', 'Ye, Minghao', 'Wysocki, Jan', 'Maier, Christoph', 'Haque, Syed K.', 'Batlle, Daniel']",,,,
,PMC,The promise and challenge of high-throughput sequencing of the antibody repertoire,http://dx.doi.org/10.1038/nbt.2782,PMC4113560,,,"Efforts to determine the antibody repertoire encoded by B cells in the blood or lymphoid organs using high-throughput DNA sequencing technologies have been advancing at an extremely rapid pace and are transforming our understanding of humoral immune responses. Information gained from high-throughput DNA sequencing of immunoglobulin genes (Ig-seq) can be applied to detect B-cell malignancies with high sensitivity, to discover antibodies specific for antigens of interest, to guide vaccine development and to understand autoimmunity. Rapid progress in the development of experimental protocols and informatics analysis tools is helping to reduce sequencing artifacts, to achieve more precise quantification of clonal diversity and to extract the most pertinent biological information. That said, broader application of Ig-seq, especially in clinical settings, will require the development of a standardized experimental design framework that will enable the sharing and meta-analysis of sequencing data generated by different laboratories.",,"['Georgiou, George', 'Ippolito, Gregory C', 'Beausang, John', 'Busse, Christian E', 'Wardemann, Hedda', 'Quake, Stephen R']",,,,
,PMC,Preclinical study on combined chemo‐ and nonviral gene therapy for sensitization of melanoma using a human TNF‐alpha expressing MIDGE DNA vector,http://dx.doi.org/10.1016/j.molonc.2013.12.019,PMC5528640,,,"Nonviral gene therapy represents a realistic option for clinical application in cancer treatment. This preclinical study demonstrates the advantage of using the small‐size MIDGE® DNA vector for improved transgene expression and therapeutic application. This is caused by significant increase in transcription efficiency, but not by increased intracellular vector copy numbers or gene transfer efficiency. We used the MIDGE‐hTNF‐alpha vector for high‐level expression of hTNF‐alpha in vitro and in vivo for a combined gene therapy and vindesine treatment in human melanoma models. The MIDGE vector mediated high‐level hTNF‐alpha expression leads to sensitization of melanoma cells towards vindesine. The increased efficacy of this combination is mediated by remarkable acceleration and increase of initiator caspase 8 and 9 and effector caspase 3 and 7 activation. In the therapeutic approach, the nonviral intratumoral in vivo jet‐injection gene transfer of MIDGE‐hTNF‐alpha in combination with vindesine causes melanoma growth inhibition in association with increased apoptosis in A375 cell line or patient derived human melanoma xenotransplant (PDX) models. This study represents a proof‐of‐concept for an anticipated phase I clinical gene therapy trial, in which the MIDGE‐hTNF‐alpha vector will be used for efficient combined chemo‐ and nonviral gene therapy of malignant melanoma.",,"['Kobelt, Dennis', 'Aumann, Jutta', 'Schmidt, Manuel', 'Wittig, Burghardt', 'Fichtner, Iduna', 'Behrens, Diana', 'Lemm, Margit', 'Freundt, Greta', 'Schlag, Peter M.', 'Walther, Wolfgang']",,,,
,PMC,Importance of Internet Surveillance in Public Health Emergency Control and Prevention: Evidence From a Digital Epidemiologic Study During Avian Influenza A H7N9 Outbreaks,http://dx.doi.org/10.2196/jmir.2911,PMC3906895,24440770,CC BY,"BACKGROUND: Outbreaks of human infection with a new avian influenza A H7N9 virus occurred in China in the spring of 2013. Control and prevention of a new human infectious disease outbreak can be strongly affected by public reaction and social impact through the Internet and social media. OBJECTIVE: This study aimed to investigate the potential roles of Internet surveillance in control and prevention of the human H7N9 outbreaks. METHODS: Official data for the human H7N9 outbreaks were collected via the China National Health and Family Planning Committee website from March 31 to April 24, 2013. We obtained daily posted and forwarded number of blogs for the keyword “H7N9” from Sina microblog website and a daily Baidu Attention Index (BAI) from Baidu website, which reflected public attention to the outbreak. Rumors identified and confirmed by the authorities were collected from Baidu search engine. RESULTS: Both daily posted and forwarded number and BAI for keyword H7N9 increased quickly during the first 3 days of the outbreaks and remained at a high level for 5 days. The total daily posted and forwarded number for H7N9 on Sina microblog peaked at 850,000 on April 3, from zero blogs before March 31, increasing to 97,726 on April 1 and to 370,607 on April 2, and remaining above 500,000 from April 5-8 before declining to 208,524 on April 12. The total daily BAI showed a similar pattern of change to the total daily posted and forwarded number over time from March 31 to April 12. When the outbreak locations spread, especially into other areas of the same province/city and the capital, Beijing, daily posted and forwarded number and BAI increased again to a peak at 368,500 and 116,911, respectively. The median daily BAI during the studied 25 days was significantly higher among the 7 provinces/cities with reported human H7N9 cases than the 2 provinces without any cases (P<.001). So were the median daily posted and forwarded number and daily BAI in each province/city except Anhui province. We retrieved a total of 32 confirmed rumors spread across 19 provinces/cities in China. In all, 84% (27/32) of rumors were disseminated and transmitted by social media. CONCLUSIONS: The first 3 days of an epidemic is a critical period for the authorities to take appropriate action through Internet surveillance to prevent and control the epidemic, including preparation of personnel, technology, and other resources; information release; collection of public opinion and reaction; and clarification, prevention, and control of rumors. Internet surveillance can be used as an efficient and economical tool to prevent and control public health emergencies, such as H7N9 outbreaks.",2014 Jan 17,"['Gu, Hua', 'Chen, Bin', 'Zhu, Honghong', 'Jiang, Tao', 'Wang, Xinyi', 'Chen, Lei', 'Jiang, Zhenggang', 'Zheng, Dawei', 'Jiang, Jianmin']",J Med Internet Res,,,
,PMC,Successful management of Panton-Valentine leukocidine-positive necrotising pneumonia and A/H1N1(2009) influenzavirus coinfection in adult,http://dx.doi.org/10.1136/bcr-2013-201120,PMC3902338,,,"This paper presents a case of community-acquired necrotising pneumonia due to Panton-Valentine leukocidine-positive methicillin-susceptible Staphylococcus aureus and A/H1N1(2009) influenzavirus co-infection in a 26-year-old woman. Despite the presence of pejorative prognostic factors, the clinical course of the patient was favourable.",,"['Riedweg-Moreno, Karena', 'Wallet, Frederic', 'Blazejewski, Caroline', 'Goffard, Anne']",,,,
,PMC,Mechanisms shaping the naïve T cell repertoire in the elderly - Thymic involution or peripheral homeostatic proliferation?,http://dx.doi.org/10.1016/j.exger.2014.01.005,PMC4096164,,,"The ability of the human immune system to repel infections is drastically diminished with age. Elderly individuals are more susceptible to new threats and are less able to control endogenous infections. The thymus, which is the sole source of new T cells, has been proposed as a target for regenerative efforts to improve immune competence, as thymic activity is dramatically reduced after puberty. In this review, we review the role of the thymus in the maintenance of T cell homeostasis throughout life and contrast the differences in mice and humans. We propose that in humans, lack of thymic T cell generation does not explain a decline in T cell receptor diversity nor would thymic rejuvenation restore diversity. Initial studies using next generation sequencing are beginning to establish lower boundaries of T cell receptor diversity. With increasing sequencing depth and the development of new statistical models, we are now in the position to test this model and to assess the impact of age on T cell diversity and clonality.",,"['Qi, Qian', 'Zhang, David W.', 'Weyand, Cornelia M.', 'Goronzy, Jörg J.']",,,,
,PMC,Is hepatitis B-virucidal validation of biocides possible with the use of surrogates?,http://dx.doi.org/10.3748/wjg.v20.i2.436,PMC3923018,,,"The hepatitis B virus (HBV) is considered to be a major public health problem worldwide, and a significant number of reports on nosocomial outbreaks of HBV infections have been reported. Prevention of indirect HBV transmission by contaminated objects is only possible through the use of infection-control principles, including the use of chemical biocides, which are proven to render the virus non-infectious. The virucidal activity of biocides against HBV cannot be predicted; therefore, validation of the virucidal action of disinfectants against HBV is essential. However, feasible HBV infectivity assays have not yet been established. Thus, surrogate models have been proposed for testing the efficacy of biocides against HBV. Most of these assays do not correlate with HBV infectivity. Currently, the most promising and feasible assay is the use of the taxonomically related duck hepatitis B virus (DHBV), which belongs to the same Hepadnaviridae virus family. This paper reviews the application of DHBV, which can be propagated in vitro in primary duck embryonic hepatocytes, for the testing of biocides and describes why this model can be used as reliable method to evaluate disinfectants for efficacy against HBV. The susceptibility levels of important biocides, which are often used as ingredients for commercially available disinfectants, are also described.",,"Sauerbrei, Andreas",,,,
,PMC,A Novel Molecular Microbiologic Technique for the Rapid Diagnosis of Microbial Invasion of the Amniotic Cavity and Intra-Amniotic Infection in Preterm Labor with Intact Membranes,http://dx.doi.org/10.1111/aji.12189,PMC3954440,,,"OBJECTIVE: The major challenges in using amniotic fluid (AF) cultivation techniques to diagnose microbial invasion of the amniotic cavity (MIAC) are: 1) several days are typically required to obtain results, and 2) many organisms implicated in the pathogenesis of human disease are difficult to culture. Here, we compare the performance of AF culture with a novel technique for the diagnosis of MIAC that can provide results within eight hours by combining broad-range real-time polymerase chain reaction with electrospray ionization mass spectrometry (PCR/ESI-MS) to identify and quantify genomic material from bacteria and viruses in AF. METHODS: AF samples obtained by transabdominal amniocentesis from 142 women with preterm labor (PTL) and intact membranes were analyzed using cultivation techniques (aerobic, anaerobic and genital mycoplasmas) as well as PCR/ESI-MS. The prevalence and relative magnitude of intra-amniotic inflammation [AF Interleukin 6 (IL-6) concentration ≥ 2.6 ng/mL], acute histologic chorioamnionitis, spontaneous preterm delivery, and perinatal mortality were examined according to the results of these two tests. RESULTS: 1) The prevalence of MIAC in patients with preterm labor and intact membranes was 7% using standard cultivation techniques and 12% using PCR/ESI-MS; 2) seven of ten patients with positive AF culture also had positive PCR/ESI-MS [≥17 genome equivalents per PCR reaction well (GE/well)] 3) patients with positive PCR/ESI-MS (≥17 GE/well) and negative AF cultures had significantly higher rates of intra-amniotic inflammation and histologic acute chorioamnionitis, shorter intervals to delivery [median (interquartile range-IQR)], and offspring at higher risk of perinatal mortality, than women with both tests negative [90% (9/10) vs. 32% (39/122); (p<0.001); 70% (7/10) vs. 35% (39/112); (p=0.04); 1 (IQR: <1 – 2) days vs. 25 (IQR: 5 – 51) days; (p=0.002); OR: 5.6; 95% CI: 1.4 – 22, respectively]; 5) there were no significant differences in these factors between patients with positive PCR/ESI-MS (≥17 GE/well) who had negative AF cultures compared to those with positive AF cultures; and 6) PCR/ESI-MS detected genomic material from viruses in two patients (1.4%). CONCLUSION: 1) Rapid diagnosis of intra-amniotic infection is possible using PCR/ESI-MS, which can provide results within 8 hours; 2) the combined use of biomarkers of inflammation and PCR/ESI-MS allows for the rapid identification of specific bacteria and viruses in women with preterm labor and intra-amniotic infection; and 3) this approach may allow for administration of timely and specific interventions to reduce morbidity attributed to infection-induced preterm birth.",,"['Romero, Roberto', 'Miranda, Jezid', 'Chaiworapongsa, Tinnakorn', 'Chaemsaithong, Piya', 'Gotsch, Francesca', 'Dong, Zhong', 'Ahmed, Ahmed I.', 'Yoon, Bo Hyun', 'Hassan, Sonia', 'Kim, Chong J.', 'Korzeniewski, Steven J.', 'Yeo, Lami']",,,,
,PMC,The role of pro-resolution lipid mediators in infectious disease,http://dx.doi.org/10.1111/imm.12206,PMC3904237,,,"Inflammation is an essential host defence against infection, but can be damaging when excessive. Resolution of inflammation is an active process, and the pro-resolution effects of lipoxins, resolvins and protectins have received significant interest. Here, we review emerging data on the role of these lipid mediators in infectious disease. Lipoxins influence host control of Mycobacterium tuberculosis, Toxoplasma gondii, Trypanosoma cruzi and Plasmodium berghei cerebral malaria in mice. Their effects are protective in toxoplasmosis, T. cruzi infection and cerebral malaria but detrimental in tuberculosis; related to the balance between pathogen-control and excessive immune response. Topical lipoxin abrogates the tissue damage seen in a rabbit model of Porphyromonas gingivalis periodontitis. The increased virulence of H5N1 influenza A virus in mice correlates with reduced expression of SOCS2, required to mediate the effects of lipoxin. Mice unable to synthesize lipoxin suffer increased lung pathology during respiratory syncytial virus infection. Protectin suppresses influenza A virus replication in vitro and increases survival in a mouse model of severe influenza infection. Resolvins were investigated in a number of animal models of systemic bacterial infection, and were found to enhance phagocytic clearance of bacteria, reduce inflammation severity, promote neutrophil apoptosis, modulate neutrophil chemotaxis and importantly, reduce mortality. Interestingly, resolvin also enhances the antibacterial effect of ciprofloxacin and vancomycin. Topical resolvin application reduces the severity of herpes simplex virus ocular infection in mice. If the effects of these mediators translate from pre-clinical studies into successful clinical trials, they represent promising new strategies in managing infectious disease.",,"['Russell, Clark D', 'Schwarze, Jürgen']",,,,
,PMC,Functional Cross-talk between Distant Domains of Chikungunya Virus Non-structural Protein 2 Is Decisive for Its RNA-modulating Activity,http://dx.doi.org/10.1074/jbc.M113.503433,PMC3937639,,,"Chikungunya virus (CHIKV) non-structural protein 2 (nsP2) is a multifunctional protein that is considered a master regulator of the viral life cycle and a main viral factor responsible for cytopathic effects and subversion of antiviral defense. The C-terminal part of nsP2 possesses protease activity, whereas the N-terminal part exhibits NTPase and RNA triphosphatase activity and is proposed to have helicase activity. Bioinformatics analysis classified CHIKV nsP2 into helicase superfamily 1. However, the biochemical significance of a coexistence of two functionally unrelated modules in this single protein remains unknown. In this study, recombinant nsP2 demonstrated unwinding of double-stranded RNA in a 5′–3′ directionally biased manner and RNA strand annealing activity. Comparative analysis of NTPase and helicase activities of wild type nsP2 with enzymatic capabilities of different truncated or N-terminally extended variants of nsP2 revealed that the C-terminal part of the protein is indispensable for helicase functionality and presumably provides a platform for RNA binding, whereas the N-terminal-most region is apparently involved in obtaining a conformation of nsP2 that allows for its maximal enzymatic activities. The establishment of the protocols for the production of biochemically active CHIKV nsP2 and optimization of the parameters for helicase and NTPase assays are expected to provide the starting point for a further search of possibilities for therapeutic interventions to suppress alphaviral infections.",,"['Das, Pratyush Kumar', 'Merits, Andres', 'Lulla, Aleksei']",,,,
,PMC,Family caregivers in public tertiary care hospitals in Bangladesh: Risks and opportunities for infection control,http://dx.doi.org/10.1016/j.ajic.2013.09.012,PMC4681270,,,"BACKGROUND: Family caregivers are integral to patient care in Bangladeshi public hospitals. This study explored family caregivers’ activities and their perceptions and practices related to disease transmission and prevention in public hospitals. METHODS: Trained qualitative researchers conducted a total of 48 hours of observation in 3 public tertiary care hospitals and 12 in-depth interviews with family caregivers. RESULTS: Family caregivers provided care 24 hours a day, including bedside nursing, cleaning care, and psychologic support. During observations, family members provided 2,065 episodes of care giving, 75% (1,544) of which involved close contact with patients. We observed family caregivers washing their hands with soap on only 4 occasions. The majority of respondents said diseases are transmitted through physical contact with surfaces and objects that have been contaminated with patient secretions and excretions, and avoiding contact with these contaminated objects would help prevent disease. CONCLUSION: Family caregivers are at risk for hospital-acquired infection from their repeated exposure to infectious agents combined with their inadequate hand hygiene and knowledge about disease transmission. Future research should explore potential strategies to improve family caregivers’ knowledge about disease transmission and reduce family caregiver exposures, which may be accomplished by improving care provided by health care workers.",,"['Islam, M. Saiful', 'Luby, Stephen P.', 'Sultana, Rebeca', 'Rimi, Nadia Ali', 'Zaman, Rashid Uz', 'Uddin, Main', 'Nahar, Nazmun', 'Rahman, Mahmudur', 'Hossain, M. Jahangir', 'Gurley, Emily S.']",,,,
,PMC,Single-Molecule Measurements of the CCR5 mRNA Unfolding Pathways,http://dx.doi.org/10.1016/j.bpj.2013.09.036,PMC3907219,,,"Secondary or tertiary structure in an mRNA, such as a pseudoknot, can create a physical barrier that requires the ribosome to generate additional force to translocate. The presence of such a barrier can dramatically increase the probability that the ribosome will shift into an alternate reading frame, in which a different set of codons is recognized. The detailed biophysical mechanism by which frameshifting is induced remains unknown. Here we employ optical trapping techniques to investigate the structure of a −1 programmed ribosomal frameshift (−1 PRF) sequence element located in the CCR5 mRNA, which encodes a coreceptor for HIV-1 and is, to our knowledge, the first known human −1 PRF signal of nonviral origin. We begin by presenting a set of computationally predicted structures that include pseudoknots. We then employ what we believe to be new analytical techniques for measuring the effective free energy landscapes of biomolecules. We find that the −1 PRF element manifests several distinct unfolding pathways when subject to end-to-end force, one of which is consistent with a proposed pseudoknot conformation, and another of which we have identified as a folding intermediate. The dynamic ensemble of conformations that CCR5 mRNA exhibits in the single-molecule experiments may be a significant feature of the frameshifting mechanism.",,"['de\xa0Messieres, Michel', 'Chang, Jen-Chien', 'Belew, Ashton\xa0Trey', 'Meskauskas, Arturas', 'Dinman, Jonathan\xa0D.', 'La\xa0Porta, Arthur']",,,,
,PMC,"Human pathogenic bacteria, fungi, and viruses in Drosophila: Disease modeling, lessons, and shortcomings",http://dx.doi.org/10.4161/viru.27524,PMC3956501,,,"Drosophila has been the invertebrate model organism of choice for the study of innate immune responses during the past few decades. Many Drosophila–microbe interaction studies have helped to define innate immunity pathways, and significant effort has been made lately to decipher mechanisms of microbial pathogenesis. Here we catalog 68 bacterial, fungal, and viral species studied in flies, 43 of which are relevant to human health. We discuss studies of human pathogens in flies revealing not only the elicitation and avoidance of immune response but also mechanisms of tolerance, host tissue homeostasis, regeneration, and predisposition to cancer. Prominent among those is the emerging pattern of intestinal regeneration as a defense response induced by pathogenic and innocuous bacteria. Immunopathology mechanisms and many microbial virulence factors have been elucidated, but their relevance to human health conventionally necessitates validation in mammalian models of infection.",,"['Panayidou, Stavria', 'Ioannidou, Eleni', 'Apidianakis, Yiorgos']",,,,
,PMC,Correspondence (letter to the editor): The Crucial Role of Molecular Diagnostics,http://dx.doi.org/10.3238/arztebl.2014.0010a,PMC3948014,,,,,"['Panning, Marcus', 'Huzly, Daniela', 'Hengel, Hartmut', 'V. Kern, Winfried', 'Dettenkofer, Markus']",,,,
,PMC,Functional Comorbidity Index in Sleep Apnea,http://dx.doi.org/10.1177/0194599813518164,PMC5940928,,,"OBJECTIVES: 1) Measure the association between the Functional Comorbidity Index (range 0–18) and physical function health status (SF-36 Physical Function domain), general physical health status (SF-36 Physical Component Score), and general mental health status (SF-36 Mental Component Score) outcome measures in a cohort of sleep apnea patients. 2) Test if the Functional Comorbidity Index is more strongly associated (a better predictor) than the well-known Charlson Comorbidity Index (range 0–37) with these SF-36 outcome measures. STUDY DESIGN: Cross-sectional study. SETTING: University of Washington Sleep Center. SUBJECTS AND METHODS: In a cohort of newly diagnosed obstructive sleep apnea patients (N = 233), we obtained scores for the Functional Comorbidity Index, Charlson Comorbidity Index, and SF-36. We calculated Spearman correlations and adjusted coefficients of determination (R(2)) with multiple linear regression, adjusted for demographic and health covariates. Bootstrapping generated R(2) distributions for statistical comparison. RESULTS: Functional Comorbidity Index scores (mean±standard deviation 2.4±1.7) were more widely distributed than Charlson Comorbidity Index scores (0.7±1.4). The Functional Comorbidity Index was significantly correlated with SF-36 Physical Function (−0.53, p<0.001), Physical Component Score (−0.44, p<0.001), and Mental Component Score (−0.38, p<0.001). The Functional Comorbidity Index was a better predictor than the Charlson Comorbidity Index of SF-36 Physical Function (R(2) mean±standard error 0.27±0.05 versus 0.17±0.05, p<0.001), Physical Component Score (0.23±0.05 versus 0.17±0.05, p<0.001), and Mental Component Score (0.23±0.05 versus 0.13±0.05, p<0.001). CONCLUSION: The Functional Comorbidity Index is a more robust predictor of general health status than the Charlson Comorbidity Index in obstructive sleep apnea patients.",,"['Levine, Corinna G.', 'Weaver, Edward M.']",,,,
,PMC,"Tumour immunogenicity, antigen presentation and immunological barriers in cancer immunotherapy",http://dx.doi.org/10.1155/2014/734515,PMC3952940,,,"Since the beginning of the 20(th) century, scientists have tried to stimulate the anti-tumour activities of the immune system to fight against cancer. However, the scientific effort devoted on the development of cancer immunotherapy has not been translated into the expected clinical success. On the contrary, classical anti-neoplastic treatments such as surgery, radiotherapy and chemotherapy are the first line of treatment. Nevertheless, there is compelling evidence on the immunogenicity of cancer cells, and the capacity of the immune system to expand cancer-specific effector cytotoxic T cells. However, the effective activation of anti-cancer T cell responses strongly depends on efficient tumour antigen presentation from professional antigen presenting cells such as dendritic cells (DCs). Several strategies have been used to boost DC antigen presenting functions, but at the end cancer immunotherapy is not as effective as would be expected according to preclinical models. In this review we comment on these discrepancies, focusing our attention on the contribution of regulatory T cells and myeloid-derived suppressor cells to the lack of therapeutic success of DC-based cancer immunotherapy.",,"Escors, David",,,,
,PMC,The CD200–CD200R1 Inhibitory Signaling Pathway: Immune Regulation and Host–Pathogen Interactions,http://dx.doi.org/10.1016/B978-0-12-800100-4.00005-2,PMC4617684,,,"The CD200:CD200R1 inhibitory signaling pathway has been implicated in playing a prominent role in limiting inflammation in a wide range of inflammatory diseases. CD200R1 signaling inhibits the expression of proinflammatory molecules including tumor necrosis factor, interferons, and inducible nitric oxide synthase in response to selected stimuli. Unsurprisingly, due to the regulatory role that CD200R1 plays in multiple inflammatory pathways, an increasing number of parasitic, bacterial, and viral pathogens exploit this pathway to suppress host defenses. A complete understanding of the pathways regulated by CD200R1 signaling and the diverse mechanisms that pathogens have evolved to manipulate the CD200:CD200R1 pathway can help identify clinical situations where targeting this interaction can be of therapeutic benefit. In this review, we compare CD200R1 to other pathogen-targeted inhibitory receptors and highlight how this signaling pathway is utilized by a diverse number of pathogens and, therefore, may represent a novel targeting strategy for the treatment of infectious diseases.",,"['Vaine, Christine A.', 'Soberman, Roy J.']",,,,
,PMC,Investigation of an Outbreak of Acute Respiratory Disease in Côte D'Ivoire in April 2007,,PMC4325357,,,"BACKGROUND: This study aim was to investigate an outbreak of human cases of unexplained influenza-like illness and fatal acute respiratory infection (ARI), with simultaneous poultry illness and high mortality raising concerns of possible influenza A (H5N1), virus in Cote d'Ivoire in February and March 2007. MATERIALS AND METHODS: To investigate the outbreak, we conducted active surveillance in the community and reviewed health registries. Persons meeting the case definition were asked to provide nasopharyngeal specimens. On the basis of clinical and epidemiological information, specimens were tested using conventional RT-PCR for the M gene of the influenza viruses and hemagglutinin H5 of avian influenza A (H5N1), virus; negative samples were tested for other respiratory viruses. Specimens from healthy animals were also collected. RESULTS: Between October 2006, and February 2007, 104 suspected cases of Acute Respiratory Disease that included; 31 deaths recorded. We collected and tested 73 nasopharyngeal specimens; of which, 2, were positive for human Coronavirus OC43 and 1 for influenza C virus. No pathogens were identified in animal specimens. CONCLUSIONS: The investigation quickly ruled out influenza A (H5N1), virus as the cause and found laboratory-confirmed cases of influenza C virus and human Coronavirus OC 43 for the first time in both Côte d'Ivoire and in a Sub-Saharan African country. However we were not able to show that these viruses caused the outbreak. Monitoring of influenza viruses must be a priority but other respiratory viruses and non-viral causes may be of interest too.",,"['Ekaza, Euloge', 'Kadjo, Hervé Adjé', 'Coulibaly, Daouda', 'Koutouan, Guy Georges Mayet', ""Coulibaly-N'golo, Grossmann Marie-David"", 'Kouakou, Bertin', 'Talla Nzussouo, Ndahwouh', 'Olsen, Sonja Julia', 'Ekra, Daniel Kouadio', 'Akoua-Koffi, Chantal Gnankon', 'Gilbernair, Elia Aka', 'Bretin-Dosso, Mireille Carmen']",,,,
,PMC,The High Cost of Fidelity,http://dx.doi.org/10.1089/aid.2013.0153,PMC3887412,,,"The notoriously low fidelity of HIV-1 replication is largely responsible for the virus's rapid mutation rate, facilitating escape from immune or drug control. The error-prone activity of the viral reverse transcriptase (RT) is predicted to be the most influential mechanism for generating mutations. The low fidelity of RT has been successfully exploited by nucleoside and nucleotide analogue reverse transcriptase inhibitors (NRTIs) that halt viral replication upon incorporation. Consequently, drug-resistant strains have arisen in which the viral RT has an increased fidelity of replication, thus reducing analogue incorporation. Higher fidelity, however, impacts on viral fitness. The appearance of compensatory mutations in combination with higher fidelity NRTI resistance mutations and the subsequent reversion of NRTI-resistant mutations upon cessation of antiretroviral treatment lend support to the notion that higher fidelity exacts a fitness cost. Potential mechanisms for reduced viral fitness are a smaller pool of mutant strains available to respond to immune or drug pressure, slower rates of replication, and a limitation to the dNTP tropism of the virus. Unraveling the relationship between replication fidelity and fitness should lead to a greater understanding of the evolution and control of HIV.",,"['Lloyd, Sarah B.', 'Kent, Stephen J.', 'Winnall, Wendy R.']",,,,
,PMC,Histopathological Evaluation of the Diversity of Cells Susceptible to H5N1 Virulent Avian Influenza Virus,http://dx.doi.org/10.1016/j.ajpath.2013.10.004,PMC3873492,,,"Patients infected with highly pathogenic avian influenza A H5N1 viruses (H5N1 HPAIV) show diffuse alveolar damage. However, the temporal progression of tissue damage and repair after viral infection remains poorly defined. Therefore, we assessed the sequential histopathological characteristics of mouse lung after intranasal infection with H5N1 HPAIV or H1N1 2009 pandemic influenza virus (H1N1 pdm). We determined the amount and localization of virus in the lung through IHC staining and in situ hybridization. IHC used antibodies raised against the virus protein and antibodies specific for macrophages, type II pneumocytes, or proliferating cell nuclear antigen. In situ hybridization used RNA probes against both viral RNA and mRNA encoding the nucleoprotein and the hemagglutinin protein. H5N1 HPAIV infection and replication were observed in multiple lung cell types and might result in rapid progression of lung injury. Both type II pneumocytes and macrophages proliferated after H5N1 HPAIV infection. However, the abundant macrophages failed to block the viral attack, and proliferation of type II pneumocytes failed to restore the damaged alveoli. In contrast, mice infected with H1N1 pdm exhibited modest proliferation of type II pneumocytes and macrophages and slight alveolar damage. These results suggest that the virulence of H5N1 HPAIV results from the wide range of cell tropism of the virus, excessive virus replication, and rapid development of diffuse alveolar damage.",,"['Ogiwara, Haru', 'Yasui, Fumihiko', 'Munekata, Keisuke', 'Takagi-Kamiya, Asako', 'Munakata, Tsubasa', 'Nomura, Namiko', 'Shibasaki, Futoshi', 'Kuwahara, Kazuhiko', 'Sakaguchi, Nobuo', 'Sakoda, Yoshihiro', 'Kida, Hiroshi', 'Kohara, Michinori']",,,,
,PMC,Rethinking Public Health: Promoting Public Engagement Through a New Discursive Environment,http://dx.doi.org/10.2105/AJPH.2013.301638,PMC3910054,,,"I reexamine the notion of public health after reviewing critiques of the prevalent individualistic conception of health. I argue that public health should mean not only the health of the public but also health in the public and by the public, and I expound on the social contingency of health and highlight the importance of the interpersonal dimensions of health conditions and health promotion efforts. Promoting public health requires activating health-enhancing communicative behaviors (such as interpersonal advocacy and mutual responsibility taking) in addition to individual behavioral change. To facilitate such communicative behaviors, it is imperative to first construct a new discursive environment in which to think and talk about health in a language of interdependence and collective efforts.",,"Sun, Ye",,,,
,PMC,Activity of and Effect of Subcutaneous Treatment with the Broad-Spectrum Antiviral Lectin Griffithsin in Two Laboratory Rodent Models,http://dx.doi.org/10.1128/AAC.01407-13,PMC3910741,,,"Griffithsin (GRFT) is a red-alga-derived lectin that binds the terminal mannose residues of N-linked glycans found on the surface of human immunodeficiency virus type 1 (HIV-1), HIV-2, and other enveloped viruses, including hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus (SARS-CoV), and Ebola virus. GRFT displays no human T-cell mitogenic activity and does not induce production of proinflammatory cytokines in treated human cell lines. However, despite the growing evidence showing the broad-spectrum nanomolar or better antiviral activity of GRFT, no study has reported a comprehensive assessment of GRFT safety as a potential systemic antiviral treatment. The results presented in this work show that minimal toxicity was induced by a range of single and repeated daily subcutaneous doses of GRFT in two rodent species, although we noted treatment-associated increases in spleen and liver mass suggestive of an antidrug immune response. The drug is systemically distributed, accumulating to high levels in the serum and plasma after subcutaneous delivery. Further, we showed that serum from GRFT-treated animals retained antiviral activity against HIV-1-enveloped pseudoviruses in a cell-based neutralization assay. Overall, our data presented here show that GRFT accumulates to relevant therapeutic concentrations which are tolerated with minimal toxicity. These studies support further development of GRFT as a systemic antiviral therapeutic agent against enveloped viruses, although deimmunizing the molecule may be necessary if it is to be used in long-term treatment of chronic viral infections.",,"['Barton, Christopher', 'Kouokam, J. Calvin', 'Lasnik, Amanda B.', 'Foreman, Oded', 'Cambon, Alexander', 'Brock, Guy', 'Montefiori, David C.', 'Vojdani, Fakhrieh', 'McCormick, Alison A.', ""O'Keefe, Barry R."", 'Palmer, Kenneth E.']",,,,
,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.14.010114,PMC3865555,,,,,,,,,
,PMC,De l’observation clinique à la découverte clinique: Le défi de la recherche en médecine familiale,,PMC3994817,,,,,"['Pimlott, Nicholas', 'Upshur, Ross E.G.']",,,,
,PMC,From clinical observation to clinical discovery: The challenge for family medicine research,,PMC3994798,,,,,"['Pimlott, Nicholas', 'Upshur, Ross E.G.']",,,,
,PMC,The respiratory presentation of severe combined immunodeficiency in two Mennonite children at a tertiary centre highlighting the importance of recognizing this pediatric emergency,,PMC3938231,,,"Severe combined immunodeficiency (SCID) is considered to be a pediatric emergency, with respiratory distress being the most common presenting symptom. The authors present two cases of SCID in children <4 months of age with respiratory distress at a tertiary care centre due to a recently described homozygous CD3 delta mutation found only in the Mexican Mennonite population. Failure to respond to broad-spectrum antibiotics prompted investigation for possible SCID. Bronchial alveolar lavage fluid from both patients grew Pneumocystis jiroveci, and flow cytometry revealed absent T cells. The CD3 delta gene is believed to be important in T cell differentiation and maturation. The present article reminds pediatricians and pediatric respirologists that the key to diagnosing SCID is to have a high index of suspicion if there is poor response to conventional therapies.",,"['Lam, Simon', 'Kavadas, Fotini D', 'Haider, Seemab', 'Noseworthy, Mary E']",,,,
,PMC,Dengue Virus Subverts the Interferon Induction Pathway via NS2B/3 Protease-IκB Kinase ε Interaction,http://dx.doi.org/10.1128/CVI.00500-13,PMC3910921,,,"Dengue is the world's most common mosquito-borne viral infection and a leading cause of morbidity throughout the tropics and subtropics. Viruses are known to evade the establishment of an antiviral state by regulating the activation of interferon regulatory factor 3 (IRF3), a critical transcription factor in the alpha/beta interferon induction pathway. Here, we show that dengue virus (DENV) circumvents the induction of the retinoic acid-inducible gene I-like receptor (RLR) pathway during infection by blocking serine 386 phosphorylation and nuclear translocation of IRF3. This effect is associated with the expression of nonstructural 2B/3 protein (NS2B/3) protease in human cells. Using interaction assays, we found that NS2B/3 interacts with the cellular IκB kinase ε (IKKε). Docking computational analysis revealed that in this interaction, NS2B/3 masks the kinase domain of IKKε and potentially affects its functionality. This observation is supported by the DENV-associated inhibition of the kinase activity of IKKε. Our data identify IKKε as a novel target of DENV NS2B/3 protease.",,"['Angleró-Rodríguez, Yesseinia I.', 'Pantoja, Petraleigh', 'Sariol, Carlos A.']",,,,
,PMC,Human FcR Polymorphism and Disease,http://dx.doi.org/10.1007/978-3-319-07911-0_13,PMC4209745,,,"Fc receptors play a central role in maintaining the homeostatic balance in the immune system. Our knowledge of the structure and function of these receptors and their naturally occurring polymorphisms, including single nucleotide polymorphisms and/or copy number variations, continues to expand. Through studies of their impact on human biology and clinical phenotype, the contributions of these variants to the pathogenesis, progression, and/or treatment outcome of many diseases that involve immunoglobulin have become evident. They affect susceptibility to bacterial and viral pathogens, constitute as risk factors for IgG or IgE mediated inflammatory diseases, and impact the development of many autoimmune conditions. In this chapter, we will provide an overview of these genetic variations in classical FcγRs, FcRLs, and other Fc receptors, as well as challenges in achieving an accurate and comprehensive understanding of the FcR polymorphisms and genomic architecture.",,"['Li, Xinrui', 'Gibson, Andrew W.', 'Kimberly, Robert P.']",,,,
,PMC,Regulation of the trafficking and antiviral activity of IFITM3 by post-translational modifications,http://dx.doi.org/10.2217/fmb.14.65,PMC4254935,,,"IFITM3 restricts cellular infection by multiple important viral pathogens, and is particularly critical for the innate immune response against influenza virus. Expression of IFITM3 expands acidic endolysosomal compartments and prevents fusion of endocytosed viruses, leading to their degradation. This small, 133 amino acid, antiviral protein is controlled by at least four distinct post-translational modifications. Positive regulation of IFITM3 antiviral activity is provided by S-palmitoylation, while negative regulatory mechanisms include lysine ubiquitination, lysine methylation and tyrosine phosphorylation. Herein, we describe specific insights into IFITM3 trafficking and activity that were provided by studies of IFITM3 post-translational modifications, and discuss evidence suggesting that IFITM3 adopts multiple membrane topologies involving at least one intramembrane domain in its antivirally active conformation.",,"['Chesarino, Nicholas M', 'McMichael, Temet M', 'Yount, Jacob S']",,,,
,PMC,"Countermeasure development for Rift Valley fever: deletion, modification or targeting of major virulence factor NSs",http://dx.doi.org/10.2217/fvl.13.117,PMC4043376,,,"Rift Valley fever (RVF) is a mosquito-borne zoonotic disease characterized by a high rate of abortion in ruminants, and febrile illness, hemorrhagic fever, retinitis and encephalitis in humans. RVF is caused by the RVF virus (RVFV), belonging to the genus Phlebovirus of the family Bunyaviridae. RVFV encodes a major virulence factor, NSs, which is dispensable for viral replication, yet required for evasion of host innate immune responses. RVFV NSs inhibits host gene upregulation at the transcriptional level, while promoting viral translation in the cytoplasm. In this article, we summarize the virology and pathology of RVF, and countermeasure development for RVF, with emphasis on NSs function and applications.",,"['Lihoradova, Olga', 'Ikegami, Tetsuro']",,,,
,PMC,Neuroepidemiology and the epidemiology of viral infections of the nervous system,http://dx.doi.org/10.1016/B978-0-444-53488-0.00003-1,PMC4732278,,,,,"Sejvar, James",,,,
,PMC,Adaptive immune response to viral infections in the central nervous system,http://dx.doi.org/10.1016/B978-0-444-53488-0.00010-9,PMC4370180,,,"Historically, the central nervous system (CNS) has been considered to be an immunologically privileged site within the body (Bailey et al., 2006; Galea et al. 2007; Engelhardt, 2008; Prendergast and Anderton, 2009). By definition, immunologically privileged sites, to include the brain, cornea, testis, and pregnant uterus, have a reduced/delayed ability to reject foreign tissue grafts compared to conventional sites within the body, such as skin (Streilein, 2003; Bailey et al., 2006; Carson et al., 2006; Mrass and Weninger, 2006; Kaplan and Niederkorn, 2007). In addition and conversely, tissue grafts prepared from immunologically privileged sites have increased survival, compared to tissue grafts prepared from conventional sites, when implanted at conventional sites (Streilein, 2003). The imune privilege of the CNS has been shown to be confined to the parenchyma, whereas the immune reactivity of the meninges and the ventricles, containing the choroid plexus, cerebrospinal fluid (CSF), and the circumventricular organs, is similar to conventionalsites (Carson et al., 2006; Engelhardt, 2006; Galea et al., 2007). This confinement of the imm une privilege to the parenchyma has also been demonstrated for experimental influenza virus infection in which confinement of the infection to the brain parenchyma did not result in efficient immune system priming whereas infection of the CSF elicited a virus-specific immune response comparable to that of intranasal infection (Stevenson et al. 1997). An important functional aspect of immune privilege is that damage due to the immune response and inflammation is limited within sensitive organs containing cell types that regenerate poorly, such as neurons within the brain (Mrass and Weninger, 2006; Galea et al.. 2007; Kaplan and Niederkorn, 2007).",,"['LIBBEY, JANE E.', 'FUJINAMI, ROBERT S.']",,,,
,PMC,MBL2 Variations and Malaria Susceptibility in Indian Populations,http://dx.doi.org/10.1128/IAI.01041-13,PMC3911836,,,"Human mannose-binding lectin (MBL) encoded by the MBL2 gene is a pattern recognition protein and has been associated with many infectious diseases, including malaria. We sought to investigate the contribution of functional MBL2 gene variations to Plasmodium falciparum malaria in well-defined cases and in matched controls. We resequenced the 8.7 kb of the entire MBL2 gene in 434 individuals clinically classified with malaria from regions of India where malaria is endemic. The study cohort included 176 patients with severe malaria, 101 patients with mild malaria, and 157 ethnically matched asymptomatic individuals. In addition, 830 individuals from 32 socially, linguistically, and geographically diverse endogamous populations of India were investigated for the distribution of functional MBL2 variants. The MBL2 −221C (X) allelic variant is associated with increased risk of malaria (mild malaria odds ratio [OR] = 1.9, corrected P value [P(Corr)] = 0.0036; severe malaria OR = 1.6, P(Corr) = 0.02). The exon1 variants MBL2*B (severe malaria OR = 2.1, P(Corr) = 0.036; mild versus severe malaria OR = 2.5, P(Corr) = 0.039) and MBL2*C (mild versus severe malaria OR = 5.4, P(Corr) = 0.045) increased the odds of having malaria. The exon1 MBL2*D/*B/*C variant increased the risk for severe malaria (OR = 3.4, P(Corr) = 0.000045). The frequencies of low MBL haplotypes were significantly higher in severe malaria (14.2%) compared to mild malaria (7.9%) and asymptomatic (3.8%). The MBL2*LYPA haplotypes confer protection, whereas MBL2*LXPA increases the malaria risk. Our findings in Indian populations demonstrate that MBL2 functional variants are strongly associated with malaria and infection severity.",,"['Jha, Aditya Nath', 'Sundaravadivel, Pandarisamy', 'Singh, Vipin Kumar', 'Pati, Sudhanshu S.', 'Patra, Pradeep K.', 'Kremsner, Peter G.', 'Velavan, Thirumalaisamy P.', 'Singh, Lalji', 'Thangaraj, Kumarasamy']",,,,
,PMC,The role of trophoblastic microRNAs in placental viral infection,http://dx.doi.org/10.1387/ijdb.130349ys,PMC4377297,,,"During the past decade, various types of small non-coding RNAs were found to be expressed in all kingdoms and phyla of life. Intense research efforts have begun to shed light on their biological functions, although much remains to be determined in order to fully characterize their scope of biological action. Typically, small RNAs provide sequence specificity to a protein complex that is driven to silence a long target RNA. MicroRNAs (miRNAs) are small RNAs that are coded in the genome of most eukaryotes, and contribute to the cellular identity by regulating cell-specific gene networks by translational repression or degradation of mRNA. These effects commonly fine-tune gene expression associated with developmental or environmental cues. Different cell types can be characterized by their distinctive cellular miRNA landscape. The human placenta expresses a unique set of miRNAs, a high proportion of which is derived from a large cluster located on chromosome 19, (termed chromosome 19 miRNA cluster, or C19MC). Interestingly, a fraction of these placenta-enriched miRNAs are released to the extracellular environment through exosomes that were recently found to induce an antiviral immunity. In this review, we explore relevant placental viral infections and discuss the antiviral role of exosome-packaged placental C19MC miRNAs in this context.",,"['MOUILLET, JEAN-FRANCOIS', 'OUYANG, YINGSHI', 'BAYER, AVRAHAM', 'COYNE, CAROLYN B.', 'SADOVSKY, YOEL']",,,,
,PMC,Effect of Different Spectral Transmittances through Tinted Animal Cages on Circadian Metabolism and Physiology in Sprague–Dawley Rats,,PMC3894647,,,"The suprachiasmatic nucleus is synchronized by the light:dark cycle and is the master biologic clock that serves as a pacemaker to regulate circadian rhythms. We explored the hypothesis that spectral transmittance (tint) of light through caging alters circadian rhythms of endocrine and metabolic plasma constituents in nonpigmented Sprague–Dawley rats. Rats (Crl:SD; n = 12 per group) were housed in a 12:12-h light:dark environment (300 lx; 123.0 μW/cm(2); lights on, 0600) in either clear-, amber-, blue-, or red-tinted rodent cages. Blood was collected at 0400, 0800, 1200, 1600, 2000, and 2400 and measured for melatonin, total fatty acids, pH, glucose, lactic acid, corticosterone, insulin, and leptin. As expected, plasma melatonin levels were low during the light phase but higher during the dark phase in all groups; however, when compared with the clear-cage group, rats in amber-, blue-, and red-tinted cages had 29%, 74%, and 48%, respectively, greater total daily melatonin levels due to an increased duration and, in some cases, amplitude of the nocturnal melatonin signal. No differences were found in dietary and water intake, body growth rates, total fatty acids, pH, or glucose among groups. Disruptions in circadian rhythms, manifesting as alterations in phase timing, amplitude, or duration, occurred in the melatonin, lactic acid, corticosterone, insulin, and leptin levels of rats in tinted compared with clear cages. Therefore, the use of variously tinted animal cages significantly alters circadian rhythms in plasma measures of metabolism and physiology in laboratory rats, thus potentially altering the outcomes of scientific investigations.",,"['Wren, Melissa A', 'Dauchy, Robert T', 'Hanifin, John P', 'Jablonski, Michael R', 'Warfield, Benjamin', 'Brainard, George C', 'Blask, David E', 'Hill, Steven M', 'Ooms, Tara G', 'Bohm, Rudolf P']",,,,
,PMC,Evaluation of the BioFire FilmArray Respiratory Panel and the GenMark eSensor Respiratory Viral Panel on Lower Respiratory Tract Specimens,http://dx.doi.org/10.1128/JCM.02787-13,PMC3911424,,,We evaluated the performance characteristics of the FilmArray respiratory panel and the eSensor respiratory viral panel on clinical and spiked lower respiratory tract specimens (LRTS). The overall agreement between the two methods was 89.5% (51/57). The lower limit of detection of both assays for all targets in LRTS was comparable to that for nasopharyngeal swab specimens.,,"['Ruggiero, Phyllis', 'McMillen, Tracy', 'Tang, Yi-Wei', 'Babady, N. Esther']",,,,
,PMC,Real-Time Reverse Transcription-PCR Assay Panel for Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JCM.02533-13,PMC3911421,,,"A new human coronavirus (CoV), subsequently named Middle East respiratory syndrome (MERS)-CoV, was first reported in Saudi Arabia in September 2012. In response, we developed two real-time reverse transcription-PCR (rRT-PCR) assays targeting the MERS-CoV nucleocapsid (N) gene and evaluated these assays as a panel with a previously published assay targeting the region upstream of the MERS-CoV envelope gene (upE) for the detection and confirmation of MERS-CoV infection. All assays detected ≤10 copies/reaction of quantified RNA transcripts, with a linear dynamic range of 8 log units and 1.3 × 10(−3) 50% tissue culture infective doses (TCID(50))/ml of cultured MERS-CoV per reaction. All assays performed comparably with respiratory, serum, and stool specimens spiked with cultured virus. No false-positive amplifications were obtained with other human coronaviruses or common respiratory viral pathogens or with 336 diverse clinical specimens from non-MERS-CoV cases; specimens from two confirmed MERS-CoV cases were positive with all assay signatures. In June 2012, the U.S. Food and Drug Administration authorized emergency use of the rRT-PCR assay panel as an in vitro diagnostic test for MERS-CoV. A kit consisting of the three assay signatures and a positive control was assembled and distributed to public health laboratories in the United States and internationally to support MERS-CoV surveillance and public health responses.",,"['Lu, Xiaoyan', 'Whitaker, Brett', 'Sakthivel, Senthil Kumar K.', 'Kamili, Shifaq', 'Rose, Laura E.', 'Lowe, Luis', 'Mohareb, Emad', 'Elassal, Emad M.', 'Al-sanouri, Tarek', 'Haddadin, Aktham', 'Erdman, Dean D.']",,,,
,PMC,Isolation and Characterization of Porcine Epidemic Diarrhea Viruses Associated with the 2013 Disease Outbreak among Swine in the United States,http://dx.doi.org/10.1128/JCM.02820-13,PMC3911415,,,"Porcine epidemic diarrhea virus (PEDV) was detected in May 2013 for the first time in U.S. swine and has since caused significant economic loss. Obtaining a U.S. PEDV isolate that can grow efficiently in cell culture is critical for investigating pathogenesis and developing diagnostic assays and for vaccine development. An additional objective was to determine which gene(s) of PEDV is most suitable for studying the genetic relatedness of the virus. Here we describe two PEDV isolates (ISU13-19338E and ISU13-22038) successfully obtained from the small intestines of piglets from sow farms in Indiana and Iowa, respectively. The two isolates have been serially propagated in cell culture for over 30 passages and were characterized for the first 10 passages. Virus production in cell culture was confirmed by PEDV-specific real-time reverse-transcription PCR (RT-PCR), immunofluorescence assays, and electron microscopy. The infectious titers of the viruses during the first 10 passages ranged from 6 × 10(2) to 2 × 10(5) 50% tissue culture infective doses (TCID(50))/ml. In addition, the full-length genome sequences of six viruses (ISU13-19338E homogenate, P3, and P9; ISU13-22038 homogenate, P3, and P9) were determined. Genetically, the two PEDV isolates were relatively stable during the first 10 passages in cell culture. Sequences were also compared to those of 4 additional U.S. PEDV strains and 23 non-U.S. strains. All U.S. PEDV strains were genetically closely related to each other (≥99.7% nucleotide identity) and were most genetically similar to Chinese strains reported in 2011 to 2012. Phylogenetic analyses using different genes of PEDV suggested that the full-length spike gene or the S1 portion is appropriate for sequencing to study the genetic relatedness of these viruses.",,"['Chen, Qi', 'Li, Ganwu', 'Stasko, Judith', 'Thomas, Joseph T.', 'Stensland, Wendy R.', 'Pillatzki, Angela E.', 'Gauger, Phillip C.', 'Schwartz, Kent J.', 'Madson, Darin', 'Yoon, Kyoung-Jin', 'Stevenson, Gregory W.', 'Burrough, Eric R.', 'Harmon, Karen M.', 'Main, Rodger G.', 'Zhang, Jianqiang']",,,,
,PMC,Comparative analysis of disease pathogenesis and molecular mechanisms of New World and Old World arenavirus infections,http://dx.doi.org/10.1099/vir.0.057000-0,PMC4093776,,,"Arenaviruses can cause fatal human haemorrhagic fever (HF) diseases for which vaccines and therapies are extremely limited. Both the New World (NW) and Old World (OW) groups of arenaviruses contain HF-causing pathogens. Although these two groups share many similarities, important differences with regard to pathogenicity and molecular mechanisms of virus infection exist. These closely related pathogens share many characteristics, including genome structure, viral assembly, natural host selection and the ability to interfere with innate immune signalling. However, members of the NW and OW viruses appear to use different receptors for cellular entry, as well as different mechanisms of virus internalization. General differences in disease signs and symptoms and pathological lesions in patients infected with either NW or OW arenaviruses are also noted and discussed herein. Whilst both the OW Lassa virus (LASV) and the NW Junin virus (JUNV) can cause disruption of the vascular endothelium, which is an important pathological feature of HF, the immune responses to these related pathogens seem to be quite distinct. Whereas LASV infection results in an overall generalized immune suppression, patients infected with JUNV seem to develop a cytokine storm. Additionally, the type of immune response required for recovery and clearance of the virus is different between NW and OW infections. These differences may be important to allow the viruses to evade host immune detection. Understanding these differences will aid the development of new vaccines and treatment strategies against deadly HF viral infections.",,"['McLay, Lisa', 'Liang, Yuying', 'Ly, Hinh']",,,,
,PMC,How does breathing frequency affect the performance of an N95 filtering facepiece respirator and a surgical mask against surrogates of viral particles?,http://dx.doi.org/10.1080/15459624.2013.848037,PMC6768065,,,"BACKGROUND: Breathing frequency (breaths/min) differs among individuals and levels of physical activity. Particles enter respirators through two principle penetration pathways: faceseal leakage and filter penetration. However, it is unknown how breathing frequency affects the overall performance of N95 filtering facepiece respirators (FFRs) and surgical masks (SMs) against viral particles, as well as other health-relevant submicrometer particles. METHODS: A FFR and SM were tested on a breathing manikin at four mean inspiratory flows (MIFs) (15, 30, 55 and 85 L/min) and five breathing frequencies (10, 15, 20, 25 and 30 breaths/min). Filter penetration (P(filter)) and total inward leakage (TIL) were determined for the tested respiratory protection devices against sodium chloride (NaCl) aerosol particles in the size range of 20 to 500 nm. “Faceseal leakage-to-filter” (FLTF) penetration ratios were calculated. RESULTS: Both MIF and breathing frequency showed significant effects (p<0.05) on P(filter) and TIL. Increasing breathing frequency increased TIL for the N95 FFR whereas no clear trends were observed for the SM. Increasing MIF increased P(filter) and decreased TIL resulting in decreasing FLTF ratio. Most of FLTF ratios were >1, suggesting that the faceseal leakage was the primary particle penetration pathway at various breathing frequencies. CONCLUSIONS: Breathing frequency is another factor (besides MIF) that can significantly affect the performance of N95 FFRs, with higher breathing frequencies increasing TIL. No consistent trend of increase or decrease of TIL with either MIF or breathing frequency was observed for the tested SM. To potentially extend these findings beyond the manikin/breathing system used, future studies are needed to fully understand the mechanism causing the breathing frequency effect on the performance of respiratory protection devices on human subjects.",,"['He, Xinjian', 'Reponen, Tiina', 'McKay, Roy', 'Grinshpun, Sergey A.']",,,,
,PMC,Efficacy of Face Shields Against Cough Aerosol Droplets from a Cough Simulator,http://dx.doi.org/10.1080/15459624.2013.877591,PMC4734356,,,"Health care workers are exposed to potentially infectious airborne particles while providing routine care to coughing patients. However, much is not understood about the behavior of these aerosols and the risks they pose. We used a coughing patient simulator and a breathing worker simulator to investigate the exposure of health care workers to cough aerosol droplets, and to examine the efficacy of face shields in reducing this exposure. Our results showed that 0.9% of the initial burst of aerosol from a cough can be inhaled by a worker 46 cm (18 inches) from the patient. During testing of an influenza-laden cough aerosol with a volume median diameter (VMD) of 8.5 μm, wearing a face shield reduced the inhalational exposure of the worker by 96% in the period immediately after a cough. The face shield also reduced the surface contamination of a respirator by 97%. When a smaller cough aerosol was used (VMD = 3.4 μm), the face shield was less effective, blocking only 68% of the cough and 76% of the surface contamination. In the period from 1 to 30 minutes after a cough, during which the aerosol had dispersed throughout the room and larger particles had settled, the face shield reduced aerosol inhalation by only 23%. Increasing the distance between the patient and worker to 183 cm (72 inches) reduced the exposure to influenza that occurred immediately after a cough by 92%. Our results show that health care workers can inhale infectious airborne particles while treating a coughing patient. Face shields can substantially reduce the short-term exposure of health care workers to large infectious aerosol particles, but smaller particles can remain airborne longer and flow around the face shield more easily to be inhaled. Thus, face shields provide a useful adjunct to respiratory protection for workers caring for patients with respiratory infections. However, they cannot be used as a substitute for respiratory protection when it is needed.",,"['Lindsley, William G.', 'Noti, John D.', 'Blachere, Francoise M.', 'Szalajda, Jonathan V.', 'Beezhold, Donald H.']",,,,
,PMC,Commentary Considerations for Recommending Extended Use and Limited Reuse of Filtering Facepiece Respirators in Health Care Settings,http://dx.doi.org/10.1080/15459624.2014.902954,PMC4610368,,,"Public health organizations, such as the Centers for Disease Control and Prevention (CDC), are increasingly recommending the use of N95 filtering facepiece respirators (FFRs) in health care settings. For infection control purposes, the usual practice is to discard FFRs after close contact with a patient (“single use”). However, in some situations, such as during contact with tuberculosis patients, limited FFR reuse (i.e., repeated donning and doffing of the same FFR by the same person) is practiced. A related practice, extended use, involves wearing the same FFR for multiple patient encounters without doffing. Extended use and limited FFR reuse have been recommended during infectious disease outbreaks and pandemics to conserve FFR supplies. This commentary examines CDC recommendations related to FFR extended use and limited reuse and analyzes available data from the literature to provide a relative estimate of the risks of these practices compared to single use. Analysis of the available data and the use of disease transmission models indicate that decisions regarding whether FFR extended use or reuse should be recommended should continue to be pathogen- and event-specific. Factors to be included in developing the recommendations are the potential for the pathogen to spread via contact transmission, the potential that the event could result in or is currently causing a FFR shortage, the protection provided by FFR use, human factors, potential for self-inoculation, the potential for secondary exposures, and government policies and regulations. While recent findings largely support the previous recommendations for extended use and limited reuse in certain situations, some new cautions and limitations should be considered before issuing recommendations in the future. In general, extended use of FFRs is preferred over limited FFR reuse. Limited FFR reuse would allow the user a brief respite from extended wear times, but increases the risk of self-inoculation and preliminary data from one study suggest that some FFR models may begin to lose effectiveness after multiple donnings.",,"['Fisher, Edward M.', 'Shaffer, Ronald E.']",,,,
,PMC,A Quantitative Assessment of the Total Inward Leakage of NaCl Aerosol Representing Submicron-Size Bioaerosol Through N95 Filtering Facepiece Respirators and Surgical Masks,http://dx.doi.org/10.1080/15459624.2013.866715,PMC4589201,,,"Respiratory protection provided by a particulate respirator is a function of particle penetration through filter media and through faceseal leakage. Faceseal leakage largely contributes to the penetration of particles through a respirator and compromises protection. When faceseal leaks arise, filter penetration is assumed to be negligible. The contribution of filter penetration and faceseal leakage to total inward leakage (TIL) of submicron-size bioaerosols is not well studied. To address this issue, TIL values for two N95 filtering facepiece respirator (FFR) models and two surgical mask (SM) models sealed to a manikin were measured at 8 L and 40 L breathing minute volumes with different artificial leak sizes. TIL values for different size (20–800 nm, electrical mobility diameter) NaCl particles representing submicron-size bioaerosols were measured using a scanning mobility particle sizer. Efficiency of filtering devices was assessed by measuring the penetration against NaCl aerosol similar to the method used for NIOSH particulate filter certification. Results showed that the most penetrating particle size (MPPS) was ~45 nm for both N95 FFR models and one of the two SM models, and ~350 nm for the other SM model at sealed condition with no leaks as well as with different leak sizes. TIL values increased with increasing leak sizes and breathing minute volumes. Relatively, higher efficiency N95 and SM models showed lower TIL values. Filter efficiency of FFRs and SMs influenced the TIL at different flow rates and leak sizes. Overall, the data indicate that good fitting higher-efficiency FFRs may offer higher protection against submicron-size bioaerosols.",,"['Rengasamy, Samy', 'Eimer, Benjamin C.', 'Szalajda, Jonathan']",,,,
,PMC,Targeting the C-type Lectins-Mediated Host-Pathogen Interactions with Dextran,,PMC5553543,,,"Dextran, the α-1,6-linked glucose polymer widely used in biology and medicine, promises new applications. Linear dextran applied as a blood plasma substitute demonstrates a high rate of biocompatibility. Dextran is present in foods, drugs, and vaccines and in most cases is applied as a biologically inert substance. In this review we analyze dextran’s cellular uptake principles, receptor specificity and, therefore, its ability to interfere with pathogen–lectin interactions: a promising basis for new antimicrobial strategies. Dextran-binding receptors in humans include the DC-SIGN (dendritic cell–specific intercellular adhesion molecule 3-grabbing nonintegrin) family receptors: DC-SIGN (CD209) and L-SIGN (the liver and lymphatic endothelium homologue of DC-SIGN), the mannose receptor (CD206), and langerin. These receptors take part in the uptake of pathogens by dendritic cells and macrophages and may also participate in the modulation of immune responses, mostly shown to be beneficial for pathogens per se rather than host(s). It is logical to predict that owing to receptor-specific interactions, dextran or its derivatives can interfere with these immune responses and improve infection outcome. Recent data support this hypothesis. We consider dextran a promising molecule for the development of lectin–glycan interaction-blocking molecules (such as DC-SIGN inhibitors) that could be applied in the treatment of diseases including tuberculosis, influenza, hepatitis B and C, human immunodeficiency virus infection and AIDS, etc. Dextran derivatives indeed change the pathology of infections dependent on DC-SIGN and mannose receptors. Complete knowledge of specific dextran–lectin interactions may also be important for development of future dextran applications in biological research and medicine.",,"['Pustylnikov, Sergey', 'Sagar, Divya', 'Jain, Pooja', 'Khan, Zafar K.']",,,,
,PMC,Antiviral Natural Products and Herbal Medicines,http://dx.doi.org/10.4103/2225-4110.124335,PMC4032839,24872930,CC BY-NC-SA,"Viral infections play an important role in human diseases, and recent outbreaks in the advent of globalization and ease of travel have underscored their prevention as a critical issue in safeguarding public health. Despite the progress made in immunization and drug development, many viruses lack preventive vaccines and efficient antiviral therapies, which are often beset by the generation of viral escape mutants. Thus, identifying novel antiviral drugs is of critical importance and natural products are an excellent source for such discoveries. In this mini-review, we summarize the antiviral effects reported for several natural products and herbal medicines.",2014 Jan-Mar,"['Lin, Liang-Tzung', 'Hsu, Wen-Chan', 'Lin, Chun-Ching']",J Tradit Complement Med,,,
,PMC,Activation of Influenza A Viruses by Host Proteases from Swine Airway Epithelium,http://dx.doi.org/10.1128/JVI.01635-13,PMC3911738,,,"Pigs are important natural hosts of influenza A viruses, and due to their susceptibility to swine, avian, and human viruses, they may serve as intermediate hosts supporting adaptation and genetic reassortment. Cleavage of the influenza virus surface glycoprotein hemagglutinin (HA) by host cell proteases is essential for viral infectivity. Most influenza viruses, including human and swine viruses, are activated at a monobasic HA cleavage site, and we previously identified TMPRSS2 and HAT to be relevant proteases present in human airways. We investigated the proteolytic activation of influenza viruses in primary porcine tracheal and bronchial epithelial cells (PTEC and PBEC, respectively). Human H1N1 and H3N2 viruses replicated efficiently in PTECs and PBECs, and viruses containing cleaved HA were released from infected cells. Moreover, the cells supported the proteolytic activation of HA at the stage of entry. We found that swine proteases homologous to TMPRSS2 and HAT, designated swTMPRSS2 and swAT, respectively, were expressed in several parts of the porcine respiratory tract. Both proteases cloned from primary PBECs were shown to activate HA with a monobasic cleavage site upon coexpression and support multicycle replication of influenza viruses. swAT was predominantly localized at the plasma membrane, where it was present as an active protease that mediated activation of incoming virus. In contrast, swTMPRSS2 accumulated in the trans-Golgi network, suggesting that it cleaves HA in this compartment. In conclusion, our data show that HA activation in porcine airways may occur by similar proteases and at similar stages of the viral life cycle as in human airways.",,"['Peitsch, Catharina', 'Klenk, Hans-Dieter', 'Garten, Wolfgang', 'Böttcher-Friebertshäuser, Eva']",,,,
,PMC,Characterization of a Novel Betacoronavirus Related to Middle East Respiratory Syndrome Coronavirus in European Hedgehogs,http://dx.doi.org/10.1128/JVI.01600-13,PMC3911734,,,"Bats are known to host viruses closely related to important human coronaviruses (HCoVs), such as HCoV-229E, severe-acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome CoV (MERS-CoV). As RNA viruses may coevolve with their hosts, we sought to investigate the closest sister taxon to bats, the Eulipotyphla, and screened European hedgehogs (Erinaceus europaeus) from Germany for CoV by nested reverse transcriptase PCR. A novel betacoronavirus species in a phylogenetic sister relationship to MERS-CoV and clade c bat CoVs was detected and characterized on the whole-genome level. A total of 58.9% of hedgehog fecal specimens were positive for the novel CoV (EriCoV) at 7.9 log(10) mean RNA copies per ml. EriCoV RNA concentrations were higher in the intestine than in other solid organs, blood, or urine. Detailed analyses of the full hedgehog intestine showed the highest EriCoV concentrations in lower gastrointestinal tract specimens, compatible with viral replication in the lower intestine and fecal-oral transmission. Thirteen of 27 (48.2%) hedgehog sera contained non-neutralizing antibodies against MERS-CoV. The animal origins of this betacoronavirus clade that includes MERS-CoV may thus include both bat and nonbat hosts.",,"['Corman, Victor Max', 'Kallies, René', 'Philipps, Heike', 'Göpner, Gertraude', 'Müller, Marcel Alexander', 'Eckerle, Isabella', 'Brünink, Sebastian', 'Drosten, Christian', 'Drexler, Jan Felix']",,,,
,PMC,Human Coronavirus OC43 Nucleocapsid Protein Binds MicroRNA 9 and Potentiates NF-κB Activation,http://dx.doi.org/10.1128/JVI.02678-13,PMC3911702,,,"The human coronavirus OC43 is a major contributor to the common cold worldwide, though due to its low mortality rate, little research has focused on this human pathogen. The nucleocapsid is an essential structural protein with conserved functions across the coronavirus family. While a multitude of studies have examined nucleocapsid function, none have described the effects of OC43 nucleocapsid on the transcription factor NF-κB. We report that the nucleocapsid protein of OC43 causes potentiation of NF-κB activation. This prolonged activation is the direct result of the ability of the nucleocapsid to bind RNA, specifically microRNA 9 (miR-9), which is a negative regulator of NF-κB. This previously undescribed interaction between virus and host is a potential mechanism of immune evasion in RNA viruses.",,"['Lai, Frances W.', 'Stephenson, Kyle B.', 'Mahony, James', 'Lichty, Brian D.']",,,,
,PMC,A Lethal Disease Model for Hantavirus Pulmonary Syndrome in Immunosuppressed Syrian Hamsters Infected with Sin Nombre Virus,http://dx.doi.org/10.1128/JVI.02906-13,PMC3911685,,,"Sin Nombre virus (SNV) is a rodent-borne hantavirus that causes hantavirus pulmonary syndrome (HPS) predominantly in North America. SNV infection of immunocompetent hamsters results in an asymptomatic infection; the only lethal disease model for a pathogenic hantavirus is Andes virus (ANDV) infection of Syrian hamsters. Efforts to create a lethal SNV disease model in hamsters by repeatedly passaging virus through the hamster have demonstrated increased dissemination of the virus but no signs of disease. In this study, we demonstrate that immunosuppression of hamsters through the administration of a combination of dexamethasone and cyclophosphamide, followed by infection with SNV, results in a vascular leak syndrome that accurately mimics both HPS disease in humans and ANDV infection of hamsters. Immunosuppressed hamsters infected with SNV have a mean number of days to death of 13 and display clinical signs associated with HPS, including pulmonary edema. Viral antigen was widely detectable throughout the pulmonary endothelium. Histologic analysis of lung sections showed marked inflammation and edema within the alveolar septa of SNV-infected hamsters, results which are similar to what is exhibited by hamsters infected with ANDV. Importantly, SNV-specific neutralizing polyclonal antibody administered 5 days after SNV infection conferred significant protection against disease. This experiment not only demonstrated that the disease was caused by SNV, it also demonstrated the utility of this animal model for testing candidate medical countermeasures. This is the first report of lethal disease caused by SNV in an adult small-animal model.",,"['Brocato, Rebecca L.', 'Hammerbeck, Christopher D.', 'Bell, Todd M.', 'Wells, Jay B.', 'Queen, Laurie A.', 'Hooper, Jay W.']",,,,
,PMC,Ifit2 Deficiency Results in Uncontrolled Neurotropic Coronavirus Replication and Enhanced Encephalitis via Impaired Alpha/Beta Interferon Induction in Macrophages,http://dx.doi.org/10.1128/JVI.02272-13,PMC3911674,,,"Type I interferons (IFN-α/β) limit viral dissemination prior to the emergence of adaptive immune responses through the concerted action of interferon-stimulated genes (ISGs). Although IFN-α/β induction by coronaviruses is modest, it effectively limits viral spread within the central nervous system (CNS) and protects against mortality. The protective roles of specific ISGs against the mouse hepatitis virus (MHV) members of the coronaviruses are largely unknown. This study demonstrates a protective role of the ISG Ifit2 in encephalitis induced by the dual hepato- and neurotropic MHV-A59. Contrasting the mild encephalitis and 100% survival of MHV-A59-infected wild-type (wt) mice, nearly 60% of infected Ifit2(−/−) mice exhibited severe encephalitis and succumbed between 6 and 8 days postinfection. Increased clinical disease in Ifit2(−/−) mice coincided with higher viral loads and enhanced viral spread throughout the CNS parenchyma. Ifit2(−/−) mice also expressed significantly reduced IFN-α/β and downstream ISG mRNAs Ifit1, Isg15, and Pkr, while expression of proinflammatory cytokines and chemokines was only modestly affected in the CNS. Impaired IFN-α/β induction in the absence of Ifit2 was confirmed by ex vivo mRNA analysis of microglia and macrophages, the prominent cell types producing IFN-α/β following MHV CNS infection. Furthermore, both IFN-α/β mRNA and protein production were significantly reduced in MHV-infected Ifit2(−/−) relative to wt bone marrow-derived macrophages. Collectively, the data implicate Ifit2 as a positive regulator of IFN-α/β expression, rather than direct antiviral mediator, during MHV-induced encephalitis.",,"['Butchi, Niranjan B.', 'Hinton, David R.', 'Stohlman, Stephen A.', 'Kapil, Parul', 'Fensterl, Volker', 'Sen, Ganes C.', 'Bergmann, Cornelia C.']",,,,
,PMC,TMPRSS2 and ADAM17 Cleave ACE2 Differentially and Only Proteolysis by TMPRSS2 Augments Entry Driven by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein,http://dx.doi.org/10.1128/JVI.02202-13,PMC3911672,,,"The type II transmembrane serine proteases TMPRSS2 and HAT can cleave and activate the spike protein (S) of the severe acute respiratory syndrome coronavirus (SARS-CoV) for membrane fusion. In addition, these proteases cleave the viral receptor, the carboxypeptidase angiotensin-converting enzyme 2 (ACE2), and it was proposed that ACE2 cleavage augments viral infectivity. However, no mechanistic insights into this process were obtained and the relevance of ACE2 cleavage for SARS-CoV S protein (SARS-S) activation has not been determined. Here, we show that arginine and lysine residues within ACE2 amino acids 697 to 716 are essential for cleavage by TMPRSS2 and HAT and that ACE2 processing is required for augmentation of SARS-S-driven entry by these proteases. In contrast, ACE2 cleavage was dispensable for activation of the viral S protein. Expression of TMPRSS2 increased cellular uptake of soluble SARS-S, suggesting that protease-dependent augmentation of viral entry might be due to increased uptake of virions into target cells. Finally, TMPRSS2 was found to compete with the metalloprotease ADAM17 for ACE2 processing, but only cleavage by TMPRSS2 resulted in augmented SARS-S-driven entry. Collectively, our results in conjunction with those of previous studies indicate that TMPRSS2 and potentially related proteases promote SARS-CoV entry by two separate mechanisms: ACE2 cleavage, which might promote viral uptake, and SARS-S cleavage, which activates the S protein for membrane fusion. These observations have interesting implications for the development of novel therapeutics. In addition, they should spur efforts to determine whether receptor cleavage promotes entry of other coronaviruses, which use peptidases as entry receptors.",,"['Heurich, Adeline', 'Hofmann-Winkler, Heike', 'Gierer, Stefanie', 'Liepold, Thomas', 'Jahn, Olaf', 'Pöhlmann, Stefan']",,,,
,PMC,Quantitative Modeling of Virus Evolutionary Dynamics and Adaptation in Serial Passages Using Empirically Inferred Fitness Landscapes,http://dx.doi.org/10.1128/JVI.02958-13,PMC3911671,,,"We describe a stochastic virus evolution model representing genomic diversification and within-host selection during experimental serial passages under cell culture or live-host conditions. The model incorporates realistic descriptions of the virus genotypes in nucleotide and amino acid sequence spaces, as well as their diversification from error-prone replications. It quantitatively considers factors such as target cell number, bottleneck size, passage period, infection and cell death rates, and the replication rate of different genotypes, allowing for systematic examinations of how their changes affect the evolutionary dynamics of viruses during passages. The relative probability for a viral population to achieve adaptation under a new host environment, quantified by the rate with which a target sequence frequency rises above 50%, was found to be most sensitive to factors related to sequence structure (distance from the wild type to the target) and selection strength (host cell number and bottleneck size). For parameter values representative of RNA viruses, the likelihood of observing adaptations during passages became negligible as the required number of mutations rose above two amino acid sites. We modeled the specific adaptation process of influenza A H5N1 viruses in mammalian hosts by simulating the evolutionary dynamics of H5 strains under the fitness landscape inferred from multiple sequence alignments of H3 proteins. In light of comparisons with experimental findings, we observed that the evolutionary dynamics of adaptation is strongly affected not only by the tendency toward increasing fitness values but also by the accessibility of pathways between genotypes constrained by the genetic code.",,"['Woo, Hyung Jun', 'Reifman, Jaques']",,,,
,PMC,Discovery of a Novel Bottlenose Dolphin Coronavirus Reveals a Distinct Species of Marine Mammal Coronavirus in Gammacoronavirus,http://dx.doi.org/10.1128/JVI.02351-13,PMC3911666,,,"While gammacoronaviruses mainly comprise infectious bronchitis virus (IBV) and its closely related bird coronaviruses (CoVs), the only mammalian gammacoronavirus was discovered from a white beluga whale (beluga whale CoV [BWCoV] SW1) in 2008. In this study, we discovered a novel gammacoronavirus from fecal samples from three Indo-Pacific bottlenose dolphins (Tursiops aduncus), which we named bottlenose dolphin CoV (BdCoV) HKU22. All the three BdCoV HKU22-positive samples were collected on the same date, suggesting a cluster of infection, with viral loads of 1 × 10(3) to 1 × 10(5) copies per ml. Clearance of virus was associated with a specific antibody response against the nucleocapsid of BdCoV HKU22. Complete genome sequencing and comparative genome analysis showed that BdCoV HKU22 and BWCoV SW1 have similar genome characteristics and structures. Their genome size is about 32,000 nucleotides, the largest among all CoVs, as a result of multiple unique open reading frames (NS5a, NS5b, NS5c, NS6, NS7, NS8, NS9, and NS10) between their membrane (M) and nucleocapsid (N) protein genes. Although comparative genome analysis showed that BdCoV HKU22 and BWCoV SW1 should belong to the same species, a major difference was observed in the proteins encoded by their spike (S) genes, which showed only 74.3 to 74.7% amino acid identities. The high ratios of the number of synonymous substitutions per synonymous site (K(s)) to the number of nonsynonymous substitutions per nonsynonymous site (K(a)) in multiple regions of the genome, especially the S gene (K(a)/K(s) ratio, 2.5), indicated that BdCoV HKU22 may be evolving rapidly, supporting a recent transmission event to the bottlenose dolphins. We propose a distinct species, Cetacean coronavirus, in Gammacoronavirus, to include BdCoV HKU22 and BWCoV SW1, whereas IBV and its closely related bird CoVs represent another species, Avian coronavirus, in Gammacoronavirus.",,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Lam, Carol S. F.', 'Tsang, Alan K. L.', 'Hui, Suk-Wai', 'Fan, Rachel Y. Y.', 'Martelli, Paolo', 'Yuen, Kwok-Yung']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.03467-13,PMC3911657,,,,,,,,,
,PMC,A Targeted Mutation within the Feline Leukemia Virus (FeLV) Envelope Protein Immunosuppressive Domain To Improve a Canarypox Virus-Vectored FeLV Vaccine,http://dx.doi.org/10.1128/JVI.02234-13,PMC3911645,,,"We previously delineated a highly conserved immunosuppressive (IS) domain within murine and primate retroviral envelope proteins that is critical for virus propagation in vivo. The envelope-mediated immunosuppression was assessed by the ability of the proteins, when expressed by allogeneic tumor cells normally rejected by engrafted mice, to allow these cells to escape, at least transiently, immune rejection. Using this approach, we identified key residues whose mutation (i) specifically abolishes immunosuppressive activity without affecting the “mechanical” function of the envelope protein and (ii) significantly enhances humoral and cellular immune responses elicited against the virus. The objective of this work was to study the immunosuppressive activity of the envelope protein (p15E) of feline leukemia virus (FeLV) and evaluate the effect of its abolition on the efficacy of a vaccine against FeLV. Here we demonstrate that the FeLV envelope protein is immunosuppressive in vivo and that this immunosuppressive activity can be “switched off” by targeted mutation of a specific amino acid. As a result of the introduction of the mutated envelope sequence into a previously well characterized canarypox virus-vectored vaccine (ALVAC-FeLV), the frequency of vaccine-induced FeLV-specific gamma interferon (IFN-γ)-producing cells was increased, whereas conversely, the frequency of vaccine-induced FeLV-specific interleukin-10 (IL-10)-producing cells was reduced. This shift in the IFN-γ/IL-10 response was associated with a higher efficacy of ALVAC-FeLV against FeLV infection. This study demonstrates that FeLV p15E is immunosuppressive in vivo, that the immunosuppressive domain of p15E can modulate the FeLV-specific immune response, and that the efficacy of FeLV vaccines can be enhanced by inhibiting the immunosuppressive activity of the IS domain through an appropriate mutation.",,"['Schlecht-Louf, Géraldine', 'Mangeney, Marianne', 'El-Garch, Hanane', 'Lacombe, Valérie', 'Poulet, Hervé', 'Heidmann, Thierry']",,,,
,PMC,Inhibition of NF-κB-Mediated Inflammation in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice Increases Survival,http://dx.doi.org/10.1128/JVI.02576-13,PMC3911641,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of a respiratory disease that has a 10% mortality rate. We previously showed that SARS-CoV lacking the E gene (SARS-CoV-ΔE) is attenuated in several animal model systems. Here, we show that absence of the E protein resulted in reduced expression of proinflammatory cytokines, decreased numbers of neutrophils in lung infiltrates, diminished lung pathology, and increased mouse survival, suggesting that lung inflammation contributed to SARS-CoV virulence. Further, infection with SARS-CoV-ΔE resulted in decreased activation of NF-κB compared to levels for the wild-type virus. Most important, treatment with drugs that inhibited NF-κB activation led to a reduction in inflammation and lung pathology in both SARS-CoV-infected cultured cells and mice and significantly increased mouse survival after SARS-CoV infection. These data indicated that activation of the NF-κB signaling pathway represents a major contribution to the inflammation induced after SARS-CoV infection and that NF-κB inhibitors are promising antivirals in infections caused by SARS-CoV and potentially other pathogenic human coronaviruses.",,"['DeDiego, Marta L.', 'Nieto-Torres, Jose L.', 'Regla-Nava, Jose A.', 'Jimenez-Guardeño, Jose M.', 'Fernandez-Delgado, Raul', 'Fett, Craig', 'Castaño-Rodriguez, Carlos', 'Perlman, Stanley', 'Enjuanes, Luis']",,,,
,PMC,Signaling Pathways in Murine Dendritic Cells That Regulate the Response to Vesicular Stomatitis Virus Vectors That Express Flagellin,http://dx.doi.org/10.1128/JVI.02898-13,PMC3911629,,,"Vesicular stomatitis virus (VSV) vectors that express heterologous antigens have shown promise as vaccines in preclinical studies. The efficacy of VSV-based vaccines can be improved by engineering vectors that enhance innate immune responses. We previously generated a VSV vaccine vector that incorporates two enhancing strategies: an M protein mutation (M51R) that prevents the virus from suppressing host antiviral responses and a gene encoding bacterial flagellin (M51R-F vector). The rationale was that intracellular expression of flagellin would activate innate immune pathways in addition to those activated by virus alone. This was tested with dendritic cells (DCs) from mice containing deletions in key signaling molecules. Infection of DC with either M51R or M51R-F vector induced the production of interleukin-12 (IL-12) and IL-6 and increased surface expression of T cell costimulatory molecules. These responses were dramatically reduced in DCs from IPS-1(−/−) mice. Infection with M51R-F vector also induced the production of IL-1β. In addition, in approximately half of the DCs, M51R-F vector induced pyroptosis, a proinflammatory-type of cell death. These responses to flagellin were ablated in DCs from NLRC4(−/−) mice but not Toll-like receptor 5-deficient (TLR5(−/−)) mice, indicating that they resulted from inflammasome activation. These results demonstrate that flagellin induces additional innate immune mechanisms over those induced by VSV alone.",,"['Smedberg, Jason R.', 'Westcott, Marlena M.', 'Ahmed, Maryam', 'Lyles, Douglas S.']",,,,
,PMC,Reselection of a Genomic Upstream Open Reading Frame in Mouse Hepatitis Coronavirus 5′-Untranslated-Region Mutants,http://dx.doi.org/10.1128/JVI.02831-13,PMC3911626,,,"An AUG-initiated upstream open reading frame (uORF) encoding a potential polypeptide of 3 to 13 amino acids (aa) is found within the 5′ untranslated region (UTR) of >75% of coronavirus genomes based on 38 reference strains. Potential CUG-initiated uORFs are also found in many strains. The AUG-initiated uORF is presumably translated following genomic 5′-end cap-dependent ribosomal scanning, but its function is unknown. Here, in a reverse-genetics study with mouse hepatitis coronavirus, the following were observed. (i) When the uORF AUG-initiating codon was replaced with a UAG stop codon along with a U112A mutation to maintain a uORF-harboring stem-loop 4 structure, an unimpaired virus with wild-type (WT) growth kinetics was recovered. However, reversion was found at all mutated sites within five virus passages. (ii) When the uORF was fused with genomic (main) ORF1 by converting three in-frame stop codons to nonstop codons, a uORF-ORF1 fusion protein was made, and virus replicated at WT levels. However, a frameshifting G insertion at virus passage 7 established a slightly 5′-extended original uORF. (iii) When uAUG-eliminating deletions of 20, 30, or 51 nucleotides (nt) were made within stem-loop 4, viable but debilitated virus was recovered. However, a C80U mutation in the first mutant and an A77G mutation in the second appeared by passage 10, which generated alternate uORFs that correlated with restored WT growth kinetics. In vitro, the uORF-disrupting nondeletion mutants showed enhanced translation of the downstream ORF1 compared with the WT. These results together suggest that the uORF represses ORF1 translation yet plays a beneficial but nonessential role in coronavirus replication in cell culture.",,"['Wu, Hung-Yi', 'Guan, Bo-Jhih', 'Su, Yu-Pin', 'Fan, Yi-Hsin', 'Brian, David A.']",,,,
,PMC,Emerging infectious diseases,http://dx.doi.org/10.1016/j.mpmed.2013.10.014,PMC3929004,24563608,NO-CC CODE,"The spectrum of human pathogens and the infectious diseases they cause is continuously changing through evolution and changes in the way human populations interact with their environment and each other. New human pathogens most often emerge from an animal reservoir, emphasizing the central role that non-human reservoirs play in human infectious diseases. Pathogens may also re-emerge with new characteristics, such as multidrug-resistance, or in different places, such as West Nile virus in the USA in 1999, to cause new epidemics. Most human pathogens have a history of evolution in which they first emerge and cause epidemics, become unstably adapted, re-emerge periodically, and eventually become endemic with the potential for future outbreaks.",2014 Jan,"van Doorn, H. Rogier",Medicine (Abingdon),,,
,PMC,Serum Profiling Using Protein Microarrays to Identify Disease Related Antigens,http://dx.doi.org/10.1007/978-1-4939-0992-6_14,PMC4420618,,,"Disease related antigens are of great importance in the clinic. They are used as markers to screen patients for various forms of cancer, to monitor response to therapy, or to serve as therapeutic targets (Chapman et al., Ann Oncol 18(5):868–873, 2007; Soussi et al., Cancer Res 60:1777–1788, 2000; Anderson and LaBaer, J Proteome Res 4:1123–1133, 2005; Levenson, Biochim Biophy Acta 1770:847–856, 2007). In cancer endogenous levels of protein expression may be disrupted or proteins may be expressed in an aberrant fashion resulting in an immune response that bypasses self tolerance (Soussi et al., Cancer Res 60:1777–1788, 2000; Disis et al., J Clin Oncol 15(11):3363–3367, 1997; Molina et al., Breast Cancer Res Treat 51:109–119, 1998). Protein microarrays, which represent a large fraction of the human proteome, have been used to identify antigens in multiple diseases including cancer (Anderson and LaBaer, J Proteome Res 4:1123–1133, 2005; Disis et al., J Clin Oncol 15(11):3363–3367, 1997; Hudson et al., Proc Natl Acad Sci U S A 104(44):17494–17499, 2007; Beyer et al., J Neuroimmunol 242:26–32, 2012). Typically, arrays are probed with immunoglobulin (Ig) samples from patients as well as healthy controls, then compared to determine which antigens (Ag's) are more reactive within the patient group (Hudson et al., Proc Natl Acad Sci U S A 104(44):17494–17499).",,"['Sharon, Donald', 'Snyder, Michael']",,,,
,PMC,Virus-like particles as antigenic nanomaterials for inducing protective immune responses in the lung,http://dx.doi.org/10.2217/nnm.14.107,PMC4415509,,,"The lung is a major entry point for many of the most detrimental pathogens to human health. The onslaught of pathogens encountered by the lung is counteracted by protective immune responses that are generated locally, which can be stimulated through vaccine strategies to prevent pathogen infections. Here, we discuss the use of virus-like particles (VLPs), nonpathogen derivatives of viruses or protein cage structures, to construct new vaccines exploiting the lung as a site for immunostimulation. VLPs are unique in their ability to be engineered with near molecular level detail and knowledge of their composition and structure. A summary of research in developing VLP-based vaccines for the lung is presented that suggests promising results for future vaccine development.",,"['Rynda-Apple, Agnieszka', 'Patterson, Dustin P', 'Douglas, Trevor']",,,,
,PMC,A current update on the phytopharmacological aspects of Houttuynia cordata Thunb,http://dx.doi.org/10.4103/0973-7847.125525,PMC3931198,24600193,CC BY-NC-SA,"The present review is an attempt to put an insight into a medicinal plant Houttuynia cordata Thunb, which is indigenous to North-East India and China. It is an aromatic medicinal herb belonging to family Saururaceae and is restricted to specialized moist habitats. The review provides detailed information regarding the morphology, distribution, phytochemistry, ethnopharmacological uses and also describes various pharmacological activities reported on the plant H. cordata. The review describes therapeutic efficacy of the whole plant and its extracts, fractions and isolated compounds in different diseased condition. Among the important pharmacological activities reported includes, anti-mutagenic, anti-cancer, adjuvanticity, anti-obesity, hepatoprotective, anti-viral, anti-bacterial, anti-inflammatory, free radical scavenging, anti-microbial, anti-allergic, anti-leukemic, chronic sinusitis and nasal polyps activities. Thus, the present review will act as a source of referential information to researchers to perform clinical studies on isolated compounds that may serve the society and will help in improving human health care system.",2014 Jan-Jun,"['Kumar, Manish', 'Prasad, Satyendra K.', 'Hemalatha, S.']",Pharmacogn Rev,,,
,PMC,International Union of Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors,http://dx.doi.org/10.1124/pr.113.007724,PMC3880466,,,"Sixteen years ago, the Nomenclature Committee of the International Union of Pharmacology approved a system for naming human seven-transmembrane (7TM) G protein-coupled chemokine receptors, the large family of leukocyte chemoattractant receptors that regulates immune system development and function, in large part by mediating leukocyte trafficking. This was announced in Pharmacological Reviews in a major overview of the first decade of research in this field [Murphy PM, Baggiolini M, Charo IF, Hébert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ, and Power CA (2000) Pharmacol Rev 52:145–176]. Since then, several new receptors have been discovered, and major advances have been made for the others in many areas, including structural biology, signal transduction mechanisms, biology, and pharmacology. New and diverse roles have been identified in infection, immunity, inflammation, development, cancer, and other areas. The first two drugs acting at chemokine receptors have been approved by the U.S. Food and Drug Administration (FDA), maraviroc targeting CCR5 in human immunodeficiency virus (HIV)/AIDS, and plerixafor targeting CXCR4 for stem cell mobilization for transplantation in cancer, and other candidates are now undergoing pivotal clinical trials for diverse disease indications. In addition, a subfamily of atypical chemokine receptors has emerged that may signal through arrestins instead of G proteins to act as chemokine scavengers, and many microbial and invertebrate G protein-coupled chemokine receptors and soluble chemokine-binding proteins have been described. Here, we review this extended family of chemokine receptors and chemokine-binding proteins at the basic, translational, and clinical levels, including an update on drug development. We also introduce a new nomenclature for atypical chemokine receptors with the stem ACKR (atypical chemokine receptor) approved by the Nomenclature Committee of the International Union of Pharmacology and the Human Genome Nomenclature Committee.",,"['Bachelerie, Francoise', 'Ben-Baruch, Adit', 'Burkhardt, Amanda M.', 'Combadiere, Christophe', 'Farber, Joshua M.', 'Graham, Gerard J.', 'Horuk, Richard', 'Sparre-Ulrich, Alexander Hovard', 'Locati, Massimo', 'Luster, Andrew D.', 'Mantovani, Alberto', 'Matsushima, Kouji', 'Murphy, Philip M.', 'Nibbs, Robert', 'Nomiyama, Hisayuki', 'Power, Christine A.', 'Proudfoot, Amanda E. I.', 'Rosenkilde, Mette M.', 'Rot, Antal', 'Sozzani, Silvano', 'Thelen, Marcus', 'Yoshie, Osamu', 'Zlotnik, Albert']",,,,
,PMC,Facts and ideas from anywhere,,PMC3862139,,,,,,,,,
,PMC,Acronyms List,,PMC4187321,,,,,,,,,
,PMC,Health-Care Provider Preferences for Time-Sensitive Communications from Public Health Agencies,,PMC4187309,,,"OBJECTIVE: The Rapid Emergency Alert Communication in Health (REACH) Trial was a randomized control trial to systematically compare and evaluate the effectiveness of traditional and mobile communication modalities for public health agencies to disseminate time-sensitive information to health-care providers (HCPs). We conducted a sub-study to identify the communication channels by which HCPs preferred receiving public health alerts and advisories. METHODS: Enrolled HCPs were blindly randomized into four message delivery groups to receive time-sensitive public health messages by e-mail, fax, or short message service (SMS) or to a no-message control group. Follow-up interviews were conducted 5–10 days after the message. In the final interview, additional questions were asked regarding HCP preferences for receiving public health alerts and advisories. We examined the relationship between key covariates and preferred method of receiving public health alert and advisory messages. RESULTS: Gender, age, provider type, and study site showed statistically significant associations with delivery method preference. Older providers were more likely than younger providers to prefer e-mail or fax, while younger providers were more likely than older providers to prefer receiving messages via SMS. CONCLUSIONS: There is currently no evidence-based research to guide or improve communication between public health agencies and HCPs. Understanding the preferences of providers for receiving alerts and advisories may improve the effectiveness of vital public health communications systems and, in turn, may enhance disease surveillance, aid in early detection, and improve case finding and situational awareness for public health emergencies.",,"['Revere, Debra', 'Painter, Ian', 'Oberle, Mark', 'Baseman, Janet G.']",,,,
,PMC,"Enhancing the Work of the Department of Health and Human Services National Vaccine Program in Global Immunization: Recommendations of the National Vaccine Advisory Committee: Approved by the National Vaccine Advisory Committee on September 12, 2013",,PMC4121882,,,,,,,,,
,PMC,PROPHYLACTIC ANTIBODY TREATMENT AND INTRAMUSCULAR IMMUNIZATION REDUCE INFECTIOUS HUMAN RHINOVIRUS 16 LOAD IN THE LOWER RESPIRATORY TRACT OF CHALLENGED COTTON RATS,http://dx.doi.org/10.1016/j.trivac.2014.02.003,PMC4199241,,,"Human rhinoviruses (HRV) represent the single most important etiological agents of the common cold and are the most frequent cause of acute respiratory infections in humans. Currently the performance of available animal models for immunization studies using HRV challenge is very limited. The cotton rat (Sigmodon hispidus) is a well-recognized model for the study of human respiratory viral infections. In this work we show that, without requiring any genetic modification of either the host or the virus, intranasal infection of cotton rats with HRV16 resulted in measurable lower respiratory tract pathology, mucus production, and expression of interferon-activated genes. Intramuscular immunization with live HRV16 generated robust protective immunity that correlated with high serum levels of neutralizing antibodies. In addition, cotton rats treated prophylactically with hyperimmune anti-HRV16 serum were protected against HRV16 intranasal challenge. Finally, protection by immunization was efficiently transferred from mothers to newborn animals resulting in a substantial reduction of infectious virus loads in the lung following intranasal challenge. Overall, our results demonstrate that the cotton rat provides valuable additional model development options for testing vaccines and prophylactic therapies against rhinovirus infection.",,"['Blanco, Jorge C. G.', 'Core, Susan', 'Pletneva, Lioubov M.', 'March, Thomas H.', 'Boukhvalova, Marina S.', 'Kajon, Adriana E.']",,,,
,PMC,Humans and Cattle: A Review of Bovine Zoonoses,http://dx.doi.org/10.1089/vbz.2012.1164,PMC3880910,,,"Infectious disease prevention and control has been among the top public health objectives during the last century. However, controlling disease due to pathogens that move between animals and humans has been challenging. Such zoonotic pathogens have been responsible for the majority of new human disease threats and a number of recent international epidemics. Currently, our surveillance systems often lack the ability to monitor the human–animal interface for emergent pathogens. Identifying and ultimately addressing emergent cross-species infections will require a “One Health” approach in which resources from public veterinary, environmental, and human health function as part of an integrative system. Here we review the epidemiology of bovine zoonoses from a public health perspective.",,"['McDaniel, Clinton J.', 'Cardwell, Diana M.', 'Moeller, Robert B.', 'Gray, Gregory C.']",,,,
,PMC,Presepsin as a novel sepsis biomarker,http://dx.doi.org/10.5847/wjem.j.issn.1920-8642.2014.01.002,PMC4129857,,,"BACKGROUND: In 2004, a new biomarker sCD14-subtypes (presepsin) was found and its value was shown in the diagnosis and evaluation of sepsis. This article is a brief overview of the new biomarker. DATA SOURCES: A literature search using multiple databases was performed for articles, especially meta-analyses, systematic reviews, and randomized controlled trials. RESULTS: Compared with other markers, presepsin seems to have a better sensitivity and specificity in the diagnosis of sepsis. Presepsin as a biom1arker is not only suitable for the early diagnosis of sepsis, but also for the assessment of its severity and prognosis. CONCLUSIONS: Presepsin has a higher sensitivity and specificity in the diagnosis of sepsis as a new biomarker, and is a predictor for the prognosis of sepsis. More importantly, preseptin seems to play a crucial role as a supplemental method in the early diagnosis of sepsis. Since there is no multicenter study on the relationship between presepsin and sepsis, further studies on the clinical values of presepsin are needed.",,"['Zou, Qi', 'Wen, Wei', 'Zhang, Xin-chao']",,,,
,PMC,Genomic Sequences of a Low Passage Herpes Simplex Virus 2 Clinical Isolate and its Plaque-purified Derivative Strain,http://dx.doi.org/10.1016/j.virol.2013.12.014,PMC3955984,,,"Herpes simplex virus 2 is an important human pathogen as the causative agent of genital herpes, neonatal herpes, and increased risk of HIV acquisition and transmission. Nevertheless, the only genomic sequence that has been completed is the attenuated HSV-2 HG52 laboratory strain. In this study we defined the genomic sequence of the HSV-2 SD90e low passage clinical isolate and a plaque-purified derivative, SD90-3P. We found minimal sequence differences between SD90e and SD90-3P. However, in comparisons with the HSV-2 HG52 reference genome sequence, the SD90e genome ORFs contained numerous point mutations, 13 insertions/delections (indels), and 9 short compensatory frameshifts. The indels were true sequence differences, but the compensatory frameshifts were likely sequence errors in the original HG52 sequence. Because HG52 virus is less virulent than other HSV-2 strains and may not be representative of wildtype HSV-2 strains, we propose that the HSV-2 SD90e genome serve as the new HSV-2 reference genome.",,"['Colgrove, Robert', 'Diaz, Fernando', 'Newman, Ruchi', 'Saif, Sakina', 'Shea, Terry', 'Young, Sarah', 'Henn, Matt', 'Knipe, David M.']",,,,
,PMC,Yeast-expressed recombinant protein of the receptor-binding domain in SARS-CoV spike protein with deglycosylated forms as a SARS vaccine candidate,http://dx.doi.org/10.4161/hv.27464,PMC4130269,,,"Development of vaccines for preventing a future pandemic of severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV) and for biodefense preparedness is urgently needed. Our previous studies have shown that a candidate SARS vaccine antigen consisting of the receptor-binding domain (RBD) of SARS-CoV spike protein can induce potent neutralizing antibody responses and protection against SARS-CoV challenge in vaccinated animals. To optimize expression conditions for scale-up production of the RBD vaccine candidate, we hypothesized that this could be potentially achieved by removing glycosylation sites in the RBD protein. In this study, we constructed two RBD protein variants: 1) RBD193-WT (193-aa, residues 318–510) and its deglycosylated forms (RBD193-N1, RBD193-N2, RBD193-N3); 2) RBD219-WT (219-aa, residues 318–536) and its deglycosylated forms (RBD219-N1, RBD219-N2, and RBD219-N3). All constructs were expressed as recombinant proteins in yeast. The purified recombinant proteins of these constructs were compared for their antigenicity, functionality and immunogenicity in mice using alum as the adjuvant. We found that RBD219-N1 exhibited high expression yield, and maintained its antigenicity and functionality. More importantly, RBD219-N1 induced significantly stronger RBD-specific antibody responses and a higher level of neutralizing antibodies in immunized mice than RBD193-WT, RBD193-N1, RBD193-N3, or RBD219-WT. These results suggest that RBD219-N1 could be selected as an optimal SARS vaccine candidate for further development.",,"['Chen, Wen-Hsiang', 'Du, Lanying', 'Chag, Shivali M', 'Ma, Cuiqing', 'Tricoche, Nancy', 'Tao, Xinrong', 'Seid, Christopher A', 'Hudspeth, Elissa M', 'Lustigman, Sara', 'Tseng, Chien-Te K', 'Bottazzi, Maria Elena', 'Hotez, Peter J', 'Zhan, Bin', 'Jiang, Shibo']",,,,
,PMC,Plasminogen activator inhibitor-1 in sputum and nasal fluids increases in asthmatics during common colds,http://dx.doi.org/10.1016/j.jaci.2013.11.009,PMC4004714,,,This study showed that sputum and nasal lavage levels of plasminogen activator inhibitor-1 (PAI-1) rise during a common cold in asthmatic patients. This rise may contribute to the progression of airway remodeling.,,"['Cho, Seong H.', 'Hong, Seung J.', 'Chen, Haimei', 'Habib, Ali', 'Cho, David', 'Lee, Sun H.', 'Kang, Joseph', 'Ward, Theresa', 'Boushey, Homer A.', 'Schleimer, Robert P.', 'Avila, Pedro C.']",,,,
,PMC,Respiratory Syncytial Virus in Hematopoietic Cell Transplant Recipients: Factors Determining Progression to Lower Respiratory Tract Disease,http://dx.doi.org/10.1093/infdis/jit832,PMC3969549,,,"Background. Respiratory syncytial virus (RSV) lower respiratory tract disease (LRD) is a life-threatening complication in hematopoietic cell transplant (HCT) recipients. Lymphopenia has been associated with an increased risk of progression from upper respiratory tract infection (URI) to LRD. Methods. This study retrospectively analyzed the significance of lymphocyte engraftment dynamics, lung function, smoking history, corticosteroids, antiviral treatment, viral subtypes, and RSV-specific neutralizing antibodies for the progression to LRD in 181 HCT recipients with RSV URI. Results. In multivariable models, smoking history, conditioning with high-dose total body irradiation, and an absolute lymphocyte count (ALC) ≤100/mm(3) at the time of URI onset were significantly associated with disease progression. No progression occurred in patients with ALCs of >1000/mm(3) at URI onset. Lymphocyte engraftment dynamics were similar in progressors and nonprogressors. Pre- and posttransplant donor and posttransplant recipient RSV subtype-specific neutralizing antibody levels, RSV viral subtypes, and corticosteroids also were not significantly associated with LRD progression. Conclusions. Host and transplant related factors appear to determine the risk of progression to LRD more than viral factors. Dysfunctional cell-mediated immunity appears to be important in the pathogenesis of progressive RSV disease after HCT. A characterization of RSV-specific T-cell immunity is warranted.",,"['Kim, Yae-Jean', 'Guthrie, Katherine A.', 'Waghmare, Alpana', 'Walsh, Edward E.', 'Falsey, Ann R.', 'Kuypers, Jane', 'Cent, Anne', 'Englund, Janet A.', 'Boeckh, Michael']",,,,
,PMC,Early hypercytokinemia is associated with interferon-induced transmembrane protein-3 dysfunction and predictive of fatal H7N9 infection,http://dx.doi.org/10.1073/pnas.1321748111,PMC3896201,,,"A unique avian-origin A/H7N9 influenza virus has so far caused 134 cases with 44 deaths. Probing the host factors contributing to disease severity, we found that lower levels of plasma inflammatory cytokines on hospital admission correlated with faster recovery in 18 patients with A/H7N9 influenza virus, whereas high concentrations of (in particular) IL-6, IL-8, and macrophage inflammatory protein-1β were predictive of a less favorable or fatal outcome. Analysis of bronchoalveolar lavage samples showed up to 1,000-fold greater cytokine/chemokine levels relative to plasma. Furthermore, patients with the rs12252-C/C IFN-induced transmembrane protein-3 (IFITM3) genotype had more rapid disease progression and were less likely to survive. Compared with patients with the rs12252-T/T or rs12252-T/C genotype of IFITM3, patients with the C/C genotype had a shorter time from disease onset to the time point when they sought medical aid (hospital admission or antiviral therapy) and a shorter interval to development of the acute respiratory distress syndrome stage (reflected by shorter intervals between clinical onset and methylprednisolone treatments and higher rates of mechanical ventilator use), as well as experiencing elevated/prolonged lung virus titers and cytokine production and higher mortality. The present analysis provides reported data on the H7N9 influenza-induced “cytokine storm” at the site of infection in humans and identifies the rs12252-C genotype that compromises IFITM3 function as a primary genetic correlate of severe H7N9 pneumonia. Together with rs12252 sequencing, early monitoring of plasma cytokines is thus of prognostic value for the treatment and management of severe influenza pneumonia.",,"['Wang, Zhongfang', 'Zhang, Anli', 'Wan, Yanmin', 'Liu, Xinian', 'Qiu, Chao', 'Xi, Xiuhong', 'Ren, Yanqin', 'Wang, Jing', 'Dong, Yuan', 'Bao, Meijuan', 'Li, Liangzhu', 'Zhou, Mingzhe', 'Yuan, Songhua', 'Sun, Jun', 'Zhu, Zhaoqin', 'Chen, Liang', 'Li, Qingsheng', 'Zhang, Zhiyong', 'Zhang, Xiaoyan', 'Lu, Shuihua', 'Doherty, Peter C.', 'Kedzierska, Katherine', 'Xu, Jianqing']",,,,
,PMC,MERS-CoV papain-like protease has deISGylating and deubiquitinating activities,http://dx.doi.org/10.1016/j.virol.2013.11.040,PMC3957432,,,"Coronaviruses encode papain-like proteases (PLpro) that are often multifunctional enzymes with protease activity to process the viral replicase polyprotein and deubiquitinating (DUB)/deISGylating activity, which is hypothesized to modify the innate immune response to infection. Here, we investigate the predicted DUB activity of the PLpro domain of the recently described Middle East Respiratory Syndrome Coronavirus (MERS-CoV). We found that expression of MERS-CoV PLpro reduces the levels of ubiquitinated and ISGylated host cell proteins; consistent with multifunctional PLpro activity. Further, we compared the ability of MERS-CoV PLpro and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) PLpro to block innate immune signaling of proinflammatory cytokines. We show that expression of SARS-CoV and MERS-CoV PLpros blocks upregulation of cytokines CCL5, IFN-β and CXCL10 in stimulated cells. Overall these results indicate that the PLpro domains of MERS-CoV and SARS-CoV have the potential to modify the innate immune response to viral infection and contribute to viral pathogenesis.",,"['Mielech, Anna M.', 'Kilianski, Andy', 'Baez-Santos, Yahira M.', 'Mesecar, Andrew D.', 'Baker, Susan C.']",,,,
,PMC,Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities,http://dx.doi.org/10.1089/ars.2012.5068,PMC3869544,,,"The pathophysiology of multiple sclerosis (MS) involves several components: redox, inflammatory/autoimmune, vascular, and neurodegenerative. All of them are supported by the intertwined lines of evidence, and none of them should be written off. However, the exact mechanisms of MS initiation, its development, and progression are still elusive, despite the impressive pace by which the data on MS are accumulating. In this review, we will try to integrate the current facts and concepts, focusing on the role of redox changes and various reactive species in MS. Knowing the schedule of initial changes in pathogenic factors and the key turning points, as well as understanding the redox processes involved in MS pathogenesis is the way to enable MS prevention, early treatment, and the development of therapies that target specific pathophysiological components of the heterogeneous mechanisms of MS, which could alleviate the symptoms and hopefully stop MS. Pertinent to this, we will outline (i) redox processes involved in MS initiation; (ii) the role of reactive species in inflammation; (iii) prooxidative changes responsible for neurodegeneration; and (iv) the potential of antioxidative therapy. Antioxid. Redox Signal. 19, 2286–2334.",,"['Miljković, Djordje', 'Spasojević, Ivan']",,,,
,PMC,Evidence for a crucial role of a host non-coding RNA in influenza A virus replication,http://dx.doi.org/10.4161/rna.27504,PMC3929426,,,"A growing body of evidence suggests the non-protein coding human genome is of vital importance for human cell function. Besides small RNAs, the diverse class of long non-coding RNAs (lncRNAs) recently came into focus. However, their relevance for infection, a major evolutionary driving force, remains elusive. Using two commercially available microarray systems, namely NCode™ and Sureprint™ G3, we identified differential expression of 42 ncRNAs during influenza A virus (IAV) infection in human lung epithelial cells. This included several classes of lncRNAs, including large intergenic ncRNAs (lincRNAs). As analyzed by qRT-PCR, expression of one lincRNA, which we termed virus inducible lincRNA (VIN), is induced by several IAV strains (H1N1, H3N2, H7N7) as well as vesicular stomatitis virus. However, we did not observe an induction of VIN by influenza B virus, treatment with RNA mimics, or IFNβ. Thus, VIN expression seems to be a specific response to certain viral infections. RNA fractionation and RNA-FISH experiments revealed that VIN is localized to the host cell nucleus. Most importantly, we show that abolition of VIN by RNA interference restricts IAV replication and viral protein synthesis, highlighting the relevance of this lincRNA for productive IAV infection. Our observations suggest that viral pathogens interfere with the non-coding portion of the human genome, thereby guaranteeing their successful propagation, and that the expression of VIN correlates with their virulence. Consequently, our study provides a novel approach for understanding virus pathogenesis in greater detail, which will enable future design of new antiviral strategies targeting the host’s non-protein coding genome.",,"['Winterling, Carla', 'Koch, Manuel', 'Koeppel, Max', 'Garcia-Alcalde, Fernando', 'Karlas, Alexander', 'Meyer, Thomas F']",,,,
,PMC,STAT2 and IRF9: Beyond ISGF3,http://dx.doi.org/10.4161/jkst.27521,PMC3906322,,,"Cytokine signaling is mediated by the combinatorial usage of seven STAT proteins that form homo- or heterodimers involved in the regulation of specific transcriptional programs. Among STATs, STAT2 is classically known to dimerize with STAT1 and together with IRF9 forms the ISGF3 transcription factor complex that has long been considered a hallmark of activation by type I and type III interferons. However, accumulating evidence reveal distinct facets of STAT2 and IRF9 activity mediated by the segregation in alternative STAT1-independent complexes/pathways that are thought to trigger different transcriptional programs. The goal of this review is to summarize our current knowledge of the stimuli, regulatory mechanisms, and function of these alternative pathways.",,"['Fink, Karin', 'Grandvaux, Nathalie']",,,,
,PMC,Chitosan Nanoparticle Encapsulated Hemagglutinin-Split Influenza Virus Mucosal Vaccine,http://dx.doi.org/10.1208/s12249-013-0058-7,PMC3969489,,,"Subunit/split influenza vaccines are less reactogenic compared with the whole virus vaccines. However, their immunogenicity is relatively low and thus required proper adjuvant and/or delivery vehicle for immunogenicity enhancement. Influenza vaccines administered intramuscularly induce minimum, if any, mucosal immunity at the respiratory mucosa which is the prime site of the infection. In this study, chitosan (CS) nanoparticles were prepared by ionic cross-linking of the CS with sodium tripolyphosphate (TPP) at the CS/TPP ratio of 1:0.6 using 2 h mixing time. The CS/TPP nanoparticles were used as delivery vehicle of an intranasal influenza vaccine made of hemagglutinin (HA)-split influenza virus product. Innocuousness, immunogenicity, and protective efficacy of the CS/TPP-HA vaccine were tested in influenza mouse model in comparison with the antigen alone vaccine. The CS/TPP-HA nanoparticles had required characteristics including nano-sizes, positive charges, and high antigen encapsulation efficiency. Mice that received two doses of the CS/TPP-HA vaccine intranasally showed no adverse symptoms indicating the vaccine innocuousness. The animals developed higher systemic and mucosal antibody responses than vaccine made of the HA-split influenza virus alone. The CS/TPP-HA vaccine could induce also a cell-mediated immune response shown as high numbers of IFN-γ-secreting cells in spleens while the HA vaccine alone could not. Besides, the CS nanoparticle encapsulated HA-split vaccine reduced markedly the influenza morbidity and also conferred 100% protective rate to the vaccinated mice against lethal influenza virus challenge. Overall results indicated that the CS nanoparticles invented in this study is an effective and safe delivery vehicle/adjuvant for the influenza vaccine.",,"['Sawaengsak, Chompoonuch', 'Mori, Yasuko', 'Yamanishi, Koichi', 'Mitrevej, Ampol', 'Sinchaipanid, Nuttanan']",,,,
,PMC,Host genome polymorphisms and tuberculosis infection: What we have to say?,http://dx.doi.org/10.1016/j.ejcdt.2013.12.002,PMC4782973,,,"Several epidemiology studies suggest that host genetic factors play important roles in susceptibility, protection and progression of tuberculosis infection. Here we have reviewed the implications of some genetic polymorphisms in pathways related to tuberculosis susceptibility, severity and development. Large case-control studies examining single-nucleotide polymorphisms (SNPs) in genes have been performed in tuberculosis patients in some countries. Polymorphisms in natural resistance-associated macrophage protein 1 (NRAMP1), toll-like receptor 2 (TLR2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-1 receptor antagonist (IL-1RA), IL-10, vitamin D receptor (VDR), dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN), monocyte chemoattractant protein-1 (MCP-1), nucleotide oligomerization binding domain 2 (NOD2), interferon-gamma (IFN-γ), inducible nitric oxide synthase (iNOS), mannose-binding lectin (MBL) and surfactant proteins A (SP-A) have been reviewed. These genes have been variably associated with tuberculosis infection and there is strong evidence indicating that host genetic factors play critical roles in tuberculosis susceptibility, severity and development.",,"['Khalilullah, Said Alfin', 'Harapan, Harapan', 'Hasan, Nabeeh A.', 'Winardi, Wira', 'Ichsan, Ichsan', 'Mulyadi, Mulyadi']",,,,
,PMC,Early response to the emergence of influenza A(H7N9) virus in humans in China: the central role of prompt information sharing and public communication,http://dx.doi.org/10.2471/BLT.13.125989,PMC3967572,,,"PROBLEM: In 2003, China’s handling of the early stages of the epidemic of severe acute respiratory syndrome (SARS) was heavily criticized and generally considered to be suboptimal. APPROACH: Following the SARS outbreak, China made huge investments to improve surveillance, emergency preparedness and response capacity and strengthen public health institutions. In 2013, the return on these investments was evaluated by investigating China’s early response to the emergence of avian influenza A(H7N9) virus in humans. LOCAL SETTING: Clusters of human infection with a novel influenza virus were detected in China – by national surveillance of pneumonia of unknown etiology – on 26 February 2013. RELEVANT CHANGES: On 31 March 2013, China notified the World Health Organization (WHO) of the first recorded human infections with A(H7N9) virus. Poultry markets – which were rapidly identified as a major source of transmission of A(H7N9) to humans – were closed down in the affected areas. Surveillance in humans and poultry was heightened and technical guidelines were quickly updated and disseminated. The health authorities collaborated with WHO in risk assessments and risk communication. New cases were reported promptly and publicly. LESSONS LEARNT: The relevant infrastructures, surveillance systems and response capacity need to be strengthened in preparation for future emergencies caused by emerging or existing disease threats. Results of risk assessments and other data should be released promptly and publicly and such release should not jeopardize future publication of the data in scientific journals. Coordination between public health and veterinary services would be stronger during an emergency if these services had already undertaken joint preparedness planning.",,"['Vong, Sirenda', 'O’Leary, Michael', 'Feng, Zijian']",,,,
,PMC,The Francisella O-antigen mediates survival in the macrophage cytosol via autophagy avoidance,http://dx.doi.org/10.1111/cmi.12246,PMC4028363,,,"Autophagy is a key innate immune response to intracellular parasites that promotes their delivery to degradative lysosomes following detection in the cytosol or within damaged vacuoles. Like Listeria and Shigella, which use specific mechanisms to avoid autophagic detection and capture, the bacterial pathogen Francisella tularensis proliferates within the cytosol of macrophages without demonstrable control by autophagy. To examine how Francisella evades autophagy, we screened a library of F. tularensis subsp. tularensis Schu S4 HimarFT transposon mutants in GFP-LC3-expressing murine macrophages by microscopy for clones localised within autophagic vacuoles after phagosomal escape. Eleven clones showed autophagic capture at six hours post-infection, whose HimarFT insertions clustered to four genetic loci involved in lipopolysaccharidic and capsular O-antigen biosynthesis. Consistent with the HimarFT mutants, in-frame deletion mutants of two representative loci, FTT1236 and FTT1448c (manC), lacking both LPS and capsular O-antigen, underwent phagosomal escape but were cleared from the host cytosol. Unlike wild type Francisella, the O-antigen deletion mutants were ubiquitinated, and recruited the autophagy adaptor p62/SQSTM1 and LC3 prior to cytosolic clearance. Autophagy-deficient macrophages partially supported replication of both mutants, indicating that O-antigen-lacking Francisella are controlled by autophagy. These data demonstrate the intracellular protective role of this bacterial surface polysaccharide against autophagy.",,"['Di Russo Case, Elizabeth', 'Chong, Audrey', 'Wehrly, Tara D.', 'Hansen, Bryan', 'Child, Robert', 'Hwang, Seungmin', 'Virgin, Herbert W.', 'Celli, Jean']",,,,
,PMC,Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study,http://dx.doi.org/10.1016/S0140-6736(13)61887-5,PMC3898949,24055451,NO-CC CODE,"BACKGROUND: Since June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has, worldwide, caused 104 infections in people including 49 deaths, with 82 cases and 41 deaths reported from Saudi Arabia. In addition to confirming diagnosis, we generated the MERS-CoV genomic sequences obtained directly from patient samples to provide important information on MERS-CoV transmission, evolution, and origin. METHODS: Full genome deep sequencing was done on nucleic acid extracted directly from PCR-confirmed clinical samples. Viral genomes were obtained from 21 MERS cases of which 13 had 100%, four 85–95%, and four 30–50% genome coverage. Phylogenetic analysis of the 21 sequences, combined with nine published MERS-CoV genomes, was done. FINDINGS: Three distinct MERS-CoV genotypes were identified in Riyadh. Phylogeographic analyses suggest the MERS-CoV zoonotic reservoir is geographically disperse. Selection analysis of the MERS-CoV genomes reveals the expected accumulation of genetic diversity including changes in the S protein. The genetic diversity in the Al-Hasa cluster suggests that the hospital outbreak might have had more than one virus introduction. INTERPRETATION: We present the largest number of MERS-CoV genomes (21) described so far. MERS-CoV full genome sequences provide greater detail in tracking transmission. Multiple introductions of MERS-CoV are identified and suggest lower R(0) values. Transmission within Saudi Arabia is consistent with either movement of an animal reservoir, animal products, or movement of infected people. Further definition of the exposures responsible for the sporadic introductions of MERS-CoV into human populations is urgently needed. FUNDING: Saudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre.",2013 Dec 14,"['Cotten, Matthew', 'Watson, Simon J', 'Kellam, Paul', 'Al-Rabeeah, Abdullah A', 'Makhdoom, Hatem Q', 'Assiri, Abdullah', 'Al-Tawfiq, Jaffar A', 'Alhakeem, Rafat F', 'Madani, Hossam', 'AlRabiah, Fahad A', 'Hajjar, Sami Al', 'Al-nassir, Wafa N', 'Albarrak, Ali', 'Flemban, Hesham', 'Balkhy, Hanan H', 'Alsubaie, Sarah', 'Palser, Anne L', 'Gall, Astrid', 'Bashford-Rogers, Rachael', 'Rambaut, Andrew', 'Zumla, Alimuddin I', 'Memish, Ziad A']",Lancet,,,
,PMC,An update on A(H7N9) and MERS-CoV: Advice to health care professionals during influenza season: NOTES FROM THE DEPUTY CHIEF PUBLIC HEALTH OFFICER,http://dx.doi.org/10.14745/ccdr.v39i02a01,PMC6798730,,,,,,,,,
,PMC,"Viruses Associated With Acute Respiratory Infections and Influenza-like Illness Among Outpatients From the Influenza Incidence Surveillance Project, 2010–2011",http://dx.doi.org/10.1093/infdis/jit806,PMC5749912,,,"BACKGROUND: The Influenza Incidence Surveillance Project (IISP) monitored outpatient acute respiratory infection (ARI; defined as the presence of ≥2 respiratory symptoms not meeting ILI criteria) and influenza-like illness (ILI) to determine the incidence and contribution of associated viral etiologies. METHODS: From August 2010 through July 2011, 57 outpatient healthcare providers in 12 US sites reported weekly the number of visits for ILI and ARI and collected respiratory specimens on a subset for viral testing. The incidence was estimated using the number of patients in the practice as the denominator, and the virus-specific incidence of clinic visits was extrapolated from the proportion of patients testing positive. RESULTS: The age-adjusted cumulative incidence of outpatient visits for ARI and ILI combined was 95/1000 persons, with a viral etiology identified in 58% of specimens. Most frequently detected were rhinoviruses/enteroviruses (RV/EV) (21%) and influenza viruses (21%); the resulting extrapolated incidence of outpatient visits was 20 and 19/1000 persons respectively. The incidence of influenza virus-associated clinic visits was highest among patients aged 2–17 years, whereas other viruses had varied patterns among age groups. CONCLUSIONS: The IISP provides a unique opportunity to estimate the outpatient respiratory illness burden by etiology. Influenza virus infection and RV/EV infection(s) represent a substantial burden of respiratory disease in the US outpatient setting, particularly among children.",,"['Fowlkes, Ashley', 'Giorgi, Andrea', 'Erdman, Dean', 'Temte, Jon', 'Goodin, Kate', 'Di Lonardo, Steve', 'Sun, Yumei', 'Martin, Karen', 'Feist, Michelle', 'Linz, Rachel', 'Boulton, Rachelle', 'Bancroft, Elizabeth', 'McHugh, Lisa', 'Lojo, Jose', 'Filbert, Kimberly', 'Finelli, Lyn', None]",,,,
,PMC,"Structural Characterization of the glycoprotein GP2 Core Domain from the CAS Virus, a Novel Arenavirus-like Species",http://dx.doi.org/10.1016/j.jmb.2013.12.009,PMC3951589,,,"Fusion of the viral and host cell membranes is a necessary first step for infection by enveloped viruses, and is mediated by the envelope glycoprotein. The transmembrane subunits from the structurally defined “class I” glycoproteins adopt an α-helical “trimer- of-hairpins” conformation during the fusion pathway. Here we present our studies on the envelope glycoprotein transmembrane subunit, GP2, of the CAS virus (CASV). CASV was recently identified from annulated tree boas (Corallus annulatus) with inclusion body disease and is implicated in the disease etiology. We have generated and characterized two protein constructs consisting of the predicted CASV GP2 core domain. The crystal structure of the CASV GP2 post-fusion conformation indicates a trimeric α-helical bundle that is highly similar to those of Ebola Virus (EBOV) and Marburg Virus (MARV) GP2, despite CASV genome homology to arenaviruses. Denaturation studies demonstrate that the stability of CASV GP2 is pH-dependent with higher stability at lower pH; we propose that this behavior is due to a network of interactions among acidic residues that would destabilize the α-helical bundle under conditions where the side chains are deprotonated. The pH-dependent stability of the post-fusion structure has been observed in EBOV and MARV GP2, as well as other viruses that enter via the endosome. Infection experiments with CASV and the related Golden Gate Virus (GGV) support a mechanism of entry that requires endosomal acidification. Our results suggest that despite being primarily arenavirus-like, the transmembrane subunit of CASV is extremely similar to the filoviruses.",,"['Koellhoffer, Jayne F.', 'Dai, Zhou', 'Malashkevich, Vladimir N.', 'Stenglein, Mark D.', 'Liu, Yanyun', 'Toro, Rafael', 'Harrison, Joseph', 'Chandran, Kartik', 'DeRisi, Joseph L.', 'Almo, Steven C.', 'Lai, Jonathan R.']",,,,
,PMC,Reverse Transcription Recombinase Polymerase Amplification Assay for the Detection of Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1371/currents.outbreaks.62df1c7c75ffc96cd59034531e2e8364,PMC3871419,24459611,CC BY,"The emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the eastern Mediterranean and imported cases to Europe has alerted public health authorities. Currently, detection of MERS-CoV in patient samples is done by real-time RT-PCR. Samples collected from suspected cases are sent to highly-equipped centralized laboratories for screening. A rapid point-of-care test is needed to allow more widespread mobile detection of the virus directly from patient material. In this study, we describe the development of a reverse transcription isothermal Recombinase Polymerase Amplification (RT-RPA) assay for the identification of MERS-CoV. A partial nucleocapsid gene RNA molecular standard of MERS-coronavirus was used to determine the assay sensitivity. The isothermal (42°C) MERS-CoV RT-RPA was as sensitive as real-time RT-PCR (10 RNA molecules), rapid (3-7 minutes) and mobile (using tubescanner weighing 1kg). The MERS-CoV RT-RPA showed cross-detection neither of any of the RNAs of several coronaviruses and respiratory viruses affecting humans nor of the human genome. The developed isothermal real-time RT-RPA is ideal for rapid mobile molecular MERS-CoV monitoring in acute patients and may also facilitate the search for the animal reservoir of MERS-CoV.",2013 Dec 12,"['Abd El Wahed, Ahmed', 'Patel, Pranav', 'Heidenreich, Doris', 'Hufert, Frank T.', 'Weidmann, Manfred']",PLoS Curr,,,
,PMC,T cell mediated suppression of neurotropic coronavirus replication in neural precursor cells,http://dx.doi.org/10.1016/j.virol.2013.11.025,PMC3894587,,,"Neural precursor cells (NPCs) are the subject of intense investigation for their potential to treat neurodegenerative disorders, yet the consequences of neuroinvasive virus infection of NPCs remain unclear. This study demonstrates that NPCs support replication following infection by the neurotropic JHM strain of mouse hepatitis virus (JHMV). JHMV infection leads to increased cell death and dampens IFN-γ-induced MHC class II expression. Importantly, cytokines secreted by CD4+ T cells inhibit JHMV replication in NPCs, and CD8+ T cells specifically target viral peptide-pulsed NPCs for lysis. Furthermore, treatment with IFN-γ inhibits JHMV replication in a dose-dependent manner. Together, these findings suggest that T cells play a critical role in controlling replication of a neurotropic virus in NPCs, a finding which has important implications when considering immune modulation for NPC-based therapies for treatment of human neurologic diseases.",,"['Plaisted, Warren C.', 'Weinger, Jason G.', 'Walsh, Craig M.', 'Lane, Thomas E.']",,,,
,PMC,Molecular detection and genetic characterization of kobuviruses and astroviruses in asymptomatic local pigs in East Africa,http://dx.doi.org/10.1007/s00705-013-1942-x,PMC4094370,,,"In this study, swine fecal specimens (n = 251) collected from nursing and weaned piglets raised under smallholder production systems were screened for the presence of kobuviruses by RT-PCR. Porcine kobuviruses were detected in 13.1 % (33/251) of the samples. We demonstrated that porcine kobuvirus infections exist in indigenous pigs in Kenya and Uganda and that the prevalence was higher in young piglets than older pigs: nursing piglets (15 %), post-weaning (3-month-old) pigs (17 %), 4-month-old pigs (10 %). Genetic analysis of the partial RNA-dependent RNA polymerase (RdRp) region (690 nt) revealed that kobuviruses circulating in East Africa are diverse, sharing nucleotide sequence identities ranging from 89.7 to 99.1 % and 88 to 92.3 % among them and with known porcine kobuviruses, respectively. The nucleotide sequence identities between our kobuvirus strains and those of human, bovine and canine kobuviruses were 69.4-70.7 %, 73.1-74.4 % and 67-70.7 %, respectively. Additionally, upon sequencing selected samples that showed consistent 720-bp RT-PCR bands while using the same primer set, we detected porcine astroviruses in our samples belonging to type 2 and type 3 mamastroviruses. To our knowledge, this study reports the first detection and molecular analysis of both porcine kobuviruses and astroviruses in an African region. Further studies are required to determine the role of these viruses in gastrointestinal infections of pigs in this region and to determine the genetic diversity of the circulating strains to develop accurate diagnostic tools and implement appropriate control strategies.",,"['Amimo, Joshua O.', 'Okoth, Edward', 'Junga, Joseph O.', 'Ogara, William O.', 'Njahira, Moses N.', 'Wang, Qiuhong', 'Vlasova, Anastasia N.', 'Saif, Linda J.', 'Djikeng, Appolinaire']",,,,
,PMC,Electronic recording and reporting system for tuberculosis in China: experience and opportunities,http://dx.doi.org/10.1136/amiajnl-2013-002001,PMC4147602,,,"Tuberculosis (TB) surveillance in China is organized through a nationwide network of about 3200 hospitals and health facilities. In 2005, an electronic Tuberculosis Information Management System (TBIMS) started to be phased in to replace paper recording. The TBIMS collects key information on TB cases notified in TB care facilities, and exchanges real-time data with the Infectious Disease Reporting System, which covers the country’s 37 notifiable diseases. The system is accessible to authorized users at every level of the TB network through a password-protected website. By 2009 the TBIMS achieved nationwide coverage. Completeness of data on patient bacteriological end points improved remarkably over time. Data on about a million active TB cases, including drug-resistant TB, are included each year. The sheer scale of the data handling and the intricate functions that the China TBIMS performs makes it stand apart from the electronic information systems for TB adopted in other countries.",,"['Huang, Fei', 'Cheng, ShiMing', 'Du, Xin', 'Chen, Wei', 'Scano, Fabio', 'Falzon, Dennis', 'Wang, Lixia']",,,,
,PMC,"Middle East respiratory syndrome coronavirus not detected in children hospitalized with acute respiratory illness in Amman, Jordan, March 2010 to September 2012",http://dx.doi.org/10.1111/1469-0691.12438,PMC4618562,,,"Hospitalized children < 2 years of age in Amman, Jordan, admitted for fever and/or respiratory symptoms, were tested for Middle East respiratory syndrome coronavirus (MERS-CoV): MERS-CoV by real-time RT-PCR (rRT-PCR). This was a prospective year-round viral surveillance study in children <2 years of age admitted with acute respiratory symptoms and/or fever from March 2010 to September 2012 and enrolled from a government-run hospital, Al-Bashir in Amman, Jordan. Clinical and demographic data, including antibiotic use, were collected. Combined nasal/throat swabs were collected, aliquoted, and frozen at −80°C. Specimen aliquots were shipped to Vanderbilt University and the Centers for Disease Control and Prevention (CDC), and tested by rRT-PCR for MERS-CoV. Of the 2433 subjects enrolled from 16 March 2010 to 10 September 2012, 2427 subjects had viral testing and clinical data. Of 1898 specimens prospectively tested for other viruses between 16 March 2010 and 18 March 2012, 474 samples did not have other common respiratory viruses detected. These samples were tested at CDC for MERS-CoV and all were negative by rRT-PCR for MERS-CoV. Of the remaining 531 samples, collected from 19 March 2012 to 10 September 2012 and tested at Vanderbilt, none were positive for MERS-CoV. Our negative findings from a large sample of young Jordanian children hospitalized with fever and/or respiratory symptoms suggest that MERS-CoV was not widely circulating in Amman, Jordan, during the 30-month period of prospective, active surveillance occurring before and after the first documented MERS-CoV outbreak in the Middle East region.",,"['Khuri-Bulos, N.', 'Payne, D. C.', 'Lu, X.', 'Erdman, D.', 'Wang, L.', 'Faouri, S.', 'Shehabi, A.', 'Johnson, M.', 'Becker, M. M.', 'Denison, M. R.', 'Williams, J. V.', 'Halasa, N. B.']",,,,
,PMC,"The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists",http://dx.doi.org/10.1007/s13238-013-3096-8,PMC4875403,,,"The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic respiratory virus with pathogenic mechanisms that may be driven by innate immune pathways. The goal of this study is to characterize the expression of the structural (S, E, M, N) and accessory (ORF 3, ORF 4a, ORF 4b, ORF 5) proteins of MERS-CoV and to determine whether any of these proteins acts as an interferon antagonist. Individual structural and accessory protein-coding plasmids with an N-terminal HA tag were constructed and transiently transfected into cells, and their native expression and subcellular localization were assessed using Wes tern blotting and indirect immunofluorescence. While ORF 4b demonstrated majorly nuclear localization, all of the other proteins demonstrated cytoplasmic localization. In addition, for the first time, our experiments revealed that the M, ORF 4a, ORF 4b, and ORF 5 proteins are potent interferon antagonists. Further examination revealed that the ORF 4a protein of MERS-CoV has the most potential to counteract the antiviral effects of IFN via the inhibition of both the interferon production (IFN-β promoter activity, IRF-3/7 and NF-κB activation) and ISRE promoter element signaling pathways. Together, our results provide new insights into the function and pathogenic role of the structural and accessory proteins of MERS-CoV.",,"['Yang, Yang', 'Zhang, Ling', 'Geng, Heyuan', 'Deng, Yao', 'Huang, Baoying', 'Guo, Yin', 'Zhao, Zhengdong', 'Tan, Wenjie']",,,,
,PMC,Serotype-Specific Host Responses in Rhesus Macaques after Primary Dengue Challenge,http://dx.doi.org/10.4269/ajtmh.13-0145,PMC3854881,,,"Dengue virus (DENV) is considered to be the most important arthropod-borne viral disease and causes more than 100 million human infections annually. To further characterize primary DENV infection in vivo, rhesus macaques were infected with DENV-1, DENV-2, DENV-3, or DENV-4 and clinical parameters, as well as specificity and longevity of serologic responses, were assessed. Overt clinical symptoms were not present after infection. However, abnormalities in blood biochemical parameters consistent with heart, kidney, and liver damage were observed, and changes in plasma fibrinogen, D-dimers, and protein C indicated systemic activation of the blood coagulation pathway. Significant homotypic and heterotypic serum immunoglobulins were present in all animals, and IgG persisted for at least 390 days. Serum neutralizing antibody responses were highly serotype specific by day 120. However, some heterotypic neutralizing activity was noted in infected animals. Identification of serotype-specific host responses may help elucidate mechanisms that mediate severe DENV disease after reinfection.",,"['Hickey, Andrew C.', 'Koster, Jacob A.', 'Thalmann, Claudia M.', 'Hardcastle, Kathy', 'Tio, Phaik-Hooi', 'Cardosa, Mary J.', 'Bossart, Katharine N.']",,,,
,PMC,Recent progress in adjuvant discovery for peptide-based subunit vaccines,http://dx.doi.org/10.4161/hv.27332,PMC4130256,,,"Peptide-based subunit vaccines are of great interest in modern immunotherapy as they are safe, easy to produce and well defined. However, peptide antigens produce a relatively weak immune response, and thus require the use of immunostimulants (adjuvants) for optimal efficacy. Developing a safe and effective adjuvant remains a challenge for peptide-based vaccine design. Recent advances in immunology have allowed researchers to have a better understanding of the immunological implication of related diseases, which facilitates more rational design of adjuvant systems. Understanding the molecular structure of the adjuvants allows the establishment of their structure-activity relationships which is useful for the development of next-generation adjuvants. This review summarizes the current state of adjuvants development in the field of synthetic peptide-based vaccines. The structural, chemical and biological properties of adjuvants associated with their immunomodulatory effects are discussed.",,"['Azmi, Fazren', 'Ahmad Fuaad, Abdullah Al Hadi', 'Skwarczynski, Mariusz', 'Toth, Istvan']",,,,
,PMC,Toll-like receptors in antiviral innate immunity,http://dx.doi.org/10.1016/j.jmb.2013.11.024,PMC3943763,,,"Toll-like receptors (TLRs) are fundamental sensor molecules of the host innate immune system, which detect conserved molecular signatures of a wide range of microbial pathogens and initiate innate immune responses via distinct signaling pathways. Various TLRs are implicated in the early interplay of host cells with invading viruses, which regulates viral replication and/or host responses, ultimately impacting on viral pathogenesis. To survive the host innate defense mechanisms, many viruses have developed strategies to evade or counteract signaling through the TLR pathways, creating an advantageous environment for their propagation. Here we review the current knowledge of the roles TLRs play in antiviral innate immune responses, discuss examples of TLR-mediated viral recognition, and describe strategies used by viruses to antagonize the host antiviral innate immune responses.",,"['Lester, Sandra N.', 'Li, Kui']",,,,
,PMC,"WHO Framework Convention on Tobacco Control in China: Barriers, Challenges and Recommendations",http://dx.doi.org/10.1177/1757975913501910,PMC4041682,,,,,"Hu, Teh-Wei",,,,
,PMC,Viral Subversion of Nucleocytoplasmic Trafficking,http://dx.doi.org/10.1111/tra.12137,PMC3910510,,,"Trafficking of proteins and RNA into and out of the nucleus occurs through the nuclear pore complex (NPC). Due to its critical function in many cellular processes, the NPC and transport factors are common targets of several viruses that disrupt key constituents of the machinery to facilitate viral replication. Many viruses such as poliovirus and severe acute respiratory syndrome (SARS) virus inhibit protein import into the nucleus, while viruses such as influenza A virus target and disrupt host mRNA nuclear export. Current evidence indicates that these viruses may employ such strategies to avert the host immune response. Conversely, many viruses co-opt nucleocytoplasmic trafficking to facilitate transport of viral RNAs. Since viral proteins interact with key regulators of the host nuclear transport machinery, viruses have served as invaluable tools of discovery that led to the identification of novel constituents of nuclear transport pathways. In addition, this review explores the importance of nucleocytoplasmic trafficking to viral pathogenesis as these studies revealed new antiviral therapeutic strategies and exposed previously unknown cellular mechanisms. Further understanding of nuclear transport pathways will determine whether such therapeutics will be useful treatments for important human pathogens.",,"['Yarbrough, Melanie L.', 'Mata, Miguel A.', 'Sakthivel, Ramanavelan', 'Fontoura, Beatriz M. A.']",,,,
,PMC,Knowledge and attitudes of infection prevention and control among health sciences students at University of Namibia,http://dx.doi.org/10.4314/ahs.v13i4.30,PMC4056508,,,"BACKGROUND: Health Sciences students are exposed early to hospitals and to activities which increase their risk of acquiring infections. Infection control practices are geared towards reduction of occurrence and transmission of infectious diseases. OBJECTIVE: To evaluate knowledge and attitudes of infection prevention and control among Health Science students at University of Namibia. METHODS: To assess students' knowledge and attitudes regarding infection prevention and control and their sources of information, a self-administered questionnaire was used to look at standard precautions especially hands hygiene. RESULTS: One hundred sixty two students participated in this study of which 31 were medical, 17 were radiography and 114 were nursing students. Medical students had better overall scores (73%) compared to nursing students (66%) and radiology students (61%). There was no significant difference in scores between sexes or location of the high school being either in rural or urban setting. CONCLUSION: Serious efforts are needed to improve or review curriculum so that health sciences students' knowledge on infection prevention and control is imparted early before they are introduced to the wards.",,"['Ojulong, J', 'Mitonga, KH', 'Iipinge, SN']",,,,
,PMC,Differential expressed genes in ECV304 Endothelial-like Cells infected with Human Cytomegalovirus,http://dx.doi.org/10.4314/ahs.v13i4.2,PMC4056481,,,"BACKGROUND: Human cytomegalovirus (HCMV) is a virus which has the potential to alter cellular gene expression through multiple mechanisms. OBJECTIVE: With the application of DNA microarrays, we could monitor the effects of pathogens on host-cell gene expression programmes in great depth and on a broad scale. METHODS: Changes in mRNA expression levels of human endothelial-like ECV304 cells following infection with human cytomegalovirus AD169 strain was analyzed by a microarray system comprising 21073 60-mer oligonucleotide probes which represent 18716 human genes or transcripts. RESULTS: The results from cDNA microarray showed that there were 559 differential expressed genes consisted of 471 upregulated genes and 88 down-regulated genes. Real-time qPCR was performed to validate the expression of 6 selected genes (RPS24, MGC8721, SLC27A3, MST4, TRAF2 and LRRC28), and the results of which were consistent with those from the microarray. Among 237 biology processes, 39 biology processes were found to be related significantly to HCMV-infection. The signal transduction is the most significant biological process with the lowest p value (p=0.005) among all biological process which involved in response to HCMV infection. CONCLUSION: Several of these gene products might play key roles in virus-induced pathogenesis. These findings may help to elucidate the pathogenic mechanisms of HCMV caused diseases.",,"['Zhang, Yali', 'Ma, Wenli', 'Mo, Xiaoyang', 'Zhao, Haiquan', 'Zheng, Huanying', 'Ke, Changwen', 'Zheng, Wenling', 'Tu, Yanyang', 'Zhang, Yongsheng']",,,,
,PMC,Identification of novel drug scaffolds for inhibition of SARS-CoV 3-Chymotrypsin-like protease using virtual and high-throughput screenings,http://dx.doi.org/10.1016/j.bmc.2013.11.041,PMC3971864,,,"We have used a combination of virtual screening (VS) and high-throughput screening (HTS) techniques to identify novel, non-peptidic small molecule inhibitors against human SARS-CoV 3CLpro. A structure-based VS approach integrating docking and pharmacophore based methods was employed to computationally screen 621,000 compounds from the ZINC library. The screening protocol was validated using known 3CLpro inhibitors and was optimized for speed, improved selectivity, and for accommodating receptor flexibility. Subsequently, a fluorescence-based enzymatic HTS assay was developed and optimized to experimentally screen approximately 41,000 compounds from four structurally diverse libraries chosen mainly based on the VS results. False positives from initial HTS hits were eliminated by a secondary orthogonal binding analysis using surface plasmon resonance (SPR). The campaign identified a reversible small molecule inhibitor exhibiting mixed-type inhibition with a K(i) value of 11.1 μM. Together, these results validate our protocols as suitable approaches to screen virtual and chemical libraries, and the newly identified compound reported in our study represents a promising structural scaffold to pursue for further SARS-CoV 3CLpro inhibitor development.",,"['Lee, Hyun', 'Mittal, Anuradha', 'Patel, Kavankumar', 'Gatuz, Joseph L.', 'Truong, Lena', 'Torres, Jaime', 'Mulhearn, Debbie C.', 'Johnson, Michael E.']",,,,
,PMC,Public health management of mass gatherings: the Saudi Arabian experience with MERS-CoV,http://dx.doi.org/10.2471/BLT.13.132266,PMC3845273,,,,,"['Memish, Ziad A', 'Al-Rabeeah, Abdullah A']",,,,
,PMC,"Better Tests, Better Care: Improved Diagnostics for Infectious Diseases",http://dx.doi.org/10.1093/cid/cit578,PMC3820169,,,"In this IDSA policy paper, we review the current diagnostic landscape, including unmet needs and emerging technologies, and assess the challenges to the development and clinical integration of improved tests. To fulfill the promise of emerging diagnostics, IDSA presents recommendations that address a host of identified barriers. Achieving these goals will require the engagement and coordination of a number of stakeholders, including Congress, funding and regulatory bodies, public health agencies, the diagnostics industry, healthcare systems, professional societies, and individual clinicians.",,"['Caliendo, Angela M.', 'Gilbert, David N.', 'Ginocchio, Christine C.', 'Hanson, Kimberly E.', 'May, Larissa', 'Quinn, Thomas C.', 'Tenover, Fred C.', 'Alland, David', 'Blaschke, Anne J.', 'Bonomo, Robert A.', 'Carroll, Karen C.', 'Ferraro, Mary Jane', 'Hirschhorn, Lisa R.', 'Joseph, W. Patrick', 'Karchmer, Tobi', 'MacIntyre, Ann T.', 'Reller, L. Barth', 'Jackson, Audrey F.', None]",,,,
,PMC,The Microbiome and Its Impact on Disease in the Preterm Patient,http://dx.doi.org/10.1007/s40124-013-0031-7,PMC4240619,,,"Emerging technologies derived largely from the Human Genome Project are being applied to evaluating the intestinal microbiota in preterm infants. The microbial ecology of the developing intestine is highly related to health and disease and new discoveries are emerging that will help us understand disorders in the development of the intestinal microbial ecosystem and how to eventually manipulate them to prevent diseases such as necrotizing enterocolitis and late onset sepsis. Here, a brief overview of the developing microbiome as it pertains to several aspects of health and disease in the preterm infant is presented.",,"Neu, Josef",,,,
,PMC,Future Treatment Strategies for Novel Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.4155/fmc.13.183,PMC4085789,,,,,"['Adedeji, Adeyemi O.', 'Sarafianos, Stefan G.']",,,,
,PMC,Detection of Canine Pneumovirus in Dogs with Canine Infectious Respiratory Disease,http://dx.doi.org/10.1128/JCM.02312-13,PMC3838075,,,"Canine pneumovirus (CnPnV) was recently identified during a retrospective survey of kenneled dogs in the United States. In this study, archived samples from pet and kenneled dogs in the United Kingdom were screened for CnPnV to explore the relationship between exposure to CnPnV and the development of canine infectious respiratory disease (CIRD). Within the pet dog population, CnPnV-seropositive dogs were detected throughout the United Kingdom and Republic of Ireland, with an overall estimated seroprevalence of 50% (n = 314/625 dogs). In the kennel population, there was a significant increase in seroprevalence, from 26% (n = 56/215 dogs) on the day of entry to 93.5% (n = 201/215 dogs) after 21 days (P <0001). Dogs that were seronegative on entry but seroconverted while in the kennel were 4 times more likely to develop severe respiratory disease than those that did not seroconvert (P < 0.001), and dogs with preexisting antibodies to CnPnV on the day of entry were significantly less likely to develop respiratory disease than immunologically naive dogs (P < 0.001). CnPnV was detected in the tracheal tissues of 29/205 kenneled dogs. Detection was most frequent in dogs with mild to moderate respiratory signs and histopathological changes and in dogs housed for 8 to 14 days, which coincided with a significant increase in the risk of developing respiratory disease compared to the risk of those housed 1 to 7 days (P < 0.001). These findings demonstrate that CnPnV is present in the United Kingdom dog population; there is a strong association between exposure to CnPnV and CIRD in the kennel studied and a potential benefit in vaccinating against CnPnV as part of a wider disease prevention strategy.",,"['Mitchell, Judy A.', 'Cardwell, Jacqueline M.', 'Renshaw, Randall W.', 'Dubovi, Edward J.', 'Brownlie, Joe']",,,,
,PMC,Evaluation and Implementation of FilmArray Version 1.7 for Improved Detection of Adenovirus Respiratory Tract Infection,http://dx.doi.org/10.1128/JCM.02546-13,PMC3838020,,,"The BioFire FilmArray respiratory panel is a multiplex PCR technology capable of detecting a number of bacteria and viruses that cause respiratory tract infection. The assay is technically simple to perform and provides rapid results, making it an appealing option for physicians and laboratorians. The initial product released by BioFire (version 1.6) was reported to have poor sensitivity for adenovirus detection and was therefore of concern when testing immunocompromised patients. This study evaluates the redesigned FilmArray assay (version 1.7) for detection of adenovirus. In this evaluation, we performed both retrospective and prospective verification studies, as well as a detailed serotype analysis. We found that version 1.7 demonstrated improved adenovirus sensitivity. In retrospective studies, sensitivity improved from 66.6% to 90.5%, and in prospective studies, it improved from 42.7% to 83.3%. In addition, when 39 clinically relevant serotypes were tested, 8 were not detected by version 1.6 and only 1 was not detected by version 1.7. The limit of detection remained the same when tested against serotype 4 but improved by 2 log units for serotype 7. Lastly, turnaround time analyses showed that the FilmArray assay was completed 3 h and 9 min after collection, which was more than a 37-h improvement over the previous multiplex PCR assay performed in our laboratory.",,"['Doern, Christopher D.', 'Lacey, Damon', 'Huang, Rong', 'Haag, Crissie']",,,,
,PMC,"Kolente virus, a rhabdovirus species isolated from ticks and bats in the Republic of Guinea",http://dx.doi.org/10.1099/vir.0.055939-0,PMC3836499,,,"Kolente virus (KOLEV) is a rhabdovirus originally isolated from ticks and a bat in Guinea, West Africa, in 1985. Although tests at the time of isolation suggested that KOLEV is a novel rhabdovirus, it has remained largely uncharacterized. We assembled the complete genome sequence of the prototype strain DakAr K7292, which was found to encode the five canonical rhabdovirus structural proteins (N, P, M, G and L) with alternative ORFs (>180 nt) in the P and L genes. Serologically, KOLEV exhibited a weak antigenic relationship with Barur and Fukuoka viruses in the Kern Canyon group. Phylogenetic analysis revealed that KOLEV represents a distinct and divergent lineage that shows no clear relationship to any rhabdovirus except Oita virus, although with limited phylogenetic resolution. In summary, KOLEV represents a novel species in the family Rhabdoviridae.",,"['Ghedin, Elodie', 'Rogers, Matthew B.', 'Widen, Steven G.', 'Guzman, Hilda', 'Travassos da Rosa, Amelia P. A.', 'Wood, Thomas G.', 'Fitch, Adam', 'Popov, Vsevolod', 'Holmes, Edward C.', 'Walker, Peter J.', 'Vasilakis, Nikos', 'Tesh, Robert B.']",,,,
,PMC,Emerging Roles for Immunomodulatory Functions of Free ISG15,http://dx.doi.org/10.1089/jir.2013.0064,PMC3868375,,,"Type I interferons (IFNs) exert their effects through the induction of hundreds of IFN-stimulated genes (ISGs), many of which function by inhibiting viral replication and modulating immune responses. ISG15, a di-ubiquitin-like protein, is one of the most abundantly induced ISGs and is critical for control of certain viral and bacterial infections. Like ubiquitin, ISG15 is covalently conjugated to target proteins. In addition, free unconjugated ISG15 is present both intra- and extracellularly. Although much remains to be learned about conjugated ISG15, even less is known about the 2 free forms of ISG15. This article focuses on the role that ISG15 plays during the host response to pathogen challenge, in particular on the recent observations describing the immunomodulatory properties of free ISG15 and its potential implication in disease pathogenesis.",,"['Campbell, Jessica A.', 'Lenschow, Deborah J.']",,,,
,PMC,Critical care medicine 2013: a review and prospect,http://dx.doi.org/10.3978/j.issn.2072-1439.2013.12.51,PMC3886708,,,,,"Huang, Wei",,,,
,PMC,Highly Divergent Strains of Porcine Reproductive and Respiratory Syndrome Virus Incorporate Multiple Isoforms of Nonstructural Protein 2 into Virions,http://dx.doi.org/10.1128/JVI.02435-13,PMC3838290,,,"Viral structural proteins form the critical intermediary between viral infection cycles within and between hosts, function to initiate entry, participate in immediate early viral replication steps, and are major targets for the host adaptive immune response. We report the identification of nonstructural protein 2 (nsp2) as a novel structural component of the porcine reproductive and respiratory syndrome virus (PRRSV) particle. A set of custom α-nsp2 antibodies targeting conserved epitopes within four distinct regions of nsp2 (the PLP2 protease domain [OTU], the hypervariable domain [HV], the putative transmembrane domain [TM], and the C-terminal region [C]) were obtained commercially and validated in PRRSV-infected cells. Highly purified cell-free virions of several PRRSV strains were isolated through multiple rounds of differential density gradient centrifugation and analyzed by immunoelectron microscopy (IEM) and Western blot assays using the α-nsp2 antibodies. Purified viral preparations were found to contain pleomorphic, predominantly spherical virions of uniform size (57.9 nm ± 8.1 nm diameter; n = 50), consistent with the expected size of PRRSV particles. Analysis by IEM indicated the presence of nsp2 associated with the viral particle of diverse strains of PRRSV. Western blot analysis confirmed the presence of nsp2 in purified viral samples and revealed that multiple nsp2 isoforms were associated with the virion. Finally, a recombinant PRRSV genome containing a myc-tagged nsp2 was used to generate purified virus, and these particles were also shown to harbor myc-tagged nsp2 isoforms. Together, these data identify nsp2 as a virion-associated structural PRRSV protein and reveal that nsp2 exists in or on viral particles as multiple isoforms.",,"['Kappes, Matthew A.', 'Miller, Cathy L.', 'Faaberg, Kay S.']",,,,
,PMC,Suppression of PACT-Induced Type I Interferon Production by Herpes Simplex Virus 1 Us11 Protein,http://dx.doi.org/10.1128/JVI.02564-13,PMC3838286,,,"Herpes simplex virus 1 (HSV-1) Us11 protein is a double-stranded RNA-binding protein that suppresses type I interferon production through the inhibition of the cytoplasmic RNA sensor RIG-I. Whether additional cellular mediators are involved in this suppression remains to be determined. In this study, we report on the requirement of cellular double-stranded RNA-binding protein PACT for Us11-mediated perturbation of type I interferon production. Us11 associates with PACT tightly to prevent it from binding with and activating RIG-I. The Us11-deficient HSV-1 was indistinguishable from the Us11-proficient virus in the suppression of interferon production when PACT was compromised. More importantly, HSV-1-induced activation of interferon production was abrogated in PACT knockout murine embryonic fibroblasts. Our findings suggest a new mechanism for viral evasion of innate immunity through which a viral double-stranded RNA-binding protein interacts with PACT to circumvent type I interferon production. This mechanism might also be used by other PACT-binding viral interferon-antagonizing proteins such as Ebola virus VP35 and influenza A virus NS1.",,"['Kew, Chun', 'Lui, Pak-Yin', 'Chan, Chi-Ping', 'Liu, Xiang', 'Au, Shannon Wing Ngor', 'Mohr, Ian', 'Jin, Dong-Yan', 'Kok, Kin-Hang']",,,,
,PMC,Merkel Cell Polyomavirus Small T Antigen Targets the NEMO Adaptor Protein To Disrupt Inflammatory Signaling,http://dx.doi.org/10.1128/JVI.02159-13,PMC3838273,,,"Merkel cell carcinoma (MCC) is a highly aggressive nonmelanoma skin cancer arising from epidermal mechanoreceptor Merkel cells. In 2008, a novel human polyomavirus, Merkel cell polyomavirus (MCPyV), was identified and is strongly implicated in MCC pathogenesis. Currently, little is known regarding the virus-host cell interactions which support virus replication and virus-induced mechanisms in cellular transformation and metastasis. Here we identify a new function of MCPyV small T antigen (ST) as an inhibitor of NF-κB-mediated transcription. This effect is due to an interaction between MCPyV ST and the NF-κB essential modulator (NEMO) adaptor protein. MCPyV ST expression inhibits IκB kinase α (IKKα)/IKKβ-mediated IκB phosphorylation, which limits translocation of the NF-κB heterodimer to the nucleus. Regulation of this process involves a previously undescribed interaction between MCPyV ST and the cellular phosphatase subunits, protein phosphatase 4C (PP4C) and/or protein phosphatase 2A (PP2A) Aβ, but not PP2A Aα. Together, these results highlight a novel function of MCPyV ST to subvert the innate immune response, allowing establishment of early or persistent infection within the host cell.",,"['Griffiths, David A.', 'Abdul-Sada, Hussein', 'Knight, Laura M.', 'Jackson, Brian R.', 'Richards, Kathryn', 'Prescott, Emma L.', 'Peach, A. Howard S.', 'Blair, G. Eric', 'Macdonald, Andrew', 'Whitehouse, Adrian']",,,,
,PMC,Inhibition of Middle East Respiratory Syndrome Coronavirus Infection by Anti-CD26 Monoclonal Antibody,http://dx.doi.org/10.1128/JVI.02448-13,PMC3838260,,,"We identified the domains of CD26 involved in the binding of Middle East respiratory syndrome coronavirus (MERS-CoV) using distinct clones of anti-CD26 monoclonal antibodies (MAbs). One clone, named 2F9, almost completely inhibited viral entry. The humanized anti-CD26 MAb YS110 also significantly inhibited infection. These findings indicate that both 2F9 and YS110 are potential therapeutic agents for MERS-CoV infection. YS110, in particular, is a good candidate for immediate testing as a therapeutic modality for MERS.",,"['Ohnuma, Kei', 'Haagmans, Bart L.', 'Hatano, Ryo', 'Raj, V. Stalin', 'Mou, Huihui', 'Iwata, Satoshi', 'Dang, Nam H.', 'Bosch, Berend Jan', 'Morimoto, Chikao']",,,,
,PMC,Structure of the Fusion Core and Inhibition of Fusion by a Heptad Repeat Peptide Derived from the S Protein of Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.02433-13,PMC3838252,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) recently emerged as a severe worldwide public health concern. The virus is highly pathogenic, manifesting in infected patients with an approximately 50% fatality rate. It is known that the surface spike (S) proteins of coronaviruses mediate receptor recognition and membrane fusion, thereby playing an indispensable role in initiating infection. In this process, heptad repeats 1 and 2 (HR1 and HR2) of the S protein assemble into a complex called the fusion core, which represents a key membrane fusion architecture. To date, however, the MERS-CoV fusion core remains uncharacterized. In this study, we performed a series of biochemical and biophysical analyses characterizing the HR1/HR2 complexes of this novel virus. The HR sequences were variably truncated and then connected with a flexible amino acid linker. In each case, the recombinant protein automatically assembled into a trimer in solution, displaying a typical α-helical structure. One of these trimers was successfully crystallized, and its structure was solved at a resolution of 1.9 Å. A canonical 6-helix bundle, like those reported for other coronaviruses, was revealed, with three HR1 helices forming the central coiled-coil core and three HR2 chains surrounding the core in the HR1 side grooves. This demonstrates that MERS-CoV utilizes a mechanism similar to those of other class I enveloped viruses for membrane fusion. With this notion, we further identified an HR2-based peptide that could potently inhibit MERS-CoV fusion and entry by using a pseudotyped-virus system. These results lay the groundwork for future inhibitory peptidic drug design.",,"['Gao, Jing', 'Lu, Guangwen', 'Qi, Jianxun', 'Li, Yan', 'Wu, Ying', 'Deng, Yao', 'Geng, Heyuan', 'Li, Hongbin', 'Wang, Qihui', 'Xiao, Haixia', 'Tan, Wenjie', 'Yan, Jinghua', 'Gao, George F.']",,,,
,PMC,"Surface Glycoproteins of an African Henipavirus Induce Syncytium Formation in a Cell Line Derived from an African Fruit Bat, Hypsignathus monstrosus",http://dx.doi.org/10.1128/JVI.02458-13,PMC3838219,,,"Serological screening and detection of genomic RNA indicates that members of the genus Henipavirus are present not only in Southeast Asia but also in African fruit bats. We demonstrate that the surface glycoproteins F and G of an African henipavirus (M74) induce syncytium formation in a kidney cell line derived from an African fruit bat, Hypsignathus monstrosus. Despite a less broad cell tropism, the M74 glycoproteins show functional similarities to glycoproteins of Nipah virus.",,"['Krüger, Nadine', 'Hoffmann, Markus', 'Weis, Michael', 'Drexler, Jan Felix', 'Müller, Marcel Alexander', 'Winter, Christine', 'Corman, Victor Max', 'Gützkow, Tim', 'Drosten, Christian', 'Maisner, Andrea', 'Herrler, Georg']",,,,
,PMC,White Spot Syndrome Virus IE1 and WSV056 Modulate the G(1)/S Transition by Binding to the Host Retinoblastoma Protein,http://dx.doi.org/10.1128/JVI.01551-13,PMC3838160,,,"DNA viruses often target cellular proteins to modulate host cell cycles and facilitate viral genome replication. However, whether proliferation of white spot syndrome virus (WSSV) requires regulation of the host cell cycle remains unclear. In the present study, we show that two WSSV paralogs, IE1 and WSV056, can interact with Litopenaeus vannamei retinoblastoma (Rb)-like protein (lv-RBL) through the conserved LxCxE motif. Further investigation revealed that IE1 and WSV056 could also bind to Drosophila retinoblastoma family protein 1 (RBF1) in a manner similar to how they bind to lv-RBL. Using the Drosophila RBF-E2F pathway as a model system, we demonstrated that both IE1 and WSV056 could sequester RBF1 from Drosophila E2F transcription factor 1 (E2F1) and subsequently activate E2F1 to stimulate the G(1)/S transition. Our findings provide the first evidence that WSSV may regulate cell cycle progression by targeting the Rb-E2F pathway.",,"['Ran, Xiaozhuo', 'Bian, Xiaofang', 'Ji, Yongchang', 'Yan, Xiumin', 'Yang, Feng', 'Li, Fang']",,,,
,PMC,Nonstructural Protein σ1s Mediates Reovirus-Induced Cell Cycle Arrest and Apoptosis,http://dx.doi.org/10.1128/JVI.02080-13,PMC3838159,,,"Reovirus nonstructural protein σ1s is implicated in cell cycle arrest at the G(2)/M boundary and induction of apoptosis. However, the contribution of σ1s to these effects in an otherwise isogenic viral background has not been defined. To evaluate the role of σ1s in cell cycle arrest and apoptosis, we used reverse genetics to generate a σ1s-null reovirus. Following infection with wild-type virus, we observed an increase in the percentage of cells in G(2)/M, whereas the proportion of cells in G(2)/M following infection with the σ1s-null mutant was unaffected. Similarly, we found that the wild-type virus induced substantially greater levels of apoptosis than the σ1s-null mutant. These data indicate that σ1s is required for both reovirus-induced cell cycle arrest and apoptosis. To define sequences in σ1s that mediate these effects, we engineered viruses encoding C-terminal σ1s truncations by introducing stop codons in the σ1s open reading frame. We also generated viruses in which charged residues near the σ1s amino terminus were replaced individually or as a cluster with nonpolar residues. Analysis of these mutants revealed that amino acids 1 to 59 and the amino-terminal basic cluster are required for induction of both cell cycle arrest and apoptosis. Remarkably, viruses that fail to induce cell cycle arrest and apoptosis also are attenuated in vivo. Thus, identical sequences in σ1s are required for reovirus-induced cell cycle arrest, apoptosis, and pathogenesis. Collectively, these findings provide evidence that the σ1s-mediated properties are genetically linked and suggest that these effects are mechanistically related.",,"['Boehme, Karl W.', 'Hammer, Katharina', 'Tollefson, William C.', 'Konopka-Anstadt, Jennifer L.', 'Kobayashi, Takeshi', 'Dermody, Terence S.']",,,,
,PMC,Herpes Simplex Virus 1 Serine/Threonine Kinase US3 Hyperphosphorylates IRF3 and Inhibits Beta Interferon Production,http://dx.doi.org/10.1128/JVI.02355-13,PMC3838156,,,"Viral infection initiates a series of signaling cascades that lead to the transcription of interferons (IFNs), finally inducing interferon-stimulated genes (ISGs) to eliminate viruses. Viruses have evolved a variety of strategies to modulate host IFN-mediated immune responses. Herpes simplex virus 1 (HSV-1) US3, a Ser/Thr kinase conserved in alphaherpesviruses, was previously reported to counteract host innate immunity; however, the molecular mechanism is elusive. In this study, we report that US3 blocks IFN-β production by hyperphosphorylating IFN regulatory factor 3 (IRF3). Ectopic expression of US3 protein significantly inhibited Sendai virus (SeV)-mediated activation of IFN-β and IFN-stimulated response element (ISRE) promoters and the transcription of IFN-β, ISG54, and ISG56. US3 was also shown to block SeV-induced dimerization and nuclear translocation of IRF3. The kinase activity was indispensable for its inhibitory function, as kinase-dead (KD) US3 mutants K220M and D305A could not inhibit IFN-β production. Furthermore, US3 interacted with and hyperphosphorylated IRF3 at Ser175 to prevent IRF3 activation. Finally, the US3 KD mutant viruses were constructed and denoted K220M or D305A HSV-1, respectively. Cells and mice infected with both mutant viruses produced remarkably larger amounts of IFN-β than those infected with wild-type HSV-1. For the first time, these findings provide convincing evidence that US3 hyperphosphorylates IRF3, blocks the production of IFN-β, and subverts host innate immunity.",,"['Wang, Shuai', 'Wang, Kezhen', 'Lin, Rongtuan', 'Zheng, Chunfu']",,,,
,PMC,Middle East Respiratory Syndrome Coronavirus Infection Mediated by the Transmembrane Serine Protease TMPRSS2,http://dx.doi.org/10.1128/JVI.01890-13,PMC3838146,,,"The Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes host proteases for virus entry into lung cells. In the current study, Vero cells constitutively expressing type II transmembrane serine protease (Vero-TMPRSS2 cells) showed larger syncytia at 18 h after infection with MERS-CoV than after infection with other coronaviruses. Furthermore, the susceptibility of Vero-TMPRSS2 cells to MERS-CoV was 100-fold higher than that of non-TMPRSS2-expressing parental Vero cells. The serine protease inhibitor camostat, which inhibits TMPRSS2 activity, completely blocked syncytium formation but only partially blocked virus entry into Vero-TMPRSS2 cells. Importantly, the coronavirus is thought to enter cells via two distinct pathways, one mediated by TMPRSS2 at the cell surface and the other mediated by cathepsin L in the endosome. Simultaneous treatment with inhibitors of cathepsin L and TMPRSS2 completely blocked virus entry into Vero-TMPRSS2 cells, indicating that MERS-CoV employs both the cell surface and the endosomal pathway to infect Vero-TMPRSS2 cells. In contrast, a single camostat treatment suppressed MERS-CoV entry into human bronchial submucosal gland-derived Calu-3 cells by 10-fold and virus growth by 270-fold, although treatment with both camostat and (23,25)-trans-epoxysuccinyl-l-leucylamindo-3-methylbutane ethyl ester, a cathepsin inhibitor, or treatment with leupeptin, an inhibitor of cysteine, serine, and threonine peptidases, was no more efficacious than treatment with camostat alone. Further, these inhibitors were not efficacious against MERS-CoV infection of MRC-5 and WI-38 cells, which were derived from lung, but these characters differed from those of mature pneumocytes. These results suggest that a single treatment with camostat is sufficient to block MERS-CoV entry into a well-differentiated lung-derived cell line.",,"['Shirato, Kazuya', 'Kawase, Miyuki', 'Matsuyama, Shutoku']",,,,
,PMC,Chimeric Exchange of Coronavirus nsp5 Proteases (3CLpro) Identifies Common and Divergent Regulatory Determinants of Protease Activity,http://dx.doi.org/10.1128/JVI.02050-13,PMC3838113,,,"Human coronaviruses (CoVs) such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) cause epidemics of severe human respiratory disease. A conserved step of CoV replication is the translation and processing of replicase polyproteins containing 16 nonstructural protein domains (nsp's 1 to 16). The CoV nsp5 protease (3CLpro; Mpro) processes nsp's at 11 cleavage sites and is essential for virus replication. CoV nsp5 has a conserved 3-domain structure and catalytic residues. However, the intra- and intermolecular determinants of nsp5 activity and their conservation across divergent CoVs are unknown, in part due to challenges in cultivating many human and zoonotic CoVs. To test for conservation of nsp5 structure-function determinants, we engineered chimeric betacoronavirus murine hepatitis virus (MHV) genomes encoding nsp5 proteases of human and bat alphacoronaviruses and betacoronaviruses. Exchange of nsp5 proteases from HCoV-HKU1 and HCoV-OC43, which share the same genogroup, genogroup 2a, with MHV, allowed for immediate viral recovery with efficient replication albeit with impaired fitness in direct competition with wild-type MHV. Introduction of MHV nsp5 temperature-sensitive mutations into chimeric HKU1 and OC43 nsp5 proteases resulted in clear differences in viability and temperature-sensitive phenotypes compared with MHV nsp5. These data indicate tight genetic linkage and coevolution between nsp5 protease and the genomic background and identify differences in intramolecular networks regulating nsp5 function. Our results also provide evidence that chimeric viruses within coronavirus genogroups can be used to test nsp5 determinants of function and inhibition in common isogenic backgrounds and cell types.",,"['Stobart, Christopher C.', 'Sexton, Nicole R.', 'Munjal, Havisha', 'Lu, Xiaotao', 'Molland, Katrina L.', 'Tomar, Sakshi', 'Mesecar, Andrew D.', 'Denison, Mark R.']",,,,
,PMC,A Polyclonal Antibody Against Recombinant Bovine Haptoglobin Expressed in Escherichia coli,http://dx.doi.org/10.1089/mab.2013.0061,PMC3869540,,,"The nucleotide sequence of the predicted immunodominant region of bovine haptoglobin (pirBoHp), without the signal peptide sequence, was synthesized based on the codon usage bias of Escherichia coli. The synthesized pirBoHp gene was cloned into the prokaryotic expression vector pET-32a (+), which contains a His-tag. The recombinant pirBoHp protein was successfully expressed in E. coli BL21 (DE3) cells. Western blot analysis showed that the purified recombinant pirBoHp protein could be recognized by an anti-His-tag monoclonal antibody. Further investigations indicated that a polyclonal antibody against the recombinant pirBoHp protein could recognize the α and β chains of native bovine haptoglobin in a pooled plasma sample from dairy cattle suffering from foot rot.",,"['Guo, Donghua', 'Zhang, Hong', 'Li, Chunqiu', 'Sun, Dongbo']",,,,
,PMC,"Novel Inflammatory Markers, Clinical Risk Factors, and Virus Type Associated with Severe Respiratory Syncytial Virus Infection",http://dx.doi.org/10.1097/INF.0b013e3182a14407,PMC3883981,,,"BACKGROUND: Virus-induced inflammation contributes to respiratory syncytial virus (RSV) pathogenesis. We sought to determine the specific mediators that are associated with more severe illness in young children. METHODS: Children ≤ 5 yrs of age seen in our emergency department for respiratory symptoms from September 1998 to May 2008 were eligible for enrollment. Nasopharyngeal (NP) wash samples were collected from all eligible patients, and clinical data were recorded. Individuals were included in this study if NP wash samples were positive for RSV only. Patients enrolled in the study were stratified by disease severity, defined as mild (not hospitalized), moderate (hospitalized), or severe (requiring ICU stay). Concentrations of individual inflammatory biomarkers in NP wash fluids were determined using the Luminex human 30-plex assay. RESULTS: 851 patients met study criteria; 268 (31.5%) with mild, 503 (59.1%) with moderate, and 80 (9.4%) with severe illness. As expected, illness severity was directly associated with young age, prematurity, heart or lung disease, infection with RSV group A, and elevated concentrations of interleukin (IL)-2R, IL-6, CXCL8, tumor necrosis factor (TNF)-α, interferon (IFN)-α, CCL3, CCL4, and CCL2. In addition, we report several novel and mechanistically important inflammatory biomarkers of severe RSV disease, including IL-1β, IL1-RA, IL-7, epidermal growth factor (EGF), and hepatocyte growth factor (HGF). CONCLUSIONS: In a large, longitudinal study (10 years, 851 enrolled patients) limited to RSV infection only, in which well-known risk factors are confirmed, we identified five novel biomarkers specifically of severe disease. These markers may ultimately serve to elucidate disease mechanisms.",,"['Tabarani, Christy M.', 'Bonville, Cynthia A.', 'Suryadevara, Manika', 'Branigan, Patrick', 'Wang, Dongliang', 'Huang, Danning', 'Rosenberg, Helene F.', 'Domachowske, Joseph B.']",,,,
,PMC,Extracts of medicinal herb Sanguisorba officinalis inhibit the entry of human immunodeficiency virus type one,http://dx.doi.org/10.1016/j.jfda.2013.09.034,PMC4151571,,,"Highly active antiretroviral therapy (HAART) has been successful in reducing HIV-1-associated morbidity and mortality since its introduction in 1996. It, however, fails to eradicate HIV-1 infection thoroughly. The high cost of life-long HAART and the emergence of drug resistance among HIV-1-infected individuals have brought renewed pressure for the discovery of novel antivirals and alternative medicines. Traditional Chinese medicine (TCM) is one of the mainstreams of complementary and alternative medicine, and serves as rich resources for new drug development. Despite almost 100 plant-derived compounds are in clinical trials, few target HIV-1 infection. In this study, we discovered that extract of Sanguisorba officinalis (SOE) has anti-HIV-1 activities. Using a cell-based assay and single-cycle luciferase reporter viruses pseudotyped with envelopes from HIV-1 or control viruses, we found that SOE exhibited significant inhibitory ability against both CCR5 and CXCR4 tropic HIV-1 (ADA and HXB2) with respective IC(50) values of 1.91±0.16 μg/ml and 3.70±0.53 μg/ml. Interestingly, SOE also inhibited SIV infection but failed to block vesicular stomatitis virus (VSV), SARS-CoV and influeunza H5N1 pseudoviruses. Furthermore, we showed that SOE had no effects on post-entry events of HIV-1 replication. It blocked entry by acting on viral envelope directly because SOE pre-treatment with the virus but not with cell lines expressing viral receptors showed the maximal inhibitory activity. In addition, SOE was able to inhibit reverse-transcription-inhibitor-resistant viruses (K103N, Y188L, and K103N/Y188L/G190A) and a protease-inhibitor-resistant strain (PI-2840). Our findings demonstrated SOE as a novel and specific entry inhibitor, which shed lights on the discovery of anti-HIV-1 drugs from traditional herbal medicines.",,"['Liang, Jianguo', 'Chen, Jianping', 'Tan, Zhiwu', 'Peng, Jie', 'Zheng, Xiao', 'Nishiura, Kenji', 'Ng, Jenny', 'Wang, Zhiyu', 'Wang, Dongmei', 'Chen, Zhiwei', 'Liu, Li']",,,,
,PMC,The Human IgE Repertoire,http://dx.doi.org/10.1159/000355947,PMC4497803,,,"IgE is a key mediator in allergic diseases. However, in strong contrast to other antibody isotypes, many details of the composition of the human IgE repertoire are poorly defined. The low levels of human IgE in the circulation and the rarity of IgE-producing B cells are important reasons for this lack of knowledge. In this review, we summarize the current knowledge on these repertoires both in terms of their complexity and activity, i.e. knowledge which despite the difficulties encountered when studying the molecular details of human IgE has been acquired in recent years. We also take a look at likely future developments, for instance through improvements in sequencing technology and methodology that allow the isolation of additional allergen-specific human antibodies mimicking IgE, as this certainly will support our understanding of human IgE in the context of human disease in the years to come.",,"['Gadermaier, Elisabeth', 'Levin, Mattias', 'Flicker, Sabine', 'Ohlin, Mats']",,,,
,PMC,CD8(+) T cell independent tumor regression induced by Fc-OX40L and therapeutic vaccination in a mouse model of glioma,http://dx.doi.org/10.4049/jimmunol.1301633,PMC4068509,,,"Despite the growing number of pre-clinical and clinical trials focused on immunotherapy for the treatment of malignant gliomas, the prognosis for this disease remains grim. Although some promising advances have been made, the immune response stimulated as a result of immunotherapeutic protocols has been inefficient at complete tumor elimination, primarily due to our lack of understanding of the necessary effector functions of the immune system. We previously demonstrated that a tumor lysate vaccine/Fc-OX40L therapy is capable of inducing enhanced survival and tumor elimination in the GL261 mouse glioma model. The following experiments were performed to determine the mechanism(s) of action of this therapy that elicits a potent anti-tumor immune response. The evidence subsequently outlined indicates a CD8(+) T cell independent and CD4(+) T cell, NK cell, and B cell dependent means of prolonged survival. CD8(+) T cell independent tumor clearance is surprising considering the current focus of many cancer immunotherapy protocols. These results provide evidence for CD8(+) T cell independent means of anti-tumor response and should lead to additional examination of the potential manipulation of this mechanism for future treatment strategies.",,"['Murphy, Katherine A.', 'Erickson, Jami R.', 'Johnson, Charles S.', 'Seiler, Charles E.', 'Bedi, Jessica', 'Hu, Peisheng', 'Pluhar, G. Elizabeth', 'Epstein, Alan L.', 'Ohlfest, John R.']",,,,
,PMC,Regulatory T cells as adjuvant target for enhancing the viral disease vaccine efficacy,http://dx.doi.org/10.1007/s13337-013-0187-3,PMC3889236,,,"CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) are critical for immune homeostasis and tolerance. However, because of their capacity to suppress antigen presenting cells (APC), T and B cells, Tregs could also inhibit protective immune responses to viruses and vaccines. Several viruses have been shown to exploit Tregs to evade immune response. By modulating APC and in particular by weakening the functions of dendritic cells such as their ability to secrete polarizing cytokines and expression of co-stimulatory molecules, viruses could support differentiation and expansion of Tregs. Of note, as a proof of concept, depletion of Tregs significantly enhanced the protective immune response to viruses and vaccines suggesting that Tregs are viable targets to enhance immunogenicity of vaccines. As Treg depletion or inhibition of their functions could lead to deleterious autoimmune and inflammatory disorders, any Treg-based approach for vaccination should not aim at depletion of Tregs and inhibition of their functions should be transient. Recent studies have targeted the interaction between CCR4 expressed on Tregs and its ligands CCL22 and CCL17 to inhibit transiently the recruitment of Tregs at the site of immunization. Importantly, use of CCR4 antagonists as ‘molecular adjuvants’ in vivo in experimental models, amplified cellular and humoral immune responses when injected in combination with various vaccine antigens. The significant adjuvant activity observed in diverse models without noticeable side effects provided strong evidence that CCR4 is a sustainable target for rational adjuvant design.",,"Bayry, Jagadeesh",,,,
,PMC,"A chemical free, nanotechnology-based method for airborne bacterial inactivation using engineered water nanostructures",http://dx.doi.org/10.1039/C3EN00007A,PMC4500755,,,"Airborne pathogens are associated with the spread of infectious diseases and increased morbidity and mortality. Herein we present an emerging chemical free, nanotechnology-based method for airborne pathogen inactivation. This technique is based on transforming atmospheric water vapor into Engineered Water Nano-Structures (EWNS) via electrospray. The generated EWNS possess a unique set of physical, chemical, morphological and biological properties. Their average size is 25 nm and they contain reactive oxygen species (ROS) such as hydroxyl and superoxide radicals. In addition, EWNS are highly electrically charged (10 electrons per particle on average). A link between their electric charge and the reduction of their evaporation rate was illustrated resulting in an extended lifetime (over an hour) at room conditions. Furthermore, it was clearly demonstrated that the EWNS have the ability to interact with and inactivate airborne bacteria. Finally, inhaled EWNS were found to have minimal toxicological effects, as illustrated in an acute in-vivo inhalation study using a mouse model. In conclusion, this novel, chemical free, nanotechnology-based method has the potential to be used in the battle against airborne infectious diseases.",,"['Pyrgiotakis, Georgios', 'McDevitt, James', 'Bordini, Andre', 'Diaz, Edgar', 'Molina, Ramon', 'Watson, Christa', 'Deloid, Glen', 'Lenard, Steve', 'Fix, Natalie', 'Mizuyama, Yosuke', 'Yamauchi, Toshiyuki', 'Brain, Joseph', 'Demokritou, Philip']",,,,
,PMC,Airborne exposure patterns from a passenger source in aircraft cabins,http://dx.doi.org/10.1080/10789669.2013.838990,PMC4626449,,,"Airflow is a critical factor that influences air quality, airborne contaminant distribution, and disease transmission in commercial airliner cabins. The general aircraft-cabin air-contaminant transport effect model seeks to build exposure-spatial relationships between contaminant sources and receptors, quantify the uncertainty, and provide a platform for incorporation of data from a variety of studies. Knowledge of infection risk to flight crews and passengers is needed to form a coherent response to an unfolding epidemic, and infection risk may have an airborne pathogen exposure component. The general aircraf-tcabin air-contaminant transport effect model was applied to datasets from the University of Illinois and Kansas State University and also to case study information from a flight with probable severe acute respiratory syndrome transmission. Data were fit to regression curves, where the dependent variable was contaminant concentration (normalized for source strength and ventilation rate), and the independent variable was distance between source and measurement locations. The data-driven model showed exposure to viable small droplets and post-evaporation nuclei at a source distance of several rows in a mock-up of a twin-aisle airliner with seven seats per row. Similar behavior was observed in tracer gas, particle experiments, and flight infection data for severe acute respiratory syndrome. The study supports the airborne pathway as part of the matrix of possible disease transmission modes in aircraft cabins.",,"['Bennett, James S.', 'Jones, Byron W.', 'Hosni, Mohammad H.', 'Zhang, Yuanhui', 'Topmiller, Jennifer L.', 'Dietrich, Watts L.']",,,,
,PMC,Role of Pathogens in Multiple Sclerosis,http://dx.doi.org/10.3109/08830185.2013.823422,PMC4369909,,,"Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease of the central nervous system (CNS). Although the etiology of MS is unknown, genetic and environmental factors play a role. Infectious pathogens are the likely environmental factors involved in the development of MS. Pathogens associated with the development or exacerbation of MS include bacteria, such as Mycoplasma pneumoniae and Chlamydia pneumoniae, the Staphylococcus aureus-produced enterotoxins that function as superantigens, viruses of the herpes virus (Epstein-Barr virus and human herpesvirus 6) and human endogenous retrovirus (HERV) families and the protozoa Acanthamoeba castellanii. Evidence, from studies with humans and animal models, supporting the association of these various pathogens with the development and/or exacerbation of MS will be discussed along with the potential mechanisms including molecular mimicry, epitope spreading and bystander activation. In contrast, infection with certain parasites such as helminthes (Schistosoma mansoni, Fasciola hepatica, Hymenolepis nana, Trichuris trichiura, Ascaris lumbricoides, Strongyloides stercolaris, Enterobius vermicularis) appears to protect against the development or exacerbation of MS. Evidence supporting the ability of parasitic infections to protect against disease will be discussed along with a brief summary of a recent Phase I clinical trial testing the ability of Trichuris suis ova treatment to improve the clinical course of MS. A complex interaction between the CNS (including the blood-brain barrier), multiple infections with various infectious agents (occurring in the periphery or within the CNS), and the immune response to those various infections may have to be deciphered before the etiology of MS can be fully understood.",,"['Libbey, Jane E.', 'Cusick, Matthew F.', 'Fujinami, Robert S.']",,,,
,PMC,Review: 2-mercaptoethanol alteration of in vitro immune functions of species other than murine,http://dx.doi.org/10.1016/j.jim.2013.11.007,PMC3946847,,,"Descriptions that organosulfurs could alter biologically relevant cellular functions began some 40 years ago when cell mediated and humoral murine in vitro immune responses were reported to be dramatically enhanced by any of four xenobiotic, sulfhydryl compounds—2-mercaptoethanol (2-ME), dithiothreitol, glutathione, and L-cysteine; the most effective of the four was 2-ME. These findings triggered a plethora of reports defining 2-ME benefits for a multitude of immunological processes, primarily with murine models. This led to investigations on 2-ME alterations of (a) immune functions in other species, (b) activities of other cell-types, and (c) in situ diseases. In addition, the early findings may have been instrumental in identification of the previously undefined anticarcinogenic chemicals in specific foods as organosulfurs. Outside the plant organosulfurs, there are no comprehensive reviews of these areas to help define mechanisms by which organosulfurs function as well as identify potential alternative uses. Therefore, the present review will focus on 2-ME alterations of in vitro immune functions in species other than murine; namely, fish, amphibian, reptile, avian, whales, dolphins, rat, hamster, rabbit, guinea pig, feline, canine, porcine, ovine, bovine, and human. Processes, some unique to a given species, were in general, enhanced and in some cases dependent upon the presence of 2-ME. The largest benefits occurred in media that were serum free, followed by those in autologous serum and then fetal bovine serum supplemented medium. Concentrations of 2-ME were generally in the low μM range, with exceptions of those for salamander (20 mM), turtles (70 mM) and dolphins (7 mM). The few studies designed to assess mechanisms found that changes induced by 2-ME were generally accompanied by alterations of reduced/oxidized glutathione cellular concentrations. The major benefit for most studies, however, was to increase the sensitivity of the culture environment, which permitted a specific process to be more easily dissected.",,"Click, Robert E.",,,,
,PMC,CEACAM1 loss links inflammation to Insulin Resistance in obesity and Non-alcoholic Steatohepatitis (NASH),http://dx.doi.org/10.1007/s00281-013-0407-3,PMC3946532,,,"Mounting epidemiological evidence points to an association between metabolic syndrome and non-alcoholic steatohepatitis (NASH), an increasingly recognized new epidemic. NASH pathologies include hepatocellular ballooning, lobular inflammation, hepatocellular injury, apoptosis and hepatic fibrosis. We will review the relationship between insulin resistance and inflammation in visceral obesity and NASH in an attempt to shed more light on the pathogenesis of these major metabolic diseases. Moreover, we will identify loss of the Carcinoembryonic antigen-related cell adhesion molecule 1 as a unifying mechanism linking the immunological and metabolic abnormalities in NASH.",,"['Najjar, Sonia M.', 'Russo, Lucia']",,,,
,PMC,Cell-based antiviral screening against coronaviruses: Developing virus-specific and broad-spectrum inhibitors,http://dx.doi.org/10.1016/j.antiviral.2013.11.004,PMC3931262,,,"To combat the public health threat from emerging coronaviruses (CoV), the development of antiviral therapies with either virus-specific or pan-CoV activities is necessary. An important step in antiviral drug development is the screening of potential inhibitors in cell-based systems. The recent emergence of the Middle East respiratory syndrome (MERS)-CoV necessitates adapting methods that have been used to identify antivirals against the severe, acute respiratory syndrome (SARS)-CoV and developing new approaches to more efficiently screen antiviral drugs. In this article we review cell-based assays using infectious virus (BSL-3) and surrogate assays (BSL-2) that can be implemented to accelerate antiviral development against MERS-CoV and future emergent coronaviruses. This paper forms part of a series of invited articles in Antiviral Research on “From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.”",,"['Kilianski, Andy', 'Baker, Susan C.']",,,,
,PMC,Safety and Immunogenicity of High Dose Trivalent Inactivated Influenza Vaccine in Pediatric Patients with Acute Lymphoblastic Leukemia,http://dx.doi.org/10.1002/pbc.24863,PMC4310469,,,"BACKGROUND: Although children with acute lymphoblastic leukemia (ALL) mount immune responses after vaccination with the trivalent influenza vaccine (TIV), these responses are lower compared to controls. Recently, a high dose (HD) TIV was found to increase the level of antibody response in elderly patients compared to the standard dose (SD) TIV. We hypothesized that the HD TIV would be well-tolerated and more immunogenic compared to the SD TIV in pediatric subjects with ALL. PROCEDURE: This was a randomized, double-blind, phase I safety and immunogenicity trial comparing the HD to the SD TIV in children with ALL. Subjects were randomized 2:1 to receive either the HD (60µg) or the SD (15µg) TIV. Local and systemic reactions were solicited, hemagglutinin inhibition titers to influenza virus antigens were measured, and monitoring labs were collected prior to and/or after each vaccination. RESULTS: Fifty subjects were enrolled (34 HD, 16 SD). Mean age was 8.5 years; 63% were male, and 80% were in maintenance therapy. There were no significant differences reported in local or systemic symptoms. No severe adverse events were attributed to vaccination. No significant differences between the HD and SD TIV groups were noted for immune responses. CONCLUSIONS: No differences were noted between the HD and SD TIV groups for solicited systemic and local reactions. Since this study was not powered for immunogenicity, a phase II trial is needed to determine the immunogenicity of HD versus SD TIV in the pediatric ALL population.",,"['McManus, Meghann', 'Frangoul, Haydar', 'McCullers, Jonathan A.', 'Wang, Li', ""O'Shea, Alice"", 'Halasa, Natasha']",,,,
,PMC,Evaluation of Serologic and Antigenic Relationships Between Middle Eastern Respiratory Syndrome Coronavirus and Other Coronaviruses to Develop Vaccine Platforms for the Rapid Response to Emerging Coronaviruses,http://dx.doi.org/10.1093/infdis/jit609,PMC3952667,,,"Background. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing severe acute respiratory disease and pneumonia, with 44% mortality among 136 cases to date. Design of vaccines to limit the virus spread or diagnostic tests to track newly emerging strains requires knowledge of antigenic and serologic relationships between MERS-CoV and other CoVs. Methods. Using synthetic genomics and Venezuelan equine encephalitis virus replicons (VRPs) expressing spike and nucleocapsid proteins from MERS-CoV and other human and bat CoVs, we characterize the antigenic responses (using Western blot and enzyme-linked immunosorbent assay) and serologic responses (using neutralization assays) against 2 MERS-CoV isolates in comparison with those of other human and bat CoVs. Results. Serologic and neutralization responses against the spike glycoprotein were primarily strain specific, with a very low level of cross-reactivity within or across subgroups. CoV N proteins within but not across subgroups share cross-reactive epitopes with MERS-CoV isolates. Our findings were validated using a convalescent-phase serum specimen from a patient infected with MERS-CoV (NA 01) and human antiserum against SARS-CoV, human CoV NL63, and human CoV OC43. Conclusions. Vaccine design for emerging CoVs should involve chimeric spike protein containing neutralizing epitopes from multiple virus strains across subgroups to reduce immune pathology, and a diagnostic platform should include a panel of nucleocapsid and spike proteins from phylogenetically distinct CoVs.",,"['Agnihothram, Sudhakar', 'Gopal, Robin', 'Yount, Boyd L.', 'Donaldson, Eric F.', 'Menachery, Vineet D.', 'Graham, Rachel L.', 'Scobey, Trevor D.', 'Gralinski, Lisa E.', 'Denison, Mark R.', 'Zambon, Maria', 'Baric, Ralph S.']",,,,
,PMC,Infections and Their Role in Childhood Asthma Inception,http://dx.doi.org/10.1111/pai.12147,PMC3977202,,,"The association of early onset wheezing with common viral and bacterial infections has raised significant interest in the role of infections in childhood asthma inception. This article serves to review these relationships among infections, host factors, and asthma inception in childhood.",,"['Thomas, Amy O.', 'Lemanske, Robert F.', 'Jackson, Daniel J.']",,,,
,PMC,"Pathogenesis of GIII.2 bovine norovirus, CV186-OH/00/US strain in gnotobiotic calves",http://dx.doi.org/10.1016/j.vetmic.2013.11.008,PMC3905316,,,"The pathogenesis of GIII.2 bovine norovirus (BoNoV) is not well understood. Our study demonstrated persisting diarrhea and prolonged fecal shedding, but with a lack of significant intestinal lesions in gnotobiotic (Gn) calves infected with GIII.2 BoNoV, CV186-OH/00/US strain. Nine 4 to 7-day-old Angus/Jersey crossbred Gn calves were orally inoculated with 10.0-11.9 log(10) genomic equivalents (GE)/calf of CV186-OH (n=7) or mock (n=2). Calves were euthanized at post-inoculation day (PID) 1 (n=1) when moderate to severe lethargy was observed and at PIDs 2-6 (n=4) after lethargy had subsided. Two calves were kept longer term (until PID 30) for monitoring fecal shedding patterns by TaqMan real-time RT-PCR (qRT-PCR). Most infected calves exhibited two clinical signs: i) acute but persisting diarrhea and ii) acute moderate to severe lethargy. The two infected calves, followed longer-term, had prolonged fecal viral RNA shedding [peak average titer of 11.8 (± 0.2) log(10) GE/ml] at least until PID 20. By qRT-PCR, 5 infected calves had low viral RNA titers in serum, ranging from 4.0 to 5.8 log(10) GE/ml, at PIDs 1-5, but not (<2.7 log(10) GE/ml) at PIDs 6-30. The latter observation coincided with the presence of serum IgG antibody to BoNoV at PIDs 8-30. Collectively, the GIII.2 BoNoV strain CV186-OH induced only mild enteropathogenicity, evident by the lack of significant intestinal lesions, but it led to persisting mild diarrhea and prolonged fecal virus shedding in Gn calves. The prolonged fecal shedding of GIII.2 BoNoV might partially explain how this virus is maintained as endemic infections in cattle.",,"['Jung, Kwonil', 'Scheuer, Kelly A.', 'Zhang, Zhenwen', 'Wang, Qiuhong', 'Saif, Linda J.']",,,,
,PMC,"3-Azatetracyclo[5.2.1.1(5,8).0(1,5)]undecane derivatives: from wild-type inhibitors of the M2 ion channel of influenza A virus to derivatives with potent activity against the V27A mutant",http://dx.doi.org/10.1021/jm401340p,PMC3889466,,,"We have synthesized and characterized a series of compounds containing the 3-azatetracyclo[5.2.1.1(5,8).0(1,5)]undecane scaffold designed as analogs of amantadine, an inhibitor of the M2 proton channel of influenza A virus. Inhibition of the wild-type (wt) M2 channel and the amantadine-resistant A/M2-S31N and A/M2-V27A mutant ion channels were measured in Xenopus oocytes using two-electrode voltage clamp (TEV) assays. Most of the novel compounds inhibited the wt ion channel in the low micromolar range. Of note, several compounds inhibited the A/M2 V27A mutant ion channel, one of them with submicromolar IC(50). None of the compounds was found to inhibit the S31N mutant ion channel. The antiviral activity of three novel dual wt and A/M2-V27A channels inhibitors was confirmed by influenza virus yield assays.",,"['Rey-Carrizo, Matias', 'Torres, Eva', 'Ma, Chunlong', 'Barniol-Xicota, Marta', 'Wang, Jun', 'Wu, Yibing', 'Naesens, Lieve', 'DeGrado, William F.', 'Lamb, Robert A.', 'Pinto, Lawrence H.', 'Vázquez, Santiago']",,,,
,PMC,"THE INTRACELLULAR CARGO RECEPTOR ERGIC-53 IS REQUIRED FOR THE PRODUCTION OF INFECTIOUS ARENAVIRUS, CORONAVIRUS, AND FILOVIRUS PARTICLES",http://dx.doi.org/10.1016/j.chom.2013.10.010,PMC3999090,,,"Arenaviruses and hantaviruses cause severe and often fatal diseases in humans. Little is known regarding host proteins required for their propagation. We identified human proteins that interact with the glycoproteins (GPs) of a prototypic arenavirus and hantavirus and show that the lectin ERGIC-53 - a cargo receptor required for cellular glycoprotein trafficking within the early exocytic pathway - associates with arenavirus, hantavirus, coronavirus, orthomyxovirus, and filovirus GPs. ERGIC-53 binds to arenavirus GPs through a lectin-independent mechanism, traffics to arenavirus budding sites, and is incorporated into arenavirus particles. ERGIC-53 is required for arenavirus, coronavirus, and filovirus propagation; in its absence, GP-containing virus particles form, but are noninfectious due, in part, to their inability to attach to host cells. Thus, we have identified a class of pathogen-derived ERGIC-53 ligands, a lectin-independent basis for their association with ERGIC-53, and a role for ERGIC-53 in the propagation of several highly pathogenic RNA virus families.",,"['Klaus, Joseph', 'Eisenhauer, Philip', 'Russo, Joanne', 'Mason, Anne', 'Do, Danh', 'King, Benjamin', 'Taatjes, Douglas', 'Cornillez-Ty, Cromwell', 'Boyson, Jonathan E.', 'Thali, Markus', 'Zheng, Chunlei', 'Liao, Lujian', 'Yates, John R.', 'Zhang, Bin', 'Ballif, Bryan A.', 'Botten, Jason']",,,,
,PMC,BANK1 Controls CpG-induced IL-6 Secretion Via a p38 and MNK1/2- eIF4E Translation Initiation Pathway(),http://dx.doi.org/10.4049/jimmunol.1301203,PMC3858538,,,"BANK1, an adaptor protein expressed in B-cells, plays a little understood role in B-cell signaling. Because BANK1 contains an N-terminal putative Toll-interleukin 1 receptor (TIR) domain, we used mouse Bank1(−/−) splenic B cells to test if BANK1 affects signaling induced by the TLR9 agonist CpG. Following CpG stimulation BANK1 deficiency reduced p38 phosphorylation without affecting that of ERK or JNK and reduced IL-6 secretion. Bank1(−/−) B cells showed reduced phosphorylation of MNK1/2 and eIF4E, suggesting an effect on translation initiation, while Bank1(−/−) had no effect on IL6 mRNA stability, thus suggesting that BANK1 has no effect on MK2 signaling. IL-6 secretion observed when CpG stimulation was combined with anti-CD40, was reduced in the absence of BANK1. While in the presence of anti-CD40 stimulation CpG induced a stronger phosphorylation of AKT, mTOR and 4E-BP1, Bank1(−/−) had no effect on phosphorylation of mTOR and 4E-BP1, and weakly on AKT, implying that BANK1 does not affect the release of eIF4E by phospho-4E-BP1. Together these data establish a previously unrecognized role for BANK1 in CpG-induced responses by splenic B cells on p38 signaling and control of translation initiation of IL-6 via MNK1/2 and eIF4E.",,"['Wu, Ying-Yu', 'Kumar, Ramesh', 'Haque, Mohammed Shamsul', 'Castillejo-López, Casimiro', 'Alarcón-Riquelme, Marta E.']",,,,
,PMC,Prediction of Intrinsic Disorder in MERS-CoV/HCoV-EMC Supports a High Oral-Fecal Transmission,http://dx.doi.org/10.1371/currents.outbreaks.22254b58675cdebc256dbe3c5aa6498b,PMC3828228,24270586,CC BY,"A novel coronavirus, MERS-CoV (NCoV, HCoV-EMC/2012), originating from the Middle-East, has been discovered. Incoming data reveal that the virus is highly virulent to humans. A model that categorizes coronaviuses according to the hardness of their shells was developed before the discovery of MERS-CoV. Using protein intrinsic disorder prediction, coronaviruses were categorized into three groups that can be linked to the levels of oral-fecal and respiratory transmission regardless of genetic proximity. Using this model, MERS-CoV is placed into disorder group C, which consists of coronaviruses that have relatively hard inner and outer shells. The members of this group are likely to persist in the environment for a longer period of time and possess the highest oral-fecal components but relatively low respiratory transmission components. Oral-urine and saliva transmission are also highly possible since both require harder protective shells. Results show that disorder prediction can be used as a tool that suggests clues to look for in further epidemiological investigations.",2013 Nov 13,"['Goh, Gerard Kian-Meng', 'Dunker, A. Keith', 'Uversky, Vladimir']",PLoS Curr,,,
,PMC,Second isirv antiviral group conference: overview,http://dx.doi.org/10.1111/irv.12207,PMC6499332,,,,,"['Hurt, Aeron C.', 'Ison, Michael G.', 'Hayden, Frederick G.', 'Hay, Alan J.']",,,,
,PMC,Influenza prevention and treatment in transplant recipients and immunocompromised hosts,http://dx.doi.org/10.1111/irv.12170,PMC6492654,,,"The host immune response is critical for the control and clearance of influenza virus after initial infection. Unfortunately, key components of the innate and adaptive responses to influenza are compromised in solid organ and hematopoietic stem cell transplant recipients. As a result, influenza in these key patient populations is associated with prolonged viral shedding, more frequent complications, including bacterial and fungal superinfections and rejection, and increased mortality. While vaccine is the critical prophylaxis strategy in other populations, response rates are diminished, particularly early post‐transplant, among immunocompromised patients. Prospective data suggest that antiviral prophylaxis represents an effective and safe alternative to vaccine in patients who would be predicted to have poor responses to influenza vaccine. While there have not been randomized, controlled studies of antiviral therapy completed in solid organ or hematopoietic stem cell patient populations, observational data suggest that early therapy is associated with reduced rates of progression to lower airway involvement, morbidity, and mortality. Further studies are needed to define the optimal regimen, dose, duration, and endpoint to define successful treatment.",,"Ison, Michael G.",,,,
,PMC,Adjunctive therapies and immunomodulating agents for severe influenza,http://dx.doi.org/10.1111/irv.12171,PMC6492653,,,"The value of adjunctive immunomodulatory therapies in treating severe influenza and other respiratory viral infections remains uncertain. Although often used, systemic corticosteroids may increase the risk of mortality and morbidity (e.g. secondary infections) in severe influenza and other viral infections, especially if there is delay or lack of effective antiviral therapy. Non‐randomized studies suggest that convalescent plasma appears useful as add‐on therapy for patients with severe acute respiratory syndrome, avian influenza A(H5N1), and influenza A (H1N1) 2009 pandemic [A(H1N1)pdm09), but it is limited by its availability. A recent randomized controlled trial (RCT) comparing hyperimmune globulin prepared from convalescent plasma against normal intravenous gammaglobulin (IVIG) manufactured before 2009 as control in patients with severe A(H1N1)pdm09 infection on standard antiviral treatment has shown that the hyperimmune globulin group who received treatment within 5 days of symptom onset had a lower viral load and reduced mortality compared with the controls. A number of agents with immunomodulatory effects (e.g. acute use of statins, N‐acetylcysteine, macrolides, PPAR agonists, IVIG, celecoxib, mesalazine) have been proposed for influenza management. However, more animal and detailed human observational studies and preferably RCTs controlling for the effects of antiviral therapy and disease severity are needed for evaluating these agents. The role of plasmapheresis and hemoperfusion as rescue therapy also merits more investigation.",,"['Hui, David S. C.', 'Lee, Nelson']",,,,
,PMC,Advances in antivirals for non‐influenza respiratory virus infections,http://dx.doi.org/10.1111/irv.12173,PMC6492651,,,"Progress in the development of antivirals for non‐influenza respiratory viruses has been slow with the result that many unmet medical needs and few approved agents currently exist. This commentary selectively reviews examples of where specific agents have provided promising clinical benefits in selected target populations and also considers potential therapeutics for emerging threats like the SARS and Middle East respiratory syndrome coronaviruses. Recent studies have provided encouraging results in treating respiratory syncytial virus infections in lung transplant recipients, serious parainfluenza virus and adenovirus infections in immunocompromised hosts, and rhinovirus colds in outpatient asthmatics. While additional studies are needed to confirm the efficacy and safety of the specific agents tested, these observations offer the opportunity to expand therapeutic studies to other patient populations.",,"Hayden, Frederick G.",,,,
,PMC,Viral–bacterial interactions–therapeutic implications,http://dx.doi.org/10.1111/irv.12174,PMC3831167,,,"Viral and bacterial respiratory tract infections are a leading cause of morbidity and mortality worldwide, despite the development of vaccines and potent antibiotics. Frequently, viruses and bacteria can co‐infect the same host, resulting in heightened pathology and severity of illness compared to single infections. Bacterial superinfections have been a significant cause of death during every influenza pandemic, including the 2009 H1N1 pandemic. This review will analyze the epidemiology and global impact of viral and bacterial co‐infections of the respiratory tract, with an emphasis on bacterial infections following influenza. We will next examine the mechanisms by which viral infections enhance the acquisition and severity of bacterial infections. Finally, we will discuss current management strategies for diagnosing and treating patients with suspected or confirmed viral‐bacterial infections of the respiratory tract. Further investigation into the interactions between viral and bacterial infections is necessary for developing new therapeutic approaches aimed at mitigating the severity of co‐infections.",,"Deng, Jane C.",,,,
,PMC,State of Knowledge and Data Gaps of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Humans,http://dx.doi.org/10.1371/currents.outbreaks.0bf719e352e7478f8ad85fa30127ddb8,PMC3828229,24270606,CC BY,"Background: Between September 2012 and 22 October 2013, 144 laboratory-confirmed and 17 probable MERS-CoV cases from nine countries were notified to WHO. Methods: We summarize what is known about the epidemiology, virology, phylogeny and emergence of MERS-CoV to inform public health policies. Results: The median age of patients (n=161) was 50 years (range 14 months to 94 years), 64.5% were male and 63.4% experienced severe respiratory disease. 76.0% of patients were reported to have ≥1 underlying medical condition and fatal cases, compared to recovered or asymptomatic cases were more likely to have an underlying condition (86.8% vs. 42.4%, p<0.001). Analysis of genetic sequence data suggests multiple independent introductions into human populations and modelled estimates using epidemiologic and genetic data suggest R<sub>0</sub> is <1, though the upper range of estimates may exceed 1. Index/sporadic cases (cases with no epidemiologic-link to other cases) were more likely to be older (median 59.0 years vs. 43.0 years, p<0.001) compared to secondary cases, although these proportions have declined over time. 80.9% vs. 67.2% of index/sporadic and secondary cases, respectively, reported ≥1 underlying condition. Clinical presentation ranges from asymptomatic to severe pneumonia with acute respiratory distress syndrome and multi-organ failure. Nearly all symptomatic patients presented with respiratory symptoms and 1/3 of patients also had gastrointestinal symptoms. Conclusions: Sustained human-to-human transmission of MERS-CoV has not been observed. Outbreaks have been extinguished without overly aggressive isolation and quarantine suggesting that transmission of virus may be stopped with implementation of appropriate infection control measures.",2013 Nov 12,,PLoS Curr,,,
,PMC,Analysis of synonymous codon usage in Newcastle disease virus hemagglutinin–neuraminidase (HN) gene and fusion protein (F) gene,http://dx.doi.org/10.1007/s13337-013-0175-7,PMC3889239,,,"Newcastle disease virus (NDV) hemagglutinin–neuraminidase (HN) is a multifunctional protein, which possesses both the receptor recognition and neuraminidase activities. The fusion (F) protein is a type I membrane glycoprotein that mediates the merger of the viral envelope to the host cell membrane. Although the functions of the HN and F proteins have been well studied, however, the factors shaping synonymous codon usage bias and nucleotide composition in HN and F genes have been few reported. In our study, we analyzed synonymous codon usage using the 69 NDV HN and F genes, respectively. The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in HN and F genes. In addition, other factors, such as the aromaticity and hydrophobicity, also influence the codon usage variation among HN and F genes. This study represents the most comprehensive analysis to date of NDV HN and F genes codon usage patterns and provides a basic understanding of the mechanisms for codon usage bias. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13337-013-0175-7) contains supplementary material, which is available to authorized users.",,"['Cao, Hong-wei', 'Li, De-shan', 'Zhang, Hua']",,,,
,PMC,"A One‐Step RT‐PCR Array for Detection and Differentiation of Zoonotic Influenza Viruses H5N1, H9N2, and H1N1",http://dx.doi.org/10.1002/jcla.21627,PMC6807405,,,"BACKGROUND: Rapid and comprehensive pathogen identification is crucial in zoonotic influenza diagnosis. METHODS: By optimizing the design of primers and probes and reverse‐transcriptase polymerase chain reaction (RT‐PCR) conditions, we achieved simultaneous detection of multiple influenza and zoonotic influenza viruses, including H1N1, H5N1, and H9N2 strains, in a one‐step, quantitative real‐time RT‐PCR array (rRT‐PCR array) of RNA from multiple influenza strains utilizing a single set of conditions for RT‐PCR amplification. The target sequences from all targeted zoonotic influenza viruses were cloned into recombinant RNA virus particles, which were used to evaluate sensitivity, specificity, and reproducibility of the zoonotic influenza viruses RT‐PCR array. RESULTS: The detection limit of the array was shown to be between 10(0) and 10(1) copies per reaction, and the standard curve demonstrated a linear range from 10 to 10(6) copies. Thus, the analytical sensitivity of this zoonotic influenza viruses RT‐PCR array is 10–100 times higher than conventional RT‐PCR. Specificity of the one‐step zoonotic influenza viruses RT‐PCR array was verified by comparison of results obtained with retroviral‐like particles (RVPs), which contained RNA from isolates of seasonal influenza viruses, zoonotic influenza viruses, and other pathogens known to cause acute respiratory disease. CONCLUSION: The high sensitivity, rapidity, reproducibility, and specificity of this zoonotic influenza viruses rRT‐PCR array has been verified as being sufficient to detect the presence of multiple zoonotic influenza viruses in a single assay. The zoonotic influenza viruses RT‐PCR array might provide rapid identification of emergent zoonotic influenza viruses strains during influenza outbreaks and disease surveillance initiatives.",,"['Chen, Yao', 'Liu, Tiancai', 'Cai, Lijuan', 'Du, Hongyan', 'Li, Ming']",,,,
,PMC,A decade after SARS: Strategies to control emerging coronaviruses,http://dx.doi.org/10.1038/nrmicro3143,PMC5147543,,,"Two novel coronaviruses have emerged in humans in the 21(st) century, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome human coronavirus (MERS-CoV), both of which cause acute respiratory distress syndrome (ARDS) and have high mortality rates. There are no clinically approved vaccines or antiviral drugs available for either of these infections; thus, a priority in the field is the development of effective therapeutic and preventive strategies that can be readily applied to new emergent strains. This review will: describe the emergence and identification of novel human coronaviruses over the last 10 years; review their key biological features, including tropism and receptor use; and summarize approaches to develop broadly effective vaccines.",,"['Graham, Rachel L.', 'Donaldson, Eric F.', 'Baric, Ralph S.']",,,,
,PMC,Emerging viral diseases of livestock in the developing world,http://dx.doi.org/10.1007/s13337-013-0164-x,PMC3832702,,,"Emerging and reemerging viral diseases of livestock and human beings are in sharp rise in recent years. Importantly, many of these viruses, including influenza, Hendra, Nipah and corona are of zoonotic importance. Several viral diseases of livestock such as bluetongue, peste des petits ruminants, camel pox, equine infectious anaemia, chicken anaemia and sheep-associated malignant catarrhal fever are crossing their traditional boundaries. Emergence of new serotypes and variant forms of viruses as in the case of blue tongue virus, avian infectious bronchitis virus, Newcastle disease virus adds additional level of complexity. The increased incidence of emerging and reemerging viral diseases could be attributed to several factors including deforestation and surge in direct contact of livestock and humans with wild animals and birds. This special issue of “Indian Journal of Virology” is focused on diverse aspects of above diseases: isolation and characterization of viruses, epidemiology, pathogenesis, diagnosis, prevention measures and vaccine development.",,"Bayry, Jagadeesh",,,,
,PMC,Decoding the complexity of type I interferon to treat persistent viral infections,http://dx.doi.org/10.1016/j.tim.2013.10.003,PMC3864553,,,"Type I interferons (IFN-I) are a broad family of cytokines that are central to the innate immune response. These proteins have long been appreciated for the critical roles they play in restraining viral infections and shaping antiviral immune responses. However, in recent years there has been increased awareness of the immunosuppressive actions of these proteins as well. While there are many current therapeutic applications to manipulate IFN-I pathways we have limited understanding of the mechanisms by which these therapies are actually functioning. In this review we highlight the diversity and temporal impact of IFN-I signaling, discuss the current therapeutic uses of IFN-I, and explore the strategy of blocking IFN-I to alleviate immune dysfunction in persistent virus infections.",,"['Wilson, Elizabeth B.', 'Brooks, David G.']",,,,
,PMC,Gene duplication and phylogeography of North American members of the Hart Park serogroup of avian rhabdoviruses,http://dx.doi.org/10.1016/j.virol.2013.10.024,PMC3873333,,,"Flanders virus (FLAV) and Hart Park virus (HPV) are rhabdoviruses that circulate in mosquito-bird cycles in the eastern and western United States, respectively, and constitute the only two North American representatives of the Hart Park serogroup. Previously, it was suggested that FLAV is unique among the rhabdoviruses in that it contains two pseudogenes located between the P and M genes, while the cognate sequence for HPV has been lacking. Herein, we demonstrate that FLAV and HPV do not contain pseudogenes in this region, but encode three small functional proteins designated as U1, U2, and U3 that apparently arose by gene duplication. To further investigate the U1-U2-U3 region, we conducted the first large-scale evolutionary analysis of a member of the Hart Park serogroup by analyzing over 100 spatially and temporally distinct FLAV isolates. Our phylogeographic analysis demonstrates that although FLAV appears to be slowly evolving, phylogenetically divergent lineages co-circulate sympatrically.",,"['Allison, Andrew B.', 'Mead, Daniel G.', 'Palacios, Gustavo F.', 'Tesh, Robert B.', 'Holmes, Edward C.']",,,,
,PMC,Detection Of Viral And Bacterial Pathogens In Acute Respiratory Infections,http://dx.doi.org/10.1016/j.jinf.2013.10.013,PMC3947238,,,"OBJECTIVES: The role of bacteria in acute respiratory illnesses (ARI) of adults and interactions with viral infections is incompletely understood. This study tested the hypothesis that bacterial co-infection during ARI adds to airway inflammation and illness severity. METHODS: Two groups of 97 specimens each were randomly selected from multiplex-PCR identified virus-positive and virus-negative nasal specimens obtained from adults with new onset ARI, and 40 control specimens were collected from healthy adults. All specimens were analyzed for Haemophilus influenza(HI), Moraxella catarrhalis(MC) and Streptococcus pneumonia(SP) by quantitative-PCR. General linear models tested for relationships between respiratory pathogens, biomarkers (nasal wash neutrophils and CXCL8), and ARI-severity. RESULTS: Nasal specimens from adults with ARIs were more likely to contain bacteria (37% overall; HI=28%, MC=14%, SP=7%) compared to specimens from healthy adults (5% overall; HI=0%, MC=2.5%, SP=2.5%;p<0.001). Among ARI specimens, bacteria were more likely to be detected among virus-negative specimens compared to virus-positive specimens (46% vs. 27%;p=0.0046). The presence of bacteria was significantly associated with increased CXCL8 and neutrophils, but not increased symptoms. CONCLUSION: Pathogenic bacteria were more often detected in virus-negative ARI, and also associated with increased inflammatory biomarkers. These findings suggest the possibility that bacteria may augment virus-induced ARI and contribute to airway inflammation. SUMMARY: We tested whether bacterial pathogens were associated with ARI illness and inflammation. Bacteria were detected more often in nasal secretions during ARI, especially in samples without detectable viruses, and were associated with increased airway inflammation, but not increased symptoms.",,"['Obasi, Chidi N.', 'Barrett, Bruce', 'Brown, Roger', 'Vrtis, Rose', 'Barlow, Shari', 'Muller, Daniel', 'Gern, James']",,,,
,PMC,Characterizations of particle size distribution of the droplets exhaled by sneeze,http://dx.doi.org/10.1098/rsif.2013.0560,PMC3785820,,,"This work focuses on the size distribution of sneeze droplets exhaled immediately at mouth. Twenty healthy subjects participated in the experiment and 44 sneezes were measured by using a laser particle size analyser. Two types of distributions are observed: unimodal and bimodal. For each sneeze, the droplets exhaled at different time in the sneeze duration have the same distribution characteristics with good time stability. The volume-based size distributions of sneeze droplets can be represented by a lognormal distribution function, and the relationship between the distribution parameters and the physiological characteristics of the subjects are studied by using linear regression analysis. The geometric mean of the droplet size of all the subjects is 360.1 µm for unimodal distribution and 74.4 µm for bimodal distribution with geometric standard deviations of 1.5 and 1.7, respectively. For the two peaks of the bimodal distribution, the geometric mean (the geometric standard deviation) is 386.2 µm (1.8) for peak 1 and 72.0 µm (1.5) for peak 2. The influences of the measurement method, the limitations of the instrument, the evaporation effects of the droplets, the differences of biological dynamic mechanism and characteristics between sneeze and other respiratory activities are also discussed.",,"['Han, Z. Y.', 'Weng, W. G.', 'Huang, Q. Y.']",,,,
,PMC,DNA Immunization,http://dx.doi.org/10.1002/9780471729259.mc1803s31,PMC3920301,,,"DNA immunization was discovered in early 1990s and its use has been expanded from vaccine studies to a broader range of biomedical research, such as the generation of high quality polyclonal and monoclonal antibodies as research reagents. In this unit, three common DNA immunization methods are described: needle injection, electroporation and gene gun. In addition, several common considerations related to DNA immunization are discussed.",,"['Wang, Shixia', 'Lu, Shan']",,,,
,PMC,MCPIP1 restricts HIV infection and is rapidly degraded in activated CD4+ T cells,http://dx.doi.org/10.1073/pnas.1316208110,PMC3839757,,,"HIV-1 primarily infects activated CD4+ T cells and macrophages. Quiescent CD4+ T cells, however, possess cellular factors that limit HIV-1 infection at different postentry steps of the viral life cycle. Here, we show that the previously reported immune regulator monocyte chemotactic protein-induced protein 1 (MCPIP1) restricts HIV-1 production in CD4+ T cells. While the ectopic expression of MCPIP1 in cell lines abolished the production of HIV-1, silencing of MCPIP1 enhanced HIV-1 production. Subsequent analysis indicated that MCPIP1 imposes its restriction by decreasing the steady levels of viral mRNA species through its RNase domain. Remarkably, common T-cell stimuli induced the rapid degradation of MCPIP1 in both T-cell lines and quiescent human CD4+ T cells. Lastly, blocking the proteosomal degradation of MCPIP1 by MG132 abrogated HIV-1 production in phorbol 12-myristate 13-acetate/ionomycin-stimulated human CD4+ T cells isolated from healthy donors. Overall, MCPIP1 poses a potent barrier against HIV-1 infection at a posttranscriptional stage. Although the observed HIV restriction conferred by MCPIP1 does not seem to be overcome by any viral protein, it is removed during cellular stimulation. These findings provide insights into the mechanisms of cellular activation-mediated HIV-1 production in CD4+ T cells.",,"['Liu, Shufeng', 'Qiu, Chao', 'Miao, Ruidong', 'Zhou, Jianhua', 'Lee, Aram', 'Liu, Baoming', 'Lester, Sandra N.', 'Fu, Weihui', 'Zhu, Lingyan', 'Zhang, Linxia', 'Xu, Jianqing', 'Fan, Daping', 'Li, Kui', 'Fu, Mingui', 'Wang, Tianyi']",,,,
,PMC,CXCR3 Ligands Are Associated with the Continuum of Diffuse Alveolar Damage to Chronic Lung Allograft Dysfunction,http://dx.doi.org/10.1164/rccm.201305-0861OC,PMC3863740,,,"Rationale: After lung transplantation, insults to the allograft generally result in one of four histopathologic patterns of injury: (1) acute rejection, (2) lymphocytic bronchiolitis, (3) organizing pneumonia, and (4) diffuse alveolar damage (DAD). We hypothesized that DAD, the most severe form of acute lung injury, would lead to the highest risk of chronic lung allograft dysfunction (CLAD) and that a type I immune response would mediate this process. Objectives: Determine whether DAD is associated with CLAD and explore the potential role of CXCR3/ligand biology. Methods: Transbronchial biopsies from all lung transplant recipients were reviewed. The association between the four injury patterns and subsequent outcomes were evaluated using proportional hazards models with time-dependent covariates. Bronchoalveolar lavage (BAL) concentrations of the CXCR3 ligands (CXCL9/MIG, CXCL10/IP10, and CXCL11/ITAC) were compared between allograft injury patterns and “healthy” biopsies using linear mixed-effects models. The effect of these chemokine alterations on CLAD risk was assessed using Cox models with serial BAL measurements as time-dependent covariates. Measurements and Main Results: There were 1,585 biopsies from 441 recipients with 62 episodes of DAD. An episode of DAD was associated with increased risk of CLAD (hazard ratio, 3.0; 95% confidence interval, 1.9–4.7) and death (hazard ratio, 2.3; 95% confidence interval, 1.7–3.0). There were marked elevations in BAL CXCR3 ligand concentrations during DAD. Furthermore, prolonged elevation of these chemokines in serial BAL fluid measurements predicted the development of CLAD. Conclusions: DAD is associated with marked increases in the risk of CLAD and death after lung transplantation. This association may be mediated in part by an aberrant type I immune response involving CXCR3/ligands.",,"['Shino, Michael Y.', 'Weigt, S. Samuel', 'Li, Ning', 'Palchevskiy, Vyacheslav', 'Derhovanessian, Ariss', 'Saggar, Rajan', 'Sayah, David M.', 'Gregson, Aric L.', 'Fishbein, Michael C.', 'Ardehali, Abbas', 'Ross, David J.', 'Lynch, Joseph P.', 'Elashoff, Robert M.', 'Belperio, John A.']",,,,
,PMC,"Thioredoxins, Glutaredoxins, and Peroxiredoxins—Molecular Mechanisms and Health Significance: from Cofactors to Antioxidants to Redox Signaling",http://dx.doi.org/10.1089/ars.2012.4599,PMC3797455,,,"Thioredoxins (Trxs), glutaredoxins (Grxs), and peroxiredoxins (Prxs) have been characterized as electron donors, guards of the intracellular redox state, and “antioxidants”. Today, these redox catalysts are increasingly recognized for their specific role in redox signaling. The number of publications published on the functions of these proteins continues to increase exponentially. The field is experiencing an exciting transformation, from looking at a general redox homeostasis and the pathological oxidative stress model to realizing redox changes as a part of localized, rapid, specific, and reversible redox-regulated signaling events. This review summarizes the almost 50 years of research on these proteins, focusing primarily on data from vertebrates and mammals. The role of Trx fold proteins in redox signaling is discussed by looking at reaction mechanisms, reversible oxidative post-translational modifications of proteins, and characterized interaction partners. On the basis of this analysis, the specific regulatory functions are exemplified for the cellular processes of apoptosis, proliferation, and iron metabolism. The importance of Trxs, Grxs, and Prxs for human health is addressed in the second part of this review, that is, their potential impact and functions in different cell types, tissues, and various pathological conditions. Antioxid. Redox Signal. 19, 1539–1605.",,"['Hanschmann, Eva-Maria', 'Godoy, José Rodrigo', 'Berndt, Carsten', 'Hudemann, Christoph', 'Lillig, Christopher Horst']",,,,
,PMC,Public Health Watch,http://dx.doi.org/10.1177/1715163513508739,PMC3819970,,,,,"Lynas, Kathie",,,,
,PMC,The Natural History of Influenza Infection in the Severely Immunocompromised vs Nonimmunocompromised Hosts,http://dx.doi.org/10.1093/cid/cit725,PMC3871797,,,"Introduction. Medical advances have led to an increase in the world's population of immunosuppressed individuals. The most severely immunocompromised patients are those who have been diagnosed with a hematologic malignancy, solid organ tumor, or who have other conditions that require immunosuppressive therapies and/or solid organ or stem cell transplants. Materials and methods. Medically attended patients with a positive clinical diagnosis of influenza were recruited prospectively and clinically evaluated. Nasal washes and serum were collected. Evaluation of viral shedding, nasal and serum cytokines, clinical illness, and clinical outcomes were performed to compare severely immunocompromised individuals to nonimmunocompromised individuals with influenza infection. Results. Immunocompromised patients with influenza had more severe disease/complications, longer viral shedding, and more antiviral resistance while demonstrating less clinical symptoms and signs on clinical assessment. Conclusions. Immunocompromised patients are at risk for more severe or complicated influenza induced disease, which may be difficult to prevent with existing vaccines and antiviral treatments. Specific issues to consider when managing a severely immunocompromised host include the development of asymptomatic shedding, multi-drug resistance during prolonged antiviral therapy, and the potential high risk of pulmonary involvement. Clinical trials registration, ClinicalTrials.gov identifier NCT00533182.",,"['Memoli, Matthew J.', 'Athota, Rani', 'Reed, Susan', 'Czajkowski, Lindsay', 'Bristol, Tyler', 'Proudfoot, Kathleen', 'Hagey, Rachel', 'Voell, Jocelyn', 'Fiorentino, Charles', 'Ademposi, Angela', 'Shoham, Shmuel', 'Taubenberger, Jeffery K.']",,,,
,PMC,Lessons learned from case fatality risk estimates of 2009 pandemic influenza,http://dx.doi.org/10.1097/01.ede.0000434434.52506.bc,PMC3927950,,,,,"['Chowell, Gerardo', 'Viboud, Cécile']",,,,
,PMC,Relating Phylogenetic Trees to Transmission Trees of Infectious Disease Outbreaks,http://dx.doi.org/10.1534/genetics.113.154856,PMC3813836,,,"Transmission events are the fundamental building blocks of the dynamics of any infectious disease. Much about the epidemiology of a disease can be learned when these individual transmission events are known or can be estimated. Such estimations are difficult and generally feasible only when detailed epidemiological data are available. The genealogy estimated from genetic sequences of sampled pathogens is another rich source of information on transmission history. Optimal inference of transmission events calls for the combination of genetic data and epidemiological data into one joint analysis. A key difficulty is that the transmission tree, which describes the transmission events between infected hosts, differs from the phylogenetic tree, which describes the ancestral relationships between pathogens sampled from these hosts. The trees differ both in timing of the internal nodes and in topology. These differences become more pronounced when a higher fraction of infected hosts is sampled. We show how the phylogenetic tree of sampled pathogens is related to the transmission tree of an outbreak of an infectious disease, by the within-host dynamics of pathogens. We provide a statistical framework to infer key epidemiological and mutational parameters by simultaneously estimating the phylogenetic tree and the transmission tree. We test the approach using simulations and illustrate its use on an outbreak of foot-and-mouth disease. The approach unifies existing methods in the emerging field of phylodynamics with transmission tree reconstruction methods that are used in infectious disease epidemiology.",,"['Ypma, Rolf J. F.', 'van Ballegooijen, W. Marijn', 'Wallinga, Jacco']",,,,
,PMC,"T cell ageing: Effects of age on development, survival & function",,PMC3928693,24434315,CC BY-NC-SA,"Age associated decline of the immune system continues to be a major health concern. All components of innate and adaptive immunity are adversely affected to lesser or greater extent by ageing resulting in an overall decline of immunocompetence. As a result in the aged population, there is increased susceptibility to infection, poor responses to vaccination, and increased incidence of autoreactivity. There is an increasing focus on the role of T cells during ageing because of their impact on the overall immune responses. A steady decline in the production of fresh naïve T cells, more restricted T cell receptor (TCR) repertoire and weak activation of T cells are some of the effects of ageing. In this review we summarize our present understanding of the effects of ageing on naïve CD4 T cells and potential approaches for therapeutic interventions to restore protective immunity in the aged population.",2013 Nov,"['Salam, Nasir', 'Rane, Sanket', 'Das, Rituparna', 'Faulkner, Matthew', 'Gund, Rupali', 'Kandpal, Usha', 'Lewis, Virginia', 'Mattoo, Hamid', 'Prabhu, Savit', 'Ranganathan, Vidya', 'Durdik, Jeannine', 'George, Anna', 'Rath, Satyajit', 'Bal, Vineeta']",Indian J Med Res,,,
,PMC,Middle East Respiratory Syndrome (MERS) – An update,,PMC3921066,,,,,,,,,
,PMC,Effect of Spectral Transmittance through Red-Tinted Rodent Cages on Circadian Metabolism and Physiology in Nude Rats,,PMC3838609,,,"Light entrains normal circadian rhythms of physiology and metabolism in all mammals. Previous studies from our laboratory demonstrated that spectral transmittance (color) of light passing through cages affects these responses in rats. Here, we addressed the hypothesis that red tint alters the circadian nocturnal melatonin signal and circadian oscillation of other metabolic and physiologic functions. Female nude rats (Hsd:RH-Foxn1(rnu); n = 12 per group) were maintained on a 12:12-h light (300 lx; 123.0 μW/cm(2); lights on 0600):dark regimen in standard polycarbonate translucent clear or red-tinted cages. After 1 wk, rats underwent 6 low-volume blood draws via cardiocentesis over a 4-wk period. Plasma melatonin levels were low during the light phase (1.0 ± 0.2 pg/mL) in rats in both types of cages but were significantly lower in red-tinted (105.0 ± 2.4 pg/mL) compared with clear (154.8 ± 3.8 pg/mL) cages during the dark. Normal circadian rhythm of plasma total fatty acid was identical between groups. Although phase relationships of circadian rhythms in glucose, lactic acid, pO(2), and pCO(2) were identical between groups, the levels of these analytes were lower in rats in red-tinted compared with clear cages. Circadian rhythms of plasma corticosterone, insulin, and leptin were altered in terms of phasing, amplitude, and duration in rats in red-tinted compared with clear cages. These findings indicate that spectral transmittance through red-colored cages significantly affects circadian regulation of neuroendocrine, metabolic, and physiologic parameters, potentially influencing both laboratory animal health and wellbeing and scientific outcomes.",,"['Dauchy, Robert T', 'Wren, Melissa A', 'Dauchy, Erin M', 'Hanifin, John P', 'Jablonski, Michael R', 'Warfield, Benjamin', 'Brainard, George C', 'Hill, Steven M', 'Mao, Lulu', 'Dupepe, Lynell M', 'Ooms, Tara G', 'Blask, David E']",,,,
,PMC,Apelin is a positive regulator of ACE2 in failing hearts,http://dx.doi.org/10.1172/JCI69608,PMC3859384,,,"Angiotensin converting enzyme 2 (ACE2) is a negative regulator of the renin-angiotensin system (RAS), catalyzing the conversion of Angiotensin II to Angiotensin 1-7. Apelin is a second catalytic substrate for ACE2 and functions as an inotropic and cardioprotective peptide. While an antagonistic relationship between the RAS and apelin has been proposed, such functional interplay remains elusive. Here we found that ACE2 was downregulated in apelin-deficient mice. Pharmacological or genetic inhibition of angiotensin II type 1 receptor (AT1R) rescued the impaired contractility and hypertrophy of apelin mutant mice, which was accompanied by restored ACE2 levels. Importantly, treatment with angiotensin 1-7 rescued hypertrophy and heart dysfunctions of apelin-knockout mice. Moreover, apelin, via activation of its receptor, APJ, increased ACE2 promoter activity in vitro and upregulated ACE2 expression in failing hearts in vivo. Apelin treatment also increased cardiac contractility and ACE2 levels in AT1R-deficient mice. These data demonstrate that ACE2 couples the RAS to the apelin system, adding a conceptual framework for the apelin-ACE2–angiotensin 1-7 axis as a therapeutic target for cardiovascular diseases.",,"['Sato, Teruki', 'Suzuki, Takashi', 'Watanabe, Hiroyuki', 'Kadowaki, Ayumi', 'Fukamizu, Akiyoshi', 'Liu, Peter P.', 'Kimura, Akinori', 'Ito, Hiroshi', 'Penninger, Josef M.', 'Imai, Yumiko', 'Kuba, Keiji']",,,,
,PMC,Middle East Respiratory Syndrome Coronavirus Accessory Protein 4a Is a Type I Interferon Antagonist,http://dx.doi.org/10.1128/JVI.01845-13,PMC3807936,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory infection with as yet unclear epidemiology. We previously showed that MERS-CoV counteracts parts of the innate immune response in human bronchiolar cells. Here we analyzed accessory proteins 3, 4a, 4b, and 5 for their abilities to inhibit the type I interferon response. Accessory protein 4a was found to block interferon induction at the level of melanoma differentiation-associated protein 5 (MDA5) activation presumably by direct interaction with double-stranded RNA.",,"['Niemeyer, Daniela', 'Zillinger, Thomas', 'Muth, Doreen', 'Zielecki, Florian', 'Horvath, Gabor', 'Suliman, Tasnim', 'Barchet, Winfried', 'Weber, Friedemann', 'Drosten, Christian', 'Müller, Marcel A.']",,,,
,PMC,Human Astrocytic Cells Support Persistent Coxsackievirus B3 Infection,http://dx.doi.org/10.1128/JVI.02090-13,PMC3807905,,,"Enteroviruses can frequently target the human central nervous system to induce a variety of neurological diseases. Although enteroviruses are highly cytolytic, emerging evidence has shown that these viruses can establish persistent infections both in vivo and in vitro. Here, we investigated the susceptibility of three human brain cell lines, CCF-STTG1, T98G, and SK-N-SH, to infection with three enterovirus serotypes: coxsackievirus B3 (CVB3), enterovirus 71, and coxsackievirus A9. Persistent infection was observed in CVB3-infected CCF-STTG1 cells, as evidenced by prolonged detection of infectious virions, viral RNA, and viral antigens. Of note, infected CCF-STTG1 cells expressed the nonfunctional canonical viral receptors coxsackievirus-adenovirus receptor and decay-accelerating factor, while removal of cell surface chondroitin sulfate from CCF-STTG1 cells inhibited the replication of CVB3, suggesting that receptor usage was one of the major limiting factors in CVB3 persistence. In addition, CVB3 curtailed the induction of beta interferon in infected CCF-STTG1 cells, which likely contributed to the initiation of persistence. Furthermore, proinflammatory chemokines and cytokines, such as vascular cell adhesion molecule 1, interleukin-8 (IL-8), and IL-6, were upregulated in CVB3-infected CCF-STTG1 cells and human progenitor-derived astrocytes. Our data together demonstrate the potential of CCF-STTG1 cells to be a novel cell model for studying CVB3-central nervous system interactions, providing the basis toward a better understanding of CVB3-induced chronic neuropathogenesis.",,"['Zhang, Xiaowei', 'Zheng, Zhenhua', 'Shu, Bo', 'Liu, Xijuan', 'Zhang, Zhenfeng', 'Liu, Yan', 'Bai, Bingke', 'Hu, Qinxue', 'Mao, Panyong', 'Wang, Hanzhong']",,,,
,PMC,Dynamic Viral Dissemination in Mice Infected with Yellow Fever Virus Strain 17D,http://dx.doi.org/10.1128/JVI.02149-13,PMC3807901,,,"Arboviruses such as yellow fever virus (YFV) are transmitted between arthropod vectors and vertebrate hosts. While barriers limiting arbovirus population diversity have been observed in mosquitoes, whether barriers exist in vertebrate hosts is unclear. To investigate whether arboviruses encounter bottlenecks during dissemination in the vertebrate host, we infected immunocompetent mice and immune-deficient mice lacking alpha/beta interferon (IFN-α/β) receptors (IFNAR(−/−) mice) with a pool of genetically marked viruses to evaluate dissemination and host barriers. We used the live attenuated vaccine strain YFV-17D, which contains many mutations compared with virulent YFV. We found that intramuscularly injected immunocompetent mice did not develop disease and that viral dissemination was restricted. Conversely, 32% of intramuscularly injected IFNAR(−/−) mice developed disease. By following the genetically marked viruses over time, we found broad dissemination in IFNAR(−/−) mice followed by clearance. The patterns of viral dissemination were similar in mice that developed disease and mice that did not develop disease. Unlike our previous results with poliovirus, these results suggest that YFV-17D encounters no major barriers during dissemination within a vertebrate host in the absence of the type I IFN response.",,"['Erickson, Andrea K.', 'Pfeiffer, Julie K.']",,,,
,PMC,The Perils of Pathogen Discovery: Origin of a Novel Parvovirus-Like Hybrid Genome Traced to Nucleic Acid Extraction Spin Columns,http://dx.doi.org/10.1128/JVI.02323-13,PMC3807889,,,"Next-generation sequencing was used for discovery and de novo assembly of a novel, highly divergent DNA virus at the interface between the Parvoviridae and Circoviridae. The virus, provisionally named parvovirus-like hybrid virus (PHV), is nearly identical by sequence to another DNA virus, NIH-CQV, previously detected in Chinese patients with seronegative (non-A-E) hepatitis. Although we initially detected PHV in a wide range of clinical samples, with all strains sharing ∼99% nucleotide and amino acid identity with each other and with NIH-CQV, the exact origin of the virus was eventually traced to contaminated silica-binding spin columns used for nucleic acid extraction. Definitive confirmation of the origin of PHV, and presumably NIH-CQV, was obtained by in-depth analyses of water eluted through contaminated spin columns. Analysis of environmental metagenome libraries detected PHV sequences in coastal marine waters of North America, suggesting that a potential association between PHV and diatoms (algae) that generate the silica matrix used in the spin columns may have resulted in inadvertent viral contamination during manufacture. The confirmation of PHV/NIH-CQV as laboratory reagent contaminants and not bona fide infectious agents of humans underscores the rigorous approach needed to establish the validity of new viral genomes discovered by next-generation sequencing.",,"['Naccache, Samia N.', 'Greninger, Alexander L.', 'Lee, Deanna', 'Coffey, Lark L.', 'Phan, Tung', 'Rein-Weston, Annie', 'Aronsohn, Andrew', 'Hackett, John', 'Delwart, Eric L.', 'Chiu, Charles Y.']",,,,
,PMC,Assessing Activity and Inhibition of Middle East Respiratory Syndrome Coronavirus Papain-Like and 3C-Like Proteases Using Luciferase-Based Biosensors,http://dx.doi.org/10.1128/JVI.02105-13,PMC3807373,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with an outbreak of more than 90 cases of severe pneumonia with high mortality (greater than 50%). To date, there are no antiviral drugs or specific therapies to treat MERS-CoV. To rapidly identify potential inhibitors of MERS-CoV replication, we expressed the papain-like protease (PLpro) and the 3-chymotrypsin-like protease (3CLpro) from MERS-CoV and developed luciferase-based biosensors to monitor protease activity in cells. We show that the expressed MERS-CoV PLpro recognizes and processes the canonical CoV-PLpro cleavage site RLKGG in the biosensor. However, existing CoV PLpro inhibitors were unable to block MERS-CoV PLpro activity, likely due to the divergence of the amino acid sequence in the drug binding site. To investigate MERS-CoV 3CLpro activity, we expressed the protease in context with flanking nonstructural protein 4 (nsp4) and the amino-terminal portion of nsp6 and detected processing of the luciferase-based biosensors containing the canonical 3CLpro cleavage site VRLQS. Importantly, we found that a small-molecule inhibitor that blocks replication of severe acute respiratory syndrome (SARS) CoV and murine CoV also inhibits the activity of MERS-CoV 3CLpro. Overall, the protease expression and biosensor assays developed here allow for rapid evaluation of viral protease activity and the identification of protease inhibitors. These biosensor assays can now be used to screen for MERS-CoV-specific or broad-spectrum coronavirus PLpro and 3CLpro inhibitors.",,"['Kilianski, Andy', 'Mielech, Anna M.', 'Deng, Xufang', 'Baker, Susan C.']",,,,
,PMC,Identification of a Receptor-Binding Domain in the S Protein of the Novel Human Coronavirus Middle East Respiratory Syndrome Coronavirus as an Essential Target for Vaccine Development,http://dx.doi.org/10.1128/JVI.02357-13,PMC3807362,,,,,"['Du, Lanying', 'Zhao, Guangyu', 'Kou, Zhihua', 'Ma, Cuiqing', 'Sun, Shihui', 'Poon, Vincent K. M.', 'Lu, Lu', 'Wang, Lili', 'Debnath, Asim K.', 'Zheng, Bo-Jian', 'Zhou, Yusen', 'Jiang, Shibo']",,,,
,PMC,Herpes Simplex Virus 1 Ubiquitin-Specific Protease UL36 Inhibits Beta Interferon Production by Deubiquitinating TRAF3,http://dx.doi.org/10.1128/JVI.01211-13,PMC3807349,,,"Interferon (IFN)-mediated innate immune defense is a potent antiviral mechanism. Viruses evade innate immunity and limit secretion of beta interferon (IFN-β) to replicate and survive in the host. The largest tegument protein of herpes simplex virus 1 (HSV-1), UL36, contains a novel deubiquitinase (DUB) motif embedded in its N terminus, denoted UL36 ubiquitin-specific protease (UL36USP). In the present study, we demonstrate that HSV-1 UL36USP inhibits Sendai virus (SeV)-induced interferon regulatory factor 3 (IRF3) dimerization, promoter activation, and transcription of IFN-β. The DUB activity of UL36USP is essential to block IFN-β production. UL36USP also inhibited IFN-β promoter activity induced by overexpression of the N terminus of RIG-I (RIG-IN) and MAVS, but not TBK-1, IκB kinase ε (IKKε), and IRF3/5D. UL36USP was subsequently shown to deubiquitinate TRAF3 and prevent the recruitment of the downstream adaptor TBK1. The recombinant HSV-1 lacking UL36USP DUB activity was generated. Cells infected with the mutant virus produced more IFN-β than wild-type (WT) HSV-1-infected cells. These findings demonstrate HSV-1 UL36USP removes polyubiquitin chains on TRAF3 and counteracts the IFN-β pathway.",,"['Wang, Shuai', 'Wang, Kezhen', 'Li, Jie', 'Zheng, Chunfu']",,,,
,PMC,TMPRSS2 Is an Activating Protease for Respiratory Parainfluenza Viruses,http://dx.doi.org/10.1128/JVI.01490-13,PMC3807344,,,"Here, we show that human parainfluenza viruses and Sendai virus (SeV), like other respiratory viruses, use TMPRSS2 for their activation. The membrane fusion proteins of respiratory viruses often possess serine and glutamine residues at the P2 and P3 positions, respectively, but these residues were not critical for cleavage by TMPRSS2. However, mutations of these residues affected SeV growth in specific epithelial cell lines, suggesting the importance of these residues for SeV replication in epithelia.",,"['Abe, Masako', 'Tahara, Maino', 'Sakai, Kouji', 'Yamaguchi, Hiromi', 'Kanou, Kazuhiko', 'Shirato, Kazuya', 'Kawase, Miyuki', 'Noda, Masahiro', 'Kimura, Hirokazu', 'Matsuyama, Shutoku', 'Fukuhara, Hideo', 'Mizuta, Katsumi', 'Maenaka, Katsumi', 'Ami, Yasushi', 'Esumi, Mariko', 'Kato, Atsushi', 'Takeda, Makoto']",,,,
,PMC,Role of DC-SIGN in Lassa Virus Entry into Human Dendritic Cells,http://dx.doi.org/10.1128/JVI.01893-13,PMC3807329,,,"The arenavirus Lassa virus (LASV) causes a severe hemorrhagic fever with high mortality in humans. Antigen-presenting cells, in particular dendritic cells (DCs), are early and preferred targets of LASV, and their productive infection contributes to the virus-induced immunosuppression observed in fatal disease. Here, we characterized the role of the C-type lectin DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) in LASV entry into primary human DCs using a chimera of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) expressing the LASV glycoprotein (rLCMV-LASVGP). We found that differentiation of human primary monocytes into DCs enhanced virus attachment and entry, concomitant with the upregulation of DC-SIGN. LASV and rLCMV-LASVGP bound to DC-SIGN via mannose sugars located on the N-terminal GP1 subunit of LASVGP. We provide evidence that DC-SIGN serves as an attachment factor for rLCMV-LASVGP in monocyte-derived immature dendritic cells (MDDC) and can accelerate the capture of free virus. However, in contrast to the phlebovirus Uukuniemi virus (UUKV), which uses DC-SIGN as an authentic entry receptor, productive infection with rLCMV-LASVGP was less dependent on DC-SIGN. In contrast to the DC-SIGN-mediated cell entry of UUKV, entry of rLCMV-LASVGP in MDDC was remarkably slow and depended on actin, indicating the use of different endocytotic pathways. In sum, our data reveal that DC-SIGN can facilitate cell entry of LASV in human MDDC but that its role seems distinct from the function as an authentic entry receptor reported for phleboviruses.",,"['Goncalves, Ana-Rita', 'Moraz, Marie-Laurence', 'Pasquato, Antonella', 'Helenius, Ari', 'Lozach, Pierre-Yves', 'Kunz, Stefan']",,,,
,PMC,Pattern Recognition Receptor MDA5 Modulates CD8(+) T Cell-Dependent Clearance of West Nile Virus from the Central Nervous System,http://dx.doi.org/10.1128/JVI.01403-13,PMC3807324,,,"Many viruses induce type I interferon responses by activating cytoplasmic RNA sensors, including the RIG-I-like receptors (RLRs). Although two members of the RLR family, RIG-I and MDA5, have been implicated in host control of virus infection, the relative role of each RLR in restricting pathogenesis in vivo remains unclear. Recent studies have demonstrated that MAVS, the adaptor central to RLR signaling, is required to trigger innate immune defenses and program adaptive immune responses, which together restrict West Nile virus (WNV) infection in vivo. In this study, we examined the specific contribution of MDA5 in controlling WNV in animals. MDA5(−/−) mice exhibited enhanced susceptibility, as characterized by reduced survival and elevated viral burden in the central nervous system (CNS) at late times after infection, even though small effects on systemic type I interferon response or viral replication were observed in peripheral tissues. Intracranial inoculation studies and infection experiments with primary neurons ex vivo revealed that an absence of MDA5 did not impact viral infection in neurons directly. Rather, subtle defects were observed in CNS-specific CD8(+) T cells in MDA5(−/−) mice. Adoptive transfer into recipient MDA5(+/+) mice established that a non-cell-autonomous deficiency of MDA5 was associated with functional defects in CD8(+) T cells, which resulted in a failure to clear WNV efficiently from CNS tissues. Our studies suggest that MDA5 in the immune priming environment shapes optimal CD8(+) T cell activation and subsequent clearance of WNV from the CNS.",,"['Lazear, Helen M.', 'Pinto, Amelia K.', 'Ramos, Hilario J.', 'Vick, Sarah C.', 'Shrestha, Bimmi', 'Suthar, Mehul S.', 'Gale, Michael', 'Diamond, Michael S.']",,,,
,PMC,Middle East Respiratory Syndrome Coronavirus Spike Protein Delivered by Modified Vaccinia Virus Ankara Efficiently Induces Virus-Neutralizing Antibodies,http://dx.doi.org/10.1128/JVI.01672-13,PMC3807317,,,"Middle East respiratory syndrome coronavirus (MERS-CoV) has recently emerged as a causative agent of severe respiratory disease in humans. Here, we constructed recombinant modified vaccinia virus Ankara (MVA) expressing full-length MERS-CoV spike (S) protein (MVA-MERS-S). The genetic stability and growth characteristics of MVA-MERS-S make it a suitable candidate vaccine for clinical testing. Vaccinated mice produced high levels of serum antibodies neutralizing MERS-CoV. Thus, MVA-MERS-S may serve for further development of an emergency vaccine against MERS-CoV.",,"['Song, Fei', 'Fux, Robert', 'Provacia, Lisette B.', 'Volz, Asisa', 'Eickmann, Markus', 'Becker, Stephan', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.', 'Sutter, Gerd']",,,,
,PMC,Transmissible Gastroenteritis Coronavirus Genome Packaging Signal Is Located at the 5′ End of the Genome and Promotes Viral RNA Incorporation into Virions in a Replication-Independent Process,http://dx.doi.org/10.1128/JVI.01836-13,PMC3807314,,,"Preferential RNA packaging in coronaviruses involves the recognition of viral genomic RNA, a crucial process for viral particle morphogenesis mediated by RNA-specific sequences, known as packaging signals. An essential packaging signal component of transmissible gastroenteritis coronavirus (TGEV) has been further delimited to the first 598 nucleotides (nt) from the 5′ end of its RNA genome, by using recombinant viruses transcribing subgenomic mRNA that included potential packaging signals. The integrity of the entire sequence domain was necessary because deletion of any of the five structural motifs defined within this region abrogated specific packaging of this viral RNA. One of these RNA motifs was the stem-loop SL5, a highly conserved motif in coronaviruses located at nucleotide positions 106 to 136. Partial deletion or point mutations within this motif also abrogated packaging. Using TGEV-derived defective minigenomes replicated in trans by a helper virus, we have shown that TGEV RNA packaging is a replication-independent process. Furthermore, the last 494 nt of the genomic 3′ end were not essential for packaging, although this region increased packaging efficiency. TGEV RNA sequences identified as necessary for viral genome packaging were not sufficient to direct packaging of a heterologous sequence derived from the green fluorescent protein gene. These results indicated that TGEV genome packaging is a complex process involving many factors in addition to the identified RNA packaging signal. The identification of well-defined RNA motifs within the TGEV RNA genome that are essential for packaging will be useful for designing packaging-deficient biosafe coronavirus-derived vectors and providing new targets for antiviral therapies.",,"['Morales, Lucia', 'Mateos-Gomez, Pedro A.', 'Capiscol, Carmen', 'del Palacio, Lorena', 'Enjuanes, Luis', 'Sola, Isabel']",,,,
,PMC,Apnea in Children Hospitalized With Bronchiolitis,http://dx.doi.org/10.1542/peds.2013-1501,PMC3813402,,,"OBJECTIVE: To identify risk factors for inpatient apnea among children hospitalized with bronchiolitis. METHODS: We enrolled 2207 children, aged <2 years, hospitalized with bronchiolitis at 16 sites during the winters of 2007 to 2010. Nasopharyngeal aspirates (NPAs) were obtained on all subjects, and real-time polymerase chain reaction was used to test NPA samples for 16 viruses. Inpatient apnea was ascertained by daily chart review, with outcome data in 2156 children (98%). Age was corrected for birth <37 weeks. Multivariable logistic regression was performed to identify independent risk factors for inpatient apnea. RESULTS: Inpatient apnea was identified in 108 children (5%, 95% confidence interval [CI] 4%–6%). Statistically significant, independent predictors of inpatient apnea included: corrected ages of <2 weeks (odds ratio [OR] 9.67) and 2 to 8 weeks (OR 4.72), compared with age ≥6 months; birth weight <2.3 kg (5 pounds; OR 2.15), compared with ≥3.2 kg (7 pounds); caretaker report of previous apnea during this bronchiolitis episode (OR 3.63); preadmission respiratory rates of <30 (OR 4.05), 30 to 39 (OR 2.35) and >70 (OR 2.26), compared with 40 to 49; and having a preadmission room air oxygen saturation <90% (OR 1.60). Apnea risk was similar across the major viral pathogens. CONCLUSIONS: In this prospective, multicenter study of children hospitalized with bronchiolitis, inpatient apnea was associated with younger corrected age, lower birth weight, history of apnea, and preadmission clinical factors including low or high respiratory rates and low room air oxygen saturation. Several bronchiolitis pathogens were associated with apnea, with similar apnea risk across the major viral pathogens.",,"['Schroeder, Alan R.', 'Mansbach, Jonathan M.', 'Stevenson, Michelle', 'Macias, Charles G.', 'Fisher, Erin Stucky', 'Barcega, Besh', 'Sullivan, Ashley F.', 'Espinola, Janice A.', 'Piedra, Pedro A.', 'Camargo, Carlos A.']",,,,
,PMC,Virus-induced double-membrane vesicles,http://dx.doi.org/10.4161/auto.4782,PMC5640787,,,"Many viruses that replicate in the cytoplasm compartmentalise their genome replication and transcription in specific subcellular microenvironments or organelle-like structures, to increase replication efficiency and protect against host cell defences. Recent studies have investigated the complex membrane rearrangements induced by diverse positive-strand RNA viruses, which are of two morphotypes: membrane invagination towards the lumen of the endoplasmic reticulum (ER) or other specifically targeted organelles and double-membrane vesicles (DMVs) formed by extrusion of the ER membrane. DMVs resemble small autophagosomes and the viruses inducing these intriguing organelles are known to promote autophagy, suggesting a potential link between DMVs and the autophagic pathway. In this review, we summarise recent findings concerning the biogenesis, architecture and role of DMVs in the life cycle of viruses from different families, and discuss their possible connection to autophagy or other related pathways.",,"['Blanchard, Emmanuelle', 'Roingeard, Philippe']",,,,
,PMC,Single-Dose Replication-Defective VSV-based Nipah Virus Vaccines Provide Protection from Lethal Challenge in Syrian Hamsters,http://dx.doi.org/10.1016/j.antiviral.2013.10.012,PMC3874889,,,Nipah virus (NiV) continues to cause outbreaks of fatal human encephalitis due to spillover from its bat reservoir. We determined that a single dose of replication-defective vesicular stomatitis virus (VSV)-based vaccine vectors expressing either the NiV fusion (F) or attachment (G) glycoproteins protected hamsters from over 1000 times LD(50) NiV challenge. This highly effective single-dose protection coupled with an enhanced safety profile makes these candidates ideal for potential use in livestock and humans.,,"['Lo, Michael K.', 'Bird, Brian H.', 'Chattopadhyay, Anasuya', 'Drew, Clifton P.', 'Martin, Brock E.', 'Coleman, Joann D.', 'Rose, John K.', 'Nichol, Stuart T.', 'Spiropoulou, Christina F.']",,,,
,PMC,"Utilization of human DC-SIGN and L-SIGN for entry and infection of host cells by the New World arenavirus, Junín virus",http://dx.doi.org/10.1016/j.bbrc.2013.10.106,PMC4096786,,,"The target cell tropism of enveloped viruses is regulated by interactions between viral proteins and cellular receptors determining susceptibility at a host cell, tissue or species level. However, a number of additional cell-surface moieties can also bind viral envelope glycoproteins and could act as capture receptors, serving as attachment factors to concentrate virus particles on the cell surface, or to disseminate the virus infection to target organs or susceptible cells within the host. Here, we used Junín virus (JUNV) or JUNV glycoprotein complex (GPC)-pseudotyped particles to study their ability to be internalized by the human C-type lectins hDC- or hL-SIGN. Our results provide evidence that hDC- and hL-SIGN can mediate the entry of Junín virus into cells, and may play an important role in virus infection and dissemination in the host.",,"['Martinez, M. Guadalupe', 'Bialecki, Michele A.', 'Belouzard, Sandrine', 'Cordo, Sandra M.', 'Candurra, Nélida A.', 'Whittaker, Gary R.']",,,,
,PMC,Interferon lambda 4 signals via the IFNλ receptor to regulate antiviral activity against HCV and coronaviruses,http://dx.doi.org/10.1038/emboj.2013.232,PMC3844954,,,"The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNλ4 ORF. The expression of IFNλ4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNλ4, which signals through the IFNλR1 and IL-10R2 receptor chains. Recombinant IFNλ4 is antiviral against both HCV and coronaviruses at levels comparable to IFNλ3. However, the secretion of IFNλ4 is impaired compared to that of IFNλ3, and this impairment is not due to a weak signal peptide, which was previously believed. We found that IFNλ4 gets N-linked glycosylated and that this glycosylation is required for secretion. Nevertheless, this glycosylation is not required for activity. Together, these findings result in the paradox that IFNλ4 is strongly antiviral but a disadvantage during HCV infection.",,"['Hamming, Ole J', 'Terczyńska-Dyla, Ewa', 'Vieyres, Gabrielle', 'Dijkman, Ronald', 'Jørgensen, Sanne E', 'Akhtar, Hashaam', 'Siupka, Piotr', 'Pietschmann, Thomas', 'Thiel, Volker', 'Hartmann, Rune']",,,,
,PMC,Gene regulation by noncoding RNAs,http://dx.doi.org/10.3109/10409238.2013.844092,PMC4721600,,,"The past two decades have seen an explosion in research on noncoding RNAs and their physiological and pathological functions. Several classes of small (20–30 nucleotides) and long (>200 nucleotides) noncoding RNAs have been firmly established as key regulators of gene expression in myriad processes ranging from embryonic development to innate immunity. In this review, we focus on our current understanding of the molecular mechanisms underlying the biogenesis and function of small interfering RNAs (siRNAs), microRNAs (miRNAs), and Piwi-interacting RNAs (piRNAs). In addition, we briefly review the relevance of small and long noncoding RNAs to human physiology and pathology and their potential to be exploited as therapeutic agents.",,"['Patil, Veena S.', 'Zhou, Rui', 'Rana, Tariq M.']",,,,
,PMC,Viroporin activity of the JC polyomavirus is regulated by interactions with the adaptor protein complex 3,http://dx.doi.org/10.1073/pnas.1311457110,PMC3832026,,,"Viroporins, which are encoded by a wide range of animal viruses, oligomerize in host cell membranes and form hydrophilic pores that can disrupt a number of physiological properties of the cell. Little is known about the relationship between host cell proteins and viroporin activity. The human JC polyomavirus (JCV) is the causative agent of progressive multifocal leukoencephalopathy. The JCV-encoded agnoprotein, which is essential for viral replication, has been shown to act as a viroporin. Here we demonstrate that the JCV agnoprotein specifically interacts with adaptor protein complex 3 through its δ subunit. This interaction interrupts adaptor protein complex 3–mediated vesicular trafficking with suppression of the targeting of the protein to the lysosomal degradation pathway and instead permits the transport of agnoprotein to the cell surface with resulting membrane permeabilization. The findings demonstrate a previously undescribed paradigm in virus–host interactions allowing the host to regulate viroporin activity and suggest that the viroporins of other viruses may also be highly regulated by specific interactions with host cell proteins.",,"['Suzuki, Tadaki', 'Orba, Yasuko', 'Makino, Yoshinori', 'Okada, Yuki', 'Sunden, Yuji', 'Hasegawa, Hideki', 'Hall, William W.', 'Sawa, Hirofumi']",,,,
,PMC,Confounding roles for type I interferons during bacterial and viral pathogenesis,http://dx.doi.org/10.1093/intimm/dxt050,PMC3839063,,,"Although type I interferons (IFN-I) were initially defined as potent antiviral agents, they can also cause decreased host resistance to some bacterial and viral infections. The many antiviral functions of the IFN-I include direct suppression of viral replication and activation of the immune response against viruses. In addition to their antiviral effects, IFN-I are also protective against several extracellular bacterial infections, in part, by promoting the induction of TNF-α and nitric oxide. In contrast, there is a negative effect of IFN-I on host resistance during chronic infection with lymphocytic choriomeningitis virus (LCMV) and acute infections with intracellular bacteria. In the case of LCMV, chronic IFN-I signaling induces adaptive immune system suppression. Blockade of IFN-I signaling removes the suppression and allows CD4 T-cell- and IFN-γ-mediated resolution of the infection. During acute intracellular bacterial infection, IFN-I suppress innate immunity by at least two defined mechanisms. During Francisella infection, IFN-I prevent IL-17 upregulation on γδ T cells and neutrophil recruitment. Following Listeria infection, IFN-I promote the cell death of macrophages and lymphocytes, which leads to innate immune suppression. These divergent findings for the role of IFN-I on pathogen control emphasize the complexity of the interferons system and force more mechanistic evaluation of its role in pathogenesis. This review evaluates IFN-I during infection with an emphasis on work carried out IFN-I-receptor-deficient mice.",,"Carrero, Javier Antonio",,,,
,PMC,Sociotechnical Challenges and Progress in Using Social Media for Health,http://dx.doi.org/10.2196/jmir.2792,PMC3806390,24148206,CC BY,"Social media tools that connect patients, caregivers, and health providers offer great potential for helping people access health advice, receive and give social support, manage or cope with chronic conditions, and make day-to-day health decisions. These systems have seen widespread adoption, but often fail to support the goals as fully as designers and users would like. Through Ackerman’s lens of the “sociotechnical gap” and computer supported cooperative work (CSCW) as a science of the artificial, we review contemporary sociotechnical challenges and progress for using social media to support health. These challenges include a tension between privacy and sharing, policy information credibility, accessibility, and tailoring in social spaces. Those studying, building, deploying, and using social media systems to further health goals will benefit from approaching this work by borrowing from Ackerman’s framing of CSCW. In particular, this requires acknowledgment that technical systems will not fully meet our social goals, and then adopting design and educational approaches that are appropriate to fill this gap, building less-nuanced systems as partial solutions and tools for advancing our understanding, and by working with the CSCW research community to develop and pursue key lines of inquiry.",2013 Oct 22,"['Munson, Sean A', 'Cavusoglu, Hasan', 'Frisch, Larry', 'Fels, Sidney']",J Med Internet Res,,,
,PMC,Protein Engineering Strategies for the Development of Viral Vaccines and Immunotherapeutics,http://dx.doi.org/10.1016/j.febslet.2013.10.014,PMC3947166,,,"Vaccines that elicit a protective broadly neutralizing antibody (bNAb) response and monoclonal antibody therapies are critical for the treatment and prevention of viral infections. However, isolation of protective neutralizing antibodies has been challenging for some viruses, notably those with high antigenic diversity or those that do not elicit a bNAb response in the course of natural infection. Here, we discuss recent work that employs protein engineering strategies to design immunogens that elicit bNAbs or engineer novel bNAbs. We highlight the use of rational, computational, and combinatorial strategies and assess the potential of these approaches for the development of new vaccines and immunotherapeutics.",,"['Koellhoffer, Jayne F.', 'Higgins, Chelsea D.', 'Lai, Jonathan R.']",,,,
,PMC,Profile of Dennis Lo,http://dx.doi.org/10.1073/pnas.1317868110,PMC3839783,,,,,"Viegas, Jennifer",,,,
,PMC,Lipids in innate anti-viral defense,http://dx.doi.org/10.1016/j.chom.2013.09.010,PMC3850052,,,"It is becoming apparent that infections by a major class of viruses, those with envelopes, can be inhibited during their entry at the step of fusion with cellular membranes. In this review, we discuss multiple innate immune mechanisms that have evolved to modify the lipid composition of cellular and viral membranes to inhibit virion fusion of enveloped viruses.",,"['Schoggins, John W.', 'Randall, Glenn']",,,,
,PMC,Epidemiology and Clinical Presentation of Parainfluenza Type 4 in Children: A 3-Year Comparative Study to Parainfluenza Types 1–3,http://dx.doi.org/10.1093/infdis/jit552,PMC3923541,,,"Background. Human parainfluenza viruses (HPIVs) are among the most common causes of respiratory tract infections in children. Little is known about the epidemiology and clinical presentation of HPIV type 4. Methods. A retrospective chart review and comparison of patients positive for HPIV types 1–4 by multiplex polymerase chain reaction between 2009 and 2012 at Children's Hospital Colorado was performed. Patients who had only direct fluorescent antibody testing performed or concurrent viral infections were excluded. Results. Of 11 533 samples, 752 (6.5%) were positive for HPIV. After exclusion criteria, 316 samples were included in the study. HPIV-4 had year-round prevalence with biennial peaks in odd-numbered years. HPIV-4 and HPIV-3 had similar clinical presentations. 50.8% and 51.5% of patients with HPIV-3–4 had hypoxia compared to 20.3% and 33.3% of patients with HPIV-1–2 (P < .01). HPIV-1 (23.6%) and HPIV-2 (24.2%) were more associated with stridor than HPIV-3 (6.6%) and HPIV-4 (0%) (P < .01). No patients with HPIV-4 had croup. Patients with HPIV-4 had similar lengths of stay and mortality as those with HPIV-1–3. Conclusions. This is the first large-scale analysis of HPIV-4 clinical and epidemiologic features. HPIV-4 was most similar to HPIV-3 in clinical presentation. HPIV-4 had year-round prevalence with peaks in the autumn of odd-numbered years. HPIV-4 is a common respiratory pathogen capable of causing significant morbidity in children.",,"['Frost, Holly M.', 'Robinson, Christine C.', 'Dominguez, Samuel R.']",,,,
,PMC,Croup in children,http://dx.doi.org/10.1503/cmaj.121645,PMC3796596,,,,,"['Bjornson, Candice L.', 'Johnson, David W.']",,,,
,PMC,Negative Regulation of Interferon-induced Transmembrane Protein 3 by SET7-mediated Lysine Monomethylation,http://dx.doi.org/10.1074/jbc.M113.511949,PMC3853261,,,"Although lysine methylation is classically known to regulate histone function, its role in modulating antiviral restriction factor activity remains uncharacterized. Interferon-induced transmembrane protein 3 (IFITM3) was found monomethylated on its lysine 88 residue (IFITM3-K88me1) to reduce its antiviral activity, mediated by the lysine methyltransferase SET7. Vesicular stomatitis virus and influenza A virus infection increased IFITM3-K88me1 levels by promoting the interaction between IFITM3 and SET7, suggesting that this pathway could be hijacked to support infection; conversely, IFN-α reduced IFITM3-K88me1 levels. These findings may have important implications in the design of therapeutics targeting protein methylation against infectious diseases.",,"['Shan, Zhao', 'Han, Qinglin', 'Nie, Jia', 'Cao, Xuezhi', 'Chen, Zuojia', 'Yin, Shuying', 'Gao, Yayi', 'Lin, Fang', 'Zhou, Xiaohui', 'Xu, Ke', 'Fan, Huimin', 'Qian, Zhikang', 'Sun, Bing', 'Zhong, Jin', 'Li, Bin', 'Tsun, Andy']",,,,
,PMC,Human bocavirus 1 infects commercially-available primary human airway epithelium cultures productively,http://dx.doi.org/10.1016/j.jviromet.2013.10.012,PMC3855471,,,"Human bocavirus 1 (HBoV1), a human parvovirus, belongs to the genus Bocavirus of the Parvoviridae family. It causes wheezing in young children with acute respiratory tract infections. HBoV1 has been shown to infect polarized human airway epithelium (HAE) made in house, and induces airway epithelial damage. In this study, two commercially-available HAE cultures, EpiAirway and MucilAir HAE, were examined for HBoV1 infection. Both HAE cultures support fully productive HBoV1 infection. Infected EpiAirway and MucilAir HAE cultures showed loss of cilia, disruption of the tight junction barrier, and a significant decrease in transepithelial electrical resistance. Notably, HBoV1 persistent infection was demonstrated by maintaining HBoV1-infected EpiAirway HAE for as long as 50 days. After 2 days post-infection, progeny virus was produced consistently daily at a level of over 2 × 10(8) viral genome copies per culture (0.6 cm(2)). This study is the first to use commercial sources of HAE cultures for HBoV1 infection. The availability of these cultures will enable a wide range of laboratories to study HBoV1 infection.",,"['Deng, Xuefeng', 'Li, Yi', 'Qiu, Jianming']",,,,
,PMC,Rescue of Recombinant Newcastle Disease Virus from cDNA,http://dx.doi.org/10.3791/50830,PMC3939320,,,"Newcastle disease virus (NDV), the prototype member of the Avulavirus genus of the family Paramyxoviridae(1), is a non-segmented, negative-sense, single-stranded, enveloped RNA virus (Figure 1) with potential applications as a vector for vaccination and treatment of human diseases. In-depth exploration of these applications has only become possible after the establishment of reverse genetics techniques to rescue recombinant viruses from plasmids encoding their complete genomes as cDNA(2-5). Viral cDNA can be conveniently modified in vitro by using standard cloning procedures to alter the genotype of the virus and/or to include new transcriptional units. Rescue of such genetically modified viruses provides a valuable tool to understand factors affecting multiple stages of infection, as well as allows for the development and improvement of vectors for the expression and delivery of antigens for vaccination and therapy. Here we describe a protocol for the rescue of recombinant NDVs.",,"['Ayllon, Juan', 'García-Sastre, Adolfo', 'Martínez-Sobrido, Luis']",,,,
,PMC,Assays for the Identification of Novel Antivirals against Bluetongue Virus,http://dx.doi.org/10.3791/50820,PMC3939319,,,"To identify potential antivirals against BTV, we have developed, optimized and validated three assays presented here. The CPE-based assay was the first assay developed to evaluate whether a compound showed any antiviral efficacy and have been used to screen large compound library. Meanwhile, cytotoxicity of antivirals could also be evaluated using the CPE-based assay. The dose-response assay was designed to determine the range of efficacy for the selected antiviral, i.e. 50% inhibitory concentration (IC(50)) or effective concentration (EC(50)), as well as its range of cytotoxicity (CC(50)). The ToA assay was employed for the initial MoA study to determine the underlying mechanism of the novel antivirals during BTV viral lifecycle or the possible effect on host cellular machinery. These assays are vital for the evaluation of antiviral efficacy in cell culture system, and have been used for our recent researches leading to the identification of a number of novel antivirals against BTV.",,"['Gu, Linlin', 'Schneller, Stewart W.', 'Li, Qianjun']",,,,
,PMC,"Design, synthesis and biological evaluation of phosphorodiamidate prodrugs of antiviral and anticancer nucleosides",http://dx.doi.org/10.1016/j.ejmech.2013.09.047,PMC4358806,,,"We herein report the application of the phosphorodiamidate phosphate prodrug approach to a series of thirteen nucleoside analogs with antiviral or anticancer activity. Twenty-five symmetrical phosphorodiamidates were synthesized, bearing esterified l-Alanine (and in one case d-alanine) in the prodrug moiety, each as single stereoisomer. The presence of an achiral phosphorus represents a potential advantage over the phosphoramidate ProTide approach, where diastereoisomeric mixtures are routinely obtained, and different biological profiles may be expected from the diastereoisomers. Optimization of the synthetic pathway allowed us to identify two general methods depending on the particular nucleoside analogs. All the compounds were biologically evaluated in antiviral and anticancer assays and several showed improvement of activity compared to their parent nucleosides, as in the case of ddA, d4T, abacavir and acyclovir against HIV-1 and/or HIV-2. The biological results were supported by metabolism studies with carboxypeptidase Y monitored by (31)P NMR to investigate their bioactivation. This work further validates the phosphorodiamidate approach as a monophosphate prodrug motif with broad application in the antiviral and anticancer fields.",,"['McGuigan, Christopher', 'Bourdin, Claire', 'Derudas, Marco', 'Hamon, Nadège', 'Hinsinger, Karen', 'Kandil, Sahar', 'Madela, Karolina', 'Meneghesso, Silvia', 'Pertusati, Fabrizio', 'Serpi, Michaela', 'Slusarczyk, Magdalena', 'Chamberlain, Stanley', 'Kolykhalov, Alexander', 'Vernachio, John', 'Vanpouille, Christophe', 'Introini, Andrea', 'Margolis, Leonid', 'Balzarini, Jan']",,,,
,PMC,Proteolytic activation of the SARS-coronavirus spike protein: Cutting enzymes at the cutting edge of antiviral research,http://dx.doi.org/10.1016/j.antiviral.2013.09.028,PMC3889862,,,"The severe acute respiratory syndrome (SARS) pandemic revealed that zoonotic transmission of animal coronaviruses (CoV) to humans poses a significant threat to public health and warrants surveillance and the development of countermeasures. The activity of host cell proteases, which cleave and activate the SARS-CoV spike (S) protein, is essential for viral infectivity and constitutes a target for intervention. However, the identities of the proteases involved have been unclear. Pioneer studies identified cathepsins and type II transmembrane serine proteases as cellular activators of SARS-CoV and demonstrated that several emerging viruses might exploit these enzymes to promote their spread. Here, we will review the proteolytic systems hijacked by SARS-CoV for S protein activation, we will discuss their contribution to viral spread in the host and we will outline antiviral strategies targeting these enzymes. This paper forms part of a series of invited articles in Antiviral Research on “From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.”",,"['Simmons, Graham', 'Zmora, Pawel', 'Gierer, Stefanie', 'Heurich, Adeline', 'Pöhlmann, Stefan']",,,,
,PMC,Fatal measles pneumonitis during Hodgkin's lymphoma,http://dx.doi.org/10.1136/bcr-2013-200252,PMC3822100,,,"The treatment of measles pneumonitis in immunocompromised adults is not established. We describe a patient with Hodgkin's lymphoma who developed acute pneumonia during a measles infection. On day 13, intravenous ribavirin and immunoglobulins were administrated. On day 18, the patient developed acute respiratory failure. An examination of transbronchial pulmonary biopsies showed Warthin-Finkeldey giant cells that are pathognomonic of measles pneumonitis. The patient died despite aggressive supportive care. Our case and a review of literature show that measles pneumonitis is routinely fatal in patients with cancer. We suggest that antiviral drugs should be considered as soon as the diagnosis has been established.",,"['Wyplosz, Benjamin', 'Lafarge, Marion', 'Escaut, Lélia', 'Stern, Jean-Baptiste']",,,,
,PMC,Role of Human Bocavirus in Upper Respiratory Tract Infections and Acute Otitis Media,http://dx.doi.org/10.1093/jpids/pit061,PMC4865000,,,"BACKGROUND: Human bocavirus (HBoV) is a newly described parvovirus. HBoV1 has been associated with respiratory infections, including acute otitis media (AOM), but the knowledge on the significance of HBoV1 in upper respiratory tract infections (URI) and AOM in relation to other respiratory viruses is limited. The objective of this study was to compare the rate of detection of HBoV1 to that of other respiratory viruses in specimens from children with URI, with and without AOM complication. METHODS: Nasopharyngeal secretions (NPS) were collected during URI from healthy children (6–35 months) followed prospectively for 1 year; specimens have been previously analyzed for broad spectrum of respiratory viruses. Archived NPS were analyzed for HBoV1 using a high-throughput, quantitative polymerase chain reaction method. RESULTS: Seven hundred and seven NPS samples collected during URI episodes from 201 children were studied for HBoV1. A total of 94 (47%) children tested positive for HBoV1 DNA during 172 (24%) URI episodes; HBoV1 was present as the only virus in 44 (6%) URI episodes. Overall, 37% of URI episodes were complicated by AOM. Of URI associated with single virus (n = 303), the rate of AOM complicating URI associated with HBoV1 only was 52% (23 of 44); this was a higher AOM rate, compared to that of other respiratory viruses. CONCLUSIONS: Among URI associated with single respiratory virus, HBoV1-URI was commonly associated with AOM complication. The important role of HBoV1 on AOM pathogenesis needs to be studied further.",,"['Nokso-Koivisto, Johanna', 'Pyles, Richard B.', 'Miller, Aaron L.', 'Jennings, Kristofer', 'Loeffelholz, Michael', 'Chonmaitree, Tasnee']",,,,
,PMC,The price of anarchy in mobility-driven contagion dynamics,http://dx.doi.org/10.1098/rsif.2013.0495,PMC3758010,,,"Public policy and individual incentives determine the patterns of human mobility through transportation networks. In the event of a health emergency, the pursuit of maximum social or individual utility may lead to conflicting objectives in the routing strategies of network users. Individuals tend to avoid exposure so as to minimize the risk of contagion, whereas policymakers aim at coordinated behaviour that maximizes the social welfare. Here, we study agent-driven contagion dynamics through transportation networks, coupled to the adoption of either selfish- or policy-driven rerouting strategies. In analogy with the concept of price of anarchy in transportation networks subject to congestion, we show that maximizing individual utility leads to a loss of welfare for the social group, measured here by the total population infected after an epidemic outbreak.",,"['Nicolaides, Christos', 'Cueto-Felgueroso, Luis', 'Juanes, Ruben']",,,,
,PMC,Safety and Infectivity of Two Doses of Live -Attenuated Recombinant Cold-Passaged Human Parainfluenza Type 3 Virus Vaccine rHPIV3cp45 in HPIV3-Seronegative Young Children,http://dx.doi.org/10.1016/j.vaccine.2013.09.046,PMC3889708,,,"BACKGROUND: Human parainfluenza virus type 3 (HPIV3) is a common cause of upper and lower respiratory tract illness in infants and young children. Live-attenuated cold-adapted HPIV3 vaccines have been evaluated in infants but a suitable interval for administration of a second dose of vaccine has not been defined. METHODS: HPIV3-seronegative children between the ages of 6 and 36 months were randomized 2:1 in a blinded study to receive two doses of 10(5) TCID(50) (50% tissue culture infectious dose) of live-attenuated, recombinant cold-passaged human PIV3 vaccine (rHPIV3cp45) or placebo 6 months apart. Serum antibody levels were assessed prior to and approximately 4-6 weeks after each dose. Vaccine virus infectivity, defined as detection of vaccine-HPIV3 in nasal wash and/or a ≥ 4-fold rise in serum antibody titer, and reactogenicity were assessed on days 3, 7, and 14 following immunization. RESULTS: Forty HPIV3-seronegative children (median age 13 months; range 6-35 months) were enrolled; 27 (68%) received vaccine and 13 (32%) received placebo. Infectivity was detected in 25 (96%) of 26 evaluable vaccinees following dose 1 and 9 of 26 subject (35%) following dose 2. Among those who shed virus, the median duration of viral shedding was 12 days (range, 6-15 days) after dose 1 and 6 days (range 3-8 days) after dose 2, with a mean peak log(10) viral titer of 3.4 PFU/mL (SD: 1.0) after dose 1 compared to1.5 PFU/mL (SD: 0.92) after dose 2. Overall, reactogenicity was mild, with no difference in rates of fever and upper respiratory infection symptoms between vaccine and placebo groups. CONCLUSION: rHPIV3cp45 was immunogenic and well-tolerated in seronegative young children. A second dose administered 6 months after the initial dose was restricted in those previously infected with vaccine virus; however, the second dose boosted antibody responses and induced antibody responses in two previously uninfected children.",,"['Englund, Janet A.', 'Karron, Ruth A.', 'Cunningham, Coleen K', 'LaRussa, Philip', 'Melvin, Ann', 'Yogev, Ram', 'Handelsman, Ed', 'Siberry, George K', 'Thumar, Bhavanji', 'Schappell, Elizabeth', 'Bull, Catherine V.', 'Chu, Helen Y.', 'Schaap-Nutt, Anne', 'Buchholz, Ursula', 'Collins, Peter L.', 'Schmidt, Alexander C.', None]",,,,
,PMC,Prospective Evaluation for Respiratory Pathogens in Children With Sickle Cell Disease and Acute Respiratory Illness,http://dx.doi.org/10.1002/pbc.24798,PMC4632201,,,"BACKGROUND: Human rhinovirus (HRV), human coronavirus (hCoV), human bocavirus (hBoV), and human metapneumovirus (hMPV) infections in children with sickle cell disease have not been well studied. PROCEDURE: Nasopharyngeal wash specimens were prospectively collected from 60 children with sickle cell disease and acute respiratory illness, over a 1-year period. Samples were tested with multiplexed-PCR, using an automated system for nine respiratory viruses, Chlamydophila pneumoniae, Mycoplasma pneumoniae, and Bordetella pertussis. Clinical characteristics and distribution of respiratory viruses in patients with and without acute chest syndrome (ACS) were evaluated. RESULTS: A respiratory virus was detected in 47 (78%) patients. Nine (15%) patients had ACS; a respiratory virus was detected in all of them. The demographic characteristics of patients with and without ACS were similar. HRV was the most common virus, detected in 29 of 47 (62%) patients. Logistic regression showed no association between ACS and detection of HRV, hCoV, hBoV, hMPV, and other respiratory pathogens. Co-infection with at least one additional respiratory virus was seen in 14 (30%) infected patients, and was not significantly higher in patients with ACS (P=0.10). Co-infections with more than two respiratory viruses were seen in seven patients, all in patients without ACS. Bacterial pathogens were not detected. CONCLUSION: HRV was the most common virus detected in children with sickle cell disease and acute respiratory illness, and was not associated with increased morbidity. Larger prospective studies with asymptomatic controls are needed to study the association of these emerging respiratory viruses with ACS in children with sickle cell disease.",,"['Srinivasan, Ashok', 'Wang, Winfred C.', 'Gaur, Aditya', 'Smith, Teresa', 'Gu, Zhengming', 'Kang, Guolian', 'Leung, Wing', 'Hayden, Randall T.']",,,,
,PMC,Social and biological contagions,http://dx.doi.org/10.1126/science.1244492,PMC4229037,,,The coupling of social and biological contagion in human populations can have positive or negative outcomes.,,"['Bauch, Chris T.', 'Galvani, Alison P.']",,,,
,PMC,The antiviral activities of ISG15,http://dx.doi.org/10.1016/j.jmb.2013.09.041,PMC4090058,,,"Post-translational protein modification is an important strategy for the regulation of the cell proteome independent of the need for new gene expression. Ubiquitin and ubiquitin-like modifiers mediate the regulation of protein levels, signaling pathways, vesicular trafficking, and many other cellular processes through their covalent conjugation to proteins. Interferon stimulated gene 15 (ISG15) is a type I interferon induced ubiquitin-like modifier. In addition to conjugating to potentially hundreds of target proteins, ISG15 can be found in an unconjugated form both inside of the cell and released from interferon stimulated cells into the extracellular environment. Due to its robust expression after type I interferon stimulation and the broad panel of proteins that it targets, ISG15 has drawn much attention as a potential regulator of the immune response and has been shown to mediate protection in a number of different viral infection models. Here we will review the current state of the field of ISG15, the viruses against which ISG15 mediates protection, and the mechanisms by which ISG15 exerts antiviral activity.",,"['Morales, David J.', 'Lenschow, Deborah J.']",,,,
,PMC,Antiviral Mechanisms of Human Defensins,http://dx.doi.org/10.1016/j.jmb.2013.09.038,PMC3842434,,,"Defensins are an effector component of the innate immune system with broad antimicrobial activity. Humans express two types of defensins, α- and β-defensins, which have antiviral activity against both enveloped and non-enveloped viruses. The diversity of defensin-sensitive viral species reflects a multitude of antiviral mechanisms. These include direct defensin targeting of viral envelopes, glycoproteins, and capsids in addition to inhibition of viral fusion and post-entry neutralization. Binding and modulation of host cell surface receptors and disruption of intracellular signaling by defensins can also inhibit viral replication. In addition, defensins can function as chemokines to augment and alter adaptive immune responses, revealing an indirect antiviral mechanism. Nonetheless, many questions regarding the antiviral activities of defensins remain. Although significant mechanistic data is known for α-defensins, molecular details for β-defensin inhibition are mostly lacking. Importantly, the role of defensin antiviral activity in vivo has not been addressed due to the lack of a complete defensin knockout model. Overall, the antiviral activity of defensins is well established as are the variety of mechanisms by which defensins achieve this inhibition; however, additional research is needed to fully understand the role of defensins in viral pathogenesis.",,"['Wilson, Sarah S.', 'Wiens, Mayim E.', 'Smith, Jason G.']",,,,
,PMC,Of diabetic mice and ACE2: a new biomarker of renal disease?,http://dx.doi.org/10.1152/ajprenal.00403.2013,PMC3798742,,,,,"Chappell, Mark C.",,,,
,PMC,"Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases. Comprehensive Review of the Recent Literature 2010–2012",http://dx.doi.org/10.1513/AnnalsATS.201304-090AW,PMC3960908,,,"A conference, “Stem Cells and Cell Therapies in Lung Biology and Lung Diseases,” was held July 25 to 28, 2011 at the University of Vermont to review the current understanding of the role of stem and progenitor cells in lung repair after injury and to review the current status of cell therapy and ex vivo bioengineering approaches for lung diseases. These are rapidly expanding areas of study that provide further insight into and challenge traditional views of mechanisms of lung repair after injury and pathogenesis of several lung diseases. The goals of the conference were to summarize the current state of the field, to discuss and debate current controversies, and to identify future research directions and opportunities for basic and translational research in cell-based therapies for lung diseases. The goal of this article, which accompanies the formal conference report, is to provide a comprehensive review of the published literature in lung regenerative medicine from the last conference report through December 2012.",,"Weiss, Daniel J.",,,,
,PMC,"A Novel, Broad-Spectrum Inhibitor of Enterovirus Replication That Targets Host Cell Factor Phosphatidylinositol 4-Kinase IIIβ",http://dx.doi.org/10.1128/AAC.01175-13,PMC3811463,,,"Despite their high clinical and socioeconomic impacts, there is currently no approved antiviral therapy for the prophylaxis or treatment of enterovirus infections. Here we report on a novel inhibitor of enterovirus replication, compound 1, 2-fluoro-4-(2-methyl-8-(3-(methylsulfonyl)benzylamino)imidazo[1,2-a]pyrazin-3-yl)phenol. This compound exhibited a broad spectrum of antiviral activity, as it inhibited all tested species of enteroviruses and rhinoviruses, with 50% effective concentrations ranging between 4 and 71 nM. After a lengthy resistance selection process, coxsackievirus mutants resistant to compound 1 were isolated that carried substitutions in their 3A protein. Remarkably, the same substitutions were recently shown to provide resistance to inhibitors of phosphatidylinositol 4-kinase IIIβ (PI4KIIIβ), a lipid kinase that is essential for enterovirus replication, suggesting that compound 1 may also target this host factor. Accordingly, compound 1 directly inhibited PI4KIIIβ in an in vitro kinase activity assay. Furthermore, the compound strongly reduced the PI 4-phosphate levels of the Golgi complex in cells. Rescue of coxsackievirus replication in the presence of compound 1 by a mutant PI4KIIIβ carrying a substitution in its ATP-binding pocket revealed that the compound directly binds the kinase at this site. Finally, we determined that an analogue of compound 1, 3-(3-fluoro-4-methoxyphenyl)-2-methyl-N-(pyridin-4-ylmethyl)imidazo[1,2-a]pyrazin-8-amine, is well tolerated in mice and has a dose-dependent protective activity in a coxsackievirus serotype B4-induced pancreatitis model.",,"['van der Schaar, Hilde M.', 'Leyssen, Pieter', 'Thibaut, Hendrik J.', 'de Palma, Armando', 'van der Linden, Lonneke', 'Lanke, Kjerstin H. W.', 'Lacroix, Céline', 'Verbeken, Erik', 'Conrath, Katja', 'MacLeod, Angus M.', 'Mitchell, Dale R.', 'Palmer, Nicholas J.', 'van de Poël, Hervé', 'Andrews, Martin', 'Neyts, Johan', 'van Kuppeveld, Frank J. M.']",,,,
,PMC,Angiotensin Peptides and Nitric Oxide in Cardiovascular Disease,http://dx.doi.org/10.1089/ars.2012.4614,PMC3771546,,,"Significance: The renin-angiotensin system (RAS) plays an important role in the normal control of cardiovascular and renal function in the healthy state and is a contributing factor in the development and progression of various types of cardiovascular diseases (CVD), including hypertension, diabetes, and heart failure. Recent Advances: Evidence suggests that a balance between activation of the ACE/Ang II/AT1 receptor axis and the ACE2/Ang-(1–7)/Mas receptor axis is important for the function of the heart, kidney, and autonomic nervous system control of the circulation in the normal healthy state. An imbalance in these opposing pathways toward the ACE/Ang II/AT1 receptor axis is associated with CVD. The key component of this imbalance with respect to neural control of the circulation is the negative interaction between oxidative and NO(•) mechanisms, which leads to enhanced sympathetic tone and activation in disease conditions such as hypertension and heart failure. Critical Issues: The key mechanisms that disrupt normal regulation of Ang II and Ang-(1–7) signaling and promote pathogenesis of CVD at all organ levels remain poorly understood. The reciprocal relation between ACE and ACE2 expression and function suggests they are controlled interdependently at pre- and post-translational levels. Insights from neural studies suggest that an interaction between oxidative and nitrosative pathways may be key. Future Directions: The role of redox mechanisms in the control of expression and activity of RAS enzymes and Ang receptors may provide important insight into the function of local tissue RAS in health and disease. Antioxid. Redox Signal. 19, 1121–1132.",,"['Patel, Kaushik P.', 'Schultz, Harold D.']",,,,
,PMC,Stage of the Estrous Cycle Does Not Influence Myocardial Ischemia–Reperfusion Injury in Rats (Rattus norvegicus),,PMC3796752,,,"Even though cardiovascular disease is the leading cause of death for men and women, the vast majority of animal studies use male animals. Because female reproductive hormones have been associated with cardioprotective states, many investigators avoid using female animals because these hormones are cyclical and may introduce experimental variability. In addition, no studies have investigated the specific effects of the estrous cycle on cardiac ischemic injury. This study was conducted to determine whether the estrous cycle stage influences the susceptibility to ischemic injury in rat hearts. Estrous cycle stage was determined by using vaginal smear cytology, after which hearts underwent either in vivo (surgical) or ex vivo (isolated) ischemia–reperfusion injury. For in vivo studies, the left anterior coronary artery was ligated for 25 min of ischemia and subsequently released for 120 min of reperfusion. Infarct sizes were 42% ± 6%; 49% ± 4%; 40% ± 9%; 47% ± 9% of the zone-at-risk for rats in proestrus, estrus, metestrus, and diestrus, respectively. For ex vivo studies, isolated, perfused hearts underwent global ischemia and reperfusion for 25 and 120 min, respectively. Similar to our in vivo studies, the ex vivo rat model showed no significant differences in susceptibility to infarction or extent of cardiac arrhythmia according to estrous stage. To our knowledge, these studies provide the first direct evidence that the stage of estrous cycle does not significantly alter cardiac ischemia–reperfusion injury in rats.",,"['Frasier, Chad R', 'Brown, David A', 'Sloan, Ruben C', 'Hayes, Brian', 'Stewart, Luke M', 'Patel, Hetal D', 'Lust, Robert M', 'Rosenbaum, Matthew D']",,,,
,PMC,A Systems Framework for Vaccine Design,,PMC3983719,,,"Numerous challenges have been identified in vaccine development, including variable efficacy as a function of population demographics and a lack of characterization and mechanistic understanding of immune correlates of protection able to guide delivery and dosing. There is tremendous opportunity in recent technological and computational advances to elucidate systems level understanding of pathogen-host interactions and correlates of immunity. A systems biology approach to vaccinology provides a new paradigm for rational vaccine design in a “precision medicine” context.",,"['Mooney, Michael', 'McWeeney, Shannon', 'Canderan, Glenda', 'Sékaly, Rafick-Pierre']",,,,
,PMC,Viroporins Customize Host Cells for Efficient Viral Propagation,http://dx.doi.org/10.1089/dna.2013.2159,PMC3785214,,,"Viruses are intracellular parasites that must access the host cell machinery to propagate. Viruses hijack the host cell machinery to help with entry, replication, packaging, and release of progeny to infect new cells. To carry out these diverse functions, viruses often transform the cellular environment using viroporins, a growing class of viral-encoded membrane proteins that promote viral proliferation. Viroporins modify the integrity of host membranes, thereby stimulating the maturation of viral infection, and are critical for virus production and dissemination. Significant advances in molecular and cell biological approaches have helped to uncover some of the roles that viroporins serve in the various stages of the viral life cycle. In this study, the ability of viroporins to modify the cellular environment will be discussed, with particular emphasis on their role in the stepwise progression of the viral life cycle.",,"['Giorda, Kristina M.', 'Hebert, Daniel N.']",,,,
,PMC,SIN-dependent phosphoinhibition of formin multimerization controls fission yeast cytokinesis,http://dx.doi.org/10.1101/gad.224154.113,PMC3850099,,,"Many eukaryotes accomplish cell division by building and constricting a medial actomyosin-based cytokinetic ring (CR). In Schizosaccharomyces pombe, a Hippo-related signaling pathway termed the septation initiation network (SIN) controls CR formation, maintenance, and constriction. However, how the SIN regulates integral CR components was unknown. Here, we identify the essential cytokinetic formin Cdc12 as a key CR substrate of SIN kinase Sid2. Eliminating Sid2-mediated Cdc12 phosphorylation leads to persistent Cdc12 clustering, which prevents CR assembly in the absence of anillin-like Mid1 and causes CRs to collapse when cytokinesis is delayed. Molecularly, Sid2 phosphorylation of Cdc12 abrogates multimerization of a previously unrecognized Cdc12 domain that confers F-actin bundling activity. Taken together, our findings identify a SIN-triggered oligomeric switch that modulates cytokinetic formin function, revealing a novel mechanism of actin cytoskeleton regulation during cell division.",,"['Bohnert, K. Adam', 'Grzegorzewska, Agnieszka P.', 'Willet, Alaina H.', 'Vander Kooi, Craig W.', 'Kovar, David R.', 'Gould, Kathleen L.']",,,,
,PMC,Pathogen safety of long-term treatments for bleeding disorders: still relevant to current practice,http://dx.doi.org/10.3324/haematol.2013.084145,PMC3789452,,,,,"['Di Minno, Giovanni', 'Canaro, Mariana', 'Ironside, James W.', 'Navarro, David', 'Perno, Carlo Federico', 'Tiede, Andreas', 'Gürtler, Lutz']",,,,
,PMC,Gene Therapy Briefs,http://dx.doi.org/10.1089/hum.2013.2510,PMC3787461,,,,,"Philippidis, Alex",,,,
,PMC,Reverse Transcription-PCR–Electrospray Ionization Mass Spectrometry for Rapid Detection of Biothreat and Common Respiratory Pathogens,http://dx.doi.org/10.1128/JCM.01443-13,PMC3811651,,,"Electrospray ionization mass spectrometry (ESI-MS) analysis of reverse transcription (RT)-PCR amplicons from human respiratory samples allows for broad pathogen identification approximately 8 h after collection. We investigated the performance characteristics of a high-throughput RT-PCR-coupled ESI-MS assay for distinguishing biothreat (BT) agents from common bacterial, fungal, and viral respiratory pathogens in bronchoalveolar lavage (BAL) fluid specimens from subjects with suspected respiratory infections. In a retrospective case series, 202 BAL fluid specimens were collected at the Johns Hopkins Hospital between August 2010 and February 2011 from patients with suspected acute respiratory infections. Samples were processed using standard bacterial, viral, and fungal testing in the clinical microbiology laboratory as part of routine care and then were blindly spiked with either water or nucleic acids from BT organisms (Bacillus anthracis, Yersinia pestis, Francisella tularensis, Brucella spp., Burkholderia spp., and Rickettsia prowazekii) and tested by RT-PCR–ESI-MS. The sensitivities and specificities of RT-PCR–ESI-MS versus standard clinical methods were as follows: for mock BT DNA, 98.5% sensitivity (95% confidence interval [CI], 94.2 to 99.7%) and 100% specificity (95% CI, 93.1 to 100.0%); for bacterial pathogens, 81.8% sensitivity (95% CI, 74.3 to 87.6%) and 73.6% specificity (95% CI, 64.2 to 81.4%); for viral pathogens, 93.3% sensitivity (95% CI, 66.0 to 99.7%) and 97.3% specificity (95% CI, 89.7 to 99.5%); for fungal pathogens, 42.6% sensitivity (95% CI, 29.5 to 56.7%) and 97.8% specificity (95% CI, 91.8 to 99.6%). Our data suggest that RT-PCR–ESI-MS is a useful adjunct to standard culture protocols for rapid detection of both BT and common respiratory pathogens; further study is required for assay validation, especially for fungal detection, and potential implementation.",,"['Jeng, Kevin', 'Hardick, Justin', 'Rothman, Richard', 'Yang, Samuel', 'Won, Helen', 'Peterson, Stephen', 'Hsieh, Yu-Hsiang', 'Masek, Billie Jo', 'Carroll, Karen C.', 'Gaydos, Charlotte A.']",,,,
,PMC,Possible Involvement of Human Bocavirus 1 in the Death of a Middle-Aged Immunosuppressed Patient,http://dx.doi.org/10.1128/JCM.01157-13,PMC3811645,,,"An immunosuppressed 61-year-old man went to the hospital with fever, nonproductive cough, and increasing shortness of breath. The subject died 8 days later of respiratory complications. PCR of respiratory samples as well as a blood sample revealed exceptionally high DNA levels of the emerging pathogen, human bocavirus 1 (HBoV1), a recently found pathogen associated with respiratory symptoms in young children. We describe the clinical progression of the case and discuss the potential role of HBoV1 in the outcome.",,"['Sadeghi, Mohammadreza', 'Kantola, Kalle', 'Finnegan, Damian P. J.', 'McCaughey, Conall', 'Hedman, Lea', 'Söderlund-Venermo, Maria', 'Hedman, Klaus']",,,,
,PMC,Crystal Structure of the Receptor-Binding Domain from Newly Emerged Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.01756-13,PMC3807420,,,"The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 77 people, with a fatality rate of more than 50%. Alarmingly, the virus demonstrates the capability of human-to-human transmission, raising the possibility of global spread and endangering world health and economy. Here we have identified the receptor-binding domain (RBD) from the MERS-CoV spike protein and determined its crystal structure. This study also presents a structural comparison of MERS-CoV RBD with other coronavirus RBDs, successfully positioning MERS-CoV on the landscape of coronavirus evolution and providing insights into receptor binding by MERS-CoV. Furthermore, we found that MERS-CoV RBD functions as an effective entry inhibitor of MERS-CoV. The identified MERS-CoV RBD may also serve as a potential candidate for MERS-CoV subunit vaccines. Overall, this study enhances our understanding of the evolution of coronavirus RBDs, provides insights into receptor recognition by MERS-CoV, and may help control the transmission of MERS-CoV in humans.",,"['Chen, Yaoqing', 'Rajashankar, Kanagalaghatta R.', 'Yang, Yang', 'Agnihothram, Sudhakar S.', 'Liu, Chang', 'Lin, Yi-Lun', 'Baric, Ralph S.', 'Li, Fang']",,,,
,PMC,"Expanded Cocirculation of Stable Subtypes, Emerging Lineages, and New Sporadic Reassortants of Porcine Influenza Viruses in Swine Populations in Northwest Germany",http://dx.doi.org/10.1128/JVI.00381-13,PMC3807404,,,"The emergence of the human 2009 pandemic H1N1 (H1N1pdm) virus from swine populations refocused public and scientific attention on swine as an important source of influenza A viruses bearing zoonotic potential. Widespread and year-round circulation of at least four stable lineages of porcine influenza viruses between 2009 and 2012 in a region of Germany with a high-density swine population is documented here. European avian influenza virus-derived H1N1 (H1N1av) viruses dominated the epidemiology, followed by human-derived subtypes H1N2 and H3N2. H1N1pdm viruses and, in particular, recently emerging reassortants between H1N1pdm and porcine HxN2 viruses (H1pdmN2) were detected in about 8% of cases. Further reassortants between these main lineages were diagnosed sporadically. Ongoing diversification both at the phylogenetic and at the antigenic level was evident for the H1N1av lineage and for some of its reassortants. The H1avN2 reassortant R1931/11 displayed conspicuously distinct genetic and antigenic features and was easily transmitted from pig to pig in an experimental infection. Continuing diverging evolution was also observed in the H1pdmN2 lineage. These viruses carry seven genome segments of the H1N1pdm virus, including a hemagglutinin gene that encodes a markedly antigenically altered protein. The zoonotic potential of this lineage remains to be determined. The results highlight the relevance of surveillance and control of porcine influenza virus infections. This is important for the health status of swine herds. In addition, a more exhaustive tracing of the formation, transmission, and spread of new reassortant influenza A viruses with unknown zoonotic potential is urgently required.",,"['Harder, Timm C.', 'grosse Beilage, Elisabeth', 'Lange, Elke', 'Meiners, Carolin', 'Döhring, Stefanie', 'Pesch, Stefan', 'Noé, Thomas', 'Grund, Christian', 'Beer, Martin', 'Starick, Elke']",,,,
,PMC,Morphological and Biochemical Characterization of the Membranous Hepatitis C Virus Replication Compartment,http://dx.doi.org/10.1128/JVI.01370-13,PMC3807400,,,"Like all other positive-strand RNA viruses, hepatitis C virus (HCV) induces rearrangements of intracellular membranes that are thought to serve as a scaffold for the assembly of the viral replicase machinery. The most prominent membranous structures present in HCV-infected cells are double-membrane vesicles (DMVs). However, their composition and role in the HCV replication cycle are poorly understood. To gain further insights into the biochemcial properties of HCV-induced membrane alterations, we generated a functional replicon containing a hemagglutinin (HA) affinity tag in nonstructural protein 4B (NS4B), the supposed scaffold protein of the viral replication complex. By using HA-specific affinity purification we isolated NS4B-containing membranes from stable replicon cells. Complementing biochemical and electron microscopy analyses of purified membranes revealed predominantly DMVs, which contained viral proteins NS3 and NS5A as well as enzymatically active viral replicase capable of de novo synthesis of HCV RNA. In addition to viral factors, co-opted cellular proteins, such as vesicle-associated membrane protein-associated protein A (VAP-A) and VAP-B, that are crucial for viral RNA replication, as well as cholesterol, a major structural lipid of detergent-resistant membranes, are highly enriched in DMVs. Here we describe the first isolation and biochemical characterization of HCV-induced DMVs. The results obtained underline their central role in the HCV replication cycle and suggest that DMVs are sites of viral RNA replication. The experimental approach described here is a powerful tool to more precisely define the molecular composition of membranous replication factories induced by other positive-strand RNA viruses, such as picorna-, arteri- and coronaviruses.",,"['Paul, David', 'Hoppe, Simone', 'Saher, Gesine', 'Krijnse-Locker, Jacomine', 'Bartenschlager, Ralf']",,,,
,PMC,Emergence of a C-Terminal Seven-Amino-Acid Elongation of NS1 in Around 1950 Conferred a Minor Growth Advantage to Former Seasonal Influenza A Viruses,http://dx.doi.org/10.1128/JVI.01271-13,PMC3807286,,,"Influenza A viruses circulating in humans from ∼1950 to ∼1987 featured a nonstructural (NS1) protein with a C-terminal extension of seven amino acids. The biological significance of this NS1 elongation remained elusive. We observed that replication kinetics of the wild-type virus A/Hong Kong/01/68 (H3N2) and a mutant encoding a truncated NS1 were indistinguishable in most experimental systems. However, wild-type virus outcompeted the mutant during mixed infections, suggesting that the NS1 extension conferred minor growth advantages.",,"['Lohrmann, Florens', 'Dijkman, Ronald', 'Stertz, Silke', 'Thiel, Volker', 'Haller, Otto', 'Staeheli, Peter', 'Kochs, Georg']",,,,
,PMC,Soluble Interleukin-6 Receptor-Mediated Innate Immune Response to DNA and RNA Viruses,http://dx.doi.org/10.1128/JVI.01248-13,PMC3807281,,,"The interleukin-6 (IL-6) receptor, which exists as membrane-bound and soluble forms, plays critical roles in the immune response. The soluble IL-6 receptor (sIL6R) has been identified as a potential therapeutic target for preventing coronary heart disease. However, little is known about the role of this receptor during viral infection. In this study, we show that sIL6R, but not IL-6, is induced by viral infection via the cyclooxygenase-2 pathway. Interestingly, sIL6R, but not IL-6, exhibited extensive antiviral activity against DNA and RNA viruses, including hepatitis B virus, influenza virus, human enterovirus 71, and vesicular stomatitis virus. No synergistic effects on antiviral action were observed by combining sIL6R and IL-6. Furthermore, sIL6R mediated antiviral action via the p28 pathway and induced alpha interferon (IFN-α) by promoting the nuclear translocation of IFN regulatory factor 3 (IRF3) and NF-κB, which led to the activation of downstream IFN effectors, including 2′,5′-oligoadenylate synthetase (OAS), double-stranded RNA-dependent protein kinase (PKR), and myxovirus resistance protein (Mx). Thus, our results demonstrate that sIL6R, but not IL-6, plays an important role in the host antiviral response.",,"['Wang, Qing', 'Chen, Xueyuan', 'Feng, Jian', 'Cao, Yanhua', 'Song, Yu', 'Wang, Hui', 'Zhu, Chengliang', 'Liu, Shi', 'Zhu, Ying']",,,,
,PMC,MATHEMATICAL MODELS OF CONTACT PATTERNS BETWEEN AGE GROUPS FOR PREDICTING THE SPREAD OF INFECTIOUS DISEASES,,PMC4002176,,,"The spread of an infectious disease is sensitive to the contact patterns in the population and to precautions people take to reduce the transmission of the disease. We investigate the impact that different mixing assumptions have on the spread an infectious disease in an age-structured ordinary differential equation model. We consider the impact of heterogeneity in susceptibility and infectivity within the population on the disease transmission. We apply the analysis to the spread of a smallpox-like disease, derive the formula for the reproduction number, [Formula: see text] , and based on this threshold parameter, show the level of human behavioral change required to control the epidemic. We analyze how different mixing patterns can affect the disease prevalence, the cumulative number of new infections, and the final epidemic size. Our analysis indicates that the combination of residual immunity and behavioral changes during a smallpox-like disease outbreak can play a key role in halting infectious disease spread; and that realistic mixing patterns must be included in the epidemic model for the predictions to accurately reflect reality.",,"['Del Valle, Sara Y.', 'Hyman, James M.', 'Chitnis, Nakul']",,,,
,PMC,RNA viruses: a case study of the biology of emerging infectious diseases,http://dx.doi.org/10.1128/microbiolspec.OH-0001-2012,PMC6157708,,,"There are 180 currently recognised species of RNA virus that can infect humans and, on average, 2 new species are added every year. RNA viruses are routinely exchanged between humans and other hosts (particularly other mammals and sometimes birds) over both epidemiological and evolutionary time: 89% of human-infective species are considered zoonotic and many of the remainder have zoonotic origins. Some viruses that have crossed the species barrier into humans have persisted, and become human-adapted viruses, as exemplified by the emergence of HIV-1. Most, however, have remained as zoonoses, and a substantial number have apparently disappeared again. We still know relatively little about what determines whether a virus is able to infect, transmit from and cause disease in humans, but there is evidence that factors such as host range, cell receptor usage, tissue tropisms and transmission route all play a role. Although systematic surveillance for potential new human viruses in non-human hosts would be enormously challenging, we can reasonably aspire much better knowledge of the diversity of mammalian and avian RNA viruses than exists at present.",,"['Woolhouse, Mark E.J.', 'Adair, Kyle', 'Brierley, Liam']",,,,
,PMC,Screening and Antiviral Analysis of Phages That Display Peptides with an Affinity to Subunit C of Porcine Aminopeptidase,http://dx.doi.org/10.1089/mab.2013.0038,PMC3798234,,,"The purified C subunit of the recombinant porcine aminopeptidase N (rpAPN-C) protein was used as an immobilized target to screen potential ligands against rpAPN-C from a 12-mer phage display random peptide library. After five rounds of biopanning, five phage clones showed specific binding affinities to rpAPN-C. In 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assays, the phage clone PM1, which contained the HDAISWTHYHPW peptide sequence, had a protective effect against TGEV infection in swine testis cells. Therefore, the HDAISWTHYHPW peptide sequence has a potential use as a small molecular therapeutic agent against TGEV infection.",,"['Guo, Donghua', 'Zhu, Qinghe', 'Feng, Li', 'Sun, Dongbo']",,,,
,PMC,Protecting children from maltreatment: A Canadian call to action,,PMC3887077,,,,,"MacMillan, Harriet L",,,,
,PMC,Therapeutic Targeting of Autophagy in Disease: Biology and Pharmacology,http://dx.doi.org/10.1124/pr.112.007120,PMC3799234,,,"Autophagy, a process of self-digestion of the cytoplasm and organelles through which cellular components are recycled for reuse or energy production, is an evolutionarily conserved response to metabolic stress found in eukaryotes from yeast to mammals. It is noteworthy that autophagy is also associated with various pathophysiologic conditions in which this cellular process plays either a cytoprotective or cytopathic role in response to a variety of stresses such as metabolic, inflammatory, neurodegenerative, and therapeutic stress. It is now generally believed that modulating the activity of autophagy through targeting specific regulatory molecules in the autophagy machinery may impact disease processes, thus autophagy may represent a new pharmacologic target for drug development and therapeutic intervention of various human disorders. Induction or inhibition of autophagy using small molecule compounds has shown promise in the treatment of diseases such as cancer. Depending on context, induction or suppression of autophagy may exert therapeutic effects via promoting either cell survival or death, two major events targeted by therapies for various disorders. A better understanding of the biology of autophagy and the pharmacology of autophagy modulators has the potential for facilitating the development of autophagy-based therapeutic interventions for several human diseases.",,"['Cheng, Yan', 'Ren, Xingcong', 'Hait, William N.', 'Yang, Jin-Ming']",,,,
,PMC,Plant as a plenteous reserve of lectin,http://dx.doi.org/10.4161/psb.26595,PMC4091380,,,"Lectins are clusters of glycoproteins of nonimmune foundation that combine specifically and reversibly to carbohydrates, mainly the sugar moiety of glycoconjugates, resulting in cell agglutination and precipitation of glycoconjugates. They are universally distributed in nature, being established in plants, fungi, viruses, bacteria, crustacea, insects, and animals, but leguminacae plants are rich source of lectins. The present review reveals the structure, biological properties, and application of plant lectins.",,"['Hivrale, AU', 'Ingale, AG']",,,,
,PMC,In This Issue,http://dx.doi.org/10.1073/iti4013110,PMC3791712,,,,,,,,,
,PMC,Health policy in Asia and the Pacific: Navigating local needs and global challenges,http://dx.doi.org/10.1002/app5.5,PMC3938190,,,"Asia and the Pacific are undergoing a remarkable economic transformation which is occurring at an exceptional pace. There is clear evidence of an equally rapid epidemiological transition in the region. This paper sets out the policy challenges of building healthy societies in the context of rapid economic change. The region’s location at the crossroads of contemporary globalization, resulting in intensified population mobility, large-scale trade and investment, and pressures to take collective action on shared problems, adds to the complexity of this task. The paper argues that health is integral to building stable and sustainable societies, and that there are opportunities to develop more holistic approaches that bring together hitherto separate policy spheres.",,"Lee, Kelley",,,,
,PMC,Elevated Viral Restriction Factor Levels in Cortical Blood Vessels in Schizophrenia,http://dx.doi.org/10.1016/j.biopsych.2013.09.019,PMC3969896,,,"BACKGROUND: Higher tissue transcript levels of immune-related markers, including the recently discovered viral restriction factor interferon-induced transmembrane protein (IFITM) which inhibits viral entry and replication, have been reported in the prefrontal cortex in schizophrenia. Interestingly, mouse models of neuroinflammation have higher IFITM levels and deficits in GABA-related markers that are similar to findings in schizophrenia, suggesting that a shared pathogenetic process may underlie diverse cortical pathology in the disorder. However, the cell types that overexpress IFITM mRNA in schizophrenia are unknown, and it is unclear whether higher IFITM mRNA levels are associated with lower GABA-related marker levels in the same schizophrenia subjects. METHODS: We used quantitative PCR and in situ hybridization with film and grain counting analyses to quantify IFITM mRNA levels in prefrontal cortex area 9 of 57 schizophrenia and 57 healthy comparison subjects and in antipsychotic-exposed monkeys. RESULTS: Quantitative PCR and in situ hybridization film analysis revealed markedly elevated IFITM mRNA levels (+114% and +117%, respectively) in prefrontal gray matter in schizophrenia. Interestingly, emulsion-dipped, Nissl-stained sections from schizophrenia and comparison subjects revealed IFITM mRNA expression in pia mater and blood vessels. IFITM grain density over blood vessels was 71% higher in schizophrenia. IFITM mRNA levels were negatively correlated with GABA-related mRNAs in the same schizophrenia subjects. CONCLUSIONS: The finding that schizophrenia subjects with higher IFITM mRNA levels in cortical blood vessels have greater disturbances in cortical GABA neurons suggests that these cell-type distinct pathological disturbances may be influenced by a shared upstream insult that involves immune activation.",,"['Siegel, Benjamin I.', 'Sengupta, Elizabeth J.', 'Edelson, Jessica R.', 'Lewis, David A.', 'Volk, David W.']",,,,
,PMC,"Design, Synthesis, and Bioevaluation of Viral 3C and 3C-Like Protease Inhibitors",http://dx.doi.org/10.1016/j.bmcl.2013.09.070,PMC3863581,,,"A class of tripeptidyl transition state inhibitors containing a P1 glutamine surrogate, a P2 leucine, and a P3 arylalanines, was found to potently inhibit Norwalk virus replication in enzyme and cell based assays. An array of warheads, including aldehyde, α-ketoamide, bisulfite adduct, and α-hydroxyphosphonate transition state mimic, was also investigated. Tripeptidyls 2 and 6 possess antiviral activities against noroviruses, human rhinovirus, severe acute respiratory syndrome coronavirus, and coronavirus 229E, suggesting a broad range of antiviral activities.",,"['Prior, Allan M.', 'Kim, Yunjeong', 'Weerasekara, Sahani', 'Moroze, Meghan', 'Alliston, Kevin R.', 'Uy, Roxanne Adeline Z.', 'Groutas, William C.', 'Chang, Kyeong-Ok', 'Hua, Duy H.']",,,,
,PMC,Vaccine-derived Mutation in Motif D of Poliovirus RNA-dependent RNA Polymerase Lowers Nucleotide Incorporation Fidelity,http://dx.doi.org/10.1074/jbc.M113.484428,PMC3820909,,,"All viral RNA-dependent RNA polymerases (RdRps) have a conserved structural element termed motif D. Studies of the RdRp from poliovirus (PV) have shown that a conformational change of motif D leads to efficient and faithful nucleotide addition by bringing Lys-359 into the active site where it serves as a general acid. The RdRp of the Sabin I vaccine strain has Thr-362 changed to Ile. Such a drastic change so close to Lys-359 might alter RdRp function and contribute in some way to the attenuated phenotype of Sabin type I. Here we present our characterization of the T362I RdRp. We find that the T362I RdRp exhibits a mutator phenotype in biochemical experiments in vitro. Using NMR, we show that this change in nucleotide incorporation fidelity correlates with a change in the structural dynamics of motif D. A recombinant PV expressing the T362I RdRp exhibits normal growth properties in cell culture but expresses a mutator phenotype in cells. For example, the T362I-containing PV is more sensitive to the mutagenic activity of ribavirin than wild-type PV. Interestingly, the T362I change was sufficient to cause a statistically significant reduction in viral virulence. Collectively, these studies suggest that residues of motif D can be targeted when changes in nucleotide incorporation fidelity are desired. Given the observation that fidelity mutants can serve as vaccine candidates, it may be possible to use engineering of motif D for this purpose.",,"['Liu, Xinran', 'Yang, Xiaorong', 'Lee, Cheri A.', 'Moustafa, Ibrahim M.', 'Smidansky, Eric D.', 'Lum, David', 'Arnold, Jamie J.', 'Cameron, Craig E.', 'Boehr, David D.']",,,,
,PMC,Identification of apolipoprotein D as a cardioprotective gene using a mouse model of lethal atherosclerotic coronary artery disease,http://dx.doi.org/10.1073/pnas.1315986110,PMC3801016,,,"Mice with homozygous null mutations in the HDL receptor (scavenger receptor class B, type I, or SR-BI) and apolipoprotein E (apoE) genes [SR-BI/apoE double KO (SR-BI(−/−)/apoE(−/−) or dKO) mice] spontaneously develop occlusive, atherosclerotic coronary artery disease (CAD) and die prematurely (50% mortality at 42 d of age). Using microarray mRNA expression profiling, we identified genes whose expression in the hearts of dKO mice changed substantially during disease progression [at 21 d of age (no CAD), 31 d of age (small myocardial infarctions), and 43 d of age (extensive myocardial infarctions) vs. CAD-free SR-BI(+/−)/apoE(−/−) controls]. Expression of most genes that increased >sixfold in dKO hearts at 43 d also increased after coronary artery ligation. We examined the influence and potential mechanism of action of apolipoprotein D (apoD) whose expression in dKO hearts increased 80-fold by 43 d. Analysis of ischemia/reperfusion-induced myocardial infarction in both apoD KO mice and wild-type mice with abnormally high plasma levels of apoD (adenovirus-mediated hepatic overexpression) established that apoD reduces myocardial infarction. There was a correlation of apoD’s ability to protect primary cultured rat cardiomyocytes from hypoxia/reoxygenation injury with its potent ability to inhibit oxidation in a standard antioxidation assay in vitro. We conclude that dKO mice represent a useful mouse model of CAD and apoD may be part of an intrinsic cardioprotective system, possibly as a consequence of its antioxidation activity.",,"['Tsukamoto, Kosuke', 'Mani, D. R.', 'Shi, Jianru', 'Zhang, Songwen', 'Haagensen, Darrow E.', 'Otsuka, Fumiyuki', 'Guan, Jian', 'Smith, Jonathan D.', 'Weng, Wei', 'Liao, Ronglih', 'Kolodgie, Frank D.', 'Virmani, Renu', 'Krieger, Monty']",,,,
,PMC,International Health Regulations (2005): public health event communications in the Western Pacific Region,http://dx.doi.org/10.5365/WPSAR.2013.4.3.003,PMC3854101,,,,,"['Fearnley, Emily', 'Ailan, Li']",,,,
,PMC,Implementing the International Health Regulations (2005) in the World Health Organization Western Pacific Region,http://dx.doi.org/10.5365/WPSAR.2013.4.3.004,PMC3854098,,,,,"Li, Ailan",,,,
,PMC,Innate immune response to arenaviral infection: a focus on the highly pathogenic New World hemorrhagic arenaviruses,http://dx.doi.org/10.1016/j.jmb.2013.09.028,PMC3864108,,,"Arenaviruses are enveloped, negative-stranded RNA viruses that belong to the family Arenaviridae. This diverse family can be further classified into OW (Old World) and NW (New World) arenaviruses based on their antigenicity, phylogeny, and geographical distribution. Many of the NW arenaviruses are highly pathogenic viruses that cause systemic human infections characterized by hemorrhagic fever and/or neurological manifestations, constituting public health problems in their endemic regions. NW arenavirus infection induces a variety of host innate immune responses, which could contribute to the viral pathogenesis and/or influence the final outcome of virus infection in vitro as well as in vivo. On the other hand, NW arenaviruses have also developed several strategies to counteract the host innate immune response. We will review current knowledge regarding the interplay between the host innate immune response and NW arenavirus infection in vitro and in vivo, with emphasis on viral-encoded proteins and their effect on the type I interferon response.",,"['Koma, Takaaki', 'Huang, Cheng', 'Kolokoltsova, Olga A', 'Brasier, Allan R', 'Paessler, Slobodan']",,,,
,PMC,Back to the future: recombinant polyclonal antibody therapeutics,http://dx.doi.org/10.1016/j.coche.2013.08.005,PMC3892273,,,"Antibody therapeutics are one of the fastest growing classes of pharmaceuticals, with an annual US market over $20 billion, developed to treat a variety of diseases including cancer, auto-immune and infectious diseases. Most are currently administered as a single molecule to treat a single disease, however there is mounting evidence that cocktails of multiple antibodies, each with a unique binding specificity and protective mechanism, may improve clinical efficacy. Here, we review progress in the development of oligoclonal combinations of antibodies to treat disease, focusing on identification of synergistic antibodies. We then discuss the application of modern antibody engineering technologies to produce highly potent antibody preparations, including oligoclonal antibody cocktails and truly recombinant polyclonal antibodies. Specific examples illustrating the synergy conferred by multiple antibodies will be provided for diseases caused by botulinum toxin, cancer and immune thrombocytopenia. The bioprocessing and regulatory options for these preparations will be discussed.",,"['Wang, Xian-zhe', 'Coljee, Vincent W.', 'Maynard, Jennifer A.']",,,,
,PMC,Interferon-induced Transmembrane Protein 3 Is a Type II Transmembrane Protein,http://dx.doi.org/10.1074/jbc.M113.514356,PMC3820858,,,"The interferon-induced transmembrane (IFITM) proteins are a family of small membrane proteins that inhibit the cellular entry of several genera of viruses. These proteins had been predicted to adopt a two-pass, type III transmembrane topology with an intracellular loop, two transmembrane helices (TM1 and TM2), and extracellular N and C termini. Recent work, however, supports an intramembrane topology for the helices with cytosolic orientation of both termini. Here we determined the topology of murine Ifitm3. We found that the N terminus of Ifitm3 could be stained by antibodies at the cell surface but that this conformation was cell type-dependent and represented a minority of the total plasma membrane pool. In contrast, the C terminus was readily accessible to antibodies at the cell surface and extracellular C termini comprised most or all of those present at the plasma membrane. The addition of a C-terminal KDEL endoplasmic reticulum retention motif to Ifitm3 resulted in sequestration of Ifitm3 in the ER, demonstrating an ER-luminal orientation of the C terminus. C-terminal, but not N-terminal, epitope tags were also degraded within lysosomes, consistent with their luminal orientation. Furthermore, epitope-tagged Ifitm3 TM2 functioned as a signal anchor sequence when expressed in isolation. Collectively, our results demonstrate a type II transmembrane topology for Ifitm3 and will provide insight into its interaction with potential targets and cofactors.",,"['Bailey, Charles C.', 'Kondur, Hema R.', 'Huang, I-Chueh', 'Farzan, Michael']",,,,
,PMC,IFITMs restrict the replication of multiple pathogenic viruses,http://dx.doi.org/10.1016/j.jmb.2013.09.024,PMC4121887,,,"The IFITM family of proteins inhibit a growing number of pathogenic viruses, among them influenza A virus, dengue virus, hepatitis C virus, and Ebola virus. This review covers recent developments in our understanding of the IFITM’s molecular determinants, potential mechanisms of action, and impact on pathogenesis.",,"['Perreira, Jill M.', 'Chin, Christopher R.', 'Feeley, Eric M.', 'Brass, Abraham L.']",,,,
,PMC,Outbreak of Variant Influenza A(H3N2) Virus in the United States,http://dx.doi.org/10.1093/cid/cit649,PMC5733625,,,"BACKGROUND: Variant influenza virus infections are rare but may have pandemic potential if person-to-person transmission is efficient. We describe the epidemiology of a multistate outbreak of an influenza A(H3N2) variant virus (H3N2v) first identified in 2011. METHODS: We identified laboratory-confirmed cases of H3N2v and used a standard case report form to characterize illness and exposures. We considered illness to result from person-to-person H3N2v transmission if swine contact was not identified within 4 days prior to illness onset. RESULTS: From 9 July to 7 September 2012, we identified 306 cases of H3N2v in 10 states. The median age of all patients was 7 years. Commonly reported signs and symptoms included fever (98%), cough (85%), and fatigue (83%). Sixteen patients (5.2%) were hospitalized, and 1 fatal case was identified. The majority of those infected reported agricultural fair attendance (93%) and/or contact with swine (95%) prior to illness. We identified 15 cases of possible person-to-person transmission of H3N2v. Viruses recovered from patients were 93%–100% identical and similar to viruses recovered from previous cases of H3N2v. All H3N2v viruses examined were susceptible to oseltamivir and zanamivir and resistant to adamantane antiviral medications. CONCLUSIONS: In a large outbreak of variant influenza, the majority of infected persons reported exposures, suggesting that swine contact at an agricultural fair was a risk for H3N2v infection. We identified limited person-to-person H3N2v virus transmission, but found no evidence of efficient or sustained person-to-person transmission. Fair managers and attendees should be aware of the risk of swine-to-human transmission of influenza viruses in these settings.",,"['Jhung, Michael A.', 'Epperson, Scott', 'Biggerstaff, Matthew', 'Allen, Donna', 'Balish, Amanda', 'Barnes, Nathelia', 'Beaudoin, Amanda', 'Berman, LaShondra', 'Bidol, Sally', 'Blanton, Lenee', 'Blythe, David', 'Brammer, Lynnette', 'D’Mello, Tiffany', 'Danila, Richard', 'Davis, William', 'de Fijter, Sietske', 'DiOrio, Mary', 'Durand, Lizette O.', 'Emery, Shannon', 'Fowler, Brian', 'Garten, Rebecca', 'Grant, Yoran', 'Greenbaum, Adena', 'Gubareva, Larisa', 'Havers, Fiona', 'Haupt, Thomas', 'House, Jennifer', 'Ibrahim, Sherif', 'Jiang, Victoria', 'Jain, Seema', 'Jernigan, Daniel', 'Kazmierczak, James', 'Klimov, Alexander', 'Lindstrom, Stephen', 'Longenberger, Allison', 'Lucas, Paul', 'Lynfield, Ruth', 'McMorrow, Meredith', 'Moll, Maria', 'Morin, Craig', 'Ostroff, Stephen', 'Page, Shannon L.', 'Park, Sarah Y.', 'Peters, Susan', 'Quinn, Celia', 'Reed, Carrie', 'Richards, Shawn', 'Scheftel, Joni', 'Simwale, Owen', 'Shu, Bo', 'Soyemi, Kenneth', 'Stauffer, Jill', 'Steffens, Craig', 'Su, Su', 'Torso, Lauren', 'Uyeki, Timothy M.', 'Vetter, Sara', 'Villanueva, Julie', 'Wong, Karen K.', 'Shaw, Michael', 'Bresee, Joseph S.', 'Cox, Nancy', 'Finelli, Lyn']",,,,
,PMC,"Respiratory Syncytial Virus Lower Respiratory Disease in Hematopoietic Cell Transplant Recipients: Viral RNA Detection in Blood, Antiviral Treatment, and Clinical Outcomes",http://dx.doi.org/10.1093/cid/cit639,PMC3840404,,,"Background. Respiratory syncytial virus (RSV) pneumonia after hematopoietic cell transplant (HCT) is associated with severe morbidity. Although RSV RNA has been detected in serum from patients with RSV lower respiratory disease (LRD) after HCT, the association with clinical outcomes has not been well established in multivariable models. Additionally, the role of antiviral treatment in HCT recipients has not been previously analyzed in multivariable models. Methods. We retrospectively identified HCT recipients with virologically confirmed RSV LRD and tested stored plasma/serum samples by quantitative reverse transcription polymerase chain reaction for RSV RNA. Risk factors for RSV RNA detection and the impact of RSV RNA in serum and antiviral therapy on outcomes were analyzed using multivariable Cox models. Results. RSV RNA was detected in plasma or serum from 28 of 92 (30%) patients at a median of 24.5 days following HCT and 2 days following LRD. In multivariable models, neutropenia, monocytopenia, thrombocytopenia, and mechanical ventilation increased the risk of plasma/serum RSV RNA detection; lymphopenia and steroid use did not. RSV RNA detection increased the risk of overall mortality in multivariable models (adjusted hazard ratio [aHR], 2.09 [P = .02]), whereas treatment with aerosolized ribavirin decreased the risk of overall mortality and pulmonary death (aHR, 0.33 [P = .001] and aHR 0.31 [P = .003], respectively). Conclusions. RSV RNA detection in plasma or serum may be a marker for lung injury and poor outcomes in HCT recipients with RSV LRD. Treatment with aerosolized ribavirin appeared to be protective against overall and pulmonary mortality.",,"['Waghmare, Alpana', 'Campbell, Angela P.', 'Xie, Hu', 'Seo, Sachiko', 'Kuypers, Jane', 'Leisenring, Wendy', 'Jerome, Keith R.', 'Englund, Janet A.', 'Boeckh, Michael']",,,,
,PMC,Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques,http://dx.doi.org/10.1073/pnas.1310744110,PMC3799368,,,"In 2012, a novel betacoronavirus, designated Middle East respiratory syndrome coronavirus or MERS-CoV and associated with severe respiratory disease in humans, emerged in the Arabian Peninsula. To date, 108 human cases have been reported, including cases of human-to-human transmission. The availability of an animal disease model is essential for understanding pathogenesis and developing effective countermeasures. Upon a combination of intratracheal, ocular, oral, and intranasal inoculation with 7 × 10(6) 50% tissue culture infectious dose of the MERS-CoV isolate HCoV-EMC/2012, rhesus macaques developed a transient lower respiratory tract infection. Clinical signs, virus shedding, virus replication in respiratory tissues, gene expression, and cytokine and chemokine profiles peaked early in infection and decreased over time. MERS-CoV caused a multifocal, mild to marked interstitial pneumonia, with virus replication occurring mainly in alveolar pneumocytes. This tropism of MERS-CoV for the lower respiratory tract may explain the severity of the disease observed in humans and the, up to now, limited human-to-human transmission.",,"['de Wit, Emmie', 'Rasmussen, Angela L.', 'Falzarano, Darryl', 'Bushmaker, Trenton', 'Feldmann, Friederike', 'Brining, Douglas L.', 'Fischer, Elizabeth R.', 'Martellaro, Cynthia', 'Okumura, Atsushi', 'Chang, Jean', 'Scott, Dana', 'Benecke, Arndt G.', 'Katze, Michael G.', 'Feldmann, Heinz', 'Munster, Vincent J.']",,,,
,PMC,Monocyte Chemoattractant Protein-1 and Blood-Brain Barrier,http://dx.doi.org/10.1007/s00018-013-1459-1,PMC3946874,,,"Blood-Brain Barrier (BBB) is a dynamic structure that maintains the homeostasis of the brain and thus proper neurological functions. BBB compromise has been found in many pathological conditions, including neuroinflammation. Monocyte chemoattractant protein-1 (MCP1), a chemokine that is transiently and significantly up-regulated during inflammation, is able to disrupt the integrity of BBB and modulate the progression of various diseases, including excitotoxic injury and hemorrhage. In this review, we first introduce the biochemistry and biology of MCP1, and then summarize the effects of MCP1 on BBB integrity as well as individual BBB components.",,"['Yao, Yao', 'Tsirka, Stella E.']",,,,
,PMC,Intraspinal transplantation of mouse and human neural precursor cells,http://dx.doi.org/10.1002/9780470151808.sc02d16s26,PMC3920297,,,"This unit describes the preparation and transplantation of human neural precursor cells (hNPCs) and mouse neural precursor cells (mNPCs) into the thoracic region of the mouse spinal cord. The techniques in this unit also describe how to prepare the mouse for surgery by performing a laminectomy to expose the spinal cord for transplantation. Here we show NPCs genetically labeled with eGFP transplanted into the spinal cord of a mouse following viralmediated demyelination can efficiently be detected via eGFP expression. Transplantation of these cells into the spinal cord is an efficacious way to determine their effects in neurological disorders such as multiple sclerosis, Alzheimer's disease, and spinal cord injury.",,"['Weinger, Jason G.', 'Chen, Lu', 'Coleman, Ronald', 'Leang, Ronika', 'Plaisted, Warren C.', 'Loring, Jeanne F.', 'Lane, Thomas E.']",,,,
,PMC,The minimalist architectures of viroporins and their therapeutic implications,http://dx.doi.org/10.1016/j.bbamem.2013.09.004,PMC3943691,,,"Many viral genomes encode small, integral membrane proteins that form homo-oligomeric channels in membrane, and they transport protons, cations, and other molecules across the membrane barrier to aid various steps of viral entry and maturation. These viral proteins, collectively named viroporins, are crucial for viral pathogenicity. In the past five years, structures obtained by nuclear magnetic resonance (NMR), X-ray crystallography, and electron microscopy (EM) showed that viroporins often adopt minimalist architectures to achieve their functions. A number of small molecules have been identified to interfere with their channel activity and thereby inhibit viral infection, making viroporins potential drug targets for therapeutic intervention. The known architectures and inhibition mechanisms of viroporins differ significantly from each other, but some common principles are shared between them. This review article summarizes the recent developments in the structural investigation of viroporins and their inhibition by antiviral compounds.",,"['OuYang, Bo', 'Chou, James J.']",,,,
,PMC,Application of real time RT-PCR for the genetic homogeneity and stability tests of the seed candidates for live attenuated influenza vaccine production,http://dx.doi.org/10.1016/j.jviromet.2013.09.003,PMC4607041,,,"Development and improvement of quality control tests for live attenuated vaccines are a high priority because of safety concerns. Live attenuated influenza vaccine (LAIV) viruses are 6:2 reassortants containing the hemagglutinin (HA) and neuraminidase (NA) gene segments from circulating influenza viruses to induce protective immune responses, and the six internal gene segments from a cold-adapted Master Donor Virus (MDV). LAIV candidate viruses for the 2012–2013 seasons, A/Victoria/361/2011-CDC-LV1 (LV1) and B/Texas/06/2011-CDC-LV2B (LV2B), were created by classical reassortment of A/Victoria/361/2011 and MDV-A A/Leningrad/134/17/57 (H2N2) or B/Texas/06/2011 and MDV-B B/USSR/60/69. In an attempt to provide better identity and stability testing for quality control of LV1 and LV2B, sensitive real-time RT-PCR assays (rRT-PCR) were developed to detect the presence of undesired gene segments (HA and NA from MDV and the six internal genes from the seasonal influenza viruses). The sensitivity of rRT-PCR assays designed for each gene segment ranged from 0.08 to 0.8 EID(50) (50% of Egg Infectious Dose) per reaction for the detection of undesired genes in LV1 and from 0.1 to 1 EID(50) per reaction for the detection of undesired genes in LV2B. No undesired genes were detected either before or after five passages of LV1 or LV2B in eggs. The complete genome sequencing of LV1 and LV2B confirmed the results of rRT-PCR, demonstrating the utility of the new rRT-PCR assays to provide the evidence for the homogeneity of the prepared vaccine candidate.",,"['Shcherbik, Svetlana', 'Sergent, Sheila B.', 'Davis, William G.', 'Shu, Bo', 'Barnes, John', 'Kiseleva, Irina', 'Larionova, Natalie', 'Klimov, Alexander', 'Bousse, Tatiana']",,,,
,PMC,Architectural Organization of the Metabolic Regulatory Enzyme Ghrelin O-Acyltransferase,http://dx.doi.org/10.1074/jbc.M113.510313,PMC3820860,,,"Ghrelin O-acyltransferase (GOAT) is a polytopic integral membrane protein required for activation of ghrelin, a secreted metabolism-regulating peptide hormone. Although GOAT is a potential therapeutic target for the treatment of obesity and diabetes and plays a key role in other physiologic processes, little is known about its structure or mechanism. GOAT is a member of the membrane-bound O-acyltransferase (MBOAT) family, a group of polytopic integral membrane proteins involved in lipid-biosynthetic and lipid-signaling reactions from prokaryotes to humans. Here we use phylogeny and a variety of bioinformatic tools to predict the topology of GOAT. Using selective permeabilization indirect immunofluorescence microscopy in combination with glycosylation shift immunoblotting, we demonstrate that GOAT contains 11 transmembrane helices and one reentrant loop. Development of the V5Glyc tag, a novel, small, and sensitive dual topology reporter, facilitated these experiments. The MBOAT family invariant residue His-338 is in the ER lumen, consistent with other family members, but conserved Asn-307 is cytosolic, making it unlikely that both are involved in catalysis. Photocross-linking of synthetic ghrelin analogs and inhibitors demonstrates binding to the C-terminal region of GOAT, consistent with a role of His-338 in the active site. This knowledge of GOAT architecture is important for a deeper understanding of the mechanism of GOAT and other MBOATs and could ultimately advance the discovery of selective inhibitors for these enzymes.",,"['Taylor, Martin S.', 'Ruch, Travis R.', 'Hsiao, Po-Yuan', 'Hwang, Yousang', 'Zhang, Pingfeng', 'Dai, Lixin', 'Huang, Cheng Ran Lisa', 'Berndsen, Christopher E.', 'Kim, Min-Sik', 'Pandey, Akhilesh', 'Wolberger, Cynthia', 'Marmorstein, Ronen', 'Machamer, Carolyn', 'Boeke, Jef D.', 'Cole, Philip A.']",,,,
,PMC,Structural and Inhibitor Studies of Norovirus 3C-like Proteases,http://dx.doi.org/10.1016/j.virusres.2013.09.008,PMC3840063,,,"Noroviruses have a single-stranded, positive sense 7–8 kb RNA genome, which encodes a polyprotein precursor processed by a virus-encoded 3C-like cysteine protease (3CLpro) to generate mature non-structural proteins. Because processing of the polyprotein is essential for virus replication, norovirus 3CLpro has been targeted for the discovery of anti-norovirus small molecule therapeutics. Thus, we performed functional, structural and inhibition studies of norovirus 3CLpro with fluorescence resonance energy transfer (FRET) assay, X-ray crystallography, and NMR spectroscopy with a synthetic protease inhibitor. Three 3CLpro from Norwalk virus (NV, genogroup I), MD145 (genogroup II) and murine norovirus-1 (MNV-1, genogroup V) were optimized for a FRET assay, and compared for the inhibitory activities of a synthetic protease inhibitor (GC376). The apo 3D structures of NV 3CLpro determined with X-ray crystallography and NMR spectroscopy were further analyzed. In addition, the binding mode of NV 3CLpro-GC376 was compared with X-ray crystallography and NMR spectroscopy. The results of this report provide insight into the interaction of NV 3CLpro with substrate/inhibitor for better understanding of the enzyme and antiviral drug development.",,"['Takahashi, Daisuke', 'Kim, Yunjeong', 'Lovell, Scott', 'Prakash, Om', 'Groutas, William C', 'Chang, Kyeong-Ok']",,,,
,PMC,Jun Activation Domain-binding Protein 1 (JAB1) Is Required for the Optimal Response to Interferons,http://dx.doi.org/10.1074/jbc.M113.485847,PMC3829410,,,"Degradation of IFN receptor (IFNR) protein is one of the mechanisms to limit the extent of cellular responses to interferons. Tyrosine kinase 2 (TYK2), a JAK family kinase, has been reported to bind to and stabilize IFNR, indicating that TYK2 is a fundamental component of IFNR complex. Herein, we identified Jun activation domain-binding protein 1 (JAB1) as a new TYK2 binding partner and investigated its role in the regulation of IFN responses. siRNA knockdown of JAB1 resulted in suppression of IFN-induced phosphorylation of STAT proteins and their transcriptional activation. Importantly, JAB1 knockdown induced the activation of SCF ubiquitin ligase complex containing Cullin 1 (CUL1), as judged by the enhancement of covalent modification of CUL1 with the ubiquitin-like protein NEDD8, and markedly reduced the basal protein level of IFNR. In contrast, NEDD8 knockdown or inhibition of NEDD8 modification by NEDD8-activating enzyme inhibitor resulted in increased IFNR protein concomitantly with a reduction of NEDD8-modified CUL1. Furthermore, NEDD8-activating enzyme inhibitor treatment enhanced the susceptibility to IFN-α in HeLa cells. These data suggest that the NEDD8 modification pathway is involved in the proteolysis of IFNR and that JAB1 acts as a positive regulator of IFN responses by stabilizing IFNR through antagonizing the NEDD8 pathway.",,"['Muromoto, Ryuta', 'Nakajima, Maiko', 'Hirashima, Koki', 'Hirao, Toru', 'Kon, Shigeyuki', 'Shimoda, Kazuya', 'Oritani, Kenji', 'Matsuda, Tadashi']",,,,
,PMC,Bats carry pathogenic hepadnaviruses antigenically related to hepatitis B virus and capable of infecting human hepatocytes,http://dx.doi.org/10.1073/pnas.1308049110,PMC3791787,,,"The hepatitis B virus (HBV), family Hepadnaviridae, is one of most relevant human pathogens. HBV origins are enigmatic, and no zoonotic reservoirs are known. Here, we screened 3,080 specimens from 54 bat species representing 11 bat families for hepadnaviral DNA. Ten specimens (0.3%) from Panama and Gabon yielded unique hepadnaviruses in coancestral relation to HBV. Full genome sequencing allowed classification as three putative orthohepadnavirus species based on genome lengths (3,149–3,377 nt), presence of middle HBV surface and X-protein genes, and sequence distance criteria. Hepatic tropism in bats was shown by quantitative PCR and in situ hybridization. Infected livers showed histopathologic changes compatible with hepatitis. Human hepatocytes transfected with all three bat viruses cross-reacted with sera against the HBV core protein, concordant with the phylogenetic relatedness of these hepadnaviruses and HBV. One virus from Uroderma bilobatum, the tent-making bat, cross-reacted with monoclonal antibodies against the HBV antigenicity determining S domain. Up to 18.4% of bat sera contained antibodies against bat hepadnaviruses. Infectious clones were generated to study all three viruses in detail. Hepatitis D virus particles pseudotyped with surface proteins of U. bilobatum HBV, but neither of the other two viruses could infect primary human and Tupaia belangeri hepatocytes. Hepatocyte infection occurred through the human HBV receptor sodium taurocholate cotransporting polypeptide but could not be neutralized by sera from vaccinated humans. Antihepadnaviral treatment using an approved reverse transcriptase inhibitor blocked replication of all bat hepadnaviruses. Our data suggest that bats may have been ancestral sources of primate hepadnaviruses. The observed zoonotic potential might affect concepts aimed at eradicating HBV.",,"['Drexler, Jan Felix', 'Geipel, Andreas', 'König, Alexander', 'Corman, Victor M.', 'van Riel, Debby', 'Leijten, Lonneke M.', 'Bremer, Corinna M.', 'Rasche, Andrea', 'Cottontail, Veronika M.', 'Maganga, Gael D.', 'Schlegel, Mathias', 'Müller, Marcel A.', 'Adam, Alexander', 'Klose, Stefan M.', 'Borges Carneiro, Aroldo José', 'Stöcker, Andreas', 'Franke, Carlos Roberto', 'Gloza-Rausch, Florian', 'Geyer, Joachim', 'Annan, Augustina', 'Adu-Sarkodie, Yaw', 'Oppong, Samuel', 'Binger, Tabea', 'Vallo, Peter', 'Tschapka, Marco', 'Ulrich, Rainer G.', 'Gerlich, Wolfram H.', 'Leroy, Eric', 'Kuiken, Thijs', 'Glebe, Dieter', 'Drosten, Christian']",,,,
,PMC,Reverse genetics with a full-length infectious cDNA of the Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1073/pnas.1311542110,PMC3791741,,,"Severe acute respiratory syndrome with high mortality rates (∼50%) is associated with a novel group 2c betacoronavirus designated Middle East respiratory syndrome coronavirus (MERS-CoV). We synthesized a panel of contiguous cDNAs that spanned the entire genome. Following contig assembly into genome-length cDNA, transfected full-length transcripts recovered several recombinant viruses (rMERS-CoV) that contained the expected marker mutations inserted into the component clones. Because the wild-type MERS-CoV contains a tissue culture-adapted T1015N mutation in the S glycoprotein, rMERS-CoV replicated ∼0.5 log less efficiently than wild-type virus. In addition, we ablated expression of the accessory protein ORF5 (rMERS•ORF5) and replaced it with tomato red fluorescent protein (rMERS-RFP) or deleted the entire ORF3, 4, and 5 accessory cluster (rMERS-ΔORF3–5). Recombinant rMERS-CoV, rMERS-CoV•ORF5, and MERS-CoV-RFP replicated to high titers, whereas MERS-ΔORF3–5 showed 1–1.5 logs reduced titer compared with rMERS-CoV. Northern blot analyses confirmed the associated molecular changes in the recombinant viruses, and sequence analysis demonstrated that RFP was expressed from the appropriate consensus sequence AACGAA. We further show dipeptidyl peptidase 4 expression, MERS-CoV replication, and RNA and protein synthesis in human airway epithelial cell cultures, primary lung fibroblasts, primary lung microvascular endothelial cells, and primary alveolar type II pneumocytes, demonstrating a much broader tissue tropism than severe acute respiratory syndrome coronavirus. The availability of a MERS-CoV molecular clone, as well as recombinant viruses expressing indicator proteins, will allow for high-throughput testing of therapeutic compounds and provide a genetic platform for studying gene function and the rational design of live virus vaccines.",,"['Scobey, Trevor', 'Yount, Boyd L.', 'Sims, Amy C.', 'Donaldson, Eric F.', 'Agnihothram, Sudhakar S.', 'Menachery, Vineet D.', 'Graham, Rachel L.', 'Swanstrom, Jesica', 'Bove, Peter F.', 'Kim, Jeeho D.', 'Grego, Sonia', 'Randell, Scott H.', 'Baric, Ralph S.']",,,,
,PMC,A New Framework and Software to Estimate Time-Varying Reproduction Numbers During Epidemics,http://dx.doi.org/10.1093/aje/kwt133,PMC3816335,,,"The quantification of transmissibility during epidemics is essential to designing and adjusting public health responses. Transmissibility can be measured by the reproduction number R, the average number of secondary cases caused by an infected individual. Several methods have been proposed to estimate R over the course of an epidemic; however, they are usually difficult to implement for people without a strong background in statistical modeling. Here, we present a ready-to-use tool for estimating R from incidence time series, which is implemented in popular software including Microsoft Excel (Microsoft Corporation, Redmond, Washington). This tool produces novel, statistically robust analytical estimates of R and incorporates uncertainty in the distribution of the serial interval (the time between the onset of symptoms in a primary case and the onset of symptoms in secondary cases). We applied the method to 5 historical outbreaks; the resulting estimates of R are consistent with those presented in the literature. This tool should help epidemiologists quantify temporal changes in the transmission intensity of future epidemics by using surveillance data.",,"['Cori, Anne', 'Ferguson, Neil M.', 'Fraser, Christophe', 'Cauchemez, Simon']",,,,
,PMC,Metadata-driven Comparative Analysis Tool for Sequences (meta-CATS): an Automated Process for Identifying Significant Sequence Variations that Correlate with Virus Attributes,http://dx.doi.org/10.1016/j.virol.2013.08.021,PMC5040469,,,"The Virus Pathogen Resource (ViPR; www.viprbrc.org) and Influenza Research Database (IRD; www.fludb.org) have developed a metadata-driven Comparative Analysis Tool for Sequences (meta-CATS), which performs statistical comparative analyses of nucleotide and amino acid sequence data to identify correlations between sequence variations and virus attributes (metadata). Meta-CATS guides users through: selecting a set of nucleotide or protein sequences; dividing them into multiple groups based on any associated metadata attribute (e.g. isolation location, host species); performing a statistical test at each aligned position; and identifying all residues that significantly differ between the groups. As proofs of concept, we have used meta-CATS to identify sequence biomarkers associated with dengue viruses isolated from different hemispheres, and to identify variations in the NS1 protein that are unique to each of the 4 dengue serotypes. Meta-CATS is made freely available to virology researchers to identify genotype-phenotype correlations for development of improved vaccines, diagnostics, and therapeutics.",,"['Pickett, BE', 'Liu, M', 'Sadat, EL', 'Squires, RB', 'Noronha, JM', 'He, S', 'Jen, W', 'Zaremba, S', 'Gu, Z', 'Zhou, L', 'Larsen, CN', 'Bosch, I', 'Gehrke, L', 'McGee, M', 'Klem, EB', 'Scheuermann, RH']",,,,
,PMC,HINCUTs in cancer: hypoxia-induced noncoding ultraconserved transcripts,http://dx.doi.org/10.1038/cdd.2013.119,PMC3824588,,,"Recent data have linked hypoxia, a classic feature of the tumor microenvironment, to the function of specific microRNAs (miRNAs); however, whether hypoxia affects other types of noncoding transcripts is currently unknown. Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs). Interestingly, several hypoxia-upregulated T-UCRs, henceforth named ‘hypoxia-induced noncoding ultraconserved transcripts' (HINCUTs), are also overexpressed in clinical samples from colon cancer patients. We show that these T-UCRs are predominantly nuclear and that the hypoxia-inducible factor (HIF) is at least partly responsible for the induction of several members of this group. One specific HINCUT, uc.475 (or HINCUT-1) is part of a retained intron of the host protein-coding gene, O-linked N-acetylglucosamine transferase, which is overexpressed in epithelial cancer types. Consistent with the hypothesis that T-UCRs have important function in tumor formation, HINCUT-1 supports cell proliferation specifically under hypoxic conditions and may be critical for optimal O-GlcNAcylation of proteins when oxygen tension is limiting. Our data gives a first glimpse of a novel functional hypoxic network comprising protein-coding transcripts and noncoding RNAs (ncRNAs) from the T-UCRs category.",,"['Ferdin, J', 'Nishida, N', 'Wu, X', 'Nicoloso, M S', 'Shah, M Y', 'Devlin, C', 'Ling, H', 'Shimizu, M', 'Kumar, K', 'Cortez, M A', 'Ferracin, M', 'Bi, Y', 'Yang, D', 'Czerniak, B', 'Zhang, W', 'Schmittgen, T D', 'Voorhoeve, M P', 'Reginato, M J', 'Negrini, M', 'Davuluri, R V', 'Kunej, T', 'Ivan, M', 'Calin, G A']",,,,
,PMC,Comparative Evaluation of Commercially Available Manual and Automated Nucleic Acid Extraction Methods for Rotavirus RNA Detection in Stool,http://dx.doi.org/10.1016/j.jviromet.2013.08.023,PMC4603280,,,"Rotaviruses are a major cause of viral gastroenteritis in children. For accurate and sensitive detection of rotavirus RNA from stool samples by reverse transcription-polymerase chain reaction (RT-PCR), the extraction process must be robust. However, some extraction methods may not remove the strong RT-PCR inhibitors known to be present in stool samples. The objective of this study was to evaluate and compare the performance of six extraction methods used commonly for extraction of rotavirus RNA from stool, which have never been formally evaluated: the MagNA Pure Compact, KingFisher Flex and NucliSENS® easyMAG® instruments, the NucliSENS® miniMAG® semi-automated system, and two manual purification kits, the QIAamp Viral RNA kit and a modified RNaid® kit. Using each method, total nucleic acid or RNA was extracted from eight rotavirus-positive stool samples with enzyme immunoassay optical density (EIA OD) values ranging from 0.176 to 3.098. Extracts prepared using the MagNA Pure Compact instrument yielded the most consistent results by qRT-PCR and conventional RT-PCR. When extracts prepared from a dilution series were extracted by the 6 methods and tested, rotavirus RNA was detected in all samples by qRT-PCR but by conventional RT-PCR testing, only the MagNA Pure Compact and KingFisher Flex extracts were positive in all cases. RT-PCR inhibitors were detected in extracts produced with the QIAamp Viral RNA Mini kit. The findings of this study should prove useful for selection of extraction methods to be incorporated into future rotavirus detection and genotyping protocols.",,"['Esona, Mathew D.', 'McDonald, Sharla', 'Kamili, Shifaq', 'Kerin, Tara', 'Gautam, Rashi', 'Bowen, Michael D.']",,,,
,PMC,Toll-like receptor 3 in viral pathogenesis: friend or foe?,http://dx.doi.org/10.1111/imm.12143,PMC3784162,,,"Viral infections frequently induce acute and chronic inflammatory diseases, yet the contribution of the innate immune response to a detrimental host response remains poorly understood. In virus-infected cells, double-stranded RNA (dsRNA) is generated as an intermediate during viral replication. Cell necrosis (and the release of endogenous dsRNA) is a common event during both sterile and infectious inflammatory processes. The discovery of Toll-like receptor 3 (TLR3) as an interferon-inducing dsRNA sensor led to the assumption that TLR3 was the master sentinel against viral infections. This simplistic view has been challenged by the discovery of at least three members of the DExd/H-box helicase cytosolic sensors of dsRNA that share with TLR3 the Toll–interleukin-1 receptor (TIR) -adapter molecule TIR domain-containing adaptor protein interferon-β (TRIF) for downstream type I interferon signalling. Data are conflicting on the role of TLR3 in protective immunity against viruses in the mouse model. Varying susceptibility to infection and disease outcomes have been reported in TLR3-immunodeficient mice. Surprisingly, the susceptibility to develop herpes simplex virus-1 encephalitis in humans with inborn defects of the TLR3 pathway varies, and TLR3-deficient humans do not show increased susceptibility to other viral infections. Therefore, a current challenge is to understand the protective versus pathogenic contribution of TLR3 in viral infections. We review recent advances in the identification of TLR3-signalling pathways, endogenous and virus-induced negative regulators of the TLR3 cascade, and discuss the protective versus pathogenic role of TLR3 in viral pathogenesis.",,"['Perales-Linares, Renzo', 'Navas-Martin, Sonia']",,,,
,PMC,Isolation of human monoclonal antibodies from peripheral blood B cells,http://dx.doi.org/10.1038/nprot.2013.117,PMC4844175,,,"Isolation of monoclonal antibodies is an important technique for understanding the specificities and characteristics of antibodies that underlie the humoral immune response to a given antigen. Here we describe a technique for isolating monoclonal antibodies from human peripheral blood mononuclear cells. The protocol includes strategies for the isolation of switch-memory B cells from peripheral blood, the culture of B cells, the removal of the supernatant for screening and the lysis of B cells in preparation for immunoglobulin heavy-chain and light-chain amplification and cloning. We have observed that the addition of cytokines IL-2, IL-21 and irradiated 3T3-msCD40L feeder cells can successfully stimulate switch-memory B cells to produce high concentrations of IgG in the supernatant. The supernatant may then be screened by appropriate assays for binding or for other functions. This protocol can be completed in 2 weeks. It is adaptable to use in other species and enables the efficient isolation of antibodies with a desired functional characteristic without prior knowledge of specificity.",,"['Huang, Jinghe', 'Doria-Rose, Nicole A', 'Longo, Nancy S', 'Laub, Leo', 'Lin, Chien-Li', 'Turk, Ellen', 'Kang, Byong H', 'Migueles, Stephen A', 'Bailer, Robert T', 'Mascola, John R', 'Connors, Mark']",,,,
,PMC,"Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: identification of ML300 and non-covalent nanomolar inhibitors with an induced-fit binding",http://dx.doi.org/10.1016/j.bmcl.2013.08.112,PMC3878165,,,"Herein we report the discovery and SAR of a novel series of SARS-CoV 3CLpro inhibitors identified through the NIH Molecular Libraries Probe Production Centers Network (MLPCN). In addition to ML188, ML300 represents the second probe declared for 3CLpro from this collaborative effort. The X-ray structure of SARS-CoV 3CLpro bound with a ML300 analog highlights a unique induced-fit reorganization of the S(2)-S(4) binding pockets leading to the first sub-micromolar non-covalent 3CLpro inhibitors retaining a single amide bond.",,"['Turlington, Mark', 'Chun, Aspen', 'Tomar, Sakshi', 'Eggler, Aimee', 'Grum-Tokars, Valerie', 'Jacobs, Jon', 'Daniels, J. Scott', 'Dawson, Eric', 'Saldanha, Adrian', 'Chase, Peter', 'Baez-Santos, Yahira M.', 'Lindsley, Craig W.', 'Hodder, Peter', 'Mesecar, Andrew', 'Stauffer, Shaun R.']",,,,
,PMC,Brain ACE2 shedding contributes to the development of neurogenic hypertension,http://dx.doi.org/10.1161/CIRCRESAHA.113.301811,PMC4479408,,,"RATIONALE: Over-activity of the brain Renin Angiotensin System (RAS) is a major contributor to neurogenic hypertension. While over-expression of Angiotensin-Converting Enzyme type 2 (ACE2) has been shown to be beneficial in reducing hypertension by transforming Angiotensin (Ang)-II into Ang-(1-7), several groups have reported decreased brain ACE2 expression and activity during the development of hypertension. OBJECTIVE: We hypothesized that ADAM17-mediated ACE2 shedding results in decreased membrane-bound ACE2 in the brain, thus promoting the development of neurogenic hypertension. METHODS AND RESULTS: To test this hypothesis, we used the DOCA-salt model of neurogenic hypertension in non-transgenic (NT) and syn-hACE2 mice over-expressing ACE2 in neurons. DOCA-salt treatment in NT mice led to significant increases in blood pressure, hypothalamic Ang-II levels, inflammation, impaired baroreflex sensitivity, autonomic dysfunction, as well as decreased hypothalamic ACE2 activity and expression, while these changes were blunted or prevented in syn-hACE2 mice. In addition, reduction of ACE2 expression and activity in the brain paralleled a rise in ACE2 activity in the cerebrospinal fluid of NT mice following DOCA-salt treatment and was accompanied by enhanced ADAM17 expression and activity in the hypothalamus. Chronic knockdown of ADAM17 in the brain blunted the development of hypertension and restored ACE2 activity and baroreflex function. CONCLUSIONS: Our data provide the first evidence that ADAM17-mediated shedding impairs brain ACE2 compensatory activity, thus contributing to the development of neurogenic hypertension.",,"['Xia, Huijing', 'Sriramula, Srinivas', 'Chhabra, Kavaljit H.', 'Lazartigues, Eric']",,,,
,PMC,"Multiple antigenic peptide (MAP): a synthetic peptide dendrimer for diagnostic, antiviral and vaccine strategies for emerging and re-emerging viral diseases",http://dx.doi.org/10.1007/s13337-013-0162-z,PMC3832690,,,"The peptide dendrimer provides novel strategies for various biological applications. Assembling of peptide in macromolecular structure is expected to give rational models as drugs, their delivery and diagnostic reagents. Improved understanding of virus structure and their molecular interactions with ligands have paved the way for treatment and control of emerging and re-emerging viral diseases. This review presents a brief account of a synthetic peptide dendrimer used for diagnostic, therapeutic and prophylactic applications. The designs comprise of multiple antigenic peptides which are being used as alternate synthetic antigens for different viruses.",,"['Joshi, Vinay Ganeshrao', 'Dighe, Vikas D.', 'Thakuria, Dimpal', 'Malik, Yashpal Singh', 'Kumar, Satish']",,,,
,PMC,Drug repurposing: a better approach for infectious disease drug discovery?,http://dx.doi.org/10.1016/j.coi.2013.08.004,PMC4015799,,,"The advent of publically available databases containing system-wide phenotypic data of the host response to both drugs and pathogens, in conjunction with bioinformatics and computational methods now allows for in silico predictions of FDA-approved drugs as treatments against infection diseases. This systems biology approach captures the complexity of both the pathogen and drug host response in the form of expression patterns or molecular interaction networks without having to understand the underlying mechanisms of action. These drug repurposing techniques have been successful in identifying new drug candidates for several types of cancers and were recently use to identify potential therapeutics against influenza, the newly discovered Middle Eastern Respiratory Syndrome coronavirus and several parasitic diseases. These new approaches have the potential to significantly reduce both the time and cost for infectious diseases drug discovery.",,"['Law, G. Lynn', 'Tisoncik-Go, Jennifer', 'Korth, Marcus J.', 'Katze, Michael G.']",,,,
,PMC,Inside-out Signaling Promotes Dynamic Changes in the Carcinoembryonic Antigen-related Cellular Adhesion Molecule 1 (CEACAM1) Oligomeric State to Control Its Cell Adhesion Properties,http://dx.doi.org/10.1074/jbc.M113.504639,PMC3795263,,,"Cell-cell contacts are fundamental to multicellular organisms and are subject to exquisite levels of control. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) can engage in both cis-homophilic (parallel) oligomerization and trans-homophilic (anti-parallel) binding. In this study, we establish that the CEACAM1 transmembrane domain has a propensity to form cis-dimers via the transmembrane-embedded (432)GXXXG(436) motif and that this basal state is overcome when activated calmodulin binds to the CEACAM1 cytoplasmic domain. Although mutation of the (432)GXXXG(436) motif reduced CEACAM1 oligomerization, it did not affect surface localization of the receptor or influence CEACAM1-dependent cellular invasion by the pathogenic Neisseria. The mutation did, however, have a striking effect on CEACAM1-dependent cellular aggregation, increasing both the kinetics of cell-cell association and the size of cellular aggregates formed. CEACAM1 association with tyrosine kinase c-Src and tyrosine phosphatases SHP-1 and SHP-2 was not affected by the (432)GXXXG(436) mutation, consistent with their association with the monomeric form of wild type CEACAM1. Collectively, our results establish that a dynamic oligomer-to-monomer shift in surface-expressed CEACAM1 facilitates trans-homophilic binding and downstream effector signaling.",,"['Patel, Prerna C.', 'Lee, Hannah S. W.', 'Ming, Aaron Y. K.', 'Rath, Arianna', 'Deber, Charles M.', 'Yip, Christopher M.', 'Rocheleau, Jonathan V.', 'Gray-Owen, Scott D.']",,,,
,PMC,Novel coronavirus still of international concern,http://dx.doi.org/10.1503/cmaj.109-4552,PMC3761035,,,,,"Brown, Carolyn",,,,
,PMC,Prevalence and analysis of associated risk factors for Cryptosporidium infection in lambs in Jammu district,http://dx.doi.org/10.1007/s12639-013-0353-y,PMC4554585,,,"An epidemiologic study was carried out to investigate the prevalence and analysis of risk of Cryptosporidium infection in lambs in Jammu district. Faecal samples of 120 lambs of different age groups viz., <1 month, 1–3 months and 3–6 months were assessed. Cryptosporidium oocysts were identified by using modified Zeihl Neelsen technique. Statistical analysis showed that infection rates were significantly higher in lambs of <1 month age group (65 %) than other two age groups (p < 0.05). Similarly, cryptosporidial infection rates were significantly higher in diarrhoeic (54.41 %) than in non diarrhoeic lambs (34.61 %). Winter records highest prevalence (73.33 %) which varied significantly. Sex wise higher prevalence was observed in females (51.56 %) as compared to males (39.28 %). The relationship between intensity of infection and various epidemiological factors showed that highest intensity was observed in lambs of 0–1 month age group, having diarrhoea, in winter season.",,"['Ahamed, Irshad', 'Yadav, Anish', 'Katoch, R.', 'Godara, R.', 'Saleem, Taniya', 'Nisar, N. A.']",,,,
,PMC,Cathepsin L Protects Mice from Mycoplasmal Infection and Is Essential for Airway Lymphangiogenesis,http://dx.doi.org/10.1165/rcmb.2013-0016OC,PMC3824055,,,"Cathepsin L (Ctsl) is a proposed therapeutic target to control inflammatory responses in a number of disease states. However, Ctsl is thought to support host defense via its involvement in antigen presentation pathways. Hypothesizing that Ctsl helps combat bacterial infection, we investigated its role in Mycoplasma pulmonis–infected mice as a model of acute and chronic infectious airway inflammation. Responses to the airway inoculation of mycoplasma were compared in Ctsl(−/−) and Ctsl(+/+) mice. After infection, Ctsl(−/−) mice demonstrated more body weight loss, greater mortality (22% versus 0%, respectively), and heavier lungs than Ctsl(+/+) mice, but had smaller bronchial lymph nodes. The burden of live mycoplasma in lungs was 247-fold greater in Ctsl(−/−) mice than in Ctsl(+/+) mice after infection for 3 days. Ctsl(−/−) mice exhibited more severe pneumonia and neutrophil-rich, airway-occlusive exudates, which developed more rapidly than in Ctsl(+/+) mice. Compared with the conspicuous remodeling of lymphatics after infection in Ctsl(+/+) mice, little lymphangiogenesis occurred in Ctsl(−/−) mice, but blood vessel remodeling and tissue inflammation were similarly severe. Titers of mycoplasma-reactive IgM, IgA, and IgG in blood in response to live and heat-killed organisms were similar to those in Ctsl(+/+) mice. However, enzyme-linked immunosorbent spot assays revealed profound reductions in the cellular IFN-γ response to mycoplasma antigen. These findings suggest that Ctsl helps contain mycoplasma infection by supporting lymphangiogenesis and cellular immune responses to infection, and our findings predict that the therapeutic inhibition of Ctsl could increase the severity of mycoplasmal infections.",,"['Xu, Xiang', 'Greenland, John', 'Baluk, Peter', 'Adams, Alicia', 'Bose, Oishee', 'McDonald, Donald M.', 'Caughey, George H.']",,,,
,PMC,The Emerging Role of the Ubiquitin Proteasome in Pulmonary Biology and Disease,http://dx.doi.org/10.1164/rccm.201304-0754PP,PMC3827704,,,"Derangements in normal cellular homeostasis at the protein level can cause or be the consequence of initiation and progression of pulmonary diseases related to genotype, infection, injury, smoking, toxin exposure, or neoplasm. We discuss one of the fundamental mechanisms of protein homeostasis, the ubiquitin proteasome system (UPS), as it relates to lung disease. The UPS effects selective degradation of ubiquitinated target proteins via ubiquitin ligase activity. Important pathobiological mechanisms relating to the UPS and lung disease have been the focus of research, with inappropriate cellular proteolysis now a validated therapeutic target. We review the contributions of this system in various lung diseases, and discuss the exciting area of UPS-targeting drug development for pulmonary disease.",,"['Weathington, Nathaniel M.', 'Sznajder, Jacob I.', 'Mallampalli, Rama K.']",,,,
,PMC,Novel approaches and challenges to treatment of CNS viral infections,http://dx.doi.org/10.1002/ana.23988,PMC4052367,,,"Existing and emerging viral CNS infections are major sources of human morbidity and mortality. Treatments of proven efficacy are currently limited predominantly to herpesviruses and human immunodeficiency virus. Development of new therapies has been hampered by the lack of appropriate animal model systems for some important viruses and by the difficulty in conducting human clinical trials for diseases that may be rare, or in the case of arboviral infections, often have variable seasonal and geographic incidence. Nonetheless, many novel approaches to antiviral therapy are available including candidate thiazolide and purazinecarboxamide derivatives with potential broad-spectrum antiviral efficacy. New herpesvirus drugs include viral helicase-primase and terminase inhibitors. The use of antisense oligonucleotides and other strategies to interfere with viral RNA translation has shown efficacy in experimental models of CNS viral disease. Identifying specific molecular targets within viral replication cycles has led to many existing antivirals and will undoubtedly continue to be the basis of future drug design. A promising new area of research involves therapies based on enhanced understanding of host antiviral immune responses. Toll-like receptor agonists, and drugs that inhibit specific cytokines as well as interferon preparations have all shown potential therapeutic efficacy. Passive transfer of virus-specific cytotoxic T-lymphocytes have been used in humans and may provide an effective therapies for some herpesvirus infections and potentially for progressive multifocal leukoencephalopathy. Humanized monoclonal antibodies directed against specific viral proteins have been developed and in several cases evaluated in humans in settings including West Nile virus and HIV infection and in pre-exposure prophylaxis for rabies.",,"['Nath, Avindra', 'Tyler, Kenneth L.']",,,,
,PMC,Identification of 23-(S)-2-Amino-3-Phenylpropanoyl-Silybin as an Antiviral Agent for Influenza A Virus Infection In Vitro and In Vivo,http://dx.doi.org/10.1128/AAC.00759-13,PMC3754338,,,"It has been reported that autophagy is involved in the replication of many viruses. In this study, we screened 89 medicinal plants, using an assay based on the inhibition of the formation of the Atg12-Atg5/Atg16 heterotrimer, an important regulator of autophagy, and selected Silybum marianum L. for further study. An antiviral assay indicated that silybin (S0), the major active compound of S. marianum L., can inhibit influenza A virus (IAV) infection. We later synthesized 5 silybin derivatives (S1 through S5) and found that 23-(S)-2-amino-3-phenylpropanoyl-silybin (S3) had the best activity. When we compared the polarities of the substituent groups, we found that the hydrophobicity of the substituent groups was positively correlated with their activities. We further studied the mechanisms of action of these compounds and determined that S0 and S3 also inhibited both the formation of the Atg12-Atg5/Atg16 heterotrimer and the elevated autophagy induced by IAV infection. In addition, we found that S0 and S3 could inhibit several components induced by IAV infection, including oxidative stress, the activation of extracellular signal-regulated kinase (ERK)/p38 mitogen-activated protein kinase (MAPK) and IκB kinase (IKK) pathways, and the expression of autophagic genes, especially Atg7 and Atg3. All of these components have been reported to be related to the formation of the Atg12-Atg5/Atg16 heterotrimer, which might validate our screening strategy. Finally, we demonstrated that S3 can significantly reduce influenza virus replication and the associated mortality in infected mice. In conclusion, we identified 23-(S)-2-amino-3-phenylpropanoyl-silybin as a promising inhibitor of IAV infection.",,"['Dai, Jian-Ping', 'Wu, Li-Qi', 'Li, Rui', 'Zhao, Xiang-Feng', 'Wan, Qian-Ying', 'Chen, Xiao-Xuan', 'Li, Wei-Zhong', 'Wang, Ge-Fei', 'Li, Kang-Sheng']",,,,
,PMC,Communications in Public Health Emergency Preparedness: A Systematic Review of the Literature,http://dx.doi.org/10.1089/bsp.2013.0038,PMC3778998,,,"During a public health crisis, public health agencies engage in a variety of public communication efforts to inform the population, encourage the adoption of preventive behaviors, and limit the impact of adverse events. Given the importance of communication to the public in public health emergency preparedness, it is critical to examine the extent to which this field of study has received attention from the scientific community. We conducted a systematic literature review to describe current research in the area of communication to the public in public health emergency preparedness, focusing on the association between sociodemographic and behavioral factors and communication as well as preparedness outcomes. Articles were searched in PubMed and Embase and reviewed by 2 independent reviewers. A total of 131 articles were included for final review. Fifty-three percent of the articles were empirical, of which 74% were population-based studies, and 26% used information environment analysis techniques. None had an experimental study design. Population-based studies were rarely supported by theoretical models and mostly relied on a cross-sectional study design. Consistent results were reported on the association between population socioeconomic factors and public health emergency preparedness communication and preparedness outcomes. Our findings show the need for empirical research to determine what type of communication messages can be effective in achieving preparedness outcomes across various population groups. They suggest that a real-time analysis of the information environment is valuable in knowing what is being communicated to the public and could be used for course correction of public health messages during a crisis.",,"['Savoia, Elena', 'Lin, Leesa', 'Viswanath, Kasisomayajula']",,,,
,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.13.010913,PMC3790218,,,,,,,,,
,PMC,Public Health Watch,http://dx.doi.org/10.1177/1715163513502152,PMC3785204,,,,,"Lynas, Kathie",,,,
,PMC,"Clinical, hematological, and biochemical findings in puppies with coronavirus and parvovirus enteritis",,PMC3743577,,,"The clinical and laboratory findings in puppies naturally infected with canine coronavirus (CCoV) and/or canine parvovirus (CPV) were compared with findings in uninfected puppies. Lymphopenia was the only parameter related to CCoV infection that was statistically significant; vomiting, anorexia, lethargy, hemorrhagic fluid diarrhea, leukopenia, lymphopenia, thrombocytopenia, hypoglycemia, and hypoproteinemia were correlated with CPV infection.",,"['Castro, Tatiana X.', 'Cubel Garcia, Rita de Cássia N.', 'Gonçalves, Luciana P. S.', 'Costa, Erika M.', 'Marcello, Gracy C.G.', 'Labarthe, Norma V.', 'Mendes-de-Almeida, Flavya']",,,,
,PMC,"Virulence, Transmission, and Heterologous Protection of Four Isolates of Haemophilus parasuis",http://dx.doi.org/10.1128/CVI.00168-13,PMC3889593,,,"Haemophilus parasuis causes Glässer's disease, a syndrome of polyserositis, meningitis, and arthritis in swine. Previous studies with H. parasuis have revealed virulence disparity among isolates and inconsistent heterologous protection. In this study, virulence, direct transmission, and heterologous protection of 4 isolates of H. parasuis (SW114, 12939, MN-H, and 29755) were evaluated using a highly susceptible pig model. In an initial experiment, isolates 12939, MN-H, and 29755 caused Glässer's disease, while strain SW114 failed to cause any clinical signs of disease. One pig from each group challenged with MN-H or 29755 failed to develop clinical disease but was able to transmit H. parasuis to noninfected pigs, which subsequently developed Glässer's disease. Pigs colonized with SW114, 29755, or MN-H that were free of clinical disease were protected from a subsequent challenge with isolate 12939. In a following experiment, pigs vaccinated with strain SW114 given as either a bacterin intramuscularly or a live intranasal vaccine were protected from subsequent challenge with isolate 12939; however, some pigs given live SW114 developed arthritis. Overall these studies demonstrated that pigs infected with virulent isolates of H. parasuis can remain healthy and serve as reservoirs for transmission to naive pigs and that heterologous protection among H. parasuis isolates is possible. In addition, further attenuation of strain SW114 is necessary if it is to be used as a live vaccine.",,"['Brockmeier, Susan L.', 'Loving, Crystal L.', 'Mullins, Michael A.', 'Register, Karen B.', 'Nicholson, Tracy L.', 'Wiseman, Barry S.', 'Baker, Rodney B.', 'Kehrli, Marcus E.']",,,,
,PMC,"Human Antibody Neutralizes Severe Fever with Thrombocytopenia Syndrome Virus, an Emerging Hemorrhagic Fever Virus",http://dx.doi.org/10.1128/CVI.00222-13,PMC3889583,,,"Severe fever with thrombocytopenia syndrome virus (SFTSV), a newly discovered member of the Bunyaviridae family, is the causative agent of an emerging hemorrhagic fever, SFTS, in China. Currently, there are no vaccines or effective therapies against SFTS. In this study, a combinatorial human antibody library was constructed from the peripheral lymphocytes of 5 patients who had recovered from SFTS. The library was screened against purified virions for the production of single-chain variable-region fragments (ScFv). Of the 6 positive clones, one clone (monoclonal antibody [MAb] 4-5) showed neutralizing activity against SFTSV infection in Vero cells. MAb 4-5 was found to effectively neutralize all of the clinical isolates of SFTSV tested, which were isolated from patients in China from 2010 to 2012. MAb 4-5 was found to bind a linear epitope in the ectodomain of glycoprotein Gn. Its neutralizing activity is attributed to blockage of the interactions between the Gn protein and the cellular receptor, indicating that inhibition of virus-cell attachment is its main mechanism. These data suggest that MAb 4-5 can be used as a promising candidate molecule for immunotherapy against SFTSV infection.",,"['Guo, Xiling', 'Zhang, Li', 'Zhang, Wenshuai', 'Chi, Ying', 'Zeng, Xiaoyan', 'Li, Xian', 'Qi, Xian', 'Jin, Qiu', 'Zhang, Xiao', 'Huang, Mingming', 'Wang, Hua', 'Chen, Yin', 'Bao, Changjun', 'Hu, Jianli', 'Liang, Shuyi', 'Bao, Lin', 'Wu, Tao', 'Zhou, Minghao', 'Jiao, Yongjun']",,,,
,PMC,Correlation Between Mutation Rate and Genome Size in Riboviruses: Mutation Rate of Bacteriophage Qβ,http://dx.doi.org/10.1534/genetics.113.154963,PMC3761305,,,"Genome sizes and mutation rates covary across all domains of life. In unicellular organisms and DNA viruses, they show an inverse relationship known as Drake’s rule. However, it is still unclear whether a similar relationship exists between genome sizes and mutation rates in RNA genomes. Coronaviruses, the RNA viruses with the largest genomes (∼30 kb), encode a proofreading 3′ exonuclease that allows them to increase replication fidelity. However, it is unknown whether, conversely, the RNA viruses with the smallest genomes tend to show particularly high mutation rates. To test this, we measured the mutation rate of bacteriophage Qβ, a 4.2-kb levivirus. Amber reversion-based Luria–Delbrück fluctuation tests combined with mutant sequencing gave an estimate of 1.4 × 10(−4) substitutions per nucleotide per round of copying, the highest mutation rate reported for any virus using this method. This estimate was confirmed using a direct plaque sequencing approach and after reanalysis of previously published estimates for this phage. Comparison with other riboviruses (all RNA viruses except retroviruses) provided statistical support for a negative correlation between mutation rates and genome sizes. We suggest that the mutation rates of RNA viruses might be optimized for maximal adaptability and that the value of this optimum may in turn depend inversely on genome size.",,"['Bradwell, Katie', 'Combe, Marine', 'Domingo-Calap, Pilar', 'Sanjuán, Rafael']",,,,
,PMC,"Virus infection, antiviral immunity, and autoimmunity",http://dx.doi.org/10.1111/imr.12091,PMC3971377,,,"As a group of disorders, autoimmunity ranks as the third most prevalent cause of morbidity and mortality in the Western World. However, the etiology of most autoimmune diseases remains unknown. Although genetic linkage studies support a critical underlying role for genetics, the geographic distribution of these disorders as well as the low concordance rates in monozygotic twins suggest that a combination of other factors including environmental ones are involved. Virus infection is a primary factor that has been implicated in the initiation of autoimmune disease. Infection triggers a robust and usually well-coordinated immune response that is critical for viral clearance. However, in some instances, immune regulatory mechanisms may falter, culminating in the breakdown of self-tolerance, resulting in immune-mediated attack directed against both viral and self-antigens. Traditionally, cross-reactive T-cell recognition, known as molecular mimicry, as well as bystander T-cell activation, culminating in epitope spreading, have been the predominant mechanisms elucidated through which infection may culminate in an T-cell-mediated autoimmune response. However, other hypotheses including virus-induced decoy of the immune system also warrant discussion in regard to their potential for triggering autoimmunity. In this review, we discuss the mechanisms by which virus infection and antiviral immunity contribute to the development of autoimmunity.",,"['Getts, Daniel R.', 'Chastain, Emily M. L.', 'Terry, Rachael L.', 'Miller, Stephen D.']",,,,
,PMC,Immunity to viruses,http://dx.doi.org/10.1111/imr.12109,PMC3810961,,,,,"['Braciale, Thomas J.', 'Hahn, Young S.']",,,,
,PMC,Bugs in the System,http://dx.doi.org/10.1111/imr.12092,PMC3748621,,,"Immunity to respiratory virus infection is governed by complex biological networks that influence disease progression and pathogenesis. Systems biology provides an opportunity to explore and understand these multifaceted interactions based on integration and modeling of multiple biological parameters. In this review, we describe new and refined systems-based approaches used to model, identify, and validate novel targets within complex networks following influenza and coronavirus infection. In addition, we propose avenues for extension and expansion that can revolutionize our understanding of infectious disease processes. Together, we hope to provide a window into the unique and expansive opportunity presented by systems biology to understand complex disease processes within the context of infectious diseases.",,"['Menachery, Vineet D.', 'Baric, Ralph S.']",,,,
,PMC,The great balancing act: regulation and fate of antiviral T-cell interactions,http://dx.doi.org/10.1111/imr.12093,PMC3748617,,,"The fate of T lymphocytes revolves around a continuous stream of interactions between the T-cell receptor (TCR) and peptide-major histocompatibility complex (MHC) molecules. Beginning in the thymus and continuing into the periphery, these interactions, refined by accessory molecules, direct the expansion, differentiation, and function of T-cell subsets. The cellular context of T-cell engagement with antigen-presenting cells, either in lymphoid or nonlymphoid tissues, plays an important role in determining how these cells respond to antigen encounters. CD8(+) T cells are essential for clearance of a lymphocytic choriomeningitis virus (LCMV) infection, but the virus can present a number of unique challenges that antiviral T cells must overcome. Peripheral LCMV infection can lead to rapid cytolytic clearance or chronic viral persistence; central nervous system infection can result in T-cell-dependent fatal meningitis or an asymptomatic carrier state amenable to immunotherapeutic clearance. These diverse outcomes all depend upon interactions that require TCR engagement of cognate peptide-MHC complexes. In this review, we explore the diversity in antiviral T-cell behaviors resulting from TCR engagement, beginning with an overview of the immunological synapse and progressing to regulators of TCR signaling that shape the delicate balance between immunopathology and viral clearance.",,"['Moseman, E. Ashley', 'McGavern, Dorian B.']",,,,
,PMC,H1N1 influenza pandemic: What we did and what we learnt?,http://dx.doi.org/10.4103/0972-5229.120316,PMC3841487,24339636,CC BY-NC-SA,,2013 Sep-Oct,"['Jog, Sameer', 'Kadam, Deelip']",Indian J Crit Care Med,,,
,PMC,"Comparison of the FilmArray RP, Verigene RV+, and Prodesse ProFLU+/FAST+ Multiplex Platforms for Detection of Influenza Viruses in Clinical Samples from the 2011-2012 Influenza Season in Belgium",http://dx.doi.org/10.1128/JCM.00911-13,PMC3754662,,,"Respiratory tract infections (RTIs) are caused by a plethora of viral and bacterial pathogens. In particular, lower RTIs are a leading cause of hospitalization and mortality. Timely detection of the infecting respiratory pathogens is crucial to optimize treatment and care. In this study, three U.S. Food and Drug Administration-approved molecular multiplex platforms (Prodesse ProFLU+/FAST+, FilmArray RP, and Verigene RV+) were evaluated for influenza virus detection in 171 clinical samples collected during the Belgian 2011-2012 influenza season. Sampling was done using mid-turbinate flocked swabs, and the collected samples were stored in universal transport medium. The amount of viral RNA present in the swab samples ranged between 3.07 and 8.82 log(10) copies/ml. Sixty samples were concordant influenza A virus positive, and 8 samples were found to be concordant influenza B virus positive. Other respiratory viruses that were detected included human rhinovirus/enterovirus, respiratory syncytial virus, parainfluenza virus type 1, human metapneumovirus, and coronavirus NL63. Twenty-five samples yielded discordant results across the various assays which required further characterization by sequencing. The FilmArray RP and Prodesse ProFLU+/FAST+ assays were convenient to perform with regard to sensitivity, ease of use, and low percentages of invalid results. Although the limit of sensitivity is of utmost importance, many other factors should be taken into account in selecting the most convenient molecular diagnostic assay for the detection of respiratory pathogens in clinical samples.",,"['Van Wesenbeeck, Liesbeth', 'Meeuws, Hanne', 'Van Immerseel, Andrea', 'Ispas, Gabriela', 'Schmidt, Kristiane', 'Houspie, Lieselot', 'Van Ranst, Marc', 'Stuyver, Lieven']",,,,
,PMC,High Incidence but Low Burden of Coronaviruses and Preferential Associations between Respiratory Viruses,http://dx.doi.org/10.1128/JCM.01078-13,PMC3754627,,,"Respiratory viruses are the leading cause of acute infections in humans. However, the burden of certain respiratory viruses, such as coronaviruses, and the relevance of viral coinfections remain unclear. In this study, we investigated the distribution and seasonal occurrences of respiratory viruses detected by multiplex molecular assay in 6,014 samples from 2008 to 2011 in a French hospital. We assessed the detection frequencies of 14 respiratory viruses and their clinical impact in immunosuppressed and nonimmunosuppressed patients. Furthermore, we explored the preferential association patterns between respiratory viruses in multiple infections. Our results indicated that human rhinovirus/enterovirus (HRV/EV) and coronavirus (HCoV) were frequently detected in respiratory samples (48.81% and 11.74% of infected samples, respectively), and the detection frequencies of these viruses were further increased in immunosuppressed patients. The most common subtypes of HCoV were HCoV-229E (33.80%) and HCoV-HKU1 (32.39%). A sharp increase in the detection frequencies of HCoV-229E and HCoV-HKU1 over several months suggested that these subtypes were epidemic in our population. In immunosuppressed patients, HCoV contributed to upper respiratory tract infections (52%). Evidence did not support lower respiratory tract infections exclusive to a unique HCoV infection. In multiply infected individuals, determined in 6.3% of samples, HRV/EV and HCoV were detected in 33.29% and 22.90% of samples, respectively. Interestingly, nearly 50% of HCoV infections were detected in association with another virus. Since the distributions of respiratory viruses in multiply infected patients were subject to preferential association patterns between viruses, we propose complex interactions between different respiratory viruses and host factors.",,"['Lepiller, Q.', 'Barth, H.', 'Lefebvre, F.', 'Herbrecht, R.', 'Lutz, P.', 'Kessler, R.', 'Fafi-Kremer, S.', 'Stoll-Keller, F.']",,,,
,PMC,Median infectious dose of human norovirus GII.4 in gnotobiotic pigs is decreased by simvastatin treatment and increased by age,http://dx.doi.org/10.1099/vir.0.054080-0,PMC3749057,,,"Human noroviruses (NoVs), a major cause of viral gastroenteritis, are difficult to study due to the lack of a cell-culture and a small-animal model. Pigs share with humans the types A and H histo-blood group antigens on the intestinal epithelium and have been suggested as a potential model for studies of NoV pathogenesis, immunity and vaccines. In this study, the effects of age and a cholesterol-lowering drug, simvastatin, on the susceptibility of pigs to NoV infection were evaluated. The median infectious dose (ID(50)) of a genogroup II, genotype 4 (GII.4) 2006b variant was determined. The ID(50) in neonatal (4–5 days of age) pigs was ≤2.74×10(3) viral RNA copies. In older pigs (33–34 days of age), the ID(50) was 6.43×10(4) but decreased to <2.74×10(3) in simvastatin-fed older pigs. Evidence of NoV infection was obtained by increased virus load in the intestinal contents, cytopathological changes in the small intestine, including irregular microvilli, necrosis and apoptosis, and detection of viral antigen in the tip of villi in duodenum. This GII.4 variant was isolated in 2008 from a patient from whom a large volume of stool was collected. GII.4 NoVs are continuously subjected to selective pressure by human immunity, and antigenically different GII.4 NoV variants emerge every 1–2 years. The determination of the ID(50) of this challenge virus is valuable for evaluation of protection against different GII.4 variants conferred by NoV vaccines in concurrence with other GII.4 variants in the gnotobiotic pig model.",,"['Bui, Tammy', 'Kocher, Jacob', 'Li, Yanru', 'Wen, Ke', 'Li, Guohua', 'Liu, Fangning', 'Yang, Xingdong', 'LeRoith, Tanya', 'Tan, Ming', 'Xia, Ming', 'Zhong, Weiming', 'Jiang, Xi', 'Yuan, Lijuan']",,,,
,PMC,Recent host-shifts in ranaviruses: signatures of positive selection in the viral genome,http://dx.doi.org/10.1099/vir.0.052837-0,PMC3749056,,,"Ranaviruses have been implicated in recent declines in global amphibian populations. Compared with the family Iridoviridae, to which the genus Ranavirus belongs, ranaviruses have a wide host range in that species/strains are known to infect fish, amphibians and reptiles, presumably due to recent host-switching events. We used eight sequenced ranavirus genomes and two selection-detection methods (site based and branch based) to identify genes that exhibited signatures of positive selection, potentially due to the selective pressures at play during host switching. We found evidence of positive selection acting on four genes via the site-based method, three of which were newly acquired genes unique to ranavirus genomes. Using the branch-based method, we identified eight additional candidate genes that exhibited signatures of d(N)/d(S) (non-synonymous/synonymous substitution rate) >1 in the clade where intense host switching had occurred. We found that these branch-specific patterns of elevated d(N)/d(S) were enriched in a small group of viral genes that have been acquired most recently in the ranavirus genome, compared with core genes that are shared among all members of the family Iridoviridae. Our results suggest that the group of newly acquired genes in the ranavirus genome may have undergone recent adaptive changes that have facilitated interspecies and interclass host switching.",,"['Abrams, A. Jeanine', 'Cannatella, David C.', 'Hillis, David M.', 'Sawyer, Sara L.']",,,,
,PMC,Development of Norwalk Virus-Specific Monoclonal Antibodies with Therapeutic Potential for the Treatment of Norwalk Virus Gastroenteritis,http://dx.doi.org/10.1128/JVI.01376-13,PMC3754140,,,"Passive immunoprophylaxis or immunotherapy with norovirus-neutralizing monoclonal antibodies (MAbs) could be a useful treatment for high-risk populations, including infants and young children, the elderly, and certain patients who are debilitated or immunocompromised. In order to obtain antinorovirus MAbs with therapeutic potential, we stimulated a strong adaptive immune response in chimpanzees to the prototype norovirus strain Norwalk virus (NV) (genogroup I.1). A combinatorial phage Fab display library derived from mRNA of the chimpanzees' bone marrow was prepared, and four distinct Fabs reactive with Norwalk recombinant virus-like particles (rVLPs) were recovered, with estimated binding affinities in the subnanomolar range. Mapping studies showed that the four Fabs recognized three different conformational epitopes in the protruding (P) domain of NV VP1, the major capsid protein. The epitope of one of the Fabs, G4, was further mapped to a specific site involving a key amino acid residue, Gly365. One additional specific Fab (F11) was recovered months later from immortalized memory B cells and partially characterized. The anti-NV Fabs were converted into full-length IgG (MAbs) with human γ1 heavy chain constant regions. The anti-NV MAbs were tested in the two available surrogate assays for Norwalk virus neutralization, which showed that the MAbs could block carbohydrate binding and inhibit hemagglutination by NV rVLP. By mixing a single MAb with live Norwalk virus prior to challenge, MAbs D8 and B7 neutralized the virus and prevented infection in a chimpanzee. Because chimpanzee immunoglobulins are virtually identical to human immunoglobulins, these chimpanzee anticapsid MAbs may have a clinical application.",,"['Chen, Zhaochun', 'Sosnovtsev, Stanislav V.', 'Bok, Karin', 'Parra, Gabriel I.', 'Makiya, Michelle', 'Agulto, Liane', 'Green, Kim Y.', 'Purcell, Robert H.']",,,,
,PMC,Bilateral Entry and Release of Middle East Respiratory Syndrome Coronavirus Induces Profound Apoptosis of Human Bronchial Epithelial Cells,http://dx.doi.org/10.1128/JVI.01562-13,PMC3754134,,,"The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) infects human bronchial epithelial Calu-3 cells. Unlike severe acute respiratory syndrome (SARS)-CoV, which exclusively infects and releases through the apical route, this virus can do so through either side of polarized Calu-3 cells. Infection results in profound apoptosis within 24 h irrespective of its production of titers that are lower than those of SARS-CoV. Together, our results provide new insights into the dissemination and pathogenesis of MERS-CoV and may indicate that the virus differs markedly from SARS-CoV.",,"['Tao, Xinrong', 'Hill, Terence E.', 'Morimoto, Chikao', 'Peters, Clarence J.', 'Ksiazek, Thomas G.', 'Tseng, Chien-Te K.']",,,,
,PMC,Identification of a Receptor-Binding Domain in the S Protein of the Novel Human Coronavirus Middle East Respiratory Syndrome Coronavirus as an Essential Target for Vaccine Development,http://dx.doi.org/10.1128/JVI.01048-13,PMC3754113,,,"A novel human Middle East respiratory syndrome coronavirus (MERS-CoV) caused outbreaks of severe acute respiratory syndrome (SARS)-like illness with a high mortality rate, raising concerns of its pandemic potential. Dipeptidyl peptidase-4 (DPP4) was recently identified as its receptor. Here we showed that residues 377 to 662 in the S protein of MERS-CoV specifically bound to DPP4-expressing cells and soluble DPP4 protein and induced significant neutralizing antibody responses, suggesting that this region contains the receptor-binding domain (RBD), which has a potential to be developed as a MERS-CoV vaccine.",,"['Du, Lanying', 'Zhao, Guangyu', 'Kou, Zhihua', 'Ma, Cuiqing', 'Sun, Shihui', 'Poon, Vincent K. M.', 'Lu, Lu', 'Wang, Lili', 'Debnath, Asim K.', 'Zheng, Bo-Jian', 'Zhou, Yusen', 'Jiang, Shibo']",,,,
,PMC,Herpes Simplex Virus 1-Encoded Tegument Protein VP16 Abrogates the Production of Beta Interferon (IFN) by Inhibiting NF-κB Activation and Blocking IFN Regulatory Factor 3 To Recruit Its Coactivator CBP,http://dx.doi.org/10.1128/JVI.01440-13,PMC3754106,,,"Host cells activate innate immune signaling pathways to defend against invading pathogens. To survive within an infected host, viruses have evolved intricate strategies to counteract host immune responses. Herpesviruses, including herpes simplex virus type 1 (HSV-1), have large genomes and therefore have the capacity to encode numerous proteins that modulate host innate immune responses. Here we define the contribution of HSV-1 tegument protein VP16 in the inhibition of beta interferon (IFN-β) production. VP16 was demonstrated to significantly inhibit Sendai virus (SeV)-induced IFN-β production, and its transcriptional activation domain was not responsible for this inhibition activity. Additionally, VP16 blocked the activation of the NF-κB promoter induced by SeV or tumor necrosis factor alpha treatment and expression of NF-κB-dependent genes through interaction with p65. Coexpression analysis revealed that VP16 selectively blocked IFN regulatory factor 3 (IRF-3)-mediated but not IRF-7-mediated transactivation. VP16 was able to bind to IRF-3 but not IRF-7 in vivo, based on coimmunoprecipitation analysis, but it did not affect IRF-3 dimerization, nuclear translocation, or DNA binding activity. Rather, VP16 interacted with the CREB binding protein (CBP) coactivator and efficiently inhibited the formation of the transcriptional complexes IRF-3–CBP in the context of HSV-1 infection. These results illustrate that VP16 is able to block the production of IFN-β by inhibiting NF-κB activation and interfering with IRF-3 to recruit its coactivator CBP, which may be important to the early events leading to HSV-1 infection.",,"['Xing, Junji', 'Ni, Liwen', 'Wang, Shuai', 'Wang, Kezhen', 'Lin, Rongtuan', 'Zheng, Chunfu']",,,,
,PMC,Increased Acid Stability of the Hemagglutinin Protein Enhances H5N1 Influenza Virus Growth in the Upper Respiratory Tract but Is Insufficient for Transmission in Ferrets,http://dx.doi.org/10.1128/JVI.01175-13,PMC3754100,,,"Influenza virus entry is mediated by the acidic-pH-induced activation of hemagglutinin (HA) protein. Here, we investigated how a decrease in the HA activation pH (an increase in acid stability) influences the properties of highly pathogenic H5N1 influenza virus in mammalian hosts. We generated isogenic A/Vietnam/1203/2004 (H5N1) (VN1203) viruses containing either wild-type HA protein (activation pH 6.0) or an HA2-K58I point mutation (K to I at position 58) (activation pH 5.5). The VN1203-HA2-K58I virus had replication kinetics similar to those of wild-type VN1203 in MDCK and normal human bronchial epithelial cells and yet had reduced growth in human alveolar A549 cells, which were found to have a higher endosomal pH than MDCK cells. Wild-type and HA2-K58I viruses promoted similar levels of morbidity and mortality in C57BL/6J mice and ferrets, and neither virus transmitted efficiently to naive contact cage-mate ferrets. The acid-stabilizing HA2-K58I mutation, which diminishes H5N1 replication and transmission in ducks, increased the virus load in the ferret nasal cavity early during infection while simultaneously reducing the virus load in the lungs. Overall, a single, acid-stabilizing mutation was found to enhance the growth of an H5N1 influenza virus in the mammalian upper respiratory tract, and yet it was insufficient to enable contact transmission in ferrets in the absence of additional mutations that confer α(2,6) receptor binding specificity and remove a critical N-linked glycosylation site. The information provided here on the contribution of HA acid stability to H5N1 influenza virus fitness and transmissibility in mammals in the background of a non-laboratory-adapted virus provides essential information for the surveillance and assessment of the pandemic potential of currently circulating H5N1 viruses.",,"['Zaraket, Hassan', 'Bridges, Olga A.', 'Duan, Susu', 'Baranovich, Tatiana', 'Yoon, Sun-Woo', 'Reed, Mark L.', 'Salomon, Rachelle', 'Webby, Richard J.', 'Webster, Robert G.', 'Russell, Charles J.']",,,,
,PMC,Alphacoronavirus Protein 7 Modulates Host Innate Immune Response,http://dx.doi.org/10.1128/JVI.01032-13,PMC3754097,,,"Innate immune response is the first line of antiviral defense resulting, in most cases, in pathogen clearance with minimal clinical consequences. Viruses have developed diverse strategies to subvert host defense mechanisms and increase their survival. In the transmissible gastroenteritis virus (TGEV) as a model, we previously reported that accessory gene 7 counteracts the host antiviral response by associating with the catalytic subunit of protein phosphatase 1 (PP1c). In the present work, the effect of the absence of gene 7 on the host cell, during infection, was further analyzed by transcriptomic analysis. The pattern of gene expression of cells infected with a recombinant mutant TGEV, lacking gene 7 expression (rTGEV-Δ7), was compared to that of cells infected with the parental virus (rTGEV-wt). Genes involved in the immune response, the interferon response, and inflammation were upregulated during TGEV infection in the absence of gene 7. An exacerbated innate immune response during infection with rTGEV-Δ7 virus was observed both in vitro and in vivo. An increase in macrophage recruitment and activation in lung tissues infected with rTGEV-Δ7 virus was observed compared to cells infected with the parental virus. In summary, the absence of protein 7 both in vitro and in vivo led to increased proinflammatory responses and acute tissue damage after infection. In a porcine animal model, which is immunologically similar to humans, we present a novel example of how viral proteins counteract host antiviral pathways to determine the infection outcome and pathogenesis.",,"['Cruz, Jazmina L. G.', 'Becares, Martina', 'Sola, Isabel', 'Oliveros, Juan Carlos', 'Enjuanes, Luis', 'Zúñiga, Sonia']",,,,
,PMC,The Cellular Interactome of the Coronavirus Infectious Bronchitis Virus Nucleocapsid Protein and Functional Implications for Virus Biology,http://dx.doi.org/10.1128/JVI.00321-13,PMC3754094,,,"The coronavirus nucleocapsid (N) protein plays a multifunctional role in the virus life cycle, from regulation of replication and transcription and genome packaging to modulation of host cell processes. These functions are likely to be facilitated by interactions with host cell proteins. The potential interactome of the infectious bronchitis virus (IBV) N protein was mapped using stable isotope labeling with amino acids in cell culture (SILAC) coupled to a green fluorescent protein-nanotrap pulldown methodology and liquid chromatography-tandem mass spectrometry. The addition of the SILAC label allowed discrimination of proteins that were likely to specifically bind to the N protein over background binding. Overall, 142 cellular proteins were selected as potentially binding to the N protein, many as part of larger possible complexes. These included ribosomal proteins, nucleolar proteins, translation initiation factors, helicases, and hnRNPs. The association of selected cellular proteins with IBV N protein was confirmed by immunoblotting, cosedimentation, and confocal microscopy. Further, the localization of selected proteins in IBV-infected cells as well as their activity during virus infection was assessed by small interfering RNA-mediated depletion, demonstrating the functional importance of cellular proteins in the biology of IBV. This interactome not only confirms previous observations made with other coronavirus and IBV N proteins with both overexpressed proteins and infectious virus but also provides novel data that can be exploited to understand the interaction between the virus and the host cell.",,"['Emmott, Edward', 'Munday, Diane', 'Bickerton, Erica', 'Britton, Paul', 'Rodgers, Mark A.', 'Whitehouse, Adrian', 'Zhou, En-Min', 'Hiscox, Julian A.']",,,,
,PMC,Palmitoylation on Conserved and Nonconserved Cysteines of Murine IFITM1 Regulates Its Stability and Anti-Influenza A Virus Activity,http://dx.doi.org/10.1128/JVI.00621-13,PMC3754091,,,"The interferon-induced transmembrane proteins (IFITMs) restrict infection by numerous viruses, yet the importance and regulation of individual isoforms remains unclear. Here, we report that murine IFITM1 (mIFITM1) is palmitoylated on one nonconserved cysteine and three conserved cysteines that are required for anti-influenza A virus activity. Additionally, palmitoylation of mIFITM1 regulates protein stability by preventing proteasomal degradation, and modification of the nonconserved cysteine at the mIFITM1 C terminus supports an intramembrane topology with mechanistic implications.",,"['Hach, Jocelyn C.', 'McMichael, Temet', 'Chesarino, Nicholas M.', 'Yount, Jacob S.']",,,,
,PMC,Characterization of the Bas-Congo Virus Glycoprotein and Its Function in Pseudotyped Viruses,http://dx.doi.org/10.1128/JVI.01183-13,PMC3754090,,,"Bas-Congo virus (BASV) is a novel rhabdovirus recently identified from a patient with acute hemorrhagic fever in the Bas-Congo province of the Democratic Republic of Congo (DRC). Here we show that the BASV glycoprotein (BASV-G) can be successfully used to pseudotype glycoprotein-deficient vesicular stomatitis virus (VSV), allowing studies of BASV-G-driven membrane fusion and viral entry into target cells without replication-competent virus. BASV-G displayed broad tissue and species tropism in vitro, and BASV-G-mediated membrane fusion was pH dependent. The conformational changes induced in BASV-G by acidification were fully reversible and did not lead to inactivation of the viral fusion protein. Our data combined with comparative sequence similarity analyses suggest that BASV-G shares structural and functional features with other rhabdovirus glycoproteins and falls into the group of class III viral fusion proteins. However, activation of BASV-G-driven fusion required a lower pH and higher temperatures than did VSV-G-mediated fusion. Moreover, in contrast to VSV-G, mature BASV-G in VSV pseudotypes consists of a mixture of high-mannose and complex glycans that enables it to bind to certain C-type lectins, thereby enhancing its attachment to target cells. Taken together, the results presented in this study will facilitate future investigations of BASV-G-mediated cell entry and its inhibition in the absence of an infectious cell culture assay for BASV and at lower biosafety levels. Moreover, serology testing based on BASV-G pseudotype neutralization can be used to uncover the prevalence and importance of BASV as a potential novel human pathogen in the DRC and throughout Central Africa.",,"['Steffen, Imke', 'Liss, Nathan M.', 'Schneider, Bradley S.', 'Fair, Joseph N.', 'Chiu, Charles Y.', 'Simmons, Graham']",,,,
,PMC,A Novel Rabbit Monoclonal Antibody Platform To Dissect the Diverse Repertoire of Antibody Epitopes for HIV-1 Env Immunogen Design,http://dx.doi.org/10.1128/JVI.00837-13,PMC3754024,,,"The majority of available monoclonal antibodies (MAbs) in the current HIV vaccine field are generated from HIV-1-infected people. In contrast, preclinical immunogenicity studies have mainly focused on polyclonal antibody responses in experimental animals. Although rabbits have been widely used for antibody studies, there has been no report of using rabbit MAbs to dissect the specificity of antibody responses for AIDS vaccine development. Here we report on the production of a panel of 12 MAbs from a New Zealand White (NZW) rabbit that was immunized with an HIV-1 JR-FL gp120 DNA prime and protein boost vaccination regimen. These rabbit MAbs recognized a diverse repertoire of envelope (Env) epitopes ranging from the highly immunogenic V3 region to several previously underappreciated epitopes in the C1, C4, and C5 regions. Nine MAbs showed cross-reactivity to gp120s of clades other than clade B. Increased somatic mutation and extended CDR3 were observed with Ig genes of several molecularly cloned rabbit MAbs. Phylogenic tree analysis showed that the heavy chains of MAbs recognizing the same region on gp120 tend to segregate into an independent subtree. At least three rabbit MAbs showed neutralizing activities with various degrees of breadth and potency. The establishment of this rabbit MAb platform will significantly enhance our ability to test optimal designs of Env immunogens to gain a better understanding of the structural specificity and evolution process of Env-specific antibody responses elicited by candidate AIDS vaccines.",,"['Chen, Yuxin', 'Vaine, Michael', 'Wallace, Aaron', 'Han, Dong', 'Wan, Shengqin', 'Seaman, Michael S.', 'Montefiori, David', 'Wang, Shixia', 'Lu, Shan']",,,,
,PMC,Ifit1 Inhibits Japanese Encephalitis Virus Replication through Binding to 5′ Capped 2′-O Unmethylated RNA,http://dx.doi.org/10.1128/JVI.00883-13,PMC3754022,,,"The interferon-inducible protein with tetratricopeptide (IFIT) family proteins inhibit replication of some viruses by recognizing several types of RNAs, including 5′-triphosphate RNA and 5′ capped 2′-O unmethylated mRNA. However, it remains unclear how IFITs inhibit replication of some viruses through recognition of RNA. Here, we analyzed the mechanisms by which Ifit1 exerts antiviral responses. Replication of a Japanese encephalitis virus (JEV) 2′-O methyltransferase (MTase) mutant was markedly enhanced in mouse embryonic fibroblasts and macrophages lacking Ifit1. Ifit1 bound 5′-triphosphate RNA but more preferentially associated with 5′ capped 2′-O unmethylated mRNA. Ifit1 inhibited the translation of mRNA and thereby restricted the replication of JEV mutated in 2′-O MTase. Thus, Ifit1 inhibits replication of MTase-defective JEV by inhibiting mRNA translation through direct binding to mRNA 5′ structures.",,"['Kimura, Taishi', 'Katoh, Hiroshi', 'Kayama, Hisako', 'Saiga, Hiroyuki', 'Okuyama, Megumi', 'Okamoto, Toru', 'Umemoto, Eiji', 'Matsuura, Yoshiharu', 'Yamamoto, Masahiro', 'Takeda, Kiyoshi']",,,,
,PMC,Magnetic Fractionation and Proteomic Dissection of Cellular Organelles Occupied by the Late Replication Complexes of Semliki Forest Virus,http://dx.doi.org/10.1128/JVI.01105-13,PMC3754020,,,"Alphavirus replicase complexes are initially formed at the plasma membrane and are subsequently internalized by endocytosis. During the late stages of infection, viral replication organelles are represented by large cytopathic vacuoles, where replicase complexes bind to membranes of endolysosomal origin. In addition to viral components, these organelles harbor an unknown number of host proteins. In this study, a fraction of modified lysosomes carrying functionally intact replicase complexes was obtained by feeding Semliki Forest virus (SFV)-infected HeLa cells with dextran-covered magnetic nanoparticles and later magnetically isolating the nanoparticle-containing lysosomes. Stable isotope labeling with amino acids in cell culture combined with quantitative proteomics was used to reveal 78 distinct cellular proteins that were at least 2.5-fold more abundant in replicase complex-carrying vesicles than in vesicles obtained from noninfected cells. These host components included the RNA-binding proteins PCBP1, hnRNP M, hnRNP C, and hnRNP K, which were shown to colocalize with the viral replicase. Silencing of hnRNP M and hnRNP C expression enhanced the replication of SFV, Chikungunya virus (CHIKV), and Sindbis virus (SINV). PCBP1 silencing decreased SFV-mediated protein synthesis, whereas hnRNP K silencing increased this synthesis. Notably, the effect of hnRNP K silencing on CHIKV- and SINV-mediated protein synthesis was opposite to that observed for SFV. This study provides a new approach for analyzing the proteome of the virus replication organelle of positive-strand RNA viruses and helps to elucidate how host RNA-binding proteins exert important but diverse functions during positive-strand RNA viral infection.",,"['Varjak, Margus', 'Saul, Sirle', 'Arike, Liisa', 'Lulla, Aleksei', 'Peil, Lauri', 'Merits, Andres']",,,,
,PMC,Presentation Overrides Specificity: Probing the Plasticity of Alphaviral Proteolytic Activity through Mutational Analysis,http://dx.doi.org/10.1128/JVI.01485-13,PMC3754006,,,"Semliki Forest virus (genus Alphavirus) is an important model for studying regulated nonstructural (ns) polyprotein processing. In this study, we evaluated the strictness of the previously outlined cleavage rules, accounting for the timing and outcome of each of three cleavages within the ns polyprotein P1234, and assessed the significance of residues P6 to P4 within the cleavage sites using an alanine scanning approach. The processing of the 1/2 and 3/4 sites was most strongly affected following changes in residues P5 and P4, respectively. However, none of the mutations had a detectable effect on the processing of the 2/3 site. An analysis of recombinant viruses bearing combinations of mutations in cleavage sites revealed tolerance toward the cooccurrence of native and mutated cleavage sites within the same polyprotein, suggesting a remarkable plasticity of the protease recognition pocket. Even in a virus in which all of the cleavage sequences were replaced with alanines in the P6, P5, and P4 positions, the processing pattern was largely preserved, without leading to reversion of cleavage site mutations. Instead, the emergence of second-site mutations was identified, among which Q706R/L in nsP2 was confirmed to be associated with the recognition of the P4 position within the modified cleavage sites. Our results imply that the spatial arrangement of the viral replication complex inherently contributes to scissile-site presentation for the protease, alleviating stringent sequence recognition requirements yet ensuring the precision and the correct order of processing events. Obtaining a proper understanding of the consequences of cleavage site manipulations may provide new tools for taming alphaviruses.",,"['Lulla, Valeria', 'Karo-Astover, Liis', 'Rausalu, Kai', 'Merits, Andres', 'Lulla, Aleksei']",,,,
,PMC,Zebrafish ISG15 Exerts a Strong Antiviral Activity against RNA and DNA Viruses and Regulates the Interferon Response,http://dx.doi.org/10.1128/JVI.01294-12,PMC3753986,,,"ISG15, a 15-kDa interferon-induced protein that participates in antiviral defenses of mammals, is highly conserved among vertebrates. In fish, as in mammals, viral infection and interferon treatment induce isg15 expression. The two ubiquitin-like domains of ISG15 and the presence of a consensus LRLRGG sequence in the C-terminal region, which is required for the covalent conjugation to a substrate protein, are also conserved in fish. Our data demonstrate that overexpression of zebrafish ISG15 (zf-ISG15) in EPC cells is sufficient to inhibit viral infection by RNA viruses belonging to the genera Novirhabdovirus and Birnavirus and by DNA viruses of the genus Iridovirus. In coexpression experiments with IHNV proteins, we demonstrate specific ISGylation of phosphoprotein and nonvirion protein. Mutation of the glycine residues in the consensus LRLRGG motif abolishes zf-ISG15 conjugation to these proteins and the cellular protection against viral infection, thus connecting ISGylation and ISG15-dependent viral restriction. Additionally, zf-ISG15 overexpression triggers induction of the rig-I and viperin genes as well as, to a lesser extent, the IFN gene. Overall, our data demonstrate the antiviral effect of a fish ISG15 protein, revealing the conservation among vertebrates of an ISGylation mechanism likely directed against viruses. Furthermore, our findings indicate that zf-ISG15 affects the IFN system at several levels, and its study shall shed further light on the evolution of the complex regulation of the innate antiviral response in vertebrate cells.",,"['Langevin, C.', 'van der Aa, L. M.', 'Houel, A.', 'Torhy, C.', 'Briolat, V.', 'Lunazzi, A.', 'Harmache, A.', 'Bremont, M.', 'Levraud, J.-P.', 'Boudinot, P.']",,,,
,PMC,A cost-benefit analysis of the physical mechanisms of membrane curvature,http://dx.doi.org/10.1038/ncb2832,PMC3813008,,,"Many cellular membrane-bound structures exhibit distinct curvature that is driven by the physical properties of their lipid and protein constituents. Here we review how cells manipulate and control this curvature in the context of dynamic events such as vesicle-mediated membrane traffic. Lipids and cargo proteins each contribute energetic barriers that must be overcome during vesicle formation. In contrast, protein coats and their associated accessory proteins drive membrane bending using a variety of interdependent physical mechanisms. We survey the energetic costs and drivers involved in membrane curvature, drawing a contrast between the stochastic contributions of molecular crowding and the deterministic assembly of protein coats. These basic principles also apply to other cellular examples of membrane bending events, including important disease-related problems like viral egress.",,"['Stachowiak, Jeanne C.', 'Brodsky, Frances M.', 'Miller, Elizabeth A.']",,,,
,PMC,"Viral Etiologies of Infant Bronchiolitis, Croup, and Upper Respiratory Illness during Four Consecutive Years",http://dx.doi.org/10.1097/INF.0b013e31829b7e43,PMC3880140,,,"BACKGROUND: Prospective data on viral etiology and clinical characteristics of bronchiolitis and upper respiratory illness in infants is limited. METHODS: This prospective cohort enrolled previously healthy term infants during inpatient or outpatient visits for acute upper respiratory illness (URI) or bronchiolitis during September - May 2004–2008. Illness severity was determined using an ordinal bronchiolitis severity score. Common respiratory viruses were identified by real-time RT-PCR. RESULTS: Of 648 infants, 67% were enrolled during inpatient visits and 33% during outpatient visits. Seventy percent had bronchiolitis, 3% croup, and 27% URI. Among infants with bronchiolitis, 76% had RSV, 18% HRV, 10% influenza, 2% coronavirus, 3% HMPV, and 1% PIV. Among infants with croup, 39% had HRV, 28% PIV, 28% RSV, 11% influenza, 6% coronavirus, and none HMPV. Among infants with URI, 46% had HRV, 14% RSV, 12% influenza, 7% coronavirus, 6% PIV, and 4% HMPV. Individual viruses exhibited distinct seasonal, demographic, and clinical expression. CONCLUSIONS: The most common infections among infants seeking care in unscheduled medical visits for URI or bronchiolitis were RSV and HRV. Demographic differences were observed between patients with different viruses, suggesting that host and viral factors play a role in phenotypic expression of viral illness.",,"['Miller, E. Kathryn', 'Gebretsadik, Tebeb', 'Carroll, Kecia N.', 'Dupont, William D.', 'Mohamed, Yassir A.', 'Morin, Laura-Lee', 'Heil, Luke', 'Minton, Patricia A.', 'Woodward, Kimberly', 'Liu, Zhouwen', 'Hartert, Tina V.', 'Williams, John V.']",,,,
,PMC,Evaluation of the Novel Respiratory Virus Surveillance Program: Pediatric Early Warning Sentinel Surveillance (PEWSS),,PMC3730010,,,"OBJECTIVES: Infections caused by respiratory viruses are associated with recurrent epidemics and widespread morbidity and mortality. Routine surveillance of these pathogens is necessary to determine virus activity, monitor for changes in circulating strains, and plan for public health preparedness. The Southern Nevada Health District in Las Vegas, Nevada, recruited five pediatric medical practices to serve as sentinel sites for the Pediatric Early Warning Sentinel Surveillance (PEWSS) program. METHODS: Sentinel staff collected specimens throughout the year from ill children who met the influenza-like illness case definition and submitted specimens to the Southern Nevada Public Health Laboratory for molecular testing for influenza and six non-influenza viruses. RESULTS: Laboratory results were analyzed and reported to the medical and general communities in weekly bulletins year-round. PEWSS data were also used to establish viral respiratory seasonal baselines and in influenza vaccination campaigns. The surveillance program was evaluated using the Centers for Disease Control and Prevention's (CDC's) Updated Guidelines for Evaluating Public Health Surveillance Systems. PEWSS met three of six program usefulness criteria and seven of nine surveillance system attributes, which exceeded the CDC Guidelines evaluation criteria for a useful and complete public health surveillance program. CONCLUSION: We found that PEWSS is a useful and complete public health surveillance system that is simple, flexible, accessible, and stable.",,"['Armour, Patricia A.', 'Nguyen, Linh M.', 'Lutman, Michelle L.', 'Middaugh, John P.']",,,,
,PMC,Tyrosine Phosphorylation of CD13 Regulates Inflammatory Cell-Cell Adhesion and Monocyte Trafficking,http://dx.doi.org/10.4049/jimmunol.1301348,PMC3810388,,,"CD13 is a large cell surface peptidase expressed on the monocytes and activated endothelial cells important for homing to and resolving the damaged tissue at sites of injury. We have previously shown that crosslinking of human monocytic CD13 with activating antibodies induces strong adhesion to endothelial cells in a tyrosine kinase- and microtubule-dependent manner. In the current study we examined the molecular mechanisms underlying these observations in vitro and in vivo. We found that crosslinking of CD13 on U937 monocytic cells induced phosphorylation of a number of proteins, including Src, FAK and ERK and inhibition of these abrogated CD13-dependent adhesion. We found that CD13 itself was phosphorylated in a Src dependent manner, an unexpected finding as its 7 amino acid cytoplasmic tail was assumed to be inert. Furthermore, CD13 was constitutively associated with the scaffolding protein IQGAP1 and CD13 crosslinkinginduced complex formation with the actin-binding protein α-actinin, linking membrane-bound CD13 to the cytoskeleton, further supporting CD13 as an inflammatory adhesion molecule. Mechanistically, mutation of the conserved CD13 cytoplasmic tyrosine to phenylalanine abrogated adhesion, Src, FAK and ERK phosphorylation and cytoskeletal alterations upon antibody crosslinking. Finally, CD13 was phosphorylated in isolated murine inflammatory peritoneal exudate cells and adoptive transfer of monocytic cell lines engineered to express the mutant CD13 were severely impaired in their ability to migrate into the inflamed peritoneum, confirming that CD13 phosphorylation is relevant to inflammatory cell trafficking in vivo. Therefore, this study identifies CD13 as a novel, direct activator of intracellular signaling pathways in pathophysiological conditions.",,"['Subramani, Jaganathan', 'Ghosh, Mallika', 'Rahman, M. Mamunur', 'Caromile, Leslie A.', 'Gerber, Claire', 'Rezaul, Karim', 'Han, David K.', 'Shapiro, Linda H.']",,,,
,PMC,ICAM-1 dependent homotypic aggregates regulate CD8 T cell effector function and differentiation during T cell activation(),http://dx.doi.org/10.4049/jimmunol.1201954,PMC3803108,,,"A hallmark of T cell activation in vitro and in vivo is the clustering of T cells with each other via interaction of the LFA-1 integrin with ICAM-1. The functional significance of these homotypic aggregates in regulating T cell function remains unknown. We used an APC-free in vitro activation system to demonstrate that stimulation of purified naïve CD8 T cells results in enhanced expression of ICAM-1 on T cells that is sustained by the inflammatory cytokine IL-12 and associated with robust T cell aggregates. ICAM-1 deficient CD8 T cells proliferate normally but demonstrate a striking failure to aggregate. Interestingly, loss of ICAM-1 expression results in elevated levels of interferon-γ (IFN-γ) and Granzyme B, as well as enhanced cytotoxicity. Similar results were obtained when anti-LFA-1 antibody was used to block the clustering of wild-type T cells. ICAM-1 ligation is not required for IFN-γ regulation, as clustering of ICAM-1 deficient CD8 T cells with wild-type T cells reduces IFN-γ expression. Analysis using a fluorescent reporter that monitors TCR signal strength indicates that T cell clustering limits T cell exposure to antigen during activation. Furthermore, T cell clustering promotes the upregulation of the CTLA-4 inhibitory receptor and the downregulation of eomesodermin, which controls effector molecule expression. Activation of ICAM-1 deficient CD8 T cells in vivo results in an enhanced percentage of KLRG-1(+) T cells indicative of short-lived effectors. These results suggest that T cell clustering represents a mechanism that allows continued proliferation but regulates T cell effector function and differentiation.",,"['Zumwalde, Nicholas A.', 'Domae, Eisuke', 'Mescher, Matthew F.', 'Shimizu, Yoji']",,,,
,PMC,IFITM3 and Susceptibility to Respiratory Viral Infections in the Community,http://dx.doi.org/10.1093/infdis/jit468,PMC3952664,,,"Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM 1,2, and 3) are viral restriction factors that mediate cellular resistance to several viruses. We have genotyped a possible splice-site altering single-nucleotide polymorphism (rs12252) in the IFITM3 gene in 34 patients with H1N1 influenza and severe pneumonia, and >5000 individuals comprising patients with community-acquired mild lower respiratory tract infection and matched controls of Caucasian ancestry. We found evidence of an association between rs12252 rare allele homozygotes and susceptibility to mild influenza (in patients attending primary care) but could not confirm a previously reported association between this single-nucleotide polymorphism and susceptibility to severe H1N1 infection.",,"['Mills, Tara C.', 'Rautanen, Anna', 'Elliott, Katherine S.', 'Parks, Tom', 'Naranbhai, Vivek', 'Ieven, Margareta M.', 'Butler, Christopher C.', 'Little, Paul', 'Verheij, Theo', 'Garrard, Chris S.', 'Hinds, Charles', 'Goossens, Herman', 'Chapman, Stephen', 'Hill, Adrian V. S.']",,,,
,PMC,Interleukin-1 receptor-associated kinase M (IRAK-M) promotes human rhinovirus infection in lung epithelial cells via the autophagic pathway,http://dx.doi.org/10.1016/j.virol.2013.08.005,PMC3804030,,,"Human rhinovirus (HRV) is the most common viral etiology in acute exacerbations of asthma. However, the exact mechanisms underlying HRV infection in allergic airways are poorly understood. IL-13 increases interleukin-1 receptor associated kinase M (IRAK-M) and subsequently inhibits airway innate immunity against bacteria. However, the role of IRAK-M in lung HRV infection remains unclear. Here, we provide the first evidence that IRAK-M over-expression promotes lung epithelial HRV-16 replication and autophagy, but inhibits HRV-16-induced IFN-β and IFN-λ1 expression. Inhibiting autophagy reduces HRV-16 replication. Exogenous IFN-β and IFN-λ1 inhibit autophagy and HRV-16 replication. Our data indicate the enhancing effect of IRAK-M on epithelial HRV-16 infection, which is partly through the autophagic pathway. Impaired anti-viral interferon production may serve as a direct or an indirect (e.g., autophagy) mechanism of enhanced HRV-16 infection by IRAK-M over-expression. Targeting autophagic pathway or administrating anti-viral interferons may prevent or attenuate viral (e.g., HRV-16) infections in allergic airways.",,"['Wu, Qun', 'van Dyk, Linda F.', 'Jiang, Di', 'Dakhama, Azzeddine', 'Li, Liwu', 'White, Steven R.', 'Gross, Ashley', 'Chu, Hong Wei']",,,,
,PMC,Receptor recognition and cross-species infections of SARS coronavirus,http://dx.doi.org/10.1016/j.antiviral.2013.08.014,PMC3840050,,,"Receptor recognition is a major determinant of the host range, cross-species infections, and pathogenesis of the severe acute respiratory syndrome coronavirus (SARS-CoV). A defined receptor-binding domain (RBD) in the SARS-CoV spike protein specifically recognizes its host receptor, angiotensin-converting enzyme 2 (ACE2). This article reviews the latest knowledge about how RBDs from different SARS-CoV strains interact with ACE2 from several animal species. Detailed research on these RBD/ACE2 interactions has established important principles on host receptor adaptations, cross-species infections, and future evolution of SARS-CoV. These principles may apply to other emerging animal viruses, including the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV). This paper forms part of a series of invited articles in Antiviral Research on “From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.”",,"Li, Fang",,,,
,PMC,Transmission dynamics of the 2009 influenza A (H1N1) pandemic in India: The impact of holiday-related school closure,http://dx.doi.org/10.1016/j.epidem.2013.08.001,PMC4088951,,,"The role of social-distancing measures, such as school closures, is a controversial aspect of pandemic mitigation planning. However, the timing of 2009 pandemic provides a natural experiment for evaluating the impact of school closure during holidays on influenza transmission. To quantify the transmission intensity of the influenza A (H1N1) pdm’09 in India, by estimating the time varying reproduction number (R(t)) and correlating the temporal changes in the estimates of R(t) for different regions of India with the timing of school holidays. We used daily lab-confirmed case reports of influenza A (H1N1) pdm’09 in India (during 17 May’09 to 17 May’10), stratified by regions. We estimated the transmissibility of the pandemic for different regions from these time-series, using Bayesian methods applied to a branching process model of disease spread and correlated the resulting estimates with the timing of school holidays in each region. The North-west region experienced two notable waves, with the peak of the first wave coinciding with the start of a 4 week school holiday (September-October’09). In the southern region the two waves were less clear cut, though again the first peak of the first wave coincided with the start of school holidays – albeit of less than 2 weeks duration (August’09). Our analysis suggests that the school holidays had a significant influence on the epidemiology of the 2009 pandemic in India. We estimate that school holidays reduced the reproduction number by 14%–27% in different regions of India, relative to levels seen outside holiday periods. The estimates of the reproduction number obtained (with peak R values below 1.5) are compatible with those reported from other regions of the world. This work reinforces past studies showing the significant impact of school holidays on spread of 2009 pandemic virus, and by inference the role of contact patterns in children on transmission.",,"['Taslim Ali, Sheikh', 'Kadi, A. S.', 'Ferguson, Neil M.']",,,,
,PMC,Healthcare worker compliance with seasonal and pandemic influenza vaccination,http://dx.doi.org/10.1111/irv.12088,PMC5909401,,,"Healthcare workers (HCWs) can be an important source of transmission of influenza to patients and family members, and their well‐being is fundamental to the maintenance of healthcare services during influenza outbreaks and pandemics. Unfortunately, studies have shown consistently low levels of compliance with influenza vaccination among HCWs, a finding that became particularly pronounced during recent pandemic vaccination campaigns. Among the variables associated with vaccine acceptance in this group are demographic factors, fears and concerns over vaccine safety and efficacy, perceptions of risk and personal vulnerability, past vaccination behaviours and experience with influenza illness, as well as certain situational and organisational constructs. We report the findings of a review of the literature on these factors and highlight some important challenges in interpreting the data. In particular, we point out the need for longitudinal study designs, as well as focused research and interventions that are adapted to the most resistant HCW groups. Multi‐pronged strategies are an important step forward in ensuring that future influenza vaccination campaigns, whether directed at seasonal or pandemic strains, will be successful in ensuring broad coverage among HCWs.",,"['Bellia, Claire', 'Setbon, Michel', 'Zylberman, Patrick', 'Flahault, Antoine']",,,,
,PMC,Clinical care for severe influenza and other severe illness in resource‐limited settings: the need for evidence and guidelines,http://dx.doi.org/10.1111/irv.12086,PMC5909399,,,"The 2009 influenza A (H1N1) pandemic highlighted the importance of quality hospital care of the severely ill, yet there is evidence that the impact of the 2009 pandemic was highest in low‐ and middle‐income countries with fewer resources. Recent data indicate that death and suffering from seasonal influenza and severe illness in general are increased in resource‐limited settings. However, there are limited clinical data and guidelines for the management of influenza and other severe illness in these settings. Life‐saving supportive care through syndromic case management is used successfully in high‐resource intensive care units and in global programs such as the Integrated Management of Childhood Illness (IMCI). While there are a variety of challenges to the management of the severely ill in resource‐limited settings, several new international initiatives have begun to develop syndromic management strategies for these environments, including the World Health Organization's Integrated Management of Adult and Adolescent Illness Program. These standardized clinical guidelines emphasize syndromic case management and do not require high‐resource intensive care units. These efforts must be enhanced by quality clinical research to provide missing evidence and to refine recommendations, which must be carefully integrated into existing healthcare systems. Realizing a sustainable, global impact on death and suffering due to severe influenza and other severe illness necessitates an ongoing and concerted international effort to iteratively generate, implement, and evaluate best‐practice management guidelines for use in resource‐limited settings.",,"['Ortiz, Justin R.', 'Jacob, Shevin T.', 'Eoin West, T.']",,,,
,PMC,Bacterial and viral infections associated with influenza,http://dx.doi.org/10.1111/irv.12089,PMC5909385,,,"Influenza‐associated bacterial and viral infections are responsible for high levels of morbidity and death during pandemic and seasonal influenza episodes. A review was undertaken to assess and evaluate the incidence, epidemiology, aetiology, clinical importance and impact of bacterial and viral co‐infection and secondary infection associated with influenza. A review was carried out of published articles covering bacterial and viral infections associated with pandemic and seasonal influenza between 1918 and 2009 (and published through December 2011) to include both pulmonary and extra‐pulmonary infections. While pneumococcal infection remains the predominant cause of bacterial pneumonia, the review highlights the importance of other co‐ and secondary bacterial and viral infections associated with influenza, and the emergence of newly identified dual infections associated with the 2009 H1N1 pandemic strain. Severe influenza‐associated pneumonia is often bacterial and will necessitate antibiotic treatment. In addition to the well‐known bacterial causes, less common bacteria such as Legionella pneumophila may also be associated with influenza when new influenza strains emerge. This review should provide clinicians with an overview of the range of bacterial and viral co‐ or secondary infections that could present with influenza illness.",,"['Joseph, Carol', 'Togawa, Yu', 'Shindo, Nahoko']",,,,
,PMC,Non-encapsidation Activities of the Capsid Proteins of Positive-strand RNA Viruses,http://dx.doi.org/10.1016/j.virol.2013.07.023,PMC3818703,,,"Viral capsid proteins (CPs) are characterized by their role in forming protective shells around viral genomes. However, CPs have additional and important roles in the virus infection cycles and in the cellular response to infection. These activities involve CP binding to RNAs in both sequence-specific and nonspecific manners as well as association with other proteins. This review focuses on CPs of both plant and animal-infecting viruses with positive-strand RNA genomes. We summarize the structural features of CPs and describe their modulatory roles in viral translation, RNA-dependent RNA synthesis, and host defense responses.",,"['Ni, Peng', 'Kao, C. Cheng']",,,,
,PMC,To fuse or not to fuse: What is your purpose?,http://dx.doi.org/10.1002/pro.2356,PMC3831663,,,"Since the dawn of time, or at least the dawn of recombinant DNA technology (which for many of today's scientists is the same thing), investigators have been cloning and expressing heterologous proteins in a variety of different cells for a variety of different reasons. These range from cell biological studies looking at protein-protein interactions, post-translational modifications, and regulation, to laboratory-scale production in support of biochemical, biophysical, and structural studies, to large scale production of potential biotherapeutics. In parallel, fusion-tag technology has grown-up to facilitate microscale purification (pull-downs), protein visualization (epitope tags), enhanced expression and solubility (protein partners, e.g., GST, MBP, TRX, and SUMO), and generic purification (e.g., His-tags, streptag, and FLAG™-tag). Frequently, these latter two goals are combined in a single fusion partner. In this review, we examine the most commonly used fusion methodologies from the perspective of the ultimate use of the tagged protein. That is, what are the most commonly used fusion partners for pull-downs, for structural studies, for production of active proteins, or for large-scale purification? What are the advantages and limitations of each? This review is not meant to be exhaustive and the approach undoubtedly reflects the experiences and interests of the authors. For the sake of brevity, we have largely ignored epitope tags although they receive wide use in cell biology for immunopreciptation.",,"['Bell, Mark R', 'Engleka, Mark J', 'Malik, Asim', 'Strickler, James E']",,,,
,PMC,Physiological functions and clinical implications of fibrinogen-like 2: A review,http://dx.doi.org/10.5495/wjcid.v3.i3.37,PMC4495006,,,"Fibrinogen-like 2 (FGL2) encompasses a transmembrane (mFGL2) and a soluble (sFGL2) form with differential tertiary structure and biological activities. Typically, mFGL2 functions as prothrombinase that is capable of initiating coagulation in tissue without activation of the blood clotting cascade, whereas sFGL2 largely acts as an immunosuppressor that can repress proliferation of alloreactive T lymphocytes and maturation of bone marrow dendritic cells. Protein sequences of FGL2 exhibit evolutionary conservation across wide variety of species, especially at the carboxyl terminus that contains fibrinogen related domain (FRED). The FRED of FGL2 confers specificity and complexity in the action of FGL2, including receptor recognition, calcium affiliation, and substrate binding. Constitutive expression of FGL2 during embryogenesis and in mature tissues suggests FGL2 might be physiologically important. However, excessive induction of FGL2 under certain medical conditions (e.g., pathogen invasion) could trigger complement activation, inflammatory response, cellular apoptosis, and immune dysfunctions. On the other hand, complete absence of FGL2 is also detrimental as lack of FGL2 can cause autoimmune glomerulonephritis and acute cellular rejection of xenografts. All these roles involve mFGL2, sFGL2, or their combination. Although it is not clear how mFGL2 is cleaved off its host cells and secreted into the blood, circulating sFGL2 has been found correlated with disease severity and viral loading among patients with human hepatitis B virus or hepatitis C virus infection. Further studies are warranted to understand how FGL2 expression is regulated under physiological and pathological conditions. Even more interesting is to determine whether mFGL2 can fulfill an immunoregulatory role through its FRED at carboxyl end of the molecule and, and vice versa, whether sFGL2 is procoagulant upon binding to a target cell. Knowledge in this area should shed light on development of sFGL2 as an alternative immunosuppressive agent for organ transplantation or as a biomarker for predicting disease progression, monitoring therapeutic effects, and targeting FGL2 for repression in ameliorating fulminant viral hepatitis.",,"['Yang, Genyan', 'Hooper, W Craig']",,,,
,PMC,The Emergent Discipline of Health Web Science,http://dx.doi.org/10.2196/jmir.2499,PMC3758025,23968998,CC BY,"The transformative power of the Internet on all aspects of daily life, including health care, has been widely recognized both in the scientific literature and in public discourse. Viewed through the various lenses of diverse academic disciplines, these transformations reveal opportunities realized, the promise of future advances, and even potential problems created by the penetration of the World Wide Web for both individuals and for society at large. Discussions about the clinical and health research implications of the widespread adoption of information technologies, including the Internet, have been subsumed under the disciplinary label of Medicine 2.0. More recently, however, multi-disciplinary research has emerged that is focused on the achievement and promise of the Web itself, as it relates to healthcare issues. In this paper, we explore and interrogate the contributions of the burgeoning field of Web Science in relation to health maintenance, health care, and health policy. From this, we introduce Health Web Science as a subdiscipline of Web Science, distinct from but overlapping with Medicine 2.0. This paper builds on the presentations and subsequent interdisciplinary dialogue that developed among Web-oriented investigators present at the 2012 Medicine 2.0 Conference in Boston, Massachusetts.",2013 Aug 22,"['Luciano, Joanne S', 'Cumming, Grant P', 'Wilkinson, Mark D', 'Kahana, Eva']",J Med Internet Res,,,
,PMC,New insights into the aryl hydrocarbon receptor as a modulator of host responses to infection,http://dx.doi.org/10.1007/s00281-013-0395-3,PMC3808126,,,"The host response to infection is known to be influenced by many factors, including genetics, nutritional status, age, as well as drug and chemical exposures. Recent advances reveal that the aryl hydrocarbon receptor (AhR) modulates aspects of the innate and adaptive immune response to viral, bacterial, and parasitic organisms. Although many of these observations were made using the high affinity but poorly metabolized AhR agonist TCDD, not all of effects are detrimental to the host. Sometimes AhR activation, even with TCDD, was beneficial and improved host resistance and survival. A similar dichotomy is observed in infected AhR-deficient mice, wherein absence of functional AhR sometimes, but not always, alters host resistance. When examined in their totality, current data indicate that AhR controls multiple regulatory pathways that converge with infection-associated signals, and depending on the context (e.g., type of pathogen, site of infection) lead to distinct outcomes. This creates numerous exciting opportunities to harness the immunomodulatory action of AhR to transform host responses to infection. Moreover, since many of the mechanisms cued in response to infectious agents are pivotal in the context of other diseases, there is much to be learned about AhR's cellular targets and molecular mechanisms of action.",,"['Lawrence, B. Paige', 'Vorderstrasse, Beth A.']",,,,
,PMC,A Unique Report: Development of Super Anti-Human IgG Monoclone with Optical Density Over Than 3,http://dx.doi.org/10.5681/apb.2013.054,PMC3848219,,,"Purpose: Monoclonal antibodies and related conjugates are key reagents used in biomedical researches as well as, in treatment, purification and diagnosis of infectious and non- infectious diseases. Methods: Balb/c mice were immunized with purified human IgG. Spleen cells of the most immune mouse were fused with SP2/0 in the presence of Poly Ethylene Glycol (PEG). Supernatant of hybridoma cells was screened for detection of antibody by ELISA. Then, the sample was assessed for cross-reactivity with IgM & IgA by ELISA and confirmed by immunoblotting. The subclasses of the selected mAbs were determined. The best clone was injected intraperitoneally to some pristane-injected mice. Anti-IgG mAb was purified from the animals' ascitic fluid by Ion exchange chromatography and then, mAb was conjugated with HRP. Results: In the present study, over than 50 clones were obtained that 1 clone had optical density over than 3. We named this clone as supermonoclone which was selected for limiting dilution. The result of the immunoblotting, showed sharp band in IgG position and did not show any band in IgM&IgA position. Conclusion: Based on the findings of this study, the conjugated monoclonal antibody could have application in diagnosis of infectious diseases like Toxoplasmosis, Rubella and IgG class of other infectious and non- infectious diseases.",,"['Aghebati Maleki, Leili', 'Baradaran, Behzad', 'Abdolalizadeh, Jalal', 'Ezzatifar, Fatemeh', 'Majidi, Jafar']",,,,
,PMC,ACE2 alterations in kidney disease,http://dx.doi.org/10.1093/ndt/gft320,PMC3811059,,,"Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that degrades angiotensin (Ang) II to Ang-(1–7). ACE2 is highly expressed within the kidneys, it is largely localized in tubular epithelial cells and less prominently in glomerular epithelial cells and in the renal vasculature. ACE2 activity has been shown to be altered in diabetic kidney disease, hypertensive renal disease and in different models of kidney injury. There is often a dissociation between tubular and glomerular ACE2 expression, particularly in diabetic kidney disease where ACE2 expression is increased at the tubular level but decreased at the glomerular level. In this review, we will discuss alterations in circulating and renal ACE2 recently described in different renal pathologies and disease models as well as their possible significance.",,"['Soler, María José', 'Wysocki, Jan', 'Batlle, Daniel']",,,,
,PMC,Antenatal betamethasone exposure is associated with lower ANG-(1–7) and increased ACE in the CSF of adult sheep,http://dx.doi.org/10.1152/ajpregu.00321.2013,PMC3798802,,,"Antenatal betamethasone (BM) therapy accelerates lung development in preterm infants but may induce early programming events with long-term cardiovascular consequences. To elucidate these events, we developed a model of programming whereby pregnant ewes are administered BM (2 doses of 0.17 mg/kg) or vehicle at the 80th day of gestation and offspring are delivered at term. BM-exposed (BMX) offspring develop elevated blood pressure; decreased baroreflex sensitivity; and alterations in the circulating, renal, and brain renin-angiotensin systems (RAS) by 6 mo of age. We compared components of the choroid plexus fourth ventricle (ChP4) and cerebral spinal fluid (CSF) RAS between control and BMX male offspring at 6 mo of age. In the choroid plexus, high-molecular-weight renin protein and ANG I-intact angiotensinogen were unchanged between BMX and control animals. Angiotensin-converting enzyme 2 (ACE2) activity was threefold higher than either neprilysin (NEP) or angiotensin 1-converting enzyme (ACE) in control and BMX animals. Moreover, all three enzymes were equally enriched by approximately 2.5-fold in ChP4 brush-border membrane preparations. CSF ANG-(1–7) levels were significantly lower in BMX animals (351.8 ± 76.8 vs. 77.5 ± 29.7 fmol/mg; P < 0.05) and ACE activity was significantly higher (6.6 ± 0.5 vs. 8.9 ± 0.5 fmol·min(−1)·ml(−1); P < 0.05), whereas ACE2 and NEP activities were below measurable limits. A thiol-sensitive peptidase contributed to the majority of ANG-(1–7) metabolism in the CSF, with higher activity in BMX animals. We conclude that in utero BM exposure alters CSF but not ChP RAS components, resulting in lower ANG-(1–7) levels in exposed animals.",,"['Marshall, Allyson C.', 'Shaltout, Hossam A.', 'Pirro, Nancy T.', 'Rose, James C.', 'Diz, Debra I.', 'Chappell, Mark C.']",,,,
,PMC,The role of IL-27 in the induction of anti-tumor cytotoxic T lymphocyte response,,PMC3745435,,,"Cytotoxic T lymphocyte (CTL) response is a critical component of the immune response to tumors, therefore optimal induction of CTL responses to tumor antigens is highly desired for developing efficient cancer immunotherapy. IL-27 is a member of the IL-12 family of cytokines that is comprised of an IL-12 p40-related protein subunit, EBV-induced gene 3 (EBI3), and a p35-related subunit, p28. IL-27 functions through IL-27R and has been shown to have potent anti-tumor activity via activation of a variety of immune components, including anti-tumor CD8(+) T cell responses. However, the exact mechanisms of how IL-27 enhances anti-tumor CD8(+) T cell responses are not fully understood. In this paper we mainly discuss the evidences that suggest novel mechanisms by which IL-27 enhances anti-tumor CTL responses, including IL-27 inhibition of activation-induced cell death; the phenotypes of IL-27-stimulated CTLs; IL-27-induced CTL IL-10/IL-21 production and IL-27-mediated suppression of regulatory T cell responses. These evidences suggest that IL-27 may have a great potential to be utilized in boosting anti-tumor CTL responses in human cancer patients.",,"['Liu, Zhenzhen', 'Yu, Jianhua', 'Carson, William E', 'Bai, Xue-Feng']",,,,
,PMC,A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2013 Recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)(a),http://dx.doi.org/10.1093/cid/cit278,PMC3719886,,,"The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.",,"['Baron, Ellen Jo', 'Miller, J. Michael', 'Weinstein, Melvin P.', 'Richter, Sandra S.', 'Gilligan, Peter H.', 'Thomson, Richard B.', 'Bourbeau, Paul', 'Carroll, Karen C.', 'Kehl, Sue C.', 'Dunne, W. Michael', 'Robinson-Dunn, Barbara', 'Schwartzman, Joseph D.', 'Chapin, Kimberle C.', 'Snyder, James W.', 'Forbes, Betty A.', 'Patel, Robin', 'Rosenblatt, Jon E.', 'Pritt, Bobbi S.']",,,,
,PMC,Postentry Processing of Recombinant Adeno-Associated Virus Type 1 and Transduction of the Ferret Lung Are Altered by a Factor in Airway Secretions,http://dx.doi.org/10.1089/hum.2013.137,PMC3768237,,,"We recently created a cystic fibrosis ferret model that acquires neonatal lung infection. To develop lung gene therapies for this model, we evaluated recombinant adeno-associated virus (rAAV)-mediated gene transfer to the neonatal ferret lung. Unlike in vitro ferret airway epithelial (FAE) cells, in vivo infection of the ferret lung with rAAV1 required proteasome inhibitors to achieve efficient airway transduction. We hypothesized that differences in transduction between these two systems were because of an in vivo secreted factor that alter the transduction biology of rAAV1. Indeed, treatment of rAAV1 with ferret airway secretory fluid (ASF) strongly inhibited rAAV1, but not rAAV2, transduction of primary FAE and HeLa cells. Properties of the ASF inhibitory factor included a strong affinity for the AAV1 capsid, heat-stability, negative charge, and sensitivity to endoproteinase Glu-C. ASF-treated rAAV1 dramatically inhibited apical transduction of FAE ALI cultures (512-fold), while only reducing viral entry by 55-fold, suggesting that postentry processing of virus was influenced by the inhibitor factor. Proteasome inhibitors rescued transduction in the presence of ASF (∼1600-fold) without effecting virus internalization, while proteasome inhibitors only enhanced transduction 45-fold in the absence of ASF. These findings demonstrate that a factor in lung secretions can influence intracellular processing of rAAV1 in a proteasome-dependent fashion.",,"['Yan, Ziying', 'Sun, Xingshen', 'Evans, Idil A.', 'Tyler, Scott R.', 'Song, Yi', 'Liu, Xiaoming', 'Sui, Hongshu', 'Engelhardt, John F.']",,,,
,PMC,Potential role of viruses in white plague coral disease,http://dx.doi.org/10.1038/ismej.2013.137,PMC3906806,,,"White plague (WP)-like diseases of tropical corals are implicated in reef decline worldwide, although their etiological cause is generally unknown. Studies thus far have focused on bacterial or eukaryotic pathogens as the source of these diseases; no studies have examined the role of viruses. Using a combination of transmission electron microscopy (TEM) and 454 pyrosequencing, we compared 24 viral metagenomes generated from Montastraea annularis corals showing signs of WP-like disease and/or bleaching, control conspecific corals, and adjacent seawater. TEM was used for visual inspection of diseased coral tissue. No bacteria were visually identified within diseased coral tissues, but viral particles and sequence similarities to eukaryotic circular Rep-encoding single-stranded DNA viruses and their associated satellites (SCSDVs) were abundant in WP diseased tissues. In contrast, sequence similarities to SCSDVs were not found in any healthy coral tissues, suggesting SCSDVs might have a role in WP disease. Furthermore, Herpesviridae gene signatures dominated healthy tissues, corroborating reports that herpes-like viruses infect all corals. Nucleocytoplasmic large DNA virus (NCLDV) sequences, similar to those recently identified in cultures of Symbiodinium (the algal symbionts of corals), were most common in bleached corals. This finding further implicates that these NCLDV viruses may have a role in bleaching, as suggested in previous studies. This study determined that a specific group of viruses is associated with diseased Caribbean corals and highlights the potential for viral disease in regional coral reef decline.",,"['Soffer, Nitzan', 'Brandt, Marilyn E', 'Correa, Adrienne MS', 'Smith, Tyler B', 'Thurber, Rebecca Vega']",,,,
,PMC,Spiking the MERS-coronavirus receptor,http://dx.doi.org/10.1038/cr.2013.108,PMC3760624,,,"A novel coronavirus, the Middle East respiratory syndrome coronavirus, recently emerged through zoonotic transmission, causing a severe lower respiratory tract infection in humans. In two recent papers, one published in Cell Research, the crystal structure of the viral receptor-binding domain in complex with the host CD26/dipeptidyl peptidase 4 receptor has now been characterized.",,"['Bosch, Berend Jan', 'Raj, V Stalin', 'Haagmans, Bart L']",,,,
,PMC,Viral Pathogens and Acute Lung Injury: Investigations Inspired by the SARS Epidemic and the 2009 H1N1 Influenza Pandemic,http://dx.doi.org/10.1055/s-0033-1351122,PMC4045622,,,"Acute viral pneumonia is an important cause of acute lung injury (ALI), although not enough is known about the exact incidence of viral infection in ALI. Polymerase chain reaction-based assays, direct fluorescent antigen (DFA) assays, and viral cultures can detect viruses in samples from the human respiratory tract, but the presence of the virus does not prove it to be a pathogen, nor does it give information regarding the interaction of viruses with the host immune response and bacterial flora of the respiratory tract. The severe acute respiratory syndrome (SARS) epidemic and the 2009 H1N1 influenza pandemic provided a better understanding of how viral pathogens mediate lung injury. Although the viruses initially infect the respiratory epithelium, the relative role of epithelial damage and endothelial dysfunction has not been well defined. The inflammatory host immune response to H1N1 infection is a major contributor to lung injury. The SARS coronavirus causes lung injury and inflammation in part through actions on the nonclassical renin angiotensin pathway. The lessons learned from the pandemic outbreaks of SARS coronavirus and H1N1 capture key principles of virally mediated ALI. There are pathogen-specific pathways underlying virally mediated ALI that converge onto a common end pathway resulting in diffuse alveolar damage. In terms of therapy, lung protective ventilation is the cornerstone of supportive care. There is little evidence that corticosteroids are beneficial, and they might be harmful. Future therapeutic strategies may be targeted to specific pathogens, the pathogenetic pathways in the host immune response, or enhancing repair and regeneration of tissue damage.",,"['Hendrickson, Carolyn M.', 'Matthay, Michael A.']",,,,
,PMC,MERS-CoV: the intermediate host identified?,http://dx.doi.org/10.1016/S1473-3099(13)70193-2,PMC4798748,,,,,"['de Wit, Emmie', 'Munster, Vincent J']",,,,
,PMC,Host genetic determinants of influenza pathogenicity,http://dx.doi.org/10.1016/j.coviro.2013.07.005,PMC4127448,,,"Despite effective vaccines, influenza remains a major global health threat due to the morbidity and mortality caused by seasonal epidemics, as well as the 2009 pandemic. Also of profound concern are the rare but potentially catastrophic transmissions of avian influenza to humans, highlighted by a recent H7N9 influenza outbreak. Murine and human studies reveal that the clinical course of influenza is the result of a combination of both host and viral genetic determinants. While viral pathogenicity has long been the subject of intensive efforts, research to elucidate host genetic determinants, particularly human, is now in the ascendant, and the goal of this review is to highlight these recent insights.",,"['Lin, Tsai-Yu', 'Brass, Abraham L.']",,,,
,PMC,IL-12Rβ1 deficiency: mutation update and description of the IL12RB1 variation database,http://dx.doi.org/10.1002/humu.22380,PMC4104692,,,"IL-12Rβ1 deficiency is an autosomal recessive disorder characterized by predisposition to recurrent and/or severe infections caused by otherwise poorly pathogenic mycobacteria and salmonella. IL-12Rβ1 is a receptor chain of both the IL-12 and the IL-23 receptor and deficiency of IL-12Rβ1 thus abolishes both IL-12 and IL-23 signaling. IL-12Rβ1 deficiency is caused by bi-allelic mutations in the IL12RB1 gene. Mutations resulting in premature stop codons, such as nonsense, frame shift, and splice site mutations, represent the majority of IL-12Rβ1 deficiency causing mutations (66%; 46/70). Also every other morbid mutation completely inactivates the IL-12Rβ1 protein. In addition to disease-causing mutations, rare and common variations with unknown functional effect have been reported in IL12RB1. All these variants have been deposited in the online IL12RB1 variation database (www.LOVD.nl/IL12RB1). In this article, we review the function of IL-12Rβ1 and molecular genetics of human IL12RB1.",,"['van de Vosse, Esther', 'Haverkamp, Margje H.', 'Ramirez-Alejo, Noe', 'Martinez-Gallo, Mónica', 'Blancas-Galicia, Lizbeth', 'Metin, Ayşe', 'Garty, Ben Zion', 'Sun-Tan, Çağman', 'Broides, Arnon', 'de Paus, Roelof A.', 'Keskin, Özlem', 'Çağdaş, Deniz', 'Tezcan, Ilhan', 'Lopez-Ruzafa, Encarna', 'Aróstegui, Juan I.', 'Levy, Jacov', 'Espinosa-Rosales, Francisco J.', 'Sanal, Özden', 'Santos-Argumedo, Leopoldo', 'Casanova, Jean-Laurent', 'Boisson-Dupuis, Stephanie', 'van Dissel, Jaap T.', 'Bustamante, Jacinta']",,,,
,PMC,Role of genomic and proteomic tools in the study of host–virus interactions and virus evolution,http://dx.doi.org/10.1007/s13337-013-0150-3,PMC3832694,,,"Viruses have short replication cycles and produce genomic variants within a host, a process that seems to adapt to their specific host and also enable them to infect new hosts. The recent emergence of viral genomic variants from the circulating pool within the host population and re-emergence of the old ones are posing serious threat to agriculture, animal husbandry and humanity as a whole. This review assesses the potential role of genomic and proteomic tools that can monitor not only the course of infection and pathogenesis, but also predict the pandemic or zoonotic epidemic potential of a virus in a previously exposed or immunologically naive biological population.",,"Bhattacharjee, Soumen",,,,
,PMC,Evaluation of respiratory protection programs and practices in California hospitals during the 2009–2010 H1N1 influenza pandemic,http://dx.doi.org/10.1016/j.ajic.2013.05.006,PMC4615716,,,"BACKGROUND: Emergence of the novel 2009 influenza A H1N1 virus in California led to an evaluation of hospital respiratory protection programs (RPPs) and practices by the California Department of Public Health during the 2009–2010 influenza season. METHODS: Onsite evaluation of 16 hospitals consisted of interviews with managers and health care workers about RPPs and practices, review of written RPPs, and limited observations of personnel using respirators. Data were analyzed using descriptive statistics. RESULTS: All hospitals had implemented policies requiring the minimum use of N95 filtering facepiece respirators when working with patients with H1N1 virus infection; 95.5% of health care workers (n = 199) reported they would wear at least this level of protection when in close contact with a patient with confirmed or suspected H1N1 virus infection. However, evaluation of written RPPs indicated deficiencies in required areas, most commonly in recordkeeping, designation of a program administrator, program evaluation, employee training, and fit testing procedures. CONCLUSIONS: Health care workers were aware of respiratory protection required when providing care for patients with confirmed or suspected H1N1 virus infection. Hospitals should improve written RPPs, fully implement written procedures, and conduct periodic program evaluation to ensure effectiveness of respirator use for health care worker protection. Increased accessibility of resources tailored for hospital respirator program administrators may be helpful.",,"['Beckman, Stella', 'Materna, Barbara', 'Goldmacher, Suzi', 'Zipprich, Jennifer', 'D’Alessandro, Maryann', 'Novak, Debra', 'Harrison, Robert']",,,,
,PMC,Development of transgenic mice expressing a coronavirus-specific public CD4 T cell receptor,http://dx.doi.org/10.1016/j.jim.2013.07.011,PMC3850057,,,"Mice that are transgenic (Tg) for T cell receptor (TCR) expression are used extensively to analyze longitudinal T cell responses during effector and memory phases of the T cell response. Generation of TCR Tg mice generally requires T cell stimulation and cloning in vitro prior to amplification, processes which introduce biases into selection of the TCR that is ultimately chosen for TCR Tg mouse generation. Here we describe an alternative approach that involves no T cell stimulation or propagation in vitro. We generated mice that were transgenic for a TCR responding to a CD4 T cell epitope (epitope M133) that is immunodominant in mice infected with a neurotropic coronavirus, the JHM strain of mouse hepatitis virus. The CD4 T cell response to epitope M133 is of particular interest because it may be pathogenic, protective or regulatory, depending upon the physiological setting. We applied an iterative process in which we identified a TCR-β chain expressed by all mice that were examined (‘public sequence’). This TCR-β chain was introduced into bone marrow cells with a lentivirus vector, generating TCR-β retrogenic mice. A TCR-α chain that paired with this TCR-β was then identified and used to generate a second set of TCR (α/β) retrogenic mice. After demonstrating that these cells were functional and responded to epitope M133, these TCR chains were used to generate an epitope M133-specific TCR Tg mouse. This method should be generally useful for engineering TCR Tg mice without introduction of bias caused by in vitro manipulation and propagation.",,"['Zhao, Jingxian', 'Fett, Craig', 'Pewe, Lecia', 'Zhao, Jincun', 'Perlman, Stanley']",,,,
,PMC,Clinical Impact of Human Coronaviruses 229E and OC43 Infection in Diverse Adult Populations,http://dx.doi.org/10.1093/infdis/jit393,PMC3805243,,,"Background. The incidence and clinical impact of coronavirus (CoV) infection in elderly persons and those with underlying cardiopulmonary disease over a long duration is not well described. We determined the incidence and clinical impact of 229E and OC43 CoV in this population during 4 consecutive winters, and compared illnesses to influenza A, respiratory syncytial virus, and human metapneumovirus. Methods. CoV 229E and OC43 were detected by reverse transcription polymerase chain reaction and serology in 4 adult populations under surveillance for acute respiratory illness during the winters of 1999–2003. Cohorts included healthy young adults, healthy elderly adults, high-risk adults with underlying cardiopulmonary disease, and a hospitalized group. Results. Three hundred ninety-eight CoV infections were identified, with annual infection rates ranging from 2.8% to 26% in prospective cohorts, and prevalence ranging from 3.3% to 11.1% in the hospitalized cohort. The incidence of infections with each strain was similar, although asymptomatic infection and viral coinfection was significantly more common with 229E than OC43 infection. Although the incidence and clinical manifestations were similar for each strain, OC43-infected subjects tended to seek more medical care, as OC43 was twice as common as 229E among the hospitalized cohort. Conclusions. CoV infections in the elderly are frequent, likely causing substantial medical disease burden.",,"['Walsh, Edward E.', 'Shin, Jae Hyun', 'Falsey, Ann R.']",,,,
,PMC,IL-21 optimizes T cell and humoral responses in the central nervous system during viral encephalitis,http://dx.doi.org/10.1016/j.jneuroim.2013.07.019,PMC3796038,,,"Acute coronavirus encephalomyelitis is controlled by T cells while humoral responses suppress virus persistence. This study defines the contribution of interleukin (IL)-21, a regulator of T and B cell function, to central nervous system (CNS) immunity. IL-21 receptor deficiency did not affect peripheral T cell activation or trafficking, but dampened granzyme B, gamma interferon and IL-10 expression by CNS T cells and reduced serum and intrathecal humoral responses. Viral control was already lost prior to humoral CNS responses, but demyelination remained comparable. These data demonstrate a critical role of IL-21 in regulating CNS immunity, sustaining viral persistence and preventing mortality.",,"['Phares, Timothy W.', 'DiSano, Krista D.', 'Hinton, David R.', 'Hwang, Mihyun', 'Zajac, Allan J.', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.']",,,,
,PMC,Generation of human neutralizing monoclonal antibodies against the 2009 pandemic H1N1 virus from peripheral blood memory B lymphocytes,http://dx.doi.org/10.1038/cmi.2013.25,PMC4003197,,,"The 2009 H1N1 influenza pandemic demonstrated the significance of a global health threat to human beings. Although pandemic H1N1 vaccines have been rapidly developed, passive serotherapy may offer superior immediate protection against infections in children, the elderly and immune-compromised patients during an influenza pandemic. Here, we applied a novel strategy based on Epstein–Barr virus (EBV)-immortalized peripheral blood memory B cells to screen high viral neutralizing monoclonal antibodies (MAbs) from individuals vaccinated with the 2009 pandemic H1N1 vaccine PANFLU.1. Through a massive screen of 13 090 immortalized memory B-cell clones from three selected vaccinees, seven MAbs were identified with both high viral neutralizing capacities and hemagglutination inhibition (HAI) activities against the 2009 pandemic H1N1 viruses. These MAbs may have important clinical implications for passive serotherapy treatments of infected patients with severe respiratory syndrome, especially children, the elderly and immunodeficient individuals. Our successful strategy for generating high-affinity MAbs from EBV-immortalized peripheral blood memory B cells may also be applicable to other infectious or autoimmune diseases.",,"['Wang, Hao', 'Ma, Chi', 'Lu, Yanlai', 'Ji, Xu', 'Pang, Yongsheng', 'Hua, Fang', 'Cui, Lianxian', 'Ba, Denian', 'He, Wei']",,,,
,PMC,Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I,http://dx.doi.org/10.1073/pnas.1303275110,PMC3752242,,,"Induction of a proinflammatory response is the hallmark of host innate defense against invading pathogens. Host recognition of influenza A virus (IAV) infection relies on pattern-recognition receptors, including Toll-like receptor 7 (TLR7) and retinoic acid inducible gene-1 (RIG-I) for the activation of innate-immune responses. Here, we show that following a physiological low dose of IAV infection, viral sensing by either TLR7 or RIG-I induces a proinflammatory program that promotes viral replication. Transfer of bronchoalveolar lavage from infected wild-type mice into the airway of mice deficient in TLR7 and RIG-I pathways was sufficient to restore viral replication efficiency. Comparison of IAV-infected cells revealed that inflammatory mediators elicited by TLR7 and RIG-I signaling recruit viral target cells to the airway, thereby enhancing viral load within the respiratory tract. Our data suggest that IAV uses physiological levels of inflammatory responses for its replicative advantage and highlight the complex interplay between viruses and the host innate-immune responses.",,"['Pang, Iris K.', 'Pillai, Padmini S.', 'Iwasaki, Akiko']",,,,
,PMC,Search strategy has influenced the discovery rate of human viruses,http://dx.doi.org/10.1073/pnas.1307243110,PMC3752202,,,"A widely held concern is that the pace of infectious disease emergence has been increasing. We have analyzed the rate of discovery of pathogenic viruses, the preeminent source of newly discovered causes of human disease, from 1897 through 2010. The rate was highest during 1950–1969, after which it moderated. This general picture masks two distinct trends: for arthropod-borne viruses, which comprised 39% of pathogenic viruses, the discovery rate peaked at three per year during 1960–1969, but subsequently fell nearly to zero by 1980; however, the rate of discovery of nonarboviruses remained stable at about two per year from 1950 through 2010. The period of highest arbovirus discovery coincided with a comprehensive program supported by The Rockefeller Foundation of isolating viruses from humans, animals, and arthropod vectors at field stations in Latin America, Africa, and India. The productivity of this strategy illustrates the importance of location, approach, long-term commitment, and sponsorship in the discovery of emerging pathogens.",,"['Rosenberg, Ronald', 'Johansson, Michael A.', 'Powers, Ann M.', 'Miller, Barry R.']",,,,
,PMC,Role of RNase L in Viral PAMP/Influenza Virus and Cigarette Smoke-induced Inflammation and Remodeling,http://dx.doi.org/10.4049/jimmunol.1300082,PMC3750064,,,"Interactions between cigarette smoke (CS) exposure and viral infection play an important role(s) in the pathogenesis of chronic obstructive pulmonary disease (COPD) and a variety of other disorders. A variety of lines of evidence suggest that this interaction induces exaggerated inflammatory, cytokine and tissue remodeling responses. We hypothesized that the 2′-5′OAS/RNase L system, an innate immune antiviral pathway, plays an important role in the pathogenesis of these exaggerated responses. To test this hypothesis we characterize the activation of 2′-5′ oligoadenylate synthase (OAS) in lungs from mice exposed to CS and viral PAMPs/live virus, alone and in combination. We also evaluated the inflammatory and remodeling responses induced by CS and virus/viral PAMPs in lungs from RNase L null and wild type mice. These studies demonstrate that CS and viral PAMPs/live virus interact in a synergistic manner to stimulate the production of select OAS moieties. They also demonstrate that RNase L plays a critical role in the pathogenesis of the exaggerated inflammatory, fibrotic, emphysematous, apoptotic, TGF-β1 and type I IFN responses induced by CS plus virus/viral PAMP in combination. These studies demonstrate that CS is an important regulator of antiviral innate immunity, highlight novel roles of RNase L in CS plus virus induced inflammation, tissue remodeling, apoptosis and cytokine elaboration and highlight pathways that may be operative in COPD and mechanistically-related disorders.",,"['Zhou, Yang', 'Kang, Min-Jong', 'Jha, Babal Kant', 'Silverman, Robert H.', 'Lee, Chun Geun', 'Elias, Jack A.']",,,,
,PMC,Effectiveness of Border Screening for Detecting Influenza in Arriving Airline Travelers,http://dx.doi.org/10.2105/AJPH.2012.300761,PMC4007855,,,"Objectives. We measured symptom and influenza prevalence, and the effectiveness of symptom and temperature screening for identifying influenza, in arriving international airline travelers. Methods. This cross-sectional study collected data from travelers to Christchurch International Airport, New Zealand, in winter 2008, via a health questionnaire, temperature testing, and respiratory sampling. Results. Forms were returned by 15 976 (68%) travelers. Of these, 17% reported at least 1 influenza symptom, with runny or blocked nose (10%) and cough (8%) most common. Respiratory specimens were obtained from 3769 travelers. Estimated prevalence of influenza was 1.1% (4% among symptomatic, 0.2% among asymptomatic). The sensitivity of screening criteria ranged from 84% for “any symptom” to 3% for a fever of 37.8 °C or greater. The positive predictive value was low for all criteria. Conclusions. Border screening using self-reported symptoms and temperature testing has limitations for preventing pandemic influenza from entering a country. Using “any symptom” or cough would lead to many uninfected people being investigated, yet some infected people would remain undetected. If more specific criteria such as fever were used, most infected people would enter the country despite screening.",,"['Priest, Patricia C.', 'Jennings, Lance C.', 'Duncan, Alasdair R.', 'Brunton, Cheryl R.', 'Baker, Michael G.']",,,,
,PMC,Peripheral Blood Mononuclear Cell Gene Expression in Chronic Obstructive Pulmonary Disease,http://dx.doi.org/10.1165/rcmb.2012-0230OC,PMC3824029,,,"Although most cases of chronic obstructive pulmonary disease (COPD) occur in smokers, only a fraction of smokers develop the disease. We hypothesized distinct molecular signatures for COPD and emphysema in the peripheral blood mononuclear cells (PBMCs) of current and former smokers. To test this hypothesis, we identified and validated PBMC gene expression profiles in smokers with and without COPD. We generated expression data on 136 subjects from the COPDGene study, using Affymetrix U133 2.0 microarrays (Affymetrix, Santa Clara, CA). Multiple linear regression with adjustment for covariates (gender, age, body mass index, family history, smoking status, and pack-years) was used to identify candidate genes, and ingenuity pathway analysis was used to identify candidate pathways. Candidate genes were validated in 149 subjects according to multiplex quantitative real-time polymerase chain reaction, which included 75 subjects not previously profiled. Pathways that were differentially expressed in subjects with COPD and emphysema included those that play a role in the immune system, inflammatory responses, and sphingolipid (ceramide) metabolism. Twenty-six of the 46 candidate genes (e.g., FOXP1, TCF7, and ASAH1) were validated in the independent cohort. Plasma metabolomics was used to identify a novel glycoceramide (galabiosylceramide) as a biomarker of emphysema, supporting the genomic association between acid ceramidase (ASAH1) and emphysema. COPD is a systemic disease whose gene expression signatures in PBMCs could serve as novel diagnostic or therapeutic targets.",,"['Bahr, Timothy M.', 'Hughes, Grant J.', 'Armstrong, Michael', 'Reisdorph, Rick', 'Coldren, Christopher D.', 'Edwards, Michael G.', 'Schnell, Christina', 'Kedl, Ross', 'LaFlamme, Daniel J.', 'Reisdorph, Nichole', 'Kechris, Katerina J.', 'Bowler, Russell P.']",,,,
,PMC,The Griffithsin Dimer Is Required for High-Potency Inhibition of HIV-1: Evidence for Manipulation of the Structure of gp120 as Part of the Griffithsin Dimer Mechanism,http://dx.doi.org/10.1128/AAC.00332-13,PMC3719714,,,"Griffithsin (Grft) is a protein lectin derived from red algae that tightly binds the HIV envelope protein gp120 and effectively inhibits virus infection. This inhibition is due to the binding by Grft of high-mannose saccharides on the surface of gp120. Grft has been shown to be a tight dimer, but the role of the dimer in Grft's anti-HIV function has not been fully explored. To investigate the role of the Grft dimer in anti-HIV function, an obligate dimer of Grft was designed by expressing the protein with a peptide linker between the two subunits. This “Grft-linker-Grft” is a folded protein dimer, apparently nearly identical in structural properties to the wild-type protein. A “one-armed” obligate dimer was also designed (Grft-linker-Grft OneArm), with each of the three carbohydrate binding sites of one subunit mutated while the other subunit remained intact. While both constructed dimers retained the ability to bind gp120 and the viral surface, Grft-linker-Grft OneArm was 84- to 1,010-fold less able to inhibit HIV than wild-type Grft, while Grft-linker-Grft had near-wild-type antiviral potency. Furthermore, while the wild-type protein demonstrated the ability to alter the structure of gp120 by exposing the CD4 binding site, Grft-linker-Grft OneArm largely lost this ability. In experiments to investigate gp120 shedding, it was found that Grft has different effects on gp120 shedding for strains from subtype B and subtype C, and this might correlate with Grft function. Evidence is provided that the dimer form of Grft is critical to the function of this protein in HIV inhibition.",,"['Xue, Jie', 'Hoorelbeke, Bart', 'Kagiampakis, Ioannis', 'Demeler, Borries', 'Balzarini, Jan', 'LiWang, Patricia J.']",,,,
,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.13.010813,PMC3738314,,,,,,,,,
,PMC,Failure-to-Thrive Syndrome Associated with Tumor Formation by Madin–Darby Canine Kidney Cells in Newborn Nude Mice,,PMC3750667,,,"Tumors that formed in newborn nude mice that were inoculated with 10(7) Madin–Darby canine kidney (MDCK) cells were associated with a failure-to-thrive (FTT) syndrome consisting of growth retardation, lethargy, weakness, and dehydration. Scoliosis developed in 41% of affected pups. Pups were symptomatic by week 2; severely affected pups became moribund and required euthanasia within 3 to 4 wk. Mice with FTT were classified into categories of mild, moderate, and severe disease by comparing their weight with that of age-matched normal nude mice. The MDCK-induced tumors were adenocarcinomas that invaded adjacent muscle, connective tissue, and bone; 6 of the 26 pups examined had lung metastases. The induction of FTT did not correlate with cell-line aggressiveness as estimated by histopathology or the efficiency of tumor formation (tumor-forming dose 50% endpoint range = 10(2.8) to 10(7.5)); however, tumor invasion of the paravertebral muscles likely contributed to the scoliosis noted. In contrast to the effect of MDCK cells, tumor formation observed in newborn mice inoculated with highly tumorigenic, human-tumor–derived cell lines was not associated with FTT development. We suggest that tumor formation and FTT are characteristics of these MDCK cell inocula and that FTT represents a new syndrome that may be similar to the cachexia that develops in humans with cancer or other diseases.",,"['Brinster, Lauren R', 'Omeir, Romelda L', 'Foseh, Gideon S', 'Macauley, Juliete N', 'Snoy, Philip J', 'Beren, Joel J', 'Teferedegne, Belete', 'Peden, Keith', 'Lewis, Andrew M']",,,,
,PMC,Establishment of cell line from embryonic tissue of Pipistrellus ceylonicus bat species from India & its susceptibility to different viruses,,PMC3788208,24056599,CC BY-NC-SA,"BACKGROUND & OBJECTIVES: Pipistrellus ceylonicus bat species is widely distributed in South Asia, with additional populations recorded in China and Southeast Asia. Bats are the natural reservoir hosts for a number of emerging zoonotic diseases. Attempts to isolate bat-borne viruses in various terrestrial mammalian cell lines have sometimes been unsuccessful. The bat cell lines are useful in isolation and propagation of many of the viruses harboured by bats. New stable bat cell lines are needed to help such investigations and to assist in the study of bat immunology and virus-host interactions. In this study we made an attempt to develop a cell line from P. ceylonicus bats. METHODS: An effort was made to establish cell line from embryo of P. ceylonicus species of bat after seeding to Dulbecco's modified eagle medium (DMEM) supplemented with 10 per cent foetal bovine serum; a primary cell line was established and designated as NIV-BtEPC. Mitochondrial DNA profile analysis was done using cyt-b and ND-1 gene sequences from the cell line. Phylogenetic tree was constructed using neighbour-joining algorithm for cyt-b and ND-1 genes with 1000-bootstrap replicates. RESULTS: NIV-BtEPC cell line was susceptible to Chandipura (CHPV) and novel adenovirus (BtAdv-RLM) isolated from Rousettus leschenaulti from India but did not support multiplication of a number of Bunyaviruses, Alphaviruses and Flavivirus. This might be useful for isolation of a range of viruses and investigation of unknown aetiological agents. INTERPRETATION & CONCLUSIONS: In this study, a new bat cell line was developed from P. ceylonicus. This cell line was successfully tested for the susceptibility to Chandipura and BtAdv-RLM virus isolated from bats. The approach developed and optimised in this study may be applicable to the other species of bats and this established cell line can be used to facilitate virus isolation and basic research into virus-host interaction.",2013 Aug,"['Mourya, Devendra T.', 'Lakra, Rajen J.', 'Yadav, Pragya D.', 'Tyagi, Preeti', 'Raut, Chandrashekhar G.', 'Shete, Anita M.', 'Singh, Dinesh K.']",Indian J Med Res,,,
,PMC,Viral infection of the lung: Host response and sequelae,http://dx.doi.org/10.1016/j.jaci.2013.06.006,PMC3844062,,,"Because of its essential role in gas exchange and oxygen delivery, the lung has evolved a variety of strategies to control inflammation and maintain homeostasis. Invasion of the lung by pathogens (and in some instances exposure to certain noninfectious particulates) disrupts this equilibrium and triggers a cascade of events aimed at preventing or limiting colonization (and more importantly infection) by pathogenic microorganisms. In this review we focus on viral infection of the lung and summarize recent advances in our understanding of the triggering of innate and adaptive immune responses to viral respiratory tract infection, mechanisms of viral clearance, and the well-recognized consequences of acute viral infection complicating underlying lung diseases, such as asthma.",,"['Yoo, Jae-Kwang', 'Kim, Taeg S.', 'Hufford, Matthew M.', 'Braciale, Thomas J.']",,,,
,PMC,Double-membraned Liposomes Sculpted by Poliovirus 3AB Protein,http://dx.doi.org/10.1074/jbc.M113.498899,PMC3779724,,,"Infection with many positive-strand RNA viruses dramatically remodels cellular membranes, resulting in the accumulation of double-membraned vesicles that resemble cellular autophagosomes. In this study, a single protein encoded by poliovirus, 3AB, is shown to be sufficient to induce the formation of double-membraned liposomes via the invagination of single-membraned liposomes. Poliovirus 3AB is a 109-amino acid protein with a natively unstructured N-terminal domain. HeLa cells transduced with 3AB protein displayed intracellular membrane disruption; specifically, the formation of cytoplasmic invaginations. The ability of a single viral protein to produce structures of similar topology to cellular autophagosomes should facilitate the understanding of both cellular and viral mechanisms for membrane remodeling.",,"['Wang, Jing', 'Ptacek, Jennifer B.', 'Kirkegaard, Karla', 'Bullitt, Esther']",,,,
,PMC,Receptor-binding domain as a target for developing SARS vaccines,http://dx.doi.org/10.3978/j.issn.2072-1439.2013.06.06,PMC3747534,,,"A decade ago, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) caused a global pandemic with a mortality rate of 10%. Reports of recent outbreaks of a SARS-like disease caused by Middle East respiratory syndrome coronavirus (MERS-CoV) have raised serious concerns of a possible reemergence of SARS-CoV, either by laboratory escape or the presence of a natural reservoir. Therefore, the development of effective and safe SARS vaccines is still needed. Based on our previous studies, we believe that the receptor-binding domain (RBD) in the S1 subunit of the SARS-CoV spike (S) protein is the most important target for developing a SARS vaccine. In particular, RBD of S protein contains the critical neutralizing domain (CND), which is able to induce highly potent neutralizing antibody response and cross-protection against divergent SARS-CoV strains. Furthermore, a RBD-based subunit vaccine is expected to be safer than other vaccines that may induce Th2-type immunopathology. This review will discuss key advances in the development of RBD-based SARS vaccines and the possibility of using a similar strategy to develop vaccines against MERS-CoV.",,"['Zhu, Xiaojie', 'Liu, Qi', 'Du, Lanying', 'Lu, Lu', 'Jiang, Shibo']",,,,
,PMC,Severe acute respiratory syndrome: a vanished evil?,http://dx.doi.org/10.3978/j.issn.2072-1439.2013.02.08,PMC3747533,,,,,"['Guan, Wei-Jie', 'Zheng, Xue-Yan', 'Zeng, Guang-Qiao', 'Zhong, Nan-Shan']",,,,
,PMC,Professor Stephen Kwok-Wing Tsui: targeting pathogen genomes,http://dx.doi.org/10.3978/j.issn.2072-1439.2013.05.27,PMC3747531,,,,,"Li, Grace",,,,
,PMC,Ten years after SARS: where was the virus from?,http://dx.doi.org/10.3978/j.issn.2072-1439.2013.06.09,PMC3747529,,,,,"['Chen, Feng', 'Cao, Si', 'Xin, Junqing', 'Luo, Xiaohua']",,,,
,PMC,Novel hemagglutinin-based influenza virus inhibitors,http://dx.doi.org/10.3978/j.issn.2072-1439.2013.06.14,PMC3747528,,,"Influenza virus has caused seasonal epidemics and worldwide pandemics, which caused tremendous loss of human lives and socioeconomics. Nowadays, only two classes of anti-influenza drugs, M2 ion channel inhibitors and neuraminidase inhibitors respectively, are used for prophylaxis and treatment of influenza virus infection. Unfortunately, influenza virus strains resistant to one or all of those drugs emerge frequently. Hemagglutinin (HA), the glycoprotein in influenza virus envelope, plays a critical role in viral binding, fusion and entry processes. Therefore, HA is a promising target for developing anti-influenza drugs, which block the initial entry step of viral life cycle. Here we reviewed recent understanding of conformational changes of HA in protein folding and fusion processes, and the discovery of HA-based influenza entry inhibitors, which may provide more choices for preventing and controlling potential pandemics caused by multi-resistant influenza viruses.",,"['Shen, Xintian', 'Zhang, Xuanxuan', 'Liu, Shuwen']",,,,
,PMC,Guideline on prevention and control of H7N9 avian influenza human infection,http://dx.doi.org/10.3978/j.issn.2072-1439.2013.05.17,PMC3747527,,,,,,,,,
,PMC,"Chance missed, but still there! Memoirs at the 10(th) anniversary of 2003 SARS outbreak",http://dx.doi.org/10.3978/j.issn.2072-1439.2013.04.07,PMC3747526,,,,,"Xu, Ruiheng",,,,
,PMC,The war against infectious respiratory disease goes on: report on the 10(th) anniversary symposium of anti-SARS,http://dx.doi.org/10.3978/j.issn.2072-1439.2013.08.05,PMC3747525,,,,,"['He, Melanie C.', 'Li, Grace', 'Zeng, Guang-Qiao']",,,,
,PMC,"Influenza seasonality and predominant subtypes of influenza virus in Guangdong, China, 2004-2012",http://dx.doi.org/10.3978/j.issn.2072-1439.2013.08.09,PMC3747524,,,"BACKGROUND: Influenza surveillance is carried out in Guangdong province, southern China. A better understanding of influenza seasonality and predominant Subtypes of influenza virus in Guangdong can help to improve evidence-based prevention and control strategies for influenza in the future. MATERIALS AND METHODS: There are three categories of influenza surveillance in Guangdong: Influenza-like Illness (ILI) Outpatient Surveillance, ILI Outbreak Surveillance and Influenza Virus Surveillance. This paper summarizes collected influenza surveillance data from January 2004 to December 2012 in Guangdong province. Time series analysis and “peak analysis” were performed to estimate seasonality and temporal trends of influenza activity. RESULTS: During the 9-year study period, a total of 37,571,582 outpatients had been recorded, in which 1,889,684 ILI cases had been reported. The provincial ILI visiting percentage peaked at 6-10%. A total of 107,115 respiratory specimens of ILI outpatients were collected, 17,454 (16.29%) of them tested for influenza virus were positive. Influenza virus peaks appeared in summer mostly with a median epidemic duration of 6 months. A total of 925 outbreaks recorded and 45,322 cases in which were affected. The majority of reported outbreaks (832 outbreaks, 90%) occurred in institutional settings. CONCLUSIONS: Influenza circulates periodically every year in Guangdong. Influenza activity had strong and clear seasonality with epidemic periods in summer for last decade. The presence of local unique seasonal pattern and its changes emphasizes the need to optimize timing of influenza vaccine delivery and other public health interventions.",,"['Lin, Jinyan', 'Kang, Min', 'Zhong, Haojie', 'Zhang, Xin', 'Yang, Fen', 'Ni, Hangzhong', 'Huang, Ping', 'Hong, Teng', 'Ke, Changwen', 'He, Jianfeng']",,,,
,PMC,From SARS coronavirus to novel animal and human coronaviruses,http://dx.doi.org/10.3978/j.issn.2072-1439.2013.06.02,PMC3747523,,,"In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) caused one of the most devastating epidemics known to the developed world. There were two important lessons from this epidemic. Firstly, coronaviruses, in addition to influenza viruses, can cause severe and rapidly spreading human infections. Secondly, bats can serve as the origin and natural animal reservoir of deadly human viruses. Since then, researchers around the world, especially those in Asia where SARS-CoV was first identified, have turned their focus to find novel coronaviruses infecting humans, bats, and other animals. Two human coronaviruses, HCoV-HKU1 and HCoV-NL63, were identified shortly after the SARS-CoV epidemic as common causes of human respiratory tract infections. In 2012, a novel human coronavirus, now called Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in the Middle East to cause fatal human infections in three continents. MERS-CoV human infection is similar to SARS-CoV in having a high fatality rate and the ability to spread from person to person which resulted in secondary cases among close contacts including healthcare workers without travel history to the Middle East. Both viruses also have close relationships with bat coronaviruses. New cases of MERS-CoV infection in humans continue to occur with the origins of the virus still unknown in many cases. A multifaceted approach is necessary to control this evolving MERS-CoV outbreak. Source identification requires detailed epidemiological studies of the infected patients and enhanced surveillance of MERS-CoV or similar coronaviruses in humans and animals. Early diagnosis of infected patients and appropriate infection control measures will limit the spread in hospitals, while social distancing strategies may be necessary to control the outbreak in communities if it remained uncontrolled as in the SARS epidemic.",,"['To, Kelvin K. W.', 'Hung, Ivan F. N.', 'Chan, Jasper F. W.', 'Yuen, Kwok-Yung']",,,,
,PMC,Tracing the SARS-coronavirus,http://dx.doi.org/10.3978/j.issn.2072-1439.2013.06.19,PMC3747522,,,"Four coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1) are endemic in humans and mainly associated with mild respiratory illnesses; whereas the other two coronaviruses [Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV)] present as emerging infections causing severe respiratory syndrome. Coronaviruses evolve by accumulation of point mutations and recombination of genomes among different strains or species. Mammalian coronaviruses including those infect humans are evolved from bat coronaviruses. While SARS-CoV and MERS-CoV are genetically closely related to bat coronaviruses, intermediate host(s) is (are) likely to be involved in the emergence and cross-species transmission of these novel human viruses. High prevalence of SARS-like coronaviruses have been found from masked palm civet cats and raccoon dogs collected from markets around the time of outbreaks in humans, but these animals are likely to be a transient accidental host rather than a persisting reservoir. More research is needed to elucidate the ecology of coronaviruses. Vigilance and surveillance should be maintained to promptly identify newly emerged coronaviruses.",,"['Chan, Paul K. S.', 'Chan, Martin C. W.']",,,,
,PMC,Severe acute respiratory syndrome (SARS): lessons learnt in Hong Kong,http://dx.doi.org/10.3978/j.issn.2072-1439.2013.06.18,PMC3747521,,,"Many healthcare workers were infected while looking after the SARS patients on the medical wards in 2003. The high infectivity of the SARS coronavirus with peak viral load on day 10 of illness when patients were ill, overcrowding of the old medical wards with low air changes/hr (ACH), and aerosol-generating procedures while resuscitating the patients were the major factors. Procedures reported to present an increased risk of SARS transmission include tracheal intubation, non-invasive ventilation, tracheotomy and manual ventilation before intubation whereas oxygen therapy and bed distance <1 m were also implicated. Studies based on laser visualization technique with smoke particles as smokers in the human patient simulator has shown that oxygen therapy via Hudson mask and nasal cannula could disperse exhaled air of patients to 0.4 and 1 m respectively whereas jet nebulizer could disperse exhaled air >0.8 m from the patient. Bigger isolation rooms with 16 ACH are more effective than smaller isolation rooms with 12 ACH in removing exhaled air and preventing room contamination but at the expense of more noise and electricity consumption. Non-invasive ventilation via face masks and single circuit can disperse exhaled air from 0.4 to 1 m. Both higher inspiratory pressures and use of whisper swivel device (to facilitate carbon dioxide removal) could increase the exhaled air leakage and isolation room contamination during on-invasive ventilation. Addition of a viral-bacterial filter during manual ventilation by bagging may reduce the exhaled air leakage forward and yet increase the sideway leakage. N95 mask was more effective than surgical mask in preventing expelled air leakage during patient’s coughing but there was still significant sideway leakage to 15 cm. Clinicians should be aware of air leakage from the various face masks and adopt strict infection control measures during resuscitation of patients with severe respiratory infections. Carefully designed clinical trials are required to determine the optimal timing and dosage of any antiviral agents, convalescent plasma, and immuno-modulating agents in the treatment of the possibly immune-mediated lung injury in SARS and newly emerged infection such as the Middle East Respiratory Syndrome.",,"Hui, David S.",,,,
,PMC,Mutations in the Capsid Protein of Brome Mosaic Virus Affecting Encapsidation Eliminate Vesicle Induction In Planta: Implications for Virus Cell-to-Cell Spread,http://dx.doi.org/10.1128/JVI.01253-13,PMC3754083,,,"Positive-strand RNA viruses are known to rearrange the endomembrane network to make it more conducive for replication, maturation, or egress. Our previous transmission electron microscopic (TEM) analysis showed that ectopic expression of wild-type (wt) capsid protein (CP) of Brome mosaic virus (BMV) has an intrinsic property of modifying the endoplasmic reticulum (ER) to induce vesicles similar to those present in wt BMV infection. In this study, we evaluated the functional significance of CP-mediated vesicle induction to the BMV infection cycle in planta. Consequently, the cytopathologic changes induced by wt CP or its mutants defective in virion assembly due to mutations engineered in either N- or C-proximal domains were comparatively analyzed by TEM in two susceptible (Nicotiana benthamiana and Chenopodium quinoa) and one nonhost (N. clevelandii) plant species. The results showed that in susceptible hosts, CP-mediated ER-derived vesicle induction is contingent on the expression of encapsidation-competent CP. In contrast, unlike in N. benthamiana and C. quinoa, transient expression of wt CP in nonhost N. clevelandii plants eliminated vesicle induction. Additionally, comparative source-to-sink analysis of virus spread in leaves of N. benthamiana and N. clevelandii coexpressing wt BMV and Cucumber mosaic virus (CMV) showed that despite trans-encapsidation, CMV failed to complement the defective cell-to-cell movement of BMV. The significance and relation of CP-mediated vesicle induction to virus cell-to-cell movement are discussed.",,"['Bamunusinghe, Devinka', 'Chaturvedi, Sonali', 'Seo, Jang-Kyun', 'Rao, A. L. N.']",,,,
,PMC,Characterization of a Critical Interaction between the Coronavirus Nucleocapsid Protein and Nonstructural Protein 3 of the Viral Replicase-Transcriptase Complex,http://dx.doi.org/10.1128/JVI.01275-13,PMC3754073,,,"The coronavirus nucleocapsid protein (N) plays an essential structural role in virions through a network of interactions with positive-strand viral genomic RNA, the envelope membrane protein (M), and other N molecules. Additionally, N protein participates in at least one stage of the complex mechanism of coronavirus RNA synthesis. We previously uncovered an unanticipated interaction between N and the largest subunit of the viral replicase-transcriptase complex, nonstructural protein 3 (nsp3). This was found through analysis of revertants of a severely defective mutant of murine hepatitis virus (MHV) in which the N gene was replaced with that of its close relative, bovine coronavirus (BCoV). In the work reported here, we constructed BCoV chimeras and other mutants of MHV nsp3 and obtained complementary genetic evidence for its association with N protein. We found that the N-nsp3 interaction maps to the amino-terminal ubiquitin-like domain of nsp3, which is essential for the virus. The interaction does not require the adjacent acidic domain of nsp3, which is dispensable. In addition, we demonstrated a complete correspondence between N-nsp3 genetic interactions and the ability of N protein to enhance the infectivity of transfected coronavirus genomic RNA. The latter function of N was shown to depend on both of the RNA-binding domains of N, as well as on the serine- and arginine-rich central region of N, which binds nsp3. Our results support a model in which the N-nsp3 interaction serves to tether the genome to the newly translated replicase-transcriptase complex at a very early stage of infection.",,"['Hurst, Kelley R.', 'Koetzner, Cheri A.', 'Masters, Paul S.']",,,,
,PMC,The Receptor Binding Domain of the New Middle East Respiratory Syndrome Coronavirus Maps to a 231-Residue Region in the Spike Protein That Efficiently Elicits Neutralizing Antibodies,http://dx.doi.org/10.1128/JVI.01277-13,PMC3754068,,,The spike (S) protein of the recently emerged human Middle East respiratory syndrome coronavirus (MERS-CoV) mediates infection by binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). Here we mapped the receptor binding domain in the S protein to a 231-amino-acid fragment (residues 358 to 588) by evaluating the interaction of spike truncation variants with receptor-expressing cells and soluble DPP4. Antibodies to this domain—much less so those to the preceding N-terminal region—efficiently neutralize MERS-CoV infection.,,"['Mou, Huihui', 'Raj, V. Stalin', 'van Kuppeveld, Frank J. M.', 'Rottier, Peter J. M.', 'Haagmans, Bart L.', 'Bosch, Berend Jan']",,,,
,PMC,Role of RNA Interference (RNAi) in Dengue Virus Replication and Identification of NS4B as an RNAi Suppressor,http://dx.doi.org/10.1128/JVI.02774-12,PMC3754049,,,"RNA interference (RNAi) is an important antiviral defense response in plants and invertebrates; however, evidences for its contribution to mammalian antiviral defense are few. In the present study, we demonstrate the anti-dengue virus role of RNAi in mammalian cells. Dengue virus infection of Huh 7 cells decreased the mRNA levels of host RNAi factors, namely, Dicer, Drosha, Ago1, and Ago2, and in corollary, silencing of these genes in virus-infected cells enhanced dengue virus replication. In addition, we observed downregulation of many known human microRNAs (miRNAs) in response to viral infection. Using reversion-of-silencing assays, we further showed that NS4B of all four dengue virus serotypes is a potent RNAi suppressor. We generated a series of deletion mutants and demonstrated that NS4B mediates RNAi suppression via its middle and C-terminal domains, namely, transmembrane domain 3 (TMD3) and TMD5. Importantly, the NS4B N-terminal region, including the signal sequence 2K, which has been implicated in interferon (IFN)-antagonistic properties, was not involved in mediating RNAi suppressor activity. Site-directed mutagenesis of conserved residues revealed that a Phe-to-Ala (F112A) mutation in the TMD3 region resulted in a significant reduction of the RNAi suppression activity. The green fluorescent protein (GFP)-small interfering RNA (siRNA) biogenesis of the GFP-silenced line was considerably reduced by wild-type NS4B, while the F112A mutant abrogated this reduction. These results were further confirmed by in vitro dicer assays. Together, our results suggest the involvement of miRNA/RNAi pathways in dengue virus establishment and that dengue virus NS4B protein plays an important role in the modulation of the host RNAi/miRNA pathway to favor dengue virus replication.",,"['Kakumani, Pavan Kumar', 'Ponia, Sanket Singh', 'S, Rajgokul K.', 'Sood, Vikas', 'Chinnappan, Mahendran', 'Banerjea, Akhil C.', 'Medigeshi, Guruprasad R.', 'Malhotra, Pawan', 'Mukherjee, Sunil K.', 'Bhatnagar, Raj K.']",,,,
,PMC,A Cholesterol Tag at the N Terminus of the Relatively Broad-Spectrum Fusion Inhibitory Peptide Targets an Earlier Stage of Fusion Glycoprotein Activation and Increases the Peptide's Antiviral Potency In Vivo,http://dx.doi.org/10.1128/JVI.01153-13,PMC3754040,,,"In previous work, we designed peptides that showed potent inhibition of Newcastle disease virus (NDV) and infectious bronchitis virus (IBV) infections in chicken embryos. In this study, we demonstrate that peptides modified with cholesterol or 3 U of polyethylene glycol (PEG(3)) conjugated to the peptides' N termini showed even more promising antiviral activities when tested in animal models. Both cholesterol- and cholesterol-PEG(3)-tagged peptides were able to protect chicken embryos from infection with different serotypes of NDV and IBV when administered 12 h prior to virus inoculation. In comparison, the untagged peptides required intervention closer to the time of viral inoculation to achieve a similar level of protection. Intramuscular injection of cholesterol-tagged peptide at 1.6 mg/kg 1 day before virus infection and then three times at 3-day intervals after viral inoculation protected 70% of the chickens from NDV infection. We further demonstrate that the cholesterol-tagged peptide has an in vivo half-life greater than that of untagged peptides. It also has the potential to cross the blood-brain barrier to enter the avian central nervous system (CNS). Finally, we show that the cholesterol-tagged peptide could play a role before the viral fusion peptide's insertion into the host cell and thereby target an earlier stage of fusion glycoprotein activation. Our findings are of importance for the further development of antivirals with broad-spectrum protective effects.",,"['Li, Chuan-Gen', 'Tang, Wang', 'Chi, Xiao-Jing', 'Dong, Zhi-Ming', 'Wang, Xi-Xi', 'Wang, Xiao-Jia']",,,,
,PMC,The Endosomal Pathway and the Golgi Complex Are Involved in the Infectious Bursal Disease Virus Life Cycle,http://dx.doi.org/10.1128/JVI.03152-12,PMC3754037,,,"Infectious bursal disease virus (IBDV), a double-stranded RNA virus belonging to the Birnaviridae family, causes immunosuppression in chickens. In this study, we defined the localization of IBDV replication complexes based on colocalization analysis of VP3, the major protein component of IBDV ribonucleoproteins (RNPs). Our results indicate that VP3 localizes to vesicular structures bearing features of early and late endocytic compartments located in the juxtanuclear region. Interfering with the endocytic pathway with a dominant negative version of Rab5 after the internalization step leads to a reduction in virus titer. Triple-immunostaining studies between VP3, the viral RNA-dependent RNA polymerase VP1, and viral double-stranded RNA (dsRNA) showed a well-defined colocalization, indicating that the three critical components of the RNPs colocalize in the same structure, likely representing replication complexes. Interestingly, recombinant expressed VP3 also localizes to endosomes. Employing Golgi markers, we found that VP3-containing vesicles were closely associated with this organelle. Depolymerization of microtubules with nocodazole caused a profound change in VP3 localization, showing a punctate distribution scattered throughout the cytoplasm. However, these VP3-positive structures remained associated with Golgi ministacks. Similarly, brefeldin A (BFA) treatment led to a punctate distribution of VP3, scattered throughout the cytoplasm of infected cells. In addition, analysis of intra- and extracellular viral infective particles after BFA treatment of avian cells suggested a role for the Golgi complex in viral assembly. These results constitute the first study elucidating the localization of IBDV replication complexes (i.e., in endocytic compartments) and establishing a role for the Golgi apparatus in the assembly step of a birnavirus.",,"['Delgui, Laura R.', 'Rodríguez, José F.', 'Colombo, María I.']",,,,
,PMC,Caveolar Endocytosis Is Required for Human PSGL-1-Mediated Enterovirus 71 Infection,http://dx.doi.org/10.1128/JVI.00573-13,PMC3754029,,,"Enterovirus 71 (EV71) causes hand, foot, and mouth disease and severe neurological disorders in children. Human scavenger receptor class B member 2 (hSCARB2) and P-selectin glycoprotein ligand-1 (PSGL-1) are identified as receptors for EV71. The underling mechanism of PSGL-1-mediated EV71 entry remains unclear. The endocytosis required for EV71 entry were investigated in Jurkat T and mouse L929 cells constitutively expressing human PSGL-1 (PSGL-1-L929) or human rhabdomyosarcoma (RD) cells displaying high SCARB2 but no PSGL-1 by treatment of specific inhibitors or siRNA. We found that disruption of clathrin-dependent endocytosis prevented EV71 infection in RD cells, while there was no influence in Jurkat T and PSGL-1-L929 cells. Disturbing caveolar endocytosis by specific inhibitor or caveolin-1 siRNA in Jurkat T and PSGL-1-L929 cells significantly blocked EV71 infection, whereas it had no effect on EV71 infection in RD cells. Confocal immunofluorescence demonstrated caveola, and EV71 was directly colocalized. pH-dependent endosomal acidification and intact membrane cholesterol were important for EV71 infection, as judged by the pretreatment of inhibitors that abrogated the infection. A receptor-dominated endocytosis of EV71 infection was observed: PSGL-1 initiates caveola-dependent endocytosis and hSCARB2 activates clathrin-dependent endocytosis.",,"['Lin, Hsiang-Yin', 'Yang, Ya-Ting', 'Yu, Shu-Ling', 'Hsiao, Kuang-Nan', 'Liu, Chia-Chyi', 'Sia, Charles', 'Chow, Yen-Hung']",,,,
,PMC,Genome-Wide Characterization of Endogenous Retroviruses in the Bat Myotis lucifugus Reveals Recent and Diverse Infections,http://dx.doi.org/10.1128/JVI.00892-13,PMC3719839,,,"Bats are increasingly recognized as reservoir species for a variety of zoonotic viruses that pose severe threats to human health. While many RNA viruses have been identified in bats, little is known about bat retroviruses. Endogenous retroviruses (ERVs) represent genomic fossils of past retroviral infections and, thus, can inform us on the diversity and history of retroviruses that have infected a species lineage. Here, we took advantage of the availability of a high-quality genome assembly for the little brown bat, Myotis lucifugus, to systematically identify and analyze ERVs in this species. We mined an initial set of 362 potentially complete proviruses from the three main classes of ERVs, which were further resolved into 13 major families and 86 subfamilies by phylogenetic analysis. Consensus or representative sequences for each of the 86 subfamilies were then merged to the Repbase collection of known ERV/long terminal repeat (LTR) elements to annotate the retroviral complement of the bat genome. The results show that nearly 5% of the genome assembly is occupied by ERV-derived sequences, a quantity comparable to findings for other eutherian mammals. About one-fourth of these sequences belong to subfamilies newly identified in this study. Using two independent methods, intraelement LTR divergence and analysis of orthologous loci in two other bat species, we found that the vast majority of the potentially complete proviruses identified in M. lucifugus were integrated in the last ∼25 million years. All three major ERV classes include recently integrated proviruses, suggesting that a wide diversity of retroviruses is still circulating in Myotis bats.",,"['Zhuo, Xiaoyu', 'Rho, Mina', 'Feschotte, Cédric']",,,,
,PMC,In Vivo Bioluminescent Imaging of Influenza A Virus Infection and Characterization of Novel Cross-Protective Monoclonal Antibodies,http://dx.doi.org/10.1128/JVI.00969-13,PMC3719835,,,"Influenza A virus is a major human pathogen responsible for seasonal epidemics as well as pandemic outbreaks. Due to the continuing burden on human health, the need for new tools to study influenza virus pathogenesis as well as to evaluate new therapeutics is paramount. We report the development of a stable, replication-competent luciferase reporter influenza A virus that can be used for in vivo imaging of viral replication. This imaging is noninvasive and allows for the longitudinal monitoring of infection in living animals. We used this tool to characterize novel monoclonal antibodies that bind the conserved stalk domain of the viral hemagglutinin of H1 and H5 subtypes and protect mice from lethal disease. The use of luciferase reporter influenza viruses allows for new mechanistic studies to expand our knowledge of virus-induced disease and provides a new quantitative method to evaluate future antiviral therapies.",,"['Heaton, Nicholas S.', 'Leyva-Grado, Victor H.', 'Tan, Gene S.', 'Eggink, Dirk', 'Hai, Rong', 'Palese, Peter']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.01531-13,PMC3719832,,,,,,,,,
,PMC,Role of the Phosphatidylserine Receptor TIM-1 in Enveloped-Virus Entry,http://dx.doi.org/10.1128/JVI.01025-13,PMC3719829,,,"The cell surface receptor T cell immunoglobulin mucin domain 1 (TIM-1) dramatically enhances filovirus infection of epithelial cells. Here, we showed that key phosphatidylserine (PtdSer) binding residues of the TIM-1 IgV domain are critical for Ebola virus (EBOV) entry through direct interaction with PtdSer on the viral envelope. PtdSer liposomes but not phosphatidylcholine liposomes competed with TIM-1 for EBOV pseudovirion binding and transduction. Further, annexin V (AnxV) substituted for the TIM-1 IgV domain, supporting a PtdSer-dependent mechanism. Our findings suggest that TIM-1-dependent uptake of EBOV occurs by apoptotic mimicry. Additionally, TIM-1 enhanced infection of a wide range of enveloped viruses, including alphaviruses and a baculovirus. As further evidence of the critical role of enveloped-virion-associated PtdSer in TIM-1-mediated uptake, TIM-1 enhanced internalization of pseudovirions and virus-like proteins (VLPs) lacking a glycoprotein, providing evidence that TIM-1 and PtdSer-binding receptors can mediate virus uptake independent of a glycoprotein. These results provide evidence for a broad role of TIM-1 as a PtdSer-binding receptor that mediates enveloped-virus uptake. Utilization of PtdSer-binding receptors may explain the wide tropism of many of these viruses and provide new avenues for controlling their virulence.",,"['Moller-Tank, Sven', 'Kondratowicz, Andrew S.', 'Davey, Robert A.', 'Rennert, Paul D.', 'Maury, Wendy']",,,,
,PMC,Cell-Type-Specific Activation of the Oligoadenylate Synthetase–RNase L Pathway by a Murine Coronavirus,http://dx.doi.org/10.1128/JVI.00769-13,PMC3719824,,,"Previous studies have demonstrated that the murine coronavirus mouse hepatitis virus (MHV) nonstructural protein 2 (ns2) is a 2′,5′-phosphodiesterase that inhibits activation of the interferon-induced oligoadenylate synthetase (OAS)-RNase L pathway. Enzymatically active ns2 is required for efficient MHV replication in macrophages, as well as for the induction of hepatitis in C57BL/6 mice. In contrast, following intranasal or intracranial inoculation, efficient replication of MHV in the brain is not dependent on an enzymatically active ns2. The replication of wild-type MHV strain A59 (A59) and a mutant with an inactive phosphodiesterase (ns2-H126R) was assessed in primary hepatocytes and primary central nervous system (CNS) cell types—neurons, astrocytes, and oligodendrocytes. A59 and ns2-H126R replicated with similar kinetics in all cell types tested, except macrophages and microglia. RNase L activity, as assessed by rRNA cleavage, was induced by ns2-H126R, but not by A59, and only in macrophages and microglia. Activation of RNase L correlated with the induction of type I interferon and the consequent high levels of OAS mRNA induced in these cell types. Pretreatment of nonmyeloid cells with interferon restricted A59 and ns2-H126R to the same extent and failed to activate RNase L following infection, despite induction of OAS expression. However, rRNA degradation was induced by treatment of astrocytes or oligodendrocytes with poly(I·C). Thus, RNase L activation during MHV infection is cell type specific and correlates with relatively high levels of expression of OAS genes, which are necessary but not sufficient for induction of an effective RNase L antiviral response.",,"['Zhao, Ling', 'Birdwell, L. Dillon', 'Wu, Ashley', 'Elliott, Ruth', 'Rose, Kristine M.', 'Phillips, Judith M.', 'Li, Yize', 'Grinspan, Judith', 'Silverman, Robert H.', 'Weiss, Susan R.']",,,,
,PMC,Genetic Characterization of Betacoronavirus Lineage C Viruses in Bats Reveals Marked Sequence Divergence in the Spike Protein of Pipistrellus Bat Coronavirus HKU5 in Japanese Pipistrelle: Implications for the Origin of the Novel Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.01055-13,PMC3719811,,,"While the novel Middle East respiratory syndrome coronavirus (MERS-CoV) is closely related to Tylonycteris bat CoV HKU4 (Ty-BatCoV HKU4) and Pipistrellus bat CoV HKU5 (Pi-BatCoV HKU5) in bats from Hong Kong, and other potential lineage C betacoronaviruses in bats from Africa, Europe, and America, its animal origin remains obscure. To better understand the role of bats in its origin, we examined the molecular epidemiology and evolution of lineage C betacoronaviruses among bats. Ty-BatCoV HKU4 and Pi-BatCoV HKU5 were detected in 29% and 25% of alimentary samples from lesser bamboo bat (Tylonycteris pachypus) and Japanese pipistrelle (Pipistrellus abramus), respectively. Sequencing of their RNA polymerase (RdRp), spike (S), and nucleocapsid (N) genes revealed that MERS-CoV is more closely related to Pi-BatCoV HKU5 in RdRp (92.1% to 92.3% amino acid [aa] identity) but is more closely related to Ty-BatCoV HKU4 in S (66.8% to 67.4% aa identity) and N (71.9% to 72.3% aa identity). Although both viruses were under purifying selection, the S of Pi-BatCoV HKU5 displayed marked sequence polymorphisms and more positively selected sites than that of Ty-BatCoV HKU4, suggesting that Pi-BatCoV HKU5 may generate variants to occupy new ecological niches along with its host in diverse habitats. Molecular clock analysis showed that they diverged from a common ancestor with MERS-CoV at least several centuries ago. Although MERS-CoV may have diverged from potential lineage C betacoronaviruses in European bats more recently, these bat viruses were unlikely to be the direct ancestor of MERS-CoV. Intensive surveillance for lineage C betaCoVs in Pipistrellus and related bats with diverse habitats and other animals in the Middle East may fill the evolutionary gap.",,"['Lau, Susanna K. P.', 'Li, Kenneth S. M.', 'Tsang, Alan K. L.', 'Lam, Carol S. F.', 'Ahmed, Shakeel', 'Chen, Honglin', 'Chan, Kwok-Hung', 'Woo, Patrick C. Y.', 'Yuen, Kwok-Yung']",,,,
,PMC,"Pyrrolidine Dithiocarbamate Inhibits Herpes Simplex Virus 1 and 2 Replication, and Its Activity May Be Mediated through Dysregulation of the Ubiquitin-Proteasome System",http://dx.doi.org/10.1128/JVI.00869-13,PMC3719803,,,"Pyrrolidine dithiocarbamate (PDTC) is widely used as an antioxidant or an NF-κB inhibitor. It has been reported to inhibit the replication of human rhinoviruses, poliovirus, coxsackievirus, and influenza virus. In this paper, we report that PDTC could inhibit the replication of herpes simplex virus 1 and 2 (HSV-1 and HSV-2). PDTC suppressed the expression of HSV-1 and HSV-2 viral immediate early (IE) and late (membrane protein gD) genes and the production of viral progeny. This antiviral property was mediated by the dithiocarbamate moiety of PDTC and required the presence of Zn(2+). Although PDTC could potently block reactive oxygen species (ROS) generation, it was found that this property did not contribute to its anti-HSV activity. PDTC showed no activity in disrupting the mitogen-activated protein kinase (MAPK) pathway activation induced by viral infection that was vital for the virus's propagation. We found that PDTC modulated cellular ubiquitination and, furthermore, influenced HSV-2-induced IκB-α degradation to inhibit NF-κB activation and enhanced PML stability in the nucleus, resulting in the inhibition of viral gene expression. These results suggested that the antiviral activity of PDTC might be mediated by its dysregulation of the cellular ubiquitin-proteasome system (UPS).",,"['Qiu, Min', 'Chen, Yu', 'Cheng, Lin', 'Chu, Ying', 'Song, Hong-Yong', 'Wu, Zhi-Wei']",,,,
,PMC,Thiouracil Cross-Linking Mass Spectrometry: a Cell-Based Method To Identify Host Factors Involved in Viral Amplification,http://dx.doi.org/10.1128/JVI.00950-13,PMC3719794,,,"Eukaryotic RNA viruses are known to utilize host factors; however, the identity of these factors and their role in the virus life cycle remain largely undefined. Here, we report a method to identify proteins bound to the viral RNA during amplification in cell culture: thiouracil cross-linking mass spectrometry (TUX-MS). TUX-MS relies on incorporation of a zero-distance cross-linker into the viral RNA during infection. Proteins bound to viral RNA are cross-linked prior to cell lysis, purified, and identified using mass spectrometry. Using the TUX-MS method, an unbiased screen for poliovirus (PV) host factors was conducted. All host and viral proteins that are known to interact with the poliovirus RNA were identified. In addition, TUX-MS identified an additional 66 host proteins that have not been previously described in poliovirus amplification. From these candidates, eight were selected and validated. Furthermore, we demonstrate that small interfering RNA (siRNA)-mediated knockdown of two of these uncharacterized host factors results in either a decrease in copy number of positive-stranded RNA or a decrease in PV translation. These data demonstrate that TUX-MS is a robust, unbiased method to identify previously unknown host cell factors that influence virus growth. This method is broadly applicable to a range of RNA viruses, such as flaviviruses, alphaviruses, picornaviruses, bunyaviruses, and coronaviruses.",,"['Lenarcic, Erik M.', 'Landry, Dori M.', 'Greco, Todd M.', 'Cristea, Ileana M.', 'Thompson, Sunnie R.']",,,,
,PMC,IFITM-2 and IFITM-3 but Not IFITM-1 Restrict Rift Valley Fever Virus,http://dx.doi.org/10.1128/JVI.03382-12,PMC3719792,,,"We show that interferon-induced transmembrane protein 1 (IFITM-1), IFITM-2, and IFITM-3 exhibit a broad spectrum of antiviral activity against several members of the Bunyaviridae family, including Rift Valley fever virus (RVFV), La Crosse virus, Andes virus, and Hantaan virus, all of which can cause severe disease in humans and animals. We found that RVFV was restricted by IFITM-2 and -3 but not by IFITM-1, whereas the remaining viruses were equally restricted by all IFITMs. Indeed, at low doses of alpha interferon (IFN-α), IFITM-2 and -3 mediated more than half of the antiviral activity of IFN-α against RVFV. IFITM-2 and -3 restricted RVFV infection mostly by preventing virus membrane fusion with endosomes, while they had no effect on virion attachment to cells, endocytosis, or viral replication kinetics. We found that large fractions of IFITM-2 and IFITM-3 occupy vesicular compartments that are distinct from the vesicles coated by IFITM-1. In addition, although overexpression of all IFITMs expanded vesicular and acidified compartments within cells, there were marked phenotypic differences among the vesicular compartments occupied by IFITMs. Collectively, our data provide new insights into the possible mechanisms by which the IFITM family members restrict distinct viruses.",,"['Mudhasani, Rajini', 'Tran, Julie P.', 'Retterer, Cary', 'Radoshitzky, Sheli R.', 'Kota, Krishna P.', 'Altamura, Louis A.', 'Smith, Jeffrey M.', 'Packard, Beverly Z.', 'Kuhn, Jens H.', 'Costantino, Julie', 'Garrison, Aura R.', 'Schmaljohn, Connie S.', 'Huang, I-Chueh', 'Farzan, Michael', 'Bavari, Sina']",,,,
,PMC,The replication of a mouse adapted SARS-CoV in a mouse cell line stably expressing the murine SARS-CoV receptor mACE2 efficiently induces the expression of proinflammatory cytokines,http://dx.doi.org/10.1016/j.jviromet.2013.07.039,PMC3805046,,,"Infection of conventional mice with a mouse adapted (MA15) severe acute respiratory syndrome (SARS) coronavirus (CoV) reproduces many aspects of human SARS such as pathological changes in lung, viremia, neutrophilia, and lethality. However, established mouse cell lines highly susceptible to mouse-adapted SARS-CoV infection are not available. In this work, efficiently transfectable mouse cell lines stably expressing the murine SARS-CoV receptor angiotensin converting enzyme 2 (ACE2) have been generated. These cells yielded high SARS-CoV-MA15 titers and also served as excellent tools for plaque assays. In addition, in these cell lines, SARS-CoV-MA15 induced the expression of proinflammatory cytokines and IFN-β, mimicking what has been observed in experimental animal models infected with SARS-CoV and SARS patients. These cell lines are valuable tools to perform in vitro studies in a mouse cell system that reflects the species used for in vivo studies of SARS-CoV-MA15 pathogenesis.",,"['Regla-Nava, Jose A.', 'Jimenez-Guardeño, Jose M.', 'Nieto-Torres, Jose L.', 'Gallagher, Thomas M.', 'Enjuanes, Luis', 'DeDiego, Marta L.']",,,,
,PMC,Fully Phosphorothioate-Modified CpG ODN with PolyG Motif Inhibits the Adhesion of B16 Melanoma Cells In Vitro and Tumorigenesis In Vivo,http://dx.doi.org/10.1089/nat.2013.0419,PMC3723239,,,"Adhesion to the extracellular matrix and endothelial lining of blood vessels is critical for tumor cells to grow at original or metastatic sites. Inhibition of tumor cell adhesion can be an antitumor strategy. Guanosine-rich (G-rich) oligodeoxynucleotides (ODNs) can inhibit the adhesion of certain tumor cells. However, no data exist on how inclusion of the CpG motif in the G-rich sequence influences tumor cell adhesion and subsequent tumorigenesis. In this study, in vitro and in vivo assays were used to evaluate how a panel of ODN-containing contiguous guanosines and the CpG motif influenced adhesion of B16 melanoma cells. The results showed that a self-designed ODN, named BW001, containing the polyG motif and a full phosphorothioate modification backbone could inhibit B16 melanoma cell adhesion on a culture plate or on a plate coated with various substances. In vivo data revealed that B16 melanoma cells co-administered with BW001 and intraperitoneally injected into mice formed fewer tumor colonies in peritoneal cavities. This effect was related to the polyG motif and the full phosphorothioate modification backbone and enhanced by the existence of the CpG motif. Additional in vivo data showed that survival of tumor-bearing mice in the BW001 group was significantly prolonged, subcutaneous melanoma developed much more slowly, and lung dissemination colonies formed much less often than in mice inoculated with B16 melanoma cells only. The effect was CpG motif-dependent. These results suggest that BW001 may exert an integrated antitumor effect.",,"['Wang, Xueju', 'Wang, Liying', 'Wan, Min', 'Wu, Xiuli', 'Yu, Yongli', 'Wang, Liping']",,,,
,PMC,Down-regulation of Myelin Gene Expression in Human Oligodendrocytes by Nitric Oxide: Implications for Demyelination in Multiple Sclerosis,http://dx.doi.org/10.4172/2155-9899.1000157,PMC3837467,,,"Multiple sclerosis (MS) is a chronic autoimmune demyelinating disorder of the central nervous system (CNS) with unknown etiology. Several studies have shown that demyelination in MS is caused by proinflammatory mediators and nitric oxide (NO), which is released by perivascular infiltrates and/or activated glial cells. Both endogenous NO released by microglia and astrocytes; and NO generated from exogenous NO donors are known to induce oligodendrocytes death. However, the molecular mechanism of oligodendroglial death is poorly understood. Here we explore the role of NO in modulating the expression of myelin-specific genes that leads to oligodendroglial death. We investigated the effect of NO on the expression of myelin basic protein (MBP), 2’,3’-cyclic nucleotide 3’-phosphodiesterase (CNPase), myelin oligodendrocyte glycoprotein (MOG), and proteolipid protein (PLP) in human primary oligodendrocytes. Combination of IFN-γ and bacterial lipopolysaccharide (LPS) or double stranded RNA in the form of polyIC induced the production of NO and decreased the expression of myelin gene in human fetal mixed glial cultures. Either a scavenger of NO (PTIO) or an inhibitor of inducible nitric oxide synthase (L-NIL) abrogated (LPS+IFN-γ)- and polyIC-mediated suppression of myelin genes in human mixed glial cells. The role of NO was further corroborated by the inhibition of myelin gene expression in purified human oligodendroglia by several NO donors including SNP, NOC-7, SIN-1, and SNAP. This study illustrates a novel biological role of NO in down-regulating the expression of myelin genes preceding the death of oligodendrocytes.",,"['Jana, Malabendu', 'Pahan, Kalipada']",,,,
,PMC,Extending SemRep to the Public Health Domain,http://dx.doi.org/10.1002/asi.22899,PMC3981099,,,"We describe the use of a domain-independent methodology to extend a natural language processing (NLP) application, SemRep (Rindflesch, Fiszman, & Libbus, 2005), based on the knowledge sources afforded by the Unified Medical Language System (UMLS®) (Humphreys, Lindberg, Schoolman, & Barnett, 1998) to support the area of health promotion within the public health domain. Public health professionals require good information about successful health promotion policies and programs that might be considered for application within their own communities. Our effort seeks to improve access to relevant information for the public health profession, to help those in the field remain an information-savvy workforce. NLP and semantic techniques hold promise to help public health professionals navigate the growing ocean of information by organizing and structuring this knowledge into a focused public health framework paired with a user-friendly visualization application as a way to summarize results of PubMed searches in this field of knowledge.",,"['Rosemblat, Graciela', 'Resnick, Melissa P.', 'Auston, Ione', 'Shin, Dongwook', 'Sneiderman, Charles', 'Fizsman, Marcelo', 'Rindflesch, Thomas C.']",,,,
,PMC,Angiotensin converting enzyme 2: A new important player in the regulation of glycemia,http://dx.doi.org/10.1002/iub.1190,PMC4557790,,,"In spite of the novel anti-diabetic drugs available on the market, type 2 diabetes mellitus (T2DM) affects nearly 25 million people in the USA and causes about 5% of all deaths globally each year. Given the rate and proportion by which T2DM is affecting human beings, it is indispensable to identify new therapeutic targets that can control the disease. Recent pre-clinical and clinical studies suggest that attenuating the activity of the renin-angiotensin system (RAS) could improve glycemia in diabetic patients. Angiotensin converting enzyme 2 (ACE2) counteracts RAS over-activity by degrading Ang-II, a vasoconstrictor, to Ang-(1-7) which is a vasodilator. A decrease in ACE2 and an increase in ADAM17-mediated shedding activity have been observed with the progression of T2DM suggesting the importance of this mechanism in the disease. Indeed, restoration of ACE2 improves glycemia in db/db and Ang-II-infused mice. The beneficial effects of ACE2 can be attributed to reduced oxidative stress and ADAM17 expression in the islets of Langerhans in addition to the improvement of blood flow to the β-cells. The advantage of ACE2 over other RAS blockers is that ACE2 not only counteracts the negative effects of Ang-II but also increases Ang-(1-7)/MasR [a receptor through which Ang-(1-7) produces its actions] signaling in the cells. Increased Ang-(1-7)/MasR signaling has been reported to improve insulin sensitivity and glycemia in diabetic animals. Altogether, ACE2/Ang-(1-7)/MasR axis of the RAS appears to be protective in T2DM and strategies to restore ACE2 levels in the disease seem to be a promising therapy for Ang-II-mediated T2DM.",,"['Chhabra, Kavaljit H.', 'Chodavarapu, Harshita', 'Lazartigues, Eric']",,,,
,PMC,Transcriptomic Profiling in Childhood H1N1/09 Influenza Reveals Reduced Expression of Protein Synthesis Genes,http://dx.doi.org/10.1093/infdis/jit348,PMC3805235,,,"We compared the blood RNA transcriptome of children hospitalized with influenza A H1N1/09, respiratory syncytial virus (RSV) or bacterial infection, and healthy controls. Compared to controls, H1N1/09 patients showed increased expression of inflammatory pathway genes and reduced expression of adaptive immune pathway genes. This was validated on an independent cohort. The most significant function distinguishing H1N1/09 patients from controls was protein synthesis, with reduced gene expression. Reduced expression of protein synthesis genes also characterized the H1N1/09 expression profile compared to children with RSV and bacterial infection, suggesting that this is a key component of the pathophysiological response in children hospitalized with H1N1/09 infection.",,"['Herberg, Jethro A.', 'Kaforou, Myrsini', 'Gormley, Stuart', 'Sumner, Edward R.', 'Patel, Sanjay', 'Jones, Kelsey D. J.', 'Paulus, Stéphane', 'Fink, Colin', 'Martinon-Torres, Federico', 'Montana, Giovanni', 'Wright, Victoria J.', 'Levin, Michael']",,,,
,PMC,Rapid detection of human rotavirus using NSP4 gene specific reverse transcription loop-mediated isothermal amplification assay,http://dx.doi.org/10.1007/s13337-013-0147-y,PMC3784908,,,"The seasonal outbreaks of human rotavirus (RV) infection occur every winter. Most patients are diagnosed clinically by a rapid latex agglutination detection kit or polymerase chain reaction assays for RV from stool samples, but some problems have been reported on the specificity and sensitivity of such rapid detection assays. To ratify these issues, a sensitive, specific, simple, and rapid nucleic acid based diagnostic method is expected to be introduced and the reverse transcription loop-mediated isothermal amplification (RT-LAMP) was developed to detect the RV in human stool samples by incubation at 60 °C for 1 h and amplification was confirmed by electrophoretic laddering, restriction enzyme digestion, and hydroxynapthol blue discoloration. The assay established in this study was found to detect only the RVs and no cross-reaction with other viruses, demonstrating its high specificity. By using serial samples dilution as template, the detection limit of LAMP was 10 times more than that of PCR. The results showed the potential clinical feasibility of RT-LAMP as a useful diagnostic tool for the detection of RV with high sensitivity in comparison to conventional RT-PCR.",,"['Malik, Yashpal Singh', 'Sharma, Kuldeep', 'Kumar, Naveen', 'Shivachandra, Sathish B.', 'Rawat, Vinita', 'Rakholia, Ritu', 'Ranjan, Rajeev', 'Ganesh, Balasubramanian', 'Parida, ManMohan']",,,,
,PMC,A mastoparan-derived peptide has broad-spectrum antiviral activity against enveloped viruses,http://dx.doi.org/10.1016/j.peptides.2013.07.014,PMC3899704,,,"Broad-spectrum antiviral drugs are urgently needed to treat individuals infected with new and re-emerging viruses, or with viruses that have developed resistance to antiviral therapies. Mammalian natural host defense peptides (mNHP) are short, usually cationic, peptides that have direct antimicrobial activity, and which in some instances activate cell-mediated antiviral immune responses. Although mNHP have potent activity in vitro, efficacy trials in vivo of exogenously provided mNHP have been largely disappointing, and no mNHP are currently licensed for human use. Mastoparan is an invertebrate host defense peptide that penetrates lipid bilayers, and we reasoned that a mastoparan analog might interact with the lipid component of virus membranes and thereby reduce infectivity of enveloped viruses. Our objective was to determine whether mastoparan-derived peptide MP7-NH(2) could inactivate viruses of multiple types, and whether it could stimulate cell-mediated antiviral activity. We found that MP7-NH(2) potently inactivated a range of enveloped viruses. Consistent with our proposed mechanism of action, MP7-NH(2) was not efficacious against a non-enveloped virus. Pre-treatment of cells with MP7-NH(2) did not reduce the amount of virus recovered after infection, which suggested that the primary mechanism of action in vitro was direct inactivation of virus by MP7-NH(2). These results demonstrate for the first time that a mastoparan derivative has broad-spectrum antiviral activity in vitro and suggest that further investigation of the antiviral properties of mastoparan peptides in vivo is warranted.",,"['Sample, Christopher J.', 'Hudak, Kathryn E.', 'Barefoot, Brice E.', 'Koci, Matthew D.', 'Wanyonyi, Moses S.', 'Abraham, Soman', 'Staats, Herman F.', 'Ramsburg, Elizabeth A.']",,,,
,PMC,DNA vaccine prime followed by boost with live attenuated virus significantly improves antigen-specific T cell responses against human cytomegalovirus,http://dx.doi.org/10.4161/hv.25750,PMC3906396,,,"As a leading cause of congenital infection and a major threat to immunocompromised individuals, human cytomegalovirus (HCMV) is a major global public health concern. Effective HCMV vaccines would need to induce potent and balanced humoral and cellular immune responses. In this pilot study, immunogenicity studies were conducted in mice to examine HCMV antigen-specific antibody and T cell responses when a heterologous prime-boost immunization strategy was tested. DNA vaccines expressing either targets of protective antibody responses (gB and gM/gN) or well characterized T cell immunogens (pp65, pp150, and IE1) were used as the priming immunization while the live attenuated HCMV vaccine Towne strain was used as the boost, which may act like an inactivated vaccine due to the inability of HCMV to replicate in a mouse host. Our data indicate that while DNA vaccines were effective in priming HCMV-specific antibody responses, the final titers of gB- or gM-specific antibodies were not much different from those elicited by using multiple immunizations of HCMV alone. In contrast, DNA priming significantly enhanced T cell responses against gB, pp65, and IE1 as measured by IFN-γ. However, HCMV alone was not effective in eliciting strong T cell immune responses when used in a mouse host. Our data indicate that the complexity of antigen composition from a large virus, such as HCMV, may affect the profile of immune responses when viral vaccines are used as a boost.",,"['Gil, Anna', 'Shen, Siyuan', 'Coley, Scott', 'Gibson, Laura', 'Diamond, Don J', 'Wang, Shixia', 'Lu, Shan']",,,,
,PMC,Human rhinovirus infections of the lower respiratory tract in hematopoietic stem cell transplant recipients,http://dx.doi.org/10.1111/tid.12111,PMC3962254,,,"BACKGROUND: Human rhinoviruses (HRVs) are a common cause of upper respiratory infection (URI) in hematopoietic stem cell transplant (HSCT) recipients; yet, their role in lower respiratory illness is not well understood. METHODS: We performed a retrospective chart review of HSCT recipients with HRV infection from the time molecular detection methods were implemented at our institution in 2008. Factors associated with proven or possible HRV pneumonia at the first HRV detection were evaluated by univariate and multivariate analysis. We then characterized all episodes of proven and possible HRV pneumonia from the initial HRV infection through a 1-year follow-up period. RESULTS: Between 2008 and 2011, 63 HSCT recipients had ≥ 1 documented HRV infections. At first HRV detection, 36 (57%) patients had HRV URI and 27 (43%) had proven or possible HRV pneumonia; in multivariate analysis, hypoalbuminemia (odds ratio [OR] 9.5, 95% confidence interval [CI] 1.3–71.7; P=0.03) and isolation of respiratory co-pathogen(s) (OR 24.2, 95%CI 2.0–288.4; P=0.01) were independently associated with pneumonia. During the study period, 22 patients had 25 episodes of proven HRV pneumonia. Fever (60%), cough (92%), sputum production (61%), and dyspnea (60%) were common symptoms. Fifteen (60%) episodes demonstrated bacterial (n=n=7), fungal (n=n=5), or viral (n=n=3) co-infection. Among the remaining 10 (40%) cases of HRV monoinfection, patients’ oxygen saturations ranged from 80% to 97% on ambient air, and computed tomography scans showed peribronchiolar, patchy, ground glass infiltrates. CONCLUSIONS: HRV pneumonia is relatively common after HSCT and frequently accompanied by bacterial co-infection. As use of molecular assays for respiratory viral diagnosis becomes widespread, HRV will be increasingly recognized as a significant cause of pneumonia in immunocompromised hosts.",,"['Jacobs, S.E.', 'Soave, R.', 'Shore, T.B.', 'Satlin, M.J.', 'Schuetz, A.N.', 'Magro, C.', 'Jenkins, S.G.', 'Walsh, T.J.']",,,,
,PMC,"Outcomes of Hematopoietic Stem Cell Transplant Recipients with Rhinovirus Infection: A Matched, Case-Control Study",http://dx.doi.org/10.1038/bmt.2013.100,PMC4606879,,,"The impact of rhinovirus in hematopoietic stem cell transplant (HSCT) recipients is not well defined. A retrospective, matched, case-control study of HSCT recipients with rhinovirus was conducted between 2009 and 2011. Controls were matched for timing relative to transplant, malignancy, and stem cell source. There were 47 cases and 94 controls. Cases and controls did not differ with respect to age, gender, ethnicity, donor source, malignancy, conditioning regimen, immunosuppression, antimicrobial prophylaxis, or significant comorbidities. There were no differences in need for ICU care, 100 day mortality, hospice discharge, relapse of disease, GVHD or development of disease or infection due to CMV or EBV. Other infectious complications after rhinovirus diagnosis were also equal. However, there was an increased number of recurrent hospitalizations from any cause among cases (46.8% vs. 24.5%, P=0.007). Recurrent hospitalizations due to any infection were also more common in cases (34% vs. 14.9%, P=0.015). For patients who were diagnosed with rhinovirus pre-transplant (n=13), there was no difference in outcomes compared to matched controls. HSCT recipients with rhinovirus have an increased risk of hospital readmission. However, there was no difference in outcomes compared to matched controls. Transplantation in patients with active rhinovirus infection appears to be safe.",,"['Abandeh, Foad I.', 'Lustberg, Mark', 'Devine, Steven', 'Elder, Pat', 'Andritsos, Leslie', 'Martin, Stanley I.']",,,,
,PMC,Is low pathogenic avian influenza virus virulent for wild waterbirds?,http://dx.doi.org/10.1098/rspb.2013.0990,PMC3774239,,,"Although low pathogenic avian influenza virus (LPAIV) is traditionally considered to have adapted to its wild waterbird host to become avirulent, recent studies have suggested that LPAIV infection might after all have clinical effects. Therefore, I reviewed the literature on LPAIV infections in wild waterbirds. The virulence of LPAIV was assessed in 17 studies on experimental infections and nine studies on natural infections. Reported evidence for virulence were reductions in return rate, feeding rate, body weight, long-range movement and reproductive success, as well as pathological changes in infected organs. However, major caveats in studies of experimental infections were unnatural route of LPAIV inoculation, animal husbandry not simulating natural stressors and low sensitivity of clinical assessment. Major caveats in studies of natural infections were incomplete measurement of LPAIV infection burden, quasi-experimental design and potential misclassification of birds. After taking these caveats into account, the only remaining evidence for virulence was that presence and intensity of LPAIV infection were negatively correlated with body weight. Based on this correlation, together with the demonstrated LPAIV tropism for the intestinal tract, I hypothesize that LPAIV reduces digestive tract function, and suggest how future studies could be directed to test this hypothesis.",,"Kuiken, Thijs",,,,
,PMC,"Homologous 2′,5′-phosphodiesterases from disparate RNA viruses antagonize antiviral innate immunity",http://dx.doi.org/10.1073/pnas.1306917110,PMC3740845,,,"Efficient and productive virus infection often requires viral countermeasures that block innate immunity. The IFN-inducible 2′,5′-oligoadenylate (2-5A) synthetases (OASs) and ribonuclease (RNase) L are components of a potent host antiviral pathway. We previously showed that murine coronavirus (MHV) accessory protein ns2, a 2H phosphoesterase superfamily member, is a phosphodiesterase (PDE) that cleaves 2-5A, thereby preventing activation of RNase L. The PDE activity of ns2 is required for MHV replication in macrophages and for hepatitis. Here, we show that group A rotavirus (RVA), an important cause of acute gastroenteritis in children worldwide, encodes a similar PDE. The RVA PDE forms the carboxy-terminal domain of the minor core protein VP3 (VP3-CTD) and shares sequence and predicted structural homology with ns2, including two catalytic HxT/S motifs. Bacterially expressed VP3-CTD exhibited 2′,5′-PDE activity, which cleaved 2-5A in vitro. In addition, VP3-CTD expressed transiently in mammalian cells depleted 2-5A levels induced by OAS activation with poly(rI):poly(rC), preventing RNase L activation. In the context of recombinant chimeric MHV expressing inactive ns2, VP3-CTD restored the ability of the virus to replicate efficiently in macrophages or in the livers of infected mice, whereas mutant viruses expressing inactive VP3-CTD (H718A or H798R) were attenuated. In addition, chimeric viruses expressing either active ns2 or VP3-CTD, but not nonfunctional equivalents, were able to protect ribosomal RNA from RNase L–mediated degradation. Thus, VP3-CTD is a 2′,5′-PDE able to functionally substitute for ns2 in MHV infection. Remarkably, therefore, two disparate RNA viruses encode proteins with homologous 2′,5′-PDEs that antagonize activation of innate immunity.",,"['Zhang, Rong', 'Jha, Babal K.', 'Ogden, Kristen M.', 'Dong, Beihua', 'Zhao, Ling', 'Elliott, Ruth', 'Patton, John T.', 'Silverman, Robert H.', 'Weiss, Susan R.']",,,,
,PMC,Romance of the three domains: how cladistics transformed the classification of cellular organisms,http://dx.doi.org/10.1007/s13238-013-3050-9,PMC4875529,,,"Cladistics is a biological philosophy that uses genealogical relationship among species and an inferred sequence of divergence as the basis of classification. This review critically surveys the chronological development of biological classification from Aristotle through our postgenomic era with a central focus on cladistics. In 1957, Julian Huxley coined cladogenesis to denote splitting from subspeciation. In 1960, the English translation of Willi Hennig’s 1950 work, Systematic Phylogenetics, was published, which received strong opposition from pheneticists, such as numerical taxonomists Peter Sneath and Robert Sokal, and evolutionary taxonomist, Ernst Mayr, and sparked acrimonious debates in 1960–1980. In 1977–1990, Carl Woese pioneered in using small subunit rRNA gene sequences to delimitate the three domains of cellular life and established major prokaryotic phyla. Cladistics has since dominated taxonomy. Despite being compatible with modern microbiological observations, i.e. organisms with unusual phenotypes, restricted expression of characteristics and occasionally being uncultivable, increasing recognition of pervasiveness and abundance of horizontal gene transfer has challenged relevance and validity of cladistics. The mosaic nature of eukaryotic and prokaryotic genomes was also gradually discovered. In the mid-2000s, high-throughput and whole-genome sequencing became routine and complex geneologies of organisms have led to the proposal of a reticulated web of life. While genomics only indirectly leads to understanding of functional adaptations to ecological niches, computational modeling of entire organisms is underway and the gap between genomics and phenetics may soon be bridged. Controversies are not expected to settle as taxonomic classifications shall remain subjective to serve the human scientist, not the classified.",,"['Ho, Chi-Chun', 'Lau, Susanna K. P.', 'Woo, Patrick C. Y.']",,,,
,PMC,The inhibitory effect of G(βγ) and G(β) isoform specificity on ENaC activity,http://dx.doi.org/10.1152/ajprenal.00009.2013,PMC3840225,,,"Epithelial Na(+) channel (ENaC) activity, which determines the rate of renal Na(+) reabsorption, can be regulated by G protein-coupled receptors. Regulation of ENaC by Gα-mediated downstream effectors has been studied extensively, but the effect of G(βγ) dimers on ENaC is unclear. A6 cells endogenously contain high levels of G(β1) but low levels of G(β3), G(β4), and G(β5) were detected by Q-PCR. We tested Gγ(2) combined individually with G(β1) through G(β5) expressed in A6 cells, after which we recorded single-channel ENaC activity. Among the five β and γ(2) combinations, β(1)γ(2) strongly inhibits ENaC activity by reducing both ENaC channel number (N) and open probability (P(o)) compared with control cells. In contrast, the other four β-isoforms combined with γ(2) have no significant effect on ENaC activity. By using various inhibitors to probe G(β1γ2) effects on ENaC regulation, we found that G(β1γ2)-mediated ENaC inhibition involved activation of phospholipase C-β and its enzymatic products that induce protein kinase C and ERK1/2 signaling pathways.",,"['Yu, Ling', 'Al-Khalili, Otor', 'Duke, Billie Jeanne', 'Stockand, James D.', 'Eaton, Douglas C.', 'Bao, Hui-Fang']",,,,
,PMC,Potential for the International Spread of Middle East Respiratory Syndrome in Association with Mass Gatherings in Saudi Arabia,http://dx.doi.org/10.1371/currents.outbreaks.a7b70897ac2fa4f79b59f90d24c860b8,PMC3714242,23884087,CC BY,"Background: A novel coronavirus (MERS-CoV) causing severe, life-threatening respiratory disease has emerged in the Middle East at a time when two international mass gatherings in Saudi Arabia are imminent. While MERS-CoV has already spread to and within other countries, these mass gatherings could further amplify and/or accelerate its international dissemination, especially since the origins and geographic source of the virus remain poorly understood. Methods: We analyzed 2012 worldwide flight itinerary data and historic Hajj pilgrim data to predict population movements out of Saudi Arabia and the broader Middle East to help cities and countries assess their potential for MERS-CoV importation. We compared the magnitude of travel to countries with their World Bank economic status and per capita healthcare expenditures as surrogate markers of their capacity for timely detection of imported MERS-CoV and their ability to mount an effective public health response. Results: 16.8 million travelers flew on commercial flights out of Saudi Arabia, Jordan, Qatar, and the United Arab Emirates between June and November 2012, of which 51.6% were destined for India (16.3%), Egypt (10.4%), Pakistan (7.8%), the United Kingdom (4.3%), Kuwait (3.6%), Bangladesh (3.1%), Iran (3.1%) and Bahrain (2.9%). Among the 1.74 million foreign pilgrims who performed the Hajj last year, an estimated 65.1% originated from low and lower-middle income countries. Conclusion: MERS-CoV is an emerging pathogen with pandemic potential with its apparent epicenter in Saudi Arabia, where millions of pilgrims will imminently congregate for two international mass gatherings. Understanding global population movements out of the Middle East through the end of this year's Hajj could help direct anticipatory MERS-CoV surveillance and public health preparedness to mitigate its potential global health and economic impacts.",2013 Jul 17,"['Khan, Kamran', 'Sears, Jennifer', 'Hu, Vivian Wei', 'Brownstein, John S', 'Hay, Simon', 'Kossowsky, David', 'Eckhardt, Rose', 'Chim, Tina', 'Berry, Isha', 'Bogoch, Isaac', 'Cetron, Martin']",PLoS Curr,,,
,PMC,Home Self-Collection of Nasal Swabs for Diagnosis of Acute Respiratory Virus Infections in Children With Cystic Fibrosis,http://dx.doi.org/10.1093/jpids/pit039,PMC3869469,,,"BACKGROUND: Understanding the importance of respiratory viruses in children with cystic fibrosis (CF) has been limited because of challenges using clinic- or hospital-based diagnostic testing. We conducted a pilot study to assess feasibility of home self- (or parent-) collection of nasal swabs (NS). METHODS: Cystic fibrosis patients aged 6–18 years with new respiratory illness participated. In clinic, a deep nasal flocked swab was collected by research staff and compared with an anterior foam NS obtained after instillation of saline spray. At home, up to 2 self-collections of paired foam NS (with and without saline) were collected and mailed for real-time polymerase chain reaction (PCR) testing. RESULTS: Paired swabs were collected from 28 patients: 18 sets in clinic (deep nasal vs saline foam NS) and 43 sets at home (saline vs dry foam NS) with 9 (50%) and 35 (81%) virus detections, respectively. Home-collected NS were obtained closer to illness onset, with a mean difference in symptom days of −2.3 between home and clinic collections (95% confidence interval [CI] −3.5, −1.2; P < .001). Rhinovirus comprised 73% of virus detections; the difference in mean PCR cycle threshold values for rhinovirus between swabs collected at home versus clinic was −3.8 (95% CI −6.8, −0.9; P = .014), indicating significantly higher viral load for home-collected swabs. CONCLUSIONS: Home-collected foam NS had a higher positivity rate compared with clinic-collected swabs, likely because collection was closer to illness onset. Home self-collection is feasible and well tolerated for timely respiratory virus diagnosis and provides a novel approach for clinical diagnostics and surveillance of respiratory virus infections among CF patients.",,"['Emerson, Julia', 'Cochrane, Elizabeth', 'McNamara, Sharon', 'Kuypers, Jane', 'Gibson, Ronald L.', 'Campbell, Angela P.']",,,,
,PMC,A virocentric perspective on the evolution of life,http://dx.doi.org/10.1016/j.coviro.2013.06.008,PMC4326007,,,"Viruses and/or virus-like selfish elements are associated with all cellular life forms and are the most abundant biological entities on Earth, with the number of virus particles in many environments exceeding the number of cells by one to two orders of magnitude. The genetic diversity of viruses is commensurately enormous and might substantially exceed the diversity of cellular organisms. Unlike cellular organisms with their uniform replication-expression scheme, viruses possess either RNA or DNA genomes and exploit all conceivable replication-expression strategies. Although viruses extensively exchange genes with their hosts, there exists a set of viral hallmark genes that are shared by extremely diverse groups of viruses to the exclusion of cellular life forms. Coevolution of viruses and host defense systems is a key aspect in the evolution of both viruses and cells, and viral genes are often recruited for cellular functions. Together with the fundamental inevitability of the emergence of genomic parasites in any evolving replicator system, these multiple lines of evidence reveal the central role of viruses in the entire evolution of life.",,"['Koonin, Eugene V.', 'Dolja, Valerian V.']",,,,
,PMC,Potent monoclonal antibodies against Clostridium difficile toxin A elicited by DNA immunization,http://dx.doi.org/10.4161/hv.25656,PMC3906400,,,"Recent studies have demonstrated that DNA immunization is effective in eliciting antigen-specific antibody responses against a wide range of infectious disease targets. The polyclonal antibodies elicited by DNA vaccination exhibit high sensitivity to conformational epitopes and high avidity. However, there have been limited reports in literature on the production of monoclonal antibodies (mAb) by DNA immunization. Here, by using Clostridium difficile (C. diff) toxin A as a model antigen, we demonstrated that DNA immunization was effective in producing a panel of mAb that are protective against toxin A challenge and can also be used as sensitive reagents to detect toxin A from various testing samples. The immunoglobulin (Ig) gene usage for such mAb was also investigated. Further studies should be conducted to fully establish DNA immunization as a unique platform to produce mAb in various hosts.",,"['Zhang, Chunhua', 'Jin, Ke', 'Xiao, Yanling', 'Cheng, Ying', 'Huang, Zuhu', 'Wang, Shixia', 'Lu, Shan']",,,,
,PMC,Implications of DPP4 modification of proteins that regulate stem/progenitor and more mature cell types,http://dx.doi.org/10.1182/blood-2013-02-487470,PMC3709652,,,"Dipeptidylpeptidase (DPP) 4 has the potential to truncate proteins with a penultimate alanine, proline, or other selective amino acids at the N-terminus. DPP4 truncation of certain chemokines, colony-stimulating factors, and interleukins have recently been linked to regulation of hematopoietic stem/progenitor cells, more mature blood cells, and other cell types. We believe that the potential role of DPP4 in modification of many regulatory proteins, and their subsequent effects on numerous stem/progenitor and other cell-type functions has not been adequately appreciated. This review addresses the potential implications of the modifying effects of DPP4 on a large number of cytokines and other growth-regulating factors with either proven or putative DPP4 truncation sites on hematopoietic cells, and subsequent effects of DPP4-truncated proteins on multiple aspects of steady-state and stressed hematopoiesis, including stem/progenitor cell, and more mature cell, function.",,"['Ou, Xuan', 'O’Leary, Heather A.', 'Broxmeyer, Hal E.']",,,,
,PMC,Viral evasion mechanisms of early antiviral responses involving regulation of ubiquitin pathways,http://dx.doi.org/10.1016/j.tim.2013.06.006,PMC3740364,,,"Early innate and cell-intrinsic responses are essential to protect host cells against pathogens. In turn, viruses have developed sophisticated mechanisms to establish productive infections, counteracting the host innate immune responses. Increasing evidence indicates that these antiviral factors may have a dual role by directly inhibiting viral replication, as well as by sensing and transmitting signals to induce antiviral cytokines. Recent studies have pointed at new, unappreciated mechanisms of viral evasion of host innate protective responses including manipulating the host ubiquitin system. Viral inhibition of antiviral factors by ubiquitin-dependent degradation is emerging as critical evasion mechanism of the antiviral response. In addition, recent studies have uncovered new mechanisms by which viral encoded proteins inhibit ubiquitin and ubiquitin-like modification of host proteins involved innate immune signaling pathways. Here we discuss recent findings and novel strategies that viruses have developed to counteract these early innate antiviral defenses.",,"['Rajsbaum, Ricardo', 'García-Sastre, Adolfo']",,,,
,PMC,Acute disseminated encephalomyelitis following infectious mononucleosis in a toddler,http://dx.doi.org/10.1136/bcr-2013-010048,PMC3736176,,,"Symptomatic Epstein-Barr virus (EBV) infection complicated by acute disseminated encephalomyelitis (ADEM) in a toddler is rare. Our patient is a 14 month-old boy who presented with listlessness and reduced eye movements nearly 10 days after a prodromal upper respiratory illness that was accompanied by an amoxicillin rash. On examination, the boy appeared drowsy, had a congested throat and a resolving lower extremity rash, but otherwise had a normal neurological examination. Investigation revealed lymphocytosis, mildly elevated liver enzyme and a positive EBV IgM serology. Cerebrospinal fluid analysis showed pleocytosis. Subsequent brain and spine MRI showed demyelinating disease extending from the cerebral peduncles, across the brain stem and down to the mid-thoracic spinal cord. The patient was treated as a case of ADEM and given intravenous methylprednisolone. On outpatient follow-up his symptoms resolved completely in 6 weeks.",,"['Mohsen, Hassan', 'Abu Zeinah, Ghaith Farid', 'Elsotouhy, Ahmed Hassan', 'Mohamed, Khalid']",,,,
,PMC,Correspondence (reply): In Reply,http://dx.doi.org/10.3238/arztebl.2013.0486,PMC3722646,,,,,"['Müller, Thomas', 'Bein, Thomas']",,,,
,PMC,Hantaviruses as Zoonotic Pathogens in Germany,http://dx.doi.org/10.3238/arztebl.2013.0461,PMC3722641,,,"BACKGROUND: Hantavirus disease is a zoonosis of increasing clinical importance. A new incidence peak was reached in Germany in 2012, with more than 2800 reported cases. These viruses are transmitted from small mammals to human beings. The disease begins with high fever and non-pathognomonic manifestations that can end in shock and organ failure. METHODS: This article is based on a selective literature search, on the authors’ experiences at the National Referral Laboratory for Hantavirus Infections (Nationales Konsiliarlaboratorium für Hantaviren), and on published recommendations from Germany and abroad. RESULTS: Two hantavirus species cause clinically relevant infections in Germany. Puumala virus, which is transmitted by bank voles, causes large outbreaks of disease every 2 to 3 years in the southwestern and western regions of Germany and in the Bavarian Forest. Dobrava-Belgrad virus, transmitted by striped field mice, causes infections in the north and east of the country. Serological tests are available for primary and confirmatory diagnosis; moreover, viral nucleic acids can be amplified in the early phase of illness and compared with the viral nucleic acids from the reservoir hosts of the corresponding type of infection. Infections with American types of hantavirus have ca. 35% case fatality, and hantaviruses from southeastern Europe and Asia are also highly pathogenic; in contrast, the febrile illnesses caused by hantaviruses in Germany are usually relatively mild. CONCLUSION: When persons living in high-risk areas present with fever of unknown origin or with renal dysfunction of unknown origin, physicians should consider the possibility of a hantavirus infection and should initiate the appropriate diagnostic evaluation.",,"['Krüger, Detlev H', 'Ulrich, Rainer G', 'Hofmann, Jörg']",,,,
,PMC,Phage ϕ29 protein p1 promotes replication by associating with the FtsZ ring of the divisome in Bacillus subtilis,http://dx.doi.org/10.1073/pnas.1311524110,PMC3725111,,,"During evolution, viruses have optimized the interaction with host factors to increase the efficiency of fundamental processes such as DNA replication. Bacteriophage ϕ29 protein p1 is a membrane-associated protein that forms large protofilament sheets that resemble eukaryotic tubulin and bacterial filamenting temperature-sensitive mutant Z protein (FtsZ) polymers. In the absence of protein p1, phage ϕ29 DNA replication is impaired. Here we show that a functional fusion of protein p1 to YFP localizes at the medial region of Bacillus subtilis cells independently of other phage-encoded proteins. We also show that ϕ29 protein p1 colocalizes with the B. subtilis cell division protein FtsZ and provide evidence that FtsZ and protein p1 are associated. Importantly, the midcell localization of YFP-p1 was disrupted in a strain that does not express FtsZ, and the fluorescent signal was distributed all over the cell. Depletion of penicillin-binding protein 2B (PBP2B) in B. subtilis cells did not affect the subcellular localization of YFP-p1, indicating that its distribution does not depend on septal wall synthesis. Interestingly, when ϕ29 protein p1 was expressed, B. subtilis cells were about 1.5-fold longer than control cells, and the accumulation of ϕ29 DNA was higher in mutant B. subtilis cells with increased length. We discuss the biological role of p1 and FtsZ in the ϕ29 growth cycle.",,"['Ballesteros-Plaza, David', 'Holguera, Isabel', 'Scheffers, Dirk-Jan', 'Salas, Margarita', 'Muñoz-Espín, Daniel']",,,,
,PMC,Within-mother analysis of seasonal patterns in health at birth,http://dx.doi.org/10.1073/pnas.1307582110,PMC3725083,,,"A large literature describes relationships between month of birth, birth weight, and gestation. These relationships are hypothesized to reflect the causal impact of seasonal environmental factors. However, recent work casts doubt on this interpretation by showing that mothers with lower socioeconomic status are more likely to give birth in months that are associated with poorer birth outcomes. Seasonality in the numbers of conceptions in different months can also induce a mechanical correlation between preterm birth and month of birth. This paper analyzes the seasonality of health at birth using a large sample of 647,050 groups of US siblings representing 1,435,213 children. By following the same mother over time, we eliminate differences in fixed maternal characteristics as an explanation for seasonal differences in health at birth. We find a sharp trough in gestation length among babies conceived in May, which corresponds to an increase in prematurity of more than 10%. Birth weight conditional on gestation length, however, is found to be strongly hump-shaped over the year, with 8–9 additional g for summer conceptions. We examine several potential mechanisms for explaining seasonality in birth outcomes that have generally been dismissed in the literature on seasonality in rich countries, notably disease prevalence and nutrition. The May trough in gestation length coincides with a higher influenza prevalence in January and February, when these babies are nearing full term, whereas the hump shape in birth weight is associated with a similar pattern in pregnancy weight gain.",,"['Currie, Janet', 'Schwandt, Hannes']",,,,
,PMC,Involvement of high mobility group box 1 and the therapeutic effect of recombinant thrombomodulin in a mouse model of severe acute respiratory distress syndrome,http://dx.doi.org/10.1111/cei.12106,PMC3722928,,,"Acute respiratory distress syndrome (ARDS) is accompanied by severe lung inflammation induced by various diseases. Despite the severity of the symptoms, therapeutic strategies have been ineffective. High mobility group box 1 (HMGB1), which was identified originally as a DNA binding protein, has been proposed as a mediator of acute lung injury. In addition to its anti-coagulant activity, recombinant thrombomodulin (rTM) possesses an ability to suppress the inflammatory response through neutralizing HMGB1. T regulatory (T(reg)) cells in the lungs are reported to modify innate immune responses during resolution of acute lung injury. In the present study, we investigated the therapeutic effect of rTM, and the contribution of T(reg) cells to this effect, in a mouse model of severe ARDS. C57BL/6 mice received sequential intratracheal administration of α-galactosylceramide (α-GalCer) and lipopolysaccharide (LPS), which resulted in the development of severe ARDS. HMGB1 levels in the lungs increased to a higher level in ARDS mice compared to those in mice treated with LPS alone. HMGB1 was expressed in the infiltrating neutrophils and macrophages in lungs. T(reg) cells were reduced significantly in the lungs of ARDS mice compared to those in mice treated with LPS alone. rTM administration prolonged the survival time and ameliorated the development of ARDS, which was associated with increased T(reg) cells and synthesis of interleukin (IL)-10 and transforming growth factor (TGF)-β in the lungs. These results suggest that HMGB1 is involved in the development of severe ARDS and rTM shows therapeutic effects through promoting the accumulation of T(reg) cells at the inflammatory sites.",,"['Kudo, D', 'Toyama, M', 'Aoyagi, T', 'Akahori, Y', 'Yamamoto, H', 'Ishii, K', 'Kanno, E', 'Maruyama, R', 'Kaku, M', 'Kushimoto, S', 'Kawakami, K']",,,,
,PMC,Accommodation of large cargo within Golgi cisternae,http://dx.doi.org/10.1007/s00418-013-1120-y,PMC3756474,,,"In mammalian cells, the Golgi complex has an elaborate structure consisting of stacked, flattened cisternal membranes collected into a ribbon in the center of the cell. Amazingly, the flattened cisternae can rapidly dilate to accommodate large cargo as it traffics through the organelle. The mechanism by which this occurs is unknown. Exocytosis of large cargo is essential for many physiological processes, including collagen and lipoprotein secretion, and defects in the process lead to disease. In addition, enveloped viruses that bud into the endoplasmic reticulum or Golgi complex must also be transported through Golgi cisternae for secretion from the infected cell. This review summarizes our understanding of intra-Golgi transport of large cargo, and outlines current questions open for experimentation.",,"Machamer, Carolyn E.",,,,
,PMC,Bcl2-associated Athanogene 3 Interactome Analysis Reveals a New Role in Modulating Proteasome Activity,http://dx.doi.org/10.1074/mcp.M112.025882,PMC3790292,,,"Bcl2-associated athanogene 3 (BAG3), a member of the BAG family of co-chaperones, plays a critical role in regulating apoptosis, development, cell motility, autophagy, and tumor metastasis and in mediating cell adaptive responses to stressful stimuli. BAG3 carries a BAG domain, a WW domain, and a proline-rich repeat (PXXP), all of which mediate binding to different partners. To elucidate BAG3's interaction network at the molecular level, we employed quantitative immunoprecipitation combined with knockdown and human proteome microarrays to comprehensively profile the BAG3 interactome in humans. We identified a total of 382 BAG3-interacting proteins with diverse functions, including transferase activity, nucleic acid binding, transcription factors, proteases, and chaperones, suggesting that BAG3 is a critical regulator of diverse cellular functions. In addition, we characterized interactions between BAG3 and some of its newly identified partners in greater detail. In particular, bioinformatic analysis revealed that the BAG3 interactome is strongly enriched in proteins functioning within the proteasome-ubiquitination process and that compose the proteasome complex itself, suggesting that a critical biological function of BAG3 is associated with the proteasome. Functional studies demonstrated that BAG3 indeed interacts with the proteasome and modulates its activity, sustaining cell survival and underlying resistance to therapy through the down-modulation of apoptosis. Taken as a whole, this study expands our knowledge of the BAG3 interactome, provides a valuable resource for understanding how BAG3 affects different cellular functions, and demonstrates that biologically relevant data can be harvested using this kind of integrated approach.",,"['Chen, Ying', 'Yang, Li-Na', 'Cheng, Li', 'Tu, Shun', 'Guo, Shu-Juan', 'Le, Huang-Ying', 'Xiong, Qian', 'Mo, Ran', 'Li, Chong-Yang', 'Jeong, Jun-Seop', 'Jiang, Lizhi', 'Blackshaw, Seth', 'Bi, Li-Jun', 'Zhu, Heng', 'Tao, Sheng-Ce', 'Ge, Feng']",,,,
,PMC,Influenza A (H7N9) and the Importance of Digital Epidemiology,http://dx.doi.org/10.1056/NEJMp1307752,PMC4873163,,,,,"['Salathé, Marcel', 'Freifeld, Clark C.', 'Mekaru, Sumiko R.', 'Tomasulo, Anna F.', 'Brownstein, John S.']",,,,
,PMC,A Comparative High-Throughput Screening Protocol to Identify Entry Inhibitors of Enveloped Viruses,http://dx.doi.org/10.1177/1087057113494405,PMC4679145,,,"Emerging and reemerging human viral pathogens pose great public health concerns since therapeutics against these viruses are limited. Thus, there is an urgent need to develop novel drugs that can block infection of either a specific virus or a number of viruses. Viral entry is thought to be an ideal target for potential therapeutic prevention. One of the challenges of developing antivirals is that most of these viruses are highly pathogenic and therefore require high biosafety-level containment. In this study, we have adopted a comparative high-throughput screening protocol to identify entry inhibitors for three enveloped viruses (Marburg virus, influenza virus H5N1, and Lassa virus) using a human immunodeficiency virus–based pseudotyping platform. We demonstrate the utility of this approach by screening a small compound library and identifying putative entry inhibitors for these viruses. One major advantage of this protocol is to reduce the number of false positives in hit selection, and we believe that the protocol is useful for inhibitor screening for many enveloped viruses.",,"['Wang, Juan', 'Cheng, Han', 'Ratia, Kiira', 'Varhegyi, Elizabeth', 'Hendrickson, William G.', 'Li, Juan', 'Rong, Lijun']",,,,
,PMC,"Poliovirus infection induces the co-localization of cellular protein SRp20 with TIA-1, a cytoplasmic stress granule protein",http://dx.doi.org/10.1016/j.virusres.2013.06.012,PMC3742715,,,"Different types of environmental stress cause mammalian cells to form cytoplasmic foci, termed stress granules, which contain mRNPs that are translationally silenced. These foci are transient and dynamic, and contain components of the cellular translation machinery as well as certain mRNAs and RNA binding proteins. Stress granules are known to be induced by conditions such as hypoxia, nutrient deprivation, and oxidative stress, and a number of cellular factors have been identified that are commonly associated with these foci. More recently it was discovered that poliovirus infection also induces the formation of stress granules, although these cytoplasmic foci appear to be somewhat compositionally unique. Work described here examined the punctate pattern of SRp20 (a host cell mRNA splicing protein) localization in the cytoplasm of poliovirus-infected cells, demonstrating the partial co-localization of SRp20 with the stress granule marker protein TIA-1. We determined that SRp20 does not co-localize with TIA-1, however, under conditions of oxidative stress, indicating that the close association of these two proteins during poliovirus infection is not representative of a general response to cellular stress. We confirmed that the expression of a dominant negative version of TIA-1 (TIA-1-PRD) results in the dissociation of stress granules. Finally, we demonstrated that expression of wild type TIA-1 or dominant negative TIA-1-PRD in cells during poliovirus infection does not dramatically affect viral translation. Taken together, these studies provide a new example of the unique cytoplasmic foci that form during poliovirus infection.",,"['Fitzgerald, Kerry D.', 'Semler, Bert L.']",,,,
,PMC,The legacies of SARS – international preparedness and readiness to respond to future threats in the Western Pacific Region,http://dx.doi.org/10.5365/WPSAR.2013.4.3-004,PMC3854097,,,,,"['Mackenzie, John S', 'Merianos, Angela']",,,,
,PMC,Revisiting Public Health Challenges in the New Millennium,http://dx.doi.org/10.4103/2141-9248.117923,PMC3793429,24116303,CC BY-NC-SA,"Positive Health of the communities could only be brought out through the interrelationship between conventional health sector and other development sectors. It was a dream that came true when World Health Organization (WHO) accepted Primary Health Care (PHC) as the major tool to achieve its proposed goal of Health For All (HFA) by 2000 A.D., but we could not succeed as expected. Now we have the Millennium Development Goals (MDG), which place health at the heart of development but the achievements in health is still challenging. The literature search in this article has been conducted in Pub Med and Google scholar, with the aim to draw references to discuss the major health issues and ways to tackle them. The current article briefly narrates the burden and complexities of challenges faced by the present global health. Revisiting the concept of PHC and reaffirming our solidarity to this philosophy is the need of this hour.",2013 Jul-Sep,"['Anish, TS', 'Sreelakshmi, PR']",Ann Med Health Sci Res,,,
,PMC,Association of bronchoalveolar lavage yield with chest computed tomography findings and symptoms in immunocompromised patients,http://dx.doi.org/10.4103/1817-1737.114302,PMC3731857,23922610,CC BY-NC-SA,"INTRODUCTION: Fiber-optic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) is a common procedure performed in immunocompromised patients with undiagnosed pulmonary pathology. Identifying patients with the highest potential diagnostic yield may help to avoid morbidity in patients unlikely to benefit from the procedure. We sought to determine which patient factors, specifically chest computed tomography (CT) findings, affected diagnostic yield of BAL. METHODS: Retrospective chart review of immunocompromised patients who underwent FOB with BAL from 01/01/2010 to 12/31/2011 at an academic medical center was performed. The lung lobe lavaged, characteristics of pulmonary infiltrate on radiograph, patient symptoms, and diagnostic yield were collected. A positive diagnostic yield was defined as a positive microbiological culture, finding on cytopathologic staining, diffuse alveolar hemorrhage, alveolar eosinophilia or a positive immunologic or nucleic acid assay. RESULTS: The overall diagnostic yield was 52.6%. Infiltrates that were predominantly reticular or nodular by CT had a lower diagnostic yield than predominantly consolidated, ground-glass, or tree-in-bud infiltrates (36.5% vs. 61.2%, P = 0.0058). The diagnostic yield was significantly improved in patients with both fever and chest symptoms compared to patients without symptoms (61.3% vs. 29.6%, P = 0.0066). CONCLUSION: CT findings of reticular and nodular infiltrates portend a worse diagnostic yield from BAL than those that are alveolar in nature. Symptomatic patients are more likely to have diagnostic FOB with BAL than asymptomatic patients.",2013 Jul-Sep,"['Brownback, Kyle R.', 'Simpson, Steven Q.']",Ann Thorac Med,,,
,PMC,Phosphatidylinositol 4-Kinase III Beta Is Essential for Replication of Human Rhinovirus and Its Inhibition Causes a Lethal Phenotype In Vivo,http://dx.doi.org/10.1128/AAC.00303-13,PMC3697394,,,"Human rhinovirus (HRV) is the predominant cause of the common cold, but more importantly, infection may have serious repercussions in asthmatics and chronic obstructive pulmonary disorder (COPD) patients. A cell-based antiviral screen against HRV was performed with a subset of our proprietary compound collection, and an aminothiazole series with pan-HRV species and enteroviral activity was identified. The series was found to act at the level of replication in the HRV infectious cycle. In vitro selection and sequencing of aminothiazole series-resistant HRV variants revealed a single-nucleotide mutation leading to the amino acid change I42V in the essential HRV 3A protein. This same mutation has been previously implicated in resistance to enviroxime, a former clinical-stage antipicornavirus agent. Enviroxime-like compounds have recently been shown to target the lipid kinase phosphatidylinositol 4-kinase III beta (PI4KIIIβ). A good correlation between PI4KIIIβ activity and HRV antiviral potency was found when analyzing the data over 80 compounds of the aminothiazole series, covering a 750-fold potency range. The mechanism of action through PI4KIIIβ inhibition was further demonstrated by small interfering RNA (siRNA) knockdown of PI4KB, which reduced HRV replication and also increased the potency of the PI4KIIIβ inhibitors. Inhibitors from two different structural classes with promising pharmacokinetic profiles and with very good selectivity for PI4KIIIβ were used to dissociate compound-related toxicity from target-related toxicity. Mortality was seen in all dosing groups of mice treated with either compound, therefore suggesting that short-term inhibition of PI4KIIIβ is deleterious.",,"['Spickler, Catherine', 'Lippens, Julie', 'Laberge, Marie-Kristine', 'Desmeules, Sophie', 'Bellavance, Édith', 'Garneau, Michel', 'Guo, Tim', 'Hucke, Oliver', 'Leyssen, Pieter', 'Neyts, Johan', 'Vaillancourt, Fréderic H.', 'Décor, Anne', ""O'Meara, Jeff"", 'Franti, Michael', 'Gauthier, Annick']",,,,
,PMC,"RACE, GENDER AND TOTAL KNEE REPLACEMENT CONSIDERATION: THE ROLE OF SOCIAL SUPPORT",http://dx.doi.org/10.1002/acr.21925,PMC4431890,,,"OBJECTIVE: To determine whether there are racial differences in social support among patients with knee osteoarthritis (OA) and whether the impact of social support on patient preferences for total knee replacement (TKR) varies by race and gender. METHODS: 514 white & 285 African-American (AA) patients with knee OA were surveyed. Logistic regression models were performed to determine if the relationship between willingness to undergo TKR and the interaction of patient race and sex were mediated by social support. RESULTS: Compared to whites with knee OA, AA patients were less likely to be married (p<0.001), reported less close friends/relatives (p<0.001) and had lower Medical Outcomes Study-Social Support Scale (MOS-SSS) scores (p<0.001). AA patients were also less willing to undergo TKR (62% vs. 80%, p<0.001) than whites. The odds of willingness to undergo TKR was less in white females compared to white males when adjusted for recruitment site, age, income and WOMAC (OR 0.57, 95% CI 0.34–0.96). This difference was no longer significant when further adjusted for marital status, number of close friends/relatives and MOS-SSS score, but the effect size remained unchanged (OR 0.60, 95% CI 0.35–1.02). The odds of willingness to undergo TKR remained much less in AA females (OR 0.35, 95% CI 0.19–0.64) and AA males (OR 0.28, 95% CI 0.14–0.54) compared to white males when controlled for sociodemographic, clinical and social support measures. CONCLUSIONS: AA patients reported less structural and functional social support than whites. Social support is an important determinant of preference for TKR surgery only among whites.",,"['Vina, Ernest R.', 'Cloonan, Yona K.', 'Ibrahim, Said A.', 'Hannon, Michael J.', 'Boudreau, Robert M.', 'Kwoh, C. Kent']",,,,
,PMC,H7N9 influenza-the laboratory presentations: A letter to editor,http://dx.doi.org/10.1016/S2221-1691(13)60118-5,PMC3695587,,,,,"Wiwanitkit, Viroj",,,,
,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.13.010713,PMC3699801,,,,,,,,,
,PMC,Public Health Watch,http://dx.doi.org/10.1177/1715163513494597,PMC3734925,,,,,"Lynas, Kathie",,,,
,PMC,Cytolytic Activity of the Human Papillomavirus Type 16 E7(11-20) Epitope-Specific Cytotoxic T Lymphocyte Is Enhanced by Heat Shock Protein 110 in HLA-A*0201 Transgenic Mice,http://dx.doi.org/10.1128/CVI.00721-12,PMC3697441,,,"Heat shock proteins (HSPs) have been successfully applied to a broad range of vaccines as biological adjuvants to enhance the immune response. The recently defined HSP110, in particular, exhibits strong protein binding affinity and is capable of enhancing the immunogenicity of protein antigens remarkably more than other HSP family members. In our previous study, we verified that murine HSP110 (mHSP110) significantly enhanced the immune response of a C57BL/6 mouse model to the H-2(d)-restricted human papillomavirus (HPV) E7(49-57) epitope (short peptide spanning the 49th to 57th amino acid residues in the E7 protein). To determine whether HSP110 similarly enhances the immunogenicity of human epitope peptides, we used the HLA-A2 transgenic mouse model to investigate the efficacy of the mHSP110 chaperone molecule as an immunoadjuvant of the human HLA-A2-restricted HPV16 E7(11-20) epitope vaccine. Results showed that mHSP110 efficiently formed a noncovalently bound complex with the E7(11-20) epitope. The mHSP110-E7(11-20) complex induced epitope-specific splenocyte proliferation and E7(11-20)-specific gamma interferon (IFN-γ) secretion. Importantly, cytotoxic T lymphocytes primed by the mHSP110-E7(11-20) complex exerted strong cytolytic effects on target T(2) cells pulsed with the E7(11-20) peptide or TC-1 cells transfected with the HLA-A2 gene. In addition, the mHSP110-E7(11-20) complex elicited stronger ex vivo and in vivo antitumor responses than either emulsified complete Freund's adjuvant or HSP70-chaperoned E7(11-20) peptide. These collective data suggest that HSP110 is a promising immunomodulator candidate for peptide-based human cancer vaccines, such as for the HLA-A2-restricted E7(11-20) epitope.",,"['Ding, Zhenzhen', 'Ou, Rongying', 'Ni, Bing', 'Tang, Jun', 'Xu, Yunsheng']",,,,
,PMC,Emerging & re-emerging infections in India: An overview,,PMC3767269,24056553,CC BY-NC-SA,"The incidence of emerging infectious diseases in humans has increased within the recent past or threatens to increase in the near future. Over 30 new infectious agents have been detected worldwide in the last three decades; 60 per cent of these are of zoonotic origin. Developing countries such as India suffer disproportionately from the burden of infectious diseases given the confluence of existing environmental, socio-economic, and demographic factors. In the recent past, India has seen outbreaks of eight organisms of emerging and re-emerging diseases in various parts of the country, six of these are of zoonotic origin. Prevention and control of emerging infectious diseases will increasingly require the application of sophisticated epidemiologic and molecular biologic technologies, changes in human behaviour, a national policy on early detection of and rapid response to emerging infections and a plan of action. WHO has made several recommendations for national response mechanisms. Many of these are in various stages of implementation in India. However, for a country of size and population of India, the emerging infections remain a real and present danger. A meaningful response must approach the problem at the systems level. A comprehensive national strategy on infectious diseases cutting across all relevant sectors with emphasis on strengthened surveillance, rapid response, partnership building and research to guide public policy is needed.",2013 Jul,"['Dikid, T.', 'Jain, S.K.', 'Sharma, A.', 'Kumar, A.', 'Narain, J.P.']",Indian J Med Res,,,
,PMC,Effect of Immunodeficiency on MPV Shedding and Transmission,,PMC3725932,,,"C57BL/6 (B6) mice briefly shed low levels of MPV, and transmission is inefficient. To determine whether deficits in B or T cells or in interferon γ on a B6 background increased the duration of MPV shedding or transmission, B-cell–deficient (Igh), interferon-γ–deficient (Ifnγ), B- and T-cell–deficient (Rag), and B6 mice were inoculated with MPV. At 1 and 2 wk postinoculation (wpi), 11% to 94% of mice shed MPV. From 4 to 18 wpi, 80% to 100% of Rag mice and 0% of B6 and Ifnγ mice shed MPV; Igh mice sporadically shed MPV through 20 wpi. MPV was transmitted from B6 mice and Ifnγ mice at 2 to 4 wpi. Rag and Igh mice transmitted MPV to sentinels at all or most time points, respectively, between 2 to 16 wpi. Once transmission ceased from B6, Ifnγ, and Igh mice, breeding trios were setup and showed that MPV was transmitted to offspring in only one cage of Igh mice. In another experiment, MPV shedding ceased from B6, CD8-deficient (CD8), CD4-deficient (CD4), and T-cell–receptor-deficient (TCR) mice by 2, 6, 8, and 8 wpi, respectively. MPV was transmitted to sentinels only at 1 to 4 wpi. Mesenteric lymph nodes collected from 61% to 100% of B6, Ifnγ, TCR, CD4, CD8, and Rag mice were MPV DNA-positive. In conclusion, MPV transmission did not differ between mice deficient in T cell functions or Ifnγ and B6 mice. In contrast, B-cell deficiency posed an increased risk for MPV transmission in mice.",,"['Macy, James D', 'Paturzo, Frank X', 'Compton, Susan R']",,,,
,PMC,Clinical Bovine Piroplasmosis Caused by Babesia occultans in Italy,http://dx.doi.org/10.1128/JCM.00713-13,PMC3697720,,,"A clinical outbreak of bovine piroplasmosis was reported in Italy. The etiological agent was characterized as Babesia occultans, a parasite regarded as apathogenic and never detected before in continental Europe. This report paves the way for further studies to assess the occurrence of this tick-transmitted protozoan in other European regions.",,"['Decaro, Nicola', 'Larocca, Vittorio', 'Parisi, Antonio', 'Losurdo, Michele', 'Lia, Riccardo Paolo', 'Greco, Maria Fiorella', 'Miccolis, Antonio', 'Ventrella, Gianpiero', 'Otranto, Domenico', 'Buonavoglia, Canio']",,,,
,PMC,Detection of Specific Antibodies against Tembusu Virus in Ducks by Use of an E Protein-Based Enzyme-Linked Immunosorbent Assay,http://dx.doi.org/10.1128/JCM.00361-13,PMC3697666,,,"We developed an enzyme-linked immunosorbent assay (ELISA) using eukaryotically expressed E protein as the antigen (termed E-ELISA) to detect antibodies to tembusu virus (TMUV) in ducks. The E-ELISA did not react with antisera to other known pathogens, indicating the E protein is specific for recognizing anti-TMUV antibodies. Compared to the serum neutralization test, the specificity and sensitivity of the E-ELISA was 93.2 and 97.8%, respectively. Therefore, this E-ELISA is a sensitive and rapid method for detecting antibodies against TMUV in ducks.",,"['Yin, Xiuchen', 'Lv, Rang', 'Chen, Xiaodan', 'Liu, Ming', 'Hua, Ronghong', 'Zhang, Yun']",,,,
,PMC,The papain-like protease of porcine epidemic diarrhea virus negatively regulates type I interferon pathway by acting as a viral deubiquitinase,http://dx.doi.org/10.1099/vir.0.051169-0,PMC4811637,,,"Porcine epidemic diarrhea virus (PEDV) is the cause of an economically important swine disease. Previous studies suggested that PEDV does not elicit a robust IFN response, but the mechanism(s) used to evade or block this innate immune response was not known. In this study, we found that PEDV infection blocked synthetic dsRNA-induced IFN-β production by interfering with the activation of interferon regulatory factor 3 (IRF3). We identified PEDV replicase encoded papain-like protease 2 (PLP2) as an IFN antagonist that depends on catalytic activity for its function. We show that levels of ubiquitinated proteins are reduced during PEDV infection and that PEDV PLP2 has deubiquitinase (DUB) activity that recognizes and processes both K-48 and K-63 linked polyubiquitin chains. Furthermore, we found that PEDV PLP2 strongly inhibits RIG-I- and STING-activated IFN expression and that PEDV PLP2 can be co-immunoprecipitated with and deubiquitinates RIG-I and STING, the key components of the signalling pathway for IFN expression. These results show that PEDV infection suppresses production of IFN-β and provides evidence indicating that the PEDV papain-like protease 2 acts as a viral DUB to interfere with the RIG-I- and STING-mediated signalling pathway.",,"['Xing, Yaling', 'Chen, Jianfei', 'Tu, Jian', 'Zhang, Bailing', 'Chen, Xiaojuan', 'Shi, Hongyan', 'Baker, Susan C.', 'Feng, Li', 'Chen, Zhongbin']",,,,
,PMC,The VP8* Domain of Neonatal Rotavirus Strain G10P[11] Binds to Type II Precursor Glycans,http://dx.doi.org/10.1128/JVI.03518-12,PMC3700318,,,"Naturally occurring bovine-human reassortant rotaviruses with a P[11] VP4 genotype exhibit a tropism for neonates. Interaction of the VP8* domain of the spike protein VP4 with sialic acid was thought to be the key mediator for rotavirus infectivity. However, recent studies have indicated a role for nonsialylated glycoconjugates, including histo-blood group antigens (HBGAs), in the infectivity of human rotaviruses. We sought to determine if the bovine rotavirus-derived VP8* of a reassortant neonatal G10P[11] virus interacts with hitherto uncharacterized glycans. In an array screen of >600 glycans, VP8* P[11] showed specific binding to glycans with the Galβ1-4GlcNAc motif, which forms the core structure of type II glycans and is the precursor of H type II HBGA. The specificity of glycan binding was confirmed through hemagglutination assays; GST-VP8* P[11] hemagglutinates type O, A, and B red blood cells as well as pooled umbilical cord blood erythrocytes. Further, G10P[11] infectivity was significantly enhanced by the expression of H type II HBGA in CHO cells. The bovine-origin VP4 was confirmed to be essential for this increased infectivity, using laboratory-derived reassortant viruses generated from sialic acid binding rotavirus SA11-4F and a bovine G10P[11] rotavirus, B223. The binding to a core glycan unit has not been reported for any rotavirus VP4. Core glycan synthesis is constitutive in most cell types, and modification of these glycans is thought to be developmentally regulated. These studies provide the first molecular basis for understanding neonatal rotavirus infections, indicating that glycan modification during neonatal development may mediate the age-restricted infectivity of neonatal viruses.",,"['Ramani, Sasirekha', 'Cortes-Penfield, Nicolas W.', 'Hu, Liya', 'Crawford, Sue E.', 'Czako, Rita', 'Smith, David F.', 'Kang, Gagandeep', 'Ramig, Robert F.', 'Le Pendu, Jacques', 'Prasad, B. V. Venkataram', 'Estes, Mary K.']",,,,
,PMC,"Identification of Multiple Novel Viruses, Including a Parvovirus and a Hepevirus, in Feces of Red Foxes",http://dx.doi.org/10.1128/JVI.00568-13,PMC3700315,,,"Red foxes (Vulpes vulpes) are the most widespread members of the order of Carnivora. Since they often live in (peri)urban areas, they are a potential reservoir of viruses that transmit from wildlife to humans or domestic animals. Here we evaluated the fecal viral microbiome of 13 red foxes by random PCR in combination with next-generation sequencing. Various novel viruses, including a parvovirus, bocavirus, adeno-associated virus, hepevirus, astroviruses, and picobirnaviruses, were identified.",,"['Bodewes, Rogier', 'van der Giessen, Joke', 'Haagmans, Bart L.', 'Osterhaus, Albert D. M. E.', 'Smits, Saskia L.']",,,,
,PMC,Monoclonal Antibodies Combined with Adenovirus-Vectored Interferon Significantly Extend the Treatment Window in Ebola Virus-Infected Guinea Pigs,http://dx.doi.org/10.1128/JVI.00173-13,PMC3700280,,,"Monoclonal antibodies (MAbs) are currently a promising treatment strategy against Ebola virus infection. This study combined MAbs with an adenovirus-vectored interferon (DEF201) to evaluate the efficacy in guinea pigs and extend the treatment window obtained with MAbs alone. Initiating the combination therapy at 3 days postinfection (d.p.i.) provided 100% survival, a significant improvement over survival with either treatment alone. The administration of DEF201 within 2 d.p.i. permits later MAb use, with protective efficacy observed up to 8 d.p.i.",,"['Qiu, Xiangguo', 'Wong, Gary', 'Fernando, Lisa', 'Ennis, Jane', 'Turner, Jeffrey D.', 'Alimonti, Judie B.', 'Yao, Xiaojian', 'Kobinger, Gary P.']",,,,
,PMC,Cellular Chaperonin CCTγ Contributes to Rabies Virus Replication during Infection,http://dx.doi.org/10.1128/JVI.03186-12,PMC3700271,,,"Rabies, as the oldest known infectious disease, remains a serious threat to public health worldwide. The eukaryotic cytosolic chaperonin TRiC/CCT complex facilitates the folding of proteins through ATP hydrolysis. Here, we investigated the expression, cellular localization, and function of neuronal CCTγ during neurotropic rabies virus (RABV) infection using mouse N2a cells as a model. Following RABV infection, 24 altered proteins were identified by using two-dimensional electrophoresis and mass spectrometry, including 20 upregulated proteins and 4 downregulated proteins. In mouse N2a cells infected with RABV or cotransfected with RABV genes encoding nucleoprotein (N) and phosphoprotein (P), confocal microscopy demonstrated that upregulated cellular CCTγ was colocalized with viral proteins N and P, which formed a hollow cricoid inclusion within the region around the nucleus. These inclusions, which correspond to Negri bodies (NBs), did not form in mouse N2a cells only expressing the viral protein N or P. Knockdown of CCTγ by lentivirus-mediated RNA interference led to significant inhibition of RABV replication. These results demonstrate that the complex consisting of viral proteins N and P recruits CCTγ to NBs and identify the chaperonin CCTγ as a host factor that facilitates intracellular RABV replication. This work illustrates how viruses can utilize cellular chaperonins and compartmentalization for their own benefit.",,"['Zhang, Jinyang', 'Wu, Xiaopeng', 'Zan, Jie', 'Wu, Yongping', 'Ye, Chengjin', 'Ruan, Xizhen', 'Zhou, Jiyong']",,,,
,PMC,The L60V Variation in Hepatitis B Virus Core Protein Elicits New Epitope-Specific Cytotoxic T Lymphocytes and Enhances Viral Replication,http://dx.doi.org/10.1128/JVI.00577-13,PMC3700222,,,"Mutations in the core protein (HBc) of hepatitis B virus (HBV) are associated with aggressive hepatitis and advanced liver diseases in chronic hepatitis B (CHB). In this study, we identified the L60V variation in HBc that generates a new HLA-A2-restricted CD8(+) T cell epitope by screening an overlapping 9-mer peptide pool covering HBc and its variants. The nonameric epitope V60 was determined by structural and immunogenic analysis. The HBc L60V variation is correlated with hepatic necroinflammation and higher viral levels, and it may be associated with a poor prognosis in CHB patients. Immunization with the defined HBV epitope V60 peptide elicited specific cytotoxic T lymphocyte (CTL)-induced liver injury in HLA-A2(+) HBV transgenic mice. In addition, in vitro and in vivo experiments both demonstrated that the HBc L60V variation facilitates viral capsid assembly and increases HBV replication. These data suggest that the HBc L60V variation can impact both HBV replication and HBV-specific T cell responses. Therefore, our work provides further dissection of the impact of the HBc L60V variation, which orchestrates HBV replication, viral persistence, and immunopathogenesis during chronic viral infection.",,"['Zhang, Yu', 'Ren, Yulin', 'Wu, Yan', 'Zhao, Bao', 'Qiu, Lipeng', 'Li, Xiaodong', 'Xu, Dongping', 'Liu, Jun', 'Gao, George F.', 'Meng, Songdong']",,,,
,PMC,Upregulation of CHOP/GADD153 during Coronavirus Infectious Bronchitis Virus Infection Modulates Apoptosis by Restricting Activation of the Extracellular Signal-Regulated Kinase Pathway,http://dx.doi.org/10.1128/JVI.00626-13,PMC3700216,,,"Induction of the unfolded protein response (UPR) is an adaptive cellular response to endoplasmic reticulum (ER) stress that allows a cell to reestablish ER homeostasis. However, under severe and persistent ER stress, prolonged UPR may activate unique pathways that lead to cell death. In this study, we investigated the activation of the protein kinase R-like ER kinase (PERK) pathway of UPR in cells infected with the coronavirus infectious bronchitis virus (IBV) and its relationship with IBV-induced apoptosis. The results showed moderate induction of PERK phosphorylation in IBV-infected cells. Meanwhile, activating transcription factor 4 (ATF4) was upregulated at the protein level in the infected cells, resulting in the induction in trans of the transcription factor ATF3 and the proapoptotic growth arrest and DNA damage-inducible protein GADD153. Knockdown of PERK by small interfering RNA (siRNA) suppressed the activation of GADD153 and the IBV-induced apoptosis. Interestingly, knockdown of protein kinase R (PKR) by siRNA and inhibition of the PKR kinase activity by 2-aminopurine (2-AP) also reduced the IBV-induced upregulation of GADD153 and apoptosis induction. In GADD153-knockdown cells, IBV-induced apoptosis was suppressed and virus replication inhibited, revealing a key role of GADD153 in IBV-induced cell death and virus replication. Analysis of the pathways downstream of GADD153 revealed much more activation of the extracellular signal-related kinase (ERK) pathway in GADD153-knockdown cells during IBV infection, indicating that GADD153 may modulate apoptosis through suppression of the pathway. This study provides solid evidence that induction of GADD153 by PERK and PKR plays an important regulatory role in the apoptotic process triggered by IBV infection.",,"['Liao, Ying', 'Fung, To Sing', 'Huang, Mei', 'Fang, Shou Guo', 'Zhong, Yanxin', 'Liu, Ding Xiang']",,,,
,PMC,The CD225 Domain of IFITM3 Is Required for both IFITM Protein Association and Inhibition of Influenza A Virus and Dengue Virus Replication,http://dx.doi.org/10.1128/JVI.00481-13,PMC3700195,,,"The interferon-induced transmembrane protein 3 (IFITM3) gene is an interferon-stimulated gene that inhibits the replication of multiple pathogenic viruses in vitro and in vivo. IFITM3 is a member of a large protein superfamily, whose members share a functionally undefined area of high amino acid conservation, the CD225 domain. We performed mutational analyses of IFITM3 and identified multiple residues within the CD225 domain, consisting of the first intramembrane domain (intramembrane domain 1 [IM1]) and a conserved intracellular loop (CIL), that are required for restriction of both influenza A virus (IAV) and dengue virus (DENV) infection in vitro. Two phenylalanines within IM1 (F75 and F78) also mediate a physical association between IFITM proteins, and the loss of this interaction decreases IFITM3-mediated restriction. By extension, similar IM1-mediated associations may contribute to the functions of additional members of the CD225 domain family. IFITM3's distal N-terminal domain is also needed for full antiviral activity, including a tyrosine (Y20), whose alteration results in mislocalization of a portion of IFITM3 to the cell periphery and surface. Comparative analyses demonstrate that similar molecular determinants are needed for IFITM3's restriction of both IAV and DENV. However, a portion of the CIL including Y99 and R87 is preferentially needed for inhibition of the orthomyxovirus. Several IFITM3 proteins engineered with rare single-nucleotide polymorphisms demonstrated reduced expression or mislocalization, and these events were associated with enhanced viral replication in vitro, suggesting that possessing such alleles may impact an individual's risk for viral infection. On the basis of this and other data, we propose a model for IFITM3-mediated restriction.",,"['John, Sinu P.', 'Chin, Christopher R.', 'Perreira, Jill M.', 'Feeley, Eric M.', 'Aker, Aaron M.', 'Savidis, George', 'Smith, Sarah E.', 'Elia, Andrew E. H.', 'Everitt, Aaron R.', 'Vora, Mehul', 'Pertel, Thomas', 'Elledge, Stephen J.', 'Kellam, Paul', 'Brass, Abraham L.']",,,,
,PMC,Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus Entry That Act by Three Distinct Mechanisms,http://dx.doi.org/10.1128/JVI.00998-13,PMC3700180,,,"Severe acute respiratory syndrome (SARS) is an infectious and highly contagious disease that is caused by SARS coronavirus (SARS-CoV) and for which there are currently no approved treatments. We report the discovery and characterization of small-molecule inhibitors of SARS-CoV replication that block viral entry by three different mechanisms. The compounds were discovered by screening a chemical library of compounds for blocking of entry of HIV-1 pseudotyped with SARS-CoV surface glycoprotein S (SARS-S) but not that of HIV-1 pseudotyped with vesicular stomatitis virus surface glycoprotein G (VSV-G). Studies on their mechanisms of action revealed that the compounds act by three distinct mechanisms: (i) SSAA09E2 {N-[[4-(4-methylpiperazin-1-yl)phenyl]methyl]-1,2-oxazole-5-carboxamide} acts through a novel mechanism of action, by blocking early interactions of SARS-S with the receptor for SARS-CoV, angiotensin converting enzyme 2 (ACE2); (ii) SSAA09E1 {[(Z)-1-thiophen-2-ylethylideneamino]thiourea} acts later, by blocking cathepsin L, a host protease required for processing of SARS-S during viral entry; and (iii) SSAA09E3 [N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)benzamide] also acts later and does not affect interactions of SARS-S with ACE2 or the enzymatic functions of cathepsin L but prevents fusion of the viral membrane with the host cellular membrane. Our work demonstrates that there are at least three independent strategies for blocking SARS-CoV entry, validates these mechanisms of inhibition, and introduces promising leads for the development of SARS therapeutics.",,"['Adedeji, Adeyemi O.', 'Severson, William', 'Jonsson, Colleen', 'Singh, Kamalendra', 'Weiss, Susan R.', 'Sarafianos, Stefan G.']",,,,
,PMC,Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Announcement of the Coronavirus Study Group,http://dx.doi.org/10.1128/JVI.01244-13,PMC3700179,,,,,"['de Groot, Raoul J.', 'Baker, Susan C.', 'Baric, Ralph S.', 'Brown, Caroline S.', 'Drosten, Christian', 'Enjuanes, Luis', 'Fouchier, Ron A. M.', 'Galiano, Monica', 'Gorbalenya, Alexander E.', 'Memish, Ziad A.', 'Perlman, Stanley', 'Poon, Leo L. M.', 'Snijder, Eric J.', 'Stephens, Gwen M.', 'Woo, Patrick C. Y.', 'Zaki, Ali M.', 'Zambon, Maria', 'Ziebuhr, John']",,,,
,PMC,H7N9 Influenza: The Emerging Infectious Disease,http://dx.doi.org/10.4103/1947-2714.115764,PMC3759064,24020046,CC BY-NC-SA,"Influenza virus infection is a common respiratory pathogen. Emerging of new atypical influenza is usually a big public health threat. H7N9 bird flu is the newest atypical influenza virus infection that has just been reported since early 2013. The emerging of this new disease occurred in China and becomes the present focus for possible worldwide pandemic. In this specific article, the author will discus and describe on epidemiology, symptomatology, pathology, diagnosis, treatment, and prevention of this new bird flu. The literature researching by PubMed and Google is used for data gathering in this collective review.",2013 Jul,"Wiwanitkit, Viroj",N Am J Med Sci,,,
,PMC,Resident viruses and their interactions with the immune system,http://dx.doi.org/10.1038/ni.2614,PMC3760236,,,"The human body is colonized with a diverse resident microflora that includes viruses. Recent studies of metagenomes have begun to characterize the composition of the human ‘virobiota’ and its associated genes (the ‘virome’), and have fostered the emerging field of host-virobiota interactions. In this Perspective, we explore how resident viruses interact with the immune system. We review recent findings that highlight the role of the immune system in shaping the composition of the virobiota and consider how resident viruses may impact host immunity. Finally, we discuss the implications of virobiota–immune system interactions for human health.",,"['Duerkop, Breck A', 'Hooper, Lora V']",,,,
,PMC,Regulation of hepatic innate immunity by hepatitis C virus,http://dx.doi.org/10.1038/nm.3253,PMC4251871,,,"Hepatitis C virus (HCV) is a global public health problem involving chronic infection of the liver in over 170 million people. Chronic HCV causes liver disease and is linked with liver cancer. Viral innate immune evasion strategies and human genetic determinants underlie the transition of acute HCV infection to viral persistence and the support of chronic infection. Host genetic factors, such as sequence polymorphisms in IFNL3, a gene in the host interferon system, can influence both the outcome of infection and response to antiviral therapy. Recent insights into how HCV regulates innate immune signaling within the liver reveal a complex interaction of patient genetic background with viral and host factors of innate immune triggering and control that impart the outcome of HCV infection and immunity.",,"['Horner, Stacy M.', 'Gale, Michael']",,,,
,PMC,The Struggle Against MERS-CoV (The Novel Coronavirus),http://dx.doi.org/10.5001/omj.2013.66,PMC3725253,,,,,"['Balkhair, Abdullah', 'Al Maamari, Khuloud', 'Alawi, Fatma Ba']",,,,
,PMC,Review on Sphaeranthus indicus Linn. (Koṭṭaikkarantai),http://dx.doi.org/10.4103/0973-7847.120517,PMC3841994,24347924,CC BY-NC-SA,"Sphaeranthus indicus Linn. is from the aroma family Asteraceae. It is also known with other synonyms such as Munditika, Mundi, Shravana, Bhikshu, Tapodhana, Mahashravani, Shravanahva, Shravanashirshaka. It is abundantly distributed in damp areas in plains and also as a weed in the rice fields. In the Indian system of medicine, the plant as a whole plant or its different anatomical parts viz., leaf, stem, bark, root, flower and seed are widely used for curing many diseases. The plant is bitter, stomachic, restorative, alterative, pectoral, demulcent and externally soothing. The whole plant and its anatomical parts have been reported with different types of secondary metabolites which include eudesmanolides, sesquiterpenoids, sesquiterpene lactones, sesquiterpene acids, flavone glycosides, flavonoid C-glycosides, isoflavone glycoside, sterols, sterol glycoside, alkaloid, peptide alkaloids, amino acids and sugars. The essential oils obtained from the flowers and whole plants were analyzed by different authors and reported the presence of many monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpene hydrocarbons and oxygenated sesquiterpenes. The whole plants, its isolated secondary metabolites and different anatomical parts have been reported for ovicidal, antifeedant, anthelmintic, antimicrobial, antiviral, macrofilaricidal, larvicidal, analgesic, antipyretic, hepatoprotective, antitussive, wound healing, bronchodilatory, mast cell stabilizing activity, anxiolytic, neuroleptic, immunomodulatory, anti-diabetic, antihyperlipidemic and antioxidant, antioxidant, central nervous system depressant, anti-arthritic, nephroprotective, anticonvulsant activities and many other activities. It is also effective on psoriasis. In the present paper, the plant is reviewed for its phytochemical and pharmacological reports in detail.",2013 Jul-Dec,"Ramachandran, Shakila",Pharmacogn Rev,,,
,PMC,Mammalian phosphatidylinositol 4-kinases as modulators of membrane trafficking and lipid signaling networks,http://dx.doi.org/10.1016/j.plipres.2013.04.002,PMC3989048,23608234,CC BY,"The four mammalian phosphatidylinositol 4-kinases modulate inter-organelle lipid trafficking, phosphoinositide signalling and intracellular vesicle trafficking. In addition to catalytic domains required for the synthesis of PI4P, the phosphatidylinositol 4-kinases also contain isoform-specific structural motifs that mediate interactions with proteins such as AP-3 and the E3 ubiquitin ligase Itch, and such structural differences determine isoform-specific roles in membrane trafficking. Moreover, different permutations of phosphatidylinositol 4-kinase isozymes may be required for a single cellular function such as occurs during distinct stages of GPCR signalling and in Golgi to lysosome trafficking. Phosphatidylinositol 4-kinases have recently been implicated in human disease. Emerging paradigms include increased phosphatidylinositol 4-kinase expression in some cancers, impaired functioning associated with neurological pathologies, the subversion of PI4P trafficking functions in bacterial infection and the activation of lipid kinase activity in viral disease. We discuss how the diverse and sometimes overlapping functions of the phosphatidylinositol 4-kinases present challenges for the design of isoform-specific inhibitors in a therapeutic context.",2013 Jul,"['Clayton, Emma L.', 'Minogue, Shane', 'Waugh, Mark G.']",Prog Lipid Res,,,
,PMC,Professor Fengcai Zhu: China leads the EV-71 vaccine research and development,http://dx.doi.org/10.3978/j.issn.2224-4336.2013.06.01,PMC4728927,,,,,"['Li, Ling', 'Li, Zhaorong', 'Chang, Xin']",,,,
,PMC,"Polymorphisms and Tissue Expression of the Feline Leukocyte Antigen Class I Loci FLAI-E, -H and -K",http://dx.doi.org/10.1007/s00251-013-0711-z,PMC3777221,,,"Cytotoxic CD8+ T-cell immunosurveillance for intracellular pathogens, such as viruses, is controlled by classical major histocompatibility complex (MHC) class Ia molecules, and ideally, these antiviral T-cell populations are defined by the specific peptide and restricting MHC allele. Surprisingly, despite the utility of the cat in modeling human viral immunity, little is known about the Feline Leukocyte Antigen class I complex (FLAI). Only a few coding sequences with uncertain locus origin and expression patterns have been reported. Of 19 class I genes, 3 loci - FLAI-E, -H and -K – are predicted to encode classical molecules, and our objective was to evaluate their status by analyzing polymorphisms and tissue expression. Using locus-specific, PCR-based genotyping, we amplified 33 FLAI-E, -H, and -K alleles from 12 cats of various breeds, identifying, for the first time, alleles across 3 distinct loci in a feline species. Alleles shared the expected polymorphic and invariant sites in the α1/α2 domains, and full-length cDNA clones possessed all characteristic class Ia exons. Alleles could be assigned to a specific locus with reasonable confidence, although there was evidence of potentially confounding interlocus recombination between FLAI-E and -K. Only FLAI-E, -H and -K-origin alleles were amplified from cDNAs of multiple tissue types. We also defined hypervariable regions across these genes, which permitted the assignment of names to both novel and established alleles. As predicted, FLAI-E, -H, and -K fulfill the major criteria of class Ia genes. These data represent a necessary prerequisite for studying epitope-specific antiviral CD8+ T-cell responses in cats.",,"['Holmes, Jennifer C.', 'Holmer, Savannah G.', 'Ross, Peter', 'Buntzman, Adam S.', 'Frelinger, Jeffrey A.', 'Hess, Paul R.']",,,,
,PMC,"Inhibitory and combinatorial effect of diphyllin, a v-ATPase blocker, on influenza viruses",http://dx.doi.org/10.1016/j.antiviral.2013.06.014,PMC3787953,,,"An influenza pandemic poses a serious threat to humans and animals. Conventional treatments against influenza include two classes of pathogen-targeting antivirals: M2 ion channel blockers (such as amantadine) and neuraminidase inhibitors (such as oseltamivir). Examination of the mechanism of influenza viral infection has shown that endosomal acidification plays a major role in facilitating the fusion between viral and endosomal membranes. This pathway has led to investigations on vacuolar ATPase (v-ATPase) activity, whose role as a regulating factor on influenza virus replication has been verified in extensive genome-wide screenings. Blocking v-ATPase activity thus presents the opportunity to interfere with influenza viral infection by preventing the pH-dependent membrane fusion between endosomes and virions. This study aims to apply diphyllin, a natural compound shown to be as a novel v-ATPase inhibitor, as a potential antiviral for various influenza virus strains using cell-based assays. The results show that diphyllin alters cellular susceptibility to influenza viruses through the inhibition of endosomal acidification, thus interfering with downstream virus replication, including that of known drug-resistant strains. In addition, combinatorial treatment of the host-targeting diphyllin with pathogen-targeting therapeutics (oseltamivir and amantadine) demonstrates enhanced antiviral effects and cell protection in vitro.",,"['Chen, Hui-Wen', 'Cheng, Jenna Xiao', 'Liu, Ming-Tsan', 'King, Kevin', 'Peng, Ju-Yi', 'Zhang, Xin-Quan', 'Wang, Ching-Ho', 'Shresta, Sujan', 'Schooley, Robert T.', 'Liu, Yu-Tsueng']",,,,
,PMC,"The C-type lectin receptor CLEC4M binds, internalizes, and clears von Willebrand factor and contributes to the variation in plasma von Willebrand factor levels",http://dx.doi.org/10.1182/blood-2012-10-457507,PMC3722568,,,"Genetic variation in or near the C-type lectin domain family 4 member M (CLEC4M) has been associated with plasma levels of von Willebrand factor (VWF) in healthy individuals. CLEC4M is a lectin receptor with a polymorphic extracellular neck region possessing a variable number of tandem repeats (VNTR). A total of 491 participants (318 patients with type 1 von Willebrand disease [VWD] and 173 unaffected family members) were genotyped for the CLEC4M VNTR polymorphism. Family-based association analysis on kindreds with type 1 VWD demonstrated an excess transmission of VNTR 6 to unaffected individuals (P = .0096) and an association of this allele with increased VWF:RCo (P = .029). CLEC4M-Fc bound to VWF. Immunofluorescence and enzyme-linked immunosorbent assay demonstrated that HEK 293 cells transfected with CLEC4M bound and internalized VWF. Cells expressing 4 or 9 copies of the CLEC4M neck region VNTR showed reduced interaction with VWF relative to CLEC4M with 7 VNTR (CLEC4M 4%-60% reduction, P < .001; CLEC4M 9%-45% reduction, P = .006). Mice expressing CLEC4M after hydrodynamic liver transfer have a 46% decrease in plasma levels of VWF (P = .0094). CLEC4M binds to and internalizes VWF, and polymorphisms in the CLEC4M gene contribute to variable plasma levels of VWF.",,"['Rydz, Natalia', 'Swystun, Laura L.', 'Notley, Colleen', 'Paterson, Andrew D.', 'Riches, J. Jacob', 'Sponagle, Kate', 'Boonyawat, Boonchai', 'Montgomery, Robert R.', 'James, Paula D.', 'Lillicrap, David']",,,,
,PMC,The need to include animal protection in public health policies,http://dx.doi.org/10.1057/jphp.2013.29,PMC3826830,23803712,CC BY,"Many critical public health issues require non-traditional approaches. Although many novel strategies are used, one approach not widely applied involves improving the treatment of animals. Emerging infectious diseases are pressing public health challenges that could benefit from improving the treatment of animals. Other human health issues, that overlap with animal treatment issues, and that warrant further exploration, are medical research and domestic violence. The diverse nature of these health issues and their connection with animal treatment suggest that there may be other similar intersections. Public health would benefit by including the treatment of animals as a topic of study and policy development.",2013 Nov 27,"Akhtar, Aysha",J Public Health Policy,,,
,PMC,Antigen-activated dendritic cells ameliorate influenza A infections,http://dx.doi.org/10.1172/JCI67550,PMC3696566,,,"Influenza A viruses cause significant morbidity and mortality worldwide. There is a need for alternative or adjunct therapies, as resistance to currently used antiviral drugs is emerging rapidly. We tested ligand epitope antigen presentation system (LEAPS) technology as a new immune-based treatment for influenza virus infection in a mouse model. Influenza-J-LEAPS peptides were synthesized by conjugating the binding ligand derived from the β2-microglobulin chain of the human MHC class I molecule (J-LEAPS) with 15 to 30 amino acid–long peptides derived from influenza virus NP, M, or HA proteins. DCs were stimulated with influenza-J-LEAPS peptides (influenza-J-LEAPS) and injected intravenously into infected mice. Antigen-specific LEAPS-stimulated DCs were effective in reducing influenza virus replication in the lungs and enhancing survival of infected animals. Additionally, they augmented influenza-specific T cell responses in the lungs and reduced the severity of disease by limiting excessive cytokine responses, which are known to contribute to morbidity and mortality following influenza virus infection. Our data demonstrate that influenza-J-LEAPS–pulsed DCs reduce virus replication in the lungs, enhance survival, and modulate the protective immune responses that eliminate the virus while preventing excessive cytokines that could injure the host. This approach shows promise as an adjunct to antiviral treatment of influenza virus infections.",,"['Boonnak, Kobporn', 'Vogel, Leatrice', 'Orandle, Marlene', 'Zimmerman, Daniel', 'Talor, Eyal', 'Subbarao, Kanta']",,,,
,PMC,Clinical severity of human infection with avian influenza A(H7N9) virus,http://dx.doi.org/10.1016/S0140-6736(13)61207-6,PMC3801178,,,"BACKGROUND: Characterizing the severity profile of human infections with influenza viruses of animal origin is a part of pandemic risk assessment, and an important part of the assessment of disease epidemiology. Our objective was to assess the clinical severity of human infections with the avian influenza A(H7N9) virus that has recently emerged in China. METHODS: Among laboratory-confirmed cases of A(H7N9) who were hospitalised, we estimated the risk of fatality, mechanical ventilation, and admission to the intensive care unit based on censored data during the currently ongoing outbreak. We also used information on laboratory-confirmed cases detected through sentinel influenza-like illness (ILI) surveillance to estimate the number of symptomatic A(H7N9) virus infections to date and the symptomatic case fatality risk. FINDINGS: Among 123 hospitalised cases, 37 cases had died and 69 had recovered by May 28, 2013. Hospitalised cases had high risks of mortality (36%; 95% confidence interval (CI): 26%–45%), mechanical ventilation or mortality (69%; 95% CI: 60%–77%), and ICU admission or mechanical ventilation or mortality (83%; 95% CI: 76%–90%), and the risk of these severe outcomes increased with age. Depending on assumptions about the coverage of the sentinel ILI network and health-care seeking behavior for cases of ILI associated with A(H7N9) virus infection, we estimated that the symptomatic case fatality risk could be between 160 and 2,800 per 100,000 symptomatic cases. INTERPRETATION: We estimated that the severity of A(H7N9) is somewhat lower than A(H5N1) but higher than seasonal influenza viruses and influenza A(H1N1)pdm09 virus. The estimated risks of fatality among hospitalised cases and symptomatic cases are measures of severity that should not be affected by shifts over time in the probability of laboratory-confirmation of mild cases and should inform risk assessment. FUNDING: Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special Administrative Region, China; and the US National Institutes of Health.",,"['Yu, Hongjie', 'Cowling, Benjamin J.', 'Feng, Luzhao', 'Lau, Eric H. Y.', 'Liao, Qiaohong', 'Tsang, Tim K.', 'Peng, Zhibin', 'Wu, Peng', 'Liu, Fengfeng', 'Fang, Vicky J.', 'Zhang, Honglong', 'Li, Ming', 'Zeng, Lingjia', 'Xu, Zhen', 'Li, Zhongjie', 'Luo, Huiming', 'Li, Qun', 'Feng, Zijian', 'Cao, Bin', 'Yang, Weizhong', 'Wu, Joseph T.', 'Wang, Yu', 'Leung, Gabriel M.']",,,,
,PMC,Comparative epidemiology of human infections with avian influenza A(H7N9) and A(H5N1) viruses in China,http://dx.doi.org/10.1016/S0140-6736(13)61171-X,PMC3777567,,,"BACKGROUND: The novel influenza A(H7N9) virus recently emerged, while influenza A(H5N1) virus has infected humans since 2003 in mainland China. Both infections are thought to be predominantly zoonotic. We compared the epidemiologic characteristics of the complete series of laboratory-confirmed cases of both viruses in mainland China to date. METHODS: An integrated database was constructed with information on demographic, epidemiological, and clinical variables of laboratory-confirmed A(H7N9) and A(H5N1) cases that were reported to the Chinese Center for Disease Control and Prevention up to May 24, 2013. We described disease occurrence by age, sex and geography and estimated key epidemiologic parameters. FINDINGS: Among 130 and 43 patients with confirmed A(H7N9) and A(H5N1) respectively, the median ages were 62y and 26y. In urban areas, 74% of cases of both viruses were male whereas in rural areas the proportions were 62% for A(H7N9) and 33% for A(H5N1). Among cases of A(H7N9) and A(H5N1), 75% and 71% reported recent exposure to poultry. The mean incubation periods of A(H7N9) and A(H5N1) were 3.1 and 3.3 days, respectively. On average, 21 and 18 contacts were traced for each A(H7N9) case in urban and rural areas respectively; compared to 90 and 63 for A(H5N1). The hospitalization fatality risk was 35% (95% CI: 25%, 44%) for A(H7N9) and 70% (95% CI: 56%, 83%) for A(H5N1). INTERPRETATION: The sex ratios in urban compared to rural cases are consistent with poultry exposure driving the risk of infection. However the difference in susceptibility to serious illness with the two different viruses remains unexplained, given that most A(H7N9) cases were in older adults while most A(H5N1) cases were in younger individuals. FUNDING: Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special Administrative Region, China; and the US National Institutes of Health.",,"['Cowling, Benjamin J.', 'Jin, Lianmei', 'Lau, Eric H. Y.', 'Liao, Qiaohong', 'Wu, Peng', 'Jiang, Hui', 'Tsang, Tim K.', 'Zheng, Jiandong', 'Fang, Vicky J.', 'Chang, Zhaorui', 'Ni, Michael Y.', 'Zhang, Qian', 'Ip, Dennis K. M.', 'Yu, Jianxing', 'Li, Yu', 'Wang, Liping', 'Tu, Wenxiao', 'Meng, Ling', 'Wu, Joseph T.', 'Luo, Huiming', 'Li, Qun', 'Shu, Yuelong', 'Li, Zhongjie', 'Feng, Zijian', 'Yang, Weizhong', 'Wang, Yu', 'Leung, Gabriel M.', 'Yu, Hongjie']",,,,
,PMC,Anchors Aweigh: Protein Traffic Mediated by Transmembrane Domains,http://dx.doi.org/10.1016/j.tcb.2013.05.005,PMC3783643,,,"The transmembrane domains (TMDs) of integral membrane proteins have emerged as major determinants of intracellular localization and transport in the secretory and endocytic pathways. Unlike sorting signals in the cytosolic domains, TMD sorting determinants are not conserved amino-acid sequences but physical properties such as length and hydrophilicity of the transmembrane span. The underlying sorting machinery is still poorly characterized but several mechanisms have been proposed, including TMD recognition by transmembrane sorting receptors and partitioning into membrane lipid domains. Here we review the nature of TMD sorting determinants and how they may dictate transmembrane protein localization and transport.",,"['Cosson, Pierre', 'Perrin, Jackie', 'Bonifacino, Juan S.']",,,,
,PMC,Synergistic Inhibitor Binding to the Papain-Like Protease of Human SARS Coronavirus – Mechanistic and Inhibitor Design Implications,http://dx.doi.org/10.1002/cmdc.201300134,PMC3954986,,,"We have previously developed two potent chemical classes that inhibit the essential papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus (SARS-CoV). In this study, we applied a novel approach to identify small fragments that act synergistically with these inhibitors. A fragment library was screened in combination with four previously developed lead inhibitors by fluorescence-based enzymatic assays. Several fragment compounds synergistically enhanced the inhibitory activity of the lead inhibitors by approximately an order of magnitude. Surface plasmon resonance (SPR) measurements showed that three fragments bind specifically to the PLpro enzyme. Mode of inhibition, computational solvent mapping, and molecular docking studies suggest that these fragments bind adjacent to the binding site of the lead inhibitors and further stabilize the inhibitor-bound state. We propose potential next generation compounds based upon a computational, fragment-merging approach. This approach provides an alternative strategy for lead optimization in cases where direct co-crystallization is difficult.",,"['Lee, Hyun', 'Cao, Shuyi', 'Hevener, Kirk E.', 'Truong, Lena', 'Gatuz, Joseph L.', 'Patel, Kavankumar', 'Ghosh, Arun K.', 'Johnson, Michael E.']",,,,
,PMC,Solution NMR Analyses of the C-type Carbohydrate Recognition Domain of DC-SIGNR Protein Reveal Different Binding Modes for HIV-derived Oligosaccharides and Smaller Glycan Fragments,http://dx.doi.org/10.1074/jbc.M113.458299,PMC3829359,,,"The C-type lectin DC-SIGNR (dendritic cell-specific ICAM-3-grabbing non-integrin-related; also known as L-SIGN or CD299) is a promising drug target due to its ability to promote infection and/or within-host survival of several dangerous pathogens (e.g. HIV and severe acute respiratory syndrome coronavirus (SARS)) via interactions with their surface glycans. Crystallography has provided excellent insight into the mechanism by which DC-SIGNR interacts with small glycans, such as (GlcNAc)(2)Man(3); however, direct observation of complexes with larger, physiological oligosaccharides, such as Man(9)GlcNAc(2), remains elusive. We have utilized solution-state nuclear magnetic resonance spectroscopy to investigate DC-SIGNR binding and herein report the first backbone assignment of its active, calcium-bound carbohydrate recognition domain. Direct interactions with the small sugar fragments Man(3), Man(5), and (GlcNAc)(2)Man(3) were investigated alongside Man(9)GlcNAc derived from recombinant gp120 (present on the HIV viral envelope), providing the first structural data for DC-SIGNR in complex with a virus-associated ligand, and unique binding modes were observed for each glycan. In particular, our data show that DC-SIGNR has a different binding mode for glycans on the HIV viral envelope compared with the smaller glycans previously observed in the crystalline state. This suggests that using the binding mode of Man(9)GlcNAc, instead of those of small glycans, may provide a platform for the design of DC-SIGNR inhibitors selective for high mannose glycans (like those on HIV). (15)N relaxation measurements provided the first information on the dynamics of the carbohydrate recognition domain, demonstrating that it is a highly flexible domain that undergoes ligand-induced conformational and dynamic changes that may explain the ability of DC-SIGNR to accommodate a range of glycans on viral surfaces.",,"['Probert, Fay', 'Whittaker, Sara B.-M.', 'Crispin, Max', 'Mitchell, Daniel A.', 'Dixon, Ann M.']",,,,
,PMC,Intranasal ipratropium bromide for the common cold,http://dx.doi.org/10.1002/14651858.CD008231.pub3,PMC6492479,,,"BACKGROUND: The common cold is one of the most common illnesses in humans and constitutes an economic burden both in terms of productivity and expenditure for treatment. There is no proven cure for the common cold and symptomatic relief is the mainstay of treatment. The use of intranasal ipratropium bromide (IB) has been addressed in several studies and might prove an effective treatment for the common cold. OBJECTIVES: To determine the effect of IB versus placebo or no treatment on severity of rhinorrhoea and nasal congestion in children and adults with the common cold. Subjective overall improvement was another primary outcome and side effects (for example, dry mucous membranes, epistaxis and systemic anticholinergic effects) were reported as a secondary outcome. SEARCH METHODS: In this updated review we searched CENTRAL 2013, Issue 3, MEDLINE (1950 to March week 4, 2013), MEDLINE in‐process and other non‐indexed citations (8 April 2013), EMBASE (1974 to April 2013), AMED (1985 to April 2013), Biosis (1974 to February 2011) and LILACS (1985 to April 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing IB to placebo or no treatment in children and adults with the common cold. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We used a standardised form to extract relevant data and we contacted trial authors for additional information. MAIN RESULTS: Seven trials with a total of 2144 participants were included. Four studies (1959 participants) addressed subjective change in severity of rhinorrhoea. All studies were consistent in reporting statistically significant changes in favour of IB. Nasal congestion was reported in four studies and was found to have no significant change between the two groups. Two studies found a positive response in the IB group for the global assessment of overall improvement. Side effects were more frequent in the IB group, odds ratio (OR) 2.09 (95% confidence interval (CI) 1.40 to 3.11). Commonly encountered side effects included nasal dryness, blood tinged mucus and epistaxis. The overall risk of bias in the included studies was moderate. AUTHORS' CONCLUSIONS: For people with the common cold, the existing evidence, which has some limitations, suggests that IB is likely to be effective in ameliorating rhinorrhoea. IB had no effect on nasal congestion and its use was associated with more side effects compared to placebo or no treatment although these appeared to be well tolerated and self limiting. There is a need for larger, high‐quality trials to determine the effectiveness of IB in relieving common cold symptoms.",,"['AlBalawi, Zaina H', 'Othman, Sahar S', 'AlFaleh, Khalid']",,,,
,PMC,Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1056/NEJMoa1306742,PMC4029105,,,"BACKGROUND: In September 2012, the World Health Organization reported the first cases of pneumonia caused by the novel Middle East respiratory syndrome coronavirus (MERS-CoV). We describe a cluster of health care–acquired MERS-CoV infections. METHODS: Medical records were reviewed for clinical and demographic information and determination of potential contacts and exposures. Case patients and contacts were interviewed. The incubation period and serial interval (the time between the successive onset of symptoms in a chain of transmission) were estimated. Viral RNA was sequenced. RESULTS: Between April 1 and May 23, 2013, a total of 23 cases of MERS-CoV infection were reported in the eastern province of Saudi Arabia. Symptoms included fever in 20 patients (87%), cough in 20 (87%), shortness of breath in 11 (48%), and gastrointestinal symptoms in 8 (35%); 20 patients (87%) presented with abnormal chest radiographs. As of June 12, a total of 15 patients (65%) had died, 6 (26%) had recovered, and 2 (9%) remained hospitalized. The median incubation period was 5.2 days (95% confidence interval [CI], 1.9 to 14.7), and the serial interval was 7.6 days (95% CI, 2.5 to 23.1). A total of 21 of the 23 cases were acquired by person-to-person transmission in hemodialysis units, intensive care units, or in-patient units in three different health care facilities. Sequencing data from four isolates revealed a single monophyletic clade. Among 217 household contacts and more than 200 health care worker contacts whom we identified, MERS-CoV infection developed in 5 family members (3 with laboratory-confirmed cases) and in 2 health care workers (both with laboratory-confirmed cases). CONCLUSIONS: Person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity. Surveillance and infection-control measures are critical to a global public health response.",,"['Assiri, Abdullah', 'McGeer, Allison', 'Perl, Trish M.', 'Price, Connie S.', 'Al Rabeeah, Abdullah A.', 'Cummings, Derek A.T.', 'Alabdullatif, Zaki N.', 'Assad, Maher', 'Almulhim, Abdulmohsen', 'Makhdoom, Hatem', 'Madani, Hossam', 'Alhakeem, Rafat', 'Al-Tawfiq, Jaffar A.', 'Cotten, Matthew', 'Watson, Simon J.', 'Kellam, Paul', 'Zumla, Alimuddin I.', 'Memish, Ziad A.']",,,,
,PMC,Reduced plasma ACE2 activity in dialysis patients: another piece in the conundrum of factors involved in hypertension and cardiovascular morbidity?,http://dx.doi.org/10.1093/ndt/gft240,PMC3769982,,,"the reduction in plasma ACE2 activity reported in ESRD patients treated by dialysis, particularly in female subjects, could limit Ang II degradation leading to increased levels of this peptide, which could contribute to the high prevalence of hypertension and cardiovascular morbidity that afflicts the dialysis population",,"['Wysocki, Jan', 'Batlle, Daniel']",,,,
,PMC,The Novel Replication-defective Vaccinia Virus (Tiantan Strain)–based Hepatitis C Virus Vaccine Induces Robust Immunity in Macaques,http://dx.doi.org/10.1038/mt.2013.122,PMC3776631,,,"The induction of a robust neutralizing antibody (nAb) response is likely to be as essential as specific cell-mediated immunity (CMI) against multiple antigens for the development of effective preventive and therapeutic vaccines against hepatitis C virus (HCV) infection in humans. To date, no data on the immunogenicity of the replication-defective vaccinia virus (derived from the Tiantan strain) (rNTV)-based HCV vaccine in primates have been reported. This study describes in detail the immunogenicity of various vaccine candidates in rhesus macaques, including rNTV-based and replication-defective recombinant adenoviral (rAd)–based HCV vaccines, as well as HCV pseudotyped virus-like particles (HCVpp). Our data showed that rAd-HCV vaccine boosting induced robust CMI, while priming or boosting with HCVpp enhanced the antigen-specific nAb response after rAd-HCV vaccination; however, CMI was not enhanced. Vaccination includes rNTV-HCV priming induced robust antigen-specific antibody, particularly nAbs, and CMI responses. Furthermore, more robust and longer-lasting CMI and higher cytokine levels (both Th1 and Th2 types, especially IFN-γ) resulted from boosting with rAd-HCV. We conclude that the rNTV-based HCV vaccine induces robust nAbs and CMI when combined with a heterogeneous primer-booster strategy, which shows promise for development of a human HCV vaccine.",,"['Wen, Bo', 'Deng, Yao', 'Chen, Hong', 'Guan, Jie', 'Chuai, Xia', 'Ruan, Li', 'Kong, Wei', 'Tan, Wenjie']",,,,
,PMC,"The Role of the Lung Microbiome in Health and Disease. A National Heart, Lung, and Blood Institute Workshop Report",http://dx.doi.org/10.1164/rccm.201303-0488WS,PMC5155250,,,"Study of the human lung microbiome in the context of pulmonary health and disease is an area of emerging research interest that is being driven by several contributing factors. These factors include increased recognition of the diversity of human-associated microbiota, their roles in health and in diseases associated with chronic inflammation, and advancements in technologies and tools that have facilitated such discoveries about the microbiota in organ systems outside of the lung. Therefore, the overarching goals of lung microbiome research are: to identify and characterize microbial populations associated with the respiratory tract and lungs; to understand their roles in lung health and disease; and, we hope, to allow the development of improved approaches for diagnosing and treating chronic respiratory diseases in which the microbiome has a role. Recent studies of the lung microbiome have yielded a number of interesting findings but also highlighted questions and challenges for researchers and clinicians. In December 2011, the National Heart, Lung, and Blood Institute convened a workshop to identify key issues and areas for further attention or development to advance research on the lung microbiome. Current knowledge and the state of research on the lung and related areas of human microbiome investigation were reviewed and discussed.",,"['Huang, Yvonne J.', 'Charlson, Emily S.', 'Collman, Ronald G.', 'Colombini-Hatch, Sandra', 'Martinez, Fernando D.', 'Senior, Robert M.']",,,,
,PMC,Intracellular processing of immunostimulatory CpG-siRNA: Toll-like receptor 9 facilitates siRNA dicing and endosomal escape,http://dx.doi.org/10.1016/j.jconrel.2013.06.007,PMC3742675,,,"Dicer-substrate siRNAs equipped with CpG oligodeoxyribonucleotides overcome the major hurdle in cell-specific siRNA delivery. The CpG-siRNA molecules are actively internalized by TLR9(+) cells, without the need for transfection reagents, leading to RNA interference both in vitro and in vivo. Here, we elucidate the molecular mechanisms of CpG-siRNA processing in target cells. We show that shortly after uptake into early endosomes (EE), CpG and siRNA parts of the conjugate are uncoupled in the presence of Dicer endonuclease. Diced siRNA molecules are translocated from endosomes to endoplasmic reticulum, where they can interact with the RNA interference machinery. We previously observed that even though TLR9 is not involved in CpG-siRNA uptake, it is indispensable for induction of gene silencing. To explain the role of TLR9 in intracellular processing of CpG-siRNA, we used primary macrophages derived from wild-type and Tlr9-deficient mice. Macrophages lacking TLR9 showed extended endosomal colocalization of CpG and siRNA parts of the conjugate. However, Tlr9 ablation did not interfere with the interaction of CpG-siRNA with Dicer as shown by in situ proximity ligation assay. Using CpG-siRNA labeled with pH-sensitive dye, we finally identified that lack of TLR9 in macrophages resulted in significant retention of the siRNA in endosomes. Thus, TLR9 facilitates the critical step following CpG-siRNA uncoupling, which is cytoplasmic release of the diced siRNA. These findings suggest that the class of immunostimulatory siRNAs may benefit from activation of certain endosomal immune receptors, such as TLR9, in augmented gene silencing and therapeutic efficacy.",,"['Nechaev, Sergey', 'Gao, Chan', 'Moreira, Dayson', 'Swiderski, Piotr', 'Jozwiak, Agnieszka', 'Kowolik, Claudia M.', 'Zhou, Jiehua', 'Armstrong, Brian', 'Raubitschek, Andrew', 'Rossi, John J.', 'Kortylewski, Marcin']",,,,
,PMC,IL‐4 induces a suppressive IL‐10‐producing CD8(+) T cell population via a Cdkn2a‐dependent mechanism,http://dx.doi.org/10.1189/jlb.0213064,PMC6607996,,,"CD8(+) T cells play an important role in immune regulation and effective immune responses against tumor cells, viral infection, and intracellular pathogens. In this report, using tiger or 10BiT mice, we defined a population of IL‐10‐producing CD8(+) T cells that were induced by IL‐4. These IL‐10(+)CD8(+) T cells possessed a strong inhibitory effect on the CD4(+) T cell proliferation in an IL‐10‐dependent and cell contact‐dependent fashion. In comparison with IL‐10(−)CD8(+) T cells, IL‐10(+)CD8(+) T cells expressed an array of Th2‐like cytokines (IL‐4, IL‐5), perforin, and granzymes, as well as the cell cycle regulatory protein Cdkn2a. Interestingly, knockdown of cdkn2a using siRNA reduced IL‐4‐induced IL‐10 production significantly. Furthermore, CD8(+) T cells from Cdkn2a(−/−) mice produced a significantly lower amount of IL‐10, and the effect was limited to CD8(+) T cells but not observed in CD4(+) T cells and APCs. Finally, IL‐10(+)CD8(+) T cells played a protective role in the TNBS‐induced murine colitis model, indicating a critical role of this population of CD8(+) T cells in regulatory immune responses. Taken together, we have defined a population of IL‐10‐producing CD8(+) Tregs induced by IL‐4 and mediated by Cdkn2a.",,"['Zhao, Yapu', 'Zhao, Huiyuan', 'Sun, Yuehong', 'Hao, Jianlei', 'Qi, Xiaofei', 'Zhou, Xinglong', 'Wu, Zhenzhou', 'Wang, Puyue', 'Kaech, Susan M.', 'Weaver, Casey T.', 'Flavell, Richard A.', 'Zhao, Liqing', 'Yao, Zhi', 'Yin, Zhinan']",,,,
,PMC,Analytical use of multi-protein fluorescence resonance energy transfer to demonstrate membrane-facilitated interactions within cytokine receptor complexes,http://dx.doi.org/10.1016/j.cyto.2013.05.008,PMC3770794,,,"Experiments measuring Fluorescence Resonance Energy Transfer (FRET) between cytokine receptor chains and their associated proteins led to hypotheses describing their organization in intact cells. These interactions occur within a larger protein complex or within a given nano-environment. To illustrate this complexity empirically, we developed a protocol to analyze FRET among more than two fluorescent proteins (multi-FRET). In multi-FRET, we model FRET among more than two fluorophores as the sum of all possible pairwise interactions within the complex. We validated our assumption by demonstrating that FRET among pairs within a fluorescent triplet resembled FRET between each pair measured in the absence of the third fluorophore. FRET between two receptor chains increases with increasing FRET between the ligand-binding chain (e.g., IFN-γR1, IL-10R1 and IFN-λR1) and an acylated fluorescent protein that preferentially resides within subsections of the plasma membrane. The interaction of IL-10R2 with IFN-λR1 or IL-10R1 results in decreased FRET between IL-10R2 and the acylated fluorescent protein. Finally, we analyzed FRET among four fluorescent proteins to demonstrate that as FRET between IFN-γR1 and IFN-γR2 or between IFN-αR1 and IFN-αR2c increases, FRET among other pairs of proteins changes within each complex.",,"['Krause, Christopher D.', 'Izotova, Lara S.', 'Pestka, Sidney']",,,,
,PMC,Transmission scenarios for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and how to tell them apart,,PMC4088931,,,"Detection of human cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection internationally is a global public health concern. Rigorous risk assessment is particularly challenging in a context where surveillance may be subject to under-ascertainment and a selection bias towards more severe cases. We would like to assess whether the virus is capable of causing widespread human epidemics, and whether self-sustaining transmission is already under way. Here we review possible transmission scenarios for MERS-CoV and their implications for risk assessment and control. We discuss how existing data, future investigations and analyses may help in reducing uncertainty and refining the public health risk assessment and present analytical approaches that allow robust assessment of epidemiological characteristics, even from partial and biased surveillance data. Finally, we urge that adequate data be collected on future cases to permit rigorous assessment of the transmission characteristics and severity of MERS-CoV, and the public health threat it may pose. Going beyond minimal case reporting, open international collaboration, under the guidance of the World Health Organization and the International Health Regulations, will impact on how this potential epidemic unfolds and prospects for control.",,"['Cauchemez, S', 'Van Kerkhove, M D', 'Riley, S', 'Donnelly, C A', 'Fraser, C', 'Ferguson, N M']",,,,
,PMC,Regulation of urinary ACE2 in diabetic mice,http://dx.doi.org/10.1152/ajprenal.00600.2012,PMC3891267,,,"Angiotensin-converting enzyme-2 (ACE2) enhances the degradation of ANG II and its expression is altered in diabetic kidneys, but the regulation of this enzyme in the urine is unknown. Urinary ACE2 was studied in the db/db model of type 2 diabetes and stretozotocin (STZ)-induced type 1 diabetes during several physiological and pharmacological interventions. ACE2 activity in db/db mice was increased in the serum and to a much greater extent in the urine compared with db/m controls. Neither a specific ANG II blocker, telmisartan, nor an ACE inhibitor, captopril, altered the levels of urinary ACE2 in db/db or db/m control mice. High-salt diet (8%) increased whereas low-salt diet (0.1%) decreased urinary ACE2 activity in the urine of db/db mice. In STZ mice, urinary ACE2 was also increased, and insulin decreased it partly but significantly after several weeks of administration. The increase in urinary ACE2 activity in db/db mice reflected an increase in enzymatically active protein with two bands identified of molecular size at 110 and 75 kDa and was associated with an increase in kidney cortex ACE2 protein at 110 kDa but not at 75 kDa. ACE2 activity was increased in isolated tubular preparations but not in glomeruli from db/db mice. Administration of soluble recombinant ACE2 to db/m and db/db mice resulted in a marked increase in serum ACE2 activity, but no gain in ACE2 activity was detectable in the urine, further demonstrating that urinary ACE2 is of kidney origin. Increased urinary ACE2 was associated with more efficient degradation of exogenous ANG II (10(−9) M) in urine from db/db compared with that from db/m mice. Urinary ACE2 could be a potential biomarker of increased metabolism of ANG II in diabetic kidney disease.",,"['Wysocki, Jan', 'Garcia-Halpin, Laura', 'Ye, Minghao', 'Maier, Christoph', 'Sowers, Kurt', 'Burns, Kevin D.', 'Batlle, Daniel']",,,,
,PMC,CD13 is essential for inflammatory trafficking and infarct healing following permanent coronary artery occlusion in mice,http://dx.doi.org/10.1093/cvr/cvt155,PMC3778957,,,"AIMS: To determine the role of CD13 as an adhesion molecule in trafficking of inflammatory cells to the site of injury in vivo and its function in wound healing following myocardial infarction induced by permanent coronary artery occlusion. METHODS AND RESULTS: Seven days post-permanent ligation, hearts from CD13 knockout (CD13(KO)) mice showed significant reductions in cardiac function, suggesting impaired healing in the absence of CD13. Mechanistically, CD13(KO) infarcts showed an increase in small, endothelial-lined luminal structures, but no increase in perfusion, arguing against an angiogenic defect in the absence of CD13. Cardiac myocytes of CD13(KO) mice showed normal basal contractile function, eliminating myocyte dysfunction as a mechanism of adverse remodelling. Conversely, immunohistochemical and flow cytometric analysis of CD13(KO) infarcts demonstrated a dramatic 65% reduction in infiltrating haematopoietic cells, including monocytes, macrophages, dendritic, and T cells, suggesting a critical role for CD13 adhesion in inflammatory trafficking. Accordingly, CD13(KO) infarcts also contained fewer myofibroblasts, consistent with attenuation of fibroblast differentiation resulting from the reduced inflammation, leading to adverse remodelling. CONCLUSION: In the ischaemic heart, while compensatory mechanisms apparently relieve potential angiogenic defects, CD13 is essential for proper trafficking of the inflammatory cells necessary to prime and sustain the reparative response, thus promoting optimal post-infarction healing.",,"['Pereira, Flavia E.', 'Cronin, Chunxia', 'Ghosh, Mallika', 'Zhou, Si-Yuan', 'Agosto, Mariela', 'Subramani, Jaganathan', 'Wang, Ruibo', 'Shen, Jian-Bing', 'Schacke, Wolfgang', 'Liang, Brannen', 'Yang, Tie Hong', 'McAulliffe, Beata', 'Liang, Bruce T.', 'Shapiro, Linda H.']",,,,
,PMC,More than 100 countries still not using global outbreak surveillance regulations,http://dx.doi.org/10.1503/cmaj.109-4479,PMC3680584,,,,,"Brown, Carolyn",,,,
,PMC,Stress Proteins in Aging and Life Span,http://dx.doi.org/10.3109/02656736.2013.798873,PMC4083487,,,"Heat shock proteins (HSP) are molecular chaperones and have been implicated in longevity and aging in many species. Their major functions include, chaperoning misfolded or newly synthesized polypeptides, protecting cells from proteotoxic stress, and processing of immunogenic agents. These proteins are expressed constitutively and can be induced by stresses such as heat, oxidative stress and many more. The induction of HSP in aging could potentially maintain protein homeostasis and longevity by refolding the damaged proteins which accumulate during aging and are toxic to cells. HSP are shown to increase life span in model organisms such as C. elegans and decrease aging related proteotoxicity. Thus, decrease in HSP in aging is associated with disruption of cellular homeostasis which causes diseases such as cancer, cell senescence and neurodegeneration. HSP levels are decreased with aging in most organs including neurons. Aging also causes attenuation or alteration of many signaling pathways as well as the expression of transcription factors such as heat shock factor (HSF). The alteration in regulation and synthesis of Forkhead box O3a (FOXO3a) family of transcription factors as well as major antioxidant enzymes [manganese superoxide dismutase (MnSOD), catalase] are also seen in aging. Among many signaling mechanisms involved in altering longevity and aging, the insulin/IGF1 pathway and the Sir2 deacetylase are highly significant. This review inquires into the role of some of these pathways in longevity/aging along with HSP.",,"['Murshid, Ayesha', 'Eguchi, Takanori', 'Calderwood, Stuart K.']",,,,
,PMC,"In HIV/hepatitis C virus co-infected patients, higher 25-hydroxyvitamin D concentrations were not related to hepatitis C virus treatment responses but were associated with ritonavir use(1)(2)(3)(4)",http://dx.doi.org/10.3945/ajcn.112.048785,PMC3712551,,,"Background: Among patients with hepatitis C virus (HCV) monoinfection, 25-hydroxyvitamin D [25(OH)D] concentrations are positively associated with a response to peg-interferon/ribavirin. Data on the relation between 25(OH)D concentrations and HCV treatment response in HIV-infected patients are limited. Objective: The objective was to determine whether baseline 25(OH)D concentrations predict virologic response in HIV/HCV co-infected patients and to examine variables associated with 25(OH)D concentrations ≥30 ng/mL. Design: Data and samples from 144 HCV genotype 1, treatment-naive patients from a completed HCV treatment trial were examined in this retrospective study. Early virologic response (EVR) was defined as ≥2 log(10) reduction in HCV RNA and/or HCV RNA <600 IU/mL at week 12 of peg-interferon/ribavirin treatment. Baseline 25(OH)D was measured by liquid chromatography/tandem mass spectrometry. Results: Compared with the non-EVR control group (n = 68), the EVR group (n = 76) was younger, had fewer cirrhotic subjects, had a higher proportion with the IL28B CC genotype, had a higher albumin concentration, and had a lower HCV viral load at baseline (P ≤ 0.05). The difference in baseline 25(OH)D concentrations between EVR and non-EVR patients was not statistically significant (median: 25 ng/mL compared with 20 ng/mL; P = 0.23). Similar results were found for sustained virologic response (SVR). In multivariable analysis, white and Hispanic race-ethnicity (OR: 6.26; 95% CI: 2.47, 15.88; P = 0.0001) and ritonavir use (OR: 2.68; 95% CI: 1.08, 6.65; P = 0.033) were associated with higher 25(OH)D concentrations (≥30 ng/mL). Conclusion: Baseline 25(OH)D concentrations did not predict EVR or SVR. Because ritonavir impairs the conversion of 25(OH)D to the active metabolite, utilization of 25(OH)D may have been impaired in subjects taking ritonavir. This trial was registered at www.clinicaltrials.gov as NCT00078403.",,"['Branch, Andrea D', 'Kang, Minhee', 'Hollabaugh, Kimberly', 'Wyatt, Christina M', 'Chung, Raymond T', 'Glesby, Marshall J']",,,,
,PMC,Emmprin and KSHV: new partners in viral cancer pathogenesis,http://dx.doi.org/10.1016/j.canlet.2013.05.037,PMC3728473,,,"Emmprin (CD147; basigin) is a multifunctional glycoprotein expressed at higher levels by cancer cells and stromal cells in the tumor microenvironment. Through direct effects within tumor cells and promotion of tumor-stroma interactions, emmprin participates in induction of tumor cell invasiveness, angiogenesis, metastasis and chemoresistance. Although its contribution to cancer progression has been widely studied, the role of emmprin in viral oncogenesis still remains largely unclear, and only a small body of available literature implicates emmprin-associated mechanisms in viral pathogenesis and tumorigenesis. We summarize these data in this review, focusing on the role of emmprin in pathogenesis associated with the Kaposi sarcoma-associated herpesvirus (KSHV), a common etiology for cancers arising in the setting of immune suppression. We also discuss future directions for mechanistic studies exploring roles for emmprin in viral cancer pathogenesis.",,"['Dai, Lu', 'Bai, Lihua', 'Lu, Ying', 'Xu, Zengguang', 'Reiss, Krys', 'Valle, Luis Del', 'Kaleeba, Johnan', 'Toole, Bryan P.', 'Parsons, Chris', 'Qin, Zhiqiang']",,,,
,PMC,SYSTEMS VIROLOGY: HOST-DIRECTED APPROACHES TO VIRAL PATHOGENESIS AND DRUG TARGETING,http://dx.doi.org/10.1038/nrmicro3036,PMC4028060,,,"High-throughput molecular profiling and computational biology are changing the face of virology, providing a new appreciation of the importance of the host in viral pathogenesis and offering unprecedented opportunities for better diagnostics, therapeutics and vaccines. Here, we provide a snapshot of the evolution of systems virology, from global gene expression profiling and signatures of disease outcome, to geometry-based computational methods that promise to yield novel therapeutic targets, personalized medicine and adeeper understanding of how viruses cause disease. To realize these goals, pipets and petri dishes need to join forces with the powers of mathematics and computational biology.",,"['Law, G. Lynn', 'Korth, Marcus J.', 'Benecke, Arndt G.', 'Katze, Michael G.']",,,,
,PMC,Inhibition of multiplication of the prototypic arenavirus LCMV by valproic acid,http://dx.doi.org/10.1016/j.antiviral.2013.05.012,PMC3733796,,,"Valproic acid (VPA), a short chain fatty acid commonly used for treatment of neurological disorders, has been shown to inhibit production of infectious progeny of different enveloped viruses including the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). In this study we have investigated the mechanisms by which VPA inhibits LCMV multiplication in cultured cells. VPA reduced production of infectious LCMV progeny and virus propagation without exerting a major blockage on either viral RNA or protein synthesis, but rather affecting the cell release and specific infectivity of LCMV progeny from infected cells. Our results would support the repurposing of VPA as a candidate antiviral drug to combat arenavirus infections.",,"['Vázquez-Calvo, Ángela', 'Martín-Acebes, Miguel A.', 'Sáiz, Juan-Carlos', 'Ngo, Nhi', 'Sobrino, F.', 'de la Torre, Juan Carlos']",,,,
,PMC,The emergence and diversification of panzootic H5N1 influenza viruses,http://dx.doi.org/10.1016/j.virusres.2013.05.012,PMC4017639,,,"The Asian highly pathogenic avian influenza H5N1 virus was first detected in the goose population of Guangdong, China in 1996. The viruses in this lineage are unique in their ecological success, demonstrating an extremely broad host range and becoming established in poultry over much of Asia and in Africa. H5N1 viruses have also diverged into multiple clades and subclades that generally do not cross neutralize, which has greatly confounded control measures in poultry and pre-pandemic vaccine strain selection. Although H5N1 viruses currently cannot transmit efficiently between mammals they exhibit high mortality in humans and recent experimental studies have shown that it is possible to generate an H5N1 virus that is transmissible in mammals. In addition to causing unprecedented economic losses, the long-term presence of the H5N1 virus in poultry and its frequent introductions to humans continue to pose a significant pandemic threat. Here we provide a summary of the genesis, molecular epidemiology and evolution of this H5N1 lineage, particularly the factors that have contributed to the continued diversification and ecological success of H5N1 viruses, with particular reference to the poultry production systems they have emerged from.",,"['Guan, Yi', 'Smith, Gavin J.D.']",,,,
,PMC,Global analysis of differential expressed genes in ECV304 Endothelial-like cells infected with human cytomegalovirus,http://dx.doi.org/10.4314/ahs.v13i2.6,PMC3824489,,,"BACKGROUND: Human cytomegalovirus (HCMV) is a virus which has the potential to alter cellular gene expression through multiple mechanisms. OBJECTIVE: With the application of DNA microarrays, we could monitor the effects of pathogens on host-cell gene expression programmes in great depth and on a broad scale. METHODS: Changes in mRNA expression levels of human endothelial-like ECV304 cells following infection with human cytomegalovirus AD169 strain was analyzed by a microarray system comprising 21073 60-mer oligonucleotide probes which represent 18716 human genes or transcripts. RESULTS: The results from cDNA microarray showed that there were 559 differential expressed genes consisted of 471 upregulated genes and 88 down-regulated genes. Real-time qPCR was performed to validate the expression of 6 selected genes (RPS24, MGC8721, SLC27A3, MST4, TRAF2 and LRRC28), and the results of which were consistent with those from the microarray. Among 237 biology processes, 39 biology processes were found to be related significantly to HCMV-infection. The signal transduction is the most significant biological process with the lowest p value (p=0.005) among all biological process which involved in response to HCMV infection. CONCLUSION: Several of these gene products might play key roles in virus-induced pathogenesis. These findings may help to elucidate the pathogenic mechanisms of HCMV caused diseases.",,"['Xiaoyang, Mo', 'Haiquan, Z', 'Huanying, Z', 'Changwen, K', 'Wenling, Z', 'Yanyang, Tu', 'Yongsheng, Z']",,,,
,PMC,Innate Immune Response of Human Alveolar Type II Cells Infected with Severe Acute Respiratory Syndrome–Coronavirus,http://dx.doi.org/10.1165/rcmb.2012-0339OC,PMC3727876,,,"Severe acute respiratory syndrome (SARS)–coronavirus (CoV) produces a devastating primary viral pneumonia with diffuse alveolar damage and a marked increase in circulating cytokines. One of the major cell types to be infected is the alveolar type II cell. However, the innate immune response of primary human alveolar epithelial cells infected with SARS-CoV has not been defined. Our objectives included developing a culture system permissive for SARS-CoV infection in primary human type II cells and defining their innate immune response. Culturing primary human alveolar type II cells at an air–liquid interface (A/L) improved their differentiation and greatly increased their susceptibility to infection, allowing us to define their primary interferon and chemokine responses. Viral antigens were detected in the cytoplasm of infected type II cells, electron micrographs demonstrated secretory vesicles filled with virions, virus RNA concentrations increased with time, and infectious virions were released by exocytosis from the apical surface of polarized type II cells. A marked increase was evident in the mRNA concentrations of interferon–β and interferon–λ (IL-29) and in a large number of proinflammatory cytokines and chemokines. A surprising finding involved the variability of expression of angiotensin-converting enzyme–2, the SARS-CoV receptor, in type II cells from different donors. In conclusion, the cultivation of alveolar type II cells at an air–liquid interface provides primary cultures in which to study the pulmonary innate immune responses to infection with SARS-CoV, and to explore possible therapeutic approaches to modulating these innate immune responses.",,"['Qian, Zhaohui', 'Travanty, Emily A.', 'Oko, Lauren', 'Edeen, Karen', 'Berglund, Andrew', 'Wang, Jieru', 'Ito, Yoko', 'Holmes, Kathryn V.', 'Mason, Robert J.']",,,,
,PMC,"RACE, GENDER AND TOTAL KNEE REPLACEMENT CONSIDERATION: THE ROLE OF SOCIAL SUPPORT",http://dx.doi.org/10.1002/acr.21926,PMC3619024,,,"OBJECTIVE: To determine whether there are racial differences in social support among patients with knee osteoarthritis (OA) and whether the impact of social support on patient preferences for total knee replacement (TKR) varies by race and gender. METHODS: 514 white & 285 African-American (AA) patients with knee OA were surveyed. Logistic regression models were performed to determine if the relationship between willingness to undergo TKR and the interaction of patient race and sex were mediated by social support. RESULTS: Compared to whites with knee OA, AA patients were less likely to be married (p<0.001), reported less close friends/relatives (p<0.001) and had lower Medical Outcomes Study-Social Support Scale (MOS-SSS) scores (p<0.001). AA patients were also less willing to undergo TKR (62% vs. 80%, p<0.001) than whites. The odds of willingness to undergo TKR was less in white females compared to white males when adjusted for recruitment site, age, income and WOMAC (OR 0.57, 95% CI 0.34–0.96). This difference was no longer significant when further adjusted for marital status, number of close friends/relatives and MOS-SSS score, but the effect size remained unchanged (OR 0.60, 95% CI 0.35–1.02). The odds of willingness to undergo TKR remained much less in AA females (OR 0.35, 95% CI 0.19–0.64) and AA males (OR 0.28, 95% CI 0.14–0.54) compared to white males when controlled for sociodemographic, clinical and social support measures. CONCLUSIONS: AA patients reported less structural and functional social support than whites. Social support is an important determinant of preference for TKR surgery only among whites.",,"['Vina, Ernest R.', 'Cloonan, Yona K.', 'Ibrahim, Said A.', 'Hannon, Michael J.', 'Boudreau, Robert M.', 'Kwoh, C. Kent']",,,,
,PMC,Differentiating Microbial Forensic qPCR Target and Control Products by Electrospray Ionization Mass Spectrometry,http://dx.doi.org/10.1089/bsp.2012.0062,PMC3696942,,,"Molecular bioforensic research is dependent on rapid and sensitive methods such as real-time PCR (qPCR) for the identification of microorganisms. The use of synthetic positive control templates containing small modifications outside the primer and probe regions is essential to ensure all aspects of the assay are functioning properly, including the primers and probes. However, a typical qPCR or reverse transcriptase qPCR (qRT-PCR) assay is limited in differentiating products generated from positive controls and biological samples because the fluorescent probe signals generated from each type of amplicon are indistinguishable. Additional methods used to differentiate amplicons, including melt curves, secondary probes, and amplicon sequencing, require significant time to implement and validate and present technical challenges that limit their use for microbial forensic applications. To solve this problem, we have developed a novel application of electrospray ionization mass spectrometry (ESI-MS) to rapidly differentiate qPCR amplicons generated with positive biological samples from those generated with synthetic positive controls. The method has sensitivity equivalent to qPCR and supports the confident and timely determination of the presence of a biothreat agent that is crucial for policymakers and law enforcement. Additionally, it eliminates the need for time-consuming methods to confirm qPCR results, including development and validation of secondary probes or sequencing of small amplicons. In this study, we demonstrate the effectiveness of this approach with microbial forensic qPCR assays targeting multiple biodefense agents (bacterial, viral, and toxin) for the ability to rapidly discriminate between a positive control and a positive sample.",,"['Motley, S. Timothy', 'Redden, Cassie L.', 'Sannes-Lowery, Kristin A.', 'Eshoo, Mark W.', 'Hofstadler, Steven A.', 'Burans, James P.', 'Rosovitz, M. J.']",,,,
,PMC,"Survey of western Canadian beef producers regarding calf-hood diseases, management practices, and veterinary service usage",,PMC3659451,,,"Cow-calf producers in western Canada were surveyed in June 2010 regarding calf-hood diseases and veterinary service usage; 310 producers responded. Use of veterinary services, particularly herd-health related services, increased with herd size as did neonatal diarrhea and clostridial vaccine usage. Administration of clostridial vaccines to pregnant dams before calving was associated with a reduction in neonatal diarrhea treatments; however, there was no association between neonatal diarrhea vaccine usage and a reduction in diarrhea treatments. Producers with > 220 breeding females were more likely than those with < 85 breeding females to seek veterinary advice regarding treating sick calves, have a veterinarian necropsy dead calves, have a veterinarian pregnancy check their bred females, and evaluate their herd bulls for breeding soundness.",,"['Waldner, Cheryl', 'Jelinski, Murray D.', 'McIntyre-Zimmer, Katelyn']",,,,
,PMC,Pre-clinical toxicity & immunobiological evaluation of DNA rabies vaccine & combination rabies vaccine in rhesus monkeys (Macaca mulatta),,PMC3734712,23852288,CC BY-NC-SA,"BACKGROUND & OBJECTIVES: Pre-clinical toxicology evaluation of biotechnology products is a challenge to the toxicologist. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed recombinant DNA anti-rabies vaccine [DRV (100 μg)] and combination rabies vaccine [CRV (100 μg DRV and 1.25 IU of cell culture-derived inactivated rabies virus vaccine)], which are intended for clinical use by intramuscular route in Rhesus monkeys. METHODS: As per the regulatory requirements, the study was designed for acute (single dose - 14 days), sub-chronic (repeat dose - 28 days) and chronic (intended clinical dose - 120 days) toxicity tests using three dose levels, viz. therapeutic, average (2x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in monkeys. The selection of the model i.e. monkey was based on affinity and rapid higher antibody response during the efficacy studies. An attempt was made to evaluate all parameters which included physical, physiological, clinical, haematological and histopathological profiles of all target organs, as well as Tiers I, II, III immunotoxicity parameters. RESULTS: In acute toxicity there was no mortality in spite of exposing the monkeys to 10XDRV. In sub chronic and chronic toxicity studies there were no abnormalities in physical, physiological, neurological, clinical parameters, after administration of test compound in intended and 10 times of clinical dosage schedule of DRV and CRV under the experimental conditions. Clinical chemistry, haematology, organ weights and histopathology studies were essentially unremarkable except the presence of residual DNA in femtogram level at site of injection in animal which received 10X DRV in chronic toxicity study. No Observational Adverse Effects Level (NOAEL) of DRV is 1000 ug/dose (10 times of therapeutic dose) if administered on 0, 4, 7, 14, 28(th) day. INTERPRETATION & CONCLUSIONS: The information generated by this study not only draws attention to the need for national and international regulatory agencies in formulating guidelines for pre-clinical safety evaluation of biotech products but also facilitates the development of biopharmaceuticals as safe potential therapeutic agents.",2013 Jun,"['Kumar, B. Dinesh', 'Kumar, P. Uday', 'Krishna, T. Prasanna', 'Kalyanasundaram, S.', 'Suresh, P.', 'Jagadeesan, V.', 'Hariharan, S.', 'Naidu, A. Nadamuni', 'Krishnaswamy, Kamala', 'Rangarajan, P.N.', 'Srinivasan, V.A.', 'Reddy, G.S.', 'Sesikeran, B.']",Indian J Med Res,,,
,PMC,The Zinc-Finger Domain Was Essential for Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein-1α to Inhibit the Production of Interferon-β,http://dx.doi.org/10.1089/jir.2012.0100,PMC3665301,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) has caused one of the most economically devastating and pandemic diseases of swine. Previous studies have documented that PRRSV nonstructural protein-1α (nsp1α) was an interferon antagonist, but the mechanism by which nsp1α inhibited the interferon (IFN)-β production was unclear. Here, by site-directed mutagenesis of the predicted zinc-coordinating residues of the zinc-finger (ZF) domain of nsp1α or by deletion of the ZF domain of nsp1α, we explored whether the ZF domain was required for nsp1α to disrupt the IFN-β production. The results showed that both mutagenesis of the predicted zinc-coordinating residues of the ZF domain and deletion of the ZF domain made nsp1α lose its interferon antagonism activity. In conclusion, our present work indicated that the ZF domain of nsp1α was necessary for nsp1α to inhibit the IFN-β induction.",,"['Shi, Xibao', 'Zhang, Xiaozhuan', 'Wang, Fangyu', 'Wang, Li', 'Qiao, Songlin', 'Guo, Junqing', 'Luo, Chunhui', 'Wan, Bo', 'Deng, Ruiguang', 'Zhang, Gaiping']",,,,
,PMC,Prevention of influenza at Hajj: applications for mass gatherings,http://dx.doi.org/10.1258/jrsm.2012.120170,PMC3705423,,,"Outbreaks of infectious diseases that spread via respiratory route, e.g. influenza, are common amongst Hajj congregation in Mecca, Saudi Arabia. The Saudi Arabian authority successfully organized the Hajj 2009 amidst fear of pandemic influenza. While severe influenza A(H1N1)pdm09 was rare, the true burden of pandemic influenza at Hajj that year remains speculative. In this article we review the latest evidence on influenza control and discuss our experience of influenza and its prevention at Hajj and possible application to other mass gatherings. Depending on study design the attack rate of seasonal influenza at Hajj has ranged from 6% in polymerase chain reaction or culture confirmed studies to 38% in serological surveillance. No significant effect of influenza vaccine or the use of personal protective measures against influenza has been established from observational studies, although the uptake of the vaccine and adherence to face masks and hand hygiene has been low. In all, there is a relatively poor evidence base for control of influenza. Until better evidence is obtained, vaccination coupled with rapid antiviral treatment of symptomatic individuals remains the mainstay of prevention at Hajj and other mass gatherings. Hajj pilgrimage provides a unique opportunity to test the effectiveness of various preventive measures that require a large sample size, such as testing the efficacy of plain surgical masks against laboratory-confirmed influenza. After successful completion of a pilot trial conducted among Australian pilgrims at the 2011 Hajj, a large multinational cluster randomized controlled trial is being planned. This will require effective international collaboration.",,"['Haworth, Elizabeth', 'Barasheed, Osamah', 'Memish, Ziad A', 'Rashid, Harunor', 'Booy, Robert']",,,,
,PMC,Complete Protection against Severe Acute Respiratory Syndrome Coronavirus-Mediated Lethal Respiratory Disease in Aged Mice by Immunization with a Mouse-Adapted Virus Lacking E Protein,http://dx.doi.org/10.1128/JVI.00087-13,PMC3676143,,,"Zoonotic coronaviruses, including the one that caused severe acute respiratory syndrome (SARS), cause significant morbidity and mortality in humans. No specific therapy for any human coronavirus is available, making vaccine development critical for protection against these viruses. We previously showed that recombinant SARS coronavirus (SARS-CoV) (Urbani strain based) lacking envelope (E) protein expression (rU-ΔE) provided good but not perfect protection in young mice against challenge with virulent mouse-adapted SARS-CoV (MA15). To improve vaccine efficacy, we developed a second set of E-deleted vaccine candidates on an MA15 background (rMA15-ΔE). rMA15-ΔE is safe, causing no disease in 6-week-, 12-month-, or 18-month-old BALB/c mice. Immunization with this virus completely protected mice of three ages from lethal disease and effected more-rapid virus clearance. Compared to rU-ΔE, rMA15-ΔE immunization resulted in significantly greater neutralizing antibody and SARS-CoV-specific CD4 and CD8 T cell responses. After challenge, inflammatory cell infiltration, edema, and lung destruction were decreased in the lungs of rMA15-ΔE-immunized mice compared to those in rU-ΔE-immunized 12-month-old mice. Collectively, these results show that immunization with a species-adapted attenuated coronavirus lacking E protein expression is safe and provides optimal immunogenicity and long-term protection against challenge with lethal virus. This approach will be generally useful for development of vaccines protective against human coronaviruses as well as against coronaviruses that cause disease in domestic and companion animals.",,"['Fett, Craig', 'DeDiego, Marta L.', 'Regla-Nava, Jose A.', 'Enjuanes, Luis', 'Perlman, Stanley']",,,,
,PMC,A Case for the Ancient Origin of Coronaviruses,http://dx.doi.org/10.1128/JVI.03273-12,PMC3676139,,,"Coronaviruses are found in a diverse array of bat and bird species, which are believed to act as natural hosts. Molecular clock dating analyses of coronaviruses suggest that the most recent common ancestor of these viruses existed around 10,000 years ago. This relatively young age is in sharp contrast to the ancient evolutionary history of their putative natural hosts, which began diversifying tens of millions of years ago. Here, we attempted to resolve this discrepancy by applying more realistic evolutionary models that have previously revealed the ancient evolutionary history of other RNA viruses. By explicitly modeling variation in the strength of natural selection over time and thereby improving the modeling of substitution saturation, we found that the time to the most recent ancestor common for all coronaviruses is likely far greater (millions of years) than the previously inferred range.",,"['Wertheim, Joel O.', 'Chu, Daniel K. W.', 'Peiris, Joseph S. M.', 'Kosakovsky Pond, Sergei L.', 'Poon, Leo L. M.']",,,,
,PMC,Tropism of and Innate Immune Responses to the Novel Human Betacoronavirus Lineage C Virus in Human Ex Vivo Respiratory Organ Cultures,http://dx.doi.org/10.1128/JVI.00009-13,PMC3676115,,,"Since April 2012, there have been 17 laboratory-confirmed human cases of respiratory disease associated with newly recognized human betacoronavirus lineage C virus EMC (HCoV-EMC), and 7 of them were fatal. The transmissibility and pathogenesis of HCoV-EMC remain poorly understood, and elucidating its cellular tropism in human respiratory tissues will provide mechanistic insights into the key cellular targets for virus propagation and spread. We utilized ex vivo cultures of human bronchial and lung tissue specimens to investigate the tissue tropism and virus replication kinetics following experimental infection with HCoV-EMC compared with those following infection with human coronavirus 229E (HCoV-229E) and severe acute respiratory syndrome coronavirus (SARS-CoV). The innate immune responses elicited by HCoV-EMC were also investigated. HCoV-EMC productively replicated in human bronchial and lung ex vivo organ cultures. While SARS-CoV productively replicated in lung tissue, replication in human bronchial tissue was limited. Immunohistochemistry revealed that HCoV-EMC infected nonciliated bronchial epithelium, bronchiolar epithelial cells, alveolar epithelial cells, and endothelial cells. Transmission electron microscopy showed virions within the cytoplasm of bronchial epithelial cells and budding virions from alveolar epithelial cells (type II). In contrast, there was minimal HCoV-229E infection in these tissues. HCoV-EMC failed to elicit strong type I or III interferon (IFN) or proinflammatory innate immune responses in ex vivo respiratory tissue cultures. Treatment of human lung tissue ex vivo organ cultures with type I IFNs (alpha and beta IFNs) at 1 h postinfection reduced the replication of HCoV-EMC, suggesting a potential therapeutic use of IFNs for treatment of human infection.",,"['Chan, Renee W. Y.', 'Chan, Michael C. W.', 'Agnihothram, Sudhakar', 'Chan, Louisa L. Y.', 'Kuok, Denise I. T.', 'Fong, Joanne H. M.', 'Guan, Y.', 'Poon, Leo L. M.', 'Baric, Ralph S.', 'Nicholls, John M.', 'Peiris, J. S. Malik']",,,,
,PMC,TMPRSS2 Activates the Human Coronavirus 229E for Cathepsin-Independent Host Cell Entry and Is Expressed in Viral Target Cells in the Respiratory Epithelium,http://dx.doi.org/10.1128/JVI.03372-12,PMC3648130,,,"Infection with human coronavirus 229E (HCoV-229E) is associated with the common cold and may result in pneumonia in immunocompromised patients. The viral spike (S) protein is incorporated into the viral envelope and mediates infectious entry of HCoV-229E into host cells, a process that depends on the activation of the S-protein by host cell proteases. However, the proteases responsible for HCoV-229E activation are incompletely defined. Here we show that the type II transmembrane serine proteases TMPRSS2 and HAT cleave the HCoV-229E S-protein (229E-S) and augment 229E-S-driven cell-cell fusion, suggesting that TMPRSS2 and HAT can activate 229E-S. Indeed, engineered expression of TMPRSS2 and HAT rendered 229E-S-driven virus-cell fusion insensitive to an inhibitor of cathepsin L, a protease previously shown to facilitate HCoV-229E infection. Inhibition of endogenous cathepsin L or TMPRSS2 demonstrated that both proteases can activate 229E-S for entry into cells that are naturally susceptible to infection. In addition, evidence was obtained that activation by TMPRSS2 rescues 229E-S-dependent cell entry from inhibition by IFITM proteins. Finally, immunohistochemistry revealed that TMPRSS2 is coexpressed with CD13, the HCoV-229E receptor, in human airway epithelial (HAE) cells, and that CD13(+) TMPRSS2(+) cells are preferentially targeted by HCoV-229E, suggesting that TMPRSS2 can activate HCoV-229E in infected humans. In sum, our results indicate that HCoV-229E can employ redundant proteolytic pathways to ensure its activation in host cells. In addition, our observations and previous work suggest that diverse human respiratory viruses are activated by TMPRSS2, which may constitute a target for antiviral intervention.",,"['Bertram, Stephanie', 'Dijkman, Ronald', 'Habjan, Matthias', 'Heurich, Adeline', 'Gierer, Stefanie', 'Glowacka, Ilona', 'Welsch, Kathrin', 'Winkler, Michael', 'Schneider, Heike', 'Hofmann-Winkler, Heike', 'Thiel, Volker', 'Pöhlmann, Stefan']",,,,
,PMC,Isolation and Characterization of Current Human Coronavirus Strains in Primary Human Epithelial Cell Cultures Reveal Differences in Target Cell Tropism,http://dx.doi.org/10.1128/JVI.03368-12,PMC3648119,,,"The human airway epithelium (HAE) represents the entry port of many human respiratory viruses, including human coronaviruses (HCoVs). Nowadays, four HCoVs, HCoV-229E, HCoV-OC43, HCoV-HKU1, and HCoV-NL63, are known to be circulating worldwide, causing upper and lower respiratory tract infections in nonhospitalized and hospitalized children. Studies of the fundamental aspects of these HCoV infections at the primary entry port, such as cell tropism, are seriously hampered by the lack of a universal culture system or suitable animal models. To expand the knowledge on fundamental virus-host interactions for all four HCoVs at the site of primary infection, we used pseudostratified HAE cell cultures to isolate and characterize representative clinical HCoV strains directly from nasopharyngeal material. Ten contemporary isolates were obtained, representing HCoV-229E (n = 1), HCoV-NL63 (n = 1), HCoV-HKU1 (n = 4), and HCoV-OC43 (n = 4). For each strain, we analyzed the replication kinetics and progeny virus release on HAE cell cultures derived from different donors. Surprisingly, by visualizing HCoV infection by confocal microscopy, we observed that HCoV-229E employs a target cell tropism for nonciliated cells, whereas HCoV-OC43, HCoV-HKU1, and HCoV-NL63 all infect ciliated cells. Collectively, the data demonstrate that HAE cell cultures, which morphologically and functionally resemble human airways in vivo, represent a robust universal culture system for isolating and comparing all contemporary HCoV strains.",,"['Dijkman, Ronald', 'Jebbink, Maarten F.', 'Koekkoek, Sylvie M.', 'Deijs, Martin', 'Jónsdóttir, Hulda R.', 'Molenkamp, Richard', 'Ieven, Margareta', 'Goossens, Herman', 'Thiel, Volker', 'van der Hoek, Lia']",,,,
,PMC,Deciphering the Mechanism of Defective Interfering RNA (DI RNA) Biogenesis Reveals That a Viral Protein and the DI RNA Act Antagonistically in Virus Infection,http://dx.doi.org/10.1128/JVI.03322-12,PMC3648117,,,"Potato mop-top virus (PMTV) produces a defective RNA (D RNA) encompassing the 5′-terminal 479 nucleotides (nt) and 3′-terminal 372 nt of RNA-TGB (where TGB is triple gene block). The mechanism that controls D RNA biogenesis and the role of D RNA in virus accumulation was investigated by introducing deletions, insertions, and point mutations into the sequences of the open reading frames (ORFs) of TGB1 and the 8-kilodalton (8K) protein that were identified as required for efficient production of the D RNA. Transient expression of RNA-TGB in the absence of RNA-Rep (which encodes the replicase) did not result in accumulation of D RNA, indicating that its production is dependent on PMTV replication. The D RNA could be eliminated by disrupting a predicted minus-strand stem-loop structure comprising complementary sequences of the 5′ TGB1 ORF and the 3′ 8K ORF, suggesting intramolecular template switching during positive-strand synthesis as a mechanism for the D RNA biogenesis. Virus accumulation was reduced when the 8K ORF was disrupted but D RNA was produced. Conversely, the virus accumulated at higher titers when the 8K ORF was intact and D RNA production was blocked. These data demonstrate that the D RNA interferes with virus infection and therefore should be referred to as a defective interfering RNA (DI RNA). The 8K protein was shown to be a weak silencing suppressor. This study provides an example of the interplay between a pathogen and its molecular parasite where virus accumulation was differentially regulated by the 8K protein and DI RNA, indicating that they play antagonistic roles and suggesting a mechanism by which the virus can attenuate replication, decreasing viral load and thereby enhancing its efficiency as a parasite.",,"['Lukhovitskaya, Nina I.', 'Thaduri, Srinivas', 'Garushyants, Sonya K.', 'Torrance, Lesley', 'Savenkov, Eugene I.']",,,,
,PMC,"MDA5 Localizes to Stress Granules, but This Localization Is Not Required for the Induction of Type I Interferon",http://dx.doi.org/10.1128/JVI.03213-12,PMC3648107,,,"Virus infection can initiate a type I interferon (IFN-α/β) response via activation of the cytosolic RNA sensors retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). Furthermore, it can activate kinases that phosphorylate eukaryotic translation initiation factor 2α (eIF2α), which leads to inhibition of (viral) protein translation and formation of stress granules (SG). Most viruses have evolved mechanisms to suppress these cellular responses. Here, we show that a mutant mengovirus expressing an inactive leader (L) protein, which we have previously shown to be unable to suppress IFN-α/β, triggered SG formation in a protein kinase R (PKR)-dependent manner. Furthermore, we show that infection of cells that are defective in SG formation yielded higher viral RNA levels, suggesting that SG formation acts as an antiviral defense mechanism. Since the induction of both IFN-α/β and SG is suppressed by mengovirus L, we set out to investigate a potential link between these pathways. We observed that MDA5, the intracellular RNA sensor that recognizes picornaviruses, localized to SG. However, activation of the MDA5 signaling pathway did not trigger and was not required for SG formation. Moreover, cells that were unable to form SG—by protein kinase R (PKR) depletion, using cells expressing a nonphosphorylatable eIF2α protein, or by drug treatment that inhibits SG formation—displayed a normal IFN-α/β response. Thus, although MDA5 localizes to SG, this localization seems to be dispensable for induction of the IFN-α/β pathway.",,"['Langereis, Martijn A.', 'Feng, Qian', 'van Kuppeveld, Frank J.']",,,,
,PMC,Griffithsin Protects Mice from Genital Herpes by Preventing Cell-to-Cell Spread,http://dx.doi.org/10.1128/JVI.00012-13,PMC3648100,,,"Griffithsin, which binds N-linked glycans on gp120 to prevent HIV entry, has the most potent HIV-1 inhibitory activity described for any antiviral lectin and is being developed for topical preexposure prophylaxis. The current studies were designed to further assess its potential by exploring its activity against herpes simplex virus 2 (HSV-2), a cofactor for HIV acquisition, in vitro and in a murine model. Safety was evaluated by examining its impact on epithelial barrier integrity in polarized cultures and testing whether repeated intravaginal dosing potentiates the susceptibility of mice to genital herpes. Griffithsin displayed modest inhibitory activity against HSV-2 if present during viral entry but completely blocked plaque formation if present postentry, reduced plaque size, and prevented cell-to-cell spread. These in vitro findings translated to significant protection against genital herpes in mice treated with 0.1% griffithsin gel. Griffithsin, but not placebo gel, prevented viral spread (visualized with a luciferase-expressing virus), significantly reduced disease scores, and resulted in greater survival (P < 0.05, log rank test). Protection persisted when HSV-2 was introduced in seminal plasma. Although griffithsin triggered a small decline in transepithelial electrical resistance in polarized cultures, this did not translate to any significant increase in the ability of HIV to migrate from the apical to the basolateral chamber nor to an increase in susceptibility to HSV-2 in mice treated with griffithsin gel for 7 days. These findings demonstrate that griffithsin inhibits HSV-2 by a unique mechanism of blocking cell-to-cell spread and support its further development for HIV and HSV-2 prevention.",,"['Nixon, Briana', 'Stefanidou, Martha', 'Mesquita, Pedro M. M.', 'Fakioglu, Esra', 'Segarra, Theodore', 'Rohan, Lisa', 'Halford, William', 'Palmer, Kenneth E.', 'Herold, Betsy C.']",,,,
,PMC,Identification and Characterization of Genetically Divergent Members of the Newly Established Family Mesoniviridae,http://dx.doi.org/10.1128/JVI.00416-13,PMC3648093,,,"The recently established family Mesoniviridae (order Nidovirales) contains a single species represented by two closely related viruses, Cavally virus (CavV) and Nam Dinh virus (NDiV), which were isolated from mosquitoes collected in Côte d'Ivoire and Vietnam, respectively. They represent the first nidoviruses to be discovered in insects. Here, we report the molecular characterization of four novel mesoniviruses, Hana virus, Méno virus, Nsé virus, and Moumo virus, all of which were identified in a geographical region in Côte d'Ivoire with high CavV prevalence. The viruses were found with prevalences between 0.5 and 2.8%, and genome sequence analyses and phylogenetic studies suggest that they represent at least three novel species. Electron microscopy revealed prominent club-shaped surface projections protruding from spherical, enveloped virions of about 120 nm. Northern blot data show that the four mesoniviruses analyzed in this study produce two major 3′-coterminal subgenomic mRNAs containing two types of 5′ leader sequences resulting from the use of different pairs of leader and body transcription-regulating sequences that are conserved among mesoniviruses. Protein sequencing, mass spectroscopy, and Western blot data show that mesonivirus particles contain eight major structural protein species, including the putative nucleocapsid protein (25 kDa), differentially glycosylated forms of the putative membrane protein (20, 19, 18, and 17 kDa), and the putative spike (S) protein (77 kDa), which is proteolytically cleaved at a conserved site to produce S protein subunits of 23 and 57 kDa. The data provide fundamental new insight into common and distinguishing biological properties of members of this newly identified virus family.",,"['Zirkel, Florian', 'Roth, Hanna', 'Kurth, Andreas', 'Drosten, Christian', 'Ziebuhr, John', 'Junglen, Sandra']",,,,
,PMC,Structure-Function Analysis of Severe Acute Respiratory Syndrome Coronavirus RNA Cap Guanine-N7-Methyltransferase,http://dx.doi.org/10.1128/JVI.00061-13,PMC3648086,,,"Coronaviruses possess a cap structure at the 5′ ends of viral genomic RNA and subgenomic RNAs, which is generated through consecutive methylations by virally encoded guanine-N7-methyltransferase (N7-MTase) and 2′-O-methyltransferase (2′-O-MTase). The coronaviral N7-MTase is unique for its physical linkage with an exoribonuclease (ExoN) harbored in nonstructural protein 14 (nsp14) of coronaviruses. In this study, the structure-function relationships of the N7-MTase were analyzed by deletion and site-directed mutagenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) nsp14. The results showed that the ExoN domain is closely involved in the activity of the N7-MTase, suggesting that coronavirus N7-MTase is different from all other viral N7-MTases, which are separable from other structural domains located in the same polypeptide. Two of the 12 critical residues identified to be essential for the N7-MTase were located at the N terminus of the core ExoN domain, reinforcing a role of the ExoN domain in the N7-MTase activity of nsp14. The other 10 critical residues were distributed throughout the N7-MTase domain but localized mainly in the S-adenosyl-l-methionine (SAM)-binding pocket and key structural elements of the MTase fold of nsp14. The sequence motif DxGxPxA (amino acids [aa] 331 to 338) was identified as the key part of the SAM-binding site. These results provide insights into the structure and functional mechanisms of coronaviral nsp14 N7-MTase.",,"['Chen, Yu', 'Tao, Jiali', 'Sun, Ying', 'Wu, Andong', 'Su, Ceyang', 'Gao, Guozhen', 'Cai, Hui', 'Qiu, Su', 'Wu, Yingliang', 'Ahola, Tero', 'Guo, Deyin']",,,,
,PMC,"Regulation of Hepatitis B Virus Infection by Rab5, Rab7, and the Endolysosomal Compartment",http://dx.doi.org/10.1128/JVI.00393-13,PMC3648082,,,"Despite important progress toward deciphering human hepatitis B virus (HBV) entry into host cells, many aspects of the early steps of the life cycle remained completely obscure. Following endocytosis, HBV must travel through the complex network of the endocytic pathway to reach the cell nucleus and initiate replication. In addition to guiding the viral particles to the replication site, the endosomal vesicles may play a crucial role in infection, providing the appropriate environment for virus uncoating and nucleocapsid release. In this work, we investigated the trafficking of HBV particles internalized in permissive cells. Expression of key Rab proteins, involved in specific pathways leading to different intracellular locations, was modulated in HepaRG cells, using a stable and inducible short hairpin RNA (shRNA) expression system. The trafficking properties of the newly developed cells were demonstrated by confocal microscopy and flow cytometry using specific markers. The results showed that HBV infection strongly depends on Rab5 and Rab7 expression, indicating that HBV transport from early to mature endosomes is required for a step in the viral life cycle. This may involve reduction of disulfide bond-linked envelope proteins, as alteration of the redox potential of the endocytic pathway resulted in inhibition of infection. Subcellular fractionation of HBV-infected cells showed that viral particles are further transported to lysosomes. Intriguingly, infection was not dependent on the lysosomal activity, suggesting that trafficking to this compartment is a “dead-end” route. Together, these data add to our understanding of the HBV-host cell interactions controlling the early stages of infection.",,"['Macovei, Alina', 'Petrareanu, Catalina', 'Lazar, Catalin', 'Florian, Paula', 'Branza-Nichita, Norica']",,,,
,PMC,The Unexpected Roles of Eukaryotic Translation Elongation Factors in RNA Virus Replication and Pathogenesis,http://dx.doi.org/10.1128/MMBR.00059-12,PMC3668672,,,"SUMMARY: The prokaryotic translation elongation factors were identified as essential cofactors for RNA-dependent RNA polymerase activity of the bacteriophage Qβ more than 40 years ago. A growing body of evidence now shows that eukaryotic translation elongation factors (eEFs), predominantly eEF1A, acting in partially characterized complexes sometimes involving additional eEFs, facilitate virus replication. The functions of eEF1A as a protein chaperone and an RNA- and actin-binding protein enable its “moonlighting” roles as a virus replication cofactor. A diverse group of viruses, from human immunodeficiency type 1 and West Nile virus to tomato bushy stunt virus, have adapted to use eEFs as cofactors for viral transcription, translation, assembly, and pathogenesis. Here we review the mechanisms used by viral pathogens to usurp these abundant cellular proteins for their replication.",,"['Li, Dongsheng', 'Wei, Ting', 'Abbott, Catherine M.', 'Harrich, David']",,,,
,PMC,Monoclonal Antibodies Directed Against Chicken β2-Microglobulin Developed With a Synthesized Peptide,http://dx.doi.org/10.1089/mab.2013.0001,PMC3733132,,,"We developed a panel of monoclonal antibodies (MAb) against chicken β2-microglobulin (chβ2M) by fusions between SP2/0 myeloma cells and spleen cells from mice immunized with a synthesized peptide corresponding to positions 91-119 of the COOH domain of chβ2M. Two of them, 6E7 and 3D1, identified as IgG1/κ, could react with chβ2M protein from avian macrophage HD11 cells and human 293T cells transfected with pcDNA3.1-chβ2M in immunofluorescence assays. Only a 12 kDa protein band of chβ2M could be detected in the HD11 and 293T/chβ2M cell lysates by Western blot analysis. Chicken β2M in serum and plasma could be found in Western blot by MAb 3D1. Moreover, MAb 3D1 also recognized the chβ2M antigen on the cell membranes in flow cytometry. Immunohistochemical staining with these MAbs revealed that chβ2M was present in chicken thymus, spleen, and bursa. These MAbs will be good tools for analyzing the mechanism of the chicken immune system.",,"['Yu, Chuan', 'Liu, Qiu', 'Gao, Wei', 'Qian, Kun', 'Mei, Mei', 'Shao, Hong-Xia', 'Wu, Gen-Hua', 'Jin, Wen-Jie', 'Qin, Ai-Jian']",,,,
,PMC,Lessons learned and unlearned in periodontal microbiology,http://dx.doi.org/10.1111/prd.12010,PMC3912758,,,"Periodontal diseases are initiated by bacterial species living in polymicrobial biofilms at or below the gingival margin and progress largely as a result of the inflammation initiated by specific subgingival species. In the past few decades, efforts to understand the microbiota of periodontal diseases have led to an exponential increase in information about biofilms associated with periodontal health and disease. In fact, the oral microbiota is one of the best characterized microbiomes that colonize the human body. Despite this increased knowledge, one has to ask if our fundamental concepts of the etiology and pathogenesis of periodontal diseases have really changed. In this chapter we will review how our comprehension of the structure and function of the subgingival microbiota evolved over the years in search of lessons learned and unlearned in periodontal microbiology. More specifically, this review focuses on: 1) how the data obtained through molecular techniques has impacted our knowledge of the etiology of periodontal infections; 2) the potential role of viruses in the etiopathogenesis of periodontal diseases; 3) how concepts of microbial ecology have expanded our understanding of host microbial interactions that might lead to periodontal diseases; 4) the role of inflammation in the pathogenesis of periodontal diseases; and 5) the impact of these evolving concepts on treatment and preventive approaches to periodontal infections. We will conclude by reviewing how novel systems biology approaches promise to unravel new details of the pathogenesis of periodontal diseases and, hopefully, lead to a better understanding of periodontal disease mechanisms.",,"['Teles, Ricardo', 'Teles, Flavia', 'Frias-Lopez, Jorge', 'Paster, Bruce', 'Haffajee, Anne']",,,,
,PMC,The Novel H7N9 Influenza A Virus: Its Present Impact and Indeterminate Future,http://dx.doi.org/10.1089/vbz.2013.999.ceezad,PMC3709519,,,,,"['Kahn, Robert E.', 'Richt, Juergen A.']",,,,
,PMC,"Genetic and Biological Characterization of Tick-Borne Encephalitis Virus Isolated from Wild Rodents in Southern Hokkaido, Japan in 2008",http://dx.doi.org/10.1089/vbz.2012.1231,PMC3669602,,,"Tick-borne encephalitis virus (TBEV) is a zoonotic agent causing severe encephalitis in humans. A recent epizootiological survey indicated that endemic foci of TBEV have been maintained in the southern part of Hokkaido until recently. In this study, we sought to isolate TBEV from wild rodents in the area. One virus, designated Oshima 08-As, was isolated from an Apodemus speciosus captured in Hokuto in 2008. Oshima 08-As was classified as the Far Eastern subtype of TBEV and formed a cluster with the other strains isolated in Hokkaido from 1995 to 1996. Thirty-six nucleotide differences resulted in 12 amino acid changes between Oshima 08-As and Oshima 5–10 isolated in 1995. Oshima 08-As caused high mortality and morbidity in a mouse model compared with Oshima 5–10. Although similar transient viral multiplication in the spleen was observed in the mice infected with Oshima 08-As and Oshima 5–10, greater viral multiplication with an inflammatory response was noted in the brains of mice infected with Oshima 08-As than those infected with Oshima 5–10. These data indicate that a few naturally occurring mutations affect the pathogenicity of the Oshima strains endemic in the southern part of Hokkaido.",,"['Kentaro, Yoshii', 'Yamazaki, Shoko', 'Mottate, Keita', 'Nagata, Noriyo', 'Seto, Takahiro', 'Sanada, Takashiro', 'Sakai, Mizuki', 'Kariwa, Hiroaki', 'Takashima, Ikuo']",,,,
,PMC,Serological Evidence of Toxoplasma gondii Infection in Five Species of Bats in China,http://dx.doi.org/10.1089/vbz.2012.1091,PMC3669597,,,"Toxoplasma gondii is an obligate intracellular protozoan parasite that can infect almost all warm-blooded animals and humans with a worldwide distribution. Bats are reservoirs for an increasing number of emerging zoonotic viruses, such as henipaviruses and severe acute respiratory syndrome coronavirus (SARS-CoV). However, little is known of T. gondii infection in bats. The objective of the present study was to determine the seroprevalence of T. gondii infection in bats in China. A total of 217 serum samples from 5 species of bats were collected between April, 2010, and August, 2011, from 4 provinces in China. Antibodies to T. gondii were determined using the modified agglutination test (MAT, 1:25 or higher). Antibodies to T. gondii were found in 26.5% (18/68) Megaderma lyra, 13.6% (12/88) Rousettus leschenaulti, 13.6% (3/22) Cynopterus sphinx, 20% (4/20) Vespertilio superaus, and 15.8% (3/19) Pipistrellus javanicus. Antibody titers ranged from 1:25 to 1:400, with titers of 1:200 detected in 4 of the 5 bat species. The present study suggests the likely occurrence of T. gondii infection in bats in China, and these bats are new putative hosts for T. gondii, which may pose a threat to human health.",,"['Yuan, Zi-Guo', 'Luo, Sheng-Jun', 'Dubey, Jitender P.', 'Zhou, Dong-Hui', 'Zhu, Yan-Ping', 'He, Yong', 'He, Xian-Hui', 'Zhang, Xiu-Xiang', 'Zhu, Xing-Quan']",,,,
,PMC,Rapid characterization of microorganisms by mass spectrometry - What can be learned and how?,http://dx.doi.org/10.1007/s13361-013-0660-7,PMC3715556,,,"Strategies for the rapid and reliable analysis of microorganisms have been sought to meet national needs in defense, homeland security, space exploration, food and water safety, and clinical diagnosis. Mass spectrometry has long been a candidate technique because it is extremely rapid and can provide highly specific information. It has excellent sensitivity. Molecular and fragment ion masses provide detailed fingerprints, which can also be interpreted. Mass spectrometry is also a broad band method—everything has a mass—and it is automatable. Mass spectrometry is a physiochemical method that is orthogonal and complementary to biochemical and morphological methods used to characterize microorganisms.",,"Fenselau, Catherine",,,,
,PMC,Inducible Interleukin 32 (IL-32) Exerts Extensive Antiviral Function via Selective Stimulation of Interferon λ1 (IFN-λ1),http://dx.doi.org/10.1074/jbc.M112.440115,PMC3774363,,,"Interleukin (IL)-32 has been recognized as a proinflammatory cytokine that participates in responses to viral infection. However, little is known about how IL-32 is induced in response to viral infection and the mechanisms of IL-32-mediated antiviral activities. We discovered that IL-32 is elevated by hepatitis B virus (HBV) infection both in vitro and in vivo and that HBV induced IL-32 expression at the level of both transcription and post-transcription. Furthermore, microRNA-29b was found to be a key factor in HBV-regulated IL-32 expression by directly targeting the mRNA 3′-untranslated region of IL-32. Antiviral analysis showed that IL-32 was not sufficient to alter HBV replication in HepG2.2.15 cells. To mimic the viremic phase of viral infection, freshly isolated peripheral blood mononuclear cells were treated with IL-32γ, the secretory isoform, and the supernatants were used for antiviral assays. Surprisingly, these supernatants exhibited extensive antiviral activity against multiplex viruses besides HBV. Thus, we speculated that the IL-32γ-treated peripheral blood mononuclear cells produced and secreted an unknown antiviral factor. Using antibody neutralization assays, we identified the factor as interferon (IFN)-λ1 and not IFN-α. Further studies indicated that IL-32γ effectively inhibited HBV replication in a hydrodynamic injection mouse model. Clinical data showed that elevated levels of IFN-λ1 both in serum and liver tissue of HBV patients were positively correlated to the increased levels of IL-32. Our results demonstrate that elevated IL-32 levels during viral infection mediate antiviral effects by stimulating the expression of IFN-λ1.",,"['Li, Yongkui', 'Xie, Jiajia', 'Xu, Xiupeng', 'Liu, Li', 'Wan, Yushun', 'Liu, Yingle', 'Zhu, Chengliang', 'Zhu, Ying']",,,,
,PMC,"Health Care Worker Perspectives on Workplace Safety, Infection Control and Drug-Resistant Tuberculosis in a High Burden HIV setting",http://dx.doi.org/10.1057/jphp.2013.20,PMC4003866,,,"Drug-resistant tuberculosis (TB) is an occupational hazard for health care workers (HCWs) in South Africa. We undertook this qualitative study to contextualize epidemiological findings suggesting that HCWs elevated risk of drug-resistant TB is related to workplace exposure. 55 HCWs and 7 hospital managers participated in focus groups and interviews about infection control (IC). Participants discussed caring for patients with drug-resistant TB, IC measures, occupational health programs, and stigma and support in the workplace. Key themes included: 1) lack of resources that hinders IC, 2) distrust of IC efforts among HCWs, and 3) disproportionate focus on individual level personal protections, particularly N95 masks. IC programs should be evaluated, and the impact of new policies to rapidly diagnose drug-resistant TB and decentralize treatment should be assessed as part of the effort to control drug-resistant TB and create a safe workplace.",,"['Zelnick, JR', 'Gibbs, A', 'Loveday, M', 'Padayatchi, N', 'O’Donnell, MR']",,,,
,PMC,Hybrid DNA virus in Chinese patients with seronegative hepatitis discovered by deep sequencing,http://dx.doi.org/10.1073/pnas.1303744110,PMC3690853,,,"Seronegative hepatitis—non-A, non-B, non-C, non-D, non-E hepatitis—is poorly characterized but strongly associated with serious complications. We collected 92 sera specimens from patients with non-A–E hepatitis in Chongqing, China between 1999 and 2007. Ten sera pools were screened by Solexa deep sequencing. We discovered a 3,780-bp contig present in all 10 pools that yielded BLASTx E scores of 7e-05–0.008 against parvoviruses. The complete sequence of the in silico-assembled 3,780-bp contig was confirmed by gene amplification of overlapping regions over almost the entire genome, and the virus was provisionally designated NIH-CQV. Further analysis revealed that the contig was composed of two major ORFs. By protein BLAST, ORF1 and ORF2 were most homologous to the replication-associated protein of bat circovirus and the capsid protein of porcine parvovirus, respectively. Phylogenetic analysis indicated that NIH-CQV is located at the interface of Parvoviridae and Circoviridae. Prevalence of NIH-CQV in patients was determined by quantitative PCR. Sixty-three of 90 patient samples (70%) were positive, but all those from 45 healthy controls were negative. Average virus titer in the patient specimens was 1.05 e4 copies/µL. Specific antibodies against NIH-CQV were sought by immunoblotting. Eighty-four percent of patients were positive for IgG, and 31% were positive for IgM; in contrast, 78% of healthy controls were positive for IgG, but all were negative for IgM. Although more work is needed to determine the etiologic role of NIH-CQV in human disease, our data indicate that a parvovirus-like virus is highly prevalent in a cohort of patients with non-A–E hepatitis.",,"['Xu, Baoyan', 'Zhi, Ning', 'Hu, Gangqing', 'Wan, Zhihong', 'Zheng, Xiaobin', 'Liu, Xiaohong', 'Wong, Susan', 'Kajigaya, Sachiko', 'Zhao, Keji', 'Mao, Qing', 'Young, Neal S.']",,,,
,PMC,Antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens,http://dx.doi.org/10.1073/pnas.1303573110,PMC3683766,,,"Microbial capsular antigens are effective vaccines but are chemically and immunologically diverse, resulting in a major barrier to their use against multiple pathogens. A β-(1→6)–linked poly-N-acetyl-d-glucosamine (PNAG) surface capsule is synthesized by four proteins encoded in genetic loci designated intercellular adhesion in Staphylococcus aureus or polyglucosamine in selected Gram-negative bacterial pathogens. We report that many microbial pathogens lacking an identifiable intercellular adhesion or polyglucosamine locus produce PNAG, including Gram-positive, Gram-negative, and fungal pathogens, as well as protozoa, e.g., Trichomonas vaginalis, Plasmodium berghei, and sporozoites and blood-stage forms of Plasmodium falciparum. Natural antibody to PNAG is common in humans and animals and binds primarily to the highly acetylated glycoform of PNAG but is not protective against infection due to lack of deposition of complement opsonins. Polyclonal animal antibody raised to deacetylated glycoforms of PNAG and a fully human IgG1 monoclonal antibody that both bind to native and deacetylated glycoforms of PNAG mediated complement-dependent opsonic or bactericidal killing and protected mice against local and/or systemic infections by Streptococcus pyogenes, Streptococcus pneumoniae, Listeria monocytogenes, Neisseria meningitidis serogroup B, Candida albicans, and P. berghei ANKA, and against colonic pathology in a model of infectious colitis. PNAG is also a capsular polysaccharide for Neisseria gonorrhoeae and nontypable Hemophilus influenzae, and protects cells from environmental stress. Vaccination targeting PNAG could contribute to immunity against serious and diverse prokaryotic and eukaryotic pathogens, and the conserved production of PNAG suggests that it is a critical factor in microbial biology.",,"['Cywes-Bentley, Colette', 'Skurnik, David', 'Zaidi, Tanweer', 'Roux, Damien', 'DeOliveira, Rosane B.', 'Garrett, Wendy S.', 'Lu, Xi', 'O’Malley, Jennifer', 'Kinzel, Kathryn', 'Zaidi, Tauqeer', 'Rey, Astrid', 'Perrin, Christophe', 'Fichorova, Raina N.', 'Kayatani, Alexander K. K.', 'Maira-Litràn, Tomas', 'Gening, Marina L.', 'Tsvetkov, Yury E.', 'Nifantiev, Nikolay E.', 'Bakaletz, Lauren O.', 'Pelton, Stephen I.', 'Golenbock, Douglas T.', 'Pier, Gerald B.']",,,,
,PMC,First generation inhibitors of the adenovirus proteinase,http://dx.doi.org/10.1016/j.febslet.2013.05.033,PMC3810942,,,"As there are more than 50 Adenovirus serotypes, the likelihood of developing an effective vaccine is low. Here we describe inhibitors of the adenovirus proteinase (AVP) with the ultimate objective of developing anti-adenovirus agents. Inhibitors were identified via structure-based drug design using as druggable sites the active site and a conserved cofactor pocket in the crystal structures of AVP. A lead compound was identified that had an IC(50) of 18 μM. One of eight structural derivatives of the lead compound had an IC(50) of 140 nM against AVP and an IC(50) of 490 nM against the AVP with its cofactor bound.",,"['McGrath, William J.', 'Graziano, Vito', 'Zabrocka, Katarzyna', 'Mangel, Walter F.']",,,,
,PMC,Virome genomics: a tool for defining the human virome,http://dx.doi.org/10.1016/j.mib.2013.04.006,PMC3755052,,,"High throughput, deep sequencing assays are powerful tools for gaining insights into virus-host interactions. Sequencing assays can discover novel viruses and describe the genomes of novel and known viruses. Genomic information can predict viral proteins that can be characterized, describe important genes in the host that control infections, and evaluate gene expression of viruses and hosts during infection. Sequencing can also describe variation and evolution of viruses during replication and transmission. This review recounts some of the major advances in the studies of virus-host interactions from the last two years, and discusses the uses of sequencing technologies relating to these studies.",,"['Wylie, Kristine M.', 'Weinstock, George M.', 'Storch, Gregory A.']",,,,
,PMC,Low Levels of IGF-1 Contribute to Alveolar Macrophage Dysfunction in Cystic Fibrosis,http://dx.doi.org/10.4049/jimmunol.1300221,PMC3691334,,,"Alveolar macrophages are major contributors to lung innate immunity. Although alveolar macrophages from CFTR−/− mice have impaired function, no study has investigated primary alveolar macrophages in adults with cystic fibrosis (CF). CF patients have low levels of insulin-like growth factor 1 (IGF-1), and our prior studies demonstrate a relationship between IGF-1 and macrophage function. We hypothesize that reduced IGF-1 in CF leads to impaired alveolar macrophage function and chronic infections. Serum and bronchoalveolar lavage (BAL) samples were obtained from 8 CF subjects and 8 healthy subjects. Macrophages were isolated from BAL fluid. We measured the ability of alveolar macrophages to kill Pseudomonas aeruginosa. Subsequently, macrophages were incubated with IGF-1 prior to inoculation with bacteria to determine the effect of IGF-1 on bacterial killing. We found a significant decrease in bacterial killing by CF alveolar macrophages compared to controls. CF subjects had lower serum and BAL IGF-1 levels compared to healthy controls. Exposure to IGF-1 enhanced alveolar macrophage macrophages in both groups. Finally, exposing healthy alveolar macrophages to CF BAL fluid decreased bacterial killing, and this was reversed by the addition of IGF-1, while IGF-1 blockade worsened bacterial killing. Our studies demonstrate that alveolar macrophage function is impaired in patients with CF. Reductions in IGF-1 levels in CF contribute to the impaired alveolar macrophage function. Exposure to IGF-1 ex vivo, results in improved function of CF alveolar macrophages. Further studies are needed to determine whether alveolar macrophage function can be enhanced in vivo with IGF-1 treatment.",,"['Bessich, Jamie L.', 'Nymon, Amanda B.', 'Moulton, Lisa A', 'Dorman, Dana', 'Ashare, Alix']",,,,
,PMC,Avian influenza A(H7N9) and the closure of live bird markets,http://dx.doi.org/10.5365/WPSAR.2013.4.2.008,PMC3762972,,,,,"['Murhekar, Manoj', 'Arima, Yuzo', 'Horby, Peter', 'Vandemaele, Katelijn AH', 'Vong, Sirenda', 'Zijian, Feng', 'Lee, Chin-Kei', 'Li, Ailan', None, None]",,,,
,PMC,Nanoplasmonic Quantitative Detection of Intact Viruses from Unprocessed Whole Blood,http://dx.doi.org/10.1021/nn3036232,PMC3700402,,,"Infectious diseases such as HIV and Hepatitis B infection pose an omnipresent threat to global health. Reliable, fast, accurate and sensitive platforms that can be deployed at the point-of-care (POC) in multiple settings, such as airports and offices for detection of infectious pathogens are essential for the management of epidemics and possible biological attacks. To the best of our knowledge, no viral load technology adaptable to the POC settings exists today due to critical technical and biological challenges. Here, we present for the first time a broadly applicable technology for quantitative, nanoplasmonic-based intact virus detection at clinically relevant concentrations. The sensing platform is based on unique nanoplasmonic properties of nanoparticles utilizing immobilized antibodies to selectively capture rapidly evolving viral subtypes. We demonstrate the capture, detection and quantification of multiple HIV subtypes (A, B, C, D, E, G, and subtype panel) with high repeatability, sensitivity and specificity down to 98 ± 39 copies/mL (i.e., subtype D) using spiked whole blood samples and clinical discarded HIV-infected patient whole blood samples validated by the gold standard, i.e., RT-qPCR. This platform technology offers an assay time of 1 hour and 10 minutes (1 hour for capture, 10 minutes for detection and data analysis). The presented platform is also able to capture intact viruses at high efficiency using immuno-surface chemistry approaches directly from whole blood samples without any sample preprocessing steps such as spin-down or sorting. Evidence is presented showing the system to be accurate, repeatable and reliable. Additionally, the presented platform technology can be broadly adapted to detect other pathogens having reasonably well-described biomarkers by adapting the surface chemistry. Thus, this broadly applicable detection platform holds great promise to be implemented potentially at POC settings, hospital and primary care settings.",,"['Inci, Fatih', 'Tokel, Onur', 'Wang, ShuQi', 'Gurkan, Umut Atakan', 'Tasoglu, Savas', 'Kuritzkes, Daniel R.', 'Demirci, Utkan']",,,,
,PMC,In vitro reconstitution of lipid-dependent dual topology and postassembly topological switching of a membrane protein,http://dx.doi.org/10.1073/pnas.1304375110,PMC3677496,,,"Phospholipids could exert their effect on membrane protein topology either directly by interacting with topogenic signals of newly inserted proteins or indirectly by influencing the protein assembly machinery. In vivo lactose permease (LacY) of Escherichia coli displays a mixture of topological conformations ranging from complete inversion of the N-terminal helical bundle to mixed topology and then to completely native topology as phosphatidylethanolamine (PE) is increased from 0% to 70% of membrane phospholipids. These topological conformers are interconvertible by postassembly synthesis or dilution of PE in vivo. To investigate whether coexistence of multiple topological conformers is dependent solely on the membrane lipid composition, we determined the topological organization of LacY in an in vitro proteoliposome system in which lipid composition can be systematically controlled before (liposomes) and after (fliposomes) reconstitution using a lipid exchange technique. Purified LacY reconstituted into preformed liposomes of increasing PE content displayed inverted topology at low PE and then a mixture of inverted and proper topologies with the latter increasing with increasing PE until all LacY adopted its native topology. Interconversion between topological conformers of LacY was observed in a PE dose-dependent manner by either increasing or decreasing PE levels in proteoliposomes postreconstitution of LacY, clearly demonstrating that membrane protein topology can be changed simply by changing membrane lipid composition independent of other cellular factors. The results provide a thermodynamic-based lipid-dependent model for shifting the equilibrium between different conformational states of a membrane protein.",,"['Vitrac, Heidi', 'Bogdanov, Mikhail', 'Dowhan, William']",,,,
,PMC,Analysis of SARS-CoV E protein ion channel activity by tuning the protein and lipid charge,http://dx.doi.org/10.1016/j.bbamem.2013.05.008,PMC3715572,,,"A partial characterization of the ion channels formed by the SARS coronavirus (CoV) envelope (E) protein was previously reported [C. Verdiá-Báguena et al., 2012]. Here, we provide new significant insights on the involvement of lipids in the structure and function of the CoV E protein channel on the basis of three series of experiments. First, reversal potential measurements over a wide range of pH allows the dissection of the contributions to channel selectivity coming from ionizable residues of the protein transmembrane domain and also from the negatively charged groups of diphytanoyl phosphatidylserine (DPhPS) lipid. The corresponding effective pKa’s are consistent with the model pKa’s of the acidic residues candidates for titration. Second, the change of channel conductance with salt concentration reveals two distinct regimes (Donnan-controlled electrodiffusion and bulk-like electrodiffusion) fully compatible with the outcomes of selectivity experiments. Third, by measuring channel conductance in mixtures of neutral diphytanoyl phosphatidylcholine (DPhPC) lipids and negatively charged DPhPS lipids in low and high salt concentrations we conclude that the protein-lipid conformation in the channel is likely the same in charged and neutral lipids. Overall, the whole set of experiments supports the proteolipidic structure of SARS-CoV E channels and explains the large difference in channel conductance observed between neutral and charged membranes.",,"['Verdiá-Báguena, Carmina', 'Nieto-Torres, José L.', 'Alcaraz, Antonio', 'DeDiego, Marta L.', 'Enjuanes, Luis', 'Aguilella, Vicente M.']",,,,
,PMC,Cytokine Synergy: an underappreciated contributor to innate anti-viral immunity,http://dx.doi.org/10.1016/j.cyto.2013.04.036,PMC3748162,,,"Inflammatory cytokines, such as tumor necrosis factor and the members of the interferon family, are potent mediators of the innate anti-viral immune response. The intracellular anti-viral states resulting from treatment of cultured cells with each of these molecules independently has been well studied; but, within complex tissues, the early inflammatory response is likely mediated by simultaneously expressed mixures of these, and other, protective anti-viral cytokines. Such cytokine mixtures have been shown to induce potently synergistic anti-viral responses in vitro which are more complex than the simple summation of the individual cytokine response profiles. The physiological role of this ‘cytokine synergy’, however, remains largely unappreciated in vivo. This brief commentary will attempt to summarize the potential effects and mechanisms of anti-viral cytokine synergy as well as present several ‘real-world’ applications where this phenomenon might play an important role.",,"['Bartee, Eric', 'McFadden, Grant']",,,,
,PMC,Accurate Structure Prediction of Peptide-MHC Complexes for Identifying Highly Immunogenic Antigens,http://dx.doi.org/10.1016/j.molimm.2013.04.011,PMC3686981,,,"Designing an optimal HIV-1 vaccine faces the challenge of identifying antigens that induce a broad immune capacity. One factor to control the breadth of T cell responses is the surface morphology of a peptide-MHC complex. Here, we present an in silico protocol for predicting peptide-MHC structure. A robust signature of a conformational transition was identified during all-atom molecular dynamics, which results in a model with high accuracy. A large test set was used in constructing our protocol and we went another step further using a blind test with a wild-type peptide and two highly immunogenic mutants, which predicted substantial conformational changes in both mutants. The center residues at position five of the analogs were configured to be accessible to solvent, forming a prominent surface, while the residue of the wild-type peptide was to point laterally towards the side of the binding cleft. We then experimentally determined the structures of the blind test set, using high resolution of X-ray crystallography, which verified predicted conformational changes. Our observation strongly supports a positive association of the surface morphology of a peptide-MHC complex to its immunogenicity. Our study offers the prospect of enhancing immunogenicity of vaccines by identifying MHC binding immunogens.",,"['Park, Min-Sun', 'Park, Sung Yong', 'Miller, Keith R.', 'Collins, Edward J.', 'Lee, Ha Youn']",,,,
,PMC,"One world, one health: Humans, animals and the environment are inextricably linked—a fact that needs to be remembered and exploited in our modern approach to health",http://dx.doi.org/10.1038/embor.2013.61,PMC3674448,,,"From the point of view that all organisms and the environment share one health, expending effort to address the needs of animals and ecosystems might pay better dividends for human health in the longer term.",,"['van Helden, Paul D', 'van Helden, Lesley S', 'Hoal, Eileen G']",,,,
,PMC,Molecular epidemiology of respiratory syncytial virus transmission in childcare,http://dx.doi.org/10.1016/j.jcv.2013.04.011,PMC3800193,,,"BACKGROUND: Respiratory syncytial virus (RSV) is the most important cause of serious respiratory infections in young children. No prior studies using molecular techniques to examine RSV transmission in the community childcare setting have been performed. OBJECTIVES: We seek to characterize the molecular epidemiology of RSV transmission in childcare to evaluate the impact of RSV disease in a community-based population. METHODS: We sequenced RSV-positive nasopharyngeal samples from a prospective longitudinal study of respiratory illnesses among children enrolled in childcare during three winter seasons. Phylogenetic analysis was performed to identify unique viral strains. RESULTS: RSV was detected in 59 (11%) illnesses. Compared to RSV-negative illnesses, RSV-positive illnesses were associated with longer symptom duration and increased frequency of health care visits. Another respiratory virus was detected in 42 (71%) RSV-positive illnesses. RSV viral load did not differ between RSV-positive illnesses with and without another respiratory virus identified (P = 0.38). In two childcare rooms, 50% of the children had RSV detected within six days of the first case. Five (38%) of 13 illness episodes from one childcare room were sequenced and shown to be the same viral strain, suggesting rapid child-to-child transmission within the room over a 16 day period. CONCLUSIONS: RSV is rapidly transmitted within childcare. Childcare facilities may serve as ideal sites for evaluation of new prevention strategies given the high burden of RSV disease in this population and the rapidity of RSV spread between children.",,"['Chu, Helen Y.', 'Kuypers, Jane', 'Renaud, Christian', 'Wald, Anna', 'Martin, Emily', 'Fairchok, Mary', 'Magaret, Amalia', 'Sarancino, Misty', 'Englund, Janet A.']",,,,
,PMC,Functional analysis of the stem loop S3 and S4 structures in the coronavirus 3'UTR,http://dx.doi.org/10.1016/j.virol.2013.04.021,PMC3700632,,,"We designed a series of mutations to separately destabilize two helical stems (designated S3 and S4) predicted by a covariation-based model of the coronavirus 3'UTR (Zust et al., 2008). Mouse hepatitis virus genomes containing three or four nucleotide mutations that destabilize either S3 or S4 were viable, whereas genomes carrying these mutations in both S3 and S4 were not viable. A genome carrying these mutations in S3 and S4 plus compensatory mutations restoring base-pairing yielded a virus with wild type phenotype. Larger mutations which completely disrupt S3 or S4 generated various phenotypes. Mutations opening up S3 were lethal. Disruptions of S4 generated both viable and lethal mutants. Genomes carrying the original mutations in S3 or S4 plus compensatory mutations restoring base pairing were viable and had robust growth phenotypes. These results support the Zust model for the coronavirus 3'UTR and suggest that the S3 stem is required for virus viability.",,"['Liu, Pinghua', 'Yang, Dong', 'Carter, Kristen', 'Masud, Faryal', 'Leibowitz, Julian L.']",,,,
,PMC,"Macrocyclic Inhibitors of 3C and 3C-like Proteases of Picornavirus, Norovirus, and Coronavirus",http://dx.doi.org/10.1016/j.bmcl.2013.05.021,PMC3750990,,,"The design, synthesis, and in vitro evaluation of the first macrocyclic inhibitor of 3C and 3C-like proteases of picornavirus, norovirus, and coronavirus are reported. The in vitro inhibitory activity (50% effective concentration) of the macrocyclic inhibitor toward enterovirus 3C protease (CVB3 Nancy strain), and coronavirus (SARS-CoV) and norovirus 3C-like proteases, was determined to be 1.8, 15.5 and 5.1 μM, respectively.",,"['Mandadapu, Sivakoteswara Rao', 'Weerawarna, Pathum M.', 'Prior, Allan M.', 'Uy, Roxanne Adeline Z.', 'Aravapalli, Sridhar', 'Alliston, Kevin R.', 'Lushington, Gerald H.', 'Kim, Yunjeong', 'Hua, Duy H.', 'Chang, Kyeong-Ok', 'Groutas, William C.']",,,,
,PMC,Low Serum 25-Hydroxyvitamin D Level and Risk of Upper Respiratory Tract Infection in Children and Adolescents,http://dx.doi.org/10.1093/cid/cit289,PMC3888147,,,"Background. Vitamin D may be important for immune function. Studies to date have shown an inconsistent association between vitamin D and infection with respiratory viruses. The purpose of this study was to determine if serum 25-hydroxyvitamin D (25(OH)D) was associated with laboratory-confirmed viral respiratory tract infections (RTIs) in children. Methods. Serum 25(OH)D levels were measured at baseline and children from Canadian Hutterite communities were followed prospectively during the respiratory virus season. Nasopharyngeal specimens were obtained if symptoms developed and infections were confirmed using polymerase chain reaction. The association between serum 25(OH)D and time to laboratory-confirmed viral RTI was evaluated using a Cox proportional hazards model. Results. Seven hundred forty-three children aged 3–15 years were followed between 22 December 2008 and 23 June 2009. The median serum 25(OH)D level was 62.0 nmol/L (interquartile range, 51.0–74.0). A total of 229 participants (31%) developed at least 1 laboratory-confirmed viral RTI. Younger age and lower serum 25(OH)D levels were associated with increased risk of viral RTI. Serum 25(OH)D levels <75 nmol/L increased the risk of viral RTI by 50% (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.10–2.07, P = .011) and levels <50 nmol/L increased the risk by 70% (HR, 1.67; 95% CI, 1.16–2.40, P = .006). Conclusions. Lower serum 25(OH)D levels were associated with increased risk of laboratory-confirmed viral RTI in children from Canadian Hutterite communities. Interventional studies evaluating the role of vitamin D supplementation to reduce the burden of viral RTIs are warranted.",,"['Science, Michelle', 'Maguire, Jonathon L.', 'Russell, Margaret L.', 'Smieja, Marek', 'Walter, Stephen D.', 'Loeb, Mark']",,,,
,PMC,New coronavirus with “pandemic potential” sparks global surveillance efforts,http://dx.doi.org/10.1503/cmaj.109-4453,PMC3652956,,,,,"Brown, Carolyn",,,,
,PMC,Experts split on adequacy of surveillance since SARS,http://dx.doi.org/10.1503/cmaj.109-4449,PMC3652934,,,,,"Christopher, Paul",,,,
,PMC,Zoonosis emergence linked to agricultural intensification and environmental change,http://dx.doi.org/10.1073/pnas.1208059110,PMC3666729,,,"A systematic review was conducted by a multidisciplinary team to analyze qualitatively best available scientific evidence on the effect of agricultural intensification and environmental changes on the risk of zoonoses for which there are epidemiological interactions between wildlife and livestock. The study found several examples in which agricultural intensification and/or environmental change were associated with an increased risk of zoonotic disease emergence, driven by the impact of an expanding human population and changing human behavior on the environment. We conclude that the rate of future zoonotic disease emergence or reemergence will be closely linked to the evolution of the agriculture–environment nexus. However, available research inadequately addresses the complexity and interrelatedness of environmental, biological, economic, and social dimensions of zoonotic pathogen emergence, which significantly limits our ability to predict, prevent, and respond to zoonotic disease emergence.",,"['Jones, Bryony A.', 'Grace, Delia', 'Kock, Richard', 'Alonso, Silvia', 'Rushton, Jonathan', 'Said, Mohammed Y.', 'McKeever, Declan', 'Mutua, Florence', 'Young, Jarrah', 'McDermott, John', 'Pfeiffer, Dirk Udo']",,,,
,PMC,Architecture and biogenesis of plus-strand RNA virus replication factories,http://dx.doi.org/10.5501/wjv.v2.i2.32,PMC3785047,,,"Plus-strand RNA virus replication occurs in tight association with cytoplasmic host cell membranes. Both, viral and cellular factors cooperatively generate distinct organelle-like structures, designated viral replication factories. This compartmentalization allows coordination of the different steps of the viral replication cycle, highly efficient genome replication and protection of the viral RNA from cellular defense mechanisms. Electron tomography studies conducted during the last couple of years revealed the three dimensional structure of numerous plus-strand RNA virus replication compartments and highlight morphological analogies between different virus families. Based on the morphology of virus-induced membrane rearrangements, we propose two separate subclasses: the invaginated vesicle/spherule type and the double membrane vesicle type. This review discusses common themes and distinct differences in the architecture of plus-strand RNA virus-induced membrane alterations and summarizes recent progress that has been made in understanding the complex interplay between viral and co-opted cellular factors in biogenesis and maintenance of plus-strand RNA virus replication factories.",,"['Paul, David', 'Bartenschlager, Ralf']",,,,
,PMC,Direct Expression and Validation of Phage-selected Peptide Variants in Mammalian Cells,http://dx.doi.org/10.1074/jbc.M113.452839,PMC3696656,,,"Phage display is a key technology for the identification and maturation of high affinity peptides, antibodies, and other proteins. However, limitations of bacterial expression restrict the range and sensitivity of assays that can be used to evaluate phage-selected variants. To address this problem, selected genes are typically transferred to mammalian expression vectors, a major rate-limiting step in the iterative improvement of peptides and proteins. Here we describe a system that combines phage display and efficient mammalian expression in a single vector, pDQ1. This system permits immediate expression of phage-selected genes as IgG1-Fc fusions in mammalian cells, facilitating the rapid, sensitive characterization of a large number of library outputs for their biochemical and functional properties. We demonstrate the utility of this system by improving the ability of a CD4-mimetic peptide to bind the HIV-1 envelope glycoprotein and neutralize HIV-1 entry. We further improved the potency of the resulting peptide, CD4mim6, by limiting its ability to induce the CD4-bound conformation of the envelope glycoprotein. Thus, CD4mim6 and its variants can be used to investigate the properties of the HIV-1 envelope glycoprotein, and pDQ1 can accelerate the discovery of new peptides and proteins through phage display.",,"['Quinlan, Brian D.', 'Gardner, Matthew R.', 'Joshi, Vinita R.', 'Chiang, Jessica J.', 'Farzan, Michael']",,,,
,PMC,Cellular Self-Defense: How Cell-Autonomous Immunity Protects Against Pathogens,http://dx.doi.org/10.1126/science.1233028,PMC3863583,,,"Our prevailing view of vertebrate host defense is strongly shaped by the notion of a specialized set of immune cells as sole guardians of antimicrobial resistance. Yet this view greatly underestimates a capacity for most cell lineages—the majority of which fall outside the traditional province of the immune system—to defend themselves against infection. This ancient and ubiquitous form of host protection is termed cell-autonomous immunity and operates across all three domains of life. Here, we discuss the organizing principles that govern cellular self-defense and how intracellular compartmentalization has shaped its activities to provide effective protection against a wide variety of microbial pathogens.",,"['Randow, Felix', 'MacMicking, John D.', 'James, Leo C.']",,,,
,PMC,Bacterial Complications of Respiratory Tract Viral Illness: A Comprehensive Evaluation,http://dx.doi.org/10.1093/infdis/jit190,PMC3699009,,,"Background. Respiratory tract infection is one of the most common reasons for hospitalization among adults, and recent evidence suggests that many of these illnesses are associated with viruses. Although bacterial infection is known to complicate viral infections, the frequency and impact of mixed viral-bacterial infections has not been well studied. Methods. Adults hospitalized with respiratory illness during 3 winters underwent comprehensive viral and bacterial testing. This assessment was augmented by measuring the serum level of procalcitonin (PCT) as a marker of bacterial infection. Mixed viral-bacterial infection was defined as a positive viral test result plus a positive bacterial assay result or a serum PCT level of ≥ 0.25 ng/mL on admission or day 2 of hospitalization. Results. Of 842 hospitalizations (771 patients) evaluated, 348 (41%) had evidence of viral infection. A total of 212 hospitalizations (61%) involved patients with viral infection alone. Of the remaining 136 hospitalizations (39%) involving viral infection, results of bacterial tests were positive in 64 (18%), and PCT analysis identified bacterial infection in an additional 72 (21%). Subjects hospitalized with mixed viral-bacterial infections were older and more commonly received a diagnosis of pneumonia. Over 90% of hospitalizations in both groups involved subjects who received antibiotics. Notably, 4 of 10 deaths among subjects hospitalized with viral infection alone were secondary to complications of Clostridium difficile colitis. Conclusions. Bacterial coinfection is associated with approximately 40% of viral respiratory tract infections requiring hospitalization. Patients with positive results of viral tests should be carefully evaluated for concomitant bacterial infection. Early empirical antibiotic therapy for patients with an unstable condition is appropriate but is not without risk.",,"['Falsey, Ann R.', 'Becker, Kenneth L.', 'Swinburne, Andrew J.', 'Nylen, Eric S.', 'Formica, Maria A.', 'Hennessey, Patricia A.', 'Criddle, Mary M.', 'Peterson, Derick R.', 'Baran, Andrea', 'Walsh, Edward E.']",,,,
,PMC,"PD-L1/B7-H1 regulates the survival, but not the function of CD8(+) T cells in HSV-1 latently infected Trigeminal Ganglia()",http://dx.doi.org/10.4049/jimmunol.1300582,PMC3679223,,,"Herpes simplex virus type 1 (HSV)-specific CD8(+) T cells provide immunosurveillance of trigeminal ganglion (TG) neurons that harbor latent HSV-1. In C57BL/6 mice the TG-resident CD8(+) T cells are HSV-specific and maintain a 1:1 ratio of cells recognizing an immunodominant epitope on viral glycoprotein B (gB(498–505)-Tet(+)) and cells reactive to subdominant epitopes (gB-Tet(−)). The gB-Tet(−) CD8(+) T cells maintain their frequency in TG by balancing a higher rate of proliferation with a correspondingly higher rate of apoptosis. The increased apoptosis is associated with higher expression of Programmed Death-1 (PD-1) on gB-Tet(−) CD8(+) T cells, and the interaction with PD-1 ligand (PD-L1/B7H1). IFN-γ regulated expression of the PD-1 ligand (PD-L1/B7H1) on neurons bearing higher copies of latent viral genome. In latently infected TG of B7H1(−/−) mice, the number and frequency of PD-1(+) gB-Tet(−) CD8(+) T cells increases dramatically, but gB-Tet(−) CD8(+) T cells remain largely non-functional, and do not provide increased protection from HSV-1 reactivation in ex vivo cultures of latently infected TG. Unlike observations in some chronic infection models, B7H1 blockade did not increase the function of exhausted gB-Tet(−) CD8 T cells in latently infected TG.",,"['Jeon, Sohyun', 'St Leger, Anthony J.', 'Cherpes, Thomas L.', 'Sheridan, Brian S.', 'Hendricks, Robert L.']",,,,
,PMC,In Silico Screening on the Three-dimensional Model of the Plasmodium vivax SUB1 Protease Leads to the Validation of a Novel Anti-parasite Compound,http://dx.doi.org/10.1074/jbc.M113.456764,PMC3689996,,,"Widespread drug resistance calls for the urgent development of new antimalarials that target novel steps in the life cycle of Plasmodium falciparum and Plasmodium vivax. The essential subtilisin-like serine protease SUB1 of Plasmodium merozoites plays a dual role in egress from and invasion into host erythrocytes. It belongs to a new generation of attractive drug targets against which specific potent inhibitors are actively searched. We characterize here the P. vivax SUB1 enzyme and show that it displays a typical auto-processing pattern and apical localization in P. vivax merozoites. To search for small PvSUB1 inhibitors, we took advantage of the similarity of SUB1 with bacterial subtilisins and generated P. vivax SUB1 three-dimensional models. The structure-based virtual screening of a large commercial chemical compounds library identified 306 virtual best hits, of which 37 were experimentally confirmed inhibitors and 5 had K(i) values of <50 μm for PvSUB1. Interestingly, they belong to different chemical families. The most promising competitive inhibitor of PvSUB1 (compound 2) was equally active on PfSUB1 and displayed anti-P. falciparum and Plasmodium berghei activity in vitro and in vivo, respectively. Compound 2 inhibited the endogenous PfSUB1 as illustrated by the inhibited maturation of its natural substrate PfSERA5 and inhibited parasite egress and subsequent erythrocyte invasion. These data indicate that the strategy of in silico screening of three-dimensional models to select for virtual inhibitors combined with stringent biological validation successfully identified several inhibitors of the PvSUB1 enzyme. The most promising hit proved to be a potent cross-inhibitor of PlasmodiumSUB1, laying the groundwork for the development of a globally active small compound antimalarial.",,"['Bouillon, Anthony', 'Giganti, David', 'Benedet, Christophe', 'Gorgette, Olivier', 'Pêtres, Stéphane', 'Crublet, Elodie', 'Girard-Blanc, Christine', 'Witkowski, Benoit', 'Ménard, Didier', 'Nilges, Michael', 'Mercereau-Puijalon, Odile', 'Stoven, Véronique', 'Barale, Jean-Christophe']",,,,
,PMC,"PPARγ signaling and metabolism: the good, the bad and the future",http://dx.doi.org/10.1038/nm.3159,PMC3870016,,,"Thiazolidinediones (TZDs) are potent insulin sensitizers that act through the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) and are highly effective oral medications for type 2 diabetes. However, their unique benefits are shadowed by the risk for fluid retention, weight gain, bone loss and congestive heart failure. This raises the question as to whether it is possible to build a safer generation of PPARγ-specific drugs that evoke fewer side effects while preserving insulin-sensitizing potential. Recent studies that have supported the continuing physiologic and therapeutic relevance of the PPARγ pathway also provide opportunities to develop newer classes of molecules that reduce or eliminate adverse effects. This review highlights key advances in understanding PPARγ signaling in energy homeostasis and metabolic disease and also provides new explanations for adverse events linked to TZD-based therapy.",,"['Ahmadian, Maryam', 'Suh, Jae Myoung', 'Hah, Nasun', 'Liddle, Christopher', 'Atkins, Annette R', 'Downes, Michael', 'Evans, Ronald M']",,,,
,PMC,An Ubiquitin-like Motif in ASK1 Mediates its Association with and Inhibition of the Proteasome,,PMC3839862,,,"Linear polyubiquitin is processed at LRLRGG sequences by deubiquitinating enzymes to make free monomeric ubiquitin. This LRLRGG ubiquitin-like motif is found in a limited number of mammalian non-ubiquitin proteins, including the MAP3K Apoptosis Signal-Regulating Kinase-1 (ASK1), which activates MAPK signaling pathways. The c-terminus of ASK1 binds to the 19S cap of the proteasome allowing ASK1 to phosphorylate and inhibit proteasomal activity. We investigated whether the ubiquitin-like sequence in the c-terminus of ASK1 mediates its association with and inhibition of the proteasome. To test this we generated ASK1 with substitutions or deletions in this ubiquitin-like domain and examined the activation of cellular signaling and the association of ASK1 with the 19S cap of the proteasome. We show that ASK1 mutants have reduced association with the 19S cap of the proteasome, reduced capacity to inhibit the proteasome, and diminished ability to inhibit TNF-induced NF-κB activation. Mutant forms of ASK1 also had reduced capacity to activate JNK signaling, suggesting that the ubiquitin-like motif in ASK1 is also important for coordinating the balance between JNK and NF-κB signaling. Together these results demonstrate that the ubiquitin-like sequence of ASK1 is important for binding to and inhibition of the proteasome, and for the coordinated activation of cellular NF-κB and JNK signaling.",,"['Schneider, Jeffrey R.', 'Lodolce, James P.', 'Boone, David L.']",,,,
,PMC,Interferon-inducible Transmembrane Protein 3 (IFITM3) Restricts Reovirus Cell Entry,http://dx.doi.org/10.1074/jbc.M112.438515,PMC3682530,,,"Reoviruses are double-stranded RNA viruses that infect the mammalian respiratory and gastrointestinal tract. Reovirus infection elicits production of type I interferons (IFNs), which trigger antiviral pathways through the induction of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified, the functions of many of these genes are unknown. The interferon-inducible transmembrane (IFITM) proteins are one class of ISGs that restrict the cell entry of some enveloped viruses, including influenza A virus. One family member, IFITM3, localizes to late endosomes, where reoviruses undergo proteolytic disassembly; therefore, we sought to determine whether IFITM3 also restricts reovirus entry. IFITM3-expressing cell lines were less susceptible to infection by reovirus, as they exhibited significantly lower percentages of infected cells in comparison to control cells. Reovirus replication was also significantly reduced in IFITM3-expressing cells. Additionally, cells expressing an shRNA targeting IFITM3 exhibited a smaller decrease in infection after IFN treatment than the control cells, indicating that endogenous IFITM3 restricts reovirus infection. However, IFITM3 did not restrict entry of reovirus infectious subvirion particles (ISVPs), which do not require endosomal proteolysis, indicating that restriction occurs in the endocytic pathway. Proteolysis of outer capsid protein μ1 was delayed in IFITM3-expressing cells in comparison to control cells, suggesting that IFITM3 modulates the function of late endosomal compartments either by reducing the activity of endosomal proteases or delaying the proteolytic processing of virions. These data provide the first evidence that IFITM3 restricts infection by a nonenveloped virus and suggest that IFITM3 targets an increasing number of viruses through a shared requirement for endosomes during cell entry.",,"['Anafu, Amanda A.', 'Bowen, Christopher H.', 'Chin, Christopher R.', 'Brass, Abraham L.', 'Holm, Geoffrey H.']",,,,
,PMC,Complex history of the amphibian-killing chytrid fungus revealed with genome resequencing data,http://dx.doi.org/10.1073/pnas.1300130110,PMC3677446,,,"Understanding the evolutionary history of microbial pathogens is critical for mitigating the impacts of emerging infectious diseases on economically and ecologically important host species. We used a genome resequencing approach to resolve the evolutionary history of an important microbial pathogen, the chytrid Batrachochytrium dendrobatidis (Bd), which has been implicated in amphibian declines worldwide. We sequenced the genomes of 29 isolates of Bd from around the world, with an emphasis on North, Central, and South America because of the devastating effect that Bd has had on amphibian populations in the New World. We found a substantial amount of evolutionary complexity in Bd with deep phylogenetic diversity that predates observed global amphibian declines. By investigating the entire genome, we found that even the most recently evolved Bd clade (termed the global panzootic lineage) contained more genetic variation than previously reported. We also found dramatic differences among isolates and among genomic regions in chromosomal copy number and patterns of heterozygosity, suggesting complex and heterogeneous genome dynamics. Finally, we report evidence for selection acting on the Bd genome, supporting the hypothesis that protease genes are important in evolutionary transitions in this group. Bd is considered an emerging pathogen because of its recent effects on amphibians, but our data indicate that it has a complex evolutionary history that predates recent disease outbreaks. Therefore, it is important to consider the contemporary effects of Bd in a broader evolutionary context and identify specific mechanisms that may have led to shifts in virulence in this system.",,"['Rosenblum, Erica Bree', 'James, Timothy Y.', 'Zamudio, Kelly R.', 'Poorten, Thomas J.', 'Ilut, Dan', 'Rodriguez, David', 'Eastman, Jonathan M.', 'Richards-Hrdlicka, Katy', 'Joneson, Suzanne', 'Jenkinson, Thomas S.', 'Longcore, Joyce E.', 'Parra Olea, Gabriela', 'Toledo, Luís Felipe', 'Arellano, Maria Luz', 'Medina, Edgar M.', 'Restrepo, Silvia', 'Flechas, Sandra Victoria', 'Berger, Lee', 'Briggs, Cheryl J.', 'Stajich, Jason E.']",,,,
,PMC,Modeling epidemic spread with awareness and heterogeneous transmission rates in networks,http://dx.doi.org/10.1007/s10867-013-9318-8,PMC3689355,,,"During an epidemic outbreak in a human population, susceptibility to infection can be reduced by raising awareness of the disease. In this paper, we investigate the effects of three forms of awareness (i.e., contact, local, and global) on the spread of a disease in a random network. Connectivity-correlated transmission rates are assumed. By using the mean-field theory and numerical simulation, we show that both local and contact awareness can raise the epidemic thresholds while the global awareness cannot, which mirrors the recent results of Wu et al. The obtained results point out that individual behaviors in the presence of an infectious disease has a great influence on the epidemic dynamics. Our method enriches mean-field analysis in epidemic models.",,"Shang, Yilun",,,,
,PMC,Relative Antioxidant Activities of Quercetin and Its Structurally Related Substances and Their Effects on NF-κB/CRE/AP-1 Signaling in Murine Macrophages,http://dx.doi.org/10.1007/s10059-013-0031-z,PMC3887868,,,"Reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by the oxidative burst in activated macrophages and neutrophils cause oxidative stress-implicated diseases. Quercetin is flavonoid that occurs naturally in plants and is widely used as a nutritional supplement due to its antioxidant and anti-inflammatory properties. In this study, we investigated antioxidant activities and mechanisms of action in zymosan-induced macrophages of quercetin and quercetin-related flavonoids such as quercitrin, isoquercitrin, quercetin 3-O-β-(2″-galloyl)-rhamnopyranoside (QGR) and quercetin 3-O-β-(2″-galloyl)-glucopyranoside (QGG) as well as gallic acid, a building moiety of QGR and QGG. QGR and QGG exhibited stronger antioxidant activities compared with quercetin, whereas quercitrin, isoquercitrin and gallic acid exhibited weak-to-no antioxidant activities, assessed by 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging, superoxide production, superoxide scavenging, nitric oxide (NO) production, peroxynitrite (ONOO(−)) scavenging and myeloperoxidase (MPO) activity. Regarding mechanisms, the quercetin-containing flavonoids QGR and QGG differentially targeted compared with quercetin in the NF-κB signaling pathway that inhibited the DNA binding activity of the NF-κB complex without affecting the degradation and phosphorylation of IκBα and NF-κB phosphorylation. In addition, QGR and QGG inhibited CRE and activator protein (AP-1) transcriptional activity and JNK phosphorylation by inhibiting the cAMP/protein kinase A (PKA) and protein kinase C (PKC) signaling in a different manner than quercetin. Our results showed that although QGR and QGG exhibited stronger antioxidant activities than quercetin in macrophages, their mechanisms of action in terms of the NF-κB, PKA and PKC signaling pathways were different.",,"['Kim, Byung-Hak', 'Choi, Jung Sook', 'Yi, Eun Hee', 'Lee, Jin-Ku', 'Won, Cheolhee', 'Ye, Sang-Kyu', 'Kim, Myoung-Hwan']",,,,
,PMC,A Cluster of Primary Pneumonic Plague Transmitted in a Truck Cab in a New Enzootic Focus in China,http://dx.doi.org/10.4269/ajtmh.12-0163,PMC3752759,,,"We investigated a cluster of five cases of severe pneumonia from one village in Yunnan Province, China. We searched for severe pneumonia in the village and hospitals. We interviewed patients and family members about exposures. We tested acute and convalescent sera for antigen and antibody of severe acute respiratory syndrome, avian influenza, and plague. The only common exposure of the five patients was riding together in the enclosed cab of a truck for 1.5 hours while taking the first patient to the hospital. Seroconversion to plague F1 antigen confirmed plague in three survivors. Unfamiliarity of clinicians with plague and lack of sputum examination, blood culture, or postmortem examination delayed the diagnosis. No plague cases occurred among family and village contacts and health care workers. High infectivity in this cluster was limited to a crowded, poorly ventilated truck.",,"['Luo, Huiming', 'Dong, Xingqi', 'Li, Furong', 'Xie, Xu', 'Song, Zhizhong', 'Shao, Zhujun', 'Li, Zhongjie', 'Tong, Zhaohui', 'Wang, Guangfa', 'Zhang, Hongtao', 'Yang, Tielong', 'He, Gao', 'He, Zeyuan', 'Fontaine, Robert E.', 'Zeng, Guang']",,,,
,PMC,Quantifying the Antibody Binding on Protein Microarrays using Microarray Nonlinear Calibration,http://dx.doi.org/10.2144/000114028,PMC4477631,,,"To address the issue of quantification for antibody assays with protein microarrays, we firstly developed a Microarray Nonlinear Calibration (MiNC) method that applies in the quantification of antibody binding to the surface of microarray spots. We found that MiNC significantly increased the linear dynamic range and reduced assay variations. A serological analysis of guinea pig Mycobacterium tuberculosis models showed that a larger number of putative antigen targets were identified with MiNC, which is consistent with the improved assay performance of protein microarrays. We expect that our cumulative results will provide scientists with a new appreciation of antibody assays with protein microarrays. Our MiNC method has the potential to be employed in biomedical research with multiplex antibody assays which need quantitation, including the discovery of antibody biomarkers, clinical diagnostics with multi-antibody signatures and construction of immune mathematical models.",,"['Yu, Xiaobo', 'Wallstrom, Garrick', 'Magee, Dewey Mitchell', 'Qiu, Ji', 'Mendoza, D. Eliseo A.', 'Wang, Jie', 'Bian, Xiaofang', 'Graves, Morgan', 'LaBaer, Joshua']",,,,
,PMC,Public Health Watch,http://dx.doi.org/10.1177/1715163513488330,PMC3676221,,,,,"Lynas, Kathie",,,,
,PMC,Influenza infection screening tools fail to accurately predict influenza status for hospitalized patients during pandemic H1N1 influenza season,,PMC3814272,,,"BACKGROUND: Following the severe acute respiratory syndrome outbreak in 2003, hospitals have been mandated to use infection screening questionnaires to determine which patients have infectious respiratory illness and, therefore, require isolation precautions. Despite widespread use of symptom-based screening tools in Ontario, there are no data supporting the accuracy of these screening tools in hospitalized patients. OBJECTIVE: To measure the performance characteristics of infection screening tools used during the H1N1 influenza season. METHODS: The present retrospective cohort study was conducted at The Ottawa Hospital (Ottawa, Ontario) between October and December, 2009. Consecutive inpatients admitted from the emergency department were included if they were ≥18 years of age, underwent a screening tool assessment at presentation and had a most responsible diagnosis that was cardiac, respiratory or infectious. The gold-standard outcome was laboratory diagnosis of influenza. RESULTS: The prevalence of laboratory-confirmed influenza was 23.5%. The sensitivity and specificity of the febrile respiratory illness screening tool were 74.5% (95% CI 60.5% to 84.8%) and 32.7% (95% CI 25.8% to 40.5%), respectively. The sensitivity and specificity of the influenza-like illness screening tool were 75.6% (95% CI 61.3% to 85.8%) and 46.3% (95% CI 38.2% to 54.7%), respectively. CONCLUSIONS: The febrile respiratory illness screening tool missed 26% of active influenza cases, while 67% of noninfluenza patients were unnecessarily placed under respiratory isolation. Results of the present study suggest that infection-control practitioners should re-evaluate their strategy of screening patients at admission for contagious respiratory illness using symptom- and sign-based tests. Future efforts should focus on the derivation and validation of clinical decision rules that combine clinical features with laboratory tests.",,"['Mulpuru, Sunita', 'Roth, Virginia R', 'Lawrence, Nadine', 'Forster, Alan J']",,,,
,PMC,Quiz Corner,,PMC3624910,,,,,,,,,
,PMC,Application of mass spectrometry to molecular diagnostics of viral infections,http://dx.doi.org/10.1586/erm.13.24,PMC5831079,,,"Mass spectrometry (MS) has found numerous applications in life sciences. It has high accuracy, sensitivity and wide dynamic range in addition to medium- to high-throughput capabilities. These features make MS a superior platform for analysis of various biomolecules including proteins, lipids, nucleic acids and carbohydrates. Until recently, MS was applied for protein detection and characterization. During the last decade, however, MS has successfully been used for molecular diagnostics of microbial and viral infections with the most notable applications being identification of pathogens, genomic sequencing, mutation detection, DNA methylation analysis, tracking of transmissions, and characterization of genetic heterogeneity. These new developments vastly expand the MS application from experimental research to public health and clinical fields. Matching of molecular techniques with specific requirements of the major MS platforms has produced powerful technologies for molecular diagnostics, which will further benefit from coupling with computational tools for extracting clinical information from MS-derived data.",,"['Ganova-Raeva, Lilia M', 'Khudyakov, Yury E']",,,,
,PMC,Challenge of N95 Filtering Facepiece Respirators with Viable H1N1 Influenza Aerosols,http://dx.doi.org/10.1086/670225,PMC4646082,,,"OBJECTIVE: Specification of appropriate personal protective equipment for respiratory protection against influenza is somewhat controversial. In a clinical environment, N95 filtering facepiece respirators (FFRs) are often recommended for respiratory protection against infectious aerosols. This study evaluates the ability of N95 FFRs to capture viable H1N1 influenza aerosols. METHODS: Five N95 FFR models were challenged with aerosolized viable H1N1 influenza and inert polystyrene latex particles at continuous flow rates of 85 and 170 liters per minute. Virus was assayed using Madin-Darby canine kidney cells to determine the median tissue culture infective dose (TCID(50)). Aerosols were generated using a Collison nebulizer containing H1N1 influenza virus at 1 × 10(8) TCID(50)/mL. To determine filtration efficiency, viable sampling was performed upstream and downstream of the FFR. RESULTS: N95 FFRs filtered 0.8-µm particles of both H1N1 influenza and inert origins with more than 95% efficiency. With the exception of 1 model, no statistically significant difference in filtration performance was observed between influenza and inert particles of similar size. Although statistically significant differences were observed for 2 models when comparing the 2 flow rates, the differences have no significance to protection. CONCLUSIONS: This study empirically demonstrates that a National Institute for Occupational Safety and Health–approved N95 FFR captures viable H1N1 influenza aerosols as well as or better than its N95 rating, suggesting that a properly fitted FFR reduces inhalation exposure to airborne influenza virus. This study also provides evidence that filtration efficiency is based primarily on particle size rather than the nature of the particle’s origin.",,"['Harnish, Delbert A.', 'Heimbuch, Brian K.', 'Husband, Michael', 'Lumley, April E.', 'Kinney, Kimberly', 'Shaffer, Ronald E.', 'Wander, Joseph D.']",,,,
,PMC,"Clinical manifestations, response to treatment, and clinical outcome for Weimaraners with hypertrophic osteodystrophy: 53 cases (2009–2011)",http://dx.doi.org/10.2460/javma.242.9.1260,PMC4123543,,,"OBJECTIVE: To evaluate clinical manifestations, response to treatment, and outcome for Weimaraners with hypertrophic osteodystrophy (HOD). DESIGN: Retrospective case series. ANIMALS: 53 dogs. PROCEDURES: Medical records were reviewed for signalment, vaccination history, clinical signs, laboratory test results, response to treatment, and relapses. Radiographs were reviewed. RESULTS: Clinical signs included pyrexia, lethargy, and ostealgia; signs involving the gastrointestinal, ocular, or cutaneous systems were detected. Of the 53 dogs, 28 (52.8%) had HOD-affected littermates. Dogs with HOD-affected littermates were more likely to relapse, compared with the likelihood of relapse for dogs with no HOD-affected littermates. All 53 dogs had been vaccinated 1 to 30 days before HOD onset; no difference was found between the number of dogs with a history of vaccination with a recombinant vaccine (n = 21) versus a nonrecombinant vaccine (32). Fifty (94.3%) dogs had radiographic lesions compatible with HOD at disease onset, and the other 3 (5.7%) had HOD lesions 48 to 72 hours after the onset of clinical signs. Twelve of 22 (54.5%) dogs treated with NSAIDs did not achieve remission by 7 days after initiation of treatment. All dogs treated initially with corticosteroids achieved remission within 8 to 48 hours. Of the 33 dogs that reached adulthood, 28 (84.8%) were healthy and 5 (15.2%) had episodes of pyrexia and malaise. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with corticosteroids was superior to treatment with NSAIDs in Weimaraners with HOD. It may be necessary to evaluate repeated radiographs to establish a diagnosis of HOD. Most HOD-affected Weimaraners had resolution of the condition with physeal closure.",,"['Safra, Noa', 'Johnson, Eric G.', 'Lit, Lisa', 'Foreman, Oded', 'Wolf, Zena T.', 'Aguilar, Miriam', 'Karmi, Nili', 'Finno, Carrie J.', 'Bannasch, Danika L.']",,,,
,PMC,PD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8(+) T cells in mice,http://dx.doi.org/10.1172/JCI64704,PMC3668817,,,"Viral vector–based vaccines that induce protective CD8(+) T cell immunity can prevent or control pathogenic SIV infections, but issues of preexisting immunity and safety have impeded their implementation in HIV-1. Here, we report the development of what we believe to be a novel antigen-targeting DNA vaccine strategy that exploits the binding of programmed death-1 (PD1) to its ligands expressed on dendritic cells (DCs) by fusing soluble PD1 with HIV-1 GAG p24 antigen. As compared with non–DC-targeting vaccines, intramuscular immunization via electroporation (EP) of the fusion DNA in mice elicited consistently high frequencies of GAG-specific, broadly reactive, polyfunctional, long-lived, and cytotoxic CD8(+) T cells and robust anti-GAG antibody titers. Vaccination conferred remarkable protection against mucosal challenge with vaccinia GAG viruses. Soluble PD1–based vaccination potentiated CD8(+) T cell responses by enhancing antigen binding and uptake in DCs and activation in the draining lymph node. It also increased IL-12–producing DCs and engaged antigen cross-presentation when compared with anti-DEC205 antibody-mediated DC targeting. The high frequency of durable and protective GAG-specific CD8(+) T cell immunity induced by soluble PD1–based vaccination suggests that PD1-based DNA vaccines could potentially be used against HIV-1 and other pathogens.",,"['Zhou, Jingying', 'Cheung, Allen K.L.', 'Tan, Zhiwu', 'Wang, Haibo', 'Yu, Wenbo', 'Du, Yanhua', 'Kang, Yuanxi', 'Lu, Xiaofan', 'Liu, Li', 'Yuen, Kwok-Yung', 'Chen, Zhiwei']",,,,
,PMC,Electronic Nose Technology for Detection of Invasive Pulmonary Aspergillosis in Prolonged Chemotherapy-Induced Neutropenia: a Proof-of-Principle Study,http://dx.doi.org/10.1128/JCM.02838-12,PMC3647955,,,"Although the high mortality rate of pulmonary invasive aspergillosis (IA) in patients with prolonged chemotherapy-induced neutropenia (PCIN) can be reduced by timely diagnosis, a diagnostic test that reliably detects IA at an early stage is lacking. We hypothesized that an electronic nose (eNose) could fulfill this need. An eNose can discriminate various lung diseases through the analysis of exhaled volatile organic compounds (VOCs). An eNose is cheap and noninvasive and yields results within minutes. In a single-center prospective cohort study, we included patients who were treated with chemotherapy expected to result in PCIN. Based on standardized indications, a full diagnostic workup was performed to confirm invasive aspergillosis or to rule it out. Patients with no aspergillosis were considered controls, and patients with probable or proven aspergillosis were considered index cases. Exhaled breath was examined with a Cyranose 320 (Smith Detections, Pasadena, CA). The resulting data were analyzed using principal component reduction. The primary endpoint was cross-validated diagnostic accuracy, defined as the percentage of patients correctly classified using the leave-one-out method. Accuracy was validated by 100,000 random classifications. We included 46 subjects who underwent 16 diagnostic workups, resulting in 6 cases and 5 controls. The cross-validated accuracy of the eNose in diagnosing IA was 90.9% (P = 0.022; sensitivity, 100%; specificity, 83.3%). Receiver operating characteristic analysis showed an area under the curve of 0.93. These preliminary data indicate that PCIN patients with IA have a distinct exhaled VOC profile that can be detected with eNose technology. The diagnostic accuracy of the eNose for invasive aspergillosis warrants validation.",,"['de Heer, Koen', 'van der Schee, Marc P.', 'Zwinderman, Koos', 'van den Berk, Inge A. H.', 'Visser, Caroline Elisabeth', 'van Oers, Rien', 'Sterk, Peter J.']",,,,
,PMC,"Comparison of the Biofire FilmArray RP, Genmark eSensor RVP, Luminex xTAG RVPv1, and Luminex xTAG RVP Fast Multiplex Assays for Detection of Respiratory Viruses",http://dx.doi.org/10.1128/JCM.03368-12,PMC3647947,,,"There are several U.S. FDA-cleared molecular respiratory virus panels available today, each with advantages and disadvantages. This study compares four multiplex panels, the BioFire Diagnostics FilmArray RP (respiratory panel), the GenMark Dx eSensor RVP (respiratory viral panel), the Luminex xTAG RVPv1, and the Luminex xTAG RVP fast. Three hundred specimens (200 retrospective and 100 consecutive) were tested using all four platforms to determine performance characteristics. The overall sensitivity and specificity, respectively, and 95% confidence interval (CI; in parentheses) for each panel were as follows: FilmArray RP, 84.5% (79.2, 88.6) and 100% (96.2, 100); eSensor RVP, 98.3% (95.5, 99.5) and 99.2% (95.4, 100); xTAG RVPv1, 92.7% (88.5, 95.4) and 99.8% (96.0, 100); and xTAG RVP fast, 84.4% (78.5, 88.9) and 99.9% (96.1, 100). The sensitivity of each assay fluctuated by viral target, with the greatest discrepancies noted for adenovirus and influenza virus B detection. Hands-on time and time to result were recorded and ease of use was assessed to generate a complete profile of each assay.",,"['Popowitch, Elena B.', ""O'Neill, Stacey S."", 'Miller, Melissa B.']",,,,
,PMC,Development of a Pseudotyped-Lentiviral-Vector-Based Neutralization Assay for Chikungunya Virus Infection,http://dx.doi.org/10.1128/JCM.03109-12,PMC3647917,,,"Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes chikungunya fever in Africa, South Asia, and Southeast Asia. Because the mosquito vector Aedes albopictus is present in habitats across Europe, North America, and East Asia, CHIKV has become a serious worldwide public health concern. Infection with CHIKV typically causes fever, rash, myalgia, and arthralgia. One of the important questions yet to be answered is how the host immune system is involved in the development of this disease. In this study, we prepared a CHIKV-pseudotyped lentiviral vector for use in a safe and convenient neutralization (NT) assay and analyzed its efficacy. The CHIKV-pseudotyped lentiviral vector was prepared by cotransfection with plasmids encoding the CHIKV glycoproteins E3, E2, 6k, and E1, packaging elements, and a luciferase reporter. This alternative to native CHIKV can be safely handled in a biosafety level 2 facility. The NT assay was optimized using sera from CHIKV-immunized mice and then applied to human patient sera. The majority of the serum samples from patients with chikungunya in Thailand showed robust neutralization activities, with titers that were tightly correlated with those determined by a conventional NT assay. Moreover, there was a strong correlation with the CHIKV antibody titers as determined by enzyme-linked immunosorbent assay. Thus, the CHIKV-pseudotyped-lentiviral-vector-based NT assay system is a powerful tool for examining the neutralization activity of patient sera, which will lead to a better understanding of the immune responses involved in CHIKV infection.",,"['Kishishita, Natsuko', 'Takeda, Naokazu', 'Anuegoonpipat, Atchareeya', 'Anantapreecha, Surapee']",,,,
,PMC,Coronaviruses in bats from Mexico,http://dx.doi.org/10.1099/vir.0.049759-0,PMC3709589,,,"Bats are reservoirs for a wide range of human pathogens including Nipah, Hendra, rabies, Ebola, Marburg and severe acute respiratory syndrome coronavirus (CoV). The recent implication of a novel beta (β)-CoV as the cause of fatal respiratory disease in the Middle East emphasizes the importance of surveillance for CoVs that have potential to move from bats into the human population. In a screen of 606 bats from 42 different species in Campeche, Chiapas and Mexico City we identified 13 distinct CoVs. Nine were alpha (α)-CoVs; four were β-CoVs. Twelve were novel. Analyses of these viruses in the context of their hosts and ecological habitat indicated that host species is a strong selective driver in CoV evolution, even in allopatric populations separated by significant geographical distance; and that a single species/genus of bat can contain multiple CoVs. A β-CoV with 96.5 % amino acid identity to the β-CoV associated with human disease in the Middle East was found in a Nyctinomops laticaudatus bat, suggesting that efforts to identify the viral reservoir should include surveillance of the bat families Molossidae/Vespertilionidae, or the closely related Nycteridae/Emballonuridae. While it is important to investigate unknown viral diversity in bats, it is also important to remember that the majority of viruses they carry will not pose any clinical risk, and bats should not be stigmatized ubiquitously as significant threats to public health.",,"['Anthony, S. J.', 'Ojeda-Flores, R.', 'Rico-Chávez, O.', 'Navarrete-Macias, I.', 'Zambrana-Torrelio, C. M.', 'Rostal, M. K.', 'Epstein, J. H.', 'Tipps, T.', 'Liang, E.', 'Sanchez-Leon, M.', 'Sotomayor-Bonilla, J.', 'Aguirre, A. A.', 'Ávila-Flores, R.', 'Medellín, R. A.', 'Goldstein, T.', 'Suzán, G.', 'Daszak, P.', 'Lipkin, W. I.']",,,,
,PMC,Mucosal Priming with a Replicating-Vaccinia Virus-Based Vaccine Elicits Protective Immunity to Simian Immunodeficiency Virus Challenge in Rhesus Monkeys,http://dx.doi.org/10.1128/JVI.03247-12,PMC3648167,,,"Mucosal surfaces are not targeted by most human immunodeficiency virus type 1 (HIV-1) vaccines, despite being major routes for HIV-1 transmission. Here we report a novel vaccination regimen consisting of a mucosal prime with a modified replicating vaccinia virus Tiantan strain (MVTT(SIVgpe)) and an intramuscular boost with a nonreplicating adenovirus strain (Ad5(SIVgpe)). This regimen elicited robust cellular immune responses with enhanced magnitudes, sustainability, and polyfunctionality, as well as higher titers of neutralizing antibodies against the simian immunodeficiency virus SIV(mac1A11) in rhesus monkeys. The reductions in peak and set-point viral loads were significant in most animals, with one other animal being protected fully from high-dose intrarectal inoculation of SIV(mac239). Furthermore, the animals vaccinated with this regimen were healthy, while ∼75% of control animals developed simian AIDS. The protective effects correlated with the vaccine-elicited SIV-specific CD8(+) T cell responses against Gag and Pol. Our study provides a novel strategy for developing an HIV-1 vaccine by using the combination of a replicating vector and mucosal priming.",,"['Sun, Caijun', 'Chen, Zhiwei', 'Tang, Xian', 'Zhang, Yinfeng', 'Feng, Liqiang', 'Du, Yanhua', 'Xiao, Lijun', 'Liu, Li', 'Zhu, Weijun', 'Chen, Ling', 'Zhang, Linqi']",,,,
,PMC,Rational Design of a Flavivirus Vaccine by Abolishing Viral RNA 2′-O Methylation,http://dx.doi.org/10.1128/JVI.02806-12,PMC3648161,,,"Viruses that replicate in the cytoplasm cannot access the host nuclear capping machinery. These viruses have evolved viral methyltransferase(s) to methylate N-7 and 2′-O cap of their RNA; alternatively, they “snatch” host mRNA cap to form the 5′ end of viral RNA. The function of 2′-O methylation of viral RNA cap is to mimic cellular mRNA and to evade host innate immune restriction. A cytoplasmic virus defective in 2′-O methylation is replicative, but its viral RNA lacks 2′-O methylation and is recognized and eliminated by the host immune response. Such a mutant virus could be rationally designed as a live attenuated vaccine. Here, we use Japanese encephalitis virus (JEV), an important mosquito-borne flavivirus, to prove this novel vaccine concept. We show that JEV methyltransferase is responsible for both N-7 and 2′-O cap methylations as well as evasion of host innate immune response. Recombinant virus completely defective in 2′-O methylation was stable in cell culture after being passaged for >30 days. The mutant virus was attenuated in mice, elicited robust humoral and cellular immune responses, and retained the engineered mutation in vivo. A single dose of immunization induced full protection against lethal challenge with JEV strains in mice. Mechanistically, the attenuation phenotype was attributed to the enhanced sensitivity of the mutant virus to the antiviral effects of interferon and IFIT proteins. Collectively, the results demonstrate the feasibility of using 2′-O methylation-defective virus as a vaccine approach; this vaccine approach should be applicable to other flaviviruses and nonflaviviruses that encode their own viral 2′-O methyltransferases.",,"['Li, Shi-Hua', 'Dong, Hongping', 'Li, Xiao-Feng', 'Xie, Xuping', 'Zhao, Hui', 'Deng, Yong-Qiang', 'Wang, Xiao-Yu', 'Ye, Qing', 'Zhu, Shun-Ya', 'Wang, Hong-Jiang', 'Zhang, Bo', 'Leng, Qi-Bin', 'Zuest, Roland', 'Qin, E-De', 'Qin, Cheng-Feng', 'Shi, Pei-Yong']",,,,
,PMC,"The Spike Protein of the Emerging Betacoronavirus EMC Uses a Novel Coronavirus Receptor for Entry, Can Be Activated by TMPRSS2, and Is Targeted by Neutralizing Antibodies",http://dx.doi.org/10.1128/JVI.00128-13,PMC3648152,,,"The novel human coronavirus EMC (hCoV-EMC), which recently emerged in Saudi Arabia, is highly pathogenic and could pose a significant threat to public health. The elucidation of hCoV-EMC interactions with host cells is critical to our understanding of the pathogenesis of this virus and to the identification of targets for antiviral intervention. Here we investigated the viral and cellular determinants governing hCoV-EMC entry into host cells. We found that the spike protein of hCoV-EMC (EMC-S) is incorporated into lentiviral particles and mediates transduction of human cell lines derived from different organs, including the lungs, kidneys, and colon, as well as primary human macrophages. Expression of the known coronavirus receptors ACE2, CD13, and CEACAM1 did not facilitate EMC-S-driven transduction, suggesting that hCoV-EMC uses a novel receptor for entry. Directed protease expression and inhibition analyses revealed that TMPRSS2 and endosomal cathepsins activate EMC-S for virus-cell fusion and constitute potential targets for antiviral intervention. Finally, EMC-S-driven transduction was abrogated by serum from an hCoV-EMC-infected patient, indicating that EMC-S-specific neutralizing antibodies can be generated in patients. Collectively, our results indicate that hCoV-EMC uses a novel receptor for protease-activated entry into human cells and might be capable of extrapulmonary spread. In addition, they define TMPRSS2 and cathepsins B and L as potential targets for intervention and suggest that neutralizing antibodies contribute to the control of hCoV-EMC infection.",,"['Gierer, Stefanie', 'Bertram, Stephanie', 'Kaup, Franziska', 'Wrensch, Florian', 'Heurich, Adeline', 'Krämer-Kühl, Annika', 'Welsch, Kathrin', 'Winkler, Michael', 'Meyer, Benjamin', 'Drosten, Christian', 'Dittmer, Ulf', 'von Hahn, Thomas', 'Simmons, Graham', 'Hofmann, Heike', 'Pöhlmann, Stefan']",,,,
,PMC,"1918 Influenza Virus Hemagglutinin (HA) and the Viral RNA Polymerase Complex Enhance Viral Pathogenicity, but Only HA Induces Aberrant Host Responses in Mice",http://dx.doi.org/10.1128/JVI.02753-12,PMC3624330,,,"The 1918 pandemic influenza virus was the most devastating infectious agent in human history, causing fatal pneumonia and an estimated 20 to 50 million deaths worldwide. Previous studies indicated a prominent role of the hemagglutinin (HA) gene in efficient replication and high virulence of the 1918 virus in mice. It is, however, still unclear whether the high replication ability or the 1918 influenza virus HA gene is required for 1918 virus to exhibit high virulence in mice. Here, we examined the biological properties of reassortant viruses between the 1918 virus and a contemporary human H1N1 virus (A/Kawasaki/173/2001 [K173]) in a mouse model. In addition to the 1918 influenza virus HA, we demonstrated the role of the viral RNA replication complex in efficient replication of viruses in mouse lungs, whereas only the HA gene is responsible for lethality in mice. Global gene expression profiling of infected mouse lungs revealed that the 1918 influenza virus HA was sufficient to induce transcriptional changes similar to those induced by the 1918 virus, despite difference in lymphocyte gene expression. Increased expression of genes associated with the acute-phase response and the protein ubiquitination pathway were enriched during infections with the 1918 and 1918HA/K173 viruses, whereas reassortant viruses bearing the 1918 viral RNA polymerase complex induced transcriptional changes similar to those seen with the K173 virus. Taken together, these data suggest that HA and the viral RNA polymerase complex are critical determinants of Spanish influenza pathogenesis, but only HA, and not the viral RNA polymerase complex and NP, is responsible for extreme host responses observed in mice infected with the 1918 influenza virus.",,"['Watanabe, Tokiko', 'Tisoncik-Go, Jennifer', 'Tchitchek, Nicolas', 'Watanabe, Shinji', 'Benecke, Arndt G.', 'Katze, Michael G.', 'Kawaoka, Yoshihiro']",,,,
,PMC,Human Cell Tropism and Innate Immune System Interactions of Human Respiratory Coronavirus EMC Compared to Those of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.03496-12,PMC3624328,,,"Infections with human coronavirus EMC (HCoV-EMC) are associated with severe pneumonia. We demonstrate that HCoV-EMC resembles severe acute respiratory syndrome coronavirus (SARS-CoV) in productively infecting primary and continuous cells of the human airways and in preventing the induction of interferon regulatory factor 3 (IRF-3)-mediated antiviral alpha/beta interferon (IFN-α/β) responses. However, HCoV-EMC was markedly more sensitive to the antiviral state established by ectopic IFN. Thus, HCoV-EMC can utilize a broad range of human cell substrates and suppress IFN induction, but it does not reach the IFN resistance of SARS-CoV.",,"['Zielecki, Florian', 'Weber, Michaela', 'Eickmann, Markus', 'Spiegelberg, Larissa', 'Zaki, Ali Moh', 'Matrosovich, Mikhail', 'Becker, Stephan', 'Weber, Friedemann']",,,,
,PMC,RNA Helicase Signaling Is Critical for Type I Interferon Production and Protection against Rift Valley Fever Virus during Mucosal Challenge,http://dx.doi.org/10.1128/JVI.01997-12,PMC3624317,,,"Rift Valley fever virus (RVFV) is an emerging RNA virus with devastating economic and social consequences. Clinically, RVFV induces a gamut of symptoms ranging from febrile illness to retinitis, hepatic necrosis, hemorrhagic fever, and death. It is known that type I interferon (IFN) responses can be protective against severe pathology; however, it is unknown which innate immune receptor pathways are crucial for mounting this response. Using both in vitro assays and in vivo mucosal mouse challenge, we demonstrate here that RNA helicases are critical for IFN production by immune cells and that signaling through the helicase adaptor molecule MAVS (mitochondrial antiviral signaling) is protective against mortality and more subtle pathology during RVFV infection. In addition, we demonstrate that Toll-like-receptor-mediated signaling is not involved in IFN production, further emphasizing the importance of the RNA cellular helicases in type I IFN responses to RVFV.",,"['Ermler, Megan E.', 'Yerukhim, Ekaterina', 'Schriewer, Jill', 'Schattgen, Stefan', 'Traylor, Zachary', 'Wespiser, Adam R.', 'Caffrey, Daniel R.', 'Chen, Zhijian J.', 'King, Charles H.', 'Gale, Michael', 'Colonna, Marco', 'Fitzgerald, Katherine A.', 'Buller, R. Mark L.', 'Hise, Amy G.']",,,,
,PMC,Functional Analysis of the Murine Coronavirus Genomic RNA Packaging Signal,http://dx.doi.org/10.1128/JVI.00100-13,PMC3624306,,,"Coronaviruses selectively package genomic RNA into assembled virions, despite the great molar excess of subgenomic RNA species that is present in infected cells. The genomic packaging signal (PS) for the coronavirus mouse hepatitis virus (MHV) was originally identified as an element that conferred packaging capability to defective interfering RNAs. The MHV PS is an RNA structure that maps to the region of the replicase gene encoding the nonstructural protein 15 subunit of the viral replicase-transcriptase complex. To begin to understand the role and mechanism of action of the MHV PS in its native genomic locus, we constructed viral mutants in which this cis-acting element was altered, deleted, or transposed. Our results demonstrated that the PS is pivotal in the selection of viral genomic RNA for incorporation into virions. Mutants in which PS RNA secondary structure was disrupted or entirely ablated packaged large quantities of subgenomic RNAs, in addition to genomic RNA. Moreover, the PS retained its function when displaced to an ectopic site in the genome. Surprisingly, the PS was not essential for MHV viability, nor did its elimination have a severe effect on viral growth. However, the PS was found to provide a distinct selective advantage to MHV. Viruses containing the PS readily outcompeted their otherwise isogenic counterparts lacking the PS.",,"['Kuo, Lili', 'Masters, Paul S.']",,,,
,PMC,Porcine Reproductive and Respiratory Syndrome Virus Nsp1β Inhibits Interferon-Activated JAK/STAT Signal Transduction by Inducing Karyopherin-α1 Degradation,http://dx.doi.org/10.1128/JVI.02643-12,PMC3624296,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) inhibits the interferon-mediated antiviral response. Type I interferons (IFNs) induce the expression of IFN-stimulated genes by activating phosphorylation of both signal transducer and activator of transcription 1 (STAT1) and STAT2, which form heterotrimers (interferon-stimulated gene factor 3 [ISGF3]) with interferon regulatory factor 9 (IRF9) and translocate to the nucleus. PRRSV Nsp1β blocks the nuclear translocation of the ISGF3 complex by an unknown mechanism. In this study, we discovered that Nsp1β induced the degradation of karyopherin-α1 (KPNA1, also called importin-α5), which is known to mediate the nuclear import of ISGF3. Overexpression of Nsp1β resulted in a reduction of KPNA1 levels in a dose-dependent manner, and treatment of the cells with the proteasome inhibitor MG132 restored KPNA1 levels. Furthermore, the presence of Nsp1β induced an elevation of KPNA1 ubiquitination and a shortening of its half-life. Our analysis of Nsp1β deletion constructs showed that the N-terminal domain of Nsp1β was involved in the ubiquitin-proteasomal degradation of KPNA1. A nucleotide substitution resulting in an amino acid change from valine to isoleucine at residue 19 of Nsp1β diminished its ability to induce KPNA1 degradation and to inhibit IFN-mediated signaling. Interestingly, infection of MARC-145 cells by PRRSV strains VR-2332 and VR-2385 also resulted in KPNA1 reduction, whereas infection by an avirulent strain, Ingelvac PRRS modified live virus (MLV), did not. MLV Nsp1β had no effect on KPNA1; however, a mutant with an amino acid change at residue 19 from isoleucine to valine induced KPNA1 degradation. These results indicate that Nsp1β blocks ISGF3 nuclear translocation by inducing KPNA1 degradation and that valine-19 in Nsp1β correlates with the inhibition.",,"['Wang, Rong', 'Nan, Yuchen', 'Yu, Ying', 'Zhang, Yan-Jin']",,,,
,PMC,The pH of Activation of the Hemagglutinin Protein Regulates H5N1 Influenza Virus Replication and Pathogenesis in Mice,http://dx.doi.org/10.1128/JVI.03110-12,PMC3624295,,,"After receptor binding and internalization during influenza virus entry, the hemagglutinin (HA) protein is triggered by low pH to undergo irreversible conformational changes that mediate membrane fusion. To investigate how mutations that alter the activation pH of the HA protein influence the fitness of an avian H5N1 influenza virus in a mammalian model, we infected C57BL/6J or DBA/2J mice and compared the replication and virulence of recombinant A/chicken/Vietnam/C58/04 (H5N1) HA-Y23(1)H mutant, wild-type, and HA-H24(1)Q and HA-K58(2)I mutant viruses that have HA activation pH values of 6.3, 5.9, 5.6, and 5.4, respectively. The HA-Y23(1)H mutant virus was highly susceptible to acid inactivation in vitro and was attenuated for growth and virulence in mice, suggesting that an H5N1 HA protein triggered at pH 6.3 is too unstable for the virus to remain fit. Wild-type and HA-H24(1)Q viruses were similar in pathogenicity and grew to similar levels in mice, ducks, and cell cultures derived from both avian and mammalian tissues, suggesting that H5N1 HA proteins triggered at pH values in the range of 5.9 to 5.6 broadly support replication. The HA-K58(2)I mutant virus had greater growth and virulence in DBA/2J mice than the wild type did, although the mutant virus was highly attenuated in ducks. The data suggest that adaptation of avian H5N1 influenza virus for infection in mammals is supported by a decrease in the HA activation pH to 5.4. Identification of the HA activation pH as a host-specific infectivity factor is expected to aid in the surveillance and risk assessment of currently circulating H5N1 influenza viruses.",,"['Zaraket, Hassan', 'Bridges, Olga A.', 'Russell, Charles J.']",,,,
,PMC,The Nonstructural Protein 2C of a Picorna-Like Virus Displays Nucleic Acid Helix Destabilizing Activity That Can Be Functionally Separated from Its ATPase Activity,http://dx.doi.org/10.1128/JVI.00245-13,PMC3624285,,,"Picorna-like viruses in the Picornavirales order are a large group of positive-strand RNA viruses that include numerous important pathogens for plants, insects, and humans. In these viruses, nonstructural protein 2C is one of the most conserved proteins and contains ATPase activity and putative RNA helicase activity. Here we expressed 2C protein of Ectropis obliqua picorna-like virus (EoV; genus Iflavirus, family Iflaviridae, order Picornavirales) in a eukaryotic expression system and determined that EoV 2C displays ATP-independent nucleic acid helix destabilizing and strand annealing acceleration activity in a concentration-dependent manner, indicating that this picornaviral 2C is more like an RNA chaperone than like the previously predicted RNA helicase. Our further characterization of EoV 2C revealed that divalent metal ions, such as Mg(2+) and Zn(2+), inhibit 2C-mediated helix destabilization to different extents. Moreover, we determined that EoV 2C also contains ATPase activity like that of other picornaviral 2C proteins and further assessed the functional relevance between its RNA chaperone-like and ATPase activities using mutational analysis as well as their responses to Mg(2+). Our data show that, when one of the two 2C activities was dramatically inhibited or almost abolished, the other activity could remain intact, showing that the RNA chaperone-like and ATPase activities of EoV 2C can be functionally separated. This report reveals that a picorna-like virus 2C protein displays RNA helix destabilizing and strand annealing acceleration activity, which may be critical for picornaviral replication and pathogenesis, and should foster our understanding of picorna-like viruses and viral RNA chaperones.",,"['Cheng, Zhenyun', 'Yang, Jie', 'Xia, Hongjie', 'Qiu, Yang', 'Wang, Zhaowei', 'Han, Yajuan', 'Xia, Xiaoling', 'Qin, Cheng-Feng', 'Hu, Yuanyang', 'Zhou, Xi']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00639-13,PMC3624284,,,,,,,,,
,PMC,Oseltamivir-resistant influenza A(H1N1)pdm09 virus in southern Brazil,http://dx.doi.org/10.1590/S0074-02762013000300021,PMC4005575,,,"The neuraminidase (NA) genes of A(H1N1)pdm09 influenza virus isolates from 306 infected patients were analysed. The circulation of oseltamivir-resistant viruses in Brazil has not been reported previously. Clinical samples were collected in the state of Rio Grande do Sul (RS) from 2009-2011 and two NA inhibitor-resistant mutants were identified, one in 2009 (H275Y) and the other in 2011 (S247N). This study revealed a low prevalence of resistant viruses (0.8%) with no spread of the resistant mutants throughout RS.",,"['Marx, Camila', 'Gregianini, Tatiana Schäffer', 'Lehmann, Fernanda Kieling Moreira', 'Lunge, Vagner Ricardo', 'de Carli, Silvia', 'Dambrós, Bibiana Paula', 'Tumioto, Gabriela Luchiari', 'Seadi, Claudete', 'Fonseca, André Salvador Kazantzi', 'Ikuta, Nilo']",,,,
,PMC,Polymicrobial Acute Respiratory Infections in a Hospital-Based Pediatric Population,http://dx.doi.org/10.1097/INF.0b013e31828683ce,PMC3701747,,,"BACKGROUND: The clinical impact of polymicrobial respiratory infections remains uncertain. Previous reports are contradictory regarding an association with severe disease. METHODS: Three hundred and forty-six specimens from children with acute respiratory illness identified at the University of Iowa Hospitals and Clinics Clinical Microbiology Laboratory (CML) were evaluated by DFA, and/or viral culture by CML and later by molecular study for the presence of influenza, parainfluenza (HPIV), respiratory syncytial virus (HRSV), adenovirus (HAdV), human metapneumovirus (HMPV), rhinovirus (HRV), and human bocavirus (HBoV). Demographic and clinical data were abstracted from medical records. RESULTS: Multiple viruses were detected in 46 (21.7%) of 212 virus-positive specimens with the most frequent virus-virus combinations being HRV-HRSV (n=12), HRV-HBoV (n=6), and HRV-HPIV 3 (n=4). Risk factors for coinfection included: male gender (OR 1.70, 95% CI 0.83–3.46), 6 mos-1 yr age (OR 2.15, 95% CI 0.75–6.19), and history of immunosuppression (OR 2.05, 95% CI 0.99–4.23). Children with viral coinfections were less likely than children with single virus infections to be admitted to an intensive care unit (OR 0.32, 95% CI 1.12–9.17), however, this may be explained by undetected viral-bacterial coinfections. CONCLUSIONS: HRV, HRSV, HBoV and polymicrobial infections were prevalent in this study. While the cross-sectional design could not easily examine polymicrobial infection and disease severity, prospective, population-based research regarding the clinical impact of such infections is warranted.",,"['Chorazy, Margaret L.', 'Lebeck, Mark G.', 'McCarthy, Troy A.', 'Richter, Sandra S.', 'Torner, James C.', 'Gray, Gregory C.']",,,,
,PMC,The Role of the Intestinal Microbiota in the Pathogenesis of Necrotizing Enterocolitis,http://dx.doi.org/10.1053/j.sempedsurg.2013.01.002,PMC3647029,,,"Development of necrotizing enterocolitis (NEC) requires a susceptible host, typically a premature infant or an infant with congenital heart disease, enteral feedings and bacterial colonization. Although there is little doubt that microbes are critically involved in the pathogenesis of NEC, the identity of specific causative pathogens remains elusive. Unlike established normal adult gut microbiota, which is quite complex, uniform, and stable, early postnatal bacterial populations are simple, diverse, and fluid. These properties complicate studies aimed at elucidating characteristics of the gut microbiome that may play a role in the pathogenesis of NEC. A broad variety of bacterial, viral, and fungal species have been implicated in both clinical and experimental NEC. Frequently, however, the same species have also been found in physiologically matched healthy individuals. Clustered outbreaks of NEC, in which the same strain of a suspected pathogen is detected in several patients suggest, but do not prove, a causative relationship between the specific pathogen and the disease. Studies in Cronobacter sakazakii, the best characterized NEC pathogen, have demonstrated that virulence is not a property of a bacterial species as a whole, but rather a characteristic of certain strains, which may explain why the same species can be pathogenic or non-pathogenic. The fact that a given microbe may be innocuous in a full-term, yet pathogenic in a pre-term infant has led to the idea of opportunistic pathogens in NEC. Progress in understanding the infectious nature of NEC may require identifying specific pathogenic strains and unambiguously establishing their virulence in animal models.",,"['Grishin, Anatoly', 'Papillon, Stephanie', 'Bell, Brandon', 'Wang, Jin', 'Ford, Henri R.']",,,,
,PMC,Influenza vaccination in children at high risk of respiratory disease,http://dx.doi.org/10.1177/2051013613480770,PMC3967668,,,"Chronic respiratory diseases (CRDs) are a heterogeneous group of diseases that can affect the pediatric population and health authorities throughout the world recommend influenza vaccination because of the significant risk of influenza-related complications. However, despite this recommendation, vaccine coverage is generally unsatisfactory. The aim of this review is to analyze the impact of influenza on children at high risk of respiratory disease, and the immunogenicity, safety and efficacy of influenza vaccination in such children. The results show that there is a significant risk of influenza-related complications in preterm neonates and infants, in whom influenza vaccines are immunogenic and safe (although their efficacy has not been specifically studied). There are conflicting data concerning the effect of influenza infection on asthma morbidity in children, and whether or not influenza vaccination helps to prevent asthma exacerbations. Recent data provide no evidence that influenza is more frequent in patients with cystic fibrosis than in healthy subjects, or that it is responsible for increased lower respiratory tract morbidity. The lack of any clear correlate of protection suggests that future studies should also consider the efficacy of the different influenza vaccines and not only evaluate them in terms of immunogenicity. Furthermore, there is a need for clinical studies to assess the effectiveness of the available vaccines in patients with other rare CRDs and other chronic underlying diseases with possibly severe respiratory involvement. It is also important to determine whether children with recurrent respiratory tract infections should be included in the list of those for whom influenza vaccination is recommended. In the meantime, given the increasing evidence of the burden of influenza on the population as a whole and the benefits associated with vaccination, annual influenza vaccinations should be recommended for all children at high risk of respiratory disease and the members of their households.",,"['Patria, Maria Francesca', 'Tagliabue, Claudia', 'Longhi, Benedetta', 'Esposito, Susanna']",,,,
,PMC,"Widespread but tissue-specific patterns of interferon-induced transmembrane protein 3 (IFITM3, FRAGILIS, MIL-1) in the mouse gastrula",http://dx.doi.org/10.1016/j.gep.2013.04.003,PMC3704145,,,"Interferon-induced transmembrane protein 3 (IFITM3; FRAGILIS; MIL-1) is part of a larger family of important small interferon-induced transmembrane genes and proteins involved in early development, cell adhesion, and cell proliferation, and which also play a major role in response to bacterial and viral infections and, more recently, in pronounced malignancies (Siegrist et al., 2011). IFITM3, together with tissue-nonspecific alkaline phosphatase (TNAP), PRDM1, and STELLA, has been claimed to be a hallmark of segregated primordial germ cells (PGCs) (Saitou et al., 2002). However, whether IFITM3, like STELLA, is part of a broader stem/progenitor pool that builds the posterior region of the mouse conceptus (Mikedis and Downs, 2012), is obscure. To discover the whereabouts of IFITM3 during mouse gastrulation (~E6.5-9.0), systematic immunohistochemical analysis was carried out at closely spaced 2-4-hour intervals. Results revealed diverse, yet consistent, profiles of IFITM3 localization throughout the gastrula. Within the putative PGC trajectory and surrounding posterior tissues, IFITM3 localized as a large cytoplasmic spot with or without staining in the plasma membrane. IFITM3, like STELLA, was also found in the ventral ectodermal ridge (VER), a posterior progenitor pool that builds the tailbud. The large cytoplasmic spot with plasma membrane staining was exclusive to the posterior region; the visceral yolk sac, non-posterior tissues, and epithelial tissues exhibited spots of IFITM3 without cell surface staining. Co-localization of the intracellular IFITM3 spot with the endoplasmic reticulum, Golgi apparatus or endolysosomes was not observed. That relatively high levels of IFITM3 were found throughout the posterior primitive streak and its derivatives is consistent with evidence that IFITM3, like STELLA, is part of a larger stem/progenitor cell pool at the posterior end of the primitive streak that forms the base of the allantois and builds the fetal-umbilical connection, thus further obfuscating practical phenotypic distinctions between so-called PGCs and surrounding soma.",,"['Mikedis, Maria M.', 'Downs, Karen M.']",,,,
,PMC,Differentiated phenotypes of primary murine alveolar epithelial cells and their susceptibility to infection by respiratory viruses,http://dx.doi.org/10.1016/j.virusres.2013.04.008,PMC3683362,,,"Severe respiratory viral infections are associated with spread to the alveoli of the lungs. There are multiple murine models of severe respiratory viral infections that have been used to identify viral and host factors that contribute to disease severity. Primary cultures of murine alveolar epithelial cells provide a robust in vitro model to perform mechanistic studies that can be correlated with in vivo studies to identify cell type-specific factors that contribute to pathology within the alveoli of the lung during viral infection. In this study, we established an in vitro model to compare the responses of type I (ATI) and type II (ATII) alveolar epithelial cells to infection by respiratory viruses used in murine models: mouse-adapted severe acute respiratory syndrome-associated coronavirus (SARS-CoV, v2163), murine coronavirus MHV-1, and influenza A (H1N1) virus, strain PR8. Murine alveolar cells cultured to maintain an ATII cell phenotype, determined by expression of LBP180, were susceptible to infection by all three viruses. In contrast, ATII cells that were cultured to trans-differentiate into an ATI-like cell phenotype were susceptible to MHV-1 and PR8, but not mouse-adapted SARS-CoV. Epithelial cells produce cytokines in response to viral infections, thereby activating immune responses. Thus, virus-induced cytokine expression was quantified in ATI and ATII cells. Both cell types had increased expression of IL-1β mRNA upon viral infection, though at different levels. While MHV-1 and PR8 induced expression of a number of shared cytokines in ATI cells, there were several cytokines whose expression was induced uniquely by MHV-1 infection. In summary, ATI and ATII cells exhibited differential susceptibilities and cytokine responses to infection by respiratory viruses. This in vitro model will be critical for future studies to determine the roles of these specialized cell types in the pathogenesis of respiratory viral infection.",,"['Kebaabetswe, Lemme P.', 'Haick, Anoria K.', 'Miura, Tanya A.']",,,,
,PMC,"The Serial Intervals of Seasonal and Pandemic Influenza Viruses in Households in Bangkok, Thailand",http://dx.doi.org/10.1093/aje/kws402,PMC3676150,,,"The serial interval (SI) of human influenza virus infections is often described by a single distribution. Understanding sources of variation in the SI could provide valuable information for understanding influenza transmission dynamics. Using data from a randomized household study of nonpharmaceutical interventions to prevent influenza transmission in Bangkok, Thailand, over 34 months between 2008 and 2011, we estimated the influence of influenza virus type/subtype and other characteristics of 251 pediatric index cases and their 315 infected household contacts on estimates of household SI. The mean SI for all households was 3.3 days. Relative to influenza A(H1N1)pdm09 (3.1 days), the SI for influenza B (3.7 days) was 22% longer (95% confidence interval: 4, 43), or about half a day. The SIs for influenza viruses A(H1N1) and A(H3N2) were similar to that for A(H1N1)pdm09. SIs were shortest for older index cases (age 11–14 years) and for younger infected household contacts (age ≤15 years). Greater time spent in proximity to the index child was associated with shorter SIs. Differences in the SI might reflect differences in incubation period, viral shedding, contact, or susceptibility. These findings could improve parameterization of mathematical models to better predict the impact of epidemic or pandemic influenza mitigation strategies.",,"['Levy, Jens W.', 'Cowling, Benjamin J.', 'Simmerman, James M.', 'Olsen, Sonja J.', 'Fang, Vicky J.', 'Suntarattiwong, Piyarat', 'Jarman, Richard G.', 'Klick, Brendan', 'Chotipitayasunondh, Tawee']",,,,
,PMC,Abstracts from the 36th Annual Meeting of the Society of General Internal Medicine,http://dx.doi.org/10.1007/s11606-013-2436-y,PMC3654146,,,,,,,,,
,PMC,Negatively charged residues in the endodomain are critical for specific assembly of spike protein into murine coronavirus,http://dx.doi.org/10.1016/j.virol.2013.04.001,PMC3772176,,,"Coronavirus spike (S) protein assembles into virions via its carboxy-terminus, which is composed of a transmembrane domain and an endodomain. Here, the carboxy-terminal charge-rich motif in the endodomain was verified to be critical for the specificity of S assembly into mouse hepatitis virus (MHV). Recombinant MHVs exhibited a range of abilities to accommodate the homologous S endodomains from the betacoronaviruses bovine coronavirus and human SARS-associated coronavirus, the alphacoronavirus porcine transmissible gastroenteritis virus (TGEV), and the gammacoronavirus avian infectious bronchitis virus respectively. Interestingly, in TGEV endodomain chimeras the reverting mutations resulted in stronger S incorporation into virions, and a net gain of negatively charged residues in the charge-rich motif accounted for the improvement. Additionally, MHV S assembly could also be rescued by the acidic carboxy-terminal domain of the nucleocapsid protein. These results indicate an important role for negatively charged endodomain residues in the incorporation of MHV S protein into assembled virions.",,"['Yao, Qianqian', 'Masters, Paul S.', 'Ye, Rong']",,,,
,PMC,Efficient delivery of RNA interference oligonucleotides to polarized airway epithelia in vitro,http://dx.doi.org/10.1152/ajplung.00426.2012,PMC4073929,,,"Polarized and pseudostratified primary airway epithelia present barriers that significantly reduce their transfection efficiency and the efficacy of RNA interference oligonucleotides. This creates an impediment in studies of the airway epithelium, diminishing the utility of loss-of-function as a research tool. Here we outline methods to introduce RNAi oligonucleotides into primary human and porcine airway epithelia grown at an air-liquid interface and difficult-to-transfect transformed epithelial cell lines grown on plastic. At the time of plating, we reverse transfect small-interfering RNA (siRNA), Dicer-substrate siRNA, or microRNA oligonucleotides into cells by use of lipid or peptide transfection reagents. Using this approach we achieve significant knockdown in vitro of hypoxanthine-guanine phosphoribosyltransferase, IL-8, and CFTR expression at the mRNA and protein levels in 1–3 days. We also attain significant reduction of secreted IL-8 in polarized primary pig airway epithelia 3 days posttransfection and inhibition of CFTR-mediated Cl(−) conductance in polarized air-liquid interface cultures of human airway epithelia 2 wk posttransfection. These results highlight an efficient means to deliver RNA interference reagents to airway epithelial cells and achieve significant knockdown of target gene expression and function. The ability to reliably conduct loss-of-function assays in polarized primary airway epithelia offers benefits to research in studies of epithelial cell homeostasis, candidate gene function, gene-based therapeutics, microRNA biology, and targeting the replication of respiratory viruses.",,"['Ramachandran, Shyam', 'Krishnamurthy, Sateesh', 'Jacobi, Ashley M.', 'Wohlford-Lenane, Christine', 'Behlke, Mark A.', 'Davidson, Beverly L.', 'McCray, Paul B.']",,,,
,PMC,Abrogation of ER stress-induced apoptosis of alveolar epithelial cells by angiotensin 1–7,http://dx.doi.org/10.1152/ajplung.00001.2013,PMC3726942,,,"Earlier work showed that apoptosis of alveolar epithelial cells (AECs) in response to endogenous or xenobiotic factors is regulated by autocrine generation of angiotensin (ANG) II and its counterregulatory peptide ANG1–7. Mutations in surfactant protein C (SP-C) induce endoplasmic reticulum (ER) stress and apoptosis in AECs and cause lung fibrosis. This study tested the hypothesis that ER stress-induced apoptosis of AECs might also be regulated by the autocrine ANGII/ANG1–7 system of AECs. ER stress was induced in A549 cells or primary cultures of human AECs with the proteasome inhibitor MG132 or the SP-C BRICHOS domain mutant G100S. ER stress activated the ANGII-generating enzyme cathepsin D and simultaneously decreased the ANGII-degrading enzyme ACE-2, which normally generates the antiapoptotic peptide ANG1–7. TAPI-2, an inhibitor of ADAM17/TACE, significantly reduced both the activation of cathepsin D and the loss of ACE-2. Apoptosis of AECs induced by ER stress was measured by assays of mitochondrial function, JNK activation, caspase activation, and nuclear fragmentation. Apoptosis induced by either MG132 or the SP-C BRICHOS mutant G100S was significantly inhibited by the ANG receptor blocker saralasin and was completely abrogated by ANG1–7. Inhibition by ANG1–7 was blocked by the specific mas antagonist A779. These data show that ER stress-induced apoptosis is mediated by the autocrine ANGII/ANG1–7 system in human AECs and demonstrate effective blockade of SP-C mutation-induced apoptosis by ANG1–7. They also suggest that therapeutic strategies aimed at administering ANG1–7 or stimulating ACE-2 may hold potential for the management of ER stress-induced fibrotic lung disorders.",,"['Uhal, Bruce D.', 'Nguyen, Hang', 'Dang, MyTrang', 'Gopallawa, Indiwari', 'Jiang, Jing', 'Dang, Vinh', 'Ono, Shinji', 'Morimoto, Konosuke']",,,,
,PMC,The present and future of solution NMR in investigating the structure and dynamics of channels and transporters,http://dx.doi.org/10.1016/j.sbi.2013.03.010,PMC3740178,,,"Membrane channels, transporters and receptors constitute essential means for cells to maintain homeostasis and communicate with the surroundings. Investigation of their molecular architecture and the dynamic process of transporting substrate or transmitting signals across the membrane barrier has been one of the frontiers in biomedical research. The past decade has seen numerous successes in the use of x-ray or electron crystallography in determining atomic-resolution structures of membrane proteins, and in some cases, even snapshots of different physiological states of the same protein have been obtained. But there are also many cases in which long-standing efforts to crystallize proteins have yet to succeed. Therefore we have practical needs for developing complementary biophysical tools such as NMR spectroscopy and electron microscopy for tackling these systems. This paper provides a number of key examples where the utility of solution NMR was pivotal in providing structural and functional information of ion channels and transporters.",,"['Oxenoid, Kirill', 'Chou, James J.']",,,,
,PMC,Geminivirus protein structure and function,http://dx.doi.org/10.1111/mpp.12032,PMC6638828,,,"Geminiviruses are a family of plant viruses that cause economically important plant diseases worldwide. These viruses have circular single‐stranded DNA genomes and four to eight genes that are expressed from both strands of the double‐stranded DNA replicative intermediate. The transcription of these genes occurs under the control of two bidirectional promoters and one monodirectional promoter. The viral proteins function to facilitate virus replication, virus movement, the assembly of virus‐specific nucleoprotein particles, vector transmission and to counteract plant host defence responses. Recent research findings have provided new insights into the structure and function of these proteins and have identified numerous host interacting partners. Most of the viral proteins have been shown to be multifunctional, participating in multiple events during the infection cycle and have, indeed, evolved coordinated interactions with host proteins to ensure a successful infection. Here, an up‐to‐date review of viral protein structure and function is presented, and some areas requiring further research are identified.",,"Fondong, Vincent N.",,,,
,PMC,A divergent clade of circular single-stranded DNA viruses from pig feces,http://dx.doi.org/10.1007/s00705-013-1701-z,PMC4175981,,,"Using metagenomics and molecular cloning methods, we characterized five novel small, circular viral genomes from pig feces that are distantly related to chimpanzee and porcine stool-associated circular viruses, (ChiSCV and PoSCV1). Phylogenetic analysis placed these viruses into a highly divergent clade of this rapidly growing new viral family. This new clade of viruses, provisionally named porcine stool-associated circular virus 2 and 3 (PoSCV2 and PoSCV3), encodes a stem–loop structure (presumably the origin of DNA replication) in the small intergenic region and a replication initiator protein commonly found in other biological systems that replicate their genomes via the rolling–circle mechanism. Furthermore, these viruses also exhibit three additional overlapping open reading frames in the large intergenic region between the capsid and replication initiator protein genes.",,"['Cheung, Andrew K.', 'Ng, Terry F.', 'Lager, Kelly M.', 'Bayles, Darrell O.', 'Alt, David P.', 'Delwart, Eric L.', 'Pogranichniy, Roman M.', 'Kehrli, Marcus E.']",,,,
,PMC,Cleavage Activation of Human-adapted Influenza Virus Subtypes by Kallikrein-related Peptidases 5 and 12,http://dx.doi.org/10.1074/jbc.M112.440362,PMC3682540,,,"A critical step in the influenza virus replication cycle is the cleavage activation of the HA precursor. Cleavage activation of influenza HA enables fusion with the host endosome, allowing for release of the viral genome into the host cell. To date, studies have determined that HA activation is driven by trypsin-like host cell proteases, as well as yet to be identified bacterial proteases. Although the number of host proteases that can activate HA is growing, there is still uncertainty regarding which secreted proteases are able to support multicycle replication of influenza. In this study, we have determined that the kallikrein-related peptidases 5 and 12 are secreted from the human respiratory tract and have the ability to cleave and activate HA from the H1, H2, and H3 subtypes. Each peptidase appears to have a preference for particular influenza subtypes, with kallikrein 5 cleaving the H1 and H3 subtypes most efficiently and kallikrein 12 cleaving the H1 and H2 subtypes most efficiently. Cleavage analysis using HA cleavage site peptide mimics revealed that the amino acids neighboring the arginine cleavage site affect cleavage efficiency. Additionally, the thrombolytic zymogens plasminogen, urokinase, and plasma kallikrein have all been shown to cleave and activate influenza but are found circulating mainly as inactive precursors. Kallikrein 5 and kallikrein 12 were examined for their ability to activate the thrombolytic zymogens, and both resulted in activation of each zymogen, with kallikrein 12 being a more potent activator. Activation of the thrombolytic zymogens may therefore allow for both direct and indirect activation of the HA of human-adapted influenza viruses by kallikrein 5 and kallikrein 12.",,"['Hamilton, Brian S.', 'Whittaker, Gary R.']",,,,
,PMC,Bats are a major natural reservoir for hepaciviruses and pegiviruses,http://dx.doi.org/10.1073/pnas.1303037110,PMC3657805,,,"Although there are over 1,150 bat species worldwide, the diversity of viruses harbored by bats has only recently come into focus as a result of expanded wildlife surveillance. Such surveys are of importance in determining the potential for novel viruses to emerge in humans, and for optimal management of bats and their habitats. To enhance our knowledge of the viral diversity present in bats, we initially surveyed 415 sera from African and Central American bats. Unbiased high-throughput sequencing revealed the presence of a highly diverse group of bat-derived viruses related to hepaciviruses and pegiviruses within the family Flaviridae. Subsequent PCR screening of 1,258 bat specimens collected worldwide indicated the presence of these viruses also in North America and Asia. A total of 83 bat-derived viruses were identified, representing an infection rate of nearly 5%. Evolutionary analyses revealed that all known hepaciviruses and pegiviruses, including those previously documented in humans and other primates, fall within the phylogenetic diversity of the bat-derived viruses described here. The prevalence, unprecedented viral biodiversity, phylogenetic divergence, and worldwide distribution of the bat-derived viruses suggest that bats are a major and ancient natural reservoir for both hepaciviruses and pegiviruses and provide insights into the evolutionary history of hepatitis C virus and the human GB viruses.",,"['Quan, Phenix-Lan', 'Firth, Cadhla', 'Conte, Juliette M.', 'Williams, Simon H.', 'Zambrana-Torrelio, Carlos M.', 'Anthony, Simon J.', 'Ellison, James A.', 'Gilbert, Amy T.', 'Kuzmin, Ivan V.', 'Niezgoda, Michael', 'Osinubi, Modupe O. V.', 'Recuenco, Sergio', 'Markotter, Wanda', 'Breiman, Robert F.', 'Kalemba, Lems', 'Malekani, Jean', 'Lindblade, Kim A.', 'Rostal, Melinda K.', 'Ojeda-Flores, Rafael', 'Suzan, Gerardo', 'Davis, Lora B.', 'Blau, Dianna M.', 'Ogunkoya, Albert B.', 'Alvarez Castillo, Danilo A.', 'Moran, David', 'Ngam, Sali', 'Akaibe, Dudu', 'Agwanda, Bernard', 'Briese, Thomas', 'Epstein, Jonathan H.', 'Daszak, Peter', 'Rupprecht, Charles E.', 'Holmes, Edward C.', 'Lipkin, W. Ian']",,,,
,PMC,Genetic Susceptibility to Feline Infectious Peritonitis in Birman Cats,http://dx.doi.org/10.1016/j.virusres.2013.04.006,PMC4342855,,,"Genetic factors are presumed to influence the incidence of feline infectious peritonitis (FIP), especially among pedigreed cats. However, proof for the existence of such factors has been limited and mainly anecdotal. Therefore, we sought evidence for genetic susceptibility to FIP using feline high density single nucleotide polymorphism (SNP) arrays in a genome-wide association study (GWAS). Birman cats were chosen for GWAS because they are highly inbred and suffer a high incidence of FIP. DNA from 38 Birman cats that died of FIP and 161 healthy cats from breeders in Denmark and USA were selected for genotyping using 63K SNPs distributed across the feline genome. Danish and American Birman cats were closely related and the populations were therefore combined and analyzed in two manners: 1) all cases (FIP) vs. all controls (healthy) regardless of age, and 2) cases 1–1/2 years of age and younger (most susceptible) vs. controls 2 years of age and older (most resistant). GWAS of the second cohort was most productive in identifying significant genome-wide associations between case and control cats. Four peaks of association with FIP susceptibility were identified, with two being identified on both analyses. Five candidate genes ELMO1, RRAGA, TNFSF10, ERAP1 and ERAP2, all relevant to what is known about FIP virus pathogenesis, were identified but no single association was fully concordant with the disease phenotype. Difficulties in doing GWAS in cats and interrogating complex genetic traits were discussed.",,"['Golovko, Lyudmila', 'Lyons, Leslie A.', 'Liu, Hongwei', 'Sorensen, Anne', 'Wehnert, Suzanne', 'Pedersen, Niels C.']",,,,
,PMC,H5N1 receptor specificity as a factor in pandemic risk,http://dx.doi.org/10.1016/j.virusres.2013.02.015,PMC3805702,,,"The high pathogenicity of H5N1 viruses in sporadic infections of humans has raised concerns for its potential to acquire the ability to transmit between humans and emerge as a highly pathogenic pandemic virus. Because avian and human influenza viruses differ in their specificity for recognition of their host cell receptors, receptor specificity represents one barrier for efficient transmission of avian viruses in human hosts. Over the last century, each influenza virus pandemic has coincided with the emergence of virus with an immunologically distinct hemagglutinin exhibiting a ‘human-type’ receptor specificity, distinct from that of viruses with the same hemagglutinin circulating in zoonotic species. Recent studies suggest that it is possible for H5N1 to acquire human type receptor specificity, but this has not occurred in nature. This review covers what is known about the molecular basis for the switch between avian and human-type receptor specificity for influenza viruses that have successfully adapted to man, the potential for H5N1 to evolve to human-type receptor specificity and its relevance to pandemic risk.",,"['Paulson, James C.', 'de Vries, Robert P.']",,,,
,PMC,A high-throughput screen of the GTPase activity of Escherichia coli EngA to find an inhibitor of bacterial ribosome biogenesis,http://dx.doi.org/10.1177/1087057113486001,PMC4061131,,,"The synthesis of ribosomes is an essential process, which is aided by a variety of transacting factors in bacteria. Among these is a group of GTPases essential for bacterial viability and emerging as promising targets for new antibacterial agents. Herein, we describe a robust high-throughput screening process for inhibitors of one such GTPase, the Escherichia coli EngA protein. The primary screen employed an assay of phosphate production in 384-well density. Reaction conditions were chosen to maximize sensitivity for the discovery of competitive inhibitors while maintaining a strong signal amplitude and low noise. In a pilot screen of 31,800 chemical compounds, 44 active compounds were identified. Further, we describe the elimination of non-specific inhibitors that were detergent-sensitive or reactive as well as those that interfered with the high-throughput phosphate assay. Four inhibitors survived these common counter-screens for non-specificity but these chemicals were also inhibitors of the unrelated enzyme dihydrofolate reductase, suggesting that they too were promiscuously active. The high-throughput screen of the EngA protein described here provides a meticulous pilot study in the search for specific inhibitors of GTPases involved in ribosome biogenesis.",,"['Bharat, Amrita', 'Blanchard, Jan E.', 'Brown, Eric D.']",,,,
,PMC,Viral Precursor Polyproteins: Keys of Regulation from Replication to Maturation,http://dx.doi.org/10.1016/j.coviro.2013.03.009,PMC3660988,,,"Many viruses use a replication strategy involving the translation of a large polyprotein, which is cleaved by viral and/or cellular proteases. Several of these viruses severely impact human health around the globe, including HIV, HCV, Dengue virus, and West Nile virus. This method of genome organization has many benefits to the virus such as condensation of genetic material, as well as temporal and spatial regulation of protein activity depending on polyprotein cleavage state. The study of polyprotein precursors is necessary to fully understand viral infection, and identify possible new drug targets; however, few atomic structures are currently available. Presented here are structures of four recent polyprotein precursors from viruses with a positive sense RNA genome.",,"['Yost, Samantha A.', 'Marcotrigiano, Joseph']",,,,
,PMC,Understanding immune senescence to improve vaccine responses,http://dx.doi.org/10.1038/ni.2588,PMC4183346,,,"In the older adult the benefits of vaccination to prevent infectious disease are limited, mainly due to the adaptive immune system’s inability to generate protective immunity. Age-dependent decline in immune competence, often referred to as immunosenescence, results from progressive deterioration of innate and adaptive immune responses and most of the insights into mechanisms of immune aging have derived from studies in murine models. In this Review, we explore how well these models are applicable to understand the aging process throughout the 80–100 years of human life and discuss recent advances in uncovering and characterizing the mechanisms underlying age-associated defective adaptive immunity in humans.",,"['Goronzy, Jörg J.', 'Weyand, Cornelia M.']",,,,
,PMC,The antiviral effector IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry,http://dx.doi.org/10.1016/j.chom.2013.03.006,PMC3646482,,,"Vesicle-membrane-protein-associated protein A (VAPA) and oxysterol-binding protein (OSBP) regulate intracellular cholesterol homeostasis, which is required for many virus infections. During entry, viruses or virus-containing vesicles can fuse with endosomal membranes to mediate the cytosolic release of virions, and alterations in endosomal cholesterol can inhibit this invasion step. We show that the antiviral effector protein Interferon-inducible transmembrane protein 3 (IFITM3) interacts with VAPA and prevents its association with OSBP, thereby disrupting intracellular cholesterol homeostasis and inhibiting viral entry. By altering VAPA-OSBP function, IFITM3 induces a marked accumulation of cholesterol in multivesicular bodies and late endosomes, which inhibits the fusion of intraluminal virion-containing vesicles with endosomal membranes and thereby blocks virus release into the cytosol. Consequently, ectopic expression or depletion of the VAPA gene profoundly affects IFITM3-mediated inhibition of viral entry. Thus, IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry, further underscoring the importance of cholesterol in virus infection.",,"['Amini-Bavil-Olyaee, Samad', 'Choi, Youn Jung', 'Lee, Jun Han', 'Shi, Mude', 'Huang, I-Chueh', 'Farzan, Michael', 'Jung, Jae U.']",,,,
,PMC,Viral surveillance and discovery,http://dx.doi.org/10.1016/j.coviro.2013.03.010,PMC4310698,,,"The field of virus discovery has burgeoned with the advent of high throughput sequencing platforms and bioinformatics programs that enable rapid identification and molecular characterization of known and novel agents, investments in global microbial surveillance that include wildlife and domestic animals as well as humans, and recognition that viruses may be implicated in chronic as well as acute diseases. Here we review methods for viral surveillance and discovery, strategies and pitfalls in linking discoveries to disease, and identify opportunities for improvements in sequencing instrumentation and analysis, the use of social media and medical informatics that will further advance clinical medicine and public health.",,"['Lipkin, Walter Ian', 'Firth, Cadhla']",,,,
,PMC,Putative conformations of the receptor-binding domain in S protein of hCoV-EMC in complex with its receptor dipeptidyl peptidase-4,http://dx.doi.org/10.1016/j.jinf.2013.04.007,PMC4355062,,,,,"['Jiang, Shibo', 'Lu, Lu', 'Du, Lanying', 'Debnath, Asim K.']",,,,
,PMC,Interventions to Mitigate Emergency Department and Hospital Crowding During an Infectious Respiratory Disease Outbreak: Results from an Expert Panel,http://dx.doi.org/10.1371/currents.dis.1f277e0d2bf80f4b2bb1dd5f63a13993,PMC3644286,23856917,CC BY,"Objective: To identify and prioritize potential Emergency Department (ED) and hospital-based interventions which could mitigate the impact of crowding during patient surge from a widespread infectious respiratory disease outbreak and determine potential data sources that may be useful for triggering decisions to implement these high priority interventions. Design: Expert panel utilizing Nominal Group Technique to identify and prioritize interventions, and in addition, determine appropriate “triggers” for implementation of the high priority interventions in the context of four different infectious respiratory disease scenarios that vary by patient volumes (high versus low) and illness severity (high versus low). Setting: One day in-person conference held November, 2011. Participants: Regional and national experts representing the fields of public health, disease surveillance, clinical medicine, ED operations, and hospital operations. Main Outcome Measure: Prioritized list of potential interventions to reduce ED and hospital crowding, respectively. In addition, we created a prioritized list of potential data sources which could be useful to trigger interventions. Results: High priority interventions to mitigate ED surge included standardizing admission and discharge criteria and instituting infection control measures. To mitigate hospital crowding, panelists prioritized mandatory vaccination and an algorithm for antiviral use. Data sources identified for triggering implementation of these interventions were most commonly ED and hospital utilization metrics. Conclusions: We developed a prioritized list of potentially useful interventions to mitigate ED and hospital crowding in various outbreak scenarios. The data sources identified to “trigger” the implementation of these high priority interventions consist mainly of sources available at the local, institutional level.",2013 Apr 17,"['Dugas, Andrea Freyer', 'Morton, Melinda', 'Beard, Raphaelle', 'Pines, Jesse M.', 'Bayram, Jamil D.', 'Hsieh, Yu-Hsiang', 'Kelen, Gabor', 'Uscher-Pines, Lori', 'Jeng, Kevin', 'Cole, Gai', 'Rothman, Richard']",PLoS Curr,,,
,PMC,In vitro and In vivo Antitumor Activity of a Novel Alkylating Agent Melphalan-flufenamide Against Multiple Myeloma Cells,http://dx.doi.org/10.1158/1078-0432.CCR-12-3752,PMC4098702,,,"PURPOSE: The alkylating agent melphalan prolongs survival in multiple myeloma (MM) patients; however, it is associated with toxicities and development of drug-resistance. Here, we evaluated the efficacy of melphalan-flufenamide (Mel-flufen), a novel dipeptide prodrug of melphalan in MM. EXPERIMENTAL DESIGN: MM cell lines, primary patient cells, and the human MM xenograft animal model were utilized to study the antitumor activity of mel-flufen. RESULTS: Low doses of mel-flufen triggers a more rapid and higher intracellular concentrations of melphalan in MM cells than is achievable by free melphalan. Cytotoxicity analysis showed significantly lower IC(50) of mel-flufen than melphalan in MM cells. Importantly, mel-flufen induces apoptosis even in melphalan-, and bortezomib-resistant MM cells. Mechanistic studies show that siRNA knockdown of aminopeptidase N, a key enzyme mediating intracellular conversion of mel-flufen to melphalan, attenuates anti-MM activity of mel-flufen. Furthermore, mel-flufen-induced apoptosis was associated with: 1) activation of caspases and PARP cleavage; 2) ROS generation; 3) mitochondrial dysfunction and release of cytochrome-c; and 4) induction of DNA damage. Moreover, mel-flufen inhibits MM cell migration and tumor-associated angiogenesis. Human MM xenograft studies showed a more potent inhibition of tumor growth in mice treated with mel-flufen than mice receiving equimolar doses of melphalan. Finally, combining mel-flufen with lenalidomide, bortezomib, or dexamethasone triggers synergistic anti-MM activity. CONCLUSION: Our preclinical study supports clinical evaluation of mel-flufen to enhance therapeutic potential of melphalan, overcome drug-resistance, and improve MM patient outcome.",,"['Chauhan, Dharminder', 'Ray, Arghya', 'Viktorsson, Kristina', 'Spira, Jack', 'Paba-Prada, Claudia', 'Munshi, Nikhil', 'Richardson, Paul', 'Lewensohn, Rolf', 'Anderson, Kenneth C.']",,,,
,PMC,Mapping the crossroads of immune activation and cellular stress response pathways,http://dx.doi.org/10.1038/emboj.2013.80,PMC3642686,,,"The innate immune cell network detects specific microbes and damages to cell integrity in order to coordinate and polarize the immune response against invading pathogens. In recent years, a cross-talk between microbial-sensing pathways and endoplasmic reticulum (ER) homeostasis has been discovered and have attracted the attention of many researchers from the inflammation field. Abnormal accumulation of proteins in the ER can be seen as a sign of cellular malfunction and triggers a collection of conserved emergency rescue pathways. These signalling cascades, which increase ER homeostasis and favour cell survival, are collectively known as the unfolded protein response (UPR). The induction or activation by microbial stimuli of several molecules linked to the ER stress response pathway have led to the conclusion that microbe sensing by immunocytes is generally associated with an UPR, which serves as a signal amplification cascade favouring inflammatory cytokines production. Induction of the UPR alone was shown to promote inflammation in different cellular and pathological models. Here we discuss how the innate immune and ER-signalling pathways intersect. Moreover, we propose that the induction of UPR-related molecules by microbial products does not necessarily reflect ER stress, but instead is an integral part of a specific transcription programme controlled by innate immunity receptors.",,"['Cláudio, Nuno', 'Dalet, Alexandre', 'Gatti, Evelina', 'Pierre, Philippe']",,,,
,PMC,Bioanalysis of eukaryotic organelles,http://dx.doi.org/10.1021/cr300354g,PMC3676536,,,,,"['Satori, Chad P.', 'Henderson, Michelle M.', 'Krautkramer, Elyse A.', 'Kostal, Vratislav', 'Distefano, Mark M.', 'Arriaga, Edgar A.']",,,,
,PMC,A fully synthetic human Fab antibody library based on fixed VH/VL framework pairings with favorable biophysical properties,http://dx.doi.org/10.4161/mabs.24218,PMC4169037,,,"This report describes the design, generation and testing of Ylanthia, a fully synthetic human Fab antibody library with 1.3E+11 clones. Ylanthia comprises 36 fixed immunoglobulin (Ig) variable heavy (VH)/variable light (VL) chain pairs, which cover a broad range of canonical complementarity-determining region (CDR) structures. The variable Ig heavy and Ig light (VH/VL) chain pairs were selected for biophysical characteristics favorable to manufacturing and development. The selection process included multiple parameters, e.g., assessment of protein expression yield, thermal stability and aggregation propensity in fragment antigen binding (Fab) and IgG1 formats, and relative Fab display rate on phage. The framework regions are fixed and the diversified CDRs were designed based on a systematic analysis of a large set of rearranged human antibody sequences. Care was taken to minimize the occurrence of potential posttranslational modification sites within the CDRs. Phage selection was performed against various antigens and unique antibodies with excellent biophysical properties were isolated. Our results confirm that quality can be built into an antibody library by prudent selection of unmodified, fully human VH/VL pairs as scaffolds.",,"['Tiller, Thomas', 'Schuster, Ingrid', 'Deppe, Dorothée', 'Siegers, Katja', 'Strohner, Ralf', 'Herrmann, Tanja', 'Berenguer, Marion', 'Poujol, Dominique', 'Stehle, Jennifer', 'Stark, Yvonne', 'Heßling, Martin', 'Daubert, Daniela', 'Felderer, Karin', 'Kaden, Stefan', 'Kölln, Johanna', 'Enzelberger, Markus', 'Urlinger, Stefanie']",,,,
,PMC,Curing a viral infection by targeting the host: The example of cyclophilin inhibitors,http://dx.doi.org/10.1016/j.antiviral.2013.03.020,PMC4332838,,,"Every step of the viral life cycle is dependent on the host, which potentially can be explored for antiviral targets. Historically, however, drug discovery has focused mainly on viral targets, because of their perceived specificity. Efforts to pursue host targets have been largely hampered by concern over potential on-target toxicity, the lack of predictive cell culture and animal models, and the complexity of host–virus interactions. On the other hand, there are distinct advantages of targeting the host, such as creating a high barrier to resistance, providing broad coverage of different genotypes/serotypes and possibly even multiple viruses, and expanding the list of potential targets, when druggable viral targets are limited. Taking hepatitis C virus (HCV) as the example, there are more than 20 inhibitors of the viral protease, polymerase and NS5A protein currently in advanced clinical testing. However, resistance has become a main challenge with these direct-acting antivirals, because HCV, an RNA virus, is notoriously prone to mutation, and a single mutation in the viral target may prevent the binding of an inhibitor, and rendering it ineffective. Host cyclophilin inhibitors have shown promising effects both in vitro and in patients to prevent the emergence of resistance and to cure HCV infection, either alone or in combination with other agents. They are also capable of blocking the replication of a number of other viral pathogens. While the road to developing host-targeting antivirals has been less traveled, and significant challenges remain, delivering the most effective antiviral regimen, which may comprise inhibitors of both host and viral targets, should be well worth the effort.",,"['Lin, Kai', 'Gallay, Philippe']",,,,
,PMC,A comparison of bats and rodents as reservoirs of zoonotic viruses: are bats special?,http://dx.doi.org/10.1098/rspb.2012.2753,PMC3574368,,,"Bats are the natural reservoirs of a number of high-impact viral zoonoses. We present a quantitative analysis to address the hypothesis that bats are unique in their propensity to host zoonotic viruses based on a comparison with rodents, another important host order. We found that bats indeed host more zoonotic viruses per species than rodents, and we identified life-history and ecological factors that promote zoonotic viral richness. More zoonotic viruses are hosted by species whose distributions overlap with a greater number of other species in the same taxonomic order (sympatry). Specifically in bats, there was evidence for increased zoonotic viral richness in species with smaller litters (one young), greater longevity and more litters per year. Furthermore, our results point to a new hypothesis to explain in part why bats host more zoonotic viruses per species: the stronger effect of sympatry in bats and more viruses shared between bat species suggests that interspecific transmission is more prevalent among bats than among rodents. Although bats host more zoonotic viruses per species, the total number of zoonotic viruses identified in bats (61) was lower than in rodents (68), a result of there being approximately twice the number of rodent species as bat species. Therefore, rodents should still be a serious concern as reservoirs of emerging viruses. These findings shed light on disease emergence and perpetuation mechanisms and may help lead to a predictive framework for identifying future emerging infectious virus reservoirs.",,"['Luis, Angela D.', 'Hayman, David T. S.', ""O'Shea, Thomas J."", 'Cryan, Paul M.', 'Gilbert, Amy T.', 'Pulliam, Juliet R. C.', 'Mills, James N.', 'Timonin, Mary E.', 'Willis, Craig K. R.', 'Cunningham, Andrew A.', 'Fooks, Anthony R.', 'Rupprecht, Charles E.', 'Wood, James L. N.', 'Webb, Colleen T.']",,,,
,PMC,Infectious disease transmission as a forensic problem: who infected whom?,http://dx.doi.org/10.1098/rsif.2012.0955,PMC3627102,,,"Observations on infectious diseases often consist of a sample of cases, distinguished by symptoms, and other characteristics, such as onset dates, spatial locations, genetic sequence of the pathogen and/or physiological and clinical data. Cases are often clustered, in space and time, suggesting that they are connected. By defining kernel functions for pairwise analysis of cases, a matrix of transmission probabilities can be estimated. We set up a Bayesian framework to integrate various sources of information to estimate the transmission network. The method is illustrated by analysing data from a multi-year study (2002–2007) of nosocomial outbreaks of norovirus in a large university hospital in the Netherlands. The study included 264 cases, the norovirus genotype was known in approximately 60 per cent of the patients. Combining all the available data allowed likely identification of individual transmission links between most of the cases (72%). This illustrates that the proposed method can be used to accurately reconstruct transmission networks, enhancing our understanding of outbreak dynamics and possibly leading to new insights into how to prevent outbreaks.",,"['Teunis, Peter', 'Heijne, Janneke C. M.', 'Sukhrie, Faizel', 'van Eijkeren, Jan', 'Koopmans, Marion', 'Kretzschmar, Mirjam']",,,,
,PMC,The Lab Without Walls: A Deployable Approach to Tropical Infectious Diseases,http://dx.doi.org/10.4269/ajtmh.12-0704,PMC3617842,,,"The Laboratory Without Walls is a modular field application of molecular biology that provides clinical laboratory support in resource-limited, remote locations. The current repertoire arose from early attempts to deliver clinical pathology and public health investigative services in remote parts of tropical Australia, to address the shortcomings of conventional methods when faced with emerging infectious diseases. Advances in equipment platforms and reagent chemistry have enabling rapid progress, but also ensure the Laboratory Without Walls is subject to continual improvement. Although new molecular biology methods may lead to more easily deployable clinical laboratory capability, logistic and technical governance issues continue to act as important constraints on wider implementation.",,"Inglis, Timothy J. J.",,,,
,PMC,Pneumonia from Human Coronavirus in a Macaque Model,http://dx.doi.org/10.1056/NEJMc1215691,PMC3815470,,,,,"['Munster, Vincent J.', 'de Wit, Emmie', 'Feldmann, Heinz']",,,,
,PMC,The newly emerged SARS-Like coronavirus HCoV-EMC also has an “Achilles’ heel”: current effective inhibitor targeting a 3C-like protease,http://dx.doi.org/10.1007/s13238-013-2841-3,PMC4875521,,,,,"['Ren, Zhilin', 'Yan, Liming', 'Zhang, Ning', 'Guo, Yu', 'Yang, Cheng', 'Lou, Zhiyong', 'Rao, Zihe']",,,,
,PMC,Regulation of Stress Granules and P-Bodies During RNA Virus Infection,http://dx.doi.org/10.1002/wrna.1162,PMC3652661,,,"RNA granules are structures within cells that play major roles in gene expression and homeostasis. Two principle kinds of RNA granules are conserved from yeast to mammals: stress granules (SGs), which contain stalled translation initiation complexes, and processing bodies (P-bodies, PBs), which are enriched with factors involved in RNA turnover. Since RNA granules are associated with silenced transcripts, viruses subvert RNA granule function for replicative advantages. This review, focusing on RNA viruses, discusses mechanisms that manipulate stress granules and P-bodies to promote synthesis of viral proteins. Three main themes have emerged for how viruses manipulate RNA granules; i) cleavage of key host factors, ii) control of PKR activation and iii) redirecting RNA granule components for new or parallel roles in viral reproduction, at the same time disrupting RNA granules. Viruses utilize one or more of these routes to achieve robust and productive infection.",,"Lloyd, Richard E.",,,,
,PMC,Quantum Dot Nanometal Surface Energy Transfer Based Biosensing of Sialic Acid Compositions and Linkages in Biological Samples,http://dx.doi.org/10.1021/ac400320n,PMC5996995,,,"Current methods for analyzing sialic acid diversity in modifications and linkages require multistep processing, derivatization, and chromatographic analyses. We here report a single-step optical method for identification and quantification of different compositions of sialoglycans on glycoproteins and in serum. This was achieved by measuring and quantifying nanometal surface energy transfer (NSET) signals between quantum dots and gold nanoparticles bound to specific sialic acid binding proteins (SBPs) and sialic acid moieties, respectively. The biosensing process is based on the NSET turn-on by external sialic acid species that compete for binding to the SBPs. Selectivity of the biosensor toward sialoglycans can be designed to detect the total amount, glycosylation linkages (α2–6 vs α2–3), and modifications (9-O-acetyl and N-glycolyl groups) in the samples. This nanobiosensor is a prototype expected to achieve limits of the detection down to the micromolar range for high-throughput quantification and analysis of different compositions of sialoglycans present in biological or biomedical samples.",,"['Kikkeri, Raghavendra', 'Padler-Karavani, Vered', 'Diaz, Sandra', 'Verhagen, Andrea', 'Yu, Hai', 'Cao, Hongzhi', 'Langereis, Martijn A.', 'De Groot, Raoul J.', 'Chen, Xi', 'Varki, Ajit']",,,,
,PMC,A decade and a half of protein intrinsic disorder: Biology still waits for physics,http://dx.doi.org/10.1002/pro.2261,PMC3690711,,,"The abundant existence of proteins and regions that possess specific functions without being uniquely folded into unique 3D structures has become accepted by a significant number of protein scientists. Sequences of these intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) are characterized by a number of specific features, such as low overall hydrophobicity and high net charge which makes these proteins predictable. IDPs/IDPRs possess large hydrodynamic volumes, low contents of ordered secondary structure, and are characterized by high structural heterogeneity. They are very flexible, but some may undergo disorder to order transitions in the presence of natural ligands. The degree of these structural rearrangements varies over a very wide range. IDPs/IDPRs are tightly controlled under the normal conditions and have numerous specific functions that complement functions of ordered proteins and domains. When lacking proper control, they have multiple roles in pathogenesis of various human diseases. Gaining structural and functional information about these proteins is a challenge, since they do not typically “freeze” while their “pictures are taken.” However, despite or perhaps because of the experimental challenges, these fuzzy objects with fuzzy structures and fuzzy functions are among the most interesting targets for modern protein research. This review briefly summarizes some of the recent advances in this exciting field and considers some of the basic lessons learned from the analysis of physics, chemistry, and biology of IDPs.",,"Uversky, Vladimir N",,,,
,PMC,"Trajectories of Psychological Distress Among Low-Income, Female Survivors of Hurricane Katrina",http://dx.doi.org/10.1111/ajop.12019,PMC3999519,,,"The purpose of this study was to investigate trajectories of psychological distress among low-income, primarily unmarried and African American women who survived Hurricane Katrina (N = 386). Data were collected in the year prior to the hurricane as well as approximately 1 and 3 years thereafter. Using Latent Class Growth Analysis (LCGA), we detected 6 distinct trajectory groups. Over half of the participants fit into a trajectory consistent with resilience; that is, they maintained low levels of psychological distress over the course of the study, but experienced an elevation in symptoms at the first predisaster time point followed by a return to predisaster levels. The other trajectories reflected a range of psychological responses to disasters and indicated that predisaster functioning had a major influence on postdisaster psychological outcomes. Degree of exposure to hurricane-related stressors, experiences of human and pet bereavement, perceived social support, and socioeconomic status were significant predictors of trajectory group membership. Implications for research and policy are discussed.",,"['Lowe, Sarah R.', 'Rhodes, Jean E.']",,,,
,PMC,Novel Benzoxazole Inhibitor of Dengue Virus Replication That Targets the NS3 Helicase,http://dx.doi.org/10.1128/AAC.02251-12,PMC3623359,,,"Dengue virus (DENV) is the predominant mosquito-borne viral pathogen that infects humans with an estimated 50 to 100 million infections per year worldwide. Over the past 50 years, the incidence of dengue disease has increased dramatically and the virus is now endemic in more than 100 countries. Moreover, multiple serotypes of DENV are now found in the same geographic region, increasing the likelihood of more severe forms of disease. Despite extensive research, there are still no approved vaccines or therapeutics commercially available to treat DENV infection. Here we report the results of a high-throughput screen of a chemical compound library using a whole-virus assay that identified a novel small-molecule inhibitor of DENV, ST-610, that potently and selectively inhibits all four serotypes of DENV replication in vitro. Sequence analysis of drug-resistant virus isolates has identified a single point mutation, A263T, in the NS3 helicase domain that confers resistance to this compound. ST-610 inhibits DENV NS3 helicase RNA unwinding activity in a molecular-beacon-based helicase assay but does not inhibit nucleoside triphosphatase activity based on a malachite green ATPase assay. ST-610 is nonmutagenic, is well tolerated (nontoxic) in mice, and has shown efficacy in a sublethal murine model of DENV infection with the ability to significantly reduce viremia and viral load compared to vehicle controls.",,"['Byrd, Chelsea M.', 'Grosenbach, Douglas W.', 'Berhanu, Aklile', 'Dai, Dongcheng', 'Jones, Kevin F.', 'Cardwell, Kara B.', 'Schneider, Christine', 'Yang, Guang', 'Tyavanagimatt, Shanthakumar', 'Harver, Chris', 'Wineinger, Kristin A.', 'Page, Jessica', 'Stavale, Eric', 'Stone, Melialani A.', 'Fuller, Kathleen P.', 'Lovejoy, Candace', 'Leeds, Janet M.', 'Hruby, Dennis E.', 'Jordan, Robert']",,,,
,PMC,Panmictic Structure of the Cryptosporidium parvum Population in Irish Calves: Influence of Prevalence and Host Movement,http://dx.doi.org/10.1128/AEM.03613-12,PMC3623186,,,"In total, 245 Cryptosporidium parvum specimens obtained from calves in 205 Irish herds between 2003 and 2005 were subtyped by sequencing the glycoprotein gene gp60 and performing multilocus analysis of seven markers. The transmission dynamics of C. parvum and the influence of temporal, spatial, parasitic, and host-related factors on the parasite (sub)populations were studied. The relationship of those factors to the risk of cryptosporidiosis was also investigated using results from 1,368 fecal specimens submitted to the veterinary laboratories for routine diagnosis during 2005. The prevalence was greatest in the northwest and midwest of the country and on farms that bought in calves. The panmixia (random mating) detected in the C. parvum population may relate to its high prevalence, the cattle density, and the frequent movement of cattle. However, local variations in these factors were reflected in the C. parvum subpopulations. This study demonstrated the importance of biosecurity in the control of bovine cryptosporidiosis (e.g., isolation and testing of calves before introduction into a herd). Furthermore, the zoonotic risk of C. parvum was confirmed, as most specimens possessed GP60 and MS1 subtypes previously described in humans.",,"['De Waele, Valérie', 'Van den Broeck, Frederik', 'Huyse, Tine', 'McGrath, Guy', 'Higgins, Isabella', 'Speybroeck, Niko', 'Berzano, Marco', 'Raleigh, Pat', 'Mulcahy, Grace M.', 'Murphy, Thomas M.']",,,,
,PMC,Is self-sufficiency in haemotherapies a practical or necessary goal?,http://dx.doi.org/10.2450/2012.0148-12,PMC3626469,,,,,"['Farrugia, Albert', 'Cassar, Josephine']",,,,
,PMC,A method to quantify infectious airborne pathogens at concentrations below the threshold of quantification by culture,,PMC3605936,,,"In aerobiology, dose-response studies are used to estimate the risk of infection to a susceptible host presented by exposure to a specific dose of an airborne pathogen. In the research setting, host- and pathogen-specific factors that affect the dose-response continuum can be accounted for by experimental design, but the requirement to precisely determine the dose of infectious pathogen to which the host was exposed is often challenging. By definition, quantification of viable airborne pathogens is based on the culture of micro-organisms, but some airborne pathogens are transmissible at concentrations below the threshold of quantification by culture. In this paper we present an approach to the calculation of exposure dose at microbiologically unquantifiable levels using an application of the “continuous-stirred tank reactor (CSTR) model” and the validation of this approach using rhodamine B dye as a surrogate for aerosolized microbial pathogens in a dynamic aerosol toroid (DAT).",,"['Cutler, Timothy D.', 'Wang, Chong', 'Hoff, Steven J.', 'Zimmerman, Jeffrey J.']",,,,
,PMC,Adjuvanticity of a Recombinant Calreticulin Fragment in Assisting Anti-β-Glucan IgG Responses in T Cell-Deficient Mice,http://dx.doi.org/10.1128/CVI.00689-12,PMC3623425,,,"Polysaccharide-encapsulated fungi are the chief source of diseases in immunocompromised hosts such as those infected with human immunodeficiency virus or neutropenia patients. Currently available polysaccharide-protein conjugate vaccines are mainly T cell dependent and are usually ineffective in weakened immune systems. In this study, laminarin, a well-characterized β-1,3-glucan, was conjugated with a prokaryotically expressed recombinant fragment (amino acids [aa] 39 to 272) of calreticulin (rCRT/39–272), which exhibits extraordinarily potent immunogenicity and adjuvanticity in experimental animals. The resultant conjugate reserves the immunostimulatory effect of rCRT/39–272 on naïve murine B cells and is capable of eliciting anti-β-glucan IgG (mostly IgG1) responses in not only BALB/c mice but also athymic nude mice. Laminarin-CRT-induced mouse antibodies (Abs) are able to bind with Candida albicans and inhibit its growth in vitro. In addition, vaccination with laminarin-CRT partially protects mice from lethal C. albicans challenge. These results imply that rCRT/39–272 could be used as an ideal carrier or adjuvant for carbohydrate vaccines aimed at inducing or boosting IgG responses to fungal infections in immunodeficient hosts.",,"['Li, Wei-Ji', 'Long, Kai', 'Dong, Hong-Liang', 'Gao, Xiao-Ming']",,,,
,PMC,A Novel Rat Model of Hereditary Hemochromatosis Due to a Mutation in Transferrin Receptor 2,,PMC3625055,,,"Sporadic iron overload in rats has been reported, but whether it is due to genetic or environmental causes is unknown. In the current study, phenotypic analysis of Hsd:HHCL Wistar rats revealed a low incidence of histologically detected liver iron overload. Here we characterized the pathophysiology of the iron overload and showed that the phenotype is heritable and due to a mutation in a single gene. We identified a single male rat among the 132 screened animals that exhibited predominantly periportal, hepatocellular iron accumulation. This rat expressed low RNA levels of the iron regulatory hormone hepcidin and low protein levels of transferrin receptor 2 (Tfr2), a membrane protein essential for hepcidin expression in humans and mice and mutated in forms of hereditary hemochromatosis. Sequencing of Tfr2 in the iron-overloaded rat revealed a novel Ala679Gly polymorphism in a highly conserved residue. Quantitative trait locus mapping indicated that this polymorphism correlated strongly with serum iron and transferrin saturations in male rats. Expression of the Gly679 variant in tissue culture cell lines revealed decreased steady-state levels of Tfr2. Characterization of iron metabolism in the progeny of polymorphic rats suggested that homozygosity for the Ala679Gly allele leads to a hemochromatosis phenotype. However, we currently cannot exclude the possibility that a polymorphism or mutation in the noncoding region of Tfr2 contributes to the iron-overload phenotype. Hsd:HHCL rats are the first genetic rat model of hereditary hemochromatosis and may prove useful for understanding the molecular mechanisms underlying the regulation of iron metabolism.",,"['Bartnikas, Thomas B', 'Wildt, Sheryl J', 'Wineinger, Amy E', 'Schmitz-Abe, Klaus', 'Markianos, Kyriacos', 'Cooper, Dale M', 'Fleming, Mark D']",,,,
,PMC,Overview of Protein Microarrays,http://dx.doi.org/10.1002/0471140864.ps2701s72,PMC3680110,,,"Protein microarray is an emerging technology that provides a versatile platform for characterization of hundreds of thousands of proteins in a highly parallel and high-throughput way. Two major classes of protein microarrays are defined to describe their applications: analytical and functional protein microarrays. In addition, tissue or cell lysates can also be fractionated and spotted on a slide to form a reverse-phase protein microarray. While the fabrication technology is maturing, applications of protein microarrays, especially functional protein microarrays, have flourished during the past decade. Here, we will first review recent advances in the protein microarray technologies, and then present a series of examples to illustrate the applications of analytical and functional protein microarrays in both basic and clinical research. The research areas will include detection of various binding properties of proteins, study of protein posttranslational modifications, analysis of host-microbe interactions, profiling antibody specificity, and identification of biomarkers in autoimmune diseases. As a powerful technology platform, it would not be surprising if protein microarrays will become one of the leading technologies in proteomic and diagnostic fields in the next decade.",,"['Reymond Sutandy, FX', 'Qian, Jiang', 'Chen, Chien-Sheng', 'Zhu, Heng']",,,,
,PMC,Comparison of a Multiplex Real-Time PCR Assay with a Multiplex Luminex Assay for Influenza Virus Detection,http://dx.doi.org/10.1128/JCM.03113-12,PMC3666787,,,"We describe the development of a multiplex reverse transcription-PCR (RT-PCR) with Luminex microarray hybridization for detection of influenza virus subtypes (FLULUM). Performance of FLULUM was evaluated by comparing it to our real-time RT-PCR influenza virus assay on samples collected during two influenza seasons. Both assays targeted the matrix genes of influenza virus A (FluA M) and influenza virus B (FluB M) and the hemagglutinin genes of seasonal H3N2 (H3) and H1N1 (H1) and 2009 pandemic H1N1 (2009 H1). We evaluated FLULUM on both the Luminex LX200 and the Luminex MagPix instruments. Compared to real-time PCR, FLULUM tested on 259 specimens submitted in the 2010-2011 season showed sensitivities of 97.3% for FluA M, 90.5% for 2009 H1, 96.9% for H3, and 88.9% for FluB M. No specimens were positive for seasonal H1. FLULUM tested on 806 specimens submitted in the 2011-2012 season showed a sensitivity of 100% for FluA M, 89.9% for 2009 H1, 96.4% for H3, and 95.6% for FluB M. No cross-reactivity was observed for other respiratory viruses. Analytical sensitivity was assessed by testing dilutions of specimens with high viral loads. The limits of detection of FLULUM were comparable to those of the real-time PCR assay for FluA M, FluB M, and H3. The limits of detection for seasonal H1 and 2009 H1 were 10-fold higher for the FLULUM assay compared to real-time PCR. The FLULUM is an economic assay with high clinical sensitivity and specificity. It is particularly suited to high-volume detection of influenza viruses.",,"['Munro, Sandra B.', 'Kuypers, Jane', 'Jerome, Keith R.']",,,,
,PMC,Detection and Genetic Diversity of Porcine Group A Rotaviruses in Historic (2004) and Recent (2011 and 2012) Swine Fecal Samples in Ohio: Predominance of the G9P[13] Genotype in Nursing Piglets,http://dx.doi.org/10.1128/JCM.03193-12,PMC3666770,,,"Epidemiological surveillance of porcine group A rotavirus (RVA) strains was conducted in five swine herds in Ohio using historical (2004) and recent (2011 to 2012) fecal samples. Of the 371 samples examined, 9.4% (35/371) were positive for RVA. The RVA detection rates increased from 5.9% in 2004 and 8.5% in 2011 to 13.8% in 2012. A total of 23 positive samples were analyzed for RVA G and P genotypes. The dominant G-P combination was G9P[13] found in 60.9% of positive samples. The other combinations were G9P[7] (8.7%), G4P[13] (8.7%), G11P[13] (4.3%), and G11P[7] (4.3%). Sequence analysis of partial VP7 genes of selected strains revealed that the G4 strains were closely related to one another (95%) and, to a lesser extent, to human (82 to 84%) and porcine (84 to 86%) G4 strains. The G11 strains detected shared identical VP7 gene sequences (100%) and were closely related to human (85 to 86%) and other porcine (83%) G11 strains. The G9 strains identified were closely related to one another and to human and other porcine strains (96 to 97%, 89 to 91%, and 89 to 91% nucleotide identities, respectively). The VP4 gene analysis revealed that P[7] strains were closely related to each other and to P[7] strains isolated from porcine, bovine, and panda samples (91 to 99%, 92 to 99% and 92 to 99%, respectively). The P[13] strains showed a higher diversity among themselves and with other porcine P[13] strains, ranging from 83% to 99% and from 82 to 97%, respectively. Our results demonstrate broad genetic heterogeneity of the RVA strains and suggest the possibility of genetic reassortment between different RVA genotypes within these farms.",,"['Amimo, J. O.', 'Vlasova, A. N.', 'Saif, L. J.']",,,,
,PMC,Comparison of Anyplex II RV16 with the xTAG Respiratory Viral Panel and Seeplex RV15 for Detection of Respiratory Viruses,http://dx.doi.org/10.1128/JCM.02958-12,PMC3666760,,,"A novel multiplex real-time PCR approach (Anyplex II RV16 [RV16]; Seegene, South Korea) was compared with a multiplex endpoint PCR kit (Seeplex RV15 ACE detection kit [RV15]; Seegene) and a liquid bead-based assay (xTAG respiratory viral panel [xTAG]; Abbott, United States). Of nasopharyngeal swabs or aspirates and bronchoalveolar lavage fluid samples submitted for RV15 testing, 199 retrospectively collected positive specimens and 283 prospectively collected specimens were further tested with RV16 and xTAG. A true-positive result was defined as a positive result from all three methods or RV16 and xTAG or RV15 and xTAG. For specimens with discrepant results, monoplex PCR and sequencing of the target viruses were performed. In total, 300 virus-positive specimens yielded 386 viruses. When the bocavirus results were excluded, the overall sensitivities of RV16, RV15, and xTAG were 95.2%, 93.3%, and 87.2%, respectively (95% confidence intervals, 93.0 to 97.4%, 90.8 to 95.8%, and 83.8 to 90.6%, respectively). RV16 was more sensitive than xTAG for coronavirus OC43/HKU1 (100% versus 26.1%; P < 0.0001) and adenovirus (100% versus 79.5%; P < 0.01) but was less sensitive than xTAG for rhinovirus/enterovirus (89.4% versus 97.9%; P < 0.05). RV16 demonstrated higher sensitivity than RV15 for the detection of adenovirus (100% versus 82.1%; P < 0.05). The specificities of all three methods ranged from 98.6% to 100%. Sequencing analysis of 64 rhinovirus-positive samples revealed that RV16 accurately differentiated between rhinovirus and enterovirus. RV16 most frequently missed rhinovirus C. In conclusion, the overall sensitivity of RV16 was better than that of xTAG. However, improvement of the sensitivity for rhinovirus is required.",,"['Kim, Hyun-Ki', 'Oh, Sung-Hee', 'Yun, Kyung Ah', 'Sung, Heungsup', 'Kim, Mi-Na']",,,,
,PMC,Novel mutations in Marburg virus glycoprotein associated with viral evasion from antibody mediated immune pressure,http://dx.doi.org/10.1099/vir.0.049114-0,PMC3709686,,,"Marburg virus (MARV) and Ebola virus, members of the family Filoviridae, cause lethal haemorrhagic fever in humans and non-human primates. Although the outbreaks are concentrated mainly in Central Africa, these viruses are potential agents of imported infectious diseases and bioterrorism in non-African countries. Recent studies demonstrated that non-human primates passively immunized with virus-specific antibodies were successfully protected against fatal filovirus infection, highlighting the important role of antibodies in protective immunity for this disease. However, the mechanisms underlying potential evasion from antibody mediated immune pressure are not well understood. To analyse possible mutations involved in immune evasion in the MARV envelope glycoprotein (GP) which is the major target of protective antibodies, we selected escape mutants of recombinant vesicular stomatitis virus (rVSV) expressing MARV GP (rVSVΔG/MARVGP) by using two GP-specific mAbs, AGP127-8 and MGP72-17, which have been previously shown to inhibit MARV budding. Interestingly, several rVSVΔG/MARVGP variants escaping from the mAb pressure-acquired amino acid substitutions in the furin-cleavage site rather than in the mAb-specific epitopes, suggesting that these epitopes are recessed, not exposed on the uncleaved GP molecule, and therefore inaccessible to the mAbs. More surprisingly, some variants escaping mAb MGP72-17 lacked a large proportion of the mucin-like region of GP, indicating that these mutants efficiently escaped the selective pressure by deleting the mucin-like region including the mAb-specific epitope. Our data demonstrate that MARV GP possesses the potential to evade antibody mediated immune pressure due to extraordinary structural flexibility and variability.",,"['Kajihara, Masahiro', 'Nakayama, Eri', 'Marzi, Andrea', 'Igarashi, Manabu', 'Feldmann, Heinz', 'Takada, Ayato']",,,,
,PMC,Overexpression of SIRT1 protein in neurons protects against Experimental Autoimmune Encephalomyelitis through activation of multiple SIRT1 targets,http://dx.doi.org/10.4049/jimmunol.1202584,PMC3963275,,,"Treatment of experimental autoimmune encephalomyelitis (EAE) with Resveratrol, an activator of Sirtuin 1 (SIRT1), reduces disease severity. This suggested that activators of SIRT1, a highly conserved nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase, might have immune-modulating or neuroprotective therapeutic effects in EAE. Previously, we showed that SIRT1 expression increases in EAE, suggesting that it is an adaptive response. In this study, we investigated the potential function of SIRT1 in regulating EAE using SIRT1 overexpressing mice. The current studies examine potential neuroprotective and immunomodulatory effects of SIRT1 overexpression in chronic EAE induced by immunization of C57Bl/6 mice with myelin oligodendrocyte glycoprotein peptide (MOG(35-55)). SIRT1 suppressed EAE clinical symptoms compared with wild-type EAE mice and prevented or altered the phenotype of inflammation in spinal cords; as a result, demyelination and axonal injury were reduced. Significant neuroprotective effects were observed, with fewer apoptotic cells found in the spinal cords of SIRT1 overexpressing EAE mice; associated with increased brain-derived neurotrophic factor (BDNF) and NAD levels. Earlier, we showed that BDNF and NAD play crucial neuroprotective roles in EAE. These results suggest that SIRT1 reduces neuronal loss in this chronic demyelinating disease model and that this is associated with a reduction in inflammation.",,"['Nimmagadda, Vamshi K.', 'Bever, Christopher T.', 'Vattikunta, Narasimha R.', 'Talat, Saifi', 'Ahmad, Vakas', 'Nagalla, Naveen K.', 'Trisler, David', 'Judge, Susan I. V.', 'Royal, Walter', 'Chandrasekaran, Krish', 'Russell, James W.', 'Makar, Tapas K.']",,,,
,PMC,A Death-Promoting Role for ISG54/IFIT2,http://dx.doi.org/10.1089/jir.2012.0159,PMC3624773,,,"The cellular responses to infection are many, and include programmed cell death to inhibit microbial dissemination and the production and secretion of interferons (IFNs), which confer resistance to uninfected cells. In addition to the antimicrobial effects of IFNs, these cytokines have been used clinically for the treatment of various neoplasias to inhibit proliferation and stimulate apoptosis. However, the precise mechanisms of action of IFNs remain to be completely understood. One of the primary response genes induced after an infection or treatment with type I or III IFN is known as IFN-stimulated gene 54 (ISG54) or IFN-induced gene with tetratricopeptide repeats 2 (IFIT2). ISG54/IFIT2 is a member of a family of IFN-induced genes related in the sequence and structure. Expression of this protein has been found to promote cellular apoptosis by a mitochondrial pathway dependent on the action of Bcl2 proteins. ISG54/IFIT2 does not function as a monomer, and it forms complexes with itself and with the related ISG56/IFIT1 and ISG60/IFIT3 proteins to elicit complex cellular responses. The apoptotic response to ISG54/IFIT2 may contribute to other functions that have been reported, including translational regulation, inhibition of tumor colonization, and protection against a lethal viral infection.",,"Reich, Nancy C.",,,,
,PMC,A novel approach to oral apoA-I mimetic therapy,http://dx.doi.org/10.1194/jlr.M033555,PMC3606004,,,"Transgenic tomato plants were constructed with an empty vector (EV) or a vector expressing an apoA-I mimetic peptide, 6F. EV or 6F tomatoes were harvested, lyophilized, ground into powder, added to Western diet (WD) at 2.2% by weight, and fed to LDL receptor-null (LDLR(−/−)) mice at 45 mg/kg/day 6F. After 13 weeks, the percent of the aorta with lesions was 4.1 ± 4%, 3.3 ± 2.4%, and 1.9 ± 1.4% for WD, WD + EV, and WD + 6F, respectively (WD + 6F vs. WD, P = 0.0134; WD + 6F vs. WD + EV, P = 0.0386; WD + EV vs. WD, not significant). While body weight did not differ, plasma serum amyloid A (SAA), total cholesterol, triglycerides, and lysophosphatidic acid (LPA) levels were less in WD + 6F mice; P < 0.0295. HDL cholesterol and paroxonase-1 activity (PON) were higher in WD + 6F mice (P = 0.0055 and P = 0.0254, respectively), but not in WD + EV mice. Plasma SAA, total cholesterol, triglycerides, LPA, and 15-hydroxyeicosatetraenoic acid (HETE) levels positively correlated with lesions (P < 0.0001); HDL cholesterol and PON were inversely correlated (P < 0.0001). After feeding WD + 6F: i) intact 6F was detected in small intestine (but not in plasma); ii) small intestine LPA was decreased compared with WD + EV (P < 0.0469); and iii) small intestine LPA 18:2 positively correlated with the percent of the aorta with lesions (P < 0.0179). These data suggest that 6F acts in the small intestine and provides a novel approach to oral apoA-I mimetic therapy.",,"['Chattopadhyay, Arnab', 'Navab, Mohamad', 'Hough, Greg', 'Gao, Feng', 'Meriwether, David', 'Grijalva, Victor', 'Springstead, James R.', 'Palgnachari, Mayakonda N.', 'Namiri-Kalantari, Ryan', 'Su, Feng', 'Van Lenten, Brian J.', 'Wagner, Alan C.', 'Anantharamaiah, G. M.', 'Farias-Eisner, Robin', 'Reddy, Srinivasa T.', 'Fogelman, Alan M.']",,,,
,PMC,Severe Fever with Thrombocytopenia Virus Glycoproteins Are Targeted by Neutralizing Antibodies and Can Use DC-SIGN as a Receptor for pH-Dependent Entry into Human and Animal Cell Lines,http://dx.doi.org/10.1128/JVI.02628-12,PMC3624395,,,"Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel bunyavirus that recently emerged in China. Infection with SFTSV is associated with case-fatality rates of up to 30%, and neither antivirals nor vaccines are available at present. Development of antiviral strategies requires the elucidation of virus-host cell interactions. Here, we analyzed host cell entry of SFTSV. Employing lentiviral and rhabdoviral vectors, we found that the Gn/Gc glycoproteins (Gn/Gc) of SFTSV mediate entry into a broad range of human and animal cell lines, as well as human macrophages and dendritic cells. The Gn/Gc proteins of La Crosse virus (LACV) and Rift Valley Fever Virus (RVFV), other members of the bunyavirus family, facilitated entry into an overlapping but not identical range of cell lines, suggesting that SFTSV, LACV, and RVFV might differ in their receptor requirements. Entry driven by SFTSV Gn/Gc was dependent on low pH but did not require the activity of the pH-dependent endosomal/lysosomal cysteine proteases cathepsins B and L. Instead, the activity of a cellular serine protease was required for infection driven by SFTSV and LACV Gn/Gc. Sera from convalescent SFTS patients inhibited SFTSV Gn/Gc-driven host cell entry in a dose-dependent fashion, demonstrating that the vector system employed is suitable to detect neutralizing antibodies. Finally, the C-type lectin DC-SIGN was found to serve as a receptor for SFTSV Gn/Gc-driven entry into cell lines and dendritic cells. Our results provide initial insights into cell tropism, receptor usage, and proteolytic activation of SFTSV and will aid in the understanding of viral spread and pathogenesis.",,"['Hofmann, Heike', 'Li, Xingxing', 'Zhang, Xiaoai', 'Liu, Wei', 'Kühl, Annika', 'Kaup, Franziska', 'Soldan, Samantha S.', 'González-Scarano, Francisco', 'Weber, Friedemann', 'He, Yuxian', 'Pöhlmann, Stefan']",,,,
,PMC,Structural Basis of Substrate Specificity and Protease Inhibition in Norwalk Virus,http://dx.doi.org/10.1128/JVI.02869-12,PMC3624372,,,"Norwalk virus (NV), the prototype human calicivirus, is the leading cause of nonbacterial acute gastroenteritis. The NV protease cleaves the polyprotein encoded by open reading frame 1 of the viral genome at five nonhomologous sites, releasing six nonstructural proteins that are essential for viral replication. The structural details of how NV protease recognizes multiple substrates are unclear. In our X-ray structure of an NV protease construct, we observed that the C-terminal tail, representing the native substrate positions P5 to P1, is inserted into the active site cleft of the neighboring protease molecule, providing atomic details of how NV protease recognizes a substrate. The crystallographic structure of NV protease with the C-terminal tail redesigned to mimic P4 to P1 of another substrate site provided further structural details on how the active site accommodates sequence variations in the substrates. Based on these structural analyses, substrate-based aldehyde inhibitors were synthesized and screened for inhibition potency. Crystallographic structures of the protease in complex with each of the three most potent inhibitors were determined. These structures showed concerted conformational changes in the S4 and S2 pockets of the protease to accommodate variations in the P4 and P2 residues of the substrate/inhibitor, which could be a mechanism for how the NV protease recognizes multiple sites in the polyprotein with differential affinities during virus replication. These structures further indicate that the mechanism of inhibition by these inhibitors involves covalent bond formation with the side chain of the conserved cysteine in the active site by nucleophilic addition, and such substrate-based aldehydes could be effective protease inhibitors.",,"['Muhaxhiri, Zana', 'Deng, Lisheng', 'Shanker, Sreejesh', 'Sankaran, Banumathi', 'Estes, Mary K.', 'Palzkill, Timothy', 'Song, Yongcheng', 'Prasad, B. V. Venkataram']",,,,
,PMC,3C Protease of Enterovirus 68: Structure-Based Design of Michael Acceptor Inhibitors and Their Broad-Spectrum Antiviral Effects against Picornaviruses,http://dx.doi.org/10.1128/JVI.01123-12,PMC3624371,,,"We have determined the cleavage specificity and the crystal structure of the 3C protease of enterovirus 68 (EV68 3C(pro)). The protease exhibits a typical chymotrypsin fold with a Cys...His...Glu catalytic triad; its three-dimensional structure is closely related to that of the 3C(pro) of rhinovirus 2, as well as to that of poliovirus. The phylogenetic position of the EV68 3C(pro) between the corresponding enzymes of rhinoviruses on the one hand and classical enteroviruses on the other prompted us to use the crystal structure for the design of irreversible inhibitors, with the goal of discovering broad-spectrum antiviral compounds. We synthesized a series of peptidic α,β-unsaturated ethyl esters of increasing length and for each inhibitor candidate, we determined a crystal structure of its complex with the EV68 3C(pro), which served as the basis for the next design round. To exhibit inhibitory activity, compounds must span at least P3 to P1′; the most potent inhibitors comprise P4 to P1′. Inhibitory activities were found against the purified 3C protease of EV68, as well as with replicons for poliovirus and EV71 (50% effective concentration [EC(50)] = 0.5 μM for the best compound). Antiviral activities were determined using cell cultures infected with EV71, poliovirus, echovirus 11, and various rhinovirus serotypes. The most potent inhibitor, SG85, exhibited activity with EC(50)s of ≈180 nM against EV71 and ≈60 nM against human rhinovirus 14 in a live virus–cell-based assay. Even the shorter SG75, spanning only P3 to P1′, displayed significant activity (EC(50) = 2 to 5 μM) against various rhinoviruses.",,"['Tan, Jinzhi', 'George, Shyla', 'Kusov, Yuri', 'Perbandt, Markus', 'Anemüller, Stefan', 'Mesters, Jeroen R.', 'Norder, Helene', 'Coutard, Bruno', 'Lacroix, Céline', 'Leyssen, Pieter', 'Neyts, Johan', 'Hilgenfeld, Rolf']",,,,
,PMC,Matriptase Proteolytically Activates Influenza Virus and Promotes Multicycle Replication in the Human Airway Epithelium,http://dx.doi.org/10.1128/JVI.03005-12,PMC3624356,,,"Influenza viruses do not encode any proteases and must rely on host proteases for the proteolytic activation of their surface hemagglutinin proteins in order to fuse with the infected host cells. Recent progress in the understanding of human proteases responsible for influenza virus hemagglutinin activation has led to the identification of members of the type II transmembrane serine proteases TMPRSS2 and TMPRSS4 and human airway trypsin-like protease; however, none has proved to be the sole enzyme responsible for hemagglutinin cleavage. In this study, we identify and characterize matriptase as an influenza virus-activating protease capable of supporting multicycle viral replication in the human respiratory epithelium. Using confocal microscopy, we found matriptase to colocalize with hemagglutinin at the apical surface of human epithelial cells and within endosomes, and we showed that the soluble form of the protease was able to specifically cleave hemagglutinins from H1 virus, but not from H2 and H3 viruses, in a broad pH range. We showed that small interfering RNA (siRNA) knockdown of matriptase in human bronchial epithelial cells significantly blocked influenza virus replication in these cells. Lastly, we provide a selective, slow, tight-binding inhibitor of matriptase that significantly reduces viral replication (by 1.5 log) of H1N1 influenza virus, including the 2009 pandemic virus. Our study establishes a three-pronged model for the action of matriptase: activation of incoming viruses in the extracellular space in its shed form, upon viral attachment or exit in its membrane-bound and/or shed forms at the apical surface of epithelial cells, and within endosomes by its membrane-bound form where viral fusion takes place.",,"['Beaulieu, Alexandre', 'Gravel, Émilie', 'Cloutier, Alexandre', 'Marois, Isabelle', 'Colombo, Éloïc', 'Désilets, Antoine', 'Verreault, Catherine', 'Leduc, Richard', 'Marsault, Éric', 'Richter, Martin V.']",,,,
,PMC,Diversity of Ubiquitin and ISG15 Specificity among Nairoviruses' Viral Ovarian Tumor Domain Proteases,http://dx.doi.org/10.1128/JVI.03252-12,PMC3624237,,,"Nairoviruses are responsible for numerous diseases that affect both humans and animal. Recent work has implicated the viral ovarian tumor domain (vOTU) as a possible nairovirus virulence factor due to its ability to edit ubiquitin (Ub) bound to cellular proteins and, at least in the case of Crimean-Congo hemorrhagic fever virus (CCHFV), to cleave the Ub-like protein interferon-stimulated gene 15 (ISG15), a protein involved in the regulation of host immunity. The prospective roles of vOTUs in immune evasion have generated several questions concerning whether vOTUs act through a preserved specificity for Ub- and ISG15-conjugated proteins and where that specificity may originate. To gain insight into the substrate specificity of vOTUs, enzymological studies were conducted on vOTUs from Dugbe, CCHFV, and Erve nairoviruses. These studies revealed that vOTUs originating from different nairoviruses display a significant divergence in their preference toward Ub and ISG15. In addition, a recently identified vOTU from turnip yellow mosaic tymovirus was evaluated to elucidate any possible similarities between vOTUs originating from different viral families. Although possessing a similar preference for certain polymeric Ub moieties, its activity toward Ub in general was significantly less then those of nairoviruses. Lastly, the X-ray crystallographic structure of the vOTU from the Dugbe nairovirus was obtained in complex with Ub to reveal structural commonalities of vOTUs originating from nairoviruses. The structure suggests that divergences between nairovirus vOTUs specificity originate at the primary structural level. Comparison of this structure to that originating from CCHFV identified key residues that infer the substrate specificity of vOTUs.",,"['Capodagli, Glenn C.', 'Deaton, Michelle K.', 'Baker, Erica A.', 'Lumpkin, Ryan J.', 'Pegan, Scott D.']",,,,
,PMC,In Vitro Modeling of Human Bocavirus 1 Infection of Polarized Primary Human Airway Epithelia,http://dx.doi.org/10.1128/JVI.03132-12,PMC3624236,,,"Human bocavirus 1 (HBoV1) is an emerging human-pathogenic respiratory virus. We characterized two important features of HBoV1 infection in polarized primary human airway epithelia (HAE). Apical HBoV1 infection of HAE at a low multiplicity of infection causes disruption of the tight junction barrier, loss of cilia, and epithelial cell hypertrophy, which are hallmarks of the airway epithelial damage caused by HBoV1 infection. HBoV1 also infects HAE from the basolateral surface productively, although less efficiently, and this also leads to the characteristic airway epithelial damage.",,"['Deng, Xuefeng', 'Yan, Ziying', 'Luo, Yong', 'Xu, Jian', 'Cheng, Fang', 'Li, Yi', 'Engelhardt, John F.', 'Qiu, Jianming']",,,,
,PMC,Structural Analysis of the Evolutionary Origins of Influenza Virus Hemagglutinin and Other Viral Lectins,http://dx.doi.org/10.1128/JVI.03476-12,PMC3624229,,,"Influenza virus and other viruses use host cell surface sugars as receptors. Here we show that the sugar-binding domains in influenza virus hemagglutinin and other viral lectins share the same structural fold as human galectins (host lectins). Unlike the easily accessible sugar-binding sites in human galectins, the sugar-binding sites in viral lectins are hidden in cavities. We propose that these viral lectins originated from host lectins but have evolved to use hidden sugar-binding sites to evade host immune attacks.",,"['Chen, Lang', 'Li, Fang']",,,,
,PMC,Measles Virus Infection of Epithelial Cells in the Macaque Upper Respiratory Tract Is Mediated by Subepithelial Immune Cells,http://dx.doi.org/10.1128/JVI.03258-12,PMC3624209,,,"Measles virus (MV), one of the most contagious viruses infecting humans, causes a systemic infection leading to fever, immune suppression, and a characteristic maculopapular rash. However, the specific mechanism or mechanisms responsible for the spread of MV into the respiratory epithelium in the late stages of the disease are unknown. Here we show the crucial role of PVRL4 in mediating the spread of MV from immune to epithelial cells by generating a PVRL4 “blind” recombinant wild-type MV and developing a novel in vitro coculture model of B cells with primary differentiated normal human bronchial epithelial cells. We utilized the macaque model of measles to analyze virus distribution in the respiratory tract prior to and at the peak of MV replication. Expression of PVRL4 was widespread in both the lower and upper respiratory tract (URT) of macaques, indicating MV transmission can be facilitated by more than only epithelial cells of the trachea. Analysis of tissues collected at early time points after experimental MV infection demonstrated the presence of MV-infected lymphoid and myeloid cells contacting respiratory tract epithelium in the absence of infected epithelial cells, suggesting that these immune cells seed the infection in vivo. Thereafter, lateral cell-to-cell spread of MV led to the formation of large foci of infected cells in the trachea and high levels of MV infection in the URT, particularly in the nasal cavity. These novel findings have important implications for our understanding of the high transmissibility of measles.",,"['Ludlow, Martin', 'Lemon, Ken', 'de Vries, Rory D.', 'McQuaid, Stephen', 'Millar, Emma L.', 'van Amerongen, Geert', 'Yüksel, Selma', 'Verburgh, R. Joyce', 'Osterhaus, Albert D. M. E.', 'de Swart, Rik L.', 'Duprex, W. Paul']",,,,
,PMC,Ebola Virus Exploits a Monocyte Differentiation Program To Promote Its Entry,http://dx.doi.org/10.1128/JVI.02695-12,PMC3624207,,,"Antigen-presenting cells (APCs) are critical targets of Ebola virus (EBOV) infection in vivo. However, the susceptibility of monocytes to infection is controversial. Studies indicate productive monocyte infection, and yet monocytes are also reported to be resistant to EBOV GP-mediated entry. In contrast, monocyte-derived macrophages and dendritic cells are permissive for both EBOV entry and replication. Here, freshly isolated monocytes are demonstrated to indeed be refractory to EBOV entry. However, EBOV binds monocytes, and delayed entry occurs during monocyte differentiation. Cultured monocytes spontaneously downregulate the expression of viral entry restriction factors such as interferon-inducible transmembrane proteins, while upregulating the expression of critical EBOV entry factors cathepsin B and NPC1. Moreover, these processes are accelerated by EBOV infection. Finally, ectopic expression of NPC1 is sufficient to rescue entry into an undifferentiated, normally nonpermissive monocytic cell line. These results define the molecular basis for infection of APCs and suggest means to limit APC infection.",,"['Martinez, Osvaldo', 'Johnson, Joshua C.', 'Honko, Anna', 'Yen, Benjamin', 'Shabman, Reed S.', 'Hensley, Lisa E.', 'Olinger, Gene G.', 'Basler, Christopher F.']",,,,
,PMC,Release of Severe Acute Respiratory Syndrome Coronavirus Nuclear Import Block Enhances Host Transcription in Human Lung Cells,http://dx.doi.org/10.1128/JVI.02520-12,PMC3624188,,,"The severe acute respiratory syndrome coronavirus accessory protein ORF6 antagonizes interferon signaling by blocking karyopherin-mediated nuclear import processes. Viral nuclear import antagonists, expressed by several highly pathogenic RNA viruses, likely mediate pleiotropic effects on host gene expression, presumably interfering with transcription factors, cytokines, hormones, and/or signaling cascades that occur in response to infection. By bioinformatic and systems biology approaches, we evaluated the impact of nuclear import antagonism on host expression networks by using human lung epithelial cells infected with either wild-type virus or a mutant that does not express ORF6 protein. Microarray analysis revealed significant changes in differential gene expression, with approximately twice as many upregulated genes in the mutant virus samples by 48 h postinfection, despite identical viral titers. Our data demonstrated that ORF6 protein expression attenuates the activity of numerous karyopherin-dependent host transcription factors (VDR, CREB1, SMAD4, p53, EpasI, and Oct3/4) that are critical for establishing antiviral responses and regulating key host responses during virus infection. Results were confirmed by proteomic and chromatin immunoprecipitation assay analyses and in parallel microarray studies using infected primary human airway epithelial cell cultures. The data strongly support the hypothesis that viral antagonists of nuclear import actively manipulate host responses in specific hierarchical patterns, contributing to the viral pathogenic potential in vivo. Importantly, these studies and modeling approaches not only provide templates for evaluating virus antagonism of nuclear import processes but also can reveal candidate cellular genes and pathways that may significantly influence disease outcomes following severe acute respiratory syndrome coronavirus infection in vivo.",,"['Sims, Amy C.', 'Tilton, Susan C.', 'Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Schäfer, Alexandra', 'Matzke, Melissa M.', 'Webb-Robertson, Bobbie-Jo M.', 'Chang, Jean', 'Luna, Maria L.', 'Long, Casey E.', 'Shukla, Anil K.', 'Bankhead, Armand R.', 'Burkett, Susan E.', 'Zornetzer, Gregory', 'Tseng, Chien-Te Kent', 'Metz, Thomas O.', 'Pickles, Raymond', 'McWeeney, Shannon', 'Smith, Richard D.', 'Katze, Michael G.', 'Waters, Katrina M.', 'Baric, Ralph S.']",,,,
,PMC,A human astrocytoma cell line is highly susceptible to infection with Trypanosoma cruzi,http://dx.doi.org/10.1590/0074-0276108022013014,PMC3970672,,,"Astrocytes play a vital role in neuronal protection, homeostasis, vascular interchange and the local immune response. Some viruses and parasites can cross the blood-brain barrier and infect glia. Trypanosoma cruzi, the aetiological agent of Chagas disease, can seriously compromise the central nervous system, mainly in immune-suppressed individuals, but also during the acute phase of the infection. In this report, the infective capacity of T. cruzi in a human astrocyte tumour-derived cell line was studied. Astrocytes exposed to trypomastigotes (1:10 ratio) produced intracellular amastigotes and new trypomastigotes emerged by day 4 post-infection (p.i.). At day 6 p.i., 93% of the cells were infected. Using flow cytometry, changes were observed in both the expression of major histocompatibility complex class I and II molecules and the chemokine secretion pattern of astrocytes exposed to the parasite. Blocking the low-density lipoprotein receptor on astrocytes did not reduce parasite intracellular infection. Thus, T. cruzi can infect astrocytes and modulate the immune response during central nervous system infection.",,"['Vargas-Zambrano, Juan Camilo', 'Lasso, Paola', 'Cuellar, Adriana', 'Puerta, Concepción Judith', 'González, John Mario']",,,,
,PMC,Panel 5: Microbiology and Immunology Panel,http://dx.doi.org/10.1177/0194599812459636,PMC4021594,,,"OBJECTIVE: The objective is to perform a comprehensive review of the literature from January 2007 through June 2011 on the virology, bacteriology, and immunology related to otitis media. DATA SOURCES: PubMed database of the National Library of Medicine. REVIEW METHODS: Three subpanels with co-chairs comprising experts in the virology, bacteriology, and immunology of otitis media were formed. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a second draft was created. The entire panel met at the 10th International Symposium on Recent Advances in Otitis Media in June 2011 and discussed the review and refined the content further. A final draft was created, circulated, and approved by the panel. CONCLUSION: Excellent progress has been made in the past 4 years in advancing an understanding of the microbiology and immunology of otitis media. Advances include laboratory-based basic studies, cell-based assays, work in animal models, and clinical studies. IMPLICATIONS FOR PRACTICE: The advances of the past 4 years formed the basis of a series of short-term and long-term research goals in an effort to guide the field. Accomplishing these goals will provide opportunities for the development of novel interventions, including new ways to better treat and prevent otitis media.",,"['Murphy, Timothy F.', 'Chonmaitree, Tasnee', 'Barenkamp, Stephen', 'Kyd, Jennelle', 'Nokso-Koivisto, Johanna', 'Patel, Janak A.', 'Heikkinen, Terho', 'Yamanaka, Noboru', 'Ogra, Pearay', 'Swords, W. Edward', 'Sih, Tania', 'Pettigrew, Melinda M.']",,,,
,PMC,OT-1 Mice Display Minimal Upper Genital Tract Pathology Following Primary Intravaginal Chlamydia muridarum Infection,http://dx.doi.org/10.1111/2049-632X.12032,PMC3641702,,,"Chlamydia trachomatis is the most common bacterial sexually transmitted disease worldwide and leads to serious pathological sequelae in the upper genital tract (UGT) including pelvic inflammatory disease, ectopic pregnancy, and infertility. Several components of the host immune responses have been shown to contribute to the UGT pathology following genital chlamydial infection. We have shown recently that CD8(+) T cells induce the chlamydial UGT pathology via the production of TNF-α. However, those studies did not determine whether the pathology is mediated by bystander or antigen-specific CD8(+) T cells. In this study, we compared chlamydial clearance and UGT pathology in OT-1 transgenic mice and the corresponding C57BL/6J wild type mice following primary intravaginal C. muridarum infection. All CD8(+) T cells in the OT-1 mice respond only to the Ova 257–264 peptide and are incapable of responding to other antigenic epitopes including those of Chlamydia. OT-1 mice displayed vaginal chlamydial clearance comparable to the wild type animals. However, both oviduct and uterine horn pathology were minimal in the OT-1 mice compared to the high degree of pathology observed in the wild type animals. These results strongly suggest that Chlamydia-specific, not bystander, CD8(+) T cells mediate the UGT pathological sequelae following genital chlamydial infection.",,"['Manam, Srikanth', 'Nicholson, Bruce J.', 'Murthy, Ashlesh K.']",,,,
,PMC,Seasonality of Acute Otitis Media and the Role of Respiratory Viral Activity in Children,http://dx.doi.org/10.1097/INF.0b013e31827d104e,PMC3618601,,,"BACKGROUND: Acute otitis media (AOM) occurs as a complication of viral upper respiratory tract infections in young children. AOM and respiratory viruses both display seasonal variation. Our objective was to examine the temporal association between circulating respiratory viruses and the occurrence of pediatric ambulatory care visits for AOM. METHODS: This retrospective study included 9 seasons of respiratory viral activity (2002-2010) in Utah. We used Intermountain Healthcare's electronic medical records to assess community respiratory viral activity via laboratory-based active surveillance and to identify children <18 years with outpatient visits and ICD-9 codes for AOM. We assessed the strength of the association between AOM and individual respiratory viruses using interrupted time series analyses. RESULTS: During the study period, 96,418 respiratory viral tests were performed; 46,460 (48%) were positive. The most commonly identified viruses were: RSV (22%), rhinovirus (8%), influenza (8%), parainfluenza (4%), human metapneumovirus (3%), and adenovirus (3%). AOM was diagnosed during 271,268 ambulatory visits. There were significant associations between peak activity of RSV, human metapneumovirus, influenza A, and office visits for AOM. Adenovirus, parainfluenza, and rhinovirus were not associated with visits for AOM. CONCLUSIONS: Seasonal RSV, human metapneumovirus, and influenza activity were temporally associated with increased diagnoses of AOM among children. These findings support the role of individual respiratory viruses in the development AOM. These data also underscore the potential for respiratory viral vaccines to reduce the burden of AOM.",,"['Stockmann, Chris', 'Ampofo, Krow', 'Hersh, Adam L.', 'Carleton, Scott T.', 'Korgenski, Kent', 'Sheng, Xiaoming', 'Pavia, Andrew T.', 'Byington, Carrie L.']",,,,
,PMC,Identification of RNA partners of viral proteins in infected cells,http://dx.doi.org/10.4161/rna.24453,PMC4111734,,,"RNA viruses exhibit small-sized genomes encoding few proteins, but still establish complex networks of protein-protein and RNA-protein interactions within a cell to achieve efficient replication and spreading. Deciphering these interactions is essential to reach a comprehensive understanding of the viral infection process. To study RNA-protein complexes directly in infected cells, we developed a new approach based on recombinant viruses expressing tagged viral proteins that were purified together with their specific RNA partners. High-throughput sequencing was then used to identify these RNA molecules. As a proof of principle, this method was applied to measles virus nucleoprotein (MV-N). It revealed that in addition to full-length genomes, MV-N specifically interacted with a unique population of 5′ copy-back defective interfering RNA genomes that we characterized. Such RNA molecules were able to induce strong activation of interferon-stimulated response element promoter preferentially via the cytoplasmic pattern recognition receptor RIG-I protein, demonstrating their biological functionality. Thus, this method provides a new platform to explore biologically active RNA-protein networks that viruses establish within infected cells.",,"['Komarova, Anastassia V.', 'Combredet, Chantal', 'Sismeiro, Odile', 'Dillies, Marie-Agnès', 'Jagla, Bernd', 'Sanchez David, Raul Yusef', 'Vabret, Nicolas', 'Coppée, Jean-Yves', 'Vidalain, Pierre-Olivier', 'Tangy, Frédéric']",,,,
,PMC,Immunogenicity and Protection Efficacy of Monomeric and Trimeric Recombinant SARS Coronavirus Spike Protein Subunit Vaccine Candidates,http://dx.doi.org/10.1089/vim.2012.0076,PMC3624630,,,"Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease, and an effective vaccine is not available. In this study, we compared the immunogenicity and protection efficacy of recombinant proteins corresponding to different domains of the SARS-coronavirus spike protein. Trimeric recombinant proteins were created by fusing the foldon domain derived from T4 bacteriophage to the carboxy-termini of individual domains of the spike protein. While the full-length ectodomain (S) of the spike protein, the full-length ectodomain fused to foldon (S-foldon), the S1 domain (S1), S1-foldon, and the S2 domain(S2) antigens all elicited comparable antibody titers as measured by ELISA, S-foldon induced a significantly higher titer of neutralizing antibody and S2 protein did not elicit virus neutralizing antibodies. When tested in a mouse virus replication model, all the mice vaccinated with the S1, S1-foldon, S, or S-foldon were completely protected.",,"['Li, Jie', 'Ulitzky, Laura', 'Silberstein, Erica', 'Taylor, Deborah R.', 'Viscidi, Raphael']",,,,
,PMC,Entry and exit screening of airline travellers during the A(H1N1) 2009 pandemic: a retrospective evaluation,http://dx.doi.org/10.2471/BLT.12.114777,PMC3646347,,,"OBJECTIVE: To evaluate the screening measures that would have been required to assess all travellers at risk of transporting A(H1N1)pdm09 out of Mexico by air at the start of the 2009 pandemic. METHODS: Data from flight itineraries for travellers who flew from Mexico were used to estimate the number of international airports where health screening measures would have been needed, and the number of travellers who would have had to be screened, to assess all air travellers who could have transported the H1N1 influenza virus out of Mexico during the initial stages of the 2009 A(H1N1) pandemic. FINDINGS: Exit screening at 36 airports in Mexico, or entry screening of travellers arriving on direct flights from Mexico at 82 airports in 26 other countries, would have resulted in the assessment of all air travellers at risk of transporting A(H1N1)pdm09 out of Mexico at the start of the pandemic. Entry screening of 116 travellers arriving from Mexico by direct or connecting flights would have been necessary for every one traveller at risk of transporting A(H1N1)pdm09. Screening at just eight airports would have resulted in the assessment of 90% of all air travellers at risk of transporting A(H1N1)pdm09 out of Mexico in the early stages of the pandemic. CONCLUSION: During the earliest stages of the A(H1N1) pandemic, most public health benefits potentially attainable through the screening of air travellers could have been achieved by screening travellers at only eight airports.",,"['Khan, Kamran', 'Eckhardt, Rose', 'Brownstein, John S', 'Naqvi, Raza', 'Hu, Wei', 'Kossowsky, David', 'Scales, David', 'Arino, Julien', 'MacDonald, Michael', 'Wang, Jun', 'Sears, Jennifer', 'Cetron, Martin S']",,,,
,PMC,Discovering New Medicines Targeting Helicases: Challenges and Recent Progress,http://dx.doi.org/10.1177/1087057113482586,PMC4427233,,,"Helicases are ubiquitous motor proteins that separate and/or rearrange nucleic acid duplexes in reactions fueled by adenosine triphosphate (ATP) hydrolysis. Helicases encoded by bacteria, viruses, and human cells are widely studied targets for new antiviral, antibiotic, and anticancer drugs. This review summarizes the biochemistry of frequently targeted helicases. These proteins include viral enzymes from herpes simplex virus, papillomaviruses, polyomaviruses, coronaviruses, the hepatitis C virus, and various flaviviruses. Bacterial targets examined include DnaB-like and RecBCD-like helicases. The human DEAD-box protein DDX3 is the cellular antiviral target discussed, and cellular anticancer drug targets discussed are the human RecQ-like helicases and eIF4A. We also review assays used for helicase inhibitor discovery and the most promising and common helicase inhibitor chemotypes, such as nucleotide analogues, polyphenyls, metal ion chelators, flavones, polycyclic aromatic polymers, coumarins, and various DNA binding pharmacophores. Also discussed are common complications encountered while searching for potent helicase inhibitors and possible solutions for these problems.",,"['Shadrick, William R.', 'Ndjomou, Jean', 'Kolli, Rajesh', 'Mukherjee, Sourav', 'Hanson, Alicia M.', 'Frick, David N.']",,,,
,PMC,Vγ9Vδ2-T lymphocytes have impaired antiviral function in small-for-gestational-age and preterm neonates,http://dx.doi.org/10.1038/cmi.2012.78,PMC4012779,,,"Preterm and small-for-gestational-age (SGA) neonates are vulnerable groups that are susceptible to various microbial infections. Vγ9Vδ2-T cells are critical components of the host immune system and have been demonstrated to play an important role in the defense against viral infection in adults. However, the characteristics of Vγ9Vδ2-T cells in children, especially the preterm and SGA populations, are poorly understood. Here, we examined the frequency and antiviral function of Vγ9Vδ2-T cells in neonates, including preterm, SGA and full-term babies. When compared to adults, neonates had a significantly lower percentage of Vγ9Vδ2-T cells in the blood. Upon influenza virus stimulation, neonatal Vγ9Vδ2-T cells, especially from preterm and SGA babies, showed markedly decreased and delayed antiviral cytokine responses than those of adults. In addition, the antiviral responses of neonatal Vγ9Vδ2-T cells were positively correlated with gestational age and birth weight. Finally, a weaker expansion of Vγ9Vδ2-T cells by isopentenyl pyrophosphate (IPP) was shown in neonates than the expansion in adults. Our data suggest that the depressed antiviral activity and decreased frequency of Vγ9Vδ2-T cells may likely account for the high susceptibility to microbial infection in neonates, particularly in preterm and SGA babies. Improving Vγ9Vδ2-T-cell function of neonates may provide a new way to defend against virus infection.",,"['Li, Jinrong', 'Li, Hong', 'Mao, Huawei', 'Yu, Meixing', 'Feng, Ting', 'Yang, Fan', 'Fan, Yingying', 'Lu, Qiao', 'Shen, Chongyang', 'Yin, Zhongwei', 'Tu, Wenwei', 'Mao, Meng']",,,,
,PMC,The role of mutational robustness in RNA virus evolution,http://dx.doi.org/10.1038/nrmicro3003,PMC3981611,,,"RNA viruses face dynamic environments and are masters at adaptation. During their short ‘lifespans’, they must surmount multiple physical, anatomical and immunological challenges. Central to their adaptative capacity is the enormous genetic diversity that characterizes RNA virus populations. Although genetic diversity increases the rate of adaptive evolution, low replication fidelity can present a risk because excess mutations can lead to population extinction. In this Review, we discuss the strategies used by RNA viruses to deal with the increased mutational load and consider how this mutational robustness might influence viral evolution and pathogenesis.",,"['Lauring, Adam S.', 'Frydman, Judith', 'Andino, Raul']",,,,
,PMC,Regulation of the Bone-restricted IFITM-like (Bril) Gene Transcription by Sp and Gli Family Members and CpG Methylation,http://dx.doi.org/10.1074/jbc.M113.457010,PMC3650367,,,"Bril encodes a small membrane protein present in osteoblasts. In humans, a single recurrent mutation in the 5′-UTR of BRIL causes osteogenesis imperfecta type V. The exact function of BRIL and the mechanism by which it contributes to disease are still unknown. The goal of the current study was to characterize the mechanisms governing Bril transcription in humans, rats, and mice. In the three species, as detected by luciferase reporter assays in UMR106 cells, we found that most of the base-line regulatory activity was localized within ∼250 bp upstream of the coding ATG. Co-transfection experiments indicated that Sp1 and Sp3 were potent inducers of the promoter activity, through the binding of several GC-rich boxes. Osterix was a weak activator but acted cooperatively with Sp1 and GLI2 to synergistically induce the BRIL promoter. GLI2, a mediator of hedgehog signaling pathway, was also a potent activator of BRIL through a single GLI binding site. Correspondingly, agonists of the hedgehog pathway (purmorphamine and Indian hedgehog) in MC3T3 osteoblasts led to increased BRIL levels. The BRIL promoter activity was also found to be negatively modulated through two different mechanisms. First, the ZFP354C zinc finger protein repressed basal and Sp1-induced activity. Second, CpG methylation of the promoter region correlated with an inactive state and prevented Sp1 activation. The data provide the very first analyses of the cis- and trans-acting factors regulating Bril transcription. They revealed key roles for the Sp members and GLI2 that possibly cooperate to activate Bril when the promoter becomes demethylated.",,"['Kasaai, Bahar', 'Gaumond, Marie-Hélène', 'Moffatt, Pierre']",,,,
,PMC,Systematic Review of Strategies to Manage and Allocate Scarce Resources during Mass Casualty Events,http://dx.doi.org/10.1016/j.annemergmed.2013.02.005,PMC6997611,,,"CONTEXT: Efficient management and allocation of scarce medical resources can improve outcomes for victims of Mass Casualty Events (MCEs). However, the effectiveness of specific strategies has never been systematically reviewed. OBJECTIVES: We analyzed published evidence on strategies to optimize the management and allocation of scarce resources across a wide range of MCE contexts and study designs. DATA SOURCES: Our literature search included Medline, Scopus, Embase, Cumulative Index to Nursing and Allied Health Literature, Global Health, Web of Science®, and the Cochrane Database of Systematic Reviews, from 1990 through late 2011. We also searched the grey literature using the New York Academy of Medicine’s Grey Literature Report and key websites. We included both English and foreign language articles. STUDY SELECTION: We included studies that evaluated strategies employed in real-world MCEs or tested through drills, exercises, or computer simulations. We excluded studies that lacked a comparison group or did not report quantitative outcomes. DATA EXTRACTION AND SYNTHESIS: Data extraction, quality assessment, and strength of evidence ratings were conducted by a single researcher and reviewed by a second; discrepancies were reconciled by the two reviewers. Due to heterogeneity in outcome measures, we qualitatively synthesized findings within categories of strategies. RESULTS: From 5,716 potentially relevant citations, 74 studies met inclusion criteria. Strategies included: reducing demand for healthcare services (18 studies), optimizing use of existing resources (50), augmenting existing resources (5), implementing crisis standards of care (5), and multiple categories (4). The evidence was sufficient to form conclusions on two strategies, although the strength of evidence was rated as low. First, as a strategy to reduce demand for healthcare services, Points of Dispensing (PODs) can be used to efficiently distribute biological countermeasures following a bioterror attack or influenza pandemic, and their organization influences speed of distribution. Second, as a strategy to optimize use of existing resources, commonly used field triage systems do not perform consistently during actual MCEs. The number of high-quality studies addressing other strategies was insufficient to support conclusions about their effectiveness because of differences in study context, comparison groups, and outcome measures. LIMITATIONS: Our literature search may have missed key resource management and allocation strategies due to their extreme heterogeneity. Inter-rater reliability was not assessed for quality assessments or strength of evidence ratings. Publication bias is likely given the large number of studies reporting positive findings. CONCLUSIONS: The current evidence base is inadequate to inform providers and policymakers about the most effective strategies for managing or allocating scarce resources during MCEs. Consensus on methodological standards that encompass a range of study designs is needed to guide future research and strengthen the evidence base. Evidentiary standards should be developed to promote consensus interpretations of the evidence supporting individual strategies.",,"['Timbie, JW', 'Ringel, JS', 'Fox, DS', 'Pillemer, F', 'Waxman, DA', 'Moore, M', 'Hansen, CK', 'Knebel, A', 'Ricciardi, R', 'Kellermann, AL']",,,,
,PMC,Multiple scales of selection influence the evolutionary emergence of novel pathogens,http://dx.doi.org/10.1098/rstb.2012.0333,PMC3678334,,,"When pathogens encounter a novel environment, such as a new host species or treatment with an antimicrobial drug, their fitness may be reduced so that adaptation is necessary to avoid extinction. Evolutionary emergence is the process by which new pathogen strains arise in response to such selective pressures. Theoretical studies over the last decade have clarified some determinants of emergence risk, but have neglected the influence of fitness on evolutionary rates and have not accounted for the multiple scales at which pathogens must compete successfully. We present a cross-scale theory for evolutionary emergence, which embeds a mechanistic model of within-host selection into a stochastic model for emergence at the population scale. We explore how fitness landscapes at within-host and between-host scales can interact to influence the probability that a pathogen lineage will emerge successfully. Results show that positive correlations between fitnesses across scales can greatly facilitate emergence, while cross-scale conflicts in selection can lead to evolutionary dead ends. The local genotype space of the initial strain of a pathogen can have disproportionate influence on emergence probability. Our cross-scale model represents a step towards integrating laboratory experiments with field surveillance data to create a rational framework to assess emergence risk.",,"['Park, Miran', 'Loverdo, Claude', 'Schreiber, Sebastian J.', 'Lloyd-Smith, James O.']",,,,
,PMC,Simultaneously reconstructing viral cross-species transmission history and identifying the underlying constraints,http://dx.doi.org/10.1098/rstb.2012.0196,PMC3678322,,,"The factors that determine the origin and fate of cross-species transmission events remain unclear for the majority of human pathogens, despite being central for the development of predictive models and assessing the efficacy of prevention strategies. Here, we describe a flexible Bayesian statistical framework to reconstruct virus transmission between different host species based on viral gene sequences, while simultaneously testing and estimating the contribution of several potential predictors of cross-species transmission. Specifically, we use a generalized linear model extension of phylogenetic diffusion to perform Bayesian model averaging over candidate predictors. By further extending this model with branch partitioning, we allow for distinct host transition processes on external and internal branches, thus discriminating between recent cross-species transmissions, many of which are likely to result in dead-end infections, and host shifts that reflect successful onwards transmission in the new host species. Our approach corroborates genetic distance between hosts as a key determinant of both host shifts and cross-species transmissions of rabies virus in North American bats. Furthermore, our results indicate that geographical range overlap is a modest predictor for cross-species transmission, but not for host shifts. Although our evolutionary framework focused on the multi-host reservoir dynamics of bat rabies virus, it is applicable to other pathogens and to other discrete state transition processes.",,"['Faria, Nuno Rodrigues', 'Suchard, Marc A.', 'Rambaut, Andrew', 'Streicker, Daniel G.', 'Lemey, Philippe']",,,,
,PMC,Molecular evolutionary signatures reveal the role of host ecological dynamics in viral disease emergence and spread,http://dx.doi.org/10.1098/rstb.2012.0194,PMC3678321,,,"RNA viruses account for numerous emerging and perennial infectious diseases, and are characterized by rapid rates of molecular evolution. The ecological dynamics of most emerging RNA viruses are still poorly understood and difficult to ascertain. The availability of genome sequence data for many RNA viruses, in principle, could be used to infer ecological dynamics if changes in population numbers produced a lasting signature within the pattern of genome evolution. As a result, the rapidly emerging phylogeographic structure of a pathogen, shaped by the rise and fall in the number of infections and their spatial distribution, could be used as a surrogate for direct ecological assessments. Based on rabies virus as our example, we use a model combining ecological and evolutionary processes to test whether variation in the rate of host movement results in predictive diagnostic patterns of pathogen genetic structure. We identify several linearizable relationships between host dispersal rate and measures of phylogenetic structure suggesting genetic information can be used to directly infer ecological process. We also find phylogenetic structure may be more revealing than demography for certain ecological processes. Our approach extends the reach of current analytic frameworks for infectious disease dynamics by linking phylogeography back to underlying ecological processes.",,"['Duke-Sylvester, Scott M.', 'Biek, Roman', 'Real, Leslie A.']",,,,
,PMC,Evolutionary epidemiology: preparing for an age of genomic plenty,http://dx.doi.org/10.1098/rstb.2012.0193,PMC3678320,,,,,"['Pybus, O. G.', 'Fraser, C.', 'Rambaut, A.']",,,,
,PMC,Crystal structure-based exploration of the important role of Arg106 in the RNA-binding domain of human coronavirus OC43 nucleocapsid protein,http://dx.doi.org/10.1016/j.bbapap.2013.03.003,PMC3774783,,,"Human coronavirus OC43 (HCoV-OC43) is a causative agent of the common cold. The nucleocapsid (N) protein, which is a major structural protein of CoVs, binds to the viral RNA genome to form the virion core and results in the formation of the ribonucleoprotein (RNP) complex. We have solved the crystal structure of the N-terminal domain of HCoV-OC43 N protein (N-NTD) (residues 58 to 195) to a resolution of 2.0Å. The HCoV-OC43 N-NTD is a single domain protein composed of a five-stranded β-sheet core and a long extended loop, similar to that observed in the structures of N-NTDs from other coronaviruses. The positively charged loop of the HCoV-OC43 N-NTD contains a structurally well-conserved positively charged residue, R106. To assess the role of R106 in RNA binding, we undertook a series of site-directed mutagenesis experiments and docking simulations to characterize the interaction between R106 and RNA. The results show that R106 plays an important role in the interaction between the N protein and RNA. In addition, we showed that, in cells transfected with plasmids that encoded the mutant (R106A) N protein and infected with virus, the level of the matrix protein gene was decreased by 7-fold compared to cells that were transfected with the wild-type N protein. This finding suggests that R106, by enhancing binding of the N protein to viral RNA plays a critical role in the viral replication. The results also indicate that the strength of N protein/RNA interactions is critical for HCoV-OC43 replication.",,"['Chen, I-Jung', 'Yuann, Jeu-Ming P.', 'Chang, Yu-Ming', 'Lin, Shing-Yen', 'Zhao, Jincun', 'Perlman, Stanley', 'Shen, Yo-Yu', 'Huang, Tai-Huang', 'Hou, Ming-Hon']",,,,
,PMC,"Accurate SHAPE-directed RNA secondary structure modeling, including pseudoknots",http://dx.doi.org/10.1073/pnas.1219988110,PMC3619282,,,"A pseudoknot forms in an RNA when nucleotides in a loop pair with a region outside the helices that close the loop. Pseudoknots occur relatively rarely in RNA but are highly overrepresented in functionally critical motifs in large catalytic RNAs, in riboswitches, and in regulatory elements of viruses. Pseudoknots are usually excluded from RNA structure prediction algorithms. When included, these pairings are difficult to model accurately, especially in large RNAs, because allowing this structure dramatically increases the number of possible incorrect folds and because it is difficult to search the fold space for an optimal structure. We have developed a concise secondary structure modeling approach that combines SHAPE (selective 2′-hydroxyl acylation analyzed by primer extension) experimental chemical probing information and a simple, but robust, energy model for the entropic cost of single pseudoknot formation. Structures are predicted with iterative refinement, using a dynamic programming algorithm. This melded experimental and thermodynamic energy function predicted the secondary structures and the pseudoknots for a set of 21 challenging RNAs of known structure ranging in size from 34 to 530 nt. On average, 93% of known base pairs were predicted, and all pseudoknots in well-folded RNAs were identified.",,"['Hajdin, Christine E.', 'Bellaousov, Stanislav', 'Huggins, Wayne', 'Leonard, Christopher W.', 'Mathews, David H.', 'Weeks, Kevin M.']",,,,
,PMC,Physiological difference in autophagic flux in macrophages from two mouse strains regulates cholesterol ester metabolism,http://dx.doi.org/10.1161/ATVBAHA.112.301041,PMC3646371,,,"OBJECTIVE: DBA/2 apoE−/− mice have ~10-fold larger lesions than AKR apoE−/− mice. The objective of this study was to determine if macrophages from these two strains had altered cholesterol metabolism that might play a role in their divergent atherosclerosis susceptibility. APPROACH AND RESULTS: AKR and DBA/2 macrophages incubated with acetylated LDL (AcLDL) resulted in higher cholesterol ester (CE) and lower free cholesterol (FC) accumulation in the DBA/2 cells. However, these strains had equivalent AcLDL uptake and cholesterol esterification activity. Cholesterol efflux from unloaded cells to apoAI or HDL was similar in the two strains. However, upon AcLDL loading, cholesterol efflux was impaired in the DBA/2 cells, but this impairment was corrected by loading in the presence of an inhibitor of cholesterol esterification. Thus, the cholesterol efflux capabilities are similar in these strains, but there appeared to be a defect in lipid droplet (LD)-stored CE mobilization in DBA/2 cells. Lalistat-1, a specific inhibitor of lysosomal acid lipase, completely blocked the hydrolysis of LD-stored CE, implying that LD autophagy is responsible for CE turnover in these cells. CE turnover was 2-fold slower in DBA/2 vs. AKR cells. Autophagic flux, estimated by a fluorescent LC3-II reporter and the increase in p62 levels after chloroquine treatment, was higher in AKR vs. DBA/2 macrophages, which had an apparent decrease in autophagosome fusion with lysosomes. When autophagy was activated by amino acid starvation, CE levels decreased in DBA/2 cells. CONCLUSIONS: Physiological regulation of autophagy in macrophages controls CE accumulation and may modify atherosclerosis susceptibility.",,"['Robinet, Peggy', 'Ritchey, Brian', 'Smith, Jonathan D.']",,,,
,PMC,Health Systems’ “Surge Capacity”: State of the Art and Priorities for Future Research,http://dx.doi.org/10.1111/milq.12003,PMC3607127,,,"CONTEXT: Over the past decade, a number of high-impact natural hazard events, together with the increased recognition of pandemic risks, have intensified interest in health systems’ ability to prepare for, and cope with, “surges” (sudden large-scale escalations) in treatment needs. In this article, we identify key concepts and components associated with this emerging research theme. We consider the requirements for a standardized conceptual framework for future research capable of informing policy to reduce the morbidity and mortality impacts of such incidents. Here our objective is to appraise the consistency and utility of existing conceptualizations of health systems’ surge capacity and their components, with a view to standardizing concepts and measurements to enable future research to generate a cumulative knowledge base for policy and practice. METHODS: A systematic review of the literature on concepts of health systems’ surge capacity, with a narrative summary of key concepts relevant to public health. FINDINGS: The academic literature on surge capacity demonstrates considerable variation in its conceptualization, terms, definitions, and applications. This, together with an absence of detailed and comparable data, has hampered efforts to develop standardized conceptual models, measurements, and metrics. Some degree of consensus is evident for the components of surge capacity, but more work is needed to integrate them. The overwhelming concentration in the United States complicates the generalizability of existing approaches and findings. CONCLUSIONS: The concept of surge capacity is a useful addition to the study of health systems’ disaster and/or pandemic planning, mitigation, and response, and it has far-reaching policy implications. Even though research in this area has grown quickly, it has yet to fulfill its potential to generate knowledge to inform policy. Work is needed to generate robust conceptual and analytical frameworks, along with innovations in data collection and methodological approaches that enhance health systems’ readiness for, and response to, unpredictable high-consequence surges in demand.",,"['Watson, Samantha K', 'Rudge, James W', 'Coker, Richard']",,,,
,PMC,Canine and Feline Parvoviruses Preferentially Recognize the Non-Human Cell Surface Sialic Acid N-glycolylneuraminic acid,http://dx.doi.org/10.1016/j.virol.2013.02.009,PMC3634669,,,"Feline panleukopenia virus (FPV) is a pathogen whose canine-adapted form (canine parvovirus (CPV)) emerged in 1978. These viruses infect by binding host transferrin receptor type-1 (TfR), but also hemagglutinate erythrocytes. We show that hemagglutination involves selective recognition of the non-human sialic acid N-glycolylneuraminic acid (Neu5Gc) but not N-acetylneuraminic acid (Neu5Ac), which differs by only one oxygen atom from Neu5Gc. Overexpression of α2-6 sialyltransferase did not change binding, indicating that both α2-3 and α2-6 linkages are recognized. However, Neu5Gc expression on target cells did not enhance CPV or FPV infection in vitro. Thus, the conserved Neu5Gc-binding preference of these viruses likely plays a role in the natural history of the virus in vivo. Further studies must clarify relationships between virus infection and host Neu5Gc expression. As a first step, we show that transcripts of CMAH (which generates Neu5Gc from Neu5Ac) are at very low levels in Western dog breed cells.",,"['Löfling, Jonas', 'Lyi, Sangbom Michael', 'Parrish, Colin R.', 'Varki, Ajit']",,,,
,PMC,MOVING H5N1 STUDIES INTO THE ERA OF SYSTEMS BIOLOGY,http://dx.doi.org/10.1016/j.virusres.2013.02.011,PMC3834220,,,"The dynamics of H5N1 influenza virus pathogenesis are multifaceted and can be seen as an emergent property that cannot be comprehended without looking at the system as a whole. In past years, most of the high-throughput studies on H5N1-host interactions have focused on the host transcriptomic response, at the cellular or the lung tissue level. These studies pointed out that the dynamics and magnitude of the innate immune response and immune cell infiltration is critical to H5N1 pathogenesis. However, viral-host interactions are multidimensional and advances in technologies are creating new possibilities to systematically measure additional levels of ‘omic data (e.g. proteomic, metabolomic, and RNA profiling) at each temporal and spatial scale (from the single cell to the organism) of the host response. Natural host genetic variation represents another dimension of the host response that determines pathogenesis. Systems biology models of H5N1 disease aim at understanding and predicting pathogenesis through integration of these different dimensions by using intensive computational modeling. In this review, we describe the importance of ‘omic studies for providing a more comprehensive view of infection and mathematical models that are being developed to integrate these data. This review provides a roadmap for what needs to be done in the future and what computational strategies should be used to build a global model of H5N1 pathogenesis. It is time for systems biology of H5N1 pathogenesis to take center stage as the field moves towards a more comprehensive view of virus-host interactions.",,"['Josset, Laurence', 'Go, Jennifer Tisoncik', 'Katze, Michael G.']",,,,
,PMC,Inhibition of DD-Peptidases by a Specific Trifluoroketone: Crystal Structure of a Complex with the Actinomadura R39 DD-Peptidase(),http://dx.doi.org/10.1021/bi400048s,PMC3731424,,,"Inhibitors of bacterial DD-peptidases represent potential antibiotics. In the search for alternatives to β-lactams, we have investigated a series of compounds designed to generate transition state analogue structures on reaction with DD-peptidases. The compounds contain a combination of a peptidoglycan-mimetic specificity handle and a warhead capable of delivering a tetrahedral anion to the enzyme active site. The latter include a boronic acid, two alcohols, an aldehyde and a trifluoroketone. The compounds were tested against two low molecular mass class C DD-peptidases. As expected from previous observations, the boronic acid was a potent inhibitor, but, rather unexpectedly from precedent, the trifluoroketone [D-α-aminopimelyl-(1,1,1-trifluoro-3-amino)butan-2-one] was also very effective. Taking into account competing hydration, the trifluoroketone was the strongest inhibitor of the Actinomadura R39 DD-peptidase, with a subnanomolar (free ketone) inhibition constant. A crystal structure of the complex between the trifluoroketone and the R39 enzyme showed that a tetrahedral adduct had indeed formed with the active site serine nucleophile. The trifluoroketone moiety, therefore, should be considered along with boronic acids and phosphonates, as a warhead that can be incorporated into new and effective DD-peptidase inhibitors and therefore, perhaps, antibiotics.",,"['Dzhekieva, Liudmila', 'Adediran, S. A.', 'Herman, Raphael', 'Kerff, Frédéric', 'Duez, Colette', 'Charlier, Paulette', 'Sauvage, Eric', 'Pratt, R.F.']",,,,
,PMC,The genetic code as expressed through relationships between mRNA structure and protein function,http://dx.doi.org/10.1016/j.febslet.2013.03.002,PMC4269304,,,"Structured RNA elements within messenger RNA often direct or modulate the cellular production of active proteins. As reviewed here, RNA structures have been discovered that govern nearly every step in protein production: mRNA production and stability; translation initiation, elongation, and termination; protein folding; and cellular localization. Regulatory RNA elements are common within RNAs from every domain of life. This growing body of RNA-mediated mechanisms continues to reveal new ways in which mRNA structure regulates translation. We integrate examples from several different classes of RNA structure-mediated regulation to present a global perspective that suggests that the secondary and tertiary structure of RNA ultimately constitutes an additional level of the genetic code that both guides and regulates protein biosynthesis.",,"['Mauger, David M.', 'Siegfried, Nathan A.', 'Weeks, Kevin M.']",,,,
,PMC,Traffic COPs: rules of detection,http://dx.doi.org/10.1038/emboj.2013.57,PMC3616295,,,"EMBO J (2013) 32:11, 926–937 doi:10.1038/emboj.2013.41; published online 03122013 Dev Cell (2012) 23: 1255–62 doi:10.1016/j.devcel.2012.10.017; published online 12112012 How specific cargo recognition by coat proteins is achieved and how this recognition event may regulate vesicle formation are still under investigation. In two recent papers by the Owen and Goldberg labs, the binding mode of dilysine motifs to the coatomer of the COPI coat has been analysed. Collectively, their findings suggest that the dilysine motif containing cargo proteins may stabilize coat complexes on membranes and enhance the chance for coat polymerization and vesicle budding.",,"Spang, Anne",,,,
,PMC,Rules for the recognition of dilysine retrieval motifs by coatomer,http://dx.doi.org/10.1038/emboj.2013.41,PMC3616288,,,"Cytoplasmic dilysine motifs on transmembrane proteins are captured by coatomer α-COP and β′-COP subunits and packaged into COPI-coated vesicles for Golgi-to-ER retrieval. Numerous ER/Golgi proteins contain K(x)Kxx motifs, but the rules for their recognition are unclear. We present crystal structures of α-COP and β′-COP bound to a series of naturally occurring retrieval motifs—encompassing KKxx, KxKxx and non-canonical RKxx and viral KxHxx sequences. Binding experiments show that α-COP and β′-COP have generally the same specificity for KKxx and KxKxx, but only β′-COP recognizes the RKxx signal. Dilysine motif recognition involves lysine side-chain interactions with two acidic patches. Surprisingly, however, KKxx and KxKxx motifs bind differently, with their lysine residues transposed at the binding patches. We derive rules for retrieval motif recognition from key structural features: the reversed binding modes, the recognition of the C-terminal carboxylate group which enforces lysine positional context, and the tolerance of the acidic patches for non-lysine residues.",,"['Ma, Wenfu', 'Goldberg, Jonathan']",,,,
,PMC,Intracellular RNA recognition pathway activates strong anti-viral response in human mast cells,http://dx.doi.org/10.1111/cei.12042,PMC3719938,,,"Mast cells have been implicated in the first line of defence against parasites and bacteria, but less is known about their role in anti-viral responses. Allergic diseases often exacerbate during viral infection, suggesting an increased activation of mast cells in the process. In this study we investigated human mast cell response to double-stranded RNA and viral infection. Cultured human mast cells were incubated with poly(I:C), a synthetic RNA analogue and live Sendai virus as a model of RNA parainfluenza virus infection, and analysed for their anti-viral response. Mast cells responded to intracellular poly(I:C) by inducing type 1 and type 3 interferons and TNF-α. In contrast, extracellular Toll-like receptor 3 (TLR)-3-activating poly(I:C) failed to induce such response. Infection of mast cells with live Sendai virus induced an anti-viral response similar to that of intracellular poly(I:C). Type 1, but not type 3 interferons, up-regulated the expression of melanoma differentiation–associated gene 5 (MDA-5) and retinoic acid-inducible gene-1 (RIG-1), and TLR-3, demonstrating that human mast cells do not express functional receptors for type 3 interferons. Furthermore, virus infection induced the anti-viral proteins MxA and IFIT3 in human mast cells. In conclusion, our results support the notion that mast cells can recognize an invading virus through intracellular virus sensors and produce high amounts of type 1 and type 3 interferons and the anti-viral proteins human myxovirus resistance gene A (MxA) and interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in response to the virus infection.",,"['Lappalainen, J', 'Rintahaka, J', 'Kovanen, P T', 'Matikainen, S', 'Eklund, K K']",,,,
,PMC,A New Helicase Assay Based on Graphene Oxide for Anti-Viral Drug Development,http://dx.doi.org/10.1007/s10059-013-0066-1,PMC3887892,,,"Recently, graphene oxide (GO), one of the carbon nanomaterials, has received much attention due to its unique physical and chemical properties and high potential in many research areas, including applications as a biosensor and drug delivery vehicle. Various GO-based biosensors have been developed, largely based on its surface adsorption properties for detecting biomolecules, such as nucleotides and peptides, and real-time monitoring of enzymatic reactions. In this review, we discuss recent advances in GO-based biosensors focusing on a novel assay platform for helicase activity, which was also employed in high-throughput screening to discover selective helicase inhibitors.",,"['Jang, Hongje', 'Ryoo, Soo-Ryoon', 'Lee, Min Jae', 'Han, Sang Woo', 'Min, Dal-Hee']",,,,
,PMC,Synthesis and Immunological Evaluation of a MUC1 Glycopeptide Incorporated into l-Rhamnose Displaying Liposomes,http://dx.doi.org/10.1021/bc300422a,PMC3623543,,,"MUC1 variable number tandem repeats (VNTRs) conjugated to tumor-associated carbohydrate antigens (TACAs) have been shown to break self-tolerance in humanized MUC1 transgenic mice. Therefore, we hypothesize that a MUC1 VNTR TACA-conjugate can be successfully formulated into a liposome-based anti-cancer vaccine. The immunogenicity of the vaccine should be further augmented by incorporating surface displayed L-rhamnose (Rha) epitopes onto the liposomes to take advantage of a natural antibody-dependent antigen uptake mechanism. To validate our hypothesis we synthesized a 20-amino acid MUC1 glycopeptide containing a GalNAc-O-Thr (Tn) TACA by SPPS and conjugated it to a functionalized Toll-like receptor ligand (TLRL). An L-Rha-cholesterol conjugate was prepared using tetraethylene glycol (TEG) as a linker. The liposome-based anti-cancer vaccine was formulated by the extrusion method using TLRL-MUC1-Tn conjugate, Rha-TEG-cholesterol and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) in a total lipid concentration of 30 mM. The stability, homogeneity and size characterization of the liposomes was evaluated by SEM and DLS measurements. The formulated liposomes demonstrated positive binding with both anti-Rha and mouse anti-human MUC1 antibodies. Groups of female BALB/c mice were immunized and boosted with a rhamnose-Ficoll (Rha-Ficoll) conjugate formulated with alum as adjuvant to generate the appropriate concentration of anti-Rha antibodies in the mice. Anti-Rha antibody titers were >25-fold higher in the groups of mice immunized with the Rha-Ficoll conjugate than the non-immunized control groups. The mice were then immunized with the TLRL-MUC1-Tn liposomal vaccine formulated either with or without the surface displaying Rha epitopes. Sera collected from the groups of mice initially immunized with Rha-Ficoll and later vaccinated with the Rha-displaying TLRL-MUC1-Tn liposomes showed a >8-fold increase in both anti-MUC1-Tn and anti-Tn antibody titers in comparison to the groups of mice that did not receive Rha-Ficoll. T-cells from BALB/c mice primed with a MUC1-Tn peptide demonstrated increased proliferation to the Rha-liposomal vaccine in the presence of antibodies isolated from Rha-Ficoll immunized mice compared to nonimmune mice, supporting the proposed effect on antigen presentation. The anti-MUC1-Tn antibodies in the vaccinated mice serum recognized MUC1 on human leukemia U266 cells. Because this vaccine uses separate rhamnose and antigenic epitope components, the vaccine can easily be targeted to different antigens or epitopes by changing the peptide without having to change the other components.",,"['Sarkar, Sourav', 'Salyer, Alex C. D.', 'Wall, Katherine A.', 'Sucheck, Steven J.']",,,,
,PMC,Novel vaccine strategies against emerging viruses,http://dx.doi.org/10.1016/j.coviro.2013.02.001,PMC3644304,,,"One of the main public health concerns of emerging viruses is their potential introduction into and sustained circulation among populations of immunologically naïve, susceptible hosts. The induction of protective immunity through vaccination can be a powerful tool to prevent this concern by conferring protection to the population at risk. Conventional approaches to develop vaccines against emerging pathogens have significant limitations: lack of experimental tools for several emerging viruses of concern, poor immunogenicity, safety issues, or lack of cross-protection against antigenic variants. The unpredictability of the emergence of future virus threats demands the capability to rapidly develop safe, effective vaccines. We describe some recent advances in new vaccine strategies that are being explored as alternatives to classical attenuated and inactivated vaccines, and provide examples of potential novel vaccines for emerging viruses. These approaches might be applied to the control of many other emerging pathogens.",,"['García-Sastre, Adolfo', 'Mena, Ignacio']",,,,
,PMC,STING Recognition of Cytoplasmic DNA Instigates Cellular Defense,http://dx.doi.org/10.1016/j.molcel.2013.01.039,PMC3881179,,,"How the cell recognizes cytosolic DNA including DNA based microbes to trigger host defense related gene activation remains to be fully resolved. Here, we demonstrate that STING (for Stimulator of Interferon Genes), an endoplasmic reticulum (ER) translocon associated transmembrane protein, acts to detect cytoplasmic DNA species. STING homodimers were able to complex with self (apoptotic, necrotic) or pathogen related ssDNA and dsDNA and were indispensible for HSV-1-mediated transcriptional activation of a wide array of innate immune and pro-inflammatory genes in addition to type I IFN. Our data indicates that STING instigates cytoplasmic DNA-mediated cellular defense gene transcription and facilitates adoptive responses that are required for protection of the host. In contrast, chronic STING activation may manifest inflammatory responses and possibly autoimmune disease triggered by self-DNA.",,"['Abe, Takayuki', 'Harashima, Ai', 'Xia, Tianli', 'Konno, Hiroyasu', 'Konno, Keiko', 'Morales, Alejo', 'Ahn, Jeonghyun', 'Gutman, Delia', 'Barber, Glen N.']",,,,
,PMC,Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease(1)(2)(3),http://dx.doi.org/10.3945/an.112.003210,PMC3649098,,,"The essentiality of zinc in humans was established in 1963. During the past 50 y, tremendous advances in both clinical and basic sciences of zinc metabolism in humans have been observed. The major factor contributing to zinc deficiency is high phytate-containing cereal protein intake in the developing world, and nearly 2 billion subjects may be zinc deficient. Conditioned deficiency of zinc has been observed in patients with malabsorption syndrome, liver disease, chronic renal disease, sickle cell disease, and other chronic illnesses. Major clinical problems resulting from zinc deficiency in humans include growth retardation; cell-mediated immune dysfunction, and cognitive impairment. In the Middle East, zinc-deficient dwarfs did not live beyond the age of 25 y, and they died because of intercurrent infections. In 1963, we knew of only 3 enzymes that required zinc for their activities, but now we know of >300 enzymes and >1000 transcription factors that are known to require zinc for their activities. Zinc is a second messenger of immune cells, and intracellular free zinc in these cells participate in signaling events. Zinc has been very successfully used as a therapeutic modality for the management of acute diarrhea in children, Wilson’s disease, the common cold and for the prevention of blindness in patients with age-related dry type of macular degeneration and is very effective in decreasing the incidence of infection in the elderly. Zinc not only modulates cell-mediated immunity but is also an antioxidant and anti-inflammatory agent.",,"Prasad, Ananda S.",,,,
,PMC,Antigen-specific memory T(reg) control memory responses to influenza virus infection,http://dx.doi.org/10.4049/jimmunol.1203140,PMC3608733,,,"Regulatory CD4(+)FoxP3(+) T cells (Treg) are key regulators of inflammatory responses and control the magnitude of cellular immune responses to viral infections. However, little is known about how Treg contribute to immune regulation during memory responses to previously-encountered pathogens. Here we utilized influenza NP(311-325)/IA(b) Class II tetramers to track the antigen-specific Treg response to primary and secondary influenza virus infections. During secondary infections, antigen-specific memory Treg showed accelerated accumulation in the lung-draining lymph node and lung parenchyma relative to a primary infection. Memory Treg effectively controlled the in vitro proliferation of memory CD8(+) cells in an antigen-specific fashion that was MHC class II dependent. When memory Treg were depleted prior to secondary infection, the magnitude of the antigen-specific memory CD8(+) T cell response was increased, as was pulmonary inflammation and airway cytokine/chemokine expression. Replacement of memory Treg with naïve Treg failed to restore the regulation of the memory CD8 T cell response during secondary infection. Together, these data demonstrate the existence of a previously undescribed population of antigen-specific memory Treg that shape the cellular immune response to secondary influenza virus challenges and offer an additional parameter to consider when determining the efficacy of vaccinations.",,"['Brincks, Erik L.', 'Roberts, Alan D.', 'Cookenham, Tres', 'Sell, Stewart', 'Kohlmeier, Jacob E.', 'Blackman, Marcia A.', 'Woodland, David L.']",,,,
,PMC,Nanoscale assemblies and their biomedical applications,http://dx.doi.org/10.1098/rsif.2012.0740,PMC3565727,,,"Nanoscale assemblies are a unique class of materials, which can be synthesized from inorganic, polymeric or biological building blocks. The multitude of applications of this class of materials ranges from solar and electrical to uses in food, cosmetics and medicine. In this review, we initially highlight characteristic features of polymeric nanoscale assemblies as well as those built from biological units (lipids, nucleic acids and proteins). We give special consideration to protein nanoassemblies found in nature such as ferritin protein cages, bacterial microcompartments and vaults found in eukaryotic cells and designed protein nanoassemblies, such as peptide nanofibres and peptide nanotubes. Next, we focus on biomedical applications of these nanoscale assemblies, such as cell targeting, drug delivery, bioimaging and vaccine development. In the vaccine development section, we report in more detail the use of virus-like particles and self-assembling polypeptide nanoparticles as new vaccine delivery platforms.",,"['Doll, Tais A. P. F.', 'Raman, Senthilkumar', 'Dey, Raja', 'Burkhard, Peter']",,,,
,PMC,Cross-neutralizing activity of human anti-V3 monoclonal antibodies derived from non-B clade HIV-1 infected individuals,http://dx.doi.org/10.1016/j.virol.2012.12.010,PMC3756680,,,"One approach to the development of an HIV vaccine is to design a protein template which can present gp120 epitopes inducing cross-neutralizing antibodies. To select a V3 sequence for immunogen design, we compared the neutralizing activities of 18 anti-V3 monoclonal antibodies (mAbs) derived from Cameroonian and Indian individuals infected with clade AG and C, respectively. It was found that V3 mAbs from the Cameroonian patients were significantly more cross-neutralizing than those from India. Interestingly, superior neutralizing activity of Cameroonian mAbs was also observed among the nine VH5-51/VL lambda genes encoding V3 mAbs which mediate a similar mode of recognition. This correlated with higher relative binding affinity to a variety of gp120s and increased mutation rates in V3 mAbs from Cameroon. These results suggest that clade C V3 is probably weakly immunogenic and that the V3 sequence of CRF02_AG viruses can serve as a plausible template for vaccine immunogen design.",,"['Andrabi, Raiees', 'Williams, Constance', 'Wang, Xiao-Hong', 'Li, Liuzhe', 'Choudhary, Alok K.', 'Wig, Naveet', 'Biswas, Ashutosh', 'Luthra, Kalpana', 'Nadas, Arthur', 'Seaman, Michael S.', 'Nyambi, Phillipe', 'Zolla-Pazner, Susan', 'Gorny, Miroslaw K.']",,,,
,PMC,A mass weighted chemical elastic network model elucidates closed form domain motions in proteins,http://dx.doi.org/10.1002/pro.2244,PMC3649262,,,"An elastic network model (ENM), usually Cα coarse-grained one, has been widely used to study protein dynamics as an alternative to classical molecular dynamics simulation. This simple approach dramatically saves the computational cost, but sometimes fails to describe a feasible conformational change due to unrealistically excessive spring connections. To overcome this limitation, we propose a mass-weighted chemical elastic network model (MWCENM) in which the total mass of each residue is assumed to be concentrated on the representative alpha carbon atom and various stiffness values are precisely assigned according to the types of chemical interactions. We test MWCENM on several well-known proteins of which both closed and open conformations are available as well as three α-helix rich proteins. Their normal mode analysis reveals that MWCENM not only generates more plausible conformational changes, especially for closed forms of proteins, but also preserves protein secondary structures thus distinguishing MWCENM from traditional ENMs. In addition, MWCENM also reduces computational burden by using a more sparse stiffness matrix.",,"['Kim, Min Hyeok', 'Seo, Sangjae', 'Jeong, Jay Il', 'Kim, Bum Joon', 'Liu, Wing Kam', 'Lim, Byeong Soo', 'Choi, Jae Boong', 'Kim, Moon Ki']",,,,
,PMC,Infection Fatality Risk of the Pandemic A(H1N1)2009 Virus in Hong Kong,http://dx.doi.org/10.1093/aje/kws314,PMC3658096,,,"One measure of the severity of a pandemic influenza outbreak at the individual level is the risk of death among people infected by the new virus. However, there are complications in estimating both the numerator and denominator. Regarding the numerator, statistical estimates of the excess deaths associated with influenza virus infections tend to exceed the number of deaths associated with laboratory-confirmed infection. Regarding the denominator, few infections are laboratory confirmed, while differences in case definitions and approaches to case ascertainment can lead to wide variation in case fatality risk estimates. Serological surveillance can be used to estimate the cumulative incidence of infection as a denominator that is more comparable across studies. We estimated that the first wave of the influenza A(H1N1)pdm09 virus in 2009 was associated with approximately 232 (95% confidence interval: 136, 328) excess deaths of all ages in Hong Kong, mainly among the elderly. The point estimates of the risk of death on a per-infection basis increased substantially with age, from below 1 per 100,000 infections in children to 1,099 per 100,000 infections in those 60–69 years of age. Substantial variation in the age-specific infection fatality risk complicates comparison of the severity of different influenza strains.",,"['Wong, Jessica Y.', 'Wu, Peng', 'Nishiura, Hiroshi', 'Goldstein, Edward', 'Lau, Eric H. Y.', 'Yang, Lin', 'Chuang, S. K.', 'Tsang, Thomas', 'Peiris, J. S. Malik', 'Wu, Joseph T.', 'Cowling, Benjamin J.']",,,,
,PMC,Influenza matrix protein 2 alters CFTR expression and function through its ion channel activity,http://dx.doi.org/10.1152/ajplung.00314.2012,PMC3652020,,,"The human cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-activated chloride (Cl(−)) channel in the lung epithelium that helps regulate the thickness and composition of the lung epithelial lining fluid. We investigated whether influenza M2 protein, a pH-activated proton (H(+)) channel that traffics to the plasma membrane of infected cells, altered CFTR expression and function. M2 decreased CFTR activity in 1) Xenopus oocytes injected with human CFTR, 2) epithelial cells (HEK-293) stably transfected with CFTR, and 3) human bronchial epithelial cells (16HBE14o−) expressing native CFTR. This inhibition was partially reversed by an inhibitor of the ubiquitin-activating enzyme E1. Next we investigated whether the M2 inhibition of CFTR activity was due to an increase of secretory organelle pH by M2. Incubation of Xenopus oocytes expressing CFTR with ammonium chloride or concanamycin A, two agents that alkalinize the secretory pathway, inhibited CFTR activity in a dose-dependent manner. Treatment of M2- and CFTR-expressing oocytes with the M2 ion channel inhibitor amantadine prevented the loss in CFTR expression and activity; in addition, M2 mutants, lacking the ability to transport H(+), did not alter CFTR activity in Xenopus oocytes and HEK cells. Expression of an M2 mutant retained in the endoplasmic reticulum also failed to alter CFTR activity. In summary, our data show that M2 decreases CFTR activity by increasing secretory organelle pH, which targets CFTR for destruction by the ubiquitin system. Alteration of CFTR activity has important consequences for fluid regulation and may potentially modify the immune response to viral infection.",,"['Londino, James D.', 'Lazrak, Ahmed', 'Jurkuvenaite, Asta', 'Collawn, James F.', 'Noah, James W.', 'Matalon, Sadis']",,,,
,PMC,Estimation with Right-Censored Observations Under A Semi-Markov Model,http://dx.doi.org/10.1002/cjs.11176,PMC3713855,,,"The semi-Markov process often provides a better framework than the classical Markov process for the analysis of events with multiple states. The purpose of this paper is twofold. First, we show that in the presence of right censoring, when the right end-point of the support of the censoring time is strictly less than the right end-point of the support of the semi-Markov kernel, the transition probability of the semi-Markov process is nonidentifiable, and the estimators proposed in the literature are inconsistent in general. We derive the set of all attainable values for the transition probability based on the censored data, and we propose a nonparametric inference procedure for the transition probability using this set. Second, the conventional approach to constructing confidence bands is not applicable for the semi-Markov kernel and the sojourn time distribution. We propose new perturbation resampling methods to construct these confidence bands. Different weights and transformations are explored in the construction. We use simulation to examine our proposals and illustrate them with hospitalization data from a recent cancer survivor study.",,"['Zhao, Lihui', 'Hu, X. Joan']",,,,
,PMC,Public Health Watch,http://dx.doi.org/10.1177/1715163513482711,PMC3676203,,,,,"Lynas, Kathie",,,,
,PMC,The Altered Gut Microbiome and Necrotizing Enterocolitis,http://dx.doi.org/10.1016/j.clp.2012.12.009,PMC3589666,,,,,"['Torrazza, Roberto Murgas', 'Neu, Josef']",,,,
,PMC,CD4(+) T-cell subsets and host defense in the lung,http://dx.doi.org/10.1111/imr.12030,PMC3576701,,,"CD4(+) T-helper subsets are lineages of T cells that have effector function in the lung and control critical aspects of lung immunity. Depletion of these cells experimentally or by drugs or human immunodeficiency virus (HIV) infection in humans leads to the development of opportunistic infections as well as increased rates of bacteremia with certain bacterial pneumonias. Recently, it has been proposed that CD4(+) T-cell subsets may also be excellent targets for mucosal vaccination to prevent pulmonary infections in susceptible hosts. Here we review recent findings that increase our understanding of T-cell subsets and their effector cytokines in the context of pulmonary infection.",,"Kolls, Jay K.",,,,
,PMC,Esoteric infections and anaesthesiologist: Need for self protection,http://dx.doi.org/10.4103/0019-5049.111832,PMC3696255,23825807,CC BY-NC-SA,,2013 Mar-Apr,"Bhaskar, S Bala",Indian J Anaesth,,,
,PMC,Effects of Spectral Transmittance through Standard Laboratory Cages on Circadian Metabolism and Physiology in Nude Rats,,PMC3624782,,,"Light is potent in circadian, neuroendocrine, and neurobehavioral regulation, thereby having profound influence on the health and wellbeing of all mammals, including laboratory animals. We hypothesized that the spectral quality of light transmitted through colored compared with clear standard rodent cages alters circadian production of melatonin and temporal coordination of normal metabolic and physiologic activities. Female nude rats (Hsd:RH-Foxn1(rnu); n = 6 per group) were maintained on a 12:12-h light:dark regimen (300 lx; lights on, 0600) in standard translucent clear, amber, or blue rodent cages; intensity and duration of lighting were identical for all groups. Rats were assessed for arterial blood levels of pO(2) and pCO(2), melatonin, total fatty acid, glucose, lactic acid, insulin, leptin, and corticosterone concentrations at 6 circadian time points. Normal circadian rhythms of arterial blood pO(2) and pCO(2) were different in rats housed in cages that were blue compared with amber or clear. Plasma melatonin levels (mean ± 1 SD) were low (1.0 ± 0.2 pg/mL) during the light phase in all groups but higher at nighttime in rats in blue cages (928.2 ± 39.5 pg/mL) compared with amber (256.8 ± 6.6 pg/mL) and clear (154.8 ± 9.3 pg/mL) cages. Plasma daily rhythms of total fatty acid, glucose, lactic acid, leptin, insulin, and corticosterone were disrupted in rats housed in blue or amber compared with clear cages. Temporal coordination of circadian rhythms of physiology and metabolism can be altered markedly by changes in the spectral quality of light transmitted through colored standard rodent cages.",,"['Dauchy, Robert T', 'Dauchy, Erin M', 'Hanifin, John P', 'Gauthreaux, Sheena L', 'Mao, Lulu', 'Belancio, Victoria P', 'Ooms, Tara G', 'Dupepe, Lynell M', 'Jablonski, Michael R', 'Warfield, Benjamin', 'Wren, Melissa A', 'Brainard, George C', 'Hill, Steven M', 'Blask, David E']",,,,
,PMC,PCR Followed by Electrospray Ionization Mass Spectrometry for Broad-Range Identification of Fungal Pathogens,http://dx.doi.org/10.1128/JCM.02621-12,PMC3592073,,,"Invasive fungal infections are a significant cause of morbidity and mortality among immunocompromised patients. Early and accurate identification of these pathogens is central to direct therapy and to improve overall outcome. PCR coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) was evaluated as a novel means for identification of fungal pathogens. Using a database grounded by 60 ATCC reference strains, a total of 394 clinical fungal isolates (264 molds and 130 yeasts) were analyzed by PCR/ESI-MS; results were compared to phenotypic identification, and discrepant results were sequence confirmed. PCR/ESI-MS identified 81.4% of molds to either the genus or species level, with concordance rates of 89.7% and 87.4%, respectively, to phenotypic identification. Likewise, PCR/ESI-MS was able to identify 98.4% of yeasts to either the genus or species level, agreeing with 100% of phenotypic results at both the genus and species level. PCR/ESI-MS performed best with Aspergillus and Candida isolates, generating species-level identification in 94.4% and 99.2% of isolates, respectively. PCR/ESI-MS is a promising new technology for broad-range detection and identification of medically important fungal pathogens that cause invasive mycoses.",,"['Massire, Christian', 'Buelow, Daelynn R.', 'Zhang, Sean X.', 'Lovari, Robert', 'Matthews, Heather E.', 'Toleno, Donna M.', 'Ranken, Raymond R.', 'Hall, Thomas A.', 'Metzgar, David', 'Sampath, Rangarajan', 'Blyn, Lawrence B.', 'Ecker, David J.', 'Gu, Zhengming', 'Walsh, Thomas J.', 'Hayden, Randall T.']",,,,
,PMC,Pathogen Chip for Respiratory Tract Infections,http://dx.doi.org/10.1128/JCM.02317-12,PMC3592061,,,"Determining the viral etiology of respiratory tract infections (RTI) has been limited for the most part to specific primer PCR-based methods due to their increased sensitivity and specificity compared to other methods, such as tissue culture. However, specific primer approaches have limited the ability to fully understand the diversity of infecting pathogens. A pathogen chip system (PathChip), developed at the Genome Institute of Singapore (GIS), using a random-tagged PCR coupled to a chip with over 170,000 probes, has the potential to recognize all known human viral pathogens. We tested 290 nasal wash specimens from Filipino children <2 years of age with respiratory tract infections using culture and 3 PCR methods—EraGen, Luminex, and the GIS PathChip. The PathChip had good diagnostic accuracy, ranging from 85.9% (95% confidence interval [CI], 81.3 to 89.7%) for rhinovirus/enteroviruses to 98.6% (95% CI, 96.5 to 99.6%) for PIV 2, compared to the other methods and additionally identified a number of viruses not detected by these methods.",,"['Simões, Eric A. F.', 'Patel, Champa', 'Sung, Wing-Kin', 'Lee, Charlie W. H.', 'Loh, Kuan Hon', 'Lucero, Marilla', 'Nohynek, Hanna', 'Nai, Geraldine', 'Thien, Pei Ling', 'Koh, Chee Wee', 'Chan, Yang Sun', 'Ma, Jianmin', 'Maurer-Stroh, Sebastian', 'Carosone-Link, Phyllis', 'Hibberd, Martin L.', 'Wong, Christopher W.', None]",,,,
,PMC,High Rates of Detection of Respiratory Viruses in the Nasal Washes and Mucosae of Patients with Chronic Rhinosinusitis,http://dx.doi.org/10.1128/JCM.02806-12,PMC3592049,,,"Respiratory viral infections are often implicated as triggers of chronic rhinosinusitis (CRS) flare-ups. However, there is a paucity of respiratory viral surveillance studies in CRS patients, and such studies could elucidate the potential role of viruses in promoting symptoms and aggravating mucosal inflammation. Therefore, a prospective case-control study was conducted to determine the prevalence of respiratory viruses in CRS patients and non-CRS controls. Nasal lavage fluids and turbinate epithelial cells were collected prospectively from 111 CRS patients and 50 controls. Multiplex PCR was used to identify common respiratory viruses in both sample types and the infection rate was compared between groups. Respiratory viruses were detected in 50.5% of lavage samples and in 64.0% of scraping samples from CRS patients. The overall infection rate was significantly different in CRS patients and controls (odds ratio, 2.9 in lavage and 4.1 in scraping samples). Multiple viral infections were detected more frequently in lavage samples from CRS patients than those from controls (P < 0.01; odds ratio, 7.7). Rhinovirus was the most prevalent virus and the only virus with a significantly different infection rate in CRS patients and controls in both samples (odds ratio, 3.2 in lavage and 3.4 in scraping samples). This study detected a higher prevalence of respiratory viruses in CRS patients than controls, suggesting that there may be significant associations between inflammation of CRS and respiratory viruses, particularly rhinovirus. Further studies should investigate the exact role of highly prevalent respiratory viruses in CRS patients during symptomatic aggravation and ongoing mucosal inflammation.",,"['Cho, Gye Song', 'Moon, Byung-Jae', 'Lee, Bong-Jae', 'Gong, Chang-Hoon', 'Kim, Nam Hee', 'Kim, You-Sun', 'Kim, Hun Sik', 'Jang, Yong Ju']",,,,
,PMC,Reversion of Somatic Mutations of the Respiratory Syncytial Virus-Specific Human Monoclonal Antibody Fab19 Reveal a Direct Relationship Between Association Rate and Neutralizing Potency,http://dx.doi.org/10.4049/jimmunol.1202964,PMC3608519,,,"The role of affinity in determining neutralizing potency of monoclonal antibodies directed against viruses is not well understood. We investigated the kinetic, structural, and functional advantage conferred by individual naturally-occurring somatic mutations in the antibody heavy chain variable region of Fab19, a well-described neutralizing human monoclonal antibody directed to respiratory syncytial virus (RSV). Comparison of the affinity-matured antibody Fab19 with recombinant Fab19 antibodies that were variants containing reverted amino acids from the inferred unmutated ancestor sequence revealed the molecular basis for affinity maturation of this antibody. Enhanced binding was achieved through mutations in the third heavy chain complementary determining region (HCDR3) that conferred a markedly faster on-rate and a desirable increase in antiviral neutralizing activity. In contrast, most somatic mutations in the HCDR1 and HCDR2 regions did not significantly enhance antigen binding or antiviral activity. We observed a direct relationship between the measured association rate (K(on)) for F protein and antiviral activity. Modeling studies of the structure of the antigen-antibody complex suggested the HCDR3 loop interacts with the antigenic site A surface loop of the RSV F protein, previously shown to contain the epitope for this antibody by experimentation. These studies define a direct relationship of affinity and neutralizing activity for a viral glycoprotein-specific human monoclonal antibody.",,"['Bates, John T.', 'Keefer, Christopher J.', 'Utley, Thomas J.', 'Correia, Bruno E.', 'Schief, William R.', 'Crowe, James E.']",,,,
,PMC,Nonparametric survival analysis of infectious disease data,http://dx.doi.org/10.1111/j.1467-9868.2012.01042.x,PMC3681432,,,"This paper develops nonparametric methods based on contact intervals for the analysis of infectious disease data. The contact interval from person i to person j is the time between the onset of infectiousness in i and infectious contact from i to j, where we define infectious contact as a contact sufficient to infect a susceptible individual. The hazard function of the contact interval distribution equals the hazard of infectious contact from i to j, so it provides a summary of the evolution of infectiousness over time. When who-infects-whom is observed, the Nelson-Aalen estimator produces an unbiased estimate of the cumulative hazard function of the contact interval distribution. When who-infects-whom is not observed, we use an EM algorithm to average the Nelson-Aalen estimates from all possible combinations of who-infected-whom consistent with the observed data. This converges to a nonparametric maximum likelihood estimate of the cumulative hazard function that we call the marginal Nelson-Aalen estimate. We study the behavior of these methods in simulations and use them to analyze household surveillance data from the 2009 influenza A(H1N1) pandemic.",,"Kenah, Eben",,,,
,PMC,From mice to women: the conundrum of immunity to infection during pregnancy,http://dx.doi.org/10.1016/j.jri.2012.10.015,PMC3748615,,,"Resistance to infection is the ability of the host to evoke a strong immune response sufficient to eliminate the infectious agent. In contrast, maternal tolerance to the fetus necessitates careful regulation of immune responses. Successful pregnancy requires the maternal host to effectively balance the opposing processes of maternal immune reactivity and tolerance to the fetus. However, this balance can be perturbed by infections which are recognized as the major cause of adverse pregnancy outcome including pre-term labor. Select pathogens also pose a serious threat of severe maternal illness. These include intracellular and chronic pathogens that have evolved immune evasive strategies. Murine models of intracellular bacteria and parasites that mimic pathogenesis of infection in humans have been developed. While human epidemiological studies provide insight into maternal immunity to infection, experimental infection in pregnant mice is a vital tool to unravel the complex molecular mechanisms of placental infection, congenital transmission and maternal illness. We will provide a comprehensive review of the pathogenesis of several infection models in pregnant mice and their clinical relevance. These models have revealed the immunological function of the placenta in responding to, and resisting infection. Murine feto-placental infection provides an effective way to evaluate new intervention strategies for managing infections during pregnancy, adverse fetal outcome and long-term effects on the offspring and mother.",,"['Krishnan, Lakshmi', 'Nguyen, Tina', 'McComb, Scott']",,,,
,PMC,The Acetyl-Esterase Activity of the Hemagglutinin-Esterase Protein of Human Coronavirus OC43 Strongly Enhances the Production of Infectious Virus,http://dx.doi.org/10.1128/JVI.02699-12,PMC3592170,,,"Most betacoronaviruses possess an hemagglutinin-esterase (HE) protein, which appears to play a role in binding to or release from the target cell. Since this HE protein possesses an acetyl-esterase activity that removes acetyl groups from O-acetylated sialic acid, a role as a receptor-destroying enzyme has been postulated. However, the precise function of HE and of its enzymatic activity remains poorly understood. Making use of neutralizing antibody and of molecular clones of recombinant human coronavirus OC43 (HCoV-OC43), our results suggest that the HE protein of this HCoV could be associated with infection of target cells and, most notably, is important in the production of infectious viral particles. Indeed, after transfecting BHK-21 cells with various cDNA infectious clones of HCoV-OC43, either lacking the HE protein or bearing an HE protein with a nonfunctional acetyl-esterase enzymatic activity, we were reproducibly unable to detect recombinant infectious viruses compared to the reference infectious HCoV-OC43 clone pBAC-OC43(FL). Complementation experiments, using BHK-21 cells expressing wild-type HE, either transiently or in a stable ectopic expression, demonstrate that this protein plays a very significant role in the production of infectious recombinant coronaviral particles that can subsequently more efficiently infect susceptible epithelial and neuronal cells. Even though the S protein is the main viral factor influencing coronavirus infection of susceptible cells, our results taken together indicate that a functionally active HE protein enhances the infectious properties of HCoV-OC43 and contributes to efficient virus dissemination in cell culture.",,"['Desforges, Marc', 'Desjardins, Jessica', 'Zhang, Chengsheng', 'Talbot, Pierre J.']",,,,
,PMC,Astrocyte-Derived CXCL10 Drives Accumulation of Antibody-Secreting Cells in the Central Nervous System during Viral Encephalomyelitis,http://dx.doi.org/10.1128/JVI.03307-12,PMC3592145,,,"Microbial infections of the central nervous system (CNS) are often associated with local accumulation of antibody (Ab)-secreting cells (ASC). By providing a source of Ab at the site of infection, CNS-localized ASC play a critical role in acute viral control and in preventing viral recrudescence. Following coronavirus-induced encephalomyelitis, the CNS accumulation of ASC is chemokine (C-X-C motif) receptor 3 (CXCR3) dependent. This study demonstrates that CNS-expressed CXCR3 ligand CXCL10 is the critical chemokine regulating ASC accumulation. Impaired ASC recruitment in CXCL10(−/−) but not CXCL9(−/−) mice was consistent with reduced CNS IgG and κ-light chain mRNA and virus-specific Ab. Moreover, the few ASC recruited to the CNS in CXCL10(−/−) mice were confined to the vasculature, distinct from the parenchymal localization in wild-type and CXCL9(−/−) mice. However, neither CXCL9 nor CXCL10 deficiency diminished neutralizing serum Ab, supporting a direct role for CXCL10 in ASC migration. T cell accumulation, localization, and effector functions were also not affected in either CXCL9(−/−) or CXCL10(−/−) mice, consistent with similar control of infectious virus. There was also no evidence for dysregulation of chemokines or cytokines involved in ASC regulation. The distinct roles of CXCL9 and CXCL10 in ASC accumulation rather coincided with their differential localization. While CXCL10 was predominantly expressed by astrocytes, CXCL9 expression was confined to the vasculature/perivascular spaces. These results suggest that CXCL10 is critical for two phases: recruitment of ASC to the CNS vasculature and ASC entry into the CNS parenchyma.",,"['Phares, Timothy W.', 'Stohlman, Stephen A.', 'Hinton, David R.', 'Bergmann, Cornelia C.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00205-13,PMC3592141,,,,,,,,,
,PMC,Solution Structure of Mouse Hepatitis Virus (MHV) nsp3a and Determinants of the Interaction with MHV Nucleocapsid (N) Protein,http://dx.doi.org/10.1128/JVI.03112-12,PMC3592139,,,"Coronaviruses (CoVs) are positive-sense, single-stranded, enveloped RNA viruses that infect a variety of vertebrate hosts. The CoV nucleocapsid (N) protein contains two structurally independent RNA binding domains, designated the N-terminal domain (NTD) and the dimeric C-terminal domain (CTD), joined by a charged linker region rich in serine and arginine residues (SR-rich linker). An important goal in unraveling N function is to molecularly characterize N-protein interactions. Recent genetic evidence suggests that N interacts with nsp3a, a component of the viral replicase. Here we present the solution nuclear magnetic resonance (NMR) structure of mouse hepatitis virus (MHV) nsp3a and show, using isothermal titration calorimetry, that MHV N219, an N construct that extends into the SR-rich linker (residues 60 to 219), binds cognate nsp3a with high affinity (equilibrium association constant [K(a)], [1.4 ± 0.3] × 10(6) M(−1)). In contrast, neither N197, an N construct containing only the folded NTD (residues 60 to 197), nor the CTD dimer (residues 260 to 380) binds nsp3a with detectable affinity. This indicates that the key nsp3a binding determinants localize to the SR-rich linker, a finding consistent with those of reverse genetics studies. NMR chemical shift perturbation analysis reveals that the N-terminal region of an MHV N SR-rich linker peptide (residues 198 to 230) binds to the acidic face of MHV nsp3a containing the acidic α2 helix with an affinity (expressed as K(a)) of 8.1 × 10(3) M(−1). These studies reveal that the SR-rich linker of MHV N is necessary but not sufficient to maintain this high-affinity binding to N.",,"['Keane, Sarah C.', 'Giedroc, David P.']",,,,
,PMC,Mandarin Fish Caveolin 1 Interaction with Major Capsid Protein of Infectious Spleen and Kidney Necrosis Virus and Its Role in Early Stages of Infection,http://dx.doi.org/10.1128/JVI.00552-12,PMC3592132,,,"Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus from the family Iridoviridae. ISKNV is one of the major agents that cause mortality and economic losses to the freshwater fish culture industry in Asian countries, particularly for mandarin fish (Siniperca chuatsi). In the present study, we report that the interaction of mandarin fish caveolin 1 (mCav-1) with the ISKNV major capsid protein (MCP) was detected by using a virus overlay assay and confirmed by pulldown assay and coimmunoprecipitation. This interaction was independent of the classic caveolin 1 scaffolding domain (CSD), which is responsible for interacting with several signaling proteins and receptors. Confocal immunofluorescence microscopy showed that ISKNV MCP colocalized with mCav-1 in the perinuclear region of virus-infected mandarin fish fry (MFF-1) cells, which appeared as soon as 4 h postinfection. Subcellular fractionation analysis showed that ISKNV MCP was associated with caveolae in the early stages of viral infection. RNA interference silencing of mCav-1 did not change virus-cell binding but efficiently inhibited the entry of virions into the cell. Taken together, these results suggested that mCav-1 plays an important role in the early stages of ISKNV infection.",,"['Jia, Kun-Tong', 'Wu, Yan-Yan', 'Liu, Zhao-Yu', 'Mi, Shu', 'Zheng, Yi-Wen', 'He, Jian', 'Weng, Shao-Ping', 'Li, Shengwen Calvin', 'He, Jian-Guo', 'Guo, Chang-Jun']",,,,
,PMC,Filoviruses Utilize Glycosaminoglycans for Their Attachment to Target Cells,http://dx.doi.org/10.1128/JVI.01621-12,PMC3592117,,,"Filoviruses are the cause of severe hemorrhagic fever in human and nonhuman primates. The envelope glycoprotein (GP), responsible for both receptor binding and fusion of the virus envelope with the host cell membrane, has been demonstrated to interact with multiple molecules in order to enhance entry into host cells. Here we have demonstrated that filoviruses utilize glycosaminoglycans, and more specifically heparan sulfate proteoglycans, for their attachment to host cells. This interaction is mediated by GP and does not require the presence of the mucin domain. Both the degree of sulfation and the structure of the carbohydrate backbone play a role in the interaction with filovirus GPs. This new step of filovirus interaction with host cells can potentially be a new target for antiviral strategies. As such, we were able to inhibit filovirus GP-mediated infection using carrageenan, a broad-spectrum microbicide that mimics heparin, and also using the antiviral dendrimeric peptide SB105-A10, which interacts with heparan sulfate, antagonizing the binding of the virus to cells.",,"['Salvador, Beatriz', 'Sexton, Nicole R.', 'Carrion, Ricardo', 'Nunneley, Jerritt', 'Patterson, Jean L.', 'Steffen, Imke', 'Lu, Kai', 'Muench, Marcus O.', 'Lembo, David', 'Simmons, Graham']",,,,
,PMC,A Mutation in the Ebola Virus Envelope Glycoprotein Restricts Viral Entry in a Host Species- and Cell-Type-Specific Manner,http://dx.doi.org/10.1128/JVI.01598-12,PMC3592116,,,"Zaire Ebola virus (EBOV) is a zoonotic pathogen that causes severe hemorrhagic fever in humans. A single viral glycoprotein (GP) mediates viral attachment and entry. Here, virus-like particle (VLP)-based entry assays demonstrate that a GP mutant, GP-F88A, which is defective for entry into a variety of human cell types, including antigen-presenting cells (APCs), such as macrophages and dendritic cells, can mediate viral entry into mouse CD11b(+) APCs. Like that of wild-type GP (GP-wt), GP-F88A-mediated entry occurs via a macropinocytosis-related pathway and requires endosomal cysteine proteases and an intact fusion peptide. Several additional hydrophobic residues lie in close proximity to GP-F88, including L111, I113, L122, and F225. GP mutants in which these residues are mutated to alanine displayed preferential and often impaired entry into several cell types, although not in a species-specific manner. Niemann-Pick C1 (NPC1) protein is an essential filovirus receptor that binds directly to GP. Overexpression of NPC1 was recently demonstrated to rescue GP-F88A-mediated entry. A quantitative enzyme-linked immunosorbent assay (ELISA) demonstrated that while the F88A mutation impairs GP binding to human NPC1 by 10-fold, it has little impact on GP binding to mouse NPC1. Interestingly, not all mouse macrophage cell lines permit GP-F88A entry. The IC-21 cell line was permissive, whereas RAW 264.7 cells were not. Quantitative reverse transcription (RT)-PCR assays demonstrate higher NPC1 levels in GP-F88A permissive IC-21 cells and mouse peritoneal macrophages than in RAW 264.7 cells. Cumulatively, these studies suggest an important role for NPC1 in the differential entry of GP-F88A into mouse versus human APCs.",,"['Martinez, Osvaldo', 'Ndungo, Esther', 'Tantral, Lee', 'Miller, Emily Happy', 'Leung, Lawrence W.', 'Chandran, Kartik', 'Basler, Christopher F.']",,,,
,PMC,Influenza A Virus NS1 Induces G(0)/G(1) Cell Cycle Arrest by Inhibiting the Expression and Activity of RhoA Protein,http://dx.doi.org/10.1128/JVI.03176-12,PMC3592114,,,"Influenza A virus is an important pathogenic virus known to induce host cell cycle arrest in G(0)/G(1) phase and create beneficial conditions for viral replication. However, how the virus achieves arrest remains unclear. We investigated the mechanisms underlying this process and found that the nonstructural protein 1 (NS1) is required. Based on this finding, we generated a viable influenza A virus (H1N1) lacking the entire NS1 gene to study the function of this protein in cell cycle regulation. In addition to some cell cycle regulators that were changed, the concentration and activity of RhoA protein, which is thought to be pivotal for G(1)/S phase transition, were also decreased with overexpressing NS1. And in the meantime, the phosphorylation level of cell cycle regulator pRb, downstream of RhoA kinase, was decreased in an NS1-dependent manner. These findings indicate that the NS1 protein induces G(0)/G(1) cell cycle arrest mainly through interfering with the RhoA/pRb signaling cascade, thus providing favorable conditions for viral protein accumulation and replication. We further investigated the NS1 protein of avian influenza virus (H5N1) and found that it can also decrease the expression and activity of RhoA, suggesting that the H5N1 virus may affect the cell cycle through the same mechanism. The NS1/RhoA/pRb cascade, which can induce the G(0)/G(1) cell cycle arrest identified here, provides a unified explanation for the seemingly different NS1 functions involved in viral replication events. Our findings shed light on the mechanism of influenza virus replication and open new avenues for understanding the interaction between pathogens and hosts.",,"['Jiang, Wei', 'Wang, Qingtao', 'Chen, Shuai', 'Gao, Shijuan', 'Song, Liping', 'Liu, Pengyu', 'Huang, Wenlin']",,,,
,PMC,Transgenic CCL2 Expression in the Central Nervous System Results in a Dysregulated Immune Response and Enhanced Lethality after Coronavirus Infection,http://dx.doi.org/10.1128/JVI.03089-12,PMC3571407,,,"Chemokine (C-C motif) ligand 2 (CCL2), a chemoattractant for macrophages, T cells, and cells expressing CCR2, is upregulated during acute and chronic inflammation. CCL2 has been implicated in both proinflammatory and anti-inflammatory responses and has been suggested as a target for therapy in some inflammatory disorders. To examine the role of CCL2 during virus infection, we infected mice transgenically expressing CCL2 in the central nervous system (CCL2 Tg) with an attenuated neurotropic coronavirus (rJ2.2 strain of mouse hepatitis virus). Infection of wild-type mice with rJ2.2 results in mild acute encephalitis, followed by a nonlethal, chronic demyelinating disease. Proinflammatory innate and adaptive immune responses mediate virus clearance. In marked contrast, CCL2 Tg mice infected with rJ2.2 ineffectively cleared virus and rapidly succumbed to the infection. CCL2 Tg mice mounted a dysregulated immune response, characterized by augmented accumulation of regulatory Foxp3(+)CD4(+) T cells and of nitric-oxide- and YM-1-expressing macrophages and microglia, suggestive of mixed M1/M2 macrophage activation. Further, macrophages from infected CCL2 Tg brains relative to non-Tg controls were less activated/mature, expressing lower levels of major histocompatibility complex class II (MHC-II), CD86, and CD40. Collectively, these results show that persistent CCL2 overexpression establishes and sustains an immunological milieu that is both inflammatory and immunosuppressive and predisposes mice to a defective immune response to a minimally lethal virus.",,"['Trujillo, Jonathan A.', 'Fleming, Erica L.', 'Perlman, Stanley']",,,,
,PMC,Structure of Alphacoronavirus Transmissible Gastroenteritis Virus nsp1 Has Implications for Coronavirus nsp1 Function and Evolution,http://dx.doi.org/10.1128/JVI.03163-12,PMC3571401,,,"Coronavirus nsp1 has been shown to induce suppression of host gene expression and to interfere with the host immune response. However, the mechanism is currently unknown. The only available structural information on coronavirus nsp1 is the nuclear magnetic resonance (NMR) structure of the N-terminal domain of nsp1 from severe acute respiratory syndrome coronavirus (SARS-CoV) from the betacoronavirus genus. Here we present the first nsp1 structure from an alphacoronavirus, transmissible gastroenteritis virus (TGEV) nsp1. It displays a six-stranded β-barrel fold with a long alpha helix on the rim of the barrel, a fold shared with SARS-CoV nsp1(13–128). Contrary to previous speculation, the TGEV nsp1 structure suggests that coronavirus nsp1s have a common origin, despite the lack of sequence homology. However, comparisons of surface electrostatics, shape, and amino acid conservation between the alpha- and betacoronaviruses lead us to speculate that the mechanism for nsp1-induced suppression of host gene expression might be different in these two genera.",,"Jansson, Anna M.",,,,
,PMC,The PA-Gene-Mediated Lethal Dissemination and Excessive Innate Immune Response Contribute to the High Virulence of H5N1 Avian Influenza Virus in Mice,http://dx.doi.org/10.1128/JVI.02891-12,PMC3571398,,,"Highly pathogenic H5N1 influenza A virus remains a substantial threat to public health. To understand the molecular basis and host mechanism for the high virulence of H5N1 viruses in mammals, we compared two H5N1 isolates which have similar genetic backgrounds but greatly differ in their virulence in mice. A/Chicken/Jiangsu/k0402/2010 (CK10) is highly pathogenic, whereas A/Goose/Jiangsu/k0403/2010 (GS10) is nonpathogenic. We first showed that CK10 elicited a more potent innate immune response than did GS10 in mouse lungs by increasing the number and expression levels of activated genes. We then generated a series of reassortants between the two viruses and evaluated their virulence in mice. Inclusion of the CK10 PA gene in the GS10 background resulted in a dramatic increase in virulence. Conversely, expression of the GS10 PA gene in the CK10 background significantly attenuated the virulence. These results demonstrated that the PA gene mainly determines the pathogenicity discrepancy between CK10 and GS10 in mice. We further determined that arginine (R) at position 353 of the PA gene contributes to the high virulence of CK10 in mice. The reciprocal substitution at position 353 in PA or the exchange of the entire PA gene largely caused the transfer of viral phenotypes, including virus replication, polymerase activity, and manipulation of the innate response, between CK10 and GS10. We therefore defined a novel molecular marker associated with the high virulence of H5N1 influenza viruses, providing further insights into the pathogenesis of H5N1 viruses in mammals.",,"['Hu, Jiao', 'Hu, Zenglei', 'Song, Qingqing', 'Gu, Min', 'Liu, Xiaowen', 'Wang, Xiaoquan', 'Hu, Shunlin', 'Chen, Chaoyang', 'Liu, Huimou', 'Liu, Wenbo', 'Chen, Sujuan', 'Peng, Daxin', 'Liu, Xiufan']",,,,
,PMC,Complex Alternative Cytoplasmic Protein Isoforms of the Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Generated through Noncanonical Translation Initiation,http://dx.doi.org/10.1128/JVI.03061-12,PMC3571394,,,"Kaposi's sarcoma-associated herpesvirus (KSHV) latency associated-nuclear antigen 1 (LANA1) protein is constitutively expressed in all KSHV-infected cells, as well as in all forms of KSHV-associated malignancies. LANA1 is a multifunctional KSHV oncoprotein containing multiple repeat sequences that is important for viral episome maintenance and the regulation of cellular and viral gene expression. We characterize here multiple LANA1 isoforms and show that ∼50% of LANA1 is naturally generated as N-terminally truncated shoulder proteins that are detected on SDS-PAGE as faster-migrating shoulder bands designated LANA1(S). Higher-molecular-weight LANA1(S) isoforms initiate downstream at noncanonical sites within the N-terminal region, whereas lower-molecular-weight LANA1(S) isoforms initiate downstream within the central repeat 1 domain. LANA1(S) proteins lack an N-terminal nuclear localization signal motif, and some isoforms differ from full-length, canonical LANA1 by localizing to perinuclear and cytoplasmic sites. Although LANA1 has until now been assumed to be solely active in the nucleus, this finding indicates that this major KSHV oncoprotein may have cytoplasmic activities as well. KSHV overcomes its limited genetic coding capacity by generating alternatively initiated protein isoforms that may have distinct biological functions.",,"['Toptan, Tuna', 'Fonseca, Lidia', 'Kwun, Hyun Jin', 'Chang, Yuan', 'Moore, Patrick S.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00038-13,PMC3571371,,,,,,,,,
,PMC,Comparative Genomics of Carp Herpesviruses,http://dx.doi.org/10.1128/JVI.03206-12,PMC3571366,,,"Three alloherpesviruses are known to cause disease in cyprinid fish: cyprinid herpesviruses 1 and 3 (CyHV1 and CyHV3) in common carp and koi and cyprinid herpesvirus 2 (CyHV2) in goldfish. We have determined the genome sequences of CyHV1 and CyHV2 and compared them with the published CyHV3 sequence. The CyHV1 and CyHV2 genomes are 291,144 and 290,304 bp, respectively, in size, and thus the CyHV3 genome, at 295,146 bp, remains the largest recorded among the herpesviruses. Each of the three genomes consists of a unique region flanked at each terminus by a sizeable direct repeat. The CyHV1, CyHV2, and CyHV3 genomes are predicted to contain 137, 150, and 155 unique, functional protein-coding genes, respectively, of which six, four, and eight, respectively, are duplicated in the terminal repeat. The three viruses share 120 orthologous genes in a largely colinear arrangement, of which up to 55 are also conserved in the other member of the genus Cyprinivirus, anguillid herpesvirus 1. Twelve genes are conserved convincingly in all sequenced alloherpesviruses, and two others are conserved marginally. The reference CyHV3 strain has been reported to contain five fragmented genes that are presumably nonfunctional. The CyHV2 strain has two fragmented genes, and the CyHV1 strain has none. CyHV1, CyHV2, and CyHV3 have five, six, and five families of paralogous genes, respectively. One family unique to CyHV1 is related to cellular JUNB, which encodes a transcription factor involved in oncogenesis. To our knowledge, this is the first time that JUNB-related sequences have been reported in a herpesvirus.",,"['Davison, Andrew J.', 'Kurobe, Tomofumi', 'Gatherer, Derek', 'Cunningham, Charles', 'Korf, Ian', 'Fukuda, Hideo', 'Hedrick, Ronald P.', 'Waltzek, Thomas B.']",,,,
,PMC,Ocular Tropism of Respiratory Viruses,http://dx.doi.org/10.1128/MMBR.00058-12,PMC3591987,,,"SUMMARY: Respiratory viruses (including adenovirus, influenza virus, respiratory syncytial virus, coronavirus, and rhinovirus) cause a broad spectrum of disease in humans, ranging from mild influenza-like symptoms to acute respiratory failure. While species D adenoviruses and subtype H7 influenza viruses are known to possess an ocular tropism, documented human ocular disease has been reported following infection with all principal respiratory viruses. In this review, we describe the anatomical proximity and cellular receptor distribution between ocular and respiratory tissues. All major respiratory viruses and their association with human ocular disease are discussed. Research utilizing in vitro and in vivo models to study the ability of respiratory viruses to use the eye as a portal of entry as well as a primary site of virus replication is highlighted. Identification of shared receptor-binding preferences, host responses, and laboratory modeling protocols among these viruses provides a needed bridge between clinical and laboratory studies of virus tropism.",,"['Belser, Jessica A.', 'Rota, Paul A.', 'Tumpey, Terrence M.']",,,,
,PMC,Angiotensin and Systems Thinking: Wrapping Your Mind Around the Big Picture,,PMC3603174,,,,,"Smith, Gary Robert",,,,
,PMC,Prospective Detection of Respiratory Pathogens in Symptomatic Children with Cancer,http://dx.doi.org/10.1097/INF.0b013e31827bd619,PMC4725698,,,"BACKGROUND: The data on human rhinovirus (HRV), coronavirus (hCoV), bocavirus (hBoV), metapneumovirus (hMPV), Chlamydophila pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis infections in children with cancer is limited. METHODS: We sought to determine prospectively the prevalence of respiratory pathogens in these children, using multiplexed-PCR. RESULTS: We enrolled 253 children with upper, or lower respiratory tract infection (URTI/LRTI) during a one year period. A respiratory virus was detected in 193 (76%) patients; 156 (81%) patients had URTI. Human rhinovirus was the most common virus detected in 97 (62%) and 24 (65%) patients with URTI and LRTI, respectively. Leukemia or lymphoma (LL) was the most common underlying diagnosis in 95 (49%) patients followed by solid tumor 47 (24%), post-hematopoietic stem cell transplant (HCT) 28 (15%), and brain tumor in 23 (12%) patients. By multiple logistic regression analysis hBoV was the most commonly detected respiratory virus in patients with LRTI (P = 0.008; odds ratio, 4.52; 95% confidence interval, 1.48-13.79). Co-infection with more than 1 virus was present in 47 (24%) patients, and did not increase the risk for LRTI. Two (0.7%) patients succumbed to LRTI from parainfluenza virus (PIV)-3 and respiratory syncytial virus/HRV infection, respectively. C.pneumoniae and M.pneumoniae were detected in 4 and 3 patients, respectively. CONCLUSIONS: HRV was the most common virus detected in children with cancer and post-HCT hospitalized with an acute respiratory illness, and was not associated with increased morbidity. Prospective studies with viral load determination and asymptomatic controls are needed to study the association of these emerging respiratory viruses with LRTI in children with cancer and post-HCT.",,"['Srinivasan, Ashok', 'Gu, Zhengming', 'Smith, Teresa', 'Morgenstern, Markus', 'Sunkara, Anusha', 'Kang, Guolian', 'Srivastava, Deo K.', 'Gaur, Aditya H.', 'Leung, Wing', 'Hayden, Randall T.']",,,,
,PMC,"Personal genomes, quantitative dynamic omics and personalized medicine",http://dx.doi.org/10.1007/s40484-013-0005-3,PMC4366006,,,"The rapid technological developments following the Human Genome Project have made possible the availability of personalized genomes. As the focus now shifts from characterizing genomes to making personalized disease associations, in combination with the availability of other omics technologies, the next big push will be not only to obtain a personalized genome, but to quantitatively follow other omics. This will include transcriptomes, proteomes, metabolomes, antibodyomes, and new emerging technologies, enabling the profiling of thousands of molecular components in individuals. Furthermore, omics profiling performed longitudinally can probe the temporal patterns associated with both molecular changes and associated physiological health and disease states. Such data necessitates the development of computational methodology to not only handle and descriptively assess such data, but also construct quantitative biological models. Here we describe the availability of personal genomes and developing omics technologies that can be brought together for personalized implementations and how these novel integrated approaches may effectively provide a precise personalized medicine that focuses on not only characterization and treatment but ultimately the prevention of disease.",,"['Mias, George I.', 'Snyder, Michael']",,,,
,PMC,Intraepithelial type 1 innate lymphoid cells are a unique subset of cytokine responsive interferon-γ-producing cells,http://dx.doi.org/10.1016/j.immuni.2013.02.010,PMC3634355,,,"Mucosal innate lymphoid cell (ILC) subsets promote immune responses to pathogens by producing distinct signature cytokines in response to changes in the cytokine microenvironment. We previously identified human ILC3 distinguished by interleukin-22 (IL-22) secretion. Here we characterized a human ILC1 subset that produced Interferon-γ in response to IL-12 and IL-15, had a unique integrin profile, intraepithelial location, hallmarks of TGF-β imprinting and a memory-activated phenotype. Because tissue-resident memory CD8(+) T cells share this profile, intraepithelial ILC1 may be their innate counterparts. In mice, intraepithelial ILC1 were distinguished by CD160 expression and required Nfil3-and Tbx21-encoded transcription factors for development, but not IL-15 receptor-α, indicating that intraepithelial ILC1 are distinct from conventional NK cells. Intraepithelial ILC1 were amplified in Crohn’s disease patients and contributed to pathology in the anti-CD40-induced colitis model in mice. Thus, intraepithelial ILC1 may initiate interferon-γ responses against pathogens, but contribute to pathology when dysregulated.",,"['Fuchs, Anja', 'Vermi, William', 'Lee, Jacob S.', 'Lonardi, Silvia', 'Gilfillan, Susan', 'Newberry, Rodney D.', 'Cella, Marina', 'Colonna, Marco']",,,,
,PMC,"Structural biology of the writers, readers, and erasers in mono- and poly(ADP-ribose) mediated signaling",http://dx.doi.org/10.1016/j.mam.2013.02.002,PMC3726583,,,"ADP-ribosylation of proteins regulates protein activities in various processes including transcription control, chromatin organization, organelle assembly, protein degradation, and DNA repair. Modulating the proteins involved in the metabolism of ADP-ribosylation can have therapeutic benefits in various disease states. Protein crystal structures can help understand the biological functions, facilitate detailed analysis of single residues, as well as provide a basis for development of small molecule effectors. Here we review recent advances in our understanding of the structural biology of the writers, readers, and erasers of ADP-ribosylation.",,"['Karlberg, Tobias', 'Langelier, Marie-France', 'Pascal, John M.', 'Schüler, Herwig']",,,,
,PMC,SOCS proteins in development and disease,,PMC3714205,,,"Cytokine and growth factor signaling mediates essential roles in the differentiation, proliferation, survival and function of a number of cell lineages. This is achieved via specific receptors located on the surface of target cells, with ligand binding activating key intracellular signal transduction cascades to mediate the requisite cellular outcome. Effective resolution of receptor signaling is also essential, with excessive signaling having the potential for pathological consequences. The Suppressor of cytokine signaling (SOCS) family of proteins represent one important mechanism to extinguish cytokine and growth factor receptor signaling. There are 8 SOCS proteins in mammals; SOCS1-7 and the alternatively named Cytokine-inducible SH2-containing protein (CISH). SOCS1-3 and CISH are predominantly associated with the regulation of cytokine receptor signaling, while SOCS4-7 are more commonly involved in the control of Receptor tyrosine kinase (RTK) signaling. Individual SOCS proteins are typically induced by specific cytokines and growth factors, thereby generating a negative feedback loop. As a consequence of their regulatory properties, SOCS proteins have important functions in development and homeostasis, with increasing recognition of their role in disease, particularly their tumor suppressor and anti-inflammatory functions. This review provides a synthesis of our current understanding of the SOCS family, with an emphasis on their immune and hematopoietic roles.",,"['Trengove, Monique C', 'Ward, Alister C']",,,,
,PMC,The Angelman Syndrome Protein Ube3a/E6AP Is Required for Golgi Acidification and Surface Protein Sialylation,http://dx.doi.org/10.1523/JNEUROSCI.1930-11.2013,PMC3783510,,,"Angelman syndrome (AS) is a severe disorder of postnatal brain development caused by neuron-specific loss of the HECT (homologous to E6AP carboxy terminus) domain E3 ubiquitin ligase Ube3a/E6AP. The cellular role of Ube3a remains enigmatic despite recent descriptions of synaptic and behavioral deficits in AS mouse models. Although neuron-specific imprinting is thought to limit the disease to the brain, Ube3a is expressed ubiquitously, suggesting a broader role in cellular function. In the current study, we demonstrate a profound structural disruption and cisternal swelling of the Golgi apparatus (GA) in the cortex of AS (UBE3A(m−/p+)) mice. In Ube3a knockdown cell lines and UBE3A(m−/p+) cortical neurons, the GA is severely under-acidified, leading to osmotic swelling. Both in vitro and in vivo, the loss of Ube3a and corresponding elevated pH of the GA is associated with a marked reduction in protein sialylation, a process highly dependent on intralumenal Golgi pH. Altered ion homeostasis of the GA may provide a common cellular pathophysiology underlying the diverse plasticity and neurodevelopmental deficits associated with AS.",,"['Condon, Kathryn H.', 'Ho, Jianghai', 'Robinson, Camenzind G.', 'Hanus, Cyril', 'Ehlers, Michael D.']",,,,
,PMC,Protein Analysis by Shotgun/Bottom-up Proteomics,http://dx.doi.org/10.1021/cr3003533,PMC3751594,,,,,"['Zhang, Yaoyang', 'Fonslow, Bryan R.', 'Shan, Bing', 'Baek, Moon-Chang', 'Yates, John R.']",,,,
,PMC,The Lipophilic Bullet Hits the Targets: Medicinal Chemistry of Adamantane Derivatives,http://dx.doi.org/10.1021/cr100264t,PMC3650105,,,,,"['Wanka, Lukas', 'Iqbal, Khalid', 'Schreiner, Peter R.']",,,,
,PMC,"Characterisation of a monoclonal antibody detecting Atlantic salmon endothelial and red blood cells, and its association with the infectious salmon anaemia virus cell receptor",http://dx.doi.org/10.1111/joa.12033,PMC3633344,,,"Endothelial cells (ECs) line the luminal surfaces of the cardiovascular system and play an important role in cardiovascular functions such as regulation of haemostasis and vasomotor tone. A number of fish and mammalian viruses target these cells in the course of their infection. Infectious salmon anaemia virus (ISAV) attacks ECs and red blood cells (RBCs) of farmed Atlantic salmon (Salmo salar L.), producing the severe disease of infectious salmon anaemia (ISA). The investigation of ISA has up to now been hampered by the lack of a functional marker for ECs in Atlantic salmon in situ. In this study, we report the characterisation and use of a novel monoclonal antibody (MAb) detecting Atlantic salmon ECs (e.g. vessel endothelium, endocardial cells and scavenger ECs) and RBCs. The antibody can be used with immunohistochemistry, IFAT and on Western blots. It appears that the epitope recognised by the antibody is associated with the ISAV cellular receptor. Besides being a tool to identify ECs in situ, it could be useful in further studies of the pathogenicity of ISA. Finally, the detection of an epitope shared by ECs and RBCs agrees with recent findings that these cells share a common origin, thus the MAb can potentially be used to study the ontogeny of these cells in Atlantic salmon.",,"['Aamelfot, Maria', 'Weli, Simon C', 'Dale, Ole B', 'Koppang, Erling O', 'Falk, Knut']",,,,
,PMC,Perceived Competence and Comfort in Respiratory Protection: Results of a Nationwide Survey of Occupational Health Nurses,http://dx.doi.org/10.3928/21650799-20130218-39,PMC4548926,,,"In response to the Institute of Medicine (2011) report Occupational Health Nurses and Respiratory Protection: Improving Education and Training, a nationwide survey was conducted in May 2012 to assess occupational health nurses’ educational preparation, roles, responsibilities, and training needs in respiratory protection. More than 2,000 occupational health nurses responded; 83% perceived themselves as competent, proficient, or expert in respiratory protection, reporting moderate comfort with 12 respiratory program elements. If occupational health nurses had primary responsibility for the respiratory protection program, they were more likely to perceive higher competence and more comfort in respiratory protection, after controlling for occupational health nursing experience, highest education, occupational health nursing certification, industry sector, Association of Occupational Health Professionals in Healthcare membership, taking a National Institute for Occupational Safety and Health spirometry course in the prior 5 years, and perceiving a positive safety culture at work. These survey results document high perceived competence and comfort in respiratory protection. These findings support the development of targeted educational programs and interprofessional competencies for respiratory protection.",,"['Burgel, Barbara J.', 'Novak, Debra', 'Burns, Candace M.', 'Byrd, Annette', 'Carpenter, Holly', 'Gruden, MaryAnn', 'Lachat, Ann', 'Taormina, Deborah']",,,,
,PMC,Epistasis between mutations is host-dependent for an RNA virus,http://dx.doi.org/10.1098/rsbl.2012.0396,PMC3565478,,,"How, and to what extent, does the environment influence the way mutations interact? Do environmental changes affect both the sign and the magnitude of epistasis? Are there any correlations between environments in the variability, sign or magnitude of epistasis? Very few studies have tackled these questions. Here, we addressed them in the context of viral emergence. Most emerging viruses are RNA viruses with small genomes, overlapping reading frames and multifunctional proteins for which epistasis is abundant. Understanding the effect of host species in the sign and magnitude of epistasis will provide insights into the evolutionary ecology of infectious diseases and the predictability of viral emergence.",,"['Lalić, Jasna', 'Elena, Santiago F.']",,,,
,PMC,The Myxovirus Resistance A (MxA) Gene −88G>T Single Nucleotide Polymorphism Is Associated with Prostate Cancer,http://dx.doi.org/10.1016/j.meegid.2013.02.010,PMC3669225,,,"BACKGROUND: Myxovirus (influenza virus) resistance A (MxA) is an interferon stimulated antiviral protein that is required for a complete antiviral response. MxA polymorphism (rs2071430) is located within an Interferon Stimulated Response Element (ISRE) at position −88 in the gene’s promoter region, and it has been associated with increased susceptibility to infections and various diseases. In general, the low promoter activity genotype (GG) promotes susceptibility, whereas the high promoter activity genotype (TT) confers protection to Hepatitis C viral infection. MxA’s role in prostate cancer is not fully understood. Previous literature has shown that MxA may be a mediator of the effect of IFN on normal and tumor cell motility. MxA may act as a tumor suppressor and the level of expression may be a predictor of metastatic potential. Based on this information, in this study we investigated the association of this functional polymorphism (rs2071430) in MxA with prostate cancer. METHODS: Sample size and power was calculated using the PGA software. Genomic DNA from a controls (n=140) and prostate cancer patients (n=164) were used for genotyping SNP rs2071430 on all samples. Statistical analysis was performed using logistic regression model. RESULTS: A significant association was observed between rs2071430 genotype GG and prostate cancer. Individuals harboring the GG genotype are at an increased risk of prostate cancer. Data stratification reveals that the mutant GT genotype offers either offers some protection against prostate cancer in Caucasians. CONCLUSIONS: MxA SNP rs2071430 GG genotype is significantly associated with prostate cancer irrespective of race. However, data stratification also suggests that the GT genotype is under-represented in Caucasian subjects suggesting its role in protection against prostate cancer in Caucasians. Although MxA is primarily implicated in viral infection, but it may be also be associated with prostate cancer. Recent studies have implicated viral and bacterial infections with increased prostate cancer risk. Expression of the high promoter activity genotype may offer resistance to prostate cancer infection and possibly influence clinical outcomes.",,"['Glymph, Shanora', 'Mandal, Sanjay', 'Knowell, Ashley Evans', 'Abebe, Fisseha', 'Chaudhary, Jaideep']",,,,
,PMC,Elevations in D-dimer and C-reactive protein are associated with the development of osteonecrosis of the hip in HIV-infected adults,http://dx.doi.org/10.1097/QAD.0b013e32835c206a,PMC5507350,,,"BACKGROUND: A high incidence of non-traumatic osteonecrosis has been reported in HIV-infected patients. We investigated the levels of D-dimer and C-reactive protein (CRP) in a cohort of HIV-infected adults with and without osteonecrosis of the femoral head. METHODS: 43 HIV-infected patients with osteonecrosis of the femoral head and a comparison group of 50 HIV-infected patients with negative MR imaging of the hips and for whom serial plasma samples were available were included. D-dimer and CRP levels were measured prior to and at the time of diagnosis for osteonecrosis patients, at the time of negative MR imaging of the hips for controls, and ≥6 months later for both groups. RESULTS: Biomarker levels were elevated at the time of diagnosis in the osteonecrosis cohort compared with controls. Median D-dimer value was 0.32 µg/mL in the osteonecrosis group compared to <0.22 µg/mL in the control group (p=0.016). For CRP the corresponding values were 2.52 mg/L and 1.23 mg/L (p=0.003). Post-diagnosis, D-dimer and CRP levels were also elevated in the osteonecrosis patients compared to controls. Linear regression demonstrated a rise in D-dimer levels from pre-diagnosis to diagnosis in the osteonecrosis patients while CRP levels did not change significantly over time. CONCLUSIONS: Compared to controls, patients who developed osteonecrosis had elevated levels of D-dimer and CRP at diagnosis. D-dimer levels increased while CRP levels did not change significantly from pre-diagnosis to diagnosis. These data suggest that patients with higher levels of inflammation are at an increased risk of osteonecrosis.",,"['Morse, Caryn G.', 'Dodd, Lori E.', 'Nghiem, Khanh', 'Costello, Rene', 'Csako, Gyorgy', 'Lane, H. Clifford', 'Lozier, Jay N.', 'Kovacs, Joseph A.']",,,,
,PMC,"Whole transcriptome analysis of the ERα synthetic fragment P(295)‐T311 (ERα17p) identifies specific ERα‐isoform (ERα, ERα36)‐dependent and ‐independent actions in breast cancer cells",http://dx.doi.org/10.1016/j.molonc.2013.02.012,PMC5528475,,,"ERα17p is a peptide corresponding to the sequence P(295)LMIKRSKKNSLALSLT311 of the estrogen receptor alpha (ERα) and initially found to interfere with ERα‐related calmodulin binding. ERα17p was subsequently found to elicit estrogenic responses in E2‐deprived ERα‐positive breast cancer cells, increasing proliferation and ERE‐dependent gene transcription. Surprisingly, in E2‐supplemented media, ERα17p‐induced apoptosis and modified the actin network, influencing cell motility. Here, we report that ERα17p internalizes in breast cancer cells (T47D, MDA‐MB‐231, SKBR3) and induces a massive early (3 h) transcriptional activity. Remarkably, about 75% of significantly modified transcripts were also modified by E2, confirming the pro‐estrogenic profile of ERα17p. The different ER spectra of the used cell lines allowed us to identify a specific ERα17p signature related to ERα as well as its variant ERα36. With respect to ERα, the peptide activates nuclear (cell cycle, cell proliferation, nucleic acid and protein synthesis) and extranuclear signaling pathways. In contrast, through ERα36, it mainly triggers inhibitory actions on inflammation. This is the first work reporting a detailed ERα36‐specific transcriptional signature. In addition, we report that ERα17p‐induced transcripts related to apoptosis and actin modifying effects of the peptide are independent from its estrogen receptor(s)‐related actions. We discuss our findings in view of the potential use of ERα17p as a selective peptidomimetic estrogen receptor modulator (PERM).",,"['Notas, George', 'Kampa, Marilena', 'Pelekanou, Vassiliki', 'Troullinaki, Maria', 'Jacquot, Yves', 'Leclercq, Guy', 'Castanas, Elias']",,,,
,PMC,Evaluation of the FilmArray(®) Respiratory Panel for Clinical Use in a Large Children's Hospital,http://dx.doi.org/10.1002/jcla.21576,PMC6807554,,,"BACKGROUND: Respiratory pathogens are a leading cause of hospital admission and traditional detection methods are time consuming and insensitive. Multiplex molecular detection methods have recently been investigated in hope of replacing these traditional techniques with rapid panel‐based testing. OBJECTIVES: This study evaluated the FilmArray(®) Respiratory Panel ([FARP], Idaho Technology Inc., Salt Lake City, UT) as a replacement for direct fluorescent antibody (DFA) testing in a pediatric hospital. METHODS: Eleven of the 21 FARP analytes (Adenovirus, Bordetella pertussis, human Metapneumovirus, Influenza A, Influenza A H1N1 2009, Influenza B, Parainfluenza [1, 2, & 3], Respiratory Syncytial Virus, and rhinovirus) were evaluated using nasopharyngeal specimens. Positive samples were pooled in groups of 5. Samples identified by reference methods as positive for respiratory pathogens were used for the majority of positive samples. DFA was the reference method for ten analytes; Luminex(TM) xTAG Respiratory Virus Panel (RVP) was the reference method for rhinovirus. Discrepant results were resolved by positive culture and fluorescent antibody stain and/or laboratory‐developed real‐time polymerase chain reaction (PCR) assays (LDT). RESULTS: The agreement for most analytes was in concordance with the established reference methods with the exception of Adenovirus. Additionally, the FARP detected several pathogens not previously detected by DFA, and most were confirmed by LDT. Several DFA‐positive analytes were confirmed as true‐negatives by the FARP and LDT. CONCLUSION: FARP overall performed better than DFA with the exception of Adenovirus, making the FARP an attractive alternative to laboratories looking to replace DFA with a rapid, user‐friendly, multiplex molecular assay. J. Clin. Lab. Anal. 27:148–154, 2013. © 2013 Wiley Periodicals, Inc.",,"['Couturier, Marc Roger', 'Barney, Trenda', 'Alger, Garrison', 'Hymas, Weston C.', 'Stevenson, Jeffery B.', 'Hillyard, David', 'Daly, Judy A.']",,,,
,PMC,New Centromere Autoantigens Identified in Systemic Sclerosis Using Centromere Protein Microarrays,http://dx.doi.org/10.3899/jrheum.120264,PMC3962773,,,"OBJECTIVE: To identify novel centromere protein (CENP) targets of anticentromere antibodies (ACA), and to investigate their association with clinical manifestations of systemic sclerosis (SSc). METHODS: A CENP-focused protein microarray was fabricated by spotting 14 purified CENP. These microarrays were individually incubated with 35 ACA-positive SSc sera and 20 ACA-negative healthy control samples. Newly identified CENP autoantigens with high sensitivities were selected for validation and characterization. RESULTS: Statistical analysis revealed 11 CENP are potential target antigens of ACA in patients with SSc. Of them, 5 [CENP-P, CENP-Q, CENP-M (isoform I), CENP-J, and CENP-T] are novel, among which CENP-P and CENP-Q showed high sensitivities in ACA-positive SSc sera of 34.3% and 28.6%, respectively. Subsequently, 186 SSc sera (35 ACA-positives and 151 negatives), 69 ACA-positive sera from other various autoimmune diseases (primary Sjögren syndrome, systemic lupus erythematosus, rheumatoid arthritis, and primary biliary cirrhosis), and 31 healthy sera were assayed for the presence of anti-CENP-P and -Q autoantibodies by ELISA followed by Western blotting analysis. CENP-P and -Q autoantibodies were detected in ACA-positive sera of various disease groups; among them, SSc showed the highest detection rate. Anti-CENP-P was also found in 9 of the 151 ACA-negative sera. Analyses of the correlation with clinical information showed anti-CENP-P-positive patients had higher levels of IgG, IgA, and erythrocyte sedimentation rate among the ACA-positive cohort and were more vulnerable to renal disease in the ACA-negative patients with SSc. Regardless of ACA status, anti-CENP-P or Q-negative patients seem to be predominantly affected by interstitial lung disease. CONCLUSION: CENP-P and CENP-Q were identified as novel ACA autoantigens by CENP microarray assays followed by validation of ELISA and Western blotting. Both of them have prognostic utility for interstitial lung disease. CENP-P was associated with renal disease in an ACA-negative cohort.",,"['Song, Guang', 'Hu, Chaojun', 'Zhu, Heng', 'Wang, Li', 'Zhang, Fengchun', 'Li, Yongzhe', 'Wu, Lin']",,,,
,PMC,"NeST, a long noncoding RNA, controls microbial susceptibility and epigenetic activation of the Ifng locus",http://dx.doi.org/10.1016/j.cell.2013.01.015,PMC3577098,,,"Long noncoding RNAs (lncRNAs) are increasingly appreciated as regulators of cell-specific gene expression. Here, an enhancer-like lncRNA termed NeST (Nettoie Salmonella pas Theiler’s; cleanup Salmonella not Theiler’s) is shown to be causal for all phenotypes conferred by murine viral susceptibility locus Tmevp3. This locus was defined by crosses between SJL/J and B10.S mice and contains several candidate genes, including NeST. The SJL/J-derived locus confers higher lncRNA expression, increased interferon-γ abundance in activated CD8(+) T cells, increased Theiler’s virus persistence and decreased Salmonella enterica pathogenesis. Transgenic expression of NeST lncRNA alone was sufficient to confer all phenotypes of the SJL/J locus. NeST RNA was found to bind WDR5, a component of the histone H3 lysine 4 methytransferase complex, and to alter histone 3 methylation at the interferon gamma locus. Thus, this lncRNA regulates epigenetic marking of IFNγ-encoding chromatin, expression of IFN-γ and susceptibility to a viral and a bacterial pathogen.",,"['Gomez, J. Antonio', 'Wapinski, Orly L.', 'Yang, Yul W.', 'Bureau, Jean-François', 'Gopinath, Smita', 'Monack, Denise M.', 'Chang, Howard Y.', 'Brahic, Michel', 'Kirkegaard, Karla']",,,,
,PMC,"Advances in Microfluidic Materials, Functions, Integration and Applications",http://dx.doi.org/10.1021/cr300337x,PMC3624029,,,,,"['Nge, Pamela N.', 'Rogers, Chad I.', 'Woolley, Adam T.']",,,,
,PMC,Clinical characteristics and outcomes of influenza and other influenza-like illnesses in Mexico City,http://dx.doi.org/10.1016/j.ijid.2013.01.006,PMC3655081,,,"BACKGROUND: Influenza-like illnesses (ILI) are estimated to cause millions of deaths annually. Despite this disease burden, the etiologic causes of ILI are poorly described for many geographical regions. METHODS: Beginning in April 2010, we conducted an observational cohort study at five hospitals in Mexico City, enrolling subjects who met the criteria for ILI. Evaluations were conducted at enrollment and on day 28, with the collection of clinical data and a nasopharyngeal swab (or nasal aspirate in children). Swabs were tested by multiplex PCR for 15 viral pathogens and real-time PCR for influenza. RESULTS: During the first year, 1065 subjects were enrolled in this study, 55% of whom were hospitalized; 24% of all subjects were children. One or more pathogens were detected by PCR in 64% of subjects, most commonly rhinovirus (25% of all isolates) and influenza (24% of isolates). Six percent of subjects died, and of those, 54% had no pathogen identified. Rhinovirus was the most common pathogen among those who died, although it did not have the highest case fatality rate. CONCLUSIONS: Multiple respiratory viruses beyond influenza are associated with significant morbidity and mortality among adults and children in Mexico City. Detection of these agents could be useful for the adjustment of antibiotic treatment in severe cases.",,"['Galindo-Fraga, Arturo', 'Ortiz-Hernández, Ana A.', 'Ramírez-Venegas, Alejandra', 'Vázquez, Rafael Valdez', 'Moreno-Espinosa, Sarbelio', 'Llamosas-Gallardo, Beatriz', 'Pérez-Patrigeon, Santiago', 'Salinger, Maggie', 'Freimanis, Laura', 'Huang, Chiung-yu', 'Gu, Wenjuan', 'Guerrero, M. Lourdes', 'Beigel, John', 'Ruiz-Palacios, Guillermo M.']",,,,
,PMC,Interferon-induced ISG15 pathway: an ongoing virus–host battle,http://dx.doi.org/10.1016/j.tim.2013.01.005,PMC3622817,,,"ISG15 is an interferon-induced ubiquitin-like protein that is conjugated to target proteins via the sequential action of three enzymes that are also induced by interferon. Unlike ubiquitin, which is highly conserved, the sequence of ISG15 varies between species. ISG15 conjugation inhibits many viruses, and free (unconjugated) ISG15 can also act as an antiviral protein. Here we focus on the antiviral role of ISG15 conjugation and on countermeasures employed by several viruses. The countermeasure by influenza B virus is unique in that it exhibits species-specificity. Only the antiviral activity of human and non-human primate ISG15s can be blocked, providing one possible explanation for the restriction of influenza B virus to humans.",,"['Zhao, Chen', 'Collins, Mark', 'Hsiang, Tien-Ying', 'Krug, Robert M.']",,,,
,PMC,"Assessment of the effect of TLR7/8, TLR9 agonists and CD40 ligand on the transformation efficiency of Epstein-Barr virus in human B lymphocytes by limiting dilution assay",http://dx.doi.org/10.1007/s10616-013-9542-x,PMC3886530,,,"Infection of human B cells with Epstein-Barr virus (EBV) induces polyclonal activation in almost all infected cells, but a small proportion of infected cells are transformed to immortalized lymphoblastoid cell lines. Since B cells are activated also by CD40 ligand (CD40L) and Toll-like receptor (TLR) agonists via a similar signaling pathway, it is likely that costimulation through these molecules could result in synergistic enhancement of the transformation efficiency of EBV. In this study, the stimulatory effect of TLR7/8 (R848), TLR9 (CpG) agonists and/or CD40L on transformation efficiency of EBV in normal human B cells was assessed using the limiting dilution assay. Costimulation of peripheral blood mononuclear cells (PBMCs) with CpG and R848, but not CD40L, increased significantly the frequency of EBV transformed B cells (p < 0.001). Neither synergistic nor additive effects were observed between TLR agonists and CD40L and also TLR7/8 and TLR9 agonists. Costimulation with R848, CpG and CD40L enhanced the proliferative response of B cells infected with EBV. This effect was more evident when enriched B cells were employed, compared to PBMCs. The promoting effect of TLR agonists stimulation, implies that EBV may take advantage of the genes induced by the TLR stimulation pathway for viral latency and oncogenesis.",,"['Younesi, Vahid', 'Shirazi, Forough Golsaz', 'Memarian, Ali', 'Amanzadeh, Amir', 'Jeddi-Tehrani, Mahmood', 'Shokri, Fazel']",,,,
,PMC,Anti-IFNγ and peptide-tolerization therapies inhibit acute lung injury induced by crossreactive influenza-A (IAV)-specific memory T-cells,http://dx.doi.org/10.4049/jimmunol.1201936,PMC3594402,,,"Viral infections have variable outcomes with severe disease occurring in only few individuals. We hypothesized that this variable outcome could correlate with the nature of responses made to previous microbes. To test this, mice were infected initially with IAV and in memory-phase challenged with LCMV, which we show here to have relatively minor cross-reactivity with IAV. The outcome in genetically identical mice varied from mild pneumonitis to severe acute lung injury with extensive pneumonia and bronchiolization, similar to that observed in patients that died of the 1918 H1N1 pandemic. Lesion expression did not correlate with virus titers. Instead, disease severity directly correlated with and was predicted by the frequency of IAV-PB1(703)- and -PA(224)-specific responses, which crossreacted with LCMV-GP(34) and -GP(276), respectively. Eradication or functional ablation of these pathogenic memory T-cell populations, using mutant-viral strains, peptide-based tolerization strategies, or short-term anti-IFNγ treatment inhibited severe lesions such as bronchiolization from occurring. Heterologous immunity can shape outcome of infections and likely individual responses to vaccination, and can be manipulated to treat or prevent severe pathology.",,"['Wlodarczyk, Myriam F.', 'Kraft, Anke R.', 'Chen, Hong D.', 'Kenney, Laurie L.', 'Selin, Liisa K.']",,,,
,PMC,Generalized dermatitis associated with Malassezia overgrowth in cats: A report of six cases in France,http://dx.doi.org/10.1016/j.mmcr.2013.01.005,PMC3885935,,,"We recently observed six cases of generalized dermatitis associated with Malassezia overgrowth in cats presented to the Veterinary College of Alfort, France. Elevated numbers of yeasts were observed in lesional skin by cytology and culture. Skin lesions occurred on the face, ventral neck, abdomen and ear canals and were characterized by some degree of alopecia, erythema and crusting. In most cases, pruritus was intense. The species M. pachydermatis was systematically isolated.",,"['Crosaz, Odile', 'Legras, Audrey', 'Vilaplana-Grosso, Federico', 'Debeaupuits, Julien', 'Chermette, René', 'Hubert, Blaise', 'Guillot, Jacques']",,,,
,PMC,Lentiviral Delivery of RNAi for In Vivo Lineage-Specific Modulation of Gene Expression in Mouse Lung Macrophages,http://dx.doi.org/10.1038/mt.2013.19,PMC3616534,,,"Although RNA interference (RNAi) has become a ubiquitous laboratory tool since its discovery 12 years ago, in vivo delivery to selected cell types remains a major technical challenge. Here, we report the use of lentiviral vectors for long-term in vivo delivery of RNAi selectively to resident alveolar macrophages (AMs), key immune effector cells in the lung. We demonstrate the therapeutic potential of this approach by RNAi-based downregulation of p65 (RelA), a component of the pro-inflammatory transcriptional regulator, nuclear factor κB (NF-κB) and a key participant in lung disease pathogenesis. In vivo RNAi delivery results in decreased induction of NF-κB and downstream neutrophilic chemokines in transduced AMs as well as attenuated lung neutrophilia following stimulation with lipopolysaccharide (LPS). Through concurrent delivery of a novel lentiviral reporter vector (lenti-NF-κB-luc-GFP) we track in vivo expression of NF-κB target genes in real time, a critical step towards extending RNAi-based therapy to longstanding lung diseases. Application of this system reveals that resident AMs persist in the airspaces of mice following the resolution of LPS-induced inflammation, thus allowing these localized cells to be used as effective vehicles for prolonged RNAi delivery in disease settings.",,"['Wilson, Andrew A', 'Kwok, Letty W', 'Porter, Emily L', 'Payne, Julie G', 'McElroy, Gregory S', 'Ohle, Sarah J', 'Greenhill, Sara R', 'Blahna, Matthew T', 'Yamamoto, Kazuko', 'Jean, Jyh C', 'Mizgerd, Joseph P', 'Kotton, Darrell N']",,,,
,PMC,Deubiquitinase function of arterivirus papain-like protease 2 suppresses the innate immune response in infected host cells,http://dx.doi.org/10.1073/pnas.1218464110,PMC3587229,,,"Protein ubiquitination regulates important innate immune responses. The discovery of viruses encoding deubiquitinating enzymes (DUBs) suggests they remove ubiquitin to evade ubiquitin-dependent antiviral responses; however, this has never been conclusively demonstrated in virus-infected cells. Arteriviruses are economically important positive-stranded RNA viruses that encode an ovarian tumor (OTU) domain DUB known as papain-like protease 2 (PLP2). This enzyme is essential for arterivirus replication by cleaving a site within the viral replicase polyproteins and also removes ubiquitin from cellular proteins. To dissect this dual specificity, which relies on a single catalytic site, we determined the crystal structure of equine arteritis virus PLP2 in complex with ubiquitin (1.45 Å). PLP2 binds ubiquitin using a zinc finger that is uniquely integrated into an exceptionally compact OTU-domain fold that represents a new subclass of zinc-dependent OTU DUBs. Notably, the ubiquitin-binding surface is distant from the catalytic site, which allowed us to mutate this surface to significantly reduce DUB activity without affecting polyprotein cleavage. Viruses harboring such mutations exhibited WT replication kinetics, confirming that PLP2-mediated polyprotein cleavage was intact, but the loss of DUB activity strikingly enhanced innate immune signaling. Compared with WT virus infection, IFN-β mRNA levels in equine cells infected with PLP2 mutants were increased by nearly an order of magnitude. Our findings not only establish PLP2 DUB activity as a critical factor in arteriviral innate immune evasion, but the selective inactivation of DUB activity also opens unique possibilities for developing improved live attenuated vaccines against arteriviruses and other viruses encoding similar dual-specificity proteases.",,"['van Kasteren, Puck B.', 'Bailey-Elkin, Ben A.', 'James, Terrence W.', 'Ninaber, Dennis K.', 'Beugeling, Corrine', 'Khajehpour, Mazdak', 'Snijder, Eric J.', 'Mark, Brian L.', 'Kikkert, Marjolein']",,,,
,PMC,Microsimulation of Financial Impact of Demand Surge on Hospitals: The H1N1 Influenza Pandemic of Fall 2009,http://dx.doi.org/10.1111/1475-6773.12041,PMC3626336,,,"OBJECTIVE: Microsimulation was used to assess the financial impact on hospitals of a surge in influenza admissions in advance of the H1N1 pandemic in the fall of 2009. The goal was to estimate net income and losses (nationally, and by hospital type) of a response of filling unused hospital bed capacity proportionately and postponing elective admissions (a “passive” supply response). METHODS: Epidemiologic assumptions were combined with assumptions from other literature (e.g., staff absenteeism, profitability by payer class), Census data on age groups by region, and baseline hospital utilization data. Hospital discharge records were available from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS). Hospital bed capacity and staffing were measured with the American Hospital Association's (AHA) Annual Survey. RESULTS: Nationwide, in a scenario of relatively severe epidemiologic assumptions, we estimated aggregate net income of $119 million for about 1 million additional influenza-related admissions, and a net loss of $37 million for 52,000 postponed elective admissions. IMPLICATIONS: Aggregate and distributional results did not suggest that a policy of promising additional financial compensation to hospitals in anticipation of the surge in flu cases was necessary. The analysis identified needs for better information of several types to improve simulations of hospital behavior and impacts during demand surges.",,"['Braithwaite, Sabina', 'Friedman, Bernard', 'Mutter, Ryan', 'Handrigan, Michael']",,,,
,PMC,Animal models for highly pathogenic emerging viruses,http://dx.doi.org/10.1016/j.coviro.2013.01.001,PMC3644300,,,"Exotic and emerging viral pathogens associated with high morbidity and mortality in humans are being identified annually with recent examples including Lujo virus in southern Africa, Severe fever with Thrombocytopenia virus in China and a SARS-like coronavirus in the Middle East. The sporadic nature of these infections hampers our understanding of these diseases and limits the opportunities to design appropriate medical countermeasures against them. Due to this, animal models are utilized to gain insight into the pathogenesis of disease with the overall goal of identifying potential targets for intervention and evaluating specific therapeutics and vaccines. For these reasons it is imperative that animal models of disease recapitulate the human condition as closely as possible in order to provide the best predictive data with respect to the potential efficacy in humans. In this article we review the current status of disease models for highly pathogenic and emerging viral pathogens.",,"['Safronetz, David', 'Geisbert, Thomas W.', 'Feldmann, Heinz']",,,,
,PMC,Identification of Viral Pathogen Diversity in Sewage Sludge by Metagenome Analysis,http://dx.doi.org/10.1021/es305181x,PMC3963146,,,"The large diversity of viruses that exist in human populations are potentially excreted into sewage collection systems and concentrated in sewage sludge. In the US, the primary fate of processed sewage sludge (class B biosolids) is application to agricultural land as a soil amendment. To characterize and understand infectious risks associated with land application, and to describe the diversity of viruses in human populations, shotgun viral metagenomics was applied to 10 sewage sludge samples from 5 wastewater treatment plants throughout the continental U.S, each serving between 100,000 and 1,000,000 people. Nearly 330 million DNA sequences were produced and assembled, and annotation resulted in identifying 43 (26 DNA, 17 RNA) different types of human viruses in sewage sludge. Novel insights include the high abundance of newly emerging viruses (e.g. Coronavirus HKU1, Klassevirus, and Cosavirus) the strong representation of respiratory viruses, and the relatively minor abundance and occurrence of Enteroviruses. Viral metagenome sequence annotations were reproducible and independent PCR-based identification of selected viruses suggests that viral metagenomes were a conservative estimate of the true viral occurrence and diversity. These results represent the most complete description of human virus diversity in any wastewater sample to date, provide engineers and environmental scientists with critical information on important viral agents and routes of infection from exposure to wastewater and sewage sludge, and represent a significant leap forward in understanding the pathogen content of class B biosolids.",,"['BIBBY, KYLE', 'PECCIA, JORDAN']",,,,
,PMC,Respiratory Virus Shedding in a Cohort of On-Duty Healthcare Workers Undergoing Prospective Surveillance,http://dx.doi.org/10.1086/669857,PMC3730277,,,"BACKGROUND: Healthcare-associated transmission of respiratory viruses is a concerning patient safety issue. DESIGN: Surveillance for influenza virus among a cohort of healthcare workers (HCWs) was conducted in a tertiary care children’s hospital from November 2009 until April 2010, using biweekly nasal swab collection. If a subject reported respiratory symptoms, an additional specimen was collected. Specimens from ill HCWs and a randomly selected sample from asymptomatic subjects were tested for additional respiratory viruses by multiplex PCR. RESULTS: From 170 enrolled subjects, 1404 nasal swabs were collected. Influenza circulated at very low levels during the surveillance period and 74.2% of subjects received influenza vaccination. Influenza was not detected in any specimen. Multiplex respiratory virus PCR analysis of all 119 samples from symptomatic subjects and 200 specimens from asymptomatic subjects yielded a total of 42 positive specimens; 7 (16.7%) in asymptomatic subjects. Viral shedding was associated with report of any symptom (OR 13.06, p<0.0001, 95% CI 5.45-31.28) and younger age (OR 0.96, p=0.023, 95% CI 0.92-0.99) when controlled for gender and occupation of physician or nurse. After the surveillance period, 46% of subjects reported working while ill with an influenza-like illness during the previous influenza season. CONCLUSIONS: In this cohort, HCWs working while ill was common, as was viral shedding among those with symptoms. Asymptomatic viral shedding was infrequent, but did occur. HCWs should refrain from patient care duties while ill, and staffing contingencies should accommodate them.",,"['Esbenshade, Jennifer C.', 'Edwards, Kathryn M.', 'Esbenshade, Adam J.', 'Rodriguez, Vanessa E.', 'Talbot, H. Keipp', 'Joseph, Marlon F.', 'Nwosu, Samuel K.', 'Chappell, James D.', 'Gern, James E.', 'Williams, John V.', 'Talbot, Thomas R.']",,,,
,PMC,Live Cell Imaging of Viral Entry,http://dx.doi.org/10.1016/j.coviro.2013.01.005,PMC3587724,,,"Viral entry encompasses the initial steps of infection starting from virion host cell attachment to viral genome release. Given the dynamic interactions between the virus and the host, many questions related to viral entry can be directly addressed by live cell imaging. Recent advances in fluorescent labeling of viral and cellular components, fluorescence microscopy with high sensitivity and spatiotemporal resolution, and image analysis enabled studies of a broad spectrum across many viral entry steps, including virus-receptor interactions, internalization, intracellular transport, genomic release, nuclear transport, and cell-to-cell transmission. Collectively, these live cell imaging studies have not only enriched our understandings of the viral entry mechanisms, but also provided novel insights into basic cellular biology processes.",,"['Sun, Eileen', 'He, Jiang', 'Zhuang, Xiaowei']",,,,
,PMC,Establishing a Liquid-covered Culture of Polarized Human Airway Epithelial Calu-3 Cells to Study Host Cell Response to Respiratory Pathogens In vitro,http://dx.doi.org/10.3791/50157,PMC3600762,,,"The apical and basolateral surfaces of airway epithelial cells demonstrate directional responses to pathogen exposure in vivo. Thus, ideal in vitro models for examining cellular responses to respiratory pathogens polarize, forming apical and basolateral surfaces. One such model is differentiated normal human bronchial epithelial cells (NHBE). However, this system requires lung tissue samples, expertise isolating and culturing epithelial cells from tissue, and time to generate an air-liquid interface culture. Calu-3 cells, derived from a human bronchial adenocarcinoma, are an alternative model for examining the response of proximal airway epithelial cells to respiratory insult(1), pharmacological compounds(2-6), and bacterial(7-9) and viral pathogens, including influenza virus, rhinovirus and severe acute respiratory syndrome - associated coronavirus(10-14). Recently, we demonstrated that Calu-3 cells are susceptible to respiratory syncytial virus (RSV) infection in a manner consistent with NHBE(15,16) . Here, we detail the establishment of a polarized, liquid-covered culture (LCC) of Calu-3 cells, focusing on the technical details of growing and culturing Calu-3 cells, maintaining cells that have been cultured into LCC, and we present the method for performing respiratory virus infection of polarized Calu-3 cells. To consistently obtain polarized Calu-3 LCC, Calu-3 cells must be carefully subcultured before culturing in Transwell inserts. Calu-3 monolayer cultures should remain below 90% confluence, should be subcultured fewer than 10 times from frozen stock, and should regularly be supplied with fresh medium. Once cultured in Transwells, Calu-3 LCC must be handled with care. Irregular media changes and mechanical or physical disruption of the cell layers or plates negatively impact polarization for several hours or days. Polarization is monitored by evaluating trans-epithelial electrical resistance (TEER) and is verified by evaluating the passive equilibration of sodium fluorescein between the apical and basolateral compartments(17,18) . Once TEER plateaus at or above 1,000 Ω×cm(2), Calu-3 LCC are ready to use to examine cellular responses to respiratory pathogens.",,"['Harcourt, Jennifer L.', 'Haynes, Lia M.']",,,,
,PMC,Local expression of interleukin‐2 by B16 melanoma cells results in decreased tumour growth and long‐term tumour dormancy,http://dx.doi.org/10.1111/imm.12037,PMC3573281,,,"The tumour microenvironment is complex containing not only neoplastic cells but also a variety of host cells. The heterogeneous infiltrating immune cells include subsets of cells with opposing functions, whose activities are mediated either directly or through the cytokines they produce. Systemic delivery of cytokines such as interleukin‐2 ( IL‐2) has been used clinically to enhance anti‐tumour responses, but these molecules are generally thought to have evolved to act locally in a paracrine fashion. In this study we examined the effect of local production of IL‐2 on the growth and the immune response to B16 melanoma cells. We found that the local production of IL‐2 enhances the number of interferon‐γ‐expressing CD8 T and natural killer cells in the tumour, as well as inducing expression of vascular cell adhesion molecule 1 on tumour vessels. These responses were largely absent in interferon‐γ knockout mice. The expression of IL‐2 in the tumour microenvironment decreases tumour growth despite also enhancing Foxp3(+) CD4(+) regulatory T cells and anti‐inflammatory cytokines such as IL‐10. Higher levels of IL‐2 in the tumour microenvironment eliminated the progressive growth of the B16 cells in vivo, and this inhibition was dependent on the presence of either T cells or, to a lesser extent, natural killer cells. Surprisingly however, the B16 tumours were not completely eliminated but instead were controlled for an extended period of time, suggesting that a form of tumour dormancy was established.",,"['Gerber, Scott A.', 'Sorensen, Elizabeth W.', 'Sedlacek, Abigail L.', 'Lim, Joanne Y. H.', 'Skrombolas, Denise', 'Frelinger, John G.', 'Lord, Edith M.']",,,,
,PMC,Recent advances in understanding viral evasion of type I interferon,http://dx.doi.org/10.1111/imm.12038,PMC3573272,,,"The type I interferon (IFN) system mediates a wide variety of antiviral effects and represents an important first barrier to virus infection. Consequently, viruses have developed an impressive diversity of tactics to circumvent IFN responses. Evasion strategies can involve preventing initial virus detection, via the disruption of the Toll‐like receptors or the retinoic acid inducible gene I (RIG‐I) ‐like receptors, or by avoiding the initial production of the ligands recognized by these receptors. An alternative approach is to preclude IFN production by disarming or degrading the transcription factors involved in the expression of IFN, such as interferon regulatory factor 3 (IRF3)/IRF7, nuclear factor‐κB (NF‐κB), or ATF‐2/c‐jun, or by inducing a general block on host cell transcription. Viruses also oppose IFN signalling, both by disturbing the type I IFN receptor and by impeding JAK/STAT signal transduction upon IFN receptor engagement. In addition, the global expression of IFN‐stimulated genes (ISGs) can be obstructed via interference with epigenetic signalling, and specific ISGs can also be selectively targeted for inhibition. Finally, some viruses disrupt IFN responses by co‐opting negative regulatory systems, whereas others use antiviral mechanisms to their own advantage. Here, we review recent developments in this field.",,"['Taylor, Kathryne E.', 'Mossman, Karen L.']",,,,
,PMC,Enhanced Intrapulmonary Delivery of Anticancer siRNA for Lung Cancer Therapy Using Cationic Ethylphosphocholine-based Nanolipoplexes,http://dx.doi.org/10.1038/mt.2013.10,PMC3616525,,,"Here, we report a cationic nanolipoplex as a pulmonary cellular delivery system for small-interfering RNA (siRNA). Six nanoliposomes differing in cationic lipids were formulated and screened in vitro and in vivo for cellular delivery functions in lung cells/tissues. Although the six nanoliposomes showed similar siRNA delivery efficiency in vitro, they exhibited significant differences in pulmonary cellular delivery functions in vivo. Among the various nanoliposomes, cationic dioleoyl-sn-glycero-3-ethylphosphocholine and cholesterol (ECL)-based nanoliposomes showed the highest pulmonary cellular delivery in vivo and the lowest cytotoxicity in vitro. The delivery efficiency of fluorescent siRNA in ECL nanoliposomes was 26.2-fold higher than that of naked siRNA in vivo. Treatment with Mcl1 (myeloid cell leukemia sequence 1)-specific siRNA (siMcl1) using ECL nanolipoplexes reduced target expression in B16F10 cell lines, whereas control, luciferase-specific siGL2 in ECL nanolipoplexes did not. In metastatic lung cancer mouse models induced by B16F10 or Lewis lung carcinoma (LLC) cells, intratracheal administration of siMcl1 in ECL nanolipoplexes significantly silenced Mcl1 mRNA and protein levels in lung tissue. Reduced formation of melanoma tumor nodules was observed in the lung. These results demonstrate the utility of ECL nanoliposomes for pulmonary delivery of therapeutic siRNA for the treatment of lung cancers and potentially for other respiratory diseases.",,"['Shim, Gayong', 'Choi, Hyun-woo', 'Lee, Sangbin', 'Choi, Junhyeok', 'Yu, Yong Hee', 'Park, Da-Eui', 'Choi, Yongseok', 'Kim, Chan-Wha', 'Oh, Yu-Kyoung']",,,,
,PMC,"Intrinsic evolutionary constraints on protease structure, enzyme acylation, and the identity of the catalytic triad",http://dx.doi.org/10.1073/pnas.1221050110,PMC3581919,,,"The study of proteolysis lies at the heart of our understanding of biocatalysis, enzyme evolution, and drug development. To understand the degree of natural variation in protease active sites, we systematically evaluated simple active site features from all serine, cysteine and threonine proteases of independent lineage. This convergent evolutionary analysis revealed several interrelated and previously unrecognized relationships. The reactive rotamer of the nucleophile determines which neighboring amide can be used in the local oxyanion hole. Each rotamer–oxyanion hole combination limits the location of the moiety facilitating proton transfer and, combined together, fixes the stereochemistry of catalysis. All proteases that use an acyl-enzyme mechanism naturally divide into two classes according to which face of the peptide substrate is attacked during catalysis. We show that each class is subject to unique structural constraints that have governed the convergent evolution of enzyme structure. Using this framework, we show that the γ-methyl of Thr causes an intrinsic steric clash that precludes its use as the nucleophile in the traditional catalytic triad. This constraint is released upon autoproteolysis and we propose a molecular basis for the increased enzymatic efficiency introduced by the γ-methyl of Thr. Finally, we identify several classes of natural products whose mode of action is sensitive to the division according to the face of attack identified here. This analysis of protease structure and function unifies 50 y of biocatalysis research, providing a framework for the continued study of enzyme evolution and the development of inhibitors with increased selectivity.",,"['Buller, Andrew R.', 'Townsend, Craig A.']",,,,
,PMC,ERK signaling is triggered by hepatitis C virus E2 protein through DC-SIGN,http://dx.doi.org/10.1007/s12192-013-0405-3,PMC3682013,,,"Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is a binding receptor for hepatitis C virus (HCV). Binding of HCV envelope protein E2 to target cells is a prerequisite to DC-SIGN-mediated signaling. Using cell lines with stable or transient expression of DC-SIGN, we investigated effects of soluble HCV E2 protein on ERK pathway. MEK and ERK are activated by the E2 in NIH3T3 cells stably expressing DC-SIGN. Treatment of the cells with antibody to DC-SIGN results in inhibition of the E2 binding as well as the E2-induced MEK and ERK activation. In HEK293T cells transiently expressing DC-SIGN, activation of MEK and ERK is also induced by the E2. Activation of ERK pathway by HCV E2 through DC-SIGN provides useful information for understanding cellular receptor-mediated signaling.",,"['Zhao, Lan-Juan', 'Wang, Wen', 'Ren, Hao', 'Qi, Zhong-Tian']",,,,
,PMC,Reducing HIV-Related Stigma in Health Care Settings: A Randomized Controlled Trial in China,http://dx.doi.org/10.2105/AJPH.2012.300854,PMC3556241,,,"Objectives. The objective of the intervention was to reduce service providers’ stigmatizing attitudes and behaviors toward people living with HIV. Methods. The randomized controlled trial was conducted in 40 county-level hospitals in 2 provinces of China between October 2008 and February 2010. Forty-four service providers were randomly selected from each hospital, yielding a total of 1760 study participants. We randomized the hospitals to either an intervention condition or a control condition. In the intervention hospitals, about 15% of the popular opinion leaders were identified and trained to disseminate stigma reduction messages. Results. We observed significant improvements for the intervention group in reducing prejudicial attitudes (P < .001), reducing avoidance intent towards people living with HIV (P < .001), and increasing institutional support in the hospitals (P = .003) at 6 months after controlling for service providers’ background factors and clinic-level characteristics. The intervention effects were sustained and strengthened at 12 months. Conclusions. The intervention reduced stigmatizing attitudes and behaviors among service providers. It has the potential to be integrated into the health care systems in China and other countries.",,"['Li, Li', 'Wu, Zunyou', 'Liang, Li-Jung', 'Lin, Chunqing', 'Guan, Jihui', 'Jia, Manhong', 'Rou, Keming', 'Yan, Zhihua']",,,,
,PMC,Efficacy of Oral Ribavirin in Hematologic Disease Patients with Paramyxovirus Infection: Analytic Strategy Using Propensity Scores,http://dx.doi.org/10.1128/AAC.01961-12,PMC3553680,,,"Few antiviral agents are available for treating paramyxovirus infections, such as those involving respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV). We evaluated the effect of oral ribavirin on clinical outcomes of paramyxovirus infections in patients with hematological diseases. All adult patients with paramyxovirus were retrospectively reviewed over a 2-year period. Patients who received oral ribavirin were compared to those who received supportive care without ribavirin therapy. A propensity-matched case-control study and a logistic regression model with inverse probability of treatment weighting (IPTW) were performed to reduce the effect of selection bias in assignment for oral ribavirin therapy. A total of 145 patients, including 64 (44%) with PIV, 60 (41%) with RSV, and 21 (15%) with hMPV, were analyzed. Of these 145 patients, 114 (78%) received oral ribavirin and the remaining 31 (21%) constituted the nonribavirin group. Thirty-day mortality and underlying respiratory death rates were 31% (35/114) and 12% (14/114), respectively, for the oral ribavirin group versus 19% (6/31) and 16% (5/31), respectively, for the nonribavirin group (P = 0.21 and P = 0.56). In the case-control study, the 30-day mortality rate in the ribavirin group was 24% (5/21) versus 19% (4/21) in the nonribavirin group (P = 0.71). In addition, the logistic regression model with IPTW revealed no significant difference in 30-day mortality (adjusted hazard ratio of 1.3; 95% confidence interval [95% CI] of 0.3 to 5.8) between the two groups. Steroid use (adjusted odds ratio, 5.67; P = 0.01) and upper respiratory tract infection (adjusted odds ratio, 0.07; P = 0.001) was independently associated with mortality. Our data suggest that oral ribavirin therapy may not improve clinical outcomes in hematologic disease patients infected with paramyxovirus.",,"['Park, So-Youn', 'Baek, Seunghee', 'Lee, Sang-Oh', 'Choi, Sang-Ho', 'Kim, Yang Soo', 'Woo, Jun Hee', 'Sung, Heungsup', 'Kim, Mi-Na', 'Kim, Dae-Young', 'Lee, Jung-Hee', 'Lee, Je-Hwan', 'Lee, Kyoo-Hyung', 'Kim, Sung-Han']",,,,
,PMC,An autophagy-independent role for LC3 in equine arteritis virus replication,http://dx.doi.org/10.4161/auto.22743,PMC3552881,,,"Equine arteritis virus (EAV) is an enveloped, positive-strand RNA virus. Genome replication of EAV has been associated with modified intracellular membranes that are shaped into double-membrane vesicles (DMVs). We showed by immuno-electron microscopy that the DMVs induced in EAV-infected cells contain double-strand (ds)RNA molecules, presumed RNA replication intermediates, and are decorated with the autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3). Replication of EAV, however, was not affected in autophagy-deficient cells lacking autophagy-related protein 7 (ATG7). Nevertheless, colocalization of DMVs and LC3 was still observed in these knockout cells, which only contain the nonlipidated form of LC3. Although autophagy is not required, depletion of LC3 markedly reduced the replication of EAV. EAV replication could be fully restored in these cells by expression of a nonlipidated form of LC3. These findings demonstrate an autophagy-independent role for LC3 in EAV replication. Together with the observation that EAV-induced DMVs are also positive for ER degradation-enhancing α-mannosidase-like 1 (EDEM1), our data suggested that this virus, similarly to the distantly-related mouse hepatitis coronavirus, hijacks the ER-derived membranes of EDEMosomes to ensure its efficient replication.",,"['Monastyrska, Iryna', 'Ulasli, Mustafa', 'Rottier, Peter J.M.', 'Guan, Jun-Lin', 'Reggiori, Fulvio', 'de Haan, Cornelis A.M.']",,,,
,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.13.010213,PMC3605014,,,,,,,,,
,PMC,Aerosol-Generating Procedures and Risk of Transmission of Acute Respiratory Infections: A Systematic Review,,PMC3579388,,,,,"['Tran, K', 'Cimon, K', 'Severn, M', 'Pessoa-Silva, CL', 'Conly, J']",,,,
,PMC,Descriptive epidemiology of upper respiratory disease and associated risk factors in cats in an animal shelter in coastal western Canada,,PMC3552587,,,"We examined 250 cats at an animal shelter in the coastal temperate region of Canada to determine whether age, source, gender, and sterilization status influenced risk of shedding at intake, transmission of infection, and development of clinical upper respiratory disease (URD). On admission, 28% of the cats were positive for 1 or more infectious agent related to URD; 21% were carriers of Mycoplasma felis and < 3% were carriers of feline calicivirus (FCV), feline herpesvirus-1 (FHV-1) or Bordetella bronchiseptica. Chlamydophila felis and H1N1 influenza virus were not detected. Carrier status was not affected by source, gender, sterilization status, or age (P > 0.05). Viral and bacterial shedding increased by 9% and 11%, respectively, over 3 sampling times (days 1, 4, and 10). Over 40 days after admission, the cumulative probability of developing URD was 2.2 times greater for stray than owner-surrendered cats (P = 0.02) and 0.5 times as great for neutered cats as for intact cats (P = 0.03). Cats that were shedding at intake were 2.6 times more likely to develop URD than were non-carriers (P < 0.002). Cats with FHV-1 and B. bronchiseptica infections were most at risk compared with non-shedding cats (P < 0.01).",,"['Gourkow, Nadine', 'Lawson, James H.', 'Hamon, Sara C.', 'Phillips, Clive J.C.']",,,,
,PMC,Predicting ALI Resolution: A Role For Chest CT?,http://dx.doi.org/10.1097/CCM.0b013e3182741c12,PMC4673397,,,,,"['Files, D. Clark', 'Hite, R. Duncan']",,,,
,PMC,Identification of inhibitory scFv antibodies targeting fibroblast activation protein utilizing phage display functional screens,http://dx.doi.org/10.1096/fj.12-210377,PMC3545529,,,"Fibroblast activation protein (FAP) is a serine protease selectively expressed on tumor stromal fibroblasts in epithelial carcinomas and is important in cancer growth, adhesion, and metastases. As FAP enzymatic activity is a potent therapeutic target, we aimed to identify inhibitory antibodies. Using a competitive inhibition strategy, we used phage display techniques to identify 53 single-chain variable fragments (scFvs) after three rounds of panning against FAP. These scFvs were expressed and characterized for binding to FAP by surface plasmon resonance and flow cytometry. Functional assessment of these antibodies yielded an inhibitory scFv antibody, named E3, which could attenuate 35% of FAP cleavage of the fluorescent substrate Ala-Pro-7-amido-4-trifluoromethylcoumarin compared with nonfunctional scFv control. Furthermore, a mutant E3 scFv was identified by yeast affinity maturation. It had higher affinity (4-fold) and enhanced inhibitory effect on FAP enzyme activity (3-fold) than E3. The application of both inhibitory anti-FAP scFvs significantly affected the formation of 3-dimensional FAP-positive cell matrix, as demonstrated by reducing the fibronectin fiber orientation from 41.18% (negative antibody control) to 34.06% (E3) and 36.15% (mutant E3), respectively. Thus, we have identified and affinity-maturated the first scFv antibody capable of inhibiting FAP function. This scFv antibody has the potential to disrupt the role of FAP in tumor invasion and metastasis.—Zhang, J., Valianou, M., Simmons, H., Robinson, M. K., Lee, H.-O., Mullins, S. R., Marasco, W. A., Adams, G. P., Weiner, L. M., Cheng, J. D. Identification of inhibitory ScFv antibodies targeting fibroblast activation protein utilizing phage display functional screens.",,"['Zhang, Jiping', 'Valianou, Matthildi', 'Simmons, Heidi', 'Robinson, Matthew K.', 'Lee, Hyung-Ok', 'Mullins, Stefanie R.', 'Marasco, Wayne A.', 'Adams, Gregory P.', 'Weiner, Louis M.', 'Cheng, Jonathan D.']",,,,
,PMC,Factors shaping the adaptive landscape for arboviruses: implications for the emergence of disease,http://dx.doi.org/10.2217/fmb.12.139,PMC3621119,,,"Many examples of the emergence or re-emergence of infectious diseases involve the adaptation of zoonotic viruses to new amplification hosts or to humans themselves. These include several instances of simple mutational adaptations, often to hosts closely related to the natural reservoirs. However, based on theoretical grounds, arthropod-borne viruses, or arboviruses, may face several challenges for adaptation to new hosts. Here, we review recent findings regarding adaptive evolution of arboviruses and its impact on disease emergence. We focus on the zoonotic alphaviruses Venezuelan equine encephalitis and chikungunya viruses, which have undergone adaptive evolution that mediated recent outbreaks of disease, as well as the flaviviruses dengue and West Nile viruses, which have emerged via less dramatic adaptive mechanisms.",,"['Coffey, Lark L', 'Forrester, Naomi', 'Tsetsarkin, Konstantin', 'Vasilakis, Nikos', 'Weaver, Scott C']",,,,
,PMC,The diversity of human RNA viruses,http://dx.doi.org/10.2217/fvl.12.129,PMC5831953,,,"We still cannot answer the very basic question “how many kinds of RNA viruses are there?” even for those that infect humans. It is often suggested that there remains a large number of viruses in humans that we have not yet discovered or recognised, and that there is a much larger and rapidly evolving pool of potential new viruses in mammalian and avian reservoirs that humans are continually being exposed to. However, a careful examination of discovery rates of new human RNA virus species, genera and families challenges this view, raising the possibility that the diversity is much more limited. Moreover, there is some evidence that the cast of human viruses is dynamic, with existing viruses disappearing (at least from humans) and new viruses appearing (perhaps evolving) over timescales of decades. Most of these new viruses, however, remain rare; only a small (but highly significant) minority are capable of spreading extensively through human populations.",,"['Woolhouse, Mark E.J.', 'Adair, Kyle']",,,,
,PMC,Antigen replacement of domains D2 and D3 in flagellin promotes mucosal IgA production and attenuates flagellin-induced inflammatory response after intranasal immunization,http://dx.doi.org/10.4161/hv.23809,PMC3899144,,,"Targeting early infection in mucosal sites is one of the primary goals for mucosal vaccines so as to prevent pathogen mucosal transmission and infection. The TLR5 agonist flagellin was deemed to be a mucosal adjuvant candidate for clinical usage. However, the high antigenicity of flagellin and the possible inflammatory injury induced by flagellin might restrict its clinical usage. Here HIV-1 p24 protein was selected as an antigen model and we replaced the main antigenicity region domains D2 and D3 of non-pathogenic E.coli-derived flagellin (KF). The derived soluble protein KFD-p24 3D was then compared with KF-p24, which fused p24 directly to the C-terminal of KF. In vitro and ex vivo experiments showed that KFD-p24 3D has lower TLR5 agonist efficacy and less immunocyte-activating efficacy. Interestingly, the production of KF- specific antibody was highly reduced, and KFD-p24 3D induced IgA-biased antibody responses in mucosal sites. Moreover, KFD-p24 3D induced far fewer systemic inflammatory responses and abrogated detectable inflammatory side effects on mice, even at the high dose. The properties of enhanced IgA generation and attenuated inflammatory responses broaden the safe-dose range of KFD-p24 3D flagellin, creating a potentially promising mucosal adjuvant.",,"['Yang, Jingyi', 'Zhong, Maohua', 'Zhang, Yan', 'Zhang, Ejuan', 'Sun, Ying', 'Cao, Yuan', 'Li, Yaoming', 'Zhou, Dihan', 'He, Benxia', 'Chen, Yaoqing', 'Yang, Yi', 'Yu, Jie', 'Yan, Huimin']",,,,
,PMC,Felid Herpesvirus 1 as a Causative Agent of Severe Nonsuppurative Meningoencephalitis in a Domestic Cat,http://dx.doi.org/10.1128/JCM.02462-12,PMC3553892,,,Felid herpesvirus 1 is an important respiratory pathogen of domestic cats. This report presents the first case of severe nonsuppurative meningoencephalitis caused by this virus in a cat.,,"['Hora, Aline S.', 'Tonietti, Paloma O.', 'Guerra, Juliana M.', 'Leme, Maiara C.', 'Pena, Hilda F. J.', 'Maiorka, Paulo C.', 'Brandão, Paulo E.']",,,,
,PMC,Identification and Structural Characterization of a Broadly Neutralizing Antibody Targeting a Novel Conserved Epitope on the Influenza Virus H5N1 Hemagglutinin,http://dx.doi.org/10.1128/JVI.02344-12,PMC3571485,,,"The unabated circulation of the highly pathogenic avian influenza A virus/H5N1 continues to be a serious threat to public health worldwide. Because of the high frequency of naturally occurring mutations, the emergence of H5N1 variants with high virulence has raised great concerns about the potential transmissibility of the virus in humans. Recent studies have shown that laboratory-mutated or reassortant H5N1 viruses could be efficiently transmitted among mammals, particularly ferrets, the best animal model for humans. Thus, it is critical to establish effective strategies to combat future H5N1 pandemics. In this study, we identified a broadly neutralizing monoclonal antibody (MAb), HA-7, that potently neutralized all tested strains of H5N1 covering clades 0, 1, 2.2, 2.3.4, and 2.3.2.1 and completely protected mice against lethal challenges of H5N1 viruses from clades 1 and 2.3.4. HA-7 specifically targeted the globular head of the H5N1 virus hemagglutinin (HA). Using electron microscopy technology with three-dimensional reconstruction (3D-EM), we discovered that HA-7 bound to a novel and highly conserved conformational epitope that was centered on residues 81 to 83 and 117 to 122 of HA1 (H5 numbering). We further demonstrated that HA-7 inhibited viral entry during postattachment events but not at the receptor-binding step, which is fully consistent with the 3D-EM result. Taken together, we propose that HA-7 could be humanized as an effective passive immunotherapeutic agent for antiviral stockpiling for future influenza pandemics caused by emerging unpredictable H5N1 strains. Our study also provides a sound foundation for the rational design of vaccines capable of inducing broad-spectrum immunity against H5N1.",,"['Du, Lanying', 'Jin, Lei', 'Zhao, Guangyu', 'Sun, Shihui', 'Li, Junfeng', 'Yu, Hong', 'Li, Ye', 'Zheng, Bo-Jian', 'Liddington, Robert C.', 'Zhou, Yusen', 'Jiang, Shibo']",,,,
,PMC,Identification of a Noncanonically Transcribed Subgenomic mRNA of Infectious Bronchitis Virus and Other Gammacoronaviruses,http://dx.doi.org/10.1128/JVI.02967-12,PMC3571483,,,"Coronavirus subgenomic mRNA (sgmRNA) synthesis occurs via a process of discontinuous transcription involving transcription regulatory sequences (TRSs) located in the 5′ leader sequence (TRS-L) and upstream of each structural and group-specific gene (TRS-B). Several gammacoronaviruses including infectious bronchitis virus (IBV) contain a putative open reading frame (ORF), localized between the M gene and gene 5, which is controversial due to the perceived absence of a TRS. We have studied the transcription of a novel sgmRNA associated with this potential ORF and found it to be transcribed via a previously unidentified noncanonical TRS-B. Using an IBV reverse genetics system, we demonstrated that the template-switching event during intergenic region (IR) sgmRNA synthesis occurs at the 5′ end of the noncanonical TRS-B and recombines between nucleotides 5 and 6 of the 8-nucleotide consensus TRS-L. Introduction of a complete TRS-B showed that higher transcription levels are achieved by increasing the number of nucleotide matches between TRS-L and TRS-B. Translation of a protein from the sgmRNA was demonstrated using enhanced green fluorescent protein, suggesting the translation of a fifth, novel, group-specific protein for IBV. This study has resolved an issue concerning the number of ORFs expressed by members of the Gammacoronavirus genus and proposes the existence of a fifth IBV accessory protein. We confirmed previous reports that coronaviruses can produce sgmRNAs from noncanonical TRS-Bs, which may expand their repertoire of proteins. We also demonstrated that noncanonical TRS-Bs may provide a mechanism by which coronaviruses can control protein expression levels by reducing sgmRNA synthesis.",,"['Bentley, Kirsten', 'Keep, Sarah May', 'Armesto, Maria', 'Britton, Paul']",,,,
,PMC,"Sequencing, Annotation, and Characterization of the Influenza Ferret Infectome",http://dx.doi.org/10.1128/JVI.02476-12,PMC3571481,,,"Ferrets have become an indispensable tool in the understanding of influenza virus virulence and pathogenesis. Furthermore, ferrets are the preferred preclinical model for influenza vaccine and therapeutic testing. Here we characterized the influenza infectome during the different stages of the infectious process in ferrets with and without prior specific immunity to influenza. RNA from lung tissue and lymph nodes from infected and naïve animals was subjected to next-generation sequencing, followed by de novo data assembly and annotation of the resulting sequences; this process generated a library comprising 13,202 ferret mRNAs. Gene expression profiles during pandemic H1N1 (pdmH1N1) influenza virus infection were analyzed by digital gene expression and solid support microarrays. As expected during primary infection, innate immune responses were triggered in the lung tissue; meanwhile, in the lymphoid tissue, genes encoding antigen presentation and maturation of effector cells of adaptive immunity increased dramatically. After 5 days postinfection, the innate immune gene expression was replaced by the adaptive immune response, which correlates with viral clearance. Reinfection with homologous pandemic influenza virus resulted in a diminished innate immune response, early adaptive immune gene regulation, and a reduction in clinical severity. The fully annotated ferret infectome will be a critical aid to the understanding of the molecular events that regulate disease severity and host-influenza virus interactions among seasonal, pandemic, and highly pathogenic avian influenzas.",,"['León, Alberto J.', 'Banner, David', 'Xu, Luoling', 'Ran, Longsi', 'Peng, Zhiyu', 'Yi, Kang', 'Chen, Chao', 'Xu, Fengping', 'Huang, Jinrong', 'Zhao, Zhen', 'Lin, Zhen', 'Huang, Stephen H. S.', 'Fang, Yuan', 'Kelvin, Alyson A.', 'Ross, Ted M.', 'Farooqui, Amber', 'Kelvin, David J.']",,,,
,PMC,"Neurotropic Arboviruses Induce Interferon Regulatory Factor 3-Mediated Neuronal Responses That Are Cytoprotective, Interferon Independent, and Inhibited by Western Equine Encephalitis Virus Capsid",http://dx.doi.org/10.1128/JVI.02858-12,PMC3554193,,,"Cell-intrinsic innate immune responses mediated by the transcription factor interferon regulatory factor 3 (IRF-3) are often vital for early pathogen control, and effective responses in neurons may be crucial to prevent the irreversible loss of these critical central nervous system cells after infection with neurotropic pathogens. To investigate this hypothesis, we used targeted molecular and genetic approaches with cultured neurons to study cell-intrinsic host defense pathways primarily using the neurotropic alphavirus western equine encephalitis virus (WEEV). We found that WEEV activated IRF-3-mediated neuronal innate immune pathways in a replication-dependent manner, and abrogation of IRF-3 function enhanced virus-mediated injury by WEEV and the unrelated flavivirus St. Louis encephalitis virus. Furthermore, IRF-3-dependent neuronal protection from virus-mediated cytopathology occurred independently of autocrine or paracrine type I interferon activity. Despite being partially controlled by IRF-3-dependent signals, WEEV also disrupted antiviral responses by inhibiting pattern recognition receptor pathways. This antagonist activity was mapped to the WEEV capsid gene, which disrupted signal transduction downstream of IRF-3 activation and was independent of capsid-mediated inhibition of host macromolecular synthesis. Overall, these results indicate that innate immune pathways have important cytoprotective activity in neurons and contribute to limiting injury associated with infection by neurotropic arboviruses.",,"['Peltier, Daniel C.', 'Lazear, Helen M.', 'Farmer, Jocelyn R.', 'Diamond, Michael S.', 'Miller, David J.']",,,,
,PMC,Cyclophilin Inhibitors Block Arterivirus Replication by Interfering with Viral RNA Synthesis,http://dx.doi.org/10.1128/JVI.02078-12,PMC3554155,,,"Virus replication strongly depends on cellular factors, in particular, on host proteins. Here we report that the replication of the arteriviruses equine arteritis virus (EAV) and porcine reproductive and respiratory syndrome virus (PRRSV) is strongly affected by low-micromolar concentrations of cyclosporine A (CsA), an inhibitor of members of the cyclophilin (Cyp) family. In infected cells, the expression of a green fluorescent protein (GFP) reporter gene inserted into the PRRSV genome was inhibited with a half-maximal inhibitory concentration (IC(50)) of 5.2 μM, whereas the GFP expression of an EAV-GFP reporter virus was inhibited with an IC(50) of 0.95 μM. Debio-064, a CsA analog that lacks its undesirable immunosuppressive properties, inhibited EAV replication with an IC(50) that was 3-fold lower than that of CsA, whereas PRRSV-GFP replication was inhibited with an IC(50) similar to that of CsA. The addition of 4 μM CsA after infection prevented viral RNA and protein synthesis in EAV-infected cells, and CsA treatment resulted in a 2.5- to 4-log-unit reduction of PRRSV or EAV infectious progeny. A complete block of EAV RNA synthesis was also observed in an in vitro assay using isolated viral replication structures. The small interfering RNA-mediated knockdown of Cyp family members revealed that EAV replication strongly depends on the expression of CypA but not CypB. Furthermore, upon fractionation of intracellular membranes in density gradients, CypA was found to cosediment with membranous EAV replication structures, which could be prevented by CsA treatment. This suggests that CypA is an essential component of the viral RNA-synthesizing machinery.",,"['de Wilde, Adriaan H.', 'Li, Yanhua', 'van der Meer, Yvonne', 'Vuagniaux, Grégoire', 'Lysek, Robert', 'Fang, Ying', 'Snijder, Eric J.', 'van Hemert, Martijn J.']",,,,
,PMC,Reply to “Codon Usage Frequency of RNA Virus Genomes from High-Temperature Acidic-Environment Metagenomes”,http://dx.doi.org/10.1128/JVI.02883-12,PMC3554147,,,,,"['Young, Mark', 'Bolduc, Benjamin', 'Shaughnessy, Daniel P.', 'Roberto, Francisco F.', 'Wolf, Yuri I.', 'Koonin, Eugene V.']",,,,
,PMC,Expression and Purification of the scFv from Hybridoma Cells Secreting a Monoclonal Antibody Against S Protein of PEDV,http://dx.doi.org/10.1089/mab.2012.0089,PMC4014299,,,"The variable regions of the heavy chain (VH) and light chain (VL) were amplified by RT-PCR from the hybridoma 6E6, which secretes the monoclonal antibody against PEDV S protein. The VL and VH amplicons were combined using SOE-PCR by a 12 amino acid flexible linker (SSGGGGSGGGGS), which produced the scFv gene (named scFv/6E6). After sequence analysis, the scFv/6E6 gene was cloned into the prokaryotic expression vector pGEX-6p-1 with a GST-tag. The recombinant scFv/6E6 protein was successfully expressed in recombinant Escherichia coli by IPTG induction. Moreover, the recombinant scFv/6E6 protein was purified from the inclusion body form by the gel-cutting measure followed by electroelution and dialysis. The recombinant scFv/6E6 protein reported here will provide some basis for further antiviral drug research based on the scFv molecule.",,"['Zhu, Qinghe', 'Guo, Donghua', 'Feng, Li', 'Sun, Dongbo']",,,,
,PMC,Mycobacterium tuberculosis Whole Cell Lysate Enhances Proliferation of CD8 Positive Lymphocytes and Nitric Oxide Secretion in the Lungs of Live Porcine Respiratory and Reproductive Syndrome Virus Vaccinated Pigs,http://dx.doi.org/10.1089/vim.2012.0065,PMC4180527,,,"Porcine respiratory and reproductive syndrome (PRRS) is an economically important disease of pigs worldwide. Currently used PRRSV vaccines provide incomplete protection. Recently, we identified Mycobacterium tuberculosis whole cell lysate (Mtb WCL) as a potent mucosal adjuvant to modified live PRRSV vaccine (PRRS-MLV). In this study, pigs were unvaccinated or vaccinated with PRRS-MLV plus Mtb WCL, intranasally, and challenged with either homologous (strain VR2332) or virulent heterologous (strain MN184) PRRSV; subsequently, euthanized at three time points post-challenge to evaluate lung immune responses. Microscopic examination of lung sections revealed reduced disruption of the lung architecture and less of interstitial pneumonia in vaccinated, compared to unvaccinated MN184 challenged pigs. The restimulated lung and peripheral blood mononuclear cells revealed increased proliferation of CD8(+) lymphocytes, and in the lung homogenate increased secretion of nitric oxide was detected in vaccinated MN184 challenged pigs. In summary, the adjuvant effects of Mtb WCL to PRRS-MLV resulted in favorable anti-PRRSV immune microenvironment in the lungs to help better viral clearance.",,"['Manickam, Cordelia', 'Dwivedi, Varun', 'Miller, Jayla', 'Papenfuss, Tracey', 'Renukaradhya, Gourapura J.']",,,,
,PMC,Autophagy and Viruses: Adversaries or Allies?,http://dx.doi.org/10.1159/000346388,PMC3790331,,,"The autophagy pathway is an essential component of host defense against viral infection, orchestrating pathogen degradation (xenophagy), innate immune signaling, and certain aspects of adaptive immunity. Single autophagy proteins or cassettes of the core autophagy machinery can also function as antiviral factors independently of the canonical autophagy pathway. Moreover, to survive and propagate within the host, viruses have evolved a variety of strategies to evade autophagic attack and manipulate the autophagy machinery for their own benefit. This review summarizes recent advances in understanding the antiviral and proviral roles of autophagy and previously unappreciated autophagy-independent functions of autophagy-related genes.",,"['Dong, Xiaonan', 'Levine, Beth']",,,,
,PMC,Human Vγ9Vδ2-T cells efficiently kill influenza virus-infected lung alveolar epithelial cells,http://dx.doi.org/10.1038/cmi.2012.70,PMC4003054,,,"γδ-T cells play an indispensable role in host defense against different viruses, including influenza A virus. However, whether these cells have cytotoxic activity against influenza virus-infected lung alveolar epithelial cells and subsequently contribute to virus clearance remains unknown. Using influenza virus-infected A549 cells, human lung alveolar epithelial cells, we investigated the cytotoxic activity of aminobisphosphonate pamidronate (PAM)-expanded human Vγ9Vδ2-T cells and their underlying mechanisms. We found that PAM could selectively activate and expand human Vγ9Vδ2-T cells. PAM-expanded human Vγ9Vδ2-T cells efficiently killed influenza virus-infected lung alveolar epithelial cells and inhibited virus replication. The cytotoxic activity of PAM-expanded Vγ9Vδ2-T cells was dependent on cell-to-cell contact and required NKG2D activation. Perforin–granzyme B, tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas–Fas ligand (FasL) pathways were involved in their cytotoxicity. Our study suggests that targeting γδ-T cells by PAM can potentially offer an alternative option for the treatment of influenza virus.",,"['Li, Hong', 'Xiang, Zheng', 'Feng, Ting', 'Li, Jinrong', 'Liu, Yinping', 'Fan, Yingying', 'Lu, Qiao', 'Yin, Zhongwei', 'Yu, Meixing', 'Shen, Chongyang', 'Tu, Wenwei']",,,,
,PMC,The 10(th) Anniversary of Carbohydrate Microarrays (2002–2012),,PMC4002048,,,,,"['Wang, Denong', 'Collins, Nathan']",,,,
,PMC,Systemic Causes of Cholestasis,http://dx.doi.org/10.1016/j.cld.2012.11.001,PMC4378837,,,,,"['deLemos, Andrew S.', 'Friedman, Lawrence S.']",,,,
,PMC,Streamlined Protocol for mRNA Display,http://dx.doi.org/10.1021/co300135r,PMC3666848,,,"mRNA display is a powerful method for in vitro directed evolution of polypeptides, but its time-consuming, technically demanding nature has hindered its widespread use. We present a streamlined protocol in which lengthy mRNA purification steps are replaced with faster precipitation and ultrafiltration alternatives; additionally, other purification steps are entirely eliminated by using a reconstituted translation system and by performing reverse transcription after selection, which also protects input polypeptides from thermal denaturation. We tested this procedure by performing affinity selection against Her2 using binary libraries containing a non-specific designed ankyrin repeat protein (DARPin) doped with a Her2-binding DARPin (dopant fraction ranging from 1:10 to 1:10,000). The Her2-binding DARPin was recovered in all cases, with an enrichment factor of up to two orders of magnitude per selection round. The time required for one round is reduced from 4–7 days to 2 days with our protocol, thus simplifying and accelerating mRNA display experiments.",,"['Barendt, Pamela A.', 'Ng, Daphne T.W.', 'McQuade, Casey N.', 'Sarkar, Casim A.']",,,,
,PMC,Compromised respiratory function in lethal influenza infection is characterized by the depletion of type I alveolar epithelial cells beyond threshold levels,http://dx.doi.org/10.1152/ajplung.00343.2012,PMC3627938,,,"During influenza virus infection, it is unclear how much alveolar cell loss can be tolerated before the host succumbs to the disease. We sought to define relevant correlates of disease severity in the mouse influenza model, hypothesizing that a susceptibility threshold exists for alveolar epithelial cell loss. We compared lung pathology, virus spread, alveolar epithelial cell depletion, arterial blood oxygenation, physiological responses measured by unrestrained plethysmography, and oxygen consumption and carbon dioxide production by gas analysis in mice at intervals after infection with virus strains and doses that cause mild (x31) or severe (PR/8) influenza. Both mild and severe infections showed similar degrees of lung damage and virus dissemination until day 6 after inoculation but diverged in survival outcomes from day 9. Day 6 PR/8-infected mice had normal respiratory and gas exchange functions with 10% type I cell loss. However, day 10 PR/8-infected mice had 40% type I cell loss with a concomitant drastic decreases in tidal and minute volumes, V̇o(2), V̇co(2), and arterial blood oxygenation, compared with a maximum 3% type I cell loss for x31 on day 10 when they recovered body weight and respiratory functions. Alterations in breaths per minute, expiratory time, and metabolic rate were observed in both infections. A threshold for maintenance of proper respiratory function appears to be crossed once 10% of alveolar type I cells are lost. These data indicate that lethality in influenza virus infection is a matter of degree rather than quality.",,"['Sanders, Catherine J.', 'Vogel, Peter', 'McClaren, Jennifer L.', 'Bajracharya, Resha', 'Doherty, Peter C.', 'Thomas, Paul G.']",,,,
,PMC,Non-autophagic roles of autophagy-related proteins,http://dx.doi.org/10.1038/embor.2012.220,PMC3566844,,,"Autophagy and autophagy-related processes are fundamentally important in human health and disease. These processes are viewed primarily as cellular degradative pathways that recycle macromolecules and dysfunctional or redundant organelles into amino acids, sugars and lipids, especially during starvation. However, the ubiquitin-like autophagy proteins and other components of the autophagic machinery additionally participate in cellular reprogramming. We highlight these non-autophagic roles of autophagy proteins with the aim of drawing attention to this growing, but unexplored, research topic. We focus on the non-autophagic functions of autophagy proteins in cell survival and apoptosis, modulation of cellular traffic, protein secretion, cell signalling, transcription, translation and membrane reorganization.",,"['Subramani, Suresh', 'Malhotra, Vivek']",,,,
,PMC,Lessons learned and concepts formed from study of the pathogenesis of the two negative-strand viruses lymphocytic choriomeningitis and influenza,http://dx.doi.org/10.1073/pnas.1222025110,PMC3600446,,,"Viruses have unique lifestyles. To describe the pathogenesis and significance of viral infection in terms of host responses, resultant injury, and therapy, we focused on two RNA viruses: lymphocytic choriomeningitis (LCMV) and influenza (Flu). Many of the currently established concepts and consequences about viruses and immunologic tolerance, virus-induced immunosuppression, virus-induced autoimmunity, immune complex disease, and virus–lymphocyte and virus–dendritic cell interactions evolved through studies of LCMV in its natural murine host. Similarly, the mechanisms, aftermath, and treatment of persistent RNA viruses emerged, in large part, from research on LCMV. Analysis of acute influenza virus infections uncovered the prominent direct role that cytokine storm plays in the pathogenesis, morbidity, and mortality from this disease. Cytokine storm of influenza virus infection is initiated via a pulmonary endothelial cell amplification loop involving IFN-producing cells and virus-infected pulmonary epithelial cells. Importantly, the cytokine storm is chemically treatable with specific agonist therapy directed to the sphingosphine 1 phosphate receptor 1, which is located on pulmonary endothelial cells, pointing to the endothelial cells as the gatekeepers of this hyperaggressive host immune response.",,"Oldstone, Michael B. A.",,,,
,PMC,Long non-coding RNAs (lncRNAs) and viral infections,http://dx.doi.org/10.1016/j.biomed.2013.01.001,PMC3641704,,,"In this review, we focus on the roles of lncRNAs, including cellular and viral lncRNAs, in virus replication in infected cells. We survey the interactions and functions of several cellular lncRNAs such as XIST, HOTAIR, NEAT1, BIC and several virus encoded lncRNAs.",,"['Zhang, Quan', 'Jeang, Kuan-Teh']",,,,
,PMC,Visualizing the autophagy pathway in avian cells and its application to studying infectious bronchitis virus,http://dx.doi.org/10.4161/auto.23465,PMC3627666,,,"Autophagy is a highly conserved cellular response to starvation that leads to the degradation of organelles and long-lived proteins in lysosomes and is important for cellular homeostasis, tissue development and as a defense against aggregated proteins, damaged organelles and infectious agents. Although autophagy has been studied in many animal species, reagents to study autophagy in avian systems are lacking. Microtubule-associated protein 1 light chain 3 (MAP1LC3/LC3) is an important marker for autophagy and is used to follow autophagosome formation. Here we report the cloning of avian LC3 paralogs A, B and C from the domestic chicken, Gallus gallus domesticus, and the production of replication-deficient, recombinant adenovirus vectors expressing these avian LC3s tagged with EGFP and FLAG-mCherry. An additional recombinant adenovirus expressing EGFP-tagged LC3B containing a G120A mutation was also generated. These vectors can be used as tools to visualize autophagosome formation and fusion with endosomes/lysosomes in avian cells and provide a valuable resource for studying autophagy in avian cells. We have used them to study autophagy during replication of infectious bronchitis virus (IBV). IBV induced autophagic signaling in mammalian Vero cells but not primary avian chick kidney cells or the avian DF1 cell line. Furthermore, induction or inhibition of autophagy did not affect IBV replication, suggesting that classical autophagy may not be important for virus replication. However, expression of IBV nonstructural protein 6 alone did induce autophagic signaling in avian cells, as seen previously in mammalian cells. This may suggest that IBV can inhibit or control autophagy in avian cells, although IBV did not appear to inhibit autophagy induced by starvation or rapamycin treatment.",,"['Maier, Helena J.', 'Cottam, Eleanor M.', 'Stevenson-Leggett, Phoebe', 'Wilkinson, Jessica A.', 'Harte, Christopher J.', 'Wileman, Tom', 'Britton, Paul']",,,,
,PMC,"A Clinical Perspective of Necrotizing Enterocolitis: Past, Present, and Future",http://dx.doi.org/10.1016/j.clp.2012.12.012,PMC3575605,,,,,"['Sharma, Renu', 'Hudak, Mark Lawrence']",,,,
,PMC,Sequence and immunogenicity of a clinically approved novel measles virus vaccine vector,http://dx.doi.org/10.4161/hv.23242,PMC3891718,,,"The measles virus vaccine (MVbv) is a clinically certified and well-tolerated vaccine strain that has been given both parenterally and mucosally. It has been extensively used in children and has proven to be safe and effective in eliciting protective immunity. This specific strain was therefore chosen to generate a measles viral vector. The genome of the commercial MVbv vaccine strain was isolated, sequenced and a plasmid, p(+)MVb, enabling transcription of the viral antigenome and rescue of MVb, was constructed. Phylogenic and phenotypic analysis revealed that MVbv and the rescued MVb constitute another evolutionary branch within the hitherto classified measles vaccines. Plasmid p(+)MVb was modified by insertion of artificial MV-type transcription units (ATUs) for the generation of recombinant viruses (rMVb) expressing additional proteins. Replication characteristics and immunogenicity of rMVb vectors were similar to the parental MVbv and to other vaccine strains. The expression of the additional proteins was stable over 10 serial virus transfers, which corresponds to an amplification greater than 10(20). The excellent safety record and its efficient application as aerosol may add to the usefulness of the derived vectors.",,"['Zuniga, Amando', 'Liniger, Mathias', 'Morin, Teldja Neige Azzouz', 'Marty, René R.', 'Wiegand, Marian', 'Ilter, Orhan', 'Weibel, Sara', 'Billeter, Martin A.', 'Knuchel, Marlyse C.', 'Naim, Hussein Y.']",,,,
,PMC,Relevance of a pre-existing measles immunity prior immunization with a recombinant measles virus vector,http://dx.doi.org/10.4161/hv.23241,PMC3891717,,,"Measles virus (MV) vectors are promising candidates for designing new recombinant vaccines since the parental live vaccines have a well-known safety and efficacy record. Like all viral vectors, the MV vector efficacy in inducing a protecting immune answer could be affected by the pre-existing immunity among the human population. In order to determine the optimal immunization route and regimen, we mimicked a MV pre-immunity by passively administrating MV neutralizing antibodies (MV-nAb) prior intramuscular (i.m.) and/or intranasal (i.n.) immunization with recombinant MV expressing the SIV-gag antigen (rMV-SIVgag). Our results revealed that 500 mIU of MV-nAb allowed the induction of a humoral and cellular immune response against the vector and the transgene, while higher titers of the MV-nAb were significantly inhibitory. In a prime-boost regimen, in the presence of MV-nAb, the intranasal-intramuscular (i.n.-i.m.) or intramuscular-intramuscular (i.m.-i.m.) routes induced higher humoral immune responses against the vector and the transgene (SIV-gag). In naive animals, cellular immune response was significantly higher by i.m. immunization; however, MV pre-immunity did not seem to affect the cellular immune response after an i.n. immunization. In summary, we show that a pre-existing immunity of up to 500 mIU anti-MV neutralizing antibodies had little effect on the replication of rMV and did not inhibit the induction of significant humoral and cellular immune responses in immune-competent mice.",,"['Knuchel, Marlyse C.', 'Marty, René R.', 'Morin, Teldja Neige Azzouz', 'Ilter, Orhan', 'Zuniga, Armando', 'Naim, Hussein Y.']",,,,
,PMC,"IL-27 enhances the survival of tumor antigen-specific CD8(+) T cells and programs them into IL-10-producing, memory precursor-like effector cells",http://dx.doi.org/10.1002/eji.201242930,PMC3625660,,,"IL-27 is a member of the IL-12 family of cytokines that is comprised of an IL-12 p40-related protein subunit, EBV-induced gene 3 (EBI3), and a p35-related subunit, p28. IL-27 functions through IL-27R and has been shown to have potent anti-tumor activity via activation of a variety of cellular components, including anti-tumor CD8(+) T-cell responses. However, the exact mechanisms of how IL-27 enhances anti-tumor CD8(+) T-cell responses remain unclear. Here we show that IL-27 significantly enhances the survival of activated tumor antigen specific CD8(+) T cells in vitro and in vivo, and programs tumor antigen-specific CD8(+) T cells into memory precursor (MPC)-like effector cells, characterized by upregulation of Bcl-6, SOCS3, Sca-1, and IL-10. While STAT3 activation and the CTL survival-enhancing effects can be independent of CTL IL-10 production, we show here that IL-27-induced CTL IL-10 production contributes to MPC phenotype induction, CTL memory, and tumor rejection. Thus, IL-27 enhances anti-tumor CTL responses via programming tumor antigen-specific CD8(+) T cells into a unique memory precursor-type of effector cells characterized by a greater survival advantage. Our results have important implications for designing immunotherapy against human cancer.",,"['Liu, Zhenzhen', 'Liu, Jin-Qing', 'Talebian, Fatemeh', 'Wu, Lai-Chu', 'Li, Shulin', 'Bai, Xue-Feng']",,,,
,PMC,Mucosal Lactobacillus vectored vaccines,http://dx.doi.org/10.4161/hv.23302,PMC3903899,,,"Traditional non-gastrointestinal vaccines can prevent effectively the invasion of pathogens; however, these vaccines are less effective against mucosal infections because there is not a sufficient immune response at the mucosa. Most pathogens invade via a mucosal pathway (oral, intranasal, or vaginal).(1) It is widely accepted that Lactobacillus species play a critical role as commensals in the gastrointestinal (GI) tract.(2) Their ability to survive in the digestive tract, their close association with the intestinal epithelium, their immunomodulatory properties and their safety even when consumed in large amounts make lactobacilli attractive candidates for live vehicles for the delivery of immunogens to the intestinal mucosa.(3) The oral or intranasal administration of Lactobacillus-based vaccines is a promising method to control mucosal infection because these vaccines could induce strong humoral and cellular immune responses both in the blood and at mucosal sites.",,"['Yu, Qinghua', 'Zhu, Liqi', 'Kang, Haihong', 'Yang, Qian']",,,,
,PMC,Emerging roles for protein S-palmitoylation in immunity from chemical proteomics,http://dx.doi.org/10.1016/j.cbpa.2012.11.008,PMC4000526,,,The activation of innate and adaptive immune signaling pathways and effector functions often occur at cellular membranes and are regulated by complex mechanisms. Here we review the growing number of proteins known to be regulated by S-palmitoylation in immune cells emerging from recent advances in chemical proteomics. These chemical proteomic studies have highlighted the roles of this dynamic lipid modification in regulating the specificity and strength of immune responses in different lymphocyte populations.,,"['Yount, Jacob S.', 'Zhang, Mingzi M.', 'Hang, Howard C.']",,,,
,PMC,"Association of Serum Albumin Concentration With Mortality, Morbidity, CD4 T-cell Reconstitution Among Tanzanians Initiating Antiretroviral Therapy",http://dx.doi.org/10.1093/infdis/jit027,PMC3610420,,,"Background. Prospective studies of serum albumin concentration measurement as a low-cost predictor of human immunodeficiency virus (HIV) disease progression are needed for individuals initiating antiretroviral therapy (ART) in resource-limited settings. Methods. Serum albumin concentration was measured at ART initiation for 2145 adults in Tanzania who were enrolled in a trial examining the effect of multivitamins on HIV disease progression. Participants were prospectively followed for mortality, morbidity, and anthropometric outcomes at monthly visits (median follow-up duration, 21.2 months). Proportional hazard models were used to analyze mortality, morbidity, and nutritional outcomes, while generalized estimating equations were used to analyze CD4(+) T-cell counts. Results. Individuals with hypoalbuminemia (defined as a serum albumin concentration of <35 g/L) at ART initiation had a hazard of death that was 4.52 times (95% confidence interval, 3.37–6.07; P < .001) that of individuals with serum albumin concentrations of ≥35 g/L, after multivariate adjustment. Hypoalbuminemia was also independently associated with the incidence of pulmonary tuberculosis (P < .001), severe anemia (P < .001), wasting (P = .002), and >10% weight loss (P = .012). Secondary analyses suggested that serum albumin concentrations of <38 g/L were associated with increased mortality and incident pulmonary tuberculosis. There was no association between serum albumin concentration and changes in CD4(+) T-cell counts (P = .121). Conclusions. Serum albumin concentrations can identify adults initiating ART who are at high risk for mortality and selected morbidities. Future research is needed to identify and manage conditions that reduce the serum albumin concentration.",,"['Sudfeld, Christopher R.', 'Isanaka, Sheila', 'Aboud, Said', 'Mugusi, Ferdinand M.', 'Wang, Molin', 'Chalamilla, Guerino E.', 'Fawzi, Wafaie W.']",,,,
,PMC,Barriers of hepatitis C virus interspecies transmission,http://dx.doi.org/10.1016/j.virol.2012.09.044,PMC3523278,,,"Hepatitis C virus (HCV) is a major causative agent of severe liver disease including fibrosis, cirrhosis and liver cancer. Therapy has improved over the years, but continues to be associated with adverse side effects and variable success rates. Furthermore, a vaccine protecting against HCV infection remains elusive. Development of more effective intervention measures has been delayed by the lack of a suitable animal model. Naturally, HCV infects only humans and chimpanzees. The determinants of this limited host range are poorly understood in part due to difficulties of studying HCV in cell culture. Some progress has been made elucidating the barriers for the HCV lifecycle in non-permissive species which will help in the future to construct animal models for HCV infection, immunity and pathogenesis.",,"['Sandmann, Lisa', 'Ploss, Alexander']",,,,
,PMC,The chemokine receptor CXCR2 and coronavirus-induced neurologic disease,http://dx.doi.org/10.1016/j.virol.2012.08.049,PMC3522860,,,"Inoculation of the neurotropic JHM strain of mouse hepatitis virus (MHV) into the central nervous system (CNS) of susceptible strains of mice results in an acute encephalomyelitis in which virus preferentially replicates within glial cells while excluding neurons. Control of viral replication during acute disease is mediated by infiltrating virus-specific T cells via cytokine secretion and cytolytic activity, however sterile immunity is not achieved and virus persists resulting in chronic neuroinflammation associated with demyelination. CXCR2 is a chemokine receptor that upon binding to specific ligands promotes host defense through recruitment of myeloid cells to the CNS as well as protecting oligodendroglia from cytokine-mediated death in response to MHV infection. These findings highlight growing evidence of the diverse and important role of CXCR2 in regulating neuroinflammatory diseases.",,"['Weinger, Jason G.', 'Marro, Brett S.', 'Hosking, Martin P.', 'Lane, Thomas E.']",,,,
,PMC,"Discovery, synthesis, and structure-based optimization of a series of N-(tert-butyl)-2-(N-arylamido)-2-(pyridin-3-yl) acetamides (ML188) as potent non-covalent small molecule inhibitors of the severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL protease",http://dx.doi.org/10.1021/jm301580n,PMC3569073,,,"A high-throughput screen of the NIH molecular libraries sample collection and subsequent optimization of a lead dipeptide-like series of severe acute respiratory syndrome (SARS) main protease (3CLpro) inhibitors led to the identification of probe compound ML188 (16-(R), (R)-N-(4-(tert-butyl)phenyl)-N-(2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl)furan-2-carboxamide, Pubchem CID: 46897844). Unlike the majority of reported coronavirus 3CLpro inhibitors that act via covalent modification of the enzyme, 16-(R) is a non-covalent SARS-CoV 3CLpro inhibitor with moderate MW and good enzyme and antiviral inhibitory activity. A multi-component Ugi reaction was utilized to rapidly explore structure activity relationships within S(1′), S(1), and S(2) enzyme binding pockets. The X-ray structure of SARS-CoV 3CLpro bound with 16-(R) was instrumental in guiding subsequent rounds of chemistry optimization. 16-(R) provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a non-covalent mechanism of action.",,"['Jacobs, Jon', 'Tokars, Valerie', 'Zhou, Ya', 'Turlington, Mark', 'Saldanha, S. Adrian', 'Chase, Peter', 'Eggler, Aimee', 'Dawson, Eric S.', 'Baez-Santos, Yahira M.', 'Tomar, Sakshi', 'Mielech, Anna M.', 'Baker, Susan C.', 'Lindsley, Craig W.', 'Hodder, Peter', 'Mesecar, Andrew', 'Stauffer, Shaun R.']",,,,
,PMC,The changing face of pathogen discovery and surveillance,http://dx.doi.org/10.1038/nrmicro2949,PMC4098826,,,"The pace of pathogen discovery is increasing dramatically. This reflects not only factors that enable the appearance and globalization of new microbial infections but also improvements in methods for ascertainment. New molecular diagnostic platforms; investments in pathogen surveillance in wildlife, domestic animals and humans; and the advent of social media tools that mine the world wide web for clues to outbreaks of infectious disease are proving invaluable in early recognition of threats to public health. Additionally, models of microbial pathogenesis are becoming more complex, providing insights into the mechanisms by which microorganisms can contribute to chronic illnesses like cancer, peptic ulcer disease and mental illness. Here we review the contributions of each of these elements to infectious disease emergence and strategies for addressing the challenges of pathogen surveillance and discovery.",,"Lipkin, W. Ian",,,,
,PMC,Diversion of Stress Granules and P-Bodies During Viral Infection,http://dx.doi.org/10.1016/j.virol.2012.11.017,PMC3611887,,,"RNA granules are structures within cells that impart key regulatory measures on gene expression. Two general types of RNA granules are conserved from yeast to mammals: stress granules (SGs), which contain many translation initiation factors, and processing bodies (P-bodies, PBs), which are enriched for proteins involved in RNA turnover. Because of the inverse relationship between appearance of RNA granules and persistence of translation, many viruses must subvert RNA granule function for replicative purposes. Here we discuss the viruses and mechanisms that manipulate stress granules and P-bodies to promote synthesis of viral proteins. Several themes have emerged for manipulation of RNA granules by viruses: 1) disruption of RNA granules at the mid-phase of infection, 2) prevention of RNA granule assembly throughout infection, and 3) co-opting of RNA granule proteins for new or parallel roles in viral reproduction. Viruses must employ one or multiple of these routes for a robust and productive infection to occur. The possible role for RNA granules in promoting innate immune responses poses an additional reason why viruses must counteract the effects of RNA granules for efficient replication.",,"['Reineke, Lucas C.', 'Lloyd, Richard E.']",,,,
,PMC,Relationship of GW/P-Bodies with Stress Granules,http://dx.doi.org/10.1007/978-1-4614-5107-5_12,PMC4317337,,,"Whereas P-bodies are intimately linked to the cytoplasmic RNA decay machinery, stress granules harbor stalled translation initiation complexes that accumulate upon stress-induced translation arrest. In this Chapter, we reflect on the relationship between P-bodies and stress granules. In mammalian cells, the two structures can be clearly distinguished from each other using specific protein or RNA markers, but they also share many proteins and mRNAs. While the formation of P-bodies and stress granules is coordinately triggered by stress, their assembly appears to be regulated independently by different pathways. Under certain types of stress, P-bodies frequently dock with stress granules, and overexpressing certain proteins that localize to both structures can cause P-body/stress granule fusion. Currently available data suggest that these self-assembling compartments are controlled by flux of mRNAs within the cytoplasm, and that their assembly mirrors the translation and degradation rates of their component mRNAs.",,"['Stoecklin, Georg', 'Kedersha, Nancy']",,,,
,PMC,Intracellular pathogen detection by RIG-I-like receptors,http://dx.doi.org/10.1016/B978-0-12-410524-9.00004-9,PMC3947775,,,"The RIG-I-like receptors (RLR) RIG-I, MDA5 and LGP2 trigger innate immune responses against viral infections that serve to limit virus replication and to stimulate adaptive immunity. RLRs are cytosolic sensors for virus-derived RNA and thus responsible for intracellular immune surveillance against infection. RLR signaling requires the adapter protein MAVS to induce type I interferon, interferon-stimulated genes and proinflammatory cytokines. This review focusses on the molecular and cell biological requirements for RLR signal transduction.",,"['Dixit, Evelyn', 'Kagan, Jonathan C.']",,,,
,PMC,Mechanisms of Reovirus Bloodstream Dissemination,http://dx.doi.org/10.1016/B978-0-12-407698-3.00001-6,PMC4603565,,,"Many viruses cause disease within an infected host after spread from an initial portal of entry to secondary sites of replication. Viruses can disseminate via the bloodstream or through nerves. Mammalian orthoreoviruses (reoviruses) are neurotropic viruses that use both bloodborne and neural pathways to spread systemically within their hosts to cause disease. Using a robust mouse model and a dynamic reverse genetics system, we have identified a viral receptor and a viral nonstructural protein that are essential for hematogenous reovirus dissemination. Junctional adhesion molecule-A (JAM-A) is a member of the immunoglobulin superfamily expressed in tight junctions and on hematopoietic cells that serves as a receptor for all reovirus serotypes. Expression of JAM-A is required for infection of endothelial cells and development of viremia in mice, suggesting that release of virus into the bloodstream from infected endothelial cells requires JAM-A. Nonstructural protein σ1s is implicated in cell cycle arrest and apoptosis in reovirus-infected cells but is completely dispensable for reovirus replication in cultured cells. Surprisingly, a recombinant σ1s-null reovirus strain fails to spread hematogenously in infected mice, suggesting that σ1s facilitates apoptosis of reovirus-infected intestinal epithelial cells. It is possible that apoptotic bodies formed as a consequence of σ1s expression lead to reovirus uptake by dendritic cells for subsequent delivery to the mesenteric lymph node and the blood. Thus, both host and viral factors are required for efficient hematogenous dissemination of reovirus. Understanding mechanisms of reovirus bloodborne spread may shed light on how microbial pathogens invade the bloodstream to disseminate and cause disease in infected hosts.",,"['Boehme, Karl W.', 'Lai, Caroline M.', 'Dermody, Terence S.']",,,,
,PMC,Aerosol Generation by Modern Flush Toilets,http://dx.doi.org/10.1080/02786826.2013.814911,PMC4666014,,,"A microbe-contaminated toilet will produce bioaerosols when flushed. We assessed toilet plume aerosol from high efficiency (HET), pressure-assisted high efficiency (PAT), and flushometer (FOM) toilets with similar bowl water and flush volumes. Total and droplet nuclei “bioaerosols” were assessed. Monodisperse 0.25–1.9-μm fluorescent microspheres served as microbe surrogates in separate trials in a mockup 5 m(3) water closet (WC). Bowl water seeding was approximately 10(12) particles/mL. Droplet nuclei were sampled onto 0.2-μm pore size mixed cellulose ester filters beginning 15 min after the flush using open-face cassettes mounted on the WC walls. Pre- and postflush bowl water concentrations were measured. Filter particle counts were analyzed via fluorescent microscopy. Bowl headspace droplet count size distributions were bimodal and similar for all toilet types and flush conditions, with 95% of droplets <2 μm diameter and >99% <5 μm. Up to 145,000 droplets were produced per flush, with the high-energy flushometer producing over three times as many as the lower energy PAT and over 12 times as many as the lowest energy HET despite similar flush volumes. The mean numbers of fluorescent droplet nuclei particles aerosolized and remaining airborne also increased with flush energy. Fluorescent droplet nuclei per flush decreased with increasing particle size. These findings suggest two concurrent aerosolization mechanisms—splashing for large droplets and bubble bursting for the fine droplets that form droplet nuclei.",,"['Johnson, David', 'Lynch, Robert', 'Marshall, Charles', 'Mead, Kenneth', 'Hirst, Deborah']",,,,
,PMC,A Decision Process for Determining Whether to Conduct Responder Health Research Following Disasters,http://dx.doi.org/10.5055/ajdm.2013.0108,PMC4593614,,,"BACKGROUND: Disasters often set the stage for scientific inquiry within the field of occupational safety and health. This is especially true when the long-term consequences of exposures associated with a particular disaster are unclear. However, a responder research study can be costly and difficult to design, and researchers must consider whether the proposed study will produce useful, reliable results and is a prudent public health investment. METHODS: Senior NIOSH scientists, experienced with disaster response and representing the disciplines of epidemiology, occupational medicine and psychiatry, and industrial hygiene, were convened at the request of the NIOSH Director to develop a decision process to help determine when to conduct responder health research following disasters. RESULTS: The decision process can be broken down into various components, including scientific rationale that should be formally recognized as critical to efficiently and effectively determine whether a research study is warranted. The scientific rationale includes certain controlling or “gatekeeper” factors that should be present to proceed with research. Providing the foundation for responder disaster research also requires strategizing before an event occurs, so that critical baseline and comparison data can be collected. CONCLUSIONS: The recommended framework should ensure that research that is most needed and justified will be identified and prioritized.",,"['Decker, John A.', 'Kiefer, Max', 'Reissman, Dori B.', 'Funk, Renée', 'Halpin, John', 'Bernard, Bruce', 'Ehrenberg, Richard L.', 'Schuler, Christine R.', 'Whelan, Elizabeth', 'Myers, Kyle', 'Howard, John']",,,,
,PMC,CXCL10-CXCR3 Enhances the Development of Neutrophil-mediated Fulminant Lung Injury of Viral and Nonviral Origin,http://dx.doi.org/10.1164/rccm.201203-0508OC,PMC3927876,,,"Rationale: Patients who developed acute respiratory distress syndrome (ARDS) after infection with severe respiratory viruses (e.g., severe acute respiratory syndrome–coronavirus, H5N1 avian influenza virus), exhibited unusually high levels of CXCL10, which belongs to the non-ELR (glutamic-leucine-arginine) CXC chemokine superfamily. CXCL10 may not be a bystander to the severe virus infection but may directly contribute to the pathogenesis of neutrophil-mediated, excessive pulmonary inflammation. Objectives: We investigated the contribution of CXCL10 and its receptor CXCR3 axis to the pathogenesis of ARDS with nonviral and viral origins. Methods: We induced nonviral ARDS by acid aspiration and viral ARDS by intratracheal influenza virus infection in wild-type mice and mice deficient in CXCL10, CXCR3, IFNAR1 (IFN-α/β receptor 1), or TIR domain-containing adaptor inducing IFN-β (TRIF). Measurements and Main Results: We found that the mice lacking CXCL10 or CXCR3 demonstrated improved severity and survival of nonviral and viral ARDS, whereas mice that lack IFNAR1 did not control the severity of ARDS in vivo. The increased levels of CXCL10 in lungs with ARDS originate to a large extent from infiltrated pulmonary neutrophils, which express a unique CXCR3 receptor via TRIF. CXCL10-CXCR3 acts in an autocrine fashion on the oxidative burst and chemotaxis in the inflamed neutrophils, leading to fulminant pulmonary inflammation. Conclusions: CXCL10-CXCR3 signaling appears to be a critical factor for the exacerbation of the pathology of ARDS. Thus, the CXCL10-CXCR3 axis could represent a prime therapeutic target in the treatment of the acute phase of ARDS of nonviral and viral origins.",,"['Ichikawa, Akihiko', 'Kuba, Keiji', 'Morita, Masayuki', 'Chida, Shinsuke', 'Tezuka, Hiroyuki', 'Hara, Hiromitsu', 'Sasaki, Takehiko', 'Ohteki, Toshiaki', 'Ranieri, V. Marco', 'dos Santos, Claudia C.', 'Kawaoka, Yoshihiro', 'Akira, Shizuo', 'Luster, Andrew D.', 'Lu, Bao', 'Penninger, Josef M.', 'Uhlig, Stefan', 'Slutsky, Arthur S.', 'Imai, Yumiko']",,,,
,PMC,10 years later...,,PMC3904997,,,,,"['Valiquette, Louis', 'Laupland, Kevin B']",,,,
,PMC,An investigation into the association between cpb2-encoding Clostridium perfringens type A and diarrhea in neonatal piglets,,PMC3525171,,,"To investigate the possible role of cpb2-positive type A Clostridium perfringens in neonatal diarrheal illness in pigs, the jejunum and colon of matched normal and diarrheic piglets from 10 farms with a history of neonatal diarrhea were examined grossly and by histopathology, and tested for C. perfringens, for C. perfringens beta2 (CPB2) toxin, as well as for Clostridium difficile toxins, Salmonella, enterotoxigenic Escherichia coli, rotavirus, transmissible gastroenteritis (TGE) virus, and coccidia. Clostridium perfringens isolates were tested using a multiplex real-time polymerase chain reaction (PCR) to determine the presence of cpa, consensus and atypical cpb2, and other virulence-associated genes. The numbers of C. perfringens in the intestinal contents were lower in diarrheic piglets (log(10) 5.4 CFU/g) compared with normal piglets (log(10) 6.5 CFU/g) (P < 0.05). The consensus cpb2 was present in 93% of isolates in each group, but atypical cpb2 was less common (56% healthy, 32% diarrheic piglets isolates, respectively, P < 0.05). The presence of CPB2 toxin in the intestinal contents of normal and diarrheic piglets did not differ significantly. Clostridium difficile toxins and rotavirus were each detected in 7 of the 21 (33%) diarrheic piglets. Rotavirus, C. difficile toxins, Salmonella, or enterotoxigenic E. coli were concurrently recovered in different combinations in 4 diarrheic piglets. The cause of diarrhea in 8 of the 21 (38%) piglets on 6 farms remained unknown. The etiological diagnosis of diarrhea could not be determined in any of the piglets on 2 of the farms. This study demonstrated that the number of cpb2-positive type A C. perfringens in the intestinal contents was not a useful approach for making a diagnosis of type A C. perfringens enteritis in piglets. Further work is required to confirm whether cpb2-carrying type A C. perfringens have a pathogenic role in enteric infection in neonatal swine.",,"['Farzan, Abdolvahab', 'Kircanski, Jasmina', 'DeLay, Josepha', 'Soltes, Glenn', 'Songer, J. Glenn', 'Friendship, Robert', 'Prescott, John F.']",,,,
,PMC,Respiratory disease outbreak in a veterinary hospital associated with canine parainfluenza virus infection,,PMC3524821,,,"A cluster of canine parainfluenza virus infections was identified in a veterinary referral hospital. While hospital-associated outbreaks of canine parainfluenza virus infection have not been previously reported, veterinary hospitals possess some of the same risk factors that may be present in traditional high-risk sites such as kennels. Hospital-associated transmission of canine respiratory pathogens, therefore, must be considered.",,"['Weese, J. Scott', 'Stull, Jason']",,,,
,PMC,Lung protection strategy as an effective treatment in acute respiratory distress syndrome,,PMC3762235,,,,,"['Jabbari, Ali', 'Alijanpour, Ebrahim', 'Amri Maleh, Parvize', 'Heidari, Behzad']",,,,
,PMC,Human Rhinoviruses,http://dx.doi.org/10.1128/CMR.00077-12,PMC3553670,,,"Human rhinoviruses (HRVs), first discovered in the 1950s, are responsible for more than one-half of cold-like illnesses and cost billions of dollars annually in medical visits and missed days of work. Advances in molecular methods have enhanced our understanding of the genomic structure of HRV and have led to the characterization of three genetically distinct HRV groups, designated groups A, B, and C, within the genus Enterovirus and the family Picornaviridae. HRVs are traditionally associated with upper respiratory tract infection, otitis media, and sinusitis. In recent years, the increasing implementation of PCR assays for respiratory virus detection in clinical laboratories has facilitated the recognition of HRV as a lower respiratory tract pathogen, particularly in patients with asthma, infants, elderly patients, and immunocompromised hosts. Cultured isolates of HRV remain important for studies of viral characteristics and disease pathogenesis. Indeed, whether the clinical manifestations of HRV are related directly to viral pathogenicity or secondary to the host immune response is the subject of ongoing research. There are currently no approved antiviral therapies for HRVs, and treatment remains primarily supportive. This review provides a comprehensive, up-to-date assessment of the basic virology, pathogenesis, clinical epidemiology, and laboratory features of and treatment and prevention strategies for HRVs.",,"['Jacobs, Samantha E.', 'Lamson, Daryl M.', 'St. George, Kirsten', 'Walsh, Thomas J.']",,,,
,PMC,Serologic Evidence of Pandemic Influenza Virus H1N1 2009 Infection in Cats in China,http://dx.doi.org/10.1128/CVI.00618-12,PMC3535780,,,"Infection of domestic cats with (H1N1) pandemic 2009 (pdm09) influenza A virus has recently been documented. In this paper, we report for the first time the sporadically current seroprevalence of (H1N1) pdm09 influenza A virus infection in cats in China. Thirteen of 1,080 sera were found positive by nucleoprotein (NP)-specific enzyme-linked immunosorbent assays (ELISAs) in different cat populations in southern China. It is very important to stress further surveillance of pandemic (H1N1) 2009 influenza A virus in cats in southern China.",,"['Su, Shuo', 'Yuan, Liguo', 'Li, Huatao', 'Chen, Jidang', 'Xie, Jiexiong', 'Huang, Zhen', 'Jia, Kun', 'Li, Shoujun']",,,,
,PMC,Tinkering with Translation: Protein Synthesis in Virus-Infected Cells,http://dx.doi.org/10.1101/cshperspect.a012351,PMC3579402,,,"Viruses are obligate intracellular parasites, and their replication requires host cell functions. Although the size, composition, complexity, and functions encoded by their genomes are remarkably diverse, all viruses rely absolutely on the protein synthesis machinery of their host cells. Lacking their own translational apparatus, they must recruit cellular ribosomes in order to translate viral mRNAs and produce the protein products required for their replication. In addition, there are other constraints on viral protein production. Crucially, host innate defenses and stress responses capable of inactivating the translation machinery must be effectively neutralized. Furthermore, the limited coding capacity of the viral genome needs to be used optimally. These demands have resulted in complex interactions between virus and host that exploit ostensibly virus-specific mechanisms and, at the same time, illuminate the functioning of the cellular protein synthesis apparatus.",,"['Walsh, Derek', 'Mathews, Michael B.', 'Mohr, Ian']",,,,
,PMC,Canonical and Non-Canonical Barriers Facing AntimiR Cancer Therapeutics,,PMC3901840,,,"Once considered genetic “oddities”, microRNAs (miRNAs) are now recognized as key epigenetic regulators of numerous biological processes, including some with a causal link to the pathogenesis, maintenance, and treatment of cancer. The crux of small RNA-based therapeutics lies in the antagonism of potent cellular targets; the main shortcoming of the field in general, lies in ineffective delivery. Inhibition of oncogenic miRNAs is a relatively nascent therapeutic concept, but as with predecessor RNA-based therapies, success hinges on delivery efficacy. This review will describe the canonical (e.g. pharmacokinetics and clearance, cellular uptake, endosome escape, etc.) and non-canonical (e.g. spatial localization and accessibility of miRNA, technical limitations of miRNA inhibition, off-target impacts, etc.) challenges to the delivery of antisense-based anti-miRNA therapeutics (i.e. antimiRs) for the treatment of cancer. Emphasis will be placed on how the current leading antimiR platforms—ranging from naked chemically modified oligonucleotides to nanoscale delivery vehicles—are affected by and overcome these barriers. The perplexity of antimiR delivery presents both engineering and biological hurdles that must be overcome in order to capitalize on the extensive pharmacological benefits of antagonizing tumor-associated miRNAs",,"['Cheng, Christopher J.', 'Saltzman, W. Mark', 'Slack, Frank J.']",,,,
,PMC,DEUBIQUITINATING ENZYMES AS PROMISING DRUG TARGETS FOR INFECTIOUS DISEASES,,PMC5485257,,,"Deubiquitinating enzymes (DUBs) remove ubiquitin and ubiquitin-like modifications from proteins and they have been known to contribute to processes relevant in microbial infection, such as immune responses pathways. Numerous viral and bacterial DUBs have been identified, and activities of several host DUBs are known to be modulated during the infection process, either by a pathogen or by a host. Recently there have been attempts to take advantage of this feature and design therapeutic inhibitors of DUBs that can be used to limit the spread of infection. This review is focused on exploring the potential of DUBs in the treatment of infectious diseases.",,"['Nanduri, Bindu', 'Suvarnapunya, Akamol E.', 'Venkatesan, Malabi', 'Edelmann, Mariola J.']",,,,
,PMC,Targeting the ubiquitin-mediated proteasome degradation of p53 for cancer therapy,,PMC3637405,,,"Within the past decade, there has been a revolution in the types of drugs developed to treat cancer. Therapies that selectively target cancer-specific aberrations, such as kinase inhibitors, have made a dramatic impact on a subset of patients. In spite of these successes, there is still a dearth of treatment options for the vast majority of patients. Therefore, there is a need to design therapies with broader efficacy. The p53 tumor suppressor pathway is one of the most frequently altered in human cancers. However, about half of all cancers retain wild-type p53, yet through various mechanisms, the p53 pathway is otherwise inactivated. Targeting this pathway for reactivation truly represents the “holy grail” in cancer treatment. Most commonly, destabilization of p53 by various components of ubiquitin-proteasome system, notably the ubiquitin ligase MDM2 and its partner MDMX as well as various deubiquitinating enzymes (DUBs), render p53 inert and unresponsive to stress signals. Reinstating its function in cancer has been a long sought-after goal. Towards this end, a great deal of work has been devoted to the development of compounds that either interfere with the p53-MDM2 and p53-MDMX interactions, inhibit MDM2 E3 activity, or target individual DUBs. Here we review the current progress that has been made in the field, with a special emphasis on both MDM2 and DUB inhibitors. Developing inhibitors targeting the upstream of the p53 ubiquitination pathway will likely also be a valuable option.",,"['DeVine, Tiffany', 'Dai, Mu-Shui']",,,,
,PMC,Experimental vaccines against potentially pandemic and highly pathogenic avian influenza viruses,http://dx.doi.org/10.2217/fvl.12.122,PMC3579652,,,"Influenza A viruses continue to emerge and re-emerge, causing outbreaks, epidemics and occasionally pandemics. While the influenza vaccines licensed for public use are generally effective against seasonal influenza, issues arise with production, immunogenicity, and efficacy in the case of vaccines against pandemic and emerging influenza viruses, and highly pathogenic avian influenza virus in particular. Thus, there is need of improved influenza vaccines and vaccination strategies. This review discusses advances in alternative influenza vaccines, touching briefly on licensed vaccines and vaccine antigens; then reviewing recombinant subunit vaccines, virus-like particle vaccines and DNA vaccines, with the main focus on virus-vectored vaccine approaches.",,"['Mooney, Alaina J', 'Tompkins, S Mark']",,,,
,PMC,Metallo-β-lactamase 1 - why blame New Delhi & India?,,PMC3657891,23481076,CC BY-NC-SA,,2013 Jan,"Mohapatra, Prasanta Raghab",Indian J Med Res,,,
,PMC,A longitudinal study about the effect of practicing Yan Xin Qigong on medical care cost with medical claims data,,PMC4330469,,,"We use 7-year longitudinal medical claims data and statistical models to study the relationship between practicing Yan Xin Qigong (YXQG), a traditional advanced Chinese Qigong that has been integrated with modern science and technology, and practitioners’ medical care utilization and the associated costs. We find that for the sampled practitioners, their average monthly medical visits and the associated costs are significantly lower after practicing YXQG. After controlling for other factors, the longer of practicing YXQG, the more likely there was a fall in average medical visits and medical costs. The main findings are robust to various estimation methods.",,"['Yan, Xin', 'Shen, Hua', 'Loh, Charles', 'Shao, Jianzhong', 'Yang, Yuhong', 'Lu, Chunling']",,,,
,PMC,"Clinical Application of a Multiplex Real-Time PCR Assay for Simultaneous Detection of Legionella Species, Legionella pneumophila, and Legionella pneumophila Serogroup 1",http://dx.doi.org/10.1128/JCM.02510-12,PMC3536254,,,"We developed a single-tube multiplex real-time PCR assay capable of simultaneously detecting and discriminating Legionella spp., Legionella pneumophila, and Legionella pneumophila serogroup 1 in primary specimens. Evaluation of 21 clinical specimens and 115 clinical isolates demonstrated this assay to be a rapid, high-throughput diagnostic test with 100% specificity that may aid during legionellosis outbreaks and epidemiologic investigations.",,"['Benitez, Alvaro J.', 'Winchell, Jonas M.']",,,,
,PMC,Clinical Accuracy of a PLEX-ID Flu Device for Simultaneous Detection and Identification of Influenza Viruses A and B,http://dx.doi.org/10.1128/JCM.01978-12,PMC3536229,,,"Respiratory tract infections caused by influenza A and B viruses often present nonspecifically, and a rapid, high-throughput laboratory technique that can identify influenza viruses is clinically and epidemiologically desirable. The PLEX-ID Flu assay (Abbott Molecular Inc., Des Plaines, IL) incorporates multilocus PCR and electrospray ionization-mass spectrometry to detect and differentiate influenza A 2009 H1N1 (H1N1-p), seasonal H1N1 (H1N1-s), influenza A H3N2, and influenza B viruses in nasopharyngeal swab (NPS) specimens. The clinical performance characteristics of the PLEX-ID Flu assay in symptomatic patients were determined in this multicenter trial. A total of 2,617 prospectively and retrospectively collected NPS specimens from patients with influenza-like illness between February 2008 and 28 May 2010 were eligible for inclusion in the study. Each specimen was tested in parallel by the PLEX-ID Flu assay and by the Prodesse ProFLU+ assay (Prodesse Inc., Madison, WI), to detect influenza A and B viruses. Specimens testing positive for influenza A virus by ProFLU+ were subtyped as H1N1-p, H1N1-s, or H3N2 by using the ProFAST+ assay (Gen-Probe Prodesse Inc.). The reproducibility of the PLEX-ID Flu assay ranged from 98.3 to 100.0%, as determined by testing a nine-specimen panel at three clinical sites on each of 5 days. Positive percent agreements (PPAs) and negative percent agreements (NPAs) of the PLEX-ID Flu assay were 94.5% and 99.0% for influenza A virus and 96.0% and 99.9% for influenza B virus, respectively. For the influenza A virus subtyping characterization, the PLEX-ID Flu assay had PPAs and NPAs of 98.3% and 97.5% for H1N1-p, 88.6% and 100.0% for H1N1-s, and 98.0% and 99.9% for H3N2, respectively. The overall agreements between the PLEX-ID and Prodesse ProFLU+/ProFAST+ assays were 97.1 to 100.0%. Bidirectional Sanger sequencing analysis revealed that 87.5% of 96 discrepant results between the PLEX-ID Flu and ProFLU+/ProFAST+ assays were found upon influenza A virus detection and H1N1-p subtyping. The PLEX-ID Flu assay demonstrated a high level of accuracy for the simultaneous detection and identification of influenza A and B viruses in patient specimens, providing a new laboratory tool for the rapid diagnosis and management of influenza A and B virus infections.",,"['Tang, Yi-Wei', 'Lowery, Kristin S.', 'Valsamakis, Alexandra', 'Schaefer, Virginia C.', 'Chappell, James D.', 'White-Abell, Jill', 'Quinn, Criziel D.', 'Li, Haijing', 'Washington, Cicely A.', 'Cromwell, Jenna', 'Giamanco, Chantel M.', 'Forman, Michael', 'Holden, Jeffery', 'Rothman, Richard E.', 'Parker, Michelle L.', 'Ortenberg, Elaine V.', 'Zhang, Lei', 'Lin, Yea-Lin', 'Gaydos, Charlotte A.']",,,,
,PMC,European Surveillance for Pantropic Canine Coronavirus,http://dx.doi.org/10.1128/JCM.02466-12,PMC3536214,,,"Highly virulent pantropic canine coronavirus (CCoV) strains belonging to subtype IIa were recently identified in dogs. To assess the distribution of such strains in Europe, tissue samples were collected from 354 dogs that had died after displaying systemic disease in France (n = 92), Hungary (n = 75), Italy (n = 69), Greece (n = 87), The Netherlands (n = 27), Belgium (n = 4), and Bulgaria (n = 1). A total of 124 animals tested positive for CCoV, with 33 of them displaying the virus in extraintestinal tissues. Twenty-four CCoV strains (19.35% of the CCoV-positive dogs) detected in internal organs were characterized as subtype IIa and consequently assumed to be pantropic CCoVs. Sequence and phylogenetic analyses of the 5′ end of the spike protein gene showed that pantropic CCoV strains are closely related to each other, with the exception of two divergent French viruses that clustered with enteric strains.",,"['Decaro, Nicola', 'Cordonnier, Nathalie', 'Demeter, Zoltan', 'Egberink, Herman', 'Elia, Gabriella', 'Grellet, Aurélien', 'Le Poder, Sophie', 'Mari, Viviana', 'Martella, Vito', 'Ntafis, Vasileios', 'von Reitzenstein, Marcela', 'Rottier, Peter J.', 'Rusvai, Miklos', 'Shields, Shelly', 'Xylouri, Eftychia', 'Xu, Zach', 'Buonavoglia, Canio']",,,,
,PMC,Self-Collection of Foam Nasal Swabs for Respiratory Virus Detection by PCR among Immunocompetent Subjects and Hematopoietic Cell Transplant Recipients,http://dx.doi.org/10.1128/JCM.02871-12,PMC3536199,,,"Self-collected foam nasal swabs (NS) obtained after instillation of saline spray were compared with nasal washes from immunocompetent subjects during 146 upper respiratory infections (URIs); the sensitivities for reverse transcription (RT)-PCR respiratory virus detection were 95% and 88%, respectively (P = 0.06). The sensitivities from NS collected with and without saline spray during 142 URIs from immunocompetent subjects were 96% and 86% (P = 0.004), respectively, and those from 140 URI samples from hematopoietic cell transplantation recipients were 88% and 85% (P = 0.56), respectively.",,"['Campbell, Angela P.', 'Kuypers, Jane', 'Englund, Janet A.', 'Guthrie, Katherine A.', 'Corey, Lawrence', 'Boeckh, Michael']",,,,
,PMC,"Molecular Characterization of a Respiratory Syncytial Virus Outbreak in a Hematology Unit in Heidelberg, Germany",http://dx.doi.org/10.1128/JCM.02151-12,PMC3536189,,,"In 2011 and 2012, a large outbreak of respiratory syncytial virus (RSV) infections affecting 57 laboratory-confirmed patients occurred in an adult hematology unit in Heidelberg, Germany. During the outbreak investigation, we performed molecular genotyping of RSV strains to differentiate between single versus multiple introductions of the virus into the unit. Furthermore, we assessed the time of viral shedding of consecutive samples from the patients in order to better understand the possible impact of prolonged shedding for outbreak control management. We used subtype-specific reverse transcription-PCR on nasopharyngeal and bronchoalveolar specimens for routine diagnostics and for measuring the viral shedding period. Samples of 47 RSV-infected patients involved in the outbreak were genotyped by sequence analysis and compared to samples from RSV-infected hospitalized children representing the timing of the annual RSV epidemic in the community. Molecular investigation of the virus strains from clinical samples revealed a unique cluster with identical nucleotide sequences of RSV type A (RSV A outbreak strain) for 41 patients, while 3 patients were infected with different RSV A (nonoutbreak) strains and three other patients with RSV type B. Outbreak strains were identified in samples from November 2011 until January 2012, while nonoutbreak strains were from samples coinciding with the community epidemic in February and March 2012. Median duration of viral shedding time was 24.5 days (range, 1 to 168 days) with no difference between outbreak and nonoutbreak strains (P = 0.45). Our investigation suggests a single introduction of the RSV A outbreak strain into the unit that spread among the immunocompromised patients. Prolonged viral shedding may have contributed to nosocomial transmission and should be taken into account in the infection control management of RSV outbreaks in settings with heavily immunosuppressed patients.",,"['Geis, Steffen', 'Prifert, Christiane', 'Weissbrich, Benedikt', 'Lehners, Nicola', 'Egerer, Gerlinde', 'Eisenbach, Christoph', 'Buchholz, Udo', 'Aichinger, Elisabeth', 'Dreger, Peter', 'Neben, Kai', 'Burkhardt, Ulrich', 'Ho, Anthony D.', 'Kräusslich, Hans-Georg', 'Heeg, Klaus', 'Schnitzler, Paul']",,,,
,PMC,Human Papillomavirus Type 16 E6/E7-Specific Cytotoxic T Lymphocytes for Adoptive Immunotherapy of HPV-Associated Malignancies,http://dx.doi.org/10.1097/CJI.0b013e318279652e,PMC3521877,,,"Vaccines prevent HPV-associated cancer but, although these tumors express foreign, viral antigens (E6 and E7 proteins), they have little benefit in established malignancies, likely due to negative environmental cues that block tumor recognition and induce T cell anergy in vivo. We postulated that we could identify mechanisms by which ex vivo stimulation of T cells could reactivate and expand tumor-directed T-cell lines from HPV-positive cancer patients for subsequent adoptive immunotherapy. A total of 68 patients with HPV-associated cancers were studied. Peripheral blood T cells were stimulated with monocyte-derived dendritic cells loaded with pepmixes (peptide libraries of 15-mers overlapping by 11 amino-acids) spanning E6/E7, in the presence or absence of specific accessory cytokines. The resulting T-cell lines were further expanded with pepmix-loaded activated B-cell blasts. IFNγ release and cytotoxic responses to E6/E7 were assessed. We successfully reactivated and expanded (>1200-fold) E6/E7-specific T cells from 8/16 cervical and 33/52 oropharyngeal cancer patients. The presence of the cytokines IL-6, -7, -12 and -15 is critical for this process. These T cell lines possess the desirable characteristics of polyclonality, multiple T-cell subset representation (including the memory compartment) and a T(H)1 bias, and may eliminate E6/E7-positive targets. In conclusion, we have shown it is possible to robustly generate HPV16 E6/E7-directed T-cell lines from patients with HPV16-associated cancers. Because our technique is scalable and good-manufacturing-procedures compliant, these lines could be used for adoptive cellular immunotherapy of patients with HPV16-positive cancers.",,"['Ramos, Carlos A.', 'Narala, Neeharika', 'Vyas, Gayatri M.', 'Leen, Ann M.', 'Gerdemann, Ulrike', 'Sturgis, Erich M.', 'Anderson, Matthew L.', 'Savoldo, Barbara', 'Heslop, Helen E.', 'Brenner, Malcolm K.', 'Rooney, Cliona M.']",,,,
,PMC,Infectious diseases citation patterns: mapping the literature 2008–2010,http://dx.doi.org/10.3163/1536-5050.101.1.009,PMC3543135,,,"OBJECTIVES: The research identified the publication types and ages most frequently cited in the infectious diseases literature and the most commonly cited journals. METHODS: From 2008–2010, 5,056 articles in 5 infectious diseases journals cited 166,650 items. Two random samples were drawn: one (n = 1,060) from the total set of citations and one (n = 1,060) from the citations to journal articles. For each sample citation, publication type and date, age of cited item, and inclusion of uniform resource locator (URL) were collected. For each item in the cited journal articles sample, journal title, publication date, and age of the cited article were collected. Bradford zones were used for further analysis. RESULTS: Journal articles (91%, n = 963) made up the bulk of cited items, followed by miscellaneous items (4.6%, n = 49). Dates of publication for cited items ranged from 1933–2010 (mean = 2001, mode = 2007). Over half (50.2%, n = 483) of cited journal articles were published within the previous 5 years. The journal article citations included 358 unique journal titles. DISCUSSION: The citations to current and older publications in a range of disciplines, heavy citation of journals, and citation of miscellaneous and government documents revealed the depth and breadth of resources needed for the study of infectious diseases.",,"['Rethlefsen, Melissa L.', 'Livinski, Alicia A.']",,,,
,PMC,Inhibition of Tulane Virus Replication in vitro with RNA Interference,http://dx.doi.org/10.1002/jmv.23340,PMC3508507,,,"RNA interference (RNAi), a conserved mechanism triggered by small interfering RNA (siRNA), has been used for suppressing gene expression through RNA degradation. The replication of caliciviruses (CVs) with RNAi was studied using the Tulane virus (TV) as a model. Five siRNAs targeting the non-structural, the major (VP1) and minor (VP2) structural genes of the TV were developed and the viruses were quantified using qPCR and TCID(50) assay. Treatment of the cells with siRNA 4 hours before viral inoculation significantly reduced viral titer by up to 2.6 logs and dramatically decreased viral RNA copy numbers and viral titers 48 hours post infection in four of the five siRNAs studied. The results were confirmed by Western blot, in which the major structural protein VP1 was markedly reduced in both the cells and the culture medium. Two small protein bands of the S and P domains of the viral capsid protein were also detected in the cell lysates, although their role in viral replication remains unknown. Since the TV shares many biological properties with human noroviruses (NoVs), the successful demonstration of RNAi in TV replication would provide valuable information in control of acute gastroenteritis caused by human NoVs.",,"['Fan, Qiang', 'Wei, Chao', 'Xia, Ming', 'Jiang, Xi']",,,,
,PMC,Oral presentation in dengue hemorrhagic fever: A rare entity,http://dx.doi.org/10.4103/0976-9668.107324,PMC3633297,23633881,CC BY-NC-SA,"One of the major health hazards which is prevalent and dangerous is the dengue fever which causes the death of many people. This may be associated with a variety of mucocutaneous manifestations which may be of help in early diagnosis. Many biochemical assays and hematological investigations may aid in the further diagnosis and treatment of the fatal disease. Oral lesions are rare to occur and if present, are often mistaken for platelet abnormality. This case report highlights the importance of oral lesions and it is the first of its kind to be reported as dengue hemorrhagic fever.",2013 Jan-Jun,"['Mithra, R.', 'Baskaran, Pavitra', 'Sathyakumar, M.']",J Nat Sci Biol Med,,,
,PMC,The Use of Respirators to Reduce Inhalation of Airborne Biological Agents,http://dx.doi.org/10.1080/15459624.2013.799964,PMC4670234,,,,,"['Janssen, Larry', 'Ettinger, Harry', 'Graham, Stephan', 'Shaffer, Ronald', 'Zhuang, Ziqing']",,,,
,PMC,Acute demyelinating encephalomyelitis: Clinical characteristics and outcome,http://dx.doi.org/10.4103/1817-1745.111418,PMC3680891,23772240,CC BY-NC-SA,"BACKGROUND: ADEM, although relatively uncommon, is probably under-recognized. OBJECTIVES: To spotlight the clinical profile and therapeutic outcome of children with ADEM. MATERIALS AND METHODS: This is a prospective study of patients with ADEM who were admitted to the Pediatric Departments in Aladan and Alfarawanya Hospitals in Kuwait, from January 2009 to January 2011. Clinical, microbiological and radiological data were analyzed. RESULTS: Of 48 patients presented with acute neurological symptoms and signs, 21 patients fulfilled criteria for ADEM. 80.95% of cases were presenting in winter and spring, 57% of patients had a history of upper respiratory tract illness. The commonest presentations were motor deficits, convulsions and altered consciousness. CSF virology studies showed herpes simplex virus (HSV) and Epstein-Barr virus (EBV) (3 patients) whereas nasal and nasopharyngeal swab showed evidence of influenza H1N1 virus (1 patient). Brain MRI was performed in all patients and revealed multiple hyperintense supratentorial brain lesions on T2/FLAIR images. 85.7% of patients had cortical and/or subcortical white matter lesions which were bilateral and asymmetric in location and size. CONCLUSION: ADEM although rare must be considered in children with acute onset of neurological signs and symptoms and must be distinguished from any acute neurological insult.",2013 Jan-Apr,"['Elhassanien, Ahmed Farag', 'Aziz, Hesham Abdel']",J Pediatr Neurosci,,,
,PMC,A study of non-prescription usage of antibiotics in the upper respiratory tract infections in the urban population,http://dx.doi.org/10.4103/0976-500X.107687,PMC3643347,23662028,CC BY-NC-SA,,2013 Jan-Mar,"Bhanwra, Sangeeta",J Pharmacol Pharmacother,,,
,PMC,INDOOR AIR QUALITY AND THERMAL COMFORT—RESULTS OF A PILOT STUDY IN ELDERLY CARE CENTERS IN PORTUGAL,http://dx.doi.org/10.1080/15287394.2013.757213,PMC4269561,,,"The age of the European population is rising and percentage of adults aged 65 years and older is projected to increase from 16% in 2000 to 20% in 2020. It has been estimated that older subjects spend approximately 19 to 20 h/d indoors. Older individuals may be particularly at risk for detrimental effects from pollutants, even at low concentrations, due to reduced immunological defenses and multiple underlying chronic diseases. Six Porto, Portugal, urban area elderly care centers (ECC), housing a total of 425 older persons, were studied to assess indoor air quality (IAQ) and thermal comfort (TC) in two seasons. This study presents the IAQ and TC results in 36 rooms and constitutes part of a wider and ongoing study. The study areas were all naturally ventilated, and indoor concentrations in winter were within Portuguese reference values. However, 42% of the participants were dissatisfied with indoor thermal conditions, rating it “slightly cool.” In summer, the index rate of dissatisfied individuals was lower (8%). Significant differences were found between seasons in predicted percent of dissatisfied people (PPD) and predicted mean vote (PMV) indices. Fungal concentrations frequently exceeded reference levels (>500 colony-forming units [CFU]/m(3)). In addition, other pollutants occasionally exceeded reference levels. To our knowledge, this is the first study in Portugal to assess effects of indoor air contaminants on the health status and quality of life in older subjects living in ECC. Although IAQ and TC parameters were mostly within reference values, the results suggest a need to improve the balance between IAQ and TC in ECC, a critical environment housing a susceptible population.",,"['Mendes, Ana', 'Pereira, Cristiana', 'Mendes, Diana', 'Aguiar, Lívia', 'Neves, Paula', 'Silva, Susana', 'Batterman, Stuart', 'Teixeira, João Paulo']",,,,
,PMC,AMP-Activated Protein Kinase Is Required for the Macropinocytic Internalization of Ebolavirus,http://dx.doi.org/10.1128/JVI.01634-12,PMC3554099,,,"Identification of host factors that are needed for Zaire Ebolavirus (EBOV) entry provides insights into the mechanism(s) of filovirus uptake, and these factors may serve as potential antiviral targets. In order to identify novel host genes and pathways involved in EBOV entry, gene array findings in the National Cancer Institute's NCI-60 panel of human tumor cell lines were correlated with permissivity for EBOV glycoprotein (GP)-mediated entry. We found that the gene encoding the γ2 subunit of AMP-activated protein kinase (AMPK) strongly correlated with EBOV transduction in the tumor panel. The AMPK inhibitor compound C inhibited infectious EBOV replication in Vero cells and diminished EBOV GP-dependent, but not Lassa fever virus GPC-dependent, entry into a variety of cell lines in a dose-dependent manner. Compound C also prevented EBOV GP-mediated infection of primary human macrophages, a major target of filoviral replication in vivo. Consistent with a role for AMPK in filovirus entry, time-of-addition studies demonstrated that compound C abrogated infection when it was added at early time points but became progressively less effective when added later. Compound C prevented EBOV pseudovirion internalization at 37°C as cell-bound particles remained susceptible to trypsin digestion in the presence of the inhibitor but not in its absence. Mouse embryonic fibroblasts lacking the AMPKα1 and AMPKα2 catalytic subunits were significantly less permissive to EBOV GP-mediated infection than their wild-type counterparts, likely due to decreased macropinocytic uptake. In total, these findings implicate AMPK in macropinocytic events needed for EBOV GP-dependent entry and identify a novel cellular target for new filoviral antivirals.",,"['Kondratowicz, Andrew S.', 'Hunt, Catherine L.', 'Davey, Robert A.', 'Cherry, Sara', 'Maury, Wendy J.']",,,,
,PMC,Increasing Expression of MicroRNA 181 Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication and Has Implications for Controlling Virus Infection,http://dx.doi.org/10.1128/JVI.02386-12,PMC3554091,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important viral pathogens in the swine industry. Emerging evidence indicates that the host microRNAs (miRNAs) are involved in host-pathogen interactions. However, whether host miRNAs can target PRRSV and be used to inhibit PRRSV infection has not been reported. Recently, microRNA 181 (miR-181) has been identified as a positive regulator of immune response, and here we report that miR-181 can directly impair PRRSV infection. Our results showed that delivered miR-181 mimics can strongly inhibit PRRSV replication in vitro through specifically binding to a highly (over 96%) conserved region in the downstream of open reading frame 4 (ORF4) of the viral genomic RNA. The inhibition of PRRSV replication was specific and dose dependent. In PRRSV-infected Marc-145 cells, the viral mRNAs could compete with miR-181-targeted sequence in luciferase vector to interact with miR-181 and result in less inhibition of luciferase activity, further demonstrating the specific interactions between miR-181 and PRRSV RNAs. As expected, miR-181 and other potential PRRSV-targeting miRNAs (such as miR-206) are expressed much more abundantly in minimally permissive cells or tissues than in highly permissive cells or tissues. Importantly, highly pathogenic PRRSV (HP-PRRSV) strain-infected pigs treated with miR-181 mimics showed substantially decreased viral loads in blood and relief from PRRSV-induced fever compared to negative-control (NC)-treated controls. These results indicate the important role of host miRNAs in modulating PRRSV infection and viral pathogenesis and also support the idea that host miRNAs could be useful for RNA interference (RNAi)-mediated antiviral therapeutic strategies.",,"['Guo, Xue-kun', 'Zhang, Qiong', 'Gao, Li', 'Li, Ning', 'Chen, Xin-xin', 'Feng, Wen-hai']",,,,
,PMC,Macropinocytosis-Like HIV-1 Internalization in Macrophages Is CCR5 Dependent and Leads to Efficient but Delayed Degradation in Endosomal Compartments,http://dx.doi.org/10.1128/JVI.01802-12,PMC3554056,,,"HIV-1 endocytosis by a macropinocytosis-like mechanism has been shown to lead to productive infection in macrophages. However, little is known of this pathway. In this study, we examined HIV-1 endocytosis using biochemical approaches and imaging techniques in order to better understand the mechanisms that allow for productive infection of these cells via the endosomal pathway. We show here that this macropinocytosis-like mechanism is not the sole pathway involved in HIV-1 endocytosis in macrophages. However, this pathway specifically requires CCR5 engagement at the cell surface, which in turn suggests that the virus and its coreceptor are present in the endosomal environment simultaneously. Furthermore, although we observed efficient viral degradation following endocytosis, analyses of HIV-1 transport through the endolysosomal pathway revealed that viral degradation is delayed following endosomal internalization, possibly allowing the virus to complete its fusion.",,"['Gobeil, Lise-Andrée', 'Lodge, Robert', 'Tremblay, Michel J.']",,,,
,PMC,Japanese Encephalitis Virus Core Protein Inhibits Stress Granule Formation through an Interaction with Caprin-1 and Facilitates Viral Propagation,http://dx.doi.org/10.1128/JVI.02186-12,PMC3536427,,,"Stress granules (SGs) are cytoplasmic foci composed of stalled translation preinitiation complexes induced by environmental stress stimuli, including viral infection. Since viral propagation completely depends on the host translational machinery, many viruses have evolved to circumvent the induction of SGs or co-opt SG components. In this study, we found that expression of Japanese encephalitis virus (JEV) core protein inhibits SG formation. Caprin-1 was identified as a binding partner of the core protein by an affinity capture mass spectrometry analysis. Alanine scanning mutagenesis revealed that Lys(97) and Arg(98) in the α-helix of the JEV core protein play a crucial role in the interaction with Caprin-1. In cells infected with a mutant JEV in which Lys(97) and Arg(98) were replaced with alanines in the core protein, the inhibition of SG formation was abrogated, and viral propagation was impaired. Furthermore, the mutant JEV exhibited attenuated virulence in mice. These results suggest that the JEV core protein circumvents translational shutoff by inhibiting SG formation through an interaction with Caprin-1 and facilitates viral propagation in vitro and in vivo.",,"['Katoh, Hiroshi', 'Okamoto, Toru', 'Fukuhara, Takasuke', 'Kambara, Hiroto', 'Morita, Eiji', 'Mori, Yoshio', 'Kamitani, Wataru', 'Matsuura, Yoshiharu']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.03141-12,PMC3536421,,,,,,,,,
,PMC,Induction of Stress Granule-Like Structures in Vesicular Stomatitis Virus-Infected Cells,http://dx.doi.org/10.1128/JVI.02305-12,PMC3536414,,,"Previous studies from our laboratory revealed that cellular poly(C) binding protein 2 (PCBP2) downregulates vesicular stomatitis virus (VSV) gene expression. We show here that VSV infection induces the formation of granular structures in the cytoplasm containing cellular RNA-binding proteins, including PCBP2, T-cell-restricted intracellular antigen 1 (TIA1), and TIA1-related protein (TIAR). Depletion of TIA1 via small interfering RNAs (siRNAs), but not depletion of TIAR, results in enhanced VSV growth and gene expression. The VSV-induced granules appear to be similar to the stress granules (SGs) generated in cells triggered by heat shock or oxidative stress but do not contain some of the bona fide SG markers, such as eukaryotic initiation factor 3 (eIF3) or eIF4A, or the processing body (PB) markers, such as mRNA-decapping enzyme 1A (DCP1a), and thus may not represent canonical SGs or PBs. Our results revealed that the VSV-induced granules, called SG-like structures here, contain the viral replicative proteins and RNAs. The formation and maintenance of the SG-like structures required viral replication and ongoing protein synthesis, but an intact cytoskeletal network was not necessary. These results suggest that cells respond to VSV infection by aggregating the antiviral proteins, such as PCBP2 and TIA1, to form SG-like structures. The functional significance of these SG-like structures in VSV-infected cells is currently under investigation.",,"['Dinh, Phat X.', 'Beura, Lalit K.', 'Das, Phani B.', 'Panda, Debasis', 'Das, Anshuman', 'Pattnaik, Asit K.']",,,,
,PMC,Deep RNA Sequencing Reveals Complex Transcriptional Landscape of a Bat Adenovirus,http://dx.doi.org/10.1128/JVI.02332-12,PMC3536413,,,"Bat adenoviruses are a group of recently identified adenoviruses (AdVs) which are highly prevalent in bats yet share low similarity to known AdVs from other species. In this study, deep RNA sequencing was used to analyze the transcriptome at five time points following the infection of a bat AdV in a kidney cell line derived from a myotis bat species. Evidence of AdV replication was observed with the proportion of viral RNAs ranging from 0.01% at 6 h to 1.3% at 18 h. Further analysis of viral temporal gene expression revealed three replication stages, the early-stage genes encoding mainly host interaction proteins, the intermediate-stage genes for the DNA replication and assembly proteins, and the late-stage genes for most structural proteins. Several bat AdV genes were expressed at stages that differed from those of their counterpart genes previously reported for human AdV type 2. In addition, single-base resolution splice sites of several genes and promoter regions of all 30 viral genes were fully determined. Simultaneously, the temporal cellular gene expression profiles were identified. The most overrepresented functional categories of the differentially expressed genes were related to cellular immune response, transcription, translation, and DNA replication and repair. Taken together, the deep RNA sequencing provided a global, transcriptional profile of the novel bat AdV and the virus-host interactions which will be useful for the understanding and investigation of AdV replication, pathogenesis, and specific virus-bat interactions in future research.",,"['Wu, Lijun', 'Zhou, Peng', 'Ge, Xingyi', 'Wang, Lin-Fa', 'Baker, Michelle L.', 'Shi, Zhengli']",,,,
,PMC,Long-Distance RNA-RNA Interactions in the Coronavirus Genome Form High-Order Structures Promoting Discontinuous RNA Synthesis during Transcription,http://dx.doi.org/10.1128/JVI.01782-12,PMC3536410,,,"Coronavirus (CoV) transcription requires a high-frequency recombination process that links newly synthesized minus-strand subgenomic RNA copies to the leader region, which is present only once, at the 5′ end of the genome. This discontinuous RNA synthesis step is based on the complementarity between the transcription-regulating sequences (TRSs) at the leader region and those preceding each gene in the nascent minus-strand RNA. Furthermore, the template switch requires the physical proximity of RNA genome domains located between 20,000 and 30,000 nucleotides apart. In this report, it is shown that the efficacy of this recombination step is promoted by novel additional long-distance RNA-RNA interactions between RNA motifs located close to the TRSs controlling the expression of each gene and their complementary sequences mapping close to the 5′ end of the genome. These interactions would bring together the motifs involved in the recombination process. This finding indicates that the formation of high-order RNA structures in the CoV genome is necessary to control the expression of at least the viral N gene. The requirement of these long-distance interactions for transcription was shown by the engineering of CoV replicons in which the complementarity between the newly identified sequences was disrupted. Furthermore, disruption of complementarity in mutant viruses led to mutations that restored complementarity, wild-type transcription levels, and viral titers by passage in cell cultures. The relevance of these high-order structures for virus transcription is reinforced by the phylogenetic conservation of the involved RNA motifs in CoVs.",,"['Mateos-Gomez, Pedro A.', 'Morales, Lucia', 'Zuñiga, Sonia', 'Enjuanes, Luis', 'Sola, Isabel']",,,,
,PMC,Molecular Requirements for T Cell Recognition of N-Myristoylated Peptides Derived from the Simian Immunodeficiency Virus Nef Protein,http://dx.doi.org/10.1128/JVI.02142-12,PMC3536395,,,"We have recently isolated a rhesus macaque cytotoxic T cell line, 2N5.1, that specifically recognizes an N-myristoylated 5-mer peptide (C(14)-Gly-Gly-Ala-Ile-Ser [C14nef5]) derived from the simian immunodeficiency virus (SIV) Nef protein. Such C14nef5-specific T cells expand in the circulation of SIV-infected monkeys, underscoring the capacity of T cells to recognize viral lipopeptides; however, the molecular basis for the lipopeptide antigen presentation remains to be elucidated. Here, functional studies indicated that the putative antigen-presenting molecule for 2N5.1 was likely to have two separate antigen-binding sites, one for interaction with a C(14)-saturated acyl chain and the other for anchorage of the C-terminal serine residue. Mutants with alanine substitutions for the second glycine residue and the fourth isoleucine residue were not recognized by 2N5.1 but interfered with the presentation of C14nef5 to 2N5.1, indicating that these structural analogues retained the ability to interact with the antigen-presenting molecules. In contrast to the highly specific recognition of C14nef5 by 2N5.1, an additional cytotoxic T cell line, SN45, established independently from a C14nef5-stimulated T cell culture, showed superb reactivity to both C14nef5 and an N-myristoylated Nef 4-mer peptide, and therefore, the C-terminal serine residue was dispensable for the recognition of lipopeptides by the SN45 T cells. Furthermore, the mutants with alanine substitutions were indeed recognized by the SN45 T cells. Given that N-myristoylation of the Nef protein occurs in the conserved motifs and is critical for viral pathogenesis, these observations predict that the lipopeptide-specific T cell response is difficult for viruses to avoid by simply introducing amino acid mutations.",,"['Morita, Daisuke', 'Yamamoto, Yukie', 'Suzuki, Juri', 'Mori, Naoki', 'Igarashi, Tatsuhiko', 'Sugita, Masahiko']",,,,
,PMC,Exceptional Simian Hemorrhagic Fever Virus Diversity in a Wild African Primate Community,http://dx.doi.org/10.1128/JVI.02433-12,PMC3536393,,,Simian hemorrhagic fever virus (SHFV) is an arterivirus that causes severe disease in captive macaques. We describe two new SHFV variants subclinically infecting wild African red-tailed guenons (Cercopithecus ascanius). Both variants are highly divergent from the prototype virus and variants infecting sympatric red colobus (Procolobus rufomitratus). All known SHFV variants are monophyletic and share three open reading frames not present in other arteriviruses. Our data suggest a need to modify the current arterivirus classification.,,"['Lauck, Michael', 'Sibley, Samuel D.', 'Hyeroba, David', 'Tumukunde, Alex', 'Weny, Geoffrey', 'Chapman, Colin A.', 'Ting, Nelson', 'Switzer, William M.', 'Kuhn, Jens H.', 'Friedrich, Thomas C.', ""O'Connor, David H."", 'Goldberg, Tony L.']",,,,
,PMC,Cleavage of the Junin Virus Nucleoprotein Serves a Decoy Function To Inhibit the Induction of Apoptosis during Infection,http://dx.doi.org/10.1128/JVI.01929-12,PMC3536391,,,"The regulation of apoptosis during infection is an important factor for host survival and, in some cases, also for the virus life cycle. At the same time, mechanisms to prevent the induction of apoptosis have been observed in numerous viral pathogens, but until now the role of apoptosis during arenavirus infection has not been investigated. Junin virus (JUNV) belongs to the New World arenavirus serogroup of the Arenaviridae and is the causative agent of Argentine hemorrhagic fever. We have demonstrated that infection with JUNV in cell culture does not induce apoptosis but leads to cleavage of the nucleoprotein (NP) into discrete products resembling caspase cleavage events. Similar specific NP degradation patterns were also observed in NP-transfected cell lines, and a closer examination of the sequence of NP showed several putative caspase cleavage motifs. Point mutations that abolished these cleavage motifs were consistent with the loss of certain cleavage products. Consistent with these data, further studies showed that treatment with a caspase inhibitor also reduced NP cleavage, indicating that the observed cleavage events were occurring as a result of caspase activity with NP as a substrate. Finally, we showed that expression of NP suppresses the cleavage of caspase 3 in cells treated with an apoptosis activator. Based on these findings, we propose that NP functions as a decoy substrate for caspase cleavage in order to inhibit the induction of apoptosis in JUNV-infected cells.",,"['Wolff, Svenja', 'Becker, Stephan', 'Groseth, Allison']",,,,
,PMC,ADP Ribosylation Factor 1 Plays an Essential Role in the Replication of a Plant RNA Virus,http://dx.doi.org/10.1128/JVI.02383-12,PMC3536388,,,"Eukaryotic positive-strand RNA viruses replicate using the membrane-bound replicase complexes, which contain multiple viral and host components. Virus infection induces the remodeling of intracellular membranes. Virus-induced membrane structures are thought to increase the local concentration of the components that are required for replication and provide a scaffold for tethering the replicase complexes. However, the mechanisms underlying virus-induced membrane remodeling are poorly understood. RNA replication of red clover necrotic mosaic virus (RCNMV), a positive-strand RNA plant virus, is associated with the endoplasmic reticulum (ER) membranes, and ER morphology is perturbed in RCNMV-infected cells. Here, we identified ADP ribosylation factor 1 (Arf1) in the affinity-purified RCNMV RNA-dependent RNA polymerase fraction. Arf1 is a highly conserved, ubiquitous, small GTPase that is implicated in the formation of the coat protein complex I (COPI) vesicles on Golgi membranes. Using in vitro pulldown and bimolecular fluorescence complementation analyses, we showed that Arf1 interacted with the viral p27 replication protein within the virus-induced large punctate structures of the ER membrane. We found that inhibition of the nucleotide exchange activity of Arf1 using the inhibitor brefeldin A (BFA) disrupted the assembly of the viral replicase complex and p27-mediated ER remodeling. We also showed that BFA treatment and the expression of dominant negative Arf1 mutants compromised RCNMV RNA replication in protoplasts. Interestingly, the expression of a dominant negative mutant of Sar1, a key regulator of the biogenesis of COPII vesicles at ER exit sites, also compromised RCNMV RNA replication. These results suggest that the replication of RCNMV depends on the host membrane traffic machinery.",,"['Hyodo, Kiwamu', 'Mine, Akira', 'Taniguchi, Takako', 'Kaido, Masanori', 'Mise, Kazuyuki', 'Taniguchi, Hisaaki', 'Okuno, Tetsuro']",,,,
,PMC,A Chimeric Vesiculo/Alphavirus Is an Effective Alphavirus Vaccine,http://dx.doi.org/10.1128/JVI.01860-12,PMC3536361,,,"While a large number of mosquito-transmitted alphaviruses are known to cause serious human diseases, there are no licensed vaccines that protect against alphavirus infections. The alphavirus chikungunya virus (CHIKV) has caused multiple recent outbreaks of chikungunya fever. This virus has the potential to cause a worldwide epidemic and has generated strong interest in development of a prophylactic CHIKV vaccine. We report here on the development of a potent experimental vaccine for CHIKV based on a chimeric vesicular stomatitis virus (VSV) expressing the entire CHIKV envelope polyprotein (E3-E2-6K-E1) in place of the VSV glycoprotein (G). These VSVΔG-CHIKV chimeras incorporated functional CHIKV glycoproteins into the viral envelope in place of VSV G. The chimeric viruses were attenuated for growth in tissue culture but could be propagated to high titers without VSV G complementation. They also generated robust neutralizing antibody and cellular immune responses to CHIKV in mice after a single dose and protected mice against CHIKV infection. VSVΔG-alphavirus chimeras could have general applicability as alphavirus vaccines.",,"['Chattopadhyay, Anasuya', 'Wang, Eryu', 'Seymour, Robert', 'Weaver, Scott C.', 'Rose, John K.']",,,,
,PMC,Recommendations for Biomonitoring of Emergency Responders: Focus on Occupational Health Investigations and Occupational Health Research,,PMC4501486,,,"The disaster environment frequently presents rapidly evolving and unpredictable hazardous exposures to emergency responders. Improved estimates of exposure and effect from biomonitoring can be used to assess exposure–response relationships, potential health consequences, and effectiveness of control measures. Disaster settings, however, pose significant challenges for biomonitoring. A decision process for determining when to conduct biomonitoring during and following disasters was developed. Separate but overlapping decision processes were developed for biomonitoring performed as part of occupational health investigations that directly benefit emergency responders in the short term and for biomonitoring intended to support research studies. Two categories of factors critical to the decision process for biomonitoring were identified: Is biomonitoring appropriate for the intended purpose and is biomonitoring feasible under the circumstances of the emergency response? Factors within these categories include information needs, relevance, interpretability, ethics, methodology, and logistics. Biomonitoring of emergency responders can be a valuable tool for exposure and risk assessment. Information needs, relevance, and interpretability will largely determine if biomonitoring is appropriate; logistical factors will largely determine if biomonitoring is feasible. The decision process should be formalized and may benefit from advance planning.",,"['Decker, John A.', 'DeBord, D. Gayle', 'Bernard, Bruce', 'Dotson, G. Scott', 'Halpin, John', 'Hines, Cynthia J.', 'Kiefer, Max', 'Myers, Kyle', 'Page, Elena', 'Schulte, Paul', 'Snawder, John']",,,,
,PMC,Comparing lignocaine-adrenaline-tetracaine gel with lignocaine infiltration for anesthesia during repair of lacerations: A randomized trial,http://dx.doi.org/10.5847/wjem.j.issn.1920-8642.2013.04.007,PMC4129907,,,"BACKGROUND: This study aimed to compare the topical anesthetic lignocaine, adrenaline, and tetracaine (LAT) (4% lignocaine, 1:2 000 adrenaline, 1% tetracaine) with the conventional lignocaine infiltration(LI) for repair of minor lacerations, for the comfort of anesthetic administration, efficacy, adverse effects and cost. METHODS: This was a prospective randomized clinical trial. Forty Asian patients who required toilet and suture for minor lacerations in the emergency department of the Singapore General Hospital over a 4-month period. The patients were assigned randomly to 2 arms of treatment. The first was the LAT gel group who had LAT gel applied to the laceration prior to suturing. The second was the control group in whom the anesthetic administered was lignocaine infiltration (LI) via a syringe. The pain of the process of administering anesthetic and efficacy of anesthesia were scored using the visual pain scale included within. The efficacy of LAT vs. lignocaine infiltration as an anesthetic prior to the toilet and suture of minor lacerations and complications of therapy. RESULTS: Twenty patients were randomized to LAT gel and 16 to LI on an intention to treat analysis. The mean pain score by patients in the LAT gel group was 2.5 (0.52 SE), and 2.5 (0.58 SE) in the LI group. The pain score for pain during application of the anesthetic was 1.5 (0.40) in the LAT gel group, and 3.5 (0.46) in the LI group. There was no difference in complications between the LAT and LI groups CONCLUSION: LAT gel prior to the toilet and suture of minor lacerations is proven to be as efficacious as LI in terms of patient comfort and effectiveness of anesthesia. The complications are also comparable to those treated with LI.",,"['Lee, Jean MH', 'Laxmikantha, Nina', 'Ong, Marcus E H', 'Wong, Evelyn', 'Wee, Jeremy CP']",,,,
,PMC,What can we predict about viral evolution and emergence?,http://dx.doi.org/10.1016/j.coviro.2012.12.003,PMC3626763,,,"Predicting the emergence of infectious diseases has been touted as one of the most important goals of biomedical science, with an array of funding schemes and research projects. However, evolutionary biology generally has a dim view of prediction, and there is a danger that erroneous predictions will mean a misuse of resources and undermine public confidence. Herein, I outline what can be realistically predicted about viral evolution and emergence, argue that any success in predicting what may emerge is likely to be limited, but that forecasting how viruses might evolve and spread following emergence is more tractable. I also emphasize that a properly grounded research program in disease prediction must involve a synthesis of ecological and genetic perspectives.",,"Holmes, Edward C.",,,,
,PMC,Antivirals in seasonal and pandemic influenza—future perspectives,http://dx.doi.org/10.1111/irv.12049,PMC5978628,,,"Please cite this paper as: Wathen et al. (2012) Antivirals in seasonal and pandemic influenza—future perspectives. Influenza and Other Respiratory Viruses 7(Suppl. 1), 76–80. Antiviral drugs continue to be an important option for the treatment of influenza disease and will likely be the only option during the early phases of pandemic. However, the limited number of drug classes licensed for treatment of influenza raises several issues, particularly in the face of drug resistance. Two classes of drugs are presently licensed for treatment of influenza, M2 and neuraminidase inhibitors. M2 inhibitors are currently not recommended for treatment of influenza because of widespread resistance and resistance to neuraminidase inhibitors has been observed during the past influenza seasonal outbreaks. Additional antiviral drugs with novel mechanisms of action are clearly needed for the treatment of influenza. Fortunately, the landscape of drugs in early and advanced development has dramatically increased over the last 5 years. Drugs targeting viral functions such as attachment, entry/fusion, transcription, and polymerase and drugs targeting host factors affecting viral replication are currently in clinical trials. Examples of these novel antiviral drugs and the challenges for influenza antiviral drug development are discussed in this article.",,"['Wathen, Michael W.', 'Barro, Mario', 'Bright, Rick A.']",,,,
,PMC,Interplay between viruses and host mRNA degradation,http://dx.doi.org/10.1016/j.bbagrm.2012.12.003,PMC3632658,,,"Messenger RNA degradation is a fundamental cellular process that plays a critical role in regulating gene expression by controlling both the quality and the abundance of mRNAs in cells. Naturally, viruses must successfully interface with the robust cellular RNA degradation machinery to achieve an optimal balance between viral and cellular gene expression and establish a productive infection in the host. In the past several years, studies have discovered many elegant strategies that viruses have evolved to circumvent the cellular RNA degradation machinery, ranging from disarming the RNA decay pathways and co-opting the factors governing cellular mRNA stability to promoting host mRNA degradation that facilitates selective viral gene expression and alters the dynamics of host-pathogen interaction. This review summarizes the current knowledge of the multifaceted interaction between viruses and cellular mRNA degradation machinery to provide an insight into the regulatory mechanisms that influence gene expression in viral infections.",,"['Narayanan, Krishna', 'Makino, Shinji']",,,,
,PMC,Reprogramming cellular events by poly(ADP-ribose)-binding proteins,http://dx.doi.org/10.1016/j.mam.2012.12.005,PMC3812366,,,"Poly(ADP-ribosyl)ation is a posttranslational modification catalyzed by the poly(ADP-ribose) polymerases (PARPs). These enzymes covalently modify glutamic, aspartic and lysine amino acid side chains of acceptor proteins by the sequential addition of ADP-ribose (ADPr) units. The poly(ADP-ribose) (pADPr) polymers formed alter the physico-chemical characteristics of the substrate with functional consequences on its biological activities. Recently, non-covalent binding to pADPr has emerged as a key mechanism to modulate and coordinate several intracellular pathways including the DNA damage response, protein stability and cell death. In this review, we describe the basis of non-covalent binding to pADPr that has led to the emerging concept of pADPr-responsive signaling pathways. This review emphasizes the structural elements and the modular strategies developed by pADPr-binding proteins to exert a fine-tuned control of a variety of pathways. Poly(ADP-ribosyl)ation reactions are highly regulated processes, both spatially and temporally, for which at least four specialized pADPr-binding modules accommodate different pADPr structures and reprogram protein functions. In this review, we highlight the role of well-characterized and newly discovered pADPr-binding modules in a diverse set of physiological functions.",,"['Krietsch, Jana', 'Rouleau, Michèle', 'Pic, Émilie', 'Ethier, Chantal', 'Dawson, Ted M.', 'Dawson, Valina L.', 'Masson, Jean-Yves', 'Poirier, Guy G.', 'Gagné, Jean-Philippe']",,,,
,PMC,STRUCTURAL AND BIOCHEMICAL BASIS FOR THE DIFFERENCE IN THE HELICASE ACTIVITY OF TWO DIFFERENT CONSTRUCTS OF SARS-COV HELICASE,,PMC3612351,,,"The non-structural protein 13 (nsp13) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is a helicase that separates double-stranded RNA or DNA with a 5’-3’ polarity, using the energy of nucleotide hydrolysis. We have previously determined the minimal mechanism of helicase function by nsp13 where we demonstrated that the enzyme unwinds nucleic acid in discrete steps of 9.3 base-pairs each with a catalytic rate of 30 steps per second. In that study we used different constructs of nsp13 (GST and H(6) constructs). GST-nsp13 showed much more efficient nucleic acid unwinding than the H(6)-tagged counterpart. At 0.1 second, more than 50% of the ATP is hydrolyzed hydrolysed by GST-nsp13 compared to less than 5% ATP hydrolysis by H(6)-nsp13. Interestingly, the two constructs have the same binding affinity for nucleic acids. We, therefore propose that the difference in the catalytic efficiency of these two constructs is due to the interference of ATP binding by the histidine tag at the amino-terminus of nsp13.",,"['Adedeji, Adeyemi O.', 'Singh, Kamalendra', 'Sarafianos, Stefan G.']",,,,
,PMC,Customized Siderocalins for Host Defense and Beyond,http://dx.doi.org/10.1016/j.cbpa.2012.11.014,PMC3634885,,,"Bacterial pathogens use siderophores to obtain iron from the host in order to survive and grow. The host defends against siderophore-mediated iron acquisition by producing siderocalins. Siderocalins are a siderophore binding subset of the lipocalin family of proteins. The design of the siderophore binding pocket gives siderocalins the ability to bind a wide variety of siderophores and protect the host against several pathogens. Siderocalins have been identified in humans, chickens, and quail, among other animals. The differences in the respective siderocalins suggest that each was developed in response to the most serious pathogens encountered by that animal. Additionally, siderocalins have been observed in many roles unrelated to pathogen defense including differentiation, embryogenesis, inflammation, and cancer.",,"['Sia, Allyson K.', 'Allred, Benjamin E.', 'Raymond, Kenneth N.']",,,,
,PMC,Bacterial and viral interactions within the nasopharynx contribute to the risk of acute otitis media,http://dx.doi.org/10.1016/j.jinf.2012.12.002,PMC3571106,,,"SUMMARY OBJECTIVES: To understand relationships between microbes in pathogenesis of acute otitis media during respiratory tract infections, we compared nasopharyngeal bacteria and respiratory viruses in symptomatic children with and without AOM. METHODS: We enrolled children (6–35 months) with acute symptoms suggestive of AOM and analyzed their nasopharyngeal samples for bacteria by culture and for 15 respiratory viruses by PCR. Non-AOM group had no abnormal otoscopic signs or only middle ear effusion, while AOM group showed middle ear effusion and acute inflammatory signs in pneumatic otoscopy along with acute symptoms. RESULTS: Of 505 children, the non-AOM group included 187 and the AOM group 318. One or more bacterial AOM pathogen (Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis) was detected in 78% and 96% of the non-AOM and AOM group, respectively (P < .001). Colonization with S. pneumoniae and H. influenzae, each alone, increased risk of AOM (odds ratio (OR) 2.92; 95% confidence interval (CI), .91–9.38, and 5.13; 1.36–19.50, respectively) and co-colonization with M. catarrhalis further increased risk (OR 4.36; 1.46–12.97, and 9.00; 2.05–39.49, respectively). Respiratory viruses were detected in 90% and 87% of the non-AOM and AOM group, respectively. RSV was significantly associated with risk of AOM without colonization by bacterial AOM pathogens (OR 6.50; 1.21–34.85). CONCLUSIONS: Co-colonization by M. catarrhalis seems to increase risk of AOM and RSV may contribute to AOM pathogenesis even without nasopharyngeal bacterial colonization.",,"['Ruohola, Aino', 'Pettigrew, Melinda M.', 'Lindholm, Laura', 'Jalava, Jari', 'Räisänen, Kati S.', 'Vainionpää, Raija', 'Waris, Matti', 'Tähtinen, Paula A.', 'Laine, Miia K.', 'Lahti, Elina', 'Ruuskanen, Olli', 'Huovinen, Pentti']",,,,
,PMC,The lipid kinase PI4KIIIβ preserves lysosomal identity,http://dx.doi.org/10.1038/emboj.2012.341,PMC3567500,,,"Lipid modifications are essential in cellular sorting and trafficking inside cells. The role of phosphoinositides in trafficking between Golgi and endocytic/lysosomal compartments has been extensively explored and the kinases responsible for these lipid changes have been identified. In contrast, the mechanisms that mediate exit and recycling from lysosomes (Lys), considered for a long time as terminal compartments, are less understood. In this work, we identify a dynamic association of the lipid kinase PI4KIIIβ with Lys and unveil its regulatory function in lysosomal export and retrieval. We have found that absence of PI4KIIIβ leads to abnormal formation of tubular structures from the lysosomal surface and loss of lysosomal constituents through these tubules. We demonstrate that the kinase activity of PI4KIIIβ is necessary to prevent this unwanted lysosomal efflux under normal conditions, and to facilitate proper sorting when recycling of lysosomal material is needed, such as in the physiological context of lysosomal reformation after prolonged starvation.",,"['Sridhar, Sunandini', 'Patel, Bindi', 'Aphkhazava, David', 'Macian, Fernando', 'Santambrogio, Laura', 'Shields, Dennis', 'Cuervo, Ana Maria']",,,,
,PMC,Targeting virulence mechanisms for the prevention and therapy of arenaviral hemorrhagic fever,http://dx.doi.org/10.1016/j.antiviral.2012.12.003,PMC3563861,,,"A number of arenaviruses are pathogenic for humans, but they differ significantly in virulence. Lassa virus, found in West Afri ca, causes severe hemorrhagic fever (HF), while the other principal Old World arenavirus, lymphocytic choriomeningitis virus, causes mild illness in persons with normal immune function, and poses a threat only to immunocompromised individuals. The New World agents, including Junin, Machupo and Sabia virus, are highly pathogenic for humans. Arenaviral HF is characterized by high viremia and general immune suppression, the mechanism of which is unknown. Studies using viral reverse genetics, cell-based assays, animal models and human genome-wide association analysis have revealed potential mechanisms by which arenaviruses cause severe disease in humans. Each of the four viral gene products (GPC, L polymerase, NP, and Z matrix protein) and several host-cell factors (e.g., α-dystroglycan) are responsible for mediating viral entry, genome replication, and the inhibition of apoptosis, translation and interferon-beta (IFNβ) production. This review summarizes current knowledge of the role of each viral protein and host factor in the pathogenesis of arenaviral HF. Insights from recent studies are being exploited for the development of novel therapies.",,"['McLay, Lisa', 'Ansari, Aftab', 'Liang, Yuying', 'Ly, Hinh']",,,,
,PMC,Staufen2 functions in Staufen1-mediated mRNA decay by binding to itself and its paralog and promoting UPF1 helicase but not ATPase activity,http://dx.doi.org/10.1073/pnas.1213508110,PMC3545820,,,"Staufen (STAU)1-mediated mRNA decay (SMD) is a posttranscriptional regulatory mechanism in mammals that degrades mRNAs harboring a STAU1-binding site (SBS) in their 3′-untranslated regions (3′ UTRs). We show that SMD involves not only STAU1 but also its paralog STAU2. STAU2, like STAU1, is a double-stranded RNA-binding protein that interacts directly with the ATP-dependent RNA helicase up-frameshift 1 (UPF1) to reduce the half-life of SMD targets that form an SBS by either intramolecular or intermolecular base-pairing. Compared with STAU1, STAU2 binds ∼10-fold more UPF1 and ∼two- to fivefold more of those SBS-containing mRNAs that were tested, and it comparably promotes UPF1 helicase activity, which is critical for SMD. STAU1- or STAU2-mediated augmentation of UPF1 helicase activity is not accompanied by enhanced ATP hydrolysis but does depend on ATP binding and a basal level of UPF1 ATPase activity. Studies of STAU2 demonstrate it changes the conformation of RNA-bound UPF1. These findings, and evidence for STAU1−STAU1, STAU2−STAU2, and STAU1−STAU2 formation in vitro and in cells, are consistent with results from tethering assays: the decrease in mRNA abundance brought about by tethering siRNA-resistant STAU2 or STAU1 to an mRNA 3′ UTR is inhibited by downregulating the abundance of cellular STAU2, STAU1, or UPF1. It follows that the efficiency of SMD in different cell types reflects the cumulative abundance of STAU1 and STAU2. We propose that STAU paralogs contribute to SMD by “greasing the wheels” of RNA-bound UPF1 so as to enhance its unwinding capacity per molecule of ATP hydrolyzed.",,"['Park, Eonyoung', 'Gleghorn, Michael L.', 'Maquat, Lynne E.']",,,,
,PMC,Fat chance! Getting a grip on a slippery modification,http://dx.doi.org/10.1021/cb300607e,PMC3693556,,,"Protein palmitoylation describes the post-translational fatty acyl thioesterification of cellular cysteine residues, and is critical for the localization, trafficking, and compartmentalization of a large number of membrane proteins. This labile thioester modification facilitates a dynamic acylation cycle that directionally traffics key signaling complexes, receptors, and channels to select membrane compartments. Chemical enrichment and advanced mass spectrometry-based proteomics methods have highlighted a pervasive role for palmitoylation across all eukaryotes, including animals, plants, and parasites. Emerging chemical tools promise to open new avenues to study the enzymes, substrates, and dynamics of this distinct post-translational modification.",,"['Tom, Christopher M.B.', 'Martin, Brent R.']",,,,
,PMC,"Novel therapeutic vaccines [(HSP65 + IL-12)DNA-, granulysin- and Ksp37-vaccine] against tuberculosis and synergistic effects in the combination with chemotherapy",http://dx.doi.org/10.4161/hv.23230,PMC3891708,,,"Purpose: Multi-drug resistant tuberculosis (MDR-TB) and extremely drug resistant (XDR) TB are big problems in the world. We have developed novel TB therapeutic vaccines, HVJ-Envelope/HSP65 + IL-12 DNA vaccine (HSP65-vaccine), granulysin vaccine and killer specific secretory protein of 37kDa (Ksp37) vaccine. Methods and Results: HSP65 vaccine showed strong therapeutic effect against both MDR-TB and XDR-TB in mice. Intradermal immunization of HSP65-vaccine showed stronger therapeutic effect against TB than intramuscular or subcutaneous immunization. Furthermore, the synergistic therapeutic effect was observed when the vaccine was administrated in combination with Isoniazid (INH), which is a first line drug for chemotherapy. The combination of types of vaccines (HSP65- and granulysin- vaccines) also showed synergistic therapeutic effect. In the monkey model, granulysin-vaccine prolonged the survival period after the infection of TB and long-term survival was observed in vaccine-treated group. We examined the potential of two kinds of novel DNA vaccines (Ksp37-vaccine and granulysin-vaccine). Both vaccines augmented in vivo differentiation of CTL against TB. We measured the amount of Ksp37 protein in human serum and revealed that the level of Ksp37 protein of patients with tuberculosis was lower than that of healthy volunteers. Therefore, we established Ksp37 transgenic mice as well as granulysin transgenic mice to elucidate the function of those proteins. Both transgenic mice were resistant to TB infection. Conclusion: These data indicate the potential of combinational therapy; the combination of two DNA vaccines or combination of DNA vaccine with antibiotic drug. Thus, it will provide a novel strategy for the treatment of MDR-TB.",,"['Kita, Yoko', 'Hashimoto, Satomi', 'Nakajima, Toshihiro', 'Nakatani, Hitoshi', 'Nishimatsu, Shiho', 'Nishida, Yasuko', 'Kanamaru, Noriko', 'Kaneda, Yasuhumi', 'Takamori, Yasushi', 'McMurray, David', 'Tan, Esterlina V.', 'Cang, Marjorie L.', 'Saunderson, Paul', 'Dela Cruz, E.C.', 'Okada, Masaji']",,,,
,PMC,The broad-spectrum antiviral functions of IFIT and IFITM proteins,http://dx.doi.org/10.1038/nri3344,PMC3773942,,,"Over the past few years, several groups have identified novel genes downstream of type I interferon (IFN) signaling that inhibit infection by individual or multiple families of viruses. Among these IFN stimulated genes (ISGs) with antiviral activity are two genetically and functionally distinct families — IFN-induced proteins with tetratricopeptide repeats (IFIT) and IFN-induced transmembrane proteins (IFITM). This review focuses on recent advances in identifying the unique mechanisms of action of IFIT and IFITM genes, which explain their broad-spectrum activity against replication, spread, and disease pathogenesis of a range of human viruses.",,"['Diamond, Michael S.', 'Farzan, Michael']",,,,
,PMC,Evidences for the unfolding mechanism of three-dimensional domain swapping,http://dx.doi.org/10.1002/pro.2209,PMC3595458,,,"The full or partial unfolding of proteins is widely believed to play an essential role in three-dimensional domain swapping. However, there is little research that has rigorously evaluated the association between domain swapping and protein folding/unfolding. Here, we examined a kinetic model in which domain swapping occurred via the denatured state produced by the complete unfolding of proteins. The relationships between swapping kinetics and folding/unfolding thermodynamics were established, which were further adopted as criteria to show that the proposed mechanism dominates in three representative proteins: Cyanovirin-N (CV-N), the C-terminal domain of SARS-CoV main protease (M(pro)-C), and a single mutant of oxidized thioredoxin (Trx_W28A(ox)).",,"['Liu, Zhirong', 'Huang, Yongqi']",,,,
,PMC,IFITM1 is a tight junction protein that inhibits hepatitis C virus entry,http://dx.doi.org/10.1002/hep.26066,PMC3566288,,,"Type 1 interferon (IFN) continues to be the foundation for the current standard of care combination therapy for chronic hepatitis C virus (HCV) infection, yet the component interferon-stimulated genes (ISGs) that mediate the antiviral actions of IFN are not fully defined. Interferon-induced transmembrane protein 1 (IFITM1) is an ISG product that suppresses early stage infection by a number of viruses through an as yet unknown mechanism of action. Moreover, the actions of IFITM1 on HCV infection are not fully elucidated. Here we identify IFITM1 as a hepatocyte tight junction protein and a potent anti-HCV effector molecule. IFITM1 expression is induced early during IFN treatment of hepatocytes and accumulates at hepatic tight junctions in HCV-infected human patient liver during IFN therapy. Additionally, we found that IFITM1 interacts with HCV co-receptors including CD81 and occludin to disrupt the process of viral entry. Thus, IFITM1 is an anti-HCV ISG whose actions impart control of HCV infection through interruption of viral coreceptor function. CONCLUSION: This study defines IFITM1 as an ISG effector with action against HCV entry. Design of therapy regimens to enhance IFITM1 expression should improve the virologic response among HCV patients undergoing treatment with type I IFN.",,"['Wilkins, Courtney', 'Woodward, Jessica', 'Lau, Daryl T-Y', 'Barnes, Amy', 'Joyce, Michael', 'McFarlane, Nicola', 'McKeating, Jane', 'Tyrrell, D. Lorne', 'Gale, Michael']",,,,
,PMC,What is the Role of Respiratory Viruses in Community Acquired Pneumonia; What is the Best Therapy for Influenza and Other Viral Causes of CAP?,http://dx.doi.org/10.1016/j.idc.2012.11.007,PMC3572787,,,"Respiratory viruses including influenza have long been appreciated as a cause of community acquired pneumonia (CAP), particularly among children, people with serious medical co-morbidities and military recruits. They are increasingly recognized as a cause of CAP among adults, particularly older adults. Polymerase chain reaction-based testing has allowed detection of newer agents (e.g. human metapneumovirus, coronavirus HKU1 and NL63) as well as improved the ability to detect “old” viral infections such as influenza virus and rhinovirus. When PCR is used, viruses have been detected in 45–75% of children and 15–54% of adults with CAP. Co-infection with viruses and bacteria is common and it remains challenging to determine which patients have only viral infection as the cause of CAP. Treatment for influenza with neuraminidase inhibitors should be started promptly for patients with CAP when influenza is suspected or documented, regardless of evidence of bacterial co-infection. Better ways to diagnose viral CAP and to integrate detection into management are urgently needed, as well as better treatment options for non-influenza respiratory viral infections.",,"Pavia, Andrew T",,,,
,PMC,"Tackling animal diseases to protect human health: As veterinary science celebrates cattle plague eradication, the inextricable link between human, animal and ecosystem health is increasingly appreciated",http://dx.doi.org/10.1038/embor.2012.201,PMC3537153,,,"Veterinary research is gaining in importance not only because of the economic impact of animal diseases, but also because animals are a fertile reservoir of zoonoses; pathogens that could jump the species barrier and infect humans.",,"Rinaldi, Andrea",,,,
,PMC,Protecting society: Biological security and dual-use dilemma in the life sciences—status quo and options for the future,http://dx.doi.org/10.1038/embor.2012.195,PMC3537148,,,"Concerns over biosecurity remain unresolved, as the debate around the recent publications on human transmissible H5N1 flu demonstrated. A range of measures and the involvement of all stakeholders are needed to better protect society from malicious abuse of biological research.",,"['Uhlenhaut, Christine', 'Burger, Reinhard', 'Schaade, Lars']",,,,
,PMC,Mapping Inhibitor Binding Modes on an Active Cysteine Protease via NMR Spectroscopy,http://dx.doi.org/10.1021/bi301305k,PMC3566641,,,"Cruzain is a member of the papain/cathepsin-L family of cysteine proteases, and the major cysteine protease of the protozoan Trypanosoma cruzi, the causative agent of Chagas’ disease. We report an auto-induction methodology that provides soluble-cruzain at high yields (> 30 mg per liter in minimal media). These increased yields provide sufficient quantities of active enzyme for use in NMR-based ligand mapping. Using CD and NMR spectroscopy, we also examined the solution-state structural dynamics of the enzyme in complex with a covalently bound vinyl sulfone inhibitor (K777). We report the backbone amide and side chain carbon chemical shift assignments of cruzain in complex with K777. These resonance assignments were used to identify and map residues located in the substrate binding pocket, including the catalytic Cys25 and His162. Selective (15)N-Cys, (15)N-His, and (13)C-Met labeling was performed to quickly assess cruzain-ligand interactions for a set of eight low molecular weight compounds exhibiting micromolar binding or inhibition. Chemical shift perturbation mapping verifies that six of the eight compounds bind to cruzain at the active site. Three different binding modes were delineated for the compounds, namely covalent, non-covalent, and non-interacting. These results provide examples of how NMR spectroscopy can be used to screen compounds for fast evaluation of enzyme-inhibitor interactions in order to facilitate lead compound identification and subsequent structural studies.",,"['Lee, Gregory M.', 'Balouch, Eaman', 'Goetz, David H.', 'Lazic, Ana', 'McKerrow, James H.', 'Craik, Charles S.']",,,,
,PMC,Systematic annotation and analysis of “virmugens” - virulence factors whose mutants can be used as live attenuated vaccines,http://dx.doi.org/10.1016/j.vaccine.2012.11.066,PMC3556277,,,"Live attenuated vaccines are usually generated by mutation of genes encoding virulence factors. “Virmugen” is coined here to represent a gene that encodes for a virulent factor of a pathogen and has been proven feasible in animal models to make a live attenuated vaccine by knocking out this gene. Not all virulence factors are virmugens. VirmugenDB is a web-based virmugen database (http://www.violinet.org/virmugendb). Currently, VirmugenDB includes 225 virmugens that have been verified to be valuable for vaccine development against 57 bacterial, viral, and protozoan pathogens. Bioinformatics analysis has revealed significant patterns in virmugens. For example, 10 Gram-negative and one Gram-positive bacterial aroA genes are virmugens. A sequence analysis has revealed at least 50% of identities in the protein sequences of the 10 Gram-negative bacterial aroA virmugens. As a pathogen case study, Brucella virmugens were analyzed. Out of 15 verified Brucella virmugens, six are related to carbohydrate or nucleotide transport and metabolism, and two involving cell membrane biogenesis. In addition, 54 virmugens from 24 viruses and 12 virmugens from 4 parasites are also stored in VirmugenDB. Virmugens tend to involve metabolism of nutrients (e.g., amino acids, carbohydrates, and nucleotides) and cell membrane formation. Host genes whose expressions were regulated by virmugen mutation vaccines or wild type virulent pathogens have also been annotated and systematically compared. The bioinformatics annotation and analysis of virmugens helps elucidate enriched virmugen profiles and the mechanisms of protective immunity, and further supports rational vaccine design.",,"['Racz, Rebecca', 'Chung, Monica', 'Xiang, Zuoshuang', 'He, Yongqun']",,,,
,PMC,Systems approaches to influenza-virus host interactions and the pathogenesis of highly virulent and pandemic viruses,http://dx.doi.org/10.1016/j.smim.2012.11.001,PMC3596458,,,"Influenza virus research has recently undergone a shift from a virus-centric perspective to one that embraces the full spectrum of virus-host interactions and cellular signaling events that determine disease outcome. This change has been brought about by the increasing use and expanding scope of high-throughput molecular profiling and computational biology, which together fuel discovery in systems biology. In this review, we show how these approaches have revealed an uncontrolled inflammatory response as a contributor to the extreme virulence of the 1918 pandemic and avian H5N1 viruses, and how this response differs from that induced by the 2009 H1N1 viruses responsible for the most recent influenza pandemic. We also discuss how new animal models, such as the Collaborative Cross mouse systems genetics platform, are key to the necessary systematic investigation of the impact of host genetics on infection outcome, how genome-wide RNAi screens have identified hundreds of cellular factors involved in viral replication, and how systems biology approaches are making possible the rational design of new drugs and vaccines against an ever-evolving respiratory virus.",,"['Korth, Marcus J.', 'Tchitchek, Nicolas', 'Benecke, Arndt', 'Katze, Michael G.']",,,,
,PMC,Identification of avian RIG-I responsive genes during influenza infection,http://dx.doi.org/10.1016/j.molimm.2012.10.038,PMC3565471,,,"Ducks can survive infection with highly pathogenic avian influenza viruses that are lethal to chickens. We showed that the influenza detector, RIG-I, can initiate antiviral responses in ducks, but this gene is absent in chickens. We can reconstitute this pathway by transfecting chicken DF-1 embryonic fibroblast cells with duck RIG-I, which augments their antiviral response to influenza and decreases viral titre. However, the genes downstream of duck RIG-I that mediate this antiviral response to influenza are not known. Using microarrays, we compared the transcriptional profile of chicken embryonic fibroblasts transfected with duck RIG-I or empty vector, and infected with low or highly pathogenic avian influenza viruses. Transfected duck RIG-I expressed in chicken cells was associated with the marked induction of many antiviral innate immune genes upon infection with both viruses. We used real-time PCR to confirm upregulation of a subset of these antiviral genes including MX1, PKR, IFIT5, OASL, IFNB, and downregulation of the influenza matrix gene. These results provide some insight into the genes induced by duck RIG-I upon influenza infection, and provide evidence that duck RIG-I can function to elicit an interferon-driven, antiviral response against influenza in chicken embryonic fibroblasts.",,"['Barber, Megan RW', 'Aldridge, Jerry R', 'Fleming-Canepa, Ximena', 'Wang, Yong-Dong', 'Webster, Robert G', 'Magor, Katharine E']",,,,
,PMC,Cyclophilin 40 alters UVA-induced apoptosis and mitochondrial ROS generation in keratinocytes,http://dx.doi.org/10.1016/j.yexcr.2012.11.016,PMC3577976,,,"The CyP40 protein encoded by PPID gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. The CyP40 protein has been shown to possess PPIase activity and, similar to other family members, can bind to the immunosuppressant drug cyclosporin A (CsA). In this study, we created keratinocyte cell lines with CyP40 being stably knocked down using viral particles containing shRNA for CyP40 which knocked down the expression level of CyP40 transcripts by 90 to 99%. The proliferation rates of the cell lines with silenced CyP40 were decreased compared to the control cells. After UVA irradiation, the rate of apoptosis was found to be significantly lower in CyP40 silenced cell lines than it was in control cells. Moreover, mitochondrial membrane potential (MMP) was found to be less dissipated and mitochondrial permeability transition pore (MPTP) less active in cells with knocked down CyP40 than in control cells after UVA irradiation. Also, less mitochondrial superoxide was detected in the cells with silenced CyP40 compared to control cells after UVA exposure. Moreover, silencing of CyP40 partially modulates expression of key genes involved in mitochondrial pore formation including CyPD, ANTs and VDAC family members. The ability of CyP40 to regulate UV induced apoptosis implicates this protein as a potential target for therapy in cancer cells.",,"['Jandova, Jana', 'Janda, Jaroslav', 'Sligh, James E']",,,,
,PMC,Bacterial Resistance to Antisense Peptide Phosphorodiamidate Morpholino Oligomers,http://dx.doi.org/10.1128/AAC.00850-12,PMC3497173,,,"Peptide phosphorodiamidate morpholino oligomers (PPMOs) are synthetic DNA mimics that bind cRNA and inhibit bacterial gene expression. The PPMO (RFF)(3)RXB-AcpP (where R is arginine, F, phenylalanine, X is 6-aminohexanoic acid, B is β-alanine, and AcpP is acyl carrier protein) is complementary to 11 bases of the essential gene acpP (which encodes acyl carrier protein). The MIC of (RFF)(3)RXB-AcpP was 2.5 μM (14 μg/ml) in Escherichia coli W3110. The rate of spontaneous resistance of E. coli to (RFF)(3)RXB-AcpP was 4 × 10(−7) mutations/cell division. A spontaneous (RFF)(3)RXB-AcpP-resistant mutant (PR200.1) was isolated. The MIC of (RFF)(3)RXB-AcpP was 40 μM (224 μg/ml) for PR200.1. The MICs of standard antibiotics for PR200.1 and W3110 were identical. The sequence of acpP was identical in PR200.1 and W3110. PR200.1 was also resistant to other PPMOs conjugated to (RFF)(3)RXB or peptides with a similar composition or pattern of cationic and nonpolar residues. Genomic sequencing of PR200.1 identified a mutation in sbmA, which encodes an active transport protein. In separate experiments, a (RFF)(3)RXB-AcpP-resistant isolate (RR3) was selected from a transposome library, and the insertion was mapped to sbmA. Genetic complementation of PR200.1 or RR3 with sbmA restored susceptibility to (RFF)(3)RXB-AcpP. Deletion of sbmA caused resistance to (RFF)(3)RXB-AcpP. We conclude that resistance to (RFF)(3)RXB-AcpP was linked to the peptide and not the phosphorodiamidate morpholino oligomer, dependent on the composition or repeating pattern of amino acids, and caused by mutations in sbmA. The data further suggest that (RFF)(3)R-XB PPMOs may be transported across the plasma membrane by SbmA.",,"['Puckett, Susan E.', 'Reese, Kaleb A.', 'Mitev, Georgi M.', 'Mullen, Valerie', 'Johnson, Rudd C.', 'Pomraning, Kyle R.', 'Mellbye, Brett L.', 'Tilley, Lucas D.', 'Iversen, Patrick L.', 'Freitag, Michael', 'Geller, Bruce L.']",,,,
,PMC,Astrobiology Outreach and the Nature of Science: The Role of Creativity,http://dx.doi.org/10.1089/ast.2012.0873,PMC3698628,,,"There is concern in many developed countries that school students are turning away from science. However, students may be choosing not to study science and dismissing the possibility of a scientific career because, in the junior secondary years, they gain a false view of science and the work of scientists. There is a disparity between science as it is portrayed at school and science as it is practiced. This paper describes a study to explore whether engaging in science through astrobiology outreach activities may improve students' understanding of the nature and processes of science, and how this may influence their interest in a career in science. The results suggest that the students attending these Mars research–related outreach activities are more interested in science than the average student but are lacking in understanding of aspects of the nature of science. A significant difference was detected between pre- and posttest understandings of some concepts of the nature of science. Key Words: Science education—School science—Creativity—Nature and processes of science—Attitudes—Astrobiology. Astrobiology 12, 1143–1153.",,"['Fergusson, Jennifer', 'Oliver, Carol', 'Walter, Malcolm R.']",,,,
,PMC,Nasal cytokine responses to natural colds in asthmatic children,http://dx.doi.org/10.1111/cea.12005,PMC4219353,,,"BACKGROUND: The mechanisms by which viruses induce asthma exacerbations are not well-understood. OBJECTIVE: We characterized fluctuations in nasal aspirate cytokines during naturally-occurring respiratory viral infections in children with asthma. METHODS: Sixteen children underwent home collections of nasal aspirates when they were without cold symptoms and again during self-reported respiratory illnesses. The presence of viral infection was ascertained by multiplex PCR. Cytokines were measured by multiplex immune assay. mRNA expression for selected markers of viral infection was measured by RT-PCR. A cumulative respiratory symptom score was calculated for each day of measurement. Generalized estimated equations were used to evaluate associations between viral infection and marker elevation, and between marker elevation and symptom score. RESULTS: The 16 patients completed a total of 37 weeks of assessment (15 “well” weeks; 22 self-assessed “sick” weeks). Viral infections were detected in three of the “well” weeks and 17 of the “sick” weeks (10 rhinovirus, 3 coronavirus, 2 influenza A, 2 influenza B, 2 respiratory syncytial virus, 1 parainfluenza). Compared to virus-negative well weeks, nasal aspirate IFN-γ, CXCL8/IL-8, CXCL10/IP-10, CCL5/RANTES, CCL11/eotaxin-1, CCL2/MCP-1, CCL4/MIP-1β, CCL7/MCP-3 and CCL20/MIP3α protein levels increased during virus-positive sick weeks. Only a subset of cytokines (IFN-γ, CXCL8, CCL2, CCL4, CCL5 and CCL20) correlated with self-reported respiratory tract symptoms. While many aspirates were dilute and showed no mRNA signal, viral infection significantly increased the number of samples that were positive for IFN-λ1, IFN-λ2/3, TLR3, RIG-I and IRF7 mRNA. CONCLUSIONS & CLINICAL RELEVANCE: We conclude that, in children with asthma, naturally-occurring viral infections apparently induce a robust innate immune response including expression of specific chemokines, IFNs and IFN-responsive genes.",,"['Lewis, Toby C.', 'Henderson, Tiffany A.', 'Carpenter, Ashley R.', 'Ramirez, Ixsy A.', 'McHenry, Christina L.', 'Goldsmith, Adam M.', 'Ren, Xiaodan', 'Mentz, Graciela B.', 'Mukherjee, Bhramar', 'Robins, Thomas G.', 'Joiner, Terence A.', 'Mohammad, Layla S.', 'Nguyen, Emily R.', 'Burns, Mark A.', 'Burke, David T.', 'Hershenson, Marc B.']",,,,
,PMC,Viral–Bacterial Interactions in Acute Otitis Media,http://dx.doi.org/10.1007/s11882-012-0303-2,PMC3493715,,,"Acute otitis media (AOM) is a polymicrobial disease, which usually occurs as a complication of viral upper respiratory tract infection (URI). While respiratory viruses alone may cause viral AOM, they increase the risk of bacterial middle ear infection and worsen clinical outcomes of bacterial AOM. URI viruses alter Eustachian tube (ET) function via decreased mucociliary action, altered mucus secretion and increased expression of inflammatory mediators among other mechanisms. Transient reduction in protective functions of the ET allows colonizing bacteria of the nasopharynx to ascend into the middle ear and cause AOM. Advances in research help us to better understand the host responses to viral URI, the mechanisms of viral–bacterial interactions in the nasopharynx and the development of AOM. In this review, we present current knowledge regarding viral–bacterial interactions in the pathogenesis and clinical course of AOM. We focus on the common respiratory viruses and their established role in AOM.",,"['Marom, Tal', 'Nokso-Koivisto, Johanna', 'Chonmaitree, Tasnee']",,,,
,PMC,In Search of Cathepsins: How Reovirus Enters Host Cells,http://dx.doi.org/10.1089/dna.2012.1868,PMC3505829,,,"Encapsidated viruses bind cell surface receptors and enter through receptor-mediated endocytosis. The next step in infection requires uncoating of the virion. In this inaugural BIT, the role of proteases of the Cathepsin family, which are found endosomes, are critical for viral replication.",,"['Mainou, Bernardo A.', 'Dermody, Terence S.']",,,,
,PMC,Experimental and natural infections in MyD88- and IRAK-4-deficient mice and humans,http://dx.doi.org/10.1002/eji.201242683,PMC3752658,,,"Most Toll-like-receptors (TLRs) and interleukin-1 receptors (IL-1Rs) signal via myeloid differentiation primary response 88 (MyD88) and interleukin-1 receptor-associated kinase 4 (IRAK-4). The combined roles of these two receptor families in the course of experimental infections have been assessed in MyD88- and IRAK-4-deficient mice for almost fifteen years. These animals have been shown to be susceptible to 46 pathogens: 27 bacteria, 8 viruses, 7 parasites, and 4 fungi. Humans with inborn MyD88 or IRAK-4 deficiency were first identified in 2003. They suffer from naturally occurring life-threatening infections caused by a small number of bacterial species, although the incidence and severity of these infections decrease with age. Mouse TLR- and IL-1R-dependent immunity mediated by MyD88 and IRAK-4 seems to be vital to combat a wide array of experimentally administered pathogens at most ages. By contrast, human TLR- and IL-1R-dependent immunity mediated by MyD88 and IRAK-4 seems to be effective in the natural setting against only a few bacteria and is most important in infancy and early childhood. The roles of TLRs and IL-1Rs in protective immunity deduced from studies in mutant mice subjected to experimental infections should therefore be reconsidered in the light of findings for natural infections in humans carrying mutations as discussed in this review.",,"['von Bernuth, Horst', 'Picard, Capucine', 'Puel, Anne', 'Casanova, Jean-Laurent']",,,,
,PMC,Roadmap to developing a recombinant coronavirus S protein receptor-binding domain vaccine for severe acute respiratory syndrome,http://dx.doi.org/10.1586/erv.12.126,PMC3586247,,,"A subunit vaccine, RBD-S, is under development to prevent severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV), which is classified by the US NIH as a category C pathogen. This vaccine is comprised of a recombinant receptor-binding domain (RBD) of the SARS-CoV spike (S) protein and formulated on alum, together with a synthetic glucopyranosyl lipid A. The vaccine would induce neutralizing antibodies without causing Th2-type immunopathology. Vaccine development is being led by the nonprofit product development partnership; Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development in collaboration with two academic partners (the New York Blood Center and University of Texas Medical Branch); an industrial partner (Immune Design Corporation); and Walter Reed Army Institute of Research. A roadmap for the product development of the RBD-S SARS vaccine is outlined with a goal to manufacture the vaccine for clinical testing within the next 5 years.",,"['Jiang, Shibo', 'Bottazzi, Maria Elena', 'Du, Lanying', 'Lustigman, Sara', 'Tseng, Chien-Te Kent', 'Curti, Elena', 'Jones, Kathryn', 'Zhan, Bin', 'Hotez, Peter J']",,,,
,PMC,Cross-Allele Cytotoxic T Lymphocyte Responses against 2009 Pandemic H1N1 Influenza A Virus among HLA-A24 and HLA-A3 Supertype-Positive Individuals,http://dx.doi.org/10.1128/JVI.01841-12,PMC3503122,,,"Lack of a universal vaccine against all serotypes of influenza A viruses and recent progress on T cell-related vaccines against influenza A virus illuminate the important role of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes (CTLs) in anti-influenza virus immunity. However, the diverse HLA alleles among humans complicate virus-specific cellular immunity research, and elucidation of cross-HLA allele T cell responses to influenza virus specificity requires further detailed work. An ideal CTL epitope-based vaccine would cover a broad spectrum of epitope antigens presented by most, if not all, of the HLAs. Here, we evaluated the 2009 pandemic influenza A (H1N1) virus-specific T cell responses among the HLA-A24(+) population using a rationally designed peptide pool during the 2009 pandemic. Unexpectedly, cross-HLA allele T cell responses against the influenza A virus peptides were detected among both HLA-A11(+) and HLA-A24(+) donors. Furthermore, we found cross-responses in the entire HLA-A3 supertype population (including HLA-A11, -A31, -A33, and -A30). The cross-allele antigenic peptides within the peptide pool were identified and characterized, and the crystal structures of the major histocompatibility complex (MHC)-peptide complexes were determined. The subsequent HLA-A24-defined cross-allele peptides recognized by the HLA-A11(+) population were shown to mildly bind to the HLA-A*1101 molecule. Together with the structural models, these results partially explain the cross-allele responses. Our findings elucidate the promiscuity of the cross-allele T cell responses against influenza A viruses and are beneficial for the development of a T cell epitope-based vaccine applied in a broader population.",,"['Liu, Jun', 'Zhang, Shihong', 'Tan, Shuguang', 'Yi, Yong', 'Wu, Bin', 'Cao, Bin', 'Zhu, Fengcai', 'Wang, Chen', 'Wang, Hua', 'Qi, Jianxun', 'Gao, George F.']",,,,
,PMC,The N-Terminal Region of IFITM3 Modulates Its Antiviral Activity by Regulating IFITM3 Cellular Localization,http://dx.doi.org/10.1128/JVI.01828-12,PMC3503121,,,"Interferon-inducible transmembrane (IFITM) protein family members IFITM1, -2, and -3 restrict the infection of multiple enveloped viruses. Significant enrichment of a minor IFITM3 allele was recently reported for patients who were hospitalized for seasonal and 2009 H1N1 pandemic flu. This IFITM3 allele lacks the region corresponding to the first amino-terminal 21 amino acids and is unable to inhibit influenza A virus. In this study, we found that deleting this 21-amino-acid region relocates IFITM3 from the endosomal compartments to the cell periphery. This finding likely underlies the lost inhibition of influenza A virus that completes its entry exclusively within endosomes at low pH. Yet, wild-type IFITM3 and the mutant with the 21-amino-acid deletion inhibit HIV-1 replication equally well. Given the pH-independent nature of HIV-1 entry, our results suggest that IFITM3 can inhibit viruses that enter cells via different routes and that its N-terminal region is specifically required for controlling pH-dependent viruses.",,"['Jia, Rui', 'Pan, Qinghua', 'Ding, Shilei', 'Rong, Liwei', 'Liu, Shan-Lu', 'Geng, Yunqi', 'Qiao, Wentao', 'Liang, Chen']",,,,
,PMC,Complete Genome Sequence of a Vero Cell-Adapted Isolate of Porcine Epidemic Diarrhea Virus in Eastern China,http://dx.doi.org/10.1128/JVI.02674-12,PMC3503114,,,"In early 2012, a widespread porcine epidemic diarrhea virus (PEDV) occurred in eastern China. A cell-adapted isolate, SD-M, was at the four-passage level of virulent field strain SD, which was isolated from a 2-day-old dead suckling piglet that had suffered from severe diarrhea in Shandong Province, China. We report here the complete genome sequence of SD-M. This sequence will promote a better understanding of the molecular pathogenesis of PEDV.",,"['Zhao, Mengjiao', 'Sun, Zhen', 'Zhang, Yue', 'Wang, Guisheng', 'Wang, Hui', 'Yang, Fangfang', 'Tian, Fulin', 'Jiang, Shijin']",,,,
,PMC,Complete Genome Sequence of a Recombinant Nephropathogenic Infectious Bronchitis Virus Strain in China,http://dx.doi.org/10.1128/JVI.02575-12,PMC3503108,,,"Recently, nephropathogenic infectious bronchitis virus (IBV) outbreaks have occurred in commercial broiler flocks and have been associated with a high incidence and morbidity in China. The CK/CH/Zhejiang/06/10 strain (IBV-YX10) was isolated from a 12-day-old broiler chicken in a flock of chickens with swollen speckled kidneys and distended ureters filled with uric acid in China in 2010. Here we reported the complete genomic sequence of the IBV-YX10 which was a natural recombinant nephropathogenic infectious bronchitis virus strain. These findings will contribute additional insights into the molecular characteristics of evolving IBV genomes and the need for effective control of IBV in China.",,"['Xue, Yu', 'Xie, Qingmei', 'Yan, Zhuanqiang', 'Ji, Jun', 'Chen, Feng', 'Qin, Jianping', 'Sun, Baoli', 'Ma, Jingyun', 'Bi, Yingzuo']",,,,
,PMC,Critical Role for Interferon Regulatory Factor 3 (IRF-3) and IRF-7 in Type I Interferon-Mediated Control of Murine Norovirus Replication,http://dx.doi.org/10.1128/JVI.01824-12,PMC3503103,,,"Human noroviruses (HuNoV) are the major cause of epidemic, nonbacterial gastroenteritis in the world. The short course of HuNoV-induced symptoms has implicated innate immunity in control of norovirus (NoV) infection. Studies using murine norovirus (MNV) confirm the importance of innate immune responses during NoV infection. Type I alpha and beta interferons (IFN-α/β) limit HuNoV replicon function, restrict MNV replication in cultured cells, and control MNV replication in vivo. Therefore, the cell types and transcription factors involved in antiviral immune responses and IFN-α/β-mediated control of NoV infection are important to define. We used mice with floxed alleles of the IFNAR1 chain of the IFN-α/β receptor to identify cells expressing lysozyme M or CD11c as cells that respond to IFN-α/β to restrict MNV replication in vivo. Furthermore, we show that the transcription factors IRF-3 and IRF-7 work in concert to initiate unique and overlapping antiviral responses to restrict MNV replication in vivo. IRF-3 and IRF-7 restrict MNV replication in both cultured macrophages and dendritic cells, are required for induction of IFN-α/β in macrophages but not dendritic cells, and are dispensable for the antiviral effects of IFN-α/β that block MNV replication. These studies suggest that expression of the IFN-α/β receptor on macrophages/neutrophils and dendritic cells, as well as of IRF-3 and IRF-7, is critical for innate immune responses to NoV infection.",,"['Thackray, Larissa B.', 'Duan, Erning', 'Lazear, Helen M.', 'Kambal, Amal', 'Schreiber, Robert D.', 'Diamond, Michael S.', 'Virgin, Herbert W.']",,,,
,PMC,Complete Genome Sequence of an Infectious Bronchitis Virus Chimera between Cocirculating Heterotypic Strains,http://dx.doi.org/10.1128/JVI.02722-12,PMC3503099,,,"To date, multiple serotypes and genotypes of infectious bronchitis virus (IBV) have been isolated and identified. In order to provide more information on the viral evolution of IBVs, a new virulent strain named GX-NN09032, isolated from Guangxi, China, in 2009, was sequenced, and phylogenetic and recombination analyses were conducted. Furthermore, potential recombination events associated with GX-NN09032 were found in four IBV strains, including GX-YL5, DY07, CK/CH/SD09/005, TC07-2. The present study suggested that GX-NN09032 might contribute to the emergence of modern IBV variants through recombination.",,"['He, Kun', 'Li, Meng', 'Wei, Ping', 'Mo, Mei-lan', 'Wei, Tian-chao', 'Li, Kang-ran']",,,,
,PMC,Heparan Sulfate Facilitates Rift Valley Fever Virus Entry into the Cell,http://dx.doi.org/10.1128/JVI.01364-12,PMC3503077,,,"Rift Valley fever virus (RVFV), an emerging arthropod-borne pathogen, has a broad host and cell tropism. Here we report that the glycosaminoglycan heparan sulfate, abundantly present on the surface of most animal cells, is required for efficient entry of RVFV. Entry was significantly reduced by preincubating the virus inoculum with highly sulfated heparin, by enzymatic removal of heparan sulfate from cells and in cells genetically deficient in heparan sulfate synthesis.",,"['de Boer, S. M.', 'Kortekaas, J.', 'de Haan, C. A. M.', 'Rottier, P. J. M.', 'Moormann, R. J. M.', 'Bosch, B. J.']",,,,
,PMC,A Novel Group of Avian Astroviruses in Wild Aquatic Birds,http://dx.doi.org/10.1128/JVI.02105-12,PMC3503074,,,"Using a pan-astrovirus reverse transcription-PCR assay, a great diversity of novel avastroviruses was detected from wild bird and poultry samples. Two groups of astroviruses detected from wild birds are genetically related or highly similar to previously known viruses in poultry. Most interestingly, a novel group of astroviruses was detected in wild aquatic birds. Our results also reveal that different groups of astroviruses might have difference host ranges. This study has expanded our understanding regarding avastrovirus ecology.",,"['Chu, Daniel K. W.', 'Leung, Connie Y. H.', 'Perera, Harsha K. K.', 'Ng, Erica M.', 'Gilbert, Martin', 'Joyner, Priscilla H.', 'Grioni, Alessandro', 'Ades, Gary', 'Guan, Yi', 'Peiris, Joseph S. M.', 'Poon, Leo L. M.']",,,,
,PMC,Utilization of Sialylated Glycans as Coreceptors Enhances the Neurovirulence of Serotype 3 Reovirus,http://dx.doi.org/10.1128/JVI.01822-12,PMC3503066,,,"Mammalian reoviruses display serotype-specific patterns of tropism and disease in the murine central nervous system (CNS) attributable to polymorphisms in viral attachment protein σ1. While all reovirus serotypes use junctional adhesion molecule-A as a cellular receptor, they differ in their utilization of carbohydrate coreceptors. This observation raises the possibility that carbohydrate binding by σ1 influences reovirus pathology in the CNS. In this study, we sought to define the function of carbohydrate binding in reovirus neuropathogenesis. Newborn mice were inoculated intramuscularly with wild-type strain type 3 Dearing (T3D) and T3D-σ1R202W, a point mutant T3D derivative that does not bind sialic acid (SA). Infected mice were monitored for survival, and viral loads at the sites of primary and secondary replication were quantified. Fewer mice inoculated with the wild-type virus survived in comparison to those inoculated with the mutant virus. The wild-type virus also produced higher titers in the spinal cord and brain at late times postinoculation but lower titers in the liver in comparison to those produced by the mutant virus. In addition, the wild-type virus was more virulent and produced higher titers in the brain than the mutant following intracranial inoculation. These animal infectivity studies suggest that T3D-σ1R202W harbors a defect in neural growth. Concordantly, compared with the wild-type virus, the mutant virus displayed a decreased capacity to infect and replicate in primary cultures of cortical neurons, a property dependent on cell surface SA. These results suggest that SA binding enhances the kinetics of reovirus replication in neural tissues and highlight a functional role for sialylated glycans as reovirus coreceptors in the CNS.",,"['Frierson, Johnna M.', 'Pruijssers, Andrea J.', 'Konopka, Jennifer L.', 'Reiter, Dirk M.', 'Abel, Ty W.', 'Stehle, Thilo', 'Dermody, Terence S.']",,,,
,PMC,"Japanese Encephalitis Virus Enters Rat Neuroblastoma Cells via a pH-Dependent, Dynamin and Caveola-Mediated Endocytosis Pathway",http://dx.doi.org/10.1128/JVI.00903-12,PMC3503063,,,"Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus and one of the most common agents of viral encephalitis. The infectious entry process of JEV into host cells remains largely unknown. Here, we present a systemic study concerning the cellular entry mechanism of JEV to B104 rat neuroblastoma cells. It was observed that JEV internalization was inhibited by chloroquine and ammonium chloride, both of which can elevate the pH of acidic organelles. However, JEV entry was not affected by chlorpromazine, overexpression of a dominant-negative form of EPS 15 protein, or silencing of the clathrin heavy chain by small interfering RNA (siRNA). These results suggested that JEV entry depended on the acidic intracellular pH but was independent of clathrin. We found that endocytosis of JEV was dependent on membrane cholesterol and was inhibited by inactivation of caveolin-1 with siRNA or dominant-negative mutants. It was also shown, by using the inhibitor dynasore, the K44A mutant, and specific siRNA, that dynamin was required for JEV entry. Phagocytosis or macropinocytosis did not play a role in JEV internalization. In addition, we showed that JEV entry into the neuroblastoma cells is not virus strain specific by assessing the effect of the pharmacological inhibitors on the internalization of JEV belonging to different genotypes. Taken together, our results demonstrate that JEV enters B104 cells through a dynamin-dependent caveola-mediated uptake with a pH-dependent step, which is distinct from the clathrin-mediated endocytosis used by most flaviviruses.",,"['Zhu, Yong-Zhe', 'Xu, Qing-Qiang', 'Wu, Da-Ge', 'Ren, Hao', 'Zhao, Ping', 'Lao, Wen-Guang', 'Wang, Yan', 'Tao, Qing-Yuan', 'Qian, Xi-Jing', 'Wei, You-Heng', 'Cao, Ming-Mei', 'Qi, Zhong-Tian']",,,,
,PMC,Complete Genome Sequence of a Virulent Porcine Epidemic Diarrhea Virus Strain,http://dx.doi.org/10.1128/JVI.02635-12,PMC3503061,,,"In recent years, acute outbreaks of epizootic diarrhea have occurred on many swine farms in China. Although the putative causative virus of the disease was not isolated, the genomic sequence of porcine epidemic diarrhea virus (PEDV) was consistently detected from feces of diseased pigs by reverse transcription-PCR (RT-PCR). Here we report a complete genome sequence of PEDV which is apparently different from those of early PEDV circulated in Chinese swine herds.",,"['Zhou, Yan-jun', 'Wu, Yu-lu', 'Zhu, Jian-ping', 'Tong, Wu', 'Yu, Hai', 'Jiang, Yi-feng', 'Tong, Guang-zhi']",,,,
,PMC,Induction of Alternatively Activated Macrophages Enhances Pathogenesis during Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/JVI.01689-12,PMC3503056,,,"Infection with severe acute respiratory syndrome coronavirus (SARS-CoV) causes acute lung injury (ALI) that often leads to severe lung disease. A mouse model of acute SARS-CoV infection has been helpful in understanding the host response to infection; however, there are still unanswered questions concerning SARS-CoV pathogenesis. We have shown that STAT1 plays an important role in the severity of SARS-CoV pathogenesis and that it is independent of the role of STAT1 in interferon signaling. Mice lacking STAT1 have greater weight loss, severe lung pathology with pre-pulmonary-fibrosis-like lesions, and an altered immune response following infection with SARS-CoV. We hypothesized that STAT1 plays a role in the polarization of the immune response, specifically in macrophages, resulting in a worsened outcome. To test this, we created bone marrow chimeras and cell-type-specific knockouts of STAT1 to identify which cell type(s) is critical to protection from severe lung disease after SARS-CoV infection. Bone marrow chimera experiments demonstrated that hematopoietic cells are responsible for the pathogenesis in STAT1(−/−) mice, and because of an induction of alternatively activated (AA) macrophages after infection, we hypothesized that the AA macrophages were critical for disease severity. Mice with STAT1 in either monocytes and macrophages (LysM/STAT1) or ciliated lung epithelial cells (FoxJ1/STAT1) deleted were created. Following infection, LysM/STAT1 mice display severe lung pathology, while FoxJ1/STAT1 mice display normal lung pathology. We hypothesized that AA macrophages were responsible for this STAT1-dependent pathology and therefore created STAT1/STAT6(−/−) double-knockout mice. STAT6 is essential for the development of AA macrophages. Infection of the double-knockout mice displayed a lack of lung disease and prefibrotic lesions, suggesting that AA macrophage production may be the cause of STAT1-dependent lung disease. We propose that the control of AA macrophages by STAT1 is critical to regulating immune pathologies and for protection from long-term progression to fibrotic lung disease in a mouse model of SARS-CoV infection.",,"['Page, Carly', 'Goicochea, Lindsay', 'Matthews, Krystal', 'Zhang, Yong', 'Klover, Peter', 'Holtzman, Michael J.', 'Hennighausen, Lothar', 'Frieman, Matthew']",,,,
,PMC,Complete Genome Sequence of Novel Porcine Epidemic Diarrhea Virus Strain GD-1 in China,http://dx.doi.org/10.1128/JVI.02615-12,PMC3503055,,,"Porcine epidemic diarrhea virus (PEDV) infection, which causes acute diarrhea and dehydration in suckling piglets, has become a serious problem for the swine industry of China in recent years. In this study, a virulent PEDV strain, GD-1, was obtained from fecal samples from suckling piglets that suffered from severe diarrhea in 2011 in Guangdong, China. Here we describe the complete genome sequence of strain GD-1, which may be helpful in further understanding the molecular epidemiology and genetic diversity of PEDV field isolates in China.",,"['Wei, Zhong-yan', 'Lu, Wen-hui', 'Li, Zhi-li', 'Mo, Jian-yue', 'Zeng, Xi-duo', 'Zeng, Zhi-liang', 'Sun, Bao-li', 'Chen, Feng', 'Xie, Qing-Mei', 'Bee, Ying-zuo', 'Ma, Jing-yun']",,,,
,PMC,Genetic Characterization of Simian Foamy Viruses Infecting Humans,http://dx.doi.org/10.1128/JVI.01715-12,PMC3503051,,,"Simian foamy viruses (SFVs) are retroviruses that are widespread among nonhuman primates (NHPs). SFVs actively replicate in their oral cavity and can be transmitted to humans after NHP bites, giving rise to a persistent infection even decades after primary infection. Very few data on the genetic structure of such SFVs found in humans are available. In the framework of ongoing studies searching for SFV-infected humans in south Cameroon rainforest villages, we studied 38 SFV-infected hunters whose times of infection had presumably been determined. By long-term cocultures of peripheral blood mononuclear cells with BHK-21 cells, we isolated five new SFV strains and obtained complete genomes of SFV strains from chimpanzee (Pan troglodytes troglodytes; strains BAD327 and AG15), monkey (Cercopithecus nictitans; strain AG16), and gorilla (Gorilla gorilla; strains BAK74 and BAD468). These zoonotic strains share a very high degree of similarity with their NHP counterparts and have a high degree of conservation of the genetic elements important for viral replication. Interestingly, analysis of FV DNA sequences obtained before cultivation revealed variants with deletions in both the U3 region and tas that may correlate with in vivo chronicity in humans. Genomic changes in bet (a premature stop codon) and gag were also observed. To determine if such changes were specific to zoonotic strains, we studied local SFV-infected chimpanzees and found the same genomic changes. Our study reveals that natural polymorphism of SFV strains does exist at both the intersubspecies level (gag, bet) and the intrasubspecies (U3, tas) levels but does not seem to reflect a viral adaptation specific to zoonotic SFV strains.",,"['Rua, Réjane', 'Betsem, Edouard', 'Calattini, Sara', 'Saib, Ali', 'Gessain, Antoine']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Protein nsp1 Is a Novel Eukaryotic Translation Inhibitor That Represses Multiple Steps of Translation Initiation,http://dx.doi.org/10.1128/JVI.01958-12,PMC3503042,,,"Severe acute respiratory syndrome (SARS) coronavirus nonstructural protein 1 (nsp1) binds to the 40S ribosomal subunit and inhibits translation, and it also induces a template-dependent endonucleolytic cleavage of host mRNAs. nsp1 inhibits the translation of cap-dependent and internal ribosome entry site (IRES)-driven mRNAs, including SARS coronavirus mRNAs, hepatitis C virus (HCV), and cricket paralysis virus (CrPV) IRES-driven mRNAs that are resistant to nsp1-induced RNA cleavage. We used an nsp1 mutant, nsp1-CD, lacking the RNA cleavage function, to delineate the mechanism of nsp1-mediated translation inhibition and identify the translation step(s) targeted by nsp1. nsp1 and nsp1-CD had identical inhibitory effects on mRNA templates that are resistant to nsp1-induced RNA cleavage, implying the validity of using nsp1-CD to dissect the translation inhibition function of nsp1. We provide evidence for a novel mode of action of nsp1. nsp1 inhibited the translation initiation step by targeting at least two separate stages: 48S initiation complex formation and the steps involved in the formation of the 80S initiation complex from the 48S complex. nsp1 had a differential, mRNA template-dependent, inhibitory effect on 48S and 80S initiation complex formation. nsp1 inhibited different steps of translation initiation on CrPV and HCV IRES, both of which initiate translation via an IRES-40S binary complex intermediate; nsp1 inhibited binary complex formation on CrPV IRES and 48S complex formation on HCV IRES. Collectively, the data revealed that nsp1 inhibited translation by exerting its effect on multiple stages of translation initiation, depending on the mechanism of initiation operating on the mRNA template.",,"['Lokugamage, Kumari G.', 'Narayanan, Krishna', 'Huang, Cheng', 'Makino, Shinji']",,,,
,PMC,Differential Pathological and Immune Responses in Newly Weaned Ferrets Are Associated with a Mild Clinical Outcome of Pandemic 2009 H1N1 Infection,http://dx.doi.org/10.1128/JVI.01456-12,PMC3503035,,,"Young children are typically considered a high-risk group for disease associated with influenza virus infection. Interestingly, recent clinical reports suggested that young children were the smallest group of cases with severe pandemic 2009 H1N1 (H1N1pdm) influenza virus infection. Here we established a newly weaned ferret model for the investigation of H1N1pdm infection in young age groups compared to adults. We found that young ferrets had a significantly milder fever and less weight loss than adult ferrets, which paralleled the mild clinical symptoms in the younger humans. Although there was no significant difference in viral clearance, disease severity was associated with pulmonary pathology, where newly weaned ferrets had an earlier pathology improvement. We examined the immune responses associated with protection of the young age group during H1N1pdm infection. We found that interferon and regulatory interleukin-10 responses were more robust in the lungs of young ferrets. In contrast, myeloperoxidase and major histocompatibility complex responses were persistently higher in the adult lungs; as well, the numbers of inflammation-prone granulocytes were highly elevated in the adult peripheral blood. Importantly, we observed that H1N1pdm infection triggered formation of lung structures that resembled inducible bronchus-associated lymphoid tissues (iBALTs) in young ferrets which were associated with high levels of homeostatic chemokines CCL19 and CXCL13, but these were not seen in the adult ferrets with severe disease. These results may be extrapolated to a model of the mild disease seen in human children. Furthermore, these mechanistic analyses provide significant new insight into the developing immune system and effective strategies for intervention and vaccination against respiratory viruses.",,"['Huang, Stephen S. H.', 'Banner, David', 'Degousee, Norbert', 'Leon, Alberto J.', 'Xu, Louling', 'Paquette, Stephane G.', 'Kanagasabai, Thirumagal', 'Fang, Yuan', 'Rubino, Salvatore', 'Rubin, Barry', 'Kelvin, David J.', 'Kelvin, Alyson A.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.02412-12,PMC3503028,,,,,,,,,
,PMC,Global Secretome Characterization of Herpes Simplex Virus 1-Infected Human Primary Macrophages,http://dx.doi.org/10.1128/JVI.01545-12,PMC3497699,,,"Herpes simplex virus 1 (HSV-1) is a common pathogen infecting the majority of people worldwide at some stage in their lives. The early host response to viral infection is initiated by the cells of the innate immune response, including macrophages. Here, we have characterized the secretome of HSV-1-infected human primary macrophages using high-throughput quantitative proteomics. We identified and quantified 516 distinct human proteins with high confidence from the macrophage secretome upon HSV-1 infection, and the secretion of 411 proteins was >2-fold increased upon beta interferon (IFN-β) priming and/or HSV-1 infection. Bioinformatics analysis of the secretome data revealed that most of the secreted proteins were intracellular, and almost 80% of the proteins whose secretion increased more than 2-fold were known exosomal proteins. This strongly suggests that nonclassical, vesicle-mediated protein secretion is activated in IFN-β-primed and HSV-1-infected macrophages. Proteins related to immune and inflammatory responses, interferon-induced proteins, and endogenous danger signal proteins were efficiently secreted upon IFN-β priming and HSV-1 infection. The secreted IFN-induced proteins include interferon-induced tetratricopeptide protein 2 (IFIT2), IFIT3, signal transducer and activator of transcription 1 (STAT1), and myxovirus resistance protein A (MxA), implicating that these proteins also have important extracellular antiviral functions. Proinflammatory cytokine interleukin-1β was not released by HSV-1-infected macrophages, demonstrating that HSV-1 can antagonize inflammasome function. In conclusion, our results provide a global view of the secretome of HSV-1-infected macrophages, revealing host factors possibly having a role in antiviral defense.",,"['Miettinen, Juho J.', 'Matikainen, Sampsa', 'Nyman, Tuula A.']",,,,
,PMC,Neutralizing Capacity of Monoclonal Antibodies That Recognize Peptide Sequences Underlying the Carbohydrates on gp41 of Simian Immunodeficiency Virus,http://dx.doi.org/10.1128/JVI.01959-12,PMC3497684,,,"Extensive glycosylation of the envelope spikes of human and simian immunodeficiency virus (HIV and SIV) is an important factor for the resistance of these viruses to neutralization by antibodies. SIVmac239 gp41 has three closely spaced sites for N-linked carbohydrate attachment. Rhesus macaques experimentally infected with mutant versions of SIVmac239 lacking two or three of these carbohydrate sites developed strong serum reactivity against mutated peptide sequences at the site of these glycosylations, as well as high titers of neutralizing activity to the mutant viruses (E. Yuste et al., J. Virol. 82:12472–12486, 2008). However, whether antibodies that recognize these underlying peptides have neutralizing activity has not been directly demonstrated. Here we describe the isolation and characterization of three gp41-specific monoclonal antibodies (4G8, 6G8, and 7D6) from one of these mutant-infected monkeys. All three antibodies reacted with mutant gp41 from viral particles and also with peptides corresponding to mutated sequences. Slight differences in peptide specificities were observed among the three antibodies. Sequence analysis revealed that the heavy chains of all three antibodies were derived from the same germ line heavy-chain segment (IGHV4-59*01), but they all had very different sequences in complementarity-determining region 3. The light chains of all three antibodies were very closely related to one another. All three antibodies had neutralizing activity to mutant viruses deficient in gp41 carbohydrate attachment, but they did not neutralize the parental SIVmac239. These results demonstrate unambiguously that antibodies with specificity for peptide sequences underlying gp41 carbohydrates can effectively neutralize SIV when these carbohydrates are absent. However, the presence of these gp41 carbohydrates effectively shields the virus from antibodies that would otherwise neutralize viral infectivity.",,"['Martinez-Navio, José M.', 'Desrosiers, Ronald C.']",,,,
,PMC,Evidence Supporting a Zoonotic Origin of Human Coronavirus Strain NL63,http://dx.doi.org/10.1128/JVI.00906-12,PMC3497669,,,"The relationship between bats and coronaviruses (CoVs) has received considerable attention since the severe acute respiratory syndrome (SARS)-like CoV was identified in the Chinese horseshoe bat (Rhinolophidae) in 2005. Since then, several bats throughout the world have been shown to shed CoV sequences, and presumably CoVs, in the feces; however, no bat CoVs have been isolated from nature. Moreover, there are very few bat cell lines or reagents available for investigating CoV replication in bat cells or for isolating bat CoVs adapted to specific bat species. Here, we show by molecular clock analysis that alphacoronavirus (α-CoV) sequences derived from the North American tricolored bat (Perimyotis subflavus) are predicted to share common ancestry with human CoV (HCoV)-NL63, with the most recent common ancestor between these viruses occurring approximately 563 to 822 years ago. Further, we developed immortalized bat cell lines from the lungs of this bat species to determine if these cells were capable of supporting infection with HCoVs. While SARS-CoV, mouse-adapted SARS-CoV (MA15), and chimeric SARS-CoVs bearing the spike genes of early human strains replicated inefficiently, HCoV-NL63 replicated for multiple passages in the immortalized lung cells from this bat species. These observations support the hypothesis that human CoVs are capable of establishing zoonotic-reverse zoonotic transmission cycles that may allow some CoVs to readily circulate and exchange genetic material between strains found in bats and other mammals, including humans.",,"['Huynh, Jeremy', 'Li, Shimena', 'Yount, Boyd', 'Smith, Alexander', 'Sturges, Leslie', 'Olsen, John C.', 'Nagel, Juliet', 'Johnson, Joshua B.', 'Agnihothram, Sudhakar', 'Gates, J. Edward', 'Frieman, Matthew B.', 'Baric, Ralph S.', 'Donaldson, Eric F.']",,,,
,PMC,Essential Cell-Autonomous Role for Interferon (IFN) Regulatory Factor 1 in IFN-γ-Mediated Inhibition of Norovirus Replication in Macrophages,http://dx.doi.org/10.1128/JVI.01564-12,PMC3497668,,,"Noroviruses (NVs) cause the majority of cases of epidemic nonbacterial gastroenteritis worldwide and contribute to endemic enteric disease. However, the molecular mechanisms responsible for immune control of their replication are not completely understood. Here we report that the transcription factor interferon regulatory factor 1 (IRF-1) is required for control of murine NV (MNV) replication and pathogenesis in vivo. This led us to studies documenting a cell-autonomous role for IRF-1 in gamma interferon (IFN-γ)-mediated inhibition of MNV replication in primary macrophages. This role of IRF-1 in the inhibition of MNV replication by IFN-γ is independent of IFN-αβ signaling. While the signal transducer and activator of transcription STAT-1 was also required for IFN-γ-mediated inhibition of MNV replication in vitro, class II transactivator (CIITA), interferon regulatory factor 3 (IRF-3), and interferon regulatory factor 7 (IRF-7) were not required. We therefore hypothesized that there must be a subset of IFN-stimulated genes (ISGs) regulated by IFN-γ in a manner dependent only on STAT-1 and IRF-1. Analysis of transcriptional profiles of macrophages lacking various transcription factors confirmed this hypothesis. These studies identify a key role for IRF-1 in IFN-γ-dependent control of norovirus infection in mice and macrophages.",,"['Maloney, Nicole S.', 'Thackray, Larissa B.', 'Goel, Gautam', 'Hwang, Seungmin', 'Duan, Erning', 'Vachharajani, Punit', 'Xavier, Ramnik', 'Virgin, Herbert W.']",,,,
,PMC,Longitudinal Analysis of the Human Antibody Response to Chikungunya Virus Infection: Implications for Serodiagnosis and Vaccine Development,http://dx.doi.org/10.1128/JVI.01780-12,PMC3497641,,,"Chikungunya virus (CHIKV) is an alphavirus which causes chronic and incapacitating arthralgia in humans. Although previous studies have shown that antibodies against the virus are produced during and after infection, the fine specificity of the antibody response against CHIKV is not known. Here, using plasma from patients at different times postinfection, we characterized the antibody response against various proteins of the virus. We have shown that the E2 and E3 glycoproteins and the capsid and nsP3 proteins are targets of the anti-CHIKV antibody response. Moreover, we have identified the different regions in these proteins which contain the linear epitopes recognized by the anti-CHIKV antibodies and determined their structural localization. Data also illustrated the effect of a single K(252)Q amino acid change at the E2 glycoprotein that was able to influence antibody binding and interaction between the antibodies and epitope because of the changes of epitope-antibody binding capacity. This study provides important knowledge that will not only aid in the understanding of the immune response to CHIKV infection but also provide new knowledge in the design of modern vaccine development. Furthermore, these pathogen-specific epitopes could be used for future seroepidemiological studies that will unravel the molecular mechanisms of human immunity and protection from CHIKV disease.",,"['Kam, Yiu-Wing', 'Lee, Wendy W. L.', 'Simarmata, Diane', 'Harjanto, Sumitro', 'Teng, Terk-Shin', 'Tolou, Hugues', 'Chow, Angela', 'Lin, Raymond T. P.', 'Leo, Yee-Sin', 'Rénia, Laurent', 'Ng, Lisa F. P.']",,,,
,PMC,Foot-and-Mouth Disease Virus Induces Autophagosomes during Cell Entry via a Class III Phosphatidylinositol 3-Kinase-Independent Pathway,http://dx.doi.org/10.1128/JVI.00846-12,PMC3497631,,,"Autophagy is an intracellular pathway that can contribute to innate antiviral immunity by delivering viruses to lysosomes for degradation or can be beneficial for viruses by providing specialized membranes for virus replication. Here, we show that the picornavirus foot-and-mouth disease virus (FMDV) induces the formation of autophagosomes. Induction was dependent on Atg5, involved processing of LC3 to LC3II, and led to a redistribution of LC3 from the cytosol to punctate vesicles indicative of authentic autophagosomes. Furthermore, FMDV yields were reduced in cells lacking Atg5, suggesting that autophagy may facilitate FMDV infection. However, induction of autophagosomes by FMDV appeared to differ from starvation, as the generation of LC3 punctae was not inhibited by wortmannin, implying that FMDV-induced autophagosome formation does not require the class III phosphatidylinositol 3-kinase (PI3-kinase) activity of vps34. Unlike other picornaviruses, for which there is strong evidence that autophagosome formation is linked to expression of viral nonstructural proteins, FMDV induced autophagosomes very early during infection. Furthermore, autophagosomes could be triggered by either UV-inactivated virus or empty FMDV capsids, suggesting that autophagosome formation was activated during cell entry. Unlike other picornaviruses, FMDV-induced autophagosomes did not colocalize with the viral 3A or 3D protein. In contrast, ∼50% of the autophagosomes induced by FMDV colocalized with VP1. LC3 and VP1 also colocalized with the cellular adaptor protein p62, which normally targets ubiquitinated proteins to autophagosomes. These results suggest that FMDV induces autophagosomes during cell entry to facilitate infection, but not to provide membranes for replication.",,"['Berryman, Stephen', 'Brooks, Elizabeth', 'Burman, Alison', 'Hawes, Philippa', 'Roberts, Rebecca', 'Netherton, Christopher', 'Monaghan, Paul', 'Whelband, Matthew', 'Cottam, Eleanor', 'Elazar, Zvulun', 'Jackson, Terry', 'Wileman, Thomas']",,,,
,PMC,Rift Valley Fever Virus Strain MP-12 Enters Mammalian Host Cells via Caveola-Mediated Endocytosis,http://dx.doi.org/10.1128/JVI.02242-12,PMC3497621,,,"Rift Valley fever virus (RVFV) is a zoonotic pathogen capable of causing serious morbidity and mortality in both humans and livestock. The lack of efficient countermeasure strategies, the potential for dispersion into new regions, and the pathogenesis in humans and livestock make RVFV a serious public health concern. The receptors, cellular factors, and entry pathways used by RVFV and other members of the family Bunyaviridae remain largely uncharacterized. Here we provide evidence that RVFV strain MP-12 uses dynamin-dependent caveola-mediated endocytosis for cell entry. Caveolae are lipid raft domains composed of caveolin (the main structural component), cholesterol, and sphingolipids. Caveola-mediated endocytosis is responsible for the uptake of a wide variety of host ligands, as well as bacteria, bacterial toxins, and a number of viruses. To determine the cellular entry mechanism of RVFV, we used small-molecule inhibitors, RNA interference (RNAi), and dominant negative (DN) protein expression to inhibit the major mammalian cell endocytic pathways. Inhibitors and RNAi specific for macropinocytosis and clathrin-mediated endocytosis had no effect on RVFV infection. In contrast, inhibitors of caveola-mediated endocytosis, and RNAi targeted to caveolin-1 and dynamin, drastically reduced RVFV infection in multiple cell lines. Expression of DN caveolin-1 also reduced RVFV infection significantly, while expression of DN EPS15, a protein required for the assembly of clathrin-coated pits, and DN PAK-1, an obligate mediator of macropinocytosis, had no significant impact on RVFV infection. These results together suggest that the primary mechanism of RVFV MP-12 uptake is dynamin-dependent, caveolin-1-mediated endocytosis.",,"['Harmon, Brooke', 'Schudel, Benjamin R.', 'Maar, Dianna', 'Kozina, Carol', 'Ikegami, Tetsuro', 'Tseng, Chien-Te Kent', 'Negrete, Oscar A.']",,,,
,PMC,Hepatitis C Virus Activates Bcl-2 and MMP-2 Expression through Multiple Cellular Signaling Pathways,http://dx.doi.org/10.1128/JVI.01136-12,PMC3497616,,,"Hepatitis C virus (HCV) infection is associated with numerous liver diseases and causes serious global health problems, but the mechanisms underlying the pathogenesis of HCV infections remain largely unknown. In this study, we demonstrate that signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase-2 (MMP-2), and B-cell lymphoma 2 (Bcl-2) are significantly stimulated in HCV-infected patients. We further show that HCV activates STAT3, MMP-2, Bcl-2, extracellular regulated protein kinase (ERK), and c-Jun N-terminal kinase (JNK) in infected Huh7.5.1 cells. Functional screening of HCV proteins revealed that nonstructural protein 4B (NS4B) is responsible for the activation of MMP-2 and Bcl-2 by stimulating STAT3 through repression of the suppressor of cytokine signaling 3 (SOCS3). Our results also demonstrate that multiple signaling cascades, including several members of the protein kinase C (PKC) family, JNK, ERK, and STAT3, play critical roles in the activation of MMP-2 and Bcl-2 mediated by NS4B. Further studies revealed that the C-terminal domain (CTD) of NS4B is sufficient for the activation of STAT3, JNK, ERK, MMP-2, and Bcl-2. We also show that amino acids 227 to 250 of NS4B are essential for regulation of STAT3, JNK, ERK, MMP-2, and Bcl-2, and among them, three residues (237L, 239S, and 245L) are crucial for this regulation. Thus, we reveal a novel mechanism underlying HCV pathogenesis in which multiple intracellular signaling cascades are cooperatively involved in the activation of two important cellular factors, MMP-2 and Bcl-2, in response to HCV infection.",,"['Li, Youxing', 'Zhang, Qi', 'Liu, Yin', 'Luo, Zhen', 'Kang, Lei', 'Qu, Jing', 'Liu, Weiyong', 'Xia, Xueshan', 'Liu, Yingle', 'Wu, Kailang', 'Wu, Jianguo']",,,,
,PMC,"Drivers, dynamics, and control of emerging vector-borne zoonotic diseases",http://dx.doi.org/10.1016/S0140-6736(12)61151-9,PMC3739480,,,"Emerging vector-borne diseases represent an important issue for global health. Many vector-borne pathogens have appeared in new regions in the past two decades, and many endemic diseases have increased in incidence. Although introductions and local emergence are frequently considered distinct processes, many emerging endemic pathogens are in fact invading at a local scale coincident with habitat change. We highlight key differences in the dynamics and disease burden that result from increased pathogen transmission following habitat change compared with the introduction of pathogens to new regions. Truly in situ emergence is commonly driven by changes in human factors as much as by enhanced enzootic cycles whereas pathogen invasion results from anthropogenic trade and travel and suitable conditions for a pathogen, including hosts, vectors, and climate. Once established, ecological factors related to vector characteristics shape the evolutionary selective pressure on pathogens that may result in increased use of humans as transmission hosts. We describe challenges inherent in the control of vector-borne zoonotic diseases and some emerging non-traditional strategies that may be more effective in the long term.",,"['Kilpatrick, A. Marm', 'Randolph, Sarah E.']",,,,
,PMC,Prediction and prevention of the next pandemic zoonosis,http://dx.doi.org/10.1016/S0140-6736(12)61684-5,PMC3712877,,,"Most pandemics—eg, HIV/AIDS, severe acute respiratory syndrome, pandemic influenza—originate in animals, are caused by viruses, and are driven to emerge by ecological, behavioural, or socioeconomic changes. Despite their substantial effects on global public health and growing understanding of the process by which they emerge, no pandemic has been predicted before infecting human beings. We review what is known about the pathogens that emerge, the hosts that they originate in, and the factors that drive their emergence. We discuss challenges to their control and new efforts to predict pandemics, target surveillance to the most crucial interfaces, and identify prevention strategies. New mathematical modelling, diagnostic, communications, and informatics technologies can identify and report hitherto unknown microbes in other species, and thus new risk assessment approaches are needed to identify microbes most likely to cause human disease. We lay out a series of research and surveillance opportunities and goals that could help to overcome these challenges and move the global pandemic strategy from response to pre-emption.",,"['Morse, Stephen S', 'Mazet, Jonna A K', 'Woolhouse, Mark', 'Parrish, Colin R', 'Carroll, Dennis', 'Karesh, William B', 'Zambrana-Torrelio, Carlos', 'Lipkin, W Ian', 'Daszak, Peter']",,,,
,PMC,Anatomy of a pandemic,http://dx.doi.org/10.1016/S0140-6736(12)61887-X,PMC3712832,,,,,"Daszak, Peter",,,,
,PMC,Detecting Respiratory Viruses in Asymptomatic Children,http://dx.doi.org/10.1097/INF.0b013e318265a804,PMC3505556,,,"BACKGROUND: Viral respiratory infections are among the most common reasons for hospitalization of children in the United States. Our objective was to compare molecular and conventional methods in a cohort of hospitalized children with and without symptoms of respiratory viral illness (RVI). METHODS: Retrospective cohort study of infants and toddlers hospitalized between December 2007 and March 2008 at Johns Hopkins Hospital. 569 of 641 patient visits (89%) were tested on admission. Conventional tests (immunochromatography, direct fluorescent antibody, shell vial, and tube culture) were performed on all patients and nucleic acid tests (NATs) were performed on available samples (n=306). Viruses were grouped into those routinely (Group 1) and those not routinely (Group 2) detected by conventional methods. RESULTS: In children with RVI symptoms (N=148), NATs identified a virus in 83% specimens compared with 49% by conventional methods (p<0.001), but detected a similar percentage of specimens with Group 1 viruses (48.6% and 55.4%, p=0.13) compared with conventional tests. In children without RVI symptoms (N=158), NATs identified a virus in 41.7% specimens compared with 4.4% by conventional tests (p<0.001) and identified more Group 1 viruses (9.5% and 4.4%, p=0.03) compared with conventional tests. Group 2 viruses were identified by NATs in a similar percentage of symptomatic and asymptomatic patients (25% and 32.3%, p=0.20). CONCLUSION: Molecular assays may have several advantages over conventional methods for detecting respiratory viruses, including improved sensitivity and rapid detection, but given the high prevalence of positive results in children without RVI symptoms, results should be interpreted cautiously.",,"['Advani, Sonali', 'Sengupta, Arnab', 'Forman, Michael', 'Valsamakis, Alexandra', 'Milstone, Aaron']",,,,
,PMC,A Pilot Study Comparing the Development of EIAV Env-Specific Antibodies Induced by DNA/Recombinant Vaccinia-Vectored Vaccines and an Attenuated Chinese EIAV Vaccine,http://dx.doi.org/10.1089/vim.2012.0014,PMC3518545,,,"Data from successful attenuated lentiviral vaccine studies indicate that fully mature Env-specific antibodies characterized by high titer, high avidity, and the predominant recognition of conformational epitopes are associated with protective efficacy. Although vaccination with a DNA prime/recombinant vaccinia-vectored vaccine boost strategy has been found to be effective in some trials with non-human primate/simian/human immunodeficiency virus (SHIV) models, it remains unclear whether this vaccination strategy could elicit mature equine infectious anemia virus (EIAV) Env-specific antibodies, thus protecting vaccinated horses against EIAV infection. Therefore, in this pilot study we vaccinated horses using a strategy based on DNA prime/recombinant Tiantan vaccinia (rTTV)-vectored vaccines encoding EIAV env and gag genes, and observed the development of Env-specific antibodies, neutralizing antibodies, and p26-specific antibodies. Vaccination with DNA induced low titer, low avidity, and the predominant recognition of linear epitopes by Env-specific antibodies, which was enhanced by boosting vaccinations with rTTV vaccines. However, the maturation levels of Env-specific antibodies induced by the DNA/rTTV vaccines were significantly lower than those induced by the attenuated vaccine EIAV(FDDV). Additionally, DNA/rTTV vaccines did not elicit broadly neutralizing antibodies. After challenge with a virulent EIAV strain, all of the vaccinees and control horses died from EIAV disease. These data indicate that the regimen of DNA prime/rTTV vaccine boost did not induce mature Env-specific antibodies, which might have contributed to immune protection failure.",,"['Meng, Qinglai', 'Lin, Yuezhi', 'Ma, Jian', 'Ma, Yan', 'Zhao, Liping', 'Li, Shenwei', 'Yang, Kai', 'Zhou, Jianhua', 'Shen, Rongxian', 'Zhang, Xiaoyan', 'Shao, Yiming']",,,,
,PMC,Interferon-λs: Special Immunomodulatory Agents and Potential Therapeutic Targets,http://dx.doi.org/10.1159/000345365,PMC6741515,,,"Interferon (IFN)-λs are a new addition to the old IFN family and share many similarities, such as antiviral and antiproliferative characteristics, with type I IFNs. IFN-λs also exhibit unique characteristics in immunomodulation. Accumulating studies have indicated the interactions between IFN-λs and immune cells, which lead to the regulation of the latter. IFN-λs can influence dendritic cells (DCs) and their product, IFN-λs-DCs, can then regulate the function of T cells. On the other hand, IFN-λs can also directly affect T cells through inhibition of the T helper 2 cell (Th2) responses. IFN-λs have varying immunomodulatory functions under different physiological conditions or in different organs and can inhibit tumor growth via regulation of the immune system. Diseases associated with IFN-λs include asthma, allergy, and systemic lupus erythematosus. In this review, we summarize the current knowledge of the biology of IFN-λs and their immunomodulatory function in relevant human diseases.",,"['Zheng, Ya-wen', 'Li, Hui', 'Yu, Jin-pu', 'Zhao, Hua', 'Wang, Shizhen Emily', 'Ren, Xiu-bao']",,,,
,PMC,Potent Inhibition of Feline Coronaviruses with Peptidyl Compounds Targeting Coronavirus 3C-like Protease,http://dx.doi.org/10.1016/j.antiviral.2012.11.005,PMC3563934,,,"Feline coronavirus infection is common among domestic and exotic felid species and usually associated with mild or asymptomatic enteritis; however, feline infectious peritonitis (FIP) is a fatal disease of cats that is caused by systemic infection with a feline infectious peritonitis virus (FIPV), a variant of feline enteric coronavirus (FECV). Currently, there is no specific treatment approved for FIP despite the importance of FIP as the leading infectious cause of death in young cats. During the replication process, coronavirus produces viral polyproteins that are processed into mature proteins by viral proteases, the main protease (3C-like [3CL] protease) and the papain-like protease. Since the cleavages of viral polyproteins are an essential step for virus replication, blockage of viral protease is an attractive target for therapeutic intervention. Previously, we reported the generation of broad-spectrum peptidyl inhibitors against viruses that possess a 3C or 3CL protease. In this study, we further evaluated the antiviral effects of the peptidyl inhibitors against feline coronaviruses, and investigated the interaction between our protease inhibitor and a cathepsin B inhibitor, an entry blocker, against feline coronaviruses in cell culture. Herein we report that our compounds behave as reversible, competitive inhibitors of 3CL protease, potently inhibited the replication of feline coronaviruses (EC(50) in a nanomolar range) and, furthermore, the combination of cathepsin B and 3CL protease inhibitors led to a strong synergistic interaction against feline coronaviruses in cell culture systems.",,"['Kim, Yunjeong', 'Mandadapu, Sivakoteswara Rao', 'Groutas, William C.', 'Chang, Kyeong-Ok']",,,,
,PMC,Evolution of Bcl-2 homology (BH) motifs – homology versus homoplasy,http://dx.doi.org/10.1016/j.tcb.2012.10.010,PMC3582728,,,"Bcl-2 family proteins regulate apoptosis in animals. This protein family includes several homologous proteins and a collection of other proteins lacking sequence similarity except for a BH3 motif. Thus, membership in the Bcl-2 family requires only one of the four BH (Bcl-2 homology) motifs. On this basis, a growing number of diverse BH3-only proteins are being reported. While compelling cell biological and biophysical evidence validates many BH3-only proteins, claims about significant BH3 sequence similarity are often unfounded. Computational and phylogenetic analyses suggest that only some BH3 motifs arose by divergent evolution from a common ancestor (homology), while others arose by convergent evolution or random coincidence (homoplasy), challenging current assumptions about which proteins constitute the extended Bcl-2 family.",,"['Aouacheria, Abdel', 'de Laval, Valentine Rech', 'Combet, Christophe', 'Hardwick, J. Marie']",,,,
,PMC,Biological Characteristics and Propagation of Human Rhinovirus–C in Differentiated Sinus Epithelial Cells,http://dx.doi.org/10.1016/j.virol.2012.11.002,PMC3545098,,,"Information about the basic biological properties of Human rhinovirus C (HRV-C) viruses is lacking due to difficulties with culturing these viruses. Our objective was to develop a cell culture system to grow HRV-C. Epithelial cells from human sinuses (HSEC) were differentiated at air-liquid interface (ALI). Differentiated cultures supported 1-2 logs growth of HRV-C15 as detected by quantitative RT-PCR. Two distinguishing features of HRVs are acid lability and optimal growth at 33–34°C. We used this system to show that HRV-C15 is neutralized by low pH (4.5). In contrast to most HRV types, replication of HRV-C15 and HRV-C41 was similar at 34 and 37°C. The HSEC ALI provides a useful tool for quantitative studies of HRV-C replication. The ability of HRV-C to grow equally well at 34°C and 37°C may contribute to the propensity for HRV-C to cause lower airway illnesses in infants and children with asthma.",,"['Ashraf, Shamaila', 'Brockman-Schneider, Rebecca', 'Bochkov, Yury A.', 'Pasic, Thomas R.', 'Gern, James E.']",,,,
,PMC,Autophagy hijacked through viroporin-activated calcium/calmodulin-dependent kinase kinase-β signaling is required for rotavirus replication,http://dx.doi.org/10.1073/pnas.1216539109,PMC3528557,,,"Autophagy is a cellular degradation process involving an intracellular membrane trafficking pathway that recycles cellular components or eliminates intracellular microbes in lysosomes. Many pathogens subvert autophagy to enhance their replication, but the mechanisms these pathogens use to initiate the autophagy process have not been elucidated. This study identifies rotavirus as a pathogen that encodes a viroporin, nonstructural protein 4, which releases endoplasmic reticulum calcium into the cytoplasm, thereby activating a calcium/calmodulin-dependent kinase kinase-β and 5′ adenosine monophosphate-activated protein kinase-dependent signaling pathway to initiate autophagy. Rotavirus hijacks this membrane trafficking pathway to transport viral proteins from the endoplasmic reticulum to sites of viral replication to produce infectious virus. This process requires PI3K activity and autophagy-initiation proteins Atg3 and Atg5, and it is abrogated by chelating cytoplasmic calcium or inhibiting calcium/calmodulin-dependent kinase kinase-β. Although the early stages of autophagy are initiated, rotavirus infection also blocks autophagy maturation. These studies identify a unique mechanism of virus-mediated, calcium-activated signaling that initiates autophagy and hijacks this membrane trafficking pathway to transport viral proteins to sites of viral assembly.",,"['Crawford, Sue E.', 'Hyser, Joseph M.', 'Utama, Budi', 'Estes, Mary K.']",,,,
,PMC,Management of respiratory viral infections in hematopoietic cell transplant recipients,,PMC3512176,,,"Advances in stem cell transplantation procedures and the overall improvement in the clinical management of hematopoietic cell transplant (HCT) recipients over the past 2 decades have led to an increase in survival duration, in part owing to better strategies for prevention and treatment of post-transplant complications, including opportunistic infections. However, post-HCT infections remain a concern for HCT recipients, particularly infections caused by community respiratory viruses (CRVs), which can lead to significant morbidity and mortality. These viruses can potentially cause lower respiratory tract illness, which is associated with a higher mortality rate among HCT recipients. Clinical management of CRV infections in HCT recipients includes supportive care and antiviral therapy, especially in high-risk individuals, when available. Directed antiviral therapy is only available for influenza infections, where successful use of neuraminidase inhibitors (oseltamivir or zanamivir) and/or M2 inhibitors (amantadine or rimantadine) has been reported. Data on the successful use of ribavirin, with or without immunomodulators, for respiratory syncytial virus infections in HCT recipients has emerged over the past 2 decades but is still controversial at best because of a lack of randomized controlled trials. Because of the lack of directed antiviral therapy for most of these viruses, prevention should be emphasized for healthcare workers, patients, family, and friends and should include the promotion of the licensed inactivated influenza vaccine for HCT recipients, when indicated. In this review, we discuss the clinical management of respiratory viruses in this special patient population, focusing on commercially available antivirals, adjuvant therapy, and novel drugs under investigation, as well as on available means for prevention.",,"['Shah, Dimpy P', 'Ghantoji, Shashank S', 'Mulanovich, Victor E', 'Ariza-heredia, Ella J', 'Chemaly, Roy F']",,,,
,PMC,Sequential biogenesis of host cell membrane rearrangements induced by hepatitis C virus infection,http://dx.doi.org/10.1007/s00018-012-1213-0,PMC4901162,,,"Like most positive-strand RNA viruses, hepatitis C virus (HCV) forms a membrane-associated replication complex consisting of replicating RNA, viral and host proteins anchored to altered cell membranes. We used a combination of qualitative and quantitative electron microscopy (EM), immuno-EM and the 3D reconstruction of serial EM sections to analyze the host cell membrane alterations induced by HCV. Three different types of membrane alteration were observed : vesicles in clusters (ViCs), contiguous vesicles (CVs) and double-membrane vesicles (DMVs). The main ultrastructural change observed early in infection was the formation of a network of CVs surrounding the lipid droplets. Later stages in the infectious cycle were characterized by a large increase in the number of DMVs, which may be derived from the CVs. These DMVs are thought to constitute the membranous structures harboring the viral replication complexes in which viral replication is firmly and permanently established and to protect the virus against double-stranded RNA-triggered host antiviral responses.",,"['Ferraris, Pauline', 'Beaumont, Elodie', 'Uzbekov, Rustem', 'Brand, Denys', 'Gaillard, Julien', 'Blanchard, Emmanuelle', 'Roingeard, Philippe']",,,,
,PMC,"Slow, Reversible, Coupled Folding and Binding of the Spectrin Tetramerization Domain",http://dx.doi.org/10.1016/j.bpj.2012.10.012,PMC3512043,,,"Many intrinsically disordered proteins (IDPs) are significantly unstructured under physiological conditions. A number of these IDPs have been shown to undergo coupled folding and binding reactions whereby they can gain structure upon association with an appropriate partner protein. In general, these systems display weaker binding affinities than do systems with association between completely structured domains, with micromolar K(d) values appearing typical. One such system is the association between α- and β-spectrin, where two partially structured, incomplete domains associate to form a fully structured, three-helix bundle, the spectrin tetramerization domain. Here, we use this model system to demonstrate a method for fitting association and dissociation kinetic traces where, using typical biophysical concentrations, the association reactions are expected to be highly reversible. We elucidate the unusually slow, two-state kinetics of spectrin assembly in solution. The advantages of studying kinetics in this regime include the potential for gaining equilibrium constants as well as rate constants, and for performing experiments with low protein concentrations. We suggest that this approach would be particularly appropriate for high-throughput mutational analysis of two-state reversible binding processes.",,"['Shammas, S.L.', 'Rogers, J.M.', 'Hill, S.A.', 'Clarke, J.']",,,,
,PMC,Eponymy: Make that Hippocrates–Janin–Neumann–Reis–Bluthe– … –Behçet’s disease,http://dx.doi.org/10.1503/cmaj.109-4310,PMC3503899,,,,,"Collier, Roger",,,,
,PMC,Relationship between airborne detection of influenza A virus and the number of infected pigs,http://dx.doi.org/10.1016/j.tvjl.2012.09.024,PMC3582798,,,"Influenza A virus infects a wide range of species including both birds and mammals (including humans). One of the key routes by which the virus can infect populations of animals is by aerosol transmission. This study explored the relationship between number of infected pigs and the probability of detecting influenza virus RNA in bioaerosols through the course of an acute infection. Bioaerosols were collected using a cyclonic collector in two groups of 7 week-old pigs that were experimentally infected by exposure with a contact infected pig (seeder pig). After contact exposure, individual pig nasal swab samples were collected daily and air samples were collected three times per day for 8 days. All samples were tested for influenza by real-time reverse transcriptase (RRT)-PCR targeting the influenza virus matrix gene. All pigs' nasal swabs became influenza virus RRT-PCR positive upon exposure to the infected seeder pig. Airborne influenza was detected in 28/43 (65%) air samples. The temporal dynamics of influenza virus detection in air samples was in close agreement with the nasal shedding pattern in the infected pigs. First detection of positive bioaerosols happened at 1 day post contact (DPC). Positive bioaerosols were consistently detected between 3 and 6 DPC, a time when most pigs were also shedding virus in nasal secretions. Overall, the odds of detecting a positive air sample increased 2.2 times for every additional nasal swab positive pig in the group. In summary, there was a strong relationship between the number of pigs shedding influenza virus in nasal secretions and the generation of bioaerosols during the course of an acute infection.",,"['Corzo, Cesar A.', 'Romagosa, Anna', 'Dee, Scott', 'Gramer, Marie', 'Morrison, Robert B', 'Torremorell, Montserrat']",,,,
,PMC,"Factors influencing the provision of public health services by village doctors in Hubei and Jiangxi provinces, China",http://dx.doi.org/10.2471/BLT.12.109447,PMC3537250,,,"PROBLEM: The Chinese central government launched the Health System Reform Plan in 2009 to strengthen disease control and health promotion and provide a package of basic public health services. Village doctors receive a modest subsidy for providing public health services associated with the package. Their beliefs about this subsidy and providing public health services could influence the quality and effectiveness of preventive health services and disease surveillance. APPROACH: To understand village doctors’ perspectives on the subsidy and their experiences of delivering public health services, we performed 10 focus group discussions with village doctors, 12 in-depth interviews with directors of township health centres and 4 in-depth interviews with directors of county-level Centers for Disease Control and Prevention. LOCAL SETTING: The study was conducted in four counties in central China, two in Hubei province and two in Jiangxi province. RELEVANT CHANGES: Village doctors prioritize medical services but they do their best to manage their time to include public health services. The willingness of township health centre directors and village doctors to provide public health services has improved since the introduction of the package and a minimum subsidy, but village doctors do not find the subsidy to be sufficient remuneration for their efforts. LESSONS LEARNT: Improving the delivery of public health services by village doctors is likely to require an increase in the subsidy, improvement in the supervisory relationship between village clinics and township health centres and the creation of a government pension for village doctors.",,"['Ding, Yan', 'Smith, Helen J', 'Fei, Yang', 'Xu, Biao', 'Nie, Shaofa', 'Yan, Weirong', 'Diwan, Vinod K', 'Sauerborn, Rainer', 'Dong, Hengjin']",,,,
,PMC,Cyclin D1 overexpression supports stable EBV infection in nasopharyngeal epithelial cells,http://dx.doi.org/10.1073/pnas.1202637109,PMC3528537,,,"Undifferentiated nasopharyngeal carcinomas (NPCs) are commonly present with latent EBV infection. However, events regulating EBV infection at early stages of the disease and the role of EBV in disease pathogenesis are largely undefined. Genetic alterations leading to activation of cyclin D1 signaling in premalignant nasopharyngeal epithelial (NPE) cells have been postulated to predispose cells to EBV infection. We previously reported that loss of p16, a negative regulator of cyclin D1 signaling, is a frequent feature of NPC tumors. Here, we report that early premalignant lesions of nasopharyngeal epithelium overexpress cyclin D1. Furthermore, overexpression of cyclin D1 is closely associated with EBV infection. Therefore we investigated the potential role of cyclin D1 overexpression in dysplastic NPE cells in vitro. In human telomerase reverse transcriptase-immortalized NPE cells, overexpression of cyclin D1 or a p16-resistant form of CDK4 (CDK4(R24C)) suppressed differentiation. This suppression may have implications for the close association of EBV infection with undifferentiated NPC. In these in vitro models, we found that cellular growth arrest and senescence occurred in EBV-infected cell populations immediately after infection. Nevertheless, overexpression of cyclin D1 or a p16-resistant form of CDK4 or knockdown of p16 in the human telomerase reverse transcriptase-immortalized NPE cell lines could counteract the EBV-induced growth arrest and senescence. We conclude that dysregulated expression of cyclin D1 in NPE cells may contribute to NPC pathogenesis by enabling persistent infection of EBV.",,"['Tsang, Chi Man', 'Yip, Yim Ling', 'Lo, Kwok Wai', 'Deng, Wen', 'To, Ka Fai', 'Hau, Pok Man', 'Lau, Victoria Ming Yi', 'Takada, Kenzo', 'Lui, Vivian Wai Yan', 'Lung, Maria Li', 'Chen, Honglin', 'Zeng, Musheng', 'Middeldorp, Jaap Michiel', 'Cheung, Annie Lai-Man', 'Tsao, Sai Wah']",,,,
,PMC,Using Sensor Networks to Study the Effect of Peripatetic Healthcare Workers on the Spread of Hospital-Associated Infections,http://dx.doi.org/10.1093/infdis/jis542,PMC3475631,,,"Background. Super-spreading events, in which an individual with measurably high connectivity is responsible for infecting a large number of people, have been observed. Our goal is to determine the impact of hand hygiene noncompliance among peripatetic (eg, highly mobile or highly connected) healthcare workers compared with less-connected workers. Methods. We used a mote-based sensor network to record contacts among healthcare workers and patients in a 20-bed intensive care unit. The data collected from this network form the basis for an agent-based simulation to model the spread of nosocomial pathogens with various transmission probabilities. We identified the most- and least-connected healthcare workers. We then compared the effects of hand hygiene noncompliance as a function of connectedness. Results. The data confirm the presence of peripatetic healthcare workers. Also, agent-based simulations using our real contact network data confirm that the average number of infected patients was significantly higher when the most connected healthcare worker did not practice hand hygiene and significantly lower when the least connected healthcare workers were noncompliant. Conclusions. Heterogeneity in healthcare worker contact patterns dramatically affects disease diffusion. Our findings should inform future infection control interventions and encourage the application of social network analysis to study disease transmission in healthcare settings.",,"['Hornbeck, Thomas', 'Naylor, David', 'Segre, Alberto M.', 'Thomas, Geb', 'Herman, Ted', 'Polgreen, Philip M.']",,,,
,PMC,IMPACT OF ACE2 DEFICIENCY AND OXIDATIVE STRESS ON CEREBROVASCULAR FUNCTION WITH AGING,http://dx.doi.org/10.1161/STROKEAHA.112.667063,PMC3529166,,,"BACKGROUND AND PURPOSE: Angiotensin II produces oxidative stress and endothelial dysfunction in cerebral arteries, and angiotensin II type I receptors may play a role in longevity and vascular aging. Angiotensin converting enzyme type 2 (ACE2) converts angiotensin II to angiotensin (1–7) and thus may protect against effects of angiotensin II. We hypothesized that ACE2 deficiency increases oxidative stress and endothelial dysfunction in cerebral arteries, and examined the role of ACE2 in age-related cerebrovascular dysfunction. METHODS: Endothelial function, expression of angiotensin system components, NADPH oxidase subunits, and proinflammatory cytokines were examined in cerebral arteries from adult [12 mo old] and old [24 mo old] ACE2 knockout (KO) and wild type (WT) mice. The superoxide scavenger tempol was used to examine the role of oxidative stress on endothelial function. RESULTS: Vasodilatation to acetylcholine was impaired in adult ACE2 KO [24±6% (mean +/− SE)] compared to WT mice [52±7%, p<0.05]. In old mice, vasodilatation to acetylcholine was impaired in WT mice [29±6%] and severely impaired in ACE2 KO mice [7±5%]. Tempol improved endothelial function in adult and old ACE2 KO and WT mice. Aging increased mRNA for TNFα in WT mice, and significantly increased mRNA levels of Nox2, p47(phox), and Rcan1 in both ACE2 KO and WT mice. mRNA levels of angiotensin system components did not change during aging. CONCLUSIONS: ACE2 deficiency impaired endothelial function in cerebral arteries from adult mice and augmented endothelial dysfunction during aging. Oxidative stress plays a critical role in cerebrovascular dysfunction induced by ACE2 deficiency and aging.",,"['Peña Silva, Ricardo A.', 'Chu, Yi', 'Miller, Jordan D.', 'Mitchell, Ian J.', 'Penninger, Josef M.', 'Faraci, Frank M.', 'Heistad, Donald D.']",,,,
,PMC,Multifunctional immune responses of HMBPP-specific Vγ2Vδ2 T cells in M. tuberculosis and other infections,http://dx.doi.org/10.1038/cmi.2012.46,PMC3664056,,,"Vγ2Vδ2 T (also known as Vγ9Vδ2 T) cells exist only in primates, and in humans represent a major γδ T-cell sub-population in the total population of circulating γδ T cells. Results from recent studies suggest that while (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) phosphoantigen from Mycobacterium tuberculosis (Mtb) and other microbes activates and expands primate Vγ2Vδ2 T cells, the Vγ2Vδ2 T-cell receptor (TCR) recognizes and binds to HMBPP on antigen-presenting cells (APC). In response to HMBPP stimulus, Vγ2Vδ2 TCRs array to form signaling-related nanoclusters or nanodomains during the activation of Vγ2Vδ2 T cells. Primary infections with HMBPP-producing pathogens drive the evolution of multieffector functional responses in Vγ2Vδ2 T cells, although Vγ2Vδ2 T cells display different patterns of responses during the acute and chronic phases of Mtb infection and in other infections. Expanded Vγ2Vδ2 T cells in primary Mtb infection can exhibit a broader TCR repertoire and a greater clonal response than previously assumed, with different distribution patterns of Vγ2Vδ2 T-cell clones in lymphoid and non-lymphoid compartments. Emerging in vivo data suggest that HMBPP activation of Vγ2Vδ2 T cells appears to impact other immune cells during infection.",,"Chen, Zheng W",,,,
,PMC,Protein-disulfide Isomerase Regulates the Thyroid Hormone Receptor-mediated Gene Expression via Redox Factor-1 through Thiol Reduction-Oxidation,http://dx.doi.org/10.1074/jbc.M112.365239,PMC3548481,,,"Protein-disulfide isomerase (PDI) is a dithiol/disulfide oxidoreductase that regulates the redox state of proteins. We previously found that overexpression of PDI in rat pituitary tumor (GH3) cells suppresses 3,3′,5-triiodothyronine (T(3))-stimulated growth hormone (GH) expression, suggesting the contribution of PDI to the T(3)-mediated gene expression via thyroid hormone receptor (TR). In the present study, we have clarified the mechanism of regulation by which TR function is regulated by PDI. Overexpression of wild-type but not redox-inactive mutant PDI suppressed the T(3)-induced GH expression, suggesting that the redox activity of PDI contributes to the suppression of GH. We considered that PDI regulates the redox state of the TR and focused on redox factor-1 (Ref-1) as a mediator of the redox regulation of TR by PDI. Interaction between Ref-1 and TRβ1 was detected. Overexpression of wild-type but not C64S Ref-1 facilitated the GH expression, suggesting that redox activity of Cys-64 in Ref-1 is involved in the TR-mediated gene expression. Moreover, PDI interacted with Ref-1 and changed the redox state of Ref-1, suggesting that PDI controls the redox state of Ref-1. Our studies suggested that Ref-1 contributes to TR-mediated gene expression and that the redox state of Ref-1 is regulated by PDI. Redox regulation of PDI via Ref-1 is a new aspect of PDI function.",,"['Hashimoto, Shoko', 'Imaoka, Susumu']",,,,
,PMC,Variable evolutionary routes to host establishment across repeated rabies virus host shifts among bats,http://dx.doi.org/10.1073/pnas.1203456109,PMC3511767,,,"Determining the genetic pathways that viruses traverse to establish in new host species is crucial to predict the outcome of cross-species transmission but poorly understood for most host–virus systems. Using sequences encoding 78% of the rabies virus genome, we explored the extent, repeatability and dynamic outcome of evolution associated with multiple host shifts among New World bats. Episodic bursts of positive selection were detected in several viral proteins, including regions associated with host cell interaction and viral replication. Host shifts involved unique sets of substitutions, and few sites exhibited repeated evolution across adaptation to many bat species, suggesting diverse genetic determinants over host range. Combining these results with genetic reconstructions of the demographic histories of individual viral lineages revealed that although rabies viruses shared consistent three-stage processes of emergence in each new bat species, host shifts involving greater numbers of positively selected substitutions had longer delays between cross-species transmission and enzootic viral establishment. Our results point to multiple evolutionary routes to host establishment in a zoonotic RNA virus that may influence the speed of viral emergence.",,"['Streicker, Daniel G.', 'Altizer, Sonia M.', 'Velasco-Villa, Andrés', 'Rupprecht, Charles E.']",,,,
,PMC,Safety and Immunogenicity of Recombinant Rift Valley Fever MP-12 Vaccine Candidates in Sheep,http://dx.doi.org/10.1016/j.vaccine.2012.10.118,PMC3534907,,,"The safety and immunogenicity of two authentic recombinant (ar) Rift Valley Fever (RVF) viruses, one with a deletion in the NSs region of the S RNA segment (arMP-12ΔNSs16/198) and the other with a large deletion of the NSm gene in the pre Gn region of the M RNA segment (arMP-12ΔNSm21/384) of the RVF MP-12 vaccine virus were tested in crossbred ewes at 30 – 50 days of gestation. First, we evaluated the neutralizing antibody response, measured by plaque reduction neutralization (PRNT(80)), and clinical response of the two viruses in groups of four ewes each. The virus dose was 1 × 10(5) plaque forming units (PFU). Control groups of four ewes each were also inoculated with a similar dose of RVF MP-12 or the parent recombinant virus (arMP-12). Neutralizing antibody was first detected in 3 of 4 animals inoculated with arMP-12ΔNSm21/384 on day 5 post inoculation and all four animals had PRNT(80) titers of ≥ 1:20 on day 6. Neutralizing antibody was first detected in 2 of 4 ewes inoculated with arMP-12ΔNSs16/198 on day 7 and all had PRNT(80) titers of ≥ 1:20 on day 10. We found the mean PRNT(80) response to arMP-12ΔNSs16/198 to be 16- to 25-fold lower than that of ewes inoculated with arMP-12ΔNSm21/384, arMP-12 or RVF MP-12. No abortions occurred though a single fetal death in each of the arMP-12 and RVF MP-12 groups was found at necropsy. The poor PRNT(80) response to arMP-12ΔNSs16/198 caused us to discontinue further testing of this candidate and focus on arMP-12ΔNSm21/384. A dose escalation study of arMP-12ΔNSm21/384, showed that 1 × 10(3) plaque forming units (PFU) stimulates a PRNT(80) response comparable to doses of up to 1 × 10(5) PFU of this virus. With further study, the arMP-12ΔNSm21/384 virus may prove to be a safe and efficacious candidate for a livestock vaccine. The large deletion in the NSm gene may also provide a negative marker that will allow serologic differentiation of naturally infected animals from vaccinated animals.",,"['Morrill, John C.', 'Laughlin, Richard C.', 'Lokugamage, Nandadeva', 'Pugh, Roberta', 'Sbrana, Elena', 'Weise, William J.', 'Adams, L. Garry', 'Makino, Shinji', 'Peters, C. J.']",,,,
,PMC,"Human rhinovirus C: Age, season, and lower respiratory illness over the past 3 decades",http://dx.doi.org/10.1016/j.jaci.2012.09.033,PMC3748586,,,"BACKGROUND: Human rhinoviruses (HRVs) cause common colds, and the recently discovered HRV-C is increasingly associated with lower respiratory illness among populations such as children and asthmatic patients. OBJECTIVE: To determine how HRV-C is associated with respiratory illness and to evaluate changes in prevalence and species over 2 decades. METHODS: A prospective study of children younger than 5 years was performed at the Vanderbilt Vaccine Clinic over a 21-year period. Nasal-wash specimens from children presenting with upper or lower respiratory illness at acute care visits were tested for HRV and HRV-positives genotyped. Demographic and clinical features were compared between children with or without HRV, and with different HRV species. RESULTS: HRV was detected in 190 of 527 (36%) specimens from a population of 2009 children from 1982 through 2003. Of these, 36% were HRV-C. Age (P = .039) and month of illness (P <.001) were associated with HRV infection and HRV species. HRV-C was significantly associated with lower respiratory illness, compared with HRV-A (P = .014). HRV-A and HRV-C prevalence fluctuated throughout the 21-year period; HRV-C was more prevalent during winter (P = .058). CONCLUSIONS: HRV-C is not a new virus but has been significantly associated with childhood lower respiratory illness in this population for several decades. Temporal changes in virus prevalence occur, and season may predict virus species. Our findings have implications for diagnostic, preventive, and treatment strategies due to the variation in disease season and severity based on species of HRV infection.",,"['Linder, Jodell E.', 'Kraft, David C.', 'Mohamed, Yassir', 'Lu, Zengqi', 'Heil, Luke', 'Tollefson, Sharon', 'Saville, Benjamin R.', 'Wright, Peter F.', 'Williams, John V.', 'Miller, E. Kathryn']",,,,
,PMC,SARS-like virus in the Middle East: A truly bat-related coronavirus causing human diseases,http://dx.doi.org/10.1007/s13238-012-2811-1,PMC4875465,,,,,"['Lu, Guangwen', 'Liu, Di']",,,,
,PMC,"(1)H, (13)C, (15)N resonance assignments of murine hepatitis virus nonstructural protein 3a",http://dx.doi.org/10.1007/s12104-012-9443-5,PMC3587040,,,"Nonstructural protein (nsp) 3 is the largest of 16 nsps translated from the murine hepatitis virus (MHV) genome. The N-terminal most domain of nsp3, nsp3a, has been identified by reverse genetics as a likely binding partner of MHV nucleocapsid protein. Here we report the backbone and side chain resonance assignments of MHV nsp3a (residues 1–114).",,"['Keane, Sarah C.', 'Giedroc, David P.']",,,,
,PMC,The Functional Protein Microarray as Molecular Decathlete: A Versatile Player in Clinical Proteomics,http://dx.doi.org/10.1002/prca.201200041,PMC3600421,,,,,"['Zhu, Heng', 'Cox, Eric', 'Qian, Jiang']",,,,
,PMC,Substrate Specificity of Tulane Virus Protease,http://dx.doi.org/10.1016/j.virol.2012.10.010,PMC3545077,,,"Tulane virus (TV) is a cultivable calicivirus isolated from rhesus monkeys. In this study, we characterized the substrate specificity of TV protease in trans using recombinant proteases and TV polyprotein fragments containing the predicted proteolytic cleavage sites. Cleavage products have been obtained from 4 of the 5 fragments containing (573)Q-S(574) between the helicase and 3A-like protein, (712)E-A(713) between the 3A-like protein and Vpg, (802)E-G(803) between Vpg and the protease, and (976)E-G(977) between the protease and RdRp. We also characterized the enzymatic activities of the recombinant proteases of TV and Norwalk virus using synthetic fluorogenic peptide substrates. Under optimal conditions for enzymatic assays, partial cross-reactivities on reciprocal substrates were observed between TV and Norwalk virus proteases. The apparently shared substrate specificities between TV and Norwalk virus proteases suggested that the cultivable TV could be used as a model for in vivo evaluation of lead candidates of protease inhibitors for human norovirus.",,"['Wei, Chao', 'Meller, Jarek', 'Jiang, Xi']",,,,
,PMC,Colorimetric viral detection based on sialic acid stabilized gold nanoparticles,http://dx.doi.org/10.1016/j.bios.2012.10.067,PMC3964789,,,"Sialic acid reduced and stabilized gold nanoparticles (d = 20.1 ± 1.8 nm) were synthesized by a simple one-pot, green method without chemically modifying sialic acid for colorimetric detection of influenza virus. The gold nanoparticles showed target-specific aggregation with viral particles via hemagglutinin-sialic acid binding. A linear correlation was observed between the change in optical density and dilution of chemically inactivated influenza B/Victoria and influenza B/Yamagata. Virus dilution (hemagglutinination assay titer, 512) of 0.156 vol% was readily detected. The upper limit of the linearity can be extended with the use of more sialic acid-gold nanoparticles.",,"['Lee, Changwon', 'Gaston, Marsha A.', 'Weiss, Alison A.', 'Zhang, Peng']",,,,
,PMC,Autoregulation of thromboinflammation on biomaterial surfaces by a multicomponent therapeutic coating,http://dx.doi.org/10.1016/j.biomaterials.2012.10.040,PMC4705352,,,"Activation of the thrombotic and complement systems is the main recognition and effector mechanisms in the multiple adverse biological responses triggered when biomaterials or therapeutic cells come into blood contact. We have created a surface which is auto-protective to human innate immunity by combining three fundamentally different strategies, all developed by us previously, which have been shown to induce substantial, but incomplete hemocompatibility when used separately. In summary, we have conjugated a factor H –binding peptide; and an ADP-degrading enzyme; using a PEG linker on both material and cellular surfaces. When exposed to human whole blood, factor H was specifically recruited to the modified surfaces and inhibited complement attack. In addition, activation of platelets and coagulation was efficiently attenuated, by degrading ADP. Thus, by inhibiting thromboinflammation using a multicomponent approach, we have created a hybrid surface with the potential to greatly reduce incompatibility reactions involving biomaterials and transplantation.",,"['Nilsson, Per H', 'Ekdahl, Kristina N', 'Magnusson, Peetra U', 'Qu, Hongchang', 'Iwata, Hiroo', 'Ricklin, Daniel', 'Hong, Jaan', 'Lambris, John D', 'Nilsson, Bo', 'Teramura, Yuji']",,,,
,PMC,Palmitate-derivatized human IL-2: a potential anti-cancer immunotherapeutic of low systemic toxicity,http://dx.doi.org/10.1007/s00262-012-1364-8,PMC4393711,,,"PURPOSE AND EXPERIMENTAL DESIGN: Recombinant human IL-2 (rhIL-2) is a potent cytokine and FDA-approved anti-cancer drug. However, its clinical use has been limited by severe toxicity, associated primarily with systemic administration with excess protein distributing freely throughout the body. We hypothesized that rhIL-2 in alternate forms permitting more restricted localization may exert stronger antitumor efficacy and less toxicity. Here, we have tested the utility of palmitate-derivatized rhIL-2. rhIL-2 was reacted with N-hydroxysuccinimide palmitate ester. The resultant lipidated rhIL-2 (pIL-2), when mixed with cells, could spontaneously transfer from solution to cell surfaces. Next, anticancer efficacy of pIL-2 was assessed in two modalities. For adoptive T cell therapy, antitumor cytotoxic T cells (CTLs) were protein transferred (“painted”) with pIL-2 and injected into mice bearing lymphoma. For in situ therapy, pIL-2 was injected intratumorally into mice bearing melanoma. Tumor growth and IL-2-associated toxicity were determined. RESULTS: In the lymphoma model, painting of the antitumor CTLs with pIL-2 markedly increased their viability and titer. In the melanoma model, intratumoral injection of pIL-2, but not rhIL-2, increased the number of activated CD8(+) T cells (IFN-γ(+)) in the spleen, reduced lung metastasis and prolonged the survival of treated mice. Moreover, while repeated intratumoral injection of rhIL-2 at an excessively high dose (10 injections of 10000 IU/mouse) caused marked vascular leakage syndrome, the same regimen using pIL-2 caused no detectable toxicity. CONCLUSIONS: Transferring spontaneously from solution to cell surfaces, pIL-2 may bypass the current limitations of rhIL-2 and, thus, serve as a more effective and tolerable anticancer drug.",,"['Chou, Sharon H.', 'Shetty, Aditya V.', 'Geng, Yajun', 'Xu, Lipeng', 'Munirathinam, Gnanasekar', 'Pipathsouk, Anne', 'Tan, Isaiah', 'Morris, Timothy', 'Wang, Bin', 'Chen, Aoshuang', 'Zheng, Guoxing']",,,,
,PMC,CD11c(+)/CD11b(+) Cells Are Critical for Organic Dust–Elicited Murine Lung Inflammation,http://dx.doi.org/10.1165/rcmb.2012-0095OC,PMC3547108,,,"Organic dust exposure in the agricultural industry results in significant lung disease. Macrophage infiltrates are increased in the lungs after organic dust exposures, yet the phenotype and functional importance of these cells remain unclear. Using an established intranasal inhalation murine model of dust-induced lung inflammation, animals were treated once or daily for 3 weeks with swine confinement organic dust extract (DE). Repetitive DE treatment for 3 weeks resulted in significant increases in CD11c(+)/CD11b(+) macrophages in whole lung–associated tissue. These cells displayed increased costimulatory molecule (CD80 and CD86) expression, enhanced phagocytic ability, and an increased production of IL-6, CXCL1, and CXCL2. Similar findings were observed with the CD11c(+)/CD11b(+) macrophage infiltrate after repetitive exposure to peptidoglycan, a major DE component. To determine the functional importance of macrophages in mediating DE-induced airway inflammation, lung macrophages were selectively depleted using a well-established intranasal clodronate liposome depletion/suicide strategy. First, macrophage depletion by clodronate liposomes resulted in significant reductions in airway neutrophil influx and TNF-α and IL-6 production after a single exposure to DE. In contrast, after repetitive 3-week exposure to DE, airway lavage fluid and lung tissue neutrophils were significantly increased in clodronate liposome–treated mice compared with control mice. A histological examination of lung tissue demonstrated striking increases in alveolar and bronchiolar inflammation, as well as in the size and distribution of cellular aggregates in clodronate–liposome versus saline–liposome groups repetitively exposed to DE. These studies demonstrate that DE elicits activated CD11c(+)/CD11b(+) macrophages in the lung, which play a critical role in regulating the outcome of DE-induced airway inflammation.",,"['Poole, Jill A.', 'Gleason, Angela M.', 'Bauer, Christopher', 'West, William W.', 'Alexis, Neil', 'van Rooijen, Nico', 'Reynolds, Stephen J.', 'Romberger, Debra J.', 'Kielian, Tammy L.']",,,,
,PMC,Evaluation of Sample Recovery Efficiency for Bacteriophage P22 on Fomites,http://dx.doi.org/10.1128/AEM.01370-12,PMC3485962,,,"Fomites are known to play a role in the transmission of pathogens. Quantitative analysis of the parameters that affect sample recovery efficiency (SRE) at the limit of detection of viruses on fomites will aid in improving quantitative microbial risk assessment (QMRA) and infection control. The variability in SRE as a function of fomite type, fomite surface area, sampling time, application media, relative humidity (rH), and wetting agent was evaluated. To quantify the SRE, bacteriophage P22 was applied onto fomites at average surface densities of 0.4 ± 0.2 and 4 ± 2 PFU/cm(2). Surface areas of 100 and 1,000 cm(2) of nonporous fomites found in indoor environments (acrylic, galvanized steel, and laminate) were evaluated with premoistened antistatic wipes. The parameters with the most effects on the SRE were sampling time, fomite surface area, wetting agent, and rH. At time zero (the initial application of bacteriophage P22), the SRE for the 1,000-cm(2) fomite surface area was, on average, 40% lower than that for the 100-cm(2) fomite surface area. For both fomite surface areas, the application medium Trypticase soy broth (TSB) and/or the laminate fomite predominantly resulted in a higher SRE. After the applied samples dried on the fomites (20 min), the average SRE was less than 3%. A TSB wetting agent applied on the fomite improved the SRE for all samples at 20 min. In addition, an rH greater than 28% generally resulted in a higher SRE than an rH less than 28%. The parameters impacting SRE at the limit of detection have the potential to enhance sampling strategies and data collection for QMRA models.",,"['Herzog, Amanda B.', 'Pandey, Alok K.', 'Reyes-Gastelum, David', 'Gerba, Charles P.', 'Rose, Joan B.', 'Hashsham, Syed A.']",,,,
,PMC,High-Density Lipoprotein and 4F Peptide Reduce Systemic Inflammation by Modulating Intestinal Oxidized Lipid Metabolism: Novel Hypotheses and Review of Literature,http://dx.doi.org/10.1161/ATVBAHA.112.300282,PMC3597084,,,"Oxidized phospholipids are found in the vasculature of animal models of atherosclerosis, in human atherosclerotic lesions, and in other inflammatory diseases. Oxidized phospholipids cause vascular and nonvascular cells to initiate an inflammatory reaction. Metabolites of arachidonic acid, such as 12-hydroxyeicosatetraenoic acid, can mimic some of the inflammatory properties of oxidized phospholipids. In vitro and in vivo normal high-density lipoprotein (HDL), normal apolipoprotein A-I, and apolipoprotein A-I mimetic peptides, each likely acting in a different manner, prevent the inflammatory reaction characteristic of atherosclerosis, and this is associated with decreased levels of oxidized lipids in tissues and cells. HDL from animal models of atherosclerosis or from humans with atherosclerosis or from humans or animals with other chronic inflammatory diseases does not prevent the inflammatory reaction characteristic of atherosclerosis and may even enhance the inflammatory reaction. In mice and perhaps humans, ≈30% of the steady-state plasma HDL-cholesterol pool is derived from the small intestine. The metabolism of phospholipids by gut bacteria has been recently implicated in atherosclerosis in both mice and humans. Studies with apolipoprotein A-I mimetic peptides suggest that the small intestine is a major tissue regulating systemic inflammation in mouse models of atherosclerosis and may be important for determining the functionality of HDL.",,"['Navab, Mohamad', 'Reddy, Srinivasa T.', 'Van Lenten, Brian J.', 'Buga, Georgette M.', 'Hough, Greg', 'Wagner, Alan C.', 'Fogelman, Alan M.']",,,,
,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.12.011112,PMC3506401,,,,,,,,,
,PMC,"Blood cytokine, chemokine and gene expression in cholestasis patients with intractable pruritus treated with a molecular adsorbent recirculating system: A case series",,PMC3495697,,,"BACKGROUND: The molecular adsorbent recirculating system (MARS) is an albumin-dialysis modality that has been investigated predominantly in patients with acute and acute-on-chronic liver failure. OBJECTIVES: To report the clinical efficacy and safety of MARS therapy for intractable pruritus in cholestasis patients with stable chronic liver disease, characterizing the impact of MARS on cytokine levels and on the transcriptome in the blood compartment. METHODS: MARS therapy was performed on three patients with cholestatic liver disease using 8 h runs for two consecutive days. The expression levels of 65 cytokines/chemokines and 24,000 genes were profiled by Luminex (Luminex Corporation, USA) and microarray, respectively. RESULTS: A quality-of-life assessment demonstrated a marked improvement during therapy, which was sustained in two of three patients. No bleeding or infectious complications were observed. Bile acid levels were markedly reduced following MARS (mean [± SD] pretreatment 478.9±112.2 μmol/L versus post-treatment 89.7±68.8 μmol/L). Concordant decreases in cytokine/chemokine levels were noted for interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-12 (p40), RANTES, tranforming growth factor-alpha, tumour necrosis factor-alpha and thrombopoietin following MARS. On microarray profiling, biologically relevant concordant changes among all patients were evident for 20 different genes (10 upregulated and 10 downregulated). The upregulation of several potentially immune suppressive/regulatory genes (eg, early growth response 3 [EGR-3], ephrin-A2 [EFNA2] and serum amyloid A1 [SAA1]), concurrent with downregulation of genes involved in innate immunity (eg, toll-like receptor 4 interactor with leucine-rich repeats [TRIL]) and inflammation (eg, ephrin receptor B1 [EPHB1]), was observed. CONCLUSIONS: This investigative approach offers new insights into intractable pruritus and suggests future therapeutic targets. The clinical benefit of MARS in cholestasis patients with intractable pruritus may not exclusively result from filtration of pruritogens, but also from systemic changes in cytokine/chemokine levels and changes in gene expression of blood cells.",,"['Lisboa, Luiz F', 'Asthana, Sonal', 'Kremer, Andreas E', 'Swain, Mark', 'Bagshaw, Sean M', 'Gibney, Noel', 'Karvellas, Constantine J']",,,,
,PMC,Public Health Watch,http://dx.doi.org/10.3821/145.6.cpj248,PMC3567591,,,,,"Lynas, Kathie",,,,
,PMC,Influenza Virus H5 DNA Vaccination Is Immunogenic by Intramuscular and Intradermal Routes in Humans,http://dx.doi.org/10.1128/CVI.05663-11,PMC3491556,,,"Avian influenza virus causes outbreaks in domestic and wild birds around the world, and sporadic human infections have been reported. A DNA vaccine encoding hemagglutinin (HA) protein from the A/Indonesia/5/05 (H5N1) strain was initially tested in two randomized phase I clinical studies. Vaccine Research Center study 304 (VRC 304) was a double-blinded study with 45 subjects randomized to placebo, 1 mg of vaccine, or 4 mg of vaccine treatment groups (n = 15/group) by intramuscular (i.m.) Biojector injection. VRC 305 was an open-label study to evaluate route, with 44 subjects randomized to intradermal (i.d.) injections of 0.5 mg by needle/syringe or by Biojector or 1 mg delivered as two 0.5-mg Biojector injections in the same deltoid or as 0.5 mg in each deltoid (n = 11/group). Injections were administered at weeks 0, 4, and 8 in both studies. Antibody responses to H5 were assessed by hemagglutination inhibition (HAI) assay, enzyme-linked immunosorbent assay (ELISA), and neutralization assay, and the H5 T cell responses were assessed by enzyme-linked immunospot and intracellular cytokine staining assays. There were no vaccine-related serious adverse events, and the vaccine was well tolerated in all groups. At 1 mg, i.d. vaccination compared to i.m. vaccination induced a greater frequency and magnitude of response by ELISA, but there were no significant differences in the frequency or magnitude of response between the i.d. and i.m. routes in the HAI or neutralization assays. T cell responses were more common in subjects who received the 1- or 4-mg dose i.m. These studies demonstrated that the DNA vaccine encoding H5 is safe and immunogenic and served to define the proper dose and route for further studies. The i.d. injection route did not offer a significant advantage over the i.m. route, and no difference was detected by delivery to one site versus splitting the dose between two sites for i.d. vaccine administration. The 4-mg dose (i.m) was further investigated in prime-boost regimens.",,"['Ledgerwood, J. E.', 'Hu, Z.', 'Gordon, I. J.', 'Yamshchikov, G.', 'Enama, M. E.', 'Plummer, S.', 'Bailer, R.', 'Pearce, M. B.', 'Tumpey, T. M.', 'Koup, R. A.', 'Mascola, J. R.', 'Nabel, G. J.', 'Graham, B. S.']",,,,
,PMC,"Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response",http://dx.doi.org/10.3201/eid/1811.120453,PMC3559169,23092707,NO-CC CODE,"The rapid advancement of genome technologies holds great promise for improving the quality and speed of clinical and public health laboratory investigations and for decreasing their cost. The latest generation of genome DNA sequencers can provide highly detailed and robust information on disease-causing microbes, and in the near future these technologies will be suitable for routine use in national, regional, and global public health laboratories. With additional improvements in instrumentation, these next- or third-generation sequencers are likely to replace conventional culture-based and molecular typing methods to provide point-of-care clinical diagnosis and other essential information for quicker and better treatment of patients. Provided there is free-sharing of information by all clinical and public health laboratories, these genomic tools could spawn a global system of linked databases of pathogen genomes that would ensure more efficient detection, prevention, and control of endemic, emerging, and other infectious disease outbreaks worldwide.",2012 Nov,"['Aarestrup, Frank M.', 'Brown, Eric W.', 'Detter, Chris', 'Gerner-Smidt, Peter', 'Gilmour, Matthew W.', 'Harmsen, Dag', 'Hendriksen, Rene S.', 'Hewson, Roger', 'Heymann, David L.', 'Johansson, Karin', 'Ijaz, Kashef', 'Keim, Paul S.', 'Koopmans, Marion', 'Kroneman, Annelies', 'Wong, Danilo Lo Fo', 'Lund, Ole', 'Palm, Daniel', 'Sawanpanyalert, Pathom', 'Sobel, Jeremy', 'Schlundt, Jørgen']",Emerg Infect Dis,,,
,PMC,Sphingopeptides: dihydrosphingosine-based fusion inhibitors against wild-type and enfuvirtide-resistant HIV-1,http://dx.doi.org/10.1096/fj.12-215111,PMC3475257,,,"Understanding the structural organization of lipids in the cell and viral membranes is essential for elucidating mechanisms of viral fusion that lead to entry of enveloped viruses into their host cells. The HIV lipidome shows a remarkable enrichment in dihydrosphingomyelin, an unusual sphingolipid formed by a dihydrosphingosine backbone. Here we investigated the ability of dihydrosphingosine to incorporate into the site of membrane fusion mediated by the HIV envelope (Env) protein. Dihydrosphingosine as well as cholesterol, fatty acid, and tocopherol was conjugated to highly conserved, short HIV-1 Env-derived peptides with no antiviral activity otherwise. We showed that dihydrosphingosine exclusively endowed nanomolar antiviral activity to the peptides (IC(50) as low as 120 nM) in HIV-1 infection on TZM-bl cells and on Jurkat T cells, as well as in the cell-cell fusion assay. These sphingopeptides were active against enfuvirtide-resistant and wild-type CXCR4 and CCR5 tropic HIV strains. The anti-HIV activity was determined by both the peptides and their dihydrosphingosine conjugate. Moreover, their mode of action involved accumulation in the cells and viruses and binding to membranes enriched in sphingomyelin and cholesterol. The data suggest that sphingopeptides are recruited to the HIV membrane fusion site and provide a general concept in developing inhibitors of sphingolipid-mediated biological systems.—Ashkenazi, A., Viard, M., Unger, L., Blumenthal, R., Shai, Y. Sphingopeptides: dihydrosphingosine-based fusion inhibitors against wild-type and enfuvirtide-resistant HIV-1.",,"['Ashkenazi, Avraham', 'Viard, Mathias', 'Unger, Linor', 'Blumenthal, Robert', 'Shai, Yechiel']",,,,
,PMC,Role of T-cell epitope-based vaccine in prophylactic and therapeutic applications,http://dx.doi.org/10.2217/fvl.12.108,PMC3636528,,,"Prophylactic and therapeutic vaccines against viral infections have advanced in recent years from attenuated live vaccines to subunit-based vaccines. An ideal prophylactic vaccine should mimic the natural immunity induced by an infection, in that it should generate long-lasting adaptive immunity. To complement subunit vaccines, which primarily target an antibody response, different methodologies are being investigated to develop vaccines capable of driving cellular immunity. T-cell epitope discovery is central to this concept. In this review, the significance of T-cell epitope-based vaccines for prophylactic and therapeutic applications is discussed. Additionally, methodologies for the discovery of T-cell epitopes, as well as recent developments in the clinical testing of these vaccines for various viral infections, are explained.",,"['Testa, James S', 'Philip, Ramila']",,,,
,PMC,The Short isoform of the CEACAM1 receptor in intestinal T cells regulates mucosal immunity and homeostasis via Tfh cell induction,http://dx.doi.org/10.1016/j.immuni.2012.07.016,PMC3516394,,,"Carcinoembryonic antigen cell adhesion molecule like I (CEACAM1) is expressed on activated T cells and signals through either a long (L) cytoplasmic tail containing immune receptor tyrosine based inhibitory motifs, which provide inhibitory function, or a short (S) cytoplasmic tail with an unknown role. Previous studies on peripheral T cells show that CEACAM1-L isoforms predominate with little to no detectable CEACAM1-S isoforms in mouse and human. We show here that this was not the case in tissue resident T cells of intestines and gut associated lymphoid tissues which demonstrated predominant expression of CEACAM1-S isoforms relative to CEACAM1-L isoforms in human and mouse. This tissue resident predominance of CEACAM1-S expression was determined by the intestinal environment where it served a stimulatory function leading to the regulation of T cell subsets associated with generation of secretory IgA immunity, the regulation of mucosal commensalism, and defense of the barrier against enteropathogens.",,"['Chen, Lanfen', 'Chen, Zhangguo', 'Baker, Kristi', 'Halvorsen, E lizabeth M.', 'da Cunha, Andre Pires', 'Flak, Magdalena B.', 'Gerber, Georg', 'Huang, Yu-Hwa', 'Hosomi, Shuhei', 'Arthur, J anelle C.', 'Dery, Ken J.', 'Nagaishi, Takashi', 'Beauchemin, Nicole', 'Holmes, Kathryn V.', 'Ho, Joshua W. K.', 'Shively, John E.', 'Jobin, Christian', 'Onderdonk, Andrew B.', 'Bry, Lynn', 'Weiner, Howard L.', 'Higgins, Darren E.', 'Blumberg, Richard S.']",,,,
,PMC,Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans,http://dx.doi.org/10.3109/08958378.2012.725782,PMC5119470,,,"The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 μm in size were examined for endotracheal and and up to 5 μm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model.",,"['Asgharian, Bahman', 'Price, Owen', 'McClellan, Gene', 'Corley, Rick', 'Einstein, Daniel R.', 'Jacob, Richard E.', 'Harkema, Jack', 'Carey, Stephan A.', 'Schelegle, Edward', 'Hyde, Dallas', 'Kimbell, Julia S.', 'Miller, Frederick J.']",,,,
,PMC,Concept analysis of professional commitment in Iranian nurses,,PMC3730449,23922592,CC BY-NC-SA,"AIM: Professional commitment has been widely discussed during the last decade. There is no comprehensive definition about “professional commitment in Iranian nurses.” Hence, this study was conducted with the aim of analyzing the concept of professional commitment in Iranian nurses. MATERIALS AND METHODS: Hybrid model was used in three phases. Firstly, in the theoretical phase, data were retrieved from the CINHAl, MEDLINE, PubMed, OVID, Google scholar, and SID databases. The literature search used the keywords “professional commitment” and “nursing.” The final sample included 27 papers published in English between 2001 and 2011.Secondly, in the fieldwork phase, deep interviews with five clinical nurses were carried out, and thirdly, in the final analytical phase, the obtained data from theoretical and fieldwork phases were combined and a comprehensive analysis was conducted. RESULTS: Loyalty and tendency to remain in the profession and responsibility to the professional issues were extracted in theoretical phase. Commitment to promote caring abilities, satisfying of being a nurse, and belonging to the nursing profession were obtained in fieldwork phase. Finally, two main themes including “commitment to offering the best nursing care” and “commitment to promotion of the nursing profession” were extracted. CONCLUSION: Nursing is a humanistic profession; it has some particular characteristics due to the profession’s nature. In this paper, a definition composed of two main dimensions of professional commitment in nursing has been introduced.",2012 Nov-Dec,"['Jafaragaee, Fateme', 'Parvizy, Soroor', 'Mehrdad, Neda', 'Rafii, Forough']",Iran J Nurs Midwifery Res,,,
,PMC,"A Therapeutic Dose of Ketoprofen Causes Acute Gastrointestinal Bleeding, Erosions, and Ulcers in Rats",,PMC3508190,,,"Perioperative treatment of several rats in our facility with ketoprofen (5 mg/kg SC) resulted in blood loss, peritonitis, and death within a day to a little more than a week after surgery that was not related to the gastrointestinal tract. Published reports have established the 5-mg/kg dose as safe and effective for rats. Because ketoprofen is a nonselective nonsteroidal antiinflammatory drug that can damage the gastrointestinal tract, the putative diagnosis for these morbidities and mortalities was gastrointestinal toxicity caused by ketoprofen (5 mg/kg). We conducted a prospective study evaluating the effect of this therapeutic dose of ketoprofen on the rat gastrointestinal tract within 24 h. Ketoprofen (5 mg/kg SC) was administered to one group of rats that then received gas anesthesia for 30 min and to another group without subsequent anesthesia. A third group was injected with saline followed by 30 min of gas anesthesia. Our primary hypothesis was that noteworthy gastrointestinal bleeding and lesions would occur in both groups treated with ketoprofen but not in rats that received saline and anesthesia. Our results showed marked gastrointestinal bleeding, erosions, and small intestinal ulcers in the ketoprofen-treated rats and minimal damages in the saline-treated group. The combination of ketoprofen and anesthesia resulted in worse clinical signs than did ketoprofen alone. We conclude that a single 5-mg/kg dose of ketoprofen causes acute mucosal damage to the rat small intestine.",,"['Shientag, Lisa J', 'Wheeler, Suzanne M', 'Garlick, David S', 'Maranda, Louise S']",,,,
,PMC,Age-Associated Variability in Susceptibility of Swiss Webster Mice to MPV and Other Excluded Murine Pathogens,,PMC3508183,,,"Detection of mouse parvovirus (MPV) and other murine pathogens in research colonies is dependent on the transmissibility of the agents and the sensitivity of sentinels to those agents. Transmissibility is based on several agent-dependent properties including mode of transmission, infectivity, and environmental stability, whereas host susceptibility can vary according to mouse age, strain, and sex. In this study, 4-wk-old, 12-wk-old, and aged Swiss Webster female sentinel mice were compared for their ability to detect infectious agents by using a standardized health surveillance program, to determine whether sentinels should be replaced more frequently to improve the efficiency of detection of infectious agents within a murine colony. Both experimentally and naturally infected mice were used to transmit MPV and other infectious agents from index mice to sentinels. First, Swiss Webster mice were inoculated with MPV, and transmission to 4-, 12-, and 24-wk-old contact and soiled-bedding sentinels was determined. Second, mice naturally infected with 9 infectious agents were obtained from 2 local pet stores, and transmission to 4-wk-old contact sentinels and 4-, 12-, and 44-wk-old soiled-bedding sentinels was determined. For agents that were transmitted via soiled bedding (MPV, mouse hepatitis virus, murine norovirus, Theiler murine encephalomyelitis virus, and pinworms), transmission did not differ in regard to the age of the sentinels. In conclusion, susceptibility to several infectious agents did not differ according to sentinel age in a health-surveillance protocol that used mice older than 12 wk.",,"['Grove, Kristina A', 'Smith, Peter C', 'Booth, Carmen J', 'Compton, Susan R']",,,,
,PMC,Transmission of Mouse Parvovirus by Fomites,,PMC3508181,,,"The goal of the current studies was to determine the risk of transmission of mouse parvovirus (MPV) by caging and husbandry practices. To determine whether MPV can be transmitted during cage changes in a biologic safety cabinet without the use of disinfectants, 14 cages of Swiss Webster mice were inoculated with MPV. Cages containing infected mice were interspersed among 14 cages housing naïve Swiss Webster mice. At 1, 2, and 4 wk after inoculation of the mice, cages were changed across each row. All naïve mice housed adjacent to infected mice remained seronegative. To determine the risk of environmental contamination, nesting pads that were used to sample the room floor during husbandry procedures at 1, 2, 4, and 6 wk after inoculation of the mice were placed in cages with naïve mice. None of the mice exposed to the pads became MPV seropositive. To determine whether components from cages that had housed MPV-infected mice could transmit MPV, Swiss Webster mice were exposed to soiled bedding or used cages, drinking valves, food, cage bottoms, wire bars and filter tops, nesting material, or shelters. With the exception of drinking valves, all mice exposed to other components became MPV seropositive. Fourteen cages that had housed MPV-infected mice were washed but not autoclaved; mice housed in the washed cages did not become MPV seropositive. In conclusion, all cage components can serve as fomites, with the drinking valve being the least risky. Cage washing alone was sufficient to remove or inactivate MPV.",,"['Compton, Susan R', 'Paturzo, Frank X', 'Smith, Peter C', 'Macy, James D']",,,,
,PMC,Sex-Associated Effects on Hematologic and Serum Chemistry Analytes in Sand Rats (Psammomys obesus),,PMC3508180,,,"We sought to determine whether sex had a significant effect on the hematologic and serum chemistry analytes in adult sand rats (Psammomys obesus) maintained under normal laboratory conditions. According to the few data available for this species, we hypothesized that levels of hematologic and serum chemistry analytes would not differ significantly between clinically normal male and female sand rats. Data analysis revealed several significant differences in hematologic parameters between male and female sand rats but none for serum biochemistry analytes. The following hematologic parameters were greater in male than in female sand rats: RBC count, hemoglobin, hematocrit, red cell hemoglobin content, and percentage monocytes. Red cell distribution width, hemoglobin distribution width, mean platelet volume, and percentage lymphocytes were greater in female than in male sand rats. The sex of adult sand rats is a source of variation that must be considered in terms of clinical and research data. The data presented here likely will prove useful in the veterinary medical management of sand rat colonies and provide baseline hematologic and serum chemistry analyte information for researchers wishing to use this species.",,"['Kane, Julie D', 'Steinbach, Thomas J', 'Sturdivant, Rodney X', 'Burks, Robert E']",,,,
,PMC,"Leptospiral Outer Membrane Protein Microarray, a Novel Approach to Identification of Host Ligand-Binding Proteins",http://dx.doi.org/10.1128/JB.01119-12,PMC3486348,,,"Leptospirosis is a zoonosis with worldwide distribution caused by pathogenic spirochetes belonging to the genus Leptospira. The leptospiral life cycle involves transmission via freshwater and colonization of the renal tubules of their reservoir hosts. Infection requires adherence to cell surfaces and extracellular matrix components of host tissues. These host-pathogen interactions involve outer membrane proteins (OMPs) expressed on the bacterial surface. In this study, we developed an Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 OMP microarray containing all predicted lipoproteins and transmembrane OMPs. A total of 401 leptospiral genes or their fragments were transcribed and translated in vitro and printed on nitrocellulose-coated glass slides. We investigated the potential of this protein microarray to screen for interactions between leptospiral OMPs and fibronectin (Fn). This approach resulted in the identification of the recently described fibronectin-binding protein, LIC10258 (MFn8, Lsa66), and 14 novel Fn-binding proteins, denoted Microarray Fn-binding proteins (MFns). We confirmed Fn binding of purified recombinant LIC11612 (MFn1), LIC10714 (MFn2), LIC11051 (MFn6), LIC11436 (MFn7), LIC10258 (MFn8, Lsa66), and LIC10537 (MFn9) by far-Western blot assays. Moreover, we obtained specific antibodies to MFn1, MFn7, MFn8 (Lsa66), and MFn9 and demonstrated that MFn1, MFn7, and MFn9 are expressed and surface exposed under in vitro growth conditions. Further, we demonstrated that MFn1, MFn4 (LIC12631, Sph2), and MFn7 enable leptospires to bind fibronectin when expressed in the saprophyte, Leptospira biflexa. Protein microarrays are valuable tools for high-throughput identification of novel host ligand-binding proteins that have the potential to play key roles in the virulence mechanisms of pathogens.",,"['Pinne, Marija', 'Matsunaga, James', 'Haake, David A.']",,,,
,PMC,Nearly Constant Shedding of Diverse Enteric Viruses by Two Healthy Infants,http://dx.doi.org/10.1128/JCM.01589-12,PMC3486243,,,"Stool samples from two healthy infant siblings collected at about weekly intervals during their first year of life were analyzed by PCR for 15 different enteric viral genera. Adenovirus, Aichi virus, Anellovirus, Astrovirus, Bocavirus, Enterovirus, Parechovirus, Picobirnavirus, and Rotavirus were detected. Not detected were Coronavirus, Cardiovirus, Cosavirus, Salivirus, Sapovirus, and Norovirus. Long-term virus shedding, lasting from one to 12 months, was observed for adenoviruses, anelloviruses, bocaviruses, enteroviruses, parechoviruses, and picobirnaviruses. Repeated administration of oral poliovirus vaccine resulted in progressively shorter periods of poliovirus detection. Four nonpolio enterovirus genotypes were also detected. An average of 1.8 distinct human viruses were found per time point. Ninety-two percent (66/72) of the fecal samples tested contained one to five different human viruses. Two British siblings in the mid-1980s showed nearly constant fecal viral shedding. Our results demonstrate that frequent enteric infections with diverse viruses occur during early childhood in the absence of severe clinical symptoms.",,"['Kapusinszky, Beatrix', 'Minor, Philip', 'Delwart, Eric']",,,,
,PMC,Comparison of the GenMark Diagnostics eSensor Respiratory Viral Panel to Real-Time PCR for Detection of Respiratory Viruses in Children,http://dx.doi.org/10.1128/JCM.01384-12,PMC3486226,,,"A novel eSensor respiratory viral panel (eSensor RVP) multiplexed nucleic acid amplification test (GenMark Diagnostics, Inc., Carlsbad, CA) was compared to laboratory-developed real-time PCR assays for the detection of various respiratory viruses. A total of 250 frozen archived pediatric respiratory specimens previously characterized as either negative or positive for one or more viruses by real-time PCR were examined using the eSensor RVP. Overall agreement between the eSensor RVP and corresponding real-time PCR assays for shared analytes was 99.2% (kappa = 0.96 [95% confidence interval {CI}, 0.94 to 0.98]). The combined positive percent agreement was 95.4% (95% CI, 92.5 to 97.3); the negative percent agreement was 99.7% (95% CI, 99.4 to 99.8). The mean real-time PCR threshold cycle (C(T)) value for specimens with discordant results was 39.73 (95% CI, 38.03 to 41.43). Detection of coinfections and correct identification of influenza A virus subtypes were comparable between methods. Of note, the eSensor RVP rhinovirus assay was found to be more sensitive and specific than the corresponding rhinovirus real-time PCR. In contrast, the eSensor RVP adenovirus B, C, and E assays demonstrated some cross-reactivity when tested against known adenovirus serotypes representing groups A through F. The eSensor RVP is robust and relatively easy to perform, it involves a unique biosensor technology for target detection, and its multiplexed design allows for efficient and simultaneous interrogation of a single specimen for multiple viruses. Potential drawbacks include a slower turnaround time and the need to manipulate amplified product during the protocol, increasing the possibility of contamination.",,"['Pierce, Virginia M.', 'Hodinka, Richard L.']",,,,
,PMC,"Genomic analysis of 16 Colorado human NL63 coronaviruses identifies a new genotype, high sequence diversity in the N-terminal domain of the spike gene and evidence of recombination",http://dx.doi.org/10.1099/vir.0.044628-0,PMC4091283,,,"This study compared the complete genome sequences of 16 NL63 strain human coronaviruses (hCoVs) from respiratory specimens of paediatric patients with respiratory disease in Colorado, USA, and characterized the epidemiology and clinical characteristics associated with circulating NL63 viruses over a 3-year period. From 1 January 2009 to 31 December 2011, 92 of 9380 respiratory specimens were found to be positive for NL63 RNA by PCR, an overall prevalence of 1 %. NL63 viruses were circulating during all 3 years, but there was considerable yearly variation in prevalence and the month of peak incidence. Phylogenetic analysis comparing the genome sequences of the 16 Colorado NL63 viruses with those of the prototypical hCoV-NL63 and three other NL63 viruses from the Netherlands demonstrated that there were three genotypes (A, B and C) circulating in Colorado from 2005 to 2010, and evidence of recombination between virus strains was found. Genotypes B and C co-circulated in Colorado in 2005, 2009 and 2010, but genotype A circulated only in 2005 when it was the predominant NL63 strain. Genotype C represents a new lineage that has not been described previously. The greatest variability in the NL63 virus genomes was found in the N-terminal domain (NTD) of the spike gene (nt 1–600, aa 1–200). Ten different amino acid sequences were found in the NTD of the spike protein among these NL63 strains and the 75 partial published sequences of NTDs from strains found at different times throughout the world.",,"['Dominguez, Samuel R.', 'Sims, Gregory E.', 'Wentworth, David E.', 'Halpin, Rebecca A.', 'Robinson, Christine C.', 'Town, Christopher D.', 'Holmes, Kathryn V.']",,,,
,PMC,Comparison of the Etiology of Viral Respiratory Illnesses in Inner-City and Suburban Infants,http://dx.doi.org/10.1093/infdis/jis504,PMC3466995,,,"Background. The risk of developing childhood asthma has been linked to the severity and etiology of viral respiratory illnesses in early childhood. Since inner-city infants have unique environmental exposures, we hypothesized that patterns of respiratory viral infections would also be distinct. Methods. We compared the viral etiology of respiratory illnesses in 2 groups: a cohort of 515 infants from 4 inner-city areas and a cohort of 285 infants from mainly suburban Madison, Wisconsin. Nasal secretions were sampled during periods of respiratory illness and at 1 year of age and were analyzed for viral pathogens by multiplex polymerase chain reaction. Results. Overall, inner-city infants had lower rates of viral detection. Considering specific viruses, sick urban infants had lower rates of detectable rhinovirus or respiratory syncytial virus infection and higher rates of adenovirus infection. Every urban site had a higher proportion of adenovirus-positive samples associated with illnesses (10%–21%), compared with Madison (6%). Conclusions. These findings provide evidence that inner-city babies have different patterns of viral respiratory illnesses than babies who grow up in a more suburban location. These findings raise important questions about the etiology of virus-negative illnesses in urban infants and the possibility of long-term consequences of early life infections with adenovirus in this population.",,"['Gern, James E.', 'Pappas, Tressa', 'Visness, Cynthia M.', 'Jaffee, Katy F.', 'Lemanske, Robert F.', 'Togias, Alkis', 'Bloomberg, Gordon R.', 'Cruikshank, William W.', 'Lamm, Carin', 'Tuzova, Marina', 'Wood, Robert A.', 'Lee, Wai Ming']",,,,
,PMC,Immune Heterogeneity in Neuroinflammation: Dendritic Cells in the Brain,http://dx.doi.org/10.1007/s11481-012-9414-8,PMC4279719,,,"Dendritic cells (DC) are critical to an integrated immune response and serve as the key link between the innate and adaptive arms of the immune system. Under steady state conditions, brain DC’s act as sentinels, continually sampling their local environment. They share this function with macrophages derived from the same basic hemopoietic (bone marrow-derived) precursor and with parenchymal microglia that arise from a unique non-hemopoietic origin. While multiple cells may serve as antigen presenting cells (APCs), dendritic cells present both foreign and self-proteins to naïve T cells that, in turn, carry out effector functions that serve to protect or destroy. The resulting activation of the adaptive response is a critical step to resolution of injury or infection and is key to survival. In this review we will explore the critical roles that DCs play in the brain’s response to neuroinflammatory disease with emphasis on how the brain’s microenvironment impacts these actions.",,"Colton, Carol A.",,,,
,PMC,Epitope Mapping of Broadly Neutralizing HIV-2 Human Monoclonal Antibodies,http://dx.doi.org/10.1128/JVI.01632-12,PMC3486499,,,"Recent studies have shown that natural infection by HIV-2 leads to the elicitation of high titers of broadly neutralizing antibodies (NAbs) against primary HIV-2 strains (T. I. de Silva, et al., J. Virol. 86:930–946, 2012; R. Kong, et al., J. Virol. 86:947–960, 2012; G. Ozkaya Sahin, et al., J. Virol. 86:961–971, 2012). Here, we describe the envelope (Env) binding and neutralization properties of 15 anti-HIV-2 human monoclonal antibodies (MAbs), 14 of which were newly generated from 9 chronically infected subjects. All 15 MAbs bound specifically to HIV-2 gp120 monomers and neutralized heterologous primary virus strains HIV-2(7312A) and HIV-2(ST). Ten of 15 MAbs neutralized a third heterologous primary virus strain, HIV-2(UC1). The median 50% inhibitory concentrations (IC(50)s) for these MAbs were surprisingly low, ranging from 0.007 to 0.028 μg/ml. Competitive Env binding studies revealed three MAb competition groups: CG-I, CG-II, and CG-III. Using peptide scanning, site-directed mutagenesis, chimeric Env constructions, and single-cycle virus neutralization assays, we mapped the epitope of CG-I antibodies to a linear region in variable loop 3 (V3), the epitope of CG-II antibodies to a conformational region centered on the carboxy terminus of V4, and the epitope(s) of CG-III antibodies to conformational regions associated with CD4- and coreceptor-binding sites. HIV-2 Env is thus highly immunogenic in vivo and elicits antibodies having diverse epitope specificities, high potency, and wide breadth. In contrast to the HIV-1 Env trimer, which is generally well shielded from antibody binding and neutralization, HIV-2 is surprisingly vulnerable to broadly reactive NAbs. The availability of 15 human MAbs targeting diverse HIV-2 Env epitopes can facilitate comparative studies of HIV/SIV Env structure, function, antigenicity, and immunogenicity.",,"['Kong, Rui', 'Li, Hui', 'Georgiev, Ivelin', 'Changela, Anita', 'Bibollet-Ruche, Frederic', 'Decker, Julie M.', 'Rowland-Jones, Sarah L.', 'Jaye, Assan', 'Guan, Yongjun', 'Lewis, George K.', 'Langedijk, Johannes P. M.', 'Hahn, Beatrice H.', 'Kwong, Peter D.', 'Robinson, James E.', 'Shaw, George M.']",,,,
,PMC,Complete Genome Sequence of a Variant Porcine Epidemic Diarrhea Virus Strain Isolated in China,http://dx.doi.org/10.1128/JVI.02228-12,PMC3486467,,,"Since October 2010, an outbreak of porcine epidemic diarrhea (PED) has been observed in some provinces of China. Here we report the complete genome sequence of porcine epidemic diarrhea virus (PEDV) strain LC, which was recently isolated from sucking piglets that suffered from severe watery diarrhea in Guangdong. It will help in understanding the epidemiological and molecular characteristics of PEDV in China.",,"['Chen, Feng', 'Pan, Yongfei', 'Zhang, Xiangbin', 'Tian, Xiaoyan', 'Wang, Dongdong', 'Zhou, Qingfeng', 'Song, Yanhua', 'Bi, Yingzuo']",,,,
,PMC,p33-Independent Activation of a Truncated p92 RNA-Dependent RNA Polymerase of Tomato Bushy Stunt Virus in Yeast Cell-Free Extract,http://dx.doi.org/10.1128/JVI.01303-12,PMC3486448,,,"Plus-stranded RNA viruses replicate in membrane-bound structures containing the viral replicase complex (VRC). A key component of the VRC is the virally encoded RNA-dependent RNA polymerase (RdRp), which should be activated and incorporated into the VRC after its translation. To study the activation of the RdRp of Tomato bushy stunt virus (TBSV), a small tombusvirus of plants, we used N-terminal truncated recombinant RdRp, which supported RNA synthesis in a cell-free yeast extract-based assay. The truncated RdRp required a cis-acting RNA replication element and soluble host factors, while unlike the full-length TBSV RdRp, the truncated RdRp did not need the viral p33 replication cofactor or cellular membranes for RNA synthesis. Interestingly, the truncated RdRp used 3′-terminal extension for initiation and terminated prematurely at an internal cis-acting element. However, the truncated RdRp could perform de novo initiation on a TBSV plus-strand RNA template in the presence of the p33 replication cofactor, cellular membranes, and soluble host proteins. Altogether, the data obtained with the truncated RdRp indicate that this RdRp still requires activation, but with the participation of fewer components than with the full-length RdRp, making it suitable for future studies on dissection of the RdRp activation mechanism.",,"['Pogany, Judit', 'Nagy, Peter D.']",,,,
,PMC,"Complete Genome of Transmissible Gastroenteritis Virus AYU Strain Isolated in Shanghai, China",http://dx.doi.org/10.1128/JVI.01839-12,PMC3486336,,,"Transmissible gastroenteritis virus strain AYU was isolated in Shanghai. The complete genome has a length of 28,582 bp and contains seven open reading frames. Sequence analysis suggested that Shanghai strain AYU and U.S. strain Purdue P115 are derived from a common ancestor, as they have 99.6% similarity at the nucleotide level.",,"['Hou, Yixuan', 'Yue, Xiuwei', 'Cai, Xuehui', 'Wang, Shujie', 'Liu, Yonggang', 'Yuan, Congli', 'Cui, Li', 'Hua, Xiuguo', 'Yang, Zhibiao']",,,,
,PMC,Inclusion Bodies Are a Site of Ebolavirus Replication,http://dx.doi.org/10.1128/JVI.01525-12,PMC3486333,,,"Inclusion bodies are a characteristic feature of ebolavirus infections in cells. They contain large numbers of preformed nucleocapsids, but their biological significance has been debated, and they have been suggested to be aggregates of viral proteins without any further biological function. However, recent data for other viruses that produce similar structures have suggested that inclusion bodies might be involved in genome replication and transcription. In order to study filovirus inclusion bodies, we fused mCherry to the ebolavirus polymerase L, which is found in inclusion bodies. The resulting L-mCherry fusion protein was functional in minigenome assays and incorporated into virus-like particles. Importantly, L-mCherry fluorescence in transfected cells was readily detectable and distributed in a punctate pattern characteristic for inclusion bodies. A recombinant ebolavirus encoding L-mCherry instead of L was rescued and showed virtually identical growth kinetics and endpoint titers to those for wild-type virus. Using this virus, we showed that the onset of inclusion body formation corresponds to the onset of viral genome replication, but that viral transcription occurs prior to inclusion body formation. Live-cell imaging further showed that inclusion bodies are highly dynamic structures and that they can undergo dramatic reorganization during cell division. Finally, by labeling nascent RNAs using click technology we showed that inclusion bodies are indeed the site of viral RNA synthesis. Based on these data we conclude that, rather than being inert aggregates of nucleocapsids, ebolavirus inclusion bodies are in fact complex and dynamic structures and an important site at which viral RNA replication takes place.",,"['Hoenen, Thomas', 'Shabman, Reed S.', 'Groseth, Allison', 'Herwig, Astrid', 'Weber, Michaela', 'Schudt, Gordian', 'Dolnik, Olga', 'Basler, Christopher F.', 'Becker, Stephan', 'Feldmann, Heinz']",,,,
,PMC,Modulation of Ribosomal Frameshifting Frequency and Its Effect on the Replication of Rous Sarcoma Virus,http://dx.doi.org/10.1128/JVI.01846-12,PMC3486330,,,"Programmed −1 ribosomal frameshifting is widely used in the expression of RNA virus replicases and represents a potential target for antiviral intervention. There is interest in determining the extent to which frameshifting efficiency can be modulated before virus replication is compromised, and we have addressed this question using the alpharetrovirus Rous sarcoma virus (RSV) as a model system. In RSV, frameshifting is essential in the production of the Gag-Pol polyprotein from the overlapping gag and pol coding sequences. The frameshift signal is composed of two elements, a heptanucleotide slippery sequence and, just downstream, a stimulatory RNA structure that has been proposed to be an RNA pseudoknot. Point mutations were introduced into the frameshift signal of an infectious RSV clone, and virus replication was monitored following transfection and subsequent infection of susceptible cells. The introduced mutations were designed to generate a range of frameshifting efficiencies, yet with minimal impact on encoded amino acids. Our results reveal that point mutations leading to a 3-fold decrease in frameshifting efficiency noticeably reduce virus replication and that further reduction is severely inhibitory. In contrast, a 3-fold stimulation of frameshifting is well tolerated. These observations suggest that small-molecule inhibitors of frameshifting are likely to have potential as agents for antiviral intervention. During the course of this work, we were able to confirm, for the first time in vivo, that the RSV stimulatory RNA is indeed an RNA pseudoknot but that the pseudoknot per se is not absolutely required for virus viability.",,"['Nikolić, Emily I. C.', 'King, Louise M.', 'Vidakovic, Marijana', 'Irigoyen, Nerea', 'Brierley, Ian']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.02429-12,PMC3486328,,,,,,,,,
,PMC,Monitoring of S Protein Maturation in the Endoplasmic Reticulum by Calnexin Is Important for the Infectivity of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.01250-12,PMC3486308,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS, a fatal pulmonary disorder with no effective treatment. We found that SARS-CoV spike glycoprotein (S protein), a key molecule for viral entry, binds to calnexin, a molecular chaperone in the endoplasmic reticulum (ER), but not to calreticulin, a homolog of calnexin. Calnexin bound to most truncated mutants of S protein, and S protein bound to all mutants of calnexin. Pseudotyped virus carrying S protein (S-pseudovirus) produced by human cells that were treated with small interfering RNA (siRNA) for calnexin expression (calnexin siRNA-treated cells) showed significantly lower infectivity than S-pseudoviruses produced by untreated and control siRNA-treated cells. S-pseudovirus produced by calnexin siRNA-treated cells contained S protein modified with N-glycan side chains differently from other two S proteins and consisted of two kinds of viral particles: those of normal density with little S protein and those of high density with abundant S protein. Treatment with peptide-N-glycosidase F (PNGase F), which removes all types of N-glycan side chains from glycoproteins, eliminated the infectivity of S-pseudovirus. S-pseudovirus and SARS-CoV produced in the presence of α-glucosidase inhibitors, which disrupt the interaction between calnexin and its substrates, showed significantly lower infectivity than each virus produced in the absence of those compounds. In S-pseudovirus, the incorporation of S protein into viral particles was obviously inhibited. In SARS-CoV, viral production was obviously inhibited. These findings demonstrated that calnexin strictly monitors the maturation of S protein by its direct binding, resulting in conferring infectivity on SARS-CoV.",,"['Fukushi, Masaya', 'Yoshinaka, Yoshiyuki', 'Matsuoka, Yusuke', 'Hatakeyama, Seisuke', 'Ishizaka, Yukihito', 'Kirikae, Teruo', 'Sasazuki, Takehiko', 'Miyoshi-Akiyama, Tohru']",,,,
,PMC,Evaluation of Phosphatidylinositol-4-Kinase IIIα as a Hepatitis C Virus Drug Target,http://dx.doi.org/10.1128/JVI.01320-12,PMC3486294,,,"Phosphatidylinositol-4-kinase IIIα (PI4KIIIα) is an essential host cell factor for hepatitis C virus (HCV) replication. An N-terminally truncated 130-kDa form was used to reconstitute an in vitro biochemical lipid kinase assay that was optimized for small-molecule compound screening and identified potent and specific inhibitors. Cell culture studies with PI4KIIIα inhibitors demonstrated that the kinase activity was essential for HCV RNA replication. Two PI4KIIIα inhibitors were used to select cell lines harboring HCV replicon mutants with a 20-fold loss in sensitivity to the compounds. Reverse genetic mapping isolated an NS4B-NS5A segment that rescued HCV RNA replication in PIK4IIIα-deficient cells. HCV RNA replication occurs on specialized membranous webs, and this study with PIK4IIIα inhibitor-resistant mutants provides a genetic link between NS4B/NS5A functions and PI4-phosphate lipid metabolism. A comprehensive assessment of PI4KIIIα as a drug target included its evaluation for pharmacologic intervention in vivo through conditional transgenic murine lines that mimic target-specific inhibition in adult mice. Homozygotes that induce a knockout of the kinase domain or knock in a single amino acid substitution, kinase-defective PI4KIIIα, displayed a lethal phenotype with a fairly widespread mucosal epithelial degeneration of the gastrointestinal tract. This essential host physiologic role raises doubt about the pursuit of PI4KIIIα inhibitors for treatment of chronic HCV infection.",,"['Vaillancourt, Frédéric H.', 'Brault, Martine', 'Pilote, Louise', 'Uyttersprot, Nathalie', 'Gaillard, Elias T.', 'Stoltz, James H.', 'Knight, Brian L.', 'Pantages, Lynn', 'McFarland, Mary', 'Breitfelder, Steffen', 'Chiu, Tim T.', 'Mahrouche, Louiza', 'Faucher, Anne-Marie', 'Cartier, Mireille', 'Cordingley, Michael G.', 'Bethell, Richard C.', 'Jiang, Huiping', 'White, Peter W.', 'Kukolj, George']",,,,
,PMC,"Broad-Spectrum Antivirals against 3C or 3C-Like Proteases of Picornaviruses, Noroviruses, and Coronaviruses",http://dx.doi.org/10.1128/JVI.01348-12,PMC3486288,,,"Phylogenetic analysis has demonstrated that some positive-sense RNA viruses can be classified into the picornavirus-like supercluster, which includes picornaviruses, caliciviruses, and coronaviruses. These viruses possess 3C or 3C-like proteases (3Cpro or 3CLpro, respectively), which contain a typical chymotrypsin-like fold and a catalytic triad (or dyad) with a Cys residue as a nucleophile. The conserved key sites of 3Cpro or 3CLpro may serve as attractive targets for the design of broad-spectrum antivirals for multiple viruses in the supercluster. We previously reported the structure-based design and synthesis of potent protease inhibitors of Norwalk virus (NV), a member of the Caliciviridae family. We report herein the broad-spectrum antiviral activities of three compounds possessing a common dipeptidyl residue with different warheads, i.e., an aldehyde (GC373), a bisulfite adduct (GC376), and an α-ketoamide (GC375), against viruses that belong to the supercluster. All compounds were highly effective against the majority of tested viruses, with half-maximal inhibitory concentrations in the high nanomolar or low micromolar range in enzyme- and/or cell-based assays and with high therapeutic indices. We also report the high-resolution X-ray cocrystal structures of NV 3CLpro-, poliovirus 3Cpro-, and transmissible gastroenteritis virus 3CLpro- GC376 inhibitor complexes, which show the compound covalently bound to a nucleophilic Cys residue in the catalytic site of the corresponding protease. We conclude that these compounds have the potential to be developed as antiviral therapeutics aimed at a single virus or multiple viruses in the picornavirus-like supercluster by targeting 3Cpro or 3CLpro.",,"['Kim, Yunjeong', 'Lovell, Scott', 'Tiew, Kok-Chuan', 'Mandadapu, Sivakoteswara Rao', 'Alliston, Kevin R.', 'Battaile, Kevin P.', 'Groutas, William C.', 'Chang, Kyeong-Ok']",,,,
,PMC,Flavivirus Replication Complex Assembly Revealed by DNAJC14 Functional Mapping,http://dx.doi.org/10.1128/JVI.01022-12,PMC3486285,,,"DNAJC14 is an Hsp40 family member that broadly modulates flavivirus replication. The mechanism by which DNAJC14 stoichiometrically participates in flavivirus replication complex (RC) formation is unknown; both reduced and elevated levels result in replication inhibition. Using yellow fever virus (YFV), we demonstrate that DNAJC14 redistributes and clusters with YFV nonstructural proteins via a transmembrane domain and a newly identified membrane-binding domain (MBD), which both mediate targeting to detergent-resistant membranes. Furthermore, the RC and DNAJC14 reside as part of a protein interaction network that remains after 1% Triton solubilization. Mutagenesis studies demonstrate that entry into this protein interaction network requires the DNAJC14 C-terminal self-interaction domain. Fusion of the DNAJC14 MBD and self-interaction domain with another Hsp40 family protein is sufficient to confer YFV-inhibitory activity. Our findings support a novel model of DNAJC14 action that includes specific membrane targeting of both DNAJC14 and YFV replication proteins, the formation of protein interactions, and a microdomain-specific chaperone event leading to RC formation. This process alters the properties of the RC membrane and results in the formation of a protein scaffold that maintains the RC.",,"['Yi, Zhigang', 'Yuan, Zhenghong', 'Rice, Charles M.', 'MacDonald, Margaret R.']",,,,
,PMC,"Recent Transmission of a Novel Alphacoronavirus, Bat Coronavirus HKU10, from Leschenault's Rousettes to Pomona Leaf-Nosed Bats: First Evidence of Interspecies Transmission of Coronavirus between Bats of Different Suborders",http://dx.doi.org/10.1128/JVI.01305-12,PMC3486284,,,"Although coronaviruses are known to infect various animals by adapting to new hosts, interspecies transmission events are still poorly understood. During a surveillance study from 2005 to 2010, a novel alphacoronavirus, BatCoV HKU10, was detected in two very different bat species, Ro-BatCoV HKU10 in Leschenault's rousettes (Rousettus leschenaulti) (fruit bats in the suborder Megachiroptera) in Guangdong and Hi-BatCoV HKU10 in Pomona leaf-nosed bats (Hipposideros pomona) (insectivorous bats in the suborder Microchiroptera) in Hong Kong. Although infected bats appeared to be healthy, Pomona leaf-nosed bats carrying Hi-BatCoV HKU10 had lower body weights than uninfected bats. To investigate possible interspecies transmission between the two bat species, the complete genomes of two Ro-BatCoV HKU10 and six Hi-BatCoV HKU10 strains were sequenced. Genome and phylogenetic analyses showed that Ro-BatCoV HKU10 and Hi-BatCoV HKU10 represented a novel alphacoronavirus species, sharing highly similar genomes except in the genes encoding spike proteins, which had only 60.5% amino acid identities. Evolution of the spike protein was also rapid in Hi-BatCoV HKU10 strains from 2005 to 2006 but stabilized thereafter. Molecular-clock analysis dated the most recent common ancestor of all BatCoV HKU10 strains to 1959 (highest posterior density regions at 95% [HPDs], 1886 to 2002) and that of Hi-BatCoV HKU10 to 1986 (HPDs, 1956 to 2004). The data suggested recent interspecies transmission from Leschenault's rousettes to Pomona leaf-nosed bats in southern China. Notably, the rapid adaptive genetic change in BatCoV HKU10 spike protein by ∼40% amino acid divergence after recent interspecies transmission was even greater than the ∼20% amino acid divergence between spike proteins of severe acute respiratory syndrome-related Rhinolophus bat coronavirus (SARSr-CoV) in bats and civets. This study provided the first evidence for interspecies transmission of coronavirus between bats of different suborders.",,"['Lau, Susanna K. P.', 'Li, Kenneth S. M.', 'Tsang, Alan K. L.', 'Shek, Chung-Tong', 'Wang, Ming', 'Choi, Garnet K. Y.', 'Guo, Rongtong', 'Wong, Beatrice H. L.', 'Poon, Rosana W. S.', 'Lam, Carol S. F.', 'Wang, Sylvia Y. H.', 'Fan, Rachel Y. Y.', 'Chan, Kwok-Hung', 'Zheng, Bo-Jian', 'Woo, Patrick C. Y.', 'Yuen, Kwok-Yung']",,,,
,PMC,Broadly Neutralizing Immune Responses against Hepatitis C Virus Induced by Vectored Measles Viruses and a Recombinant Envelope Protein Booster,http://dx.doi.org/10.1128/JVI.01776-12,PMC3486281,,,"Hepatitis C virus (HCV) infection remains a serious public health problem worldwide. Treatments are limited, and no preventive vaccine is available. Toward developing an HCV vaccine, we engineered two recombinant measles viruses (MVs) expressing structural proteins from the prototypic HCV subtype 1a strain H77. One virus directs the synthesis of the HCV capsid (C) protein and envelope glycoproteins (E1 and E2), which fold properly and form a heterodimer. The other virus expresses the E1 and E2 glycoproteins separately, with each one fused to the cytoplasmic tail of the MV fusion protein. Although these hybrid glycoproteins were transported to the plasma membrane, they were not incorporated into MV particles. Immunization of MV-susceptible, genetically modified mice with either vector induced neutralizing antibodies to MV and HCV. A boost with soluble E2 protein enhanced titers of neutralizing antibody against the homologous HCV envelope. In animals primed with MV expressing properly folded HCV C-E1-E2, boosting also induced cross-neutralizating antibodies against two heterologous HCV strains. These results show that recombinant MVs retain the ability to induce MV-specific humoral immunity while also eliciting HCV neutralizing antibodies, and that anti-HCV immunity can be boosted with a single dose of purified E2 protein. The use of MV vectors could have advantages for pediatric HCV vaccination.",,"['Reyes-del Valle, Jorge', 'de la Fuente, Cynthia', 'Turner, Mallory A.', 'Springfeld, Christoph', 'Apte-Sengupta, Swapna', 'Frenzke, Marie E.', 'Forest, Amelie', 'Whidby, Jillian', 'Marcotrigiano, Joseph', 'Rice, Charles M.', 'Cattaneo, Roberto']",,,,
,PMC,Intranasal Treatment with Poly(I·C) Protects Aged Mice from Lethal Respiratory Virus Infections,http://dx.doi.org/10.1128/JVI.01410-12,PMC3486278,,,"In the 2002-2003 severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic, no patients under 24 years of age died, while mortality was greater than 50% in those over 65 years. Greater than 90% of all deaths from influenza A virus (IAV) occur in the elderly (>65 years of age). To address this age-related susceptibility to SARS-CoV and IAV, we infected C57BL/6 (B6) mice with mouse-adapted SARS-CoV (MA15) or IAV (PR8), both of which cause severe disease in aged mice. Intranasal pretreatment of aged mice with poly(I·C) (a TLR3 agonist) and, to a lesser extent, CpG, R848, or lipopolysaccharide (TLR9, TLR7/8, or TLR4 agonists), provided a high level of protection [90% to 100% survival rate after poly(I·C) treatment] against lethal MA15 or IAV challenge and reduced pathological changes and virus loads in the lungs at early times after infection. Poly(I·C) pretreatment upregulated beta interferon (IFN-β), IFN-γ, IL-1β, and tumor necrosis factor (TNF) gene expression in the lungs. Intranasal pretreatment with IFN-β or IFN-γ but not IL-1β or TNF also protected aged mice, consistent with the notion that poly(I·C) pretreatment functioned, at least in part, by inducing IFN-β and IFN-γ. We also identified a potential cellular target for poly(I·C) by showing that treatment inhibited virus replication in primary human airway epithelial cells. These results suggest that intranasal poly(I·C) should be evaluated as a prophylactic agent in aged individuals at high risk for contracting SARS-CoV or IAV infections.",,"['Zhao, Jincun', 'Wohlford-Lenane, Christine', 'Zhao, Jingxian', 'Fleming, Erica', 'Lane, Thomas E.', 'McCray, Paul B.', 'Perlman, Stanley']",,,,
,PMC,Etiology and Seasonality of Viral Respiratory Infections in Rural Honduran Children,http://dx.doi.org/10.1097/INF.0b013e31826052eb,PMC3473163,,,"BACKGROUND: Limited data are available in Honduras describing the etiology and seasonality of respiratory infections, especially in rural outpatient settings. Better data may lead to improved therapeutic and preventative strategies. The goal of our study was to determine the viral etiology and seasonality of acute respiratory infections in a rural Honduran population of children. METHODS: Prospective clinic surveillance was conducted to identify children <5 years of age presenting with respiratory symptoms <5 days duration. We obtained data on age, sex, medical history, breastfeeding history, symptoms, risk factors, house hold setting, temperature, respiratory rate, and chest exam findings. To assess the association between specific viruses and weather, regional meteorological data were collected. Nasopharyngeal samples were tested for 16 respiratory viruses using a multiplex PCR panel. RESULTS: From February 2010 through June 2011, 345 children <5 years of age were enrolled; 17%, 23%, 30%, and 31% were <6, 6–11, 12–23, and 24–60 months old, respectively. Including all clinics in the region, 44.5% of patients <5 years of age with documented respiratory diagnoses were enrolled. At least one virus was identified in 75.4% children, of which 7.5% were co-infections; 13.3% were positive for parainfluenza, 11.9% for influenza, 8.1% for human metapneumovirus (hMPV), and 7.5% for respiratory syncytial virus (RSV). Rainfall correlated with parainfluenza (p≤0.0001), influenza (p≤0.0001), hMPV (p= 0.0182), and RSV (p≤0.0001). CONCLUSIONS: These results suggest that the spectrum of viruses in ill rural Honduran children is similar to that in North and Central America, though the seasonality is typical of some tropical regions.",,"['Schlaudecker, Elizabeth P.', 'Heck, Joan P.', 'MacIntyre, Elizabeth T.', 'Martinez, Ruben', 'Dodd, Caitlin N.', 'McNeal, Monica M.', 'Staat, Mary A.', 'Heck, Jeffery E.', 'Steinhoff, Mark C.']",,,,
,PMC,Effect of the 2009 Influenza A/H1N1 Pandemic on Viral Respiratory Infections in the First Year of Life,http://dx.doi.org/10.1097/INF.0b013e31825f29db,PMC3462885,,,"BACKGROUND: Effect of the 2009 H1N1 influenza pandemic on viral epidemiology of upper and lower respiratory tract infections (URI and LRI) in healthy infants in the first year of life has not been well studied. METHODS: A total of 180 healthy infants were enrolled from birth and monitored for occurrences of URI and its LRI and acute otitis media (AOM) complications until the first AOM episode or between 6 and 12 months of age. Nasopharyngeal specimens collected during acute respiratory illnesses were tested for 18 viruses. RESULTS: Between October 2008 and April 2011, 373 URI episodes, including 20 with LRI, in 139 infants were documented. Viral studies were performed on 189 URI episodes; 87% were positive. Throughout the 31-month period (1386 patient-months), rhinovirus was the predominant virus causing URI (55%); RSV was the major cause of LRI (64%). While there was a significant increase in parent-initiated visit rate during the 15-month influenza pandemic as compared with pre- and post- pandemic periods, only 4 cases of influenza were detected (2 cases during and 2 cases pre- and post- pandemic). CONCLUSION: The 2009 influenza A/H1N1 pandemic had no impact on the overall viral epidemiology of respiratory infections in healthy infants in the first year of life but resulted in increased parent-initiated visits due to respiratory symptoms. Maternal antibody and absence of co-morbidity may explain the low influenza burden while parental anxiety may explain the increased healthcare visit rate during the pandemic.",,"['Ede, Linda C.', 'Loeffelholz, Michael J.', 'Alvarez-Fernandez, Pedro', 'Pong, Dan L.', 'Patel, Janak A.', 'McCormick, David P.', 'Chonmaitree, Tasnee']",,,,
,PMC,MHC mismatch results in neural progenitor cell rejection following spinal cord transplantation in a model of viral-induced demyelination,http://dx.doi.org/10.1002/stem.1234,PMC3479361,,,"Transplantation of syngeneic neural progenitor cells (NPCs) into mice persistently infected with the JHM strain of mouse hepatitis virus (JHMV) results in enhanced differentiation into oligodendrocyte progenitor cells (OPCs) that is associated with remyelination, axonal sparing, and clinical improvement. Whether allogeneic NPCs are tolerated or induce immune-mediated rejection is controversial and poorly defined under neuroinflammatory demyelinating conditions. We have used the JHMV-induced demyelination model to evaluate the antigenicity of transplanted allogeneic NPCs within the central nervous system (CNS) of mice with established immune-mediated demyelination. Cultured NPCs constitutively expressed the co-stimulatory molecules CD80/CD86 and IFN-γ treatment induced expression of MHC class I and II antigens. Injection of allogeneic C57BL/6 NPCs (H-2(b) background) led to a delayed type hypersensitivity (DTH) response in Balb/c (H-2(d) background) associated with T cell proliferation and IFN-γ secretion following co-culture with allogeneic NPCs. Transplantation of MHC-mismatched NPCs into JHMV-infected mice resulted in increased transcripts encoding the T cell chemoattractant chemokines CXCL9 and CXCL10 that correlated with increased T cell infiltration that was associated with NPC rejection. Treatment of MHC-mismatched mice with T cell subset-specific depleting antibodies increased survival of allogeneic NPCs without affecting commitment to an oligodendroyte lineage. Collectively, these results show that allogeneic NPCs are antigenic and T cells contribute to rejection following transplantation into an inflamed CNS suggesting that immunomodulatory treatments may be necessary to prolong survival of allogeneic cells.",,"['Weinger, Jason G.', 'Weist, Brian M.', 'Plaisted, Warren C.', 'Klaus, Suzi M.', 'Walsh, Craig M.', 'Lane, Thomas E.']",,,,
,PMC,Autophagy As A Stress Response And Quality Control Mechanism—Implications for Cell Injury and Human Disease,http://dx.doi.org/10.1146/annurev-pathol-020712-163918,PMC3971121,,,"Autophagy, a vital catabolic process that degrades cytoplasmic components within the lysosome, serves as an essential cytoprotective response to pathologic stresses that occur during diseases such as cancer, ischemia, and infection. In addition to its role as a stress response pathway, autophagy plays an essential quality control function in the cell by promoting basal turnover of long-lived proteins and organelles as well as selectively degrading damaged cellular components. This homeostatic function protects against a wide variety of diseases including neurodegeneration, myopathy, liver disease, and diabetes. This review discusses our current understanding of these two principal functions for autophagy as a physiologic stress response and quality control mechanism within mammalian cells and details how alterations in autophagy promote human disease.",,"['Murrow, Lyndsay', 'Debnath, Jayanta']",,,,
,PMC,Role of Coatomer Protein I in Virus Replication,http://dx.doi.org/10.4172/2324-8955.1000102,PMC3879076,,,"Coatomer protein I (COPI) is well known as the protein coat surrounding vesicles involved in returning endoplasmic reticulum (ER)-resident proteins to the ER. COPI coats are also found in vesicles involved in other trafficking processes including endocytosis, autophagy and anterograde transport in the secretory pathway. In view of the diverse functions of COPI proteins, it is expected that they will affect virus replication, and many reports of such COPI involvement have now appeared. The experimental approaches most often employ specific siRNA to deplete COPI subunits or brefeldin A to block COPI activation. Here we briefly describe the results obtained with viruses in which COPI is found to have a role in replication. The results demonstrate that COPI affects viruses quite differently with effects observed in processes such as entry, RNA replication, and intracellular transport of viral proteins.",,"['Thompson, Jennifer A.', 'Brown, Jay C.']",,,,
,PMC,A unique host defense pathway: TRIF mediates both antiviral and antibacterial immune responses,http://dx.doi.org/10.1016/j.micinf.2012.10.011,PMC3537922,,,"Both anti-viral and anti-bacterial host defense mechanisms involve TRIF signaling. TRIF provides early clearance of pathogens and coordination of a local inflammatory ensemble through an interferon cascade, while it may trigger organ damage. The multipotentiality of TRIF-mediated immune machinery may direct the fate of our continuous battle with microbes.",,"['Hyun, Jinhee', 'Kanagavelu, Saravana', 'Fukata, Masayuki']",,,,
,PMC,Epstein-Barr virus-induced gene 3 negatively regulates neuroinflammation and T cell activation following coronavirus-induced encephalomyelitis,http://dx.doi.org/10.1016/j.jneuroim.2012.10.005,PMC3534940,,,"Epstein-Barr virus-induced gene 3 (EBI3) associates with p28 and p35 to form the immunomodulatory cytokines IL-27 and IL-35, respectively. Infection of EBI3−/− mice with the neuroadapted JHM strain of mouse hepatitis virus (JHMV) resulted in increased mortality that was not associated with impaired ability to control viral replication but enhanced T cell and macrophage infiltration into the CNS. IFN-γ secretion from virus-specific CD4+ and CD8+ T cells isolated from infected EBI3−/− mice was augmented while IL-10 expression muted in comparison to infected WT mice. These data demonstrate a regulatory role for EBI3-associated cytokines in controlling host responses following CNS viral infection.",,"['Tirotta, Emanuele', 'Duncker, Patrick', 'Oak, Jean', 'Klaus, Suzi', 'Tsukamoto, Michelle R.', 'Gov, Lanny', 'Lane, Thomas E.']",,,,
,PMC,Murine Hepatitis Virus nsp4 N258T Mutants Are Not Temperature-Sensitive,http://dx.doi.org/10.1016/j.virol.2012.10.001,PMC3804408,,,"Coronavirus replicase nsp4 is critical for virus-induced membrane modifications. An nsp4 mutant (N258T) of murine hepatitis virus (MHV) has been reported to be temperature-sensitive (ts) and to alter membrane targeting. We engineered and recovered all four possible codon variants of N258T in the cloned MHV-A59 background. All mutant viruses demonstrated impaired replication compared to wildtype MHV, but no nsp4 N258T mutant virus was ts, and all variants colocalized with viral protein markers for replication complexes, but not with markers for mitochondria. This study emphasizes that complete genome sequencing may be necessary, even with directed and confirmed reverse genetic mutants.",,"['Beachboard, Dia C.', 'Lu, Xiaotao', 'Baker, Susan C.', 'Denison, Mark R.']",,,,
,PMC,"Synthesis and Anti-influenza A Virus Activity of 2,2-Dialkylamantadines and Related Compounds",http://dx.doi.org/10.1021/ml300279b,PMC4025864,,,"[Image: see text] The synthesis of several 2,2-dialkyladamantyl-1-amines through the combination of a Ritter reaction with a Wagner–Meerwein rearrangement from noradamantane alcohols is reported. Several of the novel amines displayed low micromolar activities against several H1N1 influenza virus strains, including the amantadine-resistant A/PuertoRico/8/34 strain. Most of the compounds did not show cytotoxicity for MDCK cells.",,"['Torres, Eva', 'Fernández, Roser', 'Miquet, Stéphanie', 'Font-Bardia, Mercè', 'Vanderlinden, Evelien', 'Naesens, Lieve', 'Vázquez, Santiago']",,,,
,PMC,Crystal Structure of Bovine Coronavirus Spike Protein Lectin Domain,http://dx.doi.org/10.1074/jbc.M112.418210,PMC3516740,,,"The spike protein N-terminal domains (NTDs) of bovine coronavirus (BCoV) and mouse hepatitis coronavirus (MHV) recognize sugar and protein receptors, respectively, despite their significant sequence homology. We recently determined the crystal structure of MHV NTD complexed with its protein receptor murine carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), which surprisingly revealed a human galectin (galactose-binding lectin) fold in MHV NTD. Here, we have determined at 1.55 Å resolution the crystal structure of BCoV NTD, which also has the human galectin fold. Using mutagenesis, we have located the sugar-binding site in BCoV NTD, which overlaps with the galactose-binding site in human galectins. Using a glycan array screen, we have identified 5-N-acetyl-9-O-acetylneuraminic acid as the preferred sugar substrate for BCoV NTD. Subtle structural differences between BCoV and MHV NTDs, primarily involving different conformations of receptor-binding loops, explain why BCoV NTD does not bind CEACAM1 and why MHV NTD does not bind sugar. These results suggest a successful viral evolution strategy in which coronaviruses stole a galectin from hosts, incorporated it into their spike protein, and evolved it into viral receptor-binding domains with altered sugar specificity in contemporary BCoV or novel protein specificity in contemporary MHV.",,"['Peng, Guiqing', 'Xu, Liqing', 'Lin, Yi-Lun', 'Chen, Lang', 'Pasquarella, Joseph R.', 'Holmes, Kathryn V.', 'Li, Fang']",,,,
,PMC,Disease invasion: impacts on biodiversity and human health,http://dx.doi.org/10.1098/rstb.2012.0331,PMC3427568,,,"An introduction to the theme issue that includes papers that identify how, where and why infectious diseases in wildlife emerge, while also addressing their possible conservation impacts.",,"['Cunningham, Andrew A.', 'Dobson, Andrew P.', 'Hudson, Peter J.']",,,,
,PMC,National and international policies to mitigate disease threats,http://dx.doi.org/10.1098/rstb.2011.0373,PMC3427563,,,"To devise and implement effective health policy, we must define the problem, choose the tools, craft the policy, build consensus, set goals and deadlines, raise funds and take action. Success or failure depends on the perception of risk, the strength of the underlying science, the efficacy of the technology, ownership and intellectual property, the conflict between individual and public health, the choice of weaker (guidelines) and stronger (law) policy instruments, the level of public interest, political opportunity, institutional inertia, mechanisms for enforcement and who foots the bill. All these things considered, this paper is a brief policy-making guide by example, illustrating some achievements and disappointments with reference to cholera, drug-resistant tuberculosis, HIV/AIDS and rabies.",,"Dye, Christopher",,,,
,PMC,Incubation period as part of the case definition of severe respiratory illness caused by a novel coronavirus,,PMC3722063,,,"Due to non-specific symptoms following acute respiratory viral infections, it is difficult for many countries without on-going transmission of a novel coronavirus to rule out other possibilities including influenza in advance of isolating imported febrile individuals with a possible exposure history. The incubation period helps differential diagnosis and up to two days is suggestive of influenza. It is worth accounting for the incubation period as part of the case definition of novel coronavirus infection.",,"['Nishiura, H.', 'Mizumoto, K.', 'Ejima, K.', 'Zhong, Y.', 'Cowling, B.J.', 'Omori, R.']",,,,
,PMC,Chinese herbs combined with Western medicine for severe acute respiratory syndrome (SARS),http://dx.doi.org/10.1002/14651858.CD004882.pub3,PMC6993561,,,"BACKGROUND: Severe acute respiratory syndrome (SARS) is an acute respiratory disease caused by a novel coronavirus, which first appeared in Foshan City, China on 22 December 2002. Chinese herbs were used in its treatment. OBJECTIVES: To evaluate the possible effectiveness and safety of Chinese herbs combined with Western medicines versus Western medicines alone for SARS patients. SEARCH METHODS: We searched CENTRAL 2012, Issue 3, MEDLINE (1966 to February Week 4, 2012), EMBASE (1990 to March 2012) and the Chinese Biomedical Literature (Issue 3, 2012). SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi‐RCTs of Chinese herbs combined with Western medicines versus Western medicines alone for patients diagnosed with SARS. DATA COLLECTION AND ANALYSIS: Two review authors (XL, MZ) independently extracted trial data. We extracted dichotomous and continuous data with 95% confidence intervals (CI). For dichotomous data, we used risk ratio (RR). For continuous data, we calculated mean differences (MD). We calculated overall results based on the random‐effects model if heterogeneity existed between studies. If no heterogeneity was detected between the studies, we used the fixed‐effect model. We used the Z score and the Chi(2) test with significance being set at P < 0.05 to test heterogeneity. No severe adverse events were reported. MAIN RESULTS: We included 12 RCTs and one quasi‐RCT. A total of 640 SARS patients and 12 Chinese herbs were identified. We did not find Chinese herbs combined with Western medicines decreased mortality versus Western medicines alone. Two herbs may improve symptoms. Five herbs may improve lung infiltrate absorption. Four herbs may decrease the dosage of corticosteroids. Three herbs may improve the quality of life of SARS patients. One herb may shorten the length of hospital stay. AUTHORS' CONCLUSIONS: Chinese herbs combined with Western medicines made no difference in decreasing mortality versus Western medicines alone. It is possible that Chinese herbs combined with Western medicines may improve symptoms, quality of life and absorption of pulmonary infiltration, and decrease the corticosteroid dosage for SARS patients. The evidence is weak because of the poor quality of the included trials. Long‐term follow‐up of these included trials is needed.",,"['Liu, Xuemei', 'Zhang, Mingming', 'He, Lin', 'Li, Youping']",,,,
,PMC,Infectious disease experts monitor outbreaks of enterovirus 71 in Asia,http://dx.doi.org/10.1503/cmaj.109-4291,PMC3478366,,,,,"Eggertson, Laura",,,,
,PMC,Influenza vaccination coverage across ethnic groups in Canada,http://dx.doi.org/10.1503/cmaj.111628,PMC3478352,,,"BACKGROUND: The success of influenza vaccination campaigns may be suboptimal if subgroups of the population face unique barriers or have misconceptions about vaccination. We conducted a national study to estimate influenza vaccine coverage across 12 ethnic groups in Canada to assess the presence of ethnic disparities. METHODS: We pooled responses to the Canadian Community Health Survey between 2003 and 2009 (n = 437 488). We estimated ethnicity-specific self-reported influenza vaccine coverage for the overall population, for people aged 65 years and older, and for people aged 12–64 years with and without chronic conditions. We used weighted logistic regression models to examine the association between ethnicity and influenza vaccination, adjusting for sociodemographic factors and health status. RESULTS: Influenza vaccination coverage ranged from 25% to 41% across ethnic groups. After adjusting for sociodemographic factors and health status for people aged 12 years and older, all ethnic groups were more likely to have received a vaccination against influenza than people who self-identified as white, with the exception of those who self-identified as black (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.88–1.15). Compared with white Canadians, Canadians of Filipino (OR 2.00, 95% CI 1.67–2.40) and Southeast Asian (OR 1.66, 95% CI 1.36–2.03) descent had the greatest likelihood of having received vaccination against influenza. INTERPRETATION: Influenza vaccine coverage in Canada varies by ethnicity. Black and white Canadians have the lowest uptake of influenza vaccine of the ethnic groups represented in our study. Further research is needed to understand the facilitators, barriers and misconceptions relating to vaccination that exist across ethnic groups, and to identify promotional strategies that may improve uptake among black and white Canadians.",,"['Quach, Susan', 'Hamid, Jemila S.', 'Pereira, Jennifer A.', 'Heidebrecht, Christine L.', 'Deeks, Shelley L.', 'Crowcroft, Natasha S.', 'Quan, Sherman D.', 'Brien, Stephanie', 'Kwong, Jeffrey C.']",,,,
,PMC,Structural basis for multifunctional roles of mammalian aminopeptidase N,http://dx.doi.org/10.1073/pnas.1210123109,PMC3497818,,,"Mammalian aminopeptidase N (APN) plays multifunctional roles in many physiological processes, including peptide metabolism, cell motility and adhesion, and coronavirus entry. Here we determined crystal structures of porcine APN at 1.85 Å resolution and its complexes with a peptide substrate and a variety of inhibitors. APN is a cell surface-anchored and seahorse-shaped zinc-aminopeptidase that forms head-to-head dimers. Captured in a catalytically active state, these structures of APN illustrate a detailed catalytic mechanism for its aminopeptidase activity. The active site and peptide-binding channel of APN reside in cavities with wide openings, allowing easy access to peptides. The cavities can potentially open up further to bind the exposed N terminus of proteins. The active site anchors the N-terminal neutral residue of peptides/proteins, and the peptide-binding channel binds the remainder of the peptides/proteins in a sequence-independent fashion. APN also provides an exposed outer surface for coronavirus binding, without its physiological functions being affected. These structural features enable APN to function ubiquitously in peptide metabolism, interact with other proteins to mediate cell motility and adhesion, and serve as a coronavirus receptor. This study elucidates multifunctional roles of APN and can guide therapeutic efforts to treat APN-related diseases.",,"['Chen, Lang', 'Lin, Yi-Lun', 'Peng, Guiqing', 'Li, Fang']",,,,
,PMC,Nucleotide-Resolution Profiling of RNA Recombination in the Encapsidated Genome of a Eukaryotic RNAVirus by Next-Generation Sequencing,http://dx.doi.org/10.1016/j.jmb.2012.10.005,PMC3502730,,,"Next-Generation Sequencing has been used in numerous investigations to characterize andquantifythe genetic diversity of a virus samplethrough the mapping of polymorphisms and measurement of mutation frequencies.Next-Generation Sequencing has also been employed to identifyrecombinationevents occurring within the genomes of higher organisms, for example, detecting alternative RNA splicing events and oncogenic chromosomal rearrangements. Here, we combine these two approaches toprofile RNA recombination within the encapsidated genome of a eukaryotic RNA virus, Flock House Virus. We detect hundreds of thousands of recombination events, with single-nucleotide resolution, which result indiversity in the encapsidated genome rivaling that due to mismatch mutation. We detect previously identified Defective-RNAs as well as many other abundant and novel Defective-RNAs. Our approach is exceptionally sensitive, unbiased, and requires no prior knowledge beyond the virus genome sequence. RNA recombination is a powerful driving force behind the evolution and adaptation of RNA viruses. The strategy implemented here is widely applicable and provides a highly detailed description of the complex mutational landscape of the transmissible viral genome.",,"['Routh, Andrew', 'Ordoukhanian, Phillip', 'Johnson, John E.']",,,,
,PMC,An octamer of enolase from Streptococcus suis,http://dx.doi.org/10.1007/s13238-012-2040-7,PMC4875344,,,"Enolase is a conserved cytoplasmic metalloenzyme existing universally in both eukaryotic and prokaryotic cells. The enzyme can also locate on the cell surface and bind to plasminogen, via which contributing to the mucosal surface localization of the bacterial pathogens and assisting the invasion into the host cells. The functions of the eukaryotic enzymes on the cell surface expression (including T cells, B cells, neutrophils, monocytoes, neuronal cells and epithelial cells) are not known. Streptococcus suis serotype 2 (S. suis 2, SS2) is an important zoonotic pathogen which has recently caused two large-scale outbreaks in southern China with severe streptococcal toxic shock syndrome (STSS) never seen before in human sufferers. We recently identified the SS2 enolase as an important protective antigen which could protect mice from fatal S.suis 2 infection. In this study, a 2.4-angstrom structure of the SS2 enolase is solved, revealing an octameric arrangement in the crystal. We further demonstrated that the enzyme exists exclusively as an octamer in solution via a sedimentation assay. These results indicate that the octamer is the biological unit of SS2 enolase at least in vitro and most likely in vivo as well. This is, to our knowledge, the first comprehensive characterization of the SS2 enolase octamer both structurally and biophysically, and the second octamer enolase structure in addition to that of Streptococcus pneumoniae. We also investigated the plasminogen binding property of the SS2 enzyme.",,"['Lu, Qiong', 'Lu, Hao', 'Qi, Jianxun', 'Lu, Guangwen', 'Gao, George F.']",,,,
,PMC,"Excess Mortality Associated With Influenza A and B Virus in Hong Kong, 1998–2009",http://dx.doi.org/10.1093/infdis/jis628,PMC3502382,,,"Background. Although deaths associated with laboratory-confirmed influenza virus infections are rare, the excess mortality burden of influenza estimated from statistical models may more reliably quantify the impact of influenza in a population. Methods. We applied age-specific multiple linear regression models to all-cause and cause-specific mortality rates in Hong Kong from 1998 through 2009. The differences between estimated mortality rates in the presence or absence of recorded influenza activity were used to estimate influenza-associated excess mortality. Results. The annual influenza-associated all-cause excess mortality rate was 11.1 (95% confidence interval [CI], 7.2–14.6) per 100 000 person-years. We estimated an average of 751 (95% CI, 488–990) excess deaths associated with influenza annually from 1998 through 2009, with 95% of the excess deaths occurring in persons aged ≥65 years. Most of the influenza-associated excess deaths were from respiratory (53%) and cardiovascular (18%) causes. Influenza A(H3N2) epidemics were associated with more excess deaths than influenza A(H1N1) or B during the study period. Conclusions. Influenza was associated with a substantial number of excess deaths each year, mainly among the elderly, in Hong Kong in the past decade. The influenza-associated excess mortality rates were generally similar in Hong Kong and the United States.",,"['Wu, Peng', 'Goldstein, Edward', 'Ho, Lai Ming', 'Yang, Lin', 'Nishiura, Hiroshi', 'Wu, Joseph T.', 'Ip, Dennis K. M.', 'Chuang, Shuk-Kwan', 'Tsang, Thomas', 'Cowling, Benjamin J.']",,,,
,PMC,Lifting the lid on toilet plume aerosol: A literature review with suggestions for future research,http://dx.doi.org/10.1016/j.ajic.2012.04.330,PMC4692156,,,"BACKGROUND: The potential risks associated with “toilet plume” aerosols produced by flush toilets is a subject of continuing study. This review examines the evidence regarding toilet plume bioaerosol generation and infectious disease transmission. METHODS: The peer-reviewed scientific literature was searched to identify articles related to aerosol production during toilet flushing, as well as epidemiologic studies examining the potential role of toilets in infectious disease outbreaks. RESULTS: The studies demonstrate that potentially infectious aerosols may be produced in substantial quantities during flushing. Aerosolization can continue through multiple flushes to expose subsequent toilet users. Some of the aerosols desiccate to become droplet nuclei and remain adrift in the air currents. However, no studies have yet clearly demonstrated or refuted toilet plume-related disease transmission, and the significance of the risk remains largely uncharacterized. CONCLUSION: Research suggests that toilet plume could play a contributory role in the transmission of infectious diseases. Additional research in multiple areas is warranted to assess the risks posed by toilet plume, especially within health care facilities.",,"['Johnson, David L.', 'Mead, Kenneth R.', 'Lynch, Robert A.', 'Hirst, Deborah V.L.']",,,,
,PMC,CCL2 affects β-amyloidosis and progressive neurocognitive dysfunction in a mouse model of Alzheimer’s disease,http://dx.doi.org/10.1016/j.neurobiolaging.2012.08.009,PMC4011558,,,"Neuroinflammation affects the pathobiology of Alzheimer’s disease (AD). Notably, beta-amyloid (Aβ) deposition induces microglial activation and the subsequent production of pro-inflammatory neurotoxic factors. In maintaining brain homeostasis, microglia plasticity also enables phenotypic transition between toxic and trophic activation states. One important control for such cell activation is through the CC-chemokine ligand 2 (CCL2) and its receptor, the CC-chemokine receptor 2 (CCR2). Both affect microglia and peripheral macrophage immune responses and for the latter, cell ingress across the blood brain barrier. However, how CCL2-CCR2 signaling contributes to AD pathogenesis is not well understood. To this end, we report that CCL2 deficiency influences behavioral abnormalities and disease progression in Aβ precursor protein/presenilin-1 double-transgenic mice. Here, increased cortical and hippocampal Aβ deposition is coincident with the formulation of Aβ oligomers. Deficits in peripheral Aβ clearance and in scavenger, neuroprogenitor and microglial cell functions are linked to deficient Aβ uptake. All can serve to accelerate memory dysfunction. Taken together, these data support a role of CCL2 in innate immune functions relevant to AD pathogenesis.",,"['Kiyota, Tomomi', 'Gendelman, Howard E.', 'Weir, Robert A.', 'Higgins, E. Elizabeth', 'Zhang, Gang', 'Jain, Mohit']",,,,
,PMC,Efficient −2 frameshifting by mammalian ribosomes to synthesize an additional arterivirus protein,http://dx.doi.org/10.1073/pnas.1211145109,PMC3491471,,,"Programmed −1 ribosomal frameshifting (−1 PRF) is a gene-expression mechanism used to express many viral and some cellular genes. In contrast, efficient natural utilization of −2 PRF has not been demonstrated previously in eukaryotic systems. Like all nidoviruses, members of the Arteriviridae (a family of positive-stranded RNA viruses) express their replicase polyproteins pp1a and pp1ab from two long ORFs (1a and 1b), where synthesis of pp1ab depends on −1 PRF. These polyproteins are posttranslationally cleaved into at least 13 functional nonstructural proteins. Here we report that porcine reproductive and respiratory syndrome virus (PRRSV), and apparently most other arteriviruses, use an additional PRF mechanism to access a conserved alternative ORF that overlaps the nsp2-encoding region of ORF1a in the +1 frame. We show here that this ORF is translated via −2 PRF at a conserved G_GUU_UUU sequence (underscores separate ORF1a codons) at an estimated efficiency of around 20%, yielding a transframe fusion (nsp2TF) with the N-terminal two thirds of nsp2. Expression of nsp2TF in PRRSV-infected cells was verified using specific Abs, and the site and direction of frameshifting were determined via mass spectrometric analysis of nsp2TF. Further, mutagenesis showed that the frameshift site and an unusual frameshift-stimulatory element (a conserved CCCANCUCC motif 11 nucleotides downstream) are required to direct efficient −2 PRF. Mutations preventing nsp2TF expression impair PRRSV replication and produce a small-plaque phenotype. Our findings demonstrate that −2 PRF is a functional gene-expression mechanism in eukaryotes and add another layer to the complexity of arterivirus genome expression.",,"['Fang, Ying', 'Treffers, Emmely E.', 'Li, Yanhua', 'Tas, Ali', 'Sun, Zhi', 'van der Meer, Yvonne', 'de Ru, Arnoud H.', 'van Veelen, Peter A.', 'Atkins, John F.', 'Snijder, Eric J.', 'Firth, Andrew E.']",,,,
,PMC,Specificity of the E1-E2-E3 Enzymatic Cascade for Ubiquitin C-terminal Sequences Identified by Phage Display,http://dx.doi.org/10.1021/cb300339p,PMC4652587,,,"Ubiquitin (UB) is a protein modifier that regulates many essential cellular processes. To initiate protein modification by UB, the E1 enzyme activates the C-terminal carboxylate of UB to launch its transfer through the E1-E2-E3 cascade onto target proteins. In this study, we used phage display to profile the specificity of the two human E1 enzymes, Ube1 and Uba6, towards the C-terminal sequence of UB ending with (71)LRLRGG(76). Phage selection revealed that while Arg72 of UB is absolutely required for E1 recognition, UB residues at positions 71, 73 and 74 can be replaced with bulky aromatic side chains, and Gly75 of UB can be changed to Ser, Asp and Asn for efficient E1 activation. We have thus found that the E1 enzymes have substantial promiscuity regarding the UB C-terminal sequence. The UB variants from phage selection can also be transferred from E1 to E2 enzymes, however, they are blocked from further transfer to the E3 enzymes. This suggests that the C-terminal sequence of UB is important for its discharge from E2 and subsequent transfer to E3. In addition, we observed that the Leu73Phe and Leu73Tyr single mutants of UB are resistant to cleavage by deubiquitinating enzymes (DUBs), although they can be assembled by the E1-E2-E3 cascade into poly-UB chains, thus indicating differences in UB C-terminal specificities between the E1 and DUBs. Consequently these UB mutants may provide stability to UB polymers attached to cellular proteins and facilitate the elucidation of the biological signals encoded in the UB chains.",,"['Zhao, Bo', 'Bhuripanyo, Karan', 'Schneider, Jeffrey', 'Zhang, Keya', 'Schindelin, Hermann', 'Boone, David', 'Yin, Jun']",,,,
,PMC,Influenza Viral RNA Detection in Blood as a Marker to Predict Disease Severity in Hematopoietic Cell Transplant Recipients,http://dx.doi.org/10.1093/infdis/jis610,PMC3502377,,,"Influenza RNA in blood (viremia) was detected in 9 of 79 (11.4%) hematopoietic cell transplant recipients with influenza, and was less frequently observed in patients with upper respiratory tract disease only and more frequently in patients infected with 2009 pandemic influenza A/H1N1 strain (versus seasonal strains). Viremia increased the risk of progression to lower respiratory tract disease (LRD), hypoxemia, respiratory failure, and overall and influenza-related death. Among patients with LRD, viremia was associated with increased hazards of overall and influenza-associated death (hazard ratio 3.5, 1.1–12). Thus, influenza viremia may serve as marker for overall poor outcome.",,"['Choi, Su-Mi', 'Xie, Hu', 'Campbell, Angela P.', 'Kuypers, Jane', 'Leisenring, Wendy', 'Boudreault, Alexandre A.', 'Englund, Janet A.', 'Corey, Lawrence', 'Boeckh, Michael']",,,,
,PMC,Preclinical Profile and Characterization of the Hepatitis C Virus NS3 Protease Inhibitor Asunaprevir (BMS-650032),http://dx.doi.org/10.1128/AAC.01186-12,PMC3457370,,,"Asunaprevir (ASV; BMS-650032) is a hepatitis C virus (HCV) NS3 protease inhibitor that has demonstrated efficacy in patients chronically infected with HCV genotype 1 when combined with alfa interferon and/or the NS5A replication complex inhibitor daclatasvir. ASV competitively binds to the NS3/4A protease complex, with K(i) values of 0.4 and 0.24 nM against recombinant enzymes representing genotypes 1a (H77) and 1b (J4L6S), respectively. Selectivity was demonstrated by the absence of any significant activity against the closely related GB virus-B NS3 protease and a panel of human serine or cysteine proteases. In cell culture, ASV inhibited replication of HCV replicons representing genotypes 1 and 4, with 50% effective concentrations (EC(50)s) ranging from 1 to 4 nM, and had weaker activity against genotypes 2 and 3 (EC(50), 67 to 1,162 nM). Selectivity was again demonstrated by the absence of activity (EC(50), >12 μM) against a panel of other RNA viruses. ASV exhibited additive or synergistic activity in combination studies with alfa interferon, ribavirin, and/or inhibitors specifically targeting NS5A or NS5B. Plasma and tissue exposures in vivo in several animal species indicated that ASV displayed a hepatotropic disposition (liver-to-plasma ratios ranging from 40- to 359-fold across species). Twenty-four hours postdose, liver exposures across all species tested were ≥110-fold above the inhibitor EC(50)s observed with HCV genotype-1 replicons. Based on these virologic and exposure properties, ASV holds promise for future utility in a combination with other anti-HCV agents in the treatment of HCV-infected patients.",,"['McPhee, Fiona', 'Sheaffer, Amy K.', 'Friborg, Jacques', 'Hernandez, Dennis', 'Falk, Paul', 'Zhai, Guangzhi', 'Levine, Steven', 'Chaniewski, Susan', 'Yu, Fei', 'Barry, Diana', 'Chen, Chaoqun', 'Lee, Min S.', 'Mosure, Kathy', 'Sun, Li-Qiang', 'Sinz, Michael', 'Meanwell, Nicholas A.', 'Colonno, Richard J.', 'Knipe, Jay', 'Scola, Paul']",,,,
,PMC,A possible cross-talk between autophagy and apoptosis in generating an immune response in melanoma,http://dx.doi.org/10.1007/s10495-012-0745-y,PMC3747633,,,"Melanoma is the most aggressive form of skin cancer, responsible for the majority of skin cancer related deaths. Thus, the search for natural molecules which can effectively destroy tumors while promoting immune activation is essential for designing novel therapies against metastatic melanoma. Here, we report for the first time that a natural triterpenoid, Ganoderic Acid DM (GA-DM), induces an orchestrated autophagic and apoptotic cell death, as well as enhanced immunological responses via increased HLA class II presentation in melanoma cells. Annexin V staining and flow cytometry showed that GA-DM treatment induced apoptosis of melanoma cells, which was supported by a detection of increased Bax proteins, co-localization and elevation of Apaf-1 and cytochrome c, and a subsequent cleavage of caspases 9 and 3. Furthermore, GA-DM treatment initiated a possible cross-talk between autophagy and apoptosis as evidenced by increased levels of Beclin-1 and LC3 proteins, and their timely interplay with apoptotic and/or anti-apoptotic molecules in melanoma cells. Despite GA-DM's moderate cytotoxicity, viable cells expressed high levels of HLA class II proteins with improved antigen presentation and CD4+ T cell recognition. The antitumor efficacy of GA-DM was also investigated in vivo in murine B16 melanoma model, where GA-DM treatment slowed tumor formation with a significant reduction in tumor volume. Taken together, these findings demonstrate the potential of GA-DM as a natural chemo-immunotherapeutic capable of inducing a possible cross-talk between autophagy and apoptosis, as well as improved immune recognition for sustained melanoma tumor clearance.",,"['Hossain, Azim', 'Radwan, Faisal F. Y.', 'Doonan, Bently P.', 'God, Jason M.', 'Zhang, Lixia', 'Bell, Darwin P.', 'Haque, Azizul']",,,,
,PMC,Mechanisms by Which Ambient Humidity May Affect Viruses in Aerosols,http://dx.doi.org/10.1128/AEM.01658-12,PMC3457514,,,"Many airborne viruses have been shown to be sensitive to ambient humidity, yet the mechanisms responsible for this phenomenon remain elusive. We review multiple hypotheses, including water activity, surface inactivation, and salt toxicity, that may account for the association between humidity and viability of viruses in aerosols. We assess the evidence and limitations for each hypothesis based on findings from virology, aerosol science, chemistry, and physics. In addition, we hypothesize that changes in pH within the aerosol that are induced by evaporation may trigger conformational changes of the surface glycoproteins of enveloped viruses and subsequently compromise their infectivity. This hypothesis may explain the differing responses of enveloped viruses to humidity. The precise mechanisms underlying the relationship remain largely unverified, and attaining a complete understanding of them will require an interdisciplinary approach.",,"['Yang, Wan', 'Marr, Linsey C.']",,,,
,PMC,Primary care reform in China,http://dx.doi.org/10.3399/bjgp12X656946,PMC3459766,,,,,"['Wang, Yu', 'Wilkinson, Martin', 'Ng, Edward', 'Cheng, KK']",,,,
,PMC,The changing face of international medicine,http://dx.doi.org/10.7861/clinmedicine.12-5-405,PMC4953758,,,,,"Coltart, Cordelia",,,,
,PMC,New Approaches to Sepsis: Molecular Diagnostics and Biomarkers,http://dx.doi.org/10.1128/CMR.00016-12,PMC3485751,,,"Summary: Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies.",,"['Reinhart, Konrad', 'Bauer, Michael', 'Riedemann, Niels C.', 'Hartog, Christiane S.']",,,,
,PMC,Prevention of influenza in healthy children,http://dx.doi.org/10.1586/eri.12.106,PMC3763239,,,"Healthy children are high transmitters of influenza and can experience poor influenza outcomes. Many questions remain about the efficacy and impect of preventive measures because most existing studies report imprecise proxies of influenza incidence, do not follow subjects throughout the entire influenza season and across multiple influenza seasons, or do not control for important factors such as timing of implementation and social contact patterns. Modeling and simulation are key methodologies to answer questions regarding influenza prevention. While vaccination may be the most efficacious existing intervention, variations in circulating strains and children’s immune systems keep current vaccines from being fully protective, necessitating further clinical and economic studies and technology improvements. Hand hygiene appears to be an important adjunct but improving compliance, standardizing regimens and quantifying its impact remain challenging. Future studies should help better define the specific indications and circumstances for antiviral use and the role of nutritional supplements and nonpharmaceutical interventions.",,"['Lee, Bruce Y', 'Shah, Mirat']",,,,
,PMC,Development of novel entry inhibitors targeting emerging viruses,http://dx.doi.org/10.1586/eri.12.104,PMC3587779,,,"Emerging viral diseases pose a unique risk to public health, and thus there is a need to develop therapies. A current focus of funding agencies, and hence research, is the development of broad-spectrum antivirals, and in particular, those targeting common cellular pathways. The scope of this article is to review screening strategies and recent advances in this area, with a particular emphasis on antivirals targeting the step of viral entry for emerging lipid-enveloped viruses such as Ebola virus and SARS-coronavirus.",,"['Zhou, Yanchen', 'Simmons, Graham']",,,,
,PMC,Pathogenic characterization of a cervical lymph node derived from a patient with Kawasaki disease,,PMC3466979,,,"Kawasaki disease (KD) is the most common cause of multisystem vasculitis in childhood. Although cervical lymphadenitis is one of the major symptoms in KD, lymph node biopsy is rarely performed, because KD is usually diagnosed by clinical symptoms. A cervical lymph node biopsy was taken from a girl aged 1 year and 8 months who had suspected lymphoma, but she was diagnosed with KD after the biopsy. The cervical lymph node specimen was analyzed with multivirus real-time PCR that can detect >160 viruses, and unbiased direct sequencing with a next-generation DNA sequencer to detect potential pathogens in the lymph node. Histologically, focal necrosis with inflammatory cell infiltration, including neutrophils and macrophages, was observed in the marginal zone of the cervical lymph node, which was compatible with the acute phase of KD. Multivirus real-time PCR detected a low copy number of torque teno virus in the sample. Comprehensive direct sequencing of the cervical lymph node biopsy sample sequenced more than 8 million and 3 million reads from DNA and RNA samples, respectively. Bacterial genomes were detected in 0.03% and 1.79% of all reads in DNA and RNA samples, respectively. Although many reads corresponded to genomes of bacterial environmental microorganisms, Streptococcus spp. genome was detected in both DNA (77 reads) and RNA (2,925 reads) samples. Further studies are required to reveal any association of microbial or viral infection with the pathogenesis of KD.",,"['Katano, Harutaka', 'Sato, Seiichi', 'Sekizuka, Tsuyoshi', 'Kinumaki, Akiko', 'Fukumoto, Hitomi', 'Sato, Yuko', 'Hasegawa, Hideki', 'Morikawa, Shigeru', 'Saijo, Masayuki', 'Mizutani, Tetsuya', 'Kuroda, Makoto']",,,,
,PMC,Quantitative analysis of Glycyrrhizic acid from a polyherbal preparation using liquid chromatographic technique,http://dx.doi.org/10.4103/2231-4040.104711,PMC3560126,23378941,CC BY-NC-SA,"Glycyrrhizic acid has been used in Indian traditional medicine for ages. It is obtained from the root extract of Glycyrrhizaglabra. There is seasonal variation of Glycyrrhizic acid content in the roots of the plant. So a proper method for quantification of the same is necessary from the polyherbal preparation available in the market. A simple, rapid, sensitive and specific reverse phase high performance liquid chromatographic method have been developed for the quantitative estimation of glycyrrhizic acid from polyherbal preparation containing aqueous root extract of Glycyrrhizaglabra using a photodiode array detector. The identity confirmation was carried out using mass spectrometry. Baseline resolution of the glycyrrhizic acid peak was achieved on a reverse phase C18 column (125 mm × 4.0 mm, 5 μ) using an isocratic mobile phase consisting of 5.3 mM phosphate buffer and acetonitrile in the ratio 65:35 v/v. Chromatograms were monitored at 252 nm.5.3 mM phosphate buffer was replaced with 0.5mM ammonium acetate buffer in the mobile phase when MS detector was used. The method was found to be linear in the concentration range of 12.4 to124 μg/ml with a correlation co-efficient of 0.999. The limit of detection and the limit of quantitation were 3.08 μg/ml and 10.27 μg/ml respectively. The average recovery from three spike levels was 99.93 ± 0.26%. Identity confirmation of the chromatographic peak was achieved by electrospray ionization mass spectrometry and similar molecular ion peak was obtained for both sample and standard. The developed method is suitable for the routine analysis, stability testing and assay of glycyrrhizic acid from polyherbal preparations containing aqueous extracts of Glycyrrhizaglabra.",2012 Oct-Dec,"['De, Amit K.', 'Datta, Sriparna', 'Mukherjee, Arup']",J Adv Pharm Technol Res,,,
,PMC,Detecting viruses by using salivary diagnostics,,PMC4262792,,,"BACKGROUND: Diagnostics that involve the use of oral fluids have become increasingly available commercially in recent years and are of particular interest because of their relative ease of use, low cost and noninvasive collection of oral fluid for testing. TYPES OF STUDIES REVIEWED: The authors discuss the use of salivary diagnostics for virus detection with an emphasis on rapid detection of infection by using point-of-care devices. In particular, they review salivary diagnostics for human immunodeficiency virus, hepatitis C virus and human papillomavirus. Oral mucosal transudate contains secretory immunoglobulin (Ig) A, as well as IgM and IgG, which makes it a good source for immunodiagnostic-based devices. CLINICAL IMPLICATIONS: Because patients often visit a dentist more regularly than they do a physician, there is increased discussion in the dental community regarding the need for practitioners to be aware of salivary diagnostics and to be willing and able to administer these tests to their patients.",,"['Corstjens, Paul L.A.M.', 'Abrams, William R.', 'Malamud, Daniel']",,,,
,PMC,Respiratory Virus Detection in Immunocompromised Patients with FilmArray Respiratory Panel Compared to Conventional Methods,http://dx.doi.org/10.1128/JCM.00538-12,PMC3457462,,,"Respiratory virus infections cause significant morbidity and mortality in immunocompromised patients. Timely diagnosis is needed to provide optimal clinical care. Diagnostic tests routinely available at most institutions are limited by poor sensitivity and a slow turnaround time. We collected 90 respiratory samples from 87 immunocompromised patients (56 bronchoalveolar lavage and 34 nasopharyngeal aspirate samples) in order to compare the performance of routine respiratory virus testing available at our institution to the FilmArray respiratory panel assay, a novel diagnostic tool which utilizes multiplex PCR to test for 21 respiratory pathogens with a 1-h turnaround time. Samples with discordant results and 13 samples with concordant results underwent further verification testing by laboratory-developed real-time PCR. The FilmArray assay identified viral pathogens in more samples than did clinical testing (30/90 versus 16/90; McNemar P = 0.001). Most of the additional viral pathogens identified by the FilmArray respiratory panel assay that were confirmed by verification testing were pathogens not assessed by routine clinical tests, including rhinovirus/enterovirus, human metapneumovirus, and coronavirus. The FilmArray respiratory panel assay allowed for increased identification of respiratory viral pathogens in this cohort of immunocompromised patients.",,"['Hammond, Sarah P.', 'Gagne, Lisa S.', 'Stock, Shannon R.', 'Marty, Francisco M.', 'Gelman, Rebecca S.', 'Marasco, Wayne A.', 'Poritz, Mark A.', 'Baden, Lindsey R.']",,,,
,PMC,Multilocus Variable-Number Tandem-Repeat Analysis-Confirmed Emergence of a Macrolide Resistance-Associated Mutation in Mycoplasma pneumoniae during Macrolide Therapy for Interstitial Pneumonia in an Immunocompromised Child,http://dx.doi.org/10.1128/JCM.01248-12,PMC3457418,,,A child with Job's syndrome was treated for pneumonia due to Mycoplasma pneumoniae. A mixed population of wild-type bacteria and an A2059G mutant was detected during josamycin treatment failure. The same multilocus variable-number tandem-repeat analysis (MLVA) type (MLVA type I) was isolated before and after treatment failure. The child recovered after ciprofloxacin treatment.,,"['Hantz, Sébastien', 'Garnier, Fabien', 'Peuchant, Olivia', 'Menetrey, Céline', 'Charron, Alain', 'Ploy, Marie-Cécile', 'Bébéar, Cécile', 'Pereyre, Sabine']",,,,
,PMC,Endoplasmic reticulum stress regulates the innate immunity critical transcription factor interferon regulatory factor 3,http://dx.doi.org/10.4049/jimmunol.1102737,PMC3478468,,,"Interferon regulatory factor 3 (IRF3) regulates early type I IFNs and other genes involved in innate immunity. We have previously shown that cells undergoing an endoplasmic reticulum (ER) stress response called the “Unfolded Protein Response” (UPR) produce synergistically augmented IFN-β when stimulated with pattern recognition receptor agonists such as LPS Concomitant ER stress and LPS stimulation resulted in greater recruitment of the IRF3 transcription factor to ifnb1 gene regulatory elements. In this study, we utilized murine cells to demonstrate that both oxygen-glucose deprivation and pharmacologic UPR inducers trigger phosphorylation and nuclear translocation of IRF3, even in the absence of exogenous LPS. Different ER stressors utilized distinct mechanisms to activate IRF3: IRF3 phosphorylation due to calcium-mobilizing ER stress (thapsigargin treatment, oxygen-glucose deprivation) critically depended upon Stimulator of interferon gene (STING), an ER-resident nucleic acid-responsive molecule. However, calcium mobilization alone by ionomycin was insufficient for IRF3 phosphorylation. In contrast, other forms of ER stress (e.g., tunicamycin treatment) promote IRF3 phosphorylation independently of STING and Tank binding kinase 1 (TBK1). Rather, IRF3 activation by tunicamycin and 2-deoxyglucose was inhibited by AEBSF, a serine protease inhibitor that blocks ATF6 processing. Interfering with ER stress-induced IRF3 activation abrogated IFN-β synergy. Together, these data suggest ER stress primes cells to respond to innate immune stimuli by activating the IRF3 transcription factor. Our results also suggest certain types of ER stress accomplish IRF3 phosphorylation by co-opting existing innate immune pathogen response pathways. These data have implications for diseases involving ER stress and type I IFN.",,"['Liu, Yi-Ping', 'Zeng, Ling', 'Tian, Austin', 'Bomkamp, Ashley', 'Rivera, Daniel', 'Gutman, Delia', 'Barber, Glen N.', 'Olson, Julie K.', 'Smith, Judith A.']",,,,
,PMC,Professor Nanshan Zhong joins International Advisory Board of The Lancet Respiratory Medicine,http://dx.doi.org/10.3978/j.issn.2072-1439.2012.09.08,PMC3461064,,,,,"['Team, Editorial', 'Disease, Journal of Thoracic']",,,,
,PMC,Complete Genome Sequence of Porcine Epidemic Diarrhea Virus Strain AJ1102 Isolated from a Suckling Piglet with Acute Diarrhea in China,http://dx.doi.org/10.1128/JVI.01919-12,PMC3457323,,,"A diarrhea outbreak caused by porcine epidemic diarrhea virus (PEDV) has been observed in China since December 2010. We report here the complete genome sequence of PEDV strain AJ1102 isolated from a suckling piglet with acute diarrhea, which will help toward understanding the molecular and evolutionary characteristics of the epidemic PEDV in China.",,"['Bi, Jing', 'Zeng, Songlin', 'Xiao, Shaobo', 'Chen, Huanchun', 'Fang, Liurong']",,,,
,PMC,Myd88-Dependent Toll-Like Receptor 7 Signaling Mediates Protection from Severe Ross River Virus-Induced Disease in Mice,http://dx.doi.org/10.1128/JVI.00601-12,PMC3457316,,,"Arthralgia-associated alphaviruses, including chikungunya virus (CHIKV) and Ross River virus (RRV), pose significant public health threats because of their ability to cause explosive outbreaks of debilitating arthralgia and myalgia in human populations. Although the host inflammatory response is known to contribute to the pathogenesis of alphavirus-induced arthritis and myositis, the role that Toll-like receptors (TLRs), which are major regulators of host antiviral and inflammatory responses, play in the pathogenesis of alphavirus-induced arthritis and myositis has not been extensively studied. Using a mouse model of RRV-induced myositis/arthritis, we found that myeloid differentiation primary response gene 88 (Myd88)-dependent TLR7 signaling is involved in protection from severe RRV-associated disease. Infections of Myd88- and TLR7-deficient mouse strains with RRV revealed that both Myd88 and TLR7 significantly contributed to protection from RRV-induced mortality, and both mouse strains exhibited more severe tissue damage than wild-type (WT) mice following RRV infection. While viral loads were unchanged in either Myd88 or TLR7 knockout mice compared to WT mice at early times postinfection, both Myd88 and TLR7 knockout mice exhibited higher viral loads than WT mice at late times postinfection. Furthermore, while high levels of RRV-specific antibody were produced in TLR7-deficient mice, this antibody had very little neutralizing activity and had lower affinity than WT antibody. Additionally, TLR7- and Myd88-deficient mice showed defects in germinal center activity, suggesting that TLR7-dependent signaling is critical for the development of protective antibody responses against RRV.",,"['Neighbours, Lauren M.', 'Long, Kristin', 'Whitmore, Alan C.', 'Heise, Mark T.']",,,,
,PMC,NS1-Truncated Live Attenuated Virus Vaccine Provides Robust Protection to Aged Mice from Viral Challenge,http://dx.doi.org/10.1128/JVI.01131-12,PMC3457311,,,"Immunological changes associated with age contribute to the high rates of influenza virus morbidity and mortality in the elderly. Compounding this problem, aged individuals do not respond to vaccination as well as younger, healthy adults. Efforts to increase protection to this demographic group are of utmost importance, as the proportion of the population above the age of 65 is projected to increase in the coming decade. Using a live influenza virus with a truncated nonstructural protein 1 (NS1), we are able to stimulate cellular and humoral immune responses of aged mice comparable to levels seen in young mice. Impressively, a single vaccination provided protection following stringent lethal challenge in aged mice.",,"['Pica, Natalie', 'Langlois, Ryan A.', 'Krammer, Florian', 'Margine, Irina', 'Palese, Peter']",,,,
,PMC,Protective Capacity of Virus-Specific T Cell Receptor-Transduced CD8 T Cells In Vivo,http://dx.doi.org/10.1128/JVI.01472-12,PMC3457306,,,"The transfer of T cell receptor (TCR) genes by viral vectors represents a promising technique to generate antigen-specific T cells for adoptive immunotherapy. TCR-transduced T cells specific for infectious pathogens have been described, but their protective function in vivo has not yet been examined. Here, we demonstrate that CD8 T cells transduced with the P14 TCR specific for the gp33 epitope of lymphocytic choriomeningitis virus exhibit protective activities in both viral and bacterial infection models in mice.",,"['Mueller, Katja', 'von Mässenhausen, Anne', 'Aichele, Ulrike', 'Stärck, Lilian', 'Leisegang, Matthias', 'Uckert, Wolfgang', 'Pircher, Hanspeter']",,,,
,PMC,Cleavage Activation of the Human-Adapted Influenza Virus Subtypes by Matriptase Reveals both Subtype and Strain Specificities,http://dx.doi.org/10.1128/JVI.00306-12,PMC3457293,,,"Cleavage activation of the hemagglutinin (HA) precursor is an essential step in the influenza virus replication cycle that is driven by host cell proteases. HA cleavage activation is required for virus-endosome membrane fusion and the subsequent release of the influenza virus genome into the cytoplasm. Previous studies have determined that HA cleavage is most likely driven by either membrane-bound or extracellular trypsin-like proteases that reside in the respiratory tract. However, there is still uncertainty regarding which proteases are critical for HA cleavage in vivo. Therefore, further investigation of HA cleavage activation is needed in order to gain insight into the critical proteases involved. Matriptase is a member of the type II transmembrane serine protease family that is highly expressed in a membrane-bound form throughout the respiratory tract. One feature of matriptase is that, once activated, the catalytic domain is secreted into the extracellular space and so serves as a functional extracellular protease. In this study, we have determined that the secreted, catalytic domain of matriptase has the ability to cleave and activate HA from the influenza virus H1 subtype but not the H2 and H3 subtypes. Furthermore, matriptase selectively cleaved the HA of particular strains within the H1 subtype, revealing both subtype and H1 strain specificity. Matriptase was also found to activate thrombolytic zymogens that have been shown to cleave and activate the influenza virus HA. Our data demonstrate that matriptase has the ability to cleave HA directly or indirectly by activating HA-cleaving zymogens.",,"['Hamilton, Brian S.', 'Gludish, David W. J.', 'Whittaker, Gary R.']",,,,
,PMC,Control of Early Theiler's Murine Encephalomyelitis Virus Replication in Macrophages by Interleukin-6 Occurs in Conjunction with STAT1 Activation and Nitric Oxide Production,http://dx.doi.org/10.1128/JVI.01402-12,PMC3457289,,,"During Theiler's murine encephalomyelitis virus (TMEV) infection of macrophages, it is thought that high interleukin-6 (IL-6) levels contribute to the demyelinating disease found in chronically infected SJL/J mice but absent in B10.S mice capable of clearing the infection. Therefore, IL-6 expression was measured in TMEV-susceptible SJL/J and TMEV-resistant B10.S macrophages during their infection with TMEV DA strain or responses to lipopolysaccharide (LPS) or poly(I · C). Unexpectedly, IL-6 production was greater in B10.S macrophages than SJL/J macrophages during the first 24 h after stimulation with TMEV, LPS, or poly(I · C). Further experiments showed that in B10.S, SJL/J, and RAW264.7 macrophage cells, IL-6 expression was dependent on extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) and enhanced by exogenous IL-12. In SJL/J and RAW264.7 macrophages, exogenous IL-6 resulted in decreased TMEV replication, earlier activation of STAT1 and STAT3, production of nitric oxide, and earlier upregulation of several antiviral genes downstream of STAT1. However, neither inhibition of IL-6-induced nitric oxide nor knockdown of STAT1 diminished the early antiviral effect of exogenous IL-6. In addition, neutralization of endogenous IL-6 from SJL/J macrophages with Fab antibodies did not exacerbate early TMEV infection. Therefore, endogenous IL-6 expression after TMEV infection is dependent on ERK MAPK, enhanced by IL-12, but too slow to decrease viral replication during early infection. In contrast, exogenous IL-6 enhances macrophage control of TMEV infection through preemptive antiviral nitric oxide production and antiviral STAT1 activation. These results indicate that immediate-early production of IL-6 could protect macrophages from TMEV infection.",,"['Moore, Tyler C.', 'Bush, Katherine L.', 'Cody, Liz', 'Brown, Deborah M.', 'Petro, Thomas M.']",,,,
,PMC,Hepatitis C Virus-Induced Autophagy Is Independent of the Unfolded Protein Response,http://dx.doi.org/10.1128/JVI.01667-12,PMC3457281,,,"Hepatitis C virus (HCV) has been shown to induce autophagy and the unfolded protein response (UPR), but the mechanistic link between the induction of these two cellular processes remains unclear. We demonstrate here that HCV infection induces autophagy, as judged by accumulation of lipidated LC3-II, and that this induction occurs rapidly after infection, preceding the stimulation of the UPR, which occurs only at later stages, after the viral envelope glycoproteins have been expressed to high levels. Furthermore, both genotype 1b and 2a subgenomic replicons expressing nonstructural (NS3-5B) proteins and JFH-1 virus lacking the envelope glycoproteins potently induced autophagy in the absence of detectable UPR. This ability was also shared by a subgenomic replicon derived from the related GB virus B (GBV-B). We also show that small interfering RNA (siRNA)-mediated silencing of the key UPR inducer, Ire1, has no effect on HCV genome replication or the induction of autophagy, further demonstrating that the UPR is not required for these processes. Lastly, we demonstrate that the HCV replicase does not colocalize with autophagosomes, suggesting that the induction of autophagy is not required to generate the membrane platform for HCV RNA replication.",,"['Mohl, Bjorn-Patrick', 'Tedbury, Philip R.', 'Griffin, Stephen', 'Harris, Mark']",,,,
,PMC,Expression of the Infectious Salmon Anemia Virus Receptor on Atlantic Salmon Endothelial Cells Correlates with the Cell Tropism of the Virus,http://dx.doi.org/10.1128/JVI.00047-12,PMC3457268,,,"Infectious salmon anemia (ISA) is a World Organization for Animal Health (OIE)-listed disease of farmed Atlantic salmon, characterized by slowly developing anemia and circulatory disturbances. The disease is caused by ISA virus (ISAV) in the Orthomyxoviridae family; hence, it is related to influenza. Here we explore the pathogenesis of ISA by focusing on virus tropism, receptor tissue distribution, and pathological changes in experimentally and naturally infected Atlantic salmon. Using immunohistochemistry on ISAV-infected Atlantic salmon tissues with antibody to viral nucleoprotein, endotheliotropism was demonstrated. Endothelial cells lining the circulatory system were found to be infected, seemingly noncytolytic, and without vasculitis. No virus could be found in necrotic parenchymal cells. From endothelium, the virus budded apically and adsorbed to red blood cells (RBCs). No infection or replication within RBCs was detected, but hemophagocytosis was observed, possibly contributing to the severe anemia in fish with this disease. Similarly to what has been done in studies of influenza, we examined the pattern of virus attachment by using ISAV as a probe. Here we detected the preferred receptor of ISAV, 4-O-acetylated sialic acid (Neu4,5Ac(2)). To our knowledge, this is the first report demonstrating the in situ distribution of this sialic acid derivate. The pattern of virus attachment mirrored closely the distribution of infection, showing that the virus receptor is important for cell tropism, as well as for adsorption to RBCs.",,"['Aamelfot, Maria', 'Dale, Ole Bendik', 'Weli, Simon Chioma', 'Koppang, Erling Olaf', 'Falk, Knut']",,,,
,PMC,Complete Genome Sequences of Two Chinese Virulent Avian Coronavirus Infectious Bronchitis Virus Variants,http://dx.doi.org/10.1128/JVI.01895-12,PMC3457259,,,"Avian coronavirus infectious bronchitis virus (IBV) is variable, which causes many serotypes. Here we reported the complete genome sequences of two virulent IBV variants from China, GX-YL5 and GX-YL9, belonging to different serotypes. Differences between GX-YL5 and GX-YL9 were found mainly in stem-loop structure I in the predicted RNA secondary structure of open reading frame (ORF) 1b and the S protein gene fusion region, which will help us understand the molecular evolutionary mechanism of IBV and the disconcordance between the genotypes and serotypes of coronavirus.",,"['Mo, Meilan', 'Huang, Baicheng', 'Wei, Ping', 'Wei, Tianchao', 'Chen, Qiuying', 'Wang, Xiuying', 'Li, Meng', 'Fan, Wensheng']",,,,
,PMC,Hepatitis C Virus (HCV) Induces Formation of Stress Granules Whose Proteins Regulate HCV RNA Replication and Virus Assembly and Egress,http://dx.doi.org/10.1128/JVI.07101-11,PMC3457181,,,"Stress granules (SGs) are cytoplasmic structures that are induced in response to environmental stress, including viral infections. Here we report that hepatitis C virus (HCV) triggers the appearance of SGs in a PKR- and interferon (IFN)-dependent manner. Moreover, we show an inverse correlation between the presence of stress granules and the induction of IFN-stimulated proteins, i.e., MxA and USP18, in HCV-infected cells despite high-level expression of the corresponding MxA and USP18 mRNAs, suggesting that interferon-stimulated gene translation is inhibited in stress granule-containing HCV-infected cells. Finally, in short hairpin RNA (shRNA) knockdown experiments, we found that the stress granule proteins T-cell-restricted intracellular antigen 1 (TIA-1), TIA1-related protein (TIAR), and RasGAP-SH3 domain binding protein 1 (G3BP1) are required for efficient HCV RNA and protein accumulation at early time points in the infection and that G3BP1 and TIA-1 are required for intracellular and extracellular infectious virus production late in the infection, suggesting that they are required for virus assembly. In contrast, TIAR downregulation decreases extracellular infectious virus titers with little effect on intracellular RNA content or infectivity late in the infection, suggesting that it is required for infectious particle release. Collectively, these results illustrate that HCV exploits the stress granule machinery at least two ways: by inducing the formation of SGs by triggering PKR phosphorylation, thereby downregulating the translation of antiviral interferon-stimulated genes, and by co-opting SG proteins for its replication, assembly, and egress.",,"['Garaigorta, Urtzi', 'Heim, Markus H.', 'Boyd, Bryan', 'Wieland, Stefan', 'Chisari, Francis V.']",,,,
,PMC,Virome Analysis for Identification of Novel Mammalian Viruses in Bat Species from Chinese Provinces,http://dx.doi.org/10.1128/JVI.01394-12,PMC3457178,,,"Bats are natural hosts for a large variety of zoonotic viruses. This study aimed to describe the range of bat viromes, including viruses from mammals, insects, fungi, plants, and phages, in 11 insectivorous bat species (216 bats in total) common in six provinces of China. To analyze viromes, we used sequence-independent PCR amplification and next-generation sequencing technology (Solexa Genome Analyzer II; Illumina). The viromes were identified by sequence similarity comparisons to known viruses. The mammalian viruses included those of the Adenoviridae, Herpesviridae, Papillomaviridae, Retroviridae, Circoviridae, Rhabdoviridae, Astroviridae, Flaviridae, Coronaviridae, Picornaviridae, and Parvovirinae; insect viruses included those of the Baculoviridae, Iflaviridae, Dicistroviridae, Tetraviridae, and Densovirinae; fungal viruses included those of the Chrysoviridae, Hypoviridae, Partitiviridae, and Totiviridae; and phages included those of the Caudovirales, Inoviridae, and Microviridae and unclassified phages. In addition to the viruses and phages associated with the insects, plants, and bacterial flora related to the diet and habitation of bats, we identified the complete or partial genome sequences of 13 novel mammalian viruses. These included herpesviruses, papillomaviruses, a circovirus, a bocavirus, picornaviruses, a pestivirus, and a foamy virus. Pairwise alignments and phylogenetic analyses indicated that these novel viruses showed little genetic similarity with previously reported viruses. This study also revealed a high prevalence and diversity of bat astroviruses and coronaviruses in some provinces. These findings have expanded our understanding of the viromes of bats in China and hinted at the presence of a large variety of unknown mammalian viruses in many common bat species of mainland China.",,"['Wu, Zhiqiang', 'Ren, Xianwen', 'Yang, Li', 'Hu, Yongfeng', 'Yang, Jian', 'He, Guimei', 'Zhang, Junpeng', 'Dong, Jie', 'Sun, Lilian', 'Du, Jiang', 'Liu, Liguo', 'Xue, Ying', 'Wang, Jianmin', 'Yang, Fan', 'Zhang, Shuyi', 'Jin, Qi']",,,,
,PMC,Increased Viral Loads and Exacerbated Innate Host Responses in Aged Macaques Infected with the 2009 Pandemic H1N1 Influenza A Virus,http://dx.doi.org/10.1128/JVI.01571-12,PMC3457171,,,"In contrast to seasonal influenza virus infections, which typically cause significant morbidity and mortality in the elderly, the 2009 H1N1 virus caused severe infection in young adults. This phenomenon was attributed to the presence of cross-protective antibodies acquired by older individuals during previous exposures to H1N1 viruses. However, this hypothesis could not be empirically tested. To address this question, we compared viral replication and the development of the immune response in naïve young adult and aged female rhesus macaques infected with A/California/04/2009 H1N1 (CA04) virus. We show higher viral loads in the bronchoalveolar lavage (BAL) fluid and nasal and ocular swabs in aged animals, suggesting increased viral replication in both the lower and upper respiratory tracts. T cell proliferation was higher in the BAL fluid but delayed and reduced in peripheral blood in aged animals. This delay in proliferation correlated with a reduced frequency of effector CD4 T cells in old animals. Aged animals also mobilized inflammatory cytokines to higher levels in the BAL fluid. Finally, we compared changes in gene expression using microarray analysis of BAL fluid samples. Our analyses revealed that the largest difference in host response between aged and young adult animals was detected at day 4 postinfection, with a significantly higher induction of genes associated with inflammation and the innate immune response in aged animals. Overall, our data suggest that, in the absence of preexisting antibodies, CA04 infection in aged macaques is associated with changes in innate and adaptive immune responses that were shown to correlate with increased disease severity in other respiratory disease models.",,"['Josset, Laurence', 'Engelmann, Flora', 'Haberthur, Kristen', 'Kelly, Sara', 'Park, Byung', 'Kawoaka, Yoshi', 'García-Sastre, Adolfo', 'Katze, Michael G.', 'Messaoudi, Ilhem']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus nsp1 Facilitates Efficient Propagation in Cells through a Specific Translational Shutoff of Host mRNA,http://dx.doi.org/10.1128/JVI.01700-12,PMC3457165,,,"Severe acute respiratory syndrome (SARS) coronavirus (SCoV) is an enveloped virus containing a single-stranded, positive-sense RNA genome. Nine mRNAs carrying a set of common 5′ and 3′ untranslated regions (UTR) are synthesized from the incoming viral genomic RNA in cells infected with SCoV. A nonstructural SCoV nsp1 protein causes a severe translational shutoff by binding to the 40S ribosomal subunits. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5′UTR of host mRNA. However, the mechanism by which SCoV viral proteins are efficiently produced in infected cells in which host protein synthesis is impaired by nsp1 is unknown. In this study, we investigated the role of the viral UTRs in evasion of the nsp1-mediated shutoff. Luciferase activities were significantly suppressed in cells expressing nsp1 together with the mRNA carrying a luciferase gene, while nsp1 failed to suppress luciferase activities of the mRNA flanked by the 5′UTR of SCoV. An RNA-protein binding assay and RNA decay assay revealed that nsp1 bound to stem-loop 1 (SL1) in the 5′UTR of SCoV RNA and that the specific interaction with nsp1 stabilized the mRNA carrying SL1. Furthermore, experiments using an SCoV replicon system showed that the specific interaction enhanced the SCoV replication. The specific interaction of nsp1 with SL1 is an important strategy to facilitate efficient viral gene expression in infected cells, in which nsp1 suppresses host gene expression. Our data indicate a novel mechanism of viral gene expression control by nsp1 and give new insight into understanding the pathogenesis of SARS.",,"['Tanaka, Tomohisa', 'Kamitani, Wataru', 'DeDiego, Marta L.', 'Enjuanes, Luis', 'Matsuura, Yoshiharu']",,,,
,PMC,Cross-Species Transmission in the Speciation of the Currently Known Murinae-Associated Hantaviruses,http://dx.doi.org/10.1128/JVI.00021-12,PMC3457156,,,"To gain more insight into the phylogeny of Dabieshan virus (DBSV), carried by Niviventer confucianus and other Murinae-associated hantaviruses, genome sequences of novel variants of DBSV were recovered from Niviventer rats trapped in the mountainous areas of Wenzhou, China. Genetic analyses show that all known genetic variants of DBSV, including the ones identified in this study, are distinct from other Murinae-associated hantaviruses. DBSV variants show geographic clustering and high intraspecies diversity. The data suggest that DBSV is a distinct species in the genus Hantavirus. Interestingly, DBSV shows the highest sequence identity to Hantaan virus (HTNV), with a >7% difference in the sequences of the N, GPC, and L proteins, while N. confucianus is more closely related to Rattus norvegicus (the host of Seoul virus [SEOV]) than to Apodemus agrarius (the host of HTNV and Saaremaa virus [SAAV]). Further genetic analyses of all known Murinae-associated hantaviruses (both established and tentative species) show that many of them, including DBSV, may have originated from host switching. The estimation of evolutionary rates and divergence time supports the role of cross-species transmission in the evolution of Murinae-associated hantaviruses. The detection of positive selection suggests that genetic drift may contribute to the speciation of Murinae-associated hantaviruses and that adaptation has a role as well.",,"['Lin, Xian-Dan', 'Wang, Wen', 'Guo, Wen-Ping', 'Zhang, Xiao-He', 'Xing, Jian-Guang', 'Chen, Sheng-Ze', 'Li, Ming-Hui', 'Chen, Yi', 'Xu, Jianguo', 'Plyusnin, Alexander', 'Zhang, Yong-Zhen']",,,,
,PMC,Visualizing Production of Beta Interferon by Astrocytes and Microglia in Brain of La Crosse Virus-Infected Mice,http://dx.doi.org/10.1128/JVI.01093-12,PMC3457137,,,"Beta interferon (IFN-β) is a major component of innate immunity in mammals, but information on the in vivo source of this cytokine after pathogen infection is still scarce. To identify the cell types responsible for IFN-β production during viral encephalitis, we used reporter mice that express firefly luciferase under the control of the IFN-β promoter and stained organ sections with luciferase-specific antibodies. Numerous luciferase-positive cells were detected in regions of La Crosse virus (LACV)-infected mouse brains that contained many infected cells. Double-staining experiments with cell-type-specific markers revealed that similar numbers of astrocytes and microglia of infected brains were luciferase positive, whereas virus-infected neurons rarely contained detectable levels of luciferase. Interestingly, if a mutant LACV unable of synthesizing the IFN-antagonistic factor NSs was used for challenge, the vast majority of the IFN-β-producing cells in infected brains were astrocytes rather than microglia. Similar conclusions were reached in a second series of experiments in which conditional reporter mice expressing the luciferase reporter gene solely in defined cell types were infected with wild-type or mutant LACV. Collectively, our data suggest that glial cells rather than infected neurons represent the major source of IFN-β in LACV-infected mouse brains. They further indicate that IFN-β synthesis in astrocytes and microglia is differentially affected by the viral IFN antagonist, presumably due to differences in LACV susceptibility of these two cell types.",,"['Kallfass, Carsten', 'Ackerman, Andreas', 'Lienenklaus, Stefan', 'Weiss, Siegfried', 'Heimrich, Bernd', 'Staeheli, Peter']",,,,
,PMC,"Awareness and knowledge of disease surveillance and notification by health-care workers and availability of facility records in Anambra state, Nigeria",http://dx.doi.org/10.4103/0300-1652.107557,PMC3640243,23661882,CC BY-NC-SA,"BACKGROUND: Disease surveillance and notification (DSN) is part of the Health Management Information System (HMIS) which comprises databases, personnel, and materials that are organized to collect data which are utilized for informed decision making. The knowledge about DSN is very important for the reporting of notifiable diseases. OBJECTIVE: The aim of this study is to examine the awareness and knowledge of health-care workers about DSN, and availability of facility records in Anambra State, Nigeria. MATERIALS AND METHODS: The study was a descriptive cross-sectional one in which relevant data were collected from health-care workers selected by a multistage sampling technique. Qualitative information was also elicited by key informant interviews, whereas an observational checklist, preceded by a desk review was used to examine the availability of facility records. RESULTS: Although 89.8% of the health-care workers were aware of the DSN system, only 33.3, 31.1, and 33.7% of them knew the specific uses of forms IDSR 001, IDSR 002, and IDSR 003 (IDSR: Integrated Diseases Surveillance and Response), respectively. Knowledge of use of the various forms at the facility and local government area (LGA) levels were generally low, although the observational checklist revealed that IDSR 001 and IDSR 002 forms were predominantly found in primary health-care facilities. HMIS forms were less likely to be available in secondary health-care facilities (χ(2)=7.67, P=0.005). CONCLUSIONS: Regular training and retraining of concerned health-care workers on DSN at the LGA level is recommended. This should run concurrently with adequate and regular provision of IDSR forms, copies of the standard case definitions, and other necessary logistics to the health-care facilities by the local and state governments.",2012 Oct-Dec,"['Nnebue, Chinomnso C.', 'Onwasigwe, Chika N.', 'Adogu, Prosper O. U', 'Onyeonoro, Ugochukwu U.']",Niger Med J,,,
,PMC,Serum Proteome Changes in Dengue Virus-Infected Patients from a Dengue-Endemic Area of India: Towards New Molecular Targets?,http://dx.doi.org/10.1089/omi.2012.0037,PMC3459427,,,"The global burden of dengue continues to worsen, specifically in tropical and subtropical countries, and has evolved as a major public health problem. We investigated the changes in serum proteome in dengue fever (DF) patients from a dengue-endemic area of India to obtain mechanistic insights about the disease pathogenesis, the host immune response, and identification of potential serum protein biomarkers of this infectious disease. In this study, serum samples from DF patients, healthy subjects, and patients with falciparum malaria (an infectious disease control) were investigated by 2D-DIGE in combination with MALDI-TOF/TOF MS. The findings were validated with Western blotting. Functional clustering of the identified proteins was performed using PANTHER and DAVID tools. Compared to the healthy controls, we found significant changes in the expression levels of 48 protein spots corresponding to 18 unique proteins (7 downregulated and 11 upregulated) in DF patients (p<0.05). Among these differentially-expressed proteins, 11 candidates exhibited different trends in dengue fever compared to falciparum malaria. Importantly, our results suggest that dengue virus infection leads to alterations in expression levels of multiple serum proteins involved in diverse and vital physiological pathways, including acute phase response signaling, complement cascades, hemostasis, and blood coagulation. For the first time we report here that the serum levels of hemopexin, haptoglobin, serum amyloid P, and kininogen precursor, are altered in DF. This study informs the pathogenesis and host immune response to dengue virus infection, as well as the current search for new diagnostic and molecular drug targets.",,"['Ray, Sandipan', 'Srivastava, Rajneesh', 'Tripathi, Karnika', 'Vaibhav, Vineet', 'Patankar, Swati', 'Srivastava, Sanjeeva']",,,,
,PMC,Activation of Notch signaling during ex vivo expansion maintains donor muscle cell engraftment,http://dx.doi.org/10.1002/stem.1181,PMC3448880,,,"Transplantation of myogenic stem cells possesses great potential for long-term repair of dystrophic muscle. However, a single donor muscle biopsy is unlikely to provide enough cells to effectively transplant the muscle mass of a patient affected by muscular dystrophy. Expansion of cells ex vivo using traditional culture techniques significantly reduces engraftment potential. We hypothesized that activation of Notch signaling during ex vivo expansion would maintain donor cell engraftment potential. In this study, we expanded freshly isolated canine muscle-derived cells on tissue culture plates coated with Delta-1(ext)-IgG to activate Notch signaling or with human IgG as a control. A model of canine-to-murine xenotransplantation was used to quantitatively compare canine muscle cell engraftment, and determine if engrafted donor cells could function as satellite cells in vivo. We show that Delta-1(ext)-IgG inhibited differentiation of canine muscle-derived cells, and increased the level of genes normally expressed in myogenic precursors. Moreover, cells expanded on Delta-1(ext)-IgG resulted in a significant increase in the number of donor-derived fibers, as compared to cells expanded on human IgG, reaching engraftment levels similar to freshly isolated cells. Importantly, cells expanded on Delta-1(ext)-IgG engrafted to the recipient satellite cell niche, and contributed to further regeneration. A similar strategy of expanding human muscle-derived cells on Notch ligand might facilitate engraftment and muscle regeneration for patients affected with muscular dystrophy.",,"['Parker, Maura H.', 'Loretz, Carol', 'Tyler, Ashlee E.', 'Duddy, William J.', 'Hall, John K.', 'Olwin, Bradley B.', 'Bernstein, Irwin D.', 'Storb, Rainer', 'Tapscott, Stephen J.']",,,,
,PMC,Analysis of Human Monoclonal Antibodies Generated by Dengue Virus-Specific Memory B Cells,http://dx.doi.org/10.1089/vim.2012.0010,PMC3466914,,,"Dengue, caused by the four serotypes of dengue virus (DENV), represents an expanding global health challenge. The potential for serotype-cross-reactive antibodies to exacerbate disease during a secondary infection with a heterologous DENV serotype has driven efforts to study human DENV-specific antibodies. Most DENV-specific antibodies generated in humans are serotype-cross-reactive, weakly neutralizing, and directed against the immature pre-membrane (prM), envelope (E), and nonstructural 1 (NS1) proteins. To broaden the characterization of human DENV-specific antibodies, we assessed B-cell responses by ELISpot assays and isolated B cells from the peripheral blood of a human subject with previous DENV infection. Forty-eight human IgG monoclonal antibodies (hMAbs) were initially characterized by their potential to bind to an inactivated lysate of DENV-infected cells. Subsequently, most DENV-specific hMAbs were found to bind soluble, recombinant E protein (rE). Two hMAbs were unable to bind rE, despite strongly binding to the DENV-infected cell lysate. Further analyses showed that these two hMAbs bound conformation-dependent, reduction-sensitive epitopes on E protein. These data shed light on the breadth of DENV-specific hMAbs generated within a single immune donor.",,"['Friberg, Heather', 'Jaiswal, Smita', 'West, Kim', ""O'Ketch, Marvin"", 'Rothman, Alan L.', 'Mathew, Anuja']",,,,
,PMC,"Closing the gap: the challenges in converging theoretical, computational, experimental and real-life studies in virus evolution",http://dx.doi.org/10.1016/j.coviro.2012.09.008,PMC4096944,,,,,"['Vignuzzi, Marco', 'Andino, Raul']",,,,
,PMC,Segmentation with Area Constraints,http://dx.doi.org/10.1016/j.media.2012.09.002,PMC3656501,,,"Image segmentation approaches typically incorporate weak regularity conditions such as boundary length or curvature terms, or use shape information. High-level information such as a desired area or volume, or a particular topology are only implicitly specified. In this paper we develop a segmentation method with explicit bounds on the segmented area. Area constraints allow for the soft selection of meaningful solutions, and can counteract the shrinking bias of length-based regularization. We analyze the intrinsic problems of convex relaxations proposed in the literature for segmentation with size constraints. Hence, we formulate the area-constrained segmentation task as a mixed integer program, propose a branch and bound method for exact minimization, and use convex relaxations to obtain the required lower energy bounds on candidate solutions. We also provide a numerical scheme to solve the convex subproblems. We demonstrate the method for segmentations of vesicles from electron tomography images.",,"['Niethammer, Marc', 'Zach, Christopher']",,,,
,PMC,The Neck Region of the C-type Lectin DC-SIGN Regulates Its Surface Spatiotemporal Organization and Virus-binding Capacity on Antigen-presenting Cells,http://dx.doi.org/10.1074/jbc.M112.380121,PMC3493935,,,"The C-type lectin DC-SIGN expressed on dendritic cells (DCs) facilitates capture and internalization of a plethora of different pathogens. Although it is known that DC-SIGN organizes in nanoclusters at the surface of DCs, the molecular mechanisms responsible for this well defined nanopatterning and role in viral binding remain enigmatic. By combining biochemical and advanced biophysical techniques, including optical superresolution and single particle tracking, we demonstrate that DC-SIGN intrinsic nanoclustering strictly depends on its molecular structure. DC-SIGN nanoclusters exhibited free, Brownian diffusion on the cell membrane. Truncation of the extracellular neck region, known to abrogate tetramerization, significantly reduced nanoclustering and concomitantly increased lateral diffusion. Importantly, DC-SIGN nanocluster dissolution exclusively compromised binding to nanoscale size pathogens. Monte Carlo simulations revealed that heterogeneity on nanocluster density and spatial distribution confers broader binding capabilities to DC-SIGN. As such, our results underscore a direct relationship between spatial nanopatterning, driven by intermolecular interactions between the neck regions, and receptor diffusion to provide DC-SIGN with the exquisite ability to dock pathogens at the virus length scale. Insight into how virus receptors are organized prior to virus binding and how they assemble into functional platforms for virus docking is helpful to develop novel strategies to prevent virus entry and infection.",,"['Manzo, Carlo', 'Torreno-Pina, Juan A.', 'Joosten, Ben', 'Reinieren-Beeren, Inge', 'Gualda, Emilio J.', 'Loza-Alvarez, Pablo', 'Figdor, Carl G.', 'Garcia-Parajo, Maria F.', 'Cambi, Alessandra']",,,,
,PMC,Structural and functional insights into alphavirus polyprotein processing and pathogenesis,http://dx.doi.org/10.1073/pnas.1210418109,PMC3478664,,,"Alphaviruses, a group of positive-sense RNA viruses, are globally distributed arboviruses capable of causing rash, arthritis, encephalitis, and death in humans. The viral replication machinery consists of four nonstructural proteins (nsP1–4) produced as a single polyprotein. Processing of the polyprotein occurs in a highly regulated manner, with cleavage at the P2/3 junction influencing RNA template use during genome replication. Here, we report the structure of P23 in a precleavage form. The proteins form an extensive interface and nsP3 creates a ring structure that encircles nsP2. The P2/3 cleavage site is located at the base of a narrow cleft and is not readily accessible, suggesting a highly regulated cleavage. The nsP2 protease active site is over 40 Å away from the P2/3 cleavage site, supporting a trans cleavage mechanism. nsP3 contains a previously uncharacterized protein fold with a zinc-coordination site. Known mutations in nsP2 that result in formation of noncytopathic viruses or a temperature sensitive phenotype cluster at the nsP2/nsP3 interface. Structure-based mutations in nsP3 opposite the location of the nsP2 noncytopathic mutations prevent efficient cleavage of P23, affect RNA infectivity, and alter viral RNA production levels, highlighting the importance of the nsP2/nsP3 interaction in pathogenesis. A potential RNA-binding surface, spanning both nsP2 and nsP3, is proposed based on the location of ion-binding sites and adaptive mutations. These results offer unexpected insights into viral protein processing and pathogenesis that may be applicable to other polyprotein-encoding viruses such as HIV, hepatitis C virus (HCV), and Dengue virus.",,"['Shin, Gyehwa', 'Yost, Samantha A.', 'Miller, Matthew T.', 'Elrod, Elizabeth J.', 'Grakoui, Arash', 'Marcotrigiano, Joseph']",,,,
,PMC,Virus nomenclature below the species level: a standardized nomenclature for natural variants of viruses assigned to the family Filoviridae,http://dx.doi.org/10.1007/s00705-012-1454-0,PMC3535543,,,"The task of international expert groups is to recommend the classification and naming of viruses. The ICTV Filoviridae Study Group and other experts have recently established an almost consistent classification and nomenclature for filoviruses. Here, further guidelines are suggested to include their natural genetic variants. First, this term is defined. Second, a template for full-length virus names (such as “Ebola virus H.sapiens-tc/COD/1995/Kikwit-9510621”) is proposed. These names contain information on the identity of the virus (e.g., Ebola virus), isolation host (e.g., members of the species Homo sapiens), sampling location (e.g., Democratic Republic of the Congo (COD)), sampling year, genetic variant (e.g., Kikwit), and isolate (e.g., 9510621). Suffixes are proposed for individual names that clarify whether a given genetic variant has been characterized based on passage zero material (-wt), has been passaged in tissue/cell culture (-tc), is known from consensus sequence fragments only (-frag), or does (most likely) not exist anymore (-hist). We suggest that these comprehensive names are to be used specifically in the methods section of publications. Suitable abbreviations, also proposed here, could then be used throughout the text, while the full names could be used again in phylograms, tables, or figures if the contained information aids the interpretation of presented data. The proposed system is very similar to the well-known influenzavirus nomenclature and the nomenclature recently proposed for rotaviruses. If applied consistently, it would considerably simplify retrieval of sequence data from electronic databases and be a first important step toward a viral genome annotation standard as sought by the National Center for Biotechnology Information (NCBI). Furthermore, adoption of this nomenclature would increase the general understanding of filovirus-related publications and presentations and improve figures such as phylograms, alignments, and diagrams. Most importantly, it would counter the increasing confusion in genetic variant naming due to the identification of ever more sequences through technological breakthroughs in high-throughput sequencing and environmental sampling.",,"['Kuhn, Jens H.', 'Bao, Yiming', 'Bavari, Sina', 'Becker, Stephan', 'Bradfute, Steven', 'Brister, J. Rodney', 'Bukreyev, Alexander A.', 'Chandran, Kartik', 'Davey, Robert A.', 'Dolnik, Olga', 'Dye, John M.', 'Enterlein, Sven', 'Hensley, Lisa', 'Honko, Anna N.', 'Jahrling, Peter B.', 'Johnson, Karl M.', 'Kobinger, Gary', 'Leroy, Eric M.', 'Lever, Mark S.', 'Mühlberger, Elke', 'Netesov, Sergey V.', 'Olinger, Gene G.', 'Palacios, Gustavo', 'Patterson, Jean L.', 'Paweska, Janusz T.', 'Pitt, Louise', 'Radoshitzky, Sheli R.', 'Saphire, Erica Ollmann', 'Smither, Sophie J.', 'Swanepoel, Robert', 'Towner, Jonathan S.', 'van der Groen, Guido', 'Volchkov, Viktor E.', 'Wahl-Jensen, Victoria', 'Warren, Travis', 'Weidmann, Manfred', 'Nichol, Stuart T.']",,,,
,PMC,The essential adaptors of innate immune signaling,http://dx.doi.org/10.1007/s13238-012-2063-0,PMC4875439,,,"Microbial components and the endogenous molecules released from damaged cells can stimulate germ-line-encoded pattern recognition receptors (PRRs) to transduce signals to the hub of the innate immune signaling network-the adaptor proteins MyD88/TRIF/MAVS/STING/Caspase-1, where integrated signals relay to the relevant transcription factors IRF3/IRF7/NF-κB/ AP-1 and the signal transducer and activator of transcription 6 (STAT6) to trigger the expression of type I interferons and inflammatory cytokines or the assembly of inflammasomes. Most pleiotropic cytokines are secreted and bind to specific receptors, activating the signaling pathways including JAK-STAT for the proliferation, differentiation and functional capacity of immune cells. This review focuses on several critical adaptors in innate immune signaling cascades and recent progress in their molecular mechanisms.",,"['Chen, Huihui', 'Jiang, Zhengfan']",,,,
,PMC,"Unconsented HIV Testing in Cases of Occupational Exposure: Ethics, Law, and Policy",http://dx.doi.org/10.1111/j.1553-2712.2012.01453.x,PMC3473147,,,"Post-exposure prophylaxis (PEP) has substantially reduced the risk of acquiring human immunodeficiency virus (HIV) after an occupational exposure; nevertheless, exposure to HIV remains a concern for emergency department providers. According to published guidelines, PEP should be taken only when source patients are HIV positive or have risk factors for HIV. Initiating PEP when source patients are uninfected puts exposed persons at risk from taking toxic drugs with no compensating benefit. Forgoing PEP if the source is infected results in increased risk of acquiring HIV. What should be done if source patients refuse HIV testing? Is it justifiable to test the blood of these patients over their autonomous objection? The authors review current law and policy and perform an ethical analysis to determine if laws permitting unconsented testing in cases of occupational exposure can be ethically justified.",,"['Cowan, Ethan', 'Macklin, Ruth']",,,,
,PMC,Plant-derived virus-like particles as vaccines,http://dx.doi.org/10.4161/hv.22218,PMC3667944,,,"Virus-like particles (VLPs) are self-assembled structures derived from viral antigens that mimic the native architecture of viruses but lack the viral genome. VLPs have emerged as a premier vaccine platform due to their advantages in safety, immunogenicity, and manufacturing. The particulate nature and high-density presentation of viral structure proteins on their surface also render VLPs as attractive carriers for displaying foreign epitopes. Consequently, several VLP-based vaccines have been licensed for human use and achieved significant clinical and economical success. The major challenge, however, is to develop novel production platforms that can deliver VLP-based vaccines while significantly reducing production times and costs. Therefore, this review focuses on the essential role of plants as a novel, speedy and economical production platform for VLP-based vaccines. The advantages of plant expression systems are discussed in light of their distinctive posttranslational modifications, cost-effectiveness, production speed, and scalability. Recent achievements in the expression and assembly of VLPs and their chimeric derivatives in plant systems as well as their immunogenicity in animal models are presented. Results of human clinical trials demonstrating the safety and efficacy of plant-derived VLPs are also detailed. Moreover, the promising implications of the recent creation of “humanized” glycosylation plant lines as well as the very recent approval of the first plant-made biologics by the U. S. Food and Drug Administration (FDA) for plant production and commercialization of VLP-based vaccines are discussed. It is speculated that the combined potential of plant expression systems and VLP technology will lead to the emergence of successful vaccines and novel applications of VLPs in the near future.",,"['Chen, Qiang', 'Lai, Huafang']",,,,
,PMC,Crystal Structure of the Marburg Virus GP2 Core Domain in its Post-Fusion Conformation,http://dx.doi.org/10.1021/bi300976m,PMC3464016,,,"Marburg virus (MARV) and Ebola virus (EBOV) are members of the family Filoviridae (‘filoviruses’) that cause severe hemorrhagic fever with human case fatality rates of up to 90%. Filovirus infection requires fusion of the host cell and virus membranes, a process that is mediated by the envelope glycoprotein (GP). GP contains two subunits, the surface subunit (GP1), which is responsible for cell attachment, and the transmembrane subunit (GP2), which catalyzes membrane fusion. The GP2 ectodomain contains two heptad repeat regions, N-terminal and C-terminal (NHR and CHR, respectively) that adopt a six-helix bundle during the fusion process. The refolding of this six-helix bundle provides the thermodynamic driving force to overcome barriers associated with membrane fusion. Here we report the crystal structure of the MARV GP2 core domain in its post-fusion (six-helix bundle) conformation at 1.9 Å resolution. The MARV GP2 core domain backbone conformation is virtually identical to that of EBOV GP2 (reported previously), and consists of a central NHR core trimeric coiled-coil packed against peripheral CHR α-helices and an intervening loop/helix-turn-helix segment. We previously reported that the stability of the MARV GP2 post-fusion structure is highly pH-dependent, with increasing stability at lower pH [Harrison, J.S.; Koellhoffer, J. K.; Chandran, K.; and Lai, J. R. Biochemistry, 2012, 51, 2515–2525]. We hypothesized that this pH-dependent stability provides a mechanism for conformational control such that the post-fusion six helix bundle is promoted in the environments of appropriately matured endosomes. In this report, a structural rationale for this pH-dependent stability is described, and involves a high-density array of core and surface acidic side chains at the midsection of the structure, termed the ‘anion stripe.’ In addition, many surface-exposed salt bridges likely contribute to stabilizing the post-fusion structure at low pH. These results provide structural insights into the mechanism of MARV GP2-mediated membrane fusion.",,"['Koellhoffer, Jayne F.', 'Malashkevich, Vladimir N.', 'Harrison, Joseph S.', 'Toro, Rafael', 'Bhosle, Rahul C.', 'Chandran, Kartik', 'Almo, Steven C.', 'Lai, Jonathan R.']",,,,
,PMC,"Programmed −1 frameshifting efficiency correlates with RNA pseudoknot conformational plasticity, not resistance to mechanical unfolding",http://dx.doi.org/10.1073/pnas.1204114109,PMC3479558,,,"Programmed −1 frameshifting, whereby the reading frame of a ribosome on messenger RNA is shifted in order to generate an alternate gene product, is often triggered by a pseudoknot structure in the mRNA in combination with an upstream slippery sequence. The efficiency of frameshifting varies widely for different sites, but the factors that determine frameshifting efficiency are not yet fully understood. Previous work has suggested that frameshifting efficiency is related to the resistance of the pseudoknot against mechanical unfolding. We tested this hypothesis by studying the mechanical properties of a panel of pseudoknots with frameshifting efficiencies ranging from 2% to 30%: four pseudoknots from retroviruses, two from luteoviruses, one from a coronavirus, and a nonframeshifting bacteriophage pseudoknot. Using optical tweezers to apply tension across the RNA, we measured the distribution of forces required to unfold each pseudoknot. We found that neither the average unfolding force, nor the unfolding kinetics, nor the parameters describing the energy landscape for mechanical unfolding of the pseudoknot (energy barrier height and distance to the transition state) could be correlated to frameshifting efficiency. These results indicate that the resistance of pseudoknots to mechanical unfolding is not a primary determinant of frameshifting efficiency. However, increased frameshifting efficiency was correlated with an increased tendency to form alternate, incompletely folded structures, suggesting a more complex picture of the role of the pseudoknot involving the conformational dynamics.",,"['Ritchie, Dustin B.', 'Foster, Daniel A. N.', 'Woodside, Michael T.']",,,,
,PMC,In-Flight Medical Emergencies,http://dx.doi.org/10.3238/arztebl.2012.0591,PMC3461894,,,"BACKGROUND: One in every 10 000 to 40 000 passengers on commercial aircraft will have a medical incident while on board. Many physicians are unaware of the special features of the cabin atmosphere, the medical equipment available on airplanes, and the resulting opportunities for medical intervention. METHODS: A selective literature search was performed and supplemented with international recommendations and guidelines and with data from the Lufthansa registry. RESULTS: Data on in-flight medical emergencies have been collected in various ways, with varying results; it is generally agreed, however, that the more common incidents include gastrointestinal conditions (diarrhea, nausea, vomiting), circulatory collapse, hypertension, stroke, and headache (including migraine). Data from the Lufthansa registry for the years 2010 and 2011 reveal the rarity of cardiopulmonary resuscitation (mean: 8 cases per year), death (12 cases per year), childbirth (1 case per year), and psychiatric incidents (81 cases per year). If one assumes that one medical incident arises for every 10 000 passengers, and that there are 400 passengers on board each flight, then one can calculate that the probability of experiencing at least one medical incident reaches 95% after 24 intercontinental flights. CONCLUSION: An in-flight medical emergency is an exceptional event for the physician and all other persons involved. Physician passengers can act more effectively if they are aware of the framework conditions, the available medical equipment, and the commonly encountered medical conditions.",,"['Graf, Jürgen', 'Stüben, Uwe', 'Pump, Stefan']",,,,
,PMC,Detection of Respiratory Viruses in Asymptomatic Children Undergoing Allogeneic Hematopoietic Cell Transplantation,http://dx.doi.org/10.1002/pbc.24314,PMC3502722,,,"Detection of respiratory viruses by molecular methods, in children without respiratory symptoms undergoing hematopoietic cell transplantation (HCT), has not been well described. A prospective study of 33 asymptomatic children detected respiratory viruses in 8 of 33 (24%) patients before HCT. Human rhinovirus (HRV) was detected in 5 patients, and human adenovirus (hADV) in 3 patients. Two additional patients shed HRV, and one shed human coronavirus (hCoV), post-HCT. Two patients had co-infections. Of the 11 asymptomatic patients where respiratory virus was detected, 3 (27%) later developed an upper respiratory tract infection, from the same virus.",,"['Srinivasan, Ashok', 'Flynn, Patricia', 'Gu, Zhengming', 'Hartford, Christine', 'Lovins, Richard', 'Sunkara, Anusha', 'Srivastava, Deo K.', 'Leung, Wing', 'Hayden, Randall T.']",,,,
,PMC,Poster Sessions,http://dx.doi.org/10.1111/imm.12002,PMC3458242,,,,,,,,,
,PMC,The influence of virus infections on the course of COPD,http://dx.doi.org/10.1556/EuJMI.2.2012.3.2,PMC3962752,,,"Chronic obstructive pulmonary disease (COPD) is extensively influenced by viral infections. The mechanisms of how viral agents affect the pathogenesis and prognosis of COPD are numerous. In general, patients with infectious exacerbations are characterized by longer hospitalization periods and greater impairment of several lung function parameters than those with non-infectious exacerbations. Prodromal, clinical, and outcome parameters fail to distinguish virally from non-virally induced illnesses in cases of exacerbations. The importance of infections with respiratory and non-respiratory viral agents for pathogenesis and course of COPD is detailed. Human adenovirus, non-respiratory viruses including human immunodeficiency virus, human metapneumovirus, influenza virus, human rhinovirus, and respiratory syncytial virus are especially stressed.",,"['Frickmann, H.', 'Jungblut, S.', 'Hirche, T. O.', 'Groß, U.', 'Kuhns, M.', 'Zautner, A. E.']",,,,
,PMC,Spectrum of viral infections in patients with cystic fibrosis,http://dx.doi.org/10.1556/EuJMI.2.2012.3.1,PMC3962751,,,"This review explores the extensive influence of viral infections leading to chronic deterioration of lung function in patients with cystic fibrosis (CF). The mechanisms how viral agents affect the pathogenesis as well as the inflammatory and immune response of CF are discussed. Viral infections of the upper and lower respiratory tract due to viruses in CF patients and methods for diagnosis of respiratory viruses are described in detail. The importance of respiratory and non-respiratory viral agents for the pathogenesis, especially for the exacerbation of bacterial lower respiratory tract infections and course of CF, is stressed, especially emphasizing respiratory syncytial virus, influenza virus, rhinovirus, and human herpes viruses. Possible harmful effects of further viruses like adenovirus, bocavirus, coronavirus, metapneumovirus, parainfluenzavirus on the lung function of CF patients are discussed. The potential use of adenovirus-based vectors for somatic gene therapy is mentioned.",,"['Frickmann, H.', 'Jungblut, S.', 'Hirche, T. O.', 'Groß, U.', 'Kuhns, M.', 'Zautner, A. E.']",,,,
,PMC,Structure of the cleavage-activated prefusion form of the parainfluenza virus 5 fusion protein,http://dx.doi.org/10.1073/pnas.1213802109,PMC3478641,,,"The paramyxovirus parainfluenza virus 5 (PIV5) enters cells by fusion of the viral envelope with the plasma membrane through the concerted action of the fusion (F) protein and the receptor binding protein hemagglutinin-neuraminidase. The F protein folds initially to form a trimeric metastable prefusion form that is triggered to undergo large-scale irreversible conformational changes to form the trimeric postfusion conformation. It is thought that F refolding couples the energy released with membrane fusion. The F protein is synthesized as a precursor (F0) that must be cleaved by a host protease to form a biologically active molecule, F1,F2. Cleavage of F protein is a prerequisite for fusion and virus infectivity. Cleavage creates a new N terminus on F1 that contains a hydrophobic region, known as the FP, which intercalates target membranes during F protein refolding. The crystal structure of the soluble ectodomain of the uncleaved form of PIV5 F is known; here we report the crystal structure of the cleavage-activated prefusion form of PIV5 F. The structure shows minimal movement of the residues adjacent to the protease cleavage site. Most of the hydrophobic FP residues are buried in the uncleaved F protein, and only F103 at the newly created N terminus becomes more solvent-accessible after cleavage. The conformational freedom of the charged arginine residues that compose the protease recognition site increases on cleavage of F protein.",,"['Welch, Brett D.', 'Liu, Yuanyuan', 'Kors, Christopher A.', 'Leser, George P.', 'Jardetzky, Theodore S.', 'Lamb, Robert A.']",,,,
,PMC,The future of human DNA vaccines,http://dx.doi.org/10.1016/j.jbiotec.2012.08.012,PMC3511659,,,"DNA vaccines have evolved greatly over the last 20 years since their invention, but have yet to become a competitive alternative to conventional protein or carbohydrate based human vaccines. Whilst safety concerns were an initial barrier, the Achilles heel of DNA vaccines remains their poor immunogenicity when compared to protein vaccines. A wide variety of strategies have been developed to optimize DNA vaccine immunogenicity, including codon optimization, genetic adjuvants, electroporation and sophisticated prime-boost regimens, with each of these methods having its advantages and limitations. Whilst each of these methods has contributed to incremental improvements in DNA vaccine efficacy, more is still needed if human DNA vaccines are to succeed commercially. This review foresees a final breakthrough in human DNA vaccines will come from application of the latest cutting-edge technologies, including “epigenetics” and “omics” approaches, alongside traditional techniques to improve immunogenicity such as adjuvants and electroporation, thereby overcoming the current limitations of DNA vaccines in humans",,"['Li, Lei', 'Saade, Fadi', 'Petrovsky, Nikolai']",,,,
,PMC,T-bet(+) Treg Cells Undergo Abortive Th1 Cell Differentiation due to Impaired Expression of IL-12 Receptor β2,http://dx.doi.org/10.1016/j.immuni.2012.05.031,PMC3501343,,,"Foxp3(+) regulatory T (Treg) cells limit inflammatory responses and maintain immune homeostasis. Although comprised of several phenotypically and functionally distinct subsets, the differentiation of specialized Treg cell populations within the periphery is poorly characterized. We demonstrate that the development of T-bet(+) Treg cells that potently inhibit T helper (Th)1 cell responses was dependent on the transcription factor STAT1, and occurred directly in response to interferon-γ produced by effector T cells. Additionally, delayed induction of the IL-12Rβ2 receptor component following STAT1 activation helped ensure that Treg cells do not readily complete STAT4-dependent Th1 cell development and lose their ability to suppress effector T cell proliferation. Thus, we define a pathway of abortive Th1 cell development that results in the specialization of peripheral Treg cells, and demonstrate that impaired expression of a single cytokine receptor helps maintain Treg cell suppressive function in the context of inflammatory Th1 cell responses.",,"['Koch, Meghan A.', 'Thomas, Kerri N.', 'Perdue, Nikole R.', 'Smigiel, Kate S.', 'Srivastava, Shivani', 'Campbell, Daniel J.']",,,,
,PMC,Detection of Nipah Virus RNA in Fruit Bat (Pteropus giganteus) from India,http://dx.doi.org/10.4269/ajtmh.2012.11-0416,PMC3435367,,,"The study deals with the survey of different bat populations (Pteropus giganteus, Cynopterus sphinx, and Megaderma lyra) in India for highly pathogenic Nipah virus (NiV), Reston Ebola virus, and Marburg virus. Bats (n = 140) from two states in India (Maharashtra and West Bengal) were tested for IgG (serum samples) against these viruses and for virus RNAs. Only NiV RNA was detected in a liver homogenate of P. giganteus captured in Myanaguri, West Bengal. Partial sequence analysis of nucleocapsid, glycoprotein, fusion, and phosphoprotein genes showed similarity with the NiV sequences from earlier outbreaks in India. A serum sample of this bat was also positive by enzyme-linked immunosorbent assay for NiV-specific IgG. This is the first report on confirmation of Nipah viral RNA in Pteropus bat from India and suggests the possible role of this species in transmission of NiV in India.",,"['Yadav, Pragya D.', 'Raut, Chandrashekhar G.', 'Shete, Anita M.', 'Mishra, Akhilesh C.', 'Towner, Jonathan S.', 'Nichol, Stuart T.', 'Mourya, Devendra T.']",,,,
,PMC,Grb14 Is a Negative Regulator of CEACAM3-mediated Phagocytosis of Pathogenic Bacteria,http://dx.doi.org/10.1074/jbc.M112.395228,PMC3493956,,,"Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3) is a phagocytic receptor on human granulocytes, which mediates the opsonin-independent recognition and internalization of a restricted set of Gram-negative bacteria such as Neisseria gonorrhoeae. In an unbiased screen using a SH2 domain microarray we identified the SH2 domain of growth factor receptor-bound protein 14 (Grb14) as a novel binding partner of CEACAM3. Biochemical assays and microscopic studies demonstrated that the Grb14 SH2 domain promoted the rapid recruitment of this adaptor protein to the immunoreceptor-based activation motif (ITAM)-like sequence within the cytoplasmic domain of CEACAM3. Furthermore, FRET-FLIM analyses confirmed the direct association of Grb14 and CEACAM3 in intact cells at the sites of bacteria-host cell contact. Knockdown of endogenous Grb14 by RNA interference as well as Grb14 overexpression indicate an inhibitory role for this adapter protein in CEACAM3-mediated phagocytosis. Therefore, Grb14 is the first negative regulator of CEACAM3-initiated bacterial phagocytosis and might help to focus granulocyte responses to the subcellular sites of pathogen-host cell contact.",,"['Kopp, Kathrin', 'Buntru, Alexander', 'Pils, Stefan', 'Zimmermann, Timo', 'Frank, Ronald', 'Zumbusch, Andreas', 'Hauck, Christof R.']",,,,
,PMC,TRIM56 Is an Essential Component of the TLR3 Antiviral Signaling Pathway,http://dx.doi.org/10.1074/jbc.M112.397075,PMC3476306,,,"Members of the tripartite motif (TRIM) proteins are being recognized as important regulators of host innate immunity. However, specific TRIMs that contribute to TLR3-mediated antiviral defense have not been identified. We show here that TRIM56 is a positive regulator of TLR3 signaling. Overexpression of TRIM56 substantially potentiated extracellular dsRNA-induced expression of interferon (IFN)-β and interferon-stimulated genes (ISGs), while knockdown of TRIM56 greatly impaired activation of IRF3, induction of IFN-β and ISGs, and establishment of an antiviral state by TLR3 ligand and severely compromised TLR3-mediated chemokine induction following infection by hepatitis C virus. The ability to promote TLR3 signaling was independent of the E3 ubiquitin ligase activity of TRIM56. Rather, it correlated with a physical interaction between TRIM56 and TRIF. Deletion of the C-terminal portion of TRIM56 abrogated the TRIM56-TRIF interaction as well as the augmentation of TLR3-mediated IFN response. Together, our data demonstrate TRIM56 is an essential component of the TLR3 antiviral signaling pathway and reveal a novel role for TRIM56 in innate antiviral immunity.",,"['Shen, Yang', 'Li, Nan L.', 'Wang, Jie', 'Liu, Baoming', 'Lester, Sandra', 'Li, Kui']",,,,
,PMC,Pemphigus autoantibodies generated through somatic mutations target the desmoglein-3 cis-interface,http://dx.doi.org/10.1172/JCI64413,PMC3461925,,,"Pemphigus vulgaris (PV) is an autoimmune blistering disease of skin and mucous membranes caused by autoantibodies to the desmoglein (DSG) family proteins DSG3 and DSG1, leading to loss of keratinocyte cell adhesion. To learn more about pathogenic PV autoantibodies, we isolated 15 IgG antibodies specific for DSG3 from 2 PV patients. Three antibodies disrupted keratinocyte monolayers in vitro, and 2 were pathogenic in a passive transfer model in neonatal mice. The epitopes recognized by the pathogenic antibodies were mapped to the DSG3 extracellular 1 (EC1) and EC2 subdomains, regions involved in cis-adhesive interactions. Using a site-specific serological assay, we found that the cis-adhesive interface on EC1 recognized by the pathogenic antibody PVA224 is the primary target of the autoantibodies present in the serum of PV patients. The autoantibodies isolated used different heavy- and light-chain variable region genes and carried high levels of somatic mutations in complementary-determining regions, consistent with antigenic selection. Remarkably, binding to DSG3 was lost when somatic mutations were reverted to the germline sequence. These findings identify the cis-adhesive interface of DSG3 as the immunodominant region targeted by pathogenic antibodies in PV and indicate that autoreactivity relies on somatic mutations generated in the response to an antigen unrelated to DSG3.",,"['Di Zenzo, Giovanni', 'Di Lullo, Giulia', 'Corti, Davide', 'Calabresi, Valentina', 'Sinistro, Anna', 'Vanzetta, Fabrizia', 'Didona, Biagio', 'Cianchini, Giuseppe', 'Hertl, Michael', 'Eming, Rudiger', 'Amagai, Masayuki', 'Ohyama, Bungo', 'Hashimoto, Takashi', 'Sloostra, Jerry', 'Sallusto, Federica', 'Zambruno, Giovanna', 'Lanzavecchia, Antonio']",,,,
,PMC,"Development of Anti-Infectives Using Phage Display: Biological Agents against Bacteria, Viruses, and Parasites",http://dx.doi.org/10.1128/AAC.00567-12,PMC3421897,,,"The vast majority of anti-infective therapeutics on the market or in development are small molecules; however, there is now a nascent pipeline of biological agents in development. Until recently, phage display technologies were used mainly to produce monoclonal antibodies (MAbs) targeted against cancer or inflammatory disease targets. Patent disputes impeded broad use of these methods and contributed to the dearth of candidates in the clinic during the 1990s. Today, however, phage display is recognized as a powerful tool for selecting novel peptides and antibodies that can bind to a wide range of antigens, ranging from whole cells to proteins and lipid targets. In this review, we highlight research that exploits phage display technology as a means of discovering novel therapeutics against infectious diseases, with a focus on antimicrobial peptides and antibodies in clinical or preclinical development. We discuss the different strategies and methods used to derive, select, and develop anti-infectives from phage display libraries and then highlight case studies of drug candidates in the process of development and commercialization. Advances in screening, manufacturing, and humanization technologies now mean that phage display can make a significant contribution in the fight against clinically important pathogens.",,"['Huang, Johnny X.', 'Bishop-Hurley, Sharon L.', 'Cooper, Matthew A.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Replication Inhibitor That Interferes with the Nucleic Acid Unwinding of the Viral Helicase,http://dx.doi.org/10.1128/AAC.00957-12,PMC3421890,,,"Severe acute respiratory syndrome (SARS) is a highly contagious disease, caused by SARS coronavirus (SARS-CoV), for which there are no approved treatments. We report the discovery of a potent inhibitor of SARS-CoV that blocks replication by inhibiting the unwinding activity of the SARS-CoV helicase (nsp13). We used a Förster resonance energy transfer (FRET)-based helicase assay to screen the Maybridge Hitfinder chemical library. We identified and validated a compound (SSYA10-001) that specifically blocks the double-stranded RNA (dsRNA) and dsDNA unwinding activities of nsp13, with 50% inhibitory concentrations (IC(50)s) of 5.70 and 5.30 μM, respectively. This compound also has inhibitory activity (50% effective concentration [EC(50)] = 8.95 μM) in a SARS-CoV replicon assay, with low cytotoxicity (50% cytotoxic concentration [CC(50)] = >250 μM), suggesting that the helicase plays a still unidentified critical role in the SARS-CoV life cycle. Enzyme kinetic studies on the mechanism of nsp13 inhibition revealed that SSYA10-001 acts as a noncompetitive inhibitor of nsp13 with respect to nucleic acid and ATP substrates. Moreover, SSYA10-001 does not affect ATP hydrolysis or nsp13 binding to the nucleic acid substrate. SSYA10-001 did not inhibit hepatitis C virus (HCV) helicase, other bacterial and viral RNA-dependent RNA polymerases, or reverse transcriptase. These results suggest that SSYA10-001 specifically blocks nsp13 through a novel mechanism and is less likely to interfere with the functions of cellular enzymes that process nucleic acids or ATP. Hence, it is possible that SSYA10-001 inhibits unwinding by nsp13 by affecting conformational changes during the course of the reaction or translocation on the nucleic acid. SSYA10-001 will be a valuable tool for studying the specific role of nsp13 in the SARS-CoV life cycle, which could be a model for other nidoviruses and also a candidate for further development as a SARS antiviral target.",,"['Adedeji, Adeyemi O.', 'Singh, Kamalendra', 'Calcaterra, Nicholas E.', 'DeDiego, Marta L.', 'Enjuanes, Luis', 'Weiss, Susan', 'Sarafianos, Stefan G.']",,,,
,PMC,Quantification of Diatom Gene Expression in the Sea by Selecting Uniformly Transcribed mRNA as the Basis for Normalization,http://dx.doi.org/10.1128/AEM.00935-12,PMC3416636,,,"To quantify gene expressions by quantitative reverse transcription-PCR (Q-RT-PCR) in natural diatom assemblages, it is necessary to seek a biomass reference specific to the target species. Two housekeeping genes, TBP (encoding the TATA box-binding protein) and EFL (encoding the translation elongation factor-like protein), were evaluated as candidates for reference genes in Q-RT-PCR assays. Transcript levels of TBP and EFL were relatively stable under various test conditions including growth stages, light-dark cycle phases, and nutrient stresses in Skeletonema costatum and Chaetoceros affinis, and TBP expression was more stable than that of EFL. Next, the sequence diversity of diatom assemblages was evaluated by obtaining 32 EFL and 29 TBP homologous gene fragments from the East China Sea (ECS). Based on sequence alignments, EFL and TBP primer sets were designed for Chaetoceros and Skeletonema groups in the ECS. An evaluation of primer specificity and PCR efficiency indicated that the EFL primer sets performed better. To demonstrate the applicability of EFL primer sets in the ECS, they were employed to measure mRNA levels of the FcpB (fucoxanthin-chlorophyll protein) gene in diatoms. The results correctly revealed prominent diel variations in FcpB expression and confirmed EFL as a good reference gene.",,"['Kang, Lee-Kuo', 'Tsui, Feng-Hsiu', 'Chang, Jeng']",,,,
,PMC,Cytosolic clearance of replication-deficient mutants reveals Francisella tularensis interactions with the autophagic pathway,http://dx.doi.org/10.4161/auto.20808,PMC3442881,,,"Cytosolic bacterial pathogens must evade intracellular innate immune recognition and clearance systems such as autophagy to ensure their survival and proliferation. The intracellular cycle of the bacterium Francisella tularensis is characterized by rapid phagosomal escape followed by extensive proliferation in the macrophage cytoplasm. Cytosolic replication, but not phagosomal escape, requires the locus FTT0369c, which encodes the dipA gene (deficient in intracellular replication A). Here, we show that a replication-deficient, ∆dipA mutant of the prototypical SchuS4 strain is eventually captured from the cytosol of murine and human macrophages into double-membrane vacuoles displaying the late endosomal marker, LAMP1, and the autophagy-associated protein, LC3, coinciding with a reduction in viable intracellular bacteria. Capture of SchuS4ΔdipA was not dipA-specific as other replication-deficient bacteria, such as chloramphenicol-treated SchuS4 and a purine auxotroph mutant SchuS4ΔpurMCD, were similarly targeted to autophagic vacuoles. Vacuoles containing replication-deficient bacteria were labeled with ubiquitin and the autophagy receptors SQSTM1/p62 and NBR1, and their formation was decreased in macrophages from either ATG5-, LC3B- or SQSTM1-deficient mice, indicating recognition by the ubiquitin-SQSTM1-LC3 pathway. While a fraction of both the wild-type and the replication-impaired strains were ubiquitinated and recruited SQSTM1, only the replication-defective strains progressed to autophagic capture, suggesting that wild-type Francisella interferes with the autophagic cascade. Survival of replication-deficient strains was not restored in autophagy-deficient macrophages, as these bacteria died in the cytosol prior to autophagic capture. Collectively, our results demonstrate that replication-impaired strains of Francisella are cleared by autophagy, while replication-competent bacteria seem to interfere with autophagic recognition, therefore ensuring survival and proliferation.",,"['Chong, Audrey', 'Wehrly, Tara D.', 'Child, Robert', 'Hansen, Bryan', 'Hwang, Seungmin', 'Virgin, Herbert W.', 'Celli, Jean']",,,,
,PMC,Physical Interventions to Interrupt or Reduce the Spread of Respiratory Viruses — Resource Use Implications: A Systematic Review,,PMC3442616,,,,,"['Lee, KM', 'Shukla, VK', 'Clark, M', 'Mierzwinski-Urban, M', 'Pessoa-Silva, CL', 'Conly, J']",,,,
,PMC,Restrictive Measures in an Influenza Pandemic: A Qualitative Study of Public Perspectives,http://dx.doi.org/10.1007/BF03404439,PMC6973992,,,"OBJECTIVES: Recent experiences have demonstrated that restrictive measures remain a useful public health tool during infectious disease outbreaks. However, the use of restrictive measures is not without controversy, as there is no agreed-upon threshold for when and how to invoke restrictive measures. The objectives of this study are to solicit perspectives from Canadians on the ethical considerations of using restrictive measures in response to influenza pandemics, and in turn, to use public views to contribute to a better understanding of what is considered to be the justifiable use of restrictive measures. METHODS: A series of town hall focus groups with Canadian residents from June 2008 to May 2009, in three Canadian regions, in order to achieve broad public engagement (n=3 focus groups with a total of 17 participants). RESULTS: Two key themes emerged from all town hall focus groups: 1) create an environment for compliance through communication rather than enforcement, and 2) establish the delineation between individual rights, community values, and the greater good. CONCLUSION: While there is a need for a decision-making authority and even a mechanism for enforcement, our data suggest that a more tractable approach to restrictive measures is one that enables individuals to voluntarily comply by creating an environment to compel compliance based on communication. This approach requires restrictive measures to be a) proportional to the threat, b) implemented along with reciprocal arrangements provided to those affected, and c) accompanied by open and transparent communication throughout all stages so that citizens can both understand and participate in decision-making.",,"['Smith, Maxwell J.', 'Bensimon, Cécile M.', 'Perez, Daniel F.', 'Sahni, Sachin S.', 'Upshur, Ross E. G.']",,,,
,PMC,Quiz Corner,,PMC3418778,,,,,,,,,
,PMC,"Crossing Borders: One World, Global Health",http://dx.doi.org/10.1093/cid/cis634,PMC3888076,,,,,,,,,
,PMC,The regulatory T cells in anti-influenza antibody response post influenza vaccination,http://dx.doi.org/10.4161/hv.21117,PMC3579905,,,"The efficacy and effectiveness of influenza vaccines depend primarily on the vaccine recipient and the virus similarity to the endemic virus. Regulatory T cells (Tregs) and cytokines are known to restrict immune responses against viral infections. We conducted this study to explore the role of Tregs, cytokines, and antibody production after influenza vaccination. The whole blood was collected from healthy subjects (n = 36) before and two weeks after influenza vaccine immunization for two or three consecutive years. The cell surface markers, intracellular staining of Foxp3(+) Tregs, and Th1/Th2 cytokines were determined. The antibody titer was detected using the hemagglutination inhibition test. The CD3(+), CD127(+), CD4(+)CD25(+) and CD4(+)Foxp3(+)cells were increased significantly post vaccination. The plasma level of the transforming growth factor (TGF-β), but not interleukin (IL)-2, IL-4, IL-5, IL-10, IFN-γ, TNF-α, was also found to increase significantly after vaccination. We further correlated the cytokine fold-increases with the anti-influenza antibody titer for individual post vaccination. It was found that the IL-10 level after vaccination correlated with the fold-increases of anti-H1N1, anti-H3N2, anti-B/Yamagata, and anti-B/Victoria antibodies. But, a negative relationship occurs between the TGF-β level and fold-increases of anti-H1N1, anti-H3N2, anti-B/Yamagata, and anti-B/Victoria antibodies post vaccination. Treg cells and TGF-β seem to participate in the downregulation of the anti-influenza antibody response post influenza vaccination. Alteration of Treg activity might enhance influenza vaccine antibody responses and efficacy.",,"['Wang, Shih-Min', 'Tsai, Ming-Hsun', 'Lei, Huan-Yao', 'Wang, Jen-Ren', 'Liu, Ching-Chuan']",,,,
,PMC,PAMPs and DAMPs: Signal 0s that Spur Autophagy and Immunity,http://dx.doi.org/10.1111/j.1600-065X.2012.01146.x,PMC3662247,,,"Pathogen-associated molecular pattern molecules (PAMPs) are derived from microorganisms and recognized by pattern recognition receptor (PRR)-bearing cells of the innate immune system as well as many epithelial cells. In contrast, damage-associated molecular pattern molecules (DAMPs) are cell-derived and initiate and perpetuate immunity in response to trauma, ischemia, and tissue damage, either in the absence or presence of pathogenic infection. Most PAMPs and DAMPs serve as so-called ‘Signal 0s’ that bind specific receptors [Toll-like receptors, NOD-like receptors, RIG-I-like receptors, AIM2-like receptors, and the receptor for advanced glycation end products (RAGE)] to promote autophagy. Autophagy, a conserved lysosomal degradation pathway, is a cell survival mechanism invoked in response to environmental and cellular stress. Autophagy is inferred to have been present in the last common eukaryotic ancestor and only to have been lost by some obligatory intracellular parasites. As such, autophagy represents a unifying biology, subserving survival and the earliest host defense strategies, predating apoptosis, within eukaryotes. Here, we review recent advances in our understanding of autophagic molecular mechanisms and functions in emergent immunity.",,"['Tang, Daolin', 'Kang, Rui', 'Coyne, Carolyn B.', 'Zeh, Herbert J.', 'Lotze, Michael T.']",,,,
,PMC,Macrophage Autophagy in Immunity to Cryptococcus neoformans and Candida albicans,http://dx.doi.org/10.1128/IAI.00358-12,PMC3418760,,,"Autophagy is used by eukaryotes in bulk cellular material recycling and in immunity to intracellular pathogens. We evaluated the role of macrophage autophagy in the response to Cryptococcus neoformans and Candida albicans, two important opportunistic fungal pathogens. The autophagosome marker LC3 (microtubule-associated protein 1 light chain 3 alpha) was present in most macrophage vacuoles containing C. albicans. In contrast, LC3 was found in only a few vacuoles containing C. neoformans previously opsonized with antibody but never after complement-mediated phagocytosis. Disruption of host autophagy in vitro by RNA interference against ATG5 (autophagy-related 5) decreased the phagocytosis of C. albicans and the fungistatic activity of J774.16 macrophage-like cells against both fungi, independent of the opsonin used. ATG5-knockout bone marrow-derived macrophages (BMMs) also had decreased fungistatic activity against C. neoformans when activated. In contrast, nonactivated ATG5-knockout BMMs actually restricted C. neoformans growth more efficiently, suggesting that macrophage autophagy plays different roles against C. neoformans, depending on the macrophage type and activation. Interference with autophagy in J774.16 cells also decreased nonlytic exocytosis of C. neoformans, increased interleukin-6 secretion, and decreased gamma interferon-induced protein 10 secretion. Mice with a conditionally knocked out ATG5 gene in myeloid cells showed increased susceptibility to intravenous C. albicans infection. In contrast, these mice manifested no increased susceptibility to C. neoformans, as measured by survival, but had fewer alternatively activated macrophages and less inflammation in the lungs after intratracheal infection than control mice. These results demonstrate the complex roles of macrophage autophagy in restricting intracellular parasitism by fungi and reveal connections with nonlytic exocytosis, humoral immunity, and cytokine signaling.",,"['Nicola, André Moraes', 'Albuquerque, Patrícia', 'Martinez, Luis R.', 'Dal-Rosso, Rafael Antonio', 'Saylor, Carolyn', 'De Jesus, Magdia', 'Nosanchuk, Joshua D.', 'Casadevall, Arturo']",,,,
,PMC,Mycobacterium avium subsp. paratuberculosis Inhibits Gamma Interferon-Induced Signaling in Bovine Monocytes: Insights into the Cellular Mechanisms of Johne's Disease,http://dx.doi.org/10.1128/IAI.00406-12,PMC3418731,,,"Mycobacterium avium subsp. paratuberculosis is the causative agent of Johne's disease in cattle and may have implications for human health. Establishment of chronic infection by M. avium subsp. paratuberculosis depends on its subversion of host immune responses. This includes blocking the ability of infected macrophages to be activated by gamma interferon (IFN-γ) for clearance of this intracellular pathogen. To define the mechanism by which M. avium subsp. paratuberculosis subverts this critical host cell function, patterns of signal transduction to IFN-γ stimulation of uninfected and M. avium subsp. paratuberculosis-infected bovine monocytes were determined through bovine-specific peptide arrays for kinome analysis. Pathway analysis of the kinome data indicated activation of the JAK-STAT pathway, a hallmark of IFN-γ signaling, in uninfected monocytes. In contrast, IFN-γ stimulation of M. avium subsp. paratuberculosis-infected monocytes failed to induce patterns of peptide phosphorylation consistent with JAK-STAT activation. The inability of IFN-γ to induce differential phosphorylation of peptides corresponding to early JAK-STAT intermediates in infected monocytes indicates that M. avium subsp. paratuberculosis blocks responsiveness at, or near, the IFN-γ receptor. Consistent with this hypothesis, increased expression of negative regulators of the IFN-γ receptors SOCS1 and SOCS3 as well as decreased expression of IFN-γ receptor chains 1 and 2 is observed in M. avium subsp. paratuberculosis-infected monocytes. These patterns of expression are functionally consistent with the kinome data and offer a mechanistic explanation for this critical M. avium subsp. paratuberculosis behavior. Understanding this mechanism may contribute to the rational design of more effective vaccines and/or therapeutics for Johne's disease.",,"['Arsenault, Ryan J.', 'Li, Yue', 'Bell, Kelli', 'Doig, Kimberley', 'Potter, Andrew', 'Griebel, Philip J.', 'Kusalik, Anthony', 'Napper, Scott']",,,,
,PMC,Handling of Adolescent Rats Improves Learning and Memory and Decreases Anxiety,,PMC3447442,,,"Some environmental interventions can result in physiologic and behavioral changes in laboratory animals. In this context, the handling of adolescent or adult rodents has been reported to influence exploratory behavior and emotionality. Here we examined the effects of handling on memory and anxiety levels of adolescent rats. Male Sprague–Dawley rats (age, 60 d) were divided into a control group and a handled group, which were handled for 5 min daily, 5 d per week, for 6 wk. During handling bouts, the rat was removed from its cage, placed in the experimenter's lap or on the top of a table, and had its neck and back gently stroked by the experimenter's fingers. During week 6, each rat's anxiety level was evaluated in the elevated plus-maze (EPM) test. Learning and memory were evaluated 48 h later, by measuring escape latency in the elevated plus-maze test. Plasma corticosterone and catecholamine levels were measured also. Norepinephrine levels were lower in the handled rats compared with control animals, with no differences in epinephrine and corticosterone. As compared with the control rats, the handled rats showed increases in the percentage of time spent in the open arms of the test apparatus, percentage of entries into open arms, and number of visits to the end of the open arms and decreases in the latency of the first open arm entry. Escape latency was lower in the handled rats compared with control rats in both the first and second trials. The data obtained suggest that handling decreases anxiety levels and improves learning skills and memory in rats.",,"['Costa, Rafaela', 'Tamascia, Mariana L', 'Nogueira, Marie D', 'Casarini, Dulce E', 'Marcondes, Fernanda K']",,,,
,PMC,"Development and Assay of RNA Transcripts of Enterovirus Species A to D, Rhinovirus Species A to C, and Human Parechovirus: Assessment of Assay Sensitivity and Specificity of Real-Time Screening and Typing Methods",http://dx.doi.org/10.1128/JCM.01172-12,PMC3421820,,,"Nucleic acid amplification methods such as the PCR have had a major impact on the diagnosis of viral infections, often achieving greater sensitivities and shorter turnaround times than conventional assays and an ability to detect viruses refractory to conventional isolation methods. Their effectiveness is, however, significantly influenced by assay target sequence variability due to natural diversity and rapid sequence changes in viruses that prevent effective binding of primers and probes. This was investigated for a diverse range of enteroviruses (EVs; species A to D), human rhinoviruses (HRVs; species A to C), and human parechovirus (HPeV) in a multicenter assay evaluation using a series of full-length prequantified RNA transcripts. RNA concentrations were quantified by absorption (NanoDrop) and fluorescence methods (RiboGreen) prior to dilution in buffer supplemented with RNase inhibitors and carrier RNA. RNA transcripts were extremely stable, showing minimal degradation after prolonged storage at temperatures between ambient and −20°C and after multiple freeze-thaw cycles. Transcript dilutions distributed to six referral laboratories were screened by real-time reverse transcriptase PCR assays using different primers and probes. All of the laboratories reported high assay sensitivities for EV and HPeV transcripts approaching single copies and similar amplification kinetics for all four EV species. HRV detection sensitivities were more variable, often with substantially impaired detection of HRV species C. This could be accounted for in part by the placement of primers and probes to genetically variable target regions. Transcripts developed in this study provide reagents for the ongoing development of effective diagnostics that accommodate increasing knowledge of genetic heterogeneity of diagnostic targets.",,"['McLeish, Nigel J.', 'Witteveldt, Jeroen', 'Clasper, Lucy', 'McIntyre, Chloe', 'McWilliam Leitch, E. Carol', 'Hardie, Alison', 'Bennett, Susan', 'Gunson, Rory', 'Carman, William F.', 'Feeney, Susan A.', 'Coyle, Peter V.', 'Vipond, Barry', 'Muir, Peter', 'Benschop, Kimberley', 'Wolthers, Katja', 'Waris, Matti', 'Osterback, Riikka', 'Johannessen, Ingo', 'Templeton, Kate', 'Harvala, Heli', 'Simmonds, Peter']",,,,
,PMC,Natural and experimental Helicobacter pullorum infection in Brown Norway rats,http://dx.doi.org/10.1099/jmm.0.042374-0,PMC3541769,,,"Helicobacter pullorum is an enterohepatic Helicobacter species (EHS) that was recently reported as a naturally acquired infection in mice. Faecal samples from 18 out of 20 Brown Norway (BN) rats, housed in the same barrier as the H. pullorum-infected mice, were positive for H. pullorum using species-specific PCR. In addition, we determined whether H. pullorum was able to persistently colonize the gastrointestinal tract and/or biliary tree and elicit tissue inflammation as well as a serum IgG response in BN rats. Six (four male, two female) 6-week-old, H. pullorum-negative BN rats were orally dosed with 4×10(8) c.f.u. of H. pullorum every other day for a total of three doses. At 2 weeks post-infection, all rats were H. pullorum-positive by faecal PCR. Five out of the six BN rats remained H. pullorum-positive for the entire 30 week study. PCR analysis of tissue collected at necropsy confirmed that the colon and caecum were the primary sites of H. pullorum colonization. Rats that were persistently colonized by H. pullorum had a sustained H. pullorum-specific IgG response measured by ELISA. Intestinal or hepatic pathology associated with H. pullorum infection was not noted. To our knowledge, this is the first report documenting that rats can be persistently colonized with an EHS that also infects humans.",,"['Cacioppo, Laura D.', 'Turk, Michelle L.', 'Shen, Zeli', 'Ge, Zhongming', 'Parry, Nicola', 'Whary, Mark T.', 'Boutin, Samuel R.', 'Klein, Hilton J.', 'Fox, James G.']",,,,
,PMC,Reply to “Nuclear Export Signal and Immunodominant CD8(+) T Cell Epitope in Influenza A Virus Matrix Protein 1”,http://dx.doi.org/10.1128/JVI.01245-12,PMC3446633,,,,,"['Cao, Shuai', 'Shi, Yi', 'Tan, Shuguang', 'Song, Hao', 'Gao, George F.', 'Liu, Wenjun']",,,,
,PMC,ORF45 of Kaposi's Sarcoma-Associated Herpesvirus Inhibits Phosphorylation of Interferon Regulatory Factor 7 by IKKε and TBK1 as an Alternative Substrate,http://dx.doi.org/10.1128/JVI.05224-11,PMC3446610,,,"Open reading frame 45 (ORF45) of Kaposi's sarcoma-associated herpesvirus (KSHV) is an immediate-early and tegument protein that plays critical roles in antagonizing host antiviral responses. We have previously shown (Zhu et al, Proc. Natl. Acad. Sci. U. S. A., 99:5573–5578, 2002) that ORF45 suppresses activation of interferon regulatory factor 7 (IRF7), a crucial regulator of type I interferon gene expression, by blocking its virus-induced phosphorylation and nuclear accumulation. We report here further characterization of the mechanisms by which ORF45 inhibits IRF7 phosphorylation. In most cell types, IRF7 is phosphorylated and activated by IKKε and TBK1 after viral infection. We found that phosphorylation of IRF7 on Ser477 and Ser479 by IKKε or TBK1 is inhibited by ORF45. The inhibition is specific to IRF7 because phosphorylation of its close relative IRF3 is not affected by ORF45, implying that ORF45 does not inactivate the kinases directly. In fact, we found that ORF45 is phosphorylated efficiently on Ser41 and Ser162 by IKKε and TBK1. We demonstrated that ORF45 competes with the associated IRF7 and inhibits its phosphorylation by IKKε or TBK1 by acting as an alternative substrate.",,"['Liang, Qiming', 'Fu, Bishi', 'Wu, Fayi', 'Li, Xiaojuan', 'Yuan, Yan', 'Zhu, Fanxiu']",,,,
,PMC,Complete Genome Sequence of a Novel Porcine Epidemic Diarrhea Virus in South China,http://dx.doi.org/10.1128/JVI.01589-12,PMC3446595,,,"Since early 2010, outbreaks of porcine epidemic diarrhea (PED) have been observed frequently in immunized swine herds in southern China. The suckling piglets are particularly susceptible to porcine epidemic diarrhea virus (PEDV), with a high mortality rate (90%). Recently, a virulent PEDV strain, GD-A, was isolated from an immunized-swine breeding farm in Guangdong, China. This report describes the complete genome sequence of GD-A, and the data will provide important insights into the variation of PEDV field isolates in southern China.",,"['Fan, Huiying', 'Zhang, Jie', 'Ye, Yu', 'Tong, Tiezhu', 'Xie, Kangshang', 'Liao, Ming']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Replication Is Severely Impaired by MG132 due to Proteasome-Independent Inhibition of M-Calpain,http://dx.doi.org/10.1128/JVI.01001-12,PMC3446591,,,"The ubiquitin-proteasome system (UPS) is involved in the replication of a broad range of viruses. Since replication of the murine hepatitis virus (MHV) is impaired upon proteasomal inhibition, the relevance of the UPS for the replication of the severe acute respiratory syndrome coronavirus (SARS-CoV) was investigated in this study. We demonstrate that the proteasomal inhibitor MG132 strongly inhibits SARS-CoV replication by interfering with early steps of the viral life cycle. Surprisingly, other proteasomal inhibitors (e.g., lactacystin and bortezomib) only marginally affected viral replication, indicating that the effect of MG132 is independent of proteasomal impairment. Induction of autophagy by MG132 treatment was excluded from playing a role, and no changes in SARS-CoV titers were observed during infection of wild-type or autophagy-deficient ATG5(−/−) mouse embryonic fibroblasts overexpressing the human SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2). Since MG132 also inhibits the cysteine protease m-calpain, we addressed the role of calpains in the early SARS-CoV life cycle using calpain inhibitors III (MDL28170) and VI (SJA6017). In fact, m-calpain inhibition with MDL28170 resulted in an even more pronounced inhibition of SARS-CoV replication (>7 orders of magnitude) than did MG132. Additional m-calpain knockdown experiments confirmed the dependence of SARS-CoV replication on the activity of the cysteine protease m-calpain. Taken together, we provide strong experimental evidence that SARS-CoV has unique replication requirements which are independent of functional UPS or autophagy pathways compared to other coronaviruses. Additionally, this work highlights an important role for m-calpain during early steps of the SARS-CoV life cycle.",,"['Schneider, Martha', 'Ackermann, Kerstin', 'Stuart, Melissa', 'Wex, Claudia', 'Protzer, Ulrike', 'Schätzl, Hermann M.', 'Gilch, Sabine']",,,,
,PMC,Distinct Roles for Extracellular Signal-Regulated Kinase 1 (ERK1) and ERK2 in the Structure and Production of a Primate Gammaherpesvirus,http://dx.doi.org/10.1128/JVI.00695-12,PMC3446570,,,"During their progression from intranuclear capsids to mature trilaminar virions, herpesviruses incorporate an extensive array of viral as well as a smaller subset of cellular proteins. Our laboratory previously reported that rhesus monkey rhadinovirus (RRV), a close homolog of the human pathogen Kaposi's sarcoma-associated herpesvirus (KSHV), is comprised of at least 33 different virally encoded proteins. In the current study, we found that RRV infection activated the extracellular signal-regulated kinase (ERK) pathway and nascent virions preferentially incorporated the activated form of ERK2 (pERK2) into the tegument. This was evident even in the face of greatly diminished stores of intracellular ERK2, suggesting a clear bias toward the incorporation of pERK2 into the RRV particle. Similar to earlier findings with KSHV, activation of ERK was essential for the production of lytic viral proteins and virions. Knockdown of intracellular ERK, however, failed to inhibit virus production, likely due to maintenance of residual pools of intracellular pERK2. Paradoxically, selective knockdown of ERK1 enhanced virion production nearly 5-fold and viral titers more than 10-fold. These data are the first to implicate ERK1 as a negative regulator of lytic replication in a herpesvirus and the first to demonstrate the incorporation of an activated signaling molecule within a herpesvirus. Together, the results further our understanding of how herpesviruses interact with host cells during infection and demonstrate how this family of viruses can exploit cellular signal transduction pathways to modulate their own replication.",,"['Woodson, Evonne N.', 'Kedes, Dean H.']",,,,
,PMC,A Common Strategy for Host RNA Degradation by Divergent Viruses,http://dx.doi.org/10.1128/JVI.01230-12,PMC3416159,,,"Infection with gammaherpesviruses, alphaherpesviruses, and betacoronaviruses can result in widespread mRNA degradation, in each case initiated predominantly by a single viral factor. Although not homologous, these factors exhibit significant mechanistic similarities. In cells, each targets translatable RNAs for cleavage and requires host Xrn1 to complete RNA degradation, although the mechanism of targeting and the position of the primary cleavage differ. Thus, multiple host shutoff factors have converged upon a common mRNA degradation pathway.",,"['Gaglia, Marta Maria', 'Covarrubias, Sergio', 'Wong, Wesley', 'Glaunsinger, Britt A.']",,,,
,PMC,Intracytoplasmic Trapping of Influenza Virus by a Lipophilic Derivative of Aglycoristocetin,http://dx.doi.org/10.1128/JVI.07032-11,PMC3416158,,,"We report on a new anti-influenza virus agent, SA-19, a lipophilic glycopeptide derivative consisting of aglycoristocetin coupled to a phenylbenzyl-substituted cyclobutenedione. In Madin-Darby canine kidney cells infected with influenza A/H1N1, A/H3N2, or B virus, SA-19 displayed a 50% antivirally effective concentration of 0.60 μM and a selectivity index (ratio of cytotoxic versus antiviral concentration) of 112. SA-19 was 11-fold more potent than unsubstituted aglycoristocetin and was active in human and nonhuman cell lines. Virus yield at 72 h p.i. was reduced by 3.6 logs at 0.8 μM SA-19. In contrast to amantadine and oseltamivir, SA-19 did not select for resistance upon prolonged virus exposure. SA-19 was shown to inhibit an early postbinding step in virus replication. The compound had no effect on hemagglutinin (HA)-mediated membrane fusion in an HA-polykaryon assay and did not inhibit the low-pH-induced refolding of the HA in a tryptic digestion assay. However, a marked inhibitory effect on the transduction exerted by retroviral pseudoparticles carrying an HA or vesicular stomatitis virus glycoprotein (VSV-G) fusion protein was noted, suggesting that SA-19 targets a cellular factor with a role in influenza virus and VSV entry. Using confocal microscopy with antinucleoprotein staining, SA-19 was proven to completely prevent the influenza virus nuclear entry. This virus arrest was characterized by the formation of cytoplasmic aggregates. SA-19 appeared to disturb the endocytic uptake and trap the influenza virus in vesicles distinct from early, late, or recycling endosomes. The aglycoristocetin derivative SA-19 represents a new class of potent and broad-acting influenza virus inhibitors with potential clinical relevance.",,"['Vanderlinden, Evelien', 'Vanstreels, Els', 'Boons, Eline', 'ter Veer, Wouter', 'Huckriede, Anke', 'Daelemans, Dirk', 'Van Lommel, Alfons', 'Rőth, Erzsébet', 'Sztaricskai, Ferenc', 'Herczegh, Pàl', 'Naesens, Lieve']",,,,
,PMC,Large Ribosomal Protein 4 Increases Efficiency of Viral Recoding Sequences,http://dx.doi.org/10.1128/JVI.01053-12,PMC3416150,,,"Expression of retroviral replication enzymes (Pol) requires a controlled translational recoding event to bypass the stop codon at the end of gag. This recoding event occurs either by direct suppression of termination via the insertion of an amino acid at the stop codon (readthrough) or by alteration of the mRNA reading frame (frameshift). Here we report the effects of a host protein, large ribosomal protein 4 (RPL4), on the efficiency of recoding. Using a dual luciferase reporter assay, we found that transfection of cells with a plasmid encoding RPL4 cDNA increases recoding efficiency in a dose-dependent manner, with a maximal enhancement of nearly twofold. Expression of RPL4 increases recoding of reporters containing retroviral readthrough and frameshift sequences, as well as the Sindbis virus leaky termination signal. RPL4-induced enhancement of recoding is cell line specific and appears to be specific to RPL4 among ribosomal proteins. Cotransfection of RPL4 cDNA with Moloney murine leukemia proviral DNA results in Gag processing defects and a reduction of viral particle formation, presumably caused by the RPL4-dependent alteration of the Gag-to-Gag-Pol ratio required for virion assembly and release.",,"['Green, Lisa', 'Houck-Loomis, Brian', 'Yueh, Andrew', 'Goff, Stephen P.']",,,,
,PMC,Impact on the Endoplasmic Reticulum and Golgi Apparatus of Turnip Mosaic Virus Infection,http://dx.doi.org/10.1128/JVI.01146-12,PMC3416146,,,"The impact of turnip mosaic virus (TuMV) infection on the endomembranes of the host early secretory pathway was investigated using an infectious clone that has been engineered for tagging viral membrane structures with a fluorescent protein fused to the viral protein 6K(2). TuMV infection led to the amalgamation of the endoplasmic reticulum (ER), Golgi apparatus, COPII coatamers, and chloroplasts into a perinuclear globular structure that also contained viral proteins. One consequence of TuMV infection was that protein secretion was blocked at the ER-Golgi interface. Fluorescence recovery after photobleaching (FRAP) experiments indicated that the perinuclear structure cannot be restocked in viral components but was dynamically connected to the bulk of the Golgi apparatus and the ER. Experiments with 6K(2) fused to photoactivable green fluorescent protein (GFP) showed that production of motile peripheral 6K(2) vesicles was functionally linked to the perinuclear structure. Disruption of the early secretory pathway did not prevent the formation of the perinuclear globular structure, enhanced the clustering of peripheral 6K(2) vesicles with COPII coatamers, and led to inhibition of cell-to-cell virus movement. This suggests that a functional secretory pathway is not required for the formation of the TuMV perinuclear globular structure and peripheral vesicles but is needed for successful viral intercellular propagation.",,"['Grangeon, Romain', 'Agbeci, Maxime', 'Chen, Jun', 'Grondin, Gilles', 'Zheng, Huanquan', 'Laliberté, Jean-François']",,,,
,PMC,Mammalian Innate Resistance to Highly Pathogenic Avian Influenza H5N1 Virus Infection Is Mediated through Reduced Proinflammation and Infectious Virus Release,http://dx.doi.org/10.1128/JVI.00244-12,PMC3416141,,,"Respiratory epithelial cells and macrophages are the key innate immune cells that play an important role in the pathogenesis of influenza A virus infection. We found that these two cell types from both human and pig showed comparable susceptibilities to initial infection with a highly pathogenic avian influenza (HPAI) H5N1 virus (A/turkey/Turkey/1/05) and a moderately pathogenic human influenza H1N1 virus (A/USSR/77), but there were contrasting differences in host innate immune responses. Human cells mounted vigorous cytokine (tumor necrosis factor alpha [TNF-α] and interleukin-6 [IL-6]) and chemokine (CXCL9, CXCL10, and CXCL11) responses to H5N1 virus infection. However, pig epithelial cells and macrophages showed weak or no TNF-α and chemokine induction with the same infections. The apparent lack of a strong proinflammatory response, corroborated by the absence of TNF-α induction in H5N1 virus-challenged pigs, coincided with greater cell death and the reduced release of infectious virus from infected pig epithelial cells. Suppressor of cytokine signaling 3 (SOCS3), a protein suppressor of the JAK-STAT pathway, was constitutively highly expressed and transcriptionally upregulated in H5N1 virus-infected pig epithelial cells and macrophages, in contrast to the corresponding human cells. The overexpression of SOCS3 in infected human macrophages dampened TNF-α induction. In summary, we found that the reported low susceptibility of pigs to contemporary Eurasian HPAI H5N1 virus infections coincides at the level of innate immunity of respiratory epithelial cells and macrophages with a reduced output of viable virus and an attenuated proinflammatory response, possibly mediated in part by SOCS3, which could serve as a target in the treatment or prevention of virus-induced hypercytokinemia, as observed for humans.",,"['Nelli, Rahul K.', 'Dunham, Stephen P.', 'Kuchipudi, Suresh V.', 'White, Gavin A.', 'Baquero-Perez, Belinda', 'Chang, Pengxiang', 'Ghaemmaghami, Amir', 'Brookes, Sharon M.', 'Brown, Ian H.', 'Chang, Kin-Chow']",,,,
,PMC,Bats Worldwide Carry Hepatitis E Virus-Related Viruses That Form a Putative Novel Genus within the Family Hepeviridae,http://dx.doi.org/10.1128/JVI.00800-12,PMC3416139,,,"Hepatitis E virus (HEV) is one of the most common causes of acute hepatitis in tropical and temperate climates. Tropical genotypes 1 and 2 are associated with food-borne and waterborne transmission. Zoonotic reservoirs (mainly pigs, wild boar, and deer) are considered for genotypes 3 and 4, which exist in temperate climates. In view of the association of several zoonotic viruses with bats, we analyzed 3,869 bat specimens from 85 different species and from five continents for hepevirus RNA. HEVs were detected in African, Central American, and European bats, forming a novel phylogenetic clade in the family Hepeviridae. Bat hepeviruses were highly diversified and comparable to human HEV in sequence variation. No evidence for the transmission of bat hepeviruses to humans was found in over 90,000 human blood donations and individual patient sera. Full-genome analysis of one representative virus confirmed formal classification within the family Hepeviridae. Sequence- and distance-based taxonomic evaluations suggested that bat hepeviruses constitute a distinct genus within the family Hepeviridae and that at least three other genera comprising human, rodent, and avian hepeviruses can be designated. This may imply that hepeviruses invaded mammalian hosts nonrecently and underwent speciation according to their host restrictions. Human HEV-related viruses in farmed and peridomestic animals might represent secondary acquisitions of human viruses, rather than animal precursors causally involved in the evolution of human HEV.",,"['Drexler, Jan Felix', 'Seelen, Annika', 'Corman, Victor Max', 'Fumie Tateno, Adriana', 'Cottontail, Veronika', 'Melim Zerbinati, Rodrigo', 'Gloza-Rausch, Florian', 'Klose, Stefan M.', 'Adu-Sarkodie, Yaw', 'Oppong, Samuel K.', 'Kalko, Elisabeth K. V.', 'Osterman, Andreas', 'Rasche, Andrea', 'Adam, Alexander', 'Müller, Marcel A.', 'Ulrich, Rainer G.', 'Leroy, Eric M.', 'Lukashev, Alexander N.', 'Drosten, Christian']",,,,
,PMC,Increased Antibody Affinity Confers Broad In Vitro Protection against Escape Mutants of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.00233-12,PMC3416138,,,"Even though the effect of antibody affinity on neutralization potency is well documented, surprisingly, its impact on neutralization breadth and escape has not been systematically determined. Here, random mutagenesis and DNA shuffling of the single-chain variable fragment of the neutralizing antibody 80R followed by bacterial display screening using anchored periplasmic expression (APEx) were used to generate a number of higher-affinity variants of the severe acute respiratory syndrome coronavirus (SARS-CoV)-neutralizing antibody 80R with equilibrium dissociation constants (K(D)) as low as 37 pM, a >270-fold improvement relative to that of the parental 80R single-chain variable fragment (scFv). As expected, antigen affinity was shown to correlate directly with neutralization potency toward the icUrbani strain of SARS-CoV. Additionally, the highest-affinity antibody fragment displayed 10-fold-increased broad neutralization in vitro and completely protected against several SARS-CoV strains containing substitutions associated with antibody escape. Importantly, higher affinity also led to the suppression of viral escape mutants in vitro. Escape from the highest-affinity variant required reduced selective pressure and multiple substitutions in the binding epitope. Collectively, these results support the hypothesis that engineered antibodies with picomolar dissociation constants for a neutralizing epitope can confer escape-resistant protection.",,"['Rani, Mridula', 'Bolles, Meagan', 'Donaldson, Eric F.', 'Van Blarcom, Thomas', 'Baric, Ralph', 'Iverson, Brent', 'Georgiou, George']",,,,
,PMC,Complete Genome Sequence of a Highly Prevalent Isolate of Porcine Epidemic Diarrhea Virus in South China,http://dx.doi.org/10.1128/JVI.01455-12,PMC3416124,,,"A widespread porcine epidemic diarrhea virus (PEDV) occurred in southern China during 2010 to 2012. A virulent field PEDV strain, GD-B, was isolated from a sucking piglet suffering from severe diarrhea in Guangdong, China. We sequenced and analyzed the complete genome of strain GD-B, which will promote a better understanding of the molecular epidemiology and genetic diversity of PEDV field isolates in southern China.",,"['Luo, Yongwen', 'Zhang, Jie', 'Deng, Xianbo', 'Ye, Yu', 'Liao, Ming', 'Fan, Huiying']",,,,
,PMC,DNA Prime-Adenovirus Boost Immunization Induces a Vigorous and Multifunctional T-Cell Response against Hepadnaviral Proteins in the Mouse and Woodchuck Model,http://dx.doi.org/10.1128/JVI.00506-12,PMC3416123,,,"Induction of hepatitis B virus (HBV)-specific cytotoxic T cells by therapeutic immunization may be a strategy to treat chronic hepatitis B. In the HBV animal model, woodchucks, the application of DNA vaccine expressing woodchuck hepatitis virus (WHV) core antigen (WHcAg) in combination with antivirals led to the prolonged control of viral replication. However, it became clear that the use of more potent vaccines is required to overcome WHV persistence. Therefore, we asked whether stronger and more functional T-cell responses could be achieved using the modified vaccines and an optimized prime-boost vaccination regimen. We developed a new DNA plasmid (pCGWHc) and recombinant adenoviruses (AdVs) showing high expression levels of WHcAg. Mice vaccinated with the improved plasmid pCGWHc elicited a stronger WHcAg-specific CD8(+) T-cell response than with the previously used vaccines. Using multicolor flow cytometry and an in vivo cytotoxicity assay, we showed that immunization in a DNA prime-AdV boost regimen resulted in an even more vigorous and functional T-cell response than immunization with the new plasmid alone. Immunization of naïve woodchucks with pCGWHc plasmid or AdVs induced a significant WHcAg-specific degranulation response prior to the challenge, this response had not been previously detected. Consistently, this response led to a rapid control of infection after the challenge. Our results demonstrate that high antigen expression levels and the DNA prime-AdV boost immunization improved the T-cell response in mice and induced significant T-cell responses in woodchucks. Therefore, this new vaccination strategy may be a candidate for a therapeutic vaccine against chronic HBV infection.",,"['Kosinska, Anna D.', 'Johrden, Lena', 'Zhang, Ejuan', 'Fiedler, Melanie', 'Mayer, Anja', 'Wildner, Oliver', 'Lu, Mengji', 'Roggendorf, Michael']",,,,
,PMC,Foot-and-Mouth Disease Virus 3C Protease Cleaves NEMO To Impair Innate Immune Signaling,http://dx.doi.org/10.1128/JVI.00722-12,PMC3416110,,,"Foot-and-mouth disease is a highly contagious viral illness of wild and domestic cloven-hoofed animals. The causative agent, foot-and-mouth disease virus (FMDV), replicates rapidly, efficiently disseminating within the infected host and being passed on to susceptible animals via direct contact or the aerosol route. To survive in the host, FMDV has evolved to block the host interferon (IFN) response. Previously, we and others demonstrated that the leader proteinase (L(pro)) of FMDV is an IFN antagonist. Here, we report that another FMDV-encoded proteinase, 3C(pro), also inhibits IFN-α/β response and the expression of IFN-stimulated genes. Acting in a proteasome- and caspase-independent manner, the 3C(pro) of FMDV proteolytically cleaved nuclear transcription factor kappa B (NF-κB) essential modulator (NEMO), a bridging adaptor protein essential for activating both NF-κB and interferon-regulatory factor signaling pathways. 3C(pro) specifically targeted NEMO at the Gln 383 residue, cleaving off the C-terminal zinc finger domain from the protein. This cleavage impaired the ability of NEMO to activate downstream IFN production and to act as a signaling adaptor of the RIG-I/MDA5 pathway. Mutations specifically disrupting the cysteine protease activity of 3C(pro) abrogated NEMO cleavage and the inhibition of IFN induction. Collectively, our data identify NEMO as a substrate for FMDV 3C(pro) and reveal a novel mechanism evolved by a picornavirus to counteract innate immune signaling.",,"['Wang, Dang', 'Fang, Liurong', 'Li, Kui', 'Zhong, Huijuan', 'Fan, Jinxiu', 'Ouyang, Chao', 'Zhang, Huan', 'Duan, Erzhen', 'Luo, Rui', 'Zhang, Zhongming', 'Liu, Xiangtao', 'Chen, Huanchun', 'Xiao, Shaobo']",,,,
,PMC,Characterization and Complete Genome Sequence of Human Coronavirus NL63 Isolated in China,http://dx.doi.org/10.1128/JVI.01457-12,PMC3416104,,,"Human coronavirus NL63 (HCoV-NL63) was first discovered in Amsterdam in 2004 and was identified as a new human respiratory coronavirus. We here report the first complete genome sequence of HCoV-NL63 strain CBJ 037 isolated in 2008 from a patient with bronchitis in Beijing, China.",,"['Geng, Heyuan', 'Cui, Lijin', 'Xie, Zhengde', 'Lu, Roujian', 'Zhao, Li', 'Tan, Wenjie']",,,,
,PMC,Prospective Multicenter Study of Children With Bronchiolitis Requiring Mechanical Ventilation,http://dx.doi.org/10.1542/peds.2012-0444,PMC3428760,,,"OBJECTIVE: To identify factors associated with continuous positive airway pressure (CPAP) and/or intubation for children with bronchiolitis. METHODS: We performed a 16-center, prospective cohort study of hospitalized children aged <2 years with bronchiolitis. For 3 consecutive years from November 1 until March 31, beginning in 2007, researchers collected clinical data and a nasopharyngeal aspirate from study participants. We oversampled children from the ICU. Samples of nasopharyngeal aspirate were tested by polymerase chain reaction for 18 pathogens. RESULTS: There were 161 children who required CPAP and/or intubation. The median age of the overall cohort was 4 months; 59% were male; 61% white, 24% black, and 36% Hispanic. In the multivariable model predicting CPAP/intubation, the significant factors were: age <2 months (odds ratio [OR] 4.3; 95% confidence interval [CI] 1.7–11.5), maternal smoking during pregnancy (OR 1.4; 95% CI 1.1–1.9), birth weight <5 pounds (OR 1.7; 95% CI 1.0–2.6), breathing difficulty began <1 day before admission (OR 1.6; 95% CI 1.2–2.1), presence of apnea (OR 4.8; 95% CI 2.5–8.5), inadequate oral intake (OR 2.5; 95% CI 1.3–4.3), severe retractions (OR 11.1; 95% CI 2.4–33.0), and room air oxygen saturation <85% (OR 3.3; 95% CI 2.0–4.8). The optimism-corrected c-statistic for the final model was 0.80. CONCLUSIONS: In this multicenter study of children hospitalized with bronchiolitis, we identified several demographic, historical, and clinical factors that predicted the use of CPAP and/or intubation, including children born to mothers who smoked during pregnancy. We also identified a novel subgroup of children who required mechanical respiratory support <1 day after respiratory symptoms began.",,"['Mansbach, Jonathan M.', 'Piedra, Pedro A.', 'Stevenson, Michelle D.', 'Sullivan, Ashley F.', 'Forgey, Tate F.', 'Clark, Sunday', 'Espinola, Janice A.', 'Camargo, Carlos A.']",,,,
,PMC,Changing Realities in Emerging Zoonoses,http://dx.doi.org/10.1111/j.1863-2378.2012.01529.x,PMC4829064,,,,,"['Richt, J. A.', 'Feldmann, H.']",,,,
,PMC,"Interdisciplinary approaches to understanding disease emergence: The past, present, and future drivers of Nipah virus emergence",http://dx.doi.org/10.1073/pnas.1201243109,PMC3586606,,,"Emerging infectious diseases (EIDs) pose a significant threat to human health, economic stability, and biodiversity. Despite this, the mechanisms underlying disease emergence are still not fully understood, and control measures rely heavily on mitigating the impact of EIDs after they have emerged. Here, we highlight the emergence of a zoonotic Henipavirus, Nipah virus, to demonstrate the interdisciplinary and macroecological approaches necessary to understand EID emergence. Previous work suggests that Nipah virus emerged due to the interaction of the wildlife reservoir (Pteropus spp. fruit bats) with intensively managed livestock. The emergence of this and other henipaviruses involves interactions among a suite of anthropogenic environmental changes, socioeconomic factors, and changes in demography that overlay and interact with the distribution of these pathogens in their wildlife reservoirs. Here, we demonstrate how ecological niche modeling may be used to investigate the potential role of a changing climate on the future risk for Henipavirus emergence. We show that the distribution of Henipavirus reservoirs, and therefore henipaviruses, will likely change under climate change scenarios, a fundamental precondition for disease emergence in humans. We assess the variation among climate models to estimate where Henipavirus host distribution is most likely to expand, contract, or remain stable, presenting new risks for human health. We conclude that there is substantial potential to use this modeling framework to explore the distribution of wildlife hosts under a changing climate. These approaches may directly inform current and future management and surveillance strategies aiming to improve pathogen detection and, ultimately, reduce emergence risk.",,"['Daszak, Peter', 'Zambrana-Torrelio, Carlos', 'Bogich, Tiffany L.', 'Fernandez, Miguel', 'Epstein, Jonathan H.', 'Murray, Kris A.', 'Hamilton, Healy']",,,,
,PMC,The X-ray Crystal Structure of Human Aminopeptidase N Reveals a Novel Dimer and the Basis for Peptide Processing,http://dx.doi.org/10.1074/jbc.M112.398842,PMC3481283,,,"Human aminopeptidase N (hAPN/hCD13) is a dimeric membrane protein and a member of the M1 family of zinc metallopeptidases. Within the rennin-angiotensin system, its enzymatic activity is responsible for processing peptide hormones angiotensin III and IV. In addition, hAPN is also involved in cell adhesion, endocytosis, and signal transduction and it is an important target for cancer therapy. Reported here are the high resolution x-ray crystal structures of the dimeric ectodomain of hAPN and its complexes with angiotensin IV and the peptidomimetic inhibitors, amastatin and bestatin. Each monomer of the dimer is found in what has been termed the closed form in other M1 enzymes and each monomer is characterized by an internal cavity surrounding the catalytic site as well as a unique substrate/inhibitor-dependent loop ordering, which in the case of the bestatin complex suggests a new route to inhibitor design. The hAPN structure provides the first example of a dimeric M1 family member and the observed structural features, in conjunction with a model for the open form, provide novel insights into the mechanism of peptide processing and signal transduction.",,"['Wong, Alan H. M.', 'Zhou, Dongxia', 'Rini, James M.']",,,,
,PMC,Computational drug discovery,http://dx.doi.org/10.1038/aps.2012.109,PMC4003107,,,"Computational drug discovery is an effective strategy for accelerating and economizing drug discovery and development process. Because of the dramatic increase in the availability of biological macromolecule and small molecule information, the applicability of computational drug discovery has been extended and broadly applied to nearly every stage in the drug discovery and development workflow, including target identification and validation, lead discovery and optimization and preclinical tests. Over the past decades, computational drug discovery methods such as molecular docking, pharmacophore modeling and mapping, de novo design, molecular similarity calculation and sequence-based virtual screening have been greatly improved. In this review, we present an overview of these important computational methods, platforms and successful applications in this field.",,"['Ou-Yang, Si-sheng', 'Lu, Jun-yan', 'Kong, Xiang-qian', 'Liang, Zhong-jie', 'Luo, Cheng', 'Jiang, Hualiang']",,,,
,PMC,Foldon unfolding mediates the interconversion between M(pro)-C monomer and 3D domain-swapped dimer,http://dx.doi.org/10.1073/pnas.1205241109,PMC3443179,,,"The C-terminal domain (M(pro)-C) of SARS-CoV main protease adopts two different fold topologies, a monomer and a 3D domain-swapped dimer. Here, we report that M(pro)-C can reversibly interconvert between these two topological states under physiological conditions. Although the swapped α(1)-helix is fully buried inside the protein hydrophobic core, the interconversion of M(pro)-C is carried out without the hydrophobic core being exposed to solvent. The 3D domain swapping of M(pro)-C is activated by an order-to-disorder transition of its C-terminal α(5)-helix foldon. Unfolding of this foldon promotes self-association of M(pro)-C monomers and functions to mediate the 3D domain swapping, without which M(pro)-C can no longer form the domain-swapped dimer. Taken together, we propose that there exists a special dimeric intermediate enabling the protein core to unpack and the α(1)-helices to swap in a hydrophobic environment, which minimizes the energy cost of the 3D domain-swapping process.",,"['Kang, Xue', 'Zhong, Nan', 'Zou, Peng', 'Zhang, Shengnan', 'Jin, Changwen', 'Xia, Bin']",,,,
,PMC,Net −1 frameshifting on a noncanonical sequence in a herpes simplex virus drug-resistant mutant is stimulated by nonstop mRNA,http://dx.doi.org/10.1073/pnas.1206582109,PMC3443137,,,"Ribosomal frameshifting entails slippage of the translational machinery during elongation. Frameshifting permits expression of more than one polypeptide from an otherwise monocistronic mRNA, and can restore expression of polypeptides in the face of frameshift mutations. A common mutation conferring acyclovir resistance in patients with herpes simplex virus disease deletes one cytosine from a run of six cytosines (C-chord) in the viral thymidine kinase (tk) gene. However, this mutation does not abolish TK activity, which is important for pathogenicity. To investigate how this mutant retains TK activity, we engineered and analyzed viruses expressing epitope-tagged TK. We found that the mutant's TK activity can be accounted for by low levels of full-length TK polypeptide produced by net −1 frameshifting during translation. The efficiency of frameshifting was relatively high, 3–5%, as the polypeptide from the reading frame generated by the deletion, which lacks stop codons (nonstop), was poorly expressed mainly because of inefficient protein synthesis. Stop codons introduced into this reading frame greatly increased its expression, but greatly decreased the level of full-length TK, indicating that frameshifting is strongly stimulated by a new mechanism, nonstop mRNA, which we hypothesize involves stalling of ribosomes on the polyA tail. Mutational studies indicated that frameshifting occurs on or near the C-chord, a region lacking a canonical slippery sequence. Nonstop stimulation of frameshifting also occurred when the C-chord was replaced with a canonical slippery sequence from HIV. This mechanism thus permits biologically and clinically relevant TK synthesis, and may occur more generally.",,"['Pan, Dongli', 'Coen, Donald M.']",,,,
,PMC,"Monoamine Transporter Structure, Function, Dynamics, and Drug Discovery: A Computational Perspective",http://dx.doi.org/10.1208/s12248-012-9391-0,PMC3475841,,,"With the breakthrough crystallization of the bacterial leucine transporter protein LeuT, the first available X-ray structure for the neurotransmitter/sodium symporter family, development of 3-D computational models is suddenly essential for structure–function studies on the plasmalemmal monoamine transporters (MATs). LeuT-based MAT models have been used to guide elucidation of substrate and inhibitor binding pockets, and molecular dynamics simulations using these models are providing insight into conformations involved in the substrate translocation cycle. With credible MAT models finally in hand, structure-based virtual screening for novel ligands is yielding lead compounds toward the development of new medications for psychostimulant dependence, attention deficit hyperactivity, depression, anxiety, schizophrenia, and other disorders associated with dopamine, norepinephrine, or serotonin dysregulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1208/s12248-012-9391-0) contains supplementary material, which is available to authorized users.",,"['Manepalli, Sankar', 'Surratt, Christopher K.', 'Madura, Jeffry D.', 'Nolan, Tammy L.']",,,,
,PMC,The potential anticancer activity of extracts derived from the roots of Scutellaria baicalensis on human oral squamous cell carcinoma cells,http://dx.doi.org/10.3892/mco.2012.14,PMC3956248,,,"Various herb products derived from plants have potent biological effects including anticancer activity. In the present study, the antitumor activity of a herbal product derived from the Scutellaria baicalensis (S. baicalensis) was examined, using in vitro assays in a human oral squamous cell carcinoma (OSCC) cell line. Results showed that S. baicalensis root extract at the concentration of 100 μg/ml inhibited monolayer- and anchorage-independent growth in human OSCC cell lines, while not affecting the adhering abilities of cells. This suggested that it did not alter the expression of any of the adhesion receptors that mediate cell-extracellular matrix (ECM) interactions. The S. baicalensis root extract demonstrated potent cytostatic and apoptotic effects due to the downregulation of the cyclin-dependent kinase 4 expression and its partner cyclin D1, resulting in G1 arrest and poly (ADP-ribose) polymerase (PARP) cleavage. Additionally, the S. baicalensis root extract was found to have blocked vascular endothelial growth factor (VEGF)-induced migration and tube formation in human endothelial cells. Taken together, these results demonstrate that as a herbal product, the S. baicalensis root extract is a potential inhibitor of tumori- and angiogenesis and may be valuable in the development of pharmaceutical medications for the treatment of oral squamous cell carcinoma.",,"['SATO, DAISUKE', 'KONDO, SEIJI', 'YAZAWA, KAZUNAGA', 'MUKUDAI, YOSHIKI', 'LI, CHUNNAN', 'KAMATANI, TAKAAKI', 'KATSUTA, HIDEYUKI', 'YOSHIHAMA, YASUTO', 'SHIROTA, TATSUO', 'SHINTANI, SATORU']",,,,
,PMC,Flagging and Docking: dual roles for N-glycans in protein quality control and cellular proteostasis,http://dx.doi.org/10.1016/j.tibs.2012.07.005,PMC3459134,,,"Nascent polypeptides entering the endoplasmic reticulum (ER) are covalently modified with pre-assembled oligosaccharides. The terminal glucose and mannose residues are immediately removed after the transfer of the oligosaccharide onto newly synthesized polypeptides. This processing determines whether the polypeptide will be retained in the ER, transported along the secretory pathway, or dislocated across the ER membrane for destruction. Recently, new avenues of research and some issues of controversy have been opened by the discovery that lectin-oligosaccharide interactions stabilize supramolecular complexes between regulators of ER-associated degradation (ERAD). In this Opinion, we propose a unified model that depicts carbohydrates acting both as flags signaling the fitness of a maturing protein, and as docking sites that regulate assembly and stability of the ERAD machinery.",,"['Hebert, Daniel N.', 'Molinari, Maurizio']",,,,
,PMC,Assessing the impact of feline immunodeficiency virus and bovine tuberculosis co-infection in African lions,http://dx.doi.org/10.1098/rspb.2012.1503,PMC3441087,,,"Bovine tuberculosis (BTB), caused by Mycobacterium bovis, is a disease that was introduced relatively recently into the Kruger National Park (KNP) lion population. Feline immunodeficiency virus (FIV(ple)) is thought to have been endemic in lions for a much longer time. In humans, co-infection between Mycobacterium tuberculosis and human immunodeficiency virus increases disease burden. If BTB were to reach high levels of prevalence in lions, and if similar worsening effects would exist between FIV(ple) and BTB as for their human equivalents, this could pose a lion conservation problem. We collected data on lions in KNP from 1993 to 2008 for spatio-temporal analysis of both FIV(ple) and BTB, and to assess whether a similar relationship between the two diseases exists in lions. We found that BTB prevalence in the south was higher than in the north (72 versus 19% over the total study period) and increased over time in the northern part of the KNP (0–41%). No significant spatio-temporal differences were seen for FIV(ple) in the study period, in agreement with the presumed endemic state of the infection. Both infections affected haematology and blood chemistry values, FIV(ple) in a more pronounced way than BTB. The effect of co-infection on these values, however, was always less than additive. Though a large proportion (31%) of the lions was co-infected with FIV(ple) and M. bovis, there was no evidence for a synergistic relation as in their human counterparts. Whether this results from different immunopathogeneses remains to be determined.",,"['Maas, M.', 'Keet, D. F.', 'Rutten, V. P. M. G.', 'Heesterbeek, J. A. P.', 'Nielen, M.']",,,,
,PMC,Focused ultrasound for targeted delivery of siRNA and efficient knockdown of Htt expression,http://dx.doi.org/10.1016/j.jconrel.2012.08.012,PMC4010143,,,"RNA interference is a promising strategy for treatment of Huntington’s disease (HD) as it can specifically decrease the expression of the mutant Huntingtin protein (Htt). However, siRNA does not cross the blood-brain barrier and therefore delivery to the brain is limited to direct CNS delivery. Non-invasive delivery of siRNA through the blood-brain barrier (BBB) would be a significant advantage for translating this therapy to HD patients. Focused ultrasound (FUS), combined with intravascular delivery of microbubble contrast agent, was used to locally and transiently disrupt the BBB in the right striatum of adult rats. 48 hrs following treatment with siRNA, the right (treated) and left (control) striatum was dissected and analyzed for Htt mRNA levels. We demonstrate that FUS can non-invasively deliver siRNA-Htt directly to the striatum leading to a significant reduction of Htt expression in a dose dependent manner. Furthermore, we show that reduction of Htt with siRNA-Htt was greater when the extent of BBB disruption was increased. This study demonstrates that siRNA treatment for knockdown of mutant Htt is feasible without the surgical intervention previously required for direct delivery to the brain.",,"['Burgess, Alison', 'Huang, Yuexi', 'Querbes, William', 'Sah, Dinah W.', 'Hynynen, Kullervo']",,,,
,PMC,New technologies for reporting real-time emergent infections,http://dx.doi.org/10.1017/S0031182012000923,PMC3760201,,,"Novel technologies have prompted a new paradigm in disease surveillance. Advances in computation, communications and materials enable new technologies such as mobile phones and microfluidic chips. In this paper we illustrate examples of new technologies that can augment disease detection. We describe technologies harnessing the internet, mobile phones, point of care diagnostic tools and methods that facilitate detection from passively collected unstructured data. We demonstrate how these can all assist in quicker detection, investigation and response to emerging infectious events. Novel technologies enable collection and dissemination of epidemic intelligence data to both public health practitioners and the general public, enabling finer temporal and spatial resolution of disease monitoring than through traditional public health processes.",,"['CHUNARA, RUMI', 'FREIFELD, CLARK C.', 'BROWNSTEIN, JOHN S.']",,,,
,PMC,Cloning and Sequence Analysis of N Gene of Transmissible Gastroenteritis Virus HYM-09 Isolated from Dog in China,http://dx.doi.org/10.1007/s13337-012-0072-5,PMC3550793,,,"Transmissible gastroenteritis virus (TGEV) is the etiological agent of TGE, and dogs are potential carriers of TGEV. In this study, genomic RNA were extracted from TGEV designated HYM-09 isolated from dog naturally infected with TGEV. The nucleocapsid (N) gene of HYM-09 was amplified by RT-PCR and cloned into pMD18-T vector. The N gene cDNA was sequenced and encompassed an open reading frame of 1,149 nucleotides, encoding a 382-amino acids protein. Sequence analyses of the N genes were performed, including homologous comparison, phylogenetic tree analysis and residue substitution analysis. The results showed that there existed some unique mutations in the HYM-09 isolate N gene, but HYM-09 N gene shared over 96 % homologous identities compared with 12 TGEV reference strains derived from other regions or countries respectively. The phylogenetic tree analysis revealed that the HYM-09 branched into the most strains group. This study shows that the nucleotide sequence analysis can form a base or further study on the mutation trend of non-porcine TGEV.",,"['Man, Chaolai', 'Yu, Xiaolong']",,,,
,PMC,A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence,http://dx.doi.org/10.1016/j.virol.2012.07.020,PMC3484205,,,"We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RVΔG-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RVΔG-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RVΔG-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RVΔG-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.",,"['Papaneri, Amy B.', 'Wirblich, Christoph', 'Cann, Jennifer A.', 'Cooper, Kurt', 'Jahrling, Peter B.', 'Schnell, Matthias J.', 'Blaney, Joseph E.']",,,,
,PMC,Viral infections in patients with hematological malignancies,http://dx.doi.org/10.1038/leusup.2012.15,PMC4851196,,,"Viral infections remain one of the most frequent complications in patients with hematological malignancies, especially in those receiving an allogeneic stem cell transplantation. Viral infections result from reactivation of latent infection rather than from acquisition of new infection. Infections caused by herpes viruses, including cytomegalovirus and Epstein-Barr virus, respiratory viruses and hepatitis B virus are frequently associated with high morbidity and mortality in the immunocompromised host. Major advances have been made primarily by the availability of rapid diagnostic tests and the introduction of potent antiviral compounds into clinical practice.",,"Busca, A",,,,
,PMC,Correction: Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus,http://dx.doi.org/10.1371/annotation/2965cfae-b77d-4014-8b7b-236e01a35492,PMC3436093,,CC BY,,2012 Aug 9,"['Tseng, Chien-Te', 'Sbrana, Elena', 'Iwata-Yoshikawa, Naoko', 'Newman, Patrick C.', 'Garron, Tania', 'Atmar, Robert L.', 'Peters, Clarence J.', 'Couch, Robert B.']",PLoS One,,,
,PMC,Further characterization of the immune response in mice to inactivated and live rabies vaccines expressing Ebola virus glycoprotein,http://dx.doi.org/10.1016/j.vaccine.2012.07.073,PMC3434297,,,"We have previously developed (a) replication-competent, (b) replication-deficient, and (c) chemically inactivated rabies virus (RABV) vaccines expressing ebolavirus (EBOV) glycoprotein (GP) that induce humoral immunity against each virus and confer protection from both lethal RABV and mouse-adapted EBOV challenge in mice. Here, we expand our investigation of the immunogenic properties of these bivalent vaccines in mice. Both live and killed vaccines induced primary EBOV GP-specific T-cells and a robust recall response as measured by interferon-γ ELISPOT assay. In addition to cellular immunity, an effective filovirus vaccine will likely require a multivalent humoral immune response against multiple virus species. As a proof-of-principle experiment, we demonstrated that inactivated RV-GP could be formulated with another inactivated RABV vaccine expressing the nontoxic fragment of botulinum neurotoxin A heavy chain (HC50) without a reduction in immunity to each component. Finally, we demonstrated that humoral immunity to GP could be induced by immunization of mice with inactivated RV-GP in the presence of pre-existing immunity to RABV. The ability of these novel vaccines to induce strong humoral and cellular immunity indicates that they should be further evaluated in additional animal models of infection.",,"['Papaneri, Amy B.', 'Wirblich, Christoph', 'Cooper, Kurt', 'Jahrling, Peter B.', 'Schnell, Matthias J.', 'Blaney, Joseph E.']",,,,
,PMC,Humanization of an anti-CCR4 antibody that kills Cutaneous T-Cell Lymphoma cells and abrogates suppression by T-regulatory cells,http://dx.doi.org/10.1158/1535-7163.MCT-12-0278,PMC3496034,,,"Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of neoplastic disorders characterized by clonally derived and skin-homing malignant T-cells that express high level of chemokine receptor CCR4, which is associated with their skin-homing capacity. CCR4 is also highly expressed on T-regulatory cells (Tregs) that can migrate to several different types of chemotactic ligand CCL17 and CCL22 secreting tumors to facilitate tumor cell evasion from immune surveillance. Thus, its high level expression on CTCL cells and Tregs makes CCR4 a potential ideal target for antibody-based immunotherapy for CTCL and other types of solid tumors. Here we performed humanization and affinity optimization of a murine anti-CCR4 monoclonal antibody (mAb), mAb1567, that recognizes both the N-terminal and extracellular domains of CCR4 with high affinity and inhibits chemotaxis of CCR4(+) CTCL cells. In a mouse CTCL tumor model, mAb1567 exhibited a potent anti-tumor effect and in vitro mechanistic studies showed that both complement-dependent cytotoxicity (CDC) and neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC) likely mediated this effect. MAb1567 also exerts human NK cell-mediated ADCC activity in vitro. Moreover, mAb1567 also effectively inhibits chemotaxis of CD4(+)CD25(high) Tregs via CCL22 and abrogates Treg suppression activity in vitro. An affinity optimized variant of humanized mAb1567, mAb2-3, was selected for further preclinical development based on its higher binding affinity and more potent ADCC and CDC activities. Taken together, this high affinity humanized mAb2-3 with potent anti-tumor effect and a broad range of mechanisms of action may provide a novel immunotherapy for CTCL and other solid tumors.",,"['Chang, De-Kuan', 'Sui, Jianhua', 'Geng, Shusheng', 'Muvaffak, Asli', 'Bai, Mei', 'Fuhlbrigge, Robert C.', 'Lo, Agnes', 'Yammanuru, Anuradha', 'Hubbard, Luke', 'Sheehan, Jared', 'Campbell, James J.', 'Zhu, Quan', 'Kupper, Thomas S.', 'Marasco, Wayne A.']",,,,
,PMC,Extended Protection against Phlebovirus Infection Conferred by Recombinant Adenovirus Expressing Consensus Interferon (DEF201),http://dx.doi.org/10.1128/AAC.00376-12,PMC3421622,,,"Punta Toro virus (PTV; Bunyaviridae, Phlebovirus) is related to Rift Valley fever virus (RVFV), a pathogenic agent which causes severe disease in humans and livestock primarily in the sub-Saharan region of Africa. The recent range expansion of RVFV and the potential for its intentional release into naïve populations pose a significant threat to public health and agriculture. Studies modeling disease in rodents and nonhuman primates have shown that PTV and RVFV are highly sensitive to the antiviral effects of alpha interferon (IFN-α), an important component of the innate antiviral host response. While recombinant IFN-α has high therapeutic value, its utility for the treatment of neglected tropical diseases is hindered by its short in vivo half-life and costly production of longer-lasting pegylated IFNs. Here, we demonstrate extended preexposure protection against lethal PTV challenge following a single intranasal administration of DEF201, which is a replication-deficient human adenovirus type 5 vector engineered to constitutively express consensus IFN-α (cIFN-α) from transduced host cells. DEF201 was also efficacious when administered within 24 h as a postexposure countermeasure. Serum concentrations of cIFN-α could be detected as early as 8 h following treatment and persisted for more than 1 week. The prolonged antiphlebovirus prophylactic effect, low production costs, and ease of administration make DEF201 a promising agent for intervention during natural disease outbreaks and for countering possible bioterrorist acts.",,"['Gowen, Brian B.', 'Ennis, Jane', 'Sefing, Eric J.', 'Wong, Min-Hui', 'Jung, Kie-Hoon', 'Turner, Jeffrey D.']",,,,
,PMC,Effects of Relative Humidity and Spraying Medium on UV Decontamination of Filters Loaded with Viral Aerosols,http://dx.doi.org/10.1128/AEM.00465-12,PMC3406129,,,"Although respirators and filters are designed to prevent the spread of pathogenic aerosols, a stockpile shortage is anticipated during the next flu pandemic. Contact transfer and reaerosolization of collected microbes from used respirators are also a concern. An option to address these potential problems is UV irradiation, which inactivates microbes by dimerizing thymine/uracil in nucleic acids. The objective of this study was to determine the effects of transmission mode and environmental conditions on decontamination efficiency by UV. In this study, filters were contaminated by different transmission pathways (droplet and aerosol) using three spraying media (deionized water [DI], beef extract [BE], and artificial saliva [AS]) under different humidity levels (30% [low relative humidity {LRH}], 60% [MRH], and 90% [HRH]). UV irradiation at constant intensity was applied for two time intervals at each relative humidity condition. The highest inactivation efficiency (IE), around 5.8 logs, was seen for DI aerosols containing MS2 on filters at LRH after applying a UV intensity of 1.0 mW/cm(2) for 30 min. The IE of droplets containing MS2 was lower than that of aerosols containing MS2. Absorption of UV by high water content and shielding of viruses near the center of the aggregate are considered responsible for this trend. Across the different media, IEs in AS and in BE were much lower than in DI for both aerosol and droplet transmission, indicating that solids present in AS and BE exhibited a protective effect. For particles sprayed in a protective medium, RH is not a significant parameter.",,"['Woo, Myung-Heui', 'Grippin, Adam', 'Anwar, Diandra', 'Smith, Tamara', 'Wu, Chang-Yu', 'Wander, Joseph D.']",,,,
,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.12.010812,PMC3417789,,,,,,,,,
,PMC,Dendritic Cells: Arbiters of Immunity and Immunological Tolerance,http://dx.doi.org/10.1101/cshperspect.a007401,PMC3405856,,,"Dendritic cells (DCs) link innate immune sensing of the environment to the initiation of adaptive immune responses. Given their supreme capacity to interact with and present antigen to T cells, DCs have been proposed as key mediators of immunological tolerance in the steady state. However, recent evidence suggests that the role of DCs in central and peripheral T-cell tolerance is neither obligate nor dominant. Instead, DCs appear to regulate multiple aspects of T-cell physiology including tonic antigen receptor signaling, priming of effector T-cell response, and the maintenance of regulatory T cells. These diverse contributions of DCs may reflect the significant heterogeneity and “division of labor” observed between and within distinct DC subsets. The emerging complex role of different DC subsets should form the conceptual basis of DC-based therapeutic approaches toward induction of tolerance or immunization.",,"['Lewis, Kanako L.', 'Reizis, Boris']",,,,
,PMC,HIV: Cell Binding and Entry,http://dx.doi.org/10.1101/cshperspect.a006866,PMC3405824,,,"The first step of the human immunodeficiency virus (HIV) replication cycle—binding and entry into the host cell—plays a major role in determining viral tropism and the ability of HIV to degrade the human immune system. HIV uses a complex series of steps to deliver its genome into the host cell cytoplasm while simultaneously evading the host immune response. To infect cells, the HIV protein envelope (Env) binds to the primary cellular receptor CD4 and then to a cellular coreceptor. This sequential binding triggers fusion of the viral and host cell membranes, initiating infection. Revealing the mechanism of HIV entry has profound implications for viral tropism, transmission, pathogenesis, and therapeutic intervention. Here, we provide an overview into the mechanism of HIV entry, provide historical context to key discoveries, discuss recent advances, and speculate on future directions in the field.",,"['Wilen, Craig B.', 'Tilton, John C.', 'Doms, Robert W.']",,,,
,PMC,Effect of Prophylactic Supplementation with Grape Polyphenolics on Endotoxin-Induced Serum Secretory Phospholipase A(2) Activity in Rats,,PMC3415368,,,"This study investigated whether dietary supplementation of polyphenolics-rich grape extract (GE) could attenuate endotoxin-induced serum secretory phospholipase A(2) (sPLA(2)) activity, a modulator of inflammation. Male Sprague–Dawley rats were fed a control diet or the diet supplemented with polyphenolic-rich GE (100 or 300 mg/kg daily) for 3 wk prior to intraperitoneal injection of 3 or 15 mg/kg LPS. A fluorometric assay was used to measure serum sPLA(2) activity during a 5-d period before and after LPS injection. Body weight, hematocrit, and serum C-reactive protein level were also measured. Administration of LPS induced a rapid increase in sPLA(2) activity, which peaked 1 to 2 d after LPS injection and resolved to near-baseline values on days 4 to 5. Marked declines in body weight and hematocrit, increases in C-reactive protein levels, and effects on health status also occurred. GE supplementation significantly attenuated the LPS-induced increase in sPLA(2) activity and decline in hematocrit, but its effects on the loss of body weight and C-reactive protein levels were not significant. Among the measurements, serum sPLA(2) was the only marker that showed a dose-dependent response to both LPS and GE supplementation. The current findings show that oral consumption of polyphenolic-rich GE suppresses endotoxin-induced sPLA(2) activity.",,"['Tsao, Francis HC', 'Culver, Bryan J', 'Pierre, Joseph F', 'Shanmuganayagam, Dhanansayan', 'Patten, Calvin C', 'Meyer, Keith C']",,,,
,PMC,Infectious Disease Transmission during Organ and Tissue Transplantation,http://dx.doi.org/10.3201/eid1808.120277,PMC3414044,22840823,NO-CC CODE,"Infectious disease transmission through organ and tissue transplantation has been associated with severe complications in recipients. Determination of donor-derived infectious risk associated with organ and tissue transplantation is challenging and limited by availability and performance characteristics of current donor epidemiologic screening (e.g., questionnaire) and laboratory testing tools. Common methods and standards for evaluating potential donors of organs and tissues are needed to facilitate effective data collection for assessing the risk for infectious disease transmission. Research programs can use advanced microbiological technologies to define infectious risks posed by pathogens that are known to be transplant transmissible and provide insights into transmission potential of emerging infectious diseases for which transmission characteristics are unknown. Key research needs are explored. Stakeholder collaboration for surveillance and research infrastructure is required to enhance transplant safety.",2012 Aug,"['Greenwald, Melissa A.', 'Kuehnert, Matthew J.', 'Fishman, Jay A.']",Emerg Infect Dis,,,
,PMC,Response to infections in persons with asthma and atopic disease: epiphenomenon or reflection of host susceptibility,http://dx.doi.org/10.1016/j.jaci.2012.05.056,PMC3410318,,,"Associations between respiratory infections and asthma inception and exacerbations are well established. Infant respiratory syncytial virus and rhinovirus infections are known to be associated with an increased risk of asthma development, and among children with prevalent asthma, 85% of asthma exacerbations are associated with viral infections. However, the exact nature of this relationship remains unclear. Is the increase in severity of infections an epiphenomenon, meaning respiratory infections just appear more severe in individuals with underlying respiratory disease, or instead a reflection of altered host susceptibility among persons with asthma and atopic disease? The main focus of this review is to summarize the available levels of evidence supporting or refuting the notion that persons with asthma or atopic disease have an altered susceptibility to selected pathogens, as well as discussing the biological mechanism(s) that might explain such associations. Finally, we will outline areas in need of further research, as understanding the relationships between infections and asthma has important implications for both asthma prevention and treatment, including potential new pathways that might target host immune response to select pathogens.",,"['James, Kristina M.', 'Peebles, R. Stokes', 'Hartert, Tina V.']",,,,
,PMC,Characterization of a Vibrio fischeri Aminopeptidase and Evidence for Its Influence on an Early Stage of Squid Colonization,http://dx.doi.org/10.1128/JB.00108-12,PMC3416539,,,"Vibrio fischeri cells are the sole colonists of a specialized light organ in the mantle cavity of the sepiolid squid Euprymna scolopes. The process begins when the bacteria aggregate in mucus secretions outside the light organ. The cells eventually leave the aggregate, enter the light organ, and encounter a rich supply of peptides. The need to dissociate from mucus and presumably utilize peptides led us to hypothesize that protease activity is integral to the colonization process. Protease activity associated with whole cells of Vibrio fischeri strain ES114 was identified as the product of a putative cell membrane-associated aminopeptidase (PepN). To characterize this activity, the aminopeptidase was cloned, overexpressed, and purified. Initial steady-state kinetic studies revealed that the aminopeptidase has broad activity, with a preference for basic and hydrophobic side chains and k(cat) and K(m) values that are lower and smaller, respectively, than those of Escherichia coli PepN. A V. fischeri mutant unable to produce PepN is significantly delayed in its ability to colonize squid within the first 12 h, but eventually it establishes a wild-type colonization level. Likewise, in competition with the wild type for colonization, the mutant is outcompeted at 12 h postinoculation but then competes evenly by 24 h. Also, the PepN-deficient strain fails to achieve wild-type levels of cells in aggregates, suggesting an explanation for the initial colonization delay. This study provides a foundation for more studies on PepN expression, localization, and role in the early stages of squid colonization.",,"['Fidopiastis, Pat M.', 'Rader, Bethany A.', 'Gerling, David G.', 'Gutierrez, Nestor A.', 'Watkins, Katherine H.', 'Frey, Michelle West', 'Nyholm, Spencer V.', 'Whistler, Cheryl A.']",,,,
,PMC,The acute respiratory distress syndrome,http://dx.doi.org/10.1172/JCI60331,PMC3408735,,,"The acute respiratory distress syndrome (ARDS) is an important cause of acute respiratory failure that is often associated with multiple organ failure. Several clinical disorders can precipitate ARDS, including pneumonia, sepsis, aspiration of gastric contents, and major trauma. Physiologically, ARDS is characterized by increased permeability pulmonary edema, severe arterial hypoxemia, and impaired carbon dioxide excretion. Based on both experimental and clinical studies, progress has been made in understanding the mechanisms responsible for the pathogenesis and the resolution of lung injury, including the contribution of environmental and genetic factors. Improved survival has been achieved with the use of lung-protective ventilation. Future progress will depend on developing novel therapeutics that can facilitate and enhance lung repair.",,"['Matthay, Michael A.', 'Ware, Lorraine B.', 'Zimmerman, Guy A.']",,,,
,PMC,Relationship between respiratory viral load and lung lesion severity: a study in 24 cases of pandemic H1N1 2009 influenza A pneumonia,http://dx.doi.org/10.3978/j.issn.2072-1439.2012.08.02,PMC3426745,,,"OBJECTIVE: To investigate the relationship between respiratory viral load and lung lesion severity of patients with pandemic H1N1 2009 influenza A pneumonia. STUDY DESIGN: Cross-sectional observation study. METHODS: 24 consecutive H1N1 influenza patients with viral pneumonia (13 males, 11 females, mean age: 17.5 years) during their presentation to hospital were retrospectively analysed. Viral load were first measured on average 5.2 days after the onset of symptoms. The initial CT and viral load measurement was carried on the same day in 13 patients. The rest were carried out with a mean interval time of 1.5 days. All patients had viral load follow-up till turned negative. Thirteen patients had radiological follow-up. RESULTS: There was no significant correlation between the initial lung lesion severity and viral load (P=0.4). Both viral load and lung lesion severity decreased over time, being highest value at initial presentation. The patients had higher initial viral load or higher initial lung lesion severity tended to be slower in resolving. The lung lesion decreased at a slower rate than viral load. CONCLUSIONS: While there was no correlation between the initial viral load and lung lesion severity, these two indices provide valuable information for epidemiological control.",,"['Lu, Pu-Xuan', 'Deng, Ying-Ying', 'Yang, Gui-Lin', 'Liu, Wei-Long', 'Liu, Ying-Xia', 'Huang, Hua', 'Wang, Yi-Xiang J']",,,,
,PMC,Membrane Fusion-Mediated Autophagy Induction Enhances Morbillivirus Cell-to-Cell Spread,http://dx.doi.org/10.1128/JVI.00807-12,PMC3421762,,,"In the context of viral infections, autophagy induction can be beneficial or inhibitory. Within the Paramyxoviridae family, only morbilliviruses have been investigated and are reported to induce autophagy. Here we show that morbilliviruses rapidly induce autophagy and require this induction for efficient cell-to-cell spread. Coexpression of both glycoproteins in cells expressing one of the cellular receptors was required for autophagy induction, and LC3 punctum formation, indicative of autophagy, was mainly observed in syncytia. A similar correlation between syncytium formation and autophagy induction was also observed for other paramyxovirus glycoproteins, suggesting that membrane fusion-mediated autophagy may be common among paramyxoviruses and possibly other enveloped viruses.",,"['Delpeut, Sébastien', 'Rudd, Penny A.', 'Labonté, Patrick', 'von Messling, Veronika']",,,,
,PMC,Suppression of the Interferon and NF-κB Responses by Severe Fever with Thrombocytopenia Syndrome Virus,http://dx.doi.org/10.1128/JVI.00612-12,PMC3421730,,,"Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease characterized by high fever, thrombocytopenia, multiorgan dysfunction, and a high fatality rate between 12 and 30%. It is caused by SFTS virus (SFTSV), a novel Phlebovirus in family Bunyaviridae. Although the viral pathogenesis remains largely unknown, hemopoietic cells appear to be targeted by the virus. In this study we report that human monocytes were susceptible to SFTSV, which replicated efficiently, as shown by an immunofluorescence assay and real-time reverse transcription-PCR. We examined host responses in the infected cells and found that antiviral interferon (IFN) and IFN-inducible proteins were induced upon infection. However, our data also indicated that downregulation of key molecules such as mitochondrial antiviral signaling protein (MAVS) or weakened activation of interferon regulatory factor (IRF) and NF-κB responses may contribute to a restricted innate immunity against the infection. NSs, the nonstructural protein encoded by the S segment, suppressed the beta interferon (IFN-β) and NF-κB promoter activities, although NF-κB activation appears to facilitate SFTSV replication in human monocytes. NSs was found to be associated with TBK1 and may inhibit the activation of downstream IRF and NF-κB signaling through this interaction. Interestingly, we demonstrated that the nucleoprotein (N), also encoded by the S segment, exhibited a suppressive effect on the activation of IFN-β and NF-κB signaling as well. Infected monocytes, mainly intact and free of apoptosis, may likely be implicated in persistent viral infection, spreading the virus to the circulation and causing primary viremia. Our findings provide the first evidence in dissecting the host responses in monocytes and understanding viral pathogenesis in humans infected with a novel deadly Bunyavirus.",,"['Qu, Bingqian', 'Qi, Xian', 'Wu, Xiaodong', 'Liang, Mifang', 'Li, Chuan', 'Cardona, Carol J.', 'Xu, Wayne', 'Tang, Fenyang', 'Li, Zhifeng', 'Wu, Bing', 'Powell, Kira', 'Wegner, Marta', 'Li, Dexin', 'Xing, Zheng']",,,,
,PMC,Complete Genome Sequence of a Novel Type of Human Parechovirus Strain Reveals Natural Recombination Events,http://dx.doi.org/10.1128/JVI.01241-12,PMC3421728,,,"Human parechoviruses (HPeVs) are a species in the Parechovirus genus of the Picornaviridae family. We report a complete genome sequence of a novel HPeV strain, CH-ZJ1, that was found in an infant with gastroenteritis in Zhenjiang City, China. The complete genome consists of 7,298 nucleotides (nt), excluding the 3′ poly(A) tail; the open reading frame is mapped between nucleotide positions 654 and 7211 and encodes a 2,185-amino acid (aa) polyprotein. The phylogenetic tree obtained for the complete genome of this HPeV strain and the other HpeV strains available in GenBank indicated that CH-ZJ1 is intervenient between HpeV type 4 (HpeV4) and HpeV5. Phylogenetic analysis based on the 3D and VP1 genes reveals two incongruent trees. Recombination detection indicated that CH-ZJ1 might be a recombinant which was produced by more than one genomic recombination event that occurred among HPeV1, HPeV4, and HPeV3 strains.",,"['Sun, Guangming', 'Wang, Yong', 'Tao, Gang', 'Shen, Quan', 'Cao, Weiping', 'Chang, Xianlu', 'Zhang, Wen', 'Shao, Chen', 'Yi, Miaoli', 'Shao, Shihe', 'Yang, Yan']",,,,
,PMC,Transport to Late Endosomes Is Required for Efficient Reovirus Infection,http://dx.doi.org/10.1128/JVI.00100-12,PMC3421701,,,"Rab GTPases play an essential role in vesicular transport by coordinating the movement of various types of cargo from one cellular compartment to another. Individual Rab GTPases are distributed to specific organelles and thus serve as markers for discrete types of endocytic vesicles. Mammalian reovirus binds to cell surface glycans and junctional adhesion molecule-A (JAM-A) and enters cells by receptor-mediated endocytosis in a process dependent on β1 integrin. Within organelles of the endocytic compartment, reovirus undergoes stepwise disassembly catalyzed by cathepsin proteases, which allows the disassembly intermediate to penetrate endosomal membranes and release the transcriptionally active viral core into the cytoplasm. The pathway used by reovirus to traverse the endocytic compartment is largely unknown. In this study, we found that reovirus particles traffic through early, late, and recycling endosomes during cell entry. After attachment to the cell surface, reovirus particles and JAM-A codistribute into each of these compartments. Transfection of cells with constitutively active and dominant-negative Rab GTPases that affect early and late endosome biogenesis and maturation influenced reovirus infectivity. In contrast, reovirus infectivity was not altered in cells expressing mutant Rab GTPases that affect recycling endosomes. Thus, reovirus virions localize to early, late, and recycling endosomes during entry into host cells, but only those that traverse early and late endosomes yield a productive infection.",,"['Mainou, Bernardo A.', 'Dermody, Terence S.']",,,,
,PMC,"A Novel Bat Herpesvirus Encodes Homologues of Major Histocompatibility Complex Classes I and II, C-Type Lectin, and a Unique Family of Immune-Related Genes",http://dx.doi.org/10.1128/JVI.00723-12,PMC3421651,,,"Herpesviruses or herpesviral sequences have been identified in various bat species. Here, we report the isolation, cell tropism, and complete genome sequence of a novel betaherpesvirus from the bat Miniopterus schreibersii (MsHV). In primary cell culture, MsHV causes cytopathic effects (CPE) and reaches peak virus production 2 weeks after infection. MsHV was found to infect and replicate less efficiently in a feline kidney cell, CRFK, and failed to replicate in 13 other cell lines tested. Sequencing of the MsHV genome using the 454 system, with a 224-fold coverage, revealed a genome size of 222,870 bp. The genome was extensively analyzed in comparison to those of related viruses. Of the 190 predicted open reading frames (ORFs), 40 were identified as herpesvirus core genes. Among 93 proteins with identifiable homologues in tree shrew herpesvirus (THV), human cytomegalovirus (HCMV), or rat cytomegalovirus (RCMV), most had highest sequence identities with THV counterparts. However, the MsHV genome organization is colinear with that of RCMV rather than that of THV. The following unique features were discovered in the MsHV genome. One predicted protein, B125, is similar to human herpesvirus 6 (HHV-6) U94, a homologue of the parvovirus Rep protein. For the unique ORFs, 7 are predicted to encode major histocompatibility complex (MHC)-related proteins, 2 to encode MHC class I homologues, and 3 to encode MHC class II homologues; 4 encode the homologues of C-type lectin- or natural killer cell lectin-like receptors;, and the products of a unique gene family, the b149 family, of 16 members, have no significant sequence identity with known proteins but exhibit immunoglobulin-like beta-sandwich domains revealed by three-dimensional (3D) structural prediction. To our knowledge, MsHV is the first virus genome known to encode MHC class II homologues.",,"['Zhang, Huajun', 'Todd, Shawn', 'Tachedjian, Mary', 'Barr, Jennifer A.', 'Luo, Minhua', 'Yu, Meng', 'Marsh, Glenn A.', 'Crameri, Gary', 'Wang, Lin-Fa']",,,,
,PMC,The Interactome of the Human Respiratory Syncytial Virus NS1 Protein Highlights Multiple Effects on Host Cell Biology,http://dx.doi.org/10.1128/JVI.00460-12,PMC3421645,,,"Viral proteins can have multiple effects on host cell biology. Human respiratory syncytial virus (HRSV) nonstructural protein 1 (NS1) is a good example of this. During the virus life cycle, NS1 can act as an antagonist of host type I and III interferon production and signaling, inhibit apoptosis, suppress dendritic cell maturation, control protein stability, and regulate transcription of host cell mRNAs, among other functions. It is likely that NS1 performs these different roles through interactions with multiple host cell proteins. To investigate this and identify cellular proteins that could interact with NS1, we used quantitative proteomics in combination with green fluorescent protein (GFP)-trap immunoprecipitation and bioinformatic analysis. This analysis identified 221 proteins that were potentially part of complexes that could interact with NS1, with many of these associated with transcriptional regulation as part of the mediator complex, cell cycle regulation, and other functions previously assigned to NS1. Specific immunoprecipitation using the GFP trap was used to confirm the ability of selected cellular proteins to interact individually with NS1. Infection of A549 cells with recombinant viruses deficient in the expression of NS1 and overexpression analysis both demonstrated that NS1 was necessary and sufficient for the enrichment of cells in the G(1) phase of the cell cycle.",,"['Wu, Weining', 'Tran, Kim C.', 'Teng, Michael N.', 'Heesom, Kate J.', 'Matthews, David A.', 'Barr, John N.', 'Hiscox, Julian A.']",,,,
,PMC,The 26th Annual Symposium of The Protein Society: Abstracts,http://dx.doi.org/10.1002/pro.2113,PMC3449240,,,,,,,,,
,PMC,SARS-CoV Regulates Immune Function-Related Gene Expression in Human Monocytic Cells,http://dx.doi.org/10.1089/vim.2011.0099,PMC3413073,,,"Severe acute respiratory syndrome (SARS) is characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis, and monocytes/macrophages are the key players in the pathogenesis of SARS. In this study, we compared the transcriptional profiles of SARS coronavirus (SARS-CoV)-infected monocytic cells against that infected by coronavirus 229E (CoV-229E). Total RNA was extracted from infected DC-SIGN-transfected monocytes (THP-1-DC-SIGN) at 6 and 24 h after infection, and the gene expression was profiled in oligonucleotide-based microarrays. Analysis of immune-related gene expression profiles showed that at 24 h after SARS-CoV infection: (1) IFN-α/β-inducible and cathepsin/proteasome genes were downregulated; (2) hypoxia/hyperoxia-related genes were upregulated; and (3) TLR/TLR-signaling, cytokine/cytokine receptor-related, chemokine/chemokine receptor-related, lysosome-related, MHC/chaperon-related, and fibrosis-related genes were differentially regulated. These results elucidate that SARS-CoV infection regulates immune-related genes in monocytes/macrophages, which may be important to the pathogenesis of SARS.",,"['Hu, Wanchung', 'Yen, Yu-Ting', 'Singh, Sher', 'Kao, Chuan-Liang', 'Wu-Hsieh, Betty A.']",,,,
,PMC,"Respiratory virus laboratory pandemic planning and surveillance in central Viet Nam, 2008–2010",http://dx.doi.org/10.5365/WPSAR.2012.3.2.012,PMC3731008,,,"INTRODUCTION: Laboratory capacity is needed in central Viet Nam to provide early warning to public health authorities of respiratory outbreaks of importance to human health, for example the outbreak of influenza A(H1N1) pandemic in 2009. Polymerase chain reaction (PCR) procedures established as part of a capacity-building process were used to conduct prospective respiratory surveillance in a region where few previous studies have been undertaken. METHODS: Between October 2008 and September 2010, nose and throat swabs from adults and children (approximately 20 per week) presenting with an acute respiratory illness to the Ninh Hoa General Hospital were collected. Same-day PCR testing and result reporting for 13 respiratory viruses were carried out by locally trained scientists. RESULTS: Of 2144 surveillance samples tested, 1235 (57.6%) were positive for at least one virus. The most common were influenza A strains (17.9%), with pandemic influenza A(H1N1) 2009 and seasonal H3N2 strain accounting for 52% and 43% of these, respectively. Other virus detections included: rhinovirus (12.4%), enterovirus (8.9%), influenza B (8.3%), adenovirus (5.3%), parainfluenza (4.7%), respiratory syncytial virus (RSV) (3.9%), human coronavirus (3.0%) and human metapneumovirus (0.3%). The detection rate was greatest in the 0–5 year age group. Viral co-infections were identified in 148 (6.9%) cases. DISCUSSION: The outbreak in 2009 of the influenza A(H1N1) pandemic strain provided a practical test of the laboratory’s pandemic plan. This study shows that the availability of appropriate equipment and molecular-based testing can contribute to important individual and public health outcomes in geographical locations susceptible to emerging infections.",,"['Tran, Thomas', 'Chien, Bui Trong', 'Papadakis, Georgina', 'Druce, Julian', 'Birch, Chris', 'Chibo, Doris', 'An, Truong Phuoc', 'Trang, Le Thi Kim', 'Trieu, Nguyen Bao', 'Thuy, Doan Thi Thanh', 'Catton, Mike', 'Mai, Trinh Xuan']",,,,
,PMC,"Influence of Tmevpg1, a long intergenic noncoding RNA, on the expression of Ifng by Th1 cells",http://dx.doi.org/10.4049/jimmunol.1200774,PMC3424368,,,"The majority of the genome is noncoding and was believed to be nonfunctional. However, it is now appreciated that transcriptional control of protein coding genes resides within these noncoding regions. Thousands of genes encoding long intergenic noncoding RNAs (lincRNAs) have been recently identified throughout the genome, which positively or negatively regulate transcription of neighboring target genes. Both TMEVPG1 and its mouse orthologue encode lincRNAs and are positioned near the interferon gamma gene (IFNG). Here we show that transcription of both mouse and human TMEVPG1 genes is Th1 selective and dependent upon Stat4 and T-bet, transcription factors that drive the Th1 differentiation program. Ifng expression is partially restored in Stat4(−/−)Tbx21(−/−) cells through co-expression of T-bet and Tmevpg1 and Tmevpg1 expression contributes to but alone is not sufficient to drive Th1-dependent Ifng expression. Our results suggest that TMEVPG1 belongs to the general class of lincRNAs that positively regulate gene transcription.",,"['Collier, Sarah P.', 'Collins, Patrick L.', 'Williams, Christopher L.', 'Boothby, Mark R.', 'Aune, Thomas M.']",,,,
,PMC,CAG expansion induces nucleolar stress in polyglutamine diseases,http://dx.doi.org/10.1073/pnas.1204089109,PMC3421186,,,"The cell nucleus is a major site for polyglutamine (polyQ) toxicity, but the underlying mechanisms involved have yet been fully elucidated. Here, we report that mutant RNAs that carry an expanded CAG repeat (expanded CAG RNAs) induce apoptosis by activating the nucleolar stress pathway in both polyQ patients and transgenic animal disease models. We showed that expanded CAG RNAs interacted directly with nucleolin (NCL), a protein that regulates rRNA transcription. Such RNA–protein interaction deprived NCL of binding to upstream control element (UCE) of the rRNA promoter, which resulted in UCE DNA hypermethylation and subsequently perturbation of rRNA transcription. The down-regulation of rRNA transcription induced nucleolar stress and provoked apoptosis by promoting physical interaction between ribosomal proteins and MDM2. Consequently, p53 protein was found to be stabilized in cells and became concentrated in the mitochondria. Finally, we showed that mitochondrial p53 disrupted the interaction between the antiapoptotic protein, Bcl-xL, and the proapoptotic protein, Bak, which then caused cytochrome c release and caspase activation. Our work provides in vivo evidence that expanded CAG RNAs trigger nucleolar stress and induce apoptosis via p53 and describes a polyQ pathogenic mechanism that involves the nucleolus.",,"['Tsoi, Ho', 'Lau, Terrence Chi-Kong', 'Tsang, Suk-Ying', 'Lau, Kwok-Fai', 'Chan, Ho Yin Edwin']",,,,
,PMC,Encephalitis and CSF increased level of interferon-α in Kikuchi–Fujimoto disease,http://dx.doi.org/10.1136/bcr.01.2012.5579,PMC3433502,,,"Neurological manifestations have been reported in Kikuchi–Fujimoto disease (KFD). Characteristics of brain lesions are not defined. In addition, no biological indexes are known to help clinicians along the diagnosis process. The authors describe encephalitis associated with KFD. Brain MRI, positron emission tomography (PET) scan and a large biological assessment including interferon α (INF-α) level measurement in cerebrospinal fluid (CSF) were performed. A 39-year-old man with chronic headaches developed diplopia, slow ideation and behavioural disturbances. MRI showed brain lesions particularly in the pontine region and internal temporal lobes with enhancement of the perivacular space and the walls of the lateral ventricle. The IFN-α level was increased in the CSF without viral infection. Cervical and mediastinal adenitis were evident as a hypermetabolic focus on a PET scan, and biopsy confirmed the diagnosis of KFD. The encephalitis spontaneously remitted. The authors characterised brain lesions especially related to KFD in association with increased of IFN-α level in the CSF.",,"['Guéguen, Antoine', 'Sené, Thomas', 'Maillart, Elisabeth', 'Gout, Olivier']",,,,
,PMC,A novel coding-region RNA element modulates infectious dengue virus particle production in both mammalian and mosquito cells and regulates viral replication in Aedes aegypti mosquitoes,http://dx.doi.org/10.1016/j.virol.2012.06.028,PMC3683586,,,"Dengue virus (DENV) is an enveloped flavivirus with a positive-sense RNA genome transmitted by Aedes mosquitoes, causing the most important arthropod-borne viral disease affecting humans. Relatively few cis-acting RNA regulatory elements have been described in the DENV coding-region. Here, by introducing silent mutations into a DENV-2 infectious clone, we identify the conserved capsid-coding region 1 (CCR1), an RNA sequence element that regulates viral replication in mammalian cells and to a greater extent in Ae. albopictus mosquito cells. These defects were confirmed in vivo, resulting in decreased replication in Ae. aegypti mosquito bodies and dissemination to the salivary glands. Furthermore, CCR1 does not regulate translation, RNA synthesis or virion retention but likely modulates assembly, as mutations resulted in the release of non-infectious viral particles from both cell types. Understanding the role of CCR1 could help characterize the poorly-defined stage of assembly in the DENV life cycle and uncover novel anti-viral targets.",,"['Groat-Carmona, Anna Maria', 'Orozco, Susana', 'Friebe, Peter', 'Payne, Anne', 'Kramer, Laura', 'Harris, Eva']",,,,
,PMC,A cross-species view on viruses,http://dx.doi.org/10.1016/j.coviro.2012.07.003,PMC3470745,,,"We describe the creative ways that virologists are leveraging experimental cross-species infections to study the interactions between viruses and hosts. While viruses are usually well adapted to their hosts, cross-species approaches involve pairing viruses with species that they don’t naturally infect. These cross-species infections pit viruses against animals, cell lines, or even single genes from foreign species. We highlight examples where cross-species infections have yielded insights into mechanisms of host innate immunity, viral countermeasures, and the evolutionary interplay between viruses and hosts.",,"['Sawyer, Sara L.', 'Elde, Nels C.']",,,,
,PMC,CORONAVIRUS E PROTEIN FORMS ION CHANNELS WITH FUNCTIONALLY AND STRUCTURALLY-INVOLVED MEMBRANE LIPIDS,http://dx.doi.org/10.1016/j.virol.2012.07.005,PMC3438407,,,"Coronavirus (CoV) envelope (E) protein ion channel activity was determined in channels formed in planar lipid bilayers by peptides representing either the transmembrane domain of severe acute respiratory syndrome CoV (SARS-CoV) E protein, or the full-length E protein. Both of them formed a voltage independent ion conductive pore with symmetric ion transport properties. Mutations N15A and V25F located in the transmembrane domain, prevented the ion conductivity. E protein derived channels showed no cation preference in non-charged lipid membranes, whereas they behaved as pores with mild cation selectivity in negatively-charged lipid membranes. The ion conductance was also controlled by the lipid composition of the membrane. Lipid charge also regulated the selectivity of a HCoV-229E E protein derived peptide. These results suggested that the lipids are functionally involved in E protein ion channel activity, forming a protein-lipid pore, a novel concept for CoV E protein ion channel entity.",,"['Verdiá-Báguena, Carmina', 'Nieto-Torres, Jose L.', 'Alcaraz, Antonio', 'DeDiego, Marta L.', 'Torres, Jaume', 'Aguilella, Vicente M.', 'Enjuanes, Luis']",,,,
,PMC,Quantitative Salivary Proteomic Differences in Oral Chronic Graft-versus-Host Disease,http://dx.doi.org/10.1007/s10875-012-9738-4,PMC3805145,,,"PURPOSE: Chronic graft-versus-host disease (cGVHD) is a severe immunological complication that occurs after allogeneic hematopoietic stem cell transplantation (HSCT). Although oral cGVHD occurs in >25 % of cGVHD patients and leads to decreased quality of life, its etiology is poorly understood. The present retrospective cross-sectional analysis of oral cGVHD patients sought to (1) test the feasibility of liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify protein biomarkers of oral cGVHD and (2) to gain a clearer understanding of salivary proteins impacted by oral cGVHD. METHODS: Using unstimulated whole saliva, we compared pooled saliva from five patients with a diagnosis of moderate or severe oral cGVHD, with a gender-and age- matched pool of five cGVHD patients with no oral mucosal findings. LC-MS/MS was used to identify salivary proteins, followed by Ingenuity Pathway Analysis (IPA). Selected mass spectrometric findings, including lactotransferrin, lactoperoxidase, and albumin, were confirmed by targeted label-free quantification. RESULTS: LC-MS/MS led to confident identification of 180 proteins. Of these proteins, 102 changed in abundance at least 2 fold, including 12 proteins identified only in the No oral cGVHD group. Downregulation of ~0.4 fold was confirmed for both lactotransferrin and lactoperoxidase in Oral cGVHD saliva using targeted label-free quantification. IPA analysis implicated pathways involved in cellular metabolism and immunoregulation. CONCLUSIONS: Reduction of salivary lactoperoxidase, lactotransferrin, and several cysteine proteinase inhibitor family proteins suggests impaired oral antimicrobial host immunity in cGVHD patients. This shotgun proteomic analysis of oral cGVHD saliva using targeted label-free quantification of select proteins supports the use of mass spectrometry for future validation in a large patient population as noninvasive tests for screening, early detection, and monitoring of cGVHD.",,"['Bassim, Carol W', 'Ambatipudi, Kiran S.', 'Mays, Jacqueline W.', 'Edwards, Dean A.', 'Swatkoski, Stephan', 'Fassil, Helen', 'Baird, Kristin', 'Gucek, Marjan', 'Melvin, James E.', 'Pavletic, Steven Z.']",,,,
,PMC,Viral acute lower respiratory infections impair CD8(+) T cells through PD-1,http://dx.doi.org/10.1172/JCI62860,PMC3408742,,,"Viruses are leading causes of severe acute lower respiratory infections (LRIs). These infections evoke incomplete immunity, as individuals can be repeatedly reinfected throughout life. We report that acute viral LRI causes rapid pulmonary CD8(+) cytotoxic T lymphocyte (T(CD8)) functional impairment via programmed death–1/programmed death ligand–1 (PD-1/PD-L1) signaling, a pathway previously associated with prolonged antigenic stimulation during chronic infections and cancer. PD-1–mediated T(CD8) impairment occurred acutely in mice following infection with human metapneumovirus or influenza virus. Viral antigen was sufficient for PD-1 upregulation, but induction of PD-L1 was required for impairment. During secondary viral infection or epitope-only challenge, memory T(CD8) rapidly reexpressed PD-1 and exhibited severe functional impairment. Inhibition of PD-1 signaling using monoclonal antibody blockade prevented T(CD8) impairment, reduced viral titers during primary infection, and enhanced protection of immunized mice against challenge infection. Additionally, PD-1 and PD-L1 were upregulated in the lungs of patients with 2009 H1N1 influenza virus, respiratory syncytial virus, or parainfluenza virus infection. These results indicate that PD-1 mediates T(CD8) functional impairment during acute viral infection and may contribute to recurrent viral LRIs. Therefore, the PD-1/PD-L1 pathway may represent a therapeutic target in the treatment of respiratory viruses.",,"['Erickson, John J.', 'Gilchuk, Pavlo', 'Hastings, Andrew K.', 'Tollefson, Sharon J.', 'Johnson, Monika', 'Downing, Melissa B.', 'Boyd, Kelli L.', 'Johnson, Joyce E.', 'Kim, Annette S.', 'Joyce, Sebastian', 'Williams, John V.']",,,,
,PMC,Rapidly Generated Multivirus-specific Cytotoxic T Lymphocytes for the Prophylaxis and Treatment of Viral Infections,http://dx.doi.org/10.1038/mt.2012.130,PMC3412490,,,"Severe and fatal viral infections remain common after hematopoietic stem cell transplantation. Adoptive transfer of cytotoxic T lymphocytes (CTLs) specific for Epstein–Barr virus (EBV), cytomegalovirus (CMV), and adenoviral antigens can treat infections that are impervious to conventional therapies, but broader implementation and extension to additional viruses is limited by competition between virus-derived antigens and time-consuming and laborious manufacturing procedures. We now describe a system that rapidly generates a single preparation of polyclonal (CD4(+) and CD8(+)) CTLs that is consistently specific for 15 immunodominant and subdominant antigens derived from 7 viruses (EBV, CMV, Adenovirus (Adv), BK, human herpes virus (HHV)-6, respiratory syncytial virus (RSV), and Influenza) that commonly cause post-transplant morbidity and mortality. CTLs can be rapidly produced (10 days) by a single stimulation of donor peripheral blood mononuclear cells (PBMCs) with a peptide mixture spanning the target antigens in the presence of the potent prosurvival cytokines interleukin-4 (IL4) and IL7. This approach reduces the impact of antigenic competition with a consequent increase in the antigenic repertoire and frequency of virus-specific T cells. Our approach can be readily introduced into clinical practice and should be a cost-effective alternative to common antiviral prophylactic agents for allogeneic hematopoietic stem cell transplant (HSCT) recipients.",,"['Gerdemann, Ulrike', 'Keirnan, Jacqueline M', 'Katari, Usha L', 'Yanagisawa, Ryu', 'Christin, Anne S', 'Huye, Leslie E', 'Perna, Serena K', 'Ennamuri, Sravya', 'Gottschalk, Stephen', 'Brenner, Malcolm K', 'Heslop, Helen E', 'Rooney, Cliona M', 'Leen, Ann M']",,,,
,PMC,Synthetic constructs in/for the environment: Managing the interplay between natural and engineered Biology,http://dx.doi.org/10.1016/j.febslet.2012.02.022,PMC3396840,22710182,CC BY-NC-ND,"The plausible release of deeply engineered or even entirely synthetic/artificial microorganisms raises the issue of their intentional (e.g. bioremediation) or accidental interaction with the Environment. Containment systems designed in the 1980s–1990s for limiting the spread of genetically engineered bacteria and their recombinant traits are still applicable to contemporary Synthetic Biology constructs. Yet, the ease of DNA synthesis and the uncertainty on how non-natural properties and strains could interplay with the existing biological word poses yet again the challenge of designing safe and efficacious firewalls to curtail possible interactions. Such barriers may include xeno-nucleic acids (XNAs) instead of DNA as information-bearing molecules, rewriting the genetic code to make it non-understandable by the existing gene expression machineries, and/or making growth dependent on xenobiotic chemicals.",2012 Jul 16,"['Schmidt, Markus', 'de Lorenzo, Víctor']",FEBS Lett,,,
,PMC,Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia,http://dx.doi.org/10.1016/j.nbd.2012.07.005,PMC3465075,,,"Immune system factors including complement pathway activation are increasingly linked to the etiology and pathophysiology of schizophrenia. Complement protein, C1q, binds to and helps to clear immune complexes composed of immunoglobulins coupled to antigens. The antigenic stimuli for C1q activation in schizophrenia are not known. Food sensitivities characterized by elevated IgG antibodies to bovine milk caseins and wheat glutens have been reported in individuals with schizophrenia. Here, we examined the extent to which these food products might comprise the antigen component of complement C1q immune complexes in individuals with recent onset schizophrenia (n=38), non-recent onset schizophrenia (n=61) and non-psychiatric controls (n=63). C1q seropositivity was significantly associated with both schizophrenia groups (recent onset, odds ratio (OR)=8.02, p≤0.008; non-recent onset, OR=3.15, p≤0.03) compared to controls (logistic regression models corrected for age, sex, race and smoking status). Casein- and/or gluten-IgG binding to C1q was significantly elevated in the non-recent onset group compared to controls (OR=4.36, p≤0.01). Significant amounts of C1q-casein/gluten-related immune complexes and C1q correlations with a marker for gastrointestinal inflammation in non-recent onset schizophrenia suggests a heightened rate of food antigens in the systemic circulation, perhaps via a disease-associated altered intestinal permeability. In individuals who are in the early stages of disease onset, C1q activation may reflect the formation of immune complexes with non-casein- or non-gluten-related antigens, the presence of C1q autoantibodies, and/or a dissociated state of immune complex components. In conclusion, complement activation may be a useful biomarker to diagnose schizophrenia early during the course of the disease. Future prospective studies should evaluate the impacts of casein- and gluten-free diets on C1q activation in schizophrenia.",,"['Severance, Emily G.', 'Gressitt, Kristin', 'Halling, Meredith', 'Stallings, Cassie R.', 'Origoni, Andrea E.', 'Vaughan, Crystal', 'Khushalani, Sunil', 'Alaedini, Armin', 'Dupont, Didier', 'Dickerson, Faith B.', 'Yolken, Robert H.']",,,,
,PMC,RNA Binding by the NS3 Protease of the Hepatitis C Virus,http://dx.doi.org/10.1016/j.virusres.2012.07.007,PMC3467334,,,"The hepatitis C virus (HCV) nonstructural protein 3 (NS3) is essential for the processing of the HCV polyprotein, the replication of HCV RNA, and to short circuit innate immunity signaling. NS3 contains an N-terminal domain with protease activity and a C-terminal domain with helicase activity. The two domains communicate with each other along with other HCV and cellular proteins. Herein we show that RNAs can bind directly to the active site cleft of the NS3 protease domain (NS3P) and inhibit proteolysis of peptide substrates. RNAs that are less apt to form intramolecular structures have a stronger inhibitory activity than RNAs with more stable base paired regions. Two mutations in the protease domain that resulted in decreased affinity to ssRNA were also defective in RNA-induced ATPase activity from the helicase domain of NS3. The coordinated effects on inhibition of protease activity and stimulation of ATPase activity raise the possibility that RNA serves as a regulatory switch for the two processes.",,"['Vaughan, Robert', 'Li, Yi', 'Fan, Baochang', 'Ranjith-Kumar, C. T.', 'Kao, C. Cheng']",,,,
,PMC,Autophagy in the regulation of pathogen replication and adaptive immunity,http://dx.doi.org/10.1016/j.it.2012.06.003,PMC3461100,,,"Autophagy is an evolutionary conserved homeostatic process by which cells deliver cytoplasmic material for degradation into lysosomes. Autophagy may have evolved as a nutrient-providing homeostatic pathway induced upon starvation, but with the acquisition of cargo-receptors autophagy has become an important cellular defence mechanism as well as a generator of antigenic peptides for MHC presentation. We propose that autophagy efficiently protects against microbes encountering the cytosolic environment accidentally, for example upon phagosomal damage, while pathogens routinely accessing the host cytosol have evolved to avoid or even benefit from autophagy.",,"['Randow, Felix', 'Münz, Christian']",,,,
,PMC,Recent advances in small bowel diseases: Part I,http://dx.doi.org/10.3748/wjg.v18.i26.3336,PMC3396187,,,"As is the case in all parts of gastroenterology and hepatology, there have been many advances in our knowledge and understanding of small intestinal diseases. Over 1000 publications were reviewed for 2008 and 2009, and the important advances in basic science as well as clinical applications were considered. In Part I of this Editorial Review, seven topics are considered: intestinal development; proliferation and repair; intestinal permeability; microbiotica, infectious diarrhea and probiotics; diarrhea; salt and water absorption; necrotizing enterocolitis; and immunology/allergy. These topics were chosen because of their importance to the practicing physician.",,"['Thomson, Alan BR', 'Chopra, Angeli', 'Clandinin, Michael Tom', 'Freeman, Hugh']",,,,
,PMC,Mucroporin-M1 Inhibits Hepatitis B Virus Replication by Activating the Mitogen-activated Protein Kinase (MAPK) Pathway and Down-regulating HNF4α in Vitro and in Vivo,http://dx.doi.org/10.1074/jbc.M112.370312,PMC3436272,,,"Hepatitis B virus (HBV) is a noncytopathic human hepadnavirus that causes acute, chronic hepatitis and hepatocellular carcinoma (HCC). As the clinical utility of current therapies is limited, new anti-HBV agents and sources for such agents are still highly sought after. Here, we report that Mucroporin-M1, a scorpion venom-derived peptide, reduces the amount of extracellular HBsAg, HBeAg, and HBV DNA productions of HepG2.2.15 cells in a dose-dependent manner and inhibits HBV capsid DNA, HBV intracellular RNA replication intermediates and the HBV Core protein in the cytoplasm of HepG2.2.15 cells. Using a mouse model of HBV infection, we found that HBV replication was significantly inhibited by intravenous injection of the Mucroporin-M1 peptide. This inhibitory activity was due to a reduction in HBV promoter activity caused by a decrease in the binding of HNF4α to the precore/core promoter region. Furthermore, we confirmed that Mucroporin-M1 could selectively activate mitogen-activated protein kinases (MAPKs) and lead to the down-regulation of HNF4α expression, which explains the decreased binding of HNF4α to the HBV promoter. Moreover, when the protein phosphorylation activity of the MAPK pathway was inhibited, both HNF4α expression and HBV replication recovered. Finally, we proved that treatment with the Mucroporin-M1 peptide increased phosphorylation of the MAPK proteins in HBV-harboring mice. These results implicate Mucroporin-M1 peptide can activate the MAPK pathway and then reduce the expression of HNF4α, resulting in the inhibition of HBV replication in vitro and in vivo. Our work also opens new doors to discovering novel anti-HBV agents or sources.",,"['Zhao, Zhenhuan', 'Hong, Wei', 'Zeng, Zhengyang', 'Wu, Yingliang', 'Hu, Kanghong', 'Tian, Xiaohui', 'Li, Wenxin', 'Cao, Zhijian']",,,,
,PMC,S1 gene sequence analysis of new variant isolates of avian infectious bronchitis virus in Tunisia,http://dx.doi.org/10.2147/VMRR.S32498,PMC6065601,,,"PURPOSE: Tissue samples were collected from suspected broiler flocks showing respiratory signs to identify infectious bronchitis virus (IBV), characterize emerging field strains, and study their relationships with the Massachusetts H120 strain, the only IB vaccine used in Tunisia. SAMPLES AND METHODS: Several IBV isolates were identified from field samples collected from flocks located in different regions in the northeast of Tunisia. The IBV isolates were characterized and compared to commonly used vaccine strains (including 793B, D274, and H120 types), other reference IBV strains from Europe, and the recently characterized Tunisian field variants TN20/00, TN200/01, and TN335/01. Reverse transcription–polymerase chain reaction and nucleotide sequencing analyses of the hypervariable regions of the S1 gene were carried out. RESULTS: Four new IBV variants were isolated during the period 2007–10 and were designated TN295/07, TN296/07, TN556/07, and TN557/07. The amino acid sequence data showed 100% similarity between TN295/07 and TN296/07, suggesting that these two isolates are identical and belong to the same genotype. Similar results were demonstrated for TN556/07 and TN557/07. Sequence identity values indicated that TN296/07 and TN556/07 share 55% amino acid homologies between each other, but are very different from the reference IBV serotypes, in particular the H120 strain. It was also shown that they have 50%–77% similarities with the Tunisian virus isolated between 2000 and 2001. Phylogenetic clustering allowed classification of these Tunisian isolates as new genotypes that are closer to TN200/01, TN335/01 Tunisian field variants, and Italy02 variant than MassH120 vaccine strain. CONCLUSION: S1 sequence analyses confirmed the cocirculation of H120 vaccine strain with novel IBV variants isolated from Tunisian field.",,"['Bourogâa, Hager', 'Hellal, Imen', 'Hassen, Jihene', 'Fathallah, Imen', 'Ghram, Abdeljelil']",,,,
,PMC,Professionalism: What is it?,http://dx.doi.org/10.1503/cmaj.109-4211,PMC3394816,,,,,"Collier, Roger",,,,
,PMC,Genome-wide gene–environment interaction analysis for asbestos exposure in lung cancer susceptibility,http://dx.doi.org/10.1093/carcin/bgs188,PMC3499061,,,"Asbestos exposure is a known risk factor for lung cancer. Although recent genome-wide association studies (GWASs) have identified some novel loci for lung cancer risk, few addressed genome-wide gene–environment interactions. To determine gene–asbestos interactions in lung cancer risk, we conducted genome-wide gene–environment interaction analyses at levels of single nucleotide polymorphisms (SNPs), genes and pathways, using our published Texas lung cancer GWAS dataset. This dataset included 317 498 SNPs from 1154 lung cancer cases and 1137 cancer-free controls. The initial SNP-level P-values for interactions between genetic variants and self-reported asbestos exposure were estimated by unconditional logistic regression models with adjustment for age, sex, smoking status and pack-years. The P-value for the most significant SNP rs13383928 was 2.17×10(–6), which did not reach the genome-wide statistical significance. Using a versatile gene-based test approach, we found that the top significant gene was C7orf54, located on 7q32.1 (P = 8.90×10(–5)). Interestingly, most of the other significant genes were located on 11q13. When we used an improved gene-set-enrichment analysis approach, we found that the Fas signaling pathway and the antigen processing and presentation pathway were most significant (nominal P < 0.001; false discovery rate < 0.05) among 250 pathways containing 17 572 genes. We believe that our analysis is a pilot study that first describes the gene–asbestos interaction in lung cancer risk at levels of SNPs, genes and pathways. Our findings suggest that immune function regulation-related pathways may be mechanistically involved in asbestos-associated lung cancer risk. Abbreviations: CI: confidence interval E: environment FDR: false discovery rate G: gene GSEA: gene-set-enrichment analysis GWAS: genome-wide association studies i-GSEA: improved gene-set-enrichment analysis approach OR: odds ratio SNP: single nucleotide polymorphism",,"['Wei, Sheng', 'Wang, Li-E', 'McHugh, Michelle K.', 'Han, Younghun', 'Xiong, Momiao', 'Amos, Christopher I.', 'Spitz, Margaret R.', 'Wei, Qingyi Wei']",,,,
,PMC,Chronic psychosocial stress: does it modulate immunity to the influenza vaccine in Hong Kong Chinese elderly caregivers?,http://dx.doi.org/10.1007/s11357-012-9449-z,PMC3705094,,,"Previous studies evaluated the effects of psychosocial stress on influenza vaccine responses. However, there were methodological limitations. This study aims to determine whether chronic stress is associated with poorer influenza-specific immune responses to influenza vaccines in Hong Kong Chinese elderly people. This is a prospective study with a 12-week follow-up. Subjects were recruited from government general out-patient clinics, non-government organizations, and public housing estates in Hong Kong. Participants include 55 caregivers of spouses with chronic conditions that impaired their activities of daily living and 61 age- and sex-matched non-caregivers. A single-dose trivalent influenza vaccine was given to all subjects by intramuscular ingestion. Blood samples were collected before vaccination, at 6 weeks, and at 12 weeks after vaccination. Influenza vaccine strain-specific antibody titers were measured by the hemagglutination inhibition method. Lymphocyte subsets were analyzed for ratios and absolute counts, and cytokine concentration were measured by flow cytometry. Validated scales were used to assess psychological (depressive symptoms, perceived stress, and caregiver strain), social (multidimensional social support scale), and lifestyle factors (physical exercise, cigarette smoking, and alcohol consumption) at baseline prior to vaccination. Demographic and socioeconomic variables were also collected. Albumin levels were measured as an indicator for nutritional status in subjects. Caregivers had statistically significant (p < 0.05) lower cell-mediated immune responses to influenza vaccination at 12 weeks when compared with those of the controls. No differences in humoral immune response to vaccination were observed between caregivers and controls. Hong Kong Chinese elderly who experience chronic stress have a significantly lower cell-mediated immune response to influenza vaccination when compared with non-caregivers.",,"['Wong, Samuel Yeung Shan', 'Wong, Chun Kwok', 'Chan, Frank Wan Kin', 'Chan, Paul K. S.', 'Ngai, Karry', 'Mercer, Stewart', 'Woo, Jean']",,,,
,PMC,Extended JAK Activation and Delayed STAT1 Dephosphorylation Contribute to the Distinct Signaling Profile of CNS Neurons Exposed to Interferon-Gamma,http://dx.doi.org/10.1016/j.jneuroim.2012.06.006,PMC3678282,,,"Although interferon-gamma (IFN-γ) plays a critical role in the noncytolytic elimination of many neurotropic viral infections, the signaling response to this cytokine has not been extensively characterized in primary CNS neurons. We previously demonstrated that the IFN-γ response at the signaling and gene expression levels is temporally extended in primary mouse hippocampal neurons, as compared to the transient response of primary mouse embryonic fibroblasts (MEF). We hypothesize that the protracted kinetics of STAT1 phosphorylation in IFN-γ-treated neurons are due to extended receptor activation and/or delayed STAT1 dephosphorylation in the nucleus. Here, we show that in response to IFN-γ, the Janus kinases (JAK1/JAK2) associated with the neuronal IFN-γ receptor complex remain active for an extended period as compared to MEF. Experimental inactivation of JAK1/JAK2 in neurons after IFN-γ treatment did not reverse the extended STAT1 phosphorylation phenotype. These results suggest that the extended kinetics of neuronal IFN-γ signaling are a product of distinct negative feedback mechanisms operating at both the receptor and within the nucleus.",,"['Podolsky, Michael A.', 'Solomos, Andreas C.', 'Durso, Lisa C.', 'Evans, Stephanie M.', 'Rall, Glenn F.', 'Rose, R. Wesley']",,,,
,PMC,Evolutionary dynamics of genome segmentation in multipartite viruses,http://dx.doi.org/10.1098/rspb.2012.1086,PMC3415918,,,"Multipartite viruses are formed by a variable number of genomic fragments packed in independent viral capsids. This fact poses stringent conditions on their transmission mode, demanding, in particular, a high multiplicity of infection (MOI) for successful propagation. The actual advantages of the multipartite viral strategy are as yet unclear. The origin of multipartite viruses represents an evolutionary puzzle. While classical theories suggested that a faster replication rate or higher replication fidelity would favour shorter segments, recent experimental results seem to point to an increased stability of virions with incomplete genomes as a factor able to compensate for the disadvantage of mandatory complementation. Using as main parameters differential stability as a function of genome length and MOI, we calculate the conditions under which a set of complementary segments of a viral genome would outcompete the non-segmented variant. Further, we examine the likeliness that multipartite viral forms could be the evolutionary outcome of the competition among the defective genomes of different lengths that spontaneously arise under replication of a complete, wild-type genome. We conclude that only multipartite viruses with a small number of segments could be produced in our scenario, and discuss alternative hypotheses for the origin of multipartite viruses with more than four segments.",,"['Iranzo, Jaime', 'Manrubia, Susanna C.']",,,,
,PMC,Synthesis and Biological Properties of C-2 Triazolylinosine Derivatives,http://dx.doi.org/10.1021/jo300628y,PMC3427785,,,"[Image: see text] O(6)-(Benzotriazol-1H-yl)guanosine and its 2′-deoxy analogue are readily converted to the O(6)-allyl derivatives that upon diazotization with t-BuONO and TMS-N(3) yield the C-2 azido derivatives. We have previously analyzed the solvent-dependent azide•tetrazole equilibrium of C-6 azidopurine nucleosides, and in contrast to these, the O(6)-allyl C-2 azido nucleosides appear to exist predominantly in the azido form, relatively independent of solvent polarity. In the presently described cases, the tetrazole appears to be very minor. Consistent with the presence of the azido functionality, each neat C-2 azide displayed a prominent IR band at 2126–2130 cm(−1). A screen of conditions for the ligation of the azido nucleosides with alkynes showed that CuCl in t-BuOH/H(2)O is optimal, yielding C-2 1,2,3-triazolyl nucleosides in 70–82% yields. Removal of the silyl groups with Et(3)N•3HF followed by deallylation with PhSO(2)Na/Pd(PPh(3))(4) gave the C-2 triazolylinosine nucleosides. In a continued demonstration of the versatility of O(6)-(benzotriazol-1H-yl)purine nucleosides, one C-2 triazolylinosine derivative was converted to two adenosine analogues via these intermediates, under mild conditions. Products were desilylated for biological assays. The two C-2 triazolyl adenosine analogues demonstrated pronounced antiproliferative activity in human ovarian and colorectal carcinoma cell cultures. When evaluated for antiviral activity against a broad spectrum of DNA and RNA viruses, some of the C-2 triazolylinosine derivatives showed modest inhibitory activity against cytomegalovirus.",,"['Lakshman, Mahesh K.', 'Kumar, Amit', 'Balachandran, Raghavan', 'Day, Billy W.', 'Andrei, Graciela', 'Snoeck, Robert', 'Balzarini, Jan']",,,,
,PMC,Virus-Like Particle-Induced Protection Against MRSA Pneumonia Is Dependent on IL-13 and Enhancement of Phagocyte Function,http://dx.doi.org/10.1016/j.ajpath.2012.03.018,PMC3388150,,,"The importance of the priming of the lung environment by past infections is being increasingly recognized. Exposure to any given antigen can either improve or worsen the outcome of subsequent lung infections, depending on the immunological history of the host. Thus, an ability to impart transient alterations in the lung environment in anticipation of future insult could provide an important novel therapy for emerging infectious diseases. In this study, we show that nasal administration of virus-like particles (VLPs) before, or immediately after, lethal challenge with methicillin-resistant Staphylococcus aureus (MRSA) of mice i) ensures complete recovery from lung infection and near absolute clearance of bacteria within 12 hours of challenge, ii) reduces host response-induced lung tissue damage, iii) promotes recruitment and efficient bacterial clearance by neutrophils and CD11c(+) cells, and iv) protects macrophages from MRSA-induced necrosis. VLP-mediated protection against MRSA relied on innate immunity. Complete recovery occurred in VLP-dosed mice with severe combined immunodeficiency, but not in wild-type mice depleted of either Ly6G(+) or CD11c(+) cells. Early IL-13 production associated with VLP-induced CD11c(+) cells was essential for VLP-induced protection. These results indicate that VLP-induced alteration of the lung environment protects the host from lethal MRSA pneumonia by enhancing phagocyte recruitment and killing and by reducing inflammation-induced tissue damage via IL-13–dependent mechanisms.",,"['Rynda-Apple, Agnieszka', 'Dobrinen, Erin', 'McAlpine, Mark', 'Read, Amanda', 'Harmsen, Ann', 'Richert, Laura E.', 'Calverley, Matthew', 'Pallister, Kyler', 'Voyich, Jovanka', 'Wiley, James A.', 'Johnson, Ben', 'Young, Mark', 'Douglas, Trevor', 'Harmsen, Allen G.']",,,,
,PMC,Meditation or Exercise for Preventing Acute Respiratory Infection: A Randomized Controlled Trial,http://dx.doi.org/10.1370/afm.1376,PMC3392293,,,"PURPOSE: This study was designed to evaluate potential preventive effects of meditation or exercise on incidence, duration, and severity of acute respiratory infection (ARI) illness. METHODS: Community-recruited adults aged 50 years and older were randomized to 1 of 3 study groups: 8-week training in mindfulness meditation, matched 8-week training in moderate-intensity sustained exercise, or observational control. The primary outcome was area-under-the-curve global illness severity during a single cold and influenza season, using the Wisconsin Upper Respiratory Symptom Survey (WURSS-24) to assess severity. Health care visits and days of missed work were counted. Nasal wash collected during ARI illness was assayed for neutrophils, interleukin-8, and viral nucleic acid. RESULTS: Of 154 adults randomized into the study, 149 completed the trial (82% female, 94% white, mean age 59.3 ± 6.6 years). There were 27 ARI episodes and 257 days of ARI illness in the meditation group (n = 51), 26 episodes and 241 illness days in the exercise group (n = 47), and 40 episodes and 453 days in the control group (n = 51). Mean global severity was 144 for meditation, 248 for exercise, and 358 for control. Compared with control, global severity was significantly lower for meditation (P = .004). Both global severity and total days of illness (duration) trended toward being lower for the exercise group (P=.16 and P=.032, respectively), as did illness duration for the meditation group (P=.034). Adjusting for covariates using zero-inflated multivariate regression models gave similar results. There were 67 ARI-related days of-work missed in the control group, 32 in the exercise group (P = .041), and 16 in the meditation group (P <.001). Health care visits did not differ significantly. Viruses were identified in 54% of samples from meditation, 42% from exercise, and 54% from control groups. Neutrophil count and interleukin-8 levels were similar among intervention groups. CONCLUSIONS: Training in meditation or exercise may be effective in reducing ARI illness burden.",,"['Barrett, Bruce', 'Hayney, Mary S.', 'Muller, Daniel', 'Rakel, David', 'Ward, Ann', 'Obasi, Chidi N.', 'Brown, Roger', 'Zhang, Zhengjun', 'Zgierska, Aleksandra', 'Gern, James', 'West, Rebecca', 'Ewers, Tola', 'Barlow, Shari', 'Gassman, Michele', 'Coe, Christopher L.']",,,,
,PMC,Antiviral Effects of Small Interfering RNA Simultaneously Inducing RNA Interference and Type 1 Interferon in Coxsackievirus Myocarditis,http://dx.doi.org/10.1128/AAC.06050-12,PMC3393429,,,"Antiviral therapeutics are currently unavailable for treatment of coxsackievirus B3, which can cause life-threatening myocarditis. A modified small interfering RNA (siRNA) containing 5′-triphosphate, 3p-siRNA, was shown to induce RNA interference and interferon activation. We aimed to develop a potent antiviral treatment using CVB3-specific 3p-siRNA and to understand its underlying mechanisms. Virus-specific 3p-siRNA was superior to both conventional virus-specific siRNA with an empty hydroxyl group at the 5′ end (OH-siRNA) and nonspecific 3p-siRNA in decreasing viral replication and subsequent cytotoxicity. A single administration of 3p-siRNA dramatically attenuated virus-associated pathological symptoms in mice with no signs of toxicity, and their body weights eventually reached the normal range. Myocardial inflammation and fibrosis were rare, and virus production was greatly reduced. A nonspecific 3p-siRNA showed relatively less protective effect under identical conditions, and a virus-specific OH-siRNA showed no protective effects. We confirmed that virus-specific 3p-siRNA simultaneously activated target-specific gene silencing and type I interferon signaling. We provide a clear proof of concept that coxsackievirus B3-specific 3p-siRNA has 2 distinct modes of action, which significantly enhance antiviral activities with minimal organ damage. This is the first direct demonstration of improved antiviral effects with an immunostimulatory virus-specific siRNA in coxsackievirus myocarditis, and this method could be applied to many virus-related diseases.",,"['Ahn, Jeonghyun', 'Ko, Ara', 'Jun, Eun Jung', 'Won, Minah', 'Kim, Yoo Kyum', 'Ju, Eun-Seon', 'Jeon, Eun Seok', 'Lee, Heuiran']",,,,
,PMC,Cyclophilin Involvement in the Replication of Hepatitis C Virus and Other Viruses,http://dx.doi.org/10.1515/hsz-2012-0151,PMC6650638,,,"In recent months there has been a wealth of promising clinical data suggesting that a more effective treatment regimen, and potentially a cure, for hepatitis C virus (HCV) infection is close at hand. Leading this push are direct acting antivirals (DAAs), currently comprised of inhibitors that target the HCV protease NS3, viral polymerase NS5B and the nonstructural protein NS5A. In combination with one another, along with the traditional standard of care ribavirin and PEGylated-IFNα, these compounds have proven to afford tremendous efficacy to treatment-naïve patients, as well as to prior non-responders. Nevertheless, by targeting viral components the possibility of selecting for breakthrough and treatment-resistant virus strains remains a concern. Host-targeting antivirals (HTAs) are a distinct class of anti-HCV compounds that is emerging as a complementary set of tools to combat the disease. Cyclophilin (Cyp) inhibitors are one such group in this category. In contrast to DAAs, Cyp inhibitors target a host protein, CypA, and have also demonstrated remarkable antiviral efficiency in clinical trials, without the generation of viral escape mutants. This review serves to summarize the current literature on cyclophilins and their relationship to the HCV viral life cycle, as well as other viruses.",,"['Baugh, James', 'Gallay, Philippe']",,,,
,PMC,"Laboratory test descriptions for bovine respiratory disease diagnosis and their strengths and weaknesses: Gold standards for diagnosis, do they exist?",,PMC3377458,,,"The diagnosis of bovine respiratory diseases (BRD) poses significant challenges to the clinician as there are numerous infectious etiologies, operating singly or most often in combination. Clinical signs alone may not be diagnostic and the diagnostic laboratory is often used to assist the clinician. Recently many molecular-based tests have been taken from the research laboratory to the veterinary diagnostic laboratory. This review describes the “traditional tests” and several “molecular tests” and discusses the benefits and limitations of the tests and their interpretation. Clinicians should consult with their diagnostic laboratory regarding the interpretation of the test results. The rate of development and use of molecular diagnostic tests have outpaced validation, standardization, and standards for interpretation relative to their use in BRD diagnostics.",,"['Fulton, Robert W.', 'Confer, Anthony W.']",,,,
,PMC,Comparative Evaluation of Two Hemagglutinating Encephalomyelitis Coronavirus Vaccine Candidates in Mice,http://dx.doi.org/10.1128/CVI.05716-12,PMC3393371,,,"Porcine hemagglutinating encephalomyelitis (PHE) is caused by the coronavirus hemagglutinating encephalomyelitis virus (PHE-CoV), and the recent, rapid spread of PHE-CoV in piglets from many countries emphasizes the urgent need for a PHE-CoV vaccine. Here we use a murine model for evaluation of the induction of humoral and cellular immune responses by inactivated and PHE-CoV DNA vaccines in order to define the immune correlates for protection against PHE-CoV. The inactivated vaccine was composed of purified PHE-CoV and aluminum hydroxide gel (alum), which was chosen as an adjuvant because of its long history of safety for human use. The PHE-CoV DNA vaccine was constructed by subcloning the S1 gene of PHE-CoV into the pVAX1 vector to create the recombinant plasmid pV-S1. Our results showed that the inactivated PHE-CoV vaccine (IPV) elicited a high level of humoral immunity, resulting in good protection efficacy against PHE-CoV challenge. The IPV induced the IgG1 subclass of serum antibodies and expression of the cytokine interleukin-4 (IL-4), suggesting that the IPV generated a predominantly Th2-type immune response. The DNA vaccine was found to mediate primarily a cellular immune response with high levels of IgG2a and the cytokines IL-2 and gamma interferon (IFN-γ). However, mice that were vaccinated twice with the DNA vaccine and boosted with the IPV could mount a sufficient neutralizing antibody response against live PHE-CoV, with little variation in IgG1 and IgG2a levels, and showed high levels of IL-2 and IL-4. This response may activate both B and T cells to mount a specific humoral and cellular immune response that could, in turn, elicit a phagocyte-mediated defense against PHE-CoV infections to achieve viral clearance.",,"['Chen, Keyan', 'Zhao, Kui', 'He, Wenqi', 'Gao, Wei', 'Zhao, Chuanbo', 'Wang, Li', 'Pan, Wei', 'Song, Deguang', 'Wang, Chengli', 'Gao, Feng']",,,,
,PMC,High Titer and Avidity of Nonneutralizing Antibodies against Influenza Vaccine Antigen Are Associated with Severe Influenza,http://dx.doi.org/10.1128/CVI.00081-12,PMC3393364,,,"The importance of neutralizing antibody in protection against influenza virus is well established, but the role of the early antibody response during the initial stage of infection in affecting the severity of disease is unknown. The 2009 influenza pandemic provided a unique opportunity for study because most patients lacked preexisting neutralizing antibody. In this study, we compared the antibody responses of 52 patients with severe or mild disease, using sera collected at admission. A microneutralization (MN) assay was used to detect neutralizing antibody. We also developed an enzyme-linked immunosorbent assay (ELISA) which detects both neutralizing and nonneutralizing antibodies against viral antigens from a split-virion inactivated monovalent influenza virus vaccine. While the MN titers were not significantly different between the two groups (P = 0.764), the ELISA titer and ELISA/MN titer ratio were significantly higher for patients with severe disease than for those with mild disease (P = 0.004 and P = 0.011, respectively). This finding suggested that in patients with severe disease, a larger proportion of serum antibodies were antibodies with no detectable neutralizing activity. The antibody avidity was also significantly higher in patients with severe disease than in those with mild disease (P < 0.05). Among patients with severe disease, those who required positive pressure ventilation (PPV) had significantly higher ELISA titers than those who did not require PPV (P < 0.05). Multivariate analysis showed that the ELISA titer and antibody avidity were independently associated with severe disease. Higher titers of nonneutralizing antibody with higher avidity at the early stage of influenza virus infection may be associated with worse clinical severity and poorer outcomes.",,"['To, Kelvin K. W.', 'Zhang, Anna J. X.', 'Hung, Ivan F. N.', 'Xu, Ting', 'Ip, Whitney C. T.', 'Wong, Rebecca T. Y.', 'Ng, Joseph C. K.', 'Chan, Jasper F. W.', 'Chan, Kwok-Hung', 'Yuen, Kwok-Yung']",,,,
,PMC,Lack of Interference with Immunogenicity of a Chimeric Alphavirus Replicon Particle-Based Influenza Vaccine by Preexisting Antivector Immunity,http://dx.doi.org/10.1128/CVI.00031-12,PMC3393363,,,"Antivector immunity has been recognized as a potential caveat of using virus-based vaccines. In the present study, an alphavirus-based replicon particle vaccine platform, which has demonstrated robust immunogenicity in animal models, was tested for effects of antivector immunity on immunogenicity against hemagglutinin of influenza virus as a target antigen and efficacy for protection against lethal challenge with the virus. Chimeric alphavirus-based replicon particles, comprising Venezuelan equine encephalitis virus nonstructural and Sindbis virus structural components, induced efficient protective antibody responses, which were not adversely influenced after multiple immunizations with the same vector expressing various antigens.",,"['Uematsu, Yasushi', 'Vajdy, Michael', 'Lian, Ying', 'Perri, Silvia', 'Greer, Catherine E.', 'Legg, Harold S.', 'Galli, Grazia', 'Saletti, Giulietta', 'Otten, Gillis R.', 'Rappuoli, Rino', 'Barnett, Susan W.', 'Polo, John M.']",,,,
,PMC,Bugs and Drugs: Oncolytic Virotherapy in Combination with Chemotherapy,,PMC4373447,,,"Single agent therapies are rarely successful in treating cancer, particularly at metastatic or end stages, and survival rates with monotherapies alone are generally poor. The combination of multiple therapies to treat cancer has already driven significant improvements in the standard of care treatments for many types of cancers. The first combination treatments exploited for cancer therapy involved the use of several cytotoxic chemotherapy agents. Later, with the development of more targeted agents, the use of novel, less toxic drugs, in combination with the more classic cytotoxic drugs has proven advantageous for certain cancer types. Recently, the combination of oncolytic virotherapy with chemotherapy has shown that the use of these two therapies with very distinct anti-tumor mechanisms may also lead to synergistic interactions that ultimately result in increased therapeutic effects not achievable by either therapy alone. The mechanisms of synergy between oncolytic viruses (OVs) and chemotherapeutic agents are just starting to be elucidated. It is evident, however, that the success of these OV-drug combinations depends greatly on the particular O V, the drug(s) selected, and the cancer type targeted. This review summarizes the different OV-drug combinations investigated to date, including the use of second generation armed OVs, which have been studied with the specific purpose of generating synergistic interactions with particular chemotherapy agents. The known mechanisms of synergy between these OV-drug combinations are also summarized. The importance of further investigating these mechanisms of synergy will be critical in order to maximize the therapeutic efficacy of OV-drug combination therapies in the future.",,"['Wennier, Sonia Tusell', 'Liu, Jia', 'McFadden, Grant']",,,,
,PMC,Cholera Modeling: Challenges to Quantitative Analysis and Predicting the Impact of Interventions,http://dx.doi.org/10.1097/EDE.0b013e3182572581,PMC3380087,,,"Several mathematical models of epidemic cholera have recently been proposed in response to outbreaks in Zimbabwe and Haiti. These models aim to estimate the dynamics of cholera transmission and the impact of possible interventions, with a goal of providing guidance to policy-makers in deciding among alternative courses of action, including vaccination, provision of clean water, and antibiotics. Here we discuss concerns about model misspecification, parameter uncertainty, and spatial heterogeneity intrinsic to models for cholera. We argue for caution in interpreting quantitative predictions, particularly predictions of the effectiveness of interventions. We specify sensitivity analyses that would be necessary to improve confidence in model-based quantitative prediction, and suggest types of monitoring in future epidemic settings that would improve analysis and prediction.",,"['Grad, Yonatan H.', 'Miller, Joel C.', 'Lipsitch, Marc']",,,,
,PMC,Enhanced humoral and HLA-A2-restricted dengue virus-specific T-cell responses in humanized BLT NSG mice,http://dx.doi.org/10.1111/j.1365-2567.2012.03585.x,PMC3385033,,,"Dengue is a mosquito-borne viral disease of humans, and animal models that recapitulate human immune responses or dengue pathogenesis are needed to understand the pathogenesis of the disease. We recently described an animal model for dengue virus (DENV) infection using humanized NOD-scid IL2rγ(null) mice (NSG) engrafted with cord blood haematopoietic stem cells. We sought to further improve this model by co-transplantation of human fetal thymus and liver tissues into NSG (BLT-NSG) mice. Enhanced DENV-specific antibody titres were found in the sera of BLT-NSG mice compared with human cord blood haematopoietic stem cell-engrafted NSG mice. Furthermore, B cells generated during the acute phase and in memory from splenocytes of immunized BLT-NSG mice secreted DENV-specific IgM antibodies with neutralizing activity. Human T cells in engrafted BLT-NSG mice secreted interferon-γ in response to overlapping DENV peptide pools and HLA-A2 restricted peptides. The BLT-NSG mice will allow assessment of human immune responses to DENV vaccines and the effects of previous immunity on subsequent DENV infections.",,"['Jaiswal, Smita', 'Pazoles, Pamela', 'Woda, Marcia', 'Shultz, Leonard D', 'Greiner, Dale L', 'Brehm, Michael A', 'Mathew, Anuja']",,,,
,PMC,Comparison of the Luminex xTAG RVP Fast Assay and the Idaho Technology FilmArray RP Assay for Detection of Respiratory Viruses in Pediatric Patients at a Cancer Hospital,http://dx.doi.org/10.1128/JCM.06186-11,PMC3405573,,,"Respiratory viruses are increasingly recognized as serious causes of morbidity and mortality in immunocompromised patients. The rapid and sensitive detection of respiratory viruses is essential for the early diagnosis and administration of appropriate antiviral therapy, as well as for the effective implementation of infection control measures. We compared the performance of two commercial assays, xTAG RVP Fast (Luminex Diagnostics, Toronto, Canada) and FilmArray RVP (FA RVP; Idaho Technology, Salt Lake City, UT), in pediatric patients at Memorial Sloan-Kettering Cancer Center. These assays detect the following viruses: respiratory syncytial virus; influenza A and B viruses; parainfluenza viruses 1, 2, 3, and 4; human metapneumovirus; adenovirus; enterovirus-rhinovirus; coronaviruses NL63, HKU1, 229E, and OC43; and bocavirus. We tested a total of 358 respiratory specimens from 173 pediatric patients previously tested by direct fluorescence assay (DFA) and viral culture. The overall detection rate (number of positive specimens/total specimens) for viruses tested by all methods was 24% for DFA/culture, 45% for xTAG RVP Fast, and 51% for FA RVP. The agreement between the two multiplex assays was 84.5%, and the difference in detection rate was statistically significant (P < 0.0001). Overall, the FA RVP assay was more sensitive than the xTAG RVP Fast assay and had a turnaround time of approximately 1 h. The sensitivity, simplicity, and random-access platform make FA RVP an excellent choice for laboratory on-demand service with low to medium volume.",,"['Babady, N. Esther', 'Mead, Peter', 'Stiles, Jeffrey', 'Brennan, Carrie', 'Li, Haijing', 'Shuptar, Susan', 'Stratton, Charles W.', 'Tang, Yi-Wei', 'Kamboj, Mini']",,,,
,PMC,The human side of influenza,http://dx.doi.org/10.1189/jlb.1011506,PMC3382310,,,"A clear understanding of immunity in individuals infected with influenza virus is critical for the design of effective vaccination and treatment strategies. Whereas myriad studies have teased apart innate and adaptive immune responses to influenza infection in murine models, much less is known about human immunity as a result of the ethical and technical constraints of human research. Still, these murine studies have provided important insights into the critical correlates of protection and pathogenicity in human infection and helped direct the human studies that have been conducted. Here, we examine and review the current literature on immunity in humans infected with influenza virus, noting evidence offered by select murine studies and suggesting directions in which future research is most warranted.",,"['Oshansky, Christine M.', 'Thomas, Paul G.']",,,,
,PMC,Mutations in the GM1 Binding Site of Simian Virus 40 VP1 Alter Receptor Usage and Cell Tropism,http://dx.doi.org/10.1128/JVI.00371-12,PMC3416316,,,"Polyomaviruses are nonenveloped viruses with capsids composed primarily of 72 pentamers of the viral VP1 protein, which forms the outer shell of the capsid and binds to cell surface oligosaccharide receptors. Highly conserved VP1 proteins from closely related polyomaviruses recognize different oligosaccharides. To determine whether amino acid changes restricted to the oligosaccharide binding site are sufficient to determine receptor specificity and how changes in receptor usage affect tropism, we studied the primate polyomavirus simian virus 40 (SV40), which uses the ganglioside GM1 as a receptor that mediates cell binding and entry. Here, we used two sequential genetic screens to isolate and characterize viable SV40 mutants with mutations in the VP1 GM1 binding site. Two of these mutants were completely resistant to GM1 neutralization, were no longer stimulated by incorporation of GM1 into cell membranes, and were unable to bind to GM1 on the cell surface. In addition, these mutant viruses displayed an infection defect in monkey cells with high levels of cell surface GM1. Interestingly, one mutant infected cells with low cell surface GM1 more efficiently than wild-type virus, apparently by utilizing a different ganglioside receptor. Our results indicate that a small number of mutations in the GM1 binding site are sufficient to alter ganglioside usage and change tropism, and they suggest that VP1 divergence is driven primarily by a requirement to accommodate specific receptors. In addition, our results suggest that GM1 binding is required for vacuole formation in permissive monkey CV-1 cells. Further study of these mutants will provide new insight into polyomavirus entry, pathogenesis, and evolution.",,"['Magaldi, Thomas G.', 'Buch, Michael H. C.', 'Murata, Haruhiko', 'Erickson, Kimberly D.', 'Neu, Ursula', 'Garcea, Robert L.', 'Peden, Keith', 'Stehle, Thilo', 'DiMaio, Daniel']",,,,
,PMC,RNA Structural Elements Determine Frequency and Sites of Nonhomologous Recombination in an Animal Plus-Strand RNA Virus,http://dx.doi.org/10.1128/JVI.00864-12,PMC3416315,,,"For highly variable RNA viruses, RNA recombination significantly contributes to genetic variations which may lead to changes of virulence, adaptation to new hosts, escape from the host immune response, and emergence of new infectious agents. Using a system based on transfection of cells with synthetic nonreplicable subgenomic transcripts derived from bovine viral diarrhea virus (family Flaviviridae), the existence of a replication-independent mechanism of RNA recombination, in addition to the commonly accepted replicative copy-choice recombination, has been previously proven (A. Gallei et al., J. Virol. 78:6271–6281, 2004). To identify RNA signals involved in efficient joining of RNA molecules, RNA recombination in living cells was targeted to the 3′ nontranslated region. Molecular characterization of 40 independently emerged recombinant viruses revealed that the majority of recombination sites are located in single-stranded regions of the RNA molecules. Furthermore, the results of this study showed that the frequency of RNA recombination directly correlated with the RNA amounts of both recombination partners. The frequency can be strongly increased by modification of the 5′ triphosphates and 3′ hydroxyls of the recombining RNA molecules to 5′ hydroxyl and 3′ monophosphoryl ends, respectively. Analysis of recombinants that emerged after transfection with such modified RNA molecules revealed a complete integration and efficient end-to-end joining of the recombination partner(s) in at least 80% of recombinants, while unmodified RNA molecules recombined exclusively at internal positions. These results are in line with the hypothesis that endoribonucleolytic cleavage and a subsequent ligation reaction can cause RNA recombination.",,"['Austermann-Busch, Sophia', 'Becher, Paul']",,,,
,PMC,The IE180 Protein of Pseudorabies Virus Suppresses Phosphorylation of Translation Initiation Factor eIF2α,http://dx.doi.org/10.1128/JVI.06929-11,PMC3416314,,,"We have previously shown that the porcine alphaherpesvirus pseudorabies virus (PRV) efficiently interferes with phosphorylation of the eukaryotic translation initiation factor eIF2α. Inhibition of phosphorylation of eIF2α has been reported earlier for the closely related alphaherpesvirus herpes simplex virus 1 (HSV-1) through its ICP34.5 and US11 proteins. PRV, however, does not encode an ICP34.5 or US11 orthologue. Assays using cycloheximide, UV-inactivated PRV, or phosphonoacetic acid (PAA) showed that de novo expression of one or more (immediate) early viral protein(s) is required for interference with eIF2α phosphorylation. In line with this, a time course assay showed that eIF2α phosphorylation was abolished within 2 h after PRV inoculation. PRV encodes only one immediate-early protein, IE180, the orthologue of HSV-1 ICP4. As reported earlier, a combinational treatment of cells with cycloheximide and actinomycin D allowed expression of IE180 without detectable expression of the US3 early protein in PRV-infected cells. This led to a substantial reduction in eIF2α phosphorylation levels, indicative for an involvement of IE180. In support of this, transfection of IE180 also potently reduced eIF2α phosphorylation. IE180-mediated interference with eIF2α phosphorylation was not cell type dependent, as it occurred both in rat neuronal 50B11 cells and in swine testicle cells. Inhibition of the cellular phosphatase PP1 impaired PRV-mediated interference with eIF2α phosphorylation, indicating that PP1 is involved in this process. In conclusion, the immediate-early IE180 protein of PRV has the previously uncharacterized ability to suppress phosphorylation levels of the eukaryotic translation initiation factor eIF2α.",,"['Van Opdenbosch, N.', 'Van den Broeke, C.', 'De Regge, N.', 'Tabarés, E.', 'Favoreel, H. W.']",,,,
,PMC,Crystal Structure of the Superfamily 1 Helicase from Tomato Mosaic Virus,http://dx.doi.org/10.1128/JVI.00118-12,PMC3416300,,,"The genomes of the Tomato mosaic virus and many other plant and animal positive-strand RNA viruses of agronomic and medical importance encode superfamily 1 helicases. Although helicases play important roles in viral replication, the crystal structures of viral superfamily 1 helicases have not been determined. Here, we report the crystal structure of a fragment (S666 to Q1116) of the replication protein from Tomato mosaic virus. The structure reveals a novel N-terminal domain tightly associated with a helicase core. The helicase core contains two RecA-like α/β domains without any of the accessory domain insertions that are found in other superfamily 1 helicases. The N-terminal domain contains a flexible loop, a long α-helix, and an antiparallel six-stranded β-sheet. On the basis of the structure, we constructed deletion mutants of the S666-to-Q1116 fragment and performed split-ubiquitin-based interaction assays in Saccharomyces cerevisiae with TOM1 and ARL8, host proteins that are essential for tomato mosaic virus RNA replication. The results suggested that both TOM1 and ARL8 interact with the long α-helix in the N-terminal domain and that TOM1 also interacts with the helicase core. Prediction of secondary structures in other viral superfamily 1 helicases and comparison of those structures with the S666-to-Q1116 structure suggested that these helicases have a similar fold. Our results provide a structural basis of viral superfamily 1 helicases.",,"['Nishikiori, Masaki', 'Sugiyama, Shigeru', 'Xiang, Hongyu', 'Niiyama, Mayumi', 'Ishibashi, Kazuhiro', 'Inoue, Tsuyoshi', 'Ishikawa, Masayuki', 'Matsumura, Hiroyoshi', 'Katoh, Etsuko']",,,,
,PMC,A Human Coronavirus Responsible for the Common Cold Massively Kills Dendritic Cells but Not Monocytes,http://dx.doi.org/10.1128/JVI.00269-12,PMC3416289,,,"Human coronaviruses are associated with upper respiratory tract infections that occasionally spread to the lungs and other organs. Although airway epithelial cells represent an important target for infection, the respiratory epithelium is also composed of an elaborate network of dendritic cells (DCs) that are essential sentinels of the immune system, sensing pathogens and presenting foreign antigens to T lymphocytes. In this report, we show that in vitro infection by human coronavirus 229E (HCoV-229E) induces massive cytopathic effects in DCs, including the formation of large syncytia and cell death within only few hours. In contrast, monocytes are much more resistant to infection and cytopathic effects despite similar expression levels of CD13, the membrane receptor for HCoV-229E. While the differentiation of monocytes into DCs in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4 requires 5 days, only 24 h are sufficient for these cytokines to sensitize monocytes to cell death and cytopathic effects when infected by HCoV-229E. Cell death induced by HCoV-229E is independent of TRAIL, FasL, tumor necrosis factor alpha, and caspase activity, indicating that viral replication is directly responsible for the observed cytopathic effects. The consequence of DC death at the early stage of HCoV-229E infection may have an impact on the early control of viral dissemination and on the establishment of long-lasting immune memory, since people can be reinfected multiple times by HCoV-229E.",,"['Mesel-Lemoine, Mariana', 'Millet, Jean', 'Vidalain, Pierre-Olivier', 'Law, Helen', 'Vabret, Astrid', 'Lorin, Valérie', 'Escriou, Nicolas', 'Albert, Matthew L.', 'Nal, Béatrice', 'Tangy, Frédéric']",,,,
,PMC,Porcine Reproductive and Respiratory Syndrome Virus Induces Interleukin-15 through the NF-κB Signaling Pathway,http://dx.doi.org/10.1128/JVI.00177-12,PMC3416278,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) mainly infects macrophages/dendritic cells and modulates cytokine expression in these cells. Interleukin-15 (IL-15) is a pleiotropic cytokine involved in wide range of biological activities. It has been shown to be essential for the generation, activation, and proliferation of NK and NKT cells and for the survival and activation of CD8(+) effector and memory T cells. In this study, we discovered that PRRSV infection upregulated IL-15 production at both the mRNA and protein levels in porcine alveolar macrophages (PAMs), blood monocyte-derived macrophages (BMo), and monocyte-derived dendritic cells (DCs). We subsequently demonstrated that the NF-κB signaling pathway was essential for PRRSV infection-induced IL-15 production. First, addition of an NF-κB inhibitor drastically reduced PRRSV infection-induced IL-15 production. We then found that NF-κB was indeed activated upon PRRSV infection, as evidenced by IκB phosphorylation and degradation. Moreover, we revealed an NF-κB binding motif in the cloned porcine IL-15 (pIL-15) promoter, deletion of which abrogated the pIL-15 promoter activity in PRRSV-infected alveolar macrophages. In addition, we demonstrated that PRRSV nucleocapsid (N) protein had the ability to induce IL-15 production in porcine alveolar macrophage cell line CRL2843 by transient transfection, which was mediated by its multiple motifs, and it also activated NF-κB. These data indicated that PRRSV infection-induced IL-15 production was likely through PRRSV N protein-mediated NF-κB activation. Our findings provide new insights into the molecular mechanisms underling the IL-15 production induced by PRRSV infection.",,"['Fu, Yi', 'Quan, Rong', 'Zhang, Hexiao', 'Hou, Jun', 'Tang, Jun', 'Feng, Wen-hai']",,,,
,PMC,Pulmonary sequelae in a patient recovered from swine flu,http://dx.doi.org/10.4103/0970-2113.99118,PMC3424870,22919170,CC BY-NC-SA,"The pandemic of swine flu (H1N1) influenza spread to involve the whole world rapidly. Many patients manifested a mild clinical illness but some developed pneumonia and respiratory failure. High mortality was observed in patients with severe disease. Among survivors, studies are limited. Ground-glass opacities on a high-resolution computerized tomography scan and reduced diffusion capacity were noted after 3 months in a study. But long-term complications in patients with swine flu pneumonia have not been studied well. We are presenting an unusual case of swine flu pneumonia who developed interstitial lung disease after recovery.",2012 Jul-Sep,"['Singh, Virendra', 'Sharma, Bharat Bhushan', 'Patel, Vivek']",Lung India,,,
,PMC,Viral Load and Acute Otitis Media Development after Human Metapneumovirus Upper Respiratory Tract Infection,http://dx.doi.org/10.1097/INF.0b013e3182539d92,PMC3375353,,,"The role of human metapneumovirus (hMPV) in acute otitis media (AOM) complicating upper respiratory tract infection (URI) was studied. Nasopharyngeal specimens from 700 URI episodes in 200 children were evaluated; 47 (7%) were positive for hMPV, 25 (3.6%) with hMPV as the only virus. Overall, 24% of URI episodes with hMPV only were complicated by AOM, which was the lowest rate compared with other respiratory viruses. hMPV viral load was significantly higher in children with fever, but there was no difference in viral load in children with hMPV positive URI with or without AOM complication.",,"['Nokso-Koivisto, Johanna', 'Pyles, Richard B.', 'Miller, Aaron L.', 'Patel, Janak A', 'Loeffelholz, Michael', 'Chonmaitree, Tasnee']",,,,
,PMC,Multieffector-Functional Immune Responses of HMBPP-Specific Vγ2Vδ2 T Cells in Nonhuman Primates Inoculated with Listeria monocytogenes ΔactA prfA*,http://dx.doi.org/10.4049/jimmunol.1200641,PMC3412419,,,"Although Listeria monocytogenes can induce systemic infection causing spontaneous abortion, septicemia, and meningitis, studies have not been performed to investigate human anti-L. monocytogenes immune responses, including those of Ag-specific Vγ2Vδ2 T cells, a dominant human γδ T cell subset. L. monocytogenes is the only pathogen known to possess both the mevalonate and non-mevalonate isoprenoid biosynthesis pathways that produce metabolic phosphates or phosphoantigens activating human Vγ2Vδ2 T cells, making it interesting to explore in vivo anti-L. monocytogenes immune responses of Vγ2Vδ2 T cells. In this study, we demonstrated that subclinical systemic L. monocytogenes infection of rhesus macaques via parenteral inoculation or vaccination with an attenuated Listeria strain induced multieffector-functional immune responses of phosphoantigen-specific Vγ2Vδ2 T cells. Subclinical systemic infection and reinfection with attenuated L. monocytogenes uncovered the ability of Vγ2Vδ2 T cells to mount expansion and adaptive or recall-like expansion. Expanded Vγ2Vδ2 T cells could traffic to and accumulate in the pulmonary compartment and intestinal mucosa. Expanded Vγ2Vδ2 T cells could evolve into effector cells producing IFN-γ, TNF-α, IL-4, IL-17, or perforin after L. monocytogenes infection, and some effector Vγ2Vδ2 T cells could coproduce IL-17 and IFN-γ, IL-4 and IFN-γ, or TNF-α and perforin. Surprisingly, in vivo-expanded Vγ2Vδ2 T effector cells in subclinical L. monocytogenes infection could directly lyse L. monocytogenes-infected target cells and inhibit intracellular L. monocytogenes bacteria. Thus, we present the first demonstration, to our knowledge, of multieffector-functional Vγ2Vδ2 T cell responses against L. monocytogenes.",,"['Ryan-Payseur, Bridgett', 'Frencher, James', 'Shen, Ling', 'Chen, Crystal Y.', 'Huang, Dan', 'Chen, Zheng W.']",,,,
,PMC,Oligodendroglia are limited in type I interferon induction and responsiveness in vivo,http://dx.doi.org/10.1002/glia.22375,PMC3422432,,,"Type I interferons (IFNα/β) provide a primary defense against infection. Nevertheless, the dynamics of IFNα/β induction and responsiveness by central nervous system (CNS) resident cells in vivo in response to viral infections are poorly understood. Mice were infected with a neurotropic coronavirus with tropism for oligodendroglia and microglia to probe innate antiviral responses during acute encephalomyelitis. Expression of genes associated with the IFNα/β pathways were monitored in microglia and oligodendroglia purified from naïve and infected mice by fluorescent activated cell sorting. Compared to microglia, oligodendroglia were characterized by low basal expression of mRNA encoding viral RNA sensing pattern recognition receptors (PRRs), IFNα/β receptor chains, interferon sensitive genes (ISG), as well as kinases and transcription factors critical in IFNα/β signaling. Although PRRs and ISGs were upregulated by infection in both cell types, the repertoire and absolute mRNA levels were more limited in oligodendroglia. Furthermore, although oligodendroglia harbored higher levels of viral RNA compared to microglia, Ifnα/β was only induced in microglia. Stimulation with the double stranded RNA analogue poly I:C also failed to induce Ifnα/β in oligodendroglia, and resulted in reduced and delayed induction of ISGs compared to microglia. The limited antiviral response by oligodendroglia was associated with a high threshold for upregulation of Ikkε and Irf7 transcripts, both central to amplifying IFNα/β responses. Overall, these data reveal that oligodendroglia from the adult CNS are poor sensors of viral infection and suggest they require exogenous IFNα/β to establish an antiviral state.",,"['Kapil, Parul', 'Butchi, Niranjan B.', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.']",,,,
,PMC,A review of the pathology and treatment of canine respiratory infections,http://dx.doi.org/10.2147/VMRR.S25021,PMC6065594,,,"Numerous infectious agents are responsible for causing primary or secondary respiratory disease in dogs. These agents can cause upper or lower respiratory infections commonly observed in veterinary practices. Clinical signs might vary from mild dyspnea, sneezing, and coughing to severe pneumonia with systemic manifestations. Depending on the etiologic agent, the gross and microscopic changes observed during these infections can be rather unspecific or have highly characteristic patterns. While histopathology and cytology are not always required for diagnosis of respiratory infections, they are often useful for establishing a definitive diagnosis and identifying specific etiologic agents. Research regarding epidemiology, pathogenesis, diagnostics, and clinical manifestations related to these infectious pathogens provides valuable information that has improved treatments and management of the diseases they cause. This review discusses the epidemiology, general clinical characteristics, and pathologic lesions for some of the important viral, bacterial, fungal, and parasitic etiologies of canine respiratory disease.",,"['Vieson, Miranda D', 'Piñeyro, Pablo', 'LeRoith, Tanya']",,,,
,PMC,Genetic variation in BAFF and asthma exacerbations among African American individuals,http://dx.doi.org/10.1016/j.jaci.2012.04.047,PMC3520130,,,A BAFF polymorphism is associated with asthma exacerbations and serum BAFF levels. BAFF expression in vivo increases in natural rhinovirus infection. BAFF may play a role in airway antiviral immunity and impact asthma exacerbation rates.,,"['Kumar, Rajesh', 'Williams, L. Keoki', 'Kato, Atsushi', 'Peterson, Edward L.', 'Favoreto, Silvio', 'Hulse, Katie', 'Wang, Deli', 'Beckman, Kenneth', 'Thyne, Shannon', 'LeNoir, Michael', 'Meade, Kelley', 'Lanfear, David E.', 'Levin, Albert M.', 'Favro, David', 'Yang, James J.', 'Weiss, Kevin', 'Boushey, Homer A.', 'Grammer, Leslie', 'Avila, Pedro C', 'Burchard, Esteban G.', 'Schleimer, Robert']",,,,
,PMC,"Evolution, Safety, and Highly Pathogenic Influenza Viruses",http://dx.doi.org/10.1126/science.1223204,PMC3467308,,,"Experience with influenza has shown that predictions of virus phenotype or fitness from nucleotide sequence are imperfect, and that predicting the timing and course of evolution is extremely difficult. Such uncertainty means that the risk of experiments with mammalian-transmissible, possibly highly virulent influenza viruses remains high even if some aspects of their laboratory biology are reassuring; it also implies limitations on the ability of laboratory observations to guide interpretation of surveillance of strains in the field. Given these considerations, we propose that future experiments with virulent pathogens whose accidental or deliberate release could lead to extensive spread in human populations should be limited by explicit risk-benefit considerations, in the United States and worldwide.",,"['Lipsitch, Marc', 'Plotkin, Joshua B.', 'Simonsen, Lone', 'Bloom, Barry']",,,,
,PMC,Priming T-cell responses with recombinant measles vaccine vector in a heterologous prime-boost setting in non-human primates,http://dx.doi.org/10.1016/j.vaccine.2012.06.029,PMC3425710,,,"Licensed live attenuated virus vaccines capable of expressing transgenes from other pathogens have the potential to reduce the number of childhood immunizations by eliciting robust immunity to multiple pathogens simultaneously. Recombinant attenuated measles virus (rMV) derived from the Edmonston Zagreb vaccine strain was engineered to express simian immunodeficiency virus (SIV) Gag protein for the purpose of evaluating the immunogenicity of rMV as a vaccine vector in rhesus macaques. rMV-Gag immunization alone elicited robust measles-specific humoral and cellular responses, but failed to elicit transgene (Gag)-specific immune responses, following aerosol or intratracheal/intramuscular delivery. However, when administered as a priming vaccine to a heterologous boost with recombinant adenovirus serotype 5 expressing the same transgene, rMV-Gag significantly enhanced Gag-specific T lymphocyte responses following rAd5 immunization. Gag-specific humoral responses were not enhanced, however, which may be due to either the transgene or the vector. Cellular response priming by rMV against the transgene was highly effective even when using a suboptimal dose of rAd5 for the boost. These data demonstrate feasibility of using rMV as a priming component of heterologous prime-boost vaccine regimens for pathogens requiring strong cellular responses.",,"['Bolton, Diane L.', 'Santra, Sampa', 'Swett, Cindy', 'Custers, Jerome', 'Song, Kaimei', 'Balachandran, Harikrishnan', 'Kozlowski, Pamela A.', 'Letvin, Norman', 'Roederer, Mario', 'Radošević, Katarina']",,,,
,PMC,Comparison of nasopharyngeal flocked swabs and nasopharyngeal wash collection methods for respiratory virus detection in hospitalized children using real-time polymerase chain reaction,http://dx.doi.org/10.1016/j.jviromet.2012.06.009,PMC4655598,,,"This paper describes the molecular detection of respiratory viruses from nasopharyngeal flocked swabs (flocked swabs) and nasopharyngeal washes (washes) in a clinical setting. Washes and flocked swabs collected from children < 3 years old hospitalized with a lower respiratory tract infection were tested for parainfluenza virus 1–3, respiratory syncytial virus, influenza A and B and metapneumovirus (Group 1) and adenovirus, rhinovirus and coronavirus (Group 2) using real-time reverse transcriptase PCR (rRT-PCR). A consensuses standard was used to determine sensitivity and compare cycle thresholds (C(T)) of washes and flocked swabs for each virus and group of viruses. Sensitivities ranged from 79 to 89% and 69 to 94% for flocked swabs and washes, respectively, excluding AdV which had a sensitivity of 35% for flocked swabs. When the flocked swabs and washes of Group 1 viruses were collected on the day of admission, the sensitivity of both sample types was 100%. Wash specimens had a lower C(T) value and higher sensitivity than flocked swabs; however there was no statistical difference in the sensitivity of a flocked swab (89%) versus wash (93%) for the detection of Group 1 viruses, particularly when samples were collected on the same day. Flocked swabs may be a useful alternative to washes for detection of respiratory viruses in clinical settings.",,"['DeByle, Carolynn', 'Bulkow, Lisa', 'Miernyk, Karen', 'Chikoyak, Lori', 'Hummel, Kimberlee Boyd', 'Hennessy, Thomas', 'Singleton, Rosalyn']",,,,
,PMC,Chinese hamster ovary cell lines selected for resistance to ebolavirus glycoprotein mediated infection are defective for NPC1 expression,http://dx.doi.org/10.1016/j.virol.2012.05.018,PMC3402687,,,"Ebolavirus causes severe hemorrhagic fever in humans and non-human primates. Entry of ebolavirus is mediated by the viral glycoprotein, GP; however, the required host factors have not been fully elucidated. A screen utilizing a recombinant Vesicular Stomatitis Virus (VSV) encoding Zaire ebolavirus GP identified four Chinese Hamster Ovary (CHO) cell lines resistant to GP-mediated viral entry. Susceptibility to vectors carrying SARS coronavirus S or VSV-G glycoproteins suggests that endocytic and processing pathways utilized by other viruses are intact in these cells. A cathepsin-activated form of the ebolaviral glycoprotein did not overcome the entry restriction, nor did expression of several host factors previously described as important for ebolavirus entry. Conversely, expression of the recently described ebolavirus host entry factor Niemann-Pick Type C1 (NPC1) restored infection. Resistant cells encode distinct mutations in the NPC1 gene, resulting in loss of protein expression. These studies reinforce the importance of NPC1 for ebolavirus entry.",,"['Haines, Kathleen M.', 'Vande Burgt, Nathan H.', 'Francica, Joseph R.', 'Kaletsky, Rachel L.', 'Bates, Paul']",,,,
,PMC,Does genetic diversity limit disease spread in natural host populations?,http://dx.doi.org/10.1038/hdy.2012.33,PMC3464021,,,"It is a commonly held view that genetically homogenous host populations are more vulnerable to infection than genetically diverse populations. The underlying idea, known as the ‘monoculture effect,' is well documented in agricultural studies. Low genetic diversity in the wild can result from bottlenecks (that is, founder effects), biparental inbreeding or self-fertilization, any of which might increase the risk of epidemics. Host genetic diversity could buffer populations against epidemics in nature, but it is not clear how much diversity is required to prevent disease spread. Recent theoretical and empirical studies, particularly in Daphnia populations, have helped to establish that genetic diversity can reduce parasite transmission. Here, we review the present theoretical work and empirical evidence, and we suggest a new focus on finding ‘diversity thresholds.'",,"['King, K C', 'Lively, C M']",,,,
,PMC,Engineering H5N1 avian influenza viruses to study human adaptation,http://dx.doi.org/10.1038/nature11170,PMC3731044,,,"Two studies of H5N1 avian influenza viruses that had been genetically engineered to render them transmissible between ferrets have proved highly controversial. Divergent opinions exist about the importance of these studies of influenza transmission and about potential ‘dual use’ research implications. No consensus has developed yet about how to balance these concerns. After not recommending immediate full publication of earlier, less complete versions of the studies, the United States National Science Advisory Board for Biosecurity subsequently recommended full publication of more complete manuscripts; however, controversy about this and similar research remains.",,"['Morens, David M.', 'Subbarao, Kanta', 'Taubenberger, Jeffery K.']",,,,
,PMC,Novel Viral Vectored Vaccines for the Prevention of Influenza,http://dx.doi.org/10.2119/molmed.2012.00147,PMC3510293,,,"Influenza represents a substantial global healthcare burden, with annual epidemics resulting in 3–5 million cases of severe illness with a significant associated mortality. In addition, the risk of a virulent and lethal influenza pandemic has generated widespread and warranted concern. Currently licensed influenza vaccines are limited in their ability to induce efficacious and long-lasting herd immunity. In addition, and as evidenced by the H1N1 pandemic in 2009, there can be a significant delay between the emergence of a pandemic influenza and an effective, antibody-inducing vaccine. There is, therefore, a continued need for new, efficacious vaccines conferring cross-clade protection—obviating the need for biannual reformulation of seasonal influenza vaccines. Development of such a vaccine would yield enormous health benefits to society and also greatly reduce the associated global healthcare burden. There are a number of alternative influenza vaccine technologies being assessed both preclinically and clinically. In this review we discuss viral vectored vaccines, either recombinant live-attenuated or replication-deficient viruses, which are current lead candidates for inducing efficacious and long-lasting immunity toward influenza viruses. These alternate influenza vaccines offer real promise to deliver viable alternatives to currently deployed vaccines and more importantly may confer long-lasting and universal protection against influenza viral infection.",,"Lambe, Teresa",,,,
,PMC,Mechanisms and Implications of Programmed Translational Frameshifting,http://dx.doi.org/10.1002/wrna.1126,PMC3419312,,,"While ribosomes must maintain translational reading frame in order to translate primary genetic information into polypeptides, cis-acting signals located on mRNAs represent higher order information content that can be used to fine tune gene expression. Classes of signals have been identified that direct a fraction of elongating ribosomes to shift reading frame by one base in the 5′ (−1) or 3′ (+1) direction. This is called programmed ribosomal frameshifting (PRF). Although mechanisms of PRF differ, a common feature is induction of ribosome pausing, which alters kinetic partitioning rates between in-frame and out-of-frame codons at specific “slippery” sequences. Many viruses use PRF to ensure synthesis of the correct ratios of virus-encoded proteins required for proper viral particle assembly and maturation, thus identifying PRF as an attractive target for antiviral therapeutics. In contrast, recent studies indicate that PRF signals may primarily function as mRNA destabilizing elements in cellular mRNAs. These studies suggest that PRF may be used to fine-tune gene expression through mRNA decay pathways. The possible regulation of PRF by non-coding RNAs is also discussed.",,"Dinman, Jonathan D.",,,,
,PMC,Humoral innate immune response and disease,http://dx.doi.org/10.1016/j.clim.2012.06.002,PMC3576926,,,"The humoral innate immune response consists of multiple components, including the naturally occurring antibodies (NAb), pentraxins and the complement and contact cascades. As soluble, plasma components, these innate proteins provide key elements in the prevention and control of disease. However, pathogens and cells with altered self proteins utilize multiple humoral components to evade destruction and promote pathogy. Many studies have examined the relationship between humoral immunity and autoimmune disorders. This review focuses on the interactions between the humoral components and their role in promoting the pathogenesis of bacterial and viral infections and chronic diseases such as atherosclerosis and cancer. Understanding the beneficial and detrimental aspects of the individual components and the interactions between proteins which regulate the innate and adaptive response will provide therapeutic targets for subsequent studies.",,"['Shishido, Stephanie N.', 'Varahan, Sriram', 'Yuan, Kai', 'Li, Xiangdong', 'Fleming, Sherry D.']",,,,
,PMC,Update in Respiratory Infections 2011,http://dx.doi.org/10.1164/rccm.201203-0540UP,PMC5448584,,,,,"['Wunderink, Richard G.', 'Niederman, Michael S.']",,,,
,PMC,Bioluminescence Assay Platform for Selective and Sensitive Detection of Ub/Ubl Proteases,http://dx.doi.org/10.1016/j.bbamcr.2012.06.004,PMC3465522,,,"As the importance of ubiquitylation in certain disease states becomes increasingly apparent, the enzymes responsible for removal of ubiquitin (Ub) from target proteins, deubiquitylases (DUBs), are becoming attractive targets for drug discovery. For rapid identification of compounds that alter DUB function, in vitro assays must be able to provide statistically robust data over a wide dynamic range of both substrate and enzyme concentrations during high throughput screening (HTS). The most established reagents for HTS are Ubs with a quenched fluorophore conjugated to the C-terminus; however, a luciferase-based strategy for detecting DUB activity (DUB-Glo(™), Promega) provides a wider dynamic range than traditional fluorogenic reagents. Unfortunately, this assay requires high enzyme concentrations and lacks specificity for DUBs over other isopeptidases (e.g. desumoylases), as it is based on an aminoluciferin (AML) derivative of a peptide derived from the C-terminus of Ub (Z-RLRGG-). Conjugation of aminoluciferin to a full-length Ub (Ub-AML) yields a substrate that has a wide dynamic range, yet displays detection limits for DUBs 100- to 1000-fold lower than observed with DUB-Glo(™). Ub-AML was even a sensitive substrate for DUBs (e.g. JosD1 and USP14) that do not show appreciable activity with DUB-Glo(™). Aminoluciferin derivatives of hSUMO2 and NEDD8 were also shown to be sensitive substrates for desumoylases and deneddylases, respectively. Ub/Ubl-AML substrates are amenable to HTS (Z′ =0.67) yielding robust signal, and providing an alternative drug discovery platform for Ub/Ubl isopeptidases.",,"['Orcutt, Steven J.', 'Wu, Jian', 'Eddins, Michael J.', 'Leach, Craig A.', 'Strickler, James E.']",,,,
,PMC,Autoproteolytic activation of ThnT results in structural reorganization necessary for substrate binding and catalysis,http://dx.doi.org/10.1016/j.jmb.2012.06.012,PMC3428426,,,"cis-Autoproteolysis is a post-translational modification necessary for the function of ThnT, an enzyme involved in the biosynthesis of the β-lactam antibiotic thienamycin. This modification generates an N-terminal threonine nucleophile that is used to hydrolyze the pantetheinyl moiety of its natural substrate. We determined the crystal structure of autoactivated ThnT to 1.8 Å through X-ray crystallography. Comparison to a mutationally inactivated precursor structure revealed several large conformational rearrangements near the active site. To probe the relevance of these transitions, we designed a pantetheine-like chloromethyl ketone (CMK) inactivator and co-crystallized it with ThnT. Although this class of inhibitor has been in use for several decades, the mode of inactivation had not been determined for an enzyme that uses an N-terminal nucleophile. The co-crystal structure revealed the CMK bound to the N-terminal nucleophile of ThnT through an ether linkage and analysis suggests inactivation through a direct displacement mechanism. More importantly, this inactivated complex shows three regions of ThnT that are critical to the formation of the substrate binding pocket undergo rearrangement upon autoproteolysis. Comparison of ThnT with other autoproteolytic enzymes of disparate evolutionary lineage revealed a high degree similarity within the pro-enzyme active site, reflecting shared chemical constraints. However, after autoproteolysis many enzymes, like ThnT, are observed to rearrange to accommodate their specific substrate. We propose this is a general phenomenon, whereby autoprocessing systems with shared chemistry may possess similar structural features that dissipate upon rearrangement into a mature state.",,"['Buller, Andrew R', 'Labonte, Jason W', 'Freeman, Michael F', 'Wright, Nathan T', 'Schildbach, Joel F', 'Townsend, Craig A']",,,,
,PMC,Antagonism of the interferon-induced OAS-RNase L pathway by murine coronavirus ns2 protein is required for virus replication and liver pathology,http://dx.doi.org/10.1016/j.chom.2012.04.011,PMC3377938,,,"Many viruses induce hepatitis in humans, highlighting the need to understand the underlying mechanisms of virus-induced liver pathology. The murine coronavirus, mouse hepatitis virus (MHV), causes acute hepatitis in its natural host and provides a useful model for understanding virus interaction with liver cells. The MHV accessory protein, ns2, antagonizes the type I interferon response and promotes hepatitis. We show that ns2 has 2’,5’-phosphodiesterase activity, which blocks the interferon inducible 2’,5’-oligoadenylate synthetase (OAS)-RNase L pathway to facilitate hepatitis development. Ns2 cleaves 2’, 5’-oligoadenylate, the product of OAS, to prevent activation of the cellular endoribonuclease RNase L and consequently block viral RNA degradation. An ns2 mutant virus was unable to replicate in the liver or induce hepatitis in wild type mice, but was highly pathogenic in RNase L deficient mice. Thus, RNase L is a critical cellular factor for protection against viral infection of the liver and the resulting hepatitis.",,"['Zhao, Ling', 'Jha, Babal K.', 'Wu, Ashley', 'Elliott, Ruth', 'Ziebuhr, John', 'Gorbalenya, Alexander E.', 'Silverman, Robert H.', 'Weiss, Susan R.']",,,,
,PMC,θ-Defensins: Cyclic Peptides with Endless Potential,http://dx.doi.org/10.1074/jbc.R112.346098,PMC3411038,,,"θ-Defensins, the only cyclic peptides of animal origin, have been isolated from the leukocytes of rhesus macaques and baboons. Their biogenesis is unusual because each peptide is an 18-residue chimera formed by the head-to-tail splicing of nonapeptides derived from two separate precursors. θ-Defensins have multiple arginines and a ladder-like tridisulfide array spanning their two antiparallel β-strands. Human θ-defensin genes contain a premature stop codon that prevents effective translation of the needed precursors; consequently, these peptides are not present in human leukocytes. Synthetic θ-defensins with sequences that correspond to those encoded within the human pseudogenes are called retrocyclins. Retrocyclin-1 inhibits the cellular entry of HIV-1, HSV, and influenza A virus. The rhesus θ-defensin RTD-1 protects mice from an experimental severe acute respiratory syndrome coronavirus infection, and retrocyclin-1 protects mice from infection by Bacillus anthracis spores. The small size, unique structure, and multiple host defense activities of θ-defensins make them intriguing potential therapeutic agents.",,"['Lehrer, Robert I.', 'Cole, Alex M.', 'Selsted, Michael E.']",,,,
,PMC,Thematic Minireview Series on Circular Proteins,http://dx.doi.org/10.1074/jbc.R112.390344,PMC3411035,,,"Circular proteins have now been discovered in all kingdoms of life and are characterized by their exceptional stability and the diversity of their biological activities, primarily in the realm of host defense functions. This thematic minireview series provides an overview of the distribution, evolution, activities, and biological synthesis of circular proteins. It also reviews approaches that biological chemists are taking to develop synthetic methods for making circular proteins in the laboratory. These approaches include solid-phase peptide synthesis based on an adaption of native chemical ligation technology and recombinant DNA approaches that are amenable to the in-cell production of cyclic peptide libraries. The thioester-mediated native chemical ligation approach mimics, to some extent, elements of the natural biosynthetic reaction, which, for disulfide-rich cyclic peptides, appears to involve asparaginyl endopeptidase-mediated processing from larger precursor proteins.",,"['Craik, David J.', 'Allewell, Norma M.']",,,,
,PMC,"Impacts of climate, land use, and biological invasion on the ecology of immature Aedes mosquitoes: Implications for La Crosse emergence",http://dx.doi.org/10.1007/s10393-012-0773-7,PMC3416954,,,"Arthropod-borne viruses (arboviruses) cause many diseases worldwide and their transmission is likely to change with land use and climate changes. La Crosse virus is historically transmitted by the native mosquito Aedes triseriatus (Say) in the upper Midwestern U.S., but the invasive congeners Aedes albopictus (Skuse) and Aedes japonicus (Theobald), which co-occur with A. triseriatus in water-holding containers, may be important accessory vectors in the Appalachian region where La Crosse encephalitis is an emerging disease. This review focuses on evidence for how climate, land use, and biological invasions may have direct abiotic and indirect community-level impacts on immature developmental stages (eggs and larvae) of Aedes mosquitoes. Because vector-borne diseases usually vary in space and time and are related to the ecology of the vector species, we propose that the ecology of its mosquito vectors, particularly at their immature stages, has played an important role in the emergence of La Crosse encephalitis in the Appalachian region and represents a model for investigating the effects of environmental changes on other vector-borne diseases. We summarize the health effects of La Crosse virus and associated socioeconomic costs that make it the most important native mosquito-borne disease in the U.S. We review of the transmission of La Crosse virus, and present evidence for the impacts of climate, land use, and biological invasions on Aedes mosquito communities. Last, we discuss important questions about the ecology of La Crosse virus mosquito vectors that may improve our understanding of the impacts of environmental changes on La Crosse virus and other arboviruses.",,"['Leisnham, Paul', 'Juliano, Steven A.']",,,,
,PMC,Ecological and anthropogenic drivers of rabies exposure in vampire bats: implications for transmission and control,http://dx.doi.org/10.1098/rspb.2012.0538,PMC3396893,,,"Despite extensive culling of common vampire bats in Latin America, lethal human rabies outbreaks transmitted by this species are increasingly recognized, and livestock rabies occurs with striking frequency. To identify the individual and population-level factors driving rabies virus (RV) transmission in vampire bats, we conducted a longitudinal capture–recapture study in 20 vampire bat colonies spanning four regions of Peru. Serology demonstrated the circulation of RV in vampire bats from all regions in all years. Seroprevalence ranged from 3 to 28 per cent and was highest in juvenile and sub-adult bats. RV exposure was independent of bat colony size, consistent with an absence of population density thresholds for viral invasion and extinction. Culling campaigns implemented during our study failed to reduce seroprevalence and were perhaps counterproductive for disease control owing to the targeted removal of adults, but potentially greater importance of juvenile and sub-adult bats for transmission. These findings provide new insights into the mechanisms of RV maintenance in vampire bats and highlight the need for ecologically informed approaches to rabies prevention in Latin America.",,"['Streicker, Daniel G.', 'Recuenco, Sergio', 'Valderrama, William', 'Gomez Benavides, Jorge', 'Vargas, Ivan', 'Pacheco, Víctor', 'Condori Condori, Rene E.', 'Montgomery, Joel', 'Rupprecht, Charles E.', 'Rohani, Pejman', 'Altizer, Sonia']",,,,
,PMC,Emerging infectious agents and the nation’s blood supply: responding to potential threats in the 21st century,http://dx.doi.org/10.1111/j.1537-2995.2012.03742.x,PMC3644861,,,,,"['Glynn, Simone A.', 'Busch, Michael P.', 'Dodd, Roger Y.', 'Katz, Louis M.', 'Stramer, Susan L.', 'Klein, Harvey G.', 'Simmons, Graham', 'Kleinman, Steven H.', 'Shurin, Susan B.']",,,,
,PMC,Infection control in the emergency department,http://dx.doi.org/10.1503/cmaj.112-2038,PMC3381768,,,,,"['Fusco, Francesco M.', 'Puro, Vincenzo']",,,,
,PMC,Incidence and implications of unrecognized viral respiratory tract infections in premature infants during their birth hospitalization: a prospective surveillance study in two neonatal intensive care units,http://dx.doi.org/10.1016/j.jpeds.2012.05.001,PMC3731035,,,"OBJECTIVE: We sought to determine the frequency and effects of nosocomial respiratory viral infections (RVIs) in premature neonates, including those who may be asymptomatic. STUDY DESIGN: We performed a year-long surveillance for RVIs in infants <33 weeks gestational age admitted to two Syracuse neonatal intensive care units (NICUs). Infants were enrolled within 3 days of NICU admission and were sampled for RVIs until discharge using a multiplex PCR assay capable of detecting 17 different respiratory viruses or subtypes. RESULTS: 26 of 50 prematurely born infants (52%) tested positive for a respiratory virus at least once during their birth hospitalization. Testing positive for a respiratory virus was significantly associated with longer length of stay (70 days vs. 35 days, p = 0.002) and prolonged ventilatory support (51 vs. 13 days, p = 0.002). Infants who tested positive for a respiratory virus during their birth hospitalization had more than twice the rate of developing bronchopulmonary dysplasia (BPD; p < 0.05). CONCLUSION: Nosocomial RVIs were frequent in our study population, despite the absence of clinical indicators of illness. Length of hospital stay was significantly longer and a diagnosis of BPD was more common in those premature infants who had respiratory viruses detected.",,"['Bennett, Nicholas J', 'Tabarani, Christy M', 'Bartholoma, Nadine M', 'Wang, Dongliang', 'Huang, Danning', 'Riddell, Scott W.', 'Kiska, Deanna L.', 'Hingre, Robert', 'Rosenberg, Helene F', 'Domachowske, Joseph B.']",,,,
,PMC,Structural Basis of Potent and Broad HIV-1 Fusion Inhibitor CP32M,http://dx.doi.org/10.1074/jbc.M112.381079,PMC3411002,,,"CP32M is a newly designed peptide fusion inhibitor possessing potent anti-HIV activity, especially against T20-resistant HIV-1 strains. In this study, we show that CP32M can efficiently inhibit a large panel of diverse HIV-1 variants, including subtype B′, CRF07_BC, and CRF01_AE recombinants and naturally occurring or induced T20-resistant viruses. To elucidate its mechanism of action, we determined the crystal structure of CP32M complexed with its target sequence. Differing from its parental peptide, CP621-652, the (621)VEWNEMT(627) motif of CP32M folds into two α-helix turns at the N terminus of the pocket-binding domain, forming a novel layer in the six-helix bundle structure. Prominently, the residue Asn-624 of the (621)VEWNEMT(627) motif is engaged in the polar interaction with a hydrophilic ridge that borders the hydrophobic pocket on the N-terminal coiled coil. The original inhibitor design of CP32M provides several intra- and salt bridge/hydrogen bond interactions favoring the stability of the helical conformation of CP32M and its interactions with N-terminal heptad repeat (NHR) targets. We identified a novel salt bridge between Arg-557 on the NHR and Glu-648 of CP32M that is critical for the binding of CP32M and resistance against the inhibitor. Therefore, our data present important information for developing novel HIV-1 fusion inhibitors for clinical use.",,"['Yao, Xue', 'Chong, Huihui', 'Zhang, Chao', 'Qiu, Zonglin', 'Qin, Bo', 'Han, Ruiyun', 'Waltersperger, Sandro', 'Wang, Meitian', 'He, Yuxian', 'Cui, Sheng']",,,,
,PMC,Drug combination therapy in control of cryptosporidiosis in Ludhiana district of Punjab,http://dx.doi.org/10.1007/s12639-012-0123-2,PMC3427675,,,The present report describes outbreak of cryptosporidiosis in neonatal cross bred cattle calves ageing 1–2 months in an organized dairy farm. The protozoan infection was confirmed by identifying bright red oocysts of Cryptosporidium spp. in the faecal samples after staining with modified acid Fast Zeihl–Neelsen stain. Metronidazole and furazolidone combination was able to induce clinically and parasitological recovery. This is believed to be the first report on the successful use of this drug combination against cryptosporidiosis.,,"['Randhawa, S. S.', 'Randhawa, Swaran S.', 'Zahid, U. N.', 'Singla, L. D.', 'Juyal, P. D.']",,,,
,PMC,The Global Dimensions of Public Health Preparedness and Implications for US Action,http://dx.doi.org/10.2105/AJPH.2011.300644,PMC3483965,,,"The globalization of public health is both real and relevant throughout the United States and to Americans traveling or residing abroad. US public policy responses are evolving, but a crisper and more comprehensive global perspective is needed. I suggest four timely US actions to address today’s competing realities of globalization and economic austerity: raise awareness among clinicians and local health departments; capture and share exemplary disaster management practices across countries; ensure that US global health investments are effective, efficient, and sustainable; and think globally while acting locally to enhance US health security. The reauthorization of the Pandemic and All-Hazards Preparedness Act of 2006 provides an opportunity to more clearly address the global dimensions of domestic preparedness.",,"Moore, Melinda",,,,
,PMC,Investigations of Selected Historically Important Syndromic Outbreaks: Impact and Lessons Learned for Public Health Preparedness and Response,http://dx.doi.org/10.2105/AJPH.2011.300426,PMC3483947,,,"Public health readiness has increased at all jurisdictional levels because of increased sensitivity to threats. Since 2001, with billions of dollars invested to bolster the public health system’s capacity, the public expects that public health will identify the etiology of and respond to events more rapidly. However, when etiologies are unknown at the onset of the investigation but interventions must be implemented, public health practitioners must benefit from past investigations’ lessons to strengthen preparedness for emerging threats. We have identified such potentially actionable lessons learned from historically important public health events that occurred primarily as syndromes for which the etiological agent initially was unknown. Ongoing analysis of investigations can advance our capability to recognize and investigate syndromes and other problems and implement the most appropriate interventions.",,"['Goodman, Richard A.', 'Posid, Joseph M.', 'Popovic, Tanja']",,,,
,PMC,Virus-Infected Alveolar Epithelial Cells Direct Neutrophil Chemotaxis and Inhibit Their Apoptosis,http://dx.doi.org/10.1165/rcmb.2011-0230OC,PMC3380290,,,"The alveolar epithelium is a critical target for pulmonary viruses and can produce proinflammatory cytokines and chemokines upon viral infection. However, the molecular interactions between virus-infected alveolar epithelial cells and inflammatory cells, including polymorphonuclear leukocytes (PMNs), have not been thoroughly characterized. Rat coronavirus (RCoV) is used as a model to study the immune response to viral infection in the lung of the natural host. We have developed an in vitro model to characterize the response of PMNs to RCoV-infected type I-like alveolar epithelial (AT1) cells, the primary target for RCoV infection in the alveoli. Multiple CXC chemokines that signal through CXCR2 were required for PMN chemotaxis toward medium from RCoV-infected AT1-like cells (RCoV-AT1). Furthermore, RCoV-AT1 inhibited spontaneous PMN apoptosis, including activation of effector caspase 3 and initiator caspases 8 and 9. Use of a selective inhibitor of CXCR2, SB265610, demonstrated that CXCR2 signaling was required for RCoV-AT1–mediated inhibition of PMN apoptosis. These data suggest that CXC chemokines produced by RCoV-infected AT1-like cells inhibit PMN apoptosis during infection. These studies provide new insight into the molecular mechanisms whereby alveolar epithelial cells direct the functions of PMNs during viral infection of the lung.",,"['Rzepka, Joanna P.', 'Haick, Anoria K.', 'Miura, Tanya A.']",,,,
,PMC,Shiga Toxin-Producing Escherichia coli O104:H4: a New Challenge for Microbiology,http://dx.doi.org/10.1128/AEM.00217-12,PMC3370534,,,"In 2011, Germany experienced the largest outbreak with a Shiga toxin-producing Escherichia coli (STEC) strain ever recorded. A series of environmental and trace-back and trace-forward investigations linked sprout consumption with the disease, but fecal-oral transmission was also documented. The genome sequences of the pathogen revealed a clonal outbreak with enteroaggregative E. coli (EAEC). Some EAEC virulence factors are carried on the virulence plasmid pAA. From an unknown source, the epidemic strains acquired a lambdoid prophage carrying the gene for the Shiga toxin. The resulting strains therefore possess two different mobile elements, a phage and a plasmid, contributing essential virulence genes. Shiga toxin is released by decaying bacteria in the gut, migrates through the intestinal barrier, and is transported via the blood to target organs, like the kidney. In a mouse model, probiotic bifidobacteria interfered with transport of the toxin through the gut mucosa. Researchers explored bacteriophages, bacteriocins, and low-molecular-weight inhibitors against STEC. Randomized controlled clinical trials of enterohemorrhagic E. coli (EHEC)-associated hemolytic uremic syndrome (HUS) patients found none of the interventions superior to supportive therapy alone. Antibodies against one subtype of Shiga toxin protected pigs against fatal neurological infection, while treatment with a toxin receptor decoy showed no effect in a clinical trial. Likewise, a monoclonal antibody directed against a complement protein led to mixed results. Plasma exchange and IgG immunoadsoprtion ameliorated the condition in small uncontrolled trials. The epidemic O104:H4 strains were resistant to all penicillins and cephalosporins but susceptible to carbapenems, which were recommended for treatment.",,"['Muniesa, Maite', 'Hammerl, Jens A.', 'Hertwig, Stefan', 'Appel, Bernd', 'Brüssow, Harald']",,,,
,PMC,Feasibility of Quantitative Environmental Surveillance in Poliovirus Eradication Strategies,http://dx.doi.org/10.1128/AEM.07972-11,PMC3346415,,,"The progress of the Global Polio Eradication Initiative is monitored by acute flaccid paralysis (AFP) surveillance supplemented with environmental surveillance in selected areas. To assess the sensitivity of environmental surveillance, stools from (re)vaccinated elderly persons with a low seroprevalence and from wastewater were concurrently collected and analyzed in the Netherlands over a prolonged period of time. A total number of 228 healthy individuals with different levels of immunity were challenged with monovalent oral polio vaccine serotype 1 or 3. Poliovirus concentrations were determined by the titration of fecal suspensions on poliovirus-sensitive L20B cells and of sewage concentrates by L20B monolayer plaque assay. Almost half of the individuals (45%) shed poliovirus on day 3 after challenge, which peaked (57%) on day 8 with an average poliovirus excretion of 1.3 × 10(5) TCID(50) per g of feces and gradually decreased to less than 5% on day 42. The virus concentrations in sewage peaked on days 6 to 8 at approximately 100 PFU per liter, remained high until day 14, and subsequently decreased to less than 10 PFU per liter on day 29. The estimated poliovirus concentration in sewage approximated the measured initial virus excretion in feces, within 1 log(10) variation, resulting in a sensitivity of detection of 100 infected but mostly asymptomatic individuals in tens of thousands of individuals. An additional second peak observed in sewage may indicate secondary transmission missed by enterovirus or AFP surveillance in patients. This enables the detection of circulating poliovirus by environmental surveillance, supporting its feasibility as an early warning system.",,"['Lodder, W. J.', 'Buisman, A. M.', 'Rutjes, S. A.', 'Heijne, J. C.', 'Teunis, P. F.', 'de Roda Husman, A. M.']",,,,
,PMC,Stability of and Attachment to Lettuce by a Culturable Porcine Sapovirus Surrogate for Human Caliciviruses,http://dx.doi.org/10.1128/AEM.06600-11,PMC3346393,,,"Human noroviruses (HuNoVs) are the leading cause of food-borne illness, accounting for 58% of U.S. cases. Because HuNoVs are unculturable, surrogates are needed to investigate transmission routes and evaluate disinfection methods. However, the current surrogates, feline calicivirus (FCV) and murine NoV (MNV), are less tolerant than HuNoVs to acid and chlorine, respectively. Porcine sapovirus (SaV) is the only culturable enteropathogenic calicivirus. In this study, the resistance of SaV to physicochemical treatments was compared to that of HuNoVs (by reverse transcription-PCR), FCV, and MNV (by infectivity assays). Sapovirus and HuNoV (viral RNA) showed similar resistances to heat (56°C) and to different concentrations of chlorine. However, SaV was more resistant than HuNoVs to ethanol treatment (60% and 70%). Like HuNoVs, SaV was stable at pH 3.0 to 8.0, with a <1.0 log(10) 50% tissue culture infective dose (TCID(50)) reduction at pH 3.0 compared to the value for pH 4.0 to 8.0. SaV and MNV showed similar resistances, and both were more resistant than FCV to heat inactivation (56°C). FCV was more resistant than MNV and SaV to ethanol, and all three viruses showed similar resistances to treatment with low concentrations of chlorine for 1 min. Those results indicate that SaV is a promising surrogate for HuNoVs. Next, we used SaV as a surrogate to examine virus attachment to lettuce at different pHs. Sapovirus attached to lettuce leaves significantly at its capsid isoelectric point (pH 5.0), and the attached viral particles remained infectious on lettuce after 1 week of storage at 4°C. The culturable SaV is a good surrogate for studying HuNoV contamination and transmission in leafy greens and potential disinfectants.",,"['Wang, Qiuhong', 'Zhang, Zhenwen', 'Saif, Linda J.']",,,,
,PMC,Serial evaluation of high-resolution CT findings in patients with pneumonia in novel swine-origin influenza A (H1N1) virus infection,http://dx.doi.org/10.1259/bjr/85580974,PMC3474108,,,"OBJECTIVES: The purpose of our study was to review the changes in the serial high-resolution CT (HRCT) findings from patients with novel swine-origin influenza A (H1N1) virus (S-OIV) infection. METHODS: HRCT findings of 70 patients with presumed or laboratory-confirmed novel S-OIV infection were reviewed. The pattern (consolidation, ground glass, fibrosis and air trapping), distribution and extent of abnormality of the lesions on the HRCT were evaluated at different time points. To assess changes that occurred over time, the CT scans in 56 patients were examined in sequence. RESULTS: The most common CT findings in patients with S-OIV infection are ground-glass opacities with or without consolidation at the first week. The abnormalities peaked at the second week and resolved after that time, which resulted in substantial reduced residual disease at 4 weeks or later. The development of fibrosis was noted in the first week and peaked at the third week of illness (34.7%), then decreased slowly after that time. The mean time of air trapping being noted after the onset of symptoms was 55.5±20.6 days. Comparing the findings of initial CT, most results (96.4%) of follow-up chest CT findings showed improvement (p<0.01). CONCLUSION: The abnormalities of ground-glass opacities and/or consolidation on initial CT scans tended to resolve to fibrosis, which then resolved completely or displayed substantially reduced residual disease. HRCT may show more changes in disease progression and play an important role in the evaluation of severe S-OIV.",,"['Li, P', 'Zhang, J-F', 'Xia, X-D', 'Su, D-J', 'Liu, B-L', 'Zhao, D-L', 'Liu, Y', 'Zhao, D-H']",,,,
,PMC,The role of torovirus in nosocomial viral gastroenteritis at a large tertiary pediatric centre,,PMC3403670,,,"OBJECTIVE: To describe the viral etiology and epidemiology of nosocomial viral gastroenteritis (NVG) at a tertiary care pediatric hospital and identify any changes over the past two decades. METHODS: Retrospective review of all patients with laboratory-confirmed NVG at The Hospital for Sick Children (Toronto, Ontario), from January 1, 2004, to December 31, 2005. RESULTS: One hundred forty-two episodes of NVG were found among 133 patients, occurring in 0.48 of 100 admissions. The median age was two years; 42% were <1 year of age and 41% were immunocompromised. The most commonly detected pathogen was torovirus (67% of episodes), followed by rotavirus (19%) and adenovirus (9%). Seventy-five cases (53%) were epidemiologically linked in 32 separate clusters (median cluster size two, range two to four). The NVG rate fell from 0.63 of 100 to 0.22 of 100 admissions after March 2005 (P<0.001) when enhanced infection control precautions were instituted in response to an outbreak of vancomycin-resistant Enterococcus. CONCLUSIONS: Torovirus remains the most commonly identified cause of NVG at The Hospital for Sick Children. Most NVG cases were epidemiologically linked, and a significant reduction in cases occurred after the institution of enhanced infection control practices following an outbreak of vancomycin-resistant Enterococcus. Improved education and surveillance for NVG should lead to further reduction in this problem.",,"['Gubbay, JB', 'Al-Rezqi, A', 'Hawkes, M', 'Williams, L', 'Richardson, SE', 'Matlow, A']",,,,
,PMC,Is There a Starling Curve for Intensive Care?,http://dx.doi.org/10.1378/chest.11-2819,PMC3367487,,,"Large differences exist in the provision of ICU beds worldwide, with a complicated mix of risks and benefits to the population of having either too few or too many beds. Having too few beds can result in delayed admission of patients to the ICU or no admission at all, with either scenario potentially increasing mortality. Potential societal benefits of having few beds include lower costs for health care and less futile intensive care at the end of life. With added ICU beds for a population, mortality benefit should accrue, but there is still the question of whether the addition of beds always means that more lives will be saved or whether there is a point at which no additional mortality benefit is gained. With an abundance of ICU beds may come the possibility of increasing harm in the forms of unnecessary costs, poor quality of deaths (ie, excessively intensive), and iatrogenic complications. The possibility of harm may be likened to the concept of falling off a Starling curve, which is traditionally used to describe worsening heart function when overfilling occurs. This commentary examines the possible implications of having too few or too many ICU beds and proposes the concept of a family of Starling curves as a way to conceptualize the balance of societal benefits and harms associated with different availability of ICU beds for a population.",,"Wunsch, Hannah",,,,
,PMC,Large-scale sequencing and the natural history of model human RNA viruses,http://dx.doi.org/10.2217/fvl.12.45,PMC3653332,,,"RNA virus exploration within the field of medical virology has greatly benefited from technological developments in genomics, deepening our understanding of viral dynamics and emergence. Large-scale first-generation technology sequencing projects have expedited molecular epidemiology studies at an unprecedented scale for two pathogenic RNA viruses chosen as models: influenza A virus and dengue. Next-generation sequencing approaches are now leading to a more in-depth analysis of virus genetic diversity, which is greater for RNA than DNA viruses because of high replication rates and the absence of proofreading activity of the RNA-dependent RNA polymerase. In the field of virus discovery, technological advancements and metagenomic approaches are expanding the catalogs of novel viruses by facilitating our probing into the RNA virus world.",,"['Dugan, Vivien G', 'Saira, Kazima', 'Ghedin, Elodie']",,,,
,PMC,Regulatory T cells and Th17 cells in viral infections: implications for multiple sclerosis and myocarditis,http://dx.doi.org/10.2217/fvl.12.44,PMC3457923,,,"In immune-mediated diseases, Treg and proinflammatory Th17 cells have been suggested to play either suppressor (beneficial) or effector (detrimental) roles, respectively. Tissue damage in viral infections can be caused by direct viral replication or immunopathology. Viral replication can be enhanced by anti-inflammatory responses and suppressed by proinflammatory responses. However, Tregs could suppress proinflammatory responses, reducing immunopathology, while Th17 cell-induced inflammation may enhance immunopathology. Here, the roles of Treg and Th17 cells depend on whether tissue damage is caused by direct virus replication or immunopathology, which differ depending on the virus, disease stage and host immune background. Although the precise mechanisms of tissue damage in multiple sclerosis and myocarditis are unclear, both viral replication and immune effector cells have been proposed to cause pathogenesis. Personalized medicine that alters the balance between Treg and Th17 cells may ameliorate viral pathology during infections.",,"['Martinez, Nicholas E', 'Sato, Fumitaka', 'Kawai, Eiichiro', 'Omura, Seiichi', 'Chervenak, Robert P', 'Tsunoda, Ikuo']",,,,
,PMC,Association of translation factor eEF1A with defective ribosomal products generates a signal for aggresome formation,http://dx.doi.org/10.1242/jcs.098954,PMC3403235,,,"Aggresome formation is initiated upon proteasome failure, and facilitates autophagic clearance of protein aggregates to protect cells from proteotoxicity. Here we demonstrate that proteasome inhibition generates a signaling event to trigger aggresome formation. In aggresome signaling, the cell senses a build-up of aberrant newly synthesized proteins. The translation elongation factor eEF1A associated with these species, and knockdown of this factor suppressed aggresome formation. We used the Legionella toxin SidI to distinguish between the function of eEF1A in translation and its novel function in the aggresome formation. In fact, although it strongly inhibited translation, this toxin had only a marginal effect on aggresome formation. Furthermore, SidI reduced the threshold of the aberrant ribosomal products for triggering aggresome formation. Therefore, eEF1A binds defective polypeptides released from ribosomes, which generates a signal that triggers aggresome formation.",,"['Meriin, Anatoli B.', 'Zaarur, Nava', 'Sherman, Michael Y.']",,,,
,PMC,"Two Adenovirus Serotype 3 Outbreaks Associated with Febrile Respiratory Disease and Pharyngoconjunctival Fever in Children under 15 Years of Age in Hangzhou, China, during 2011",http://dx.doi.org/10.1128/JCM.06523-11,PMC3372113,,,"Adenovirus serotype 3 and 7 outbreaks have occurred periodically in northern, eastern, and southern China since 1955, but there has been no report since the adenovirus serotype 7 outbreak first occurred in Hangzhou, China, in 1991. Here we explored the epidemiology and etiology of two adenovirus serotype 3 outbreaks in Hangzhou in 2011. One acute respiratory outbreak was found in Chun'an County, where a total of 371 cases were confirmed in 5 of 23 towns from 4 to 31 May 2011. The outbreak affected 18.57% (13/70) of schools and 14.49% (90/621) of classes. The incidence was 5.18% (371/7,163). The population was distributed among individuals ages 7 to 15 years. No parents or teachers were infected. Another pharyngoconjunctival fever outbreak was discovered in the Chenjinglun Swimming Center located in the Xihu District between 1 and 15 July 2011. A total of 134 cases were confirmed in 900 amateur swimmers, with an incidence of 14.89% (134/900). The ages ranged from 4 to 9 years. The two outbreaks had no severe complications or death. The viruses in 66.67% (10/15) of throat swabs from children with acute respiratory infections and 100% (10/10) of the swabs from children with pharyngoconjunctival fever were confirmed to be adenovirus serotype 3 with 100% homology by PCR. Of these samples, 60.0% (12/20) had a classical characteristic cytopathic effect, presented as grape-like clusters at 72 h after infection in HEp-2 cells. In conclusion, the acute respiratory infection and pharyngoconjunctival fever outbreak in Hangzhou were caused by the completely homologous type 3 adenovirus in subgenus B. Moreover, these outbreaks demonstrated rapid transmission rates, possibly due to close contact and droplet transmission.",,"['Xie, Li', 'Yu, Xin-Fen', 'Sun, Zhou', 'Yang, Xu-Hui', 'Huang, Ren-Jie', 'Wang, Jing', 'Yu, Apeng', 'Zheng, Lin', 'Yu, Man-Chu', 'Hu, Xiao-Wei', 'Wang, Ban-Ma', 'Chen, Jin', 'Pan, Jing-Cao', 'Liu, She-Lan']",,,,
,PMC,CD40-targeted adenoviral cancer vaccines: the long and winding road to the clinic,http://dx.doi.org/10.1002/jgm.1648,PMC3433169,,,"The ability of Dendritic Cells (DC) to orchestrate innate and adaptive immune responses has been exploited to develop potent anti-cancer immunotherapies. Recent clinical trials exploring the efficacy of ex vivo modified autologous DC-based vaccines have reported some promising results. However, in vitro generation of autologous DC for clinical administration, their loading with tumor associated antigens (TAA) and their activation, is laborious and expensive, and, due to interindividual variability in the personalized vaccines, poorly standardized. An attractive alternative approach is to load resident DC in vivo by targeted delivery of TAA , using viral vectors and activating them simultaneously. To this end we have constructed genetically modified Adenoviral (Ad) vectors and bispecific adaptor molecules to retarget Ad vectors encoding TAA to the CD40 receptor on DC. Preclinical human and murine studies conducted so far have clearly demonstrated the suitability of a “two-component”, i.e. Ad and adaptor molecule, configuration for targeted modification of DC in vivo for cancer immunotherapy. This review summarizes recent progress in the development of CD40-targeted Ad-based cancer vaccines and highlights pre-clinical issues in clinical translation of this approach.",,"['Hangalapura, Basav N.', 'Timares, Laura', 'Oosterhoff, Dinja', 'Scheper, Rik J.', 'Curiel, David T.', 'de Gruijl, Tanja D.']",,,,
,PMC,Collaboration and Team Science: From Theory to Practice,http://dx.doi.org/10.231/JIM.0b013e318250871d,PMC3652225,,,"Interdisciplinary efforts are becoming more critical for scientific discovery and translational research efforts. Highly integrated and interactive research teams share a number of features that contribute to their success in developing and sustaining their efforts over time. Through analysis of in-depth interviews with members of highly successful research teams and others that did not meet their goals or ended due to conflicts, we identified key elements that appear critical for team success and effectiveness. There is no debate that the scientific goal sits at the center of the collaborative effort. However, supporting features need to be in place to avoid the derailment of the team. Among the most important of these is trust: without trust the team dynamic runs the risk of deteriorating over time. Other critical factors of which both leaders and participants need to be aware include developing a shared vision, strategically identifying team members and purposefully building the team, promoting disagreement while containing conflict, and setting clear expectations for sharing credit and authorship. Self-awareness and strong communication skills contribute greatly to effective leadership and management strategies of scientific teams. While all successful teams share the characteristic of effectively carrying out these activities, there is no single formula for execution with every leader exemplifying different strengths and weaknesses. Successful scientific collaborations have strong leaders who are self -aware and are mindful of the many elements critical for supporting the science at the center of the effort.",,"['Bennett, L. Michelle', 'Gadlin, Howard']",,,,
,PMC,A Reverse Genetics Approach To Study Feline Infectious Peritonitis,http://dx.doi.org/10.1128/JVI.00023-12,PMC3393577,,,"Feline infectious peritonitis (FIP) is a lethal immunopathological disease caused by feline coronaviruses (FCoVs). Here, we describe a reverse genetics approach to study FIP by assessing the pathogenicity of recombinant type I and type II and chimeric type I/type II FCoVs. All recombinant FCoVs established productive infection in cats, and recombinant type II FCoV (strain 79-1146) induced FIP. Virus sequence analyses from FIP-diseased cats revealed that the 3c gene stop codon of strain 79-1146 has changed to restore a full-length open reading frame (ORF).",,"['Tekes, Gergely', 'Spies, Danica', 'Bank-Wolf, Barbara', 'Thiel, Volker', 'Thiel, Heinz-Jürgen']",,,,
,PMC,Oct4(+) Stem/Progenitor Swine Lung Epithelial Cells Are Targets for Influenza Virus Replication,http://dx.doi.org/10.1128/JVI.00341-12,PMC3393566,,,"We isolated stem/progenitor epithelial cells from the lungs of 4- to 6-week-old pigs. The epithelial progenitor colony cells were surrounded by mesenchymal stromal cells. The progenitor epithelial colony cells expressed stem cell markers such as octamer binding transcription factor 4 (Oct4) and stage-specific embryonic antigen 1 (SSEA-1), as well as the epithelial markers pancytokeratin, cytokeratin-18, and occludin, but not mesenchymal (CD44, CD29, and CD90) and hematopoietic (CD45) markers. The colony cells had extensive self-renewal potential and had the capacity to undergo differentiation to alveolar type I- and type II-like pneumocytes. Additionally, these cells expressed sialic acid receptors and supported the active replication of influenza virus, which was accompanied by cell lysis. The lysis of progenitor epithelial cells by influenza virus may cause a marked reduction in the potential of progenitor cells for self renewal and for their ability to differentiate into specialized cells of the lung. These observations suggest the possible involvement of lung stem/progenitor cells in influenza virus infection.",,"['Khatri, Mahesh', 'Goyal, Sagar M.', 'Saif, Yehia M.']",,,,
,PMC,Complete Genome Sequence of a Novel Porcine Enterovirus Strain in China,http://dx.doi.org/10.1128/JVI.00711-12,PMC3393563,,,"The porcine enteroviruses (PEVs) belong to the family Picornaviridae. We report a complete genome sequence of a novel PEV strain that is widely prevalent in pigs at least in central and eastern China. The complete genome consists of 7,390 nucleotides, excluding the 3′ poly(A) tail, and has an open reading frame that maps between nucleotide positions 812 and 7318 and encodes a 2,168-amino-acid polyprotein. Phylogenetic analysis based on the 3CD and VP1 regions reveals that this PEV strain belongs to a species of PEV9 but may represent a novel sero-/genotype in CPE group III. We also report the major findings from bootscan analysis based on the whole genomes of PEVs in the present study and those available in GenBank.",,"['Zhang, Wen', 'Yang, Shixing', 'Shen, Quan', 'Ren, Liping', 'Shan, Tongling', 'Wei, Jianzhong', 'Cui, Li', 'Hua, Xiuguo']",,,,
,PMC,Feline Tetherin Is Characterized by a Short N-Terminal Region and Is Counteracted by the Feline Immunodeficiency Virus Envelope Glycoprotein,http://dx.doi.org/10.1128/JVI.07037-11,PMC3393548,,,"Tetherin (BST2) is the host cell factor that blocks the particle release of some enveloped viruses. Two putative feline tetherin proteins differing at the level of the N-terminal coding region have recently been described and tested for their antiviral activity. By cloning and comparing the two reported feline tetherins (called here cBST2(504) and cBST2*) and generating specific derivative mutants, this study provides evidence that feline tetherin has a shorter intracytoplasmic domain than those of other known homologues. The minimal tetherin promoter was identified and assayed for its ability to drive tetherin expression in an alpha interferon-inducible manner. We also demonstrated that cBST2(504) is able to dimerize, is localized at the cellular membrane, and impairs human immunodeficiency virus type 1 (HIV-1) particle release, regardless of the presence of the Vpu antagonist accessory protein. While cBST2(504) failed to restrict wild-type feline immunodeficiency virus (FIV) egress, FIV mutants, bearing a frameshift at the level of the envelope-encoding region, were potently blocked. The transient expression of the FIV envelope glycoprotein was able to rescue mutant particle release from feline tetherin-positive cells but did not antagonize human BST2 activity. Moreover, cBST2(504) was capable of specifically immunoprecipitating the FIV envelope glycoprotein. Finally, cBST2(504) also exerted its function on HIV-2 ROD10 and on the simian immunodeficiency virus SIVmac239. Taken together, these results show that feline tetherin does indeed have a short N-terminal region and that the FIV envelope glycoprotein is the predominant factor counteracting tetherin restriction.",,"['Celestino, Michele', 'Calistri, Arianna', 'Del Vecchio, Claudia', 'Salata, Cristiano', 'Chiuppesi, Flavia', 'Pistello, Mauro', 'Borsetti, Alessandra', 'Palù, Giorgio', 'Parolin, Cristina']",,,,
,PMC,Mice Deficient in STAT1 but Not STAT2 or IRF9 Develop a Lethal CD4(+) T-Cell-Mediated Disease following Infection with Lymphocytic Choriomeningitis Virus,http://dx.doi.org/10.1128/JVI.07147-11,PMC3393544,,,"Interferon (IFN) signaling is crucial for antiviral immunity. While type I IFN signaling is mediated by STAT1, STAT2, and IRF9, type II IFN signaling requires only STAT1. Here, we studied the roles of these signaling factors in the host response to systemic infection with lymphocytic choriomeningitis virus (LCMV). In wild-type (WT) mice and mice lacking either STAT2 or IRF9, LCMV infection was nonlethal, and the virus either was cleared (WT) or established persistence (STAT2 knockout [KO] and IRF9 KO). However, in the case of STAT1 KO mice, LCMV infection was lethal and accompanied by severe multiorgan immune pathology, elevated expression of various cytokine genes in tissues, and cytokines in the serum. This lethal phenotype was unaltered by the coabsence of the gamma interferon (IFN-γ) receptor and hence was not dependent on IFN-γ. Equally, the disease was not due to a combined defect in type I and type II IFN signaling, as IRF9 KO mice lacking the IFN-γ receptor survived infection with LCMV. Clearance of LCMV is mediated normally by CD8(+) T cells. However, the depletion of these cells in LCMV-infected STAT1 KO mice was delayed, but did not prevent, lethality. In contrast, depletion of CD4(+) T cells prevented lethality in LCMV-infected STAT1 KO mice and was associated with a reduction in tissue immune pathology. These studies highlight a fundamental difference in the role of STAT1 versus STAT2 and IRF9. While all three factors are required to limit viral replication and spread, only STAT1 has the unique function of preventing the emergence of a lethal antiviral CD4(+) T-cell response.",,"['Hofer, Markus J.', 'Li, Wen', 'Manders, Peter', 'Terry, Rachael', 'Lim, Sue Ling', 'King, Nicholas J. C.', 'Campbell, Iain L.']",,,,
,PMC,A Triclade DNA Vaccine Designed on the Basis of a Comprehensive Serologic Study Elicits Neutralizing Antibody Responses against All Clades and Subclades of Highly Pathogenic Avian Influenza H5N1 Viruses,http://dx.doi.org/10.1128/JVI.06930-11,PMC3393539,,,"Because of their rapid evolution, genetic diversity, broad host range, ongoing circulation in birds, and potential human-to-human transmission, H5N1 influenza viruses remain a major global health concern. Their high degree of genetic diversity also poses enormous burdens and uncertainties in developing effective vaccines. To overcome this, we took a new approach, i.e., the development of immunogens based on a comprehensive serologic study. We constructed DNA plasmids encoding codon-optimized hemagglutinin (HA) from 17 representative strains covering all reported clades and subclades of highly pathogenic avian influenza H5N1 viruses. Using DNA plasmids, we generated the corresponding H5N1 pseudotypes and immune sera. We performed an across-the-board pseudotype-based neutralization assay and determined antigenic clusters by cartography. We then designed a triclade DNA vaccine and evaluated its immunogenicity and protection in mice. We report here that (sub)clades 0, 1, 3, 4, 5, 6, 7.1, and 9 were grouped into antigenic cluster 1, (sub)clades 2.1.3.2, 2.3.4, 2.4, 2.5, and 8 were grouped into another antigenic cluster, with subclade 2.2.1 loosely connected to it, and each of subclades 2.3.2.1 and 7.2 was by itself. Importantly, the triclade DNA vaccine encoding HAs of (sub)clades 0, 2.3.2.1, and 7.2 elicited broadly neutralizing antibody responses against all H5 clades and subclades and protected mice against high-lethal-dose heterologous H5N1 challenge. Thus, we conclude that broadly neutralizing antibodies against all H5 clades and subclades can indeed be elicited with immunogens on the basis of a comprehensive serologic study. Further evaluation and optimization of such an approach in ferrets and in humans is warranted.",,"['Zhou, Fan', 'Wang, Guiqin', 'Buchy, Philippe', 'Cai, Zhipeng', 'Chen, Honglin', 'Chen, Zhiwei', 'Cheng, Genhong', 'Wan, Xiu-Feng', 'Deubel, Vincent', 'Zhou, Paul']",,,,
,PMC,Simultaneous Treatment of Human Bronchial Epithelial Cells with Serine and Cysteine Protease Inhibitors Prevents Severe Acute Respiratory Syndrome Coronavirus Entry,http://dx.doi.org/10.1128/JVI.00094-12,PMC3393535,,,"The type II transmembrane protease TMPRSS2 activates the spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) on the cell surface following receptor binding during viral entry into cells. In the absence of TMPRSS2, SARS-CoV achieves cell entry via an endosomal pathway in which cathepsin L may play an important role, i.e., the activation of spike protein fusogenicity. This study shows that a commercial serine protease inhibitor (camostat) partially blocked infection by SARS-CoV and human coronavirus NL63 (HCoV-NL63) in HeLa cells expressing the receptor angiotensin-converting enzyme 2 (ACE2) and TMPRSS2. Simultaneous treatment of the cells with camostat and EST [(23,25)trans-epoxysuccinyl-l-leucylamindo-3-methylbutane ethyl ester], a cathepsin inhibitor, efficiently prevented both cell entry and the multistep growth of SARS-CoV in human Calu-3 airway epithelial cells. This efficient inhibition could be attributed to the dual blockade of entry from the cell surface and through the endosomal pathway. These observations suggest camostat as a candidate antiviral drug to prevent or depress TMPRSS2-dependent infection by SARS-CoV.",,"['Kawase, Miyuki', 'Shirato, Kazuya', 'van der Hoek, Lia', 'Taguchi, Fumihiro', 'Matsuyama, Shutoku']",,,,
,PMC,"Integrated Clinical, Pathologic, Virologic, and Transcriptomic Analysis of H5N1 Influenza Virus-Induced Viral Pneumonia in the Rhesus Macaque",http://dx.doi.org/10.1128/JVI.00365-12,PMC3372212,,,"Viral pneumonia has been frequently reported during early stages of influenza virus pandemics and in many human cases of highly pathogenic avian influenza (HPAI) H5N1 virus infection. To better understand the pathogenesis of this disease, we produced nonlethal viral pneumonia in rhesus macaques by using an HPAI H5N1 virus (A/Anhui/2/2005; referred to as Anhui/2). Infected macaques were monitored for 14 days, and tissue samples were collected at 6 time points for virologic, histopathologic, and transcriptomic analyses. Anhui/2 efficiently replicated in the lung from 12 h to 3 days postinfection (p.i.) and caused temporal but severe pneumonia that began to resolve by day 14. Lung transcriptional changes were first observed at 6 h, and increased expression of vascular permeability regulators and neutrophil chemoattractants correlated with increased serum leakage and neutrophil infiltration in situ. Additional inflammatory, antiviral, and apoptotic genes were upregulated from 12 h, concurrent with viral antigen detection and increasing immune cell populations. A shift toward upregulation of acquired immunity was apparent after day 6. Expression levels of established immune cell molecular markers revealed remarkable similarity with pathological findings, indicating early and robust neutrophil infiltration, a slight delay in macrophage accumulation, and abundant late populations of T lymphocytes. We also characterized the putative mechanisms regulating a unique, pneumonia-associated biphasic fever pattern. Thus, this study is the first to use a comprehensive and integrative approach to delineate specific molecular mechanisms regulating influenza virus-induced pneumonia in nonhuman primates, an important first step toward better management of human influenza virus disease.",,"['Shinya, Kyoko', 'Gao, Yuwei', 'Cilloniz, Cristian', 'Suzuki, Yasuhiro', 'Fujie, Masahiro', 'Deng, Guohua', 'Zhu, Qiyun', 'Fan, Shufang', 'Makino, Akiko', 'Muramoto, Yukiko', 'Fukuyama, Satoshi', 'Tamura, Daisuke', 'Noda, Takeshi', 'Eisfeld, Amie J.', 'Katze, Michael G.', 'Chen, Hualan', 'Kawaoka, Yoshihiro']",,,,
,PMC,Molecular Characterization of Feline Infectious Peritonitis Virus Strain DF-2 and Studies of the Role of ORF3abc in Viral Cell Tropism,http://dx.doi.org/10.1128/JVI.00189-12,PMC3372193,,,"The full-length genome of the highly lethal feline infectious peritonitis virus (FIPV) strain DF-2 was sequenced and cloned into a bacterial artificial chromosome (BAC) to study the role of ORF3abc in the FIPV-feline enteric coronavirus (FECV) transition. The reverse genetic system allowed the replacement of the truncated ORF3abc of the original FIPV DF-2 genome with the intact ORF3abc of the canine coronavirus (CCoV) reference strain Elmo/02. The in vitro replication kinetics of these two viruses was studied in CrFK and FCWF-4 cell lines, as well as in feline peripheral blood monocytes. Both viruses showed similar replication kinetics in established cell lines. However, the strain with a full-length ORF3 showed markedly lower replication of more than 2 log(10) titers in feline peripheral blood monocytes. Our results suggest that the truncated ORF3abc plays an important role in the efficient macrophage/monocyte tropism of type II FIPV.",,"['Bálint, Ádám', 'Farsang, Attila', 'Zádori, Zoltán', 'Hornyák, Ákos', 'Dencső, László', 'Almazán, Fernando', 'Enjuanes, Luis', 'Belák, Sándor']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00875-12,PMC3372185,,,,,,,,,
,PMC,Evidence for ACE2-Utilizing Coronaviruses (CoVs) Related to Severe Acute Respiratory Syndrome CoV in Bats,http://dx.doi.org/10.1128/JVI.00311-12,PMC3372174,,,"In 2002, severe acute respiratory syndrome (SARS)-coronavirus (CoV) appeared as a novel human virus with high similarity to bat coronaviruses. However, while SARS-CoV uses the human angiotensin-converting enzyme 2 (ACE2) receptor for cellular entry, no coronavirus isolated from bats appears to use ACE2. Here we show that signatures of recurrent positive selection in the bat ACE2 gene map almost perfectly to known SARS-CoV interaction surfaces. Our data indicate that ACE2 utilization preceded the emergence of SARS-CoV-like viruses from bats.",,"['Demogines, Ann', 'Farzan, Michael', 'Sawyer, Sara L.']",,,,
,PMC,Effectiveness of Patient-Collected Swabs for Influenza Testing,http://dx.doi.org/10.1016/j.mayocp.2012.02.011,PMC3538476,,,"OBJECTIVE: To compare the effectiveness of self-collected and health care worker (HCW)–collected nasal swabs for detection of influenza viruses and determine the patients' preference for type of collection. PATIENTS AND METHODS: We enrolled adult patients presenting with influenzalike illness to the Emergency Department at Mayo Clinic, Rochester, Minnesota, from January 28, 2011, through April 30, 2011. Patients self-collected a midturbinate nasal flocked swab from their right nostril following written instructions. A second swab was then collected by an HCW from the left nostril. Swabs were tested for influenza A and B viruses by real-time reverse transcription–polymerase chain reaction, and percent concordance between collection methods was determined. RESULTS: Of the 72 paired specimens analyzed, 25 were positive for influenza A or B RNA by at least one of the collection methods (34.7% positivity rate). When the 14 patients who had prior health care training were excluded, the qualitative agreement between collection methods was 94.8% (55 of 58). Two of the 58 specimens (3.4%) from patients without health care training were positive only by HCW collection, and 1 of 58 (1.7%) was positive only by patient self-collection. A total of 53.4% of patients (31 of 58) preferred the self-collection method over the HCW collection, and 25.9% (15 of 58) had no preference. CONCLUSION: Self-collected midturbinate nasal swabs provide a reliable alternative to HCW collection for influenza A and B virus real-time reverse transcription–polymerase chain reaction.",,"['Dhiman, Neelam', 'Miller, Rita M.', 'Finley, Janet L.', 'Sztajnkrycer, Matthew D.', 'Nestler, David M.', 'Boggust, Andy J.', 'Jenkins, Sarah M.', 'Smith, Thomas F.', 'Wilson, John W.', 'Cockerill, Franklin R.', 'Pritt, Bobbi S.']",,,,
,PMC,Diversity in Genetic In Vivo Methods for Protein-Protein Interaction Studies: from the Yeast Two-Hybrid System to the Mammalian Split-Luciferase System,http://dx.doi.org/10.1128/MMBR.05021-11,PMC3372256,,,"Summary: The yeast two-hybrid system pioneered the field of in vivo protein-protein interaction methods and undisputedly gave rise to a palette of ingenious techniques that are constantly pushing further the limits of the original method. Sensitivity and selectivity have improved because of various technical tricks and experimental designs. Here we present an exhaustive overview of the genetic approaches available to study in vivo binary protein interactions, based on two-hybrid and protein fragment complementation assays. These methods have been engineered and employed successfully in microorganisms such as Saccharomyces cerevisiae and Escherichia coli, but also in higher eukaryotes. From single binary pairwise interactions to whole-genome interactome mapping, the self-reassembly concept has been employed widely. Innovative studies report the use of proteins such as ubiquitin, dihydrofolate reductase, and adenylate cyclase as reconstituted reporters. Protein fragment complementation assays have extended the possibilities in protein-protein interaction studies, with technologies that enable spatial and temporal analyses of protein complexes. In addition, one-hybrid and three-hybrid systems have broadened the types of interactions that can be studied and the findings that can be obtained. Applications of these technologies are discussed, together with the advantages and limitations of the available assays.",,"['Stynen, Bram', 'Tournu, Hélène', 'Tavernier, Jan', 'Van Dijck, Patrick']",,,,
,PMC,Viral Quasispecies Evolution,http://dx.doi.org/10.1128/MMBR.05023-11,PMC3372249,,,"Summary: Evolution of RNA viruses occurs through disequilibria of collections of closely related mutant spectra or mutant clouds termed viral quasispecies. Here we review the origin of the quasispecies concept and some biological implications of quasispecies dynamics. Two main aspects are addressed: (i) mutant clouds as reservoirs of phenotypic variants for virus adaptability and (ii) the internal interactions that are established within mutant spectra that render a virus ensemble the unit of selection. The understanding of viruses as quasispecies has led to new antiviral designs, such as lethal mutagenesis, whose aim is to drive viruses toward low fitness values with limited chances of fitness recovery. The impact of quasispecies for three salient human pathogens, human immunodeficiency virus and the hepatitis B and C viruses, is reviewed, with emphasis on antiviral treatment strategies. Finally, extensions of quasispecies to nonviral systems are briefly mentioned to emphasize the broad applicability of quasispecies theory.",,"['Domingo, Esteban', 'Sheldon, Julie', 'Perales, Celia']",,,,
,PMC,Doctors – paradoxes and possibilities,http://dx.doi.org/10.4066/AMJ.2012.1225,PMC3395282,,,,,"Jiwa, Moyez",,,,
,PMC,Inborn errors of human STAT1: allelic heterogeneity governs the diversity of immunological and infectious phenotypes,http://dx.doi.org/10.1016/j.coi.2012.04.011,PMC3477860,,,"The genetic dissection of various human infectious diseases has led to the definition of inborn errors of human STAT1 immunity of four types, including (i) autosomal recessive (AR) complete STAT1 deficiency, (ii) AR partial STAT1 deficiency, (iii) autosomal dominant (AD) STAT1 deficiency, and (iv) AD gain of STAT1 activity. The two types of AR STAT1 defect give rise to a broad infectious phenotype with susceptibility to intramacrophagic bacteria (mostly mycobacteria) and viruses (herpes viruses at least), due principally to the impairment of IFN-γ-mediated and IFN-α/β-mediated immunity, respectively. Clinical outcome depends on the extent to which the STAT1 defect decreases responsiveness to these cytokines. AD STAT1 deficiency selectively predisposes individuals to mycobacterial disease, owing to the impairment of IFN-γ-mediated immunity, as IFN-α/β-mediated immunity is maintained. Finally, AD gain of STAT1 activity is associated with autoimmunity, probably owing to an enhancement of IFN-α/β-mediated immunity. More surprisingly, it is also associated with chronic mucocutaneous candidiasis, through as yet undetermined mechanisms involving an inhibition of the development of IL-17-producing T cells. Thus, germline mutations in human STAT1 define four distinct clinical disorders. Various combinations of viral, mycobacterial and fungal infections are therefore allelic at the human STAT1 locus. These experiments of Nature neatly highlight the clinical and immunological impact of the human genetic dissection of infectious phenotypes.",,"['Boisson-Dupuis, Stephanie', 'Kong, Xiao-Fei', 'Okada, Satoshi', 'Cypowyj, Sophie', 'Puel, Anne', 'Abel, Laurent', 'Casanova, Jean-Laurent']",,,,
,PMC,CD147 and AGR2 expression promote cellular proliferation and metastasis of Head and Neck Squamous Cell Carcinoma,http://dx.doi.org/10.1016/j.yexcr.2012.04.022,PMC3951318,,,"The signaling pathways facilitating metastasis of head and neck squamous cell carcinoma (HNSCC) cells are not fully understood. CD147 is a transmembrane glycoprotein known to induce cell migration and invasion. AGR2 is a secreted peptide also known to promote cell metastasis. Here we describe their importance in the migration and invasion of HNSCC cells (FADU and OSC-19) in vitro and in vivo. In vitro, knockdown of CD147 or AGR2 decreased cellular proliferation, migration and invasion. In vivo, knockdown of CD147 or AGR2 expression decreased primary tumor growth as well as regional and distant metastasis.",,"['Sweeny, Larissa', 'Liu, Zhiyong', 'Bush, Benjamin D.', 'Hartman, Yolanda', 'Zhou, Tong', 'Rosenthal, Eben L.']",,,,
,PMC,Identification of New Autoantigens for Primary Biliary Cirrhosis Using Human Proteome Microarrays,http://dx.doi.org/10.1074/mcp.M111.015529,PMC3434773,,,"Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown etiology and is considered to be an autoimmune disease. Autoantibodies are important tools for accurate diagnosis of PBC. Here, we employed serum profiling analysis using a human proteome microarray composed of about 17,000 full-length unique proteins and identified 23 proteins that correlated with PBC. To validate these results, we fabricated a PBC-focused microarray with 21 of these newly identified candidates and nine additional known PBC antigens. By screening the PBC microarrays with additional cohorts of 191 PBC patients and 321 controls (43 autoimmune hepatitis, 55 hepatitis B virus, 31 hepatitis C virus, 48 rheumatoid arthritis, 45 systematic lupus erythematosus, 49 systemic sclerosis, and 50 healthy), six proteins were confirmed as novel PBC autoantigens with high sensitivities and specificities, including hexokinase-1 (isoforms I and II), Kelch-like protein 7, Kelch-like protein 12, zinc finger and BTB domain-containing protein 2, and eukaryotic translation initiation factor 2C, subunit 1. To facilitate clinical diagnosis, we developed ELISA for Kelch-like protein 12 and zinc finger and BTB domain-containing protein 2 and tested large cohorts (297 PBC and 637 control sera) to confirm the sensitivities and specificities observed in the microarray-based assays. In conclusion, our research showed that a strategy using high content protein microarray combined with a smaller but more focused protein microarray can effectively identify and validate novel PBC-specific autoantigens and has the capacity to be translated to clinical diagnosis by means of an ELISA-based method.",,"['Hu, Chao-Jun', 'Song, Guang', 'Huang, Wei', 'Liu, Guo-Zhen', 'Deng, Chui-Wen', 'Zeng, Hai-Pan', 'Wang, Li', 'Zhang, Feng-Chun', 'Zhang, Xuan', 'Jeong, Jun Seop', 'Blackshaw, Seth', 'Jiang, Li-Zhi', 'Zhu, Heng', 'Wu, Lin', 'Li, Yong-Zhe']",,,,
,PMC,Specific elevation of DcR3 in sera of sepsis patients and its potential role as a clinically important biomarker of sepsis,http://dx.doi.org/10.1016/j.diagmicrobio.2012.04.008,PMC3396789,,,"Because of its potentially important role in the pathogenesis of sepsis, the expression of soluble decoy receptor 3 (DcR3) was investigated in sera of sepsis patients. The serum levels of DcR3 and its TNF-like ligand TL1A and homologous decoy receptor OPG were quantified by ELISA. The values of DcR3 to diagnose sepsis were analyzed by receiver-operating characteristic (ROC) curves. The results showed that DcR3 was significantly elevated in sepsis compared to SIRS (systemic inflammatory response syndrome), a condition similar to sepsis but resulting from noninfectious insults. DcR3 showed superior area under the ROC curve (AUC, 0.958) compared to poor AUCs of TL1A and OPG. At a cut-off of 3.24 ng/ml, DcR3 predicted sepsis from SIRS with 96% sensitivity and 82.6% specificity. DcR3 also predicted sepsis from cancer and inflammatory bowel disease with equally excellent values. Therefore, DcR3 serum level has the potential to serve as a reliable biomarker of sepsis.",,"['Kim, Sunghee', 'Mi, Lijun', 'Zhang, Lurong']",,,,
,PMC,Biomimetic monolayer-protected gold nanoparticles for immunorecognition,http://dx.doi.org/10.1039/c2nr30467h,PMC3376232,,,"Gold nanoparticles (AuNPs) protected by self-assembled monolayers (SAMs) are capable of presenting precisely engineered surfaces at the nanoscale, allowing the mimicry of biomacromolecules on an artificial platform. Here we review the generation, characterization, and applications of monolayer-protected AuNPs that have been designed for immunorecognition by the integration of an oligopeptide epitope into the protecting monolayer. The resulting peptide-AuNP conjugate is an effective platform for biomimesis, as demonstrated by multiple studies. Recent work is presented and future directions for this field of research are discussed.",,"['Harkness, Kellen M.', 'Turner, Brian N.', 'Agrawal, Amanda C.', 'Zhang, Yibin', 'McLean, John A.', 'Cliffel, David E.']",,,,
,PMC,RNA 3'-end mismatch excision by the severe acute respiratory syndrome coronavirus nonstructural protein nsp10/nsp14 exoribonuclease complex,http://dx.doi.org/10.1073/pnas.1201130109,PMC3386072,,,"The replication/transcription complex of severe acute respiratory syndrome coronavirus is composed of at least 16 nonstructural proteins (nsp1–16) encoded by the ORF-1a/1b. This complex includes replication enzymes commonly found in positive-strand RNA viruses, but also a set of RNA-processing activities unique to some nidoviruses. The nsp14 protein carries both exoribonuclease (ExoN) and (guanine-N7)-methyltransferase (N7-MTase) activities. The nsp14 ExoN activity ensures a yet-uncharacterized function in the virus life cycle and must be regulated to avoid nonspecific RNA degradation. In this work, we show that the association of nsp10 with nsp14 stimulates >35-fold the ExoN activity of the latter while playing no effect on N7-MTase activity. Nsp10 mutants unable to interact with nsp14 are not proficient for ExoN activation. The nsp10/nsp14 complex hydrolyzes double-stranded RNA in a 3′ to 5′ direction as well as a single mismatched nucleotide at the 3′-end mimicking an erroneous replication product. In contrast, di-, tri-, and longer unpaired ribonucleotide stretches, as well as 3′-modified RNAs, resist nsp10/nsp14-mediated excision. In addition to the activation of nsp16-mediated 2′-O-MTase activity, nsp10 also activates nsp14 in an RNA processing function potentially connected to a replicative mismatch repair mechanism.",,"['Bouvet, Mickaël', 'Imbert, Isabelle', 'Subissi, Lorenzo', 'Gluais, Laure', 'Canard, Bruno', 'Decroly, Etienne']",,,,
,PMC,Phosphatidylinositol 4-kinases: hostages harnessed to build panviral replication platforms,http://dx.doi.org/10.1016/j.tibs.2012.03.004,PMC3389303,,,"Several RNA viruses have recently been shown to hijack members of the host phosphatidylinositol (PtdIns) 4-kinase (PI4K) family of enzymes. They use PI4K to generate membranes enriched in phosphatidylinositide 4-phosphate (PtdIns4P or PI4P) lipids, which can be used as replication platforms. Viral replication machinery is assembled on these platforms as a supramolecular complex and PtdIns4P lipids regulate viral RNA synthesis. This article highlights these recent studies on the regulation of viral RNA synthesis by PtdIns4P lipids. It explores the potential mechanisms by which PtdIns4P lipids can contribute to viral replication and discusses the therapeutic potential of developing antiviral molecules that target host PI4Ks as a form of panviral therapy.",,"['Altan-Bonnet, Nihal', 'Balla, Tamas']",,,,
,PMC,"Purification, crystallization and preliminary X-ray analysis of nonstructural protein 2 (nsp2) from avian infectious bronchitis virus",http://dx.doi.org/10.1107/S1744309112018623,PMC3370919,,,"Avian infectious bronchitis virus (IBV) is a member of the group III coronaviruses, which differ from the other groups of coronaviruses in that they do not encode the essential pathogenic factor nonstructural protein 1 (nsp1) and instead start with nsp2. IBV nsp2 is one of the first replicase proteins to be translated and processed in the viral life cycle; however, it has an entirely unknown function. In order to better understand the structural details and functional mechanism of IBV nsp2, the recombinant protein was cloned, overexpressed in Escherichia coli, purified and crystallized. The crystals diffracted to 2.8 Å resolution and belonged to space group P2(1), with unit-cell parameters a = 57.0, b = 192.3, c = 105.7 Å, β = 90.8°. Two molecules were found in the asymmetric unit; the Matthews coefficient was 3.9 Å(3) Da(−1), corresponding to a solvent content of 68.2%.",,"['Yu, Kun', 'Ming, Zhenhua', 'Li, Yuanyuan', 'Chen, Cheng', 'Bao, Zehua', 'Ren, Zhilin', 'Liu, Bofeng', 'Tao, Wei', 'Rao, Zihe', 'Lou, Zhiyong']",,,,
,PMC,"Increased density and coverage uniformity of viruses on a sensor surface by using U-type, T-type, and W-type microfluidic devices",http://dx.doi.org/10.1063/1.4722294,PMC3371072,,,"Microorganisms, molecules, or viruses in the fluidic environment are usually at considerably low Reynolds numbers because of small diameters. The viscous forces of molecules and viruses dominate at considerably low Reynolds numbers. This study developed three microfluidic devices, that is, T type, U type, and W type devices, to control the flow movement, which can increase the adhesion density of viruses on the surface of the sensor. The linker 11-mercaptoundecanoic acid (11-MUA) and Turnip yellow mosaic virus (TYMV) were used in this study and measured by a confocal microscope. Fluorescent intensity and coverage of 11-MUA and TYMV were used to identify the adhesion density quantitatively. Results indicate that 11-MUA layers and TYMV disperse randomly by the dipping method. Attachment tests for T-, U-, and W-type devices demonstrated average fluorescence intensities of 1.56, 2.18, and 2.67, respectively, and average fluorescence coverage of 1.31, 1.87, and 2.55 times those of dipping techniques, respectively. The T-type device produced the lowest fluorescence coverage uniformity (10%–80%), whereas the W-type device produced the highest fluorescence coverage uniformity (80%–90%). Fluorescence intensity correlates positively with flow within a specified flow range; however, the exact relationship between fluorescence intensity and flow requires further study. Attachment tests for TYMV virus samples indicated that the W-type device produced an average fluorescence intensity of 3.59 and average fluorescence coverage of 19.13 times greater than those achieved through dipping techniques. Traditional immersion methods achieved fluorescence coverage of 0%–10%, whereas that of the W-type device reached 70%–90%.",,"['Wu, Chia-Che', 'Tseng, Ping-Kuo', 'Tsai, Ching-Hsiu', 'Liu, Yao-Lung']",,,,
,PMC,Inhibition and Avoidance of mRNA Degradation by RNA Viruses,http://dx.doi.org/10.1016/j.mib.2012.04.009,PMC3424362,,,"The cellular mRNA decay machinery plays a major role in regulating the quality and quantity of gene expression in cells. This machinery involves multiple enzymes and pathways that converge to promote the exonucleolytic decay of mRNAs. The transcripts made by RNA viruses are susceptible to degradation by this machinery and, in fact, can be actively targeted. Thus, to maintain gene expression and replication, RNA viruses have evolved a number of strategies to avoid and/or inactivate aspects of the cellular mRNA decay machinery. Recent work uncovering the mechanisms used by RNA viruses to maintain the stability of their transcripts is described below.",,"['Moon, Stephanie L.', 'Barnhart, Michael D.', 'Wilusz, Jeffrey']",,,,
,PMC,The Small Hydrophobic Protein of the Human Respiratory Syncytial Virus Forms Pentameric Ion Channels,http://dx.doi.org/10.1074/jbc.M111.332791,PMC3397895,,,"The small hydrophobic (SH) protein is encoded by the human respiratory syncytial virus. Its absence leads to viral attenuation in the context of whole organisms, and it prevents apoptosis in infected cells. Herein, we have examined the structure of SH protein in detergent micelles and in lipid bilayers, by solution NMR and attenuated total reflection-Fourier transform infrared spectroscopy, respectively. We found that SH protein has a single α-helical transmembrane domain and forms homopentamers in several detergents. In detergent micelles, the transmembrane domain is flanked N-terminally by an α-helix that forms a ring around the lumen of the pore and C-terminally by an extended β-turn. SH protein was found in the plasma membrane of transiently expressing HEK 293 cells, which showed pH-dependent (acid-activated) channel activity. Channel activity was abolished in mutants lacking both native His residues, His(22) and His(51), but not when either His was present. Herein, we propose that the pentameric model of SH protein presented is a physiologically relevant conformation, albeit probably not the only one, in which SH contributes to RSV infection and replication. Viroporins are short (∼100 amino acids) viral membrane proteins that form oligomers of a defined size, act as proton or ion channels, and in general enhance membrane permeability in the host. However, with some exceptions, their precise biological role of their channel activity is not understood. In general, viroporins resemble poorly specialized proteins but are nevertheless critical for viral fitness. In vivo, viruses lacking viroporins usually exhibit an attenuated or weakened phenotype, altered tropism, and diminished pathological effects. We have chosen to study the SH protein, 64 amino acids long, found in the human respiratory syncytial virus because of the effect of RSV on human health and the lack of adequate antivirals. We show that SH protein forms oligomers that behave as ion channels when activated at low pH. This study adds SH protein to a growing group of viroporins that have been structurally characterized. Although the precise biological role of this pentameric channel is still unknown, this report is nevertheless essential to fill some of the many gaps that exist in the understanding of SH protein function.",,"['Gan, Siok-Wan', 'Tan, Edward', 'Lin, Xin', 'Yu, Dejie', 'Wang, Juejin', 'Tan, Gregory Ming-Yeong', 'Vararattanavech, Ardcharaporn', 'Yeo, Chiew Ying', 'Soon, Cin Huang', 'Soong, Tuck Wah', 'Pervushin, Konstantin', 'Torres, Jaume']",,,,
,PMC,Role of Host Reticulon Proteins in Rearranging Membranes for Positive-strand RNA Virus Replication,http://dx.doi.org/10.1016/j.mib.2012.04.007,PMC3670673,,,"Positive-strand RNA [(+)RNA] viruses are responsible for numerous human, animal, and plant diseases. Because of the limiting coding capacity of (+)RNA viruses, their replication requires a complex orchestration of interactions between the viral genome, viral proteins and exploited host factors. To replicate their genomic RNAs, (+)RNA viruses induce membrane rearrangements that create membrane-linked RNA replication compartments. Along with substantial advances on the ultrastructure of the membrane-bound RNA replication compartments, recent results have shed light into the role that host factors play in rearranging these membranes. This review focuses on recent insights that have driven a new understanding of the role that the membrane-shaping host reticulon homology domain proteins (RHPs) play in facilitating the replication of various (+)RNA viruses.",,"['Diaz, Arturo', 'Ahlquist, Paul']",,,,
,PMC,"Comparative In Vivo Analysis of the Nsp15 Endoribonuclease of Murine, Porcine and Severe Acute Respiratory Syndrome Coronaviruses",http://dx.doi.org/10.1016/j.virusres.2012.05.006,PMC3539826,,,"The purpose of this study was to compare the biochemical and biological properties of nonstructural protein (nsp) 15 among mouse hepatitis virus (MHV), severe acute respiratory syndrome coronavirus (SARS-CoV) and transmissible gastroenteritis virus (TGEV) in virus-infected and ectopically expressed cells. In virus-infected cells, MHV nsp15 distributed unevenly throughout the cytoplasm but predominantly in the perinuclear region. When expressed as N-terminal enhanced green fluorescence protein (EGFP) fusion, it predominantly formed speckles in the cytoplasm. In contrast, SARS-CoV and TGEV EGFP-nsp15s distributed smoothly in the whole cell and did not form speckles. Deletion mapping experiments identified two domains responsible for the speckle formation in MHV EGFP-nsp15: Domain I (aa101–150) and Domain III (aa301–374). Interestingly, Domain II (aa151–250) had an inhibitory effect on Domain III- but not Domain I-mediated speckle formation. Expression of a small (35aa) sequence in Domain III alone was sufficient to form speckles for all 3 viral nsp15s. However, addition of surrounding sequences in Domain III abolished the speckle formation for TGEV nsp15 but not for MHV and SARS-CoV nsp15s. Further domain swapping experiments uncovered additional speckle-inducing and -suppressive elements in nsp15s of SARS-CoV and TGEV. Homotypic interaction involving Domain III of MHV nsp15 was further demonstrated biochemically. Moreover, the biological functions of the expressed nsp15s were assessed in MHV-infected cells. It was found that the effects of EGFP-nsp15s on MHV replication were both virus species- and nsp15 domain-dependent. Collectively these results thus underscore the differential biochemical and biological functions among the nsp15s of MHV, TGEV and SARS-CoV in host cells.",,"['Cao, Jianzhong', 'Zhang, Xuming']",,,,
,PMC,Characterization of a recombinant canine coronavirus with a distinct receptor-binding (S1) domain,http://dx.doi.org/10.1016/j.virol.2012.04.013,PMC3377836,,,"Canine alphacoronaviruses (CCoV) exist in two serotypes, type I and II, both of which can cause severe gastroenteritis. Here, we characterize a canine alphacoronavirus, designated CCoV-A76, first isolated in 1976. Serological studies show that CCoV-A76 is distinct from other CCoVs, such as the prototype CCoV-1-71. Efficient replication of CCoV-A76 is restricted to canine cell lines, in contrast to the prototypical type II strain CCoV-1-71 that more efficiently replicates in feline cells. CCoV-A76 can use canine aminopeptidase N (cAPN) receptor for infection of cells, but was unable to use feline APN (fAPN). In contrast, CCoV-1-71 can utilize both. Genomic analysis shows that CCoV-A76 possesses a distinct spike, which is the result of a recombination between type I and type II CCoV, that occurred between the N- and C-terminal domains (NTD and C-domain) of the S1 subunit. These data suggest that CCoV-A76 represents a recombinant coronavirus form, with distinct host cell tropism.",,"['Regan, Andrew D.', 'Millet, Jean K.', 'Tse, Long Ping V.', 'Chillag, Zach', 'Rinaldi, Vera D.', 'Licitra, Beth N.', 'Dubovi, Edward J.', 'Town, Christopher D.', 'Whittaker, Gary R.']",,,,
,PMC,Recent insights into pulmonary repair following virus-induced inflammation of the respiratory tract,http://dx.doi.org/10.1016/j.coviro.2012.04.006,PMC3378727,,,"A hallmark of infection by respiratory viruses is productive infection of and the subsequent destruction of the airway epithelium. These viruses can also target other stromal cell types as well as in certain instances, CD45(+) hematopoietic cells either resident in the lungs or part of the inflammatory response to infection. The mechanisms by which the virus produces injury to these cell types include direct infection with cytopathic effects as a consequence of replication. Host mediated damage is also a culprit in pulmonary injury as both innate and adaptive immune cells produce soluble and cell-associated pro-inflammatory mediators. Recently, it has become increasingly clear that in addition to control of excess inflammation and virus elimination, the resolution of infection requires an active repair process, which is necessary to regain normal respiratory function and restore the lungs to homeostasis. The repair response must re-establish the epithelial barrier and regenerate the microarchitecture of the lung. Emerging areas of research have highlighted the importance of innate immune cells, particularly the newly described innate lymphoid cells, as well as alternatively activated macrophages and pulmonary stem cells in the repair process. The mechanisms by which respiratory viruses may impede or alter the repair response will be important areas of research for identifying therapeutic targets aimed at limiting virus and host mediated injury and expediting recovery.",,"['Gorski, Stacey A.', 'Hufford, Matthew M.', 'Braciale, Thomas J.']",,,,
,PMC,Pandemic 2009 influenza A (H1N1) infection among 2009 Hajj Pilgrims from Southern Iran: a real‐time RT‐PCR‐based study,http://dx.doi.org/10.1111/j.1750-2659.2012.00381.x,PMC4941702,,,"Please cite this paper as: Ziyaeyan et al. (2012) Pandemic 2009 influenza A H1N1 infection among 2009 Hajj Pilgrims from Southern Iran: a real‐time RT‐PCR‐based study. Influenza and Other Respiratory Viruses 6(601), e80–e84. Background  Hajj is a mass gathering undertaken annually in Mecca, Saudi Arabia. The 2009 Hajj coincided with both the pandemic influenza A/H1N1 2009 (A(H1N1)pdm09) and seasonal types of influenza A viruses. The interaction between pandemic influenza and Hajj could cause both a high level of mortality among the pilgrims and the spread of infection in their respective countries upon their return home. Objective  The present study attempted to determine the point prevalence of A(H1N1)pdm09 among returning Iranian pilgrims, most of whom had been vaccinated for seasonal influenza but not A(H1N1)pdm09. Methods  Pharyngeal swabs were collected from 305 pilgrims arriving at the airport in Shiraz, Iran. RNA was extracted from the samples and A(H1N1)pdm09 and other seasonal influenza A viruses were detected using TaqMan real‐time PCR. For A(H1N1)pdm09‐positive samples, the sensitivity to oseltamivir was also evaluated. Results  Subjects included 132 (43·3%) men and 173 (56·7%) women, ranging in age from 24 to 65 years. The A(H1N1)pdm09 virus was detected in five (1·6%) pilgrims and other influenza A viruses in eight (2·6%). All the A(H1N1)pdm09 were sensitive to oseltamivir. Conclusions  Only five cases were found to be positive for A(H1N1)pdm09, and it seems unlikely that the arrival of infected pilgrims to their homelands would cause an outbreak of a new wave of infection there. Thus, the low morbidity and mortality rates among the pilgrims could be attributed to the characteristics of A(H1N1)pdm09, which causes morbidity and mortality in a way similar to the seasonal influenza infections, absence of high‐risk individuals among the Iranian pilgrims, and the instructions given to them about contact and hand hygiene, and respiratory etiquette.",,"['Ziyaeyan, Mazyar', 'Alborzi, Abdolvahab', 'Jamalidoust, Marziyeh', 'Moeini, Mahsa', 'Pouladfar, Gholam R.', 'Pourabbas, Bahman', 'Namayandeh, Mandana', 'Moghadami, Mohsen', 'Bagheri‐Lankarani, Kamran', 'Mokhtari‐Azad, Talat']",,,,
,PMC,"Disease-Drug Pairs Revealed by Computational Genomic Connectivity Mapping on GBA1 Deficient, Gaucher Disease Mice",http://dx.doi.org/10.1016/j.bbrc.2012.05.027,PMC3377787,,,"We have reported that, in addition to recapitulating the classical human Gaucher disease (GD1) phenotype, deletion of the glucocerebrosidase (GBA1) gene in mice results in the dysfunction of a diverse population of immune cells. Most of immune-related, non-classical features of GD1, including gammopathies and autoimmune diathesis, are resistant to macrophage-directed therapies. This has prompted a search for newer agents for human GD1. Here, we used high-density microarray on splenic and liver cells from affected GBA1(−/−) mice to establish a gene “signature”, which was then utilized to interrogate the Broad Institute database, CMAP. Computational connectivity mapping of disease and drug pairs through CMAP revealed several highly enriched, non-null, mimic and anti-mimic hits. Most notably, two compounds with anti-helminthic properties, namely albendazole and oxamniquine, were identified; these are particularly relevant for future testing as the expression of chitinases is enhanced in GD1.",,"['Yuen, Tony', 'Iqbal, Jameel', 'Zhu, Ling-Ling', 'Sun, Li', 'Lin, Aiping', 'Zhao, Hongyu', 'Liu, Jun', 'Mistry, Pramod K.', 'Zaidi, Mone']",,,,
,PMC,Co-infection of porcine dendritic cells with porcine circovirus type 2a (PCV2a) and genotype II porcine reproductive and respiratory syndrome virus (PRRSV) induces CD4(+)CD25(+)FoxP3(+) T cells in vitro,http://dx.doi.org/10.1016/j.vetmic.2012.04.040,PMC3443269,,,"Porcine circovirus associated disease (PCVAD) is currently one of the most economically important diseases in the global swine industry. Porcine circovirus type 2 (PCV2) is the primary causative agent, however co-infection with other swine pathogens such as porcine reproductive and respiratory syndrome virus (PRRSV) is often required to induce the full spectrum of clinical PCVAD. While the specific mechanisms of viral co-infection that lead to clinical disease are not fully understood, immune modulation by the co-infecting viruses likely plays a critical role. We evaluated the ability of dendritic cells (DC) infected with PRRSV, PCV2 or both to induce regulatory T cells (T(regs)) in vitro. DCs infected with PCV2 significantly increased CD4(+)CD25(+)FoxP3(+) T(regs) (p<0.05) and DCs co-infected with PRRSV and PCV2 induced significantly higher numbers of T(regs) than with PCV2 alone (p<0.05). Cytokine analysis indicated that the induction of T(regs) by co-infected DCs may be dependent on TGF-β and not IL-10. Our data support the immunomodulatory role of PCV2/PRRSV co-infection in the pathogenesis of PCVAD, specifically via T(reg) mediated immunosuppression.",,"['Cecere, T.E.', 'Meng, X.J.', 'Pelzer, K.', 'Todd, S.M.', 'Beach, N.M.', 'Ni, Y.Y.', 'LeRoith, T.']",,,,
,PMC,Characterization of the immune responses elicited by baculovirus-based vector vaccines against influenza virus hemagglutinin,http://dx.doi.org/10.1038/aps.2012.23,PMC4010374,,,"AIM: To compare the specific immune responses elicited by different baculovirus vectors in immunized mice. METHODS: We constructed and characterized two recombinant baculoviruses carrying the expression cassette for the H5N1 influenza virus hemagglutinin (HA) gene driven by either an insect cell promoter (vAc-HA) or a dual-promoter active both in insect and mammalian cells (vAc-HA-DUAL). Virus without the HA gene (vAc-EGFP) was used as a control. These viruses were used to immunize mice subcutaneously and intraperitoneally. The production of total and specific antibodies was determined by ELISA and competitive ELISA. Cytokine production by the spleen cells of immunized mice was studied using the ELISPOT assay. RESULTS: Both the vAc-HA and vAc-HA-DUAL vectors expressed HA proteins in insect Sf9 cells, and HA antigen was present in progeny virions. The vAc-HA-DUAL vector also mediated HA expression in virus-transduced mammalian cell lines (BHK and A547). Both vAc-HA and vAc-HA-DUAL exhibited higher transduction efficiencies than vAc-EGFP in mammalian cells, as shown by the expression of the reporter gene egfp. Additionally, both vAc-HA and vAc-HA-DUAL induced high levels of HA-specific antibody production in immunized mice; vAc-HA-DUAL was more efficient in inducing IFN-γ and IL-2 upon stimulation with specific antigen, whereas vAc-HA was more efficient in inducing IL-4 and IL-6. CONCLUSION: Baculovirus vectors elicited efficient, specific immune responses in immunized mice. The vector displaying the HA antigen on the virion surface (vAc-HA) elicited a Th2-biased immune response, whereas the vector displaying HA and mediating HA expression in the cell (vAc-HA-DUAL) elicited a Th1-biased immune response.",,"['Hu, Zhi-peng', 'Yin, Juan', 'Zhang, Yuan-yuan', 'Jia, Shu-ya', 'Chen, Zuo-jia', 'Zhong, Jiang']",,,,
,PMC,Deriving behavior model parameters from survey data: Self-protective behavior adoption during the 2009–2010 Influenza A(H1N1) pandemic,http://dx.doi.org/10.1111/j.1539-6924.2012.01823.x,PMC3755610,,,"In this paper, we demonstrate how public opinion surveys can be designed to collect information pertinent to computational behavior modeling, and we present the results of a public opinion and behavior survey conducted during the 2009–2010 H1N1 influenza pandemic. The results are used to parameterize the Health Belief Model of individual health-protective decision making. Survey subjects were asked questions about their perceptions of the then-circulating influenza and attitudes towards two personal protective behaviors: vaccination and avoidance of crowds. We empirically address two important issues in applying the Health Belief Model of behavior to computational infectious disease simulation: (1) the factors dynamically influencing the states of the Health Belief Model variables and (2) the appropriateness of the Health Belief Model in describing self-protective behavior in the context of pandemic influenza.",,"['Durham, David P.', 'Casman, Elizabeth A.', 'Albert, Steven M.']",,,,
,PMC,High Titers of IgE Antibody to Dust Mite Allergen and the Risk for Wheezing Among Asthmatic Children Infected with Rhinovirus,http://dx.doi.org/10.1016/j.jaci.2012.03.040,PMC3792652,,,"BACKGROUND: The relevance of allergic sensitization, judged by titers of serum IgE antibodies, to the risk of an asthma exacerbation caused by rhinovirus is unclear. OBJECTIVE: To examine the prevalence of rhinovirus infections in relation to the atopic status of children treated for wheezing in Costa Rica, a country with an increased asthma burden. METHODS: The children enrolled (n=287) were 7 through 12 years old. They included 96 with acute wheezing, 65 with stable asthma, and 126 non-asthmatic controls. PCR methods, including gene sequencing to identify rhinovirus strains, were used to identify viral pathogens in nasal washes. Results were examined in relation to wheezing, total IgE, allergen-specific IgE antibody, and levels of expired nitric oxide (FE(NO)). RESULTS: Sixty-four percent of wheezing children compared to 13% of children with stable asthma and 17% of the non-asthmatic controls tested positive for rhinovirus (p<0.001 for both comparisons). Among wheezing subjects, 75% of the rhinoviruses detected were Group C strains. High titers of IgE antibodies to dust mite allergen (especially Dermatophagoides sp) were common and correlated significantly with levels of total IgE and FE(NO). The greatest risk for wheezing was observed among children with titers of IgE antibodies to dust mite ≥17.5 IU/ml who tested positive for rhinovirus (odds ratio for wheezing: 31.5; 95% CI 8.3–108, p<0.001). CONCLUSIONS: High titers of IgE antibody to dust mite allergen were common and significantly increased the risk for acute wheezing provoked by rhinovirus among asthmatic children.",,"['Soto-Quiros, Manuel', 'Avila, Lydiana', 'Platts-Mills, Thomas AE', 'Hunt, John F.', 'Erdman, Dean D.', 'Carper, Holliday', 'Murphy, Deborah D.', 'Odio, Silvia', 'James, Hayley R.', 'Patrie, James T.', 'Hunt, William', 'O’Rourke, Ashli K.', 'Davis, Michael D.', 'Steinke, John W.', 'Lu, Xiaoyan', 'Kennedy, Joshua', 'Heymann, Peter W.']",,,,
,PMC,Structural insights into RNA recognition and activation of RIG-I-like receptors,http://dx.doi.org/10.1016/j.sbi.2012.03.011,PMC3383332,,,"RIG-I like receptors (RLR) that recognize non-self RNA play critical roles in activating host innate immune pathways in response to viral infections. Not surprisingly, RLRs and their associated signaling networks are also targeted by numerous antagonists that facilitate viral pathogenesis. Although the role of RLRs in orchestrating antiviral signaling has been recognized for some time, our knowledge of the complex regulatory mechanisms that control signaling through these key molecules is incomplete. A series of recent structural studies shed new light into the structural basis for dsRNA recognition and activation of RLRs. Collectively, these studies suggest that the repression of RLRs is facilitated by a cis element that makes multiple contacts with domains within the helicase and that RNA binding initiated by the C-terminal RNA binding domain is important for ATP hydrolysis and release of the CARD domain containing signaling module from the repressed conformation. These studies also highlight potential differences between RIG-I and MDA5, two RLR members. Together with previous studies, these new results bring us a step closer to uncovering the complex regulatory process of a key protein that protects host cells from invading pathogens.",,"['Leung, Daisy W.', 'Amarasinghe, Gaya K.']",,,,
,PMC,LPS-Stimulated Cytokine Production in Type I Cells Is Modulated by the Renin–Angiotensin System,http://dx.doi.org/10.1165/rcmb.2011-0289OC,PMC3359899,,,"The alveolar epithelium serves as a barrier to the entry of potential respiratory pathogens. Alveolar Type II (TII) cells have immunomodulatory functions, but whether Type I (TI) cells, which comprise approximately 95% of the alveolar epithelium, also play a role in immunity is unknown. Because the renin–angiotensin system (RAS) is emerging as an important mediator of inflammation, and angiotensin-converting enzyme 2 (ACE2), an element of the RAS, has been implicated in lung injury, we hypothesize that TI cells can produce cytokines in response to LPS stimulation, and that this inflammation can be modulated by the RAS. Alveolar TI cells were isolated from adult Sprague-Dawley rat lungs that had been injured with an intratracheal instillation of LPS. PCR was performed to determine whether TI cells expressed transcripts for TNF-α, IL-6, or IL-1β at baseline and after lung injury. Immunocytochemical and protein analysis detected angiotensin II (Ang II) and ACE2, as well as angiotensin Type 1 receptor (AT1R) and Type 2 receptor (AT2R), in TI cells. To separate cell-specific responses, primary TI cells were isolated, cultured, and exposed to LPS, Ang II, or specific inhibitors of AT1R or AT2R. Cytokine production was assayed by ELISA. LPS stimulated the production of all cytokines, whereas ACE2 and losartan, an AT1R inhibitor, blocked elements of the LPS-induced cytokine response. Primary TI cells produce cytokines when treated with LPS, contain important components of the RAS, and can modulate LPS-induced cytokine production via the RAS, suggesting a role for TI cells in the innate immune response of the lung.",,"['Wong, Mandi H.', 'Chapin, Olivia C.', 'Johnson, Meshell D.']",,,,
,PMC,Identification of serotype-specific T cell responses to highly conserved regions of the dengue viruses,http://dx.doi.org/10.1111/j.1365-2249.2012.04566.x,PMC3390523,,,"Determining previous infecting dengue virus (DENV) serotypes has been difficult due to highly cross-reactive immune responses from previous DENV infections. Determining the correlates of serotype-specific immune responses would be crucial in understanding dengue transmission in the community and would also help to determine the correlates of protective immune responses. Therefore, we set out to define highly conserved, serotype-specific regions of the DENVs. Serotype-specific and highly conserved regions of the four DENV serotypes were identified using Basic Local Alignment Search Tool (BLAST) searches and custom perl scripts. Using ex-vivo and cultured enzyme-linked immunospot (ELISPOT) assays, we identified serotype-specific T cell epitopes within the four DENV serotypes in healthy adult donors from Sri Lanka. We identified T cell responses to 19 regions of the four DENV serotypes. Six peptides were from the NS2A region and four peptides were from the NS4A region. All immune donors responded to peptides of at least two DENV serotypes, suggesting that heterologous infection is common in Sri Lanka. Eight of 20 individuals responded to at least two peptides of DENV-4, despite this serotype not being implicated previously in any of the epidemics in Sri Lanka. The use of these regions to determine past and current infecting DENV serotypes will be of value to characterize further the dynamics of silent dengue transmission in the community. In addition, these T cell responses to these regions could be used to characterize DENV serotype-specific immune responses and thus possibly help us to understand the immune correlates of a protective immune response.",,"['Malavige, G N', 'McGowan, S', 'Atukorale, V', 'Salimi, M', 'Peelawatta, M', 'Fernando, N', 'Jayaratne, S D', 'Ogg, G']",,,,
,PMC,"Enterovirus 104 Infection in Adult, Japan, 2011",http://dx.doi.org/10.3201/eid1805.111890,PMC3358046,22516422,NO-CC CODE,,2012 May,"['Kaida, Atsushi', 'Kubo, Hideyuki', 'Sekiguchi, Jun-ichiro', 'Hase, Atsushi', 'Iritani, Nobuhiro']",Emerg Infect Dis,,,
,PMC,"Foxp3(+) regulatory T cells, immune stimulation and host defence against infection",http://dx.doi.org/10.1111/j.1365-2567.2011.03551.x,PMC3372751,,,"The immune system is intricately regulated allowing potent effectors to expand and become rapidly mobilized after infection, while simultaneously silencing potentially detrimental responses that averts immune-mediated damage to host tissues. This relies in large part on the delicate interplay between immune suppressive regulatory CD4(+) T (Treg) cells and immune effectors that without active suppression by Treg cells cause systemic and organ-specific autoimmunity. Although these beneficial roles have been classically described as counterbalanced by impaired host defence against infection, newfound protective roles for Treg cells against specific viral pathogens (e.g. herpes simplex virus 2, lymphocytic choriomeningitis virus, West Nile virus) have been uncovered using transgenic mice that allow in vivo Treg-cell ablation based on Foxp3 expression. In turn, Foxp3(+) Treg cells also provide protection against some parasitic (Plasmodium sp., Toxoplasma gondii) and fungal (Candida albicans) pathogens. By contrast, for bacterial and mycobacterial infections (e.g. Listeria monocytogenes, Salmonella enterica, Mycobacterium tuberculosis), experimental manipulation of Foxp3(+) cells continues to indicate detrimental roles for Treg cells in host defence. This variance is probably related to functional plasticity in Treg cell suppression that shifts discordantly following infection with different types of pathogens. Furthermore, the efficiency whereby Treg cells silence immune activation coupled with the plasticity in Foxp3(+) cell activity suggest that overriding Treg-mediated suppression represents a prerequisite ‘signal zero’ that together with other stimulation signals [T-cell receptor (signal 1), co-stimulation (signal 2), inflammatory cytokines (signal 3)] are essential for T-cell activation in vivo. Herein, the importance of Foxp3(+) Treg cells in host defence against infection, and the significance of infection-induced shifts in Treg-cell suppression are summarized.",,"['Rowe, Jared H', 'Ertelt, James M', 'Way, Sing Sing']",,,,
,PMC,Cross-comparison of Protein Recognition of Sialic Acid Diversity on Two Novel Sialoglycan Microarrays,http://dx.doi.org/10.1074/jbc.M112.359323,PMC3391140,,,"DNA and protein arrays are commonly accepted as powerful exploratory tools in research. This has mainly been achieved by the establishment of proper guidelines for quality control, allowing cross-comparison between different array platforms. As a natural extension, glycan microarrays were subsequently developed, and recent advances using such arrays have greatly enhanced our understanding of protein-glycan recognition in nature. However, although it is assumed that biologically significant protein-glycan binding is robustly detected by glycan microarrays, there are wide variations in the methods used to produce, present, couple, and detect glycans, and systematic cross-comparisons are lacking. We address these issues by comparing two arrays that together represent the marked diversity of sialic acid modifications, linkages, and underlying glycans in nature, including some identical motifs. We compare and contrast binding interactions with various known and novel plant, vertebrate, and viral sialic acid-recognizing proteins and present a technical advance for assessing specificity using mild periodate oxidation of the sialic acid chain. These data demonstrate both the diversity of sialic acids and the analytical power of glycan arrays, showing that different presentations in different formats provide useful and complementary interpretations of glycan-binding protein specificity. They also highlight important challenges and questions for the future of glycan array technology and suggest that glycan arrays with similar glycan structures cannot be simply assumed to give similar results.",,"['Padler-Karavani, Vered', 'Song, Xuezheng', 'Yu, Hai', 'Hurtado-Ziola, Nancy', 'Huang, Shengshu', 'Muthana, Saddam', 'Chokhawala, Harshal A.', 'Cheng, Jiansong', 'Verhagen, Andrea', 'Langereis, Martijn A.', 'Kleene, Ralf', 'Schachner, Melitta', 'de Groot, Raoul J.', 'Lasanajak, Yi', 'Matsuda, Haruo', 'Schwab, Richard', 'Chen, Xi', 'Smith, David F.', 'Cummings, Richard D.', 'Varki, Ajit']",,,,
,PMC,Development of a Loop-Mediated Isothermal Amplification Assay for Rapid Detection of Capripoxviruses,http://dx.doi.org/10.1128/JCM.06796-11,PMC3347125,,,"Sheep pox (SP), goat pox (GP), and lumpy skin disease (LSD), caused by capripoxviruses (CaPVs), are economically important diseases of sheep, goats, and cattle, respectively. Here, we report the development of a loop-mediated isothermal amplification (LAMP) assay for rapid detection of CaPVs. LAMP primers were designed to target a conserved gene encoding the poly(A) polymerase small subunit (VP39) of CaPVs. Hydroxynaphthol blue (HNB) was incorporated to monitor assay progress by color change from violet when negative to sky blue when positive, and results were verified by agarose gel electrophoresis. The LAMP assay was shown to be highly specific for CaPVs, with no apparent cross-reactivity to other related viruses (near neighbors) or viruses that cause similar clinical signs (look-a-like viruses). The performance of LAMP was compared to that of a highly sensitive quantitative real-time PCR (qPCR) assay. LAMP and qPCR exhibited similar analytical sensitivities, with limits of detection of 3 and 8 viral genome copies, respectively. Diagnostic specificity was assessed on 36 negative specimens, including swabs and EDTA blood from control sheep, goats, and cattle. Diagnostic sensitivity was assessed on 275 specimens, including EDTA blood, swabs, and tissues from experimentally infected sheep, goats, and cattle. Overall agreement on diagnostic test results between the two assays was 90 to 95% for specificity and 89 to 100% for sensitivity. The LAMP assay described in this report is simple to use, inexpensive, highly sensitive, and particularly well suited for the diagnosis of capripox in less well equipped laboratories and in rural settings where resources are limited.",,"['Das, Amaresh', 'Babiuk, Shawn', 'McIntosh, Michael T.']",,,,
,PMC,Sensitive and Rapid Detection of the New Delhi Metallo-Beta-Lactamase Gene by Loop-Mediated Isothermal Amplification,http://dx.doi.org/10.1128/JCM.06647-11,PMC3347096,,,"New Delhi metallo-β-lactamase 1 (NDM-1), which is associated with resistance to carbapenem, was first reported in 2008. A sensitive and rapid molecular assay to detect the plasmid bla(NDM-1) in clinical isolates is needed to control its spread. We describe a loop-mediated isothermal amplification (LAMP) assay for the rapid detection of bla(NDM-1) from pure culture and sputum, urine, and fecal samples. Eight sets of primers were designed to recognize six or eight distinct sequences on target bla(NDM-1), and one set was selected as the most appropriate set of primers for its rapid detection. The specificity and sensitivity of the primers in the LAMP reactions for bla(NDM-1) detection were determined. The sensitivity of the LAMP assay for bla(NDM-1) detection in sputum, urine, and fecal samples was also tested. Two methods, namely, monitoring of turbidity and addition of calcein to the reaction tube, were used to determine negative and positive results. The results showed that target DNA was amplified and visualized by the two detection methods within 70 min at an isothermal temperature of 65°C. The sensitivity of LAMP, with a detection limit of 10.70 pg/μl DNA, was 100-fold greater than that of PCR. Thirteen infection bacterial strains without bla(NDM-1) were selected for testing of specificity, and the results of the amplification were negative, which showed that the primers had good levels of specificity. The LAMP method reported here is demonstrated to be a potentially valuable means for the detection of bla(NDM-1) and rapid clinical diagnosis, being fast, simple, and low in cost.",,"['Liu, Wei', 'Zou, Dayang', 'Li, Yan', 'Wang, Xuesong', 'He, Xiang', 'Wei, Xiao', 'Shao, Changlin', 'Li, Xuelian', 'Shang, Wei', 'Yu, Kaitao', 'Liu, Dawei', 'Li, Yunmei', 'Guo, Jing', 'Yin, Zhitao', 'Yuan, Jing']",,,,
,PMC,"Diabetes, Insulin Resistance, and Metabolic Syndrome in Horses",,PMC3440056,,,"Analogous to the situation in human medicine, contemporary practices in horse management, which incorporate lengthy periods of physical inactivity coupled with provision of nutritional rations characterized by inappropriately high sugar and starch, have led to obesity being more commonly recognized by practitioners of equine veterinary practice. In many of these cases, obesity is associated with insulin resistance (IR) and glucose intolerance. An equine metabolic syndrome (MS) has been described that is similar to the human MS in that both IR and aspects of obesity represent cornerstones of its definition. Unlike its human counterpart, identification of the equine metabolic syndrome (EMS) portends greater risk for development of laminitis, a chronic, crippling affliction of the equine hoof. When severe, laminitis sometimes necessitates euthanasia. Unlike the human condition, the risk of developing type 2 diabetes mellitus and many other chronic conditions, for which the risk is recognized as increased in the face of MS, is less likely in horses. The equine veterinary literature has been replete with reports of scientific investigations regarding the epidemiology, pathophysiology, and treatment of EMS.",,"['Johnson, Philip J.', 'Wiedmeyer, Charles E.', 'LaCarrubba, Alison', 'Ganjam, V. K. (Seshu)', 'Messer, Nat T.']",,,,
,PMC,Temperature-Sensitive Mutants and Revertants in the Coronavirus Nonstructural Protein 5 Protease (3CLpro) Define Residues Involved in Long-Distance Communication and Regulation of Protease Activity,http://dx.doi.org/10.1128/JVI.06754-11,PMC3347385,,,"Positive-strand RNA virus genomes are translated into polyproteins that are processed by viral proteases to yield functional intermediate and mature proteins. Coronaviruses (CoVs) carry genes that encode an nsp5 protease (also known as 3CLpro or Mpro) responsible for 11 maturation cleavages. The nsp5 structure contains two chymotrypsin-like domains (D1 and D2) and a unique domain (D3), and forms functional dimers. However, little is known of interactions or communication across the structure of the protease during nsp5 activity. Using reverse genetic mutagenesis of the CoV murine hepatitis virus (MHV) nsp5, we identified a new temperature-sensitive (ts) mutation in D2 of nsp5 (Ser133Ala) and confirmed a ts residue in D3 (Phe219Leu). Both D2-tsS133A and D3-tsF219L were impaired for viral replication and nsp5-mediated polyprotein processing at the nonpermissive temperature. Passage of tsS133A and tsF219L at the nonpermissive temperature resulted in emergence of multiple second-site suppressor mutations, singly and in combinations. Among the second-site mutations, a D2 His134Tyr change suppressed the ts phenotype of D2-tsS133A and D3-tsF219L, as well as the previously reported D2-tsV148A. Analysis of multiple CoV nsp5 structures, and alignment of nonredundant nsp5 primary sequences, demonstrated that ts and suppressor residues are not conserved across CoVs and are physically distant (>10 Å) from each other, from catalytic and substrate-binding residues, and from the nsp5 dimer interface. These findings demonstrate that long-distance communication pathways between multiple residues and domains of nsp5 play a significant role in nsp5 activity and viral replication, suggesting possible novel targets for non-active site inhibitors of nsp5.",,"['Stobart, Christopher C.', 'Lee, Alice S.', 'Lu, Xiaotao', 'Denison, Mark R.']",,,,
,PMC,Genetic Divergence of Rotavirus Nonstructural Protein 4 Results in Distinct Serogroup-Specific Viroporin Activity and Intracellular Punctate Structure Morphologies,http://dx.doi.org/10.1128/JVI.06759-11,PMC3347366,,,"Nonstructural protein 4 (NSP4) viroporin activity is critical for the replication and assembly of serogroup A rotavirus (RVA); however, the dramatic primary sequence divergence of NSP4s across serogroups raises the possibility that viroporin activity is not a common feature among RVs. We tested for NSP4 viroporin activity from divergent strains, including RVA (EC and Ty-1), RVB (IDIR), and RVC (Cowden). Canonical viroporin motifs were identified in RVA, RVB, and RVC NSP4s, but the arrangement of basic residues and the amphipathic α-helices was substantially different between serogroups. Using Escherichia coli and mammalian cell expression, we showed that each NSP4 tested had viroporin activity, but serogroup-specific viroporin phenotypes were identified. Only mammalian RVA and RVC NSP4s induced BL21-pLysS E. coli cell lysis, a classical viroporin activity assay. In contrast, RVA, RVB, and RVC NSP4 expression was universally cytotoxic to E. coli and disrupted reduction-oxidation activities, as measured by a new redox dye assay. In mammalian cells, RVB and RVC NSP4s were initially localized in the endoplasmic reticulum (ER) and trafficked into punctate structures that were mutually exclusive with RVA NSP4. The punctate structures partially localized to the ER-Golgi intermediate compartment (ERGIC) but primarily colocalized with punctate LC3, a marker for autophagosomes. Similar to RVA NSP4, expression of RVB and RVC NSP4s significantly elevated cytosolic calcium levels, demonstrating that despite strong primary sequence divergence, RV NSP4 has maintained viroporin activity across serogroups A to C. These data suggest that elevated cytosolic calcium is a common critical process for all rotavirus strains.",,"['Hyser, Joseph M.', 'Utama, Budi', 'Crawford, Sue E.', 'Estes, Mary K.']",,,,
,PMC,"Posttranslational Modification of Vesicular Stomatitis Virus Glycoprotein, but Not JNK Inhibition, Is the Antiviral Mechanism of SP600125",http://dx.doi.org/10.1128/JVI.06649-11,PMC3347359,,,"Vesicular stomatitis virus (VSV), a negative-sense single-stranded-RNA rhabdovirus, is an extremely promising oncolytic agent for cancer treatment. Since oncolytic virotherapy is moving closer to clinical application, potentially synergistic combinations of oncolytic viruses and molecularly targeted antitumor agents are becoming a meaningful strategy for cancer treatment. Mitogen-activated protein kinase (MAPK) inhibitors have been shown to impair liver cell proliferation and tumor development, suggesting their potential use as therapeutic agents for hepatocellular carcinoma (HCC). In this work, we show that the impairment of MAPK in vitro did not interfere with the oncolytic properties of VSV in HCC cell lines. Moreover, the administration of MAPK inhibitors did not restore the responsiveness of HCC cells to alpha/beta interferon (IFN-α/β). In contrast to previous reports, we show that JNK inhibition by the inhibitor SP600125 is not responsible for VSV attenuation in HCC cells and that this compound acts by causing a posttranslational modification of the viral glycoprotein.",,"['Marozin, Sabrina', 'Altomonte, Jennifer', 'Apfel, Sibylle', 'Dinh, Phat X.', 'De Toni, Enrico N.', 'Rizzani, Antonia', 'Nüssler, Andreas', 'Kato, Nobuyuki', 'Schmid, Roland M.', 'Pattnaik, Asit K.', 'Ebert, Oliver']",,,,
,PMC,Host Acyl Coenzyme A Binding Protein Regulates Replication Complex Assembly and Activity of a Positive-Strand RNA Virus,http://dx.doi.org/10.1128/JVI.06701-11,PMC3347339,,,"All positive-strand RNA viruses reorganize host intracellular membranes to assemble their replication complexes. Similarly, brome mosaic virus (BMV) induces two alternate forms of membrane-bound RNA replication complexes: vesicular spherules and stacks of appressed double-membrane layers. The mechanisms by which these membrane rearrangements are induced, however, remain unclear. We report here that host ACB1-encoded acyl coenzyme A (acyl-CoA) binding protein (ACBP) is required for the assembly and activity of both BMV RNA replication complexes. ACBP is highly conserved among eukaryotes, specifically binds to long-chain fatty acyl-CoA, and promotes general lipid synthesis. Deleting ACB1 inhibited BMV RNA replication up to 30-fold and resulted in formation of spherules that were ∼50% smaller but ∼4-fold more abundant than those in wild-type (wt) cells, consistent with the idea that BMV 1a invaginates and maintains viral spherules by coating the inner spherule membrane. Furthermore, smaller and more frequent spherules were preferentially formed under conditions that induce layer formation in wt cells. Conversely, cellular karmella structures, which are arrays of endoplasmic reticulum (ER) membranes formed upon overexpression of certain cellular ER membrane proteins, were formed normally, indicating a selective inhibition of 1a-induced membrane rearrangements. Restoring altered lipid composition largely complemented the BMV RNA replication defect, suggesting that ACBP was required for maintaining lipid homeostasis. Smaller and more frequent spherules are also induced by 1a mutants with specific substitutions in a membrane-anchoring amphipathic α-helix, implying that the 1a-lipid interactions play critical roles in viral replication complex assembly.",,"['Zhang, Jiantao', 'Diaz, Arturo', 'Mao, Lan', 'Ahlquist, Paul', 'Wang, Xiaofeng']",,,,
,PMC,Accumulation of Autophagosomes in Semliki Forest Virus-Infected Cells Is Dependent on Expression of the Viral Glycoproteins,http://dx.doi.org/10.1128/JVI.06581-11,PMC3347313,,,"Autophagy is a cellular process that sequesters cargo in double-membraned vesicles termed autophagosomes and delivers this cargo to lysosomes to be degraded. It is enhanced during nutrient starvation to increase the rate of amino acid turnover. Diverse roles for autophagy have been reported for viral infections, including the assembly of viral replication complexes on autophagic membranes and protection of host cells from cell death. Here, we show that autophagosomes accumulate in Semliki Forest virus (SFV)-infected cells. Despite this, disruption of autophagy had no effect on the viral replication rate or formation of viral replication complexes. Also, viral proteins rarely colocalized with autophagosome markers, suggesting that SFV did not utilize autophagic membranes for its replication. Further, we found that SFV infection, unlike nutrient starvation, did not inactivate the constitutive negative regulator of autophagosome formation, mammalian target of rapamycin, suggesting that SFV-dependent accumulation of autophagosomes was not a result of enhanced autophagosome formation. In starved cells, addition of NH(4)Cl, an inhibitor of lysosomal acidification, caused a dramatic accumulation of starvation-induced autophagosomes, while in SFV-infected cells, NH(4)Cl did not further increase levels of autophagosomes. These results suggest that accumulation of autophagosomes in SFV-infected cells is due to an inhibition of autophagosome degradation rather than enhanced rates of autophagosome formation. Finally, we show that the accumulation of autophagosomes in SFV-infected cells is dependent on the expression of the viral glycoprotein spike complex.",,"['Eng, Kai Er', 'Panas, Marc D.', 'Murphy, Deirdre', 'Karlsson Hedestam, Gunilla B.', 'McInerney, Gerald M.']",,,,
,PMC,Evaluation of Pneumonia Virus of Mice as a Possible Human Pathogen,http://dx.doi.org/10.1128/JVI.00163-12,PMC3347304,,,"Pneumonia virus of mice (PVM), a relative of human respiratory syncytial virus (RSV), causes respiratory disease in mice. There is serologic evidence suggesting widespread exposure of humans to PVM. To investigate replication in primates, African green monkeys (AGM) and rhesus macaques (n = 4) were inoculated with PVM by the respiratory route. Virus was shed intermittently at low levels by a subset of animals, suggesting poor permissiveness. PVM efficiently replicated in cultured human cells and inhibited the type I interferon (IFN) response in these cells. This suggests that poor replication in nonhuman primates was not due to a general nonpermissiveness of primate cells or poor control of the IFN response. Seroprevalence in humans was examined by screening sera from 30 adults and 17 young children for PVM-neutralizing activity. Sera from a single child (6%) and 40% of adults had low neutralizing activity against PVM, which could be consistent with increasing incidence of exposure following early childhood. There was no cross-reaction of human or AGM sera between RSV and PVM and no cross-protection in the mouse model. In native Western blots, human sera reacted with RSV but not PVM proteins under conditions in which AGM immune sera reacted strongly. Serum reactivity was further evaluated by flow cytometry using unfixed Vero cells infected with PVM or RSV expressing green fluorescent protein (GFP) as a measure of viral gene expression. The reactivity of human sera against RSV-infected cells correlated with GFP expression, whereas reactivity against PVM-infected cells was low and uncorrelated with GFP expression. Thus, PVM specificity was not evident. Our results indicate that the PVM-neutralizing activity of human sera is not due to RSV- or PVM-specific antibodies but may be due to low-affinity, polyreactive natural antibodies of the IgG subclass. The absence of PVM-specific antibodies and restriction in nonhuman primates makes PVM unlikely to be a human pathogen.",,"['Brock, Linda G.', 'Karron, Ruth A.', 'Krempl, Christine D.', 'Collins, Peter L.', 'Buchholz, Ursula J.']",,,,
,PMC,Complete Genome Sequences of a Korean Virulent Porcine Epidemic Diarrhea Virus and Its Attenuated Counterpart,http://dx.doi.org/10.1128/JVI.00557-12,PMC3347302,,,"A virulent porcine epidemic diarrhea virus (PEDV) strain, DR13, was obtained from suckling pigs suspected of having porcine epidemic diarrhea in 1999 in Korea, and its attenuated counterpart was derived from virulent strain DR13 by serial propagation in Vero cells. This report describes the first complete genome sequences of virulent PEDV and its attenuated counterpart, which will provide important insights into the molecular basis of the attenuation of PEDV.",,"['Park, Seong-Jun', 'Kim, Hye-Kwon', 'Song, Dae-Sub', 'An, Dong-Jun', 'Park, Bong-Kyun']",,,,
,PMC,The Double-Stranded RNA Bluetongue Virus Induces Type I Interferon in Plasmacytoid Dendritic Cells via a MYD88-Dependent TLR7/8-Independent Signaling Pathway,http://dx.doi.org/10.1128/JVI.06716-11,PMC3347300,,,"Dendritic cells (DCs), especially plasmacytoid DCs (pDCs), produce large amounts of alpha/beta interferon (IFN-α/β) upon infection with DNA or RNA viruses, which has impacts on the physiopathology of the viral infections and on the quality of the adaptive immunity. However, little is known about the IFN-α/β production by DCs during infections by double-stranded RNA (dsRNA) viruses. We present here novel information about the production of IFN-α/β induced by bluetongue virus (BTV), a vector-borne dsRNA Orbivirus of ruminants, in sheep primary DCs. We found that BTV induced IFN-α/β in skin lymph and in blood in vivo. Although BTV replicated in a substantial fraction of the conventional DCs (cDCs) and pDCs in vitro, only pDCs responded to BTV by producing a significant amount of IFN-α/β. BTV replication in pDCs was not mandatory for IFN-α/β production since it was still induced by UV-inactivated BTV (UV-BTV). Other inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-12p40, were also induced by UV-BTV in primary pDCs. The induction of IFN-α/β required endo-/lysosomal acidification and maturation. However, despite being an RNA virus, UV-BTV did not signal through Toll-like receptor 7 (TLR7) for IFN-α/β induction. In contrast, pathways involving the MyD88 adaptor and kinases dsRNA-activated protein kinase (PKR) and stress-activated protein kinase (SAPK)/Jun N-terminal protein kinase (JNK) were implicated. This work highlights the importance of pDCs for the production of innate immunity cytokines induced by a dsRNA virus, and it shows that a dsRNA virus can induce IFN-α/β in pDCs via a novel TLR-independent and Myd88-dependent pathway. These findings have implications for the design of efficient vaccines against dsRNA viruses.",,"['Ruscanu, Suzana', 'Pascale, Florentina', 'Bourge, Mickael', 'Hemati, Behzad', 'Elhmouzi-Younes, Jamila', 'Urien, Céline', 'Bonneau, Michel', 'Takamatsu, Haru', 'Hope, Jayne', 'Mertens, Peter', 'Meyer, Gilles', 'Stewart, Meredith', 'Roy, Polly', 'Meurs, Eliane F.', 'Dabo, Stéphanie', 'Zientara, Stéphan', 'Breard, Emmanuel', 'Sailleau, Corinne', 'Chauveau, Emilie', 'Vitour, Damien', 'Charley, Bernard', 'Schwartz-Cornil, Isabelle']",,,,
,PMC,"Tacaribe Virus Causes Fatal Infection of An Ostensible Reservoir Host, the Jamaican Fruit Bat",http://dx.doi.org/10.1128/JVI.00201-12,PMC3347293,,,"Tacaribe virus (TCRV) was first isolated from 11 Artibeus species bats captured in Trinidad in the 1950s during a rabies virus surveillance program. Despite significant effort, no evidence of infection of other mammals, mostly rodents, was found, suggesting that no other vertebrates harbored TCRV. For this reason, it was hypothesized that TCRV was naturally hosted by artibeus bats. This is in stark contrast to other arenaviruses with known hosts, all of which are rodents. To examine this hypothesis, we conducted experimental infections of Jamaican fruit bats (Artibeus jamaicensis) to determine whether they could be persistently infected without substantial pathology. We subcutaneously or intranasally infected bats with TCRV strain TRVL-11573, the only remaining strain of TCRV, and found that low-dose (10(4) 50% tissue culture infective dose [TCID(50)]) inoculations resulted in asymptomatic and apathogenic infection and virus clearance, while high-dose (10(6) TCID(50)) inoculations caused substantial morbidity and mortality as early as 10 days postinfection. Uninoculated cage mates failed to seroconvert, and viral RNA was not detected in their tissues, suggesting that transmission did not occur. Together, these data suggest that A. jamaicensis bats may not be a reservoir host for TCRV.",,"['Cogswell-Hawkinson, Ann', 'Bowen, Richard', 'James, Stephanie', 'Gardiner, David', 'Calisher, Charles H.', 'Adams, Rick', 'Schountz, Tony']",,,,
,PMC,"Isolation and Characterization of a Novel Betacoronavirus Subgroup A Coronavirus, Rabbit Coronavirus HKU14, from Domestic Rabbits",http://dx.doi.org/10.1128/JVI.06927-11,PMC3347282,,,"We describe the isolation and characterization of a novel Betacoronavirus subgroup A coronavirus, rabbit coronavirus HKU14 (RbCoV HKU14), from domestic rabbits. The virus was detected in 11 (8.1%) of 136 rabbit fecal samples by reverse transcriptase PCR (RT-PCR), with a viral load of up to 10(8) copies/ml. RbCoV HKU14 was able to replicate in HRT-18G and RK13 cells with cytopathic effects. Northern blotting confirmed the production of subgenomic mRNAs coding for the HE, S, NS5a, E, M, and N proteins. Subgenomic mRNA analysis revealed a transcription regulatory sequence, 5′-UCUAAAC-3′. Phylogenetic analysis showed that RbCoV HKU14 formed a distinct branch among Betacoronavirus subgroup A coronaviruses, being most closely related to but separate from the species Betacoronavirus 1. A comparison of the conserved replicase domains showed that RbCoV HKU14 possessed <90% amino acid identities to most members of Betacoronavirus 1 in ADP-ribose 1″-phosphatase (ADRP) and nidoviral uridylate-specific endoribonuclease (NendoU), indicating that RbCoV HKU14 should represent a separate species. RbCoV HKU14 also possessed genomic features distinct from those of other Betacoronavirus subgroup A coronaviruses, including a unique NS2a region with a variable number of small open reading frames (ORFs). Recombination analysis revealed possible recombination events during the evolution of RbCoV HKU14 and members of Betacoronavirus 1, which may have occurred during cross-species transmission. Molecular clock analysis using RNA-dependent RNA polymerase (RdRp) genes dated the most recent common ancestor of RbCoV HKU14 to around 2002, suggesting that this virus has emerged relatively recently. Antibody against RbCoV was detected in 20 (67%) of 30 rabbit sera tested by an N-protein-based Western blot assay, whereas neutralizing antibody was detected in 1 of these 20 rabbits.",,"['Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Yip, Cyril C. Y.', 'Fan, Rachel Y. Y.', 'Huang, Yi', 'Wang, Ming', 'Guo, Rongtong', 'Lam, Carol S. F.', 'Tsang, Alan K. L.', 'Lai, Kenneth K. Y.', 'Chan, Kwok-Hung', 'Che, Xiao-Yan', 'Zheng, Bo-Jian', 'Yuen, Kwok-Yung']",,,,
,PMC,Visualizing Coronavirus RNA Synthesis in Time by Using Click Chemistry,http://dx.doi.org/10.1128/JVI.07207-11,PMC3347275,,,"Coronaviruses induce in infected cells the formation of replicative structures, consisting of double-membrane vesicles (DMVs) and convoluted membranes, where viral RNA synthesis supposedly takes place and to which the nonstructural proteins (nsp's) localize. Double-stranded RNA (dsRNA), the presumed intermediate in RNA synthesis, is localized to the DMV interior. However, as pores connecting the DMV interior with the cytoplasm have not been detected, it is unclear whether RNA synthesis occurs at these same sites. Here, we studied coronavirus RNA synthesis by feeding cells with a uridine analogue, after which nascent RNAs were detected using click chemistry. Early in infection, nascent viral RNA and nsp's colocalized with or occurred adjacent to dsRNA foci. Late in infection, the correlation between dsRNA dots, then found dispersed throughout the cytoplasm, and nsp's and nascent RNAs was less obvious. However, foci of nascent RNAs were always found to colocalize with the nsp12-encoded RNA-dependent RNA polymerase. These results demonstrate the feasibility of detecting viral RNA synthesis by using click chemistry and indicate that dsRNA dots do not necessarily correspond with sites of active viral RNA synthesis. Rather, late in infection many DMVs may harbor dsRNA molecules that are no longer functioning as intermediates in RNA synthesis.",,"['Hagemeijer, Marne C.', 'Vonk, Annelotte M.', 'Monastyrska, Iryna', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.']",,,,
,PMC,"Clinical Features and Outcome of 65 Laboratory Confirmed Cases of H1N1 in Muscat, Sultanate of Oman",http://dx.doi.org/10.5001/omj.2012.46,PMC3394368,,,"OBJECTIVES: Responding to Pandemic Influenza A (H1N1) virus alert in 2009, Ministry of Health (MoH), Sultanate Of Oman arranged task force to deal with the emergency. MOH published articles in newspapers, prepared guidelines and hospitals were assigned to admit patients of H1N1. All the patients suspected of H1N1 were admitted and isolated as per the guidelines. This report describes clinical features and outcomes of 65 laboratory confirmed cases of H1N1 in Muscat, Sultanate of Oman. METHODS: From July to October 2009, 101 cases suspected of suffering from Pandemic Influenza A (H1N1) virus were admitted and isolated in Al Nahdha Hospital in Muscat. All the patients on admission were tested for H1N1, by real time reverse transcriptase polymerase chain reaction (RT-PCR). Immediately on admission, all of them were treated with Oseltamivir and antibiotics. RESULTS: Of the 65 confirmed cases of H1N1, 53.84% were males. Age of patients varied from 14 to 60 years, while 53.7% were aged between 31 to 55 years. Results showed that 70.8% had underlying co-morbidity; among which diabetes mellitus and respiratory illness were common. The most common presenting symptoms were fever (95%) and cough (94%). Also, 20% of the patients had leucopenia and 10.8% leucocytosis. Deranged LFT was observed in 26 (42.6%) of cases while 14 (21.5%) had hypokalemia. One patient (0.01%) with underlying severe co-morbidity died. Two patients (3.1%) had ARDS (Acute Respiratory Distress Syndrome); both recovered. Radiological infiltration was documented in 84.6% of cases, with lower zone involvement as the common finding. Hospital stay was between 1 to 12 days, 49.2% of patients were discharged within 3 days. CONCLUSION: Mainly adult population was affected during this epidemic. H1N1 infection can lead to severe illness. Incidence of H1N1 was higher in patients with underlying co-morbidity. Timely intervention and administration of Oseltamivir may need to be modified.",,"['Pajankar, Sumant', 'Al Qassabi, Salim Said', 'Al Harthi, Saud Mohamed']",,,,
,PMC,From SARS to 2009 H1N1 Influenza: The Evolution of a Public Health Incident Management System at CDC,,PMC3314070,,,"The organization of the response to infectious disease outbreaks by public health agencies at the federal, state, and local levels has historically been based on traditional public health functions (e.g., epidemiology, surveillance, laboratory, infection control, and health communications). Federal guidance has established a framework for the management of domestic incidents, including public health emergencies. Therefore, public health agencies have had to find a way to incorporate traditional public health functions into the common response framework of the National Incident Management System. One solution is the development of a Science Section, containing public health functions, that is equivalent to the traditional incident command system sections. Public health agencies experiencing difficulties in developing incident management systems should consider the feasibility and suitability of creating a Science Section to allow a more seamless and effective coordination of a public health response, while remaining consistent with current federal guidance.",,"['Papagiotas, Stephen S.', 'Frank, Mark', 'Bruce, Sherrie', 'Posid, Joseph M.']",,,,
,PMC,Loss of Mammal-specific Tectorial Membrane Component Carcinoembryonic Antigen Cell Adhesion Molecule 16 (CEACAM16) Leads to Hearing Impairment at Low and High Frequencies,http://dx.doi.org/10.1074/jbc.M111.320481,PMC3381124,,,"The vertebrate-restricted carcinoembryonic antigen gene family evolves extremely rapidly. Among their widely expressed members, the mammal-specific, secreted CEACAM16 is exceptionally well conserved and specifically expressed in the inner ear. To elucidate a potential auditory function, we inactivated murine Ceacam16 by homologous recombination. In young Ceacam16(−/−) mice the hearing threshold for frequencies below 10 kHz and above 22 kHz was raised. This hearing impairment progressed with age. A similar phenotype is observed in hearing-impaired members of Family 1070 with non-syndromic autosomal dominant hearing loss (DFNA4) who carry a missense mutation in CEACAM16. CEACAM16 was found in interdental and Deiters cells and was deposited in the tectorial membrane of the cochlea between postnatal days 12 and 15, when hearing starts in mice. In cochlear sections of Ceacam16(−/−) mice tectorial membranes were significantly more often stretched out as compared with wild-type mice where they were mostly contracted and detached from the outer hair cells. Homotypic cell sorting observed after ectopic cell surface expression of the carboxyl-terminal immunoglobulin variable-like N2 domain of CEACAM16 indicated that CEACAM16 can interact in trans. Furthermore, Western blot analyses of CEACAM16 under reducing and non-reducing conditions demonstrated oligomerization via unpaired cysteines. Taken together, CEACAM16 can probably form higher order structures with other tectorial membrane proteins such as α-tectorin and β-tectorin and influences the physical properties of the tectorial membrane. Evolution of CEACAM16 might have been an important step for the specialization of the mammalian cochlea, allowing hearing over an extended frequency range.",,"['Kammerer, Robert', 'Rüttiger, Lukas', 'Riesenberg, Rainer', 'Schäuble, Constanze', 'Krupar, Rosemarie', 'Kamp, Annegret', 'Sunami, Kishiko', 'Eisenried, Andreas', 'Hennenberg, Martin', 'Grunert, Fritz', 'Bress, Andreas', 'Battaglia, Sebastiano', 'Schrewe, Heinrich', 'Knipper, Marlies', 'Schneider, Marlon R.', 'Zimmermann, Wolfgang']",,,,
,PMC,CD13 Regulates Dendritic Cell Cross-presentation and T Cell Responses by Inhibiting Receptor-Mediated Antigen Uptake,http://dx.doi.org/10.4049/jimmunol.1103490,PMC3358354,,,"Dendritic cell (DC) antigen cross-presentation is generally associated with immune responses to tumors and viral antigens and enhancing this process is a focus of tumor vaccine design. In this study, we found that the myeloid cell surface peptidase CD13 is highly and specifically expressed on the subset of DCs responsible for cross-presentation, the CD8(+) murine splenic DCs. In vivo studies indicated that lack of CD13 significantly enhanced T cell responses to soluble OVA antigen, although development, maturation, antigen processing and presentation of DCs are normal in CD13KO mice. In vitro studies showed that CD13 regulates receptor-mediated, dynamin-dependent endocytosis of antigens such as OVA and transferrin but not fluid-phase or phagocytic antigen uptake. CD13 and antigen are co-internalized in DCs but CD13 did not co-immunoprecipitate with antigen receptors, suggesting that CD13 does not control internalization of specific receptors but regulates endocytosis at a more universal level. Mechanistically, we found that phosphorylation of the endocytic regulators p38MAPK and Akt was dysregulated in CD13KO DCs and blocking these kinases perturbed CD13-dependent endocytic uptake. Therefore, CD13 is a novel endocytic regulator that may be exploited to enhance antigen uptake and T cell activation to improve the efficacy of tumor-targeted vaccines.",,"['Ghosh, Mallika', 'McAuliffe, Beata', 'Subramani, Jaganathan', 'Basu, Sreyashi', 'Shapiro, Linda H']",,,,
,PMC,Interferon-inducible effector mechanisms in cell-autonomous immunity,http://dx.doi.org/10.1038/nri3210,PMC4150610,,,"Interferons (IFNs) induce the expression of hundreds of genes as part of an elaborate antimicrobial programme designed to combat infection in all nucleated cells — a process termed cell-autonomous immunity. As described in this Review, recent genomic and subgenomic analyses have begun to assign functional properties to novel IFN-inducible effector proteins that restrict bacteria, protozoa and viruses in different subcellular compartments and at different stages of the pathogen life cycle. Several newly described host defence factors also participate in canonical oxidative and autophagic pathways by spatially coordinating their activities to enhance microbial killing. Together, these IFN-induced effector networks help to confer vertebrate host resistance to a vast and complex microbial world.",,"MacMicking, John D.",,,,
,PMC,Avian influenza rapidly induces antiviral genes in duck lung and intestine,http://dx.doi.org/10.1016/j.molimm.2012.03.034,PMC3358531,,,"Ducks are the natural reservoir of influenza A and survive infection by most strains. To characterize the duck immune response to influenza, we sought to identify innate immune genes expressed early in an infection. We used suppressive subtractive hybridization (SSH) to construct 3 libraries enriched in differentially expressed genes from lung RNA of a duck infected with highly pathogenic avian influenza virus A/Vietnam/1203/04 (H5N1), or lung and intestine RNA of a duck infected with low pathogenic avian influenza A/mallard/BC/500/05 (H5N2) compared to a mock-infected duck. Sequencing of 1687 clones identified a transcription profile enriched in genes involved in antiviral defense and other cellular processes. Major histocompatibility complex class I (MHC I), interferon induced protein with tricopeptide repeats 5 (IFIT5), and 2′–5′oligoadenylate synthetase-like gene (OASL) were increased more than 1000-fold in relative transcript abundance in duck lung at 1 dpi with highly pathogenic VN1203. These genes were induced much less in lung or intestine following infection with low pathogenic BC500. The expression of these genes following infection suggests that ducks initiate an immediate and robust response to a potentially lethal influenza strain, and a minimal response a low pathogenic strain.",,"['Vanderven, Hillary A.', 'Petkau, Kristina', 'Ryan-Jean, Kieran E. E.', 'Aldridge, Jerry R.', 'Webster, Robert G.', 'Magor, Katharine E.']",,,,
,PMC,Emerging View of the Human Virome,http://dx.doi.org/10.1016/j.trsl.2012.03.006,PMC3701101,,,"The human virome is the collection of all viruses that are found in or on humans, including both eukaryotic and prokaryotic viruses. Eukaryotic viruses clearly have important effects on human health, ranging from mild, self-limited acute or chronic infections to those with serious or fatal consequences. Prokaryotic viruses can also affect human health by impacting bacterial community structure and function. Therefore, definition of the virome is an important step toward understanding how microbes affect human health and disease. We review progress in virome analysis, which has been driven by advances in high-throughput, deep sequencing technology. Highlights from these studies include the association of viruses with clinical phenotypes and description of novel viruses that may be important pathogens. Together these studies indicate that analysis of the human virome is critical as we aim to understand how microbial communities affect human health and disease. Descriptions of the human virome will stimulate future work to understand how the virome affects long-term human health, immunity, and response to co-infections. Ultimately analysis of the virome may affect the treatment of patients with a variety of clinical syndromes.",,"['Wylie, Kristine M.', 'Weinstock, George M.', 'Storch, Gregory A.']",,,,
,PMC,Critical paths in a metapopulation model of H1N1: Efficiently delaying influenza spreading through flight cancellation,http://dx.doi.org/10.1371/4f8c9a2e1fca8,PMC3392097,22919563,CC BY,"Disease spreading through human travel networks has been a topic of great interest in recent years, as witnessed during outbreaks of influenza A (H1N1) or SARS pandemics. One way to stop spreading over the airline network are travel restrictions for major airports or network hubs based on the total number of passengers of an airport. Here, we test alternative strategies using edge removal, cancelling targeted flight connections rather than restricting traffic for network hubs, for controlling spreading over the airline network. We employ a SEIR metapopulation model that takes into account the population of cities, simulates infection within cities and across the network of the top 500 airports, and tests different flight cancellation methods for limiting the course of infection. The time required to spread an infection globally, as simulated by a stochastic global spreading model was used to rank the candidate control strategies. The model includes both local spreading dynamics at the level of populations and long-range connectivity obtained from real global airline travel data. Simulated spreading in this network showed that spreading infected 37% less individuals after cancelling a quarter of flight connections between cities, as selected by betweenness centrality. The alternative strategy of closing down whole airports causing the same number of cancelled connections only reduced infections by 18%. In conclusion, selecting highly ranked single connections between cities for cancellation was more effective, resulting in fewer individuals infected with influenza, compared to shutting down whole airports. It is also a more efficient strategy, affecting fewer passengers while producing the same reduction in infections.",2012 Apr 23,"['Marcelino, Jose', 'Kaiser, Marcus']",PLoS Curr,,,
,PMC,Non-degradative Role of Atg5-Atg12/Atg16L1 Autophagy Protein Complex in Antiviral Activity of Interferon gamma,http://dx.doi.org/10.1016/j.chom.2012.03.002,PMC3348177,,,"Host resistance to viral infection requires Type-I (α/β) and -II (γ) interferon (IFN) production. Another important defense mechanism is the degradative activity of macroautophagy (herein autophagy), mediated by the coordinated action of evolutionarily conserved autophagy proteins (Atg). We show that the Atg5-Atg12/Atg16L1 protein complex, whose prior known function is in autophagosome formation, is required for IFNγ-mediated host defense against murine norovirus (MNV) infection. Importantly, the direct antiviral activity of IFNγ against MNV in macrophages required Atg5-Atg12, Atg7, and Atg16L1, but not induction of autophagy, the degradative activity of lysosomal proteases, fusion of autophagosomes and lysosomes, or the Atg8 processing protein Atg4B. IFNγ, via Atg5-Atg12/Atg16L1, inhibited formation of the membranous cytoplasmic MNV replication complex, where Atg16L1 localized. Thus, the Atg5-Atg12/Atg16L1 complex performs a pivotal, nondegradative role in IFNγ-mediated antiviral defense, establishing that multicellular organisms have evolved to use portions of the autophagy pathway machinery in a cassette-like fashion for host defense.",,"['Hwang, Seungmin', 'Maloney, Nicole S.', 'Bruinsma, Monique W.', 'Goel, Gautam', 'Duan, Erning', 'Zhang, Lei', 'Shrestha, Bimmi', 'Diamond, Michael S.', 'Dani, Adish', 'Sosnovtsev, Stanislav V.', 'Green, Kim Y.', 'Lopez-Otin, Carlos', 'Xavier, Ramnik J.', 'Thackray, Larissa B.', 'Virgin, Herbert W.']",,,,
,PMC,Synthesis and Biochemical Evaluation of Thiochromanone Thiosemicarbazone Analogues as Inhibitors of Cathepsin L,http://dx.doi.org/10.1021/ml200299g,PMC4025852,,,"[Image: see text] A series of 36 thiosemicarbazone analogues containing the thiochromanone molecular scaffold functionalized primarily at the C-6 position were prepared by chemical synthesis and evaluated as inhibitors of cathepsins L and B. The most promising inhibitors from this group are selective for cathepsin L and demonstrate IC(50) values in the low nanomolar range. In nearly all cases, the thiochromanone sulfide analogues show superior inhibition of cathepsin L as compared to their corresponding thiochromanone sulfone derivatives. Without exception, the compounds evaluated were inactive (IC(50) > 10000 nM) against cathepsin B. The most potent inhibitor (IC(50) = 46 nM) of cathepsin L proved to be the 6,7-difluoro analogue 4. This small library of compounds significantly expands the structure–activity relationship known for small molecule, nonpeptidic inhibitors of cathepsin L.",,"['Song, Jiangli', 'Jones, Lindsay\nM.', 'Kumar, G. D. Kishore', 'Conner, Elizabeth S.', 'Bayeh, Liela', 'Chavarria, Gustavo E.', 'Charlton-Sevcik, Amanda K.', 'Chen, Shen-En', 'Chaplin, David J.', 'Trawick, Mary Lynn', 'Pinney, Kevin G.']",,,,
,PMC,Prediction of invasion from the early stage of an epidemic,http://dx.doi.org/10.1098/rsif.2012.0130,PMC3405761,,,"Predictability of undesired events is a question of great interest in many scientific disciplines including seismology, economy and epidemiology. Here, we focus on the predictability of invasion of a broad class of epidemics caused by diseases that lead to permanent immunity of infected hosts after recovery or death. We approach the problem from the perspective of the science of complexity by proposing and testing several strategies for the estimation of important characteristics of epidemics, such as the probability of invasion. Our results suggest that parsimonious approximate methodologies may lead to the most reliable and robust predictions. The proposed methodologies are first applied to analysis of experimentally observed epidemics: invasion of the fungal plant pathogen Rhizoctonia solani in replicated host microcosms. We then consider numerical experiments of the susceptible–infected–removed model to investigate the performance of the proposed methods in further detail. The suggested framework can be used as a valuable tool for quick assessment of epidemic threat at the stage when epidemics only start developing. Moreover, our work amplifies the significance of the small-scale and finite-time microcosm realizations of epidemics revealing their predictive power.",,"['Pérez-Reche, Francisco J.', 'Neri, Franco M.', 'Taraskin, Sergei N.', 'Gilligan, Christopher A.']",,,,
,PMC,Polymer nanoparticle-mediated delivery of microRNA inhibition and alternative splicing,http://dx.doi.org/10.1021/mp300081s,PMC3366258,,,"The crux of current RNA-based therapeutics relies on association of synthetic nucleic acids with cellular RNA targets. Antisense oligonucleotide binding to mature microRNA and splicing junctions on pre-mRNA represent methods of gene therapy that respectively inhibit microRNA-mediated gene regulation and induce alternative splicing. We have developed biodegradable polymer nanoparticles--which are coated with cell-penetrating peptides--that can effectively deliver chemically-modified oligonucleotide analogs to achieve these forms of gene regulation. We found that this nanoparticle system could block the activity of the oncogenic microRNA, miR-155, as well as modulate splicing to attenuate the expression of the proto-oncogene, MCL-1. Regulation of these genes in human cancer cells reduced cell viability and produced pro-apoptotic effects. These findings establish polymer nanoparticles as delivery vectors for non-conventional forms of gene therapy activated by cellular delivery of RNA-targeted molecules, which have strong therapeutic implications.",,"['Cheng, Christopher J.', 'Saltzman, W. Mark']",,,,
,PMC,Expansion of polyreactive B cells cross-reactive to HLA and self in the blood of a patient with kidney graft rejection,http://dx.doi.org/10.1111/j.1600-6143.2012.04053.x,PMC3402627,,,"Antibody rejection is often accompanied by non-donor HLA specific antibodies (NDSA) and self-reactive antibodies that develop alongside donor-specific antibodies (DSA). To determine the source of these antibodies, we immortalized 107 B cell clones from a kidney transplant recipient with humoral rejection. Two of these clones reacted to HLA class I or MICA. Both clones were also reactive to self antigens and a lysate of a kidney cell line, hence revealing a pattern of polyreactivity. Monoclonality was verified by the identification of a single rearranged immunoglobulin heavy chain variable region (VH) sequence for each clone. By tracking their unique CDR3 sequence, we found that one such polyreactive clone was highly expanded in the patient blood, representing ~0.2% of circulating B cells. The VH sequence of this clone showed evidence of somatic mutations that were consistent with its memory phenotype and its expansion. Lastly, the reactivity of the expanded polyreactive B cell clone was found in the patient serum at time of rejection. In conclusion, we provide here proof of principle at the clonal level that human antibodies can cross-react to HLA and self. Our findings strongly suggest that polyreactive antibodies contribute to DSA, NDSA as well as autoantibodies, in transplant recipients.",,"['Porcheray, Fabrice', 'DeVito, Julie', 'Helou, Ynes', 'Dargon, Ian', 'Fraser, James W.', 'Nobecourt, Priscilla', 'Ferdman, Jack', 'Germana, Sharon', 'Girouard, Timothy C.', 'Kawai, Tatsuo', 'Saidman, Susan L.', 'Wong, Waichi', 'Colvin, Robert B.', 'Leguern, Christian', 'Zorn, Emmanuel']",,,,
,PMC,S-Palmitoylation and Ubiquitination Differentially Regulate Interferon-induced Transmembrane Protein 3 (IFITM3)-mediated Resistance to Influenza Virus,http://dx.doi.org/10.1074/jbc.M112.362095,PMC3365998,,,"The interferon (IFN)-induced transmembrane protein 3 (IFITM3) is a cellular restriction factor that inhibits infection by influenza virus and many other pathogenic viruses. IFITM3 prevents endocytosed virus particles from accessing the host cytoplasm although little is known regarding its regulatory mechanisms. Here we demonstrate that IFITM3 localization to and antiviral remodeling of endolysosomes is differentially regulated by S-palmitoylation and lysine ubiquitination. Although S-palmitoylation enhances IFITM3 membrane affinity and antiviral activity, ubiquitination decreases localization with endolysosomes and decreases antiviral activity. Interestingly, autophagy reportedly induced by IFITM3 expression is also negatively regulated by ubiquitination. However, the canonical ATG5-dependent autophagy pathway is not required for IFITM3 activity, indicating that virus trafficking from endolysosomes to autophagosomes is not a prerequisite for influenza virus restriction. Our characterization of IFITM3 ubiquitination sites also challenges the dual-pass membrane topology predicted for this protein family. We thus evaluated topology by N-linked glycosylation site insertion and protein lipidation mapping in conjunction with cellular fractionation and fluorescence imaging. Based on these studies, we propose that IFITM3 is predominantly an intramembrane protein where both the N and C termini face the cytoplasm. In sum, by characterizing S-palmitoylation and ubiquitination of IFITM3, we have gained a better understanding of the trafficking, activity, and intramembrane topology of this important IFN-induced effector protein.",,"['Yount, Jacob S.', 'Karssemeijer, Roos A.', 'Hang, Howard C.']",,,,
,PMC,Discovery of Critical Residues for Viral Entry and Inhibition through Structural Insight of HIV-1 Fusion Inhibitor CP621–652,http://dx.doi.org/10.1074/jbc.M112.354126,PMC3370210,,,"The core structure of HIV-1 gp41 is a stable six-helix bundle (6-HB) folded by its trimeric N- and C-terminal heptad repeats (NHR and CHR). We previously identified that the (621)QIWNNMT(627) motif located at the upstream region of gp41 CHR plays critical roles for the stabilization of the 6-HB core and peptide CP621–652 containing this motif is a potent HIV-1 fusion inhibitor, however, the molecular determinants underlying the stability and anti-HIV activity remained elusive. In this study, we determined the high-resolution crystal structure of CP621–652 complexed by T21. We find that the (621)QIWNNMT(627) motif does not maintain the α-helical conformation. Instead, residues Met(626) and Thr(627) form a unique hook-like structure (denoted as M-T hook), in which Thr(627) redirects the peptide chain to position Met(626) above the left side of the hydrophobic pocket on the NHR trimer. The side chain of Met(626) caps the hydrophobic pocket, stabilizing the interaction between the pocket and the pocket-binding domain. Our mutagenesis studies demonstrate that mutations of the M-T hook residues could completely abolish HIV-1 Env-mediated cell fusion and virus entry, and significantly destabilize the interaction of NHR and CHR peptides and reduce the anti-HIV activity of CP621–652. Our results identify an unusual structural feature that stabilizes the six-helix bundle, providing novel insights into the mechanisms of HIV-1 fusion and inhibition.",,"['Chong, Huihui', 'Yao, Xue', 'Qiu, Zonglin', 'Qin, Bo', 'Han, Ruiyun', 'Waltersperger, Sandro', 'Wang, Meitian', 'Cui, Sheng', 'He, Yuxian']",,,,
,PMC,Characterization of a novel splice variant of δ ENaC subunit in human lungs,http://dx.doi.org/10.1152/ajplung.00331.2011,PMC3379047,,,"Salt absorption via apical epithelial sodium channels (ENaC) is a critical rate-limiting process in maintaining airway and lung lining fluid at the physiological level. δ ENaC (termed δ1 in this article) has been detected in human lung epithelial cells in addition to α, β, and γ subunits (Ji HL, Su XF, Kedar S, Li J, Barbry P, Smith PR, Matalon S, Benos DJ. J Biol Chem 281: 8233–8241, 2006; Nie HG, Chen L, Han DY, Li J, Song WF, Wei SP, Fang XH, Gu X, Matalon S, Ji HL, J Physiol 587: 2663–2676, 2009) and may contribute to the differences in the biophysical properties of amiloride-inhibitable cation channels in pulmonary epithelial cells. Here we cloned a splicing variant of the δ1 ENaC, namely, δ2 ENaC in human bronchoalveolar epithelial cells (16HBEo). δ2 ENaC possesses 66 extra amino acids attached to the distal amino terminal tail of the δ1 ENaC. δ2 ENaC was expressed in both alveolar type I and II cells of human lungs as revealed by in situ hybridization and real-time RT-PCR. To characterize the biophysical and pharmacological features of the splicing variant, we injected Xenopus oocytes with human ENaC cRNAs and measured whole cell and single channel currents of δ1βγ, δ2βγ, and αβγ channels. Oocytes injected with δ2βγ cRNAs exhibited whole cell currents significantly greater than those expressing δ1βγ and αβγ channels. Single channel activity, unitary conductance, and open probability of δ2βγ channels were significantly greater compared with δ1βγ and αβγ channels. In addition, δ2βγ and δ1βγ channels displayed significant differences in apparent Na(+) affinity, dissociation constant for amiloride (K(i)(amil)), the EC(50) for capsazepine activation, and gating kinetics by protons. Channels comprising of this novel splice variant may contribute to the diversities of native epithelial Na(+) channels.",,"['Zhao, Run-Zhen', 'Nie, Hong-Guang', 'Su, Xue-Feng', 'Han, Dong-Yun', 'Lee, Andrew', 'Huang, Yao', 'Chang, Yongchang', 'Matalon, Sadis', 'Ji, Hong-Long']",,,,
,PMC,Loss of DRAK2 signaling enhances allogeneic transplant survival by limiting effector and memory T cell responses*,http://dx.doi.org/10.1111/j.1600-6143.2012.04056.x,PMC3396732,,,"Here we demonstrate that loss of DRAK2 signaling significantly promotes the acceptance of allogeneic engraftment in two separate transplant models without promoting generalized immunosuppression. Drak2-/- T cells failed to reject allogeneic tumors, and were defective in rejecting Balb/C allogeneic skin grafts on C57BL6/J recipients. A significant fraction of alloreactive Drak2-/- T cells underwent apoptosis following activation, whereas enforced expression of Bcl-xL in Drak2-/- T cells restored allograft rejection. Formation of allogeneic memory was also greatly hampered in T cells lacking the Drak2 gene. Adoptive transfer of memory T cells from Drak2-/- mice failed to promote the rejection of allogeneic tumors, and such cells led to significantly delayed rejection of skin allografts in the Balb/C->C57BL/6J model. Costimulatory blockade by in vivo administration of Cytotoxic T-Lymphocyte Antigen 4 fusion protein (CTLA4-Ig) synergized with the DRAK2 deficiency and led to long-term allogeneic skin graft acceptance. Overall, these results demonstrate that DRAK2 plays an important role in primary and memory T cell responsiveness to allografts. Since previous studies have demonstrated that a loss of DRAK2 does not negatively impact antiviral immunity, the studies here underscore the potential utility of pharmacological blockade of DRAK2 to achieve transplant maintenance without the imposition of generalized immunosuppression.",,"['Weist, Brian M.', 'Hernandez, Jeniffer B.', 'Walsh, Craig M.']",,,,
,PMC,Statistical mechanical modeling of RNA folding: from free energy landscape to tertiary structural prediction,http://dx.doi.org/10.1007/978-3-642-25740-7_10,PMC4902161,,,"In spite of the success of computational methods for predicting RNA secondary structure, the problem of predicting RNA tertiary structure folding remains. Low-resolution structural models show promise as they allow for rigorous statistical mechanical computation for the conformational entropies, free energies, and the coarse-grained structures of tertiary folds. Molecular dynamics refinement of coarse-grained structures leads to all-atom 3D structures. Modeling based on statistical mechanics principles also has the unique advantage of predicting the full free energy landscape, including local minima and the global free energy minimum. The energy landscapes combined with the 3D structures form the basis for quantitative predictions of RNA functions. In this chapter, we present an overview of statistical mechanical models for RNA folding and then focus on a recently developed RNA statistical mechanical model -- the Vfold model. The main emphasis is placed on the physics underpinning the models, the computational strategies, and the connections to RNA biology.",,"['CAO, Song', 'CHEN, Shi-Jie']",,,,
,PMC,Immunosuppression Decreases Inflammation and Increases AAV6-hSERCA2a-Mediated SERCA2a Expression,http://dx.doi.org/10.1089/hum.2011.108,PMC3404422,,,"The calcium pump SERCA2a (sarcoplasmic reticulum calcium ATPase 2a), which plays a central role in cardiac contraction, shows decreased expression in heart failure (HF). Increasing SERCA2a expression in HF models improves cardiac function. We used direct cardiac delivery of adeno-associated virus encoding human SERCA2a (AAV6-hSERCA2a) in HF and normal canine models to study safety, efficacy, and the effects of immunosuppression. Tachycardic-paced dogs received left ventricle (LV) wall injection of AAV6-hSERCA2a or solvent. Pacing continued postinjection for 2 or 6 weeks, until euthanasia. Tissue/serum samples were analyzed for hSERCA2a expression (Western blot) and immune responses (histology and AAV6-neutralizing antibodies). Nonpaced dogs received AAV6-hSERCA2a and were analyzed at 12 weeks; a parallel cohort received AAV-hSERCA2a and immunosuppression. AAV-mediated cardiac expression of hSERCA2a peaked at 2 weeks and then declined (to ∼50%; p<0.03, 6 vs. 2 weeks). LV end diastolic and end systolic diameters decreased in 6-week dogs treated with AAV6-hSERCA2a (p<0.05) whereas LV diameters increased in control dogs. Dogs receiving AAV6-hSERCA2a developed neutralizing antibodies (titer ≥1:120) and cardiac cellular infiltration. Immunosuppression dramatically reduced immune responses (reduced inflammation and neutralizing antibody titers <1:20), and maintained hSERCA2a expression. Thus cardiac injection of AAV6-hSERCA2a promotes local hSERCA2a expression and improves cardiac function. However, the hSERCA2a protein level is reduced by host immune responses. Immunosuppression alleviates immune responses and sustains transgene expression, and may be an important adjuvant for clinical gene therapy trials.",,"['Zhu, Xiaodong', 'McTiernan, Charles F.', 'Rajagopalan, Navin', 'Shah, Hemal', 'Fischer, David', 'Toyoda, Yoshiya', 'Letts, Dustin', 'Bortinger, Jonathan', 'Gibson, Gregory', 'Xiang, Wenyu', 'McCurry, Kenneth', 'Mathier, Michael', 'Glorioso, Joseph C.', 'London, Barry']",,,,
,PMC,Targets and Intracellular Signaling Mechanisms for Deoxynivalenol-Induced Ribosomal RNA Cleavage,http://dx.doi.org/10.1093/toxsci/kfs134,PMC3355321,,,"The trichothecene mycotoxin deoxynivalenol (DON), a known translational inhibitor, induces ribosomal RNA (rRNA) cleavage. Here, we characterized this process relative to (1) specific 18S and 28S ribosomal RNA cleavage sites and (2) identity of specific upstream signaling elements in this pathway. Capillary electrophoresis indicated that DON at concentrations as low as 200 ng/ml evoked selective rRNA cleavage after 6 h and that 1000 ng/ml caused cleavage within 2 h. Northern blot analysis revealed that DON exposure induced six rRNA cleavage fragments from 28S rRNA and five fragments from 18S rRNA. When selective kinase inhibitors were used to identify potential upstream signals, RNA-activated protein kinase (PKR), hematopoietic cell kinase (Hck), and p38 were found to be required for rRNA cleavage, whereas c-Jun N-terminal kinase and extracellular signal-regulated kinase were not. Furthermore, rRNA fragmentation was suppressed by the p53 inhibitors pifithrin-α and pifithrin-μ as well as the pan caspase inhibitor Z-VAD-FMK. Concurrent apoptosis was confirmed by acridine orange/ethidium bromide staining and flow cytometry. DON activated caspases 3, 8, and 9, thus suggesting the possible coinvolvement of both extrinsic and intrinsic apoptotic pathways in rRNA cleavage. Satratoxin G (SG), anisomycin, and ricin also induced specific rRNA cleavage profiles identical to those of DON, suggesting that ribotoxins might share a conserved rRNA cleavage mechanism. Taken together, DON-induced rRNA cleavage is likely to be closely linked to apoptosis activation and appears to involve the sequential activation of PKR/Hck →p38→p53→caspase 8/9→caspase 3.",,"['He, Kaiyu', 'Zhou, Hui-Ren', 'Pestka, James J.']",,,,
,PMC,Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus,http://dx.doi.org/10.1073/pnas.1114927109,PMC3341081,,,"Hepatitis C virus (HCV) infects ∼2% of the world's population. It is estimated that there are more than 500,000 new infections annually in Egypt, the country with the highest HCV prevalence. An effective vaccine would help control this expanding global health burden. HCV is highly variable, and an effective vaccine should target conserved T- and B-cell epitopes of the virus. Conserved B-cell epitopes overlapping the CD81 receptor-binding site (CD81bs) on the E2 viral envelope glycoprotein have been reported previously and provide promising vaccine targets. In this study, we isolated 73 human mAbs recognizing five distinct antigenic regions on the virus envelope glycoprotein complex E1E2 from an HCV-immune phage-display antibody library by using an exhaustive-panning strategy. Many of these mAbs were broadly neutralizing. In particular, the mAb AR4A, recognizing a discontinuous epitope outside the CD81bs on the E1E2 complex, has an exceptionally broad neutralizing activity toward diverse HCV genotypes and protects against heterologous HCV challenge in a small animal model. The mAb panel will be useful for the design and development of vaccine candidates to elicit broadly neutralizing antibodies to HCV.",,"['Giang, Erick', 'Dorner, Marcus', 'Prentoe, Jannick C.', 'Dreux, Marlène', 'Evans, Matthew J.', 'Bukh, Jens', 'Rice, Charles M.', 'Ploss, Alexander', 'Burton, Dennis R.', 'Law, Mansun']",,,,
,PMC,Acute respiratory distress syndrome and lung injury: Pathogenetic mechanism and therapeutic implication,http://dx.doi.org/10.5492/wjccm.v1.i2.50,PMC3953859,,,"To review possible mechanisms and therapeutics for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). ALI/ARDS causes high mortality. The risk factors include head injury, intracranial disorders, sepsis, infections and others. Investigations have indicated the detrimental role of nitric oxide (NO) through the inducible NO synthase (iNOS). The possible therapeutic regimen includes extracorporeal membrane oxygenation, prone position, fluid and hemodynamic management and permissive hypercapnic acidosis etc. Other pharmacological treatments are anti-inflammatory and/or antimicrobial agents, inhalation of NO, glucocorticoids, surfactant therapy and agents facilitating lung water resolution and ion transports. β-adrenergic agonists are able to accelerate lung fluid and ion removal and to stimulate surfactant secretion. In conscious rats, regular exercise training alleviates the endotoxin-induced ALI. Propofol and N-acetylcysteine exert protective effect on the ALI induced by endotoxin. Insulin possesses anti-inflammatory effect. Pentobarbital is capable of reducing the endotoxin-induced ALI. In addition, nicotinamide or niacinamide abrogates the ALI caused by ischemia/reperfusion or endotoxemia. This review includes historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.",,"['Su, Chain-Fa', 'Kao, Shang Jyh', 'Chen, Hsing I']",,,,
,PMC,Progress in the Development of Hepatitis C Virus Vaccines,http://dx.doi.org/10.1038/mt.2012.30,PMC3321602,,,,,"Ertl, Hildegund CJ",,,,
,PMC,Catalytic Stereoselective Synthesis of Diverse Oxindoles and Spirooxindoles from Isatins,http://dx.doi.org/10.1021/co300003c,PMC4795923,,,"[Image: see text] A strategy for the efficient two-step synthesis of triazole derivatives of oxindoles and spirooxindoles is presented. Using a common set of N-propargylated isatins, a series of mechanistically-distinct stereoselective reactions with different combinations of nucleophiles and catalysts provide access to diverse hydroxy-oxindoles, spiroindolones, and spirocyclic oxazoline structures. The resulting N-propargylated oxindoles are then converted to triazoles using copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. Overall, this strategy affords a 64-member pilot-scale library of diverse oxindoles and spirooxindoles.",,"['MacDonald, Jacob P.', 'Badillo, Joseph J.', 'Arevalo, Gary E.', 'Silva-Garcia, Abel', 'K. Franz, Annaliese']",,,,
,PMC,The Anti-Inflammatory and Anti-Nociceptive Activities of Patrinia Villosa and Its Mechanism on the Proinflammatory Cytokines of Rats with Pelvic Inflammation,,PMC3746661,,,"This study explores the anti-inflammatory and anti-nociceptive activities of Patrinia villosa, a Chinese medicinal plant, and to explore its effects on the proinflammatory cytokines of the rats with pelvic inflammation model. The animals were randomly divided into Patrinia villosa group (PV group), dexamethasone group (DEX group), and model-control group (CON group) to perform an ear edema test, a carrageenin-induced paw edema test, a cotton pellet-induced granuloma formation test, and an acetic acid-induced writhing test. The model rats with pelvic inflammation were established, and the serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) in each group was detected with the Enzyme-Linked ImmunoSorbent Assay (ELISA). The results of the ear edema test, carrageenin-induced paw edema test, cotton pellet-induced granuloma formation test, and acetic acid-induced writhing test all showed that Patrinia villosa had strong anti-inflammatory and anti-nociceptive effects. In the experiment using model rats with pelvic inflammation, we found that the serum levels of IL-6, IL-8 and TNF-α in PV and DEX group were all significantly lower than those of the CON group, and the serum levels of IL-6 and IL-8 in PV group were significantly lower than those of the DEX group. Patrinia villosa, with its strong anti-inflammatory and anti-nociceptive activities, can be used to treat pelvic inflammation and to relieve the associated pain.",,"['Zheng, Yan', 'Jin, Yue', 'Zhu, Hai-Bin', 'Xu, Shao-Ting', 'Xia, Ya-Xian', 'Huang, Yue']",,,,
,PMC,The adaptive immune system in diseases of the central nervous system,http://dx.doi.org/10.1172/JCI58648,PMC3314451,,,"Tissues of the CNS, such as the brain, optic nerves, and spinal cord, may be affected by a range of insults including genetic, autoimmune, infectious, or neurodegenerative diseases and cancer. The immune system is involved in the pathogenesis of many of these, either by causing tissue damage or alternatively by responding to disease and contributing to repair. It is clearly vital that cells of the immune system patrol the CNS and protect against infection. However, in contrast to other tissues, damage caused by immune pathology in the CNS can be irreparable. The nervous and immune systems have, therefore, coevolved to permit effective immune surveillance while limiting immune pathology. Here we will consider aspects of adaptive immunity in the CNS and the retina, both in the context of protection from infection as well as cancer and autoimmunity, while focusing on immune responses that compromise health and lead to significant morbidity.",,"['Wraith, David C.', 'Nicholson, Lindsay B.']",,,,
,PMC,Innate immunity in the central nervous system,http://dx.doi.org/10.1172/JCI58644,PMC3314450,,,"Immune responses in the CNS are common, despite its perception as a site of immune privilege. These responses can be mediated by resident microglia and astrocytes, which are innate immune cells without direct counterparts in the periphery. Furthermore, CNS immune reactions often take place in virtual isolation from the innate/adaptive immune interplay that characterizes peripheral immunity. However, microglia and astrocytes also engage in significant cross-talk with CNS-infiltrating T cells and other components of the innate immune system. Here we review the cellular and molecular basis of innate immunity in the CNS and discuss what is known about how outcomes of these interactions can lead to resolution of infection, neurodegeneration, or neural repair depending on the context.",,"['Ransohoff, Richard M.', 'Brown, Melissa A.']",,,,
,PMC,Evaluation of a Monoclonal Antibody–Based Rapid Immunochromatographic Test for Direct Detection of Rabies Virus in the Brain of Humans and Animals,http://dx.doi.org/10.4269/ajtmh.2012.11-0332,PMC3403755,,,"Rabies diagnosis uses a direct fluorescent antibody test (FAT) that is difficult, costly, and time-consuming, and requires trained personnel. We developed a rapid immunochromatographic test (RICT) for the diagnosis of rabies. The efficacy of the RICT was compared with that of the FAT. Brain samples were collected from humans, dogs, cats, and other animals in Sri Lanka (n = 248), Bhutan (n = 27), and Thailand (n = 228). The sensitivity (0.74–0.95), specificity (0.98–1.0), positive predictive value (0.98–1.0), negative predictive value (0.75–0.97), accuracy (0.91–0.98), and kappa measure of agreement (0.79–0.93) were all satisfactory for animal samples and samples preserved in 50% glycerol saline solution. Because the RICT showed high sensitivity but low specificity with human brain samples, it is unsuitable for confirming rabies in humans. No amino acid substitutions were found in the antibody attachment sites of the nucleoprotein gene with FAT-positive, RICT-negative samples. The RICT is reliable, user friendly, rapid, robust, and can be used in laboratories with a modest infrastructure.",,"['Ahmed, Kamruddin', 'Wimalaratne, Omala', 'Dahal, Narapati', 'Khawplod, Pakamatz', 'Nanayakkara, Susilakanthi', 'Rinzin, Karma', 'Perera, Devika', 'Karunanayake, Dushantha', 'Matsumoto, Takashi', 'Nishizono, Akira']",,,,
,PMC,Multifarious roles of sialic acids in immunity,http://dx.doi.org/10.1111/j.1749-6632.2012.06517.x,PMC3357316,,,"Sialic acids are a diverse family of monosaccharides widely expressed on all cell surfaces of vertebrates and so-called “higher” invertebrates, and on certain bacteria that interact with vertebrates. This overview surveys examples of biological roles of sialic acids in immunity, with emphasis on an evolutionary perspective. Given the breadth of the subject, the treatment of individual topics is brief. Subjects discussed include biophysical effects regulation of factor H; modulation of leukocyte trafficking via selectins; Siglecs in immune cell activation; sialic acids as ligands for microbes; impact of microbial and endogenous sialidases on immune cell responses; pathogen molecular mimicry of host sialic acids; Siglec recognition of sialylated pathogens; bacteriophage recognition of microbial sialic acids; polysialic acid modulation of immune cells; sialic acids as pathogen decoys or biological masks; modulation of immunity by sialic acid O-acetylation, sialic acids as antigens and xeno-autoantigens; anti-sialoglycan antibodies in reproductive incompatibility, and sialic-acid based blood groups.",,"['Varki, Ajit', 'Gagneux, Pascal']",,,,
,PMC,Influenza at the beginning of the 21st century,http://dx.doi.org/10.2471/BLT.12.104653,PMC3324879,,,,,"['Shindo, Nahoko', 'Briand, Sylvie']",,,,
,PMC,"Developing pandemic preparedness in Europe in the 21st century: experience, evolution and next steps",http://dx.doi.org/10.2471/BLT.11.097972,PMC3324872,,,"PROBLEM: Improving pandemic planning and preparedness is a challenge in Europe, a diverse region whose regional bodies (the Regional Office for Europe of the World Health Organization [WHO], the European Commission and the European Centre for Disease Prevention and Control) have overlapping roles and responsibilities. APPROACH: European pandemic preparedness indicators were used to develop an assessment tool and procedure based on the 2005 global WHO checklist for pandemic preparedness. These were then applied to Member States of WHO’s European Region, initially as part of structured national assessments conducted during short visits by external teams. LOCAL SETTING: Countries in WHO’s European Region. RELEVANT CHANGES: From 2005 to 2008, 43 countries underwent a pandemic preparedness assessment that included a short external assessment visit by an expert team. These short visits developed into a longer self-assessment procedure involving an external team but “owned” by the countries, which identified gaps and developed plans for improving preparedness. The assessment tool and procedure became more sophisticated as national and local pandemic preparedness became more complex. The 2009 pandemic revealed new gaps in planning, surveillance communications and immunization. LESSONS LEARNT: Structured national self-assessments with support from external teams allow individual countries to identify gaps in their pandemic preparedness plans and enable regional bodies to assess the regional and global resources that such plans require. The 2009 pandemic revealed additional problems with surveillance, pandemic severity estimates, the flexibility of the response, vaccination, involvement of health-care workers and communication. European national plans are being upgraded and global leadership is required to ensure that these plans are uniformly applied across the region.",,"['Nicoll, Angus', 'Brown, Caroline', 'Karcher, Franz', 'Penttinen, Pasi', 'Hegermann-Lindencrone, Michala', 'Villanueva, Silvia', 'Ciotti, Massimo', 'Jean-Gilles, Lucie', 'Rehmet, Sybille', 'Nguyen-Van-Tam, Jonathan S']",,,,
,PMC,A Preliminary Study of Pneumonia Etiology Among Hospitalized Children in Kenya,http://dx.doi.org/10.1093/cid/cir1071,PMC3297554,,,"Background. Pneumonia is the leading cause of childhood death in the developing world. Higher-quality etiological data are required to reduce this mortality burden. Methods. We conducted a case-control study of pneumonia etiology among children aged 1–59 months in rural Kenya. Case patients were hospitalized with World Health Organization–defined severe pneumonia (SP) or very severe pneumonia (VSP); controls were outpatient children without pneumonia. We collected blood for culture, induced sputum for culture and multiplex polymerase chain reaction (PCR), and obtained oropharyngeal swab specimens for multiplex PCR from case patients, and serum for serology and nasopharyngeal swab specimens for multiplex PCR from case patients and controls. Results. Of 984 eligible case patients, 810 (84%) were enrolled in the study; 232 (29%) had VSP. Blood cultures were positive in 52 of 749 case patients (7%). A predominant potential pathogen was identified in sputum culture in 70 of 417 case patients (17%). A respiratory virus was detected by PCR from nasopharyngeal swab specimens in 486 of 805 case patients (60%) and 172 of 369 controls (47%). Only respiratory syncytial virus (RSV) showed a statistically significant association between virus detection in the nasopharynx and pneumonia hospitalization (odds ratio, 12.5; 95% confidence interval, 3.1–51.5). Among 257 case patients in whom all specimens (excluding serum specimens) were collected, bacteria were identified in 24 (9%), viruses in 137 (53%), mixed viral and bacterial infection in 39 (15%), and no pathogen in 57 (22%); bacterial causes outnumbered viral causes when the results of the case-control analysis were considered. Conclusions. A potential etiology was detected in >75% of children admitted with SP or VSP. Except for RSV, the case-control analysis did not detect an association between viral detection in the nasopharynx and hospitalization for pneumonia.",,"['Hammitt, Laura L.', 'Kazungu, Sidi', 'Morpeth, Susan C.', 'Gibson, Dustin G.', 'Mvera, Benedict', 'Brent, Andrew J.', 'Mwarumba, Salim', 'Onyango, Clayton O.', 'Bett, Anne', 'Akech, Donald O.', 'Murdoch, David R.', 'Nokes, D. James', 'Scott, J. Anthony G.']",,,,
,PMC,Use and Evaluation of Molecular Diagnostics for Pneumonia Etiology Studies,http://dx.doi.org/10.1093/cid/cir1060,PMC3297547,,,"Comprehensive microbiological testing will be a core function of the Pneumonia Etiology Research for Child Health (PERCH) project. The development stage of PERCH provided the time and resources necessary for us to conduct a comprehensive review of the current state of respiratory diagnostics. These efforts allowed us to articulate the unique requirements of PERCH, establish that molecular methods would be central to our testing strategy, and focus on a short list of candidate platforms. This process also highlighted critical challenges in the general design and interpretation of diagnostic evaluation studies, particularly in the field of respiratory infections. Although our final molecular diagnostic platform was ultimately selected on the basis of operational and strategic considerations determined by the specific context of PERCH, our review highlighted several conceptual and practical challenges in respiratory diagnostics that have broader relevance for the performance and interpretation of pneumonia research studies.",,"['Bhat, Niranjan', ""O'Brien, Katherine L."", 'Karron, Ruth A.', 'Driscoll, Amanda J.', 'Murdoch, David R.', None]",,,,
,PMC,Update on Influenza Diagnostics: Lessons from the Novel H1N1 Influenza A Pandemic,http://dx.doi.org/10.1128/CMR.05016-11,PMC3346302,,,"Summary: The menu of diagnostic tools that can be utilized to establish a diagnosis of influenza is extensive and includes classic virology techniques as well as new and emerging methods. This review of how the various existing diagnostic methods have been utilized, first in the context of a rapidly evolving outbreak of novel influenza virus and then during the different subsequent phases and waves of the pandemic, demonstrates the unique roles, advantages, and limitations of each of these methods. Rapid antigen tests were used extensively throughout the pandemic. Recognition of the low negative predictive values of these tests is important. Private laboratories with preexisting expertise, infrastructure, and resources for rapid development, validation, and implementation of laboratory-developed assays played an unprecedented role in helping to meet the diagnostic demands during the pandemic. FDA-cleared assays remain an important element of the diagnostic armamentarium during a pandemic, and a process must be developed with the FDA to allow manufacturers to modify these assays for detection of novel strains in a timely fashion. The need and role for subtyping of influenza viruses and antiviral susceptibility testing will likely depend on qualitative (circulating subtypes and their resistance patterns) and quantitative (relative prevalence) characterization of influenza viruses circulating during future epidemics and pandemics.",,"['Kumar, Swati', 'Henrickson, Kelly J.']",,,,
,PMC,Two Years after Pandemic Influenza A/2009/H1N1: What Have We Learned?,http://dx.doi.org/10.1128/CMR.05012-11,PMC3346300,,,"Summary: The world had been anticipating another influenza pandemic since the last one in 1968. The pandemic influenza A H1N1 2009 virus (A/2009/H1N1) finally arrived, causing the first pandemic influenza of the new millennium, which has affected over 214 countries and caused over 18,449 deaths. Because of the persistent threat from the A/H5N1 virus since 1997 and the outbreak of the severe acute respiratory syndrome (SARS) coronavirus in 2003, medical and scientific communities have been more prepared in mindset and infrastructure. This preparedness has allowed for rapid and effective research on the epidemiological, clinical, pathological, immunological, virological, and other basic scientific aspects of the disease, with impacts on its control. A PubMed search using the keywords “pandemic influenza virus H1N1 2009” yielded over 2,500 publications, which markedly exceeded the number published on previous pandemics. Only representative works with relevance to clinical microbiology and infectious diseases are reviewed in this article. A significant increase in the understanding of this virus and the disease within such a short amount of time has allowed for the timely development of diagnostic tests, treatments, and preventive measures. These findings could prove useful for future randomized controlled clinical trials and the epidemiological control of future pandemics.",,"['Cheng, Vincent C. C.', 'To, Kelvin K. W.', 'Tse, Herman', 'Hung, Ivan F. N.', 'Yuen, Kwok-Yung']",,,,
,PMC,The Presence of Alpha Interferon at the Time of Infection Alters the Innate and Adaptive Immune Responses to Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1128/CVI.05490-11,PMC3318278,,,"Porcine reproductive and respiratory syndrome (PRRS) is one of the most devastating and costly diseases to the swine industry worldwide. Overall, the adaptive immune response to PRRS virus (PRRSV) is weak, which results in delayed elimination of virus from the host and inferior vaccine protection. PRRSV has been shown to induce a meager alpha interferon (IFN-α) response, and we hypothesized that elevated IFN-α levels early in infection would shorten the induction time and increase elements of the adaptive immune response. To test this, we measured both antibody and cell-mediated immunity in pigs after the administration of a nonreplicating human adenovirus type 5 vector expressing porcine IFN-α (Ad5–pIFN-α) at the time of PRRSV infection and compared the results to those for pigs infected with PRRSV alone. Viremia was delayed, and there was a decrease in viral load in the sera of pigs administered the Ad5–pIFN-α. Although seroconversion was slightly delayed in pigs receiving Ad5–pIFN-α, probably due to the early reduction in viral replication, little difference in the overall or neutralizing antibody response was seen. However, there was an increase in the number of virus-specific IFN-γ-secreting cells detected in the pigs receiving Ad5–pIFN-α, as well as an altered cytokine profile in the lung at 14 days postinfection, indicating that the presence of IFN-α at the time of infection can alter innate and adaptive immune responses to PRRSV.",,"['Brockmeier, Susan L.', 'Loving, Crystal L.', 'Nelson, Eric A.', 'Miller, Laura C.', 'Nicholson, Tracy L.', 'Register, Karen B.', 'Grubman, Marvin J.', 'Brough, Douglas E.', 'Kehrli, Marcus E.']",,,,
,PMC,Emerging Therapeutics Targeting mRNA Translation,http://dx.doi.org/10.1101/cshperspect.a012377,PMC3312682,,,"A defining feature of many cancers is deregulated translational control. Typically, this occurs at the level of recruitment of the 40S ribosomes to the 5′-cap of cellular messenger RNAs (mRNAs), the rate-limiting step of protein synthesis, which is controlled by the heterotrimeric eukaryotic initiation complex eIF4F. Thus, eIF4F in particular, and translation initiation in general, represent an exploitable vulnerability and unique opportunity for therapeutic intervention in many transformed cells. In this article, we discuss the development, mode of action and biological activity of a number of small-molecule inhibitors that interrupt PI3K/mTOR signaling control of eIF4F assembly, as well as compounds that more directly block eIF4F activity.",,"['Malina, Abba', 'Mills, John R.', 'Pelletier, Jerry']",,,,
,PMC,A New Apparatus and Surgical Technique for the Dual Perfusion of Human Tumor Xenografts in Situ in Nude Rats,,PMC3318246,,,"We present a new perfusion system and surgical technique for simultaneous perfusion of 2 tissue-isolated human cancer xenografts in nude rats by using donor blood that preserves a continuous flow. Adult, athymic nude rats (Hsd:RH-Foxn1(rnu)) were implanted with HeLa human cervical or HT29 colon adenocarcinomas and grown as tissue-isolated xenografts. When tumors reached an estimated weight of 5 to 6 g, rats were prepared for perfusion with donor blood and arteriovenous measurements. The surgical procedure required approximately 20 min to complete for each tumor, and tumors were perfused for a period of 150 min. Results showed that tumor venous blood flow, glucose uptake, lactic acid release, O(2) uptake and CO(2) production, uptake of total fatty acid and linoleic acid and conversion to the mitogen 13-HODE, cAMP levels, and activation of several marker kinases were all well within the normal physiologic, metabolic, and signaling parameters characteristic of individually perfused xenografts. This new perfusion system and technique reduced procedure time by more than 50%. These findings demonstrate that 2 human tumors can be perfused simultaneously in situ or ex vivo by using either rodent or human blood and suggest that the system may also be adapted for use in the dual perfusion of other organs. Advantages of this dual perfusion technique include decreased anesthesia time, decreased surgical manipulation, and increased efficiency, thereby potentially reducing the numbers of laboratory animals required for scientific investigations.",,"['Dauchy, Robert T', 'Dauchy, Erin M', 'Mao, Lulu', 'Belancio, Victoria P', 'Hill, Steven M', 'Blask, David E']",,,,
,PMC,Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens,http://dx.doi.org/10.1096/fj.11-193466,PMC3316894,,,"Influenza virus encodes only 11 viral proteins but replicates in a broad range of avian and mammalian species by exploiting host cell functions. Genome-wide RNA interference (RNAi) has proven to be a powerful tool for identifying the host molecules that participate in each step of virus replication. Meta-analysis of findings from genome-wide RNAi screens has shown influenza virus to be dependent on functional nodes in host cell pathways, requiring a wide variety of molecules and cellular proteins for replication. Because rapid evolution of the influenza A viruses persistently complicates the effectiveness of vaccines and therapeutics, a further understanding of the complex host cell pathways coopted by influenza virus for replication may provide new targets and strategies for antiviral therapy. RNAi genome screening technologies together with bioinformatics can provide the ability to rapidly identify specific host factors involved in resistance and susceptibility to influenza virus, allowing for novel disease intervention strategies.—Meliopoulos, V. A., Andersen, L. E., Birrer, K. F., Simpson, K. J., Lowenthal, J. W., Bean, A. G. D., Stambas, J., Stewart, C. R., Tompkins, S. M., van Beusechem, V. W., Fraser, I., Mhlanga, M., Barichievy, S., Smith, Q., Leake, D., Karpilow, J., Buck, A., Jona, G., Tripp, R. A. Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens.",,"['Meliopoulos, Victoria A.', 'Andersen, Lauren E.', 'Birrer, Katherine F.', 'Simpson, Kaylene J.', 'Lowenthal, John W.', 'Bean, Andrew G. D.', 'Stambas, John', 'Stewart, Cameron R.', 'Tompkins, S. Mark', 'van Beusechem, Victor W.', 'Fraser, Iain', 'Mhlanga, Musa', 'Barichievy, Samantha', 'Smith, Queta', 'Leake, Devin', 'Karpilow, Jon', 'Buck, Amy', 'Jona, Ghil', 'Tripp, Ralph A.']",,,,
,PMC,CXCR2 signaling and host defense following coronavirus-induced encephalomyelitis,http://dx.doi.org/10.2217/fvl.12.23,PMC3348576,,,"Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of susceptible strains of mice results in wide-spread replication within glial cells accompanied by infiltration of virus-specific T lymphocytes that control virus through cytokine secretion and cytolytic activity. Virus persists within white matter tracts of surviving mice resulting in demyelination that is amplified by inflammatory T cells and macrophages. In response to infection, numerous cytokines/chemokines are secreted by resident cells of the CNS and inflammatory leukocytes that participate in both host defense and disease. Among these are the ELR-positive chemokines that are able to signal through CXC chemokine receptors including CXCR2. Early following JHMV infection, ELR-positive chemokines contribute to host defense by attracting CXCR2-expressing cells including polymorphonuclear cells to the CNS that aid in host defense through increasing the permeability the blood-brain-barrier (BBB). During chronic disease, CXCR2 signaling on oligodendroglia protects these cells from apoptosis and restricts the severity of demyelination. This review covers aspects related to host defense and disease in response to JHMV infection and highlights the different roles of CXCR2 signaling in these processes.",,"['Marro, Brett S.', 'Hosking, Martin P.', 'Lane, Thomas E.']",,,,
,PMC,Monitoring Data Quality in Syndromic Surveillance: Learnings from a Resource Limited Setting,http://dx.doi.org/10.4103/0974-777X.96778,PMC3385202,22754248,CC BY-NC-SA,"BACKGROUND: India is in the process of integrating all disease surveillance systems with the support of a World Bank funded program called the Integrated Disease Surveillance System. In this context the objective of the study was to evaluate the components of the Orissa Multi Disease Surveillance System. MATERIALS AND METHODS: Multistage sampling was carried out, starting with four districts, followed by sequentially sampling two blocks; and in each block, two sectors and two health sub-centers were selected, all based on the best and worst performances. Two study instruments were developed for data validation, for assessing the components of the surveillance and diagnostic algorithm. The Organizational Ethics Group reviewed and approved the study. RESULTS: In all 178 study subjects participated in the survey. The case definition of suspected meningitis in disease surveillance was found to be difficult, with only 29.94%, who could be correctly identified. Syndromic diagnosis following the diagnostic algorithm was difficult for suspected malaria (28.1%), ‘unusual syndrome’ (28.1%), and simple diarrhea (62%). Only 17% could correctly answer questions on follow-up cases, but only 50% prioritized diseases. Our study showed that 54% cross-checked the data before compilation. Many (22%) faltered on timeliness even during emergencies. The constraints identified were logistics (56%) and telecommunication (41%). The reason for participation in surveillance was job responsibility (34.83%). CONCLUSIONS: Most of the deficiencies arose from human errors when carrying out day-to-day processes of surveillance activities, hence, should be improved by retraining. Enhanced laboratory support and electronic transmission would improve data quality and timeliness. Validity of some of the case definitions need to be rechecked. Training Programs should focus on motivating the surveillance personnel.",2012 Apr-Jun,"['Venkatarao, Epari', 'Patil, Rajan R', 'Prasad, Deepa', 'Anasuya, Anita', 'Samuel, Reuben']",J Glob Infect Dis,,,
,PMC,Provision of pandemic disease information by health sciences librarians: a multisite comparative case series,http://dx.doi.org/10.3163/1536-5050.100.2.008,PMC3324800,,,"OBJECTIVE: The research provides an understanding of pandemic information needs and informs professional development initiatives for librarians in disaster medicine. METHODS: Utilizing a multisite, comparative case series design, the researchers conducted semi-structured interviews and examined supplementary materials in the form of organizational documents, correspondence, and websites to create a complete picture of each case. The rigor of the case series was ensured through data and investigator triangulation. Interview transcripts were coded using NVivo to identify common themes and points of comparison. RESULTS: Comparison of the four cases revealed a distinct difference between “client-initiated” and “librarian-initiated” provision of pandemic information. Librarian-initiated projects utilized social software to “push” information, whereas client-initiated projects operated within patron-determined parameters to deliver information. Health care administrators were identified as a key audience for pandemic information, and news agencies were utilized as essential information sources. Librarians' skills at evaluating available information proved crucial for selecting best-quality evidence to support administrative decision making. CONCLUSIONS: Qualitative analysis resulted in increased understanding of pandemic information needs and identified best practices for disseminating information during periods of high organizational stress caused by an influx of new cases of an unknown infectious disease.",,"['Featherstone, Robin M', 'Boldt, R. Gabriel', 'Torabi, Nazi', 'Konrad, Shauna-Lee']",,,,
,PMC,A novel full-length isoform of murine pregnancy-specific glycoprotein 16 (psg16) is expressed in the brain but does not mediate murine coronavirus (MHV) entry,http://dx.doi.org/10.1007/s13365-012-0081-6,PMC3368079,,,"The mouse pregnancy-specific glycoprotein 16 (PSG16) has been reported to be an alternative receptor for mouse hepatitis virus (MHV), some strains of which cause encephalitis in mice lacking the canonical receptor CEACAM1a. The known isoforms of PSG16 are N-terminally truncated relative to other PSG family proteins and are expressed in neurons as well as in the placenta. We have cloned a novel full-length isoform of psg16 that is also expressed in the brain, placenta, and retina but, like the truncated form, lacks MHV receptor activity when expressed on 293T cells, suggesting that PSG16 does not mediate CEACAM1a-independent spread of MHV.",,"['Phillips, Judith M.', 'Kuo, I-Ting', 'Richardson, Chelsea', 'Weiss, Susan R.']",,,,
,PMC,Hepatitis C Virus Induces CD81 and Claudin-1 Endocytosis,http://dx.doi.org/10.1128/JVI.06996-11,PMC3318669,,,"Hepatitis C virus (HCV) leads to progressive liver disease and hepatocellular carcinoma. Current treatments are only partially effective, and new therapies targeting viral and host pathways are required. Virus entry into a host cell provides a conserved target for therapeutic intervention. Tetraspanin CD81, scavenger receptor class B member I, and the tight-junction proteins claudin-1 and occludin have been identified as essential entry receptors. Limited information is available on the role of receptor trafficking in HCV entry. We demonstrate here that anti-CD81 antibodies inhibit HCV infection at late times after virus internalization, suggesting a role for intracellular CD81 in HCV infection. Several tetraspanins have been reported to internalize via motifs in their C-terminal cytoplasmic domains; however, CD81 lacks such motifs, leading several laboratories to suggest a limited role for CD81 endocytosis in HCV entry. We demonstrate CD81 internalization via a clathrin- and dynamin-dependent process, independent of its cytoplasmic domain, suggesting a role for associated partner proteins in regulating CD81 trafficking. Live cell imaging demonstrates CD81 and claudin-1 coendocytosis and fusion with Rab5 expressing endosomes, supporting a role for this receptor complex in HCV internalization. Receptor-specific antibodies and HCV particles increase CD81 and claudin-1 endocytosis, supporting a model wherein HCV stimulates receptor trafficking to promote particle internalization.",,"['Farquhar, Michelle J.', 'Hu, Ke', 'Harris, Helen J.', 'Davis, Christopher', 'Brimacombe, Claire L.', 'Fletcher, Sarah J.', 'Baumert, Thomas F.', 'Rappoport, Joshua Z.', 'Balfe, Peter', 'McKeating, Jane A.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00474-12,PMC3318655,,,,,,,,,
,PMC,Genetic Evidence of a Long-Range RNA-RNA Interaction between the Genomic 5′ Untranslated Region and the Nonstructural Protein 1 Coding Region in Murine and Bovine Coronaviruses,http://dx.doi.org/10.1128/JVI.06265-11,PMC3318640,,,"Higher-order RNA structures in the 5′ untranslated regions (UTRs) of the mouse hepatitis coronavirus (MHV) and bovine coronavirus (BCoV), separate species in the betacoronavirus genus, appear to be largely conserved despite an ∼36% nucleotide sequence divergence. In a previous study, each of three 5′-end-proximal cis-acting stem-loop domains in the BCoV genome, I/II, III, and IV, yielded near-wild-type (wt) MHV phenotypes when used by reverse genetics to replace its counterpart in the MHV genome. Replacement with the BCoV 32-nucleotide (nt) inter-stem-loop fourth domain between stem-loops III and IV, however, required blind cell passaging for virus recovery. Here, we describe suppressor mutations within the transplanted BCoV 32-nt domain that along with appearance of potential base pairings identify an RNA-RNA interaction between this domain and a 32-nt region ∼200 nt downstream within the nonstructural protein 1 (Nsp1)-coding region. Mfold and phylogenetic covariation patterns among similarly grouped betacoronaviruses support this interaction, as does cotransplantation of the BCoV 5′ UTR and its downstream base-pairing domain. Interestingly, cotransplantation of the BCoV 5′ UTR and BCoV Nsp1 coding region directly yielded an MHV wt-like phenotype, which demonstrates a cognate interaction between these two BCoV regions, which in the MHV genome act in a fully interspecies-compliant manner. Surprisingly, the 30-nt inter-stem-loop domain in the MHV genome can be deleted and viral progeny, although debilitated, are still produced. These results together identify a previously undescribed long-range RNA-RNA interaction between the 5′ UTR and Nsp1 coding region in MHV-like and BCoV-like betacoronaviruses that is cis acting for viral fitness but is not absolutely required for viral replication in cell culture.",,"['Guan, Bo-Jhih', 'Su, Yu-Pin', 'Wu, Hung-Yi', 'Brian, David A.']",,,,
,PMC,The Coronavirus Endoribonuclease Nsp15 Interacts with Retinoblastoma Tumor Suppressor Protein,http://dx.doi.org/10.1128/JVI.07012-11,PMC3318636,,,"Coronaviruses encode an endoribonuclease, Nsp15, which has a poorly defined role in infection. Sequence analysis revealed a retinoblastoma protein-binding motif (LXCXE/D) in the majority of the Nsp15 of the severe acute respiratory syndrome coronavirus (SARS-CoV) and its orthologs in the alpha and beta coronaviruses. The endoribonuclease activity of the SARS-CoV Nsp15 (sNsp15) was stimulated by retinoblastoma protein (pRb) in vitro, and the two proteins can be coimmunoprecipitated from cellular extracts. Mutations in the pRb-binding motif rendered sNsp15 to be differentially modified by ubiquitin in cells, and cytotoxicity was observed upon its expression. Expression of the sNsp15 in cells resulted in an increased abundance of pRb in the cytoplasm, decreased overall levels of pRb, an increased proportion of cells in the S phase of the cell cycle, and an enhanced expression from a promoter normally repressed by pRb. The endoribonuclease activity of the mouse hepatitis virus (MHV) A59 Nsp15 was also increased by pRb in vitro, and an MHV with mutations in the LXCXE/D-motif, named vLC, exhibited a smaller plaque diameter and reduced the virus titer by ∼1 log. Overexpression of pRb delayed the viral protein production by wild-type MHV but not by vLC. This study reveals that pRb and its interaction with Nsp15 can affect coronavirus infection and adds coronaviruses to a small but growing family of RNA viruses that encode a protein to interact with pRb.",,"['Bhardwaj, Kanchan', 'Liu, Pinghua', 'Leibowitz, Julian L.', 'Kao, C. Cheng']",,,,
,PMC,Primary Severe Acute Respiratory Syndrome Coronavirus Infection Limits Replication but Not Lung Inflammation upon Homologous Rechallenge,http://dx.doi.org/10.1128/JVI.06791-11,PMC3318632,,,"Our knowledge regarding immune-protective and immunopathogenic events in severe acute respiratory syndrome coronavirus (SARS-CoV) infection is limited, and little is known about the dynamics of the immune response at the primary site of disease. Here, an African green monkey (AGM) model was used to elucidate immune mechanisms that facilitate viral clearance but may also contribute to persistent lung inflammation following SARS-CoV infection. During primary infection, SARS-CoV replicated in the AGM lung for up to 10 days. Interestingly, lung inflammation was more prevalent following viral clearance, as leukocyte numbers peaked at 14 days postinfection (dpi) and remained elevated at 28 dpi compared to those of mock-infected controls. Lung macrophages but not dendritic cells were rapidly activated, and both cell types had high activation marker expression at late infection time points. Lung proinflammatory cytokines were induced at 1 to 14 dpi, but most returned to baseline by 28 dpi except interleukin 12 (IL-12) and gamma interferon. In SARS-CoV homologous rechallenge studies, 11 of the 12 animals were free of replicating virus at day 5 after rechallenge. However, incidence and severity of lung inflammation was not reduced despite the limited viral replication upon rechallenge. Evaluating the role of antibodies in immune protection or potentiation revealed a progressive increase in anti-SARS-CoV antibodies in lung and serum that did not correlate temporally or spatially with enhanced viral replication. This study represents one of the first comprehensive analyses of lung immunity, including changes in leukocyte populations, lung-specific cytokines, and antibody responses following SARS-CoV rechallenge in AGMs.",,"['Clay, Candice', 'Donart, Nathan', 'Fomukong, Ndingsa', 'Knight, Jennifer B.', 'Lei, Wanli', 'Price, Lance', 'Hahn, Fletcher', 'Van Westrienen, Jesse', 'Harrod, Kevin S.']",,,,
,PMC,Nonstructural Proteins 7 and 8 of Feline Coronavirus Form a 2:1 Heterotrimer That Exhibits Primer-Independent RNA Polymerase Activity,http://dx.doi.org/10.1128/JVI.06635-11,PMC3318631,,,"Nonstructural proteins 7 and 8 of severe acute respiratory syndrome coronavirus (SARS-CoV) have previously been shown by X-ray crystallography to form an 8:8 hexadecamer. In addition, it has been demonstrated that N-terminally His(6)-tagged SARS-CoV Nsp8 is a primase able to synthesize RNA oligonucleotides with a length of up to 6 nucleotides. We present here the 2.6-Å crystal structure of the feline coronavirus (FCoV) Nsp7:Nsp8 complex, which is a 2:1 heterotrimer containing two copies of the α-helical Nsp7 with conformational differences between them, and one copy of Nsp8 that consists of an α/β domain and a long-α-helix domain. The same stoichiometry is found for the Nsp7:Nsp8 complex in solution, as demonstrated by chemical cross-linking, size exclusion chromatography, and small-angle X-ray scattering. Furthermore, we show that FCoV Nsp8, like its SARS-CoV counterpart, is able to synthesize short oligoribonucleotides of up to 6 nucleotides in length when carrying an N-terminal His(6) tag. Remarkably, the same protein harboring the sequence GPLG instead of the His(6) tag at its N terminus exhibits a substantially increased, primer-independent RNA polymerase activity. Upon addition of Nsp7, the RNA polymerase activity is further enhanced so that RNA up to template length (67 nucleotides) can be synthesized. Further, we show that the unprocessed intermediate polyprotein Nsp7-10 of human coronavirus (HCoV) 229E is also capable of synthesizing oligoribonucleotides up to a chain length of six. These results indicate that in case of FCoV as well as of HCoV 229E, the formation of a hexadecameric Nsp7:Nsp8 complex is not necessary for RNA polymerase activity. Further, the FCoV Nsp7:Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.",,"['Xiao, Yibei', 'Ma, Qingjun', 'Restle, Tobias', 'Shang, Weifeng', 'Svergun, Dmitri I.', 'Ponnusamy, Rajesh', 'Sczakiel, Georg', 'Hilgenfeld, Rolf']",,,,
,PMC,Metagenomic Analysis of Viruses from Bat Fecal Samples Reveals Many Novel Viruses in Insectivorous Bats in China,http://dx.doi.org/10.1128/JVI.06671-11,PMC3318625,,,"Increasing data indicate that bats harbor diverse viruses, some of which cause severe human diseases. In this study, sequence-independent amplification and high-throughput sequencing (Solexa) were applied to the metagenomic analysis of viruses in bat fecal samples collected from 6 locations in China. A total of 8,746,417 reads with a length of 306,124,595 bp were obtained. Among these reads, 13,541 (0.15%) had similarity to phage sequences and 9,170 (0.1%) had similarity to eukaryotic virus sequences. A total of 129 assembled contigs (>100 nucleotides) were constructed and compared with GenBank: 32 contigs were related to phages, and 97 were related to eukaryotic viruses. The most frequent reads and contigs related to eukaryotic viruses were homologous to densoviruses, dicistroviruses, coronaviruses, parvoviruses, and tobamoviruses, a range that includes viruses from invertebrates, vertebrates, and plants. Most of the contigs had low identities to known viral genomic or protein sequences, suggesting that a large number of novel and genetically diverse insect viruses as well as putative mammalian viruses are transmitted by bats in China. This study provides the first preliminary understanding of the virome of some bat populations in China, which may guide the discovery and isolation of novel viruses in the future.",,"['Ge, Xingyi', 'Li, Yan', 'Yang, Xinglou', 'Zhang, Huajun', 'Zhou, Peng', 'Zhang, Yunzhi', 'Shi, Zhengli']",,,,
,PMC,Discovery of Retroviral Homologs in Bats: Implications for the Origin of Mammalian Gammaretroviruses,http://dx.doi.org/10.1128/JVI.06624-11,PMC3318619,,,"Gammaretroviruses infect a wide range of vertebrate species where they are associated with leukemias, neurological diseases and immunodeficiencies. However, the origin of these infectious agents is unknown. Through a phylogenetic analysis of viral gene sequences, we show that bats harbor an especially diverse set of gammaretroviruses. In particular, phylogenetic analysis places Rhinolophus ferrumequinum retrovirus (RfRV), a new gammaretrovirus identified by de novo analysis of the Rhinolophus ferrumequinum transcriptome, and six other gammaretroviruses from different bat species, as basal to other mammalian gammaretroviruses. An analysis of the similarity in the phylogenetic history between the gammaretroviruses and their bat hosts provided evidence for both host-virus codivergence and cross-species transmission. Taken together, these data provide new insights into the origin of the mammalian gammaretroviruses.",,"['Cui, Jie', 'Tachedjian, Mary', 'Wang, Lina', 'Tachedjian, Gilda', 'Wang, Lin-Fa', 'Zhang, Shuyi']",,,,
,PMC,Bovine Type III Interferon Significantly Delays and Reduces the Severity of Foot-and-Mouth Disease in Cattle,http://dx.doi.org/10.1128/JVI.06683-11,PMC3318609,,,"Interferons (IFNs) are the first line of defense against viral infections. Although type I and II IFNs have proven effective to inhibit foot-and-mouth disease virus (FMDV) replication in swine, a similar approach had only limited efficacy in cattle. Recently, a new family of IFNs, type III IFN or IFN-λ, has been identified in human, mouse, chicken, and swine. We have identified bovine IFN-λ3 (boIFN-λ3), also known as interleukin 28B (IL-28B), and demonstrated that expression of this molecule using a recombinant replication-defective human adenovirus type 5 (Ad5) vector, Ad5-boIFN-λ3, exhibited antiviral activity against FMDV in bovine cell culture. Furthermore, inoculation of cattle with Ad5-boIFN-λ3 induced systemic antiviral activity and upregulation of IFN-stimulated gene expression in the upper respiratory airways and skin. In the present study, we demonstrated that disease could be delayed for at least 6 days when cattle were inoculated with Ad5-boIFN-λ3 and challenged 24 h later by intradermolingual inoculation with FMDV. Furthermore, the delay in the appearance of disease was significantly prolonged when treated cattle were challenged by aerosolization of FMDV, using a method that resembles the natural route of infection. No clinical signs of FMD, viremia, or viral shedding in nasal swabs was found in the Ad5-boIFN-λ3-treated animals for at least 9 days postchallenge. Our results indicate that boIFN-λ3 plays a critical role in the innate immune response of cattle against FMDV. To this end, this work represents the most successful biotherapeutic strategy so far tested to control FMDV in cattle.",,"['Perez-Martin, Eva', 'Weiss, Marcelo', 'Diaz-San Segundo, Fayna', 'Pacheco, Juan M.', 'Arzt, Jonathan', 'Grubman, Marvin J.', 'de los Santos, Teresa']",,,,
,PMC,The Human Cytomegalovirus-Specific UL1 Gene Encodes a Late-Phase Glycoprotein Incorporated in the Virion Envelope,http://dx.doi.org/10.1128/JVI.06291-11,PMC3318608,,,"We have investigated the previously uncharacterized human cytomegalovirus (HCMV) UL1 open reading frame (ORF), a member of the rapidly evolving HCMV RL11 family. UL1 is HCMV specific; the absence of UL1 in chimpanzee cytomegalovirus (CCMV) and sequence analysis studies suggest that UL1 may have originated by the duplication of an ancestor gene from the RL11-TRL cluster (TRL11, TRL12, and TRL13). Sequence similarity searches against human immunoglobulin (Ig)-containing proteins revealed that HCMV pUL1 shows significant similarity to the cellular carcinoembryonic antigen-related (CEA) protein family N-terminal Ig domain, which is responsible for CEA ligand recognition. Northern blot analysis revealed that UL1 is transcribed during the late phase of the viral replication cycle in both fibroblast-adapted and endotheliotropic strains of HCMV. We characterized the protein encoded by hemagglutinin (HA)-tagged UL1 in the AD169-derived HB5 background. UL1 is expressed as a 224-amino-acid type I transmembrane glycoprotein which becomes detectable at 48 h postinfection. In infected human fibroblasts, pUL1 colocalized at the cytoplasmic site of virion assembly and secondary envelopment together with TGN-46, a marker for the trans-Golgi network, and viral structural proteins, including the envelope glycoprotein gB and the tegument phosphoprotein pp28. Furthermore, analyses of highly purified AD169 UL1-HA epitope-tagged virions revealed that pUL1 is a novel constituent of the HCMV envelope. Importantly, the deletion of UL1 in HCMV TB40/E resulted in reduced growth in a cell type-specific manner, suggesting that pUL1 may be implicated in regulating HCMV cell tropism.",,"['Shikhagaie, Medya', 'Mercé-Maldonado, Eva', 'Isern, Elena', 'Muntasell, Aura', 'Albà, M. Mar', 'López-Botet, Miguel', 'Hengel, Hartmut', 'Angulo, Ana']",,,,
,PMC,The Immune Response to a Vesicular Stomatitis Virus Vaccine Vector Is Independent of Particulate Antigen Secretion and Protein Turnover Rate,http://dx.doi.org/10.1128/JVI.05991-11,PMC3318607,,,"Vesicular stomatitis virus (VSV) is a highly cytopathic virus being developed as a vaccine vector due to its ability to induce strong protective T cell and antibody responses after a single dose. However, little is known regarding the mechanisms underlying the potent immune responses elicited by VSV. We previously generated a VSV vector expressing the hepatitis B virus middle envelope surface glycoprotein (MS) that induces strong MS-specific T cell and antibody responses in mice. After synthesis in the cytoplasm, the MS protein translocates to the endoplasmic reticulum, where it forms subviral particles that are secreted from the cell. To better understand the contributions of secreted and intracellular protein to the VSV-induced immune response, we produced a vector expressing a secretion-deficient MS mutant (MS(C69A)) and compared the immunogenicity of this vector to that of the wild-type VSV-MS vector in mice. As expected, the MS(C69A) protein was not secreted from VSV-infected cells and displayed enhanced proteasome-mediated degradation. Surprisingly, despite these differences in intracellular protein processing, the T cell and antibody responses generated to MS(C69A) were comparable to those elicited by virus expressing wild-type MS protein. Therefore, when it is expressed from VSV, the immune responses to MS are independent of particulate antigen secretion and the turnover rate of cytoplasmic protein. These results are consistent with a model in which the immune responses to VSV are strongly influenced by the replication cycle of the vector and demonstrate that characteristics of the vector have the capacity to affect vaccine efficacy more than do the properties of the antigen itself.",,"['Cobleigh, Melissa A.', 'Bradfield, Clinton', 'Liu, Yuanjie', 'Mehta, Anand', 'Robek, Michael D.']",,,,
,PMC,Herpes Simplex Virus 1 Tegument Protein US11 Downmodulates the RLR Signaling Pathway via Direct Interaction with RIG-I and MDA-5,http://dx.doi.org/10.1128/JVI.06713-11,PMC3302539,,,"The interferon (IFN)-mediated antiviral response is a major defense of the host immune system. In order to complete their life cycle, viruses must modulate host IFN-mediated immune responses. Herpes simplex virus 1 (HSV-1) is a large DNA virus containing more than 80 genes, many of which encode proteins that are involved in virus-host interactions and show immune modulatory capabilities. In this study, we demonstrate that the US11 protein, an RNA binding tegument protein of HSV-1, is a novel antagonist of the beta IFN (IFN-β) pathway. US11 significantly inhibited Sendai virus (SeV)-induced IFN-β production, and its double-stranded RNA (dsRNA) binding domain was indispensable for this inhibition activity. Additionally, wild-type HSV-1 coinfection showed stronger inhibition than US11 mutant HSV-1 in SeV-induced IFN-β production. Coimmunoprecipitation analysis demonstrated that the US11 protein in HSV-1-infected cells interacts with endogenous RIG-I and MDA-5 through its C-terminal RNA-binding domain, which was RNA independent. Expression of US11 in both transfected and HSV-1-infected cells interferes with the interaction between MAVS and RIG-I or MDA-5. Finally, US11 dampens SeV-mediated IRF3 activation. Taken together, the combined data indicate that HSV-1 US11 binds to RIG-I and MDA-5 and inhibits their downstream signaling pathway, preventing the production of IFN-β, which may contribute to the pathogenesis of HSV-1 infection.",,"['Xing, Junji', 'Wang, Shuai', 'Lin, Rongtuan', 'Mossman, Karen L.', 'Zheng, Chunfu']",,,,
,PMC,Arterivirus Minor Envelope Proteins Are a Major Determinant of Viral Tropism in Cell Culture,http://dx.doi.org/10.1128/JVI.06836-11,PMC3302522,,,"Arteriviruses are enveloped positive-strand RNA viruses for which the attachment proteins and cellular receptors have remained largely controversial. Arterivirus particles contain at least eight envelope proteins, an unusually large number among RNA viruses. These appear to segregate into three groups: major structural components (major glycoprotein GP5 and membrane protein [M]), minor glycoproteins (GP2a, GP3, and GP4), and small hydrophobic proteins (E and the recently discovered ORF5a protein). Biochemical studies previously suggested that the GP5-M heterodimer of porcine reproductive and respiratory syndrome virus (PRRSV) interacts with porcine sialoadhesin (pSn) in porcine alveolar macrophages (PAM). However, another study proposed that minor protein GP4, along with GP2a, interacts with CD163, another reported cellular receptor for PRRSV. In this study, we provide genetic evidence that the minor envelope proteins are the major determinant of arterivirus entry into cultured cells. A PRRSV infectious cDNA clone was equipped with open reading frames (ORFs) encoding minor envelope and E proteins of equine arteritis virus (EAV), the only known arterivirus displaying a broad tropism in cultured cells. Although PRRSV and EAV are only distantly related and utilize diversified transcription-regulating sequences (TRSs), a viable chimeric progeny virus was rescued. Strikingly, this chimeric virus (vAPRRS-EAV2ab34) acquired the broad in vitro cell tropism of EAV, demonstrating that the minor envelope proteins play a critical role as viral attachment proteins. We believe that chimeric arteriviruses of this kind will be a powerful tool for further dissection of the arterivirus replicative cycle, including virus entry, subgenomic RNA synthesis, and virion assembly.",,"['Tian, Debin', 'Wei, Zuzhang', 'Zevenhoven-Dobbe, Jessika C.', 'Liu, Runxia', 'Tong, Guangzhi', 'Snijder, Eric J.', 'Yuan, Shishan']",,,,
,PMC,Nonstructural Protein 2 of Porcine Reproductive and Respiratory Syndrome Virus Inhibits the Antiviral Function of Interferon-Stimulated Gene 15,http://dx.doi.org/10.1128/JVI.06466-11,PMC3302520,,,"Type I interferon (alpha/beta interferon [IFN-α/β]) stimulates the expression of interferon-stimulated gene 15 (ISG15), which encodes a ubiquitin-like protein, ISG15. Free ISG15 and ISG15 conjugates function in diverse cellular pathways, particularly regulation of antiviral innate immune responses. In this study, we demonstrate that ISG15 overexpression inhibits porcine reproductive and respiratory syndrome virus (PRRSV) replication in cell culture and that the antiviral activity of interferon is reduced by inhibition of ISG15 conjugation. PRRSV nonstructural protein 2 (nsp2) was previously identified as a potential antagonist of ISG15 production and conjugation. The protein contains a papain-like protease domain (PLP2) that plays a crucial role in the proteolytic cleavage of the PRRSV replicase polyproteins. PLP2 was also proposed to belong to the ovarian tumor domain-containing superfamily of deubiquitinating enzymes (DUBs), which is capable of inhibiting ISG15 production and counteracting ISG15 conjugation to cellular proteins. To determine whether this immune antagonist function could be selectively inactivated, we engineered a panel of mutants with deletions and/or mutations at the N-terminal border of the nsp2 PLP2-DUB domain. A 23-amino-acid deletion (amino acids 402 to 424 of the ORF1a-encoded protein) largely abolished the inhibitory effect of nsp2 on ISG15 production and conjugation, but no viable recombinant virus was recovered. A 19-amino-acid deletion (amino acids 402 to 420), in combination with a downstream point mutation (S465A), partially relieved the ISG15 antagonist function and yielded a viable recombinant virus. Taken together, our data demonstrate that ISG15 and ISGylation play an important role in the response to PRRSV infection and that nsp2 is a key factor in counteracting the antiviral function of ISG15.",,"['Sun, Zhi', 'Li, Yanhua', 'Ransburgh, Russell', 'Snijder, Eric J.', 'Fang, Ying']",,,,
,PMC,An Antibody Recognizing the Apical Domain of Human Transferrin Receptor 1 Efficiently Inhibits the Entry of All New World Hemorrhagic Fever Arenaviruses,http://dx.doi.org/10.1128/JVI.06397-11,PMC3302512,,,"Five New World (NW) arenaviruses cause human hemorrhagic fevers. Four of these arenaviruses are known to enter cells by binding human transferrin receptor 1 (hTfR1). Here we show that the fifth arenavirus, Chapare virus, similarly uses hTfR1. We also identify an anti-hTfR1 antibody, ch128.1, which efficiently inhibits entry mediated by the glycoproteins of all five viruses, as well as replication of infectious Junín virus. Our data indicate that all NW hemorrhagic fever arenaviruses utilize a common hTfR1 apical-domain epitope and suggest that therapeutic agents targeting this epitope, including ch128.1 itself, can be broadly effective in treating South American hemorrhagic fevers.",,"['Helguera, Gustavo', 'Jemielity, Stephanie', 'Abraham, Jonathan', 'Cordo, Sandra M.', 'Martinez, M. Guadalupe', 'Rodríguez, José A.', 'Bregni, Carlos', 'Wang, Jinyize J.', 'Farzan, Michael', 'Penichet, Manuel L.', 'Candurra, Nélida A.', 'Choe, Hyeryun']",,,,
,PMC,West Nile Virus Infections Suppress Early Viral RNA Synthesis and Avoid Inducing the Cell Stress Granule Response,http://dx.doi.org/10.1128/JVI.06549-11,PMC3302502,,,"West Nile virus (WNV) recently became endemic in the United States and is a significant cause of human morbidity and mortality. Natural WNV strain infections do not induce stress granules (SGs), while W956IC (a lineage 2/1 chimeric WNV infectious clone) virus infections produce high levels of early viral RNA and efficiently induce SGs through protein kinase R (PKR) activation. Additional WNV chimeric viruses made by replacing one or more W956IC genes with the lineage 1 Eg101 equivalent in the W956IC backbone were analyzed. The Eg-NS4b+5, Eg-NS1+3+4a, and Eg-NS1+4b+5 chimeras produced low levels of viral RNA at early times of infection and inefficiently induced SGs, suggesting the possibility that interactions between viral nonstructural proteins and/or between viral nonstructural proteins and cell proteins are involved in suppressing early viral RNA synthesis and membrane remodeling during natural WNV strain infections. Detection of exposed viral double-stranded RNA (dsRNA) in W956IC-infected cells suggested that the enhanced early viral RNA synthesis surpassed the available virus-induced membrane protection and allowed viral dsRNA to activate PKR.",,"['Courtney, S. C.', 'Scherbik, S. V.', 'Stockman, B. M.', 'Brinton, M. A.']",,,,
,PMC,Discovery of Seven Novel Mammalian and Avian Coronaviruses in the Genus Deltacoronavirus Supports Bat Coronaviruses as the Gene Source of Alphacoronavirus and Betacoronavirus and Avian Coronaviruses as the Gene Source of Gammacoronavirus and Deltacoronavirus,http://dx.doi.org/10.1128/JVI.06540-11,PMC3302495,,,"Recently, we reported the discovery of three novel coronaviruses, bulbul coronavirus HKU11, thrush coronavirus HKU12, and munia coronavirus HKU13, which were identified as representatives of a novel genus, Deltacoronavirus, in the subfamily Coronavirinae. In this territory-wide molecular epidemiology study involving 3,137 mammals and 3,298 birds, we discovered seven additional novel deltacoronaviruses in pigs and birds, which we named porcine coronavirus HKU15, white-eye coronavirus HKU16, sparrow coronavirus HKU17, magpie robin coronavirus HKU18, night heron coronavirus HKU19, wigeon coronavirus HKU20, and common moorhen coronavirus HKU21. Complete genome sequencing and comparative genome analysis showed that the avian and mammalian deltacoronaviruses have similar genome characteristics and structures. They all have relatively small genomes (25.421 to 26.674 kb), the smallest among all coronaviruses. They all have a single papain-like protease domain in the nsp3 gene; an accessory gene, NS6 open reading frame (ORF), located between the M and N genes; and a variable number of accessory genes (up to four) downstream of the N gene. Moreover, they all have the same putative transcription regulatory sequence of ACACCA. Molecular clock analysis showed that the most recent common ancestor of all coronaviruses was estimated at approximately 8100 BC, and those of Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus were at approximately 2400 BC, 3300 BC, 2800 BC, and 3000 BC, respectively. From our studies, it appears that bats and birds, the warm blooded flying vertebrates, are ideal hosts for the coronavirus gene source, bats for Alphacoronavirus and Betacoronavirus and birds for Gammacoronavirus and Deltacoronavirus, to fuel coronavirus evolution and dissemination.",,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Lam, Carol S. F.', 'Lau, Candy C. Y.', 'Tsang, Alan K. L.', 'Lau, John H. N.', 'Bai, Ru', 'Teng, Jade L. L.', 'Tsang, Chris C. C.', 'Wang, Ming', 'Zheng, Bo-Jian', 'Chan, Kwok-Hung', 'Yuen, Kwok-Yung']",,,,
,PMC,Decontamination of Bacillus subtilis var. niger spores on selected surfaces by chlorine dioxide gas,http://dx.doi.org/10.1631/jzus.B1100289,PMC3323940,,,"Objective: Chlorine dioxide (CD) gas has been used as a fumigant in the disinfection of biosafety laboratories. In this study, some experiments were conducted to assess the inactivation of spores inoculated on six materials [stainless steel (SS), painted steel (PS), polyvinyl chlorid (PVC), polyurethane (PU), glass (GS), and cotton cloth (CC)] by CD gas. The main aims of the study were to determine the sporicidal efficacy of CD gas and the effect of prehumidification before decontamination on sporicidal efficacy. Methods: Material coupons (1.2 cm diameter of SS, PS, and PU; 1.0 cm×1.0 cm for PVC, GS, and CC) were contaminated with 10 μl of Bacillus subtilis var. niger (ATCC 9372) spore suspension in mixed organic burden and then dried in a biosafety cabinet for 12 h. The spores were recovered by soaking the coupons in 5 ml of extraction liquid for 1 h and then vortexing the liquid for 1 min. Results: The log reductions in spore numbers on inoculated test materials exposed to CD gas [0.080% (volume ratio, v/v) for 3 h] were in the range of from 1.80 to 6.64. Statistically significant differences were found in decontamination efficacies on test material coupons of SS, PS, PU, and CC between with and without a 1-h prehumidification treatment. With the extraction method, there were no statistically significant differences in the recovery ratios between the porous and non-porous materials. Conclusions: The results reported from this study could provide information for developing decontamination technology based on CD gas for targeting surface microbial contamination.",,"['Li, Yan-ju', 'Zhu, Neng', 'Jia, Hai-quan', 'Wu, Jin-hui', 'Yi, Ying', 'Qi, Jian-cheng']",,,,
,PMC,Activation status of integrated stress response pathways in neurones and astrocytes of HIV-associated neurocognitive disorders (HAND) cortex,http://dx.doi.org/10.1111/j.1365-2990.2011.01215.x,PMC3708539,,,"AIMS: Combined anti-retroviral therapy (cART) has led to a reduction in the incidence of HIV-associated dementia (HAD), a severe motor/cognitive disorder afflicting HIV(+) patients. However, the prevalence of subtler forms of neurocognitive dysfunction, which together with HAD are termed HIV-associated neurocognitive disorders (HAND), continues to escalate in the post-cART era. The microgliosis, astrogliosis, dendritic damage, and synaptic and neuronal loss observed in autopsy cases suggest an underlying neuroinflammatory process, due to the neurotoxic factors released by HIV-infected/activated macrophages/ microglia in the brain, might underlie the pathogenesis of HAND in the post-cART era. These factors are known to induce the integrated stress response (ISR) in several neurodegenerative diseases; we have previously shown that BiP, an indicator of general ISR activation, is upregulated in cortical autopsy tissue from HIV-infected patients. The ISR is composed of three pathways, each with its own initiator protein: PERK, IRE1α and ATF6. METHODS: To further elucidate the specific ISR pathways activated in the central nervous system of HAND patients, we examined the protein levels of several ISR proteins, including ATF6, peIF2α and ATF4, in cortical tissue from HIV-infected patients. RESULTS: The ISR does not respond in an all-or-none fashion in HAND, but rather demonstrates a nuanced activation pattern. Specifically, our studies implicate the ATF6 pathway of the ISR as a more likely candidate than the PERK pathway for increases in BiP levels in astrocytes. CONCLUSION: These findings begin to characterize the nature of the ISR response in HAND and provide potential targets for therapeutic intervention in this disease.",,"['Akay, C.', 'Lindl, K. A.', 'Shyam, N.', 'Nabet, B.', 'Goenaga-Vazquez, Y.', 'Ruzbarsky, J.', 'Wang, Y.', 'Kolson, D. L.', 'Jordan-Sciutto, K. L.']",,,,
,PMC,Presence of Viral Nucleic Acids in the Middle Ear: Acute Otitis Media Pathogen or Bystander?,http://dx.doi.org/10.1097/INF.0b013e318241afe4,PMC3305843,,,"Viruses play an important role in acute otitis media (AOM) pathogenesis and live viruses may cause AOM in absence of pathogenic bacteria. Detection of AOM pathogens generally relies on bacterial culture of middle ear fluid. When viral culture is used and live viruses are detected in the middle ear fluid of children with AOM, the viruses are generally accepted as AOM pathogens. Because viral culture is not sensitive and does not detect the comprehensive spectrum of respiratory viruses, polymerase chain reaction (PCR) assays are commonly used to detect viral nucleic acids in the middle ear fluid. While PCR assays have greatly increased the viral detection rate, new questions arise on the significance of viral nucleic acids detected in the middle ear because nucleic acids of multiple viruses are detected simultaneously, and nucleic acids of specific viruses are detected repeatedly and in a high proportion of asymptomatic children. This article first reviews the role of live viruses in AOM and presents the point-counter point arguments on whether viral nucleic acids in the middle ear represent an AOM pathogen or a bystander status. While there is evidence to support both directions, helpful information for interpretation of the data and future research direction are outlined.",,"['CHONMAITREE, TASNEE', 'RUOHOLA, AINO', 'HENDLEY, J. OWEN']",,,,
,PMC,Absence of Gastrointestinal Pathogens in Ileum Tissue Resected for Necrotizing Enterocolitis,http://dx.doi.org/10.1097/INF.0b013e318242534a,PMC3305842,,,"Necrotizing enterocolitis (NEC) is the one of the most common gastrointestinal emergencies in premature infants and has been linked with viral antigens for as much as 40% of cases in single center cohorts. We examined 28 tissue sections from surgically resected ileum from 27 preterm infants with NEC from 2 separate institutions for 15 common bacterial, viral, and parasitic gastrointestinal pathogens using multiplex RT-PCR amplification and suspension array detection methods. We did not detect infectious enteritis pathogens in any of the NEC tissues and conclude that gastrointestinal pathogens are a rare cause of NEC.",,"['ULLRICH, TIM', 'TANG, YI-WEI', 'CORREA, HERNAN', 'GARZON, STEVEN A.', 'MAHESHWARI, AKHIL', 'HILL, MELISSA', 'MATTA, PRANATHI', 'KRISHNAN, MOHAN K.', 'WEITKAMP, JÖRN-HENDRIK']",,,,
,PMC,THE DELICATE BALANCE BETWEEN SECRETED PROTEIN FOLDING AND ENDOPLASMIC RETICULUM-ASSOCIATED DEGRADATION IN HUMAN PHYSIOLOGY,http://dx.doi.org/10.1152/physrev.00027.2011,PMC4162396,,,"Protein folding is a complex, error-prone process that often results in an irreparable protein by-product. These by-products can be recognized by cellular quality control machineries and targeted for proteasome-dependent degradation. The folding of proteins in the secretory pathway adds another layer to the protein folding “problem,” as the endoplasmic reticulum maintains a unique chemical environment within the cell. In fact, a growing number of diseases are attributed to defects in secretory protein folding, and many of these by-products are targeted for a process known as endoplasmic reticulum-associated degradation (ERAD). Since its discovery, research on the mechanisms underlying the ERAD pathway has provided new insights into how ERAD contributes to human health during both normal and diseases states. Links between ERAD and disease are evidenced from the loss of protein function as a result of degradation, chronic cellular stress when ERAD fails to keep up with misfolded protein production, and the ability of some pathogens to coopt the ERAD pathway. The growing number of ERAD substrates has also illuminated the differences in the machineries used to recognize and degrade a vast array of potential clients for this pathway. Despite all that is known about ERAD, many questions remain, and new paradigms will likely emerge. Clearly, the key to successful disease treatment lies within defining the molecular details of the ERAD pathway and in understanding how this conserved pathway selects and degrades an innumerable cast of substrates.",,"['Guerriero, Christopher J.', 'Brodsky, Jeffrey L.']",,,,
,PMC,Synthesis of 5′ cap-0 and cap-1 RNAs using solid-phase chemistry coupled with enzymatic methylation by human (guanine-N(7))-methyl transferase,http://dx.doi.org/10.1261/rna.030932.111,PMC3312571,,,"The 5′ end of eukaryotic mRNA carries a N(7)-methylguanosine residue linked by a 5′-5′ triphosphate bond. This cap moiety ((7m)GpppN) is an essential RNA structural modification allowing its efficient translation, limiting its degradation by cellular 5′ exonucleases and avoiding its recognition as “nonself” by the innate immunity machinery. In vitro synthesis of capped RNA is an important bottleneck for many biological studies. Moreover, the lack of methods allowing the synthesis of large amounts of RNA starting with a specific 5′-end sequence have hampered biological and structural studies of proteins recognizing the cap structure or involved in the capping pathway. Due to the chemical nature of N(7)-methylguanosine, the synthesis of RNAs possessing a cap structure at the 5′ end is still a significant challenge. In the present work, we combined a chemical synthesis method and an enzymatic methylation assay in order to produce large amounts of RNA oligonucleotides carrying a cap-0 or cap-1. Short RNAs were synthesized on solid support by the phosphoramidite 2′-O-pivaloyloxymethyl chemistry. The cap structure was then coupled by the addition of GDP after phosphorylation of the terminal 5′-OH and activation by imidazole. After deprotection and release from the support, GpppN-RNAs or GpppN(2′-Om)-RNAs were purified before the N(7)-methyl group was added by enzymatic means using the human (guanine-N(7))-methyl transferase to yield (7m)GpppN-RNAs (cap-0) or (7m)GpppN(2′-Om)-RNAs (cap-1). The RNAs carrying different cap structures (cap, cap-0 or, cap-1) act as bona fide substrates mimicking cellular capped RNAs and can be used for biochemical and structural studies.",,"['Thillier, Yann', 'Decroly, Etienne', 'Morvan, François', 'Canard, Bruno', 'Vasseur, Jean-Jacques', 'Debart, Françoise']",,,,
,PMC,Detection of Infectious Influenza Virus in Cough Aerosols Generated in a Simulated Patient Examination Room,http://dx.doi.org/10.1093/cid/cis237,PMC4680957,,,"BACKGROUND: The potential for aerosol transmission of infectious influenza virus (ie, in healthcare facilities) is controversial. We constructed a simulated patient examination room that contained coughing and breathing manikins to determine whether coughed influenza was infectious and assessed the effectiveness of an N95 respirator and surgical mask in blocking transmission. METHODS: National Institute for Occupational Safety and Health aerosol samplers collected size-fractionated aerosols for 60 minutes at the mouth of the breathing manikin, beside the mouth, and at 3 other locations in the room. Total recovered virus was quantitated by quantitative polymerase chain reaction and infectivity was determined by the viral plaque assay and an enhanced infectivity assay. RESULTS: Infectious influenza was recovered in all aerosol fractions (5.0% in >4 µm aerodynamic diameter, 75.5% in 1–4 µm, and 19.5% in <1 µm; n = 5). Tightly sealing a mask to the face blocked entry of 94.5% of total virus and 94.8% of infectious virus (n = 3). A tightly sealed respirator blocked 99.8% of total virus and 99.6% of infectious virus (n = 3). A poorly fitted respirator blocked 64.5% of total virus and 66.5% of infectious virus (n = 3). A mask documented to be loosely fitting by a PortaCount fit tester, to simulate how masks are worn by healthcare workers, blocked entry of 68.5% of total virus and 56.6% of infectious virus (n = 2). CONCLUSIONS: These results support a role for aerosol transmission and represent the first reported laboratory study of the efficacy of masks and respirators in blocking inhalation of influenza in aerosols. The results indicate that a poorly fitted respirator performs no better than a loosely fitting mask.",,"['Noti, John D.', 'Lindsley, William G.', 'Blachere, Francoise M.', 'Cao, Gang', 'Kashon, Michael L.', 'Thewlis, Robert E.', 'McMillen, Cynthia M.', 'King, William P.', 'Szalajda, Jonathan V.', 'Beezhold, Donald H.']",,,,
,PMC,The Complication of Coinfection,,PMC3313527,,,"Infectious disease remains one of the largest burdens on humankind. Even with modern medical and public health standards, infectious disease remained the No. 1 killer worldwide at the turn of the century. Often, the most costly disease burdens come from multiple infections at once, i.e., coinfection. Influenza, an annual infection often considered relatively harmless, can increase susceptibility to both deadly bacterial pneumonia and childhood ear infections. Major health threat HIV rarely kills a patient on its own, but instead allows for opportunistic infections and re-emergence of infections such as tuberculosis. What generates these unique relationships is not well understood; herein, we examine in detail three types of coinfection and the unique interactions between infectious agents as well as with the host in each setting. We also begin to address how we may aid further understanding of coinfection and what questions need to be addressed to help direct future treatments.",,"Pasman, Lesley",,,,
,PMC,Examining the positive effects of exercise in intubated adults in ICU: A prospective repeated measures clinical study,http://dx.doi.org/10.1016/j.iccn.2012.02.007,PMC3783509,,,"BACKGROUND: Determining the optimal timing and progression of mobility exercise has the potential to affect functional recovery of critically ill adults. This study compared standard care with care delivered using a mobility protocol. We examined the effects of exercise on vital signs and inflammatory biomarkers and the effects of the nurse-initiated mobility protocol on outcomes. METHODS: Prospective, repeated measures study with a control (standard care) and intervention (protocol) period. RESULTS: 75 heterogeneous subjects admitted to a Medical or Surgical intensive care unit (ICU) were enrolled. In <5% of exercise periods, there was a concerning alteration in respiratory rate or peripheral oxygen saturation; no other adverse events occurred. Findings suggested the use of a protocol with one 20 minute episode of exercise daily for 2 or more days reduced ICU length of stay. Duration of exercise was linked to increased IL-10, suggesting brief episodes of low intensity exercise positively altered inflammatory dysregulation in this sample. CONCLUSION: A growing body of evidence demonstrates that early, progressive exercise has significant benefits to intubated adults. These results should encourage clinicians to add mobility protocols to the care of ICU adults and lead to future studies to determine optimal “dosing” of exercise in ICU patients.",,"['Winkelman, Chris', 'Johnson, Kimberly D.', 'Hejal, Rana', 'Gordon, Nahida H.', 'Rowbottom, James', 'Daly, Janis', 'Peereboom, Karen', 'Levine, Alan D.']",,,,
,PMC,A virus-like particle vaccine platform elicits heightened and hastened local lung mucosal antibody production after a single dose,http://dx.doi.org/10.1016/j.vaccine.2012.03.035,PMC3579574,,,"We show that a model antigen, ovalbumin (OVA), can be chemically conjugated to the exterior of a small heat shock protein (sHsp) cage that has structural similarities to virus-like particles (VLPs). OVA-sHsp conjugation efficiency was dependent upon the stoichiometry and the length of the small molecule linker utilized, and the attachment position on the sHsp cage. When conjugated OVA-sHsp was delivered intranasally to naïve mice, the resulting immune response to OVA was accelerated and intensified, and OVA-specific IgG1 responses were apparent within 5 days after a single immunizing dose, illustrating its utility for vaccine development. If animals were pretreated with a disparate VLP, P22 (a non-replicative bacteriophage capsid), before OVA-sHsp conjugate immunization, OVA-specific IgG1 responses were apparent already by 4 days after a single immunizing dose of conjugate in OVA-naïve mice. Additionally, the mice pretreated with P22 produced high titer mucosal IgA, and isotype-switched OVA-specific serum IgG. Similarly, sHsp pretreatment enhanced the accumulation of lung germinal center B cells, T follicular helper cells, and increased polymeric Ig receptor expression, priming the lungs for subsequent IgG and IgA responses to influenza virus challenge. Thus, sHsp nanoparticles elicited quick and intense antibody responses and these accelerated responses could similarly be induced to antigen chemically conjugated to the sHsp. Pretreatment of mice with P22 further accelerated the onset of the antibody response to OVA-sHsp, demonstrating the utility of conjugating antigens to VLPs for pre-, or possibly post-exposure prophylaxis of lung, all without the need for adjuvant.",,"['Richert, Laura E.', 'Servid, Amy E.', 'Harmsen, Ann L.', 'Rynda-Apple, Agnieszka', 'Han, Soo', 'Wiley, James A.', 'Douglas, Trevor', 'Harmsen, Allen G.']",,,,
,PMC,The Future of Research and Publication on Altered H5N1 Viruses,http://dx.doi.org/10.1093/infdis/jis257,PMC3415850,,,"Recently, we and others obtained experimental evidence that highly pathogenic avian influenza virus subtype H5 can acquire the ability to transmit via aerosols between ferrets. Upon submission of manuscripts describing the results of these studies, the US National Science Advisory Board for Biosecurity was consulted and recommended that the main conclusions of the work be published but without the experimental details and mutation data that would enable replication of the experiments. Over the past few months, these events have led to intense discussions. Should this type of experiment be conducted? If so, under what conditions? Do the scientific and public health benefits of the work and its publication outweigh the potential risks? In February 2012, public health and influenza experts discussed these issues during a World Health Organization–organized technical consultation. This perspective article reviews the current state of the field and the recommendations made during the meeting.",,"['Herfst, Sander', 'Osterhaus, Albert D. M. E.', 'Fouchier, Ron A. M.']",,,,
,PMC,A decade of gains in public health emergency preparedness and response at points of entry,http://dx.doi.org/10.5365/WPSAR.2012.3.1.003,PMC3729068,,,,,"['Roohi, Shahrokh', 'Wilson, Todd']",,,,
,PMC,In vitro Transcription and Capping of Gaussia Luciferase mRNA Followed by HeLa Cell Transfection,http://dx.doi.org/10.3791/3702,PMC3460589,,,"In vitro transcription is the synthesis of RNA transcripts by RNA polymerase from a linear DNA template containing the corresponding promoter sequence (T7, T3, SP6) and the gene to be transcribed (Figure 1A). A typical transcription reaction consists of the template DNA, RNA polymerase, ribonucleotide triphosphates, RNase inhibitor and buffer containing Mg(2+) ions. Large amounts of high quality RNA are often required for a variety of applications. Use of in vitro transcription has been reported for RNA structure and function studies such as splicing(1), RNAi experiments in mammalian cells(2), antisense RNA amplification by the ""Eberwine method""(3), microarray analysis(4) and for RNA vaccine studies(5). The technique can also be used for producing radiolabeled and dye labeled probes(6). Warren, et al. recently reported reprogramming of human cells by transfection with in vitro transcribed capped RNA(7). The T7 High Yield RNA Synthesis Kit from New England Biolabs has been designed to synthesize up to 180 μg RNA per 20 μl reaction. RNA of length up to 10kb has been successfully transcribed using this kit. Linearized plasmid DNA, PCR products and synthetic DNA oligonucleotides can be used as templates for transcription as long as they have the T7 promoter sequence upstream of the gene to be transcribed. Addition of a 5' end cap structure to the RNA is an important process in eukaryotes. It is essential for RNA stability(8), efficient translation(9), nuclear transport(10) and splicing(11). The process involves addition of a 7-methylguanosine cap at the 5' triphosphate end of the RNA. RNA capping can be carried out post-transcriptionally using capping enzymes or co-transcriptionally using cap analogs. In the enzymatic method, the mRNA is capped using the Vaccinia virus capping enzyme(12,13). The enzyme adds on a 7-methylguanosine cap at the 5' end of the RNA using GTP and S-adenosyl methionine as donors (cap 0 structure). Both methods yield functionally active capped RNA suitable for transfection or other applications(14) such as generating viral genomic RNA for reverse-genetic systems(15) and crystallographic studies of cap binding proteins such as eIF4E(16). In the method described below, the T7 High Yield RNA Synthesis Kit from NEB is used to synthesize capped and uncapped RNA transcripts of Gaussia luciferase (GLuc) and Cypridina luciferase (CLuc). A portion of the uncapped GLuc RNA is capped using the Vaccinia Capping System (NEB). A linearized plasmid containing the GLuc or CLuc gene and T7 promoter is used as the template DNA. The transcribed RNA is transfected into HeLa cells and cell culture supernatants are assayed for luciferase activity. Capped CLuc RNA is used as the internal control to normalize GLuc expression.",,"['Jani, Bhairavi', 'Fuchs, Ryan']",,,,
,PMC,Gastrointestinal inflammation and associated immune activation in schizophrenia,http://dx.doi.org/10.1016/j.schres.2012.02.025,PMC4244845,,,"Immune factors are implicated in normal brain development and in brain disorder pathogenesis. Pathogen infection and food antigen penetration across gastrointestinal barriers are means by which environmental factors might affect immune-related neurodevelopment. Here, we test if gastrointestinal inflammation is associated with schizophrenia and therefore, might contribute to bloodstream entry of potentially neurotropic milk and gluten exorphins and/or immune activation by food antigens. IgG antibodies to Saccharomyces cerevisiae (ASCA, a marker of intestinal inflammation), bovine milk casein, wheat-derived gluten, and 6 infectious agents were assayed. Cohort 1 included 193 with non-recent onset schizophrenia, 67 with recent onset schizophrenia and 207 non-psychiatric controls. Cohort 2 included 103 with first episode schizophrenia, 40 of whom were antipsychotic-naïve. ASCA markers were significantly elevated and correlated with food antigen antibodies in recent onset and non-recent onset schizophrenia compared to controls (p ≤ 0.00001–0.004) and in unmedicated individuals with first episode schizophrenia compared to those receiving antipsychotics (p ≤ 0.05–0.01). Elevated ASCA levels were especially evident in non-recent onset females (p ≤ 0.009), recent onset males (p ≤ 0.01) and in antipsychotic-naïve males (p ≤ 0.03). Anti-food antigen antibodies were correlated to antibodies against Toxoplasma gondii, an intestinally-infectious pathogen, particularly in males with recent onset schizophrenia (p ≤ 0.002). In conclusion, gastrointestinal inflammation is a relevant pathology in schizophrenia, appears to occur in the absence of but may be modified by antipsychotics, and may link food antigen sensitivity and microbial infection as sources of immune activation in mental illness.",,"['Severance, Emily G.', 'Alaedini, Armin', 'Yang, Shuojia', 'Halling, Meredith', 'Gressitt, Kristin L.', 'Stallings, Cassie R.', 'Origoni, Andrea E.', 'Vaughan, Crystal', 'Khushalani, Sunil', 'Leweke, F. Markus', 'Dickerson, Faith B.', 'Yolken, Robert H.']",,,,
,PMC,Quercetin inhibits rhinovirus replication in vitro and in vivo,http://dx.doi.org/10.1016/j.antiviral.2012.03.005,PMC3360794,,,"Rhinovirus (RV), which is responsible for the majority of common colds, also causes exacerbations in patients with asthma and chronic obstructive pulmonary disease. So far, there are no drugs available for treatment of rhinovirus infection. We examined the effect of quercetin, a plant flavanol on RV infection in vitro and in vivo. Pretreatment of airway epithelial cells with quercetin decreased Akt phosphosphorylation, viral endocytosis and IL-8 responses. Addition of quercetin 6 h after RV infection (after viral endocytosis) reduced viral load, IL-8 and IFN responses in airway epithelial cells. This was associated with decreased levels of negative and positive strand viral RNA, and RV capsid protein, abrogation of RV-induced eIF4GI cleavage and increased phosphorylation of eIF2α. In mice infected with RV, quercetin treatment decreased viral replication as well as expression of chemokines and cytokines. Quercetin treatment also attenuated RV-induced airway cholinergic hyperresponsiveness. Together, our results suggest that quercetin inhibits RV endocytosis and replication in airway epithelial cells at multiple stages of the RV life cycle. Quercetin also decreases expression of pro-inflammatory cytokines and improves lung function in RV-infected mice. Based on these observations, further studies examining the potential benefits of quercetin in the prevention and treatment of RV infection are warranted.",,"['Ganesan, Shyamala', 'Faris, Andrea N.', 'Comstock, Adam T.', 'Wang, Qiong', 'Nanua, Suparna', 'Hershenson, Marc B.', 'Sajjan, Uma S.']",,,,
,PMC,Filovirus Entry into Cells – New Insights,http://dx.doi.org/10.1016/j.coviro.2012.02.015,PMC3322298,,,"Filoviruses are hemorrhagic fever-causing agents that produce enveloped virions with a filamentous morphology. The viral surface glycoprotein, GP, orchestrates the surprisingly complex process by which filoviruses gain access to the cytoplasm of their host cells. GP mediates viral attachment to cells through multiple, redundant interactions with cell-surface factors. GP then induces virion internalization by a process that resembles cellular macropinocytosis. Within the endo/lysosomal pathway, GP undergoes a series of structural rearrangements, controlled by interactions with host factors, that prime and activate it to bring about fusion between the viral and cellular lipid bilayers. Membrane fusion delivers the viral nucleocapsid core into the cytoplasm, which is the site of filovirus replication. This review summarizes our understanding of the filovirus entry mechanism, with emphasis on recent findings.",,"['Happy Miller, Emily', 'Chandran, Kartik']",,,,
,PMC,Novel Approaches to Flavivirus Drug Discovery,http://dx.doi.org/10.1517/17460441.2012.673579,PMC6190671,,,"INTRODUCTION: The members of the family Flaviviridae, including West Nile virus, yellow fever virus, and dengue virus, are important human pathogens that are expanding their impact around the globe. The four serotypes of dengue infect 50 to 100 million people each year, yet the only clinical treatment is supportive care to reduce symptoms. Drugs that employ novel inhibition mechanisms and targets are urgently needed to combat the growing incidence of dengue worldwide. AREAS COVERED: The authors discuss recently discovered flavivirus inhibitors with a focus on antivirals targeting non-enzymatic proteins of the dengue virus lifecycle. Specifically, the authors discuss the flaviviruses, the need for novel inhibitors, and the criteria for successful antiviral drug development. Current literature describing new advances in antiviral therapy at each stage of the flavivirus life cycle (entry, endosomal escape, viral RNA processing and replication, assembly, and immune evasion) are evaluated and summarized. EXPERT OPINION: Overall, the prognosis of flavivirus antiviral drug development is positive: new effective compounds have been discovered and studied. However, repurposing existing compounds and a greater translation to the clinical setting are recommended in order to combat the growing threat of flaviviruses.",,"['Botting, Carolyn', 'Kuhn, Richard J.']",,,,
,PMC,Correction,http://dx.doi.org/10.1016/j.bpj.2012.02.040,PMC3309288,,,,,,,,,
,PMC,Acute fibrinous and organising pneumonia,http://dx.doi.org/10.1136/bcr.01.2011.3689,PMC3316785,,,"Acute fibrinous and organising pneumonia (AFOP) was recently described as an unusual pattern of diffuse lung disease. Particular characteristics make the differential diagnosis with the well recognised clinical patterns of diffuse alveolar damage, cryptogenic organising pneumonia or eosinophilic pneumonia. The lack of hyaline membranes, the presence of intra-alveolar fibrin, absence of noticeable eosinophils and patchy distribution suggests that AFOP define a distinct histological pattern. The authors describe the case of a woman diagnosed with AFOP after surgical lung biopsy, in association with primary biliary cirrhosis. The patient presented dyspnoea, fatigue, dry cough and thoracic pain. The CT scan showed bilateral patchy infiltrates predominantly in the lower lobes. Flexible bronchoscopy and subsidiary techniques were inconclusive and biopsy through video-assisted thoracoscopic surgery led to anatomopathological diagnosis of AFOP. The patient is having a good clinical response to prednisone.",,"['Guimarães, Catarina', 'Sanches, Inês', 'Ferreira, Catarina']",,,,
,PMC,The non-human primate model of tuberculosis,http://dx.doi.org/10.1111/j.1600-0684.2012.00536.x,PMC3961469,,,"Non-human primates (NHPs) are used to model human disease owing to their remarkably similar genomes, physiology, and immune systems. Recently, there has been an increased interest in modeling tuberculosis (TB) in NHPs. Macaques are susceptible to infection with different strains of Mycobacterium tuberculosis (Mtb), producing the full spectrum of disease conditions, including latent infection, chronic progressive infection, and acute TB, depending on the route and dose of infection. Clearly, NHPs are an excellent model of human TB. While the initial aim of the NHP model was to allow preclinical testing of candidate vaccines and drugs, it is now also being used to study pathogenesis and immune correlates of protection. Recent advances in this field are discussed in this review. Key questions such as the effect of hypoxia on the biology of Mtb and the basis of reactivation of latent TB can now be investigated through the use of this model.",,"['Kaushal, D.', 'Mehra, S.', 'Didier, P.J.', 'Lackner, A.A.']",,,,
,PMC,Dendritic Cell Targeted Chitosan Nanoparticles for Nasal DNA Immunization against SARS CoV Nucleocapsid Protein,http://dx.doi.org/10.1021/mp200553x,PMC3322645,,,"This work investigates the formulation and in vivo efficacy of dendritic cell (DC) targeted plasmid DNA loaded biotinylated chitosan nanoparticles for nasal immunization against nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) as antigen. The induction of antigen-specific mucosal and systemic immune response at the site of virus entry is a major challenge for vaccine design. Here, we designed a strategy for non-invasive receptor mediated gene delivery to nasal resident DCs. The pDNA loaded biotinylated chitosan nanoparticles were prepared using a complex coacervation process and characterized for size, shape, surface charge, plasmid loading and protection against nuclease digestion. The pDNA loaded biotinylated chitosan nanoparticles were targeted with bifunctional fusion protein (bfFp) vector for achieving DC selective targeting. The bfFp is a recombinant fusion protein consisting of truncated core-streptavidin fused with anti-DEC-205 single chain antibody (scFv). The core-streptavidin arm of fusion protein binds with biotinylated nanoparticles, while anti-DEC-205 scFv imparts targeting specificity to DC DEC-205 receptor. We demonstrate that intranasal administration of bfFp targeted formulations along with anti-CD40 DC maturation stimuli enhanced magnitude of mucosal IgA as well as systemic IgG against N protein. The strategy led to the detection of augmented levels of N protein specific systemic IgG and nasal IgA antibodies. However, following intranasal delivery of naked pDNA no mucosal and systemic immune responses were detected. A parallel comparison of targeted formulations using intramuscular and intranasal route showed that the intramuscular route is superior for induction of systemic IgG responses compared with the intranasal route. Our results suggest that targeted pDNA delivery through non-invasive intranasal route can be a strategy for designing low-dose vaccines.",,"['Raghuwanshi, Dharmendra', 'Mishra, Vivek', 'Das, Dipankar', 'Kaur, Kamaljit', 'Suresh, Mavanur R.']",,,,
,PMC,Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age,http://dx.doi.org/10.1073/pnas.1109797109,PMC3326453,,,"T cell-dependent B-cell responses decline with age, suggesting defective CD4 T-cell function. CD4 memory T cells from individuals older than 65 y displayed increased and sustained transcription of the dual-specific phosphatase 4 (DUSP4) that shortened expression of CD40-ligand (CD40L) and inducible T-cell costimulator (ICOS) (both P < 0.001) and decreased production of IL-4, IL-17A, and IL-21 (all P < 0.001) after in vitro activation. In vivo after influenza vaccination, activated CD4 T cells from elderly individuals had increased DUSP4 transcription (P = 0.002), which inversely correlated with the expression of CD40L (r = 0.65, P = 0.002), ICOS (r = 0.57, P = 0.008), and IL-4 (r = 0.66, P = 0.001). In CD4 KO mice reconstituted with DUSP4 OT-II T cells, DUSP4 had a negative effect on the expansion of antigen-specific B cells (P = 0.003) and the production of ova-specific antibodies (P = 0.03) after immunization. Silencing of DUSP4 in memory CD4 T cells improved CD40L (P < 0.001), IL-4 (P = 0.007), and IL-21 (P = 0.04) expression significantly more in the elderly than young adults. Consequently, the ability of CD4 memory T cells to support B-cell differentiation that was impaired in the elderly (P = 0.004) was restored. Our data suggest that increased DUSP4 expression in activated T cells in the elderly in part accounts for defective adaptive immune responses.",,"['Yu, Mingcan', 'Li, Guangjin', 'Lee, Won-Woo', 'Yuan, Ming', 'Cui, Dapeng', 'Weyand, Cornelia M.', 'Goronzy, Jörg J.']",,,,
,PMC,"Feline morbillivirus, a previously undescribed paramyxovirus associated with tubulointerstitial nephritis in domestic cats",http://dx.doi.org/10.1073/pnas.1119972109,PMC3325679,,,"We describe the discovery and isolation of a paramyxovirus, feline morbillivirus (FmoPV), from domestic cat (Felis catus). FmoPV RNA was detected in 56 (12.3%) of 457 stray cats (53 urine, four rectal swabs, and one blood sample) by RT-PCR. Complete genome sequencing of three FmoPV strains showed genome sizes of 16,050 bases, the largest among morbilliviruses, because of unusually long 5′ trailer sequences of 400 nt. FmoPV possesses identical gene contents (3′-N-P/V/C-M-F-H-L-5′) and is phylogenetically clustered with other morbilliviruses. IgG against FmoPV N protein was positive in 49 sera (76.7%) of 56 RT-PCR–positive cats, but 78 (19.4%) of 401 RT-PCR–negative cats (P < 0.0001) by Western blot. FmoPV was isolated from CRFK feline kidney cells, causing cytopathic effects with cell rounding, detachment, lysis, and syncytia formation. FmoPV could also replicate in subsequent passages in primate Vero E6 cells. Infected cell lines exhibited finely granular and diffuse cytoplasmic fluorescence on immunostaining for FmoPV N protein. Electron microscopy showed enveloped virus with typical “herringbone” appearance of helical N in paramyxoviruses. Histological examination of necropsy tissues in two FmoPV-positive cats revealed interstitial inflammatory infiltrate and tubular degeneration/necrosis in kidneys, with decreased cauxin expression in degenerated tubular epithelial cells, compatible with tubulointerstitial nephritis (TIN). Immunohistochemical staining revealed FmoPV N protein-positive renal tubular cells and mononuclear cells in lymph nodes. A case-control study showed the presence of TIN in seven of 12 cats with FmoPV infection, but only two of 15 cats without FmoPV infection (P < 0.05), suggesting an association between FmoPV and TIN.",,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Wong, Beatrice H. L.', 'Fan, Rachel Y. Y.', 'Wong, Annette Y. P.', 'Zhang, Anna J. X.', 'Wu, Ying', 'Choi, Garnet K. Y.', 'Li, Kenneth S. M.', 'Hui, Janet', 'Wang, Ming', 'Zheng, Bo-Jian', 'Chan, K. H.', 'Yuen, Kwok-Yung']",,,,
,PMC,Colonization properties of Campylobacter jejuni in chickens,http://dx.doi.org/10.1556/EuJMI.2.2012.1.9,PMC3933991,,,"Campylobacter is the most common bacterial food-borne pathogen worldwide. Poultry and specifically chicken and raw chicken meat is the main source for human Campylobacter infection. Whilst being colonized by Campylobacter spp. chicken in contrast to human, do scarcely develop pathological lesions. The immune mechanisms controlling Campylobacter colonization and infection in chickens are still not clear. Previous studies and our investigations indicate that the ability to colonize the chicken varies significantly not only between Campylobacter strains but also depending on the original source of the infecting isolate. The data provides circumstantial evidence that early immune mechanisms in the gut may play an important role in the fate of Campylobacter in the host.",,"['Pielsticker, C.', 'Glünder, G.', 'Rautenschlein, S.']",,,,
,PMC,Olig1 function is required for remyelination potential of transplanted neural progenitor cells in a model of viral-induced demyelination,http://dx.doi.org/10.1016/j.expneurol.2012.03.003,PMC3350784,,,"Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) resulting in cumulative neurologic deficits associated with progressive myelin loss. We have previously shown that transplantation of neural progenitor cells (NPCs) into mice persistently infected with the JHM strain of mouse hepatitis virus (JHMV) results in enhanced differentiation into oligodendrocyte progenitor cells (OPCs) that is associated with remyelination and axonal sparing. The current study examines the contributions of the transcription factor Olig1 on NPC differentiation and remyelination. Under defined conditions, NPCs preferentially differentiate into oligodendroglia whereas NPCs isolated from Olig1-deficient (Olig1−/−) mice exhibit enhanced differentiation into astrocytes. Transplantation of Olig1−/− and Olig1+/+ NPCs into JHMV-infected mice resulted in similar cell survival, proliferation, and selective migration to areas of demyelination. However, only recipients of wild type NPCs exhibited extensive remyelination compared to mice receiving Olig1−/− NPCs. In vivo characterization of NPCs revealed that Olig1+/+ NPCs preferentially differentiated into NG2-positive OPCs and formed processes expressing myelin basic protein that encircled axons. In contrast, the majority of transplanted Olig1−/− NPCs differentiated into GFAP-positive cells consistent with the astrocyte lineage. These results indicate that exogenous NPCs contribute to improved clinical and histological outcome and this is associated with remyelination by this donor population. Further, these findings reveal that Olig1function is required for the remyelination potential of NPCs after transplant, through specification and/or maintenance of oligodendroglial identity.",,"['Whitman, Lucia M.', 'Blanc, Caroline A.', 'Schaumburg, Chris S.', 'Rowitch, David H.', 'Lane, Thomas E.']",,,,
,PMC,The Spleen is the Major Source of Anti-Donor Antibody Secreting Cells in Murine Heart Allograft Recipients,http://dx.doi.org/10.1111/j.1600-6143.2012.04009.x,PMC3381891,,,"Antibody mediated allograft rejection is an increasingly recognized problem in clinical transplantation. However, the primary location of donor specific alloantibody (DSA) producing cells after transplantation have not been identified. The purpose of this study was to test the contribution of allospecific antibody secreting cells (ASCs) from different anatomical compartments in a mouse transplantation model. Fully MHC-mismatched heart allografts were transplanted into three groups of recipients: non-sensitized wild type, alloantigen-sensitized wild type and CCR5(−/−) mice that have exaggerated alloantibody responses. We found that previous sensitization to donor alloantigens resulted in the development of anti-donor alloantibody (alloAb) with accelerated kinetics. Nevertheless, the numbers of alloantibody secreting cells and the serum titers of anti-donor IgG alloantibody were equivalent in sensitized and non-sensitized recipients six weeks after transplantation. Regardless of recipient sensitization status, the spleen contained higher numbers of donor-reactive ASCs than bone marrow at days 7–21 after transplantation. Furthermore, individual spleen ASCs produced more anti-donor IgG alloantibody than bone marrow ASCs. Taken together, our results indicate that the spleen rather than bone marrow is the major source of donor-reactive alloAb early after transplantation in both sensitized and non-sensitized recipients.",,"['Sicard, Antoine', 'Phares, Timothy W.', 'Yu, Hong', 'Fan, Ran', 'Baldwin, William M.', 'Fairchild, Robert L.', 'Valujskikh, Anna']",,,,
,PMC,Increased Risk of Noninfluenza Respiratory Virus Infections Associated With Receipt of Inactivated Influenza Vaccine,http://dx.doi.org/10.1093/cid/cis307,PMC3404712,,,"We randomized 115 children to trivalent inactivated influenza vaccine (TIV) or placebo. Over the following 9 months, TIV recipients had an increased risk of virologically-confirmed non-influenza infections (relative risk: 4.40; 95% confidence interval: 1.31-14.8). Being protected against influenza, TIV recipients may lack temporary non-specific immunity that protected against other respiratory viruses.",,"['Cowling, Benjamin J.', 'Fang, Vicky J.', 'Nishiura, Hiroshi', 'Chan, Kwok-Hung', 'Ng, Sophia', 'Ip, Dennis K. M.', 'Chiu, Susan S.', 'Leung, Gabriel M.', 'Peiris, J. S. Malik']",,,,
,PMC,"Animal virus discovery: improving animal health, understanding zoonoses, and opportunities for vaccine development",http://dx.doi.org/10.1016/j.coviro.2012.02.012,PMC3378828,,,"The characterization of viral genomes has accelerated due to improvement in DNA sequencing technology. Sources of animal samples and molecular methods for the identification of novel viral pathogens and steps to determine their pathogenicity are listed. The difficulties for predicting future cross-species transmissions are highlighted by the wide diversity of known viral zoonoses. Recent surveys of viruses in wild and domesticated animals have characterized numerous viruses including some closely related to those infecting humans. The detection of multiple genetic lineages within viral families infecting a single host species, phylogenetically interspersed with viruses found in other host species, reflects frequent past cross-species transmissions. Numerous opportunities for the generation of novel vaccines will arise from a better understanding of animal viromes.",,"Delwart, Eric",,,,
,PMC,MHC Class II Tetramers,http://dx.doi.org/10.4049/jimmunol.1102398,PMC3297979,,,"MHC Class II tetramers have emerged as an important tool for characterization of the specificity and phenotype of CD4 T cell immune responses, useful in a large variety of disease and vaccine studies. Issues of specific T cell frequency, biodistribution, and avidity, coupled with the large genetic diversity of potential class II restriction elements, require targeted experimental design. Translational opportunities for immune disease monitoring are driving rapid development of HLA class II tetramer use in clinical applications, together with innovations in tetramer production and epitope discovery.",,"Nepom, Gerald T",,,,
,PMC,Plasmacytoid dendritic cell depletion leads to an enhanced mononuclear phagocyte response in lungs of mice with lethal influenza virus infection,http://dx.doi.org/10.1016/j.cimid.2012.01.012,PMC3368063,,,"Plasmacytoid dendritic cells (pDCs) have been implicated both in the control and pathogenesis of influenza virus infection. We demonstrate that pDC depletion has marked effects on the response of mononuclear phagocytes, including conventional DCs (cDCs) and macrophages, to lethal influenza virus infection. Infection of mice lacking pDCs through antibody-mediated depletion resulted in substantially increased accumulation of mononuclear phagocytes and their progenitors in lungs compared to non-treated controls. pDC ablation resulted in a 5- to 35-fold enhancement of intracellular TNF-α and IL-6 production from inflammatory cDCs and exudate macrophages. Purified pulmonary cDCs and macrophages cultured from pDC-depleted mice produced significantly elevated levels of pro-inflammatory cytokines and chemokines compared to pDC-intact counterparts. Elimination of pDCs resulted in decreased lung IFN-α and an immediate and transient reduction in lung virus burden but did not impact disease outcome. These data reveal a suppressive effect of pDCs on the inflammatory response to influenza virus infection in the lung.",,"['Soloff, Adam C.', 'Weirback, Heather K.', 'Ross, Ted M.', 'Barratt-Boyes, Simon M.']",,,,
,PMC,An animal model that reflects human disease: the common marmoset (Callithrix jacchus),http://dx.doi.org/10.1016/j.coviro.2012.02.007,PMC3378983,,,"The common marmoset is a new world primate belonging to the Callitrichidae family weighing between 350 and 400g. The marmoset has been shown to be an outstanding model for studying aging, reproduction, neuroscience, toxicology, and infectious disease. With regard to their susceptibility to infectious agents, they are exquisite NHP models for viral, protozoan and bacterial agents, as well as prions. The marmoset provides the advantages of a small animal model in high containment coupled with the immunological repertoire of a nonhuman primate and susceptibility to wild type, non-adapted viruses.",,"['Carrion, Ricardo', 'Patterson, Jean L.']",,,,
,PMC,Antimicrobial peptides: agents of border protection for companion animals,http://dx.doi.org/10.1111/j.1365-3164.2012.01037.x,PMC3467306,,,"Over the past 20 years, there have been significant inroads into understanding the roles of antimicrobial peptides in homeostatic functions and their involvement in disease pathogenesis. In addition to direct antimicrobial activity, these peptides participate in many cellular functions, including chemotaxis, wound healing, and even determination of canine coat colour. Various biologic and genetic approaches have helped to elucidate the role of antimicrobial peptide with respect innate immunity and host defense. Associations of antimicrobial peptides with various skin diseases, including psoriasis, rosacea and atopic dermatitis, have been documented in humans. In the longer term, therapeutic modulation of antimicrobial peptide expression may provide effective new treatments for disease. This review highlights current knowledge about antimicrobial peptides of the skin and circulating leukocytes, with particular focus on relevance to physiology and disease in companion animals.",,"['Leonard, Brian C.', 'Affolter, Verena K.', 'Bevins, Charles L.']",,,,
,PMC,Regulating the adaptive immune response to respiratory virus infection,http://dx.doi.org/10.1038/nri3166,PMC3364025,,,"Recent years have seen several advances in our understanding of immunity to virus infection of the lower respiratory tract, including to influenza virus infection. Here, we review the cellular targets of viruses and the features of the host immune response that are unique to the lungs. We describe the interplay between innate and adaptive immune cells in the induction, expression and control of antiviral immunity, and discuss the impact of the infected lung milieu on moulding the response of antiviral effector T cells. Recent findings on the mechanisms that underlie the increased frequency of severe pulmonary bacterial infections following respiratory virus infection are also discussed.",,"['Braciale, Thomas J.', 'Sun, Jie', 'Kim, Taeg S.']",,,,
,PMC,Identifying an immune signature against invasive Salmonella,http://dx.doi.org/10.1073/pnas.1201825109,PMC3324022,,,,,"['Ferreira, Rosana B. R.', 'Finlay, B. Brett']",,,,
,PMC,Astrovirus in wild boars (Sus scrofa) in Hungary,http://dx.doi.org/10.1007/s00705-012-1272-4,PMC3506007,,,"The family Astroviridae consists of two genera, Avastrovirus and Mamastrovirus whose members are associated with gastroenteritis in avian and mammalian hosts, respectively. In this study, we report the first detection of astrovirus from fecal specimens of wild boars (Sus scrofa) using viral metagenomics and complete genome sequencing. The wild boar astrovirus (WBAstV-1/2011/HUN, JQ340310) genome is 6707 nucleotide long and had 76%, 95% and 56% amino acid (aa) identity in the ORF1a (852aa), ORF1b (522aa) and ORF2 (845aa) regions, respectively, to porcine astrovirus 4 (PAstV-4, JF713713), the closest match. This study indicates that wild boar could be a reservoir for astroviruses.",,"['Reuter, Gábor', 'Nemes, Csaba', 'Boros, Ákos', 'Kapusinszky, Beatrix', 'Delwart, Eric', 'Pankovics, Péter']",,,,
,PMC,Modeling the Step of Endosomal Escape during Cell Infection by a Nonenveloped Virus,http://dx.doi.org/10.1016/j.bpj.2011.12.037,PMC3302482,,,"Widely disparate viruses enter the host cell through an endocytic pathway and travel the cytoplasm inside an endosome. For the viral genetic material to be delivered into the cytoplasm, these viruses have to escape the endosomal compartment, an event triggered by the conformational changes of viral endosomolytic proteins. We focus here on small nonenveloped viruses such as adeno-associated viruses, which contain few penetration proteins. The first time a penetration protein changes conformation defines the slowest timescale responsible for the escape. To evaluate this time, we construct what to our knowledge is a novel biophysical model based on a stochastic approach that accounts for the small number of proteins, the endosomal maturation, and the protease activation dynamics. We show that the escape time increases with the endosomal size, whereas decreasing with the number of viral particles inside the endosome. We predict that the optimal escape probability is achieved when the number of proteases in the endosome is in the range of 250–350, achieved for three viral particles.",,"['Lagache, Thibault', 'Danos, Olivier', 'Holcman, David']",,,,
,PMC,Ubiquitination-mediated regulation of interferon responses,http://dx.doi.org/10.3109/08977194.2012.669382,PMC3703147,,,"Interferon cytokine family members shape the immune response to protect the host from both pathologic infections and tumorigenesis. To mediate their physiologic function, interferons evoke a robust and complex signal transduction pathway that leads to the induction of interferon-stimulated genes with both proinflammatory and anti-viral function. Numerous mechanisms exist to tightly regulate the extent and duration of these cellular responses. Among such mechanisms, the post-translational conjugation of ubiquitin polypeptides to protein mediators of interferon signaling has emerged as a crucially important mode of control. In this mini-review we highlight recent advances in our understanding of these ubiquitin-mediated mechanisms, their exploitation by invading viruses and their possible utilization for medical intervention.",,"Fuchs, Serge Y.",,,,
,PMC,Correction: SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b,http://dx.doi.org/10.1371/annotation/64ae6047-0f9b-4d17-a065-e08c153aa435,PMC3297658,,CC BY,,2012 Mar 7,"['Varshney, Bhavna', 'Agnihothram, Sudhakar', 'Tan, Yee-Joo', 'Baric, Ralph', 'Lal, Sunil K.']",PLoS One,,,
,PMC,Regulation of stress granules in virus systems,http://dx.doi.org/10.1016/j.tim.2012.02.001,PMC3322245,,,,,"['White, James P.', 'Lloyd, Richard E.']",,,,
,PMC,Risk of infection following a visit to the emergency department: a cohort study,http://dx.doi.org/10.1503/cmaj.110372,PMC3291696,,,"BACKGROUND: The risk of infection following a visit to the emergency department is unknown. We explored this risk among elderly residents of long-term care facilities. METHODS: We compared the rates of new respiratory and gastrointestinal infections among elderly residents aged 65 years and older of 22 long-term care facilities. We used standardized surveillance definitions. For each resident who visited the emergency department during the study period, we randomly selected two residents who did not visit the emergency department and matched them by facility unit, age and sex. We calculated the rates and proportions of new infections, and we used conditional logistic regression to adjust for potential confounding variables. RESULTS: In total, we included 1269 residents of long-term care facilities, including 424 who visited the emergency department during the study. The baseline characteristics of residents who did or did not visit the emergency department were similar, except for underlying health status (visited the emergency department: mean Charlson Comorbidity Index 6.1, standard deviation [SD] 2.5; did not visit the emergency department: mean Charlson Comorbidity index 5.5, SD 2.7; p < 0.001) and the proportion who had visitors (visited the emergency department: 46.9%; did not visit the emergency department: 39.2%; p = 0.01). Overall, 21 (5.0%) residents who visited the emergency department and 17 (2.0%) who did not visit the emergency department acquired new infections. The incidence of new infections was 8.3/1000 patient-days among those who visited the emergency department and 3.4/1000 patient-days among those who did not visit the emergency department. The adjusted odds ratio for the risk of infection following a visit to the emergency department was 3.9 (95% confidence interval 1.4–10.8). INTERPRETATION: A visit to the emergency department was associated with more than a threefold increased risk of acute infection among elderly people. Additional precautions should be considered for residents following a visit to the emergency department.",,"['Quach, Caroline', 'McArthur, Margaret', 'McGeer, Allison', 'Li, Lynne', 'Simor, Andrew', 'Dionne, Marc', 'Lévesque, Edith', 'Tremblay, Lucie']",,,,
,PMC,Influenza A Virus Neuraminidase Protein Enhances Cell Survival through Interaction with Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 (CEACAM6) Protein,http://dx.doi.org/10.1074/jbc.M111.328070,PMC3340274,,,"The influenza virus neuraminidase (NA) protein primarily aids in the release of progeny virions from infected cells. Here, we demonstrate a novel role for NA in enhancing host cell survival by activating the Src/Akt signaling axis via an interaction with carcinoembryonic antigen-related cell adhesion molecule 6/cluster of differentiation 66c (C6). NA/C6 interaction leads to increased tyrosyl phosphorylation of Src, FAK, Akt, GSK3β, and Bcl-2, which affects cell survival, proliferation, migration, differentiation, and apoptosis. siRNA-mediated suppression of C6 resulted in a down-regulation of activated Src, FAK, and Akt, increased apoptosis, and reduced expression of viral proteins and viral titers in influenza virus-infected human lung adenocarcinoma epithelial and normal human bronchial epithelial cells. These findings indicate that influenza NA not only aids in the release of progeny virions, but also cell survival during viral replication.",,"['Gaur, Pratibha', 'Ranjan, Priya', 'Sharma, Shipra', 'Patel, Jenish R.', 'Bowzard, J. Bradford', 'Rahman, Shah K.', 'Kumari, Rashmi', 'Gangappa, Shivaprakash', 'Katz, Jacqueline M.', 'Cox, Nancy J.', 'Lal, Renu B.', 'Sambhara, Suryaprakash', 'Lal, Sunil K.']",,,,
,PMC,ANTIBODY FUSIONS REDUCE ONSET OF EXPERIMENTAL CRYPTOSPORIDIUM PARVUM INFECTION IN CALVES,http://dx.doi.org/10.1016/j.vetpar.2012.02.014,PMC3387522,,,"Cryptosporidium parvum is one of the main causes of diarrhea in neonatal calves resulting in significant morbidity and economic losses for producers worldwide. We have previously demonstrated efficacy of a new class of antimicrobial antibody fusions in a neonatal mouse model for C. parvum infection. Here, we extend efficacy testing of these products to experimental infection in calves, the principal target species. Neonatal calves were challenged with C. parvum oocysts and concomitantly treated with antibody-biocide fusion 4H9-G1-LL37 over the course of four days. This resulted in reduced severity of the disease when compared to control animals. Overall clinical health parameters showed significant improvement in treated animals. Oocyst shedding was reduced in treated when compared to control animals. Control of oocyst shedding is a prerequisite for breaking the cycle of re-infection on dairy farms. Antibody-biocide fusion products thus have the potential to reduce the impact of the infection in both individual animals and in the herd.",,"['Imboden, Michael', 'Schaefer, Deborah A.', 'Bremel, Robert D.', 'Homan, E. Jane', 'Riggs, Michael W.']",,,,
,PMC,Recent advances involving the renin–angiotensin system,http://dx.doi.org/10.1016/j.yexcr.2012.02.023,PMC3625040,,,"The renin–angiotensin system (RAS) exercises fundamental control over sodium and water handling in the kidney. Accordingly, dysregulation of the RAS leads to blood pressure elevation with ensuing renal and cardiovascular damage. Recent studies have revealed that the RAS hormonal cascade is more complex than initially posited with multiple enzymes, effector molecules, and receptors that coordinately regulate the effects of the RAS on the kidney and vasculature. Moreover, recently identified tissue-specific RAS components have pleomorphic effects independent of the circulating RAS that influence critical homeostatic mechanisms including the immune response and fetal development. Further characterization of the diverse interactions between the RAS and other signaling pathways within specific tissues should lead to novel treatments for renal and cardiovascular disease.",,"['Crowley, Steven D.', 'Coffman, Thomas M.']",,,,
,PMC,Urbanisation and health in China,http://dx.doi.org/10.1016/S0140-6736(11)61878-3,PMC3733467,,,"China has seen the largest human migration in history, and the country's rapid urbanisation has important consequences for public health. A provincial analysis of its urbanisation trends shows shifting and accelerating rural-to-urban migration across the country and accompanying rapid increases in city size and population. The growing disease burden in urban areas attributable to nutrition and lifestyle choices is a major public health challenge, as are troubling disparities in health-care access, vaccination coverage, and accidents and injuries in China's rural-to-urban migrant population. Urban environmental quality, including air and water pollution, contributes to disease both in urban and in rural areas, and traffic-related accidents pose a major public health threat as the country becomes increasingly motorised. To address the health challenges and maximise the benefits that accompany this rapid urbanisation, innovative health policies focused on the needs of migrants and research that could close knowledge gaps on urban population exposures are needed.",,"['Gong, Peng', 'Liang, Song', 'Carlton, Elizabeth J', 'Jiang, Qingwu', 'Wu, Jianyong', 'Wang, Lei', 'Remais, Justin V']",,,,
,PMC,Impact of Relative Humidity and Collection Media on Mycobacteriophage D29 Aerosol,http://dx.doi.org/10.1128/AEM.06610-11,PMC3294485,,,"This study was conducted to evaluate the effect of aerosol generation, methods of sampling, storage conditions, and relative humidity on the culturability of the mycobacteriophage D29. The lytic phage D29 can kill Mycobacterium tuberculosis, and the phage aerosol can be treated as a potential tool for tuberculosis treatment. The culturability of D29 was tested using a test chamber designed for the bioaerosols research against three spray liquids (deionized water, phosphate-buffered saline [PBS], and normal saline), four collection media (suspension medium [SM], nutrient broth, PBS, and deionized water), two sampling systems (the all-glass impinger AGI-30 and the Biosampler) and across a range of humidities (20 to 90%). The effect of storage conditions on the culturability of collected sample was also evaluated for the AGI-30 impinger. The results proved that viable phage D29 particles generated by deionized water were approximately 30- and 300-fold higher than PBS and normal saline, respectively. As collection media, SM buffer and nutrient broth were observed to yield a higher number of plaques compared to PBS and deionized water. No difference was observed in collection efficiency between AGI-30 and Biosampler with two detection methods (culture-based technique and real-time PCR). The culturability of collected D29 in SM buffer or nutrient broth can be maintained up to 12 h irrespective of storage temperature. Relative humidity was found to strongly influence airborne D29 culturability which is 2- to 20-fold higher in low humidity (25%) than medium (55%) or high (85%) humidity. This research will help identify the optimal means for the application of D29 aerosol in animal inhalation experiments.",,"['Liu, Keyang', 'Wen, Zhanbo', 'Li, Na', 'Yang, Wenhui', 'Wang, Jie', 'Hu, Lingfei', 'Dong, Xiaokai', 'Lu, Jianchun', 'Li, Jinsong']",,,,
,PMC,Lactobacillus acidophilus and L. reuteri modulate cytokine responses in gnotobiotic pigs infected with human rotavirus,http://dx.doi.org/10.3920/BM2011.0041,PMC3304463,,,"Probiotic lactic acid bacteria (LAB) have been shown to alleviate inflammation, enhance the immunogenicity of rotavirus vaccines, or reduce the severity of rotavirus diarrhoea. Although the mechanisms are not clear, the differential Th1/Th2/Th3-driving capacities and modulating effects on cytokine production of different LAB strains may be the key. Our goal was to delineate the influence of combining two probiotic strains L. acidophilus and L. reuteri on the development of cytokine responses in neonatal gnotobiotic pigs infected with human rotavirus (HRV). We demonstrated that HRV alone, or HRV plus LAB, but not LAB alone, initiated serum cytokine responses, as indicated by significantly higher concentrations of IFN-α, IFN-γ, IL-12, and IL-10 at post-inoculation day (PID) 2 in the HRV only and LAB+HRV+ pigs compared to LAB only and LAB-HRV- pigs. Peak cytokine responses coincided with the peak of HRV replication. LAB further enhanced the Th1 and Th2 cytokine responses to HRV infection as indicated by significantly higher concentrations of IL-12, IFN-γ, IL-4 and IL-10 in the LAB+HRV+ pigs compared to the LAB-HRV+ pigs. The LAB+HRV+ pigs maintained relatively constant concentrations of TGF-β compared to the HRV only group which had a significant increase at PID 2 and decrease at PID 7, suggesting a regulatory role of LAB in maintaining gut homeostasis. At PID 28, cytokine secreting cell (CSC) responses, measured by ELISpot, showed increased Th1 (IL-12, IFN-γ) CSC numbers in the LAB+HRV+ and LAB-HRV+ groups compared to LAB only and LAB-HRV- pigs, with significantly increased IL-12 CSCs in spleen and PBMCs and IFN-γ CSCs in spleen of the LAB+HRV+ group. Thus, HRV infection alone, but not LAB alone was effective in inducing cytokine responses but LAB significantly enhanced both Th1 and Th2 cytokines in HRV-infected pigs. LAB may also help to maintain immunological homeostasis during HRV infection by regulating TGF-β production.",,"['Azevedo, M. S. P.', 'Zhang, W.', 'Wen, K.', 'Gonzalez, A. M.', 'Saif, L. J.', 'Yousef, A. E.', 'Yuan, L.']",,,,
,PMC,Modification of the avian coronavirus infectious bronchitis virus for vaccine development,http://dx.doi.org/10.4161/bbug.18983,PMC3357331,,,"Infectious bronchitis virus (IBV) causes an infectious respiratory disease of domestic fowl that affects poultry of all ages causing economic problems for the poultry industry worldwide. Although IBV is controlled using live attenuated and inactivated vaccines it continues to be a major problem due to the existence of many serotypes, determined by the surface spike protein resulting in poor cross-protection, and loss of immunogenicity associated with vaccine production. Live attenuated IBV vaccines are produced by the repeated passage in embryonated eggs resulting in spontaneous mutations. As a consequence attenuated viruses have only a few mutations responsible for the loss of virulence, which will differ between vaccines affecting virulence and/or immunogenicity and can revert to virulence. A new generation of vaccines is called for and one means of controlling IBV involves the development of new and safer vaccines by precisely modifying the IBV genome using reverse genetics for the production of rationally attenuated IBVs in order to obtain an optimum balance between loss of virulence and capacity to induce immunity.",,"['Britton, Paul', 'Armesto, Maria', 'Cavanagh, David', 'Keep, Sarah']",,,,
,PMC,Southeastern Center for Emerging Biologic Threats Tabletop Exercise: Foodborne Toxoplasmosis Outbreak on College Campuses,http://dx.doi.org/10.1089/bsp.2011.0040,PMC3316480,,,"The use of tabletop exercises as a tool in emergency preparedness and response has proven to be an effective means of assessing readiness for unexpected events. Whereas most exercise developers target a population in a defined space (eg, state, county, metropolitan area, hospital), the Southeastern Center for Emerging Biologic Threats (SECEBT) conducted an innovative tabletop exercise involving an unusual foodborne outbreak pathogen, targeting public health agencies and academic institutions in 7 southeastern states. The exercise tested the ability of participants to respond to a simulated foodborne disease outbreak affecting the region. The attendees represented 4 federal agencies, 9 state agencies, 6 universities, 1 nonprofit organization, and 1 private corporation. The goals were to promote collaborative relationships among the players, identify gaps in plans and policies, and identify the unique contributions of each organization—and notably academic institutions—to outbreak recognition, investigation, and control. Participants discussed issues and roles related to outbreak detection and management, risk communication, and coordination of policies and responsibilities before, during, and after an emergency, with emphasis on assets of universities that could be mobilized during an outbreak response. The exercise generated several lessons and recommendations identified by participants and evaluators. Key recommendations included a need to establish trigger points and protocols for information sharing and alerts among public health, academic, and law enforcement; to establish relationships with local, state, and federal stakeholders to facilitate communications during an emergency; and to catalogue and leverage strengths, assets, and priorities of academic institutions to add value to outbreak responses.",,"['Morris, J. Glenn', 'Greenspan, Allison', 'Howell, Kelly', 'Gargano, Lisa M.', 'Mitchell, Joanne', 'Jones, Jeffrey L.', 'Potter, Morris', 'Isakov, Alexander', 'Woods, Christopher', 'Hughes, James M.']",,,,
,PMC,Adult stem cells underlying lung regeneration,http://dx.doi.org/10.4161/cc.11.5.19328,PMC3323794,,,"Despite the massive toll in human suffering imparted by degenerative lung disease, including COPD, idiopathic pulmonary fibrosis and ARDS, the scientific community has been surprisingly agnostic regarding the potential of lung tissue and, in particular, the alveoli, to regenerate. However, there is circumstantial evidence in humans and direct evidence in mice that ARDS triggers robust regeneration of lung tissue rather than irreversible fibrosis. The stem cells responsible for this remarkable regenerative process has garnered tremendous attention, most recently yielding a defined set of cloned human airway stem cells marked by p63 expression but with distinct commitment to differentiated cell types typical of the upper or lower airways, the latter of which include alveoli-like structures in vitro and in vivo. These recent advances in lung regeneration and distal airway stem cells and the potential of associated soluble factors in regeneration must be harnessed for therapeutic options in chronic lung disease.",,"['Xian, Wa', 'McKeon, Frank']",,,,
,PMC,Targeting frameshifting in the human immunodeficiency virus,http://dx.doi.org/10.1517/14728222.2012.665879,PMC3328590,,,"INTRODUCTION: HIV-1 uses a programmed -1 ribosomal frameshift to generate Gag-Pol, the precursor of its enzymes, when its full-length mRNA is translated by the ribosomes of the infected cells. This change in the reading frame occurs at a so-called slippery sequence that is followed by a specific secondary structure, the frameshift stimulatory signal. This signal controls the frameshift efficiency. The synthesis of HIV-1 enzymes is critical for the virus replication and therefore, the -1 ribosomal frameshift could be the target of novel antiviral drugs. AREAS COVERED: This review examines various approaches used to select drugs interfering with the -1 frameshift of HIV-1. These include the selection and modification of chemical compounds that specifically bind to the frameshift stimulatory signal, the use of antisense oligonucleotides targeting this signal and the selection of compounds that modulate HIV-1 frameshift, by using bicistronic reporters where the expression of the second cistron depends upon HIV-1 frameshift. EXPERT OPINION: The most promising approach is the selection and modification of compounds specifically targeting HIV-1 frameshift stimulatory signal. The use of antisense oligonucleotides binding to the frameshift stimulatory signal is still questionable. The use of bicistronic reporters preferentially selects compounds that modulate the frameshift by targeting the ribosomes, which is less promising.",,"['Brakier-Gingras, Léa', 'Charbonneau, Johanie', 'Butcher, Samuel E.']",,,,
,PMC,From superspreaders to disease hotspots: linking transmission across hosts and space,http://dx.doi.org/10.1890/110111,PMC3589764,,,"Since the identification and imprisonment of “Typhoid Mary,” a woman who infected at least 47 people with typhoid in the early 1900s, epidemiologists have recognized that ‘superspreading’ hosts play a key role in disease epidemics. Such variability in transmission also exists among species within a community (amplification hosts) and among habitat patches across a landscape (disease ‘hotspots’), underscoring the need for an integrative framework for studying transmission heterogeneity. Here, we synthesize literature on human, plant, and animal diseases to evaluate the relative contributions of host, pathogen, and environmental factors in driving transmission heterogeneity across hosts and space. We show that host and spatial heterogeneity are closely linked and that quantitatively assessing the contribution of infectious individuals, species, or environmental patches to overall transmission can aid management strategies. We conclude by posing hypotheses regarding how pathogen natural history influences transmission heterogeneity and highlight emerging frontiers in the study of transmission heterogeneity.",,"['Paull, Sara H.', 'Song, Sejin', 'McClure, Katherine M.', 'Sackett, Loren C.', 'Kilpatrick, A. Marm', 'Johnson, Pieter T. J.']",,,,
,PMC,The Role of Distress in Uptake and Response to Predisposition Genetic Testing: The BMPR2 Experience,http://dx.doi.org/10.1089/gtmb.2011.0059,PMC3306587,,,"This study examines psychological determinants and effects of participating in genetic testing among persons diagnosed with or at risk for developing primary pulmonary arterial hypertension. Longitudinal data were drawn from orally administered surveys with 70 affected or at-risk individuals concerning their thoughts, feelings, and decision making about testing for mutations in BMPR2. Distress was measured by use of the Impact of Events Scale. Variations in tolerance for ambiguity were also examined. Although uptake of testing was low, as is common for incompletely penetrant mutations that lack clear therapeutic interventions, we found that those who participated in testing evidenced greater reduction in distress compared to those who had not participated in testing, irrespective of test result. No differences in tolerance for ambiguity by testing status were found. Participation in genetic testing, irrespective of test results, may be particularly beneficial to individuals who may have genetic mutations and who are experiencing high levels of distress.",,"['Jones, Diana L.', 'Clayton, Ellen W.']",,,,
,PMC,Why and When Should We Use Public Deliberation?,http://dx.doi.org/10.1002/hast.27,PMC3645483,,,,,"['SOLOMON, STEPHANIE', 'ABELSON, JULIA']",,,,
,PMC,Phenotypic Modulation of the Virulent Bvg Phase Is Not Required for Pathogenesis and Transmission of Bordetella bronchiseptica in Swine,http://dx.doi.org/10.1128/IAI.06016-11,PMC3294661,,,"The majority of virulence gene expression in Bordetella is regulated by a two-component sensory transduction system encoded by the bvg locus. In response to environmental cues, the BvgAS regulatory system controls expression of a spectrum of phenotypic phases, transitioning between a virulent (Bvg(+)) phase and a nonvirulent (Bvg(−)) phase, a process referred to as phenotypic modulation. We hypothesized that the ability of Bordetella bronchiseptica to undergo phenotypic modulation is required at one or more points during the infectious cycle in swine. To investigate the Bvg phase-dependent contribution to pathogenesis of B. bronchiseptica in swine, we constructed a series of isogenic mutants in a virulent B. bronchiseptica swine isolate and compared each mutant to the wild-type isolate for its ability to colonize and cause disease. We additionally tested whether a BvgAS system capable of modulation is required for direct or indirect transmission. The Bvg(−) phase-locked mutant was never recovered from any respiratory tract site at any time point examined. An intermediate phase-locked mutant (Bvg(i)) was found in numbers lower than the wild type at all respiratory tract sites and time points examined and caused limited to no disease. In contrast, colonization of the respiratory tract and disease caused by the Bvg(+) phase-locked mutant and the wild-type strain were indistinguishable. The Bvg(+) phase-locked mutant transmitted to naïve pigs by both direct and indirect contact with efficiency equal to that of the wild-type isolate. These results indicate that while full activation of the BvgAS regulatory system is required for colonization and severe disease, it is not deleterious to direct and indirect transmission. Overall, our results demonstrate that the Bvg(+) phase is sufficient for respiratory infection and host-to-host transmission of B. bronchiseptica in swine.",,"['Nicholson, Tracy L.', 'Brockmeier, Susan L.', 'Loving, Crystal L.', 'Register, Karen B.', 'Kehrli, Marcus E.', 'Stibitz, Scott E.', 'Shore, Sarah M.']",,,,
,PMC,Enteric Disease in Dogs Naturally Infected by a Novel Canine Astrovirus,http://dx.doi.org/10.1128/JCM.05018-11,PMC3295184,,,"Infection by a novel canine astrovirus was associated with gastroenteritis in two dogs. The virus displayed 70.3 to 73.9% amino acid identity to other canine astroviruses in the full-length capsid. Specific antibodies were detected in the convalescent-phase sera of the dogs, indicating seroconversion. Also, the virus appeared weakly related antigenically to the prototype canine astrovirus isolate ITA/2008/Bari.",,"['Martella, V.', 'Moschidou, P.', 'Catella, C.', 'Larocca, V.', 'Pinto, P.', 'Losurdo, M.', 'Corrente, M.', 'Lorusso, E.', 'Bànyai, K.', 'Decaro, N.', 'Lavazza, A.', 'Buonavoglia, C.']",,,,
,PMC,Severity of Human Rhinovirus Infection in Immunocompromised Adults Is Similar to That of 2009 H1N1 Influenza,http://dx.doi.org/10.1128/JCM.06579-11,PMC3295181,,,"This retrospective chart review of patients at a tertiary referral center compares characteristics and clinical features of patients diagnosed with human rhinovirus (HRV) infection to those of patients with 2009 H1N1 influenza A (pH1N1) during the pandemic respiratory season of 2009 to 2010. Hospital admission rates, intensive care unit (ICU) admissions, and mortality were not statistically different between the HRV and pH1N1 groups; however, more patients in the HRV group were considered immunocompromised.",,"['Kraft, Colleen S.', 'Jacob, Jesse T.', 'Sears, Marti H.', 'Burd, Eileen M.', 'Caliendo, Angela M.', 'Lyon, G. Marshall']",,,,
,PMC,Pooling Nasopharyngeal/Throat Swab Specimens To Increase Testing Capacity for Influenza Viruses by PCR,http://dx.doi.org/10.1128/JCM.05631-11,PMC3295167,,,"Real-time PCR methodology can be applied to rapidly and accurately detect influenza viruses. During times of surge testing or enhanced pandemic surveillance, public health laboratories (PHLs) may experience overwhelming demand for testing, even while the prevalence of positive specimens remains low. To improve laboratory capacity and testing efficiency during surges, we evaluated whether nasopharyngeal (NP)/throat swab specimens can be pooled and tested for the presence of the 2009 H1N1 influenza virus without a reduction in sensitivity. Pools of 10 specimens were extracted and concentrated upon elution on the MagNA Pure LC instrument, and real-time PCR was performed on the Applied Biosystems 7500 Fast platform, using the CDC swine influenza virus real-time RT-PCR detection panel (rRT-PCR swine flu panel). Specimens in positive pools were singly re-extracted and retested by PCR to identify individual positive samples. Initial studies showed that spiking a pool of nine negative specimens (100 μl each) or 900 μl of virus transport medium with 100 μl of a positive clinical specimen caused no loss of sensitivity by rRT-PCR testing. Pools containing either multiple positive specimens or specimens positive for other respiratory viruses also showed no negative effect on crossing threshold (C(T)) values. To test the robustness of the pooling protocol, a panel of 50 blinded samples was sent to three PHLs and tested in five pools of 10. All PHLs correctly identified the positive specimens. This study demonstrates the feasibility of using a pooling strategy to increase capacity and conserve resources during surge testing and periods of enhanced influenza surveillance when the prevalence is low.",,"['Van, Tam T.', 'Miller, Joseph', 'Warshauer, David M.', 'Reisdorf, Erik', 'Jernigan, Daniel', 'Humes, Rosemary', 'Shult, Peter A.']",,,,
,PMC,Performance of Different Mono- and Multiplex Nucleic Acid Amplification Tests on a Multipathogen External Quality Assessment Panel,http://dx.doi.org/10.1128/JCM.00200-11,PMC3295136,,,"An external quality assessment (EQA) panel consisting of a total of 48 samples in bronchoalveolar lavage (BAL) fluid or transport medium was prepared in collaboration with Quality Control for Molecular Diagnostics (QCMD) (www.qcmd.org). The panel was used to assess the proficiency of the three laboratories that would be responsible for examining the 6,000 samples to be collected in the GRACE Network of Excellence (www.grace-lrti.org). The main objective was to decide on the best-performing testing approach for the detection of influenza viruses A and B, parainfluenza virus types 1 to 3, respiratory syncytial virus (RSV), human metapneumovirus, coronavirus, rhinovirus, adenovirus, Chlamydophila pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila by nucleic acid amplification techniques (NAATs). Two approaches were chosen: (i) laboratories testing samples using their in-house procedures for extraction and amplification and (ii) laboratories using their in-house amplification procedures on centrally extracted samples. Furthermore, three commercially available multiplex NAAT tests—the ResPlex (Qiagen GmbH, Hilden, Germany), RespiFinder plus (PathoFinder, Maastricht, The Netherlands), and RespiFinder Smart 21 (PathoFinder) tests—were evaluated by examination of the same EQA panel by the manufacturer. No large differences among the 3 laboratories were noticed when the performances of the assays developed in-house in combination with the in-house extraction procedures were compared. Also, the extraction procedure (central versus local) had little effect on performance. However, large differences in amplification efficacy were found between the commercially available tests; acceptable results were obtained by using the PathoFinder assays.",,"['Loens, K.', 'van Loon, A. M.', 'Coenjaerts, F.', 'van Aarle, Y.', 'Goossens, H.', 'Wallace, P.', 'Claas, E. J. C.', 'Ieven, M.']",,,,
,PMC,"Evaluation of Swabs, Transport Media, and Specimen Transport Conditions for Optimal Detection of Viruses by PCR",http://dx.doi.org/10.1128/JCM.06551-11,PMC3295134,,,"Depletion of swabs and viral transport medium during epidemics may prompt the use of unvalidated alternatives. Swabs collected and transported dry or in saline were compared to commercially available swab/medium combinations for PCR detection of influenza, enterovirus, herpes simplex virus, and adenovirus. Each was detected at an ambient temperature (22°C) and 4°C for 7 days. Detection of influenza on dry or saline swabs is important because of its capacity to cause outbreaks involving large numbers of cases.",,"['Druce, Julian', 'Garcia, Katherine', 'Tran, Thomas', 'Papadakis, Georgina', 'Birch, Chris']",,,,
,PMC,Rapid Detection of the Marek's Disease Viral Genome in Chicken Feathers by Loop-Mediated Isothermal Amplification,http://dx.doi.org/10.1128/JCM.05408-11,PMC3295103,,,"A loop-mediated isothermal amplification (LAMP) method for the rapid detection of serotype 1 Marek's disease virus (MDV) was developed. The method used a set of three pairs of primers to amplify the MEQ gene for detecting serotype 1 MDV. The MDV LAMP method did not cross-react with serotype 2 and serotype 3, nor did the LAMP primers have binding sites for the common avian DNA viruses (reticuloendotheliosis virus, chicken anemia virus, subgroup J of the avian leukosis virus). Additionally, the assay could detect up to 10 copies of the MEQ gene in the MD viral genome, and it had 10 times higher sensitivity than the traditional PCR methods. The LAMP master mix was stable for 90 days at −20°C. Furthermore, the efficiency of LAMP for detection of serotype 1 MDV in clinical samples was comparable to those of PCR and viral isolation. The LAMP procedure is simple and does not rely on any special equipment. The detection of serotype 1 MDV by LAMP will be useful for detecting and controlling oncogenic Marek's disease.",,"['Angamuthu, Raja', 'Baskaran, Subasty', 'Gopal, Dhinakar Raj', 'Devarajan, Jeyanthi', 'Kathaperumal, Kumanan']",,,,
,PMC,Infection of human alveolar macrophages by human coronavirus strain 229E,http://dx.doi.org/10.1099/vir.0.038414-0,PMC3352353,,,"Human coronavirus strain 229E (HCoV-229E) commonly causes upper respiratory tract infections. However, lower respiratory tract infections can occur in some individuals, indicating that cells in the distal lung are susceptible to HCoV-229E. This study determined the virus susceptibility of primary cultures of human alveolar epithelial cells and alveolar macrophages (AMs). Fluorescent antibody staining indicated that HCoV-229E could readily infect AMs, but no evidence was found for infection in differentiated alveolar epithelial type II cells and only a very low level of infection in type II cells transitioning to the type I-like cell phenotype. However, a human bronchial epithelial cell line (16HBE) was readily infected. The innate immune response of AMs to HCoV-229E infection was evaluated for cytokine production and interferon (IFN) gene expression. AMs secreted significant amounts of tumour necrosis factor alpha (TNF-α), regulated on activation normal T-cell expressed and secreted (RANTES/CCL5) and macrophage inflammatory protein 1β (MIP-1β/CCL4) in response to HCoV-229E infection, but these cells exhibited no detectable increase in IFN-β or interleukin-29 in mRNA levels. AMs from smokers had reduced secretion of TNF-α compared with non-smokers in response to HCoV-229E infection. Surfactant protein A (SP-A) and SP-D are part of the innate immune system in the distal lung. Both surfactant proteins bound to HCoV-229E, and pre-treatment of HCoV-229E with SP-A or SP-D inhibited infection of 16HBE cells. In contrast, there was a modest reduction in infection in AMs by SP-A, but not by SP-D. In summary, AMs are an important target for HCoV-229E, and they can mount a pro-inflammatory innate immune response to infection.",,"['Funk, C. Joel', 'Wang, Jieru', 'Ito, Yoko', 'Travanty, Emily A.', 'Voelker, Dennis R.', 'Holmes, Kathryn V.', 'Mason, Robert J.']",,,,
,PMC,Rubella virus-like replicon particles: analysis of encapsidation determinants and non-structural roles of capsid protein in early post-entry replication,http://dx.doi.org/10.1099/vir.0.038984-0,PMC3352351,,,"Rubella virus (RUBV) contains a plus-strand RNA genome with two ORFs, one encoding the non-structural replicase proteins (NS-ORF) and the second encoding the virion structural proteins (SP-ORF). This study describes development and use of a trans-encapsidation system for the assembly of infectious RUBV-like replicon particles (VRPs) containing RUBV replicons (self replicating genomes with the SP-ORF replaced with a reporter gene). First, this system was used to map signals within the RUBV genome that mediate packaging of viral RNA. Mutations within a proposed packaging signal did not significantly affect relative packaging efficiency. The insertion of various fragments derived from the RUBV genome into Sindbis virus replicons revealed that there are several regions within the RUBV genome capable of enhancing encapsidation of heterologous replicon RNAs. Secondly, the trans-encapsidation system was used to analyse the effect of alterations within the capsid protein (CP) on release of VRPs and subsequent initiation of replication in newly infected cells. Deletion of the N-terminal eight amino acids of the CP reduced VRP titre significantly, which could be partially complemented by native CP provided in trans, indicating that this mutation affected an entry or post-entry event in the replication cycle. To test this hypothesis, the trans-encapsidation system was used to demonstrate the rescue of a lethal deletion within P150, one of the virus replicase proteins, by CP contained within the virus particle. This novel finding substantiated the functional role of CP in early post-entry replication.",,"['Claus, Claudia', 'Tzeng, Wen-Pin', 'Liebert, U. G', 'Frey, Teryl K.']",,,,
,PMC,Complete Genome Sequence of a Porcine Epidemic Diarrhea Virus Variant,http://dx.doi.org/10.1128/JVI.07150-11,PMC3302349,,,"In 2011, outbreaks of viral diarrhea were observed on most swine-breeding farms in most of the provinces of China. The disease is characterized by vomiting, severe diarrhea, and a high mortality rate (82.3%) in newborn piglets. The clinical appearance was similar to that of porcine epidemic diarrhea virus (PEDV) infection. PEDVs were detected in samples (feces or small intestines) from most farms. In order to investigate whether there is a PEDV variant circulating in China, we sequenced and analyzed the complete genome of the recently identified field strain, CH/FJND-3/2011. The sequence data indicate that this PEDV variant prevails in China.",,"['Chen, Jianfei', 'Liu, Xiaozhen', 'Shi, Da', 'Shi, Hongyan', 'Zhang, Xin', 'Feng, Li']",,,,
,PMC,Mutating Conserved Cysteines in the Alphavirus E2 Glycoprotein Causes Virus-Specific Assembly Defects,http://dx.doi.org/10.1128/JVI.06615-11,PMC3302346,,,"There are 80 trimeric, glycoprotein spikes that cover the surface of an alphavirus particle. The spikes, which are composed of three E2 and E1 glycoprotein heterodimers, are responsible for receptor binding and mediating fusion between the viral and host-cell membranes during entry. In addition, the cytoplasmic domain of E2 interacts with the nucleocapsid core during the last stages of particle assembly, possibly to aid in particle stability. During assembly, the spikes are nonfusogenic until the E3 glycoprotein is cleaved from E2 in the trans-Golgi network. Thus, a mutation in E2 potentially has effects on virus entry, spike assembly, or spike maturation. E2 is a highly conserved, cysteine-rich transmembrane glycoprotein. We made single cysteine-to-serine mutations within two distinct regions of the E2 ectodomain in both Sindbis virus and Ross River virus. Each of the E2 Cys mutants produced fewer infectious particles than wild-type virus. Further characterization of the mutant viruses revealed differences in particle morphology, fusion activity, and polyprotein cleavage between Sindbis and Ross River virus mutants, despite the mutations being made at corresponding positions in E2. The nonconserved assembly defects suggest that E2 folding and function is species dependent, possibly due to interactions with a virus-specific chaperone.",,"['Snyder, Anthony J.', 'Sokoloski, Kevin J.', 'Mukhopadhyay, Suchetana']",,,,
,PMC,A Human Antibody Recognizing a Conserved Epitope of H5 Hemagglutinin Broadly Neutralizes Highly Pathogenic Avian Influenza H5N1 Viruses,http://dx.doi.org/10.1128/JVI.06665-11,PMC3302345,,,"Influenza A virus infection is a persistent threat to public health worldwide due to its ability to evade immune surveillance through rapid genetic drift and shift. Current vaccines against influenza A virus provide immunity to viral isolates that are similar to vaccine strains. High-affinity neutralizing antibodies against conserved epitopes could provide immunity to diverse influenza virus strains and protection against future pandemic viruses. In this study, by using a highly sensitive H5N1 pseudotype-based neutralization assay to screen human monoclonal antibodies produced by memory B cells from an H5N1-infected individual and molecular cloning techniques, we developed three fully human monoclonal antibodies. Among them, antibody 65C6 exhibited potent neutralization activity against all H5 clades and subclades except for subclade 7.2 and prophylactic and therapeutic efficacy against highly pathogenic avian influenza H5N1 viruses in mice. Studies on hemagglutinin (HA)-antibody complexes by electron microscopy and epitope mapping indicate that antibody 65C6 binds to a conformational epitope comprising amino acid residues at positions 118, 121, 161, 164, and 167 (according to mature H5 numbering) on the tip of the membrane-distal globular domain of HA. Thus, we conclude that antibody 65C6 recognizes a neutralization epitope in the globular head of HA that is conserved among almost all divergent H5N1 influenza stains.",,"['Hu, Hongxing', 'Voss, Jarrod', 'Zhang, Guoliang', 'Buchy, Philippi', 'Zuo, Teng', 'Wang, Lulan', 'Wang, Feng', 'Zhou, Fan', 'Wang, Guiqing', 'Tsai, Cheguo', 'Calder, Lesley', 'Gamblin, Steve J.', 'Zhang, Linqi', 'Deubel, Vincent', 'Zhou, Boping', 'Skehel, John J.', 'Zhou, Paul']",,,,
,PMC,Genome-Wide Networks of Amino Acid Covariances Are Common among Viruses,http://dx.doi.org/10.1128/JVI.06857-11,PMC3302335,,,"Coordinated variation among positions in amino acid sequence alignments can reveal genetic dependencies at noncontiguous positions, but methods to assess these interactions are incompletely developed. Previously, we found genome-wide networks of covarying residue positions in the hepatitis C virus genome (R. Aurora, M. J. Donlin, N. A. Cannon, and J. E. Tavis, J. Clin. Invest. 119:225–236, 2009). Here, we asked whether such networks are present in a diverse set of viruses and, if so, what they may imply about viral biology. Viral sequences were obtained for 16 viruses in 13 species from 9 families. The entire viral coding potential for each virus was aligned, all possible amino acid covariances were identified using the observed-minus-expected-squared algorithm at a false-discovery rate of ≤1%, and networks of covariances were assessed using standard methods. Covariances that spanned the viral coding potential were common in all viruses. In all cases, the covariances formed a single network that contained essentially all of the covariances. The hepatitis C virus networks had hub-and-spoke topologies, but all other networks had random topologies with an unusually large number of highly connected nodes. These results indicate that genome-wide networks of genetic associations and the coordinated evolution they imply are very common in viral genomes, that the networks rarely have the hub-and-spoke topology that dominates other biological networks, and that network topologies can vary substantially even within a given viral group. Five examples with hepatitis B virus and poliovirus are presented to illustrate how covariance network analysis can lead to inferences about viral biology.",,"['Donlin, Maureen J.', 'Szeto, Brandon', 'Gohara, David W.', 'Aurora, Rajeev', 'Tavis, John E.']",,,,
,PMC,Deep Sequencing Identifies Viral and Wasp Genes with Potential Roles in Replication of Microplitis demolitor Bracovirus,http://dx.doi.org/10.1128/JVI.06434-11,PMC3302316,,,"Viruses in the genus Bracovirus (BV) (Polydnaviridae) are symbionts of parasitoid wasps that specifically replicate in the ovaries of females. Recent analysis of expressed sequence tags from two wasp species, Cotesia congregata and Chelonus inanitus, identified transcripts related to 24 different nudivirus genes. These results together with other data strongly indicate that BVs evolved from a nudivirus ancestor. However, it remains unclear whether BV-carrying wasps contain other nudivirus-like genes and what types of wasp genes may also be required for BV replication. Microplitis demolitor carries Microplitis demolitor bracovirus (MdBV). Here we characterized MdBV replication and performed massively parallel sequencing of M. demolitor ovary transcripts. Our results indicated that MdBV replication begins in stage 2 pupae and continues in adults. Analysis of prereplication- and active-replication-stage ovary RNAs yielded 22 Gb of sequence that assembled into 66,425 transcripts. This breadth of sampling indicated that a large percentage of genes in the M. demolitor genome were sequenced. A total of 41 nudivirus-like transcripts were identified, of which a majority were highly expressed during MdBV replication. Our results also identified a suite of wasp genes that were highly expressed during MdBV replication. Among these products were several transcripts with conserved roles in regulating locus-specific DNA amplification by eukaryotes. Overall, our data set together with prior results likely identify the majority of nudivirus-related genes that are transcriptionally functional during BV replication. Our results also suggest that amplification of proviral DNAs for packaging into BV virions may depend upon the replication machinery of wasps.",,"['Burke, Gaelen R.', 'Strand, Michael R.']",,,,
,PMC,Sensing of RNA Viruses: a Review of Innate Immune Receptors Involved in Recognizing RNA Virus Invasion,http://dx.doi.org/10.1128/JVI.05738-11,PMC3302314,,,"Our knowledge regarding the contribution of the innate immune system in recognizing and subsequently initiating a host response to an invasion of RNA virus has been rapidly growing over the last decade. Descriptions of the receptors involved and the molecular mechanisms they employ to sense viral pathogen-associated molecular patterns have emerged in great detail. This review presents an overview of our current knowledge regarding the receptors used to detect RNA virus invasion, the molecular structures these receptors sense, and the involved downstream signaling pathways.",,"['Jensen, Søren', 'Thomsen, Allan Randrup']",,,,
,PMC,Postexposure Treatment with the Live-Attenuated Rabies Virus (RV) Vaccine TriGAS Triggers the Clearance of Wild-Type RV from the Central Nervous System (CNS) through the Rapid Induction of Genes Relevant to Adaptive Immunity in CNS Tissues,http://dx.doi.org/10.1128/JVI.06699-11,PMC3302305,,,"Postexposure treatment (PET) of wild-type rabies virus (RV)-infected mice with a live-attenuated triple-glycoprotein RV variant (TriGAS) promotes survival but does not prevent the pathogenic RV from invading and replicating in the brain. Successful PET is associated with the induction of a robust virus-neutralizing antibody response and clearance of the wild-type RV from brain tissues. Comparison of the transcriptomes of normal mouse brain with those of wild-type-RV-infected mice that had received either mock or TriGAS PET treatment revealed that many of the host genes activated in the mock-treated mice represent type I interferon (IFN) response genes. This indicates that RV infection induces an early type I IFN response that is unable to control the infection. In contrast, most of the activated genes in the brain of the RV-infected, TriGAS-treated mouse play a role in adaptive immunity, including the regulation of T cell activation, T cell differentiation, and the regulation of lymphocyte and mononuclear cell proliferation. These findings were confirmed by quantitative PCR (qPCR) array studies, which showed that 3 genes in particular, encoding chemokine ligand 3 (Ccl3), natural killer cell activator 2 (interleukin 12B [IL-12B]), and granzyme A (GzmA), were activated earlier and to a greater extent in the brains of RV-infected mice treated with TriGAS than in the brains of mock-treated mice. The activation of these genes, known to play key roles in the regulation of lymphocyte and mononuclear cell proliferation, is likely an important part of the mechanism by which TriGAS mediates its PET activity.",,"['Li, Jianwei', 'Ertel, Adam', 'Portocarrero, Carla', 'Barkhouse, Darryll A.', 'Dietzschold, Bernhard', 'Hooper, D. Craig', 'Faber, Milosz']",,,,
,PMC,Residues in the Hendra Virus Fusion Protein Transmembrane Domain Are Critical for Endocytic Recycling,http://dx.doi.org/10.1128/JVI.05826-11,PMC3302302,,,"Hendra virus is a highly pathogenic paramyxovirus classified as a biosafety level four agent. The fusion (F) protein of Hendra virus is critical for promoting viral entry and cell-to-cell fusion. To be fusogenically active, Hendra virus F must undergo endocytic recycling and cleavage by the endosomal/lysosomal protease cathepsin L, but the route of Hendra virus F following internalization and the recycling signals involved are poorly understood. We examined the intracellular distribution of Hendra virus F following endocytosis and showed that it is primarily present in Rab5- and Rab4-positive endosomal compartments, suggesting that cathepsin L cleavage occurs in early endosomes. Hendra virus F transmembrane domain (TMD) residues S490 and Y498 were found to be important for correct Hendra virus F recycling, with the hydroxyl group of S490 and the aromatic ring of Y498 important for this process. In addition, changes in association of isolated Hendra virus F TMDs correlated with alterations to Hendra virus F recycling, suggesting that appropriate TMD interactions play an important role in endocytic trafficking.",,"['Popa, Andreea', 'Carter, James R.', 'Smith, Stacy E.', 'Hellman, Lance', 'Fried, Michael G.', 'Dutch, Rebecca Ellis']",,,,
,PMC,Filoviruses Require Endosomal Cysteine Proteases for Entry but Exhibit Distinct Protease Preferences,http://dx.doi.org/10.1128/JVI.06346-11,PMC3302294,,,"Filoviruses are enveloped viruses that cause sporadic outbreaks of severe hemorrhagic fever [CDC, MMWR Morb. Mortal. Wkly. Rep. 50:73–77, 2001; Colebunders and Borchert, J. Infect. 40:16–20, 2000; Colebunders et al., J. Infect. Dis. 196(Suppl. 2):S148–S153, 2007; Geisbert and Jahrling, Nat. Med. 10:S110-S121, 2004]. Previous studies revealed that endosomal cysteine proteases are host factors for ebolavirus Zaire (Chandran et al., Science 308:1643–1645, 2005; Schornberg et al., J. Virol. 80:4174–4178, 2006). In this report, we show that infection mediated by glycoproteins from other phylogenetically diverse filoviruses are also dependent on these proteases and provide additional evidence indicating that they cleave GP1 and expose the binding domain for the critical host factor Niemann-Pick C1. Using selective inhibitors and knockout-derived cell lines, we show that the ebolaviruses Zaire and Cote d'Ivoire are strongly dependent on cathepsin B, while the ebolaviruses Sudan and Reston and Marburg virus are not. Taking advantage of previous studies of cathepsin B inhibitor-resistant viruses (Wong et al., J. Virol. 84:163–175, 2010), we found that virus-specific differences in the requirement for cathepsin B are correlated with sequence polymorphisms at residues 47 in GP1 and 584 in GP2. We applied these findings to the analysis of additional ebolavirus isolates and correctly predicted that the newly identified ebolavirus species Bundibugyo, containing D47 and I584, is cathepsin B dependent and that ebolavirus Zaire-1995, the single known isolate of ebolavirus Zaire that lacks D47, is not. We also obtained evidence for virus-specific differences in the role of cathepsin L, including cooperation with cathepsin B. These studies strongly suggest that the use of endosomal cysteine proteases as host factors for entry is a general property of members of the family Filoviridae.",,"['Misasi, John', 'Chandran, Kartik', 'Yang, Jin-Yi', 'Considine, Bryden', 'Filone, Claire Marie', 'Côté, Marceline', 'Sullivan, Nancy', 'Fabozzi, Giulia', 'Hensley, Lisa', 'Cunningham, James']",,,,
,PMC,Ultrastructural Characterization of Arterivirus Replication Structures: Reshaping the Endoplasmic Reticulum To Accommodate Viral RNA Synthesis,http://dx.doi.org/10.1128/JVI.06677-11,PMC3302280,,,"Virus-induced membrane structures support the assembly and function of positive-strand RNA virus replication complexes. The replicase proteins of arteriviruses are associated with double-membrane vesicles (DMVs), which were previously proposed to derive from the endoplasmic reticulum (ER). Using electron tomography, we performed an in-depth ultrastructural analysis of cells infected with the prototypic arterivirus equine arteritis virus (EAV). We established that the outer membranes of EAV-induced DMVs are interconnected with each other and with the ER, thus forming a reticulovesicular network (RVN) resembling that previously described for the distantly related severe acute respiratory syndrome (SARS) coronavirus. Despite significant morphological differences, a striking parallel between the two virus groups, and possibly all members of the order Nidovirales, is the accumulation in the DMV interior of double-stranded RNA, the presumed intermediate of viral RNA synthesis. In our electron tomograms, connections between the DMV interior and cytosol could not be unambiguously identified, suggesting that the double-stranded RNA is compartmentalized by the DMV membranes. As a novel approach to visualize and quantify the RNA content of viral replication structures, we explored electron spectroscopic imaging of DMVs, which revealed the presence of phosphorus in amounts equaling on average a few dozen copies of the EAV RNA genome. Finally, our electron tomograms revealed a network of nucleocapsid protein-containing protein tubules that appears to be intertwined with the RVN. This potential intermediate in nucleocapsid formation, which was not observed in coronavirus-infected cells, suggests that arterivirus RNA synthesis and assembly are coordinated in intracellular space.",,"['Knoops, Kèvin', 'Bárcena, Montserrat', 'Limpens, Ronald W. A. L.', 'Koster, Abraham J.', 'Mommaas, A. Mieke', 'Snijder, Eric J.']",,,,
,PMC,Infectious Spleen and Kidney Necrosis Virus (a Fish Iridovirus) Enters Mandarin Fish Fry Cells via Caveola-Dependent Endocytosis,http://dx.doi.org/10.1128/JVI.06947-11,PMC3302275,,,"Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus from the family Iridoviridae. Megalocytiviruses have been implicated in more than 50 fish species infections and currently threaten the aquaculture industry, causing great economic losses in China, Japan, and Southeast Asia. However, the cellular entry mechanisms of megalocytiviruses remain largely uncharacterized. In this study, the main internalization mechanism of ISKNV was investigated by using mandarin fish fry (MFF-1) cells. The progression of ISKNV infection is slow, and infection is not inhibited when the cells are treated with ammonium chloride (NH(4)Cl), chloroquine, sucrose, and chlorpromazine, which are inhibitors of clathrin-dependent endocytosis. The depletion of cellular cholesterol by methyl-β-cyclodextrin results in the significant inhibition of ISKNV infection; however, the infection is resumed with cholesterol replenishment. Inhibitors of caveolin-1-involved signaling events, including phorbol 12-myristate 13-acetate (PMA), genistein, and wortmannin, impair ISKNV entry into MFF-1 cells. Moreover, ISKNV entry is dependent on dynamin and the microtubule cytoskeleton. Cofraction analysis of ISKNV and caveolin-1 showed that ISKNV colocates with caveolin-1 during virus infection. These results indicate that ISKNV entry into MFF-1 cells proceeds via classical caveola-mediated endocytosis and is dependent on the microtubules that serve as tracks along which motile cavicles may move via a caveola-caveosome-endoplasmic reticulum (ER) pathway. As a fish iridovirus, ISKNV entry into MFF-1 cells is different from the clathrin-mediated endocytosis of frog virus 3 entry into mammalian cells (BHK-21) at 28°C, which has been recognized as a model for iridoviruses. Thus, our work may help further the understanding of the initial steps of iridovirus infection.",,"['Guo, Chang-Jun', 'Wu, Yan-Yan', 'Yang, Li-Shi', 'Yang, Xiao-Bo', 'He, Jian', 'Mi, Shu', 'Jia, Kun-Tong', 'Weng, Shao-Ping', 'Yu, Xiao-Qiang', 'He, Jian-Guo']",,,,
,PMC,"Coordinate Deletion of N-Glycans from the Heptad Repeats of the Fusion F Protein of Newcastle Disease Virus Yields a Hyperfusogenic Virus with Increased Replication, Virulence, and Immunogenicity",http://dx.doi.org/10.1128/JVI.06380-11,PMC3302274,,,"The role of N-linked glycosylation of the Newcastle disease virus (NDV) fusion (F) protein in viral replication and pathogenesis was examined by eliminating potential acceptor sites using a reverse genetics system for the moderately pathogenic strain Beaudette C (BC). The NDV-BC F protein contains six potential acceptor sites for N-linked glycosylation at residues 85, 191, 366, 447, 471, and 541 (sites Ng1 to Ng6, respectively). The sites at Ng2 and Ng5 are present in heptad repeat (HR) domains HR1 and HR2, respectively, and thus might affect fusion. Each N-glycosylation site was eliminated individually by replacing asparagine (N) with glutamine (Q), and a double mutant (Ng2 + 5) involving the two HR domains was also made. Each mutant was successfully recovered by reverse genetics except for the one involving Ng6, which is present in the cytoplasmic domain. All of the F proteins expressed by the recovered mutant viruses were efficiently cleaved and transported to the infected-cell surface. None of the individual mutations affected viral fusogenicity, but the double mutation at Ng2 and Ng5 in HR1 and HR2 increased fusogenicity >12-fold. The single mutations at sites Ng1, Ng2, and Ng5 resulted in modestly reduced multicycle growth in vitro. These three single mutations were also the most attenuating in eggs and 1-day-old chicks and were associated with decreased replication and spread in 2-week-old chickens. In contrast, the combination of the mutations at Ng2 and Ng5 yielded a virus that, compared to the BC parent, replicated >100-fold more efficiently in vitro, was more virulent in eggs and chicks, replicated more efficiently in chickens with enhanced tropism for the brain and gut, and elicited stronger humoral cell responses. These results illustrate the effects of N-glycosylation of the F protein on NDV pathobiology and suggest that the N-glycans in HR1 and HR2 coordinately downregulate viral fusion and virulence.",,"['Samal, Sweety', 'Khattar, Sunil K.', 'Kumar, Sachin', 'Collins, Peter L.', 'Samal, Siba K.']",,,,
,PMC,"Natural Occurrence and Characterization of Two Internal Ribosome Entry Site Elements in a Novel Virus, Canine Picodicistrovirus, in the Picornavirus-Like Superfamily",http://dx.doi.org/10.1128/JVI.05481-11,PMC3302267,,,"Dicistroviridae and Picornaviridae are two phylogenetically related families of positive-sense single-stranded RNA viruses in the picornavirus-like superfamily with similar gene contents but different genome organizations and hosts. In a surveillance study involving 1,472 samples from 368 dogs over a 22-month period, we identified a novel picornavirus-like virus from 47 fecal and urine samples by the use of reverse transcription-PCR (RT-PCR). Sequencing and phylogenetic analysis of three complete genomes revealed that, although it seemed that the virus was most closely related to other picornaviruses, P1, P2, and P3 of the virus possessed very low amino acid identities of <30% to those of all other known picornaviruses and that the amino acid identities between the 3D(pol) and 2C of the virus and the RNA-dependent RNA polymerases and helicases of all other picornaviruses were <35%. Distinct from other picornaviruses, the genomes of the virus contain two putative internal ribosome entry sites (IRESs) and two open reading frames, encoding two polyprotein precursors (844 and 1,406 amino acids), separated by an intergenic region (IGR) of 588 bases. A dual-luciferase activity assay using DNA and RNA transfection revealed that both IRESs were functional. Quantitative RT-PCR showed that numbers of viral RNAs ranged from 7.55 × 10(6) to 1.26 × 10(9) copies/ml of urine and 1.82 × 10(6) to 4.97 × 10(10) copies/ml of fecal sample. This is the first report of the natural occurrence of two functional IRESs in nondicistroviruses. Based on our results, we have proposed a novel species, canine picodicistrovirus (CPDV), to describe this novel member of the picornavirus-like superfamily, which could represent a novel family of viruses.",,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Choi, Garnet K. Y.', 'Huang, Yi', 'Teng, Jade L. L.', 'Tsoi, Hoi-Wah', 'Tse, Herman', 'Yeung, Man Lung', 'Chan, Kwok-Hung', 'Jin, Dong-Yan', 'Yuen, Kwok-Yung']",,,,
,PMC,CD4 T Cells Promote CD8 T Cell Immunity at the Priming and Effector Site during Viral Encephalitis,http://dx.doi.org/10.1128/JVI.06797-11,PMC3302259,,,"CD4 T cell activation during peripheral infections not only is essential in inducing protective CD8 T cell memory but also promotes CD8 T cell function and survival. However, the contributions of CD4 T cell help to antiviral CD8 T cell immunity during central nervous system (CNS) infection are not well established. Encephalitis induced by the sublethal coronavirus JHMV was used to identify when CD4 T cells regulate CD8 T cell responses following CNS infection. Peripheral expansion of virus-specific CD8 T cells was impaired when CD4 T cells were ablated prior to infection but not at 4 days postinfection. Delayed CD4 T cell depletion abrogated CD4 T cell recruitment to the CNS but only slightly diminished CD8 T cell recruitment. Nevertheless, the absence of CNS CD4 T cells was associated with reduced gamma interferon (IFN-γ) and granzyme B expression by infiltrating CD8 T cells, increased CD8 T cell apoptosis, and impaired control of infectious virus. CD4 T cell depletion subsequent to CD4 T cell CNS migration restored CD8 T cell activity and virus control. Analysis of γc-dependent cytokine expression indicated interleukin-21 (IL-21) as a primary candidate optimizing CD8 T cell activity within the CNS. These results demonstrate that CD4 T cells play critical roles in both enhancing peripheral activation of CD8 T cells and prolonging their antiviral function within the CNS. The data highlight the necessity for temporally and spatially distinct CD4 T cell helper functions in sustaining CD8 T cell activity during CNS infection.",,"['Phares, Timothy W.', 'Stohlman, Stephen A.', 'Hwang, Mihyun', 'Min, Booki', 'Hinton, David R.', 'Bergmann, Cornelia C.']",,,,
,PMC,Evidence for a Common Evolutionary Origin of Coronavirus Spike Protein Receptor-Binding Subunits,http://dx.doi.org/10.1128/JVI.06882-11,PMC3302248,,,"Among different coronavirus genera, the receptor-binding S1 subunits of their spike proteins differ in primary, secondary, and tertiary structures. This study identified shared structural topologies (connectivity of secondary structural elements) in S1 domains of different coronavirus genera. The results suggest that coronavirus S1 subunits share a common evolutionary origin but have attained diverse sequences and structures following extensive divergent evolution. The results also increase understanding of the structures and functions of coronavirus S1 domains whose tertiary structures are currently unknown.",,"Li, Fang",,,,
,PMC,Into the Eye of the Cytokine Storm,http://dx.doi.org/10.1128/MMBR.05015-11,PMC3294426,,,"Summary: The cytokine storm has captured the attention of the public and the scientific community alike, and while the general notion of an excessive or uncontrolled release of proinflammatory cytokines is well known, the concept of a cytokine storm and the biological consequences of cytokine overproduction are not clearly defined. Cytokine storms are associated with a wide variety of infectious and noninfectious diseases. The term was popularized largely in the context of avian H5N1 influenza virus infection, bringing the term into popular media. In this review, we focus on the cytokine storm in the context of virus infection, and we highlight how high-throughput genomic methods are revealing the importance of the kinetics of cytokine gene expression and the remarkable degree of redundancy and overlap in cytokine signaling. We also address evidence for and against the role of the cytokine storm in the pathology of clinical and infectious disease and discuss why it has been so difficult to use knowledge of the cytokine storm and immunomodulatory therapies to improve the clinical outcomes for patients with severe acute infections.",,"['Tisoncik, Jennifer R.', 'Korth, Marcus J.', 'Simmons, Cameron P.', 'Farrar, Jeremy', 'Martin, Thomas R.', 'Katze, Michael G.']",,,,
,PMC,A Novel Feedback Loop Regulates the Response to Endoplasmic Reticulum Stress via the Cooperation of Cytoplasmic Splicing and mRNA Translation,http://dx.doi.org/10.1128/MCB.06665-11,PMC3295193,,,"The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers transcriptional and translational reprogramming. This unfolded protein response (UPR) protects cells during transient stress and can lead to apoptosis during prolonged stress. Two key mediators of the UPR are PKR-like ER kinase (PERK), which phosphorylates the α subunit of eukaryotic translation initiation factor 2 (eIF2α), resulting in decreased protein synthesis, and the α subunit of inositol-requiring enzyme 1 (IRE1α), which initiates cytoplasmic splicing of the mRNA encoding the transcription factor X-box binding protein 1 (XBP1). XBP1 induces transcription of genes involved in protein quality control. This report describes cross talk between these two pathways: phosphorylation of eIF2α was required for maximal induction of spliced XBP1 (XBP1s) protein levels via a mechanism that involved stabilization of XBP1s mRNA. By using mouse embryo fibroblasts deficient in UPR signaling pathways, we demonstrate that stress-induced stabilization of XBP1s mRNA requires cytoplasmic splicing of the mRNA and inhibition of its translation. Because the XBP1s protein promotes transcription of its own gene, the UPR-induced mRNA stabilization is part of a positive feedback loop that induces XBP1s protein accumulation and transcription of target genes during stress. We propose a model in which eIF2α phosphorylation-mediated control of mRNA turnover is a molecular switch that regulates the stress response transcription program and the ER's capacity for protein folding during stress.",,"['Majumder, Mithu', 'Huang, Charlie', 'Snider, Martin D.', 'Komar, Anton A.', 'Tanaka, Junichi', 'Kaufman, Randal J.', 'Krokowski, Dawid', 'Hatzoglou, Maria']",,,,
,PMC,Human Coronavirus in Young Children Hospitalized for Acute Respiratory Illness and Asymptomatic Controls,http://dx.doi.org/10.1097/INF.0b013e31823e07fe,PMC3288315,,,"BACKGROUND: Human coronaviruses (HCoVs) have been detected in children with upper and lower respiratory symptoms but little is known about their relationship with severe respiratory illness. OBJECTIVE: To compare the prevalence of HCoV species among children hospitalized for acute respiratory illness and/or fever with asymptomatic controls and to assess the severity of outcomes among hospitalized children with HCoV compared with other respiratory viruses. METHODS: From December 2003–April 2004 and October 2004–April 2005, we conducted prospective, population-based surveillance of children <5 years of age hospitalized for ARI/fever in three U.S. counties. Asymptomatic outpatient controls were enrolled concurrently. Nasal/throat swabs were tested for HCoV species HKU1, NL63, 229E, and OC43 by RT-PCR. Specimens from hospitalized children were also tested for other common respiratory viruses. Demographic and medical data were collected by parent/guardian interview and medical chart review. RESULTS: Overall, HCoV was detected in 113 (7.6%) of 1,481 hospitalized children (83 [5.7%] after excluding 30 cases coinfected with other viruses) and 53 (7.1%) of 742 controls. The prevalence of HCoV or individual species was not significantly higher among hospitalized children than controls. Hospitalized children testing positive for HCoV alone tended to be less ill than those infected with other viruses, while those coinfected with HCoV and other viruses were clinically similar to those infected with other viruses alone. CONCLUSION: In this study of children hospitalized for acute respiratory illness and/or fever, HCoV infection was not associated with hospitalization or with increased severity of illness.",,"['Prill, Mila M.', 'Iwane, Marika K.', 'Edwards, Kathryn M.', 'Williams, John V.', 'Weinberg, Geoffrey A.', 'Staat, Mary A.', 'Willby, Melisa J.', 'Talbot, H. Keipp', 'Hall, Caroline B.', 'Szilagyi, Peter G.', 'Griffin, Marie R.', 'Curns, Aaron T.', 'Erdman, Dean D.', None]",,,,
,PMC,Can Kawasaki Disease Be Managed?,,PMC3383169,,,"Kawasaki Disease (KD) is the leading cause of acquired cardiovascular disease among children, but management of KD has received relatively little attention. In the US alone, about 5500 cases were estimated in 2009. KD is most common among Asian and Pacific Islander children but can affect all ethnicities and races. Timely and accurate diagnosis remains critical, but difficult: the etiology of KD is unknown, and no accurate diagnostic laboratory test has been developed. Continuing medical education can help physicians, clinicians, and nurse practitioners accurately diagnose and treat KD. A registry specific to KD or a surveillance system may be necessary to increase awareness among health care professionals and to decrease complications related to misdiagnosis.",,"['Coustasse, Alberto', 'Larry, Julius', 'Lee, Doohee']",,,,
,PMC,The 5′ UTR of HIV-1 full-length mRNA and the Tat viral protein modulate the programmed −1 ribosomal frameshift that generates HIV-1 enzymes,http://dx.doi.org/10.1261/rna.030346.111,PMC3285939,,,"Translation of the full-length messenger RNA (mRNA) of the human immunodeficiency virus type 1 (HIV-1) generates the precursor of the viral enzymes via a programmed −1 ribosomal frameshift. Here, using dual-luciferase reporters, we investigated whether the highly structured 5′ untranslated region (UTR) of this mRNA, which interferes with translation initiation, can modulate HIV-1 frameshift efficiency. We showed that, when the 5′ UTR of HIV-1 mRNA occupies the 5′ end of the reporter mRNA, HIV-1 frameshift efficiency is increased about fourfold in Jurkat T-cells, compared with a control dual-luciferase reporter with a short unstructured 5′ UTR. This increase was related to an interference with cap-dependent translation initiation by the TAR-Poly(A) region at the 5′ end of the messenger. HIV-1 mRNA 5′ UTR also contains an internal ribosome entry site (IRES), but we showed that, when the cap-dependent initiation mode is available, the IRES is not used or is weakly used. However, when the ribosomes have to use the IRES to translate the dual-luciferase reporter, the frameshift efficiency is comparable to that of the control dual-luciferase reporter. The decrease in cap-dependent initiation and the accompanying increase in frameshift efficiency caused by the 5′ UTR of HIV-1 mRNA is antagonized, in a dose-dependent way, by the Tat viral protein. Tat also stimulates the IRES-dependent initiation and decreases the corresponding frameshift efficiency. A model is presented that accounts for the variations in frameshift efficiency depending on the 5′ UTR and the presence of Tat, and it is proposed that a range of frameshift efficiencies is compatible with the virus replication.",,"['Charbonneau, Johanie', 'Gendron, Karine', 'Ferbeyre, Gerardo', 'Brakier-Gingras, Léa']",,,,
,PMC,Productive Replication of Ebola Virus Is Regulated by the c-Abl1 Tyrosine Kinase,http://dx.doi.org/10.1126/scitranslmed.3003500,PMC4794994,,,"Ebola virus causes a fulminant infection in humans resulting in diffuse bleeding, vascular instability, hypotensive shock, and often death. Because of its high mortality and ease of transmission from human to human, Ebola virus remains a biological threat for which effective preventive and therapeutic interventions are needed. An understanding of the mechanisms of Ebola virus pathogenesis is critical for developing antiviral therapeutics. Here, we report that productive replication of Ebola virus is modulated by the c-Abl1 tyrosine kinase. Release of Ebola virus–like particles (VLPs) in a cell culture cotransfection system was inhibited by c-Abl1–specific small interfering RNA (siRNA) or by Abl-specific kinase inhibitors and required tyrosine phosphorylation of the Ebola matrix protein VP40. Expression of c-Abl1 stimulated an increase in phosphorylation of tyrosine 13 (Y(13)) of VP40, and mutation of Y(13) to alanine decreased the release of Ebola VLPs. Productive replication of the highly pathogenic Ebola virus Zaire strain was inhibited by c-Abl1–specific siRNAs or by the Abl-family inhibitor nilotinib by up to four orders of magnitude. These data indicate that c-Abl1 regulates budding or release of filoviruses through a mechanism involving phosphorylation of VP40. This step of the virus life cycle therefore may represent a target for antiviral therapy.",,"['García, Mayra', 'Cooper, Arik', 'Shi, Wei', 'Bornmann, William', 'Carrion, Ricardo', 'Kalman, Daniel', 'Nabel, Gary J.']",,,,
,PMC,Viruses and Interactomes in Translation,http://dx.doi.org/10.1074/mcp.M111.014738,PMC3394946,,,"A decade of high-throughput screenings for intraviral and virus-host protein-protein interactions led to the accumulation of data and to the development of theories on laws governing interactome organization for many viruses. We present here a computational analysis of intraviral protein networks (EBV, FLUAV, HCV, HSV-1, KSHV, SARS-CoV, VACV, and VZV) and virus-host protein networks (DENV, EBV, FLUAV, HCV, and VACV) from up-to-date interaction data, using various mathematical approaches. If intraviral networks seem to behave similarly, they are clearly different from the human interactome. Viral proteins target highly central human proteins, which are precisely the Achilles' heel of the human interactome. The intrinsic structural disorder is a distinctive feature of viral hubs in virus-host interactomes. Overlaps between virus-host data sets identify a core of human proteins involved in the cellular response to viral infection and in the viral capacity to hijack the cell machinery for viral replication. Host proteins that are strongly targeted by a virus seem to be particularly attractive for other viruses. Such protein-protein interaction networks and their analysis represent a powerful resource from a therapeutic perspective.",,"['Meyniel-Schicklin, Laurène', 'de Chassey, Benoît', 'André, Patrice', 'Lotteau, Vincent']",,,,
,PMC,A distinct lineage of influenza A virus from bats,http://dx.doi.org/10.1073/pnas.1116200109,PMC3306675,,,"Influenza A virus reservoirs in animals have provided novel genetic elements leading to the emergence of global pandemics in humans. Most influenza A viruses circulate in waterfowl, but those that infect mammalian hosts are thought to pose the greatest risk for zoonotic spread to humans and the generation of pandemic or panzootic viruses. We have identified an influenza A virus from little yellow-shouldered bats captured at two locations in Guatemala. It is significantly divergent from known influenza A viruses. The HA of the bat virus was estimated to have diverged at roughly the same time as the known subtypes of HA and was designated as H17. The neuraminidase (NA) gene is highly divergent from all known influenza NAs, and the internal genes from the bat virus diverged from those of known influenza A viruses before the estimated divergence of the known influenza A internal gene lineages. Attempts to propagate this virus in cell cultures and chicken embryos were unsuccessful, suggesting distinct requirements compared with known influenza viruses. Despite its divergence from known influenza A viruses, the bat virus is compatible for genetic exchange with human influenza viruses in human cells, suggesting the potential capability for reassortment and contributions to new pandemic or panzootic influenza A viruses.",,"['Tong, Suxiang', 'Li, Yan', 'Rivailler, Pierre', 'Conrardy, Christina', 'Castillo, Danilo A. Alvarez', 'Chen, Li-Mei', 'Recuenco, Sergio', 'Ellison, James A.', 'Davis, Charles T.', 'York, Ian A.', 'Turmelle, Amy S.', 'Moran, David', 'Rogers, Shannon', 'Shi, Mang', 'Tao, Ying', 'Weil, Michael R.', 'Tang, Kevin', 'Rowe, Lori A.', 'Sammons, Scott', 'Xu, Xiyan', 'Frace, Michael', 'Lindblade, Kim A.', 'Cox, Nancy J.', 'Anderson, Larry J.', 'Rupprecht, Charles E.', 'Donis, Ruben O.']",,,,
,PMC,Testing the relation between dispositional optimism and conditioned pain modulation: Does ethnicity matter?,http://dx.doi.org/10.1007/s10865-012-9411-7,PMC3605222,,,"Greater dispositional optimism has been related to less severe pain; however, whether optimism is associated with endogenous pain modulation has not yet been examined. The beneficial effects of dispositional optimism often vary according to cultural dynamics. Thus, assessing optimism-pain relationships across different ethnic groups is warranted. This study sought to examine the association between optimism and conditioned pain modulation (CPM), and test whether this association differs according to ethnicity. Optimism and CPM were assessed in a sample of healthy, ethnically diverse young adults. CPM was determined by comparing pressure pain thresholds obtained before and during exposure to a cold pressor task. All participants completed a validated measure of dispositional optimism. Greater reported optimism was significantly associated with enhanced CPM, and the strength of this association did not vary according to individuals’ ethnic background. These findings suggest that an optimistic disposition may potentiate endogenous pain inhibition.",,"['Goodin, Burel R.', 'Kronfli, Tarek', 'King, Christopher D.', 'Glover, Toni L.', 'Sibille, Kimberly', 'Fillingim, Roger B.']",,,,
,PMC,A Network-based Analysis of the 1861 Hagelloch Measles Data,http://dx.doi.org/10.1111/j.1541-0420.2012.01748.x,PMC4553425,,,"In this article, we demonstrate a statistical method for fitting the parameters of a sophisticated network and epidemic model to disease data. The pattern of contacts between hosts is described by a class of dyadic independence Exponential-family Random Graph Models (ERGMs) while the transmission process that runs over the network is modeled as a stochastic Susceptible-Exposed-Infectious-Removed (SEIR) epidemic. We fit these models to very detailed data from the 1861 measles outbreak in Hagelloch, Germany. The network models include parameters for all recorded host covariates including age, sex, household and classroom membership and household location while the SEIR epidemic model has exponentially distributed transmission times with gamma distributed latent and infective periods. This approach allows us to make meaningful statements about the structure of the population—separate from the transmission process—as well as to provide estimates of various biological quantities of interest, such as the effective reproductive number, R. Using reversible jump Markov chain Monte Carlo, we produce samples from the joint posterior distribution of all the parameters of this model—the network, transmission tree, network parameters and SEIR parameters—and perform Bayesian model selection to find the best-fitting network model. We compare our results with those of previous analyses and show that the ERGM network model better fits the data than a Bernoulli network model previously used. We also provide a software package, written in R, that performs this type of analysis.",,"['Groendyke, Chris', 'Welch, David', 'Hunter, David R.']",,,,
,PMC,Correction: The Murine Coronavirus Hemagglutinin-esterase Receptor-binding Site: A Major Shift in Ligand Specificity through Modest Changes in Architecture,http://dx.doi.org/10.1371/annotation/a1e2a2e4-df03-40db-b10b-fd0cfcf78d3c,PMC3284578,,CC BY,,2012 Feb 22,"['Langereis, Martijn A.', 'Zeng, Qinghong', 'Heesters, Balthasar A.', 'Huizinga, Eric G.', 'de Groot, Raoul J.']",PLoS Pathog,,,
,PMC,Galectin-1 triggers an immunoregulatory signature in T helper cells functionally defined by IL-10 expression,http://dx.doi.org/10.4049/jimmunol.1103433,PMC3311782,,,"Galectin-1 (Gal-1), aβ-galactoside-binding protein, can alter fate and effector function of T helper (Th) cells; however, little is known about how Gal-1 induces Th cell differentiation. Here, we show that both uncommitted and polarized Th cells bound by Gal-1 expressed an immunoregulatory signature defined by IL-10. IL-10synthesis was stimulated by direct Gal-1 engagement to cell surface glycoproteins, principally CD45, on activated Th cells and enhanced by IL-21 expression through the c-Maf/aryl hydrocarbon receptor (AhR) pathway, independent of antigen-presenting cells. Gal-1-induced IL-10(+) Tcells efficiently suppressed T cell proliferation and T-cell-mediated inflammation and promoted the establishment of cancer immune-privileged sites. Collectively, these findings show how Gal-1 functions as a major glycome determinant regulating Th cell development, inflammation and tumor immunity.",,"['Cedeno-Laurent, Filiberto', 'Opperman, Matthew', 'Barthel, Steven R.', 'Kuchroo, Vijay K.', 'Dimitroff, Charles J.']",,,,
,PMC,Vaccine Candidates PhtD and PhtE of Streptococcus pneumoniae are adhesins that elicit functional antibodies in humans,http://dx.doi.org/10.1016/j.vaccine.2012.02.023,PMC3490617,,,"We evaluated the role of vaccine candidate surface proteins, PhtD and PhtE as antigens with functional importance for Streptococcus pneumoniae (pneumococci) in adherence to nasopharyngeal (D562) and lung (A549) epithelial cell lines. Comparing TIGR4 to PhtD and PhtE-deleted isogenic mutants, a 40% (p=0.001) and 42% (p=0.002) drop in the number of epithelial cells with adherent pneumococci was observed to both cells lines with the mutants, as quantitated using flow cytometry. We expressed PhtD and PhtE on the surface of E coli and demonstrated that when PhtD and PhtE were surface expressed on E coli adherence increased to D562 and A549 cells, compared with the E coli parent strain (p = 0.005, 0.013 for D562 and p=0.034, p=0.035 for A549). Using flow cytometry and confocal microscopy we found that pneumococci aggregated in the presence of human serum IgG, leading to a non-specific drop in adherence. Therefore IgG Fab fragments were prepared to study the functional role of PhtD and PhtE-specific Fabs in blocking adherence. The addition of 1 μg of IgG Fab from adult sera led to a 34% reduction (p= 0.002) and from children a 20% (p= 0.023) reduction in D562 epithelial cells with adherent pneumococci. In purified IgG from adult sera, the depletion of PhtD and PhtE specific Fab from total IgG Fab resulted in a significant increase in the number of D562 epithelial cells with adherent pneumococci (p=0.005 for PhtD and p=0.024 for PhtE). We conclude that antibody directed to PhtD and PhtE are adhesins of pneumococci, if raised by vaccination, may function to prevent pneumococcal adherence to human airway epithelial cells.",,"['Khan, M. Nadeem', 'Pichichero, Michael E.']",,,,
,PMC,Enhanced outgrowth of EBV-transformed chronic lymphocytic leukemia B cells mediated by coculture with macrophage feeder cells,http://dx.doi.org/10.1182/blood-2011-08-371203,PMC3286354,,,"B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the clonal expansion of CD5-expressing B lymphocytes that produce mAbs often reactive with microbial or autoantigens. Long-term culture of B-CLL clones would permit the collection and characterization of B-CLL mAbs to study antigen specificity and of B-CLL DNA to investigate molecular mechanisms promoting the disease. However, the derivation of long-term cell lines (eg, by EBV), has not been efficient. We have improved the efficiency of EBV B-CLL transformation of CpG oligonucleotide-stimulated cells by incubating patient peripheral blood mononuclear cells in the presence of an irradiated mouse macrophage cell line, J774A.1. Using this approach, peripheral blood mononuclear cells isolated from 13 of 21 B-CLL patients were transformed as documented by IGHV-D-J sequencing. Four clones grew and retained CD5 expression in culture for 2 to 4 months. However, despite documentation of EBV infection by expression of EBNA2 and LMP1, B-CLL cells died after removal of macrophage feeder cells. Nevertheless, using electrofusion technology, we generated 6 stable hetero-hybridoma cell lines from EBV-transformed B-CLL cells, and these hetero-hybridomas produced immunoglobulin. Thus, we have established enhanced methods of B-CLL culture that will enable broader interrogation of B-CLL cells at the genetic and protein levels.",,"['Hwang, Kwan-Ki', 'Chen, Xi', 'Kozink, Daniel M.', 'Gustilo, Marietta', 'Marshall, Dawn J.', 'Whitesides, John F.', 'Liao, Hua-Xin', 'Catera, Rosa', 'Chu, Charles C.', 'Yan, Xiao-Jie', 'Luftig, Micah A.', 'Haynes, Barton F.', 'Chiorazzi, Nicholas']",,,,
,PMC,Influenza A Virus Induces Interleukin-27 through Cyclooxygenase-2 and Protein Kinase A Signaling,http://dx.doi.org/10.1074/jbc.M111.308064,PMC3320938,,,"We previously reported that IL-27, which belongs to the IL-12 family of cytokines, is elevated in the serum of patients infected with influenza A virus (IAV). Here, we show that the expression of IL-27 was significantly up-regulated in A549 human lung epithelial cells and human peripheral blood mononuclear cells infected with IAV. Additionally, IAV triggered IL-27 expression through protein kinase A and cAMP-response element-binding protein signaling, which was mediated by cyclooxygenase-2-derived prostaglandin E(2). IL-27 inhibited IAV replication by STAT1/2/3 phosphorylation and activated antiviral factor protein kinase R phosphorylation. Clinical analysis showed that IL-27 levels were significantly elevated in a cohort of patients infected with IAV compared with healthy individuals and that circulating IL-27 levels were tightly and positively correlated with prostaglandin E(2) levels. These results indicate that IL-27 expression is one host immune factor produced in response to IAV infection and that elevated IL-27 levels inhibit viral replication.",,"['Liu, Li', 'Cao, Zhongying', 'Chen, Jing', 'Li, Rui', 'Cao, Yanhua', 'Zhu, Chengliang', 'Wu, Kailang', 'Wu, Jianguo', 'Liu, Fang', 'Zhu, Ying']",,,,
,PMC,Hypoalbuminemia and Early Mortality After Lung Transplantation: A Cohort Study,http://dx.doi.org/10.1111/j.1600-6143.2011.03965.x,PMC3628840,,,"Hypoalbuminemia predicts disability and mortality in patients with various illnesses and in the elderly. The association between serum albumin concentration at the time of listing for lung transplantation and the rate of death after lung transplantation is unknown. We examined 6808 adults who underwent lung transplantation in the United States between 2000 and 2008. We used Cox proportional hazard models and generalized additive models to examine multivariable-adjusted associations between serum albumin and the rate of death after transplantation. The median follow-up time was 2.7 years. Those with severe (0.5–2.9 g/dL) and mild hypoalbuminemia (3.0–3.6 g/dL) had posttransplant adjusted mortality rate ratios of 1.35 (95% CI: 1.12–1.62) and 1.15 (95% CI: 1.04–1.27), respectively. For each 0.5 g/dL decrease in serum albumin concentration the 1-year and overall mortality rate ratios were 1.48 (95% CI: 1.21–1.81) and 1.26 (95% CI: 1.11–1.43), respectively. The association between hypoalbuminemia and posttransplant mortality was strongest in recipients with cystic fibrosis and interstitial lung disease. Hypoalbuminemia is an independent risk factor for death after lung transplantation.",,"['Baldwin, M. R.', 'Arcasoy, S. M.', 'Shah, A.', 'Schulze, P. C.', 'Sze, J.', 'Sonett, J. R.', 'Lederer, D. J.']",,,,
,PMC,Hapivirins and Diprovirins: Novel θ-Defensin Analogs With Potent Activity Against Influenza A Virus(),http://dx.doi.org/10.4049/jimmunol.1101335,PMC3294087,,,"θ-defensins are cyclic octadecapeptides found in non-human primates whose broad antiviral-spectrum includes HIV-1, HSV-1, SARS, and influenza A virus (IAV). We previously reported that synthetic θ-defensins called retrocyclins can neutralize and aggregate various strains of IAV and increase IAV uptake by neutrophils. This report describes two families of peptides, hapivirins (HpVs) and diprovirins (DpVs), whose design was inspired by retrocyclins. The goal was to develop smaller partially cyclic peptides that retain the antiviral activity of retrocyclins, while being easier to synthesize. The novel peptides also allowed for systemic substitution of key residues to evaluate the role of charge or hydrophobicity on antiviral activity. Seventy-two HpV or DpV peptides are described in this report, including several whose anti-IAV activity equals or exceeds that of normal α– or θ-defensins. Some of these also had strong antibacterial and antifungal activity. These new peptides were active against H3N2 and H1N1 strains of IAV. Structural features imparting strong antiviral activity were identified through iterative cycles of synthesis and testing. Our findings show the importance of hydrophobic residues for antiviral activity and show that pegylation, which often increases a peptide’s serum half-life in vivo, can increase the antiviral activity of DpVs. The new peptides acted at an early phase of viral infection and when combined with pulmonary surfactant protein D, their antiviral effects were additive. The peptides strongly increased neutrophil and macrophage uptake of IAV, while inhibiting monocyte cytokine generation. Development of modified θ– defensin analogues provides an approach for creating novel antiviral agents for IAV infections.",,"['Doss, Mona', 'Ruchala, Piotr', 'Tecle, Tesfaldet', 'Gantz, Donald', 'Verma, Anamika', 'Hartshorn, Alex', 'Crouch, Erika C.', 'Luong, Hai', 'Micewicz, Ewa D.', 'Lehrer, Robert I.', 'Hartshorn, Kevan L.']",,,,
,PMC,Discrimination of influenza A subtype by antibodies recognizing host‐specific amino acids in the viral nucleoprotein,http://dx.doi.org/10.1111/j.1750-2659.2012.00335.x,PMC6505565,,,"Please cite this paper as: Miyoshi‐Akiyama et al. (2012) Discrimination of influenza A subtype by antibodies recognizing host‐specific amino acids in the viral nucleoprotein. Influenza and Other Respiratory Viruses 6(6), 434–441. Background  Nucleoprotein (NP) of influenza viruses is utilized to differentiate between the A, B, and C viral serotypes. The availability of influenza genome sequence data has allowed us to identify specific amino acids at particular positions in viral proteins, including NP, known as “signature residues,” which can be used to discriminate human influenza A viruses from H5N1 highly pathogenic avian influenza in human cases (HPAI) and pandemic H1N1(2009) (H1N1/2009) viruses. Methods  Screening and epitope mapping of monoclonal antibodies (mAb) against NP of influenza A, which reacted differently with NP from human influenza A virus from HPAI and H1N1/2009 A virus. To identify the epitope(s) responsible for the discrimination of viral NP by mAbs, we prepared mutant NP proteins in the 293 cell expression system because some of the mAbs reacted with non‐linear epitopes. Results and Conclusions  In the present study, we identified 3 mAbs. The results of epitope mapping showed that the epitopes were located at the signature residues. These results indicated that signature residues of NP could discriminate influenza A viruses from different origin.",,"['Miyoshi‐Akiyama, Tohru', 'Yamashiro, Tetsu', 'Mai, Le Quynh', 'Narahara, Kenji', 'Miyamoto, Akitomo', 'Shinagawa, Shingo', 'Mori, Sunao', 'Kitajima, Hirotake', 'Kirikae, Teruo']",,,,
,PMC,Delivery strategies for novel vaccine formulations,http://dx.doi.org/10.5501/wjv.v1.i1.4,PMC3782264,,,"A major challenge in vaccine design is to identify antigen presentation and delivery systems capable of rapidly stimulating both the humoral and cellular components of the immune system to elicit a strong and sustained immunity against different viral isolates. Approaches to achieve this end involve live attenuated and inactivated virions, viral vectors, DNA, and protein subunits. This review reports the state of current antigen delivery, and focuses on two innovative systems recently established at our labs. These systems are the filamentous bacteriophage fd and an icosahedral scaffold formed by the acyltransferase component (E2 protein) of the pyruvate dehydrogenase complex of Bacillus stearothermophilus.",,"['Trovato, Maria', 'Krebs, Shelly J', 'Haigwood, Nancy L', 'De Berardinis, Piergiuseppe']",,,,
,PMC,Emerging and re-emerging viruses: A global challenge illustrated by Chikungunya virus outbreaks,http://dx.doi.org/10.5501/wjv.v1.i1.11,PMC3782263,,,"In recent decades, the issue of emerging and re-emerging infectious diseases, especially those related to viruses, has become an increasingly important area of concern in public health. It is of significance to anticipate future epidemics by accumulating knowledge through appropriate research and by monitoring their emergence using indicators from different sources. The objective is to alert and respond effectively in order to reduce the adverse impact on the general populations. Most of the emerging pathogens in humans originate from known zoonosis. These pathogens have been engaged in long-standing and highly successful interactions with their hosts since their origins are exquisitely adapted to host parasitism. They developed strategies aimed at: (1) maximizing invasion rate; (2) selecting host traits that can reduce their impact on host life span and fertility; (3) ensuring timely replication and survival both within host and between hosts; and (4) facilitating reliable transmission to progeny. In this context, Arboviruses (or ARthropod-BOrne viruses), will represent with certainty a threat for the coming century. The unprecedented epidemic of Chikungunya virus which occurred between 2005 and 2006 in the French Reunion Island in the Indian Ocean, followed by several outbreaks in other parts of the world, such as India and Southern Europe, has attracted the attention of medical and state authorities about the risks linked to this re-emerging mosquito-borne virus. This is an excellent model to illustrate the issues we are facing today and to improve how to respond tomorrow.",,"Devaux, Christian A",,,,
,PMC,Face up to challenge of virology world,http://dx.doi.org/10.5501/wjv.v1.i1.1,PMC3782262,,,"Welcome to the World Journal of Virology (WJV), a new member of the World Journal Series. The World Journal Series was first launched as a peer-reviewed scientific journal covering aspects of research, diagnostics and clinical practice in biomedicine in 1995. WJV is an online and open-access peer-reviewed periodical focusing on virology. WJV covers a variety of topics in different areas of virology, including advances in basic research, updates in nomenclature, the development of novel diagnostic assays, the epidemiology of viral disorders and, new developments in the clinical management of viral diseases, including new vaccines and antiviral therapeutics. The purpose in launching the WJV is to promote knowledge exchange related to the classic human viruses as well as newly emerging viruses and their associated clinical disorders. Continually updating knowledge in a timely manner in this field where information related to the unceasing evolution of viruses is becoming available at a rapid pace is challenging. Thanks to the World-Wide-Web we are able to provide a podium for all authors and readers of WJV to address this challenge. I would like to acknowledge the Baishideng publisher, the members of the editorial board, and all contributing authors involved in this inaugural issue of the WJV. I sincerely hope all readers, i.e. future contributing authors, will like WJV and we look forward to your input in assisting WJV to grow and mature.",,"Pang, Xiaoli Lilly",,,,
,PMC,The role of antigen-presenting cells in filoviral hemorrhagic fever: gaps in current knowledge,http://dx.doi.org/10.1016/j.antiviral.2012.01.011,PMC3299938,,,"The filoviruses, ebolavirus (EBOV) and marburgvirus (MARV), are highly lethal zoonotic agents of concern as emerging pathogens and potential bioweapons. Antigen-presenting cells (APCs), particularly macrophages and dendritic cells, are targets of filovirus infection in vivo. Infection of these cell types has been proposed to contribute to the inflammation, activation of coagulation cascades and ineffective immune responses characteristic of filovirus hemorrhagic fever. However, many aspects of filovirus-APC interactions remain to be clarified. Among the unanswered questions: What determines the ability of filoviruses to replicate in different APC subsets? What are the cellular signaling pathways that sense infection and lead to production of copious quantities of cytokines, chemokines and tissue factor? What are the mechanisms by which innate antiviral responses are disabled by these viruses, and how may these mechanisms contribute to inadequate adaptive immunity? A better understanding of these issues will clarify the pathogenesis of filoviral hemorrhagic fever and provide new avenues for development of therapeutics.",,"['Martinez, Osvaldo', 'Leung, Lawrence W.', 'Basler, Christopher F.']",,,,
,PMC,Plasmacytoid dendritic cells control T-cell response to chronic viral infection,http://dx.doi.org/10.1073/pnas.1117359109,PMC3286988,,,"Infections with persistent viruses are a frequent cause of immunosuppression, autoimmune sequelae, and/or neoplastic disease. Plasmacytoid dendritic cells (pDCs) are innate immune cells that produce type I interferon (IFN-I) and other cytokines in response to virus-derived nucleic acids. Persistent viruses often cause depletion or functional impairment of pDCs, but the role of pDCs in the control of these viruses remains unclear. We used conditional targeting of pDC-specific transcription factor E2-2 to generate mice that constitutively lack pDCs in peripheral lymphoid organs and tissues. The profound impact of pDC deficiency on innate antiviral responses was revealed by the failure to control acute infection with the cytopathic mouse hepatitis virus. Furthermore, pDC-deficient animals failed to clear lymphocytic choriomeningitis virus (LCMV) from hematopoietic organs during persistent LCMV infection. This failure was associated with reduced numbers and functionality of LCMV-specific CD4(+) helper T cells and impaired antiviral CD8(+) T-cell responses. Adoptive transfer of LCMV-specific T cells revealed that both CD4(+) and CD8(+) T cells required IFN-I for expansion, but only CD4(+) T cells required the presence of pDCs. In contrast, mice with pDC-specific loss of MHC class II expression supported normal CD4(+) T-cell response to LCMV. These data suggest that pDCs facilitate CD4(+) helper T-cell responses to persistent viruses independently of direct antigen presentation. Thus pDCs provide an essential link between innate and adaptive immunity to chronic viral infection, likely through the secretion of IFN-I and other cytokines.",,"['Cervantes-Barragan, Luisa', 'Lewis, Kanako L.', 'Firner, Sonja', 'Thiel, Volker', 'Hugues, Stephanie', 'Reith, Walter', 'Ludewig, Burkhard', 'Reizis, Boris']",,,,
,PMC,Protein phosphatase 1 subunit Ppp1r15a/GADD34 regulates cytokine production in polyinosinic:polycytidylic acid-stimulated dendritic cells,http://dx.doi.org/10.1073/pnas.1104491109,PMC3286954,,,"In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation that exhibits specific mechanisms to control the immune response. Here we show that in response to polyriboinosinic:polyribocytidylic acid (pI:C), DCs mount a specific integrated stress response during which the transcription factor ATF4 and the growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), a phosphatase 1 (PP1) cofactor, are expressed. In agreement with increased GADD34 levels, an extensive dephosphorylation of the translation initiation factor eIF2α was observed during DC activation. Unexpectedly, although DCs display an unusual resistance to protein synthesis inhibition induced in response to cytosolic dsRNA, GADD34 expression did not have a major impact on protein synthesis. GADD34, however, was shown to be required for normal cytokine production both in vitro and in vivo. These observations have important implications in linking further pathogen detection with the integrated stress response pathways.",,"['Clavarino, Giovanna', 'Cláudio, Nuno', 'Dalet, Alexandre', 'Terawaki, Seigo', 'Couderc, Thérèse', 'Chasson, Lionel', 'Ceppi, Maurizio', 'Schmidt, Enrico K.', 'Wenger, Till', 'Lecuit, Marc', 'Gatti, Evelina', 'Pierre, Philippe']",,,,
,PMC,Enteritis associated with Clostridium perfringens type A in 9-month-old calves,,PMC3258831,,,"Four 9-month-old Simmental male calves were presented with a history of sudden death. The necropsy and microscopic findings allowed a diagnosis of enteritis and severe intraluminal hemorrhage with blood clots in the jejunum, suggestive of jejunal hemorrhage syndrome.",,"['Savic, Bozidar', 'Prodanovic, Radisa', 'Ivetic, Vojin', 'Radanovic, Oliver', 'Bojkovski, Jovan']",,,,
,PMC,Transcriptional and Posttranscriptional Regulation of HIV-1 Gene Expression,http://dx.doi.org/10.1101/cshperspect.a006916,PMC3281586,,,"Control of HIV-1 gene expression depends on two viral regulatory proteins, Tat and Rev. Tat stimulates transcription elongation by directing the cellular transcriptional elongation factor P-TEFb to nascent RNA polymerases. Rev is required for the transport from the nucleus to the cytoplasm of the unspliced and incompletely spliced mRNAs that encode the structural proteins of the virus. Molecular studies of both proteins have revealed how they interact with the cellular machinery to control transcription from the viral LTR and regulate the levels of spliced and unspliced mRNAs. The regulatory feedback mechanisms driven by HIV-1 Tat and Rev ensure that HIV-1 transcription proceeds through distinct phases. In cells that are not fully activated, limiting levels of Tat and Rev act as potent blocks to premature virus production.",,"['Karn, Jonathan', 'Stoltzfus, C. Martin']",,,,
,PMC,Technologies for enhanced efficacy of DNA vaccines,http://dx.doi.org/10.1586/erv.11.188,PMC3293989,,,"Despite many years of research, human DNA vaccines have yet to fulfill their early promise. Over the past 15 years, multiple generations of DNA vaccines have been developed and tested in preclinical models for prophylactic and therapeutic applications in the areas of infectious disease and cancer, but have failed in the clinic. Thus, while DNA vaccines have achieved successful licensure for veterinary applications, their poor immunogenicity in humans when compared with traditional protein-based vaccines has hindered their progress. Many strategies have been attempted to improve DNA vaccine potency including use of more efficient promoters and codon optimization, addition of traditional or genetic adjuvants, electroporation, intradermal delivery and various prime–boost strategies. This review summarizes these advances in DNA vaccine technologies and attempts to answer the question of when DNA vaccines might eventually be licensed for human use.",,"['Saade, Fadi', 'Petrovsky, Nikolai']",,,,
,PMC,Neuro-invasion by a ‘Trojan Horse’ strategy and vasculopathy during intrauterine flavivirus infection,http://dx.doi.org/10.1111/j.1365-2613.2011.00795.x,PMC3311019,,,"The central nervous system (CNS) is a major target of several important human and animal viral pathogens causing congenital infections. However, despite the importance of neuropathological outcomes, for humans in particular, the pathogenesis, including mode of neuro-invasion, remains unresolved for most congenital virus infections. Using a natural model of congenital infection with an RNA virus, bovine viral diarrhoea virus in pregnant cattle, we sought to delineate the timing and mode of virus neuro-invasion of and spread within the brain of foetuses following experimental respiratory tract infection of the dams at day 75 of pregnancy, a time of maximal risk of tissue pathology without foetal death. Virus antigen was first detected in the foetal brains 14 days postinfection of dams and was initially restricted to amoeboid microglial cells in the periventricular germinal layer. The appearance of these cells was preceded by or concurrent with vasculopathy in the same region. While the affected microvessels were negative for virus antigen, they expressed high levels of the type I interferon-stimulated protein ISG15 and eventually disappeared in parallel with the appearance of microcavitary lesions. Subsequently, the virus spread to neurons and other glial cells. Our findings suggest that the virus enters the CNS via infected microglial precursors, the amoeboid microglial cells, in a ‘Trojan horse’ mode of invasion and that the microcavitary lesions are associated with loss of periventricular microvasculature, perhaps as a consequence of high, unrestricted induction of interferon-regulated proteins.",,"['Bielefeldt-Ohmann, Helle', 'Smirnova, Natalia P', 'Tolnay, Airn-Elizabeth', 'Webb, Brett T', 'Antoniazzi, Alfredo Q', 'van Campen, Hana', 'Hansen, Thomas R']",,,,
,PMC,Microvesicles at the crossroads between infection and cardiovascular diseases,http://dx.doi.org/10.1097/FJC.0b013e31820c6254,PMC3090703,,,"Observational and experimental studies continue to support the association of infection and infection-stimulated inflammation with development of cardiovascular disease (CVD) including atherosclerosis and thrombosis. Microvesicles (MV) are heterogeneous populations of sealed membrane-derived vesicles shed into circulation by activated mammalian cells and/or pathogenic microbes that may represent an interface between bacterial/microbial infection and increased risk of CVD. This review evaluates how MV act to modulate and intersect immunological and inflammatory responses to infection with particular attention to progression of CVD. While infection-related stimuli provoke release of MV from blood and vascular cells, MV express phosphatidylserine (PS) and other procoagulant factors on their surface which initiate and amplify blood coagulation. In addition, MV mediate cell-cell adhesion which may stimulate production of pro-inflammatory cytokines in vascular cells, which in turn aggravate progression of CVD and propagate atherothrombosis. MV transfer membrane receptors, RNA and proteins among cells, and present auto-antigens from their cells of origin to proximal or remote target cells. Because MV harbor cell surface proteins and contain cytoplasmic components of the parent cell, they mediate biological messages and play a pivotal role in the crossroad between infection-stimulated inflammation and cardiovascular diseases.",,"['Xiong, Jing', 'Miller, Virginia M.', 'Li, Yunman', 'Jayachandran, Muthuvel']",,,,
,PMC,Comparison of the Idaho Technology FilmArray System to Real-Time PCR for Detection of Respiratory Pathogens in Children,http://dx.doi.org/10.1128/JCM.05996-11,PMC3264185,,,"The FilmArray Respiratory Panel (RP) multiplexed nucleic acid amplification test (Idaho Technology, Inc., Salt Lake City, UT) was compared to laboratory-developed real-time PCR assays for the detection of various respiratory viruses and certain bacterial pathogens. A total of 215 frozen archived pediatric respiratory specimens previously characterized as either negative or positive for one or more pathogens by real-time PCR were examined using the FilmArray RP system. Overall agreement between the FilmArray RP and corresponding real-time PCR assays for shared analytes was 98.6% (kappa = 0.92 [95% confidence interval (CI), 0.89 to 0.94]). The combined positive percent agreement was 89.4% (95% CI, 85.4 to 92.6); the negative percent agreement was 99.6% (95% CI, 99.2 to 99.8). The mean real-time PCR threshold cycle (C(T)) value for specimens with discordant results was 36.46 ± 4.54. Detection of coinfections and correct identification of influenza A virus subtypes were comparable to those of real-time PCR when using the FilmArray RP. The greatest comparative difference in sensitivity was observed for adenovirus; only 11 of 24 (45.8%; 95% CI, 27.9 to 64.9) clinical specimens positive for adenovirus by real-time PCR were also positive by the FilmArray RP. In addition, upon testing 20 characterized adenovirus serotypes prepared at high and low viral loads, the FilmArray RP did not detect serotypes 6 and 41 at either level and failed to detect serotypes 2, 20, 35, and 37 when viral loads were low. The FilmArray RP system is rapid and extremely user-friendly, with results available in just over 1 h with almost no labor involved. Its low throughput is a significant drawback for laboratories receiving large numbers of specimens, as only a single sample can be processed at a time with one instrument.",,"['Pierce, Virginia M.', 'Elkan, Michael', 'Leet, Marilyn', 'McGowan, Karin L.', 'Hodinka, Richard L.']",,,,
,PMC,"Picornavirus, the Most Common Respiratory Virus Causing Infection among Patients of All Ages Hospitalized with Acute Respiratory Illness",http://dx.doi.org/10.1128/JCM.05999-11,PMC3264172,,,"We evaluated the prevalence of respiratory virus infection (RVI) in 403 illnesses of 364 persons hospitalized over a 2-year period with acute respiratory conditions using virus-specific reverse transcription-PCR (RT-PCR) assays in addition to cell culture and serology. RVIs were identified in >75% of children under 5 years of age and 25 to 37% of adults. The molecular assays doubled the number of infections identified; picornaviruses were the most frequent in patients of all ages, followed by respiratory syncytial virus and influenza viruses.",,"['Atmar, Robert L.', 'Piedra, Pedro A.', 'Patel, Shital M.', 'Greenberg, Stephen B.', 'Couch, Robert B.', 'Glezen, W. Paul']",,,,
,PMC,Examining the cross-reactivity and neutralization mechanisms of a panel of mAbs against adeno-associated virus serotypes 1 and 5,http://dx.doi.org/10.1099/vir.0.035113-0,PMC3352341,,,"Neutralizing antibodies play a central role in the prevention and clearance of viral infections, but can be detrimental to the use of viral capsids for gene delivery. Antibodies present a major hurdle for ongoing clinical trials using adeno-associated viruses (AAVs); however, relatively little is known about the antigenic epitopes of most AAV serotypes or the mechanism(s) of antibody-mediated neutralization. We developed panels of AAV mAbs by repeatedly immunizing mice with AAV serotype 1 (AAV1) capsids, or by sequentially immunizing with AAV1 followed by AAV5 capsids, in order to examine the efficiency and mechanisms of antibody-mediated neutralization. The antibodies were not cross-reactive between heterologous AAV serotypes except for a low level of recognition of AAV1 capsids by the AAV5 antibodies, probably due to the initial immunization with AAV1. The neutralization efficiency of different IgGs varied and Fab fragments derived from these antibodies were generally poorly neutralizing. The antibodies appeared to display various alternative mechanisms of neutralization, which included inhibition of receptor-binding and interference with a post-attachment step.",,"['Harbison, Carole E.', 'Weichert, Wendy S.', 'Gurda, Brittney L.', 'Chiorini, John A.', 'Agbandje-McKenna, Mavis', 'Parrish, Colin R.']",,,,
,PMC,Involvement of the Rho kinases in mediating sepsis,http://dx.doi.org/10.3978/j.issn.2072-1439.2011.09.06,PMC3256547,,,,,"Tai, T.C.",,,,
,PMC,Viral Interferon Regulatory Factors Decrease the Induction of Type I and Type II Interferon during Rhesus Macaque Rhadinovirus Infection,http://dx.doi.org/10.1128/JVI.05047-11,PMC3302421,,,"Kaposi's sarcoma-associated herpesvirus and rhesus macaque rhadinovirus (RRV), two closely related gammaherpesviruses, are unique in their expression of viral homologs of cellular interferon regulatory factors (IRFs), termed viral IRFs (vIRFs). To assess the role of vIRFs during de novo infection, we have utilized the bacterial artificial chromosome clone of wild-type RRV(17577) (WT(BAC) RRV) to generate a recombinant virus with all 8 of the vIRFs deleted (vIRF-ko RRV). The infection of primary rhesus fibroblasts and peripheral blood mononuclear cells (PBMCs) with vIRF-ko RRV resulted in earlier and increased induction of type I interferon (IFN) (IFN-α/β) and type II IFN (IFN-γ). Additionally, plasmacytoid dendritic cells maintained higher levels of IFN-α production in PBMC cultures infected with vIRF-ko RRV than in cultures infected with WT(BAC) RRV. Moreover, the nuclear accumulation of phosphorylated IRF-3, which is necessary for the induction of type I IFN, was also inhibited following WT(BAC) RRV infection. These findings demonstrate that during de novo RRV infection, vIRFs are inhibiting the induction of IFN at the transcriptional level, and one potential mechanism for this is the disruption of the activation and localization of IRF-3.",,"['Robinson, Bridget A.', 'Estep, Ryan D.', 'Messaoudi, Ilhem', 'Rogers, Kelsey S.', 'Wong, Scott W.']",,,,
,PMC,Identification of Cell Surface Molecules Involved in Dystroglycan-Independent Lassa Virus Cell Entry,http://dx.doi.org/10.1128/JVI.06451-11,PMC3302412,,,"Although O-mannosylated dystroglycan is a receptor for Lassa virus, a causative agent of Lassa fever, recent findings suggest the existence of an alternative receptor(s). Here we identified four molecules as receptors for Lassa virus: Axl and Tyro3, from the TAM family, and dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and liver and lymph node sinusoidal endothelial calcium-dependent lectin (LSECtin), from the C-type lectin family. These molecules enhanced the binding of Lassa virus to cells and mediated infection independently of dystroglycan. Axl- or Tyro3-mediated infection required intracellular signaling via the tyrosine kinase activity of Axl or Tyro3, whereas DC-SIGN- or LSECtin-mediated infection and binding were dependent on a specific carbohydrate and on ions. The identification of these four molecules as Lassa virus receptors advances our understanding of Lassa virus cell entry.",,"['Shimojima, Masayuki', 'Ströher, Ute', 'Ebihara, Hideki', 'Feldmann, Heinz', 'Kawaoka, Yoshihiro']",,,,
,PMC,The Andes Hantavirus NSs Protein Is Expressed from the Viral Small mRNA by a Leaky Scanning Mechanism,http://dx.doi.org/10.1128/JVI.06223-11,PMC3302399,,,"The small mRNA (SmRNA) of all Bunyaviridae encodes the nucleocapsid (N) protein. In 4 out of 5 genera in the Bunyaviridae, the smRNA encodes an additional nonstructural protein denominated NSs. In this study, we show that Andes hantavirus (ANDV) SmRNA encodes an NSs protein. Data show that the NSs protein is expressed in the context of an ANDV infection. Additionally, our results suggest that translation initiation from the NSs initiation codon is mediated by ribosomal subunits that have bypassed the upstream N protein initiation codon through a leaky scanning mechanism.",,"['Vera-Otarola, Jorge', 'Solis, Loretto', 'Soto-Rifo, Ricardo', 'Ricci, Emiliano P.', 'Pino, Karla', 'Tischler, Nicole D.', 'Ohlmann, Théophile', 'Darlix, Jean-Luc', 'López-Lastra, Marcelo']",,,,
,PMC,Development of a Novel Nonhuman Primate Model for Rift Valley Fever,http://dx.doi.org/10.1128/JVI.06190-11,PMC3302397,,,"Rift Valley fever (RVF) virus (RVFV) can cause severe human disease characterized by either acute-onset hepatitis, delayed-onset encephalitis, retinitis and blindness, or a hemorrhagic syndrome. The existing nonhuman primate (NHP) model for RVF utilizes an intravenous (i.v.) exposure route in rhesus macaques (Macaca mulatta). Severe disease in these animals is infrequent, and large cohorts are needed to observe significant morbidity and mortality. To overcome these drawbacks, we evaluated the infectivity and pathogenicity of RVFV in the common marmoset (Callithrix jacchus) by i.v., subcutaneous (s.c.), and intranasal exposure routes to more closely mimic natural exposure. Marmosets were more susceptible to RVFV than rhesus macaques and experienced higher rates of morbidity, mortality, and viremia and marked aberrations in hematological and chemistry values. An overwhelming infection of hepatocytes was a major consequence of infection of marmosets by the i.v. and s.c. exposure routes. Additionally, these animals displayed signs of hemorrhagic manifestations and neurological impairment. Based on our results, the common marmoset model more closely resembles severe human RVF disease and is therefore an ideal model for the evaluation of potential vaccines and therapeutics.",,"['Smith, Darci R.', 'Bird, Brian H.', 'Lewis, Bridget', 'Johnston, Sara C.', 'McCarthy, Sarah', 'Keeney, Ashley', 'Botto, Miriam', 'Donnelly, Ginger', 'Shamblin, Joshua', 'Albariño, César G.', 'Nichol, Stuart T.', 'Hensley, Lisa E.']",,,,
,PMC,Productive Replication and Evolution of HIV-1 in Ferret Cells,http://dx.doi.org/10.1128/JVI.06035-11,PMC3302389,,,"A rodent or other small animal model for HIV-1 has not been forthcoming, with the principal obstacles being species-specific restriction mechanisms and deficits in HIV-1 dependency factors. Some Carnivorans may harbor comparatively fewer impediments. For example, in contrast to mice, the domestic cat genome encodes essential nonreceptor HIV-1 dependency factors. All Feliformia species and at least one Caniformia species also lack a major lentiviral restriction mechanism (TRIM5α/TRIMCyp proteins). Here we investigated cells from two species in another carnivore family, the Mustelidae, for permissiveness to the HIV-1 life cycle. Mustela putorius furo (domesticated ferret) primary cells and cell lines did not restrict HIV-1, feline immunodeficiency virus (FIV), equine infectious anemia virus (EIAV), or N-tropic murine leukemia virus (MLV) postentry and supported late HIV-1 life cycle steps comparably to human cells. The ferret TRIM5α gene exon 8, which encodes the B30.2 domain, was found to be pseudogenized. Strikingly, ferret (but not mink) cells engineered to express human HIV-1 entry receptors supported productive spreading replication, amplification, and serial passage of wild-type HIV-1. Nevertheless, produced virions had relatively reduced infectivity and the virus accrued G→A hypermutations, consistent with APOBEC3 protein pressure. Ferret cell-passaged HIV-1 also evolved amino acid changes in the capsid cyclophilin A binding loop. We conclude that the genome of this carnivore can provide essential nonreceptor HIV-1 dependency factors and that ferret APOBEC3 proteins with activity against HIV-1 are likely. Even so, unlike in cat cells, HIV-1 can replicate in ferret cells without vif substitution. The virus evolves in this novel nonprimate cell adaptive landscape. We suggest that further characterization of HIV-1 adaptation in ferret cells and delineation of Mustelidae restriction factor repertoires are warranted, with a view to the potential for an HIV-1 animal model.",,"['Fadel, Hind J.', 'Saenz, Dyana T.', 'Guevara, Rebekah', 'von Messling, Veronika', 'Peretz, Mary', 'Poeschla, Eric M.']",,,,
,PMC,The Vaccinia Virus O1 Protein Is Required for Sustained Activation of Extracellular Signal-Regulated Kinase 1/2 and Promotes Viral Virulence,http://dx.doi.org/10.1128/JVI.06166-11,PMC3302380,,,"Sustained activation of the Raf/MEK/extracellular signal-regulated kinase (ERK) pathway in infected cells has been shown to be crucial for full replication efficiency of orthopoxviruses in cell culture. In infected cells, this pathway is mainly activated by the vaccinia virus growth factor (VGF), an epidermal growth factor (EGF)-like protein. We show here that chorioallantois vaccinia virus Ankara (CVA), but not modified vaccinia virus Ankara (MVA), induced sustained activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in infected human 293 cells, although both viruses direct secretion of functional VGF. A CVA mutant lacking the O1L gene (CVA-ΔO1L) demonstrated that the O1 protein was required for sustained upregulation of the ERK1/2 pathway in 293 cells as well as in other mammalian cell lines. The highly conserved orthopoxvirus O1L gene encodes a predicted 78-kDa protein with a hitherto-unknown function. CVA-ΔO1L showed reduced plaque size and an attenuated cytopathic effect (CPE) in infected cell cultures and reduced virulence and spread from lungs to ovaries in intranasally infected BALB/c mice. Reinsertion of an intact O1L gene into MVA, which in its original form harbors a fragmented O1L open reading frame (ORF), restored ERK1/2 activation in 293 cells but did not increase replication and spread of MVA in human or other mammalian cell lines. Thus, the O1 protein was crucial for sustained ERK1/2 activation in CVA- and MVA-infected human cells, complementing the autocrine function of VGF, and enhanced virulence in vivo.",,"['Schweneker, Marc', 'Lukassen, Susanne', 'Späth, Michaela', 'Wolferstätter, Michael', 'Babel, Eveline', 'Brinkmann, Kay', 'Wielert, Ursula', 'Chaplin, Paul', 'Suter, Mark', 'Hausmann, Jürgen']",,,,
,PMC,Metagenomic Analysis of the Viral Flora of Pine Marten and European Badger Feces,http://dx.doi.org/10.1128/JVI.06373-11,PMC3302375,,,"A thorough understanding of the diversity of viruses in wildlife provides epidemiological baseline information about potential pathogens. Metagenomic analysis of the enteric viral flora revealed a new anellovirus and bocavirus species in pine martens and a new circovirus-like virus and geminivirus-related DNA virus in European badgers. In addition, sequences with homology to viruses from the families Paramyxo- and Picornaviridae were detected.",,"['van den Brand, Judith M. A.', 'van Leeuwen, Marije', 'Schapendonk, Claudia M.', 'Simon, James H.', 'Haagmans, Bart L.', 'Osterhaus, Albert D. M. E.', 'Smits, Saskia L.']",,,,
,PMC,Respiratory Syncytial Virus Glycoprotein G Interacts with DC-SIGN and L-SIGN To Activate ERK1 and ERK2,http://dx.doi.org/10.1128/JVI.06096-11,PMC3264376,,,"Respiratory syncytial virus (RSV) interaction with epithelial and dendritic cells (DCs) is known to require divalent cations, suggesting involvement of C-type lectins. RSV infection and maturation of primary human DCs are reduced in a dose-dependent manner by EDTA. Therefore, we asked whether RSV infection involves DC-SIGN (CD209) or its isoform L-SIGN (CD299) (DC-SIGN/R). Using surface plasmon resonance analysis, we demonstrated that the attachment G glycoprotein of RSV binds both DC- and L-SIGN. However, neutralization of DC- and L-SIGN on primary human DCs did not inhibit RSV infection, demonstrating that interactions between RSV G and DC- or L-SIGN are not required for productive infection. Thus, neither DC- nor L-SIGN represents a functional receptor for RSV. However, inhibition of these interactions increased DC activation, as evidenced by significantly higher levels of alpha interferon (IFN-α), MIP-1α, and MIP-1β in plasmacytoid DCs (pDCs) exposed to RSV after neutralization of DC-and L-SIGN. To understand the molecular interactions involved, intracellular signaling events triggered by purified RSV G glycoprotein were examined in DC- and L-SIGN-transfected 3T3 cells. RSV G interaction with DC- or L-SIGN was shown to stimulate ERK1 and ERK2 phosphorylation, with statistically significant increases relative to mock-infected cells. Neutralization of DC- and L-SIGN reduced ERK1/2 phosphorylation. With increased DC activation following DC- and L-SIGN neutralization and RSV exposure, these data demonstrate that the signaling events mediated by RSV G interactions with DC/L-SIGN are immunomodulatory and diminish DC activation, which may limit induction of RSV-specific immunity.",,"['Johnson, Teresa R.', 'McLellan, Jason S.', 'Graham, Barney S.']",,,,
,PMC,Antibody-Induced Conformational Changes in Herpes Simplex Virus Glycoprotein gD Reveal New Targets for Virus Neutralization,http://dx.doi.org/10.1128/JVI.06480-11,PMC3264331,,,"As the receptor-binding protein of herpes simplex virus (HSV), gD plays an essential role in virus entry. In its native state, the last 56 amino acids of the ectodomain C terminus (C-term) occlude binding to its receptors, herpesvirus entry mediator (HVEM) and nectin-1. Although it is clear that movement of the C-term must occur to permit receptor binding, we believe that this conformational change is also a key event for triggering later steps leading to fusion. Specifically, gD mutants containing disulfide bonds that constrain the C-term are deficient in their ability to trigger fusion following receptor binding. In this report, we show that two newly made monoclonal antibodies (MAbs), MC2 and MC5, have virus-neutralizing activity but do not block binding of gD to either receptor. In contrast, all previously characterized neutralizing anti-gD MAbs block binding of gD to a receptor(s). Interestingly, instead of blocking receptor binding, MC2 significantly enhances the affinity of gD for both receptors. Several nonneutralizing MAbs (MC4, MC10, and MC14) also enhanced gD-receptor binding. While MC2 and MC5 recognized different epitopes on the core of gD, these nonneutralizing MAbs recognized the gD C-term. Both the neutralizing capacity and rate of neutralization of virus by MC2 are uniquely enhanced when MC2 is combined with MAb MC4, MC10, or MC14. We suggest that MC2 and MC5 prevent gD from performing a function that triggers later steps leading to fusion and that the epitope for MC2 is normally occluded by the C-term of the gD ectodomain.",,"['Lazear, Eric', 'Whitbeck, J. Charles', 'Ponce-de-Leon, Manuel', 'Cairns, Tina M.', 'Willis, Sharon H.', 'Zuo, Yi', 'Krummenacher, Claude', 'Cohen, Gary H.', 'Eisenberg, Roselyn J.']",,,,
,PMC,Protein sequence analysis based on hydropathy profile of amino acids,http://dx.doi.org/10.1631/jzus.B1100052,PMC3274743,,,"Biology sequence comparison is a fundamental task in computational biology. According to the hydropathy profile of amino acids, a protein sequence is taken as a string with three letters. Three curves of the new protein sequence were defined to describe the protein sequence. A new method to analyze the similarity/dissimilarity of protein sequence was proposed based on the conditional probability of the protein sequence. Finally, the protein sequences of ND6 (NADH dehydrogenase subunit 6) protein of eight species were taken as an example to illustrate the new approach. The results demonstrated that the method is convenient and efficient.",,"['Xie, Xiao-li', 'Zheng, Li-fei', 'Yu, Ying', 'Liang, Li-ping', 'Guo, Man-cai', 'Song, John', 'Yuan, Zhi-fa']",,,,
,PMC,Characterization of the stop codon readthrough signal of Colorado tick fever virus segment 9 RNA,http://dx.doi.org/10.1261/rna.030338.111,PMC3264911,,,"Termination codon readthrough is utilized as a mechanism of expression of a growing number of viral and cellular proteins, but in many cases the mRNA signals that promote readthrough are poorly characterized. Here, we investigated the readthrough signal of Colorado tick fever virus (CTFV) segment 9 RNA (Seg-9). CTFV is the type-species of the genus Coltivirus within the family Reoviridae and is a tick-borne, double-stranded, segmented RNA virus. Seg-9 encodes a 36-kDa protein VP9, and by readthrough of a UGA stop codon, a 65-kDa product, VP9′. Using a reporter system, we defined the minimal sequence requirements for readthrough and confirmed activity in both mammalian and insect cell-free translation systems, and in transfected mammalian cells. Mutational analysis revealed that readthrough was UGA specific, and that the local sequence context around the UGA influenced readthrough efficiency. Readthrough was also dependent upon a stable RNA stem–loop structure beginning eight bases downstream from the UGA codon. Mutational analysis of this stem–loop revealed a requirement for the stem region but not for substructures identified within the loop. Unexpectedly, we were unable to detect a ribosomal pause during translation of the CTFV signal, suggesting that the mechanism of readthrough, at least at this site, is unlikely to be dependent upon RNA secondary-structure induced ribosomal pausing at the recoded stop codon.",,"['Napthine, Sawsan', 'Yek, Christina', 'Powell, Michael L.', 'Brown, T. David K.', 'Brierley, Ian']",,,,
,PMC,A domain-based model for predicting large and complex pseudoknotted structures,http://dx.doi.org/10.4161/rna.18488,PMC3346314,,,"Pseudoknotted structures play important structural and functional roles in RNA cellular functions at the level of transcription, splicing and translation. However, the problem of computational prediction for large pseudoknotted folds remains. Here we develop a domain-based method for predicting complex and large pseudoknotted structures from RNA sequences. The model is based on the observation that large RNAs can be separated into different structural domains. The basic idea is to first identify the domains and then predict the structures for each domain. Assembly of the domain structures gives the full structure. The use of the domain-based approach leads to a reduction of computational time by a factor of about ~N(2) for an N-nt sequence. As applications of the model, we predict structures for a variety of RNA systems, such as regions in human telomerase RNA (hTR), internal ribosome entry site (IRES) and HIV genome. The lengths of these sequences range from 200-nt to 400-nt. The results show good agreements with the experiments.",,"['Cao, Song', 'Chen, Shi-Jie']",,,,
,PMC,CXCL12-Induced Monocyte-Endothelial Interactions Promote Lymphocyte Transmigration Across an in Vitro Blood-Brain Barrier,http://dx.doi.org/10.1126/scitranslmed.3003197,PMC3710123,,,"The accumulation of inflammatory cells in the brain parenchyma is a critical step in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). Chemokines and adhesion molecules orchestrate leukocyte transmigration across the blood-brain barrier (BBB), but the dynamics of chemokine receptor expression during leukocyte transmigration are unclear. We describe an in vitro BBB model system using human brain microvascular endothelial cells that incorporates shear forces mimicking blood flow to elucidate how chemokine receptor expression is modulated during leukocyte transmigration. In the presence of the chemokine CXCL12, we examined modulation of its receptor CXCR4 on human T cells, B cells, and monocytes transmigrating across the BBB under flow conditions. CXCL12 stimulated transmigration of CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes. Transmigration was blocked by CXCR4-neutralizing antibodies. Unexpectedly, CXCL12 selectively down-regulated CXCR4 on transmigrating monocytes, but not T cells. Monocytes underwent preferential CXCL12-mediated adhesion to the BBB in vitro compared with lymphocytes. These findings provide new insights into leukocyte-endothelial interactions at the BBB under conditions mimicking blood flow and suggest that in vitro BBB models may be useful for identifying chemokine receptors that could be modulated therapeutically to reduce neuroinflammation in diseases such as MS.",,"['Man, Shumei', 'Tucky, Barbara', 'Cotleur, Anne', 'Drazba, Judith', 'Takeshita, Yukio', 'Ransohoff, Richard M.']",,,,
,PMC,Development and Application of a High-Throughput Micro-Neutralization Assay - Lack of XMRV/MLV Detection in Blood Donors,http://dx.doi.org/10.1111/j.1537-2995.2011.03519.x,PMC3299481,,,"BACKGROUND: Xenotropic murine leukemia virus (MLV)-related virus (XMRV) and other related MLVs have been described with chronic fatigue syndrome (CFS) and certain types of prostate cancer. In addition, prevalence rates as high as 7% have been reported in blood donors, raising the risk of transfusion-related transmission. Several laboratories have utilized micro-neutralization assays as a surrogate marker for detection of anti-MLV serological responses – with up to 25% of prostate cancer patients reported to harbor neutralizing antibody responses. STUDY DESIGN AND METHODS: We developed a high-throughput micro-neutralization assay for research studies on blood donors using retroviral vectors pseudotyped with XMRV-specific envelopes. Infection with these pseudotypes was neutralized by sera from both macaques and mice challenged with XMRV, but not pre-immune serum. 354 plasma samples from blood donors in the Reno/Tahoe area were screened for neutralization. RESULTS: 6.5% of donor samples gave moderate neutralization of XMRV, but not control pseudotypes. However, further testing by Western blot revealed no evidence of antibodies against MLVs in any of these samples. Furthermore, no evidence of infectious virus or viral nucleic acid was observed. CONCLUSION: A micro-neutralization assay was developed for detection of XMRV, and can be applied in a high-throughput format for large scale studies. Although a proportion of blood donors demonstrated the ability to block XMRV envelope-mediated infection, we found no evidence that this inhibition was mediated by specific antibodies elicited by exposure to XMRV/MLV. It is likely that this moderate neutralization is mediated through another, non-specific mechanism.",,"['Zhou, Yanchen', 'Steffen, Imke', 'Montalvo, Leilani', 'Lee, Tzong-Hae', 'Zemel, Reeve', 'Switzer, William M.', 'Tang, Shaohua', 'Jia, Hongwei', 'Heneine, Walid', 'Winkelman, Valerie', 'Tailor, Chetankumar S.', 'Ikeda, Yasuhiro', 'Simmons, Graham']",,,,
,PMC,Mechanisms of Host Receptor Adaptation by Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1074/jbc.M111.325803,PMC3308800,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) from palm civets has twice evolved the capacity to infect humans by gaining binding affinity for human receptor angiotensin-converting enzyme 2 (ACE2). Numerous mutations have been identified in the receptor-binding domain (RBD) of different SARS-CoV strains isolated from humans or civets. Why these mutations were naturally selected or how SARS-CoV evolved to adapt to different host receptors has been poorly understood, presenting evolutionary and epidemic conundrums. In this study, we investigated the impact of these mutations on receptor recognition, an important determinant of SARS-CoV infection and pathogenesis. Using a combination of biochemical, functional, and crystallographic approaches, we elucidated the molecular and structural mechanisms of each of these naturally selected RBD mutations. These mutations either strengthen favorable interactions or reduce unfavorable interactions with two virus-binding hot spots on ACE2, and by doing so, they enhance viral interactions with either human (hACE2) or civet (cACE2) ACE2. Therefore, these mutations were viral adaptations to either hACE2 or cACE2. To corroborate the above analysis, we designed and characterized two optimized RBDs. The human-optimized RBD contains all of the hACE2-adapted residues (Phe-442, Phe-472, Asn-479, Asp-480, and Thr-487) and possesses exceptionally high affinity for hACE2 but relative low affinity for cACE2. The civet-optimized RBD contains all of the cACE2-adapted residues (Tyr-442, Pro-472, Arg-479, Gly-480, and Thr-487) and possesses exceptionally high affinity for cACE2 and also substantial affinity for hACE2. These results not only illustrate the detailed mechanisms of host receptor adaptation by SARS-CoV but also provide a molecular and structural basis for tracking future SARS-CoV evolution in animals.",,"['Wu, Kailang', 'Peng, Guiqing', 'Wilken, Matthew', 'Geraghty, Robert J.', 'Li, Fang']",,,,
,PMC,Clinical analysis of osteonecrosis of the femoral head induced by steroids,http://dx.doi.org/10.1111/j.1757-7861.2011.00163.x,PMC6583143,,,"Objective:  To explore the clinical characteristics of osteonecrosis of the femoral head (ONFH) induced by steroids. Methods:  From January 2000 to October 2009, 497 hips in 270 cases of ONFH induced by steroids were studied. A questionnaire was administered when the patients were admitted; the questions concerned the underlying disease, duration of steroid usage, total dosage of steroid, incubation period (time interval between commencement of steroid therapy and onset of pain), severity of pain, location of initial complaint, primary diagnosis, time lag from onset of pain to final diagnosis and physical signs when admitted. The correlations between pain and Association Research Circulation Osseous (ARCO) stage, bone marrow edema (BME) and lesion size were analyzed. Results:  The median of time between commencing steroid medication and developing ONFH for the 269 cases was 18 months (range, 2–384 months). 78.82% cases presented with pain within three years of steroid initiation, only 10.41% patients first complained of pain six or more years after commencing steroid therapy. Fifty‐six cases (20.82%) were misdiagnosed, lumbar disorders being the most frequent misdiagnoses. 79.29% of symptomatic hips presented with abnormal physical tests. Of 420 symptomatic hips, 166 hips were type C1, 223 hips type C2; 299 hips had collapsed; and there was BME in 209 hips. Conclusion:  Most patients with ONFH induced by steroids complained of pain within 3 years of commencing steroid therapy. Pain was associated with lesion size, collapse and BME. Atypical location of pain, failure to perform a physical examination and MRI findings were the main causes of misdiagnoses.",,"['Zhao, Feng‐chao', 'Li, Zi‐rong', 'Guo, Kai‐jin']",,,,
,PMC,Hiding the evidence: two strategies for innate immune evasion by hemorrhagic fever viruses,http://dx.doi.org/10.1016/j.coviro.2012.01.003,PMC3758253,,,"The innate immune system is one of the first lines of defense against invading pathogens. Pathogens have, in turn, evolved different strategies to counteract these responses. Recent studies have illuminated how the hemorrhagic fever viruses Ebola and Lassa fever prevent host sensing of double-stranded RNA (dsRNA), a key hallmark of viral infection. The ebolavirus protein VP35 adopts a unique bimodal configuration to mask key cellular recognition sites on dsRNA. Conversely, the Lassa fever virus nucleoprotein, NP, actually digests the dsRNA signature. Collectively, these structural and functional studies shed new light on the mechanisms of pathogenesis of these viruses and provide new targets for therapeutic intervention.",,"['Hastie, Kathryn M.', 'Bale, Shridhar', 'Kimberlin, Christopher R.', 'Saphire, Erica Ollmann']",,,,
,PMC,Economic Analysis of the Use of Facemasks During Pandemic (H1N1) 2009,http://dx.doi.org/10.1016/j.jtbi.2012.01.032,PMC3307882,,,"A large-scale pandemic could cause severe health, social, and economic impacts. The recent 2009 H1N1 pandemic confirmed the need for mitigation strategies that are cost-effective and easy to implement. Typically, in the early stages of a pandemic, as seen with pandemic (H1N1) 2009, vaccines and antivirals may be limited or non-existent, resulting in the need for non-pharmaceutical strategies to reduce the spread of disease and the economic impact. We construct and analyze a mathematical model for a population comprised of three different age groups and assume that some individuals wear facemasks. We then quantify the impact facemasks could have had on the spread of pandemic (H1N1) 2009 and examine their cost effectiveness. Our analyses show that an unmitigated pandemic could result in losses of nearly $832 billion in the United States during the length of the pandemic. Based on present value of future earnings, hospital costs, and lost income estimates due to illness, this study estimates that the use of facemasks by 10%, 25%, and 50% of the population could reduce economic losses by $478 billion, $570 billion, and $573 billion, respectively. The results show that facemasks can significantly reduce the number of influenza cases as well as the economic losses due to a pandemic.",,"['Tracht, Samantha M.', 'Del Valle, Sara Y.', 'Edwards, Brian K.']",,,,
,PMC,Single Chain MHC I trimer-based DNA vaccines for protection against Listeria monocytogenes infection,http://dx.doi.org/10.1016/j.vaccine.2012.01.012,PMC3288962,,,"To circumvent limitations of poor antigen presentation and immunogenicity of DNA vaccines that target induction of CD8(+) T cell immunity, we have generated single chain MHC I trimers (MHC I SCTs) composed of a single polypeptide chain with a linear composition of antigenic peptide, β2-microglobulin, and heavy chain of a MHC class I molecule connected by flexible linkers. Because of its pre-assembled nature, the SCT presents enhanced expression and presentation of the antigenic peptide/MHC complexes at the cell surface. Furthermore, DNA vaccination with a plasmid DNA encoding an SCT incorporating an immunodominant viral epitope elicited protective CD8(+) T cell responses against lethal virus infection. To extend these findings, here we tested the efficacy of SCT DNA vaccines against bacterial infections. In a mouse infection model of Listeria monocytogenes, the SCT DNA vaccine encoding H-2K(d) and the immunodominant peptide LLO 91–99 generated functional primary and memory peptide-specific CD8(+) T cells that confer partial protection against L. monocytogenes infection. DNA immunization of K(d)/LLO(91–99) SCTs generated functional memory CD8(+) T cells independently of CD4(+) T cells, although the expression of cognate or non-cognate CD4(+) helper T cell epitopes further enhanced the protective efficacy of SCTs. Our study further demonstrates that the SCT serves as a potent platform for DNA vaccines against various infectious diseases.",,"['Kim, Sojung', 'Zuiani, Adam', 'Carrero, Javier A.', 'Hansen, Ted H.']",,,,
,PMC,ENaCs and ASICs as therapeutic targets,http://dx.doi.org/10.1152/ajpcell.00019.2012,PMC3330738,,,"The epithelial Na(+) channel (ENaC) and acid-sensitive ion channel (ASIC) branches of the ENaC/degenerin superfamily of cation channels have drawn increasing attention as potential therapeutic targets in a variety of diseases and conditions. Originally thought to be solely expressed in fluid absorptive epithelia and in neurons, it has become apparent that members of this family exhibit nearly ubiquitous expression. Therapeutic opportunities range from hypertension, due to the role of ENaC in maintaining whole body salt and water homeostasis, to anxiety disorders and pain associated with ASIC activity. As a physiologist intrigued by the fundamental mechanics of salt and water transport, it was natural that Dale Benos, to whom this series of reviews is dedicated, should have been at the forefront of research into the amiloride-sensitive sodium channel. The cloning of ENaC and subsequently the ASIC channels has revealed a far wider role for this channel family than was previously imagined. In this review, we will discuss the known and potential roles of ENaC and ASIC subunits in the wide variety of pathologies in which these channels have been implicated. Some of these, such as the role of ENaC in Liddle's syndrome are well established, others less so; however, all are related in that the fundamental defect is due to inappropriate channel activity.",,"['Qadri, Yawar J.', 'Rooj, Arun K.', 'Fuller, Catherine M.']",,,,
,PMC,Estimating Absolute and Relative Case Fatality Ratios from Infectious Disease Surveillance Data,http://dx.doi.org/10.1111/j.1541-0420.2011.01709.x,PMC4540071,,,"Knowing which populations are most at risk for severe outcomes from an emerging infectious disease is crucial in deciding the optimal allocation of resources during an outbreak response. The case fatality ratio (CFR) is the fraction of cases that die after contracting a disease. The relative CFR is the factor by which the case fatality in one group is greater or less than that in a second group. Incomplete reporting of the number of infected individuals, both recovered and dead, can lead to biased estimates of the CFR. We define conditions under which the CFR and the relative CFR are identifiable. Furthermore, we propose an estimator for the relative CFR that controls for time-varying reporting rates. We generalize our methods to account for elapsed time between infection and death. To demonstrate the new methodology, we use data from the 1918 influenza pandemic to estimate relative CFRs between counties in Maryland. A simulation study evaluates the performance of the methods in outbreak scenarios. An R software package makes the methods and data presented here freely available. Our work highlights the limitations and challenges associated with estimating absolute and relative CFRs in practice. However, in certain situations, the methods presented here can help identify vulnerable subpopulations early in an outbreak of an emerging pathogen such as pandemic influenza.",,"['Reich, Nicholas G.', 'Lessler, Justin', 'Cummings, Derek A. T.', 'Brookmeyer, Ron']",,,,
,PMC,"H5N1 influenza viruses: Facts, not fear",http://dx.doi.org/10.1073/pnas.1121297109,PMC3289294,,,"The ongoing controversy over publication of two studies involving the transmission in ferrets of H5N1 (H5) subtype influenza viruses and the recommendations of the National Science Advisory Board for Biosecurity to redact key details in the manuscripts call for an examination of relevant scientific facts. In addition, there are calls in the media to destroy the viruses, curtail future research in this area, and protect the public from such “frightening” research efforts. Fear needs to be put to rest with solid science and not speculation.",,"['Palese, Peter', 'Wang, Taia T.']",,,,
,PMC,Proteomic Analysis of Sulfolobus solfataricus During Sulfolobus Turreted Icosahedral Virus Infection,http://dx.doi.org/10.1021/pr201087v,PMC3339632,,,"Where there is life, there are viruses. The impact of viruses on evolution, global nutrient cycling, and disease has driven research on their cellular and molecular biology. Knowledge exists for a wide range of viruses, however, a major exception are viruses with archaeal hosts. Archaeal virus-host systems are of great interest because they have similarities to both eukaryotic and bacterial systems and often live in extreme environments. Here we report the first proteomics-based experiments on archaeal host response to viral infection. Sulfolobus Turreted Icosahedral Virus (STIV) infection of Sulfolobus solfataricus P2 was studied using 1D and 2D differential gel electrophoresis (DIGE) to measure abundance and redox changes. Cysteine reactivity was measured using novel fluorescent zwitterionic chemical probes that, together with abundance changes, suggest that virus and host are both vying for control of redox status in the cells. Proteins from nearly 50% of the predicted viral open reading frames were found along with a new STIV protein with a homolog in STIV2. This study provides insight to features of viral replication novel to the archaea, makes strong connections to well described mechanisms used by eukaryotic viruses such as ESCRT-III mediated transport, and emphasizes the complementary nature of different omics approaches.",,"['Maaty, Walid S.', 'Selvig, Kyla', 'Ryder, Stephanie', 'Tarlykov, Pavel', 'Hilmer, Jonathan K.', 'Heinemann, Joshua', 'Steffens, Joseph', 'Snyder, Jamie C.', 'Ortmann, Alice C.', 'Movahed, Navid', 'Spicka, Kevin', 'Chetia, Lakshindra', 'Grieco, Paul A.', 'Dratz, Edward A.', 'Douglas, Trevor', 'Young, Mark J.', 'Bothner, Brian']",,,,
,PMC,"A Randomized, Controlled Trial of Panax quinquefolius extract (CVT-E002) to Reduce Respiratory Infection in Patients with Chronic Lymphocytic Leukemia",http://dx.doi.org/10.1016/j.suponc.2011.10.005,PMC3337952,,,"BACKGROUND: Chronic Lymphocytic Leukemia (CLL) patients are at high risk for acute respiratory illness (ARI). OBJECTIVE: Evaluate safety/efficacy of a proprietary extract of Panax quinequefolius, CVT-E002 (Afexa Life Sciences) to reduce ARI. METHODS: Double-blind, placebo-controlled, randomized trial:293 subjects with early-stage, untreated CLL January-March, 2009. RESULTS: ARI days were common occurring on about 10% of days during the study period. There were no significant differences of the two a priori primary endpoints: ARI days (8.5 ± 17.2 for CVT-E002 vs. 6.8 ± 13.3 for placebo) or severe ARI days (2.9 ± 9.5 for CVT-E002 vs. 2.6 ± 9.8 for placebo). However, 51% percent of CVT-E002 vs. 56% of placebo recipients experienced at least one ARI (diff -5%, 95% C.I. -16%,7%); more intense ARI occurred in 32% of CVT-E002 vs. 39% of placebo recipients (diff -7%, 95% C.I. -18%, 4%), and symptom-specific evaluation showed reduced moderate-severe sore throat (p = 0.004) and a lower rate of grade ≥3 toxicities (p = 0.02) in CVT-E002 recipients. Greater seroconversion (4-fold increases in antibody titer) vs. 9 common viral pathogens was documented in CVT-E002 recipients (16% vs. 7%; p = 0.04). LIMITATIONS: Serologic evaluation of antibody titers were not tied to a specific illness, but evaluated over the entire study period. CONCLUSION: CVT-E002 was well tolerated.CVT-E002 did not reduce the number of ARI days or antibiotic use; however, there was a trend toward reduced rates of moderate-severe ARI and significantly less sore throat, suggesting the increased rate of seroconversion most likely reflects CVT-E002-enhanced antibody responses.",,"['High, Kevin P.', 'Case, Doug', 'Hurd, David', 'Powell, Bayard', 'Lesser, Glenn', 'Falsey, Ann R.', 'Siegel, Robert', 'Metzner-Sadurski, Joanna', 'Krauss, John C.', 'Chinnasami, Bernard', 'Sanders, George', 'Rousey, Steven', 'Shaw, Edward G.']",,,,
,PMC,Expanding roles for CD4(+) T cells in immunity to viruses,http://dx.doi.org/10.1038/nri3152,PMC3764486,,,"Viral pathogens often generate strong CD4(+) T cell responses that are best known for their ability to help B cell and CD8(+) T cell responses. However, recent studies reveal additional roles for CD4(+) T cells, some of which are independent of other lymphocytes, and indicate that memory cells are more effective in most functions than naïve CD4 T cells. Here, we review the full spectrum of antiviral functions of CD4(+) T cells, including their helper activities, innate immune induction, and direct anti-viral roles, and suggest how these functions are integrated to provide highly protective responses against viral pathogens.",,"['Swain, Susan L.', 'McKinstry, K. Kai', 'Strutt, Tara M.']",,,,
,PMC,Reducing agents affect inhibitory activities of compounds: Results from Multiple Drug Targets,http://dx.doi.org/10.1016/j.ab.2012.01.006,PMC3299889,,,"High-throughput screening (HTS) of large compound libraries has become a commonly used method for the identification of drug leads, and non-physiological reducing agents have been widely used for HTS. However, a comparison of the difference in the HTS results based on the choice of reducing agent used and potency comparisons of selected inhibitors has not been done with the physiological reducing agent, reduced glutathione (GSH). Here, we compared the effects of three reducing agents: dithiothreitol (DTT), β-mercaptoethanol (β-MCE), and tris-(2-carboxyethyl)-phosphine (TCEP), in addition to GSH, against three drug target proteins. Approximately 100,000 compounds were computationally screened for each target protein, and experimental testing of high scoring compounds (~560 compounds) with the four reducing agents surprisingly produced many non-overlapping hits. More importantly, we find that various reducing agents alter inhibitor potency (IC(50)) from ~10 µM with one reducing agent to complete loss (IC(50) > 200 µM) of inhibitory activity with another reducing agent. Therefore, the choice of reducing agent in a HTS is critical as this may lead to the pursuit of falsely identified active compounds or failure to identify the true active compounds. We demonstrate the feasibility of using GSH for in vitro HTS assays with these three target enzymes.",,"['Lee, Hyun', 'Torres, Jaime', 'Truong, Lena', 'Chaudhuri, Rima', 'Mittal, Anuradha', 'Johnson, Michael E.']",,,,
,PMC,Phosphatidylinositol 4-Kinase IIIβ Is Required for Severe Acute Respiratory Syndrome Coronavirus Spike-mediated Cell Entry,http://dx.doi.org/10.1074/jbc.M111.312561,PMC3318727,,,"Phosphatidylinositol kinases (PI kinases) play an important role in the life cycle of several viruses after infection. Using gene knockdown technology, we demonstrate that phosphatidylinositol 4-kinase IIIβ (PI4KB) is required for cellular entry by pseudoviruses bearing the severe acute respiratory syndrome-coronavirus (SARS-CoV) spike protein and that the cell entry mediated by SARS-CoV spike protein is strongly inhibited by knockdown of PI4KB. Consistent with this observation, pharmacological inhibitors of PI4KB blocked entry of SARS pseudovirions. Further research suggested that PI4P plays an essential role in SARS-CoV spike-mediated entry, which is regulated by the PI4P lipid microenvironment. We further demonstrate that PI4KB does not affect virus entry at the SARS-CoV S-ACE2 binding interface or at the stage of virus internalization but rather at or before virus fusion. Taken together, these results indicate a new function for PI4KB and suggest a new drug target for preventing SARS-CoV infection.",,"['Yang, Ning', 'Ma, Ping', 'Lang, Jianshe', 'Zhang, Yanli', 'Deng, Jiejie', 'Ju, Xiangwu', 'Zhang, Gongyi', 'Jiang, Chengyu']",,,,
,PMC,"Expression of the C-type lectins DC-SIGN or L-SIGN alters host cell susceptibility for the avian coronavirus, infectious bronchitis virus",http://dx.doi.org/10.1016/j.vetmic.2012.01.011,PMC3600652,,,"Infectious bronchitis virus (IBV), an avian coronavirus, is a cause of great economic loss in the poultry industry. The virus mainly infects respiratory epithelium, but can be also detected in other organs. The functional receptor for the virus has not been found and field strains of IBV do not infect conventional cell lines. Recently, it has been shown that the C-type lectins DC-SIGN/L-SIGN can promote entry of several coronaviruses. Here we examine whether DC-SIGN/L-SIGN are entry determinants for IBV. We show that by introducing human DC-SIGN/L-SIGN into non-permissive cells, infection by the IBV is dramatically increased. DC-SIGN mediated infection was inhibited by mannan and anti-lectin antibodies, and was independent of sialic acid levels on the cell. Enhancement of IBV infection also occurred for different serotypes of IBV. Our findings demonstrated that even in the absence of avian-specific receptor, DC-SIGN-like lectins are capable of mediating efficient IBV infection.",,"['Zhang, Yueting', 'Buckles, Elizabeth', 'Whittaker, Gary R.']",,,,
,PMC,Effective virus inactivation and removal by steps of Biotest Pharmaceuticals IGIV production process,http://dx.doi.org/10.1016/j.rinim.2012.01.002,PMC3862342,,,"The virus validation of three steps of Biotest Pharmaceuticals IGIV production process is described here. The steps validated are precipitation and removal of fraction III of the cold ethanol fractionation process, solvent/detergent treatment and 35 nm virus filtration. Virus validation was performed considering combined worst case conditions. By these validated steps sufficient virus inactivation/removal is achieved, resulting in a virus safe product.",,"['Dichtelmüller, Herbert O.', 'Flechsig, Eckhard', 'Sananes, Frank', 'Kretschmar, Michael', 'Dougherty, Christopher J.']",,,,
,PMC,Translational research in infectious disease: current paradigms and challenges ahead,http://dx.doi.org/10.1016/j.trsl.2011.12.009,PMC3361696,,,"In recent years, the biomedical community has witnessed a rapid scientific and technological evolution following the development and refinement of high-throughput methodologies. Concurrently and consequentially, the scientific perspective has changed from the reductionist approach of meticulously analyzing the fine details of a single component of biology, to the “holistic” approach of broadmindedly examining the globally interacting elements of biological systems. The emergence of this new way of thinking has brought about a scientific revolution in which genomics, proteomics, metabolomics and other “omics” have become the predominant tools by which large amounts of data are amassed, analyzed and applied to complex questions of biology that were previously unsolvable. This enormous transformation of basic science research and the ensuing plethora of promising data, especially in the realm of human health and disease, have unfortunately not been followed by a parallel increase in the clinical application of this information. On the contrary, the number of new potential drugs in development has been steadily decreasing, suggesting the existence of roadblocks that prevent the translation of promising research into medically relevant therapeutic or diagnostic application. In this paper we will review, in a non-inclusive fashion, several recent scientific advancements in the field of translational research, with a specific focus on how they relate to infectious disease. We will also present a current picture of the limitations and challenges that exist for translational research, as well as ways that have been proposed by the National Institutes of Health to improve the state of this field.",,"['Fontana, Judith M.', 'Alexander, Elizabeth', 'Salvatore, Mirella']",,,,
,PMC,Functional Transcriptional Regulatory Sequence (TRS) RNA Binding and Helix Destabilizing Determinants of Murine Hepatitis Virus (MHV) Nucleocapsid (N) Protein,http://dx.doi.org/10.1074/jbc.M111.287763,PMC3293523,,,"Coronavirus (CoV) nucleocapsid (N) protein contains two structurally independent RNA binding domains. These are denoted N-terminal domain (NTD) and C-terminal domain and are joined by a charged linker region rich in serine and arginine residues (SR linker). In mouse hepatitis virus (MHV), the NTD binds the transcriptional regulatory sequence (TRS) RNA, a conserved hexanucleotide sequence required for subgenomic RNA synthesis. The NTD is also capable of disrupting a short RNA duplex. We show here that three residues on the β3 (Arg-125 and Tyr-127) and β5 (Tyr-190) strands play key roles in TRS RNA binding and helix destabilization with Ala substitutions of these residues lethal to the virus. NMR studies of the MHV NTD·TRS complex revealed that this region defines a major RNA binding interface in MHV with site-directed spin labeling studies consistent with a model in which the adenosine-rich 3′-region of TRS is anchored by Arg-125, Tyr-127, and Tyr-190 in a way that is critical for efficient subgenomic RNA synthesis in MHV. Characterization of CoV N NTDs from infectious bronchitis virus and from severe acute respiratory syndrome CoV revealed that, although detailed NTD-TRS determinants are distinct from those of MHV NTD, rapid helix destabilization activity of CoV N NTDs is most strongly correlated with CoV function and virus viability.",,"['Keane, Sarah C.', 'Liu, Pinghua', 'Leibowitz, Julian L.', 'Giedroc, David P.']",,,,
,PMC,Short Message Service (SMS) Applications for Disease Prevention in Developing Countries,http://dx.doi.org/10.2196/jmir.1823,PMC3846341,22262730,CC BY,"BACKGROUND: The last decade has witnessed unprecedented growth in the number of mobile phones in the developing world, thus linking millions of previously unconnected people. The ubiquity of mobile phones, which allow for short message service (SMS), provides new and innovative opportunities for disease prevention efforts. OBJECTIVE: The aim of this review was to describe the characteristics and outcomes of SMS interventions for disease prevention in developing countries and provide recommendations for future work. METHODS: A systematic search of peer-reviewed and gray literature was performed for papers published in English, French, and German before May 2011 that describe SMS applications for disease prevention in developing countries. RESULTS: A total of 34 SMS applications were described, among which 5 had findings of an evaluation reported. The majority of SMS applications were pilot projects in various levels of sophistication; nearly all came from gray literature sources. Many applications were initiated by the project with modes of intervention varying between one-way or two-way communication, with or without incentives, and with educative games. Evaluated interventions were well accepted by the beneficiaries. The primary barriers identified were language, timing of messages, mobile network fluctuations, lack of financial incentives, data privacy, and mobile phone turnover. CONCLUSION: This review illustrates that while many SMS applications for disease prevention exist, few have been evaluated. The dearth of peer-reviewed studies and the limited evidence found in this systematic review highlight the need for high-quality efficacy studies examining behavioral, social, and economic outcomes of SMS applications and mobile phone interventions aimed to promote health in developing country contexts.",2012 Jan 12,"['Déglise, Carole', 'Suggs, L. Suzanne', 'Odermatt, Peter']",J Med Internet Res,,,
,PMC,"Immune-mediated Loss of Transgene Expression From Virally Transduced Brain Cells Is Irreversible, Mediated by IFNγ, Perforin, and TNFα, and due to the Elimination of Transduced Cells",http://dx.doi.org/10.1038/mt.2011.243,PMC3321600,,,"The adaptive immune response to viral vectors reduces vector-mediated transgene expression from the brain. It is unknown, however, whether this loss is caused by functional downregulation of transgene expression or death of transduced cells. Herein, we demonstrate that during the elimination of transgene expression, the brain becomes infiltrated with CD4(+) and CD8(+) T cells and that these T cells are necessary for transgene elimination. Further, the loss of transgene-expressing brain cells fails to occur in the absence of IFNγ, perforin, and TNFα receptor. Two methods to induce severe immune suppression in immunized animals also fail to restitute transgene expression, demonstrating the irreversibility of this process. The need for cytotoxic molecules and the irreversibility of the reduction in transgene expression suggested to us that elimination of transduced cells is responsible for the loss of transgene expression. A new experimental paradigm that discriminates between downregulation of transgene expression and the elimination of transduced cells demonstrates that transduced cells are lost from the brain upon the induction of a specific antiviral immune response. We conclude that the anti-adenoviral immune response reduces transgene expression in the brain through loss of transduced cells.",,"['Zirger, Jeffrey M', 'Puntel, Mariana', 'Bergeron, Josee', 'Wibowo, Mia', 'Moridzadeh, Rameen', 'Bondale, Niyati', 'Barcia, Carlos', 'Kroeger, Kurt M', 'Liu, Chunyan', 'Castro, Maria G', 'Lowenstein, Pedro R']",,,,
,PMC,T helper cell- and CD40-dependent germline IgM prevents chronic virus-induced demyelinating disease,http://dx.doi.org/10.1073/pnas.1115154109,PMC3268283,,,"Generation of antiviral IgM is usually considered as a marker of a short-lived initial antibody response that is replaced by hypermutated and more-efficient IgG. However, once viruses have established a particular niche for their persistence (e.g., within the CNS), the immune system has to specifically mobilize a broad range of antimicrobial effectors to contain the pathogen in the long term. Infection of the CNS with the mouse hepatitis virus (MHV) provides a unique model situation in which the extent of inflammatory CNS disease is determined by the balance between antiviral immune control, viral replication, and immune-mediated damage. We show here that whereas antibody- or B cell-deficient mice failed to contain MHV CNS infection and developed progressive demyelinating disease, germline IgM produced in activation-induced cytidine deaminase-deficient mice (aicda(−/−)) provided long-term protection against the chronic multiple sclerosis-like disease. Furthermore, we found that appropriate B-cell activation within the CNS-draining lymph node and subsequent CXCR3-mediated migration of antiviral IgM-secreting cells to the infected CNS was dependent on CD40-mediated interaction of B cells with T helper cells. These data indicate that the CD40-mediated collaboration of T and B cells is critical to secure neuroprotective IgM responses during viral CNS infection.",,"['Gil-Cruz, Cristina', 'Perez-Shibayama, Christian', 'Firner, Sonja', 'Waisman, Ari', 'Bechmann, Ingo', 'Thiel, Volker', 'Cervantes-Barragan, Luisa', 'Ludewig, Burkhard']",,,,
,PMC,Signaling by myeloid C-type lectin receptors in immunity and homeostasis,http://dx.doi.org/10.1146/annurev-immunol-031210-101352,PMC4480235,,,"Myeloid cells are key drivers of physiological responses to pathogen invasion or tissue damage. Members of the C-type lectin receptor (CLR) family stand out among the specialized receptors utilized by myeloid cells to orchestrate these responses. CLR ligands include carbohydrate, protein and lipid components of both pathogens and self, which variably trigger endocytic, phagocytic, pro-inflammatory or anti-inflammatory reactions. These varied outcomes rely on a versatile system for CLR signaling that includes tyrosine based motifs that recruit kinases, phosphatases or endocytic adaptors, as well as non-tyrosine based signals that modulate the activation of other pathways or couple to the uptake machinery. Here, we review the signaling properties of myeloid CLRs and how they impact the role of myeloid cells in innate and adaptive immunity.",,"['Sancho, David', 'Reis e Sousa, Caetano']",,,,
,PMC,Phylogeography and Population Dynamics of Dengue Viruses in the Americas,http://dx.doi.org/10.1093/molbev/msr320,PMC3529620,,,"Changes in Dengue virus (DENV) disease patterns in the Americas over recent decades have been attributed, at least in part, to repeated introduction of DENV strains from other regions, resulting in a shift from hypoendemicity to hyperendemicity. Using newly sequenced DENV-1 and DENV-3 envelope (E) gene isolates from 11 Caribbean countries, along with sequences available on GenBank, we sought to document the population genetic and spatiotemporal transmission histories of the four main invading DENV genotypes within the Americas and investigate factors that influence the rate and intensity of DENV transmission. For all genotypes, there was an initial invasion phase characterized by rapid increases in genetic diversity, which coincided with the first confirmed cases of each genotype in the region. Rapid geographic dispersal occurred upon each genotype's introduction, after which individual lineages were locally maintained, and gene flow was primarily observed among neighboring and nearby countries. There were, however, centers of viral diversity (Barbados, Puerto Rico, Colombia, Suriname, Venezuela, and Brazil) that were repeatedly involved in gene flow with more distant locations. For DENV-1 and DENV-2, we found that a “distance-informed” model, which posits that the intensity of virus movement between locations is inversely proportional to the distance between them, provided a better fit than a model assuming equal rates of movement between all pairs of countries. However, for DENV-3 and DENV-4, the more stochastic “equal rates” model was preferred.",,"['Allicock, Orchid M.', 'Lemey, Philippe', 'Tatem, Andrew J.', 'Pybus, Oliver G.', 'Bennett, Shannon N.', 'Mueller, Brandi A.', 'Suchard, Marc A.', 'Foster, Jerome E.', 'Rambaut, Andrew', 'Carrington, Christine V. F.']",,,,
,PMC,Induction of DNA Damage Signaling upon Rift Valley Fever Virus Infection Results in Cell Cycle Arrest and Increased Viral Replication,http://dx.doi.org/10.1074/jbc.M111.296608,PMC3293538,,,"Rift Valley fever virus (RVFV) is a highly pathogenic arthropod-borne virus infecting a wide range of vertebrate hosts. Of particular interest is the nonstructural NSs protein, which forms large filamentous fibril bundles in the nucleus. Past studies have shown NSs to be a multifaceted protein important for virulence through modulation of the interferon response as well acting as a general inhibitor of transcription. Here we investigated the regulation of the DNA damage signaling cascades by RVFV infection and found virally inducted phosphorylation of the classical DNA damage signaling proteins, ataxia-telangiectasia mutated (ATM) (Ser-1981), Chk.2 (Thr-68), H2A.X (Ser-139), and p53 (Ser-15). In contrast, ataxia-telangiectasia mutated and Rad3-related kinase (ATR) (Ser-428) phosphorylation was decreased following RVFV infection. Importantly, both the attenuated vaccine strain MP12 and the fully virulent strain ZH548 showed strong parallels in their up-regulation of the ATM arm of the DNA damage response and in the down-regulation of the ATR pathway. The increase in DNA damage signaling proteins did not result from gross DNA damage as no increase in DNA damage was observed following infection. Rather the DNA damage signaling was found to be dependent on the viral protein NSs, as an NSs mutant virus was not found to induce the equivalent signaling pathways. RVFV MP12-infected cells also displayed an S phase arrest that was found to be dependent on NSs expression. Use of ATM and Chk.2 inhibitors resulted in a marked decrease in S phase arrest as well as viral production. These results indicate that RVFV NSs induces DNA damage signaling pathways that are beneficial for viral replication.",,"['Baer, Alan', 'Austin, Dana', 'Narayanan, Aarthi', 'Popova, Taissia', 'Kainulainen, Markus', 'Bailey, Charles', 'Kashanchi, Fatah', 'Weber, Friedemann', 'Kehn-Hall, Kylene']",,,,
,PMC,Environmental Factors Affecting the Transmission of Respiratory Viruses,http://dx.doi.org/10.1016/j.coviro.2011.12.003,PMC3311988,,,"Many viruses are capable of infecting the human respiratory tract to cause disease. These viruses display various transmission patterns among humans; however, they all share the ability to transmit from person to person, and their human transmissibility is influenced by the environment in which pathogen and host meet. This review aims to summarize recent and significant observations regarding the impact of environmental factors such as weather and climate, humidity, temperature, and airflow on the transmission of human respiratory viruses. Where possible, knowledge gaps that require further scientific study will be identified.",,"['Pica, Natalie', 'Bouvier, Nicole M.']",,,,
,PMC,Molecular Determinants of Enterovirus 71 Viral Entry: CLEFT AROUND GLN-172 ON VP1 PROTEIN INTERACTS WITH VARIABLE REGION ON SCAVENGE RECEPTOR B 2,http://dx.doi.org/10.1074/jbc.M111.301622,PMC3307280,,,"Enterovirus 71 (EV71) is one of the major pathogens that cause hand, foot, and mouth disease outbreaks in young children in the Asia-Pacific region in recent years. Human scavenger receptor class B 2 (SCARB2) is the main cellular receptor for EV71 on target cells. The requirements of the EV71-SCARB2 interaction have not been fully characterized, and it has not been determined whether SCARB2 serves as an uncoating receptor for EV71. Here we compared the efficiency of the receptor from different species including human, horseshoe bat, mouse, and hamster and demonstrated that the residues between 144 and 151 are critical for SCARB2 binding to viral capsid protein VP1 of EV71 and seven residues from the human receptor could convert murine SCARB2, an otherwise inefficient receptor, to an efficient receptor for EV71 viral infection. We also identified that EV71 binds to SCARB2 via a canyon of VP1 around residue Gln-172. Soluble SCARB2 could convert the EV71 virions from 160 S to 135 S particles, indicating that SCARB2 is an uncoating receptor of the virus. The uncoating efficiency of SCARB2 significantly increased in an acidic environment (pH 5.6). These studies elucidated the viral capsid and receptor determinants of enterovirus 71 infection and revealed a possible target for antiviral interventions.",,"['Chen, Pan', 'Song, Zilin', 'Qi, Yonghe', 'Feng, Xiaofeng', 'Xu, Naiqing', 'Sun, Yinyan', 'Wu, Xing', 'Yao, Xin', 'Mao, Qunyin', 'Li, Xiuling', 'Dong, Wenjuan', 'Wan, Xiaobo', 'Huang, Niu', 'Shen, Xinliang', 'Liang, Zhenglun', 'Li, Wenhui']",,,,
,PMC,Principles of Virus Structural Organization,http://dx.doi.org/10.1007/978-1-4614-0980-9_3,PMC3767311,,,"Viruses, the molecular nanomachines infecting hosts ranging from prokaryotes to eukaryotes, come in different sizes, shapes and symmetries. Questions such as what principles govern their structural organization, what factors guide their assembly, how these viruses integrate multifarious functions into one unique structure have enamored researchers for years. In the last five decades, following Caspar and Klug's elegant conceptualization of how viruses are constructed, high resolution structural studies using X-ray crystallography and more recently cryo-EM techniques have provided a wealth of information on structures of variety of viruses. These studies have significantly furthered our understanding of the principles that underlie structural organization in viruses. Such an understanding has practical impact in providing a rational basis for the design and development of antiviral strategies. In this chapter, we review principles underlying capsid formation in a variety of viruses, emphasizing the recent developments along with some historical perspective.",,"['Prasad, B.V. Venkataram', 'Schmid, Michael F']",,,,
,PMC,Applications of Functional Protein Microarrays in Basic and Clinical Research,http://dx.doi.org/10.1016/B978-0-12-394395-8.00004-9,PMC3790149,,,"The protein microarray technology provides a versatile platform for characterization of hundreds of thousands of proteins in a highly parallel and high-throughput manner. It is viewed as a new tool that overcomes the limitation of DNA microarrays. On the basis of its application, protein microarrays fall into two major classes: analytical and functional protein microarrays. In addition, tissue or cell lysates can also be directly spotted on a slide to form the so-called “reverse-phase” protein microarray. In the last decade, applications of functional protein microarrays in particular have flourished in studying protein function and construction of networks and pathways. In this chapter, we will review the recent advancements in the protein microarray technology, followed by presenting a series of examples to illustrate the power and versatility of protein microarrays in both basic and clinical research. As a powerful technology platform, it would not be surprising if protein microarrays will become one of the leading technologies in proteomic and diagnostic fields in the next decade.",,"['Zhu, Heng', 'Qian, Jiang']",,,,
,PMC,Molecular Modeling of Inhibitors of Human DNA Methyltransferase with a Crystal Structure: Discovery of a Novel DNMT1 inhibitor,http://dx.doi.org/10.1016/B978-0-12-398312-1.00008-1,PMC3837394,,,"DNA methyltransferases (DNMTs) are promising epigenetic targets for the development of novel anticancer drugs and other diseases. Molecular modeling and experimental approaches are being used to identify and develop inhibitors of human DNMTs. Most of the computational efforts conducted so far with DNMT1 employ homology models of the enzyme. Recently, a crystallographic structure of the methyltransferase domain of human DNMT1 bound to unmethylated DNA was published. Following on our previous computational and experimental studies with DNMTs, we herein present molecular dynamics of the crystal structure of human DNMT1. Docking studies of established DNMT1 inhibitors with the crystal structure gave rise to a structure-based pharmacophore model that suggests key interactions of the inhibitors with the catalytic binding site. Results had a good agreement with the docking and pharmacophore models previously developed using a homology model of the catalytic domain of DNMT1. The docking protocol was able to distinguish active DNMT1 inhibitors from, for example, experimentally known inactive DNMT1 inhibitors. As part of our efforts to identify novel inhibitors of DNMT1, we conducted the experimental characterization of aurintricarboxylic acid (ATA) that in preliminary docking studies showed promising activity. ATA had a sub-micromolar inhibition (IC(50) = 0.68 μM) against DNMT1. ATA was also evaluated for Dnmt3a inhibition showing an IC(50) = 1.4 μM. This chapter illustrates the synergy from integrating molecular modeling and experimental methods for further advance the discovery of novel candidates for epigenetic therapies.",,"['Yoo, Jakyung', 'Kim, Joo Hee', 'Robertson, Keith D.', 'Medina-Franco, José L.']",,,,
,PMC,Changing Perceptions: of Pandemic Influenza and Public Health Responses,http://dx.doi.org/10.2105/AJPH.2011.300330,PMC3490545,,,"According to the latest World Bank estimates, over the past decade some US $4.3 billion has been pledged by governments to combat the threat of pandemic influenza. Presidents, prime ministers, and even dictators the world over have been keen to demonstrate their commitment to tackling this disease, but this has not always been the case. Indeed, government-led intervention in responding to the threat of pandemic influenza is a relatively recent phenomenon. I explore how human understandings of influenza have altered over the past 500 years and how public policy responses have shifted accordingly. I trace the progress in human understanding of causation from meteorological conditions to the microscopic, and how this has prompted changes in public policy to mitigate the disease's impact. I also examine the latest trend of viewing pandemic influenza as a security threat and how this has changed contemporary governance structures and power dynamics.",,"Kamradt-Scott, Adam",,,,
,PMC,Therapeutic Value of Small Molecule Inhibitor to Plasminogen Activator Inhibitor–1 for Lung Fibrosis,http://dx.doi.org/10.1165/rcmb.2011-0139OC,PMC3262658,,,"Fibrosis is a final stage of many lung diseases, with no effective treatment. Plasminogen activator inhibitor–1 (PAI-1), a primary inhibitor of tissue-type and urokinase-type plasminogen activators (tPA and uPA, respectively), plays a critical role in the development of fibrosis. In this study, we explored the therapeutic potential of an orally effective small molecule PAI-1 inhibitor, TM5275, in a model of lung fibrosis induced by transforming growth factor–β1 (TGF-β1), the most potent and ubiquitous profibrogenic cytokine, and in human lung fibroblasts (CCL-210 cells). The results show that an intranasal instillation of AdTGF-β1(223/225), an adenovirus expressing constitutively active TGF-β1, increased the expression of PAI-1 and induced fibrosis in murine lung tissue. On the other hand, treating mice with 40 mg/kg of TM5275 for 10 days, starting 4 days after the instillation of AdTGF-β1(223/225), restored the activities of uPA and tPA and almost completely blocked TGF-β1–induced lung fibrosis, as shown by collagen staining, Western blotting, and the measurement of hydroxyproline. No loss of body weight was evident under these treatment conditions with TM5275. Furthermore, we show that TM5275 induced apoptosis in both myofibroblasts (TGF-β1–treated) and naive (TGF-β1–untreated) human lung fibroblasts, and this apoptosis was associated with the activation of caspase-3/7, the induction of p53, and the inhibition of α–smooth muscle actin, fibronectin, and PAI-1 expression. Such an inhibition of fibrotic responses by TM5275 occurred even in cells pretreated with TGF-β1 for 6 hours. Together, the results suggest that TM5275 is a relatively safe and potent antifibrotic agent, with therapeutic potential in fibrotic lung disease.",,"['Huang, Wen-Tan', 'Vayalil, Praveen K.', 'Miyata, Toshio', 'Hagood, James', 'Liu, Rui-Ming']",,,,
,PMC,Social and News Media Enable Estimation of Epidemiological Patterns Early in the 2010 Haitian Cholera Outbreak,http://dx.doi.org/10.4269/ajtmh.2012.11-0597,PMC3247107,,,"During infectious disease outbreaks, data collected through health institutions and official reporting structures may not be available for weeks, hindering early epidemiologic assessment. By contrast, data from informal media are typically available in near real-time and could provide earlier estimates of epidemic dynamics. We assessed correlation of volume of cholera-related HealthMap news media reports, Twitter postings, and government cholera cases reported in the first 100 days of the 2010 Haitian cholera outbreak. Trends in volume of informal sources significantly correlated in time with official case data and was available up to 2 weeks earlier. Estimates of the reproductive number ranged from 1.54 to 6.89 (informal sources) and 1.27 to 3.72 (official sources) during the initial outbreak growth period, and 1.04 to 1.51 (informal) and 1.06 to 1.73 (official) when Hurricane Tomas afflicted Haiti. Informal data can be used complementarily with official data in an outbreak setting to get timely estimates of disease dynamics.",,"['Chunara, Rumi', 'Andrews, Jason R.', 'Brownstein, John S.']",,,,
,PMC,Rapid Identification of Pseudallescheria and Scedosporium Strains by Using Rolling Circle Amplification,http://dx.doi.org/10.1128/AEM.05280-11,PMC3255646,,,"The Pseudallescheria boydii complex, comprising environmental pathogens with Scedosporium anamorphs, has recently been subdivided into five main species: Scedosporium dehoogii, S. aurantiacum, Pseudallescheria minutispora, P. apiosperma, and P. boydii, while the validity of some other taxa is being debated. Several Pseudallescheria and Scedosporium species are indicator organisms of pollution in soil and water. Scedosporium dehoogii in particular is enriched in soils contaminated by aliphatic hydrocarbons. In addition, the fungi may cause life-threatening infections involving the central nervous system in severely impaired patients. For screening purposes, rapid and economic tools for species recognition are needed. Our aim is to establish rolling circle amplification (RCA) as a screening tool for species-specific identification of Pseudallescheria and Scedosporium. With this aim, a set of padlock probes was designed on the basis of the internal transcribed spacer (ITS) region, differing by up to 13 fixed mutations. Padlock probes were unique as judged from sequence comparison by BLAST search in GenBank and in dedicated research databases at CBS (Centraalbureau voor Schimmelcultures Fungal Biodiversity Centre). RCA was applied as an in vitro tool, tested with pure DNA amplified from cultures. The species-specific padlock probes designed in this study yielded 100% specificity. The method presented here was found to be an attractive alternative to identification by restriction fragment length polymorphism (RFLP) or sequencing. The rapidity (<1 day), specificity, and low costs make RCA a promising screening tool for environmentally and clinically relevant fungi.",,"['Lackner, Michaela', 'Najafzadeh, Mohammad Javad', 'Sun, Jiufeng', 'Lu, Qiaoyun', 'de Hoog, G. Sybren']",,,,
,PMC,Distinct immunoregulatory cytokine pattern in Egyptian patients with occult Hepatitis C infection and unexplained persistently elevated liver transaminases,http://dx.doi.org/10.4103/0973-6247.95046,PMC3353624,22623838,CC BY-NC-SA,"BACKGROUND/AIM: The immunopathogenesis of occult Hepatitis C virus (HCV) infection is a matter of great controversy and has been suggested to involve a complex balance between cytokines with pro- and anti-inflammatory activity. This work aimed at studying the serum Th1 and Th2 cytokine production in patients with occult HCV infection. MATERIALS AND METHODS: Serum levels of cytokines of Th1 (interleukin [IL]-2, INF-γ) and Th2 (IL-4) were measured in 27 patients with occult HCV infection and 28 patients with chronic hepatitis C infection. RESULTS: The levels of IL-2 and interferon-γ were highly significantly increased in patients with chronic HCV infection (P<0.001). IL-4 was highly significantly increased in occult HCV infection (P<0.001). Significant increases were noted in chronic HCV infection regarding bilirubin (P<0.001), ALT (P = 0.009), AST (P = 0.013), AFP (P<0.001), while serum albumin was significantly higher in occult HCV infection (P<0.001). Necroinflammation (P<0.001), fibrosis (P<0.001), and cirrhosis (P = 0.03) were significantly increased in chronic HCV infection. CONCLUSION: Our data revealed a high prevalence of occult HCV infection (25%) in patients with unexplained persistently abnormal liver function test results. Those patients exhibited a distinct immunoregulatory cytokine pattern, favoring viral persistence and explaining the less aggressive course of this disease entity than chronic HCV infection.",2012 Jan-Jun,"['Gad, Yahia Z.', 'Mouas, Narres', 'Abdel-Aziz, Azza', 'Abousmra, Nashwa', 'Elhadidy, Mona']",Asian J Transfus Sci,,,
,PMC,Mapping the New World of Necrotizing Enterocolitis (NEC): Review and Opinion,,PMC3666872,,,"A comprehensive review of necrotizing enterocolitis (NEC) is provided; including history, biological basis and frequently asked questions. In addition, a system of improved NEC classification is explained in detail (consisting of five NEC subsets and four NEC-like diseases), to aid the bedside clinician in therapy and prevention. The authors offer opinion for therapeutics in italics at the end of each definition.",,"['Gordon, Phillip', 'Christensen, Robert', 'Weitkamp, Jörn-Hendrik', 'Maheshwari, Akhil']",,,,
,PMC,Ferret Thoracic Anatomy by 2-Deoxy-2-(18F)Fluoro-D-Glucose (18F-FDG) Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) Imaging,http://dx.doi.org/10.1093/ilar.53.1.9,PMC3573861,,,"The domestic ferret (Mustela putorius furo) has been a long-standing animal model used in the evaluation and treatment of human diseases. Molecular imaging techniques such as 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) positron emission tomography (PET) would be an invaluable method of tracking disease in vivo, but this technique has not been reported in the literature. Thus, the aim of this study was to establish baseline imaging characteristics of PET/computed tomography (CT) with (18)F-FDG in the ferret model. Twelve healthy female ferrets were anesthetized and underwent combined PET/CT scanning. After the images were fused, volumes of interest (VOIs) were generated in the liver, heart, thymus, and bilateral lung fields. For each VOI, standardized uptake values (SUVs) were calculated. Additional comparisons were made between radiotracer uptake periods (60, 90, and >90 minutes), intravenous and intraperitoneal injections of (18)F-FDG, and respiratory gated and ungated acquisitions. Pulmonary structures and the surrounding thoracic and upper abdominal anatomy were readily identified on the CT scans of all ferrets and were successfully fused with PET. VOIs were created in various tissues with the following SUV calculations: heart (maximum standardized uptake value [SUV(Max)] 8.60, mean standardized uptake value [SUV(Mean)] 5.42), thymus (SUV(Max) 3.86, SUV(Mean) 2.59), liver (SUV(Max) 1.37, SUV(Mean) 0.99), right lung (SUV(Max) 0.92, SUV(Mean) 0.56), and left lung (SUV(Max) 0.88, SUV(Mean) 0.51). Sixty- to 90-minute uptake periods were sufficient to separate tissues based on background SUV activity. No gross differences in image quality were seen between intraperitoneal and intravenous injections of (18)F-FDG. Respiratory gating also did not have a significant impact on image quality of lung parenchyma. The authors concluded that (18)F-FDG PET and CT imaging can be performed successfully in normal healthy ferrets with the parameters identified in this study. They obtained similar imaging features and uptake measurements with and without respiratory gating as well as with intraperitoneal and intravenous (18)F-FDG injections. (18)F-FDG PET and CT can be a valuable resource for the in vivo tracking of disease progression in future studies that employ the ferret model.",,"['Wu, Albert', 'Zheng, Huaiyu', 'Kraenzle, Jennifer', 'Biller, Ashley', 'Vanover, Carol D.', 'Proctor, Mary', 'Sherwood, Leslie', 'Steffen, Marlene', 'Ng, Chin', 'Mollura, Daniel J.', 'Jonsson, Colleen B.']",,,,
,PMC,Molecular mimicry as an inducing trigger for CNS autoimmune demyelinating disease,http://dx.doi.org/10.1111/j.1600-065X.2011.01076.x,PMC3586283,,,"Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that affects about 0.1% of the worldwide population. This deleterious disease is marked by infiltration of myelinspecific T cells that attack the protective myelin sheath that surrounds CNS nerve axons. Upon demyelination, saltatory nerve conduction is disrupted, and patients experience neurologic deficiencies. The exact cause for MS remains unknown, although most evidence supports the hypothesis that both genetic and environmental factors contribute to disease development. Epidemiologic evidence supports a role for environmental pathogens, such as viruses, as potentially key contributors to MS induction. Pathogens can induce autoimmunity via several well-studied mechanisms with the most postulated being molecular mimicry. Molecular mimicry occurs when T cells specific for peptide epitopes derived from pathogens cross-react with self-epitopes, leading to autoimmune tissue destruction. In this review, we discuss an in vivo virus-induced mouse model of MS developed in our laboratory, which has contributed greatly to our understanding of the mechanisms underlying molecular mimicry-induced CNS autoimmunity.",,"['Chastain, Emily M. L.', 'Miller, Stephen D.']",,,,
,PMC,The Time of the Insult/Triggering Event in Legg-Calvé-Perthes' Disease Determined by Incubation Period Modeling and the Age Distribution of Children with Perthes',,PMC3565417,,,"The time when the insult/triggering event occurs in Legg-Calvé-Perthes' (LCPD) is unknown. the purpose of this study was to determine, using the mathematical tool of incubation period modeling, the time of such event and the incubation period for LCPD. We reviewed 2,911 children with LCPD from 10 different centers around the world. They were divided into two groups: those from India (505 children, mean age 8.1 ± 2.3 years) and those from other than India (2,406 children, mean age 5.8 ± 2.2 years). A simple distribution with an excellent fit to the data was ln(y) = a + bx + cxln(x), where y is the proportion of children with LCPD at age of diagnosis x (r(2) = 0.994 for non-Indian and 0.959 for Indian children). The age of the triggering event was 1.32 years for non-Indian and 2.77 years for Indian children; the median incubation period was 4.30 years non-Indian and 5.33 years for Indian patients. Knowing the incubation period and age of triggering event narrows the number of potential etiologies in LCPD. this study does not support a prenatal triggering event as postulated in the past. similar incubation periods with different ages at diagnosis supports a common insult which occurs at different ages in different populations dependent upon local factors such as geographic location and ethnicity.",,"['Loder, Randall T.', 'Browne, Richard H.', 'Millis, Andrew', 'Kim, Wook-Cheol', 'Shah, Hitesh', 'Cosgrove, Aidan P.', 'Wiig, Ola']",,,,
,PMC,Suprapubic Bladder Catheterization of Male Spinal-Cord–Injured Sprague–Dawley Rats,,PMC3276970,,,"The rat spinal-cord–injury (SCI) model is widely used to study the pathologic mechanisms that contribute to sensory and motor dysfunction in humans. This model is thought to mimic many of the negative outcomes experienced by humans after spinal contusion injury. We theorized that manual bladder expression contributed to the kidney and bladder lesions reported in previous studies using the rat SCI model. In the present study, rats were surgically implanted with bladder catheters after spinal contusion injury to provide continuous drainage of urine. After 72 h, the rats were euthanized and their kidneys and bladders examined histologically. BUN, serum creatinine, and urine protein were compared at 0 and 72 h after surgery. Kidney and bladder lesions were similar in SCI rats with and without implanted bladder catheters. BUN at 72 h was higher than baseline values in both groups, whereas serum creatinine was higher at 72 h compared with baseline values only in the catheterized rats. These findings indicate that suprapubic bladder catheterization does not reduce hydronephrosis in SCI rats and that the standard of care for bladder evacuation should continue to be manual expression of urine.",,"['Robinson, Mary A', 'Herron, Alan J', 'Goodwin, Bradford S', 'Grill, Raymond J']",,,,
,PMC,Yield of Sputum for Viral Detection by Reverse Transcriptase PCR in Adults Hospitalized with Respiratory Illness,http://dx.doi.org/10.1128/JCM.05841-11,PMC3256730,,,"Diagnostic tests for respiratory viral infections have traditionally been performed on nasopharyngeal swabs or washings. Reverse transcriptase PCR (RT-PCR) is rapid, sensitive, and specific for viral infection diagnosis but is rarely applied to sputum samples. Thus, we evaluated the diagnostic yield of RT-PCR for detection of nine virus types by the use of nose and throat swabs (NTS) and sputum samples from patients admitted to the hospital with acute respiratory tract illnesses. Adults hospitalized with acute respiratory tract illnesses were recruited during the winters of 2008 and 2009. At enrollment, combined nose and throat swabs and sputum samples were collected for RT-PCR for detection of nine common respiratory virus types. A total of 532 subjects admitted for 556 respiratory illnesses were enrolled. A total of 189 virus strains were identified. The diagnostic yields for detection of any virus were 23% (126/556) for NTS RT-PCR and 36% (146/404) for sputum RT-PCR. A total of 83 (44%) of 189 viral detections were positive by both methods, 43 (23%) were positive by NTS alone, and 63 (33%) were positive only with sputum samples. The inclusion of RT-PCR performed with sputum samples significantly increased the diagnostic yield for respiratory viral infections in adults. Further studies designed to adapt the use of sputum samples for commercial RT-PCR respiratory virus assays are needed.",,"['Falsey, Ann R.', 'Formica, Maria A.', 'Walsh, Edward E.']",,,,
,PMC,Review of Medical Image Classification using the Adaptive Neuro-Fuzzy Inference System,,PMC3592505,23493054,CC BY-NC-SA,"Image classification is an issue that utilizes image processing, pattern recognition and classification methods. Automatic medical image classification is a progressive area in image classification, and it is expected to be more developed in the future. Because of this fact, automatic diagnosis can assist pathologists by providing second opinions and reducing their workload. This paper reviews the application of the adaptive neuro-fuzzy inference system (ANFIS) as a classifier in medical image classification during the past 16 years. ANFIS is a fuzzy inference system (FIS) implemented in the framework of an adaptive fuzzy neural network. It combines the explicit knowledge representation of an FIS with the learning power of artificial neural networks. The objective of ANFIS is to integrate the best features of fuzzy systems and neural networks. A brief comparison with other classifiers, main advantages and drawbacks of this classifier are investigated.",2012 Jan-Apr,"['Hosseini, Monireh Sheikh', 'Zekri, Maryam']",J Med Signals Sens,,,
,PMC,Antiviral Decoction of Isatidis Radix (板藍根 bǎn lán gēn) Inhibited Influenza Virus Adsorption on MDCK Cells by Cytoprotective Activity,,PMC3943010,24716114,CC BY-NC-SA,"The aim of this study is to elucidate how the Isatidis Radix (板藍根 bǎn lán gēn) tonic, as an aqueous mixture of hundreds of compositions, interrupts the infection of influenza viruses to their host cells. The efficacy of the tonic was evaluated and expressed as cell proliferation rate and plaque reduction rate in Madin-Darby Canine Kidney (MDCK) cells, against 3 strains of influenza A and B viruses. This boiling water (at 100°C) extract of Isatidis Radix (RIE) showed antiviral activity against influenza virus A and B. The concentration for 50% inhibition of influenza virus A replication (IC(50)) in MDCK cell was 12.6 mg/mL with a therapeutic index >8. When cells were incubated with RIE prior to virus adsorption, the numbers of viable cell were at least doubled compared to the numbers of virus control, RIE incubation after virus adsorption and RIE incubation with virus prior to adsorption, in both influenza virus A and B. Moreover, much less virus particles were spotted by scanning electron microscope (SEM) in the RIE pre-treated cells than the cells without RIE treatment. These results indicate the antiviral activity of RIE is mainly attributed to its host cell protection effect but not actions on virus or post-virus-adsorption interruption. Cell, but not virus, is more likely to be the action target of RIE.",2012 Jan-Mar,"['Ke, Lijing', 'Wen, Teng', 'Bradshaw, Jeremy P', 'Zhou, Jianwu', 'Rao, Pingfan']",J Tradit Complement Med,,,
,PMC,Complex Dynamic Development of Poliovirus Membranous Replication Complexes,http://dx.doi.org/10.1128/JVI.05937-11,PMC3255921,,,"Replication of all positive-strand RNA viruses is intimately associated with membranes. Here we utilize electron tomography and other methods to investigate the remodeling of membranes in poliovirus-infected cells. We found that the viral replication structures previously described as “vesicles” are in fact convoluted, branching chambers with complex and dynamic morphology. They are likely to originate from cis-Golgi membranes and are represented during the early stages of infection by single-walled connecting and branching tubular compartments. These early viral organelles gradually transform into double-membrane structures by extension of membranous walls and/or collapsing of the luminal cavity of the single-membrane structures. As the double-membrane regions develop, they enclose cytoplasmic material. At this stage, a continuous membranous structure may have double- and single-walled membrane morphology at adjacent cross-sections. In the late stages of the replication cycle, the structures are represented mostly by double-membrane vesicles. Viral replication proteins, double-stranded RNA species, and actively replicating RNA are associated with both double- and single-membrane structures. However, the exponential phase of viral RNA synthesis occurs when single-membrane formations are predominant in the cell. It has been shown previously that replication complexes of some other positive-strand RNA viruses form on membrane invaginations, which result from negative membrane curvature. Our data show that the remodeling of cellular membranes in poliovirus-infected cells produces structures with positive curvature of membranes. Thus, it is likely that there is a fundamental divergence in the requirements for the supporting cellular membrane-shaping machinery among different groups of positive-strand RNA viruses.",,"['Belov, George A.', 'Nair, Vinod', 'Hansen, Bryan T.', 'Hoyt, Forrest H.', 'Fischer, Elizabeth R.', 'Ehrenfeld, Ellie']",,,,
,PMC,Macromolecular Assembly-Driven Processing of the 2/3 Cleavage Site in the Alphavirus Replicase Polyprotein,http://dx.doi.org/10.1128/JVI.05195-11,PMC3255916,,,"Semliki Forest virus (SFV) is a member of the Alphavirus genus, which produces its replicase proteins in the form of a nonstructural (ns) polyprotein precursor P1234. The maturation of the replicase occurs in a temporally controlled manner by protease activity of nsP2. The template preference and enzymatic capabilities of the alphaviral replication complex have a very important connection with its composition, which is irreversibly altered by proteolysis. The final cleavage of the 2/3 site in the ns polyprotein apparently leads to significant rearrangements within the replication complex and thus denotes the “point of no return” for viral replication progression. Numerous studies have devised rules for when and how ns protease acts, but how the alphaviral 2/3 site is recognized remained largely unexplained. In contrast to the other two cleavage sites within the ns polyprotein, the 2/3 site evidently lacks primary sequence elements in the vicinity of the scissile bond sufficient for specific protease recognition. In this study, we sought to investigate the molecular details of the regulation of the 2/3 site processing in the SFV ns polyprotein. We present evidence that correct macromolecular assembly, presumably strengthened by exosite interactions rather than the functionality of the individual nsP2 protease, is the driving force for specific substrate targeting. We conclude that structural elements within the macrodomain of nsP3 are used for precise positioning of a substrate recognition sequence at the catalytic center of the protease and that this process is coordinated by the exact N-terminal end of nsP2, thus representing a unique regulation mechanism used by alphaviruses.",,"['Lulla, Aleksei', 'Lulla, Valeria', 'Merits, Andres']",,,,
,PMC,Human Coronavirus-Induced Neuronal Programmed Cell Death Is Cyclophilin D Dependent and Potentially Caspase Dispensable,http://dx.doi.org/10.1128/JVI.06062-11,PMC3255912,,,"Human coronaviruses (HCoV) are recognized respiratory pathogens. Some HCoV strains, including HCoV-OC43, can invade the central nervous system, where they infect neurons, with unclear consequences. We have previously reported that HCoV-OC43 infection of human neurons activates the unfolded-protein response and caspase-3 and induces cell death and that the viral spike (S) glycoprotein is involved in the process. We now report on underlying mechanisms associated with the induction of programmed cell death (PCD) after infection by the reference HCoV-OC43 virus (rOC/ATCC) and a more neurovirulent and cytotoxic HCoV-OC43 variant harboring two point mutations in the S glycoprotein (rOC/U(S183-241)). Even though caspase-3 and caspase-9 were both activated after infection, the use of caspase inhibitors neither reduced nor delayed virus-induced PCD, suggesting that these proteases are not essential in the process. On the other hand, the proapoptotic proteins BAX, cytochrome c (CytC), and apoptosis-inducing factor (AIF) were relocalized toward the mitochondria, cytosol, and nucleus, respectively, after infection by both virus variants. Moreover, LA-N-5 neuronal cells treated with cyclosporine (CsA), an inhibitor of the mitochondrial permeabilization transition pore (mPTP), or knocked down for cyclophilin D (CypD) were completely protected from rOC/ATCC-induced neuronal PCD, underlining the involvement of CypD in the process. On the other hand, CsA and CypD knockdown had moderate effects on rOC/U(S183-241)-induced PCD. In conclusion, our results are consistent with mitochondrial AIF and cyclophilin D being central in HCoV-OC43-induced PCD, while caspases appear not to be essential.",,"['Favreau, Dominique J.', 'Meessen-Pinard, Mathieu', 'Desforges, Marc', 'Talbot, Pierre J.']",,,,
,PMC,Cathepsin Cleavage Potentiates the Ebola Virus Glycoprotein To Undergo a Subsequent Fusion-Relevant Conformational Change,http://dx.doi.org/10.1128/JVI.05708-11,PMC3255896,,,"Cellular entry of Ebola virus (EBOV), a deadly hemorrhagic fever virus, is mediated by the viral glycoprotein (GP). The receptor-binding subunit of GP must be cleaved (by endosomal cathepsins) in order for entry and infection to proceed. Cleavage appears to proceed through 50-kDa and 20-kDa intermediates, ultimately generating a key 19-kDa core. How 19-kDa GP is subsequently triggered to bind membranes and induce fusion remains a mystery. Here we show that 50-kDa GP cannot be triggered to bind to liposomes in response to elevated temperature but that 20-kDa and 19-kDa GP can. Importantly, 19-kDa GP can be triggered at temperatures ∼10°C lower than 20-kDa GP, suggesting that it is the most fusion ready form. Triggering by heat (or urea) occurs only at pH 5, not pH 7.5, and involves the fusion loop, as a fusion loop mutant is defective in liposome binding. We further show that mild reduction (preferentially at low pH) triggers 19-kDa GP to bind to liposomes, with the wild-type protein being triggered to a greater extent than the fusion loop mutant. Moreover, mild reduction inactivates pseudovirion infection, suggesting that reduction can also trigger 19-kDa GP on virus particles. Our results support the hypothesis that priming of EBOV GP, specifically to the 19-kDa core, potentiates GP to undergo subsequent fusion-relevant conformational changes. Our findings also indicate that low pH and an additional endosomal factor (possibly reduction or possibly a process mimicked by reduction) act as fusion triggers.",,"['Brecher, Matthew', 'Schornberg, Kathryn L.', 'Delos, Sue E.', 'Fusco, Marnie L.', 'Saphire, Erica Ollmann', 'White, Judith M.']",,,,
,PMC,Identification of a Novel Feline Picornavirus from the Domestic Cat,http://dx.doi.org/10.1128/JVI.06253-11,PMC3255865,,,"While picornaviruses are known to infect different animals, their existence in the domestic cat was unknown. We describe the discovery of a novel feline picornavirus (FePV) from stray cats in Hong Kong. From samples from 662 cats, FePV was detected in fecal samples from 14 cats and urine samples from 2 cats by reverse transcription-PCR (RT-PCR). Analysis of five FePV genomes revealed a distinct phylogenetic position and genomic features, with low sequence homologies to known picornaviruses especially in leader and 2A proteins. Among the viruses that belong to the closely related bat picornavirus groups 1 to 3 and the genus Sapelovirus, G+C content and sequence analysis of P1, P2, and P3 regions showed that FePV is most closely related to bat picornavirus group 3. However, FePV possessed other distinct features, including a putative type IV internal ribosome entry site/segment (IRES) instead of type I IRES in bat picornavirus group 3, protein cleavage sites, and H-D-C catalytic triad in 3C(pro) different from those in sapeloviruses and bat picornaviruses, and the shortest leader protein among known picornaviruses. These results suggest that FePV may belong to a new genus in the family Picornaviridae. Western blot analysis using recombinant FePV VP1 polypeptide showed a high seroprevalence of 33.6% for IgG among the plasma samples from 232 cats tested. IgM was also detected in three cats positive for FePV in fecal samples, supporting recent infection in these cats. Further studies are important to understand the pathogenicity, epidemiology, and genetic evolution of FePV in these common pet animals.",,"['Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Yip, Cyril C. Y.', 'Choi, Garnet K. Y.', 'Wu, Ying', 'Bai, Ru', 'Fan, Rachel Y. Y.', 'Lai, Kenneth K. Y.', 'Chan, Kwok-Hung', 'Yuen, Kwok-Yung']",,,,
,PMC,RNA Interference against Animal Viruses: How Morbilliviruses Generate Extended Diversity To Escape Small Interfering RNA Control,http://dx.doi.org/10.1128/JVI.06210-11,PMC3255857,,,"Viruses are serious threats to human and animal health. Vaccines can prevent viral diseases, but few antiviral treatments are available to control evolving infections. Among new antiviral therapies, RNA interference (RNAi) has been the focus of intensive research. However, along with the development of efficient RNAi-based therapeutics comes the risk of emergence of resistant viruses. In this study, we challenged the in vitro propensity of a morbillivirus (peste des petits ruminants virus), a stable RNA virus, to escape the inhibition conferred by single or multiple small interfering RNAs (siRNAs) against conserved regions of the N gene. Except with the combination of three different siRNAs, the virus systematically escaped RNAi after 3 to 20 consecutive passages. The genetic modifications involved consisted of single or multiple point nucleotide mutations and a deletion of a stretch of six nucleotides, illustrating that this virus has an unusual genomic malleability.",,"['Holz, Carine L.', 'Albina, Emmanuel', 'Minet, Cécile', 'Lancelot, Renaud', 'Kwiatek, Olivier', 'Libeau, Geneviève', 'Servan de Almeida, Renata']",,,,
,PMC,"Transmissible Gastroenteritis Coronavirus RNA-Dependent RNA Polymerase and Nonstructural Proteins 2, 3, and 8 Are Incorporated into Viral Particles",http://dx.doi.org/10.1128/JVI.06428-11,PMC3255853,,,"Coronavirus replication and transcription are processes mediated by a protein complex, with the RNA-dependent RNA polymerase (RdRp) as a main component. Proteomic analysis of highly purified transmissible gastroenteritis virus showed the RdRp to be a component of the viral particles. This finding was confirmed by Western blotting, immunofluorescence, and immunoelectron microscopy analyses. Interestingly, the replicase nonstructural proteins 2, 3, and 8 colocalized with the RdRp in the viral factories and were also incorporated into the virions.",,"['Nogales, Aitor', 'Márquez-Jurado, Silvia', 'Galán, Carmen', 'Enjuanes, Luis', 'Almazán, Fernando']",,,,
,PMC,Ex Vivo and In Vivo Inhibition of Human Rhinovirus Replication by a New Pseudosubstrate of Viral 2A Protease,http://dx.doi.org/10.1128/JVI.05263-11,PMC3255852,,,"Human rhinoviruses (HRVs) remain a significant public health problem as they are the major cause of both upper and lower respiratory tract infections. Unfortunately, to date no vaccine or antiviral against these pathogens is available. Here, using a high-throughput yeast two-hybrid screening, we identified a 6-amino-acid hit peptide, LVLQTM, which acted as a pseudosubstrate of the viral 2A cysteine protease (2A(pro)) and inhibited its activity. This peptide was chemically modified with a reactive electrophilic fluoromethylketone group to form a covalent linkage with the nucleophilic active-site thiol of the enzyme. Ex vivo and in vivo experiments showed that thus converted, LVLQTM was a strong inhibitor of HRV replication in both A549 cells and mice. To our knowledge, this is the first report validating a compound against HRV infection in a mouse model.",,"['Falah, Nisrine', 'Violot, Sébastien', 'Décimo, Didier', 'Berri, Fatma', 'Foucault-Grunenwald, Marie-Laure', 'Ohlmann, Théophile', 'Schuffenecker, Isabelle', 'Morfin, Florence', 'Lina, Bruno', 'Riteau, Béatrice', 'Cortay, Jean-Claude']",,,,
,PMC,Molecular Determinants of Severe Acute Respiratory Syndrome Coronavirus Pathogenesis and Virulence in Young and Aged Mouse Models of Human Disease,http://dx.doi.org/10.1128/JVI.05957-11,PMC3255850,,,"SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease.",,"['Frieman, Matthew', 'Yount, Boyd', 'Agnihothram, Sudhakar', 'Page, Carly', 'Donaldson, Eric', 'Roberts, Anjeanette', 'Vogel, Leatrice', 'Woodruff, Becky', 'Scorpio, Diana', 'Subbarao, Kanta', 'Baric, Ralph S.']",,,,
,PMC,Impact of Host Proteases on Reovirus Infection in the Respiratory Tract,http://dx.doi.org/10.1128/JVI.06429-11,PMC3255841,,,"Virion uncoating is an essential early event in reovirus infection. In natural enteric infections, rapid proteolytic uncoating of virions is mediated by pancreatic serine proteases. The proteases that promote reovirus disassembly and cell entry in the respiratory tract remain unknown. In this report, we show that endogenous respiratory and inflammatory proteases can promote reovirus infection in vitro and that preexisting inflammation augments in vivo infection in the murine respiratory tract.",,"['Nygaard, Rachel M.', 'Golden, Joseph W.', 'Schiff, Leslie A.']",,,,
,PMC,Human Pulmonary Microvascular Endothelial Cells Support Productive Replication of Highly Pathogenic Avian Influenza Viruses: Possible Involvement in the Pathogenesis of Human H5N1 Virus Infection,http://dx.doi.org/10.1128/JVI.06348-11,PMC3255832,,,"Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to cause sporadic human infections with a high fatality rate. Respiratory failure due to acute respiratory distress syndrome (ARDS) is a complication among hospitalized patients. Since progressive pulmonary endothelial damage is the hallmark of ARDS, we investigated host responses following HPAI virus infection of human pulmonary microvascular endothelial cells. Evaluation of these cells for the presence of receptors preferred by influenza virus demonstrated that avian-like (α2-3-linked) receptors were more abundant than human-like (α2-6-linked) receptors. To test the permissiveness of pulmonary endothelial cells to virus infection, we compared the replication of selected seasonal, pandemic (2009 H1N1 and 1918), and potentially pandemic (H5N1) influenza virus strains. We observed that these cells support productive replication only of HPAI H5N1 viruses, which preferentially enter through and are released from the apical surface of polarized human endothelial monolayers. Furthermore, A/Thailand/16/2004 and A/Vietnam/1203/2004 (VN/1203) H5N1 viruses, which exhibit heightened virulence in mammalian models, replicated to higher titers than less virulent H5N1 strains. VN/1203 infection caused a significant decrease in endothelial cell proliferation compared to other subtype viruses. VN/1203 virus was also found to be a potent inducer of cytokines and adhesion molecules known to regulate inflammation during acute lung injury. Deletion of the H5 hemagglutinin (HA) multibasic cleavage site did not affect virus infectivity but resulted in decreased virus replication in endothelial cells. Our results highlight remarkable tropism and infectivity of the H5N1 viruses for human pulmonary endothelial cells, resulting in the potent induction of host inflammatory responses.",,"['Zeng, Hui', 'Pappas, Claudia', 'Belser, Jessica A.', 'Houser, Katherine V.', 'Zhong, Weiming', 'Wadford, Debra A.', 'Stevens, Troy', 'Balczon, Ron', 'Katz, Jacqueline M.', 'Tumpey, Terrence M.']",,,,
,PMC,Bromovirus RNA Replication Compartment Formation Requires Concerted Action of 1a's Self-Interacting RNA Capping and Helicase Domains,http://dx.doi.org/10.1128/JVI.05684-11,PMC3255829,,,"All positive-strand RNA viruses replicate their genomes in association with rearranged intracellular membranes such as single- or double-membrane vesicles. Brome mosaic virus (BMV) RNA synthesis occurs in vesicular endoplasmic reticulum (ER) membrane invaginations, each induced by many copies of viral replication protein 1a, which has N-terminal RNA capping and C-terminal helicase domains. Although the capping domain is responsible for 1a membrane association and ER targeting, neither this domain nor the helicase domain was sufficient to induce replication vesicle formation. Moreover, despite their potential for mutual interaction, the capping and helicase domains showed no complementation when coexpressed in trans. Cross-linking showed that the capping and helicase domains each form trimers and larger multimers in vivo, and the capping domain formed extended, stacked, hexagonal lattices in vivo. Furthermore, coexpressing the capping domain blocked the ability of full-length 1a to form replication vesicles and replicate RNA and recruited full-length 1a into mixed hexagonal lattices with the capping domain. Thus, BMV replication vesicle formation and RNA replication depend on the direct linkage and concerted action of 1a's self-interacting capping and helicase domains. In particular, the capping domain's strong dominant-negative effects showed that the ability of full-length 1a to form replication vesicles was highly sensitive to disruption by non-productively titrating lattice-forming self-interactions of the capping domain. These and other findings shed light on the roles and interactions of 1a domains in replication compartment formation and support prior results suggesting that 1a induces replication vesicles by forming a capsid-like interior shell.",,"['Diaz, Arturo', 'Gallei, Andreas', 'Ahlquist, Paul']",,,,
,PMC,Genetic Inactivation of COPI Coatomer Separately Inhibits Vesicular Stomatitis Virus Entry and Gene Expression,http://dx.doi.org/10.1128/JVI.05810-11,PMC3255828,,,"Viruses coopt cellular membrane transport to invade cells, establish intracellular sites of replication, and release progeny virions. Recent genome-wide RNA interference (RNAi) screens revealed that genetically divergent viruses require biosynthetic membrane transport by the COPI coatomer complex for efficient replication. Here we found that disrupting COPI function by RNAi inhibited an early stage of vesicular stomatitis virus (VSV) replication. To dissect which replication stage(s) was affected by coatomer inactivation, we used visual and biochemical assays to independently measure the efficiency of viral entry and gene expression in hamster (ldlF) cells depleted of the temperature-sensitive ε-COP subunit. We show that ε-COP depletion for 12 h caused a primary block to virus internalization and a secondary defect in viral gene expression. Using brefeldin A (BFA), a chemical inhibitor of COPI function, we demonstrate that short-term (1-h) BFA treatments inhibit VSV gene expression, while only long-term (12-h) treatments block virus entry. We conclude that prolonged coatomer inactivation perturbs cellular endocytic transport and thereby indirectly impairs VSV entry. Our results offer an explanation of why COPI coatomer is frequently identified in screens for cellular factors that support cell invasion by microbial pathogens.",,"['Cureton, David K.', 'Burdeinick-Kerr, Rebeca', 'Whelan, Sean P. J.']",,,,
,PMC,Arterivirus and Nairovirus Ovarian Tumor Domain-Containing Deubiquitinases Target Activated RIG-I To Control Innate Immune Signaling,http://dx.doi.org/10.1128/JVI.06277-11,PMC3255818,,,"The innate immune response constitutes the first line of defense against viral infection and is extensively regulated through ubiquitination. The removal of ubiquitin from innate immunity signaling factors by deubiquitinating enzymes (DUBs) therefore provides a potential opportunity for viruses to evade this host defense system. It was previously found that specific proteases encoded by the unrelated arteri- and nairoviruses resemble the ovarian tumor domain-containing (OTU) family of DUBs. In arteriviruses, this domain has been characterized before as a papain-like protease (PLP2) that is also involved in replicase polyprotein processing. In nairoviruses, the DUB resides in the polymerase protein but is not essential for RNA replication. Using both in vitro and cell-based assays, we now show that PLP2 DUB activity is conserved in all members of the arterivirus family and that both arteri- and nairovirus DUBs inhibit RIG-I-mediated innate immune signaling when overexpressed. The potential relevance of RIG-I-like receptor (RLR) signaling for the innate immune response against arterivirus infection is supported by our finding that in mouse embryonic fibroblasts, the production of beta interferon primarily depends on the recognition of arterivirus RNA by the pattern-recognition receptor MDA5. Interestingly, we also found that both arteri- and nairovirus DUBs inhibit RIG-I ubiquitination upon overexpression, suggesting that both MDA5 and RIG-I have a role in countering infection by arteriviruses. Taken together, our results support the hypothesis that arteri- and nairoviruses employ their deubiquitinating potential to inactivate cellular proteins involved in RLR-mediated innate immune signaling, as exemplified by the deubiquitination of RIG-I.",,"['van Kasteren, Puck B.', 'Beugeling, Corrine', 'Ninaber, Dennis K.', 'Frias-Staheli, Natalia', 'van Boheemen, Sander', 'García-Sastre, Adolfo', 'Snijder, Eric J.', 'Kikkert, Marjolein']",,,,
,PMC,Human Pathogens and the Host Cell SUMOylation System,http://dx.doi.org/10.1128/JVI.06227-11,PMC3255802,,,"Since posttranslational modification (PTM) by the small ubiquitin-related modifiers (SUMOs) was discovered over a decade ago, a huge number of cellular proteins have been found to be reversibly modified, resulting in alteration of differential cellular pathways. Although the molecular consequences of SUMO attachment are difficult to predict, the underlying principle of SUMOylation is altering inter- and/or intramolecular interactions of the modified substrate, changing localization, stability, and/or activity. Unsurprisingly, many different pathogens have evolved to exploit the cellular SUMO modification system due to its functional flexibility and far-reaching functional downstream consequences. Although the extensive knowledge gained so far is impressive, a definitive conclusion about the role of SUMO modification during virus infection in general remains elusive and is still restricted to a few, yet promising concepts. Based on the available data, this review aims, first, to provide a detailed overview of the current state of knowledge and, second, to evaluate the currently known common principles/molecular mechanisms of how human pathogenic microbes, especially viruses and their regulatory proteins, exploit the host cell SUMO modification system.",,"['Wimmer, Peter', 'Schreiner, Sabrina', 'Dobner, Thomas']",,,,
,PMC,A sensitive real-time PCR for detection and subgrouping of human respiratory syncytial virus,http://dx.doi.org/10.1016/j.jviromet.2011.11.012,PMC3405522,22119628,CC BY,"Improved diagnostic tools for rapid detection, quantitation, and subgrouping of human respiratory syncytial virus (RSV) are needed to aid the development and evaluation of novel intervention strategies. A quantitative real-time RT-PCR using specific locked nucleic acid (LNA) probes was developed to identify RSV and to distinguish RSV subgroups A and B (RSV LNA assay). RSV subgroup diversity and the relationship between viral load and disease severity in confirmed RSV infections were also explored. 264 archived respiratory specimens from pediatric patients were tested in parallel using the commercial multiplex Seeplex™ RV detection kit (Seegene) and the novel RSV LNA assay. The LNA assay demonstrated a significantly higher sensitivity than Seeplex, improving overall detection rates from 24% (64/264) to 32% (84/264). Detection limits of 9.0 × 10(1) and 6.0 × 10(2) copies/mL were observed for RSV A and B, respectively. RSV A was detected in 53/84 (63%) cases, and 31/84 (37%) were positive for RSV B. This novel method offers a rapid, quantitative, highly specific and sensitive approach to laboratory diagnosis of RSV.",2012 Jan,"['Do, Lien Anh Ha', 'van Doorn, H. Rogier', 'Bryant, Juliet E.', 'Nghiem, My Ngoc', 'Nguyen Van, Vinh Chau', 'Vo, Cong Khanh', 'Nguyen, Minh Dung', 'Tran, Tinh Hien', 'Farrar, Jeremy', 'de Jong, Menno D.']",J Virol Methods,,,
,PMC,Determination of host RNA helicases activity in viral replication,http://dx.doi.org/10.1016/B978-0-12-396546-2.00019-X,PMC4862593,,,"RNA helicases are encoded by all eukaryotic and prokaryotic cells and a minority of viruses. Activity of RNA helicases is necessary for all steps in the expression of cells and viruses and the host innate response to virus infection. Their vast functional repertoire is attributable to the core ATPase-dependent helicase domain in conjunction with flanking domains that are interchangeable and engage viral and cellular cofactors. Here, we address the important issue of host RNA helicases that are necessary for replication of a virus. The chapter covers approaches to identification and characterization of candidate helicases and methods to define the biochemical and biophysical parameters of specificity and functional activity of the enzymes. We discuss the context of cellular RNA helicase activity and virion-associated RNA helicases. The methodology and choice of controls fosters the assessment of the virologic scope of RNA helicases across divergent cell lineages and viral replication cycles.",,"['Sharma, Amit', 'Boris-Lawrie, Kathleen']",,,,
,PMC,Molecular Mechanics of RNA Translocases,http://dx.doi.org/10.1016/B978-0-12-396546-2.00006-1,PMC4407658,,,"Historically, research on RNA helicase and translocation enzymes has seemed like a footnote to the extraordinary progress in studies on DNA-remodeling enzymes. However, during the past decade, the rising wave of activity in RNA science has engendered intense interest in the behaviors of specialized motor enzymes that remodel RNA molecules. Functional, mechanistic, and structural investigations of these RNA enzymes have begun to reveal the molecular basis for their key roles in RNA metabolism and signaling. In this chapter, we highlight the structural and mechanistic similarities among monomeric RNA translo-case enzymes, while emphasizing the many divergent characteristics that have caused this enzyme family to become one of the most important in metabolism and gene expression.",,"['Ding, Steve C.', 'Pyle, Anna Marie']",,,,
,PMC,Carbohydrate Antigen Microarrays,http://dx.doi.org/10.1007/978-1-61779-373-8_17,PMC6209592,,,"This chapter describes one of my laboratory’s working protocols for carbohydrate-based microarrays. Using a standard microarray spotter, we print carbohydrate antigens directly on the nitrocellulose-coated bioarray substrates. Because these substrates support noncovalent immobilization of many spotted antigens, in general no chemical modification of the antigen is needed for microarray production. Thus, this bioarray platform is technically simple and applicable for high-throughput construction of carbohydrate antigen microarrays. A number of nitrocellulose-coated glass slides with different technical characteristics are commercially available. Given the structural diversity of carbohydrate antigens, examining each antigen preparation to determine the efficacy of its immobilization in a given type of substrate and the surface display of the desired glycoepitopes in a microarray assay is essential.",,"Wang, Denong",,,,
,PMC,The ISG15 Conjugation System,http://dx.doi.org/10.1007/978-1-61779-474-2_9,PMC5912894,,,"ISG15 is a ubiquitin-like modifier that is expressed in response to type 1 interferon signaling (IFN-α/β) and plays a role in antiviral responses. The core E1, E2, and E3 enzymes for ISG15 are Ube1L, UbcH8, and Herc5, respectively, and these are all also induced at the transcriptional level by IFN-α/β. We recently showed that Herc5 associates with polysomes and modifies target proteins in a cotranslational manner. Here, we describe the expression of the core conjugating enzymes in human cells, the detection of ISG15 conjugates, and the methods for fractionation of Herc5 with polysomes.",,"['Durfee, Larissa A.', 'Huibregtse, Jon M.']",,,,
,PMC,Outcomes and Duration of Pneumocystis jirovecii Pneumonia Therapy in Infants with Severe Combined Immunodeficiency,http://dx.doi.org/10.1097/INF.0b013e31822db772,PMC3244569,,,"This retrospective review of patients with severe combined immunodeficiency and Pneumocystis jirovecii pneumonia (PCP) evaluated the relationship between duration of therapy to treat PCP and overall survival. We found that 80% of patients receiving only 21 days of antibiotics survived to 12 months beyond hematopoetic cell transplant, whereas only 25% of patients who required longer treatment for PCP survived to stem cell engraftment.",,"['Lundgren, Ingrid S.', 'Englund, Janet A.', 'Burroughs, Lauri M.', 'Torgerson, Troy R.', 'Skoda-Smith, Suzanne']",,,,
,PMC,Lessons Learned from an ICD-10-CM Clinical Documentation Pilot Study,,PMC3329200,,,"On October 1, 2013, the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) will be mandated for use in the United States in place of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). This new classification system will used throughout the nation's healthcare system for recording diagnoses or the reasons for treatment or care. A pilot study was conducted to determine whether current levels of inpatient clinical documentation provide the detail necessary to fully utilize the ICD-10-CM classification system for heart disease, pneumonia, and diabetes cases. The design of this pilot study was cross-sectional. Four hundred ninety-one de-identified records from two sources were coded using ICD-10-CM guidelines and codebooks. The findings of this study indicate that healthcare organizations need to assess clinical documentation and identify gaps. In addition, coder proficiency should be assessed prior to ICD-10-CM implementation to determine the need for further education and training in the biomedical sciences, along with training in the new classification system.",,"['Moczygemba, Jackie', 'Fenton, Susan H']",,,,
,PMC,Association of genetic variants in the IRAK-4 gene with susceptibility to severe sepsis,http://dx.doi.org/10.5847/wjem.j.issn.1920-8642.2012.02.008,PMC4129800,,,"BACKGROUND: The association of genetic variation in the IRAK-1 gene with sepsis outcome has been proved. However, few studies have addressed the impact of the IRAK-4 gene variants on sepsis risk. This study aimed to determine whether the polymorphisms in the IRAK-4 gene are associated with susceptibility to and prognosis of severe sepsis in the Chinese Han ethnic population. METHODS: In this case-control study, 192 patients with severe sepsis hospitalized in the emergency department of Zhongshan Hospital from February 2006 to December 2009 and 192 healthy volunteers were enrolled. Exclusion criteria included metastatic tumors, autoimmune diseases, AIDS or treatment with immunosuppressive drugs. This study was approved by the ethical committee of Zhongshan Hospital, Fudan University. Sepsis patients were divided into a survival group (n=124) and a non-survival group (n=68) according to the 30-day mortality. Primer 3 software was used to design PCR and sequencing primers. Genomic DNA was extracted from peripheral blood mononuclear cells. Seven tagSNPs in IRAK-4 were selected according to the data of the Chinese Han population in Beijing from the Hapmap project and genotyped by direct sequencing. The chi-square test was used to evaluate the differences in genotype and allele frequencies between the two groups. RESULTS: The distributions of all tagSNPs were consistent with Hardy-Weinberg equilibrium. The allele and genotype frequencies of rs4251545 (G/A) were significantly different between the severe sepsis and healthy control groups (P=0.015, P=0.035, respectively). Carriers of the rs4251545A had a higher risk for severe sepsis compared with carriers of the rs4251545G (OR=1.69, 95% CI: 1.10-2.58). The allele and genotype frequencies of all SNPs were not significantly different between the survival group and non-survival group. CONCLUSION: These findings indicate that the variants in IRAK-4 are significantly associated with susceptibility to severe sepsis in the Chinese Han ethnic population.",,"['Yin, Jun', 'Yao, Chen-ling', 'Liu, Cheng-long', 'Song, Zhen-ju', 'Tong, Chao-yang', 'Huang, Pei-zhi']",,,,
,PMC,Mathematical Modeling of Viral Zoonoses in Wildlife,http://dx.doi.org/10.1111/j.1939-7445.2011.00104.x,PMC3358807,,,"Zoonoses are a worldwide public health concern, accounting for approximately 75% of human infectious diseases. In addition, zoonoses adversely affect agricultural production and wildlife. We review some mathematical models developed for the study of viral zoonoses in wildlife and identify areas where further modeling efforts are needed.",,"['Allen, L. J. S.', 'Brown, V. L.', 'Jonsson, C. B.', 'Klein, S. L.', 'Laverty, S. M.', 'Magwedere, K.', 'Owen, J. C.', 'van den Driessche, P.']",,,,
,PMC,"Effectiveness of Non-pharmaceutical Interventions in Controlling an Influenza A Outbreak in a School, Thailand, November 2007",,PMC3597122,,,"Non-pharmaceutical interventions are often recommended as a component of integrated control measures for pandemic influenza, but the effectiveness needs to be evaluated. An outbreak of influenza A (H1N1) in northern Thailand in November 2007 offered opportunity to evaluate these interventions. An investigation was conducted to describe the outbreak, evaluate effectiveness of non-pharmaceutical interventions and assess surge capacity of health agencies. A descriptive study was conducted by interviewing students and personnel in a school. We characterized transmission of the virus in this outbreak and explored effects of control measures. We identified that 44% of the students and teachers developed influenza during the 19-day outbreak. Non-pharmaceutical interventions including school closure, setting up a field hospital and community health education were implemented. These measures possibly limited the outbreak spreading to other schools nearby. Surveillance and preparedness plans could be strengthened to respond to pandemic and inter-pandemic influenza by using non-pharmaceutical interventions.",,"['Sonthichai, Chaninan', 'Iamsirithaworn, S', 'Cummings, DAT', 'Shokekird, P', 'Niramitsantipong, A', 'Khumket, S', 'Chittaganpitch, M', 'Lessler, J']",,,,
,PMC,Human tRNA(Lys3)(UUU) is Pre-Structured by Natural Modifications for Cognate and Wobble Codon Binding through Keto-EnolTautomerism,http://dx.doi.org/10.1016/j.jmb.2011.12.048,PMC3662832,,,"Human tRNA(Lys3)(UUU) (htRNA(Lys3)(UUU)) decodes the lysine codons AAA and AAG during translation, and also plays a crucial role as the primer for HIV-1 reverse transcription. The post-transcriptional modifications 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U(34)), 2-methylthio-N(6)-threonylcarbamoyladenosine (ms(2)t(6)A(37))and pseudouridine (ψ(39)) in the tRNA'santicodon loop are critical for ribosomal binding and HIV-1 reverse transcription. To understand the importance of modified nucleoside contributions, the structure and function of this tRNA's anticodon stem and loop domain were determined with these modifications at positions 34, 37 and 39, respectively (hASL(Lys3)(UUU)-mcm(5)s(2)U(37);ms(2)t(6)A(37);ψ(39)). Ribosome binding assays in vitrorevealed that the hASL(Lys3)(UUU)-mcm(5)s(2)U(34);ms(2)t(6)A(37);ψ(39)bound AAA and AAG codons, whereas binding of the unmodified ASL(Lys3)(UUU) was barely detectable. The UV hyperchromicity, the circular dichroism and the structural analyses indicated that ψ(39) enhanced the thermodynamic stability of the ASL through base stacking while ms(2)t(6)A(37) restrained the anticodon to adopt an open loop conformation that is required for ribosomal binding. The NMR-restrained molecular dynamics derived solution structure revealed that the modifications provided an open, ordered loop for codon binding. The crystal structures of the hASL(Lys3)(UUU)-mcm(5)s(2)U(34);ms(2)t(6)A(37);ψ(39) bound to the 30S ribosomal subunit with each codon in the A site showed that the modified nucleotides mcm(5)s(2)U(34) and ms(2)t(6)A(37) participate in the stability of the anticodon/codon interaction. Importantly, the mcm(5)s(2)U(34)•G(3) wobble base pair is in the Watson-Crick geometry, requiring unusual hydrogen bonding to G in which mcm(5)s(2)U(34) must shift from the keto to enol form. The results unambiguously demonstrate that modifications pre-structurethe anticodonas a key prerequisite for efficient and accurate recognition of cognate and wobble codons.",,"['Vendeix, Franck A. P.', 'Murphy, Frank V.', 'Cantara, William A.', 'Leszczyńska, Grażyna', 'Gustilo, Estella M.', 'Sproat, Brian', 'Malkiewicz, Andrzej', 'Agris, Paul F.']",,,,
,PMC,Development of a DNA vaccine targeting Merkel cell polyomavirus,http://dx.doi.org/10.1016/j.vaccine.2011.12.072,PMC3784303,,,"Merkel cell carcinoma (MCC) is a rare but devastating skin disease that is increasing in incidence within the United States. The poor prognosis of MCC patients and limited understanding of MCC pathogenesis warrants innovative treatments to control MCC. Several lines of evidence have pointed to Merkel cell polyomavirus (MCPyV) as the etiological agent of MCC. In particular, the amino terminus of MCPyV large T antigen (LT) (aa1-258) is expressed in all MCPyV-positive tumors and plays an important role in MCC oncogenesis, rendering it an ideal therapeutic target for vaccination. In the current study, we developed a DNA vaccine encoding MCPyV LT aa1-258 (pcDNA3-LT). Within our pcDNA3-LT DNA vaccine, we identified that MCPyV LT aa136-160 likely contains an LT-specific CD4+ T helper epitope. We have also created an LT-expressing B16/LT tumor model using B16, a murine melanoma cell line, to characterize the potency of our DNA vaccine. Using this tumorigenic B16/LT tumor model, we found that pcDNA3-LT DNA vaccine generates antitumor effects mainly mediated by CD4+ T cells against B16/LT tumors in vaccinated C57BL/6 mice. Thus, immunotherapy using pcDNA3-LT DNA vaccine may represent a promising approach for the control of MCPyV-associated lesions. The B16/LT tumor model further serves as a useful model for testing various vaccine strategies against MCC.",,"['Zeng, Qi', 'Gomez, Bianca P.', 'Viscidi, Raphael P.', 'Peng, Shiwen', 'He, Liangmei', 'Ma, Barbara', 'Wu, T.C.', 'Hung, Chien-Fu']",,,,
,PMC,Regulation of the nucleocytoplasmic trafficking of viral and cellular proteins by ubiquitin and small ubiquitin-related modifiers,http://dx.doi.org/10.1111/boc.201100105,PMC3625690,,,"Nucleocytoplasmic trafficking of many cellular proteins is regulated by nuclear import/export signals as well as post-translational modifications such as covalent conjugation of ubiquitin and small ubiquitin-related modifiers (SUMOs). Ubiquitination and SUMOylation are rapid and reversible ways to modulate the intracellular localisation and function of substrate proteins. These pathways have been co-opted by some viruses, which depend on the host cell machinery to transport their proteins in and out of the nucleus. In this review, we will summarise our current knowledge on the ubiquitin/SUMO-regulated nuclear/subnuclear trafficking of cellular proteins and describe examples of viral exploitation of these pathways.",,"['Wang, Yao E.', 'Pernet, Olivier', 'Lee, Benhur']",,,,
,PMC,IL-27 promotes IL-10 production by effector Th1 CD4(+) T cells; a critical mechanism for protection from severe immunopathology during malaria infection(),http://dx.doi.org/10.4049/jimmunol.1102755,PMC3272378,,,"Infection with the malaria parasite, Plasmodium, is characterized by excessive inflammation. The establishment of a precise balance between the pro- and anti-inflammatory responses is critical to guarantee control of the parasite and survival of the host. Interleukin (IL)-10, a key regulatory cytokine produced by many cells of the immune system, has been shown to protect mice against pathology during acute Plasmodium chabaudi chabaudi AS model of malaria. However, the critical cellular source of IL-10 is still unknown. Here, we demonstrate that T cell-derived IL-10 is necessary for the control of pathology during acute malaria, as mice bearing specific deletion of Il10 in T cells fully reproduce the phenotype observed in Il10(−/−) mice, with significant weight loss, drop in temperature and increased mortality. Furthermore, we show that IFN-γ(+) Th1 cells are the main producers of IL-10 throughout acute infection, expressing high levels of CD44 and ICOS and low levels of CD127. Although Foxp3(+) regulatory CD4(+) T cells produce IL-10 during infection, highly activated IFN-γ(+) Th1 cells were shown to be the essential and sufficient source of IL-10 to guarantee protection against severe immune-mediated pathology. Finally, in this model of malaria we demonstrate that the generation of protective IL10(+)IFN-γ(+) Th1 cells is dependent on IL-27 signaling, and independent of IL-21.",,"['Freitas do Rosário, Ana Paula', 'Lamb, Tracey', 'Spence, Philip', 'Stephens, Robin', 'Lang, Agathe', 'Roers, Axel', 'Muller, Werner', 'O’Garra, Anne', 'Langhorne, Jean']",,,,
,PMC,Characterization of germline antibody libraries from human umbilical cord blood and selection of monoclonal antibodies to viral envelope glycoproteins: implications for mechanisms of immune evasion and design of vaccine immunogens,http://dx.doi.org/10.1016/j.bbrc.2011.12.089,PMC3268823,,,"We have previously observed that all known HIV-1 broadly neutralizing antibodies (bnAbs) are highly divergent from germline antibodies in contrast to bnAbs against Hendra virus, Nipah virus and SARS coronavirus (SARS CoV). We have hypothesized that because the germline antibodies are so different from the mature HIV-1-specific bnAbs they may not bind the epitopes of the mature antibodies and provided the first evidence to support this hypothesis by using individual putative germline-like predecessor antibodies. To further validate the hypothesis and understand initial immune responses to different viruses, two phage-displayed human cord blood-derived IgM libraries were constructed which contained mostly germline antibodies or antibodies with very low level of somatic hypermutations. They were panned against different HIV-1 envelope glycoproteins (Envs), SARS CoV protein receptor-binding domain (RBD), and soluble Hendra virus G protein (sG). Despite a high sequence and combinatorial diversity observed in the cord blood-derived IgM antibody repertoire, no enrichment for binders of Envs was observed in contrast to considerable specific enrichments produced with panning against RBD and sG; one of the selected monoclonal antibodies (against the RBD) was of high (nM) affinity with only few somatic mutations. These results further support and expand our initial hypothesis for fundamental differences in immune responses leading to elicitation of bnAbs against HIV-1 compared to SARS CoV and Hendra virus. HIV-1 uses a strategy to minimize or eliminate strong binding of germline antibodies to its Env; in contrast, SARS CoV and Hendra virus, and perhaps other viruses causing acute infections, can bind germline antibody or minimally somatically mutated antibodies with relatively high affinity which could be one of the reasons for the success of sG and RBD as vaccine immunogens.",,"['Chen, Weizao', 'Streaker, Emily D.', 'Russ, Daniel E.', 'Feng, Yang', 'Prabakaran, Ponraj', 'Dimitrov, Dimiter S.']",,,,
,PMC,Cytokines and brain excitability,http://dx.doi.org/10.1016/j.yfrne.2011.12.002,PMC3547977,,,"Cytokines are molecules secreted by peripheral immune cells, microglia, astrocytes and neurons in the central nervous system. Peripheral or central inflammation is characterized by an upregulation of cytokines and their receptors in the brain. Emerging evidence indicates that pro-inflammatory cytokines modulate brain excitability. Findings from both the clinical literature and from in vivo and in vitro laboratory studies suggest that cytokines can increase seizure susceptibility and may be involved in epileptogenesis. Cellular mechanisms that underlie these effects include upregulation of excitatory glutamatergic transmission and downregulation of inhibitory GABAergic transmission.",,"['Galic, Michael A.', 'Riazi, Kiarash', 'Pittman, Quentin J.']",,,,
,PMC,Characterization and inhibition of norovirus proteases of genogroups I and II using a fluorescence resonance energy transfer assay,http://dx.doi.org/10.1016/j.virol.2011.12.002,PMC3259199,,,"Noroviruses are the major cause of food- or water-borne gastroenteritis outbreaks in humans. The norovirus protease that cleaves a large viral polyprotein to nonstructural proteins is essential for virus replication and an attractive target for antiviral drug development. Noroviruses show high genetic diversity with at least five genogroups, GI–GV, of which GI and GII are responsible for the majority of norovirus infections in humans. We cloned and expressed proteases of Norwalk virus (GI) and MD145 virus (GII) and characterized the enzymatic activities with fluorescence resonance energy transfer substrates. We demonstrated that the GI and GII proteases cleaved the substrates derived from the naturally occurring cleavage site in the open reading frame (ORF) 1 of G1 norovirus with similar efficiency, and that enzymatic activity of both proteases were inhibited by commercial protease inhibitors including chymostatin. The interaction of chymostatin to Norwalk virus protease was validated by nuclear magnetic resonance (NMR) spectroscopy.",,"['Chang, Kyeong-Ok', 'Takahashi, Daisuke', 'Prakash, Om', 'Kim, Yunjeong']",,,,
,PMC,Validation of Self-swab for Virologic Confirmation of Influenza Virus Infections in a Community Setting,http://dx.doi.org/10.1093/infdis/jir803,PMC3266138,,,"Few studies have investigated the validity of self-collected nose and throat swabs for influenza confirmation in community settings. We followed outpatients with confirmed influenza with sequential measurement of viral loads and applied log-linear regression models to the viral shedding patterns. Among 176 outpatients with confirmed influenza, the detection of virus and quantitative viral loads obtained from self-swabs was consistent with statistical predictions based on earlier and later measurements, suggesting that self-collected nose and throat swabs can be a valid alternative for virologic confirmation of influenza A or B infection in a community setting.",,"['Ip, Dennis K. M.', 'Schutten, Martin', 'Fang, Vicky J.', 'Fung, Rita O. P.', 'Dutkowski, Regina T.', 'Chan, Kwok-Hung', 'Leung, Gabriel M.', 'Peiris, J. S. Malik', 'Cowling, Benjamin J.']",,,,
,PMC,Influenza A Viral Replication Is Blocked by Inhibition of the Inositol-requiring Enzyme 1 (IRE1) Stress Pathway,http://dx.doi.org/10.1074/jbc.M111.284695,PMC3281634,,,"Known therapies for influenza A virus infection are complicated by the frequent emergence of resistance. A therapeutic strategy that may escape viral resistance is targeting host cellular mechanisms involved in viral replication and pathogenesis. The endoplasmic reticulum (ER) stress response, also known as the unfolded protein response (UPR), is a primitive, evolutionary conserved molecular signaling cascade that has been implicated in multiple biological phenomena including innate immunity and the pathogenesis of certain viral infections. We investigated the effect of influenza A viral infection on ER stress pathways in lung epithelial cells. Influenza A virus induced ER stress in a pathway-specific manner. We showed that the virus activates the IRE1 pathway with little or no concomitant activation of the PERK and the ATF6 pathways. When we examined the effects of modulating the ER stress response on the virus, we found that the molecular chaperone tauroursodeoxycholic acid (TUDCA) significantly inhibits influenza A viral replication. In addition, a specific inhibitor of the IRE1 pathway also blocked viral replication. Our findings constitute the first evidence that ER stress plays a role in the pathogenesis of influenza A viral infection. Decreasing viral replication by modulating the host ER stress response is a novel strategy that has important therapeutic implications.",,"['Hassan, Ihab H.', 'Zhang, Michael S.', 'Powers, Linda S.', 'Shao, Jian Q.', 'Baltrusaitis, Jonas', 'Rutkowski, D. Thomas', 'Legge, Kevin', 'Monick, Martha M.']",,,,
,PMC,Progress Toward In Vivo Use of siRNAs-II,http://dx.doi.org/10.1038/mt.2011.263,PMC3293614,,,"RNA interference (RNAi) has been extensively employed for in vivo research since its use was first demonstrated in mammalian cells 10 years ago. Design rules have improved, and it is now routinely possible to obtain reagents that suppress expression of any gene desired. At the same time, increased understanding of the molecular basis of unwanted side effects has led to the development of chemical modification strategies that mitigate these concerns. Delivery remains the single greatest hurdle to widespread adoption of in vivo RNAi methods. However, exciting advances have been made and new delivery systems under development may help to overcome these barriers. This review discusses advances in RNAi biochemistry and biology that impact in vivo use and provides an overview of select publications that demonstrate interesting applications of these principles. Emphasis is placed on work with synthetic, small interfering RNAs (siRNAs) published since the first installment of this review which appeared in 2006.",,"['Rettig, Garrett R', 'Behlke, Mark A']",,,,
,PMC,Parkinson disease drug screening based on the interaction between D(2) dopamine receptor and beta-arrestin 2 detected by capillary zone electrophoresis,http://dx.doi.org/10.1007/s13238-011-1096-0,PMC4875183,,,"Parkinson’s disease is the second most common neurodegenerative disease in the world. Beta-arrestin-2 has been reported to be an important protein involved in D(2) dopamine receptor desensitization, which is essential to Parkinson’s disease. Moreover, the potential value of pharmacological inactivation of G protein-coupled receptor kinase or arrestin in the treatment of patients with Parkinson’s disease has recently been shown. We studied the interaction between D(2) dopamine receptor and beta-arrestin-2 and the pharmacological regulation of chemical compounds on such interaction using capillary zone electrophoresis. The results from screening more than 40 compounds revealed three compounds that remarkably inhibit the beta-arrestin-2/D(2) dopamine receptor interaction among them. These compounds are promising therapies for Parkinson’s disease, and the method used in this study has great potential for application in large-scale drug screening and evaluation.",,"['Zhou, Zheng', 'Liao, Jun-Ming', 'Zhang, Peng', 'Fan, Jun-Bao', 'Chen, Jie', 'Liang, Yi']",,,,
,PMC,Cytoskeletal defects in Bmpr2-associated pulmonary arterial hypertension,http://dx.doi.org/10.1152/ajplung.00202.2011,PMC3311512,,,"The heritable form of pulmonary arterial hypertension (PAH) is typically caused by a mutation in bone morphogenic protein receptor type 2 (BMPR2), and mice expressing Bmpr2 mutations develop PAH with features similar to human disease. BMPR2 is known to interact with the cytoskeleton, and human array studies in PAH patients confirm alterations in cytoskeletal pathways. The goal of this study was to evaluate cytoskeletal defects in BMPR2-associated PAH. Expression arrays on our Bmpr2 mutant mouse lungs revealed cytoskeletal defects as a prominent molecular consequence of universal expression of a Bmpr2 mutation (Rosa26-Bmpr2(R899X)). Pulmonary microvascular endothelial cells cultured from these mice have histological and functional cytoskeletal defects. Stable transfection of different BMPR2 mutations into pulmonary microvascular endothelial cells revealed that cytoskeletal defects are common to multiple BMPR2 mutations and are associated with activation of the Rho GTPase, Rac1. Rac1 defects are corrected in cell culture and in vivo through administration of exogenous recombinant human angiotensin-converting enzyme 2 (rhACE2). rhACE2 reverses 77% of gene expression changes in Rosa26-Bmpr2(R899X) transgenic mice, in particular, correcting defects in cytoskeletal function. Administration of rhACE2 to Rosa26-Bmpr2(R899X) mice with established PAH normalizes pulmonary pressures. Together, these findings suggest that cytoskeletal function is central to the development of BMPR2-associated PAH and that intervention against cytoskeletal defects may reverse established disease.",,"['Johnson, Jennifer A.', 'Hemnes, Anna R.', 'Perrien, Daniel S.', 'Schuster, Manfred', 'Robinson, Linda J.', 'Gladson, Santhi', 'Loibner, Hans', 'Bai, Susan', 'Blackwell, Tom R.', 'Tada, Yuji', 'Harral, Julie W.', 'Talati, Megha', 'Lane, Kirk B.', 'Fagan, Karen A.', 'West, James']",,,,
,PMC,Drosophila as a genetic model for studying pathogenic human viruses,http://dx.doi.org/10.1016/j.virol.2011.11.016,PMC3253880,,,"Viruses are infectious particles whose viability is dependent on the cells of living organisms, such as bacteria, plants, and animals. It is of great interest to discover how viruses function inside host cells in order to develop therapies to treat virally infected organisms. The fruit fly Drosophila melanogaster is an excellent model system for studying the molecular mechanisms of replication, amplification, and cellular consequences of human viruses. In this review, we describe the advantages of using Drosophila as a model system to study human viruses, and highlight how Drosophila has been used to provide unique insight into the gene function of several pathogenic viruses. We also propose possible directions for future research in this area.",,"['Hughes, Tamara T.', 'Allen, Amanda L.', 'Bardin, Joseph E.', 'Christian, Megan N.', 'Daimon, Kansei', 'Dozier, Kelsey D.', 'Hansen, Caom L.', 'Holcomb, Lisa M.', 'Ahlander, Joseph']",,,,
,PMC,Evaluation of two chimeric bovine-human parainfluenza virus type 3 vaccines in infants and young children,http://dx.doi.org/10.1016/j.vaccine.2011.12.022,PMC3509782,,,"Human parainfluenza virus type 3 (HPIV3) is an important cause of lower respiratory tract illness in children, yet a licensed vaccine or antiviral drug is not available. We evaluated the safety, tolerability, infectivity, and immunogenicity of two intranasal, live-attenuated HPIV3 vaccines, designated rHPIV3-N(B) and rB/HPIV3, that were cDNA-derived chimeras of HPIV3 and bovine PIV3 (BPIV3). These were evaluated in adults, HPIV3 seropositive children, and HPIV3 seronegative children. A total of 112 subjects participated in these studies. Both rB/HPIV3 and rHPIV3-N(B) were highly restricted in replication in adults and seropositive children but readily infected seronegative children, who shed mean peak virus titers of 10(2.8) vs. 10(3.7) pfu/mL, respectively. Although rB/HPIV3 was more restricted in replication in seronegative children than rHPIV3-N(B), it induced significantly higher titers of hemagglutination inhibition (HAI) antibodies against HPIV3. Taken together, these data suggest that the rB/HPIV3 vaccine is the preferred candidate for further clinical development.",,"['Karron, Ruth A.', 'Thumar, Bhagvanji', 'Schappell, Elizabeth', 'Surman, Sonja', 'Murphy, Brian R.', 'Collins, Peter L.', 'Schmidt, Alexander C.']",,,,
,PMC,Stability of bovine coronavirus on lettuce surfaces under household refrigeration conditions,http://dx.doi.org/10.1016/j.fm.2011.12.009,PMC4980993,,,"Fecal suspensions with an aerosol route of transmission were responsible for a cluster of severe acute respiratory syndrome (SARS) cases in 2003 in Hong Kong. Based on that event, the World Health Organization recommended that research be implemented to define modes of transmission of SARS coronavirus through sewage, feces, food and water. Environmental studies have shown that animal coronaviruses remain infectious in water and sewage for up to a year depending on the temperature and humidity. In this study, we examined coronavirus stability on lettuce surfaces. A cell culture adapted bovine coronavirus, diluted in growth media or in bovine fecal suspensions to simulate fecal contamination was used to spike romaine lettuce. qRT-PCR detected viral RNA copy number ranging from 6.6 × 10(4) to 1.7 × 10(6) throughout the experimental period of 30 days. Whereas infectious viruses were detected for at least 14 days, the amount of infectious virus varied, depending upon the diluent used for spiking the lettuce. UV and confocal microscopic observation indicated attachment of residual labeled virions to the lettuce surface after the elution procedure, suggesting that rates of inactivation or detection of the virus may be underestimated. Thus, it is possible that contaminated vegetables may be potential vehicles for coronavirus zoonotic transmission to humans.",,"['Mullis, Lisa', 'Saif, Linda J.', 'Zhang, Yongbin', 'Zhang, Xuming', 'Azevedo, Marli S.P.']",,,,
,PMC,Multiplexed Fluorometric ImmunoAssay Testing Methodology and Troubleshooting,http://dx.doi.org/10.3791/3715,PMC3679643,,,"To ensure the quality of animal models used in biomedical research we have developed a number of diagnostic testing strategies and methods to determine if animals have been exposed to adventitious infectious agents (viruses, mycoplasma, and other fastidious microorganisms). Infections of immunocompetent animals are generally transient, yet serum antibody responses to infection often can be detected within days to weeks and persist throughout the life of the host. Serology is the primary diagnostic methodology by which laboratory animals are monitored. Historically the indirect enzyme-linked immunosorbent assay (ELISA) has been the main screening method for serosurveillance. The ELISA is performed as a singleplex, in which one microbial antigen-antibody reaction is measured per well. In comparison the MFIA is performed as a multiplexed assay. Since the microspheres come in 100 distinct color sets, as many as 100 different assays can be performed simultaneously in a single microplate well. This innovation decreases the amount of serum, reagents and disposables required for routine testing while increasing the amount of information obtained from a single test well. In addition, we are able to incorporate multiple internal control beads to verify sample and system suitability and thereby assure the accuracy of results. These include tissue control and IgG anti-test serum species immunoglobulin (αIg) coated bead sets to evaluate sample suitability. As in the ELISA and IFA, the tissue control detects non-specific binding of serum immunoglobulin. The αIg control (Serum control) confirms that serum has been added and contains a sufficient immunoglobulin concentration while the IgG control bead (System Suitability control), coated with serum species immunoglobulin, demonstrates that the labeled reagents and Luminex reader are functioning properly.",,"['Wunderlich, Michelle L.', 'Dodge, Megan E.', 'Dhawan, Rajeev K.', 'Shek, William R.']",,,,
,PMC,Disease avoidance as a functional basis for stigmatization,http://dx.doi.org/10.1098/rstb.2011.0095,PMC3189356,,,"Stigmatization is characterized by chronic social and physical avoidance of a person(s) by other people. Infectious disease may produce an apparently similar form of isolation—disease avoidance—but on symptom remission this often abates. We propose that many forms of stigmatization reflect the activation of this disease-avoidance system, which is prone to respond to visible signs and labels that connote disease, irrespective of their accuracy. A model of this system is presented, which includes an emotional component, whereby visible disease cues directly activate disgust and contamination, motivating avoidance, and a cognitive component, whereby disease labels bring to mind disease cues, indirectly activating disgust and contamination. The unique predictions of this model are then examined, notably that people who are stigmatized evoke disgust and are contaminating. That animals too show avoidance of diseased conspecifics, and that disease-related stigma targets are avoided in most cultures, also supports this evolutionary account. The more general implications of this approach are then examined, notably how it can be used to good (e.g. improving hygiene) or bad (e.g. racial vilification) ends, by yoking particular labels with cues that connote disease and disgust. This broadening of the model allows for stigmatization of groups with little apparent connection to disease.",,"['Oaten, Megan', 'Stevenson, Richard J.', 'Case, Trevor I.']",,,,
,PMC,Improved proteomic approach for the discovery of potential vaccine targets in Trypanosoma cruzi,http://dx.doi.org/10.1021/pr200806s,PMC3253764,,,"Chagas disease, caused by Trypanosoma cruzi, is a devastating parasitic infection affecting millions of people. Although many efforts have been made for the development of immunotherapies, there is no available vaccine against this deadly infection. One major hurdle for the rational approach to develop a T. cruzi vaccine is the limited information about the proteins produced by different phylogenetic lineages, strains, and stages of the parasite. Here, we have adapted a 1D nanoHPLC system to perform online 2D LC-MS/MS, using the autosampler to inject the eluting salt solutions in the first dimension separation. The application of this methodology for the proteomic analysis of the infective trypomastigote stage of T. cruzi led to the identification of 1,448 non-redundant proteins. Furthermore, about 14% of the identified sequences comprise surface proteins, most of them glycosylphosphatidylinositol (GPI)-anchored and related to parasite pathogenesis. Immunoinformatic analysis revealed thousands of potential peptides with high affinity for major histocompatibility complex (MHC) class I and II presentation. The high diversity of proteins expressed on trypomastigote surface may have many implications for host-cell invasion and immunoevasion mechanisms triggered by the parasite. Finally, we performed a rational approach to filter potential epitopes that could be further tested and validated for development of a Chagas disease vaccine.",,"['Nakayasu, Ernesto S.', 'Sobreira, Tiago J. P.', 'Torres, Rafael', 'Ganiko, Luciane', 'Oliveira, Paulo S. L.', 'Marques, Alexandre F.', 'Almeida, Igor C.']",,,,
,PMC,Regulation by S-Nitrosylation of Protein Post-translational Modification,http://dx.doi.org/10.1074/jbc.R111.285742,PMC3281651,,,"Protein post-translational modification by S-nitrosylation conveys a ubiquitous influence of nitric oxide on signal transduction in eukaryotic cells. The wide functional purview of S-nitrosylation reflects in part the regulation by S-nitrosylation of the principal protein post-translational modifications that play a role in cell signaling, including phosphorylation, acetylation, ubiquitylation and related modifications, palmitoylation, and alternative Cys-based redox modifications. In this minireview, we discuss the mechanisms through which S-nitrosylation exerts its broad pleiotropic influence on protein post-translational modification.",,"['Hess, Douglas T.', 'Stamler, Jonathan S.']",,,,
,PMC,Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes(),http://dx.doi.org/10.4049/jimmunol.1102797,PMC3238790,,,"Immune complexes (ICs) play a pivotal role in causing inflammation in systemic lupus erythematosus (SLE)(). Yet, it remains unclear what the dominant blood cell type(s) and inflammation related gene programs stimulated by lupus ICs are. To address these questions, we exposed normal human peripheral blood mononuclear cells (PBMCs) or CD14(+) isolated monocytes to SLE ICs in the presence or absence of C1q and performed microarray analysis and other tests for cell activation. By microarray analysis, we identified genes and pathways regulated by SLE ICs that are both type I IFN dependent and independent. We also found that C1q containing ICs markedly reduced expression of the majority of IFN-response genes and also influenced the expression of multiple other genes induced by SLE ICs. Surprisingly, IC activation of isolated CD14(+) monocytes did not upregulate CD40 and CD86 and only modestly stimulated inflammatory gene expression. However, when monocyte subsets were purified and analyzed separately, the low abundance CD14(dim) (‘patrolling’) subpopulation was more responsive to ICs. These observations demonstrate the importance of plasmacytoid dendritic cells (pDCs), CD14(dim) monocytes and C1q as key regulators of inflammatory properties of ICs and identify many pathways through which they act.",,"['Santer, Deanna M.', 'Wiedeman, Alice E.', 'Teal, Thomas H.', 'Ghosh, Pradipta', 'Elkon, Keith B.']",,,,
,PMC,"Synthesis of benzopolycyclic cage amines: NMDA receptor antagonist, trypanocidal and antiviral activities",http://dx.doi.org/10.1016/j.bmc.2011.11.050,PMC3353318,,,"The synthesis of several 6,7,8,9,10,11-hexahydro-9-methyl-5,7:9,11-dimethano-5H-benzocyclononen-7-amines is reported. Several of them display low micromolar NMDA receptor antagonist and/or trypanocidal activities. Two compounds are endowed with micromolar anti vesicular stomatitis virus activity, while only one compound shows micromolar anti-influenza activity. The anti-influenza activity of this compound does not seem to be mediated by blocking of the M2 protein.",,"['Torres, Eva', 'Duque, María D.', 'López-Querol, Marta', 'Taylor, Martin C.', 'Naesens, Lieve', 'Ma, Chunlong', 'Pinto, Lawrence H.', 'Sureda, Francesc X.', 'Kelly, John M.', 'Vázquez, Santiago']",,,,
,PMC,Receptor Tyrosine Kinase Inhibitors That Block Replication of Influenza A and Other Viruses,http://dx.doi.org/10.1128/AAC.00725-11,PMC3232778,,,"We have previously reported that two receptor tyrosine kinase inhibitors (RTKIs), called AG879 and tyrphostin A9 (A9), can each block the replication of influenza A virus in cultured cells. In this study, we further characterized the in vitro antiviral efficacies and specificities of these agents. The 50% effective concentration (EC(50)) of each against influenza A was found to be in the high nanomolar range, and the selectivity index (SI = 50% cytotoxic concentration [CC(50)]/EC(50)) was determined to be >324 for AG879 and 50 for A9, indicating that therapeutically useful concentrations of each drug produce only low levels of cytotoxicity. Each compound showed efficacy against representative laboratory strains of both human influenza A (H1N1 or H3N2) and influenza B viruses. Importantly, no drug-resistant influenza virus strains emerged even after 25 viral passages in the presence of AG879, whereas viruses resistant to amantadine appeared after only 3 passages. AG879 and A9 each also exhibited potent inhibitory activity against a variety of other RNA and DNA viruses, including Sendai virus (Paramyxoviridae), herpes simplex virus (Herpesviridae), mouse hepatitis virus (Coronaviridae), and rhesus rotavirus (Reoviridae), but not against Pichinde virus (Arenaviridae). These results together suggest that RTKIs may be useful as therapeutics against viral pathogens, including but not limited to influenza, due to their high selectivity indices, low frequency of drug resistance, and broad-spectrum antiviral activities.",,"['Kumar, Naveen', 'Sharma, Nishi R.', 'Ly, Hinh', 'Parslow, Tristram G.', 'Liang, Yuying']",,,,
,PMC,Vaccinia virus leads to ATG12–ATG3 conjugation and deficiency in autophagosome formation,http://dx.doi.org/10.4161/auto.7.12.17793,PMC3327614,,,"The interactions between viruses and cellular autophagy have been widely reported. On the one hand, autophagy is an important innate immune response against viral infection. On the other hand, some viruses exploit the autophagy pathway for their survival and proliferation in host cells. Vaccinia virus is a member of the family of Poxviridae which includes the smallpox virus. The biogenesis of vaccinia envelopes, including the core envelope of the immature virus (IV), is not fully understood. In this study we investigated the possible interaction between vaccinia virus and the autophagy membrane biogenesis machinery. Massive LC3 lipidation was observed in mouse fibroblast cells upon vaccinia virus infection. Surprisingly, the vaccinia virus induced LC3 lipidation was shown to be independent of ATG5 and ATG7, as the atg5 and atg7 null mouse embryonic fibroblasts (MEFs) exhibited the same high levels of LC3 lipidation as compared with the wild-type MEFs. Mass spectrometry and immunoblotting analyses revealed that the viral infection led to the direct conjugation of ATG3, which is the E2-like enzyme required for LC3-phosphoethanonamine conjugation, to ATG12, which is a component of the E3-like ATG12–ATG5-ATG16 complex for LC3 lipidation. Consistently, ATG3 was shown to be required for the vaccinia virus induced LC3 lipidation. Strikingly, despite the high levels of LC3 lipidation, subsequent electron microscopy showed that vaccinia virus-infected cells were devoid of autophagosomes, either in normal growth medium or upon serum and amino acid deprivation. In addition, no autophagy flux was observed in virus-infected cells. We further demonstrated that neither ATG3 nor LC3 lipidation is crucial for viral membrane biogenesis or viral proliferation and infection. Together, these results indicated that vaccinia virus does not exploit the cellular autophagic membrane biogenesis machinery for their viral membrane production. Moreover, this study demonstrated that vaccinia virus instead actively disrupts the cellular autophagy through a novel molecular mechanism that is associated with aberrant LC3 lipidation and a direct conjugation between ATG12 and ATG3.",,"['Moloughney, Joseph G.', 'Monken, Claude E.', 'Tao, Hanlin', 'Zhang, Haiyan', 'Thomas, Janice D.', 'Lattime, Edmund C.', 'Jin, Shengkan']",,,,
,PMC,Scientists embrace the “One World” approach,http://dx.doi.org/10.2471/BLT.11.031211,PMC3260892,,,"Public and political awareness of emerging infectious diseases is growing, as animal and human health specialists work closer together to avert potential outbreaks. Fiona Fleck and Theresa Braine report.",,,,,,
,PMC,Top of the list,,PMC3237503,,,,,"Pimlott, Nicholas",,,,
,PMC,Virus-Like Particle Vaccine Containing Hemagglutinin Confers Protection against 2009 H1N1 Pandemic Influenza,http://dx.doi.org/10.1128/CVI.05206-11,PMC3232700,,,"Immunization of the world population before an influenza pandemic such as the 2009 H1N1 virus spreads globally is not possible with current vaccine production platforms. New influenza vaccine technologies, such as virus-like-particles (VLPs), offer a promising alternative. Here, we tested the immunogenicity and protective efficacy of a VLP vaccine containing hemagglutinin (HA) and M1 from the 2009 pandemic H1N1 influenza virus (H1N1pdm) in ferrets and compared intramuscular (i.m.) and intranasal (i.n.) routes of immunization. Vaccination of ferrets with VLPs containing the M1 and HA proteins from A/California/04/2009 (H1N1pdm) induced high antibody titers and conferred significant protection against virus challenge. VLP-vaccinated animals lost less weight, shed less virus in nasal washes, and had markedly lower virus titers in all organs tested than naïve controls. A single dose of VLPs, either i.m. or i.n., induced higher levels of antibody than did two doses of commercial split vaccine. Ferrets vaccinated with split vaccine were incompletely protected against challenge; these animals had lower virus titers in olfactory bulbs, tonsils, and intestines, but lost weight and shed virus in nasal washes to a similar extent as naïve controls. Challenge with heterologous A/Brisbane/59/07 (H1N1) virus revealed that the VLPs conferred minimal cross-protection to heterologous infection, as revealed by the lack of reduction in nasal wash and lung virus titers and slightly higher weight loss relative to controls. In summary, these experiments demonstrate the strong immunogenicity and protective efficacy of VLPs compared to the split vaccine and show that i.n. vaccination with VLPs has the potential for highly efficacious vaccination against influenza.",,"['Hossain, M. Jaber', 'Bourgeois, Melissa', 'Quan, Fu-Shi', 'Lipatov, Aleksandr S.', 'Song, Jae-Min', 'Chen, Li-Mei', 'Compans, Richard W.', 'York, Ian', 'Kang, Sang-Moo', 'Donis, Ruben O.']",,,,
,PMC,Interferon-stimulated genes and their antiviral effector functions,http://dx.doi.org/10.1016/j.coviro.2011.10.008,PMC3274382,,,"Many viruses trigger the type I interferon (IFN) system, leading to the transcription of hundreds of interferon-stimulated genes (ISGs). The products of these ISGs exert numerous antiviral effector functions, many of which are still not fully described. Recent efforts have been aimed at identifying which ISGs are antiviral and further characterizing their mechanisms of action. IFN effectors vary widely in their magnitude of inhibitory activity and display combinatorial antiviral properties. Collectively, ISGs can target almost any step in a virus life cycle. Some of the most potent antiviral effectors reinforce the system by further inducing IFN or ISGs. Other genes enhance or facilitate viral replication, suggesting that some viruses may have evolved to co-opt IFN effectors for a survival advantage.",,"['Schoggins, John W.', 'Rice, Charles M.']",,,,
,PMC,SARS-CoV and Emergent Coronaviruses: Viral Determinants of Interspecies Transmission,http://dx.doi.org/10.1016/j.coviro.2011.10.012,PMC3237677,,,"Most new emerging viruses are derived from strains circulating in zoonotic reservoirs. Coronaviruses, which had an established potential for cross-species transmission within domesticated animals, suddenly became relevant with the unexpected emergence of the highly pathogenic human SARS-CoV strain from zoonotic reservoirs in 2002. SARS-CoV infected approximately 8000 people worldwide before public health measures halted the epidemic. Supported by robust time-ordered sequence variation, structural biology, well-characterized patient pools, and biological data, the emergence of SARS-CoV represents one of the best studied natural models of viral disease emergence from zoonotic sources. This review article summarizes previous and more recent advances into the molecular and structural characteristics, with particular emphasis on host-receptor interactions, that drove this remarkable virus disease outbreak in human populations.",,"['Bolles, Meagan', 'Donaldson, Eric', 'Baric, Ralph']",,,,
,PMC,Enhancing the Teaching of Evolution in Public Health,http://dx.doi.org/10.1007/s12052-011-0382-x,PMC4160022,,,"SUMMARY: Public health courses are emerging as popular undergraduate offerings, especially at universities with schools of public health. It is important to note that evolution has shaped the burden of disease in the modern world in which we practice and educate for public health. Human cultures and technologies have modified life on Planet Earth and have co-evolved with myriad other species, including microorganisms, plant and animal sources of food, invertebrate vectors of disease, and intermediate bird, mammal, and primate hosts. Molecular mechanisms of evolution have produced differential resistance or susceptibility to infectious agents, including malaria, plague, smallpox, TB, measles, and diarrheal and respiratory diseases. The domestication of sheep and cattle led to natural selection in favor of human populations able to digest milk throughout life through persistence into adulthood of lactase enzyme expression in the intestine, a major story of anthropology. The emergence of a “Western diet” of dairy, refined cereal grains, refined sugars, vegetable oils, alcoholic beverages, salt, and omega-6-rich meats has dramatically altered glycemic load, fatty acid composition, macro-nutrients, acid-base balance, sodium/potassium ratio, and fiber content. This is a major story of nutrition and disease. The results include epidemics of atherosclerotic cardiovascular disease, obesity, diabetes, high blood pressure, osteoporosis, certain cancers, and bowel, inflammatory, and autoimmune disorders. Another interesting phenomenon is the selection of excessive hemostatic activity from platelets and the plasma clotting proteins; what was protective against death from bleeding after injuries among hunter-gatherers or from pregnancy-related hemorrhage now contributes to thrombosis underlying heart attacks and strokes. Conversely, there is little pressure against hemostasis and thrombosis since deaths from these causes occur mostly after the reproductive years of life. Learning about evolution over millennia for humans and over hours or days for microbes enlivens the experience of understanding evolutionary biology in public health context.",,"Omenn, Gilbert S.",,,,
,PMC,The emerging relationship between the airway microbiota and chronic respiratory disease: clinical implications,http://dx.doi.org/10.1586/ers.11.76,PMC3359942,,,"Until recently, relationships between evidence of colonization or infection by specific microbial species and the development, persistence or exacerbation of pulmonary disease have informed our opinions of airway microbiology. However, recent applications of culture-independent tools for microbiome profiling have revealed a more diverse microbiota than previously recognized in the airways of patients with chronic pulmonary disease. New evidence indicates that the composition of airway microbiota differs in states of health and disease and with severity of symptoms and that the microbiota, as a collective entity, may contribute to pathophysiologic processes associated with chronic airway disease. Here, we review the evolution of airway microbiology studies of chronic pulmonary disease, focusing on asthma, chronic obstructive pulmonary disease and cystic fibrosis. Building on evidence derived from traditional microbiological approaches and more recent culture-independent microbiome studies, we discuss the implications of recent findings on potential microbial determinants of respiratory health or disease.",,"['Huang, Yvonne J', 'Lynch, Susan V']",,,,
,PMC,Epitope Characterization of Sero-Specific Monoclonal Antibody to Clostridium botulinum Neurotoxin Type A,http://dx.doi.org/10.1089/hyb.2011.0032,PMC3278809,,,"Botulinum neurotoxins (BoNTs) are extremely potent toxins that can contaminate foods and are a public health concern. Anti-BoNT antibodies have been described that are capable of detecting BoNTs; however there still exists a need for accurate and sensitive detection capabilities for BoNTs. Herein, we describe the characterization of a panel of eight monoclonal antibodies (MAbs) generated to the non-toxic receptor-binding domain of BoNT/A (H(C)50/A) developed using a high-throughput screening approach. In two independent hybridoma fusions, two groups of four IgG MAbs were developed against recombinant H(C)50/A. Of these eight, only a single MAb, F90G5-3, bound to the whole BoNT/A protein and was characterized further. The F90G5-3 MAb slightly prolonged time to death in an in vivo mouse bioassay and was mapped by pepscan to a peptide epitope in the N-terminal subdomain of H(C)50/A (H(CN)25/A) comprising amino acid residues (985)WTLQDTQEIKQRVVF(999), an epitope that is highly immunoreactive in humans. Furthermore, we demonstrate that F90G5-3 binds BoNT/A with nanomolar efficiency. Together, our results indicate that F90G5-3 is of potential value as a diagnostic immunoreagent for BoNT/A capture assay development and bio-forensic analysis.",,"['Corbett, Cindi R.', 'Ballegeer, Erin', 'Weedmark, Kelly A.', 'Elias, M.D.', 'Al-Saleem, Fetweh H.', 'Ancharski, Denise M.', 'Simpson, Lance L.', 'Berry, Jody D.']",,,,
,PMC,Comparison of the FilmArray Respiratory Panel and Prodesse Real-Time PCR Assays for Detection of Respiratory Pathogens,http://dx.doi.org/10.1128/JCM.05010-11,PMC3232999,,,"We compared the diagnostic performance and overall respiratory pathogen detection rate of the premarket version of the FilmArray Respiratory Panel (RP) multiplex PCR assay (Idaho Technology, Inc., Salt Lake City, UT) with those of the Food and Drug Administration (FDA)-cleared Prodesse ProFlu+, ProFAST+, ProParaflu+, Pro hMPV+, and ProAdeno+ real-time PCR assays (Gen-Probe, San Diego, CA). The assays were performed on a panel of 192 nasopharyngeal-secretion specimens collected from 81 children under 1 year of age with upper respiratory tract symptoms. To resolve discordant results and confirm pathogens detected only by the larger FilmArray panel, we performed laboratory-developed real-time PCR assays. Among viruses detectable by both commercial assays (adenovirus, human metapneumovirus, influenza A virus, influenza B virus, parainfluenza viruses 1 to 3, and respiratory syncytial virus), the FilmArray and Prodesse assays showed good overall agreement (181/192 [94.3%]; kappa = 0.87; 95% CI, 0.79 to 0.94). FilmArray RP detected more parainfluenza viruses 1 and 3 than ProParaflu+ (18 versus 13) while ProAdeno+ detected more adenoviruses (11 versus 6), but these differences were not statistically significant. Additionally, FilmArray RP detected 138 pathogens (confirmed as true positives) not included in the Prodesse assays (rhinovirus [RV]/enterovirus [EV], 118; bocavirus, 8; coronavirus, 7; parainfluenza virus 4, 4; Mycoplasma pneumoniae, 1). FilmArray RP was cleared by the FDA following the completion of this study. The FDA-cleared version includes the following targets: adenovirus, coronaviruses HKU1 and NL63, human metapneumovirus (hMPV), influenza A virus (to type level only), influenza A H1 seasonal virus, influenza A H3 seasonal virus, influenza A virus H1-2009, influenza B virus, parainfluenza viruses 1 to 4, respiratory syncytial virus (RSV), and RV/EV (no differentiation). The larger panel in the FilmArray RP assay allowed the detection of additional respiratory pathogens compared to the Prodesse assays. In this population of young children with upper respiratory tract infection, RV/EV accounted for the majority of the additional pathogens detected by FilmArray RP.",,"['Loeffelholz, M. J.', 'Pong, D. L.', 'Pyles, R. B.', 'Xiong, Y.', 'Miller, A. L.', 'Bufton, K. K.', 'Chonmaitree, T.']",,,,
,PMC,The Challenges and Opportunities of Teaching “Generation Y”,http://dx.doi.org/10.4300/JGME-03-04-15,PMC3244307,,,,,"['Eckleberry-Hunt, Jodie', 'Tucciarone, Jennifer']",,,,
,PMC,Chinese Guidelines for Diagnosis and Treatment of Influenza (2011),http://dx.doi.org/10.3978/j.issn.2072-1439.2011.10.01,PMC3256530,,,,,"['Zhong, Nan-shan', 'Li, Yi-min', 'Yang, Zi-feng', 'Wang, Chen', 'Liu, You-ning', 'Li, Xing-wang', 'Shu, Yue-long', 'Wang, Guang-fa', 'Gao, Zhan-cheng', 'Deng, Guo-hua', 'He, Li-xian', 'Xi, Xiu-ming', 'Cao, Bin', 'Shen, Kun-ling', 'Wu, Hao', 'Zhou, Ping-an', 'Li, Qing-quan', None]",,,,
,PMC,Pandemic H1N1 influenza,http://dx.doi.org/10.3978/j.issn.2072-1439.2011.08.05,PMC3256529,,,"The 2009 H1N1 influenza A virus that has targeted not only those with chronic medical illness, the very young and old, but also a large segment of the patient population that has previously been afforded relative protection - those who are young, generally healthy, and immune naive. The illness is mild in most, but results in hospitalization and severe ARDS in an important minority. Among those who become critically ill, 20-40% will die, predominantly of severe hypoxic respiratory failure. However, and potentially in part due to the young age of those affected, intensive care with aggressive oxygenation support will allow most people to recover. The volume of patients infected and with critical illness placed substantial strain on the capacity of the health care system and critical care most specifically. Despite this, the 2009 pandemic has engaged our specialty and highlighted its importance like no other. Thus far, the national and global critical care response has been brisk, collaborative and helpful - not only for this pandemic, but for subsequent challenges in years ahead.",,"Kumar, Anand",,,,
,PMC,Genome-Wide Association Study among Four Horse Breeds Identifies a Common Haplotype Associated with In Vitro CD3(+) T Cell Susceptibility/Resistance to Equine Arteritis Virus Infection,http://dx.doi.org/10.1128/JVI.06068-11,PMC3233183,,,"Previously, we have shown that horses could be divided into susceptible and resistant groups based on an in vitro assay using dual-color flow cytometric analysis of CD3(+) T cells infected with equine arteritis virus (EAV). Here, we demonstrate that the differences in in vitro susceptibility of equine CD3(+) T lymphocytes to EAV infection have a genetic basis. To investigate the possible hereditary basis for this trait, we conducted a genome-wide association study (GWAS) to compare susceptible and resistant phenotypes. Testing of 267 DNA samples from four horse breeds that had a susceptible or a resistant CD3(+) T lymphocyte phenotype using both Illumina Equine SNP50 BeadChip and Sequenom's MassARRAY system identified a common, genetically dominant haplotype associated with the susceptible phenotype in a region of equine chromosome 11 (ECA11), positions 49572804 to 49643932. The presence of a common haplotype indicates that the trait occurred in a common ancestor of all four breeds, suggesting that it may be segregated among other modern horse breeds. Biological pathway analysis revealed several cellular genes within this region of ECA11 encoding proteins associated with virus attachment and entry, cytoskeletal organization, and NF-κB pathways that may be associated with the trait responsible for the in vitro susceptibility/resistance of CD3(+) T lymphocytes to EAV infection. The data presented in this study demonstrated a strong association of genetic markers with the trait, representing de facto proof that the trait is under genetic control. To our knowledge, this is the first GWAS of an equine infectious disease and the first GWAS of equine viral arteritis.",,"['Go, Yun Young', 'Bailey, Ernest', 'Cook, Deborah G.', 'Coleman, Stephen J.', 'MacLeod, James N.', 'Chen, Kuey-Chu', 'Timoney, Peter J.', 'Balasuriya, Udeni B. R.']",,,,
,PMC,Cleavage and Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by Human Airway Trypsin-Like Protease,http://dx.doi.org/10.1128/JVI.05300-11,PMC3233180,,,"The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) poses a constant threat to human health. The viral spike protein (SARS-S) mediates host cell entry and is a potential target for antiviral intervention. Activation of SARS-S by host cell proteases is essential for SARS-CoV infectivity but remains incompletely understood. Here, we analyzed the role of the type II transmembrane serine proteases (TTSPs) human airway trypsin-like protease (HAT) and transmembrane protease, serine 2 (TMPRSS2), in SARS-S activation. We found that HAT activates SARS-S in the context of surrogate systems and authentic SARS-CoV infection and is coexpressed with the viral receptor angiotensin-converting enzyme 2 (ACE2) in bronchial epithelial cells and pneumocytes. HAT cleaved SARS-S at R667, as determined by mutagenesis and mass spectrometry, and activated SARS-S for cell-cell fusion in cis and trans, while the related pulmonary protease TMPRSS2 cleaved SARS-S at multiple sites and activated SARS-S only in trans. However, TMPRSS2 but not HAT expression rendered SARS-S-driven virus-cell fusion independent of cathepsin activity, indicating that HAT and TMPRSS2 activate SARS-S differentially. Collectively, our results show that HAT cleaves and activates SARS-S and might support viral spread in patients.",,"['Bertram, Stephanie', 'Glowacka, Ilona', 'Müller, Marcel A.', 'Lavender, Hayley', 'Gnirss, Kerstin', 'Nehlmeier, Inga', 'Niemeyer, Daniela', 'He, Yuxian', 'Simmons, Graham', 'Drosten, Christian', 'Soilleux, Elizabeth J.', 'Jahn, Olaf', 'Steffen, Imke', 'Pöhlmann, Stefan']",,,,
,PMC,Genomic Sequencing and Characterization of Cynomolgus Macaque Cytomegalovirus,http://dx.doi.org/10.1128/JVI.05840-11,PMC3233177,,,"Cytomegalovirus (CMV) infection is the most common opportunistic infection in immunosuppressed individuals, such as transplant recipients or people living with HIV/AIDS, and congenital CMV is the leading viral cause of developmental disabilities in infants. Due to the highly species-specific nature of CMV, animal models that closely recapitulate human CMV (HCMV) are of growing importance for vaccine development. Here we present the genomic sequence of a novel nonhuman primate CMV from cynomolgus macaques (Macaca fascicularis; CyCMV). CyCMV (Ottawa strain) was isolated from the urine of a healthy, captive-bred, 4-year-old cynomolgus macaque of Philippine origin, and the viral genome was sequenced using next-generation Illumina sequencing to an average of 516-fold coverage. The CyCMV genome is 218,041 bp in length, with 49.5% G+C content and 84% protein-coding density. We have identified 262 putative open reading frames (ORFs) with an average coding length of 789 bp. The genomic organization of CyCMV is largely colinear with that of rhesus macaque CMV (RhCMV). Of the 262 CyCMV ORFs, 137 are homologous to HCMV genes, 243 are homologous to RhCMV 68.1, and 200 are homologous to RhCMV 180.92. CyCMV encodes four ORFs that are not present in RhCMV strain 68.1 or 180.92 but have homologies with HCMV (UL30, UL74A, UL126, and UL146). Similar to HCMV, CyCMV does not produce the RhCMV-specific viral homologue of cyclooxygenase-2. This newly characterized CMV may provide a novel model in which to study CMV biology and HCMV vaccine development.",,"['Marsh, Angie K.', 'Willer, David O.', 'Ambagala, Aruna P. N.', 'Dzamba, Misko', 'Chan, Jacqueline K.', 'Pilon, Richard', 'Fournier, Jocelyn', 'Sandstrom, Paul', 'Brudno, Michael', 'MacDonald, Kelly S.']",,,,
,PMC,A Virion-Associated Protein Kinase Induces Apoptosis,http://dx.doi.org/10.1128/JVI.05294-11,PMC3233169,,,"Apoptosis and inhibition of host gene expression are often associated with virus infections. Many viral polypeptides modulate apoptosis by direct interaction with highly conserved apoptotic pathways. Some viruses induce apoptosis during late stages of the infection cycle, while others inhibit apoptosis to facilitate replication or maintain persistent infection. In previous work, we showed that Chilo iridescent virus (CIV) or CIV virion protein extract induces apoptosis in spruce budworm and cotton boll weevil cell cultures. Here, we characterize the product of a CIV gene (iridovirus serine/threonine kinase; istk) with signature sequences for S/T kinase and ATP binding. ISTK appears to belong to the superfamily, vaccinia-related kinases (VRKs). The istk gene was expressed in Pichia pastoris vectors. Purified ISTK (48 kDa) exhibited S/T kinase activity. Treatment with ISTK induced apoptosis in budworm cells. A 35-kDa cleavage product of ISTK retaining key signature sequences was identified during purification. Pichia-expressed 35-kDa polypeptide, designated iridoptin, induced apoptosis and inhibition of host protein synthesis in budworm and boll weevil cells. A mutation in the ATP-binding site eliminated both kinase and apoptosis activity of iridoptin, suggesting that kinase activity is essential for induction of apoptosis. Analysis with custom antibody confirmed that ISTK is a structural component of CIV particles. This is the first demonstration of a viral kinase inducing apoptosis in any virus-host system and the first identification of a factor inducing apoptosis or host protein shutoff for the family Iridoviridae.",,"['Chitnis, Nilesh S.', 'Paul, Eric R.', 'Lawrence, Paulraj K.', 'Henderson, Curtis W.', 'Ganapathy, Saranya', 'Taylor, Patrick V.', 'Virdi, Kamaldeep S.', 'D’Costa, Susan M.', 'May, Ashley R.', 'Bilimoria, Shan L.']",,,,
,PMC,Cellular Poly(C) Binding Proteins 1 and 2 Interact with Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 1β and Support Viral Replication,http://dx.doi.org/10.1128/JVI.05177-11,PMC3233143,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) infection of swine results in substantial economic losses to the swine industry worldwide. Identification of cellular factors involved in PRRSV life cycle not only will enable a better understanding of virus biology but also has the potential for the development of antiviral therapeutics. The PRRSV nonstructural protein 1 (nsp1) has been shown to be involved in at least two important functions in the infected hosts: (i) mediation of viral subgenomic (sg) mRNA transcription and (ii) suppression of the host's innate immune response mechanisms. To further our understanding of the role of the viral nsp1 in these processes, using nsp1β, a proteolytically processed functional product of nsp1 as bait, we have identified the cellular poly(C)-binding proteins 1 and 2 (PCBP1 and PCBP2) as two of its interaction partners. The interactions of PCBP1 and PCBP2 with nsp1β were confirmed both by coimmunoprecipitation in infected cells and/or in plasmid-transfected cells and also by in vitro binding assays. During PRRSV infection of MARC-145 cells, the cytoplasmic PCBP1 and PCBP2 partially colocalize to the viral replication-transcription complexes. Furthermore, recombinant purified PCBP1 and PCBP2 were found to bind the viral 5′ untranslated region (5′UTR). Small interfering RNA (siRNA)-mediated silencing of PCBP1 and PCBP2 in cells resulted in significantly reduced PRRSV genome replication and transcription without adverse effect on initial polyprotein synthesis. Overall, the results presented here point toward an important role for PCBP1 and PCBP2 in regulating PRRSV RNA synthesis.",,"['Beura, Lalit K.', 'Dinh, Phat X.', 'Osorio, Fernando A.', 'Pattnaik, Asit K.']",,,,
,PMC,ISG56 and IFITM1 Proteins Inhibit Hepatitis C Virus Replication,http://dx.doi.org/10.1128/JVI.05633-11,PMC3233139,,,"Hepatitis C virus (HCV) often leads to persistent infection. Interferon (IFN) and IFN-stimulated genes (ISGs) are amplified during HCV infection but fail to eliminate virus from the liver in a large number of infected patients. We have observed previously that HCV infection induces IFN-β production in immortalized human hepatocytes (IHH) as early as 24 h after infection, although virus replication is not inhibited. To gain insights on possible countermeasures of virus for the suppression of host antiviral response, the cellular transcriptional profiles of ISGs were examined after various treatments of IHH. The majority of ISGs were upregulated in IFN-treated IHH from the level for mock-treated cells. However, the comparison of ISG expression in IFN-treated IHH and IFN-pretreated, HCV genotype 2a-infected IHH indicated that virus infection suppresses the upregulation of a subset of effector molecules, including ISG56 and IFITM1. Similar results were observed for HCV-infected Huh7 cells. Subsequent study suggested that the exogenous expression of ISG56 or IFITM1 inhibits HCV replication in IHH or Huh7 cells, and the knockdown of these genes enhanced HCV replication. Further characterization revealed that the overexpression of these ISGs does not block HCV pseudotype entry into Huh7 cells. Taken together, our results demonstrated that ISG56 and IFITM1 serve as important molecules to restrict HCV infection, and they may have implications in the development of therapeutic modalities.",,"['Raychoudhuri, Amit', 'Shrivastava, Shubham', 'Steele, Robert', 'Kim, Hangeun', 'Ray, Ranjit', 'Ray, Ratna B.']",,,,
,PMC,Poliovirus Unlinks TIA1 Aggregation and mRNA Stress Granule Formation,http://dx.doi.org/10.1128/JVI.05888-11,PMC3209409,,,"In response to environmental stress and viral infection, mammalian cells form foci containing translationally silenced mRNPs termed stress granules (SGs). As aggregates of stalled initiation complexes, SGs are defined by the presence of translation initiation machinery in addition to mRNA binding proteins. Here, we report that cells infected with poliovirus (PV) can form SGs early that contain T-cell-restricted intracellular antigen 1 (TIA1), translation initiation factors, RNA binding proteins, and mRNA. However, this response is blocked as infection progresses, and a type of pseudo-stress granule remains at late times postinfection and contains TIA but lacks translation initiation factors, mRNA binding proteins, and most polyadenylated mRNA. This result was observed using multiple stressors, including viral infection, oxidative stress, heat shock, and endoplasmic reticulum stress. Multiple proteins required for efficient viral internal ribosome entry site-dependent translation are localized to SGs under stress conditions, providing a potential rationale for the evolution and maintenance of the SG inhibition phenotype. Further, the expression of a noncleavable form of the RasGAP-SH3 domain binding protein in PV-infected cells enables SGs whose constituents are consistent with the presence of stalled 48S translation preinitiation complexes to persist throughout infection. These results indicate that in poliovirus-infected cells, the functions of TIA self-aggregation and aggregation of stalled translation initiation complexes into stress granules are severed, leading to novel foci that contain TIA1 but lack other stress granule-defining components.",,"['White, James P.', 'Lloyd, Richard E.']",,,,
,PMC,Glutamate Excitotoxicity Is Involved in the Induction of Paralysis in Mice after Infection by a Human Coronavirus with a Single Point Mutation in Its Spike Protein,http://dx.doi.org/10.1128/JVI.05576-11,PMC3209392,,,"Human coronaviruses (HCoV) are recognized respiratory pathogens, and some strains, including HCoV-OC43, can infect human neuronal and glial cells of the central nervous system (CNS) and activate neuroinflammatory mechanisms. Moreover, HCoV-OC43 is neuroinvasive, neurotropic, and neurovirulent in susceptible mice, where it induces chronic encephalitis. Herein, we show that a single point mutation in the viral spike (S) glycoprotein (Y241H), acquired during viral persistence in human neural cells, led to a hind-limb paralytic disease in infected mice. Inhibition of glutamate excitotoxicity using a 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propranoic acid (AMPA) receptor antagonist (GYKI-52466) improved clinical scores related to the paralysis and motor disabilities in S mutant virus-infected mice, as well as protected the CNS from neuronal dysfunctions, as illustrated by restoration of the phosphorylation state of neurofilaments. Expression of the glial glutamate transporter GLT-1, responsible for glutamate homeostasis, was downregulated following infection, and GYKI-52466 also significantly restored its steady-state expression level. Finally, GYKI-52466 treatment of S mutant virus-infected mice led to reduced microglial activation, which may lead to improvement in the regulation of CNS glutamate homeostasis. Taken together, our results strongly suggest an involvement of excitotoxicity in the paralysis-associated neuropathology induced by an HCoV-OC43 mutant which harbors a single point mutation in its spike protein that is acquired upon persistent virus infection.",,"['Brison, Elodie', 'Jacomy, Hélène', 'Desforges, Marc', 'Talbot, Pierre J.']",,,,
,PMC,Rotavirus Infection Induces the Unfolded Protein Response of the Cell and Controls It through the Nonstructural Protein NSP3,http://dx.doi.org/10.1128/JVI.05620-11,PMC3209385,,,"The unfolded protein response (UPR) is a cellular mechanism that is triggered in order to cope with the stress caused by the accumulation of misfolded proteins in the endoplasmic reticulum (ER). This response is initiated by the endoribonuclease inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), and PKR-like ER kinase, which increase the expression of the genes involved in the folding and degradation processes and decrease the protein input into the ER by inhibiting translation. It has been shown that viruses both induce and manipulate the UPR in order to protect the host cells from an ER stress-mediated death, thus permitting the translation of viral proteins and the efficient replication of the virus. To understand the cellular events that occur during the rotavirus replication cycle, we examined the activation of the three UPR arms following infection, using luciferase reporters driven by promoters of the ER stress-responsive genes and real-time reverse transcription-PCR to determine the levels of the stress-induced mRNAs. Our findings indicated that during rotavirus infection two of the three arms of the UPR (IRE1 and ATF6) become activated; however, these pathways are interrupted at the translational level by the general inhibition of protein synthesis caused by NSP3. This response seems to be triggered by more than one viral protein synthesized during the replication of the virus, but not by the viral double-stranded RNA (dsRNA), since cells transfected with psoralen-inactivated virions, or with naked viral dsRNA, did not induce UPR.",,"['Trujillo-Alonso, Vicenta', 'Maruri-Avidal, Liliana', 'Arias, Carlos F.', 'López, Susana']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.06490-11,PMC3209376,,,,,,,,,
,PMC,Avian Coronavirus in Wild Aquatic Birds,http://dx.doi.org/10.1128/JVI.05838-11,PMC3209365,,,"We detected a high prevalence (12.5%) of novel avian coronaviruses in aquatic wild birds. Phylogenetic analyses of these coronaviruses suggest that there is a diversity of gammacoronaviruses and deltacoronaviruses circulating in birds. Gammacoronaviruses were found predominantly in Anseriformes birds, whereas deltacoronaviruses could be detected in Ciconiiformes, Pelecaniformes, and Anseriformes birds in this study. We observed that there are frequent interspecies transmissions of gammacoronaviruses between duck species. In contrast, deltacoronaviruses may have more stringent host specificities. Our analysis of these avian viral and host mitochondrial DNA sequences also suggests that some, but not all, coronaviruses may have coevolved with birds from the same order.",,"['Chu, Daniel K. W.', 'Leung, Connie Y. H.', 'Gilbert, Martin', 'Joyner, Priscilla H.', 'Ng, Erica M.', 'Tse, Tsemay M.', 'Guan, Yi', 'Peiris, Joseph S. M.', 'Poon, Leo L. M.']",,,,
,PMC,A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge,http://dx.doi.org/10.1128/JVI.06048-11,PMC3209347,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) is an important emerging virus that is highly pathogenic in aged populations and is maintained with great diversity in zoonotic reservoirs. While a variety of vaccine platforms have shown efficacy in young-animal models and against homologous viral strains, vaccine efficacy has not been thoroughly evaluated using highly pathogenic variants that replicate the acute end stage lung disease phenotypes seen during the human epidemic. Using an adjuvanted and an unadjuvanted double-inactivated SARS-CoV (DIV) vaccine, we demonstrate an eosinophilic immunopathology in aged mice comparable to that seen in mice immunized with the SARS nucleocapsid protein, and poor protection against a nonlethal heterologous challenge. In young and 1-year-old animals, we demonstrate that adjuvanted DIV vaccine provides protection against lethal disease in young animals following homologous and heterologous challenge, although enhanced immune pathology and eosinophilia are evident following heterologous challenge. In the absence of alum, DIV vaccine performed poorly in young animals challenged with lethal homologous or heterologous strains. In contrast, DIV vaccines (both adjuvanted and unadjuvanted) performed poorly in aged-animal models. Importantly, aged animals displayed increased eosinophilic immune pathology in the lungs and were not protected against significant virus replication. These data raise significant concerns regarding DIV vaccine safety and highlight the need for additional studies of the molecular mechanisms governing DIV-induced eosinophilia and vaccine failure, especially in the more vulnerable aged-animal models of human disease.",,"['Bolles, Meagan', 'Deming, Damon', 'Long, Kristin', 'Agnihothram, Sudhakar', 'Whitmore, Alan', 'Ferris, Martin', 'Funkhouser, William', 'Gralinski, Lisa', 'Totura, Allison', 'Heise, Mark', 'Baric, Ralph S.']",,,,
,PMC,Viruses and Multiple Sclerosis,http://dx.doi.org/10.1177/1073858411386615,PMC3293404,,,"Multiple sclerosis (MS) is a chronic demyelinating disorder of unknown etiology, possibly caused by a virus or virus-triggered immunopathology. The virus might reactivate after years of latency and lyse oligodendrocytes, as in progressive multifocal leukoencephalopathy, or initiate immunopathological demyelination, as in animals infected with Theiler’s murine encephalomyelitis virus or coronaviruses. The argument for a viral cause of MS is supported by epidemiological analyses and studies of MS in identical twins, indicating that disease is acquired. However, the most important evidence is the presence of bands of oligoclonal IgG (OCBs) in MS brain and CSF that persist throughout the lifetime of the patient. OCBs are found almost exclusively in infectious CNS disorders, and antigenic targets of OCBs represent the agent that causes disease. Here, the authors review past attempts to identify an infectious agent in MS brain cells and discuss the promise of using recombinant antibodies generated from clonally expanded plasma cells in brain and CSF to identify disease-relevant antigens. They show how this strategy has been used successfully to analyze antigen specificity in subacute sclerosing panencephalitis, a chronic encephalitis caused by measles virus, and in neuromyelitis optica, a chronic autoimmune demyelinating disease produced by antibodies directed against the aquaporin-4 water channel.",,"['Owens, Gregory P.', 'Gilden, Don', 'Burgoon, Mark P.', 'Yu, Xiaoli', 'Bennett, Jeffrey L.']",,,,
,PMC,In This Issue,http://dx.doi.org/10.1002/pro.756,PMC3302638,,,,,,,,,
,PMC,ACBD3-mediated recruitment of PI4KB to picornavirus RNA replication sites,http://dx.doi.org/10.1038/emboj.2011.429,PMC3273392,,,"Phosphatidylinositol 4-kinase IIIβ (PI4KB) is a host factor required for genome RNA replication of enteroviruses, small non-enveloped viruses belonging to the family Picornaviridae. Here, we demonstrated that PI4KB is also essential for genome replication of another picornavirus, Aichi virus (AiV), but is recruited to the genome replication sites by a different strategy from that utilized by enteroviruses. AiV non-structural proteins, 2B, 2BC, 2C, 3A, and 3AB, interacted with a Golgi protein, acyl-coenzyme A binding domain containing 3 (ACBD3). Furthermore, we identified previously unknown interaction between ACBD3 and PI4KB, which provides a novel manner of Golgi recruitment of PI4KB. Knockdown of ACBD3 or PI4KB suppressed AiV RNA replication. The viral proteins, ACBD3, PI4KB, and phophatidylinositol-4-phosphate (PI4P) localized to the viral RNA replication sites. AiV replication and recruitment of PI4KB to the RNA replication sites were not affected by brefeldin A, in contrast to those in enterovirus infection. These results indicate that a viral protein/ACBD3/PI4KB complex is formed to synthesize PI4P at the AiV RNA replication sites and plays an essential role in viral RNA replication.",,"['Sasaki, Jun', 'Ishikawa, Kumiko', 'Arita, Minetaro', 'Taniguchi, Koki']",,,,
,PMC,Triterpene Functional Genomics in Licorice for Identification of CYP72A154 Involved in the Biosynthesis of Glycyrrhizin([C])([W])([OA]),http://dx.doi.org/10.1105/tpc.110.082685,PMC3246328,,,"Glycyrrhizin, a triterpenoid saponin derived from the underground parts of Glycyrrhiza plants (licorice), has several pharmacological activities and is also used worldwide as a natural sweetener. The biosynthesis of glycyrrhizin involves the initial cyclization of 2,3-oxidosqualene to the triterpene skeleton β-amyrin, followed by a series of oxidative reactions at positions C-11 and C-30, and glycosyl transfers to the C-3 hydroxyl group. We previously reported the identification of a cytochrome P450 monooxygenase (P450) gene encoding β-amyrin 11-oxidase (CYP88D6) as the initial P450 gene in glycyrrhizin biosynthesis. In this study, a second relevant P450 (CYP72A154) was identified and shown to be responsible for C-30 oxidation in the glycyrrhizin pathway. CYP72A154 expressed in an engineered yeast strain that endogenously produces 11-oxo-β-amyrin (a possible biosynthetic intermediate between β-amyrin and glycyrrhizin) catalyzed three sequential oxidation steps at C-30 of 11-oxo-β-amyrin supplied in situ to produce glycyrrhetinic acid, a glycyrrhizin aglycone. Furthermore, CYP72A63 of Medicago truncatula, which has high sequence similarity to CYP72A154, was able to catalyze C-30 oxidation of β-amyrin. These results reveal a function of CYP72A subfamily proteins as triterpene-oxidizing enzymes and provide a genetic tool for engineering the production of glycyrrhizin.",,"['Seki, Hikaru', 'Sawai, Satoru', 'Ohyama, Kiyoshi', 'Mizutani, Masaharu', 'Ohnishi, Toshiyuki', 'Sudo, Hiroshi', 'Fukushima, Ery Odette', 'Akashi, Tomoyoshi', 'Aoki, Toshio', 'Saito, Kazuki', 'Muranaka, Toshiya']",,,,
,PMC,X-ray structure of the arenavirus glycoprotein GP2 in its postfusion hairpin conformation,http://dx.doi.org/10.1073/pnas.1108910108,PMC3250147,,,"Arenaviruses are important agents of zoonotic disease worldwide. The virions expose a tripartite envelope glycoprotein complex at their surface, formed by the glycoprotein subunits GP1, GP2 and the stable signal peptide. This complex is responsible for binding to target cells and for the subsequent fusion of viral and host-cell membranes for entry. During this process, the acidic environment of the endosome triggers a fusogenic conformational change in the transmembrane GP2 subunit of the complex. We report here the crystal structure of the recombinant GP2 ectodomain of the lymphocytic choriomeningitis virus, the arenavirus type species, at 1.8-Å resolution. The structure shows the characteristic trimeric coiled coil present in class I viral fusion proteins, with a central stutter that allows a close structural alignment with most of the available structures of class I and III viral fusion proteins. The structure further shows a number of intrachain salt bridges stabilizing the postfusion hairpin conformation, one of which involves an aspartic acid that appears released from a critical interaction with the stable signal peptide upon low pH activation.",,"['Igonet, Sébastien', 'Vaney, Marie-Christine', 'Vonrhein, Clemens', 'Bricogne, Gérard', 'Stura, Enrico A.', 'Hengartner, Hans', 'Eschli, Bruno', 'Rey, Félix A.']",,,,
,PMC,"Type I interferons: diversity of sources, production pathways and effects on immune responses",http://dx.doi.org/10.1016/j.coviro.2011.10.026,PMC3572907,,,"Type I interferons (IFN-I) were first described over 50 years ago as factors produced by cells that interfere with virus replication and promote an antiviral state. Innate and adaptive immune responses to viruses are also greatly influenced by IFN-I. In this article we discuss the diversity of cellular sources of IFN-I and the pathways leading to IFN-I production during viral infections. Finally, we discuss the effects of IFN-I on cells of the immune system with emphasis on dendritic cells.",,"['Swiecki, Melissa', 'Colonna, Marco']",,,,
,PMC,A viral deubiquitylating enzyme targets viral RNA-dependent RNA polymerase and affects viral infectivity,http://dx.doi.org/10.1038/emboj.2011.424,PMC3273391,,,"Selective protein degradation via the ubiquitin-proteasome system (UPS) plays an essential role in many major cellular processes, including host–pathogen interactions. We previously reported that the tightly regulated viral RNA-dependent RNA polymerase (RdRp) of the positive-strand RNA virus Turnip yellow mosaic virus (TYMV) is degraded by the UPS in infected cells, a process that affects viral infectivity. Here, we show that the TYMV 98K replication protein can counteract this degradation process thanks to its proteinase domain. In-vitro assays revealed that the recombinant proteinase domain is a functional ovarian tumour (OTU)-like deubiquitylating enzyme (DUB), as is the 98K produced during viral infection. We also demonstrate that 98K mediates in-vivo deubiquitylation of TYMV RdRp protein—its binding partner within replication complexes—leading to its stabilization. Finally, we show that this DUB activity contributes to viral infectivity in plant cells. The identification of viral RdRp as a specific substrate of the viral DUB enzyme thus reveals the intricate interplay between ubiquitylation, deubiquitylation and the interaction between viral proteins in controlling levels of RdRp and viral infectivity.",,"['Chenon, Mélanie', 'Camborde, Laurent', 'Cheminant, Soizic', 'Jupin, Isabelle']",,,,
,PMC,Phosphorylation events during viral infections provide potential therapeutic targets,http://dx.doi.org/10.1002/rmv.722,PMC3334462,,,"For many medically relevant viruses, there is now considerable evidence that both viral and cellular kinases play important roles in viral infection. Ultimately, these kinases, and the cellular signaling pathways that they exploit, may serve as therapeutic targets for treating patients. Currently, small molecule inhibitors of kinases are under investigation as therapy for herpes viral infections. Additionally, a number of cellular or host-directed tyrosine kinase inhibitors that have been previously FDA-approved for cancer treatment are under study in animal models and clinical trials, as they have shown promise for the treatment of various viral infections as well. This review will highlight the wide range of viral proteins phosphorylated by viral and cellular kinases, and the potential for variability of kinase recognition sites within viral substrates to impact phosphorylation and kinase prediction. Research studying kinase-targeting prophylactic and therapeutic treatments for a number of viral infections will also be discussed.",,"['Keating, Julie A.', 'Striker, Rob']",,,,
,PMC,Local small airway epithelial injury induces global smooth muscle contraction and airway constriction,http://dx.doi.org/10.1152/japplphysiol.00739.2011,PMC3289432,,,"Small airway epithelial cells form a continuous sheet lining the conducting airways, which serves many functions including a physical barrier to protect the underlying tissue. In asthma, injury to epithelial cells can occur during bronchoconstriction, which may exacerbate airway hyperreactivity. To investigate the role of epithelial cell rupture in airway constriction, laser ablation was used to precisely rupture individual airway epithelial cells of small airways (<300-μm diameter) in rat lung slices (∼250-μm thick). Laser ablation of single epithelial cells using a femtosecond laser reproducibly induced airway contraction to ∼70% of the original cross-sectional area within several seconds, and the contraction lasted for up to 40 s. The airway constriction could be mimicked by mechanical rupture of a single epithelial cell using a sharp glass micropipette but not with a blunt glass pipette. These results suggest that soluble mediators released from the wounded epithelial cell induce global airway contraction. To confirm this hypothesis, the lysate of primary human small airway epithelial cells stimulated a similar airway contraction. Laser ablation of single epithelial cells triggered a single instantaneous Ca(2+) wave in the epithelium, and multiple Ca(2+) waves in smooth muscle cells, which were delayed by several seconds. Removal of extracellular Ca(2+) or decreasing intracellular Ca(2+) both blocked laser-induced airway contraction. We conclude that local epithelial cell rupture induces rapid and global airway constriction through release of soluble mediators and subsequent Ca(2+)-dependent smooth muscle shortening.",,"['Zhou, Jian', 'Alvarez-Elizondo, Martha B.', 'Botvinick, Elliot', 'George, Steven C.']",,,,
,PMC,Class II ADP-ribosylation Factors Are Required for Efficient Secretion of Dengue Viruses,http://dx.doi.org/10.1074/jbc.M111.270579,PMC3249131,,,"Identification and characterization of virus-host interactions are very important steps toward a better understanding of the molecular mechanisms responsible for disease progression and pathogenesis. To date, very few cellular factors involved in the life cycle of flaviviruses, which are important human pathogens, have been described. In this study, we demonstrate a crucial role for class II Arf proteins (Arf4 and Arf5) in the dengue flavivirus life cycle. We show that simultaneous depletion of Arf4 and Arf5 blocks recombinant subviral particle secretion for all four dengue serotypes. Immunostaining analysis suggests that class II Arf proteins are required at an early pre-Golgi step for dengue virus secretion. Using a horseradish peroxidase protein fused to a signal peptide, we show that class II Arfs act specifically on dengue virus secretion without altering the secretion of proteins through the constitutive secretory pathway. Co-immunoprecipitation data demonstrate that the dengue prM glycoprotein interacts with class II Arf proteins but not through its C-terminal VXPX motif. Finally, experiments performed with replication-competent dengue and yellow fever viruses demonstrate that the depletion of class II Arfs inhibits virus secretion, thus confirming their implication in the virus life cycle, although data obtained with West Nile virus pointed out the differences in virus-host interactions among flaviviruses. Our findings shed new light on a molecular mechanism used by dengue viruses during the late stages of the life cycle and demonstrate a novel function for class II Arf proteins.",,"['Kudelko, Mateusz', 'Brault, Jean-Baptiste', 'Kwok, Kevin', 'Li, Ming Yuan', 'Pardigon, Nathalie', 'Peiris, J. S. Malik', 'Bruzzone, Roberto', 'Desprès, Philippe', 'Nal, Béatrice', 'Wang, Pei Gang']",,,,
,PMC,Slowing down with age: lung DCs do it too,http://dx.doi.org/10.1172/JCI61367,PMC3226069,,,"Decline in immune function with age has been attributed to defects or alterations in both the innate and the adaptive immune system. In this issue of the JCI, Zhao and coworkers provide evidence for a novel mechanism of immune dysfunction in aging mice. They show that migration of respiratory DCs from the site of virus replication to the draining lymph nodes in response to infection with several different respiratory viruses is markedly diminished with increasing age. The impaired DC migration was a result of increased levels of the lipid mediator prostaglandin D(2) (PGD(2)) in the respiratory tract with age and could be partially reversed by blockade of PGD(2) synthesis or action.",,"['Braciale, Thomas J.', 'Kim, Taeg S.']",,,,
,PMC,"Age-related increases in PGD(2) expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice",http://dx.doi.org/10.1172/JCI59777,PMC3226008,,,"The morbidity and mortality associated with respiratory virus infection is felt most keenly among the elderly. T cells are necessary for viral clearance, and many age-dependent intrinsic T cell defects have been documented. However, the development of robust T cell responses in the lung also requires respiratory DCs (rDCs), which must process antigen and migrate to draining LNs (DLNs), and little is known about age-related defects in these T cell–extrinsic functions. Here, we show that increases in prostaglandin D(2) (PGD(2)) expression in mouse lungs upon aging correlate with a progressive impairment in rDC migration to DLNs. Decreased rDC migration resulted in diminished T cell responses and more severe clinical disease in older mice infected with respiratory viruses. Diminished rDC migration associated with virus-specific defects in T cell responses and was not a result of cell-intrinsic defect, rather it reflected the observed age-dependent increases in PGD(2) expression. Blocking PGD(2) function with small-molecule antagonists enhanced rDC migration, T cell responses, and survival. This effect correlated with upregulation on rDCs of CCR7, a chemokine receptor involved in DC chemotaxis. Our results suggest that inhibiting PGD(2) function may be a useful approach to enhance T cell responses against respiratory viruses in older humans.",,"['Zhao, Jincun', 'Zhao, Jingxian', 'Legge, Kevin', 'Perlman, Stanley']",,,,
,PMC,Long-Term Balancing Selection at the Antiviral Gene OAS1 in Central African Chimpanzees,http://dx.doi.org/10.1093/molbev/msr247,PMC3341824,,,"Oligoadenylate synthetases (OAS) are interferon-induced enzymes that participate in the first line of defense against a wide range of viral infection in animals. Upon activation by viral double-stranded RNA, OAS synthesizes (2–5) oligoadenylates, which activate RNase L, leading to the nonspecific degradation of cellular and viral RNA. Some association studies in humans suggest that variation at one of the OAS genes, OAS1, could be influencing host susceptibility to viral infection. We assessed the diversity of OAS1 in hominoid primates with a focus on chimpanzees. We found that the OAS1 gene is extremely polymorphic in Central African chimpanzee and exhibits levels of silent and replacement diversity much higher than neutral regions of the chimpanzee genome. This level of variation strongly suggests that balancing selection is acting on OAS1, and indeed, this conclusion was validated by several tests of neutrality. We further demonstrated that balancing selection has been acting at this locus since the split between chimpanzees, humans, and gorillas (∼8.6 Ma) and caused the persistence of two deeply divergent allelic lineages in Central African chimpanzees. These two groups of OAS1 alleles differ by a large number of amino acids (a.a.), including several a.a. putatively involved in RNA binding. It is therefore very likely that variation at the OAS1 locus affects the innate immune response of individuals to specific viral infection. Our data strongly suggest that interactions between viral RNA and OAS1 are responsible for the maintenance of ancestral polymorphisms at this locus for at least 13.2 My.",,"['Ferguson, William', 'Dvora, Shira', 'Fikes, Ronald W.', 'Stone, Anne C.', 'Boissinot, Stéphane']",,,,
,PMC,Epidemiology and Potential Preventative Measures for Viral Infections in Children With Malignancy and Those Undergoing Hematopoietic Cell Transplantation,http://dx.doi.org/10.1002/pbc.23417,PMC4008326,,,"In pediatric patients with malignancy and those receiving hematopoietic stem cell transplants, bacterial and fungal infections have been the focus of fever and neutropenia episodes for decades. However, improved diagnostic capabilities have revealed viral pathogens as a significant cause of morbidity and mortality. Because of limited effective antiviral therapies, prevention of viral infections is paramount. Pre-exposure and post-exposure prophylaxis and antiviral suppressive therapeutic approaches are reviewed. Additionally, infection control practices specific to this patient population are discussed. A comprehensive approach utilizing each of these can be effective at reducing the negative impact of viral infections.",,"['Fisher, Brian T.', 'Alexander, Sarah', 'Dvorak, Christopher C.', 'Zaoutis, Theoklis E.', 'Zerr, Danielle M.', 'Sung, Lillian']",,,,
,PMC,Temporally structured metapopulation dynamics and persistence of influenza A H3N2 virus in humans,http://dx.doi.org/10.1073/pnas.1109314108,PMC3228450,,,"Populations of seasonal influenza virus experience strong annual bottlenecks that pose a considerable extinction risk. It has been suggested that an influenza source population located in tropical Southeast or East Asia seeds annual temperate epidemics. Here we investigate the seasonal dynamics and migration patterns of influenza A H3N2 virus by analysis of virus samples obtained from 2003 to 2006 from Australia, Europe, Japan, New York, New Zealand, Southeast Asia, and newly sequenced viruses from Hong Kong. In contrast to annual temperate epidemics, relatively low levels of relative genetic diversity and no seasonal fluctuations characterized virus populations in tropical Southeast Asia and Hong Kong. Bayesian phylogeographic analysis using discrete temporal and spatial characters reveal high rates of viral migration between urban centers tested. Although the virus population that migrated between Southeast Asia and Hong Kong persisted through time, this was dependent on virus input from temperate regions and these tropical regions did not maintain a source for annual H3N2 influenza epidemics. We further show that multiple lineages may seed annual influenza epidemics, and that each region may function as a potential source population. We therefore propose that the global persistence of H3N2 influenza A virus is the result of a migrating metapopulation in which multiple different localities may seed seasonal epidemics in temperate regions in a given year. Such complex global migration dynamics may confound control efforts and contribute to the emergence and spread of antigenic variants and drug-resistant viruses.",,"['Bahl, Justin', 'Nelson, Martha I.', 'Chan, Kwok H.', 'Chen, Rubing', 'Vijaykrishna, Dhanasekaran', 'Halpin, Rebecca A.', 'Stockwell, Timothy B.', 'Lin, Xudong', 'Wentworth, David E.', 'Ghedin, Elodie', 'Guan, Yi', 'Peiris, J. S. Malik', 'Riley, Steven', 'Rambaut, Andrew', 'Holmes, Edward C.', 'Smith, Gavin J. D.']",,,,
,PMC,Mannose-Binding Lectin Contributes to Deleterious Inflammatory Response in Pandemic H1N1 and Avian H9N2 Infection,http://dx.doi.org/10.1093/infdis/jir691,PMC3242741,,,"Background. Mannose-binding lectin (MBL) is a pattern-recognition molecule, which functions as a first line of host defense. Pandemic H1N1 (pdmH1N1) influenza A virus caused massive infection in 2009 and currently circulates worldwide. Avian influenza A H9N2 (H9N2/G1) virus has infected humans and has the potential to be the next pandemic virus. Antiviral function and immunomodulatory role of MBL in pdmH1N1 and H9N2/G1 virus infection have not been investigated. Methods. In this study, MBL wild-type (WT) and MBL knockout (KO) murine models were used to examine the role of MBL in pdmH1N1 and H9N2/G1 virus infection. Results. Our study demonstrated that in vitro, MBL binds to pdmH1N1 and H9N2/G1 viruses, likely via the carbohydrate recognition domain of MBL. Wild-type mice developed more severe disease, as evidenced by a greater weight loss than MBL KO mice during influenza virus infection. Furthermore, MBL WT mice had enhanced production of proinflammatory cytokines and chemokines compared with MBL KO mice, suggesting that MBL could upregulate inflammatory responses that may potentially worsen pdmH1N1 and H9N2/G1 virus infections. Conclusions. Our study provided the first in vivo evidence that MBL may be a risk factor during pdmH1N1 and H9N2/G1 infection by upregulating proinflammatory response.",,"['Ling, Man To', 'Tu, Wenwei', 'Han, Yan', 'Mao, Huawei', 'Chong, Wai Po', 'Guan, Jing', 'Liu, Ming', 'Lam, Kwok Tai', 'Law, Helen K. W.', 'Peiris, J. S. Malik', 'Takahashi, K.', 'Lau, Yu Lung']",,,,
,PMC,Prior Infections With Seasonal Influenza A/H1N1 Virus Reduced the Illness Severity and Epidemic Intensity of Pandemic H1N1 Influenza in Healthy Adults,http://dx.doi.org/10.1093/cid/cir809,PMC3258274,,,"Background. A new influenza A/H1N1 (pH1N1) virus emerged in April 2009, proceeded to spread worldwide, and was designated as an influenza pandemic. A/H1N1 viruses had circulated in 1918–1957 and 1977–2009 and were in the annual vaccine during 1977–2009. Methods. Serum antibody to the pH1N1 and seasonal A/H1N1 viruses was measured in 579 healthy adults at enrollment (fall 2009) and after surveillance for illness (spring 2010). Subjects reporting with moderate to severe acute respiratory illness had illness and virus quantitation for 1 week; evaluations for missed illnesses were conducted over holiday periods and at the spring 2010 visit. Results. After excluding 66 subjects who received pH1N1 vaccine, 513 remained. Seventy-seven had reported with moderate to severe illnesses; 31 were infected with pH1N1 virus, and 30 with a rhinovirus. Determining etiology from clinical findings was not possible, but fever and prominent myalgias favored influenza and prominent rhinorrhea favored rhinovirus. Tests of fall and spring antibody indicated pH1N1 infection of 23% had occurred, with the rate decreasing with increasing anti-pH1N1 antibody; a similar pattern was seen for influenza-associated illness. A reducing frequency of pH1N1 infections was also seen with increasing antibody to the recent seasonal A/H1N1 virus (A/Brisbane/59/07). Preexisting antibody to pH1N1 virus, responses to a single vaccine dose, a low infection-to-illness ratio, and a short duration of illness and virus shedding among those with influenza indicated presence of considerable preexisting immunity to pH1N1 in the population. Conclusions. The 2009 A/H1N1 epidemic among healthy adults was relatively mild, most likely because of immunity from prior infections with A/H1N1 viruses.",,"['Couch, Robert B.', 'Atmar, Robert L.', 'Franco, Luis M.', 'Quarles, John M.', 'Niño, Diane', 'Wells, Janet M.', 'Arden, Nancy', 'Cheung, Sheree', 'Belmont, John W.']",,,,
,PMC,Antiviral Activity of Natural Products Extracted from Marine Organisms,http://dx.doi.org/10.5681/bi.2011.029,PMC3648973,,,"Many epidemics have broken out over the centuries. Hundreds and thousands of humans have died over a disease. Available treatments for infectious diseases have always been limited. Some infections are more deadly than the others, especially viral pathogens. These pathogens have continuously resisted all kinds of medical treatment, due to a need for new treatments to be developed. Drugs are present in nature and are also synthesized in vitro and they help in combating diseases and restoring health. Synthesizing drugs is a hard and time consuming task, which requires a lot of man power and financial aid. However, the natural compounds are just lying around on the earth, may it be land or water. Over a thousand novel compounds isolated from marine organisms are used as antiviral agents. Others are being pharmacologically tested. Today, over forty antiviral compounds are present in the pharmacological market. Some of these compounds are undergoing clinical and preclinical stages. Marine compounds are paving the way for a new trend in modern medicine.",,"['Uzair, Bushra', 'Mahmood, Zahra', 'Tabassum, Sobia']",,,,
,PMC,Estimating the transmission potential of supercritical processes based on the final size distribution of minor outbreaks,http://dx.doi.org/10.1016/j.jtbi.2011.10.039,PMC3249525,,,"Use of the final size distribution of minor outbreaks for the estimation of the reproduction numbers of supercritical epidemic processes has yet to be considered. We used a branching process model to derive the final size distribution of minor outbreaks, assuming a reproduction number above unity, and applying the method to final size data for pneumonic plague. Pneumonic plague is a rare disease with only one documented major epidemic in a spatially limited setting. Because the final size distribution of a minor outbreak needs to be normalized by the probability of extinction, we assume that the dispersion parameter (k) of the negative-binomial offspring distribution is known, and examine the sensitivity of the reproduction number to variation in dispersion. Assuming a geometric offspring distribution with k = 1, the reproduction number was estimated at 1.16 (95% confidence interval: 0.97–1.38). When less dispersed with k = 2, the maximum likelihood estimate of the reproduction number was 1.14. These estimates agreed with those published from transmission network analysis, indicating that the human-to-human transmission potential of the pneumonic plague is not very high. Given only minor outbreaks, transmission potential is not sufficiently assessed by directly counting the number of offspring. Since the absence of a major epidemic does not guarantee a subcritical process, the proposed method allows us to conservatively regard epidemic data from minor outbreaks as supercritical, and yield estimates of threshold values above unity.",,"['Nishiura, Hiroshi', 'Yan, Ping', 'Sleeman, Candace K.', 'Mode, Charles J.']",,,,
,PMC,The Search for Meaning in Virus Discovery,http://dx.doi.org/10.1016/j.coviro.2011.10.010,PMC4310690,,,,,"['Ipkin, Ian', 'Daszak, Peter']",,,,
,PMC,VP-1 Quasispecies in Human Infection with Polyomavirus BK,http://dx.doi.org/10.1002/jmv.22147,PMC3220780,,,"Polyomavirus BK is a recognized cause of nephropathy and hemorrhagic cystitis in kidney or allogeneic hematopoietic stem cell transplant recipients. This study explored a role of genetic variations in capsid protein VP-1 gene as a factor in viral pathogenesis. VP-1 was amplified from 7 healthy subjects with viruria, 7 transplant patients with viruria, and 11 patients with viremia or nephropathy. PCR products were cloned and a total of 558 clonal sequences were subjected to phylogenetic analysis using standard methods. VP-1 quasispecies were found in 25/25 and coinfection with different genotypes in 12/ 25 subjects. Genotype II was found as an unexpected minority species in 5/25 individuals. Recombinant strains of uncertain biologic significance, which frequently contained genotype II and IV sequences were identified in 9/25 subjects. Viremia/nephropathy group was characterized by (a) greater sequence complexity in whole VP-1 versus BC loop and BC loop compared to the HI loop, (b) greater intra-strain genetic diversity in the BC loop compared to whole VP-1 protein and HI loop, (c) more non-synonymous substitutions (dN) in the BC loop compared to whole VP-1 and HI loop, (e) fewer synonymous substitutions (dS) compared to healthy-viruria group, and (f) selection pressure (dN/dS >1.0) exerted on VP-1. In conclusion, this study documents frequent occurrence of quasispecies in a host DNA polymerase dependent virus which is theoretically expected to show high replication fidelity. Quasispecies occur even in healthy subjects with viruria, but evolutionary selection pressure directed at the viral capsid protein VP-1 is seen only in patients with viremia.",,"['Luo, Chunqing', 'Hirsch, Hans', 'Kant, Jeffrey', 'Randhawa, Parmjeet']",,,,
,PMC,Development of a hyena immunology toolbox,http://dx.doi.org/10.1016/j.vetimm.2011.10.016,PMC3273618,,,"Animals that hunt and scavenge are often exposed to a broad array of pathogens. Theory predicts the immune systems of animals specialized for scavenging should have been molded by selective pressures associated with surviving microbial assaults from their food. Spotted hyenas (Crocuta crocuta) are capable hunters that have recently descended from carrion feeding ancestors. Hyenas have been documented to survive anthrax and rabies infections, and outbreaks of several other viral diseases that decimated populations of sympatric carnivores. In light of the extreme disease resistance manifested by spotted hyenas, our objective was to identify tools available for studying immune function in spotted hyenas and use these tools to document the hyena antibody response to immunization. Domestic cats (Felis catus) are the closest phylogenetic relatives of hyenas that have been studied in detail immunologically, and we hypothesized that anti-cat isotype-specific antibodies would cross react with hyena immunoglobulin epitopes. We used ELISA and Western blots to test isotype-specific anti-feline antibodies for specific cross-reaction to hyena Ig epitopes. Molecular weights of heavy (IgA, IgG, IgM) and light chains of hyena immunoglobulins were determined by protein electrophoresis, and as expected, they were found to be similar to feline immunoglobulins. In order to further validate the cross-reactivity of the anti-feline antibodies and document the hyena humoral response, eight spotted hyenas were immunized with dinitrophenol conjugated keyhole limpet hemocyanin (DNP-KLH) and serum anti-DNP responses were monitored by enzyme-linked immunosorbent assay (ELISA) for one year. The full array of isotype-specific antibodies identified here will allow veterinarians and other researchers to thoroughly investigate the hyena antibody response, and can be used in future studies to test hypotheses about pathogen exposure and immune function in this species.",,"['Flies, Andrew S.', 'Grant, Chris K.', 'Mansfield, Linda S.', 'Tsao, Jean', 'Smith, Eric J.', 'Weldele, Mary L.', 'Holekamp, Kay E.']",,,,
,PMC,Future Infectious Disease Threats to Europe,http://dx.doi.org/10.2105/AJPH.2011.300181,PMC3222407,,,"We examined how different drivers of infectious disease could interact to threaten control efforts in Europe. We considered projected trends through 2020 for 3 broad groups of drivers: globalization and environmental change, social and demographic change, and health system capacity. Eight plausible infectious disease threats with the potential to be significantly more problematic than they are today were identified through an expert consultation: extensively drug-resistant bacteria, vector-borne diseases, sexually transmitted infections, food-borne infections, a resurgence of vaccine-preventable diseases, health care–associated infections, multidrug-resistant tuberculosis, and pandemic influenza. Preemptive measures to be taken by the public health community to counteract these threats were identified.",,"['Suk, Jonathan E.', 'Semenza, Jan C.']",,,,
,PMC,Lower Airway Rhinovirus Burden and the Seasonal Risk of Asthma Exacerbation,http://dx.doi.org/10.1164/rccm.201103-0585OC,PMC3208645,,,"Rationale: Most asthma exacerbations are initiated by viral upper respiratory illnesses. It is unclear whether human rhinovirus (HRV)–induced exacerbations are associated with greater viral replication and neutrophilic inflammation compared with HRV colds. Objectives: To evaluate viral strain and load in a prospective asthma cohort during a natural cold. Methods: Adults were enrolled at the first sign of a cold, with daily monitoring of symptoms, medication use, and peak expiratory flow rate until resolution. Serial nasal lavage and induced sputum samples were assessed for viral copy number and inflammatory cell counts. Measurements and Main Results: A total of 52 persons with asthma and 14 control subjects without atopy or asthma were studied for over 10 weeks per subject on average; 25 participants developed an asthma exacerbation. Detection of HRVs in the preceding 5 days was the most common attributable exposure related to exacerbation. Compared with other infections, those by a minor group A HRV were 4.4-fold more likely to cause exacerbation (P = 0.038). Overall, sputum neutrophils and the burden of rhinovirus in the lower airway were similar in control subjects without atopy and the asthma group. However, among HRV-infected participants with asthma, exacerbations were associated with greater sputum neutrophil counts (P = 0.005). Conclusions: HRV infection is a frequent cause of exacerbations in adults with asthma and a cold, and there may be group-specific differences in severity of these events. The absence of large differences in viral burden among groups suggests differential lower airway sensitization to the effects of neutrophilic inflammation in the patients having exacerbations.",,"['Denlinger, Loren C.', 'Sorkness, Ron L.', 'Lee, Wai-Ming', 'Evans, Michael D.', 'Wolff, Michele J.', 'Mathur, Sameer K.', 'Crisafi, Gina M.', 'Gaworski, Katie L.', 'Pappas, Tressa E.', 'Vrtis, Rose F.', 'Kelly, Elizabeth A.', 'Gern, James E.', 'Jarjour, Nizar N.']",,,,
,PMC,Griffithsin Has Antiviral Activity against Hepatitis C Virus,http://dx.doi.org/10.1128/AAC.00633-11,PMC3194994,,,"Hepatitis C virus (HCV)-infected patients undergoing liver transplantation universally experience rapid reinfection of their new liver graft. Current treatment protocols do not prevent graft reinfection and, in addition, an accelerated disease progression is observed. In the present study, we have evaluated a novel strategy to prevent HCV infection using a lectin, griffithsin (GRFT) that specifically binds N-linked high-mannose oligosaccharides that are present on the viral envelope. The antiviral effect of GRFT was evaluated in vitro using the HCV pseudoparticle (HCVpp) and HCV cell culture (HCVcc) systems. We show here that preincubation of HCVpp and HCVcc with GRFT prevents infection of Huh-7 hepatoma cells. Furthermore, GRFT interferes with direct cell-to-cell transmission of HCV. GRFT acts at an early phase of the viral life cycle by interfering in a genotype-independent fashion with the interaction between the viral envelope proteins and the viral receptor CD81. The capacity of GRFT to prevent infection in vivo was evaluated using uPA(+/+)-SCID mice (uPA stands for urokinase-type plasminogen activator) that harbor human primary hepatocytes in their liver (chimeric mice). In this proof-of-concept trial, we demonstrated that GRFT can mitigate HCV infection of chimeric mice. Treated animals that did become infected demonstrated a considerable delay in the kinetics of the viral infection. Our data demonstrate that GRFT can prevent HCV infection in vitro and mitigate HCV infection in vivo. GRFT treatment of chronically infected HCV patients undergoing liver transplantation may be a suitable strategy to prevent infection of the liver allograft.",,"['Meuleman, Philip', 'Albecka, Anna', 'Belouzard, Sandrine', 'Vercauteren, Koen', 'Verhoye, Lieven', 'Wychowski, Czeslaw', 'Leroux-Roels, Geert', 'Palmer, Kenneth E.', 'Dubuisson, Jean']",,,,
,PMC,Coronavirus nsp6 proteins generate autophagosomes from the endoplasmic reticulum via an omegasome intermediate,http://dx.doi.org/10.4161/auto.7.11.16642,PMC3242798,,,"Autophagy is a cellular response to starvation which generates autophagosomes to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy can provide an innate defense against virus infection, or conversely autophagosomes can promote infection by facilitating assembly of replicase proteins. We demonstrate that the avian coronavirus, infectious bronchitis virus (IBV), activates autophagy. A screen of individual IBV nonstructural proteins (nsps) showed that autophagy was activated by IBV nsp6. This property was shared with nsp6 of mammalian coronaviruses mouse hepatitis virus, and severe acute respiratory syndrome virus, and the equivalent nsp5–7 of the arterivirus porcine reproductive and respiratory syndrome virus. These multiple-spanning transmembrane proteins located to the endoplasmic reticulum (ER) where they generated Atg5 and LC3II -positive vesicles, and vesicle formation was dependent on Atg5 and class III PI3 kinase. The vesicles recruited double-FYVE-domain containing protein (DFCP) indicating localized concentration of phosphatidylinositol 3 phosphate, and therefore shared many features with omegasomes formed from the ER in response to starvation. Omegasomes induced by viral nsp6 matured into autophagosomes that delivered LC3 to lysosomes and therefore recruited and recycled the proteins needed for autophagosome nucleation, expansion, cellular trafficking and delivery of cargo to lysosomes. The coronavirus nsp6 proteins activated omegasome and autophagosome formation independently of starvation, but activation did not involve direct inhibition of mTOR signaling, activation of sirtuin 1 or induction of ER stress.",,"['Cottam, Eleanor M', 'Maier, Helena J', 'Manifava, Maria', 'Vaux, Laura C', 'Chandra-Schoenfelder, Priya', 'Gerner, Wilhelm', 'Britton, Paul', 'Ktistakis, Nick T', 'Wileman, Tom']",,,,
,PMC,High Incidence of Severe Influenza among Individuals over 50 Years of Age,http://dx.doi.org/10.1128/CVI.05357-11,PMC3209033,,,"Age-specific epidemiological data on asymptomatic, symptomatic, and severe infections are essential for public health policies on combating influenza. In this study, we incorporated data on microbiologically confirmed infections and seroprevalence to comprehensively describe the epidemiology of pandemic H1N1 2009 influenza. Seroprevalence was determined from 1,795 random serum samples collected in our hospital in January 2007 (before the first wave of the pandemic) and March 2010 (after the second wave). Data on microbiologically confirmed infection and severe cases were obtained from the Centre for Health Protection in Hong Kong. Severe cases were most common in the 51- to 60-year-old age group. The microbiologically confirmed incidence rate was highest for children aged ≤10 years and dropped sharply for the adult population (ρ = −1.0; P < 0.01), but the incidence rate for severe disease was highest for the 51- to 60-year-old age group. For the 51- to 60-year-old age group, the seroprevalence was similar to that for the younger age groups, but the proportion of severe cases relative to seroprevalence was significantly higher than that for 11- to 50-year-old age groups. As judged from the percentage of specimens positive for other respiratory viruses compared with that for pandemic H1N1 virus, the impact of symptomatic disease due to pandemic H1N1 virus was higher than that for other respiratory viruses in people aged ≤50 years. In conclusion, the 51- to 60-year-old age group, which had the highest overall incidence and the highest rate of severe disease but is currently not considered by the World Health Organization to be an at-risk group, should be prioritized for influenza vaccination in areas where universal influenza vaccination is not practiced.",,"['Zhang, Anna J. X.', 'To, Kelvin K. W.', 'Tse, Herman', 'Chan, Kwok-Hung', 'Guo, Kun-Yuan', 'Li, Can', 'Hung, Ivan F. N.', 'Chan, Jasper F. W.', 'Chen, Honglin', 'Tam, Sidney', 'Yuen, Kwok-Yung']",,,,
,PMC,Enhanced Effect of DNA Immunization plus In Vivo Electroporation with a Combination of Hepatitis B Virus Core-PreS1 and S-PreS1 Plasmids,http://dx.doi.org/10.1128/CVI.05113-11,PMC3209024,,,"To develop a novel, effective HBV therapeutic vaccine, we constructed two HBV DNA immunogens that contained PreS1, HBSS1, and HBCS1. Several delivery methods, such as intramuscular (i.m.) injection, intramuscular injection plus electroporation (i.m.-EP), and intradermal injection plus electroporation (i.d.-EP) were used in a murine model to analyze and compare the immune responses that were induced by the DNA immunogens. We found that i.d.-EP accelerated specific antibody seroconversion and produced high antibody (anti-PreS1, anti-S, and anti-C antibody) titers after HBSS1 and HBCS1 immunization. Combining the HBSS1 and HBCS1 DNA immunogens with i.d.-EP produced the strongest multiantigen (PreS1, S, and C)-specific cellular immune response and the highest specific PreS1 antibody levels. The results indicated that DNA immunization using HBSS1 and HBCS1 might be an ideal candidate, with its ability to elicit robust B and T cell immune responses against multiantigen when combined with optimized delivery technology. The present study provides a basis for the design and rational application of a novel HBV DNA vaccine.",,"['Chen, Hong', 'Wen, Bo', 'Deng, Yao', 'Wang, Wen', 'Yin, Xiao', 'Guan, Jie', 'Ruan, Li', 'Tan, Wenjie']",,,,
,PMC,Development of a Poliovirus Neutralization Test with Poliovirus Pseudovirus for Measurement of Neutralizing Antibody Titer in Human Serum,http://dx.doi.org/10.1128/CVI.05225-11,PMC3209023,,,"In the Global Polio Eradication Initiative, laboratory diagnosis plays a critical role by isolating and identifying poliovirus (PV) from the stool samples from acute flaccid paralysis (AFP) cases. In recent years, reestablishment of PV circulation in countries where PV was previously eliminated has occurred because of decreased herd immunity, possibly due to poor vaccination coverage. To monitor the vulnerability of countries to PV circulation, surveillance of neutralizing-antibody titers against PV in susceptible populations is essential in the end game of the polio eradication program. In this study, we have developed a PV neutralization test with type 1, 2, and 3 PV pseudoviruses to determine the neutralizing-antibody titer against PV in human serum samples. With this test, the neutralizing-antibody titer against PV could be determined within 2 days by automated interpretation of luciferase signals without using infectious PV strains. We validated the pseudovirus PV neutralization test with 131 human serum samples collected from a wide range of age groups (ages 1 to >60 years) by comparison with a conventional neutralization test. We found good correlation in the neutralizing-antibody titers determined by these tests. These results suggest that a pseudovirus PV neutralization test would serve as a safe and simple procedure for the measurement of the neutralizing-antibody titer against PV.",,"['Arita, Minetaro', 'Iwai, Masae', 'Wakita, Takaji', 'Shimizu, Hiroyuki']",,,,
,PMC,Immunization of Mice with Lactobacillus casei Expressing a Beta-Intimin Fragment Reduces Intestinal Colonization by Citrobacter rodentium,http://dx.doi.org/10.1128/CVI.05262-11,PMC3209022,,,"Enteropathogenic Escherichia coli (EPEC) is a common cause of diarrhea in children from developing countries. Intimate adhesion of the bacteria to intestinal cells occurs via binding of the adhesin intimin to the TIR receptor exposed on cell surfaces. Here, Lactobacillus casei expressing a fragment of β-intimin (L. casei-Int(cv)) was tested as mucosal vaccines in mice against intestinal colonization with the murine pathogen Citrobacter rodentium. Oral or sublingual immunization of C57BL/6 mice with L. casei-Int(cv) induced anti-Int(cv) IgA in feces but no IgG in sera. Conversely, anti-Int(cv) IgG was induced in the sera of mice after sublingual immunization with purified Int(cv). All vaccines were able to decrease C. rodentium recovery from feces. However, this reduction was more evident and sustained over time in mice immunized with L. casei-Int(cv) by the sublingual route. These mice also displayed an increase in interleukin 6 (IL-6) and gamma interferon (IFN-γ) secretion by spleen cells 10 days after infection. Additionally, oral or sublingual immunization of C3H/HePas mice, which are highly susceptible to C. rodentium infection, with L. casei-Int(cv) induced anti-Int(cv) antibodies and significantly increased survival after challenge. Immunohistological analysis of colon sections revealed that C. rodentium was located in deep fractions of the tissue from C3H/HePas mice immunized with L. casei whereas superficial staining was observed in colon sections from mice immunized with L. casei-Int(cv.) The results indicate that vaccines composed of L. casei expressing intimin may represent a promising approach and that the C3H/HePas infection model with C. rodentium can be used to evaluate potential vaccines against EPEC.",,"['Ferreira, P. C. D.', 'da Silva, J. B.', 'Piazza, R. M. F.', 'Eckmann, L.', 'Ho, P. L.', 'Oliveira, M. L. S.']",,,,
,PMC,Immunogenicity of Recombinant Classic Swine Fever Virus CD8(+) T Lymphocyte Epitope and Porcine Parvovirus VP2 Antigen Coexpressed by Lactobacillus casei in Swine via Oral Vaccination,http://dx.doi.org/10.1128/CVI.05204-11,PMC3209017,,,"Classical swine fever virus (CSFV) and porcine parvovirus (PPV) are highly contagious pathogens, resulting in enormous economic losses in pig industries worldwide. Because vaccines play an important role in disease control, researchers are seeking improved vaccines that could induce antiviral immune responses against CSFV and PPV at the mucosal and systemic levels simultaneously. In this study, a genetically engineered Lactobacillus strain coexpressing the CSFV-specific cytotoxic T lymphocyte (CTL) epitope 290 and the VP2 antigen of PPV was developed, and its immunopotentiating capacity as an oral vaccine in pigs was analyzed. The data demonstrated that in the absence of any adjuvant, the recombinant Lactobacillus strain can efficiently stimulate mucosal and systemic CSFV-specific CD8(+) CTL responses to protect pigs against CSFV challenge. Moreover, anti-PPV-VP2 serum IgG and mucosal IgA were induced in pigs immunized orally with the recombinant Lactobacillus strain, showing a neutralizing effect on PPV infection. The results suggest that the recombinant Lactobacillus microecological agent may be a valuable component of a strategy for development of a vaccine against CSFV and PPV.",,"['Xu, Yigang', 'Cui, Lichun', 'Tian, Changyong', 'Zhang, Guocai', 'Huo, Guicheng', 'Tang, Lijie', 'Li, Yijing']",,,,
,PMC,Assessment of Lactobacillus gasseri as a Candidate Oral Vaccine Vector,http://dx.doi.org/10.1128/CVI.05277-11,PMC3209016,,,"Lactobacillus species are commensal bacteria that have long been recognized as probiotic microbes and are generally regarded as safe (GRAS) for human consumption. We have investigated the use of L. gasseri as a vaccine vector for oral immunization against mucosal pathogens. Recent research has shown that the immune response to different lactobacilli can vary widely depending on the species or subspecies of Lactobacillus being studied. While some lactobacilli seem to induce oral tolerance, others induce an adaptive immune response. This study characterized the systemic and mucosal immune response to wild-type and genetically modified L. gasseri. L. gasseri primarily activates TLR2/6, with additional activation through the TLR2 homodimer. To expand the Toll-like receptor (TLR) activation profile of L. gasseri and the immunogenicity of the vector, a plasmid containing fliC, the gene encoding bacterial flagellin, was introduced which resulted in the strong activation of TLR5. The treatment of human myeloid dendritic cells with recombinant lactobacilli expressing flagellin triggered phenotypic maturation and the release of proinflammatory cytokines. In contrast, bacterial treatment also resulted in a statistically significant increase in IL-10 production. In vivo studies established that treatment with L. gasseri led to a diversification of B-cell populations in the lamina propria of the murine colon. Furthermore, treatment with genetically modified L. gasseri led to a significant decrease in the percentage of FoxP3(+) colonic lymphocytes. Taken together, these data clarify the interaction of L. gasseri with the host immune system and support further investigation of the in vivo immunogenicity of L. gasseri expressing both flagellin and candidate vaccine antigens.",,"['Stoeker, Laura', 'Nordone, Shila', 'Gunderson, Sara', 'Zhang, Lin', 'Kajikawa, Akinobu', 'LaVoy, Alora', 'Miller, Michael', 'Klaenhammer, Todd R.', 'Dean, Gregg A.']",,,,
,PMC,Animal virus schemes for translation dominance,http://dx.doi.org/10.1016/j.coviro.2011.10.009,PMC3272495,,,"Viruses have adapted a broad range of unique mechanisms to modulate the cellular translational machinery to ensure viral translation at the expense of cellular protein synthesis. Many of these promote virus-specific translation by use of molecular tags on viral mRNA such as internal ribosome entry sites (IRES) and genome-linked viral proteins (VPg) that bind translation machinery components in unusual ways and promote RNA circularization. This review describes recent advances in understanding some of the mechanisms in which animal virus mRNAs gain an advantage over cellular transcripts, including new structural and biochemical insights into IRES function and novel proteins that function as alternate met-tRNA(i)(met) carriers in translation initiation. Comparisons between animal and plant virus mechanisms that promote translation of viral mRNAs are discussed.",,"['Reineke, Lucas C.', 'Lloyd, Richard E.']",,,,
,PMC,Rapid Mapping and Identification of Mutations in Caenorhabditis elegans by Restriction Site-Associated DNA Mapping and Genomic Interval Pull-Down Sequencing,http://dx.doi.org/10.1534/genetics.111.134031,PMC3213368,,,"Forward genetic screens provide a powerful approach for inferring gene function on the basis of the phenotypes associated with mutated genes. However, determining the causal mutation by traditional mapping and candidate gene sequencing is often the rate-limiting step, especially when analyzing many mutants. We report two genomic approaches for more rapidly determining the identity of the affected genes in Caenorhabditis elegans mutants. First, we report our use of restriction site-associated DNA (RAD) polymorphism markers for rapidly mapping mutations after chemical mutagenesis and mutant isolation. Second, we describe our use of genomic interval pull-down sequencing (GIPS) to selectively capture and sequence megabase-sized portions of a mutant genome. Together, these two methods provide a rapid and cost-effective approach for positional cloning of C. elegans mutant loci, and are also applicable to other genetic model systems.",,"['O’Rourke, Sean M.', 'Yochem, John', 'Connolly, Amy A.', 'Price, Meredith H.', 'Carter, Luke', 'Lowry, Joshua B.', 'Turnbull, Douglas W.', 'Kamps-Hughes, Nick', 'Stiffler, Nicholas', 'Miller, Michael R.', 'Johnson, Eric A.', 'Bowerman, Bruce']",,,,
,PMC,Medical School Hotline: Turning the Tragedy of Tobacco Around: How Revenue from Cigarettes Improves Health in Hawai‘i,,PMC3215990,,,,,"['Shelton, Tina M', 'Hedges, Jerris R']",,,,
,PMC,Workforce Integration of New Graduate Nurses: Evaluation of a Health Human Resources Employment Policy,,PMC3287948,,,"Historically, economic changes have negatively affected the nursing workforce in Ontario. The trend towards part-time and casual employment emerged from healthcare restructuring in the 1990s. The severe acute respiratory syndrome (SARS) outbreak in 2003 alerted the Ontario government to the issue of part-time and casual nursing. In 2007, the Nursing Graduate Guarantee (NGG), a health human resources employment policy, was developed as a financial incentive for employers to hire and mentor new graduate nurses for a six-month period. The purpose of this study was to examine facilitators and barriers to policy implementation and assess the impact of the NGG on full-time employment and workforce integration of new graduate nurses in Ontario. A mixed-methods approach was used and included surveys, interviews and focus groups. Results indicated that full-time employment of new graduate nurses increased during the study period and that mentorship facilitated workforce integration of new graduate nurses.",,"['Baumann, Andrea', 'Hunsberger, Mabel', 'Crea-Arsenio, Mary']",,,,
,PMC,OX40:OX40L axis: emerging targets for improving poxvirus-based CD8(+) T-cell vaccines against respiratory viruses,http://dx.doi.org/10.1111/j.1600-065X.2011.01062.x,PMC3422077,,,"The human respiratory tract is the entry point for over 200 known viruses that collectively contribute to millions of annual deaths worldwide. Consequently the World Health Organization has designated respiratory viral infections as a priority for vaccine development. Despite enormous advances in understanding the attributes of a protective mucosal antiviral immune response, current vaccines continue to fail in effectively generating long-lived protective CD8(+) T-cell immunity. To date, the majority of licensed human vaccines afford protection against infectious pathogens through the generation of specific immunoglobulin responses. In recent years, the selective manipulation of specific costimulatory pathways, which are critical in regulating T-cell-mediated immune responses, has generated increasing interest. Impressive results in animal models have shown that the tumor necrosis factor receptor (TNFR) family member OX40 (CD134) and its binding partner OX40L (CD252) are key costimulatory molecules involved in the generation of protective CD8(+) T-cell responses at mucosal surfaces such as the lung. In this review, we highlight these new findings with a particular emphasis on their potential as immunological adjuvants to enhance poxvirus-based CD8(+) T-cell vaccines.",,"['Goulding, John', 'Tahiliani, Vikas', 'Salek-Ardakani, Shahram']",,,,
,PMC,Growing Male Rats in Individually Ventilated and Open-Top Cages,,PMC3228924,,,"During the past few decades, the development and use of individually ventilated cages (IVC), which are now commercially available for housing laboratory mice and rats, have increased. Because limited information is available regarding the influence of caging systems on the growth of rats, the present study assessed body weight and food and water consumption in growing male rats that were housed in IVC and open-top cages (OTC). We allocated 21-d-old male Wistar outbred rats (HsdOla:WI; n = 24) into 2 groups, which then were housed in pairs in IVC (n = 12) and OTC (n = 12). After an 8-d acclimatization period, body weight and food and water consumption were assessed every 3 d until the rats were 94 d old. There were no significant differences between the body weights of rats housed in IVC compared with OTC over the 65-d observation period. Food and water consumption were greater in rats housed in OTC compared with IVC, becoming significantly different when the rats were 50 and 53 d old, respectively. In conclusion, IVC and OTC housing conditions influenced food and water intakes but not body weight in growing male rats. Further research is needed to clarify the exact basis for these changes in food and water consumption.",,"['Kostomitsopoulos, Nikolaos', 'Dontas, Ismene A', 'Alexakos, Pavlos', 'Lelovas, Pavlos', 'Galanos, Antonios', 'Paronis, Euthimios', 'Balafas, Evangelos', 'Paschidis, Konstantinos', 'Kostakis, Alkiviadis']",,,,
,PMC,Viruses in diarrhoeic dogs include novel kobuviruses and sapoviruses,http://dx.doi.org/10.1099/vir.0.034611-0,PMC3352364,,,"The close interactions of dogs with humans and surrounding wildlife provide frequent opportunities for cross-species virus transmissions. In order to initiate an unbiased characterization of the eukaryotic viruses in the gut of dogs, this study used deep sequencing of partially purified viral capsid-protected nucleic acids from the faeces of 18 diarrhoeic dogs. Known canine parvoviruses, coronaviruses and rotaviruses were identified, and the genomes of the first reported canine kobuvirus and sapovirus were characterized. Canine kobuvirus, the first sequenced canine picornavirus and the closest genetic relative of the diarrhoea-causing human Aichi virus, was detected at high frequency in the faeces of both healthy and diarrhoeic dogs. Canine sapovirus constituted a novel genogroup within the genus Sapovirus, a group of viruses also associated with human and animal diarrhoea. These results highlight the high frequency of new virus detection possible even in extensively studied animal species using metagenomics approaches, and provide viral genomes for further disease-association studies.",,"['Li, Linlin', 'Pesavento, Patricia A.', 'Shan, Tongling', 'Leutenegger, Christian M.', 'Wang, Chunlin', 'Delwart, Eric']",,,,
,PMC,Cyclosporin A inhibits the replication of diverse coronaviruses,http://dx.doi.org/10.1099/vir.0.034983-0,PMC3352363,,,"Low micromolar, non-cytotoxic concentrations of cyclosporin A (CsA) strongly affected the replication of severe acute respiratory syndrome coronavirus (SARS-CoV), human coronavirus 229E and mouse hepatitis virus in cell culture, as was evident from the strong inhibition of GFP reporter gene expression and a reduction of up to 4 logs in progeny titres. Upon high-multiplicity infection, CsA treatment rendered SARS-CoV RNA and protein synthesis almost undetectable, suggesting an early block in replication. siRNA-mediated knockdown of the expression of the prominent CsA targets cyclophilin A and B did not affect SARS-CoV replication, suggesting either that these specific cyclophilin family members are dispensable or that the reduced expression levels suffice to support replication.",,"['de Wilde, Adriaan H.', 'Zevenhoven-Dobbe, Jessika C.', 'van der Meer, Yvonne', 'Thiel, Volker', 'Narayanan, Krishna', 'Makino, Shinji', 'Snijder, Eric J.', 'van Hemert, Martijn J.']",,,,
,PMC,Recombinant Vesicular Stomatitis Virus–Based Vaccines Against Ebola and Marburg Virus Infections,http://dx.doi.org/10.1093/infdis/jir349,PMC3218670,,,"The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filovirus vaccines was shown to completely protect nonhuman primates against Marburg virus and 3 different species of Ebola virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filovirus infections, and a rVSV-based Ebola virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg virus infections.",,"['Geisbert, Thomas W.', 'Feldmann, Heinz']",,,,
,PMC,The Ebola Virus Glycoprotein and HIV-1 Vpu Employ Different Strategies to Counteract the Antiviral Factor Tetherin,http://dx.doi.org/10.1093/infdis/jir378,PMC3189996,,,"The antiviral protein tetherin/BST2/CD317/HM1.24 restricts cellular egress of human immunodeficiency virus (HIV) and of particles mimicking the Ebola virus (EBOV), a hemorrhagic fever virus. The HIV-1 viral protein U (Vpu) and the EBOV-glycoprotein (EBOV-GP) both inhibit tetherin. Here, we compared tetherin counteraction by EBOV-GP and Vpu. We found that EBOV-GP but not Vpu counteracted tetherin from different primate species, indicating that EBOV-GP and Vpu target tetherin differentially. Tetherin interacted with the GP2 subunit of EBOV-GP, which might encode the determinants for tetherin counteraction. Vpu reduced cell surface expression of tetherin while EBOV-GP did not, suggesting that both proteins employ different mechanisms to counteract tetherin. Finally, Marburg virus (MARV)–GP also inhibited tetherin and downregulated tetherin in a cell type–dependent fashion, indicating that tetherin antagonism depends on the cellular source of tetherin. Collectively, our results indicate that EBOV-GP counteracts tetherin by a novel mechanism and that tetherin inhibition is conserved between EBOV-GP and MARV-GP.",,"['Kühl, Annika', 'Banning, Carina', 'Marzi, Andrea', 'Votteler, Jörg', 'Steffen, Imke', 'Bertram, Stephanie', 'Glowacka, Ilona', 'Konrad, Andreas', 'Stürzl, Michael', 'Guo, Ju-Tao', 'Schubert, Ulrich', 'Feldmann, Heinz', 'Behrens, Georg', 'Schindler, Michael', 'Pöhlmann, Stefan']",,,,
,PMC,Comparative Analysis of Ebola Virus Glycoprotein Interactions With Human and Bat Cells,http://dx.doi.org/10.1093/infdis/jir306,PMC3189982,,,"Infection with Ebola virus (EBOV) causes hemorrhagic fever in humans with high case-fatality rates. The EBOV-glycoprotein (EBOV-GP) facilitates viral entry and promotes viral release from human cells. African fruit bats are believed not to develop disease upon EBOV infection and have been proposed as a natural reservoir of EBOV. We compared EBOV-GP interactions with human cells and cells from African fruit bats. We found that susceptibility to EBOV-GP–dependent infection was not limited to bat cells from potential reservoir species, and we observed that GP displayed similar biological properties in human and bat cells. The only exception was GP localization, which was to a greater extent intracellular in bat cells as compared to human cells. Collectively, our results suggest that GP interactions with fruit bat and human cells are similar and do not limit EBOV tropism for certain bat species.",,"['Kühl, Annika', 'Hoffmann, Markus', 'Müller, Marcel A.', 'Munster, Vincent J.', 'Gnirß, Kerstin', 'Kiene, Miriam', 'Tsegaye, Theodros Solomon', 'Behrens, Georg', 'Herrler, Georg', 'Feldmann, Heinz', 'Drosten, Christian', 'Pöhlmann, Stefan']",,,,
,PMC,Infection of Calves with Bovine Norovirus GIII.1 Strain Jena Virus: an Experimental Model To Study the Pathogenesis of Norovirus Infection,http://dx.doi.org/10.1128/JVI.05342-11,PMC3209315,,,"The experimental infection of newborn calves with bovine norovirus was used as a homologous large animal model to study the pathogenesis of norovirus infection and to determine target cells for viral replication. Six newborn calves were inoculated orally with Jena virus (JV), a bovine norovirus GIII.1 strain, and six calves served as mock-inoculated controls. Following infection, calves were euthanized before the onset of diarrhea (12 h postinoculation [hpi]), shortly after the onset of diarrhea (18 to 21 hpi), and postconvalescence (4 days pi [dpi]). Calves inoculated with JV developed severe watery diarrhea at 14 to 16 hpi, and this symptom lasted for 53.5 to 67.0 h. Intestinal lesions were characterized by severe villus atrophy together with loss and attenuation of villus epithelium. Viral capsid antigen (JV antigen) was detected by immunohistochemistry in the cytoplasm of epithelial cells on villi. In addition, granular material positive for JV antigen was detected in the lamina propria of villi. Lesions first appeared at 12 hpi and were most extensive at 18 to 19 hpi, extending from midjejunum to ileum. The intestinal mucosa had completely recovered at 4 dpi. There was no indication of systemic infection as described for norovirus infection in mice. JV was found in intestinal contents by reverse transcription-PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) as early as 12 hpi. Fecal shedding of the virus started at 13 hpi and stopped at 23 hpi or at necropsy (4 dpi), respectively. Throughout the trial, none of the control calves tested positive for JV by ELISA or RT-PCR.",,"['Otto, Peter H.', 'Clarke, Ian N.', 'Lambden, Paul R.', 'Salim, Omar', 'Reetz, Jochen', 'Liebler-Tenorio, Elisabeth M.']",,,,
,PMC,HIV-1 Coinfection and Morphine Coexposure Severely Dysregulate Hepatitis C Virus-Induced Hepatic Proinflammatory Cytokine Release and Free Radical Production: Increased Pathogenesis Coincides with Uncoordinated Host Defenses,http://dx.doi.org/10.1128/JVI.05239-11,PMC3209310,,,"Coinfection with human immunodeficiency virus type-1 (HIV-1) and hepatitis C virus (HCV) is a global problem that is more prevalent in injection drug users because they have a higher risk for acquiring both viruses. The roles of inflammatory cytokines and oxidative stress were examined in HIV-1- and HCV-coinfected human hepatic cells. Morphine (the bioactive product of heroin), HIV-1 Tat and the MN strain gp120 (gp120(MN)) proteins, and X4 HIV-1(LAI/IIIB) and R5 HIV-1(SF162) isolates were used to study the mechanisms of disease progression in HCV (JFH1)-infected Huh7.5.1 cell populations. HCV increased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release and augmented production of reactive oxygen species (ROS), nitric oxide (NO), and 3-nitrotyrosine (3-NT) in Huh7.5.1 cells. Morphine preferentially affected R5-tropic, but not X4-tropic, HIV-1 interactions with Huh7.5.1 cells. HIV-1 proteins or isolates increased cytokine release in HCV-infected cells, while adding morphine to coinfected cells caused complex imbalances, significantly disrupting cytokine secretion depending on the cytokine, morphine concentration, exposure duration, and particular pathogen involved. Production of ROS, NO, and 3-NT increased significantly in HCV- and HIV-1-coexposed cells while exposure to morphine further increased ROS. The proteasome inhibitor MG132 significantly decreased oxyradicals, cytokine levels, and HCV protein levels. Our findings indicate that hepatic inflammation is increased by combined exposure to HCV and HIV-1, that the ubiquitin-proteasome system and NF-κB contribute to key aspects of the response, and that morphine further exacerbates the disruption of host defenses. The results suggest that opioid abuse and HIV-1 coinfection each further accelerate HCV-mediated liver disease by dysregulating immune defenses.",,"['El-Hage, Nazira', 'Dever, Seth M.', 'Fitting, Sylvia', 'Ahmed, Tasrif', 'Hauser, Kurt F.']",,,,
,PMC,Replication of the Rotavirus Genome Requires an Active Ubiquitin-Proteasome System,http://dx.doi.org/10.1128/JVI.05286-11,PMC3209302,,,"Here we show that the ubiquitin-proteasome system is required for the efficient replication of rotavirus RRV in MA104 cells. The proteasome inhibitor MG132 decreased the yield of infectious virus under conditions where it severely reduces the synthesis of not only viral but also cellular proteins. Addition of nonessential amino acids to the cell medium restored both viral protein synthesis and cellular protein synthesis, but the production of progeny viruses was still inhibited. In medium supplemented with nonessential amino acids, we showed that MG132 does not affect rotavirus entry but inhibits the replication of the viral genome. It was also shown that it prevents the efficient incorporation into viroplasms of viral polymerase VP1 and the capsid proteins VP2 and VP6, which could explain the inhibitory effect of MG132 on genome replication and infectious virus yield. We also showed that ubiquitination is relevant for rotavirus replication since the yield of rotavirus progeny in cells carrying a temperature-sensitive mutation in the E1 ubiquitin-activating enzyme was reduced at the restrictive temperature. In addition, overexpression of ubiquitin in MG132-treated MA104 cells partially reversed the effect of the inhibitor on virus yield. Altogether, these data suggest that the ubiquitin-proteasome (UP) system has a very complex interaction with the rotavirus life cycle, with both the ubiquitination and proteolytic activities of the system being relevant for virus replication.",,"['López, Tomás', 'Silva-Ayala, Daniela', 'López, Susana', 'Arias, Carlos F.']",,,,
,PMC,Complete Genome Sequence of a Coxsackievirus A22 Strain in Hong Kong Reveals a Natural Intratypic Recombination Event,http://dx.doi.org/10.1128/JVI.05944-11,PMC3209295,,,"Coxsackievirus A22 (CVA22) belongs to the species human enterovirus C in the Picornaviridae family. We report the first complete genome sequence of CVA22 with natural intratypic recombination between CVA22 prototype strain Chulman and CVA22 strain ban99-10427, identified in the stool of a patient in Hong Kong.",,"['Yip, Cyril C. Y.', 'Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Chan, Kwok-Hung', 'Yuen, Kwok-Yung']",,,,
,PMC,Human CD8(+) and CD4(+) T Cell Memory to Lymphocytic Choriomeningitis Virus Infection,http://dx.doi.org/10.1128/JVI.05477-11,PMC3209290,,,"Although cellular immunity to acute lymphocytic choriomeningitis virus (LCMV) infection has been well characterized in experimental studies in mice, the T cell response to this virus in humans is incompletely understood. Thus, we analyzed the breadths, magnitudes, and differentiation phenotypes of memory LCMV-specific CD8(+) and CD4(+) T cells in three human donors displaying a variety of disease outcomes after accidental needle stick injury or exposure to LCMV. Although only a small cohort of donors was analyzed at a single time point postinfection, several interesting observations were made. First, we were able to detect LCMV-specific CD8(+) and CD4(+) T cell responses directly ex vivo at 4 to 8 years after exposure, demonstrating the longevity of T cell memory in humans. Second, unlike in murine models of LCMV infection, we found that the breadths of memory CD8(+) and CD4(+) T cell responses were not significantly different from one another. Third, it seemed that the overall CD8(+) T cell response was augmented with increasing severity of disease, while the LCMV-specific CD4(+) T cell response magnitude was highly variable between the three different donors. Next, we found that LCMV-specific CD8(+) T cells in the three donors analyzed seemed to undergo an effector memory differentiation program distinct from that of CD4(+) T cells. Finally, the levels of expression of memory, costimulatory, and inhibitory receptors on CD8(+) and CD4(+) T cell subsets, in some instances, correlated with disease outcome. These data demonstrate for the first time LCMV-specific CD8(+) and CD4(+) T cells in infected humans and begin to provide new insights into memory T cell responses following an acute virus infection.",,"['Kotturi, Maya F.', 'Swann, Justine A.', 'Peters, Bjoern', 'Arlehamn, Cecilia Lindestam', 'Sidney, John', 'Kolla, Ravi V.', 'James, Eddie A.', 'Akondy, Rama S.', 'Ahmed, Rafi', 'Kwok, William W.', 'Buchmeier, Michael J.', 'Sette, Alessandro']",,,,
,PMC,Emerging Theme: Cellular PDZ Proteins as Common Targets of Pathogenic Viruses,http://dx.doi.org/10.1128/JVI.05410-11,PMC3209276,,,"More than a decade ago, three viral oncoproteins, adenovirus type 9 E4-ORF1, human T-lymphotropic virus type 1 Tax, and high-risk human papillomavirus E6, were found to encode a related carboxyl-terminal PDZ domain-binding motif (PBM) that mediates interactions with a select group of cellular PDZ proteins. Recent studies have shown that many other viruses also encode PBM-containing proteins that bind to cellular PDZ proteins. Interestingly, these recently recognized viruses include not only some with oncogenic potential (hepatitis B virus, rhesus papillomavirus, cottontail rabbit papillomavirus) but also many without this potential (influenza virus, Dengue virus, tick-borne encephalitis virus, rabies virus, severe acute respiratory syndrome coronavirus, human immunodeficiency virus). Examination of the cellular PDZ proteins that are targets of viral PBMs reveals that the viral proteins often interact with the same or similar types of PDZ proteins, most notably Dlg1 and other members of the membrane-associated guanylate kinase protein family, as well as Scribble. In addition, cellular PDZ protein targets of viral PBMs commonly control tight junction formation, cell polarity establishment, and apoptosis. These findings reveal a new theme in virology wherein many different virus families encode proteins that bind and perturb the function of cellular PDZ proteins. The inhibition or perturbation of the function of cellular PDZ proteins appears to be a widely used strategy for viruses to enhance their replication, disseminate in the host, and transmit to new hosts.",,"['Javier, Ronald T.', 'Rice, Andrew P.']",,,,
,PMC,The Fecal Virome of Pigs on a High-Density Farm,http://dx.doi.org/10.1128/JVI.05217-11,PMC3209269,,,"Swine are an important source of proteins worldwide but are subject to frequent viral outbreaks and numerous infections capable of infecting humans. Modern farming conditions may also increase viral transmission and potential zoonotic spread. We describe here the metagenomics-derived virome in the feces of 24 healthy and 12 diarrheic piglets on a high-density farm. An average of 4.2 different mammalian viruses were shed by healthy piglets, reflecting a high level of asymptomatic infections. Diarrheic pigs shed an average of 5.4 different mammalian viruses. Ninety-nine percent of the viral sequences were related to the RNA virus families Picornaviridae, Astroviridae, Coronaviridae, and Caliciviridae, while 1% were related to the small DNA virus families Circoviridae, and Parvoviridae. Porcine RNA viruses identified, in order of decreasing number of sequence reads, consisted of kobuviruses, astroviruses, enteroviruses, sapoviruses, sapeloviruses, coronaviruses, bocaviruses, and teschoviruses. The near-full genomes of multiple novel species of porcine astroviruses and bocaviruses were generated and phylogenetically analyzed. Multiple small circular DNA genomes encoding replicase proteins plus two highly divergent members of the Picornavirales order were also characterized. The possible origin of these viral genomes from pig-infecting protozoans and nematodes, based on closest sequence similarities, is discussed. In summary, an unbiased survey of viruses in the feces of intensely farmed animals revealed frequent coinfections with a highly diverse set of viruses providing favorable conditions for viral recombination. Viral surveys of animals can readily document the circulation of known and new viruses, facilitating the detection of emerging viruses and prospective evaluation of their pathogenic and zoonotic potentials.",,"['Shan, Tongling', 'Li, Linlin', 'Simmonds, Peter', 'Wang, Chunlin', 'Moeser, Adam', 'Delwart, Eric']",,,,
,PMC,Crystal Structure of Swine Major Histocompatibility Complex Class I SLA-1*0401 and Identification of 2009 Pandemic Swine-Origin Influenza A H1N1 Virus Cytotoxic T Lymphocyte Epitope Peptides,http://dx.doi.org/10.1128/JVI.05040-11,PMC3209268,,,"The presentation of viral epitopes to cytotoxic T lymphocytes (CTLs) by swine leukocyte antigen class I (SLA I) is crucial for swine immunity. To illustrate the structural basis of swine CTL epitope presentation, the first SLA crystal structures, SLA-1*0401, complexed with peptides derived from either 2009 pandemic H1N1 (pH1N1) swine-origin influenza A virus (S-OIV(NW9); NSDTVGWSW) or Ebola virus (Ebola(AY9); ATAAATEAY) were determined in this study. The overall peptide–SLA-1*0401 structures resemble, as expected, the general conformations of other structure-solved peptide major histocompatibility complexes (pMHC). The major distinction of SLA-1*0401 is that Arg(156) has a “one-ballot veto” function in peptide binding, due to its flexible side chain. S-OIV(NW9) and Ebola(AY9) bind SLA-1*0401 with similar conformations but employ different water molecules to stabilize their binding. The side chain of P7 residues in both peptides is exposed, indicating that the epitopes are “featured” peptides presented by this SLA. Further analyses showed that SLA-1*0401 and human leukocyte antigen (HLA) class I HLA-A*0101 can present the same peptides, but in different conformations, demonstrating cross-species epitope presentation. CTL epitope peptides derived from 2009 pandemic S-OIV were screened and evaluated by the in vitro refolding method. Three peptides were identified as potential cross-species influenza virus (IV) CTL epitopes. The binding motif of SLA-1*0401 was proposed, and thermostabilities of key peptide–SLA-1*0401 complexes were analyzed by circular dichroism spectra. Our results not only provide the structural basis of peptide presentation by SLA I but also identify some IV CTL epitope peptides. These results will benefit both vaccine development and swine organ-based xenotransplantation.",,"['Zhang, Nianzhi', 'Qi, Jianxun', 'Feng, Sijia', 'Gao, Feng', 'Liu, Jun', 'Pan, Xiaocheng', 'Chen, Rong', 'Li, Qirun', 'Chen, Zhaosan', 'Li, Xiaoying', 'Xia, Chun', 'Gao, George F.']",,,,
,PMC,Cross-Reactive HIV-1-Neutralizing Human Monoclonal Antibodies Identified from a Patient with 2F5-Like Antibodies,http://dx.doi.org/10.1128/JVI.05312-11,PMC3194990,,,"The genes encoding broadly HIV-1-neutralizing human monoclonal antibodies (MAbs) are highly divergent from their germ line counterparts. We have hypothesized that such high levels of somatic hypermutation could pose a challenge for elicitation of the broadly neutralizing (bn) Abs and that identification of less somatically mutated bn Abs may help in the design of effective vaccine immunogens. In a quest for such bn Abs, phage- and yeast-displayed antibody libraries, constructed using peripheral blood mononuclear cells (PBMCs) from a patient with bn serum containing Abs targeting the epitope of the bn MAb 2F5, were panned against peptides containing the 2F5 epitope and against the HIV-1 gp140(JR-FL). Two MAbs (m66 and m66.6) were identified; the more mutated variant (m66.6) exhibited higher HIV-1-neutralizing activity than m66, although it was weaker than 2F5 in a TZM-bl cell assay. Binding of both MAbs to gp41 alanine substitution mutant peptides required the DKW(664–666) core of the 2F5 epitope and two additional upstream residues (L(660,663)). The MAbs have long (21-residue) heavy-chain third complementarity-determining regions (CDR-H3s), and m66.6 (but not m66) exhibited polyspecific reactivity to self- and non-self-antigens. Both m66 and m66.6 are significantly less divergent from their germ line Ab counterparts than 2F5—they have a total of 11 and 18 amino acid changes, respectively, from the closest VH and Vκ germ line gene products compared to 25 for 2F5. These new MAbs could help explore the complex maturation pathways involved in broad neutralization and its relationship with auto- and polyreactivity and may aid design of vaccine immunogens and development of therapeutics against HIV-1 infection.",,"['Zhu, Zhongyu', 'Qin, Haiyan Rebekah', 'Chen, Weizao', 'Zhao, Qi', 'Shen, Xiaoying', 'Schutte, Robert', 'Wang, Yanping', 'Ofek, Gilad', 'Streaker, Emily', 'Prabakaran, Ponraj', 'Fouda, Genevieve G.', 'Liao, Hua-Xin', 'Owens, John', 'Louder, Mark', 'Yang, Yongping', 'Klaric, Kristina-Ana', 'Moody, M. Anthony', 'Mascola, John R.', 'Scott, Jamie K.', 'Kwong, Peter D.', 'Montefiori, David', 'Haynes, Barton F.', 'Tomaras, Georgia D.', 'Dimitrov, Dimiter S.']",,,,
,PMC,Varicella-Zoster Virus Immediate-Early Protein ORF61 Abrogates the IRF3-Mediated Innate Immune Response through Degradation of Activated IRF3,http://dx.doi.org/10.1128/JVI.05098-11,PMC3194975,,,"Varicella-zoster virus (VZV) infection of differentiated cells within the host and establishment of latency likely requires evasion of innate immunity and limits secretion of antiviral cytokines. Here we report that its immediate-early protein ORF61 antagonizes the beta interferon (IFN-β) pathway. VZV infection down-modulated the Sendai virus (SeV)-activated IFN-β pathway, including mRNA of IFN-β and its downstream interferon-stimulated genes (ISGs), ISG54 and ISG56. Through a primary screening of VZV genes, we found that ORF61 inhibited SeV-mediated activation of IFN-β and ISRE (IFN-stimulated response element) promoter activities but only slightly affected NF-κB promoter activity, implying that the IFN-β pathway may be blocked in the IRF3 branch. An indirect immunofluorescence assay demonstrated that ectopic expression of ORF61 abrogated the detection of IRF3 in SeV-infected cells; however, it did not affect endogenous dormant IRF3 in noninfected cells. Additionally, ORF61 was shown to be partially colocalized with activated IRF3 in the nucleus upon treatment with MG132, an inhibitor of proteasomes, and the direct interaction between ORF61 and activated IRF3 was confirmed by a coimmunoprecipitation assay. Furthermore, Western blot analysis demonstrated that activated IRF3 was ubiquitinated in the presence of ORF61, suggesting that ORF61 degraded phosphorylated IRF3 via a ubiquitin-proteasome pathway. Semiquantitative reverse transcription-PCR (RT-PCR) analysis demonstrated that the level of ISG54 and ISG56 mRNAs was also downregulated by ORF61. Taken together, our results convincingly demonstrate that ORF61 down-modulates the IRF3-mediated IFN-β pathway by degradation of activated IRF3 via direct interaction, which may contribute to the pathogenesis of VZV infection.",,"['Zhu, Huifang', 'Zheng, Chunfu', 'Xing, Junji', 'Wang, Shuai', 'Li, Shuping', 'Lin, Rongtuan', 'Mossman, Karen L.']",,,,
,PMC,"Fatal Outcome of Pandemic H1N1 2009 Influenza Virus Infection Is Associated with Immunopathology and Impaired Lung Repair, Not Enhanced Viral Burden, in Pregnant Mice",http://dx.doi.org/10.1128/JVI.00654-11,PMC3194964,,,"Pandemic A (H1N1) 2009 influenza virus (pH1N1) infection in pregnant women can be severe. The mechanisms that affect infection outcome in this population are not well understood. To address this, pregnant and nonpregnant BALB/c mice were inoculated with the wild-type pH1N1 strain A/California/04/09. To determine whether innate immune responses are associated with severe infection, we measured the innate cells trafficking into the lungs of pregnant versus nonpregnant animals. Increased infiltration of pulmonary neutrophils and macrophages strongly correlated with an elevated mortality in pregnant mice. In agreement with this, the product of nitric oxide (nitrite) and several cytokines associated with recruitment and/or function of these cells were increased in the lungs of pregnant animals. Surprisingly, increased mortality in pregnant mice was not associated with higher virus load because equivalent virus titers and immunohistochemical staining were observed in the nasal cavities or lungs of all mice. To determine whether exacerbated inflammatory responses and elevated cellularity resulted in lung injury, epithelial regeneration was measured. The lungs of pregnant mice exhibited reduced epithelial regeneration, suggesting impaired lung repair. Despite these immunologic alterations, pregnant animals demonstrated equivalent percentages of pulmonary influenza virus-specific CD8(+) T lymphocytes, although they displayed elevated levels of T-regulator lymphocytes (Tregs) in the lung. Also, pregnant mice mounted equal antibody titers in response to virus or immunization with a monovalent inactivated pH1N1 A/California/07/09 vaccine. Therefore, immunopathology likely caused by elevated cellular recruitment is an implicated mechanism of severe pH1N1 infection in pregnant mice.",,"['Marcelin, Glendie', 'Aldridge, Jerry R.', 'Duan, Susu', 'Ghoneim, Hazem E.', 'Rehg, Jerold', 'Marjuki, Henju', 'Boon, Adrianus C. M.', 'McCullers, Jonathan A.', 'Webby, Richard J.']",,,,
,PMC,Mechanism of Glycyrrhizic Acid Inhibition of Kaposi's Sarcoma-Associated Herpesvirus: Disruption of CTCF-Cohesin-Mediated RNA Polymerase II Pausing and Sister Chromatid Cohesion,http://dx.doi.org/10.1128/JVI.00720-11,PMC3194953,,,"Glycyrrhizic acid (GA), a derivative of licorice, selectively inhibits the growth of lymphocytes latently infected with Kaposi's sarcoma-associated herpesvirus. The mechanism involves the deregulation of the multicistronic latency transcript, including the failure to generate the mature forms of viral mRNA encoding LANA. We show here that GA disrupts an RNA polymerase II (RNAPII) complex that accumulates at the CTCF-cohesin binding site within the first intron of the latency transcript. GA altered the enrichment of the RNAPII pausing complex, along with pausing factors SPT5 and NELF-A, at the intragenic CTCF-cohesin binding sites. GA blocked the interaction of cohesin subunit SMC3 with another cohesin subunit, RAD21, and reduced SPT5 interaction with RNAPII. Covalent coupling of GA to a solid support revealed that GA interacts with several cellular proteins, including SMC3 and SPT5, but not their respective interaction partners RAD21 and RNAPII. GA treatment also inhibited the transcription of some cellular genes, like c-myc, which contain a similar CTCF-cohesin binding site within the first intron. We also found that GA leads to a more general loss of sister chromatid cohesion for cellular chromosomes. These findings suggest that RNAPII pauses at intragenic CTCF-cohesin binding sites and that abrogation of this pausing by GA leads to loss of proper mRNA production and defects in sister chromatid cohesion, a process important for both viral and cellular chromosome stability.",,"['Kang, Hyojeung', 'Lieberman, Paul M.']",,,,
,PMC,Molecular Epidemiology of Human Coronavirus OC43 Reveals Evolution of Different Genotypes over Time and Recent Emergence of a Novel Genotype due to Natural Recombination,http://dx.doi.org/10.1128/JVI.05512-11,PMC3194943,,,"Although human coronavirus OC43-OC43 (HCoV-OC43) is the coronavirus most commonly associated with human infections, little is known about its molecular epidemiology and evolution. We conducted a molecular epidemiology study to investigate different genotypes and potential recombination in HCoV-OC43. Twenty-nine HCoV-OC43 strains from nasopharyngeal aspirates, collected from 2004 to 2011, were subjected to RNA-dependent RNA polymerase (RdRp), spike, and nucleocapsid gene analysis. Phylogenetic analysis showed at least three distinct clusters of HCoV-OC43, although 10 unusual strains displayed incongruent phylogenetic positions between RdRp and spike genes. This suggested the presence of four HCoV-OC43 genotypes (A to D), with genotype D most likely arising from recombination. The complete genome sequencing of two genotype C and D strains and bootscan analysis showed recombination events between genotypes B and C in the generation of genotype D. Of the 29 strains, none belonged to the more ancient genotype A, 5 from 2004 belonged to genotype B, 15 from 2004 to 2006 belonged to genotype C, and 1 from 2004 and all 8 from 2008 to 2011 belonged to the recombinant genotype D. Molecular clock analysis using spike and nucleocapsid genes dated the most recent common ancestor of all genotypes to the 1950s, genotype B and C to the 1980s, genotype B to the 1990s, and genotype C to the late 1990s to early 2000s, while the recombinant genotype D strains were detected as early as 2004. This represents the first study to describe natural recombination in HCoV-OC43 and the evolution of different genotypes over time, leading to the emergence of novel genotype D, which is associated with pneumonia in our elderly population.",,"['Lau, Susanna K. P.', 'Lee, Paul', 'Tsang, Alan K. L.', 'Yip, Cyril C. Y.', 'Tse, Herman', 'Lee, Rodney A.', 'So, Lok-Yee', 'Lau, Yu-Lung', 'Chan, Kwok-Hung', 'Woo, Patrick C. Y.', 'Yuen, Kwok-Yung']",,,,
,PMC,Complete Genome Sequence of a Chinese Virulent Porcine Epidemic Diarrhea Virus Strain,http://dx.doi.org/10.1128/JVI.06024-11,PMC3194942,,,"CH/S is a virulent porcine epidemic diarrhea virus (PEDV) strain and is used as the virulent strain to evaluate the protection rates of vaccines against PEDV infection in China. Here, we report the complete genome sequence of strain CH/S, which may aid in understanding the molecular characteristics of this strain.",,"['Chen, Jianfei', 'Wang, Chengbao', 'Shi, Hongyan', 'Qiu, Hua-Ji', 'Liu, Shengwang', 'Shi, Da', 'Zhang, Xin', 'Feng, Li']",,,,
,PMC,Identification of the Myelin Oligodendrocyte Glycoprotein as a Cellular Receptor for Rubella Virus,http://dx.doi.org/10.1128/JVI.05398-11,PMC3194935,,,"Rubella virus (RV) is a highly transmissible pathogenic agent that causes the disease rubella. Maternal RV infection during early pregnancy causes the death of the fetus or congenital rubella syndrome in infants. However, the cellular receptor for RV has not yet been identified. In this study, we found that the myelin oligodendrocyte glycoprotein (MOG) specifically bound to the E1 envelope glycoprotein of RV, and an antibody against MOG could block RV infection. Most importantly, we also showed that ectopic expression of MOG on the cell surface of 293T cells rendered this nonpermissive cell line permissive for RV entry and replication. Thus, this study has identified a cellular receptor for RV and suggests that blocking the MOG attachment site of RV may be a strategy for molecular intervention of RV infection.",,"['Cong, Haolong', 'Jiang, Yue', 'Tien, Po']",,,,
,PMC,Mechanism for Noncompetitive Inhibition by Novel GluN2C/D N-Methyl-d-aspartate Receptor Subunit-Selective Modulators,http://dx.doi.org/10.1124/mol.111.073239,PMC3198917,,,"The compound 4-(5-(4-bromophenyl)-3-(6-methyl-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoic acid (DQP-1105) is a representative member of a new class of N-methyl-d-aspartate (NMDA) receptor antagonists. DQP-1105 inhibited GluN2C- and GluN2D-containing receptors with IC(50) values that were at least 50-fold lower than those for recombinant GluN2A-, GluN2B-, GluA1-, or GluK2-containing receptors. Inhibition was voltage-independent and could not be surmounted by increasing concentrations of either coagonist, glutamate or glycine, consistent with a noncompetitive mechanism of action. DQP-1105 inhibited single-channel currents in excised outside-out patches without significantly changing mean open time or single-channel conductance, suggesting that DQP inhibits a pregating step without changing the stability of the open pore conformation and thus channel closing rate. Evaluation of DQP-1105 inhibition of chimeric NMDA receptors identified two key residues in the lower lobe of the GluN2 agonist binding domain that control the selectivity of DQP-1105. These data suggest a mechanism for this new class of inhibitors and demonstrate that ligands can access, in a subunit-selective manner, a new site located in the lower, membrane-proximal portion of the agonist-binding domain.",,"['Acker, Timothy M.', 'Yuan, Hongjie', 'Hansen, Kasper B.', 'Vance, Katie M.', 'Ogden, Kevin K.', 'Jensen, Henrik S.', 'Burger, Pieter B.', 'Mullasseril, Praseeda', 'Snyder, James P.', 'Liotta, Dennis C.', 'Traynelis, Stephen F.']",,,,
,PMC,Supplies and equipment for pediatric emergency mass critical care,http://dx.doi.org/10.1097/PCC.0b013e318234a6b9,PMC4561174,,,"INTRODUCTION: Epidemics of acute respiratory disease, such as severe acute respiratory syndrome in 2003, and natural disasters, such as Hurricane Katrina in 2005, have prompted planning in hospitals that offer adult critical care to increase their capacity and equipment inventory for responding to a major demand surge. However, planning at a national, state, or local level to address the particular medical resource needs of children for mass critical care has yet to occur in any coordinated way. This paper presents the consensus opinion of the Task Force regarding supplies and equipment that would be required during a pediatric mass critical care crisis. METHODS: In May 2008, the Task Force for Mass Critical Care published guidance on provision of mass critical care to adults. Acknowledging that the critical care needs of children during disasters were unaddressed by this effort, a 17-member Steering Committee, assembled by the Oak Ridge Institute for Science and Education with guidance from members of the American Academy of Pediatrics, convened in April 2009 to determine priority topic areas for pediatric emergency mass critical care recommendations. Steering Committee members established subcommittees by topic area and performed literature reviews of MEDLINE and Ovid databases. The Steering Committee produced draft outlines through consensus-based study of the literature and convened October 6 –7, 2009, in New York, NY, to review and revise each outline. Eight draft documents were subsequently developed from the revised outlines as well as through searches of MEDLINE updated through March 2010. The Pediatric Emergency Mass Critical Care Task Force, composed of 36 experts from diverse public health, medical, and disaster response fields, convened in Atlanta, GA, on March 29 –30, 2010. Feedback on each manuscript was compiled and the Steering Committee revised each document to reflect expert input in addition to the most current medical literature. TASK FORCE RECOMMENDATIONS: The Task Force endorsed the view that supplies and equipment must be available for a tripling of capacity above the usual peak pediatric intensive care unit capacity for at least 10 days. The recommended size-specific pediatric mass critical care equipment stockpile for two types of patients is presented in terms of equipment needs per ten mass critical care beds, which would serve 26 patients over a 10-day period. Specific recommendations are made regarding ventilator capacity, including the potential use of high-frequency oscillatory ventilation and extracorporeal membrane oxygenation. Other recommendations include inventories for disposable medical equipment, medications, and staffing levels.",,"['Bohn, Desmond', 'Kanter, Robert K.', 'Burns, Jeffrey', 'Barfield, Wanda D.', 'Kissoon, Niranjan']",,,,
,PMC,Veterinary Public Health Capacity in the United States: Opportunities for Improvement,,PMC3185323,,,"OBJECTIVES: In 2006, the Association of American Veterinary Medical Colleges reported that the shortage (≥1,500) of public health veterinarians is expected to increase tenfold by 2020. In 2008, the Centers for Disease Control and Prevention (CDC) Preventive Medicine Fellows conducted a pilot project among CDC veterinarians to identify national veterinary public health workforce concerns and potential policy strategies. METHODS: Fellows surveyed a convenience sample (19/91) of public health veterinarians at CDC to identify veterinary workforce recruitment and retention problems faced by federal agencies; responses were categorized into themes. A focus group (20/91) of staff veterinarians subsequently prioritized the categorized themes from least to most important. Participants identified activities to address the three recruitment concerns with the highest combined weight. RESULTS: Participants identified the following three highest prioritized problems faced by federal agencies when recruiting veterinarians to public health: (1) lack of awareness of veterinarians' contributions to public health practice, (2) competitive salaries, and (3) employment and training opportunities. Similarly, key concerns identified regarding retention of public health practice veterinarians included: (1) lack of recognition of veterinary qualifications, (2) competitive salaries, and (3) seamless integration of veterinary and human public health. CONCLUSIONS: Findings identified multiple barriers that can affect recruitment and retention of veterinarians engaged in public health practice. Next steps should include replicating project efforts among a national sample of public health veterinarians. A committed and determined long-term effort might be required to sustain initiatives and policy proposals to increase U.S. veterinary public health capacity.",,"['Jarman, Dwayne W.', 'Liang, Jennifer L.', 'Luce, Richard R.', 'Wright, Jennifer G.', 'Stennies, Gail M.', 'Bisgard, Kristine M.']",,,,
,PMC,"Humoral Immunity to AAV-6, 8, and 9 in Normal and Dystrophic Dogs",http://dx.doi.org/10.1089/hum.2011.125,PMC3300072,,,"Adeno-associated virus (AAV)-6, 8, and 9 are promising gene-delivery vectors for testing novel Duchenne muscular dystrophy gene therapy in the canine model. Humoral immunity greatly influences in vivo AAV transduction. However, neutralizing antibodies to AAV-6, 8, and 9 have not been systemically examined in normal and dystrophic dogs. To gain information on the seroprevalence of antibodies to AAV-6, 8, and 9, we measured neutralizing antibody titers using an in vitro transduction inhibition assay. We examined 72 naive serum samples and 26 serum samples obtained from dogs that had received AAV gene transfer. Our data demonstrated that AAV-6 neutralizing antibody was the most prevalent antibody in dogs irrespective of age, gender, disease status (dystrophic or not), and prior parvovirus vaccination history. Surprisingly, high-level anti-AAV-6 antibody was detected at birth in newborn puppies. Further, a robust antibody response was induced in affected, but not normal newborn dogs following systemic AAV gene transfer. Taken together, our data have provided an important baseline on the seroprevalence of AAV-6, 8, and 9 neutralizing antibodies in normal and Duchenne muscular dystrophy dogs. These results will help guide translational AAV gene-therapy studies in dog models of muscular dystrophy.",,"['Shin, Jin-Hong', 'Yue, Yongping', 'Smith, Bruce', 'Duan, Dongsheng']",,,,
,PMC,Bayesian modeling to unmask and predict influenza A/H1N1pdm dynamics in London,http://dx.doi.org/10.1073/pnas.1103002108,PMC3215054,,,"The tracking and projection of emerging epidemics is hindered by the disconnect between apparent epidemic dynamics, discernible from noisy and incomplete surveillance data, and the underlying, imperfectly observed, system. Behavior changes compound this, altering both true dynamics and reporting patterns, particularly for diseases with nonspecific symptoms, such as influenza. We disentangle these effects to unravel the hidden dynamics of the 2009 influenza A/H1N1pdm pandemic in London, where surveillance suggests an unusual dominant peak in the summer. We embed an age-structured model into a Bayesian synthesis of multiple evidence sources to reveal substantial changes in contact patterns and health-seeking behavior throughout the epidemic, uncovering two similar infection waves, despite large differences in the reported levels of disease. We show how this approach, which allows for real-time learning about model parameters as the epidemic progresses, is also able to provide a sequence of nested projections that are capable of accurately reflecting the epidemic evolution.",,"['Birrell, Paul J.', 'Ketsetzis, Georgios', 'Gay, Nigel J.', 'Cooper, Ben S.', 'Presanis, Anne M.', 'Harris, Ross J.', 'Charlett, André', 'Zhang, Xu-Sheng', 'White, Peter J.', 'Pebody, Richard G.', 'De Angelis, Daniela']",,,,
,PMC,Age-related Deficiencies in Antigen-Specific CD4 T cell Responses: Lessons from Mouse Models,,PMC3295078,,,"Infectious diseases contribute to significant morbidity and mortality in elderly populations. One of the major contributing factors to this is age-related declines in the immune system that diminish the response o both infections and vaccinations. In order to understand how specific changes in the immune system influence the generation of immunity in older individuals, immunologists have developed aging mouse models that allow for experimental manipulation of immune system components. These models have shown that there are dramatic age-related changes in naive CD4 T cell function that have the potential to impact a myriad of immune responses. In this review, we will summarize these findings on the intrinsic changes in CD4 T cell function and discuss how these changes influence immunity.",,"['Haynes, Laura', 'Lefebvre, Julie S.']",,,,
,PMC,Expression of type I interferon by splenic macrophages suppresses adaptive immunity during sepsis,http://dx.doi.org/10.1038/emboj.2011.380,PMC3252580,,,"Early during Gram-negative sepsis, excessive release of pro-inflammatory cytokines can cause septic shock that is often followed by a state of immune paralysis characterized by the failure to mount adaptive immunity towards secondary microbial infections. Especially, the early mechanisms responsible for such immune hypo-responsiveness are unclear. Here, we show that TLR4 is the key immune sensing receptor to initiate paralysis of T-cell immunity after bacterial sepsis. Downstream of TLR4, signalling through TRIF but not MyD88 impaired the development of specific T-cell immunity against secondary infections. We identified type I interferon (IFN) released from splenic macrophages as the critical factor causing T-cell immune paralysis. Early during sepsis, type I IFN acted selectively on dendritic cells (DCs) by impairing antigen presentation and secretion of pro-inflammatory cytokines. Our results reveal a novel immune regulatory role for type I IFN in the initiation of septic immune paralysis, which is distinct from its well-known immune stimulatory effects. Moreover, we identify potential molecular targets for therapeutic intervention to overcome impairment of T-cell immunity after sepsis.",,"['Schwandt, Timo', 'Schumak, Beatrix', 'Gielen, Gerrit H', 'Jüngerkes, Frank', 'Schmidbauer, Patricia', 'Klocke, Katrin', 'Staratschek-Jox, Andrea', 'van Rooijen, Niko', 'Kraal, Georg', 'Ludwig-Portugall, Isis', 'Franken, Lars', 'Wehner, Sven', 'Kalff, Jörg C', 'Weber, Olaf', 'Kirschning, Carsten', 'Coch, Christoph', 'Kalinke, Ulrich', 'Wenzel, Jörg', 'Kurts, Christian', 'Zawatzky, Rainer', 'Holzmann, Bernhard', 'Layland, Laura', 'Schultze, Joachim L', 'Burgdorf, Sven', 'den Haan, Joke MM', 'Knolle, Percy A', 'Limmer, Andreas']",,,,
,PMC,DDX1 is an RNA-dependent ATPase Involved in HIV-1 Rev Function and Virus Replication,http://dx.doi.org/10.1016/j.jmb.2011.10.032,PMC3249508,,,"The HIV-1 Rev protein is essential for the virus because it promotes nuclear export of alternatively-processed mRNAs, and Rev is also linked to translation of viral mRNAs and genome encapsidation. Previously, the human DEAD-box helicase DDX1 was suggested to be involved in Rev functions, but this relationship is not well understood. Biochemical studies of DDX1 and its interactions with Rev and model RNA oligonucleotides were carried out to investigate the molecular basis for association of these components. A combination of gel-filtration chromatography and circular dichroism spectroscopy demonstrated that recombinant DDX1 expressed in E. coli is a well-behaved folded protein. Binding assays using fluorescently-labeled Rev and cell-based immunoprecipitation analysis confirmed a specific RNA-independent DDX1-Rev interaction. Additionally, DDX1 was shown to be an RNA-activated ATPase, wherein Rev-bound RNA was equally effective at stimulating ATPase activity as protein-free RNA. Gel mobility shift assays further demonstrated that DDX1 forms complexes with Rev-bound RNA. RNA silencing of DDX1 provided strong evidence that DDX1 is required for both Rev activity and HIV production from infected cells. Collectively, these studies demonstrate a clear link between DDX1 and HIV-1 Rev in cell based assays of HIV-1 production, and provide the first demonstration that recombinant DDX1 binds Rev and RNA, and has RNA dependent catalytic activity.",,"['Edgcomb, Stephen P.', 'Carmel, Andrew B.', 'Naji, Souad', 'Ambrus-Aikelin, Geza', 'Reyes, Jason R.', 'Saphire, Andrew C.S.', 'Gerace, Larry', 'Williamson, James R.']",,,,
,PMC,Manipulation or capitulation: virus interactions with autophagy,http://dx.doi.org/10.1016/j.micinf.2011.09.007,PMC3264745,,,"Autophagy is a homeostatic process that functions to balance cellular metabolism and promote cell survival during stressful conditions by delivering cytoplasmic components for lysosomal degradation and subsequent recycling. During viral infection, autophagy can act as a surveillance mechanism that delivers viral antigens to the endosomal/lysosomal compartments that are enriched in immune sensors. Additionally, activated immune sensors can signal to activate autophagy. To evade this antiviral activity, many viruses elaborate functions to block the autophagy pathway at a variety of steps. Alternatively, some viruses actively subvert autophagy for their own benefit. Manipulated autophagy has been proposed to facilitate nearly every stage of the viral lifecycle in direct and indirect ways. In this review, we synthesize the extensive literature on virus-autophagy interactions, emphasizing the role of autophagy in antiviral immunity and the mechanisms by which viruses subvert autophagy for their own benefit.",,"['Jordan, Tristan X.', 'Randall, Glenn']",,,,
,PMC,Ribosomal frameshifting into an overlapping gene in the 2B-encoding region of the cardiovirus genome,http://dx.doi.org/10.1073/pnas.1102932108,PMC3219106,,,"The genus Cardiovirus (family Picornaviridae) currently comprises the species Encephalomyocarditis virus (EMCV) and Theilovirus. Cardioviruses have a positive-sense, single-stranded RNA genome that encodes a large polyprotein (L-1ABCD-2ABC-3ABCD) that is cleaved to produce approximately 12 mature proteins. We report on a conserved ORF that overlaps the 2B-encoding sequence of EMCV in the +2 reading frame. The ORF is translated as a 128–129 amino acid transframe fusion (2B*) with the N-terminal 11–12 amino acids of 2B, via ribosomal frameshifting at a conserved GGUUUUY motif. Mutations that knock out expression of 2B* result in a small-plaque phenotype. Curiously, although theilovirus sequences lack a long ORF in the +2 frame at this genomic location, they maintain a conserved GGUUUUU motif just downstream of the 2A-2B junction, and a highly localized peak in conservation at polyprotein-frame synonymous sites suggests that theiloviruses also utilize frameshifting here, albeit into a very short +2-frame ORF. Unlike previous cases of programmed -1 frameshifting, here frameshifting is modulated by virus infection, thus suggesting a novel regulatory role for frameshifting in these viruses.",,"['Loughran, Gary', 'Firth, Andrew E.', 'Atkins, John F.']",,,,
,PMC,Induction and evasion of type I interferon responses by influenza viruses,http://dx.doi.org/10.1016/j.virusres.2011.10.017,PMC3640439,,,"Influenza A and B viruses are a major cause of respiratory disease in humans. In addition, influenza A viruses continuously re-emerge from animal reservoirs into humans causing human pandemics every 10–50 years of unpredictable severity. Among the first lines of defense against influenza virus infection, the type I interferon (IFN) response plays a major role. In the last 10 years, there have been major advances in understanding how cells recognize being infected by influenza viruses, leading to secretion of type I IFN, and on the effector mechanisms by how IFN exerts its antiviral activity. In addition, we also now know that influenza virus uses multiple mechanisms to attenuate the type I IFN response, allowing for successful infection of their hosts. This review highlights some of these findings and illustrates future research avenues that might lead to new vaccines and antivirals based on the further understanding of the mechanisms of induction and evasion of type I IFN responses by influenza viruses.",,"García-Sastre, Adolfo",,,,
,PMC,Evaluation of Different Strategies for Post-Exposure Treatment of Ebola Virus Infection in Rodents,,PMC3509938,,,"Zaire Ebola virus (ZEBOV) is a pathogen that causes severe hemorrhagic fever in humans and non-human primates. There are currently no licensed vaccines or approved treatments available against ZEBOV infections. The goal of this work was to evaluate different treatment strategies in conjunction with a replication deficient, recombinant human adenovirus serotype 5-based vaccine expressing the Zaire Ebola virus glycoprotein (Ad-CAGoptZGP) in Ebola infected mice and guinea pigs. Guinea pigs were treated with Ad-CAGoptZGP in combination with different treatment strategies after challenge with guinea pig adapted-ZEBOV (GA-ZEBOV). B10.BR mice were used to further characterize efficacy and immune responses following co-administration of Ad-CAGoptZGP with the most effective treatment: AdHu5 expressing recombinant IFN-α (hereafter termed DEF201) after challenge with a lethal dose of mouse adapted-ZEBOV (MA-ZEBOV). In mice, DEF201 treatment was able to elicit full protection against a lethal dose of MA-ZEBOV when administered 30 minutes after infection. In guinea pigs the Ad-CAGoptZGP and DEF201 combination therapy elicited full protection when treated 30 minutes post-exposure and were a superior treatment to Ad-CAGoptZGP supplemented with recombinant IFN-α protein. Further analysis of the immune response revealed that addition of DEF201 to Ad-CAGoptZGP enhances the resulting adaptive immune response against ZGP. The results highlight the importance of the innate immune response in the prevention of ZEBOV pathogenesis and support further development of the Ad-CAGoptZGP with DEF201 treatment combination for post-exposure therapy against ZEBOV infection.",,"['Richardson, Jason S.', 'Wong, Gary', 'Pillet, Stéphane', 'Schindle, Samantha', 'Ennis, Jane', 'Turner, Jeffrey', 'Strong, James E.', 'Kobinger, Gary P.']",,,,
,PMC,CD133作为肺癌干细胞标记物的应用及其局限性,http://dx.doi.org/10.3779/j.issn.1009-3419.2011.10.10,PMC5999939,,,"Lung cancer is one of the most common tumor, which lacks of effective clinical treatment to lead to desirable prognosis. According to cancer stem cell hypothesis, lung cancer stem cells are considered to be responsible for carcinogenesis, development, metastasis, recurrence, invasion, resistance to chemotherapy and radiotherapy of lung cancer. In recent years, more and more institutes used glycosylated CD133 epitopes to define, isolate, purify lung cancer stem cells. However, along with deeply research, the application of CD133 epitopes in lung cancer stem cell research is questioned. The utilization and limitation of CD133 epitopes in lung cancer stem cells research for the past few years is summaried in this review.",,,,,,
,PMC,Evaluation of Monkeypox Disease Progression by Molecular Imaging,http://dx.doi.org/10.1093/infdis/jir663,PMC3209815,,,"Infection of nonhuman primates (NHPs) with monkeypox virus (MPXV) is currently being developed as an animal model of variola infection in humans. We used positron emission tomography and computed tomography (PET/CT) to identify inflammatory patterns as predictors for the outcome of MPXV disease in NHPs. Two NHPs were sublethally inoculated by the intravenous (IV) or intrabronchial (IB) routes and imaged sequentially using fluorine-18 fluorodeoxyglucose ((18)FDG) uptake as a nonspecific marker of inflammation/immune activation. Inflammation was observed in the lungs of IB-infected NHPs, and bilobular involvement was associated with morbidity. Lymphadenopathy and immune activation in the axillary lymph nodes were evident in IV- and IB-infected NHPs. Interestingly, the surviving NHPs had significant (18)FDG uptake in the axillary lymph nodes at the time of MPXV challenge with no clinical signs of illness, suggesting an association between preexisting immune activation and survival. Molecular imaging identified patterns of inflammation/immune activation that may allow risk assessment of monkeypox disease.",,"['Dyall, Julie', 'Johnson, Reed F.', 'Chen, Dar-Yeong', 'Huzella, Louis', 'Ragland, Dan R.', 'Mollura, Daniel J.', 'Byrum, Russell', 'Reba, Richard C.', 'Jennings, Gerald', 'Jahrling, Peter B.', 'Blaney, Joseph E.', 'Paragas, Jason']",,,,
,PMC,Horizontal Transfer of RNAs: Exosomes as mediators of intercellular communication,http://dx.doi.org/10.1002/wrna.115,PMC3263325,,,"Multicellular organisms are similar to biological communities, consisting of various cell types; thus, inter-cell communication is critical for the functioning of the whole system that ultimately constitutes a living being. Conventional models of cellular exchange include signaling molecules and direct contact-mediated cell communications. Exosomes, small vesicles originating from an inward budding of the plasma membrane, represent a new avenue for signaling between cells. This interchange is achieved by packaging RNA species into exosomes endowed with specific cell surface-targeting motifs. The delivered RNA molecules are functional and mRNA can be translated into new proteins, while miRNAs target host mRNAs in the recipient cell. RNA involved in transmitting information or molecules between cells is called exosomal RNA (esRNA). This review summarizes the characteristics of exosomes, specifically focusing on their role in the horizontal transfer of cellular information.",,"['Ramachandran, Saraswathi', 'Palanisamy, Viswanathan']",,,,
,PMC,"Viral and bacterial infections associated with camel (Camelus dromedarius) calf diarrhea in North Province, Saudi Arabia",http://dx.doi.org/10.1016/j.sjbs.2011.10.001,PMC3730540,,,"Diarrhea and deaths in new-born camel calves were noticed by veterinary investigators and pastoralist in Saudi Arabia to be very high. Hence, it is thought to be necessary to investigate this problem from the virological and bacteriological point of view. The role of pathogenic bacteria and viruses in six different towns of North Province (Al-Assafia, Arar, Domat Aljandal, Hail, Skaka and Khoa) in Saudi Arabia was studied. Survey was conducted in diarrheic camel calves aged 12 months or younger. In our study calf diarrhea was reported in 184 out of 2308 camels examined clinically during one year, the prevalence of diarrhea was found to be 8.0% in calves ranging from one month to one year. In the present study group A rotavirus and Brucella abortus were detected in 14.7% and 8.98%, respectively, using ELISA technique. Escherichia coli was isolated from diarrheic calf camel (58.2%) 99/170 samples during dry and wet season. Salmonella spp. and Enterococcus spp. were detected in 12% and 8.8% of the specimens, respectively. In this study enterotoxogenic E. coli (ET E. coli) was isolated from 7% of diarrheic camel, which indicates the strong correlation between the camel calf diarrhea and the detection of enterotoxogenic E. coli. This study represented the first report for the detection of group A rotavirus and B. abortus antigen and antibodies in calf camels in Saudi Arabia. It is recommended that the disease should be controlled by vaccination in calf camels.",,"['Al-Ruwaili, Meshref A.', 'Khalil, Omer M.', 'Selim, Samy A.']",,,,
,PMC,Th2 signals induce epithelial injury in mice and are compatible with the biliary atresia phenotype,http://dx.doi.org/10.1172/JCI57728,PMC3204839,,,"Biliary atresia (BA) is a destructive cholangiopathy of childhood in which Th1 immunity has been mechanistically linked to the bile duct inflammation and obstruction that culminate in liver injury. Based on reports of decreased Th1 cytokines in some patients and the development of BA in mice lacking CD4(+) T cells, we hypothesized that Th1-independent mechanisms can also activate effector cells and induce BA. Here, we tested this hypothesis using Stat1(–/–) mice, which lack the ability to mount Th1 immune responses. Infection of Stat1(–/–) mice with rhesus rotavirus type A (RRV) on postnatal day 1 induced a prominent Th2 response, duct epithelial injury and obstruction within 7 days, and atresia shortly thereafter. A high degree of phosphorylation of the Th2 transcription factor Stat6 was observed; however, concurrent inactivation of Stat1 and Stat6 in mice did not prevent BA after RRV infection. In contrast, depletion of macrophages or combined loss of Il13 and Stat1 reduced tissue infiltration by lymphocytes and myeloid cells, maintained epithelial integrity, and prevented duct obstruction. In concordance with our mouse model, humans at the time of BA diagnosis exhibited differential hepatic expression of Th2 genes and serum Th2 cytokines. These findings demonstrate compatibility between Th2 commitment and the pathogenesis of BA, and suggest that patient subgrouping in future clinical trials should account for differences in Th2 status.",,"['Li, Jun', 'Bessho, Kazuhiko', 'Shivakumar, Pranavkumar', 'Mourya, Reena', 'Mohanty, Sujit Kumar', 'dos Santos, Jorge L.', 'Miura, Irene K.', 'Porta, Gilda', 'Bezerra, Jorge A.']",,,,
,PMC,Detection of Adeno-Associated Virus Viremia in Hematopoietic Cell Transplant Recipients,http://dx.doi.org/10.1093/infdis/jir655,PMC3203237,,,"Adeno-associated virus (AAV) is widely considered to be nonpathogenic, but the clinical epidemiology of this virus is limited. By use of polymerase chain reaction assays, we investigated the incidence and clinical significance of AAV viremia in a population of consecutive recipients of a hematopoietic cell transplant (HCT). Four (2.8%) of 145 patients developed AAV viremia after HCT. Viremia was low level and transient in all patients. Two patients were admitted to the hospital and died in proximity to AAV viremia (<7 weeks between diagnosis and death); however, AAV was not detected in tissue specimens obtained at autopsy. Thus, AAV does not appear to play a pathogenic role in organ-specific illness, even in a highly immunocompromised population.",,"['Heugel, Judson', 'Boeckh, Michael', 'Huang, Meei-Li', 'Dierks, Becky', 'Hackman, Robert', 'Fredricks, David', 'Kuypers, Jane', 'Corey, Lawrence']",,,,
,PMC,Digital Dashboard Design Using Multiple Data Streams for Disease Surveillance With Influenza Surveillance as an Example,http://dx.doi.org/10.2196/jmir.1658,PMC3222192,22001082,CC BY,"BACKGROUND: Great strides have been made exploring and exploiting new and different sources of disease surveillance data and developing robust statistical methods for analyzing the collected data. However, there has been less research in the area of dissemination. Proper dissemination of surveillance data can facilitate the end user's taking of appropriate actions, thus maximizing the utility of effort taken from upstream of the surveillance-to-action loop. OBJECTIVE: The aims of the study were to develop a generic framework for a digital dashboard incorporating features of efficient dashboard design and to demonstrate this framework by specific application to influenza surveillance in Hong Kong. METHODS: Based on the merits of the national websites and principles of efficient dashboard design, we designed an automated influenza surveillance digital dashboard as a demonstration of efficient dissemination of surveillance data. We developed the system to synthesize and display multiple sources of influenza surveillance data streams in the dashboard. Different algorithms can be implemented in the dashboard for incorporating all surveillance data streams to describe the overall influenza activity. RESULTS: We designed and implemented an influenza surveillance dashboard that utilized self-explanatory figures to display multiple surveillance data streams in panels. Indicators for individual data streams as well as for overall influenza activity were summarized in the main page, which can be read at a glance. Data retrieval function was also incorporated to allow data sharing in standard format. CONCLUSIONS: The influenza surveillance dashboard serves as a template to illustrate the efficient synthesization and dissemination of multiple-source surveillance data, which may also be applied to other diseases. Surveillance data from multiple sources can be disseminated efficiently using a dashboard design that facilitates the translation of surveillance information to public health actions.",2011 Oct 14,"['Cheng, Calvin KY', 'Ip, Dennis KM', 'Cowling, Benjamin J', 'Ho, Lai Ming', 'Leung, Gabriel M', 'Lau, Eric HY']",J Med Internet Res,,,
,PMC,Evaluation of the Human Host Range of Bovine and Porcine Viruses that may Contaminate Bovine Serum and Porcine Trypsin Used in the Manufacture of Biological Products,http://dx.doi.org/10.1016/j.biologicals.2011.08.003,PMC3206158,,,"Current U.S. requirements for testing cell substrates used in production of human biological products for contamination with bovine and porcine viruses are U.S. Department of Agriculture (USDA) 9CFR tests for bovine serum or porcine trypsin. 9CFR requires testing of bovine serum for seven specific viruses in six families (immunofluorescence) and at least 2 additional families non-specifically (cytopathicity and hemadsorption). 9CFR testing of porcine trypsin is for porcine parvovirus. Recent contaminations suggest these tests may not be sufficient. Assay sensitivity was not the issue for these contaminations that were caused by viruses/virus families not represented in the 9CFR screen. A detailed literature search was undertaken to determine which viruses that infect cattle or swine or bovine or porcine cells in culture also have human host range [ability to infect humans or human cells in culture] and to predict their detection by the currently used 9CFR procedures. There are more viruses of potential risk to biological products manufactured using bovine or porcine raw materials than are likely to be detected by 9CFR testing procedures; even within families, not all members would necessarily be detected. Testing gaps and alternative methodologies should be evaluated to continue to ensure safe, high quality human biologicals.",,"['Marcus-Sekura, Carol', 'Richardson, James C.', 'Harston, Rebecca K.', 'Sane, Nandini', 'Sheets, Rebecca L.']",,,,
,PMC,Toxoplasma gondii HLA-B*0702 restricted GRA7(20–28) peptide with adjuvants and an universal helper T cell epitope elicits CD8(+) T cells producing IFN-γ and reduces parasite burden in HLA-B*0702 mice,http://dx.doi.org/10.1016/j.humimm.2011.10.006,PMC3246109,,,"Ability of CD8(+) T cells to act as cytolytic effectors and produce IFN-γ was shown to mediate resistance to Toxoplasma gondii in murine models due to recognition of peptides restricted by murine MHC Class I molecules. However, no T. gondii specific HLA-B07 restricted peptides were proven protective against T gondii. Recently, two T gondii-specific HLA-B*0702-restricted T cell epitopes, GRA7(20–28) (LPQFATAAT) and GRA3(27–35) (VPFVVFLVA), displayed high-affinity binding to HLA-B*0702, and elicited IFN-γ from PBMCs of seropositive HLA-B*0702 persons. Herein, these peptides were evaluated to determine whether they could elicit IFN-γ in splenocytes of HLA-B*0702 transgenic mice when administered with adjuvants and protect against subsequent challenge. Peptide-specific IFN-γ producing T cells were identified by ELISPOT and proliferation assays utilizing splenic T lymphocytes from HLA transgenic mice. When HLA-B*0702 mice were immunized with one of the epitopes identified, GRA7(20–28) in conjunction with a universal CD4(+) T cell epitope (PADRE) and adjuvants (CD4(+) T cell adjuvant, GLA-SE, and TLR2 stimulatory Pam(2)Cys for CD8(+) T cells), this immunization induced CD8(+) T cells to produce IFN-γ and protected mice against high parasite burden when challenged with T gondii. This work demonstrates feasibility of bioinformatics followed by an empirical approach based on HLA binding to test this biological activity for identifying protective HLA-B*0702 restricted T gondii peptides and adjuvants that elicit protective immune responses in HLA-B*0702 mice.",,"['Cong, Hua', 'Mui, Ernest J.', 'Witola, William H.', 'Sidney, John', 'Alexander, Jeff', 'Sette, Alessandro', 'Maewal, Ajesh', 'El Bissati, Kamal', 'Zhou, Ying', 'Suzuki, Yasuhiro', 'Lee, Daniel', 'Woods, Stuart', 'Sommerville, Caroline', 'Henriquez, Fiona', 'W.Roberts, Craig', 'McLeod, Rima']",,,,
,PMC,"Capturing a Fusion Intermediate of Influenza Hemagglutinin with a Cholesterol-conjugated Peptide, a New Antiviral Strategy for Influenza Virus",http://dx.doi.org/10.1074/jbc.M111.254243,PMC3234914,,,"We previously described fusion-inhibitory peptides that are targeted to the cell membrane by cholesterol conjugation and potently inhibit enveloped viruses that fuse at the cell surface, including HIV, parainfluenza, and henipaviruses. However, for viruses that fuse inside of intracellular compartments, fusion-inhibitory peptides have exhibited very low antiviral activity. We propose that for these viruses, too, membrane targeting via cholesterol conjugation may yield potent compounds. Here we compare the activity of fusion-inhibitory peptides derived from the influenza hemagglutinin (HA) and show that although the unconjugated peptides are inactive, the cholesterol-conjugated compounds are effective inhibitors of infectivity and membrane fusion. We hypothesize that the cholesterol moiety, by localizing the peptides to the target cell membrane, allows the peptides to follow the virus to the intracellular site of fusion. The cholesterol-conjugated peptides trap HA in a transient intermediate state after fusion is triggered but before completion of the refolding steps that drive the merging of the viral and cellular membranes. These results provide proof of concept for an antiviral strategy that is applicable to intracellularly fusing viruses, including known and emerging viral pathogens.",,"['Lee, Kelly K.', 'Pessi, Antonello', 'Gui, Long', 'Santoprete, Alessia', 'Talekar, Aparna', 'Moscona, Anne', 'Porotto, Matteo']",,,,
,PMC,Comparison of Humoral Immune Responses to Epstein-Barr Virus and Kaposi’s Sarcoma–Associated Herpesvirus Using a Viral Proteome Microarray,http://dx.doi.org/10.1093/infdis/jir645,PMC3203236,,,"Background. Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, and Kaposi’s sarcoma–associated herpesvirus (KSHV) has a restricted seroprevalence. Both viruses are associated with malignancies that have an increased frequency in individuals who are coinfected with human immunodeficiency virus type 1 (HIV-1). Methods. To obtain an overview of humoral immune responses to these viruses, we generated a protein array that displayed 174 EBV and KSHV polypeptides purified from yeast. Antibody responses to EBV and KSHV were examined in plasma from healthy volunteers and patients with B cell lymphoma or with AIDS-related Kaposi’s sarcoma or lymphoma. Results. In addition to the commonly studied antigens, IgG responses were frequently detected to the tegument proteins KSHV ORF38 and EBV BBRF and BGLF2 and BNRF1 and to the EBV early lytic proteins BRRF1 and BORF2. The EBV vIL-10 protein was particularly well recognized by plasma IgA. The most intense IgG responses to EBV antigens occurred in HIV-1–positive patients. No clear correlation was observed between viral DNA load in plasma and antibody profile. Conclusions. The protein array provided a sensitive platform for global screening; identified new, frequently recognized viral antigens; and revealed a broader humoral response to EBV compared with KSHV in the same patients.",,"['Zheng, Dasheng', 'Wan, Jun', 'Cho, Yong Gu', 'Wang, Leyao', 'Chiou, Chuang-Jiun', 'Pai, Shweta', 'Woodard, Crystal', 'Zhu, Jian', 'Liao, Gangling', 'Martinez-Maza, Otoniel', 'Qian, Jiang', 'Zhu, Heng', 'Hayward, Gary S.', 'Ambinder, Richard F.', 'Hayward, S. Diane']",,,,
,PMC,Virus-driven conditional expression of an interferon antagonist as a tool to circumvent host restriction,http://dx.doi.org/10.1073/pnas.1114431108,PMC3198330,,,,,"Gerlier, Denis",,,,
,PMC,Amiodarone Exposure During Modest Inflammation Induces Idiosyncrasy-like Liver Injury in Rats: Role of Tumor Necrosis Factor-alpha,http://dx.doi.org/10.1093/toxsci/kfr266,PMC3243747,,,"Amiodarone [2-butyl-3-(3′,5′-diiodo-4’α-diethylaminoethoxybenzoyl)-benzofuran] (AMD), a class III antiarrhythmic drug, is known to cause idiosyncratic hepatotoxic reactions in human patients. One hypothesis for the etiology of idiosyncratic adverse drug reactions is that a concurrent inflammatory stress results in decreased threshold for drug toxicity. To explore this hypothesis in an animal model, male Sprague-Dawley rats were treated with nonhepatotoxic doses of AMD or its vehicle and with saline vehicle or lipopolysaccharide (LPS) to induce low-level inflammation. Elevated alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase activities as well as increased total bile acid concentrations in serum and midzonal hepatocellular necrosis were observed only in AMD/LPS-cotreated rats. The time interval between AMD and LPS administration was critical: AMD injected 16 h before LPS led to liver injury, whereas AMD injected 2–12 h before LPS failed to cause this response. The increase in ALT activity in AMD/LPS cotreatment showed a clear dose-response relationship with AMD as well as LPS. The metabolism and hepatic accumulation of AMD were not affected by LPS coexposure. Serum concentration of tumor necrosis factor-alpha (TNF) was significantly increased by LPS and was slightly prolonged by AMD. In Hepac1c7 cells, addition of TNF potentiated the cytotoxicity of both AMD and its primary metabolite, mono-N-desethylamiodarone. In vivo inhibition of TNF signaling by etanercept attenuated the AMD/LPS-induced liver injury in rats. In summary, AMD treatment during modest inflammation induced severe hepatotoxicity in rats, and TNF contributed to the induction of liver injury in this animal model of idiosyncratic AMD-induced liver injury.",,"['Lu, Jingtao', 'Jones, A. Daniel', 'Harkema, Jack R.', 'Roth, Robert A.', 'Ganey, Patricia E.']",,,,
,PMC,Deconstructing host-pathogen interactions in Drosophila,http://dx.doi.org/10.1242/dmm.000406,PMC3255543,21979942,CC BY-NC-SA,"Many of the cellular mechanisms underlying host responses to pathogens have been well conserved during evolution. As a result, Drosophila can be used to deconstruct many of the key events in host-pathogen interactions by using a wealth of well-developed molecular and genetic tools. In this review, we aim to emphasize the great leverage provided by the suite of genomic and classical genetic approaches available in flies for decoding details of host-pathogen interactions; these findings can then be applied to studies in higher organisms. We first briefly summarize the general strategies by which Drosophila resists and responds to pathogens. We then focus on how recently developed genome-wide RNA interference (RNAi) screens conducted in cells and flies, combined with classical genetic methods, have provided molecular insight into host-pathogen interactions, covering examples of bacteria, fungi and viruses. Finally, we discuss novel strategies for how flies can be used as a tool to examine how specific isolated virulence factors act on an intact host.",2012 Jan 6,"['Bier, Ethan', 'Guichard, Annabel']",Dis Model Mech,,,
,PMC,Development of an improved methodology to detect infectious airborne influenza virus using the NIOSH bioaerosol sampler,http://dx.doi.org/10.1039/c1em10607d,PMC4820822,,,"A unique two-stage cyclone bioaerosol sampler has been developed at NIOSH that can separate aerosols into three size fractions. The ability of this sampler to collect infectious airborne viruses from a calm-air chamber loaded with influenza A virus was tested. The sampler’s efficiency at collecting aerosolized viral particles from a calm-air chamber is essentially the same as that from the high performance SKC BioSampler that collects un-fractionated particles directly into a liquid media (2.4 × 10(4) total viral particles per liter of sampled air (TVP/L) versus 2.6 × 10(4) TVP/L, respectively, after 15 min) and the efficiency is relatively constant over collection times of 15, 30 and 60 min. Approximately 34% of the aerosolized infectious virus collected after 15 min with the NIOSH bioaerosol sampler remained infectious, and infectious virus was found in all three size fractions. After 60 min of sampling, the infectious virus/liter air found in the NIOSH bioaerosol sampler was 15% of that found in the SKC BioSampler. This preservation of infectivity by the NIOSH bioaerosol sampler was maintained even when the initial infectivity prior to aerosolization was as low as 0.06%. The utility of the NIOSH bioaerosol sampler was further extended by incorporating an enhanced infectivity detection methodology developed in our laboratory, the viral replication assay, which amplified the infectious virus making it more readily detectable.",,"['Cao, G.', 'Noti, J. D.', 'Blachere, F. M.', 'Lindsley, W. G.', 'Beezhold, D. H.']",,,,
,PMC,"Incidence of influenza-like illness and severe acute respiratory infection during three influenza seasons in Bangladesh, 2008–2010",http://dx.doi.org/10.2471/BLT.11.090209,PMC3260571,,,"OBJECTIVE: To determine how much influenza contributes to severe acute respiratory illness (SARI), a leading cause of death in children, among people of all ages in Bangladesh. METHODS: Physicians obtained nasal and throat swabs to test for influenza virus from patients who were hospitalized within 7 days of the onset of severe acute respiratory infection (SARI) or who consulted as outpatients for influenza-like illness (ILI). A community health care utilization survey was conducted to determine the proportion of hospital catchment area residents who sought care at study hospitals and calculate the incidence of influenza using this denominator. FINDINGS: The estimated incidence of SARI associated with influenza in children < 5 years old was 6.7 (95% confidence interval, CI: 0–18.3); 4.4 (95% CI: 0–13.4) and 6.5 per 1000 person–years (95% CI: 0–8.3/1000) during the 2008, 2009 and 2010 influenza seasons, respectively. The incidence of SARI in people aged ≥ 5 years was 1.1 (95% CI: 0.4–2.0) and 1.3 (95% CI: 0.5–2.2) per 10 000 person–years during 2009 and 2010, respectively. The incidence of medically attended, laboratory-confirmed seasonal influenza in outpatients with ILI was 10 (95% CI: 8–14), 6.6 (95% CI: 5–9) and 17 per 100 person–years (95% CI: 13–22) during the 2008, 2009 and 2010 influenza seasons, respectively. CONCLUSION: Influenza-like illness is a frequent cause of consultation in the outpatient setting in Bangladesh. Children aged less than 5 years are hospitalized for influenza in greater proportions than children in other age groups.",,"['Azziz-Baumgartner, Eduardo', 'Alamgir, ASM', 'Rahman, Mustafizur', 'Homaira, Nusrat', 'Sohel, Badrul Munir', 'Sharker, MA Yushuf', 'Zaman, Rashid Uz', 'Dee, Jacob', 'Gurley, Emily S', 'Al Mamun, Abdullah', 'Mah-E-Muneer, Syeda', 'Fry, Alicia M', 'Widdowson, Marc-Alain', 'Bresee, Joseph', 'Lindstrom, Stephen', 'Azim, Tasnim', 'Brooks, Abdullah', 'Podder, Goutam', 'Hossain, M Jahangir', 'Rahman, Mahmudur', 'Luby, Stephen P']",,,,
,PMC,"Uptake, Efficacy, and Systemic Distribution of Naked, Inhaled Short Interfering RNA (siRNA) and Locked Nucleic Acid (LNA) Antisense",http://dx.doi.org/10.1038/mt.2011.206,PMC3242665,,,"Antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) promise specific correction of disease-causing gene expression. Therapeutic implementation, however, has been forestalled by poor delivery to the appropriate tissue, cell type, and subcellular compartment. Topical administration is considered to circumvent these issues. The availability of inhalation devices and unmet medical need in lung disease has focused efforts in this tissue. We report the development of a novel cell sorting method for quantitative, cell type-specific analysis of siRNA, and locked nucleic acid (LNA) ASO uptake and efficacy after intratracheal (i.t.) administration in mice. Through fluorescent dye labeling, we compare the utility of this approach to whole animal and whole tissue analysis, and examine the extent of tissue distribution. We detail rapid systemic access and renal clearance for both therapeutic classes and lack of efficacy at the protein level in lung macrophages, epithelia, or other cell types. We nevertheless observe efficient redirection of i.t. administered phosphorothioate (PS) LNA ASO to the liver and kidney leading to targeted gene knockdown. These data suggest delivery remains a key obstacle to topically administered, naked oligonucleotide efficacy in the lung and introduce inhalation as a potentially viable alternative to injection for antisense administration to the liver and kidneys.",,"['Moschos, Sterghios A', 'Frick, Manfred', 'Taylor, Bruce', 'Turnpenny, Paul', 'Graves, Helen', 'Spink, Karen G', 'Brady, Kevin', 'Lamb, David', 'Collins, David', 'Rockel, Thomas D', 'Weber, Markus', 'Lazari, Ovadia', 'Perez-Tosar, Luis', 'Fancy, Sally A', 'Lapthorn, Chris', 'Green, Martin X', 'Evans, Steve', 'Selby, Matthew', 'Jones, Gareth', 'Jones, Lyn', 'Kearney, Sarah', 'Mechiche, Houria', 'Gikunju, Diana', 'Subramanian, Romesh', 'Uhlmann, Eugen', 'Jurk, Marion', 'Vollmer, Jörg', 'Ciaramella, Giuseppe', 'Yeadon, Michael']",,,,
,PMC,Another Look at the Human Papillomavirus Vaccine Experience in Canada,http://dx.doi.org/10.2105/AJPH.2011.300205,PMC3222351,,,"Policy debates about immunization frequently focus on classic trade-offs between individual versus collective well-being. Publicly funded immunization programs are usually justified on the basis of widespread public benefit with minimal individual risk. We discuss the example of the policy process surrounding the adoption of the human papillomavirus (HPV) vaccine in Canada to consider whether public good arguments continue to dominate immunization policymaking. Specifically, we show how a range of stakeholders framed HPV vaccination as a personal—rather than a public—matter, despite the absence of a controversy over mandatory immunization as was the case in the United States. Our findings suggest an erosion of the persuasiveness of public good arguments around collective immunization programs in the policy discourse.",,"['Mah, Catherine L.', 'Deber, Raisa B.', 'Guttmann, Astrid', 'McGeer, Allison', 'Krahn, Murray']",,,,
,PMC,"Informational Privacy, Public Health, and State Laws",http://dx.doi.org/10.2105/AJPH.2011.300206,PMC3222345,,,"Developments in information technology that make it possible to rapidly transmit health information also raise questions about the possible inappropriate use and protection of identifiable (or potentially identifiable) personal health information. Despite efforts to improve state laws, adoption of provisions has lagged. We found that half of states have no statutes addressing nondisclosure of personally identifiable health information generally held by public health agencies. Exceptional treatment of HIV, sexually transmitted infections, or tuberculosis-related information was common. Where other provisions were found, there was little consistency in the laws across states. The variation in state laws supports the need to build consensus on the appropriate use and disclosure of public health information among public health practitioners.",,"[""O'Connor, Jean"", 'Matthews, Gene']",,,,
,PMC,Development of Peptide-Conjugated Morpholino Oligomers as Pan-Arenavirus Inhibitors,http://dx.doi.org/10.1128/AAC.00650-11,PMC3186971,,,"Members of the Arenaviridae family are a threat to public health and can cause meningitis and hemorrhagic fever, and yet treatment options remain limited by a lack of effective antivirals. In this study, we found that peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) complementary to viral genomic RNA were effective in reducing arenavirus replication in cell cultures and in vivo. PPMO complementary to the Junín virus genome were designed to interfere with viral RNA synthesis or translation or both. However, only PPMO designed to potentially interfere with translation were effective in reducing virus replication. PPMO complementary to sequences that are highly conserved across the arenaviruses and located at the 5′ termini of both genomic segments were effective against Junín virus, Tacaribe virus, Pichinde virus, and lymphocytic choriomeningitis virus (LCMV)-infected cell cultures and suppressed viral titers in the livers of LCMV-infected mice. These results suggest that arenavirus 5′ genomic termini represent promising targets for pan-arenavirus antiviral therapeutic development.",,"['Neuman, Benjamin W.', 'Bederka, Lydia H.', 'Stein, David A.', 'Ting, Joey P. C.', 'Moulton, Hong M.', 'Buchmeier, Michael J.']",,,,
,PMC,Very Small Embryonic-Like Stem Cells: Biology and Therapeutic Potential for Heart Repair,http://dx.doi.org/10.1089/ars.2010.3817,PMC3159118,,,"Very small embryonic-like stem cells (VSELs) represent a population of extremely small nonhematopoietic pluripotent cells that are negative for lineage markers and express Sca-1 in mice and CD133 in humans. Their embryonic-like characteristics include the expression of markers of pluripotency; the ability to give rise to cellular derivatives of all three germ-layers; and the ability to form embryoid-like bodies. Indeed, quiescent VSELs may represent the remnants of epiblast-derived cells in adult organs. After tissue injury, including acute myocardial infarction (MI), bone marrow–derived VSELs are mobilized into the peripheral blood and home to the damaged organ. Given the ability of VSELs to differentiate into cardiomyocytes and endothelial cells, and their ability to secrete various cardioprotective growth factors/cytokines, VSELs may serve as an ideal cellular source for cardiac repair. Consistently, transplantation of VSELs after an acute MI improves left ventricular (LV) structure and function, and these benefits remain stable during long-term follow-up. Although the mechanisms remain under investigation, effects of secreted factors, regeneration of cellular constituents, and stimulation of endogenous stem/progenitors may play combinatorial roles. The purpose of this review is to summarize the current evidence regarding the biologic features of VSELs, and to discuss their potential as cellular substrates for therapeutic cardiac repair. Antioxid. Redox Signal. 15, 1821–1834.",,"['Zuba-Surma, Ewa K.', 'Wojakowski, Wojciech', 'Ratajczak, Mariusz Z.', 'Dawn, Buddhadeb']",,,,
,PMC,Comparison of Surface Sampling Methods for Virus Recovery from Fomites,http://dx.doi.org/10.1128/AEM.05709-11,PMC3187074,,,"The role of fomites in infectious disease transmission relative to other exposure routes is difficult to discern due, in part, to the lack of information on the level and distribution of virus contamination on surfaces. Comparisons of studies intending to fill this gap are difficult because multiple different sampling methods are employed and authors rarely report their method's lower limit of detection. In the present study, we compare a subset of sampling methods identified from a literature review to demonstrate that sampling method significantly influences study outcomes. We then compare a subset of methods identified from the review to determine the most efficient methods for recovering virus from surfaces in a laboratory trial using MS2 bacteriophage as a model virus. Recoveries of infective MS2 and MS2 RNA are determined using both a plaque assay and quantitative reverse transcription-PCR, respectively. We conclude that the method that most effectively recovers virus from nonporous fomites uses polyester-tipped swabs prewetted in either one-quarter-strength Ringer's solution or saline solution. This method recovers a median fraction for infective MS2 of 0.40 and for MS2 RNA of 0.07. Use of the proposed method for virus recovery in future fomite sampling studies would provide opportunities to compare findings across multiple studies.",,"['Julian, Timothy R.', 'Tamayo, Francisco J.', 'Leckie, James O.', 'Boehm, Alexandria B.']",,,,
,PMC,Periparturient infection with bovine viral diarrhea virus type 1 causes hemorrhagic proctocolitis in a cow,,PMC3174514,,,"After 3 cows of a dairy herd had died from severe hemorrhagic diarrhea, a 4th sick cow was transported to the clinic. Blood analyses revealed the complete absence of white blood cells, the presence of a type 1b strain of bovine viral diarrhea virus (BVDV), and seroconversion to BVDV.",,"['Laureyns, Jozef', 'Pardon, Bart', 'Letellier, Carine', 'Deprez, Piet']",,,,
,PMC,Role of Lipids in Virus Replication,http://dx.doi.org/10.1101/cshperspect.a004820,PMC3179339,,,"Viruses intricately interact with and modulate cellular membranes at several stages of their replication, but much less is known about the role of viral lipids compared to proteins and nucleic acids. All animal viruses have to cross membranes for cell entry and exit, which occurs by membrane fusion (in enveloped viruses), by transient local disruption of membrane integrity, or by cell lysis. Furthermore, many viruses interact with cellular membrane compartments during their replication and often induce cytoplasmic membrane structures, in which genome replication and assembly occurs. Recent studies revealed details of membrane interaction, membrane bending, fission, and fusion for a number of viruses and unraveled the lipid composition of raft-dependent and -independent viruses. Alterations of membrane lipid composition can block viral release and entry, and certain lipids act as fusion inhibitors, suggesting a potential as antiviral drugs. Here, we review viral interactions with cellular membranes important for virus entry, cytoplasmic genome replication, and virus egress.",,"['Lorizate, Maier', 'Kräusslich, Hans-Georg']",,,,
,PMC,Chemodiversity in Freshwater and Terrestrial Cyanobacteria – a Source for Drug Discovery,,PMC3244969,,,"Cyanobacteria are considered a promising source for new pharmaceutical lead compounds and a large number of chemically diverse and bioactive metabolites have been obtained from cyanobacteria over the last few decades. This review highlights the structural diversity of natural products from freshwater and terrestrial cyanobacteria. The review is divided into three areas: cytotoxic metabolites, protease inhibitors, and antimicrobial metabolites. The first section discusses the potent cytotoxins cryptophycin and tolytoxin. The second section covers protease inhibitors from freshwater and terrestrial cyanobacteria and is divided in five subsections according to structural class: aeruginosins, cyanopeptolins, microviridins, anabaenopeptins, and microginins. Structure activity relationships are discussed within each protease inhibitor class. The third section, antimicrobial metabolites from freshwater and terrestrial cyanobacteria, is divided by chemical class in three subsections: alkaloids, peptides and terpenoids. These examples emphasize the structural diversity and drug development potential of natural products from freshwater and terrestrial cyanobacteria.",,"['Chlipala, George E.', 'Mo, Shunyan', 'Orjala, Jimmy']",,,,
,PMC,From orphan virus to pathogen: the path to the clinical lab,http://dx.doi.org/10.1016/j.coviro.2011.07.006,PMC3190133,,,"Viral metagenomics has recently yielded numerous previously uncharacterized viral genomes from human and animal samples. We review some of the metagenomics tools and strategies to determine which orphan viruses are likely pathogens. Disease association studies compare viral prevalence in patients with unexplained symptoms versus healthy individuals but require these case and control groups to be closely matched epidemiologically. The development of an antibody response in convalescent serum can temporarily link symptoms with a recent infection. Neutralizing antibody detection require often difficult cell culture virus amplification. Antibody binding assays require proper antigen synthesis and positive control sera to set assay thresholds. High levels of viral genetic diversity within orphan viral groups, frequent co-infections, low or rare pathogenicity, and chronic virus shedding, can all complicate disease association studies. The limited availability of matched cases and controls sample sets from different age groups and geographic origins is a major block for estimating the pathogenic potential of recently characterized orphan viruses. Current limitations on the practical use of deep sequencing for viral diagnostics are listed.",,"['Li, Linlin', 'Delwart, Eric']",,,,
,PMC,Synthetic double-stranded RNA enhances airway inflammation and remodelling in a rat model of asthma,http://dx.doi.org/10.1111/j.1365-2567.2011.03473.x,PMC3194222,,,"Respiratory viral infections are frequently associated with exacerbations of asthma. Double-stranded RNA (dsRNA) produced during viral infections may be one of the stimuli for exacerbation. We aimed to assess the potential effect of dsRNA on certain aspects of chronic asthma through the administration of polyinosine-polycytidylic acid (poly I:C), synthetic dsRNA, to a rat model of asthma. Brown Norway rats were sensitized to ovalbumin and challenged three times to evoke airway remodelling. The effect of poly I:C on the ovalbumin-induced airway inflammation and structural changes was assessed from bronchoalveolar lavage fluid and histological findings. The expression of cytokines and chemokines was evaluated by real-time quantitative reverse transcription PCR and ELISA. Ovalbumin-challenged animals showed an increased number of total cells and eosinophils in bronchoalveolar lavage fluid compared with PBS-challenged controls. Ovalbumin-challenged animals treated with poly I:C showed an increased number of total cells and neutrophils in bronchoalveolar lavage fluid compared with those without poly I:C treatment. Ovalbumin-challenged animals showed goblet cell hyperplasia, increased airway smooth muscle mass, and proliferation of both airway epithelial cells and airway smooth muscle cells. Treatment with poly I:C enhanced these structural changes. Among the cytokines and chemokines examined, the expression of interleukins 12 and 17 and of transforming growth factor-β(1) in ovalbumin-challenged animals treated with poly I:C was significantly increased compared with those of the other groups. Double-stranded RNA enhanced airway inflammation and remodelling in a rat model of bronchial asthma. These observations suggest that viral infections may promote airway remodelling.",,"['Takayama, Satoshi', 'Tamaoka, Meiyo', 'Takayama, Koji', 'Okayasu, Kaori', 'Tsuchiya, Kimitake', 'Miyazaki, Yasunari', 'Sumi, Yuki', 'Martin, James G', 'Inase, Naohiko']",,,,
,PMC,A Study of the Genetic Variability of Human Respiratory Syncytial Virus (HRSV) in Cambodia Reveals the Existence of a New HRSV Group B Genotype,http://dx.doi.org/10.1128/JCM.01131-11,PMC3187327,,,"Human respiratory syncytial virus (HRSV) is the leading cause of hospitalization of children aged <5 years due to respiratory illness in industrialized countries, and pneumonia is the leading cause of mortality among children aged <5 years worldwide. Although HRSV was first identified in 1956, a preventative vaccine has yet to be developed. Here we report the results of the first study to investigate the circulation and genetic diversity of HRSV in Cambodia among an all-ages population over 5 consecutive years. The incidences of HRSV infection among all-ages outpatient and hospitalized populations were equivalent, at 9.5% and 8.2%, respectively. Infection was most prevalent among children aged <5 years, with bronchiolitis being the most frequently observed clinical syndrome in the same age group. Circulation of HRSV was seasonal, typically coinciding with the rainy season between July and November annually. Strains belonging to HRSV groups A and B were detected with equivalent frequencies; however, we observed a potentially biennial shift in the predominant circulating HRSV genotype. The majority of HRSV group B strains belonged to the recently described BA genotype, with the exception of 10 strains classified as belonging to a novel HRSV group B genotype, SAB4, first reported here.",,"['Arnott, Alicia', 'Vong, Sirenda', 'Mardy, Sek', 'Chu, Simon', 'Naughtin, Monica', 'Sovann, Ly', 'Buecher, Carole', 'Beauté, Julien', 'Rith, Sareth', 'Borand, Laurence', 'Asgari, Nima', 'Frutos, Roger', 'Guillard, Bertrand', 'Touch, Sok', 'Deubel, Vincent', 'Buchy, Philippe']",,,,
,PMC,External Quality Assessment for Enterovirus 71 and Coxsackievirus A16 Detection by Reverse Transcription-PCR Using Armored RNA as a Virus Surrogate,http://dx.doi.org/10.1128/JCM.00686-11,PMC3187324,,,"Three armored RNAs (virus-like particles [VLPs]) containing target sequences from enterovirus 71 (EV71) and coxsackievirus A16 (CA16) and a pan-enterovirus (pan-EV) sequence were constructed and used in an external quality assessment (EQA) to determine the performance of laboratories in the detection of EV71 and CA16. The EQA panel, which consisted of 20 samples, including 14 positive samples with different concentrations of EV and either EV71 or CA16 armored RNAs, 2 samples with all 3 armored RNAs, and 4 negative-control samples (NaN(3)-preserved minimal essential medium [MEM] without VLPs), was distributed to 54 laboratories that perform molecular diagnosis of hand, foot, and mouth disease (HFMD) virus infections. A total of 41 data sets from 41 participants were returned; 5 (12.2%) were generated using conventional in-house reverse transcription-PCR (RT-PCR) assays, and 36 (87.8%) were generated using commercial real-time RT-PCR assays. Performance assessments of laboratories differed; 12 (29.3%) showed a need for improvement. Surprisingly, 4 laboratories were unable to detect EV71 RNA in any samples, even those containing the highest concentration of 10(7) IU/ml. Furthermore, the detection sensitivity for EV71 among all laboratories (82.1%) was substantially lower than that for EV (97.4%) or CA16 (95.1%). Overall, the results of the present study indicate that EQA should be performed periodically to help laboratories monitor their ability to detect HFMD viruses and to improve the comparability of results from different laboratories.",,"['Song, Liqiong', 'Sun, Shipeng', 'Li, Bo', 'Pan, Yang', 'Li, Wenli', 'Zhang, Kuo', 'Li, Jinming']",,,,
,PMC,Evaluation of Two Magnetic-Bead-Based Viral Nucleic Acid Purification Kits and Three Real-Time Reverse Transcription-PCR Reagent Systems in Two TaqMan Assays for Equine Arteritis Virus Detection in Semen,http://dx.doi.org/10.1128/JCM.01187-11,PMC3187312,,,"This study showed that under specifically defined conditions with respect to nucleic acid extraction method and testing reagents, a previously described real-time reverse transcription-PCR (rRT-PCR) assay (T1 assay) provides sensitivity equal to or higher than that of virus isolation for the detection of equine arteritis virus in semen.",,"['Miszczak, Fabien', 'Shuck, Kathleen M.', 'Lu, Zhengchun', 'Go, Yun Young', 'Zhang, Jianqiang', 'Sells, Stephen', 'Vabret, Astrid', 'Pronost, Stéphane', 'Fortier, Guillaume', 'Timoney, Peter J.', 'Balasuriya, Udeni B. R.']",,,,
,PMC,Unbiased Parallel Detection of Viral Pathogens in Clinical Samples by Use of a Metagenomic Approach,http://dx.doi.org/10.1128/JCM.00273-11,PMC3187305,,,"Viral infectious diseases represent a major threat to public health and are among the greatest disease burdens worldwide. Rapid and accurate identification of viral agents is crucial for both outbreak control and estimating regional disease burdens. Recently developed metagenomic methods have proven to be powerful tools for simultaneous pathogen detection. Here, we performed a systematic study of the capability of the short-read-based metagenomic approach in the molecular detection of viral pathogens in nasopharyngeal aspirate samples from patients with acute lower respiratory tract infections (n = 16). Using the high-throughput capacity of ultradeep sequencing and a dedicated data interpretation method, we successfully identified seven species of known respiratory viral agents from 15 samples, a result that was consistent with results of conventional PCR assays. We also detected a coinfected case that was missed by regular PCR testing. Using the metagenomic data, 11 draft genomes of the abundantly detected viruses in the samples were reconstructed with 21.84% to 98.53% coverage. Our results show the power of the short-read-based metagenomic approach for accurate and parallel screening of viral pathogens. Although there are some inherent difficulties in applying this approach to clinical samples, including a lack of controls, limited specimen quantity, and high contamination rate, our work will facilitate further application of this unprecedented high-throughput method to clinical samples.",,"['Yang, Jian', 'Yang, Fan', 'Ren, Lili', 'Xiong, Zhaohui', 'Wu, Zhiqiang', 'Dong, Jie', 'Sun, Lilian', 'Zhang, Ting', 'Hu, Yongfeng', 'Du, Jiang', 'Wang, Jianwei', 'Jin, Qi']",,,,
,PMC,"Visual Detection of High-Risk Human Papillomavirus Genotypes 16, 18, 45, 52, and 58 by Loop-Mediated Isothermal Amplification with Hydroxynaphthol Blue Dye",http://dx.doi.org/10.1128/JCM.00930-11,PMC3187293,,,"A simple, rapid, sensitive, qualitative, colorimetric loop-mediated isothermal amplification (LAMP) with hydroxynaphthol blue dye (HNB) was established to detect high-risk human papillomavirus (HPV) genotypes 16, 18, 45, 52, and 58. All initial validation studies with the control DNA proved to be type specific. The colorimetric type-specific LAMP assay could achieve a sensitivity of 10 to 100 copies at 63°C for 65 min, comparable to that of real-time PCR. In order to evaluate the reliability of HPV type-specific LAMP, the assay was further evaluated with HPV DNAs from a panel of 294 clinical specimens whose HPV status was previously determined with a novel one-step typing method with multiplex PCR. The tested panel comprised 108 HPV DNA-negative samples and 186 HPV-DNA-positive samples of 14 genotypes. The results showed that the sensitivity of HPV type-specific LAMP for HPV types 16, 18, 45, 52, and 58 was 100%, 100%, 100%, 100%, and 100%, respectively, and the specificity was 100%, 98.5%, 100%, 98.8%, and 99.2%, respectively, compared with a novel one-step typing method with multiplex PCR. No cross-reactivity with other HPV genotypes was observed. In conclusion, this qualitative and colorimetric LAMP assay has potential usefulness for the rapid screening of HPV genotype 16, 18, 45, 52, and 58 infections, especially in resource-limited hospitals or rural clinics of provincial and municipal regions in China.",,"['Luo, Le', 'Nie, Kai', 'Yang, Meng-Jie', 'Wang, Miao', 'Li, Jin', 'Zhang, Chen', 'Liu, Hong-Tu', 'Ma, Xue-Jun']",,,,
,PMC,Quantitative Analysis of T Cell Receptor Diversity in Clinical Samples of Human Peripheral Blood,http://dx.doi.org/10.1016/j.jim.2011.09.012,PMC3253939,,,"The analysis of T cell receptor diversity provides a clinically relevant and sensitive marker of repertoire loss, gain, or skewing. Spectratyping is a broadly utilized technique to measure global TCR diversity by the analysis of the lengths of CDR3 fragments in each Vβ family. However the common use of large numbers of T cells to obtain a global view of TCR Vβ CDR3 diversity has restricted spectratyping analyses when limited T-cell numbers are available in clinical setting, such as following transplant regimens. We here demonstrate that one hundred thousand T cells are sufficient to obtain a robust, highly reproducible measure of the global TCR Vβ repertoire diversity among twenty Vβ families in human peripheral blood. We also show that use of lower cell number results not in a dwindling of observed diversity but rather in non- reproducible patterns in replicate spectratypes. Finally, we report here a simple to use but sensitive method to quantify repertoire divergence in patient samples by comparison to a standard repertoire profile we generated from fifteen normal donors. We provide examples using this method to statistically evaluate the changes in the global TCR Vβ repertoire diversity that may take place during T subset immune reconstitution after hematopoietic stem cell transplantation or after immune modulating therapies.",,"['Memon, Sarfraz A.', 'Sportès, Claude', 'Flomerfelt, Francis A.', 'Gress, Ronald E.', 'Hakim, Frances T.']",,,,
,PMC,Genetic Variants and Susceptibility to Neurological Complications Following West Nile Virus Infection,http://dx.doi.org/10.1093/infdis/jir493,PMC3203390,,,"To determine genetic factors predisposing to neurological complications following West Nile virus infection, we analyzed a cohort of 560 neuroinvasive case patients and 950 control patients for 13 371 mostly nonsynonymous single-nucleotide polymorphisms (SNPs). The top 3 SNPs on the basis of statistical significance were also in genes of biological plausibility: rs2066786 in RFC1 (replication factor C1) (P = 1.88 × 10(−5); odds ratio [OR], 0.68 [95% confidence interval {CI}, .56–.81]); rs2298771 in SCN1A (sodium channel, neuronal type I α subunit) (P = 5.87 × 10(−5); OR, 1.47 [95% CI, 1.21–1.77]); and rs25651 in ANPEP (ananyl aminopeptidase) (P = 1.44 × 10(−4); OR, 0.69 [95% CI, .56–.83]). Additional genotyping of these SNPs in a separate sample of 264 case patients and 296 control patients resulted in a lack of significance in the replication cohort; joint significance was as follows: rs2066786, P = .0022; rs2298771, P = .005; rs25651, P = .042. Using mostly nonsynonymous variants, we therefore did not identify genetic variants associated with neuroinvasive disease.",,"['Loeb, Mark', 'Eskandarian, Sasha', 'Rupp, Mark', 'Fishman, Neil', 'Gasink, Leanne', 'Patterson, Jan', 'Bramson, Jonathan', 'Hudson, Thomas J', 'Lemire, Mathieu']",,,,
,PMC,The Critical Role of Antigen-Presentation-Induced Cytokine Crosstalk in the Central Nervous System in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis,http://dx.doi.org/10.1089/jir.2011.0052,PMC3189551,,,"Multiple sclerosis (MS) is a debilitating disease of the central nervous system (CNS) that has been extensively studied using the animal model experimental autoimmune encephalomyelitis (EAE). It is believed that CD4(+) T lymphocytes play an important role in the pathogenesis of this disease by mediating the demyelination of neuronal axons via secretion of proinflammatory cytokines resulting in the clinical manifestations. Although a great deal of information has been gained in the last several decades about the cells involved in the inflammatory and disease mediating process, important questions have remained unanswered. It has long been held that initial neuroantigen presentation and T cell activation events occur in the immune periphery and then translocate to the CNS. However, an increasing body of evidence suggests that antigen (Ag) presentation might initiate within the CNS itself. Importantly, it has remained unresolved which antigen presenting cells (APCs) in the CNS are the first to acquire and present neuroantigens during EAE/MS to T cells, and what the conditions are under which this takes place, ie, whether this occurs in the healthy CNS or only during inflammatory conditions and what the related cytokine microenvironment is comprised of. In particular, the central role of interferon-γ as a primary mediator of CNS pathology during EAE has been challenged by the emergence of Th17 cells producing interleukin-17. This review describes our current understanding of potential APCs in the CNS and the contribution of these and other CNS-resident cells to disease pathology. Additionally, we discuss the question of where Ag presentation is initiated and under what conditions neuroantigens are made available to APCs with special emphasis on which cytokines may be important in this process.",,"['Sosa, Rebecca A.', 'Forsthuber, Thomas G.']",,,,
,PMC,TLR7/9 versus TLR3/MDA5 signaling during virus infections and diabetes,http://dx.doi.org/10.1189/jlb.0311166,PMC3177694,,,"IFN-I are pleiotropic cytokines that impact innate and adaptive immune responses. In this article, we discuss TLR7/9 versus TLR3/MDA5 signaling in antiviral responses and diabetes. pDCs are thought to have a critical role in antiviral defense because of their ability to rapidly secrete large amounts of IFN-I through TLR7/9 signaling. A recent study demonstrates that although pDCs are a source of IFN-I in vivo, their overall contribution to viral containment is limited and time-dependent, such that additional cellular sources of IFN-I are required to fully control viral infections. dsRNA sensors, such as TLR3 and MDA5, provide another important trigger for antiviral IFN-I responses, which can be exploited to enhance immune responses to vaccines. In the absence of infection, IFN-I production by pDCs or from signaling through dsRNA sensors has been implicated in the pathogenesis of autoimmune diseases such as diabetes. However, recent data demonstrate that IFN-I production via TLR3 and MDA5 is critical to counter diabetes caused by a virus with preferential tropism for pancreatic β-cells. This highlights the complexity of the host antiviral response and how multiple cellular and molecular components balance protective versus pathological responses.",,"['Swiecki, Melissa', 'McCartney, Stephen A.', 'Wang, Yaming', 'Colonna, Marco']",,,,
,PMC,"Traditional Chinese medicine herbal extracts of Cibotium barometz, Gentiana scabra, Dioscorea batatas, Cassia tora, and Taxillus chinensis inhibit SARS-CoV replication",,PMC3942999,24716104,CC BY-NC-SA,"Development of anti-severe acute respiratory syndrome associated coronavirus (SARS-CoV) agents is pivotal to prevent the reemergence of the life-threatening disease, SARS. In this study, more than 200 extracts from Chinese medicinal herbs were evaluated for anti-SARS-CoV activities using a cell-based assay that measured SARS-CoV-induced cytopathogenic effect (CPE) in vitro on Vero E6 cells. Six herbal extracts, one each from Gentianae Radix (龍膽 lóng dǎn; the dried rhizome of Gentiana scabra), Dioscoreae Rhizoma (山藥 shān yào; the tuber of Dioscorea batatas), Cassiae Semen (決明子 jué míng zǐ; the dried seed of Cassia tora) and Loranthi Ramus (桑寄生 sāng jì shēng; the dried stem, with leaf of Taxillus chinensis) (designated as GSH, DBM, CTH and TCH, respectively), and two from Rhizoma Cibotii (狗脊 gǒu jǐ; the dried rhizome of Cibotium barometz) (designated as CBE and CBM), were found to be potent inhibitors of SARS-CoV at concentrations between 25 and 200 μg/ml. The concentrations of the six extracts needed to inhibit 50% of Vero E6 cell proliferation (CC(50)) and 50% of viral replication (EC(50)) were determined. The resulting selective index values (SI = CC(50)/EC(50)) of the most effective extracts CBE, GSH, DBM, CTH and TCH were > 59.4, > 57.5, > 62.1, > 59.4, and > 92.9, respectively. Among these extracts, CBM and DBM also showed significant inhibition of SARS-CoV 3CL protease activity with IC(50) values of 39 μg/ml and 44 μg/ml, respectively. Our findings suggest that these six herbal extracts may have potential as candidates for future development of anti-SARS therapeutics. Abbreviations SARS, severe acute respiratory syndrome CoV, coronavirus CPE, cytopathogenic effect TCM, traditional Chinese medicine",2011 Oct-Dec,"['Wen, Chih-Chun', 'Shyur, Lie-Fen', 'Jan, Jia-Tsrong', 'Liang, Po-Huang', 'Kuo, Chih-Jung', 'Arulselvan, Palanisamy', 'Wu, Jin-Bin', 'Kuo, Sheng-Chu', 'Yang, Ning-Sun']",J Tradit Complement Med,,,
,PMC,Characterization of the Interaction between Human Respiratory Syncytial Virus and the Cell Cycle in Continuous Cell Culture and Primary Human Airway Epithelial Cells,http://dx.doi.org/10.1128/JVI.05164-11,PMC3196461,,,"Viruses can modify conditions inside cells to make them more favorable for replication and progeny virus production. One way of doing this is through manipulation of the cell cycle, a process that describes the ordered growth and division of cells. Analysis of model cell lines, such as A549 cells and primary airway epithelial cells, infected with human respiratory syncytial virus (HRSV) has shown alteration of the cell cycle during infection, although the signaling events were not clearly understood. In this study, targeted transcriptomic analysis of HRSV-infected primary airway epithelial cells revealed alterations in the abundances of many mRNAs encoding cell cycle-regulatory molecules, including decreases in the D-type cyclins and corresponding cyclin-dependent kinases (CDK4 and CDK6 [CDK4/6]). These alterations were reflected in changes in protein abundance and/or relocalization in HRSV-infected cells; taken together, they were predicted to result in G(0)/G(1) phase arrest. In contrast, there was no change in the abundances of D-type cyclins in A549 cells infected with HRSV. However, the abundance of the G(1)/S phase progression inhibitor p21(WAF1/CIP1) was increased over that in mock-treated cells, and this, again, was predicted to result in G(0)/G(1) phase arrest. The G(0)/G(1) phase arrest in both HRSV-infected primary cells and A549 cells was confirmed using dual-label flow cytometry that accurately measured the different stages of the cell cycle. Comparison of progeny virus production in primary and A549 cells enriched in G(0)/G(1) using a specific CDK4/6 kinase inhibitor with asynchronously replicating cells indicated that this phase of the cell cycle was more efficient for virus production.",,"['Wu, Weining', 'Munday, Diane C.', 'Howell, Gareth', 'Platt, Gareth', 'Barr, John N.', 'Hiscox, Julian A.']",,,,
,PMC,Gamma Interferon Controls Mouse Polyomavirus Infection In Vivo,http://dx.doi.org/10.1128/JVI.00761-11,PMC3196421,,,"Human polyomaviruses are associated with substantial morbidity in immunocompromised patients, including those with HIV/AIDS, recipients of bone marrow and kidney transplants, and individuals receiving immunomodulatory agents for autoimmune and inflammatory diseases. No effective antipolyomavirus agents are currently available, and no host determinants have been identified to predict susceptibility to polyomavirus-associated diseases. Using the mouse polyomavirus (MPyV) infection model, we recently demonstrated that perforin-granzyme exocytosis, tumor necrosis factor alpha (TNF-α), and Fas did not contribute to control of infection or virus-induced tumors. Gamma interferon (IFN-γ) was recently shown to inhibit replication by human BK polyomavirus in primary cultures of renal tubular epithelial cells. In this study, we provide evidence that IFN-γ is an important component of the host defense against MPyV infection and tumorigenesis. In immortalized and primary cells, IFN-γ reduces expression of MPyV proteins and impairs viral replication. Mice deficient for the IFN-γ receptor (IFN-γR(−/−)) maintain higher viral loads during MPyV infection and are susceptible to MPyV-induced tumors; this increased viral load is not associated with a defective MPyV-specific CD8(+) T cell response. Using an acute MPyV infection kidney transplant model, we further show that IFN-γR(−/−) donor kidneys harbor higher MPyV levels than donor kidneys from wild-type mice. Finally, administration of IFN-γ to persistently infected mice significantly reduces MPyV levels in multiple organs, including the kidney, a major reservoir for persistent mouse and human polyomavirus infections. These findings demonstrate that IFN-γ is an antiviral effector molecule for MPyV infection.",,"['Wilson, Jarad J.', 'Lin, Eugene', 'Pack, Christopher D.', 'Frost, Elizabeth L.', 'Hadley, Annette', 'Swimm, Alyson I.', 'Wang, Jun', 'Dong, Ying', 'Breeden, Cynthia P.', 'Kalman, Daniel', 'Newell, Kenneth A.', 'Lukacher, Aron E.']",,,,
,PMC,Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) C-Terminal-Activating Region 3 Contributes to LMP1-Mediated Cellular Migration via Its Interaction with Ubc9,http://dx.doi.org/10.1128/JVI.05035-11,PMC3196420,,,"Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1), the principal viral oncoprotein and a member of the tumor necrosis factor receptor superfamily, is a constitutively active membrane signaling protein that regulates multiple signal transduction pathways via its C-terminal-activating region 1 (CTAR1) and CTAR2, and also the less-studied CTAR3. Because protein sumoylation among other posttranslational modifications may regulate many signaling pathways induced by LMP1, we investigated whether during EBV latency LMP1 regulates sumoylation processes that control cellular activation and cellular responses. By immunoprecipitation experiments, we show that LMP1 interacts with Ubc9, the single reported SUMO-conjugating enzyme. Requirements for LMP1-Ubc9 interactions include enzymatically active Ubc9: expression of inactive Ubc9 (Ubc9 C93S) inhibited the LMP1-Ubc9 interaction. LMP1 CTAR3, but not CTAR1 and CTAR2, participated in the LMP1-Ubc9 interaction, and amino acid sequences found in CTAR3, including the JAK-interacting motif, contributed to this interaction. Furthermore, LMP1 expression coincided with increased sumoylation of cellular proteins, and disruption of the Ubc9-LMP1 CTAR3 interaction almost completely abrogated LMP1-induced protein sumoylation, suggesting that this interaction promotes the sumoylation of downstream targets. Additional consequences of the disruption of the LMP1 CTAR3-Ubc9 interaction revealed effects on cellular migration, a hallmark of oncogenesis. Together, these data demonstrate that LMP1 CTAR3 does in fact function in intracellular signaling and leads to biological effects. We propose that LMP1, by interaction with Ubc9, modulates sumoylation processes, which regulate signal transduction pathways that affect phenotypic changes associated with oncogenesis.",,"['Bentz, Gretchen L.', 'Whitehurst, Christopher B.', 'Pagano, Joseph S.']",,,,
,PMC,"Enterovirus 71 and Coxsackievirus A16 3C Proteases: Binding to Rupintrivir and Their Substrates and Anti-Hand, Foot, and Mouth Disease Virus Drug Design",http://dx.doi.org/10.1128/JVI.00787-11,PMC3196414,,,"Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the major causative agents of hand, foot, and mouth disease (HFMD), which is prevalent in Asia. Thus far, there are no prophylactic or therapeutic measures against HFMD. The 3C proteases from EV71 and CVA16 play important roles in viral replication and are therefore ideal drug targets. By using biochemical, mutational, and structural approaches, we broadly characterized both proteases. A series of high-resolution structures of the free or substrate-bound enzymes were solved. These structures, together with our cleavage specificity assay, well explain the marked substrate preferences of both proteases for particular P4, P1, and P1′ residue types, as well as the relative malleability of the P2 amino acid. More importantly, the complex structures of EV71 and CVA16 3Cs with rupintrivir, a specific human rhinovirus (HRV) 3C protease inhibitor, were solved. These structures reveal a half-closed S2 subsite and a size-reduced S1′ subsite that limit the access of the P1′ group of rupintrivir to both enzymes, explaining the reported low inhibition activity of the compound toward EV71 and CVA16. In conclusion, the detailed characterization of both proteases in this study could direct us to a proposal for rational design of EV71/CVA16 3C inhibitors.",,"['Lu, Guangwen', 'Qi, Jianxun', 'Chen, Zhujun', 'Xu, Xiang', 'Gao, Feng', 'Lin, Daizong', 'Qian, Wangke', 'Liu, Hong', 'Jiang, Hualiang', 'Yan, Jinghua', 'Gao, George F.']",,,,
,PMC,Cell-Type-Specific Type I Interferon Antagonism Influences Organ Tropism of Murine Coronavirus,http://dx.doi.org/10.1128/JVI.05075-11,PMC3196400,,,"Previous studies have demonstrated that mouse hepatitis virus (MHV) hepatotropism is determined largely by postentry events rather than by availability of the viral receptor. In addition, mutation of MHV nonstructural protein 2 (ns2) abrogates the ability of the virus to replicate in the liver and induce hepatitis but does not affect replication in the central nervous system (CNS). Here we show that replication of ns2 mutant viruses is attenuated in bone marrow-derived macrophages (BMM) generated from wild-type (wt) mice but not in L2 fibroblasts, primary astrocytes, or BMM generated from type I interferon receptor-deficient (IFNAR(−/−)) mice. In addition, ns2 mutants are more sensitive than wt virus to pretreatment of BMM, but not L2 fibroblasts or primary astrocytes, with alpha/beta interferon (IFN-α/β). The ns2 mutants induced similar levels of IFN-α/β in wt and IFNAR(−/−) BMM, indicating that ns2 expression has no effect on the induction of IFN but rather that it antagonizes a later step in IFN signaling. Consistent with these in vitro data, the virulence of ns2 mutants increased to near that of wt virus after depletion of macrophages in vivo. These data imply that the ability of MHV to replicate in macrophages is a prerequisite for replication in the liver and induction of hepatitis but not for replication or disease in the CNS, underscoring the importance of IFN signaling in macrophages in vivo for protection of the host from hepatitis. Our results further support the notion that viral tissue tropism is determined in part by postentry events, including the early type I interferon response.",,"['Zhao, Ling', 'Rose, Kristine M.', 'Elliott, Ruth', 'Van Rooijen, Nico', 'Weiss, Susan R.']",,,,
,PMC,Resistance of Human Immunodeficiency Virus Type 1 to a Third-Generation Fusion Inhibitor Requires Multiple Mutations in gp41 and Is Accompanied by a Dramatic Loss of gp41 Function,http://dx.doi.org/10.1128/JVI.05331-11,PMC3187517,,,"HIV-1 entry into target cells requires the fusion of viral and cellular membranes. This process is an attractive target for therapeutic intervention, and a first-generation fusion inhibitor, T20 (Enfuvirtide; Fuzeon), was approved for clinical use in 2003. Second-generation (T1249) and third-generation (T2635) fusion inhibitors with improved stability and potency were developed. Resistance to T20 and T1249 usually requires one or two amino acid changes within the binding site. We studied the in vitro evolution of resistance against T2635. After 6 months of culturing, a multitude of resistance mutations was identified in all gp41 subdomains, but no single mutation provided meaningful T2635 resistance. In contrast, multiple mutations within gp41 were required for resistance, and this was accompanied by a dramatic loss of viral infectivity. Because most of the escape mutations were situated outside the T2635 binding site, a decrease in drug target affinity cannot account for most of the resistance. T2635 resistance is likely to depend on altered kinetics of six-helix bundle formation, thus limiting the time window for T2635 to interfere with membrane fusion. Interestingly, the loss of virus infectivity caused by T2635 resistance mutations in gp41 was partially compensated for by a mutation at the base of the V3 domain in gp120. Thus, escape from the third-generation HIV-1 fusion inhibitor T2635 is mechanistically distinct from resistance against its predecessors T20 and T1249. It requires the accumulation of multiple mutations in gp41, is accompanied with a dramatic loss of gp41 function, and induces compensatory mutations in gp120.",,"['Eggink, Dirk', 'Bontjer, Ilja', 'Langedijk, Johannes P. M.', 'Berkhout, Ben', 'Sanders, Rogier W.']",,,,
,PMC,Inactivated or Live-Attenuated Bivalent Vaccines That Confer Protection against Rabies and Ebola Viruses,http://dx.doi.org/10.1128/JVI.00558-11,PMC3187516,,,"The search for a safe and efficacious vaccine for Ebola virus continues, as no current vaccine candidate is nearing licensure. We have developed (i) replication-competent, (ii) replication-deficient, and (iii) chemically inactivated rabies virus (RABV) vaccines expressing Zaire Ebola virus (ZEBOV) glycoprotein (GP) by a reverse genetics system based on the SAD B19 RABV wildlife vaccine. ZEBOV GP is efficiently expressed by these vaccine candidates and is incorporated into virions. The vaccine candidates were avirulent after inoculation of adult mice, and viruses with a deletion in the RABV glycoprotein had greatly reduced neurovirulence after intracerebral inoculation in suckling mice. Immunization with live or inactivated RABV vaccines expressing ZEBOV GP induced humoral immunity against each virus and conferred protection from both lethal RABV and EBOV challenge in mice. The bivalent RABV/ZEBOV vaccines described here have several distinct advantages that may speed the development of inactivated vaccines for use in humans and potentially live or inactivated vaccines for use in nonhuman primates at risk of EBOV infection in endemic areas.",,"['Blaney, Joseph E.', 'Wirblich, Christoph', 'Papaneri, Amy B.', 'Johnson, Reed F.', 'Myers, Carey J.', 'Juelich, Terry L.', 'Holbrook, Michael R.', 'Freiberg, Alexander N.', 'Bernbaum, John G.', 'Jahrling, Peter B.', 'Paragas, Jason', 'Schnell, Matthias J.']",,,,
,PMC,Newcastle Disease Virus Expressing Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Induces Strong Mucosal and Serum Antibody Responses in Guinea Pigs,http://dx.doi.org/10.1128/JVI.05050-11,PMC3187513,,,"Human immunodeficiency virus type 1 (HIV-1) is transmitted mainly through mucosal sites. Optimum strategies to elicit both systemic and mucosal immunity are critical for the development of vaccines against HIV-1. We therefore sought to evaluate the induction of systemic and mucosal immune responses by the use of Newcastle disease virus (NDV) as a vaccine vector. We generated a recombinant NDV, designated rLaSota/gp160, expressing the gp160 envelope (Env) protein of HIV-1 from an added gene. The gp160 protein expressed by rLaSota/gp160 virus was detected on an infected cell surface and was incorporated into the NDV virion. Biochemical studies showed that gp160 present in infected cells and in the virion formed a higher-order oligomer that retained recognition by conformationally sensitive monoclonal antibodies. Expression of gp160 did not increase the virulence of recombinant NDV (rNDV) strain LaSota. Guinea pigs were administered rLaSota/gp160 via the intranasal (i.n.) or intramuscular (i.m.) route in different prime-boost combinations. Systemic and mucosal antibody responses specific to the HIV-1 envelope protein were assessed in serum and vaginal washes, respectively. Two or three immunizations via the i.n. or i.m. route induced a more potent systemic and mucosal immune response than a single immunization by either route. Priming by the i.n. route was more immunogenic than by the i.m. route, and the same was true for the boosts. Furthermore, immunization with rLaSota/gp160 by any route or combination of routes induced a Th1-type response, as reflected by the induction of stronger antigen-specific IgG2a than IgG1 antibody responses. Additionally, i.n. immunization elicited a stronger neutralizing serum antibody response to laboratory-adapted HIV-1 strain MN.3. These data illustrate that it is feasible to use NDV as a vaccine vector to elicit potent humoral and mucosal responses to the HIV-1 envelope protein.",,"['Khattar, Sunil K.', 'Samal, Sweety', 'DeVico, Anthony L.', 'Collins, Peter L.', 'Samal, Siba K.']",,,,
,PMC,Anti-Severe Acute Respiratory Syndrome Coronavirus Spike Antibodies Trigger Infection of Human Immune Cells via a pH- and Cysteine Protease-Independent FcγR Pathway,http://dx.doi.org/10.1128/JVI.00671-11,PMC3187504,,,"Public health measures successfully contained outbreaks of the severe acute respiratory syndrome coronavirus (SARS-CoV) infection. However, the precursor of the SARS-CoV remains in its natural bat reservoir, and reemergence of a human-adapted SARS-like coronavirus remains a plausible public health concern. Vaccination is a major strategy for containing resurgence of SARS in humans, and a number of vaccine candidates have been tested in experimental animal models. We previously reported that antibody elicited by a SARS-CoV vaccine candidate based on recombinant full-length Spike-protein trimers potentiated infection of human B cell lines despite eliciting in vivo a neutralizing and protective immune response in rodents. These observations prompted us to investigate the mechanisms underlying antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro. We demonstrate here that anti-Spike immune serum, while inhibiting viral entry in a permissive cell line, potentiated infection of immune cells by SARS-CoV Spike-pseudotyped lentiviral particles, as well as replication-competent SARS coronavirus. Antibody-mediated infection was dependent on Fcγ receptor II but did not use the endosomal/lysosomal pathway utilized by angiotensin I converting enzyme 2 (ACE2), the accepted receptor for SARS-CoV. This suggests that ADE of SARS-CoV utilizes a novel cell entry mechanism into immune cells. Different SARS vaccine candidates elicit sera that differ in their capacity to induce ADE in immune cells despite their comparable potency to neutralize infection in ACE2-bearing cells. Our results suggest a novel mechanism by which SARS-CoV can enter target cells and illustrate the potential pitfalls associated with immunization against it. These findings should prompt further investigations into SARS pathogenesis.",,"['Jaume, Martial', 'Yip, Ming S.', 'Cheung, Chung Y.', 'Leung, Hiu L.', 'Li, Ping H.', 'Kien, Francois', 'Dutry, Isabelle', 'Callendret, Benoît', 'Escriou, Nicolas', 'Altmeyer, Ralf', 'Nal, Beatrice', 'Daëron, Marc', 'Bruzzone, Roberto', 'Peiris, J. S. Malik']",,,,
,PMC,Engineering T Cells Specific for a Dominant Severe Acute Respiratory Syndrome Coronavirus CD8 T Cell Epitope,http://dx.doi.org/10.1128/JVI.05039-11,PMC3187484,,,"Severe acute respiratory syndrome (SARS) is a highly contagious and life threatening disease, with a fatality rate of almost 10%. The etiologic agent is a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), with animal reservoirs found in bats and other wild animals and thus the possibility of reemergence. In this study, we first investigated at 6 years postinfection whether SARS-specific memory T cells persist in SARS-recovered individuals, demonstrating that these subjects still possess polyfunctional SARS-specific memory CD4(+) and CD8(+) T cells. A dominant memory CD8(+) T cell response against SARS-CoV nucleocaspid protein (NP; amino acids 216 to 225) was then defined in SARS-recovered individuals carrying HLA-B*40:01, a HLA-B molecule present in approximately one-quarter of subjects of Asian ethnicities. To reconstitute such a CD8(+) T cell response, we isolated the alpha and beta T cell receptors of the HLA-B*40:01-restricted SARS-specific CD8(+) T cells. Using T cell receptor gene transfer, we generated SARS-specific redirected T cells from the lymphocytes of normal individuals. These engineered CD8(+) T cells displayed avidity and functionality similar to that of natural SARS-specific memory CD8(+) T cells. They were able to degranulate and produce gamma interferon, tumor necrosis factor alpha, and macrophage inflammatory proteins 1α and 1β after antigenic stimulation. Since there is no effective treatment against SARS, these transduced T cells specific for an immunodominant SARS epitope may provide a new avenue for treatment during a SARS outbreak.",,"['Oh, Hsueh-Ling Janice', 'Chia, Adeline', 'Chang, Cynthia Xin Lei', 'Leong, Hoe Nam', 'Ling, Khoon Lin', 'Grotenbreg, Gijsbert M.', 'Gehring, Adam J.', 'Tan, Yee Joo', 'Bertoletti, Antonio']",,,,
,PMC,"Structural Basis for Antiviral Inhibition of the Main Protease, 3C, from Human Enterovirus 93",http://dx.doi.org/10.1128/JVI.05062-11,PMC3187475,,,"Members of the Enterovirus genus of the Picornaviridae family are abundant, with common human pathogens that belong to the rhinovirus (HRV) and enterovirus (EV) species, including diverse echo-, coxsackie- and polioviruses. They cause a wide spectrum of clinical manifestations ranging from asymptomatic to severe diseases with neurological and/or cardiac manifestations. Pandemic outbreaks of EVs may be accompanied by meningitis and/or paralysis and can be fatal. However, no effective prophylaxis or antiviral treatment against most EVs is available. The EV RNA genome directs the synthesis of a single polyprotein that is autocatalytically processed into mature proteins at Gln↓Gly cleavage sites by the 3C protease (3C(pro)), which has narrow, conserved substrate specificity. These cleavages are essential for virus replication, making 3C(pro) an excellent target for antivirus drug development. In this study, we report the first determination of the crystal structure of 3C(pro) from an enterovirus B, EV-93, a recently identified pathogen, alone and in complex with the anti-HRV molecules compound 1 (AG7404) and rupintrivir (AG7088) at resolutions of 1.9, 1.3, and 1.5 Å, respectively. The EV-93 3C(pro) adopts a chymotrypsin-like fold with a canonically configured oxyanion hole and a substrate binding pocket similar to that of rhino-, coxsackie- and poliovirus 3C proteases. We show that compound 1 and rupintrivir are both active against EV-93 in infected cells and inhibit the proteolytic activity of EV-93 3C(pro) in vitro. These results provide a framework for further structure-guided optimization of the tested compounds to produce antiviral drugs against a broad range of EV species.",,"['Costenaro, Lionel', 'Kaczmarska, Zuzanna', 'Arnan, Carme', 'Janowski, Robert', 'Coutard, Bruno', 'Solà, Maria', 'Gorbalenya, Alexander E.', 'Norder, Heléne', 'Canard, Bruno', 'Coll, Miquel']",,,,
,PMC,In Situ Cleavage of Baculovirus Occlusion-Derived Virus Receptor Binding Protein P74 in the Peroral Infectivity Complex,http://dx.doi.org/10.1128/JVI.05110-11,PMC3187474,,,"Proteolytic processing of viral membrane proteins is common among enveloped viruses and facilitates virus entry. The Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) occlusion-derived virus (ODV) protein P74 is part of a complex of essential peroral infectivity factors (PIFs). Here we report that P74 is efficiently cleaved into two fragments of about equal size by an occlusion body (OB) endogenous alkaline protease during ODV release when AcMNPV OBs are derived from larvae. The cleavage is specific for P74, since the other known peroral infectivity factors in the same complex (PIF1, PIF2, and PIF3) were not cleaved under the same conditions. P74 cleavage was not observed in OBs produced in three different insect cell lines, suggesting a larval host origin of the responsible protease. P74 in OBs produced in larvae of two different host species was cleaved into fragments with the same apparent molecular mass, indicating that the virus incorporates a similar alkaline protease from different hosts. Coimmunoprecipitation analysis revealed that the two P74 subunit fragments remain associated with the recently discovered PIF complex. We propose that under in vivo ODV infection conditions, P74 undergoes two sequential cleavage events, the first one being performed by an ODV-associated host alkaline protease and the second carried out by trypsin in the host midgut.",,"['Peng, Ke', 'van Lent, Jan W. M.', 'Vlak, Just M.', 'Hu, Zhihong', 'van Oers, Monique M.']",,,,
,PMC,Antiviral Drugs for Viruses Other Than Human Immunodeficiency Virus,http://dx.doi.org/10.4065/mcp.2011.0309,PMC3184032,,,"Most viral diseases, with the exception of those caused by human immunodeficiency virus, are self-limited illnesses that do not require specific antiviral therapy. The currently available antiviral drugs target 3 main groups of viruses: herpes, hepatitis, and influenza viruses. With the exception of the antisense molecule fomivirsen, all antiherpes drugs inhibit viral replication by serving as competitive substrates for viral DNA polymerase. Drugs for the treatment of influenza inhibit the ion channel M(2) protein or the enzyme neuraminidase. Combination therapy with Interferon-α and ribavirin remains the backbone treatment for chronic hepatitis C; the addition of serine protease inhibitors improves the treatment outcome of patients infected with hepatitis C virus genotype 1. Chronic hepatitis B can be treated with interferon or a combination of nucleos(t)ide analogues. Notably, almost all the nucleos(t) ide analogues for the treatment of chronic hepatitis B possess anti–human immunodeficiency virus properties, and they inhibit replication of hepatitis B virus by serving as competitive substrates for its DNA polymerase. Some antiviral drugs possess multiple potential clinical applications, such as ribavirin for the treatment of chronic hepatitis C and respiratory syncytial virus and cidofovir for the treatment of cytomegalovirus and other DNA viruses. Drug resistance is an emerging threat to the clinical utility of antiviral drugs. The major mechanisms for drug resistance are mutations in the viral DNA polymerase gene or in genes that encode for the viral kinases required for the activation of certain drugs such as acyclovir and ganciclovir. Widespread antiviral resistance has limited the clinical utility of M(2) inhibitors for the prevention and treatment of influenza infections. This article provides an overview of clinically available antiviral drugs for the primary care physician, with a special focus on pharmacology, clinical uses, and adverse effects.",,"Razonable, Raymund R.",,,,
,PMC,Comparison of SARS and NL63 Papain-Like Protease Binding Sites and Binding Site Dynamics: Inhibitor Design Implications,http://dx.doi.org/10.1016/j.jmb.2011.09.030,PMC3397151,,,"The human severe acute respiratory syndrome coronavirus (SARS-CoV) and the NL63 coronaviruses are human respiratory pathogens for which no effective antiviral treatment exists. The papain-like cysteine proteases encoded by the coronavirus (SARS-CoV: PLpro; NL63: PLP1 and PLP2) represent potential targets for antiviral drug development. Three recent inhibitor-bound PLpro structures highlight the role of an extremely flexible six-residue loop in inhibitor binding. The high binding site plasticity is a major challenge in computational drug discovery/design efforts. From conventional molecular dynamics and accelerated molecular dynamics (aMD) simulations, we find that with conventional molecular dynamics simulation, PLpro translationally samples the open and closed conformation of BL2 loop on a picosecond–nanosecond timescale but does not reproduce the peptide bond inversion between loop residues Tyr269 and Gln270 that is observed on inhibitor GRL0617 binding. Only aMD simulation, starting from the closed loop conformation, reproduced the 180° ϕ–Ψ dihedral rotation back to the open loop state. The Tyr–Gln peptide bond inversion appears to involve a progressive conformational change of the full loop, starting at one side, and progressing to the other. We used the SARS-CoV apo X-ray structure to develop a model of the NL63-PLP2 catalytic site. Superimposition of the PLP2 model on the PLpro X-ray structure identifies binding site residues in PLP2 that contribute to the distinct substrate cleavage site specificities between the two proteases. The topological and electrostatic differences between the two protease binding sites also help explain the selectivity of non-covalent PLpro inhibitors.",,"['Chaudhuri, Rima', 'Tang, Sishi', 'Zhao, Guijun', 'Lu, Hui', 'Case, David A.', 'Johnson, Michael E.']",,,,
,PMC,A small nonhuman primate model for filovirus-induced disease,http://dx.doi.org/10.1016/j.virol.2011.08.022,PMC3195836,,,"Ebolavirus and Marburgvirus are members of the filovirus family and induce a fatal hemorrhagic disease in humans and nonhuman primates with 90% case fatality. To develop a small nonhuman primate model for filovirus disease, common marmosets (Callithrix jacchus) were intramuscularly inoculated with wild type Marburgvirus Musoke or Ebolavirus Zaire. The infection resulted in a systemic fatal disease with clinical and morphological features closely resembling human infection. Animals experienced weight loss, fever, high virus titers in tissue, thrombocytopenia, neutrophilia, high liver transaminases and phosphatases and disseminated intravascular coagulation. Evidence of a severe disseminated viral infection characterized principally by multifocal to coalescing hepatic necrosis was seen in EBOV animals. MARV-infected animals displayed only moderate fibrin deposition in the spleen. Lymphoid necrosis and lymphocytic depletion observed in spleen. These findings provide support for the use of the common marmoset as a small nonhuman primate model for filovirus induced hemorrhagic fever.",,"['Carrion, Ricardo', 'Ro, Youngtae', 'Hoosien, Kareema', 'Ticer, Anysha', 'Brasky, Kathy', 'de la Garza, Melissa', 'Mansfield, Keith', 'Patterson, Jean L.']",,,,
,PMC,Activity and Safety of Synthetic Lectins Based on Benzoboroxole-Functionalized Polymers for Inhibition of HIV Entry,http://dx.doi.org/10.1021/mp2002957,PMC3445258,,,"Lectins derived from plant and microbial sources constitute a vital class of entry inhibitors that target the oligomannose residues on the HIV envelope gp120. Despite their potency and specificity, success of lectin-based entry inhibitors may be impeded by issues in regards to economical production, formulation and potential mitogenicity. Therefore, there exists a gap in the HIV therapeutics pipeline that underscores the need for mass producible, synthetic, broad-spectrum, and biocomptabile inhibitors of HIV entry. Here, we present the development of a polymeric synthetic lectin, based on benzoboroxole (BzB), which exhibits weak affinity (~25 M(−1)) for non-reducing sugars, similar to those found on the HIV envelope. High molecular weight BzB-functionalized polymers demonstrated antiviral activity that increased with an increase in ligand density and molecular weight of the polymer construct; revealing that polyvalency improves activity. Polymers showed significant increase in activity from 25 to 75 mol% BzB functionalization with EC(50) of 15 μM and 15 nM, respectively. A further increase in mole functionalization to 90% resulted in an increase of the EC(50) (59 ± 5 nM), likely due to the elongated rigid structure of the polymer chain compelled by electrostatic repulsion between the boronic acid groups. An increase in molecular weight of the polymer at 50 mol% BzB functionalization showed a gradual but significant increase in antiviral activity, with the highest activity seen with the 382 kDa polymer (EC(50) of 1.1 ± 0.5 nM in CEM cells and 11 ± 3 nM in TZM-bl cells). Supplementing the polymer backbone with 10 mol% sulfonic acid not only increased the aqueous solubility of the polymers by at least 50-fold, but also demonstrated a synergistic increase in anti-HIV activity (4.0 ± 1.5 nM in TZM-bl cells), possibly due to electrostatic interactions between the negatively charged polymer backbone and the positively charged V3-loop in the gp120. The benzoboroxole-sulfonic acid copolymers showed no decrease in activity in the presence of a seminal concentration of fructose (p > 0.05). Additionally, the co-polymers exhibit minimal, if any effect on the cellular viability, barrier properties, or cytokine levels in human reconstructed ecto-cervical tissue after 3 days of repeated exposure and did not show pronounced activity against a variety of other RNA and DNA viruses.",,"['Mahalingam, Alamelu', 'Geonnotti, Anthony R.', 'Balzarini, Jan', 'Kiser, Patrick F.']",,,,
,PMC,Japanese Encephalitis Vaccines,http://dx.doi.org/10.4172/2157-2526.S1-002,PMC3486421,,,"Japanese encephalitis (JE) is a significant human health concern in Asia, Indonesia and parts of Australia with more than 3 billion people potentially at risk of infection with Japanese encephalitis virus (JEV), the causative agent of JE. Given the risk to human health and the theoretical potential for JEV use as a bioweapon, the development of safe and effective vaccines to prevent JEV infection is vital for preserving human health. The development of vaccines for JE began in the 1940s with formalin-inactivated mouse brain-derived vaccines. These vaccines have been shown to induce a protective immune response and to be very effective. Mouse brain-derived vaccines were still in use until May 2011 when the last lots of the BIKEN(®) JE-VAX(®) expired. Development of modern JE vaccines utilizes cell culture-derived viruses and improvements in manufacturing processes as well as removal of potential allergens or toxins have significantly improved vaccine safety. China has developed a live-attenuated vaccine that has proven to induce protective immunity following a single inoculation. In addition, a chimeric vaccine virus incorporating the prM and E structural proteins derived from the live-attenuated JE vaccine into the live-attenuated yellow fever 17D vaccine virus backbone is currently in clinical trials. In this article, we provide a summary of JE vaccine development and on-going clinical trials. We also discuss the potential risk of JEV as a bioweapon with a focus on virus sustainability if used as a weapon.",,"['McArthur, Monica A.', 'Holbrook, Michael R.']",,,,
,PMC,Organ-specific features of natural killer cells,http://dx.doi.org/10.1038/nri3065,PMC3620656,,,"Natural killer (NK) cells can be swiftly mobilized by danger signals and are among the earliest arrivals at target organs of disease. However, the role of NK cells in mounting inflammatory responses is often complex and sometimes paradoxical. Here, we examine the divergent phenotypic and functional features of NK cells, as deduced largely from experimental mouse models of pathophysiological responses in the liver, mucosal tissues, uterus, pancreas, joints and brain. Moreover, we discuss how organ-specific factors, the local microenvironment and unique cellular interactions may influence the organ-specific properties of NK cells.",,"['Shi, Fu-Dong', 'Ljunggren, Hans-Gustaf', 'La Cava, Antonio', 'Van Kaer, Luc']",,,,
,PMC,Effectiveness of facemasks to reduce exposure hazards for airborne infections among general populations,http://dx.doi.org/10.1098/rsif.2011.0537,PMC3306645,,,"Facemasks are widely used as a protective measure by general public to prevent inhalation of airborne pathogens including seasonal, swine and other forms of influenza and severe acute respiratory syndrome (SARS), etc. However, scientific data on effectiveness of facemasks in reducing infections in the community are extremely limited and even inconsistent. In this work, two manikins labelled as ‘source’ and ‘susceptible’ were used to measure the protection provided by facemasks under various emission scenarios. The source was modified to generate polydisperse ultrafine particles, whereas the susceptible was modified to mimic a realistic breathing pattern. The facemask was challenged by both pseudo-steady and highly transient emissions generated by an expiratory process where parameters, such as separation distance between manikins, emission velocity and expiratory duration, were controlled and measured systematically. Performances of four different types of facemask fits, varying from ideal to normal wearing practice, were also investigated. Under the pseudo-steady concentration environment, facemask protection was found to be 45 per cent, while under expiratory emissions, protection varied from 33 to 100 per cent. It was also observed that the separation between the source and the manikin was the most influential parameter affecting facemask protection.",,"['Lai, A. C. K.', 'Poon, C. K. M.', 'Cheung, A. C. T.']",,,,
,PMC,Genetic Polymorphisms in Host Antiviral Genes: Associations with Humoral and Cellular Immunity to Measles Vaccine,http://dx.doi.org/10.1016/j.vaccine.2011.09.043,PMC3941984,,,"Host antiviral genes are important regulators of antiviral immunity and plausible genetic determinants of immune response heterogeneity after vaccination. We genotyped and analyzed 307 common candidate tagSNPs from 12 antiviral genes in a cohort of 745 schoolchildren immunized with two doses of measles-mumps-rubella vaccine. Associations between SNPs/haplotypes and measles virus-specific immune outcomes were assessed using linear regression methodologies in Caucasians and African-Americans. Genetic variants within the DDX58/RIG-I gene, including a coding polymorphism (rs3205166/Val800Val), were associated as single-SNPs (p≤0.017; although these SNPs did not remain significant after correction for false discovery rate/FDR) and in haplotype-level analysis, with measles-specific antibody variations in Caucasians (haplotype allele p-value=0.021; haplotype global p-value=0.076). Four DDX58 polymorphisms, in high LD, demonstrated also associations (after correction for FDR) with variations in both measles-specific IFN-γ and IL-2 secretion in Caucasians (p≤0.001, q=0.193). Two intronic OAS1 polymorphisms, including the functional OAS1 SNP rs10774671 (p=0.003), demonstrated evidence of association with a significant allele-dose-related increase in neutralizing antibody levels in African-Americans. Genotype and haplotype-level associations demonstrated the role of ADAR genetic variants, including a non-synonymous SNP (rs2229857/Arg384Lys; p=0.01), in regulating measles virus-specific IFN-γ Elispot responses in Caucasians (haplotype global p-value=0.017). After correction FDR, 15 single-SNP associations (11 SNPs in Caucasians and 4 SNPs in African-Americans) still remained significant at the q-value<0.20. In conclusion, our findings strongly point to genetic variants/genes, involved in antiviral sensing and antiviral control, as critical determinants, differentially modulating the adaptive immune responses to live attenuated measles vaccine in Caucasians and African-Americans.",,"['Haralambieva, Iana H.', 'Ovsyannikova, Inna G.', 'Umlauf, Benjamin J.', 'Vierkant, Robert A.', 'Pankratz, V. Shane', 'Jacobson, Robert M.', 'Poland, Gregory A.']",,,,
,PMC,Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection,http://dx.doi.org/10.1016/j.cell.2011.08.015,PMC3176439,,,"Cytokine storm during viral infection is a prospective predictor of morbidity and mortality, yet the cellular sources remain undefined. Here, using genetic and chemical tools to probe functions of the S1P(1) receptor, we elucidate cellular and signaling mechanisms important in initiating cytokine storm. While S1P(1) receptor is expressed on endothelial cells and lymphocytes within lung tissue, S1P(1) agonism suppresses cytokines and innate immune cell recruitment in wild-type and lymphocyte deficient mice, identifying endothelial cells as central regulators of cytokine storm. Furthermore, our data reveal immune cell infiltration and cytokine production as distinct events both orchestrated by endothelial cells. Moreover, we demonstrate that suppression of early innate immune responses through S1P(1) signaling results in reduced mortality during infection with a human pathogenic strain of influenza virus. Modulation of endothelium with a specific agonist suggests that diseases where amplification of cytokine storm is a significant pathological component could be chemically tractable.",,"['Teijaro, John R.', 'Walsh, Kevin B.', 'Cahalan, Stuart M.', 'Fremgen, Daniel M.', 'Roberts, Edward', 'Scott, Fiona', 'Martinborough, Esther', 'Peach, Robert', 'Oldstone, Michael B.A.', 'Rosen, Hugh']",,,,
,PMC,A Simulation Framework to Investigate in vitro Viral Infection Dynamics,http://dx.doi.org/10.1016/j.jocs.2011.08.007,PMC3652481,,,"Virus infection is a complex biological phenomenon for which in vitro experiments provide a uniquely concise view where data is often obtained from a single population of cells, under controlled environmental conditions. Nonetheless, data interpretation and real understanding of viral dynamics is still hampered by the sheer complexity of the various intertwined spatio-temporal processes. In this paper we present a tool to address these issues: a cellular automata model describing critical aspects of in vitro viral infections taking into account spatial characteristics of virus spreading within a culture well. The aim of the model is to understand the key mechanisms of SARS-CoV infection dynamics during the first 24 hours post infection. Using a simulated annealing algorithm we tune free parameters with data from SARS-CoV infection of cultured lung epithelial cells. We also interrogate the model using a Latin Hypercube sensitivity analysis to identify which mechanisms are critical to the observed infection of host cells and the release of measured virus particles.",,"['Bankhead, Armand', 'Mancini, Emiliano', 'Sims, Amy C.', 'Baric, Ralph S.', 'McWeeney, Shannon', 'Sloot, Peter M.A.']",,,,
,PMC,SARS-CoV heptad repeat 2 is a trimer of parallel helices,http://dx.doi.org/10.1002/pro.736,PMC3302656,,,"In severe acute respiratory syndrome coronavirus, the envelope heptad repeat 2 (HR2) plays a critical role in viral entry. Moreover, HR2 is both the target for novel antiviral therapies and, as an isolated peptide, presents a potential antiviral therapeutic. The structure of HR2, as determined by NMR spectroscopy in the presence of the co-solvent trifluoroethanol (TFE), is a trimer of parallel helices, whereas the structure of HR2, as determined by X-ray crystallography, is a tetramer of anti-parallel helices. In this work, we added a nitroxide spin label to the N-terminal region of HR2 and used paramagnetic relaxation enhancement to assess the orientation of the HR2 helices under different solution conditions. We find that the relaxation effects are consistent with an orientation corresponding to a trimer of parallel helices in both the presence and absence of TFE. This work suggests that the different orientation and oligomerization states observed by NMR and X-ray are due to the 11 additional residues present at the N-terminus of the NMR construct.",,"['Celigoy, Jessica', 'Ramirez, Benjamin', 'Caffrey, Michael']",,,,
,PMC,Coronavirus Infection Induces DNA Replication Stress Partly through Interaction of Its Nonstructural Protein 13 with the p125 Subunit of DNA Polymerase δ,http://dx.doi.org/10.1074/jbc.M111.242206,PMC3234778,,,"Perturbation of cell cycle regulation is a characteristic feature of infection by many DNA and RNA viruses, including Coronavirus infectious bronchitis virus (IBV). IBV infection was shown to induce cell cycle arrest at both S and G(2)/M phases for the enhancement of viral replication and progeny production. However, the underlying mechanisms are not well explored. In this study we show that activation of cellular DNA damage response is one of the mechanisms exploited by Coronavirus to induce cell cycle arrest. An ATR-dependent cellular DNA damage response was shown to be activated by IBV infection. Suppression of the ATR kinase activity by chemical inhibitors and siRNA-mediated knockdown of ATR reduced the IBV-induced ATR signaling and inhibited the replication of IBV. Furthermore, yeast two-hybrid screens and subsequent biochemical and functional studies demonstrated that interaction between Coronavirus nsp13 and DNA polymerase δ induced DNA replication stress in IBV-infected cells. These findings indicate that the ATR signaling activated by IBV replication contributes to the IBV-induced S-phase arrest and is required for efficient IBV replication and progeny production.",,"['Xu, Ling Hui', 'Huang, Mei', 'Fang, Shou Guo', 'Liu, Ding Xiang']",,,,
,PMC,Anticipating the Species Jump: Surveillance for Emerging Viral Threats,http://dx.doi.org/10.1111/j.1863-2378.2011.01439.x,PMC4948863,,,"Zoonotic disease surveillance is typically triggered after animal pathogens have already infected humans. Are there ways to identify high-risk viruses before they emerge in humans? If so, then how and where can identifications be made and by what methods? These were the fundamental questions driving a workshop to examine the future of predictive surveillance for viruses that might jump from animals to infect humans. Virologists, ecologists and computational biologists from academia, federal government and non-governmental organizations discussed opportunities as well as obstacles to the prediction of species jumps using genetic and ecological data from viruses and their hosts, vectors and reservoirs. This workshop marked an important first step towards envisioning both scientific and organizational frameworks for this future capability. Canine parvoviruses as well as seasonal H3N2 and pandemic H1N1 influenza viruses are discussed as exemplars that suggest what to look for in anticipating species jumps. To answer the question of where to look, prospects for discovering emerging viruses among wildlife, bats, rodents, arthropod vectors and occupationally exposed humans are discussed. Finally, opportunities and obstacles are identified and accompanied by suggestions for how to look for species jumps. Taken together, these findings constitute the beginnings of a conceptual framework for achieving a virus surveillance capability that could predict future species jumps.",,"['Flanagan, M. L.', 'Parrish, C. R.', 'Cobey, S.', 'Glass, G. E.', 'Bush, R. M.', 'Leighton, T. J.']",,,,
,PMC,Viruses and Sialic Acids: Rules of Engagement,http://dx.doi.org/10.1016/j.sbi.2011.08.009,PMC3189341,,,"Viral infections are initiated by specific attachment of a virus particle to receptors at the surface of the host cell. For many viruses, these receptors are glycans that are linked to either a protein or a lipid. Glycans terminating in sialic acid and its derivatives serve as receptors for a large number of viruses, including several human pathogens. In combination with glycan array analyses, structural analyses of complexes of viruses with sialylated oligosaccharides have provided insights into the parameters that underlie each interaction. Here, we compare the currently available structural data on viral attachment proteins in complex with sialic acid and its variants. The objective is to define common parameters of recognition and to provide a platform for understanding the determinants of specificity. This information could be of use for the prediction of the location of sialic acid binding sites in viruses for which structural information is still lacking. An improved understanding of the principles that govern the recognition of sialic acid and sialylated oligosaccharides would also advance efforts to develop efficient antiviral agents.",,"['Neu, Ursula', 'Bauer, Johannes', 'Stehle, Thilo']",,,,
,PMC,Autophagy-mediated DC activation is essential for innate cytokine production and APC function with Respiratory Syncytial Virus responses,http://dx.doi.org/10.4049/jimmunol.1100524,PMC3186849,,,"The regulation of innate immune responses during viral infection is a crucial step to promote anti-viralreactions. Recent studies have drawn attention to a strong relationship of pathogen associated molecular patterns (PAMP) recognition with autophagy for activation of APC function. Our initial observations indicated that autophagosomes formed in response to RSV infection of DC. To further investigate whether RSV-induced DC activation and innate cytokine production was associated with autophagy, we utilized several methods to block autophagosome formation. Using 3-MA,siRNA inhibition of LC3,or Beclin +/- mouse derived DC,studies establisheda relationship between RSV-induced autophagy and enhanced type I IFN, TNF, IL-6, and IL-12p40expression. Moreover, autophagosome formation induced by starvation also promoted innate cytokine expression in DC. The induction of starvation-induced autophagy in combination with RSV infection synergistically enhanced DC cytokine expressionthat was blocked by an autophagy inhibitor. The latter synergistic responses were differentially altered in DC from MyD88-/- and TRIF-/-mice supporting the concept of autophagy-mediated TLR signaling. In addition, blockade of autophagy in RSV-infected DC inhibited the maturation of DCs as assessed by MHC Class II and co-stimulatory molecule expression. Subsequently, we demonstrated that inhibition of autophagy in DCsused to stimulateprimary ovalbumin-induced and secondary RSV-infected responses significantly attenuatedcytokine production by CD4+ T cells. Thus, these studies have outlined that autophagy in DC afterRSV infection isa crucial mechanism for driving innate cytokine productionleading to alteredacquired immune responses.",,"['Morris, Susan', 'Swanson, Michele S.', 'Lieberman, Andrew', 'Reed, Michelle', 'Yue, Zhenyu', 'Lindell, Dennis M.', 'Lukacs, Nicholas W.']",,,,
,PMC,Proteomic Analysis of Virus-Host Interactions in an Infectious Context Using Recombinant Viruses,http://dx.doi.org/10.1074/mcp.M110.007443,PMC3237069,,,"RNA viruses exhibit small-sized genomes encoding few proteins, but still establish complex networks of interactions with host cell components to achieve replication and spreading. Ideally, these virus-host protein interactions should be mapped directly in infected cell culture, but such a high standard is often difficult to reach when using conventional approaches. We thus developed a new strategy based on recombinant viruses expressing tagged viral proteins to capture both direct and indirect physical binding partners during infection. As a proof of concept, we engineered a recombinant measles virus (MV) expressing one of its virulence factors, the MV-V protein, with a One-STrEP amino-terminal tag. This allowed virus-host protein complex analysis directly from infected cells by combining modified tandem affinity chromatography and mass spectrometry analysis. Using this approach, we established a prosperous list of 245 cellular proteins interacting either directly or indirectly with MV-V, and including four of the nine already known partners of this viral factor. These interactions were highly specific of MV-V because they were not recovered when the nucleoprotein MV-N, instead of MV-V, was tagged. Besides key components of the antiviral response, cellular proteins from mitochondria, ribosomes, endoplasmic reticulum, protein phosphatase 2A, and histone deacetylase complex were identified for the first time as prominent targets of MV-V and the critical role of the later protein family in MV replication was addressed. Most interestingly, MV-V showed some preferential attachment to essential proteins in the human interactome network, as assessed by centrality and interconnectivity measures. Furthermore, the list of MV-V interactors also showed a massive enrichment for well-known targets of other viruses. Altogether, this clearly supports our approach based on reverse genetics of viruses combined with high-throughput proteomics to probe the interaction network that viruses establish in infected cells.",,"['Komarova, Anastassia V.', 'Combredet, Chantal', 'Meyniel-Schicklin, Laurène', 'Chapelle, Manuel', 'Caignard, Grégory', 'Camadro, Jean-Michel', 'Lotteau, Vincent', 'Vidalain, Pierre-Olivier', 'Tangy, Frédéric']",,,,
,PMC,RNA therapeutics targeting osteoclast-mediated excessive bone resorption,http://dx.doi.org/10.1016/j.addr.2011.09.002,PMC3293106,,,"RNA interference (RNAi) is a sequence-specific post-transcriptional gene silencing technique developed with dramatically increasing utility for both scientific and therapeutic purposes. Short interfering RNA (siRNA) is currently exploited to regulate protein expression relevant to many therapeutic applications, and commonly used as a tool for elucidating disease-associated genes. Osteoporosis and their associated osteoporotic fragility fractures in both men and women are rapidly becoming a global healthcare crisis as average life expectancy increases worldwide. New therapeutics are needed for this increasing patient population. This review describes the diversity of molecular targets suitable for RNAi-based gene knock-down in osteoclasts to control osteoclast-mediated excessive bone resorption. We identify strategies for developing targeted siRNA delivery and efficient gene silencing, and describe opportunities and challenges of introducing siRNA as a therapeutic approach to hard and connective tissue disorders.",,"['Wang, Yuwei', 'Grainger, David W']",,,,
,PMC,Pathological observations of lung inflammation after administration of IP-10 in influenza virus- and respiratory syncytial virus-infected mice,http://dx.doi.org/10.3892/etm.2011.350,PMC3438799,,,Pneumonia is a common complication of influenza virus infection and a common cause of death of patients. The aim of this study was to test the hypothesis that interferon-γ-inducible protein-10 (IP-10) is an important chemokine in the development of airway inflammation caused by certain viruses. Mice were infected with influenza virus after administration of murine IP-10 and the severity of pneumonia was compared with the group which was infected with influenza virus alone. Another mice group was infected with respiratory syncytial virus (RSV) after injection of IP-10 and also the severity of pneumonia was compared to the group which was infected with RSV alone. The mice infected with influenza virus or RSV after administration of IP-10 presented with more fulminant and necrotizing diffuse alveolar and bronchiole damage with lymphocyte infiltration. Our results indicate that IP-10 is an important chemokine and is associated with the severity of pneumonia caused by certain viruses.,,"['LUO, HONG', 'WANG, DONG', 'CHE, HAI-LONG', 'ZHAO, YUE', 'JIN, HONG']",,,,
,PMC,Adventures and lessons of an American biochemist in China,http://dx.doi.org/10.1007/s13238-011-1085-3,PMC4875331,,,,,"Vavricka, Christopher J.",,,,
,PMC,"In vitro and in vivo efficacy of fluorodeoxycytidine analogs against highly pathogenic avian influenza H5N1, seasonal, and pandemic H1N1 virus infections",http://dx.doi.org/10.1016/j.antiviral.2011.09.001,PMC3216401,,,"Various fluorodeoxyribonucleosides were evaluated for their antiviral activities against influenza virus infections in vitro and in vivo. Among the most potent inhibitors was 2'-deoxy-2'-fluorocytidine (2'-FdC). It inhibited various strains of low and highly pathogenic avian influenza H5N1 viruses, pandemic H1N1 viruses, an oseltamivir-resistant pandemic H1N1 virus, and seasonal influenza viruses (H3N2, H1N1, influenza B) in MDCK cells, with the 90% inhibitory concentrations ranging from 0.13 µM to 4.6 µM, as determined by a virus yield reduction assay. 2'-FdC was then tested for efficacy in BALB/c mice infected with a lethal dose of highly pathogenic influenza A/Vietnam/1203/2004 H5N1 virus. 2’FdC (60 mg/kg/d) administered intraperitoneally (i.p.) twice a day beginning 24 h after virus exposure significantly promoted survival (80% survival) of infected mice (p=0.0001). Equally efficacious were the treatment regimens in which mice were treated with 2'-FdC at 30 or 60 mg/kg/day (bid × 8) beginning 24 h before virus exposure. At these doses, 70–80% of the mice were protected from death due to virus infection (p=0.0005, p=0.0001; respectively). The lungs harvested from treated mice at day four of the infection displayed little surface pathology or histopathology, lung weights were lower, and the 60 mg/kg dose reduced lung virus titers, although not significantly compared to the placebo controls. All doses were well tolerated in uninfected mice. 2'-FdC could also be administered as late as 72 h post virus exposure and still significantly protect 60% mice from the lethal effects of the H5N1 virus infection (p=0.019). Other fluorodeoxyribonucleosides tested in the H5N1 mouse model, 2’-deoxy-5-fluorocytidine and 2'-deoxy-2', 2'-difluorocytidine, were very toxic at higher doses and not inhibitory at lower doses. Finally, 2'-FdC, which was active in the H5N1 mouse model, was also active in a pandemic H1N1 influenza A infection model in mice. When given at 30 mg/kg/d (bid × 5) beginning 24 h before virus exposure), 2’-FdC also significantly enhanced survival of H1N1-infected mice (50%, p=0.038) similar to the results obtained in the H5N1 infection model using a similar dosing regimen (50%, p<0.05). Given the demonstrated in vitro and in vivo inhibition of avian influenza virus replication, 2’FdC may qualify as a lead compound for the development of agents treating influenza virus infections.",,"['Kumaki, Yohichi', 'Day, Craig W.', 'Smee, Donald F.', 'Morrey, John D.', 'Barnard, Dale L.']",,,,
,PMC,"Neutralizing Human Monoclonal Antibodies to Severe Acute Respiratory Syndrome Coronavirus: Target, Mechanism of Action and Therapeutic Potential",http://dx.doi.org/10.1002/rmv.706,PMC3256278,,,"The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) led to a rapid response not only to contain the outbreak but also to identify possible therapeutic interventions, including the generation of human monoclonal antibodies (hmAbs). Human mAbs may be used therapeutically without the drawbacks of chimeric or animal Abs. Several different methods have been used to generate SARS-CoV specific neutralizing hmAbs including the immunization of transgenic mice, cloning of small chain variable regions from naïve and convalescent patients, and the immortalization of convalescent B cells. Irrespective of the techniques used, the majority of hmAbs specifically reacted with the receptor binding domain (RBD) of the spike (S) protein and likely prevented receptor binding. However, several hmAbs that can bind to epitopes either within the RBD, located N terminal of the RBD or in the S2 domain and neutralize the virus with or without inhibiting receptor binding have been identified. Therapeutic utility of hmAbs has been further elucidated through the identification of potential combinations of hmAbs that could neutralize viral variants including escape mutants selected using hmAbs. These results suggest that a cocktail of hmAbs which can bind to unique epitopes and have different mechanisms of action might be of clinical utility against SARS-CoV infection, and indicate that a similar approach may be applied to treat other viral infections.",,"['Coughlin, Melissa M.', 'Prabhakar, Bellur S.']",,,,
,PMC,Discovery of Novel Selective Serotonin Reuptake Inhibitors Through Development of a Protein-Based Pharmacophore,http://dx.doi.org/10.1021/ci200280m,PMC3183329,,,"The serotonin transporter (SERT), a member of the neurotransmitter sodium symporter (NSS) family, is responsible for the reuptake of serotonin from the synaptic cleft to maintain neurotransmitter homeostasis. SERT is established as an important target in the treatment of anxiety and depression. Because a high-resolution crystal structure is not available, a computational model of SERT was built based upon the x-ray coordinates of the leucine transporter LeuT, a bacterial NSS homolog. The model was used to develop the first SERT structure-based pharmacophore. Virtual screening (VS) of a small molecule structural library using the generated SERT computational model yielded candidate ligands of diverse scaffolds. Pharmacological analysis of the VS hits identified two SERT-selective compounds, potential lead compounds for further SERT-related medication development.",,"['Manepalli, Sankar', 'Geffert, Laura M.', 'Surratt, Christopher K.', 'Madura, Jeffry D.']",,,,
,PMC,"Peak Oil, Urban Form, and Public Health: Exploring the Connections",http://dx.doi.org/10.2105/AJPH.2011.300192,PMC3154239,,,"We assessed the relationships between peak oil and urban form, travel behavior, and public health. Peak oil will affect the general economy, travel behavior, and urban form through income and substitution effects; however, because of the wide range of substitution possibilities, the impacts are likely to be gradual and relatively small. Furthermore, we suggest that changes in travel behavior and increases in urban density will have both favorable and unfavorable effects on public health. To mitigate the adverse impacts and to maximize the positive effects of peak oil, we recommend that careful attention should be paid to urban design and public health responses for a range of urbanization patterns.",,"['Kaza, Nikhil', 'Knaap, Gerrit-Jan', 'Knaap, Isolde', 'Lewis, Rebecca']",,,,
,PMC,"South-to-North, Cross-Disciplinary Training in Global Health Practice: Ten Years of Lessons Learned from an Infectious Disease Field Course in Jamaica",http://dx.doi.org/10.4269/ajtmh.2011.10-0524,PMC3163856,,,"Global commerce, travel, and emerging and resurging infectious diseases have increased awareness of global health threats and opportunities for collaborative and service learning. We review course materials, knowledge archives, data management archives, and student evaluations for the first 10 years of an intensive summer field course in infectious disease epidemiology and surveillance offered in Jamaica. We have trained 300 students from 28 countries through collaboration between the University of the West Indies and U.S. partner universities. Participants were primarily graduate students in public health, but also included health professionals with terminal degrees, and public health nurses and inspectors. Strong institutional synergies, committed faculty, an emphasis on scientific and cultural competencies, and use of team-based field research projects culminate in a unique training environment that provides participants with career-developing experiences. We share lessons learned over the past decade, and conclude that South-to-North leadership is critical in shaping transdisciplinary, cross-cultural, global health practice.",,"['Scarlett, Henroy P.', 'Nisbett, Richard A.', 'Stoler, Justin', 'Bain, Brendan C.', 'Bhatta, Madhav P.', 'Castle, Trevor', 'Harbertson, Judith', 'Brodine, Stephanie K.', 'Vermund, Sten H.']",,,,
,PMC,Humanized θ-Defensins (Retrocyclins) Enhance Macrophage Performance and Protect Mice from Experimental Anthrax Infections,http://dx.doi.org/10.1128/AAC.00267-11,PMC3165295,,,"Retrocyclins are humanized versions of the θ-defensin peptides expressed by the leukocytes of several nonhuman primates. Previous studies, performed in serum-free media, determined that retrocyclins 1 (RC1) and RC2 could prevent successful germination of Bacillus anthracis spores, kill vegetative B. anthracis cells, and inactivate anthrax lethal factor. We now report that retrocyclins are extensively bound by components of native mouse, human, and fetal calf sera, that heat-inactivated sera show greatly enhanced retrocyclin binding, and that native and (especially) heat-inactivated sera greatly reduce the direct activities of retrocyclins against spores and vegetative cells of B. anthracis. Nevertheless, we also found that retrocyclins protected mice challenged in vivo by subcutaneous, intraperitoneal, or intranasal instillation of B. anthracis spores. Retrocyclin 1 bound extensively to B. anthracis spores and enhanced their phagocytosis and killing by murine RAW264.7 cells. Based on the assumption that spore-bound RC1 enters phagosomes by “piggyback phagocytosis,” model calculations showed that the intraphagosomal concentration of RC1 would greatly exceed its extracellular concentration. Murine alveolar macrophages took up fluorescently labeled retrocyclin, suggesting that macrophages may also acquire extracellular RC1 directly. Overall, these data demonstrate that retrocyclins are effective in vivo against experimental murine anthrax infections and suggest that enhanced macrophage function contributes to this property.",,"['Welkos, S.', 'Cote, C. K.', 'Hahn, U.', 'Shastak, O.', 'Jedermann, J.', 'Bozue, J.', 'Jung, G.', 'Ruchala, P.', 'Pratikhya, P.', 'Tang, T.', 'Lehrer, R. I.', 'Beyer, W.']",,,,
,PMC,Dissimilar Properties of Two Recombinant Lactobacillus acidophilus Strains Displaying Salmonella FliC with Different Anchoring Motifs,http://dx.doi.org/10.1128/AEM.05153-11,PMC3187123,,,"Display of heterologous antigens on the cell surface is considered a useful technique for vaccine delivery by recombinant lactobacilli. In this study, two recombinant Lactobacillus acidophilus derivatives displaying Salmonella flagellin (FliC) were constructed using different anchor motifs. In one instance, the FliC protein was fused to the C-terminal region of a cell envelope proteinase (PrtP) and was bound to the cell wall by electrostatic bonds. In the other case, the same antigen was conjugated to the anchor region of mucus binding protein (Mub) and was covalently associated with the cell wall by an LPXTG motif. These two recombinant L. acidophilus cell surface displays resulted in dissimilar maturation and cytokine production by human myeloid dendritic cells. The surface-associated antigen was highly sensitive to simulated gastric and small intestinal juices. By supplementation with bicarbonate buffer and soybean trypsin inhibitor, the cell surface antigen was protected from proteolytic enzymes during gastric challenge in vitro. The protective reagents also increased the viability of the L. acidophilus cells upon challenge with simulated digestive juices. These results demonstrate the importance of protecting cells and their surface-associated antigens during oral immunization.",,"['Kajikawa, Akinobu', 'Nordone, Shila K.', 'Zhang, Lin', 'Stoeker, Laura L.', 'LaVoy, Alora S.', 'Klaenhammer, Todd R.', 'Dean, Gregg A.']",,,,
,PMC,RIG-I Like Receptors and Their Signaling Crosstalk in the Regulation of Antiviral Immunity,http://dx.doi.org/10.1016/j.coviro.2011.04.004,PMC3177754,,,"During virus infection, multiple immune signaling pathways are triggered, both within the host cell and bystander cells of an infected tissue. These pathways act in concert to mediate innate antiviral immunity and to initiate the inflammatory response against infection. The RIG-I-like receptor (RLR) family of pattern recognition receptors (PRRs) is a group of cytosolic RNA helicase proteins that can identify viral RNA as nonself via binding to pathogen associated molecular patter (PAMP) motifs within RNA ligands that accumulate during virus infection. This interaction then leads to triggering of an innate antiviral response within the infected cells through RLR induction of downstream effector molecules such as type I interferon (IFN) and other pro-inflammatory cytokines that serve to induce antiviral and inflammatory gene expression within the local tissue. Cellular regulation of RLR signaling is a critical process that can direct the outcome of infection and is essential for governance of the overall immune response and avoidance of immune toxicity. Mechanisms of positive and negative regulation of RLR signaling have been identified that include signaling crosstalk between RLR pathways and Nuclear Oligomerization Domain (NOD)-Like Receptor (NLR) pathways and Caspase networks. Furthermore, many viruses have evolved mechanisms to target these pathways to promote enhanced replication and spread within the host. These virus-host interactions therefore carry important consequences for host immunity and viral pathogenesis. Understanding the pivotal role of RLRs in immune regulation and signaling crosstalk in antiviral immunity may provide new insights into therapeutic strategies for the control of virus infection and immunity.",,"['Ramos, Hilario J', 'Gale, Michael']",,,,
,PMC,Clearance of virus infection from the CNS,http://dx.doi.org/10.1016/j.coviro.2011.05.021,PMC3171972,,,"Viruses that cause encephalomyelitis infect neurons and recovery from infection requires noncytolytic clearance of virus from the nervous system to avoid damaging these irreplaceable cells. Several murine model systems of virus infection have been used to identify clearance mechanisms. Quantitative analysis of Sindbis virus clearance over 6 months shows three phases: day 5-7, clearance of infectious virus, but continued presence of viral RNA; day 8-60, decreasing levels of viral RNA; day 60-180, maintenance of viral RNA at low levels. Antiviral antibody and interferon-γ have major roles in clearance with a likely role for IgM as well as IgG antibody. Long-term residence of virus-specific immune cells in the nervous system is necessary to prevent virus reactivation.",,"['Griffin, Diane E.', 'Metcalf, Talibah']",,,,
,PMC,dsRNA sensors and plasmacytoid dendritic cells in host defense and autoimmunity,http://dx.doi.org/10.1111/j.1600-065X.2011.01049.x,PMC3170087,,,"The innate immune system detects viruses through molecular sensors that trigger the production of type I interferons (IFN-I) and inflammatory cytokines. Because viruses vary tremendously in size, structure, genomic composition, and tissue tropism, multiple sensors are required to detect their presence in various cell types and tissues. In this review, we summarize current knowledge of the diversity, specificity, and signaling pathways downstream of viral sensors and ask whether two distinct sensors that recognize the same viral component are complementary, compensatory, or simply redundant. We also discuss why viral sensors are differentially distributed in distinct cell types and whether a particular cell type dominates the IFN-I response during viral infection. Finally, we review evidence suggesting that inappropriate signaling through viral sensors may induce autoimmunity. The picture emerging from these studies is that disparate viral sensors in different cell types form a dynamic and integrated molecular network that can be exploited for improving vaccination and therapeutic strategies for infectious and autoimmune diseases.",,"['Wang, Yaming', 'Swiecki, Melissa', 'McCartney, Stephen A.', 'Colonna, Marco']",,,,
,PMC,Evaluation of the Aesthetics of Physical Methods of Euthanasia of Anesthetized Rats,,PMC3189674,,,"Dissection of living brain tissue for in vitro experiments requires the use of a rapid euthanasia method. However, the method must not subject animals to unnecessary pain and must be aesthetically acceptable to experimenters. The purposes of the current study were to assess the aesthetics of 6 euthanasia methods, measure the procedure duration, and evaluate brain for pathology after each procedure. We digitally recorded euthanasia of isoflurane-anesthetized rats by 6 physical methods: anesthetic overdose, cardiac exsanguination, decapitation, closed intrathoracic transection of the great vessels and heart, thoracic percussion, and thoracotomy with rupture of great vessels. Volunteer researchers and animal caretakers watched the video and completed an associated questionnaire. Anesthetic overdose and cardiac exsanguinations were rated most aesthetically pleasing, although these procedures took the longest to complete. In contrast, decapitation and thoracic percussion were the least aesthetically pleasing, but these methods were the quickest. No demographic factor was identified that could predict whether a given euthanasia procedure would be favored for aesthetic reasons, and participants provided a wide variety of rationales for the aesthetic ratings they assigned. Although all of these euthanasia methods meet the criteria of approved methods of euthanasia of anesthetized rats as defined by the AVMA, aesthetic features and the scientific need for rapid euthanasia are both considerations in selecting a method.",,"['Hickman, Debra L', 'Johnson, Steven W']",,,,
,PMC,Effects of Age of Pups and Removal of Existing Litter on Pup Survival during Cross-Fostering between Multiparous Outbred Mice,,PMC3189666,,,"Periparturient manipulation of mice is a valuable tool for modern research facilities. Although fostering and Caesarian section frequently are used to eradicate pathogens, an often overlooked use is to rescue poorly breeding strains of mice. Here we characterized the weaning success rates after fostering outbred pups of variable ages (younger than 24 h; 5 to 7 d; 10 to 12 d) with full or partial replacement of litters and multiparous dams. There were no significant differences between most groups when analyzed by full or partial replacement or age of donor pups as compared with control groups, in which pups were manipulated but returned to the birth dam or the birth dam was not disturbed. However, significant differences were associated with fostering of 10- to 12-d-old pups in combination with younger pups. Overall, these findings suggest that limiting fostering to pups that are within 48 h of age and age-matching litters when fostering are unnecessary.",,"['Hickman, Debra L', 'Swan, Melissa P']",,,,
,PMC,The Clinical Microbiology Laboratory in the Diagnosis of Lower Respiratory Tract Infections,http://dx.doi.org/10.1128/JCM.00789-11,PMC3185862,,,,,"['Campbell, Sheldon', 'Forbes, Betty A.']",,,,
,PMC,"A 30-Year-Old Male with a 4-Week History of Shortness of Breath, Productive Cough, and Weight Loss",http://dx.doi.org/10.1128/JCM.00875-11,PMC3165590,,,,,"['Munson, Erik', 'Paul, Mary']",,,,
,PMC,Improved Detection of Respiratory Viruses in Pediatric Outpatients with Acute Respiratory Illness by Real-Time PCR Using Nasopharyngeal Flocked Swabs,http://dx.doi.org/10.1128/JCM.02231-10,PMC3165583,,,"Detection of respiratory viruses by real-time multiplexed PCR (M-PCR) and of respiratory syncytial virus (RSV) by M-PCR and immunofluorescence (IF) was evaluated using specimens collected by nasopharyngeal flocked swabbing (NFS) and nasal washes (NW). In children with mild respiratory illness, NFS collection was superior to NW collection for detection of viruses by M-PCR (sensitivity, 89.6% versus 79.2%; P = 0.0043). NFS collection was noninferior to NW collection in the detection of RSV by IF.",,"['Munywoki, Patrick Kiio', 'Hamid, Fauzat', 'Mutunga, Martin', 'Welch, Steve', 'Cane, Patricia', 'Nokes, D. James']",,,,
,PMC,Multiplex Method for Simultaneous Serological Detection of Porcine Reproductive and Respiratory Syndrome Virus and Porcine Circovirus Type 2,http://dx.doi.org/10.1128/JCM.00557-11,PMC3165569,,,"Porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) are major contributors to the porcine respiratory disease complex (PRDC). Routine serological diagnosis and surveillance play an important role in the prevention of PRDC, as it is a leading cause of economic losses to the swine industry. We herein describe an advanced microsphere-based immunoassay that permits the simultaneous detection of antibodies to PCV2 and PRRSV, thereby reducing the time and effort involved in testing. Recombinant PRRSV nucleoprotein antigen and the PCV2 capsid antigen were coupled to fluorophore-dyed beads with distinct spectral addresses. Weekly serum samples from 72 pigs that were experimentally exposed to either PCV2, PRRSV, or both PCV2 and PRRSV were used to validate the microbead assay (MBA) in comparison with the “gold standard” enzyme-linked immunosorbent assays. The kinetics of the PCV2- and PRRSV-specific antibody responses measured by the microbead assay were comparable to those of the standard assays; Spearman's rank correlations were 0.72 (P < 0.001) for PRRSV and 0.80 (P < 0.001) for PCV2. Diagnostic sensitivity and specificity were determined using field sera whose positive or negative status was determined by the standard tests. The diagnostic sensitivity and specificity were both 98% for PCV2 and were 91% and 93%, respectively, for PRRSV (kappa coefficients, 0.85 and 0.67 for PCV2 and PRRSV, respectively). Multiplexing did not interfere with assay performance or diagnostic sensitivity. Therefore, the described study demonstrates proof of concept for the development of more versatile and economical microbead array-based multiplex serological test panels for veterinary use.",,"['Lin, Kathy', 'Wang, Chong', 'Murtaugh, Michael P.', 'Ramamoorthy, Sheela']",,,,
,PMC,Identification of an HLA-DPB1*0501 Restricted Melan-A/MART-1 Epitope Recognized by CD4(+) T Lymphocytes: Prevalence for Immunotherapy in Asian Populations,http://dx.doi.org/10.1097/CJI.0b013e318226bd45,PMC4426979,,,"CD4(+) T lymphocytes play a central role in orchestrating an efficient antitumor immune response. Much effort has been devoted in the identification of major histocompatibility complex class II eptiopes from different tumor-associated antigens. Melan-A/ MART-1 is expressed specifically in normal melanocytes and tumor cells of 75% to 100% of melanoma patients. Melan-A/MART-1 is considered as an attractive target for cancer immunotherapy. In the past, several human leukocyte antigen (HLA) class II restricted epitopes have been identified and characterized, including Melan-A/ MART-1(1-20) (HLA-DR11 restricted),Melan-A/MART-1(25-36) (HLA-DQ6 and HLA-DR3 restricted), Melan-A/MART-1(27-40) (HLA-DR1 restricted), Melan-A/MART-1(51-73) (HLA-DR4 restricted), Melan-A/ MART-1(91-110) (HLA-DR52 restricted), and Melan-A/MART-1(100-111) (HLA-DR1 restricted). Owing to the infrequent expression of the above HLA class II alleles in Asian populations, immunotherapy using these defined Melan-A/MART-1 peptides could potentially only benefit a very small percentage of Asian melanoma patients. In this study, we established several CD4(+) T-cell clones by in vitro stimulation of peripheral blood mononuclear cells from a healthy donor by a peptide pool of 28 to 30 amino acid long peptides spanning the entire Melan-A/MART-1 protein. These CD4(+) T-cell clones recognized a peptide that is embedded within Melan-A/ MART-1(21-50,) in a HLA-DPB1*0501 restricted manner. Finally, we demonstrated that this epitope is naturally processed and presented by dendritic cells. HLA-DPB1*0501 is frequently expressed in Asian population (44.9% to 73.1%). Therefore, this epitope could provide a new tool and could significantly increase the percentage of melanoma patients that can benefit from cancer immunotherapy.",,"['Meng, Zhaoting', 'Wang, Yadong', 'Zhang, Guanzhong', 'Ke, Yuehua', 'Yan, Yanfeng', 'Wu, Liangliang', 'Huang, Qianrong', 'Zeng, Gang', 'Wang, Yu', 'Ying, Han', 'Jiao, Shunchang']",,,,
,PMC,Ebolavirus Δ-Peptide Immunoadhesins Inhibit Marburgvirus and Ebolavirus Cell Entry,http://dx.doi.org/10.1128/JVI.02600-10,PMC3165852,,,"With the exception of Reston and Lloviu viruses, filoviruses (marburgviruses, ebolaviruses, and “cuevaviruses”) cause severe viral hemorrhagic fevers in humans. Filoviruses use a class I fusion protein, GP(1,2), to bind to an unknown, but shared, cell surface receptor to initiate virus-cell fusion. In addition to GP(1,2), ebolaviruses and cuevaviruses, but not marburgviruses, express two secreted glycoproteins, soluble GP (sGP) and small soluble GP (ssGP). All three glycoproteins have identical N termini that include the receptor-binding region (RBR) but differ in their C termini. We evaluated the effect of the secreted ebolavirus glycoproteins on marburgvirus and ebolavirus cell entry, using Fc-tagged recombinant proteins. Neither sGP-Fc nor ssGP-Fc bound to filovirus-permissive cells or inhibited GP(1,2)-mediated cell entry of pseudotyped retroviruses. Surprisingly, several Fc-tagged Δ-peptides, which are small C-terminal cleavage products of sGP secreted by ebolavirus-infected cells, inhibited entry of retroviruses pseudotyped with Marburg virus GP(1,2), as well as Marburg virus and Ebola virus infection in a dose-dependent manner and at low molarity despite absence of sequence similarity to filovirus RBRs. Fc-tagged Δ-peptides from three ebolaviruses (Ebola virus, Sudan virus, and Taï Forest virus) inhibited GP(1,2)-mediated entry and infection of viruses comparably to or better than the Fc-tagged RBRs, whereas the Δ-peptide-Fc of an ebolavirus nonpathogenic for humans (Reston virus) and that of an ebolavirus with lower lethality for humans (Bundibugyo virus) had little effect. These data indicate that Δ-peptides are functional components of ebolavirus proteomes. They join cathepsins and integrins as novel modulators of filovirus cell entry, might play important roles in pathogenesis, and could be exploited for the synthesis of powerful new antivirals.",,"['Radoshitzky, Sheli R.', 'Warfield, Kelly L.', 'Chi, Xiaoli', 'Dong, Lian', 'Kota, Krishna', 'Bradfute, Steven B.', 'Gearhart, Jacqueline D.', 'Retterer, Cary', 'Kranzusch, Philip J.', 'Misasi, John N.', 'Hogenbirk, Marc A.', 'Wahl-Jensen, Victoria', 'Volchkov, Viktor E.', 'Cunningham, James M.', 'Jahrling, Peter B.', 'Aman, M. Javad', 'Bavari, Sina', 'Farzan, Michael', 'Kuhn, Jens H.']",,,,
,PMC,Targeting OX40 Promotes Lung-Resident Memory CD8 T Cell Populations That Protect against Respiratory Poxvirus Infection,http://dx.doi.org/10.1128/JVI.00619-11,PMC3165842,,,"One goal of vaccination is to promote development of mucosal effector cells that can immediately respond to peripheral infection. This is especially important for protection against viruses that enter the host through the respiratory tract. We show that targeting the OX40 costimulatory receptor (CD134) strongly promotes mucosal memory in the CD8 T cell compartment. Systemic injection of an agonist antibody to OX40 strongly enhanced development of polyfunctional effector CD8 T cells that were induced after intraperitoneal infection with a highly virulent strain of vaccinia virus. These cells were located in lymphoid organs and also the lung, and importantly, long-term memory CD8 T cells were maintained in the lung over 1 year. Anti-OX40 also boosted memory development when mice were vaccinated subcutaneously with viral peptide. These CD8 T cells were sufficient to provide protection from lethal respiratory infection with live vaccinia virus independent of CD4 T cells and antibody. Again, the CD8 T cell populations that were induced after secondary infection displayed polyfunctionality and were maintained in the lung for over a year. These data suggest that agonists to the OX40 costimulatory receptor represent potential candidates for incorporation into vaccines for respiratory viruses.",,"['Salek-Ardakani, Shahram', 'Moutaftsi, Magdalini', 'Sette, Alessandro', 'Croft, Michael']",,,,
,PMC,Gene N Proximal and Distal RNA Motifs Regulate Coronavirus Nucleocapsid mRNA Transcription,http://dx.doi.org/10.1128/JVI.00869-11,PMC3165819,,,"Coronavirus subgenomic mRNA (sgmRNA) transcription requires a discontinuous RNA synthesis mechanism driven by the transcription-regulating sequences (TRSs), located at the 3′ end of the genomic leader (TRS-L) and also preceding each gene (TRS-B). In transmissible gastroenteritis virus (TGEV), the free energy of TRS-L and cTRS-B (complement of TRS-B) duplex formation is one of the factors regulating the transcription of sgmRNAs. In addition, N gene sgmRNA transcription is controlled by a transcription-regulating motif, including a long-distance RNA-RNA interaction between complementary proximal and distal elements. The extension of complementarity between these two sequences increased N gene transcription. An active domain, a novel essential component of the transcription-regulating motif, has been identified. The active domain primary sequence was necessary for its activity. Relocation of the active domain upstream of the N gene TRS core sequence in the absence of the proximal and distal elements also enhanced sgmRNA N transcription. According to the proposed working model for N gene transcriptional activation, the long-distance RNA-RNA interaction relocates the distant active domain in close proximity with the N gene TRS, which probably increases the frequency of template switching during the synthesis of negative RNA. The transcription-regulating motif has been optimized to a minimal sequence showing a 4-fold activity increase in relation to the native RNA motif. Full-length TGEV infectious viruses were generated with the optimized transcription-regulating motif, which enhanced by 5-fold the transcription of the 3a gene and can be used in expression vectors based in coronavirus genomes.",,"['Mateos-Gómez, Pedro A.', 'Zuñiga, Sonia', 'Palacio, Lorena', 'Enjuanes, Luis', 'Sola, Isabel']",,,,
,PMC,"Roles of the Fusion and Hemagglutinin-Neuraminidase Proteins in Replication, Tropism, and Pathogenicity of Avian Paramyxoviruses",http://dx.doi.org/10.1128/JVI.00652-11,PMC3165810,,,"Virulent and moderately virulent strains of Newcastle disease virus (NDV), representing avian paramyxovirus serotype 1 (APMV-1), cause respiratory and neurological disease in chickens and other species of birds. In contrast, APMV-2 is avirulent in chickens. We investigated the role of the fusion (F) and hemagglutinin-neuraminidase (HN) envelope glycoproteins in these contrasting phenotypes by designing chimeric viruses in which the F and HN glycoproteins or their ectodomains were exchanged individually or together between the moderately virulent, neurotropic NDV strain Beaudette C (BC) and the avirulent APMV-2 strain Yucaipa. When we attempted to exchange the complete F and HN glycoproteins individually and together between the two viruses, the only construct that could be recovered was recombinant APMV-2 strain Yucaipa (rAPMV-2), containing the NDV F glycoprotein in place of its own. This substitution of NDV F into APMV-2 was sufficient to confer the neurotropic, neuroinvasive, and neurovirulent phenotypes, in spite of all being at reduced levels compared to what was seen for NDV-BC. When the ectodomains of F and HN were exchanged individually and together, two constructs could be recovered: NDV, containing both the F and HN ectodomains of APMV-2; and APMV-2, containing both ectodomains of NDV. This supported the idea that homologous cytoplasmic tails and matched F and HN ectodomains are important for virus replication. Analysis of these viruses for replication in vitro, syncytium formation, mean embryo death time, intracerebral pathogenicity index, and replication and tropism in 1-day-old chicks and 2-week-old chickens showed that the two contrasting phenotypes of NDV and APMV-2 could largely be transferred between the two backbones by transfer of homotypic F and HN ectodomains. Further analysis provided evidence that the homologous stalk domain of NDV HN is essential for virus replication, while the globular head domain of NDV HN could be replaced with that of APMV-2 with only a minimal attenuating effect. These results demonstrate that the F and HN ectodomains together determine the cell fusion, tropism, and virulence phenotypes of NDV and APMV-2 and that the regions of HN that are critical to replication and the species-specific phenotypes include the cytoplasmic tail and stalk domain but not the globular head domain.",,"['Kim, Shin-Hee', 'Subbiah, Madhuri', 'Samuel, Arthur S.', 'Collins, Peter L.', 'Samal, Siba K.']",,,,
,PMC,Binding of Avian Coronavirus Spike Proteins to Host Factors Reflects Virus Tropism and Pathogenicity,http://dx.doi.org/10.1128/JVI.05112-11,PMC3165808,,,"The binding of viruses to host cells is the first step in determining tropism and pathogenicity. While avian infectious bronchitis coronavirus (IBV) infection and avian influenza A virus (IAV) infection both depend on α2,3-linked sialic acids, the host tropism of IBV is restricted compared to that of IAV. Here we investigated whether the interaction between the viral attachment proteins and the host could explain these differences by using recombinant spike domains (S1) of IBV strains with different pathogenicities, as well as the hemagglutinin (HA) protein of IAV H5N1. Protein histochemistry showed that S1 of IBV strain M41 and HA of IAV subtype H5N1 displayed sialic acid-dependent binding to chicken respiratory tract tissue. However, while HA bound with high avidity to a broad range of α2,3-linked sialylated glycans, M41 S1 recognized only one particular α2,3-linked disialoside in a glycan array. When comparing the binding of recombinant IBV S1 proteins derived from IBV strains with known differences in tissue tropism and pathogenicity, we observed that while M41 S1 displayed binding to cilia and goblet cells of the chicken respiratory tract, S1 derived from the vaccine strain H120 or the nonvirulent Beaudette strain had reduced or no binding to chicken tissues, respectively, in agreement with the reduced abilities of these viruses to replicate in vivo. While the S1 protein derived from the nephropathogenic IBV strain B1648 also hardly displayed binding to respiratory tract cells, distinct binding to kidney cells was observed, but only after the removal of sialic acid from S1. In conclusion, our data demonstrate that the attachment patterns of the IBV S proteins correlate with the tropisms and pathogenicities of the corresponding viruses.",,"['Wickramasinghe, I. N. Ambepitiya', 'de Vries, R. P.', 'Gröne, A.', 'de Haan, C. A. M.', 'Verheije, M. H.']",,,,
,PMC,Mouse Hepatitis Virus Stem-Loop 4 Functions as a Spacer Element Required To Drive Subgenomic RNA Synthesis,http://dx.doi.org/10.1128/JVI.05092-11,PMC3165806,,,"The 5′ 140 nucleotides of the mouse hepatitis virus (MHV) 5′ untranslated region (5′UTR) are predicted to contain three secondary structures, stem-loop 1 (SL1), SL2, and SL4. SL1 and SL2 are required for subgenomic RNA synthesis. The current study focuses on SL4, which contains two base-paired regions, SL4a and SL4b. A series of reverse genetic experiments show that SL4a is not required to be base paired. Neither the structure, the sequence, nor the putative 8-amino-acid open reading frame (ORF) in SL4b is required for viral replication. Viruses containing separate deletions of SL4a and SL4b are viable. However, deletion of SL4 is lethal, and genomes carrying this deletion are defective in directing subgenomic RNA synthesis. Deletion of (131)ACA(133) just 3′ to SL4 has a profound impact on viral replication. Viruses carrying the (131)ACA(133) deletion were heterogeneous in plaque size. We isolated three viruses with second-site mutations in the 5′UTR which compensated for decreased plaque sizes, delayed growth kinetics, and lower titers associated with the (131)ACA(133) deletion. The second-site mutations are predicted to change either the spacing between SL1 and SL2 or that between SL2 and SL4 or to destabilize the proximal portion of SL4a in our model. A mutant constructed by replacing SL4 with a shorter sequence-unrelated stem-loop was viable. These results suggest that the proposed SL4 in the MHV 5′UTR functions in part as a spacer element that orients SL1, SL2, and the transcriptional regulatory sequence (TRS), and this spacer function may play an important role in directing subgenomic RNA synthesis.",,"['Yang, Dong', 'Liu, Pinghua', 'Giedroc, David P.', 'Leibowitz, Julian']",,,,
,PMC,"Direct Inhibition of Tombusvirus Plus-Strand RNA Synthesis by a Dominant Negative Mutant of a Host Metabolic Enzyme, Glyceraldehyde-3-Phosphate Dehydrogenase, in Yeast and Plants",http://dx.doi.org/10.1128/JVI.00666-11,PMC3165801,,,"The replication of plus-strand RNA viruses depends on many cellular factors. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an abundant metabolic enzyme that is recruited to the replicase complex of Tomato bushy stunt virus (TBSV) and affects asymmetric viral RNA synthesis. To further our understanding on the role of GAPDH in TBSV replication, we used an in vitro TBSV replication assay based on recombinant p33 and p92(pol) viral replication proteins and cell-free yeast extract. We found that the addition of purified recombinant GAPDH to the cell extract prepared from GAPDH-depleted yeast results in increased plus-strand RNA synthesis and asymmetric production of viral RNAs. Our data also demonstrate that GAPDH interacts with p92(pol) viral replication protein, which may facilitate the recruitment of GAPDH into the viral replicase complex in the yeast model host. In addition, we have identified a dominant negative mutant of GAPDH, which inhibits RNA synthesis and RNA recruitment in vitro. Moreover, this mutant also exhibits strong suppression of tombusvirus accumulation in yeast and in virus-infected Nicotiana benthamiana. Overall, the obtained data support the model that the co-opted GAPDH plays a direct role in TBSV replication by stimulating plus-strand synthesis by the viral replicase.",,"['Huang, Tyng-Shyan', 'Nagy, Peter D.']",,,,
,PMC,Glyceraldehyde 3-Phosphate Dehydrogenase Negatively Regulates the Replication of Bamboo Mosaic Virus and Its Associated Satellite RNA,http://dx.doi.org/10.1128/JVI.00556-11,PMC3165797,,,"The identification of cellular proteins associated with virus replicase complexes is crucial to our understanding of virus-host interactions, influencing the host range, replication, and virulence of viruses. A previous in vitro study has demonstrated that partially purified Bamboo mosaic virus (BaMV) replicase complexes can be employed for the replication of both BaMV genomic and satellite BaMV (satBaMV) RNAs. In this study, we investigated the BaMV and satBaMV 3′ untranslated region (UTR) binding proteins associated with these replicase complexes. Two cellular proteins with molecular masses of ∼35 and ∼55 kDa were specifically cross-linked with RNA elements, whereupon the ∼35-kDa protein was identified as the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Gel mobility shift assays confirmed the direct interaction of GAPDH with the 3′ UTR sequences, and competition gel shift analysis revealed that GAPDH binds preferentially to the positive-strand BaMV and satBaMV RNAs over the negative-strand RNAs. It was observed that the GAPDH protein binds to the pseudoknot poly(A) tail of BaMV and stem-loop-C poly(A) tail of satBaMV 3′ UTR RNAs. It is important to note that knockdown of GAPDH in Nicotiana benthamiana enhances the accumulation of BaMV and satBaMV RNA; conversely, transient overexpression of GAPDH reduces the accumulation of BaMV and satBaMV RNA. The recombinant GAPDH principally inhibits the synthesis of negative-strand RNA in exogenous RdRp assays. These observations support the contention that cytosolic GAPDH participates in the negative regulation of BaMV and satBaMV RNA replication.",,"['Prasanth, K. Reddisiva', 'Huang, Ying-Wen', 'Liou, Ming-Ru', 'Wang, Robert Yung-Liang', 'Hu, Chung-Chi', 'Tsai, Ching-Hsiu', 'Meng, Menghsiao', 'Lin, Na-Sheng', 'Hsu, Yau-Heiu']",,,,
,PMC,Complete Genome Analysis of Three Novel Picornaviruses from Diverse Bat Species,http://dx.doi.org/10.1128/JVI.02364-10,PMC3165794,,,"Although bats are important reservoirs of diverse viruses that can cause human epidemics, little is known about the presence of picornaviruses in these flying mammals. Among 1,108 bats of 18 species studied, three novel picornaviruses (groups 1, 2, and 3) were identified from alimentary specimens of 12 bats from five species and four genera. Two complete genomes, each from the three picornaviruses, were sequenced. Phylogenetic analysis showed that they fell into three distinct clusters in the Picornaviridae family, with low homologies to known picornaviruses, especially in leader and 2A proteins. Moreover, group 1 and 2 viruses are more closely related to each other than to group 3 viruses, which exhibit genome features distinct from those of the former two virus groups. In particular, the group 3 virus genome contains the shortest leader protein within Picornaviridae, a putative type I internal ribosome entry site (IRES) in the 5′-untranslated region instead of the type IV IRES found in group 1 and 2 viruses, one instead of two GXCG motifs in 2A, an L→V substitution in the DDLXQ motif in 2C helicase, and a conserved GXH motif in 3C protease. Group 1 and 2 viruses are unique among picornaviruses in having AMH instead of the GXH motif in 3C(pro). These findings suggest that the three picornaviruses belong to two novel genera in the Picornaviridae family. This report describes the discovery and complete genome analysis of three picornaviruses in bats, and their presence in diverse bat genera/species suggests the ability to cross the species barrier.",,"['Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Lai, Kenneth K. Y.', 'Huang, Yi', 'Yip, Cyril C. Y.', 'Shek, Chung-Tong', 'Lee, Paul', 'Lam, Carol S. F.', 'Chan, Kwok-Hung', 'Yuen, Kwok-Yung']",,,,
,PMC,Green Fluorescent Protein Reporter System with Transcriptional Sequence Heterogeneity for Monitoring the Interferon Response,http://dx.doi.org/10.1128/JVI.00772-11,PMC3165742,,,"The interferon (IFN) response is initiated by a variety of triggers, including viruses and foreign RNA, and involves several receptors and intracellular mediators. Although there are common cis-acting consensus sequences in the promoters of many genes stimulated during the IFN response, they exhibit core and context heterogeneity that may lead to differential transcriptional activity. We have developed and validated a live cell-based enhanced green fluorescent protein (EGFP) reporter system employing more than a hundred constructs containing multiple viruses and IFN response elements derived from a variety of promoters involved in immunity to viruses. Common and distinct response patterns were observed due to promoter heterogeneity in response to different stimuli, including IFN-α, TLR3-agonist double-stranded RNA, and several viruses. This information should serve as a resource in selecting specific reporters for sensing nonself ligands.",,"['Mahmoud, Linah', 'Al-Saif, Maher', 'Amer, Haitham M.', 'Sheikh, Mustafa', 'Almajhdi, Fahad N.', 'Khabar, Khalid S. A.']",,,,
,PMC,Interplay between Innate Immunity and Negative-Strand RNA Viruses: towards a Rational Model,http://dx.doi.org/10.1128/MMBR.00007-11,PMC3165544,,,"Summary: The discovery of a new class of cytosolic receptors recognizing viral RNA, called the RIG-like receptors (RLRs), has revolutionized our understanding of the interplay between viruses and host cells. A tremendous amount of work has been accumulating to decipher the RNA moieties required for an RLR agonist, the signal transduction pathway leading to activation of the innate immunity orchestrated by type I interferon (IFN), the cellular and viral regulators of this pathway, and the viral inhibitors of the innate immune response. Previous reviews have focused on the RLR signaling pathway and on the negative regulation of the interferon response by viral proteins. The focus of this review is to put this knowledge in the context of the virus replication cycle within a cell. Likewise, there has been an expansion of knowledge about the role of innate immunity in the pathophysiology of viral infection. As a consequence, some discrepancies have arisen between the current models of cell-intrinsic innate immunity and current knowledge of virus biology. This holds particularly true for the nonsegmented negative-strand viruses (Mononegavirales), which paradoxically have been largely used to build presently available models. The aim of this review is to bridge the gap between the virology and innate immunity to favor the rational building of a relevant model(s) describing the interplay between Mononegavirales and the innate immune system.",,"['Gerlier, Denis', 'Lyles, Douglas S.']",,,,
,PMC,The Universally Conserved Prokaryotic GTPases,http://dx.doi.org/10.1128/MMBR.00009-11,PMC3165542,,,"Summary: Members of the large superclass of P-loop GTPases share a core domain with a conserved three-dimensional structure. In eukaryotes, these proteins are implicated in various crucial cellular processes, including translation, membrane trafficking, cell cycle progression, and membrane signaling. As targets of mutation and toxins, GTPases are involved in the pathogenesis of cancer and infectious diseases. In prokaryotes also, it is hard to overestimate the importance of GTPases in cell physiology. Numerous papers have shed new light on the role of bacterial GTPases in cell cycle regulation, ribosome assembly, the stress response, and other cellular processes. Moreover, bacterial GTPases have been identified as high-potential drug targets. A key paper published over 2 decades ago stated that, “It may never again be possible to capture [GTPases] in a family portrait” (H. R. Bourne, D. A. Sanders, and F. McCormick, Nature 348:125-132, 1990) and indeed, the last 20 years have seen a tremendous increase in publications on the subject. Sequence analysis identified 13 bacterial GTPases that are conserved in at least 75% of all bacterial species. We here provide an overview of these 13 protein subfamilies, covering their cellular functions as well as cellular localization and expression levels, three-dimensional structures, biochemical properties, and gene organization. Conserved roles in eukaryotic homologs will be discussed as well. A comprehensive overview summarizing current knowledge on prokaryotic GTPases will aid in further elucidating the function of these important proteins.",,"['Verstraeten, Natalie', 'Fauvart, Maarten', 'Versées, Wim', 'Michiels, Jan']",,,,
,PMC,A conserved RNA pseudoknot in a putative molecular switch domain of the 3′-untranslated region of coronaviruses is only marginally stable,http://dx.doi.org/10.1261/rna.2816711,PMC3162339,,,"The 3′-untranslated region (UTR) of the group 2 coronavirus mouse hepatitis virus (MHV) genome contains a predicted bulged stem–loop (designated P0ab), a conserved cis-acting pseudoknot (PK), and a more distal stem–loop (designated P2). Base-pairing to create the pseudoknot-forming stem (P1(pk)) is mutually exclusive with formation of stem P0a at the base of the bulged stem–loop; as a result, the two structures cannot be present simultaneously. Herein, we use thermodynamic methods to evaluate the ability of individual subdomains of the 3′ UTR to adopt a pseudoknotted conformation. We find that an RNA capable of forming only the predicted PK (58 nt; 3′ nucleotides 241–185) adopts the P2 stem–loop with little evidence for P1(pk) pairing in 0.1 M KCl and the absence of Mg(2+); as Mg(2+) or 1 M KCl is added, a new thermal unfolding transition is induced and assignable to P1(pk) pairing. The P1(pk) helix is only marginally stable, ΔG(25) ≈ 1.2 ± 0.3 kcal/mol (5.0 mM Mg(2+), 100 mM K(+)), and unfolded at 37°C. Similar findings characterize an RNA 5′ extended through the P0b helix only (89 nt; 294–185). In contrast, an RNA capable of forming either the P0a helix or the pseudoknot (97 nt; 301–185) forms no P1(pk) helix. Thermal unfolding simulations are fully consistent with these experimental findings. These data reveal that the PK forms weakly and only when the competing double-hairpin structure cannot form; in the UTR RNA, the double hairpin is the predominant conformer under all solution conditions.",,"['Stammler, Suzanne N.', 'Cao, Song', 'Chen, Shi-Jie', 'Giedroc, David P.']",,,,
,PMC,Exosomes and the kidney: prospects for diagnosis and therapy of renal diseases,http://dx.doi.org/10.1038/ki.2011.292,PMC3412193,,,"Exosomes are 40–100 nm membrane vesicles secreted into the extracellular space by numerous cell types. These structures can be isolated from body fluids including urine and plasma. Exosomes contain proteins, mRNAs, miRNAs, and signaling molecules that reflect the physiological state of their cells of origin and consequently provide a rich source of potential biomarker molecules. Aside from diagnostic uses, exosome-mediated transfer of proteins, mRNAs, miRNAs, and signaling molecules offer the promise that they may be used for therapeutic purposes. In this review, we integrate new knowledge about exosomes from outside the field of nephrology with recent progress by renal researchers in order to provide a basis for speculation about how the study of exosomes may impact the fields of nephrology and renal physiology in the next few years.",,"['van Balkom, Bas W.M.', 'Pisitkun, Trairak', 'Verhaar, Marianne C.', 'Knepper, Mark A.']",,,,
,PMC,Role of the Endoplasmic Reticulum-associated Degradation (ERAD) Pathway in Degradation of Hepatitis C Virus Envelope Proteins and Production of Virus Particles,http://dx.doi.org/10.1074/jbc.M111.259085,PMC3199473,,,"Viral infections frequently cause endoplasmic reticulum (ER) stress in host cells leading to stimulation of the ER-associated degradation (ERAD) pathway, which subsequently targets unassembled glycoproteins for ubiquitylation and proteasomal degradation. However, the role of the ERAD pathway in the viral life cycle is poorly defined. In this paper, we demonstrate that hepatitis C virus (HCV) infection activates the ERAD pathway, which in turn controls the fate of viral glycoproteins and modulates virus production. ERAD proteins, such as EDEM1 and EDEM3, were found to increase ubiquitylation of HCV envelope proteins via direct physical interaction. Knocking down of EDEM1 and EDEM3 increased the half-life of HCV E2, as well as virus production, whereas exogenous expression of these proteins reduced the production of infectious virus particles. Further investigation revealed that only EDEM1 and EDEM3 bind with SEL1L, an ER membrane adaptor protein involved in translocation of ERAD substrates from the ER to the cytoplasm. When HCV-infected cells were treated with kifunensine, a potent inhibitor of the ERAD pathway, the half-life of HCV E2 increased and so did virus production. Kifunensine inhibited the binding of EDEM1 and EDEM3 with SEL1L, thus blocking the ubiquitylation of HCV E2 protein. Chemical inhibition of the ERAD pathway neither affected production of the Japanese encephalitis virus (JEV) nor stability of the JEV envelope protein. A co-immunoprecipitation assay showed that EDEM orthologs do not bind with JEV envelope protein. These findings highlight the crucial role of the ERAD pathway in the life cycle of specific viruses.",,"['Saeed, Mohsan', 'Suzuki, Ryosuke', 'Watanabe, Noriyuki', 'Masaki, Takahiro', 'Tomonaga, Mitsunori', 'Muhammad, Amir', 'Kato, Takanobu', 'Matsuura, Yoshiharu', 'Watanabe, Haruo', 'Wakita, Takaji', 'Suzuki, Tetsuro']",,,,
,PMC,Complementary roles of Fas-associated death domain (FADD) and receptor interacting protein kinase-3 (RIPK3) in T-cell homeostasis and antiviral immunity,http://dx.doi.org/10.1073/pnas.1102779108,PMC3174674,,,"Caspase-8 (casp8) is required for extrinsic apoptosis, and mice deficient in casp8 fail to develop and die in utero while ultimately failing to maintain the proliferation of T cells, B cells, and a host of other cell types. Paradoxically, these failures are not caused by a defect in apoptosis, but by a presumed proliferative function of this protease. Indeed, following mitogenic stimulation, T cells lacking casp8 or its adaptor protein FADD (Fas-associated death domain protein) develop a hyperautophagic morphology, and die a programmed necrosis-like death process termed necroptosis. Recent studies have demonstrated that receptor-interacting protein kinases (RIPKs) RIPK1 and RIPK3 together facilitate TNF-induced necroptosis, but the precise role of RIPKs in the demise of T cells lacking FADD or casp8 activity is unknown. Here we demonstrate that RIPK3 and FADD have opposing and complementary roles in promoting T-cell clonal expansion and homeostasis. We show that the defective proliferation of T cells bearing an interfering form of FADD (FADDdd) is rescued by crossing with RIPK3(−/−) mice, although such rescue ultimately leads to lymphadenopathy. Enhanced recovery of these double-mutant T cells following stimulation demonstrates that FADD, casp8, and RIPK3 are all essential for clonal expansion, contraction, and antiviral responses. Finally, we demonstrate that caspase-mediated cleavage of RIPK1-containing necrosis inducing complexes (necrosomes) is sufficient to prevent necroptosis in the face of death receptor signaling. These studies highlight the “two-faced” nature of casp8 activity, promoting clonal expansion in some situations and apoptotic demise in others.",,"['Lu, Jennifer V.', 'Weist, Brian M.', 'van Raam, Bram J.', 'Marro, Brett S.', 'Nguyen, Long V.', 'Srinivas, Prathna', 'Bell, Bryan D.', 'Luhrs, Keith A.', 'Lane, Thomas E.', 'Salvesen, Guy S.', 'Walsh, Craig M.']",,,,
,PMC,In vitro transcriptomic prediction of hepatotoxicity for early drug discovery,http://dx.doi.org/10.1016/j.jtbi.2011.08.009,PMC3386613,,,"Liver toxicity (hepatotoxicity) is a critical issue in drug discovery and development. Standard preclinical evaluation of drug hepatotoxicity is generally performed using in vivo animal systems. However, only a small number of preselected compounds can be examined in vivo due to high experimental costs. A more efficient yet accurate screening technique which can identify potentially hepatotoxic compounds in the early stages of drug development would thus be valuable. Here, we develop and apply a novel genomic prediction technique for screening hepatotoxic compounds based on in vitro human liver cell tests. Using a training set of in vivo rodent experiments for drug hepatotoxicity evaluation, we discovered common biomarkers of drug-induced liver toxicity among six heterogeneous compounds. This gene set was further triaged to a subset of 32 genes that can be used as a multi-gene expression signature to predict hepatotoxicity. This multi-gene predictor was independently validated and showed consistently high prediction performance on five test sets of in vitro human liver cell and in vivo animal toxicity experiments. The predictor also demonstrated utility in evaluating different degrees of toxicity in response to drug concentrations which may be useful not only for discerning a compound’s general hepatotoxicity but also for determining its toxic concentration.",,"['Cheng, Feng', 'Theodorescu, Dan', 'Schulman, Ira G.', 'Lee, Jae K.']",,,,
,PMC,CD8(+) T Cells: Foot Soldiers of the Immune System,http://dx.doi.org/10.1016/j.immuni.2011.07.010,PMC3303224,,,"Resting naive CD8(+) T cells have an astounding capacity to react to pathogens by massive expansion and differentiation into cytotoxic effector cells that migrate to all corners of the body to clear the infection. The initial interaction with antigen-presenting cells in the central lymphoid organs drives an orchestrated program of differentiation aimed at producing sufficient numbers of effectors to get the job done without resulting in clonal exhaustion. Interactions with antigen-presenting cells and other immune cells continue at the site of infection to regulate further on-site expansion and differentiation, all with the goal of protecting the host with minimal bystander tissue damage. Here we review recent advances in CD8(+) T cell recognition of antigen in lymphoid as well as in nonlymphoid tissues in the periphery, and how CD8(+) T cell expansion and differentiation are controlled in these contexts.",,"['Zhang, Nu', 'Bevan, Michael J.']",,,,
,PMC,EFFECT OF SIALODACRYOADENITIS VIRUS INFECTION ON AXONAL REGENERATION,http://dx.doi.org/10.1002/micr.20914,PMC4088328,,,"The effect of sialodacryoadenitis virus (SDAV) infection on axonal regeneration and functional recovery was investigated in male Lewis rats. Animals underwent unilateral tibial nerve transection, immediate repair, and treatment with either FK506 (treated) or control vehicle (untreated). Serial walking track analyses were performed to assess functional recovery. Nerves were harvested for morphometric analysis on postoperative day 18 after an SDAV outbreak occurred that affected the 12 experimental animals. Histomorphometry and walking track data were compared against 36 historical controls. Rats infected with SDAV demonstrated severely impaired axonal regeneration and diminished functional recovery. Total fiber counts, nerve density, and percent neural tissue were all significantly reduced in infected animals (P < 0.05). Active SDAV infection severely impaired nerve regeneration and negated the positive effect of FK506 on nerve regeneration in rats. Immunosuppressive risks must be weighed carefully against the potential neuroregenerative benefits in the treatment of peripheral nerve injuries.",,"['YU, VIVIAN M.', 'MACKINNON, SUSAN E.', 'HUNTER, DANIEL A.', 'BRENNER, MICHAEL J.']",,,,
,PMC,Non-Invasive Sample Collection for Respiratory Virus Testing by Multiplex PCR,http://dx.doi.org/10.1016/j.jcv.2011.07.015,PMC3196801,,,"BACKGROUND: Identifying respiratory pathogens within populations is difficult because invasive sample collection, such as with nasopharyngeal aspirate (NPA), is generally required. PCR technology could allow for non-invasive sampling methods. OBJECTIVES: Evaluate the utility of non-invasive sample collection using anterior nare swabs and facial tissues for respiratory virus detection by multiplex PCR. STUDY DESIGN: Children aged 1 month – 17 years evaluated in a pediatric emergency department for respiratory symptoms had a swab, facial tissue, and NPA sample collected. All samples were tested for respiratory viruses by multiplex PCR. Viral detection rates were calculated for each collection method. Sensitivity and specificity of swabs and facial tissues were calculated using NPA as the gold standard. RESULTS: 285 samples from 95 children were evaluated (92 swab-NPA pairs, 91 facial tissue-NPA pairs). 91% of NPA, 82% of swab, and 77% of tissue samples were positive for ≥ 1 virus. Respiratory syncytial virus (RSV) and human rhinovirus (HRV) were most common. Overall, swabs were positive for 74% of virus infections, and facial tissues were positive for 58%. Sensitivity ranged from 17–94% for swabs and 33–84% for tissues. Sensitivity was highest for RSV (94% swabs and 84% tissues). Specificity was ≥ 95% for all viruses except HRV for both collection methods. CONCLUSIONS: Sensitivity of anterior nare swabs and facial tissues in the detection of respiratory viruses by multiplex PCR varied by virus type. Given its simplicity and specificity, non-invasive sampling for PCR testing may be useful for conducting epidemiologic or surveillance studies in settings where invasive testing is impractical or not feasible.",,"['Blaschke, Anne J.', 'Allison, Mandy A.', 'Meyers, Lindsay', 'Rogatcheva, Margarita', 'Heyrend, Caroline', 'Mallin, Brittany', 'Carter, Marjorie', 'LaFleur, Bonnie', 'Barney, Trenda', 'Poritz, Mark A.', 'Daly, Judy A.', 'Byington, Carrie L.']",,,,
,PMC,An Overview of Enzymatic Reagents for the Removal of Affinity Tags,http://dx.doi.org/10.1016/j.pep.2011.08.005,PMC3195948,,,"Although they are often exploited to facilitate the expression and purification of recombinant proteins, every affinity tag, whether large or small, has the potential to interfere with the structure and function of its fusion partner. For this reason, reliable methods for removing affinity tags are needed. Only enzymes have the requisite specificity to be generally useful reagents for this purpose. In this review, the advantages and disadvantages of some commonly used endo- and exoproteases are discussed in light of the latest information.",,"Waugh, David S.",,,,
,PMC,Progress in Respiratory Virus Vaccine Development,http://dx.doi.org/10.1055/s-0031-1283289,PMC4547785,,,"Viral respiratory infections cause significant morbidity and mortality in infants and young children as well as in at-risk adults and the elderly. Although many viral pathogens are capable of causing respiratory disease, vaccine development has to focus on a limited number of pathogens, such as those that commonly cause serious lower respiratory illness (LRI). Whereas influenza virus vaccines have been available for some time (see the review by Clark and Lynch in this issue), vaccines against other medically important viruses such as respiratory syncytial virus (RSV), the parainfluenza viruses (PIVs), and metapneumovirus (MPVs) are not available. This review aims to provide a brief update on investigational vaccines against RSV, the PIVs, and MPV that have been evaluated in clinical trials or are currently in clinical development.",,"Schmidt, Alexander C.",,,,
,PMC,Respiratory Viral Infections in Hematopoietic Stem Cell and Solid Organ Transplant Recipients,http://dx.doi.org/10.1055/s-0031-1283286,PMC4209842,,,"Respiratory viral infections (RVIs) are common causes of mild illness in immunocompetent children and adults with rare occurrences of significant morbidity or mortality. Complications are more common in the very young, very old, and those with underlying lung diseases. However, RVIs are increasingly recognized as a cause of morbidity and mortality in recipients of hematopoietic stem cell transplants (HSCT) and solid organ transplants (SOTs). Diagnostic techniques for respiratory syncytial virus (RSV), parainfluenza, influenza, and adenovirus have been clinically available for decades, and these infections are known to cause serious disease in transplant recipients. Modern molecular technology has now made it possible to detect other RVIs including human metapneumovirus, coronavirus, and bocavirus, and the role of these viruses in causing serious disease in transplant recipients is still being worked out. This article reviews the current information regarding epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment of these infections, as well as the aspects of clinical significance of RVIs unique to HSCT or SOT.",,"['Weigt, S. Samuel', 'Gregson, Aric L.', 'Deng, Jane C.', 'Lynch, Joseph P.', 'Belperio, John A.']",,,,
,PMC,HTLV-1 bZIP factor enhances TGF-β signaling through p300 coactivator,http://dx.doi.org/10.1182/blood-2010-12-326199,PMC3158717,,,"Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that is etiologically associated with adult T-cell leukemia. The HTLV-1 bZIP factor (HBZ), which is encoded by the minus strand of the provirus, is involved in both regulation of viral gene transcription and T-cell proliferation. We showed in this report that HBZ interacted with Smad2/3, and enhanced transforming growth factor-β (TGF-β)/Smad transcriptional responses in a p300-dependent manner. The N-terminal LXXLL motif of HBZ was responsible for HBZ-mediated TGF-β signaling activation. In a serial immunoprecipitation assay, HBZ, Smad3, and p300 formed a ternary complex, and the association between Smad3 and p300 was markedly enhanced in the presence of HBZ. In addition, HBZ could overcome the repression of the TGF-β response by Tax. Finally, HBZ expression resulted in enhanced transcription of Pdgfb, Sox4, Ctgf, Foxp3, Runx1, and Tsc22d1 genes and suppression of the Id2 gene; such effects were similar to those by TGF-β. In particular, HBZ induced Foxp3 expression in naive T cells through Smad3-dependent TGF-β signaling. Our results suggest that HBZ, by enhancing TGF-β signaling and Foxp3 expression, enables HTLV-1 to convert infected T cells into regulatory T cells, which is thought to be a critical strategy for virus persistence.",,"['Zhao, Tiejun', 'Satou, Yorifumi', 'Sugata, Kenji', 'Miyazato, Paola', 'Green, Patrick L.', 'Imamura, Takeshi', 'Matsuoka, Masao']",,,,
,PMC,Limiting the Spread of Highly Resistant Hospital Acquired Microorganisms Via Critical Care Transfers: A Simulation Study,http://dx.doi.org/10.1007/s00134-011-2341-y,PMC3362134,,,"PURPOSE: Hospital-acquired infections with highly resistant organisms are an important problem among critically ill patients. Control of these organisms has largely focused within individual hospitals. We examine the extent to which transfers of critically ill patients could be a vector for wide spread of highly resistant organisms, and compare the efficiency of different approaches to targeting infection control resources. METHODS: We analyzed the network of interhospital transfers of intensive care unit patients in 2005 U.S. Medicare data and 2004–2006 Pennsylvania all-payer data. We simulated spread of highly resistant hospital-acquired infections by randomly choosing a single hospital to develop a highly resistant organism and following spread of infection or colonization throughout the network under varying strategies of infection control and varying levels of infectivity. RESULTS: Critical care transfers could spread a highly resistant organism between any two U.S. hospitals in a median of three years. Hospitals varied substantially in their importance to limiting potential spread. Targeting resources to a small subset of hospitals based on their position in the transfer network was 16 times more efficient than distributing infection control resources uniformly. Within any set of targeted hospitals, the best strategy for infection control heavily concentrated resources at a few particularly important hospitals, regardless of level of infectivity. CONCLUSIONS: Critical care transfers provide a plausible vector for wide-spread dissemination of highly resistant hospital-acquired microorganisms. Infection control efforts can be made more efficient by selectively targeting hospitals most important for transmission.",,"['Karkada, Umanka H.', 'Adamic, Lada A.', 'Kahn, Jeremy M.', 'Iwashyna, Theodore J.']",,,,
,PMC,IFN-λs,http://dx.doi.org/10.1016/j.coi.2011.07.007,PMC3196341,,,"For decades, type I IFNs have been considered indispensable and unique antiviral mediators for the activation of rapid innate antiviral protection. However, the recent discovery of type III IFNs is challenging this paradigm. Since their identification in 2002/2003 by two independent groups, type III IFNs or IFN-λs, also known as IL-28/29, have been the subject of increased study with consequent recognition of their importance in virology and immunology. Initial reports suggested that IFN-λs functionally resemble type I IFNs. Although IFN-λs and classical type I IFNs (IFN-α/β) utilize distinct receptor complexes for signaling, both types of IFNs activate similar intracellular signaling pathways and biological activities, including the ability to induce antiviral state in cells, and both type I and type III IFNs are induced by viral infection. However, different antiviral potency, pattern of their induction and differential tissue expression of their corresponding receptor subunits suggest that the type I and type III IFN antiviral systems do not merely duplicate each other. Recent studies have started to reveal unique biological activities of IFN-λs in and beyond innate antiviral immunity.",,"Kotenko, Sergei V.",,,,
,PMC,Multiple CD4(+) T cell subsets produce immunomodulatory interleukin-10 during respiratory syncytial virus infection,http://dx.doi.org/10.4049/jimmunol.1100764,PMC3304096,,,"The host immune response is believed to contribute to the severity of pulmonary disease induced by acute respiratory syncytial virus (RSV) infection. Because RSV-induced pulmonary disease is associated with immunopathology, we evaluated the role of IL-10 in modulating the RSV-specific immune response. We found that IL-10 protein levels in the lung were increased following acute RSV infection with maximum production corresponding to the peak of the virus-specific T cell response. The majority of IL-10 producing cells in the lung during acute RSV infection were CD4(+) T cells. The IL-10-producing CD4(+) T cells included Foxp3(+)T(regs), Foxp3(−) CD4(+) T cells that co-produce IFN-γ, and Foxp3(−) CD4(+) T cells that do not co-produce IFN-γ. RSV infection of IL-10-deficient mice resulted in more severe disease, as measured by increased weight loss and airway resistance, as compared to control mice. We also observed an increase in the magnitude of the RSV-induced CD8(+) and CD4(+) T cell response that correlated with increased disease severity in the absence of IL-10 or following IL-10R blockade. Interestingly, IL-10R blockade during acute RSV infection altered CD4(+) T cell subset distribution, resulting in a significant increase in IL-17A-producing CD4(+) T cells and a concomitant decrease in Foxp3(+) regulatory T cells. These results demonstrate that IL-10 plays a critical role in modulating the adaptive immune response to RSV by limiting T-cell-mediated pulmonary inflammation and injury.",,"['Weiss, Kayla A.', 'Christiaansen, Allison F.', 'Fulton, Ross B.', 'Meyerholz, David K.', 'Varga, Steven M.']",,,,
,PMC,Global Rinderpest Eradication: Lessons Learned and Why Humans Should Celebrate Too,http://dx.doi.org/10.1093/infdis/jir327,PMC3144172,,,,,"['Morens, David M.', 'Holmes, Edward C.', 'Davis, A. Sally', 'Taubenberger, Jeffery K.']",,,,
,PMC,Inference for discretely observed stochastic kinetic networks with applications to epidemic modeling,http://dx.doi.org/10.1093/biostatistics/kxr019,PMC3276272,,,"We present a new method for Bayesian Markov Chain Monte Carlo–based inference in certain types of stochastic models, suitable for modeling noisy epidemic data. We apply the so-called uniformization representation of a Markov process, in order to efficiently generate appropriate conditional distributions in the Gibbs sampler algorithm. The approach is shown to work well in various data-poor settings, that is, when only partial information about the epidemic process is available, as illustrated on the synthetic data from SIR-type epidemics and the Center for Disease Control and Prevention data from the onset of the H1N1 pandemic in the United States.",,"['Choi, Boseung', 'Rempala, Grzegorz A.']",,,,
,PMC,Development of autoimmune diabetes in the absence of detectable interleukin-17A in a CD8-driven virally-induced model,http://dx.doi.org/10.4049/jimmunol.1000180,PMC3169711,,,"Recent studies have shown that IL-17 can contribute beneficially to pathogen defense, but also that excessive IL-17 levels are associated with chronic inflammation and autoimmune disorders. So far, the role of IL-17 in viral infections and type 1 diabetes is ambiguous. In this study, we used IL-17A eGFP bicistronic reporter mouse strains to analyze in situ production of IL-17A. Upon Klebsiella pneumonia bacterial infection, CD4(+) and γδ T cells produce IL-17A. In contrast, CD4(+) or CD8(+) T cells do not produce IL-17A in response to acute or protracted viral infection with lymphocytic choriomeningitis virus (LCMV), or during autoimmune diabetes development in the CD8-driven LCMV-induced model of type 1 diabetes. We conclude that viral elimination and type 1 diabetes can occur in the absence of detectable IL-17A production, suggesting IL-17A is not essential in these settings.",,"['Van Belle, Tom L.', 'Esplugues, Enric', 'Liao, Jeanette', 'Juntti, Therese', 'Flavell, Richard A.', 'von Herrath, Matthias G.']",,,,
,PMC,Comparative study of codon substitution patterns in foot-and-mouth disease virus (serotype O),http://dx.doi.org/10.3858/emm.2011.43.10.066,PMC3222820,,,"We compared genetic variations in the VP1 gene of foot-and-mouth disease viruses (FMDVs) isolated since 2000 from various region of the world. We analyzed relative synonymous codon usage (RSCU) and phylogenetic relationship between geographical regions, and calculated the genetic substitution patterns between Korean isolate and those from other countries. We calculated the ratios of synonymously substituted codons (SSC) to all observed substitutions and developed a new analytical parameter, EMC (the ratio of exact matching codons within each synonymous substitution group) to investigate more detailed substitution patterns within each synonymous codon group. We observed that FMDVs showed distinct RSCU patterns according to phylogenetic relationships in the same serotype (serotype O). Moreover, while the SSC and EMC values of FMDVs decreased according to phylogenetic distance, G + C composition at the third codon position was strictly conserved. Although there was little variation among the SSC values of 18 amino acids, more dynamic differences were observed in EMC values. The EMC values of 4- and 6-fold degenerate amino acids showed significantly lower values while most 2-fold degenerate amino acids showed no significant difference. Our findings suggest that different EMC patterns among the 18 amino acids might be an important factor in determining the direction of evolution in FMDV.",,"['Ahn, Insung', 'Bae, Se-Eun', 'Son, Hyeon Seok']",,,,
,PMC,CXCR4 Signaling Regulates Remyelination by Endogenous Oligodendrocyte Progenitor Cells in a Viral Model of Demyelination,http://dx.doi.org/10.1002/glia.21225,PMC5025299,,,"Following intracranial infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV), susceptible mice will develop widespread myelin destruction that results in pathological and clinical outcomes similar to those seen in humans with the demyelinating disease Multiple Sclerosis (MS). Partial remyelination and clinical recovery occurs during the chronic phase following control of viral replication yet the signaling mechanisms regulating these events remain enigmatic. Here we report the kinetics of proliferation and maturation of oligodendrocyte progenitor cells (OPCs) within the spinal cord following JHMV-induced demyelination and that CXCR4 signaling contributes to the maturation state of OPCs. Following treatment with AMD3100, a specific inhibitor of CXCR4, mice recovering from widespread demyelination exhibit a significant (P < 0.01) increase in the number of OPCs and fewer (P < 0.05) mature oligodendrocytes compared with HBSS-treated animals. These results suggest that CXCR4 signaling is required for OPCs to mature and contribute to remyelination in response to JHMV-induced demyelination. To assess if this effect is reversible and has potential therapeutic benefit, we pulsed mice with AMD3100 and then allowed them to recover. This treatment strategy resulted in increased numbers of mature oligodendrocytes, enhanced remyelination, and improved clinical outcome. These findings highlight the possibility to manipulate OPCs in order to increase the pool of remyelination-competent cells that can participate in recovery.",,"['CARBAJAL, KEVIN S.', 'MIRANDA, JUAN L.', 'TSUKAMOTO, MICHELLE R.', 'LANE, THOMAS E.']",,,,
,PMC,Antiviral RNAi: Translating Science Toward Therapeutic Success,http://dx.doi.org/10.1007/s11095-011-0549-8,PMC5012899,,,"Viruses continuously evolve to contend with an ever-changing environment that involves transmission between hosts and sometimes species, immune responses, and in some cases therapeutic interventions. Given the high mutation rate of viruses relative to the timescales of host evolution and drug development, novel drug classes that are readily screened and translated to the clinic are needed. RNA interference (RNAi) – a natural mechanism for specific degradation of target RNAs that is conserved from plants to invertebrates and vertebrates – can potentially be harnessed to yield therapies with extensive specificity, ease of design, and broad application. In this review, we discuss basic mechanisms of action and therapeutic applications of RNAi, including design considerations and areas for future development in the field.",,,,,,
,PMC,The Host Interactome of Influenza Virus Presents New Potential Targets for Antiviral Drugs,http://dx.doi.org/10.1002/rmv.703,PMC3207218,,,"Increasing antiviral drug resistance is a major concern for treating influenza, especially in a pandemic setting when the availability of a protective vaccine is uncertain. Resistance is often an issue with drugs directed at viral proteins and for small RNA viruses there are also a limited number of viral proteins that are amenable to inhibition by a small molecule. A new approach that is gaining support is that cellular proteins, which facilitate virus replication, may be used as alternative targets. Whereas drugs directed at viral proteins tend to be virus-specific, drugs directed at host targets have the potential to have broad-spectrum antiviral activity as many viruses may share a dependency on that host function. For influenza virus, we have very limited knowledge of which cellular factors are involved in virus replication, let alone which of these have suitable properties to serve as drug targets. Through the use of high-throughput RNA interference screens, several studies have addressed this gap in our knowledge. The resulting datasets provide new insight into host pathways that are involved in the influenza virus replication cycle and identify specific host factors in these pathways that may serve as potential targets for future antiviral drug development.",,"Shaw, Megan L.",,,,
,PMC,Function of nonstructural 5A protein of genotype 2a in replication and infection of HCV with gene substitution,http://dx.doi.org/10.3748/wjg.v17.i29.3398,PMC3160566,,,"AIM: To explore the function of Nonstructural 5A (NS5A) protein of genotype 2a (JFH1) in the replication and infection of hepatitis C virus (HCV). METHODS: Intergenotypic chimera FL-J6JFH/J4NS5A was constructed by inserting NS5A gene from 1b stain HC-J4 by the overlapping polymerase chain reaction (PCR) method and the restriction enzyme reaction. In vitro RNA transcripts of chimera, prototype J6JFH and negative control J6JFH1 (GND) were prepared and transfected into Huh-7.5 cells with liposomes. Immunofluorescence assay (IFA), fluorescence quantitative PCR and infection assay were performed to determine the protein expression and gene replication in Huh-7.5 cells. RESULTS: The HCV RNA levels in FL-J6JFH/J4NS5A chimera RNA transfected cells were significantly lower than the wild type at any indicated time point (2.58 ± 5.97 × 10(6) vs 4.27 ± 1.72 × 10(4), P = 0.032). The maximal level of HCV RNA in chimera was 5.6 ± 1.8 × 10(4) GE/μg RNA at day 34 after transfection, while the wild type reached a peak level at day 13 which was 126 folds higher (70.65 ± 14.11 × 10(5) vs 0.56 ± 0.90 × 10(5), P = 0.028). HCV proteins could also be detected by IFA in chimera-transfected cells with an obviously low level. Infection assay showed that FL-J6JFH/J4NS5A chimera could produce infectious virus particles, ranging from 10 ± 5 ffu/mL to 78.3 ± 23.6 ffu/mL, while that of FL-J6JFH1 ranged from 5.8 ± 1.5 × 10(2) ffu/mL to 2.5 ± 1.4 × 10(4) ffu/mL. CONCLUSION: JFH1 NS5A might play an important role in the robust replication of J6JFH1. The establishment of FL-J6JFH/J4NS5A provided a useful platform for studying the function of other proteins of HCV.",,"['Wang, Yong-Zhi', 'Wang, Wen-Bo', 'Cao, Ming-Mei', 'Wang, Wen', 'Zhao, Lan-Juan', 'Xu, Gang', 'Ren, Hao', 'Qi, Zhong-Tian']",,,,
,PMC,Recent advances in the molecular biology of metazoan polyamine transport,http://dx.doi.org/10.1007/s00726-011-0987-y,PMC3592336,,,"Very limited molecular knowledge exists about the identity and protein components of the ubiquitous polyamine transporters found in animal cells. However, a number of reports have been published over the last 5 years on potential candidates for metazoan polyamine permeases. We review the available evidence on these putative polyamine permeases, as well as establish a useful «identikit picture» of the general polyamine transport system, based on its properties as found in a wide spectrum of mammalian cells. Any molecular candidate encoding a putative «general» polyamine permease should fit that provided portrait. The current models proposed for the mechanism of polyamine internalization in mammalian cells are also briefly reviewed.",,"['Poulin, R.', 'Casero, R. A.', 'Soulet, D.']",,,,
,PMC,Profiling the Humoral Immune Response of Acute and Chronic Q Fever by Protein Microarray,http://dx.doi.org/10.1074/mcp.M110.006304,PMC3205856,,,"Antigen profiling using comprehensive protein microarrays is a powerful tool for characterizing the humoral immune response to infectious pathogens. Coxiella burnetii is a CDC category B bioterrorist infectious agent with worldwide distribution. In order to assess the antibody repertoire of acute and chronic Q fever patients we have constructed a protein microarray containing 93% of the proteome of Coxiella burnetii, the causative agent of Q fever. Here we report the profile of the IgG and IgM seroreactivity in 25 acute Q fever patients in longitudinal samples. We found that both early and late time points of infection have a very consistent repertoire of IgM and IgG response, with a limited number of proteins undergoing increasing or decreasing seroreactivity. We also probed a large collection of acute and chronic Q fever patient samples and identified serological markers that can differentiate between the two disease states. In this comparative analysis we confirmed the identity of numerous IgG biomarkers of acute infection, identified novel IgG biomarkers for acute and chronic infections, and profiled for the first time the IgM antibody repertoire for both acute and chronic Q fever. Using these results we were able to devise a test that can distinguish acute from chronic Q fever. These results also provide a unique perspective on isotype switch and demonstrate the utility of protein microarrays for simultaneously examining the dynamic humoral immune response against thousands of proteins from a large number of patients. The results presented here identify novel seroreactive antigens for the development of recombinant protein-based diagnostics and subunit vaccines, and provide insight into the development of the antibody response.",,"['Vigil, Adam', 'Chen, Chen', 'Jain, Aarti', 'Nakajima-Sasaki, Rie', 'Jasinskas, Algimantas', 'Pablo, Jozelyn', 'Hendrix, Laura R.', 'Samuel, James E.', 'Felgner, Philip L.']",,,,
,PMC,The ferret as a model organism to study influenza A virus infection,http://dx.doi.org/10.1242/dmm.007823,PMC3180220,21810904,CC BY-NC-SA,"Influenza is a human pathogen that continues to pose a public health threat. The use of small mammalian models has become indispensable for understanding the virulence of influenza viruses. Among numerous species used in the laboratory setting, only the ferret model is equally well suited for studying both the pathogenicity and transmissibility of human and avian influenza viruses. Here, we compare the advantages and limitations of the mouse, ferret and guinea pig models for research with influenza A viruses, emphasizing the multifarious uses of the ferret in the assessment of influenza viruses with pandemic potential. Research performed in the ferret model has provided information, support and guidance for the public health response to influenza viruses in humans. We highlight the recent and emerging uses of this species in influenza virus research that are advancing our understanding of virus-host interactions.",2011 Sep 2,"['Belser, Jessica A.', 'Katz, Jacqueline M.', 'Tumpey, Terrence M.']",Dis Model Mech,,,
,PMC,Properties and Applications of Single-Chain Major Histocompatibility Complex Class I Molecules,http://dx.doi.org/10.1089/ars.2010.3694,PMC3125553,,,"Stable major histocompatibility complex (MHC) class I molecules at the cell surface consist of three separate, noncovalently associated components: the class I heavy chain, the β(2)-microglobulin light chain, and a presented peptide. These three components are assembled inside cells via complex pathways involving many other proteins that have been studied extensively. Correct formation of disulfide bonds in the endoplasmic reticulum is central to this process of MHC class I assembly. For a single specific peptide to be presented at the cell surface for possible immune recognition, between hundreds and thousands of peptide-containing precursor polypeptides are required, so the overall process is relatively inefficient. To increase the efficiency of antigen presentation by MHC class I molecules, and for possible therapeutic purposes, single-chain molecules have been developed in which the three, normally separate components have been joined together via flexible linker sequences in a single polypeptide chain. Remarkably, these single-chain MHC class I molecules fold up correctly, as judged by functional recognition by cells of the immune system, and more recently by X-ray crystallographic structural data. This review focuses on the interesting properties and potential of this new type of engineered MHC class I molecule. Antioxid. Redox Signal. 15, 645–655.",,"['Kotsiou, Eleni', 'Brzostek, Joanna', 'Gould, Keith G.']",,,,
,PMC,Robust substrate profiling method reveals striking differences in specificities of serum and lung fluid proteases,http://dx.doi.org/10.2144/000113717,PMC3159512,,,"Proteases are candidate biomarkers and therapeutic targets for many diseases. Sensitive and robust techniques are needed to quantify proteolytic activities within the complex biological milieu. We hypothesized that a combinatorial protease substrate library could be used effectively to identify similarities and differences between serum and bronchoalveolar lavage fluid (BALF), two body fluids that are clinically important for developing targeted therapies and diagnostics. We used a concise library of fluorogenic probes to map the protease substrate specificities of serum and BALF from guinea pigs. Differences in the proteolytic fingerprints of the two fluids were striking: serum proteases cleaved substrates containing cationic residues and proline, whereas BALF proteases cleaved substrates containing aliphatic and aromatic residues. Notably, cleavage of proline-containing substrates dominated all other protease activities in both human and guinea pig serum. This substrate profiling approach provides a foundation for quantitative comparisons of protease specificities between complex biological samples.",,"['Watson, Douglas S.', 'Jambunathan, Kalyani', 'Askew, David S.', 'Kodukula, Krishna', 'Galande, Amit K.']",,,,
,PMC,"Seroepidemiology of respiratory (group 2) canine coronavirus, canine parainfluenza virus, and Bordetella bronchiseptica infections in urban dogs in a humane shelter and in rural dogs in small communities",,PMC3135029,,,"This prospective study evaluated seroepidemiologic features of canine respiratory coronavirus (CRCoV), canine parainfluenza virus (CPIV), and Bordetella bronchiseptica infections in dogs in an urban humane shelter and in rural/small community dog populations in western Canada. Seroprevalence of CRCoV and CPIV was low compared with other countries; seroprevalence of B. bronchiseptica was moderate to high in most populations examined. Rural dogs were 0.421 times (P ≤ 0.0001) less likely to be positive for CRCoV than dogs admitted to the shelter. There were no statistical differences in prevalence of antibodies to B. bronchiseptica and CPIV between urban and rural populations. Dogs from Fort Resolution, NWT were significantly (P < 0.05) less likely to have moderate or high antibody titers to the 3 agents than dogs in the shelter. Seroconversion to CRCoV was common in dogs in the shelter, but was not associated (P = 0.18) with respiratory disease. Antibodies to CRCoV, CPIV, or B. bronchiseptica on arrival were not significantly (P > 0.05) associated with disease-sparing after entry into the shelter.",,"['Ellis, John', 'Anseeuw, Erika', 'Gow, Sheryl', 'Bryan, Heather', 'Salb, Amanda', 'Goji, Noriko', 'Rhodes, Carrie', 'La Coste, Stacey', 'Smits, Judit', 'Kutz, Susan']",,,,
,PMC,Clinical Applications of DNA Vaccines: Current Progress,http://dx.doi.org/10.1093/cid/cir334,PMC3202319,,,"It was discovered almost 20 years ago that plasmid DNA, when injected into the skin or muscle of mice, could induce immune responses to encoded antigens. Since that time, there has since been much progress in understanding the basic biology behind this deceptively simple vaccine platform and much technological advancement to enhance immune potency. Among these advancements are improved formulations and improved physical methods of delivery, which increase the uptake of vaccine plasmids by cells; optimization of vaccine vectors and encoded antigens; and the development of novel formulations and adjuvants to augment and direct the host immune response. The ability of the current, or second-generation, DNA vaccines to induce more-potent cellular and humoral responses opens up this platform to be examined in both preventative and therapeutic arenas. This review focuses on these advances and discusses both preventive and immunotherapeutic clinical applications.",,"['Ferraro, Bernadette', 'Morrow, Matthew P.', 'Hutnick, Natalie A.', 'Shin, Thomas H.', 'Lucke, Colleen E.', 'Weiner, David B.']",,,,
,PMC,Mechanisms of Protein Retention in the Golgi,http://dx.doi.org/10.1101/cshperspect.a005264,PMC3140682,,,"The protein composition of the Golgi is intimately linked to its structure and function. As the Golgi serves as the major protein-sorting hub for the secretory pathway, it faces the unique challenge of maintaining its protein composition in the face of constant influx and efflux of transient cargo proteins. Much of our understanding of how proteins are retained in the Golgi has come from studies on glycosylation enzymes, largely because of the compartment-specific distributions these proteins display. From these and other studies of Golgi membrane proteins, we now understand that a variety of retention mechanisms are employed, the majority of which involve the dynamic process of iterative rounds of retrograde and anterograde transport. Such mechanisms rely on protein conformation and amino acid-based sorting signals as well as on properties of transmembrane domains and their relationship with the unique lipid composition of the Golgi.",,"Banfield, David K.",,,,
,PMC,Adenoviral Vector Immunity: Its Implications and circumvention strategies,,PMC4009923,,,"Adenoviral (Ad) vectors have emerged as a promising gene delivery platform for a variety of therapeutic and vaccine purposes during last two decades. However, the presence of preexisting Ad immunity and the rapid development of Ad vector immunity still pose significant challenges to the clinical use of these vectors. Innate inflammatory response following Ad vector administration may lead to systemic toxicity, drastically limit vector transduction efficiency and significantly abbreviate the duration of transgene expression. Currently, a number of approaches are being extensively pursued to overcome these drawbacks by strategies that target either the host or the Ad vector. In addition, significant progress has been made in the development of novel Ad vectors based on less prevalent human Ad serotypes and nonhuman Ad. This review provides an update on our current understanding of immune responses to Ad vectors and delineates various approaches for eluding Ad vector immunity. Approaches targeting the host and those targeting the vector are discussed in light of their promises and limitations.",,"['Ahi, Yadvinder S.', 'Bangari, Dinesh S.', 'Mittal, Suresh K.']",,,,
,PMC,Changing Epidemiology of Respiratory Viral Infections in Hematopoietic Cell Transplant Recipients and Solid Organ Transplant Recipients,http://dx.doi.org/10.1097/QCO.0b013e3283480440,PMC3210111,,,"PURPOSE OF REVIEW: New respiratory viruses have been discovered in recent years and new molecular diagnostic assays have been developed that improve our understanding of respiratory virus infections. This article will review the changing epidemiology of these viruses after hematopoietic stem cell and solid organ transplantation. RECENT FINDINGS: Respiratory viruses are frequently detected in transplant recipients. A number of viruses have been newly discovered or emerged in the last decade, including human metapneumovirus, human bocavirus, new human coronaviruses and rhinoviruses, human polyomaviruses, and a new 2009 pandemic strain of influenza A/H1N1. The potential for these viruses to cause lower respiratory tract infections after transplantation varies, and is greatest for human metapneumovirus and H1N1 influenza, but appears to be limited for the other new viruses. Acute and long term complications in hematopoietic and solid organ transplant recipients are active areas of research. SUMMARY: Respiratory viral infections are frequently associated with significant morbidity following transplantation and are therefore of great clinical and epidemiologic interest. As new viruses are discovered, and more sensitive diagnostic methods are developed, defining the full impact of emerging respiratory viruses in transplant recipients must be elucidated by well-designed clinical studies.",,"['Renaud, Christian', 'Campbell, Angela P.']",,,,
,PMC,Viral Life Cycles Captured in Three-Dimensions with Electron Microscopy Tomography,http://dx.doi.org/10.1016/j.coviro.2011.06.008,PMC3163493,,,"Viruses hijack host cell functions and optimize them for viral replication causing a severe threat to human health. However, viruses are also tools to understand cell biology and they may be effective reagents in nano-medicine. Studies from the molecular to cellular levels are aimed at understanding the details of viral life cycles and the underlying virus-host interactions. Recent developments in electron microscopy tomography allow viral and cellular events to be observed in fine structural detail in three-dimension. By combining high-resolution structures of individual proteins and macro-complexes obtained by crystallography and electron cryo-microscopy and image reconstruction with reconstructions performed on sub-tomographic volumes, electron tomography has advanced the structural and mechanistic understanding of virus infections both in vitro and in host cells.",,"['Fu, Chi-yu', 'Johnson, Johnson E.']",,,,
,PMC,Activatable Optical Probes for the Detection of Enzymes,http://dx.doi.org/10.2174/157017911796117232,PMC3601828,,,"The early detection of many human diseases is crucial if they are to be treated successfully. Therefore, the development of imaging techniques that can facilitate early detection of disease is of high importance. Changes in the levels of enzyme expression are known to occur in many diseases, making their accurate detection at low concentrations an area of considerable active research. Activatable fluorescent probes show immense promise in this area. If properly designed they should exhibit no signal until they interact with their target enzyme, reducing the level of background fluorescence and potentially endowing them with greater sensitivity. The mechanisms of fluorescence changes in activatable probes vary. This review aims to survey the field of activatable probes, focusing on their mechanisms of action as well as illustrating some of the in vitro and in vivo settings in which they have been employed.",,"['Drake, Christopher R.', 'Miller, David C.', 'Jones, Ella F.']",,,,
,PMC,Genetic analysis of complex traits in the emerging Collaborative Cross,http://dx.doi.org/10.1101/gr.111310.110,PMC3149489,,,"The Collaborative Cross (CC) is a mouse recombinant inbred strain panel that is being developed as a resource for mammalian systems genetics. Here we describe an experiment that uses partially inbred CC lines to evaluate the genetic properties and utility of this emerging resource. Genome-wide analysis of the incipient strains reveals high genetic diversity, balanced allele frequencies, and dense, evenly distributed recombination sites—all ideal qualities for a systems genetics resource. We map discrete, complex, and biomolecular traits and contrast two quantitative trait locus (QTL) mapping approaches. Analysis based on inferred haplotypes improves power, reduces false discovery, and provides information to identify and prioritize candidate genes that is unique to multifounder crosses like the CC. The number of expression QTLs discovered here exceeds all previous efforts at eQTL mapping in mice, and we map local eQTL at 1-Mb resolution. We demonstrate that the genetic diversity of the CC, which derives from random mixing of eight founder strains, results in high phenotypic diversity and enhances our ability to map causative loci underlying complex disease-related traits.",,"['Aylor, David L.', 'Valdar, William', 'Foulds-Mathes, Wendy', 'Buus, Ryan J.', 'Verdugo, Ricardo A.', 'Baric, Ralph S.', 'Ferris, Martin T.', 'Frelinger, Jeff A.', 'Heise, Mark', 'Frieman, Matt B.', 'Gralinski, Lisa E.', 'Bell, Timothy A.', 'Didion, John D.', 'Hua, Kunjie', 'Nehrenberg, Derrick L.', 'Powell, Christine L.', 'Steigerwalt, Jill', 'Xie, Yuying', 'Kelada, Samir N.P.', 'Collins, Francis S.', 'Yang, Ivana V.', 'Schwartz, David A.', 'Branstetter, Lisa A.', 'Chesler, Elissa J.', 'Miller, Darla R.', 'Spence, Jason', 'Liu, Eric Yi', 'McMillan, Leonard', 'Sarkar, Abhishek', 'Wang, Jeremy', 'Wang, Wei', 'Zhang, Qi', 'Broman, Karl W.', 'Korstanje, Ron', 'Durrant, Caroline', 'Mott, Richard', 'Iraqi, Fuad A.', 'Pomp, Daniel', 'Threadgill, David', 'Pardo-Manuel de Villena, Fernando', 'Churchill, Gary A.']",,,,
,PMC,Dissecting the role of dendritic cells in simian immunodeficiency virus infection and AIDS,http://dx.doi.org/10.1007/s12026-011-8220-3,PMC3140621,,,"Human immunodeficiency virus (HIV) infection is associated with the loss of the two principal types of dendritic cell (DC), myeloid DC (mDC) and plasmacytoid DC (pDC), but the mechanism of this loss and its relationship to AIDS pathogenesis remain ill-defined. The nonhuman primate is a powerful model to dissect this response for several reasons. Both DC subsets have been well characterized in nonhuman primates and shown to have strikingly similar phenotypic and functional characteristics to their counterparts in the human. Moreover, decline of mDC and pDC occurs in rhesus macaques with end-stage simian immunodeficiency virus (SIV) infection, the model of HIV infection in humans. In this brief review, we discuss what is known about DC subsets in pathogenic and nonpathogenic nonhuman primate models of HIV infection and highlight the advances and controversies that currently exist in the field.",,"['Wonderlich, Elizabeth R.', 'Kader, Muhamuda', 'Wijewardana, Viskam', 'Barratt-Boyes, Simon M.']",,,,
,PMC,Poly(C)-Binding Protein 2 Interacts with Sequences Required for Viral Replication in the Hepatitis C Virus (HCV) 5′ Untranslated Region and Directs HCV RNA Replication through Circularizing the Viral Genome,http://dx.doi.org/10.1128/JVI.00339-11,PMC3147998,,,"Sequences in the 5′ untranslated region (5′UTR) of hepatitis C virus (HCV) RNA is important for modulating both translation and RNA replication. The translation of the HCV genome depends on an internal ribosome entry site (IRES) located within the 341-nucleotide 5′UTR, while RNA replication requires a smaller region. A question arises whether the replication and translation functions require different regions of the 5′UTR and different sets of RNA-binding proteins. Here, we showed that the 5′-most 157 nucleotides of HCV RNA is the minimum 5′UTR for RNA replication, and it partially overlaps with the IRES. Stem-loops 1 and 2 of the 5′UTR are essential for RNA replication, whereas stem-loop 1 is not required for translation. We also found that poly(C)-binding protein 2 (PCBP2) bound to the replication region of the 5′UTR and associated with detergent-resistant membrane fractions, which are the sites of the HCV replication complex. The knockdown of PCBP2 by short hairpin RNA decreased the amounts of HCV RNA and nonstructural proteins. Antibody-mediated blocking of PCBP2 reduced HCV RNA replication in vitro, indicating that PCBP2 is directly involved in HCV RNA replication. Furthermore, PCBP2 knockdown reduced IRES-dependent translation preferentially from a dual reporter plasmid, suggesting that PCBP2 also regulated IRES activity. These findings indicate that PCBP2 participates in both HCV RNA replication and translation. Moreover, PCBP2 interacts with HCV 5′- and 3′UTR RNA fragments to form an RNA-protein complex and induces the circularization of HCV RNA, as revealed by electron microscopy. This study thus demonstrates the mechanism of the participation of PCBP2 in HCV translation and replication and provides physical evidence for HCV RNA circularization through 5′- and 3′UTR interaction.",,"['Wang, Linya', 'Jeng, King-Song', 'Lai, Michael M. C.']",,,,
,PMC,A Recombinant Vesicular Stomatitis Virus Bearing a Lethal Mutation in the Glycoprotein Gene Uncovers a Second Site Suppressor That Restores Fusion,http://dx.doi.org/10.1128/JVI.00735-11,PMC3147994,,,"Vesicular stomatitis virus (VSV), a prototype of the Rhabdoviridae family, contains a single surface glycoprotein (G) that is responsible for attachment to cells and mediates membrane fusion. Working with the Indiana serotype of VSV, we employed a reverse genetic approach to produce fully authentic recombinant viral particles bearing lethal mutations in the G gene. By altering the hydrophobicity of the two fusion loops within G, we produced a panel of mutants, W72A, Y73A, Y116A, and A117F, that were nonfusogenic. Propagation of viruses bearing those lethal mutations in G completely depended on complementation by expression of the glycoprotein from the heterologous New Jersey serotype of VSV. The nonfusogenic G proteins oligomerize and are transported normally to the cell surface but fail to mediate acid pH-triggered membrane fusion. The nonfusogenic G proteins also interfered with the ability of wild-type G to mediate fusion, either by formation of mixed trimers or by inhibition of trimer function during fusion. Passage of one recombinant virus, A117F, identified a second site suppressor of the fusion block, E76K. When analyzed in the absence of the A117F substitution, E76K rendered G more sensitive to acid pH-triggered fusion, suggesting that this compensatory mutation is destabilizing. Our work provides a set of authentic recombinant VSV particles bearing lethal mutations in G, confirms that the hydrophobic fusion loops of VSV G protein are critical for membrane fusion, and underscores the importance of the sequence elements surrounding the hydrophobic tips of the fusion loops in driving fusion. This study has implications for understanding dominant targets for inhibition of G-mediated fusion. Moreover, the recombinant viral particles generated here will likely be useful in dissecting the mechanism of G-catalyzed fusion as well as study steps of viral assembly.",,"['Stanifer, Megan L.', 'Cureton, David K.', 'Whelan, Sean P. J.']",,,,
,PMC,The Cytoplasmic Domain of Marburg Virus GP Modulates Early Steps of Viral Infection,http://dx.doi.org/10.1128/JVI.00453-11,PMC3147980,,,"Marburg virus infection is mediated by the only viral surface protein, GP, a trimeric type I transmembrane protein. While its ectodomain mediates receptor binding and fusion of viral and cellular membranes and its transmembrane domain is essential for the recruitment of GP into budding particles by the matrix protein VP40, the role of the short cytoplasmic domain has remained enigmatic. Here we show that a missing cytoplasmic domain did not impair trimerization, intracellular transport, or incorporation of GP into infectious Marburg virus-like particles (iVLPs) but altered the glycosylation pattern as well as the recognition of GP by neutralizing antibodies. These results suggest that subtle conformational changes took place in the ectodomain. To investigate the function of the cytoplasmic domain during viral entry, a novel entry assay was established to monitor the uptake of filamentous VLPs by measuring the occurrence of luciferase-labeled viral nucleocapsids in the cytosol of target cells. This quantitative assay showed that the entry process of VLPs incorporating GP missing its cytoplasmic domain (GPΔCD) was impaired. Supporting these results, iVLPs incorporating a mutant GP missing its cytoplasmic domain were significantly less infectious than iVLPs containing wild-type GP. Taken together, the data indicate that the absence of the short cytoplasmic domain of Marburg virus GP may induce conformational changes in the ectodomain which impact the filoviral entry process.",,"['Mittler, Eva', 'Kolesnikova, Larissa', 'Hartlieb, Bettina', 'Davey, Robert', 'Becker, Stephan']",,,,
,PMC,"Newcastle Disease Virus-Vectored Rabies Vaccine Is Safe, Highly Immunogenic, and Provides Long-Lasting Protection in Dogs and Cats",http://dx.doi.org/10.1128/JVI.00519-11,PMC3147977,,,"Effective, safe, and affordable rabies vaccines are still being sought. Newcastle disease virus (NDV), an avian paramyxovirus, has shown promise as a vaccine vector for mammals. Here, we generated a recombinant avirulent NDV La Sota strain expressing the rabies virus glycoprotein (RVG) and evaluated its potential to serve as a vaccine against rabies. The recombinant virus, rL-RVG, retained its high-growth property in chicken eggs, with titers of up to 10(9.8) 50% egg infective doses (EID(50))/ml of allantoic fluid. RVG expression enabled rL-RVG to spread from cell to cell in a rabies virus-like manner, and RVG was incorporated on the surface of the rL-RVG viral particle. RVG incorporation did not alter the trypsin-dependent infectivity of the NDV vector in mammalian cells. rL-RVG and La Sota NDV showed similar levels of sensitivity to a neutralization antibody against NDV and similar levels of resistance to a neutralization antibody against rabies virus. Animal studies demonstrated that rL-RVG is safe in several species, including cats and dogs, when administered as multiple high doses of recombinant vaccine. Intramuscular vaccination with rL-RVG induced a substantial rabies virus neutralization antibody response and provided complete protection from challenge with circulating rabies virus strains. Most importantly, rL-RVG induced strong and long-lasting protective neutralization antibody responses to rabies virus in dogs and cats. A low vaccine dose of 10(8.3) EID(50) completely protected dogs from challenge with a circulating strain of rabies virus for more than a year. This is the first study to demonstrate that immunization with an NDV-vectored vaccine can induce long-lasting, systemic protective immunity against rabies.",,"['Ge, Jinying', 'Wang, Xijun', 'Tao, Lihong', 'Wen, Zhiyuan', 'Feng, Na', 'Yang, Songtao', 'Xia, Xianzhu', 'Yang, Chinglai', 'Chen, Hualan', 'Bu, Zhigao']",,,,
,PMC,"Nucleolin Interacts with the Feline Calicivirus 3′ Untranslated Region and the Protease-Polymerase NS6 and NS7 Proteins, Playing a Role in Virus Replication",http://dx.doi.org/10.1128/JVI.01878-10,PMC3147956,,,"Cellular proteins play many important roles during the life cycle of all viruses. Specifically, host cell nucleic acid-binding proteins interact with viral components of positive-stranded RNA viruses and regulate viral translation, as well as RNA replication. Here, we report that nucleolin, a ubiquitous multifunctional nucleolar shuttling phosphoprotein, interacts with the Norwalk virus and feline calicivirus (FCV) genomic 3′ untranslated regions (UTRs). Nucleolin can also form a complex in vitro with recombinant Norwalk virus NS6 and -7 (NS6/7) and can be copurified with the analogous protein from feline calicivirus (p76 or NS6/7) from infected feline kidney cells. Nucleolin RNA levels or protein were not modified during FCV infection; however, as a consequence of the infection, nucleolin was seen to relocalize from the nucleoli to the nucleoplasm, as well as to the perinuclear area where it colocalizes with the feline calicivirus NS6/7 protein. In addition, antibodies to nucleolin were able to precipitate viral RNA from feline calicivirus-infected cells, indicating a direct or indirect association of nucleolin with the viral RNA during virus replication. Small interfering RNA (siRNA)-mediated knockdown of nucleolin resulted in a reduction of the cytopathic effect and virus yield in CrFK cells. Taken together, these results demonstrate that nucleolin is a nucleolar component that interacts with viral RNA and NS6/7 and is required for feline calicivirus replication.",,"['Cancio-Lonches, Clotilde', 'Yocupicio-Monroy, Martha', 'Sandoval-Jaime, Carlos', 'Galvan-Mendoza, Iván', 'Ureña, Luis', 'Vashist, Surender', 'Goodfellow, Ian', 'Salas-Benito, Juan', 'Gutiérrez-Escolano, Ana Lorena']",,,,
,PMC,A Tyrosine-Sulfated CCR5-Mimetic Peptide Promotes Conformational Transitions in the HIV-1 Envelope Glycoprotein,http://dx.doi.org/10.1128/JVI.00630-11,PMC3147930,,,"The HIV-1 envelope glycoprotein is a trimeric complex of heterodimers composed of a surface glycoprotein, gp120, and a transmembrane component, gp41. The association of this complex with CD4 stabilizes the coreceptor-binding site of gp120 and promotes the exposure of the gp41 helical region 1 (HR1). Here, we show that a 15-amino-acid peptide mimetic of the HIV-1 coreceptor CCR5 fused to a dimeric antibody Fc domain (CCR5mim-Ig) bound two gp120 molecules per envelope glycoprotein complex and by itself promoted HR1 exposure. CCR5mim-Ig also stabilized the association of a CD4-mimetic peptide with the envelope glycoprotein. A fusion of the CD4- and CCR5-mimetic peptides, DM1, bound gp120 and neutralized R5, R5X4, and X4 HIV-1 isolates comparably to CD4, and they did so markedly more efficiently than either peptide alone. Our data indicate that the potency of DM1-Ig derives from its avidity for the HIV-1 envelope glycoprotein trimer and from the bidirectional induction of its receptor-mimetic components. DM1 has significant advantages over other inhibitors that target both coreceptor and CD4-binding sites, and it may serve as a lead for a new class of HIV-1 inhibitor peptides.",,"['Kwong, Jo Ann', 'Dorfman, Tatyana', 'Quinlan, Brian D.', 'Chiang, Jessica J.', 'Ahmed, Asim A.', 'Choe, Hyeryun', 'Farzan, Michael']",,,,
,PMC,Role of Proteases in the Release of Porcine Epidemic Diarrhea Virus from Infected Cells,http://dx.doi.org/10.1128/JVI.00464-11,PMC3147927,,,"Porcine epidemic diarrhea virus (PEDV), a causative agent of pig diarrhea, requires a protease(s) for multicycle replication in cultured cells. However, the potential role of proteases in the infection process remains unclear. In order to explore this, we used two different approaches: we infected either Vero cells in the presence of trypsin or Vero cells that constitutively express the membrane-associated protease TMPRSS2 (Vero/TMPRSS2 cells). We found that PEDV infection was enhanced, and viruses were efficiently released into the culture fluid, from Vero cells infected in the presence of protease, while in cells without protease, the virus grew, but its release into the culture fluid was strongly hampered. Cell-to-cell fusion of PEDV-infected cells and cleavage of the spike (S) protein were observed in cells with protease. When infected Vero cells were cultured for 3 days in the absence of trypsin but were then treated transiently with trypsin, infectious viruses were immediately released from infected cells. In addition, treatment of infected Vero/TMPRSS2 cells with the protease inhibitor leupeptin strongly blocked the release of virus into the culture fluid. Under electron microscopy, PEDV-infected Vero cells, as well as PEDV-infected Vero/TMPRSS2 cells treated with leupeptin, retained huge clusters of virions on their surfaces, while such clusters were rarely seen in the presence of trypsin and the absence of leupeptin in Vero and Vero/TMPRSS2 cells, respectively. Thus, the present study indicates that proteases play an important role in the release of PEDV virions clustered on cells after replication occurs. This unique observation in coronavirus infection suggests that the actions of proteases are reminiscent of that of the influenza virus neuraminidase protein.",,"['Shirato, Kazuya', 'Matsuyama, Shutoku', 'Ujike, Makoto', 'Taguchi, Fumihiro']",,,,
,PMC,Molecular Epidemiology and Phylogeny Reveal Complex Spatial Dynamics in Areas Where Canine Parvovirus Is Endemic,http://dx.doi.org/10.1128/JVI.01576-10,PMC3147911,,,"Canine parvovirus type 2 (CPV-2) is a severe enteric pathogen of dogs, causing high mortality in unvaccinated dogs. After emerging, CPV-2 spread rapidly worldwide. However, there is now some evidence to suggest that international transmission appears to be more restricted. In order to investigate the transmission and evolution of CPV-2 both nationally and in relation to the global situation, we have used a long-range PCR to amplify and sequence the full VP2 gene of 150 canine parvoviruses obtained from a large cross-sectional sample of dogs presenting with severe diarrhea to veterinarians in the United Kingdom, over a 2-year period. Among these 150 strains, 50 different DNA sequence types (S) were identified, and apart from one case, all appeared unique to the United Kingdom. Phylogenetic analysis provided clear evidence for spatial clustering at the international level and for the first time also at the national level, with the geographical range of some sequence types appearing to be highly restricted within the United Kingdom. Evolution of the VP2 gene in this data set was associated with a lack of positive selection. In addition, the majority of predicted amino acid sequences were identical to those found elsewhere in the world, suggesting that CPV VP2 has evolved a highly fit conformation. Based on typing systems using key amino acid mutations, 43% of viruses were CPV-2a, and 57% CPV-2b, with no type 2 or 2c found. However, phylogenetic analysis suggested complex antigenic evolution of this virus, with both type 2a and 2b viruses appearing polyphyletic. As such, typing based on specific amino acid mutations may not reflect the true epidemiology of this virus. The geographical restriction that we observed both within the United Kingdom and between the United Kingdom and other countries, together with the lack of CPV-2c in this population, strongly suggests the spread of CPV within its population may be heterogeneously subject to limiting factors. This cross-sectional study of national and global CPV phylogeographic segregation reveals a substantially more complex epidemic structure than previously described.",,"['Clegg, S. R.', 'Coyne, K. P.', 'Parker, J.', 'Dawson, S.', 'Godsall, S. A.', 'Pinchbeck, G.', 'Cripps, P. J.', 'Gaskell, R. M.', 'Radford, A. D.']",,,,
,PMC,Clinical Outcome of Henipavirus Infection in Hamsters Is Determined by the Route and Dose of Infection,http://dx.doi.org/10.1128/JVI.00473-11,PMC3147900,,,"Nipah virus (NiV) and Hendra virus (HeV) are emerging zoonotic viruses and the causative agents of severe respiratory disease and encephalitis in humans. Little is known about the mechanisms that govern the development of respiratory and neurological disease. Using a hamster model of lethal NiV and HeV infection, we describe the role of the route and dose of infection on the clinical outcome and determine virus tropism and host responses following infection. Infection of hamster with a high dose of NiV or HeV resulted in acute respiratory distress. NiV initially replicated in the upper respiratory tract epithelium, whereas HeV initiated infection primarily in the interstitium. In contrast, infection with a low dose of NiV or HeV resulted in the development of neurological signs and more systemic spread of the virus through involvement of the endothelium. The development of neurological signs coincided with disruption of the blood-brain barrier (BBB) and expression of tumor necrosis alpha (TNF-α) and interleukin 1 β (IL-1β). In addition, interferon-inducible protein 10 (IP-10) was identified as playing an important role in NiV and HeV pathogenesis. These studies reveal novel information on the development and progression of NiV and HeV clinical disease, provide a mechanism for the differences in transmission observed between NiV and HeV outbreaks, and identify specific cytokines and chemokines that serve as important targets for treatment.",,"['Rockx, Barry', 'Brining, Douglas', 'Kramer, Joshua', 'Callison, Julie', 'Ebihara, Hideki', 'Mansfield, Keith', 'Feldmann, Heinz']",,,,
,PMC,Importin α-Mediated Nuclear Import of Cytoplasmic Poly(A) Binding Protein Occurs as a Direct Consequence of Cytoplasmic mRNA Depletion,http://dx.doi.org/10.1128/MCB.05402-11,PMC3147611,,,"Recent studies have found the cytoplasmic poly(A) binding protein (PABPC) to have opposing effects on gene expression when concentrated in the cytoplasm versus in the nucleus. PABPC is predominantly cytoplasmic at steady state, where it enhances protein synthesis through simultaneous interactions with mRNA and translation factors. However, it accumulates dramatically within the nucleus in response to various pathogenic and nonpathogenic stresses, leading to an inhibition of mRNA export. The molecular events that trigger relocalization of PABPC and the mechanisms by which it translocates into the nucleus to block gene expression are not understood. Here, we reveal an RNA-based mechanism of retaining PABPC in the cytoplasm. Expression either of viral proteins that promote mRNA turnover or of a cytoplasmic deadenylase drives nuclear relocalization of PABPC in a manner dependent on the PABPC RNA recognition motifs (RRMs). Using multiple independent binding sites within its RRMs, PABPC interacts with importin α, a component of the classical import pathway. Finally, we demonstrate that the direct association of PABPC with importin α is antagonized by the presence of poly(A) RNA, supporting a model in which RNA binding masks nuclear import signals within the PABPC RRMs, thereby ensuring efficient cytoplasmic retention of this protein in normal cells. These findings further suggest that cells must carefully calibrate the ratio of PABPC to mRNA, as events that offset this balance can dramatically influence gene expression.",,"['Kumar, G. Renuka', 'Shum, Leona', 'Glaunsinger, Britt A.']",,,,
,PMC,In vivo expression profile of the antiviral restriction factor and tumor-targeting antigen CD317/BST-2/HM1.24/tetherin in humans,http://dx.doi.org/10.1073/pnas.1101684108,PMC3158195,,,"Human CD317 is an intrinsic immunity factor that restricts the release of enveloped viruses, including the major pathogens HIV and Lassa virus, from infected cells in culture. Its importance for infection control in humans is unclear, due in part to its incompletely defined in vivo expression pattern. CD317 also has been proposed as a selective target for immunotherapy of multiple myeloma. To provide a framework for studies of the biological functions, regulation, and therapeutic potential of CD317, we performed microarray-based expression profiling in 468 tissue samples from 25 healthy organs from more than 210 patients. We found that CD317 protein was expressed to varying degrees in all organs tested and detected in a number of specialized cell types, including hepatocytes, pneumocytes, ducts of major salivary glands, pancreas and kidney, Paneth cells, epithelia, Leydig cells, plasma cells, bone marrow stromal cells, monocytes, and vascular endothelium. Although many of these cell types are in vivo targets for pathogenic viruses, restriction by CD317 or virus-encoded antagonists has been documented in only some of them. Limited cell type–dependent coexpression of CD317 with the IFN biomarker MxA in vivo and lack of responsive stimulation in organ explants suggest that interferons may only partially regulate CD317. This in vivo expression profiling sheds light on the biology and species-specificity of CD317, identifies multiple thus far unknown interaction sites of viruses with this restriction factor, and refutes the concept of its restricted constitutive expression and primary IFN inducibility. CD317's widespread expression calls into question its suitability as a target for immunotherapy.",,"['Erikson, Elina', 'Adam, Tarek', 'Schmidt, Sarah', 'Lehmann-Koch, Judith', 'Over, Benjamin', 'Goffinet, Christine', 'Harter, Christoph', 'Bekeredjian-Ding, Isabelle', 'Sertel, Serkan', 'Lasitschka, Felix', 'Keppler, Oliver T.']",,,,
,PMC,Transferrin receptor 1 in the zoonosis and pathogenesis of New World hemorrhagic fever arenaviruses,http://dx.doi.org/10.1016/j.mib.2011.07.014,PMC3159852,,,"At least five New World arenaviruses cause severe human hemorrhagic fevers. These viruses are transmitted to humans through contact with their respective South American rodent hosts. Each uses human transferrin receptor 1 (TfR1) as its obligate receptor. Accidental similarities between human TfR1 and TfR1 orthologs of arenviral host species enable zoonoses, whereas mice and rats are not infectable because they lack these TfR1 determinants of infection. All pathogenic New World arenaviruses bind to a common region of the apical domain of TfR1. The ability of a New World arenavirus to use human TfR1 is absolutely predictive of its ability to cause hemorrhagic fevers in humans. Non-pathogenic arenaviruses, closely related to hemorrhagic fever arenaviruses, cannot utilize human TfR1 but efficiently enter cells through TfR1 orthologs of their native rodent hosts. Mutagenesis studies suggest that minor changes in the entry glycoproteins of these non-pathogenic viruses may allow human transmission. TfR1 is upregulated as a result of iron sequestration during the acute phase response to infection, and the severity of disease may result from amplification of viral replication during this response.",,"['Choe, Hyeryun', 'Jemielity, Stephanie', 'Abraham, Jonathan', 'Radoshitzky, Sheli R.', 'Farzan, Michael']",,,,
,PMC,CXCL10/IP-10 in Infectious Diseases Pathogenesis and Potential Therapeutic Implications,http://dx.doi.org/10.1016/j.cytogfr.2011.06.001,PMC3203691,,,"C-X-C motif chemokine 10 (CXCL10) also known as interferon γ-induced protein 10 kDa (IP-10) or small-inducible cytokine B10 is a cytokine belonging to the CXC chemokine family. CXCL10 binds CXCR3 receptor to induce chemotaxis, apoptosis, cell growth and angiostasis. Alterations in CXCL10 expression levels have been associated with inflammatory diseases including infectious diseases, immune dysfunction and tumor development. CXCL10 is also recognized as a biomarker that predicts severity of various diseases. A review of the emerging role of CXCL10 in pathogenesis of infectious diseases revealed diverse roles of CXCL10 in disease initiation and progression. The potential utilization of CXCL10 as a therapeutic target for infectious diseases is discussed.",,"['Liu, Mingli', 'Guo, Shanchun', 'Hibbert, Jacqueline M.', 'Jain, Vidhan', 'Singh, Neeru', 'Wilson, Nana O.', 'Stiles, Jonathan K.']",,,,
,PMC,"MMP9 deficiency does not decrease blood brain barrier disruption, but increases astrocyte MMP3 expression during viral encephalomyelitis",http://dx.doi.org/10.1002/glia.21222,PMC3174277,,,"Expression of matrix metalloproteinases (MMPs), especially MMP9 correlates with blood brain barrier (BBB) disruption during many neuroinflammatory diseases. During neurotropic coronavirus virus (JHMV) induced encephalomyelitis, MMP9 activity is restricted to neutrophils. Furthermore, myeloid cell depletion implicated MMP9 in facilitating leukocyte central nervous system (CNS) infiltration via loss of BBB integrity. The requirement of MMP9 in BBB disruption was thus assessed in JHMV infected MMP9 deficient (MMP9(−/−)) mice. Depletion of neutrophils reduced CNS accumulation of monocytes and T cells, albeit without affecting overall pathogenesis. By contrast, infected MMP9(−/−) mice revealed no differences in CNS leukocyte infiltration, composition or localization, consistent with BBB disruption similar to wild type (WT) mice. Unimpaired T cell mediated virus control supported an unexpectedly redundant role of MMP9 in promoting leukocyte access to the brain parenchyma. While MMP9 deficiency did not expand the overall limited pattern of MMP expression during JHMV infection, it coincided with MMP3 upregulation. MMP3 expression remained largely confined to astrocytes, similar to WT mice. These data demonstrate that neutrophil-derived MMP9 is not the sole mediator facilitating parenchymal leukocyte entry via BBB disruption during viral encephalomyelitis. Moreover, significantly enhanced MMP3 expression by astrocytes in infected MMP9(−/−) mice suggests an active role of resident cells in participating and potentially collaborating with infiltrating cells in regulating BBB permeability. Overall, these results highlight the complexity of targeting individual MMPs as a strategy to regulate inflammation.",,"['Savarin, Carine', 'Stohlman, Stephen A.', 'Rietsch, Anna M.', 'Butchi, Niranjan', 'Ransohoff, Richard M.', 'Bergmann, Cornelia C.']",,,,
,PMC,Microbial Genomics and Infectious Diseases,http://dx.doi.org/10.1056/NEJMra1003071,PMC3412127,,,,,"Relman, David A.",,,,
,PMC,Inhibitors of SARS-CoV Entry - Identification using an Internally-Controlled Dual Envelope Pseudovirion Assay,http://dx.doi.org/10.1016/j.antiviral.2011.07.016,PMC3205982,,,"Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged as the causal agent of an endemic atypical pneumonia, infecting thousands of people worldwide. Although a number of promising potential vaccines and therapeutic agents for SARS-CoV have been described, no effective antiviral drug against SARS-CoV is currently available. The intricate, sequential nature of the viral entry process provides multiple valid targets for drug development. Here, we describe a rapid and safe cell-based high-throughput screening system, Dual Envelope Pseudovirion (DEP) Assay, for specifically screening inhibitors of viral entry. The assay system employs a novel dual envelope strategy, using lentiviral pseudovirions as targets whose entry is driven by the SARS-CoV Spike glycoprotein. A second, unrelated viral envelope is used as an internal control to reduce the number of false positives. As an example of the power of this assay a class of inhibitors is reported with the potential to inhibit SARS-CoV at two steps of the replication cycle, viral entry and particle assembly. This assay system can be easily adapted to screen entry inhibitors against other viruses with the careful selection of matching partner virus envelopes.",,"['Zhou, Yanchen', 'Agudelo, Juliet', 'Lu, Kai', 'Goetz, David H.', 'Hansell, Elizabeth', 'Chen, Yen Ting', 'Roush, William R.', 'McKerrow, James', 'Craik, Charles S.', 'Amberg, Sean M.', 'Simmons, Graham']",,,,
,PMC,Efficient induction of a Her2-specific anti-tumor response by dendritic cells pulsed with a Hsp70L1–Her2(341–456) fusion protein,http://dx.doi.org/10.1038/cmi.2011.21,PMC4012883,,,"Heat shock proteins (HSPs) have been shown to interact with antigen-presenting cells (APCs), especially dendritic cells (DCs). HSPs act as potent adjuvants, inducing a Th1 response, as well as antigen-specific CD8(+) cytotoxic T lymphocytes (CTL) via cross-presentation. Our previous work has demonstrated that Hsp70-like protein 1 (Hsp70L1), a new member of the Hsp70 subfamily, can act as a powerful Th1 adjuvant in a DC-based vaccine. Here we report the efficient induction of tumor antigen-specific T cell immune response by DCs pulsed with recombinant fusion protein of Hsp70L1 and Her2(341–456), the latter of which is a fragment of Her2/neu (Her2) containing E75 (a HLA-A2 restricted CTL epitope). The fusion protein Hsp70L1–Her2(341–456) promotes the maturation of DCs and activates them to produce cytokines, such as IL-12 and TNF-α, and chemokines, such as MIP-1α, MIP-1β and RANTES. Taken together, these results indicate that the adjuvant activity of Hsp70L1 is maintained in the fusion protein. Her2-specific HLA-A2.1-restricted CD8(+) CTLs can be generated efficiently either from the Peripheral blood lymphocytes (PBL) of healthy donors or from the splenocytes of immunized HLA-A2.1/K(b) transgenic mice by in vitro stimulation or immunization with DCs pulsed with the Hsp70L1–Her2(341–456) fusion protein. This results in more potent target cell killing in an antigen-specific and HLA-A2.1-restricted manner. Adoptive transfer of splenocytes from transgenic mice immunized with Hsp70L1–Her2(341–456)-pulsed DCs can markedly inhibit tumor growth and prolong the survival of nude mice with Her2(+)/HLA-A2.1(+) human carcinomas. These results suggest that Hsp70L1–Her2(341–456)-pulsed DCs could be a new therapeutic vaccine for patients with Her2(+) cancer.",,"['Fu, Qiang', 'Wu, Yanfeng', 'Yan, Fang', 'Wang, Ning', 'Wang, Wenying', 'Cao, Xuetao', 'Wang, Yajie', 'Wan, Tao']",,,,
,PMC,Rat Ace allele variation determines susceptibility to AngII induced renal damage,http://dx.doi.org/10.1177/1470320311415886,PMC3356861,,,"INTRODUCTION: Ace b/l polymorphism in rat is associated to differential tissue ACE expression and activity, and susceptibility to renal damage. Same polymorphism was recently found in outbred Wistar rat strain with b allele accounting for higher renal ACE, and provided a model for studying RAAS response behind the innate high or low ACE conditions. METHODS: We investigated the reaction of these alleles on chronic Angiotensin II (AngII) infusion. Wistar rats were selected to breed male homozygotes for the b (WU-B) or l allele (WU-L) (n=12). For each allele, one group (n=6) received AngII infusion via osmotic minipump (435 ng/kg/min) for three weeks. Other group (n=6) served as control. RESULTS: WU-B had higher ACE activity at baseline then WU-L. Interestingly, baseline renal ACE2 expression and activity were higher in WU-L. AngII infusion induced same increase in blood pressure in both genotypes, no proteinuria, but caused tubulo-interstitial renal damage with increased α-SMA and monocyte/macrophage influx only in WU-B (p<0.05). Low ACE WU-L rats did not develop renal damage. CONCLUSION: AngII infusion causes proteinuria independent renal damage only in rats with genetically predetermined high ACE while rats with low ACE seemed to be protected against the detrimental effect of AngII. Differences in renal ACE2, mirroring those in ACE, might be involved.",,"['Kamilic, Jelena', 'Hamming, Inge', 'Lely, A. Titia', 'Korstanje, Ron', 'Schulze, Ute', 'Poppinga, Wilfred J.', 'Turner, Anthony J.', 'Clarke, Nicola E.', 'van Goor, Harry', 'Navis, Gerjan J.']",,,,
,PMC,Fever in the Returning International Traveller Initial Assessment Guidelines: Committee to Advise on Tropical Medicine and Travel (CATMAT),http://dx.doi.org/10.14745/ccdr.v37i00a03,PMC6802436,,,,,"['Boggild, A.', 'Ghesquiere, Dr. W.', 'McCarthy, Dr. A.', None]",,,,
,PMC,TGF‐β1 serum concentration as a complementary diagnostic biomarker of lung cancer: establishment of a cut‐point value,http://dx.doi.org/10.1002/jcla.20465,PMC6647734,,,"Lung cancer is a malignant disease with increasing mortality rates. Cytokines play a role in normal cell growth regulation and differentiation and are also implicated in malignant disease. Among these cytokines, Transforming Growth Factor β type 1 (TGF‐β1) acts as a tumor promoter in malignant cells. Several clinical studies have found high levels of TGF‐β1 in various cancer types. The aim of this study was to establish a TGF‐β1 cut‐off point as a complementary diagnostic tool in lung cancer detection. Therefore, 72 clinically well‐characterized individuals were studied, 41 lung cancer patients and 31 healthy subjects. Serum TGF‐β1 concentration was measured by an enzyme‐linked immunosorbent assay (ELISA). We compared statistically the serum TGF‐β1 concentration between both groups with analysis of variance, linear regression and receiver operating curve analysis. We observed that lung cancer patients produced higher TGF‐β1 levels than healthy individuals (37,225±9,436 vs. 28,416±9,324 pg/ml, P<0.001). The cut‐point diagnostic value was 30,500 pg/ml with 80.5% sensitivity, 64.5% specificity and odds ratio: 7.5, 95% CI: 2.6–21.8. Conclusions: We found significantly higher TGF‐β1 levels in lung cancer patients than in healthy individuals. We propose the measurement of serum TGF‐β1 levels as a complementary diagnostic test in lung cancer detection. J. Clin. Lab. Anal. 25:238–243, 2011. © 2011 Wiley‐Liss, Inc.",,"['González‐Santiago, Ana E.', 'Mendoza‐Topete, Luz A.', 'Sánchez‐Llamas, Francisco', 'Troyo‐Sanromán, Rogelio', 'Gurrola‐Díaz, Carmen M.']",,,,
,PMC,Plasmacytoid dendritic cells: one-trick ponies or workhorses of the immune system?,http://dx.doi.org/10.1038/nri3027,PMC4157822,,,"Plasmacytoid dendritic cells (pDCs) were first described as interferon-producing cells and, for many years, their overlapping characteristics with both lymphocytes and classical dendritic cells (cDCs) created confusion over their exact ontogeny. In this Viewpoint article, Nature Reviews Immunology asks five leaders in the field to discuss their thoughts on the development and functions of pDCs — do these cells serve mainly as a major source of type I interferons or do they also make other important contributions to immune responses?",,"['Reizis, Boris', 'Colonna, Marco', 'Trinchieri, Giorgio', 'Barrat, Franck', 'Gilliet, Michel']",,,,
,PMC,Recent advances in the role of non-invasive ventilation in acute respiratory failure,http://dx.doi.org/10.1016/S0377-1237(11)60034-8,PMC4920747,,,"Non-invasive positive pressure ventilation (NIPPV) is the technique of delivering mechanical ventilation without endotracheal intubation or tracheostomy. This is increasingly being utilised in both acute and chronic conditions. Strong evidence supports the use of NIPPV for acute respiratory failure (ARF) to prevent endotracheal intubation (ETI) and to facilitate extubation in patients with acute exacerbations of chronic obstructive pulmonary disease, to avoid ETI in acute cardiogenic pulmonary oedema (ACPO), and in immunocompromised patients. Weaker evidence supports the use of NIPPV for patients with ARF due to asthma exacerbations, with postoperative ARF, pneumonia and acute lung injury/acute respiratory distress syndrome. NIPPV should be applied under close monitoring for signs of treatment failure and, in such cases, ETI should be promptly available. A trained team, at an appropriate location, with careful patient selection and optimal choice of devices can optimise the outcome of NIPPV.",,"['Bhattacharyya, D', 'Prasad, BNBM', 'Rajput, AK']",,,,
,PMC,Synthesis of 4′-Ethynyl-2′-deoxy-4′-thioribonucleosides and Discovery of a Highly Potent and Less Toxic NRTI,http://dx.doi.org/10.1021/ml2001054,PMC3686520,,,"[Image: see text] The synthesis of 4′-ethynyl-2′-deoxy-4′-thioribonucleosides was carried out utilizing an electrophilic glycosidation in which 4-ethynyl-4-thiofuranoid glycal 16 served as a glycosyl donor. Electrophilic glycosidation between 16 and the silylated nucleobases (N(4)-acetylcytosine, N(6)-benzoyladenine, and N(2)-acetyl-O(6)-diphenylcarbamoylguanine) was carried out in the presence of N-iodosuccinimide (NIS), leading to the exclusive formation of the desired β-anomers 29, 33, and 36. Anti-HIV studies demonstrated that these 4′-thio nucleosides were less cytotoxic to T-lymphocyte (i.e., MT-4 cells) than the corresponding 4′-ethynyl derivatives of 2′-deoxycytidine (44), 2′-deoxyadenosine (45), and 2′-deoxyguanosine (46). Comparison of the selectivity indices (SI) was made between 4′-thionucleosides (32, 41, and 43) and the corresponding 4′-oxygen analogues 44-46 by using the reported CC(50) and EC(50) values. In the case of cytosine and adenine nucleosides, comparable SI values were obtained as follows: 32 (545) and 44 (458); 41 (>230) and 45 (1630). In contrast, 4′-ethynyl-2′-deoxy-4′-thioguanosine 43 was found to possess a SI value of >18200, which is 20 times better than that of 46 (933).",,"['Haraguchi, Kazuhiro', 'Shimada, Hisashi', 'Kimura, Keigo', 'Akutsu, Genta', 'Tanaka, Hiromichi', 'Abe, Hiroshi', 'Hamasaki, Takayuki', 'Baba, Masanori', 'Gullen, Elizabeth A.', 'Dutschman, Ginger E.', 'Cheng, Yung-Chi', 'Balzarini, Jan']",,,,
,PMC,Incorporating individual health-protective decisions into disease transmission models: a mathematical framework,http://dx.doi.org/10.1098/rsif.2011.0325,PMC3262418,,,"It is anticipated that the next generation of computational epidemic models will simulate both infectious disease transmission and dynamic human behaviour change. Individual agents within a simulation will not only infect one another, but will also have situational awareness and a decision algorithm that enables them to modify their behaviour. This paper develops such a model of behavioural response, presenting a mathematical interpretation of a well-known psychological model of individual decision making, the health belief model, suitable for incorporation within an agent-based disease-transmission model. We formalize the health belief model and demonstrate its application in modelling the prevalence of facemask use observed over the course of the 2003 Hong Kong SARS epidemic, a well-documented example of behaviour change in response to a disease outbreak.",,"['Durham, David P.', 'Casman, Elizabeth A.']",,,,
,PMC,Association of Human bocavirus with Respiratory Infections in Outpatients and in Patients Attended at a Reference Hospital,http://dx.doi.org/10.1007/s13337-011-0042-3,PMC3550741,,,"The role of Human bocavirus (HBoV) in human infectious disease is unclear due to the frequent detection of this virus in association with other respiratory viruses with a recognized pathogenic role in acute respiratory infection. We have analyzed the impact of HBoV in outpatients and in patients requiring hospitalisation or emergency attention for acute respiratory infections. Respiratory viruses were investigated by real-time PCR, direct antigen detection and/or viral culture by shell-vial assay. Nasopharyngeal aspirates, BAL and/or sputum samples from patients attended at a reference hospital, and nasal/throat swabs from outpatients were used. Respiratory viruses were detected in 660 samples (47%). HBoV detection rate was 12.6%, only preceded by respiratory syncytial virus (25%). Co-detections were observed in 12.9% of samples, and HBoV was present in 81% of them. Similar detection rates of HBoV were obtained in individuals with positive and negative results for other respiratory viruses (12.5% and 12.7%, respectively). The crossing point value was taken as a measure of HBoV viral load. Higher HBoV loads were observed in children, and in patients from the hospital. HBoV viral load was not associated with symptoms of upper respiratory tract infection or lower respiratory tract disease. Although HBoV is frequently detected in respiratory specimens, there is a poor association between HBoV-positive specimens and clinical parameters. A clinical impact of HBoV in respiratory infection probably occurs in few cases.",,"['Pedrosa-Corral, Irene', 'Pérez-Ruiz, Mercedes', 'Navarro-Marí, José-María', 'Ruiz-Bravo, Alfonso']",,,,
,PMC,"Transocular Entry of Seasonal Influenza–Attenuated Virus Aerosols and the Efficacy of N95 Respirators, Surgical Masks, and Eye Protection in Humans",http://dx.doi.org/10.1093/infdis/jir238,PMC3164472,,,"Background. The efficacy of barrier precautions to prevent influenza transmission is unknown. Methods. Twenty-eight participants were exposed to monodispersed live attenuated influenza vaccine (LAIV) particles (4.9 μm) in 6 groups: group 1, no precautions; group 2, ocular exposure only; group 3, surgical mask without eye protection; group 4, surgical mask with eye protection; group 5, fit-tested N95 respirator without eye protection; and group 6, fit-tested N95 respirator with eye protection. Influenza was detected by reverse-transcription polymerase chain reaction (RT-PCR) and culture in nasal washes. Exact 95% confidence intervals (CIs) were calculated. Results. Influenza was detected in 4 of 4 participants in group 1 (95% CI, 0–.60), 3 of 4 in group 2 (95% CI, .006–.806]), 5 of 5 in group 3 (95% CI, 0–.522), 5 of 5 in group 4, (95% CI, 0–.522), 3 of 5 in group 5 (95% CI, .053–.853), and 1 of 5 in group 6 (95% CI, .05–.72). RT-PCR revealed significant differences between group 1 and all other groups except group 3. Conclusions. Transocular transmission of LAIV occured in most participants suggesting the necessity of eye protection. An N95 respirator provided the best guard further enhanced by eye protection.",,"['Bischoff, Werner E.', 'Reid, Tanya', 'Russell, Gregory B.', 'Peters, Timothy R.']",,,,
,PMC,Molecular Detection of Bacterial Pathogens Using Microparticle Enhanced Double-Stranded DNA Probes,http://dx.doi.org/10.1021/ac2012575,PMC4104485,,,"[Image: see text] Rapid, specific, and sensitive detection of bacterial pathogens is essential toward clinical management of infectious diseases. Traditional approaches for pathogen detection, however, often require time-intensive bacterial culture and amplification procedures. Herein, a microparticle enhanced double-stranded DNA probe is demonstrated for rapid species-specific detection of bacterial 16S rRNA. In this molecular assay, the binding of the target sequence to the fluorophore conjugated probe thermodynamically displaces the quencher probe and allows the fluorophore to fluoresce. By incorporation of streptavidin-coated microparticles to localize the biotinylated probes, the sensitivity of the assay can be improved by 3 orders of magnitude. The limit of detection of the assay is as few as eight bacteria without target amplification and is highly specific against other common pathogens. Its applicability toward clinical diagnostics is demonstrated by directly identifying bacterial pathogens in urine samples from patients with urinary tract infections.",,"['Riahi, Reza', 'Mach, Kathleen E.', 'Mohan, Ruchika', 'Liao, Joseph C.', 'Wong, Pak Kin']",,,,
,PMC,Ex vivo characterization and isolation of rare memory B cells with antigen tetramers,http://dx.doi.org/10.1182/blood-2011-03-341917,PMC3138687,,,"Studying human antigen-specific memory B cells has been challenging because of low frequencies in peripheral blood, slow proliferation, and lack of antibody secretion. Therefore, most studies have relied on conversion of memory B cells into antibody-secreting cells by in vitro culture. To facilitate direct ex vivo isolation, we generated fluorescent antigen tetramers for characterization of memory B cells by using tetanus toxoid as a model antigen. Brightly labeled memory B cells were identified even 4 years after last immunization, despite low frequencies ranging from 0.01% to 0.11% of class-switched memory B cells. A direct comparison of monomeric to tetrameric antigen labeling demonstrated that a substantial fraction of the B-cell repertoire can be missed when monomeric antigens are used. The specificity of the method was confirmed by antibody reconstruction from single-cell sorted tetramer(+) B cells with single-cell RT-PCR of the B-cell receptor. All antibodies bound to tetanus antigen with high affinity, ranging from 0.23 to 2.2 nM. Furthermore, sequence analysis identified related memory B cell and plasmablast clones isolated more than a year apart. Therefore, antigen tetramers enable specific and sensitive ex vivo characterization of rare memory B cells as well as the production of fully human antibodies.",,"['Franz, Bettina', 'May, Kenneth F.', 'Dranoff, Glenn', 'Wucherpfennig, Kai']",,,,
,PMC,Chimeric severe acute respiratory syndrome coronavirus (SARS-CoV) S glycoprotein and influenza matrix 1 efficiently form virus-like particles (VLPs) that protect mice against challenge with SARS-CoV,http://dx.doi.org/10.1016/j.vaccine.2011.06.111,PMC3165014,,,"SARS-CoV was the cause of the global pandemic in 2003 that infected over 8000 people in 8 months. Vaccines against SARS are still not available. We developed a novel method to produce high levels of a recombinant SARS virus-like particles (VLPs) vaccine containing the SARS spike (S) protein and the influenza M1 protein using the baculovirus insect cell expression system. These chimeric SARS VLPs have a similar size and morphology to the wild type SARS-CoV. We tested the immunogenicity and protective efficacy of purified chimeric SARS VLPs and full length SARS S protein vaccines in a mouse lethal challenge model. The SARS VLP vaccine, containing 0.8 μg of SARS S protein, completely protected mice from death when administered intramuscular (IM) or intranasal (IN) routes in the absence of an adjuvant. Likewise, the SARS VLP vaccine, containing 4 μg of S protein without adjuvant, reduced lung virus titer to below detectable level, protected mice from weight loss, and elicited a high level of neutralizing antibodies against SARS-CoV. Sf9 cell-produced full length purified SARS S protein was also an effective vaccine against SARS-CoV but only when co-administered IM with aluminum hydroxide. SARS-CoV VLPs are highly immunogenic and induce neutralizing antibodies and provide protection against lethal challenge. Sf9 cell-based VLP vaccines are a potential tool to provide protection against novel pandemic agents.",,"['Liu, Ye V.', 'Massare, Michael J.', 'Barnard, Dale L.', 'Kort, Thomas', 'Nathan, Margret', 'Wang, Lei', 'Smith, Gale']",,,,
,PMC,Systemic responses during local viral infections: Type I IFNs sound the alarm,http://dx.doi.org/10.1016/j.coi.2011.06.003,PMC3163724,,,"Type I IFNs are well known for their role in controlling virus replication and spread. Type I IFNs produced by the infected tissue also signal beyond the boundaries of the infection to regulate different elements of the anti-viral immune response. Recent reports show that type I IFNs directly condition naive monocytes residing in the distal bone marrow and induce the expression of effector molecules in memory T cells, prior to their recruitment to the infected site. In addition, hematopoietic stem cells were shown to enter the cell cycle in response to systemic type I IFNs. These discoveries expand our understanding of the pleiotropic effects of type I IFNs during infection and highlight the involvement of the whole organism in the development of an effective response to a localized viral infection.",,"['López, Carolina B.', 'Hermesh, Tamar']",,,,
,PMC,Association of high viral load and abnormal liver function with high aflatoxin B(1)–albumin adduct levels in HIV-positive Ghanaians: preliminary observations,http://dx.doi.org/10.1080/19440049.2011.581698,PMC3381352,,,"We examined the association between certain clinical factors and aflatoxin B(1)–albumin adduct (AF-ALB) levels in HIV-positive people. Plasma samples collected from 314 (155 HIV-positive and 159 HIV-negative) people were tested for AF-ALB levels, viral load, CD4+ T-cell count, liver function profile, malaria parasitaemia, and hepatitis B and C virus infections. HIV-positive participants were divided into high and low groups based on their median AF-ALB of 0.93 pmol mg(−1) albumin and multivariable logistic and linear regression methods used to assess relationships between clinical conditions and AF-ALB levels. Multivariable logistic regression showed statistically significant increased odds of having higher HIV viral loads (OR=2.84; 95% CI=1.17–7.78) and higher direct bilirubin levels (OR=5.47; 95% CI=1.03–22.85) among HIV-positive participants in the high AF-ALB group. There were also higher levels of total bilirubin and lower levels of albumin in association with high AF-ALB. Thus, aflatoxin exposure may contribute to high viral loads and abnormal liver function in HIV-positive people and so promote disease progression.",,"['Jolly, P.E.', 'Shuaib, F.M.', 'Jiang, Y.', 'Preko, P.', 'Baidoo, J.', 'Stiles, J.K.', 'Wang, J.-S.', 'Phillips, T.D.', 'Williams, J.H.']",,,,
,PMC,Human Monoclonal Antibody Fragments Binding to Insulin-like Growth Factors 1 and 2 with Picomolar Affinity,http://dx.doi.org/10.1158/1535-7163.MCT-11-0281,PMC3170999,,,"The type 1 insulin-like growth factor receptor (IGF1R) and its ligands (IGF1 and IGF2) have been implicated in a variety of physiological processes and in diseases such as cancer. In addition to IGF1R, IGF2 also activates the insulin receptor (IR) isoform A and therefore antibodies against IGF2 can inhibit cell proliferation mediated by the signaling through both IGF1R and IR triggered by IGF2. We identified a new human monoclonal antibody (mAb), m708.2, which bound to IGF1 and IGF2 but not to insulin. m708.2 potently inhibited signal transduction mediated by the interaction of IGF1 or IGF2 with the IGF1R and IGF2 with the IR. It also inhibited the growth of the breast cancer cell line MCF-7. An affinity-matured derivative of m708.2, m708.5, bound to IGF1 with equilibrium dissociation constant, K(D) = 200 pM and to IGF2 with K(D) = 60 pM. m708.5 inhibited signal transduction mediated by IGF1 and IGF2 and cancer cell growth more potently than m708.2. These results suggest that m708.5 could have potential as a candidate therapeutic for cancers driven by the IGF1,2 interactions with IGF1R and IR.",,"['Zhao, Qi', 'Feng, Yang', 'Zhu, Zhongyu', 'Dimitrov, Dimiter S.']",,,,
,PMC,Use of a novel virus detection assay to identify coronavirus HKU1 in the lungs of a hematopoietic stem cell transplant recipient with fatal pneumonia,http://dx.doi.org/10.1111/j.1399-3062.2011.00657.x,PMC3416037,,,"A 38-year-old patient with systemic lupus erythematosus presented with pulmonary infiltrates and hypoxemia for several months following immunodepleting autologous hematopoietic stem cell transplantation. She was treated for influenza, which was isolated repeatedly from ororpharynx and bronchoalveolar lavage fluids, and later empirically for lupus pneumonitis, but expired 6 months after transplant. Autopsy findings failed to show influenza in the lungs or lupus pneumonitis. A novel generic PCR-based assay using degenerate primers identified human coronavirus HKU1 RNA in bronchoalveolar lavage fluid at autopsy. Coronavirus was confirmed by virus-specific PCRs of lung tissue at autopsy. Electron microscopy showed viral particles consistent with coronavirus HKU1 in lung tissue both at autopsy and from a previous biopsy. While human coronavirus HKU1 infection is not usually severe, in highly immunocompromised patients, it can be associated with fatal pneumonia.",,"['Uhlenhaut, Christine', 'Cohen, Jeffrey I.', 'Pavletic, Steven', 'Illei, Gabor', 'Gea-Banacloche, Juan Carlos', 'Abu-Asab, Mones', 'Krogmann, Tammy', 'Gubareva, Larisa', 'McClenahan, Shasta', 'Krause, Philip R.']",,,,
,PMC,Influenza Transmission in Households During the 1918 Pandemic,http://dx.doi.org/10.1093/aje/kwr122,PMC3695637,,,"Analysis of historical data has strongly shaped our understanding of the epidemiology of pandemic influenza and informs analysis of current and future epidemics. Here, the authors analyzed previously unpublished documents from a large household survey of the “Spanish” H1N1 influenza pandemic, conducted in 1918, for the first time quantifying influenza transmissibility at the person-to-person level during that most lethal of pandemics. The authors estimated a low probability of person-to-person transmission relative to comparable estimates from seasonal influenza and other directly transmitted infections but similar to recent estimates from the 2009 H1N1 pandemic. The authors estimated a very low probability of asymptomatic infection, a previously unknown parameter for this pandemic, consistent with an unusually virulent virus. The authors estimated a high frequency of prior immunity that they attributed to a largely unreported influenza epidemic in the spring of 1918 (or perhaps to cross-reactive immunity). Extrapolating from this finding, the authors hypothesize that prior immunity partially protected some populations from the worst of the fall pandemic and helps explain differences in attack rates between populations. Together, these analyses demonstrate that the 1918 influenza virus, though highly virulent, was only moderately transmissible and thus in a modern context would be considered controllable.",,"['Fraser, Christophe', 'Cummings, Derek A. T.', 'Klinkenberg, Don', 'Burke, Donald S.', 'Ferguson, Neil M.']",,,,
,PMC,Proteomic Characterization of Influenza H5N1 virus-like particles and their protective immunogenicity,http://dx.doi.org/10.1021/pr200086v,PMC3151535,,,"Recombinant virus-like particles (VLPs) have been shown to induce protective immunity. Despite of their potential significance as promising vaccine candidates, the protein composition of VLPs produced in insect cells has not been well characterized. Here we report a proteomic analysis of influenza VLPs containing hemagglutinin (HA) and matrix M1 proteins from a human isolate of avian influenza H5N1 virus (H5 VLPs) produced in insect cells using the recombinant baculovirus expression system. Comprehensive proteomic analysis of purified H5 VLPs identified viral proteins and 37 additional host-derived proteins, many of which are known to be present in other enveloped viruses. Proteins involved in different cellular structures and functions were found to be present in H5 VLPs including those from the cytoskeleton, translation, chaperone, and metabolism. Immunization with purified H5 VLPs induced protective immunity, which was comparable to the inactivated whole virus containing all viral components. Unpurified H5 VLPs containing excess amounts of non-influenza soluble proteins also conferred 100% protection against lethal challenge although lower immune responses were induced. These results provide important implications consistent with the idea that VLP production in insect cells may involve similar cellular machinery as other RNA enveloped viruses during synthesis, assembly, trafficking, and budding processes.",,"['Song, Jae-Min', 'Choi, Chi-Won', 'Kwon, Sang-Oh', 'Compans, Richard. W.', 'Kang, Sang-Moo', 'Kim, Seung Il']",,,,
,PMC,Methods of Measuring Compliance with Transmission-Based Isolation Precautions: Comparison of Paper-Based and Electronic Data Collection,http://dx.doi.org/10.1016/j.ajic.2011.01.020,PMC3193891,,,"BACKGROUND: Decreasing transmission of resistant organisms in hospitals is a key goal of infection prevention plans. Studies have shown that health care worker (HCW) compliance with isolation precautions is inadequate. Direct observation of HCW behavior for measuring adherence is considered the “gold standard” but is labor intensive, requiring the collection and analysis of a large volume of observations. METHODS: Two methods of data collection were evaluated to asses HCW compliance: a manual method using a paper form (PF) with subsequent data entry into a database, and an electronic method using a web-based form (WBF) with real-time data recording. Observations were conducted at four hospitals (2,065 beds) to assess availability of gloves, gowns and masks, isolation sign postings, and HCW isolation practices. RESULTS: A total of 13,878 isolation rooms were observed in 2009. The median number of rooms observed/day for PF and WBF were 61 and 60 and the mean observation times/room were 149sec and 60sec, respectively. The WBF provided a time savings of 89 sec/room. CONCLUSIONS: Simple electronic forms can significantly decrease resources needed to monitor HCW adherence to hospital policies. The WBF decreased observation time by 60%, allowing for an increase in frequency and expansion of surveillance activities.",,,,,,
,PMC,Multi-conformation 3D QSAR study of benzenesulfonyl-pyrazol-ester compounds and their analogs as cathepsin B inhibitors,http://dx.doi.org/10.1016/j.jmgm.2011.06.013,PMC3167229,,,"Cathepsin B has been found being responsible for many human diseases. Inhibitors of cathepsin B, a ubiquitous lysosomal cysteine protease, have been developed as a promising treatment for human diseases resulting from malfunction and over-expression of this enzyme. Through a high throughput screening assay, a set of compounds were found able to inhibit the enzymatic activity of cathepsin B. The binding structures of these active compounds were modeled through docking simulation. Three-dimensional (3D) quantitative structure-activity relationship (QSAR) models were constructed using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) based on the docked structures of the compounds. Strong correlations were obtained for both CoMFA and CoMSIA models with cross-validated correlation coefficients (q(2)) of 0.605 and 0.605 and the regression correlation coefficients (r(2)) of 0.999 and 0.997, respectively. The robustness of these models was further validated using leave-one-out (LOO) method and training-test set method. The activities of eight (8) randomly selected compounds were predicted using models built from training set of compounds with prediction errors of less than 1 unit for most compounds in CoMFA and CoMSIA models. Structural features for compounds with improved activity are suggested based on the analysis of the CoMFA and CoMSIA contour maps and the property map of the protein ligand binding site. These results may help to provide better understanding of the structure-activity relationship of cathepsin B inhibitors and to facilitate lead optimization and novel inhibitor design. The multi-conformation method to build 3D QSAR is very effective approach to obtain satisfactory models with high correlation with experimental results and high prediction power for unknown compounds.",,"['Zhou, Zhigang', 'Wang, Yanli', 'Bryant, Stephen H.']",,,,
,PMC,Designed protein mimics of the Ebola virus glycoprotein GP2 α-helical bundle: Stability and pH effects,http://dx.doi.org/10.1002/pro.688,PMC3190153,,,"Ebola virus (EboV) belongs to the Filoviridae family of viruses that causes severe and fatal hemhorragic fever. Infection by EboV involves fusion between the virus and host cell membranes mediated by the envelope glycoprotein GP2 of the virus. Similar to the envelope glycoproteins of other viruses, the central feature of the GP2 ectodomain postfusion structure is a six-helix bundle formed by the protein's N- and C-heptad repeat regions (NHR and CHR, respectively). Folding of this six-helix bundle provides the energetic driving force for membrane fusion; in other viruses, designed agents that disrupt formation of the six-helix bundle act as potent fusion inhibitors. To interrogate determinants of EboV GP2-mediated membrane fusion, we designed model proteins that consist of the NHR and CHR segments linked by short protein linkers. Circular dichroism and gel filtration studies indicate that these proteins adopt stable α-helical folds consistent with design. Thermal denaturation indicated that the GP2 six-helix bundle is highly stable at pH 5.3 (melting temperature, T(m), of 86.8 ± 2.0°C and van't Hoff enthalpy, ΔH(vH), of −28.2 ± 1.0 kcal/mol) and comparable in stability to other viral membrane fusion six-helix bundles. We found that the stability of our designed α-helical bundle proteins was dependent on buffering conditions with increasing stability at lower pH. Small pH differences (5.3–6.1) had dramatic effects (ΔT(m) = 37°C) suggesting a mechanism for conformational control that is dependent on environmental pH. These results suggest a role for low pH in stabilizing six-helix bundle formation during the process of GP2-mediated viral membrane fusion.",,"['Harrison, Joseph S', 'Higgins, Chelsea D', 'Chandran, Kartik', 'Lai, Jonathan R']",,,,
,PMC,Physical interventions to interrupt or reduce the spread of respiratory viruses,http://dx.doi.org/10.1002/14651858.CD006207.pub4,PMC6993921,,,"BACKGROUND: Viral epidemics or pandemics of acute respiratory infections like influenza or severe acute respiratory syndrome pose a global threat. Antiviral drugs and vaccinations may be insufficient to prevent their spread. OBJECTIVES: To review the effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. SEARCH METHODS: We searched The Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL 2010, Issue 3), which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to October 2010), OLDMEDLINE (1950 to 1965), EMBASE (1990 to October 2010), CINAHL (1982 to October 2010), LILACS (2008 to October 2010), Indian MEDLARS (2008 to October 2010) and IMSEAR (2008 to October 2010). SELECTION CRITERIA: In this update, two review authors independently applied the inclusion criteria to all identified and retrieved articles and extracted data. We scanned 3775 titles, excluded 3560 and retrieved full papers of 215 studies, to include 66 papers of 67 studies. We included physical interventions (screening at entry ports, isolation, quarantine, social distancing, barriers, personal protection, hand hygiene) to prevent respiratory virus transmission. We included randomised controlled trials (RCTs), cohorts, case‐controls, before‐after and time series studies. DATA COLLECTION AND ANALYSIS: We used a standardised form to assess trial eligibility. We assessed RCTs by randomisation method, allocation generation, concealment, blinding and follow up. We assessed non‐RCTs for potential confounders and classified them as low, medium and high risk of bias. MAIN RESULTS: We included 67 studies including randomised controlled trials and observational studies with a mixed risk of bias. A total number of participants is not included as the total would be made up of a heterogenous set of observations (participant people, observations on participants and countries (object of some studies)). The risk of bias for five RCTs and most cluster‐RCTs was high. Observational studies were of mixed quality. Only case‐control data were sufficiently homogeneous to allow meta‐analysis. The highest quality cluster‐RCTs suggest respiratory virus spread can be prevented by hygienic measures, such as handwashing, especially around younger children. Benefit from reduced transmission from children to household members is broadly supported also in other study designs where the potential for confounding is greater. Nine case‐control studies suggested implementing transmission barriers, isolation and hygienic measures are effective at containing respiratory virus epidemics. Surgical masks or N95 respirators were the most consistent and comprehensive supportive measures. N95 respirators were non‐inferior to simple surgical masks but more expensive, uncomfortable and irritating to skin. Adding virucidals or antiseptics to normal handwashing to decrease respiratory disease transmission remains uncertain. Global measures, such as screening at entry ports, led to a non‐significant marginal delay in spread. There was limited evidence that social distancing was effective, especially if related to the risk of exposure. AUTHORS' CONCLUSIONS: Simple and low‐cost interventions would be useful for reducing transmission of epidemic respiratory viruses. Routine long‐term implementation of some measures assessed might be difficult without the threat of an epidemic.",,"['Jefferson, Tom', 'Del Mar, Chris B', 'Dooley, Liz', 'Ferroni, Eliana', 'Al‐Ansary, Lubna A', 'Bawazeer, Ghada A', 'van Driel, Mieke L', 'Nair, Sreekumaran', 'Jones, Mark A', 'Thorning, Sarah', 'Conly, John M']",,,,
,PMC,Unravelling transmission trees of infectious diseases by combining genetic and epidemiological data,http://dx.doi.org/10.1098/rspb.2011.0913,PMC3234549,,,"Knowledge on the transmission tree of an epidemic can provide valuable insights into disease dynamics. The transmission tree can be reconstructed by analysing either detailed epidemiological data (e.g. contact tracing) or, if sufficient genetic diversity accumulates over the course of the epidemic, genetic data of the pathogen. We present a likelihood-based framework to integrate these two data types, estimating probabilities of infection by taking weighted averages over the set of possible transmission trees. We test the approach by applying it to temporal, geographical and genetic data on the 241 poultry farms infected in an epidemic of avian influenza A (H7N7) in The Netherlands in 2003. We show that the combined approach estimates the transmission tree with higher correctness and resolution than analyses based on genetic or epidemiological data alone. Furthermore, the estimated tree reveals the relative infectiousness of farms of different types and sizes.",,"['Ypma, R. J. F.', 'Bataille, A. M. A.', 'Stegeman, A.', 'Koch, G.', 'Wallinga, J.', 'van Ballegooijen, W. M.']",,,,
,PMC,Genome-wide screening using RNAi (RNA interference) to study host factors in viral replication and pathogenesis,http://dx.doi.org/10.1258/ebm.2010.010272,PMC3415036,,,"With the recent development of siRNA and shRNA expression libraries, RNAi technology has been extensively employed to identify genes involved in diverse cellular processes, such as signal transduction, cell cycle, cancer biology and host-pathogen interactions. In the field of viral infection, this approach has already identified hundreds of new genes not previously known to be important for various virus lifecycles. In this brief review, we focus on recent studies performed using genome-wide RNAi-based screens in mammalian cells for the identification of essential host factors for viral infection and pathogenesis.",,"['Houzet, Laurent', 'Jeang, Kuan-Teh']",,,,
,PMC,The use of mathematical models to inform influenza pandemic preparedness and response,http://dx.doi.org/10.1258/ebm.2010.010271,PMC3178755,,,"Influenza pandemics have occurred throughout history and were associated with substantial excess mortality and morbidity. Mathematical models of infectious diseases permit quantitative description of epidemic processes based on the underlying biological mechanisms. Mathematical models have been widely used in the past decade to aid pandemic planning by allowing detailed predictions of the speed of spread of an influenza pandemic and the likely effectiveness of alternative control strategies. During the initial waves of the 2009 influenza pandemic, mathematical models were used to track the spread of the virus, predict the time course of the pandemic and assess the likely impact of large-scale vaccination. While mathematical modeling has made substantial contributions to influenza pandemic preparedness, its use as a real-time tool for pandemic control is currently limited by the lack of essential surveillance information such as serologic data. Mathematical modeling provided a useful framework for analyzing and interpreting surveillance data during the 2009 influenza pandemic, for highlighting limitations in existing pandemic surveillance systems, and for guiding how these systems should be strengthened in order to cope with future epidemics of influenza or other emerging infectious diseases.",,"['Wu, Joseph T', 'Cowling, Benjamin J']",,,,
,PMC,Why do RNA viruses recombine?,http://dx.doi.org/10.1038/nrmicro2614,PMC3324781,,,"Recombination occurs in many RNA viruses and can be of major evolutionary significance. However, rates of recombination vary dramatically among RNA viruses, which can range from clonal to highly recombinogenic. Here, we review the factors that might explain this variation in recombination frequency and show that there is little evidence that recombination is favoured by natural selection to create advantageous genotypes or purge deleterious mutations, as predicted if recombination functions as a form of sexual reproduction. Rather, recombination rates seemingly reflect larger-scale patterns of viral genome organization, such that recombination may be a mechanistic by-product of the evolutionary pressures acting on other aspects of virus biology.",,"['Simon-Loriere, Etienne', 'Holmes, Edward C.']",,,,
,PMC,Development of NGR peptide-based agents for tumor imaging,,PMC3477716,,,"Molecular imaging allows direct visualization of targets and characterization of cellular pathways, as long as a high signal/background ratio can be achieved, which requires a sufficient amount of probes to accumulate in the imaging region. The Asn-Gly-Arg (NGR) tripeptide selected by phage display can specifically target tumor vasculature. Recognizing the aminopeptidase N (APN or CD13) receptor on the membrane of tumor cells, the peptide can be further internalized into cytoplasma by the endosomal pathway. Hence NGR can serve as an ideal candidate for tumor imaging, once it is conjugated with fluorescent or radiolabeled imaging probes. Herein, we highlight some recent developments of NGR peptide based imaging of tumors. Although still in the preliminary stage, some NGR probes have shown potential as promising agents in future clinical applications.",,"['Wang, Rongsheng E.', 'Niu, Youhong', 'Wu, Haifan', 'Amin, Mohamad Nassir', 'Cai, Jianfeng']",,,,
,PMC,Excessive Neutrophils and Neutrophil Extracellular Traps Contribute to Acute Lung Injury of Influenza Pneumonitis,http://dx.doi.org/10.1016/j.ajpath.2011.03.013,PMC3123873,,,"Complications of acute respiratory distress syndrome (ARDS) are common among critically ill patients infected with highly pathogenic influenza viruses. Macrophages and neutrophils constitute the majority of cells recruited into infected lungs, and are associated with immunopathology in influenza pneumonia. We examined pathological manifestations in models of macrophage- or neutrophil-depleted mice challenged with sublethal doses of influenza A virus H1N1 strain PR8. Infected mice depleted of macrophages displayed excessive neutrophilic infiltration, alveolar damage, and increased viral load, later progressing into ARDS-like pathological signs with diffuse alveolar damage, pulmonary edema, hemorrhage, and hypoxemia. In contrast, neutrophil-depleted animals showed mild pathology in lungs. The brochoalveolar lavage fluid of infected macrophage-depleted mice exhibited elevated protein content, T1-α, thrombomodulin, matrix metalloproteinase-9, and myeloperoxidase activities indicating augmented alveolar-capillary damage, compared to neutrophil-depleted animals. We provide evidence for the formation of neutrophil extracellular traps (NETs), entangled with alveoli in areas of tissue injury, suggesting their potential link with lung damage. When co-incubated with infected alveolar epithelial cells in vitro, neutrophils from infected lungs strongly induced NETs generation, and augmented endothelial damage. NETs induction was abrogated by anti-myeloperoxidase antibody and an inhibitor of superoxide dismutase, thus implying that NETs generation is induced by redox enzymes in influenza pneumonia. These findings support the pathogenic effects of excessive neutrophils in acute lung injury of influenza pneumonia by instigating alveolar-capillary damage.",,"['Narasaraju, Teluguakula', 'Yang, Edwin', 'Samy, Ramar Perumal', 'Ng, Huey Hian', 'Poh, Wee Peng', 'Liew, Audrey-Ann', 'Phoon, Meng Chee', 'van Rooijen, Nico', 'Chow, Vincent T.']",,,,
,PMC,Pathogenesis of Influenza A/H5N1 Virus Infection in Ferrets Differs between Intranasal and Intratracheal Routes of Inoculation,http://dx.doi.org/10.1016/j.ajpath.2011.03.026,PMC3123863,,,"Most patients infected with highly pathogenic avian influenza A/H5N1 virus develop severe pneumonia resulting in acute respiratory distress syndrome, with extrarespiratory disease as an uncommon complication. Intranasal inoculation of ferrets with influenza A/H5N1 virus causes lesions in both the respiratory tract and extrarespiratory organs (primarily brain). However, the route of spread to extrarespiratory organs and the relative contribution of extrarespiratory disease to pathogenicity are largely unknown. In the present study, we characterized lesions in the respiratory tract and central nervous system (CNS) of ferrets (n = 8) inoculated intranasally with influenza virus A/Indonesia/5/2005 (H5N1). By 7 days after inoculation, only 3 of 8 ferrets had a mild or moderate bronchointerstitial pneumonia. In contrast, all 8 ferrets had moderate or severe CNS lesions, characterized by meningoencephalitis, choroiditis, and ependymitis, and centered on tissues adjoining the cerebrospinal fluid. These findings indicate that influenza A/H5N1 virus spread directly from nasal cavity to brain, and that CNS lesions contributed more than pulmonary lesions to the pathogenicity of influenza A/H5N1 virus infection in ferrets. In comparison, intratracheal inoculation of ferrets with the same virus reproducibly caused severe bronchointerstitial pneumonia. The method of virus inoculation requires careful consideration in the design of ferret experiments as a model for influenza A/H5N1 in humans.",,"['Bodewes, Rogier', 'Kreijtz, Joost H.C.M.', 'van Amerongen, Geert', 'Fouchier, Ron A.M.', 'Osterhaus, Albert D.M.E.', 'Rimmelzwaan, Guus F.', 'Kuiken, Thijs']",,,,
,PMC,"Etiology of Suspected Pneumonia in Adults Admitted to a High-Dependency Unit in Blantyre, Malawi",http://dx.doi.org/10.4269/ajtmh.2011.10-0640,PMC3122352,,,"The microbiologic etiology of severe pneumonia in hospitalized patients is rarely known in sub-Saharan Africa. Through a comprehensive diagnostic work-up, we aimed to identify the causative agent in severely ill patients with a clinical picture of pneumonia admitted to a high-dependency unit. A final diagnosis was made and categorized as confirmed or probable by using predefined criteria. Fifty-one patients were recruited (45% females), with a mean age of 35 years (range = 17–88 years), of whom 11(22%) died. Forty-eight (94%) of the patients were seropositive for human immunodeficiency virus; 14 (29%) of these patients were receiving antiretroviral treatment. Final diagnoses were bacterial pneumonia (29%), Pneumocystis jirovecii pneumonia (27%), pulmonary tuberculosis (22%), and pulmonary Kaposi's sarcoma (16%); 39 (77%) of these cases were confirmed cases. Fifteen (29%) patients had multiple isolates. At least 3 of 11 viral-positive polymerase chain reaction (PCR) results of bronchoalveolar lavage fluid were attributed clinical relevance. No atypical bacterial organisms were found.",,"['Hartung, Thomas K.', 'Chimbayo, Daniel', 'van Oosterhout, Joep J. G.', 'Chikaonda, Tarsizio', 'van Doornum, Gerard J. J.', 'Claas, Eric C. J.', 'Melchers, Willem J. G.', 'Molyneux, Malcolm E.', 'Zijlstra, Ed E.']",,,,
,PMC,Detection of Known and Novel Adenoviruses in Cattle Wastes via Broad-Spectrum Primers,http://dx.doi.org/10.1128/AEM.00625-11,PMC3147386,,,"The critical assessment of bovine adenoviruses (BAdV) as indicators of environmental fecal contamination requires improved knowledge of their prevalence, shedding dynamics, and genetic diversity. We examined DNA extracted from bovine and other animal waste samples collected in Wisconsin for atadenoviruses and mastadenoviruses using novel, broad-spectrum PCR primer sets. BAdV were detected in 13% of cattle fecal samples, 90% of cattle urine samples, and 100% of cattle manure samples; 44 percent of BAdV-positive samples contained both Atadenovirus and Mastadenovirus DNA. Additionally, BAdV were detected in soil, runoff water from a cattle feedlot, and residential well water. Overall, we detected 8 of 11 prototype BAdV, plus bovine, rabbit, and porcine mastadenoviruses that diverged significantly from previously reported genotypes. The prevalence of BAdV shedding by cattle supports targeting AdV broadly as indicators of the presence of fecal contamination in aqueous environments. Conversely, several factors complicate the use of AdV for fecal source attribution. Animal AdV infecting a given livestock host were not monophyletic, recombination among livestock mastadenoviruses was detected, and the genetic diversity of animal AdV is still underreported. These caveats highlight the need for continuing genetic surveillance for animal AdV and for supporting data when BAdV detection is invoked for fecal source attribution in environmental samples. To our knowledge, this is the first study to report natural BAdV excretion in urine, BAdV detection in groundwater, and recombination in AdV of livestock origin.",,"['Sibley, Samuel D.', 'Goldberg, Tony L.', 'Pedersen, Joel A.']",,,,
,PMC,Future perfect? Improving preparedness through the experiences of the influenza A (H1N1) 2009 pandemic,http://dx.doi.org/10.2471/BLT.11.091389,PMC3127282,,,,,"Penn, Charles R",,,,
,PMC,The classical definition of a pandemic is not elusive,http://dx.doi.org/10.2471/BLT.11.088815,PMC3127276,,,,,"Kelly, Heath",,,,
,PMC,Elder abuse: What are we missing?,,PMC3135443,,,,,"Vetere, Phyllis Marie",,,,
,PMC,"Interaction of Bordetella bronchiseptica, Pasteurella multocida, and fumonisin B1 in the porcine respiratory tract as studied by computed tomography",,PMC3122966,,,"The interaction of Bordetella bronchiseptica, toxigenic Pasteurella multocida serotype D, and the mycotoxin fumonisin B(1) (FB(1)) was studied. On day 0 of the experiment, 28 artificially reared 3-day-old piglets were divided into 4 groups (n = 7 each): a control group (A), a group fed FB(1) toxin (B), a group infected with the 2 pathogens (C), and a group infected with the 2 pathogens and fed FB(1) toxin (D). The B. bronchiseptica infection [with 10(6) colony-forming units (CFU)/mL] was performed on day 4 and the P. multocida infection (with 10(8) CFU/mL) on day 16. From day 16 a Fusarium verticillioides fungal culture (dietary FB(1) toxin content 10 mg/kg) was mixed into the feed of groups B and D. In groups C and D, clinical signs including mild serous nasal discharge, sneezing, panting, and hoarseness appeared from day 4, and then from day 16 some piglets had coughing and dyspnea as well. Computed tomography (CT) performed on day 16 demonstrated lung lesions attributable to colonization by B. bronchiseptica in the infected groups. By day 25 the number of piglets exhibiting lesions had increased, and the lesions appeared as well-circumscribed, focal changes characterized by a strong density increase in the affected areas of the lungs. The gross pathological findings confirmed the results obtained by CT. These results indicate that, when combined with dual infection by B. bronchiseptica and P. multocida, dietary exposure of pigs to FB(1) toxin raises the risk of pneumonia and increases the extent and severity of the pathological changes.",,"['Pósa, Roland', 'Donkó, Tamás', 'Bogner, Péter', 'Kovács, Melinda', 'Repa, Imre', 'Magyar, Tibor']",,,,
,PMC,Bovine coronavirus (BCV) infections in transported commingled beef cattle and sole-source ranch calves,,PMC3122965,,,"This study investigated bovine coronavirus (BCV) in both beef calves direct from the ranch and commingled, mixed-source calves obtained from an auction market. The level of BCV-neutralizing antibodies found in the calves varied among ranches in 2 different studies in a retained-ownership program (ROP), from the ranch to the feedlot. Calves with low levels of BCV-neutralizing antibodies (16 or less) were more likely to be treated for bovine respiratory disease (BRD) than those with higher titers. In 3 studies of commingled, mixed-source calves, BCV was recovered from calves at entry to the feedlot and the infections were cleared by day 8. The BCV was identified in lung samples [bronchoalveolar lavage (BAL) collection] as well as in nasal swabs. Calves with low levels of BCV-neutralizing antibodies at entry were most likely to be shedding BCV. Bovine coronavirus was isolated from both healthy and sick calves, but not from sick calves after 4 d arrival at the feedlot. Bovine coronavirus (BCV) should be considered along with other bovine respiratory viruses in the diagnosis of etiologies in bovine respiratory disease, especially for animals that become sick shortly after arrival. If approved vaccines are developed, it would be best to carry out vaccination programs before calves are weaned, giving them sufficient time to gain active immunity before commingling with other cattle.",,"['Fulton, Robert W.', 'Step, Douglas L.', 'Wahrmund, Jackie', 'Burge, Lurinda J.', 'Payton, Mark E.', 'Cook, Billy J.', 'Burken, Dirk', 'Richards, Chris J.', 'Confer, Anthony W.']",,,,
,PMC,Presumptive bovine neonatal pancytopenia in a Holstein calf in Québec,,PMC3119246,,,"An 18-day-old heifer was presented with fever, depression, tachycardia, tachypnea, and prolonged bleeding time. Blood tests revealed severe anemia, thrombocytopenia, and leucopenia. The animal was negative by PCR for bovine virus diarrhea virus antigen. The findings supported a diagnosis of bovine neonatal pancytopenia. Treatments included fresh whole blood transfusion and antibiotics. The animal recovered fully.",,"['Gosselin, Véronique Bernier', 'Fecteau, Gilles', 'Nichols, Sylvain']",,,,
,PMC,Oral and Nasal DNA Vaccines Delivered by Attenuated Salmonella enterica Serovar Typhimurium Induce a Protective Immune Response against Infectious Bronchitis in Chickens,http://dx.doi.org/10.1128/CVI.00034-11,PMC3147333,,,"Several studies have reported that intramuscular injection of DNA vaccines against infectious bronchitis virus (IBV) induces protective immune responses. In the present study, we developed oral and nasal DNA vaccines that carried the S1 gene and N gene of IBV delivered by attenuated Salmonella enterica serovar Typhimurium strains SL/pV-S1 and SL/pV-N, respectively. The safety and stability of recombinant Salmonella vaccine were evaluated. Following oral and nasal administration to chickens, the serum and mucosal samples were collected and antibodies against IBV were measured. Chickens were then challenged with IBV strain M41 by the nasal-ocular route 3 weeks after boosting. The results showed that oral and nasal immunization with coadministered SL/pV-S1 and SL/pV-N elicited significant IBV-specific humoral and mucosal immune responses and conferred protective efficacy against IBV challenge higher than that in chickens immunized only with SL/pV-S1. The current study shows that novel DNA vaccines delivered by attenuated S. Typhimurium may be promising candidates for the prevention of infectious bronchitis (IB).These vaccines are efficacious, easily produced economically, and able to be delivered orally and nasally rather than injected. Coadministration of SL/pV-S1 and SL/pV-N may represent an effective mucosal vaccination regimen.",,"['Jiao, Hongmei', 'Pan, Zhiming', 'Yin, Yuelan', 'Geng, Shizhong', 'Sun, Lin', 'Jiao, Xinan']",,,,
,PMC,Evaluation of Oral Immunization with Recombinant Avian Influenza Virus HA1 Displayed on the Lactococcus lactis Surface and Combined with the Mucosal Adjuvant Cholera Toxin Subunit B,http://dx.doi.org/10.1128/CVI.00050-11,PMC3147322,,,"The development of safe and efficient avian influenza vaccines for human and animal uses is essential for preventing virulent outbreaks and pandemics worldwide. In this study, we constructed a recombinant (pgsA-HA1 gene fusion) Lactococcus lactis strain that expresses and displays the avian influenza virus HA1 antigens on its surface. The vectors were administered by oral delivery with or without the addition of cholera toxin subunit B (CTB). The resulting immune responses were analyzed, and the mice were eventually challenged with lethal doses of H5N1 viruses. Significant titers of hemagglutinin (HA)-specific serum IgG and fecal IgA were detected in the group that also received CTB. Cellular immunities were also shown in both cell proliferation and gamma interferon (IFN-γ) enzyme-linked immunospot (ELISpot) assays. Most importantly, the mice that received the L. lactis pgsA-HA1 strain combined with CTB were completely protected from lethal challenge of the H5N1 virus. These findings support the further development of L. lactis-based avian influenza virus vaccines for human and animal uses.",,"['Lei, Han', 'Sheng, Zhina', 'Ding, Qian', 'Chen, Jian', 'Wei, Xiaohui', 'Lam, Dominic Man-Kit', 'Xu, Yuhong']",,,,
,PMC,Viral infection: Moving through complex and dynamic cell-membrane structures,http://dx.doi.org/10.4161/cib.4.4.16716,PMC3181506,,,"Viruses have developed different survival strategies in host cells by crossing cell-membrane compartments, during different steps of their viral life cycle. In fact, the non-regenerative viral membrane of enveloped viruses needs to encounter the dynamic cell-host membrane, during early steps of the infection process, in which both membranes fuse, either at cell-surface or in an endocytic compartment, to promote viral entry and infection. Once inside the cell, many viruses accomplish their replication process through exploiting or modulating membrane traffic, and generating specialized compartments to assure viral replication, viral budding and spreading, which also serve to evade the immune responses against the pathogen. In this review, we have attempted to present some data that highlight the importance of membrane dynamics during viral entry and replicative processes, in order to understand how viruses use and move through different complex and dynamic cell-membrane structures and how they use them to persist.",,"['Barroso-González, Jonathan', 'García-Expósito, Laura', 'Puigdomènech, Isabel', 'de Armas-Rillo, Laura', 'Machado, José-David', 'Blanco, Julià', 'Valenzuela-Fernández, Agustín']",,,,
,PMC,Experimental Models and Emerging Hypotheses for Acute Lung Injury,http://dx.doi.org/10.1016/j.ccc.2011.05.013,PMC3159414,,,"Acute Lung Injury (ALI) is a complex illness involving the activation of multiple pathways leading to lung injury, resolution and repair. Since the first description of ALI, a great deal of effort has been devoted to exploring the roles of individual pathways in humans and animal models. These have led to a much greater understanding of the complexity of ALI and the links between ALI and systemic multiorgan failure. Despite progress in many areas, we still do not have an integrated understanding of the initiating factors, the key steps in the progression of ALI, and the central processes involved in repair. Although animal models have suggested a range of new hypotheses for study, the major need is for a better understanding of how pathways interact to explain the complexity of the human ALI syndrome and how complementary treatments can be used simultaneously or sequentially to modify the onset, severity and outcome of ALI in humans.",,"['Martin, Thomas R.', 'Matute-Bello, Gustavo']",,,,
,PMC,Viral envelope protein folding and membrane hemifusion are enhanced by the conserved loop region of HIV-1 gp41,http://dx.doi.org/10.1096/fj.10-175752,PMC3114521,,,"Fusion of human immunodeficiency virus (HIV-1) with target cells is mediated by the gp41 transmembrane envelope protein. The loop region within gp41 contains 2 crucial cysteines that play an unknown role in HIV-cell fusion. On the basis of cell-cell fusion assay, using human T-cell lines [Jurkat E6-1 and Jurkat HXBc2(4)], and virus-cell fusion assay, using fully infectious HIV-1 HXBc2 virus and TZM-bl human cell line, we provide evidence that the oxidation state of the disulfide bond within a loop domain peptide determines its activity. The oxidized (closed) form inhibits fusion, while the reduced (opened) form enhances hemifusion. These opposite activities reach 60% difference in viral fusion. Both forms of the loop domain interact with gp41: the opened form enhances gp41 folding into a bundle, whereas the closed form inhibits this folding. Therefore, the transformation of the cysteines from a reduced to an oxidized state enables the loop to convert from opened to closed conformations, which assists gp41 to fold and induces hemifusion. The significant conservation of the loop region within many envelope proteins suggests a general mechanism, which is exploited by viruses to enhance entry into their host cells.—Ashkenazi, A., Viard, M., Wexler-Cohen, Y., Blumenthal, R., Shai, Y. Viral envelope protein folding and membrane hemifusion are enhanced by the conserved loop region of HIV-1 gp41.",,"['Ashkenazi, Avraham', 'Viard, Mathias', 'Wexler-Cohen, Yael', 'Blumenthal, Robert', 'Shai, Yechiel']",,,,
,PMC,Prioritizing candidate disease genes by network-based boosting of genome-wide association data,http://dx.doi.org/10.1101/gr.118992.110,PMC3129253,,,"Network “guilt by association” (GBA) is a proven approach for identifying novel disease genes based on the observation that similar mutational phenotypes arise from functionally related genes. In principle, this approach could account even for nonadditive genetic interactions, which underlie the synergistic combinations of mutations often linked to complex diseases. Here, we analyze a large-scale, human gene functional interaction network (dubbed HumanNet). We show that candidate disease genes can be effectively identified by GBA in cross-validated tests using label propagation algorithms related to Google's PageRank. However, GBA has been shown to work poorly in genome-wide association studies (GWAS), where many genes are somewhat implicated, but few are known with very high certainty. Here, we resolve this by explicitly modeling the uncertainty of the associations and incorporating the uncertainty for the seed set into the GBA framework. We observe a significant boost in the power to detect validated candidate genes for Crohn's disease and type 2 diabetes by comparing our predictions to results from follow-up meta-analyses, with incorporation of the network serving to highlight the JAK–STAT pathway and associated adaptors GRB2/SHC1 in Crohn's disease and BACH2 in type 2 diabetes. Consideration of the network during GWAS thus conveys some of the benefits of enrolling more participants in the GWAS study. More generally, we demonstrate that a functional network of human genes provides a valuable statistical framework for prioritizing candidate disease genes, both for candidate gene-based and GWAS-based studies.",,"['Lee, Insuk', 'Blom, U. Martin', 'Wang, Peggy I.', 'Shim, Jung Eun', 'Marcotte, Edward M.']",,,,
,PMC,"Rhinoviruses, Allergic Inflammation, and Asthma",http://dx.doi.org/10.1111/j.1600-065X.2011.01031.x,PMC3119863,,,"Viral infections affect wheezing and asthma in children and adults of all ages. In infancy, wheezing illnesses are usually viral in origin, and children with more severe wheezing episodes are more likely to develop recurrent episodes of asthma and to develop asthma later in childhood. Children who develop allergen-specific immunoglobulin E (allergic sensitization), and those who wheeze with rhinoviruses (HRV) are at especially high risk for asthma. In older children and adults, HRV infections generally cause relatively mild respiratory illnesses and yet contribute to acute and potentially severe exacerbations in patients with asthma. These findings underline the importance of understanding the synergistic nature of allergic sensitization and infections with HRV in infants relative to the onset of asthma and in children and adults with respect to exacerbations of asthma. This review discusses clinical and experimental evidence of virus/allergen interactions and evaluates theories which relate immunologic responses to respiratory viruses and allergens to the pathogenesis and disease activity of asthma. Greater understanding of the relationship between viral respiratory infections, allergic inflammation, and asthma is likely to suggest new strategies for the prevention and treatment of asthma.",,"['Gavala, Monica', 'Bertics, Paul J.', 'Gern, James E.']",,,,
,PMC,The role of myeloid receptors on murine plasmacytoid dendritic cells in induction of type I interferon,http://dx.doi.org/10.1016/j.intimp.2011.01.013,PMC3121950,21281752,CC BY,"This study tested the hypothesis that a set of predominantly myeloid restricted receptors (F4/80, CD36, Dectin-1, CD200 receptor and mannan binding lectins) and the broadly expressed CD200 played a role in a key function of plasmacytoid DC (pDC), virally induced type I interferon (IFN) production. The Dectin-1 ligands zymosan, glucan phosphate and the anti-Dectin-1 monoclonal antibody (mAb) 2A11 had no effect on influenza virus induced IFNα/β production by murine splenic pDC. However, mannan, a broad blocking reagent against mannose specific receptors, inhibited IFNα/β production by pDC in response to inactivated influenza virus. Moreover, viral glycoproteins (influenza virus haemagglutinin and HIV-1 gp120) stimulated IFNα/β production by splenocytes in a mannan-inhibitable manner, implicating the function of a lectin in glycoprotein induced IFN production. Lastly, the effect of CD200 on IFN induction was investigated. CD200 knock-out macrophages produced more IFNα than wild-type macrophages in response to polyI:C, a MyD88-independent stimulus, consistent with CD200's known inhibitory effect on myeloid cells. In contrast, blocking CD200 with an anti-CD200 mAb resulted in reduced IFNα production by pDC-containing splenocytes in response to CpG and influenza virus (MyD88-dependent stimuli). This suggests there could be a differential effect of CD200 on MyD88 dependent and independent IFN induction pathways in pDC and macrophages. This study supports the hypothesis that a mannan-inhibitable lectin and CD200 are involved in virally induced type I IFN induction.",2011 Jul,"['Seeds, Rosalind E.', 'Mukhopadhyay, Subhankar', 'Jones, Ian M.', 'Gordon, Siamon', 'Miller, Joanna L.']",Int Immunopharmacol,,,
,PMC,Comparison of Two Multiplex Methods for Detection of Respiratory Viruses: FilmArray RP and xTAG RVP,http://dx.doi.org/10.1128/JCM.02582-10,PMC3147849,,,"We compared the FilmArray RP (Idaho Technology, Inc., Salt Lake City, UT) and the xTAG RVP (Luminex Corporation, Toronto, Canada) multiplex respiratory virus PCR methods for the detection of respiratory viruses in a set of 200 patient specimens frozen at −70°C after standard viral culture and antigen detection methods were done. Both systems detected between 40 to 50% more viruses than traditional methods, primarily rhinoviruses and human metapneumovirus. The FilmArray RP detected significantly more total viruses either alone or as part of mixed infections than the xTAG RVP, as well as an additional 21.6% more respiratory syncytial viruses. The xTAG RVP requires 5 to 6 h with 2.5 to 3 h of hands-on time, while the FilmArray RP takes about an hour with 3 to 5 min of hands-on time, making it much easier to perform.",,"['Rand, Kenneth H.', 'Rampersaud, Howard', 'Houck, Herbert J.']",,,,
,PMC,Histologic and Molecular Correlation in Shelter Cats with Acute Upper Respiratory Infection,http://dx.doi.org/10.1128/JCM.00187-11,PMC3147833,,,"This is a descriptive study designed to correlate diagnostic real-time PCR results with histopathologic lesions in cats with clinical signs of upper respiratory infection (URI). The study occurred over a 9-month period in a single open-intake animal shelter. Cats that were selected for euthanasia by the shelter staff and additionally had URI were included in the study, for a total of 22 study cats. Combined conjunctival and oropharyngeal swab specimens were tested by quantitative real-time PCR (qPCR) for feline herpesvirus type 1 (FHV-1), feline calicivirus (FCV), Mycoplasma felis, Chlamydophila felis, and Bordetella bronchiseptica. Necropsy was performed on all cats, and a complete set of respiratory tract tissues was examined by histopathology. Among 22 cats, 20 were qPCR positive for FHV-1, 7 for M. felis, 5 for FCV, 1 for C. felis, and 0 for B. bronchiseptica. Nine cats were positive for two or more pathogens. Histopathologic lesions were present in all cats, with consistent lesions in the nasal cavity, including acute necroulcerative rhinitis in 16 cats. Histologic or antigenic detection of FHV-1 was seen in 18 of 20 cats positive for FHV-1 by qPCR. No lesions that could be specifically attributed to FCV, M. felis, or C. felis were seen, although interpretation in this cohort could be confounded by coinfection with FHV-1. A significant agreement was found between the amount of FHV-1 DNA determined by qPCR and the presence of specific histopathologic lesions for FHV-1 but not for the other respiratory pathogens.",,"['Burns, Rachel E.', 'Wagner, Denae C.', 'Leutenegger, Christian M.', 'Pesavento, Patricia A.']",,,,
,PMC,Design and Performance of the CDC Real-Time Reverse Transcriptase PCR Swine Flu Panel for Detection of 2009 A (H1N1) Pandemic Influenza Virus,http://dx.doi.org/10.1128/JCM.02636-10,PMC3147828,,,"Swine influenza viruses (SIV) have been shown to sporadically infect humans and are infrequently identified by the Influenza Division of the Centers for Disease Control and Prevention (CDC) after being received as unsubtypeable influenza A virus samples. Real-time reverse transcriptase PCR (rRT-PCR) procedures for detection and characterization of North American lineage (N. Am) SIV were developed and implemented at CDC for rapid identification of specimens from cases of suspected infections with SIV. These procedures were utilized in April 2009 for detection of human cases of 2009 A (H1N1) pandemic (pdm) influenza virus infection. Based on genetic sequence data derived from the first two viruses investigated, the previously developed rRT-PCR procedures were optimized to create the CDC rRT-PCR Swine Flu Panel for detection of the 2009 A (H1N1) pdm influenza virus. The analytical sensitivity of the CDC rRT-PCR Swine Flu Panel was shown to be 5 copies of RNA per reaction and 10(−1.3∼−0.7) 50% infectious doses (ID(50)) per reaction for cultured viruses. Cross-reactivity was not observed when testing human clinical specimens or cultured viruses that were positive for human seasonal A (H1N1, H3N2) and B influenza viruses. The CDC rRT-PCR Swine Flu Panel was distributed to public health laboratories in the United States and internationally from April 2009 until June 2010. The CDC rRT-PCR Swine Flu Panel served as an effective tool for timely and specific detection of 2009 A (H1N1) pdm influenza viruses and facilitated subsequent public health response implementation.",,"['Shu, Bo', 'Wu, Kai-Hui', 'Emery, Shannon', 'Villanueva, Julie', 'Johnson, Roy', 'Guthrie, Erica', 'Berman, LaShondra', 'Warnes, Christine', 'Barnes, Nathelia', 'Klimov, Alexander', 'Lindstrom, Stephen']",,,,
,PMC,Frequent Detection of Respiratory Viruses without Symptoms: Toward Defining Clinically Relevant Cutoff Values,http://dx.doi.org/10.1128/JCM.02094-10,PMC3147826,,,"Highly sensitive techniques, such as PCR, have greatly improved the detection of respiratory viruses. However, the sensitivity of PCR tests also complicates clinical interpretation, as the presence of small amounts of viral targets may not necessarily have clinical relevance. We performed a prospective case-control study in asymptomatic and symptomatic young children. PCR detection of 14 respiratory viruses was performed in nasal washes, and results were quantified in copies per milliliter. A total of 141 cases and 157 controls were included. In 72% of the cases and 28% of the controls, at least one virus was identified. When stratified for age, at least one virus was identified in 47% of the controls younger than 1 year old. Rhinovirus (RV) was frequently detected in both symptomatic and asymptomatic individuals. Receiver operating characteristic analysis for quantitative rhinovirus detection showed that cutoff values for clinical relevance are feasible for RV. In contrast to rhinovirus, respiratory syncytial virus (RSV) was rarely detected in controls, suggesting that a positive RSV test result is almost always of clinical relevance, independent of viral quantity. In conclusion, our study shows that asymptomatic carriage of a respiratory virus occurs frequently in young children. However, significant differences in the amount of virus present were observed between cases and controls. This suggests that defining cutoff levels should be feasible and represents the next necessary step for diagnosing viral respiratory infections using molecular tests.",,"['Jansen, Rogier R.', 'Wieringa, Joanne', 'Koekkoek, Sylvie M.', 'Visser, Caroline E.', 'Pajkrt, Dasja', 'Molenkamp, Richard', 'de Jong, Menno D.', 'Schinkel, Janke']",,,,
,PMC,Structure and Genetic Analysis of the Arterivirus Nonstructural Protein 7α,http://dx.doi.org/10.1128/JVI.00255-11,PMC3126611,,,"Arterivirus replicase polyproteins are cleaved into at least 13 mature nonstructural proteins (nsps), and in particular the nsp5-to-nsp8 region is subject to a complex processing cascade. The function of the largest subunit from this region, nsp7, which is further cleaved into nsp7α and nsp7β, is unknown. Using nuclear magnetic resonance (NMR) spectroscopy, we determined the solution structure of nsp7α of equine arteritis virus, revealing an interesting unique fold for this protein but thereby providing little clue to its possible functions. Nevertheless, structure-based reverse genetics studies established the importance of nsp7/nsp7α for viral RNA synthesis, thus providing a basis for future studies.",,"['Manolaridis, Ioannis', 'Gaudin, Cyril', 'Posthuma, Clara C.', 'Zevenhoven-Dobbe, Jessika C.', 'Imbert, Isabelle', 'Canard, Bruno', 'Kelly, Geoff', 'Tucker, Paul A.', 'Conte, Maria R.', 'Snijder, Eric J.']",,,,
,PMC,NS4B Self-Interaction through Conserved C-Terminal Elements Is Required for the Establishment of Functional Hepatitis C Virus Replication Complexes,http://dx.doi.org/10.1128/JVI.00502-11,PMC3126587,,,"Hepatitis C virus (HCV) is an important human pathogen, persistently infecting more than 170 million individuals worldwide. Studies of the HCV life cycle have become possible with the development of cell culture systems supporting the replication of viral RNA and the production of infectious virus. However, the exact functions of individual proteins, especially of nonstructural protein 4B (NS4B), remain poorly understood. NS4B triggers the formation of specific, vesicular membrane rearrangements, referred to as membranous webs, which have been reported to represent sites of HCV RNA replication. However, the mechanism of vesicle induction is not known. In this study, a panel of 15 mutants carrying substitutions in the highly conserved NS4B C-terminal domain was generated. Five mutations had only a minor effect on replication, but two of them enhanced assembly and release of infectious virus. Ten mutants were replication defective and used for selection of pseudoreversions. Most of the pseudoreversions also localized to the highly conserved NS4B C-terminal domain and were found to restore replication competence upon insertion into the corresponding primary mutant. Importantly, pseudoreversions restoring replication competence also restored heterotypic NS4B self-interaction, which was disrupted by the primary mutation. Finally, electron microscopy analyses of membrane alterations induced by NS4B mutants revealed striking morphological abnormalities, which were restored to wild-type morphology by the corresponding pseudoreversion. These findings demonstrate the important role of the C-terminal domain in NS4B self-interaction and the formation of functional HCV replication complexes.",,"['Paul, David', 'Romero-Brey, Inés', 'Gouttenoire, Jérôme', 'Stoitsova, Savina', 'Krijnse-Locker, Jacomine', 'Moradpour, Darius', 'Bartenschlager, Ralf']",,,,
,PMC,Inhibition of Human BK Polyomavirus Replication by Small Noncoding RNAs,http://dx.doi.org/10.1128/JVI.00547-11,PMC3126582,,,"Small noncoding RNAs regulate a variety of cellular processes, including genomic imprinting, chromatin remodeling, replication, transcription, and translation. Here, we report small replication-regulating RNAs (srRNAs) that specifically inhibit DNA replication of the human BK polyomavirus (BKV) in vitro and in vivo. srRNAs from FM3A murine mammary tumor cells were enriched by DNA replication assay-guided fractionation and hybridization to the BKV noncoding control region (NCCR) and synthesized as cDNAs. Selective mutagenesis of the cDNA sequences and their putative targets suggests that the inhibition of BKV DNA replication is mediated by srRNAs binding to the viral NCCR, hindering early steps in the initiation of DNA replication. Ectopic expression of srRNAs in human cells inhibited BKV DNA replication in vivo. Additional srRNAs were designed and synthesized that specifically inhibit simian virus 40 (SV40) DNA replication in vitro. These observations point to novel mechanisms for regulating DNA replication and suggest the design of synthetic agents for inhibiting replication of polyomaviruses and possibly other viruses.",,"['Tikhanovich, Irina', 'Liang, Bo', 'Seoighe, Cathal', 'Folk, William R.', 'Nasheuer, Heinz Peter']",,,,
,PMC,Diverse Peptide Presentation of Rhesus Macaque Major Histocompatibility Complex Class I Mamu-A*02 Revealed by Two Peptide Complex Structures and Insights into Immune Escape of Simian Immunodeficiency Virus,http://dx.doi.org/10.1128/JVI.00350-11,PMC3126565,,,"Major histocompatibility complex class I (MHC I)-restricted CD8(+) T-cell responses play a pivotal role in anti-human immunodeficiency virus (HIV) immunity and the control of viremia. The rhesus macaque is an important animal model for HIV-related research. Among the MHC I alleles of the rhesus macaque, Mamu-A*02 is prevalent, presenting in ≥20% of macaques. In this study, we determined the crystal structure of Mamu-A*02, the second structure-determined MHC I from the rhesus macaque after Mamu-A*01. The peptide presentation characteristics of Mamu-A*02 are exhibited in complex structures with two typical Mamu-A*02-restricted CD8(+) T-cell epitopes, YY9 (Nef159 to -167; YTSGPGIRY) and GY9 (Gag71 to -79; GSENLKSLY), derived from simian immunodeficiency virus (SIV). These two peptides utilize similar primary anchor residues (Ser or Thr) at position 2 and Tyr at position 9. However, the central region of YY9 is different from that of GY9, a difference that may correlate with the immunogenic variance of these peptides. Further analysis indicated that the distinct conformations of these two peptides are modulated by four flexible residues in the Mamu-A*02 peptide-binding groove. The rare combination of these four residues in Mamu-A*02 leads to a variant presentation for peptides with different residues in their central regions. Additionally, in the two structures of the Mamu-A*02 complex, we compared the binding of rhesus and human β(2) microglobulin (β(2)m) to Mamu-A*02. We found that the peptide presentation of Mamu-A*02 is not affected by the interspecies interaction with human β(2)m. Our work broadens the understanding of CD8(+) T-cell-specific immunity against SIV in the rhesus macaque.",,"['Liu, Jun', 'Dai, Lianpan', 'Qi, Jianxun', 'Gao, Feng', 'Feng, Youjun', 'Liu, Wenjun', 'Yan, Jinghua', 'Gao, George F.']",,,,
,PMC,Virally Expressed Interleukin-10 Ameliorates Acute Encephalomyelitis and Chronic Demyelination in Coronavirus-Infected Mice,http://dx.doi.org/10.1128/JVI.00510-11,PMC3126551,,,"The absence of interleukin-10 (IL-10), a potent anti-inflammatory cytokine results in increased immune-mediated demyelination in mice infected with a neurotropic coronavirus (recombinant J2.2-V-1 [rJ2.2]). Here, we examined the therapeutic effects of increased levels of IL-10 at early times after infection by engineering a recombinant J2.2 virus to produce IL-10. We demonstrate that viral expression of IL-10, which occurs during the peak of virus replication and at the site of disease, enhanced survival and diminished morbidity in rJ2.2-infected wild-type B6 and IL-10(−/−) mice. The protective effects of increased IL-10 levels were associated with reductions in microglial activation, inflammatory cell infiltration into the brain, and proinflammatory cytokine and chemokine production. Additionally, IL-10 increased both the frequency and number of Foxp3(+) regulatory CD4 T cells in the infected central nervous system. Most strikingly, the ameliorating effects of IL-10 produced during the first 5 days after infection were long acting, resulting in decreased demyelination during the resolution phase of the infection. Collectively, these results suggest that the pathogenic processes that result in demyelination are initiated early during infection and that they can be diminished by exogenous IL-10 delivered soon after disease onset. IL-10 functions by dampening the innate or very early T cell immune response. Further, they suggest that early treatment with IL-10 may be useful adjunct therapy in some types of viral encephalitis.",,"['Trandem, Kathryn', 'Jin, Qiushuang', 'Weiss, Kayla A.', 'James, Britnie R.', 'Zhao, Jingxian', 'Perlman, Stanley']",,,,
,PMC,"Canine Distemper Virus Matrix Protein Influences Particle Infectivity, Particle Composition, and Envelope Distribution in Polarized Epithelial Cells and Modulates Virulence",http://dx.doi.org/10.1128/JVI.00051-11,PMC3126548,,,"In paramyxoviruses, the matrix (M) protein mediates the interaction between the envelope and internal proteins during particle assembly and egress. In measles virus (MeV), M mutations, such as those found in subacute sclerosing panencephalitis (SSPE) strains, and differences in vaccine and wild-type M proteins can affect the strength of interaction with the envelope glycoproteins, assembly efficiency, and spread. However, the contribution of the M protein to the replication and pathogenesis of the closely related canine distemper virus (CDV) has not been characterized. To this end this, we generated a recombinant wild-type CDV carrying a vaccine strain M protein. The recombinant virus retained the parental growth phenotype in VerodogSLAMtag cells, but displayed an increased particle-to-infectivity ratio very similar to that of the vaccine strain, likely due to inefficient H protein incorporation. Even though infectious virus was released only from the apical surface, consistent with the release polarity of the wild-type CDV strain, envelope protein distribution in polarized epithelial cells reproduced the bipolar pattern seen in vaccine strain-infected cells. Most notably, the chimeric virus was completely attenuated in ferrets and caused only a mild and transient leukopenia, indicating that the differences in particle infectivity and envelope protein sorting mediated by the vaccine M protein contribute importantly to vaccine strain attenuation.",,"['Dietzel, Erik', 'Anderson, Danielle E.', 'Castan, Alexandre', 'von Messling, Veronika', 'Maisner, Andrea']",,,,
,PMC,Human Herpesvirus 6 Suppresses T Cell Proliferation through Induction of Cell Cycle Arrest in Infected Cells in the G(2)/M Phase,http://dx.doi.org/10.1128/JVI.02577-10,PMC3126536,,,"Human herpesvirus 6 (HHV-6) is an important immunosuppressive and immunomodulatory virus that primarily infects immune cells and strongly suppresses the proliferation of infected cells. However, the mechanisms responsible for the regulation and suppression mediated by HHV-6 are still unknown. In this study, we examined the ability of HHV-6A to manipulate cell cycle progression in infected cells and explored the potential molecular mechanisms. We demonstrated that infection with HHV-6A imposed a growth-inhibitory effect on HSB-2 cells by inducing cell cycle arrest at the G(2)/M phase. We then showed that the activity of the Cdc2–cyclin B1 complex was significantly decreased in HHV-6A-infected HSB-2 cells. Furthermore, we found that inactivation of Cdc2–cyclin B1 in HHV-6A-infected cells occurred through the inhibitory Tyr15 phosphorylation resulting from elevated Wee1 expression and inactivated Cdc25C. The reduction of Cdc2–cyclin B1 activity in HHV-6-infected cells was also partly due to the increased expression of the cell cycle-regulatory molecule p21 in a p53-dependent manner. In addition, HHV-6A infection activated the DNA damage checkpoint kinases Chk2 and Chk1. Our data suggest that HHV-6A infection induces G(2)/M arrest in infected T cells via various molecular regulatory mechanisms. These results further demonstrate the potential mechanisms involved in immune suppression and modulation mediated by HHV-6 infection, and they provide new insights relevant to the development of novel vaccines and immunotherapeutic approaches.",,"['Li, Lingyun', 'Gu, Bin', 'Zhou, Feng', 'Chi, Jing', 'Wang, Fang', 'Peng, Guangyong', 'Xie, Fangyi', 'Qing, Jian', 'Feng, Dongju', 'Lu, Shiqiang', 'Yao, Kun']",,,,
,PMC,CXCR3-Dependent Plasma Blast Migration to the Central Nervous System during Viral Encephalomyelitis,http://dx.doi.org/10.1128/JVI.00202-11,PMC3126522,,,"Immunoglobulin in cerebral spinal fluid and antibody secreting cells (ASC) within the central nervous system (CNS) parenchyma are common hallmarks of microbial infections and autoimmune disorders. However, the signals directing ASC migration into the inflamed CNS are poorly characterized. This study demonstrates that CXCR3 mediates CNS accumulation of ASC during neurotropic coronavirus-induced encephalomyelitis. Expansion of CXCR3-expressing ASC in draining lymph nodes prior to accumulation within the CNS was consistent with their recruitment by sustained expression of CXCR3 ligands during viral persistence. Both total and virus-specific ASC were reduced greater than 80% in the CNS of infected CXCR3(−/−) mice. Similar T cell CNS recruitment and local T cell-dependent antiviral activity further indicated that the ASC migration defect was T cell independent. Furthermore, in contrast to the reduction of ASC in the CNS, neither virus-specific ASC trafficking to bone marrow nor antiviral serum antibody was reduced relative to levels in control mice. Impaired ASC recruitment into the CNS of infected CXCR3(−/−) mice coincided with elevated levels of persisting viral RNA, sustained infectious virus, increased clinical disease, and mortality. These results demonstrate that CXCR3 ligands are indispensable for recruitment of activated ASC into the inflamed CNS and highlight their local protective role during persistent infection.",,"['Marques, Cristina P.', 'Kapil, Parul', 'Hinton, David R.', 'Hindinger, Claudia', 'Nutt, Stephen L.', 'Ransohoff, Richard M.', 'Phares, Timothy W.', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.']",,,,
,PMC,Blocking eIF4E-eIF4G Interaction as a Strategy To Impair Coronavirus Replication,http://dx.doi.org/10.1128/JVI.00078-11,PMC3126520,,,"Coronaviruses are a family of enveloped single-stranded positive-sense RNA viruses causing respiratory, enteric, and neurologic diseases in mammals and fowl. Human coronaviruses are recognized to cause up to a third of common colds and are suspected to be involved in enteric and neurologic diseases. Coronavirus replication involves the generation of nested subgenomic mRNAs (sgmRNAs) with a common capped 5′ leader sequence. The translation of most of the sgmRNAs is thought to be cap dependent and displays a requirement for eukaryotic initiation factor 4F (eIF4F), a heterotrimeric complex needed for the recruitment of 40S ribosomes. We recently reported on an ultrahigh-throughput screen to discover compounds that inhibit eIF4F activity by blocking the interaction of two of its subunits (R. Cencic et al., Proc. Natl. Acad. Sci. U. S. A. 108:1046–1051, 2011). Herein we describe a molecule from this screen that prevents the interaction between eIF4E (the cap-binding protein) and eIF4G (a large scaffolding protein), inhibiting cap-dependent translation. This inhibitor significantly decreased human coronavirus 229E (HCoV-229E) replication, reducing the percentage of infected cells and intra- and extracellular infectious virus titers. Our results support the strategy of targeting the eIF4F complex to block coronavirus infection.",,"['Cencic, Regina', 'Desforges, Marc', 'Hall, David R.', 'Kozakov, Dima', 'Du, Yuhong', 'Min, Jaeki', 'Dingledine, Raymond', 'Fu, Haian', 'Vajda, Sandor', 'Talbot, Pierre J.', 'Pelletier, Jerry']",,,,
,PMC,Shifting Hierarchies of Interleukin-10-Producing T Cell Populations in the Central Nervous System during Acute and Persistent Viral Encephalomyelitis,http://dx.doi.org/10.1128/JVI.00200-11,PMC3126516,,,"Interleukin-10 (IL-10) mRNA is rapidly upregulated in the central nervous system (CNS) following infection with neurotropic coronavirus and remains elevated during persistent infection. Infection of transgenic IL-10/green fluorescent protein (GFP) reporter mice revealed that CNS-infiltrating T cells were the major source of IL-10, with minimal IL-10 production by macrophages and resident microglia. The proportions of IL-10-producing cells were initially similar in CD8(+) and CD4(+) T cells but diminished rapidly in CD8(+) T cells as the virus was controlled. Overall, the majority of IL-10-producing CD8(+) T cells were specific for the immunodominant major histocompatibility complex (MHC) class I epitope. Unlike CD8(+) T cells, a large proportion of CD4(+) T cells within the CNS retained IL-10 production throughout persistence. Furthermore, elevated frequencies of IL-10-producing CD4(+) T cells in the spinal cord supported preferential maintenance of IL-10 production at the site of viral persistence and tissue damage. IL-10 was produced primarily by the CD25(+) CD4(+) T cell subset during acute infection but prevailed in CD25(−) CD4(+) T cells during the transition to persistent infection and thereafter. Overall, these data demonstrate significant fluidity in the T-cell-mediated IL-10 response during viral encephalitis and persistence. While IL-10 production by CD8(+) T cells was limited primarily to the time of acute effector function, CD4(+) T cells continued to produce IL-10 throughout infection. Moreover, a shift from predominant IL-10 production by CD25(+) CD4(+) T cells to CD25(−) CD4(+) T cells suggests that a transition to nonclassical regulatory T cells precedes and is retained during CNS viral persistence.",,"['Puntambekar, Shweta S.', 'Bergmann, Cornelia C.', 'Savarin, Carine', 'Karp, Christopher L.', 'Phares, Timothy W.', 'Parra, Gabriel I.', 'Hinton, David R.', 'Stohlman, Stephen A.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.05082-11,PMC3126504,,,,,,,,,
,PMC,"Entry of Tiger Frog Virus (an Iridovirus) into HepG2 Cells via a pH-Dependent, Atypical, Caveola-Mediated Endocytosis Pathway",http://dx.doi.org/10.1128/JVI.01500-10,PMC3126490,,,"Tiger frog virus (TFV), in the genus Ranavirus of the family Iridoviridae, causes high mortality of cultured tiger frog tadpoles in China. To explore the cellular entry mechanism of TFV, HepG2 cells were treated with drugs that inhibit the main endocytic pathways. We observed that TFV entry was inhibited by NH(4)Cl, chloroquine, and bafilomycin, which can all elevate the pH of acidic organelles. In contrast, TFV entry was not influenced by chlorpromazine or overexpression of a dominant-negative form of Esp15, which inhibit the assembly of clathrin-coated pits. These results suggested that TFV entry was not associated with clathrin-mediated endocytosis, but was related to the pH of acidic organelles. Subsequently, we found that endocytosis of TFV was dependent on membrane cholesterol and was inhibited by the caveolin-1 scaffolding domain peptide. Dynamin and actin were also required for TFV entry. In addition, TFV virions colocalized with the cholera toxin subunit B, indicating that TFV enters as caveola-internalized cargo into the Golgi complex. Taken together, our results demonstrated that TFV entry occurs by caveola-mediated endocytosis with a pH-dependent step. This atypical caveola-mediated endocytosis is different from the clathrin-mediated endocytosis of frog virus 3 (FV3) by BHK cells, which has been recognized as a model for iridoviruses. Thus, our work may help further the understanding of the initial steps of iridovirus infection in lower vertebrates.",,"['Guo, Chang-Jun', 'Liu, Dong', 'Wu, Yan-Yan', 'Yang, Xiao-Bo', 'Yang, Li-Shi', 'Mi, Shu', 'Huang, Yu-Xin', 'Luo, Yong-Wen', 'Jia, Kun-Tong', 'Liu, Zhao-Yu', 'Chen, Wei-Jian', 'Weng, Shao-Ping', 'Yu, Xiao-Qiang', 'He, Jian-Guo']",,,,
,PMC,A single mutation turns a non-binding germline-like predecessor of broadly neutralizing antibody into a binding antibody to HIV-1 envelope glycoproteins,http://dx.doi.org/10.4161/mabs.3.4.15740,PMC3218537,,,"Broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV)-1 are rare in natural infection and elicitation of HIV-1 bnAbs has not been achieved by any vaccine candidates. We and others have reported that HIV-1 bnAbs are highly diversified from their germline-like predecessors and the germline-like predecessors of bnAbs lack measurable binding to HIV-1 envelope (Env) glycoproteins, suggesting that Env structures containing the epitopes of bnAbs may not initiate somatic maturation pathway, which may partially explain the rarity of HIV-1 bnAbs. To determine the minimum mutations required for converting non-binding germline-like predecessors to Env-binding antibodies, we started with the bnAb b12 as a prototype and generated six “chimeric” scFv b12 variants by sequentially replacing the heavy chain V-segment (HV), D(J)-segment [HD(J)] in the heavy chain variable region (VH), and the whole light chain variable region (VL) in b12 germline-like predecessor with the mature counterparts. We tested the recombinant scFv variants for binding and neutralizing activities. Results showed that a single point mutation in germline D-segment was enough to convert nonbinding germline-like b12 to an Env-binding antibody. Replacement with either mature HV or mature VL also made the germline-like b12 bind to Env, but none of single segment replacements conferred neutralization ability to the germline antibody. Mature VL in combination with mature HD(J) or mature HV, or both conferred increasing neutralization activity to the germline antibody. However, hybrid scFv, mature VH/germline VL, did not neutralize HIV-1, suggesting the importance of mature VL in neutralizing the virus. These results may have implications for vaccine development.",,"['Yuan, Tingting', 'Li, Jingjing', 'Zhang, Mei-Yun']",,,,
,PMC,Mining human antibody repertoires,http://dx.doi.org/10.4161/mabs.2.4.12187,PMC3180084,,,"Human monoclonal antibodies (mAbs) have become drugs of choice for the management of an increasing number of human diseases. Human antibody repertoires provide a rich source for human mAbs. Here we review the characteristics of natural and non-natural human antibody repertoires and their mining with non-combinatorial and combinatorial strategies. In particular, we discuss the selection of human mAbs from naïve, immune, transgenic and synthetic human antibody repertoires using methods based on hybridoma technology, clonal expansion of peripheral B cells, single-cell PCR, phage display, yeast display and mammalian cell display. Our reliance on different strategies is shifting as we gain experience and refine methods to the efficient generation of human mAbs with superior pharmacokinetic and pharmacodynamic properties.",,"['Beerli, Roger R', 'Rader, Christoph']",,,,
,PMC,Malaysia Collaborates with the New York Academy of Sciences to Develop an Innovation-Based Economy,,PMC3216235,,,"If Malaysia is to become a high-income country by 2020, it will have to transform into a knowledge-based, innovation economy. This goal will be achieved by developing an atmosphere conducive to experimentation and entrepreneurship at home; while reaching out to partners across the globe. One of Malaysia’s newest partnerships is with the New York Academy of Sciences. The Academy has expertise in innovation and higher education and a long history of promoting science, education, and science-based solutions through a global network of scientists, industry-leaders, and policy-makers. Malaysia’s Prime Minister, Dato’ Sri Mohd Najib Tun Abdul Razak, leveraged the Academy’s network to convene a science, technology, and innovation advisory council. This council would provide practical guidance to establish Malaysia as an innovation-based economy. Three initial focus areas, namely palm-oil biomass utilisation, establishment of smart communities, and capacity building in science and engineering, were established to meet short-term and long-term targets.",,"['Wahome, Michel', 'Rubinstein, Ellis']",,,,
,PMC,A review on chemical and biological properties of Cayratia trifolia Linn. (Vitaceae),http://dx.doi.org/10.4103/0973-7847.91117,PMC3263053,22279376,CC BY-NC-SA,"Cayratia trifolia Linn. Domin Syn. Vitis trifolia (Family: Vitaceae) is commonly known as Fox grape in English; Amlabel, Ramchana in Hindi and Amlavetash in Sanskrit. It is native to India, Asia and Australia. It is a perennial climber having trifoliated leaves with 2-3 cm long petioles and ovate to oblong-ovate leaflets. Flowers are small greenish white and brown in color. Fruits are fleshy, juicy, dark purple or black, nearly spherical, about 1 cm in diameter. It is found throughout the hills in India. This perennial climber is also found in the hotter part of India from Jammu and Rajasthan to Assam extending into the peninusular India upto 600 m height. Whole plant of Cayratia trifolia has been reported to contain yellow waxy oil, steroids/terpenoids, flavonoids, tannins upon preliminary phytochemical screening. Leaves contain stilbenes (piceid, reveratrol, viniferin, ampelopsin). Stem, leaves, roots are reported to possess hydrocyanic acid, delphinidin and several flavonoids such as cyanidin is reported in the leaves. This plant also contains kaempferol, myricetin, quercetin, triterpenes and epifriedelanol. Infusion of seeds along with extract of tubers is traditionally given orally to diabetic patients to check sugar level of blood. Paste of tuberous is applied on the affected part in the treatment of snake bite. Whole plant is used as diuretic, in tumors, neuralgia and splenopathy. Its climbers wrapped around the neck of frantic bullock and poultice of leaves are used to yoke sores of bullock. The bark extract shows the antiviral, antibacterial, antiprotozoal, hypoglycemic, anticancer and diuretic activity. This article focuses on the upgraded review on chemical and biological properties of Cayratia trifolia Linn. and triggers further investigation on this plant.",2011 Jul-Dec,"['Kumar, Dinesh', 'Kumar, Sunil', 'Gupta, Jyoti', 'Arya, Renu', 'Gupta, Ankit']",Pharmacogn Rev,,,
,PMC,"Programmed ribosomal frameshifting in the expression of the regulator of intestinal stem cell proliferation, adenomatous polyposis coli (APC)",http://dx.doi.org/10.4161/rna.8.4.15395,PMC3225980,,,"A programmed ribosomal frameshift (PRF) in the decoding of APC (adenomatous polyposis coli) mRNA has been identified and characterized in caenorhabditis worms, Drosophila and mosquitoes. The frameshift product lacks the C-terminal approximately one-third of the product of standard decoding and instead has a short sequence encoded by the -1 frame which is just 13 residues in C. elegans, but is 125 in D. melanogaster. The frameshift site is A AAA AAC in Caenorhabditids, fruit flies and the mosquitoes studied while a variant A AAA AAA is found in some other nematodes. The predicted secondary RNA structure of the downstream stimulators varies considerably in the species studied. In the twelve sequenced Drosophila genomes, it is a long stem with a four-way junction in its loop. In the five sequenced Caenorhabditis species, it is a short RNA pseudoknot with an additional stem in loop 1. The efficiency of frameshifting varies significantly, depending on the particular stimulator within the frameshift cassette, when tested with reporter constructs in rabbit reticulocyte lysates. Phylogenetic analysis of the distribution of APC programmed ribosomal frameshifting cassettes suggests it has an ancient origin and raises questions about the possibility of synthesis of alternative protein products during expression of APC in other organisms such as humans. The origin of APC as a PRF candidate emerged from a prior study of evolutionary signatures derived from comparative analysis of the 12 fly genomes. Three other proposed PRF candidates (Xbp1, CG32736, CG14047) with switches in conservation of reading frames are likely explained by mechanisms other than PRF.",,"['Baranov, Pavel V', 'Wills, Norma M', 'Barriscale, Kathy A', 'Firth, Andrew E', 'Jud, Molly C', 'Letsou, Anthea', 'Manning, Gerard', 'Atkins, John F']",,,,
,PMC,Strategies for viral RNA stability: live long and prosper,http://dx.doi.org/10.1016/j.tig.2011.04.003,PMC3123725,,,"Eukaryotic cells have a powerful RNA decay machinery that plays important and diverse roles in regulating both the quantity and quality of gene expression. Viral RNAs need to successfully navigate around this cellular machinery in order to initiate and maintain a highly productive infection. Recent work shows that viruses have developed a variety of strategies to accomplish this, including inherent RNA shields, hijacking host RNA stability factors, incapacitating the host decay machinery, and by changing the entire landscape of RNA stability in cells using virally-encoded nucleases. In addition to maintaining the stability of viral transcripts, these strategies can also contribute to the regulation and complexity of viral gene expression, as well as viral RNA evolution.",,"['Dickson, Alexa M.', 'Wilusz, Jeffrey']",,,,
,PMC,"Expression, crystallization and preliminary crystallographic study of the C-terminal half of nsp2 from SARS coronavirus",http://dx.doi.org/10.1107/S1744309111017829,PMC3144797,,,"SARS coronavirus (SARS-CoV) is the aetiological agent of the highly infectious severe acute respiratory syndrome (SARS). To gain a better understanding of SARS-CoV replication and transcription proteins, a preliminary X-ray crystallo­graphic study of the C-terminal domain of SARS-CoV nonstructural protein 2 (nsp2) is reported here. The C-­terminal domain of SARS-CoV nsp2 was cloned, overexpressed, purified and crystallized using polyethylene glycol 5000 monomethyl ether as the precipitant; the crystals diffracted to 2.5 Å resolution. The crystals belonged to space group P6(5), with unit-cell parameters a = b = 112.8, c = 91.1 Å, α = β = 90, γ = 120°. One molecule is assumed to be present per asymmetric unit, which gives a Matthews coefficient of 2.89 Å(3) Da(−1) and a solvent content of 56.2%.",,"['Li, Yuanyuan', 'Ren, Zhilin', 'Bao, Zehua', 'Ming, Zhenhua', 'Li, Xuemei']",,,,
,PMC,Suppression of cytokine storm with a sphingosine analog provides protection against pathogenic influenza virus,http://dx.doi.org/10.1073/pnas.1107024108,PMC3142000,,,"Human pandemic H1N1 2009 influenza virus rapidly infected millions worldwide and was associated with significant mortality. Antiviral drugs that inhibit influenza virus replication are the primary therapy used to diminish disease; however, there are two significant limitations to their effective use: (i) antiviral drugs exert selective pressure on the virus, resulting in the generation of more fit viral progeny that are resistant to treatment; and (ii) antiviral drugs do not directly inhibit immune-mediated pulmonary injury that is a significant component of disease. Here we show that dampening the host's immune response against influenza virus using an immunomodulatory drug, AAL-R, provides significant protection from mortality (82%) over that of the neuraminidase inhibitor oseltamivir alone (50%). AAL-R combined with oseltamivir provided maximum protection against a lethal challenge of influenza virus (96%). Mechanistically, AAL-R inhibits cellular and cytokine/chemokine responses to limit immunopathologic damage, while maintaining host control of virus replication. With cytokine storm playing a role in the pathogenesis of a wide assortment of viral, bacterial, and immunologic diseases, a therapeutic approach using sphingosine analogs is of particular interest.",,"['Walsh, Kevin B.', 'Teijaro, John R.', 'Wilker, Peter R.', 'Jatzek, Anna', 'Fremgen, Daniel M.', 'Das, Subash C.', 'Watanabe, Tokiko', 'Hatta, Masato', 'Shinya, Kyoko', 'Suresh, Marulasiddappa', 'Kawaoka, Yoshihiro', 'Rosen, Hugh', 'Oldstone, Michael B. A.']",,,,
,PMC,Nucleic acid-based nanoengineering: novel structures for biomedical applications,http://dx.doi.org/10.1098/rsfs.2011.0040,PMC3262286,,,"Nanoengineering exploits the interactions of materials at the nanometre scale to create functional nanostructures. It relies on the precise organization of nanomaterials to achieve unique functionality. There are no interactions more elegant than those governing nucleic acids via Watson–Crick base-pairing rules. The infinite combinations of DNA/RNA base pairs and their remarkable molecular recognition capability can give rise to interesting nanostructures that are only limited by our imagination. Over the past years, creative assembly of nucleic acids has fashioned a plethora of two-dimensional and three-dimensional nanostructures with precisely controlled size, shape and spatial functionalization. These nanostructures have been precisely patterned with molecules, proteins and gold nanoparticles for the observation of chemical reactions at the single molecule level, activation of enzymatic cascade and novel modality of photonic detection, respectively. Recently, they have also been engineered to encapsulate and release bioactive agents in a stimulus-responsive manner for therapeutic applications. The future of nucleic acid-based nanoengineering is bright and exciting. In this review, we will discuss the strategies to control the assembly of nucleic acids and highlight the recent efforts to build functional nucleic acid nanodevices for nanomedicine.",,"['Li, Hanying', 'LaBean, Thomas H.', 'Leong, Kam W.']",,,,
,PMC,Tumor Necrosis Factor Receptor 1 Mediates Dendritic Cell Maturation and CD8 T Cell Response through Two Distinct Mechanisms,http://dx.doi.org/10.4049/jimmunol.1002902,PMC3380805,,,"Tumor necrosis factor alpha (TNFα) and its two receptors (TNFR1 and 2) are known to stimulate dendritic cell (DC) maturation and T cell response. However, the specific receptor and mechanisms involved in vivo are still controversial. Here we show that in response to an attenuated mouse hepatitis virus (MHV) infection, DCs fail to mobilize and up-regulate CD40, CD80, CD86, and MHC class I in TNFR1(−/−) mice as compared to the wild-type and TNFR2(−/−) mice. Correspondingly, virus-specific CD8 T cell response was dramatically diminished in TNFR1(−/−) mice. Adoptive transfer of TNFR1-expressing DCs into TNFR1(−/−) mice rescues CD8 T cell response. Interestingly, adoptive transfer of TNFR1-expressing naïve T cells also restores DC mobilization and maturation and endogenous CD8 T cell response. These results show that TNFR1, not TNFR2, mediates TNFα stimulation of DC maturation and T cell response to MHV in vivo. They also suggest two mechanisms by which TNFR1 mediates TNFα-driven DC maturation: a direct effect through TNFR1 expressed on immature DCs and an indirect effect through TNFR1 expressed on naïve T cells.",,"['Ding, Xilai', 'Yang, Wei', 'Shi, Xiaodong', 'Du, Peishuang', 'Su, Lishan', 'Qin, Zhihai', 'Chen, Jianzhu', 'Deng, Hongyu']",,,,
,PMC,Purifying Selection Can Obscure the Ancient Age of Viral Lineages,http://dx.doi.org/10.1093/molbev/msr170,PMC3247791,,,"Statistical methods for molecular dating of viral origins have been used extensively to infer the time of most common recent ancestor for many rapidly evolving pathogens. However, there are a number of cases, in which epidemiological, historical, or genomic evidence suggests much older viral origins than those obtained via molecular dating. We demonstrate how pervasive purifying selection can mask the ancient origins of recently sampled pathogens, in part due to the inability of nucleotide-based substitution models to properly account for complex patterns of spatial and temporal variability in selective pressures. We use codon-based substitution models to infer the length of branches in viral phylogenies; these models produce estimates that are often considerably longer than those obtained with traditional nucleotide-based substitution models. Correcting the apparent underestimation of branch lengths suggests substantially older origins for measles, Ebola, and avian influenza viruses. This work helps to reconcile some of the inconsistencies between molecular dating and other types of evidence concerning the age of viral lineages.",,"['Wertheim, Joel O.', 'Kosakovsky Pond, Sergei L.']",,,,
,PMC,Identification of a Putative Crimean-Congo Hemorrhagic Fever Virus Entry Factor,http://dx.doi.org/10.1016/j.bbrc.2011.06.109,PMC3155881,,,"Entry of enveloped viruses into cells is initiated by binding of their envelope glycoproteins (Envs) to cell surface-associated receptors. The Crimean-Congo hemorrhagic fever virus (CCHFV) has two Envs, Gn and Gc, with poorly understood role in binding to susceptible cells. We expressed codon optimized Gn and Gc, and identified independently folded soluble Env fragments, one of which (Gc residues 180-300) bound CCHFV susceptible cells supposedly by interacting with a putative receptor. This receptor binding domain (RBD) was used to identify its interacting partner by coimmunoprecipitation and mass spectrometry. Thus we identified the human cell surface nucleolin as a putative CCHFV entry factor. Nucleolin was expressed on all susceptible cells tested but not on the surface of cells resistant to CCHFV infection. Further studies are needed to explore the nucleolin function as a plausible CCHFV receptor and the molecular mechanisms of the Gc-nucleolin interactions. The identification of the CCHFV RBD and its binding partner could provide novel targets for therapy and tools for prevention as well as more complete understanding of the mechanisms of CCHFV entry and pathogenesis.",,"['Xiao, Xiaodong', 'Feng, Yang', 'Zhu, Zhongyu', 'Dimitrov, Dimiter S.']",,,,
,PMC,New sources of drugs for hematologic malignancies,http://dx.doi.org/10.1182/blood-2011-02-315283,PMC3357971,,,"Advancing novel therapeutic agents for the treatment of malignancy into the marketplace is an increasingly costly and lengthy process. As such, new strategies for drug discovery are needed. Drug repurposing represents an opportunity to rapidly advance new therapeutic strategies into clinical trials at a relatively low cost. Known on-patent or off-patent drugs with unrecognized anticancer activity can be rapidly advanced into clinical testing for this new indication by leveraging their known pharmacology, pharmacokinetics, and toxicology. Using this approach, academic groups can participate in the drug discovery field and smaller biotechnology companies can “de-risk” early-stage drug discovery projects. Here, several scientific approaches used to identify drug repurposing opportunities are highlighted, with a focus on hematologic malignancies. In addition, a discussion of the regulatory issues that are unique to drug repurposing and how they impact developing old drugs for new indications is included. Finally, the mechanisms to enhance drug repurposing through increased collaborations between academia, industry, and nonprofit charitable organizations are discussed.",,"['Sukhai, Mahadeo A.', 'Spagnuolo, Paul A.', 'Weir, Scott', 'Kasper, James', 'Patton, Lavonne', 'Schimmer, Aaron D.']",,,,
,PMC,Global Health Governance at a Crossroads,,PMC3983705,,,"This review takes stock of the global health governance (GHG) literature. We address the transition from international health governance (IHG) to global health governance, identify major actors, and explain some challenges and successes in GHG. We analyze the framing of health as national security, human security, human rights, and global public good, and the implications of these various frames. We also establish and examine from the literature GHG’s major themes and issues, which include: 1) persistent GHG problems; 2) different approaches to tackling health challenges (vertical, horizontal, and diagonal); 3) health’s multisectoral connections; 4) neoliberalism and the global economy; 5) the framing of health (e.g. as a security issue, as a foreign policy issue, as a human rights issue, and as a global public good); 6) global health inequalities; 7) local and country ownership and capacity; 8) international law in GHG; and 9) research gaps in GHG. We find that decades-old challenges in GHG persist and GHG needs a new way forward. A framework called shared health governance offers promise.",,"['Ng, Nora Y.', 'Ruger, Jennifer Prah']",,,,
,PMC,Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2,http://dx.doi.org/10.1073/pnas.1104760108,PMC3131375,,,"Ebolavirus (Ebov), an enveloped virus of the family Filoviridae, causes hemorrhagic fever in humans and nonhuman primates. The viral glycoprotein (GP) is solely responsible for virus–host membrane fusion, but how it does so remains elusive. Fusion occurs after virions reach an endosomal compartment where GP is proteolytically primed by cathepsins. Fusion by primed GP is governed by an internal fusion loop found in GP2, the fusion subunit. This fusion loop contains a stretch of hydrophobic residues, some of which have been shown to be critical for GP-mediated infection. Here we present liposome fusion data and NMR structures for a complete (54-residue) disulfide-bonded internal fusion loop (Ebov FL) in a membrane mimetic. The Ebov FL induced rapid fusion of liposomes of varying compositions at pH values at or below 5.5. Consistently, circular dichroism experiments indicated that the α-helical content of the Ebov FL in the presence of either lipid-mimetic micelles or small liposomes increases in samples exposed to pH ≤5.5. NMR structures in dodecylphosphocholine micelles at pH 7.0 and 5.5 revealed a conformational change from a relatively flat extended loop structure at pH 7.0 to a structure with an ∼90° bend at pH 5.5. Induction of the bend at low pH reorients and compacts the hydrophobic patch at the tip of the FL. We propose that these changes facilitate disruption of lipids at the site of virus–host cell membrane contact and, hence, initiate Ebov fusion.",,"['Gregory, Sonia M.', 'Harada, Erisa', 'Liang, Binyong', 'Delos, Sue E.', 'White, Judith M.', 'Tamm, Lukas K.']",,,,
,PMC,"Circulating Influenza Virus, Climatic Factors, and Acute Myocardial Infarction: A Time Series Study in England and Wales and Hong Kong",http://dx.doi.org/10.1093/infdis/jir171,PMC3100509,,,"(See the editorial commentary by Finelli and Chaves, on pages 1701-4.) Background. Previous studies identifying associations between influenza and acute cardiac events may have been confounded by climatic factors. Differing seasonal patterns of influenza activity in Hong Kong and England and Wales provide a natural experiment to examine associations with myocardial infarction (MI) independent of cold weather effects. Methods. Weekly clinical and laboratory influenza surveillance data, environmental temperature and humidity data, and counts of MI-associated hospitalizations and deaths were obtained for England and Wales and for Hong Kong for the period 1998–2008. We used Poisson regression models that included environmental and seasonal variables to investigate the relationship between influenza and MI. Results. There were ≥1.2 million MI-associated hospitalizations and 410,204 MI-associated deaths in England and Wales, with a marked peak in the winter season. In Hong Kong, the incidence of MI, on the basis of 65,108 hospitalizations and 18,780 deaths, had a large winter and smaller summer peak, mirroring patterns of influenza activity. There was strong evidence for a link between influenza and MI both in England and Wales, where 3.1%–3.4% of MI-associated deaths (P < .001) and 0.7%–1.2% of MI-associated hospitalizations (P < .001) were attributable to influenza, and in Hong Kong, where the corresponding figures were 3.9%–5.6% (P = .018) and 3.0%–3.3% (P = .002). Conclusions. Influenza was associated with an increase in MI-associated deaths and hospitalizations in 2 contrasting settings.",,"['Warren-Gash, Charlotte', 'Bhaskaran, Krishnan', 'Hayward, Andrew', 'Leung, Gabriel M.', 'Lo, Su-Vui', 'Wong, Chit-Ming', 'Ellis, Joanna', 'Pebody, Richard', 'Smeeth, Liam', 'Cowling, Benjamin J.']",,,,
,PMC,CMAJ 2011 election survey: public health,http://dx.doi.org/10.1503/cmaj.109-3880,PMC3114914,,,,,"Collier, Roger",,,,
,PMC,Type I interferon signaling limits reoviral tropism within the brain and prevents lethal systemic infection,http://dx.doi.org/10.1007/s13365-011-0038-1,PMC3163031,,,"In vivo and ex vivo models of reoviral encephalitis were utilized to delineate the contribution of type I interferon (IFN) to the host’s defense against local central nervous system (CNS) viral infection and systemic viral spread. Following intracranial (i.c.) inoculation with either serotype 3 (T3) or serotype 1 (T1) reovirus, increased expression of IFN-α, IFN-β, and myxovirus-resistance protein (Mx1; a prototypical IFN stimulated gene) was observed in mouse brain tissue. Type I IFN receptor deficient mice (IFNAR(−/−)) had accelerated lethality, compared to wildtype (B6wt) controls, following i.c. T1 or T3 challenge. Although viral titers in the brain and eyes of reovirus infected IFNAR(−/−) mice were significantly increased, these mice did not develop neurologic signs or brain injury. In contrast, increased reovirus titers in peripheral tissues (liver, spleen, kidney, heart, and blood) of IFNAR(−/−) mice were associated with severe intestinal and liver injury. These results suggest that reovirus-infected IFNAR(−/−) mice succumb to peripheral disease rather than encephalitis per se. To investigate the potential role of type I IFN in brain tissue, brain slice cultures (BSCs) were prepared from IFNAR(−/−) mice and B6wt controls for ex vivo T3 reovirus infection. Compared to B6wt controls, reoviral replication and virus-induced apoptosis were enhanced in IFNAR(−/−) BSCs indicating that a type I IFN response, initiated by resident CNS cells, mediates innate viral immunity within the brain. T3 reovirus tropism was extended in IFNAR(−/−) brains to include dentate neurons, ependymal cells, and meningeal cells indicating that reovirus tropism within the CNS is dependent upon type I interferon signaling.",,"['Dionne, Kalen R.', 'Galvin, John M.', 'Schittone, Stephanie A.', 'Clarke, Penny', 'Tyler, Kenneth L.']",,,,
,PMC,Familial aggregation in inflammatory bowel disease: Is it genes or environment?,http://dx.doi.org/10.3748/wjg.v17.i22.2715,PMC3123468,,,"Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD pathogenesis, defining the specific contribution to familial IBD of each one of these factors might have also clinical usefulness. We review the available evidence on familial IBD pathogenesis.",,"['Nunes, Tiago', 'Fiorino, Gionata', 'Danese, Silvio', 'Sans, Miquel']",,,,
,PMC,Crystal structure of mouse coronavirus receptor-binding domain complexed with its murine receptor,http://dx.doi.org/10.1073/pnas.1104306108,PMC3127895,,,"Coronaviruses have evolved diverse mechanisms to recognize different receptors for their cross-species transmission and host-range expansion. Mouse hepatitis coronavirus (MHV) uses the N-terminal domain (NTD) of its spike protein as its receptor-binding domain. Here we present the crystal structure of MHV NTD complexed with its receptor murine carcinoembryonic antigen-related cell adhesion molecule 1a (mCEACAM1a). Unexpectedly, MHV NTD contains a core structure that has the same β-sandwich fold as human galectins (S-lectins) and additional structural motifs that bind to the N-terminal Ig-like domain of mCEACAM1a. Despite its galectin fold, MHV NTD does not bind sugars, but instead binds mCEACAM1a through exclusive protein–protein interactions. Critical contacts at the interface have been confirmed by mutagenesis, providing a structural basis for viral and host specificities of coronavirus/CEACAM1 interactions. Sugar-binding assays reveal that galectin-like NTDs of some coronaviruses such as human coronavirus OC43 and bovine coronavirus bind sugars. Structural analysis and mutagenesis localize the sugar-binding site in coronavirus NTDs to be above the β-sandwich core. We propose that coronavirus NTDs originated from a host galectin and retained sugar-binding functions in some contemporary coronaviruses, but evolved new structural features in MHV for mCEACAM1a binding.",,"['Peng, Guiqing', 'Sun, Dawei', 'Rajashankar, Kanagalaghatta R.', 'Qian, Zhaohui', 'Holmes, Kathryn V.', 'Li, Fang']",,,,
,PMC,Galectin-9 binding to cell surface protein disulfide isomerase regulates the redox environment to enhance T-cell migration and HIV entry,http://dx.doi.org/10.1073/pnas.1017954108,PMC3127870,,,"Interaction of cell surface glycoproteins with endogenous lectins on the cell surface regulates formation and maintenance of plasma membrane domains, clusters signaling complexes, and controls the residency time of glycoproteins on the plasma membrane. Galectin-9 is a soluble, secreted lectin that binds to glycoprotein receptors to form galectin–glycoprotein lattices on the cell surface. Whereas galectin-9 binding to specific glycoprotein receptors induces death of CD4 Th1 cells, CD4 Th2 cells are resistant to galectin-9 death due to alternative glycosylation. On Th2 cells, galectin-9 binds cell surface protein disulfide isomerase (PDI), increasing retention of PDI on the cell surface and altering the redox status at the plasma membrane. Cell surface PDI regulates integrin function on platelets and also enhances susceptibility of T cells to infection with HIV. We find that galectin-9 binding to PDI on Th2 cells results in increased cell migration through extracellular matrix via β3 integrins, identifying a unique mechanism to regulate T-cell migration. In addition, galectin-9 binding to PDI on T cells potentiates infection with HIV. We identify a mechanism for regulating cell surface redox status via a galectin–glycoprotein lattice, to regulate distinct T-cell functions.",,"['Bi, Shuguang', 'Hong, Patrick W.', 'Lee, Benhur', 'Baum, Linda G.']",,,,
,PMC,Characterization of receptors for murine pregnancy specific glycoproteins 17 and 23,http://dx.doi.org/10.1016/j.placenta.2011.05.008,PMC3142296,,,"In primates and rodents, trophoblast cells synthesize and secrete into the maternal circulation a family of proteins known as pregnancy specific glycoproteins (PSG). The current study was undertaken to characterize the receptor for two members of the murine PSG family, PSG17 and PSG23. Binding of recombinant PSG17 and PSG23 to CHO-K1 and L929 cells and their derived mutants was performed to determine whether these proteins bound to cell surface proteoglycans. We also examined binding of these proteins to cells transfected with syndecans and glypican-1 by flow cytometry. The interaction with glycosaminoglycans was confirmed in solid phase assays. Our results show that PSG17 binds to CD9 and to cell surface proteoglycans while PSG23 binds only to the latter. We found that the amino acids involved in CD9 binding reside in the region of highest divergence between the N1-domains of murine PSGs. For both proteins, the N-terminal domain (designated as N1) is sufficient for binding to cells and the ability to bind cell surface proteoglycans is affected by the cell line employed to generate the recombinant proteins. We conclude that while substantially different at the amino acid level, some murine PSGs share with human PSG1 the ability to bind to cell surface proteoglycans and that at least one PSG binds to more than one type of molecule on the cell surface.",,"['Sulkowski, G. N.', 'Warren, J.', 'Ha, C. T.', 'Dveksler, G. S.']",,,,
,PMC,The role of BST2/tetherin in infection with the feline retroviruses,http://dx.doi.org/10.1016/j.vetimm.2011.06.020,PMC4261133,,,"The recently identified host restriction factor tetherin (BST-2, CD317) potently inhibits the release of nascent retrovirus particles from infected cells. Recently, we reported the identification and characterization of tetherin as a novel feline retroviral restriction factor. Based on homology to human tetherin we identified a putative tetherin gene in the genome of the domestic cat (Felis catus) which was found to be expressed in different feline cell lines both prior to and post treatment with either type I or type II interferon (IFN). The predicted structure of feline tetherin (feTHN) was that of a type II single-pass transmembrane protein encoding an N-terminal transmembrane anchor, central predicted coiled-coil bearing extracellular domain to promote dimerization, and a C-terminal GPI-anchor, consistent with conservation of structure between human and feline tetherin. FeTHN displayed potent inhibition of feline immunodeficiency virus (FIV) and human immunodeficiency virus type 1 (HIV-1) particle release in single-cycle replication assays. Notably, feTHN activity was resistant to antagonism by HIV-1 Vpu. However, stable ectopic expression of feTHN mRNA in different feline cell lines had no inhibitory effect on the growth of diverse primary or cell culture-adapted strains of FIV. Hence, whereas feline tetherin efficiently blocks viral particle release in single-cycle replication assays, it might not prevent dissemination of feline retroviruses in vivo.",,"['Dietrich, Isabelle', 'Hosie, Margaret J.', 'Willett, Brian J.']",,,,
,PMC,Immune biology of Ag-specific γδ T cells in infections,http://dx.doi.org/10.1007/s00018-011-0703-9,PMC3593731,,,"Accumulating evidence suggests that human γδ T cells act as non-classical T cells and contribute to both innate and adaptive immune responses in infections. Vγ2 Vδ2 T (also termed Vγ9 Vδ2 T) cells exist only in primates, and in humans represent a dominant circulating γδ T-cell subset. Primate Vγ2 Vδ2 T cells are the only γδ T cell subset capable of recognizing microbial phosphoantigen. Since nonhuman primate Vγ2 Vδ2 T cells resemble their human counterparts, in-depth studies have been undertaken in macaques to understand the biology and function of human Vγ2 Vδ2 T cells. This article reviews the recent progress for immune biology of Vγ2 Vδ2 T cells in infections.",,"Chen, Zheng W.",,,,
,PMC,Regulation of alveolar epithelial cell survival by the ACE-2/angiotensin 1–7/Mas axis,http://dx.doi.org/10.1152/ajplung.00222.2010,PMC3174737,,,"Earlier work from this laboratory demonstrated that apoptosis of alveolar epithelial cells (AECs) requires autocrine generation of angiotensin (ANG) II. More recent studies showed that angiotensin converting enzyme-2 (ACE-2), which degrades ANGII to form ANG1–7, is protective but severely downregulated in human and experimental lung fibrosis. Here it was theorized that ACE-2 and its product ANG1–7 might therefore regulate AEC apoptosis. To evaluate this hypothesis, the AEC cell line MLE-12 and primary cultures of rat AECs were exposed to the profibrotic apoptosis inducers ANGII or bleomycin (Bleo). Markers of apoptosis (caspase-9 or -3 activation and nuclear fragmentation), steady-state ANGII and ANG1–7, and JNK phosphorylation were measured thereafter. In the absence of Bleo, inhibition of ACE-2 by small interfering RNA or by a competitive inhibitor (DX600 peptide) caused a reciprocal increase in autocrine ANGII and corresponding decrease in ANG1–7 in cell culture media (both P < 0.05) and, moreover, induced AEC apoptosis. At baseline (without inhibitor), ANG1–7 in culture media was 10-fold higher than ANGII (P < 0.01). Addition of purified ANGII or bleomycin-induced caspase activation, nuclear fragmentation, and JNK phosphorylation in cultured AECs. However, preincubation with ANG1–7 (0.1 μM) prevented JNK phosphorylation and apoptosis. Moreover, pretreatment with A779, a specific blocker of the ANG1–7 receptor mas, prevented ANG1–7 blockade of JNK phosphorylation, caspase activation, and nuclear fragmentation. These data demonstrate that ACE-2 regulates AEC survival by balancing the proapoptotic ANGII and its antiapoptotic degradation product ANG1–7. They also suggest that ANG1–7 inhibits AEC apoptosis through the ANG1–7 receptor mas.",,"['Uhal, Bruce D.', 'Li, Xiaopeng', 'Xue, Anita', 'Gao, Xu', 'Abdul-Hafez, Amal']",,,,
,PMC,Modeling the Effects of Vaccination and Treatment on Pandemic Influenza,http://dx.doi.org/10.1208/s12248-011-9284-7,PMC3160165,,,"In this paper, we demonstrate the uses of some simple mathematical models for the study of disease dynamics in a pandemic situation with a focus on influenza. These models are employed to evaluate the effectiveness of various control programs via vaccination and antiviral treatment. We use susceptible-, infectious-, recovered-type epidemic models consisting of ordinary differential equations. These models allow us to derive threshold conditions that can be used to assess the effectiveness of vaccine and drug use and to determine disease outcomes. Simulations are helpful for examining the potential consequences of control options under different scenarios. Particularly, results from models with constant parameters and models with time-dependent parameter functions are compared, demonstrating the significant differences in model outcomes. Results suggest that the effectiveness of vaccination and drug treatment can be very sensitive to factors including the time of introduction of the pathogen into the population, the beginning time of control programs, and the levels of control measures. More importantly, in some cases, the benefits of vaccination and antiviral use might be significantly compromised if these control programs are not designed appropriately. Mathematical models can be very useful for understanding the effects of various factors on the spread and control of infectious diseases. Particularly, the models can help identify potential adverse effects of vaccination and drug treatment in the case of pandemic influenza.",,"['Feng, Zhilan', 'Towers, Sherry', 'Yang, Yiding']",,,,
,PMC,CXCR2 Signaling Protects Oligodendrocyte Progenitor Cells from IFN-γ/CXCL10-Mediated Apoptosis,http://dx.doi.org/10.1002/glia.21195,PMC5029281,,,"Infiltration of activated lymphocytes into the central nervous system (CNS) is potentially harmful by damaging resident cells through release of cytokines. Among these is IFN-γ that is secreted by activated natural killer (NK) cells and T lymphocytes and can exert a cytotoxic effect on resident glial populations including oligodendrocytes. Here we show that treatment of mouse oligodendrocyte progenitor cell (OPC)-enriched cultures with IFN-γ resulted in a dose-dependent increase in apoptosis. IFN-γ-induced apoptosis is mediated, in part, through induction of the CXC chemokine ligand 10 (CXCL10; IP-10) from cultured OPCs. Treatment of OPCs with CXCL10 resulted in cell death in a concentration-dependent manner and IFN-γ-treatment of CXCL10−/− OPCs resulted in >50% reduction in cell death. Further, treatment of CXCR3−/− OPC cultures with either IFN-γ or CXCL10 resulted in reduced cell death supporting an important role for CXCL10 signaling in IFN-γ-mediated OPC apoptosis. Data is also provided demonstrating that signaling through CXCR2 protects either IFN-γ or CXCL10-treated OPC cultures from apoptosis and this effect is abolished in CXCR2−/− OPCs. CXCR2-mediated protection from apoptosis is associated with impaired cleavage of caspase 3 and elevated expression of the anti-apoptotic protein Bcl-2. These findings demonstrate a previously unappreciated role for CXCL10 in contributing to neuropathology by promoting oligodendrocyte apoptosis and emphasize the potential relevance in targeting CXCL10 in treating human demyelinating diseases including multiple sclerosis (MS).",,"['TIROTTA, EMANUELE', 'RANSOHOFF, RICHARD M.', 'LANE, THOMAS E.']",,,,
,PMC,Searching for the most cost-effective strategy for controlling epidemics spreading on regular and small-world networks,http://dx.doi.org/10.1098/rsif.2011.0216,PMC3223629,,,"We present a combined epidemiological and economic model for control of diseases spreading on local and small-world networks. The disease is characterized by a pre-symptomatic infectious stage that makes detection and control of cases more difficult. The effectiveness of local (ring-vaccination or culling) and global control strategies is analysed by comparing the net present values of the combined cost of preventive treatment and illness. The optimal strategy is then selected by minimizing the total cost of the epidemic. We show that three main strategies emerge, with treating a large number of individuals (global strategy, GS), treating a small number of individuals in a well-defined neighbourhood of a detected case (local strategy) and allowing the disease to spread unchecked (null strategy, NS). The choice of the optimal strategy is governed mainly by a relative cost of palliative and preventive treatments. If the disease spreads within the well-defined neighbourhood, the local strategy is optimal unless the cost of a single vaccine is much higher than the cost associated with hospitalization. In the latter case, it is most cost-effective to refrain from prevention. Destruction of local correlations, either by long-range (small-world) links or by inclusion of many initial foci, expands the range of costs for which the NS is most cost-effective. The GS emerges for the case when the cost of prevention is much lower than the cost of treatment and there is a substantial non-local component in the disease spread. We also show that local treatment is only desirable if the disease spreads on a small-world network with sufficiently few long-range links; otherwise it is optimal to treat globally. In the mean-field case, there are only two optimal solutions, to treat all if the cost of the vaccine is low and to treat nobody if it is high. The basic reproduction ratio, R(0), does not depend on the rate of responsive treatment in this case and the disease always invades (but might be stopped afterwards). The details of the local control strategy, and in particular the optimal size of the control neighbourhood, are determined by the epidemiology of the disease. The properties of the pathogen might not be known in advance for emerging diseases, but the broad choice of the strategy can be made based on economic analysis only.",,"['Kleczkowski, Adam', 'Oleś, Katarzyna', 'Gudowska-Nowak, Ewa', 'Gilligan, Christopher A.']",,,,
,PMC,"Interferon-gamma, Macrophages, and Virus Spread after HSV-1 Injection",http://dx.doi.org/10.1167/iovs.10-6449,PMC3175943,,,"PURPOSE. After uniocular anterior chamber (AC) injection of HSV-1, the anterior segment of BALB/c mice becomes inflamed and infected; however, virus does not spread from the anterior segment to cause retinitis in the injected eye. The purpose of these studies was to determine whether interferon (IFN-)-γ and Mac-1(+) cells play a role in preventing direct anterior-to-posterior spread of HSV-1 in the injected eye. METHODS. One AC of adult female BALB/c mice was injected with HSV-1 (KOS). The location of IFN-α, IFN-β, and IFN-γ in the injected eye was determined by immunofluorescence, and mRNA expression was quantified by qPCR. Injected eyes of IFN-γ knockout or clodronate-treated macrophage-depleted mice were examined to determine whether the absence of IFN-γ or Mac-1(+) macrophages affected the sites or timing of virus spread. RESULTS. IFN-α, IFN-β, and IFN-γ were observed in the anterior segment of injected eyes through 72 hours and mRNA levels of IFN-β and IFN-γ were increased in virus-infected eyes 48 to 120 hours after infection. However, the absence of IFN-γ or macrophages did not affect either the sites or the timing of HSV-1 infection in injected eyes. CONCLUSIONS. Protection of the retina of the injected eye does not depend on a single cell type or cytokine. In addition, in the eye, as in other sites of the body, there are redundancies in the innate response to virus infection.",,"['Cathcart, Heather M.', 'Zheng, Mei', 'Covar, Jason J.', 'Liu, Yi', 'Podolsky, Robert', 'Atherton, Sally S.']",,,,
,PMC,Negatively charged liposomes show potent adjuvant activity when simply admixed with protein antigens,http://dx.doi.org/10.1021/mp200016d,PMC3148289,,,"Liposomes have been investigated extensively as a vaccine delivery system. Herein the adjuvant activities of liposomes with different net surface charges (neutral, positive, or negative) were evaluated when admixed with protein antigens, ovalbumin (OVA, pI = 4.7), Bacillus anthracis protective antigen protein (PA, pI = 5.6), or cationized OVA (cOVA). Mice immunized subcutaneously with OVA admixed with different liposomes generated different antibody responses. Interestingly, OVA admixed with net negatively charged liposomes prepared with DOPA was as immunogenic as OVA admixed with positively charged liposomes prepared with DOTAP. Immunization of mice with the anthrax PA protein admixed with the net negatively charged DOPA liposomes also induced a strong and functional anti-PA antibody response. When the cationized OVA was used as a model antigen, liposomes with net neutral, negative, or positive charges showed comparable adjuvant activities. Immunization of mice with the OVA admixed with DOPA liposomes also induced OVA-specific CD8(+) cytotoxic T lymphocyte responses and significantly delayed the growth of OVA-expressing B16-OVA tumors in mice. However, not all net negatively charged liposomes showed a strong adjuvant activity. The adjuvant activity of the negatively charged liposomes may be related to the liposome’s ability (i) to up-regulate the expression of molecules related to the activation and maturation of antigen-presenting cells and (ii) to slightly facilitate the uptake of the antigens by antigen-presenting cells. Simply admixing certain negatively charged liposomes with certain protein antigens of interest may represent a novel platform for vaccine development.",,"['Yanasarn, Nijaporn', 'Sloat, Brian R.', 'Cui, Zhengrong']",,,,
,PMC,2′-5′oligoadenylate synthetase 1 (2-5 OAS1) polymorphism is associated with prostate cancer,http://dx.doi.org/10.1002/cncr.26219,PMC3167978,,,"BACKGROUND: 2′ -5′ –oligoadenylate synthetase (2-5 OAS1), an antiviral, pro-apoptotic and anti-proliferative gene converts ATP to a series of 2′ -5′ –oligoadenylates (2-5A). 2-5A in turn activates RNaseL, a candidate hereditary prostate cancer gene. OAS1 polymorphism (rs2660) has been associated with increased susceptibility to infections and various diseases. In general, the low enzyme activity AA genotype promotes susceptibility whereas high enzyme activity GG genotype confers protection. In this study we investigated the association of this functional polymorphism (rs2660) in OAS1 with prostate cancer. METHODS: Sample size and power was calculated using the PGA software. Genomic DNA from a controls (n=140) and prostate cancer patients (n=164) were used for genotyping SNPs rs2660, rs1131454 and rs34137742 on all samples. Statistical analysis was performed using logistic regression model. RESULTS: Significant association was observed between rs2660 genotype (A/G) and prostate cancer. Genotype AA increased the risk whereas GG genotype decreased the risk of prostate cancer. The GG genotype was not observed in the African American samples. The AA genotype also increased the risk of prostate cancer with age. CONCLUSIONS: OAS1 SNP rs2660 AA genotype is significantly associated with prostate cancer whereas GG genotype protects against prostate cancer. OAS1 rs2660 could be a prostate cancer susceptibility polymorphism, a significant observation especially in a context of the OAS1-RNaseL pathway. Thus a functional defect in OAS1 due to rs2660 SNP can not only attenuate RNaseL function, but can also alter cell growth and apoptosis independent of RNaseL.",,"['Mandal, Sanjay', 'Abebe, Fisseha', 'Chaudhary, Jaideep']",,,,
,PMC,Inflammation Induced by Infection Potentiates Tau Pathological Features in Transgenic Mice,http://dx.doi.org/10.1016/j.ajpath.2011.02.012,PMC3124234,,,"Comorbidities that promote the progression of Alzheimer's disease (AD) remain to be uncovered and evaluated in animal models. Because elderly individuals are vulnerable to viral and bacterial infections, these microbial agents may be considered important comorbidities that could potentiate an already existing and tenuous inflammatory condition in the brain, accelerating cognitive decline, particularly if the cellular and molecular mechanisms can be defined. Researchers have recently demonstrated that triggering inflammation in the brain exacerbates tau pathological characteristics in animal models. Herein, we explore whether inflammation induced via viral infection, compared with inflammation induced via bacterial lipopolysaccharide, modulates AD-like pathological features in the 3xTg-AD mouse model and provide evidence to support the hypothesis that infectious agents may act as a comorbidity for AD. Our study shows that infection-induced acute or chronic inflammation significantly exacerbates tau pathological characteristics, with chronic inflammation leading to impairments in spatial memory. Tau phosphorylation was increased via a glycogen synthase kinase-3β–dependent mechanism, and there was a prominent shift of tau from the detergent-soluble to the detergent-insoluble fraction. During chronic inflammation, we found that inhibiting glycogen synthase kinase-3β activity with lithium reduced tau phosphorylation and the accumulation of insoluble tau and reversed memory impairments. Taken together, infectious agents that trigger central nervous system inflammation may serve as a comorbidity for AD, leading to cognitive impairments by a mechanism that involves exacerbation of tau pathological characteristics.",,"['Sy, Michael', 'Kitazawa, Masashi', 'Medeiros, Rodrigo', 'Whitman, Lucia', 'Cheng, David', 'Lane, Thomas E.', 'LaFerla, Frank M.']",,,,
,PMC,The Return of Epidemics and the Politics of Global–Local Health,http://dx.doi.org/10.2105/AJPH.2010.300026,PMC3093284,,,"With fears of global health epidemics (of reemerging infectious diseases) having escalated over the past few decades, we must ask how we understand the diverse responses to such outbreaks. I explore a single event that merits revisiting—the 1994 outbreak of plague in Surat, the commercial capital of the Indian state of Gujarat—in an attempt to answer this question. I trace responses at various intersecting levels of public health and political authority—global, national, and local—as they interacted with each other and expressed specific political concerns and social anxieties during this outbreak.",,"Sivaramakrishnan, Kavita",,,,
,PMC,Ammonia Disinfection of Hatchery Waste for Elimination of Single-Stranded RNA Viruses,http://dx.doi.org/10.1128/AEM.02990-10,PMC3131629,,,"Hatchery waste, an animal by-product of the poultry industry, needs sanitation treatment before further use as fertilizer or as a substrate in biogas or composting plants, owing to the potential presence of opportunistic pathogens, including zoonotic viruses. Effective sanitation is also important in viral epizootic outbreaks and as a routine, ensuring high hygiene standards on farms. This study examined the use of ammonia at different concentrations and temperatures to disinfect hatchery waste. Inactivation kinetics of high-pathogenic avian influenza virus H7N1 and low-pathogenic avian influenza virus H5N3, as representatives of notifiable avian viral diseases, were determined in spiked hatchery waste. Bovine parainfluenza virus type 3, feline coronavirus, and feline calicivirus were used as models for other important avian pathogens, such as Newcastle disease virus, infectious bronchitis virus, and avian hepatitis E virus. Bacteriophage MS2 was also monitored as a stable indicator. Coronavirus was the most sensitive virus, with decimal reduction (D) values of 1.2 and 0.63 h after addition of 0.5% (wt/wt) ammonia at 14 and 25°C, respectively. Under similar conditions, high-pathogenic avian influenza H7N1 was the most resistant, with D values of 3.0 and 1.4 h. MS2 was more resistant than the viruses to all treatments and proved to be a suitable indicator of viral inactivation. The results indicate that ammonia treatment of hatchery waste is efficient in inactivating enveloped and naked single-stranded RNA viruses. Based on the D values and confidence intervals obtained, guidelines for treatment were proposed, and one was successfully validated at full scale at a hatchery, with MS2 added to hatchery waste.",,"['Emmoth, Eva', 'Ottoson, Jakob', 'Albihn, Ann', 'Belák, Sándor', 'Vinnerås, Björn']",,,,
,PMC,Improving the Evidence Base for Decision Making During a Pandemic: The Example of 2009 Influenza A/H1N1,http://dx.doi.org/10.1089/bsp.2011.0007,PMC3102310,,,"This article synthesizes and extends discussions held during an international meeting on “Surveillance for Decision Making: The Example of 2009 Pandemic Influenza A/H1N1,” held at the Center for Communicable Disease Dynamics (CCDD), Harvard School of Public Health, on June 14 and 15, 2010. The meeting involved local, national, and global health authorities and academics representing 7 countries on 4 continents. We define the needs for surveillance in terms of the key decisions that must be made in response to a pandemic: how large a response to mount and which control measures to implement, for whom, and when. In doing so, we specify the quantitative evidence required to make informed decisions. We then describe the sources of surveillance and other population-based data that can presently—or in the future—form the basis for such evidence, and the interpretive tools needed to process raw surveillance data. We describe other inputs to decision making besides epidemiologic and surveillance data, and we conclude with key lessons of the 2009 pandemic for designing and planning surveillance in the future.",,"['Lipsitch, Marc', 'Finelli, Lyn', 'Heffernan, Richard T.', 'Leung, Gabriel M.', 'Redd, Stephen C.']",,,,
,PMC,Rhinovirus-associated wheeze during infancy and asthma development,,PMC3469323,,,"Rhinovirus is commonly associated with bronchiolitis - only second to RSV during the first year life. The prevalence of HRV-bronchiolitis may be very high in predisposed infants. HRV diagnosis is almost exclusively based on PCR, which detects respiratory infections with or without symptoms. Two immunologic factors, interferon responses and atopy, have been associated with susceptibility to HRV-bronchiolitis in multiple studies. The current data supports the hypothesis that susceptibility to HRV-bronchiolitis is likely to be an early manifestation of biased immune responses, which are linked to both decreased viral defence and atopic airway inflammation. Prospective studies have consistently shown that early wheezing associated with HRV infection is closely associated with recurrent wheezing and the development of asthma in children. Collectively, these studies suggest that HRV infection in wheezing children could serve as a clinically useful marker for early identification of asthma prone children. The findings to date provide the rationale for future studies to incorporate rhinovirus illnesses into asthma risk indices.",,"['Jartti, Tuomas', 'Gern, James E.']",,,,
,PMC,"Hendra and Nipah Infection: Pathology, Models and Potential Therapies",,PMC3253017,,,"The Paramyxoviridae family comprises of several genera that contain emerging or re-emerging threats for human and animal health with no real specific effective treatment available. Hendra and Nipah virus are members of a newly identified genus of emerging paramyxoviruses, Henipavirus. Since their discovery in the 1990s, henipaviruses outbreaks have been associated with high economic and public health threat potential. When compared to other paramyxoviruses, henipaviruses appear to have unique characteristics. Henipaviruses are zoonotic paramyxoviruses with a broader tropism than most other paramyxoviruses, and can cause severe acute encephalitis with unique features among viral encephalitides. There are currently no approved effective prophylactic or therapeutic treatments for henipavirus infections. Although ribavirin was empirically used and seemed beneficial during the biggest outbreak caused by one of these viruses, the Nipah virus, its efficacy is disputed in light of its lack of efficacy in several animal models of henipavirus infection. Nevertheless, because of its highly pathogenic nature, much effort has been spent in developing anti-henipavirus therapeutics. In this review we describe the unique features of henipavirus infections and the different strategies and animal models that have been developed so far in order to identify and test potential drugs to prevent or treat henipavirus infections. Some of these components have the potential to be broad-spectrum antivirals as they target effectors of viral pathogenecity common to other viruses. We will focus on small molecules or biologics, rather than vaccine strategies, that have been developed as anti-henipaviral therapeutics.",,"['Vigant, Frederic', 'Lee, Benhur']",,,,
,PMC,The Interplay of mRNA Stimulatory Signals Required for AUU-Mediated Initiation and Programmed −1 Ribosomal Frameshifting in Decoding of Transposable Element IS911,http://dx.doi.org/10.1128/JB.00115-11,PMC3133126,,,"The IS911 bacterial transposable element uses −1 programmed translational frameshifting to generate the protein required for its mobility: translation initiated in one gene (orfA) shifts to the −1 frame and continues in a second overlapping gene (orfB), thus generating the OrfAB transposase. The A-AAA-AAG frameshift site of IS911 is flanked by two stimulatory elements, an upstream Shine-Dalgarno sequence and a downstream stem-loop. We show here that, while they can act independently, these stimulators have a synergistic effect when combined. Mutagenic analyses revealed features of the complex stem-loop that make it a low-efficiency stimulator. They also revealed the dual role of the upstream Shine-Dalgarno sequence as (i) a stimulator of frameshifting, by itself more potent than the stem-loop, and (ii) a mandatory determinant of initiation of OrfB protein synthesis on an AUU codon directly preceding the A6G motif. Both roles rely on transient base pairing of the Shine-Dalgarno sequence with the 3′ end of 16S rRNA. Because of its effect on frameshifting, the Shine-Dalgarno sequence is an important determinant of the level of transposase in IS911-containing cells, and hence of the frequency of transposition.",,"['Prère, Marie-Françoise', 'Canal, Isabelle', 'Wills, Norma M.', 'Atkins, John F.', 'Fayet, Olivier']",,,,
,PMC,Added Value of an Oropharyngeal Swab in Detection of Viruses in Children Hospitalized with Lower Respiratory Tract Infection,http://dx.doi.org/10.1128/JCM.02605-10,PMC3122752,,,"Paired nasopharyngeal and oropharyngeal swabs collected from 533 children hospitalized with lower respiratory tract infection were assessed by multiplex reverse transcription-PCR. Oropharyngeal swabs increased the number of viral infections detected by 15%, compared to collection of a nasopharyngeal swab alone. This advantage was most pronounced for detection of influenza, parainfluenza, and adenovirus.",,"['Hammitt, Laura L.', 'Kazungu, Sidi', 'Welch, Steve', 'Bett, Anne', 'Onyango, Clayton O.', 'Gunson, Rory N.', 'Scott, J. Anthony G.', 'Nokes, D. James']",,,,
,PMC,Application of TaqMan Low-Density Arrays for Simultaneous Detection of Multiple Respiratory Pathogens,http://dx.doi.org/10.1128/JCM.02270-10,PMC3122721,,,"The large and growing number of viral and bacterial pathogens responsible for respiratory infections poses a challenge for laboratories seeking to provide rapid and comprehensive pathogen identification. We evaluated a novel application of the TaqMan low-density array (TLDA) cards for real-time PCR detection of 21 respiratory-pathogen targets. The performance of the TLDA was compared to that of individual real-time PCR (IRTP) assays with the same primers and probes using (i) nucleic acids extracted from the 21 pathogen strains and 66 closely related viruses and bacteria and (ii) 292 clinical respiratory specimens. With spiked samples, TLDA cards were about 10-fold less sensitive than IRTP assays. By using 292 clinical specimens to generate 2,238 paired individual assays, the TLDA card exhibited 89% sensitivity (95% confidence interval [CI], 86 to 92%; range per target, 47 to 100%) and 98% specificity (95% CI, 97 to 99%; range per target, 85 to 100%) overall compared to IRTP assays as the gold standard with a threshold cycle (C(T)) cutoff of 43. The TLDA card approach offers promise for rapid and simultaneous identification of multiple respiratory pathogens for outbreak investigations and disease surveillance.",,"['Kodani, Maja', 'Yang, Genyan', 'Conklin, Laura M.', 'Travis, Tatiana C.', 'Whitney, Cynthia G.', 'Anderson, Larry J.', 'Schrag, Stephanie J.', 'Taylor, Thomas H.', 'Beall, Bernard W.', 'Breiman, Robert F.', 'Feikin, Daniel R.', 'Njenga, M. Kariuki', 'Mayer, Leonard W.', 'Oberste, M. Steven', 'Tondella, Maria Lucia C.', 'Winchell, Jonas M.', 'Lindstrom, Stephen L.', 'Erdman, Dean D.', 'Fields, Barry S.']",,,,
,PMC,Evaluation and Clinical Validation of an Alcohol-Based Transport Medium for Preservation and Inactivation of Respiratory Viruses,http://dx.doi.org/10.1128/JCM.00327-11,PMC3122718,,,"The clinical and public health importance of influenza and other respiratory viruses has accelerated the development of highly sensitive molecular diagnostics, but data are limited regarding preanalytical stages of diagnostic testing. We evaluated CyMol, an alcohol-based transport medium, for its ability to maintain specimen integrity for up to 21 days of storage at various temperatures; for its ability to inactivate virus; and for its compatibility with antigen- or nucleic acid-based diagnostics for respiratory viruses in clinical samples. In mock-infected samples, both universal transport medium (UTM-RT) and CyMol maintained equivalent viral quantities for at least 14 days at room temperature or colder, whereas a dry swab collection maintained viral quantities only if refrigerated or frozen. CyMol inactivated influenza virus within 5 min of sample immersion. UTM-RT- and CyMol-collected nasal swab specimens from 73 symptomatic students attending a campus health clinic were positive for a respiratory virus in 56.2% of subjects by multiplex PCR testing, including influenza A and B viruses, rhinovirus/enteroviruses, coronaviruses, respiratory syncytial virus, parainfluenza viruses, metapneumovirus, and adenovirus. Detection by PCR was equivalent in UTM-RT- and CyMol-collected specimens and in self- and staff-collected swabs. Direct fluorescent antibody (DFA) testing was substantially less sensitive (23.3%) than multiplex PCR, and DFA testing from UTM-RT-collected swabs was more sensitive than that from CyMol-collected swabs. These data indicate that an alcohol-based transport medium such as CyMol preserves respiratory virus integrity, rapidly inactivates viruses, and is compatible with PCR-based respiratory diagnostics.",,"['Luinstra, Kathy', 'Petrich, Astrid', 'Castriciano, Santina', 'Ackerman, Mona', 'Chong, Sylvia', 'Carruthers, Susan', 'Ammons, Brenna', 'Mahony, James B.', 'Smieja, Marek']",,,,
,PMC,Detection of Respiratory Viruses by PCR Assay of Nasopharyngeal Swabs Stored in Skim Milk-Tryptone-Glucose-Glycerol Transport Medium,http://dx.doi.org/10.1128/JCM.00224-11,PMC3122715,,,"We analyzed 129 paired nasopharyngeal aspirates (stored in viral transport medium [VTM]) and nasopharyngeal swabs (stored in skim milk-tryptone-glucose-glycerol [STGG] bacterial transport and storage medium) using PCRs to detect adenoviruses, influenza virus A or B, and respiratory syncytial virus (RSV). Overall, swabs stored in STGG medium without antimicrobials were found to be an acceptable alternative to aspirates stored in antimicrobial-containing VTM, with PCR agreement of 90.2% (kappa of 0.8).",,"['Turner, Paul', 'Po, Linda', 'Turner, Claudia', 'Goldblatt, David', 'Nosten, Francois']",,,,
,PMC,Molecular characterization of a new species in the genus Alphacoronavirus associated with mink epizootic catarrhal gastroenteritis,http://dx.doi.org/10.1099/vir.0.025353-0,PMC3168282,,,"A coronavirus (CoV) previously shown to be associated with catarrhal gastroenteritis in mink (Mustela vison) was identified by electron microscopy in mink faeces from two fur farms in Wisconsin and Minnesota in 1998. A pan-coronavirus and a genus-specific RT-PCR assay were used initially to demonstrate that the newly discovered mink CoVs (MCoVs) were members of the genus Alphacoronavirus. Subsequently, using a random RT-PCR approach, full-genomic sequences were generated that further confirmed that, phylogenetically, the MCoVs belonged to the genus Alphacoronavirus, with closest relatedness to the recently identified but only partially sequenced (fragments of the polymerase, and full-length spike, 3c, envelope, nucleoprotein, membrane, 3x and 7b genes) ferret enteric coronavirus (FRECV) and ferret systemic coronavirus (FRSCV). The molecular data presented in this study provide the first genetic evidence for a new coronavirus associated with epizootic catarrhal gastroenteritis outbreaks in mink and demonstrate that MCoVs possess high genomic variability and relatively low overall nucleotide sequence identities (91.7 %) between contemporary strains. Additionally, the new MCoVs appeared to be phylogenetically distant from human (229E and NL63) and other alphacoronaviruses and did not belong to the species Alphacoronavirus 1. It is proposed that, together with the partially sequenced FRECV and FRSCV, they comprise a new species within the genus Alphacoronavirus.",,"['Vlasova, Anastasia N.', 'Halpin, Rebecca', 'Wang, Shiliang', 'Ghedin, Elodie', 'Spiro, David J.', 'Saif, Linda J.']",,,,
,PMC,Infection with human coronavirus NL63 enhances streptococcal adherence to epithelial cells,http://dx.doi.org/10.1099/vir.0.028381-0,PMC3168281,,,"Understanding the mechanisms of augmented bacterial pathogenicity in post-viral infections is the first step in the development of an effective therapy. This study assessed the effect of human coronavirus NL63 (HCoV-NL63) on the adherence of bacterial pathogens associated with respiratory tract illnesses. It was shown that HCoV-NL63 infection resulted in an increased adherence of Streptococcus pneumoniae to virus-infected cell lines and fully differentiated primary human airway epithelium cultures. The enhanced binding of bacteria correlated with an increased expression level of the platelet-activating factor receptor (PAF-R), but detailed evaluation of the bacterium–PAF-R interaction revealed a limited relevance of this process.",,"['Golda, Anna', 'Malek, Natalia', 'Dudek, Bartosz', 'Zeglen, Slawomir', 'Wojarski, Jacek', 'Ochman, Marek', 'Kucewicz, Ewa', 'Zembala, Marian', 'Potempa, Jan', 'Pyrc, Krzysztof']",,,,
,PMC,Nitric oxide and redox mechanisms in the immune response,http://dx.doi.org/10.1189/jlb.1010550,PMC3100761,,,"The role of redox molecules, such as NO and ROS, as key mediators of immunity has recently garnered renewed interest and appreciation. To regulate immune responses, these species trigger the eradication of pathogens on the one hand and modulate immunosuppression during tissue-restoration and wound-healing processes on the other. In the acidic environment of the phagosome, a variety of RNS and ROS is produced, thereby providing a cauldron of redox chemistry, which is the first line in fighting infection. Interestingly, fluctuations in the levels of these same reactive intermediates orchestrate other phases of the immune response. NO activates specific signal transduction pathways in tumor cells, endothelial cells, and monocytes in a concentration-dependent manner. As ROS can react directly with NO-forming RNS, NO bioavailability and therefore, NO response(s) are changed. The NO/ROS balance is also important during Th1 to Th2 transition. In this review, we discuss the chemistry of NO and ROS in the context of antipathogen activity and immune regulation and also discuss similarities and differences between murine and human production of these intermediates.",,"['Wink, David A.', 'Hines, Harry B.', 'Cheng, Robert Y. S.', 'Switzer, Christopher H.', 'Flores-Santana, Wilmarie', 'Vitek, Michael P.', 'Ridnour, Lisa A.', 'Colton, Carol A.']",,,,
,PMC,Macrophage-Mediated Optic Neuritis Induced by Retrograde Axonal Transport of Spike Gene Recombinant Mouse Hepatitis Virus,http://dx.doi.org/10.1097/NEN.0b013e31821da499,PMC3110774,,,"Following intracranial inoculation, neurovirulent mouse hepatitis virus (MHV) strains induce acute inflammation, demyelination and axonal loss in the CNS. Prior studies using recombinant MHV strains that differ only in the spike gene, which encodes a glycoprotein involved in virus-host cell attachment, demonstrated that spike mediates anterograde axonal transport of virus to the spinal cord. A demyelinating MHV strain induces optic neuritis, but whether this is due to retrograde axonal transport of viral particles to the retina, or if it is due to traumatic disruption of retinal ganglion cell axons during intracranial inoculation is not known. Using recombinant isogenic MHV strains, we examined the ability of recombinant MHV to induce optic neuritis by retrograde spread from the brain through the optic nerve into the eye following intracranial inoculation. Recombinant demyelinating MHV induced macrophage infiltration of optic nerves, demyelination and axonal loss whereas optic neuritis and axonal injury were minimal in mice infected with the non-demyelinating MHV strain that differs in the spike gene. Thus, optic neuritis was dependent on a spike glycoprotein-mediated mechanism of viral antigen transport along retinal ganglion cell axons. These data indicate that MHV spreads by retrograde axonal transport to the eye and that targeting spike protein interactions with axonal transport machinery is a potential therapeutic strategy for CNS viral infections and associated diseases.",,"['Shindler, Kenneth S.', 'Chatterjee, Dhriti', 'Biswas, Kaushiki', 'Goyal, Ashish', 'Dutt, Mahasweta', 'Nassrallah, Mayssa', 'Khan, Reas S.', 'Sarma, Jayasri Das']",,,,
,PMC,A Pre-Immediate-Early Role for Tegument ICP0 in the Proteasome-Dependent Entry of Herpes Simplex Virus,http://dx.doi.org/10.1128/JVI.00267-11,PMC3126318,,,"Herpes simplex virus (HSV) entry requires host cell 26S proteasomal degradation activity at a postpenetration step. When expressed in the infected cell, the HSV immediate-early protein ICP0 has E3 ubiquitin ligase activity and interacts with the proteasome. The cell is first exposed to ICP0 during viral entry, since ICP0 is a component of the inner tegument layer of the virion. The function of tegument ICP0 is unknown. Deletion of ICP0 or mutations in the N-terminal RING finger domain of ICP0 results in the absence of ICP0 from the tegument. We show here that these mutations negatively influenced the targeting of incoming capsids to the nucleus. Inhibitors of the chymotrypsin-like activity of the proteasome the blocked entry of virions containing tegument ICP0, including ICP0 mutants that are defective in USP7 binding. However, ICP0-deficient virions were not blocked by proteasomal inhibitors and entered cells via a proteasome-independent mechanism. ICP0 appeared to play a postpenetration role in cells that supported either endocytosis or nonendosomal entry pathways for HSV. The results suggest that ICP0 mutant virions are defective upstream of viral gene expression at a pre-immediate-early step in infection. We propose that proteasome-mediated degradation of a virion or host protein is regulated by ICP0 to allow efficient delivery of entering HSV capsids to the nuclear periphery.",,"['Delboy, Mark G.', 'Nicola, Anthony V.']",,,,
,PMC,Two Distinct Conformations of a Rinderpest Virus Epitope Presented by Bovine Major Histocompatibility Complex Class I N*01801: a Host Strategy To Present Featured Peptides,http://dx.doi.org/10.1128/JVI.00030-11,PMC3126294,,,"The presentation of viral peptide epitopes to host cytotoxic T lymphocytes (CTLs) is crucial for adaptive cellular immunity to clear the virus infection, especially for some chronic viral infections. Indeed, hosts have developed effective strategies to achieve this goal. The ideal scenario would be that the peptide epitopes stimulate a broad spectrum of CTL responses with diversified T-cell receptor (TCR) usage (the TCR repertoire). It is believed that a diversified TCR repertoire requires a “featured” peptide to be presented by the host major histocompatibility complex (MHC). A featured peptide can be processed and presented in a number of ways. Here, using the X-ray diffraction method, the crystal structures of an antigenic peptide derived from rinderpest virus presented by bovine MHC class I N*01801 (BoLA-A11) have been solved, and two distinct conformations of the presented peptide are clearly displayed. A detailed analysis of the structure and comparative sequences revealed that the polymorphic amino acid isoleucine 73 (Ile73) is extremely flexible, allowing the MHC groove to adopt different conformations to accommodate the rinderpest virus peptide. This makes the peptide more featured by exposing different amino acids for T-cell recognition. The crystal structures also demonstrated that the N*01801 molecule has an unusually large A pocket, resulting in the special conformation of the P1 residue at the N terminus of the peptide. We propose that this strategy of host peptide presentation might be beneficial for creating a diversified TCR repertoire, which is important for a more-effective CTL response.",,"['Li, Xin', 'Liu, Jun', 'Qi, Jianxun', 'Gao, Feng', 'Li, Qirun', 'Li, Xiaoying', 'Zhang, Nianzhi', 'Xia, Chun', 'Gao, George F.']",,,,
,PMC,Identification of a Golgi Complex-Targeting Signal in the Cytoplasmic Tail of the Severe Acute Respiratory Syndrome Coronavirus Envelope Protein,http://dx.doi.org/10.1128/JVI.00060-11,PMC3126292,,,"The 2003 global outbreak of progressive respiratory failure was caused by a newly emerged virus, severe acute respiratory syndrome coronavirus (SARS-CoV). In contrast to many well-studied enveloped viruses that assemble and bud at the plasma membrane, coronaviruses assemble by budding into the lumen of the endoplasmic reticulum-Golgi intermediate compartment and are released from the cell by exocytosis. For this to occur, the viral envelope proteins must be efficiently targeted to the Golgi region of the secretory pathway. Although the envelope protein (E) makes up only a small percentage of the viral envelope, it plays an important, as-yet-undefined role in virus production. To dissect the targeting of the SARS-CoV E protein to the Golgi region, we exogenously expressed the protein and various mutants from cDNA and determined their localization using immunofluorescence microscopy and biochemical assays. We show that the cytoplasmic tail of the SARS-CoV E protein is sufficient to redirect a plasma membrane protein to the Golgi region. Through site-directed mutagenesis, we demonstrate that a predicted beta-hairpin structural motif in the tail is sufficient for Golgi complex localization of a reporter protein. This motif is conserved in E proteins of beta and gamma coronaviruses (formerly referred to as group 2 and 3 coronaviruses), where it also functions as a Golgi complex-targeting signal. Dissecting the mechanism of targeting of the SARS-CoV E protein will lead to a better understanding of its role in the assembly and release of virions.",,"['Cohen, Jennifer R.', 'Lin, Lisa D.', 'Machamer, Carolyn E.']",,,,
,PMC,Development and RNA-Synthesizing Activity of Coronavirus Replication Structures in the Absence of Protein Synthesis,http://dx.doi.org/10.1128/JVI.00403-11,PMC3094996,,,"The RNA replication and transcription complex of coronaviruses is associated with an elaborate reticulovesicular network (RVN) of modified endoplasmic reticulum. Using cycloheximide and puromycin, we have studied the effect of translation inhibition on the RNA synthesis of severe acute respiratory syndrome coronavirus and mouse hepatitis virus. Both inhibitors prevented the usual exponential increase in viral RNA synthesis, with immunofluorescence and electron microscopy indicating that RVN development came to a standstill. Nevertheless, limited RNA synthesis was supported, implying that continued translation is not an absolute requirement and suggesting a direct link between RVN formation and accumulation of coronavirus proteins.",,"['van den Worm, Sjoerd H. E.', 'Knoops, Kèvin', 'Zevenhoven-Dobbe, Jessika C.', 'Beugeling, Corrine', 'van der Meer, Yvonne', 'Mommaas, A. Mieke', 'Snijder, Eric J.']",,,,
,PMC,A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses,http://dx.doi.org/10.1128/JVI.02274-10,PMC3094985,,,"How viruses evolve to select their receptor proteins for host cell entry is puzzling. We recently determined the crystal structures of NL63 coronavirus (NL63-CoV) and SARS coronavirus (SARS-CoV) receptor-binding domains (RBDs), each complexed with their common receptor, human angiotensin-converting enzyme 2 (hACE2), and proposed the existence of a virus-binding hot spot on hACE2. Here we investigated the function of this hypothetical hot spot using structure-guided biochemical and functional assays. The hot spot consists of a salt bridge surrounded by hydrophobic tunnel walls. Mutations that disturb the hot spot structure have significant effects on virus/receptor interactions, revealing critical energy contributions from the hot spot structure. The tunnel structure at the NL63-CoV/hACE2 interface is more compact than that at the SARS-CoV/hACE2 interface, and hence RBD/hACE2 binding affinities are decreased either by NL63-CoV mutations decreasing the tunnel space or by SARS-CoV mutations increasing the tunnel space. Furthermore, NL63-CoV RBD inhibits hACE2-dependent transduction by SARS-CoV spike protein, a successful application of the hot spot theory that has the potential to become a new antiviral strategy against SARS-CoV infections. These results suggest that the structural features of the hot spot on hACE2 were among the driving forces for the convergent evolution of NL63-CoV and SARS-CoV.",,"['Wu, Kailang', 'Chen, Lang', 'Peng, Guiqing', 'Zhou, Wenbo', 'Pennell, Christopher A.', 'Mansky, Louis M.', 'Geraghty, Robert J.', 'Li, Fang']",,,,
,PMC,An Optimal cis-Replication Stem-Loop IV in the 5′ Untranslated Region of the Mouse Coronavirus Genome Extends 16 Nucleotides into Open Reading Frame 1,http://dx.doi.org/10.1128/JVI.00263-11,PMC3094970,,,"The 288-nucleotide (nt) 3′ untranslated region (UTR) in the genome of the bovine coronavirus (BCoV) and 339-nt 3′ UTR in the severe acute respiratory syndrome (SARS) coronavirus (SCoV) can each replace the 301-nt 3′ UTR in the mouse hepatitis coronavirus (MHV) for virus replication, thus demonstrating common 3′ cis-replication signals. Here, we show that replacing the 209-nt MHV 5′ UTR with the ∼63%-sequence-identical 210-nt BCoV 5′ UTR by reverse genetics does not yield viable virus, suggesting 5′ end signals are more stringent or possibly are not strictly 5′ UTR confined. To identify potential smaller, 5′-common signals, each of three stem-loop (SL) signaling domains and one inter-stem-loop domain from the BCoV 5′ UTR was tested by replacing its counterpart in the MHV genome. The SLI/II domain (nucleotides 1 to 84) and SLIII domain (nucleotides 85 to 141) each immediately enabled near-wild-type (wt) MHV-like progeny, thus behaving similarly to comparable 5′-proximal regions of the SCoV 5′ UTR as shown by others. The inter-stem-loop domain (nt 142 to 173 between SLs III and IV) enabled small plaques only after genetic adaptation. The SLIV domain (nt 174 to 210) required a 16-nt extension into BCoV open reading frame 1 (ORF1) for apparent stabilization of a longer BCoV SLIV (nt 174 to 226) and optimal virus replication. Surprisingly, pleiomorphic SLIV structures, including a terminal loop deletion, were found among debilitated progeny from intra-SLIV chimeras. The results show the inter-stem-loop domain to be a potential novel species-specific cis-replication element and that cis-acting SLIV in the viral genome extends into ORF1 in a manner that stabilizes its lower stem and is thus not 5′ UTR confined.",,"['Guan, Bo-Jhih', 'Wu, Hung-Yi', 'Brian, David A.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00697-11,PMC3094959,,,,,,,,,
,PMC,A New Ebola Virus Nonstructural Glycoprotein Expressed through RNA Editing,http://dx.doi.org/10.1128/JVI.02190-10,PMC3094950,,,"Ebola virus (EBOV), an enveloped, single-stranded, negative-sense RNA virus, causes severe hemorrhagic fever in humans and nonhuman primates. The EBOV glycoprotein (GP) gene encodes the nonstructural soluble glycoprotein (sGP) but also produces the transmembrane glycoprotein (GP(1,2)) through transcriptional editing. A third GP gene product, a small soluble glycoprotein (ssGP), has long been postulated to be produced also as a result of transcriptional editing. To identify and characterize the expression of this new EBOV protein, we first analyzed the relative ratio of GP gene-derived transcripts produced during infection in vitro (in Vero E6 cells or Huh7 cells) and in vivo (in mice). The average percentages of transcripts encoding sGP, GP(1,2), and ssGP were approximately 70, 25, and 5%, respectively, indicating that ssGP transcripts are indeed produced via transcriptional editing. N-terminal sequence similarity with sGP, the absence of distinguishing antibodies, and the abundance of sGP made it difficult to identify ssGP through conventional methodology. Optimized 2-dimensional (2D) gel electrophoresis analyses finally verified the expression and secretion of ssGP in tissue culture during EBOV infection. Biochemical analysis of recombinant ssGP characterized this protein as a disulfide-linked homodimer that was exclusively N glycosylated. In conclusion, we have identified and characterized a new EBOV nonstructural glycoprotein, which is expressed as a result of transcriptional editing of the GP gene. While ssGP appears to share similar structural properties with sGP, it does not appear to have the same anti-inflammatory function on endothelial cells as sGP.",,"['Mehedi, Masfique', 'Falzarano, Darryl', 'Seebach, Jochen', 'Hu, Xiaojie', 'Carpenter, Michael S.', 'Schnittler, Hans-Joachim', 'Feldmann, Heinz']",,,,
,PMC,Stem Cells and Cell Therapies in Lung Biology and Lung Diseases,http://dx.doi.org/10.1513/pats.201012-071DW,PMC3132784,,,,,"['Weiss, Daniel J.', 'Bertoncello, Ivan', 'Borok, Zea', 'Kim, Carla', 'Panoskaltsis-Mortari, Angela', 'Reynolds, Susan', 'Rojas, Mauricio', 'Stripp, Barry', 'Warburton, David', 'Prockop, Darwin J.']",,,,
,PMC,Lipopolysaccharide Inhibits Sindbis Virus-Induced IP-10 Release in Human Peripheral Blood Mononuclear Cells,http://dx.doi.org/10.1089/vim.2010.0120,PMC3109079,,,"Chemokines play a pivotal role in the innate response to both bacterial and viral infections, and in mixed infections. To determine chemokine responses to Sindbis virus (SIN) in a co-infection model, peripheral blood mononuclear cells (PBMCs) derived from healthy volunteers were exposed to SIN in the presence and absence of lipopolysaccharide (LPS). Culture supernatants recovered at 2, 24, and 72 h post-exposure were evaluated for virus replication and analyzed for chemokines by ELISA. None of the PBMC cultures showed new virus release, GFP reporter expression, or viral RNA synthesis. While SIN had little effect on the induction of IL-8 and RANTES, the chemokines MCP-1, MIP1-α (p < 0.001), and MIP1-β (p < 0.0004) were drastically upregulated by SIN as well as LPS. Both live and UV-inactivated SIN induced secretion of IP-10 and I-TAC. Although LPS did not induce release of IP-10, it sharply inhibited (p = 0.004) SIN-mediated IP-10 secretion. On the contrary, the release of SLC was blocked by SIN. The adjuvant activity of IP-10, its antiangiogenic function, and antagonism between SIN and LPS for the release of select chemokines may be useful in understanding the pathogenesis of mixed infections, cross-talk between cellular pathways, and may have applications in cancer and sepsis.",,"['Dhanushkodi, Nisha R.', 'Mohankumar, Vidyarani', 'Pokkali, Supriya', 'Raju, Ramaswamy']",,,,
,PMC,Risk factors for delays between intake and veterinary approval for adoption on medical grounds in shelter puppies and kittens,http://dx.doi.org/10.1016/j.prevetmed.2011.04.016,PMC3128297,,,"To maximize their capacity to save lives and optimize resource allocation, animal shelters need to identify highly adoptable animals that are unlikely to be delayed on medical grounds before they can be made available for adoption. In this retrospective cohort study, our objective was to identify risk factors for delays from intake to approval for adoption on medical grounds in shelter puppies and kittens. Shelter medical records from 2008 for 335 puppies and 370 kittens were selected randomly at a large metropolitan adoption-guarantee shelter. Data including signalment, source shelter, intake veterinary examination findings, clinical history and days from intake until approval by a veterinarian for adoption on medical grounds were extracted from shelter records and analyzed using multivariate Cox regression. Puppies and kittens with clinical signs of respiratory or gastrointestinal disease at intake took significantly longer to receive approval for adoption on medical grounds (puppies - respiratory p<0.0001; gastrointestinal p<0.0001; kittens - respiratory p<0.0001; gastrointestinal p=0.002). Stray kittens were more likely to be delayed than owner-relinquished kittens or those transferred from other shelters (p<0.01). Older kittens were less likely to be delayed (p<0.0001). Administration of oral or parenteral antibiotics to puppies and kittens with respiratory and/or ocular signs within 24 hours of intake significantly reduced time to approval on medical grounds for adoption (puppies p=0.02; kittens p=0.03). The analyses suggested that puppies and kittens with respiratory or gastrointestinal signs on intake are more likely to experience delays between intake and veterinary approval for adoption on medical grounds. Prompt antimicrobial treatment of animals with respiratory and/or ocular signs may decrease length of stay in the shelter.",,"['Litster, Annette', 'Allen, Joselyn', 'Mohamed, Ahmed', 'He, Shuang']",,,,
,PMC,Immune signaling by RIG-I-like receptors,http://dx.doi.org/10.1016/j.immuni.2011.05.003,PMC3177755,,,"The RIG-I-like receptors (RLRs) RIG-I, MDA5, and LGP2 play a major role in pathogen sensing of RNA virus infection to initiate and modulate antiviral immunity. The RLRs detect viral RNA ligands or processed self RNA in the cytoplasm to triggers innate immunity and inflammation and to impart gene expression that serves to control infection. Importantly, RLRs cooperate in signaling crosstalk networks with Toll-like receptors and other factors to impart innate immunity and to modulate the adaptive immune response. RLR regulation occurs at a variety of levels ranging from autoregulation to ligand and co-factor interactions and post-translational modifications. Abberant RLR signaling or dysregulation of RLR expression is now implicated in the development of autoimmune diseases. Understanding the processes of RLR signaling and response will provide insights to guide RLR-targeted therapeutics for antiviral and immune modifying applications.",,"['Loo, Yueh-Ming', 'Gale, Michael']",,,,
,PMC,MicroRNAs and human retroviruses,http://dx.doi.org/10.1016/j.bbagrm.2011.05.009,PMC3177989,,,"MicroRNAs (miRNAs) are small non-coding RNAs that control a multitude of critical processes in mammalian cells. Increasing evidence has emerged that host miRNAs serve in animal cells to restrict viral infections. In turn, many viruses encode RNA silencing suppressors (RSS) which are employed to moderate the potency of the cell’s miRNA selection against viral replication. Some viruses also encode viral miRNAs. In this review, we summarize findings from human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1) that illustrate examples of host cell miRNAs that target the viruses, of RSS encoded by viruses, and of host cell miRNA profile changes that are seen in infected cells.",,"['Houzet, Laurent', 'Jeang, Kuan-Teh']",,,,
,PMC,A novel methodology for large-scale phylogeny partition,http://dx.doi.org/10.1038/ncomms1325,PMC6045912,,,"Understanding the determinants of virus transmission is a fundamental step for effective design of screening and intervention strategies to control viral epidemics. Phylogenetic analysis can be a valid approach for the identification of transmission chains, and very-large data sets can be analysed through parallel computation. Here we propose and validate a new methodology for the partition of large-scale phylogenies and the inference of transmission clusters. This approach, on the basis of a depth-first search algorithm, conjugates the evaluation of node reliability, tree topology and patristic distance analysis. The method has been applied to identify transmission clusters of a phylogeny of 11,541 human immunodeficiency virus-1 subtype B pol gene sequences from a large Italian cohort. Molecular transmission chains were characterized by means of different clinical/demographic factors, such as the interaction between male homosexuals and male heterosexuals. Our method takes an advantage of a flexible notion of transmission cluster and can become a general framework to analyse other epidemics.",,"['Prosperi, Mattia C.F.', 'Ciccozzi, Massimo', 'Fanti, luri', 'Saladini, Francesco', 'Pecorari, Monica', 'Borghi, Vanni', 'Di Giambenedetto, Simona', 'Bruzzone, Bianca', 'Capetti, Amedeo', 'Vivarelli, Angela', 'Rusconi, Stefano', 'Carla Re, Maria', 'Gismondo, Maria Rita', 'Sighinolfi, Laura', 'Gray, Rebecca R.', 'Salemi, Marco', 'Zazzi, Maurizio', 'De Luca, Andrea']",,,,
,PMC,"Inhibitors of SARS-3CL(pro): Virtual Screening, Biological Evaluation and Molecular Dynamics Simulation Studies",http://dx.doi.org/10.1021/ci1004916,PMC3929308,,,"SARS-CoV from the coronaviridae family has been identified as the etiological agent of Severe Acute Respiratory Syndrome (SARS), a highly contagious upper respiratory disease that reached epidemic status in 2002. SARS-3CL(pro), a cysteine protease indispensible to the viral life cycle, has been identified as one of the key therapeutic target against SARS. A combined ligand and structure based virtual screening was carried out against the Asinex Platinum collection. Multiple low micromolar inhibitors of the enzyme were identified through this search, one of which also showed activity against SARS-CoV in a whole cell CPE assay. Furthermore, multi nanosecond explicit solvent simulations were carried out using the docking poses of the identified hits to study the overall stability of the binding site interactions as well as identify important changes in the interaction profile that were not apparent from the docking study. Cumulative analysis of the evaluated compounds and the simulation studies led to the identification of certain protein-ligand interaction patterns which would be useful in further structure based design efforts.",,"['Mukherjee, Prasenjit', 'Shah, Falgun', 'Desai, Prashant', 'Avery, Mitchell']",,,,
,PMC,A host-restricted viral vector for antigen-specific immunization against Lyme disease pathogen,http://dx.doi.org/10.1016/j.vaccine.2011.05.010,PMC3138909,,,"Newcastle disease virus (NDV) is an avian virus that is attenuated in primates and is a potential vaccine vector for human use. We evaluated NDV as a vector for expressing selected antigens of the Lyme disease pathogen Borrelia burgdorferi. A series of recombinant NDVs were generated that expressed intracellular or extracellular forms of two Borrelia burgdorferi antigens: namely, the basic membrane protein A (BmpA) and the outer surface protein C (OspC). Expression of the intracellular and extracellular forms of these antigens was confirmed in cultured chicken cells. C3H or Balb/C mice that were immunized intranasally with the NDV vectors mounted vigorous serum antibody responses against the NDV vector, but failed to mount a robust response against either the intracellular or extracellular forms of BmpA or OspC. In contrast, a single immunization of hamsters with the NDV vectors via the intranasal, intramuscular, or intraperitoneal route resulted in rapid and rigorous antibody responses against the intracellular or extracellular forms of BmpA and OspC. When groups of hamsters were separately inoculated with various NDV vectors and challenged with B. burgdorferi (10(8) cells/animal), immunization with vector expressing either intracellular or extracellular BmpA was associated with a significant reduction of the pathogen load in the joints. Taken together, our studies highlighted the importance of NDV as vaccine vector that can be used for simple yet effective immunization of hosts against bacterial infections including Lyme disease.",,"['Xiao, Sa', 'Kumar, Manish', 'Yang, Xiuli', 'Akkoyunlu, Mustafa', 'Collins, Peter L.', 'Samal, Siba K.', 'Pal, Utpal']",,,,
,PMC,Structural and Biochemical Studies on the Regulation of Biotin Carboxylase by Substrate Inhibition and Dimerization,http://dx.doi.org/10.1074/jbc.M111.220517,PMC3129220,,,"Biotin carboxylase (BC) activity is shared among biotin-dependent carboxylases and catalyzes the Mg-ATP-dependent carboxylation of biotin using bicarbonate as the CO(2) donor. BC has been studied extensively over the years by structural, kinetic, and mutagenesis analyses. Here we report three new crystal structures of Escherichia coli BC at up to 1.9 Å resolution, complexed with different ligands. Two structures are wild-type BC in complex with two ADP molecules and two Ca(2+) ions or two ADP molecules and one Mg(2+) ion. One ADP molecule is in the position normally taken by the ATP substrate, whereas the other ADP molecule occupies the binding sites of bicarbonate and biotin. One Ca(2+) ion and the Mg(2+) ion are associated with the ADP molecule in the active site, and the other Ca(2+) ion is coordinated by Glu-87, Glu-288, and Asn-290. Our kinetic studies confirm that ATP shows substrate inhibition and that this inhibition is competitive against bicarbonate. The third structure is on the R16E mutant in complex with bicarbonate and Mg-ADP. Arg-16 is located near the dimer interface. The R16E mutant has only a 2-fold loss in catalytic activity compared with the wild-type enzyme. Analytical ultracentrifugation experiments showed that the mutation significantly destabilized the dimer, although the presence of substrates can induce dimer formation. The binding modes of bicarbonate and Mg-ADP are essentially the same as those to the wild-type enzyme. However, the mutation greatly disrupted the dimer interface and caused a large re-organization of the dimer. The structures of these new complexes have implications for the catalysis by BC.",,"['Chou, Chi-Yuan', 'Tong, Liang']",,,,
,PMC,Probing the HIV gp120 Envelope Glycoprotein Conformation by NMR,http://dx.doi.org/10.1074/jbc.M111.251025,PMC3129179,,,"The HIV envelope glycoprotein gp120 plays a critical role in virus entry, and thus, its structure is of extreme interest for the development of novel therapeutics and vaccines. To date, high resolution structural information about gp120 in complex with gp41 has proven intractable. In this study, we characterize the structural properties of gp120 in the presence and absence of gp41 domains by NMR. Using the peptide probe 12p1 (sequence, RINNIPWSEAMM), which was identified previously as an entry inhibitor that binds to gp120, we identify atoms of 12p1 in close contact with gp120 in the monomeric and trimeric states. Interestingly, the binding mode of 12p1 with gp120 is similar for clades B and C. In addition, we show a subtle difference in the binding mode of 12p1 in the presence of gp41 domains, i.e. the trimeric state, which we interpret as small differences in the gp120 structure in the presence of gp41.",,"['Celigoy, Jessica', 'Ramirez, Benjamin', 'Tao, Lin', 'Rong, Lijun', 'Yan, Lianying', 'Feng, Yan-Ru', 'Quinnan, Gerald V.', 'Broder, Christopher C.', 'Caffrey, Michael']",,,,
,PMC,"Arf Family G Proteins and their regulators: roles in membrane transport, development and disease",http://dx.doi.org/10.1038/nrm3117,PMC3245550,,,,,"['Donaldson, Julie G.', 'Jackson, Catherine L.']",,,,
,PMC,Thermoregulation and Thermography in Neonatal Physiology and Disease,http://dx.doi.org/10.1177/1099800411403467,PMC3775585,,,,,"['Knobel, Robin B.', 'Guenther, Bob D.', 'Rice, Henry E.']",,,,
,PMC,Current drivers and future directions of global livestock disease dynamics,http://dx.doi.org/10.1073/pnas.1012953108,PMC3876220,,,"We review the global dynamics of livestock disease over the last two decades. Our imperfect ability to detect and report disease hinders assessment of trends, but we suggest that, although endemic diseases continue their historic decline in wealthy countries, poor countries experience static or deteriorating animal health and epidemic diseases show both regression and expansion. At a mesolevel, disease is changing in terms of space and host, which is illustrated by bluetongue, Lyme disease, and West Nile virus, and it is also emerging, as illustrated by highly pathogenic avian influenza and others. Major proximate drivers of change in disease dynamics include ecosystem change, ecosystem incursion, and movements of people and animals; underlying these are demographic change and an increasing demand for livestock products. We identify three trajectories of global disease dynamics: (i) the worried well in developed countries (demanding less risk while broadening the circle of moral concern), (ii) the intensifying and market-orientated systems of many developing countries, where highly complex disease patterns create hot spots for disease shifts, and (iii) the neglected cold spots in poor countries, where rapid change in disease dynamics is less likely but smallholders and pastoralists continue to struggle with largely preventable and curable livestock diseases.",,"['Perry, Brian D.', 'Grace, Delia', 'Sones, Keith']",,,,
,PMC,Molecular Imaging of Influenza and Other Emerging Respiratory Viral Infections,http://dx.doi.org/10.1093/infdis/jir038,PMC3080905,,,"Research on the pathogenesis and therapy of influenza and other emerging respiratory viral infections would be aided by methods that directly visualize pathophysiologic processes in patients and laboratory animals. At present, imaging of diseases, such as swine-origin H1N1 influenza, is largely restricted to chest radiograph and computed tomography (CT), which can detect pulmonary structural changes in severely ill patients but are more limited in characterizing the early stages of illness, differentiating inflammation from infection or tracking immune responses. In contrast, imaging modalities, such as positron emission tomography, single photon emission CT, magnetic resonance imaging, and bioluminescence imaging, which have become useful tools for investigating the pathogenesis of a range of disease processes, could be used to advance in vivo studies of respiratory viral infections in patients and animals. Molecular techniques might also be used to identify novel biomarkers of disease progression and to evaluate new therapies.",,"['Bray, Mike', 'Lawler, James', 'Paragas, Jason', 'Jahrling, Peter B.', 'Mollura, Daniel J.']",,,,
,PMC,Converging towards the optimal path to extinction,http://dx.doi.org/10.1098/rsif.2011.0159,PMC3203485,,,"Extinction appears ubiquitously in many fields, including chemical reactions, population biology, evolution and epidemiology. Even though extinction as a random process is a rare event, its occurrence is observed in large finite populations. Extinction occurs when fluctuations owing to random transitions act as an effective force that drives one or more components or species to vanish. Although there are many random paths to an extinct state, there is an optimal path that maximizes the probability to extinction. In this paper, we show that the optimal path is associated with the dynamical systems idea of having maximum sensitive dependence to initial conditions. Using the equivalence between the sensitive dependence and the path to extinction, we show that the dynamical systems picture of extinction evolves naturally towards the optimal path in several stochastic models of epidemics.",,"['Schwartz, Ira B.', 'Forgoston, Eric', 'Bianco, Simone', 'Shaw, Leah B.']",,,,
,PMC,Human Mitochondrial RNA Polymerase: Evaluation of the Single-Nucleotide-Addition Cycle on Synthetic RNA/DNA Scaffolds,http://dx.doi.org/10.1021/bi200350d,PMC3698222,,,"The human mitochondrial RNA polymerase (h-mtRNAP) serves as both the transcriptase for expression and the primase for replication of mitochondrial DNA. As such, the enzyme is of fundamental importance to cellular energy metabolism, and defects in its function may be related to human disease states. Here we describe in vitro analysis of the h-mtRNAP kinetic mechanism for single, correct nucleotide incorporation. This was made possible by the development of efficient methods for expression and purification of h-mtRNAP using a bacterial system and by utilization of assays that rely on simple, synthetic RNA/DNA scaffolds without the need for mitochondrial transcription accessory proteins. We find that h-mtRNAP accomplishes single-nucleotide incorporation by using the same core steps, including conformational change steps before and after chemistry, that are prototypical for most types of nucleic acid polymerases. The polymerase binds to scaffolds via a two-step mechanism consisting of a fast initial-encounter step followed by a much slower isomerization that leads to catalytic competence. A substantial solvent deuterium kinetic isotope effect was observed for the forward reaction, but none was detectable for the reverse reaction, suggesting that chemistry is at least partially rate-limiting in the forward direction but not in the reverse. h-mtRNAP appears to exercise much more stringent surveillance over base than over sugar in determining the correctness of a nucleotide. The utility of developing the robust in vitro assays described here and of establishing a baseline of kinetic performance for the wild-type enzyme is that biological questions concerning h-mtRNAP may now begin to be addressed. [Image: see text]",,"['Smidansky, Eric D.', 'Arnold, Jamie J.', 'Reynolds, Shelley L.', 'Cameron, Craig E.']",,,,
,PMC,The Effect of Steroid Use in Hospitalized Adults With Respiratory Syncytial Virus-Related Illness,http://dx.doi.org/10.1378/chest.11-0047,PMC3205848,,,"RATIONALE: Systemic glucocorticosteroids (steroids) are commonly prescribed for patients with exacerbations of COPD during acute viral infections such as respiratory syncytial virus (RSV). The effects of short-term high-dose steroid treatment on viral load and adaptive immunity to RSV have not been examined in adults. OBJECTIVES: The objectives of this study were to measure peak viral load and duration of viral shedding, serum and nasal cytokines, RSV-specific antibody response, and lymphocyte subsets in patients admitted to the hospital with RSV infection and to compare patients treated with steroids to patients untreated with steroids. METHODS: Hospitalized adults who tested positive for RSV by reverse transcription-polymerase chain reaction (RT-PCR) on admission had respiratory samples collected for quantitative RT-PCR and cytokine analysis. Serum and nasal secretions were tested for RSV antibody and lymphocyte subsets were analyzed by flow cytometry at 2 days, 2 weeks, and 1 month. MAIN RESULTS: Thirty-three of 50 (66%) patients hospitalized with RSV received systemic steroids for a mean duration of 11 days. Those who received steroids more frequently wheezed and were less often febrile. There were no serious adverse events related to steroids and no significant differences in peak viral load, duration of RSV shedding, nasal cytokines, or lymphocyte subsets in patients treated with steroids and patients untreated with steroids. Antibody responses to RSV were slightly blunted in the steroid-treated group. CONCLUSIONS: Short courses of systemic steroids in patients hospitalized with RSV infection did not affect viral load or shedding. Humoral immunity may be mildly diminished, and thus potential benefits of systemic steroids must be balanced against potential risks.",,"['Lee, F. Eun-Hyung', 'Walsh, Edward E.', 'Falsey, Ann R.']",,,,
,PMC,RETROCYCLINS AND THEIR ACTIVITY AGAINST HIV-1,http://dx.doi.org/10.1007/s00018-011-0715-5,PMC4511374,,,"Primate theta-defensins are physically distinguished as the only known fully-cyclic peptides of animal origin. Humans do not produce theta-defensin peptides due to a premature stop codon present in the signal sequence of all six theta-defensin pseudogenes. Instead, since the putative coding regions of human theta-defensin pseudogenes have remained remarkably intact, their corresponding peptides, called “retrocyclins”, have been recreated using solid-phase synthetic approaches. Retrocyclins exhibit an exceptional therapeutic index both as inhibitors of HIV-1 entry and as bactericidal agents, which makes retrocyclins promising candidates for further development as topical microbicides to prevent sexually transmitted diseases. This review presents the evolution, antiretroviral mechanism of action, and potential clinical applications of retrocyclins to prevent sexual transmission of HIV-1.",,"['Penberthy, W. Todd', 'Chari, Soumya', 'Cole, Amy L.', 'Cole, Alexander M.']",,,,
,PMC,Molecular dynamics simulations of viral RNA polymerases link conserved and correlated motions of functional elements to fidelity,http://dx.doi.org/10.1016/j.jmb.2011.04.078,PMC3114172,,,"The viral RNA-dependent RNA polymerase (RdRp) is essential for multiplication of all RNA viruses. The sequence diversity of an RNA virus population contributes to its ability to infect the host. This diversity emanates from errors made by the RdRp during RNA synthesis. The physical basis for RdRp fidelity is unclear but is linked to conformational changes occurring during the nucleotide-addition cycle. To understand RdRp dynamics that might influence RdRp function, we have analyzed all-atom molecular dynamics (MD) simulations on the nanosecond timescale of four RdRps from the picornavirus family that exhibit 30–74% sequence identity. Principal component analysis showed that the major motions observed during the simulations derived from conserved structural motifs and regions of known function. Dynamics of residues participating in the same biochemical property, for example RNA binding, nucleotide binding or catalysis, were correlated even when spatially distant on the RdRp structure. The conserved and correlated dynamics of functional, structural elements suggest co-evolution of dynamics with structure and function of the RdRp. Crystal structures of all picornavirus RdRps exhibit a template-nascent RNA duplex channel too small to fully accommodate duplex RNA. Simulations revealed opening and closing motions of the RNA and NTP channels, which might be relevant to NTP entry, PP(i) exit and translocation. A role for nanosecond timescale dynamics in RdRp fidelity is supported by altered dynamics of the high-fidelity G64S derivative of PV RdRp relative to wild-type enzyme.",,"['Moustafa, Ibrahim M.', 'Shen, Hujun', 'Morton, Brandon', 'Colina, Coray M.', 'Cameron, Craig E.']",,,,
,PMC,Egg Yolk IgY: Protection against Rotavirus induced Diarrhea and Modulatory effect on the systemic and mucosal antibody responses in newborn calves,http://dx.doi.org/10.1016/j.vetimm.2011.05.003,PMC3155943,,,"Bovine rotavirus (BRV) is an important cause of diarrhea in newborn calves. Local passive immunity is the most efficient protective strategy to control the disease. IgY technology (the use of chicken egg yolk immunoglobulins) is an economic and practical alternative to prevent BRV diarrhea in dairy calves. The aim of this study was to evaluate the protection and immunomodulation induced by the oral administration of egg yolk enriched in BRV specific IgY to experimentally BRV infected calves. All calves in groups Gp 1, 2 and 3 received control colostrum (CC; BRV virus neutralization Ab titer – VN- =65,536; ELISA BRV IgG(1) =16,384) prior to gut closure. After gut closure, calves received milk supplemented with 6% BRV-immune egg yolk [(Gp1) VN=2048; ELISA IgY Ab titer =4096] or non-immune control egg yolk [(Gp2) VN <4; ELISA IgY Ab titer <4) twice a day, for 14 days. Calves receiving CC only or colostrum deprived calves (CD) fed antibody (Ab) free milk served as controls (Gp 3 and 4, respectively). Calves were inoculated with 10(5.85) focus forming units (FFU) of virulent BRV IND at 2 days of age. Control calves (Gp 3 and 4) and calves fed control IgY (Gp 2) were infected and developed severe diarrhea. Around 80% calves in Gp 1 (IgY 4096) were infected, but they showed 80% (4/5) protection against BRV diarrhea. Bovine RV-specific IgY Ab were detected in the feces of calves in Gp 1, indicating that avian antibodies (Abs) remained intact after passage through the gastrointestinal tract. At post infection day 21, the duodenum was the major site of BRV specific antibody secreting cells (ASC) in all experimental groups. Mucosal ASC responses of all isotypes were significantly higher in the IgY treated groups, independently of the specificity of the treatment, indicating that egg yolk components modulated the immune response against BRV infection at the mucosal level. These results indicate that supplementing newborn calves’ diets for the first 14 days of life with egg yolk enriched in BRV-specific IgY represents a promising strategy to prevent BRV diarrhea. Moreover a strong active ASC immune response is induced in the intestinal mucosa following BRV infection after the administration of egg yolk, regardless the specificity of the treatment.",,"['Vega, C.', 'Bok, M.', 'Chacana, P.', 'Saif, L.', 'Fernandez, F.', 'Parreño, V.']",,,,
,PMC,Tyrosine kinase receptor Axl enhances entry of Zaire ebolavirus without direct interactions with the viral glycoprotein,http://dx.doi.org/10.1016/j.virol.2011.04.002,PMC3107944,,,"In a bioinformatics-based screen for cellular genes that enhance Zaire ebolavirus (ZEBOV) transduction, AXL mRNA expression strongly correlated with ZEBOV infection. A series of cell lines and primary cells were identified that require Axl for optimal ZEBOV entry. Using one of these cell lines, we identified ZEBOV entry events that are Axl-dependent. Interactions between ZEBOV-GP and the Axl ectodomain were not detected in immunoprecipitations and reduction of surface expressed Axl by RNAi did not alter ZEBOV-GP binding, providing evidence that Axl does not serve as a receptor for the virus. However, RNAi knock down of Axl reduced ZEBOV pseudovirion internalization and α-Axl antisera inhibited pseudovirion fusion with cellular membranes. Consistent with the importance of Axl for ZEBOV transduction, Axl transiently co-localized on the surface of cells with ZEBOV virus particles and was internalized during virion transduction. In total, these findings indicate that endosomal uptake of filoviruses is facilitated by Axl.",,"['Brindley, Melinda A.', 'Hunt, Catherine L.', 'Kondratowicz, Andrew S.', 'Bowman, Jill', 'Sinn, Patrick L.', 'McCray, Paul B.', 'Quinn, Kathrina', 'Weller, Melodie L.', 'Chiorini, John A.', 'Maury, Wendy']",,,,
,PMC,Aptamer in Bioanalytical Applications,http://dx.doi.org/10.1021/ac201057w,PMC3115435,,,,,"['Iliuk, Anton B.', 'Hu, Lianghai', 'Tao, W. Andy']",,,,
,PMC,Fine epitope mapping of monoclonal antibodies against hemagglutinin of a highly pathogenic H5N1 influenza virus using yeast surface display,http://dx.doi.org/10.1016/j.bbrc.2011.04.139,PMC3119598,,,"Highly pathogenic H5N1 avian influenza viruses pose a debilitating pandemic threat. Thus, understanding mechanisms of antibody-mediated viral inhibition and neutralization escape is critical. Here, a robust yeast display system for fine epitope mapping of viral surface hemagglutinin (HA)-specific antibodies is demonstrated. The full-length H5 subtype HA (HA0) was expressed on the yeast surface in a correctly folded conformation, determined by binding of a panel of extensively characterized neutralizing human monoclonal antibodies (mAbs). These mAbs target conformationally-dependent epitopes of influenza A HA, which are highly conserved across H5 clades and group 1 serotypes. By separately displaying HA1 and HA2 subunits on yeast, domain mapping of two anti-H5 mAbs, NR2728 and H5-2A, localized their epitopes to HA1. These anti-H5 mAb epitopes were further fine mapped by using a library of yeast-displayed HA1 mutants and selecting for loss of binding without prior knowledge of potential contact residues. By overlaying key mutant residues that impacted binding onto a crystal structure of HA, the NR2728 mAb was found to interact with a fully surface-exposed contiguous patch of residues at the receptor binding site (RBS), giving insight into the mechanism underlying its potent inhibition of virus binding. The non-neutralizing H5-2A mAb was similarly mapped to a highly conserved H5 strain-specific but poorly accessible location on a loop at the trimer HA interface. These data further augment our toolchest for studying HA antigenicity, epitope diversity and accessibility in response to natural and experimental influenza infection and vaccines.",,"['Han, Thomas', 'Sui, Jianhua', 'Bennett, Andrew S.', 'Liddington, Robert C.', 'Donis, Ruben O.', 'Zhu, Quan', 'Marasco, Wayne A.']",,,,
,PMC,Role of p38 Protein Kinase in the Ligand-independent Ubiquitination and Down-regulation of the IFNAR1 Chain of Type I Interferon Receptor,http://dx.doi.org/10.1074/jbc.M111.238766,PMC3121351,,,"Phosphorylation-dependent ubiquitination and degradation of the IFNAR1 chain of type I interferon (IFN) receptor is a robust and specific mechanism that limits the magnitude and duration of IFNα/β signaling. Besides the ligand-inducible IFNAR1 degradation, the existence of an “inside-out” signaling that accelerates IFNAR1 turnover in the cells undergoing the endoplasmic reticulum (ER) stress and activated unfolded protein responses has been recently described. The latter pathway does not require either presence of ligands (IFNα/β) or catalytic activity of Janus kinases (JAK). Instead, this pathway relies on activation of the PKR-like ER kinase (PERK) and ensuing specific priming phosphorylation of IFNAR1. Here, we describe studies that identify the stress activated p38 protein kinase as an important regulator of IFNAR1 that acts downstream of PERK. Results of the experiments using pharmacologic p38 kinase inhibitors, RNA interference approach, and cells from p38α knock-out mice suggest that p38 kinase activity is required for priming phosphorylation of IFNAR1 in cells undergoing unfolded protein response. We further demonstrate an important role of p38 kinase in the ligand-independent stimulation of IFNAR1 ubiquitination and degradation and ensuing attenuation of IFNα/β signaling and anti-viral defenses. We discuss the distinct importance of p38 kinase in regulating the overall responses to type I IFN in cells that have been already exposed to IFNα/β versus those cells that are yet to encounter these cytokines.",,"['Bhattacharya, Sabyasachi', 'Qian, Juan', 'Tzimas, Christos', 'Baker, Darren P.', 'Koumenis, Constantinos', 'Diehl, J. Alan', 'Fuchs, Serge Y.']",,,,
,PMC,"Protocol for Recombinant RBD-based SARS Vaccines: Protein Preparation, Animal Vaccination and Neutralization Detection",http://dx.doi.org/10.3791/2444,PMC3197098,,,"Based on their safety profile and ability to induce potent immune responses against infections, subunit vaccines have been used as candidates for a wide variety of pathogens (1-3). Since the mammalian cell system is capable of post-translational modification, thus forming properly folded and glycosylated proteins, recombinant proteins expressed in mammalian cells have shown the greatest potential to maintain high antigenicity and immunogenicity (4-6). Although no new cases of SARS have been reported since 2004, future outbreaks are a constant threat; therefore, the development of vaccines against SARS-CoV is a prudent preventive step and should be carried out. The RBD of SARS-CoV S protein plays important roles in receptor binding and induction of specific neutralizing antibodies against virus infection (7-9). Therefore, in this protocol, we describe novel methods for developing a RBD-based subunit vaccine against SARS. Briefly, the recombinant RBD protein (rRBD) was expressed in culture supernatant of mammalian 293T cells to obtain a correctly folded protein with proper conformation and high immunogenicity (6). The transfection of the recombinant plasmid encoding RBD to the cells was then performed using a calcium phosphate transfection method (6,10) with some modifications. Compared with the lipid transfection method (11,12), this modified calcium phosphate transfection method is cheaper, easier to handle, and has the potential to reach high efficacy once a transfection complex with suitable size and shape is formed (13,14). Finally, a SARS pseudovirus neutralization assay was introduced in the protocol and used to detect the neutralizing activity of sera of mice vaccinated with rRBD protein. This assay is relatively safe, does not involve an infectious SARS-CoV, and can be performed without the requirement of a biosafety-3 laboratory (15). The protocol described here can also be used to design and study recombinant subunit vaccines against other viruses with class I fusion proteins, for example, HIV, respiratory syncytial virus (RSV), Ebola virus, influenza virus, as well as Nipah and Handra viruses. In addition, the methods for generating a pseudovirus and subsequently establishing a pseudovirus neutralization assay can be applied to all these viruses.",,"['Du, Lanying', 'Zhang, Xiujuan', 'Liu, Jixiang', 'Jiang, Shibo']",,,,
,PMC,T-cell immunoglobulin and mucin domain 1 (TIM-1) is a receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus,http://dx.doi.org/10.1073/pnas.1019030108,PMC3100998,,,"The glycoproteins (GP) of enveloped viruses facilitate entry into the host cell by interacting with specific cellular receptors. Despite extensive study, a cellular receptor for the deadly filoviruses Ebolavirus and Marburgvirus has yet to be identified and characterized. Here, we show that T-cell Ig and mucin domain 1 (TIM-1) binds to the receptor binding domain of the Zaire Ebola virus (EBOV) glycoprotein, and ectopic TIM-1 expression in poorly permissive cells enhances EBOV infection by 10- to 30-fold. Conversely, reduction of cell-surface expression of TIM-1 by RNAi decreased infection of highly permissive Vero cells. TIM-1 expression within the human body is broader than previously appreciated, with expression on mucosal epithelia from the trachea, cornea, and conjunctiva—tissues believed to be important during in vivo transmission of filoviruses. Recognition that TIM-1 serves as a receptor for filoviruses on these mucosal epithelial surfaces provides a mechanistic understanding of routes of entry into the human body via inhalation of aerosol particles or hand-to-eye contact. ARD5, a monoclonal antibody against the IgV domain of TIM-1, blocked EBOV binding and infection, suggesting that antibodies or small molecules directed against this cellular receptor may provide effective filovirus antivirals.",,"['Kondratowicz, Andrew S.', 'Lennemann, Nicholas J.', 'Sinn, Patrick L.', 'Davey, Robert A.', 'Hunt, Catherine L.', 'Moller-Tank, Sven', 'Meyerholz, David K.', 'Rennert, Paul', 'Mullins, Robert F.', 'Brindley, Melinda', 'Sandersfeld, Lindsay M.', 'Quinn, Kathrina', 'Weller, Melodie', 'McCray, Paul B.', 'Chiorini, John', 'Maury, Wendy']",,,,
,PMC,Global Oral Health Inequalities: The View from a Research Funder,http://dx.doi.org/10.1177/0022034511402015,PMC3144034,,,"Despite impressive worldwide improvements in oral health, inequalities in oral health status among and within countries remain a daunting public health challenge. Oral health inequalities arise from a complex web of health determinants, including social, behavioral, economic, genetic, environmental, and health system factors. Eliminating these inequalities cannot be accomplished in isolation of oral health from overall health, or without recognizing that oral health is influenced at multiple individual, family, community, and health systems levels. For several reasons, this is an opportune time for global efforts targeted at reducing oral health inequalities. Global health is increasingly viewed not just as a humanitarian obligation, but also as a vehicle for health diplomacy and part of the broader mission to reduce poverty, build stronger economies, and strengthen global security. Despite the global economic recession, there are trends that portend well for support of global health efforts: increased globalization of research and development, growing investment from private philanthropy, an absolute growth of spending in research and innovation, and an enhanced interest in global health among young people. More systematic and far-reaching efforts will be required to address oral health inequalities through the engagement of oral health funders and sponsors of research, with partners from multiple public and private sectors. The oral health community must be “at the table” with other health disciplines and create opportunities for eliminating inequalities through collaborations that can harness both the intellectual and financial resources of multiple sectors and institutions.",,"['Garcia, I.', 'Tabak, L.A.']",,,,
,PMC,Osteonecrosis in Children After Therapy for Malignancy,http://dx.doi.org/10.2214/AJR.10.6073,PMC4700933,,,"OBJECTIVE: Osteonecrosis in the growing population of childhood cancer survivors results from disease and treatment. Imagers must be knowledgeable about patient groups at risk for its development, patterns of involvement and potential implications. This review will focus on implications of this potentially life-altering toxicity. CONCLUSION: Childhood cancer survivors are at increased risk for developing osteonecrosis. Because osteonecrosis is often asymptomatic until late in the process, imaging is critical for its detection and characterization when interventions may be most effective to ameliorate its progression.",,"['Kaste, Sue C.', 'Karimova, Evguenia J.', 'Neel, Michael D.']",,,,
,PMC,Experimental induction of psychogenic illness in the context of a medical event and media exposure,,PMC3195398,,,"OBJECTIVES: Mass psychogenic illness can be a significant problem for triage and hospital surge in disasters; however, research has been largely limited to posthoc observational reports. Reports on the impact of public media during a disaster have suggested both salutary as well as iatrogenic psychological effects. This study was designed to determine if psychogenic illness can be evoked and if media will exacerbate it in a plausible, controlled experiment among healthy community adults. METHODS: A randomized controlled experiment used a simulated biological threat and elements of social contagion—essential precipitants of mass psychogenic illness. Participants were randomly assigned to one of three groups: no-intervention control group, psychogenic illness induction group, or psychogenic illness induction plus media group. Measures included three assessments of symptom intensity, heart rate, blood pressure, as well as questionnaires to measure potential psychogenic illness risk factors. RESULTS: The two psychogenic induction groups experienced 11 times more symptoms than the control group. Psychogenic illness was observed in both men and women at rates that were not significantly different. Higher rates of lifetime history of traumatic events and depression were associated with greater induction of illness. Media was not found to exacerbate symptom onset. CONCLUSIONS: Psychogenic illness relevant to public health disasters can be evoked in an experimental setting. This sets the stage for further research on psychogenic illness and strategies for mitigation.",,"['Broderick, Joan E.', 'Kaplan-Liss, Evonne', 'Bass, Elizabeth']",,,,
,PMC,Canadian Federal Support for Climate Change and Health Research Compared With the Risks Posed,http://dx.doi.org/10.2105/AJPH.2010.300105,PMC3076403,,,"For emerging public health risks such as climate change, the Canadian federal government has a mandate to provide information and resources to protect citizens' health. Research is a key component of this mandate and is essential if Canada is to moderate the health effects of a changing climate. We assessed whether federal support for climate change and health research is consistent with the risks posed. We audited projects receiving federal support between 1999 and 2009, representing an investment of Can$16 million in 105 projects. Although funding has increased in recent years, it remains inadequate, with negligible focus on vulnerable populations, limited research on adaptation, and volatility in funding allocations. A federal strategy to guide research support is overdue.",,"['Ford, James D.', 'Smith, Tanya R.', 'Berrang-Ford, Lea']",,,,
,PMC,An Official American Thoracic Society Research Statement: Noninfectious Lung Injury after Hematopoietic Stem Cell Transplantation: Idiopathic Pneumonia Syndrome,http://dx.doi.org/10.1164/rccm.2007-413ST,PMC3266140,,,"Rationale: Acute lung dysfunction of noninfectious etiology, known as idiopathic pneumonia syndrome (IPS), is a severe complication following hematopoietic stem cell transplantation (HSCT). Several mouse models have been recently developed to determine the underlying causes of IPS. A cohesive interpretation of experimental data and their relationship to the findings of clinical research studies in humans is needed to better understand the basis for current and future clinical trials for the prevention/treatment of IPS. Objectives: Our goal was to perform a comprehensive review of the preclinical (i.e., murine models) and clinical research on IPS. Methods: An ATS committee performed PubMed and OVID searches for published, peer-reviewed articles using the keywords “idiopathic pneumonia syndrome” or “lung injury” or “pulmonary complications” AND “bone marrow transplant” or “hematopoietic stem cell transplant.” No specific inclusion or exclusion criteria were determined a priori for this review. Measurements and Main Results: Experimental models that reproduce the various patterns of lung injury observed after HSCT have identified that both soluble and cellular inflammatory mediators contribute to the inflammation engendered during the development of IPS. To date, 10 preclinical murine models of the IPS spectrum have been established using various donor and host strain combinations used to study graft-versus-host disease (GVHD). This, as well as the demonstrated T cell dependency of IPS development in these models, supports the concept that the lung is a target of immune-mediated attack after HSCT. The most developed therapeutic strategy for IPS involves blocking TNF signaling with etanercept, which is currently being evaluated in clinical trials. Conclusions: IPS remains a frequently fatal complication that limits the broader use of allogeneic HSCT as a successful treatment modality. Faced with the clinical syndrome of IPS, one can categorize the disease entity with the appropriate tools, although cases of unclassifiable IPS will remain. Significant research efforts have resulted in a paradigm shift away from identifying noninfectious lung injury after HSCT solely as an idiopathic clinical syndrome and toward understanding IPS as a process involving aspects of both the adaptive and the innate immune response. Importantly, new laboratory insights are currently being translated to the clinic and will likely prove important to the development of future strategies to prevent or treat this serious disorder.",,"['Panoskaltsis-Mortari, Angela', 'Griese, Matthias', 'Madtes, David K.', 'Belperio, John A.', 'Haddad, Imad Y.', 'Folz, Rodney J.', 'Cooke, Kenneth R.', None]",,,,
,PMC,"Treatment of Yellow Fever Virus with an Adenovirus-Vectored Interferon, DEF201, in a Hamster Model",http://dx.doi.org/10.1128/AAC.01635-10,PMC3088275,,,"Interferon (IFN) is an innate immune response protein that is involved in the antiviral response during viral infection. Treatment of acute viral infections with exogenous interferon may be effective but is generally not feasible for clinical use due to many factors, including cost, stability, and availability. To overcome these limitations, an adenovirus type 5-vectored consensus alpha IFN, termed DEF201, was constructed as a potential way to deliver sustained therapeutic levels of systemic IFN. To demonstrate the efficacy of DEF201 against acute flaviviral disease, various concentrations of the construct were administered as a single intranasal dose prior to virus infection, which resulted in a dose-responsive, protective effect in a hamster model of yellow fever virus (YFV) disease. A DEF201 dose of 5 × 10(7) PFU/animal administered intranasally just prior to YFV challenge protected 100% of the animals, while a 10-fold lower DEF201 dose exhibited lower, although significant, levels of protection. Virus titers in the liver and serum and levels of serum alanine aminotransferase were all significantly reduced as a result of DEF201 administration at all doses tested. No toxicity, as indicated by weight loss or gross morbidity, was observed in non-YFV-infected animals treated with DEF201. Protection of YFV-infected animals was observed when DEF201 was delivered as early as 7 days prior to virus challenge and as late as 2 days after virus challenge, demonstrating effective prophylaxis and therapy in a hamster model of disease. Overall, it appears that DEF201 is effective in the treatment of YFV in a hamster model.",,"['Julander, Justin G.', 'Ennis, Jane', 'Turner, Jeffrey', 'Morrey, John D.']",,,,
,PMC,Inhaled innate immune ligands to prevent pneumonia,http://dx.doi.org/10.1111/j.1476-5381.2011.01237.x,PMC3085878,,,"Epithelial surfaces throughout the body continuously sample and respond to environmental stimuli. The accessibility of lung epithelium to inhaled therapies makes it possible to stimulate local antimicrobial defences with aerosolized innate immune ligands. This strategy has been shown to be effective in preclinical models, as delivery of innate immune ligands to the lungs of laboratory animals results in protection from subsequent challenge with microbial pathogens. Survival of the animal host in this setting correlates directly with killing of pathogens within the lungs, indicating the induction of a resistance mechanism. Resistance appears to be mediated primarily by activated epithelial cells rather than recruited leucocytes. Resistance reaches a peak within hours and persists for several days. Innate immune ligands can interact synergistically under some circumstances, and synergistic combinations of innate ligands delivered by aerosol are capable of inducing a high level of broad host resistance to bacteria, fungi and viruses. The induction of innate antimicrobial resistance within the lungs could have clinical applications in the prevention of lower respiratory tract infection in subjects transiently at high risk. These include cancer patients undergoing myeloablative chemotherapy, intubated patients being mechanically ventilated, vulnerable individuals during seasonal influenza epidemics, asthmatic subjects experiencing a respiratory viral infection, and healthy subjects exposed to virulent pathogens from a bioterror attack or emergent pandemic. In summary, stimulation of the lung epithelium to induce localized resistance to infection is a novel strategy whose clinical utility will be assessed in the near future. LINKED ARTICLES: This article is part of a themed issue on Respiratory Pharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-1",,"['Evans, Scott E', 'Tuvim, Michael J', 'Fox, Cory J', 'Sachdev, Nidhi', 'Gibiansky, Leonid', 'Dickey, Burton F']",,,,
,PMC,"Viral Infections of the Lower Respiratory Tract: Old Viruses, New Viruses, and the Role of Diagnosis",http://dx.doi.org/10.1093/cid/cir043,PMC3106235,,,"Viral infections of the lower respiratory tract cause an enormous disease burden in children, and the role of respiratory viruses in serious lower respiratory tract infections (LRTIs) in older adults is increasingly appreciated. Although viruses are responsible for a large proportion LRTIs, antibiotics are often prescribed. New diagnostic platforms have the potential to detect a wider range of established and newly discovered viruses with greater sensitivity. This will create additional challenges. Although it is clear that influenza, parainfluenza, respiratory syncytial virus, human metapneumovirus, and adenovirus are important causes of pneumonia, the role of rhinoviruses and some of the newly described viruses, including human coronaviruses and bocavirus, is harder to determine. Better diagnostic tests that establish the cause of LRTIs in children have the potential to both reduce overall antibiotic use and to improve the targeted use of antibiotics. In addition, rapid identification of viral infections can help control nosocomial transmission.",,"Pavia, Andrew T.",,,,
,PMC,Simultaneous Detection of Antibodies to Mouse Hepatitis Virus Recombinant Structural Proteins by a Microsphere-Based Multiplex Fluorescence Immunoassay,http://dx.doi.org/10.1128/CVI.00467-10,PMC3122517,,,"We describe a new microsphere-based multiplex fluorescent immunoassay (MFI) using recombinant mouse hepatitis virus (MHV) proteins to detect antibodies to coronaviruses in mouse and rat sera. All the recombinant proteins, including nucleocapsid (N) and 3 subunits of spike protein, S1, S2, and Smid, showed positive reactivity in MFI with mouse antisera to 4 MHV strains (MHV-S, -A59, -JHM, and -Nu67) and rat antiserum to a strain of sialodacryoadenitis virus (SDAV-681). The MFI was evaluated for its diagnostic power, with panels of mouse sera classified as positive or negative for anti-MHV antibodies by enzyme-linked immunosorbent assay (ELISA) using MHV virion antigen and indirect fluorescent antibody assay. The reactivities of 236 naturally infected mouse sera were examined; 227 samples were positive by MFI using S2 antigen (96% sensitivity), and 208 samples were positive using N antigen (88% sensitivity). Based on the assessment by MFI using the S2 and N antigens, only 3 serum samples showed double-negative results, indicating a false-negative rate of 1.3%. In 126 uninfected mouse sera, including 34 ELISA false-positive sera, only 7 samples showed false-positive results by MFI using either the S2 or N antigen (94% specificity). Similarly, the S2 and N antigen-based MFI was 98% sensitive and 100% specific in detecting anticoronavirus antibodies in rat sera. Thus, this MFI-based serologic assay using the S2 and N antigens promises to be a reliable diagnostic method, representing a highly sensitive and specific alternative to traditional ELISA for detection of coronavirus infections in laboratory mouse and rat colonies.",,"['Kunita, Satoshi', 'Kato, Kanako', 'Ishida, Miyuki', 'Hagiwara, Kozue', 'Kameda, Shuko', 'Ishida, Tomoko', 'Takakura, Akira', 'Goto, Kazuo', 'Sugiyama, Fumihiro', 'Yagami, Ken-ichi']",,,,
,PMC,Characterization of Protein–DNA Interactions Using Protein Microarrays,http://dx.doi.org/10.1101/pdb.prot5614,PMC5890440,,,,,"['Hu, Shaohui', 'Xie, Zhi', 'Blackshaw, Seth', 'Qian, Jiang', 'Zhu, Heng']",,,,
,PMC,"Coronaviruses: Propagation, Quantification, Storage, and Construction of Recombinant Mouse Hepatitis Virus",http://dx.doi.org/10.1002/9780471729259.mc15e01s21,PMC3119930,,,"The focus of this protocol is mouse hepatitis virus (MHV), with occasional references to other coronaviruses. Many of these protocols can be easily adapted to other coronaviruses. Basic protocols for propagating MHV in DBT and 17CL-1 cells; the storage, and titration of viral stocks; purification of MHV on sucrose gradients; and the generation of recombinant viruses by a cDNA assembly method and by targeted recombination, will be presented. Support protocols for the propagation of DBT, 17CL-1, and L2 cells used for growing and titrating MHV, for the growth of BHK-R cells and FCWF cells. The latter two cell lines are used for regenerating infectious MHV by an in vitro cDNA assembly protocol and by a targeted recombination protocol, respectively, allowing reverse genetic manipulation of these viruses. An additional support protocol for the maintenance of the large plasmids used for generating recombinant MHVs will also be presented.",,"['Leibowitz, Julian', 'Kaufman, Gili', 'Liu, Pinghua']",,,,
,PMC,Viral myocarditis: potential defense mechanisms within the cardiomyocyte against virus infection,http://dx.doi.org/10.2217/fmb.11.40,PMC3131135,,,"Virus infection can inflict significant damage on cardiomyocytes through direct injury and secondary immune reactions, leading to myocarditis and dilated cardiomyopathy. While viral myocarditis or cardiomyopathy is a complication of systemic infection of cardiotropic viruses, most individuals infected with the viruses do not develop significant cardiac disease. However, some individuals proceed to develop severe virus-mediated heart disease. Recent studies have shown that viral infection of cardiomyocytes is required for the development of myocarditis and subsequent cardiomyopathy. This suggests that viral infection of cardiomyocytes can be an important step that determines the pathogenesis of viral myocarditis during systemic infection. Accordingly, this article focuses on potential defense mechanisms within the cardiomyocyte against virus infection. Understanding of the cardiomyocyte defense against invading viruses may give us novel insights into the pathophysiology of viral myocarditis, and enable us to develop innovative strategies of diagnosis and treatment for this challenging clinical entity.",,"Yajima, Toshitaka",,,,
,PMC,Recent developments in anti-severe acute respiratory syndrome coronavirus chemotherapy,http://dx.doi.org/10.2217/fvl.11.33,PMC3136164,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in early 2003 to cause a very severe acute respiratory syndrome, which eventually resulted in a 10% case-fatality rate. Owing to excellent public health measures that isolated focus cases and their contacts, and the use of supportive therapies, the epidemic was suppressed to the point that further cases have not appeared since 2005. However, despite intensive research since then (over 3500 publications), it remains an untreatable disease. The potential for re-emergence of the SARS-CoV or a similar virus with unknown but potentially serious consequences remains high. This is due in part to the extreme genetic variability of RNA viruses such as the coronaviruses, the many animal reservoirs that seem to be able host the SARS-CoV in which reassortment or recombination events could occur and the ability coronaviruses have to transmit relatively rapidly from species to species in a short period of time. Thus, it seems prudent to continue to explore and develop antiviral chemotherapies to treat SARS-CoV infections. To this end, the various efficacious anti-SARS-CoV therapies recently published from 2007 to 2010 are reviewed in this article. In addition, compounds that have been tested in various animal models and were found to reduce virus lung titers and/or were protective against death in lethal models of disease, or otherwise have been shown to ameliorate the effects of viral infection, are also reported.",,"['Barnard, Dale L', 'Kumaki, Yohichi']",,,,
,PMC,Effect of a Short-term Fast on Ketamine–Xylazine Anesthesia in Rats,,PMC3103284,,,"Although ketamine–xylazine (KX) anesthesia is commonly used in rats, it is often reported to have an inconsistent anesthetic effect, with a prolonged induction time, an inadequate anesthetic plane, or a very short sleep time. Blood flow to the liver is known to shift after a meal in rats, perhaps explaining anesthetic variability among rats with variable prandial status. The current study tested the hypothesis that a short period of fasting (3 h) prior to induction with intraperitoneal KX anesthesia would provide a shorter time to recumbency, a longer total sleep time, and a more consistent loss of toe pinch response than would fed rats. Two groups of male Sprague–Dawley rats were used in blinded, crossover experiments. KX anesthesia was administered at 2 different doses (50 mg/kg–5 mg/kg and 70 mg/kg–7 mg/kg) after ad libitum feeding or a 3-h fast. There were no significant differences between groups in induction time, total sleep time, or loss of toe pinch response. We conclude that fasting rats for 3 h prior to KX intraperitoneal anesthesia does not affect induction time, total sleep time, loss of toe pinch response or reduce KX anesthetic variability in male Sprague–Dawley rats.",,"['Struck, Maggie B', 'Andrutis, Karl A', 'Ramirez, Harvey E', 'Battles, August H']",,,,
,PMC,Comparison of the Luminex xTAG Respiratory Viral Panel with xTAG Respiratory Viral Panel Fast for Diagnosis of Respiratory Virus Infections,http://dx.doi.org/10.1128/JCM.02090-10,PMC3122679,,,"Nucleic acid tests are sensitive and specific and provide a rapid diagnosis, making them invaluable for patient and outbreak management. Multiplex PCR assays have additional advantages in providing an economical and comprehensive panel for many common respiratory viruses. Previous reports have shown the utility of the xTAG respiratory viral panel (RVP) assay manufactured by Luminex Molecular Diagnostics for this purpose. A newer generation of this kit, released in Canada in early 2010, is designed to simplify the procedure and reduce the turnaround time by about 24 h. The assay methodology and targets included in this version of the kit are different; consequently, the objective of this study was to compare the detection of a panel of respiratory viral targets using the older Luminex xTAG RVP (RVP Classic) assay with that using the newer xTAG RVP Fast assay. This study included 334 respiratory specimens that had been characterized for a variety of respiratory viral targets; all samples were tested by both versions of the RVP assay in parallel. Overall, the RVP Classic assay was more sensitive than the RVP Fast assay (88.6% and 77.5% sensitivities, respectively) for all the viral targets combined. Targets not detected by the RVP Fast assay included primarily influenza B virus, parainfluenza virus type 2, and human coronavirus 229E. A small number of samples positive for influenza A virus, respiratory syncytial virus B, human metapneumovirus, and parainfluenza virus type 1 were not detected by the RVP Classic assay and in general had low viral loads.",,"['Pabbaraju, Kanti', 'Wong, Sallene', 'Tokaryk, Kara L.', 'Fonseca, Kevin', 'Drews, Steven J.']",,,,
,PMC,Myocarditis Caused by Human Parainfluenza Virus in an Immunocompetent Child Initially Associated with 2009 Influenza A (H1N1) Virus,http://dx.doi.org/10.1128/JCM.02638-10,PMC3122673,,,"The association between respiratory viruses and myocarditis has hardly ever been described. We report a case of acute myocarditis in an immunocompetent child associated with the presence of parainfluenza virus type 3 infection, in a context of recent influenza illness, confirmed by molecular and serological studies.",,"['Romero-Gómez, María P.', 'Guereta, Luis', 'Pareja-Grande, Julia', 'Martínez-Alarcón, José', 'Casas, Inmaculada', 'Ruiz-Carrascoso, Guillermo', 'de Ory, Fernando', 'Pozo, Francisco']",,,,
,PMC,Loop-Mediated Isothermal Amplification for Rapid and Reliable Diagnosis of Tuberculous Meningitis,http://dx.doi.org/10.1128/JCM.00824-10,PMC3122663,,,"Diagnosis of tuberculous meningitis (TBM) is often difficult. A reliable, simple, and rapid diagnostic test that can be performed in any standard laboratory could be helpful in TBM diagnosis. In this study, a loop-mediated isothermal amplification assay (LAMP) was evaluated to rapidly detect and diagnose TBM infection and was compared to the performance of nested PCR. Six specific primers were used to recognize the IS6110 genomic sequence from Mycobacterium tuberculosis, which included one forward outer primer, one reverse outer primer, two respective inner primers, and two loop primers. The optimum reaction temperature and time were 63°C and 60 min, respectively. Nested PCR was performed targeting the IS6110 region from M. tuberculosis using a commercial kit. The LAMP method yielded a sensitivity of 88.23% and a specificity of 80%, compared to the nested-PCR assay, which yielded a sensitivity of 52.9% and a specificity of 90% for TBM diagnosis. Comparative experiments showed that the LAMP assay is a rapid, sensitive, and specific method to detect TBM infection and that it is superior to the nested-PCR assay. LAMP is very simple, and it can be performed in any laboratory and in rural settings.",,"['Nagdev, Khushboo J.', 'Kashyap, Rajpal S.', 'Parida, Manmohan M.', 'Kapgate, Rajkumar C.', 'Purohit, Hemant J.', 'Taori, Girdhar M.', 'Daginawala, Hatim F.']",,,,
,PMC,Antigenic modules in the N-terminal S1 region of the transmissible gastroenteritis virus spike protein,http://dx.doi.org/10.1099/vir.0.027607-0,PMC3139418,,,"The N-terminal S1 region of the transmissible gastroenteritis virus (TGEV) spike (S) glycoprotein contains four antigenic sites (C, B, D and A, from the N- to the C-terminal end) and is engaged in host-cell receptor recognition. The most N-terminal portion of the S1 region, which comprises antigenic sites C and B, is needed for the enteric tropism of TGEV, whereas the major antigenic site A at the C-terminal moiety is required for both respiratory and enteric cell tropism, and is engaged in recognition of the aminopeptidase N (APN) receptor. This study determined the kinetics for binding of a soluble S1 protein to the APN protein. Moreover, the S1 region of the TGEV S protein was dissected, with the aim of identifying discrete modules displaying unique antigenic sites and receptor-binding functions. Following protease treatments and mammalian cell expression methods, four modules or domains (D1–D4) were defined at the S1 region. Papain treatment identified an N-terminal domain (D1) resistant to proteolysis, whereas receptor binding defined a soluble and functional APN receptor-binding domain (D3). This domain was recognized by neutralizing antibodies belonging to the antigenic site A and therefore could be used as an immunogen for the prevention of viral infection. The organization of the four modules in the S1 region of the TGEV S glycoprotein is discussed.",,"['Reguera, Juan', 'Ordoño, Desiderio', 'Santiago, César', 'Enjuanes, Luis', 'Casasnovas, José M.']",,,,
,PMC,Immunoglobulin G (IgG) Expression in Human Umbilical Cord Endothelial Cells,http://dx.doi.org/10.1369/0022155411400871,PMC3201178,,,"Traditional views hold that immunoglobulin G (IgG) in the human umbilical cord is internalized by human umbilical endothelial cells for passive immunity. In this study, the protein and mRNA transcripts of IgG were found in the cytoplasm of human umbilical endothelial cells by immunohistochemistry, in situ hybridization, and reverse transcription PCR (RT-PCR). The essential enzymes for IgG synthesis and assembling, RAG1 (recombination activating gene 1), RAG2, and variable (V), diversity (D), and joining (J) segments for recombination of IgG, were also found in these cells by RT-PCR and real-time PCR. These results indicate that umbilical endothelial cells are capable of synthesizing IgG with properties similar to those of immune cells and that they may play additional roles besides lining the vessels and transporting IgG.",,"['Zhao, Yingying', 'Liu, Yuxuan', 'Chen, Zhengshan', 'Korteweg, Christine', 'Gu, Jiang']",,,,
,PMC,"Thoracic computerized tomographic (CT) findings in 2009 influenza A (H1N1) virus infection in Isfahan, Iran",,PMC3214369,22091280,CC BY-NC-SA,"BACKGROUND: Pandemic 2009 H1N1 influenza A virus arrived at Isfahan in August 2009. The virus is still circulating in the world. The abnormal thoracic computerized tomographic (CT) scan findings vary widely among the studies of 2009 H1N1 influenza. We evaluated the thoracic CT findings in patients with 2009 H1N1 virus infection to describe findings compared to previously reported findings, and to suggest patterns that may be suggestive for 2009 influenza A (H1N1) in an appropriate clinical setting. METHODS: Retrospectively, the archive of all patients with a diagnosis of 2009 H1N1 influenza A were reviewed, in Al-Zahra Hospital in Isfahan, central Iran, between September 23(rd) 2009 to February 20(th) 2010. Out of 216 patients with confirmed 2009 influenza A (H1N1) virus, 26 cases with abnormal CT were enrolled in the study. Radiologic findings were characterized by the type and pattern of opacities and zonal distribution. RESULTS: Patchy infiltration (34.6%), lobar consolidation (30.8%), and interstitial infiltration (26.9%) with airbronchogram (38.5%) were the predominant findings in our patients. Bilateral distribution was seen in 80.8% of the patients. Only one patient (3.8%) showed ground-glass opacity, predominant radiographic finding in the previous reports and severe acute respiratory syndrome (SARS). CONCLUSIONS: The most common thoracic CT findings in pandemic H1N1 were patchy infiltration, lobar consolidation, and interstitial infiltration with airbronchogram and bilateral distribution. While these findings can be associated with other infections; they may be suggestive to 2009 influenza A (H1N1) in the appropriate clinical setting. Various radiographic patterns can be seen in thoracic CT scans of the influenza patients. Imaging findings are nonspecific.",2011 May,"['Rostami, Mojtaba', 'Javadi, Abbas-Ali', 'Khorvash, Farzin', 'Mostafavizadeh, Kamyar', 'Adibi, Atoosa', 'Babak, Anahita', 'Ataei, Behrooz', 'Meidani, Mohsen', 'Naeini, Alireza Emami', 'Salehi, Hasan', 'Avijgan, Majid', 'Yazdani, Mohammad Reza', 'Rezaei, Farshid']",J Res Med Sci,,,
,PMC,"Development of a chromogenic in situ hybridization for Giardia duodenalis and its application in canine, feline, and porcine intestinal tissues samples",http://dx.doi.org/10.1177/1040638711404151,PMC3173878,,,"In the present study, a chromogenic in situ hybridization for the identification of Giardia duodenalis in paraffin-embedded tissue samples was developed. The sensitivity and specificity of the probe was validated by testing it on cultured reference samples of different assemblages of G. duodenalis as well as culture and tissue samples containing other protozoa and infectious agents. The probe gave a positive reaction with the Giardia samples and a negative reaction with all other samples. Further, the probe was used for screening of histological slides of intestine from different animal species (99 canine samples, 85 feline samples, and 202 porcine samples) for the presence of G. duodenalis trophozoites. With this assay, the parasites were detected in samples from 8 dogs (8.08%), 6 cats (7.06%), and zero pigs. The results clearly indicate that the described method is useful for detection of Giardia trophozoites in routinely processed intestinal tissue of different animal species.",,"['Weissenböck, Herbert', 'Ondrovics, Martina', 'Gurtner, Susanne', 'Schiessl, Peter', 'Mostegl, Meike M.', 'Richter, Barbara']",,,,
,PMC,Chimpanzee-Human Monoclonal Antibodies for Treatment of Chronic Poliovirus Excretors and Emergency Postexposure Prophylaxis,http://dx.doi.org/10.1128/JVI.02553-10,PMC3126281,,,"Six poliovirus-neutralizing Fabs were recovered from a combinatorial Fab phage display library constructed from bone marrow-derived lymphocytes of immunized chimpanzees. The chimeric chimpanzee-human full-length IgGs (hereinafter called monoclonal antibodies [MAbs]) were generated by combining a chimpanzee IgG light chain and a variable domain of heavy chain with a human constant Fc region. The six MAbs neutralized vaccine strains and virulent strains of poliovirus. Five MAbs were serotype specific, while one MAb cross-neutralized serotypes 1 and 2. Epitope mapping performed by selecting and sequencing antibody-resistant viral variants indicated that the cross-neutralizing MAb bound between antigenic sites 1 and 2, thereby covering the canyon region containing the receptor-binding site. Another serotype 1-specific MAb recognized a region located between antigenic sites 2 and 3 that included parts of capsid proteins VP1 and VP3. Both serotype 2-specific antibodies recognized antigenic site 1. No escape mutants to serotype 3-specific MAbs could be generated. The administration of a serotype 1-specific MAb to transgenic mice susceptible to poliovirus at a dose of 5 μg/mouse completely protected them from paralysis after challenge with a lethal dose of wild-type poliovirus. Moreover, MAb injection 6 or 12 h after virus infection provided significant protection. The MAbs described here could be tested in clinical trials to determine whether they might be useful for treatment of immunocompromised chronic virus excretors and for emergency protection of contacts of a paralytic poliomyelitis case.",,"['Chen, Zhaochun', 'Chumakov, Konstantin', 'Dragunsky, Eugenia', 'Kouiavskaia, Diana', 'Makiya, Michelle', 'Neverov, Alexander', 'Rezapkin, Gennady', 'Sebrell, Andrew', 'Purcell, Robert']",,,,
,PMC,Vesicular Stomatitis Virus-Based H5N1 Avian Influenza Vaccines Induce Potent Cross-Clade Neutralizing Antibodies in Rhesus Macaques,http://dx.doi.org/10.1128/JVI.02491-10,PMC3126271,,,We analyzed the ability of a vaccine vector based on vesicular stomatitis virus (VSV) to induce a neutralizing antibody (NAb) response to avian influenza viruses (AIVs) in rhesus macaques. Animals vaccinated with vectors expressing either strain A/Hong Kong/156/1997 or strain A/Vietnam/1203/2004 H5 hemagglutinin (HA) were able to generate robust NAb responses. The ability of the vectors to induce NAbs against homologous and heterologous AIVs after a single dose was dependent upon the HA antigen incorporated into the VSV vaccine. The vectors expressing strain A/Vietnam/1203/2004 H5 HA were superior to those expressing strain A/Hong Kong/156/1997 HA at inducing cross-clade NAbs.,,"['Schwartz, Jennifer A.', 'Buonocore, Linda', 'Suguitan, Amorsolo', 'Hunter, Meredith', 'Marx, Preston A.', 'Subbarao, Kanta', 'Rose, John K.']",,,,
,PMC,Distinct Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury Pathways in Two Different Nonhuman Primate Species,http://dx.doi.org/10.1128/JVI.02395-10,PMC3126247,,,"Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), caused by influenza A virus H5N1 and severe acute respiratory syndrome coronavirus (SARS-CoV), supposedly depend on activation of the oxidative-stress machinery that is coupled with innate immunity, resulting in a strong proinflammatory host response. Inflammatory cytokines, such as interleukin 1β (IL-1β), IL-8, and IL-6, play a major role in mediating and amplifying ALI/ARDS by stimulating chemotaxis and activation of neutrophils. To obtain further insight into the pathogenesis of SARS-CoV-associated ALI, we compared SARS-CoV infections in two different nonhuman primate species, cynomolgus macaques and African green monkeys. Viral titers in the upper and lower respiratory tract were not significantly different in SARS-CoV-infected macaques and African green monkeys. Inflammatory cytokines that play a major role in mediating and amplifying ALI/ARDS or have neutrophil chemoattractant activity, such as IL-6, IL-8, CXCL1, and CXCL2, were, however, induced only in macaques. In contrast, other proinflammatory cytokines and chemokines, including osteopontin and CCL3, were upregulated in the lungs of African green monkeys to a significantly greater extent than in macaques. Because African green monkeys developed more severe ALI than macaques, with hyaline membrane formation, some of these differentially expressed proinflammatory genes may be critically involved in development of the observed pathological changes. Induction of distinct proinflammatory genes after SARS-CoV infection in different nonhuman primate species needs to be taken into account when analyzing outcomes of intervention strategies in these species.",,"['Smits, Saskia L.', 'van den Brand, Judith M. A.', 'de Lang, Anna', 'Leijten, Lonneke M. E.', 'van IJcken, Wilfred F.', 'van Amerongen, Geert', 'Osterhaus, Albert D. M. E.', 'Andeweg, Arno C.', 'Haagmans, Bart L.']",,,,
,PMC,Bovine Plasmacytoid Dendritic Cells Are the Major Source of Type I Interferon in Response to Foot-and-Mouth Disease Virus In Vitro and In Vivo,http://dx.doi.org/10.1128/JVI.02495-10,PMC3126242,,,"Type I interferons (alpha/beta interferons [IFN-α/β]) are the main innate cytokines that are able to induce a cellular antiviral state, thereby limiting viral replication and disease pathology. Plasmacytoid dendritic cells (pDCs) play a crucial role in the control of viral infections, especially in response to viruses that have evolved mechanisms to block the type I IFN signal transduction pathway. Using density gradient separation and cell sorting, we have highly enriched a population of bovine cells capable of producing high levels of biologically active type I IFN. These cells represented less than 0.1% of the total lymphocyte population in blood, pseudoafferent lymph, and lymph nodes. Phenotypic analysis identified these cells as bovine pDCs (CD3(−) CD14(−) CD21(−) CD11c(−) NK(−) TCRδ(−) CD4(+) MHC II(+) CD45RB(+) CD172a(+) CD32(+)). High levels of type I IFN were generated by these cells in vitro in response to Toll-like receptor 9 (TLR-9) agonist CpG and foot-and-mouth disease virus (FMDV) immune complexes. In contrast, immune complexes formed with UV-inactivated FMDV or FMDV empty capsids failed to elicit a type I IFN response. Depletion of CD4 cells in vivo resulted in levels of type I IFN in serum early during FMDV infection that were significantly lower than those for control animals. In conclusion, pDCs interacting with immune-complexed virus are the major source of type I interferon production during acute FMDV infection in cattle.",,"['Reid, Elizabeth', 'Juleff, Nicholas', 'Gubbins, Simon', 'Prentice, Helen', 'Seago, Julian', 'Charleston, Bryan']",,,,
,PMC,Mobility and Interactions of Coronavirus Nonstructural Protein 4,http://dx.doi.org/10.1128/JVI.00042-11,PMC3126240,,,"Green fluorescent protein (GFP)-tagged mouse hepatitis coronavirus nonstructural protein 4 (nsp4) was shown to localize to the endoplasmic reticulum (ER) and to be recruited to the coronavirus replicative structures. Fluorescence loss in photobleaching and fluorescence recovery after photobleaching experiments demonstrated that while the membranes of the ER are continuous with those harboring the replicative structures, the mobility of nsp4 at the latter structures is relatively restricted. In agreement with that observation, nsp4 was shown to be engaged in homotypic and heterotypic interactions, the latter with nsp3 and nsp6. In addition, the coexpression of nsp4 with nsp3 affected the subcellular localization of the two proteins.",,"['Hagemeijer, Marne C.', 'Ulasli, Mustafa', 'Vonk, Annelotte M.', 'Reggiori, Fulvio', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.']",,,,
,PMC,Early Induction of Autophagy in Human Fibroblasts after Infection with Human Cytomegalovirus or Herpes Simplex Virus 1,http://dx.doi.org/10.1128/JVI.02435-10,PMC3126239,,,"The infection of human fetal foreskin fibroblasts (HFFF2) with human cytomegalovirus (HCMV) resulted in the induction of autophagy. This was demonstrated by the increased lipidation of microtubule-associated protein 1 light chain 3 (LC3), a hallmark of autophagy, and by the visualization of characteristic vesicles within infected cells. The response was detected first at 2 h postinfection and persisted for at least 3 days. De novo protein synthesis was not required for the effect, since HCMV that was irradiated with UV light also elicited the response, and furthermore the continuous presence of cycloheximide did not prevent induction. Infection with herpes simplex virus type 1 (HSV-1) under conditions that inhibited viral gene expression provoked autophagy, whereas UV-irradiated respiratory syncytial virus did not. The induction of autophagy occurred when cells were infected with HCMV or HSV-1 that was gradient purified, but HCMV dense bodies and HSV-1 light particles, each of which lack nucleocapsids and genomes, were inactive. The depletion of regulatory proteins Atg5 and Atg7, which are required for autophagy, reduced LC3 modification in response to infection but did not result in any detectable difference in viral or cellular gene expression at early times after infection. The electroporation of DNA into HFFF2 cultures induced the lipidation of LC3 but double-stranded RNA did not, even though both agents stimulated an innate immune response. The results show a novel, early cellular response to the presence of the incoming virion and additionally demonstrate that autophagy can be induced by the presence of foreign DNA within cells.",,"['McFarlane, Steven', 'Aitken, James', 'Sutherland, Jane S.', 'Nicholl, Mary Jane', 'Preston, Valerie G.', 'Preston, Chris M.']",,,,
,PMC,Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response,http://dx.doi.org/10.1128/JVI.02232-10,PMC3126222,,,"The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) can be proteolytically activated by cathepsins B and L upon viral uptake into target cell endosomes. In contrast, it is largely unknown whether host cell proteases located in the secretory pathway of infected cells and/or on the surface of target cells can cleave SARS S. We along with others could previously show that the type II transmembrane protease TMPRSS2 activates the influenza virus hemagglutinin and the human metapneumovirus F protein by cleavage. Here, we assessed whether SARS S is proteolytically processed by TMPRSS2. Western blot analysis revealed that SARS S was cleaved into several fragments upon coexpression of TMPRSS2 (cis-cleavage) and upon contact between SARS S-expressing cells and TMPRSS2-positive cells (trans-cleavage). cis-cleavage resulted in release of SARS S fragments into the cellular supernatant and in inhibition of antibody-mediated neutralization, most likely because SARS S fragments function as antibody decoys. trans-cleavage activated SARS S on effector cells for fusion with target cells and allowed efficient SARS S-driven viral entry into targets treated with a lysosomotropic agent or a cathepsin inhibitor. Finally, ACE2, the cellular receptor for SARS-CoV, and TMPRSS2 were found to be coexpressed by type II pneumocytes, which represent important viral target cells, suggesting that SARS S is cleaved by TMPRSS2 in the lung of SARS-CoV-infected individuals. In summary, we show that TMPRSS2 might promote viral spread and pathogenesis by diminishing viral recognition by neutralizing antibodies and by activating SARS S for cell-cell and virus-cell fusion.",,"['Glowacka, Ilona', 'Bertram, Stephanie', 'Müller, Marcel A.', 'Allen, Paul', 'Soilleux, Elizabeth', 'Pfefferle, Susanne', 'Steffen, Imke', 'Tsegaye, Theodros Solomon', 'He, Yuxian', 'Gnirss, Kerstin', 'Niemeyer, Daniela', 'Schneider, Heike', 'Drosten, Christian', 'Pöhlmann, Stefan']",,,,
,PMC,Contact Transmission of Tobacco Mosaic Virus: a Quantitative Analysis of Parameters Relevant for Virus Evolution,http://dx.doi.org/10.1128/JVI.00057-11,PMC3126215,,,"Transmission between hosts is required for the maintenance of parasites in the host population and determines their ultimate evolutionary success. The transmission ability of parasites conditions their evolution in two ways: on one side, it affects the genetic structure of founded populations in new hosts. On the other side, parasite traits that increase transmission efficiency will be selected for. Therefore, knowledge of the factors and parameters that determine transmission efficiency is critical to predict the evolution of parasites. For plant viruses, little is known about the parameters of contact transmission, a major way of transmission of important virus genera and species. Here, we analyze the factors determining the efficiency of contact transmission of Tobacco mosaic virus (TMV) that may affect virus evolution. As it has been reported for other modes of transmission, the rate of TMV transmission by contact depended on the contact opportunities between an infected and a noninfected host. However, TMV contact transmission differed from other modes of transmission, in that a positive correlation between the virus titer in the source leaf and the rate of transmission was not found within the range of our experimental conditions. Other factors associated with the nature of the source leaf, such as leaf age and the way in which it was infected, had an effect on the rate of transmission. Importantly, contact transmission resulted in severe bottlenecks, which did not depend on the host susceptibility to infection. Interestingly, the effective number of founders initiating the infection of a new host was highly similar to that reported for aphid-transmitted plant viruses, suggesting that this trait has evolved to an optimum value.",,"['Sacristán, Soledad', 'Díaz, Maira', 'Fraile, Aurora', 'García-Arenal, Fernando']",,,,
,PMC,Assembly of Alphavirus Replication Complexes from RNA and Protein Components in a Novel trans-Replication System in Mammalian Cells,http://dx.doi.org/10.1128/JVI.00085-11,PMC3126202,,,"For positive-strand RNA viruses, the viral genomic RNA also acts as an mRNA directing the translation of the replicase proteins of the virus. Replication takes place in association with cytoplasmic membranes, which are heavily modified to create specific replication compartments. Here we have expressed by plasmid DNA transfection the large replicase polyprotein of Semliki Forest virus (SFV) in mammalian cells from a nonreplicating mRNA and provided a separate RNA containing the replication signals. The replicase proteins were able to efficiently and specifically replicate the template in trans, leading to accumulation of RNA and marker gene products expressed from the template RNA. The replicase proteins and double-stranded RNA replication intermediates localized to structures similar to those seen in SFV-infected cells. Using correlative light electron microscopy (CLEM) with fluorescent marker proteins to relocate those transfected cells, in which active replication was ongoing, abundant membrane modifications, representing the replication complex spherules, were observed both at the plasma membrane and in intracellular endolysosomes. Thus, replication complexes are faithfully assembled and localized in the trans-replication system. We demonstrated, using CLEM, that the replication proteins alone or a polymerase-negative polyprotein mutant together with the template did not give rise to spherule formation. Thus, the trans-replication system is suitable for cell biological dissection and examination in a mammalian cell environment, and similar systems may be possible for other positive-strand RNA viruses.",,"['Spuul, Pirjo', 'Balistreri, Giuseppe', 'Hellström, Kirsi', 'Golubtsov, Andrey V.', 'Jokitalo, Eija', 'Ahola, Tero']",,,,
,PMC,The Polypyrimidine Tract-Binding Protein Affects Coronavirus RNA Accumulation Levels and Relocalizes Viral RNAs to Novel Cytoplasmic Domains Different from Replication-Transcription Sites,http://dx.doi.org/10.1128/JVI.00195-11,PMC3126201,,,"The coronavirus (CoV) discontinuous transcription mechanism is driven by long-distance RNA-RNA interactions between transcription-regulating sequences (TRSs) located at the 5′ terminal leader (TRS-L) and also preceding each mRNA-coding sequence (TRS-B). The contribution of host cell proteins to CoV transcription needs additional information. Polypyrimidine tract-binding protein (PTB) was reproducibly identified in association with positive-sense RNAs of transmissible gastroenteritis coronavirus (TGEV) TRS-L and TRS-B by affinity chromatography and mass spectrometry. A temporal regulation of PTB cytoplasmic levels was observed during infection, with a significant increase from 7 to 16 h postinfection being inversely associated with a decrease in viral replication and transcription. Silencing the expression of PTB with small interfering RNA in two cell lines (Huh7 and HEK 293T) led to a significant increase of up to 4-fold in mRNA levels and virus titer, indicating a negative effect of PTB on CoV RNA accumulation. During CoV infection, PTB relocalized from the nucleus to novel cytoplasmic structures different from replication-transcription sites in which stress granule markers T-cell intracellular antigen-1 (TIA-1) and TIA-1-related protein (TIAR) colocalized. PTB was detected in these modified stress granules in TGEV-infected swine testis cells but not in stress granules induced by oxidative stress. Furthermore, viral genomic and subgenomic RNAs were detected in association with PTB and TIAR. These cytoplasmic ribonucleoprotein complexes might be involved in posttranscriptional regulation of virus gene expression.",,"['Sola, Isabel', 'Galán, Carmen', 'Mateos-Gómez, Pedro A.', 'Palacio, Lorena', 'Zúñiga, Sonia', 'Cruz, Jazmina L.', 'Almazán, Fernando', 'Enjuanes, Luis']",,,,
,PMC,The Neutralization Breadth of HIV-1 Develops Incrementally over Four Years and Is Associated with CD4(+) T Cell Decline and High Viral Load during Acute Infection,http://dx.doi.org/10.1128/JVI.00198-11,PMC3126191,,,"An understanding of how broadly neutralizing activity develops in HIV-1-infected individuals is needed to guide vaccine design and immunization strategies. Here we used a large panel of 44 HIV-1 envelope variants (subtypes A, B, and C) to evaluate the presence of broadly neutralizing antibodies in serum samples obtained 3 years after seroconversion from 40 women enrolled in the CAPRISA 002 acute infection cohort. Seven of 40 participants had serum antibodies that neutralized more than 40% of viruses tested and were considered to have neutralization breadth. Among the samples with breadth, CAP257 serum neutralized 82% (36/44 variants) of the panel, while CAP256 serum neutralized 77% (33/43 variants) of the panel. Analysis of longitudinal samples showed that breadth developed gradually starting from year 2, with the number of viruses neutralized as well as the antibody titer increasing over time. Interestingly, neutralization breadth peaked at 4 years postinfection, with no increase thereafter. The extent of cross-neutralizing activity correlated with CD4(+) T cell decline, viral load, and CD4(+) T cell count at 6 months postinfection but not at later time points, suggesting that early events set the stage for the development of breadth. However, in a multivariate analysis, CD4 decline was the major driver of this association, as viral load was not an independent predictor of breadth. Mapping of the epitopes targeted by cross-neutralizing antibodies revealed that in one individual these antibodies recognized the membrane-proximal external region (MPER), while in two other individuals, cross-neutralizing activity was adsorbed by monomeric gp120 and targeted epitopes that involved the N-linked glycan at position 332 in the C3 region. Serum antibodies from the other four participants targeted quaternary epitopes, at least 2 of which were PG9/16-like and depended on the N160 and/or L165 residue in the V2 region. These data indicate that fewer than 20% of HIV-1 subtype C-infected individuals develop antibodies with cross-neutralizing activity after 3 years of infection and that these antibodies target different regions of the HIV-1 envelope, including as yet uncharacterized epitopes.",,"['Gray, Elin S.', 'Madiga, Maphuti C.', 'Hermanus, Tandile', 'Moore, Penny L.', 'Wibmer, Constantinos Kurt', 'Tumba, Nancy L.', 'Werner, Lise', 'Mlisana, Koleka', 'Sibeko, Sengeziwe', 'Williamson, Carolyn', 'Abdool Karim, Salim S.', 'Morris, Lynn', None]",,,,
,PMC,Structure and Functional Relevance of a Transcription-Regulating Sequence Involved in Coronavirus Discontinuous RNA Synthesis,http://dx.doi.org/10.1128/JVI.02317-10,PMC3126183,,,"Transmissible gastroenteritis coronavirus (TGEV) genomic RNA transcription generates 5′- and 3′-coterminal subgenomic mRNAs. This process involves a discontinuous step during the synthesis of minus-sense RNA that is modulated by transcription-regulating sequences located at the 3′ end of the leader (TRS-L) and also preceding each viral gene (TRS-Bs). TRSs include a highly conserved core sequence (CS) (5′-CUAAAC-3′) and variable flanking sequences. It has been previously proposed that TRS-Bs act as attenuation or stop signals during the synthesis of minus-sense RNAs. The nascent minus-stranded RNA would then be transferred by a template switch process to the TRS-L, which acts as the acceptor RNA. To study whether the TRS-L is structured and to determine whether this structure has a functional impact on genomic and subgenomic viral RNA synthesis, we have used a combination of nuclear magnetic resonance (NMR) spectroscopy and UV thermal denaturation approaches together with site-directed mutagenesis and in vivo transcriptional analyses. The results indicated that a 36-nucleotide oligomer encompassing the wild-type TRS-L forms a structured hairpin closed by an apical AACUAAA heptaloop. This loop contains most of the CS and is isolated from a nearby internal loop by a short Watson-Crick base-paired stem. TRS-L mutations altering the structure and the stability of the TRS-L hairpin affected replication and transcription, indicating the requirement of a functional RNA hairpin structure in these processes.",,"['Dufour, David', 'Mateos-Gomez, Pedro A.', 'Enjuanes, Luis', 'Gallego, José', 'Sola, Isabel']",,,,
,PMC,New Academic Partnerships in Global Health: Innovations at Mount Sinai School of Medicine,http://dx.doi.org/10.1002/msj.20257,PMC3190974,,,"Global health has become an increasingly important focus of education, research, and clinical service in North American universities and academic health centers. Today there are at least 49 academically based global health programs in the United States and Canada, as compared with only one in 1999. A new academic society, the Consortium of Universities for Global Health, was established in 2008 and has grown significantly. This sharp expansion reflects convergence of 3 factors: (1) rapidly growing student and faculty interest in global health; (2) growing realization–powerfully catalyzed by the acquired immune deficiency syndrome epidemic, the emergence of other new infections, climate change, and globalization–that health problems are interconnected, cross national borders, and are global in nature; and (3) rapid expansion in resources for global health. This article examines the evolution of the concept of global health and describes the driving forces that have accelerated interest in the field. It traces the development of global health programs in academic health centers in the United States. It presents a blueprint for a new school-wide global health program at Mount Sinai School of Medicine. The mission of that program, Mount Sinai Global Health, is to enhance global health as an academic field of study within the Mount Sinai community and to improve the health of people around the world. Mount Sinai Global Health is uniting and building synergies among strong, existing global health programs within Mount Sinai; it is training the next generation of physicians and health scientists to be leaders in global health; it is making novel discoveries that translate into blueprints for improving health worldwide; and it builds on Mount Sinai’s long and proud tradition of providing medical and surgical care in places where need is great and resources few.",,"['Landrigan, Philip J.', 'Ripp, Jonathan', 'Murphy, Ramon J. C.', 'Claudio, Luz', 'Jao, Jennifer', 'Hexom, Braden', 'Bloom, Harrison G.', 'Shirazian, Taraneh', 'Elahi, Ebby', 'Koplan, Jeffrey P.']",,,,
,PMC,The immuno-pathophysiology of multiple sclerosis,http://dx.doi.org/10.1016/j.ncl.2010.12.009,PMC3080042,,,,,"['Wu, Gregory F.', 'Alvarez, Enrique']",,,,
,PMC,Inhibitory C-type lectin receptors in myeloid cells,http://dx.doi.org/10.1016/j.imlet.2010.10.005,PMC3061320,20934454,CC BY,"C-type lectin receptors encoded by the natural killer gene complex play critical roles in enabling NK cell discrimination between self and non-self. In recent years, additional genes at this locus have been identified with patterns of expression that extend to cells of the myeloid lineage where many of the encoded inhibitory receptors have equally important functions as regulators of immune homeostasis. In the present review we highlight the roles of some of these receptors including recent insights gained with regard to the identification of exogenous and endogenous ligands, mechanisms of cellular inhibition and activation, regulated expression within different cellular and immune contexts, as well as functions that include the regulation of bone homeostasis and involvement in autoimmunity.",2011 Apr 30,"['Redelinghuys, Pierre', 'Brown, Gordon D.']",Immunol Lett,,,
,PMC,Two-stepping through time: mammals and viruses,http://dx.doi.org/10.1016/j.tim.2011.03.006,PMC3567447,,,"Recent studies have identified ancient virus genomes preserved as fossils within diverse animal genomes. These fossils have led to the revelation that a broad range of mammalian virus families are older and more ubiquitous than previously appreciated. Long-term interactions between viruses and their hosts often develop into genetic arms races, where both parties continually jockey for evolutionary dominance. It is difficult to imagine how mammalian hosts have kept pace in the evolutionary race against rapidly evolving viruses over large expanses of time, given their much slower evolutionary rates. However, recent data has begun to reveal the evolutionary strategy of slowly-evolving hosts. We review these data, and suggest a modified arms race model where the evolutionary possibilities of viruses are relatively constrained. Such a model could allow more accurate forecasting of virus evolution.",,"['Meyerson, Nicholas R.', 'Sawyer, Sara L.']",,,,
,PMC,Anti-helminth compound niclosamide downregulates Wnt Signaling and elicits antitumor responses in tumors with activating APC mutations,http://dx.doi.org/10.1158/0008-5472.CAN-10-3978,PMC3117125,,,"Wnt/β-catenin pathway activation caused by APC mutations occurs in approximately 80% of sporadic colorectal cancers. The anti-helminth compound niclosamide downregulates components of the Wnt pathway, specifically Dishevelled-2 (Dvl2) expression, resulting in diminished downstream β-catenin signaling. In this study, we determined if niclosamide could inhibit the Wnt/ β-catenin pathway in human colorectal cancers and whether its inhibition might elicit antitumor effects in the presence of APC mutations. We found that niclosamide inhibited Wnt/ β-catenin pathway activation, downregulated Dvl2, decreased downstream β-catenin signaling and exerted anti-proliferative effects in human colon cancer cell lines and colorectal cancer cells isolated by surgical resection of metastatic disease, regardless of mutations in APC. In contrast, inhibition of NF-κB or mTOR did not exert similar anti-proliferative effects in these colorectal cancer model systems. In mice implanted with human colorectal cancer xenografts, orally administered niclosamide was well tolerated, achieved plasma and tumor levels associated with biologic activity and led to tumor control. Our findings support clinical explorations to reposition niclosamide for treatment of colorectal cancer.",,"['Osada, Takuya', 'Chen, Minyong', 'Yang, Xiao Yi', 'Spasojevic, Ivan', 'Vandeusen, Jeffrey B.', 'Hsu, David', 'Clary, Bryan M.', 'Clay, Timothy M.', 'Chen, Wei', 'Morse, Michael A.', 'Lyerly, H. Kim']",,,,
,PMC,Multifaceted roles for lipids in viral infection,http://dx.doi.org/10.1016/j.tim.2011.03.007,PMC3130080,,,"Viruses have evolved complex and dynamic interactions with their host cell. In recent years, we have gained insight into the expanding roles for cellular lipids in the viral life cycle. In particular, viruses target lipid signaling, synthesis, and metabolism to remodel their host cells into an environment that is optimal for their replication. This review highlights examples from different viruses that illustrate the importance of these diverse virus-lipid interactions.",,"['Heaton, Nicholas S.', 'Randall, Glenn']",,,,
,PMC,Activation and maturation of SARS-CoV main protease,http://dx.doi.org/10.1007/s13238-011-1034-1,PMC4875205,,,"The worldwide outbreak of the severe acute respiratory syndrome (SARS) in 2003 was due to the transmission of SARS coronavirus (SARS-CoV). The main protease (M(pro)) of SARS-CoV is essential for the viral life cycle, and is considered to be an attractive target of anti-SARS drug development. As a key enzyme for proteolytic processing of viral polyproteins to produce functional non-structure proteins, M(pro) is first auto-cleaved out of polyproteins. The monomeric form of M(pro) is enzymatically inactive, and it is activated through homo-dimerization which is strongly affected by extra residues to both ends of the mature enzyme. This review provides a summary of the related literatures on the study of the quaternary structure, activation, and self-maturation of M(pro) over the past years.",,"['Xia, Bin', 'Kang, Xue']",,,,
,PMC,SUBCELLULAR LOCATION AND TOPOLOGY OF SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS ENVELOPE PROTEIN,http://dx.doi.org/10.1016/j.virol.2011.03.029,PMC4726981,,,"Severe acute respiratory syndrome (SARS) coronavirus (CoV) envelope (E) protein is a transmembrane protein. Several subcellular locations and topological conformations of E protein have been proposed. To identify the correct ones, polyclonal and monoclonal antibodies specific for the amino or the carboxy terminus of E protein, respectively, were generated. E protein was mainly found in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) of cells transfected with a plasmid encoding E protein or infected with SARS-CoV. No evidence of E protein presence in the plasma membrane was found by using immunofluorescence, immunoelectron microscopy and cell surface protein labeling. In addition, measurement of plasma membrane voltage gated ion channel activity by whole-cell patch clamp suggested that E protein was not present in the plasma membrane. A topological conformation in which SARS-CoV E protein amino terminus is oriented towards the lumen of intracellular membranes and carboxy terminus faces cell cytoplasm is proposed.",,"['Nieto-Torres, Jose L.', 'DeDiego, Marta L.', 'Álvarez, Enrique', 'Jiménez-Guardeño, Jose M.', 'Regla-Nava, Jose A.', 'Llorente, Mercedes', 'Kremer, Leonor', 'Shuo, Shen', 'Enjuanes, Luis']",,,,
,PMC,Secretoneurin stimulates the production and release of luteinizing hormone in mouse LβT2 gonadotropin cells,http://dx.doi.org/10.1152/ajpendo.00070.2011,PMC3154532,,,"Secretoneurin (SN) is a functional secretogranin II (SgII)-derived peptide that stimulates luteinizing hormone (LH) production and its release in the goldfish. However, the effects of SN on the pituitary of mammalian species and the underlying mechanisms remain poorly understood. To study SN in mammals, we adopted the mouse LβT2 gonadotropin cell line that has characteristics consistent with normal pituitary gonadotrophs. Using radioimmunoassay and real-time RT-PCR, we demonstrated that static treatment with SN induced a significant increment of LH release and production in LβT2 cells in vitro. We found that GnRH increased cellular SgII mRNA level and total SN-immunoreactive protein release into the culture medium. We also report that SN activated the extracellular signal-regulated kinases (ERK) in either 10-min acute stimulation or 3-h chronic treatment. The SN-induced ERK activation was significantly blocked by pharmacological inhibition of MAPK kinase (MEK) with PD-98059 and protein kinase C (PKC) with bisindolylmaleimide. SN also increased the total cyclic adenosine monophosphate (cAMP) levels similarly to GnRH. However, SN did not activate the GnRH receptor. These data indicate that SN activates the protein kinase A (PKA) and cAMP-induced ERK signaling pathways in the LH-secreting mouse LβT2 pituitary cell line.",,"['Zhao, E.', 'McNeilly, Judy R.', 'McNeilly, Alan S.', 'Fischer-Colbrie, Reiner', 'Basak, Ajoy', 'Seong, Jae Young', 'Trudeau, Vance L.']",,,,
,PMC,Expression of chemokine receptor CXCR3 on T cells affects the balance between effector and memory CD8 T-cell generation,http://dx.doi.org/10.1073/pnas.1101881108,PMC3102421,,,"Generation of a robust immunological memory response is essential for protection on subsequent encounters with the same pathogen. The magnitude and quality of the memory CD8 T-cell population are shaped and influenced by the strength and duration of the initial antigenic stimulus as well as by inflammatory cytokines. Although chemokine receptors have been established to play a role in recruitment of effector CD8 T cells to sites of inflammation, their contribution to determination of T-cell fate and shaping of the long-lived memory T-cell population is not fully understood. Here, we investigated whether reduced access to antigen and inflammation through alterations in expression of inflammatory and homeostatic chemokine receptors has an impact on generation of effector and memory CD8 T cells. We found that in mice infected with lymphocytic choriomeningitis virus, colocalization of virus-specific CD8 T cells with antigen in spleen is dependent on expression of the inflammatory chemokine receptor, CXCR3. In addition, absence of CXCR3 expression on CD8 T cells leads to formation of fewer short-lived effector cells and more memory precursor cells. Furthermore, the memory CD8 T-cell population derived from CXCR3-deficient cells has fewer cells of the effector memory phenotype and exhibits a recall response of greater magnitude than that of WT cells. These data demonstrate that CD8 T-cell positioning relative to antigen and inflammatory cytokines in secondary lymphoid organs affects the balance of effector and memory T-cell formation and has both a quantitative and qualitative impact on the long-lived memory CD8 T-cell population.",,"['Hu, Joyce K.', 'Kagari, Takashi', 'Clingan, Jonathan M.', 'Matloubian, Mehrdad']",,,,
,PMC,Chikungunya virus emergence is constrained in Asia by lineage-specific adaptive landscapes,http://dx.doi.org/10.1073/pnas.1018344108,PMC3093459,,,"Adaptation of RNA viruses to a new host or vector species often results in emergence of new viral lineages. However, lineage-specific restrictions on the adaptive processes remain largely unexplored. Recently, a Chikungunya virus (CHIKV) lineage of African origin emerged to cause major epidemics of severe, persistent, debilitating arthralgia in Africa and Asia. Surprisingly, this new lineage is actively replacing endemic strains in Southeast Asia that have been circulating there for 60 y. This replacement process is associated with adaptation of the invasive CHIKV strains to an atypical vector, the Aedes albopictus mosquito that is ubiquitously distributed in the region. Here we demonstrate that lineage-specific epistatic interactions between substitutions at amino acid positions 226 and 98 of the E1 envelope glycoprotein, the latter of which likely resulted from a founder effect, have for 60 y restricted the ability of endemic Asian CHIKV strains to adapt to this new vector. This adaptive constraint appears to be allowing invasion of the unoccupied vector niche by Ae. albopictus-adapted African strains. These results underscore how different adaptive landscapes occupied by closely related viral genotypes can profoundly affect the outcome of viral evolution and disease emergence.",,"['Tsetsarkin, Konstantin A.', 'Chen, Rubing', 'Leal, Grace', 'Forrester, Naomi', 'Higgs, Stephen', 'Huang, Jing', 'Weaver, Scott C.']",,,,
,PMC,Systems Biology in Immunology – A Computational Modeling Perspective,http://dx.doi.org/10.1146/annurev-immunol-030409-101317,PMC3164774,,,"Systems biology is an emerging discipline that combines high-content, multiplexed measurements with informatic and computational modeling methods to better understand biological function at various scales. Here we present a detailed review of the methods used to create computational models and conduct simulations of immune function, We provide descriptions of the key data gathering techniques employed to generate the quantitative and qualitative data required for such modeling and simulation and summarize the progress to date in applying these tools and techniques to questions of immunological interest, including infectious disease. We include comments on what insights modeling can provide that complement information obtained from the more familiar experimental discovery methods used by most investigators and why quantitative methods are needed to eventually produce a better understanding of immune system operation in health and disease.",,"['Germain, Ronald N.', 'Meier-Schellersheim, Martin', 'Nita-Lazar, Aleksandra', 'Fraser, Iain D. C.']",,,,
,PMC,Interference of ribosomal frameshifting by antisense peptide nucleic acids suppresses SARS coronavirus replication,http://dx.doi.org/10.1016/j.antiviral.2011.04.009,PMC4728714,,,"The programmed −1 ribosomal frameshifting (−1 PRF) utilized by eukaryotic RNA viruses plays a crucial role for the controlled, limited synthesis of viral RNA replicase polyproteins required for genome replication. The viral RNA replicase polyproteins of severe acute respiratory syndrome coronavirus (SARS-CoV) are encoded by the two overlapping open reading frames 1a and 1b, which are connected by a −1 PRF signal. We evaluated the antiviral effects of antisense peptide nucleic acids (PNAs) targeting a highly conserved RNA sequence on the – PRF signal. The ribosomal frameshifting was inhibited by the PNA, which bound sequence-specifically a pseudoknot structure in the −1 PRF signal, in cell lines as assessed using a dual luciferase-based reporter plasmid containing the −1 PRF signal. Treatment of cells, which were transfected with a SARS-CoV-replicon expressing firefly luciferase, with the PNA fused to a cell-penetrating peptide (CPP) resulted in suppression of the replication of the SARS-CoV replicon, with a 50% inhibitory concentration of 4.4 μM. There was no induction of type I interferon responses by PNA treatment, suggesting that the effect of PNA is not due to innate immune responses. Our results demonstrate that −1 PRF, critical for SARS-CoV viral replication, can be inhibited by CPP-PNA, providing an effective antisense strategy for blocking −1 PRF signals.",,"['Ahn, Dae-Gyun', 'Lee, Wooseong', 'Choi, Jin-Kyu', 'Kim, Seong-Jun', 'Plant, Ewan P.', 'Almazán, Fernando', 'Taylor, Deborah R.', 'Enjuanes, Luis', 'Oh, Jong-Won']",,,,
,PMC,XMRV as a Human Pathogen?,http://dx.doi.org/10.1016/j.chom.2011.04.001,PMC4551452,,,"XMRV has been proposed to be associated with Prostate Cancer and Chronic Fatigue Syndrome. This proposition has been controversial because many investigators have failed to replicate the reported associations. Here, we explore whether XMRV is an authentic human pathogen in the light of recent findings that indicate otherwise.",,"['Wainberg, Mark A.', 'Jeang, Kuan-Teh']",,,,
,PMC,Molecular Pathways Differentiate Hepatitis C Virus (HCV) Recurrence from Acute Cellular Rejection in HCV Liver Recipients,http://dx.doi.org/10.2119/molmed.2011.00072,PMC3146620,,,"Acute cellular rejection (ACR) and hepatitis C virus (HCV) recurrence (HCVrec) are common complications after liver transplantation (LT) in HCV patients, who share common clinical and histological features, making a differential diagnosis difficult. Fifty-three liver allograft samples from unique HCV LT recipients were studied using microarrays, including a training set (n = 32) and a validation set (n = 19). Two no-HCV-ACR samples from LT recipients were also included. Probe set intensity values were obtained using the robust multiarray average method (RMA) method. Analysis of variance identified statistically differentially expressed genes (P ≤ 0.005). The limma package was used to fit the mixed-effects models using a restricted maximum likelihood procedure. The last absolute shrinkage and selection operator (LASSO) model was fit with HCVrec versus ACR as the dependent variable predicted. N-fold cross-validation was performed to provide an unbiased estimate of generalization error. A total of 179 probe sets were differentially expressed among groups, with 71 exclusive genes between HCVrec and HCV-ACR. No differences were found within ACR group (HCV-ACR vs. no-HCV-ACR). Supervised clustering analysis displayed two clearly independent groups, and no-HCV-ACR clustered within HCV-ACR. HCVrec-related genes were associated with a cytotoxic T-cell profile, and HCV-ACR–related genes were associated with the inflammatory response. The best-fitting LASSO model classifier accuracy, including 15 genes, has an accuracy of 100% in the training set. N-fold cross-validation accuracy was 78.1%, and sensitivity, specificity and positive and negative predictive values were 50.0%, 90.9%, 71.4% and 80.0%, respectively. Arginase type II (ARG2), ethylmalonic encephalopathy 1 (ETHE1), transmembrane protein 176A (TMEM176A) and TMEM176B genes were significantly confirmed in the validation set. A molecular signature capable of distinguishing HCVrec and ACR in HCV LT recipients was identified and validated.",,"['Gehrau, Ricardo', 'Maluf, Daniel', 'Archer, Kellie', 'Stravitz, Richard', 'Suh, Jihee', 'Le, Ngoc', 'Mas, Valeria']",,,,
,PMC,Nrf2 Expression Modifies Influenza A Entry and Replication in Nasal Epithelial Cells,http://dx.doi.org/10.1016/j.freeradbiomed.2011.04.027,PMC3135631,,,"Influenza infection is a major cause of morbidity and mortality worldwide, especially during pandemics outbreaks. Emerging data indicate that phase II antioxidant enzyme pathways could play a role in virus-associated inflammation and immune clearance. While Nrf2-dependent gene expression is known to modify inflammation, a mechanistic role in viral susceptibility and clearance has yet to be elucidated. Therefore, we utilized differentiated human nasal epithelial cells (NEC) and an enzymatic virus-like particle entry assay, to examine the role Nrf2-dependent gene expression has on viral entry and replication. Herein, lentiviral vectors that express Nrf2-specific short hairpin (sh)-RNA effectively decreased both Nrf2 mRNA and Nrf2 protein expression in transduced human NEC from healthy volunteers. Nrf2 knockdown correlated with a significant increase in influenza virus entry and replication. Conversely, supplementation with the potent Nrf2 activators sulforaphane (SFN) and epigallocatechin gallate (EGCG) significantly decreased viral entry and replication. The suppressive effects of EGCG on viral replication were abolished in cells with knocked down Nrf2 expression, suggesting a causal relationship between EGCG-induced activation of Nrf2 and ability to protect against viral infection. Interestingly, the induction of Nrf2 via nutritional supplements SFN and EGCG, increased antiviral mediators/responses; RIG-I, IFN-β, and MxA at baseline in the absence of infection. Our data indicate that there is an inverse relationship between the levels of Nrf2 expression, and viral entry/replication. We also demonstrate that supplementation with Nrf2-activating antioxidants inhibit viral replication in human NEC, which may prove to be an attractive therapeutic intervention. Taken together, these data indicate potential mechanisms by which Nrf2-dependent gene expression regulates susceptibility to influenza in human epithelial cells.",,"['Kesic, Matthew J.', 'Simmons, Steven O.', 'Bauer, Rebecca', 'Jaspers, Ilona']",,,,
,PMC,Materials from peptide assembly: towards the treatment of cancer and transmittable disease,http://dx.doi.org/10.1016/j.cbpa.2011.03.021,PMC3489472,,,"As the prevalence of cancer and transmittable disease persists, the development of new and more advanced therapies remains a priority in medical research. An emerging platform for the treatment of these illnesses is the use of materials formed via peptide assembly where the bulk material itself acts as the therapeutic. Higher ordered peptide structures with defined chemistry are capable of cellular targeting, recognition, and internalization. Recent design efforts are being made to exploit the nanoscale definition of the materials formed by assembling peptides to target cancer and microbial cells and to function as vaccines. This review focuses on assembled peptide materials that actively participate in the biological processes important to cancer and transmittable diseases to exert an anticipated functional outcome.",,"['Branco, Monica C', 'Sigano, Dina M', 'Schneider, Joel P']",,,,
,PMC,SLE with recurrent heart failure and a dermatological clue to another added possibility,http://dx.doi.org/10.1136/bcr.08.2010.3283,PMC3079525,,,"A 36-year-old man with systemic lupus erythematosus (SLE) presented with chest pain, infero-lateral ST segment elevation on ECG and elevation of cardiac biomarkers and inflammatory markers. Coronary angiography ruled out obstructive coronary artery disease (CAD) but echocardiography showed impairment of regional and global left ventricular (LV) function. He was treated for SLE myocarditis but institution of aggressive immunosuppressant therapy only partially improved his condition, which followed a relapsing and remitting course in subsequent months, with progressive impairment of LV function. Cardiac MRI showed active inflammation and extensive transmural scarring. Endomyocardial biopsy (EMB) demonstrated patchy myocardial fibrosis and low-grade myocarditis and PCR assays excluded viral causes. The lack of response to immunosuppression and the detection of the sign of En coup de Sabre were suggestive of scleroderma as the underlying cause of the myocarditis.",,"['Candilio, Luciano', 'D’Cruz, David', 'Perera, Divaka']",,,,
,PMC,Wide Prevalence of Heterosubtypic Broadly Neutralizing Human Anti-Influenza A Antibodies,http://dx.doi.org/10.1093/cid/cir121,PMC3070035,,,"(See the editorial commentary by Donis and Cox, on pages 1010–1012.) Background. Lack of life-long immunity against influenza viruses represents a major global health care problem with profound medical and economic consequences. A greater understanding of the broad-spectrum “heterosubtypic” neutralizing human antibody (BnAb) response to influenza should bring us closer toward a universal influenza vaccine. Methods. Serum samples obtained from 77 volunteers in an H5N1 vaccine study were analyzed for cross-reactive antibodies (Abs) against both subtype hemagglutinins (HAs) and a highly conserved pocket on the HA stem of Group 1 viruses. Cross-reactive Abs in commercial intravenous immunoglobulin were affinity purified using H5-coupled beads followed by step-wise monoclonal antibody competition or acid elution. Enzyme-linked immunosorbent assays were used to quantify cross-binding, and neutralization activity was determined with HA-pseudotyped viruses. Results. Prevaccination serum samples have detectable levels of heterosubtypic HA binding activity to both Group 1 and 2 influenza A viruses, including subtypes H5 and H7, respectively, to which study subjects had not been vaccinated. Two different populations of Broadly neutralizing Abs (BnAbs) were purified from intravenous immunoglobulin by H5 beads: ∼0.01% of total immunoglobulin G can bind to HAs from both Group 1 and 2 and neutralize H1N1 and H5N1 viruses; ∼0.001% is F10-like Abs directed against the HA stem pocket on Group 1 viruses. Conclusion. These data—to our knowledge, for the first time—quantitatively show the presence, albeit at low levels, of two populations of heterosubtypic BnAbs against influenza A in human serum. These observations warrant further investigation to determine their origin, host polymorphism(s) that may affect their expression levels and how to boost these BnAb responses by vaccination to reach sustainable protective levels.",,"['Sui, Jianhua', 'Sheehan, Jared', 'Hwang, William C.', 'Bankston, Laurie A.', 'Burchett, Sandra K.', 'Huang, Chiung-Yu', 'Liddington, Robert C.', 'Beigel, John H.', 'Marasco, Wayne A.']",,,,
,PMC,RATE AND INFLUENCE OF RESPIRATORY VIRUS CO-INFECTION ON PANDEMIC (H1N1) INFLUENZA DISEASE,http://dx.doi.org/10.1016/j.jinf.2011.04.004,PMC3153592,,,"OBJECTIVES: Many patients with influenza have more than one viral agent with co-infection frequencies reported as high as 20%. The impact of respiratory virus copathogens on influenza disease is unclear. We sought to determine if respiratory virus co-infection with pandemic H1N1 altered clinical disease. METHODS: Respiratory samples from 229 and 267 patients identified with and without H1N1 influenza respectively were screened for the presence of 13 seasonal respiratory viruses by multiplex RT-PCR. Disease severity between coinfected and monoinfected H1N1 patients were quantified using a standardized clinical severity scale. Influenza viral load was calculated by quantitative RT-PCR. RESULTS: Thirty (13.1%) influenza samples screened positive for the presence of 31 viral copathogens. The most prominent copathogens included rhinovirus (61.3%), and coronaviruses (16.1%). Median clinical severity of both monoinfected and co-infected groups were 1. Patients coinfected with rhinovirus tended to have lower clinical severity (median 0), whereas non rhinovirus co-infections had substantially higher clinical severity (median 2). No difference in H1N1 viral load was observed between co-infected and mono infected groups. CONCLUSIONS: Respiratory viruses co-infect patients with influenza disease. Patients coinfected with rhinovirus had less severe disease while non-rhinovirus co-infections were associated with substantially higher severity without changes in influenza viral titer.",,"['Esper, Frank P.', 'Spahlinger, Timothy', 'Zhou, Lan']",,,,
,PMC,Gene expression profiling of peripheral blood mononuclear cells from children with active hemophagocytic lymphohistiocytosis,http://dx.doi.org/10.1182/blood-2010-08-300046,PMC3087540,,,"Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, genetically heterogeneous autosomal recessive immune disorder that results when the critical regulatory pathways that mediate immune defense mechanisms and the natural termination of immune/inflammatory responses are disrupted or overwhelmed. To advance the understanding of FHL, we performed gene expression profiling of peripheral blood mononuclear cells from 11 children with untreated FHL. Total RNA was isolated and gene expression levels were determined using microarray analysis. Comparisons between patients with FHL and normal pediatric controls (n = 30) identified 915 down-regulated and 550 up-regulated genes with more than or equal to 2.5-fold difference in expression (P ≤ .05). The expression of genes associated with natural killer cell functions, innate and adaptive immune responses, proapoptotic proteins, and B- and T-cell differentiation were down-regulated in patients with FHL. Genes associated with the canonical pathways of interleukin-6 (IL-6), IL-10 IL-1, IL-8, TREM1, LXR/RXR activation, and PPAR signaling and genes encoding of antiapoptotic proteins were overexpressed in patients with FHL. This first study of genome-wide expression profiling in children with FHL demonstrates the complexity of gene expression patterns, which underlie the immunobiology of FHL.",,"['Sumegi, Janos', 'Barnes, Michael G.', 'Nestheide, Shawnagay V.', 'Molleran-Lee, Susan', 'Villanueva, Joyce', 'Zhang, Kejian', 'Risma, Kimberly A.', 'Grom, Alexei A.', 'Filipovich, Alexandra H.']",,,,
,PMC,Metatranscriptomic analysis of extremely halophilic viral communities,http://dx.doi.org/10.1038/ismej.2011.34,PMC3176508,,,"Hypersaline environments harbour the highest number of viruses reported for aquatic environments. In crystallizer ponds from solar salterns, haloviruses coexist with extremely halophilic Archaea and Bacteria and present a high diversity although little is known about their activity. In this work, we analyzed the viral expression in one crystallizer using a metatranscriptomic approach in which clones from a metaviromic library were immobilized in a microarray and used as probes against total mRNA extracted from the hypersaline community. This approach has two advantages: (i) it overcomes the fact that there is no straightforward, unambiguous way to extract viral mRNA from bulk mRNAs and (ii) it makes the sequencing of all mRNAs unnecessary. Transcriptomic data indicated that the halovirus assemblage was highly active at the time of sampling and the viral groups with the highest expression levels were those related to high GC content haloarchaea and Salinibacter representatives, which are minor components in the environment. Moreover, the changes in the viral expression pattern and in the numbers of free viral particles were analyzed after submitting the samples to two stress conditions: ultraviolet-radiation and dilution. Results showed that Archaea were more sensitive than Bacteria to these stress conditions. The overexpression in the predicted archaeal virus fraction raised and the total numbers of free viruses increased. Furthermore, we identified some very closely related viral clones, displaying single-nucleotide polymorphisms, which were expressed only under certain conditions. These clones could be part of very closely related virus genomes for which we propose the term ‘ecoviriotypes'.",,"['Santos, Fernando', 'Moreno-Paz, Mercedes', 'Meseguer, Inmaculada', 'López, Cristina', 'Rosselló-Mora, Ramon', 'Parro, Víctor', 'Antón, Josefa']",,,,
,PMC,Depression after Exposure to Stressful Events: Lessons Learned from the SARS Epidemic,http://dx.doi.org/10.1016/j.comppsych.2011.02.003,PMC3176950,,,"AIM: To examine, among hospital employees exposed to an outbreak of severe acute respiratory syndrome (SARS), post-outbreak levels of depressive symptoms, and the relationship between those depressive symptom levels and the types of outbreak event exposures experienced. METHODS: In 2006, randomly selected employees (n = 549) of a hospital in Beijing were surveyed concerning their exposures to the city’s 2003 SARS outbreak, and the ways in which the outbreak had affected their mental health. Subjects were assessed on sociodemographic factors, on types of exposure to the outbreak, and on symptoms of post-traumatic stress disorder (PTSD) and depression. RESULTS: The results of multinomial regression analyses showed that, with other relevant factors controlled for, being single, having been quarantined during the outbreak, having been exposed to other traumatic events prior to SARS, and perceived SARS-related risk level during the outbreak were found to increase the odds of having a high level of depressive symptoms three years later. Altruistic acceptance of risk during the outbreak was found to decrease the odds of high post-outbreak depressive symptom levels. CONCLUSIONS: Policy makers and mental health professionals working to prepare for potential disease outbreaks should be aware that the experience of being quarantined can, in some cases, lead to long-term adverse mental health consequences.",,"['Liu, Xinhua', 'Kakade, Meghana', 'Fuller, Cordelia J.', 'Fan, Bin', 'Fang, Yunyun', 'Kong, Junhui', 'Guan, Zhiqiang', 'Wu, Ping']",,,,
,PMC,ACRT‐AFMR‐SCTS annual meeting abstracts,http://dx.doi.org/10.1111/j.1752-8062.2011.00269.x,PMC5439735,,,,,,,,,
,PMC,Sensitive detection of nucleic acids by PNA hybridization directed co-localization of fluorescent beads,http://dx.doi.org/10.4161/adna.2.2.16562,PMC3166491,,,"We have designed a pair of biotinylated peptide nucleic acid (PNA) probes targeting two sequences in 18S rRNA (from the parasite Trypanosoma brucei) at a distance of 191 nt (corresponding to maximum distance of ca. 60 nm) from each other. The PNA probes were individually bound to (strept)avidin-coated fluorescent beads, differing in size and color [green beads (1 µm) and red beads (5.9 µm)], thereby allowing distinct detection of each PNA probe by conventional fluorescence microscopy. These two PNA beads showed easily detectable co-localization when simultaneously hybridizing to a target nucleic acid. The assay detected the parasite 18S rRNA down to 1.6 fmol while there was no such co-localization visible with human 18S rRNA not containing the PNA targets. Furthermore, the assay showed positive detection with 1.6 ng of total RNA (corresponding to RNA from ca. 300 parasites). Upon further optimization this method may provide a new tool for a diagnosis of Human African Trypanosomiasis (HAT) and it may more generally have applications within diagnostics for (neglected) infectious diseases.",,"['Shiraishi, Takehiko', 'Deborggraeve, Stijn', 'Büscher, Philippe', 'Nielsen, Peter E']",,,,
,PMC,Characterization of Selective Ubiquitin and Ubiquitin-Like Protease Inhibitors Using a Fluorescence-Based Multiplex Assay Format,http://dx.doi.org/10.1089/adt.2010.0317,PMC3065724,,,"The reversible conjugation of ubiquitin and ubiquitin-like (UbL) proteins to protein substrates plays a critical role in the regulation of many cellular pathways. The removal of ubiquitin from target proteins is performed by ubiquitin proteases also known as deubiquitylases (DUBs). Owing to their substrate specificity and the central role ubiquitylation plays in cell signaling pathways, DUB are attractive targets for therapeutic development. The development of DUB inhibitors requires assays that are amenable to high-throughput screening and provide rapid assessment of inhibitor selectivity. Determination of inhibitor selectivity at an early stage of drug discovery will reduce drug failure in the clinic as well as reduce overall drug development costs. We have developed two novel assays, UbL-Enterokinase light chain and UbL-Granzyme B, for quantifying ubiquitin and UbL protease activity. In our quest to discover and characterize novel chemical entities, we have combined these assays with a previously developed assay in a multiplex format. This multiplex format allows for the detection of three distinct protease activities simultaneously, in a single well. We have demonstrated that the multiplex format is able to distinguish between selective and nonselective protease inhibitors. Specifically, we have used this assay format to characterize P022077, a selective ubiquitin-specific protease 7 inhibitor discovered at Progenra.",,"['Tian, Xufan', 'Isamiddinova, Nigora S.', 'Peroutka, Raymond J.', 'Goldenberg, Seth J.', 'Mattern, Michael R.', 'Nicholson, Benjamin', 'Leach, Craig']",,,,
,PMC,A High-Throughput Screening Strategy to Overcome Virus Instability,http://dx.doi.org/10.1089/adt.2010.0298,PMC3065722,,,"Respiratory syncytial virus (RSV) is a widely distributed pathogen that causes severe disease in children, the elderly, and immunocompromised individuals. Both vaccine development and drug discovery have been hampered by the inherent instability of the virus itself. Drug discovery efforts have had limited success due, at least in part, to the lack of an antiviral assay robust enough for high-throughput screening. Instability of the purified virus has long been recognized as a problem in RSV research and has been a major hurdle to producing a virus-based screening assay. Using frozen RSV-infected cells as the source of infectious material, we have overcome the problem of virus instability and validated a cell-based high-throughput screening assay to screen for inhibitors of RSV-induced cytopathic effect. The assay was validated with 1,280 compounds identified as potentially active against RSV (Long strain) in a virus-based screen. To date over 300,000 compounds have been screened over several months with minimal variability in cell or virus controls. Long-term assay stability studies are still in progress.",,"['Rasmussen, Lynn', 'Maddox, Clinton', 'Moore, Blake P.', 'Severson, William', 'White, E. Lucile']",,,,
,PMC,"Crohn disease: A current perspective on genetics, autophagy and immunity",http://dx.doi.org/10.4161/auto.7.4.13074,PMC3842289,,,"Crohn disease (CD) is a chronic and debilitating inflammatory condition of the gastrointestinal tract.(1) Prevalence in western populations is 100–150/100,000 and somewhat higher in Ashkenazi Jews. Peak incidence is in early adult life, although any age can be affected and a majority of affected individuals progress to relapsing and chronic disease. Medical treatments rely significantly on empirical corticosteroid therapy and immunosuppression, and intestinal resectional surgery is frequently required. Thus, 80% of patients with CD come to surgery for refractory disease or complications. It is hoped that an improved understanding of pathogenic mechanisms, for example by studying the genetic basis of CD and other forms of inflammatory bowel diseases (IBD), will lead to improved therapies and possibly preventative strategies in individuals identified as being at risk.",,"['Stappenbeck, Thaddeus S.', 'Rioux, John D.', 'Mizoguchi, Atsushi', 'Saitoh, Tatsuya', 'Huett, Alan', 'Darfeuille-Michaud, Arlette', 'Wileman, Tom', 'Mizushima, Noboru', 'Carding, Simon', 'Akira, Shizuo', 'Parkes, Miles', 'Xavier, Ramnik J.']",,,,
,PMC,Unusual central nervous system lesions in slaughter-weight pigs with porcine circovirus type 2 systemic infection,,PMC3058650,,,Porcine circovirus type 2 systemic infection was diagnosed in 2 slaughter-weight pigs based on postmortem examination. The infection was associated with unusual central nervous system lesions characterized by a multifocal lymphohistiocytic to granulomatous meningoencephalomyelitis with giant cell formation. The role of these nervous system lesions in the development of the clinical signs in these pigs remains uncertain.,,"['Drolet, Richard', 'Cardinal, François', 'Houde, Alain', 'Gagnon, Carl A.']",,,,
,PMC,Integrated Multilevel Surveillance of the World's Infecting Microbes and Their Resistance to Antimicrobial Agents,http://dx.doi.org/10.1128/CMR.00021-10,PMC3122493,,,"Summary: Microbial surveillance systems have varied in their source of support; type of laboratory reporting (patient care or reference); inclusiveness of reports filed; extent of microbial typing; whether single hospital, multihospital, or multicountry; proportion of total medical centers participating; and types, levels, integration across levels, and automation of analyses performed. These surveillance systems variably support the diagnosis and treatment of patients, local or regional infection control, local or national policies and guidelines, laboratory capacity building, sentinel surveillance, and patient safety. Overall, however, only a small fraction of available data are under any surveillance, and very few data are fully integrated and analyzed. Advancing informatics and genomics can make microbial surveillance far more efficient and effective at preventing infections and improving their outcomes. The world's microbiology laboratories should upload their reports each day to programs that detect events, trends, and epidemics in communities, hospitals, countries, and the world.",,"[""O'Brien, Thomas F."", 'Stelling, John']",,,,
,PMC,Efficacy of the Canine Influenza Virus H3N8 Vaccine To Decrease Severity of Clinical Disease after Cochallenge with Canine Influenza Virus and Streptococcus equi subsp. zooepidemicus,http://dx.doi.org/10.1128/CVI.00500-10,PMC3122572,,,"Since first emerging in the North American canine population in 2004, canine influenza virus (CIV) subtype H3N8 has shown horizontal transmission among dogs, with a high level of adaptation to this species. The severity of disease is variable, and coinfection by other respiratory pathogens is an important factor in the degree of morbidity and mortality. The first influenza vaccine for dogs, an inactivated vaccine containing CIV subtype H3N8, was conditionally approved by the U.S. Department of Agriculture (USDA) for licensure in May 2009 and fully licensed in June 2010. This study evaluates the efficacy of this vaccine to reduce the severity of illness in dogs cochallenged with virulent CIV and Streptococcus equi subsp. zooepidemicus.",,"['Larson, Laurie J.', 'Henningson, Jamie', 'Sharp, Patricia', 'Thiel, Bliss', 'Deshpande, Muralidhar S.', 'Davis, Tamara', 'Jayappa, Huchappa', 'Wasmoen, Terri', 'Lakshmanan, Nallakannu', 'Schultz, Ronald D.']",,,,
,PMC,Knocking out Angiotensin II in the Heart,http://dx.doi.org/10.1007/s11906-011-0180-4,PMC3278322,,,"Despite ongoing medical advances, cardiovascular disease continues to be a leading health concern. The renin-angiotensin system (RAS) plays an important role in regulating cardiovascular function, and is, therefore, the subject of extensive study. Several of the drugs currently used to treat hypertension and heart failure are designed to target Ang II synthesis and function, but none have been able to completely block the effects of RAS signaling thus far. This review discusses current and emerging approaches towards inhibiting cardiac RAS function in order to further improve cardiovascular disease outcomes.",,"['Zablocki, Daniela', 'Sadoshima, Junichi']",,,,
,PMC,Mycoplasma pneumoniae respiratory tract infections among Greek children,,PMC3209678,,,"Background: M. pneumoniae is a common cause of respiratory tract infections (RTIs) of variable severity especially in children. New diagnostic techniques offered more reliable information about the epidemiology of infection by this pathogen. Aim: The aim of this study was to investigate the prevalence and epidemiology of acute M. pneumoniae infections among Greek children hospitalized for RTIs using more advanced techniques. Material and Methods: The study included 225 Greek children hospitalized for RTIs during a 15-month period. Throat swab specimens were tested by PCR for the detection of M. pneumoniae, while IgG and IgM antibodies were determined by ELISA and, in certain cases, also by western-blot. In parallel, specimens were tested for the presence of additional respiratory pathogens. Results: M. pneumoniae infection was diagnosed as the only pathogen in 25 (11.1%) cases, being the second (after respiratory syncytial virus- RSV) most often detected pathogen. The proportion of cases with M. pneumoniae infection in age group 8-14 years (23.3%) was significantly higher than that in <3 years age group. Conclusion: During our study period, M. pneumoniae was the second causative agent of RTIs after RSV. The proportion of children with M. pneumoniae RTIs increased with age, while most cases were reported during summer and autumn.",,"['Almasri, M', 'Diza, E', 'Papa, A', 'Eboriadou, M', 'Souliou, E']",,,,
,PMC,Potential targets for pancreatic cancer immunotherapeutics,http://dx.doi.org/10.2217/imt.11.10,PMC3148788,,,"Pancreatic adenocarcinoma is the fourth leading cause of cancer death with an overall 5-year survival of less than 5%. As there is ample evidence that pancreatic adenocarcinomas elicit antitumor immune responses, identification of pancreatic cancer-associated antigens has spurred the development of vaccination-based strategies for treatment. While promising results have been observed in animal tumor models, most clinical studies have found only limited success. As most trials were performed in patients with advanced pancreatic cancer, the contribution of immune suppressor mechanisms should be taken into account. In this article, we detail recent work in tumor antigen vaccination and the recently identified mechanisms of immune suppression in pancreatic cancer. We offer our perspective on how to increase the clinical efficacy of vaccines for pancreatic cancer.",,"['Dodson, Lindzy F', 'Hawkins, William G', 'Goedegebuure, Peter']",,,,
,PMC,"Prediction of outcome and prognosis of patients on mechanical ventilation using body mass index, SOFA score, C-Reactive protein, and serum albumin",http://dx.doi.org/10.4103/0972-5229.83011,PMC3145309,21814371,CC BY-NC-SA,"CONTEXT: Body mass index (BMI), serum albumin, and C-reactive protein (CRP) appear to be major determinants of hospitalization. AIM: To determine the predictive ability of BMI, Sequential Organ Failure Assessment (SOFA score), serum albumin, and CRP to assess the duration and outcome of mechanical ventilation (MV). MATERIALS AND METHODS: Thirty patients aged >18 years who required mechanical ventilation (MV) were enrolled for the study. They were divided into two groups; patients who improved (Group 1), patients who expired (Group 2). Group 1 was further divided into two groups: patients on MV for <5 days (Group A), and patients on MV for >5days (Group B). BMI and SOFA score were calculated, and serum albumin and CRP were estimated. RESULTS AND DISCUSSION: Out of the 30 patients, 18 patients successfully improved after MV (Group 1) and 12 patients expired (Group 2). Among the 18 patients in group 1, ten patients improved within 5 days (Group A) and 8 patients after 5 days (Group B). SOFA score and CRP were significantly increased (P value 0.0003 and 0.0001, respectively) in group 2 when compared to group 1. CRP >24.2 mg/L or SOFA score >7 at the start of MV increases the probability of mortality by factor 13.08 or 3.92, respectively The above parameters did not show any statistical difference when group A was compared to group B. CONCLUSION: Simple, economic and easily accessible markers like CRP and assessment tools of critically ill patients with SOFA score are important determinants of possible outcomes of a patient from MV.",2011 Apr-Jun,"['Bhattacharya, Barnamoy', 'Prashant, Akila', 'Vishwanath, Prashant', 'Suma, M. N.', 'Nataraj, B.']",Indian J Crit Care Med,,,
,PMC,High Mannose-binding Lectin with Preference for the Cluster of α1–2-Mannose from the Green Alga Boodlea coacta Is a Potent Entry Inhibitor of HIV-1 and Influenza Viruses,http://dx.doi.org/10.1074/jbc.M110.216655,PMC3103324,,,"The complete amino acid sequence of a lectin from the green alga Boodlea coacta (BCA), which was determined by a combination of Edman degradation of its peptide fragments and cDNA cloning, revealed the following: 1) B. coacta used a noncanonical genetic code (where TAA and TAG codons encode glutamine rather than a translation termination), and 2) BCA consisted of three internal tandem-repeated domains, each of which contains the sequence motif similar to the carbohydrate-binding site of Galanthus nivalis agglutinin-related lectins. Carbohydrate binding specificity of BCA was examined by a centrifugal ultrafiltration-HPLC assay using 42 pyridylaminated oligosaccharides. BCA bound to high mannose-type N-glycans but not to the complex-type, hybrid-type core structure of N-glycans or oligosaccharides from glycolipids. This lectin had exclusive specificity for α1–2-linked mannose at the nonreducing terminus. The binding activity was enhanced as the number of terminal α1–2-linked mannose substitutions increased. Mannobiose, mannotriose, and mannopentaose were incapable of binding to BCA. Thus, BCA preferentially recognized the nonreducing terminal α1–2-mannose cluster as a primary target. As predicted from carbohydrate-binding propensity, this lectin inhibited the HIV-1 entry into the host cells at a half-maximal effective concentration of 8.2 nm. A high association constant (3.71 × 10(8) m(−1)) of BCA with the HIV envelope glycoprotein gp120 was demonstrated by surface plasmon resonance analysis. Moreover, BCA showed the potent anti-influenza activity by directly binding to viral envelope hemagglutinin against various strains, including a clinical isolate of pandemic H1N1-2009 virus, revealing its potential as an antiviral reagent.",,"['Sato, Yuichiro', 'Hirayama, Makoto', 'Morimoto, Kinjiro', 'Yamamoto, Naoki', 'Okuyama, Satomi', 'Hori, Kanji']",,,,
,PMC,Evaluation of Twelve Real-Time Reverse Transcriptase PCR Primer-Probe Sets for Detection of Pandemic Influenza A/H1N1 2009 Virus,http://dx.doi.org/10.1128/JCM.01914-10,PMC3122877,,,"Real-time reverse transcriptase PCR (rRT-PCR) assays have greatly contributed to the detection, control, and prevention of the pandemic influenza A/H1N1 2009 virus. To improve the rRT-PCR assays for detection of pandemic influenza A/H1N1 2009 virus, we evaluated the sensitivity, specificity, and performance of 12 rRT-PCR primer-probe sets [SW (a) to SW (l)] using a panel of virus strains and clinical specimens. These primer-probe sets were derived from published work and designed for detecting the hemagglutinin (HA) or the neuraminidase (NA) gene of the pandemic influenza A/H1N1 2009 virus. A primer-probe set, SW (CDC), developed by the Centers for Disease Control and Prevention (U.S. CDC) to target the HA gene of pandemic influenza A/H1N1 2009 virus, was used as a referee method. Our results demonstrated that although all primer-probe sets in this study had as high as 98.4 to 100% in silico coverage, some of the primer-probe sets had better specificity, sensitivity, and amplification efficiency than others. Two primer-probe sets, SW (h) and SW (l), which target the NA gene of pandemic influenza A/H1N1 2009 virus, were highly sensitive (10(4) copies/reaction), had high detection rates (56/60, P = 0.134, and 59/60, P = 1.000), and showed ideal specificity compared with SW (CDC). In addition, a cocktail of primer-probe sets targeted to the HA and NA genes displayed higher detection sensitivity than primer-probe sets targeting HA or NA alone, indicating that for practical applications, a combination of primer-probes targeting HA and NA genes is the best option for the detection of pandemic influenza A/H1N1 2009 virus.",,"['Yang, Yaowu', 'Huang, Fang', 'Gonzalez, Richard', 'Wang, Wei', 'Lu, Guilan', 'Li, Yongjun', 'Vernet, Guy', 'Jin, Qi', 'Wang, Jianwei']",,,,
,PMC,"Laboratory Diagnosis, Epidemiology, and Clinical Outcomes of Pandemic Influenza A and Community Respiratory Viral Infections in Southern Brazil",http://dx.doi.org/10.1128/JCM.02205-10,PMC3122811,,,"Community respiratory viruses (CRVs) are commonly associated with seasonal infections. They have been associated with higher morbidity and mortality among children, elderly individuals, and immunosuppressed patients. In April 2009, the circulation of a new influenza A virus (FLUA H1N1v) was responsible for the first influenza pandemic of this century. We report the clinical and epidemiological profiles of inpatients infected with CRVs or with FLUA H1N1v at a tertiary care hospital in southern Brazil. In addition, we used these profiles to evaluate survivor and nonsurvivor patients infected with FLUA H1N1v. Multiplex reverse transcription-PCR (RT-PCR) and real time RT-PCR were used to detect viruses in inpatients with respiratory infections. Record data from all patients were reviewed. A total of 171 patients were examined over a period of 16 weeks. Of these, 39% were positive for FLUA H1N1v, 36% were positive for CRVs, and 25% were negative. For the FLUA H1N1v- and CRV-infected patients, epidemiological data regarding median age (30 and 1.5 years), myalgia (44% and 13%), need for mechanical ventilation (44% and 9%), and mortality (35% and 9%) were statistically different. In a multivariate analysis comparing survivor and nonsurvivor patients infected with influenza A virus H1N1, median age and creatine phosphokinase levels were significantly associated with a severe outcome. Seasonal respiratory infections are a continuing concern. Our results highlight the importance of studies on the prevalence and severity of these infections and that investments in programs of clinical and laboratory monitoring are essential to detect the appearance of new infective agents.",,"['Raboni, Sonia M.', 'Stella, Vanessa', 'Cruz, Cristina R.', 'França, João B.', 'Moreira, Suzana', 'Gonçalves, Lili', 'Nogueira, Meri B.', 'Vidal, Luine R.', 'Almeida, Sergio M.', 'Debur, Maria C.', 'Carraro, Hipolito', 'Duarte dos Santos, Claudia N.']",,,,
,PMC,Detection of Hemagglutinin Variants of the Pandemic Influenza A (H1N1) 2009 Virus by Pyrosequencing,http://dx.doi.org/10.1128/JCM.02424-10,PMC3122807,,,"For influenza viruses, pyrosequencing has been successfully applied to the high-throughput detection of resistance markers in genes encoding the drug-targeted M2 protein and neuraminidase. In this study, we expanded the utility of this assay to the detection of multiple receptor binding variants of the hemagglutinin protein of influenza viruses directly in clinical specimens. Specifically, a customized pyrosequencing protocol that permits detection of virus variants with the D, G, N, or E amino acid at position 222 in the hemagglutinin of the 2009 pandemic influenza A (H1N1) virus was developed. This customized pyrosequencing protocol was applied to the analysis of 241 clinical specimens. The use of the optimized nucleotide dispensation order allowed detection of mixtures of variants in 10 samples (4.1%) which the standard cyclic nucleotide dispensation protocol failed to detect. The optimized pyrosequencing protocol is expected to provide a more accurate tool in the analysis of virus variant composition.",,"['Levine, Marnie', 'Sheu, Tiffany G.', 'Gubareva, Larisa V.', 'Mishin, Vasiliy P.']",,,,
,PMC,Utility of a Panviral Microarray for Detection of Swine Respiratory Viruses in Clinical Samples,http://dx.doi.org/10.1128/JCM.01876-10,PMC3122799,,,"Several factors have recently converged, elevating the need for highly parallel diagnostic platforms that have the ability to detect many known, novel, and emerging pathogenic agents simultaneously. Panviral DNA microarrays represent the most robust approach for massively parallel viral surveillance and detection. The Virochip is a panviral DNA microarray that is capable of detecting all known viruses, as well as novel viruses related to known viral families, in a single assay and has been used to successfully identify known and novel viral agents in clinical human specimens. However, the usefulness and the sensitivity of the Virochip platform have not been tested on a set of clinical veterinary specimens with the high degree of genetic variance that is frequently observed with swine virus field isolates. In this report, we investigate the utility and sensitivity of the Virochip to positively detect swine viruses in both cell culture-derived samples and clinical swine samples. The Virochip successfully detected porcine reproductive and respiratory syndrome virus (PRRSV) in serum containing 6.10 × 10(2) viral copies per microliter and influenza A virus in lung lavage fluid containing 2.08 × 10(6) viral copies per microliter. The Virochip also successfully detected porcine circovirus type 2 (PCV2) in serum containing 2.50 × 10(8) viral copies per microliter and porcine respiratory coronavirus (PRCV) in turbinate tissue homogenate. Collectively, the data in this report demonstrate that the Virochip can successfully detect pathogenic viruses frequently found in swine in a variety of solid and liquid specimens, such as turbinate tissue homogenate and lung lavage fluid, as well as antemortem samples, such as serum.",,"['Nicholson, Tracy L.', 'Kukielka, Deborah', 'Vincent, Amy L.', 'Brockmeier, Susan L.', 'Miller, Laura C.', 'Faaberg, Kay S.']",,,,
,PMC,The advent of ECMO and pumpless extracorporeal lung assist in ARDS,http://dx.doi.org/10.4103/0974-2700.82212,PMC3132365,21769212,CC BY-NC-SA,"Despite advances in critical care facilities and ventilation therapies acute respiratory distress syndrome (ARDS) is associated with high mortality rates. The condition can stem from a multitude of causes including pneumonia, septicemia and trauma ultimately resulting in ARDS. ARDS is characterized by respiratory insufficiency with severe hypoxemia or hypercapnia. The treatment strategy depends on the knowledge of the underlying disease. But lung-protective ventilation with adjusted positive end-expiratory pressure remains the most effective therapeutic tool despite advances in prone positioning, inhalation of nitric oxide and the use of steroids. Newer modalities including extracorporeal membrane oxygenation (ECMO) and pumpless extracorporeal lung assist (PECLA) are being increasingly introduced in critical care settings as rescue therapies in patients who fail to respond to conservative measures. We describe here the introduction and advances of both ECMO and PECLA in the management of ARDS.",2011 Apr-Jun,"['Hamid, I A', 'Hariharan, A S', 'Shankar, N R Ravi']",J Emerg Trauma Shock,,,
,PMC,Investigation of Primary Cilia in the Pathogenesis of Biliary Atresia,http://dx.doi.org/10.1097/MPG.0b013e318200eb6f,PMC4085747,,,,,"['Hartley, Jane L.', ""O'Callaghan, Christopher"", 'Rossetti, Sandro', 'Consugar, Mark', 'Ward, Christopher J.', 'Kelly, Deirdre A.', 'Harris, Peter C.']",,,,
,PMC,TRIM56 Is a Virus- and Interferon-Inducible E3 Ubiquitin Ligase That Restricts Pestivirus Infection,http://dx.doi.org/10.1128/JVI.02546-10,PMC3126137,,,"The tripartite motif (TRIM) protein family comprises more than 60 members that have diverse functions in various biological processes. Although a small number of TRIM proteins have been shown to regulate innate immunity, much remains to be learned about the functions of the majority of the TRIM proteins. Here we identify TRIM56 as a cellular protein associated with the N-terminal protease (N(pro)) of bovine viral diarrhea virus (BVDV), a pestiviral interferon antagonist which degrades interferon regulatory factor 3 (IRF3) through the proteasome. We found that TRIM56 was constitutively expressed in most tissues, and its abundance was further upregulated moderately by interferon or virus. The manipulation of TRIM56 abundance did not affect the protein turnover of N(pro) and IRF3. Rather, ectopic expression of TRIM56 substantially impaired, while knockdown of TRIM56 expression greatly enhanced, BVDV replication in cell culture. The antiviral activity of TRIM56 depended on its E3 ubiquitin ligase activity as well as the integrity of its C-terminal region but was not attributed to a general augmentation of the interferon antiviral response. Overexpression of TRIM56 did not inhibit the replication of vesicular stomatitis virus or hepatitis C virus, a virus closely related to BVDV. Together, our data demonstrate that TRIM56 is a novel antiviral host factor that restricts pestivirus infection.",,"['Wang, Jie', 'Liu, Baoming', 'Wang, Nan', 'Lee, Young-Min', 'Liu, Chunming', 'Li, Kui']",,,,
,PMC,The Leader Proteinase of Foot-and-Mouth Disease Virus Negatively Regulates the Type I Interferon Pathway by Acting as a Viral Deubiquitinase,http://dx.doi.org/10.1128/JVI.02589-10,PMC3126127,,,"The leader proteinase (L(pro)) of foot-and-mouth disease virus (FMDV) is a papain-like proteinase that plays an important role in FMDV pathogenesis. Previously, it has been shown that L(pro) is involved in the inhibition of the type I interferon (IFN) response by FMDV. However, the underlying mechanisms remain unclear. Here we demonstrate that FMDV Lb(pro), a shorter form of L(pro), has deubiquitinating activity. Sequence alignment and structural bioinformatics analyses revealed that the catalytic residues (Cys51 and His148) are highly conserved in FMDV Lb(pro) of all seven serotypes and that the topology of FMDV Lb(pro) is remarkably similar to that of ubiquitin-specific protease 14 (USP14), a cellular deubiquitylation enzyme (DUB), and to that of severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLpro), a coronaviral DUB. Both purified Lb(pro) protein and in vivo ectopically expressed Lb(pro) removed ubiquitin (Ub) moieties from cellular substrates, acting on both lysine-48- and lysine-63-linked polyubiquitin chains. Furthermore, Lb(pro) significantly inhibited ubiquitination of retinoic acid-inducible gene I (RIG-I), TANK-binding kinase 1 (TBK1), TNF receptor-associated factor 6 (TRAF6), and TRAF3, key signaling molecules in activation of type I IFN response. Mutations in Lb(pro) that ablate the catalytic activity (C51A or D163N/D164N) or disrupt the SAP (for SAF-A/B, Acinus, and PIAS) domain (I83A/L86A) abrogated the DUB activity of Lb(pro) as well as its ability to block signaling to the IFN-β promoter. Collectively, these results demonstrate that FMDV Lb(pro) possesses DUB activity in addition to serving as a viral proteinase and describe a novel mechanism evolved by FMDV to counteract host innate antiviral responses.",,"['Wang, Dang', 'Fang, Liurong', 'Li, Ping', 'Sun, Li', 'Fan, Jinxiu', 'Zhang, Qingye', 'Luo, Rui', 'Liu, Xiangtao', 'Li, Kui', 'Chen, Huanchun', 'Chen, Zhongbin', 'Xiao, Shaobo']",,,,
,PMC,Epithelial Cells Lining Salivary Gland Ducts Are Early Target Cells of Severe Acute Respiratory Syndrome Coronavirus Infection in the Upper Respiratory Tracts of Rhesus Macaques,http://dx.doi.org/10.1128/JVI.02292-10,PMC3126125,,,"The shedding of severe acute respiratory syndrome coronavirus (SARS-CoV) into saliva droplets plays a critical role in viral transmission. The source of high viral loads in saliva, however, remains elusive. Here we investigate the early target cells of infection in the entire array of respiratory tissues in Chinese macaques after intranasal inoculations with a single-cycle pseudotyped virus and a pathogenic SARS-CoV. We found that angiotensin-converting enzyme 2-positive (ACE2(+)) cells were widely distributed in the upper respiratory tract, and ACE2(+) epithelial cells lining salivary gland ducts were the early target cells productively infected. Our findings also have implications for SARS-CoV early diagnosis and prevention.",,"['Liu, Li', 'Wei, Qiang', 'Alvarez, Xavier', 'Wang, Haibo', 'Du, Yanhua', 'Zhu, Hua', 'Jiang, Hong', 'Zhou, Jingying', 'Lam, Pokman', 'Zhang, Linqi', 'Lackner, Andrew', 'Qin, Chuan', 'Chen, Zhiwei']",,,,
,PMC,Authors’ reply,,PMC3109845,21712933,CC BY,,2011 Apr-Jun,"['Mohapatra, Prasanta R.', 'Dutt, Naveen', 'Khanduri, Sushant', 'Mishra, Baijayantimala', 'Janmeja, Ashok K.']",Lung India,,,
,PMC,Noninvasive ventilation in acute respiratory failure due to H1N1 influenza: A word of caution,http://dx.doi.org/10.4103/0970-2113.80340,PMC3109844,21712932,CC BY,,2011 Apr-Jun,"['Singh, Akashdeep', 'Singh, Jaspreet']",Lung India,,,
,PMC,Genome-virome interactions: examining the role of common viral infections in complex disease,http://dx.doi.org/10.1038/nrmicro2541,PMC3678363,,,"New technologies have widened our view of “complex diseases”--diseases with both genetic and environmental risk factors. Here, we explore recent genetic and virologic evidence implicating host-virus interactions in three diseases—type 1 diabetes, inflammatory bowel disease, and asthma. In these examples, the viruses implicated in disease are mucosal infections that affect most of the population and that are asymptomatic or mild in many hosts. These findings place a new emphasis on common viral infections as an important environmental factor in complex disease pathogenesis, and they compel us to pursue a better understanding of host interactions with the human virome.",,"['Foxman, Ellen F.', 'Iwasaki, Akiko']",,,,
,PMC,CHLAMYDIA PERSISTENCE – A TOOL TO DISSECT CHLAMYDIA-HOST INTERACTIONS,http://dx.doi.org/10.1016/j.micinf.2011.03.004,PMC3636554,,,"Under stress, chlamydiae can enter a non-infectious but viable state termed persistence. In the absence of a tractable genetic system, persistence induction provides an important experimental tool with which to study these fascinating organisms. This review will discuss examples of: i) persistence studies that have illuminated critical chlamydiae/host interactions; and ii) novel persistence models that will do so in the future.",,"Schoborg, R.V.",,,,
,PMC,Roles for Biological Membranes in Regulating Human Immunodeficiency Virus Replication and Progress in the Development of HIV Therapeutics that Target Lipid Metabolism,http://dx.doi.org/10.1007/s11481-011-9274-7,PMC3417146,,,"Infection by the human immunodeficiency virus (HIV) involves a number of important interactions with lipid components in host membranes that regulate binding, fusion, internalization, and viral assembly. Available data suggests that HIV actively modifies the sphingolipid content of cellular membranes to create focal environments that are favorable for infection. In this review, we summarize the roles that membrane lipids play in HIV infection and discuss the current status of therapeutics that attempt to modify biological membranes to inhibit HIV.",,"['Haughey, Norman J.', 'Tovar-y-Romo, Luis B.', 'Bandaru, Veera Venkata Ratnam']",,,,
,PMC,Adaptive human behavior in epidemiological models,http://dx.doi.org/10.1073/pnas.1011250108,PMC3076845,,,"The science and management of infectious disease are entering a new stage. Increasingly public policy to manage epidemics focuses on motivating people, through social distancing policies, to alter their behavior to reduce contacts and reduce public disease risk. Person-to-person contacts drive human disease dynamics. People value such contacts and are willing to accept some disease risk to gain contact-related benefits. The cost–benefit trade-offs that shape contact behavior, and hence the course of epidemics, are often only implicitly incorporated in epidemiological models. This approach creates difficulty in parsing out the effects of adaptive behavior. We use an epidemiological–economic model of disease dynamics to explicitly model the trade-offs that drive person-to-person contact decisions. Results indicate that including adaptive human behavior significantly changes the predicted course of epidemics and that this inclusion has implications for parameter estimation and interpretation and for the development of social distancing policies. Acknowledging adaptive behavior requires a shift in thinking about epidemiological processes and parameters.",,"['Fenichel, Eli P.', 'Castillo-Chavez, Carlos', 'Ceddia, M. G.', 'Chowell, Gerardo', 'Parra, Paula A. Gonzalez', 'Hickling, Graham J.', 'Holloway, Garth', 'Horan, Richard', 'Morin, Benjamin', 'Perrings, Charles', 'Springborn, Michael', 'Velazquez, Leticia', 'Villalobos, Cristina']",,,,
,PMC,Acute Allograft Rejection: Cellular and Humoral Processes,http://dx.doi.org/10.1016/j.ccm.2011.02.008,PMC3089893,,,"Acute cellular rejection affects greater than a third of lung transplant recipients. Alloreactive T lymphocytes, responding directly or indirectly to donor antigen, constitute the basis of lung allograft rejection, as diagnosed by well-established histopathological criteria that reflect the severity of perivascular or peribronchial inflammation in the lung allograft. Recent evidence supports a more complex immune response to the allograft with involvement of humoral mechanisms, characterized by circulating antibody to donor HLA and specific patterns of lung injury, occurring in parallel with T cell-based rejection. Emerging evidence further suggests that the interaction between recipient genetics, immunosuppression therapies, and allograft environmental exposures, including pulmonary infection, contributes to high rejection rates after lung transplantation. A greater understanding of the heterogeneous mechanisms of lung rejection is critical to developing effective therapies that target the precise pathophysiology of the disease and ultimately improve long-term lung transplant outcomes.",,"['Martinu, Tereza', 'Pavlisko, Elizabeth N', 'Chen, Dong-Feng', 'Palmer, Scott M.']",,,,
,PMC,The Asia Pacific Strategy for Emerging Diseases – a strategy for regional health security,http://dx.doi.org/10.5365/WPSAR.2011.2.1.001,PMC3729053,,,,,"['Li, Ailan', 'Kasai, Takeshi']",,,,
,PMC,Different host cell proteases activate the SARS-coronavirus spike-protein for cell-cell and virus-cell fusion,http://dx.doi.org/10.1016/j.virol.2011.02.020,PMC3086175,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) poses a considerable threat to human health. Activation of the viral spike (S)-protein by host cell proteases is essential for viral infectivity. However, the cleavage sites in SARS-S and the protease(s) activating SARS-S are incompletely defined. We found that R667 was dispensable for SARS-S-driven virus-cell fusion and for SARS-S-activation by trypsin and cathepsin L in a virus-virus fusion assay. Mutation T760R, which optimizes the minimal furin consensus motif 758-RXXR-762, and furin overexpression augmented SARS-S-activity, but did not result in detectable SARS-S cleavage. Finally, SARS-S-driven cell-cell fusion was independent of cathepsin L, a protease essential for virus-cell fusion. Instead, a so far unknown leupeptin-sensitive host cell protease activated cellular SARS-S for fusion with target cells expressing high levels of ACE2. Thus, different host cell proteases activate SARS-S for virus-cell and cell-cell fusion and SARS-S cleavage at R667 and 758-RXXR-762 can be dispensable for SARS-S activation.",,"['Simmons, Graham', 'Bertram, Stephanie', 'Glowacka, Ilona', 'Steffen, Imke', 'Chaipan, Chawaree', 'Agudelo, Juliet', 'Lu, Kai', 'Rennekamp, Andrew J.', 'Hofmann, Heike', 'Bates, Paul', 'Pöhlmann, Stefan']",,,,
,PMC,Alterations in the proteome of the NHERF2 knockout mouse jejunal brush border membrane vesicles,http://dx.doi.org/10.1152/physiolgenomics.00258.2010,PMC3121161,,,"To identify additional potential functions for the multi-PDZ domain containing protein Na(+)/H(+) exchanger regulatory factor 2 (NHERF2), which is present in the apical domain of intestinal epithelial cells, proteomic studies of mouse jejunal villus epithelial cell brush border membrane vesicles compared wild-type to homozygous NHERF2 knockout FVB mice by a two-dimensional liquid chromatography-tandem mass spectrometry (LC-MS/MS)-iTRAQ approach. Jejunal architecture appeared normal in NHERF2 null in terms of villus length and crypt depth, Paneth cell number, and microvillus structure by electron microscopy. There was also no change in proliferative activity based on BrdU labeling. Four brush border membrane vesicles (BBMV) preparations from wild-type mouse jejunum were compared with four preparations from NHERF2 knockout mice. LC-MS/MS identified 450 proteins in both matched wild-type and NHERF2 null BBMV; 13 proteins were changed in two or more separate BBMV preparations (9 increased and 4 decreased in NHERF2 null mice), while an additional 92 proteins were changed in a single BBMV preparation (68 increased and 24 decreased in NHERF2 null mice). These proteins were categorized as 1) transport proteins (one increased and two decreased in NHERF2 null); 2) signaling molecules (2 increased in NHERF2 null); 3) cytoskeleton/junctional proteins (4 upregulated and 1 downregulated in NHERF2 null); and 4) metabolic proteins/intrinsic BB proteins) (2 upregulated and 1 downregulated in NHERF2 null). Immunoblotting of BBMV was used to validate or extend the findings, demonstrating increase in BBMV of NHERF2 null of MCT1, coronin 3, and ezrin. The proteome of the NHERF2 null mouse small intestinal BB demonstrates up- and downregulation of multiple transport proteins, signaling molecules, cytoskeletal proteins, tight junctional and adherens junction proteins, and proteins involved in metabolism, suggesting involvement of NHERF2 in multiple apical regulatory processes and interactions with luminal contents.",,"['Donowitz, M.', 'Singh, S.', 'Singh, P.', 'Chakraborty, M.', 'Chen, Y.', 'Murtazina, R.', 'Gucek, M.', 'Cole, R. N.', 'Zachos, N. C.', 'Salahuddin, F. F.', 'Kovbasnjuk, O.', 'Broere, N.', 'Smalley-Freed, W. G.', 'Reynolds, A. B.', 'Hubbard, A. L.', 'Seidler, U.', 'Weinman, E.', 'de Jonge, H. R.', 'Hogema, B. M.', 'Li, X.']",,,,
,PMC,Randomized Trial of Omalizumab (Anti-IgE) for Asthma in Inner-City Children,http://dx.doi.org/10.1056/NEJMoa1009705,PMC3093964,,,"BACKGROUND: Research has underscored the effects of exposure and sensitization to allergens on the severity of asthma in inner-city children. It has also revealed the limitations of environmental remediation and guidelines-based therapy in achieving greater disease control. METHODS: We enrolled inner-city children, adolescents, and young adults with persistent asthma in a randomized, double-blind, placebo-controlled, parallel-group trial at multiple centers to assess the effectiveness of omalizumab, as compared with placebo, when added to guidelines-based therapy. The trial was conducted for 60 weeks, and the primary outcome was symptoms of asthma. RESULTS: Among 419 participants who underwent randomization (at which point 73% had moderate or severe disease), omalizumab as compared with placebo significantly reduced the number of days with asthma symptoms, from 1.96 to 1.48 days per 2-week interval, a 24.5% decrease (P<0.001). Similarly, omalizumab significantly reduced the proportion of participants who had one or more exacerbations from 48.8 to 30.3% (P<0.001). Improvements occurred with omalizumab despite reductions in the use of inhaled glucocorticoids and long-acting beta-agonists. CONCLUSIONS: When added to a regimen of guidelines-based therapy for inner-city children, adolescents, and young adults, omalizumab further improved asthma control, nearly eliminated seasonal peaks in exacerbations, and reduced the need for other medications to control asthma. (Funded by the National Institute of Allergy and Infectious Diseases and Novartis; ClinicalTrials.gov number, NCT00377572.)",,"['Busse, William W.', 'Morgan, Wayne J.', 'Gergen, Peter J.', 'Mitchell, Herman E.', 'Gern, James E.', 'Liu, Andrew H.', 'Gruchalla, Rebecca S.', 'Kattan, Meyer', 'Teach, Stephen J.', 'Pongracic, Jacqueline A.', 'Chmiel, James F.', 'Steinbach, Suzanne F.', 'Calatroni, Agustin', 'Togias, Alkis', 'Thompson, Katherine M.', 'Szefler, Stanley J.', 'Sorkness, Christine A.']",,,,
,PMC,Common cold,,PMC3275147,,,"INTRODUCTION: Each year, children suffer up to 5 colds and adults have two to three infections, leading to time off school or work, and considerable discomfort. Most symptoms resolve within 1 week, but coughs often persist for longer. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for common cold? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 21 systematic reviews and RCTs that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: analgesics or anti-inflammatory drugs, antibiotics, antihistamines, decongestants for short-term and for long-term relief, decongestants plus antihistamines, echinacea, steam inhalation, vitamin C, and zinc (intranasal gel or lozenges).",,"Arroll, Bruce",,,,
,PMC,Impact of Imitation Processes on the Effectiveness of Ring Vaccination,http://dx.doi.org/10.1007/s11538-011-9646-4,PMC3409595,,,"Ring vaccination can be a highly effective control strategy for an emerging disease or in the final phase of disease eradication, as witnessed in the eradication of smallpox. However, the impact of behavioural dynamics on the effectiveness of ring vaccination has not been explored in mathematical models. Here, we analyze a series of stochastic models of voluntary ring vaccination. Contacts of an index case base vaccinating decisions on their own individual payoffs to vaccinate or not vaccinate, and they can also imitate the behaviour of other contacts of the index case. We find that including imitation changes the probability of containment through ring vaccination considerably. Imitation can cause a strong majority of contacts to choose vaccination in some cases, or to choose non-vaccination in other cases—even when the equivalent solution under perfectly rational (non-imitative) behaviour yields mixed choices. Moreover, imitation processes can result in very different outcomes in different stochastic realizations sampled from the same parameter distributions, by magnifying moderate tendencies toward one behaviour or the other: in some realizations, imitation causes a strong majority of contacts not to vaccinate, while in others, imitation promotes vaccination and reduces the number of secondary infections. Hence, the effectiveness of ring vaccination can depend significantly and unpredictably on imitation processes. Therefore, our results suggest that risk communication efforts should be initiated early in an outbreak when ring vaccination is to be applied, especially among subpopulations that are heavily influenced by peer opinions.",,"['Wells, Chad R.', 'Tchuenche, Jean M.', 'Meyers, Lauren Ancel', 'Galvani, Alison P.', 'Bauch, Chris T.']",,,,
,PMC,Inhibition of Ebola Virus Entry by a C-peptide Targeted to Endosomes,http://dx.doi.org/10.1074/jbc.M110.207084,PMC3091195,,,"Ebola virus (EboV) and Marburg virus (MarV) (filoviruses) are the causative agents of severe hemorrhagic fever. Infection begins with uptake of particles into cellular endosomes, where the viral envelope glycoprotein (GP) catalyzes fusion between the viral and host cell membranes. This fusion event is thought to involve conformational rearrangements of the transmembrane subunit (GP2) of the envelope spike that ultimately result in formation of a six-helix bundle by the N- and C-terminal heptad repeat (NHR and CHR, respectively) regions of GP2. Infection by other viruses employing similar viral entry mechanisms (such as HIV-1 and severe acute respiratory syndrome coronavirus) can be inhibited with synthetic peptides corresponding to the native CHR sequence (“C-peptides”). However, previously reported EboV C-peptides have shown weak or insignificant antiviral activity. To determine whether the activity of a C-peptide could be improved by increasing its intracellular concentration, we prepared an EboV C-peptide conjugated to the arginine-rich sequence from HIV-1 Tat, which is known to accumulate in endosomes. We found that this peptide specifically inhibited viral entry mediated by filovirus GP proteins and infection by authentic filoviruses. We determined that antiviral activity was dependent on both the Tat sequence and the native EboV CHR sequence. Mechanistic studies suggested that the peptide acts by blocking a membrane fusion intermediate.",,"['Miller, Emily Happy', 'Harrison, Joseph S.', 'Radoshitzky, Sheli R.', 'Higgins, Chelsea D.', 'Chi, Xiaoli', 'Dong, Lian', 'Kuhn, Jens H.', 'Bavari, Sina', 'Lai, Jonathan R.', 'Chandran, Kartik']",,,,
,PMC,Truly Emerging — A New Disease Caused by a Novel Virus,http://dx.doi.org/10.1056/NEJMe1102671,PMC4830420,,,,,"Feldmann, Heinz",,,,
,PMC,Modulation of NF-κB signalling by microbial pathogens,http://dx.doi.org/10.1038/nrmicro2539,PMC3611960,,,"The nuclear factor-κB (NF-κB) family of transcription factors plays a central part in the host response to infection by microbial pathogens, by orchestrating the innate and acquired host immune responses. The NF-κB proteins are activated by diverse signalling pathways that originate from many different cellular receptors and sensors. Many successful pathogens have acquired sophisticated mechanisms to regulate the NF-κB signalling pathways by deploying subversive proteins or hijacking the host signalling molecules. Here, we describe the mechanisms by which viruses and bacteria micromanage the host NF-κB signalling circuitry to favour the continued survival of the pathogen.",,"['Rahman, Masmudur M.', 'McFadden, Grant']",,,,
,PMC,A nationwide web-based automated system for outbreak early detection and rapid response in China,http://dx.doi.org/10.5365/WPSAR.2010.1.1.009,PMC3729055,,,"Timely reporting, effective analyses and rapid distribution of surveillance data can assist in detecting the aberration of disease occurrence and further facilitate a timely response. In China, a new nationwide web-based automated system for outbreak detection and rapid response was developed in 2008. The China Infectious Disease Automated-alert and Response System (CIDARS) was developed by the Chinese Center for Disease Control and Prevention based on the surveillance data from the existing electronic National Notifiable Infectious Diseases Reporting Information System (NIDRIS) started in 2004. NIDRIS greatly improved the timeliness and completeness of data reporting with real-time reporting information via the Internet. CIDARS further facilitates the data analysis, aberration detection, signal dissemination, signal response and information communication needed by public health departments across the country. In CIDARS, three aberration detection methods are used to detect the unusual occurrence of 28 notifiable infectious diseases at the county level and transmit information either in real time or on a daily basis. The Internet, computers and mobile phones are used to accomplish rapid signal generation and dissemination, timely reporting and reviewing of the signal response results. CIDARS has been used nationwide since 2008; all Centers for Disease Control and Prevention (CDC) in China at the county, prefecture, provincial and national levels are involved in the system. It assists with early outbreak detection at the local level and prompts reporting of unusual disease occurrences or potential outbreaks to CDCs throughout the country.",,"['Yang, Weizhong', 'Li, Zhongjie', 'Lan, Yajia', 'Wang, Jinfeng', 'Ma, Jiaqi', 'Jin, Lianmei', 'Sun, Qiao', 'Lv, Wei', 'Lai, Shengjie', 'Liao, Yilan', 'Hu, Wenbiao']",,,,
,PMC,Responding to emerging diseases: reducing the risks through understanding the mechanisms of emergence,http://dx.doi.org/10.2471/WPSAR.2011.2.1.006,PMC3729054,,,,,"Mackenzie, John S",,,,
,PMC,Mechanism of HSV infection through soluble adapter-mediated virus bridging to the EGF receptor,http://dx.doi.org/10.1016/j.virol.2011.02.014,PMC3085989,,,"Herpes simplex virus entry into cells requires the binding of envelope glycoprotein D (gD) to an entry receptor. Depending on the cell, entry occurs by different mechanisms, including fusion at the cell surface or endocytosis. Here we examined the entry mechanism through a non-HSV receptor mediated by a soluble bi-specific adapter protein composed of recognition elements for gD and the EGF receptor (EGFR). Virus entered into endosomes using either EGF or an EGFR-specific single chain antibody (scFv) for receptor recognition. Infection was less efficient with the EGF adapter which could be attributed to its weaker binding to viral gD. Infection mediated by the scFv adapter was pH sensitive, indicating that gD-EGFR bridging alone was insufficient for capsid release from endosomes. We also show that the scFv adapter enhanced infection of EGFR-expressing tumor tissue in vivo. Our results indicate that adapters may retarget HSV infection without drastically changing the entry mechanism.",,"['Nakano, Kenji', 'Kobayashi, Masatoshi', 'Nakamura, Kei-ichiro', 'Nakanishi, Takeshi', 'Asano, Ryutaro', 'Kumagai, Izumi', 'Tahara, Hideaki', 'Kuwano, Michihiko', 'Cohen, Justus B.', 'Glorioso, Joseph C.']",,,,
,PMC,Activation of protein kinase R is required for induction of stress granules by respiratory syncytial virus but dispensable for viral replication,http://dx.doi.org/10.1016/j.virol.2011.02.009,PMC3072468,,,"We performed experiments to determine the effect of PKR activation on respiratory syncytial virus (RSV) replication. We first determined that RSV infection activates PKR which induces the phosphorylation of eIF2α, resulting in the formation of host stress granules. We used RNA interference to decrease endogenous PKR levels. RSV replication was not altered in cells deficient for PKR expression. However, RSV-mediated stress granule formation was significantly reduced in PKR-knockdown cells. As an alternative method to block PKR activation, we used treatment with the kinase inhibitor 2-aminopurine (2-AP). We observed that 2-AP treatment significantly reduced viral replication. We also treated PKR-knockdown cells with 2-AP and inoculated with RSV. Under these conditions, 2-AP treatment diminished viral replication in the absence of PKR expression. These results suggest that PKR activation has a minimal effect on RSV replication and that the antiviral effect of 2-AP during RSV infection likely occurs via a PKR-independent mechanism.",,"['Lindquist, Michael E.', 'Mainou, Bernardo A.', 'Dermody, Terence S.', 'Crowe, James E.']",,,,
,PMC,The solution structure of coronaviral stem-loop 2 (SL2) reveals a canonical CUYG tetraloop fold,http://dx.doi.org/10.1016/j.febslet.2011.03.002,PMC3086565,,,"The transcription and replication of the severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is regulated by specific viral genome sequences within 5′- and 3′-untranslated regions (5′-UTR and 3′-UTR). Here we report the solution structure of 5′-UTR derived stem-loop 2 (SL2) of SARS-CoV determined by solution NMR spectroscopy. The highly conserved pentaloop of SL2 is stacked on 5-bp stem and adopts a canonical CUYG tetraloop fold with the 3′ nucleotide (U51) flipped out of the stack. The significance of this structure in the context of a previous mutagenesis analysis of SL2 function in replication of the related group 2 coronavirus, mouse hepatitis virus, is discussed.",,"['Lee, Chul Won', 'Li, Lichun', 'Giedroc, David P.']",,,,
,PMC,HIV envelope: challenges and opportunities for development of entry inhibitors,http://dx.doi.org/10.1016/j.tim.2011.02.001,PMC3071980,,,"The HIV envelope proteins gp120 and gp41 play critical roles in HIV entry and thus are of extreme interest for the development of novel therapeutics. Study by diverse methods, including structural biology and mutagenesis, has resulted in a detailed model for envelope-mediated entry, which consists of multiple conformations, each a potential target for therapeutic intervention. In this review we discuss the challenges, strategies and progress to date for developing novel entry inhibitors directed at disrupting HIV gp120 and gp41 function.",,"Caffrey, Michael",,,,
,PMC,CLEVER-1 Mediates the Transmigration of T Regulatory Cells Across Human Hepatic Sinusoidal Endothelium,http://dx.doi.org/10.4049/jimmunol.1002961,PMC6016742,,,"The common lymphatic endothelial and vascular endothelial receptor (CLEVER-1; also known as FEEL-1 and stabilin-1) is a recycling and intracellular trafficking receptor with multifunctional properties. Here we demonstrate for the first time increased endothelial expression of CLEVER-1/stabilin-1 at sites of leucocyte recruitment to the inflamed human liver including sinusoids, septal vessels and lymphoid follicles in inflammatory liver disease and tumour-associated vessels in hepatocellular carcinoma. We used primary cultures of human sinusoidal endothelial cells (HSEC) to demonstrate that CLEVER-1/stabilin-1 expression is enhanced by hepatocyte growth factor but not by classical proinflammatory cytokines. We then showed that CLEVER-1/stabilin-1 supports T cell transendothelial migration across HSEC under conditions of flow with strong preferential activity for CD4 FoxP3+ regulatory T cells. CLEVER-1/stabilin-1 inhibition reduced Treg transendothelial migration by 40% and when combined with blockade of ICAM-1 and vascular adhesion protein-1 (VAP-1) reduced it by more than 80%. Confocal microscopy demonstrated that 60% of transmigrating Tregs underwent transcellular migration through HSEC via ICAM-1 and VAP-1 rich transcellular pores in close association with CLEVER-1/stabilin-1. Thus CLEVER-1/stabilin-1 and VAP-1 may provide an organ-specific signal for Treg recruitment to the inflamed liver and to hepatocellular carcinoma.",,"['Shetty, Shishir', 'Weston, Christopher J', 'Oo, Ye H', 'Westerlund, Nina', 'Stamataki, Zania', 'Youster, Janine', 'Hubscher, Stefan G', 'Salmi, Marko', 'Jalkanen, Sirpa', 'Lalor, Patricia F', 'Adams, David H']",,,,
,PMC,Mechanisms for Env Glycoprotein Acquisition by Retroviruses,http://dx.doi.org/10.1089/aid.2010.0350,PMC3048835,,,"A mandatory step in the formation of an infectious retroviral particle is the acquisition of its envelope glycoprotein (Env). This step invariably occurs by Env positioning itself in the host membrane at the location of viral budding and being incorporated along with the host membrane into the viral particle. In some ways, this step of the viral life cycle would appear to be imprecise. There is no specific sequence in Env or in the retroviral structural protein, Gag, that is inherently required for the production of an infectious Env-containing particle. Additionally, Env-defective proviruses can efficiently produce infectious particles with any of a number of foreign retroviral Env glycoproteins or even glycoproteins from unrelated viral families, a process termed pseudotyping. However, mounting evidence suggests that Env incorporation is neither passive nor random. Rather, several redundant mechanisms appear to contribute to the carefully controlled process of Env acquisition, many of which are apparently used by a wide variety of enveloped viruses. This review presents and discusses the evidence for these different mechanisms contributing to incorporation.",,"Johnson, Marc C.",,,,
,PMC,Promoting Health Near and Far,http://dx.doi.org/10.2105/AJPH.2010.300103,PMC3036685,,,,,"Dickens, Bernard M.",,,,
,PMC,EPIDEMIOLOGY and Health Care Reform The National Health Survey of 1935-1936,http://dx.doi.org/10.2105/AJPH.2010.196519,PMC3036678,,,"The National Health Survey undertaken in 1935 and 1936 was the largest morbidity survey until that time. It was also the first national survey to focus on chronic disease and disability. The decision to conduct a survey of this magnitude was part of the larger strategy to reform health care in the United States. The focus on morbidity allowed reformers to argue that the health status of Americans was poor, despite falling mortality rates that suggested the opposite. The focus on chronic disease morbidity proved to be an especially effective way of demonstrating the poor health of the population and the strong links between poverty and illness. The survey, undertaken by a small group of reform-minded epidemiologists led by Edgar Sydenstricker, was made possible by the close interaction during the Depression of agencies and actors in the public health and social welfare sectors, a collaboration which produced new ways of thinking about disease burdens.",,"Weisz, George",,,,
,PMC,Oligomeric procyanidins stimulate innate antiviral immunity in dengue virus infected human PBMCs,http://dx.doi.org/10.1016/j.antiviral.2011.02.011,PMC3076897,,,"Oligomeric procyanidins (OPCs) have been shown to have antiviral and immunostimulatory effects. OPCs isolated from non-ripe apple peel were tested for capacity to reduce dengue virus (DENV) titers. Similar to published accounts, OPCs exhibited direct antiviral activity. The possibility of enhanced innate immune protection was also tested by measuring and characterizing gene and protein expression induced by OPCs during DENV infection. Treatment of DENV-infected human PBMCs with OPCs decreased viral titers and affected the expression of critical innate antiviral immune products. OPCs enhanced expression of MXI and IFNB transcripts in high MOI DENV infected PBMC cultures, and phosphorylation of STAT2 in response to recombinant type I IFN (IFN I). During low MOI infection, addition of OPCs increased expression of STAT1 transcripts, MHC I and TNFα protein production. Thus, OPCs exhibited innate immune stimulation of cells in DENV-infected cultures and uninfected cells treated with IFN I. While OPCs from a number of sources are known to exhibit antiviral effects, their mechanisms are not precisely defined. The capacity of OPCs to increase sensitivity to IFN I could be broadly applicable to many viral infections and two separate antiviral mechanisms suggest that OPCs may represent a novel, robust antiviral therapy.",,"['Kimmel, Emily M.', 'Jerome, Maria', 'Holderness, Jeff', 'Snyder, Deann', 'Kemoli, Sharon', 'Jutila, Mark A.', 'Hedges, Jodi F.']",,,,
,PMC,The time of cholera,,PMC3076148,,,,,"['Fisman, David N', 'Laupland, Kevin']",,,,
,PMC,"Development and Initial Results of a Low Cost, Disposable, Point-of-Care Testing Device for Pathogen Detection",http://dx.doi.org/10.1109/TBME.2010.2089054,PMC3071014,,,"Development of small footprint, disposable, fast, and inexpensive devices for pathogen detection in the field and clinic would benefit human and veterinary medicine by allowing evidence-based responses to future out breaks. We designed and tested an integrated nucleic acid extraction and amplification device employing a loop-mediated isothermal amplification (LAMP) or reverse transcriptase-LAMP assay. Our system provides a screening tool with polymerase-chain-reaction-level sensitivity and specificity for outbreak detection, response, and recovery. Time to result is ~90 min. The device utilizes a swab that collects sample and then transfers it to a disc of cellulose-based nucleic acid binding paper. The disc is positioned within a disposable containment tube with a manual loading port. In order to test for the presence of target pathogens, LAMP reagents are loaded through the tube’s port into contact with the sample containing cellulose disc. The reagents then are isothermally heated to 63°C for ~1 h to achieve sequence-specific target nucleic acid amplification. Due to the presence of a colorimetric dye, amplification induces visible color change in the reagents from purple to blue. As initial demonstrations, we detected methicillin resistant Staphylococcus aureus genomic DNA, as well as recombinant and live foot-and-mouth disease virus.",,"['Bearinger, Jane P.', 'Dugan, Lawrence C.', 'Baker, Brian R.', 'Hall, Sara B.', 'Ebert, Katja', 'Mioulet, Valerie', 'Madi, Mikidache', 'King, Donald P.']",,,,
,PMC,Neuromusculoskeletal disorders following SARS: a case series,,PMC3044805,,,"OBJECTIVE: To detail the presentation of three health care workers diagnosed with sudden acute respiratory syndrome (SARS) who later presented to a CMCC teaching clinic with neuromusculoskeletal sequelae and underwent conservative treatments. This case series aims to inform practitioners of the potential pathogenesis of these neuromuscular complaints and describes their treatment in a chiropractic practice. CLINICAL FEATURES: Three patients presented with a variety of neurological, muscular and joint findings. Conservative treatment was aimed at decreasing hypertonic muscles, increasing joint mobility, and improving ability to perform activities of daily living. INTERVENTION AND OUTCOME: The conservative treatment approach utilized in these cases involved spinal manipulative therapy, soft tissue therapy, modalities, and rehabilitation. Outcome measures included subjective pain ratings, disability indices, and return to work. CONCLUSION: Three patients previously diagnosed with SARS presented with neuromusculoskeletal complaints and subjectively experienced intermittent relief of pain and improvement in disability status after conservative treatments.",,"['Stainsby, Brynne', 'Howitt, Scott', 'Porr, Jason']",,,,
,PMC,Identification of Pseudallescheria and Scedosporium Species by Three Molecular Methods,http://dx.doi.org/10.1128/JCM.01813-10,PMC3067705,,,"The major clinically relevant species in Scedosporium (teleomorph Pseudallescheria) are Pseudallescheria boydii, Scedosporium aurantiacum, Scedosporium apiospermum, and Scedosporium prolificans, while Pseudallescheria minutispora, Petriellopsis desertorum, and Scedosporium dehoogii are exceptional agents of disease. Three molecular methods targeting the partial β-tubulin gene were developed and evaluated to identify six closely related species of the S. apiospermum complex using quantitative real-time PCR (qPCR), PCR-based reverse line blot (PCR-RLB), and loop-mediated isothermal amplification (LAMP). qPCR was not specific enough for the identification of all species but had the highest sensitivity. The PCR-RLB assay was efficient for the identification of five species. LAMP distinguished all six species unambiguously. The analytical sensitivities of qPCR, PCR-RLB, and LAMP combined with MagNAPure, CTAB (cetyltrimethylammonium bromide), and FTA filter (Whatman) extraction were 50, 5 × 10(3), and 5 × 10(2) cells/μl, respectively. When LAMP was combined with a simplified DNA extraction method using an FTA filter, identification to the species level was achieved within 2 h, including DNA extraction. The FTA-LAMP assay is therefore recommended as a cost-effective, simple, and rapid method for the identification of Scedosporium species.",,"['Lu, Qiaoyun', 'Gerrits van den Ende, A. H. G.', 'Bakkers, J. M. J. E.', 'Sun, Jiufeng', 'Lackner, M.', 'Najafzadeh, M. J.', 'Melchers, W. J. G.', 'Li, Ruoyu', 'de Hoog, G. S.']",,,,
,PMC,New insights into the nuclear localization of retroviral Gag proteins,http://dx.doi.org/10.4161/nucl.2.2.15018,PMC3127090,,,"Retroviruses assemble new virus particles that are released by budding from the plasma membranes of infected cells. Gag proteins, encoded by retroviruses, orchestrate the assembly of virus particles in close collaboration with host cell machinery. The earliest steps in retrovirus assembly—those immediately following synthesis of Gag on cytosolic ribosomes—are poorly understood. Rous sarcoma virus (RSV) offers a unique model system for dissecting these early steps because the RSV Gag protein undergoes transient nuclear trafficking prior to plasma membrane transport. Other Gag proteins, including those of human immunodeficiency virus (HIV), murine leukemia virus (MLV), foamy virus and retrotransposons in Schizosaccharomyces pombe and Drosophila, have also been detected in the nucleus, suggesting that nuclear trafficking of Gag proteins is a common property of retroviruses and retrotransposons. In addition to retroviruses, many structural proteins of unrelated viruses, including influenza M1, NEP and NP proteins,38 Borna disease virus N and P proteins28,56 and coronavirus N protein,23,57 undergo nuclear localization and bind viral RNAs to form viral ribonuclear protein (RNP) complexes that are exported from the nucleus for packaging into virus particles. Similarly, nuclear trafficking of the RSV Gag protein is required for efficient encapsidation of the viral genomic RNA (gRNA) into assembling virus particles.19 Recently, we reported that the viral RNA itself appears to be a key factor in controlling the nucleus/cytosol distribution of RSV Gag.22 Our data demonstrate that binding of RSV RNA to the Gag protein promotes Gag-CRM1-RanGTP binding, resulting in export of the retroviral RNP from the nucleus. We propose that association of the viral RNA induces a conformational change in Gag that reveals its nuclear export signal (NES) and prepares that complex for its journey to the plasma membrane for budding. This work challenges existing dogmas regarding the molecular basis of Gag-mediated selection of gRNA for packaging and may lead to novel paradigms for the mechanism of retroviral genome encapsidation.",,"Parent, Leslie J",,,,
,PMC,Diverse roles of host RNA-binding proteins in RNA virus replication,http://dx.doi.org/10.4161/rna.8.2.15391,PMC3230553,,,"Plus-strand (+)RNA viruses co-opt host RNA-binding proteins (RBPs) to perform many functions during viral replication. A few host RBPs have been identified that affect the recruitment of viral (+)RNAs for replication. Other subverted host RBPs help the assembly of the membrane-bound replicase complexes, regulate the activity of the replicase and control minus- or plus-strand RNA synthesis. Host RBPs also affect the stability of viral RNAs, which have to escape cellular RNA degradation pathways. While many host RBPs seem to have specialized functions, others participate in multiple events during infection. Several conserved RBPs, such as eEF1A, hnRNP proteins and the Lsm 1–7 complex, are co-opted by evolutionarily diverse (+)RNA viruses, underscoring some common themes in virus-host interactions. On the other hand, viruses also hijack unique RBPs, suggesting that (+)RNA viruses could utilize different RBPs to perform similar functions. Moreover, different (+) RNA viruses have adapted distinctive strategies for co-opting unique RBPs. Altogether, a deeper understanding of the functions of the host RBPs subverted for viral replication will help development of novel antiviral strategies and give new insights into host RNA biology.",,"['Li, Zhenghe', 'Nagy, Peter D']",,,,
,PMC,RNA-RNA and RNA-protein interactions in coronavirus replication and transcription,http://dx.doi.org/10.4161/rna.8.2.14991,PMC3230552,,,"Coronavirus (CoV) RNA synthesis includes the replication of the viral genome, and the transcription of sgRNAs by a discontinuous mechanism. Both processes are regulated by RNA sequences such as the 5′ and 3′ untranslated regions (UTRs), and the transcription regulating sequences (TRSs) of the leader (TRS-L) and those preceding each gene (TRS-Bs). These distant RNA regulatory sequences interact with each other directly and probably through protein-RNA and protein-protein interactions involving viral and cellular proteins.1 By analogy to other plus-stranded RNA viruses, such as polioviruses, in which translation and replication switch involves a cellular factor (PCBP) and a viral protein (3CD),2 it is conceivable that in CoVs the switch between replication and transcription is also associated with the binding of proteins that are specifically recruited by the replication or transcription complexes. Complexes between RNA motifs such as TRS-L and the TRS-Bs located along the CoV genome are probably formed previously to the transcription start, and most likely promote template-switch of the nascent minus RNA to the TRS-L region.3 Many cellular proteins interacting with regulatory CoV RNA sequences4 are members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family of RNA-binding proteins, involved in mRNA processing and transport, which shuttle between the nucleus and the cytoplasm. In the context of CoV RNA synthesis, these cellular ribonucleoproteins might also participate in RNA-protein complexes to bring into physical proximity TRS-L and distant TRS-B, as proposed for CoV discontinuous transcription.5–7 In this review, we summarize RNA-RNA and RNA-protein interactions that represent modest examples of complex quaternary RNA-protein structures required for the fine-tuning of virus replication. Design of chemically defined replication and transcription systems will help to clarify the nature and activity of these structures.",,"['Sola, Isabel', 'Mateos-Gomez, Pedro A', 'Almazan, Fernando', 'Zuñiga, Sonia', 'Enjuanes, Luis']",,,,
,PMC,Coronaviruses: An RNA proofreading machine regulates replication fidelity and diversity,http://dx.doi.org/10.4161/rna.8.2.15013,PMC3127101,,,"In order to survive and propagate, RNA viruses must achieve a balance between the capacity for adaptation to new environmental conditions or host cells with the need to maintain an intact and replication competent genome. Several virus families in the order Nidovirales, such as the coronaviruses (CoVs) must achieve these objectives with the largest and most complex replicating RNA genomes known, up to 32 kb of positive-sense RNA. The CoVs encode sixteen nonstructural proteins (nsp 1–16) with known or predicted RNA synthesis and modification activities, and it has been proposed that they are also responsible for the evolution of large genomes. The CoVs, including murine hepatitis virus (MHV) and SARS-CoV, encode a 3′-to-5′ exoribonuclease activity (ExoN) in nsp14. Genetic inactivation of ExoN activity in engineered SARS-CoV and MHV genomes by alanine substitution at conserved DE-D-D active site residues results in viable mutants that demonstrate 15- to 20-fold increases in mutation rates, up to 18 times greater than those tolerated for fidelity mutants of other RNA viruses. Thus nsp14-ExoN is essential for replication fidelity, and likely serves either as a direct mediator or regulator of a more complex RNA proofreading machine, a process previously unprecedented in RNA virus biology. Elucidation of the mechanisms of nsp14-mediated proofreading will have major implications for our understanding of the evolution of RNA viruses, and also will provide a robust model to investigate the balance between fidelity, diversity and pathogenesis. The discovery of a protein distinct from a viral RdRp that regulates replication fidelity also raises the possibility that RNA genome replication fidelity may be adaptable to differing replication environments and selective pressures, rather than being a fixed determinant.",,"['Denison, Mark R', 'Graham, Rachel L', 'Donaldson, Eric F', 'Eckerle, Lance D', 'Baric, Ralph S']",,,,
,PMC,Should this event be notified to the World Health Organization? Reliability of the International Health Regulations notification assessment process,http://dx.doi.org/10.2471/BLT.10.083154,PMC3066523,,,"OBJECTIVE: To investigate the reliability of the public health event notification assessment process under the International Health Regulations (2005) (IHR). METHODS: In 2009, 193 National IHR Focal Points (NFPs) were invited to use the decision instrument in Annex 2 of the IHR to determine whether 10 fictitious public health events should be notified to WHO. Each event’s notifiability was assessed independently by an expert panel. The degree of consensus among NFPs and of concordance between NFPs and the expert panel was considered high when more than 70% agreed on a response. FINDINGS: Overall, 74% of NFPs responded. The median degree of consensus among NFPs on notification decisions was 78%. It was high for the six events considered notifiable by the majority (median: 80%; range: 76–91) but low for the remaining four (median: 55%; range: 54–60). The degree of concordance between NFPs and the expert panel was high for the five events deemed notifiable by the panel (median: 82%; range: 76–91) but low (median: 51%; range: 42–60) for those not considered notifiable. The NFPs identified notifiable events with greater sensitivity than specificity (P < 0.001). CONCLUSION: When used by NFPs, the notification assessment process in Annex 2 of the IHR was sensitive in identifying public health events that were considered notifiable by an expert panel, but only moderately specific. The reliability of the assessments could be increased by expanding guidance on the use of the decision instrument and by including more specific criteria for assessing events and clearer definitions of terms.",,"['Haustein, Thomas', 'Hollmeyer, Helge', 'Hardiman, Max', 'Harbarth, Stephan', 'Pittet, Didier']",,,,
,PMC,Attrition of Plasmodium-specific memory CD8 T cells results in decreased protection that is rescued by booster immunization,http://dx.doi.org/10.4049/jimmunol.1003949,PMC3074438,,,"Sterile protection against infection with Plasmodium sporozoites requires high numbers of memory CD8 T-cells. However, infections with unrelated pathogens, as may occur in malaria endemic areas, dramatically decrease pre-existing memory CD8 T-cells. It remains unknown whether unrelated infections will compromise numbers of Plasmodium-specific memory CD8 T-cells and thus limit the duration of anti-malarial immunity generated by subunit vaccination. We show that P. berghei circumsporozoite-specific memory CD8 T-cells underwent significant attrition in numbers in mice subjected to unrelated infections. Attrition was associated with preferential loss of effector memory CD8 T-cells and reduced immunity to P. berghei sporozoite challenge. However, and of relevance to deployment of Plasmodium vaccines in malaria endemic areas, attrition of memory CD8 T-cells was reversed by booster immunization, which restored protection. These data suggest that regular booster immunizations may be required to sustain protective vaccine-induced Plasmodium-specific memory CD8 T-cells in the face of attrition caused by unrelated infections.",,"['Schmidt, Nathan W.', 'Harty, John T.']",,,,
,PMC,"Timely detection of localized excess influenza activity in northern California across patient care, prescription, and laboratory data",http://dx.doi.org/10.1002/sim.3883,PMC3058686,,,"Timely detection of clusters of localized influenza activity in excess of background seasonal levels could improve situational awareness for public health officials and health systems. However, no single data type may capture influenza activity with optimal sensitivity, specificity, and timeliness, and it is unknown which data types could be most useful for surveillance. We compared the performance of ten types of electronic clinical data for timely detection of influenza clusters throughout the 2007/08 influenza season in northern California. Kaiser Permanente Northern California generated zip code-specific daily episode counts for: influenza-like illness (ILI) diagnoses in ambulatory care (AC) and emergency departments (ED), both with and without regard to fever; hospital admissions and discharges for pneumonia and influenza; antiviral drugs dispensed (Rx); influenza laboratory tests ordered (Tests); and tests positive for influenza type A (FluA) and type B (FluB). Four credible events of localized excess illness were identified. Prospective surveillance was mimicked within each data stream using a space-time permutation scan statistic, analyzing only data available as of each day, to evaluate the ability and timeliness to detect the credible events. AC without fever and Tests signaled during all four events and, along with Rx, had the most timely signals. FluA had less timely signals. ED, hospitalizations, and FluB did not signal reliably. When fever was included in the ILI definition, signals were either delayed or missed. Although limited to one health plan, location, and year, these results can inform the choice of data streams for public health surveillance of influenza.",,"['Greene, Sharon K.', 'Kulldorff, Martin', 'Huang, Jie', 'Brand, Richard J.', 'Kleinman, Kenneth P.', 'Hsu, John', 'Platt, Richard']",,,,
,PMC,Crystallization and diffraction analysis of the SARS coronavirus nsp10–nsp16 complex,http://dx.doi.org/10.1107/S1744309111002867,PMC3053173,,,"To date, the SARS coronavirus is the only known highly pathogenic human coronavirus. In 2003, it was responsible for a large outbreak associated with a 10% fatality rate. This positive RNA virus encodes a large replicase polyprotein made up of 16 gene products (nsp1–16), amongst which two methyltransferases, nsp14 and nsp16, are involved in viral mRNA cap formation. The crystal structure of nsp16 is unknown. Nsp16 is an RNA-cap AdoMet-dependent (nucleoside-2′-O-)-methyltransferase that is only active in the presence of nsp10. In this paper, the expression, purification and crystallization of nsp10 in complex with nsp16 are reported. The crystals diffracted to a resolution of 1.9 Å resolution and crystal structure determination is in progress.",,"['Debarnot, Claire', 'Imbert, Isabelle', 'Ferron, François', 'Gluais, Laure', 'Varlet, Isabelle', 'Papageorgiou, Nicolas', 'Bouvet, Mickaël', 'Lescar, Julien', 'Decroly, Etienne', 'Canard, Bruno']",,,,
,PMC,Viral Infection in Acute Exacerbation of Idiopathic Pulmonary Fibrosis,http://dx.doi.org/10.1164/rccm.201010-1752OC,PMC3136996,,,"Rationale: Idiopathic pulmonary fibrosis is a progressive, uniformly fatal interstitial lung disease. An acute exacerbation of idiopathic pulmonary fibrosis is an episode of acute respiratory worsening without an identifiable etiology. Occult viral infection has been proposed as a possible cause of acute exacerbation. Objectives: To use unbiased genomics-based discovery methods to define the role of viruses in acute exacerbation of idiopathic pulmonary fibrosis. Methods: Bronchoalveolar lavage and serum from patients with acute exacerbation of idiopathic pulmonary fibrosis, stable disease, and acute lung injury were tested for viral nucleic acid using multiplex polymerase chain reaction, pan-viral microarray, and high-throughput cDNA sequencing. Measurements and Main Results: Four of forty-three patients with acute exacerbation of idiopathic pulmonary fibrosis had evidence of common respiratory viral infection (parainfluenza [n = 1], rhinovirus [n = 2], coronavirus [n = 1]); no viruses were detected in the bronchoalveolar lavage from stable patients. Pan-viral microarrays revealed additional evidence of viral infection (herpes simplex virus [n = 1], Epstein-Barr virus [n = 2], and torque teno virus [TTV] [n = 12]) in patients with acute exacerbation. TTV infection was significantly more common in patients with acute exacerbation than stable controls (P = 0.0003), but present in a similar percentage of acute lung injury controls. Deep sequencing of a subset of acute exacerbation cases confirmed the presence of TTV but did not identify additional viruses. Conclusions: Viral infection was not detected in most cases of acute exacerbation of idiopathic pulmonary fibrosis. TTV was present in a significant minority of cases, and cases of acute lung injury; the clinical significance of this finding remains to be determined.",,"['Wootton, Sharon Chao', 'Kim, Dong Soon', 'Kondoh, Yasuhiro', 'Chen, Eunice', 'Lee, Joyce S.', 'Song, Jin Woo', 'Huh, Jin Won', 'Taniguchi, Hiroyuki', 'Chiu, Charles', 'Boushey, Homer', 'Lancaster, Lisa H.', 'Wolters, Paul J.', 'DeRisi, Joseph', 'Ganem, Don', 'Collard, Harold R.']",,,,
,PMC,Emerging paramyxoviruses: molecular mechanisms and antiviral strategies,http://dx.doi.org/10.1017/S1462399410001754,PMC3253018,,,"In recent years, several paramyxoviruses have emerged to infect humans, including previously unidentified zoonoses. Hendra and Nipah virus (henipavirus (HNV)) zoonoses were first identified in 1994 or 1998, causing deaths in animals and humans in Australia or Malaysia, respectively. Other paramyxoviruses, such as menangle virus, tioman virus, human metapneumovirus, and avian paramyxovirus-1, with less morbidity in humans, have also been recently identified. Although the Paramyxoviridae family of viruses has been previously recognized as biomedically and veterinarily important, the recent emergence of these paramyxoviruses has increased our attention to this family. Antiviral drugs can be designed to target specific important determinants of the viral/cell life cycle. Therefore, identifying and understanding the mechanistic underpinnings of viral entry, replication, assembly, and budding will be critical in the development of antiviral therapeutic agents. This review focuses on the molecular mechanisms discovered and the antiviral strategies pursued in recent years for emerging paramyxoviruses, with a concentration on viral entry and exit mechanisms.",,"['Aguilar, Hector C.', 'Lee, Benhur']",,,,
,PMC,Viral RNAi suppressor reversibly binds siRNA to outcompete Dicer and RISC via multiple-turnover,http://dx.doi.org/10.1016/j.jmb.2011.02.038,PMC3073027,,,"RNA interference (RNAi) is a conserved gene regulatory mechanism employed by most eukaryotes as a key component of their innate immune response against viruses and retrotransposons. During viral infection, the RNase III-type endonuclease Dicer cleaves viral double-stranded RNA into small interfering RNAs (siRNAs), 21–24 nucleotides in length, and helps load them into the RNA-induced silencing complex (RISC) to guide cleavage of complementary viral RNA. As a countermeasure, many viruses have evolved viral RNA silencing suppressor (RSS) proteins that tightly, and presumably quantitatively, bind siRNAs to thwart RNAi-mediated degradation. Viral RSS proteins also act across kingdoms as potential immunosuppressors in gene therapeutic applications. Here we report fluorescence quenching and electrophoretic mobility shift assays that probe siRNA binding by the dimeric RSS p19 from Carnation Italian Ringspot Virus (CIRV), as well as by human Dicer and RISC assembly complexes. We find that the siRNA:p19 interaction is readily reversible, characterized by rapid binding ((1.69 ± 0.07)×10(8) M(−1)s(−1)) and marked dissociation (k(off) = 0.062 ± 0.002 s(−1)). We also observe that p19 efficiently competes with recombinant Dicer and inhibits formation of RISC-related assembly complexes found in human cell extract. Computational modeling based on these results provides evidence for the transient formation of a ternary complex between siRNA, human Dicer, and p19. An expanded model of RNA silencing indicates that multiple-turnover by reversible binding of siRNAs potentiates the efficiency of the suppressor protein. Our predictive model is expected to be applicable to the dosing of p19 as a silencing suppressor in viral gene therapy.",,"['Rawlings, Renata A.', 'Krishnan, Vishalakshi', 'Walter, Nils G.']",,,,
,PMC,Functional Analysis of Two Cavities in Flavivirus NS5 Polymerase,http://dx.doi.org/10.1074/jbc.M110.214189,PMC3077636,,,"Flavivirus NS5 protein encodes methyltransferase and RNA-dependent RNA polymerase (RdRp) activities. Structural analysis of flavivirus RdRp domains uncovered two conserved cavities (A and B). Both cavities are located in the thumb subdomains and represent potential targets for development of allosteric inhibitors. In this study, we used dengue virus as a model to analyze the function of the two RdRp cavities. Amino acids from both cavities were subjected to mutagenesis analysis in the context of genome-length RNA and recombinant NS5 protein; residues critical for viral replication were subjected to revertant analysis. For cavity A, we found that only one (Lys-756) of the seven selected amino acids is critical for viral replication. Alanine substitution of Lys-756 did not affect the RdRp activity, suggesting that this residue functions through a nonenzymatic mechanism. For cavity B, all four selected amino acids (Leu-328, Lys-330, Trp-859, and Ile-863) are critical for viral replication. Biochemical and revertant analyses showed that three of the four mutated residues (Leu-328, Trp-859, and Ile-863) function at the step of initiation of RNA synthesis, whereas the fourth residue (Lys-330) functions by interacting with the viral NS3 helicase domain. Collectively, our results have provided direct evidence for the hypothesis that cavity B, but not cavity A, from dengue virus NS5 polymerase could be a target for rational drug design.",,"['Zou, Gang', 'Chen, Yen-Liang', 'Dong, Hongping', 'Lim, Chin Chin', 'Yap, Li Jian', 'Yau, Yin Hoe', 'Shochat, Susana Geifman', 'Lescar, Julien', 'Shi, Pei-Yong']",,,,
,PMC,Bax and Calpain Mediate Excitotoxic Oligodendrocyte Death Induced by Activation of Both AMPA and Kainate Receptors,http://dx.doi.org/10.1523/JNEUROSCI.5578-10.2011,PMC6623763,,,"Sustained activation of AMPA and kainate receptors in rat oligodendrocytes induces cytosolic calcium overload, mitochondrial depolarization, and an increase of reactive oxygen species, resulting in cell death. Here, we provide evidence that Bax, a proapoptotic member of the Bcl-2 protein family, is involved in excitotoxic apoptotic death of oligodendrocytes and that calpain mediates Bax activation. Cultured Bax(−/−) oligodendrocytes, obtained from the optic nerve of Bax knock-out mice, were resistant to AMPA and kainate receptor-mediated insults. In turn, both mitochondrial calcium uptake and mitochondrial alterations after excitotoxic insults were diminished in Bax-null oligodendrocytes. Moreover, pretreatment with furosemide, a blocker of Bax translocation to mitochondria, significantly protected rat and mouse oligodendrocytes from AMPA- and kainate-induced damage; in contrast, bongkrekic acid, a blocker of the mitochondrial permeability transition pore, had no effect. Finally, we analyzed the participation of calpain, which cleaves Bax and is activated by AMPA and kainate, in oligodendrocyte death. Pretreatment with 3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid (PD150606), a broad cell-permeable calpain inhibitor, and two additional calpain inhibitors diminished Bax activation, inhibited its translocation to mitochondria, and attenuated all apoptotic events resulting from excitotoxic insults to rat oligodendrocytes. Together, these results indicate that Bax and calpain are essential intermediaries of the mitochondria-dependent death pathway, triggered by AMPA and kainate receptor activation in oligodendrocytes.",,"['Sánchez-Gómez, María Victoria', 'Alberdi, Elena', 'Pérez-Navarro, Esther', 'Alberch, Jordi', 'Matute, Carlos']",,,,
,PMC,Estimating reproduction numbers for adults and children from case data,http://dx.doi.org/10.1098/rsif.2010.0679,PMC3140718,,,"We present a method for estimating reproduction numbers for adults and children from daily onset data, using pandemic influenza A(H1N1) data as a case study. We investigate the impact of different underlying transmission assumptions on our estimates, and identify that asymmetric reproduction matrices are often appropriate. Under-reporting of cases can bias estimates of the reproduction numbers if reporting rates are not equal across the two age groups. However, we demonstrate that the estimate of the higher reproduction number is robust to disproportionate data-thinning. Applying the method to 2009 pandemic influenza H1N1 data from Japan, we demonstrate that the reproduction number for children was considerably higher than that of adults, and that our estimates are insensitive to our choice of reproduction matrix.",,"['Glass, K.', 'Mercer, G. N.', 'Nishiura, H.', 'McBryde, E. S.', 'Becker, N. G.']",,,,
,PMC,Deletion of the A35 Gene from Modified Vaccinia Virus Ankara Increases Immunogenicity and Isotype Switching,http://dx.doi.org/10.1016/j.vaccine.2011.02.023,PMC3078999,,,"We show here that the immunogenicity of the Modified Vaccinia Ankara MVA vaccine strain can be improved by deletion of the A35 gene, without diminishing the ability of the virus to replicate. Deletion of the A35 gene resulted in increased virus-specific immunoglobulin production, class switching to IgG isotypes, and virus-specific IFNγ secreting splenocytes. The MVA35 deletion virus provided excellent protective efficacy against virulent virus challenge. These results suggest that A35 deletion mutant strains will have superior vaccine performance for poxvirus vaccines as well as platform vaccines for other infectious diseases and cancer.",,"['Rehm, Kristina E.', 'Roper, Rachel L.']",,,,
,PMC,Infection of cultured bovine cells with bovine herpesvirus 1 (BHV-1) or Sendai virus induces different beta interferon subtypes,http://dx.doi.org/10.1016/j.virusres.2011.02.004,PMC3078687,,,"In contrast to mice or humans, cattle contain three beta interferon (IFN-β) genes with distinct transcriptional promoters suggesting IFN-β gene expression is not stimulated the same by different viruses. To test this hypothesis, we compared expression of the three IFN-β subtypes after infection with a RNA virus, Sendai, versus a large DNA virus, bovine herpesvirus 1 (BHV-1). Infection of low passage bovine kidney (BK) or established bovine kidney cells (CRIB) with Sendai virus has consistently led to high levels of IFN-β1 RNA. Conversely, infection of CRIB cells, but not BK cells, with BHV-1 increased IFN-β3 RNA levels and to a lesser extent the other two IFN-β subtypes. Inhibition of de novo protein synthesis with cycloheximide resulted in higher levels of IFN-β1 and IFN-β2 RNA levels after BHV-1 infection. Further studies demonstrated that BHV-1 immediate early and/or early genes were primarily responsible for inhibiting the IFN response in BK cells. The three bovine IFN-β promoters were cloned upstream of a reporter gene construct, and their properties analyzed in transient transfection assays. Only the IFN-β3 promoter was trans-activated by IRF3 (interferon responsive factor 3). IRF7 and double stranded RNA (polyIC) stimulated IFN-β1 and IFN-β3 promoter activity, but not IFN-β2. Relative to the human IFN-β promoter, the IFN-β3 promoter contained fewer nucleotide differences in the positive regulatory domain III (PRD III), PRD IV, and PRD I compared to the IFN-β1 and IFN-β2 promoter. Collectively, these studies provide evidence that virus infection differentially stimulates expression of the three bovine IFN-β genes.",,"['da Silva, Leticia Frizzo', 'Jones, Clinton']",,,,
,PMC,Viral Metagenome Analysis to Guide Human Pathogen Monitoring in Environmental Samples,http://dx.doi.org/10.1111/j.1472-765X.2011.03014.x,PMC3055918,,,"AIMS: The aim of this study was to develop and demonstrate an approach for describing the diversity of human pathogenic viruses in an environmentally isolated viral metagenome. METHODS AND RESULTS: In silico bioinformatic experiments were used to select an optimum annotation strategy for discovering human viruses in virome datasets, and applied to annotate a class B biosolids virome. Results from the in silico study indicated that less than 1% errors in virus identification could be achieved when nucleotide-based search programs (BLASTn or tBLASTx), viral genome only databases, and sequence reads greater than 200 nt were considered. Within the 51,925 annotated sequences, 94 DNA and 19 RNA sequences were identified as human viruses. Virus diversity included environmentally transmitted agents such as parechovirus, coronavirus, adenovirus, and aichi virus, as well as viruses associated with chronic human infections such as human herpes and hepatitis C viruses. CONCLUSIONS: This study provided a bioinformatic approach for identifying pathogens in a virome dataset, and demonstrated the human virus diversity in a relevant environmental sample. SIGNIFICANCE AND IMPACT OF STUDY: As the costs of next generation sequencing decrease, the pathogen diversity described by virus metagenomes will provide an unbiased guide for subsequent cell-culture and quantitative pathogen analyses, and ensures that highly enriched and relevant pathogens are not neglected in exposure and risk assessments.",,"['Bibby, Kyle', 'Viau, Emily', 'Peccia, Jordan']",,,,
,PMC,Molecular Virology of Hepatitis E Virus,http://dx.doi.org/10.1016/j.virusres.2011.02.011,PMC3130092,,,"This review details the molecular virology of the hepatitis E virus (HEV). While replicons and in vitro infection systems have recently become available, a lot of information on HEV has been generated through comparisons with better-studied positive-strand RNA viruses and through subgenomic expression of viral open reading frames. These models are now being verified with replicon and infection systems. We provide here the current knowledge on the HEV genome and its constituent proteins - ORF1, ORF2 and ORF3. Based on the available information, we also modify the existing model of the HEV life cycle.",,"['Ahmad, Imran', 'Holla, R. Prasida', 'Jameel, Shahid']",,,,
,PMC,"Inhibition of severe acute respiratory syndrome coronavirus replication in a lethal SARS-CoV BALB/c mouse model by stinging nettle lectin, Urtica dioica agglutinin",http://dx.doi.org/10.1016/j.antiviral.2011.02.003,PMC3085190,,,"Urtica dioica agglutinin (UDA) is a small plant monomeric lectin, 8.7 kDa in size, with an N-acetylglucosamine specificity that inhibits viruses from Nidovirales in vitro. In the current study, we first examined the efficacy of UDA on the replication of different SARS-CoV strains in Vero 76 cells. UDA inhibited virus replication in a dose-dependent manner and reduced virus yields of the Urbani strain by 90% at 1.1 ± 0.4 µg/ml in Vero 76 cells. Then, UDA was tested for efficacy in a lethal SARS-CoV-infected BALB/c mouse model. BALB/c mice were infected with two LD(50) (575 PFU) of virus for 4 hours before the mice were treated intraperitoneally with UDA at 20, 10, 5 or 0 mg/kg/day for 4 days. Treatment with UDA at 5 mg/kg significantly protected the mice against a lethal infection with mouse-adapted SARS-CoV (p<0.001), but did not significantly reduce virus lung titers. All virus-infected mice receiving UDA treatments were also significantly protected against weight loss (p<0.001). UDA also effectively reduced lung pathology scores. At day 6 after virus exposure, all groups of mice receiving UDA had much lower lung weights than did the placebo-treated mice. Thus, our data suggest that UDA treatment of SARS infection in mice leads to a substantial therapeutic effect that protects mice against death and weight loss. Furthermore, the mode of action of UDA in vitro was further investigated using live SARS-CoV Urbani strain virus and retroviral particles pseudotyped with SARS-CoV spike (S). UDA specifically inhibited the replication of live SARS-CoV or SARS-CoV pseudotyped virus when added just before, but not after, adsorption. These data suggested that UDA likely inhibits SARS-CoV infection by targeting early stages of the replication cycle, namely, adsorption or penetration. In addition, we demonstrated that UDA neutralizes the virus infectivity, presumably by binding to the SARS-CoV spike (S) glycoprotein. Finally, the target molecule for inhibition of virus replication was partially characterized. When UDA was exposed to N-acetylglucosamine and then UDA was added to cells just prior to adsorption, UDA did not inhibit the virus infection. These data support the conclusion that UDA might bind to N-acetylglucosamine-like residues present on the glycosylated envelope glycoproteins, thereby preventing virus attachment to cells.",,"['Kumaki, Yohichi', 'Wandersee, Miles K.', 'Smith, Aaron J.', 'Zhou, Yanchen', 'Simmons, Graham', 'Nelson, Nathan M.', 'Bailey, Kevin W.', 'Vest, Zachary G.', 'Li, Joseph K.-K.', 'Chan, Paul Kay-Sheung', 'Smee, Donald F.', 'Barnard, Dale L.']",,,,
,PMC,Lipid Peroxidation Correlates with HIVmRNA in Serodiscordant Heterosexual HIVpartners of Nigerian Origin,http://dx.doi.org/10.1007/s12291-011-0120-8,PMC3162947,,,"We recruited 59 individuals of known HIV serostatus after informed consent however, 44 were serodiscordant heterosexual partners [serodiscordant seronegative (SSN group) and serodiscordant seropositive (SSP group)] while 15 were seronegative healthy individuals (SNH). In the case–control study we choose to determine Malondialdehyde (MDA) concentration as a marker of lipid peroxidation index (oxidative stress) spectrophotometrically and quantify HIV mRNA by Real Time-nucleic acid sequence based amplification assay (RT-NASBA). Here our result show for the first time a high concentration of lipid peroxidation product (MDA, 116.6%) with a significant (P < 0.05) increase in HIV serodiscordant seropositive subjects over their seronegative partners. However, Spearman rank correlation statistics of SSP group showed a positive correlation value (P < 0.01, r = 0.89) between MDA and mRNA and a negative correlation between MDA and T-cell ratio (P < 0.01, r = 0.96).The study may strongly indicate a possible lipid peroxidation product threshold for predicting HIV infection and progression in serodiscordant heterosexual partners.",,"['Ibeh, Bartholomew O.', 'Obidoa, Onyechi', 'Nwuke, Chinedu']",,,,
,PMC,Down-regulation of granulocyte-macrophage colony-stimulating factor by 3C-like proteinase in transfected A549 human lung carcinoma cells,http://dx.doi.org/10.1186/1471-2172-12-16,PMC3048559,21324206,CC BY,"BACKGROUND: Severe Acute Respiratory Syndrome (SARS) is a severe respiratory illness caused by a novel virus, the SARS coronavirus (SARS-CoV). 3C-like protease (3CL(pro)) of SARS-CoV plays a role in processing viral polypeptide precursors and is responsible of viral maturation. However, the function of 3CL(pro )in host cells remains unknown. This study investigated how the 3CL(pro )affected the secretion of cytokines in the gene-transfected cells. RESULTS: From immunofluorescence microscopy, the localization of c-myc tagged 3CL(pro )was detected both in the cytoplasm and nucleus of transfected A549 cells. Expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly decreased in 3CL(pro)-transfected cells by both RT-PCR and ELISA, but without changes in other cytokines, i.e., IL-1β, IL-6, IL-8, IL12p40, TNF-α, and TGF-β. Furthermore, the protein levels of NF-kB decreased in 3CL(pro)-transfected A549 cells when compared to EGFP transfected cells. CONCLUSIONS: Our results suggest that the 3CL(pro )may suppress expression of GM-CSF in transfected A549 cells through down-regulation of NF-kB production.",2011 Feb 17,"['Liao, Hsien-Hua', 'Wang, Yao-Chen', 'Chen, Miles Chih-Ming', 'Tsai, Hsien-Yu', 'Lin, Johnson', 'Chen, Shui-Tein', 'Tsay, Gregory Jiazer', 'Cheng, Sun-Long']",BMC Immunol,,,
,PMC,Virus interactions with human signal transduction pathways,http://dx.doi.org/10.1504/IJCBDD.2011.038658,PMC3407688,,,"Viruses depend on their hosts at every stage of their life cycles and must therefore communicate with them via Protein-Protein Interactions (PPIs). To investigate the mechanisms of communication by different viruses, we overlay reported pairwise human-virus PPIs on human signalling pathways. Of 671 pathways obtained from NCI and Reactome databases, 355 are potentially targeted by at least one virus. The majority of pathways are linked to more than one virus. We find evidence supporting the hypothesis that viruses often interact with different proteins depending on the targeted pathway. Pathway analysis indicates overrepresentation of some pathways targeted by viruses. The merged network of the most statistically significant pathways shows several centrally located proteins, which are also hub proteins. Generally, hub proteins are targeted more frequently by viruses. Numerous proteins in virus-targeted pathways are known drug targets, suggesting that these might be exploited as potential new approaches to treatments against multiple viruses.",,"['Zhao, Zhongming', 'Xia, Junfeng', 'Tastan, Oznur', 'Singh, Irtisha', 'Kshirsagar, Meghana', 'Carbonell, Jaime', 'Klein-Seetharaman, Judith']",,,,
,PMC,Validation of Assays to Monitor Immune Responses in the Syrian Golden Hamster (Mesocricetus auratus),http://dx.doi.org/10.1016/j.jim.2011.02.004,PMC3085612,,,"The Syrian Golden hamster (Mesocricetus auratus) is a valuable but under-utilized animal model for studies of human viral pathogens such as bunyaviruses, arenaviruses, flaviviruses, henipaviruses, and SARS-coronavirus. A lack of suitable reagents and specific assays for monitoring host responses has limited the use of this animal model to clinical observations, pathology and humoral immune responses. The objective of this study was to establish and validate assays to monitor host immune responses in the hamster including important pro-inflammatory, anti-inflammatory and innate immune responses, as well as markers of apoptosis, cell proliferation, cell junction integrity and coagulation. Commercially available mouse and rat ELISA and luminex panels were screened for potential cross-reactivity, but were found to be of limited value for studying host responses in hamsters. Subsequently, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays for the detection of 51 immune-related and four internal reference genes were developed. To validate the immune-related assays, hamsters were infected with vesicular stomatitis virus (VSV), Indiana species, or treated with lipopolysaccharide (LPS) and host immune responses were monitored in selected organs. Ribosomal protein L18 was identified as the most stable internal reference gene. In conclusion, these new assays will greatly improve the use of the hamster as an important small animal model in infectious disease research.",,"['Zivcec, Marko', 'Safronetz, David', 'Haddock, Elaine', 'Feldmann, Heinz', 'Ebihara, Hideki']",,,,
,PMC,Arenavirus Reverse Genetics: New Approaches for the Investigation of Arenavirus Biology and Development of Antiviral Strategies,http://dx.doi.org/10.1016/j.virol.2011.01.013,PMC3057228,,,"Several arenaviruses, chiefly Lassa virus, cause hemorrhagic fever disease in humans and pose a significant public health problem in their endemic regions. On the other hand the prototypic arenavirus LCMV is a superb workhorse for the investigation of virus-host interactions and associated disease. The development of novel antiviral strategies to combat pathogenic arenaviruses would be facilitated by a detailed understanding of the arenavirus molecular and cell biology. To this end, the development of reverse genetics systems for several arenaviruses has provided investigators with novel and powerful approaches to dissect the functions of arenavirus proteins and their interactions with host factors required to complete each of the steps of the virus life cycle, as well as to cause disease.",,"['Emonet, Sebastien E.', 'Urata, Shuzo', 'de la Torre, Juan C.']",,,,
,PMC,Highly Activated Cytotoxic CD8 T Cells Express Protective IL-10 At The Peak Of Coronavirus-induced Encephalitis,http://dx.doi.org/10.4049/jimmunol.1003292,PMC3063297,,,"Acute viral encephalitis requires rapid pathogen elimination without significant bystander tissue damage. Here, we show that IL-10, a potent anti-inflammatory cytokine, is produced transiently at the peak of infection by CD8 T cells in the brains of coronavirus-infected mice. IL-10(+)CD8 and IL-10(−)CD8 T cells interconvert during acute disease, possibly based on recent antigen exposure. Strikingly, IL-10(+)CD8 T cells were more highly activated and cytolytic than IL-10(−)CD8 T cells, expressing higher levels of proinflammatory cytokines and chemokines, as well as cytotoxic proteins. Even though these cells are highly proinflammatory, IL-10 expressed by these cells was functional. Further, IL-10 produced by CD8 T cells diminished disease severity in mice with coronavirus-induced acute encephalitis, suggesting a self-regulatory mechanism that minimizes immunopathological changes.",,"['Trandem, Kathryn', 'Zhao, Jingxian', 'Fleming, Erica', 'Perlman, Stanley']",,,,
,PMC,Cross-crystal averaging with search models to improve molecular replacement phases,http://dx.doi.org/10.1016/j.str.2010.12.007,PMC3037595,,,"The application of molecular replacement (MR) in macromolecular crystallography can be limited by the “model bias” problem. Here we propose a strategy to reduce model bias when only part of a new structure is known: after the MR search, structure determination of the unknown part of the new structure can be facilitated by cross-crystal averaging of the known part of the new structure with the search model. This strategy dramatically improves electron density in the unknown part of the new structure. It has enabled us to determine the structures of two coronavirus receptor-binding domains each complexed with their receptor at moderate resolutions. In a test case, it also enabled automated model building when over 50% of an antigen-antibody complex was absent. These results suggest that this averaging strategy can be routinely used after MR to enhance the interpretability of electron density associated with missing model.",,"['Li, Weikai', 'Li, Fang']",,,,
,PMC,Mice with human immune system components as in vivo models for infections with human pathogens,http://dx.doi.org/10.1038/icb.2010.151,PMC3087174,,,"Many pathogens relevant to human disease do not infect other animal species. Therefore, animal models that reconstitute or harbour human tissues are explored as hosts for these. In this review, we will summarize recent advances to utilize mice with human immune system components, reconstituted from hematopoietic progenitor cells in vivo. Such mice can be used to study human pathogens that replicate in leucocytes. In addition to studying the replication of these pathogens, the reconstituted human immune system components can also be analyzed for initiating immune responses and control against these infections. Moreover, these new animal models of human infectious disease should replicate the reactivity of the human immune system to vaccine candidates and, especially, the adjuvants contained in them, more faithfully.",,"['Rämer, Patrick C.', 'Chijioke, Obinna', 'Meixlsperger, Sonja', 'Leung, Carol S.', 'Münz, Christian']",,,,
,PMC,"Enantioselective syntheses of carbocyclic nuleosides 5′-homocarbovir, epi-4′-homocarbovir and their cyclopropylamine analogs using facially selective Pd-mediated allylations",http://dx.doi.org/10.1016/j.tet.2010.11.097,PMC3050557,,,"Carbocyclic nucleosides (−)-5′-homocarbovir and (+)-epi-4′-homocarbovir were prepared from an acylnitroso-derived hetero Diels–Alder cycloadduct. A kinetic enzymatic resolution generated an enantiopure aminocyclopentenol and Pd(0)-mediated decarboxylative allylations of allyl 2,2,2-trifluoroethyl malonates were used to install the 4′-hydroxyethyl groups. Late stage derivatization gave access to the cyclopropylamine congenors, (−)-5′-homoabacavir and (+)-epi-4′-homoabacavir. All carbonucleoside target molecules were evaluated for antiviral activity.",,"['Tardibono, Lawrence P.', 'Miller, Marvin J.', 'Balzarini, Jan']",,,,
,PMC,Integrating microRNAs into a system biology approach to acute lung injury,http://dx.doi.org/10.1016/j.trsl.2011.01.010,PMC3073780,,,"Acute lung injury (ALI), including the ventilator-induced lung injury (VILI) and the more severe acute respiratory distress syndrome (ARDS), are common and complex inflammatory lung diseases potentially affected by various genetic and non-genetic factors. Using the candidate gene approach, genetic variants associated with immune response and inflammatory pathways have been identified and implicated in ALI. Since gene expression is an intermediate phenotype that resides between DNA sequence variation and higher level cellular or whole-body phenotypes, the illustration of gene expression regulatory networks could potentially enhance understanding of disease susceptibility and the development of inflammatory lung syndromes. MicroRNAs (miRNAs) have emerged as a novel class of gene regulators which play critical roles in complex diseases including ALI. Comparisons of global miRNA profiles in animal models of ALI and VILI identified several miRNAs (e.g., miR-146a, miR-155) previously implicated in immune response and inflammatory pathways. Therefore, via regulation of target genes in these biological processes and pathways, miRNAs potentially contribute to the development of ALI. While this line of inquiry exists at a nascent stage, miRNAs have the potential to be critical components of a comprehensive model for inflammatory lung disease built by a systems biology approach that integrates genetic, genomic, proteomic, epigenetic as well environmental stimuli information. Given their particularly recognized role in regulation of immune and inflammatory responses, miRNAs also serve as novel therapeutic targets and biomarkers for ALI/ARDS or VILI, thus facilitating the realization of personalized medicine for individuals with acute inflammatory lung disease.",,"['Zhou, Tong', 'Garcia, Joe G.N.', 'Zhang, Wei']",,,,
,PMC,Complement and Viral Pathogenesis,http://dx.doi.org/10.1016/j.virol.2010.12.045,PMC3073741,,,"The complement system functions as an immune surveillance system that rapidly responds to infection. Activation of the complement system by specific recognition pathways triggers a protease cascade, generating cleavage products that function to eliminate pathogens, regulate inflammatory responses, and shape adaptive immune responses. However, when dysregulated, these powerful functions can become destructive and the complement system has been implicated as a pathogenic effector in numerous diseases, including infectious diseases. This review highlights recent discoveries that have identified critical roles for the complement system in the pathogenesis of viral infection.",,"['Stoermer, Kristina A.', 'Morrison, Thomas E.']",,,,
,PMC,Smokers Are Suckers: Should Incongruous Metaphors Be Used in Public Health Prevention?,http://dx.doi.org/10.2105/AJPH.2010.197996,PMC3020186,,,,,"['Basso, Frédéric', 'Oullier, Olivier']",,,,
,PMC,Viruses and Asthma,http://dx.doi.org/10.1016/j.bbagen.2011.01.012,PMC3130828,,,"BACKGROUND: Viral respiratory infection has long been known to influence the occurrence of asthma exacerbations. Over the last twenty years much effort has been put into clarifying the role that viral respiratory infections play in the eventual development of asthma. SCOPE OF REVIEW: In this review we give a general background of the role of viruses in the processes of asthma exacerbation and asthma induction. We review recent additions to the literature in the last three years with particular focus on clinical and epidemiologic investigations of influenza, rhinovirus, bocavirus, respiratory syncytial virus, and metapneumovirus. MAJOR CONCLUSIONS: The development of asthma emerges from a complex interaction of genetic predisposition and environmental factors with viral infection likely playing a significant role in the effect of environment on asthma inception. GENERAL SIGNIFICANCE: Further understanding of the role that viruses play in asthma exacerbation and inception will contribute to decreased asthma morbidity in the future.",,"['Dulek, Daniel E.', 'Peebles, R. Stokes']",,,,
,PMC,The integration of multiple HIV/AIDS projects into a coordinated national programme in China,http://dx.doi.org/10.2471/BLT.10.082552,PMC3044250,,,"External financial support from developed countries is a major resource for any developing country’s national AIDS programme. The influence of donors on the content and implementation of these programmes is thus inevitable. China is a large developing country that has received considerable international support for its HIV/AIDS programme. In the early stage of the response, each large HIV/AIDS project independently implemented their activities according to their project framework. When internationally funded projects were few and the quantity of domestic support was minimal, their independent implementation did not pose a problem. When many HIV/AIDS projects were simultaneously implemented in the same locations, problems emerged such as inconsistency and overlap in data collection. China has thus coordinated and integrated all large international and domestic HIV/AIDS projects into one national programme. The process of integration began slowly and initially consisted of unified data collection. Integration is now complete and encompasses the processes of project planning, budgeting, implementation, monitoring and evaluation. The process was facilitated by having a single coordinating body, cooperation from international agencies and financial commitment from the government. Some problems were encountered during this process, such as initial reluctance from health-care staff to allocate additional time to coordinate projects. This paper describes that process of integrating domestic and foreign HIV/AIDS projects and may serve as a useful example for other developing countries for management of scarce resources.",,"['Wu, Zunyou', 'Wang, Yu', 'Mao, Yurong', 'Sullivan, Sheena G', 'Juniper, Naomi', 'Bulterys, Marc']",,,,
,PMC,"An observational study on the prevalence and impact of Isospora suis in suckling piglets in southwestern Ontario, and risk factors for shedding oocysts",,PMC3022462,,,"An observational study was conducted to determine the prevalence of Isospora suis oocysts in fecal samples from suckling piglets in Ontario, and to evaluate the relationship between the presence of I. suis oocysts and diarrhea. Fifty farms and 709 litters of piglets were included in the study. Oocysts were detected on 70% of farms, with 187 litters infected. A litter of pigs that was positive for oocysts was significantly more likely to exhibit diarrhea than a litter that was negative [odds ratio (OR) = 4.0; 95% confidence interval (CI) = 2.8 to 5.8; P < 0.001]. Management and housing factors were examined with respect to risk factors for the presence of I. suis. Farms that did not use a detergent when cleaning farrowing crates were 10-times more likely to be positive for I. suis than those that used a detergent (P = 0.007). It was concluded that coccidiosis is a common problem on Ontario swine farms.",,"['Aliaga-Leyton, Andrea', 'Webster, Emma', 'Friendship, Robert', 'Dewey, Cate', 'Vilaça, Kevin', 'Peregrine, Andrew S.']",,,,
,PMC,The Serial Passage Theory of HIV Emergence,http://dx.doi.org/10.1093/cid/ciq166,PMC3106251,,,,,"['Marx, Preston A.', 'Drucker, Ernest M.', 'Schneider, William H.']",,,,
,PMC,Pneumocystis carinii Infection Causes Lung Lesions Historically Attributed to Rat Respiratory Virus,,PMC3060427,,,"Idiopathic lung lesions characterized by dense perivascular cuffs of lymphocytes and a lymphohistiocytic interstitial pneumonia have been noted in research rats since the 1990s. Although the etiology of this disease has remained elusive, a putative viral etiology was suspected and the term ‘rat respiratory virus’ (RRV) has been used in reference to this disease agent. The purpose of this study was to determine whether Pneumocystis carinii infection in immunocompetent rats can cause idiopathic lung lesions previously attributed to RRV. In archived paraffin-embedded lungs (n = 43), a significant association was seen between idiopathic lung lesions and Pneumocystis DNA detected by PCR. In experimental studies, lung lesions of RRV developed in 9 of 10 CD rats 5 wk after intratracheal inoculation with P. carinii. No lung lesions developed in CD rats (n = 10) dosed with a 0.22-µm filtrate of the P. carinii inoculum, thus ruling out viral etiologies, or in sham-inoculated rats (n = 6). Moreover, 13 of 16 CD rats cohoused with immunosuppressed rats inoculated with P. carinii developed characteristic lung lesions from 3 to 7 wk after cohousing, whereas no lesions developed in rats cohoused with immunosuppressed sham-inoculated rats (n = 7). Both experimental infection studies revealed a statistically significant association between lung lesion development and exposure to P. carinii. These data strongly support the conclusion that P. carinii infection in rats causes lung lesions that previously have been attributed to RRV.",,"['Livingston, Robert S', 'Besch-Williford, Cynthia L', 'Myles, Matthew H', 'Franklin, Craig L', 'Crim, Marcus J', 'Riley, Lela K']",,,,
,PMC,RT-PCR and Electrospray Ionization Mass Spectrometry (RT-PCR/ESI-MS) for Identifying Acute Viral Upper Respiratory Tract Infections,http://dx.doi.org/10.1016/j.diagmicrobio.2010.10.010,PMC3026598,,,"Diagnosis of respiratory viruses traditionally relies on culture or antigen detection.We aimed to demonstrate capacity of the RT-PCR/ESI-MS platform to identify clinical relevant respiratory viruses in nasopharyngeal aspirate (NPA) samples and compare the diagnostic performance characteristics relative to conventional culture- and antigen-based methods. A RT-PCR/ESI-MS respiratory virus surveillance kit designed to detect respiratory syncytial virus, influenza A and B, parainfluenza types 1-4, adenoviridae types A-F, coronaviridae, human bocavirus, and human metapneumovirus was evaluated using both mock-ups and frozen archived NPA (N=280), 95 of which were positive by clinical virology methods. RT-PCR/ESI-MS detected 74/95 (77.9%) known positive samples and identified an additional 13/185 (7%) from culture negative samples. Viruses that are non-detectable with conventional methods were also identified. Viral load was semi-quantifiable and ranged from 2,400 to >320,000copies/ml. Time to results was 8hrs. RT-PCR/ESI-MS showed promise in rapid detection of respiratory viruses, merits further evaluation for use in clinical settings.",,"['Chen, Kuan-Fu', 'Blyn, Lawrence', 'Rothman, Richard E.', 'Ramachandran, Padmini', 'Valsamakis, Alexandra', 'Ecker, David', 'Sampath, Rangarajan', 'Gaydos, Charlotte A.']",,,,
,PMC,Effects of Toll-like receptor signals in T-cell neoplasms,http://dx.doi.org/10.2217/fon.10.185,PMC3463000,,,"T-cell neoplasms have poor prognosis and few effective therapeutic options. Therefore, identification of factors in T-cell leukemia/lymphoma that are associated with cancer progression may represent novel therapeutic targets. Recent studies have highlighted a previously unappreciated role for the expression of Toll-like receptors (TLRs) on T cells and their effects on cell survival and proliferation. TLRs can bind exogenous molecules derived from pathogens as well as endogenous self-ligands released from damaged cells. Recent reports demonstrate that TLR engagement on primary mouse or human T cells enhances proliferation and/or cell survival. The mechanisms by which TLR stimulation on T cells influences these parameters and the different T-cell subsets that are affected by TLR stimulation are currently under investigation. Furthermore, neither the biological importance of stimulating TLRs on neoplastic T cells nor the prevalence of TLR expression in T-cell malignancies have yet to be characterized. Based on published reports and compelling preliminary data, we propose that the activation of the TLR-MyD88 signaling pathway in neoplastic T cells contributes to disease progression by reducing cell death and enhancing cell division. In this article, we present both theoretical arguments and experimental data in support of this hypothesis.",,"['Morrison, Cori', 'Baer, Maria R', 'Zandberg, Dan P', 'Kimball, Amy', 'Davila, Eduardo']",,,,
,PMC,Stressor-Induced Alterations of Adaptive Immunity to Vaccination and Viral Pathogens,http://dx.doi.org/10.1016/j.iac.2010.09.002,PMC3339561,,,,,"['Powell, Nicole D.', 'Allen, Rebecca G.', 'Hufnagle, Amy R.', 'Sheridan, John F.', 'Bailey, Michael T.']",,,,
,PMC,Introduction to the Symposium on Antimicrobial Therapy,http://dx.doi.org/10.4065/mcp.2011.0002,PMC3031431,,,,,"Temesgen, Zelalem",,,,
,PMC,Broad Humoral and Cellular Immunity Elicited by a Bivalent DNA Vaccine Encoding HA and NP Genes from an H5N1 Virus,http://dx.doi.org/10.1089/vim.2010.0056,PMC3034638,,,"Influenza A virus is highly variable and a major viral respiratory pathogen that can cause severe illness in humans. Therefore it is important to induce a sufficient immune response specific to current strains and to heterosubtypic viruses with vaccines. In this study, we developed a dual-promoter-based bivalent DNA vaccine that encodes both hemagglutinin (HA) and nucleoprotein (NP) proteins from a highly pathogenic A/Chicken/Henan/12/2004 (H5N1) virus. Our results show that the expression levels of HA and NP genes from the dual-promoter plasmid are similar to those seen when they are expressed individually in independent plasmids. When the bivalent DNA vaccine was inoculated via intramuscular injection and in vivo electroporation, high levels of both humoral and cellular immune responses were elicited against homologous H5N1 virus and heterosubtypic H9N2 virus. Furthermore, no obvious antigenic competition was observed between HA and NP proteins in the dual-promoter-based bivalent vaccine compared to monovalent vaccines. Our data suggest that a combination of influenza surface and internal viral genes in a dual-promoter-expressing plasmid may provide a new approach for developing a DNA vaccine that may protect not only specifically against a currently circulating strain, but also may cross-protect broadly against new heterosubtypic viruses.",,"['Xu, Ke', 'Ling, Zhi-Yang', 'Sun, Liang', 'Xu, Ying', 'Bian, Chao', 'He, Yuan', 'Lu, Wei', 'Chen, Ze', 'Sun, Bing']",,,,
,PMC,Generation and characterization of the human neutralizing antibody fragment Fab091 against rabies virus,http://dx.doi.org/10.1038/aps.2010.209,PMC4002766,,,"AIM: To transform the human anti-rabies virus glycoprotein (anti-RABVG) single-chain variable fragment (scFv) into a Fab fragment and to analyze its immunological activity. METHODS: The Fab gene was amplified using overlap PCR and inserted into the vector pComb3XSS. The recombinant vector was then transformed into E coli Top10F' for expression and purification. The purified Fab was characterized using SDS-PAGE, Western blotting, indirect ELISA, competitive ELISA, and the fluorescent antibody virus neutralization test (FAVN), respectively, and examined in a Kunming mouse challenge model in vivo. RESULTS: A recombinant vector was constructed. The Fab was expressed in soluble form in E coli Top10F'. Specific binding of the Fab to rabies virus was confirmed by indirect ELISA and immunoprecipitation (IP). The neutralizing antibody titer of Fab was 10.26 IU/mL. The mouse group treated with both vaccine and human rabies immunoglobulin (HRIG)/Fab091 (32 IU/kg) showed protection against rabies, compared with the control group (P<0.05, Logrank test). CONCLUSION: The antibody fragment Fab was shown to be a neutralizing antibody against RABVG. It can be used together with other monoclonal antibodies for post-exposure prophylaxis of rabies virus in future studies.",,"['Li, Chen', 'Zhang, Feng', 'Lin, Hong', 'Wang, Zhong-can', 'Liu, Xin-jian', 'Feng, Zhen-qing', 'Zhu, Jin', 'Guan, Xiao-hong']",,,,
,PMC,MCP-3/CCL7 production by astrocytes: Implications for SIV neuroinvasion and AIDS encephalitis,http://dx.doi.org/10.1007/s13365-010-0017-y,PMC3086688,,,"Monocyte/macrophages and activated lymphocytes traffic through normal brain, and this trafficking is increased in inflammatory conditions such as HIV encephalitis (HIVE). HIVE is characterized in part by perivascular accumulations of macrophages. The earliest events in this process are poorly understood and difficult or impossible to address in humans. The SIV-infected macaque model of neuroAIDS has demonstrated migration of monocytes into the brain early in disease, coincident with peak SIV viremia. The chemotactic signals that initiate the increased emigration of mononuclear cells into the CNS have not been described. Here we describe astrocytes as a primary source of chemokines to facilitate basal levels of monocyte trafficking to CNS and that increased CCL7 production may be responsible for initiating the increased trafficking in neuroAIDS. We have previously published complementary in vivo work demonstrating the presence of MCP-3/CCL7 within the brain of SIV-infected macaques. Here we demonstrate that MCP-3/CCL7 is a significant chemokine produced by astrocytes, that basal monocyte migration may be facilitated by astrocyte-derived CCL7, that production of CCL7 is rapidly increased by TNF and thus likely plays a critical role in initiating neuroinvasion by SIV/HIV.",,"['Renner, Nicole A.', 'Ivey, Nathan S.', 'Redmann, Rachel K.', 'Lackner, Andrew A.', 'MacLean, Andrew G.']",,,,
,PMC,Type III IFNs in Pteropid Bats: Differential Expression Patterns Provide Evidence for Distinct Roles in Antiviral Immunity,http://dx.doi.org/10.4049/jimmunol.1003115,PMC3057921,,,"Bats are known to harbor a number of emerging and re-emerging zoonotic viruses, many of which are highly pathogenic in other mammals but result in no clinical symptoms in bats. The ability of bats to coexist with viruses may be the result of rapid control of viral replication early in the immune response. IFNs provide the first line of defense against viral infection in vertebrates. Type III IFNs (IFN-λs) are a recently identified IFN family that share similar antiviral activities with type I IFNs. To our knowledge, we demonstrate the first functional analysis of type III IFNs from any species of bat, with the investigation of two IFN-λ genes from the pteropid bat, Pteropus alecto. Our results demonstrate that bat type III IFN has similar antiviral activity to type I and III IFNs from other mammals. In addition, the two bat type III IFNs are differentially induced relative to each other and to type I IFNs after treatment or transfection with synthetic dsRNA. Infection with the bat paramyxovirus, Tioman virus, resulted in no upregulation of type I IFN production in bat splenocytes but was capable of inducing a type III IFN response in three of the four bats tested. To our knowledge, this is the first report to describe the simultaneous suppression of type I IFN and induction of type III IFN after virus infection. These results may have important implications for the role of type III IFNs in the ability of bats to coexist with viruses.",,"['Zhou, Peng', 'Cowled, Chris', 'Todd, Shawn', 'Crameri, Gary', 'Virtue, Elena R.', 'Marsh, Glenn A.', 'Klein, Reuben', 'Shi, Zhengli', 'Wang, Lin-Fa', 'Baker, Michelle L.']",,,,
,PMC,Pathogen Inactivation of Platelet and Plasma Blood Components for Transfusion Using the INTERCEPT Blood System™,http://dx.doi.org/10.1159/000323937,PMC3132977,,,"BACKGROUND: The transmission of pathogens via blood transfusion is still a major threat. Expert conferences established the need for a pro-active approach and concluded that the introduction of a pathogen inactivation/reduction technology requires a thorough safety profile, a comprehensive pre-clinical and clinical development and an ongoing hemovigilance program. MATERIAL AND METHODS: The INTERCEPT Blood System utilizes amotosalen and UVA light and enables for the treatment of platelets and plasma in the same device. Preclinical studies of pathogen inactivation and toxicology and a thorough program of clinical studies have been conducted and an active he-movigilance-program established. RESULTS: INTERCEPT shows robust efficacy of inactivation for viruses, bacteria (including spirochetes), protozoa and leukocytes as well as large safety margins. Furthermore, it integrates well into routine blood center operations. The clinical study program demonstrates the successful use for very diverse patient groups. The hemovigilance program shows safety and tolerability in routine use. Approximately 700,000 INTERCEPT-treated products have been transfused worldwide. The system is in clinical use since class III CE-mark registration in 2002. The safety and efficacy has been shown in routine use and during an epidemic. CONCLUSION: The INTERCEPT Blood System for platelets and plasma offers enhanced safety for the patient and protection against transfusion-transmitted infections.",,"['Irsch, Johannes', 'Lin, Lily']",,,,
,PMC,Host factors and viral factors associated with severity of human rhinovirus infant respiratory illness,http://dx.doi.org/10.1016/j.jaci.2010.11.041,PMC3070861,,,"BACKGROUND: Risk factors for severe human rhinovirus (HRV) associated infant illness are unknown. OBJECTIVES: To examine the role of HRV in infant respiratory illness, and assess viral and host risk factors for HRV disease severity. METHODS: We utilized a prospective cohort of term, previously healthy infants enrolled during an inpatient or outpatient visit for acute upper or lower respiratory illness during fall-spring months 2004-2008. Illness severity was determined using an ordinal bronchiolitis severity score with higher scores indicating more severe disease. HRV was identified by real-time RT-PCR. The VP4/VP2 region from HRV positive specimens was sequenced to determine species. RESULTS: Of 630 infants with bronchiolitis or URI, 162 (26%) had HRV; HRV was associated with 18% of bronchiolitis and 47% of URI. Among infants with HRV, 104 (64%) had HRV alone. Host factors associated with more severe HRV illness included maternal and family history of atopy (median score 3.5, IQR [1.0-7.8] vs. 2.0 [1.0-5.2], and 3.5 [1.0-7.5] vs.2.0 [0-4.0]). In adjusted analyses maternal history of atopy conferred an increase in risk for more severe HRV bronchiolitis (OR=2.39, 95% CI:1.14-4.99, p=0.02). In a similar model, maternal asthma was also associated with greater HRV bronchiolitis severity (OR=2.49, 95% CI: 1.10-5.67, p=0.03). Among HRV, 35% were HRVA, 6% HRVB, and 30% HRVC. CONCLUSION: HRV was a frequent cause of bronchiolitis and URI among previously healthy term infants requiring hospitalization or unscheduled outpatient visits. Substantial genetic diversity was seen amongst the HRV, and predominant groups varied by season and year. Host factors including maternal atopy were associated with more severe infant HRV illness.",,"['Miller, E. Kathryn', 'Williams, John V.', 'Gebretsadik, Tebeb', 'Carroll, Kecia N.', 'Dupont, William D.', 'Mohamed, Yassir A.', 'Morin, Laura-Lee', 'Heil, Luke', 'Minton, Patricia A.', 'Woodward, Kimberly', 'Liu, Zhouwen', 'Hartert, Tina V.']",,,,
,PMC,Identification of a Small-Molecule Entry Inhibitor for Filoviruses,http://dx.doi.org/10.1128/JVI.01456-10,PMC3067866,,,"Ebola virus (EBOV) causes severe hemorrhagic fever, for which therapeutic options are not available. Preventing the entry of EBOV into host cells is an attractive antiviral strategy, which has been validated for HIV by the FDA approval of the anti-HIV drug enfuvirtide. To identify inhibitors of EBOV entry, the EBOV envelope glycoprotein (EBOV-GP) gene was used to generate pseudotype viruses for screening of chemical libraries. A benzodiazepine derivative (compound 7) was identified from a high-throughput screen (HTS) of small-molecule compound libraries utilizing the pseudotype virus. Compound 7 was validated as an inhibitor of infectious EBOV and Marburg virus (MARV) in cell-based assays, with 50% inhibitory concentrations (IC(50)s) of 10 μM and 12 μM, respectively. Time-of-addition and binding studies suggested that compound 7 binds to EBOV-GP at an early stage during EBOV infection. Preliminary Schrödinger SiteMap calculations, using a published EBOV-GP crystal structure in its prefusion conformation, suggested a hydrophobic pocket at or near the GP1 and GP2 interface as a suitable site for compound 7 binding. This prediction was supported by mutational analysis implying that residues Asn69, Leu70, Leu184, Ile185, Leu186, Lys190, and Lys191 are critical for the binding of compound 7 and its analogs with EBOV-GP. We hypothesize that compound 7 binds to this hydrophobic pocket and as a consequence inhibits EBOV infection of cells, but the details of the mechanism remain to be determined. In summary, we have identified a novel series of benzodiazepine compounds that are suitable for optimization as potential inhibitors of filoviral infection.",,"['Basu, Arnab', 'Li, Bing', 'Mills, Debra M.', 'Panchal, Rekha G.', 'Cardinale, Steven C.', 'Butler, Michelle M.', 'Peet, Norton P.', 'Majgier-Baranowska, Helena', 'Williams, John D.', 'Patel, Ishan', 'Moir, Donald T.', 'Bavari, Sina', 'Ray, Ranjit', 'Farzan, Michael R.', 'Rong, Lijun', 'Bowlin, Terry L.']",,,,
,PMC,"A chemotype that inhibits three unrelated pathogenic targets: the botulinum neurotoxin serotype A light chain, P. falciparum malaria, and the Ebola filovirus",http://dx.doi.org/10.1021/jm100938u,PMC3056319,,,"A 1,7-bis(alkylamino)diazachrysene-based small molecule was previously identified as an inhibitor of the botulinum neurotoxin serotype A light chain metalloprotease. Subsequently, a variety of derivatives of this chemotype were synthesized to develop structure-activity relationships, and all are inhibitors of the BoNT/A LC. Three-dimensional analyses indicated that half of the originally discovered 1,7-DAAC structure superimposed well with 4-amino-7-chloroquinoline-based antimalarial agents. This observation led to the discovery that several of the 1,7-DAAC derivatives are potent in vitro inhibitors of Plasmodium falciparum, and in general, are more efficacious against CQ-resistant strains than against CQ-susceptible strains. In addition, by inhibiting β-hematin formation, the most efficacious 1,7-DAAC-based antimalarials employ a mechanism of action analogous to that of 4,7-ACQ-based antimalarials, and are well tolerated by normal cells. One candidate was also effective when administered orally in a rodent-based malaria model. Finally, the 1,7-DAAC-based derivatives were examined for Ebola filovirus inhibition in an assay employing Vero76 cells, and three provided promising antiviral activities and acceptably low toxicities.",,"['Opsenica, Igor', 'Burnett, James C.', 'Gussio, Rick', 'Opsenica, Dejan', 'Todorović, Nina', 'Lanteri, Charlotte A.', 'Sciotti, Richard J.', 'Gettayacamin, Montip', 'Basilico, Nicoletta', 'Taramelli, Donatella', 'Nuss, Jonathan E.', 'Wanner, Laura', 'Panchal, Rekha G.', 'Šolaja, Bogdan A.', 'Bavari, Sina']",,,,
,PMC,Molecular basis for ubiquitin and ISG15 cross-reactivity in viral ovarian tumor domains,http://dx.doi.org/10.1073/pnas.1015287108,PMC3038727,,,"Crimean Congo hemorrhagic fever virus (CCHFV) is a deadly human pathogen that evades innate immune responses by efficiently interfering with antiviral signaling pathways mediated by NF-κB, IRF3, and IFNα/β. These pathways rely on protein ubiquitination for their activation, and one outcome is the modification of proteins with the ubiquitin (Ub)-like modifier interferon-stimulated gene (ISG)15. CCHFV and related viruses encode a deubiquitinase (DUB) of the ovarian tumor (OTU) family, which unlike eukaryotic OTU DUBs also targets ISG15 modifications. Here we characterized the viral OTU domain of CCHFV (vOTU) biochemically and structurally, revealing that it hydrolyzes four out of six tested Ub linkages, but lacks activity against linear and K29-linked Ub chains. vOTU cleaved Ub and ISG15 with similar kinetics, and we were able to understand vOTU cross-reactivity at the molecular level from crystal structures of vOTU in complex with Ub and ISG15. An N-terminal extension in vOTU not present in eukaryotic OTU binds to the hydrophobic Ile44 patch of Ub, which results in a dramatically different Ub orientation compared to a eukaryotic OTU–Ub complex. The C-terminal Ub-like fold of ISG15 (ISG15-C) adopts an equivalent binding orientation. Interestingly, ISG15-C contains an additional second hydrophobic surface that is specifically contacted by vOTU. These subtle differences in Ub/ISG15 binding allowed the design of vOTU variants specific for either Ub or ISG15, which will be useful tools to understand the relative contribution of ubiquitination vs. ISGylation in viral infection. Furthermore, the crystal structures will allow structure-based design of antiviral agents targeting this enzyme.",,"['Akutsu, Masato', 'Ye, Yu', 'Virdee, Satpal', 'Chin, Jason W.', 'Komander, David']",,,,
,PMC,"Delivery route, MyD88 signaling and cross-priming events determine the anti-tumor efficacy of an Adenovirus based melanoma vaccine",http://dx.doi.org/10.1016/j.vaccine.2011.01.022,PMC3058128,,,"Adenovirus (Ad)-based vaccines are considered for cancer immunotherapy, yet, detailed knowledge on their mechanism of action and optimal delivery route for anti-tumor efficacy is lacking. Here, we compared the anti-tumor efficacy of an Ad-based melanoma vaccine after intradermal, intravenous, intranasal or intraperitoneal delivery in the B16F10 melanoma model. The intradermal route induced superior systemic anti-melanoma immunity which was MyD88 signaling-dependent. Predominant transduction of non-professional antigen-presenting cells at the dermal vaccination sites and draining lymph nodes, suggested a role for cross-presentation, which was confirmed in vitro. We conclude that the dermis provides an optimal route of entry for Ad-based vaccines for high-efficacy systemic anti-tumor immunization and that this immunization likely involves cross-priming events in the draining lymph nodes.",,"['Hangalapura, Basav N', 'Oosterhoff, Dinja', 'Gupta, Tarun', 'de Groot, Jan', 'Wijnands, Pepijn GJTB', 'van Beusechem, Victor W.', 'den Haan, Joke', 'Tüting, Thomas', 'van den Eertwegh, Alfons JM', 'Curiel, David T', 'Scheper, Rik J', 'de Gruijl, Tanja D']",,,,
,PMC,Insights into cellular factors that regulate HIV-1 replication in human cells,http://dx.doi.org/10.1021/bi101805f,PMC3035746,,,"Retroviruses integrate into the host cell’s chromosome. Accordingly, many aspects of the life cycle of retroviruses like HIV-1 are intimately linked to the functions of cellular proteins and RNAs. In this review, we discuss in brief recent genome-wide screens for the identification of cellular proteins that assist HIV-1 replication in human cells. We also review findings on other cellular moieties that help or restrict the viral life cycle.",,"['Lever, Andrew ML', 'Jeang, Kuan-Teh']",,,,
,PMC,Structure of the Lassa virus nucleoprotein reveals a dsRNA-specific 3′ to 5′ exonuclease activity essential for immune suppression,http://dx.doi.org/10.1073/pnas.1016404108,PMC3038715,,,"Lassa fever virus, a member of the family Arenaviridae, is a highly endemic category A pathogen that causes 300,000–500,000 infections per year in Western Africa. The arenaviral nucleoprotein NP has been implicated in suppression of the host innate immune system, but the mechanism by which this occurs has remained elusive. Here we present the crystal structure at 1.5 Å of the immunosuppressive C-terminal portion of Lassa virus NP and illustrate that, unexpectedly, its 3D fold closely mimics that of the DEDDh family of exonucleases. Accompanying biochemical experiments illustrate that NP indeed has a previously unknown, bona fide exonuclease activity, with strict specificity for double-stranded RNA substrates. We further demonstrate that this exonuclease activity is essential for the ability of NP to suppress translocation of IFN regulatory factor 3 and block activation of the innate immune system. Thus, the nucleoprotein is a viral exonuclease with anti-immune activity, and this work provides a unique opportunity to combat arenaviral infections.",,"['Hastie, Kathryn M.', 'Kimberlin, Christopher R.', 'Zandonatti, Michelle A.', 'MacRae, Ian J.', 'Saphire, Erica Ollmann']",,,,
,PMC,Viral Etiology of Acute Febrile Respiratory Illnesses in Hospitalized Children Younger Than 24 Months,http://dx.doi.org/10.1177/0009922810394834,PMC3417762,,,"BACKGROUND: Respiratory infections are a leading cause of pediatric hospitalizations. This study investigated whether virus–virus or virus–Bordetella co-infections are more frequent or more severe than previously recognized. METHODS: This is a 3-year prospective study of children younger than 24 months hospitalized with a febrile respiratory illness. Viral pathogens were detected using multiplex polymerase chain reaction (PCR), enzyme-linked immunoassays, and/or viral cultures from nasopharyngeal samples. Bordetella infections were detected by PCR. RESULTS: A total of 201 patients were enrolled. Respiratory viruses were detected in 187 (93%) patients, with 52 (28%) multipathogen infections. The most common viruses detected were respiratory syncytial virus and rhinovirus/enterovirus. There were no differences in illness severity when comparing patients infected with one pathogen and those with multipathogen infection. CONCLUSION: Virus co-infection in young children hospitalized with an acute febrile respiratory infection is common but does not appear to be associated with illness severity.",,"['Suryadevara, Manika', 'Cummings, Erin', 'Bonville, Cynthia A.', 'Bartholoma, Nadine', 'Riddell, Scott', 'Kiska, Deanna', 'Rosenberg, Helene F.', 'Domachowske, Joseph B.']",,,,
,PMC,A Comparison of Two Methods for Retrieving ICD-9-CM data: The Effect of Using an Ontology-based Method for Handling Terminology Changes,http://dx.doi.org/10.1016/j.jbi.2011.01.005,PMC3440000,,,"OBJECTIVE: Most existing controlled terminologies can be characterized as collections of terms, wherein the terms are arranged in a simple list or organized in a hierarchy. These kinds of terminologies are considered useful for standardizing terms and encoding data and are currently used in many existing information systems. However, they suffer from a number of limitations that make data reuse difficult. Relatively recently, it has been proposed that formal ontological methods can be applied to some of the problems of terminological design. Biomedical ontologies organize concepts (embodiments of knowledge about biomedical reality) whereas terminologies organize terms (what is used to code patient data at a certain point in time, based on the particular terminology version). However, the application of these methods to existing terminologies is not straightforward. The use of these terminologies is firmly entrenched in many systems, and what might seem to be a simple option of replacing these terminologies is not possible. Moreover, these terminologies evolve over time in order to suit the needs of users. Any methodology must therefore take these constraints into consideration, hence the need for formal methods of managing changes. Along these lines, we have developed a formal representation of the concept-term relation, around which we have also developed a methodology for management of terminology changes. The objective of this study was to determine whether our methodology would result in improved retrieval of data. DESIGN: Comparison of two methods for retrieving data encoded with terms from the International Classification of Diseases (ICD-9-CM), based on their recall when retrieving data for ICD-9-CM terms whose codes had changed but which had retained their original meaning (code change). MEASUREMENTS: Recall and interclass correlation coefficient. RESULTS: Statistically significant differences were detected (p<0.05) with the McNemar test for two terms whose codes had changed. Furthermore, when all the cases are combined in an overall category, our method also performs statistically significantly better (p < 0.05). CONCLUSION: Our study shows that an ontology-based ICD-9-CM data retrieval method that takes into account the effects of terminology changes performs better on recall than one that does not in the retrieval of data for terms whose codes had changed but which retained their original meaning.",,"['Yu, Alexander C.', 'Cimino, James J.']",,,,
,PMC,The role of multifunctional M1 metallopeptidases in cell cycle progression,http://dx.doi.org/10.1093/aob/mcq265,PMC3091800,,,"BACKGROUND: Metallopeptidases of the M1 family are found in all phyla (except viruses) and are important in the cell cycle and normal growth and development. M1s often have spatiotemporal expression patterns which allow for strict regulation of activity. Mutations in the genes encoding M1s result in disease and are often lethal. This family of zinc metallopeptidases all share the catalytic region containing a signature amino acid exopeptidase (GXMXN) and a zinc binding (HEXXH[18X]E) motif. In addition, M1 aminopeptidases often also contain additional membrane association and/or protein interaction motifs. These protein interaction domains may function independently of M1 enzymatic activity and can contribute to multifunctionality of the proteins. SCOPE: A brief review of M1 metalloproteases in plants and animals and their roles in the cell cycle is presented. In animals, human puromycin-sensitive aminopeptidase (PSA) acts during mitosis and perhaps meiosis, while the insect homologue puromycin-sensitive aminopeptidase (PAM-1) is required for meiotic and mitotic exit; the remaining human M1 family members appear to play a direct or indirect role in mitosis/cell proliferation. In plants, meiotic prophase aminopeptidase 1 (MPA1) is essential for the first steps in meiosis, and aminopeptidase M1 (APM1) appears to be important in mitosis and cell division. CONCLUSIONS: M1 metalloprotease activity in the cell cycle is conserved across phyla. The activities of the multifunctional M1s, processing small peptides and peptide hormones and contributing to protein trafficking and signal transduction processes, either directly or indirectly impact on the cell cycle. Identification of peptide substrates and interacting protein partners is required to understand M1 function in fertility and normal growth and development in plants.",,"Peer, Wendy Ann",,,,
,PMC,Rapid Identification Viruses from Nasal Pharyngeal Aspirates in Acute Viral Respiratory Infections by RT-PCR and Electrospray Ionization Mass Spectrometry,http://dx.doi.org/10.1016/j.jviromet.2011.01.007,PMC3221309,,,"Diagnosis of the etiologic agent of respiratory viral infection relies traditionally on culture or antigen detection. This pilot was conducted evaluation comparing performance characteristics of the RT-PCR and Electrospray Ionization Mass Spectrometry (RT-PCR/ESI-MS) platform to conventional virological methods for identifying multiple clinically relevant respiratory viruses in nasopharyngeal aspirates. The RT-PCR/ESI-MS respiratory virus surveillance kit was designed to detect respiratory syncytial virus, influenza A and B, parainfluenza types 1-4, adenoviridae types A-F, coronaviridae, human bocavirus, and human metapneumovirus. Patients (N=192) attending an emergency department during the 2007-8 respiratory season consented, and “excess” frozen archived nasopharyngeal aspirates were analysed; 46 were positive by conventional virology and 69 by RT-PCR/ESI-MS, among which there were six samples with multiple viral pathogens detected. The sensitivity and specificity of the assay were 89.1% and 80.3%, respectively. Additional viruses that were not identified by conventional virology assays were detected (4 human bocaviruses and 7 coronaviruses). Samples in which the RT-PCR/ESI-MS results disagreed with conventional virology were sent for analysis by a third method using a commercial RT-PCR-based assay, which can identify viruses not detectable by conventional virologic procedures. Time to first result of RT-PCR/ESI-MS was 8 hours. RT-PCR/ESI-MS demonstrated capacity to detect respiratory viruses identifiable and unidentifiable by conventional methods rapidly.",,"['Chen, Kuan-Fu', 'Rothman, Richard E.', 'Ramachandran, Padmini', 'Blyn, Lawrence', 'Sampath, Rangarajan', 'Ecker, David', 'Valsamakis, Alexandra', 'Gaydos, Charlotte A.']",,,,
,PMC,"Heterologous immunity: immunopathology, autoimmunity and protection during viral infections",http://dx.doi.org/10.3109/08916934.2011.523277,PMC3633594,,,,,"['Selin, Liisa K.', 'Wlodarczyk, Myriam F', 'Kraft, Anke R.', 'Nie, Siwei', 'Kenney, Laurie L.', 'Puzone, Roberto', 'Celada, Franco']",,,,
,PMC,C-terminal tyrosine residues modulate the fusion activity of the Hendra virus fusion protein,http://dx.doi.org/10.1021/bi101597k,PMC3035738,,,"The paramyxovirus family includes important human pathogens such as measles, mumps, respiratory syncytial virus and the recently emerged, highly pathogenic Hendra and Nipah viruses. The viral fusion (F) protein plays critical roles in infection, promoting both the viral-cell membrane fusion events needed for viral entry as well as cell-cell fusion events leading to syncytia formation. We describe the surprising finding that addition of the short epitope HA tag to the cytoplasmic tail (CT) of the Hendra virus F protein leads to a significant increase in cell-cell membrane fusion. This increase was not due to alterations in surface expression, cleavage state, or association with lipid microdomains. Addition of a Myc tag of similar length did not alter Hendra F fusion activity, indicating that the observed stimulation was not solely a result of lengthening the CT. Three tyrosine residues within the HA tag were critical for the increase in fusion, suggesting C-terminal tyrosines may modulate Hendra fusion activity. The effects of HA tag addition varied with other fusion proteins, as parainfluenza virus 5 F-HA showed decreased surface expression and no stimulation in fusion. These results indicate that additions to the C-terminal end of the F protein CT can modulate protein function in a sequence specific manner, reinforcing the need for careful analysis of epitope tagged glycoproteins. In addition, our results implicate C-terminal tyrosine residues in modulation of the membrane fusion reaction promoted by these viral glycoproteins.",,"['Popa, Andreea', 'Pager, Cara Teresia', 'Dutch, Rebecca Ellis']",,,,
,PMC,Enterovirus Infections of the Central Nervous System Review,http://dx.doi.org/10.1016/j.virol.2010.12.014,PMC3060663,,,"Enteroviruses (EV) frequently infect the central nervous system (CNS) and induce neurological diseases. Although the CNS is composed of many different cell types, the spectrum of tropism for each EV is considerable. These viruses have the ability to completely shut down host translational machinery and are considered highly cytolytic, thereby causing cytopathic effects. Hence, CNS dysfunction following EV infection of neuronal or glial cells might be expected. Perhaps unexpectedly given their cytolytic nature, EVs may establish a persistent infection within the CNS, and the lasting effects on the host might be significant with unanticipated consequences. This review will describe the clinical aspects of EV-mediated disease, mechanisms of disease, determinants of tropism, immune activation within the CNS, and potential treatment regimes.",,"['Rhoades, Ross E.', 'Tabor-Godwin, Jenna M.', 'Tsueng, Ginger', 'Feuer, Ralph']",,,,
,PMC,Cyclophilin A (CyPA) Induces Chemotaxis Independent of Its Peptidylprolyl Cis-Trans Isomerase Activity: DIRECT BINDING BETWEEN CyPA AND THE ECTODOMAIN OF CD147,http://dx.doi.org/10.1074/jbc.C110.181347,PMC3048706,,,"Cyclophilin A (CyPA) is a ubiquitously distributed peptidylprolyl cis-trans isomerase (PPIase) that possesses diverse biological functions. Extracellular CyPA is a potent chemokine, which can directly induce leukocyte chemotaxis and contribute to the pathogenesis of inflammation-mediated diseases. Although it has been identified that the chemotaxis activity of CyPA is mediated through its cell surface signaling receptor CD147, the role of CyPA PPIase activity in this process is disputable, and the underlying molecular mechanism is still poorly understood. In this study, we present the first evidence that CyPA induces leukocyte chemotaxis through a direct binding with the ectodomain of CD147 (CD147(ECT)), independent of its PPIase activity. Although NMR study indicates that the CD147(ECT) binding site on CyPA overlaps with the PPIase active site, the PPIase inactive mutant CyPA(R55A) exhibits similar CD147(ECT) binding ability and chemotaxis activity to those of CyPA(WT). Furthermore, we have identified three key residues of CyPA involved in CD147(ECT) binding and found that mutations H70A, T107A, and R69A result in similar levels of reduction in CD147(ECT) binding ability and chemotaxis activity for CyPA, without affecting the PPIase activity. Our findings indicate that there exists a novel mechanism for CyPA to regulate cellular signaling processes, shedding new light on its applications in drug development and providing a new targeting site for drug design.",,"['Song, Fei', 'Zhang, Xin', 'Ren, Xiao-Bai', 'Zhu, Ping', 'Xu, Jing', 'Wang, Li', 'Li, Yi-Fei', 'Zhong, Nan', 'Ru, Qiang', 'Zhang, Da-Wei', 'Jiang, Jian-Li', 'Xia, Bin', 'Chen, Zhi-Nan']",,,,
,PMC,Structural basis for the removal of ubiquitin and interferon-stimulated gene 15 by a viral ovarian tumor domain-containing protease,http://dx.doi.org/10.1073/pnas.1013388108,PMC3038750,,,"The attachment of ubiquitin (Ub) and the Ub-like (Ubl) molecule interferon-stimulated gene 15 (ISG15) to cellular proteins mediates important innate antiviral responses. Ovarian tumor (OTU) domain proteases from nairoviruses and arteriviruses were recently found to remove these molecules from host proteins, which inhibits Ub and ISG15-dependent antiviral pathways. This contrasts with the Ub-specific activity of known eukaryotic OTU-domain proteases. Here we describe crystal structures of a viral OTU domain from the highly pathogenic Crimean–Congo haemorrhagic fever virus (CCHFV) bound to Ub and to ISG15 at 2.5-Å and 2.3-Å resolution, respectively. The complexes provide a unique structural example of ISG15 bound to another protein and reveal the molecular mechanism of an ISG15 cross-reactive deubiquitinase. To accommodate structural differences between Ub and ISG15, the viral protease binds the β-grasp folds of Ub and C-terminal Ub-like domain of ISG15 in an orientation that is rotated nearly 75° with respect to that observed for Ub bound to a representative eukaryotic OTU domain from yeast. Distinct structural determinants necessary for binding either substrate were identified and allowed the reengineering of the viral OTU protease into enzymes with increased substrate specificity, either for Ub or for ISG15. Our findings now provide the basis to determine in vivo the relative contributions of deubiquitination and deISGylation to viral immune evasion tactics, and a structural template of a promiscuous deubiquitinase from a haemorrhagic fever virus that can be targeted for inhibition using small-molecule-based strategies.",,"['James, Terrence W.', 'Frias-Staheli, Natalia', 'Bacik, John-Paul', 'Levingston Macleod, Jesica M.', 'Khajehpour, Mazdak', 'García-Sastre, Adolfo', 'Mark, Brian L.']",,,,
,PMC,The Use of Solvent/Detergent Treatment in Pathogen Reduction of Plasma,http://dx.doi.org/10.1159/000323552,PMC3132981,,,"The solvent/detergent (SD) process used for plasma can safely inactivate all lipid-enveloped viruses. The introduction of a specific prion-binding ligand gel in combination with SD treatment, time-reduced from 4 to 1-1.5 h, still ensures efficient virus kill, reduces abnormal prion protein by >5 log steps, and preserves levels of plasmin inhibitor at close to the reference range. Infections with known non-enveloped viruses such as HAV or parvovirus B19 are prevented by ensuring low virus loads in the starting plasma units, dilution through pooling of single plasma units, and neutralization of immune antibodies already present in the initial plasma pools. The major advantages of SD plasma over fresh frozen plasma and the other pathogen-inactivated plasmas are its extreme safety with respect to transfusion-related acute lung injury and the significantly lower likelihood of provoking allergic reactions. Both advantages are best interpreted as results of the dilution effect of pooling. No fewer than 18 clinical studies covering all indications for plasma, and extensive clinical experience have shown that reduced levels of coagulation factors and inhibitors as a result of SD treatment do not impair significantly the clinical efficacy or tolerance of plasma. Properly standardized clotting factor and inhibitor potencies and low batch-to-batch variations when compared with single-donor plasma units makes SD plasma more suitable for standardized treatment.",,"['Hellstern, Peter', 'Solheim, Bjarte G.']",,,,
,PMC,The Taking of the Cytoskeleton One Two Three: How Viruses Utilize the Cytoskeleton During Egress,http://dx.doi.org/10.1016/j.virol.2010.12.024,PMC3049855,,,The final assembly of nonlytic envelope viruses requires the coordinated transport of either subviral particles or fully formed virions to the plasma membrane for release from the cell. Recent research has delved into the mechanisms viruses employ to hijack the host cell’s cytoskeletal system for active transport to the site of final assembly and release. This review will look at recent findings that relate to the transport of virions to the cell periphery and out of the cell.,,"WARD, BRIAN M.",,,,
,PMC,Innate Immune Response to Influenza A Virus in Differentiated Human Alveolar Type II Cells,http://dx.doi.org/10.1165/rcmb.2010-0108OC,PMC3175576,,,"Alveolar Type II (ATII) cells are important targets for seasonal and pandemic influenza. To investigate the influenza-induced innate immune response in those cells, we measured the global gene expression profile of highly differentiated ATII cells infected with the influenza A virus at a multiplicity of infection of 0.5 at 4 hours and 24 hours after inoculation. Infection with influenza stimulated a significant increase in the mRNA concentrations of many host defense–related genes, including pattern/pathogen recognition receptors, IFN, and IFN-induced genes, chemokines, and suppressors of cytokine signaling. We verified these changes by quantitative real-time RT-PCR. At the protein level, we detected a robust virus-induced secretion of the three glutamic acid-leucine-arginine (ELR)-negative chemokines CXCL9, CXCL10, and CXCL11, according to ELISA. The ultraviolet inactivation of virus abolished the chemokine and cytokine response. Viral infection did not appear to alter the differentiation of ATII cells, as measured by cellular mRNA and concentrations of surfactant proteins. However, viral infection significantly reduced the secretion of surfactant protein (SP)–A and SP–D. In addition, influenza A virus triggered a time-dependent activation of phosphatidylinositol 3–kinase signaling in ATII cells. The inhibition of this pathway significantly decreased the release of infectious virus and the chemokine response, but did not alter virus-induced cell death. This study provides insights into influenza-induced innate immunity in differentiated human ATII cells, and demonstrates that the alveolar epithelium is a critical part of the initial innate immune response to influenza.",,"['Wang, Jieru', 'Nikrad, Mrinalini P.', 'Phang, Tzulip', 'Gao, Bifeng', 'Alford, Taylor', 'Ito, Yoko', 'Edeen, Karen', 'Travanty, Emily A.', 'Kosmider, Beata', 'Hartshorn, Kevan', 'Mason, Robert J.']",,,,
,PMC,Sore throat,,PMC3275136,,,"INTRODUCTION: About 10% of people present to primary healthcare services with sore throat each year. The causative organisms of sore throat may be bacteria (most commonly Streptococcus) or viruses (typically rhinovirus), although it is difficult to distinguish bacterial from viral infections clinically. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to reduce symptoms of acute infective sore throat? What are the effects of interventions to prevent complications of acute infective sore throat? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 8 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, corticosteroids, non-steroidal anti-inflammatory drugs, paracetamol, and probiotics.",,"Kenealy, Tim",,,,
,PMC,Rotavirus Replication Requires a Functional Proteasome for Effective Assembly of Viroplasms,http://dx.doi.org/10.1128/JVI.01631-10,PMC3067976,,,"The ubiquitin-proteasome system has been shown to play an important role in the replication cycle of different viruses. In this study, we describe a strong impairment of rotavirus replication upon inhibition of proteasomal activity. The effect was evidenced at the level of accumulation of viral proteins, viral RNA, and yield of infective particles. Kinetic studies revealed that the early steps of the replicative cycle following attachment, entry, and uncoating were clearly more sensitive to proteasome inhibition. We ruled out a direct inhibition of the viral polymerase activities and stability of viral proteins and found that the crucial step that was impaired by blocking proteasome activity was the assembly of new viroplasms. This was demonstrated by using chemical inhibitors of proteasome and by gene silencing using small interfering RNAs (siRNAs) specific for different proteasomal subunits and for the ubiquitin precursor RPS27A. In addition, we show that the effect of proteasome inhibition on virus infection is not due to increased levels of beta interferon (IFN-β).",,"['Contin, R.', 'Arnoldi, F.', 'Mano, M.', 'Burrone, O. R.']",,,,
,PMC,Successful Propagation of Flavivirus Infectious cDNAs by a Novel Method To Reduce the Cryptic Bacterial Promoter Activity of Virus Genomes,http://dx.doi.org/10.1128/JVI.01986-10,PMC3067970,,,"Reverse genetics is a powerful tool to study single-stranded RNA viruses. Despite tremendous efforts having been made to improve the methodology for constructing flavivirus cDNAs, the cause of toxicity of flavivirus cDNAs in bacteria remains unknown. Here we performed mutational analysis studies to identify Escherichia coli promoter (ECP) sequences within nucleotides (nt) 1 to 3000 of the dengue virus type 2 (DENV2) and Japanese encephalitis virus (JEV) genomes. Eight and four active ECPs were demonstrated within nt 1 to 3000 of the DENV2 and JEV genomes, respectively, using fusion constructs containing DENV2 or JEV segments and empty vector reporter gene Renilla luciferase. Full-length DENV2 and JEV cDNAs were obtained by inserting mutations reducing their ECP activity in bacteria without altering amino acid sequences. A severe cytopathic effect occurred when BHK21 cells were transfected with in vitro-transcribed RNAs from either a DENV2 cDNA clone with multiple silent mutations within the prM-E-NS1 region of dengue genome or a JEV cDNA clone with an A-to-C mutation at nt 90 of the JEV genome. The virions derived from the DENV2 or JEV cDNA clone exhibited infectivities similar to those of their parental viruses in C6/36 and BHK21 cells. A cis-acting element essential for virus replication was revealed by introducing silent mutations into the central portion (nt 160 to 243) of the core gene of DENV2 infectious cDNA or a subgenomic DENV2 replicon clone. This novel strategy of constructing DENV2 and JEV infectious clones could be applied to other flaviviruses or pathogenic RNA viruses to facilitate research in virology, viral pathogenesis, and vaccine development.",,"['Pu, Szu-Yuan', 'Wu, Ren-Huang', 'Yang, Chi-Chen', 'Jao, Tzu-Ming', 'Tsai, Ming-Han', 'Wang, Jing-Chyi', 'Lin, Hui-Mei', 'Chao, Yu-Sheng', 'Yueh, Andrew']",,,,
,PMC,Recombinant Sendai Viruses Expressing Fusion Proteins with Two Furin Cleavage Sites Mimic the Syncytial and Receptor-Independent Infection Properties of Respiratory Syncytial Virus,http://dx.doi.org/10.1128/JVI.02065-10,PMC3067931,,,"Cell entry by paramyxoviruses requires fusion between viral and cellular membranes. Paramyxovirus infection also gives rise to the formation of multinuclear, fused cells (syncytia). Both types of fusion are mediated by the viral fusion (F) protein, which requires proteolytic processing at a basic cleavage site in order to be active for fusion. In common with most paramyxoviruses, fusion mediated by Sendai virus F protein (F(SeV)) requires coexpression of the homologous attachment (hemagglutinin-neuraminidase [HN]) protein, which binds to cell surface sialic acid receptors. In contrast, respiratory syncytial virus fusion protein (F(RSV)) is capable of fusing membranes in the absence of the viral attachment (G) protein. Moreover, F(RSV) is unique among paramyxovirus fusion proteins since F(RSV) possesses two multibasic cleavage sites, which are separated by an intervening region of 27 amino acids. We have previously shown that insertion of both F(RSV) cleavage sites in F(SeV) decreases dependency on the HN attachment protein for syncytium formation in transfected cells. We now describe recombinant Sendai viruses (rSeV) that express mutant F proteins containing one or both F(RSV) cleavage sites. All cleavage-site mutant viruses displayed reduced thermostability, with double-cleavage-site mutants exhibiting a hyperfusogenic phenotype in infected cells. Furthermore, insertion of both F(RSV) cleavage sites in F(SeV) reduced dependency on the interaction of HN with sialic acid for infection, thus mimicking the unique ability of RSV to fuse and infect cells in the absence of a separate attachment protein.",,"['Rawling, Joanna', 'Cano, Olga', 'Garcin, Dominique', 'Kolakofsky, Daniel', 'Melero, José A.']",,,,
,PMC,Vesicular Stomatitis Virus as a Vector To Deliver Virus-Like Particles of Human Norovirus: a New Vaccine Candidate against an Important Noncultivable Virus,http://dx.doi.org/10.1128/JVI.02332-10,PMC3067930,,,"Human norovirus (HuNoV) is a major causative agent of food-borne gastroenteritis worldwide. Currently, there are no vaccines or effective therapeutic interventions for this virus. Development of an attenuated vaccine for HuNoV has been hampered by the inability to grow the virus in cell culture. Thus, a vector-based vaccine may be ideal. In this study, we constructed a recombinant vesicular stomatitis virus (rVSV-VP1) expressing VP1, the major capsid protein of HuNoV. Expression of the capsid protein by VSV resulted in the formation of HuNoV virus-like particles (VLPs) that are morphologically and antigenically similar to native virions. Recombinant rVSV-VP1 was attenuated in cultured mammalian cells as well as in mice. Mice inoculated with a single dose of rVSV-VP1 through intranasal and oral routes stimulated a significantly stronger humoral and cellular immune response than baculovirus-expressed VLP vaccination. Moreover, we demonstrated that mice inoculated with rVSV-VP1 triggered a comparable level of fecal and vaginal IgA antibody. Taken together, the VSV recombinant system not only provides a new approach to generate HuNoV VLPs in vitro but also a new avenue for the development of vectored vaccines against norovirus and other noncultivable viruses.",,"['Ma, Yuanmei', 'Li, Jianrong']",,,,
,PMC,Structural Analysis of a Viral Ovarian Tumor Domain Protease from the Crimean-Congo Hemorrhagic Fever Virus in Complex with Covalently Bonded Ubiquitin,http://dx.doi.org/10.1128/JVI.02496-10,PMC3067871,,,"Crimean-Congo hemorrhagic fever (CCHF) virus is a tick-borne, negative-sense, single-stranded RNA [ssRNA(−)] nairovirus that produces fever, prostration, and severe hemorrhages in humans. With fatality rates for CCHF ranging up to 70% based on several factors, CCHF is considered a dangerous emerging disease. Originally identified in the former Soviet Union and the Congo, CCHF has rapidly spread across large sections of Europe, Asia, and Africa. Recent reports have identified a viral homologue of the ovarian tumor protease superfamily (vOTU) within its L protein. This protease has subsequently been implicated in downregulation of the type I interferon immune response through cleavage of posttranslational modifying proteins ubiquitin (Ub) and the Ub-like interferon-simulated gene 15 (ISG15). Additionally, homologues of vOTU have been suggested to perform similar roles in the positive-sense, single-stranded RNA [ssRNA(+)] arteriviruses. By utilizing X-ray crystallographic techniques, the structure of vOTU covalently bound to ubiquitin propylamine, a suicide substrate of the enzyme, was elucidated to 1.7 Å, revealing unique structural elements that define this new subclass of the OTU superfamily. In addition, kinetic studies were carried out with aminomethylcoumarin (AMC) conjugates of monomeric Ub, ISG15, and NEDD8 (neural precursor cell expressed, developmentally downregulated 8) substrates in order to provide quantitative insights into vOTU's preference for Ub and Ub-like substrates.",,"['Capodagli, Glenn C.', 'McKercher, Marissa A.', 'Baker, Erica A.', 'Masters, Emily M.', 'Brunzelle, Joseph S.', 'Pegan, Scott D.']",,,,
,PMC,Structure and mechanism of Escherichia coli glutathionylspermidine amidase belonging to the family of cysteine; histidine-dependent amidohydrolases/peptidases,http://dx.doi.org/10.1002/pro.589,PMC3064834,,,"The bifunctional Escherichia coli glutathionylspermidine synthetase/amidase (GspSA) catalyzes both the synthesis and hydrolysis of Gsp. Its amidase domain (GspA), which catalyzes the hydrolysis of Gsp into glutathione and spermidine, plays an important role in redox sensing and protein S-thiolation. To gain insight of the regulation and catalytic mechanism of and further understand the recycling of the Gsp dimer and Gsp-S-protein adducts, we solved two crystal structures of GspA and GspSA both with the C59A mutation and bound with the substrate, Gsp. In both structures, Cys59, His131, and Glu147 form the catalytic triad, which is similar to other cysteine proteases. Comparison of the GspA_Gsp complex and apo GspSA structures indicates that on binding with Gsp, the side chains of Asn149 and Gln58 of the amidase domain are induced to move closer to the carbonyl oxygen of the cleaved amide bond of Gsp, thereby participating in catalysis. In addition, the helix-loop region of GspA, corresponding to the sequence (30)YSSLDPQEYEDDA(42), involves in regulating the substrate binding. Our previous study indicated that the thiol of Cys59 of GspA is only oxidized to sulfenic acid by H(2)O(2). When comparing the active site of GspA with those of other cysteine proteases, we found that limited space and hydrophobicity of the environment around Cys59 play an important role to inhibit its further oxidation. The structural results presented here not only elucidate the catalytic mechanism and regulation of GspA but also help us to design small molecules to inhibit or probe for the activity of GspA.",,"['Pai, Chien-Hua', 'Wu, Hsing-Ju', 'Lin, Chun-Hung', 'Wang, Andrew H-J']",,,,
,PMC,Pandemic Influenza: Implications for Preparation and Delivery of Critical Care Services,http://dx.doi.org/10.1177/0885066610393314,PMC4110744,,,"In a five week span during the 1918 influenza A pandemic, more than 2,000 patients were admitted to Cook County Hospital in Chicago with a diagnosis of either influenza or pneumonia; 642 patients, approximately 31% of those admitted, died with deaths occurring predominantly in patients twenty-five to thirty years of age.(1) This review summarizes basic information on the biology, epidemiology, control, treatment and prevention of influenza overall, and then addresses the potential impact of pandemic influenza in an Intensive Care Unit setting. Issues that require consideration include workforce staffing and safety, resource management, alternate sites of care surge of patients, altered standards of care and crisis communication.",,"['Manuell, Mary-Elise', 'Co, Mary Dawn T.', 'Ellison, Richard T.']",,,,
,PMC,Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5,http://dx.doi.org/10.1038/ni.1979,PMC3182538,,,"The 5′ cap structures of higher eukaryote mRNAs have ribose 2′-O-methylation. Likewise, many viruses that replicate in the cytoplasm of eukaryotes have evolved 2′-O-methyltransferases to autonomously modify their mRNAs. However, a defined biological role for 2′-O-methylation of mRNA remains elusive. Here we show that 2′-O-methylation of viral mRNA was critically involved in subverting the induction of type I interferon. We demonstrate that human and mouse coronavirus mutants lacking 2′-O-methyltransferase activity induced higher expression of type I interferon and were highly sensitive to type I interferon. Notably, the induction of type I interferon by viruses deficient in 2′-O-methyltransferase was dependent on the cytoplasmic RNA sensor Mda5. This link between Mda5-mediated sensing of viral RNA and 2′-O-methylation of mRNA suggests that RNA modifications such as 2′-O-methylation provide a molecular signature for the discrimination of self and non-self mRNA.",,"['Züst, Roland', 'Cervantes-Barragan, Luisa', 'Habjan, Matthias', 'Maier, Reinhard', 'Neuman, Benjamin W', 'Ziebuhr, John', 'Szretter, Kristy J', 'Baker, Susan C', 'Barchet, Winfried', 'Diamond, Michael S', 'Siddell, Stuart G', 'Ludewig, Burkhard', 'Thiel, Volker']",,,,
,PMC,Dependence of Golgi apparatus integrity on nitric oxide in vascular cells: implications in pulmonary arterial hypertension,http://dx.doi.org/10.1152/ajpheart.00767.2010,PMC3075042,,,"Although reduced bioavailability of nitric oxide (NO) has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH), its consequences on organellar structure and function within vascular cells is largely unexplored. We investigated the effect of reduced NO on the structure of the Golgi apparatus as assayed by giantin or GM130 immunofluorescence in human pulmonary arterial endothelial (HPAECs) and smooth muscle (HPASMCs) cells, bovine PAECs, and human EA.hy926 endothelial cells. Golgi structure was also investigated in cells in tissue sections of pulmonary vascular lesions in idiopathic PAH (IPAH) and in macaques infected with a chimeric simian immunodeficiency virus containing the human immunodeficiency virus (HIV)-nef gene (SHIV-nef) with subcellular three-dimensional (3D) immunoimaging. Compounds with NO scavenging activity including 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), methylene blue, N-acetylcysteine, and hemoglobin markedly fragmented the Golgi in all cell types evaluated as did monocrotaline pyrrole, while LY-83583, sildenafil, fasudil, Y-27632, Tiron, Tempol, or H(2)O(2) did not. Golgi fragmentation by NO scavengers was inhibited by diethylamine NONOate, was evident in HPAECs after selective knockdown of endothelial nitric oxide synthase using small interfering RNA (siRNA), was independent of microtubule organization, required the GTPase dynamin 2, and was accompanied by depletion of α-soluble N-ethylmaleimide-sensitive factor (NSF) acceptor protein (α-SNAP) from Golgi membranes and codispersal of the SNAP receptor (SNARE) Vti1a with giantin. Golgi fragmentation was confirmed in endothelial and smooth muscle cells in pulmonary arterial lesions in IPAH and the SHIV-nef-infected macaque with subcellular 3D immunoimaging. In SHIV-nef-infected macaques Golgi fragmentation was observed in cells containing HIV-nef-bearing endosomes. The observed Golgi fragmentation suggests that NO plays a significant role in modulating global protein trafficking patterns that contribute to changes in the cell surface landscape and functional signaling in vascular cells.",,"['Lee, Jason E.', 'Patel, Kirit', 'Almodóvar, Sharilyn', 'Tuder, Rubin M.', 'Flores, Sonia C.', 'Sehgal, Pravin B.']",,,,
,PMC,Addressing Institutional Amplifiers in the Dynamics and Control of Tuberculosis Epidemics,http://dx.doi.org/10.4269/ajtmh.2011.10-0472,PMC3005502,,,"Tuberculosis outbreaks originating in prisons, mines, or hospital wards can spread to the larger community. Recent proposals have targeted these high-transmission institutional amplifiers by improving case detection, treatment, or reducing the size of the exposed population. However, what effects these alternative proposals may have is unclear. We mathematically modeled these control strategies and found case detection and treatment methods insufficient in addressing epidemics involving common types of institutional amplifiers. Movement of persons in and out of amplifiers fundamentally altered the transmission dynamics of tuberculosis in a manner not effectively mitigated by detection or treatment alone. Policies increasing the population size exposed to amplifiers or the per-person duration of exposure within amplifiers potentially worsened incidence, even in settings with high rates of detection and treatment success. However, reducing the total population size entering institutional amplifiers significantly lowered tuberculosis incidence and the risk of propagating new drug-resistant tuberculosis strains.",,"['Basu, Sanjay', 'Stuckler, David', 'McKee, Martin']",,,,
,PMC,Two Conserved Residues Are Important for Inducing Highly Ordered Membrane Domains by the Transmembrane Domain of Influenza Hemagglutinin,http://dx.doi.org/10.1016/j.bpj.2010.11.014,PMC3010018,,,"The interaction with lipids of a synthetic peptide corresponding to the transmembrane domain of influenza hemagglutinin was investigated by means of electron spin resonance. A detailed analysis of the electron spin resonance spectra from spin-labeled phospholipids revealed that the major effect of the peptide on the dynamic membrane structure is to induce highly ordered membrane domains that are associated with electrostatic interactions between the peptide and negatively charged lipids. Two highly conserved residues in the peptide were identified as being important for the membrane ordering effect. Aggregation of large unilamellar vesicles induced by the peptide was also found to be correlated with the membrane ordering effect of the peptide, indicating that an increase in membrane ordering, i.e., membrane dehydration, is important for vesicle aggregation. The possibility that hydrophobic interaction between the highly ordered membrane domains plays a role in vesicle aggregation and viral fusion is discussed.",,"['Ge, Mingtao', 'Freed, Jack H.']",,,,
,PMC,"ACE2, a Promising Therapeutic Target for Pulmonary Hypertension",http://dx.doi.org/10.1016/j.coph.2010.12.002,PMC3075309,,,"Pulmonary arterial hypertension (PAH) is a chronic lung disease with poor diagnosis and limited therapeutic options. The current available therapies are ineffective in improving the quality of life and reducing mortality rates. There exists a clear unmet medical need to treat this disease, which necessitates the discovery of novel therapeutic targets/agents for safe and successful therapy. An altered renin-angiotensin system (RAS) has been implicated as a causative factor in the pathogenesis of PAH. Angiotensin II, a key effector peptide of the RAS, can exert deleterious effects on the pulmonary vasculature resulting in vasoconstriction, proliferation and inflammation, all of which contribute to PAH development. Recently, a new member of the RAS, Angiotensin converting enzyme 2 (ACE2), was discovered. This enzyme functions as a negative regulator of the angiotensin system by metabolizing Angiotensin II to a putative protective peptide, Angiotensin-(1-7). ACE2 is abundantly expressed in the lung tissue and emerging evidence suggests a beneficial role for this enzyme against lung diseases. In this review, we focus on ACE2 in relation to pulmonary hypertension and provide proof of principle for its therapeutic role in PAH.",,"['Shenoy, Vinayak', 'Qi, Yanfei', 'Katovich, Michael J', 'Raizada, Mohan K']",,,,
,PMC,Subcellular Localization and Rearrangement of Endoplasmic Reticulum by Brome Mosaic Virus Capsid Protein,http://dx.doi.org/10.1128/JVI.02020-10,PMC3067956,,,"Genome packaging in the plant-infecting Brome mosaic virus (BMV), a member of the alphavirus-like superfamily, as well as in other positive-strand RNA viruses pathogenic to humans (e.g., poliovirus) and animals (e.g., Flock House virus), is functionally coupled to replication. Although the subcellular localization site of BMV replication has been identified, that of the capsid protein (CP) has remained elusive. In this study, the application of immunofluorescence confocal microscopy to Nicotiana benthamiana leaves expressing replication-derived BMV CP as a green fluorescent protein (GFP) fusion, in conjunction with antibodies to the CP and double-stranded RNA, a presumed marker of RNA replication, revealed that the subcellular localization sites of replication and CP overlap. Our temporal analysis by transmission electron microscopy of ultrastructural modifications induced in BMV-infected N. benthamiana leaves revealed a reticulovesicular network of modified endoplasmic reticulum (ER) incorporating large assemblies of vesicles derived from ER accumulated in the cytoplasm during BMV infection. Additionally, for the first time, we have found by ectopic expression experiments that BMV CP itself has the intrinsic property of modifying ER to induce vesicles similar to those present in BMV infections. The significance of CP-induced vesicles in relation to CP-organized viral functions that are linked to replication-coupled packaging is discussed.",,"['Bamunusinghe, Devinka', 'Seo, Jang-Kyun', 'Rao, A. L. N.']",,,,
,PMC,CD8+ T Cell Immunity to 2009 Pandemic and Seasonal H1N1 Influenza Viruses,http://dx.doi.org/10.1016/j.vaccine.2010.12.073,PMC3061835,,,"A novel strain of H1N1 influenza A virus (pH1N1) emerged in 2009, causing a worldwide pandemic. Several studies suggest that this virus is antigenically more closely related to human influenza viruses that circulated prior to 1957 than viruses of more recent seasonal influenza varieties. The extent to which individuals who are naïve to the 2009 pH1N1 virus carry cross-reactive CD8+ T cells is not known, but a certain degree of reactivity would be expected since there is substantial conservation among the internal proteins of the virus. In the present study, we examined production of multiple cytokines in response to virus from CD8+ T cells in healthy adult subjects, between 18 and 50 years of age (born post 1957), who had no evidence of exposure to the 2009 pH1N1 virus, and had blood collected prior to the emergence of the pandemic in April of 2009. Human peripheral blood mononuclear cells (PBMC) were stimulated in vitro with a panel of live viruses, and assayed by intracellular cytokine staining and flow cytometry. Although results were variable, most subjects exhibited cytokine positive CD8+ T cells in response to pH1N1. Cytokine producing cells were predominantly single positive (IL2, IFNγ, or TNFα); triple-cytokine producing cells were relatively rare. This result suggests that although many adults carry cross-reactive T cells against the emergent pandemic virus, these cells are in a functionally limited state, possibly because these subjects have not had recent exposure to either seasonal or pandemic influenza strains.",,"['Scheible, Kristin', 'Zhang, Gang', 'Baer, Jane', 'Azadniv, Mitra', 'Lambert, Kris', 'Pryhuber, Gloria', 'Treanor, John J.', 'Topham, David J.']",,,,
,PMC,Dynamic Palmitoylation and the Role of DHHC Proteins in T Cell Activation and Anergy,http://dx.doi.org/10.1016/B978-0-12-387664-5.00001-7,PMC5464999,,,"Although protein S-palmitoylation was first characterized >30 years ago, and is implicated in the function, trafficking, and localization of many proteins, little is known about the regulation and physiological implications of this posttranslational modification. Palmitoylation of various signaling proteins required for TCR-induced T cell activation is also necessary for their proper function. LAT (linker for activation of T cells) is an essential scaffolding protein involved in T cell development and activation, and we found that its palmitoylation is selectively impaired in anergic T cells. The recent discovery of the DHHC family of palmitoyl acyl transferases (PATs) and the establishment of sensitive and quantitative proteomics-based methods for global analysis of the palmitoyl proteome led to significant progress in studying the biology and underlying mechanisms of cellular protein palmitoylation. We are using these approaches to explore the palmitoyl proteome in T lymphocytes and, specifically, the mechanistic basis for the impaired palmitoylation of LAT in anergic T cells. This chapter reviews the history of protein palmitoylation and its role in T cell activation, the DHHC family and new methodologies for global analysis of the palmitoyl proteome, and summarizes our recent work in this area. The new methodologies will accelerate the pace of research and provide a greatly improved mechanistic and molecular understanding of the complex process of protein palmitoylation and its regulation, and the substrate specificity of the novel DHHC family. Reversible protein palmitoylation will likely prove to be an important posttranslational mechanism that regulates cellular responses, similar to protein phosphorylation and ubiquitination.",,"['Ladygina, Nadejda', 'Martin, Brent R.', 'Altman, Amnon']",,,,
,PMC,Interaction of a Specific Population of Human Embryonic Stem Cell–Derived Progenitor Cells with CD11b+ Cells Ameliorates Sepsis-Induced Lung Inflammatory Injury,http://dx.doi.org/10.1016/j.ajpath.2010.09.041,PMC3069906,,,"Human embryonic stem cells differentiated under mesoderm-inducing conditions have important therapeutic properties in sepsis-induced lung injury in mice. Single cell suspensions obtained from day 7 human embryoid bodies (d7EBs) injected i.v. 1 hour after cecal ligation and puncture significantly reduced lung inflammation and edema as well as production of tumor necrosis factor-α and interferon-γ in lungs compared with controls, whereas interleukin-10 production remained elevated. d7EB cell transplantation also reduced mortality to 50% from 90% in the control group. The protection was ascribed to d7EB cell interaction with lung resident CD11b+ cells, and was correlated with the ability of d7EB cells to reduce it also reduced production of proinflammatory cytokines by CD11+ cells, and to endothelial NO synthase–derived NO by d7EB cells, leading to inhibition of inducible macrophage-type NO synthase activation in CD11b+ cells. The protective progenitor cells were positive for the endothelial and hematopoietic lineage marker angiotensin converting enzyme (ACE). Only the ACE+ fraction modulated the proinflammatory profile of CD11b+ cells and reduced mortality in septic mice. In contrast to the nonprotective ACE-cell fraction, the ACE+ cell fraction also produced NO. These findings suggest that an ACE+ subset of human embryonic stem cell–derived progenitor cells has a highly specialized anti-inflammatory function that ameliorates sepsis-induced lung inflammation and reduces mortality.",,"['Toya, Sophie P.', 'Li, Fei', 'Bonini, Marcelo G.', 'Gomez, Ignatius', 'Mao, Mao', 'Bachmaier, Kurt W.', 'Malik, Asrar B.']",,,,
,PMC,Natural Regulatory T Cells Control Coronary Arteriolar Endothelial Dysfunction in Hypertensive Mice,http://dx.doi.org/10.1016/j.ajpath.2010.11.034,PMC3069876,,,"Coronary artery disease in patients with hypertension is increasing worldwide and leads to severe cardiovascular complications. The cellular and molecular mechanisms that underlie this pathologic condition are not well understood. Experimental and clinical research indicates that immune cells and inflammation play a central role in the pathogenesis of cardiovascular diseases. Recently, it has been reported that CD4(+)CD25(+) regulatory T cells (Tregs) regulate heart fibrosis in hypertension. In this study, we determined the role of Tregs in coronary arteriolar endothelial dysfunction in angiotensin II–dependent hypertensive mice. Mice infused with angiotensin II had significantly increased blood pressure, as determined using telemetry, and apoptotic Treg numbers, as measured using flow cytometry. The mice displayed inflammation, assessed by macrophage activation/infiltration into coronary arterioles and the heart, and increased local tumor necrosis factor-α release, which participates in reduced coronary arteriolar endothelial-dependent relaxation in response to acetylcholine using an arteriograph. Hypertensive mice injected with Tregs isolated from control mice had significantly reduced macrophage activation and infiltration, reduced tumor necrosis factor-α release, and improved coronary arteriolar endothelium-dependent relaxation. Our novel data indicate that Tregs are important in the development of coronary arteriolar endothelial dysfunction in hypertension. These results suggest a new direction in the investigation of vascular disease in hypertension and could lead to a therapeutic strategy that involves immune system modulation using Tregs.",,"['Matrougui, Khalid', 'Zakaria, Abd Elmageed', 'Kassan, Modar', 'Choi, Sookyoung', 'Nair, Devika', 'Gonzalez-Villalobos, Romer A.', 'Chentoufi, Aziz A.', 'Kadowitz, Philip', 'Belmadani, Souad', 'Partyka, Megan']",,,,
,PMC,Plasmacytoid Dendritic Cells: Recent Progress and Open Questions,http://dx.doi.org/10.1146/annurev-immunol-031210-101345,PMC4160806,,,"Plasmacytoid dendritic cells (pDCs) are specialized in rapid and massive secretion of type I interferon (IFN-α/β) in response to foreign nucleic acids. Combined with their antigen presentation capacity, this powerful functionality enables pDCs to orchestrate innate and adaptive immune responses. pDCs combine features of both lymphocytes and classical dendritic cells and display unique molecular adaptations to nucleic acid sensing and IFN production. In the decade since the identification of the pDC as a distinct immune cell type, our understanding of its molecular underpinnings and role in immunity has progressed rapidly. Here we review select aspects of pDC biology including cell fate establishment and plasticity, specific molecular mechanisms of pDC function, and the role of pDCs in T cell responses, antiviral immunity, and autoimmune diseases. Important unresolved questions remain in these areas, promising exciting times in pDC research for years to come.",,"['Reizis, Boris', 'Bunin, Anna', 'Ghosh, Hiyaa S.', 'Lewis, Kanako L.', 'Sisirak, Vanja']",,,,
,PMC,Inhibition of primary effusion lymphoma engraftment in SCID mice by morpholino oligomers against early lytic genes of Kaposi’s sarcoma-associated herpesvirus,http://dx.doi.org/10.3851/IMP1810,PMC5630453,,,"BACKGROUND: Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with several malignant diseases, including Kaposi’s sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman’s disease. The objectives of this study were to explore peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) against KSHV early lytic genes and assess their efficacy in SCID mice against PEL engraftment. PPMOs are short single-stranded DNA analogs that contain a backbone of morpholine rings and phosphorodiamidate linkages and have high delivery efficiency into cells. METHODS: PEL cells were treated with PPMOs against viral interferon regulatory factor 1 (vIRF-1) and expression of vIRF-1 was analyzed. The PPMOs against vIRF-1 and viral interleukin 6 (vIL-6) were evaluated against PEL cell engraftment in SCID mice. The PPMOs were administered into peritoneal cavities of SCID mice for ten doses at two-day intervals. At week 3 and 9 after BCBL-1 delivery, peritoneal lavage was collected and the ratio of PEL cells among total cells was determined by flow cytometry analysis. RESULTS: Treatment of PEL cells with PPMOs against vIRF-1 led to reduction of vIRF-1 expression in a dose-dependent manner. Reduction of vIRF-1 expression resulted in higher levels of cellular IRF-3 and STAT1 (signal transducers and activators of transcription 1). SCID mice receiving a PPMO against vIL-6 had no engraftment of PEL cells and remained healthy throughout the 120-day study. CONCLUSION: This study showed that PPMOs can be effective antivirals against KSHV. Blocking expression of early lytic genes may lead to beneficial effect for control of KSHV-associated malignant diseases.",,"['Zhang, Yan-Jin', 'Patel, Deendayal', 'Nan, Yuchen', 'Fan, Sumin']",,,,
,PMC,Preventing and treating secondary bacterial infections with antiviral agents,http://dx.doi.org/10.3851/IMP1730,PMC4907367,,,"Bacterial super-infections contribute to the significant morbidity and mortality associated with influenza and other respiratory virus infections. There are robust animal model data but only limited clinical information on the effectiveness of licensed antiviral agents for the treatment of bacterial complications of influenza. The association of secondary bacterial pathogens with fatal pneumonia during the recent H1N1 influenza pandemic highlights the need for new development in this area. Basic and clinical research into viral-bacterial interactions over the last decade has revealed several mechanisms that underlie this synergism. By applying these insights to antiviral drug development, the potential exists to improve outcomes by means other than direct inhibition of the virus.",,"McCullers, Jonathan A.",,,,
,PMC,Viral Infections in Immunocompromised Patients,http://dx.doi.org/10.1016/j.bbmt.2010.11.008,PMC3030455,,,,,"['Englund, Janet', 'Feuchtinger, Tobias', 'Ljungman, Per']",,,,
,PMC,Acute cough in adults,,PMC3024161,,,,,"Worrall, Graham",,,,
,PMC,Exposure to infectious agents in dogs in remote coastal British Columbia: Possible sentinels of diseases in wildlife and humans,,PMC3003557,,,"Ranked among the top threats to conservation worldwide, infectious disease is of particular concern for wild canids because domestic dogs (Canis familiaris) may serve as sources and reservoirs of infection. On British Columbia’s largely undeveloped but rapidly changing central and north coasts, little is known about diseases in wolves (Canis lupus) or other wildlife. However, several threats exist for transfer of diseases among unvaccinated dogs and wolves. To gain baseline data on infectious agents in this area, including those with zoonotic potential, we collected blood and stool samples from 107 dogs in 5 remote communities in May and September 2007. Serology revealed that the dogs had been exposed to canine parvovirus, canine distemper virus, Bordetella bronchiseptica, canine respiratory coronavirus, and Leptospira interrogans. No dogs showed evidence of exposure to Ehrlichia canis, Anaplasma phagocytophilum, Borrelia burgdorferi, Dirofilaria immitis, or Cryptococcus gattii. Of 75 stool samples, 31 contained at least 1 parasitic infection, including Taeniid tapeworms, the nematodes Toxocara canis and Toxascaris leonina, and the protozoans Isospora sp., Giardia sp., Cryptosporidium sp., and Sarcocystis sp. This work provides a sound baseline for future monitoring of infectious agents that could affect dogs, sympatric wild canids, other wildlife, and humans.",,"['Bryan, Heather M.', 'Darimont, Chris T.', 'Paquet, Paul C.', 'Ellis, John A.', 'Goji, Noriko', 'Gouix, Maëlle', 'Smits, Judit E.']",,,,
,PMC,Isolation prevalence of pulmonary nontuberculous mycobacteria in Ontario in 2007,,PMC3071009,,,"BACKGROUND: The reported prevalence of pulmonary nontuberculous mycobacteria (NTM) infections is increasing. OBJECTIVE: To determine the ‘isolation prevalence’ of NTM in 2007 and compare it with previously published research that examined the increasing rates of isolation of NTM from clinical pulmonary specimens between 1997 and 2003. METHODS: Isolation prevalence was investigated retrospectively by reviewing a cohort of all positive pulmonary NTM culture results from the Tuberculosis and Mycobacteriology Laboratory, Public Health Laboratory (Toronto, Ontario) in 2007, which identifies at least 95% of NTM isolates in Ontario. Isolation prevalence was calculated as the number of persons with a pulmonary isolate in a calendar year divided by the contemporary population and expressed per 100,000 population. Changes in isolation prevalence from previous years were assessed for statistical significance using generalized linear models with a negative binomial distribution. RESULTS: In 2007, 4160 pulmonary isolates of NTM were collected from 2463 patients. The isolation prevalence of all species (excluding Mycobacterium gordonae) was 19 per 100,000 population in 2007 – an increase from previous observations reported for Ontario – corresponding to an average annual increase of 8.5% from 1997 to 2007 (P<0.0001). Average annual increases in isolation prevalence of Mycobacterium avium complex (8.8%, P<0.0001) and Mycobacterium xenopi (7.3%, P=0.0005) were largely responsible for the overall increase, while prevalence rates of rapidly growing mycobacteria remained relatively stable. CONCLUSION: The isolation prevalence of pulmonary NTM continues to increase significantly in Ontario, supporting the belief that pulmonary NTM disease is increasingly common.",,"['Al Houqani, Mohammed', 'Jamieson, Frances', 'Chedore, Pamela', 'Mehta, Mauli', 'May, Kevin', 'Marras, Theodore K']",,,,
,PMC,Getting high on traffic: The biochemistry of intracellular transport,http://dx.doi.org/10.4161/cl.1.1.14466,PMC3109462,,,"Molecular mechanisms of secretory and endocytic transport pathways were the focus of a recent ASBMB Special Symposium on Biochemistry of Membrane Traffic, held last October in the picturesque high-altitude setting of Lake Tahoe. An exciting and diverse array of research and discussion topics focused on recent advances in understanding the molecular basis of movement of protein and membrane through the eukaryotic secretory pathway. Highlights included discussions of the common structural and functional features of tethering complexes, the roles of the lipid PI 4P in the late secretory pathway, organization of specific ER sub-domains and a new look at Golgi biogenesis.",,"['Latham, Catherine F', 'Munson, Mary', 'Miller, Elizabeth A']",,,,
,PMC,The Airway Epithelium: Soldier in the Fight against Respiratory Viruses,http://dx.doi.org/10.1128/CMR.00014-10,PMC3021210,,,"Summary: The airway epithelium acts as a frontline defense against respiratory viruses, not only as a physical barrier and through the mucociliary apparatus but also through its immunological functions. It initiates multiple innate and adaptive immune mechanisms which are crucial for efficient antiviral responses. The interaction between respiratory viruses and airway epithelial cells results in production of antiviral substances, including type I and III interferons, lactoferrin, β-defensins, and nitric oxide, and also in production of cytokines and chemokines, which recruit inflammatory cells and influence adaptive immunity. These defense mechanisms usually result in rapid virus clearance. However, respiratory viruses elaborate strategies to evade antiviral mechanisms and immune responses. They may disrupt epithelial integrity through cytotoxic effects, increasing paracellular permeability and damaging epithelial repair mechanisms. In addition, they can interfere with immune responses by blocking interferon pathways and by subverting protective inflammatory responses toward detrimental ones. Finally, by inducing overt mucus secretion and mucostasis and by paving the way for bacterial infections, they favor lung damage and further impair host antiviral mechanisms.",,"['Vareille, Marjolaine', 'Kieninger, Elisabeth', 'Edwards, Michael R.', 'Regamey, Nicolas']",,,,
,PMC,A sensitive near-infrared fluorescent probe for caspase-mediated apoptosis: Synthesis and application in cell imaging,http://dx.doi.org/10.5582/ddt.2011.v5.5.220,PMC3265084,,,Near-infrared (NIR) absorbing dyes represent an intriguing avenue for extracting biological information from living subjects since they can be monitored with noninvasive optical imaging techniques. We designed and synthesized an imaging agent which contains a NIR fluorochrome (IR780) and peptidyl fluoromethyl ketone (FMK) for caspase-9 imaging of cells undergoing apoptosis. The IR780-FMK fluorescent probe had a Strokes shift of 79 nm and quantum yield 0.75. Prostate cancer DU145 cells undergoing apoptosis were successfully imaged using as little as 0.1 μM of IR780-FMK.,,"['Luan, Yepeng', 'Yang, Qiuhong', 'Xie, Yumei', 'Duan, Shaofeng', 'Cai, Shuang', 'Forrest, M.L']",,,,
,PMC,Progress in filovirus vaccine development: evaluating the potential for clinical use,http://dx.doi.org/10.1586/erv.10.152,PMC3398800,,,"Marburg and Ebola viruses cause severe hemorrhagic fever in humans and nonhuman primates. Currently, there are no effective treatments and no licensed vaccines; although a number of vaccine platforms have proven successful in animal models. The ideal filovirus vaccine candidate should be able to provide rapid protection following a single immunization, have the potential to work postexposure and be cross-reactive or multivalent against all Marburg virus strains and all relevant Ebola virus species and strains. Currently, there are multiple platforms that have provided prophylactic protection in nonhuman primates, including DNA, recombinant adenovirus serotype 5, recombinant human parainfluenza virus 3 and virus-like particles. In addition, a single platform, recombinant vesicular stomatitis virus, has demonstrated both prophylactic and postexposure protection in nonhuman primates. These results demonstrate that achieving a vaccine that is protective against filoviruses is possible; the challenge now is to prove its safety and efficacy in order to obtain a vaccine that is ready for human use.",,"['Falzarano, Darryl', 'Geisbert, Thomas W', 'Feldmann, Heinz']",,,,
,PMC,Stress Granules and Virus Replication,http://dx.doi.org/10.2217/fvl.11.108,PMC4574952,,,"Viruses are dependent on the cellular translation machinery for protein synthesis. Part of the innate immune response to infection is activation of the stress kinase PKR which phosphorylates the alpha subunit of the initiation factor eIF2. This results in inhibition of translation and is intended to block virus replication. A downstream effect of translational shutoff involves the formation of cytoplasmic granules, termed stress granules (SGs), that contain mRNAs, initiation factors, ribosomal subunits, and other mRNA regulatory proteins. SGs hold mRNAs in a translationally inactive state until cells recover from stress. Recent studies have begun to elucidate the impact of SGs on virus replication. Not surprisingly, viruses from diverse families have been found to modulate SG formation in infected cells by associating with important SG effecter proteins. This review describes the current knowledge on SGs and their interaction with and impact on virus replication.",,"Miller, Cathy L.",,,,
,PMC,Update of acute kidney injury: intensive care nephrology,,PMC3139681,,,"Albeit the considerable progress that has been made both in our understanding of the pathophysiology of acute renal failure (ARF) and in its treatment (continuous renal replacement therapies), the morbidity of this complex syndrome remains unacceptably high. The current review focuses on recent developments concerning the definition of ARF, new strategies for the prevention and pharmacological treatment of specific causes of ARF, dialysis treatment in the intensive care setting and provides an update on critical care issues relevant to the clinical nephrologist.",,"Tsagalis, G",,,,
,PMC,Experiences of nursing students in caring of patients in source isolation,,PMC3203293,22039374,CC BY-NC-SA,"BACKGROUND: Infectious disease control is one of the important components of patient care which can assist in reducing morbidity and mortality. Source isolation is one of the strategies that have used in order to prevent from the spread of contagious infectious diseases. Since nursing student should be able to do the caring in source isolation patients after learning the principles, it's necessary to assess the students’ perception of caring for this client group in order to prepare them for the role of caring. METHODS: This is a qualitative phenomenological study; its participants were selected with maximum variation by purposed sampling from first to fourth year nursing and midwifery students of Isfahan School of Nursing and Midwifery. The students used to do the patient caring during the clinical internship. The sampling done until 10 interview data saturation was obtained. In order to collect data, researcher used depth interview method. Data analysis was performed by seven-stage Collaizzi method. RESULTS: The findings of this study included 6 main concept (themes) from participants’ experiences as following: 1. Stressor agents of caring, 2. Response to stress, 3. Care requirments, 4. Care provider performance, 5. Consequence of care, and 6. Improper caring. CONCLUSIONS: Providing educational programs in terms of isolated patients can reduce anxiety in students which this can lead to more control and prevent the spread of infectious diseases. In addition, studying about patients’ needs can be useful for improving practical interventions and clinical care.",2011 Winter,"['Dehkordi, Leila Mardanian', 'Tavakol, Khosrow']",Iran J Nurs Midwifery Res,,,
,PMC,New Insights into the Role of RNase L in Innate Immunity,http://dx.doi.org/10.1089/jir.2010.0120,PMC3021357,,,"The interferon (IFN)-inducible 2′-5′-oligoadenylate synthetase (OAS)/RNase L pathway blocks infections by some types of viruses through cleavage of viral and cellular single-stranded RNA. Viruses induce type I IFNs that initiate signaling to the OAS genes. OAS proteins are pathogen recognition receptors for the viral pathogen-associated molecular pattern, double-stranded RNA. Double-stranded RNA activates OAS to produce p(x)5′A(2′p5′A)(n); x = 1–3; n > 2 (2-5A) from ATP. Upon binding 2-5A, RNase L is converted from an inactive monomer to a potently active dimeric endoribonuclease for single-stranded RNA. RNase L contains, from N- to C-terminus, a series of 9 ankyrin repeats, a linker, several protein kinase-like motifs, and a ribonuclease domain homologous to Ire1 (involved in the unfolded protein response). In the past few years, it has become increasingly apparent that RNase L and OAS contribute to innate immunity in many ways. For example, small RNA cleavage products produced by RNase L during viral infections can signal to the retinoic acid-inducible-I like receptors to amplify and perpetuate signaling to the IFN-β gene. In addition, RNase L is now implicated in protecting the central nervous system against viral-induced demyelination. A role in tumor suppression was inferred by mapping of the RNase L gene to the hereditary prostate cancer 1 (HPC1) gene, which in turn led to discovery of the xenotropic murine leukemia-related virus. A broader role in innate immunity is suggested by involvement of RNase L in cytokine induction and endosomal pathways that suppress bacterial infections. These newly described findings about RNase L could eventually provide the basis for developing broad-spectrum antimicrobial drugs.",,"['Chakrabarti, Arindam', 'Jha, Babal Kant', 'Silverman, Robert H.']",,,,
,PMC,Interferon-Stimulated Gene 15 and the Protein ISGylation System,http://dx.doi.org/10.1089/jir.2010.0110,PMC3021351,,,"Interferon-stimulated gene 15 (ISG15) is one of the most upregulated genes upon Type I interferon treatment or pathogen infection. Its 17 kDa protein product, ISG15, was the first ubiquitin-like modifier identified, and is similar to a ubiquitin linear dimer. As ISG15 modifies proteins in a similar manner to ubiquitylation, protein conjugation by ISG15 is termed ISGylation. Some of the primary enzymes that promote ISGylation are also involved in ubiquitin conjugation. The process to remove ISG15 from its conjugated proteins, termed de-ISGylation, is performed by a cellular ISG15-specific protease, ubiquitin-specific proteases with molecular mass 43 kDa (UBP43)/ubiquitin-specific proteases 18. Relative to ubiquitin, the biological function of ISG15 is still poorly understood, but ISG15 appears to play important roles in various biological and cellular functions. Therefore, there is growing interest in ISG15, as the study of free ISG15 and functional consequences of ISGylation/de-ISGylation may identify useful therapeutic targets. This review highlights recent discoveries and remaining questions important to understanding the biological functions of ISG15.",,"['Zhang, Dongxian', 'Zhang, Dong-Er']",,,,
,PMC,Development and Evaluation of Reverse Transcription Loop-Mediated Isothermal Amplification Assay for Rapid and Real-Time Detection of the Swine-Origin Influenza A H1N1 Virus,http://dx.doi.org/10.1016/j.jmoldx.2010.11.003,PMC3069812,,,"The recent emergence of the swine-origin influenza A H1N1 virus (S-OIV) poses a serious global health threat. Rapid detection and differentiation of S-OIV from seasonal influenza is crucial for patient management and control of the epidemics. A one-step, single-tube accelerated and quantitative S-OIV-specific H1 reverse transcription loop-mediated isothermal amplification (RTLAMP) assay for clinical diagnosis of S-OIV by targeting the H1 gene is reported in this article. A comparative evaluation of the H1-specific RTLAMP assay vis-à-vis the World Health Organization-approved real-time polymerase chain reaction (RTPCR), involving 239 acute-phase throat swab samples, demonstrated exceptionally higher sensitivity by picking up all of the 116 H1N1-positive cases and 36 additional positive cases among the negatives that were sequence-confirmed as S-OIV H1N1. None of the real-time RTPCR-positive samples were missed by the RTLAMP system. The comparative analysis revealed that S-OIV RTLAMP was up to tenfold more sensitive than the World Health Organization real-time RTPCR; it had a detection limit of 0.1 tissue culture infectious dosage of (50)/ml. One of the most attractive features of this isothermal gene amplification assay is that it seems to have an advantage in monitoring gene amplification by means of SYBR Green I dye-mediated naked-eye visualization within 30 minutes compared to 2 to 3 hours for a real-time reverse transcription polymerase chain reaction. This suggests that the RTLAMP assay is a valuable tool for rapid, real-time detection and quantification of S-OIV in acute-phase throat swab samples without requiring sophisticated equipment.",,"['Parida, Manmohan', 'Shukla, Jyoti', 'Sharma, Shashi', 'Ranghia Santhosh, Sanna', 'Ravi, Vasanthapuram', 'Mani, Reeta', 'Thomas, Maria', 'Khare, Shashi', 'Rai, Arvind', 'Kant Ratho, Radha', 'Pujari, Sujit', 'Mishra, Bijayanti', 'Lakshmana Rao, Putcha Venkata', 'Vijayaraghavan, Rajagopalan']",,,,
,PMC,A scientometric analysis of Indian research output in medicine during 1999–2008,http://dx.doi.org/10.4103/0976-9668.82313,PMC3312706,22470241,CC BY-NC-SA,"OBJECTIVE: This study analyzes the research activities of India in medicine during 1999–2008, based on the total publication output, its growth rate, quality of papers published and rank of India in the global context. Patterns of international collaborative research output and the major partner countries of India are also discussed. This study also evaluates the research performance of different types of Indian medical colleges, hospitals, research institutes, universities and research foundations and the characteristics of published literature in Indian and foreign journals. It also analyzes the medical research output by disease and organs. MATERIALS AND METHODS: The publication data on medicine has been retrieved by using SCOPUS database. RESULTS: India holds 12th rank among the productive countries in medicine research consisting of 65,745 papers with a global publication share of 1.59% and registering a growth rate of 76.68% for the papers published during 1999–2003 to 2004–2008. CONCLUSION: High quality research in India is grossly inadequate and requires strategic planning, investment and resource support. There is also a need to improve the existing medical education system, which should foster research culture.",2011 Jan-Jun,"['Gupta, B. M.', 'Bala, Adarsh']",J Nat Sci Biol Med,,,
,PMC,Noninvasive ventilation in acute respiratory failure due to H1N1 influenza,http://dx.doi.org/10.4103/0970-2113.76301,PMC3099510,21654986,CC BY,We present a case of severe H1N1 influenza with hypoxemic acute respiratory failure necessitating mechanical ventilation benefited from noninvasive positive pressure ventilation (NIPPV). The NIPPV may be of great use in treating patients with H1N1-related acute respiratory distress syndrome in a resource poor setting or when invasive ventilator is unavailable.,2011 Jan-Mar,"['Mohapatra, Prasanta R.', 'Dutt, Naveen', 'Khanduri, Sushant', 'Mishra, Baijayantimala', 'Janmeja, Ashok K.']",Lung India,,,
,PMC,Membrane-anchored serine proteases in health and disease,http://dx.doi.org/10.1016/B978-0-12-385504-6.00001-4,PMC3697097,,,"Serine proteases of the trypsin-like family have long been recognized to be critical effectors of biological processes as diverse as digestion, blood coagulation, fibrinolysis, and immunity. In recent years, a subgroup of these enzymes has been identified that are anchored directly to plasma membranes, either by a carboxy-terminal transmembrane domain (Type I), an amino-terminal transmembrane domain with a cytoplasmic extension (Type II or TTSP), or through a glycosyl-phosphatidylinositol (GPI) linkage. Recent biochemical, cellular, and in vivo analyses have now established that membrane-anchored serine proteases are key pericellular contributors to processes vital for development and the maintenance of homeostasis. This chapter will review our current knowledge of the biological and physiological functions of these proteases, their molecular substrates, and their contributions to disease.",,"['Antalis, Toni M.', 'Bugge, Thomas', 'Wu, Qingyu']",,,,
,PMC,Heuristic RNA pseudoknot prediction including intramolecular kissing hairpins,http://dx.doi.org/10.1261/rna.2394511,PMC3004063,,,"Pseudoknots are an essential feature of RNA tertiary structures. Simple H-type pseudoknots have been studied extensively in terms of biological functions, computational prediction, and energy models. Intramolecular kissing hairpins are a more complex and biologically important type of pseudoknot in which two hairpin loops form base pairs. They are hard to predict using free energy minimization due to high computational requirements. Heuristic methods that allow arbitrary pseudoknots strongly depend on the quality of energy parameters, which are not yet available for complex pseudoknots. We present an extension of the heuristic pseudoknot prediction algorithm DotKnot, which covers H-type pseudoknots and intramolecular kissing hairpins. Our framework allows for easy integration of advanced H-type pseudoknot energy models. For a test set of RNA sequences containing kissing hairpins and other types of pseudoknot structures, DotKnot outperforms competing methods from the literature. DotKnot is available as a web server under http://dotknot.csse.uwa.edu.au.",,"['Sperschneider, Jana', 'Datta, Amitava', 'Wise, Michael J.']",,,,
,PMC,Involvement of CD8+ T Cell-mediated Immune Responses in LcrV DNA Vaccine Induced Protection against Lethal Y. Pestis Challenge,http://dx.doi.org/10.1016/j.vaccine.2010.12.062,PMC3079781,,,"Yersinia pestis (Y. pestis) is the causative pathogen of plague, a highly fatal disease for which an effective vaccine, especially against mucosal transmission, is still not available. Like many bacterial infections, antigen-specific antibody responses have been traditionally considered critical, if not solely responsible, for vaccine-induced protection against Y. pestis. Studies in recent years have suggested the importance of T cell immune responses against Y. pestis infection but information is still limited about the details of Y. pestis antigen-specific T cell immune responses. In current report, studies are conducted to identify the presence of CD8+ T cell epitopes in LcrV protein, the leading antigen of plague vaccine development. Furthermore, depletion of CD8+ T cells in LcrV DNA vaccinated Balb/C mice led to reduced protection against lethal intranasal challenge of Y. pestis. These findings establish that an LcrV DNA vaccine is able to elicit CD8+ T cell immune responses against specific epitopes of this key plague antigen and that a CD8+ T cell immune response is involved in LcrV DNA vaccine-elicited protection. Future studies in plague vaccine development will need to examine if the presence of detectable T cell immune responses, in particular CD8+ T-cell immune responses, will enhance the protection against Y. pestis in higher animal species or humans.",,"['Wang, Shixia', 'Goguen, Jon D.', 'Li, Fusheng', 'Lu, Shan']",,,,
,PMC,Synthetic Biology: Putting Synthesis into Biology,http://dx.doi.org/10.1002/wsbm.104,PMC3057768,,,"The ability to manipulate living organisms is at the heart of a range of emerging technologies that serve to address important and current problems in environment, energy, and health. However, with all its complexity and interconnectivity, biology has for many years been recalcitrant to engineering manipulations. The recent advances in synthesis, analysis, and modeling methods have finally provided the tools necessary to manipulate living systems in meaningful ways, and have led to the coining of a field named synthetic biology. The scope of synthetic biology is as complicated as life itself – encompassing many branches of science, and across many scales of application. New DNA synthesis and assembly techniques have made routine the customization of very large DNA molecules. This in turn has allowed the incorporation of multiple genes and pathways. By coupling these with techniques that allow for the modeling and design of protein functions, scientists have now gained the tools to create completely novel biological machineries. Even the ultimate biological machinery – a self-replicating organism – is being pursued at this moment. It is the purpose of this review to dissect and organize these various components of synthetic biology into a coherent picture.",,"['Liang, Jing', 'Luo, Yunzi', 'Zhao, Huimin']",,,,
,PMC,N-Linked Glycosylation Facilitates Sialic Acid-Independent Attachment and Entry of Influenza A Viruses into Cells Expressing DC-SIGN or L-SIGN,http://dx.doi.org/10.1128/JVI.01705-10,PMC3067946,,,"It is widely recognized that sialic acid (SA) can mediate attachment of influenza virus to the cell surface, and yet the specific receptors that mediate virus entry are not known. For many viruses, a definitive demonstration of receptor function has been achieved when nonpermissive cells are rendered susceptible to infection following transfection of the gene encoding a putative receptor. For influenza virus, such approaches have been confounded by the abundance of SA on mammalian cells so that it has been difficult to identify cell lines that are not susceptible to infection. We examined influenza virus infection of Lec2 Chinese hamster ovary (CHO) cells, a mutant cell line deficient in SA. Lec2 CHO cells were resistant to influenza virus infection, and stable cell lines expressing either DC-SIGN or L-SIGN were generated to assess the potential of each molecule to function as SA-independent receptors for influenza A viruses. Virus strain BJx109 (H3N2) bound to Lec2 CHO cells expressing DC-SIGN or L-SIGN in a Ca(2+)-dependent manner, and transfected cells were susceptible to virus infection. Treatment of Lec2-DC-SIGN and Lec2-L-SIGN cells with mannan, but not bacterial neuraminidase, blocked infection, a finding consistent with SA-independent virus attachment and entry. Moreover, virus strain PR8 (H1N1) bears low levels of mannose-rich glycans and was inefficient at infecting Lec2 CHO cells expressing either DC-SIGN or L-SIGN, whereas other glycosylated H1N1 subtype viruses could infect cells efficiently. Together, these data indicate that human C-type lectins (DC-SIGN and L-SIGN) can mediate attachment and entry of influenza viruses independently of cell surface SA.",,"['Londrigan, Sarah L.', 'Turville, Stuart G.', 'Tate, Michelle D.', 'Deng, Yi-Mo', 'Brooks, Andrew G.', 'Reading, Patrick C.']",,,,
,PMC,North American Porcine Reproductive and Respiratory Syndrome Viruses Inhibit Type I Interferon Production by Plasmacytoid Dendritic Cells,http://dx.doi.org/10.1128/JVI.01616-10,PMC3067927,,,"Although enveloped viruses typically trigger the prodigious secretion of alpha interferon (IFN-α) by plasmacytoid dendritic cells (pDC), porcine pDC remain quiescent when exposed to porcine reproductive and respiratory syndrome virus (PRRSV). This inactivity is likely due to virus-mediated interference since the typical IFN-α response by either purified or nonsorted porcine pDC to transmissible gastroenteritis virus (TGEV) or the Toll-like receptor 9 agonist, oligodeoxynucleotide (ODN) D19, was markedly reduced in the presence of PRRSV. Suppression occurred independently of virus viability and acidification of pDC early endosomes but correlated with diminished levels of IFN-α mRNA. This change was attributed to an abrogation of transcription resulting from a decrease in the otherwise enhanced amounts of the requisite interferon regulatory factor 7 (IRF-7), whose gene expression in turn was limited as a consequence of a lessened availability of nuclear-localized signal transducer and activator of transcription 1 (STAT1). While PRRSV also inhibited tumor necrosis factor alpha (TNF-α) synthesis by pDC responding to either agent, only the interleukin-2 (IL-2) and IL-6 production instigated by ODN D19 exposure was blocked. Likewise, PRRSV did not impact a specific TGEV-associated enhancement of IL-8 expression. Moreover, an augmented phosphorylation of NF-κB seen in activated pDC was not only unaffected by PRRSV but actually occurred in its presence. Thus, as supported by a demonstrated resilience of pDC to PRRSV infection, this pathogen may interact with a cell surface protein(s) to selectively impede the completion of cascades involved in cytokine production by stimulated pDC.",,"['Calzada-Nova, Gabriela', 'Schnitzlein, William M.', 'Husmann, Robert J.', 'Zuckermann, Federico A.']",,,,
,PMC,Factors Supporting Intrathecal Humoral Responses following Viral Encephalomyelitis,http://dx.doi.org/10.1128/JVI.02260-10,PMC3067923,,,"Central nervous system (CNS) infections and autoimmune inflammatory disorders are often associated with retention of antibody-secreting cells (ASC). Although beneficial or detrimental contributions of ASC to CNS diseases remain to be defined, virus-specific ASC are crucial in controlling persistent CNS infection following coronavirus-induced encephalomyelitis. This report characterizes expression kinetics of factors associated with ASC homing, differentiation, and survival in the spinal cord, the prominent site of coronavirus persistence. Infection induced a vast, gamma interferon (IFN-γ)-dependent, prolonged increase in chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10, and CXCL11 mRNA, supporting a role for chemokine (C-X-C motif) receptor 3 (CXCR3)-mediated ASC recruitment. Similarly, CD4 T cell-secreted interleukin-21, a critical regulator of both peripheral activated B cells and CD8 T cells, was sustained during viral persistence. The ASC survival factors B cell-activating factor of the tumor necrosis factor (TNF) family (BAFF) and a proliferating-inducing ligand (APRIL) were also significantly elevated in the infected CNS, albeit delayed relative to the chemokines. Unlike IFN-γ-dependent BAFF upregulation, APRIL induction was IFN-γ independent. Moreover, both APRIL and BAFF were predominantly localized to astrocytes. Last, the expression kinetics of the APRIL and BAFF receptors coincided with CNS accumulation of ASC. Therefore, the factors associated with ASC migration, differentiation, and survival are all induced during acute viral encephalomyelitis, prior to ASC accumulation in the CNS. Importantly, the CNS expression kinetics implicate rapid establishment, and subsequent maintenance, of an environment capable of supporting differentiation and survival of protective antiviral ASC, recruited as plasmablasts from lymphoid organs.",,"['Phares, Timothy W.', 'Marques, Cristina P.', 'Stohlman, Stephen A.', 'Hinton, David R.', 'Bergmann, Cornelia C.']",,,,
,PMC,ACE2/ANG-(1–7)/Mas pathway in the brain: the axis of good,http://dx.doi.org/10.1152/ajpregu.00222.2010,PMC3075080,,,"The last decade has seen the discovery of several new components of the renin-angiotensin system (RAS). Among them, angiotensin converting enzyme-2 (ACE2) and the Mas receptor have forced a reevaluation of the original cascade and led to the emergence of a new arm of the RAS: the ACE2/ANG-(1–7)/Mas axis. Accordingly, the new system is now seen as a balance between a provasoconstrictor, profibrotic, progrowth axis (ACE/ANG-II/AT(1) receptor) and a provasodilatory, antifibrotic, antigrowth arm (ACE2/ANG-(1–7)/Mas receptor). Already, this simplistic vision is evolving and new components are branching out upstream [ANG-(1–12) and (pro)renin receptor] and downstream (angiotensin-IV and other angiotensin peptides) of the classical cascade. In this review, we will summarize the role of the ACE2/ANG-(1–7)/Mas receptor, focusing on the central nervous system with respect to cardiovascular diseases such as hypertension, chronic heart failure, and stroke, as well as neurological diseases. In addition, we will discuss the new pharmacological (antagonists, agonists, activators) and genomic (knockout and transgenic animals) tools that are currently available. Finally, we will review the latest data regarding the various signaling pathways downstream of the Mas receptor.",,"['Xu, Ping', 'Sriramula, Srinivas', 'Lazartigues, Eric']",,,,
,PMC,Targeting the neurovascular unit for treatment of neurological disorders,http://dx.doi.org/10.1016/j.pharmthera.2010.12.004,PMC3092634,,,"Drug discovery for CNS disorders has been restricted by the inability for therapeutic agents to cross the blood-brain barrier (BBB). Moreover, current drugs aim to correct neuron cell signaling, thereby neglecting pathophysiological changes affecting other cell types of the neurovascular unit (NVU). Components of the NVU (pericytes, microglia, astrocytes, and neurons, and basal lamina) act as an intricate network to maintain the neuronal homeostatic microenvironment. Consequently, disruptions to this intricate cell network lead to neuron malfunction and symptoms characteristic of CNS diseases. A lack of understanding in NVU signaling cascades may explain why current treatments for CNS diseases are not curative. Current therapies treat symptoms by maintaining neuron function. Refocusing drug discovery to sustain NVU function may provide a better method of treatment by promoting neuron survival. In this review, we will examine current therapeutics for common CNS diseases, describe the importance of the NVU in cerebral homeostasis and discuss new possible drug targets and technologies that aim to improve treatment and drug delivery to the diseased brain.",,"['VanGilder, Reyna L.', 'Rosen, Charles L.', 'Barr, Taura L.', 'Huber, Jason D.']",,,,
,PMC,Echinacea for treating the common cold: A randomized controlled trial,,PMC3056276,,,"BACKGROUND: Echinacea is widely used to treat common cold. OBJECTIVE: To assess potential benefits of echinacea as common cold treatment. DESIGN: Randomized controlled trial with four parallel groups: 1) no pills, 2) placebo pills (blinded), 3) echinacea pills (blinded), or 4) echinacea pills (open-label). (NCT00065715) SETTING: Community-based trial. PARTICIPANTS: People aged 12 to 80 years with new onset common cold. INTERVENTIONS: Extracts of Echinacea purpurea and E. angustifolia root were used to make tablets standardized to alkamide content. Indistinguishable placebo tablets contained only inert ingredients. MEASUREMENTS: The primary outcome was area-under-the-curve global severity, with severity assessed twice daily by self report on the Wisconsin Upper Respiratory Symptom Survey (WURSS-21). Secondary outcomes included interleukin-8 and neutrophil count from nasal wash assessed at intake and two days later. RESULTS: Of 719 enrolled, 713 completed the protocol. Participants were 64% female and 88% white, with mean age 33.7 years. Mean global severity was 236 and 258 for blinded and unblinded echinacea, 264 for blinded placebo, and 286 for those without pills. Contrasting the two blinded groups yields a 28 point (95% CI = −69 to 13) trend toward benefit for echinacea (p=0.089). Mean illness duration for the blinded and unblinded echinacea groups was 6.34 and 6.76 days, respectively, compared to 6.87 days for blinded placebo and 7.03 for no pills. Contrasting blinded groups yields a 0.53 day (95% CI = −1.25 to 0.19) trend toward benefit (p = 0.075). Median change interleukin-8 (pg/mL) and neutrophil cell count were: no pills (30, 1), blinded placebo (39, 1), blinded echinacea (58, 2), and open-label echinacea (70, 1), also not statistically significant. LIMITATIONS: Higher-than-expected variability limited power to detect small-but-potentially-important benefits. CONCLUSIONS: The observed shorter illness duration and lower severity seen in the echinacea groups were not statistically significant. These results do not support the ability of this dose of this echinacea formulation to substantively change the course of the common cold.",,"['Barrett, Bruce', 'Brown, Roger', 'Rakel, Dave', 'Mundt, Marlon', 'Bone, Kerry', 'Barlow, Shari', 'Ewers, Tola']",,,,
,PMC,Newcastle Disease Virus Expressing a Dendritic Cell-Targeted HIV Gag Protein Induces a Potent Gag-Specific Immune Response in Mice,http://dx.doi.org/10.1128/JVI.02036-10,PMC3067785,,,"Viral vaccine vectors have emerged as an attractive strategy for the development of a human immunodeficiency virus (HIV) vaccine. Recombinant Newcastle disease virus (rNDV) stands out as a vaccine vector since it has a proven safety profile in humans, it is a potent inducer of both alpha interferon (IFN-α) and IFN-β) production, and it is a potent inducer of dendritic cell (DC) maturation. Our group has previously generated an rNDV vector expressing a codon-optimized HIV Gag protein and demonstrated its ability to induce a Gag-specific CD8(+) T cell response in mice. In this report we demonstrate that the Gag-specific immune response can be further enhanced by the targeting of the rNDV-encoded HIV Gag antigen to DCs. Targeting of the HIV Gag antigen was achieved by the addition of a single-chain Fv (scFv) antibody specific for the DC-restricted antigen uptake receptor DEC205 such that the DEC205 scFv-Gag molecule was encoded for expression as a fusion protein. The vaccination of mice with rNDV coding for the DC-targeted Gag antigen induced an enhanced Gag-specific CD8(+) T cell response and enhanced numbers of CD4(+) T cells and CD8(+) T cells in the spleen relative to vaccination with rNDV coding for a nontargeted Gag antigen. Importantly, mice vaccinated with the DEC205-targeted vaccine were better protected from challenge with a recombinant vaccinia virus expressing the HIV Gag protein. Here we demonstrate that the targeting of the HIV Gag antigen to DCs via the DEC205 receptor enhances the ability of an rNDV vector to induce a potent antigen-specific immune response.",,"['Maamary, Jad', 'Array, Frida', 'Gao, Qinshan', 'García-Sastre, Adolfo', 'Steinman, Ralph M.', 'Palese, Peter', 'Nchinda, Godwin']",,,,
,PMC,Beyond the Consensus: Dissecting Within-Host Viral Population Diversity of Foot-and-Mouth Disease Virus by Using Next-Generation Genome Sequencing,http://dx.doi.org/10.1128/JVI.01396-10,PMC3067773,,,"The diverse sequences of viral populations within individual hosts are the starting material for selection and subsequent evolution of RNA viruses such as foot-and-mouth disease virus (FMDV). Using next-generation sequencing (NGS) performed on a Genome Analyzer platform (Illumina), this study compared the viral populations within two bovine epithelial samples (foot lesions) from a single animal with the inoculum used to initiate experimental infection. Genomic sequences were determined in duplicate sequencing runs, and the consensus sequence of the inoculum determined by NGS was identical to that previously determined using the Sanger method. However, NGS revealed the fine polymorphic substructure of the viral population, from nucleotide variants present at just below 50% frequency to those present at fractions of 1%. Some of the higher-frequency polymorphisms identified encoded changes within codons associated with heparan sulfate binding and were present in both foot lesions, revealing intermediate stages in the evolution of a tissue culture-adapted virus replicating within a mammalian host. We identified 2,622, 1,434, and 1,703 polymorphisms in the inoculum and in the two foot lesions, respectively: most of the substitutions occurred in only a small fraction of the population and represented the progeny from recent cellular replication prior to onset of any selective pressures. We estimated the upper limit for the genome-wide mutation rate of the virus within a cell to be 7.8 × 10(−4) per nucleotide. The greater depth of detection achieved by NGS demonstrates that this method is a powerful and valuable tool for the dissection of FMDV populations within hosts.",,"['Wright, Caroline F.', 'Morelli, Marco J.', 'Thébaud, Gaël', 'Knowles, Nick J.', 'Herzyk, Pawel', 'Paton, David J.', 'Haydon, Daniel T.', 'King, Donald P.']",,,,
,PMC,"Virus assembly, allostery, and antivirals",http://dx.doi.org/10.1016/j.tim.2010.11.003,PMC3026312,,,"Assembly of virus capsids and surface proteins must be regulated to ensure that the resulting complex is an infectious virion. Here we examine assembly of virus capsids, focusing on hepatitis B virus and bacteriophage MS2, and formation of glycoproteins in the alphaviruses. These systems are structurally and biochemically well-characterized and are simplest-case paradigms of self-assembly. Published data suggest that capsid and glycoprotein assembly is subject to allosteric regulation, that is, regulation at the level of conformational change. The hypothesis that allostery is a common theme in viruses suggests that deregulation of capsid and glycoprotein assembly by small molecule effectors will be an attractive antiviral strategy, as has been demonstrated with hepatitis B virus.",,"['Zlotnick, Adam', 'Mukhopadhyay, Suchetana']",,,,
,PMC,Targeting the ACE2-Ang-(1–7) Pathway in Cardiac Fibroblasts to Treat Cardiac Remodeling and Heart Failure,http://dx.doi.org/10.1016/j.yjmcc.2010.12.003,PMC3085048,,,"Fibroblasts play a pivotal role in cardiac remodeling and the development of heart failure through the deposition of extra-cellular matrix (ECM) proteins and also by affecting cardiomyocyte growth and function. The renin-angiotensin system (RAS) is a key regulator of the cardiovascular system in health and disease and many of its effects involve cardiac fibroblasts. Levels of angiotensin II (Ang II), the main effector molecule of the RAS, are elevated in the failing heart and there is a substantial body of evidence indicating that this peptide contributes to changes in cardiac structure and function which ultimately lead to progressive worsening in heart failure. A pathway involving angiotensin converting enzyme 2 (ACE2) has the capacity to break down Ang II while generating angiotensin-(1–7) (Ang-(1–7), a heptapeptide, which in contrast to Ang II, has cardioprotective and anti-remodeling effects. Many Ang-(1–7) actions involve cardiac fibroblasts and there is information indicating that it reduces collagen production and also may protect against cardiac hypertrophy. This report describes the effects of ACE2 and Ang-(1–7) that appear to be relevant in cardiac remodeling and heart failure and explores potential therapeutic strategies designed to increase ACE2 activity and Ang-(1–7) levels to treat these conditions.",,"['Iwata, Michikado', 'Cowling, Randy T.', 'Yeo, Seon Ju', 'Greenberg, Barry']",,,,
,PMC,A high-resolution human contact network for infectious disease transmission,http://dx.doi.org/10.1073/pnas.1009094108,PMC3009790,,,"The most frequent infectious diseases in humans—and those with the highest potential for rapid pandemic spread—are usually transmitted via droplets during close proximity interactions (CPIs). Despite the importance of this transmission route, very little is known about the dynamic patterns of CPIs. Using wireless sensor network technology, we obtained high-resolution data of CPIs during a typical day at an American high school, permitting the reconstruction of the social network relevant for infectious disease transmission. At 94% coverage, we collected 762,868 CPIs at a maximal distance of 3 m among 788 individuals. The data revealed a high-density network with typical small-world properties and a relatively homogeneous distribution of both interaction time and interaction partners among subjects. Computer simulations of the spread of an influenza-like disease on the weighted contact graph are in good agreement with absentee data during the most recent influenza season. Analysis of targeted immunization strategies suggested that contact network data are required to design strategies that are significantly more effective than random immunization. Immunization strategies based on contact network data were most effective at high vaccination coverage.",,"['Salathé, Marcel', 'Kazandjieva, Maria', 'Lee, Jung Woo', 'Levis, Philip', 'Feldman, Marcus W.', 'Jones, James H.']",,,,
,PMC,Parainfluenza Virus 5 M Protein Interaction with Host Protein 14-3-3 Negatively Affects Virus Particle Formation,http://dx.doi.org/10.1128/JVI.02111-10,PMC3067794,,,"Paramyxovirus matrix (M) proteins organize virus assembly, linking viral glycoproteins and viral ribonucleoproteins together at virus assembly sites on cellular membranes. Using a yeast two-hybrid screening approach, we identified 14-3-3 as a binding partner for the M protein of parainfluenza virus 5 (PIV5). Binding in both transfected and PIV5-infected cells was confirmed by coimmunoprecipitation and was mapped to a C-terminal region within the M protein, namely, 366-KTKSLP-371. This sequence resembles known 14-3-3 binding sites, in which the key residue for binding is a phosphorylated serine residue. Mutation of S369 within the PIV5 M protein disrupted 14-3-3 binding and improved the budding of both virus-like particles (VLPs) and recombinant viruses, suggesting that 14-3-3 binding impairs virus budding. 14-3-3 protein overexpression reduced the budding of VLPs. Using (33)P labeling, phosphorylated M protein was detected in PIV5-infected cells, and this phosphorylation was nearly absent in cells infected with a recombinant virus harboring an S369A mutation within the M protein. Assembly of the M protein into clusters and filaments at infected cell surfaces was enhanced in cells infected with a recombinant virus defective in 14-3-3 binding. These findings support a model in which a portion of M protein within PIV5-infected cells is phosphorylated at residue S369, binds the 14-3-3 protein, and is held away from sites of virus budding.",,"['Pei, Zifei', 'Harrison, Megan S.', 'Schmitt, Anthony P.']",,,,
,PMC,Pathogenesis of neurotropic murine coronavirus is multifactorial,http://dx.doi.org/10.1016/j.tips.2010.11.001,PMC3022387,,,"Although coronavirus tropism is most often ascribed to receptor availability, mounting evidence suggests that, for the neurotropic strains of the murine coronavirus mouse hepatitis virus (MHV), spike-receptor interactions cannot fully explain neurovirulence. The canonical MHV receptor CEACAM1a and its spike-binding site have been extensively characterized. However, CEACAM1a is poorly expressed in neurons, and the extremely neurotropic MHV strain JHM.SD infects ceacam1a−/− mice and spreads among ceacam1a−/− neurons. Two proposed alternative MHV receptors, CEACAM2 and PSG16, also fail to account for neuronal spread of JHM.SD in the absence of CEACAM1a. JHM.SD has been reported to have an unusually labile spike protein, enabling it to perform receptor-independent spread (RIS), but it is not clear that the ability to perform RIS is fully responsible for the extremely neurovirulent phenotype. We propose that the extreme neurovirulence of JHM.SD is multifactorial and might include as-yet unidentified neuron-specific mechanisms of spread.",,"['Phillips, Judith M.', 'Weiss, Susan R.']",,,,
,PMC,Impact of the implementation of rest days in live bird markets on the dynamics of H5N1 highly pathogenic avian influenza,http://dx.doi.org/10.1098/rsif.2010.0510,PMC3119874,,,"Live bird markets (LBMs) act as a network ‘hub’ and potential reservoir of infection for domestic poultry. They may therefore be responsible for sustaining H5N1 highly pathogenic avian influenza (HPAI) virus circulation within the poultry sector, and thus a suitable target for implementing control strategies. We developed a stochastic transmission model to understand how market functioning impacts on the transmission dynamics. We then investigated the potential for rest days—periods during which markets are emptied and disinfected—to modulate the dynamics of H5N1 HPAI within the poultry sector using a stochastic meta-population model. Our results suggest that under plausible parameter scenarios, HPAI H5N1 could be sustained silently within LBMs with the time spent by poultry in markets and the frequency of introduction of new susceptible birds' dominant factors determining sustained silent spread. Compared with interventions applied in farms (i.e. stamping out, vaccination), our model shows that frequent rest days are an effective means to reduce HPAI transmission. Furthermore, our model predicts that full market closure would be only slightly more effective than rest days to reduce transmission. Strategies applied within markets could thus help to control transmission of the disease.",,"['Fournié, G.', 'Guitian, F. J.', 'Mangtani, P.', 'Ghani, A. C.']",,,,
,PMC,A structural analysis of M protein in coronavirus assembly and morphology,http://dx.doi.org/10.1016/j.jsb.2010.11.021,PMC4486061,,,"The M protein of coronavirus plays a central role in virus assembly, turning cellular membranes into workshops where virus and host factors come together to make new virus particles. We investigated how M structure and organization is related to virus shape and size using cryo-electron microscopy, tomography and statistical analysis. We present evidence that suggests M can adopt two conformations and that membrane curvature is regulated by one M conformer. Elongated M protein is associated with rigidity, clusters of spikes and a relatively narrow range of membrane curvature. In contrast, compact M protein is associated with flexibility and low spike density. Analysis of several types of virus-like particles and virions revealed that S protein, N protein and genomic RNA each help to regulate virion size and variation, presumably through interactions with M. These findings provide insight into how M protein functions to promote virus assembly.",,"['Neuman, Benjamin W.', 'Kiss, Gabriella', 'Kunding, Andreas H.', 'Bhella, David', 'Baksh, M. Fazil', 'Connelly, Stephen', 'Droese, Ben', 'Klaus, Joseph P.', 'Makino, Shinji', 'Sawicki, Stanley G.', 'Siddell, Stuart G.', 'Stamou, Dimitrios G.', 'Wilson, Ian A.', 'Kuhn, Peter', 'Buchmeier, Michael J.']",,,,
,PMC,Plasmacytoid Dendritic Cell Ablation Impacts Early Interferon Responses and Antiviral NK and CD8(+) T Cell Accrual,http://dx.doi.org/10.1016/j.immuni.2010.11.020,PMC3588567,,,"Plasmacytoid dendritic cells (pDCs) mediate type I interferon (IFN-I) responses to viruses that are recognized through the Toll-like receptor 7 (TLR7) or TLR9 signaling pathway. However, it is unclear how pDCs regulate the antiviral responses via innate and adaptive immune cells. We generated diphtheria toxin receptor transgenic mice to selectively deplete pDCs by administration of diphtheria toxin. pDC-depleted mice were challenged with viruses known to activate pDCs. In murine cytomegalovirus (MCMV) infection, pDC depletion reduced early IFN-I production and augmented viral burden facilitating the expansion of natural killer (NK) cells expressing the MCMV-specific receptor Ly49H. During vesicular stomatitis virus (VSV) infection, pDC depletion enhanced early viral replication and impaired the survival and accumulation of virus-specific cytotoxic T lymphocytes. We conclude that pDCs mediate early antiviral IFN-I responses and influence the accrual of virus-specific NK or CD8(+) T cells in a virus-dependent manner.",,"['Swiecki, Melissa', 'Gilfillan, Susan', 'Vermi, William', 'Wang, Yaming', 'Colonna, Marco']",,,,
,PMC,MULTIPRED2: a computational system for large-scale identification of peptides predicted to bind to HLA supertypes and alleles,http://dx.doi.org/10.1016/j.jim.2010.11.009,PMC3090484,,,"MULTIPRED2 is a computational system for facile prediction of peptide binding to multiple alleles belonging to human leukocyte antigen (HLA) class I and class II DR molecules. It enables prediction of peptide binding to products of individual HLA alleles, combination of alleles, or HLA supertypes. NetMHCpan and NetMHCIIpan are used as prediction engines. The 13 HLA Class I supertypes are A1, A2, A3, A24, B7, B8, B27, B44, B58, B62, C1, and C4. The 13 HLA Class II DR supertypes are DR1, DR3, DR4, DR6, DR7, DR8, DR9, DR11, DR12, DR13, DR14, DR15, and DR16. In total, MULTIPRED2 enables prediction of peptide binding to 1077 variants representing 26 HLA supertypes. MULTIPRED2 has visualization modules for mapping promiscuous T-cell epitopes as well as those regions of high target concentration – referred to as T-cell epitope hotspots. Novel graphic representations are employed to display the predicted binding peptides and immunological hotspots in an intuitive manner and also to provide a global view of results as heat maps. Another function of MULTIPRED2, which has direct relevance to vaccine design, is the calculation of population coverage. Currently it calculates population coverage in five major groups in North America. MULTIPRED2 is an important tool to complement wet-lab experimental methods for identification of T-cell epitopes. It is available at http://cvc.dfci.harvard.edu/multipred2/.",,"['Zhang, Guang Lan', 'DeLuca, David S.', 'Keskin, Derin B.', 'Chitkushev, Lou', 'Zlateva, Tanya', 'Lund, Ole', 'Reinherz, Ellis L.', 'Brusic, Vladimir']",,,,
,PMC,Comparative Analysis of National Legislation in Support of the Revised International Health Regulations: Potential Models for Implementation in the United States,http://dx.doi.org/10.2105/AJPH.2009.180414,PMC2978189,,,"In 2005, the World Health Organization adopted the revised International Health Regulations, or IHR (2005), to establish obligations for detecting and responding to public health emergencies of international concern. The success of the IHR (2005) rests on the ability of states to implement the objectives and to execute the regulations in a legal and politically acceptable manner. Implementation of the IHR (2005) may be challenging for federalist nations, where most public health regulatory power lies in local rather than in national governments. We examine the implementation strategies of 4 nations: Australia, Canada, Germany, and India. The methods currently being considered by these nations for executing the IHR (2005) are potentially applicable models for the United States to consider.",,"['Katz, Rebecca', 'Kornblet, Sarah']",,,,
,PMC,Pneumonia in the immunocompetent patient,http://dx.doi.org/10.1259/bjr/31200593,PMC3473604,,,"Pneumonia is an acute inflammation of the lower respiratory tract. Lower respiratory tract infection is a major cause of mortality worldwide. Pneumonia is most common at the extremes of life. Predisposing factors in children include an under-developed immune system together with other factors, such as malnutrition and over-crowding. In adults, tobacco smoking is the single most important preventable risk factor. The commonest infecting organisms in children are respiratory viruses and Streptoccocus pneumoniae. In adults, pneumonia can be broadly classified, on the basis of chest radiographic appearance, into lobar pneumonia, bronchopneumonia and pneumonia producing an interstitial pattern. Lobar pneumonia is most commonly associated with community acquired pneumonia, bronchopneumonia with hospital acquired infection and an interstitial pattern with the so called atypical pneumonias, which can be caused by viruses or organisms such as Mycoplasma pneumoniae. Most cases of pneumonia can be managed with chest radiographs as the only form of imaging, but CT can detect pneumonia not visible on the chest radiograph and may be of value, particularly in the hospital setting. Complications of pneumonia include pleural effusion, empyema and lung abscess. The chest radiograph may initially indicate an effusion but ultrasound is more sensitive, allows characterisation in some cases and can guide catheter placement for drainage. CT can also be used to characterise and estimate the extent of pleural disease. Most lung abscesses respond to medical therapy, with surgery and image guided catheter drainage serving as options for those cases who do not respond.",,"['Reynolds, J H', 'Mcdonald, G', 'Alton, H', 'Gordon, S B']",,,,
,PMC,Catheterization of Intestinal Loops in Ruminants Does Not Adversely Affect Loop Function,,PMC3002107,,,"Catheterized intestinal loops may be a valuable model to elucidate key components of the host response to various treatments within the small intestine of ruminants. We examined whether catheterizing ileal loops in sheep affected the overall health of animals and intestinal function, whether a bacterial treatment could be introduced into the loops through the catheters, and whether broad-spectrum antibiotics could sterilize the loops. Escherichia coli cells transformed to express the GFP gene were introduced readily into the loops through the catheters, and GFP E. coli cells were localized within the injected loops. Catheterized loops, interspaces, and intact ileum exhibited no abnormalities in tissue appearance or electrical resistance. Expression of the IFNγ, IL1α, IL4, IL6, IL12p40, IL18, TGFβ1, and TNFα cytokine genes did not differ significantly among the intact ileum, catheterized loops, and interspaces, nor did the expression of the gene for inducible nitric oxide synthase. Broad-spectrum antibiotics administered during surgery did not sterilize the loops or interspaces and did not substantively change the composition of the microbiota. However, antibiotics reduced the overall number of bacterial cells within the loop and the relative abundance of community constituents. We concluded that catheterization of intestinal loops did not adversely affect health or loop function in sheep. Furthermore, allowing animals to recover fully from surgery and to clear pharmaceuticals will remove any confounding effects due to these factors, making catheterized intestinal loops a feasible model for studying host responses in ruminants.",,"['Inglis, G Douglas', 'Kastelic, John P', 'Uwiera, Richard R E']",,,,
,PMC,The Vagaries Of Public Support For Government Actions In Case Of A Pandemic,http://dx.doi.org/10.1377/hlthaff.2010.0474,PMC3445335,,,"Government health measures in a pandemic are effective only with strong support and compliance from the public. A survey of 1,583 US adults early in the 2009 H1N1 (swine influenza) pandemic shows surprisingly mixed support for possible government efforts to control the spread of the disease, with strong support for more extreme measures such as closing borders and weak support for more basic, and potentially more effective, policies such as encouraging sick people to stay home from work. The results highlight challenges that public health officials and policy makers must address in formulating strategies to respond to a pandemic before a more severe outbreak occurs.",,"['Hilyard, Karen M.', 'Freimuth, Vicki S.', 'Musa, Donald', 'Kumar, Supriya', 'Quinn, Sandra Crouse']",,,,
,PMC,Induction of Caspase Activation and Cleavage of the Viral Nucleocapsid Protein in Different Cell Types during Crimean-Congo Hemorrhagic Fever Virus Infection,http://dx.doi.org/10.1074/jbc.M110.149369,PMC3030327,,,"Regulation of apoptosis during infection has been observed for several viral pathogens. Programmed cell death and regulation of apoptosis in response to a viral infection are important factors for host or virus survival. It is not known whether Crimean-Congo hemorrhagic fever virus (CCHFV) infection regulates the apoptosis process in vitro. This study for the first time suggests that CCHFV induces apoptosis, which may be dependent on caspase-3 activation. This study also shows that the coding sequence of the S segment of CCHFV contains a proteolytic cleavage site, DEVD, which is conserved in all CCHFV strains. By using different recombinant expression systems and site-directed mutagenesis, we demonstrated that this motif is subject to caspase cleavage. We also demonstrate that CCHFV nucleocapsid protein (NP) is cleaved into a 30-kDa fragment at the same time as caspase activity is induced during infection. Using caspase inhibitors and cells lacking caspase-3, we clearly demonstrate that the cleavage of NP is caspase-3-dependent. We also show that the inhibition of apoptosis induced progeny viral titers of ∼80–90%. Thus, caspase-3-dependent cleavage of NP may represent a host defense mechanism against lytic CCHFV infection. Taken together, these data suggest that the most abundant protein of CCHFV, which has several essential functions such as protection of viral RNA and participation in various processes in the replication cycle, can be subjected to cleavage by host cell caspases.",,"['Karlberg, Helen', 'Tan, Yee-Joo', 'Mirazimi, Ali']",,,,
,PMC,Extracorporeal Life Support for Pandemic Influenza: The Role of Extracorporeal Membrane Oxygenation in Pandemic Management,,PMC4680015,,,"The recent global threat of a severe pandemic influenza outbreak has suggested that extracorporeal life support will begin to play an evolving role in the care of critically ill influenza stricken patients. The highly communicable attributes of influenza could result in widespread infection and an associated increased need for advanced life support. Supply and demand equilibrium may be abruptly disrupted, and ethical decisions regarding the allocation of life saving resources will inevitably need to be made. Protocol oriented planning, research analysis, and advanced technologies are critical factors in averting catastrophe. This review article details the epidemiology, diagnostic techniques, and interventions for the influenza A virus, including H1N1.",,"['DeLaney, Ed', 'Smith, Michael J.', 'Harvey, Brian T.', 'Pelletier, Keith J.', 'Aquino, Michael P.', 'Stone, Justin M.', 'Jean-Baptiste, Gerald C.', 'Johnson, Julie H.']",,,,
,PMC,Pathogenesis and Transmission of Triple-Reassortant Swine H1N1 Influenza Viruses Isolated before the 2009 H1N1 Pandemic,http://dx.doi.org/10.1128/JVI.02231-10,PMC3028905,,,"The 2009 H1N1 pandemic influenza virus represents the greatest incidence of human infection with an influenza virus of swine origin to date. Moreover, triple-reassortant swine (TRS) H1N1 viruses, which share similar host and lineage origins with 2009 H1N1 viruses, have been responsible for sporadic human cases since 2005. Similar to 2009 H1N1 viruses, TRS viruses are capable of causing severe disease in previously healthy individuals and frequently manifest with gastrointestinal symptoms; however, their ability to cause severe disease has not been extensively studied. Here, we evaluated the pathogenicity and transmissibility of two TRS viruses associated with disease in humans in the ferret model. TRS and 2009 H1N1 viruses exhibited comparable viral titers and histopathologies following virus infection and were similarly unable to transmit efficiently via respiratory droplets in the ferret model. Utilizing TRS and 2009 H1N1 viruses, we conducted extensive hematologic and blood serum analyses on infected ferrets to identify lymphohematopoietic parameters associated with mild to severe influenza virus infection. Following H1N1 or H5N1 influenza virus infection, ferrets were found to recapitulate several laboratory abnormalities previously documented with human disease, furthering the utility of the ferret model for the assessment of influenza virus pathogenicity.",,"['Belser, Jessica A.', 'Gustin, Kortney M.', 'Maines, Taronna R.', 'Blau, Dianna M.', 'Zaki, Sherif R.', 'Katz, Jacqueline M.', 'Tumpey, Terrence M.']",,,,
,PMC,Protein Expression Profiles Distinguish Between Experimental Invasive Pulmonary Aspergillosis and Pseudomonas Pneumonia,http://dx.doi.org/10.1002/pmic.200900768,PMC3859317,,,"We hypothesized that invasive pulmonary aspergillosis (IPA) may generate a distinctive proteomic signature in plasma and bronchoalveolar lavage (BAL). Proteins in plasma and BAL from two neutropenic rabbit models of IPA and Pseudomonas pneumonia were analyzed by SELDI-TOF MS. Hierarchical clustering analysis of plasma time course spectra demonstrated two clusters of peaks that were differentially regulated between IPA and Pseudomonas pneumonia (57 and 34 peaks, respectively, p<0.001). PCA of plasma proteins demonstrated a time-dependent separation of the two infections. A random forest analysis that ranked the top 30 spectral points distinguished between late Aspergillus and Pseudomonas pneumonias with 100% sensitivity and specificity. Based on spectral data analysis, three proteins were identified using SDS-PAGE and LC/MS and quantified using reverse phase arrays. Differences in the temporal sequence of plasma haptoglobin (p <0.001), apolipoprotein A1 (p<0.001) and transthyretin (p<0.038) were observed between IPA and Pseudomonas pneumonia, as was C-reactive protein (p<0.001). In summary, proteomic analysis of plasma and BAL proteins of experimental Aspergillus and Pseudomonas pneumonias demonstrates unique protein profiles with principal components and spectral regions that are shared in early infection and diverge at later stages of infection. Haptoglobin, apolipoprotein A1, transthyretin and C-reactive protein are differentially expressed in these infections suggesting important contributions to host defense against IPA.",,"['Gonzales, Denise A.', 'De Torre, Carlos', 'Wang, Honghui', 'Devor, Christopher B.', 'Munson, Peter J.', 'Ying, Sai-Xia', 'Kern, Steven J.', 'Petraitiene, Ruta', 'Levens, David L.', 'Walsh, Thomas J.', 'Suffredini, Anthony F.']",,,,
,PMC,A balance between circular and linear forms of the dengue virus genome is crucial for viral replication,http://dx.doi.org/10.1261/rna.2120410,PMC2995394,,,"The plasticity of viral plus strand RNA genomes is fundamental for the multiple functions of these molecules. Local and long-range RNA–RNA interactions provide the scaffold for interacting proteins of the translation, replication, and encapsidation machinery. Using dengue virus as a model, we investigated the relevance of the interplay between two alternative conformations of the viral genome during replication. Flaviviruses require long-range RNA–RNA interactions and genome cyclization for RNA synthesis. Here, we define a sequence present in the viral 3′UTR that overlaps two mutually exclusive structures. This sequence can form an extended duplex by long-range 5′-3′ interactions in the circular conformation of the RNA or fold locally into a small hairpin (sHP) in the linear form of the genome. A mutational analysis of the sHP structure revealed an absolute requirement of this element for viral viability, suggesting the need of a linear conformation of the genome. Viral RNA replication showed high vulnerability to changes that alter the balance between circular and linear forms of the RNA. Mutations that shift the equilibrium toward the circular or the linear conformation of the genome spontaneously revert to sequences with different mutations that tend to restore the relative stability of the two competing structures. We propose a model in which the viral genome exists in at least two alternative conformations and the balance between these two states is critical for infectivity.",,"['Villordo, Sergio M.', 'Alvarez, Diego E.', 'Gamarnik, Andrea V.']",,,,
,PMC,The Changing Face of Pediatric Respiratory Tract Infections: How Human Metapneumovirus and Human Bocavirus Fit into the Overall Etiology of Respiratory Tract Infections in Young Children,,PMC3002155,,,"Lower respiratory tract infections are one of the leading causes of morbidity and mortality in children worldwide. Recent technological advances in the field of molecular biology have allowed virologists to detect many previously undetected viral pathogens. Two of these, human metapneumovirus (hMPV) and human bocavirus (HBoV), are of particular clinical interest to pediatric health care providers. This review discusses the most common viral respiratory infections in children, explores the role of newly discovered respiratory pathogens, and describes techniques for the diagnosis of viral respiratory infections.",,"['Hustedt, Joshua W.', 'Vazquez, Marietta']",,,,
,PMC,Protein Microarrays: Novel Developments and Applications,http://dx.doi.org/10.1007/s11095-010-0325-1,PMC3137928,,,"Protein microarray technology possesses some of the greatest potential for providing direct information on protein function and potential drug targets. For example, functional protein microarrays are ideal tools suited for the mapping of biological pathways. They can be used to study most major types of interactions and enzymatic activities that take place in biochemical pathways and have been used for the analysis of simultaneous multiple biomolecular interactions involving protein-protein, protein-lipid, protein-DNA and protein-small molecule interactions. Because of this unique ability to analyze many kinds of molecular interactions en masse, the requirement of very small sample amount and the potential to be miniaturized and automated, protein microarrays are extremely well suited for protein profiling, drug discovery, drug target identification and clinical prognosis and diagnosis. The aim of this review is to summarize the most recent developments in the production, applications and analysis of protein microarrays.",,"['Berrade, Luis', 'Garcia, Angie E.', 'Camarero, Julio A.']",,,,
,PMC,Integrated Capillary Electrophoresis Microsystem for Multiplex Analysis of Human Respiratory Viruses,http://dx.doi.org/10.1021/ac1020744,PMC3076062,,,"We developed a two-layer, four-channel PCR-capillary electrophoresis microdevice that integrates nucleic acid amplification, sample cleanup and concentration, capillary electrophoretic separation and detection for multiplex analysis of four human respiratory viral pathogens influenza A, influenza B, coronavirus OC43, and human metapneumovirus. Biotinylated and fluorescently labeled double-stranded (ds) DNA amplification products are generated in a 100-nL PCR reactor incorporating an integrated heater and a temperature sensor. After amplification, the products are captured and concentrated in a crosslinked acrylamide gel capture matrix copolymerized with acrydite-functionalized streptavidin-capture agents. Thermal dehybridization releases the fluorescently labeled DNA strand for capillary electrophoresis injection, separation and detection. Using plasmid standards containing the viral genes of interest, each target can be detected starting from as few as 10 copies/reactor. By employing one-step reverse transcription PCR amplification, the device can detect RNA analogues of all four viral targets with detection limits in the range of 25–100 copies/reactor. The utility of the microdevice for analyzing samples from nasopharyngeal swabs is demonstrated. Combining size-based separation with four-color detection, this platform provides excellent product discrimination, making it readily extendable to higher-order multiplex assays. This portable microsystem is also suitable for performing automated assays in point-of-care diagnostic applications.",,"['Thaitrong, Numrin', 'Liu, Peng', 'Briese, Thomas', 'Lipkin, Ian', 'Chiesl, Thomas N.', 'Higa, Yukiko', 'Mathies, Richard A.']",,,,
,PMC,Global capacity for emerging infectious disease detection,http://dx.doi.org/10.1073/pnas.1006219107,PMC3003006,,,"The increasing number of emerging infectious disease events that have spread internationally, such as severe acute respiratory syndrome (SARS) and the 2009 pandemic A/H1N1, highlight the need for improvements in global outbreak surveillance. It is expected that the proliferation of Internet-based reports has resulted in greater communication and improved surveillance and reporting frameworks, especially with the revision of the World Health Organization's (WHO) International Health Regulations (IHR 2005), which went into force in 2007. However, there has been no global quantitative assessment of whether and how outbreak detection and communication processes have actually changed over time. In this study, we analyzed the entire WHO public record of Disease Outbreak News reports from 1996 to 2009 to characterize spatial-temporal trends in the timeliness of outbreak discovery and public communication about the outbreak relative to the estimated outbreak start date. Cox proportional hazards regression analyses show that overall, the timeliness of outbreak discovery improved by 7.3% [hazard ratio (HR) = 1.073, 95% CI (1.038; 1.110)] per year, and public communication improved by 6.2% [HR = 1.062, 95% CI (1.028; 1.096)] per year. However, the degree of improvement varied by geographic region; the only WHO region with statistically significant (α = 0.05) improvement in outbreak discovery was the Western Pacific region [HR = 1.102 per year, 95% CI (1.008; 1.205)], whereas the Eastern Mediterranean [HR = 1.201 per year, 95% CI (1.066; 1.353)] and Western Pacific regions [HR = 1.119 per year, 95% CI (1.025; 1.221)] showed improvement in public communication. These findings provide quantitative historical assessment of timeliness in infectious disease detection and public reporting of outbreaks.",,"['Chan, Emily H.', 'Brewer, Timothy F.', 'Madoff, Lawrence C.', 'Pollack, Marjorie P.', 'Sonricker, Amy L.', 'Keller, Mikaela', 'Freifeld, Clark C.', 'Blench, Michael', 'Mawudeku, Abla', 'Brownstein, John S.']",,,,
,PMC,Serum Cytokine Responses in Primary Pneumonic Plague Patients,http://dx.doi.org/10.1128/CVI.00386-10,PMC3019782,,,"The serum levels of interleukin-2 (IL-2), gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, and IL-10 of pneumonic plague patients were determined by enzyme-linked immunosorbent assay. IL-6 was the only elevated cytokine in the patients, and its level increased with a clear time course, indicating that IL-6 might be a prognostic marker for predicting the progression of plague.",,"['Wang, Xiaoyi', 'Wang, Zuyun', 'Guo, Zhaobiao', 'Wei, Baiqing', 'Tian, Fuzhang', 'Yu, Shouhong', 'Wang, Haoran', 'Wang, Hu', 'Yang, Ruifu']",,,,
,PMC,Modulation of Stress Granules and P Bodies during Dicistrovirus Infection,http://dx.doi.org/10.1128/JVI.02220-10,PMC3028890,,,"Stress granules (SGs) are dynamic cytosolic aggregates composed of ribonucleoproteins that are induced during cellular stress when protein synthesis is inhibited. The function of SGs is poorly understood, but they are thought to be sites for reorganizing mRNA and protein. Several viruses can modulate SG formation, suggesting that SGs have an impact on virus infection. In this study, we have investigated the relationship of SG formation in Drosophila S2 cells infected by cricket paralysis virus (CrPV), a member of the Dicistroviridae family. Despite a rapid shutoff of host translation during CrPV infection, several hallmark SG markers such as the Drosophila TIA-1 and G3BP (RasGAP-SH3-binding protein) homologs, Rox8 and Rin, respectively, do not aggregate in CrPV-infected cells, even when challenged with potent SG inducers such as heat shock, oxidative stress, and pateamine A treatment. Furthermore, we demonstrate that a subset of P body markers become moderately dispersed at late times of infection. In contrast, as shown by fluorescent in situ hybridization, poly(A)(+) RNA granules still form at late times of infection. These poly(A)(+) RNA granules do not contain viral RNA nor do they colocalize with P body markers. Finally, our results demonstrate that the CrPV viral 3C protease is sequestered to SGs under cellular stress but not during virus infection. In summary, we propose that dicistrovirus infection leads to the selective inhibition of distinct SGs so that viral proteins are available for viral processing.",,"['Khong, Anthony', 'Jan, Eric']",,,,
,PMC,Chronic Systemic Therapy With Low-dose Morpholino Oligomers Ameliorates the Pathology and Normalizes Locomotor Behavior in mdx Mice,http://dx.doi.org/10.1038/mt.2010.261,PMC3034854,,,"The administration of antisense oligonucleotides (AOs) to skip one or more exons in mutated forms of the DMD gene and so restore the reading frame of the transcript is one of the most promising approaches to treat Duchenne muscular dystrophy (DMD). At present, preclinical studies demonstrating the efficacy and safety of long-term AO administration have not been conducted. Furthermore, it is essential to determine the minimal effective dose and frequency of administration. In this study, two different low doses (LDs) of phosphorodiamidate morpholino oligomer (PMO) designed to skip the mutated exon 23 in the mdx dystrophic mouse were administered for up to 12 months. Mice treated for 50 weeks showed a substantial dose-related amelioration of the pathology, particularly in the diaphragm. Moreover, the generalized physical activity was profoundly enhanced compared to untreated mdx mice showing that widespread, albeit partial, dystrophin expression restores the normal activity in mdx mice. Our results show for the first time that a chronic long-term administration of LDs of unmodified PMO, equivalent to doses in use in DMD boys, is safe, significantly ameliorates the muscular dystrophic phenotype and improves the activity of dystrophin-deficient mice, thus encouraging the further clinical translation of this approach in humans.",,"['Malerba, Alberto', 'Sharp, Paul S', 'Graham, Ian R', 'Arechavala-Gomeza, Virginia', 'Foster, Keith', 'Muntoni, Francesco', 'Wells, Dominic J', 'Dickson, George']",,,,
,PMC,A high-throughput screening system for G-protein-coupled receptors using β-lactamase enzyme complementation technology,http://dx.doi.org/10.1038/aps.2010.154,PMC4002942,,,"AIM: To establish a system for monitoring the activation of G-protein-coupled receptors (GPCRs) using β-lactamase enzyme fragment complementation (EFC) technology. METHODS: Two inactive β-lactamase deletion fragments, bla(a) and bla(b), were fused to β-arrestin and GPCR, respectively. A stable cell line named HEK/293-β2a2, which expressed two fusion proteins, GPCR/bla(b) and β-arrestin2/bla(a), was generated under antibiotic selection. A natural compound library of high performance liquid chromatography (HPLC)-fractionated samples from the ethanol extracts of Chinese medicinal herbs was used for high-throughput screening (HTS) of β2-adrenoceptor (β2AR) agonists against the cell line HEK/293-β2a2. The interested hits were validated by the measurement of second-messenger cyclic adenosine monophosphate (cAMP) production. RESULTS: The stable cell line HEK/293-β2a2 responded to β2AR agonist/antagonist in a dose-dependent manner. The EC(50) value obtained for isoproterenol was 15.5 nmol/L, and the IC(50) value obtained for propranolol was 51.9 nmol/L. Furthermore, HTS was performed to identify β2AR agonists from the natural compound library we established. The Z′ factor value was determined to be 0.68. Three hits were identified from primary screening and found to be as potent as isoproterenol in a cAMP assay. CONCLUSION: A cell-based high-throughput functional assay was established to directly monitor the activation of GPCRs based on the interaction between agonist-activated GPCR and β-arrestin using β-lactamase EFC technology, which can be used to search for leads in the natural compound library.",,"['Zhao, Chuan-ke', 'Yin, Qi', 'Li, Shi-you']",,,,
,PMC,Caveolin-1: a critical regulator of lung injury,http://dx.doi.org/10.1152/ajplung.00170.2010,PMC4380484,,,"Caveolin-1 (cav-1), a 22-kDa transmembrane scaffolding protein, is the principal structural component of caveolae. Cav-1 regulates critical cell functions including proliferation, apoptosis, cell differentiation, and transcytosis via diverse signaling pathways. Abundant in almost every cell type in the lung, including type I epithelial cells, endothelial cells, smooth muscle cells, fibroblasts, macrophages, and neutrophils, cav-1 plays a crucial role in the pathogenesis of acute lung injury (ALI). ALI and its severe form, acute respiratory distress syndrome (ARDS), are responsible for significant morbidity and mortality in intensive care units, despite improvement in ventilation strategies. The pathogenesis of ARDS is still poorly understood, and therapeutic options remain limited. In this article, we summarize recent data regarding the regulation and function of cav-1 in lung biology and pathology, in particular as it relates to ALI. We further discuss the potential molecular and cellular mechanisms by which cav-1 expression contributes to ALI. Investigating the cellular functions of cav-1 may provide new insights for understanding the pathogenesis of ALI and provide novel targets for therapeutic interventions in the future.",,"['Jin, Yang', 'Lee, Seon-Jin', 'Minshall, Richard D.', 'Choi, Augustine M. K.']",,,,
,PMC,"Up-regulation of microRNAs, miR21 and miR23a in human liver cancer cells treated with Coptidis rhizoma aqueous extract",http://dx.doi.org/10.3892/etm.2010.164,PMC3440660,,,"Coptidis rhizoma (CR; Huanglian in Chinese) has been used for the treatment of cancer in Chinese medicine, and recent studies have supported its use in cancer therapy. MicroRNAs (miRNAs) play an important role in the pathophysiology of human cancers. We examined alterations in the miRNA profile of hepatocellular carcinoma (HCC) cells after treatment with Coptidis rhizoma aqueous extract (CRAE). An on-chip microarray method was used to detect alterations in the expression profile of miRNAs in human HCC MHCC97-L cells after exposure to 175 μg/ml CRAE. Altered expression of several miRNAs was detected in the MHCC97-L cells after treatment with 175 μg/ml CRAE. The microarray results were validated by quantitative real-time PCR (qRT-PCR). Consistent results were obtained; qRT-PCR confirmed that both miR-21 and miR-23a were significantly up-regulated. TargetScan and PicTar microRNA databases were used to predict the possible target genes of the altered miRNAs. The results showed that the altered miRNAs after CRAE treatment may serve as markers for the therapy of liver cancer. To the best of our knowledge, this is the first report on the up-regulation of miRNAs, miR21 and miR23a in human liver cancer cells treated with CRAE. Our results suggest that CRAE targets miR-21 and miR-23a in liver cancer cells supporting the potential application of CRAE in the treatment of HCC.",,"['ZHU, MEIFEN', 'WANG, NING', 'TSAO, SAI-WAH', 'YUEN, MAN-FUNG', 'FENG, YIGANG', 'WAN, THOMAS S.K.', 'MAN, KWAN', 'FENG, YIBIN']",,,,
,PMC,The paradox of the neutrophilˈs role in tissue injury,http://dx.doi.org/10.1189/jlb.0910538,PMC6608002,,,"The neutrophil is an essential component of the innate immune system, and its function is vital to human life. Its production increases in response to virtually all forms of inflammation, and subsequently, it can accumulate in blood and tissue to varying degrees. Although its participation in the inflammatory response is often salutary by nature of its normal interaction with vascular endothelium and its capability to enter tissues and respond to chemotactic gradients and to phagocytize and kill microrganisms, it can contribute to processes that impair vascular integrity and blood flow. The mechanisms that the neutrophil uses to kill microorganisms also have the potential to injure normal tissue under special circumstances. Its paradoxical role in the pathophysiology of disease is particularly, but not exclusively, notable in seven circumstances: 1) diabetic retinopathy, 2) sickle cell disease, 3) TRALI, 4) ARDS, 5) renal microvasculopathy, 6) stroke, and 7) acute coronary artery syndrome. The activated neutrophilˈs capability to become adhesive to endothelium, to generate highly ROS, and to secrete proteases gives it the potential to induce local vascular and tissue injury. In this review, we summarize the evidence for its role as a mediator of tissue injury in these seven conditions, making it or its products potential therapeutic targets.",,"['Segel, George B.', 'Halterman, Marc W.', 'Lichtman, Marshall A.']",,,,
,PMC,Single-dose intranasal administration with mDEF201 (adenovirus vectored mouse interferon-alpha) confers protection from mortality in a lethal SARS-CoV BALB/c mouse model,http://dx.doi.org/10.1016/j.antiviral.2010.11.007,PMC3018546,,,"Interferons (IFNs) are a first line of defense against viral infection. Herein we describe the use of an adenovirus vectored mouse IFN alpha gene (mDEF201) as a prophylactic and treatment countermeasure in a SARS-CoV-infected BALB/c mouse model. Complete survival protection was observed in mice given a single dose of mDEF201 administered intranasally 1, 3, 5, 7, or 14 days prior to lethal SARS-CoV challenge (p<0.001), and body weights of these treated mice were unaffected by the challenge. In addition, low doses of mDEF201 protected lungs in a dose dependent manner as measured by a reduction in gross pathology. Intranasal treatment with mDEF201 ranging from 10(6) to 10(8) PFU significantly protected mice against a lethal SARS-CoV infection in a dose dependent manner up to 12 h post infection (P<0.001). The data suggest that mDEF201 is a new class of antiviral agent further development as treatment for SARS-CoV infections.",,"['Kumaki, Yohichi', 'Ennis, Jane', 'Rahbar, Ramtin', 'Turner, Jeffrey D.', 'Wandersee, Miles K.', 'Smith, Aaron J.', 'Bailey, Kevin W.', 'Vest, Zachary G.', 'Madsen, Jason R.', 'Li, Joseph K.-K.', 'Barnard, Dale L.']",,,,
,PMC,Mouse STAT2 Restricts Early Dengue Virus Replication,http://dx.doi.org/10.1016/j.chom.2010.10.007,PMC3310429,,,"Dengue virus encodes several interferon antagonists. Among these the NS5 protein binds STAT2, a necessary component of the type-I interferon signaling pathway, and targets it for degradation. We now demonstrate that the ability of dengue NS5 to associate with and degrade STAT2 is species specific. Thus, NS5 is able to bind and degrade human STAT2 but not mouse STAT2. This difference was exploited to demonstrate, absent manipulation of the viral genome, that NS5 mediated IFN antagonism is essential for efficient virus replication. Moreover, we demonstrate that differences in NS5 mediated binding and degradation between human and mouse STAT2 maps to a region within the STAT2 coiled-coil domain. By using STAT2−/− mice, we also demonstrate that mouse STAT2 restricts early dengue virus replication in vivo. These results suggest that overcoming this restriction through transgenic mouse technology may help in the development of a long-sought immune-competent mouse model of dengue virus infection.",,"['Ashour, Joseph', 'Morrison, Juliet', 'Laurent-Rolle, Maudry', 'Belicha-Villanueva, Alan', 'Plumlee, Courtney Ray', 'Bernal-Rubio, Dabeiba', 'Williams, Kate', 'Harris, Eva', 'Fernandez-Sesma, Ana', 'Schindler, Christian', 'García-Sastre, Adolfo']",,,,
,PMC,Differentiation between Human Coronaviruses NL63 and 229E Using a Novel Double-Antibody Sandwich Enzyme-Linked Immunosorbent Assay Based on Specific Monoclonal Antibodies,http://dx.doi.org/10.1128/CVI.00355-10,PMC3019789,,,"Human coronaviruses (HCoVs) are responsible for respiratory tract infections ranging from common colds to severe acute respiratory syndrome. HCoV-NL63 and HCoV-229E are two of the four HCoVs that circulate worldwide and are close phylogenetic relatives. HCoV infections can lead to hospitalization of children, elderly individuals, and immunocompromised patients. Globally, approximately 5% of all upper and lower respiratory tract infections in hospitalized children are caused by HCoV-229E and HCoV-NL63. The latter virus has recently been associated with the childhood disease croup. Thus, differentiation between the two viruses is relevant for epidemiology studies. The aim of this study was to develop a double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) as a potential tool for identification and differentiation between HCoV-NL63 and HCoV-229E. The nucleocapsid (N) proteins of HCoV-NL63 and HCoV-229E were expressed in an Escherichia coli system and used to immunize mice in order to obtain monoclonal antibodies (MAbs) specific for each virus. Three specific MAbs to HCoV-NL63, one MAb specific to HCoV-229E, and four MAbs that recognized both viruses were obtained. After their characterization, three MAbs were selected in order to develop a differential DAS-ELISA. The described assay could detect up to 3 ng/ml of N protein and 50 50% tissue culture infective doses/ml of virus stock. No cross-reactivity with other human coronaviruses or closely related animal coronaviruses was found. The newly developed DAS-ELISA was species specific, and therefore, it could be considered a potential tool for detection and differentiation of HCoV-NL63 and HCoV-229E infections.",,"['Sastre, Patricia', 'Dijkman, Ronald', 'Camuñas, Ana', 'Ruiz, Tamara', 'Jebbink, Maarten F.', 'van der Hoek, Lia', 'Vela, Carmen', 'Rueda, Paloma']",,,,
,PMC,Human Leukocyte Antigens A*3001 and A*3002 Show Distinct Peptide-Binding Patterns of the Mycobacterium tuberculosis Protein TB10.4: Consequences for Immune Recognition,http://dx.doi.org/10.1128/CVI.00302-10,PMC3019778,,,"High-tuberculosis (TB)-burden countries are located in sub-Saharan Africa. We examined the frequency of human leukocyte antigen (HLA) alleles, followed by recombinant expression of the most frequent HLA-A alleles, i.e., HLA-A*3001 and HLA-A*3002, to study differences in mycobacterial peptide presentation and CD8(+) T-cell recognition. We screened a peptide library (9-mer peptides with an 8-amino-acid overlap) for binding, affinity, and off-rate of the Mycobacterium tuberculosis-associated antigen TB10.4 and identified only three TB10.4 peptides with considerable binding to HLA-A*3001. In contrast, 22 peptides bound to HLA-A*3002. This reflects a marked difference in the binding preference between the two alleles, with A*3002 tolerating a more promiscuous peptide-binding pattern and A*3001 accommodating only a very selective peptide repertoire. Subsequent analysis of the affinity and off-rate of the binding peptides revealed a strong affinity (8 nM to 7 μM) and moderate off-rate (20 min to 3 h) for both alleles. Construction of HLA-A*3001 and HLA-A*3002 tetramers containing selected binding peptides from TB10.4, including a peptide which was shared among both alleles, QIMYNYPAM (TB10.4(3-11)), allowed us to enumerate epitope-specific T cells in HLA-A*3001- and HLA-A*3002-typed patients with active TB. HLA-A*3001 and HLA-A*3002 major histocompatibility complex-peptide complexes were recognized in individuals with active TB, irrespective of their homozygous HLA-A*3001 or HLA-A*3002 genetic background. The antigen-specific T cells exhibited the CD45RA(+) CCR7(+) precursor phenotype and the interleukin-7 receptor (CD127), which were different from the phenotype and receptor exhibited by the parental CD8(+) T-cell population.",,"['Axelsson-Robertson, Rebecca', 'Ahmed, Raija K.', 'Weichold, Frank F.', 'Ehlers, Marthie M.', 'Kock, Marleen M.', 'Sizemore, Donata', 'Sadoff, Jerry', 'Maeurer, Markus']",,,,
,PMC,Development and Characterization of a Highly Specific and Sensitive SYBR Green Reverse Transcriptase PCR Assay for Detection of the 2009 Pandemic H1N1 Influenza Virus on the Basis of Sequence Signatures,http://dx.doi.org/10.1128/JCM.01142-10,PMC3020443,,,"The emergence and rapid spread of the 2009 H1N1 pandemic influenza virus showed that many diagnostic tests were unsuitable for detecting the novel virus isolates. In most countries the probe-based TaqMan assay developed by the U.S. Centers for Disease Control and Prevention was used for diagnostic purposes. The substantial sequence data that became available during the course of the pandemic created the opportunity to utilize bioinformatics tools to evaluate the unique sequence properties of this virus for the development of diagnostic tests. We used a comprehensive computational approach to examine conserved 2009 H1N1 sequence signatures that are at least 20 nucleotides long and contain at least two mismatches compared to any other known H1N1 genome. We found that the hemagglutinin (HA) and neuraminidase (NA) genes contained sequence signatures that are highly conserved among 2009 H1N1 isolates. Based on the NA gene signatures, we used Visual-OMP to design primers with optimal hybridization affinity and we used ThermoBLAST to minimize amplification artifacts. This procedure resulted in a highly sensitive and discriminatory 2009 H1N1 detection assay. Importantly, we found that the primer set can be used reliably in both a conventional TaqMan and a SYBR green reverse transcriptase (RT)-PCR assay with no loss of specificity or sensitivity. We validated the diagnostic accuracy of the NA SYBR green assay with 125 clinical specimens obtained between May and August 2009 in Chile, and we showed diagnostic efficacy comparable to the CDC assay. Our approach highlights the use of systematic computational approaches to develop robust diagnostic tests during a viral pandemic.",,"['Medina, Rafael A.', 'Rojas, Mark', 'Tuin, Astrid', 'Huff, Stephen', 'Ferres, Marcela', 'Martinez-Valdebenito, Constanza', 'Godoy, Paula', 'García-Sastre, Adolfo', 'Fofanov, Yuriy', 'SantaLucia, John']",,,,
,PMC,Parameterizing state–space models for infectious disease dynamics by generalized profiling: measles in Ontario,http://dx.doi.org/10.1098/rsif.2010.0412,PMC3104327,,,"Parameter estimation for infectious disease models is important for basic understanding (e.g. to identify major transmission pathways), for forecasting emerging epidemics, and for designing control measures. Differential equation models are often used, but statistical inference for differential equations suffers from numerical challenges and poor agreement between observational data and deterministic models. Accounting for these departures via stochastic model terms requires full specification of the probabilistic dynamics, and computationally demanding estimation methods. Here, we demonstrate the utility of an alternative approach, generalized profiling, which provides robustness to violations of a deterministic model without needing to specify a complete probabilistic model. We introduce novel means for estimating the robustness parameters and for statistical inference in this framework. The methods are applied to a model for pre-vaccination measles incidence in Ontario, and we demonstrate the statistical validity of our inference through extensive simulation. The results confirm that school term versus summer drives seasonality of transmission, but we find no effects of short school breaks and the estimated basic reproductive ratio ℛ(0) greatly exceeds previous estimates. The approach applies naturally to any system for which candidate differential equations are available, and avoids many challenges that have limited Monte Carlo inference for state–space models.",,"['Hooker, Giles', 'Ellner, Stephen P.', 'Roditi, Laura De Vargas', 'Earn, David J. D.']",,,,
,PMC,Pandemic Swine-Origin H1N1 Influenza A Virus Isolates Show Heterogeneous Virulence in Macaques,http://dx.doi.org/10.1128/JVI.01848-10,PMC3020514,,,"The first influenza pandemic of the new millennium was caused by a newly emerged swine-origin influenza virus (SOIV) (H1N1). This new virus is characterized by a previously unknown constellation of gene segments derived from North American and Eurasian swine lineages and the absence of common markers predictive of human adaptation. Overall, human infections appeared to be mild, but an alarming number of young individuals presented with symptoms atypical for seasonal influenza. The new SOIV also showed a sustained human-to-human transmissibility and higher reproduction ratio than common seasonal viruses, altogether indicating a higher pathogenic potential for this newly emerged virus. To study the virulence of the SOIV, we used a recently established cynomolgus macaque model and compared parameters of clinical disease, virology, host responses, and pathology/histopathology with a current seasonal H1N1 virus. We here show that infection of macaques with two genetically similar but clinically distinct SOIV isolates from the early stage of the pandemic (A/Mexico/4108/2009 and A/Mexico/InDRE4487/2009) resulted in upper and lower respiratory tract infections and clinical disease ranging from mild to severe pneumonia that was clearly advanced over the mild infection caused by A/Kawasaki/UTK-4/2009, a current seasonal strain. Unexpectedly, we observed heterogeneity among the two SOIV isolates in virus replication, host transcriptional and cytokine responses, and disease progression, demonstrating a higher pathogenic potential for A/Mexico/InDRE4487/2009. Differences in virulence may explain more severe disease, as was seen with certain individuals infected with the emerged pandemic influenza virus. Thus, the nonhuman primate model closely mimics influenza in humans.",,"['Safronetz, David', 'Rockx, Barry', 'Feldmann, Friederike', 'Belisle, Sarah E.', 'Palermo, Robert E.', 'Brining, Douglas', 'Gardner, Don', 'Proll, Sean C.', 'Marzi, Andrea', 'Tsuda, Yoshimi', 'LaCasse, Rachel A.', 'Kercher, Lisa', 'York, Anthony', 'Korth, Marcus J.', 'Long, Dan', 'Rosenke, Rebecca', 'Shupert, W. Lesley', 'Aranda, Celia Alpuche', 'Mattoon, John S.', 'Kobasa, Darwyn', 'Kobinger, Gary', 'Li, Yan', 'Taubenberger, Jeffery K.', 'Richt, Jürgen A.', 'Parnell, Michael', 'Ebihara, Hideki', 'Kawaoka, Yoshihiro', 'Katze, Michael G.', 'Feldmann, Heinz']",,,,
,PMC,Mapping the Landscape of Host-Pathogen Coevolution: HLA Class I Binding and Its Relationship with Evolutionary Conservation in Human and Viral Proteins,http://dx.doi.org/10.1128/JVI.01966-10,PMC3020499,,,"The high diversity of HLA binding preferences has been driven by the sequence diversity of short segments of relevant pathogenic proteins presented by HLA molecules to the immune system. To identify possible commonalities in HLA binding preferences, we quantify these using a novel measure termed “targeting efficiency,” which captures the correlation between HLA-peptide binding affinities and the conservation of the targeted proteomic regions. Analysis of targeting efficiencies for 95 HLA class I alleles over thousands of human proteins and 52 human viruses indicates that HLA molecules preferentially target conserved regions in these proteomes, although the arboviral Flaviviridae are a notable exception where nonconserved regions are preferentially targeted by most alleles. HLA-A alleles and several HLA-B alleles that have maintained close sequence identity with chimpanzee homologues target conserved human proteins and DNA viruses such as Herpesviridae and Adenoviridae most efficiently, while all HLA-B alleles studied efficiently target RNA viruses. These patterns of host and pathogen specialization are both consistent with coevolutionary selection and functionally relevant in specific cases; for example, preferential HLA targeting of conserved proteomic regions is associated with improved outcomes in HIV infection and with protection against dengue hemorrhagic fever. Efficiency analysis provides a novel perspective on the coevolutionary relationship between HLA class I molecular diversity, self-derived peptides that shape T-cell immunity through ontogeny, and the broad range of viruses that subsequently engage with the adaptive immune response.",,"['Hertz, Tomer', 'Nolan, David', 'James, Ian', 'John, Mina', 'Gaudieri, Silvana', 'Phillips, Elizabeth', 'Huang, Jim C.', 'Riadi, Gonzalo', 'Mallal, Simon', 'Jojic, Nebojsa']",,,,
,PMC,Modeling of the Toll-like receptor 3 and a putative Toll-like receptor 3 antagonist encoded by the African swine fever virus,http://dx.doi.org/10.1002/pro.554,PMC3048410,,,"African swine fever virus (ASFV) is a large double-stranded DNA virus responsible for a lethal pig disease, to which no vaccine has ever been obtained. Its genome encodes a number of proteins involved in virus survival and transmission in its hosts, in particular proteins that inhibit signaling pathways in infected macrophages and, thus, interfere with the host's innate immune response. A recently identified novel ASFV viral protein (pI329L) was found to inhibit the Toll-like receptor 3 (TLR3) signaling pathway, TLR3 being a crucial “danger detector.” pI329L has been predicted to be a transmembrane protein containing extracellular putative leucine-rich repeats similar to TLR3, suggesting that pI329L might act as a TLR3 decoy. To explore this idea, we used comparative modeling and other structure prediction protocols to propose (a) a model for the TLR3–Toll-interleukin-1 receptor homodimer and (b) a structural fold for pI329L, detailed at atomistic level for its cytoplasmic domain. As this later domain shares only remote sequence relationships with the available TLR3 templates, a more complex modeling strategy was employed that combines the iterative implementation of (multi)threading/assembly/refinement (I-TASSER) structural prediction with expertise-guided posterior refinement. The final pI329L model presents a plausible fold, good structural quality, is consistent with the available experimental data, and it corroborates our hypothesis of pI329L being a TLR3 antagonist.",,"['Henriques, Elsa S', 'Brito, Rui M M', 'Soares, Hugo', 'Ventura, Sónia', 'de Oliveira, Vivian L', 'Parkhouse, R Michael E']",,,,
,PMC,Transcriptional Mechanisms Regulating Ca(2+) Homeostasis,http://dx.doi.org/10.1016/j.ceca.2010.10.001,PMC3225030,,,"Ca(2+) is a dynamic cellular secondary messenger which mediates a vast array of cellular responses. Control over these processes is achieved via an extensive combination of pumps and channels which regulate the concentration of Ca(2+) within not only the cytosol but also all intracellular compartments. Precisely how these pumps and channels are regulated is only partially understood, however, recent investigations have identified members of the Early Growth Response (EGR) family of zinc finger transcription factors as critical players in this process. The roles of several other transcription factors in control of Ca(2+) homeostasis have also been demonstrated, including Wilms Tumor Suppressor 1 (WT1), Nuclear Factor of Activated T cells (NFAT) and c-myc. In this review, we will discuss not only how these transcription factors regulate the expression of the major proteins involved in control of Ca(2+) homeostasis, but also how this transcriptional remodeling of Ca(2+) homeostasis affects Ca(2+) dynamics and cellular responses.",,"['Ritchie, Michael F.', 'Zhou, Yandong', 'Soboloff, Jonathan']",,,,
,PMC,Murine coronavirus neuropathogenesis: determinants of virulence,http://dx.doi.org/10.3109/13550284.2010.529238,PMC3153983,,,"Murine coronavirus, mouse hepatitis virus (MHV), causes various diseases depending on the strain and route of inoculation. Both the JHM and A59 strains, when inoculated intracranially or intranasally, are neurovirulent. Comparison of the highly virulent JHM isolate, JHM.SD, with less virulent JHM isolates and with A59 has been used to determine the mechanisms and genes responsible for high neuropathogenicity of MHV. The focus of this review is on the contributions of viral spread, replication and innate and adaptive immunity to MHV neuropathogenesis. JHM.SD spreads more quickly among neurons than less neurovirulent MHVs, and is able to spread in the absence of the canonical MHV receptor, CEACAM1a. The observation that JHM.SD infects more cells and expresses more antigen, but produces less infectious virus per cell than A59 implies that efficient replication is not always a correlate of high neurovirulence. This is likely due to the unstable nature of the JHM.SD spike protein (S). JHM.SD induces a generally protective innate immune response; however, the strong neutrophil response may be more pathogenic than protective. In addition JHM.SD induces only a minimal T cell response, while the strong T cell response and the concomitant IFNγ induced by the less neurovirulent A59 is protective. Differences in the S and nucleocapsid (N) proteins between A59 and JHM.SD contribute to JHM.SD neuropathogenicity. The hemmagglutinin-esterase (HE) protein may enhance neuropathogenicity of some MHV isolates, but is unlikely a major contributor to the high neuroviruence of JHM.SD. Further data suggests that neither the internal (I) protein, nor nonstructural proteins ns4, and ns2 are significant contributors to neurovirulence.",,"['Cowley, Timothy J.', 'Weiss, Susan R.']",,,,
,PMC,"Contact intervals, survival analysis of epidemic data, and estimation of R(0)",http://dx.doi.org/10.1093/biostatistics/kxq068,PMC3114649,,,"We argue that the time from the onset of infectiousness to infectious contact, which we call the “contact interval,” is a better basis for inference in epidemic data than the generation or serial interval. Since contact intervals can be right censored, survival analysis is the natural approach to estimation. Estimates of the contact interval distribution can be used to estimate R(0) in both mass-action and network-based models. We apply these methods to 2 data sets from the 2009 influenza A(H1N1) pandemic.",,"Kenah, Eben",,,,
,PMC,Protection of human erythrocyte using Crinumasiaticum extract and lycorine from oxidative damage induced by 2-amidinopropane,http://dx.doi.org/10.1016/j.sjbs.2010.11.001,PMC3730559,,,"The intention of this investigation was to evaluate the free radical scavenging activity and erythrocyte protective activity of ethanolic extract of Crinumasiaticum (L) and lycorine. The ethanolic extract of C. asiaticum (L) and lycorine were found to have different levels of antioxidant properties in the test models. Both ethanolic extract of C. asiaticum (L) (0.5–2.5 mg/ml) and lycorine (0.010 mg–0.050 mg/ml) increases the percentage of lipid peroxidation inhibition (26.25 ± 0.23% and 19.25 ± 0.23%) and enhances the free radical scavenging activity (20.92 ± 0.22% and 20.52 ± 0.22%), scavenging of hydrogen peroxide (25.67 ± 0.17% and 23.07 ± 0.3%) superoxide anion scavenging activity (27.69 ± 0.16% and 16.09 ± 0.7%) at concentration of 2.5 and 0.050 mg of C. asiaticum (L) and lycorine, respectively. But compared with tocopherol (P < 0.05) less activity was observed by C. asiaticum (L) and lycorine. The ethanolic extract of C. asiaticum (L) and lycorine were normalized to reduce the level of glutathione and also to sustain the status of protein in erythrocytes during the peroxyl radical [2,2-azobis (2-amidinopropane) dihydrochloride (AAPH)] induced oxidative damage in ex vivo model. The present results of the investigations demonstrated that protective nature of the C. asiaticum (L) and lycorine will be considered as a significant natural antioxidant source.",,"['Ilavenil, S.', 'Kaleeswaran, B.', 'Sumitha, P.', 'Tamilvendan, D.', 'Ravikumar, S.']",,,,
,PMC,Identification of Phase-I Metabolites of the Kv1.3 Blocker PAP-1 (5-(4-Phenoxybutoxy)psoralen) in the Rat,http://dx.doi.org/10.3109/00498254.2010.532886,PMC3644211,,,"PAP-1 (5-(4-phenoxybutoxy)psoralen), a potent small-molecule blocker of the voltage-gated potassium Kv1.3 channel, is currently in pre-clinical development for psoriasis. The present study was undertaken to identify the major phase-I metabolites of PAP-1 in rats. Following oral administration at 50 mg/kg, bile, plasma, urine and feces were collected, and separated by reversed-phase HPLC after sample preparation by solid-phase extraction. Five phase-I metabolites, i.e., 5-(oxybutyric-acid)psoralen (M1), 5-[4-(4-hydroxybutoxy)]psoralen (M2), 5-[4-(4-hydroxyphenoxy)]psoralen (M3), 5-[4-(3-hydroxyphenoxy)]psoralen (M4), 8-hydroxyl-5-(4-phenoxybutoxy)psoralen (M5), were isolated and identified by mass spectrometry and NMR spectroscopy. M3, M4 and M5 were hydroxylated products, while M1 and M2 were O-dealkylation products. Incubation of PAP-1 with rat liver microsomes rendered the same five major metabolites in a NADPH-dependent manner suggesting that cytochrome P450 (CYP) enzymes are involved in PAP-1 metabolism. Inhibitors of rat CYP1A1/2 (alpha-naphthoflavone) and CYP3A (ketoconazole) but not CYP2D6, CYP2E or CYP2C9 blocked the metabolism of PAP-1 in rat microsomes. Of the five metabolites M3, M4 and M5 were found to inhibit Kv1.3 currents with nanomolar IC(50)s, while M1 and M2 were inactive. Our results identified the Kv1.3-inactive M1 as the major phase-I metabolite, and suggest that hydroxylation and O-dealkylation are the major pathways of PAP-1 metabolism principally via CYP1A1/2 and CYP3A. We further conducted a 6-months repeat-dose toxicity study with PAP-1 at 50 mg/kg in both male and female rats and did not observe any changes in hematology, blood chemistry, body weight, histology of any major organ, or speeding up of metabolism suggesting induction of its metabolizing enzymes (presumably CYPs).",,"['Hao, Bin', 'Chen, Zhong-Wei', 'Zhou, Xiang-Jun', 'Zimin, Pavel I.', 'Miljanich, George P.', 'Wulff, Heike', 'Wang, Yong-Xiang']",,,,
,PMC,Role of two-way airflow owing to temperature difference in severe acute respiratory syndrome transmission: revisiting the largest nosocomial severe acute respiratory syndrome outbreak in Hong Kong,http://dx.doi.org/10.1098/rsif.2010.0486,PMC3061095,,,"By revisiting the air distribution and bioaerosol dispersion in Ward 8A where the largest nosocomial severe acute respiratory syndrome (SARS) outbreak occurred in Hong Kong in 2003, we found an interesting phenomenon. Although all the cubicles were in ‘positive pressure’ towards the corridor, the virus-containing bioaerosols generated from the index patient's cubicle were still transmitted to other cubicles, which cannot be explained in a traditional manner. A multi-zone model combining the two-way airflow effect was used to analyse this phenomenon. The multi-zone airflow model was evaluated by our experimental data. Comparing with the previous computational fluid dynamic simulation results, we found that the air exchange owing to the small temperature differences between cubicles played a major role in SARS transmission. Additionally, the validated multi-zone model combining the two-way airflow effect could simulate the pollutant transport with reasonable accuracy but much less computational time. A probable improvement in general ward design was also proposed.",,"['Chen, Chun', 'Zhao, Bin', 'Yang, Xudong', 'Li, Yuguo']",,,,
,PMC,Characterization of Bafinivirus Main Protease Autoprocessing Activities,http://dx.doi.org/10.1128/JVI.01716-10,PMC3020504,,,"The production of functional nidovirus replication-transcription complexes involves extensive proteolytic processing by virus-encoded proteases. In this study, we characterized the viral main protease (M(pro)) of the type species, White bream virus (WBV), of the newly established genus Bafinivirus (order Nidovirales, family Coronaviridae, subfamily Torovirinae). Comparative sequence analysis and mutagenesis data confirmed that the WBV M(pro) is a picornavirus 3C-like serine protease that uses a Ser-His-Asp catalytic triad embedded in a predicted two-β-barrel fold, which is extended by a third domain at its C terminus. Bacterially expressed WBV M(pro) autocatalytically released itself from flanking sequences and was able to mediate proteolytic processing in trans. Using N-terminal sequencing of autoproteolytic processing products we tentatively identified Gln↓(Ala, Thr) as a substrate consensus sequence. Mutagenesis data provided evidence to suggest that two conserved His and Thr residues are part of the S1 subsite of the enzyme's substrate-binding pocket. Interestingly, we observed two N-proximal and two C-proximal autoprocessing sites in the bacterial expression system. The detection of two major forms of M(pro), resulting from processing at two different N-proximal and one C-proximal site, in WBV-infected epithelioma papulosum cyprini cells confirmed the biological relevance of the biochemical data obtained in heterologous expression systems. To our knowledge, the use of alternative M(pro) autoprocessing sites has not been described previously for other nidovirus M(pro) domains. The data presented in this study lend further support to our previous conclusion that bafiniviruses represent a distinct group of viruses that significantly diverged from other phylogenetic clusters of the order Nidovirales.",,"['Ulferts, Rachel', 'Mettenleiter, Thomas C.', 'Ziebuhr, John']",,,,
,PMC,"The Receptor-Binding Domain of Influenza Virus Hemagglutinin Produced in Escherichia coli Folds into Its Native, Immunogenic Structure",http://dx.doi.org/10.1128/JVI.01412-10,PMC3020035,,,"The hemagglutinin (HA) surface glycoprotein promotes influenza virus entry and is the key protective antigen in natural immunity and vaccines. The HA protein is a trimeric envelope glycoprotein consisting of a globular receptor-binding domain (HA-RBD) that is inserted into a membrane fusion-mediating stalk domain. Similar to other class I viral fusion proteins, the fusogenic stalk domain spontaneously refolds into its postfusion conformation when expressed in isolation, consistent with this domain being trapped in a metastable conformation. Using X-ray crystallography, we show that the influenza virus HA-RBD refolds spontaneously into its native, immunogenic structure even when expressed in an unglycosylated form in Escherichia coli. In the 2.10-Å structure of the HA-RBD, the receptor-binding pocket is intact and its conformational epitopes are preserved. Recombinant HA-RBD is immunogenic and protective in ferrets, and the protein also binds with specificity to sera from influenza virus-infected humans. Overall, the data provide a structural basis for the rapid production of influenza vaccines in E. coli. From an evolutionary standpoint, the ability of the HA-RBD to refold spontaneously into its native conformation suggests that influenza virus acquired this domain as an insertion into an ancestral membrane-fusion domain. The insertion of independently folding domains into fusogenic stalk domains may be a common feature of class I viral fusion proteins.",,"['DuBois, Rebecca M.', 'Aguilar-Yañez, José Manuel', 'Mendoza-Ochoa, Gonzalo I.', 'Oropeza-Almazán, Yuriana', 'Schultz-Cherry, Stacey', 'Alvarez, Mario Moisés', 'White, Stephen W.', 'Russell, Charles J.']",,,,
,PMC,A Transmembrane Serine Protease Is Linked to the Severe Acute Respiratory Syndrome Coronavirus Receptor and Activates Virus Entry,http://dx.doi.org/10.1128/JVI.02062-10,PMC3020023,,,"Spike (S) proteins, the defining projections of the enveloped coronaviruses (CoVs), mediate cell entry by connecting viruses to plasma membrane receptors and by catalyzing subsequent virus-cell membrane fusions. The latter membrane fusion requires an S protein conformational flexibility that is facilitated by proteolytic cleavages. We hypothesized that the most relevant cellular proteases in this process are those closely linked to host cell receptors. The primary receptor for the human severe acute respiratory syndrome CoV (SARS) CoV is angiotensin-converting enzyme 2 (ACE2). ACE2 immunoprecipitation captured transmembrane protease/serine subfamily member 2 (TMPRSS2), a known human airway and alveolar protease. ACE2 and TMPRSS2 colocalized on cell surfaces and enhanced the cell entry of both SARS S-pseudotyped HIV and authentic SARS-CoV. Enhanced entry correlated with TMPRSS2-mediated proteolysis of both S and ACE2. These findings indicate that a cell surface complex comprising a primary receptor and a separate endoprotease operates as a portal for activation of SARS-CoV cell entry.",,"['Shulla, Ana', 'Heald-Sargent, Taylor', 'Subramanya, Gitanjali', 'Zhao, Jincun', 'Perlman, Stanley', 'Gallagher, Tom']",,,,
,PMC,Structural Studies of Hantaan Virus,http://dx.doi.org/10.1128/JVI.01847-10,PMC3020021,,,"Hantaan virus is the prototypic member of the Hantavirus genus within the family Bunyaviridae and is a causative agent of the potentially fatal hemorrhagic fever with renal syndrome. The Bunyaviridae are a family of negative-sense RNA viruses with three-part segmented genomes. Virions are enveloped and decorated with spikes derived from a pair of glycoproteins (Gn and Gc). Here, we present cryo-electron tomography and single-particle cryo-electron microscopy studies of Hantaan virus virions. We have determined the structure of the tetrameric Gn-Gc spike complex to a resolution of 2.5 nm and show that spikes are ordered in lattices on the virion surface. Large cytoplasmic extensions associated with each Gn-Gc spike also form a lattice on the inner surface of the viral membrane. Rod-shaped ribonucleoprotein complexes are arranged into nearly parallel pairs and triplets within virions. Our results differ from the T=12 icosahedral organization found for some bunyaviruses. However, a comparison of our results with the previous tomographic studies of the nonpathogenic Tula hantavirus indicates a common structural organization for hantaviruses.",,"['Battisti, Anthony J.', 'Chu, Yong-Kyu', 'Chipman, Paul R.', 'Kaufmann, Bärbel', 'Jonsson, Colleen B.', 'Rossmann, Michael G.']",,,,
,PMC,Genomic Analysis Reveals Pre- and Postchallenge Differences in a Rhesus Macaque AIDS Vaccine Trial: Insights into Mechanisms of Vaccine Efficacy,http://dx.doi.org/10.1128/JVI.01522-10,PMC3020003,,,"We have employed global transcriptional profiling of whole blood to identify biologically relevant changes in cellular gene expression in response to alternative AIDS vaccine strategies with subsequent viral challenge in a rhesus macaque vaccine model. Samples were taken at day 0 (prechallenge), day 14 (peak viremia), and week 12 (set point) from animals immunized with replicating adenovirus type 5 host range (Ad5hr) recombinant viruses expressing human immunodeficiency virus HIV(env)(89.6P), simian immunodeficiency virus SIV(gag)(239), or SIV(nef)(239) alone or in combination with two intramuscular boosts with HIV(89.6P)gp140ΔCFI protein (L. J. Patterson et al., Virology 374:322-337, 2008), and each treatment resulted in significant control of viremia following simian-human immunodeficiency virus SHIV(89.6P) challenge (six animals per group plus six controls). At day 0, 8 weeks after the last treatment, the microarray profiles revealed significant prechallenge differences between treatment groups; data from the best-protected animals led to identification of a network of genes related to B cell development and lymphocyte survival. At peak viremia, expression profiles of the immunized groups were extremely similar, and comparisons to control animals reflected immunological differences other than effector T cell functions. Suggested protective mechanisms for vaccinated animals included upregulation of interleukin-27, a cytokine known to inhibit lentivirus replication, and increased expression of complement components, which may synergize with vaccine-induced antibodies. Divergent expression profiles at set point for the immunized groups implied distinct immunological responses despite phenotypic similarities in viral load and CD4(+) T cell levels. Data for the gp140-boosted group provided evidence for antibody-dependent, cell-mediated viral control, whereas animals immunized with only the replicating Ad5hr recombinants exhibited a different evolution of the B cell compartment even at 3 months postchallenge. This study demonstrates the sensitivity and discrimination of gene expression profiling of whole blood as an analytical tool in AIDS vaccine trials, providing unique insights into in vivo mechanisms and potential correlates of protection.",,"['Palermo, Robert E.', 'Patterson, L. Jean', 'Aicher, Lauri D.', 'Korth, Marcus J.', 'Robert-Guroff, Marjorie', 'Katze, Michael G.']",,,,
,PMC,Interaction of Hsp40 with influenza virus M2 protein: implications for PKR signaling pathway,http://dx.doi.org/10.1007/s13238-010-0115-x,PMC4875119,,,"Influenza virus contains three integral membrane proteins: haemagglutinin, neuraminidase, and matrix protein (M1 and M2). Among them, M2 protein functions as an ion channel, important for virus uncoating in endosomes of virus-infected cells and essential for virus replication. In an effort to explore potential new functions of M2 in the virus life cycle, we used yeast two-hybrid system to search for M2-associated cellular proteins. One of the positive clones was identified as human Hsp40/Hdj1, a DnaJ/Hsp40 family protein. Here, we report that both BM2 (M2 of influenza B virus) and A/M2 (M2 of influenza A virus) interacted with Hsp40 in vitro and in vivo. The region of M2-Hsp40 interaction has been mapped to the CTD1 domain of Hsp40. Hsp40 has been reported to be a regulator of PKR signaling pathway by interacting with p58(IPK) that is a cellular inhibitor of PKR. PKR is a crucial component of the host defense response against virus infection. We therefore attempted to understand the relationship among M2, Hsp40 and p58(IPK) by further experimentation. The results demonstrated that both A/M2 and BM2 are able to bind to p58(IPK)in vitro and in vivo and enhance PKR autophosphorylation probably via forming a stable complex with Hsp40 and P58(IPK), and consequently induce cell death. These results suggest that influenza virus M2 protein is involved in p58(IPK) mediated PKR regulation during influenza virus infection, therefore affecting infected-cell life cycle and virus replication.",,"['Guan, Zhenhong', 'Liu, Di', 'Mi, Shuofu', 'Zhang, Jie', 'Ye, Qinong', 'Wang, Ming', 'Gao, George F.', 'Yan, Jinghua']",,,,
,PMC,Selection of reliable reference genes for gene expression study in nasopharyngeal carcinoma,http://dx.doi.org/10.1038/aps.2010.115,PMC4003330,,,"AIM: To construct a system for selecting reference genes (RGs) and to select the most optimal RGs for gene expression studies in nasopharyngeal carcinoma (NPC). METHODS: The total RNAs from 20 NPC samples were each labeled with Cy5-dUTP. To create a common control, the total RNA from 15 nasopharyngeal phlogistic (NP) tissues was mixed and labeled via reverse transcription with Cy3-dUTP. cDNA microarrays containing 14 112 genes were then performed. A mathematical approach was constructed to screen stably expressed genes from the microarray data. Using this method, three genes (YARS, EIF3S7, and PFDN1) were selected as candidate RGs. Furthermore, 7 commonly used RGs (HPRT1, GAPDH, TBP, ACTB, B2M, G6PDH, and HBB) were selected as additional potential RGs. Real-time PCR was used to detect these 10 candidate genes' expression levels and the geNorm program was used to find the optimal RGs for NPC studies. RESULTS: On the basis of the 10 candidate genes' expression stability level, geNorm analysis identified the optimal single RG (YARS or HPRT1) and the most suitable set of RGs (HPRT1, YARS, and EIF3S7) for NPC gene expression studies. In addition, this analysis determined that B2M, G6PDH, and HBB were not appropriate for use as RGs. Interestingly, ACTB was the least stable RG in our study, even though previous studies had indicated that it was one of the most stable RGs. Three novel candidate genes (YARS, EIF3S7, and PFDN1), which were selected from microarray data, were all identified as suitable RGs for NPC research. A RG-selecting system was then constructed, which combines microarray data analysis, a literature screen, real-time PCR, and bioinformatic analysis. CONCLUSION: We construct a RG-selecting system that helps find the optimal RGs. This process, applied to NPC research, determined the single RG (YARS or HPRT1) and the set of RGs (HPRT1, YARS, and EIF3S7) that are the most suitable internal controls.",,"['Guo, Yi', 'Chen, Jia-xin', 'Yang, Shu', 'Fu, Xu-ping', 'Zhang, Zheng', 'Chen, Ke-he', 'Huang, Yan', 'Li, Yao', 'Xie, Yi', 'Mao, Yu-min']",,,,
,PMC,Outpatient Upper Respiratory Tract Viral Infections in Children with Malaria Symptoms in Western Kenya,http://dx.doi.org/10.4269/ajtmh.2010.10-0174,PMC2963960,,,"A cross-sectional study was performed in children 5 through 10 years of age presenting to outpatient clinics in Nyanza Province, Kenya, in which nasal swab and blood specimens were collected during the high malaria transmission season. Patients presenting with malaria-like symptoms within 4 days of fever onset were enrolled in the study. Plasmodium parasitemia was determined by blood smear microscopy. Nasal swabs were screened for a panel of respiratory viruses by polymerase chain reaction. Influenza A, rhinoviruses, and other respiratory viruses were detected in 18%, 26%, and 12% of 197 specimens, respectively. Four of 36 patients with influenza A had a positive malaria blood slide, compared with 20 of 52 patients with rhinovirus. A significant burden of disease caused by influenza A in febrile children during the study period was observed, highlighting the need for further research into the burden of influenza disease in regions where malaria is holoendemic.",,"['Waitumbi, John N.', 'Kuypers, Jane', 'Anyona, Samuel B.', 'Koros, Joseph N.', 'Polhemus, Mark E.', 'Gerlach, Jay', 'Steele, Matthew', 'Englund, Janet A.', 'Neuzil, Kathleen M.', 'Domingo, Gonzalo J.']",,,,
,PMC,C-type lectins do not act as functional receptors for filovirus entry into cells,http://dx.doi.org/10.1016/j.bbrc.2010.10.136,PMC3393133,,,"Cellular C-type lectins have been reported to facilitate filovirus infection by binding to glycans on filovirus glycoprotein (GP). However, it is not clearly known whether interaction between C-type lectins and GP mediates all the steps of virus entry (i.e., attachment, internalization, and membrane fusion). In this study, we generated vesicular stomatitis viruses pseudotyped with mutant GPs that have impaired structures of the putative receptor binding regions and thus reduced ability to infect the monkey kidney cells that are routinely used for virus propagation. We found that infectivities of viruses with the mutant GPs dropped in C-type lectin-expressing cells, parallel with those in the monkey kidney cells, whereas binding activities of these GPs to the C-type lectins were not correlated with the reduced infectivities. These results suggest that C-type lectin-mediated entry of filoviruses requires other cellular molecule(s) that may be involved in virion internalization or membrane fusion.",,"['Matsuno, Keita', 'Nakayama, Eri', 'Noyori, Osamu', 'Marzi, Andrea', 'Ebihara, Hideki', 'Irimura, Tatsuro', 'Feldmann, Heinz', 'Takada, Ayato']",,,,
,PMC,Age-Stratified Bayesian Analysis To Estimate Sensitivity and Specificity of Four Diagnostic Tests for Detection of Cryptosporidium Oocysts in Neonatal Calves,http://dx.doi.org/10.1128/JCM.01424-10,PMC3020464,,,"There is no gold standard diagnostic test for the detection of bovine cryptosporidiosis. Infection is usually highest in 2-week-old calves, and these calves also excrete high numbers of oocysts. These factors may give rise to variations in the sensitivity and specificity of the various diagnostic tests used to detect infection in calves of various ages. An age-stratified Bayesian analysis was carried out to determine the optimum diagnostic test to identify asymptomatic and clinical Cryptosporidium sp. infection in neonatal calves. Fecal samples collected from 82 calves at 1 week, 2 weeks, 3 weeks, and 4 weeks of age were subjected to the following tests: microscopic examination of smears stained with either phenol-auramine O or fluorescein isothiocyanate (FITC)-conjugated anti-Cryptosporidium monoclonal antibody, nested-PCR, and quantitative real-time PCR. The results confirmed a high prevalence of Cryptosporidium sp. infection, as well as a high level of oocyst excretion, in 2-week-old calves. The sensitivities of all the tests varied with the age of the calves. Quantitative real-time PCR proved to be the most sensitive and specific test for detecting infection irrespective of the age of the calf. The microscopic techniques were the least sensitive and exhibited only moderate efficiency with 2-week-old calves excreting large numbers of oocysts, the majority of which were diarrheic. It was concluded that, when interpreting the results of routine tests for bovine cryptosporidiosis, cognizance should be taken of the sensitivity of the tests in relation to the age of the calves and stage of infection.",,"['De Waele, Valerie', 'Berzano, Marco', 'Berkvens, Dirk', 'Speybroeck, Niko', 'Lowery, Colm', 'Mulcahy, Grace M.', 'Murphy, Thomas M.']",,,,
,PMC,The Hydrophobic Domain of Infectious Bronchitis Virus E Protein Alters the Host Secretory Pathway and Is Important for Release of Infectious Virus,http://dx.doi.org/10.1128/JVI.01570-10,PMC3020032,,,"The coronavirus (CoV) E protein plays an important role in virus assembly. The E protein is made in excess during infection and has been shown to have ion channel activity in planar lipid bilayers. However, a role in infection for the unincorporated E or its ion channel activity has not been described. To further investigate the function of the infectious bronchitis virus (IBV) E protein, we developed a recombinant version of IBV in which the E protein was replaced by a mutant containing a heterologous hydrophobic domain. The mutant virus, IBV-EG3, was defective in release of infectious virus particles. Further characterization of IBV-EG3 revealed that damaged particles appeared to accumulate intracellularly. The phenotype of IBV-EG3 suggested that the hydrophobic domain of IBV E may be important for the forward trafficking of cargo, so we determined whether IBV E facilitated the delivery of cargo to the plasma membrane. Surprisingly, we found that IBV E, but not EG3, dramatically reduced the delivery of cargo to the plasma membrane by impeding movement through the Golgi complex. Furthermore, we observed that overexpression of IBV E, but not EG3, induced the disassembly of the Golgi complex. Finally, we determined that the delivery of IBV S to the plasma membrane was reduced in cells infected with wild-type-IBV compared to those infected with IBV-EG3. Our results indicated that the hydrophobic domain of IBV E alters the host secretory pathway to the apparent advantage of the virus.",,"['Ruch, Travis R.', 'Machamer, Carolyn E.']",,,,
,PMC,Modification of Nonstructural Protein 1 of Influenza A Virus by SUMO1,http://dx.doi.org/10.1128/JVI.00877-10,PMC3020006,,,"Nonstructural protein 1 (NS1) is one of the major factors resulting in the efficient infection rate and high level of virulence of influenza A virus. Although consisting of only approximately 230 amino acids, NS1 has the ability to interfere with several systems of the host viral defense. In the present study, we demonstrate that NS1 of the highly pathogenic avian influenza A/Duck/Hubei/L-1/2004 (H5N1) virus interacts with human Ubc9, which is the E2 conjugating enzyme for sumoylation, and we show that SUMO1 is conjugated to H5N1 NS1 in both transfected and infected cells. Furthermore, two lysine residues in the C terminus of NS1 were identified as SUMO1 acceptor sites. When the SUMO1 acceptor sites were removed by mutation, NS1 underwent rapid degradation. Studies of different influenza A virus strains of human and avian origin showed that the majority of viruses possess an NS1 protein that is modified by SUMO1, except for the recently emerged swine-origin influenza A virus (S-OIV) (H1N1). Interestingly, growth of a sumoylation-deficient WSN virus mutant was retarded compared to that of wild-type virus. Together, these results indicate that sumoylation enhances NS1 stability and thus promotes rapid growth of influenza A virus.",,"['Xu, Ke', 'Klenk, Christoph', 'Liu, Bin', 'Keiner, Bjoern', 'Cheng, Jinke', 'Zheng, Bo-Jian', 'Li, Li', 'Han, Qinglin', 'Wang, Chen', 'Li, Tianxian', 'Chen, Ze', 'Shu, Yuelong', 'Liu, Jinhua', 'Klenk, Hans-Dieter', 'Sun, Bing']",,,,
,PMC,Alphacoronavirus Transmissible Gastroenteritis Virus nsp1 Protein Suppresses Protein Translation in Mammalian Cells and in Cell-Free HeLa Cell Extracts but Not in Rabbit Reticulocyte Lysate,http://dx.doi.org/10.1128/JVI.01806-10,PMC3014157,,,"The nsp1 protein of transmissible gastroenteritis virus (TGEV), an alphacoronavirus, efficiently suppressed protein synthesis in mammalian cells. Unlike the nsp1 protein of severe acute respiratory syndrome coronavirus, a betacoronavirus, the TGEV nsp1 protein was unable to bind 40S ribosomal subunits or promote host mRNA degradation. TGEV nsp1 also suppressed protein translation in cell-free HeLa cell extract; however, it did not affect translation in rabbit reticulocyte lysate (RRL). Our data suggested that HeLa cell extracts and cultured host cells, but not RRL, contain a host factor(s) that is essential for TGEV nsp1-induced translational suppression.",,"['Huang, Cheng', 'Lokugamage, Kumari G.', 'Rozovics, Janet M.', 'Narayanan, Krishna', 'Semler, Bert L.', 'Makino, Shinji']",,,,
,PMC,Long range interaction networks in the function and fidelity of poliovirus RNA-dependent RNA polymerase studied by nuclear magnetic resonance,http://dx.doi.org/10.1021/bi100833r,PMC2989882,,,"The fidelity of the poliovirus RNA-dependent RNA polymerase (3D(pol)) plays a direct role in the genomic evolution and pathogenesis of the virus. A single site mutation (Gly64Ser) that is remote from the catalytic center results in a higher fidelity polymerase. NMR studies with [methyl-(13)C]methionine-labeled protein were used to compare the solution structure and dynamics of wild-type and Gly64Ser 3D(pol). The chemical shifts for the Met6 resonance were significantly different between wild-type and Gly64Ser 3D(pol) when bound in ternary complexes with RNA and incorrect, but not with correct, nucleotide, suggesting that the Gly64Ser mutation induces structural changes in the N-terminal β-strand when the enzyme is bound to incorrect, but not correct nucleotide. We also observe changes in the transverse relaxation times for methionines near regions important for nucleotide and RNA binding, and catalysis. Our strategy to assign the [methyl-(13)C]methionine resonances involved separately mutating each of the seventeen methionines. Several substitutions produced additional resonances for both Met6 and Met187, a reporter for RNA binding and conformational changes in the highly conserved motif B loop, even though these methionines are greater than 20 Å apart. The results for Gly64Ser and the other mutants are intriguing considering that they can result in structural and/or dynamic changes to methionines distant from the site of mutation. We propose that there is a long-distance network operating throughout 3D(pol) that coordinates ligand binding, conformational changes and catalysis. Mutation of Gly64 results in structural and/or dynamic changes to the network that may affect polymerase fidelity.",,"['Yang, Xiaorong', 'Welch, Jesse L.', 'Arnold, Jamie J.', 'Boehr, David D.']",,,,
,PMC,Functional Invariant NKT Cells in Pig Lungs Regulate the Airway Hyperreactivity: A Potential Animal Model,http://dx.doi.org/10.1007/s10875-010-9476-4,PMC4450678,,,"Important roles played by invariant natural killer T (iNKT) cells in asthma pathogenesis have been demonstrated. We identified functional iNKT cells and CD1d molecules in pig lungs. Pig iNKT cells cultured in the presence of α-GalCer proliferated and secreted Th1 and Th2 cytokines. Like in other animal models, direct activation of pig lung iNKT cells using α-GalCer resulted in acute airway hyperreactivity (AHR). Clinically, acute AHR-induced pigs had increased respiratory rate, enhanced mucus secretion in the airways, fever, etc. In addition, we observed petechial hemorrhages, infiltration of CD4(+) cells, and increased Th2 cytokines in AHR-induced pig lungs. Ex vivo proliferated iNKT cells of asthma induced pigs in the presence of C-glycoside analogs of α-GalCer had predominant Th2 phenotype and secreted more of Th2 cytokine, IL-4. Thus, baby pigs may serve as a useful animal model to study iNKT cell-mediated AHR caused by various environmental and microbial CD1d-specific glycolipid antigens.",,"['Renukaradhya, Gourapura J.', 'Manickam, Cordelia', 'Khatri, Mahesh', 'Rauf, Abdul', 'Li, Xiangming', 'Tsuji, Moriya', 'Rajashekara, Gireesh', 'Dwivedi, Varun']",,,,
,PMC,Detection of Excess Influenza Severity: Associating Respiratory Hospitalization and Mortality Data With Reports of Influenza-Like Illness by Primary Care Physicians,http://dx.doi.org/10.2105/AJPH.2009.168245,PMC2951970,,,"Objectives. We explored whether excesses in influenza severity can be detected by combining respiratory syndromic hospital and mortality data with data on influenza-like illness (ILI) cases obtained from general practitioners. Methods. To identify excesses in the severity of influenza infections in the population of the Netherlands between 1999 and 2005, we looked for increases in influenza-associated hospitalizations and mortality that were disproportionate to the number of ILI cases reported by general practitioners. We used generalized estimating equation regression models to associate syndromic hospital and mortality data with ILI surveillance data obtained from general practitioners. Virus isolation and antigenic characterization data were used to interpret the results. Results. Disproportionate increases in hospitalizations and mortality (relative to ILI cases reported by general practitioners) were identified in 2003/04 during the A/Fujian/411/02(H3N2) drift variant epidemic. Conclusions. Combined surveillance of respiratory hospitalizations and mortality and ILI data obtained from general practitioners can capture increases in severe influenza-associated illness that are disproportionate to influenza incidence rates. Therefore, this novel approach should complement traditional seasonal and pandemic influenza surveillance in efforts to detect increases in influenza case fatality rates and percentages of patients hospitalized.",,"['van den Wijngaard, Cees C.', 'van Asten, Liselotte', 'Meijer, Adam', 'van Pelt, Wilfrid', 'Nagelkerke, Nico J. D.', 'Donker, Gé A.', 'van der Sande, Marianne A. B.', 'Koopmans, Marion P. G.']",,,,
,PMC,A Multi-function Public Health Surveillance System and the Lessons Learned in Its Development: The Alberta Real Time Syndromic Surveillance Net,http://dx.doi.org/10.1007/BF03403963,PMC6973652,,,"Objective: We describe a centralized automated multi-function detection and reporting system for public health surveillance–the Alberta Real Time Syndromic Surveillance Net (ARTSSN). This improves upon traditional paper-based systems which are often fragmented, limited by incomplete data collection and inadequate analytical capacity, and incapable of providing timely information for public health action. Methods: ARTSSN concurrently analyzes multiple electronic data sources in real time to describe results in tables, charts and maps. Detected anomalies are immediately disseminated via alerts to decision-makers for action. Results: ARTSSN provides richly integrated information on a variety of health conditions for early detection of and prompt action on abnormal events such as clusters, outbreaks and trends. Examples of such health conditions include chronic and communicable disease, injury and environmentmediated adverse incidents. Discussion: Key advantages of ARTSSN over traditional paper-based methods are its timeliness, comprehensiveness and automation. Public health surveillance of communicable disease, injury, environmental hazard exposure and chronic disease now occurs in a single system in real time year round. Examples are given to demonstrate the public health value of this system, particularly during Pandemic (H1N1) 2009.",,"['Fan, Shihe', 'Blair, Corinne', 'Brown, Angela', 'Gabos, Stephan', 'Honish, Lance', 'Hughes, Trina', 'Jaipaul, Joy', 'Johnson, Marcia', 'Lo, Eric', 'Lubchenko, Anna', 'Mashinter, Laura', 'Meurer, David P.', 'Nardelli, Vanessa', 'Predy, Gerry', 'Shewchuk, Liz', 'Sosin, Daniel', 'Wicentowich, Bryan', 'Talbot, James']",,,,
,PMC,Gross postmortem and histologic examination findings from abortion losses and calf mortalities in western Canadian beef herds,,PMC2957030,,,"Production losses from abortions, stillbirths, and early calf mortality were described for the 2002 calf crop in 203 beef herds in western Canada. A total of 1689 calves were examined. A summary diagnosis was reported for 64% of aborted calves, 78% of stillborn calves, 88% of neonatal calves, and 94% of the calves > 3 d of age. Diagnoses for aborted calves included: thyroid gland lesions, pneumonia, developmental anomalies, placentitis, and myocardial necrosis or myopathy. For stillborn calves, diagnostic findings included: dystocia, thyroid gland lesions, myocardial necrosis or myopathy, developmental anomalies, and skeletal myopathy or necrosis. The most common diagnoses for neonatal calves (≤ 3 d) were: pneumonia, skeletal myopathy or necrosis, myocardial necrosis or myopathy, accident or trauma, and septicemia. For older calves (3 d to 3 mo), the most common diagnoses included: starvation, abomasal ulcer or perforation, enteritis or colitis, pneumonia, and intestinal volvulus, obstruction, or perforation.",,"['Waldner, Cheryl L.', 'Kennedy, Richard I.', 'Rosengren, Leigh B.', 'Pollock, Colleen M.', 'Clark, Edward (Ted) G.']",,,,
,PMC,The effective reproduction number of pandemic influenza: Prospective estimation,http://dx.doi.org/10.1097/EDE.0b013e3181f20977,PMC3084966,,,"BACKGROUND: Timely estimation of the transmissibility of a novel pandemic influenza virus was a public health priority in 2009. METHODS: We extended methods for prospective estimation of the effective reproduction number, (R(t)), over time in an emerging epidemic to allow for reporting delays and repeated importations. We estimated R(t) based on case notifications and hospitalizations associated with laboratory-confirmed pandemic (H1N1) 2009 virus infections in Hong Kong from June through October 2009 RESULTS: R(t) declined from around 1.4–1.5 at the start of the local epidemic to around 1.1–1.2 later in the summer, suggesting changes in transmissibility perhaps related to school vacations or seasonality. Estimates of R(t) based on hospitalizations of confirmed H1N1 cases closely matched estimates based on case notifications. CONCLUSION: Real-time monitoring of the effective reproduction number is feasible and can provide useful information to public health authorities for situational awareness and calibration of mitigation strategies.",,"['Cowling, Benjamin J.', 'Lau, Max S. Y.', 'Ho, Lai-Ming', 'Chuang, Shuk-Kwan', 'Tsang, Thomas', 'Liu, Shao-Haei', 'Leung, Pak-Yin', 'Lo, Su-Vui', 'Lau, Eric H. Y.']",,,,
,PMC,Challenges and Opportunities for New Protein Crystallization Strategies in Structure-Based Drug Design,http://dx.doi.org/10.1517/17460441.2010.515583,PMC2992350,,,"Structure-based drug design (SBDD) has emerged as a valuable pharmaceutical lead discovery tool, showing potential for accelerating the discovery process, while reducing developmental costs and boosting potencies of the drug that is ultimately selected. SBDD is a iterative, rational, lead compound sculpting process that involves both the synthesis of new derivatives and the evaluation of their binding to the target structure either through computational docking or elucidation of the target structure as a complex with the lead compound. This method heavily relies on the production of high-resolution (< 2Å) three-dimensional structures of the drug target, obtained through X-ray crystallographic analysis, in the presence or absence of the drug candidate. The lack of generalized methods for high quality crystal production is still a major bottleneck in the process of macromolecular crystallization. This review provides a brief introduction to SBDD and describes several macromolecular crystallization strategies, with an emphasis on advances and challenges facing researchers in the field today. Recent trends in the development of more universal macromolecular crystallization techniques, particularly nucleation-based techniques that are applicable to both soluble and integral membrane proteins, are also discussed.",,"['Grey, Jessica', 'Thompson, David']",,,,
,PMC,The infectious march: the complex interaction between microbes and the immune system in asthma,http://dx.doi.org/10.1016/j.iac.2010.09.008,PMC2992980,,,"There has been significant progress in our knowledge about the relationship between infectious disease and the immune system in relation to asthma, but many unanswered questions still remain. Respiratory tract infections such as those caused by respiratory syncytial virus and rhinovirus during the first two years of life are still clearly associated with later wheezing and asthma, but the mechanism has not been completely worked out. Is there an ‘infectious march’ triggered by infection in infancy that progresses to disease pathology or are infants who contract respiratory infections predisposed to developing asthma? This review focuses on the common themes in the interaction between microbes and the immune system and presents a critical appraisal of the evidence to date. The various mechanisms whereby microbes alter the immune response and how this might influence asthma are discussed along with new and promising clinical practices for prevention and therapy. Recent advances in utilizing sensitive PCR detection methods have allowed more rigorous testing of the causality hypothesis of virus infection leading to asthma, but the evidence is still equivocal. Various exceptions and inconsistencies in the clinical trials are discussed in light of new guidelines for subject inclusion/exclusion in hopes of providing some standardization. In spite of past failures in vaccination and disappointing results of some clinical trials, the new strategies for prophylaxis including RNA interference and targeted delivery of microbicides offer a large dose of hope to a world suffering from an increasing incidence of asthma and a huge burden of healthcare cost and loss of quality of life.",,"['Wong, Terianne', 'Hellermann, Gary', 'Mohapatra, Shyam']",,,,
,PMC,Viral diversity in asthma: Immunology and Allergy Clinics of North America: Asthma and Infectious Disease,http://dx.doi.org/10.1016/j.iac.2010.08.001,PMC2967440,,,"Asthma exacerbations are precipitated primarily by respiratory virus infection and frequently require immediate medical intervention. Studies of childhood and adult asthma have implicated a wide variety of respiratory viruses in exacerbations. By focusing on both RNA and DNA respiratory viruses and some newly identified viruses, this review illustrates the diversity and highlights some of the uncertainties that exist in our understanding of virus-related asthma exacerbations.",,"['McErlean, Peter', 'Greiman, Alyssa', 'Favoreto, Silvio', 'Avila, Pedro C.']",,,,
,PMC,An Observational Assessment Method for Aging Laboratory Rats,,PMC2994044,,,"The rapid growth of the aging human population highlights the need for laboratory animal models to study the basic biologic processes of aging and susceptibility to disease, drugs, and environmental pollutants. Methods are needed to evaluate the health of aging animals over time, particularly methods for efficiently monitoring large research colonies. Here we describe an observational assessment method that scores appearance, posture, mobility, and muscle tone on a 5-point scale that can be completed in about 1 min. A score of 1 indicates no deterioration, whereas a score of 5 indicates severe deterioration. Tests were applied to male Brown Norway rats between 12 and 36 mo of age (n = 32). The rats were participating concurrently in experiments on the behavioral effects of intermittent exposure (approximately every 4 mo) to short-acting environmental chemicals. Results demonstrated that aging-related signs of deterioration did not appear before 18 mo of age. Assessment scores and variability then increased with age. Body weights increased until approximately 24 mo, then remained stable, but decreased after 31 mo for the few remaining rats. The incidence of death increased slightly from 20 to 28 mo of age and then rose sharply; median survival age was approximately 30 mo, with a maximum of 36 mo. The results indicate that our observational assessment method supports efficient monitoring of the health of aging rats and may be useful in studies on susceptibility to diseases, drugs, and toxicants during old age.",,"['Phillips, Pamela M', 'Jarema, Kimberly A', 'Kurtz, David M', 'MacPhail, Robert C']",,,,
,PMC,Anti-dsDNA Antibodies Bind to Mesangial Annexin II in Lupus Nephritis,http://dx.doi.org/10.1681/ASN.2009080805,PMC3014006,,,"Production of anti-dsDNA antibodies is a hallmark of lupus nephritis, but how these antibodies deposit in organs and elicit inflammatory damage remains unknown. In this study, we sought to identify antigens on the surface of human mesangial cells (HMC) that mediate the binding of human anti-dsDNA antibodies and the subsequent pathogenic processes. We isolated anti-dsDNA antibodies from patients with lupus nephritis by affinity chromatography. We used multiple methods to identify and characterize antigens from the plasma membrane fraction of mesangial cells that crossreacted with the anti-dsDNA antibodies. We found that annexin II mediated the binding of anti-dsDNA antibodies to HMC. After binding to the mesangial cell surface, anti-dsDNA antibodies were internalized into the cytoplasm and nucleus. This also led to induction of IL-6 secretion and annexin II synthesis, mediated through activation of p38 MAPK, JNK, and AKT. Binding of anti-dsDNA antibodies to annexin II correlated with disease activity in human lupus nephritis. Glomerular expression of annexin II correlated with the severity of nephritis, and annexin II colocalized with IgG and C3 deposits in both human and murine lupus nephritis. Gene silencing of annexin II in HMC reduced binding of anti-dsDNA antibody and partially decreased IL-6 secretion. In summary, our data demonstrate that annexin II mediates the binding of anti-dsDNA antibodies to mesangial cells, contributing to the pathogenesis of lupus nephritis. This interaction provides a potential target for therapeutic intervention.",,"['Yung, Susan', 'Cheung, Kwok Fan', 'Zhang, Qing', 'Chan, Tak Mao']",,,,
,PMC,Massively parallel sequencing for monitoring genetic consistency and quality control of live viral vaccines,http://dx.doi.org/10.1073/pnas.1012537107,PMC2993378,,,"Intrinsic genetic instability of RNA viruses may lead to the accumulation of revertants during manufacture of live viral vaccines, requiring rigorous quality control to ensure vaccine safety. Each lot of oral poliovirus vaccine (OPV) is tested for neurovirulence in animals and also for the presence of neurovirulent revertants. Mutant analysis by PCR and restriction enzyme cleavage (MAPREC) is used to measure the frequency of neurovirulent mutations at the 5′ untranslated region (UTR) of the viral genome that correlate with the level of neurovirulence determined by the monkey neurovirulence test. However, MAPREC can only monitor mutations at a few genomic loci and miss mutations at other sites that could adversely affect vaccine quality. Here we propose to use massively parallel sequencing (MPS) for sensitive detection and quantification of all mutations in the entire genome of attenuated viruses. Analysis of vaccine samples and reference preparations demonstrated a perfect agreement with MAPREC results. Quantitative MPS analysis of validated reference preparations tested by MAPREC produced identical results, suggesting that the method could take advantage of the existing reference materials and be used as a replacement for the MAPREC procedure in lot release of OPV. Patterns of mutations present at a low level in vaccine preparations were characteristic of seed viruses used for their manufacture and could be used for identification of individual batches. This approach may represent the ultimate tool for monitoring genetic consistency of live viral vaccines.",,"['Neverov, Alexander', 'Chumakov, Konstantin']",,,,
,PMC,RNA helicases: Emerging roles in viral replication and the host innate response,http://dx.doi.org/10.4161/rna.7.6.14249,PMC3073335,,,"RNA helicases serve multiple roles at the virus-host interface. In some situations, RNA helicases are essential host factors to promote viral replication; however, in other cases they serve as a cellular sensor to trigger the antiviral state in response to viral infection. All family members share the conserved ATP-dependent catalytic core linked to different substrate recognition and protein-protein interaction domains. These flanking domains can be shuffled between different helicases to achieve functional diversity. This review summarizes recent studies, This review summarizes recent studies of RNA helicases in virus biology. First, RNA helicases are catalysts of progressive RNA-protein rearrangements that begin at gene transcription and culminate in release of infectious virus. Second, RNA helicases can act as a scaffold for alternative protein-protein interactions that can defeat the antiviral state. The mounting fundamental understanding of RNA helicases is being used to develop selective and efficacious drugs against human and animal pathogens. The analysis of RNA helicases in virus model systems continues to provide insights into virology, cell biology and immunology and has provided fresh perspective to continue unraveling the complexity of virus-host interactions.",,"['Ranji, Arnaz', 'Boris-Lawrie, Kathleen']",,,,
,PMC,The twenty-nine amino acid C-terminal cytoplasmic domain of poliovirus 3AB is critical for nucleic acid chaperone activity,http://dx.doi.org/10.4161/rna.7.6.13781,PMC3072266,,,"Poliovirus 3AB protein is the first picornavirus protein demonstrated to have nucleic acid chaperone activity. Further characterization of 3AB demonstrates that the C-terminal 22 amino acids (3B region (also referred to as VPg), amino acid 88–109) of the protein is required for chaperone activity, as mutations in this region abrogate nucleic acid binding and chaperone function. Protein 3B alone has no chaperone activity as determined by established assays that include the ability to stimulate nucleic acid hybridization in a primer-template annealing assay, helix-destabilization in a nucleic acid unwinding assay or aggregation of nucleic acids. In contrast, the putative 3AB C-terminal cytoplasmic domain (C terminal amino acids 81–109, 3B + the last 7 C-terminal amino acids of 3A, termed 3B+7 in this report) possesses strong activity in these assays, albeit at much higher concentrations than 3AB. The characteristics of several mutations in 3B+7 are described here, as well as a model proposing that 3B+7 is the site of the “intrinsic” chaperone activity of 3AB while the 3A N-terminal region (amino acids 1–58) and/or membrane anchor domain (amino acids 59–80) serve to increase the effective concentration of the 3B+7 region leading to the potent chaperone activity of 3AB.",,"['Gangaramani, Divya R', 'Eden, Elizabeth L', 'Shah, Manthan', 'DeStefano, Jeffrey J']",,,,
,PMC,Human basophils express amphiregulin in response to T cell-derived IL-3,http://dx.doi.org/10.1016/j.jaci.2010.08.040,PMC2998547,,,"BACKGROUND: Amphiregulin, a member of the Epidermal Growth Factor family, is expressed by activated mouse Th2 cells. Amphiregulin produced by mouse hematopoietic cells contributes to the elimination of a nematode infection by a Type 2 effector response. OBJECTIVE: To identify the human peripheral blood cell population expressing amphiregulin. METHODS: Amphiregulin-expressing cells were identified by flow cytometry of cell surface markers and histological staining. Histamine and amphiregulin in supernatants were measured by enzyme immunoassay. Quantitative real-time PCR was used to measure mRNA expression. RESULTS: Stimulation of human peripheral blood mononuclear cells by anti-CD3 + anti-CD28 antibodies induced expression of amphiregulin mRNA and protein by a non-T cell population. The amphiregulin-producing cells were basophils, as judged by morphology and expression of CD203c and CD123 (IL-3 receptor alpha chain). Activated mouse basophils also produced amphiregulin. Amphiregulin expression by basophils in response to anti-TCR stimulation required IL-3 produced by T cells, and IL-3 alone induced high levels of amphiregulin expression by purified basophils. Amphiregulin was expressed at much higher levels when human basophils were stimulated by IL-3 than by IgE cross-linking, whereas the opposite was true for IL-4 expression and histamine release. Heparin-binding Epidermal Growth Factor-like growth factor was also expressed by IL-3-stimulated human basophils. PBMC from asthmatic human subjects contained significantly higher numbers of basophils able to produce amphiregulin, compared to allergic or non-allergic controls. CONCLUSION: IL-3 can induce basophils to express high levels of amphiregulin, which may contribute to tissue remodeling during type 2 immune responses such as asthma.",,"['Qi, Yilin', 'Operario, Darwin J.', 'Oberholzer, Chris M.', 'Kobie, James J.', 'Looney, R. John', 'Georas, Steve N.', 'Mosmann, Tim R.']",,,,
,PMC,Antiviral Activities of ISG20 in Positive-strand RNA Virus Infections,http://dx.doi.org/10.1016/j.virol.2010.10.008,PMC3018280,,,"ISG20 is an interferon-inducible 3′-5′ exonuclease that inhibits replication of several human and animal RNA viruses. However, the specificities of ISG20’s antiviral action remain poorly defined. Here we determine the impact of ectopic expression of ISG20 on replication of several positive-strand RNA viruses from distinct viral families. ISG20 inhibited infections by cell culture-derived hepatitis C virus (HCV) and a pestivirus, bovine viral diarrhea virus and a picornavirus, hepatitis A virus. Moreover, ISG20 demonstrated cell-type specific antiviral activity against yellow fever virus, a classical flavivirus. Overexpression of ISG20, however, did not inhibit propagation of severe acute respiratory syndrome coronavirus, a highly-pathogenic human coronavirus in Huh7.5 cells. The antiviral effects of ISG20 were all dependent on its exonuclease activity. The closely related cellular exonucleases, ISG20L1 and ISG20L2, did not inhibit HCV replication. Together, these data may help better understand the antiviral specificity and action of ISG20.",,"['Zhou, Zhi', 'Wang, Nan', 'Woodson, Sara E.', 'Dong, Qingming', 'Wang, Jie', 'Liang, Yuqiong', 'Rijnbrand, Rene', 'Wei, Lai', 'Nichols, Joan E.', 'Guo, Ju-Tao', 'Holbrook, Michael R.', 'Lemon, Stanley M.', 'Li, Kui']",,,,
,PMC,Carcinoembryonic antigen-related cell adhesion molecule-1 regulates granulopoiesis by inhibition of granulocyte-colony stimulating factor receptor,http://dx.doi.org/10.1016/j.immuni.2010.10.009,PMC3765078,,,"Although carcinoembryonic antigen-related cell adhesion moclecule-1 (CEACAM1) is an activation marker for neutrophils and delays neutrophil apoptosis, the role of CEACAM1 in granulopoiesis and neutrophil dependent host immune responses has not been investigated. CEACAM1 expression correlated with granulocytic differentiation, and Ceacam1(−/−) mice developed neutrophilia due to loss of the Src- homology-phosphatase-1 (SHP-1) dependent inhibition of granulocyte-colony stimulating factor receptor (G-CSFR)-signal transducer and activator of transcription (Stat3) pathway provided by CEACAM1. Moreover, Ceacam1(−/−) mice were hypersensitive to Listeria Monocytogenes (LM) infection with an accelerated mortality. Reintroduction of CEACAM1 into Ceacam1(−/−) bone marrow restored normal granulopoiesis and host sensitivity to LM infection, while mutation of its immunoreceptor tyrosine-based inhibitory motifs (ITIMs) abrogated this restoration. shRNA mediated reduction of Stat3 amounts rescued normal granulopoiesis attenuating host sensitivity to LM infection in Ceacam1(−/−) mice. Thus, CEACAM1 acted as a co-inhibitory receptor for G-CSFR regulating granulopoiesis and host innate immune response to bacterial infections.",,"['Pan, Hao', 'Shively, John E.']",,,,
,PMC,From Vaccines to Memory and Back,http://dx.doi.org/10.1016/j.immuni.2010.10.008,PMC3760154,,,Vaccines work by eliciting an immune response and consequent immunological memory that mediates protection from infection or disease. Recently new methods have been developed to dissect the immune response in experimental animals and humans which have led to increased understanding of the molecular mechanisms that control differentiation and maintenance of memory T and B cells. In this review we will provide an overview of the cellular organization of immune memory and underline some of the outstanding questions on immunological memory and how they pertain to vaccination strategies. Finally we will discuss how we can learn about antigen design from the interrogation of our memory T and B cells – a journey from vaccines to memory and back.,,"['Sallusto, Federica', 'Lanzavecchia, Antonio', 'Araki, Koichi', 'Ahmed, Rafi']",,,,
,PMC,Vaccination Strategies to Promote Mucosal Antibody Responses,http://dx.doi.org/10.1016/j.immuni.2010.09.013,PMC3045856,,,"There are great interest and demand for the development of vaccines to prevent and treat diverse microbial infections. Mucosal vaccines elicit immune protection by stimulating the production of antibodies at mucosal surfaces and systemic districts. Being positioned in close proximity to a large community of commensal microbes, the mucosal immune system deploys a heterogeneous population of cells and a complex regulatory network to maintain the balance between surveillance and tolerance. A successful mucosal vaccine relies on leveraging the functions of these immune cells and regulatory components. This article reviews the important cellular interactions and molecular pathways underlying the induction and regulation of mucosal antibody responses and discusses their implications on mucosal vaccination.",,"['Chen, Kang', 'Cerutti, Andrea']",,,,
,PMC,"Deficient Incorporation of Spike Protein into Virions Contributes to the Lack of Infectivity Following Establishment of a Persistent, Non-Productive Infection in Oligodendroglial Cell Culture by Murine Coronavirus",http://dx.doi.org/10.1016/j.virol.2010.10.006,PMC3032362,,,"Infection of mouse oligodendrocytes with a recombinant mouse hepatitis virus (MHV) expressing a green fluorescence protein facilitated specific selection of virus-infected cells and subsequent establishment of persistence. Interestingly, while viral genomic RNAs persisted in infected cells over 14 subsequent passages with concomitant synthesis of viral subgenomic mRNAs and structural proteins, no infectious virus was isolated beyond passage 2. Further biochemical and electron microscopic analyses revealed that virions, while assembled, contained little spike in the envelope, indicating that lack of infectivity during persistence was likely due to deficiency in spike incorporation. This type of non-lytic, non-productive persistence in oligodendrocytes is unique among animal viruses and resembles MHV persistence previously observed in the mouse central nervous system. Thus, establishment of such a culture system that can recapitulate the in vivo phenomenon will provide a powerful approach for elucidating the mechanisms of coronavirus persistence in glial cells at the cellular and molecular levels.",,"['Liu, Yin', 'Herbst, Werner', 'Cao, Jianzhong', 'Zhang, Xuming']",,,,
,PMC,Association of Seropositivity for Influenza and Coronaviruses with History of Mood Disorders and Suicide Attempts,http://dx.doi.org/10.1016/j.jad.2010.09.029,PMC3043161,,,"BACKGROUND: Anecdotal reports of mood disorder following infection with common respiratory viruses with neurotropic potential have been in existence since the last century. Nevertheless, systematic studies on the association between these viruses and mood disorders are lacking. METHODS: Influenza A, B and coronavirus antibody titers were measured in 257 subjects with recurrent unipolar and bipolar disorder and healthy controls, by SCID. Pearson’s χ(2) tests and logistic regression models were used to analyze associations between seropositivity for coronaviruses, influenza A and B viruses and the following: a) history of recurrent mood disorders b) having attempted suicide in the past c) uni- vs. bi-polarity and d) presence of psychotic features during mood episodes. RESULTS: Seropositivity for influenza A (p=0.004), B (p<0.0001) and coronaviruses (p<0.0001) were associated with history of mood disorders but not with the specific diagnosis of unipolar or bipolar depression. Seropositivity for influenza B was significantly associated with a history of suicide attempt (p =0.001) and history of psychotic features (p =0.005). LIMITATIONS: The design was cross-sectional Socioeconomic factors, inflammatory markers, and axis II psychopathology were not assessed. CONCLUSIONS: The association of seropositivity for influenza and coronaviruses with a history of mood disorders, and influenza B with suicidal behavior require replication in larger longitudinal samples. The need for these studies is additionally supported by the high incidence of these viral infections, the high prevalence of mood disorders, and resilience of suicide epidemics.",,"['Okusaga, Olaoluwa', 'Yolken, Robert H.', 'Langenberg, Patricia', 'Lapidus, Manana', 'Arling, Timothy A.', 'Dickerson, Faith B.', 'Scrandis, Debra A.', 'Severance, Emily', 'Cabassa, Johanna A.', 'Balis, Theodora', 'Postolache, Teodor T.']",,,,
,PMC,TLR-activated dendritic cells enhance the response of aged naïve CD4 T cells via an IL-6 dependent mechanism(),http://dx.doi.org/10.4049/jimmunol.0901296,PMC3375592,,,"The most effective immunological adjuvants contain microbial products, such as toll like receptor (TLR) agonists, which bind to conserved pathogen-associated recognition receptors. These activate dendritic cells (DC) to become highly effective antigen-presenting cells (APC). We assessed whether TLR ligand-treated DC can enhance the otherwise defective response of aged naïve CD4 T cells. In vivo administration of CpG, PolyI:C and Pam(3)CSK(4) in combination with antigen resulted in the increased expression of costimulatory molecules and MHC class II by dendritic cells (DC), elevated serum levels of the inflammatory cytokines IL-6 and RANTES, and increased cognate CD4 T cell responses in young and aged mice. We show that in vitro, pre-activation of DC by TLR ligands makes them more efficient APC for aged naïve CD4 T cells. Following T:DC interaction, there are enhanced production of inflammatory cytokines, particularly IL-6, and greater expansion of the aged T cells, resulting from increased proliferation and greater effector survival with increased levels of Bcl-2. TLR pre-activation of both bone marrow derived and ex vivo DC improved responses. IL-6 produced by the activated DC during cognate T cell interaction was necessary for enhanced aged CD4 T cell expansion and survival. These studies suggest that some age-associated immune defects may be overcome by targeted activation of APC by TLR ligands.",,"['Jones, Stephen C.', 'Brahmakshatriya, Vinayak', 'Huston, Gail', 'Dibble, John', 'Swain, Susan L.']",,,,
,PMC,Template Recognition Mechanisms by Replicase Proteins Differ between Bipartite Positive-Strand Genomic RNAs of a Plant Virus,http://dx.doi.org/10.1128/JVI.01754-10,PMC3014169,,,"Recognition of RNA templates by viral replicase proteins is one of the key steps in the replication process of all RNA viruses. However, the mechanisms underlying this phenomenon, including primary RNA elements that are recognized by the viral replicase proteins, are not well understood. Here, we used aptamer pulldown assays with membrane fractionation and protein-RNA coimmunoprecipitation in a cell-free viral translation/replication system to investigate how viral replicase proteins recognize the bipartite genomic RNAs of the Red clover necrotic mosaic virus (RCNMV). RCNMV replicase proteins bound specifically to a Y-shaped RNA element (YRE) located in the 3′ untranslated region (UTR) of RNA2, which also interacted with the 480-kDa replicase complexes that contain viral and host proteins. The replicase-YRE interaction recruited RNA2 to the membrane fraction. Conversely, RNA1 fragments failed to interact with the replicase proteins supplied in trans. The results of protein-RNA coimmunoprecipitation assays suggest that RNA1 interacts with the replicase proteins coupled with their translation. Thus, the initial template recognition mechanisms employed by the replicase differ between RCNMV bipartite genomic RNAs and RNA elements are primary determinants of the differential replication mechanism.",,"['Iwakawa, Hiro-oki', 'Mine, Akira', 'Hyodo, Kiwamu', 'An, Mengnan', 'Kaido, Masanori', 'Mise, Kazuyuki', 'Okuno, Tetsuro']",,,,
,PMC,Successful Vaccination Strategies That Protect Aged Mice from Lethal Challenge from Influenza Virus and Heterologous Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.01805-10,PMC3014161,,,"Newly emerging viruses often circulate as a heterogeneous swarm in wild animal reservoirs prior to their emergence in humans, and their antigenic identities are often unknown until an outbreak situation. The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) and reemerging influenza virus cause disproportionate disease in the aged, who are also notoriously difficult to successfully vaccinate, likely due to immunosenescence. To protect against future emerging strains, vaccine platforms should induce broad cross-reactive immunity that is sufficient to protect from homologous and heterologous challenge in all ages. From initial studies, we hypothesized that attenuated Venezuelan equine encephalitis virus (VEE) replicon particle (VRP) vaccine glycoproteins mediated vaccine failure in the aged. We then compared the efficacies of vaccines bearing attenuated (VRP(3014)) or wild-type VEE glycoproteins (VRP(3000)) in young and aged mice within novel models of severe SARS-CoV pathogenesis. Aged animals receiving VRP(3000)-based vaccines were protected from SARS-CoV disease, while animals receiving the VRP(3014)-based vaccines were not. The superior protection for the aged observed with VRP(3000)-based vaccines was confirmed in a lethal influenza virus challenge model. While the VRP(3000) vaccine's immune responses in the aged were sufficient to protect against lethal homologous and heterologous challenge, our data suggest that innate defects within the VRP(3014) platform mediate vaccine failure. Exploration into the mechanism(s) of successful vaccination in the immunosenescent should aid in the development of successful vaccine strategies for other viral diseases disproportionately affecting the elderly, like West Nile virus, influenza virus, norovirus, or other emerging viruses of the future.",,"['Sheahan, Timothy', 'Whitmore, Alan', 'Long, Kristin', 'Ferris, Martin', 'Rockx, Barry', 'Funkhouser, William', 'Donaldson, Eric', 'Gralinski, Lisa', 'Collier, Martha', 'Heise, Mark', 'Davis, Nancy', 'Johnston, Robert', 'Baric, Ralph S.']",,,,
,PMC,Respiratory tract immunization of non-human primates with a Newcastle disease virus-vectored vaccine against Ebola virus elicits a neutralizing antibody response,http://dx.doi.org/10.1016/j.vaccine.2010.10.024,PMC3428043,,,"We previously developed a respiratory tract vaccine against Ebola virus (EBOV) based on human parainfluenza virus type 3 (HPIV3), a respiratory paramyxovirus, expressing the EBOV GP envelope protein (HPIV3/GP) from an added gene. Two doses of this vaccine delivered by the intranasal and intratracheal route protected monkeys against intraperitoneal challenge with EBOV; however, concerns exist that the vaccine may have reduced immunogenicity in the adult human population due to pre-existing immunity against HPIV3. Here we developed a new vaccine (NDV/GP) based on Newcastle disease virus (NDV), an avian paramyxovirus that is antigenically distinct from human viral pathogens and is highly attenuated in monkeys. Following one intranasal and intratracheal inoculation of Rhesus monkeys with NDV/GP, titers of EBOV-specific antibodies in respiratory tract secretions and serum samples determined by ELISA, as well as serum EBOV-neutralizing antibodies, were undetectable or low compared to those induced by HPIV3/GP. A second immunization resulted in a substantial boost in serum IgG ELISA titers, yet the titers remained lower than those induced by a second dose of HPIV3/GP. In contrast, the ELISA IgA titers in respiratory tract secretions and, more importantly, the serum EBOV-neutralizing antibody titers were equal to those induced after the second dose of HPIV3/GP. These data suggest that NDV/GP can be effective for immunization against EBOV alone, or in combination with either HPIV3/GP or another vaccine platform in a heterologous prime-boost regimen.",,"['DiNapoli, Joshua M.', 'Yang, Lijuan', 'Samal, Siba K.', 'Murphy, Brian R.', 'Collins, Peter L.', 'Bukreyev, Alexander']",,,,
,PMC,The Nucleolus under Stress,http://dx.doi.org/10.1016/j.molcel.2010.09.024,PMC2987465,20965417,CC BY,"Cells typically respond quickly to stress, altering their metabolism to compensate. In mammalian cells, stress signaling usually leads to either cell-cycle arrest or apoptosis, depending on the severity of the insult and the ability of the cell to recover. Stress also often leads to reorganization of nuclear architecture, reflecting the simultaneous inhibition of major nuclear pathways (e.g., replication and transcription) and activation of specific stress responses (e.g., DNA repair). In this review, we focus on how two nuclear organelles, the nucleolus and the Cajal body, respond to stress. The nucleolus senses stress and is a central hub for coordinating the stress response. We review nucleolar function in the stress-induced regulation of p53 and the specific changes in nucleolar morphology and composition that occur upon stress. Crosstalk between nucleoli and CBs is also discussed in the context of stress responses.",2010 Oct 22,"['Boulon, Séverine', 'Westman, Belinda J.', 'Hutten, Saskia', 'Boisvert, François-Michel', 'Lamond, Angus I.']",Mol Cell,,,
,PMC,Phylogenetic and gene-centric metagenomics of the canine intestinal microbiome reveals similarities with humans and mice,http://dx.doi.org/10.1038/ismej.2010.162,PMC3105739,,,"This study is the first to use a metagenomics approach to characterize the phylogeny and functional capacity of the canine gastrointestinal microbiome. Six healthy adult dogs were used in a crossover design and fed a low-fiber control diet (K9C) or one containing 7.5% beet pulp (K9BP). Pooled fecal DNA samples from each treatment were subjected to 454 pyrosequencing, generating 503 280 (K9C) and 505 061 (K9BP) sequences. Dominant bacterial phyla included the Bacteroidetes/Chlorobi group and Firmicutes, both of which comprised ∼35% of all sequences, followed by Proteobacteria (13–15%) and Fusobacteria (7–8%). K9C had a greater percentage of Bacteroidetes, Fusobacteria and Proteobacteria, whereas K9BP had greater proportions of the Bacteroidetes/Chlorobi group and Firmicutes. Archaea were not altered by diet and represented ∼1% of all sequences. All archaea were members of Crenarchaeota and Euryarchaeota, with methanogens being the most abundant and diverse. Three fungi phylotypes were present in K9C, but none in K9BP. Less than 0.4% of sequences were of viral origin, with >99% of them associated with bacteriophages. Primary functional categories were not significantly affected by diet and were associated with carbohydrates; protein metabolism; DNA metabolism; cofactors, vitamins, prosthetic groups and pigments; amino acids and derivatives; cell wall and capsule; and virulence. Hierarchical clustering of several gastrointestinal metagenomes demonstrated phylogenetic and metabolic similarity between dogs, humans and mice. More research is required to provide deeper coverage of the canine microbiome, evaluate effects of age, genetics or environment on its composition and activity, and identify its role in gastrointestinal disease.",,"['Swanson, Kelly S', 'Dowd, Scot E', 'Suchodolski, Jan S', 'Middelbos, Ingmar S', 'Vester, Brittany M', 'Barry, Kathleen A', 'Nelson, Karen E', 'Torralba, Manolito', 'Henrissat, Bernard', 'Coutinho, Pedro M', 'Cann, Isaac KO', 'White, Bryan A', 'Fahey, George C']",,,,
,PMC,"Deubiquitylase, DeSUMOylase, and DeISGylase Activity Microarrays for Assay of Substrate Preference and Functional Modifiers",http://dx.doi.org/10.1074/mcp.M110.002402,PMC3013450,,,"Microarray-based proteomics expanded the information potential of DNA arrays to the level of protein translation and interaction, but so far, not much beyond. Although enzymatic activity from immobilized proteins has been reliably studied using surface plasmon resonance, a microarray of catalytically competent enzymes would facilitate high throughput, parallel study of their function. The ability to localize activity from soluble substrates has frustrated development of such an array. Here, we report the novel use of previously developed, highly specific suicide substrates for three families of enzymes: deubiquitylases, deSUMOylases, and deISGylases. We show specificity of each family to its cognate substrate, and demonstrate utility of the array in a secondary screen of small molecule inhibitors.",,"['Loch, Christian M.', 'Cuccherini, Charles L.', 'Leach, Craig A.', 'Strickler, James E.']",,,,
,PMC,Transcription factor Sox11b is involved in spinal cord regeneration in adult zebrafish,http://dx.doi.org/10.1016/j.neuroscience.2010.10.026,PMC3292217,,,"Adult zebrafish have the ability to recover from spinal cord injury and exhibit re-growth of descending axons from the brainstem to the spinal cord. We performed gene expression analysis using microarray to find damage-induced genes after spinal cord injury, and found that Sox11b mRNA is up-regulated at 11 days after injury. However, the functional relevance of Sox11b for regeneration is not known. Here, we report that the up-regulation of Sox11b mRNA after spinal cord injury is mainly localized in ependymal cells lining the central canal and in newly differentiating neuronal precursors or immature neurons. Using an in vivo morpholino-based gene knockout approach, we demonstrate that Sox11b is essential for locomotor recovery after spinal cord injury. In the injured spinal cord, expression of the neural stem cell associated gene Nestin, and the proneural gene Ascl1a (Mash1a), which are involved in the self-renewal and cell fate specification of endogenous neural stem cells, respectively, is regulated by Sox11b. Our data indicate that Sox11b promotes neuronal determination of endogenous stem cells and regenerative neurogenesis following spinal cord injury in the adult zebrafish. Enhancing Sox11b expression to promote proliferation and neurogenic determination of endogenous neural stem cells after injury may be a promising strategy in restorative therapy after spinal cord injury in mammals.",,"['Guo, Yuji', 'Ma, Liping', 'Cristofanilli, Massimiliano', 'Hart, Ronald P', 'Hao, Aijun', 'Schachner, Melitta']",,,,
,PMC,Tetracycline compounds with non-antimicrobial organ protective properties: possible mechanisms of action,http://dx.doi.org/10.1016/j.phrs.2010.10.004,PMC3031662,,,"Tetracyclines were developed as a result of the screening of soil samples for antibiotics. The first(t) of these compounds, chlortetracycline, was introduced in 1947. Tetracyclines were found to be highly effective against various pathogens including rickettsiae, as well as both gram-positive and gram-negative bacteria, thus becoming the first class of broad spectrum antibiotics. Many other interesting properties, unrelated to their antibiotic activity, have been identified for tetracyclines which have led to widely divergent experimental and clinical uses. For example, tetracyclines are also an effective anti-malarial drug. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Another tetracycline, doxycycline is known to exert anti-protease activities. Doxycycline can inhibit matrix metalloproteinases which contribute to tissue destruction activities in diseases such as periodontitis. A large body of literature has provided additional evidence for the “beneficial” actions of tetracyclines, including their ability to act as reactive oxygen species scavengers and anti-inflammatory agents. This review provides a summary of tetracycline’s multiple mechanisms of action as a means to understand their beneficial effects.",,"['Griffin, Michael O.', 'Ceballos, Guillermo', 'Villarreal, Francisco']",,,,
,PMC,Prevalence of Antibodies to Four Human Coronaviruses Is Lower in Nasal Secretions than in Serum,http://dx.doi.org/10.1128/CVI.00278-10,PMC3008199,,,"Little is known about the prevalence of mucosal antibodies induced by infection with human coronaviruses (HCoV), including HCoV-229E and -OC43 and recently described strains (HCoV-NL63 and -HKU1). By enzyme-linked immunosorbent assay, we measured anti-HCoV IgG antibodies in serum and IgA antibodies in nasal wash specimens collected at seven U.S. sites from 105 adults aged 50 years and older (mean age, 67 ± 9 years) with chronic obstructive pulmonary disease. Most patients (95 [90%]) had at least one more chronic disease. More patients had serum antibody to each HCoV strain (104 [99%] had antibody to HCoV-229E, 105 [100%] had antibody to HCoV-OC43, 103 [98%] had antibody to HCoV-NL63, and 96 [91%] had antibody to HCoV-HKU1) than had antibody to each HCoV strain in nasal wash specimens (12 [11%] had antibody to HCoV-229E, 22 [22%] had antibody to HCoV-OC43, 8 [8%] had antibody to HCoV-NL63, and 31 [31%] had antibody to HCoV-HKU1), respectively (P < 0.0001). The proportions of subjects with IgA antibodies in nasal wash specimens and the geometric mean IgA antibody titers were statistically higher for HCoV-OC43 and -HKU1 than for HCoV-229E and -NL63. A higher proportion of patients with heart disease than not had IgA antibodies to HCoV-NL63 (6 [16%] versus 2 [3%]; P = 0.014). Correlations were highest for serum antibody titers between group I strains (HCoV-229E and -NL63 [r = 0.443; P < 0.0001]) and between group II strains (HCoV-OC43 and -HKU1 [r = 0.603; P < 0.0001]) and not statistically significant between HCoV-NL63 and -OC43 and between HCoV-NL63 and -HKU1. Patients likely had experienced infections with more than one HCoV strain, and IgG antibodies to these HCoV strains in serum were more likely to be detected than IgA antibodies to these HCoV strains in nasal wash specimens.",,"['Gorse, Geoffrey J.', 'Patel, Gira B.', 'Vitale, Joseph N.', ""O'Connor, Theresa Z.""]",,,,
,PMC,Microevolution of Canine Influenza Virus in Shelters and Its Molecular Epidemiology in the United States,http://dx.doi.org/10.1128/JVI.01350-10,PMC3004329,,,"Canine influenza virus (CIV) emerged around 2000 when an equine influenza virus (EIV) was transmitted to dogs in Florida. After 2003, the canine virus was carried by infected greyhounds to various parts of the United States and then became established in several large animal shelters, where it has continued to circulate. To better understand the evolution of CIV since its emergence, and particularly its microevolution in spatially restricted populations, we examined multiple gene segments of CIV from dogs resident in two large animal shelters in New York City during the period 2006 to 2009. In particular, we focused on viruses circulating in the two shelters in 2008 and 2009, which we found shared a common ancestor. While viruses in each shelter were generally monophyletic, we observed some gene flow between them. These shelter sequences were compared to earlier CIV isolates. The shelter viruses differed in 1 to 6 amino acids in each gene segment compared to viruses isolated in Florida between 2003 and 2005 and in Colorado in 2006 and 2008. A comparison of the sequences of equine and canine viruses revealed amino acid replacements that distinguished the viruses from the two hosts, but no clear evidence of positive selection indicative of host adaptation was detected, suggesting that any host range adaptation in CIV occurred early in the emergence of this virus or even before it transferred to dogs.",,"['Hayward, Jessica J.', 'Dubovi, Edward J.', 'Scarlett, Janet M.', 'Janeczko, Stephanie', 'Holmes, Edward C.', 'Parrish, Colin R.']",,,,
,PMC,MyD88 Signaling Is Indispensable for Primary Influenza A Virus Infection but Dispensable for Secondary Infection,http://dx.doi.org/10.1128/JVI.01675-10,PMC3004294,,,"Recent studies have revealed that innate immunity is involved in the development of adaptive immune responses; however, its role in protection is not clear. In order to elucidate the exact role of Toll-like receptor (TLR) or RIG-I-like receptor (RLR) signaling on immunogenicity and protective efficacy against influenza A virus infection (A/PR/8/34 [PR8]; H1N1), we adapted several innate signal-deficient mice (e.g., TRIF(−/−), MyD88(−/−), MyD88(−/−) TRIF(−/−), TLR3(−/−) TLR7(−/−), and IPS-1(−/−)). In this study, we found that MyD88 signaling was required for recruitment of CD11b(+) granulocytes, production of early inflammatory cytokines, optimal proliferation of CD4 T cells, and production of Th1 cytokines by T cells. However, PR8 virus-specific IgG and IgA antibody levels in both systemic and mucosal compartments were normal in TLR- and RLR-deficient mice. To further assess the susceptibility of these mice to influenza virus infection, protective efficacy was determined after primary or secondary lethal challenge. We found that MyD88(−/−) and MyD88(−/−) TRIF(−/−) mice were more susceptible to primary influenza virus infection than the B6 mice but were fully protected against homologous (H1N1) and heterosubtypic (H5N2) secondary infection when primed with a nonlethal dose of PR8 virus. Taken together, these results show that MyD88 signaling plays an important role for resisting primary influenza virus infection but is dispensable for protection against a secondary lethal challenge.",,"['Seo, Sang-Uk', 'Kwon, Hyung-Joon', 'Song, Joo-Hye', 'Byun, Young-Ho', 'Seong, Baik Lin', 'Kawai, Taro', 'Akira, Shizuo', 'Kweon, Mi-Na']",,,,
,PMC,For the record,http://dx.doi.org/10.1503/cmaj.109-3714,PMC2988561,,,,,,,,,
,PMC,"The lymphoid chemokine, CXCL13, is dispensable for the initial recruitment of B cells to the acutely inflamed central nervous system",http://dx.doi.org/10.1016/j.bbi.2010.10.002,PMC3135968,,,"Cases of progressive multifocal leukoencephalopathy can occur in patients treated with the B cell depleting anti-CD20 antibody, rituximab, highlighting the importance of B cell surveillance of the central nervous system (CNS). The lymphoid chemokine, CXCL13, is critical for B cell recruitment and functional organization of peripheral lymphoid tissues, and CXCL13 levels are often elevated in the inflamed CNS. To more directly investigate the role of CXCL13 in CNS B cell migration, its role in animal models of infectious and inflammatory demyelinating disease was examined. During acute alphavirus encephalitis where viral clearance depends on the local actions of anti-viral antibodies, CXCL13 levels and B cell numbers increased in brain tissue over time. Surprisingly, however, CXCL13-deficient animals showed normal CNS B cell recruitment, unaltered CNS virus replication and clearance, and intact peripheral anti-viral antibody responses. During experimental autoimmune encephalomyelitis (EAE), CNS levels of CXCL13 increased as symptoms emerged and equivalent numbers of B cells were identified among the CNS infiltrates of CXCL13-deficient mice compared to control animals. However, CXCL13-deficient mice did not sustain pathogenic anti-myelin T cell responses, consistent with their known propensity to develop more self-limited EAE. These data show that CXCL13 is dispensable for CNS B cell recruitment in both models. The disease course is unaffected by CXCL13 in a CNS infection paradigm that depends on a pathogen-specific B cell response, while it is heightened and prolonged by CXCL13 when myelin-specific CD4+ T cells drive CNS pathology. Thus, CXCL13 could be a therapeutic target in certain neuroinflammatory diseases, but not by blocking B cell recruitment to the CNS.",,"['Rainey-Barger, Emily K', 'Rumble, Julie M', 'Lalor, Stephen J.', 'Esen, Nilufer', 'Segal, Benjamin M', 'Irani, David N']",,,,
,PMC,NS-based Live Attenuated H1N1 Pandemic Vaccines Protect Mice and Ferrets,http://dx.doi.org/10.1016/j.vaccine.2010.08.106,PMC2991506,,,"Although vaccines against influenza A virus are the most effective method to combat infection, it is clear that their production needs to be accelerated and their efficacy improved. We generated live attenuated human influenza A vaccines (LAIVs) by rationally engineering mutations directly into the genome of a pandemic-H1N1 virus. Two LAIVs (NS1-73 and NS1-126) were based on the success of LAIVs for animal influenza A viruses. A third candidate (NSΔ5) is a unique NS-mutant that has never been used as a LAIV. The vaccine potential of each LAIV was determined through analysis of attenuation, interferon production, immunogenicity, and their ability to protect mice and ferrets. This study demonstrates that NSΔ5 is an ideal LAIV candidate, provides important information on the effects that different NS mutations have on the pandemic-H1N1 virus and shows that LAIVs can be engineered directly from the genomes of emerging/circulating influenza A viruses.",,"['Zhou, Bin', 'Li, Yan', 'Belser, Jessica A.', 'Pearce, Melissa B.', 'Schmolke, Mirco', 'Subba, Anju X.', 'Shi, Zhengli', 'Zaki, Sherif R.', 'Blau, Dianna M.', 'García-Sastre, Adolfo', 'Tumpey, Terrence M.', 'Wentworth, David E.']",,,,
,PMC,Identification of four novel DC-SIGN ligands on Mycobacterium bovis BCG,http://dx.doi.org/10.1007/s13238-010-0101-3,PMC4875224,,,"Dendritic-cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN; CD209) has an important role in mediating adherence of Mycobacteria species, including M. tuberculosis and M. bovis BCG to human dendritic cells and macrophages, in which these bacteria can survive intracellularly. DC-SIGN is a C-type lectin, and interactions with mycobacterial cells are believed to occur via mannosylated structures on the mycobacterial surface. Recent studies suggest more varied modes of binding to multiple mycobacterial ligands. Here we identify, by affinity chromatography and mass-spectrometry, four novel ligands of M. bovis BCG that bind to DC-SIGN. The novel ligands are chaperone protein DnaK, 60 kDa chaperonin-1 (Cpn60.1), glyceraldehyde-3 phosphate dehydrogenase (GAPDH) and lipoprotein lprG. Other published work strongly suggests that these are on the cell surface. Of these ligands, lprG appears to bind DC-SIGN via typical proteinglycan interactions, but DnaK and Cpn60.1 binding do not show evidence of carbohydrate-dependent interactions. LprG was also identified as a ligand for DC-SIGNR (L-SIGN; CD299) and the M. tuberculosis orthologue of lprG has been found previously to interact with human toll-like receptor 2. Collectively, these findings offer new targets for combating mycobacterial adhesion and within-host survival, and reinforce the role of DCSIGN as an important host ligand in mycobacterial infection.",,"['Carroll, Maria V.', 'Sim, Robert B.', 'Bigi, Fabiana', 'Jäkel, Anne', 'Antrobus, Robin', 'Mitchell, Daniel A.']",,,,
,PMC,"Development, Characterization, and Application of Monoclonal Antibodies against Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein",http://dx.doi.org/10.1128/CVI.00293-10,PMC3008203,,,"Five monoclonal antibodies (MAbs) against recombinant nucleocapsid protein (NP) of severe acute respiratory syndrome (SARS)-causing coronavirus (CoV) were developed by hybridoma technology. Epitope mapping by Western blotting showed that these anti-SARS-CoV NP MAbs bind to distinct domains of NP. These anti-SARS-CoV NP MAbs, with their high specificity, are potentially ideal candidates for developing early and sensitive diagnostic assays for SARS-CoV.",,"['Das, Dipankar', 'Kammila, Sriram', 'Suresh, Mavanur R.']",,,,
,PMC,Metagenomic Analysis of the Viromes of Three North American Bat Species: Viral Diversity among Different Bat Species That Share a Common Habitat,http://dx.doi.org/10.1128/JVI.01255-10,PMC3004358,,,"Effective prediction of future viral zoonoses requires an in-depth understanding of the heterologous viral population in key animal species that will likely serve as reservoir hosts or intermediates during the next viral epidemic. The importance of bats as natural hosts for several important viral zoonoses, including Ebola, Marburg, Nipah, Hendra, and rabies viruses and severe acute respiratory syndrome-coronavirus (SARS-CoV), has been established; however, the large viral population diversity (virome) of bats has been partially determined for only a few of the ∼1,200 bat species. To assess the virome of North American bats, we collected fecal, oral, urine, and tissue samples from individual bats captured at an abandoned railroad tunnel in Maryland that is cohabitated by 7 to 10 different bat species. Here, we present preliminary characterization of the virome of three common North American bat species, including big brown bats (Eptesicus fuscus), tricolored bats (Perimyotis subflavus), and little brown myotis (Myotis lucifugus). In samples derived from these bats, we identified viral sequences that were similar to at least three novel group 1 CoVs, large numbers of insect and plant virus sequences, and nearly full-length genomic sequences of two novel bacteriophages. These observations suggest that bats encounter and disseminate a large assortment of viruses capable of infecting many different animals, insects, and plants in nature.",,"['Donaldson, Eric F.', 'Haskew, Aimee N.', 'Gates, J. Edward', 'Huynh, Jeremy', 'Moore, Clea J.', 'Frieman, Matthew B.']",,,,
,PMC,Efficient Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by the Transmembrane Protease TMPRSS2,http://dx.doi.org/10.1128/JVI.01542-10,PMC3004351,,,"The distribution of the severe acute respiratory syndrome coronavirus (SARS-CoV) receptor, an angiotensin-converting enzyme 2 (ACE2), does not strictly correlate with SARS-CoV cell tropism in lungs; therefore, other cellular factors have been predicted to be required for activation of virus infection. In the present study, we identified transmembrane protease serine 2 (TMPRSS2), whose expression does correlate with SARS-CoV infection in the upper lobe of the lung. In Vero cells expressing TMPRSS2, large syncytia were induced by SARS-CoV infection. Further, the lysosome-tropic reagents failed to inhibit, whereas the heptad repeat peptide efficiently inhibited viral entry into cells, suggesting that TMPRSS2 affects the S protein at the cell surface and induces virus-plasma membrane fusion. On the other hand, production of virus in TMPRSS2-expressing cells did not result in S-protein cleavage or increased infectivity of the resulting virus. Thus, TMPRSS2 affects the entry of virus but not other phases of virus replication. We hypothesized that the spatial orientation of TMPRSS2 vis-a-vis S protein is a key mechanism underling this phenomenon. To test this, the TMPRSS2 and S proteins were expressed in cells labeled with fluorescent probes of different colors, and the cell-cell fusion between these cells was tested. Results indicate that TMPRSS2 needs to be expressed in the opposing (target) cell membrane to activate S protein rather than in the producer cell, as found for influenza A virus and metapneumoviruses. This is the first report of TMPRSS2 being required in the target cell for activation of a viral fusion protein but not for the S protein synthesized in and transported to the surface of cells. Our findings suggest that the TMPRSS2 expressed in lung tissues may be a determinant of viral tropism and pathogenicity at the initial site of SARS-CoV infection.",,"['Matsuyama, Shutoku', 'Nagata, Noriyo', 'Shirato, Kazuya', 'Kawase, Miyuki', 'Takeda, Makoto', 'Taguchi, Fumihiro']",,,,
,PMC,Evolved Variants of the Membrane Protein Can Partially Replace the Envelope Protein in Murine Coronavirus Assembly,http://dx.doi.org/10.1128/JVI.01850-10,PMC3004328,,,"The coronavirus small envelope (E) protein plays a crucial, but poorly defined, role in the assembly of virions. To investigate E protein function, we previously generated E gene point mutants of mouse hepatitis virus (MHV) that were defective in growth and assembled virions with anomalous morphologies. We subsequently constructed an E gene deletion (ΔE) mutant that was only minimally viable. The ΔE virus formed tiny plaques and reached optimal infectious titers many orders of magnitude below those of wild-type virus. We have now characterized highly aberrant viral transcription patterns that developed in some stocks of the ΔE mutant. Extensive analysis of three independent stocks revealed that, in each, a faster-growing virus harboring a genomic duplication had been selected. Remarkably, the net result of each duplication was the creation of a variant version of the membrane protein (M) gene that was situated upstream of the native copy of the M gene. Each different variant M gene encoded an expressed protein (M*) containing a truncated endodomain. Reconstruction of one variant M gene in a ΔE background showed that expression of the M* protein markedly enhanced the growth of the ΔE mutant and that the M* protein was incorporated into assembled virions. These findings suggest that M* proteins were repeatedly selected as surrogates for the E protein and that one role of E is to mediate interactions between transmembrane domains of M protein monomers. Our results provide a demonstration of the capability of coronaviruses to evolve new gene functions through recombination.",,"['Kuo, Lili', 'Masters, Paul S.']",,,,
,PMC,A framework for research ethics review during public emergencies,http://dx.doi.org/10.1503/cmaj.090976,PMC2950185,,,,,"['Tansey, Catherine M.', 'Herridge, Margaret S.', 'Heslegrave, Ronald J.', 'Lavery, James V.']",,,,
,PMC,Ubiquitination and deubiquitination of NP protein regulates influenza A virus RNA replication,http://dx.doi.org/10.1038/emboj.2010.250,PMC2989104,,,"Influenza A virus RNA replication requires an intricate regulatory network involving viral and cellular proteins. In this study, we examined the roles of cellular ubiquitinating/deubiquitinating enzymes (DUBs). We observed that downregulation of a cellular deubiquitinating enzyme USP11 resulted in enhanced virus production, suggesting that USP11 could inhibit influenza virus replication. Conversely, overexpression of USP11 specifically inhibited viral genomic RNA replication, and this inhibition required the deubiquitinase activity. Furthermore, we showed that USP11 interacted with PB2, PA, and NP of viral RNA replication complex, and that NP is a monoubiquitinated protein and can be deubiquitinated by USP11 in vivo. Finally, we identified K184 as the ubiquitination site on NP and this residue is crucial for virus RNA replication. We propose that ubiquitination/deubiquitination of NP can be manipulated for antiviral therapeutic purposes.",,"['Liao, Tsai-Ling', 'Wu, Chung-Yi', 'Su, Wen-Chi', 'Jeng, King-Song', 'Lai, Michael M C']",,,,
,PMC,Bispecific Adapter-Mediated Retargeting of a Receptor-Restricted HSV-1 Vector to CEA-Bearing Tumor Cells,http://dx.doi.org/10.1038/mt.2010.207,PMC3048173,,,"The safety and efficacy of viral therapies for solid tumors can be enhanced by redirecting the virus infection to tumor-specific cell-surface markers. Successful retargeting of herpes simplex virus type 1 (HSV-1) has been achieved using vectors that carry a modified envelope glycoprotein D (gD) engineered to interact directly with novel receptors. In addition, soluble bridging molecules (adapters) have been used to link gD indirectly to cell-specific receptors. Here, we describe the development of an adapter connecting gD to the common tumor antigen carcinoembryonic antigen (CEA). The adapter consisted of a CEA-specific single-chain antibody fused to the gD-binding region of the gD receptor, herpes virus entry mediator (HVEM). We used this adapter in combination with a vector that is detargeted for recognition of the widely expressed gD receptor nectin-1, but retains an intact binding region for the less common HVEM. We show that the adapter enabled infection of HSV-resistant Chinese hamster ovary (CHO) cells expressing ectopic CEA and nectin-1/CEA-bearing human gastric carcinoma cells that are resistant to the vector alone. We observed cell-to-cell spread following adapter-mediated infection in vitro and reduced tumor growth in vivo, indicating that this method of vector retargeting may provide a novel strategy for tumor-specific delivery of tumoricidal HSV.",,"['Baek, Hyunjung', 'Uchida, Hiroaki', 'Jun, Kyungok', 'Kim, Jae-Hong', 'Kuroki, Masahide', 'Cohen, Justus B', 'Glorioso, Joseph C', 'Kwon, Heechung']",,,,
,PMC,PNRC accumulates in the nucleolus by interaction with B23/nucleophosmin via its nucleolar localization sequence,http://dx.doi.org/10.1016/j.bbamcr.2010.09.017,PMC3085350,,,"PNRC (proline-rich nuclear receptor coregulatory protein) was primarily identified as a coactivator of nuclear receptors (NRs) by our laboratory, which enhances NR-mediated transcription by RNA polymerase II. Recent study has shown that PNRC also stimulates RNA polymerase III-dependent transcription through interaction with the subunit RPC39 of RNA polymerase III. Here, we report that PNRC accumulates in the nucleolus and its depletion by small interfering RNA (siRNA) impairs pre-rRNA transcription by RNA polymerase I. We identified the sequence at position 94–101 ((94)PKKRRKKK(101)) of PNRC as its nucleolar localization sequence (NoLS). Fusion of this sequence to GFP directed GFP to the nucleolus. Characterization of the NoLS revealed that the stretches of six successive basic residues are sufficient to function as a NoLS. Through co-immunoprecipitation assays, we demonstrated that the NoLS is necessary and sufficient to mediate the association of PNRC with B23/nucleophosmin. Moreover, B23 depletion by siRNA disrupted the accumulation of PNRC in the nucleolus. Together, our study indicates that PNRC is a novel nucleolar protein that might be involved in regulation of pre-rRNA synthesis, and it localizes to the nucleolus by interaction with B23 via its NoLS. Our study also suggests that the stretches of six successive basic residues (lysine and/or arginine) function as NoLS.",,"['Wang, Yuanzhong', 'Chen, Bin', 'Li, Yuping', 'Zhou, Dujin', 'Chen, Shiuan']",,,,
,PMC,The epidemiology of bovine respiratory disease: What is the evidence for predisposing factors?,,PMC2942046,,,"Bovine respiratory disease (BRD) is the most costly disease of beef cattle in North America. It is multi-factorial, with a variety of physical and physiological stressors combining to predispose cattle to pneumonia. However, efforts to discern which factors are most important have frequently failed to establish definitive answers. Calves are at highest risk shortly after transport. Risk factors include purchasing from sale barns and commingling. It is unclear whether or not these practices increase susceptibility, increase exposure, or are proxies for poor management. Lighter-weight calves appear to be at greater risk, although this has not been consistent. Persistent infection (PI) with bovine virus diarrhea virus increases BRD occurrence, but it is unclear if PI calves affect other cattle in the feedlot. The complexity of BRD has made it difficult to define involvement of individual factors. Stressors may play a role as “necessary but not sufficient” components, requiring additive effects to cause disease.",,"['Taylor, Jared D.', 'Fulton, Robert W.', 'Lehenbauer, Terry W.', 'Step, Douglas L.', 'Confer, Anthony W.']",,,,
,PMC,Poliovirus Replication Requires the N-terminus but not the Catalytic Sec7 Domain of ArfGEF GBF1,http://dx.doi.org/10.1111/j.1462-5822.2010.01482.x,PMC2945620,,,"Viruses are intracellular parasites whose reproduction relies on factors provided by the host. The cellular protein GBF1 is critical for poliovirus replication. Here we show that the contribution of GBF1 to virus replication is different from its known activities in uninfected cells. Normally GBF1 activates the Arf GTPases necessary for formation of COPI transport vesicles. GBF1 function is modulated by p115 and Rab1b. However, in polio-infected cells, p115 is degraded and neither p115 nor Rab1b knock-down affects virus replication. Poliovirus infection is very sensitive to BFA, an inhibitor of Arf activation by GBF1. BFA targets the catalytic Sec7 domain of GBF1. Nevertheless the BFA block of polio replication is rescued by expression of only the N-terminal region of GBF1 lacking the Sec7 domain. Replication of BFA-resistant poliovirus in the presence of BFA is uncoupled from Arf activation but is dependent on GBF1. Thus the function(s) of this protein essential for viral replication can be separated from those required for cellular metabolism.",,"['Belov, George A.', 'Kovtunovych, Gennadiy', 'Jackson, Catherine L.', 'Ehrenfeld, Ellie']",,,,
,PMC,CD23/FcεRII: molecular multi-tasking,http://dx.doi.org/10.1111/j.1365-2249.2010.04210.x,PMC2990925,,,"CD23 is the low-affinity receptor for immunoglobulin (Ig)E and plays important roles in the regulation of IgE responses. CD23 can be cleaved from cell surfaces to yield a range of soluble CD23 (sCD23) proteins that have pleiotropic cytokine-like activities. The regions of CD23 responsible for interaction with many of its known ligands, including IgE, CD21, major histocompatibility complex (MHC) class II and integrins, have been identified and help to explain the structure–function relationships within the CD23 protein. Translational studies of CD23 underline its credibility as a target for therapeutic intervention strategies and illustrate its involvement in mediating therapeutic effects of antibodies directed at other targets.",,"['Acharya, M', 'Borland, G', 'Edkins, A L', 'MacLellan, L M', 'Matheson, J', 'Ozanne, B W', 'Cushley, W']",,,,
,PMC,Thoracic Radiography as a Refinement Methodology for the Study of H1N1 Influenza in Cynomologus Macaques (Macaca fascicularis),,PMC2958208,,,"Recent advances in the technology associated with digital radiography have created new opportunities for biomedical research applications. Here we evaluated the use of thoracic radiography as a noninvasive refinement methodology for the cynomologus macaque (Macaca fascicularis) model of H1N1 infection. Thoracic radiographic evaluations of macaques infected with any of 3 strains of emerging H1N1 swine-associated influenza virus isolated during the recent pandemic were compared with those of macaques infected with the currently circulating Kawasaki strain of H1N1 influenza. Ventrodorsal, right, and left lateral thoracic radiographs were obtained at days 0, 1, 6, 8, 11, and 14 after infection. A board-certified veterinary radiologist who was blinded to the study design evaluated the images. Numeric scores of extent and severity of lung involvement assigned to each radiograph were compared and demonstrated a significant and substantial difference among groups. The radiographic evaluation allowed for noninvasive assessment of lung involvement, disease onset, progression, and resolution of radiographic changes associated with H1N1 influenza infection.",,"['Brining, Douglas L', 'Mattoon, John S', 'Kercher, Lisa', 'LaCasse, Rachael A', 'Safronetz, David', 'Feldmann, Heinz', 'Parnell, Michael J']",,,,
,PMC,Production of adenovirus vectors and their use as a delivery system for influenza vaccines,http://dx.doi.org/10.1517/14712598.2010.519332,PMC2951029,,,"IMPORTANCE OF THE FIELD: With the emergence of highly pathogenic avian influenza H5N1 viruses that have crossed species barriers and are responsible for lethal infections in humans in many countries, there is an urgent need for the development of effective vaccines which can be produced in large quantities at a short notice and confer broad protection against these H5N1 variants. In order to meet the potential global vaccine demand in a pandemic scenario, new vaccine-production strategies must be explored in addition to the currently used egg-based technology for seasonal influenza. AREAS COVERED IN THIS REVIEW: Adenovirus (Ad) based influenza vaccines represent an attractive alternative/supplement to the currently licensed egg-based influenza vaccines. Ad-based vaccines are relatively inexpensive to manufacture, and their production process does not require either chicken eggs or labor intensive and time-consuming processes necessitating enhanced biosafety facilities. Most importantly, in a pandemic situation, this vaccine strategy could offer a stockpiling option to reduce the response time before a strain-matched vaccine could be developed. WHAT THE READER WILL GAIN: This review discusses Ad-vector technology and the current progress in the development of Ad-based influenza vaccines. TAKE HOME MESSAGE: Ad vector-based influenza vaccines for pandemic preparedness are under development to meet the global vaccine demand.",,"['Vemula, Sai V.', 'Mittal, Suresh K.']",,,,
,PMC,Involvement of p300 in constitutive and HIV-1 Tat-activated expression of glial fibrillary acidic protein in astrocytes,http://dx.doi.org/10.1002/glia.21038,PMC2919602,,,"HIV-1 Tat protein is an important pathogenic factor in HIV-1-associated neurological diseases. One hallmark of HIV-1 infection of the central nervous system (CNS) is astrocytosis, which is characterized by elevated GFAP expression in astrocytes. We have shown that Tat activates GFAP expression in astrocytes (Zhou, et al., Mol. Cell. Neurosci. 27:296, 2004) and that GFAP is an important regulator of Tat neurotoxicity (Zou, et. al., Am. J. Pathol. 171:1293, 2007). However, the underlying mechanisms for Tat-mediated GFAP up-regulation are not understood. In the current study, we reported concurrent up-regulation of adenovirus E1a-associated 300 kDa protein p300 and GFAP in Tat-expressing human astroytoma cells and primary astrocytes. We showed that p300 was indeed induced by Tat expression and HIV-1 infection and that the induction occurred at the transcriptional level through the cis-acting elements of early growth response 1 (Egr-1) within its promoter. Using siRNA, we further showed that p300 regulated both constitutive and Tat-mediated GFAP expression. Moreover, we showed that ectopic expression of p300 potentiated Tat transactivation activity and increased proliferation of HIV-1-infected astrocytes, but had little effect on HIV-1 replication in these cells. Taken together, these results demonstrate for the first time that Tat is a positive regulator of p300 expression, which in turn regulates GFAP expression, and suggest that the Tat-Egr-1-p300-GFAP axis likely contributes to Tat neurotoxicity and predisposes astrocytes to be an HIV-1 sanctuary in the CNS.",,"['Zou, Wei', 'Wang, Zhenyuan', 'Liu, Ying', 'Fan, Yan', 'Zhou, Betty Y.', 'Yang, X. Frank', 'He, Johnny J.']",,,,
,PMC,Sphaeranthus indicus Linn.: A phytopharmacological review,http://dx.doi.org/10.4103/0974-7788.76790,PMC3059449,21455454,CC BY-NC-SA,"Sphaeranthus indicus Linn. (Asteraceae) is widely used in Ayurvedic system of medicine to treat vitiated conditions of epilepsy, mental illness, hemicrania, jaundice, hepatopathy, diabetes, leprosy, fever, pectoralgia, cough, gastropathy, hernia, hemorrhoids, helminthiasis, dyspepsia and skin diseases. There are reports providing scientific evidences for hypotensive, anxiolytic, neuroleptic, hypolipidemic, immunomodulatory, antioxidant, anti-inflammatory, bronchodialatory, antihyperglycemic and hepatoprotective activities of this plant. A wide range of phytochemical constituents have been isolated from this plant including sesquiterpene lactones, eudesmenolides, flavanoids and essential oil. A comprehensive account of the morphology, phytochemical constituents, ethnobotanical uses and pharmacological activities reported are included in this review for exploring the immense medicinal potential of this plant.",2010 Oct-Dec,"['Galani, Varsha J.', 'Patel, B. G.', 'Rana, D. G.']",Int J Ayurveda Res,,,
,PMC,Review Part 2: Human Herpesvirus-6 in Central Nervous System Diseases,http://dx.doi.org/10.1002/jmv.21861,PMC4758195,,,,,"['Yao, Karen', 'Crawford, John R.', 'Komaroff, Anthony L.', 'Ablashi, Dharam V.', 'Jacobson, Steven']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.01670-10,PMC2937752,,,,,,,,,
,PMC,Development of an optimized RNA-based murine norovirus reverse genetics system,http://dx.doi.org/10.1016/j.jviromet.2010.07.006,PMC2989447,20637238,CC BY,"Murine norovirus (MNV), identified in 2003, is the only norovirus which replicates efficiently in tissue culture and as a result has been used extensively as a model for human noroviruses, a major cause of acute gastroenteritis. The current report describes the generation of a new approach to reverse genetics recovery of genetically defined MNV that relies on the transfection of in vitro transcribed capped RNA directly into cells. The use of the recently developed ScriptCap post-transcriptional enzymatic capping system, followed by optimized Neon mediated electroporation of the highly permissive RAW 264.7 cells, resulted in the rapid and robust recovery of infectious MNV. Transfection of cells capable of supporting virus replication but not permissive to virus infection, namely human or hamster kidney cells, also resulted in robust recovery of infectious virus without subsequent amplification by multiple rounds of re-infection. This latter system may provide a reproducible method to measure the specific infectivity of mutant norovirus RNA allowing the accurate quantitation of the effect of mutations on norovirus replication.",2010 Oct,"['Yunus, Muhammad Amir', 'Chung, Liliane Man Wah', 'Chaudhry, Yasmin', 'Bailey, Dalan', 'Goodfellow, Ian']",J Virol Methods,,,
,PMC,Development of a large-scale isolation chamber system for the safe and humane care of medium-sized laboratory animals harboring infectious diseases,http://dx.doi.org/10.1631/jzus.B1000111,PMC2950238,,,"The close phylogenetic relationship between humans and non-human primates makes non-human primates an irreplaceable model for the study of human infectious diseases. In this study, we describe the development of a large-scale automatic multi-functional isolation chamber for use with medium-sized laboratory animals carrying infectious diseases. The isolation chamber, including the transfer chain, disinfection chain, negative air pressure isolation system, animal welfare system, and the automated system, is designed to meet all biological safety standards. To create an internal chamber environment that is completely isolated from the exterior, variable frequency drive blowers are used in the air-intake and air-exhaust system, precisely controlling the filtered air flow and providing an air-barrier protection. A double door transfer port is used to transfer material between the interior of the isolation chamber and the outside. A peracetic acid sterilizer and its associated pipeline allow for complete disinfection of the isolation chamber. All of the isolation chamber parameters can be automatically controlled by a programmable computerized menu, allowing for work with different animals in different-sized cages depending on the research project. The large-scale multi-functional isolation chamber provides a useful and safe system for working with infectious medium-sized laboratory animals in high-level bio-safety laboratories.",,"['Pan, Xin', 'Qi, Jian-cheng', 'Long, Ming', 'Liang, Hao', 'Chen, Xiao', 'Li, Han', 'Li, Guang-bo', 'Zheng, Hao']",,,,
,PMC,Intrinsic antibody-dependent enhancement of microbial infection in macrophages: disease regulation by immune complexes,http://dx.doi.org/10.1016/S1473-3099(10)70166-3,PMC3057165,,,"A wide range of microorganisms can replicate in macrophages, and cell entry of these pathogens via non-neutralising IgG antibody complexes can result in increased intracellular infection through idiosyncratic Fcγ-receptor signalling. The activation of Fcγ receptors usually leads to phagocytosis. Paradoxically, the ligation of monocyte or macrophage Fcγ receptors by IgG immune complexes, rather than aiding host defences, can suppress innate immunity, increase production of interleukin 10, and bias T-helper-1 (Th1) responses to Th2 responses, leading to increased infectious output by infected cells. This intrinsic antibody-dependent enhancement (ADE) of infection modulates the severity of diseases as disparate as dengue haemorrhagic fever and leishmaniasis. Intrinsic ADE is distinct from extrinsic ADE, whereby complexes of infectious agents with non-neutralising antibodies lead to an increased number of infected cells. Intrinsic ADE might be involved in many protozoan, bacterial, and viral infections. We review insights into intracellular mechanisms and implications of enhanced pathogenesis after ligation of macrophage Fcγ receptors by infectious immune complexes.",,"['Halstead, Scott B', 'Mahalingam, Prof Suresh', 'Marovich, Mary A', 'Ubol, Sukathida', 'Mosser, Prof David M']",,,,
,PMC,The SCHOOL of nature: IV. Learning from viruses,http://dx.doi.org/10.4161/self.1.4.13279,PMC3062383,,,"During the co-evolution of viruses and their hosts, the latter have equipped themselves with an elaborate immune system to defend themselves from the invading viruses. In order to establish a successful infection, replicate and persist in the host, viruses have evolved numerous strategies to counter and evade host antiviral immune responses as well as exploit them for productive viral replication. These strategies include those that modulate signaling mediated by cell surface receptors. Despite tremendous advancement in recent years, the exact molecular mechanisms underlying these critical points in viral pathogenesis remain unknown. In this work, based on a novel platform of receptor signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) platform, I suggest specific mechanisms used by different viruses such as human immunodeficiency virus (HIV), cytomegalovirus (CMV), severe acute respiratory syndrome coronavirus, human herpesvirus 6 and others, to modulate receptor signaling. I also use the example of HIV and CMV to illustrate how two unrelated enveloped viruses use a similar SCHOOL mechanism to modulate the host immune response mediated by two functionally different receptors: T cell antigen receptor and natural killer cell receptor, NKp30. This suggests that it is very likely that similar general mechanisms can be or are used by other viral and possibly non-viral pathogens. Learning from viruses how to target cell surface receptors not only helps us understand viral strategies to escape from the host immune surveillance, but also provides novel avenues in rational drug design and the development of new therapies for immune disorders.",,"Sigalov, Alexander B",,,,
,PMC,Porcine Reproductive and Respiratory Syndrome Virus–Induced Immunosuppression Exacerbates the Inflammatory Response to Porcine Respiratory Coronavirus in Pigs,http://dx.doi.org/10.1089/vim.2010.0051,PMC2967820,,,"We performed a comprehensive analysis of innate and adaptive immune responses in dual-virus infected pigs to understand whether a pre-existing immunomodulatory respiratory viral infection affects the overall immunity to a subsequent porcine respiratory coronavirus (PRCV) infection in pigs. Pigs were either mock-infected or infected with porcine reproductive and respiratory syndrome virus (PRRSV), a virus known to cause immunosuppressive respiratory disease, and then pigs were co-infected with PRCV, which normally causes subclinical respiratory infection. We collected samples for six independent experiments from 178 pigs that were also used for pathological studies. We detected a significant reduction in innate NK-cell-mediated cytotoxic function in PRRSV-infected pigs, which was synergistically further decreased in pigs co-infected with PRCV. Subsequently, in association with clinical signs we observed elevated levels of proinflammatory (IL-6), Th-1 (IL-12), and regulatory (IL-10 and TGF-β) cytokines. Increased frequencies of CD4CD8 double-positive T lymphocytes and myeloid cells, in addition to the elevated Th-1 and proinflammatory cytokines in dual-infected pigs, contributed to the severity of lung disease in pigs. The results of our study clarify how each virus modulates the host innate and adaptive immune responses, leading to inflammatory reactions and lung pathology. Thus measurements of cytokines and frequencies of immune cells may serve as indicators of the progression of respiratory viral co-infections, and provide more definitive approaches for treatment.",,"['Renukaradhya, Gourapura J.', 'Alekseev, Konstantin', 'Jung, Kwonil', 'Fang, Ying', 'Saif, Linda J.']",,,,
,PMC,Immunogenicity and Protective Efficacy in Mice and Hamsters of a β-Propiolactone Inactivated Whole Virus SARS-CoV Vaccine,http://dx.doi.org/10.1089/vim.2010.0028,PMC2967819,,,"The immunogenicity and efficacy of β-propiolactone (BPL) inactivated whole virion SARS-CoV (WI-SARS) vaccine was evaluated in BALB/c mice and golden Syrian hamsters. The vaccine preparation was tested with or without adjuvants. Adjuvant Systems AS01(B) and AS03(A) were selected and tested for their capacity to elicit high humoral and cellular immune responses to WI-SARS vaccine. We evaluated the effect of vaccine dose and each adjuvant on immunogenicity and efficacy in mice, and the effect of vaccine dose with or without the AS01(B) adjuvant on the immunogenicity and efficacy in hamsters. Efficacy was evaluated by challenge with wild-type virus at early and late time points (4 and 18 wk post-vaccination). A single dose of vaccine with or without adjuvant was poorly immunogenic in mice; a second dose resulted in a significant boost in antibody levels, even in the absence of adjuvant. The use of adjuvants resulted in higher antibody titers, with the AS01(B)-adjuvanted vaccine being slightly more immunogenic than the AS03(A)-adjuvanted vaccine. Two doses of WI-SARS with and without Adjuvant Systems were highly efficacious in mice. In hamsters, two doses of WI-SARS with and without AS01(B) were immunogenic, and two doses of 2 μg of WI-SARS with and without the adjuvant provided complete protection from early challenge. Although antibody titers had declined in all groups of vaccinated hamsters 18 wk after the second dose, the vaccinated hamsters were still partially protected from wild-type virus challenge. Vaccine with adjuvant provided better protection than non-adjuvanted WI-SARS vaccine at this later time point. Enhanced disease was not observed in the lungs or liver of hamsters following SARS-CoV challenge, regardless of the level of serum neutralizing antibodies.",,"['Roberts, Anjeanette', 'Lamirande, Elaine W.', 'Vogel, Leatrice', 'Baras, Benoît', 'Goossens, Geneviève', 'Knott, Isabelle', 'Chen, Jun', 'Ward, Jerrold M.', 'Vassilev, Ventzislav', 'Subbarao, Kanta']",,,,
,PMC,Engaging hospitals to meet tuberculosis control targets in China: using the Internet as a tool to put policy into practice,http://dx.doi.org/10.2471/BLT.09.071753,PMC2995179,,,"Tuberculosis (TB) services in China are provided through a large network of TB dispensaries. Even though hospitals are not as well placed to follow recommended standards of TB care, a significant proportion of people with TB symptoms seek care from hospitals. In spite of having a policy and mandate in place, the Ministry of Health had little success in encouraging hospitals to refer suspected TB cases to dispensaries. Following the epidemic of severe acute respiratory syndrome in 2003, the government set up a nationwide Internet-based communicable diseases reporting system. This achieved productive collaboration between hospitals and TB dispensaries. From 2004 to 2007, the percentage of TB suspects and patients needing referral from hospitals who arrived in TB dispensaries increased substantially from 58.7% to 77.8% and the contribution of hospitals to diagnosing sputum smear-positive TB cases doubled from 16.3% to 32.9%. Using the Internet-based reporting system, hospitals in China contributed to finding about one third of all sputum smear-positive TB cases and helped meet the global TB control target of detecting 70% of such cases. Based on the data available from routine surveillance facilitated by this Internet-based system, this paper details the process and outcomes of strengthening collaboration between hospitals and TB dispensaries using the Internet as a tool and its potential application to other country settings.",,"['Wang, Lixia', 'Liu, Xiaoqiu', 'Huang, Fei', 'Hennig, Cornelia', 'Uplekar, Mukund', 'Jiang, Shiwen']",,,,
,PMC,Hepatitis B Virus (HBV) Subgenotypes C2 and B2 Differ in Lamivudine- and Adefovir-Resistance-Associated Mutational Patterns in HBV-Infected Chinese Patients,http://dx.doi.org/10.1128/JCM.01518-10,PMC3008443,,,"We aimed to study the prevalence and clinical implications of hepatitis B virus (HBV) subgenotypes in Chinese patients. A total of 4,300 patients, mainly from northern China, were enrolled, including 182 patients with acute hepatitis B and 4,118 patients with chronic HBV infection who had been exposed to nucleoside or nucleotide analogs. HBV genotypes/subgenotypes were determined by direct sequencing of the HBV S/Pol region. The prevalence rates were 0.40% for HBV/B1, 14.30% for HBV/B2, 0.25% for HBV/B3, 0.35% for HBV/B4, 1.05% for HBV/C1, 81.72% for HBV/C2, 0.93% for HBV/C3, 0.16% for HBV/C4, and 0.84% for HBV/D. In chronic HBV infection, patients with HBV/B2 were younger and had lower ΗBeAg positive rates than patients with HBV/C2. The incidence of lamivudine-resistant mutations was significantly higher in HBV/C2 compared to HBV/B2 (27.9% versus 19.8%; P < 0.01), and the significant difference was observed only for rtM204I and not rtM204V. In addition, compensatory mutations were more frequently detected in HBV/C2. The incidence of adefovir-resistant mutations was similar between the two subsets, but HBV/C2 inclined to show rtA181V (3.6% for C2 versus 0.9% for B2; P < 0.01), while HBV/B2 inclined to show rtN236T (4.5% for versus 2.5% for C2; P < 0.01). The ratios of HBV/B2 to HBV/C2 infection were 1.7 (110/65), 5.7 (2,653/463), 7.5 (520/69), 8.0 (48/6), and 15.3 (183/12) for acute hepatitis B, chronic hepatitis B, liver cirrhosis, acute-on-chronic liver failure, and hepatocellular carcinoma, respectively. In conclusion, HBV/C2 and HBV/B2, two prevalent subgenotypes, differ in lamivudine- and adefovir-resistance-associated mutational patterns. HBV/C2-infected patients are more likely to have disease progression than HBV/B2-infected ones.",,"['Li, Xiaodong', 'Wang, Lin', 'Zhong, Yanwei', 'Wong, Vincent Wai-Sun', 'Xu, Zhihui', 'Liu, Yan', 'Li, Qinghong', 'Xin, Shaojie', 'Zhao, Jingmin', 'Xu, Dongping']",,,,
,PMC,How Innate Immune Mechanisms Contribute to Antibody-Enhanced Viral Infections,http://dx.doi.org/10.1128/CVI.00316-10,PMC3008185,,,"Preexisting antibodies may enhance viral infections. In dengue, nonneutralizing antibodies raised by natural infection with one of four dengue viruses (DENVs) may enhance infection with a different virus by a process we term “intrinsic antibody-dependent enhancement” (iADE). In addition, nonprotective antibodies raised by formalin-inactivated respiratory syncytial virus (RSV) and measles virus vaccines have led to enhanced disease during breakthrough infections. Infections under iADE conditions not only facilitate the process of viral entry into monocytes and macrophages but also modify innate and adaptive intracellular antiviral mechanisms, suppressing type 1 interferon (IFN) production and resulting in enhanced DENV replication. The suppression observed in vitro has been documented in patients with severe (dengue hemorrhagic fever [DHF]) but not in patient with mild (dengue fever [DF]) secondary dengue virus infections. Important veterinary viral infections also may exhibit iADE. It is thought that use of formalin deconforms viral epitopes of RSV, resulting in poor Toll-like receptor (TLR) stimulation; suboptimal maturation of dendritic cells with reduced production of activation factors CD40, CD80, and CD86; decreased germinal center formation in lymph nodes; and the production of nonprotective antibodies. These antibodies fail to neutralize RSV, allowing replication with secondary stimulation of RSV-primed Th2 cells producing more low-avidity antibody, resulting in immune complexes deposited into affected tissue. However, when formalin-inactivated RSV was administered with a TLR agonist to mice, they were protected against wild-type virus challenge. Safe and effective vaccines against RSV/measles virus and dengue virus may benefit from a better understanding of how innate immune responses can promote production of protective antibodies.",,"['Ubol, Sukathida', 'Halstead, Scott B.']",,,,
,PMC,Enhanced Antiviral T Cell Function in the Absence of B7-H1 is Insufficient to Prevent Persistence but Exacerbates Axonal Bystander Damage during Viral Encephalomyelitis(),http://dx.doi.org/10.4049/jimmunol.1001984,PMC3159959,,,"The T cell inhibitory ligand B7-H1 hinders T cell-mediated virus control, but also ameliorates clinical disease during autoimmune and virus induced CNS disease. In mice infected with glia-tropic demyelinating coronavirus, B7-H1 expression on oligodendroglia delays virus control, but also dampens clinical disease. To define the mechanisms by which B7-H1 alters pathogenic outcome, virus infected B7-H1 deficient (B7-H1(-/-)) mice were analyzed for altered peripheral and CNS immune responses. B7-H1 deficiency did not affect peripheral T or B cell activation, nor alter the magnitude or composition of CNS infiltrating cells. However, higher levels of IFN-γ mRNA in CNS infiltrating virus-specific CD8 T cells as well as CD4 T cells contributed to elevated IFN-γ protein in the B7-H1(-/-) CNS. Increased effector function at the single cell level was also evident by elevated granzyme B expression specifically in virus-specific CNS CD8 T cells. Although enhanced T cell activity accelerated virus control, 50% of mice succumbed to infection. Despite enhanced clinical recovery, surviving B7-H1(-/-) mice still harbored persisting viral mRNA, albeit at reduced levels compared to wild-type mice. B7-H1(-/-)mice exhibited extensive loss of axonal integrity although demyelination, a hallmark of virus induced tissue damage, was not increased. The results suggest that B7-H1 hinders viral control in B7-H1 expressing glia cells, but does not mediate resistance to CD8 T cell-mediated cytolysis. These data are the first to demonstrate that B7-H1-mediated protection from viral induced immune pathology associated with encephalomyelitis resides in limiting T cell-mediated axonal bystander damage, rather than direct elimination of infected myelinating cells.",,"['Phares, Timothy W.', 'Stohlman, Stephen A.', 'Hinton, David R.', 'Atkinson, Roscoe', 'Bergmann, Cornelia C.']",,,,
,PMC,New human rhinovirus species and their significance in asthma exacerbation and airway remodeling: Immunology and Allergy Clinics of North America Asthma and Infectious Disease,http://dx.doi.org/10.1016/j.iac.2010.08.007,PMC2967460,,,,,"Miller, E. Kathryn",,,,
,PMC,A Flow Cytometry-Based Strategy to Identify and Express IgM from VH1-69(+) Clonal Peripheral B Cells,http://dx.doi.org/10.1016/j.jim.2010.09.022,PMC3003765,,,"Pathologic rheumatoid factor (RF) levels are hallmarks of several human diseases. Production of monoclonal RF in vitro is essential for studies of the antigenic specificities of RF, as well as for a dissection of the mechanisms of aberrant RF(+) B cell activation. We have expanded upon previous methods to develop a flow cytometry-based method to efficiently clone monoclonal antibodies (mAbs) from humans with expansions of RF-like, immunoglobulin heavy chain variable region (IgVH) 1-69 gene segment-containing B cells. The cloned variable regions are expressed as IgM and produced during culture at concentrations between 5–20 μg/ml. Using this system, we show that clonal Igs from patients with HCV-related mixed cryoglobulinemia, when expressed as IgM, have RF activity. We anticipate that this system will be useful for the cloning and expression of mAbs partially encoded by VH1-69 and for determination of the reactivity patterns of polyspecific, low-affinity IgMs of human pathogenic importance.",,"['Charles, Edgar D.', 'Orloff, Michael I. M.', 'Dustin, Lynn B.']",,,,
,PMC,Functional Protein Microarray Technology,http://dx.doi.org/10.1002/wsbm.118,PMC3044218,,,"Functional protein microarrays are emerging as a promising new tool for large-scale and high-throughput studies. In this article, we will review their applications in basic proteomics research, where various types of assays have been developed to probe binding activities to other biomolecules, such as proteins, DNA, RNA, small molecules, and glycans. We will also report recent progress of using functional protein microarrays in profiling protein posttranslational modifications, including phosphorylation, ubiquitylation, acetylation, and nitrosylation. Finally, we will discuss potential of functional protein microarrays in biomarker identification and clinical diagnostics. We strongly believe that functional protein microarrays will soon become an indispensible and invaluable tool in proteomics research and systems biology.",,"['Hu, Shaohui', 'Xie, Zhi', 'Qian, Jiang', 'Blackshaw, Seth', 'Zhu, Heng']",,,,
,PMC,Membrane Potential Depolarization as a Triggering Mechanism for Vpu-Mediated HIV-1 Release,http://dx.doi.org/10.1016/j.bpj.2010.07.027,PMC2941015,,,"Vpu, a component unique to HIV-1, greatly enhances the efficiency of viral particle release by unclear mechanisms. This Vpu function is intrinsically linked to its channel-like structure, which enables it to interfere with homologous transmembrane structures in infected cells. Because Vpu interacts destructively with host background K(+) channels that set the cell resting potential, we hypothesized that Vpu might trigger viral release by destabilizing the electric field across a budding membrane. Here, we found that the efficiency of Vpu-mediated viral release is inversely correlated with membrane potential polarization. By inhibiting the background K(+) currents, Vpu dissipates the voltage constraint on viral particle discharge. As a proof of concept, we show that HIV-1 release can be accelerated by externally imposed depolarization alone. Our findings identify the trigger of Vpu-mediated release as a manifestation of the general principle of depolarization-stimulated exocytosis.",,"['Hsu, Kate', 'Han, Jin', 'Shinlapawittayatorn, Krekwit', 'Deschenes, Isabelle', 'Marbán, Eduardo']",,,,
,PMC,Characterization of Pneumonia Due to Streptococcus equi subsp. zooepidemicus in Dogs,http://dx.doi.org/10.1128/CVI.00188-10,PMC2976090,,,"Streptococcus equi subsp. zooepidemicus has been linked to cases of acute fatal pneumonia in dogs in several countries. Outbreaks can occur in kenneled dog populations and result in significant levels of morbidity and mortality. This highly contagious disease is characterized by the sudden onset of clinical signs, including pyrexia, dyspnea, and hemorrhagic nasal discharge. The pathogenesis of S. equi subsp. zooepidemicus infection in dogs is poorly understood. This study systematically characterized the histopathological changes in the lungs of 39 dogs from a large rehoming shelter in London, United Kingdom; the dogs were infected with S. equi subsp. zooepidemicus. An objective scoring system demonstrated that S. equi subsp. zooepidemicus caused pneumonia in 26/39 (66.7%) dogs, and most of these dogs (17/26 [65.4%]) were classified as severe fibrino-suppurative, necrotizing, and hemorrhagic. Three recently described superantigen genes (szeF, szeN, and szeP) were detected by PCR in 17/47 (36.2%) of the S. equi subsp. zooepidemicus isolates; however, there was no association between the presence of these genes and the histopathological score. The lungs of S. equi subsp. zooepidemicus-infected dogs with severe respiratory signs and lung pathology did however have significantly higher mRNA levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 8 (IL-8) than in uninfected controls, suggesting a role for an exuberant host immune response in the pathogenesis of this disease.",,"['Priestnall, Simon L.', 'Erles, Kerstin', 'Brooks, Harriet W.', 'Cardwell, Jacqueline M.', 'Waller, Andrew S.', 'Paillot, Romain', 'Robinson, Carl', 'Darby, Alistair C.', 'Holden, Matthew T. G.', 'Schöniger, Sandra']",,,,
,PMC,The role of respiratory virus infections in childhood asthma inception,http://dx.doi.org/10.1016/j.iac.2010.08.004,PMC2966844,,,,,"['Jackson, Daniel J.', 'Lemanske, Robert F.']",,,,
,PMC,"Nested PCR-Linked Capillary Electrophoresis and Single-Strand Conformation Polymorphisms for Detection of Macrolide-Resistant Mycoplasma pneumoniae in Beijing, China",http://dx.doi.org/10.1128/JCM.00400-10,PMC3008430,,,"Mycoplasma pneumoniae is usually susceptible to macrolides, but macrolide-resistant strains have been found frequently in recent years. Mutations in domain V of the 23S rRNA gene of M. pneumoniae interfere with the binding of macrolides to rRNA and mediate macrolide resistance. In this study, we developed a rapid and inexpensive method that combines nested PCR (nPCR), single-strand conformation polymorphisms (SSCPs), and capillary electrophoresis (CE) to detect macrolide-resistant mutants directly from throat swabs. nPCR was used to specifically amplify M. pneumoniae 23S rRNA gene fragments containing mutations, and amplicons were analyzed by CE-SSCP for macrolide resistance mutations, with results confirmed by sequencing. From January to December 2009, 665 throat swabs were collected in Beijing, China, yielding 110 samples that tested positive for M. pneumoniae by nPCR and serological testing. We randomly selected 64 positive throat swabs for CE-SSCP analysis. The A2063G mutation was found in 57 samples, and a coexisting T2611C mutation was identified in 1 sample. An A2063T mutation was identified in 1 sample. The total mutation rate was 91%. All mutant samples identified by nPCR-CE-SSCP were sequenced. The nPCR-CE-SSCP method could identify macrolide-resistant mutants directly from clinical samples. This is the first report of an nPCR-CE-SSCP assay for the detection of dominant mutations that confer macrolide resistance on M. pneumoniae. This approach would allow clinicians to choose appropriate therapy rapidly and could be used as a screening method for genetic mutations related to antibiotic resistance.",,"['Lin, Changying', 'Li, Shaoli', 'Sun, Hongmei', 'Zhao, Hanqing', 'Feng, Yanling', 'Cao, Ling', 'Yuan, Yi', 'Zhang, Ting']",,,,
,PMC,Influenza A Virus Replication Induces Cell Cycle Arrest in G(0)/G(1) Phase,http://dx.doi.org/10.1128/JVI.01216-10,PMC3004346,,,"Many viruses interact with the host cell division cycle to favor their own growth. In this study, we examined the ability of influenza A virus to manipulate cell cycle progression. Our results show that influenza A virus A/WSN/33 (H1N1) replication results in G(0)/G(1)-phase accumulation of infected cells and that this accumulation is caused by the prevention of cell cycle entry from G(0)/G(1) phase into S phase. Consistent with the G(0)/G(1)-phase accumulation, the amount of hyperphosphorylated retinoblastoma protein, a necessary active form for cell cycle progression through late G(1) into S phase, decreased after infection with A/WSN/33 (H1N1) virus. In addition, other key molecules in the regulation of the cell cycle, such as p21, cyclin E, and cyclin D1, were also changed and showed a pattern of G(0)/G(1)-phase cell cycle arrest. It is interesting that increased viral protein expression and progeny virus production in cells synchronized in the G(0)/G(1) phase were observed compared to those in either unsynchronized cells or cells synchronized in the G(2)/M phase. G(0)/G(1)-phase cell cycle arrest is likely a common strategy, since the effect was also observed in other strains, such as H3N2, H9N2, PR8 H1N1, and pandemic swine H1N1 viruses. These findings, in all, suggest that influenza A virus may provide favorable conditions for viral protein accumulation and virus production by inducing a G(0)/G(1)-phase cell cycle arrest in infected cells.",,"['He, Yuan', 'Xu, Ke', 'Keiner, Bjoern', 'Zhou, Jianfang', 'Czudai, Volker', 'Li, Tianxian', 'Chen, Ze', 'Liu, Jinhua', 'Klenk, Hans-Dieter', 'Shu, Yue Long', 'Sun, Bing']",,,,
,PMC,Proteasome Inhibition In Vivo Promotes Survival in a Lethal Murine Model of Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1128/JVI.01219-10,PMC2976395,,,"Ubiquitination is a critical regulator of the host immune response to viral infection, and many viruses, including coronaviruses, encode proteins that target the ubiquitination system. To explore the link between coronavirus infection and the ubiquitin system, we asked whether protein degradation by the 26S proteasome plays a role in severe coronavirus infections using a murine model of SARS-like pneumonitis induced by murine hepatitis virus strain 1 (MHV-1). In vitro, the pretreatment of peritoneal macrophages with inhibitors of the proteasome (pyrrolidine dithiocarbamate [PDTC], MG132, and PS-341) markedly inhibited MHV-1 replication at an early step in its replication cycle, as evidenced by inhibition of viral RNA production. Proteasome inhibition also blocked viral cytotoxicity in macrophages, as well as the induction of inflammatory mediators such as IP-10, gamma interferon (IFN-γ), and monocyte chemoattractant protein 1 (MCP-1). In vivo, intranasal inoculation of MHV-1 results in a lethal pneumonitis in A/J mice. Treatment of A/J mice with the proteasome inhibitor PDTC, MG132, or PS-341 led to 40% survival (P < 0.01), with a concomitant improvement of lung histology, reduced pulmonary viral replication, decreased pulmonary STAT phosphorylation, and reduced pulmonary inflammatory cytokine expression. These data demonstrate that inhibition of the cellular proteasome attenuates pneumonitis and cytokine gene expression in vivo by reducing MHV-1 replication and the resulting inflammatory response. The results further suggest that targeting the proteasome may be an effective new treatment for severe coronavirus infections.",,"['Ma, Xue-Zhong', 'Bartczak, Agata', 'Zhang, Jianhua', 'Khattar, Ramzi', 'Chen, Limin', 'Liu, Ming Feng', 'Edwards, Aled', 'Levy, Gary', 'McGilvray, Ian D.']",,,,
,PMC,"Nucleases: Diversity of Structure, Function and Mechanism",http://dx.doi.org/10.1017/S0033583510000181,PMC6320257,,,"Nucleases cleave the phosphodiester bonds of nucleic acids and may be endo or exo, DNases or RNases, topoisomerases, recombinases, ribozymes, or RNA splicing enzymes. In this review I survey nuclease activities with known structures and catalytic machinery and classify them by reaction mechanism and metal ion dependence and by their biological function ranging from DNA replication, recombination, repair, RNA maturation, processing, interference, to defense, nutrient regeneration or cell death. Several general principles emerge from this analysis. There is little correlation between catalytic mechanism and biological function. A single catalytic mechanism can be adapted in a variety of reactions and biological pathways. Conversely a single biological process can often be accomplished by multiple tertiary and quaternary folds and by more than one catalytic mechanism. Two-metal-ion dependent nucleases comprise the largest number of different tertiary folds and mediate the most diverse set of biological functions. Metal-ion dependent cleavage is exclusively associated with exonucleases producing monomucleotides and endonucleases that cleave double- or single-stranded substrates in helical and base-stacked conformations. All metal-ion independent RNases generate 2´,3´-cyclic phosphate products, and all metal-ion independent DNases form phospho-protein intermediates. I also find several previously unnoted relationships between different nucleases and shared catalytic configurations.",,"Yang, Wei",,,,
,PMC,The Human Immune Response to Dengue Virus Is Dominated by Highly Cross-Reactive Antibodies Endowed with Neutralizing and Enhancing Activity,http://dx.doi.org/10.1016/j.chom.2010.08.007,PMC3884547,,,Antibodies protect against homologous Dengue virus (DENV) infection but can precipitate severe dengue by promoting heterotypic virus entry via Fcγ receptors (FcγR). We immortalized memory B cells from individuals after primary or secondary infection and analyzed anti-DENV monoclonal antibodies (mAbs) thus generated. MAbs to envelope (E) protein domain III (DIII) were either serotype specific or cross-reactive and potently neutralized DENV infection. DI/DII- or viral membrane protein prM-reactive mAbs neutralized poorly and showed broad cross-reactivity with the four DENV serotypes. All mAbs enhanced infection at subneutralizing concentrations. Three mAbs targeting distinct epitopes on the four DENV serotypes and engineered to prevent FcγR binding did not enhance infection and neutralized DENV in vitro and in vivo as postexposure therapy in a mouse model of lethal DENV infection. Our findings reveal an unexpected degree of cross-reactivity in human antibodies against DENV and illustrate the potential for an antibody-based therapy to control severe dengue.,,"['Beltramello, Martina', 'Williams, Katherine L.', 'Simmons, Cameron P.', 'Macagno, Annalisa', 'Simonelli, Luca', 'Quyen, Nguyen Than Ha', 'Sukupolvi-Petty, Soila', 'Navarro-Sanchez, Erika', 'Young, Paul R.', 'de Silva, Aravinda M.', 'Rey, Félix A.', 'Varani, Luca', 'Whitehead, Stephen S.', 'Diamond, Michael S.', 'Harris, Eva', 'Lanzavecchia, Antonio', 'Sallusto, Federica']",,,,
,PMC,Sampling port for real time analysis of bioaerosol in whole body exposure system for animal aerosol model development,http://dx.doi.org/10.1016/j.vascn.2010.09.002,PMC3022121,,,"INTRODUCTION: Multiple factors influence the viability of aerosolized bacteria. The delivery of aerosols is affected by chamber conditions (humidity, temperature, and pressure) and bioaerosol characteristics (particle number, particle size distribution, and viable aerosol concentration). Measurement of viable aerosol concentration and particle size is essential to optimize viability and lung delivery. The Madison chamber is widely used to expose small animals to infectious aerosols. METHODS: A multiplex sampling port was added to the Madison chamber to measure the chamber conditions and bioaerosol characteristics. Aerosols of three pathogens (Bacillus anthracis, Yersinia pestis, and Mycobacterium tuberculosis) were generated under constant conditions and their bioaerosol characteristics were analyzed. Airborne microbes were captured using an impinger or BioSampler. The particle size distribution of airborne microbes was determined using an aerodynamic particle sizer (APS). Viable aerosol concentration, spray factor (viable aerosol concentration/inoculum concentration), and dose presented to the mouse were calculated. Dose retention efficiency and viable aerosol retention rate were calculated from the sampler titers to determine the efficiency of microbe retention in lungs of mice. RESULTS: B. anthracis, Y. pestis, and M. tuberculosis aerosols were sampled through the port. The count mean aerodynamic sizes were 0.98, 0.77, and 0.78 μm with geometric standard deviations of 1.60, 1.90, and 2.37, and viable aerosol concentrations in the chamber were 211, 57, and 1 colony-forming unit (CFU)/mL, respectively. Based on the aerosol concentrations, the doses presented to mice for the three pathogens were 2.5e5, 2.2e4 and 464 CFU. DISCUSSION: Using the multiplex sampling port we determined whether the animals were challenged with an optimum bioaerosol based on dose presented and respirable particle size.",,"['Saini, Divey', 'Hopkins, Gregory W.', 'Chen, Ching-ju', 'Seay, Sarah A.', 'Click, Eva M.', 'Lee, Sunhee', 'Hartings, Justin M.', 'Frothingham, Richard']",,,,
,PMC,CHARACTERIZATION OF ANTIBODIES INDUCED BY VACCINATION WITH HEPATITIS C VIRUS ENVELOPE GLYCOPROTEINS,http://dx.doi.org/10.1086/655902,PMC2931414,,,"Hepatitis C virus (HCV) envelope glycoproteins, E1 and E2, were used with MF59 adjuvant as a candidate vaccine for a phase I safety and immunogenicity trial. Ten of the 41 vaccinee sera tested displayed a VSV/HCV surrogate pseudotype neutralization titer of ≥1/20, 15 of the 36 sera tested had a neutralization titer of ≥ 1/400 against HIV/HCV pseudotype, and 10 of the 36 sera tested had a neutralization titer of ≥1/20 of cell culture grown HCVgenotype 1a. Neutralizing sera had increased affinity, and displayed >2 fold higher specific activity to well characterized epitopes on E1/E2, especially to the hypervariable region 1 (HVR1) of E2.",,"['Ray, Ranjit', 'Meyer, Keith', 'Banerjee, Arup', 'Basu, Arnab', 'Coates, Stephen', 'Abrignani, Sergio', 'Houghton, Michael', 'Frey, Sharon E.', 'Belshe, Robert B.']",,,,
,PMC,Novel Immunodominant Peptide Presentation Strategy: a Featured HLA-A*2402-Restricted Cytotoxic T-Lymphocyte Epitope Stabilized by Intrachain Hydrogen Bonds from Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein,http://dx.doi.org/10.1128/JVI.01464-10,PMC2977860,,,"Antigenic peptides recognized by virus-specific cytotoxic T lymphocytes (CTLs) are presented by major histocompatibility complex (MHC; or human leukocyte antigen [HLA] in humans) molecules, and the peptide selection and presentation strategy of the host has been studied to guide our understanding of cellular immunity and vaccine development. Here, a severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid (N) protein-derived CTL epitope, N1 (QFKDNVILL), restricted by HLA-A*2402 was identified by a series of in vitro studies, including a computer-assisted algorithm for prediction, stabilization of the peptide by co-refolding with HLA-A*2402 heavy chain and β(2)-microglobulin (β(2)m), and T2-A24 cell binding. Consequently, the antigenicity of the peptide was confirmed by enzyme-linked immunospot (ELISPOT), proliferation assays, and HLA-peptide complex tetramer staining using peripheral blood mononuclear cells (PBMCs) from donors who had recovered from SARS donors. Furthermore, the crystal structure of HLA-A*2402 complexed with peptide N1 was determined, and the featured peptide was characterized with two unexpected intrachain hydrogen bonds which augment the central residues to bulge out of the binding groove. This may contribute to the T-cell receptor (TCR) interaction, showing a host immunodominant peptide presentation strategy. Meanwhile, a rapid and efficient strategy is presented for the determination of naturally presented CTL epitopes in the context of given HLA alleles of interest from long immunogenic overlapping peptides.",,"['Liu, Jun', 'Wu, Peng', 'Gao, Feng', 'Qi, Jianxun', 'Kawana-Tachikawa, Ai', 'Xie, Jing', 'Vavricka, Christopher J.', 'Iwamoto, Aikichi', 'Li, Taisheng', 'Gao, George F.']",,,,
,PMC,Respiratory Syncytial Virus Induces Host RNA Stress Granules To Facilitate Viral Replication,http://dx.doi.org/10.1128/JVI.00260-10,PMC2976418,,,"Mammalian cell cytoplasmic RNA stress granules are induced during various conditions of stress and are strongly associated with regulation of host mRNA translation. Several viruses induce stress granules during the course of infection, but the exact function of these structures during virus replication is not well understood. In this study, we showed that respiratory syncytial virus (RSV) induced host stress granules in epithelial cells during the course of infection. We also showed that stress granules are distinct from cytoplasmic viral inclusion bodies and that the RNA binding protein HuR, normally found in stress granules, also localized to viral inclusion bodies during infection. Interestingly, we demonstrated that infected cells containing stress granules also contained more RSV protein than infected cells that did not form inclusion bodies. To address the role of stress granule formation in RSV infection, we generated a stable epithelial cell line with reduced expression of the Ras-GAP SH3 domain-binding protein (G3BP) that displayed an inhibited stress granule response. Surprisingly, RSV replication was impaired in these cells compared to its replication in cells with intact G3BP expression. In contrast, knockdown of HuR by RNA interference did not affect stress granule formation or RSV replication. Finally, using RNA probes specific for RSV genomic RNA, we found that viral RNA predominantly localized to viral inclusion bodies but a small percentage also interacted with stress granules during infection. These results suggest that RSV induces a host stress granule response and preferentially replicates in host cells that have committed to a stress response.",,"['Lindquist, Michael E.', 'Lifland, Aaron W.', 'Utley, Thomas J.', 'Santangelo, Philip J.', 'Crowe, James E.']",,,,
,PMC,Management of acute-onset and life-threatening respiratory distress of unusual aetiology,http://dx.doi.org/10.1136/bcr.05.2010.3000,PMC3027714,,,"A 30-year-old female experienced severe acute respiratory distress in her apartment assumed to be due to an allergic asthma. Upon arrival of the emergency physician at the scene the patient was unconscious and cyanotic. Auscultation yielded no respiratory sounds despite visible efforts of the patient. Mask ventilation was virtually impossible. Endotracheal intubation was performed but complicated by a distinct resistance. Ventilation remained difficult, despite antiobstructive medication and deep general anaesthesia. Fiberoptic bronchoscopy in the hospital finally showed a bulk of granulomatous tissue located just above the tracheal bifurcation. Here, the authors report a rare case of acute-onset respiratory distress due to Wegener's granulomatosis.",,"['Radke, Robert M.', 'Kessler, Torsten', 'Lebiedz, Pia']",,,,
,PMC,Impaired immune responses following spinal cord injury lead to reduced ability to control viral infection,http://dx.doi.org/10.1016/j.expneurol.2010.08.036,PMC5029284,,,"Spinal cord injuries disrupt central autonomic pathways that regulate immune function, and increasing evidence suggests that this may cause deficiencies in immune responses in people with spinal cord injuries. Here we analyze the consequences of spinal cord injury (SCI) on immune responses following experimental viral infection of mice. Female C57BL/6 mice received complete crush injuries at either thoracic level 3 (T3) or 9 (T9), and 1 week post-injury, injured mice and un-injured controls were infected with different dosages of mouse hepatitis virus (MHV, a positive-strand RNA virus). Following MHV infection, T3- and T9-injured mice exhibited increased mortality in comparison to un-injured and laminectomy controls. Infection at all dosages resulted in significantly higher viral titer in both T3- and T9-injured mice compared to un-injured controls. Investigation of anti-viral immune responses revealed impairment of cellular infiltration and effector functions in mice with SCI. Specifically, cell-mediated responses were diminished in T3-injured mice, as seen by reduction in virus-specific CD4(+) T lymphocyte proliferation and IFN-γ production and decreased numbers of activated antigen presenting cells compared to infected un-injured mice. Collectively, these data indicate that the inability to control viral replication following SCI is not level dependent and that increased susceptibility to infection is due to suppression of both innate and adaptive immune responses.",,"['Held, Katherine S.', 'Steward, Oswald', 'Blanc, Caroline', 'Lane, Thomas E.']",,,,
,PMC,"RNA granules: the good, the bad and the ugly",http://dx.doi.org/10.1016/j.cellsig.2010.08.011,PMC3001194,,,"Processing bodies (PBs) and Stress granules (SGs) are the founding members of a new class of RNA granules, known as mRNA silencing foci, as they harbor transcripts circumstantially excluded from the translationally active pool. PBs and SGs are able to release mRNAs thus allowing their translation. PBs are constitutive, but respond to stimuli that affect mRNA translation and decay, whereas SGs are specifically induced upon cellular stress, which triggers a global translational silencing by several pathways, including phosphorylation of the key translation initiation factor elF2alpha, and tRNA cleavage among others. PBs and SGs with different composition may coexist in a single cell. These macromolecular aggregates are highly conserved through evolution, from unicellular organisms to vertebrate neurons. Their dynamics is regulated by several signaling pathways, and depends on microfilaments and microtubules, and the cognate molecular motors myosin, dynein, and kinesin. SGs share features with aggresomes and related aggregates of unfolded proteins frequently present in neurodegenerative diseases, and may play a role in the pathology. Virus infections may induce or impair SG formation. Besides being important for mRNA regulation upon stress, SGs modulate the signaling balancing apoptosis and cell survival. Finally, the formation of nuclear stress bodies (nSBs), which share components with SGs, and the assembly of additional cytosolic aggregates containing RNA—the UV granules and the Ire1 foci—, all them induced by specific cell damage factors, contribute to cell survival.",,"['Thomas, María Gabriela', 'Loschi, Mariela', 'Desbats, María Andrea', 'Boccaccio, Graciela Lidia']",,,,
,PMC,"Real-Time Detection of Influenza A, Influenza B, and Respiratory Syncytial Virus A and B in Respiratory Specimens by Use of Nanoparticle Probes",http://dx.doi.org/10.1128/JCM.01118-10,PMC3020893,,,"Seasonal epidemics of influenza and respiratory syncytial virus are responsible for significant morbidity and mortality worldwide. Infrequently, novel or reemergent strains of influenza A virus have caused rapid, severe global pandemics resulting in millions of fatalities. The ability to efficiently and accurately detect and differentiate respiratory viruses is paramount for effective treatment, infection control, and epidemiological surveillance. We evaluated the ability of two FDA-cleared nucleic acid-based tests, the semiautomated respiratory virus nucleic acid test (VRNAT) and the fully automated respiratory virus nucleic acid test SP (RVNAT(SP)) (Nanosphere Inc., Northbrook, IL) to detect influenza A virus, influenza B virus, and respiratory syncytial virus A and B (RSV A/B) from clinical nasopharyngeal swab specimens. Detection of viral RNA in both tests is based on nucleic acid amplification followed by hybridization to capture probes immobilized on a glass slide. A novel technology utilizing gold nanoparticle-conjugated probes is utilized to detect the presence of captured target DNA. This microarray-based approach to detection has proven to be more sensitive than the traditional culture/direct fluorescent-antibody assay (DFA) method for detecting RSV and influenza viruses in clinical specimens, including the novel 2009 H1N1 strain. Specifically, we report 98.0% sensitivity and 96.5% specificity for the VRNAT compared to culture/DFA. Further, the VRNAT detected virus in an additional 58% of specimens that were culture negative. These data were confirmed using bidirectional sequencing. Evaluation of the fully automated RVNAT(SP), which is built on the same detection technology as the VRNAT but contains an updated processor enabling complete automation, revealed the two tests to be functionally equivalent. Thus, the RVNAT(SP) is a fully automated sample-to-result test capable of reliable detection of select respiratory viruses directly from clinical specimens in 3.5 h.",,"['Jannetto, Paul J.', 'Buchan, Blake W.', 'Vaughan, Kimberly A.', 'Ledford, Joellen S.', 'Anderson, Dennis K.', 'Henley, Donald C.', 'Quigley, Neil B.', 'Ledeboer, Nathan A.']",,,,
,PMC,Novel Use of Tryptose Sulfite Cycloserine Egg Yolk Agar for Isolation of Clostridium perfringens during an Outbreak of Necrotizing Enterocolitis in a Neonatal Unit,http://dx.doi.org/10.1128/JCM.01724-10,PMC3020804,,,"Clostridium perfringens has been associated with necrotizing enterocolitis (NEC), which is a serious disease of neonates. Our study describes the novel use of selective tryptose sulfite cycloserine with egg yolk agar (TSC-EYA) during a nursery outbreak. This medium provides a rapid, sensitive, and accurate presumptive identification of C. perfringens.",,"['Kotsanas, Despina', 'Carson, Jolene A.', 'Awad, Milena M.', 'Lyras, Dena', 'Rood, Julian I.', 'Jenkin, Grant A.', 'Stuart, Rhonda L.', 'Korman, Tony M.']",,,,
,PMC,Monomerization of the viral entry inhibitor griffithsin yields insights into the relationship between multivalent binding to high mannose oligosaccharides and antiviral activity,http://dx.doi.org/10.1016/j.str.2010.05.016,PMC3399781,,,"Mutations were introduced to the domain-swapped homodimer of the antiviral lectin griffithsin (GRFT). Whereas several single and double mutants remained dimeric, insertion of either two or four amino acids at the dimerization interface resulted in a monomeric form of the protein (mGRFT). Monomeric character of the modified proteins was confirmed by sedimentation equilibrium ultracentrifugation and by their high resolution X-ray crystal structures, whereas their binding to carbohydrates was assessed by isothermal titration calorimetry. Cell-based antiviral activity assays utilizing different variants of mGRFT indicated that the monomeric form of the lectin had greatly reduced activity against HIV-1, suggesting that the antiviral activity of GRFT stems from crosslinking and aggregation of viral particles via multivalent interactions between GRFT and oligosaccharides present on HIV envelope glycoproteins. Atomic resolution crystal structure of a complex between mGRFT and nonamannoside revealed that a single mGRFT molecule binds to two different nonamannoside molecules through all three carbohydrate-binding sites present on the monomer.",,"['Moulaei, Tinoush', 'Shenoy, Shilpa R.', 'Giomarelli, Barbara', 'Thomas, Cheryl', 'McMahon, James B.', 'Dauter, Zbigniew', 'O’Keefe, Barry R.', 'Wlodawer, Alexander']",,,,
,PMC,Nuclear Import of Cytoplasmic Poly(A) Binding Protein Restricts Gene Expression via Hyperadenylation and Nuclear Retention of mRNA,http://dx.doi.org/10.1128/MCB.00600-10,PMC2953054,,,"Poly(A) tail length is emerging as an important marker of mRNA fate, where deviations from the canonical length can signal degradation or nuclear retention of transcripts. Pathways regulating polyadenylation thus have the potential to broadly influence gene expression. Here we demonstrate that accumulation of cytoplasmic poly(A) binding protein (PABPC) in the nucleus, which can occur during viral infection or other forms of cellular stress, causes mRNA hyperadenylation and nuclear accumulation of poly(A) RNA. This inhibits gene expression but does not affect mRNA stability. Unexpectedly, PABPC-induced hyperadenylation can occur independently of mRNA 3′-end processing yet requires the canonical mRNA poly(A) polymerase II. We find that nuclear PABPC-induced hyperadenylation is triggered by multiple divergent viral factors, suggesting that altering the subcellular localization of PABPC may be a commonly used mechanism to regulate cellular gene expression in a polyadenylation-linked manner.",,"['Kumar, G. Renuka', 'Glaunsinger, Britt A.']",,,,
,PMC,The Ubiquitin-Proteasome System Regulates the Accumulation of Turnip yellow mosaic virus RNA-Dependent RNA Polymerase during Viral Infection([W]),http://dx.doi.org/10.1105/tpc.109.072090,PMC2965540,,,"Replication of positive-strand RNA viruses, the largest group of plant viruses, is initiated by viral RNA-dependent RNA polymerase (RdRp). Given its essential function in viral replication, understanding the regulation of RdRp is of great importance. Here, we show that Turnip yellow mosaic virus (TYMV) RdRp (termed 66K) is degraded by the proteasome at late time points during viral infection and that the accumulation level of 66K affects viral RNA replication in infected Arabidopsis thaliana cells. We mapped the cis-determinants responsible for 66K degradation within its N-terminal noncatalytic domain, but we conclude that 66K is not a natural N-end rule substrate. Instead, we show that a proposed PEST sequence within 66K functions as a transferable degradation motif. In addition, several Lys residues that constitute target sites for ubiquitylation were mapped; mutation of these Lys residues leads to stabilization of 66K. Altogether, these results demonstrate that TYMV RdRp is a target of the ubiquitin-proteasome system in plant cells and support the idea that proteasomal degradation may constitute yet another fundamental level of regulation of viral replication.",,"['Camborde, Laurent', 'Planchais, Séverine', 'Tournier, Vincent', 'Jakubiec, Anna', 'Drugeon, Gabrièle', 'Lacassagne, Emmanuelle', 'Pflieger, Stéphanie', 'Chenon, Mélanie', 'Jupin, Isabelle']",,,,
,PMC,The Role of Viral Respiratory Infections in Asthma and Asthma Exacerbations,http://dx.doi.org/10.1016/S0140-6736(10)61380-3,PMC2972660,,,"Viral respiratory tract infections are frequent and usually self-limited illnesses. For patients at risk for asthma, or with existing asthma, viral respiratory tract infections can have a profound effect on the expression of disease or loss of control. New evidence has shown that wheezing episodes early in life with the common cold virus, human rhinovirus, is a major risk factor for the later diagnosis of asthma at age six years. For those with existing asthma, exacerbations are a major cause of morbidity, need for acute care and, rarely, death. Viral respiratory tract infections, most frequently with rhinovirus, are the predominant microorganisms associated with asthma exacerbations. Evidence is also emerging that deficiencies in antiviral activity and the integrity of the airway epithelial barrier may make individuals with asthma more likely to have severe viral respiratory infections of the lower airway, and thus increase the risk of exacerbation. Given the influences of respiratory viruses on many aspects of asthma, efforts to understand the mechanisms and risk factors by which these airway infections cause changes in airway pathophysiology are a first step in improved treatment.",,"['Busse, William W.', 'Lemanske, Robert F.', 'Gern, James E.']",,,,
,PMC,Diagnosis of Novel Pandemic Influenza Virus 2009 H1N1 in Hospitalized Patients,http://dx.doi.org/10.1007/s13337-010-0005-0,PMC3550770,,,"A real-time RT-PCR assay was standardized and evaluated for the detection of the recent pandemic 2009 H1N1 strain that circulated around the world causing colossal loss of human life. We amplified the conserved regions of the hemagglutinin (HA) gene of 438 clinical specimens using real-time RT-PCR assay for rapid identification of pandemic influenza virus. The real-time RT-PCR was optimized and the primers and probes were tested against a panel of known negative and positive controls. RNA isolated from the HeLa cell line served as quality control. The conventional RT-PCR which is an established method of influenza virus diagnosis was compared to real-time RT-PCR. Of 438 clinical specimens tested, 212 specimens were found positive for influenza A virus (SD 46.669) in which 139 specimens were diagnosed positive for the pandemic 2009 H1N1 while 73 were the seasonal influenza viruses. We report that the real-time RT-PCR assay offers both, a high sensitivity and specificity when compared with the traditional identification method. The real-time RT-PCR assay allows rapid identification of the pandemic swine 2009-H1N1 at very low viral loads that are negative by the traditional RT-PCR. This optimized assay can be a very useful tool to assist both epidemiologists and the clinicians.",,"['Kumar, P.', 'Kumar, B.', 'Gupta, A.', 'Sharma, B.', 'Vijayan, V. K.', 'Khare, S.', 'Singh, V.', 'Daga, M. K.', 'Chadha, M. S.', 'Mishra, A. C.', 'Kaur, H.', 'Khanna, M.']",,,,
,PMC,The ‘One Health’ paradigm: Time for infectious diseases clinicians to take note?,,PMC2951799,,,,,"['Fisman, David N', 'Laupland, Kevin B']",,,,
,PMC,Infectious Causes of Stillbirth: A Clinical Perspective,http://dx.doi.org/10.1097/GRF.0b013e3181eb6620,PMC3893929,,,"Untreated infection may cause stillbirth by several mechanisms, including direct fetal infection, placental damage, and severe maternal illness. Many bacteria, viruses, and protozoa have been associated with stillbirth. In developed countries, up to 24% of stillbirths have been attributed to infection, although with increased availability of sophisticated diagnostics and rigorous screening, it appears likely that higher numbers may actually be associated with infection. In developed countries, ascending bacterial infection is usually the most common infectious cause of stillbirth, with a number of viral infections also an important factor. Screening, prevention and treatment of maternal infections are important to reduce stillbirth risk.",,"['McClure, Elizabeth M.', 'Dudley, Donald J.', 'Reddy, Uma', 'Goldenberg, Robert L.']",,,,
,PMC,NONBACTERIAL MYOSITIS,http://dx.doi.org/10.1007/s11908-010-0118-z,PMC3043460,,,"Infectious myositis is defined as an infection of a skeletal muscle. Infectious myositis is most commonly caused by bacteria; however, a variety of viral, parasitic, and fungal agents may also cause myositis. The pathogenesis of nonbacterial infectious myositis is via direct infection of the musculature or immune mechanisms. Symptoms typically include muscular pain, tenderness, swelling, and/or weakness. The diagnosis of the specific microbe is often suggested by the presence of concordant clinical signs and symptoms, a detailed medical/travel history, and laboratory data. For example, immunocompromised hosts have a heightened risk of fungal myositis, whereas the presence of a travel history to an endemic location and/or eosinophilia may suggest a parasitic cause. Definitive diagnosis requires detecting the organism by specific laboratory testing including serologies, histopathology, and/or cultures. Treatment entails antimicrobial agents against the pathogen, with consideration for surgical drainage for focal purulent collections within the musculature.",,"Crum-Cianflone, Nancy F.",,,,
,PMC,Newcastle disease virus-like particles as a platform for the development of vaccines for human and agricultural pathogens,http://dx.doi.org/10.2217/fvl.10.50,PMC3039435,,,"Vaccination is the single most effective way to control viral diseases. However, many currently used vaccines have safety concerns, efficacy issues or production problems. For other viral pathogens, classic approaches to vaccine development have, thus far, been unsuccessful. Virus-like particles (VLPs) are increasingly being considered as vaccine candidates because they offer significant advantages over many currently used vaccines or developing vaccine technologies. VLPs formed with structural proteins of Newcastle disease virus, an avian paramyxovirus, are a potential vaccine candidate for Newcastle disease in poultry. More importantly, these VLPs are a novel, uniquely versatile VLP platform for the rapid construction of effective vaccine candidates for many human pathogens, including genetically complex viruses and viruses for which no vaccines currently exist.",,"Morrison, Trudy G",,,,
,PMC,High content cellular immune profiling reveals differences between rhesus monkeys and men,http://dx.doi.org/10.1111/j.1365-2567.2010.03284.x,PMC2966765,,,"A better understanding of similarities and differences in the composition of the cellular immune system in non-human primates (NHPs) compared with human subjects will improve the interpretation of preclinical studies. It will also aid in addressing the usefulness of NHPs as subjects for studying chronic diseases, vaccine development and immune reconstitution. We employed high content colour flow cytometry and analysed simultaneously the expression of CD3, CD4, CD8α, CD8β, CD16/CD56, CD45RA, CCR7, CD27, CD28, CD107a and the interleukin-7 receptor α-chain (IL-7Rα) in peripheral blood mononuclear cells (PBMCs) of 27 rhesus macaques and 16 healthy human subjects. Regulatory T cells (Tregs) were identified using anti-CD3, -CD4, -CD25, -FoxP3, and -IL-7Rα monoclonal antibodies. Responsiveness to IL-7 was gauged in a signal transducer and activation of transcription 5 (STAT-5) phosphorylation assay. Human and NHP PBMCs showed a similar T-cell composition pattern with some remarkable differences. Similarities: human and NHP CD4(+) and CD8(+) cells showed a similar STAT-5 phosphorylation pattern in response to IL-7. Multicolour flow cytometric analysis identified a CD4(+) CD8αα(+) CD8αβ(+) T-cell population in NHPs as well as in human subjects that expressed the degranulation marker CD107a and may represent a unique CD4(+) T-cell subset endowed with cytotoxic capacity. Differences: we identified in PBMCs from NHPs a higher proportion (5·16% in CD3(+) T cells) of CD8αα(+) T cells when compared with human donors (1·22% in CD3(+) T cells). NHP CD8αα(+) T cells produced tumour necrosis factor-α / interferon-γ (TNF-α/IFN-γ) or TNF-α, whereas human CD8αα(+) T cells produced simultaneously TNF-α/IFN-γ and IL-2. A minor percentage of human CD8(+) T cells expressed CD25(bright) and FoxP3 (0·01%). In contrast, 0·07% of NHP CD8(+) T cells exhibited the CD25(bright) FoxP3(+) phenotype. PBMCs from NHPs showed less IL-7Rα-positive events in all T-cell subsets including CD4(+) Tregs (median 5%) as compared with human (median 12%). The data visualize commonalities and differences in immune cell subsets in humans and NHPs, most of them in long-lived memory cells and cells with suppressive functions. This provides a matrix to assess future efforts to study diseases and vaccines in NHPs.",,"['Magalhaes, Isabelle', 'Vudattu, Nalini K', 'Ahmed, Raija K', 'Kühlmann-Berenzon, Sharon', 'Ngo, Yen', 'Sizemore, Donata R', 'Wehlin, Lena', 'Weichold, Frank', 'Andersson, Jan', 'Skeiky, Yasir AW', 'Sadoff, Jerry', 'Gaines, Hans', 'Thorstensson, Rigmor', 'Spångberg, Mats', 'Maeurer, Markus J']",,,,
,PMC,CD4(+) T cells against human papillomavirus-18 E7 in patients with high-grade cervical lesions associate with the absence of the virus in the cervix,http://dx.doi.org/10.1111/j.1365-2567.2010.03277.x,PMC2966761,,,"Cervical neoplastic lesions are associated with infection by high-risk human papilloma-viruses (HPV). The two genotypes most frequently found in the lesions are HPV-16 and HPV-18 with a prevalence of 50–60% and 15–18%, respectively. The E6 and E7 viral oncoproteins are involved in the transformation process and represent foreign antigens for the host. We previously reported that anti-HPV-18 E6 CD4(+) T cells are present in patients with high-grade HPV-18-expressing cervical lesions but also in 50% of the total consecutive patients tested, independently of the HPV type carried. These results indicated that HPV-18 E6 is immunogenic and suggested that all responsive patients, irrespective of the HPV expressed, had encountered HPV-18 and cleared the infection. Here, we investigated anti-HPV-18 E7 CD4(+) T-cell immunity in a cohort of 23 HPV-18 E6-responsive patients. We found that, although E7-specific CD4(+) T cells were present in all women, a robust T helper type (Th1)/Th2 type response against E7 was associated with HPV-18-negative status, suggesting that indeed these patients might have cleared the virus. In agreement with this hypothesis, we found strong anti-E7 CD4(+) T-cell immunity in 20% of 24 healthy donors without evidence of disease. In contrast, a robust Th1/Th2 type response against E6 but not E7 correlated with a lack of disease relapse and/or infection recurrence but did not discriminate between HPV-18-positive and HPV-18-negative patients. Collectively, our data suggest different roles for anti-HPV-18 E6 and E7 CD4(+) T cells in anti-viral and anti-tumour immunity.",,"['Seresini, Samantha', 'Origoni, Massimo', 'Caputo, Luigi', 'Lillo, Flavia', 'Longhi, Renato', 'Vantini, Simone', 'Paganoni, Anna Maria', 'Protti, Maria Pia']",,,,
,PMC,A Comprehensive Laboratory Animal Facility Pandemic Response Plan,,PMC2949433,,,"The potential of a severe influenza pandemic necessitates the development of an organized, rational plan for continued laboratory animal facility operation without compromise of the welfare of animals. A comprehensive laboratory animal program pandemic response plan was integrated into a university-wide plan. Preparation involved input from all levels of organizational hierarchy including the IACUC. Many contingencies and operational scenarios were considered based on the severity and duration of the influenza pandemic. Trigger points for systematic action steps were based on the World Health Organization's phase alert criteria. One extreme scenario requires hibernation of research operations and maintenance of reduced numbers of laboratory animal colonies for a period of up to 6 mo. This plan includes active recruitment and cross-training of volunteers for essential personnel positions, protective measures for employee and family health, logistical arrangements for delivery and storage of food and bedding, the removal of waste, and the potential for euthanasia. Strategies such as encouraging and subsidizing cryopreservation of unique strains were undertaken to protect valuable research assets and intellectual property. Elements of this plan were put into practice after escalation of the pandemic alerts due to influenza A (H1N1) in April 2009.",,"['Roble, Gordon S', 'Lingenhol, Naomi M', 'Baker, Bryan', 'Wilkerson, Amy', 'Tolwani, Ravi J']",,,,
,PMC,Developing syndrome definitions based on consensus and current use,http://dx.doi.org/10.1136/jamia.2010.003210,PMC2995670,,,"OBJECTIVE: Standardized surveillance syndromes do not exist but would facilitate sharing data among surveillance systems and comparing the accuracy of existing systems. The objective of this study was to create reference syndrome definitions from a consensus of investigators who currently have or are building syndromic surveillance systems. DESIGN: Clinical condition–syndrome pairs were catalogued for 10 surveillance systems across the United States and the representatives of these systems were brought together for a workshop to discuss consensus syndrome definitions. RESULTS: Consensus syndrome definitions were generated for the four syndromes monitored by the majority of the 10 participating surveillance systems: Respiratory, gastrointestinal, constitutional, and influenza-like illness (ILI). An important element in coming to consensus quickly was the development of a sensitive and specific definition for respiratory and gastrointestinal syndromes. After the workshop, the definitions were refined and supplemented with keywords and regular expressions, the keywords were mapped to standard vocabularies, and a web ontology language (OWL) ontology was created. LIMITATIONS: The consensus definitions have not yet been validated through implementation. CONCLUSION: The consensus definitions provide an explicit description of the current state-of-the-art syndromes used in automated surveillance, which can subsequently be systematically evaluated against real data to improve the definitions. The method for creating consensus definitions could be applied to other domains that have diverse existing definitions.",,"['Chapman, Wendy W', 'Dowling, John N', 'Baer, Atar', 'Buckeridge, David L', 'Cochrane, Dennis', 'Conway, Michael A', 'Elkin, Peter', 'Espino, Jeremy', 'Gunn, Julia E', 'Hales, Craig M', 'Hutwagner, Lori', 'Keller, Mikaela', 'Larson, Catherine', 'Noe, Rebecca', 'Okhmatovskaia, Anya', 'Olson, Karen', 'Paladini, Marc', 'Scholer, Matthew', 'Sniegoski, Carol', 'Thompson, David', 'Lober, Bill']",,,,
,PMC,Human Respiratory Syncytial Virus in Children with Acute Respiratory Tract Infections in China,http://dx.doi.org/10.1128/JCM.00179-10,PMC3020873,,,"There are limited data on the prevalence and clinical and molecular characterization of human respiratory syncytial virus (HRSV) in children with acute respiratory tract infections (ARTIs) in China. From December 2006 to March 2009, 894 nasopharyngeal aspirates (NPAs) were collected from children under 14 years of age with ARTIs. Samples were screened for HRSV and genotyped by reverse transcription-PCR (RT-PCR) and sequencing. Demographic and clinical information was recorded. A total of 38.14% (341/894) of samples were positive for HRSV. Phylogenetic analysis revealed that 60.4% of the selected 227 RSV strains were GA2, 34.4% were BA, 4.8% were GB2, and 0.4% were GB3. A total of 40.47% of all of the RSV-positive samples were coinfected with other respiratory viruses, and adenovirus was the most common additional respiratory virus. No statistical differences were found in the frequency of diagnosis and symptoms between the coinfection group and monoinfection group. Additionally, no statistical differences were found in epidemiological characterizations or disease severity between genotype BA- and GA2-positive patients, except for a greater frequency of lower respiratory tract infections (LRTIs) (mostly bronchitis)with BA. HRSV is the most important viral pathogen in Chinese children with ARTIs. Four genotypes (i.e., GA2, BA, GB2, and GB3) circulate locally, and the predominant genotype may shift between seasons. Coinfection with other viruses does not affect disease severity. HRSV genotypes were not associated with different epidemiological characterizations or disease severity.",,"['Zhang, Rong-Fang', 'Jin, Yu', 'Xie, Zhi-Ping', 'Liu, Na', 'Yan, Kun-Long', 'Gao, Han-Chun', 'Song, Jing-Rong', 'Yuan, Xin-Hui', 'Xiao, Ni-Guang', 'Guo, Ming-Wei', 'Zhou, Qiong-Hua', 'Hou, Yun-De', 'Duan, Zhaojun']",,,,
,PMC,Divergent Motifs but Overlapping Binding Repertoires of Six HLA-DQ Molecules Frequently Expressed in the Worldwide Human Population,http://dx.doi.org/10.4049/jimmunol.1001006,PMC3307390,,,"Knowledge of the binding repertoires and specificities of HLA-DQ molecules is somewhat limited and contradictory, partly because of the scarcity of reports addressing some of the most common molecules and possibly because of the diversity of the techniques used. In this paper, we report the development of high-throughput binding assays for the six most common DQ molecules in the general worldwide population. Using comprehensive panels of single substitution analogs of specific ligands, we derived detailed binding motifs for DQA1*0501/DQB1*0301, DQA1*0401/DQB1*0402, and DQA1*0101/DQB1*0501 and more detailed motifs for DQA1*0501/DQB1*0201, DQA1*0301/DQB1*0302, and DQA1*0102/DQB1*0602, previously characterized on the basis of sets of eluted ligands and/or limited sets of substituted peptides. In contrast to what has previously been observed for DR and DP molecules, DQ motifs were generally less clearly defined in terms of chemical specificity and, strikingly, had little overlap with each other. However, testing a panel of peptides spanning a set of Phleum pratense Ags, and panels of known DQ epitopes, revealed a surprisingly significant and substantial overlap in the repertoire of peptides bound by these DQ molecules. Although the mechanism underlying these apparently contradictory findings is not clear, it likely reflects the peculiar mode of interaction between DQ (and not DR or DP) molecules and their peptide ligands. Because the DQ molecules studied are found in >85% of the general human population, these findings have important implications for epitope identification studies and monitoring of DQ-restricted immune responses.",,"['Sidney, John', 'Steen, Amiyah', 'Moore, Carrie', 'Ngo, Sandy', 'Chung, Jolan', 'Peters, Bjoern', 'Sette, Alessandro']",,,,
,PMC,Microbe Hunting,http://dx.doi.org/10.1128/MMBR.00007-10,PMC2937520,,,"Summary: Platforms for pathogen discovery have improved since the days of Koch and Pasteur; nonetheless, the challenges of proving causation are at least as daunting as they were in the late 1800s. Although we will almost certainly continue to accumulate low-hanging fruit, where simple relationships will be found between the presence of a cultivatable agent and a disease, these successes will be increasingly infrequent. The future of the field rests instead in our ability to follow footprints of infectious agents that cannot be characterized using classical microbiological techniques and to develop the laboratory and computational infrastructure required to dissect complex host-microbe interactions. I have tried to refine the criteria used by Koch and successors to prove linkage to disease. These refinements are working constructs that will continue to evolve in light of new technologies, new models, and new insights. What will endure is the excitement of the chase. Happy hunting!",,"Lipkin, W. Ian",,,,
,PMC,Development of a symptom score for clinical studies to identify children with a documented viral upper respiratory tract infection,http://dx.doi.org/10.1203/PDR.0b013e3181e9f3a0,PMC2921955,,,"The objective of this study was to develop a symptom scoring system for use in clinical studies that differentiates children with cold symptoms who have an identifiable viral etiology for their upper respiratory tract infection (URI) from those in whom no virus is detected. Nasal swabs for PCR testing for identification of respiratory viruses were obtained on children 2–11 years old at baseline and when parents thought their child was developing a cold. Parental-recorded severity of specific symptoms in children with and without a documented viral URI were compared. Nasal swabs were obtained on 108 children whose parents reported their child was developing a cold. A viral etiology was identified in 62/108 (57.4%) samples. Symptom measures that best differentiated children with a viral etiology from those without were significant runny nose and significant cough on day 1 through day 4 of the illness. A URI symptom score was developed based on these symptoms, with a sensitivity of 81.4%, specificity of 61.9% and accuracy of 73.3%. Parental impression is only a moderately accurate predictor of viral URI in children. Our URI symptom score provided a more accurate method for identifying children with viral URIs for clinical studies.",,"['Taylor, James A.', 'Weber, Wendy J.', 'Martin, Emily T.', 'McCarty, Rachelle L.', 'Englund, Janet A.']",,,,
,PMC,Proteomic analysis identifies highly antigenic proteins on exosomes from M. tuberculosis-infected and culture filtrate protein-treated macrophages,http://dx.doi.org/10.1002/pmic.200900840,PMC3664454,,,"Exosomes are small 30–100 nm membrane vesicles released from hematopoietic and non-hematopoietic cells and function to promote intercellular communication. They are generated through fusion of multivesicular bodies with the plasma membrane and release of interluminal vesicles. Previous studies from our laboratory demonstrated that macrophages infected with Mycobacterium release exosomes that promote activation of both innate and acquired immune responses; however, the components present on exosomes inducing these host responses were not defined. The present study used LC-MS/MS to identify 41 mycobacterial proteins present on exosomes released from M. tuberculosis-infected J774 cells. Many of these proteins have been characterized as highly immunogenic. Further, since most of the mycobacterial proteins identified are actively secreted, we hypothesized that macrophages treated with M. tuberculosis culture filtrate proteins (CFP) would release exosomes containing mycobacterial proteins. We found 29 M. tuberculosis proteins in exosomes released from CFP-treated J774 cells, the majority of which were also present on exosomes isolated from M. tuberculosis-infected cells. The exosomes from CFP-treated J774 cells could promote macrophage and dendritic cell activation as well as activation of naïve T cells in vivo. These results suggest that exosomes containing M. tuberculosis antigens may be alternative approach to developing a tuberculosis vaccine.",,"['Giri, Pramod K.', 'Kruh, Nicole A.', 'Dobos, Karen M.', 'Schorey, Jeff S.']",,,,
,PMC,Novel endoribonucleases as central players in various pathways of eukaryotic RNA metabolism,http://dx.doi.org/10.1261/rna.2237610,PMC2924532,,,"For a long time it has been assumed that the decay of RNA in eukaryotes is mainly carried out by exoribonucleases, which is in contrast to bacteria, where endoribonucleases are well documented to initiate RNA degradation. In recent years, several as yet unknown endonucleases have been described, which has changed our view on eukaryotic RNA metabolism. Most importantly, it was shown that the primary eukaryotic 3′ → 5′ exonuclease, the exosome complex has the ability to endonucleolytically cleave its physiological RNA substrates, and novel endonucleases involved in both nuclear and cytoplasmic RNA surveillance pathways were discovered concurrently. In addition, endoribonucleases responsible for long-known processing steps in the maturation pathways of various RNA classes were recently identified. Moreover, one of the most intensely studied RNA decay pathways—RNAi—is controlled and stimulated by the action of different endonucleases. Furthermore, endoribonucleolytic cleavages executed by various enzymes are also the hallmark of RNA degradation and processing in plant chloroplasts. Finally, multiple context-specific endoribonucleases control qualitative and/or quantitative changes of selected transcripts under particular conditions in different eukaryotic organisms. The aim of this review is to discuss the impact of all of these discoveries on our current understanding of eukaryotic RNA metabolism.",,"['Tomecki, Rafal', 'Dziembowski, Andrzej']",,,,
,PMC,Membrane-shaping host reticulon proteins play crucial roles in viral RNA replication compartment formation and function,http://dx.doi.org/10.1073/pnas.1011105107,PMC2941330,,,"Positive-strand RNA viruses replicate their genomes on membranes with virus-induced rearrangements such as single- or double-membrane vesicles, but the mechanisms of such rearrangements, including the role of host proteins, are poorly understood. Brome mosaic virus (BMV) RNA synthesis occurs in ≈70 nm, negatively curved endoplasmic reticulum (ER) membrane invaginations induced by multifunctional BMV protein 1a. We show that BMV RNA replication is inhibited 80–90% by deleting the reticulon homology proteins (RHPs), a family of membrane-shaping proteins that normally induce and stabilize positively curved peripheral ER membrane tubules. In RHP-depleted cells, 1a localized normally to perinuclear ER membranes and recruited the BMV 2a(pol) polymerase. However, 1a failed to induce ER replication compartments or to recruit viral RNA templates. Partial RHP depletion allowed formation of functional replication vesicles but reduced their diameter by 30–50%. RHPs coimmunoprecipitated with 1a and 1a expression redirected >50% of RHPs from peripheral ER tubules to the interior of BMV-induced RNA replication compartments on perinuclear ER. Moreover, RHP-GFP fusions retained 1a interaction but shifted 1a-induced membrane rearrangements from normal vesicles to double membrane layers, a phenotype also induced by excess 1a-interacting 2a(pol). Thus, RHPs interact with 1a, are incorporated into RNA replication compartments, and are required for multiple 1a functions in replication compartment formation and function. The results suggest possible RHP roles in the bodies and necks of replication vesicles.",,"['Diaz, Arturo', 'Wang, Xiaofeng', 'Ahlquist, Paul']",,,,
,PMC,Environmental factors preceding illness onset differ in phenotypes of the juvenile idiopathic inflammatory myopathies,http://dx.doi.org/10.1093/rheumatology/keq277,PMC2981509,,,"Objective. To assess whether certain environmental factors temporally associated with the onset of juvenile idiopathic inflammatory myopathies (JIIMs) differ between phenotypes. Methods. Physicians completed questionnaires regarding documented infections, medications, immunizations and an open-ended question about other noted exposures within 6 months before illness onset for 285 patients with probable or definite JIIM. Medical records were reviewed for 81% of the patients. Phenotypes were defined by standard clinical and laboratory measures. Results. Sixty per cent of JIIM patients had a reported exposure within 6 months before illness onset. Most patients (62%) had one recorded exposure, 26% had two and 12% had three to five exposures. Patients older than the median age at diagnosis, those with a longer delay to diagnosis and those with anti-signal recognition particle autoantibodies had a higher frequency of documented exposures [odds ratios (ORs) 95% CI 3.4, 31]. Infections were the most common exposure and represented 44% of the total number of reported exposures. Non-infectious exposures included medications (18%), immunizations (11%), stressful life events (11%) and unusual sun exposure (7%). Exposures varied by age at diagnosis, race, disease course and the presence of certain myositis autoantibodies. Conclusion. The JIIMs may be related to multiple exposures and these appear to vary among phenotypes.",,"['Rider, Lisa G.', 'Wu, Lan', 'Mamyrova, Gulnara', 'Targoff, Ira N.', 'Miller, Frederick W.']",,,,
,PMC,SARS-Coronavirus Protein 6 Conformations Required to Impede Protein Import into the Nucleus,http://dx.doi.org/10.1016/j.virusres.2010.08.017,PMC2954772,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) genome encodes eight accessory proteins. Accessory protein 6 is a 63-residue amphipathic peptide that accelerates coronavirus infection kinetics in cell culture and in mice. Protein 6 is minimally bifunctional, with an N-terminal lipophilic part implicated in accelerating viral growth and a C-terminal hydrophilic part interfering with general protein import into the nucleus. This interference with nuclear import requires interaction between protein 6 and cellular karyopherins, a process that typically involves nuclear localization signal (NLS) motifs. Here we dissected protein 6 using site-directed mutagenesis and found no evidence for a classical NLS. Furthermore, we found that the C-terminal tail of protein 6 impeded nuclear import only in the context of a lipophilic N-terminus, which could be derived from membrane proteins unrelated to protein 6. These findings are discussed in the context of the proposed protein 6 structure.",,"['Hussain, Snawar', 'Gallagher, Tom']",,,,
,PMC,Rapid Detection of Respiratory Tract Viral Infections and Coinfections in Patients with Influenza-Like Illnesses by Use of Reverse Transcription-PCR DNA Microarray Systems,http://dx.doi.org/10.1128/JCM.00733-10,PMC3020852,,,"We prospectively tested 95 nasal swabs or nasopharyngeal aspirates taken from 56 adults and 39 children visiting the Reims University Medical Centre (northern France) for influenza-like illnesses (ILI) during the early stage of the French influenza A/H1N1v pandemic (October 2009). Respiratory samples were tested using a combination of two commercially available reverse transcription-PCR (RT-PCR) DNA microarray systems allowing rapid detection of influenza A virus strains, including the new A/H1N1v strain as well as 20 other common or newly discovered respiratory viruses. Concomitantly, a generic and classical real-time RT-PCR assay was performed to detect all circulating influenza A virus strains in the same samples. Of the 95 respiratory samples tested, 30 (31%) were positive for the detection of influenza A/H1N1v virus infection by both RT-PCR DNA microarray and classical real-time RT-PCR detection assays. Among the infections, 25 (83%) were monoinfections, whereas 5 (17%) were multiple infections associating influenza A/H1N1v virus with coronavirus (CoV), human bocavirus (HBoV), respiratory syncytial virus (RSV), or human rhinoviruses (HRVs). Of the 95 respiratory samples tested, 35 (37%) were positive for respiratory viruses other than influenza A/H1N1v virus. Among these infections, we observed 30 monoinfections (HRVs [63%], parainfluenza viruses [PIVs] [20%]), influenza A/H3N2 virus [6%], coronavirus [4%], and HBoV [4%]) and 5 multiple infections, in which HRVs and PIVs were the most frequently detected viruses. No specific single or mixed viral infections appeared to be associated significantly with secondary hospitalization in infectious disease or intensive care departments during the study period (P > 0.5). The use of RT-PCR DNA microarray systems in clinical virology practice allows the rapid and accurate detection of conventional and newly discovered viral respiratory pathogens in patients suffering from ILI and therefore could be of major interest for development of new epidemiological survey systems for respiratory viral infections.",,"['Renois, Fanny', 'Talmud, Déborah', 'Huguenin, Antoine', 'Moutte, Lauryane', 'Strady, Christophe', 'Cousson, Joel', 'Lévêque, Nicolas', 'Andréoletti, Laurent']",,,,
,PMC,An RNA Pseudoknot Is Required for Production of Yellow Fever Virus Subgenomic RNA by the Host Nuclease XRN1,http://dx.doi.org/10.1128/JVI.01047-10,PMC2953177,,,"Cells and mice infected with arthropod-borne flaviviruses produce a small subgenomic RNA that is colinear with the distal part of the viral 3′-untranslated region (UTR). This small subgenomic flavivirus RNA (sfRNA) results from the incomplete degradation of the viral genome by the host 5′-3′ exonuclease XRN1. Production of the sfRNA is important for the pathogenicity of the virus. This study not only presents a detailed description of the yellow fever virus (YFV) sfRNA but, more importantly, describes for the first time the molecular characteristics of the stalling site for XRN1 in the flavivirus genome. Similar to the case for West Nile virus, the YFV sfRNA was produced by XRN1. However, in contrast to the case for other arthropod-borne flaviviruses, not one but two sfRNAs were detected in YFV-infected mammalian cells. The smaller of these two sfRNAs was not observed in infected mosquito cells. The larger sfRNA could also be produced in vitro by incubation with purified XRN1. These two YFV sfRNAs formed a 5′-nested set. The 5′ ends of the YFV sfRNAs were found to be just upstream of the previously predicted RNA pseudoknot PSK3. RNA structure probing and mutagenesis studies provided strong evidence that this pseudoknot structure was formed and served as the molecular signal to stall XRN1. The sequence involved in PSK3 formation was cloned into the Sinrep5 expression vector and shown to direct the production of an sfRNA-like RNA. These results underscore the importance of the RNA pseudoknot in stalling XRN1 and also demonstrate that it is the sole viral requirement for sfRNA production.",,"['Silva, Patrícia A. G. C.', 'Pereira, Carina F.', 'Dalebout, Tim J.', 'Spaan, Willy J. M.', 'Bredenbeek, Peter J.']",,,,
,PMC,Porcine Reproductive and Respiratory Syndrome Virus Inhibits Type I Interferon Signaling by Blocking STAT1/STAT2 Nuclear Translocation,http://dx.doi.org/10.1128/JVI.00655-10,PMC2953160,,,"Type I interferons (IFNs) IFN-α/β play an important role in innate immunity against viral infections by inducing antiviral responses. Porcine reproductive and respiratory syndrome virus (PRRSV) inhibits the synthesis of type I IFNs. However, whether PRRSV can inhibit IFN signaling is less well understood. In the present study, we found that PRRSV interferes with the IFN signaling pathway. The transcript levels of IFN-stimulated genes ISG15 and ISG56 and protein level of signal transducer and activator of transcription 2 (STAT2) in PRRSV VR2385-infected MARC-145 cells were significantly lower than those in mock-infected cells after IFN-α treatment. IFN-induced phosphorylation of both STAT1 and STAT2 and their heterodimer formation in the PRRSV-infected cells were not affected. However, the majority of the STAT1/STAT2/IRF9 (IFN regulatory factor 9) heterotrimers remained in the cytoplasm of PRRSV-infected cells, which indicates that the nuclear translocation of the heterotrimers was blocked. Overexpression of NSP1β of PRRSV VR2385 inhibited expression of ISG15 and ISG56 and blocked nuclear translocation of STAT1, which suggests that NSP1β might be the viral protein responsible for the inhibition of IFN signaling. PRRSV infection in primary porcine pulmonary alveolar macrophages (PAMs) also inhibited IFN-α-stimulated expression of the ISGs and the STAT2 protein. In contrast, a licensed low-virulence vaccine strain, Ingelvac PRRS modified live virus (MLV), activated expression of IFN-inducible genes, including those of chemokines and antiviral proteins, in PAMs without the addition of external IFN and had no detectable effect on IFN signaling. These findings suggest that PRRSV interferes with the activation and signaling pathway of type I IFNs by blocking ISG factor 3 (ISGF3) nuclear translocation.",,"['Patel, Deendayal', 'Nan, Yuchen', 'Shen, Meiyan', 'Ritthipichai, Krit', 'Zhu, Xiaoping', 'Zhang, Yan-Jin']",,,,
,PMC,The Coronavirus Nucleocapsid Protein Is Dynamically Associated with the Replication-Transcription Complexes,http://dx.doi.org/10.1128/JVI.00569-10,PMC2953146,,,"The coronavirus nucleocapsid (N) protein is a virion structural protein. It also functions, however, in an unknown way in viral replication and localizes to the viral replication-transcription complexes (RTCs). Here we investigated, using recombinant murine coronaviruses expressing green fluorescent protein (GFP)-tagged versions of the N protein, the dynamics of its interactions with the RTCs and the domain(s) involved. Using fluorescent recovery after photobleaching, we showed that the N protein, unlike the nonstructural protein 2, is dynamically associated with the RTCs. Recruitment of the N protein to the RTCs requires the C-terminal N2b domain, which interacts with other N proteins in an RNA-independent manner.",,"['Verheije, Monique H.', 'Hagemeijer, Marne C.', 'Ulasli, Mustafa', 'Reggiori, Fulvio', 'Rottier, Peter J. M.', 'Masters, Paul S.', 'Haan, Cornelis A. M. de']",,,,
,PMC,Murine Coronavirus Receptors Are Differentially Expressed in the Central Nervous System and Play Virus Strain-Dependent Roles in Neuronal Spread,http://dx.doi.org/10.1128/JVI.02688-09,PMC2953140,,,"Coronavirus infection of the murine central nervous system (CNS) provides a model for studies of viral encephalitis and demyelinating disease. Mouse hepatitis virus (MHV) neurotropism varies by strain: MHV-A59 causes mild encephalomyelitis and demyelination, while the highly neurovirulent strain JHM.SD (MHV-4) causes fatal encephalitis with extensive neuronal spread of virus. In addition, while neurons are the predominant CNS cell type infected in vivo, the canonical receptor for MHV, the carcinoembryonic antigen family member CEACAM1a, has been demonstrated only on endothelial cells and microglia. In order to investigate whether CEACAM1a is also expressed in other cell types, ceacam1a mRNA expression was quantified in murine tissues and primary cells. As expected, among CNS cell types, microglia expressed the highest levels of ceacam1a, but lower levels were also detected in oligodendrocytes, astrocytes, and neurons. Given the low levels of neuronal expression of ceacam1a, primary neurons from wild-type and ceacam1a knockout mice were inoculated with MHV to determine the extent to which CEACAM1a-independent infection might contribute to CNS infection. While both A59 and JHM.SD infected small numbers of ceacam1a knockout neurons, only JHM.SD spread efficiently to adjacent cells in the absence of CEACAM1a. Quantification of mRNA for the ceacam1a-related genes ceacam2 and psg16 (bCEA), which encode proposed alternative MHV receptors, revealed low ceacam2 expression in microglia and oligodendrocytes and psg16 expression exclusively in neurons; however, only CEACAM2 mediated infection in human 293T cells. Therefore, neither CEACAM2 nor PSG16 is likely to be an MHV receptor on neurons, and the mechanism for CEACAM1a-independent neuronal spread of JHM.SD remains unknown.",,"['Bender, Susan J.', 'Phillips, Judith M.', 'Scott, Erin P.', 'Weiss, Susan R.']",,,,
,PMC,The Rate of Hepatitis C Virus Infection Initiation in vitro is Directly Related to Particle Density,http://dx.doi.org/10.1016/j.virol.2010.07.026,PMC2946418,,,"To gain a more complete understanding of hepatitis C virus (HCV) entry, we initially assessed the rate at which HCV initiates productive attachment/infection in vitro and discovered it to be slower than most viruses. Since HCV, including cell culture-derived HCV (HCVcc), exhibits a broad density profile (1.01 – 1.16 g/ml), we hypothesized that the varying densities of the HCVcc particles present in the inoculum may be responsible for this prolonged entry phenotype. To test this hypothesis, we show that during infection, particles of high-density disappeared from the viral inoculum sooner and initiated productive infection faster than virions of low-density. Moreover, we could alter the rate of attachment/infection initiation by increasing or decreasing the density of the cell culture medium. Together, these findings demonstrate that the relationship between the density of HCVcc and the density of the extracellular milieu can significantly impact the rate at which HCVcc productively interacts with target cells in vitro.",,"['Sabahi, Ali', 'Marsh, Katherine A.', 'Dahari, Harel', 'Corcoran, Peter', 'Lamora, Jennifer M.', 'Yu, Xuemei', 'Garry, Robert F.', 'Uprichard, Susan L.']",,,,
,PMC,A SUMO-GROUCHO Q DOMAIN FUSION PROTEIN: CHARACTERIZATION AND IN VIVO ULP1-MEDIATED CLEAVAGE,http://dx.doi.org/10.1016/j.pep.2010.08.008,PMC3005967,,,"We describe here a system for the expression and purification of small ubiquitin-related modifier (SUMO) fusion proteins, which often exhibit dramatically increased solubility and stability during expression in bacteria relative to unfused proteins. The vector described here allows expression of a His-tagged protein of interest fused at its N-terminus to SUMO. Using this vector, we have produced a polypeptide consisting of SUMO fused to the Q-domain of Drosophila Groucho in a concentrated soluble form. Hydrodynamic analysis shows that, consistent with previous studies on full-length Groucho, the fusion protein forms an elongated tetramer, as well as higher order oligomers. After expressing a protein as a fusion to SUMO, it is often desirable to cleave the SUMO off of the fusion protein using a SUMO-specific protease such as Ulp1. To facilitate such processing, we have constructed a dual expression vector encoding two fusion proteins: one consisting of SUMO fused to Ulp1 and a second consisting of SUMO fused to a His-tagged protein of interest. The SUMO-Ulp1 cleaves both itself and the other SUMO fusion protein in the bacterial cells prior to lysis, and the proteins retain solubility after cleavage.",,"['Kuo, Dennis', 'Nie, Minghua', 'De Hoff, Peter', 'Chambers, Michael', 'Phillips, Martin', 'Hirsch, Ann M.', 'Courey, Albert J.']",,,,
,PMC,Yeast Proteomics and Protein Microarrays,http://dx.doi.org/10.1016/j.jprot.2010.08.003,PMC2949546,,,"Our understanding of biological processes as well as human diseases has improved greatly thanks to studies on model organisms such as yeast. The power of scientific approaches with yeast lies in its relatively simple genome, its facile classical and molecular genetics, as well as the evolutionary conservation of many basic biological mechanisms. However, even in this simple model organism, systems biology studies, especially proteomic studies had been an intimidating task. During the past decade, powerful high-throughput technologies in proteomic research have been developed for yeast including protein microarray technology. The protein microarray technology allows the interrogation of protein-protein, protein-DNA, protein-small molecule interaction networks as well as post-translational modification networks in a large-scale, high-throughput manner. With this technology, many groundbreaking findings have been established in studies with the budding yeast Saccharomyces cerevisiae, most of which could have been unachievable with traditional approaches. Discovery of these networks has profound impact on explicating biological processes with a proteomic point of view, which may lead to a better understanding of normal biological phenomena as well as various human diseases.",,"['Chen, Rui', 'Snyder, Michael']",,,,
,PMC,A Conserved Domain in the Coronavirus Membrane Protein Tail Is Important for Virus Assembly,http://dx.doi.org/10.1128/JVI.01131-10,PMC2953170,,,"Coronavirus membrane (M) proteins play key roles in virus assembly, through M-M, M-spike (S), and M-nucleocapsid (N) protein interactions. The M carboxy-terminal endodomain contains a conserved domain (CD) following the third transmembrane (TM) domain. The importance of the CD (SWWSFNPETNNL) in mouse hepatitis virus was investigated with a panel of mutant proteins, using genetic analysis and transient-expression assays. A charge reversal for negatively charged E(121) was not tolerated. Lysine (K) and arginine (R) substitutions were replaced in recovered viruses by neutrally charged glutamine (Q) and leucine (L), respectively, after only one passage. E(121)Q and E(121)L M proteins were capable of forming virus-like particles (VLPs) when coexpressed with E, whereas E(121)R and E(121)K proteins were not. Alanine substitutions for the first four or the last four residues resulted in viruses with significantly crippled phenotypes and proteins that failed to assemble VLPs or to be rescued into the envelope. All recovered viruses with alanine substitutions in place of SWWS residues had second-site, partially compensating, changes in the first TM of M. Alanine substitution for proline had little impact on the virus. N protein coexpression with some M mutants increased VLP production. The results overall suggest that the CD is important for formation of the viral envelope by helping mediate fundamental M-M interactions and that the presence of the N protein may help stabilize M complexes during virus assembly.",,"['Arndt, Ariel L.', 'Larson, Blake J.', 'Hogue, Brenda G.']",,,,
,PMC,Design of a Potent d-Peptide HIV-1 Entry Inhibitor with a Strong Barrier to Resistance,http://dx.doi.org/10.1128/JVI.01339-10,PMC2953169,,,"The HIV gp41 N-trimer pocket region is an ideal viral target because it is extracellular, highly conserved, and essential for viral entry. Here, we report on the design of a pocket-specific d-peptide, PIE12-trimer, that is extraordinarily elusive to resistance and characterize its inhibitory and structural properties. d-Peptides (peptides composed of d-amino acids) are promising therapeutic agents due to their insensitivity to protease degradation. PIE12-trimer was designed using structure-guided mirror-image phage display and linker optimization and is the first d-peptide HIV entry inhibitor with the breadth and potency required for clinical use. PIE12-trimer has an ultrahigh affinity for the gp41 pocket, providing it with a reserve of binding energy (resistance capacitor) that yields a dramatically improved resistance profile compared to those of other fusion inhibitors. These results demonstrate that the gp41 pocket is an ideal drug target and establish PIE12-trimer as a leading anti-HIV antiviral candidate.",,"['Welch, Brett D.', 'Francis, J. Nicholas', 'Redman, Joseph S.', 'Paul, Suparna', 'Weinstock, Matthew T.', 'Reeves, Jacqueline D.', 'Lie, Yolanda S.', 'Whitby, Frank G.', 'Eckert, Debra M.', 'Hill, Christopher P.', 'Root, Michael J.', 'Kay, Michael S.']",,,,
,PMC,"Culturing the Unculturable: Human Coronavirus HKU1 Infects, Replicates, and Produces Progeny Virions in Human Ciliated Airway Epithelial Cell Cultures",http://dx.doi.org/10.1128/JVI.00947-10,PMC2953148,,,"Culturing newly identified human lung pathogens from clinical sample isolates can represent a daunting task, with problems ranging from low levels of pathogens to the presence of growth suppressive factors in the specimens, compounded by the lack of a suitable tissue culture system. However, it is critical to develop suitable in vitro platforms to isolate and characterize the replication kinetics and pathogenesis of recently identified human pathogens. HCoV-HKU1, a human coronavirus identified in a clinical sample from a patient with severe pneumonia, has been a major challenge for successful propagation on all immortalized cells tested to date. To determine if HCoV-HKU1 could replicate in in vitro models of human ciliated airway epithelial cell cultures (HAE) that recapitulate the morphology, biochemistry, and physiology of the human airway epithelium, the apical surfaces of HAE were inoculated with a clinical sample of HCoV-HKU1 (Cean1 strain). High virus yields were found for several days postinoculation and electron micrograph, Northern blot, and immunofluorescence data confirmed that HCoV-HKU1 replicated efficiently within ciliated cells, demonstrating that this cell type is infected by all human coronaviruses identified to date. Antiserum directed against human leukocyte antigen C (HLA-C) failed to attenuate HCoV-HKU1 infection and replication in HAE, suggesting that HLA-C is not required for HCoV-HKU1 infection of the human ciliated airway epithelium. We propose that the HAE model provides a ready platform for molecular studies and characterization of HCoV-HKU1 and in general serves as a robust technology for the recovery, amplification, adaptation, and characterization of novel coronaviruses and other respiratory viruses from clinical material.",,"['Pyrc, Krzysztof', 'Sims, Amy C.', 'Dijkman, Ronald', 'Jebbink, Maarten', 'Long, Casey', 'Deming, Damon', 'Donaldson, Eric', 'Vabret, Astrid', 'Baric, Ralph', 'van der Hoek, Lia', 'Pickles, Raymond']",,,,
,PMC,"Characterization of hMTr1, a Human Cap1 2′-O-Ribose Methyltransferase",http://dx.doi.org/10.1074/jbc.M110.155283,PMC2963352,,,"Cellular eukaryotic mRNAs are capped at their 5′ ends with a 7-methylguanosine nucleotide, a structural feature that has been shown to be important for conferring mRNA stability, stimulating mRNA biogenesis (splicing, poly(A) addition, nucleocytoplasmic transport), and increasing translational efficiency. Whereas yeast mRNAs have no additional modifications to the cap, called cap0, higher eukaryotes are methylated at the 2′-O-ribose of the first or the first and second transcribed nucleotides, called cap1 and cap2, respectively. In the present study, we identify the methyltransferase responsible for cap1 formation in human cells, which we call hMTr1 (also known as FTSJD2 and ISG95). We show in vitro that hMTr1 catalyzes specific methylation of the 2′-O-ribose of the first nucleotide of a capped RNA transcript. Using siRNA-mediated knockdown of hMTr1 in HeLa cells, we demonstrate that hMTr1 is responsible for cap1 formation in vivo.",,"['Bélanger, François', 'Stepinski, Janusz', 'Darzynkiewicz, Edward', 'Pelletier, Jerry']",,,,
,PMC,Mortality patterns associated with the 1918 influenza pandemic in Mexico: evidence for a spring herald wave and lack of pre-existing immunity in older populations,http://dx.doi.org/10.1086/654897,PMC2945372,,,"BACKGROUND: While the mortality burden of the devastating 1918 influenza pandemic has been carefully quantified in the US, Japan, and European countries, little is known about the pandemic experience elsewhere. Here, we compiled extensive archival records to quantify the pandemic mortality patterns in two Mexican cities, Mexico City and Toluca. METHODS: We applied seasonal excess mortality models to age-specific respiratory mortality rates for 1915–1920 and quantified the reproduction number from daily data. RESULTS: We identified 3 pandemic waves in Mexico City in spring 1918, fall 1918, and winter 1920, characterized by unusual excess mortality in 25–44 years old. Toluca experienced 2-fold higher excess mortality rates than Mexico City, but did not have a substantial 3(rd) wave. All age groups including those over 65 years experienced excess mortality during 1918–20. Reproduction number estimates were below 2.5 assuming a 3-day generation interval. CONCLUSION: Mexico experienced a herald pandemic wave with elevated young adult mortality in spring 1918, similar to the US and Europe. In contrast to the US and Europe, there was no mortality sparing in Mexican seniors, highlighting potential geographical differences in pre-existing immunity to the 1918 virus. We discuss the relevance of our findings to the 2009 pandemic mortality patterns.",,"['Chowell, Gerardo', 'Viboud, Cécile', 'Simonsen, Lone', 'Miller, Mark A.', 'Acuna-Soto, Rodolfo']",,,,
,PMC,Feline models of viral pathogenesis: Opportunity knocks,http://dx.doi.org/10.1016/j.tvjl.2010.07.013,PMC2988874,,,,,"['Troyer, Jennifer L.', 'Brown, Meredith A.']",,,,
,PMC,NMR Structure of the SARS Coronavirus Nonstructural Protein 7 in Solution at pH 6.5,http://dx.doi.org/10.1016/j.jmb.2010.07.043,PMC3081601,,,"The NMR structure of the severe acute respiratory syndrome coronavirus (SARS-CoV) non-structural protein 7 (nsp7) in aqueous solution at pH 6.5 was determined and compared with the results of previous structure determinations of nsp7 in solution at pH 7.5 and in crystals of a hexadecameric nsp7/nsp8 complex obtained from a solution at pH 7.5. All three structures contain four helices as the only regular secondary structures, but there are differences in the lengths and sequence locations of the four helices, as well as between the tertiary folds. The present study includes data on conformational equilibria and intramolecular rate processes in nsp7 in solution at pH 6.5, which provides further insights into the polymorphisms implicated by comparison of the presently available three nsp7 structures.",,"['Johnson, Margaret A.', 'Jaudzems, Kristaps', 'Wüthrich, Kurt']",,,,
,PMC,"Generation of VSV Pseudotypes Using Recombinant ΔG-VSV for Studies on Virus Entry, Identification of Entry Inhibitors, and Immune Responses to Vaccines",http://dx.doi.org/10.1016/j.jviromet.2010.08.006,PMC2956192,,,"Vesicular stomatitis virus (VSV) is a prototypic enveloped animal virus that has been used extensively to study virus entry, replication and assembly due to its broad host range and robust replication properties in a wide variety of mammalian and insect cells. Studies on VSV assembly led to the creation of a recombinant VSV in which the glycoprotein (G) gene was deleted. This recombinant (rVSV-ΔG) has been used to produce VSV pseudotypes containing the envelope glycoproteins of heterologous viruses, including viruses that require high-level biocontainment; however, because the infectivity of rVSV-ΔG pseudotypes is restricted to a single round of replication the analysis can be performed using biosafety level 2 (BSL-2) containment. As such, rVSV-ΔG pseudotypes have facilitated the analysis of virus entry for numerous viral pathogens without the need for specialized containment facilities. The pseudotypes also provide a robust platform to screen libraries for entry inhibitors and to evaluate the neutralizing antibody responses following vaccination. This manuscript describes methods to produce and titer rVSV-ΔG pseudotypes. Procedures to generate rVSV-ΔG stocks and to quantify virus infectivity are also described. These protocols should allow any laboratory knowledgeable in general virological and cell culture techniques to produce successfully replication-restricted rVSV-ΔG pseudotypes for subsequent analysis.",,"Whitt, Michael A.",,,,
,PMC,Purification and characterization of HIV–human protein complexes,http://dx.doi.org/10.1016/j.ymeth.2010.08.007,PMC3076283,,,"To fully understand how pathogens infect their host and hijack key biological processes, systematic mapping of intra-pathogenic and pathogen–host protein–protein interactions (PPIs) is crucial. Due to the relatively small size of viral genomes (usually around 10–100 proteins), generation of comprehensive host–virus PPI maps using different experimental platforms, including affinity tag purification-mass spectrometry (AP-MS) and yeast two-hybrid (Y2H) approaches, can be achieved. Global maps such as these provide unbiased insight into the molecular mechanisms of viral entry, replication and assembly. However, to date, only two-hybrid methodology has been used in a systematic fashion to characterize viral–host protein–protein interactions, although a deluge of data exists in databases that manually curate from the literature individual host–pathogen PPIs. We will summarize this work and also describe an AP-MS platform that can be used to characterize viral-human protein complexes and discuss its application for the HIV genome.",,"['Jäger, Stefanie', 'Gulbahce, Natali', 'Cimermancic, Peter', 'Kane, Joshua', 'He, Nanhai', 'Chou, Seemay', 'D’Orso, Iván', 'Fernandes, Jason', 'Jang, Gwendolyn', 'Frankel, Alan D.', 'Alber, Tom', 'Zhou, Qiang', 'Krogan, Nevan J.']",,,,
,PMC,MTA1 Coregulator Regulates LPS Response via MyD88-dependent Signaling,http://dx.doi.org/10.1074/jbc.M110.151340,PMC2963354,,,"Although metastasis tumor antigen 1 (MTA1) contributes to the responsiveness of macrophages to LPS, the underlying mechanism remains unknown. Here, we investigated the role of MTA1 in the regulation of expression and function of MyD88, a proximal component of NF-κB signaling. We discovered that MTA1 targets MyD88 and that MyD88 is a NF-κB-responsive gene in LPS-stimulated macrophages. We found that MTA1 is required for MyD88-dependent stimulation of NF-κB signaling and expression of proinflammatory cytokines such as IL-1β, MIP2, and TNF-α as MTA1 depletion leads to a substantial reduction in the expression of NF-κB target genes. In addition, LPS-mediated stimulation of MyD88 transcription was accompanied by an enhanced recruitment of MTA1, RNA polymerase II, and p65RelA complex to the NF-κB consensus sites in the MyD88 promoter. Interestingly, the recruitment of both MTA1 and MyD88 expression is effectively blocked by NF-κB inhibitor parthenolide. Selective knockdown of MyD88 by a dominant negative mutant of MyD88 or selective siRNA also impairs the ability of LPS to stimulate the NF-κB target genes. These findings reveal an inherent coregulatory role of MTA1 upon the expression of MyD88 and suggest that MTA1 regulation of MyD88 may constitute at least one of the mechanisms by which MTA1 stimulates LPS-induced NF-κB signaling in stimulated macrophages.",,"['Pakala, Suresh B.', 'Reddy, Sirigiri Divijendra Natha', 'Bui-Nguyen, Tri M.', 'Rangparia, Siddharth S.', 'Bommana, Anitha', 'Kumar, Rakesh']",,,,
,PMC,Comparison of Combined Nose-Throat Swabs with Nasopharyngeal Aspirates for Detection of Pandemic Influenza A/H1N1 2009 Virus by Real-Time Reverse Transcriptase PCR,http://dx.doi.org/10.1128/JCM.01105-10,PMC2953095,,,"Data assessing the diagnostic accuracies of use of different respiratory samples for the detection of the novel influenza A/H1N1 2009 virus by molecular methods are lacking. The objective of this study was to compare the sensitivity of combined nose and throat swabs (CNTS) with that of nasopharyngeal aspirates (NPA). This was a prospective study of adults and children with suspected influenza. Real-time reverse transcriptase PCR testing was used for the virological diagnosis. Of the 2,473 patients included, 264 with paired CNTS and NPA were randomly selected. Novel influenza A/H1N1 virus was identified in at least one sample for 115 (43.6%) patients, the majority of them young adults. In 109 patients (94.8%) the virus was identified in the CNTS, and in 98 (85.2%) it was identified in the NPA (P = 0.02). In 93 patients (80.1%), the virus was identified in both specimens. Spearman's rho correlation coefficient between the two methods was 0.82 (P < 0.001). There were no significant differences in accuracy between the specimens when patients were stratified according to demographic or clinical characteristics except in the case of women, in whom the sensitivity of CNTS was higher (P = 0.01). The combination of CNTS and NPA had a significantly higher sensitivity in identifying the virus than did each method alone (P = 0.02 for the comparison of the combination of both sampling methods with CNTS, and P < 0.001 for the comparison with NPA). We conclude that in patients with the novel influenza A/H1N1 virus, the diagnostic yield of CNTS is higher than that of NPA. The combination of both sampling methods increases the likelihood of diagnosing the virus.",,"['Ortiz de la Tabla, Victoria', 'Masiá, Mar', 'Antequera, Pedro', 'Martin, Coral', 'Gazquez, Gregoria', 'Buñuel, Fernando', 'Gutiérrez, Félix']",,,,
,PMC,Toll-Like Receptor 4-Mediated Activation of p38 Mitogen-Activated Protein Kinase Is a Determinant of Respiratory Virus Entry and Tropism,http://dx.doi.org/10.1128/JVI.00804-10,PMC2953195,,,"Respiratory viruses exert a heavy toll of morbidity and mortality worldwide. Despite this burden there are few specific treatments available for respiratory virus infections. Since many viruses utilize host cell enzymatic machinery such as protein kinases for replication, we determined whether pharmacological inhibition of kinases could, in principle, be used as a broad antiviral strategy for common human respiratory virus infections. A panel of green fluorescent protein (GFP)-expressing recombinant respiratory viruses, including an isolate of H1N1 influenza virus (H1N1/Weiss/43), was used to represent a broad range of virus families responsible for common respiratory infections (Adenoviridae, Paramyxoviridae, Picornaviridae, and Orthomyxoviridae). Kinase inhibitors were screened in a high-throughput assay that detected virus infection in human airway epithelial cells (1HAEo-) using a fluorescent plate reader. Inhibition of p38 mitogen-activated protein kinase (MAPK) signaling was able to significantly inhibit replication by all viruses tested. Therefore, the pathways involved in virus-mediated p38 and extracellular signal-regulated kinase (ERK) MAPK activation were investigated using bronchial epithelial cells and primary fibroblasts derived from MyD88 knockout mouse lungs. Influenza virus, which activated p38 MAPK to approximately 10-fold-greater levels than did respiratory syncytial virus (RSV) in 1HAEo- cells, was internalized about 8-fold faster and more completely than RSV. We show for the first time that p38 MAPK is a determinant of virus infection that is dependent upon MyD88 expression and Toll-like receptor 4 (TLR4) ligation. Imaging of virus-TLR4 interactions showed significant clustering of TLR4 at the site of virus-cell interaction, triggering phosphorylation of downstream targets of p38 MAPK, suggesting the need for a signaling receptor to activate virus internalization.",,"['Marchant, David', 'Singhera, Gurpreet K.', 'Utokaparch, Soraya', 'Hackett, Tillie L.', 'Boyd, John H.', 'Luo, Zongshu', 'Si, Xiaoning', 'Dorscheid, Delbert R.', 'McManus, Bruce M.', 'Hegele, Richard G.']",,,,
,PMC,Transcriptomic Analysis Reveals a Mechanism for a Prefibrotic Phenotype in STAT1 Knockout Mice during Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/JVI.01130-10,PMC2953159,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) infection can cause the development of severe end-stage lung disease characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. The mechanisms by which pulmonary lesions and fibrosis are generated during SARS-CoV infection are not known. Using high-throughput mRNA profiling, we examined the transcriptional response of wild-type (WT), type I interferon receptor knockout (IFNAR1(−/−)), and STAT1 knockout (STAT1(−/−)) mice infected with a recombinant mouse-adapted SARS-CoV (rMA15) to better understand the contribution of specific gene expression changes to disease progression. Despite a deletion of the type I interferon receptor, strong expression of interferon-stimulated genes was observed in the lungs of IFNAR1(−/−) mice, contributing to clearance of the virus. In contrast, STAT1(−/−) mice exhibited a defect in the expression of interferon-stimulated genes and were unable to clear the infection, resulting in a lethal outcome. STAT1(−/−) mice exhibited dysregulation of T-cell and macrophage differentiation, leading to a T(H)2-biased immune response and the development of alternatively activated macrophages that mediate a profibrotic environment within the lung. We propose that a combination of impaired viral clearance and T-cell/macrophage dysregulation causes the formation of prefibrotic lesions in the lungs of rMA15-infected STAT1(−/−) mice.",,"['Zornetzer, Gregory A.', 'Frieman, Matthew B.', 'Rosenzweig, Elizabeth', 'Korth, Marcus J.', 'Page, Carly', 'Baric, Ralph S.', 'Katze, Michael G.']",,,,
,PMC,Coexistence of Different Genotypes in the Same Bat and Serological Characterization of Rousettus Bat Coronavirus HKU9 Belonging to a Novel Betacoronavirus Subgroup,http://dx.doi.org/10.1128/JVI.01121-10,PMC2953156,,,"Rousettus bat coronavirus HKU9 (Ro-BatCoV HKU9), a recently identified coronavirus of novel Betacoronavirus subgroup D, from Leschenault's rousette, was previously found to display marked sequence polymorphism among genomes of four strains. Among 10 bats with complete RNA-dependent RNA polymerase (RdRp), spike (S), and nucleocapsid (N) genes sequenced, three and two sequence clades for all three genes were codetected in two and five bats, respectively, suggesting the coexistence of two or three distinct genotypes of Ro-BatCoV HKU9 in the same bat. Complete genome sequencing of the distinct genotypes from two bats, using degenerate/genome-specific primers with overlapping sequences confirmed by specific PCR, supported the coexistence of at least two distinct genomes in each bat. Recombination analysis using eight Ro-BatCoV HKU9 genomes showed possible recombination events between strains from different bat individuals, which may have allowed for the generation of different genotypes. Western blot assays using recombinant N proteins of Ro-BatCoV HKU9, Betacoronavirus subgroup A (HCoV-HKU1), subgroup B (SARSr-Rh-BatCoV), and subgroup C (Ty-BatCoV HKU4 and Pi-BatCoV HKU5) coronaviruses were subgroup specific, supporting their classification as separate subgroups under Betacoronavirus. Antibodies were detected in 75 (43%) of 175 and 224 (64%) of 350 tested serum samples from Leschenault's rousette bats by Ro-BatCoV HKU9 N-protein-based Western blot and enzyme immunoassays, respectively. This is the first report describing coinfection of different coronavirus genotypes in bats and coronavirus genotypes of diverse nucleotide variation in the same host. Such unique phenomena, and the unusual instability of ORF7a, are likely due to recombination which may have been facilitated by the dense roosting behavior and long foraging range of Leschenault's rousette.",,"['Lau, Susanna K. P.', 'Poon, Rosana W. S.', 'Wong, Beatrice H. L.', 'Wang, Ming', 'Huang, Yi', 'Xu, Huifang', 'Guo, Rongtong', 'Li, Kenneth S. M.', 'Gao, Kai', 'Chan, Kwok-Hung', 'Zheng, Bo-Jian', 'Woo, Patrick C. Y.', 'Yuen, Kwok-Yung']",,,,
,PMC,Molecular Mapping of the RNA Cap 2′-O-Methyltransferase Activation Interface between Severe Acute Respiratory Syndrome Coronavirus nsp10 and nsp16,http://dx.doi.org/10.1074/jbc.M110.120014,PMC2963367,,,"Several protein-protein interactions within the SARS-CoV proteome have been identified, one of them being between non-structural proteins nsp10 and nsp16. In this work, we have mapped key residues on the nsp10 surface involved in this interaction. Alanine-scanning mutagenesis, bioinformatics, and molecular modeling were used to identify several “hot spots,” such as Val(42), Met(44), Ala(71), Lys(93), Gly(94), and Tyr(96), forming a continuous protein-protein surface of about 830 Å(2), bearing very conserved amino acids among coronaviruses. Because nsp16 carries RNA cap 2′-O-methyltransferase (2′O-MTase) activity only in the presence of its interacting partner nsp10 (Bouvet, M., Debarnot, C., Imbert, I., Selisko, B., Snijder, E. J., Canard, B., and Decroly, E. (2010) PLoS Pathog. 6, e1000863), functional consequences of mutations on this surface were evaluated biochemically. Most changes that disrupted the nsp10-nsp16 interaction without structural perturbations were shown to abrogate stimulation of nsp16 RNA cap 2′O-MTase activity. More strikingly, the Y96A mutation abrogates stimulation of nsp16 2′O-MTase activity, whereas Y96F overstimulates it. Thus, the nsp10-nsp16 interface may represent an attractive target for antivirals against human and animal pathogenic coronaviruses.",,"['Lugari, Adrien', 'Betzi, Stephane', 'Decroly, Etienne', 'Bonnaud, Emmanuel', 'Hermant, Aurélie', 'Guillemot, Jean-Claude', 'Debarnot, Claire', 'Borg, Jean-Paul', 'Bouvet, Mickaël', 'Canard, Bruno', 'Morelli, Xavier', 'Lécine, Patrick']",,,,
,PMC,Functional Rescue of Dystrophin-deficient mdx Mice by a Chimeric Peptide-PMO,http://dx.doi.org/10.1038/mt.2010.151,PMC2951563,,,"Splice modulation using antisense oligonucleotides (AOs) has been shown to yield targeted exon exclusion to restore the open reading frame and generate truncated but partially functional dystrophin protein. This has been successfully demonstrated in dystrophin-deficient mdx mice and in Duchenne muscular dystrophy (DMD) patients. However, DMD is a systemic disease; successful therapeutic exploitation of this approach will therefore depend on effective systemic delivery of AOs to all affected tissues. We have previously shown the potential of a muscle-specific/arginine-rich chimeric peptide-phosphorodiamidate morpholino (PMO) conjugate, but its long-term activity, optimized dosing regimen, capacity for functional correction and safety profile remain to be established. Here, we report the results of this chimeric peptide-PMO conjugate in the mdx mouse using low doses (3 and 6 mg/kg) administered via a 6 biweekly systemic intravenous injection protocol. We show 100% dystrophin-positive fibers and near complete correction of the dystrophin transcript defect in all peripheral muscle groups, with restoration of 50% dystrophin protein over 12 weeks, leading to correction of the DMD pathological phenotype and restoration of muscle function in the absence of detectable toxicity or immune response. Chimeric muscle-specific/cell-penetrating peptides therefore represent highly promising agents for systemic delivery of splice-correcting PMO oligomers for DMD therapy.",,"['Yin, HaiFang', 'Moulton, Hong M', 'Betts, Corinne', 'Merritt, Thomas', 'Seow, Yiqi', 'Ashraf, Shirin', 'Wang, QingSong', 'Boutilier, Jordan', 'Wood, Matthew JA']",,,,
,PMC,Roles of the respiratory syncytial virus trailer region: Effects of mutations on genome production and stress granule formation,http://dx.doi.org/10.1016/j.virol.2010.07.006,PMC2971657,,,"The 5′ extragenic trailer region of respiratory syncytial virus (RSV) is known to be necessary for genome replication, but is more than three times the length of the 3′ leader replication promoter, raising the possibility that trailer might play an additional role in viral replication. To examine this, mutant recombinant viruses were constructed in which the trailer region was truncated or substituted with leader-complement sequence. This analysis showed that the complete trailer increased promoter activity, facilitating genome production and viral multiplication. In addition, trailer-containing viruses did not induce stress granules, whereas the leader-complement virus mutant did, resulting in poor multi-cycle viral growth. These data demonstrate that although the RSV trailer does not contain a unique essential sequence, it augments virus growth by enabling optimal genome production. In addition, a sequence at the 5′ terminal end of the trailer region allows RSV to subvert stress granule formation.",,"['Hanley, Laura L.', 'McGivern, David R.', 'Teng, Michael N.', 'Djang, Robin', 'Collins, Peter L.', 'Fearns, Rachel']",,,,
,PMC,Platform technology to deliver prophylactic molecules orally: an example using the Class A select agent Yersinia pestis,http://dx.doi.org/10.1016/j.vaccine.2010.07.084,PMC2942074,,,,,"['del Rio, Beatriz', 'Fuente, Jesus Lajara', 'Neves, Vera', 'Dattwyler, Raymond', 'Seegers, Jos F.M.L.', 'Gomes-Solecki, Maria']",,,,
,PMC,Association between human rhinovirus C and severity of acute asthma in children,http://dx.doi.org/10.1183/09031936.00092410,PMC3024467,,,"BACKGROUND: A new and potentially more pathogenic group of human rhinoviruses (HRV), group C (HRVC) has recently been discovered. We hypothesised that HRVC would be present in children with acute asthma and cause more severe attacks than other viruses or HRV groups. METHODS: Children with acute asthma (n=128, 2–16 years) were recruited on presentation to an emergency department. Asthma exacerbation severity was assessed and respiratory viruses and HRV strains were identified in a nasal aspirate. RESULTS: The majority of the children studied had moderate to severe asthma (85.2%) and 98.9% were admitted to hospital. HRV was detected in 87.5% and other respiratory viruses in 14.8% of children, most of whom also had HRV. HRVC were present in the majority of children with acute asthma (59.4%) and associated with more severe asthma. Children with HRVC (n=76) had higher asthma severity scores than children whose HRV infection was HRVA or HRVB only (n=34, p=0.018), and all other children (n=50, p=0.016). Of 19 children with a non-HRV virus, 13 had HRV co-infections, seven of these being HRVC. CONCLUSION: HRVC accounts for the majority of asthma attacks in children presenting to hospital and causes more severe attacks than previously-known HRV groups and other viruses.",,"['Bizzintino, J', 'Lee, W-M', 'Laing, IA', 'Vang, F', 'Pappas, T', 'Zhang, G', 'Martin, AC', 'Geelhoed, GC', 'McMinn, PC', 'Goldblatt, J', 'Gern, JE', 'Le Souëf, PN']",,,,
,PMC,"Rift Valley Fever Virus Epidemic in Kenya, 2006/2007: The Entomologic Investigations",http://dx.doi.org/10.4269/ajtmh.2010.09-0319,PMC2913497,,,"In December 2006, Rift Valley fever (RVF) was diagnosed in humans in Garissa Hospital, Kenya and an outbreak reported affecting 11 districts. Entomologic surveillance was performed in four districts to determine the epidemic/epizootic vectors of RVF virus (RVFV). Approximately 297,000 mosquitoes were collected, 164,626 identified to species, 72,058 sorted into 3,003 pools and tested for RVFV by reverse transcription-polymerase chain reaction. Seventy-seven pools representing 10 species tested positive for RVFV, including Aedes mcintoshi/circumluteolus (26 pools), Aedes ochraceus (23 pools), Mansonia uniformis (15 pools); Culex poicilipes, Culex bitaeniorhynchus (3 pools each); Anopheles squamosus, Mansonia africana (2 pools each); Culex quinquefasciatus, Culex univittatus, Aedes pembaensis (1 pool each). Positive Ae. pembaensis, Cx. univittatus, and Cx. bitaeniorhynchus was a first time observation. Species composition, densities, and infection varied among districts supporting hypothesis that different mosquito species serve as epizootic/epidemic vectors of RVFV in diverse ecologies, creating a complex epidemiologic pattern in East Africa.",,"['Sang, Rosemary', 'Kioko, Elizabeth', 'Lutomiah, Joel', 'Warigia, Marion', 'Ochieng, Caroline', ""O'Guinn, Monica"", 'Lee, John S.', 'Koka, Hellen', 'Godsey, Marvin', 'Hoel, David', 'Hanafi, Hanafi', 'Miller, Barry', 'Schnabel, David', 'Breiman, Robert F.', 'Richardson, Jason']",,,,
,PMC,Rift Valley Fever: Scientific Pathways Toward Public Health Prevention and Response,http://dx.doi.org/10.4269/ajtmh.2010.83s2a01,PMC2913493,,,,,"['Breiman, Robert F.', 'Minjauw, Bruno', 'Sharif, S. K.', 'Ithondeka, Peter', 'Njenga, M. Kariuki']",,,,
,PMC,Biochip System for Rapid and Accurate Identification of Mycobacterial Species from Isolates and Sputum,http://dx.doi.org/10.1128/JCM.00158-10,PMC2953089,,,"The accurate detection of mycobacterial species from isolates and clinical samples is important for pathogenic diagnosis and treatment and for disease control. There is an urgent need for the development of a rapid, simple, and accurate detection method. We established a biochip assay system, including a biochip, sample preparation apparatus, hybridization instrument, chip washing machine, and laser confocal scanner equipped with interpretation software for automatic diagnosis. The biochip simultaneously identified 17 common mycobacterial species by targeting the differences in the 16S rRNA. The system was assessed with 64 reference strains and 296 Mycobacterium tuberculosis and 243 nontuberculous mycobacterial isolates, as well as 138 other bacteria and 195 sputum samples, and then compared to DNA sequencing. The entire biochip assay took 6 h. The concordance rate between the biochip assay and the DNA sequencing results was 100%. In conclusion, the biochip system provides a simple, rapid, reliable, and highly accurate clinical assay for determination of mycobacterial species in a 6-h procedure, from either culture isolates or sputum samples, allowing earlier pathogen-adapted antimicrobial therapy in patients.",,"['Zhu, Lingxiang', 'Jiang, Guanglu', 'Wang, Shengfen', 'Wang, Can', 'Li, Qiang', 'Yu, Hao', 'Zhou, Yang', 'Zhao, Bing', 'Huang, Hairong', 'Xing, Wanli', 'Mitchelson, Keith', 'Cheng, Jing', 'Zhao, Yanlin', 'Guo, Yong']",,,,
,PMC,Genomic Characterization of Severe Acute Respiratory Syndrome-Related Coronavirus in European Bats and Classification of Coronaviruses Based on Partial RNA-Dependent RNA Polymerase Gene Sequences,http://dx.doi.org/10.1128/JVI.00650-10,PMC2953168,,,"Bats may host emerging viruses, including coronaviruses (CoV). We conducted an evaluation of CoV in rhinolophid and vespertilionid bat species common in Europe. Rhinolophids carried severe acute respiratory syndrome (SARS)-related CoV at high frequencies and concentrations (26% of animals are positive; up to 2.4 × 10(8) copies per gram of feces), as well as two Alphacoronavirus clades, one novel and one related to the HKU2 clade. All three clades present in Miniopterus bats in China (HKU7, HKU8, and 1A related) were also present in European Miniopterus bats. An additional novel Alphacoronavirus clade (bat CoV [BtCoV]/BNM98-30) was detected in Nyctalus leisleri. A CoV grouping criterion was developed by comparing amino acid identities across an 816-bp fragment of the RNA-dependent RNA polymerases (RdRp) of all accepted mammalian CoV species (RdRp-based grouping units [RGU]). Criteria for defining separate RGU in mammalian CoV were a >4.8% amino acid distance for alphacoronaviruses and a >6.3% distance for betacoronaviruses. All the above-mentioned novel clades represented independent RGU. Strict associations between CoV RGU and host bat genera were confirmed for six independent RGU represented simultaneously in China and Europe. A SARS-related virus (BtCoV/BM48-31/Bulgaria/2008) from a Rhinolophus blasii (Rhi bla) bat was fully sequenced. It is predicted that proteins 3b and 6 were highly divergent from those proteins in all known SARS-related CoV. Open reading frame 8 (ORF8) was surprisingly absent. Surface expression of spike and staining with sera of SARS survivors suggested low antigenic overlap with SARS CoV. However, the receptor binding domain of SARS CoV showed higher similarity with that of BtCoV/BM48-31/Bulgaria/2008 than with that of any Chinese bat-borne CoV. Critical spike domains 472 and 487 were identical and similar, respectively. This study underlines the importance of assessments of the zoonotic potential of widely distributed bat-borne CoV.",,"['Drexler, Jan Felix', 'Gloza-Rausch, Florian', 'Glende, Jörg', 'Corman, Victor Max', 'Muth, Doreen', 'Goettsche, Matthias', 'Seebens, Antje', 'Niedrig, Matthias', 'Pfefferle, Susanne', 'Yordanov, Stoian', 'Zhelyazkov, Lyubomir', 'Hermanns, Uwe', 'Vallo, Peter', 'Lukashev, Alexander', 'Müller, Marcel Alexander', 'Deng, Hongkui', 'Herrler, Georg', 'Drosten, Christian']",,,,
,PMC,Genome-Wide Detection and Characterization of Endogenous Retroviruses in Bos taurus,http://dx.doi.org/10.1128/JVI.00106-10,PMC2950565,,,"Endogenous retroviruses (ERVs) are the proviral phase of exogenous retroviruses that become integrated into a host germ line. They can play an important role in the host genome. Bioinformatic tools have been used to detect ERVs in several vertebrates, primarily primates and rodents. Less information is available regarding ERVs in other mammalian groups, and the source of this information is basically experimental. We analyzed the genome of the cow (Bos taurus) using three different methods. A BLAST-based method detected 928 possible ERVs, LTR_STRUC detected 4,487 elements flanked by long terminal repeats (LTRs), and Retrotector detected 9,698 ERVs. The ERVs were not homogeneously distributed across chromosomes; the number of ERVs was positively correlated with chromosomal size and negatively correlated with chromosomal GC content. The bovine ERVs (BoERVs) were classified into 24 putative families, with 20 of them not previously described. One of these new families, BoERV1, was the most abundant family and appeared to be specific to ruminants. An analysis of representatives of ERV families from rodents, primates, and ruminants showed a phylogenetic relationship following their hosts' relationships. This study demonstrates the importance of using multiple methods when trying to identify new ERVs and shows that the number of bovine ERV families is not as limited as previously thought.",,"['Garcia-Etxebarria, Koldo', 'Jugo, Begoña Marina']",,,,
,PMC,CX(3)CR1(+) CD8α(+) dendritic cells are a steady-state population related to plasmacytoid dendritic cells,http://dx.doi.org/10.1073/pnas.1001562107,PMC2930429,,,"Lymphoid organs are characterized by a complex network of phenotypically distinct dendritic cells (DC) with potentially unique roles in pathogen recognition and immunostimulation. Classical DC (cDC) include two major subsets distinguished in the mouse by the expression of CD8α. Here we describe a subset of CD8α(+) DC in lymphoid organs of naïve mice characterized by expression of the CX(3)CR1 chemokine receptor. CX(3)CR1(+) CD8α(+) DC lack hallmarks of classical CD8α(+) DC, including IL-12 secretion, the capacity to cross-present antigen, and their developmental dependence on the transcriptional factor BatF3. Gene-expression profiling showed that CX(3)CR1(+) CD8α(+) DC resemble CD8α(−) cDC. The microarray analysis further revealed a unique plasmacytoid DC (PDC) gene signature of CX(3)CR1(+) CD8α(+) DC. A PDC relationship of the cells is supported further by the fact that they harbor characteristic D–J Ig gene rearrangements and that development of CX(3)CR1(+) CD8α(+) DC requires E2-2, the critical transcriptional regulator of PDC. Thus, CX(3)CR1(+) CD8α(+) DC represent a unique DC subset, related to but distinct from PDC. Collectively, the expression-profiling data of this study refine the resolution of previous DC definitions, sharpen the border of classical CD8α(+) and CD8α(−) DC, and should assist the identification of human counterparts of murine DC subsets.",,"['Bar-On, Liat', 'Birnberg, Tal', 'Lewis, Kanako L.', 'Edelson, Brian T.', 'Bruder, Dunja', 'Hildner, Kai', 'Buer, Jan', 'Murphy, Kenneth M.', 'Reizis, Boris', 'Jung, Steffen']",,,,
,PMC,Upper alimentary tract papillomas in calves related to papillomavirus infection,,PMC2905008,,,"This study reports 3 cases of spontaneous papillomavirus infection in 1-week-old calves. Thickening of the omasum and abomasum wall, with acute inflammation, necrosis, ulceration, and neoplastic changes were seen in 1 calf. In the other 2, small papillomas were observed in the omasal mucosa, exhibiting proliferation of the parakeratinized epithelium. Papillomavirus antigens were detected by immunohistochemistry and virus-like particles were seen through electron microscopy.",,"['Morris, Winston E.', 'Venzano, Agustín J.', 'Craig, María Isabel', 'Diodati, Julián A.', 'Funes, Daniel', 'Elizondo, Ana', 'Mercado, Elsa', 'Capellino, Felix', 'Delgado, Fernando', 'Blanco-Viera, Javier']",,,,
,PMC,Apolipoproteins in the brain: implications for neurological and psychiatric disorders,http://dx.doi.org/10.2217/CLP.10.37,PMC3058497,,,"The brain is the most lipid-rich organ in the body and, owing to the impermeable nature of the blood–brain barrier, lipid and lipoprotein metabolism within this organ is distinct from the rest of the body. Apolipoproteins play a well-established role in the transport and metabolism of lipids within the CNS; however, evidence is emerging that they also fulfill a number of functions that extend beyond lipid transport and are critical for healthy brain function. The importance of apolipoproteins in brain physiology is highlighted by genetic studies, where apolipoprotein gene polymorphisms have been identified as risk factors for several neurological diseases. Furthermore, the expression of brain apolipoproteins is significantly altered in several brain disorders. The purpose of this article is to provide an up-to-date assessment of the major apolipoproteins found in the brain (ApoE, ApoJ, ApoD and ApoA-I), covering their proposed roles and the factors influencing their level of expression. Particular emphasis is placed on associations with neurological and psychiatric disorders.",,"['Elliott, David A', 'Weickert, Cyndi Shannon', 'Garner, Brett']",,,,
,PMC,Targeting the Vasoprotective Axis of the Renin-Angiotensin System: A Novel Strategic Approach to Pulmonary Hypertensive Therapy,http://dx.doi.org/10.1007/s11906-010-0122-6,PMC2957877,,,"A decade has passed since the discovery of angiotensin-converting enzyme 2 (ACE2), a component of the ACE2–angiotensin (Ang)-(1-7)–Mas counterregulatory axis of the renin angiotensin system (RAS). ACE2 is considered an endogenous regulator of the vasoconstrictive, proliferative, fibrotic, and proinflammatory effects of the ACE–Ang II–angiotensin II type 1 receptor (AT(1)R) axis. Both animal and clinical studies have emerged to define a role for ACE2 in pulmonary arterial hypertension (PAH). There is scientific evidence supporting the concept that ACE2 maintains the RAS balance and plays a protective role in PAH. The activation of pulmonary ACE2 could influence the pathogenesis of PAH and serve as a novel therapeutic target in PAH. Current therapeutic strategies and interventions have limited success, and PAH remains a fatal disease. Thus, more research that establishes the novel therapeutic potential and defines the mechanism of the ACE2–Ang-(1-7)–Mas counterregulatory axis in PAH is needed.",,"['Bradford, Chastity N.', 'Ely, Debra R.', 'Raizada, Mohan K.']",,,,
,PMC,Correlation of Pandemic (H1N1) 2009 Viral Load with Disease Severity and Prolonged Viral Shedding in Children,http://dx.doi.org/10.3201/eid1608.091918,PMC3298297,20678321,NO-CC CODE,Younger children may require a longer isolation period and more aggressive treatment.,2010 Aug,"['Li, Chung-Chen', 'Wang, Lin', 'Eng, Hock-Liew', 'You, Huey-Ling', 'Chang, Ling-Sai', 'Tang, Kuo-Shu', 'Lin, Ying-Jui', 'Kuo, Hsuan-Chang', 'Lee, Ing-Kit', 'Liu, Jien-Wei', 'Huang, Eng-Yen', 'Yang, Kuender D.']",Emerg Infect Dis,,,
,PMC,MyD88 expression in the rat dental follicle: Implications for osteoclastogenesis and tooth eruption,http://dx.doi.org/10.1111/j.1600-0722.2010.00751.x,PMC2914338,,,"Myeloid differentiation factor 88 (MyD88) is a key adaptor molecule in the interleukin-1 (IL-1) and IL-18 Toll-like receptor signaling pathway. Because it is present in dental follicle (DF) cells in vitro, the purpose of this study was to determine its chronological expression in vivo, as well as its possible role in osteoclastogenesis and tooth eruption. An oligo DNA microarray was used to determine gene expression of MyD88 in vivo in the DFs from the first mandibular molars of postnatal rats from days 1–11. The results showed that MyD88 was expressed maximally at day 3. Using siRNA to knock down MyD88 expression in the DF cells also reduced the gene expression of nuclear factor-kappa B-1 (NFKB1) and monocyte chemoattractant protein 1 (MCP-1). IL-1α up-regulated the expression of NFKB1, MCP-1 and receptor activator of nuclear factor kappa B ligand (RANKL), but knockdown of MyD88 nullified this IL-1α effect. Conditioned medium from DF cells with MyD88 knocked down reduced chemotactic activity for mononuclear cells and reduced osteoclastogenesis as opposed to controls. In conclusion, the maximal expression of MyD88 at day 3 in the DF may contribute to the major burst of osteoclastogenesis needed for eruption by up-regulating MCP-1 and RANKL expression.",,"['Liu, Dawen', 'Yao, Shaomian', 'Wise, Gary E.']",,,,
,PMC,In acute pathogenic SIV infection plasmacytoid dendritic cells are depleted from blood and lymph nodes despite mobilization,http://dx.doi.org/10.1111/j.1600-0684.2010.00428.x,PMC2904653,,,"BACKGROUND: Plasmacytoid dendritic cells (pDC) are depleted from blood of individuals with HIV infection associated with progression to disease. It has been postulated but not proven that pDC accumulate in lymph nodes and induce sustained immune activation characteristic of disease. METHODS: The dynamics of the pDC response to acute pathogenic SIV infection of rhesus macaques were studied using methods to track recently divided cells. RESULTS: pDC were lost from blood and lymph nodes in acute SIV infection despite rapid mobilization and recruitment. pDC had a low frequency of infection, were uniformly activated and had increased levels of apoptosis, while maintaining normal function. CONCLUSIONS: pDC mobilization into blood and lymph nodes in acute SIV infection does not keep pace with excessive pDC loss through activation and apoptosis. The depletion of pDC from lymphoid tissues in acutely infected rhesus macaques does not support a pathogenic role for pDC in disease.",,"['Barratt-Boyes, Simon M.', 'Wijewardana, Viskam', 'Brown, Kevin N.']",,,,
,PMC,Swine flu: is panic the key to successful modern health policy?,http://dx.doi.org/10.1258/jrsm.2010.100118,PMC2913064,,,,,"Srinivasan, Rohit",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.01221-10,PMC2897643,,,,,,,,,
,PMC,A Small-Molecule Oxocarbazate Inhibitor of Human Cathepsin L Blocks Severe Acute Respiratory Syndrome and Ebola Pseudotype Virus Infection into Human Embryonic Kidney 293T cells,http://dx.doi.org/10.1124/mol.110.064261,PMC2917856,,,"A tetrahydroquinoline oxocarbazate (PubChem CID 23631927) was tested as an inhibitor of human cathepsin L (EC 3.4.22.15) and as an entry blocker of severe acute respiratory syndrome (SARS) coronavirus and Ebola pseudotype virus. In the cathepsin L inhibition assay, the oxocarbazate caused a time-dependent 17-fold drop in IC(50) from 6.9 nM (no preincubation) to 0.4 nM (4-h preincubation). Slowly reversible inhibition was demonstrated in a dilution assay. A transient kinetic analysis using a single-step competitive inhibition model provided rate constants of k(on) = 153,000 M(−1)s(−1) and k(off) = 4.40 × 10(−5) s(−1) (K(i) = 0.29 nM). The compound also displayed cathepsin L/B selectivity of >700-fold and was nontoxic to human aortic endothelial cells at 100 μM. The oxocarbazate and a related thiocarbazate (PubChem CID 16725315) were tested in a SARS coronavirus (CoV) and Ebola virus-pseudotype infection assay with the oxocarbazate but not the thiocarbazate, demonstrating activity in blocking both SARS-CoV (IC(50) = 273 ± 49 nM) and Ebola virus (IC(50) = 193 ± 39 nM) entry into human embryonic kidney 293T cells. To trace the intracellular action of the inhibitors with intracellular cathepsin L, the activity-based probe biotin-Lys-C5 alkyl linker-Tyr-Leu-epoxide (DCG-04) was used to label the active site of cysteine proteases in 293T lysates. The reduction in active cathepsin L in inhibitor-treated cells correlated well with the observed potency of inhibitors observed in the virus pseudotype infection assay. Overall, the oxocarbazate CID 23631927 was a subnanomolar, slow-binding, reversible inhibitor of human cathepsin L that blocked SARS-CoV and Ebola pseudotype virus entry in human cells.",,"['Shah, Parag P.', 'Wang, Tianhua', 'Kaletsky, Rachel L.', 'Myers, Michael C.', 'Purvis, Jeremy E.', 'Jing, Huiyan', 'Huryn, Donna M.', 'Greenbaum, Doron C.', 'Smith, Amos B.', 'Bates, Paul', 'Diamond, Scott L.']",,,,
,PMC,Mode of Delivery and Infant Respiratory Morbidity Among Infants Born to HIV-1-Infected Women,http://dx.doi.org/10.1097/AOG.0b013e3181e8f38a,PMC2964131,,,"OBJECTIVE: To estimate risk of infant respiratory morbidity associated with cesarean delivery before labor and ruptured membranes among HIV-1-infected women. METHODS: In a prospective cohort study of HIV-1-infected women and their infants, mode of delivery was determined by clinicians at the participating sites. For this analysis, “elective cesarean delivery” was defined as any cesarean delivery, regardless of gestational age, without labor and with duration of ruptured membranes of less than 5 minutes. Nonelective cesarean deliveries were those performed after the onset of labor, rupture of membranes, or both. Vaginal delivery included normal spontaneous and instrument deliveries. Associations between mode of delivery and infant respiratory morbidity were assessed using χ(2) or Fisher’s exact test. Adjusted odds of respiratory distress syndrome by delivery mode were assessed using multivariable logistic regression. RESULTS: Among 1,194 mother–infant pairs, there were significant differences according to mode of delivery in median gestational age (weeks) at delivery (vaginal, n=566, median=38.8; nonelective cesarean, n=216, median=38.0; and elective cesarean, n=412, median 38.1; P<.001) and incidence of respiratory distress syndrome (vaginal, n=9, 1.6%, reference; nonelective cesarean, n=16, 7.4%; elective cesarean, n=18; 4.4%; (P<.001). In analyses adjusted for gestational age and birth weight, mode of delivery was not statistically significantly associated with infant respiratory distress syndrome (P=.10), although a trend toward an increased risk of respiratory distress syndrome among infants delivered by cesarean was suggested (nonelective cesarean adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 0.95–5.67; elective cesarean OR 2.56, 95% CI 1.01– 6.48). CONCLUSION: Respiratory distress syndrome rates associated with elective cesarean delivery among HIV-1-infected women are low, comparable with published rates among uninfected women. There is minimal neonatal respiratory morbidity risk in near-term infants born by elective cesarean delivery to HIV-1-infected women. LEVEL OF EVIDENCE: II",,"['Livingston, Elizabeth G.', 'Huo, Yanling', 'Patel, Kunjal', 'Brogly, Susan B.', 'Tuomala, Ruth', 'Scott, Gwendolyn B.', 'Bardeguez, Arlene', 'Stek, Alice', 'Read, Jennifer S.']",,,,
,PMC,Persistence of Adenovirus Nucleic Acids in Nasopharyngeal Secretions: A Diagnostic Conundrum,http://dx.doi.org/10.1097/INF.0b013e3181d743c8,PMC3206289,,,"BACKGROUND: Polymerase chain reaction (PCR) assays increase the rate of viral detection in clinical specimens, compared with conventional virologic methods. Studies suggest that PCR may detect virus nucleic acid (NA) that persists in the respiratory tract. METHODS: We analyzed virologic data from children having frequent upper respiratory infections (URI) who were followed in a longitudinal study. Nasopharyngeal secretions (NPS) were collected at URI onset and when acute otitis media (AOM) was diagnosed; virus studies were performed using conventional diagnostics and PCR. Repeated presence of adenovirus by PCR was further studied by sequencing and phylogenetic analysis. RESULTS: Of 581 URI episodes in 76 children, 510 viruses were detected. Of the viruses detected by PCR, 15% were those detected previously; repeated positives occurred most frequently with adenovirus. Sequencing results were available in 13 children with repeated adenovirus detection; four patterns of infection were identified (16 instances): 1) adenovirus of the same serotype and strain detected continuously (n=8 instances), 2) adenovirus of different serotypes detected during sequential URI episodes (n=3), 3) adenovirus of the same serotype but different strains detected during sequential URI episodes (n=3) and 4) adenovirus of the same serotype and strain detected intermittently (n=2). CONCLUSIONS: Among children with frequent URIs, repeated positive PCR results for adenovirus NA may represent a new serotype/strain, or persistence of viral NA. Results must be interpreted with caution; clinical correlation and presence of other viruses are important. Further longitudinal studies of children during and after infection are required for better understanding of the clinical significance of positive PCR tests for adenovirus NA in the respiratory tract .",,"['Kalu, Stella U.', 'Loeffelholz, Michael', 'Beck, Eric', 'Patel, Janak A.', 'Revai, Krystal', 'Fan, Jiang', 'Henrickson, Kelly J.', 'Chonmaitree, Tasnee']",,,,
,PMC,Concomitant Respiratory Viral Infections in Children with Kawasaki Disease,http://dx.doi.org/10.1097/INF.0b013e3181dba70b,PMC2927322,,,The role of respiratory viruses in the pathogenesis of Kawasaki disease (KD) remains controversial. In this study we showed that 8.8 % of KD patients had documented respiratory viral infections. Patients with concomitant viral infections had a higher frequency of coronary artery dilatations and were significantly more often diagnosed with incomplete KD. The presence of a concomitant viral infection should not exclude the diagnosis of KD.,,"['Jordan-Villegas, Alejandro', 'Chang, Michael L.', 'Ramilo, Octavio', 'Mejías, Asunción']",,,,
,PMC,Structures of the N- and C-terminal domains of MHV-A59 nucleocapsid protein corroborate a conserved RNA-protein binding mechanism in coronavirus,http://dx.doi.org/10.1007/s13238-010-0079-x,PMC4875274,,,"Coronaviruses are the causative agent of respiratory and enteric diseases in animals and humans. One example is SARS, which caused a worldwide health threat in 2003. In coronaviruses, the structural protein N (nucleocapsid protein) associates with the viral RNA to form the filamentous nucleocapsid and plays a crucial role in genome replication and transcription. The structure of Nterminal domain of MHV N protein also implicated its specific affinity with transcriptional regulatory sequence (TRS) RNA. Here we report the crystal structures of the two proteolytically resistant N- (NTD) and C-terminal (CTD) domains of the N protein from murine hepatitis virus (MHV). The structure of NTD in two different crystal forms was solved to 1.5 Å. The higher resolution provides more detailed structural information than previous reports, showing that the NTD structure from MHV shares a similar overall and topology structure with that of SARS-CoV and IBV, but varies in its potential surface, which indicates a possible difference in RNA-binding module. The structure of CTD was solved to 2.0-Å resolution and revealed a tightly intertwined dimer. This is consistent with analytical ultracentrifugation experiments, suggesting a dimeric assembly of the N protein. The similarity between the structures of these two domains from SARS-CoV, IBV and MHV corroborates a conserved mechanism of nucleocapsid formation for coronaviruses.",,"['Ma, Yanlin', 'Tong, Xiaohang', 'Xu, Xiaoling', 'Li, Xuemei', 'Lou, Zhiyong', 'Rao, Zihe']",,,,
,PMC,"E93R Substitution of Escherichia coli FtsZ Induces Bundling of Protofilaments, Reduces GTPase Activity, and Impairs Bacterial Cytokinesis",http://dx.doi.org/10.1074/jbc.M110.138719,PMC2951251,,,"Recently, we found that divalent calcium has no detectable effect on the assembly of Mycobacterium tuberculosis FtsZ (MtbFtsZ), whereas it strongly promoted the assembly of Escherichia coli FtsZ (EcFtsZ). While looking for potential calcium binding residues in EcFtsZ, we found a mutation (E93R) that strongly promoted the assembly of EcFtsZ. The mutation increased the stability and bundling of the FtsZ protofilaments and produced a dominating effect on the assembly of the wild type FtsZ (WT-FtsZ). Although E93R-FtsZ was found to bind to GTP similarly to the WT-FtsZ, it displayed lower GTPase activity than the WT-FtsZ. E93R-FtsZ complemented for its wild type counterpart as observed by a complementation test using JKD7–1/pKD3 cells. However, the bacterial cells became elongated upon overexpression of the mutant allele. We modeled the structure of E93R-FtsZ using the structures of MtbFtsZ/Methanococcus jannaschi FtsZ (MjFtsZ) dimers as templates. The MtbFtsZ-based structure suggests that the Arg(93)-Glu(138) salt bridge provides the additional stability, whereas the effect of mutation appears to be indirect (allosteric) if the EcFtsZ dimer is similar to that of MjFtsZ. The data presented in this study suggest that an increase in the stability of the FtsZ protofilaments is detrimental for the bacterial cytokinesis.",,"['Jaiswal, Richa', 'Patel, Ronak Y.', 'Asthana, Jayant', 'Jindal, Bhavya', 'Balaji, Petety V.', 'Panda, Dulal']",,,,
,PMC,Highly Sensitive and Quantitative Detection of the H274Y Oseltamivir Resistance Mutation in Seasonal A/H1N1 Influenza Virus,http://dx.doi.org/10.1128/JCM.01031-10,PMC2953111,,,"A C-to-T transition mutation in the neuraminidase gene from seasonal A/H1N1 causes a His-to-Tyr mutation at amino acid position 275 (H274Y, universal N2 numbering), conferring resistance against oseltamivir (Tamiflu). This mutation was first detected in clinical samples in Europe during the 2007-2008 influenza season. Viruses with this mutation reached a prevalence of ∼11% by the end of the season in North American isolates tested by the CDC. We developed a highly sensitive and specific quantitative real-time reverse transcriptase PCR assay to detect the H274Y mutation. This assay utilizes a 5′-methyl-isocytosine (isoC) residue and fluorescent reporters on genotype-specific primers. During PCR, a quencher coupled to isoguanine (isoG) is site-specifically incorporated complementary to the isoC/dye, resulting in loss of fluorescence. Optimization of primers and assay conditions produced a limit of detection of 100 gene copies per reaction for both wild-type and H274Y genotypes. In samples with mixed populations, it can reliably detect as little as a 1% wild-type or 0.1% H274Y component. This high sensitivity makes the assay usable on samples with viral loads too low for dideoxy or pyrosequencing analysis. Additionally, the assay distinguishes seasonal A/H1N1 from A/H3N2, influenza B, or 2009 pandemic A/H1N1, making it useful for influenza virus subtyping as well as for drug resistance detection. We probed seasonal A/H1N1 samples from the 2005-2006, 2006-2007, and 2007-2008 influenza seasons. Data from the new assay closely matched available drug resistance genotype data previously determined by dideoxy sequencing. The H274Y mutation was only found in samples from the 2007-2008 season.",,"['Operario, Darwin J.', 'Moser, Michael J.', 'St. George, Kirsten']",,,,
,PMC,A New Cistron in the Murine Hepatitis Virus Replicase Gene,http://dx.doi.org/10.1128/JVI.00901-10,PMC2937787,,,"We report an RNA-negative, temperature-sensitive (ts) mutant of Murine hepatitis virus, Bristol ts31 (MHV-Brts31), that defines a new complementation group within the MHV replicase gene locus. MHV-Brts31 has near-normal levels of RNA synthesis at the permissive temperature of 33°C but is unable to synthesize viral RNA when the infection is initiated and maintained at the nonpermissive temperature of 39.5°C. Sequence analysis of MHV-Brts31 RNA indicated that a single G-to-A transition at codon 1307 in open reading frame 1a, which results in a replacement of methionine-475 with isoleucine in nonstructural protein 3 (nsp3), was responsible for the ts phenotype. This conclusion was confirmed using a vaccinia virus-based reverse genetics system to produce a recombinant virus, Bristol tsc31 (MHV-Brtsc31), which has the same RNA-negative ts phenotype and complementation profile as those of MHV-Brts31. The analysis of protein synthesis in virus-infected cells showed that, at the nonpermissive temperature, MHV-Brtsc31 was not able to proteolytically process either p150, the precursor polypeptide of the replicase nonstructural proteins nsp4 to nsp10, or the replicase polyprotein pp1ab to produce nsp12. The processing of replicase polyprotein pp1a in the region of nsp1 to nsp3 was not affected. Transmission electron microscopy showed that, compared to revertant virus, the number of double-membrane vesicles in MHV-Brts31-infected cells is reduced at the nonpermissive temperature. These results identify a new cistron in the MHV replicase gene locus and show that nsp3 has an essential role in the assembly of a functional MHV replication-transcription complex.",,"['Stokes, Helen L.', 'Baliji, Surendranath', 'Hui, Chang Guo', 'Sawicki, Stanley G.', 'Baker, Susan C.', 'Siddell, Stuart G.']",,,,
,PMC,Papain-Like Protease 1 from Transmissible Gastroenteritis Virus: Crystal Structure and Enzymatic Activity toward Viral and Cellular Substrates,http://dx.doi.org/10.1128/JVI.00898-10,PMC2937765,,,"Coronaviruses encode two classes of cysteine proteases, which have narrow substrate specificities and either a chymotrypsin- or papain-like fold. These enzymes mediate the processing of the two precursor polyproteins of the viral replicase and are also thought to modulate host cell functions to facilitate infection. The papain-like protease 1 (PL1(pro)) domain is present in nonstructural protein 3 (nsp3) of alphacoronaviruses and subgroup 2a betacoronaviruses. It participates in the proteolytic processing of the N-terminal region of the replicase polyproteins in a manner that varies among different coronaviruses and remains poorly understood. Here we report the first structural and biochemical characterization of a purified coronavirus PL1(pro) domain, that of transmissible gastroenteritis virus (TGEV). Its tertiary structure is compared with that of severe acute respiratory syndrome (SARS) coronavirus PL2(pro), a downstream paralog that is conserved in the nsp3's of all coronaviruses. We identify both conserved and unique structural features likely controlling the interaction of PL1(pro) with cofactors and substrates, including the tentative mapping of substrate pocket residues. The purified recombinant TGEV PL1(pro) was shown to cleave a peptide mimicking the cognate nsp2|nsp3 cleavage site. Like its PL2(pro) paralogs from several coronaviruses, TGEV PL1(pro) was also found to have deubiquitinating activity in an in vitro cleavage assay, implicating it in counteracting ubiquitin-regulated host cell pathways, likely including innate immune responses. In combination with the prior characterization of PL2(pro) from other alphacoronaviruses, e.g., human coronaviruses 229E and NL63, our results unequivocally establish that these viruses employ two PL(pro)s with overlapping specificities toward both viral and cellular substrates.",,"['Wojdyla, Justyna A.', 'Manolaridis, Ioannis', 'van Kasteren, Puck B.', 'Kikkert, Marjolein', 'Snijder, Eric J.', 'Gorbalenya, Alexander E.', 'Tucker, Paul A.']",,,,
,PMC,Viral Infections of the Central Nervous System: Pathogenesis to Therapeutics,http://dx.doi.org/10.1007/s11481-010-9231-x,PMC4995365,,,,,"['Soldan, Samantha S.', 'Jacobson, Steven']",,,,
,PMC,Examining International Clinical Internships for Canadian Physical Therapy Students from 1997 to 2007,http://dx.doi.org/10.3138/physio.62.3.261,PMC2909866,,,"Purpose: To describe international clinical internships (ICIs) for Canadian physical therapy (PT) students, explore the experiences of individuals involved in ICIs, and develop recommendations for future ICIs based on these findings. Methods: This study employed a mixed-methods approach. An online questionnaire surveyed academic coordinators of clinical education (ACCEs, n=14) on the availability, destinations, and number of ICIs from 1997 to 2007. Semi-structured telephone interviews were then conducted with eight PT students, seven ACCEs, and three supervising clinicians to investigate their ICI experiences. Interview transcripts were coded descriptively and thematically using NVivo. Results: ICIs are currently available at 12 of 14 Canadian PT schools. A total of 313 students participated in ICIs in 51 different destination countries from 1997 to 2007. Over this period, increasing numbers of students participated in ICIs and developing countries represented an increasing proportion of ICI destinations. Key themes identified in the interviews were opportunities, challenges, and facilitating factors. Conclusions: ICIs present unique opportunities for Canadian PT students. Recommendations to enhance the quality of future ICIs are (1) clearly defined objectives for ICIs, (2) additional follow-up post-ICI, and (3) improved record keeping and sharing of information on ICI destination countries and host sites.",,"['Crawford, Elizabeth', 'Biggar, John M.', 'Leggett, Adrienne', 'Huang, Adrian', 'Mori, Brenda', 'Nixon, Stephanie A.', 'Landry, Michel D.']",,,,
,PMC,Fundamental differences between the nucleic acid chaperone activities of HIV-1 nucleocapsid protein and Gag or Gag-derived proteins: Biological implications,http://dx.doi.org/10.1016/j.virol.2010.06.042,PMC2963451,,,"The HIV-1 Gag polyprotein precursor has multiple domains including nucleocapsid (NC). Although mature NC and NC embedded in Gag are nucleic acid chaperones (proteins that remodel nucleic acid structure), few studies include detailed analysis of the chaperone activity of partially processed Gag proteins and comparison with NC and Gag. Here we address this issue by using a reconstituted minus-strand transfer system. NC and NC-containing Gag proteins exhibited annealing and duplex destabilizing activities required for strand transfer. Surprisingly, unlike NC, with increasing concentrations, Gag proteins drastically inhibited the DNA elongation step. This result is consistent with “nucleic acid-driven multimerization” of Gag and the reported slow dissociation of Gag from bound nucleic acid, which prevent reverse transcriptase from traversing the template (“roadblock” mechanism). Our findings illustrate one reason why NC (and not Gag) has evolved as a critical cofactor in reverse transcription, a paradigm that might also extend to other retrovirus systems.",,"['Wu, Tiyun', 'Datta, Siddhartha A.K.', 'Mitra, Mithun', 'Gorelick, Robert J.', 'Rein, Alan', 'Levin, Judith G.']",,,,
,PMC,Cytoplasmic Viral Replication Complexes,http://dx.doi.org/10.1016/j.chom.2010.06.010,PMC2921950,,,"Many viruses that replicate in the cytoplasm compartmentalize their genome replication and transcription in organelle-like structures that enhance replication efficiency and protection from host defenses. In particular, recent studies with diverse positive-strand RNA viruses have further elucidated the ultrastructure of membrane-bounded RNA replication complexes and their close coordination with virion assembly and budding. The structure, function and assembly of some positive-strand RNA virus replication complexes have parallels and potential evolutionary links with the replicative cores of double-strand RNA virus and retrovirus virions, and more general similarities with the replication factories of cytoplasmic DNA viruses.",,"['den Boon, Johan A.', 'Diaz, Arturo', 'Ahlquist, Paul']",,,,
,PMC,An Interaction between the Nucleocapsid Protein and a Component of the Replicase-Transcriptase Complex Is Crucial for the Infectivity of Coronavirus Genomic RNA,http://dx.doi.org/10.1128/JVI.01287-10,PMC2937748,,,"The coronavirus nucleocapsid (N) protein plays an essential role in virion assembly via interactions with the large, positive-strand RNA viral genome and the carboxy-terminal endodomain of the membrane protein (M). To learn about the functions of N protein domains in the coronavirus mouse hepatitis virus (MHV), we replaced the MHV N gene with its counterpart from the closely related bovine coronavirus (BCoV). The resulting viral mutant was severely defective, even though individual domains of the N protein responsible for N-RNA, N-M, or N-N interactions were completely interchangeable between BCoV and MHV. The lesion in the BCoV N substitution mutant could be compensated for by reverting mutations in the central, serine- and arginine-rich (SR) domain of the N protein. Surprisingly, a second class of reverting mutations were mapped to the amino terminus of a replicase subunit, nonstructural protein 3 (nsp3). A similarly defective MHV N mutant bearing an insertion of the SR region from the severe acute respiratory syndrome coronavirus N protein was rescued by the same two classes of reverting mutations. Our genetic results were corroborated by the demonstration that the expressed amino-terminal segment of nsp3 bound selectively to N protein from infected cells, and this interaction was RNA independent. Moreover, we found a direct correlation between the N-nsp3 interaction and the ability of N protein to stimulate the infectivity of transfected MHV genomic RNA (gRNA). Our results suggest a role for this previously unknown N-nsp3 interaction in the localization of genomic RNA to the replicase complex at an early stage of infection.",,"['Hurst, Kelley R.', 'Ye, Rong', 'Goebel, Scott J.', 'Jayaraman, Priya', 'Masters, Paul S.']",,,,
,PMC,Hydrocarbon double-stapling remedies the proteolytic instability of a lengthy peptide therapeutic,http://dx.doi.org/10.1073/pnas.1002713107,PMC2922607,,,"The pharmacologic utility of lengthy peptides can be hindered by loss of bioactive structure and rapid proteolysis, which limits bioavailability. For example, enfuvirtide (Fuzeon, T20, DP178), a 36-amino acid peptide that inhibits human immunodeficiency virus type 1 (HIV-1) infection by effectively targeting the viral fusion apparatus, has been relegated to a salvage treatment option mostly due to poor in vivo stability and lack of oral bioavailability. To overcome the proteolytic shortcomings of long peptides as therapeutics, we examined the biophysical, biological, and pharmacologic impact of inserting all-hydrocarbon staples into an HIV-1 fusion inhibitor. We find that peptide double-stapling confers striking protease resistance that translates into markedly improved pharmacokinetic properties, including oral absorption. We determined that the hydrocarbon staples create a proteolytic shield by combining reinforcement of overall α-helical structure, which slows the kinetics of proteolysis, with complete blockade of peptide cleavage at constrained sites in the immediate vicinity of the staple. Importantly, double-stapling also optimizes the antiviral activity of HIV-1 fusion peptides and the antiproteolytic feature extends to other therapeutic peptide templates, such as the diabetes drug exenatide (Byetta). Thus, hydrocarbon double-stapling may unlock the therapeutic potential of natural bioactive polypeptides by transforming them into structurally fortified agents with enhanced bioavailability.",,"['Bird, Gregory H.', 'Madani, Navid', 'Perry, Alisa F.', 'Princiotto, Amy M.', 'Supko, Jeffrey G.', 'He, Xiaoying', 'Gavathiotis, Evripidis', 'Sodroski, Joseph G.', 'Walensky, Loren D.']",,,,
,PMC,Synthetic biology for translational research,,PMC2923862,,,"Synthetic biology involves the engineering of proteins, signaling pathways and even whole organisms using modular designs and formats. A major tool of synthetic biology is artificial gene synthesis, which provides a direct means from a conceptualized DNA sequence to the corresponding physical DNA for the construction of a variety of biological components. To date, synthetic biology has often been used to answer fundamental questions in basic research, but now is poised to greatly enhance translational research. In this review, we discuss several translational applications of synthetic biology including the construction of novel diagnostics and vaccines, development of new synthetic pathways for drug screening and biosynthesis, and the creation of engineered viruses and microbes to fight human disease. Together these and other novel translational applications of artificial gene synthesis and synthetic biology have the opportunity to make major advances for improving human health.",,"['Burbelo, Peter D', 'Ching, Kathryn H', 'Han, Brian L', 'Klimavicz, Caitlin M', 'Iadarola, Michael J']",,,,
,PMC,Sequential nearest-neighbor effects on computed (13)C(α) chemical shifts,http://dx.doi.org/10.1007/s10858-010-9435-7,PMC2970923,,,"To evaluate sequential nearest-neighbor effects on quantum-chemical calculations of (13)C(α) chemical shifts, we selected the structure of the nucleic acid binding (NAB) protein from the SARS coronavirus determined by NMR in solution (PDB id 2K87). NAB is a 116-residue α/β protein, which contains 9 prolines and has 50% of its residues located in loops and turns. Overall, the results presented here show that sizeable nearest-neighbor effects are seen only for residues preceding proline, where Pro introduces an overestimation, on average, of 1.73 ppm in the computed (13)C(α) chemical shifts. A new ensemble of 20 conformers representing the NMR structure of the NAB, which was calculated with an input containing backbone torsion angle constraints derived from the theoretical (13)C(α) chemical shifts as supplementary data to the NOE distance constraints, exhibits very similar topology and comparable agreement with the NOE constraints as the published NMR structure. However, the two structures differ in the patterns of differences between observed and computed (13)C(α) chemical shifts, Δ(ca,i), for the individual residues along the sequence. This indicates that the Δ(ca,i) -values for the NAB protein are primarily a consequence of the limited sampling by the bundles of 20 conformers used, as in common practice, to represent the two NMR structures, rather than of local flaws in the structures.",,"['Vila, Jorge A.', 'Serrano, Pedro', 'Wüthrich, Kurt', 'Scheraga, Harold A.']",,,,
,PMC,应用多肽芯片研究非小细胞肺癌患者血清中的EGFR自身抗体,http://dx.doi.org/10.3779/j.issn.1009-3419.2010.07.13,PMC6000384,,,"BACKGROUND AND OBJECTIVE: Autoantibodies as new tumor markers may play an important role in the early diagnosis and evaluating the prognosis of lung cancer. In this study, we detect epidermal growth factor receptor (EGFR) autoantibodies using peptide array and screen the epitopes which are recognized by EGFR autoantibodies. METHODS: Peptide array covering the extracellular domain of EGFR protein was synthesized by a synthesizer (ASPSL) made by Intavis company. EGFR autoantibodies in the serums of non-small cell lung cancer patients was detected using peptide array. RESULTS: Six of 20 patients were found to have EGFR autoantibodis. The positive rate is 30%. Nine high frequency spots were found in the 6 positive patients and 8 high frequency spots clustered in the Ⅲ and Ⅳ domains. CONCLUSION: These findings will offer new clues for the futher studies of EGFR and EGFR autoantibodies.",,"[None, None, None, None, None, None]",,,,
,PMC,Identification of a Dendrimeric Heparan Sulfate-Binding Peptide That Inhibits Infectivity of Genital Types of Human Papillomaviruses,http://dx.doi.org/10.1128/AAC.00471-10,PMC2944621,,,"Peptide dendrimers consist of a peptidyl branching core and/or covalently attached surface functional units. They show a variety of biological properties, including antiviral activity. In this study, a minilibrary of linear, dimeric, and dendrimeric peptides containing clusters of basic amino acids was evaluated for in vitro activity against human papillomaviruses (HPVs). The peptide dendrimer SB105-A10 was found to be a potent inhibitor of genital HPV types (i.e., types 16, 18, and 6) in pseudovirus-based neutralization assays. The 50% inhibitory concentration was between 2.8 and 4.2 μg/ml (0.59 and 0.88 μM), and no evidence of cytotoxicity was observed. SB105-A10 interacts with immobilized heparin and with heparan sulfates exposed on the cell surface, most likely preventing virus attachment. The findings from this study indicate SB105-A10 to be a leading candidate compound for further development as an active ingredient of a topical microbicide against HPV and other sexually transmitted viral infections.",,"['Donalisio, Manuela', 'Rusnati, Marco', 'Civra, Andrea', 'Bugatti, Antonella', 'Allemand, Donatella', 'Pirri, Giovanna', 'Giuliani, Andrea', 'Landolfo, Santo', 'Lembo, David']",,,,
,PMC,Ras-related protein Rab10 facilitates TLR4 signaling by promoting replenishment of TLR4 onto the plasma membrane,http://dx.doi.org/10.1073/pnas.1009428107,PMC2922283,,,"The Toll-like receptor (TLR)4 receptor complex, TLR4/MD-2, plays an important role in the inflammatory response against lipopolysaccharide, a ubiquitous membrane component in Gram-negative bacteria. Ligand recognition by TLR4 initiates multiple intracellular signaling pathways, leading to production of proinflammatory mediators and type I IFN. Ligand interaction also leads to internalization of the surface receptor complex into lysosomes, leading to the degradation of TLR4 and the termination of LPS response. However, surface level of TLR4 receptor complex is maintained via continuous replenishment of TLR4 from intracellular compartments like Golgi and endosomes. Here we show that continuous replenishment of TLR4 from Golgi to plasma membrane is regulated by the small GTPase Rab10, which is essential for optimal macrophage activation following LPS stimulation. Expression of Rab10 is inducible by LPS. Blockade of Rab10 function leads to decreased membrane TLR4 expression and diminished production of inflammatory cytokines and interferons upon LPS stimulation. These findings suggest that Rab10 expression provides a mechanism to refine TLR4 signaling by regulating the trafficking rate of TLR4 onto the plasma membrane. In addition, we show that altered Rab10 expression in macrophages influences disease severity in an in vivo model of LPS-induced acute lung injury, suggesting Rab10 as a possible therapeutic target for human acute respiratory distress syndrome (ARDS).",,"['Wang, Di', 'Lou, Jun', 'Ouyang, Chuan', 'Chen, Weilin', 'Liu, Yiqi', 'Liu, Xinyuan', 'Cao, Xuetao', 'Wang, Jianli', 'Lu, Linrong']",,,,
,PMC,Coexistence of two adamantane binding sites in the influenza A M2 ion channel,http://dx.doi.org/10.1073/pnas.1002051107,PMC2922235,,,"The influenza A virus contains a proton-selective ion channel (M2) that is the target of the adamantane family of drug inhibitors. Two recently published studies relating to adamantane binding of the M2 ion channel using X-ray crystallography and solution NMR have reignited interest in the potential use of adamantanes in combating the spread of influenza A. However, these two studies propose different binding sites for the adamantane drugs with the X-ray M2/amantadine structure favoring an ion channel pore-binding model and the solution NMR M2/rimantadine structure suggesting the existence of a lipid-facing binding pocket. We conducted a series of surface plasmon resonance (SPR) experiments designed to accurately measure the affinity of amantadine and rimantadine to M2 ion channels embedded in 1,2-dimyristoyl-sn-glycero-phosphocholine (DMPC) liposomes. We find that this class of drug is capable of binding M2 with two different affinities in the order of 10(−4) and 10(−7) M, suggesting that both proposed binding sites are feasible. Furthermore, by examining drug binding to M2 mutant constructs (V27A, S31N, and D44A), it was possible to probe the location of the two binding sites. We show that a high-affinity binding site corresponds to the M2 ion channel pore whereas the secondary, low-affinity binding site can be attributed to the lipid face of the pore. These SPR results are in excellent agreement with the most recent solid-state NMR study of amantadine-bound M2 in lipid bilayers and provide independent support that the ion channel pore-binding site is responsible for the pharmacological activity elicited by the adamantane drugs.",,"['Rosenberg, Matthew R.', 'Casarotto, Marco G.']",,,,
,PMC,Molecular epidemiology of infectious diseases - expanding horizons for IJMEG,,PMC3076772,,,,,"['Xiao, Lihua', 'Kehoe, Patrick G']",,,,
,PMC,Contribution of CD8 T lymphocytes to the immuno-pathogenesis of multiple sclerosis and its animal models,http://dx.doi.org/10.1016/j.bbadis.2010.07.006,PMC5052066,,,"Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by multi-focal demyelination, axonal loss, and immune cell infiltration. Numerous immune mediators are detected within MS lesions, including CD4(+) and CD8(+) T lymphocytes suggesting that they participate in the related pathogenesis. Although CD4(+) T lymphocytes are traditionally considered the main actors in MS immunopathology, multiple lines of evidence suggest that CD8(+) T lymphocytes are also implicated in the pathogenesis. In this review, we outline the recent literature pertaining to the potential roles of CD8(+) T lymphocytes both in MS and its animal models. The CD8(+) T lymphocytes detected in MS lesions demonstrate characteristics of activated and clonally expanded cells supporting the notion that these cells actively contribute to the observed injury. Moreover, several experimental in vivo models mediated by CD8(+) T lymphocytes recapitulate important features of the human disease. Whether the CD8(+) T cells can induce or aggravate tissue destruction in the CNS needs to be fully explored. Strengthening our understanding of the pathogenic potential of CD8(+) T cells in MS should provide promising new avenues for the treatment of this disabling inflammatory disease.",,"['Mars, Lennart T.', 'Saikali, Philippe', 'Liblau, Roland S.', 'Arbour, Nathalie']",,,,
,PMC,Lycorine sensitizes CD40 ligand-protected chronic lymphocytic leukemia cells to bezafibrate- and medroxyprogesterone acetate-induced apoptosis but dasatanib does not overcome reported CD40-mediated drug resistance,http://dx.doi.org/10.3324/haematol.2010.027821,PMC2966911,,,"BACKGROUND: Tumor cells in chronic lymphocytic leukemia accumulate in the periphery through the proliferation of a minority of cells in lymph nodes. The proliferative and survival signals in these proliferation centers include interactions with T lymphocytes expressing CD40 ligand. We have demonstrated that the low toxicity combination of bezafibrate and medroxyprogesterone acetate induces mitochondrial superoxide-mediated apoptosis of non-CD40-liganded cells but not of cells exposed to CD40 ligand. Here, we assessed the ability of dasatinib and lycorine to restore bezafibrate- and medroxyprogesterone acetate- induced apoptosis in cells exposed to CD40 ligand. In parallel experiments we compared the ability of dasatinib to induce apoptosis of cells co-treated with fludarabine. DESIGN AND METHODS: Primary chronic lymphocytic leukemia and peripheral blood mononuclear cells were exposed to drug combinations for 72 hours on control and CD40 ligand-expressing fibroblast monolayers. Cells were harvested and analyzed for apoptosis and levels of mitochondrial superoxide using flow cytometry. In some experiments cells were removed from CD40 ligand at 48 hours, retreated and analyzed after a further 24 hours. The effect of CD40 ligand and drug treatments on mitochondrial superoxide levels were assessed. RESULTS: As previously described, dasatinib rendered cells sensitive to fludarabine but only when CD40 ligand was removed for the last 24 hours of culture. In contrast, lycorine restored the bezafibrate- and medroxyprogesterone acetate-induced apoptosis associated with mitochondrial superoxide even during continuous exposure to CD40 ligand. Furthermore, combined bezafibrate, medroxyprogesterone acetate and lycorine had little effect against normal peripheral blood mononuclear cells, whereas dasatinib with fludarabine induced high levels of apoptosis. CONCLUSIONS: Our data indicate the potential of bezafibrate, medroxyprogesterone acetate and lycorine as novel therapy in chronic lymphocytic leukemia and have important implications for the reported potential of c-abl kinase inhibitors in this disease.",,"['Hayden, Rachel E.', 'Pratt, Guy', 'Drayson, Mark T.', 'Bunce, Chris M.']",,,,
,PMC,Protein Kinase R Is Responsible for the Phosphorylation of eIF2α in Rotavirus Infection,http://dx.doi.org/10.1128/JVI.00625-10,PMC2950594,,,"The eukaryotic initiation translation factor 2 (eIF2) represents a key point in the regulation of protein synthesis. This factor delivers the initiator Met-tRNA to the ribosome, a process that is conserved in all eukaryotic cells. Many types of stress reduce global translation by triggering the phosphorylation of the α subunit of eIF2, which reduces the formation of the preinitiation translation complexes. Early during rotavirus infection, eIF2α becomes phosphorylated, and even under these conditions viral protein synthesis is not affected, while most of the cell protein synthesis is blocked. Here, we found that the kinase responsible for the phosphorylation of eIF2α in rotavirus-infected cells is PKR, since in mouse embryonic fibroblasts deficient in the kinase domain of PKR, or in MA104 cells where the expression of PKR was knocked down by RNA interference, eIF2α was not phosphorylated upon rotavirus infection. The viral component responsible for the activation of PKR seems to be viral double-stranded RNA, which is found in the cytoplasm of infected cells, outside viroplasms. Taken together, these results suggest that rotaviruses induce the PKR branch of the interferon system and have evolved a mechanism to translate its proteins, surpassing the block imposed by eIF2α phosphorylation.",,"['Rojas, Margarito', 'Arias, Carlos F.', 'López, Susana']",,,,
,PMC,The 7a Accessory Protein of Severe Acute Respiratory Syndrome Coronavirus Acts as an RNA Silencing Suppressor,http://dx.doi.org/10.1128/JVI.00748-10,PMC2937820,,,"RNA silencing suppressors (RSSs) are well studied for plant viruses but are not well defined to date for animal viruses. Here, we have identified an RSS from a medically important positive-sense mammalian virus, Severe acute respiratory syndrome coronavirus. The viral 7a accessory protein suppressed both transgene and virus-induced gene silencing by reducing the levels of small interfering RNA (siRNA). The suppression of silencing was analyzed by two independent assays, and the middle region (amino acids [aa] 32 to 89) of 7a was responsible for suppression. Finally, the RNA suppression property and the enhancement of heterologous replicon activity by the 7a protein were confirmed for animal cell lines.",,"['Karjee, Sumona', 'Minhas, Ankita', 'Sood, Vikas', 'Ponia, Sanket S.', 'Banerjea, Akhil C.', 'Chow, Vincent T. K.', 'Mukherjee, Sunil K.', 'Lal, Sunil K.']",,,,
,PMC,Genetic Determinants of Mouse Hepatitis Virus Strain 1 Pneumovirulence,http://dx.doi.org/10.1128/JVI.00330-10,PMC2937641,,,"We report here investigation into the genetic basis of mouse hepatitis virus strain 1 (MHV-1) pneumovirulence. Sequencing of the 3′ one-third of the MHV-1 genome demonstrated that the genetic organization of MHV-1 was similar to that of other strains of MHV. The hemagglutinin esterase (HE) protein was truncated, and reverse transcription-PCR (RT-PCR) studies confirmed previous work that suggested that the MHV-1 HE is a pseudogene. Targeted recombination was used to select chimeric viruses containing either the MHV-1 S gene or genes encoding all of the MHV-1 structural proteins, on an MHV-A59 background. Challenge studies in mice demonstrated that expression of the MHV-1 S gene within the MHV-A59 background (rA59/S(MHV-1)) increased the pneumovirulence of MHV-A59, and mice infected with this recombinant virus developed pulmonary lesions that were similar to those observed with MHV-1, although rA59/S(MHV-1) was significantly less virulent. Chimeras containing all of the MHV-1 structural genes on an MHV-A59 background were able to reproduce the severe acute respiratory syndrome (SARS)-like pathology observed with MHV-1 and reproducibly increased pneumovirulence relative to rA59/S(MHV-1), but were still much less virulent than MHV-1. These data suggest that important determinants of pneumopathogenicity are contained within the 3′ one-third of the MHV-1 genome, but additional important virulence factors must be encoded in the genome upstream of the S gene. The severity of the pulmonary lesions observed correlates better with elevated levels of inflammatory cytokines than with viral replication in the lungs, suggesting that pulmonary disease has an important immunological component.",,"['Leibowitz, Julian L.', 'Srinivasa, Rajiv', 'Williamson, Shawn T.', 'Chua, Ming Ming', 'Liu, Mingfeng', 'Wu, Samantha', 'Kang, Hyojeung', 'Ma, Xue-Zhong', 'Zhang, Jianhua', 'Shalev, Itay', 'Smith, Robert', 'Phillips, Melville J.', 'Levy, Gary A.', 'Weiss, Susan R.']",,,,
,PMC,Inhibition of the Ubiquitin-Proteasome System Affects Influenza A Virus Infection at a Postfusion Step,http://dx.doi.org/10.1128/JVI.01048-10,PMC2937638,,,"We have demonstrated that influenza A virus (IAV) RNA synthesis depends on the ubiquitin-proteasome system. IAV replication was reduced both by proteasome inhibitors and in E36ts20 cells, which contain the thermolabile ubiquitin-activating enzyme E1. While virus entry was not affected in E36ts20 cells, the proteasome inhibitor MG132 retained viral particles in the cytoplasm. Addition-removal experiments of MG132 in combination with bafilomycin A1, a well-established inhibitor of IAV entry and fusion, showed that MG132 affected IAV infection at a postfusion step. This was confirmed by the lack of inhibition of IAV entry by proteasome inhibitors in a virus-like particle fusion assay.",,"['Widjaja, Ivy', 'de Vries, Erik', 'Tscherne, Donna M.', 'García-Sastre, Adolfo', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.']",,,,
,PMC,"Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Novel Protease Inhibitors: Design, Synthesis, Protein-Ligand X-ray Structure and Biological Evaluation",http://dx.doi.org/10.1021/jm1004489,PMC2918394,,,"The design, synthesis, X-ray crystal structure, molecular modeling, and biological evaluation of a series of new generation SARS-CoV PLpro inhibitors are described. A new lead compound 3 (6577871) was identified via high-throughput screening of a diverse chemical library. Subsequently, we carried out lead optimization and structure-activity studies to provide a series of improved inhibitors that show potent PLpro inhibition and antiviral activity against SARS-CoV infected Vero E6 cells. Interestingly, the (S)-Me inhibitor 15h (enzyme IC(50) = 0.56 μM; antiviral EC(50) = 9.1 μM) and the corresponding (R)-Me 15g (IC(50) = 0.32 μM; antiviral EC(50) = 9.1 μM) are the most potent compounds in this series, with nearly equivalent enzymatic inhibition and antiviral activity. A protein-ligand X-ray structure of 15g-bound SARS-CoV PLpro and a corresponding model of 15h docked to PLpro provide intriguing molecular insight into the ligand-binding site interactions.",,"['Ghosh, Arun K.', 'Takayama, Jun', 'Rao, Kalapala Venkateswara', 'Ratia, Kiira', 'Chaudhuri, Rima', 'Mulhearn, Debbie C.', 'Lee, Hyun', 'Nichols, Daniel B.', 'Baliji, Surendranath', 'Baker, Susan C.', 'Johnson, Michael E.', 'Mesecar, Andrew D.']",,,,
,PMC,Long-Lasting Protective Antiviral Immunity Induced by Passive Immunotherapies Requires both Neutralizing and Effector Functions of the Administered Monoclonal Antibody,http://dx.doi.org/10.1128/JVI.00568-10,PMC2937798,,,"Using FrCas(E) retrovirus-infected newborn mice as a model system, we have shown recently that a long-lasting antiviral immune response essential for healthy survival emerges after a short treatment with a neutralizing (667) IgG2a isotype monoclonal antibody (MAb). This suggested that the mobilization of adaptive immunity by administered MAbs is key for the success in the long term for the MAb-based passive immunotherapy of chronic viral infections. We have addressed here whether the anti-FrCas(E) protective endogenous immunity is the mere consequence of viral propagation blunting, which would simply give time to the immune system to react, and/or to actual immunomodulation by the MAb during the treatment. To this aim, we have compared viral replication, disease progression, and antiviral immune responses between different groups of infected mice: (i) mice treated with either the 667 MAb, its F(ab′)(2) fragment, or an IgM (672) with epitopic specificity similar to that of 667 but displaying different effector functions, and (ii) mice receiving no treatment but infected with a low viral inoculum reproducing the initial viral expansion observed in their infected/667 MAb-treated counterparts. Our data show that the reduction of FrCas(E) propagation is insufficient on its own to induce protective immunity and support a direct immunomodulatory action of the 667 MAb. Interestingly, they also point to sequential actions of the administered MAb. In a first step, viral propagation is exclusively controlled by 667 neutralizing activity, and in a second one, this action is complemented by FcγR-binding-dependent mechanisms, which most likely combine infected cell cytolysis and the modulation of the antiviral endogenous immune response. Such complementary effects of administered MAbs must be taken into consideration for the improvement of future antiviral MAb-based immunotherapies.",,"['Nasser, Roudaina', 'Pelegrin, Mireia', 'Michaud, Henri-Alexandre', 'Plays, Marc', 'Piechaczyk, Marc', 'Gros, Laurent']",,,,
,PMC,T Cell Responses Are Required for Protection from Clinical Disease and for Virus Clearance in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice,http://dx.doi.org/10.1128/JVI.01049-10,PMC2937604,,,"A dysregulated innate immune response and exuberant cytokine/chemokine expression are believed to be critical factors in the pathogenesis of severe acute respiratory syndrome (SARS), caused by a coronavirus (SARS-CoV). However, we recently showed that inefficient immune activation and a poor virus-specific T cell response underlie severe disease in SARS-CoV-infected mice. Here, we extend these results to show that virus-specific T cells, in the absence of activation of the innate immune response, were sufficient to significantly enhance survival and diminish clinical disease. We demonstrated that T cells are responsible for virus clearance, as intravenous adoptive transfer of SARS-CoV-immune splenocytes or in vitro-generated T cells to SCID or BALB/c mice enhanced survival and reduced virus titers in the lung. Enhancement of the number of virus-specific CD8 T cells by immunization with SARS-CoV peptide-pulsed dendritic cells also resulted in a robust T cell response, earlier virus clearance, and increased survival. These studies are the first to show that T cells play a crucial role in SARS-CoV clearance and that a suboptimal T cell response contributes to the pathological changes observed in SARS. They also provide a new approach to SARS vaccine design.",,"['Zhao, Jincun', 'Zhao, Jingxian', 'Perlman, Stanley']",,,,
,PMC,The landscape genetics of infectious disease emergence and spread,http://dx.doi.org/10.1111/j.1365-294X.2010.04679.x,PMC3060346,,,"The spread of parasites is inherently a spatial process often embedded in physically complex landscapes. It is therefore not surprising that infectious disease researchers are increasingly taking a landscape genetics perspective to elucidate mechanisms underlying basic ecological processes driving infectious disease dynamics and to understand the linkage between spatially-dependent population processes and the geographic distribution of genetic variation within both hosts and parasites. The increasing availability of genetic information on hosts and parasites when coupled to their ecological interactions can lead to insights for predicting patterns of disease emergence, spread, and control. Here, we review research progress in this area based on four different motivations for the application of landscape genetics approaches: (1) assessing the spatial organization of genetic variation in parasites as a function of environmental variability, (2) using host population genetic structure as a means to parameterize ecological dynamics that indirectly influence parasite populations, e.g. gene flow and movement pathways across heterogeneous landscapes and the concurrent transport of infectious agents, (3) elucidating the temporal and spatial scales of disease processes, and (4) reconstructing and understanding infectious disease invasion. Throughout this review, we emphasise that landscape genetic principles are relevant to infection dynamics across a range of scales from within host dynamics to global geographic patterns and that they can also be applied to unconventional “landscapes” such as heterogeneous contact networks underlying the spread of human and livestock diseases. We conclude by discussing some general considerations and problems for inferring epidemiological processes from genetic data and try to identify possible future directions and applications for this rapidly expanding field.",,"['Biek, Roman', 'Real, Leslie A.']",,,,
,PMC,Emotions as infectious diseases in a large social network: the SISa model,http://dx.doi.org/10.1098/rspb.2010.1217,PMC2992714,,,"Human populations are arranged in social networks that determine interactions and influence the spread of diseases, behaviours and ideas. We evaluate the spread of long-term emotional states across a social network. We introduce a novel form of the classical susceptible–infected–susceptible disease model which includes the possibility for ‘spontaneous’ (or ‘automatic’) infection, in addition to disease transmission (the SISa model). Using this framework and data from the Framingham Heart Study, we provide formal evidence that positive and negative emotional states behave like infectious diseases spreading across social networks over long periods of time. The probability of becoming content is increased by 0.02 per year for each content contact, and the probability of becoming discontent is increased by 0.04 per year per discontent contact. Our mathematical formalism allows us to derive various quantities from the data, such as the average lifetime of a contentment ‘infection’ (10 years) or discontentment ‘infection’ (5 years). Our results give insight into the transmissive nature of positive and negative emotional states. Determining to what extent particular emotions or behaviours are infectious is a promising direction for further research with important implications for social science, epidemiology and health policy. Our model provides a theoretical framework for studying the interpersonal spread of any state that may also arise spontaneously, such as emotions, behaviours, health states, ideas or diseases with reservoirs.",,"['Hill, Alison L.', 'Rand, David G.', 'Nowak, Martin A.', 'Christakis, Nicholas A.']",,,,
,PMC,Stem Cells and Cell Therapy Approaches in Lung Biology and Diseases,http://dx.doi.org/10.1016/j.trsl.2010.06.007,PMC4201367,,,"Cell-based therapies with embryonic or adult stem cells, including induced pluripotent stem cells, have emerged as potential novel approaches for several devastating and otherwise incurable lung diseases including emphysema, pulmonary fibrosis, pulmonary hypertension, and the acute respiratory distress syndrome. Although initial studies suggested engraftment of exogenously administered stem cells in lung, this is now generally felt to be a rare occurrence of uncertain physiologic significance. However, more recent studies have demonstrated paracrine effects of administered cells, including stimulation of angiogenesis and modulation of local inflammatory and immune responses in mouse lung disease models. Based on these studies and on safety and initial efficacy data from trials of adult stem cells in other diseases, groundbreaking clinical trials of cell-based therapy have been initiated for pulmonary hypertension and for chronic obstructive pulmonary disease. In parallel, the identity and role of endogenous lung progenitor cells in development and in repair from injury and potential contribution as lung cancer stem cells continue to be elucidated. Most recently, novel bioengineering approaches have been applied to develop functional lung tissue ex vivo. Advances in each of these areas will be described in this review with particular reference to animal models.",,"['Sueblinvong, Viranuj', 'Weiss, Daniel J.']",,,,
,PMC,Sequence-Function Analysis of the Sendai virus L protein domain VI,http://dx.doi.org/10.1016/j.virol.2010.06.019,PMC2923248,,,"The large (about 2200 amino acids) L polymerase protein of nonsegmented negative-strand RNA viruses (order Mononegavirales) has six conserved sequence regions (“domains”) postulated to constitute the specific enzymatic activities involved in viral mRNA synthesis, 5′-end capping, cap methylation, 3′ polyadenylation, and genomic RNA replication. Previous studies with vesicular stomatitis virus identified amino acid residues within the L protein domain VI required for mRNA cap methylation. In our recent study we analyzed four amino acid residues within domain VI of the Sendai virus L protein and our data indicated that there could be differences in L protein sequence requirements for cap methylation in two different families of Mononegavirales - rhabdoviruses and paramyxoviruses. In this study, we conducted a more comprehensive mutational analysis by targeting the entire SeV L protein domain VI, creating twenty-four L mutants, and testing these mutations for their effects on viral mRNA synthesis, cap methylation, viral genome replication and virus growth kinetics. Our analysis identified several residues required for successful cap methylation and virus replication and clearly showed the importance of the K-D-K-E tetrad and glycine-rich motif in the SeV cap methylation. This study is the first extensive sequence analysis of the L protein domain VI in the family Paramyxoviridae, and it confirms structural and functional similarity of this domain across different families of the order Mononegavirales.",,"['Murphy, Andrea M.', 'Moerdyk-Schauwecker, Megan', 'Mushegian, Arcady', 'Grdzelishvili, Valery Z.']",,,,
,PMC,Palladium-Catalyzed Aryl Amination Reactions of 6-Bromo- and 6-Chloropurine Nucleosides,http://dx.doi.org/10.1002/adsc.200900728,PMC3148652,,,"Palladium-catalyzed C–N bond forming reactions of 6-bromo- as well as 6-chloropurine ribonucleosides and the 2’-deoxy analogues with aryl amines are described. Efficient conversions were observed with Pd(OAc)(2)/Xantphos/Cs(2)CO(3), in PhMe at 100 °C. Reactions of the bromo nucleoside derivatives could be conducted at a lowered catalytic loading (5 mol % Pd(OAc)(2)/7.5 mol % Xantphos), whereas good product yields were obtained with a higher catalyst load (10 mol % Pd(OAc)(2)/15 mol % Xantphos) when the chloro analogue was employed. Among the examples evaluated, silyl protection for the hydroxyls appears better as compared to acetyl. The methodology has been evaluated via reactions with a variety of aryl amines and by synthesis of biologically relevant deoxyadenosine and adenosine dimers. This is the first detailed analysis of aryl amination reactions of 6-chloropurine nucleosides, and comparison of the two halogenated nucleoside substrates.",,"['Thomson, Paul F.', 'Lagisetty, Pallavi', 'Balzarini, Jan', 'De Clercq, Erik', 'Lakshman, Mahesh K.']",,,,
,PMC,Evaluation of reference genes for quantitative reverse‐transcription polymerase chain reaction normalization in infected tomato plants,http://dx.doi.org/10.1111/j.1364-3703.2010.00646.x,PMC6640390,,,"The quantification of messenger RNA expression levels by real‐time reverse‐transcription polymerase chain reaction requires the availability of reference genes that are stably expressed regardless of the experimental conditions under study. We examined the expression variations of a set of eight candidate reference genes in tomato leaf and root tissues subjected to the infection of five taxonomically and molecularly different plant viruses and a viroid, inducing diverse pathogenic effects on inoculated plants. Parallel analyses by three commonly used dedicated algorithms, geNorm, NormFinder and BestKeeper, showed that different viral infections and tissues of origin influenced, to some extent, the expression levels of these genes. However, all algorithms showed high levels of stability for glyceraldehyde 3‐phosphate dehydrogenase and ubiquitin, indicated as the most suitable endogenous transcripts for normalization in both tissue types. Actin and uridylate kinase were also stably expressed throughout the infected tissues, whereas cyclophilin showed tissue‐specific expression stability only in root samples. By contrast, two widely employed reference genes, 18S ribosomal RNA and elongation factor 1α, demonstrated highly variable expression levels that should discourage their use for normalization. In addition, expression level analysis of ascorbate peroxidase and superoxide dismutase showed the modulation of the two genes in virus‐infected tomato leaves and roots. The relative quantification of the two genes varied according to the reference genes selected, thus highlighting the importance of the choice of the correct normalization method in such experiments.",,"['MASCIA, TIZIANA', 'SANTOVITO, ELISA', 'GALLITELLI, DONATO', 'CILLO, FABRIZIO']",,,,
,PMC,2009 Pandemic Influenza A (H1N1) : Pathology and Pathogenesis of 100 Fatal Cases in the United States,http://dx.doi.org/10.2353/ajpath.2010.100115,PMC2893660,,,"In the spring of 2009, a novel influenza A (H1N1) virus emerged in North America and spread worldwide to cause the first influenza pandemic since 1968. During the first 4 months, over 500 deaths in the United States had been associated with confirmed 2009 pandemic influenza A (H1N1) [2009 H1N1] virus infection. Pathological evaluation of respiratory specimens from initial influenza-associated deaths suggested marked differences in viral tropism and tissue damage compared with seasonal influenza and prompted further investigation. Available autopsy tissue samples were obtained from 100 US deaths with laboratory-confirmed 2009 H1N1 virus infection. Demographic and clinical data of these case-patients were collected, and the tissues were evaluated by multiple laboratory methods, including histopathological evaluation, special stains, molecular and immunohistochemical assays, viral culture, and electron microscopy. The most prominent histopathological feature observed was diffuse alveolar damage in the lung in all case-patients examined. Alveolar lining cells, including type I and type II pneumocytes, were the primary infected cells. Bacterial co-infections were identified in >25% of the case-patients. Viral pneumonia and immunolocalization of viral antigen in association with diffuse alveolar damage are prominent features of infection with 2009 pandemic influenza A (H1N1) virus. Underlying medical conditions and bacterial co-infections contributed to the fatal outcome of this infection. More studies are needed to understand the multifactorial pathogenesis of this infection.",,"['Shieh, Wun-Ju', 'Blau, Dianna M.', 'Denison, Amy M.', 'DeLeon-Carnes, Marlene', 'Adem, Patricia', 'Bhatnagar, Julu', 'Sumner, John', 'Liu, Lindy', 'Patel, Mitesh', 'Batten, Brigid', 'Greer, Patricia', 'Jones, Tara', 'Smith, Chalanda', 'Bartlett, Jeanine', 'Montague, Jeltley', 'White, Elizabeth', 'Rollin, Dominique', 'Gao, Rongbao', 'Seales, Cynthia', 'Jost, Heather', 'Metcalfe, Maureen', 'Goldsmith, Cynthia S.', 'Humphrey, Charles', 'Schmitz, Ann', 'Drew, Clifton', 'Paddock, Christopher', 'Uyeki, Timothy M.', 'Zaki, Sherif R.']",,,,
,PMC,The 2009 H1N1 Pandemic Adds to Our Knowledge of Influenza Pathogenesis,http://dx.doi.org/10.2353/ajpath.2010.100351,PMC2893645,,,This commentary discusses the pathology and pathogenesis of the 2009 H1N1 influenza A pandemic.,,"Walker, David H.",,,,
,PMC,Transfusion transmitted infections: How many more?,http://dx.doi.org/10.4103/0973-6247.67017,PMC2937299,20859502,CC BY,,2010 Jul,"Choudhury, Nabajyoti",Asian J Transfus Sci,,,
,PMC,Immunotherapy for non-small cell lung cancer,http://dx.doi.org/10.3816/CLC.2010.n.029,PMC3474196,,,"Developing effective immunotherapy for lung cancer is a daunting but hugely attractive challenge. Until recently, non-small cell lung cancer was thought of as a non-immunogenic tumor, but there is now evidence highlighting the integral role played by both inflammatory and immunological responses in lung carcinogenesis. Despite recent encouraging preclinical and phase I/II data, there is a paucity of phase III trials showing a clear clinical benefit for vaccines in lung cancer. There are many difficulties to overcome prior to the development of a successful therapy. Perhaps a measurable immune response may not translate into a clinically meaningful or radiological response. Patient selection may also be a problem for ongoing clinical studies. The majority of trials for lung cancer vaccines are focused on patients with advanced-stage disease, while the ideal candidates may be patients with a lower tumor burden stage I or II disease. Selecting the exact antigens to target is also difficult. It will likely require multiple epitopes of a diverse set of genes restricted to multiple haplotypes to generate a truly effective vaccine that is able to overcome the various immunologic escape mechanisms that tumors employ. This review discusses active immunotherapy employing protein/peptide vaccines, whole cell vaccines, and dendritic cell vaccines and examines the current data on some novel immunomodulating agents.",,"['Kelly, Ronan J.', 'Gulley, James L.', 'Giaccone, Giuseppe']",,,,
,PMC,A model for the biogenesis of turnip mosaic virus replication factories,,PMC2928320,,,"Nicotiana benthamiana plants were agroinfiltrated with an infectious clone of the Turnip mosaic virus (TuMV) that was engineered to tag replication vesicles with either GFP or mCherry fluorescent proteins. Punctuate vesicle structures were observed in the cytoplasm of infected cells corresponding to viral replication factories. The vesicles were highly motile and co-aligned with the microfilaments. Utilization of latrunculin B, an inhibitor of microfilament polymerization, reduced accumulation of the virus, suggesting that microfilaments are necessary during infection. To investigate biogenesis of the vesicles, leaves were infected simultaneously with two recombinant TuMV infectious clones, one that labeled vesicles in red and one that labeled them in green. We observed cell with green only and red only vesicles indicating a single viral genome origin. In some cases, vesicles exhibited sectors of green, red and yellow fluorescence were also observed, demonstrating that fusion among individual vesicles is possible. Based on those results we propose a model for the biogenesis of viral factory, where viral translation and replication are tightly coupled within virus-induced vesicles.",,"['Grangeon, Romain', 'Cotton, Sophie', 'Laliberté, Jean-François']",,,,
,PMC,DNA vaccines for targeting bacterial infections,http://dx.doi.org/10.1586/erv.10.57,PMC2962930,,,"DNA vaccination has been of great interest since its discovery in the 1990s due to its ability to elicit both humoral and cellular immune responses. DNA vaccines consist of a DNA plasmid containing a transgene that encodes the sequence of a target protein from a pathogen under the control of a eukaryotic promoter. This revolutionary technology has proven to be effective in animal models and four DNA vaccine products have recently been approved for veterinary use. Although few DNA vaccines against bacterial infections have been tested, the results are encouraging. Because of their versatility, safety and simplicity a wider range of organisms can be targeted by these vaccines, which shows their potential advantages to public health. This article describes the mechanism of action of DNA vaccines and their potential use for targeting bacterial infections. In addition, it provides an updated summary of the methods used to enhance immunogenicity from codon optimization and adjuvants to delivery techniques including electroporation and use of nanoparticles.",,"['Ingolotti, Mariana', 'Kawalekar, Omkar', 'Shedlock, Devon J', 'Muthumani, Karuppiah', 'Weiner, David B']",,,,
,PMC,Recovery from viral encephalomyelitis: immune-mediated noncytolytic virus clearance from neurons,http://dx.doi.org/10.1007/s12026-009-8143-4,PMC2891389,,,"Viral encephalomyelitis is caused by virus infections of neurons in the brain and spinal cord. Recovery is dependent on immune-mediated control and clearance of virus from these terminally differentiated essential cells. Preservation of neuronal function is essential for prevention of neurologic sequelae such as paralysis, seizures and cognitive deficits. Using the model system of Sindbis virus-induced encephalomyelitis in mice, we have shown that immune-mediated clearance of infectious virus from neurons is a noncytolytic process. The major effectors are antibody to the E2 surface glycoprotein produced by B cells, and interferon-γ produced by T cells. These effectors work in synergy, but neuronal populations differ in their responses to each. Virus is least likely to be cleared from brain neurons and most likely to be cleared from motor neurons in the cervical and thoracic regions of the spinal cord. Because the infected neurons are not eliminated, viral RNA persists and long-term control is needed to prevent virus reactivation. Virus-specific antibody-secreting cells residing in the nervous system after recovery from infection are likely to be important for long-term control.",,"Griffin, Diane E.",,,,
,PMC,Major histocompatibility complex class I binding predictions as a tool in epitope discovery,http://dx.doi.org/10.1111/j.1365-2567.2010.03300.x,PMC2913210,,,"Over the last decade, in silico models of the major histocompatibility complex (MHC) class I pathway have developed significantly. Before, peptide binding could only be reliably modelled for a few major human or mouse histocompatibility molecules; now, high-accuracy predictions are available for any human leucocyte antigen (HLA) -A or -B molecule with known protein sequence. Furthermore, peptide binding to MHC molecules from several non-human primates, mouse strains and other mammals can now be predicted. In this review, a number of different prediction methods are briefly explained, highlighting the most useful and historically important. Selected case stories, where these ‘reverse immunology’ systems have been used in actual epitope discovery, are briefly reviewed. We conclude that this new generation of epitope discovery systems has become a highly efficient tool for epitope discovery, and recommend that the less accurate prediction systems of the past be abandoned, as these are obsolete.",,"['Lundegaard, Claus', 'Lund, Ole', 'Buus, Søren', 'Nielsen, Morten']",,,,
,PMC,"Frequent Multidrug-Resistant Acinetobacter baumannii Contamination of Gloves, Gowns, and Hands of Healthcare Workers",http://dx.doi.org/10.1086/653201,PMC3010849,,,"BACKGROUND: Multidrug-resistant (MDR) gram-negative bacilli are important nosocomial pathogens. OBJECTIVE: To determine the incidence of transmission of MDR Acinetobacter baumannii and Pseudomonas aeruginosa from patients to healthcare workers (HCWs) during routine patient care. DESIGN: Prospective cohort study. SETTING: Medical and surgical intensive care units. METHODS: We observed HCWs who entered the rooms of patients colonized with MDR A. baumannii or colonized with both MDR A. baumannii and MDR P. aeruginosa. We examined their hands before room entry, their disposable gloves and/or gowns upon completion of patient care, and their hands after removal of gloves and/or gowns and before hand hygiene. RESULTS: Sixty-five interactions occurred with patients colonized with MDR A. baumannii and 134 with patients colonized with both MDR A. baumannii and MDR P. aeruginosa. Of 199 interactions between HCWs and patients colonized with MDR A. baumannii, 77 (38.7% [95% confidence interval {CI}, 31.9%–45.5%]) resulted in HCW contamination of gloves and/or gowns, and 9 (4.5% [95% CI, 1.6%–7.4%]) resulted in contamination of HCW hands after glove removal before hand hygiene. Of 134 interactions with patients colonized with MDR P. aeruginosa, 11 (8.2% [95% CI, 3.6%–12.9%]) resulted in HCW contamination of gloves and/or gowns, and 1 resulted in HCW contamination of hands. Independent risk factors for contamination with MDR A. baumannii were manipulation of wound dressing (adjusted odds ratio [aOR], 25.9 [95% CI, 3.1–208.8]), manipulation of artificial airway (aOR, 2.1 [95% CI, 1.1–4.0]), time in room longer than 5 minutes (aOR, 4.3 [95% CI, 2.0–9.1]), being a physician or nurse practitioner (aOR, 7.4 [95% CI, 1.6–35.2]), and being a nurse (aOR, 2.3 [95% CI, 1.1–4.8]). CONCLUSIONS: Gowns, gloves, and unwashed hands of HCWs were frequently contaminated with MDR A. baumannii. MDR A. baumannii appears to be more easily transmitted than MDR P. aeruginosa and perhaps more easily transmitted than previously studied methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococcus. This ease of transmission may help explain the emergence of MDR A. baumannii.",,"['Morgan, Daniel J.', 'Liang, Stephen Y.', 'Smith, Catherine L.', 'Johnson, J. Kristie', 'Harris, Anthony D.', 'Furuno, Jon P.', 'Thom, Kerri A.', 'Snyder, Graham M.', 'Day, Hannah R.', 'Perencevich, Eli N.']",,,,
,PMC,"Anesthesia with Intraperitoneal Propofol, Medetomidine, and Fentanyl in Rats",,PMC2919186,,,"A safe and reliable method for anesthetizing rats has long been a leading concern of biomedical researchers. We recently found that the intraperitoneal administration of propofol combined with medetomidine and fentanyl is safe for mouse anesthesia. Here we studied whether the same combination could be used for general anesthesia in rats. We used male Wistar rats to test 10 combinations of propofol, medetomidine, and fentanyl administered intraperitoneally and reversed with intraperitoneal atipamezole 30 min after induction. The depth of anesthesia, induction time, loss of pedal withdrawal reflex, pulse rate, and respiratory rate were evaluated, along with the duration and quality of induction, surgical anesthesia, and recovery. The combination of propofol and medetomidine provided a predictable induction and sufficient hypnosis and muscle relaxation, but surgical anesthesia (loss of pedal withdrawal reflex) was difficult to achieve with this protocol. The addition of fentanyl increased analgesia, making it possible to achieve surgical anesthesia. In conclusion, combination of propofol (100 mg/kg), medetomidine (0.1 mg/kg), and fentanyl (0.1 mg/kg) is a safe and practical technique for intraperitoneal anesthesia in rats, providing a surgical window of 25 min and restraint for 30 min, with rapid recovery after administration of atipamezole.",,"['Alves, Heber Nuno Castro', 'da Silva, Aura Luísa Maia', 'Olsson, Ingrid Anna S', 'Orden, José Manuel Gonzalo', 'Antunes, Luis Marques']",,,,
,PMC,National Athletic Trainers' Association Position Statement: Skin Diseases,http://dx.doi.org/10.4085/1062-6050-45.4.411,PMC2902037,,,"OBJECTIVE: To present recommendations for the prevention, education, and management of skin infections in athletes. BACKGROUND: Trauma, environmental factors, and infectious agents act together to continually attack the integrity of the skin. Close quarters combined with general poor hygiene practices make athletes particularly vulnerable to contracting skin diseases. An understanding of basic prophylactic measures, clinical features, and swift management of common skin diseases is essential for certified athletic trainers to aid in preventing the spread of infectious agents. RECOMMENDATIONS: These guidelines are intended to provide relevant information on skin infections and to give specific recommendations for certified athletic trainers and others participating in athletic health care.",,"['Zinder, Steven M.', 'Basler, Rodney S. W.', 'Foley, Jack', 'Scarlata, Chris', 'Vasily, David B.']",,,,
,PMC,Host-response biomarkers for diagnosis of late-onset septicemia and necrotizing enterocolitis in preterm infants,http://dx.doi.org/10.1172/JCI40196,PMC2912182,,,"Preterm infants are highly susceptible to life-threatening infections that are clinically difficult to detect, such as late-onset septicemia and necrotizing enterocolitis (NEC). Here, we used a proteomic approach to identify biomarkers for diagnosis of these devastating conditions. In a case-control study comprising 77 sepsis/NEC and 77 nonsepsis cases (10 in each group being monitored longitudinally), plasma samples collected at clinical presentation were assessed in the biomarker discovery and independent validation phases. We validated the discovered biomarkers in a prospective cohort study with 104 consecutively suspected sepsis/NEC episodes. Proapolipoprotein CII (Pro-apoC2) and a des-arginine variant of serum amyloid A (SAA) were identified as the most promising biomarkers. The ApoSAA score computed from plasma apoC2 and SAA concentrations was effective in identifying sepsis/NEC cases in the case-control and cohort studies. Stratification of infants into different risk categories by the ApoSAA score enabled neonatologists to withhold treatment in 45% and enact early stoppage of antibiotics in 16% of nonsepsis infants. The negative predictive value of this antibiotic policy was 100%. The ApoSAA score could potentially allow early and accurate diagnosis of sepsis/NEC. Upon confirmation by further multicenter trials, the score would facilitate rational prescription of antibiotics and target infants who require urgent treatment.",,"['Ng, Pak Cheung', 'Ang, Irene Ling', 'Chiu, Rossa Wai Kwun', 'Li, Karen', 'Lam, Hugh Simon', 'Wong, Raymond Pui On', 'Chui, Kit Man', 'Cheung, Hon Ming', 'Ng, Eddy Wing Yin', 'Fok, Tai Fai', 'Sung, Joseph Jao Yiu', 'Lo, Yuk Ming Dennis', 'Poon, Terence Chuen Wai']",,,,
,PMC,Population-based Post-crisis Psychological Distress: An Example From the SARS Outbreak in Taiwan,http://dx.doi.org/10.1016/S0929-6646(10)60087-3,PMC3106105,,,"BACKGROUND/PURPOSE: As a result of the severe acute respiratory syndrome (SARS) pandemic, the World Health Organization placed Taiwan on the travel alert list from May 21 to July 5, 2003. The aim of this study was to explore the post-crisis psychological distress among residents in Taiwan after the SARS epidemic. METHODS: The target population consisted of a nationwide representative sample of residents aged ≥ 18 years. Data were collected using computer assisted telephone interview systems by stratified random sampling according to geographic area. The survey (n = 1278) was conducted in November 2003, about 4 months after resolution of the SARS crisis in Taiwan. The maximum deviation of sampling error at the 95% confidence level was ± 2.74%. Psychological distress was measured by a question related to subject’s changes in perception of life, plus the five-item Brief Symptom Rating Scale. Multivariate logistic regression was used to examine the correlation of psychological distress. RESULTS: About 9.2% of the participants reported that their perceptions of life became more pessimistic following the SARS crisis. The prevalence of psychiatric morbidity was 11.7%. Major predictors of higher levels of pessimism after the SARS epidemic included demographic factors, perception of SARS and pre-paredness, knowing people or having personal experiences of SARS-related discrimination, and individual worries and psychiatric morbidity. The correlates of symptomatic cases, as indicated by the five-item Brief Symptom Rating Scale, included age ≥ 50 years, senior high school graduate, and worries about recurrence of SARS. CONCLUSION: Psychological distress was significantly correlated with demographic factors and perception regarding the SARS epidemic. It is suggested that marketing of mental health education should be segmented according to age and education level, which should enhance crisis communication for newly emerging infectious diseases among community populations.",,"['Peng, Eugene Yu-Chang', 'Lee, Ming-Been', 'Tsai, Shang-Ta', 'Yang, Chih-Chien', 'Morisky, Donald Edward', 'Tsai, Liang-Ting', 'Weng, Ya-Ling', 'Lyu, Shu-Yu']",,,,
,PMC,IMMUNITY AND IMMUNOPATHOLOGY TO VIRUSES: what decides the outcome?,http://dx.doi.org/10.1038/nri2802,PMC3899649,,,"Many viruses infect humans and most are controlled satisfactorily by the immune system with limited damage to host tissues. Some viruses, however, do cause overt damage to the host, either in isolated cases or as a reaction that commonly occurs after infection. The outcome is influenced by properties of the infecting virus, the circumstances of infection and multiple factors controlled by the host. In this Review, we focus on host factors that influence the outcome of viral infection, including genetic susceptibility, the age of the host when infected, the dose and route of infection, the induction of anti-inflammatory cells and proteins as well as the presence of concurrent infections and past exposure to cross-reactive agents.",,"['Rouse, Barry T.', 'Sehrawat, Sharvan']",,,,
,PMC,A modified MS2 bacteriophage plaque reduction assay for the rapid screening of antiviral plant extracts,http://dx.doi.org/10.4103/0974-8490.69108,PMC3141131,21808571,CC BY-NC-SA,"INTRODUCTION: Traditional methods of screening plant extracts and purified components for antiviral activity require up to a week to perform, prompting the need to develop more rapid quantitative methods to measure the ability of plant based preparations to block viral replication. We describe an adaption of an MS2 plaque reduction assay for use in S. aureus. RESULTS: MS2 bacteriophage was capable of infecting and replicating in B. cereus, S. aureus and F + E. coli but not F- E. coli. Indeed, both B. cereus and S. aureus were more sensitive to MS2 induced lysis than F+ E. coli. When MS2 bacteriophage was mixed with Camellia sinensis extract (1 mg/ml), Scaevola spinescens extract (1 mg/ml) or Aloe barbadensis juice and the mixtures inoculated into S. aureus, the formation of plaques was reduced to 8.9 ± 3.8%, 5.4 ± 2.4% and 72.7 ± 20.9% of the untreated MS2 control values respectively. CONCLUSIONS: The ability of the MS2 plaque reduction assay to detect antiviral activity in these known antiviral plant preparations indicates its suitability as an antiviral screening tool. An advantage of this assay compared with traditionally used cytopathic effect reduction assays and replicon based assays is the more rapid acquisition of results. Antiviral activity was detected within 24 h of the start of testing. The MS2 assay is also inexpensive and non-pathogenic to humans making it ideal for initial screening studies or as a simulant for pathogenic viruses.",2010 Jul-Aug,"['Cock, Ian', 'Kalt, F. R.']",Pharmacognosy Res,,,
,PMC,Spatial Analysis of Feline Immunodeficiency Virus Infection in Cougars,http://dx.doi.org/10.1016/j.sste.2010.03.009,PMC3010737,,,"The cougar (Puma concolor) is a large predatory feline found widely in the Americas that is susceptible to feline immunodeficiency virus (FIV), a fast-evolving lentivirus found in wild feline species that is analogous to simian immunodeficiency viruses in wild primates and belongs to the same family of viruses as human immunodeficiency virus. FIV infection in cougars can lead to a weakened immune system that creates opportunities for other infecting agents. FIV prevalence and lineages have been studied previously in several areas in the western United States, but typically without spatially explicit statistical techniques. To describe the distribution of FIV in a sample of cougars located in the northern Rocky Mountain region of North America, we first used kernel density ratio estimation to map the log relative risk of FIV. The risk surface showed a significant cluster of FIV in northwestern Montana. We also used Bayesian cluster models for genetic data to investigate the spatial structure of the feline immunodeficiency virus with virus genetic sequence data. A result of the models was two spatially distinct FIV lineages that aligned considerably with an interstate highway in Montana. Our results suggest that the use of spatial information and models adds novel insight when investigating an infectious animal disease. The results also suggest that the influence of landscape features likely plays an important role in the spatiotemporal spread of an infectious disease within wildlife populations.",,"['Wheeler, David C.', 'Waller, Lance A.', 'Biek, Roman']",,,,
,PMC,Controlling subcellular delivery to optimize therapeutic effect,,PMC2989634,,,"This article focuses on drug targeting to specific cellular organelles for therapeutic purposes. Drugs can be delivered to all major organelles of the cell (cytosol, endosome/lysosome, nucleus, nucleolus, mitochondria, endoplasmic reticulum, Golgi apparatus, peroxisomes and proteasomes) where they exert specific effects in those particular subcellular compartments. Delivery can be achieved by chemical (e.g., polymeric) or biological (e.g., signal sequences) means. Unidirectional targeting to individual organelles has proven to be immensely successful for drug therapy. Newer technologies that accommodate multiple signals (e.g., protein switch and virus-like delivery systems) mimic nature and allow for a more sophisticated approach to drug delivery. Harnessing different methods of targeting multiple organelles in a cell will lead to better drug delivery and improvements in disease therapy.",,"['Mossalam, Mohanad', 'Dixon, Andrew S', 'Lim, Carol S']",,,,
,PMC,Detection of respiratory viruses and the associated chemokine responses in serious acute respiratory illness,http://dx.doi.org/10.1136/thx.2009.132480,PMC3018337,,,"BACKGROUND: A specific diagnosis of a lower respiratory viral infection is often difficult despite frequent clinical suspicion. This low diagnostic yield may be improved by use of sensitive detection methods and biomarkers. METHODS: We investigated the prevalence, clinical predictors and inflammatory mediator profile of respiratory viral infection in serious acute respiratory illness. Sequential bronchoalveolar lavage (BAL) fluids from all patients hospitalized with acute respiratory illness over 12 months (n=283) were tested for the presence of 17 respiratory viruses by multiplex PCR assay and for newly-discovered respiratory viruses (bocavirus, WU and KI polyomaviruses) by single-target PCR. BAL samples also underwent conventional testing (direct immunoflorescence and viral culture) for respiratory virus at the clinician’s discretion. 27 inflammatory mediators were measured in subset of the patients (n=64) using a multiplex immunoassay. RESULTS: We detected 39 respiratory viruses in 37 (13.1% of total) patients by molecular testing, including rhinovirus (n=13), influenza virus (n=8), respiratory syncytial virus (n=6), human metapneumovirus (n=3), coronavirus NL63 (n=2), parainfluenza virus (n=2), adenovirus (n=1), and newly-discovered viruses (n=4). Molecular methods were 3.8-fold more sensitive than conventional methods. Clinical characteristics alone were insufficient to separate patients with and without respiratory virus. The presence of respiratory virus was associated with increased levels of interferon-γ-inducible protein 10 (IP -10)(p<0.001) and eotaxin-1 (p=0.017) in BAL. CONCLUSIONS: Respiratory viruses can be found in patients with serious acute respiratory illness by use of PCR assays more frequently than previously appreciated. IP-10 may be a useful biomarker for respiratory viral infection.",,"['Sumino, Kaharu C.', 'Walter, Michael J.', 'Mikols, Cassandra L.', 'Thompson, Samantha A.', 'Gaudreault-Keener, Monique', 'Arens, Max. Q.', 'Agapov, Eugene', 'Hormozdi, David', 'Gaynor, Anne M.', 'Holtzman, Michael J.', 'Storch, Gregory A.']",,,,
,PMC,Bovine Respiratory Coronavirus,http://dx.doi.org/10.1016/j.cvfa.2010.04.005,PMC4094360,,,,,"Saif, Linda J.",,,,
,PMC,Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein,http://dx.doi.org/10.1016/j.virol.2010.05.031,PMC2914208,,,"Coronaviruses are enveloped RNA viruses that generally cause mild disease in humans. However, the recently emerged coronavirus that caused severe acute respiratory syndrome (SARS-CoV) is the most pathogenic human coronavirus discovered to date. The SARS-CoV spike (S) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. Coronavirus S proteins are palmitoylated, which may affect function. Here, we created a non-palmitoylated SARS-CoV S protein by mutating all nine cytoplasmic cysteine residues. Palmitoylation of SARS-CoV S was required for partitioning into detergent-resistant membranes and for cell-cell fusion. Surprisingly, however, palmitoylation of S was not required for interaction with SARS-CoV M protein. This contrasts with the requirement for palmitoylation of mouse hepatitis virus S protein for interaction with M protein, and may point to important differences in assembly and infectivity of these two coronaviruses.",,"['McBride, Corrin E.', 'Machamer, Carolyn E.']",,,,
,PMC,SNARE motif: A common motif used by pathogens to manipulate membrane fusion,http://dx.doi.org/10.4161/viru.1.4.12195,PMC3073298,,,"To penetrate host cells through their membranes, pathogens use a variety of molecular components in which the presence of heptad repeat motifs seems to be a prevailing element. Heptad repeats are characterized by a pattern of seven, generally hydrophobic, residues. In order to initiate membrane fusion, viruses use glycoproteins-containing heptad repeats. These proteins are structurally and functionally similar to the SNARE proteins known to be involved in eukaryotic membrane fusion. SNAREs also display a heptad repeat motif called the “SNARE motif”. As bacterial genomes are being sequenced, microorganisms also appear to be carrying membrane proteins resembling eukaryotic SNAREs. This category of SNARE-like proteins might share similar functions and could be used by microorganisms to either promote or block membrane fusion. Such a recurrence across pathogenic organisms suggests that this architectural motif was evolutionarily selected because it most effectively ensures the survival of pathogens within the eukaryotic environment.",,"['Wesolowski, Jordan', 'Paumet, Fabienne']",,,,
,PMC,Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature,http://dx.doi.org/10.1152/ajpcell.00047.2010,PMC2944325,,,"There must be something unique about a class of drugs (discovered and developed in the mid-1940s) where there are more than 130 ongoing clinical trials currently listed. Tetracyclines were developed as a result of the screening of soil samples for antibiotic organisms. The first of these compounds chlortetracycline was introduced in 1948. Soon after their development tetracyclines were found to be highly effective against various pathogens including rickettsiae, Gram-positive, and Gram-negative bacteria, thus, becoming a class of broad-spectrum antibiotics. The mechanism of action of tetracyclines is thought to be related to the inhibition of protein synthesis by binding to the 30S bacterial ribosome. Tetracyclines are also an effective anti-malarial drug. Over time, many other “protective” actions have been described for tetracyclines. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Its mechanism of action appears to relate to specific effects exerted on apoptosis signaling pathways. Another tetracycline, doxycycline is known to exert antiprotease activities. Doxycycline can inhibit matrix metalloproteinases, which contribute to tissue destruction activities in diseases such as gingivitis. A large body of literature has provided additional evidence for the “beneficial” actions of tetracyclines, including their ability to act as oxygen radical scavengers and anti-inflammatory agents. This increasing volume of published work and ongoing clinical trials supports the notion that a more systematic examination of their possible therapeutic uses is warranted. This review provides a summary of tetracycline's multiple mechanisms of action and while using the effects on the heart as an example, this review also notes their potential to benefit patients suffering from various pathologies such as cancer, Rosacea, and Parkinson's disease.",,"['Griffin, Michael O.', 'Fricovsky, Eduardo', 'Ceballos, Guillermo', 'Villarreal, Francisco']",,,,
,PMC,Frequency of Detection of Upper Respiratory Tract Viruses in Patients Tested for Pandemic H1N1/09 Viral Infection,http://dx.doi.org/10.1128/JCM.01179-10,PMC2937695,,,"Molecular testing of 270 consecutive nasopharyngeal swab samples taken in May and June 2009 and 274 samples from patients hospitalized between July and December 2009 showed similar findings of respiratory viruses, with influenza A pandemic virus H1N1/09 being the most represented, followed by human parainfluenza virus type 3 and rhinoviruses. Statistical analyses suggested virus cocirculation in the absence of viral interference.",,"['Nisii, Carla', 'Meschi, Silvia', 'Selleri, Marina', 'Bordi, Licia', 'Castilletti, Concetta', 'Valli, Maria Beatrice', 'Lalle, Eleonora', 'Lauria, Francesco Nicola', 'Piselli, Pierluca', 'Lanini, Simone', 'Ippolito, Giuseppe', 'Di Caro, Antonino', 'Capobianchi, Maria Rosaria']",,,,
,PMC,Bepridil and Amiodarone Simultaneously Target the Alzheimer's Disease β- and γ-Secretase via Distinct Mechanisms,http://dx.doi.org/10.1523/JNEUROSCI.1199-10.2010,PMC6632893,,,"The two proteases β-secretase and γ-secretase generate the amyloid β peptide and are drug targets for Alzheimer's disease. Here we tested the possibility of targeting the cellular environment of β-secretase cleavage instead of the β-secretase enzyme itself. β-Secretase has an acidic pH optimum and cleaves the amyloid precursor protein in the acidic endosomes. We identified two drugs, bepridil and amiodarone, that are weak bases and are in clinical use as calcium antagonists. Independently of their calcium-blocking activity, both compounds mildly raised the membrane-proximal, endosomal pH and inhibited β-secretase cleavage at therapeutically achievable concentrations in cultured cells, in primary neurons, and in vivo in guinea pigs. This shows that an alkalinization of the cellular environment could be a novel therapeutic strategy to inhibit β-secretase. Surprisingly, bepridil and amiodarone also modulated γ-secretase cleavage independently of endosomal alkalinization. Thus, both compounds act as dual modulators that simultaneously target β- and γ-secretase through distinct molecular mechanisms. In addition to Alzheimer's disease, compounds with dual properties may also be useful for drug development targeting other membrane proteins.",,"['Mitterreiter, Stefan', 'Page, Richard M.', 'Kamp, Frits', 'Hopson, Jessika', 'Winkler, Edith', 'Ha, Huy-Riem', 'Hamid, Runa', 'Herms, Jochen', 'Mayer, Thomas U.', 'Nelson, Deborah J.', 'Steiner, Harald', 'Stahl, Tobias', 'Zeitschel, Ulrike', 'Roßner, Steffen', 'Haass, Christian', 'Lichtenthaler, Stefan F.']",,,,
,PMC,RNA 5′-Triphosphatase Activity of the Hepatitis E Virus Helicase Domain,http://dx.doi.org/10.1128/JVI.00492-10,PMC2937651,,,"Hepatitis E virus (HEV) has a positive-sense RNA genome with a 5′-m7G cap. HEV open reading frame 1 (ORF1) encodes a polyprotein with multiple enzyme domains required for replication. HEV helicase is a nucleoside triphosphatase (NTPase) with the ability to unwind RNA duplexes in the 5′-to-3′ direction. When incubated with 5′-[γ-(32)P]RNA and 5′-[α-(32)P]RNA, HEV helicase released (32)P only from 5′-[γ-(32)P]RNA, showing specificity for the γ-β-triphosphate bond. Removal of γ-phosphate from the 5′ end of the primary transcripts (pppRNA to ppRNA) by RNA triphosphatase is an essential step during cap formation. It is suggested that HEV employs the helicase to mediate the first step of 5′ cap synthesis.",,"['Karpe, Yogesh A.', 'Lole, Kavita S.']",,,,
,PMC,Memory CD4 T Cells Direct Protective Responses to Influenza Virus in the Lungs through Helper-Independent Mechanisms,http://dx.doi.org/10.1128/JVI.01069-10,PMC2937635,,,"Memory CD4 T cells specific for influenza virus are generated from natural infection and vaccination, persist long-term, and recognize determinants in seasonal and pandemic influenza virus strains. However, the protective potential of these long-lived influenza virus-specific memory CD4 T cells is not clear, including whether CD4 T-cell helper or effector functions are important in secondary antiviral responses. Here we demonstrate that memory CD4 T cells specific for H1N1 influenza virus directed protective responses to influenza virus challenge through intrinsic effector mechanisms, resulting in enhanced viral clearance, recovery from sublethal infection, and full protection from lethal challenge. Mice with influenza virus hemagglutinin (HA)-specific memory CD4 T cells or polyclonal influenza virus-specific memory CD4 T cells exhibited protection from influenza virus challenge that occurred in the presence of CD8-depleting antibodies in B-cell-deficient mice and when CD4 T cells were transferred into lymphocyte-deficient RAG2(−/−) mice. Moreover, the presence of memory CD4 T cells mobilized enhanced T-cell recruitment and immune responses in the lung. Neutralization of gamma interferon (IFN-γ) production in vivo abrogated memory CD4 T-cell-mediated protection from influenza virus challenge by HA-specific memory T cells and heterosubtypic protection by polyclonal memory CD4 T cells. Our results indicate that memory CD4 T cells can direct enhanced protection from influenza virus infection through mobilization of immune effectors in the lung, independent of their helper functions. These findings have important implications for the generation of universal influenza vaccines by promoting long-lived protective CD4 T-cell responses.",,"['Teijaro, John R.', 'Verhoeven, David', 'Page, Carly A.', 'Turner, Damian', 'Farber, Donna L.']",,,,
,PMC,Exotic effects of capital accumulation,http://dx.doi.org/10.1073/pnas.1007335107,PMC2901458,,,,,"Perrings, Charles",,,,
,PMC,Construction and characterization of calreticulin-HBsAg fusion gene recombinant adenovirus expression vector,http://dx.doi.org/10.3748/wjg.v16.i24.3078,PMC2890950,,,"AIM: To generate recombinant adenoviral vector containing calreticulin (CRT)-hepatitis B surface antigen (HBsAg) fusion gene for developing a safe, effective and HBsAg-specific therapeutic vaccine. METHODS: CRT and HBsAg gene were fused using polymerase chain reaction (PCR), endonuclease digestion and ligation methods. The fusion gene was cloned into pENTR/D-TOPO transfer vector after the base pairs of DNA (CACC) sequence was added to the 5′ end. Adenoviral expression vector containing CRT-HBsAg fusion gene was constructed by homologous recombinantion. The human embryo kidney (HEK) 293A cells were transfected with linearized DNA plasmid of the recombinant adenoviral vector to package and amplify recombinant adenovirus. The recombinant adenovirus titer was characterized using the end-dilution assay. The expression of the CRT/HBsAg fusion protein in Ad-CRT/HBsAg infected 293A cells was detected by Western blotting. RESULTS: The CRT-HBsAg fusion gene was characterized by PCR and sequencing and its length and sequence were confirmed to be accurate. The CRT-HBsAg fusion gene recombinant pENTR/D-TOPO transfer vector was constructed. The recombinant adenoviral vector, Ad-CRT/HBsAg, was generated successfully. The titer of Ad-CRT/HBsAg was characterized as 3.9 × 10(11) pfu/mL. The CRT-HBsAg fusion protein was expressed by HEK 293A cells correctly. CONCLUSION: CRT/HBsAg fusion gene recombinant replication-defective adenovirus expression vector is constructed successfully and this study has provided an experimental basis for further studies of Hepatitis B virus gene therapy.",,"['Ma, Chun-Ling', 'Wang, Gui-Bin', 'Gu, Run-Guo', 'Wang, Fang']",,,,
,PMC,An allosteric inhibitor of substrate recognition by the SCF(Cdc4) ubiquitin ligase,http://dx.doi.org/10.1038/nbt.1646,PMC4445864,,,"The SCF ubiquitin ligases target proteins for degradation by recruitment factors called F-box proteins(1, 2). We identified a bi-planar dicarboxylic acid compound, called SCF-I2, as an inhibitor of substrate phosphodegron recognition by the yeast F-box protein Cdc4. SCF-I2 inhibits the binding and ubiquitination of full length phosphorylated substrates by SCF(Cdc4). A crystal co-structure reveals that SCF-I2 inserts between the β-strands of blades 5 and 6 of the WD40 propeller domain of Cdc4 at a site that is 25 Å remote from the substrate binding site. Long-range transmission of SCF-I2 interactions distorts the substrate binding pocket and impedes recognition of key determinants in the Cdc4 phosphodegron. Mutation of the SCF-I2 binding site abrogates its inhibitory effect and explains specificity in the allosteric inhibition mechanism. Mammalian WD40 domain proteins may exhibit similar allosteric responsiveness and hence represent an extensive new class of druggable target.",,"['Orlicky, Stephen', 'Tang, Xiaojing', 'Neduva, Victor', 'Elowe, Nadine', 'Brown, Eric', 'Sicheri, Frank', 'Tyers, Mike']",,,,
,PMC,Combining mathematics and empirical data to predict emergence of RNA viruses that differ in reservoir use,http://dx.doi.org/10.1098/rstb.2010.0075,PMC2880119,,,"RNA viruses may be particularly capable of contributing to the increasing biomedical problem of infectious disease emergence. Empirical studies and epidemiological models are informative for the understanding of evolutionary processes that promote pathogen emergence, but rarely are these approaches combined in the same study. Here, we used an epidemiology model containing observations of pathogen productivity in reservoirs, as a means to predict which pathogens should be most prone to emerge in a primary host such as humans. We employed as a model system a collection of vesicular stomatitis virus populations that had previously diverged in host-use strategy: specialists, directly selected generalists and indirectly selected (fortuitous) generalists. Using data from experiments where these viral strategists were challenged to grow on unencountered novel hosts in vitro, logistic growth models determined that the directly selected generalist viruses tended to grow best on model reservoirs. Furthermore, when we used the growth data to estimate average reproductive rate across secondary reservoirs, we showed that the combined approach could be used to estimate relative success of the differing virus strategists when encountering a primary host. Our study suggests that synergistic approaches combining epidemiological modelling with empirical data from experimental evolution may be useful for developing efforts to predict which types of pathogens pose the greatest probability of emerging in the future.",,"['Ogbunugafor, C. Brandon', 'Basu, Sanjay', 'Morales, Nadya M.', 'Turner, Paul E.']",,,,
,PMC,Lifestyles of plant viruses,http://dx.doi.org/10.1098/rstb.2010.0057,PMC2880111,,,"The vast majority of well-characterized eukaryotic viruses are those that cause acute or chronic infections in humans and domestic plants and animals. However, asymptomatic persistent viruses have been described in animals, and are thought to be sources for emerging acute viruses. Although not previously described in these terms, there are also many viruses of plants that maintain a persistent lifestyle. They have been largely ignored because they do not generally cause disease. The persistent viruses in plants belong to the family Partitiviridae or the genus Endornavirus. These groups also have members that infect fungi. Phylogenetic analysis of the partitivirus RNA-dependent RNA polymerase genes suggests that these viruses have been transmitted between plants and fungi. Additional families of viruses traditionally thought to be fungal viruses are also found frequently in plants, and may represent a similar scenario of persistent lifestyles, and some acute or chronic viruses of crop plants may maintain a persistent lifestyle in wild plants. Persistent, chronic and acute lifestyles of plant viruses are contrasted from both a functional and evolutionary perspective, and the potential role of these lifestyles in host evolution is discussed.",,"Roossinck, Marilyn J.",,,,
,PMC,Adaptation of tobacco etch potyvirus to a susceptible ecotype of Arabidopsis thaliana capacitates it for systemic infection of resistant ecotypes,http://dx.doi.org/10.1098/rstb.2010.0044,PMC2880108,,,"Viral pathogens continue to emerge among humans, domesticated animals and cultivated crops. The existence of genetic variance for resistance in the host population is crucial to the spread of an emerging virus. Models predict that rapid spread decreases with the frequency and diversity of resistance alleles in the host population. However, empirical tests of this hypothesis are scarce. Arabiodpsis thaliana—tobacco etch potyvirus (TEV) provides an experimentally suitable pathosystem to explore the interplay between genetic variation in host's susceptibility and virus diversity. Systemic infection of A. thaliana with TEV is controlled by three dominant loci, with different ecotypes varying in susceptibility depending on the genetic constitution at these three loci. Here, we show that the TEV adaptation to a susceptible ecotype allowed the virus to successfully infect, replicate and induce symptoms in ecotypes that were fully resistant to the ancestral virus. The value of these results is twofold. First, we showed that the existence of partially susceptible individuals allows for the emerging virus to bypass resistance alleles that the virus has never encountered. Second, the concept of resistance genes may only be valid for a well-defined viral genotype but not for polymorphic viral populations.",,"['Lalić, Jasna', 'Agudelo-Romero, Patricia', 'Carrasco, Purificación', 'Elena, Santiago F.']",,,,
,PMC,Autophagy protein ATG5 interacts transiently with the hepatitis C virus RNA polymerase (NS5B) early during infection,http://dx.doi.org/10.1016/j.virol.2010.05.032,PMC2925245,,,"Autophagy is an important cellular process by which ATG5 initiates the formation of double membrane vesicles (DMVs). Upon infection, DMVs have been shown to harbor the replicase complex of positive-strand RNA viruses such as MHV, poliovirus, and equine arteritis virus. Recently, it has been shown that autophagy proteins are proviral factors that favor initiation of hepatitis C virus (HCV) infection. Here, we identified ATG5 as an interacting protein for the HCV NS5B. ATG5/NS5B interaction was confirmed by co-IP and metabolic labeling studies. Furthermore, ATG5 protein colocalizes with NS4B, a constituent of the membranous web. Importantly, immunofluorescence staining demonstrated a strong colocalization of ATG5 and NS5B within perinuclear regions of infected cells at 2 days postinfection. However, colocalization was completely lacking at 5 DPI, suggesting that HCV utilizes ATG5 as a proviral factor during the onset of viral infection. Finally, inhibition of autophagy through ATG5 silencing blocks HCV replication.",,"['Guévin, Carl', 'Manna, David', 'Bélanger, Claudia', 'Konan, Kouacou V.', 'Mak, Paul', 'Labonté, Patrick']",,,,
,PMC,The Angiotensin-Converting Enzyme 2/Angiogenesis-(1–7)/Mas Axis Confers Cardiopulmonary Protection against Lung Fibrosis and Pulmonary Hypertension,http://dx.doi.org/10.1164/rccm.200912-1840OC,PMC2970847,,,"Rationale: An activated vasoconstrictive, proliferative, and fibrotic axis of the renin angiotensin system (angiotensin-converting enzyme [ACE]/angiotensin [Ang]II/AngII type 1 receptor) has been implicated in the pathophysiology of pulmonary fibrosis (PF) and pulmonary hypertension (PH). The recent discovery of a counterregulatory axis of the renin angiotensin system composed of ACE2/Ang-(1–7)/Mas has led us to examine the role of this vasoprotective axis on such disorders. Objectives: We hypothesized that Ang-(1–7) treatment would exert protective effects against PF and PH. Methods: Lentiviral packaged Ang-(1–7) fusion gene or ACE2 cDNA was intratracheally administered into the lungs of male Sprague Dawley rats. Two weeks after gene transfer, animals received bleomycin (2.5 mg/kg). In a subsequent study, animals were administered monocrotaline (MCT, 50 mg/kg). Measurements and Main Results: In the PF study, bleomycin administration resulted in a significant increase in right ventricular systolic pressure, which was associated with the development of right ventricular hypertrophy. The lungs of these animals also exhibited excessive collagen deposition, decreased expression of ACE and ACE2, increased mRNA levels for transforming growth factor β and other proinflammatory cytokines, and increased protein levels of the AT(1)R. Overexpression of Ang-(1–7) significantly prevented all the above-mentioned pathophysiological conditions. Similar protective effects were also obtained with ACE2 overexpression. In the PH study, rats injected with MCT developed elevated right ventricular systolic pressure, right ventricular hypertrophy, right ventricular fibrosis, and pulmonary vascular remodeling, all of which were attenuated by Ang-(1–7) overexpression. Blockade of the Mas receptor abolished the beneficial effects of Ang-(1–7) against MCT-induced PH. Conclusions: Our observations demonstrate a cardiopulmonary protective role for the ACE2/Ang-(1–7)/Mas axis in the treatment of lung disorders.",,"['Shenoy, Vinayak', 'Ferreira, Anderson J.', 'Qi, Yanfei', 'Fraga-Silva, Rodrigo A.', 'Díez-Freire, Carlos', 'Dooies, Autumn', 'Jun, Joo Yun', 'Sriramula, Srinivas', 'Mariappan, Nithya', 'Pourang, Dorna', 'Venugopal, Changaram S.', 'Francis, Joseph', 'Reudelhuber, Timothy', 'Santos, Robson A.', 'Patel, Jawaharlal M.', 'Raizada, Mohan K.', 'Katovich, Michael J.']",,,,
,PMC,Epidemiologic Approaches to Global Health,http://dx.doi.org/10.1093/epirev/mxq007,PMC2941737,,,"In this introduction to volume 32 of Epidemiologic Reviews, the authors highlight the diversity and complexity of global health concerns, and they frame the 12 articles included in this issue within the diverse topics of research in this emerging and ever-expanding field. The authors emphasize the need for ongoing research related to the methods used in global health and for comprehensive surveillance, and they offer suggestions for future directions in global health research.",,"['Quinn, Thomas C.', 'Samet, Jonathan M.']",,,,
,PMC,TNF-α-dependent regulation of CXCR3 expression modulates neuronal survival during West Nile virus encephalitis,http://dx.doi.org/10.1016/j.jneuroim.2010.05.003,PMC2910216,,,"The chemokine CXCL10 exerts antiviral effects within the central nervous system (CNS) through the recruitment of virus-specific T cells. However, elevated levels of CXCL10 may induce neuronal apoptosis given its receptor, CXCR3, is expressed by neurons. Using a murine model of West Nile virus (WNV) encephalitis, we determined that WNV-infected neurons express TNF-α, which down-regulates neuronal CXCR3 expression via signaling through TNFR1. Down-regulation of neuronal CXCR3 decreased CXCL10-mediated calcium transients and delayed Caspase 3 activation. Loss of CXCR3 activation, via CXCR3-deficiency or pretreatment with TNF-α prevented neuronal apoptosis during in vitro WNV infection. These results suggest that neuronal TNF-α expression during WNV encephalitis may be an adaptive response to diminish CXCL10-induced death.",,"['Zhang, Bo', 'Patel, Jigisha', 'Croyle, Michelle', 'Diamond, Michael S.', 'Klein, Robyn S.']",,,,
,PMC,Anterior Segment Mechanisms of Protection During HSV-1 Infection,http://dx.doi.org/10.1007/s10384-010-0798-9,PMC4021309,,,,,"['Atherton, Sally S.', 'Cathcart, Heather M.']",,,,
,PMC,Crystallization and preliminary X-ray diffraction analysis of the N-terminal domain of human coronavirus OC43 nucleocapsid protein,http://dx.doi.org/10.1107/S1744309110017616,PMC2898469,,,"The N-terminal domain of nucleocapsid protein from human coronavirus OC43 (HCoV-OC43 N-NTD) mostly contains positively charged residues and has been identified as being responsible for RNA binding during ribonucleocapsid formation in the coronavirus. In this study, the crystallization and preliminary crystallographic analysis of HCoV-OC43 N-NTD (amino acids 58–195) with a molecular weight of 20 kDa are reported. HCoV-OC43 N-NTD was crystallized at 293 K using PEG 1500 as a precipitant and a 99.9% complete native data set was collected to 1.7 Å resolution at 100 K with an overall R (merge) of 5.0%. The crystals belonged to the hexagonal space group P6(5), with unit-cell parameters a = 81.57, c = 42.87 Å. Solvent-content calculations suggest that there is likely to be one subunit of N-NTD in the asymmetric unit.",,"['Chen, I-Jung', 'Chou, Chia-Cheng', 'Liu, Chia-Ling', 'Lee, Cheng-Chung', 'Kan, Lou-Sing', 'Hou, Ming-Hon']",,,,
,PMC,Heat Shock Protein 70 (Hsp70) as an Emerging Drug Target,http://dx.doi.org/10.1021/jm100054f,PMC2895966,,,,,"['Evans, Christopher G.', 'Chang, Lyra', 'Gestwicki, Jason E.']",,,,
,PMC,A Single Asparagine-Linked Glycosylation Site of the Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Facilitates Inhibition by Mannose-Binding Lectin through Multiple Mechanisms,http://dx.doi.org/10.1128/JVI.00554-10,PMC2919028,,,"Mannose-binding lectin (MBL) is a serum protein that plays an important role in host defenses as an opsonin and through activation of the complement system. The objective of this study was to assess the interactions between MBL and severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) glycoprotein (SARS-S). MBL was found to selectively bind to retroviral particles pseudotyped with SARS-S. Unlike several other viral envelopes to which MBL can bind, both recombinant and plasma-derived human MBL directly inhibited SARS-S-mediated viral infection. Moreover, the interaction between MBL and SARS-S blocked viral binding to the C-type lectin, DC-SIGN. Mutagenesis indicated that a single N-linked glycosylation site, N330, was critical for the specific interactions between MBL and SARS-S. Despite the proximity of N330 to the receptor-binding motif of SARS-S, MBL did not affect interactions with the ACE2 receptor or cathepsin L-mediated activation of SARS-S-driven membrane fusion. Thus, binding of MBL to SARS-S may interfere with other early pre- or postreceptor-binding events necessary for efficient viral entry.",,"['Zhou, Yanchen', 'Lu, Kai', 'Pfefferle, Susanne', 'Bertram, Stephanie', 'Glowacka, Ilona', 'Drosten, Christian', 'Pöhlmann, Stefan', 'Simmons, Graham']",,,,
,PMC,Visualizing the Replication Cycle of Bunyamwera Orthobunyavirus Expressing Fluorescent Protein-Tagged Gc Glycoprotein,http://dx.doi.org/10.1128/JVI.00902-10,PMC2919021,,,"The virion glycoproteins Gn and Gc of Bunyamwera virus (BUNV), the prototype of the Bunyaviridae family and also of the Orthobunyavirus genus, are encoded by the medium (M) RNA genome segment and are involved in both viral attachment and entry. After their synthesis Gn and Gc form a heterodimer in the endoplasmic reticulum (ER) and transit to the Golgi compartment for virus assembly. The N-terminal half of the Gc ectodomain was previously shown to be dispensable for virus replication in cell culture (X. Shi, J. Goli, G. Clark, K. Brauburger, and R. M. Elliott, J. Gen. Virol. 90:2483-2492, 2009.). In this study, the coding sequence for a fluorescent protein, either enhanced green fluorescent protein (eGFP) or mCherry fluorescent protein, was fused to the N terminus of truncated Gc, and two recombinant BUNVs (rBUNGc-eGFP and rBUNGc-mCherry) were rescued by reverse genetics. The recombinant viruses showed bright autofluorescence under UV light and were competent for replication in various mammalian cell lines. rBUNGc-mCherry was completely stable over 10 passages, whereas internal, in-frame deletions occurred in the chimeric Gc-eGFP protein of rBUNGc-eGFP, resulting in loss of fluorescence between passages 5 and 7. Autofluorescence of the recombinant viruses allowed visualization of different stages of the infection cycle, including virus attachment to the cell surface, budding of virus particles in Golgi membranes, and virus-induced morphological changes to the Golgi compartment at later stages of infection. The fluorescent protein-tagged viruses will be valuable reagents for live-cell imaging studies to investigate virus entry, budding, and morphogenesis in real time.",,"['Shi, Xiaohong', 'van Mierlo, Joël T.', 'French, Andrew', 'Elliott, Richard M.']",,,,
,PMC,The Cellular RNA Helicase DDX1 Interacts with Coronavirus Nonstructural Protein 14 and Enhances Viral Replication,http://dx.doi.org/10.1128/JVI.00392-10,PMC2918985,,,"The involvement of host proteins in the replication and transcription of viral RNA is a poorly understood area for many RNA viruses. For coronaviruses, it was long speculated that replication of the giant RNA genome and transcription of multiple subgenomic mRNA species by a unique discontinuous transcription mechanism may require host cofactors. To search for such cellular proteins, yeast two-hybrid screening was carried out by using the nonstructural protein 14 (nsp14) from the coronavirus infectious bronchitis virus (IBV) as a bait protein, leading to the identification of DDX1, a cellular RNA helicase in the DExD/H helicase family, as a potential interacting partner. This interaction was subsequently confirmed by coimmunoprecipitation assays with cells coexpressing the two proteins and with IBV-infected cells. Furthermore, the endogenous DDX1 protein was found to be relocated from the nucleus to the cytoplasm in IBV-infected cells. In addition to its interaction with IBV nsp14, DDX1 could also interact with the nsp14 protein from severe acute respiratory syndrome coronavirus (SARS-CoV), suggesting that interaction with DDX1 may be a general feature of coronavirus nsp14. The interacting domains were mapped to the C-terminal region of DDX1 containing motifs V and VI and to the N-terminal portion of nsp14. Manipulation of DDX1 expression, either by small interfering RNA-induced knockdown or by overexpression of a mutant DDX1 protein, confirmed that this interaction may enhance IBV replication. This study reveals that DDX1 contributes to efficient coronavirus replication in cell culture.",,"['Xu, Linghui', 'Khadijah, Siti', 'Fang, Shouguo', 'Wang, Li', 'Tay, Felicia P. L.', 'Liu, Ding Xiang']",,,,
,PMC,Protective effects of luteolin against lipopolysaccharide-induced acute lung injury involves inhibition of MEK/ERK and PI3K/Akt pathways in neutrophils,http://dx.doi.org/10.1038/aps.2010.62,PMC4007725,,,"AIM: To investigate whether luteolin, the major polyphenolic components of Lonicera japonica, has beneficial effects against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and to determine whether the protective mechanism involves anti-inflammatory effects on neutrophils. METHODS: ALI was induced with intratracheal instillation of LPS in mice. The level of ALI was determined by measuring the cell count and protein content in bronchoalveolar lavage (BAL) fluid. Neutrophils were stimulated with formyl-Met-Leu-Phe (fMLP) or LPS in vitro. Chemotaxis and superoxide anion generation were measured to evaluate neutrophil activation. The potential involvement of intracellular signaling molecules in regulating neutrophil activation was analyzed by using Western blot. RESULTS: LPS induced ALI in mice, as evidenced with leukocyte infiltration and protein leakage into the lungs. Luteolin attenuated LPS-induced leukocyte infiltration and protein extravasation. In cell studies, luteolin attenuated the fMLP-induced neutrophil chemotaxis and respiratory burst (IC(50) 0.2±0.1 μmol/L and 2.2±0.8 μmol/L, respectively), but had a negligible effect on superoxide anion generation during phorbol myristate acetate stimulation. Furthermore luteolin effectively blocked MAPK/ERK kinase 1/2 (MEK), extracellular signal-regulated kinase (ERK), and Akt phosphorylation in fMLP- and LPS-stimulated neutrophils. CONCLUSION: These results indicate that luteolin has beneficial effects against LPS-induced ALI in mice, and the attenuation of neutrophil chemotaxis and respiratory burst by luteolin involves the blockade of MEK-, ERK-, and Akt-related signaling cascades.",,"['Lee, Jen-pei', 'Li, Yi-ching', 'Chen, Hung-yi', 'Lin, Ruey-hseng', 'Huang, Shiang-suo', 'Chen, Hui-ling', 'Kuan, Pai-chuan', 'Liao, Mao-fang', 'Chen, Chun-jung', 'Kuan, Yu-hsiang']",,,,
,PMC,Rapid detection of reassortment of pandemic H1N1/2009 influenza virus,http://dx.doi.org/10.1373/clinchem.2010.149179,PMC2956410,,,"BACKGROUND: Influenza viruses can generate novel reassortants in co-infected cells. The global circulation and occasional introductions of pandemic H1N1/2009 virus in humans and in pigs, respectively, might provide opportunities for this virus to reassort with other influenza viruses. These possible reassortment events might alter virulence and/or transmissibility of the new reassortants. Investigations that can detect such possible reassortants should therefore be included as a part of pandemic influenza surveillance plans. METHODS: We established a real-time RT-PCR-based strategy for the detection of reassortment of pandemic H1N1/2009 virus. Singleplex SYBR green-based RT-PCR assays specific for each gene segment of pandemic H1N1/2009 were developed. These assays were evaluated by influenza viruses with different genetic backgrounds. RESULTS: All human pandemic H1N1 (N=27) and all seasonal human (N=58) isolates were positive and negative, respectively, for all 8 segments. Of 48 swine influenza viruses isolated from our on-going surveillance program of influenza viruses in swine, 10 were positive in all reactions. All 8 viral segments of these 10 samples were confirmed to be of pandemic H1N1 origin, indicating that these were caused by zoonotic transmissions from human to pigs. The 38 swine viruses that are non-pandemic H1N1/2009 had 1 to 6 gene segments positive in the tests. Further characterization of these non-pandemic H1N1/2009 swine viruses indicated that these PCR positive genes are the precursor genes of pandemic H1N1/2009 virus. CONCLUSIONS: Our results demonstrated that these assays can detect re-introductions of pandemic H1N1/2009 virus in pigs. These assays might be useful screening tools for identifying viral reassortants derived from pandemic H1N1/2009 or its precursors.",,"['Poon, LLM', 'Mak, PWY', 'Li, OTW', 'Chan, KH', 'Cheung, CL', 'Ma, ES', 'Yen, HL', 'Vijaykrishna, D', 'Guan, Y', 'Peiris, JSM']",,,,
,PMC,Subgenomic messenger RNA amplification in coronaviruses,http://dx.doi.org/10.1073/pnas.1000378107,PMC2901459,,,"Coronaviruses possess the largest known RNA genome, a 27- to 32-kb (+)-strand molecule that replicates in the cytoplasm. During virus replication, a 3′ coterminal nested set of five to eight subgenomic (sg) mRNAs are made that are also 5′ coterminal with the genome, because they carry the genomic leader as the result of discontinuous transcription at intergenic donor signals during (−)-strand synthesis when templates for sgmRNA synthesis are made. An unanswered question is whether the sgmRNAs, which appear rapidly and abundantly, undergo posttranscriptional amplification. Here, using RT-PCR and sequence analyses of head-to-tail–ligated (−) strands, we show that after transfection of an in vitro–generated marked sgmRNA into virus-infected cells, the sgmRNA, like the genome, can function as a template for (−)-strand synthesis. Furthermore, when the transfected sgmRNA contains an internally placed RNA-dependent RNA polymerase template-switching donor signal, discontinuous transcription occurs at this site, and a shorter, 3′ terminally nested leader-containing sgmRNA is made, as evidenced by its leader–body junction and by the expression of a GFP gene. Thus, in principle, the longer-nested sgmRNAs in a natural infection, all of which contain potential internal template-switching donor signals, can function to increase the number of the shorter 3′-nested sgmRNAs. One predicted advantage of this behavior for coronavirus survivability is an increased chance of maintaining genome fitness in the 3′ one-third of the genome via a homologous recombination between the (now independently abundant) WT sgmRNA and a defective genome.",,"['Wu, Hung-Yi', 'Brian, David A.']",,,,
,PMC,Viral hijacking of the host ubiquitin system to evade interferon responses,http://dx.doi.org/10.1016/j.mib.2010.05.012,PMC2939720,,,"The post-translational attachment of ubiquitin or ubiquitin-like modifiers (ULMs) to proteins regulates many cellular processes including the generation of innate and adaptive immune responses to pathogens. Vice versa, pathogens counteract immune defense by inhibiting or redirecting the ubiquitination machinery of the host. A common immune evasion strategy is for viruses to target host immunoproteins for proteasomal or lysosomal degradation by employing viral or host ubiquitin ligases. By degrading key host adaptor and signaling molecules, viruses thus disable multiple immune response pathways including the production of and response to interferons as well as other innate host defense mechanisms. Recent work further revealed that viruses inhibit the ligation of ubiquitin or ULMs or remove ubiquitin from host cell proteins. Thus, viruses succeed in either stabilizing negative regulators of innate immune signaling or thwart host cell proteins that are activated by ubiquitin or ULM-modification.",,"['Viswanathan, Kasinath', 'Früh, Klaus', 'DeFilippis, Victor']",,,,
,PMC,"Epidemiology and Clinical Presentations of the Four Human Coronaviruses 229E, HKU1, NL63, and OC43 Detected over 3 Years Using a Novel Multiplex Real-Time PCR Method",http://dx.doi.org/10.1128/JCM.00636-10,PMC2916580,,,"Four human coronaviruses (HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43) are associated with a range of respiratory outcomes, including bronchiolitis and pneumonia. Their epidemiologies and clinical characteristics are poorly described and are often reliant on case reports. To address these problems, we conducted a large-scale comprehensive screening for all four coronaviruses by analysis of 11,661 diagnostic respiratory samples collected in Edinburgh, United Kingdom, over 3 years between July 2006 and June 2009 using a novel four-way multiplex real-time reverse transcription-PCR (RT-PCR) assay. Coronaviruses were detected in 0.3 to 0.85% of samples in all age groups. Generally, coronaviruses displayed marked winter seasonality between the months of December and April and were not detected in summer months, which is comparable to the pattern seen with influenza viruses. HCoV-229E was the exception; detection was confined to the winter of 2008 and was sporadic in the following year. There were additional longer-term differences in detection frequencies between seasons, with HCoV-OC43 predominant in the first and third seasons and HCoV-HKU1 dominating in the second (see Results for definitions of seasons). A total of 11 to 41% of coronaviruses detected were in samples testing positive for other respiratory viruses, although clinical presentations of coronavirus monoinfections were comparable to those of viruses which have an established role in respiratory disease, such as respiratory syncytial virus, influenza virus, and parainfluenza viruses. The novel multiplex assay for real-time pan-coronavirus detection enhances respiratory virus diagnosis, overcomes potential diagnostic problems arising through seasonal variation in coronavirus frequency, and provides novel insights into the epidemiology and clinical implications of coronaviruses.",,"['Gaunt, E. R.', 'Hardie, A.', 'Claas, E. C. J.', 'Simmonds, P.', 'Templeton, K. E.']",,,,
,PMC,T cell Epitope Specificity and Pathogenesis of MHV-1 Induced Disease in Susceptible and Resistant Hosts(1),http://dx.doi.org/10.4049/jimmunol.0902749,PMC2897948,,,"Intranasal MHV-1 infection of susceptible mouse strains mimics some important pathologic features observed in the lungs of SARS-CoV infected humans. The pathogenesis of Severe Acute Respiratory Syndrome (SARS) remains poorly understood, although increasing evidence suggests that immunopathology could play an important role. We previously reported that the adaptive immune response plays an important protective role in MHV-1 infected resistant B6 mice and that both CD4 and CD8 T-cells play a significant role in the development of morbidity and lung pathology following intranasal MHV-infection of susceptible C3H/HeJ and A/J mice. In this study we identified novel CD4 and CD8 epitopes in MHV-1 infected susceptible and resistant strains of mice. Susceptible C3H/HeJ mice mount robust and broad MHV-1 specific CD4 T-cell responses while in resistant B6 mice, antigen-specific CD8 T-cell responses dominate. We also show that previously immunized susceptible C3H/HeJ mice do not develop any morbidity and are completely protected following a lethal dose MHV-1 challenge despite mounting only a modest secondary T-cell response. Finally we demonstrate that the resistance displayed by B6 mice is not solely accounted for by the elaboration of a broad and vigorous MHV-1-specific CD8 T-cell response as MHV-1 infection of C3.SW-H2(b)/SnJ mice, which mount an equally robust CD8 T-cell response of the same specificity, is still associated with significant morbidity. Thus, identification of novel CD4 and CD8 T-cell epitopes for MHV-1 permitted high resolution analyses of pulmonary T-cell responses in a mouse model of SARS.",,"['Khanolkar, Aaruni', 'Fulton, Ross B.', 'Epping, Lecia L.', 'Pham, Nhat-Long', 'Tifrea, Dilea', 'Varga, Steven M.', 'Harty, John T.']",,,,
,PMC,Tick-Borne Encephalitis Virus Delays Interferon Induction and Hides Its Double-Stranded RNA in Intracellular Membrane Vesicles,http://dx.doi.org/10.1128/JVI.00176-10,PMC2919015,,,"Tick-borne encephalitis virus (TBEV) (family Flaviviridae, genus Flavivirus) accounts for approximately 10,000 annual cases of severe encephalitis in Europe and Asia. Here, we investigated the induction of the antiviral type I interferons (IFNs) (alpha/beta IFN [IFN-α/β]) by TBEV. Using strains Neudörfl, Hypr, and Absettarov, we demonstrate that levels of IFN-β transcripts and viral RNA are strictly correlated. Moreover, IFN induction by TBEV was dependent on the transcription factor IFN regulatory factor 3 (IRF-3). However, even strain Hypr, which displayed the strongest IFN-inducing activity and the highest RNA levels, substantially delayed the activation of IRF-3. As a consequence, TBEV can keep the level of IFN transcripts below the threshold value that would permit the release of IFN by the cell. Only after 24 h of infection have cells accumulated sufficient IFN transcripts to produce detectable amounts of secreted IFNs. The delay in IFN induction appears not to be caused by a specific viral protein, since the individual expressions of TBEV C, E, NS2A, NS2B, NS3, NS4A, NS4B, NS5, and NS2B-NS3, as well as TBEV infection itself, had no apparent influence on specific IFN-β induction. We noted, however, that viral double-stranded RNA (dsRNA), an important trigger of the IFN response, is immunodetectable only inside intracellular membrane compartments. Nonetheless, the dependency of IFN induction on IFN promoter stimulator 1 (IPS-1) as well as the phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2α) suggest the cytoplasmic exposure of some viral dsRNA late in infection. Using ultrathin-section electron microscopy, we demonstrate that, similar to other flaviviruses, TBEV rearranges intracellular membranes. Virus particles and membrane-connected vesicles (which most likely represent sites of virus RNA synthesis) were observed inside the endoplasmic reticulum. Thus, apparently, TBEV rearranges internal cell membranes to provide a compartment for its dsRNA, which is largely inaccessible for detection by cytoplasmic pathogen receptors. This delays the onset of IFN induction sufficiently to give progeny particle production a head start of approximately 24 h.",,"['Överby, Anna K.', 'Popov, Vsevolod L.', 'Niedrig, Matthias', 'Weber, Friedemann']",,,,
,PMC,The Cutting Edge: Membrane Anchored Serine Protease Activities in the Pericellular Microenvironment,http://dx.doi.org/10.1042/BJ20100046,PMC3680374,,,"The serine proteases of the trypsin-like (S1) family play critical roles in many key biological processes including digestion, blood coagulation, and immunity. Recent studies have identified members of this family which contain amino- or carboxy-terminal domains that serve to tether the serine protease catalytic domain directly at the plasma membrane. These membrane anchored serine proteases are proving to be key components of the cell machinery for activation of precursor molecules in the pericellular microenvironment, playing vital functions in the maintenance of homeostasis. Substrates activated by membrane anchored serine proteases include peptide hormones, growth and differentiation factors, receptors, enzymes, adhesion molecules and viral coat proteins. In addition, new insights into our understanding of the physiological functions of these proteases and their involvement in human pathology have come from animal models and patient studies. This review discusses emerging evidence for the diversity of this fascinating group of membrane serine proteases as potent modifiers of the pericellular microenvironment through proteolytic processing of diverse substrates. We also discuss the functional consequences of the activities of these proteases on mammalian physiology and disease.",,"['Antalis, Toni M.', 'Buzza, Marguerite S.', 'Hodge, Kathryn M.', 'Hooper, John D.', 'Netzel-Arnett, Sarah']",,,,
,PMC,The Origin and Prevention of Pandemics,http://dx.doi.org/10.1086/652860,PMC2874076,,,"Despite the fact that most emerging diseases stem from the transmission of pathogenic agents from animals to humans, the factors that mediate this process are still ill defined. What is known, however, is that the interface between humans and animals is of paramount importance in the process. This review will discuss the importance of the human-animal interface to the disease emergence process. We also provide an overview of factors that are believed to contribute to the origin and global spread of emerging infectious diseases and offer suggestions that may serve as future prevention strategies, such as social mobilization, public health education, behavioral change and communication strategies. Since there exists no comprehensive global surveillance system to monitor zoonotic disease emergence, the intervention measures discussed herein may prove effective temporary alternatives.",,"['Pike, Brian L.', 'Saylors, Karen E.', 'Fair, Joseph N.', 'LeBreton, Matthew', 'Tamoufe, Ubald', 'Djoko, Cyrille F.', 'Rimoin, Anne W.', 'Wolfe, Nathan D.']",,,,
,PMC,Population-Based Incidence of Human Metapneumovirus in Hospitalized Children,http://dx.doi.org/10.1086/652782,PMC2873123,,,"BACKGROUND: Human metapneumovirus (HMPV) is a leading cause of acute respiratory illness (ARI) in children. Population-based incidence rates and comprehensive clinical characterizations of disease have not been established. METHODS: We conducted population-based prospective surveillance for HMPV in two U.S. counties among children <5 years hospitalized with ARI or fever for two years. Nasal/throat swabs were tested for HMPV by real-time RT-PCR and genotyped. RESULTS: Forty-two of 1104 (3.8%) children tested positive for HMPV. The overall annual rate of HMPV-associated hospitalizations per 1000 children <5 years was 1.2 (95%CI 0.9–1.6). This rate was highest in infants 0–5 months (4.9/1000 [95%CI 2.9–7.2]), followed by children 6–11 months (2.9/1000 [95%CI 1.4–4.7]). The annual rate of HMPV-associated hospitalizations was less than respiratory syncytial virus, but similar to influenza and parainfluenzavirus (PIV) 3 in all age groups. The mean age of children hospitalized with HMPV was 6 months. Bronchiolitis, pneumonia and asthma were the most common diagnoses in children with HMPV. All four HMPV subgroups were detected during both years at both sites. HPMV was most prominent from March through May. CONCLUSIONS: HMPV was detected in 3.8% of children hospitalized with ARI or fever, with a population incidence similar to that of influenza and PIV3.",,"['Williams, John V.', 'Edwards, Kathryn M.', 'Weinberg, Geoffrey A.', 'Griffin, Marie R.', 'Hall, Caroline B.', 'Zhu, Yuwei', 'Szilagyi, Peter G.', 'Wang, Chiaoyin K.', 'Yang, Chin-Fen', 'Silva, David', 'Ye, Dan', 'Spaete, Richard R.', 'Crowe, James E.']",,,,
,PMC,WJG sets an example of internationalization for other Chinese academic journals,http://dx.doi.org/10.3748/wjg.v16.i22.2707,PMC2883125,,,"Supported by the “Special Fund for Key Academic Journals” of the National Natural Science Foundation of China, World Journal of Gastroenterology (WJG) has become a high-impact international clinical medical journal due to the great efforts of Professor Lian-Sheng Ma, Editor-in-Chief, and his team over several years. Now, WJG has successfully achieved a high degree of internationalization and sets a good example for other Chinese academic journals.",,"Zu, Guang-An",,,,
,PMC,The ISG15 conjugation system broadly targets newly synthesized proteins: implications for the anti-viral function of ISG15,http://dx.doi.org/10.1016/j.molcel.2010.05.002,PMC2887317,,,"ISG15 is an interferon-induced and anti-viral ubiquitin-like protein (Ubl). Herc5, the major E3 enzyme for ISG15, mediates the ISGylation of over 300 proteins in interferon-stimulated cells. In addressing this broad substrate selectivity of Herc5, we found that: 1) the range of substrates extends even further and includes many exogenously expressed foreign proteins, 2) ISG15 conjugation is restricted to newly synthesized pools of proteins, and 3) Herc5 is physically associated with polyribosomes. These results lead to a model for ISGylation in which Herc5 broadly modifies newly synthesized proteins in a co-translational manner. This represents a novel mechanism for conjugation of a Ubl and further suggests that, in the context of an interferon-stimulated cell, newly translated viral proteins may be primary targets of ISG15. Consistent with this, we demonstrate that ISGylation of human papillomavirus (HPV) L1 capsid protein has a dominant-inhibitory effect on the infectivity of HPV16 pseudoviruses.",,"['Durfee, Larissa A.', 'Lyon, Nancy', 'Seo, Kyungwoon', 'Huibregtse, Jon M.']",,,,
,PMC,The SCHOOL of nature: III. From mechanistic understanding to novel therapies,http://dx.doi.org/10.4161/self.1.3.12794,PMC3047783,,,"Protein-protein interactions play a central role in biological processes and thus represent an appealing target for innovative drug design and development. They can be targeted by small molecule inhibitors, modulatory peptides and peptidomimetics, which represent a superior alternative to protein therapeutics that carry many disadvantages. Considering that transmembrane signal transduction is an attractive process to therapeutically control multiple diseases, it is fundamentally and clinically important to mechanistically understand how signal transduction occurs. Uncovering specific protein-protein interactions critical for signal transduction, a general platform for receptor-mediated signaling, the signaling chain homooligomerization (SCHOOL) platform, suggests these interactions as universal therapeutic targets. Within the platform, the general principles of signaling are similar for a variety of functionally unrelated receptors. This suggests that global therapeutic strategies targeting key protein-protein interactions involved in receptor triggering and transmembrane signal transduction may be used to treat a diverse set of diseases. This also assumes that clinical knowledge and therapeutic strategies can be transferred between seemingly disparate disorders, such as T cell-mediated skin diseases and platelet disorders or combined to develop novel pharmacological approaches. Intriguingly, human viruses use the SCHOOL-like strategies to modulate and/or escape the host immune response. These viral mechanisms are highly optimized over the millennia, and the lessons learned from viral pathogenesis can be used practically for rational drug design. Proof of the SCHOOL concept in the development of novel therapies for atopic dermatitis, rheumatoid arthritis, cancer, platelet disorders and other multiple indications with unmet needs opens new horizons in therapeutics.",,"Sigalov, Alexander B",,,,
,PMC,Viral tricks to grid-lock the type I interferon system,http://dx.doi.org/10.1016/j.mib.2010.05.009,PMC2920345,,,"Type I interferons (IFN) play a critical role in the innate immune avant-garde against viral infections. Virtually all viruses have developed means to counteract the induction, signaling or antiviral actions of the IFN circuit. Over 170 different virus-encoded IFN-antagonists from 93 distinct viruses have been described up to now, indicating that most viruses interfere with multiple stages of the IFN response. Although every viral IFN antagonist is unique in its own right, four main mechanisms are employed to circumvent innate immune responses: i) general inhibition of cellular gene expression, and ii) sequestration, iii) proteolytic cleavage or iv) proteasomal degradation of key components of the IFN system. The increasing understanding of how different viral IFN antagonists function has been translated to the generation of viruses with mutant IFN antagonists as potential live vaccine candidates. Moreover, IFN antagonists are attractive targets for inhibition by small-molecule compounds.",,"['Versteeg, Gijs A.', 'García-Sastre, Adolfo']",,,,
,PMC,Differential Sensitivity of Well-Differentiated Avian Respiratory Epithelial Cells to Infection by Different Strains of Infectious Bronchitis Virus,http://dx.doi.org/10.1128/JVI.00463-10,PMC2919026,,,"Infectious bronchitis virus (IBV) is an avian coronavirus affecting the respiratory tract of chickens. To analyze IBV infection of the lower respiratory tract, we applied a technique that uses precision-cut lung slices (PCLSs). This method allows infection of bronchial cells within their natural tissue composition under in vitro conditions. We demonstrate that IBV strains 4/91, Italy02, and QX infect ciliated and mucus-producing cells of the bronchial epithelium, whereas cells of the parabronchial tissue are resistant to infection. This is the first study, using PCLSs of chicken origin, to analyze virus infection. PCLSs should also be a valuable tool for investigation of other respiratory pathogens, such as avian influenza viruses.",,"['Abd El Rahman, Sahar', 'Winter, Christine', 'El-Kenawy, Ali', 'Neumann, Ulrich', 'Herrler, Georg']",,,,
,PMC,Attachment of Mouse Hepatitis Virus to O-Acetylated Sialic Acid Is Mediated by Hemagglutinin-Esterase and Not by the Spike Protein,http://dx.doi.org/10.1128/JVI.00566-10,PMC2919023,,,"The members of Betacoronavirus phylocluster A possess two types of surface projections, one comprised of the spike protein (S) and the other of hemagglutinin-esterase (HE). Purportedly, these viruses bind to O-acetylated sialic acids (O-Ac-Sias) primarily through S, with HE serving merely as receptor-destroying enzyme. Here, we show that, in apparent contrast to human and ungulate host range variants of Betacoronavirus-1, murine coronaviruses actually bind to O-Ac-Sias via HE exclusively. Apparently, expansion of group A betacoronaviruses into new hosts and niches was accompanied by changes in HE ligand and substrate preference and in the roles of HE and S in Sia receptor usage.",,"['Langereis, Martijn A.', 'van Vliet, Arno L. W.', 'Boot, Willemijn', 'de Groot, Raoul J.']",,,,
,PMC,"TYPE I INTERFERON SIGNALS CONTROL THEILER’S VIRUS INFECTION SITE, CELLULAR INFILTRATION AND T CELL STIMULATION IN THE CNS",http://dx.doi.org/10.1016/j.jneuroim.2010.05.028,PMC2937062,,,"Theiler’s murine encephalomyelitis virus (TMEV) establishes a persistent infection in the central nervous system (CNS). To examine the role of type I interferon (IFN-I)-mediated signals in TMEV infection, mice lacking a subunit of the type I IFN receptor (IFN-IR KO mice) were utilized. In contrast to wildtype mice, IFN-IR KO mice developed rapid fatal encephalitis accompanied with greater viral load and infiltration of immune cells to the CNS. The proportion of virus-specific CD4(+) and CD8(+) T cell responses in the CNS was significantly lower in IFN-IR KO mice during the early stage of infection. Levels of IFN-γ and IL-17 produced by isolated primed CD4(+) T cells in response to DCs from TMEV-infected IFN-IRKO mice were also lower than those stimulated by DCs from TMEV-infected wildtype control mice. The less efficient stimulation of virus-specific T cells by virus-infected antigen presenting cells is attributable in part to the low level expression of activation markers on TMEV-infected cells from IFN-IR KO mice. However, due to high levels of cellular infiltration and viral loads in the CNS, the overall numbers of virus-specific T cells are higher in IFN-IR KO mice during the later stage of viral infection. These results suggest that IFN-I-mediated signals play important roles in controlling cellular infiltration to the CNS and shaping local T cell immune responses.",,"['Jin, Young-Hee', 'Hou, Wanqiu', 'Kim, Seung Jae', 'Fuller, Alyson C.', 'Kang, Bongsu', 'Goings, Gwen', 'Miller, Stephen D.', 'Kim, Byung S.']",,,,
,PMC,SHAPE-Directed RNA Secondary Structure Prediction,http://dx.doi.org/10.1016/j.ymeth.2010.06.007,PMC2941709,,,"The diverse functional roles of RNA are determined by its underlying structure. Accurate and comprehensive knowledge of RNA structure would inform a broader understanding of RNA biology and facilitate exploiting RNA as a biotechnological tool and therapeutic target. Determining the pattern of base pairing, or secondary structure, of RNA is a first step in these endeavors. Advances in experimental, computational, and comparative analysis approaches for analyzing secondary structure have yielded accurate structures for many small RNAs, but only a few large (>500 nts) RNAs. In addition, most current methods for determining a secondary structure require considerable effort, analytical expertise, and technical ingenuity. In this review, we outline an efficient strategy for developing accurate secondary structure models for RNAs of arbitrary length. This approach melds structural information obtained using SHAPE chemistry with structure prediction using nearest-neighbor rules and the dynamic programming algorithm implemented in the RNAstructure program. Prediction accuracies reach ≥95% for RNAs on the kilobase scale. This approach facilitates both development of new models and refinement of existing RNA structure models, which we illustrate using the Gag-Pol frameshift element in an HIV-1 M-group genome. Most promisingly, integrated experimental and computational refinement brings closer the ultimate goal of efficiently and accurately establishing the secondary structure for any RNA sequence.",,"['Low, Justin T.', 'Weeks, Kevin M.']",,,,
,PMC,Respiratory Syncytial Virus Limits α Subunit of Eukaryotic Translation Initiation Factor 2 (eIF2α) Phosphorylation to Maintain Translation and Viral Replication,http://dx.doi.org/10.1074/jbc.M109.077321,PMC2911276,,,"The impact of respiratory syncytial virus (RSV) on morbidity and mortality is significant in that it causes bronchiolitis in infants, exacerbations in patients with obstructive lung disease, and pneumonia in immunocompromised hosts. RSV activates protein kinase R (PKR), a cellular kinase relevant to limiting viral replication (Groskreutz, D. J., Monick, M. M., Powers, L. S., Yarovinsky, T. O., Look, D. C., and Hunninghake, G. W. (2006) J. Immunol. 176, 1733–1740). It is activated by autophosphorylation, likely triggered by a double-stranded RNA intermediate during replication of the virus. In most instances, ph-PKR targets the α subunit of eukaryotic translation initiation factor 2 (eIF2α) protein via phosphorylation, leading to an inhibition of translation of cellular and viral protein. However, we found that although ph-PKR increases in RSV infection, significant eIF2α phosphorylation is not observed, and inhibition of protein translation does not occur. RSV infection attenuates eIF2α phosphorylation by favoring phosphatase rather than kinase activity. Although PKR is activated, RSV sequesters PKR away from eIF2α by binding of the kinase to the RSV N protein. This occurs in conjunction with an increase in the association of the phosphatase, PP2A, with eIF2α following PKR activation. The result is limited phosphorylation of eIF2α and continued translation of cellular and viral proteins.",,"['Groskreutz, Dayna J.', 'Babor, Ellen C.', 'Monick, Martha M.', 'Varga, Steven M.', 'Hunninghake, Gary W.']",,,,
,PMC,Cell replacement therapies to promote remyelination in a viral model of demyelination,http://dx.doi.org/10.1016/j.jneuroim.2010.05.013,PMC2919340,,,"Persistent infection of the central nervous system (CNS) of mice with the neuroadapted JHM strain of mouse hepatitis (MHV) is characterized by ongoing demyelination mediated by inflammatory T cells and macrophages that is similar both clinically and histologically with the human demyelinating disease multiple sclerosis (MS). Although extensive demyelination occurs in mice persistently-infected with MHV there is only limited remyelination. Therefore, the MHV model of demyelination is a relevant model for studying disease and evaluating therapeutic approaches to protect cells of the oligodendrocyte lineage and promote remyelination. This concept is further highlighted as the etiology of MS remains enigmatic, but viruses have long been considered as potential triggering agents in initiating and/or maintaining MS symptoms. As such, understanding mechanisms associated with promoting repair within the CNS in the context of a persistent viral infection is critical given the possible viral eitiology of MS. This review focuses on recent studies using either mouse neural stem cells (NSCs) or human oligodendrocyte progenitor cells (OPCs) derived from human embryonic stem cell (hESCs) to promote remyelination in mice persistently infected with MHV. In addition, the potential role for chemokines in positional migration of transplanted cells is addressed.",,"['Tirotta, Emanuele', 'Carbajal, Kevin S.', 'Schaumburg, Chris S.', 'Whitman, Lucia', 'Lane, Thomas E.']",,,,
,PMC,An Antibody against a Novel and Conserved Epitope in the Hemagglutinin 1 Subunit Neutralizes Numerous H5N1 Influenza Viruses,http://dx.doi.org/10.1128/JVI.02593-09,PMC2916527,,,"The spread of the recently emerged, highly pathogenic H5N1 avian influenza virus has raised concern. Preclinical studies suggest that passive immunotherapy could be a new form of treatment for H5N1 virus infection. Here, a neutralizing monoclonal antibody (MAb) against the hemagglutinin (HA) of the influenza A/chicken/Hatay/2004 H5N1 virus, MAb 9F4, was generated and characterized. MAb 9F4 binds both the denatured and native forms of HA. It was shown to recognize the HA proteins of three heterologous strains of H5N1 viruses belonging to clades 1, 2.1, and 2.2, respectively. By use of lentiviral pseudotyped particles carrying HA on the surface, MAb 9F4 was shown to effectively neutralize the homologous strain, Hatay04, and another clade 1 strain, VN04, at a neutralization titer of 8 ng/ml. Furthermore, MAb 9F4 also neutralized two clade 2 viruses at a neutralizing titer of 40 ng/ml. The broad cross-neutralizing activity of MAb 9F4 was confirmed by its ability to neutralize live H5N1 viruses of clade 2.2.2. Epitope-mapping analysis revealed that MAb 9F4 binds a previously uncharacterized epitope below the globular head of the HA1 subunit. Consistently, this epitope is well conserved among the different clades of H5N1 viruses. MAb 9F4 does not block the interaction between HA and its receptor but prevents the pH-mediated conformational change of HA. MAb 9F4 was also found to be protective, both prophylactically and therapeutically, against a lethal viral challenge of mice. Taken together, our results showed that MAb 9F4 is a neutralizing MAb that binds a novel and well-conserved epitope in the HA1 subunit of H5N1 viruses.",,"['Oh, Hsueh-Ling Janice', 'Åkerström, Sara', 'Shen, Shuo', 'Bereczky, Sándor', 'Karlberg, Helen', 'Klingström, Jonas', 'Lal, Sunil K.', 'Mirazimi, Ali', 'Tan, Yee-Joo']",,,,
,PMC,Accessory Protein 5a Is a Major Antagonist of the Antiviral Action of Interferon against Murine Coronavirus,http://dx.doi.org/10.1128/JVI.00385-10,PMC2916514,,,"The type I interferon (IFN) response plays an essential role in the control of in vivo infection by the coronavirus mouse hepatitis virus (MHV). However, in vitro, most strains of MHV are largely resistant to the action of this cytokine, suggesting that MHV encodes one or more functions that antagonize or evade the IFN system. A particular strain of MHV, MHV-S, exhibited orders-of-magnitude higher sensitivity to IFN than prototype strain MHV-A59. Through construction of interstrain chimeric recombinants, the basis for the enhanced IFN sensitivity of MHV-S was found to map entirely to the region downstream of the spike gene, at the 3′ end of the genome. Sequence analysis revealed that the major difference between the two strains in this region is the absence of gene 5a from MHV-S. Creation of a gene 5a knockout mutant of MHV-A59 demonstrated that a major component of IFN resistance maps to gene 5a. Conversely, insertion of gene 5a, or its homologs from related group 2 coronaviruses, at an upstream genomic position in an MHV-A59/S chimera restored IFN resistance. This is the first demonstration of a coronavirus gene product that can protect that same virus from the antiviral state induced by IFN. Neither protein kinase R, which phosphorylates eukaryotic initiation factor 2, nor oligoadenylate synthetase, which activates RNase L, was differentially activated in IFN-treated cells infected with MHV-A59 or MHV-S. Thus, the major IFN-induced antiviral activities that are specifically inhibited by MHV, and possibly by other coronaviruses, remain to be identified.",,"['Koetzner, Cheri A.', 'Kuo, Lili', 'Goebel, Scott J.', 'Dean, Amy B.', 'Parker, Monica M.', 'Masters, Paul S.']",,,,
,PMC,"The “Contaminating Agent” UNRRA, Displaced Persons, and Venereal Disease in Germany, 1945–1947",http://dx.doi.org/10.2105/AJPH.2008.153098,PMC2866594,,,"World War II created a large group of persecuted, homeless or stateless people who came to be united under the term “displaced persons” (DPs). The United Nations Relief and Rehabilitation Administration (UNRRA) was charged with the care of these individuals in various camps in Germany, although the military governments of the respective zones of occupation had ultimate authority over them. Among the various public health efforts directed toward DPs was a campaign against venereal disease during which compulsory examinations were particularly stressed by the military governments. The controversy resulting from this campaign opens a new window on the complex context of an international organization working under the roof of a national authority to achieve common—or differing—public health goals.",,"Haushofer, Lisa",,,,
,PMC,Geographical information systems and tropical medicine,http://dx.doi.org/10.1179/136485910X12743554759867,PMC3727654,,,"In terms of their applicability to the field of tropical medicine, geographical information systems (GIS) have developed enormously in the last two decades. This article reviews some of the pertinent and representative applications of GIS, including the use of such systems and remote sensing for the mapping of Chagas disease and human helminthiases, the use of GIS in vaccine trials, and the global applications of GIS for health-information management, disease epidemiology, and pandemic planning. The future use of GIS as a decision-making tool and some barriers to the widespread implementation of such systems in developing settings are also discussed.",,"['KHAN, O. A.', 'DAVENHALL, W.', 'ALI, M.', 'CASTILLO-SALGADO, C.', 'VAZQUEZ-PROKOPEC, G.', 'KITRON, U.', 'SOARES MAGALHÃES, R. J.', 'CLEMENTS, A. C. A.']",,,,
,PMC,Destruction of Microbial Collections in Response to Select Agent and Toxin List Regulations,http://dx.doi.org/10.1089/bsp.2010.0012,PMC2982716,,,"In this study we have followed up on anecdotal and hearsay evidence that microbial collections were destroyed in the United States following the imposition of the regulations associated with the Select Agents and Toxins List, to validate or refute that information. Using a questionnaire, we documented 13 episodes of microbial collection destruction involving viral, bacterial, and fungal strains, which we believe is almost certainly an underestimate of the number of collections destroyed. In every case, the motivation for the destruction of the collection was a desire to avoid the perceived burdens of the regulatory environment associated with operating under the Select Agent Regulations. Some institutions that destroyed isolates considered, and in some cases tried, transferring their collections to registered institutions prior to collection destruction but desisted when confronted with transport regulations. Destruction of microbial collections represents a loss of strains and biological diversity available for biomedical research and future mechanistic, forensic, and epidemiologic investigations. Given the rapid evolution of microbial strains, the destruction of archival collections is a potentially irretrievable loss that was an unintended consequence of regulations to protect society against the nefarious use of biological agents. Furthermore, unregistered institutions continue to destroy newly acquired clinical isolates, thus preventing the establishment of new repository collections. We recommend that government agencies develop plans to ensure that microbial collections are preserved when considering future additions to microbial threat lists under which the possession of certain microbes is criminalized.",,"['Casadevall, Arturo', 'Imperiale, Michael J.']",,,,
,PMC,Cyclophilin–CD147 interactions: a new target for anti-inflammatory therapeutics,http://dx.doi.org/10.1111/j.1365-2249.2010.04115.x,PMC2883100,,,"CD147 is a widely expressed plasma membrane protein that has been implicated in a variety of physiological and pathological activities. It is best known for its ability to function as extracellular matrix metalloproteinase inducer (hence the other name for this protein, EMMPRIN), but has also been shown to regulate lymphocyte responsiveness, monocarboxylate transporter expression and spermatogenesis. These functions reflect multiple interacting partners of CD147. Among these CD147-interacting proteins cyclophilins represent a particularly interesting class, both in terms of structural considerations and potential medical implications. CD147 has been shown to function as a signalling receptor for extracellular cyclophilins A and B and to mediate chemotactic activity of cyclophilins towards a variety of immune cells. Recent studies using in vitro and in vivo models have demonstrated a role for cyclophilin–CD147 interactions in the regulation of inflammatory responses in a number of diseases, including acute lung inflammation, rheumatoid arthritis and cardiovascular disease. Agents targeting either CD147 or cyclophilin activity showed significant anti-inflammatory effects in experimental models, suggesting CD147–cyclophilin interactions may be a good target for new anti-inflammatory therapeutics. Here, we review the recent literature on different aspects of cyclophilin–CD147 interactions and their role in inflammatory diseases.",,"['Yurchenko, V', 'Constant, S', 'Eisenmesser, E', 'Bukrinsky, M']",,,,
,PMC,Mapping the Anatomy of Respiratory Syncytial Virus Infection of the Upper Airways in Chinchillas (Chinchilla lanigera),,PMC2890398,,,"Although most viral infections of the upper respiratory tract can predispose to bacterial otitis media, human respiratory syncytial virus (HRSV) is the predominant viral copathogen of this highly prevalent pediatric polymicrobial disease. Rigorous study of the specific mechanisms by which HRSV predisposes to otitis media has been hindered by lack of a relevant animal model. We recently reported that the chinchilla, the preferred rodent host for studying otitis media, is semipermissive for upper-airway HRSV infection. In the current study, we defined the anatomy and kinetics of HRSV infection and spread in the upper airway of chinchilla hosts. Chinchillas were challenged intranasally with a fluorescent-protein–expressing HRSV. Upper-airway tissues were recovered at multiple time points after viral challenge and examined by confocal microscopy and immunohistochemistry. HRSV replication was observed from the rostral- to caudalmost regions of the nasal cavity as well as throughout the Eustachian tube in a time-dependent manner. Although fluorescence was not observed and virus was not detected in nasopharyngeal lavage fluids 14 d after infection, the latest time point examined in this study, occasional clusters of immunopositive cells were present, suggesting that the nasal cavity may serve as a reservoir for HRSV. These data provide important new information concerning the time course of HRSV infection of the uppermost airway and suggest that chinchillas may be useful for modeling the HRSV-induced changes that predispose to secondary bacterial infection.",,"['Grieves, Jessica L', 'Jurcisek, Joseph A', 'Quist, Brian', 'Durbin, Russell K', 'Peeples, Mark E', 'Durbin, Joan E', 'Bakaletz, Lauren O']",,,,
,PMC,Angiotensin-Converting Enzyme 2: Central Regulator for Cardiovascular Function,http://dx.doi.org/10.1007/s11906-010-0105-7,PMC3093757,,,"Angiotensin-converting enzyme 2 (ACE2) is a new component of the renin-angiotensin system (RAS). Accumulating evidence shows that ACE2 provides protective effects in peripheral tissues and has great potential for the treatment of RAS-related diseases. The role of ACE2 in the central nervous system is not well established. However, in recent years, much more progress has been made on the studies of this carboxypeptidase in the central regulation of blood pressure and cardiovascular function in general. It has been shown that brain ACE2 interacts with the other components of the RAS (ACE, angiotensin II, and angiotensin II type 1 receptor), protects baroreflex and autonomic function, stimulates nitric oxide release, reduces oxidative stress, and prevents the development of or attenuates hypertension. These data support the critical role of ACE2 in the central regulation of cardiovascular function. This review summarizes recently published data on the central effects of ACE2 in the regulation of cardiovascular function.",,"['Xia, Huijing', 'Lazartigues, Eric']",,,,
,PMC,Localization and Targeting of an Unusual Pyridine Nucleotide Transhydrogenase in Entamoeba histolytica,http://dx.doi.org/10.1128/EC.00011-10,PMC2901640,,,"Pyridine nucleotide transhydrogenase (PNT) catalyzes the direct transfer of a hydride-ion equivalent between NAD(H) and NADP(H) in bacteria and the mitochondria of eukaryotes. PNT was previously postulated to be localized to the highly divergent mitochondrion-related organelle, the mitosome, in the anaerobic/microaerophilic protozoan parasite Entamoeba histolytica based on the potential mitochondrion-targeting signal. However, our previous proteomic study of isolated phagosomes suggested that PNT is localized to organelles other than mitosomes. An immunofluorescence assay using anti-E. histolytica PNT (EhPNT) antibody raised against the NADH-binding domain showed a distribution to the membrane of numerous vesicles/vacuoles, including lysosomes and phagosomes. The domain(s) required for the trafficking of PNT to vesicles/vacuoles was examined by using amoeba transformants expressing a series of carboxyl-terminally truncated PNTs fused with green fluorescent protein or a hemagglutinin tag. All truncated PNTs failed to reach vesicles/vacuoles and were retained in the endoplasmic reticulum. These data indicate that the putative targeting signal is not sufficient for the trafficking of PNT to the vesicular/vacuolar compartments and that full-length PNT is necessary for correct transport. PNT displayed a smear of >120 kDa on SDS-PAGE gels. PNGase F and tunicamycin treatment, chemical degradation of carbohydrates, and heat treatment of PNT suggested that the apparent aberrant mobility of PNT is likely attributable to its hydrophobic nature. PNT that is compartmentalized to the acidic compartments is unprecedented in eukaryotes and may possess a unique physiological role in E. histolytica.",,"['Yousuf, Mohammad Abu', 'Mi-ichi, Fumika', 'Nakada-Tsukui, Kumiko', 'Nozaki, Tomoyoshi']",,,,
,PMC,Antibody-profiling technologies for studying humoral responses to infectious agents,http://dx.doi.org/10.1586/erv.10.50,PMC3417761,,,"Analyses of humoral responses against different infectious agents are critical for infectious disease diagnostics, understanding pathogenic mechanisms, and the development and monitoring of vaccines. While ELISAs are often used to measure antibody responses to one or several targets, new antibody-profiling technologies, such as protein microarrays, can now evaluate antibody responses to hundreds, or even thousands, of recombinant antigens at one time. These large-scale studies have uncovered new antigenic targets, provided new insights into vaccine research and yielded an overview of immunoreactivity against almost the entire proteome of certain pathogens. However, solid-phase antigen arrays also have drawbacks that limit the type of information obtained, including suboptimal detection of conformational epitopes, high backgrounds due to impure antigens and a narrow dynamic range of detection. We have developed a solution-phase antibody-profiling technology, luciferase immunoprecipitation systems (LIPS), which harnesses light-emitting recombinant antigen fusion proteins to quantitatively measure patient antibody titers. Owing to the highly linear light output of the luciferase reporter, some antibodies can be detected without serum dilution in a dynamic range of detection often spanning seven orders of magnitude. When LIPS is applied iteratively with multiple target antigens, a high-definition antibody profile is obtained. Here, we discuss the application of these different antibody-profiling technologies and their associated limitations with particular emphasis on protein microarrays. We also describe LIPS in detail and discuss several clinically relevant uses of the technology. Together, these new technologies offer new tools for understanding humoral responses to known and emerging infectious agents.",,"['Burbelo, Peter D', 'Ching, Kathryn H', 'Bush, Emily R', 'Han, Brian L', 'Iadarola, Michael J']",,,,
,PMC,CX(3)CR1 and VAP-1 Dependent Recruitment of CD16(+) Monocytes Across Human Liver Sinusoidal Endothelium,http://dx.doi.org/10.1002/hep.23591,PMC2919204,,,"BACKGROUND: The liver contains macrophages and myeloid dendritic cells (mDC) that are critical for the regulation of hepatic inflammation. Most hepatic macrophages and mDC are derived from monocytes recruited from blood via poorly understood interactions with hepatic sinusoidal endothelial cells (HSEC). Human CD16(+) monocytes are believed to contain the precursor populations for tissue macrophages and mDC. RESULTS: We report that CD16(+) cells localize to areas of active inflammation and fibrosis in chronic inflammatory liver disease and that a unique combination of cell surface receptors promotes the transendothelial migration of CD16(+) monocytes through human HSEC under physiological flow. CX(3)CR1 activation was the dominant pertussis-sensitive mechanism controlling transendothelial migration under flow and expression of the CX(3)CR1 ligand CX(3)CL1 is increased on hepatic sinusoids in chronic inflammatory liver disease. Exposure of CD16(+) monocytes to immobilized purified CX(3)CL1 triggered β1 integrin-mediated adhesion to VCAM-1 and induced the development of a migratory phenotype. Following transmigration or exposure to soluble CX(3)CL1, CD16(+) monocytes rapidly but transiently lost expression of CX(3)CR1. Adhesion and transmigration across HSEC under flow was also dependent on vascular adhesion protein-1 (VAP-1) on the HSEC. CONCLUSIONS: Our data suggest that CD16(+) monocytes are recruited by a combination of adhesive signals involving VAP-1 and CX(3)CR1 mediated integrin-activation. Thus a novel combination of surface molecules, including VAP-1 and CX(3)CL1 promotes the recruitment of CD16(+) monocytes to the liver allowing them to localize at sites of chronic inflammation and fibrosis.",,"['Aspinall, Alexander I.', 'Curbishley, Stuart M.', 'Lalor, Patricia F.', 'Weston, Chris J.', 'Blahova, Miroslava', 'Liaskou, Evaggelia', 'Adams, Rebecca M', 'Holt, Andrew P.', 'Adams, David H.']",,,,
,PMC,Effect of mucosal and systemic immunization with virus-like particles of severe acute respiratory syndrome coronavirus in mice,http://dx.doi.org/10.1111/j.1365-2567.2010.03231.x,PMC2878469,,,"Nasal administration has emerged as a promising and attractive route for vaccination, especially for the prophylaxis of respiratory diseases. Our previous studies have shown that severe acute respiratory syndrome coronavirus (SARS-CoV) virus-like particles (VLPs) can be assembled using a recombinant baculovirus (rBV) expression system and such VLPs induce specific humoral and cellular immune responses in mice after subcutaneous injection. Here, we investigated mucosal immune responses to SARS-CoV VLPs in a mouse model. Mice were immunized in parallel, intraperitoneally or intranasally, with VLPs alone or with VLPs plus cytosine–phosphate–guanosine (CpG). Immune responses, including the production of SARS-CoV-specific serum immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA), were determined in mucosal secretions and tissues. Both immunizations induced SARS-CoV-specific IgG, although the levels of IgG in groups immunized via the intraperitoneal (i.p.) route were higher. sIgA was detected in saliva in groups immunized intranasally but not in groups immunized intraperitoneally. CpG had an adjuvant effect on IgA production in genital tract washes when administered intranasally but only affected IgA production in faeces samples when administered intraperitoneally. In addition, IgA was also detected in mucosal tissues from the lung and intestine, while CpG induced an increased level of IgA in the intestine. Most importantly, neutralization antibodies were detected in sera after i.p. and intranasal (i.n.) immunizations. Secretions in genital tract washes from the i.n. group also showed neutralization activity. Furthermore, VLPs that were administered intraperitoneally elicited cellular immune responses as demonstrated by enzyme-linked immunospot (ELISPOT) assay analyses. In summary, our study indicates that mucosal immunization with rBV SARS-CoV VLPs represent an effective means for eliciting protective systemic and mucosal immune responses against SARS-CoV, providing important information for vaccine design.",,"['Lu, Baojing', 'Huang, Yi', 'Huang, Li', 'Li, Bao', 'Zheng, Zhenhua', 'Chen, Ze', 'Chen, Jianjun', 'Hu, Qinxue', 'Wang, Hanzhong']",,,,
,PMC,Lentiviral Vectors for Immune Cells Targeting,http://dx.doi.org/10.3109/08923970903420582,PMC2864798,,,"Lentiviral vectors are efficient gene delivery vehicles suitable for delivering long-term transgene expression in various cell types. Engineering lentiviral vectors to have the capacity to transduce specific cell types is of great interest to advance the translation of lentiviral vectors towards the clinic. Here we provide an overview of innovative approaches to target lentiviral vectors to cells of the immune system. In this overview we distinguish between two types of lentiviral vector targeting strategies: 1) targeting of the vectors to specific cells by lentiviral vector surface modifications, and 2) targeting at the level of transgene transcription by insertion of tissue-specific promoters to drive transgene expression. It is clear that each strategy is of enormous value but ultimately combining these approaches may help reduce the effects of off-target expression and improve the efficiency and saftey of lentiviral vectors for gene therapy.",,"['Froelich, Steven', 'Tai, April', 'Wang, Pin']",,,,
,PMC,Human Rhinovirus Proteinase 2A Induces Th1 and Th2 Immunity in COPD,http://dx.doi.org/10.1016/j.jaci.2010.02.035,PMC2881843,,,"BACKGROUND: Tobacco related lung diseases including chronic obstructive pulmonary disease (COPD), are major causes of lung-related disability and death worldwide. Acute exacerbation of COPD (AE-COPD) is commonly associated with upper and lower respiratory viral infections and may result in respiratory failure in those with advanced lung disease. OBJECTIVE: We sought to determine the mechanism underlying COPD exacerbation, and host response to pathogen-derived factors. METHODS: Over a 24 months period, we assessed the viral causes for upper and lower respiratory infections in COPD (n=155) and control (n=103) subjects. We collected nasal and bronchoalveolar lavage (BAL) fluid and peripheral blood under baseline and exacerbated condition. We determined the effect of human rhinovirus (HRV) proteinases on T cell activation in humans, and in mice. RESULTS: HRVs are isolated from nasal and lung fluid from subjects with AE-COPD. BAL fluid, and CD4 T cells from COPD patients exhibited a type 1 T helper (Th1), and Th2 cell cytokine phenotype during acute infection. HRV-encoded proteinase 2A activated monocyte-derived dendritic cells in vitro, and induced strong Th1, and Th2 immune responses from CD4 T cells. Intranasal administration of recombinant rhinovirus proteinase 2A in mice resulted in an increase in airway hyperreactivity, lung inflammation, and IL-4 and IFN-γ production from CD4 T cells. CONCLUSION: Our findings suggest that patients with severe COPD show Th1 and Th2 bias responses during AE-COPD. HRV-encoded proteinase 2A, like other microbial proteinases, could provide a Th1 and Th2-biasing adjuvant factor during upper and lower respiratory infection in patients with severe COPD. Alteration of the immune response to secreted viral proteinases may contribute to worsening of dyspnea and respiratory failure in COPD.",,"['Singh, Manisha', 'Lee, Seung-Hyo', 'Porter, Paul', 'Xu, Chuang', 'Ohno, Ayako', 'Atmar, Robert L.', 'Greenberg, Stephen B.', 'Bandi, Venkata', 'Gern, Jim', 'Amineva, Svetlana', 'Aminev, Alex', 'Skern, Tim', 'Smithwick, Pamela', 'Perusich, Sarah', 'Barrow, Nadia', 'Roberts, Luz', 'Corry, David B.', 'Kheradmand, Farrah']",,,,
,PMC,Viral Respiratory Infections and Asthma: the Course Ahead,http://dx.doi.org/10.1016/j.jaci.2010.04.002,PMC2880817,,,"Inquiries into the relationships between viral respiratory illnesses and the inception and exacerbation of asthma are being facilitated by recent advances in research approaches and technology. In this article, we identify important knowledge gaps and future research questions, and we discuss how new investigational tools, including improved respiratory virus detection techniques, will permit current and future researchers to define these relationships and the host, virus, developmental, and environmental mechanisms that regulate them. A better understanding of these processes should facilitate the development of improved strategies for the prevention and treatment of virus-induced wheezing illnesses and asthma exacerbations and, possibly, the ultimate goal of discovering effective approaches for the primary prevention of asthma.",,"['Rosenthal, Louis A.', 'Avila, Pedro C.', 'Heymann, Peter W.', 'Martin, Richard J.', 'Miller, E. Kathryn', 'Papadopoulos, Nikolaos G.', 'Peebles, R. Stokes', 'Gern, James E.']",,,,
,PMC,A Novel L-ficolin/Mannose-binding Lectin Chimeric Molecule with Enhanced Activity against Ebola Virus,http://dx.doi.org/10.1074/jbc.M110.106260,PMC2915709,,,"Ebola viruses constitute a newly emerging public threat because they cause rapidly fatal hemorrhagic fevers for which no treatment exists, and they can be manipulated as bioweapons. We targeted conserved N-glycosylated carbohydrate ligands on viral envelope surfaces using novel immune therapies. Mannose-binding lectin (MBL) and L-ficolin (L-FCN) were selected because they function as opsonins and activate complement. Given that MBL has a complex quaternary structure unsuitable for large scale cost-effective production, we sought to develop a less complex chimeric fusion protein with similar ligand recognition and enhanced effector functions. We tested recombinant human MBL and three L-FCN/MBL variants that contained the MBL carbohydrate recognition domain and varying lengths of the L-FCN collagenous domain. Non-reduced chimeric proteins formed predominantly nona- and dodecameric oligomers, whereas recombinant human MBL formed octadecameric and larger oligomers. Surface plasmon resonance revealed that L-FCN/MBL76 had the highest binding affinities for N-acetylglucosamine-bovine serum albumin and mannan. The same chimeric protein displayed superior complement C4 cleavage and binding to calreticulin (cC1qR), a putative receptor for MBL. L-FCN/MBL76 reduced infection by wild type Ebola virus Zaire significantly greater than the other molecules. Tapping mode atomic force microscopy revealed that L-FCN/MBL76 was significantly less tall than the other molecules despite similar polypeptide lengths. We propose that alterations in the quaternary structure of L-FCN/MBL76 resulted in greater flexibility in the collagenous or neck region. Similarly, a more pliable molecule might enhance cooperativity between the carbohydrate recognition domains and their cognate ligands, complement activation, and calreticulin binding dynamics. L-FCN/MBL chimeric proteins should be considered as potential novel therapeutics.",,"['Michelow, Ian C.', 'Dong, Mingdong', 'Mungall, Bruce A.', 'Yantosca, L. Michael', 'Lear, Calli', 'Ji, Xin', 'Karpel, Marshall', 'Rootes, Christina L.', 'Brudner, Matthew', 'Houen, Gunnar', 'Eisen, Damon P.', 'Kinane, T. Bernard', 'Takahashi, Kazue', 'Stahl, Gregory L.', 'Olinger, Gene G.', 'Spear, Gregory T.', 'Ezekowitz, R. Alan B.', 'Schmidt, Emmett V.']",,,,
,PMC,"Human bocaviruses are highly diverse, dispersed, recombination prone, and prevalent enteric infections",http://dx.doi.org/10.1086/652416,PMC2902747,,,"A new species of parvovirus tentatively named human bocavirus 4 (HBoV4) was genetically characterized. Among 641 feces samples from children and adults the most commonly detected bocaviruses species were HBoV2>HBoV3>HBoV4>HBoV1 with HBoV2 prevalence of 21% and 26% in Nigerian and Tunisian children. HBoV3 and HBoV4 species combined were found in 12/192 cases of non-polio acute flaccid paralysis (AFP) from Tunisia and Nigeria and 0/96 healthy Tunisian contacts (p=0.01). Evidence of extensive recombination at the NP1 and VP1 gene boundary between and within species was found. The multiple species and high degree of genetic diversity seen among the human bocaviruses found in feces relative to the highly homogeneous HBoV1 suggest that this world-wide distributed respiratory pathogen may have recently evolved from an enteric bocavirus, perhaps after acquiring an expanded tropism favoring the respiratory track. Elucidating the possible role of the newly identified enteric bocaviruses in human diseases including AFP and diarrhea will require further epidemiological studies.",,"['Kapoor, A', 'Simmonds, P.', 'Slikas, B.', 'Li, Linlin', 'Bodhidatta, L.', 'Sethabutr, O.', 'Triki, H.', 'Bahri, Olfa', 'Oderinde, B.', 'Baba, M.', 'Bukbuk, D.', 'Besser, J.', 'Bartkus, J.', 'Delwart, E.']",,,,
,PMC,FREQUENT AND PROLONGED SHEDDING OF BOCAVIRUS IN YOUNG CHILDREN ATTENDING DAYCARE,http://dx.doi.org/10.1086/652405,PMC2862123,,,"BACKGROUND: Little is known about HBoV persistence and shedding and the association between HBoV detection and the onset and resolution of respiratory symptoms. METHODS: We performed HBoV testing on nasal swabs from a prospective, longitudinal study of respiratory illness in 119 children attending daycare. RESULTS: HBoV was detected in 70 children (59%), and in 106 (33%) of the 318 study illnesses. Another virus was detected in 76 HBoV+ illnesses (72%). Extended and intermittent shedding was observed, with consistent HBoV detection documented for up to 75 days. HBoV was detected in 20 of 45 asymptomatic enrollment samples (44%) and HBoV prevalence and viral load did not differ significantly between children with and without symptoms at enrollment. HBoV+ illnesses were longer than HBoV- illnesses (OR: 2.44 for symptoms > 7 days, 95% C.I. 1.41, 4.22) and illnesses with HBoV viral load ≥ 4 log-copies/mL required a visit to a health care provider more often than HBoV-illnesses (OR: 1.64, 95% C.I.: 1.02, 2.64). CONCLUSION: HBoV was more common in illnesses with greater severity. However, detection of HBoV was not associated with the presence of respiratory illness or with specific respiratory symptoms in this prospective study of infants and toddlers attending center-based daycare.",,"['Martin, Emily T.', 'Fairchok, Mary P.', 'Kuypers, Jane', 'Magaret, Amalia', 'Zerr, Danielle M.', 'Wald, Anna', 'Englund, Janet A.']",,,,
,PMC,Déjà vu All Over Again: Koch's Postulates and Virology in the 21(st) Century,http://dx.doi.org/10.1086/652406,PMC2862077,,,,,"Williams., John V.",,,,
,PMC,A role of apolipoprotein D in triglyceride metabolism,http://dx.doi.org/10.1194/jlr.M001206,PMC3035493,,,"Apolipoproteins (apo) are constituents of lipoproteins crucial for lipid homeostasis. Aberrant expression of apolipoproteins is associated with metabolic abnormalities. Here we characterized apolipoprotein D (apoD) in triglyceride metabolism. Unlike canonical apolipoproteins that are mainly produced in the liver, apoD is an atypical apolipoprotein with broad tissue distribution. We show that circulating apoD is present mainly in HDL and, to a lesser extent, in LDL and VLDL and that its plasma levels were reduced in db/db mice with visceral obesity and altered lipid metabolism. Elevated apoD production, derived from adenovirus-mediated gene transfer, resulted in significant reduction in plasma triglyceride levels in mice. This effect was attributable to en­hanced LPL activity and improved catabolism of triglyceride-rich particles. In contrast, VLDL triglyceride production remained unchanged in response to elevated apoD production. These findings were recapitulated in high-fat–induced obese mice. Obese mice with elevated apoD production exhibited significantly improved triglyceride profiles, correlating with increased plasma LPL activity and enhanced postprandial fat tolerance. ApoD was shown to promote LPL-mediated hydrolysis of VLDL in vitro, correlating with its TG-lowering action in vivo. Apolipoprotein D plays a significant role in lipid metabolism. These data provide important clues to clinical observations that genetic variants of apoD are associated with abnormal lipid metabolism and increased risk of metabolic syndrome.",,"['Perdomo, German', 'Kim, Dae Hyun', 'Zhang, Ting', 'Qu, Shen', 'Thomas, Elizabeth A.', 'Toledo, Frederico G. S.', 'Slusher, Sandra', 'Fan, Yong', 'Kelley, David E.', 'Dong, H. Henry']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00840-10,PMC2876655,,,,,,,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00743-10,PMC2876619,,,,,,,,,
,PMC,Evidence-Based Point-of-Care Device Design for Emergency and Disaster Care,http://dx.doi.org/10.1097/POC.0b013e3181d9d47a,PMC2883177,,,,,"['Mecozzi, Daniel M.', 'Brock, T. Keith', 'Tran, Nam K.', 'Hale, Kristin N.', 'Kost, Gerald J.']",,,,
,PMC,Migration of engrafted neural stem cells is mediated by CXCL12 signaling through CXCR4 in a viral model of multiple sclerosis,http://dx.doi.org/10.1073/pnas.1006375107,PMC2890772,,,"Multiple sclerosis (MS) is a human demyelinating disease characterized by multifocal regions of inflammation, progressive myelin loss within the central nervous system (CNS), and eventual failure to remyelinate damaged axons. These problems suggest deficiencies in recruiting and/or maturation of oligodendrocyte progentior cells (OPCs) and highlight cell replacement therapies to promote remyelination. We have used a model of viral-induced demyelination to characterize signaling cues associated with positional migration of transplanted remyelination-competent cells. Although successful transplantation of rodent-derived glial cell types into models of MS has been performed, the mechanisms by which these cells navigate within an inflammatory environment created by a persistent virus has not been defined. Infection of the mouse CNS with the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in an immune-mediated demyelinating disease with clinical and histologic similarities to MS. Surgical engraftment of GFP+ neural stem cells (NSCs) into spinal cords of JHMV-infected mice with established demyelination results in migration, proliferation, and differentiation of the cells into OPCs and mature oligodendrocytes that is associated with increased axonal remyelination. Treatment with anti-CXCL12 [stromal derived factor–1α, (SDF-1α)] blocking serum resulted in a marked impairment in migration and proliferation of engrafted stem cells. Moreover, small molecule–mediated antagonism of CXCR4, but not CXCR7, impaired migration and proliferation, to an extent similar to that with anti-CXCL12 treatment. These data highlight the importance of the CXCL12:CXCR4 pathway in regulating homing of engrafted stem cells to sites of tissue damage within the CNS of mice persistently infected with a neurotropic virus undergoing immune-mediated demyelination.",,"['Carbajal, Kevin S.', 'Schaumburg, Christopher', 'Strieter, Robert', 'Kane, Joy', 'Lane, Thomas E.']",,,,
,PMC,Identification of ciliary neurotrophic factor receptor alpha as a mediator of neurotoxicity induced by α-synuclein,http://dx.doi.org/10.1002/pmic.200900745,PMC3013276,,,"Accumulating evidence suggests that extracellular α-synuclein (eSNCA) plays an important role in the pathogenesis of Parkinson's disease (PD) or related synucleinopathies by inducing neurotoxicity directly or indirectly via microglial or astroglial activation. However, the mechanisms by which this occurs remain to be characterized. To explore these mechanisms, we combined three biochemical techniques - Stable Isotope Labeling of Amino acid in Cell cultures (SILAC); biotin labeling of plasma membrane proteins followed by affinity purification; and analysis of unique proteins binding to SNCA peptides on membrane arrays. The SILAC proteomic analysis identified 457 proteins, of which, 245 or 172 proteins belonged to membrane or membrane associated proteins, depending on the various bioinformatics tools used for interpretation. In dopamine neuronal cells treated with eSNCA, the levels of 86 membrane proteins were increased and 35 were decreased compared with untreated cells. In peptide array analysis, 127 proteins were identified as possibly interacting with eSNCA. Of those, seven proteins were overlapped with the membrane proteins that displayed alterations in relative abundance after eSNCA treatment. One was ciliary neurotrophic factor receptor alpha (CNTFR-α), which appeared to modulate eSNCA-mediated neurotoxicity via mechanisms related to JAK1/STAT3 signaling but independent of eSNCA endocytosis.",,"['Liu, Jun', 'Shi, Min', 'Hong, Zhen', 'Zhang, JianPeng', 'Bradner, Joshua', 'Quinn, Thomas', 'Beyer, Richard P.', 'Mcgeer, Patrick L.', 'Chen, ShengDi', 'Zhang, Jing']",,,,
,PMC,Stimulation of −1 programmed ribosomal frameshifting by a metabolite-responsive RNA pseudoknot,http://dx.doi.org/10.1261/rna.1922410,PMC2874175,,,"Specific recognition of metabolites by functional RNA motifs within mRNAs has emerged as a crucial regulatory strategy for feedback control of biochemical reactions. Such riboswitches have been demonstrated to regulate different gene expression processes, including transcriptional termination and translational initiation in prokaryotic cells, as well as splicing in eukaryotic cells. The regulatory process is usually mediated by modulating the accessibility of specific sequence information of the expression platforms via metabolite-induced RNA conformational rearrangement. In eukaryotic systems, viral and the more limited number of cellular decoding −1 programmed ribosomal frameshifting (PRF) are commonly promoted by a 3′ mRNA pseudoknot. In addition, such −1 PRF is generally constitutive rather than being regulatory, and usually results in a fixed ratio of products. We report here an RNA pseudoknot capable of stimulating −1 PRF whose efficiency can be tuned in response to the concentration of S-adenosylhomocysteine (SAH), and the improvement of its frameshifting efficiency by RNA engineering. In addition to providing an alternative approach for small-molecule regulation of gene expression in eukaryotic cells, such a metabolite-responsive pseudoknot suggests a plausible mechanism for metabolite-driven translational regulation of gene expression in eukaryotic systems.",,"['Chou, Ming-Yuan', 'Lin, Szu-Chieh', 'Chang, Kung-Yao']",,,,
,PMC,Crystallization and preliminary X-ray diffraction studies of infectious bronchitis virus nonstructural protein 9,http://dx.doi.org/10.1107/S174430911001417X,PMC2882775,,,"Avian infectious bronchitis virus (IBV), which causes respiratory disease in infected birds, belongs to coronavirus group 3. IBV encodes 15 nonstructural proteins (nsp2–nsp16) which play crucial roles in RNA transcription and genome replication. Nonstructural protein 9 (nsp9) has been identified as a protein that is essential to viral replication because of its single-stranded RNA-binding ability. The gene segment encoding IBV nsp9 has been cloned and expressed in Escherichia coli. The protein has been crystallized and the crystals diffracted X-rays to 2.44 Å resolution. They belonged to the cubic space group I432, with unit-cell parameters a = b = c = 123.4 Å, α = β = γ = 90°. The asymmetric unit appeared to contain one molecule, with a solvent content of 62% (V (M) = 3.26 Å(3) Da(−1)).",,"['Ma, Yanlin', 'Chen, Cheng', 'Wei, Lei', 'Yang, Qingzhu', 'Liao, Ming', 'Li, Xuemei']",,,,
,PMC,GANP-mediated Recruitment of Activation-induced Cytidine Deaminase to Cell Nuclei and to Immunoglobulin Variable Region DNA,http://dx.doi.org/10.1074/jbc.M110.131441,PMC2911284,,,"AID (activation-induced cytidine deaminase) catalyzes transcription-dependent deamination of C → U in immunoglobulin variable (IgV) regions to initiate somatic hypermutation (SHM) in germinal center B-cells. SHM is essential in generating high affinity antibodies. Here we show that when coexpressed with GANP (germinal center-associated nuclear protein) in COS-7 cells, AID is transported from the cytoplasm and concentrated in the nucleus. GANP forms a complex with AID in cotransfected cells in vivo and in vitro. We have isolated AID mutants that bind with reduced affinity to GANP compared with wild type AID. One of these mutants, AID (D143A) binds GANP with a 10-fold lower affinity compared with wild type AID yet retains substantial C-deamination activity in vitro. Mutant AID (D143A) remains localized predominantly in the cytoplasm when coexpressed with GANP. Exogenous expression of GANP in Ramos B-cells promotes binding of AID to IgV DNA and mRNA and increases SHM frequency. These data suggest that GANP may serve as an essential link required to transport AID to B-cell nuclei and to target AID to actively transcribed IgV regions.",,"['Maeda, Kazuhiko', 'Singh, Shailendra Kumar', 'Eda, Kazufumi', 'Kitabatake, Masahiro', 'Pham, Phuong', 'Goodman, Myron F.', 'Sakaguchi, Nobuo']",,,,
,PMC,"Expression, crystallization and preliminary crystallographic study of mouse hepatitis virus (MHV) nucleocapsid protein C-terminal domain",http://dx.doi.org/10.1107/S1744309110012492,PMC2882767,,,"Mouse hepatitis virus (MHV) belongs to the group II coronaviruses. The virus produces nine genes encoding 11 proteins that could be recognized as structural proteins and nonstructural proteins and are crucial for viral RNA synthesis. The nucleocapsid (N) protein, one of the structural proteins, interacts with the 30.4 kb virus genomic RNA to form the helical nucleocapsid and associates with the membrane glycoprotein via its C-terminus to stabilize virion assembly. Here, the expression and crystallization of the MHV nucleocapsid protein C-terminal domain are reported. The crystals diffracted to 2.20 Å resolution and belonged to space group P422, with unit-cell parameters a = 66.6, c = 50.8 Å. Assuming the presence of two molecules in the asymmetric unit, the solvent content is 43.0% (V (M) = 2.16 Å(3) Da(−1)).",,"['Tong, Xiaohang', 'Ma, Yanlin', 'Li, Xuemei']",,,,
,PMC,Retinal pathology in multiple sclerosis: insight into the mechanisms of neuronal pathology,http://dx.doi.org/10.1093/brain/awq133,PMC2877908,,,,,"['Calabresi, Peter A.', 'Balcer, Laura J.', 'Frohman, Elliot M.']",,,,
,PMC,Modelling the influence of human behaviour on the spread of infectious diseases: a review,http://dx.doi.org/10.1098/rsif.2010.0142,PMC2894894,,,"Human behaviour plays an important role in the spread of infectious diseases, and understanding the influence of behaviour on the spread of diseases can be key to improving control efforts. While behavioural responses to the spread of a disease have often been reported anecdotally, there has been relatively little systematic investigation into how behavioural changes can affect disease dynamics. Mathematical models for the spread of infectious diseases are an important tool for investigating and quantifying such effects, not least because the spread of a disease among humans is not amenable to direct experimental study. Here, we review recent efforts to incorporate human behaviour into disease models, and propose that such models can be broadly classified according to the type and source of information which individuals are assumed to base their behaviour on, and according to the assumed effects of such behaviour. We highlight recent advances as well as gaps in our understanding of the interplay between infectious disease dynamics and human behaviour, and suggest what kind of data taking efforts would be helpful in filling these gaps.",,"['Funk, Sebastian', 'Salathé, Marcel', 'Jansen, Vincent A. A.']",,,,
,PMC,The Cysteine Protease Domain of Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 2 Possesses Deubiquitinating and Interferon Antagonism Functions,http://dx.doi.org/10.1128/JVI.00217-10,PMC2897636,,,"Porcine reproductive and respiratory syndrome (PRRS) virus nonstructural protein 2 (nsp2) contains a cysteine protease domain at its N terminus, which belongs to the ovarian tumor (OTU) protease family. In this study, we demonstrated that the PRRSV nsp2 OTU domain antagonizes the type I interferon induction by interfering with the NF-κB signaling pathway. Further analysis revealed that the nsp2 OTU domain possesses ubiquitin-deconjugating activity. This domain has the ability to inhibit NF-κB activation by interfering with the polyubiquitination process of IκBα, which subsequently prevents IκBα degradation. To determine whether the nsp2 protein antagonist function can be ablated from the virus, we introduced point mutations into the OTU domain region by use of reverse genetics. The D458A, S462A, and D465A mutations targeting on a B-cell epitope in the OTU domain region generated the viable recombinant viruses, and the S462A and D465A mutants were attenuated for growth in cell culture. The OTU domain mutants were examined to determine whether mutations in the nsp2 OTU domain region altered virus ability to inhibit NF-κB activation. The result showed that certain mutations lethal to virus replication impaired the ability of nsp2 to inhibit NF-κB activation but that the viable recombinant viruses, vSD-S462A and vSD-D465A, were unable to inhibit NF-κB activation as effectively as the wild-type virus. This study represents a fundamental step in elucidating the role of nsp2 in PRRS pathogenesis and provides an important insight in future modified live-virus vaccine development.",,"['Sun, Zhi', 'Chen, Zhenhai', 'Lawson, Steven R.', 'Fang, Ying']",,,,
,PMC,Viral etiology of severe pneumonia among Kenyan young infants and children,http://dx.doi.org/10.1001/jama.2010.675,PMC2968755,,,"CONTEXT: Pneumonia is the leading cause of childhood death in sub-Saharan Africa. Comparative estimates of the contribution of causative pathogens to the burden of disease are essential for targeted vaccine development. OBJECTIVE: To determine the viral etiology of severe pneumonia among infants and children at a rural Kenyan hospital using comprehensive and sensitive molecular diagnostic techniques. DESIGN, SETTING & PARTICIPANTS: Prospective observational and case control study during 2007 in a rural Kenyan district hospital. We recruited children age 1 day to 12 years who were resident in a systematically enumerated catchment area: i) those admitted to Kilifi District Hospital meeting WHO clinical criteria for ‘severe pneumonia’ or ‘very severe pneumonia’; ii) those presenting with mild upper respiratory tract infection but not admitted and iii) well infants and children attending for immunization. MAIN OUTCOME MEASURES: The presence of respiratory viruses and the odds ratio for admission with severe disease. RESULTS: 759/922 (83%) eligible admissions were sampled (median age 9 months). One or more respiratory viruses were detected in 425/759 (56%, 95% CI 52 to 60%). Respiratory syncytial virus (RSV) was detected in 260 (34%, 95% CI 31 to 38%) and other respiratory viruses in 219 (29%, 95% CI 26 to 32%), the commonest being human coronavirus 229E (n=51, 6.7%, 95% CI 5.0 to 8.7%), influenza type A (n=44, 5.8%, 95% CI 4.2 to 7.7%), parainfluenza type 3 (n=29, 3.8%, 95% CI 2.6 to 5.4%), adenovirus (n=29, 3.8%, 95% CI 2.6 to 5.4%) and human metapneumovirus (n=23, 3.0%, 95% CI 1.9 to 4.5%). Compared to well controls, detection of RSV was associated with severe disease (4% in controls, adjusted odds Ratio 6.11 [95% CI 1.65 to 22.6]) whilst collectively, other respiratory viruses were not (23% in controls, adjusted odds Ratio 1.27 [95% CI 0.64 to 2.52]). CONCLUSIONS: In a sample of Kenyan infants and children admitted with severe pneumonia to a rural hospital, RSV was the predominant viral pathogen.",,"['Berkley, James A', 'Munywoki, Patrick', 'Ngama, Mwanajuma', 'Kazungu, Sidi', 'Abwao, John', 'Bett, Anne', 'Lassauniére, Ria', 'Kresfelder, Tina', 'Cane, Patricia A', 'Venter, Marietjie', 'Scott, J Anthony G', 'Nokes, D James']",,,,
,PMC,Emerging studies of human HIV-specific antibody repertoires,http://dx.doi.org/10.1016/j.vaccine.2010.02.002,PMC2879399,,,"There has been an explosion of interest in the human B cell response to HIV infection of late. Recent advances in techniques for isolation of human antibodies and antibody secreting cell lines have facilitated a rapid expansion in the number of antibodies available for study. Early analysis of these repertoires reveals interesting features of the HIV-specific antibody response. HIV-specific repertoires exhibit a high level of clonality in circulating cells, and high levels of somatic mutations within the antibody variable gene segments. It appears that many if not most antibodies in circulation bind to virus envelope conformations that are found only in complex oligomeric structures on virion particles or virus-like particles. The rapid isolation of large panels of novel human neutralizing antibodies promises to reveal new insights into the fundamental principles underlying antibody-mediated neutralization of HIV.",,"['Hicar, Mark D.', 'Kalams, Spyros A.', 'Spearman, Paul W.', 'Crowe, James E.']",,,,
,PMC,Mutation of Asn28 disrupts the dimerization and enzymatic activity of SARS 3CL(pro),http://dx.doi.org/10.1021/bi1002585,PMC2877132,,,"Coronaviruses are responsible for a significant proportion of annual respiratory and enteric infections in humans and other mammals. The most prominent of these viruses is the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) which causes acute respiratory and gastrointestinal infection in humans. The coronavirus main protease, 3CL(pro), is a key target for broad-spectrum antiviral development due to its critical role in viral maturation and high degree of structural conservation among coronaviruses. Dimerization is an indispensable requirement for the function of SARS 3CL(pro) and is regulated through mechanisms involving both direct and long-range interactions in the enzyme. While many of the binding interactions at the dimerization interface have been extensively studied, those that are important for long-range control are not well understood. Characterization of these dimerization mechanisms is important for the structure-based design of new treatments targeting coronavirus-based infections. Here we report that Asn28, a residue located 11 Å away from the closest residue in the opposing monomer, is essential for the enzymatic activity and dimerization of SARS 3CL(pro). Mutation of this residue to alanine almost completely inactivates the enzyme and results in a 19.2-fold decrease in the dimerization K(d). The crystallographic structure of the N28A mutant determined at a 2.35 Å resolution reveals the critical role of Asn28 in maintaining the structural integrity of the active site and in orienting key residues involved in binding at the dimer interface and substrate catalysis. These findings provide a deeper insight into complex mechanisms regulating the activity and dimerization of SARS 3CL(pro).",,"['Barrila, Jennifer', 'Gabelli, Sandra B.', 'Bacha, Usman', 'Amzel, L. Mario', 'Freire, Ernesto']",,,,
,PMC,SARS Coronavirus-unique Domain (SUD): Three-domain Molecular Architecture in Solution and RNA Binding,http://dx.doi.org/10.1016/j.jmb.2010.05.027,PMC2958096,,,"The nonstructural protein 3 (nsp3) of the severe acute respiratory syndrome coronavirus (SARS-CoV) includes a “SARS-unique region” (SUD) consisting of three globular domains separated by short linker peptide segments. This paper reports NMR structure determinations of the C-terminal domain (SUD-C) and of a two-domain construct (SUD-MC) containing the middle domain (SUD-M) and the C-terminal domain, and NMR data on the conformational states of the N-terminal domain (SUD-N) and the SUD-NM two-domain construct. Both SUD-N and SUD-NM are monomeric and globular in solution, and in SUD-NM there is high mobility in the two-residue interdomain linking sequence, with no preferred relative orientation of the two domains. SUD-C adopts a frataxin-like fold and has structural similarity to DNA-binding domains of DNA-modifying enzymes. The structures of both SUD-M (previously determined) and SUD-C (from the present study) are maintained in SUD-MC, where the two domains are flexibly linked. Gel shift experiments showed that both SUD-C and SUD-MC bind to single-stranded RNA and recognize purine bases more strongly than pyrimidine bases, whereby SUD-MC binds to a more restricted set of purine-containing RNA sequences than SUD-M. NMR chemical shift perturbation experiments with observation of the (15)N-labeled proteins further resulted in the delineation of the RNA binding sites, i.e., in SUD-M a positively charged surface area with a pronounced cavity, and in SUD-C several residues of an antiparallel β-sheet. Overall, the present data provide evidence for molecular mechanisms involving concerted actions of SUD-M and SUD-C, which result in specific RNA-binding that might be unique to the SUD, and thus to the SARS-CoV.",,"['Johnson, Margaret A.', 'Chatterjee, Amarnath', 'Neuman, Benjamin W.', 'Wüthrich, Kurt']",,,,
,PMC,Maturation Mechanism of Severe Acute Respiratory Syndrome (SARS) Coronavirus 3C-like Proteinase,http://dx.doi.org/10.1074/jbc.M109.095851,PMC2934678,,,"The 3C-like proteinase (3CL(pro)) of the severe acute respiratory syndrome (SARS) coronavirus plays a vital role in virus maturation and is proposed to be a key target for drug design against SARS. Various in vitro studies revealed that only the dimer of the matured 3CL(pro) is active. However, as the internally encoded 3CL(pro) gets matured from the replicase polyprotein by autolytic cleavage at both the N-terminal and the C-terminal flanking sites, it is unclear whether the polyprotein also needs to dimerize first for its autocleavage reaction. We constructed a large protein containing the cyan fluorescent protein (C), the N-terminal flanking substrate peptide of SARS 3CL(pro) (XX), SARS 3CL(pro) (3CLP), and the yellow fluorescent protein (Y) to study the autoprocessing of 3CL(pro) using fluorescence resonance energy transfer. In contrast to the matured 3CL(pro), the polyprotein, as well as the one-step digested product, 3CLP-Y-His, were shown to be monomeric in gel filtration and analytic ultracentrifuge analysis. However, dimers can still be induced and detected when incubating these large proteins with a substrate analog compound in both chemical cross-linking experiments and analytic ultracentrifuge analysis. We also measured enzyme activity under different enzyme concentrations and found a clear tendency of substrate-induced dimer formation. Based on these discoveries, we conclude that substrate-induced dimerization is essential for the activity of SARS-3CL(pro) in the polyprotein, and a modified model for the 3CL(pro) maturation process was proposed. As many viral proteases undergo a similar maturation process, this model might be generally applicable.",,"['Li, Chunmei', 'Qi, Yifei', 'Teng, Xin', 'Yang, Zongchang', 'Wei, Ping', 'Zhang, Changsheng', 'Tan, Lei', 'Zhou, Lu', 'Liu, Ying', 'Lai, Luhua']",,,,
,PMC,IL-2 and IL-10 gene polymorphisms are associated with respiratory tract infection and may modulate the effect of vitamin E on lower respiratory tract infections in elderly nursing home residents(1)(2)(3)(4),http://dx.doi.org/10.3945/ajcn.2010.29207,PMC2884322,,,"Background: Vitamin E supplementation may be a potential strategy to prevent respiratory tract infections (RIs) in the elderly. The efficacy of vitamin E supplementation may depend on individual factors including specific single nucleotide polymorphisms (SNPs) at immunoregulatory genes. Objective: We examined whether the effect of vitamin E on RIs in the elderly was dependent on genetic backgrounds as indicated by SNPs at cytokine genes. Design: We used data and DNA from a previous vitamin E intervention study (200 IU vitamin E or a placebo daily for 1 y) in elderly nursing home residents to examine vitamin E–gene interactions for incidence of RI. We determined the genotypes of common SNPs at IL-1β, IL-2, IL-6, IL-10, TNF-α, and IFN-γ in 500 participants. We used negative binomial regression to analyze the association between genotype and incidence of infection. Results: The effect of vitamin E on lower RI depended on sex and the SNP at IL-10 −819G→A (P = 0.03 for interaction for lower RI). Furthermore, we observed that subjects with the least prevalent genotypes at IL-2 −330A→C (P = 0.02 for upper RI), IL-10 −819G→A (P = 0.08 for upper RI), and IL-10 −1082C→T (P < 0.001 for lower RI in men) had a lower incidence of RI independent of vitamin E supplementation. Conclusions: Studies that evaluate the effect of vitamin E on RIs should consider both genetic factors and sex because our results suggest that both may have a significant bearing on the efficacy of vitamin E. Furthermore, common SNPs at cytokine genes may contribute to the individual risk of RIs in the elderly. This trial was registered at clinicaltrials.gov as NCT00758914.",,"['Belisle, Sarah E', 'Hamer, Davidson H', 'Leka, Lynette S', 'Dallal, Gerard E', 'Delgado-Lista, Javier', 'Fine, Basil C', 'Jacques, Paul F', 'Ordovas, Jose M', 'Meydani, Simin Nikbin']",,,,
,PMC,Outbreak of Canine Norovirus Infection in Young Dogs,http://dx.doi.org/10.1128/JCM.02528-09,PMC2897520,,,"An outbreak of norovirus (NoV) infection was identified in a kennel. Sequence analysis of a short fragment in the polymerase complex indicated the clonal origin of the strains, which were similar to the prototype canine NoV strain GIV.2/Bari/170/07-4/ITA (94.7% nucleotide identity). The findings demonstrate that canine NoV circulates in dogs in Greece and that it can spread easily across a group of animals.",,"['Ntafis, Vasileios', 'Xylouri, Eftychia', 'Radogna, Arianna', 'Buonavoglia, Canio', 'Martella, Vito']",,,,
,PMC,Redirecting Lentiviral Vectors Pseudotyped with Sindbis Virus-Derived Envelope Proteins to DC-SIGN by Modification of N-Linked Glycans of Envelope Proteins,http://dx.doi.org/10.1128/JVI.00435-10,PMC2898243,,,"Redirecting the tropism of viral vectors enables specific transduction of selected cells by direct administration of vectors. We previously developed targeting lentiviral vectors by pseudotyping with modified Sindbis virus envelope proteins. These modified Sindbis virus envelope proteins have mutations in their original receptor-binding regions to eliminate their natural tropisms, and they are conjugated with targeting proteins, including antibodies and peptides, to confer their tropisms on target cells. We investigated whether our targeting vectors interact with DC-SIGN, which traps many types of viruses and gene therapy vectors by binding to the N-glycans of their envelope proteins. We found that these vectors do not interact with DC-SIGN. When these vectors were produced in the presence of deoxymannojirimycin, which alters the structures of N-glycans from complex to high mannose, these vectors used DC-SIGN as their receptor. Genetic analysis demonstrated that the N-glycans at E2 amino acid (aa) 196 and E1 aa 139 mediate binding to DC-SIGN, which supports the results of a previous report of cryoelectron microscopy analysis. In addition, we investigated whether modification of the N-glycan structures could activate serum complement activity, possibly by the lectin pathway of complement activation. DC-SIGN-targeted transduction occurs in the presence of human serum complement, demonstrating that high-mannose structure N-glycans of the envelope proteins do not activate human serum complement. These results indicate that the strategy of redirecting viral vectors according to alterations of their N-glycan structures would enable the vectors to target specific cells types expressing particular types of lectins.",,"['Morizono, Kouki', 'Ku, Amy', 'Xie, Yiming', 'Harui, Airi', 'Kung, Sam K. P.', 'Roth, Michael D.', 'Lee, Benhur', 'Chen, Irvin S. Y.']",,,,
,PMC,The Proteasome Inhibitor Velcade Enhances rather than Reduces Disease in Mouse Hepatitis Coronavirus-Infected Mice,http://dx.doi.org/10.1128/JVI.00486-10,PMC2897637,,,"Many viruses, including coronaviruses (CoVs), depend on a functional cellular proteasome for efficient infection in vitro. Hence, the proteasome inhibitor Velcade (bortezomib), a clinically approved anticancer drug, shown in an accompanying study (M. Raaben et al., J. Virol. 84:7869-7879, 2010) to strongly inhibit mouse hepatitis CoV (MHV) infection in cultured cells, seemed an attractive candidate for testing its antiviral properties in vivo. Surprisingly, however, the drug did not reduce replication of the virus in mice. Rather, inhibition of the proteasome caused enhanced infection with lethal outcome, calling for caution when using this type of drug during infection.",,"['Raaben, Matthijs', 'Grinwis, Guy C. M.', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.']",,,,
,PMC,Tyrosine Residues in the Cytoplasmic Domains Affect Sorting and Fusion Activity of the Nipah Virus Glycoproteins in Polarized Epithelial Cells,http://dx.doi.org/10.1128/JVI.02576-09,PMC2897613,,,"The highly pathogenic Nipah virus (NiV) is aerially transmitted and causes a systemic infection after entering the respiratory tract. Airway epithelia are thus important targets in primary infection. Furthermore, virus replication in the mucosal surfaces of the respiratory or urinary tract in later phases of infection is essential for virus shedding and transmission. So far, the mechanisms of NiV replication in epithelial cells are poorly elucidated. In the present study, we provide evidence that bipolar targeting of the two NiV surface glycoproteins G and F is of biological importance for fusion in polarized epithelia. We demonstrate that infection of polarized cells induces focus formation, with both glycoproteins located at lateral membranes of infected cells adjacent to uninfected cells. Supporting the idea of a direct spread of infection via lateral cell-to-cell fusion, we could identify basolateral targeting signals in the cytoplasmic domains of both NiV glycoproteins. Tyrosine 525 in the F protein is part of an endocytosis signal and is also responsible for basolateral sorting. Surprisingly, we identified a dityrosine motif at position 28/29 in the G protein, which mediates polarized targeting. A dileucine motif predicted to function as sorting signal is not involved. Mutation of the targeting signal in one of the NiV glycoproteins prevented the fusion of polarized cells, suggesting that basolateral or bipolar F and G expression facilitates the spread of NiV within epithelial cell monolayers, thereby contributing to efficient virus spread in mucosal surfaces in early and late phases of infection.",,"['Weise, Carolin', 'Erbar, Stephanie', 'Lamp, Boris', 'Vogt, Carola', 'Diederich, Sandra', 'Maisner, Andrea']",,,,
,PMC,Feline Lectin Activity Is Critical for the Cellular Entry of Feline Infectious Peritonitis Virus,http://dx.doi.org/10.1128/JVI.00964-10,PMC2897608,,,"Feline infectious peritonitis is a lethal disease of felids caused by systemic infection with a feline coronavirus. Here, we report identification and analysis of the feline homologue to the human lectin DC-SIGN and show that it is a coreceptor for virulent strains of serotype 1 and serotype 2 feline coronaviruses.",,"['Regan, Andrew D.', 'Ousterout, David G.', 'Whittaker, Gary R.']",,,,
,PMC,"Phosphatidylinositol 3-Kinase-, Actin-, and Microtubule-Dependent Transport of Semliki Forest Virus Replication Complexes from the Plasma Membrane to Modified Lysosomes",http://dx.doi.org/10.1128/JVI.00477-10,PMC2897599,,,"Like other positive-strand RNA viruses, alphaviruses replicate their genomes in association with modified intracellular membranes. Alphavirus replication sites consist of numerous bulb-shaped membrane invaginations (spherules), which contain the double-stranded replication intermediates. Time course studies with Semliki Forest virus (SFV)-infected cells were combined with live-cell imaging and electron microscopy to reveal that the replication complex spherules of SFV undergo an unprecedented large-scale movement between cellular compartments. The spherules first accumulated at the plasma membrane and were then internalized using an endocytic process that required a functional actin-myosin network, as shown by blebbistatin treatment. Wortmannin and other inhibitors indicated that the internalization of spherules also required the activity of phosphatidylinositol 3-kinase. The spherules therefore represent an unusual type of endocytic cargo. After endocytosis, spherule-containing vesicles were highly dynamic and had a neutral pH. These primary carriers fused with acidic endosomes and moved long distances on microtubules, in a manner prevented by nocodazole. The result of the large-scale migration was the formation of a very stable compartment, where the spherules were accumulated on the outer surfaces of unusually large and static acidic vacuoles localized in the pericentriolar region. Our work highlights both fundamental similarities and important differences in the processes that lead to the modified membrane compartments in cells infected by distinct groups of positive-sense RNA viruses.",,"['Spuul, Pirjo', 'Balistreri, Giuseppe', 'Kääriäinen, Leevi', 'Ahola, Tero']",,,,
,PMC,The Ubiquitin-Proteasome System Plays an Important Role during Various Stages of the Coronavirus Infection Cycle,http://dx.doi.org/10.1128/JVI.00485-10,PMC2897594,,,"The ubiquitin-proteasome system (UPS) is a key player in regulating the intracellular sorting and degradation of proteins. In this study we investigated the role of the UPS in different steps of the coronavirus (CoV) infection cycle. Inhibition of the proteasome by different chemical compounds (i.e., MG132, epoxomicin, and Velcade) appeared to not only impair entry but also RNA synthesis and subsequent protein expression of different CoVs (i.e., mouse hepatitis virus [MHV], feline infectious peritonitis virus, and severe acute respiratory syndrome CoV). MHV assembly and release were, however, not appreciably affected by these compounds. The inhibitory effect on CoV protein expression did not appear to result from a general inhibition of translation due to induction of a cellular stress response by the inhibitors. Stress-induced phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) generally results in impaired initiation of protein synthesis, but the sensitivity of MHV infection to proteasome inhibitors was unchanged in cells lacking a phosphorylatable eIF2α. MHV infection was affected not only by inhibition of the proteasome but also by interfering with protein ubiquitination. Viral protein expression was reduced in cells expressing a temperature-sensitive ubiquitin-activating enzyme E1 at the restrictive temperature, as well as in cells in which ubiquitin was depleted by using small interfering RNAs. Under these conditions, the susceptibility of the cells to virus infection was, however, not affected, excluding an important role of ubiquitination in virus entry. Our observations reveal an important role of the UPS in multiple steps of the CoV infection cycle and identify the UPS as a potential drug target to modulate the impact of CoV infection.",,"['Raaben, Matthijs', 'Posthuma, Clara C.', 'Verheije, Monique H.', 'te Lintelo, Eddie G.', 'Kikkert, Marjolein', 'Drijfhout, Jan W.', 'Snijder, Eric J.', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.']",,,,
,PMC,Upregulation of the Chemokine (C-C Motif) Ligand 2 via a Severe Acute Respiratory Syndrome Coronavirus Spike-ACE2 Signaling Pathway,http://dx.doi.org/10.1128/JVI.02560-09,PMC2897593,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) was identified to be the causative agent of SARS with atypical pneumonia. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for SARS-CoV. It is not clear whether ACE2 conveys signals from the cell surface to the nucleus and regulates expression of cellular genes upon SARS-CoV infection. To understand the pathogenesis of SARS-CoV, human type II pneumocyte (A549) cells were incubated with the viral spike protein or with SARS-CoV virus-like particles containing the viral spike protein to examine cytokine modulation in lung cells. Results from oligonucleotide-based microarray, real-time PCR, and enzyme-linked immunosorbent assays indicated an upregulation of the fibrosis-associated chemokine (C-C motif) ligand 2 (CCL2) by the viral spike protein and the virus-like particles. The upregulation of CCL2 by SARS-CoV spike protein was mainly mediated by extracellular signal-regulated kinase 1 and 2 (ERK1/2) and AP-1 but not the IκBα-NF-κB signaling pathway. In addition, Ras and Raf upstream of the ERK1/2 signaling pathway were involved in the upregulation of CCL2. Furthermore, ACE2 receptor was activated by casein kinase II-mediated phosphorylation in cells pretreated with the virus-like particles containing spike protein. These results indicate that SARS-CoV spike protein triggers ACE2 signaling and activates fibrosis-associated CCL2 expression through the Ras-ERK-AP-1 pathway.",,"['Chen, I-Yin', 'Chang, Shin C.', 'Wu, Hung-Yi', 'Yu, Ting-Chun', 'Wei, Wen-Chin', 'Lin, Shiming', 'Chien, Chung-Liang', 'Chang, Ming-Fu']",,,,
,PMC,CISH and Susceptibility to Infectious Diseases,http://dx.doi.org/10.1056/NEJMoa0905606,PMC3646238,,,"BACKGROUND: The interleukin-2 (IL2)-mediated immune response is critical for host defence against infectious pathogens. CISH, a suppressor of cytokine signalling, controls IL2 signalling. METHODS: We tested for association between CISH polymorphisms and susceptibility to major infectious diseases (bacteremia, tuberculosis and severe malaria) in 8402 persons from the Gambia, Hong Kong, Kenya, Malawi, and Vietnam using a case-control design. We have previously tested twenty other immune-related genes in one or more of these sample collections. RESULTS: We observed associations between variant alleles of multiple CISH polymorphisms and increased susceptibility to each infectious disease in each of the study populations. When all five SNPs (CISH −639, −292, −163, +1320 and +3415) within the CISH-associated locus were considered together in a multi-SNP score, we found substantial support for an effect of CISH genetic variants on susceptibility to bacteremia, malaria, and tuberculosis (overall P=3.8 × 10(−11)) with CISH −292 being “responsible” for the majority of the association signal (P=4.58×10(−7)). Peripheral blood mononuclear cells of adult volunteers carrying the CISH −292 variant showed a muted response to IL2 stimulation — in the form of 25-40% less CISH — when compared with “control” cells lacking the −292 variant. CONCLUSIONS: Variants of CISH are associated with susceptibility to diseases caused by diverse infectious pathogens, suggesting that negative regulators of cytokine signalling may play a major role in immunity against various infectious diseases. The overall risk of having one of these infectious diseases was found to be increased by at least 18 percent in individuals carrying the variant CISH alleles.",,"['Khor, Chiea C.', 'Vannberg, Fredrik O.', 'Chapman, Stephen J.', 'Guo, Haiyan', 'Wong, Sunny H.', 'Walley, Andrew J.', 'Vukcevic, Damjan', 'Rautanen, Anna', 'Mills, Tara C.', 'Chang, Kwok-Chiu', 'Kam, Kai-Man', 'Crampin, Amelia C.', 'Ngwira, Bagrey', 'Leung, Chi-Chiu', 'Tam, Cheuk-Ming', 'Chan, Chiu-Yeung', 'Sung, Joseph J.Y.', 'Yew, Wing-Wai', 'Toh, Kai-Yee', 'Tay, Stacey K.H.', 'Kwiatkowski, Dominic', 'Lienhardt, Christian', 'Hien, Tran-Tinh', 'Day, Nicholas P.', 'Peshu, Nobert', 'Marsh, Kevin', 'Maitland, Kathryn', 'Scott, J. Anthony', 'Williams, Thomas N.', 'Berkley, James A.', 'Floyd, Sian', 'Tang, Nelson L.S.', 'Fine, Paul E.M.', 'Goh, Denise L.M.', 'Hill, Adrian V.S.']",,,,
,PMC,Cellular response to influenza virus infection: a potential role for autophagy in CXCL10 and interferon-alpha induction,http://dx.doi.org/10.1038/cmi.2010.25,PMC4003230,,,"Historically, influenza pandemics have arisen from avian influenza viruses. Avian influenza viruses H5N1 and H9N2 are potential pandemic candidates. Infection of humans with the highly pathogenic avian influenza H5N1 virus is associated with a mortality in excess of 60%, which has been attributed to dysregulation of the cytokine system. Human macrophages and epithelial cells infected with some genotypes of H5N1 and H9N2 viruses express markedly elevated cytokine and chemokine levels when compared with seasonal influenza A subtype H1N1 virus. The mechanisms underlying this cytokine and chemokine hyperinduction are not fully elucidated. In the present study, we demonstrate that autophagy, a tightly regulated homeostatic process for self-digestion of unwanted cellular subcomponents, plays a role in cytokine induction. Autophagy is induced to a greater extent by H9N2/G1, in association with cytokine hyperinduction, compared with H1N1 and the novel pandemic swine-origin influenza A/H1N1 viruses. Using 3-methyladenine to inhibit autophagy and small interfering RNA to silence the autophagy gene, Atg5, we further show that autophagic responses play a role in influenza virus-induced CXCL10 and interferon-α expression in primary human blood macrophages. Our results provide new insights into the pathogenic mechanisms of avian influenza viruses.",,"['Law, Anna Hing-Yee', 'Lee, Davy Chun-Wai', 'Yuen, Kwok-Yung', 'Peiris, Malik', 'Lau, Allan Sik-Yin']",,,,
,PMC,Viral shedding and clinical illness in naturally acquired influenza virus infections,http://dx.doi.org/10.1086/652241,PMC3060408,,,"BACKGROUND: Volunteer challenge studies have provided detailed data on viral shedding from the respiratory tract before and through the course of experimental influenza virus infection. There are no comparable quantitative data on naturally-acquired infections. METHODS: In a community-based study in Hong Kong in 2008, we followed up initially well individuals to quantify trends in viral shedding based on culture and reverse transcription polymerase chain reaction (RT-PCR) through the course of illness associated with seasonal influenza A and B virus infection. RESULTS: Trends in symptom scores more closely matched changes in molecular viral loads measured by RT-PCR for influenza A than influenza B. For influenza A virus infections, replicating viral loads measured by culture declined to undetectable levels earlier after illness onset than molecular viral loads. Most viral shedding occurred during the first 2–3 days after illness onset and we estimated that 1–8% of infectiousness occurs prior to illness onset. Only 14% of infections with detectable shedding by RT-PCR were asymptomatic, and viral shedding was low in these cases. CONCLUSIONS: Our results suggest that ‘silent spreaders’ (i.e. individuals who are infectious while asymptomatic or pre-symptomatic) may be less important in the spread of influenza epidemics than previously thought.",,"['Lau, Lincoln L. H.', 'Cowling, Benjamin J.', 'Fang, Vicky J.', 'Chan, Kwok-Hung', 'Lau, Eric H. Y.', 'Lipsitch, Marc', 'Cheng, Calvin K. Y.', 'Houck, Peter M.', 'Uyeki, Timothy M.', 'Malik Peiris, J. S.', 'Leung, Gabriel M.']",,,,
,PMC,Innate Immunology of Bovine Respiratory Disease,http://dx.doi.org/10.1016/j.cvfa.2010.03.001,PMC2904317,,,,,"['Ackermann, Mark R', 'Derscheid, Rachel', 'Roth, James A']",,,,
,PMC,"Quantitative Proteomics Using Stable Isotope Labeling with Amino Acids in Cell Culture Reveals Changes in the Cytoplasmic, Nuclear, and Nucleolar Proteomes in Vero Cells Infected with the Coronavirus Infectious Bronchitis Virus",http://dx.doi.org/10.1074/mcp.M900345-MCP200,PMC2938107,,,"Virus-host interactions involve complex interplay between viral and host factors, rendering them an ideal target for proteomic analysis. Here we detail a high throughput quantitative proteomics analysis of Vero cells infected with the coronavirus infectious bronchitis virus (IBV), a positive strand RNA virus that replicates in the cytoplasm. Stable isotope labeling with amino acids in cell culture (SILAC) was used in conjunction with LC-MS/MS to identify and quantify 1830 cellular and two viral proteins from IBV-infected cells. Fractionation of cells into cytoplasmic, nuclear, and nucleolar extracts was used to reduce sample complexity and provide information on the trafficking of proteins between the different compartments. Each fraction showed a proportion of proteins exhibiting ≥2-fold changes in abundance. Ingenuity Pathway Analysis revealed that proteins that changed in response to infection could be grouped into different functional categories. These included proteins regulated by NF-κB- and AP-1-dependent pathways and proteins involved in the cytoskeleton and molecular motors. A luciferase-based reporter gene assay was used to validate the up-regulation of AP-1- and NF-κB-dependent transcription in IBV-infected cells and confirmed using immunofluorescence. Immunofluorescence was used to validate changes in the subcellular localization of vimentin and myosin VI in IBV-infected cells. The proteomics analysis also confirmed the presence of the viral nucleocapsid protein as localizing in the cytoplasm, nucleus, and nucleolus and the viral membrane protein in the cytoplasmic fraction. This research is the first application of SILAC to study total host cell proteome changes in response to positive sense RNA virus infection and illustrates the versatility of this technique as applied to infectious disease research.",,"['Emmott, Edward', 'Rodgers, Mark A.', 'Macdonald, Andrew', 'McCrory, Sarah', 'Ajuh, Paul', 'Hiscox, Julian A.']",,,,
,PMC,Maintenance of influenza virus infectivity on the surfaces of personal protective equipment and clothing used in healthcare settings,http://dx.doi.org/10.1007/s12199-010-0149-y,PMC2955907,,,"OBJECTIVES: The maintenance of infectivity of influenza viruses on the surfaces of personal protective equipment and clothing is an important factor in terms of controlling viral cross-infection in the environment and preventing contact infection. The aim of this study was to determine if laboratory-grown influenza A (H1N1) virus maintained infectivity on the surfaces of personal protective equipment and clothing used in healthcare settings. METHODS: Influenza A virus (0.5 mL) was deposited on the surface of a rubber glove, an N95 particulate respirator, a surgical mask made of non-woven fabric, a gown made of Dupont Tyvek, a coated wooden desk, and stainless steel. Each sample was left for 1, 8, and 24 h, and hemagglutination (HA) and 50% tissue culture infective dose (TCID(50))/mL were measured. RESULTS: The HA titer of this influenza A virus did not decrease in any of the materials tested even after 24 h. The infectivity of influenza A virus measured by TCID(50) was maintained for 8 h on the surface of all materials, with the exception of the rubber glove for which virus infectivity was maintained for 24 h. CONCLUSIONS: Our results indicate that the replacement/renewal of personal protective equipment and clothing by healthcare professionals in cases of exposure to secretions and droplets containing viruses spread by patients is an appropriate procedure to prevent cross-infection.",,"['Sakaguchi, Hiroko', 'Wada, Koji', 'Kajioka, Jitsuo', 'Watanabe, Mayumi', 'Nakano, Ryuichi', 'Hirose, Tatsuko', 'Ohta, Hiroshi', 'Aizawa, Yoshiharu']",,,,
,PMC,Bat Guano Virome: Predominance of Dietary Viruses from Insects and Plants plus Novel Mammalian Viruses,http://dx.doi.org/10.1128/JVI.00501-10,PMC2898246,,,"Bats are hosts to a variety of viruses capable of zoonotic transmissions. Because of increased contact between bats, humans, and other animal species, the possibility exists for further cross-species transmissions and ensuing disease outbreaks. We describe here full and partial viral genomes identified using metagenomics in the guano of bats from California and Texas. A total of 34% and 58% of 390,000 sequence reads from bat guano in California and Texas, respectively, were related to eukaryotic viruses, and the largest proportion of those infect insects, reflecting the diet of these insectivorous bats, including members of the viral families Dicistroviridae, Iflaviridae, Tetraviridae, and Nodaviridae and the subfamily Densovirinae. The second largest proportion of virus-related sequences infects plants and fungi, likely reflecting the diet of ingested insects, including members of the viral families Luteoviridae, Secoviridae, Tymoviridae, and Partitiviridae and the genus Sobemovirus. Bat guano viruses related to those infecting mammals comprised the third largest group, including members of the viral families Parvoviridae, Circoviridae, Picornaviridae, Adenoviridae, Poxviridae, Astroviridae, and Coronaviridae. No close relative of known human viral pathogens was identified in these bat populations. Phylogenetic analysis was used to clarify the relationship to known viral taxa of novel sequences detected in bat guano samples, showing that some guano viral sequences fall outside existing taxonomic groups. This initial characterization of the bat guano virome, the first metagenomic analysis of viruses in wild mammals using second-generation sequencing, therefore showed the presence of previously unidentified viral species, genera, and possibly families. Viral metagenomics is a useful tool for genetically characterizing viruses present in animals with the known capability of direct or indirect viral zoonosis to humans.",,"['Li, Linlin', 'Victoria, Joseph G.', 'Wang, Chunlin', 'Jones, Morris', 'Fellers, Gary M.', 'Kunz, Thomas H.', 'Delwart, Eric']",,,,
,PMC,Pepscan Mapping of Viral Hemorrhagic Septicemia Virus Glycoprotein G Major Lineal Determinants Implicated in Triggering Host Cell Antiviral Responses Mediated by Type I Interferon,http://dx.doi.org/10.1128/JVI.00023-10,PMC2898232,,,"Surface glycoproteins of enveloped virus are potent elicitors of type I interferon (IFN)-mediated antiviral responses in a way that may be independent of the well-studied genome-mediated route. However, the viral glycoprotein determinants responsible for initiating the IFN response remain unidentified. In this study, we have used a collection of 60 synthetic 20-mer overlapping peptides (pepscan) spanning the full length of glycoprotein G (gpG) of viral hemorrhagic septicemia virus (VHSV) to investigate what regions of this protein are implicated in triggering the type I IFN-associated immune responses. Briefly, two regions with ability to increase severalfold the basal expression level of the IFN-stimulated mx gene and to restrict the spread of virus among responder cells were mapped to amino acid residues 280 to 310 and 340 to 370 of the gpG protein of VHSV. In addition, the results obtained suggest that an interaction between VHSV gpG and integrins might trigger the host IFN-mediated antiviral response after VHSV infection. Since it is known that type I IFN plays an important role in determining/modulating the protective-antigen-specific immune responses, the identification of viral glycoprotein determinants directly implicated in the type I IFN induction might be of special interest for designing new adjuvants and/or more-efficient and cost-effective viral vaccines as well as for improving our knowledge on how to stimulate the innate immune system.",,"['Chico, V.', 'Martinez-Lopez, A.', 'Ortega-Villaizan, M.', 'Falco, A.', 'Perez, L.', 'Coll, J. M.', 'Estepa, A.']",,,,
,PMC,Correction: In Vitro Reconstitution of SARS-Coronavirus mRNA Cap Methylation,http://dx.doi.org/10.1371/annotation/a0dde376-2eb1-4ce3-8887-d29f5ba6f162,PMC2869341,,CC BY,,2010 May 12,"['Bouvet, Mickaël', 'Debarnot, Claire', 'Imbert, Isabelle', 'Selisko, Barbara', 'Snijder, Eric J.', 'Canard, Bruno', 'Decroly, Etienne']",PLoS Pathog,,,
,PMC,Isopeptidases in anticancer therapy: looking for inhibitors,,PMC2892408,,,"Addition of polypeptides belonging to the ubiquitin family to selected lysines residues is a widespread post-translation modification (PTM) that controls many fundamental aspects of cell's life. Specific alterations in the normal turnover of this PTM are frequently observed in tumors. The conjugation/deconjugation cycle of ubiquitin (Ub) or ubiquitin-like (Ubl) proteins influences the activities of oncogenes and tumor suppressor genes. Two families of enzymes work in antagonizing manner to add or remove Ub and Ubl-proteins on target proteins: the E3 ligases and the isopeptidases. These enzymes are the subjects of fervent research with the ambition to comprehend their regulation, their mechanisms of action, their involvement in human diseases, and to develop specific inhibitors for therapeutic intervention. Here we will discuss of isopeptidases, the deconjugating enzymes, with particular emphasis on the proapoptotic activities of the relative inhibitors identified so far.",,"['Sgorbissa, Andrea', 'Potu, Harish', 'Brancolini, Claudio']",,,,
,PMC,Characterization of the Gene Expression Profile of Human Bocavirus,http://dx.doi.org/10.1016/j.virol.2010.04.014,PMC2879452,,,"We have generated a quantitative transcription profile of human bocavirus type 1 (HBoV1) by transfecting a nearly full-length clone in human lung epithelial A549 cells as well as in a replication competent system in 293 cells. The overall transcription profile of HBoV1 is similar to that of two other members of genus Bocavirus, minute virus of canines and bovine parvovirus 1. In particular, a spliced NS1-transcript that was not recognized previously expressed the large non-structural protein NS1 at approximately 100 kDa; and the NP1-encoding transcripts were expressed abundantly. In addition, the protein expression profile of human bocavirus type 2 (HBoV2) was examined in parallel by transfection of a nearly full-length clone in A549 cells, which is similar to that of HBoV1. Moreover, our results showed that, unlike human parvovirus B19 infection, expression of the HBoV1 proteins only does not induce cell cycle arrest and apoptosis of A549 cells.",,"['Chen, Aaron Yun', 'Cheng, Fang', 'Lou, Sai', 'Luo, Yong', 'Liu, Zhengwen', 'Delwart, Eric', 'Pintel, David', 'Qiu, Jianming']",,,,
,PMC,Inhibition of Heat-Shock Protein 90 Reduces Ebola Virus Replication,http://dx.doi.org/10.1016/j.antiviral.2010.04.015,PMC2907434,,,"Ebola virus (EBOV), a negative-sense RNA virus in the family Filoviridae, is known to cause severe hemorrhagic fever in humans and other primates. Infection with EBOV causes a high mortality rate and currently there is no FDA-licensed vaccine or therapeutic treatment available. Recently, heat-shock protein 90 (Hsp90), a molecular chaperone, was shown to be an important host factor for the replication of several negative-strand viruses. We tested the effect of several different Hsp90 inhibitors including geldanamycin, radicicol, and 17-allylamino-17-demethoxygeldanamycin (17-AAG; a geldanamycin analog) on the replication of Zaire EBOV. Our results showed that inhibition of Hsp90 significantly reduced the replication of EBOV. Classic Hsp90 inhibitors reduced viral replication with an effective concentration at 50% (EC(50)) in the high nanomolar to low micromolar range, while drugs from a new class of Hsp90 inhibitors showed markedly more potent inhibition. These compounds blocked EBOV replication with an EC(50) in the low nanomolar range and showed significant potency in blocking replication in primary human monocytes. These results validated that Hsp90 is an important host factor for the replication of filoviruses and suggest that Hsp90 inhibitors may be therapeutically effective in treating EBOV infection.",,"['Smith, Darci R.', 'McCarthy, Sarah', 'Chrovian, Andrew', 'Olinger, Gene', 'Stossel, Andrea', 'Geisbert, Thomas W.', 'Hensley, Lisa E.', 'Connor, John H.']",,,,
,PMC,"Multi-talented DEAD-box proteins and potential tumor promoters: p68 RNA helicase (DDX5) and its paralog, p72 RNA helicase (DDX17)",,PMC2892403,,,"P68 (DDX5) and p72 (DDX17) are members of the DEAD-box RNA helicase family. They can unwind double-stranded RNA and also contribute to the remodeling of ribonucleoprotein complexes. These activities of p68/p72 are required for efficient RNA splicing and microRNA processing. In addition, p68/p72 perform functions that are independent of their enzymatic activity. This is especially common to their role in gene regulation, where p68/p72 coactivate various transcription factors, including the tumor suppressor p53, estrogen receptor α and β-catenin. P68/p72 are posttranslationally modified by SUMO attachment and phosphorylation that regulate their coactivation potential, binding to known interactants or protein stability. Knock-out mouse models revealed that both DDX5 and DDX17 are essential genes during development. Furthermore, together with their ability to stimulate cell proliferation and prevent apoptosis, the reported overexpression of p68/p72 in three of the major human cancers (colon, breast, prostate) strongly suggests that p68/p72 promote tumorigenesis and might even represent proto-oncoproteins. If so, their inhibition holds promise as a novel way to contain or cure various carcinomas",,"Janknecht, Ralf",,,,
,PMC,Functional and Genetic Studies of the Substrate Specificity of Coronavirus Infectious Bronchitis Virus 3C-Like Proteinase,http://dx.doi.org/10.1128/JVI.02490-09,PMC2898227,,,"Coronavirus (CoV) 3C-like proteinase (3CLpro), located in nonstructural protein 5 (nsp5), processes the replicase polyproteins 1a and 1ab (pp1a and pp1ab) at 11 specific sites to produce 12 mature nonstructural proteins (nsp5 to nsp16). Structural and biochemical studies suggest that a conserved Gln residue at the P1 position is absolutely required for efficient cleavage. Here, we investigate the effects of amino acid substitution at the P1 position of 3CLpro cleavage sites of infectious bronchitis virus (IBV) on the cleavage efficiency and viral replication by in vitro cleavage assays and reverse genetic approaches. Our results demonstrated that a P1-Asn substitution at the nsp4-5/Q2779, nsp5-6/Q3086, nsp7-8/Q3462, nsp8-9/Q3672, and nsp9-10/Q3783 sites, a P1-Glu substitution at the nsp8-9/Q3672 site, and a P1-His substitution at the nsp15-16/Q6327 site were tolerated and allowed recovery of infectious mutant viruses, albeit with variable degrees of growth defects. In contrast, a P1-Asn substitution at the nsp6-7/Q3379, nsp12-13/Q4868, nsp13-14/Q5468, and nsp14-15/Q5989 sites, as well as a P1-Pro substitution at the nsp15-16/Q6327 site, abolished 3CLpro-mediated cleavage at the corresponding position and blocked the recovery of infectious viruses. Analysis of the effects of these lethal mutations on RNA synthesis suggested that processing intermediates, such as the nsp6-7, nsp12-13, nsp13-14, nsp14-15, and nsp15-16 precursors, may function in negative-stranded genomic RNA replication, whereas mature proteins may be required for subgenomic RNA (sgRNA) transcription. More interestingly, a mutant 3CLpro with either a P166S or P166L mutation was selected when an IBV infectious cDNA clone carrying the Q6327N mutation at the nsp15-16 site was introduced into cells. Either of the two mutations was proved to enhance significantly the 3CLpro-mediated cleavage efficiency at the nsp15-16 site with a P1-Asn substitution and compensate for the detrimental effects on recovery of infectious virus.",,"['Fang, Shouguo', 'Shen, Hongyuan', 'Wang, Jibin', 'Tay, Felicia P. L.', 'Liu, Ding Xiang']",,,,
,PMC,Ecological factors driving the long-term evolution of influenza's host range,http://dx.doi.org/10.1098/rspb.2010.0519,PMC2981989,,,"The evolution of a pathogen's host range is shaped by the ecology of its hosts and by the physiological traits that determine host specificity. For many pathogen traits, there is a trade-off: a phenotype suitable for infecting one set of hosts poorly infects another. Introducing and analysing a simple evo-epidemiological model, here we study how such a trade-off is expected to affect evolution of the host ranges of influenza viruses. We examine a quantitative trait underlying host specificity, given by an influenza virus's degree of adaptation to certain conformations of sialic acid receptors, and investigate how this receptor preference evolves in a minimal network of host species, including humans, that differ in life history and receptor physiology. Using adaptive dynamics theory, we establish thresholds in interspecific transmission rates and host population sizes that govern the emergence and persistence of human-adapted viruses. These ecological thresholds turn out to be largely independent of the strength of the evolutionary trade-off, underscoring the importance of ecological conditions in determining a disease's host range.",,"['Cobey, Sarah', 'Pascual, Mercedes', 'Dieckmann, Ulf']",,,,
,PMC,Trafficking of immune cells in the central nervous system,http://dx.doi.org/10.1172/JCI41911,PMC2860945,,,"The CNS is an immune-privileged environment, yet the local control of multiple pathogens is dependent on the ability of immune cells to access and operate within this site. However, inflammation of the distinct anatomical sites (i.e., meninges, cerebrospinal fluid, and parenchyma) associated with the CNS can also be deleterious. Therefore, control of lymphocyte entry and migration within the brain is vital to regulate protective and pathological responses. In this review, several recent advances are highlighted that provide new insights into the processes that regulate leukocyte access to, and movement within, the brain.",,"['Wilson, Emma H.', 'Weninger, Wolfgang', 'Hunter, Christopher A.']",,,,
,PMC,"CCR5 Signaling Suppresses Inflammation and Reduces Adverse Remodeling of the Infarcted Heart, Mediating Recruitment of Regulatory T Cells",http://dx.doi.org/10.2353/ajpath.2010.090759,PMC2861083,,,"Myocardial infarction triggers an inflammatory reaction that is involved in cardiac remodeling. Cardiac repair is dependent on regulatory mechanisms that suppress inflammation and prevent excessive matrix degradation. Chemokine induction in the infarcted heart mediates recruitment of leukocyte subsets with distinct properties. We demonstrate that signaling through the CC chemokine receptor 5 (CCR5) prevents uncontrolled postinfarction inflammation and protects from adverse remodeling by recruiting suppressive mononuclear cells. CCR5 and its ligands macrophage inflammatory protein (MIP)−1α and MIP-1β were markedly induced in the infarcted mouse myocardium. In addition, almost 40% of the mononuclear cells infiltrating the infarct expressed CCR5. CCR5(−/−) mice exhibited marked upregulation of proinflammatory cytokine and chemokine expression in the infarct. In wild-type infarcts CCR5(+) mononuclear cells had anti-inflammatory properties, expressing higher levels of IL-10 than CCR5(−) cells. In contrast, mononuclear cells isolated from CCR5(−/−) infarcts had reduced IL-10 expression. Moreover, enhanced inflammation in the absence of CCR5 was associated with impaired recruitment of CD4(+)/foxp3(+) regulatory T cells (Tregs). The CCR5(+) Treg subset exhibited increased IL-10 expression, reflecting potent anti-inflammatory activity. Accentuated inflammation in CCR5(−/−) infarcts was associated with increased matrix metalloproteinase (MMP) expression, reduced TIMP levels, and enhanced MMP-2 and MMP-9 activity, resulting in worse cardiac dilation. These results suggest that CCR5-mediated Treg recruitment may restrain postinfarction inflammation, preventing excessive matrix degradation and attenuating adverse remodeling.",,"['Dobaczewski, Marcin', 'Xia, Ying', 'Bujak, Marcin', 'Gonzalez-Quesada, Carlos', 'Frangogiannis, Nikolaos G.']",,,,
,PMC,"Clinical and Laboratory Features That Differentiate Dengue from Other Febrile Illnesses in an Endemic Area—Puerto Rico, 2007–2008",http://dx.doi.org/10.4269/ajtmh.2010.09-0552,PMC2861403,,,"Dengue infection can be challenging to diagnose early in the course of infection before severe manifestations develop, but early diagnosis can improve patient outcomes and promote timely public health interventions. We developed age-based predictive models generated from 2 years of data from an enhanced dengue surveillance system in Puerto Rico. These models were internally validated and were able to differentiate dengue infection from other acute febrile illnesses with moderate accuracy. The accuracy of the models was greater than either the current World Health Organization case definition for dengue fever or a proposed modification to this definition, while requiring the collection of fewer data. In young children, thrombocytopenia and the absence of cough were associated with dengue infection; for adults, rash, leucopenia, and the absence of sore throat were associated with dengue infection; in all age groups, retro-orbital pain was associated with dengue infection.",,"['Gregory, Christopher J.', 'Santiago, Luis Manuel', 'Argüello, D. Fermin', 'Hunsperger, Elizabeth', 'Tomashek, Kay M.']",,,,
,PMC,Identification of Adenoviruses in Fecal Specimens from Wild Chimpanzees (Pan trogylodytes schweinfurthii) in Western Tanzania,http://dx.doi.org/10.4269/ajtmh.2010.09-0668,PMC2861384,,,"DNA of two distinctive adenoviruses was detected in wild chimpanzees in western Tanzania that showed clinical signs of acute, upper respiratory disease, notably coughing. The amplified sequences from part of the capsid hexon gene suggests that one virus is a novel adenovirus serotype candidate and the other virus is a species C adenovirus most closely related to recent isolates from captive chimpanzees in the United States, Simian AdV 37 with 86% nucleic acid identity and Simian AdV 40 with 95% nucleic acid identity, respectively. The species C adenovirus sequences suggest possible recombination with a human adenovirus. The source of these viruses and disease association is not known.",,"['Tong, Suxiang', 'Singh, Jatinder', 'Ruone, Susan', 'Humphrey, Charles', 'Yip, Cyril C. Y.', 'Lau, Susanna K. P.', 'Anderson, Larry J.', 'Kaur, Taranjit']",,,,
,PMC,Ecology of avian influenza viruses in a changing world,http://dx.doi.org/10.1111/j.1749-6632.2010.05451.x,PMC2981064,,,"Influenza A virus infections result in ~500,000 human deaths per year and many more sub-lethal infections. Wild birds are recognized as the ancestral host of influenza A viruses, and avian viruses have contributed genetic material to most human viruses, including subtypes H5N1 and H1N1. Thus, influenza virus transmission in wild and domestic animals and humans is intimately connected. Here we review how anthropogenic change, including human population growth, land use, climate change, globalization of trade, agricultural intensification, and changes in vaccine technology may alter the evolution and transmission of influenza viruses. Evidence suggests that viral transmission in domestic poultry, spillover to other domestic animals, wild birds and humans, and the potential for subsequent pandemic spread, are all increasing. We highlight four areas in need of research: drivers of viral subtype dynamics; ecological and evolutionary determinants of transmissibility and virulence in birds and humans; the impact of changing land use and climate on hosts, viruses, and transmission; and the impact of influenza viruses on wild bird hosts, including their ability to migrate while shedding virus.",,"['Vandegrift, Kurt J.', 'Sokolow, Susanne H.', 'Daszak, Peter', 'Kilpatrick, A. Marm']",,,,
,PMC,Quiz Corner,,PMC2857422,,,,,,,,,
,PMC,ANTIVIRAL COMPOUNDS IN THE PIPELINE TO TACKLE H1N1 INFLUENZA INFECTION,http://dx.doi.org/10.1358/dof.2010.035.05.1487081,PMC3129656,,,"The recent pandemic of H1N1 has demonstrated the potential vulnerability of the human population to novel influenza viruses. While there is recent increased interest and effort in developing effective anti-influenza agents, few new products have entered clinical studies. This review will highlight the limited armamentarium of licensed influenza agents, and discuss novel compounds and strategies that have entered clinical studies and may therefore be imminently available to the treating clinician.",,"Beigel, J.H.",,,,
,PMC,HETEROLOGOUS IMMUNITY BETWEEN VIRUSES,http://dx.doi.org/10.1111/j.0105-2896.2010.00897.x,PMC2917921,,,"Immune memory responses to previously encountered pathogens can sometimes alter the immune response to and the course of infection of an unrelated pathogen by a process known as heterologous immunity. This response can lead to enhanced or diminished protective immunity and altered immunopathology. Here we discuss the nature of T-cell cross-reactivity and describe matrices of epitopes from different viruses eliciting cross-reactive CD8(+) T-cell responses. We examine the parameters of heterologous immunity mediated by these cross-reactive T cells during viral infections in mice and humans. We show that heterologous immunity can disrupt T-cell memory pools, alter the complexity of the T-cell repertoire, change patterns of T-cell immunodominance, lead to the selection of viral epitope-escape variants, alter the pathogenesis of viral infections, and, by virtue of the private specificity of T-cell repertoires within individuals, contribute to dramatic variations in viral disease. We propose that heterologous immunity is an important factor in resistance to and variations of human viral infections and that issues of heterologous immunity should be considered in the design of vaccines.",,"['Welsh, Raymond M.', 'Che, Jenny', 'Brehm, Michael A.', 'Selin, Liisa K.']",,,,
,PMC,"Respiratory Virus Pneumonia after Hematopoietic Cell Transplantation: Associations Between Viral Load in Bronchoalveolar Lavage, Viral RNA Detection in Serum, and Transplant Outcomes",http://dx.doi.org/10.1086/651662,PMC2853730,,,"BACKGROUND: Few data exist regarding respiratory virus quantitation in lower respiratory samples and detection in serum from hematopoietic cell transplantation (HCT) recipients with respiratory virus-associated pneumonia. METHODS: We retrospectively identified HCT recipients with respiratory syncytial virus (RSV), parainfluenza (PIV), influenza, metapneumovirus (MPV), and coronavirus (CoV) detected in BAL samples, and tested stored BAL and/or serum samples using quantitative PCR. RESULTS: In 85 BAL samples from 82 patients, median viral load in copies/ml for RSV (n=35) was 2.6×10(6), PIV (n=35) 4.9×10(7), influenza (n=9) 6.8×10(5), MPV (n=7) 3.9×10(7), and CoV (n=4) 1.8×10(5). Quantitative viral load was not associated with mechanical ventilation or death. Viral RNA was detected in serum of 6 of 66 patients: 4 of 41 with RSV pneumonia, 1 with influenza B, and 1 with MPV/influenza A/CoV co-infection (influenza A and MPV RNA detected). RSV detection in serum was associated with high viral load in BAL (p=0.05). Detection of viral RNA in serum was significantly associated with death (adjusted RR 1.8, p=0.02). CONCLUSION: Quantitative PCR detects high viral load in BAL samples from HCT recipients with respiratory virus pneumonia. Viral RNA is also detectable in serum of patients with RSV, influenza, and MPV pneumonia, and may correlate with disease severity.",,"['Campbell, Angela P.', 'Chien, Jason W.', 'Kuypers, Jane', 'Englund, Janet A.', 'Wald, Anna', 'Guthrie, Katherine A.', 'Corey, Lawrence', 'Boeckh, Michael']",,,,
,PMC,Simulating School Closure Strategies to Mitigate an Influenza Epidemic,http://dx.doi.org/10.1097/PHH.0b013e3181ce594e,PMC2901099,,,"BACKGROUND: There remains substantial debate over the impact of school closure as a mitigation strategy during an influenza pandemic. The ongoing 2009 H1N1 influenza pandemic has provided an unparalleled opportunity to test interventions with the most up-to-date simulations. METHODS: To assist the Allegheny County Health Department during the 2009 H1N1 influenza pandemic, the University of Pittsburgh Models of Infectious Disease Agents Study group employed an agent-based computer simulation model (ABM) of Allegheny County, Pennsylvania, to explore the effects of various school closure strategies on mitigating influenza epidemics of different reproductive rates (R(0)). RESULTS: Entire school system closures were not more effective than individual school closures. Any type of school closure may need to be maintained throughout most of the epidemic (ie, at least 8 weeks) to have any significant effect on the overall serologic attack rate. In fact, relatively short school closures (ie, 2 weeks or less) may actually slightly increase the overall attack rate by returning susceptible students back into schools in the middle of the epidemic. Varying the illness threshold at which school closures are triggered did not seem to have substantial impact on the effectiveness of school closures, suggesting that short delays in closing schools should not cause concern. CONCLUSIONS: School closures alone may not be able to quell an epidemic but, when maintained for at least 8 weeks, could delay the epidemic peak for up to a week, providing additional time to implement a second more effective intervention such as vaccination.",,"['Lee, Bruce Y.', 'Brown, Shawn T.', 'Cooley, Philip', 'Potter, Maggie A.', 'Wheaton, William D.', 'Voorhees, Ronald E.', 'Stebbins, Samuel', 'Grefenstette, John J.', 'Zimmer, Shanta M.', 'Zimmerman, Richard', 'Assi, Tina-Marie', 'Bailey, Rachel R.', 'Wagener, Diane K.', 'Burke, Donald S.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00528-10,PMC2863774,,,,,,,,,
,PMC,"Therapeutic antibodies, vaccines and antibodyomes",,PMC2881260,,,"The potential for antibodies to act as “magic bullets” for treatment of human disease was recognized a century ago, but its full realization has began to occur only during the last decade. A key to their current success is the ability to make libraries of antibodies/B cells, isolate a single species, and engineer it to be safe, efficacious and of high quality. Despite this progress, major challenges to the effective prevention, diagnosis and treatment of a vast majority of diseases remain. Limited success in the development of effective vaccines against diseases such as AIDS and cancer reflects our incomplete understanding of how antibodies are generated and function. Only a miniscule number of antibodies are characterized out of the universe of antibodies generated by the immune system. Knowledge of antibodyomes—the complete sets of antibodies—could help solve these and other challenges.",,"Dimitrov, Dimiter S",,,,
,PMC,Synthetic Biology: Applications Come of Age,http://dx.doi.org/10.1038/nrg2775,PMC2896386,,,"Synthetic biology is bringing together engineers and biologists to design and build novel biomolecular components, networks and pathways, and to use these constructs to rewire and reprogram organisms. These re-engineered organisms will change our lives in the coming years, leading to cheaper drugs, “green” means to fuel our cars, and targeted therapies to attack “superbugs” and diseases such as cancer. The de novo engineering of genetic circuits, biological modules, and synthetic pathways is beginning to address these critical problems and is being used in related practical applications.",,"['Khalil, Ahmad S.', 'Collins, James J.']",,,,
,PMC,Avian influenza pandemic preparedness: developing prepandemic and pandemic vaccines against a moving target,http://dx.doi.org/10.1017/S1462399410001432,PMC2904949,,,"The unprecedented global spread of highly pathogenic avian H5N1 influenza viruses within the past ten years and their extreme lethality to poultry and humans has underscored their potential to cause an influenza pandemic. Combating the threat of an impending H5N1 influenza pandemic will require a combination of pharmaceutical and nonpharmaceutical intervention strategies. The emergence of the H1N1 pandemic in 2009 emphasised the unpredictable nature of a pandemic influenza. Undoubtedly, vaccines offer the most viable means to combat a pandemic threat. Current egg-based influenza vaccine manufacturing strategies are unlikely to be able to cater to the huge, rapid global demand because of the anticipated scarcity of embryonated eggs in an avian influenza pandemic and other factors associated with the vaccine production process. Therefore, alternative, egg-independent vaccine manufacturing strategies should be evaluated to supplement the traditional egg-derived influenza vaccine manufacturing. Furthermore, evaluation of dose-sparing strategies that offer protection with a reduced antigen dose will be critical for pandemic influenza preparedness. Development of new antiviral therapeutics and other, nonpharmaceutical intervention strategies will further supplement pandemic preparedness. This review highlights the current status of egg-dependent and egg-independent strategies against an avian influenza pandemic.",,"['Singh, Neetu', 'Pandey, Aseem', 'Mittal, Suresh K.']",,,,
,PMC,CD13 is dispensable for normal hematopoiesis and myeloid cell functions in the mouse,http://dx.doi.org/10.1189/jlb.0210065,PMC2908940,,,"The robust and consistent expression of the CD13 cell surface marker on very early as well as differentiated myeloid hematopoietic cells has prompted numerous investigations seeking to define roles for CD13 in myeloid cells. To address the function of myeloid CD13 directly, we created a CD13 null mouse and assessed the responses of purified primary macrophages or DCs from WT and CD13 null animals in cell assays and inflammatory disease models, where CD13 has been implicated previously. We find that mice lacking CD13 develop normally with normal hematopoietic profiles except for an increase in thymic but not peripheral T cell numbers. Moreover, in in vitro assays, CD13 appears to be largely dispensable for the aspects of phagocytosis, proliferation, and antigen presentation that we tested, although we observed a slight decrease in actin-independent erythrocyte uptake. However, in agreement with our published studies, we show that lack of monocytic CD13 completely ablates anti-CD13-dependent monocyte adhesion to WT endothelial cells. In vivo assessment of four inflammatory disease models showed that lack of CD13 has little effect on disease onset or progression. Nominal alterations in gene expression levels between CD13 WT and null macrophages argue against compensatory mechanisms. Therefore, although CD13 is highly expressed on myeloid cells and is a reliable marker of the myeloid lineage of normal and leukemic cells, it is not a critical regulator of hematopoietic development, hemostasis, or myeloid cell function.",,"['Winnicka, Beata', ""O'Conor, Catherine"", 'Schacke, Wolfgang', 'Vernier, Kaitlyn', 'Grant, Christina L.', 'Fenteany, Fiona Hall', 'Pereira, Flavia E.', 'Liang, Brannen', 'Kaur, Anupinder', 'Zhao, Ran', 'Montrose, David C.', 'Rosenberg, Daniel W.', 'Aguila, Hector L.', 'Shapiro, Linda H.']",,,,
,PMC,Emerging diseases in Chiroptera: why bats?,http://dx.doi.org/10.1098/rsbl.2010.0267,PMC2942877,,,"A conference entitled ‘2nd International Berlin Bat Meeting: Bat Biology and Infectious Diseases’ was held between the 19 and 21 of February 2010 in Berlin, Germany. Researchers from two major disciplines, bat biologists and disease specialists, met for the first time in an interdisciplinary event to share their knowledge about bat-associated diseases. The focus of the meeting was to understand why in particular bats are the hosts of so many of the most virulent diseases globally. During several sessions, key note speakers and participants discussed infectious diseases associated with bats, including viral diseases caused by Henipa-, Filo-, Corona- and Lyssaviruses, the spread of white-nose syndrome in North American bats, bat immunology/immunogenetics, bat parasites, and finally, conservation and human health issues.",,"['Wibbelt, Gudrun', 'Moore, Marianne S.', 'Schountz, Tony', 'Voigt, Christian C.']",,,,
,PMC,Murine Coronavirus Induces Type I Interferon in Oligodendrocytes through Recognition by RIG-I and MDA5,http://dx.doi.org/10.1128/JVI.00016-10,PMC2903279,,,"The murine coronavirus mouse hepatitis virus (MHV) induced the expression of type I interferon (alpha/beta interferon [IFN-α/β]) in mouse oligodendrocytic N20.1 cells. This induction is completely dependent on virus replication, since infection with UV light-inactivated virus could no longer induce IFN-α/β. We show that MHV infection activated both transcription factors, the IFN regulatory factor 3 (IRF-3) and nuclear factor κB (NF-κB), as evidenced by phosphorylation and nuclear translocation of IRF-3 and an increased promoter binding activity for IRF-3 and NF-κB. Furthermore, the cytoplasmic pattern recognition receptor retinoic acid-inducible gene I (RIG-I) was induced by MHV infection. Knockdown of RIG-I by small interfering RNAs blocked the activation of IRF-3 and subsequent IFN-α/β production induced by MHV infection. Knockdown of another cytoplasmic receptor, the melanoma-differentiation-associated gene 5 (MDA5), by small interfering RNAs also blocked IFN-β induction. These results demonstrate that MHV is recognized by both RIG-I and MDA5 and induces IFN-α/β through the activation of the IRF-3 signaling pathway. However, knockdown of RIG-I only partially blocked NF-κB activity induced by MHV infection and inhibition of NF-κB activity by a decoy peptide inhibitor had little effect on IFN-α/β production. These data suggest that activation of the NF-κB pathway might not play a critical role in IFN-α/β induction by MHV infection in oligodendrocytes.",,"['Li, Jianfeng', 'Liu, Yin', 'Zhang, Xuming']",,,,
,PMC,Exchange of the Coronavirus Replicase Polyprotein Cleavage Sites Alters Protease Specificity and Processing,http://dx.doi.org/10.1128/JVI.00752-10,PMC2903247,,,"Coronavirus nonstructural proteins 1 to 3 are processed by one or two papain-like proteases (PLP1 and PLP2) at specific cleavage sites (CS1 to -3). Murine hepatitis virus (MHV) PLP2 and orthologs recognize and cleave at a position following a p4-Leu-X-Gly-Gly-p1 tetrapeptide, but it is unknown whether these residues are sufficient to result in processing by PLP2 at sites normally cleaved by PLP1. We demonstrate that exchange of CS1 and/or CS2 with the CS3 p4-p1 amino acids in engineered MHV mutants switches specificity from PLP1 to PLP2 at CS2, but not at CS1, and results in altered protein processing and virus replication. Thus, the p4-p1 residues are necessary for PLP2 processing but require a specific protein or cleavage site context for optimal PLP recognition and cleavage.",,"['Gadlage, Mark J.', 'Denison, Mark R.']",,,,
,PMC,Use of Plasma Procalcitonin Levels as an Adjunct to Clinical Microbiology,http://dx.doi.org/10.1128/JCM.00655-10,PMC2897488,,,"Procalcitonin (PCT) is synthesized by a large number of tissues and organs in response to invasion by pathogenic bacteria, fungi, and some parasites. Current PCT assays are rapid, specific, and of sufficient sensitivity to detect increases in PCT serum levels within 4 to 6 h of initiation of infection. Clinically, PCT levels may help in decisions regarding the need for empirical antibiotic therapy, “source control” of infection, and duration of antibiotic therapy. The addition of PCT levels to bacterial culture and viral detection results can assist with the separation of colonization and invasion by pathogenic bacteria.",,"Gilbert, David N.",,,,
,PMC,Activation of Egr-1 expression in astrocytes by HIV-1 Tat: new insights into astrocyte-mediated Tat neurotoxicity,http://dx.doi.org/10.1007/s11481-010-9217-8,PMC3056338,,,"Human immunodeficiency virus type 1 (HIV-1) Tat plays an important role in HIV-associated neuropathogenesis; the underlying mechanisms are still evolving. We have recently shown that HIV-1 Tat induces expression of glial fibrillary acidic protein (GFAP), a characteristic of HIV-1 infection of the central nervous system (CNS). We have also shown that the Tat-induced GFAP expression in astrocytes is regulated by p300, and that deletion of the early growth response 1 (Egr-1) cis-transacting element within the p300 promoter abolishes Tat-induced GFAP expression. In this study, we further examined the relationship between Tat and Egr-1 in astrocytes. We found increased Egr-1 protein expression in Tat-expressing human astrocytoma cells and mouse primary astrocytes. Using the Egr-1 promoter-driven firefly luciferase reporter gene assay and the site-directed mutagenesis, we demonstrated that Tat increased Egr-1 expression by transactivating the Egr-1 promoter and involving specific serum response elements (SRE) within the promoter. Consistent with these data, we showed that Tat transactivation of the Egr-1 promoter was abrogated when astrocytes were cultured in serum-reduced media. Taken together, these results reveal that Tat directly transactivates Egr-1 expression and suggest that Tat interaction with Egr-1 is probably one of the very upstream molecular events that initiate Tat-induced astrocyte dysfunction and subsequent Tat neurotoxicity.",,"['Fan, Yan', 'Zou, Wei', 'Green, Linden A.', 'Kim, Byung oh', 'He, Johnny J.']",,,,
,PMC,Host-Encoded Reporters for the Detection and Purification of Multiple Enveloped Viruses,http://dx.doi.org/10.1016/j.jviromet.2010.04.002,PMC2916077,,,"The identification of host cell factors for virus replication holds great promise for the development of new anti-viral therapies. Recently, high-throughput screening methods have emerged as powerful tools to identify candidate host factors for therapeutic intervention. The development of assay systems suitable for large-scale automated screening is of particular importance for novel viruses with high pathogenic potential for which limited biological information can be developed in a short period of time. This report presents a general enzymatic reporter system for the detection and characterization of multiple enveloped viruses that does not rely on engineering of the virus. Instead, reporter enzymes are incorporated into virus particles by targeting to lipid microdomains in producer cells. The approach allows a variety of human pathogenic enveloped viruses to be detected by sensitive, inexpensive and automatable enzymatic assays. Tagged viruses can be purified quickly and efficiently by a magnetic bead-based capture method. The method allows general detection of enveloped viruses without prior reference to their sequence.",,"['Ketteler, Robin', 'Tomov, Vesko', 'Neunkirchner, Alina', 'Xie, Qiang', 'Pickl, Winfried F.', 'Seed, Brian']",,,,
,PMC,"Biocrystallography: past, present, future",http://dx.doi.org/10.2976/1.3369281,PMC2929629,,,"The evolution of biocrystallography from the pioneers’ time to the present era of global biology is presented in relation to the development of methodological and instrumental advances for molecular sample preparation and structure elucidation over the last 6 decades. The interdisciplinarity of the field that generated cross-fertilization between physics- and biology-focused themes is emphasized. In particular, strategies to circumvent the main bottlenecks of biocrystallography are discussed. They concern (i) the way macromolecular targets are selected, designed, and characterized, (ii) crystallogenesis and how to deal with physical and biological parameters that impact crystallization for growing and optimizing crystals, and (iii) the methods for crystal analysis and 3D structure determination. Milestones that have marked the history of biocrystallography illustrate the discussion. Finally, the future of the field is envisaged. Wide gaps of the structural space need to be filed and membrane proteins as well as intrinsically unstructured proteins still constitute challenging targets. Solving supramolecular assemblies of increasing complexity, developing a “4D biology” for decrypting the kinematic changes in macromolecular structures in action, integrating these structural data in the whole cell organization, and deciphering biomedical implications will represent the new frontiers.",,"['Giegé, Richard', 'Sauter, Claude']",,,,
,PMC,Multiplexed Luminex xMAP Assay for Detection and Identification of Five Adenovirus Serotypes Associated with Epidemics of Respiratory Disease in Adults,http://dx.doi.org/10.1128/JCM.00029-10,PMC2884482,,,"Several serotypes of human adenovirus (HAdV) cause acute respiratory disease (ARD) among healthy adults, sometimes generating broad outbreaks with high attack rates and occasional fatalities. Timely serotype identification provides valuable epidemiological information and significantly contributes to prevention (vaccination) strategies. The prevalence of specific serotypes causing ARD varies geographically. HAdV-3, HAdV-4, HAdV-7, HAdV-14, and HAdV-21 are the serotypes most commonly found in adult populations in the Western Hemisphere. Unfortunately, conventional serotype identification is a tedious process which can take a week or longer. For this reason, new molecular methods for serotype identification are needed. Commercially available rapid antigen and PCR assays for the detection of HAdV are universal but do not distinguish between the different serotypes. We describe the development of a sensitive and specific multiplex assay capable of identifying serotypes 3, 4, 7, 14, and 21. Two sets of primers were used for nonspecific (universal) PCR amplification, and serotype-specific probes coupled to Luminex tags were used for target-specific extension (TSE). PCR and TSE primers were designed using known hexon gene sequences of HAdV. The TSE products of HAdV-3, HAdV-4, HAdV-7, HAdV-14, and HAdV-21 were correctly identified using the Luminex xMAP fluid microsphere-based array system. No cross-reactivity with other respiratory pathogens or other HAdV serotypes was observed. This multiplexed assay can be expanded to include more serotypes and will allow broad and rapid detection and identification of adenoviral serotypes in a high-throughput environment.",,"['Washington, Cicely', 'Metzgar, David', 'Hazbón, Manzour Hernando', 'Binn, Leonard', 'Lyons, Arthur', 'Coward, Carl', 'Kuschner, Robert']",,,,
,PMC,The Crystal Structure of Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein Nsp1β Reveals a Novel Metal-Dependent Nuclease,http://dx.doi.org/10.1128/JVI.00301-10,PMC2903276,,,"Porcine reproductive and respiratory syndrome virus (PRRSV), a member of the Arteriviridae family of Nidovirales, is the causative agent of porcine reproductive and respiratory syndrome, which results in enormous economic losses in the swine industry. As the second protein encoded by the PRRSV genome, nsp1β cleaves itself from the downstream nsp2 protein via a C-terminal papain-like cysteine protease (PCP) domain. Although nsp1β is known to be involved in virulence, its precise role in the process of viral infection remains unclear. In this work, we describe the homodimeric crystal structure of PRRSV nsp1β in its natural, self-processed form. We show that the architecture of its N-terminal domain (NTD) adopts a fold closely resembling that of several known nucleases and has intrinsic nuclease activity that is strongly activated by manganese ions in vitro. Key features, however, distinguish nsp1β from characterized nucleases, including the C-terminal PCP domain (which is responsible for the self-release of nsp1β from nsp2), a linker domain (LKD) that connects the NTD and the PCP domain, and a C-terminal extension (CTE) that binds to and is stabilized by the putative substrate binding site of the PCPβ domain. Combined with the reported nuclear localization of this protein, these results shed light on the self-processing mode and precise biological function of nsp1β and thus offer a multitarget template for future drug discovery.",,"['Xue, Fei', 'Sun, Yuna', 'Yan, Liming', 'Zhao, Cong', 'Chen, Ji', 'Bartlam, Mark', 'Li, Xuemei', 'Lou, Zhiyong', 'Rao, Zihe']",,,,
,PMC,Role of Mouse Hepatitis Virus (MHV) Receptor Murine CEACAM1 in the Resistance of Mice to MHV Infection: Studies of Mice with Chimeric mCEACAM1a and mCEACAM1b,http://dx.doi.org/10.1128/JVI.02680-09,PMC2903249,,,"Although most inbred mouse strains are highly susceptible to mouse hepatitis virus (MHV) infection, the inbred SJL line of mice is highly resistant to its infection. The principal receptor for MHV is murine CEACAM1 (mCEACAM1). Susceptible strains of mice are homozygous for the 1a allele of mCeacam1, while SJL mice are homozygous for the 1b allele. mCEACAM1a (1a) has a 10- to 100-fold-higher receptor activity than does mCEACAM1b (1b). To explore the hypothesis that MHV susceptibility is due to the different MHV receptor activities of 1a and 1b, we established a chimeric C57BL/6 mouse (cB61ba) in which a part of the N-terminal immunoglobulin (Ig)-like domain of the mCeacam1a (1a) gene, which is responsible for MHV receptor function, is replaced by the corresponding region of mCeacam1b (1b). We compared the MHV susceptibility of these chimeric mice to that of SJL and B6 mice. B6 mice that are homozygous for 1a are highly susceptible to MHV-A59 infection, with a 50% lethal dose (LD(50)) of 10(2.5) PFU, while chimeric cB61ba mice and SJL mice homozygous for 1ba and 1b, respectively, survived following inoculation with 10(5) PFU. Unexpectedly, cB61ba mice were more resistant to MHV-A59 infection than SJL mice as measured by virus replication in target organs, including liver and brain. No infectious virus or viral RNA was detected in the organs of cB61ba mice, while viral RNA and infectious virus were detected in target organs of SJL mice. Furthermore, SJL mice produced antiviral antibodies after MHV-A59 inoculation with 10(5) PFU, but cB61ba mice did not. Thus, cB61ba mice are apparently completely resistant to MHV-A59 infection, while SJL mice permit low levels of MHV-A59 virus replication during self-limited, asymptomatic infection. When expressed on cultured BHK cells, the mCEACAM1b and mCEACAM1ba proteins had similar levels of MHV-A59 receptor activity. These results strongly support the hypothesis that although alleles of mCEACAM1 are the principal determinants of mouse susceptibility to MHV-A59, other as-yet-unidentified murine genes may also play a role in susceptibility to MHV.",,"['Hirai, Asuka', 'Ohtsuka, Nobuhisa', 'Ikeda, Toshio', 'Taniguchi, Rie', 'Blau, Dianna', 'Nakagaki, Keiko', 'Miura, Hideka S.', 'Ami, Yasushi', 'Yamada, Yasuko K.', 'Itohara, Shigeyoshi', 'Holmes, Kathryn V.', 'Taguchi, Fumihiro']",,,,
,PMC,Different profiles of cytokine expression during mild and severe acute pancreatitis,http://dx.doi.org/10.3748/wjg.v16.i15.1845,PMC2856824,,,"AIM: To study secretion patterns of pro- and anti-inflammatory cytokines, and activation of various cellular subsets of leukocytes in peripheral blood. METHODS: We have conducted a prospective observational study. One hundred and eight patients with a diagnosis of acute pancreatitis and onset of the disease within last 72 h were included in this study. The mRNA expression of 25 different types of cytokines in white blood cells was determined by quantitative real time polymerase chain reaction. Levels of 8 different cytokines in blood serum were measured by enzyme linked immunosorbent assay. Clinical data and cytokine expression results were subjected to statistical analysis. RESULTS: Severe and necrotizing acute pancreatitis (AP) is characterized by the significant depletion of circulating lymphocytes. Severe acute pancreatitis is associated with a typical systemic inflammatory response syndrome and over-expression of pro-inflammatory cytokines [interleukin (IL)-6, IL-8, macrophage migration inhibitory factor (MIF)]. Serum IL-6 and MIF concentrations are the best discriminators of severe and necrotizing AP as well as possible fatal outcome during the early course of the disease. CONCLUSION: Deregulation of cellular immune system is a key event leading to severe and necrotizing AP. IL-6 and MIF could be used as early predictors of complications.",,"['Dambrauskas, Zilvinas', 'Giese, Nathalia', 'Gulbinas, Antanas', 'Giese, Thomas', 'Berberat, Pascal O', 'Pundzius, Juozas', 'Barauskas, Giedrius', 'Friess, Helmut']",,,,
,PMC,Direct activation of emmprin and associated pathogenesis by an oncogenic herpesvirus,http://dx.doi.org/10.1158/0008-5472.CAN-09-4663,PMC3202426,,,"Emmprin is a multifunctional glycoprotein expressed by cancer cells and stromal cells in the tumor microenvironment. Through both direct effects within tumor cells and promotion of tumor-stroma interactions, emmprin induces tumor cell invasiveness and regional angiogenesis. The Kaposi’s sarcoma-associated herpesvirus (KSHV) is a common etiology of cancers arising in the setting of immune suppression, including Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL). However, whether emmprin expression and function are regulated by KSHV or other oncogenic viruses in the tumor microenvironment to promote viral cancer pathogenesis remains unknown. Fibroblasts and endothelial cells support latent KSHV infection and represent cellular components of KS lesions. Therefore, we utilized primary human fibroblasts and endothelial cells to determine whether KSHV itself regulates emmprin expression, and whether KSHV-emmprin interactions mediate cell invasiveness. We found that KSHV promotes fibroblast and endothelial cell invasiveness following de novo infection through the upregulation of emmprin, and that this effect is mediated by the KSHV-encoded latency-associated nuclear antigen (LANA). We further validated these findings through our observations that emmprin promotes invasiveness, as well as colony formation, by PEL cells derived from human tumors. Collectively, these data implicate KSHV activation of emmprin as an important mechanism for cancer progression and support the potential utility of targeting emmprin as a novel therapeutic approach for KSHV-associated tumors.",,"['Qin, Zhiqiang', 'Dai, Lu', 'Slomiany, Mark G.', 'Toole, Bryan P.', 'Parsons, Chris']",,,,
,PMC,Lipoteichoic acid from Staphylococcus aureus exacerbates respiratory disease in porcine respiratory coronavirus-infected pigs,http://dx.doi.org/10.1016/j.tvjl.2010.03.001,PMC2932768,,,"The objective of this study was to assess if lipoteichoic acid (LTA), produced by Staphylococcus aureus, exacerbates respiratory disease in porcine respiratory coronavirus (PRCV)-infected pigs, as has previously been shown with lipopolysaccharide. Piglets were inoculated with PRCV and 24 h later with S. aureus LTA. Clinical signs, lung virus titres, inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF) were compared with those of animals in PRCV- and LTA- inoculated control groups. All PRCV-LTA inoculated pigs except one developed severe respiratory disease, whereas clinical signs in the control groups were minimal or absent. Virus titres and grossly visible pulmonary lesions were similar in the PRCV-LTA- and PRCV-inoculated groups and were not detected in the LTA-group. Neutrophil percentages in BALF were higher in the PRCV-LTA than in the PRCV group. There was no significant difference in interferon (IFN)-γ, interleukin (IL)-1, IL-6, IL-12/IL-23 and tumour necrosis factor (TNF)-α concentrations in BALF between the PRCV-LTA and PRCV groups, but levels of IL-6, IL-12/IL-23 and IFN-γ were higher in the PRCV-LTA-inoculated than in the LTA-inoculated controls. The findings suggest that the experimentally-induced respiratory disease was not mediated by cytokine over-production, but rather reflected the concerted action of particular cytokine interactions and/or as yet unidentified mediators. This is the first in vivo study to report the synergistic interaction between a virus and LTA in enhancing the severity of respiratory disease in the pig. Given that Gram-positive bacteria, capable of producing LTA, are commonly found in pig accommodation, the role of this compound in the development of the porcine respiratory disease complex requires further investigation.",,"['Atanasova, Kalina', 'Van Gucht, Steven', 'Barbé, Filip', 'Duchateau, Luc', 'Van Reeth, Kristien']",,,,
,PMC,Lowering mid-life levels of systolic blood pressure as a public health strategy to reduce late-life dementia: Perspective from the Honolulu Heart Program/Honolulu Asia Aging Study,http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.147389,PMC3241740,,,"To estimate the potential benefits towards preventing late-life dementia, of lowering systolic blood pressure [SBP] we estimated the population attributable risk (PAR) of elevated SBP on dementia. Analyses are based on the cohort of 8006 Japanese American men (b. 1900 – 1919) followed since 1965 as a part of the Honolulu Heart Program, continued as the Honolulu Asia Aging Study. Mid-life cardiovascular risk factors and late-life brain function are well described. We estimated the PAR of dementia cases attributed to mid-life SBP, grouped by JCN-7 criteria [<120, 120 – < 140, and ≥ 140 mmHG], taking into account treatment history, confounding factors, and competitive risk for death. The analysis is based on 7878 subjects, including 491 cases of dementia, with a mean interval of 25 years between measurement of BP and dementia diagnosis. Compared to those with SBP <120 mmHG, untreated and <50 years at baseline, 17.7% (95% CI 4.6% – 29.1%) of the cases are attributable to prehypertensive levels (SBP 120 – <140 mmHG) of SBP, translating into 11 excess cases per 1000. Among those who did not report taking anti-hypertensive medication in mid-life, 27% [95%CI 8.9%, 42.1%] of dementia cases can be attributed to systolic BP >120 mmHG, translating into 17 excess cases per 1000. Although PAR estimates for population sub –groups may differ by relative risk for dementia or prevalence of elevated levels of BP, these data suggest reducing mid-life systolic BP is an effective prevention strategy to reduce risk for late-life dementia.",,"['Launer, Lenore J.', 'Hughes, Timothy', 'Yu, Binbing', 'Masaki, Kamal', 'Petrovitch, Helen', 'Ross, G. Webster', 'White, Lon R.']",,,,
,PMC,Erratum to: Liberation of SARS-CoV main protease from the viral polyprotein: N-terminal autocleavage does not depend on the mature dimerization mode,http://dx.doi.org/10.1007/s13238-010-0041-y,PMC4901890,,,,,"['Chen, Shuai', 'Jonas, Felix', 'Shen, Can', 'Hilgenfeld, Rolf']",,,,
,PMC,Weekly Monitoring of Children with Asthma for Infections and Illness During Common Cold Seasons,http://dx.doi.org/10.1016/j.jaci.2010.01.059,PMC2866802,,,"BACKGROUND: Exacerbations of childhood asthma and rhinovirus infections both peak during the spring and fall, suggesting that viral infections are major contributors to seasonal asthma morbidity. OBJECTIVES: To evaluate rhinovirus infections during peak seasons in children with asthma, and to analyze relationships between viral infection and illness severity. METHODS: Fifty-eight children with asthma ages 6-8 years provided 5 consecutive weekly nasal lavage samples during September and April; symptoms, medication use, and peak flow were recorded. Rhinoviruses were identified using multiplex PCR and partial sequencing of viral genomes. RESULTS: Viruses were detected in 36-50% of the specimens, and, 72-99% of the viruses were rhinoviruses. There were 52 different strains (including 16 HRV-C) among the 169 rhinovirus isolates; no strains found in more than two collection periods, and all but two children had a respiratory infection. Virus-positive weeks were associated with greater cold and asthma severity (p<0.0001 and p=0.0002 respectively). Furthermore, virus-positive illnesses had increased duration and severity of cold and asthma symptoms, and more frequent loss of asthma control (47% vs. 22%, p=0.008). While allergen-sensitized vs. non-sensitized children had the same number of viral infections, the former had 47% more symptomatic viral illnesses (1.19 vs. 0.81 per month, p=0.03). CONCLUSIONS: Rhinovirus infections are nearly universal in children with asthma during common cold seasons, likely due to a plethora of new strains appearing each season. Illnesses associated with viruses have greater duration and severity. Finally, atopic asthmatic children experienced more frequent and severe viral-induced illnesses. CLINICAL IMPLICATIONS: The combination of viral infection and allergy increases the morbidity of respiratory illness in children with asthma.",,"['Olenec, Jaime P', 'Kim, Woo Kyung', 'Lee, Wai-Ming', 'Vang, Fue', 'Pappas, Tressa E', 'Salazar, Lisa EP', 'Evans, Michael D', 'Bork, Jack', 'Roberg, Kathleen', 'Lemanske, Robert F', 'Gern, James E']",,,,
,PMC,Quantitative Proteomics Analysis Reveals BAG3 as a Potential Target To Suppress Severe Acute Respiratory Syndrome Coronavirus Replication,http://dx.doi.org/10.1128/JVI.00213-10,PMC2876644,,,"The discovery of a novel coronavirus (CoV) as the causative agent of severe acute respiratory syndrome (SARS) has highlighted the need for a better understanding of CoV replication. The replication of SARS-CoV is highly dependent on host cell factors. However, relatively little is known about the cellular proteome changes that occur during SARS-CoV replication. Recently, we developed a cell line expressing a SARS-CoV subgenomic replicon and used it to screen inhibitors of SARS-CoV replication. To identify host proteins important for SARS-CoV RNA replication, the protein profiles of the SARS-CoV replicon cells and parental BHK21 cells were compared using a quantitative proteomic strategy termed “stable-isotope labeling by amino acids in cell culture-mass spectrometry” (SILAC-MS). Our results revealed that, among the 1,081 host proteins quantified in both forward and reverse SILAC measurements, 74 had significantly altered levels of expression. Of these, significantly upregulated BCL2-associated athanogene 3 (BAG3) was selected for further functional studies. BAG3 is involved in a wide variety of cellular processes, including cell survival, cellular stress response, proliferation, migration, and apoptosis. Our results show that inhibition of BAG3 expression by RNA interference led to significant suppression of SARS-CoV replication, suggesting the possibility that upregulation of BAG3 may be part of the machinery that SARS-CoV relies on for replication. By correlating the proteomic data with these functional studies, the findings of this study provide important information for understanding SARS-CoV replication.",,"['Zhang, Liang', 'Zhang, Zhi-Ping', 'Zhang, Xian-En', 'Lin, Fu-Sen', 'Ge, Feng']",,,,
,PMC,Anti-TNF-α therapy does not ameliorate disease in a model of acute virus-endotoxin mediated respiratory disease in pigs,http://dx.doi.org/10.1016/j.vetimm.2010.04.003,PMC2922464,,,"Tumour necrosis factor-α (TNF-α) has been shown to play a role in many inflammatory conditions. Currently anti-TNF-α drugs (e.g. etanercept) are used in humans for treatment of autoimmune diseases. In this study we aimed to elucidate the role of TNF-α in the development of virus-endotoxin-induced respiratory disease. Twenty-two caesarean derived colostrum deprived pigs were used. Initially, the availability in the lungs and circulation, and possible clinical and inflammatory effects of etanercept alone were assessed in 4 pigs after intratracheal and intraperitoneal administration of 0.5 mg/per route/per pig. High anti-TNF-α activity was detected in bronchoalveolar lavage (BAL) fluids, peritoneal lavage fluids and serum of all animals for at least 8 hours post inoculation (HPI). No clinical symptoms, lung lesions, lung cell infiltration or induction of IFN-α, IL-1, IL-6, IL-12 and TNF-α in BAL were detected. Subsequently, the ability of etanercept to block porcine TNF-α and its effect on the above mentioned parameters and on lung virus titres were assessed in 8 pigs. They were inoculated intratracheally with porcine respiratory coronavirus (PRCV) followed by lipopolysaccharide (LPS) 24 hours later. Etanercept was administered at the time of LPS inoculation via the same routes and dose as in the initial experiment. The parameters were compared with a control group (n=8), receiving only PRCV-LPS. Half of the animals from each group were euthanized at 4 and the rest at 8 hours after LPS inoculation. TNF-α was completely neutralized in 3 of the 4 animals euthanized at 4 HPI and significantly lower than in the PRCV-LPS group at all times. No significant differences in disease severity, lung lesions, virus replication, lung cell infiltration or levels of IFN-α, IL-1, IL-6 and IL-12/IL-23 were observed between the two groups. Blocking of TNF-α alone was not sufficient to ameliorate disease in the PRCV-LPS model of respiratory disease, possibly due to the redundancy in the proinflammatory cytokine cascade, or the involvement of other unidentified disease mediators.",,"['Atanasova, Kalina', 'Van Gucht, Steven', 'Van Reeth, Kristien']",,,,
,PMC,Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine,http://dx.doi.org/10.1172/JCI41902,PMC2860935,,,"The target of neutralizing antibodies that protect against influenza virus infection is the viral protein HA. Genetic and antigenic variation in HA has been used to classify influenza viruses into subtypes (H1–H16). The neutralizing antibody response to influenza virus is thought to be specific for a few antigenically related isolates within a given subtype. However, while heterosubtypic antibodies capable of neutralizing multiple influenza virus subtypes have been recently isolated from phage display libraries, it is not known whether such antibodies are produced in the course of an immune response to influenza virus infection or vaccine. Here we report that, following vaccination with seasonal influenza vaccine containing H1 and H3 influenza virus subtypes, some individuals produce antibodies that cross-react with H5 HA. By immortalizing IgG-expressing B cells from 4 individuals, we isolated 20 heterosubtypic mAbs that bound and neutralized viruses belonging to several HA subtypes (H1, H2, H5, H6, and H9), including the pandemic A/California/07/09 H1N1 isolate. The mAbs used different VH genes and carried a high frequency of somatic mutations. With the exception of a mAb that bound to the HA globular head, all heterosubtypic mAbs bound to acid-sensitive epitopes in the HA stem region. Four mAbs were evaluated in vivo and protected mice from challenge with influenza viruses representative of different subtypes. These findings reveal that seasonal influenza vaccination can induce polyclonal heterosubtypic neutralizing antibodies that cross-react with the swine-origin pandemic H1N1 influenza virus and with the highly pathogenic H5N1 virus.",,"['Corti, Davide', 'Suguitan, Amorsolo L.', 'Pinna, Debora', 'Silacci, Chiara', 'Fernandez-Rodriguez, Blanca M.', 'Vanzetta, Fabrizia', 'Santos, Celia', 'Luke, Catherine J.', 'Torres-Velez, Fernando J.', 'Temperton, Nigel J.', 'Weiss, Robin A.', 'Sallusto, Federica', 'Subbarao, Kanta', 'Lanzavecchia, Antonio']",,,,
,PMC,The Renin Angiotensin System and the Metabolic Syndrome,http://dx.doi.org/10.1016/j.physbeh.2010.03.018,PMC2886177,,,"The renin angiotensin system (RAS; most well-known for its critical roles in the regulation of cardiovascular function and hydromineral balance) has regained the spotlight for its potential roles in various aspects of the metabolic syndrome. It may serve as a causal link among obesity and several co-morbidities. Drugs that reduce the synthesis or action of angiotensin-II (A-II; the primary effector peptide of the RAS) have been used to treat hypertension for decades and, more recently, clinical trials have determined the utility of these pharmacological agents to prevent insulin resistance. Moreover, there is evidence that the RAS contributes to body weight regulation by acting in various tissues. This review summarizes what is known of the actions of the RAS in the brain and throughout the body to influence various metabolic disorders. Special emphasis is given to the role of the RAS in body weight regulation.",,"['de Kloet, Annette D.', 'Krause, Eric G.', 'Woods, Stephen C.']",,,,
,PMC,Extrapulmonary tissue responses in cynomolgus macaques (Macaca fascicularis) infected with highly pathogenic avian influenza A (H5N1) virus,http://dx.doi.org/10.1007/s00705-010-0662-8,PMC2892232,,,"The mechanisms responsible for virulence of influenza viruses in humans remain poorly understood. A prevailing hypothesis is that the highly pathogenic virus isolates cause a severe cytokinemia precipitating acute respiratory distress syndrome and multiple organ dysfunction syndrome. Cynomolgus macaques (Macaca fascicularis) infected with a human highly pathogenic avian influenza (HPAI) H5N1 virus isolate (A/Vietnam/1203/2004) or reassortants of human influenza virus A/Texas/36/91 (H1N1) containing genes from the 1918 pandemic influenza A (H1N1) virus developed severe pneumonia within 24 h postinfection. However, virus spread beyond the lungs was only detected in the H5N1 group, and signs of extrapulmonary tissue reactions, including microglia activation and sustained up-regulation of inflammatory markers, most notably hypoxia inducible factor-1α (HIF-1α), were largely limited to this group. Extrapulmonary pathology may thus contribute to the morbidities induced by H5N1 viruses.",,"['Tolnay, A.-E.', 'Baskin, C. R.', 'Tumpey, T. M.', 'Sabourin, P. J.', 'Sabourin, C. L.', 'Long, J. P.', 'Pyles, J. A.', 'Albrecht, R. A.', 'Garccía-Sastre, A.', 'Katze, M. G.', 'Bielefeldt-Ohmann, H.']",,,,
,PMC,Mutation of Glu-166 Blocks the Substrate-Induced Dimerization of SARS Coronavirus Main Protease,http://dx.doi.org/10.1016/j.bpj.2009.12.4272,PMC2849084,,,"The maturation of SARS coronavirus involves the autocleavage of polyproteins 1a and 1ab by the main protease (Mpro) and a papain-like protease; these represent attractive targets for the development of anti-SARS drugs. The functional unit of Mpro is a homodimer, and each subunit has a His-41⋯Cys-145 catalytic dyad. Current thinking in this area is that Mpro dimerization is essential for catalysis, although the influence of the substrate binding on the dimer formation has never been explored. Here, we delineate the contributions of the peptide substrate to Mpro dimerization. Enzyme kinetic assays indicate that the monomeric mutant R298A/L exhibits lower activity but in a cooperative manner. Analytical ultracentrifugation analyses indicate that in the presence of substrates, the major species of R298A/L shows a significant size shift toward the dimeric form and the monomer-dimer dissociation constant of R298A/L decreases by 12- to 17-fold, approaching that for wild-type. Furthermore, this substrate-induced dimerization was found to be reversible after substrates were removed. Based on the crystal structures, a key residue, Glu-166, which is responsible for recognizing the Gln-P1 of the substrate and binding to Ser-1 of another protomer, will interact with Asn-142 and block the S1 subsite entrance in the monomer. Our studies indicate that mutation of Glu-166 in the R298A mutant indeed blocks the substrate-induced dimerization. This demonstrates that Glu-166 plays a pivotal role in connecting the substrate binding site with the dimer interface. We conclude that protein-ligand and protein-protein interactions are closely correlated in Mpro.",,"['Cheng, Shu-Chun', 'Chang, Gu-Gang', 'Chou, Chi-Yuan']",,,,
,PMC,Studies of culture conditions and environmental stability of human metapneumovirus,http://dx.doi.org/10.1016/j.virusres.2010.03.018,PMC2894476,,,"Human metapneumovirus (HMPV) is a paramyxovirus that is a leading cause of acute respiratory disease. HMPV is difficult to cultivate and limited published data describe the in vitro growth characteristics of the virus and its ability to replicate in different cell lines. Stability of HMPV to different temperatures or environmental conditions has not been described. Nosocomial infections due to HMPV have been reported, and thus the survival of infectious particles on environmental surfaces is important. We tested multiple cell lines for the ability to support HMPV replication both in the presence and absence of exogenous trypsin. The most permissive monkey kidney epithelial cells were LLC-MK2 and Vero, while the most permissive human airway epithelial cell line was BEAS-2B. LLC-MK2 cells were tolerant of trypsin and thus remain an ideal cell line for HMPV cultivation. Spinoculation significantly increased the infectivity of HMPV for cells in monolayer culture. Infectious virus was very stable to repeat freeze-thaw cycles and ambient room temperature or 4°C, while incubation at 37 °C led to degradation of virus titer. Finally, nonporous materials such as metal or plastic retained infectious virus for prolonged periods, while virus deposited on tissue and fabric rapidly lost infectivity. These findings provide guidance for laboratories attempting to culture HMPV and relevant information for infection control policies.",,"['Tollefson, Sharon J.', 'Cox, Reagan G.', 'Williams, John V.']",,,,
,PMC,Preparing for infectious disease threats at mass gatherings: the case of the Vancouver 2010 Olympic Winter Games,http://dx.doi.org/10.1503/cmaj.100093,PMC2845686,,,,,"['Khan, Kamran', 'Freifeld, Clark C.', 'Wang, Jun', 'Mekaru, Sumiko R.', 'Kossowsky, David', 'Sonricker, Amy L.', 'Hu, Wei', 'Sears, Jennifer', 'Chan, Angie', 'Brownstein, John S.']",,,,
,PMC,Pathogenesis of Murine Coronavirus in the Central Nervous System,http://dx.doi.org/10.1007/s11481-010-9202-2,PMC2914825,,,"Murine coronavirus (mouse hepatitis virus, MHV) is a collection of strains that induce disease in several organ systems of mice. Infection with neurotropic strains JHM and A59 causes acute encephalitis, and in survivors, chronic demyelination, the latter of which serves as an animal model for multiple sclerosis. The MHV receptor is a carcinoembryonic antigen-related cell adhesion molecule, CEACAM1a; paradoxically, CEACAM1a is poorly expressed in the central nervous system (CNS), leading to speculation of an additional receptor. Comparison of highly neurovirulent JHM isolates with less virulent variants and the weakly neurovirulent A59 strain, combined with the use of reverse genetics, has allowed mapping of pathogenic properties to individual viral genes. The spike protein, responsible for viral entry, is a major determinant of tropism and virulence. Other viral proteins, both structural and nonstructural, also contribute to pathogenesis in the CNS. Studies of host responses to MHV indicate that both innate and adaptive responses are crucial to antiviral defense. Type I interferon is essential to prevent very early mortality after infection. CD8 T cells, with the help of CD4 T cells, are crucial for viral clearance during acute disease and persist in the CNS during chronic disease. B cells are necessary to prevent reactivation of virus in the CNS following clearance of acute infection. Despite advances in understanding of coronavirus pathogenesis, questions remain regarding the mechanisms of viral entry and spread in cell types expressing low levels of receptor, as well as the unique interplay between virus and the host immune system during acute and chronic disease.",,"['Bender, Susan J.', 'Weiss, Susan R.']",,,,
,PMC,"Acetylation regulates Cyclophilin A catalysis, immunosuppression and HIV isomerisation",http://dx.doi.org/10.1038/nchembio.342,PMC3867001,,,"Cyclophilin A (CypA) is a ubiquitous cis-trans-prolyl isomerase with key roles in immunity and viral infection. CypA suppresses T-cell activation through cyclosporine (Cs) complexation and is required for effective HIV-1 replication in host cells. We show that CypA is acetylated in diverse human cell lines and use a synthetically evolved acetyl-lysyl-tRNA synthetase/tRNA(CUA) pair to produce recombinant acetylated CypA in E. coli. We determine atomic resolution structures of acetylated CypA and its complexes with Cs and HIV-1 capsid. Acetylation dramatically inhibits CypA catalysis of cis to trans isomerisation and stabilises cis rather than trans forms of the HIV-1 capsid. Furthermore, CypA acetylation antagonizes the immunosuppressive effects of Cs, by inhibiting the sequential steps of Cs binding and calcineurin inhibition. Our results reveal that acetylation regulates key functions of CypA in immunity and viral infection and provide a general set of mechanisms by which acetylation modulates interactions to regulate cell function.",,"['Lammers, Michael', 'Neumann, Heinz', 'Chin, Jason W.', 'James, Leo C.']",,,,
,PMC,Using Time-Structured Data to Estimate Evolutionary Rates of Double-Stranded DNA Viruses,http://dx.doi.org/10.1093/molbev/msq088,PMC3107591,,,"Double-stranded (ds) DNA viruses are often described as evolving through long-term codivergent associations with their hosts, a pattern that is expected to be associated with low rates of nucleotide substitution. However, the hypothesis of codivergence between dsDNA viruses and their hosts has rarely been rigorously tested, even though the vast majority of nucleotide substitution rate estimates for dsDNA viruses are based upon this assumption. It is therefore important to estimate the evolutionary rates of dsDNA viruses independent of the assumption of host-virus codivergence. Here, we explore the use of temporally structured sequence data within a Bayesian framework to estimate the evolutionary rates for seven human dsDNA viruses, including variola virus (VARV) (the causative agent of smallpox) and herpes simplex virus-1. Our analyses reveal that although the VARV genome is likely to evolve at a rate of approximately 1 × 10(−5) substitutions/site/year and hence approaching that of many RNA viruses, the evolutionary rates of many other dsDNA viruses remain problematic to estimate. Synthetic data sets were constructed to inform our interpretation of the substitution rates estimated for these dsDNA viruses and the analysis of these demonstrated that given a sequence data set of appropriate length and sampling depth, it is possible to use time-structured analyses to estimate the substitution rates of many dsDNA viruses independently from the assumption of host-virus codivergence. Finally, the discovery that some dsDNA viruses may evolve at rates approaching those of RNA viruses has important implications for our understanding of the long-term evolutionary history and emergence potential of this major group of viruses.",,"['Firth, Cadhla', 'Kitchen, Andrew', 'Shapiro, Beth', 'Suchard, Marc A.', 'Holmes, Edward C.', 'Rambaut, Andrew']",,,,
,PMC,Characteristic of Dengue Disease in Taiwan: 2002–2007,http://dx.doi.org/10.4269/ajtmh.2010.09-0549,PMC2844571,,,"Taiwan's dengue outbreaks have a unique type of transmission: starting by import from abroad in early summer, spreading out locally, and ending in the winter. This pattern repeats every year. Most of the dengue patients are adults, with dengue fever peaking in the 50–54 year age range, and dengue hemorrhagic fever in the 60–64 year age range. Two patterns of dengue infection were found: DENV-2 in 2002 with 74% of secondary infection in contrast to non-DENV-2 (DENV-1 or DENV-3) in 2004–2007 with ~70% of primary infection. Secondary dengue virus infection increases disease morbidity, but not mortality in adults. The active serological surveillance shows two-thirds of the dengue-infected adults are symptomatic post infection. The Taiwanese experience of adult dengue should be valuable for countries or areas where, although dengue is not endemic, the Aedes aegypti vector exists and dengue virus can be introduced by travelers.",,"['Lin, Chien-Chou', 'Huang, Yh-Hsiung', 'Shu, Pei-Yun', 'Wu, Ho-Sheng', 'Lin, Yee-Shin', 'Yeh, Trai-Ming', 'Liu, Hsiao-Sheng', 'Liu, Ching-Chuan', 'Lei, Huan-Yao']",,,,
,PMC,T-cell antigen receptor (TCR) transmembrane peptides: A new paradigm for the treatment of autoimmune diseases,,PMC2900625,,,"Cell surface membranes are generally considered as inert and hydrophobic providing a stable physical barrier that anchor proteins and maintain cellular homeostasis between the intra- and the extra-cellular environment. The integral proteins that transverse membranes do so once or multiple times and can function alone or as part of a larger complex. Far from being inert, there is a multiplicity of biophysical factors that drive protein-protein and protein-lipid interactions within membranes that are being increasingly recognised as very important for cellular function. Unravelling these “hot-spots” on the contact surface of transmembrane (TM) proteins and targeting peptides to these sites to interrupt the cohesive interaction between the proteins provides both an enormous challenge and a huge therapeutic potential that as yet remains unrecognized. Indeed, with biopharmaceutical research on the rise, TM peptides may prove a useful innovation. Using the T-cell antigen receptor (TCR) as a model system of multi-subunits interacting at the TM via electrostatic charges the potential for peptides as therapeutic agents to interfere with normal immune responses is discussed. The principles of such can be extended to other similar receptor systems including those involved in cancer or infection.",,"['Manolios, Nicholas', 'Ali, Marina', 'Bender, Vera']",,,,
,PMC,New therapeutic strategies targeting transmembrane signal transduction in the immune system,,PMC2900623,,,"Single-chain receptors and multi-chain immune recognition receptors (SRs and MIRRs, respectively) represent families of structurally related but functionally different surface receptors expressed on different cells. In contrast to SRs, a distinctive and common structural characteristic of MIRR family members is that the extracellular recognition domains and intracellular signaling domains are located on separate subunits. How extracellular ligand binding triggers MIRRs and initiates intracellular signal transduction processes is not clear. A novel model of immune signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) model, suggests that the homooligomerization of receptor intracellular signaling domains represents a necessary and sufficient condition for receptor triggering. In this review, I demonstrate striking similarities between a consensus model of SR signaling and the SCHOOL model of MIRR signaling and show how these models, together with the lessons learned from viral pathogenesis, provide a molecular basis for novel pharmacological approaches targeting inter- and intrareceptor transmembrane interactions as universal therapeutic targets for a diverse variety of immune and other disorders.",,"Sigalov, Alexander B",,,,
,PMC,The Changing Microbial Epidemiology in Cystic Fibrosis,http://dx.doi.org/10.1128/CMR.00068-09,PMC2863368,,,"Summary: Infection of the airways remains the primary cause of morbidity and mortality in persons with cystic fibrosis (CF). This review describes salient features of the epidemiologies of microbial species that are involved in respiratory tract infection in CF. The apparently expanding spectrum of species causing infection in CF and recent changes in the incidences and prevalences of infection due to specific bacterial, fungal, and viral species are described. The challenges inherent in tracking and interpreting rates of infection in this patient population are discussed.",,"LiPuma, John J.",,,,
,PMC,"A Global Perspective on Hantavirus Ecology, Epidemiology, and Disease",http://dx.doi.org/10.1128/CMR.00062-09,PMC2863364,,,"Summary: Hantaviruses are enzootic viruses that maintain persistent infections in their rodent hosts without apparent disease symptoms. The spillover of these viruses to humans can lead to one of two serious illnesses, hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome. In recent years, there has been an improved understanding of the epidemiology, pathogenesis, and natural history of these viruses following an increase in the number of outbreaks in the Americas. In this review, current concepts regarding the ecology of and disease associated with these serious human pathogens are presented. Priorities for future research suggest an integration of the ecology and evolution of these and other host-virus ecosystems through modeling and hypothesis-driven research with the risk of emergence, host switching/spillover, and disease transmission to humans.",,"['Jonsson, Colleen B.', 'Figueiredo, Luiz Tadeu Moraes', 'Vapalahti, Olli']",,,,
,PMC,Early observational research and registries during the 2009–2010 influenza A pandemic,http://dx.doi.org/10.1097/CCM.0b013e3181d20c77,PMC3705715,,,"As a critical care community, we have an obligation to provide not only clinical care but also the research that guides initial and subsequent clinical responses during a pandemic. There are many challenges to conducting such research. The first is speed of response. However, given the near inevitability of certain events, for example, viral respiratory illness such as the 2009 pandemic, geographically circumscribed natural disasters, or acts of terror, many study and trial designs should be preplanned and modified quickly when specific events occur. Template case report forms should be available for modification and web entry; centralized research ethics boards and funders should have the opportunity to preview and advise on such research beforehand; and national and international research groups should be prepared to work together on common studies and trials for common challenges. We describe the early international critical care research response to the influenza A 2009 (H1N1) pandemic, including specifics of observational study case report form, registry, and clinical trial design, cooperation of international critical care research organizations, and the early results of these collaborations.",,"['Fowler, Robert A.', 'Webb, Steven A. R.', 'Rowan, Kathy M.', 'Sprung, Charles L.', 'Thompson, B. Taylor', 'Randolph, Adrienne G.', 'Jouvet, Philippe', 'Lapinsky, Stephen', 'Rubinson, Lewis', 'Rello, Jordi', 'Cobb, J. Perren', 'Rice, Todd W.', 'Uyeki, Tim', 'Marshall, John C.']",,,,
,PMC,The 1918 influenza pandemic: Lessons for 2009 and the future,http://dx.doi.org/10.1097/CCM.0b013e3181ceb25b,PMC3180813,,,"The 1918 to 1919 H1N1 influenza pandemic is among the most deadly events in recorded human history, having killed an estimated 50 to 100 million persons. Recent H5N1 avian influenza epizootics associated with sporadic human fatalities have heightened concern that a new influenza pandemic, one at least as lethal as that of 1918, could be developing. In early 2009, a novel pandemic H1N1 influenza virus appeared, but it has not exhibited unusually high pathogenicity. Nevertheless, because this virus spreads globally, some scientists predict that mutations will increase its lethality. Therefore, to accurately predict, plan, and respond to current and future influenza pandemics, we must first better-understand the events and experiences of 1918. Although the entire genome of the 1918 influenza virus has been sequenced, many questions about the pandemic it caused remain unanswered. In this review, we discuss the origin of the 1918 pandemic influenza virus, the pandemic’s unusual epidemiologic features and the causes and demographic patterns of fatality, and how this information should impact our response to the current 2009 H1N1 pandemic and future pandemics. After 92 yrs of research, fundamental questions about influenza pandemics remain unanswered. Thus, we must remain vigilant and use the knowledge we have gained from 1918 and other influenza pandemics to direct targeted research and pandemic influenza preparedness planning, emphasizing prevention, containment, and treatment.",,"['Morens, David M.', 'Taubenberger, Jeffery K.', 'Harvey, Hillery A.', 'Memoli, Matthew J.']",,,,
,PMC,ADAM-17: The Enzyme That Does It All,http://dx.doi.org/10.3109/10409231003628015,PMC2841225,,,"This review focuses on the role of ADAM-17 in disease. Since its debut as the tumor necrosis factor converting enzyme or TACE, ADAM-17 has been reported to be an indispensible regulator of almost every cellular event from proliferation to migration. The central role of ADAM-17 in cell regulation is rooted in its diverse array of substrates: cytokines, growth factors, and their receptors as well as adhesion molecules are activated or inactivated by their cleavage with ADAM-17. It is therefore not surprising that ADAM-17 is implicated in numerous human diseases including cancer, heart disease, diabetes, rheumatoid arthritis, kidney fibrosis, Alzheimer’s disease, and is a promising target for future treatments. The specific role of ADAM-17 in the pathophysiology of these diseases is very complex and depends on the cellular context. To exploit the therapeutic potential of ADAM-17, it is important to understand how its activity is regulated and how specific organs and cells can be targeted to inactivate or activate the enzyme.",,"Gooz, Monika",,,,
,PMC,The role of rhinovirus infections in the development of early childhood asthma,http://dx.doi.org/10.1097/ACI.0b013e3283352f7c,PMC2932662,,,"PURPOSE OF REVIEW: To discuss the role of rhinoviruses (HRVs) in early childhood wheezing illnesses and how HRVs contribute to the development of childhood asthma. RECENT FINDINGS: Advanced molecular diagnostics have identified HRVs as pathogens frequently causing wheezing illnesses in infants and young children. Wheezing during HRV infection in early life identifies children at particularly high-risk of asthma development. Plausible mechanisms by which HRV could cause airway damage, promote airway remodeling, and lead to asthma development have recently been identified. SUMMARY: HRV is a significant source of morbidity in infants and young children. This review identifies mechanisms by which HRV lower respiratory tract infection, particularly in a susceptible host, could promote the development of childhood asthma. Further studies are needed to elucidate the mechanisms underlying the link between HRV wheezing in early childhood and subsequent asthma development, with the critical goal of identifying novel therapeutic and prevention strategies for both early childhood wheezing and asthma.",,"Jackson, Daniel J.",,,,
,PMC,Myriad Genetics: In the eye of the policy storm,http://dx.doi.org/10.1097/GIM.0b013e3181d72661,PMC3037261,,,"From the late 1980s, a storm surrounding the wisdom, ethics, and economics of human gene patents has been brewing. The various winds of concern in this storm touched on the impact of gene patents on basic and clinical research, on health care delivery, and on the ability of public health care systems to provide equal access when faced with costly patented genetic diagnostic tests. Myriad Genetics, Inc., along with its subsidiary, Myriad Genetic Laboratories, Inc., a small Utah-based biotechnology company, found itself unwittingly in the eye of this storm after a series of decisions it made regarding the commercialization of a hereditary breast cancer diagnostic test. This case study examine the background to Myriad's decisions, the context in which these decisions were made and the policy, research and business response to them.",,"['Gold, E. Richard', 'Carbone, Julia']",,,,
,PMC,Control of Extensively Drug-Resistant Tuberculosis (XDR-TB): A Root Cause Analysis,,PMC3324909,,,"The threat of global infectious agents has the potential to cripple national and global economies, as the outbreaks of SARS, Avian Flu, H1N1, and XDR-TB have demonstrated. This article offers a Root Cause Analysis (RCA) of one public health case study – the Speaker case of XDR-TB – pinpointing the underlying causal relationships associated with this global health incident and proposing recommendations for preventing its recurrence. An RCA approach identifies corrective actions directed at the root causes of the problem and advances them as necessary to eliminate global contagion with its major international public health risks. To my knowledge, this is the first root cause analysis of a global health problem. The reform this article proposes would be to add a standardized procedure akin to the informed consent process in clinical ethics, but within a shared health governance framework. This approach, addressing infectious agents at their origins or source, is potentially a more effective strategy to reduce uncertainty and avert global health threats.",,"Ruger, Jennifer Prah",,,,
,PMC,Human coronaviruses are uncommon in patients with gastrointestinal illness,http://dx.doi.org/10.1016/j.jcv.2010.03.007,PMC2864800,,,"BACKGROUND: Coronaviruses infect numerous animal species causing a variety of illnesses including respiratory, neurologic and enteric disease. Human coronaviruses (HCoV) are mainly associated with respiratory tract disease but have been implicated in enteric disease. OBJECTIVES: To investigate the frequency of coronaviruses in stool samples from children and adults with gastrointestinal illness by RT-PCR. STUDY DESIGN: Clinical samples submitted for infectious diarrhea testing were collected from December 2007 through March 2008. RNA extraction and RT-PCR was performed for stools negative for Clostridium difficile using primer sets against HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1. Clinical data from samples positive for coronaviruses were reviewed and recorded. RESULTS: Samples from 479 patients were collected including 151 pediatric (<= 18yrs), and 328 adults (> 18yrs). Of these samples, 4 patients (1.3%, 2 adult; 2 pediatric) screened positive for the presence of a coronavirus. All detected coronaviruses were identified as HCoV-HKU1. No stools screened positive for either HCoV-229E, HCoV-NL63 or HCoV-OC43. All HCoV-HKU1 positive samples occurred between mid January to mid February. Clinical manifestations from HCoV-HKU1 positive patients included diarrhea, emesis and respiratory complaints. Three (75%) patients were admitted to the hospital with a median length of stay of 6 days. CONCLUSIONS: Coronaviruses as a group are not commonly identified in stool samples of patients presenting with gastrointestinal illness. HCoV-HKU1 can be identified in stool samples from children and adults with gastrointestinal disease, with most individuals having respiratory findings as well. No stool samples screened positive for HCoV-NL63, HCoV-229E, or HCoV-OC43.",,"['Esper, Frank', 'Ou, Zhen', 'Huang, Yung T.']",,,,
,PMC,Identification and structural definition of H5-specific CTL epitopes restricted by HLA-A*0201 derived from the H5N1 subtype of influenza A viruses,http://dx.doi.org/10.1099/vir.0.016766-0,PMC2888162,,,"The haemagglutinin (HA) glycoprotein of influenza A virus is a major antigen that initiates humoral immunity against infection; however, the cellular immune response against HA is poorly understood. Furthermore, HA-derived cytotoxic T-lymphocyte (CTL) epitopes are relatively rare in comparison to other internal gene products. Here, CTL epitopes of the HA serotype H5 protein were screened. By using in silico prediction, in vitro refolding and a T2 cell-binding assay, followed by immunization of HLA-A2.1/K(b) transgenic mice, an HLA-A*0201-restricted decameric epitope, RI-10 (H5 HA205–214, RLYQNPTTYI), was shown to elicit a robust CTL epitope-specific response. In addition, RI-10 and its variant, KI-10 (KLYQNPTTYI), were also demonstrated to be able to induce a higher CTL epitope-specific response than the influenza A virus dominant CTL epitope GL-9 (GILGFVFTL) in peripheral blood mononuclear cells of HLA-A*0201-positive patients who had recovered from H5N1 virus infection. Furthermore, the crystal structures of RI-10–HLA-A*0201 and KI-10–HLA-A*0201 complexes were determined at 2.3 and 2.2 Å resolution, respectively, showing typical HLA-A*0201-restricted epitopes. The conformations of RI-10 and KI-10 in the antigen-presenting grooves in crystal structures of the two complexes show significant differences, despite their nearly identical sequences. These results provide implications for the discovery of diagnostic markers and the design of novel influenza vaccines.",,"['Sun, Yeping', 'Liu, Jun', 'Yang, Meng', 'Gao, Feng', 'Zhou, Jianfang', 'Kitamura, Yoshihiro', 'Gao, Bin', 'Tien, Po', 'Shu, Yuelong', 'Iwamoto, Aikichi', 'Chen, Zhu', 'Gao, George F.']",,,,
,PMC,Activation of Interferon Response Through Toll-Like Receptor 3 Impacts Viral Pathogenesis and Pulmonary Toll-Like Receptor Expression During Respiratory Syncytial Virus and Influenza Infections in the Cotton Rat Sigmodon hispidus Model,http://dx.doi.org/10.1089/jir.2009.0025,PMC2882628,,,"Interferon (IFN) therapy in humans often causes flu-like symptoms by an unknown mechanism. Poly ICLC is a synthetic dsRNA and a Toll-like receptor 3 (TLR3) agonist with a strong IFN-inducing ability. In this work, we analyzed the effect of poly ICLC on pulmonary responses to influenza and respiratory syncytial virus (RSV) infections in the cotton rat (Sigmodon hispidus) model. Viral replication, pulmonary inflammation, and expression of IFN, TLR, and chemokines were monitored and compared. Antiviral effect of poly ICLC against influenza virus and RSV was best achieved at high poly ICLC concentrations that, in the absence of virus infection, induced a strong IFN response. The antiviral doses of poly ICLC, however, also increased lung inflammation, an unexpected finding because of the reported poly ICLC safety in BALB/c mice. Similarly, in contrast to murine model, pathology of RSV infection was increased in cotton rats treated with poly ICLC. Augmented lung inflammation was accompanied by an earlier induction of IFN and TLR responses and a stronger chemokine expression. Overall, these findings indicate significant association between antiviral IFN action and pulmonary inflammation and highlight important animal model-specific variations in the potential of IFN to cause pathology.",,"['Boukhvalova, Marina S.', 'Sotomayor, Talia B.', 'Point, Ryan C.', 'Pletneva, Lioubov M.', 'Prince, Gregory A.', 'Blanco, Jorge C.G.']",,,,
,PMC,Local production of inflammatory mediators during childhood parainfluenza virus infection,http://dx.doi.org/10.1097/INF.0b013e3181d5da2a,PMC3417758,,,"OBJECTIVE: To describe the clinical manifestations of PIV infection and to characterize biochemical markers of PIV disease severity. PATIENTS AND METHODS: We reviewed the medical records of 165 children who had a nasal wash culture positive for PIV at our institution between 1998 and 2008. Nasal wash samples were assayed for 26 inflammatory mediators using Luminex bead proteomics. RESULTS: 153 patients, ages 2 weeks to 12 years, with single virus infection were included in our final analysis. 52 patients were infected with PIV1, 19 with PIV2, 74 with PIV3, and 8 with PIV4. LRTI was diagnosed in 67 (44%) patients, 21 (14%) had LTB, and 49 (32%) had a URI other than LTB. LRTI was diagnosed in 54% of patients infected with PIV3, 35% of those infected with PIV1, 26% of those with PIV2 and 50% of those with PIV4. Compared to uninfected control patients, PIV-infected patients had higher nasal wash concentrations of interleukin (IL)-6, CXCL8 (IL-8), CCL3 (macrophage inflammatory protein (MIP)-1α), CCL4 (MIP-1β), CXCL9 (monokine induced by interferon gamma (MIG) and CCL5 (regulated upon activation, normal T cell expressed and secreted (RANTES). Patients with LRTI, moderate or severe illness, and respirovirus infection (PIV 1 or 3) had higher nasal wash concentrations of CXCL8 when compared to patients with URI, mild illness, or rubulavirus infection (PIV 2 and 4) (p<0.05). CONCLUSIONS: PIV infection causes a spectrum of illnesses associated with the expression and release of several proinflammatory mediators. Of note, elevated levels of CXCL8 in nasal wash samples are associated with more severe forms of PIV disease.",,"['El Feghaly, Rana E.', 'McGann, Lindsay', 'Bonville, Cynthia A.', 'Branigan, Patrick J.', 'Suryadevera, Manika', 'Rosenberg, Helene F.', 'Domachowske, Joseph B.']",,,,
,PMC,Monoclonal antibodies — a proven and rapidly expanding therapeutic modality for human diseases,http://dx.doi.org/10.1007/s13238-010-0052-8,PMC4875100,,,"The study of antibodies has been a focal point in modern biology and medicine since the early 1900s. However, progress in therapeutic antibody development was slow and intermittent until recently. The first antibody therapy, murine-derived murononab OKT3 for acute organ rejection, was approved by the US Food and Drug Administration (FDA) in 1986, more than a decade after César Milstein and Georges Köhler developed methods for the isolation of mouse monoclonal antibodies from hybridoma cells in 1975. As a result of the scientific, technological, and clinical breakthroughs in the 1980s and 1990s, the pace of therapeutic antibody discovery and development accelerated. Antibodies are becoming a major drug modality with more than two dozen therapeutic antibodies in the clinic and hundreds more in development. Despite the progress, need for improvement exists at every level. Antibody therapeutics provides fertile ground for protein scientists to fulfill the dream of personalized medicine through basic scientific discovery and technological innovation.",,"An, Zhiqiang",,,,
,PMC,Three-dimensional domain swapping as a mechanism to lock the active conformation in a super-active octamer of SARS-CoV main protease,http://dx.doi.org/10.1007/s13238-010-0044-8,PMC4875095,,,"Proteolytic processing of viral polyproteins is indispensible for the lifecycle of coronaviruses. The main protease (M(pro)) of SARS-CoV is an attractive target for anti-SARS drug development as it is essential for the polyprotein processing. M(pro) is initially produced as part of viral polyproteins and it is matured by autocleavage. Here, we report that, with the addition of an N-terminal extension peptide, M(pro) can form a domain-swapped dimer. After complete removal of the extension peptide from the dimer, the mature M(pro) self-assembles into a novel super-active octamer (AO-M(pro)). The crystal structure of AO-M(pro) adopts a novel fold with four domain-swapped dimers packing into four active units with nearly identical conformation to that of the previously reported M(pro) active dimer, and 3D domain swapping serves as a mechanism to lock the active conformation due to entanglement of polypeptide chains. Compared with the previously well characterized form of M(pro), in equilibrium between inactive monomer and active dimer, the stable AO-M(pro) exhibits much higher proteolytic activity at low concentration. As all eight active sites are bound with inhibitors, the polyvalent nature of the interaction between AO-M(pro) and its polyprotein substrates with multiple cleavage sites, would make AO-M(pro) functionally much more superior than the M(pro) active dimer for polyprotein processing. Thus, during the initial period of SARS-CoV infection, this novel active form AOM(pro) should play a major role in cleaving polyproteins as the protein level is extremely low. The discovery of AOM(pro) provides new insights about the functional mechanism of M(pro) and its maturation process. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s13238-010-0044-8 and is accessible for authorized users.",,"['Zhang, Shengnan', 'Zhong, Nan', 'Xue, Fei', 'Kang, Xue', 'Ren, Xiaobai', 'Chen, Jiaxuan', 'Jin, Changwen', 'Lou, Zhiyong', 'Xia, Bin']",,,,
,PMC,Roles of the hemagglutinin of influenza A virus in viral entry and development of antiviral therapeutics and vaccines,http://dx.doi.org/10.1007/s13238-010-0054-6,PMC4728157,,,"Seasonal influenza epidemics and influenza pandemics caused by influenza A virus (IAV) has resulted in millions of deaths in the world. The development of anti-IAV vaccines and therapeutics is urgently needed for prevention and treatment of IAV infection and for controlling future influenza pandemics. Hemagglutinin (HA) of IAV plays a critical role in viral binding, fusion and entry, and contains the major neutralizing epitopes. Therefore, HA is an attractive target for developing anti-IAV drugs and vaccines. Here we have reviewed the recent progress in study of conformational changes of HA during viral fusion process and development of HA-based antiviral therapeutics and vaccines.",,"['Jiang, Shibo', 'Li, Runming', 'Du, Lanying', 'Liu, Shuwen']",,,,
,PMC,LSm1-7 complexes bind to specific sites in viral RNA genomes and regulate their translation and replication,http://dx.doi.org/10.1261/rna.1712910,PMC2844628,,,"LSm1-7 complexes promote cellular mRNA degradation, in addition to translation and replication of positive-strand RNA viruses such as the Brome mosaic virus (BMV). Yet, how LSm1-7 complexes act on their targets remains elusive. Here, we report that reconstituted recombinant LSm1-7 complexes directly bind to two distinct RNA-target sequences in the BMV genome, a tRNA-like structure at the 3′-untranslated region and two internal A-rich single-stranded regions. Importantly, in vivo analysis shows that these sequences regulate the translation and replication of the BMV genome. Furthermore, both RNA-target sequences resemble those found for Hfq, the LSm counterpart in bacteria, suggesting conservation through evolution. Our results provide the first evidence that LSm1-7 complexes interact directly with viral RNA genomes and open new perspectives in the understanding of LSm1-7 functions.",,"['Galão, Rui Pedro', 'Chari, Ashwin', 'Alves-Rodrigues, Isabel', 'Lobão, Daniela', 'Mas, Antonio', 'Kambach, Christian', 'Fischer, Utz', 'Díez, Juana']",,,,
,PMC,Nitric oxide is elicited and inhibits viral replication in pigs infected with porcine respiratory coronavirus but not porcine reproductive and respiratory syndrome virus,http://dx.doi.org/10.1016/j.vetimm.2010.03.022,PMC2902704,,,"There is little information on the role of nitric oxide ((•)NO) in innate immunity to respiratory coronavirus (CoV) infections. We examined (•)NO levels by Greiss assay in bronchoalveolar lavage (BAL) of pigs infected with either porcine respiratory coronavirus (PRCV) or porcine reproductive and respiratory syndrome virus (PRRSV), a member of Nidovirales, like CoV. The antiviral effects of (•)NO on these two viruses were tested in an in vitro system using a (•)NO donor, S-nitroso-N-acetylpenicillamine (SNAP). We detected a large increase in (•)NO levels in BAL fluids of PRCV-infected pigs, but not in PRRSV-infected pigs. Pulmonary epithelial cell necrosis induced by PRCV coincided with increased (•)NO. Moreover, (•)NO levels in cell culture medium of PRRSV-infected alveolar macrophages (AMs) did not differ from that of mock-infected AMs. Antiviral assays showed that (•)NO significantly inhibited PRCV replication in swine testicular (ST) cells, whereas PRRSV was not susceptible to (•)NO based on the conditions tested. Our study suggests that unlike PRRSV which induces apoptosis in AMs, respiratory CoVs such as PRCV that infect pulmonary epithelial cells and cause cytolysis, induce (•)NO production in the respiratory tract. Thus, (•)NO may play a role in innate immunity to respiratory CoV infections by inhibiting viral replication.",,"['Jung, Kwonil', 'Gurnani, Ashita', 'Renukaradhya, Gourapura J.', 'Saif, Linda J.']",,,,
,PMC,A 219-mer CHO-Expressing Receptor-Binding Domain of SARS-CoV S Protein Induces Potent Immune Responses and Protective Immunity,http://dx.doi.org/10.1089/vim.2009.0090,PMC2883479,,,"Development of vaccines is essential for the prevention of future recurrences of severe acute respiratory syndrome (SARS), caused by the SARS coronavirus (SARS-CoV). The spike (S) protein, especially receptor-binding domain (RBD) of SARS-CoV, plays important roles in the prevention of SARS infection, and is thus an important component in SARS vaccine development. In this study, we expressed a 219-mer (residues 318–536) RBD protein in Chinese hamster ovary (CHO)-K1 cells (RBD219-CHO), and tested its immune responses and protective immunity in a mouse model. The results showed that this recombinant protein was correctly folded, being able to maintain intact conformation and authentic antigenicity. It could induce strong humoral and cellular immune responses and high titers of neutralizing antibodies in the vaccinated mice. RBD219-CHO protein elicited potent protective immunity that protected all vaccinated mice from SARS-CoV challenge. These results suggest that the recombinant RBD219-CHO protein has great potential for the development of an effective and safe SARS subunit vaccine.",,"['Du, Lanying', 'Zhao, Guangyu', 'Chan, Chris CS', 'Li, Lin', 'He, Yuxian', 'Zhou, Yusen', 'Zheng, Bo-Jian', 'Jiang, Shibo']",,,,
,PMC,Evaluation of New Rapid Antigen Test for Detection of Pandemic Influenza A/H1N1 2009 Virus,http://dx.doi.org/10.1128/JCM.02392-09,PMC2884507,,,"We evaluated the SD Bioline Influenza Ag A/B/A(H1N1) Pandemic test kit and compared it with real-time reverse transcriptase PCR (RT-PCR) for its ability to detect H1N1 2009. The sensitivity and specificity of the test kit for H1N1 2009 were 77% and 100%, respectively.",,"['Choi, Young Jin', 'Kim, Hwi Jun', 'Park, Joon Soo', 'Oh, Myung Ho', 'Nam, Hae Seon', 'Kim, Yong Bae', 'Cho, Byung Ki', 'Ji, Mi Jung', 'Oh, Jin Sik']",,,,
,PMC,Comparison of the Luminex Respiratory Virus Panel Fast Assay with In-House Real-Time PCR for Respiratory Viral Infection Diagnosis,http://dx.doi.org/10.1128/JCM.02446-09,PMC2884497,,,"The Luminex xTAG Respiratory Virus Panel (RVP) assay has been shown to offer improved diagnostic sensitivity over traditional viral culture methods and to have a sensitivity comparable to those of individual real-time nucleic acid tests for respiratory viruses. The objective of this retrospective study was to test a new, streamlined version of this assay, the RVP Fast assay, which requires considerably less run time and operator involvement. The study compared the performance of the RVP Fast assay with those of viral culture, a direct fluorescent assay (DFA), and a panel of single and multiplex real-time PCRs in the testing of 286 respiratory specimens submitted to the Edinburgh Specialist Virology Centre for routine diagnosis of viral infection between December 2007 and February 2009. At least one respiratory viral infection was detected in 13.6% of specimens by culture and DFA combined, in 49.7% by real-time PCR, and in 46.2% by the RVP Fast assay. The sensitivity and specificity of the RVP Fast assay compared to the results of real-time PCR as the gold standard were 78.8% and 99.6%, respectively. Real-time PCR-positive specimens missed by the RVP Fast assay generally had low viral loads or were positive for adenovirus. Additionally, a small number of specimens were positive by the RVP Fast assay but were not detected by real-time PCR. For some viral targets, only a small number of positive results were found in our sample set using either method; therefore, the sensitivity of detection of the RVP Fast assay for individual targets could be investigated further with a greater number of virus-positive specimens.",,"['Gadsby, Naomi J.', 'Hardie, Alison', 'Claas, Eric C. J.', 'Templeton, Kate E.']",,,,
,PMC,Conformational Changes in the Capsid of a Calicivirus upon Interaction with Its Functional Receptor,http://dx.doi.org/10.1128/JVI.02371-09,PMC2876613,,,"Nonenveloped viral capsids are metastable structures that undergo conformational changes during virus entry that lead to interactions of the capsid or capsid fragments with the cell membrane. For members of the Caliciviridae, neither the nature of these structural changes in the capsid nor the factor(s) responsible for inducing these changes is known. Feline junctional adhesion molecule A (fJAM-A) mediates the attachment and infectious viral entry of feline calicivirus (FCV). Here, we show that the infectivity of some FCV isolates is neutralized following incubation with the soluble receptor at 37°C. We used this property to select mutants resistant to preincubation with the soluble receptor. We isolated and sequenced 24 soluble receptor-resistant (srr) mutants and characterized the growth properties and receptor-binding activities of eight mutants. The location of the mutations within the capsid structure of FCV was mapped using a new 3.6-Å structure of native FCV. The srr mutations mapped to the surface of the P2 domain were buried at the protruding domain dimer interface or were present in inaccessible regions of the capsid protein. Coupled with data showing that both the parental FCV and the srr mutants underwent increases in hydrophobicity upon incubation with the soluble receptor at 37°C, these findings indicate that FCV likely undergoes conformational change upon interaction with its receptor. Changes in FCV capsid conformation following its interaction with fJAM-A may be important for subsequent interactions of the capsid with cellular membranes, membrane penetration, and genome delivery.",,"['Ossiboff, Robert J.', 'Zhou, Yi', 'Lightfoot, Patrick J.', 'Prasad, B. V. Venkataram', 'Parker, John S. L.']",,,,
,PMC,Murine Coronavirus Delays Expression of a Subset of Interferon-Stimulated Genes,http://dx.doi.org/10.1128/JVI.00211-10,PMC2876584,,,"The importance of the type I interferon (IFN-I) system in limiting coronavirus replication and dissemination has been unequivocally demonstrated by rapid lethality following infection of mice lacking the alpha/beta IFN (IFN-α/β) receptor with mouse hepatitis virus (MHV), a murine coronavirus. Interestingly, MHV has a cell-type-dependent ability to resist the antiviral effects of IFN-α/β. In primary bone-marrow-derived macrophages and mouse embryonic fibroblasts, MHV replication was significantly reduced by the IFN-α/β-induced antiviral state, whereas IFN treatment of cell lines (L2 and 293T) has only minor effects on replication (K. M. Rose and S. R. Weiss, Viruses 1:689-712, 2009). Replication of other RNA viruses, including Theiler's murine encephalitis virus (TMEV), vesicular stomatitis virus (VSV), Sindbis virus, Newcastle disease virus (NDV), and Sendai virus (SeV), was significantly inhibited in L2 cells treated with IFN-α/β, and MHV had the ability to rescue only SeV replication. We present evidence that MHV infection can delay interferon-stimulated gene (ISG) induction mediated by both SeV and IFN-β but only when MHV infection precedes SeV or IFN-β exposure. Curiously, we observed no block in the well-defined IFN-β signaling pathway that leads to STAT1-STAT2 phosphorylation and translocation to the nucleus in cultures infected with MHV. This observation suggests that MHV must inhibit an alternative IFN-induced pathway that is essential for early induction of ISGs. The ability of MHV to delay SeV-mediated ISG production may partially involve limiting the ability of IFN regulatory factor 3 (IRF-3) to function as a transcription factor. Transcription from an IRF-3-responsive promoter was partially inhibited by MHV; however, IRF-3 was transported to the nucleus and bound DNA in MHV-infected cells superinfected with SeV.",,"['Rose, Kristine M.', 'Elliott, Ruth', 'Martínez-Sobrido, Luis', 'García-Sastre, Adolfo', 'Weiss, Susan R.']",,,,
,PMC,Development and Evaluation of Loop-Mediated Isothermal Amplification Assay for Rapid and Inexpensive Detection of Cytomegalovirus DNA in Vitreous Specimens from Suspected Cases of Viral Retinitis,http://dx.doi.org/10.1128/JCM.02248-09,PMC2884485,,,"A loop-mediated isothermal amplification (LAMP) assay for the rapid detection of cytomegalovirus (CMV) was developed and evaluated. The LAMP assay specifically amplified only CMV DNA, and no cross-reactivity with the DNA of herpes simplex virus type 1, varicella-zoster virus, adenovirus, Aspergillus flavus, or Staphylococcus aureus was observed. The sequences of the LAMP assay-positive CMV products were perfectly (100%) matched with the CMV sequence deposited in the GenBank database. The sensitivity of the LAMP assay was found to be 10 copies/μl of CMV DNA. Vitreous samples from 40 patients with suspected retinitis were subjected to LAMP and real-time PCR for the detection of CMV. Of 40 patients with suspected viral retinitis, 10 tested positive for CMV by the real-time PCR and LAMP assays. A 100% concordance was observed between the results of the two methods. The LAMP assay is a rapid, highly specific, and sensitive method for the diagnosis of retinitis caused by CMV.",,"['Reddy, Ashok Kumar', 'Balne, Praveen Kumar', 'Reddy, Rajeev Kumar', 'Mathai, Annie', 'Kaur, Inderjeet']",,,,
,PMC,Hydroxylated Sclerosporin Derivatives from the Marine-derived Fungus Cadophora malorum,http://dx.doi.org/10.1021/np900608d,PMC2846207,,,"The marine-derived fungus Cadophora malorum was isolated from the green alga Enteromorpha sp. Growth on a biomalt medium supplemented with sea salt yielded an extract from which we have isolated sclerosporin and four new hydroxylated sclerosporin derivatives, namely 15-hydroxysclerosporin (2), 12-hydroxysclerosporin (3), 11-hydroxysclerosporin (4) and 8-hydroxysclerosporin (5). The compounds were evaluated in various biological activity assays. Compound 5 showed a weak fat-accumulation inhibitory activity against 3T3-L1 murine adipocytes.",,"['Almeida, Celso', 'Eguereva, Ekaterina', 'Kehraus, Stefan', 'Siering, Carsten', 'König, Gabriele M.']",,,,
,PMC,Human Pregnancy Specific Beta-1-Glycoprotein 1 (PSG1) Has a Potential Role in Placental Vascular Morphogenesis,http://dx.doi.org/10.1095/biolreprod.109.082412,PMC2888962,,,"Previous studies suggest that human pregnancy specific beta-1-glycoproteins (PSGs) play immunomodulatory roles during pregnancy; however, other possible functions of PSGs have yet to be explored. We have observed that PSGs induce transforming growth factor beta 1 (TGFB1), which among its other diverse functions inhibits T-cell function and has proangiogenic properties. The present study investigates a potential role for PSG1, the most abundant PSG in maternal serum, as a possible inducer of proangiogenic growth factors known to play an important role in establishment of the vasculature at the maternal-fetal interface. To this end, we measured TGFB1, vascular endothelial growth factors (VEGFs) A and C, and placental growth factor (PGF) protein levels in several cell types after PSG1 treatment. In addition, tube formation and wound healing assays were performed to investigate a possible direct interaction between PSG1 and endothelial cells. PSG1 induced up-regulation of both TGFB1 and VEGFA in human monocytes, macrophages, and two human extravillous trophoblast cell lines. We did not observe induction of VEGFC or PGF by PSG1 in any of the cells tested. PSG1 treatment resulted in endothelial tube formation in the presence and absence of VEGFA. Site-directed mutagenesis was performed to map the essential regions within the N-domain of PSG1 required for functional activity. We found that the aspartic acid at position 95, previously believed to be required for binding of PSGs to cells, is not required for PSG1 activity but that the amino acids implicated in the formation of a salt bridge within the N-domain are essential for PSG1 function.",,"['Ha, Cam T.', 'Wu, Julie A.', 'Irmak, Ster', 'Lisboa, Felipe A.', 'Dizon, Anne M.', 'Warren, James W.', 'Ergun, Suleyman', 'Dveksler, Gabriela S.']",,,,
,PMC,Human Picobirnaviruses Identified by Molecular Screening of Diarrhea Samples,http://dx.doi.org/10.1128/JCM.02452-09,PMC2863890,,,"The global threat of (re)emerging infectious viruses requires a more effective approach regarding virus surveillance and diagnostic assays, as current diagnostics are often virus species specific and not able to detect highly divergent or unknown viruses. A systematic exploration of viruses that infect humans is the key to effectively counter the potential public health threat caused by new and emerging infectious diseases. The human gut is a known reservoir of a wide variety of microorganisms, including viruses. In this study, Dutch clinical diarrhea samples for which no etiological agent could be identified by available cell culture, serological, or nucleic acid-based tests were gathered. Large-scale molecular RNA virus screening based on host nucleic acid depletion, sequence-independent amplification, and sequencing of partially purified viral RNA from a limited number of clinical diarrhea samples revealed four eukaryotic virus species. Among the detected viruses were a rhinovirus and a new picobirnavirus variant. In total, ∼20% of clinical diarrhea samples contained human picobirnavirus sequences. The Dutch picobirnaviruses belonged to different phylogenetic clades and did not group with other picobirnaviruses according to year of isolation or host species. Interestingly, the average age of patients infected with picobirnavirus was significantly higher than that of uninfected patients. Our data show that sequence-independent amplification of partially purified viral RNA is an efficient procedure for identification of known and highly divergent new RNA viruses in clinical diarrhea samples.",,"['van Leeuwen, Marije', 'Williams, Marisol M. W.', 'Koraka, Penelope', 'Simon, James H.', 'Smits, Saskia L.', 'Osterhaus, Albert D. M. E.']",,,,
,PMC,Lambda Interferon Renders Epithelial Cells of the Respiratory and Gastrointestinal Tracts Resistant to Viral Infections,http://dx.doi.org/10.1128/JVI.00272-10,PMC2876583,,,"Virus-infected cells secrete a broad range of interferons (IFN) which confer resistance to yet uninfected cells by triggering the synthesis of antiviral factors. The relative contributions of the various IFN subtypes to innate immunity against virus infections remain elusive. IFN-α, IFN-β, and other type I IFN molecules signal through a common, universally expressed cell surface receptor, whereas type III IFN (IFN-λ) uses a distinct cell-type-specific receptor complex for signaling. Using mice lacking functional receptors for type I IFN, type III IFN, or both, we found that IFN-λ plays an important role in the defense against several human pathogens that infect the respiratory tract, such as influenza A virus, influenza B virus, respiratory syncytial virus, human metapneumovirus, and severe acute respiratory syndrome (SARS) coronavirus. These viruses were more pathogenic and replicated to higher titers in the lungs of mice lacking both IFN receptors than in mice with single IFN receptor defects. In contrast, Lassa fever virus, which infects via the respiratory tract but primarily replicates in the liver, was not influenced by the IFN-λ receptor defect. Careful analysis revealed that expression of functional IFN-λ receptor complexes in the lung and intestinal tract is restricted to epithelial cells and a few other, undefined cell types. Interestingly, we found that SARS coronavirus was present in feces from infected mice lacking receptors for both type I and type III IFN but not in those from mice lacking single receptors, supporting the view that IFN-λ contributes to the control of viral infections in epithelial cells of both respiratory and gastrointestinal tracts.",,"['Mordstein, Markus', 'Neugebauer, Eva', 'Ditt, Vanessa', 'Jessen, Birthe', 'Rieger, Toni', 'Falcone, Valeria', 'Sorgeloos, Frederic', 'Ehl, Stephan', 'Mayer, Daniel', 'Kochs, Georg', 'Schwemmle, Martin', 'Günther, Stephan', 'Drosten, Christian', 'Michiels, Thomas', 'Staeheli, Peter']",,,,
,PMC,The continuing barriers to research in China,http://dx.doi.org/10.1503/cmaj.100035,PMC2842863,,,,,"Tang, Jin-Ling",,,,
,PMC,"Bluetongue virus coat protein VP2 contains sialic acid-binding domains, and VP5 resembles enveloped virus fusion proteins",http://dx.doi.org/10.1073/pnas.0913403107,PMC2852009,,,"Bluetongue virus (BTV) is transmitted by blood-feeding insects (Culicoides sp.) and causes hemorrhagic diseases in livestock. BTV is a nonenveloped, double-stranded RNA (dsRNA) virus with two capsids: a well-studied, stable core enclosing the dsRNA genome and a highly unstable, poorly studied coat responsible for host cell attachment and entry. Here, based on cryo-electron microscopy (cryoEM), we report a 7-Å resolution structure of the infectious BTV virion, including the coat proteins. We show that unlike other dsRNA viruses, the VP2 attachment trimer has a triskelion shape composed of three tip domains branching from a central hub domain. We identify three putative sialic acid-binding pockets in the hub and present supporting biochemical data indicating sugar moiety binding is important for BTV infection. Despite being a nonenveloped virus, the putative VP5 membrane penetration trimer, located slightly inward of the VP2 attachment trimer, has a central coiled-coil α-helical bundle, similar to the fusion proteins of many enveloped viruses (e.g., HIV, herpesviruses, vesicular stomatitis virus, and influenza virus). Moreover, mapping of the amino acid sequence of VP5 to the secondary structural elements identified by cryoEM locates 15 amphipathic α-helical regions on the external surface of each VP5 trimer. The cryoEM density map also reveals few, weak interactions between the VP5 trimer and both the outer-coat VP2 trimer and the underlying core VP7 trimer, suggesting that the surface of VP5 could unfurl like an umbrella during penetration and shedding of the coat to release the transcriptionally active core particle.",,"['Zhang, Xing', 'Boyce, Mark', 'Bhattacharya, Bishnupriya', 'Zhang, Xiaokang', 'Schein, Stan', 'Roy, Polly', 'Zhou, Z. Hong']",,,,
,PMC,Modeling host responses in ferrets during A/California/07/2009 influenza infection,http://dx.doi.org/10.1016/j.virol.2010.02.020,PMC2862141,,,"Immune responses during infection with pandemic H1N1 2009 influenza A virus (2009-H1N1) are still poorly understood. Using an experimental infection model in ferrets, we examined the pathological features and characterized the host immune responses by using microarray analysis, during infection with 2009-H1N1 A/California/07/2009 and seasonal A/Brisbane/59/2007. Chemokines CCL2, CCL8, CXCL7 and CXCL10 along with the majority of interferon-stimulated genes were expressed early, correlated to lung pathology, and abruptly decreased expression on day 7 following infection of A/California/07/2009. Interestingly, the drop in innate immune gene expression was replaced by a significant increase of the adaptive immune genes for granzymes and immunoglobulins. Serum anti-influenza antibodies were first observed on day 7, commensurate with the viral clearance. We propose that lung pathology in humans occurs during the innate phase of host immunity and a delay or failure to switch to the adaptive phase may contribute to morbidity and mortality during severe 2009-H1N1 infections.",,"['Rowe, Thomas', 'León, Alberto J.', 'Crevar, Corey J.', 'Carter, Donald M.', 'Xu, Luoling', 'Ran, Longsi', 'Fang, Yuan', 'Cameron, Cheryl M.', 'Cameron, Mark J.', 'Banner, David', 'Ng, Derek CK', 'Ran, Ran', 'Weirback, Heather K.', 'Wiley, Clayton A.', 'Kelvin, David J.', 'Ross, Ted M.']",,,,
,PMC,Mucosally delivered peptides prime strong immunity in HLA-A2.1 transgenic rabbits,http://dx.doi.org/10.1016/j.vaccine.2010.03.015,PMC2879011,,,"DNA vaccines delivered subcutaneously by gene-gun have generated strong protective and therapeutic immunity in rabbits. Recent studies have shown that peptides delivered by the mucosal routes also stimulate local and systemic immune responses. Since mucosal delivery is easier to administer and more cost-effective when compared to gene-gun delivery, we were interested to learn whether mucosally-delivered peptides would prime protective immunity comparable to that of gene-gun delivered DNA in rabbits. Our newly developed HLA-A2.1 transgenic rabbit model was used to test the hypothesis. We chose an HLA-A2.1 restricted cottontail rabbit papillomavirus (CRPV) E1 epitope (E1/303–311, MLQEKPFQL) for the peptide immunization studies because it provided complete protection when used as a DNA vaccine. Adjuvant has been widely used to boost immunity for vaccines. In this study, three adjuvants reported to be effective for rabbits (TT helper motif, PADRE and CpG2007) were tested with the peptide vaccine. Peptide alone or fused to TT helper or PADRE to create chimeric peptides was delivered by two mucosal routes (ocular and intranasal) together. Partial protection was found in HLA-A2.1 transgenic rabbits when peptide was delivered mucosally in the presence of adjuvant. When a subsequent booster of a half dose of the corresponding DNA vaccine was delivered, complete protections were achieved. We conclude that mucosal peptide immunization can be combined with a single DNA vaccination to provide strong protective immunity in rabbits.",,"['Hu, Jiafen', 'Cladel, Nancy', 'Balogh, Karla', 'Christensen, Neil']",,,,
,PMC,Antibody-mediated Neutralization of Ebola Virus Can Occur by Two Distinct Mechanisms,http://dx.doi.org/10.1016/j.virol.2010.02.029,PMC3351102,,,"Human Ebola virus (EBOV) causes severe hemorrhagic fever disease with high mortality and there is no vaccine or treatment. Antibodies in survivors occur early, are sustained, and can delay infection when transferred into nonhuman primates. Monoclonal antibodies (mAbs) from survivors exhibit potent neutralizing activity in vitro and are protective in rodents. To better understand targets and mechanisms of neutralization, we investigated a panel of mAbs shown previously to react with the envelope glycoprotein (GP). While one non-neutralizing mAb recognized a GP epitope in the non-essential mucin-like domain, the rest were specific for GP1, were neutralizing, and could be further distinguished by reactivity with secreted GP. We show that survivor antibodies, human KZ52 and monkey JP3K11, were specific for conformation-dependent epitopes comprising residues in GP1 and GP2 and that neutralization occurred by two distinct mechanisms; KZ52 inhibited cathepsin cleavage of GP whereas JP3K11 recognized the cleaved, fusion-active form of GP.",,"['Shedlock, Devon J.', 'Bailey, Michael A.', 'Popernack, Paul M.', 'Cunningham, James M.', 'Burton, Dennis R.', 'Sullivan, Nancy J.']",,,,
,PMC,FAO‐OIE‐WHO Joint Technical Consultation on Avian Influenza at the Human‐Animal Interface,http://dx.doi.org/10.1111/j.1750-2659.2009.00114.x,PMC6503741,,,"Please cite this paper as: Writing Committee for the Joint Technical Consultation on Avian Influenza at the Human‐Animal Interface. FAO‐OIE‐WHO Joint Technical Consultation on Avian Influenza at the Human‐Animal Interface. 7–9 October, 2008, Verona, Italy. Consultation Summary, May 2010. Influenza and Other Respiratory Viruses. 4 (Suppl. 1): 1–29. For the past 10 years, animal health experts and human health experts have been gaining experience in the technical aspects of avian influenza in mostly separate fora. More recently, in 2006, in a meeting of the small WHO Working Group on Influenza Research at the Human Animal Interface (Meeting report available from: http://www.who.int/csr/resources/publications/influenza/WHO_CDS_EPR_GIP_2006_3/en/index.html) in Geneva allowed influenza experts from the animal and public health sectors to discuss together the most recent avian influenza research. Ad hoc bilateral discussions on specific technical issues as well as formal meetings such as the Technical Meeting on HPAI and Human H5N1 Infection (Rome, June, 2007; information available from: http://www.fao.org/avianflu/en/conferences/june2007/index.html) have increasingly brought the sectors together and broadened the understanding of the topics of concern to each sector. The sectors have also recently come together at the broad global level, and have developed a joint strategy document for working together on zoonotic diseases (Joint strategy available from: ftp://ftp.fao.org/docrep/fao/011/ajl37e/ajl37e00.pdf). The 2008 FAO‐OIE‐WHO Joint Technical Consultation on Avian Influenza at the Human Animal Interface described here was the first opportunity for a large group of influenza experts from the animal and public health sectors to gather and discuss purely technical topics of joint interest that exist at the human‐animal interface. During the consultation, three influenza‐specific sessions aimed to (1) identify virological characteristics of avian influenza viruses (AIVs) important for zoonotic and pandemic disease, (2) evaluate the factors affecting evolution and emergence of a pandemic influenza strain and identify existing monitoring systems, and (3) identify modes of transmission and exposure sources for human zoonotic influenza infection (including discussion of specific exposure risks by affected countries). A final session was held to discuss broadening the use of tools and systems to other emerging zoonotic diseases. The meeting was structured as short technical presentations with substantial time available for facilitated discussion, to take advantage of the vast influenza knowledge and experience available from the invited expert participants. Particularly important was the identification of gaps in knowledge that have not yet been filled by either sector. Technical discussions focused on H5N1, but included other potentially zoonotic avian and animal influenza viruses whenever possible. During the consultation, the significant threat posed by subtypes other than H5N1 was continually emphasized in a variety of contexts. It was stressed that epidemiological and virological surveillance for these other viruses should be broadening and strengthened. The important role of live bird markets (LBMs) in amplifying and sustaining AIVs in some countries was also a recurring topic, and the need for better understanding of the role of LBMs in human zoonotic exposure and infection was noted. Much is understood about the contribution of various virus mutations and gene combinations to transmissibility, infectivity, and pathogenicity, although it was agreed that the specific constellation of gene types and mutations that would characterize a potentially pandemic virus remains unclear. The question of why only certain humans have become infected with H5N1 in the face of massive exposure in some communities was frequently raised during discussion of human exposure risks. It was suggested that individual‐level factors may play a role. More research is needed to address this as well as questions of mode of transmission, behaviors associated with increased risk, virological and ecological aspects, and viral persistence in the environment in order to better elucidate specific human exposure risks. It became clear that great strides have been made in recent years in collaboration between the animal health and public health sectors, especially at the global level. In some countries outbreaks of H5N1 are being investigated jointly. Even greater transparency, cooperation, and information and materials exchange would allow more timely and effective responses in emergency situations, as well as in assessment and planning phases. Ensuring sustainability was also frequently emphasized, e.g. in infrastructure and capacity development and in development of tools and systems for surveillance, assessment and response. It was suggested that one way for tools and systems built or planned to address avian influenza to become more sustainable would be to make them applicable for a broader array of existing and emerging zoonotic diseases.",,,,,,
,PMC,Phages Harboring Specific Peptides That Recognize the N Protein of the Porcine Reproductive and Respiratory Syndrome Virus Distinguish the Virus from Other Viruses,http://dx.doi.org/10.1128/JCM.01707-09,PMC2863871,,,"The aim of the current study was to develop a novel diagnostic test for detecting porcine reproductive and respiratory syndrome virus (PRRSV) using phage display technology. The N gene of PRRSV isolate HH08 was cloned following reverse transcription-PCR. Sequence comparison indicated that the N gene shared 96.4% homology to that of North American PRRSV (isolate VR2332) and 35.5% with that of European PRRSV (isolate LV), indicating that the PRRSV isolate was related to the North American PRRSV genotype. The bacterially expressed N protein was used as a target in a biopanning process using a phage display random peptide library. Seven phages expressing different peptides had a specific binding activity with the N protein. The putative binding motifs were identified by DNA sequencing. More importantly, the selected phages harboring specific peptides that recognize the N protein of PRRSV were able to efficiently distinguish PRRSV from other viruses in enzyme-linked immunosorbent assays.",,"['Ren, Xiaofeng', 'Wang, Mingcui', 'Yin, Jiechao', 'Li, Guangxing']",,,,
,PMC,Engineering RNA for Targeted siRNA Delivery and Medical Application,http://dx.doi.org/10.1016/j.addr.2010.03.008,PMC2906696,,,"RNA engineering for nanotechnology and medical applications is an exciting emerging research field. RNA has intrinsically defined features on the nanometer scale and is a particularly interesting candidate for such applications due to its amazing diversity, flexibility and versatility in structure and function. Specifically, the current use of siRNA to silence target genes involved in disease has generated much excitement in the scientific community. The intrinsic ability to sequence-specifically down-regulate gene expression in a temporally- and spatially-controlled fashion has led to heightened interest and rapid development of siRNA-based therapeutics. Though methods for gene silencing with high efficacy and specificity have been achieved in vitro, the effective delivery of nucleic acids to specific cells in vivo has been a hurdle for RNA therapeutics. This review covers different RNA-based approaches for diagnosis, prevention and treatment of human disease, with a focus on the latest developments of nonviral carriers of siRNA for delivery in vivo. The applications and challenges of siRNA therapy, as well as potential solutions to these problems, the approaches for using phi29 pRNA-based vectors as polyvalent vehicles for specific delivery of siRNA, ribozymes, drugs or other therapeutic agents to specific cells for therapy will also be addressed.",,"['Guo, Peixuan', 'Coban, Oana', 'Snead, Nick', 'Trebley, Joe', 'Hoeprich, Steve', 'Guo, Songchuan', 'Shu, Yi']",,,,
,PMC,Escape from Human Monoclonal Antibody Neutralization Affects In Vitro and In Vivo Fitness of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1086/651022,PMC2826557,,,"BACKGROUND: Severe Acute Respiratory Syndrome (SARS) emerged as a human disease in 2002 and detailed phylogenetic analysis and epidemiological studies have suggested that the SARS-Coronavirus (SARS-CoV) originated from animals. The Spike (S) glycoprotein has been identified as a major target of protective immunity and contains at least three regions that are targeted by neutralizing antibodies in the S1 and S2 domains. We previously characterized a panel of neutralizing human monoclonal antibodies (MAbs) but the majority of epitopes recognized by the MAbs remained unknown. METHODS: In this study we generated neutralization escape mutants and studied the effect of these neutralization escape mutations on human and animal receptor usage as well as in vitro and in vivo fitness. RESULTS: Distinct but partially overlapping sets of amino acids were identified that are critical to the binding of MAbs with differential neutralization profiles. We also identified possible interactions between the S1 and S2 domains of the SARS-CoV S glycoprotein. Finally, we showed that escape from neutralization usually attenuates SARS-CoV infection. CONCLUSIONS: These data provide a mechanism to overcome neutralization escape by using broadly cross reactive cocktails of cross-neutralizing MAbs that recognize residues within the receptor binding domain, critical for virus replication and virulence.",,"['Rockx, Barry', 'Donaldson, Eric', 'Frieman, Matthew', 'Sheahan, Timothy', 'Corti, Davide', 'Lanzavecchia, Antonio', 'Baric, Ralph S.']",,,,
,PMC,Effects of Air Temperature and Relative Humidity on Coronavirus Survival on Surfaces,http://dx.doi.org/10.1128/AEM.02291-09,PMC2863430,,,"Assessment of the risks posed by severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) on surfaces requires data on survival of this virus on environmental surfaces and on how survival is affected by environmental variables, such as air temperature (AT) and relative humidity (RH). The use of surrogate viruses has the potential to overcome the challenges of working with SARS-CoV and to increase the available data on coronavirus survival on surfaces. Two potential surrogates were evaluated in this study; transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) were used to determine effects of AT and RH on the survival of coronaviruses on stainless steel. At 4°C, infectious virus persisted for as long as 28 days, and the lowest level of inactivation occurred at 20% RH. Inactivation was more rapid at 20°C than at 4°C at all humidity levels; the viruses persisted for 5 to 28 days, and the slowest inactivation occurred at low RH. Both viruses were inactivated more rapidly at 40°C than at 20°C. The relationship between inactivation and RH was not monotonic, and there was greater survival or a greater protective effect at low RH (20%) and high RH (80%) than at moderate RH (50%). There was also evidence of an interaction between AT and RH. The results show that when high numbers of viruses are deposited, TGEV and MHV may survive for days on surfaces at ATs and RHs typical of indoor environments. TGEV and MHV could serve as conservative surrogates for modeling exposure, the risk of transmission, and control measures for pathogenic enveloped viruses, such as SARS-CoV and influenza virus, on health care surfaces.",,"['Casanova, Lisa M.', 'Jeon, Soyoung', 'Rutala, William A.', 'Weber, David J.', 'Sobsey, Mark D.']",,,,
,PMC,Clinical trials with oncolytic reovirus: Moving beyond phase I into combinations with standard therapeutics,http://dx.doi.org/10.1016/j.cytogfr.2010.02.006,PMC3915505,,,"It is time for those working on oncolytic viruses to take stock of the status of the field. We now have at our disposal an array of potential therapeutic agents, and are beginning to conduct early-phase clinical trials in patients with relapsed/metastatic cancers. By drawing on lessons learned during the development of other biological therapies, such as monoclonal antibodies and targeted small molecule inhibitors, we are now in a position to chart the course of the next wave of trials that will go beyond the phase I studies of safety and feasibility. In this article we review our approach to the development of oncolytic viruses as cancer therapeutics. In doing so, we emphasise the fact that this process is modular and involves multiple iterative steps between the laboratory and the clinic. Ultimately, at least in the medium term, the future of oncolytic virotherapy lies in combination regimens with standard anti-cancer agents such as radiation and chemotherapy.",,"['Harrington, K.J.', 'Vile, R.G.', 'Melcher, A.', 'Chester, J.', 'Pandha, H.S.']",,,,
,PMC,Human rhinovirus and coronavirus detection among allogeneic hematopoietic stem cell transplantation recipients,http://dx.doi.org/10.1182/blood-2009-09-244152,PMC2837322,,,"Little is known about clinical and virologic manifestations of rhinovirus (HRV) and coronavirus (HCoV) infections after hematopoietic cell transplantation (HCT). We performed surveillance for 1 year and describe the natural history of these infections during the first 100 days after allogeneic HCT, when symptom surveys and upper respiratory samples were collected weekly. Samples were tested using RT-PCR for HRVs and HCoVs (OC43, 229E, HKU1, and NL63). Among 215 patients, 64 (30%) patients had 67 infections. Day 100 cumulative incidence estimate was 22.3% for HRV and 11.1% for HCoV. Median duration of viral shedding was 3 weeks; prolonged shedding of at least 3 months occurred in 6 of 45 patients with HRV and 3 of 22 with HCoV. Six patients with HRV and 9 with HCoV were asymptomatic. HRV infection was associated with rhinorrhea, congestion, postnasal drip, sputum, and cough; HCoV infection was not associated with respiratory symptoms or hepatic dysfunction. Lower respiratory infection developed in 2 patients with HRV before day 100, and 1 each with HRV and HCoV after day 100. HRV and HCoV infections are common in the first 100 days after HCT, viral shedding lasts more than 3 weeks in half, and lower respiratory infection is rare.",,"['Milano, Filippo', 'Campbell, Angela P.', 'Guthrie, Katherine A.', 'Kuypers, Jane', 'Englund, Janet A.', 'Corey, Lawrence', 'Boeckh, Michael']",,,,
,PMC,RNA-cleaving properties of human apurinic/apyrimidinic endonuclease 1 (APE1),,PMC3180037,,,"We have recently identified apurinic/apyrimidinic endonuclease 1 (APE1) as an endoribonuclease that cleaves c-myc mRNA in vitro and regulates c-myc mRNA levels and half-life in cells. This study was undertaken to further unravel the RNA-cleaving properties of APE1. Here, we show that APE1 cleaves RNA in the absence of divalent metal ions and, at 2 mM, Zn(2+), Ni(2+), Cu(2+), or Co(2+) inhibited the endoribonuclease activity of APE1. APE1 is able to cleave CD44 mRNA, microRNAs (miR-21, miR-10b), and three RNA components of SARS-corona virus (orf1b, orf3, spike) suggesting that, when challenged, it can cleave any RNAs in vitro. APE1 does not cleave strong doublestranded regions of RNA and it has a strong preference for 3’ of pyrimidine, especially towards UA, CA, and UG sites at single-stranded or weakly paired regions. It also cleaves RNA weakly at UC, CU, AC, and AU sites in single-stranded or weakly paired regions. Finally, we found that APE1 can reduce the ability of the Dicer enzyme to process premiRNAs in vitro. Overall, this study has revealed some previously unknown biochemical properties of APE1 which has implications for its role in vivo.",,"['Kim, Wan-Cheol', 'King, Dustin', 'Lee, Chow H.']",,,,
,PMC,Development and Preliminary Evaluation of a Rapid Oligochromatographic Assay for Specific Detection of New Human Influenza A H1N1 Virus,http://dx.doi.org/10.1128/JCM.01487-09,PMC2863916,,,"A new oligochromatographic assay, Speed-Oligo Novel Influenza A H1N1, was designed and optimized for the specific detection of the 2009 influenza A H1N1 virus. The assay is based on a PCR method coupled to detection of PCR products by means of a dipstick device. The target sequence is a 103-bp fragment within the hemagglutinin gene. The analytical sensitivity of the new assay was measured with serial dilutions of a plasmid that contained the target sequence, and we determined that down to one copy per reaction of the plasmid was reliably detected. Diagnostic performance was assessed with 103 RNAs from suspected cases (40 positive and 63 negative results) previously analyzed with a reference real-time PCR technique. All positive cases were confirmed, and no false-positive results were detected with the new assay. No cross-reactions were observed when other viral strains or clinical samples with other respiratory viruses were tested. According to these results, this new assay has 100% sensitivity and specificity. The turnaround time for the whole procedure was 140 min. The assay may be especially useful for the specific detection of 2009 H1N1 virus in laboratories not equipped with real-time PCR instruments.",,"['Pérez-Ruiz, Mercedes', 'Navarro-Marí, José-María', 'Bautista-Marín, María-Fé', 'Pedrosa-Corral, Irene', 'Sanbonmatsu-Gámez, Sara', 'Camacho, Ana G.', 'Rojas, José', 'Ruiz-Ortiz, Jorge', 'Rodríguez-Granger, Javier', 'Carrillo, José Antonio']",,,,
,PMC,Genetic and Antigenic Characterization of Newly Isolated Bovine Toroviruses from Japanese Cattle,http://dx.doi.org/10.1128/JCM.02339-09,PMC2863908,,,"Torovirus, a member of the Coronaviridae family, is a gastrointestinal infectious agent that has been identified in humans, cattle, pigs, and equines. Toroviruses, except equine torovirus, are difficult to propagate in cell culture; indeed, to date, only the Aichi/2004 strain of bovine torovirus (BToV) has been isolated among the human, bovine, and porcine toroviruses. In the present study, four cytopathogenic BToVs were isolated from diarrheal feces of the cattle using the HRT-18 cell line, and their genetic and antigenic properties were compared. The cytopathogenic features of BToV isolates in HRT-18 cells were similar to those of the Aichi/2004 strain. However, none of the isolates showed cytopathogenic effects in the HRT-18 cells of different origin, suggesting that one significant factor contributing to the cytopathogenicity of BToV depends on properties of the HRT-18 cells themselves. All BToVs isolated were able to agglutinate mouse, but not chicken, erythrocytes, while they lacked receptor-destroying enzyme activity. Analysis of the N terminus of the spike gene showed that three isolates, but not the Gifu-2007TI/E strain, were phylogenetically located in cluster 1 and its analogs and revealed high cross-reactivity with each other, as demonstrated by neutralization (NT) and hemagglutination inhibition (HI) assays. The Gifu-2007TI/E strain was classified close to cluster 2 and exhibited relatively low cross-reactivity with these viruses; however, the difference was not sufficient to classify BToVs into serotypes, suggesting that at least two subtypes distinguishable by the structure of the N terminus of the spike gene and that both NT and HI tests may be exist.",,"['Ito, Toshihiro', 'Katayama, Shigeji', 'Okada, Nobutaka', 'Masubuchi, Katsuo', 'Fukuyama, Shin-ichi', 'Shimizu, Mitsugu']",,,,
,PMC,Avian Bornavirus Associated with Fatal Disease in Psittacine Birds,http://dx.doi.org/10.1128/JVI.02567-09,PMC2903261,,,"Thanks to new technologies which enable rapid and unbiased screening for viral nucleic acids in clinical specimens, an impressive number of previously unknown viruses have recently been discovered. Two research groups independently identified a novel negative-strand RNA virus, now designated avian bornavirus (ABV), in parrots with proventricular dilatation disease (PDD), a severe lymphoplasmacytic ganglioneuritis of the gastrointestinal tract of psittacine birds that is frequently accompanied by encephalomyelitis. Since its discovery, ABV has been detected worldwide in many captive parrots and in one canary with PDD. ABV induced a PDD-like disease in experimentally infected cockatiels, strongly suggesting that ABV is highly pathogenic in psittacine birds. Until the discovery of ABV, the Bornaviridae family consisted of a single species, classical Borna disease virus (BDV), which is the causative agent of a progressive neurological disorder that affects primarily horses, sheep, and some other farm animals in central Europe. Although ABV and BDV share many biological features, there exist several interesting differences, which are discussed in this review.",,"['Staeheli, Peter', 'Rinder, Monika', 'Kaspers, Bernd']",,,,
,PMC,Glycoprotein D of Bovine Herpesvirus 5 (BoHV-5) Confers an Extended Host Range to BoHV-1 but Does Not Contribute to Invasion of the Brain,http://dx.doi.org/10.1128/JVI.00228-10,PMC2876591,,,"Bovine herpesvirus 1 (BoHV-1) and BoHV-5 are closely related pathogens of cattle, but only BoHV-5 is considered a neuropathogen. We engineered intertypic gD exchange mutants with BoHV-1 and BoHV-5 backbones in order to address their in vitro and in vivo host ranges, with particular interest in invasion of the brain. The new viruses replicated in cell culture with similar dynamics and to titers comparable to those of their wild-type parents. However, gD of BoHV-5 (gD5) was able to interact with a surprisingly broad range of nectins. In vivo, gD5 provided a virulent phenotype to BoHV-1 in AR129 mice, featuring a high incidence of neurological symptoms and early onset of disease. However, only virus with the BoHV-5 backbone, independent of the gD type, was detected in the brain by immunohistology. Thus, gD of BoHV-5 confers an extended cellular host range to BoHV-1 and may be considered a virulence factor but does not contribute to the invasion of the brain.",,"['Gabev, Evgeni', 'Tobler, Kurt', 'Abril, Carlos', 'Hilbe, Monika', 'Senn, Claudia', 'Franchini, Marco', 'Campadelli-Fiume, Gabriella', 'Fraefel, Cornel', 'Ackermann, Mathias']",,,,
,PMC,Species-Specific Antagonism of Host ISGylation by the Influenza B Virus NS1 Protein,http://dx.doi.org/10.1128/JVI.02395-09,PMC2863827,,,"Interferon-stimulated expression and conjugation of the ubiquitin-like modifier ISG15 restricts replication of several viruses. Here, we established complete E1-activating, E2-conjugating, and E3 ligase-dependent expression systems for assaying both human and mouse ISGylation. We confirm that human HerC5, but not human HerC6, has ISG15 E3 ligase activity and identify mouse HerC6 as a bona fide ISG15 E3 ligase. Furthermore, we demonstrate that influenza B virus NS1 protein potently antagonizes human but not mouse ISGylation, a property dependent on B/NS1 binding the N-terminal domain of human but not mouse ISG15. Using chimeric human/mouse ISG15 constructs, we show that the B/NS1:ISG15 interaction is both necessary and sufficient to inhibit ISGylation regardless of the ligation machinery used. Inability to block ISGylation in certain species may contribute to limiting influenza B virus host range.",,"['Versteeg, Gijs A.', 'Hale, Benjamin G.', 'van Boheemen, Sander', 'Wolff, Thorsten', 'Lenschow, Deborah J.', 'García-Sastre, Adolfo']",,,,
,PMC,Different Potential of C-Type Lectin-Mediated Entry between Marburg Virus Strains,http://dx.doi.org/10.1128/JVI.02021-09,PMC2863822,,,"The glycoproteins (GPs) of filoviruses are responsible for virus entry into cells. It is known that GP interacts with cellular C-type lectins for virus attachment to cells. Since primary target cells of filoviruses express C-type lectins, C-type lectin-mediated entry is thought to be a possible determinant of virus tropism and pathogenesis. We compared the efficiency of C-type lectin-mediated entry between Marburg virus strains Angola and Musoke by using a vesicular stomatitis virus (VSV) pseudotype system. VSV pseudotyped with Angola GP (VSV-Angola) infected K562 cells expressing the C-type lectin, human macrophage galactose-type C-type lectin (hMGL), or dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) more efficiently than VSV pseudotyped with Musoke GP (VSV-Musoke). Unexpectedly, the binding affinity of the C-type lectins to the carbohydrates on GPs did not correlate with the different efficiency of C-type lectin-mediated entry. Site-directed mutagenesis identified the amino acid at position 547, which switched the efficiency of C-type lectin-mediated entry. In a three-dimensional model of GP, this amino acid was in close proximity to the putative site of cathepsin processing. Interestingly, the cathepsin inhibitors reduced the infectivity of VSV-Angola less efficiently than that of VSV-Musoke in C-type lectin-expressing K562 cells, whereas only a limited difference was found in control cells. The amino acid at position 547 was critical for the different effects of the inhibitors on the virus infectivities. These results suggest that the efficiency of C-type lectin-mediated entry of filoviruses is controlled not only by binding affinity between C-type lectins and GP but also by mechanisms underlying endosomal entry, such as proteolytic processing by the cathepsins.",,"['Matsuno, Keita', 'Kishida, Noriko', 'Usami, Katsuaki', 'Igarashi, Manabu', 'Yoshida, Reiko', 'Nakayama, Eri', 'Shimojima, Masayuki', 'Feldmann, Heinz', 'Irimura, Tatsuro', 'Kawaoka, Yoshihiro', 'Takada, Ayato']",,,,
,PMC,Autographa californica Multicapsid Nucleopolyhedrovirus Efficiently Infects Sf9 Cells and Transduces Mammalian Cells via Direct Fusion with the Plasma Membrane at Low pH,http://dx.doi.org/10.1128/JVI.02517-09,PMC2863812,,,"The budded virus (BV) of the Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) infects insect cells and transduces mammalian cells mainly through the endocytosis pathway. However, this study revealed that the treatment of the virus bound to Sf9 cells at low pH could efficiently rescue the infectivity of AcMNPV in the presence of endocytosis pathway inhibitors. A colocalization assay of the major capsid protein VP39 with the early endosome marker EEA1 showed that at low pH, AcMNPV entered Sf9 cells via an endosome-independent pathway. Using a fluorescent probe (R18), we showed that at low pH, the viral nucleocapsid entered Sf9 cells via direct fusion at the cell surface. By using the myosin-specific inhibitor 2,3-butanedione monoxime (BDM) and the microtubule inhibitor nocodazole, the low pH-triggered direct fusion was demonstrated to be dependent on myosin-like proteins and independent of microtubules. The reverse transcription-PCR of the IE1 gene as a marker for viral entry showed that the kinetics of AcMNPV in cells triggered by low pH was similar to that of the normal entry via endocytosis. The low pH-mediated infection assay and VP39 and EEA1 colocalization assay also demonstrated that AcMNPV could efficiently transduce mammalian cells via direct membrane fusion at the cell surface. More importantly, we found that a low-pH trigger could significantly improve the transduction efficiency of AcMNPV in mammalian cells, leading to the potential application of this method when using baculovirus as a vector for heterologous gene expression and for gene therapy.",,"['Dong, Sicong', 'Wang, Manli', 'Qiu, Zhijuan', 'Deng, Fei', 'Vlak, Just M.', 'Hu, Zhihong', 'Wang, Hualin']",,,,
,PMC,INFECTION – RELATED STILLBIRTHS,http://dx.doi.org/10.1016/S0140-6736(09)61712-8,PMC3893931,,,"Infection is an important cause of stillbirth world-wide; in low and middle income countries (LMICs), 50% or more are likely caused by infection. In contrast, in high income countries, only10-25% of stillbirths are caused by infection. Syphilis, where prevalent, causes the majority of infectious stillbirths and is the infection most amenable to screening and treatment. Ascending bacterial infection is a common cause of stillbirth, but prevention has proven elusive. Many viral infections are causal for stillbirth but aside from vaccination for common childhood diseases, it is unclear how most viral-caused stillbirths may be prevented. Malaria, because of its high prevalence and extensive placental damage accounts for large numbers of stillbirths. Intermittent malarial prophylaxis and insecticide impregnated bed nets should decrease stillbirths. Many animal and vector-borne infections cause stillbirth. Because this relationship is especially important in LMICs, research that more clearly defines this relationship is crucial to reduce the unacceptably high stillbirth rates in those areas.",,"['Goldenberg, Robert L.', 'McClure, Elizabeth M.', 'Saleem, Sarah', 'Reddy, Uma M.']",,,,
,PMC,Constraints within major histocompatibility complex class I restricted peptides: Presentation and consequences for T-cell recognition,http://dx.doi.org/10.1073/pnas.1000032107,PMC2851776,,,"Residues within processed protein fragments bound to major histocompatibility complex class I (MHC-I) glycoproteins have been considered to function as a series of “independent pegs” that either anchor the peptide (p) to the MHC-I and/or interact with the spectrum of αβ-T-cell receptors (TCRs) specific for the pMHC-I epitope in question. Mining of the extensive pMHC-I structural database established that many self- and viral peptides show extensive and direct interresidue interactions, an unexpected finding that has led us to the idea of “constrained” peptides. Mutational analysis of two constrained peptides (the HLA B44 restricted self-peptide (B44DPα–EEFGRAFSF) and an H2-D(b) restricted influenza peptide (D(b)PA, SSLENFRAYV) demonstrated that the conformation of the prominently exposed arginine in both peptides was governed by interactions with MHC-I-orientated flanking residues from the peptide itself. Using reverse genetics in a murine influenza model, we revealed that mutation of an MHC-I-orientated residue (SSLENFRAYV → SSLENARAYV) within the constrained PA peptide resulted in a diminished cytotoxic T lymphocyte (CTL) response and the recruitment of a limited pMHC-I specific TCR repertoire. Interactions between individual peptide positions can thus impose fine control on the conformation of pMHC-I epitopes, whereas the perturbation of such constraints can lead to a previously unappreciated mechanism of viral escape.",,"['Theodossis, Alex', 'Guillonneau, Carole', 'Welland, Andrew', 'Ely, Lauren K.', 'Clements, Craig S.', 'Williamson, Nicholas A.', 'Webb, Andrew I.', 'Wilce, Jacqueline A.', 'Mulder, Roger J.', 'Dunstone, Michelle A.', 'Doherty, Peter C.', 'McCluskey, James', 'Purcell, Anthony W.', 'Turner, Stephen J.', 'Rossjohn, Jamie']",,,,
,PMC,Regulatory T cells inhibit T cell proliferation and decrease demyelination in mice chronically infected with a coronavirus,http://dx.doi.org/10.4049/jimmunol.0903918,PMC2851486,,,"Mice infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) develop acute and chronic demyelinating diseases with histopathological similarities to MS. The process of demyelination is largely immune-mediated, as immunodeficient mice (RAG1(−/−) mice) do not develop demyelination upon infection; however, demyelination develops if these mice are reconstituted with either JHMV-immune CD4 or CD8 T cells. Since myelin destruction is a consequence of the inflammatory response associated with virus clearance, we reasoned that decreasing the amount of inflammation would diminish clinical disease and demyelination. Given that regulatory T cells (Tregs) have potent anti-inflammatory effects, we adoptively transferred Tregs into infected C57BL/6 and RAG1(−/−) mice. In both instances, transfer of Tregs decreased weight loss, clinical scores and demyelination. Transferred Tregs were not detected in the CNS of infected RAG1(−/−) mice, but rather appeared to mediate their effects in the draining cervical lymph nodes. We show that Tregs dampen the inflammatory response mediated by transferred JHMV-immune splenocytes in infected RAG1(−/−) mice by decreasing T cell proliferation, dendritic cell activation and pro-inflammatory cytokine/chemokine production, without inducing apoptosis. By extension, decreasing inflammation, whether by Treg transfer or by otherwise enhancing the anti-inflammatory milieu, could contribute to improved clinical outcomes in patients with virus-induced demyelination.",,"['Trandem, Kathryn', 'Anghelina, Daniela', 'Zhao, Jingxian', 'Perlman, Stanley']",,,,
,PMC,Analysis of Apoptosis of Memory T Cells and Dendritic Cells during the Early Stages of Viral Infection or Exposure to Toll-Like Receptor Agonists,http://dx.doi.org/10.1128/JVI.02571-09,PMC2863811,,,"Profound type I interferon (IFN-I)-dependent attrition of memory CD8 and CD4 T cells occurs early during many infections. It is dramatic at 2 to 4 days following lymphocytic choriomeningitis virus (LCMV) infection of mice and can be elicited by the IFN-inducing Toll receptor agonist poly(I:C). We show that this attrition occurs in many organs, indicating that it is due to T cell loss rather than redistribution. This loss correlated with elevated intracellular staining of T cells ex vivo for activated caspases but with only low levels of ex vivo staining with annexin V, probably due to the rapid clearance of apoptotic cells in vivo. Instead, a high frequency of annexin V-reactive CD8α(+) dendritic cells (DCs), which are known to be highly phagocytic, accumulated in the spleen as the memory T cell populations disappeared. After short in vitro incubation, memory phenotype T cells isolated from LCMV-infected mice (day 3) or mice treated with poly(I:C) (12 h) displayed substantial DNA fragmentation, as detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, compared to T cells isolated from uninfected mice, indicating a role for apoptosis in the memory T cell attrition. This apoptosis of memory CD8 T cells early during LCMV infection was reduced in mice lacking the proapoptotic molecule Bim. Evidence is presented showing that high levels of T cell attrition, as found in young mice, correlate with reduced immunodomination by cross-reactive memory cells.",,"['Bahl, Kapil', 'Hüebner, Anette', 'Davis, Roger J.', 'Welsh, Raymond M.']",,,,
,PMC,The Role Of Mitochondria In The Mammalian Antiviral Defense System,http://dx.doi.org/10.1016/j.mito.2010.02.005,PMC2874622,,,"Innate immunity is a crucial defense system against viral and bacterial pathogens, providing a rapid response to mitigate the effects of microbial attack. While more readily associated with respiration and metabolism, recent research has surprisingly identified a number of mitochondrial factors in the mammalian innate immune system. This review summarizes the novel mitochondrial proteins, such as MAVS and NLRX1, involved in this process and attempts to reconcile this new mitochondrial function with our previous knowledge of the organelle.",,"Scott, Iain",,,,
,PMC,"Immunology and Gene Therapy: Shoulder to Shoulder Into the Fray: International Symposium: Critical Frontiers Between Immunity and Gene Therapy  Pamplona, Spain, 27–28 October 2009",http://dx.doi.org/10.1038/mt.2010.7,PMC2839439,,,,,"['Smerdou, Cristian', 'Ochoa, Carmen', 'Quetglas, Jose I', 'Fontanellas, Antonio', 'Gonzalez-Aseguinolaza, Gloria', 'Vile, Richard G', 'Melero, Ignacio']",,,,
,PMC,Approaches to Increasing Surface Stress for Improving Signal-to-Noise Ratio of Microcantilever Sensors,http://dx.doi.org/10.1021/ac901955d,PMC2836585,,,"Microcantilever sensor technology has been steadily growing for the last fifteen years. While we have gained a great amount of knowledge in microcantilever bending due to surface stress changes, which is a unique property of microcantilever sensors, we are still in the early stages of understanding the fundamental surface chemistries of surface-stress-based microcantilever sensors. In general, increasing surface stress, which is caused by interactions on the microcantilever surfaces, would improve the S/N ratio, and subsequently the sensitivity and reliability of microcantilever sensors. In this review, we will summarize: A) the conditions under which a large surface stress can readily be attained, and B) the strategies to increase surface stress in case a large surface stress can not readily be reached. We will also discuss our perspectives on microcantilever sensors based on surface stress changes.",,"['Ji, Hai-Feng', 'Armon, Benjamin D.']",,,,
,PMC,Migration of Waterfowl in the East Asian Flyway and Spatial Relationship to HPAI H5N1 Outbreaks,http://dx.doi.org/10.1637/8914-043009-Reg.1,PMC4878034,,,"Poyang Lake is situated within the East Asian Flyway, a migratory corridor for waterfowl that also encompasses Guangdong Province, China, the epicenter of highly pathogenic avian influenza (HPAI) H5N1. The lake is the largest freshwater body in China and a significant congregation site for waterfowl; however, surrounding rice fields and poultry grazing have created an overlap with wild waterbirds, a situation conducive to avian influenza transmission. Reports of HPAI H5N1 in healthy wild ducks at Poyang Lake have raised concerns about the potential of resilient free-ranging birds to disseminate the virus. Yet the role wild ducks play in connecting regions of HPAI H5N1 outbreak in Asia is hindered by a lack of information about their migratory ecology. During 2007–08 we marked wild ducks at Poyang Lake with satellite transmitters to examine the location and timing of spring migration and identify any spatiotemporal relationship with HPAI H5N1 outbreaks. Species included the Eurasian wigeon (Anas penelope), northern pintail (Anas acuta), common teal (Anas crecca), falcated teal (Anas falcata), Baikal teal (Anas formosa), mallard (Anas platyrhynchos), garganey (Anas querquedula), and Chinese spotbill (Anas poecilohyncha). These wild ducks (excluding the resident mallard and Chinese spotbill ducks) followed the East Asian Flyway along the coast to breeding areas in northern China, eastern Mongolia, and eastern Russia. None migrated west toward Qinghai Lake (site of the largest wild bird epizootic), thus failing to demonstrate any migratory connection to the Central Asian Flyway. A newly developed Brownian bridge spatial analysis indicated that HPAI H5N1 outbreaks reported in the flyway were related to latitude and poultry density but not to the core migration corridor or to wetland habitats. Also, we found a temporal mismatch between timing of outbreaks and wild duck movements. These analyses depend on complete or representative reporting of outbreaks, but by documenting movements of wild waterfowl, we present ecological knowledge that better informs epidemiological investigations seeking to explain and predict the spread of avian influenza viruses.",,"['Takekawa, John Y.', 'Newman, Scott H.', 'Xiao, Xiangming', 'Prosser, Diann J.', 'Spragens, Kyle A.', 'Palm, Eric C.', 'Yan, Baoping', 'Li, Tianxian', 'Lei, Fumin', 'Zhao, Delong', 'Douglas, David C.', 'Muzaffar, Sabir Bin', 'Ji, Weitao']",,,,
,PMC,Communicable diseases in the South-East Asia Region of the World Health Organization: towards a more effective response,http://dx.doi.org/10.2471/BLT.09.065540,PMC2828785,,,"This article looks at the current burden of communicable diseases in the South-East Asia Region of the World Health Organization and analyses whether the current levels and trends in funding are adequate to meet the needs of control, prevention and treatment. Our analysis considers the Millennium Development Goals (MDGs) for health and indicators of economic progress in each country, as well as the impact of the global financial crisis on progress towards MDGs for communicable diseases in the region. The analysis indicates that the current focus of funding may need to be expanded to include less-discussed but high-burden diseases often related to inadequacies in the health sector and the particular development paths that countries pursue. Scarce funding during times of global economic recession could be used more effectively if informed by a careful analysis of the complex set of factors, including behavioural, environmental and health systems factors, that determine the burden of communicable diseases. Significant gaps in funding as well as varying regional needs warrant a more diverse set of national and international aid measures. Although regional and global collaboration is critical, the effectiveness of future policies to deal with the burden of communicable diseases in the region will only be assured if these policies are based on evidence and developed by policy-makers familiar with each country’s needs and priorities.",,"['Gupta, Indrani', 'Guin, Pradeep']",,,,
,PMC,"Vaccination of Health Care Workers for Influenza: Promote Safety Culture, Not Coercion",http://dx.doi.org/10.1007/BF03403845,PMC6974253,,,"OBJECTIVES: In British Columbia (BC), Canada, all health care facilities must have a written staff policy on influenza immunization that includes notice that non-immunized staff can be excluded from work without pay during an influenza outbreak in the facility. In light of this policy, our objectives were to explore the views of BC health care workers (HCWs) regarding how best to promote vaccine uptake. METHODS: Long-term care, and acute and community health sites in three of six health regions were divided into thirds, according to their previous season’s vaccine uptake rates, and the upper and lower thirds targeted. Ten focus groups were held. NVivo software (QSR International) and a separate editing style were used for analysis. RESULTS: Four dominant themes emerged: knowledge, communication, perceived punitive nature of workplace policy, and safety climate. HCWs across all focus groups noted that influenza campaign communications should include reinforcement of basic infection control, workplace health and healthy lifestyle choices that affect overall health. HCWs indicated that they wanted a workplace policy that is easy to understand, respectful of individual choice and not punitive. CONCLUSIONS: Our findings highlight the importance of comprehensive approaches, a message that has not appeared as strongly in previous literature. Focus group participants pointed out the importance of health and safety at work generally and felt that creating a healthy workplace culture is necessary to promoting vaccine uptake. Future vaccine promotion initiatives should be integrated into facility-wide workplace health campaigns and care taken to ensure that vaccination campaigns do not appear coercive to HCWs.",,"['Yassi, Annalee', 'Lockhart, Karen', 'Buxton, Jane A.', 'McDonald, Isobel']",,,,
,PMC,"Naturally acquired feline immunodeficiency virus (FIV) infection in cats from western Canada: Prevalence, disease associations, and survival analysis",,PMC2822370,,,"This retrospective study evaluated epidemiologic features and disease associations of feline immunodeficiency virus (FIV) infection in client owned cats from western Canada. Among 1205 cats that were tested 66 (5.5%) were positive for FIV antibody (FIV(+)) with a higher prevalence in males than females. FIV(+) cats were older than the overall population. Epidemiologic features and disease associations were compared between 58 FIV(+), but feline leukemia virus negative (FeLV(−)) cats and 58 age and sex matched FIV-negative (FIV(−)), FeLV(−) cats. FIV positivity was associated with a history of bite wounds, increasing age, and male gender. Lethargy and oral diseases were significantly associated with FIV positivity. Although several FIV(+) cats were euthanized, the survival time of FIV(+) cats after diagnosis was not significantly different from that of FIV(−) cats. In summary, FIV prevalence was low in cats from western Canada, clinical signs/diseases were mild, and lifespan was not different in FIV(+) cats.",,"['Ravi, Madhu', 'Wobeser, Gary A.', 'Taylor, Susan M.', 'Jackson, Marion L.']",,,,
,PMC,Predicting Virologic Failure in an HIV Clinic,http://dx.doi.org/10.1086/650537,PMC3101804,,,"BACKGROUND: We sought to use data captured in the electronic health record (EHR) to develop and validate a prediction rule for virologic failure in patients being treated for HIV infection. METHODS: We used EHRs at two Boston tertiary care hospitals, Massachusetts General Hospital and Brigham and Women's Hospital, to identify HIV-infected patients who were virologically suppressed (HIV RNA ≤400 copies/mL) on antiretroviral therapy between 1/1/05 and 12/31/06. We used a multivariable logistic model with data from Massachusetts General Hospital to derive a one-year virologic failure prediction rule. The model was validated using data from the Brigham and Women's Hospital. We then simplified the scoring scheme to develop a clinical prediction rule. RESULTS: The one-year virologic failure prediction model, using data from 712 Massachusetts General Hospital patients, demonstrated good discrimination (c-statistic 0.78) and calibration (χ(2) =6.6, p =0.58). The validation model, based on 362 Brigham and Women's Hospital patients, also showed good discrimination (c-statistic 0.79) and calibration (χ(2) =1.9, p =0.93). The clinical prediction rule included seven predictors, Sub-optimal Adherence, CD4 count <100/μL, Drug and/or Alcohol Abuse, Heavily ART Experienced, Missed ≥1Appointment, Prior Virologic Failure, and Suppressed ≤12 months, and appropriately stratified patients in the validation dataset into low, medium and high risk groups, with one-year virologic failure rates of 3.0%, 13.0% and 28.6%. CONCLUSIONS: A risk score based on seven variables available in the EHR predicts HIV virologic failure at one year and could be used for targeted interventions to improve outcomes in HIV disease.",,"['Robbins, Gregory K.', 'Johnson, Kristin L.', 'Chang, Yuchiao', 'Jackson, Katherine E.', 'Sax, Paul E.', 'Meigs, James B.', 'Freedberg, Kenneth A.']",,,,
,PMC,"Effects of oseltamivir treatment on duration of clinical illness and viral shedding, and household transmission of influenza virus",http://dx.doi.org/10.1086/650458,PMC2840043,,,"BACKGROUND: Large clinical trials have demonstrated the therapeutic efficacy of oseltamivir against influenza. Here we assessed its indirect effectiveness in reducing household secondary transmission in an incident cohort of influenza index cases and their household members. METHODS: We recruited index outpatients whose rapid tests for influenza were positive in 2007 and 2008. Household contacts were followed for 7–10 days during 3–4 home visits to monitor symptoms. Nose and throat swabs were collected and tested for influenza by reverse transcription polymerase chain reaction (RT-PCR) or viral culture. RESULTS: We followed 384 index cases and their household contacts. Index cases who took oseltamivir within 24 hours of symptom onset halved the time to symptom alleviation (adjusted acceleration factor (AF) 0.56; 95% CI: 0.42, 0.76). Oseltamivir treatment was not associated with statistically significant reduction in the duration of viral shedding. Household contacts of index cases who had taken oseltamivir within 24 hours of onset had a non-statistically significant lower risk of developing laboratory-confirmed infection (adjusted odds ratio (OR) 0.54; 95% CI: 0.11, 2.57) and a marginally statistically significant lower risk of clinical illness (adjusted OR 0.52; 95% CI: 0.25, 1.08) compared to contacts of index cases who did not take oseltamivir. CONCLUSIONS: Oseltamivir treatment is effective in reducing the duration of symptoms but evidence for household reduction in transmission of influenza virus was inconclusive.",,"['Ng, Sophia', 'Cowling, Benjamin J.', 'Fang, Vicky J.', 'Chan, Kwok Hung', 'Ip, Dennis K. M.', 'Cheng, Calvin K. Y.', 'Uyeki, Timothy M.', 'Houck, Peter M.', 'Malik Peiris, J. S.', 'Leung, Gabriel M.']",,,,
,PMC,The Diagnosis of Viral Respiratory Disease in Older Adults,http://dx.doi.org/10.1086/650486,PMC2826599,,,"Viral respiratory disease in older adults has been increasingly recognized as a significant cause of hospitalizations and death. Unfortunately, the recognition and diagnosis of infection due to many viral respiratory pathogens in older adults can be elusive due to atypical clinical presentations and the insensitivity of current laboratory diagnostic tests in this population. For influenza diagnosis, rapid antigen tests followed by viral culture if negative, can be useful in older adults as long as clinicians are mindful of test limitations. Although specific, rapid antigen tests are insensitive in this population. Erroneous negative results may lead to delays in timely administration of antiviral treatment and institution of appropriate isolation precautions. The increasing availability of new rapid and sensitive molecular diagnostics such as polymerase chain reaction testing, should provide more accurate and timely diagnoses of viral respiratory infections in older adults in the near future.",,"['Talbot, H. Keipp', 'Falsey, Ann R.']",,,,
,PMC,High-Throughput Binding Analysis determines the Binding Specificity of ASF/SF2 on Alternatively Spliced Human pre-mRNAs,,PMC3427726,,,"High-throughput immunoprecipitation (IP) studies of transcription factors and splicing factors have revolutionized the fields of transcription and splicing. Recent location studies on Nova1/2 and Fox2 have identified a set of cellular targets of these splicing factors. One problem with identifying binding sites for splicing factors arises from the transient role of RNA in gene expression. The primary role of most splicing factors is to bind pre-mRNA co-transcriptionally and participate in the extremely rapid process of splice site selection and catalysis. Pre-mRNA is a labile species with a steady state level that is three orders of magnitude less abundant than mRNA. As many splicing factors also bind mRNA to some degree, these substrates tend to dominate the output of location studies. Here we present an in-vitro method for screening RNA protein interactions that circumvents these problems. We screen approximately 4000 alternatively spliced exons and the entire Hepatitis C genome for binding of ASF/SF2, the only splicing factor demonstrated to function as an oncogene. From the pre-mRNA sequences returned in this screen we discovered physiologically relevant ASF recognition element motifs. ASF binds two motifs: a C-rich and a purine rich motif. Comparisons with similar data derived from the hnRNP protein PTB reveals little overlap between strong PTB and ASF/SF2 sites. We illustrate how this method could be employed to screen disease alleles with the set of small molecules that have been shown to alter splicing in search for therapies for splicing diseases.",,"['Chang, B', 'Levin, J', 'Thompson, WA', 'Fairbrother, WG']",,,,
,PMC,Pandemics: is hoping for the best enough?,http://dx.doi.org/10.1038/embor.2010.22,PMC2838697,,,"Albert Osterhaus reflects on the reasons for the increase in emerging pandemics and how we are coping with these situations. Although we might risk over-reacting, better safe than sorry is still the most reasonable policy.",,"Osterhaus, Albert D M E",,,,
,PMC,Challenges of T Cell Therapies for Virus-associated Diseases after Hematopoietic Stem Cell Transplantation,http://dx.doi.org/10.1517/14712590903456003,PMC2818535,,,"IMPORTANCE OF THE FIELD: Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many hematological malignancies and genetic disorders. A majority of patients do not have a human leukocyte antigen (HLA) identical sibling donor, and alternative stem cell sources include HLA-matched or mismatched unrelated donors and haploidentical related donors. However, alternative donor HSCT are associated with three major complications (i) graft rejection, (ii) graft-versus-host disease (GvHD) and (iii) delayed immune reconstitution leading to viral infections and relapse. AREAS COVERED IN THIS REVIEW: Graft rejection and the risk of GvHD can be significantly reduced by using intensive conditioning regimens, including in vivo T cell depletion as well as ex vivo T cell depletion of the graft. However, the benefits of removing alloreactive T cells from the graft are offset by the concomitant removal of T cells with anti-viral or anti-tumor activity as well as the profound delay in endogenous T cell recovery post-transplant. Thus, opportunistic infections, many of which are not amenable to conventional small-molecule therapeutics, are frequent in these patients and are associated with significant morbidity and high mortality rates. This review discusses current cell therapies to prevent or treat viral infections/reactivations post-transplant. WHAT THE READER WILL GAIN: The reader will gain an understanding of the current state of cell therapy to prevent and treat viral infections post-HSCT, and will be introduced to preclinical studies designed to develop and validate new manufacturing procedures intended to improve therapeutic efficacy and reduce associated toxicities. TAKE HOME MESSAGE: Reconstitution of HSCT recipients with antigen-specific T cells, produced either by allodepletion or in vitro reactivation, can offer an effective strategy to provide both immediate and long-term protection without harmful alloreactivity.",,"['Leen, Ann M.', 'Tripic, Tamara', 'Rooney, Cliona M.']",,,,
,PMC,"Unraveling the functions of plasmacytoid dendritic cells during viral infections, autoimmunity, and tolerance",http://dx.doi.org/10.1111/j.0105-2896.2009.00881.x,PMC3507434,,,"Plasmacytoid dendritic cells (pDCss) are bone marrow-derived cells that secrete large amounts of type I interferon (IFN) in response to viruses. Type I IFNs are pleiotropic cytokines with antiviral activity that also enhance innate and adaptive immune responses. Viruses trigger activation of pDCss and type I IFN responses mainly through the Toll-like receptor pathway. However, a variety of activating and inhibitory pDCs receptors fine tune the amplitude of type I IFN responses. Chronic activation and secretion of type I IFN in the absence of infection can promote autoimmune diseases. Furthermore, while activated pDCss promote immunity and autoimmunity, resting or alternatively activated pDCss may be tolerogenic. The various roles of pDCss have been extensively studied in vitro and in vivo with depleting antibodies. However, depleting antibodies cross-react with other cell types that are critical for eliciting protective immunity, potentially yielding ambiguous phenotypes. Here we discuss new approaches to assess pDCs functions in vivo and provide preliminary data on their potential roles during viral infections. Such approaches would also prove useful in the more specific evaluation of how pDCss mediate tolerance and autoimmunity. Finally, we discuss the emergent role of pDCss and one of their receptors, tetherin, in human immunodeficiency virus pathogenesis.",,"['Swiecki, Melissa', 'Colonna, Marco']",,,,
,PMC,Use of a Body Condition Score Technique to Assess Health Status in a Rat Model of Polycystic Kidney Disease,,PMC2846001,,,"Simple and noninvasive methods of assessing health and wellbeing are valuable when performing clinical evaluation of rodents used in biomedical research. Body condition score (BCS) techniques have been described for a variety of species, including mice. This method can be a sensitive objective assessment of weight loss in animal models where organ enlargement, ascites, or tumor development may mask weight loss. Although deposition of fat is similar in rats and mice, the mouse BCS technique has not been characterized in rats. Here we used the Han:SPRD rat model for polycystic kidney disease to characterize the effectiveness of the mouse BCS scale when applied to rats. This study showed a positive correlation between BCS score and renal function and a negative correlation between weight and renal function, supporting the use of BCS as an effective, noninvasive method of health assessment in this rat model. Our results also demonstrate that the BCS scale described for mice required a slight modification to capture the delay in fat deposition over the lumbar vertebrae in obese animals.",,"['Hickman, Debra L', 'Swan, Melissa']",,,,
,PMC,CT Utilization in the Prospective Diagnosis of a Case of Swine-Origin Influenza A (H1N1) Viral Infection,http://dx.doi.org/10.3941/jrcr.v4i3.427,PMC3303378,,,"The purpose of this paper is to demonstrate the potential role of CT in the early diagnosis of swine-origin influenza A (H1N1) virus (S-OIV) pneumonia. We present a case of acute influenza-like illness in which the CT findings of peribronchovascular and subpleural ground-glass opacities and consolidation resembled organizing pneumonia, and lead the radiologist to prospectively and correctly suggest the diagnosis of S-OIV infection.",,"['Ajlan, Amr M.', 'Khashoggi, Khalid', 'Nicolaou, Savvas', 'Müller, Nestor L.']",,,,
,PMC,Accessing the human repertoire for broadly neutralizing HIV antibodies,,PMC2840234,,,"The human antibody response has special significance in the ongoing efforts to develop a protective HIV vaccine. The observation that a subset of HIV infected individuals, who do not develop AIDS, have a broadly neutralizing antibody response has drawn attention to deciphering the nature of this response. It is hoped that an understanding of these protective antibodies, developed over time in response to the ongoing accumulation of mutations in the infecting virus, will facilitate the development of a vaccine that can elicit a similar response. This strategy will be greatly aided by the identification of broadly neutralizing monoclonal HIV antibodies from infected individuals. Several methods have been utilized to isolate and characterize individual antibodies from the human repertoire and each of these methods has been applied to the generation of broadly neutralizing HIV antibodies, albeit with differing rates of success. This review describes several of these methods including human hybridoma; EBV transformation; nonimmortalized B cell culture; clonal sorting; and combinatorial display. Key considerations used in the comparison of different methods includes: efficiency of interrogation of an individual’s entire repertoire; assay formats that can be used to screen for antibodies of interest (i.e., binding versus biological assays); and the ability to recover native antibody heavy and light chain pairs.",,"Hammond, Philip W",,,,
,PMC,"Carbohydrate Recognition by Boronolectins, Small Molecules, and Lectins",http://dx.doi.org/10.1002/med.20155,PMC2829346,,,"Carbohydrates are known to mediate a large number of biological and pathological events. Small and macromolecules capable of carbohydrate recognition have great potentials as research tools, diagnostics, vectors for targeted delivery of therapeutic and imaging agents, and therapeutic agents. However, this potential is far from being realized. One key issue is the difficulty in the development of “binders” capable of specific recognition of carbohydrates of biological relevance. This review discusses systematically the general approaches that are available in developing carbohydrate sensors and “binders/receptors,” and their applications. The focus is on discoveries during the last five years.",,"['Jin, Shan', 'Cheng, Yunfeng', 'Reid, Suazette', 'Li, Minyong', 'Wang, Binghe']",,,,
,PMC,A zinc-binding site by negative selection induces metallodrug susceptibility in an essential chaperonin,http://dx.doi.org/10.1073/pnas.0913970107,PMC2841863,,,"GroES is an indispensable chaperonin virtually found throughout all life forms. Consequently, mutations of this protein must be critically scrutinized by natural selection. Nevertheless, the homolog from a potentially virulent gastric pathogen, Helicobacter pylori, strikingly features a histidine/cysteine-rich C terminus that shares no significant homology with other family members. Additionally, three more (H45, C51, and C53) are uniquely present in its apical domain. The statistical analyses show that these residues may have originated from negative selection, presumably driven by either dependent or independent amino acid mutations. In the absence of the C-terminal metal-binding domain, the mutant protein still exhibits a substantial capacity for zinc binding in vivo. The biochemical properties of site-directed mutants indicate that H45, C51, and C53 make up an oxidation-sensitive zinc-binding site that may donate the bound metal to a zinc acceptor. Of interest, bismuth antiulcer drugs strongly bind at this site (K(d) of approximately 7 × 10(-26) M), replacing the bound zinc and consequently inducing the disruption of the quaternary structure. Because biological features by negative selection are usually inert to change during evolution, this study sheds light on a promising field whereby medicines can be designed or improved to specifically target the residues that uniquely evolved in pathogenic proteins so as to retard the emergence of drug resistance.",,"['Cun, Shujian', 'Sun, Hongzhe']",,,,
,PMC,"Impact of Non-Pharmaceutical Interventions on URIs and Influenza in Crowded, Urban Households",,PMC2821845,,,"OBJECTIVE: We compared the impact of three household interventions—education, education with alcohol-based hand sanitizer, and education with hand sanitizer and face masks—on incidence and secondary transmission of upper respiratory infections (URIs) and influenza, knowledge of transmission of URIs, and vaccination rates. METHODS: A total of 509 primarily Hispanic households participated. Participants reported symptoms twice weekly, and nasal swabs were collected from those with an influenza-like illness (ILI). Households were followed for up to 19 months and home visits were made at least every two months. RESULTS: We recorded 5,034 URIs, of which 669 cases reported ILIs and 78 were laboratory-confirmed cases of influenza. Demographic factors significantly associated with infection rates included age, gender, birth location, education, and employment. The Hand Sanitizer group was significantly more likely to report that no household member had symptoms (p<0.01), but there were no significant differences in rates of infection by intervention group in multivariate analyses. Knowledge improved significantly more in the Hand Sanitizer group (p<0.0001). The proportion of households that reported ≥50% of members receiving influenza vaccine increased during the study (p<0.001). Despite the fact that compliance with mask wearing was poor, mask wearing as well as increased crowding, lower education levels of caretakers, and index cases 0–5 years of age (compared with adults) were associated with significantly lower secondary transmission rates (all p<0.02). CONCLUSIONS: In this population, there was no detectable additional benefit of hand sanitizer or face masks over targeted education on overall rates of URIs, but mask wearing was associated with reduced secondary transmission and should be encouraged during outbreak situations. During the study period, community concern about methicillin-resistant Staphylococcus aureus was occurring, perhaps contributing to the use of hand sanitizer in the Education control group, and diluting the intervention's measurable impact.",,"['Larson, Elaine L.', 'Ferng, Yu-hui', 'Wong-McLoughlin, Jennifer', 'Wang, Shuang', 'Haber, Michael', 'Morse, Stephen S.']",,,,
,PMC,"Capture and sequence analysis of RNAs with terminal 2′,3′-cyclic phosphates",http://dx.doi.org/10.1261/rna.1934910,PMC2822926,,,"The combination of ligation-based RNA capture methods and high-throughput sequencing has facilitated the characterization of transcriptomes and the identification of novel noncoding RNAs. However, current ligation-based RNA capture methods require RNA substrates with terminal 3′-hydroxyl groups, limiting their utility for identifying RNAs with modified termini like 2′,3′-cyclic phosphates. Cyclic phosphate-terminated RNAs are generated by endonucleolytic cleavages and self-cleaving ribozymes and are found as stable modifications on cellular RNAs such as the U6 spliceosomal RNA. We developed a method that uses the Arabidopsis thaliana tRNA ligase to add an adaptor oligonucleotide to RNAs that terminate in 2′,3′-cyclic phosphates. The adaptor allows specific priming by reverse transcriptase, which is followed by additional steps for PCR amplification and high-throughput DNA sequencing. Applying the method to total human RNA, we found 2836 sequencing reads corresponding to the 3′ terminus of U6 snRNA, validating the method. In addition to a large background of reads that map throughout abundantly transcribed RNAs, we also found 42,324 reads of specific fragments from several tRNA isoacceptor families, suggesting that this method may identify processing events previously undetected by other RNA cloning techniques.",,"['Schutz, Kevin', 'Hesselberth, Jay R.', 'Fields, Stanley']",,,,
,PMC,Newsprint media representations of the introduction of the HPV vaccination programme for cervical cancer prevention in the UK (2005–2008),http://dx.doi.org/10.1016/j.socscimed.2009.11.027,PMC2835855,20064682,CC BY,"In September 2008, the human papillomavirus (HPV) immunisation programme was introduced in the UK for schoolgirls aged between 12 and 18 years of age. The vaccine shows high efficacy in preventing infection against HPV types 16 and 18 responsible for 70% of cervical cancer. However, to be most effective, the vaccine needs to be administered before exposure to the viruses and therefore, ideally, before young people become sexually active. The introduction of any new vaccine, and perhaps particularly one given to young teenage girls to prevent a sexually transmitted cancer-causing virus, has the potential to attract a great deal of media attention. This paper reports on content analysis of 344 articles published between January 2005 and December 2008 in 15 UK newspapers. It includes both manifest and latent analysis to examine newsprint media coverage of the introduction of the HPV vaccination programme and its role in HPV advocacy. We concluded that the newspapers were generally positive towards the new HPV vaccination and that over the 4 years period the newsworthiness of the HPV vaccination programme increased. In 2008 two events dominated coverage, firstly, the introduction of the HPV programme in September 2008 and secondly, in August 2008 the diagnosis on camera of cervical cancer given to Jade Goody, a 27 year old mother of two, who gained fame and notoriety in the UK through her participation in several reality television shows. There are two conclusions from this study. Firstly, the positive media coverage surrounding the introduction of the HPV vaccination programme is to be welcomed as it is likely to contribute towards influencing public perceptions about the acceptability and need for HPV vaccination. Secondly, the focus on prevalence rates of HPV infection among women and on women's sexual behaviours, in relation to HPV vaccination ‘encouraging’ promiscuity, is an unhelpful aspect of media coverage.",2010 Mar,"['Hilton, Shona', 'Hunt, Kate', 'Langan, Mairi', 'Bedford, Helen', 'Petticrew, Mark']",Soc Sci Med,,,
,PMC,Ecology of Rabies Virus Exposure in Colonies of Brazilian Free-Tailed Bats (Tadarida brasiliensis) at Natural and Man-Made Roosts in Texas,http://dx.doi.org/10.1089/vbz.2008.0163,PMC2944840,,,"Previous studies have investigated rabies virus (RABV) epizootiology in Brazilian free-tailed bats (Tadarida brasiliensis) in natural cave roosts. However, little is known about geographic variation in RABV exposure, or if the use of man-made roosts by this species affects enzootic RABV infection dynamics within colonies. We sampled rabies viral neutralizing antibodies in bats at three bridge and three cave roosts at multiple time points during the reproductive season to investigate temporal and roost variation in RABV exposure. We report seropositive bats in all age and sex classes with minimal geographic variation in RABV seroprevalence among Brazilian free-tailed bat colonies in south-central Texas. While roost type was not a significant predictor of RABV seroprevalence, it was significantly associated with seasonal fluctuations, suggesting patterns of exposure that differ between roosts. Temporal patterns suggest increased RABV seroprevalence after parturition in cave colonies, potentially related to an influx of susceptible young, in contrast to more uniform seroprevalence in bridge colonies. This study highlights the importance of life history and roost ecology in understanding patterns of RABV seroprevalence in colonies of the Brazilian free-tailed bat.",,"['Turmelle, Amy S.', 'Allen, Louise C.', 'Jackson, Felix R.', 'Kunz, Thomas H.', 'Rupprecht, Charles E.', 'McCracken, Gary F.']",,,,
,PMC,Delayed Kinetics of Poliovirus RNA Synthesis in a Human Cell Line with Reduced Levels of hnRNP C Proteins,http://dx.doi.org/10.1016/j.virol.2010.01.031,PMC2844484,,,"The hnRNP C heterotetramer [(C1(3))C2] binds RNA polymerase II transcripts in the nucleus, along with other proteins of the core hnRNP complex, and plays an important role in mRNA biogenesis and transport. Infection of HeLa cells with poliovirus causes hnRNP C to relocalize from the nucleus, where it is normally retained during interphase, to the cytoplasm. We have proposed that in the cytoplasm, the protein isoforms of hnRNP C participate in the recognition of viral specific RNAs by the poliovirus replication proteins and/or in the assembly of membrane-bound RNA replication complexes. In SK-OV-3 cells, which express reduced levels of hnRNP C compared to HeLa cells or 293 cells, the kinetics of poliovirus replication are delayed. hnRNP C is also re-localized from the nucleus to the cytoplasm in SK-OV-3 cells infected with poliovirus. Increased expression of hnRNP C in SK-OV-3 cells by transient transfection increases the rate of virus production and overall yield over that seen in mock-transfected cells. We propose that hnRNP C interacts with poliovirus RNA and replication proteins to increase the efficiency of viral genomic RNA synthesis.",,"['Brunner, Jo Ellen', 'Ertel, Kenneth J.', 'Rozovics, Janet M.', 'Semler, Bert L.']",,,,
,PMC,Immunization of cattle with recombinant Newcastle disease virus expressing bovine herpesvirus-1 (BHV-1) glycoprotein D induces mucosal and serum antibody responses and provides partial protection against BHV-1,http://dx.doi.org/10.1016/j.vaccine.2010.02.051,PMC3428038,,,"Bovine herpesvirus-1 (BHV-1) is a major cause of respiratory tract diseases in cattle. Vaccination of cattle against BHV-1 is a high priority. A major concern of currently modified live BHV-1 vaccines is their ability to cause latent infection and subsequent reactivation resulting in many outbreaks. Thus, there is a need for alternative strategies. We generated two recombinant Newcastle disease viruses (NDVs) expressing the glycoprotein D (gD) of BHV-1 from an added gene. One recombinant, rLaSota/gDFL, expressed gD without any modification. The other recombinant, rLaSota/gDF, expressed a chimeric gD in which the ectodomain of gD was fused with the transmembrane domain and cytoplasmic tail of the NDV fusion F glycoprotein. Remarkably, the native gD expressed by rLaSota/gDFL virus was incorporated into the NDV virion 2.5-fold more efficiently than the native NDV proteins, whereas the chimeric gD was not detectably incorporated even though it was abundantly expressed on the infected cell surface. The expression of gD did not increase the virulence of the rNDV vectors in chickens. A single intranasal and intratracheal inoculation of calves with either recombinant NDV elicited mucosal and systemic antibodies specific to BHV-1, with the responses to rLaSota/gDFL being higher than those to rLaSota/gDF. Following challenge with BHV-1, calves immunized with the recombinant NDVs had lower titers and earlier clearance of challenge virus compared to the empty vector control, and reduced disease was observed with rLaSota/gDFL. Following challenge, the titers of serum antibodies specific to BHV-1 were higher in the animals immunized with the rNDV vaccines compared to the rNDV parent virus, indicating that the vaccines primed for secondary responses. Our data suggest that NDV can be used as a vaccine vector in bovines and that BHV-1 gD may be useful in mucosal vaccine against BHV-1 infection, but might require augmentation by a second dose or the inclusion of additional BHV-1 antigens.",,"['Khattar, Sunil K.', 'Collins, Peter L.', 'Samal, Siba K.']",,,,
,PMC,Egg-independent vaccine strategies for highly pathogenic H5N1 influenza viruses,,PMC2888842,,,"The emergence of a highly pathogenic H5N1 influenza virus in Hong Kong in 1997 and the subsequent appearance of other H5N1 strains and their spread to several countries in south-east Asia, Africa, the Middle East, and Europe has evoked fear of a global influenza pandemic. Vaccines offer the best hope to combat the threat of an influenza pandemic. However, the global demand for a pandemic vaccine cannot be fulfilled by the current egg-based vaccine manufacturing strategies, thus creating a need to explore alternative technologies for vaccine production and delivery. Several egg-independent vaccine approaches such as cell culture-derived whole virus or subvirion vaccines, recombinant protein-based vaccines, virus-like particle (VLP) vaccines, DNA vaccines and viral vector-based vaccines are currently being investigated and appear promising both in preclinical and clinical studies. The present review will highlight the various egg-independent alternative vaccine approaches for pandemic influenza.",,"['Pandey, Aseem', 'Singh, Neetu', 'Sambhara, Suryaprakash', 'Mittal, Suresh K.']",,,,
,PMC,Deubiquitinating and Interferon Antagonism Activities of Coronavirus Papain-Like Proteases,http://dx.doi.org/10.1128/JVI.02406-09,PMC2863753,,,"Coronaviruses encode multifunctional proteins that are critical for viral replication and for blocking the innate immune response to viral infection. One such multifunctional domain is the coronavirus papain-like protease (PLP), which processes the viral replicase polyprotein, has deubiquitinating (DUB) activity, and antagonizes the induction of type I interferon (IFN). Here we characterized the DUB and IFN antagonism activities of the PLP domains of human coronavirus NL63 and severe acute respiratory syndrome (SARS) coronavirus to determine if DUB activity mediates interferon antagonism. We found that NL63 PLP2 deconjugated ubiquitin (Ub) and the Ub-line molecule ISG15 from cellular substrates and processed both lysine-48- and lysine-63- linked polyubiquitin chains. This PLP2 DUB activity was dependent on an intact catalytic cysteine residue. We demonstrated that in contrast to PLP2 DUB activity, PLP2-mediated interferon antagonism did not require enzymatic activity. Furthermore, addition of an inhibitor that blocks coronavirus protease/DUB activity did not abrogate interferon antagonism. These results indicated that a component of coronavirus PLP-mediated interferon antagonism was independent of protease and DUB activity. Overall, these results demonstrate the multifunctional nature of the coronavirus PLP domain as a viral protease, DUB, and IFN antagonist and suggest that these independent activities may provide multiple targets for antiviral therapies.",,"['Clementz, Mark A.', 'Chen, Zhongbin', 'Banach, Bridget S.', 'Wang, Yanhua', 'Sun, Li', 'Ratia, Kiira', 'Baez-Santos, Yahira M.', 'Wang, Jie', 'Takayama, Jun', 'Ghosh, Arun K.', 'Li, Kui', 'Mesecar, Andrew D.', 'Baker, Susan C.']",,,,
,PMC,Potent Vesicular Stomatitis Virus-Based Avian Influenza Vaccines Provide Long-Term Sterilizing Immunity against Heterologous Challenge,http://dx.doi.org/10.1128/JVI.02637-09,PMC2863739,,,"The emergence in 1997 and continuance today of a highly lethal H5N1 avian influenza virus (AIV) causing human disease has raised concern about an impending pandemic and the need for a vaccine to prepare for such an occurrence. We previously generated an efficacious vesicular stomatitis virus (VSV)-based AIV vaccine expressing H5 hemagglutinin (HA) from the fifth genomic position of VSV (J. A. Schwartz et al., Virology 366:166-173, 2007). Here we have generated and characterized VSV-based vaccines that express the A/Hong Kong/156/1997 (clade 0) H5 HA from the first position of the VSV genome. These vectors induce broadly cross-neutralizing antibodies against homologous and heterologous H5N1 viruses of different clades in mice. The vaccines provide complete protection against morbidity and mortality after heterologous challenge with clade 0 and clade 1 strains in animals even 1 year after vaccination. Postchallenge pulmonary virus loads show that these vectors provide sterilizing immunity. Therefore, VSV-based AIV vaccines are potent, broadly cross-protective pandemic vaccine candidates.",,"['Schwartz, Jennifer A.', 'Buonocore, Linda', 'Suguitan, Amorsolo L.', 'Silaghi, Alex', 'Kobasa, Darwyn', 'Kobinger, Gary', 'Feldmann, Heinz', 'Subbarao, Kanta', 'Rose, John K.']",,,,
,PMC,The Length of and Nonhydrophobic Residues in the Transmembrane Domain of Dengue Virus Envelope Protein Are Critical for Its Retention and Assembly in the Endoplasmic Reticulum,http://dx.doi.org/10.1128/JVI.01963-09,PMC2863728,,,"The morphogenesis of many enveloped viruses, in which viral nucleocapsid complex interacts with envelope (E) protein, is known to take place at various sites along the secretory pathway. How viral E protein retains in a particular intracellular organelle for assembly remains incompletely understood. In this study, we investigated determinants in the E protein of dengue virus (DENV) for its retention and assembly in the endoplasmic reticulum (ER). A chimeric experiment between CD4 and DENV precursor membrane/E constructs suggested that the transmembrane domain (TMD) of E protein contains an ER retention signal. Substitutions of three nonhydrophobic residues at the N terminus of the first helix (T1) and at either the N or C terminus of the second helix of the TMD with three hydrophobic residues, as well as an increase in the length of T1, led to the release of chimeric CD4 and E protein from the ER, suggesting that short length and certain nonhydrophobic residues of the TMD are critical for ER retention. The analysis of enveloped viruses assembled at the plasma membrane and of those assembled in the Golgi complex and ER revealed a trend of decreasing length and increasing nonhydrophobic residues of the TMD of E proteins. Taken together, these findings support a TMD-dependent sorting for viral E proteins along the secretory pathway. Moreover, similar mutations introduced into the TMD of DENV E protein resulted in the increased production of virus-like particles (VLPs), suggesting that modifications of TMD facilitate VLP production and have implications for utilizing flaviviral VLPs as serodiagnostic antigens and vaccine candidates.",,"['Hsieh, Szu-Chia', 'Tsai, Wen-Yang', 'Wang, Wei-Kung']",,,,
,PMC,Why collect individual-level vaccination data?,http://dx.doi.org/10.1503/cmaj.091515,PMC2826469,,,,,,,,,
,PMC,Antigen Engineering Can Play A Critical Role in the Protective Immunity Elicited by Yersinia pestis DNA Vaccines,http://dx.doi.org/10.1016/j.vaccine.2009.10.059,PMC2830910,,,"The use of a DNA immunization approach to deliver protective antigens against Yersinia pestis (Y. pestis) has been successful in previously reported studies. In the current study, the gene designs for V and F1, two well-studied virulent factors serving as main targets for vaccine development, were altered to explore additional options in hopes of improving the protective immunity of DNA vaccines expressing these two antigens. Compared to the wild type V gene DNA vaccines, the use of codon optimized V gene sequences was effective in improving the antigen expression, titers of anti-V antibody responses, and survival against a mucosal lethal challenge. For the F1 DNA vaccine, removal of the N-terminal hydrophobic region was able to improve protective immunity. However, adding a mammalian signal peptide sequence to F1 actually led to reduced protection despite it inducing slightly higher anti-F1 antibody responses. The F1 gene can be fused with a gene coding for YscF, a newly confirmed partial protective antigen for Y. pestis, to produce DNA vaccines that express fused F1 and YscF antigens. One design, in particular, that had YscF fused to the downstream sequence of F1, produced better protection than separate F1 or YscF DNA vaccines, suggesting a potential synergistic effect between these two antigens. Findings from the above studies indicated that there are multiple approaches to optimize the protective immunity for plague DNA vaccines. Most importantly, proper antigen engineering to produce optimal antigen gene inserts in DNA vaccines can clearly play a major role in the future designs of a wide range of DNA vaccines.",,"['Wang, Shixia', 'Mboudjeka, Innocent', 'Goguen, Jon D.', 'Lu, Shan']",,,,
,PMC,Growth restriction of an experimental live attenuated human parainfluenza virus type 2 vaccine in human ciliated airway epithelium in vitro parallels attenuation in African green monkeys,http://dx.doi.org/10.1016/j.vaccine.2010.01.050,PMC2844349,,,"Human parainfluenza viruses (HPIVs) are common causes of severe pediatric respiratory viral disease. We characterized wild-type HPIV2 infection in an in vitro model of human airway epithelium (HAE) and found that the virus replicates to high titer, sheds apically, targets ciliated cells, and induces minimal cytopathology. Replication of an experimental, live attenuated HPIV2 vaccine strain, containing both temperature sensitive (ts) and non-ts attenuating mutations, was restricted >30-fold compared to rHPIV2-WT in HAE at 32°C and exhibited little productive replication at 37°C. This restriction paralleled attenuation in the upper and lower respiratory tract of African green monkeys, supporting the HAE model as an appropriate and convenient system for characterizing HPIV2 vaccine candidates.",,"['Schaap-Nutt, Anne', 'Scull, Margaret A.', 'Schmidt, Alexander C.', 'Murphy, Brian R.', 'Pickles, Raymond J.']",,,,
,PMC,Distinct effects of knocking down MEK1 and MEK2 on replication of herpes simplex virus type 2,http://dx.doi.org/10.1016/j.virusres.2010.02.007,PMC2860046,,,"During infection, viruses hijack various host cell components and programs for their amplification, among which is the canonical ERK signaling pathway, mainly consisting of three tiered serine/threonine kinases, Raf, MEK and ERK. MEK1 and MEK2 are two isoforms of the kinase operating immediately upstream of ERK, and connecting Raf and ERK by phosphorylating ERK. Previous studies have suggested that different isoforms of MEK have distinct biological functions, although their in vitro kinase function may be redundant. However, little is known about the isoform-specific effects of these kinases on viral propagation. In this study, we showed that herpes simplex virus type 2 (HSV-2) infection of human embryonic kidney (HEK) 293 cells induced a sustained activation of ERK1/2. Inhibition of this ERK activation by U0126, a specific inhibitor of MEK1/2, severely impaired virus production. A similar reduction of virus production was also seen following transfection of cells with siRNAs for MEK1/2. Interestingly, a specific knockdown of MEK1 with siRNAs caused a marked inhibition of viral titers, viral proteins and virus-induced cytopathic effect (CPE), whereas silencing MEK2 had little effect. Therefore, our results demonstrate that MEK1 and MEK2 act differently and that HSV-2 hijacks host MEK1 for its own amplification. To our knowledge, this is the first report showing inhibition of HSV-2 replication by targeting human MEK1. This study also suggests that MEK1 could be a potential target for anti-HSV-2 therapy, which may minimize damage to the host cells engendered by targeting both MEK1 and MEK2.",,"['Zhang, Hao', 'Feng, Hai', 'Luo, Lingqi', 'Zhou, Qi', 'Luo, Zhijun', 'Peng, Yihong']",,,,
,PMC,A polycystin-2 (TRPP2) dimerization domain essential for the function of heteromeric polycystin complexes,http://dx.doi.org/10.1038/emboj.2010.18,PMC2857461,,,"Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in two genes, PKD1 and PKD2, which encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Earlier work has shown that PC1 and PC2 assemble into a polycystin complex implicated in kidney morphogenesis. PC2 also assembles into homomers of uncertain functional significance. However, little is known about the molecular mechanisms that direct polycystin complex assembly and specify its functions. We have identified a coiled coil in the C-terminus of PC2 that functions as a homodimerization domain essential for PC1 binding but not for its self-oligomerization. Dimerization-defective PC2 mutants were unable to reconstitute PC1/PC2 complexes either at the plasma membrane (PM) or at PM-endoplasmic reticulum (ER) junctions but could still function as ER Ca(2+)-release channels. Expression of dimerization-defective PC2 mutants in zebrafish resulted in a cystic phenotype but had lesser effects on organ laterality. We conclude that C-terminal dimerization of PC2 specifies the formation of polycystin complexes but not formation of ER-localized PC2 channels. Mutations that affect PC2 C-terminal homo- and heteromerization are the likely molecular basis of cyst formation in ADPKD.",,"['Giamarchi, Aurélie', 'Feng, Shuang', 'Rodat-Despoix, Lise', 'Xu, Yaoxian', 'Bubenshchikova, Ekaterina', 'Newby, Linda J', 'Hao, Jizhe', 'Gaudioso, Christelle', 'Crest, Marcel', 'Lupas, Andrei N', 'Honoré, Eric', 'Williamson, Michael P', 'Obara, Tomoko', 'Ong, Albert CM', 'Delmas, Patrick']",,,,
,PMC,Angiotensin-converting enzymes and drug discovery in cardiovascular diseases,http://dx.doi.org/10.1016/j.drudis.2010.02.003,PMC3005694,,,"Angiotensin-converting enzyme (ACE) is a major target in the treatment of cardiovascular diseases (CVDs). In addition to ACE, ACE2 – which is a homolog of ACE and promotes the degradation of angiotensin II (AngII) to Ang (1–7) – has been recognized recently as a potential therapeutic target in the management of CVDs. This article reviews different metabolic pathways of ACE and ACE2 (AngI-AngII-AT1 receptors and AngI-Ang (1–7)-Mas receptors) in the regulation of cardiovascular function and their potential in new drug development in the therapy of CVDs. In addition, recent progress in the study of angiotensin and ACE in fetal origins of cardiovascular disease, which might present an interesting field in perinatal medicine and preventive medicine, is briefly summarized.",,"['Shi, Lijun', 'Mao, Caiping', 'Xu, Zhice', 'Zhang, Lubo']",,,,
,PMC,Immunoglobulin heavy chain diversity in Pteropid bats: evidence for a diverse and highly specific antigen binding repertoire,http://dx.doi.org/10.1007/s00251-010-0425-4,PMC2887692,,,"Bats are the natural host reservoir for range of emerging and re-emerging viruses, many of which cause significant morbidity and mortality in other mammals, yet appear to result in no clinical consequences for bats. The ability of bats to coexist with a variety of viruses presents an interesting immunological problem that has not been examined in any detail but which could provide significant insights into the evolution of antiviral mechanisms in mammals. Towards a better understanding of the bat immune system, we analysed the expressed heavy chain variable (VH) regions of antibodies from the black flying fox, Pteropus alecto. The germline repertoire of the closely related Pteropid bat, Pteropus vampyrus, whose genome has been sequenced was also examined for comparative purposes. Representative VH genes were found in all three mammalian VH clans (I, II and III) in both the expressed P. alecto VH repertoire and the germline P. vampyrus VH repertoire. Evidence for the use of multiple heavy chain diversity (DH) and joining (JH) segments for the generation of diverse VDJ rearrangements was also present in the expressed antibody repertoire of P. alecto. The long period of co-evolutionary history of bats with viruses may have resulted in a variety of highly specific VH segments being hardwired into the genomes of bats and may have implications for their ability to successfully cope with a diversity of viral antigens.",,"['Baker, Michelle L.', 'Tachedjian, Mary', 'Wang, Lin-Fa']",,,,
,PMC,Hepatitis B Virus Protein X-induced Expression of the CXC Chemokine IP-10 Is Mediated through Activation of NF-κB and Increases Migration of Leukocytes,http://dx.doi.org/10.1074/jbc.M109.067629,PMC2852955,,,"Interferon-γ inducible protein 10 (IP-10) involves inflammatory cell recruitment and cellular immune damage during virus infection. Although an increase of the peripheral IP-10 level is known in HBV-infected patients, the molecular basis of HBV infection inducing IP-10 expression has remained elusive. In the present study, we demonstrate that hepatitis B virus protein X (HBx) increases IP-10 expression in a dose-dependent manner. Transfection of the HBx-expressing vector into HepG2 cells results in nuclear translocation of NF-κB, which directly binds the promoter of IP-10 at positions from −122 to −113, thus facilitating transcription. The addition of the NF-κB inhibitor blocks the effect of HBx on IP-10 induction. In parallel, increase of NF-κB subunits p65 and p50 in HepG2 cells also augments IP-10 expression. Furthermore, we show that HBx induces activation of NF-κB through the TRAF2/TAK1 signaling pathway, leading to up-regulation of IP-10 expression. As a consequence, up-regulation of IP-10 may mediate the migration of peripheral blood leukocytes in a NF-κB-dependent manner. In conclusion, we report a novel molecular mechanism of HBV infection inducing IP-10 expression, which involves viral protein HBx affecting NF-κB pathway, leading to transactivation of the IP-10 promoter. Our study provides insight into the migration of leukocytes in response to HBV infection, thus causing immune pathological injury of liver.",,"['Zhou, Yu', 'Wang, Shuo', 'Ma, Jing-Wei', 'Lei, Zhang', 'Zhu, Hui-Fen', 'Lei, Ping', 'Yang, Zhuo-Shun', 'Zhang, Biao', 'Yao, Xin-Xin', 'Shi, Chuan', 'Sun, Li-Fang', 'Wu, Xiong-Wen', 'Ning, Qin', 'Shen, Guan-Xin', 'Huang, Bo']",,,,
,PMC,CD8 T-cell cross-reactivity networks mediate heterologous immunity in human Epstein-Barr (EBV) and murine vaccinia (VV) virus infections,http://dx.doi.org/10.4049/jimmunol.0902168,PMC3253758,,,"Here we demonstrate complex networks of CD8 T-cell cross-reactivities between influenza A virus (IAV) and Epstein- Barr virus (EBV) in humans and between lymphocytic choriomeningitis virus (LCMV) and vaccinia virus (VV) in mice. We also show directly that cross-reactive T-cells mediate protective heterologous immunity in mice. Subsets of T-cell populations reactive with one epitope cross-reacted with either of several other epitopes encoded by the same or the heterologous virus. Human T-cells specific to EBV-encoded BMLF1(280-288) could be cross-reactive with two IAV or two other EBV epitopes. Mouse T-cells specific to the VV-encoded a11r(198-205) could be cross-reactive with three different LCMV, one Pichinde virus, or one other VV epitope. Patterns of cross-reactivity differed among individuals, reflecting the private specificities of the host’s immune repertoire, and divergence in the abilities of T-cell populations to mediate protective immunity. Defining such cross-reactive networks between commonly encountered human pathogens may facilitate the design of vaccines.",,"['Cornberg, Markus', 'Clute, Shalyn C.', 'Watkin, Levi B.', 'Saccoccio, Frances M.', 'Kim, Sung-Kwon', 'Naumov, Yuri N.', 'Brehm, Michael A.', 'Aslan, Nuray', 'Welsh, Raymond M.', 'Selin, Liisa K.']",,,,
,PMC,Achieving a Golden Mean: Mechanisms by Which Coronaviruses Ensure Synthesis of the Correct Stoichiometric Ratios of Viral Proteins,http://dx.doi.org/10.1128/JVI.02480-09,PMC2863758,,,"In retroviruses and the double-stranded RNA totiviruses, the efficiency of programmed −1 ribosomal frameshifting is critical for ensuring the proper ratios of upstream-encoded capsid proteins to downstream-encoded replicase enzymes. The genomic organizations of many other frameshifting viruses, including the coronaviruses, are very different, in that their upstream open reading frames encode nonstructural proteins, the frameshift-dependent downstream open reading frames encode enzymes involved in transcription and replication, and their structural proteins are encoded by subgenomic mRNAs. The biological significance of frameshifting efficiency and how the relative ratios of proteins encoded by the upstream and downstream open reading frames affect virus propagation has not been explored before. Here, three different strategies were employed to test the hypothesis that the −1 PRF signals of coronaviruses have evolved to produce the correct ratios of upstream- to downstream-encoded proteins. Specifically, infectious clones of the severe acute respiratory syndrome (SARS)-associated coronavirus harboring mutations that lower frameshift efficiency decreased infectivity by >4 orders of magnitude. Second, a series of frameshift-promoting mRNA pseudoknot mutants was employed to demonstrate that the frameshift signals of the SARS-associated coronavirus and mouse hepatitis virus have evolved to promote optimal frameshift efficiencies. Finally, we show that a previously described frameshift attenuator element does not actually affect frameshifting per se but rather serves to limit the fraction of ribosomes available for frameshifting. The findings of these analyses all support a “golden mean” model in which viruses use both programmed ribosomal frameshifting and translational attenuation to control the relative ratios of their encoded proteins.",,"['Plant, Ewan P.', 'Rakauskaitė, Rasa', 'Taylor, Deborah R.', 'Dinman, Jonathan D.']",,,,
,PMC,The Proteome of Shigella flexneri 2a 2457T Grown at 30 and 37 °C,http://dx.doi.org/10.1074/mcp.M900446-MCP200,PMC2877981,,,"To upgrade the proteome reference map of Shigella flexneri 2a 2457T, the protein expression profiles of log phase and stationary phase cells grown at 30 and 37 °C were thoroughly analyzed using multiple overlapping narrow pH range (between pH 4.0 and 11.0) two-dimensional gel electrophoresis. A total of 723 spots representing 574 protein entries were identified by MALDI-TOF/TOF MS, including the majority of known key virulence factors. 64 hypothetical proteins and six misannotated proteins were also experimentally identified. A comparison between the four proteome maps showed that most of the virulence-related proteins were up-regulated at 37 °C, and the differences were more notable in stationary phase cells, suggesting that the expressions of these virulence factors were not only controlled by temperature but also controlled by the nutrients available in the environment. The expression patterns of some virulence-related genes under the four different conditions suggested that they might also be regulated at the post-transcriptional level. A further significant finding was that the expression of the protein ArgT was dramatically up-regulated at 30 °C. The results of semiquantitative RT-PCR analysis showed that expression of argT was not regulated at the transcriptional level. Therefore, we carried out a series of experiments to uncover the mechanism regulating ArgT levels and found that the differential expression of ArgT was due to its degradation by a periplasmic protease, HtrA, whose activity, but not its synthesis, was affected by temperature. The cleavage site in ArgT was between position 160 (Val) and position 161 (Ala). These results may provide useful insights for understanding the physiology and pathogenesis of S. flexneri.",,"['Zhu, Li', 'Zhao, Ge', 'Stein, Robert', 'Zheng, Xuexue', 'Hu, Wei', 'Shang, Na', 'Bu, Xin', 'Liu, Xiankai', 'Wang, Jie', 'Feng, Erling', 'Wang, Bin', 'Zhang, Xuemin', 'Ye, Qinong', 'Huang, Peitang', 'Zeng, Ming', 'Wang, Hengliang']",,,,
,PMC,"Initial Response of Healthcare Institutions to Emergence of H1N1 Influenza: Experiences, Obstacles, and Perceived Future Needs",http://dx.doi.org/10.1086/650169,PMC2811228,,,"STUDY SUMMARY: Of 323 healthcare epidemiology professionals surveyed during the H1N1 crisis, 30.7% reported shortages of antiviral medication and 39.0% reported stockpiling of antiviral medications. Vaccine development, healthcare worker education, revisions of pandemic plans, and mandatory influenza vaccination were identified as important future initiatives. BACKGROUND: The emergence of H1N1 influenza is cause for great concern. Although one of the most important components of the response to the H1N1 crisis is the work of healthcare epidemiology professionals, the beliefs and experiences of this community are unknown and the optimal approach to managing H1N1 in the future has not been delineated. METHODS: To assess attitudes and responses of healthcare epidemiology professionals to the H1N1 influenza crisis, we conducted a cross-sectional survey of members of the Society for Healthcare Epidemiology of America. We assessed beliefs regarding: 1) importance of H1N1; 2) institutional preparedness; 3) time spent on the H1N1 crisis; and 4) the institution’s response to H1N1. RESULTS: Of 323 respondents, 195 (60.4%) reported their hospitals were well prepared for a pandemic. Furthermore, the majority reported that senior administrators provided adequate political support and resources (85.1% and 80.2%, respectively) to respond to H1N1. However, 163 (50.9%) respondents reported other important infection prevention activities were neglected during the H1N1 crisis. Shortages of antiviral medication were reported by 99 (30.7%) respondents. Furthermore, 126 (39.0%) reported that personal stockpiling of antiviral medications occurred at their institution and 166 (51.4%) reported institutional actions were initiated to prevent personal stockpiling. Also, 294 (91.0%) respondents believed H1N1 influenza would reappear later this year. Vaccine development, healthcare worker education, and revisions of pandemic influenza plans were identified as the most important future initiatives. Finally, 251 (77.7%) respondents felt healthcare workers should be mandated to receive influenza vaccine. CONCLUSIONS: While generally well-prepared for the H1N1 crisis, substantial revisions of pandemic preparedness plans appear necessary. Future efforts to optimize the response to H1N1 should include curtailing personal stockpiling of antivirals and vaccine development with consideration of mandatory vaccination of healthcare workers.",,"['Lautenbach, Ebbing', 'Saint, Sanjay', 'Henderson, David K.', 'Harris, Anthony D.']",,,,
,PMC,CXCR2(+) neutrophils play an essential role in cuprizone-induced demyelination: relevance to multiple sclerosis,http://dx.doi.org/10.1038/nn.2491,PMC2827651,,,"Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system (CNS). Recent studies suggest diverse mechanisms underlying demyelination, including a subset of lesions involving interplay between metabolic insult to oligodendrocytes and inflammatory mediators. For mice of susceptible strains, cuprizone feeding results in oligodendrocyte cell loss and demyelination of the corpus callosum. Remyelination ensues, and has been extensively studied. Cuprizone-induced demyelination remains incompletely characterized. Here we show that mice lacking type 2 CXC chemokine receptor (CXCR2) are relatively resistant to cuprizone-induced demyelination, and CXCR2(+) neutrophils from the circulation play an essential role in cuprizone-induced demyelination. Findings support a novel two-hit process of cuprizone-induced demyelination, mirroring proposals about pathogenesis of MS lesions featuring extensive oligodendrocyte cell loss. These data indicate that cuprizone-induced demyelination will provide a useful model for certain aspects of MS pathogenesis.",,"['Liu, LiPing', 'Belkadi, Abdelmadjid', 'Darnall, Lindsey', 'Hu, Taofang', 'Drescher, Caitlin', 'Cotleur, Anne C.', 'Padovani-Claudio, Dolly', 'He, Tao', 'Choi, Karen', 'Lane, Thomas E.', 'Miller, Robert H.', 'Ransohoff, Richard M.']",,,,
,PMC,Licorice infusion: Chemical profile and effects on the activation and the cell cycle progression of human lymphocytes,http://dx.doi.org/10.4103/0973-1296.59963,PMC2881654,20548933,CC BY,"A licorice infusion (LI) and its major constituents were investigated for their capacity to stimulate the activation and the cell cycle progression of human lymphocytes, measured by the CD69 expression and DNA content, respectively. The chemical profile of LI was determined by high-performance liquid chromatography-diode array detection (HPLC-DAD). Results: Two major components of LI were identified as liquiritin (1) and glycyrrhizin (2); total flavones and flavonols were shown as its minor constituents. The LI (100-800 μg/ml) stimulated the expression of CD69 on lymphocytes in a concentration-independent manner. Values of the activation index (AI) of total lymphocytes treated with LI (100-800 μg/ml) did not differ significantly among them (P < 0.05), but were 50% lower than the AI value exhibited by cells treated with phytohemagglutinin (PHA). The LI showed a similar effect on T cells, but on a lower scale. Compounds 1 and 2 (12-100 μg/ml) did not stimulate the CD69 expression on lymphocytes. The LI, 1 and 2 showed no meaningful effect on cell cycle progression of lymphocytes. The experimental data indicates that LI stimulates the activation of lymphocytes as a result of a proliferation-independent process. This finding suggests that LI could be considered as a potential specific immune stimulator.",2010 Feb 13 Jan-Mar,"['Cheel, José', 'Onofre, Gabriela', 'Vokurkova, Doris', 'Tůmová, Lenka', 'Neugebauerová, Jarmila']",Pharmacogn Mag,,,
,PMC,Self-assembly of Severe Acute Respiratory Syndrome Coronavirus Membrane Protein,http://dx.doi.org/10.1074/jbc.M109.030270,PMC2857088,,,"Coronavirus membrane (M) protein can form virus-like particles (VLPs) when coexpressed with nucleocapsid (N) or envelope (E) proteins, suggesting a pivotal role for M in virion assembly. Here we demonstrate the self-assembly and release of severe acute respiratory syndrome coronavirus (SARS-CoV) M protein in medium in the form of membrane-enveloped vesicles with densities lower than those of VLPs formed by M plus N. Although efficient N-N interactions require the presence of RNA, we found that M-M interactions were RNA-independent. SARS-CoV M was observed in both the Golgi area and plasma membranes of a variety of cells. Blocking M glycosylation does not appear to significantly affect M plasma membrane labeling intensity, M-containing vesicle release, or VLP formation. Results from a genetic analysis indicate involvement of the third transmembrane domain of M in plasma membrane-targeting signal. Fusion proteins containing M amino-terminal 50 residues encompassing the first transmembrane domain were found to be sufficient for membrane binding, multimerization, and Golgi retention. Surprisingly, we found that fusion proteins lacking all three transmembrane domains were still capable of membrane binding, Golgi retention, and interacting with M. The data suggest that multiple SARS-CoV M regions are involved in M self-assembly and subcellular localization.",,"['Tseng, Ying-Tzu', 'Wang, Shiu-Mei', 'Huang, Kuo-Jung', 'Lee, Amber I-Ru', 'Chiang, Chien-Cheng', 'Wang, Chin-Tien']",,,,
,PMC,"The reproduction number of seasonal influenza epidemics in Brazil, 1996–2006",http://dx.doi.org/10.1098/rspb.2009.1897,PMC2871867,,,"The transmission dynamics of influenza in tropical regions are poorly understood. Here we explore geographical variations in the reproduction number of influenza across equatorial, tropical and subtropical areas of Brazil, based on the analysis of weekly pneumonia and influenza (P&I) mortality time series in 27 states. The reproduction number (R) was low on average in Brazil (mean = 1.03 (95% CI 1.02–1.04), assuming a serial interval of 3 days). Estimates of the reproduction number were slightly lower for Brazil than for the USA or France (difference in mean R = 0.08, p < 0.01) and displayed less between-year variation (p < 0.001). Our findings suggest a weak gradient in the reproduction number with population size, where R increases from low population in the North to high population in the South of Brazil. Our low estimates of the reproduction number suggest that influenza population immunity could be high on average in Brazil, potentially resulting in increased viral genetic diversity and rate of emergence of new variants. Additional epidemiological and genetic studies are warranted to further characterize the dynamics of influenza in the tropics and refine our understanding of the global circulation of influenza viruses.",,"['Chowell, Gerardo', 'Viboud, Cécile', 'Simonsen, Lone', 'Miller, Mark', 'Alonso, Wladimir J.']",,,,
,PMC,CD147/EMMPRIN Acts as a Functional Entry Receptor for Measles Virus on Epithelial Cells,http://dx.doi.org/10.1128/JVI.02168-09,PMC2863760,,,"Measles is a highly contagious human disease caused by measles virus (MeV) and remains the leading cause of death in children, particularly in developing countries. Wild-type MeV preferentially infects lymphocytes by using signaling lymphocytic activation molecule (SLAM), whose expression is restricted to hematopoietic cells, as a receptor. MeV also infects other epithelial and neuronal cells that do not express SLAM and causes pneumonia and diarrhea and, sometimes, serious symptoms such as measles encephalitis and subacute sclerosing panencephalitis. The discrepancy between the tissue tropism of MeV and the distribution of SLAM-positive cells suggests that there are unknown receptors other than SLAM for MeV. Here we identified CD147/EMMPRIN (extracellular matrix metalloproteinase inducer), a transmembrane glycoprotein, which acts as a receptor for MeV on epithelial cells. Furthermore, we found the incorporation of cyclophilin B (CypB), a cellular ligand for CD147, in MeV virions, and showed that inhibition of CypB incorporation significantly attenuated SLAM-independent infection on epithelial cells, while it had no effect on SLAM-dependent infection. To date, MeV infection was considered to be triggered by binding of its hemagglutinin (H) protein and cellular receptors. Our present study, however, indicates that MeV infection also occurs via CD147 and virion-associated CypB, independently of MeV H. Since CD147 is expressed in a variety of cells, including epithelial and neuronal cells, this molecule possibly functions as an entry receptor for MeV in SLAM-negative cells. This is the first report among members of the Mononegavirales that CD147 is used as a virus entry receptor via incorporated CypB in the virions.",,"['Watanabe, Akira', 'Yoneda, Misako', 'Ikeda, Fusako', 'Terao-Muto, Yuri', 'Sato, Hiroki', 'Kai, Chieko']",,,,
,PMC,Low pH-Induced Conformational Change in Herpes Simplex Virus Glycoprotein B,http://dx.doi.org/10.1128/JVI.02573-09,PMC2849479,,,"Herpesviruses can enter host cells using pH-dependent endocytosis pathways in a cell-specific manner. Envelope glycoprotein B (gB) is conserved among all herpesviruses and is a critical component of the complex that mediates membrane fusion and entry. Here we demonstrate that mildly acidic pH triggers specific conformational changes in herpes simplex virus (HSV) gB. The antigenic structure of gB was specifically altered by exposure to low pH both in vitro and during entry into host cells. The oligomeric conformation of gB was altered at a similar pH range. Exposure to acid pH appeared to convert virion gB into a lower-order oligomer. The detected conformational changes were reversible, similar to those in other class III fusion proteins. Exposure of purified, recombinant gB to mildly acidic pH resulted in similar changes in conformation and caused gB to become more hydrophobic, suggesting that low pH directly affects gB. We propose that intracellular low pH induces alterations in gB conformation that, together with additional triggers such as receptor binding, are essential for virion-cell fusion during herpesviral entry by endocytosis.",,"['Dollery, Stephen J.', 'Delboy, Mark G.', 'Nicola, Anthony V.']",,,,
,PMC,Direct observation of distinct A/P hybrid-state tRNAs in translocating ribosomes,http://dx.doi.org/10.1016/j.str.2009.12.007,PMC4340587,,,"Transfer RNAs (tRNAs) link the genetic code in the form of messenger RNA (mRNA) to protein sequence. Translocation of tRNAs through the ribosome from aminoacyl (A) site to peptidyl (P) site, and from P-site to exit (E) site is catalysed in eukaryotes by the translocase elongation factor 2 (EF-2), and in prokaryotes by its homologue EF-G. During tRNA movement one or more “hybrid” states (A/P) is occupied, but molecular details of them and of the translocation process are limited. Here we show by cryo-electron microscopy (cryo-EM) that a population of mammalian ribosomes stalled at an mRNA pseudoknot structure contains structurally-distorted tRNAs in two different A/P hybrid states. In one (A/P’) the tRNA is in contact with the translocase EF-2 which induces it. In the other (A/P”) the translocase is absent. The existence of these alternative A/P intermediate states has relevance to our understanding of the mechanics and kinetics of translocation.",,"['Flanagan, John F.', 'Namy, Olivier', 'Brierley, Ian', 'Gilbert, Robert J. C.']",,,,
,PMC,Estimated epidemiologic parameters and morbidity associated with pandemic H1N1 influenza,http://dx.doi.org/10.1503/cmaj.091807,PMC2817319,,,"BACKGROUND: In the face of an influenza pandemic, accurate estimates of epidemiologic parameters are required to help guide decision-making. We sought to estimate epidemiologic parameters for pandemic H1N1 influenza using data from initial reports of laboratory-confirmed cases. METHODS: We obtained data on laboratory-confirmed cases of pandemic H1N1 influenza reported in the province of Ontario, Canada, with dates of symptom onset between Apr. 13 and June 20, 2009. Incubation periods and duration of symptoms were estimated and fit to parametric distributions. We used competing-risk models to estimate risk of hospital admission and case-fatality rates. We used a Markov Chain Monte Carlo model to simulate disease transmission. RESULTS: The median incubation period was 4 days and the duration of symptoms was 7 days. Recovery was faster among patients less than 18 years old than among older patients (hazard ratio 1.23, 95% confidence interval 1.06–1.44). The risk of hospital admission was 4.5% (95% CI 3.8%–5.2%) and the case-fatality rate was 0.3% (95% CI 0.1%–0.5%). The risk of hospital admission was highest among patients less than 1 year old and those 65 years or older. Adults more than 50 years old comprised 7% of cases but accounted for 7 of 10 initial deaths (odds ratio 28.6, 95% confidence interval 7.3–111.2). From the simulation models, we estimated the following values (and 95% credible intervals): a mean basic reproductive number (R(0), the number of new cases created by a single primary case in a susceptible population) of 1.31 (1.25–1.38), a mean latent period of 2.62 (2.28–3.12) days and a mean duration of infectiousness of 3.38 (2.06–4.69) days. From these values we estimated a serial interval (the average time from onset of infectiousness in a case to the onset of infectiousness in a person infected by that case) of 4–5 days. INTERPRETATION: The low estimates for R(0) indicate that effective mitigation strategies may reduce the final epidemic impact of pandemic H1N1 influenza.",,"['Tuite, Ashleigh R.', 'Greer, Amy L.', 'Whelan, Michael', 'Winter, Anne-Luise', 'Lee, Brenda', 'Yan, Ping', 'Wu, Jianhong', 'Moghadas, Seyed', 'Buckeridge, David', 'Pourbohloul, Babak', 'Fisman, David N.']",,,,
,PMC,The early autophagic pathway is activated by hepatitis B virus and required for viral DNA replication,http://dx.doi.org/10.1073/pnas.0911373107,PMC2840127,,,"Autophagy is a catabolic process by which cells remove long-lived proteins and damaged organelles for recycling. Viral infections may also induce autophagic response. Here we show that hepatitis B virus (HBV), a pathogen that chronically infects ≈350 million people globally, can enhance autophagic response in cell cultures, mouse liver, and during natural infection. This enhancement of the autophagic response is not coupled by an increase of autophagic protein degradation and is dependent on the viral X protein, which binds to and enhances the enzymatic activity of phosphatidylinositol 3-kinase class III, an enzyme critical for the initiation of autophagy. Further analysis indicates that autophagy enhances HBV DNA replication, with minimal involvement of late autophagic vacuoles in this process. Our studies thus demonstrate that a DNA virus can use autophagy to enhance its own replication and indicate the possibility of targeting the autophagic pathway for the treatment of HBV patients.",,"['Sir, Donna', 'Tian, Yongjun', 'Chen, Wen-ling', 'Ann, David K.', 'Yen, Tien-Sze Benedict', 'Ou, Jing-hsiung James']",,,,
,PMC,Liberation of SARS-CoV main protease from the viral polyprotein: N-terminal autocleavage does not depend on the mature dimerization mode,http://dx.doi.org/10.1007/s13238-010-0011-4,PMC4875104,,,"The main protease (M(pro)) plays a vital role in proteolytic processing of the polyproteins in the replicative cycle of SARS coronavirus (SARS-CoV). Dimerization of this enzyme has been shown to be indispensable for transcleavage activity. However, the auto-processing mechanism of M(pro), i.e. its own release from the polyproteins through autocleavage, remains unclear. This study elucidates the relationship between the N-terminal autocleavage activity and the dimerization of “immature” M(pro). Three residues (Arg4, Glu290, and Arg298), which contribute to the active dimer conformation of mature M(pro), are selected for mutational analyses. Surprisingly, all three mutants still perform N-terminal autocleavage, while the dimerization of mature protease and transcleavage activity following auto-processing are completely inhibited by the E290R and R298E mutations and partially so by the R4E mutation. Furthermore, the mature E290R mutant can resume N-terminal autocleavage activity when mixed with the “immature” C145A/E290R double mutant whereas its trans-cleavage activity remains absent. Therefore, the N-terminal auto-processing of M(pro) appears to require only two “immature” monomers approaching one another to form an “intermediate” dimer structure and does not strictly depend on the active dimer conformation existing in mature protease. In conclusion, an auto-release model of M(pro) from the polyproteins is proposed, which will help understand the auto-processing mechanism and the difference between the autocleavage and trans-cleavage proteolytic activities of SARS-CoV M(pro).",,"['Chen, Shuai', 'Jonas, Felix', 'Shen, Can', 'Higenfeld, Rolf']",,,,
,PMC,Bat and virus,http://dx.doi.org/10.1007/s13238-010-0029-7,PMC4875169,,,"Bat, the only flying mammal and count more than 20% of the extant mammals on earth, were recently identified as a natural reservoir of emerging and reemerging infectious pathogens. Astonishing amount (more than 70) and genetic diversity of viruses isolated from the bat have been identified in different populations throughout the world. Many studies focus on bat viruses that caused severe domestic and human diseases. However, many viruses were found in apparently healthy bats, suggesting that bats may have a specific immune system or antiviral activity against virus infections. Therefore, basic researches for bat immunology and virus-host interactions are important for understanding bat-derived infectious diseases.",,"Shi, Zhengli",,,,
,PMC,New nsp8 isoform suggests mechanism for tuning viral RNA synthesis,http://dx.doi.org/10.1007/s13238-010-0028-8,PMC4875168,,,"During severe acute respiratory syndrome coronavirus (SARS-CoV) infection, the activity of the replication/transcription complexes (RTC) quickly peaks at 6 hours post infection (h.p.i) and then diminishes significantly in the late post-infection stages. This “down-up-down” regulation of RNA synthesis distinguishes different viral stages: primary translation, genome replication, and finally viron assembly. Regarding the nsp8 as the primase in RNA synthesis, we confirmed that the proteolysis product of the primase (nsp8) contains the globular domain (nsp8C), and indentified the resectioning site that is notably conserved in all the three groups of coronavirus. We subsequently crystallized the complex of SARS-CoV nsp8C and nsp7, and the 3-D structure of this domain revealed its capability to interfuse into the hexadecamer super-complex. This specific proteolysis may indicate one possible mechanism by which coronaviruses to switch from viral infection to genome replication and viral assembly stages.",,"['Li, Shuang', 'Zhao, Qi', 'Zhang, Yinjie', 'Zhang, Yang', 'Bartlam, Mark', 'Li, Xuemei', 'Rao, Zihe']",,,,
,PMC,Application of the Ibis-T5000 Pan-Orthopoxvirus Assay to Quantitatively Detect Monkeypox Viral Loads in Clinical Specimens from Macaques Experimentally Infected with Aerosolized Monkeypox Virus,http://dx.doi.org/10.4269/ajtmh.2010.09-0361,PMC2813175,,,"Monkeypox virus (MPXV), a member of the family Poxviridae and genus Orthopoxvirus, causes a smallpox-like disease in humans. A previously described pan-Orthopoxvirus assay, based on a broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS), was evaluated for its ability to detect MPXV from spiked human and aerosol-infected cynomolgous macaque (Macaca fascicularis) samples. Detection of MPXV DNA from macaque tissue, blood, and spiked human blood by the PCR/ESI-MS pan-Orthopoxvirus assay was comparable, albeit at slightly higher levels, to the current gold standard method of real-time PCR with the pan-Orthopoxvirus assay and had a limit of detection of 200 plaque-forming units. Furthermore, the platform was able to distinguish MPXV and vaccinia viruses that were spiked into macaque blood samples at various concentrations. This platform provides a new tool for the diagnosis and monitoring of orthopoxviral loads during vaccine or antiviral studies, but also could provide rapid identification during natural outbreaks or bioterrorism attacks.",,"['Grant, Rebecca J.', 'Baldwin, Carson D.', 'Nalca, Aysegul', 'Zoll, Scott', 'Blyn, Lawrence B.', 'Eshoo, Mark W.', 'Matthews, Heather', 'Sampath, Rangarajan', 'Whitehouse, Chris A.']",,,,
,PMC,Five HLA-DP Molecules Frequently Expressed in the Worldwide Human Population Share a Common HLA Supertypic Binding Specificity,http://dx.doi.org/10.4049/jimmunol.0903655,PMC2935290,,,"Compared with DR and DQ, knowledge of the binding repertoires and specificities of HLA-DP alleles is somewhat limited. However, a growing body of literature has indicated the importance of DP-restricted responses in the context of cancer, allergy, and infectious disease. In the current study, we developed high-throughput binding assays for the five most common HLA-DPB1 alleles in the general worldwide population. Using these assays on a comprehensive panel of single-substitution analogs and large peptide libraries, we derived novel detailed binding motifs for DPB1*0101 and DPB1*0501. We also derived more detailed quantitative motifs for DPB1*0201, DPB1*0401, and DPB1*0402, which were previously characterized on the basis of sets of eluted ligands and/or limited sets of substituted peptides. Unexpectedly, all five DP molecules, originally selected only on the basis of their frequency in human populations, were found to share largely overlapping peptide motifs. Testing panels of known DP epitopes and a panel of peptides spanning a set of Phleum pratense Ags revealed that these molecules also share largely overlapping peptide-binding repertoires. This demonstrates that a previously hypothesized DP supertype extends far beyond what was originally envisioned and includes at least three additional very common DP specificities. Taken together, these DP supertype molecules are found in >90% of the human population. Thus, these findings have important implications for epitope-identification studies and monitoring of human class II-restricted immune responses.",,"['Sidney, John', 'Steen, Amiyah', 'Moore, Carrie', 'Ngo, Sandy', 'Chung, Jolan', 'Peters, Bjoern', 'Sette, Alessandro']",,,,
,PMC,The small 11kDa nonstructural protein of human parvovirus B19 plays a key role in inducing apoptosis during B19 virus infection of primary erythroid progenitor cells,http://dx.doi.org/10.1182/blood-2009-04-215756,PMC2817633,,,"Human parvovirus B19 (B19V) infection shows a strong erythroid tropism and drastically destroys erythroid progenitor cells, thus leading to most of the disease outcomes associated with B19V infection. In this study, we systematically examined the 3 B19V nonstructural proteins, 7.5kDa, 11kDa, and NS1, for their function in inducing apoptosis in transfection of primary ex vivo–expanded erythroid progenitor cells, in comparison with apoptosis induced during B19V infection. Our results show that 11kDa is a more significant inducer of apoptosis than NS1, whereas 7.5kDa does not induce apoptosis. Furthermore, we determined that caspase-10, an initiator caspase in death receptor signaling, is the most active caspase in apoptotic erythroid progenitors induced by 11kDa and NS1 as well as during B19V infection. More importantly, cytoplasm-localized 11kDa is expressed at least 100 times more than nucleus-localized NS1 at the protein level in primary erythroid progenitor cells infected with B19V; and inhibition of 11kDa expression using antisense oligos targeting specifically to the 11kDa-encoding mRNAs reduces apoptosis significantly during B19V infection of erythroid progenitor cells. Taken together, these results demonstrate that the 11kDa protein contributes to erythroid progenitor cell death during B19V infection.",,"['Chen, Aaron Yun', 'Zhang, Elizabeth Yan', 'Guan, Wuxiang', 'Cheng, Fang', 'Kleiboeker, Steve', 'Yankee, Thomas M.', 'Qiu, Jianming']",,,,
,PMC,Effects of Stress on the Immune Response to Theiler's Virus – Implications for Virus-Induced Autoimmunity,http://dx.doi.org/10.1159/000258715,PMC2857642,,,"Psychological stress is an important factor in susceptibility to many diseases. Our laboratory has been investigating the impact of stress on the susceptibility to Theiler's virus-induced demyelination (TVID), a mouse model of multiple sclerosis. Using immunodominant viral peptides specific for identification of either CD4(+) or CD8(+) T cells, stress reduced IFN-γ-producing virus-specific CD4(+) and CD8(+) T cells in the spleen and CD8(+) T cells in the CNS. Expression of mRNA for the Th1 transcription factor T-bet and the Th2 transcription factor GATA-3 were decreased in spleen cells isolated from stressed mice. Cytokine production by cells isolated from the CNS or spleens following stimulation with virus indicated that stress decreased both type 1 and type 2 responses. The adverse effects of stress were partially reversed by concurrent RU486 administration but mimicked by dexamethasone, indicating a major role for glucocorticoids. Global stress-induced immunosuppression resulted in higher levels of virus replication and dissemination. The higher viral load subsequently led to an earlier disease onset and more severe clinical and histological signs of demyelinating disease. Our results have important implications for understanding the pathogenesis of MS, and suggest that stressful events during early infection with an agent capable of inducing demyelination may result in immunosuppression and failure to eliminate the pathogen, which in turn may lead to the development of MS.",,"['Welsh, C. Jane', 'Steelman, Andrew J.', 'Mi, Wentao', 'Young, Colin R.', 'Dean, Dana D.', 'Storts, Ralph', 'Welsh, Jr., Thomas H.', 'Meagher, Mary W.']",,,,
,PMC,Identification of N-linked carbohydrates from severe acute respiratory syndrome (SARS) spike glycoprotein,http://dx.doi.org/10.1016/j.virol.2009.12.020,PMC3412594,,,"N-glycans were released from the SARS coronavirus (SARS-CoV) spike glycoprotein produced in Vero E6 cells and their structures were determined by a combination of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, negative ion electrospray collision-induced dissociation time-of-flight mass spectrometry and normal-phase high-performance liquid chromatography with exoglycosidase digestion. Major glycans were high-mannose (Man(5–9)GlcNAc(2)), hybrid and bi-, tri- and tetra-antennary complex with and without bisecting GlcNAc and core fucose. Complex glycans with fewer than the full complement of galactose residues were present and sialylation was negligible. Treatment with the glucosidase inhibitor N-butyl-deoxynojirimycin (NB-DNJ) inhibited N-glycan processing as evidenced by the appearance of glycans of composition Glc(3)Man(7–9)GlcNAc(2). However, some complex glycans remained suggesting the presence of an α-endomannosidase. Our data in tissue culture indicate that inhibition of N-glycan processing may be considered as a therapeutic strategy against SARS CoV infections.",,"['Ritchie, Gayle', 'Harvey, David J.', 'Feldmann, Friederike', 'Stroeher, Ute', 'Feldmann, Heinz', 'Royle, Louise', 'Dwek, Raymond A.', 'Rudd, Pauline M.']",,,,
,PMC,Mucosal parainfluenza virus-vectored vaccine against Ebola virus replicates in the respiratory tract of vector-immune monkeys and is immunogenic,http://dx.doi.org/10.1016/j.virol.2010.01.015,PMC2842940,,,"We previously used human parainfluenza virus type 3 (HPIV3) as a vector to express the Ebola virus (EBOV) GP glycoprotein. The resulting HPIV3/EboGP vaccine was immunogenic and protective against EBOV challenge in a non-human primate model. However it remained unclear whether the vaccine would be effective in adults due to pre-existing immunity to HPIV3. Here, the immunogenicity of HPIV3/EboGP was compared in HPIV3-naïve and HPIV3-immune Rhesus monkeys. After a single dose of HPIV3/EboGP, the titers of EBOV-specific serum ELISA or neutralization antibodies were substantially less in HPIV3-immune animals compared to HPIV3-naïve animals. However, after two doses, which were previously determined to be required for complete protection against EBOV challenge, the antibody titers were indistinguishable between the two groups. The vaccine virus appeared to replicate, at a reduced level, in the respiratory tract despite the pre-existing immunity. This may reflect the known ability of HPIV3 to re-infect, and may also reflect the presence of EBOV GP in the vector virion, which confers resistance to neutralization in vitro by HPIV3-specific antibodies. These data suggest that HPIV3/EboGP will be immunogenic in adults as well as children.",,"['Bukreyev, Alexander A.', 'DiNapoli, Joshua M.', 'Yang, Lijuan', 'Murphy, Brian R.', 'Collins, Peter L.']",,,,
,PMC,The lessons of SARS in Hong Kong,http://dx.doi.org/10.7861/clinmedicine.10-1-50,PMC4954481,,,"Severe acute respiratory syndrome (SARS) is a novel coronavirus infection which broke out in Hong Kong in March 2003. Princess Margaret Hospital was designated to manage this new, mysterious and serious disease. Healthcare workers had to work under extremely stressful and often risky conditions to care for patients. Despite manpower and equipment reinforcements, staff infection occurred as a result of bodily exhaustion, working in an unfamiliar environment and lapses in infection control. Patients suffered even more, not only due to physical discomfort, but also because of the fear of isolation and death away from family and friends. Health authorities learnt their lessons in the outbreak and formulated emergency plans for future infectious disease epidemics. The healthcare infrastructure has been examined and upgraded with regard to intensive care capacity, infection control measures, professional training, manpower deployment, staff facilities, and stockpiling of drugs and personal protective equipment.",,"['Thomas, Sik To Lai', 'Wai, Cho Yu']",,,,
,PMC,Spontaneous Coagulopathy in Inbred WAG/RijYcb Rats,,PMC2826081,,,"Here we describe a series of cases of spontaneous coagulopathy in a colony of inbred WAG/RijYcb (WAG/RijY) rats. This strain previously had been bred at our institution without symptomatology for several decades. The index case was a 10-wk-old male rat that developed a large hematoma at a subcutaneous injection site. Clinicopathologic findings included a decreased RBC count, decreased hematocrit, decreased hemoglobin concentration, normal PT, and prolonged (50% to 70%) aPTT (52 s; reference, 15 to 33 s). Examination of additional WAG/RijY rats that died unexpectedly or had clinical signs of bleeding in the absence of experimental manipulation also revealed normal PT and prolonged aPTT. Histologic examinations of tissues from all rats were unremarkable except for severe acute focally extensive hemorrhage corresponding to the macroscopic findings of acute hemorrhage. Furthermore the aPTT in 8 clinically normal adult rats and 8 clinically normal 4-wk-old WAG/RijY littermates of both sexes was prolonged. We conclude that these WAG/RijY rats have an inherited defect in the intrinsic coagulation pathway.",,"['Booth, Carmen J', 'Brooks, Marjory B', 'Rockwell, Sara']",,,,
,PMC,Role of infection in the development and exacerbation of asthma,http://dx.doi.org/10.1586/ers.09.60,PMC2840256,,,"Respiratory infections are associated with wheezing illnesses in all ages and may also impact the development and severity of asthma. Respiratory tract infections caused by viruses, Chlamydophila or Mycoplasma have been hypothesized to have significant roles in the pathogenesis of asthma. Progress is being made toward establishing the mechanisms by which these agents can cause acute wheezing and impact the pathophysiology of asthma. Host factors probably contribute to the risk of asthma inception and exacerbation, and these contributions may also vary with respect to early- versus adult-onset disease. This review discusses these various associations as they pertain to the development and exacerbation of asthma.",,"['Guilbert, Theresa W', 'Denlinger, Loren C']",,,,
,PMC,Advances in the design and delivery of peptide subunit vaccines with a focus on Toll-like receptor agonists,http://dx.doi.org/10.1586/erv.09.160,PMC2837080,,,"Considerable success has been made with many peptide antigen formulations, and peptide-based vaccines are emerging as the next generation of prophylactic and remedial immunotherapy. However, finding an optimal platform balancing all of the requirements for an effective, specific and safe immune response remains a major challenge for many infectious and chronic diseases. This review outlines how peptide immunogenicity is influenced by the way in which peptides are presented to the immune system, underscoring the need for multifunctional delivery systems that couple antigen and adjuvant into a single construct. Particular attention is given to the ability of Toll-like receptor agonists to act as adjuvants. A survey of recent approaches to developing peptide antigen delivery systems is given, many of which incorporate Toll-like receptor agonists into the design.",,"['Black, Matthew', 'Trent, Amanda', 'Tirrell, Matthew', 'Olive, Colleen']",,,,
,PMC,Global approaches to study protein–protein interactions among viruses and hosts,http://dx.doi.org/10.2217/fmb.10.7,PMC2832059,,,"While high-throughput protein–protein interaction screens were first published approximately 10 years ago, systematic attempts to map interactions among viruses and hosts started only a few years ago. HIV–human interactions dominate host–pathogen interaction databases (with approximately 2000 interactions) despite the fact that probably none of these interactions have been identified in systematic interaction screens. Recently, combinations of protein interaction data with RNAi and other functional genomics data allowed researchers to model more complex interaction networks. The rapid progress in this area promises a flood of new data in the near future, with clinical applications as soon as structural and functional genomics catches up with next-generation sequencing of human variation and structure-based drug design.",,"['Mendez-Rios, Jorge', 'Uetz, Peter']",,,,
,PMC,Infection in systemic lupus erythematosus: friend or foe?,http://dx.doi.org/10.2217/ijr.09.72,PMC2830655,,,"Infectious agents have long been implicated in the pathogenesis of systemic lupus erythematosus. Common viruses, such as the Epstein-Barr virus, transfusion transmitted virus, parvovirus and cytomegalovirus, have an increased prevalence in patients with systemic lupus erythematosus. They may contribute to disease pathogenesis through triggering autoimmunity via structural or functional molecular mimicry, encoding proteins that induce cross-reactive immune responses to self antigens or modulate antigen processing, activation, or apoptosis of B and T cells, macrophages or dendritic cells. Alternatively, some infectious agents, such as malaria, Toxoplasma gondii and Helicobacter pylori, may have a protective effect. Vaccinations may play dual roles by protecting against friend and foe alike.",,"['Francis, Lisa', 'Perl, Andras']",,,,
,PMC,Optimizing HIV Care by Expanding the Nursing Role: Patient and Provider Perspectives,http://dx.doi.org/10.1111/j.1365-2648.2009.05165.x,PMC2861787,,,"AIM: This paper is a report of a study conducted to explore HIV healthcare services from the perspectives of both healthcare providers and patients in order to understand how to optimize HIV nursing care. BACKGROUND: In China, healthcare providers usually first diagnose HIV in a general hospital. Then, HIV-positive individuals are transferred to a specialist hospital. Between healthcare providers and healthcare institutions, there are many gaps in the process from diagnosis to treatment. METHODS: One focus group with 6 healthcare providers and 29 in-depth interviews with people living with HIV/AIDS were conducted during 2005. FINDINGS: Patients who were diagnosed with HIV in a general hospital often did not discuss their condition with a healthcare provider before being sent to a specialist hospital. Furthermore, since the patients had already been diagnosed, healthcare providers in the specialist hospital did not deal adequately with the disclosure process and emotional reactions to the diagnosis. They reported feeling overwhelmed in their role in providing healthcare services. Nurses reported that they were responsible for many “non-nursing” tasks and did not have the opportunity to give the type of care they were trained to offer. CONCLUSION: Optimizing HIV care in China will involve establishing clear boundaries between general and specialist hospitals and a division of labour among healthcare providers that eases the burden of care and takes advantage of the full scope of practice that nurses are trained to provide.",,"['Chen, Wei-Ti', 'Shiu, Cheng-Shi', 'Simoni, Jane', 'Fredriksen-Goldsen, Karen', 'Zhang, Fujie', 'Zhao, Hongxin']",,,,
,PMC,Asthma: Clinical Expression and Molecular Mechanisms,http://dx.doi.org/10.1016/j.jaci.2009.10.047,PMC2853245,,,"Asthma is a heterogenous disorder that is characterized by variable airflow obstruction, airway inflammation and hyperresponsiveness, and reversibility either spontaneously or as a result of treatment. Multiple etiologies no doubt exist for both its inception and symptom exacerbation once the disease is established. Factors underlying inception can range from viral respiratory tract infections in infancy(1,2) to occupational exposures in adults.(3) Factors underlying asthma exacerbations include allergen exposure in sensitized individuals, viral infections, exercise, irritants, ingestion of nonsteroidal anti-inflammatory agents, among others. Exacerbating factors may include one or all of these exposures, and vary both among and within patients. Asthma treatment is determined to a large extent following an initial assessment of severity and subsequent establishment of control, both of which can be variable over time and assessed in two domains: impairment (current) and risk (long term consequences).(4) Unfortunately, despite the availability of effective therapies, suboptimal asthma control exists in many patients on a world-wide basis.(5) The future development of novel therapies and treatment paradigms should address these disparities.",,"['Lemanske, Robert F.', 'Busse, William W.']",,,,
,PMC,QSAR Models for Predicting Cathepsin B Inhibition by Small Molecules: Continuous and Binary QSAR Models to Classify Cathepsin B Inhibition Activities of Small Molecules,http://dx.doi.org/10.1016/j.jmgm.2010.01.009,PMC2873115,,,"Cathepsin B is a potential target for the development of drugs to treat several important human diseases. A number of inhibitors targeting this protein have been developed in the past several years. Recently, a group of small molecules were identified to have inhibitory activity against cathepsin B through high throughput screening (HTS) tests. In this study, traditional continuous and binary QSAR models were built to classify the biological activities of previously identified compounds and to distinguish active compounds from inactive compounds for drug development based on the calculated molecular and physicochemical properties. Strong correlations were obtained for the continuous QSAR models with regression correlation coefficients (r(2)) and cross-validated correlation coefficients (q(2)) of 0.77 and 0.61 for all compounds, and 0.82 and 0.68 for the compound set excluding 3 outliers, respectively. The models were further validated through the leave-one-out (LOO) method and the training-test set method. The binary models demonstrated a strong level of predictability in distinguishing the active compounds from inactive compounds with accuracies of 0.89 and 0.94 for active and inactive compounds, respectively, in non-cross-validated models. Similar results were obtained for the cross-validated models. Collectively, these results demonstrate the models’ ability to discriminate between active and inactive compounds, suggesting that the models may be used to pre-screen compounds to facilitate compound optimization and to design novel inhibitors for drug development.",,"['Zhou, Zhigang', 'Wang, Yanli', 'Bryant, Stephen H.']",,,,
,PMC,"Distributions of HLA-A and -B alleles and haplotypes in the Yi ethnic minority of Yunnan, China: relationship to other populations",http://dx.doi.org/10.1631/jzus.B0900232,PMC2816316,,,"Objective: To investigate the distributions of human leukocyte antigen (HLA)-A and -B alleles and HLA-A-B haplotypes in the Yi ethnic minority of the Yunnan Province, situated in southwestern China. Methods: DNA typing for HLA-A and -B loci was performed using the polymerase chain reaction-sequence-based typing (PCR-SBT) method on 114 randomly selected healthy individuals of the Yi population. The allelic frequencies of HLA-A and -B loci were calculated by direct counting and HLA-A-B haplotypes were estimated using the expectation maximization algorithm. Results: A total of 17 HLA-A and 38 HLA-B alleles were found in the Yi population. The most frequent alleles were A*2402 (32.46%), A*1101 (26.32%), and A*0203 (10.09%) at the HLA-A locus and B*4601 (12.28%), B*1525 (10.09%), B*4001 (8.77%), and B*3802 (7.89%) at the HLA-B locus. The predominant HLA-A-B haplotypes were A*2402-B*1525 (7.86%) and A*0203-B*3802 (5.64%), followed by A*1101-B*4001 (4.69%). Phylogenetic analysis indicates that the Yi population in the Honghe, Yunnan Province of China basically belongs to groups of southeastern Asian origin, but shares some characteristics with northeastern Asian groups. Conclusion: The present study may add to the understanding of HLA polymorphism in the Yi ethnic group that was poorly defined previously, and provide useful information for bone marrow transplantation, anthropological research, and forensic sciences as well as for disease-association studies.",,"['Zhu, Bo-feng', 'Yang, Guang', 'Shen, Chun-mei', 'Qin, Hai-xia', 'Liu, Shun-zhi', 'Deng, Ya-jun', 'Fan, Shuan-liang', 'Deng, Li-bin', 'Chen, Feng', 'Zhang, Ping', 'Fang, Jie', 'Chen, Li-ping', 'Wang, Hong-dan', 'Wang, Zhen-yuan', 'Lucas, Rudolf']",,,,
,PMC,New Drugs/Drug News,,PMC2827919,,,,,,,,,
,PMC,Enzymatic and nonenzymatic functions of viral RNA-dependent RNA polymerases within oligomeric arrays,http://dx.doi.org/10.1261/rna.1955410,PMC2811667,,,"Few antivirals are effective against positive-strand RNA viruses, primarily because the high error rate during replication of these viruses leads to the rapid development of drug resistance. One of the favored current targets for the development of antiviral compounds is the active site of viral RNA-dependent RNA polymerases. However, like many subcellular processes, replication of the genomes of all positive-strand RNA viruses occurs in highly oligomeric complexes on the cytosolic surfaces of the intracellular membranes of infected host cells. In this study, catalytically inactive polymerases were shown to participate productively in functional oligomer formation and catalysis, as assayed by RNA template elongation. Direct protein transduction to introduce either active or inactive polymerases into cells infected with mutant virus confirmed the structural role for polymerase molecules during infection. Therefore, we suggest that targeting the active sites of polymerase molecules is not likely to be the best antiviral strategy, as inactivated polymerases do not inhibit replication of other viruses in the same cell and can, in fact, be useful in RNA replication complexes. On the other hand, polymerases that could not participate in functional RNA replication complexes were those that contained mutations in the amino terminus, leading to altered contacts in the folded polymerase and mutations in a known polymerase–polymerase interaction in the two-dimensional protein lattice. Thus, the functional nature of multimeric arrays of RNA-dependent RNA polymerase supplies a novel target for antiviral compounds and provides a new appreciation for enzymatic catalysis on membranous surfaces within cells.",,"['Spagnolo, Jeannie F.', 'Rossignol, Evan', 'Bullitt, Esther', 'Kirkegaard, Karla']",,,,
,PMC,OAS single-nucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine,http://dx.doi.org/10.1016/j.humimm.2010.01.004,PMC2842477,,,"Interferon (IFN)-induced antiviral genes are crucial players in innate antiviral defense and potential determinants of immune response heterogeneity. We selected 114 candidate SNPs from 12 antiviral genes using an LD tagSNP selection approach and genotyped them in a cohort of 738 schoolchildren immunized with two doses of rubella vaccine. Associations between SNPs/haplotypes and rubella virus-specific immune measures were assessed using linear regression methodologies. We identified 23 significant associations (p<0.05) between polymorphisms within the 2′-5′-oligoadenylate synthetase (OAS) gene cluster, and rubella virus-specific IL-2, IL-10, IL-6 secretion and antibody levels. The minor allele variants of three OAS1 SNPs (rs3741981/Ser162Gly, rs1051042/Thr361Arg, rs2660), located in a linkage disequilibrium block of functional importance, were significantly associated with an increase in rubella virus-specific IL-2/Th1 response (p≤0.024). Seven OAS1 and OAS3 promoter/regulatory SNPs were similarly associated with IL-2 secretion. Importantly, two SNPs (rs3741981 and rs10774670), independently cross-regulated rubella virus-specific IL-10 secretion levels (p≤0.031). Furthermore, both global tests and individual haplotype analyses revealed significant associations between OAS1 haplotypes and rubella virus-specific cytokine secretion. Our results suggest that innate immunity and OAS genetic variations are likely involved in modulating the magnitude and quality of the adaptive immune responses to live attenuated rubella vaccine.",,"['Haralambieva, Iana H.', 'Dhiman, Neelam', 'Ovsyannikova, Inna G.', 'Vierkant, Robert A.', 'Pankratz, V. Shane', 'Jacobson, Robert M.', 'Poland, Gregory A.']",,,,
,PMC,Nosocomial Outbreak of Serious Canine Infectious Tracheobronchitis (Kennel Cough) Caused by Canine Herpesvirus Infection,http://dx.doi.org/10.1128/JCM.02128-09,PMC2849577,,,"Canine herpesvirus (CHV; Canid herpesvirus 1) is principally a perinatal pathogen of pregnant bitches and newborn pups and secondarily a respiratory tract pathogen of older pups and dogs. Infectious disease of the canine respiratory tract frequently occurs among dogs in groups, in which it is called “ infectious tracheobronchitis” (ITB). Mortality from ITB is generally negligible, and the clinical importance of CHV as an ITB pathogen is considered to be low. The present report describes a novel ITB outbreak accompanied by death among aged dogs in an animal medical center. Most inpatient dogs had received medications that could induce immunosuppression. CHV was the only pathogen identified, and several CHV isolates were recovered in cell culture. No other viral pathogens or significant bacterial pathogens were found. Molecular and serological analyses revealed that the causative CHV isolates were from a single source but that none was a peculiar strain when the strains were compared with previous CHV strains. The virus had presumably spread among the dogs predisposed to infection in the center. The present results serve as a warning to canine clinics that, under the specific set of circumstances described, such serious CHV outbreaks may be expected wherever canine ITB occurs.",,"['Kawakami, Kazuo', 'Ogawa, Hiroyuki', 'Maeda, Ken', 'Imai, Ayako', 'Ohashi, Emi', 'Matsunaga, Satoru', 'Tohya, Yukinobu', 'Ohshima, Takahisa', 'Mochizuki, Masami']",,,,
,PMC,Isolation of an Infectious Endogenous Retrovirus in a Proportion of Live Attenuated Vaccines for Pets,http://dx.doi.org/10.1128/JVI.02715-09,PMC2838105,,,"The genomes of all animal species are colonized by endogenous retroviruses (ERVs). Although most ERVs have accumulated defects that render them incapable of replication, fully infectious ERVs have been identified in various mammals. In this study, we isolated a feline infectious ERV (RD-114) in a proportion of live attenuated vaccines for pets. Isolation of RD-114 was made in two independent laboratories using different detection strategies and using vaccines for both cats and dogs commercially available in Japan or the United Kingdom. This study shows that the methods currently employed to screen veterinary vaccines for retroviruses should be reevaluated.",,"['Miyazawa, Takayuki', 'Yoshikawa, Rokusuke', 'Golder, Matthew', 'Okada, Masaya', 'Stewart, Hazel', 'Palmarini, Massimo']",,,,
,PMC,The N-Terminal Region of Severe Acute Respiratory Syndrome Coronavirus Protein 6 Induces Membrane Rearrangement and Enhances Virus Replication,http://dx.doi.org/10.1128/JVI.02570-09,PMC2838104,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) accessory protein 6 (p6) is a 63-amino-acid multifunctional Golgi-endoplasmic reticulum (ER) membrane-associated protein, with roles in enhancing virus replication and in evading the innate immune response to infection by inhibiting STAT1 (signal transducer and activator of transcription factor 1) translocation to the nucleus. Here, we demonstrate that p6 has an N-terminal region-cytoplasm-C-terminal region-cytoplasm configuration with residues 2 to 37 likely membrane embedded. Expression of p6, or of its N-terminal 41-amino-acid region, in the absence of other viral proteins, induced the formation of membranous structures, some of which were similar to double membrane vesicles involved in virus replication. Consistent with a role in virus replication, p6 partially colocalized with nonstructural protein 3 (nsp3), a marker for virus replication complexes. Further, while the C-terminal region is required for preventing STAT1 translocation to the nucleus, our results also indicated that the N-terminal 18 amino acids were necessary for maximal inhibition. Collectively, these results support the notion that p6 is a two-domain protein, although the function of each is not completely independent of the other.",,"['Zhou, Haixia', 'Ferraro, Debra', 'Zhao, Jincun', 'Hussain, Snawar', 'Shao, Jianqiang', 'Trujillo, Jonathan', 'Netland, Jason', 'Gallagher, Thomas', 'Perlman, Stanley']",,,,
,PMC,Immunization with an Attenuated Severe Acute Respiratory Syndrome Coronavirus Deleted in E Protein Protects Against Lethal Respiratory Disease,http://dx.doi.org/10.1016/j.virol.2010.01.004,PMC2830353,,,"The Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) caused substantial morbidity and mortality in 2002-2003. Deletion of the envelope (E) protein modestly diminished virus growth in tissue culture but abrogated virulence in animals. Here, we show that immunization with rSARS-CoV-ΔE or SARS-CoV-Δ[E,6-9b] (deleted in accessory proteins (6,7a,7b,8a,8b,9b) in addition to E) nearly completely protected BALB/c mice from fatal respiratory disease caused by mouse-adapted SARS-CoV and partly protected hACE2 Tg mice from lethal disease. hACE2 Tg mice, which express the human SARS-CoV receptor, are extremely susceptible to infection. We also show that rSARS-CoV-ΔE and rSARS-CoV-Δ[E,6-9b] induced anti-virus T cell and antibody responses. Further, the E-deleted viruses were stable after 16 blind passages through tissue culture cells, with only a single mutation in the surface glycoprotein detected. The passaged virus remained avirulent in mice. These results suggest that rSARS-CoV-ΔE is an efficacious vaccine candidate that might be useful if SARS recurred.",,"['Netland, Jason', 'DeDiego, Marta L.', 'Zhao, Jincun', 'Fett, Craig', 'Álvarez, Enrique', 'Nieto-Torres, José L.', 'Enjuanes, Luis', 'Perlman, Stanley']",,,,
,PMC,Apolipoprotein D: An overview of its role in aging and age-related diseases,,PMC3691099,,,"“It’s got to be doing something important!” —Seymour Benzer, reflecting on the observation that ApoD mRNA levels increase 500-fold following neuronal crush injury. Seymour Benzer’s curiosity was legendary and seemingly limitless.(1-5) Towards the end of his life, one of the (many) questions that kept him awake at night concerned the emerging role of Apolipoprotein D (ApoD) in aging and neurological disease. In this perspective, we will discuss the clinical and biochemical data on ApoD, and the input from the recent genetic studies in model systems, including those from the Benzer lab.",,"['Muffat, Julien', 'Walker, David W.']",,,,
,PMC,Using 3 TLR ligands as a combination adjuvant induces qualitative changes                in T cell responses needed for antiviral protection in mice,http://dx.doi.org/10.1172/JCI39293,PMC2811160,,,"TLR ligands are promising candidates for the development of novel vaccine adjuvants that can elicit protective immunity against emerging infectious diseases. Adjuvants have been used most frequently to increase the quantity of an immune response. However, the quality of a T cell response can be more important than its quantity. Stimulating certain pairs of TLRs induces a synergistic response in terms of activating dendritic cells and eliciting/enhancing T cell responses through clonal expansion, which increases the number of responding T cells. Here, we have found that utilizing ligands for 3 TLRs (TLR2/6, TLR3, and TLR9) greatly increased the protective efficacy of vaccination with an HIV envelope peptide in mice when compared with using ligands for only any 2 of these TLRs; surprisingly, increased protection was induced without a marked increase in the number of peptide-specific T cells. Rather, the combination of these 3 TLR ligands augmented the quality of the T cell responses primarily by amplifying their functional avidity for the antigen, which was necessary for clearance of virus. The triple combination increased production of DC IL-15 along with its receptor, IL-15Rα, which contributed to high avidity, and decreased expression of programmed death–ligand 1 and induction of Tregs. Therefore, selective TLR ligand combinations can increase protective efficacy by increasing the quality rather than the quantity of T cell responses.",,"['Zhu, Qing', 'Egelston, Colt', 'Gagnon, Susan', 'Sui, Yongjun', 'Belyakov, Igor M.', 'Klinman, Dennis M.', 'Berzofsky, Jay A.']",,,,
,PMC,LDH Concentration in Nasal-Wash Fluid as a Biochemical Predictor of Bronchiolitis Severity,http://dx.doi.org/10.1542/peds.2009-0411,PMC3050005,,,"OBJECTIVE: Because the decision to hospitalize an infant with bronchiolitis is often supported by subjective criteria and objective indicators of bronchiolitis severity are lacking, we tested the hypothesis that lactate dehydrogenase (LDH), which is released from injured cells, is a useful biochemical indicator of bronchiolitis severity. PATIENTS AND METHODS: We retrospectively analyzed a study of children <24 months old presenting to the emergency department with bronchiolitis. Demographic, clinical information, nasal-wash (NW) and serum specimens were obtained. NW samples were analyzed for respiratory viruses, caspase 3/7 activity and a panel of cytokines and chemokines. Total LDH activity was tested in NW samples and sera. RESULTS: Of 101 enrolled children (median age, 5.6 months), 98 had NW specimens available. A viral etiology was found in 82 patients (83.6%), with respiratory syncytial virus (RSV) (66%) and rhinovirus (19%) being the most common viruses detected. Concentrations of LDH in NW specimens were independent from those in sera, and were higher in children with RSV infection or with dual infection. Significant correlations were found between NW LDH and NW cytokines/chemokines. Similarly, NW LDH correlated with NW-caspase 3/7 activity (r=0.75; P<.001). In a multivariate analysis, NW LDH concentration in the upper quartile was significantly associated with a reduced risk of hospitalization (odds ratio: 0.19; 95% confidence interval: 0.05–0.68; P=0.011). CONCLUSIONS: NW LDH levels in young children with bronchiolitis varied according to viral etiology and disease severity. Values in the upper quartile were associated with ~80% risk reduction in hospitalization, likely reflecting a robust antiviral response. NW LDH may be a useful biomarker to assist the clinician in the decision to hospitalize a child with bronchiolitis.",,"['Laham, Federico R.', 'Trott, Amanda A.', 'Bennett, Berkeley L.', 'Kozinetz, Claudia A.', 'Jewell, Alan M.', 'Garofalo, Roberto P.', 'Piedra, Pedro A.']",,,,
,PMC,Evidence for ribosomal frameshifting and a novel overlapping gene in the genomes of insect-specific flaviviruses,http://dx.doi.org/10.1016/j.virol.2009.12.033,PMC2830293,,,"Flaviviruses have a positive-sense, single-stranded RNA genome of ∼11 kb, encoding a large polyprotein that is cleaved to produce ∼10 mature proteins. Cell fusing agent virus, Kamiti River virus, Culex flavivirus and several recently discovered flaviviruses have no known vertebrate host and apparently infect only insects. We present compelling bioinformatic evidence for a 253-295 codon overlapping gene (designated fifo) conserved throughout these insect-specific flaviviruses, and immunofluorescent detection of its product. Fifo overlaps the NS2A/NS2B coding sequence in the -1/+2 reading frame and is most likely expressed as a trans-frame fusion protein via ribosomal frameshifting at a conserved GGAUUUY slippery heptanucleotide with 3′-adjacent RNA secondary structure (which stimulates efficient frameshifting in vitro). The discovery bears striking parallels to the recently discovered ribosomal frameshifting site in the NS2A coding sequence of the Japanese encephalitis serogroup of flaviviruses, and suggests that programmed ribosomal frameshifting may be more widespread in flaviviruses than currently realized.",,"['Firth, Andrew E', 'Blitvich, Bradley J', 'Wills, Norma M', 'Miller, Cathy L', 'Atkins, John F']",,,,
,PMC,Correspondence (letter to the editor): How Up to Date Was This Information?,http://dx.doi.org/10.3238/arztebl.2010.0037a,PMC2816789,,,,,"Gürtler, Lutz",,,,
,PMC,Exercise training normalizes ACE and ACE2 in the brain of rabbits with pacing-induced heart failure,http://dx.doi.org/10.1152/japplphysiol.00840.2009,PMC2853198,,,"Exercise training (EX) normalizes sympathetic outflow and plasma ANG II in chronic heart failure (CHF). The central mechanisms by which EX reduces this sympathoexcitatory state are unclear, but EX may alter components of the brain renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE) may mediate an increase in sympathetic nerve activity (SNA). ACE2 metabolizes ANG II to ANG-(1–7), which may have antagonistic effects to ANG II. Little is known concerning the regulation of ACE and ACE2 in the brain and the effect of EX on these enzymes, especially in the CHF state. This study aimed to investigate the effects of EX on the regulation of ACE and ACE2 in the brain in an animal model of CHF. We hypothesized that the ratio of ACE to ACE2 would increase in CHF and would be reduced by EX. Experiments were performed on New Zealand White rabbits divided into the following groups: sham, sham + EX, CHF, and CHF + EX (n = 5 rabbits/group). The cortex, cerebellum, medulla, hypothalamus, paraventricular nucleus (PVN), nucleus tractus solitarii (NTS), and rostral ventrolateral medulla (RVLM) were analyzed. ACE protein and mRNA expression in the cerebellum, medulla, hypothalamus, PVN, NTS, and RVLM were significantly upregulated in CHF rabbits (ratio of ACE to GAPDH: 0.3 ± 0.03 to 0.8 ± 0.10 in the RVLM, P < 0.05). EX normalized this upregulation compared with CHF (0.8 ± 0.1 to 0.4 ± 0.1 in the RVLM). ACE2 protein and mRNA expression decreased in CHF (ratio of ACE2 to GAPDH: 0.3 ± 0.02 to 0.1 ± 0.01 in the RVLM). EX increased ACE2 expression compared with CHF (0.1 ± 0.01 to 0.8 ± 0.1 in the RVLM). ACE2 was present in the cytoplasm of neurons and ACE in endothelial cells. These data suggest that the activation of the central RAS in animals with CHF involves an imbalance of ACE and ACE2 in regions of the brain that regulate autonomic function and that EX can reverse this imbalance.",,"['Kar, Sumit', 'Gao, Lie', 'Zucker, Irving H.']",,,,
,PMC,Small-angle scattering for structural biology—Expanding the frontier while avoiding the pitfalls,http://dx.doi.org/10.1002/pro.351,PMC2867006,,,"The last decade has seen a dramatic increase in the use of small-angle scattering for the study of biological macromolecules in solution. The drive for more complete structural characterization of proteins and their interactions, coupled with the increasing availability of instrumentation and easy-to-use software for data analysis and interpretation, is expanding the utility of the technique beyond the domain of the biophysicist and into the realm of the protein scientist. However, the absence of publication standards and the ease with which 3D models can be calculated against the inherently 1D scattering data means that an understanding of sample quality, data quality, and modeling assumptions is essential to have confidence in the results. This review is intended to provide a road map through the small-angle scattering experiment, while also providing a set of guidelines for the critical evaluation of scattering data. Examples of current best practice are given that also demonstrate the power of the technique to advance our understanding of protein structure and function.",,"['Jacques, David A', 'Trewhella, Jill']",,,,
,PMC,Influenza Virus Inactivation for Studies of Antigenicity and Phenotypic Neuraminidase Inhibitor Resistance Profiling,http://dx.doi.org/10.1128/JCM.02045-09,PMC2832438,,,"Introduction of a new influenza virus in humans urges quick analysis of its virological and immunological characteristics to determine the impact on public health and to develop protective measures for the human population. At present, however, the necessity of executing pandemic influenza virus research under biosafety level 3 (BSL-3) high-containment conditions severely hampers timely characterization of such viruses. We tested heat, formalin, Triton X-100, and β-propiolactone treatments for their potencies in inactivating human influenza A(H3N2) and avian A(H7N3) viruses, as well as seasonal and pandemic A(H1N1) virus isolates, while allowing the specimens to retain their virological and immunological properties. Successful heat inactivation coincided with the loss of hemagglutinin (HA) and neuraminidase (NA) characteristics, and β-propiolactone inactivation reduced the hemagglutination titer and NA activity of the human influenza virus 10-fold or more. Although Triton X-100 treatment resulted in inconsistent HA activity, the NA activities in culture supernatants were enhanced consistently. Nonetheless, formalin treatment permitted the best retention of HA and NA properties. Triton X-100 treatment proved to be the easiest-to-use influenza virus inactivation protocol for application in combination with phenotypic NA inhibitor susceptibility assays, while formalin treatment preserved B-cell and T-cell epitope antigenicity, allowing the detection of both humoral and cellular immune responses. In conclusion, we demonstrated successful influenza virus characterization using formalin- and Triton X-100-inactivated virus samples. Application of these inactivation protocols limits work under BSL-3 conditions to virus culture, thus enabling more timely determination of public health impact and development of protective measures when a new influenza virus, e.g., pandemic A(H1N1)v virus, is introduced in humans.",,"['Jonges, Marcel', 'Liu, Wai Ming', 'van der Vries, Erhard', 'Jacobi, Ronald', 'Pronk, Inge', 'Boog, Claire', 'Koopmans, Marion', 'Meijer, Adam', 'Soethout, Ernst']",,,,
,PMC,"Host Range, Prevalence, and Genetic Diversity of Adenoviruses in Bats",http://dx.doi.org/10.1128/JVI.02497-09,PMC2849498,,,"Bats are the second largest group of mammals on earth and act as reservoirs of many emerging viruses. In this study, a novel bat adenovirus (AdV) (BtAdV-TJM) was isolated from bat fecal samples by using a bat primary kidney cell line. Infection studies indicated that most animal and human cell lines are susceptible to BtAdV-TJM, suggesting a possible wide host range. Genome analysis revealed 30 putative genes encoding proteins homologous to their counterparts in most known AdVs. Phylogenetic analysis placed BtAdV-TJM within the genus Mastadenovirus, most closely related to tree shrew and canine AdVs. PCR analysis of 350 bat fecal samples, collected from 19 species in five Chinese provinces during 2007 and 2008, indicated that 28 (or 8%) samples were positive for AdVs. The samples were from five bat species, Hipposideros armiger, Myotis horsfieldii, M. ricketti, Myotis spp., and Scotophilus kuhlii. The prevalence ranged from 6.25% (H. armiger in 2007) to 40% (M. ricketti in 2007). Comparison studies based on available partial sequences of the pol gene demonstrated a great genetic diversity among bat AdVs infecting different bat species as well as those infecting the same bat species. This is the first report of a genetically diverse group of DNA viruses in bats. Our results support the notion, derived from previous studies based on RNA viruses (especially coronaviruses and astroviruses), that bats seem to have the unusual ability to harbor a large number of genetically diverse viruses within a geographic location and/or within a taxonomic group.",,"['Li, Yan', 'Ge, Xingyi', 'Zhang, Huajun', 'Zhou, Peng', 'Zhu, Yan', 'Zhang, Yunzhi', 'Yuan, Junfa', 'Wang, Lin-Fa', 'Shi, Zhengli']",,,,
,PMC,Hepatitis B Virus (HBV) Surface Antigen Interacts with and Promotes Cyclophilin A Secretion: Possible Link to Pathogenesis of HBV Infection,http://dx.doi.org/10.1128/JVI.02555-09,PMC2838095,,,"Cyclophilin A (CypA), predominantly located intracellularly, is a multifunctional protein. We previously reported decreased CypA levels in hepatocytes of transgenic mice expressing hepatitis B virus (HBV) surface antigen (HBsAg). In this study, we found that expression of HBV small surface protein (SHBs) in human hepatoma cell lines specifically triggered CypA secretion, whereas SHBs added extracellularly to culture medium did not. Moreover, CypA secretion was not promoted by the expression of a secretion deficient SHBs mutant, suggesting a close association between secretion of CypA and SHBs. Interaction between CypA and SHBs was observed by using coimmunoprecipitation and glutathione S-transferase pull-down assays. Hydrodynamic injection of the SHBs expression construct into C57BL/6J mice resulted in increased serum CypA levels and ALT/AST levels, as well as the infiltration of inflammatory cells surrounding SHBs-positive hepatocytes. The inflammatory response and serum ALT/AST level were reduced when the chemotactic effect of CypA was inhibited by cyclosporine and anti-CD147 antibody. Furthermore, higher serum CypA levels were detected in chronic hepatitis B patients than in healthy individuals. In HBV patients who had received liver transplantation, serum CypA levels declined dramatically after the loss of HBsAg as a consequence of liver transplantation. Taken together, these results indicate that expression and secretion of SHBs can promote CypA secretion, which may contribute to the pathogenesis of HBV infection.",,"['Tian, Xiaochen', 'Zhao, Chao', 'Zhu, Hongguang', 'She, Weimin', 'Zhang, Jiming', 'Liu, Jing', 'Li, Lanjuan', 'Zheng, Shusen', 'Wen, Yu-Mei', 'Xie, Youhua']",,,,
,PMC,A Lectin Isolated from Bananas Is a Potent Inhibitor of HIV Replication,http://dx.doi.org/10.1074/jbc.M109.034926,PMC2838287,,,"BanLec is a jacalin-related lectin isolated from the fruit of bananas, Musa acuminata. This lectin binds to high mannose carbohydrate structures, including those found on viruses containing glycosylated envelope proteins such as human immunodeficiency virus type-1 (HIV-1). Therefore, we hypothesized that BanLec might inhibit HIV-1 through binding of the glycosylated HIV-1 envelope protein, gp120. We determined that BanLec inhibits primary and laboratory-adapted HIV-1 isolates of different tropisms and subtypes. BanLec possesses potent anti-HIV activity, with IC(50) values in the low nanomolar to picomolar range. The mechanism for BanLec-mediated antiviral activity was investigated by determining if this lectin can directly bind the HIV-1 envelope protein and block entry of the virus into the cell. An enzyme-linked immunosorbent assay confirmed direct binding of BanLec to gp120 and indicated that BanLec can recognize the high mannose structures that are recognized by the monoclonal antibody 2G12. Furthermore, BanLec is able to block HIV-1 cellular entry as indicated by temperature-sensitive viral entry studies and by the decreased levels of the strong-stop product of early reverse transcription seen in the presence of BanLec. Thus, our data indicate that BanLec inhibits HIV-1 infection by binding to the glycosylated viral envelope and blocking cellular entry. The relative anti-HIV activity of BanLec compared favorably to other anti-HIV lectins, such as snowdrop lectin and Griffithsin, and to T-20 and maraviroc, two anti-HIV drugs currently in clinical use. Based on these results, BanLec is a potential component for an anti-viral microbicide that could be used to prevent the sexual transmission of HIV-1.",,"['Swanson, Michael D.', 'Winter, Harry C.', 'Goldstein, Irwin J.', 'Markovitz, David M.']",,,,
,PMC,"THE IL-6 (−174, C/C) GENOTYPE PREDICTS GREATER RHINOVIRUS ILLNESS",http://dx.doi.org/10.1086/649559,PMC2943745,,,"INTRODUCTION: In adults and children with RSV infection, a polymorphism in the IL-6 promoter at position −174 predicted illness magnitude. Also, polymorphisms in the IL-10, TNFα and INFγ genes were associated with immune responsiveness and the frequency of complications. Here, the effect of these polymorphisms on illness and seroconversion during infection with rhinovirus type 39 (RV39) was evaluated. METHODS: Seventy-two adults were genotyped for the selected polymorphisms, experimentally exposed to RV39 and followed for infection, seroconversion and symptoms/signs of illness. Regression analysis was used to determine if these polymorphisms predicted seroconversion and illness magnitude in 57 infected subjects. RESULTS: The low production IL-6 (−174, C/C) phenotype was associated with greater symptom magnitudes and the INFγ (+874) phenotype predicted the frequency of seroconversion. No relationship between the IL-10 or TNFα polymorphisms and any measured outcome was documented. IL-6 protein measured in nasal wash fluids of 51 subjects was positively correlated with symptom magnitude but was independent of the IL-6 (−174) genotypes representing high and low production phenotypes. CONCLUSIONS: These results document significant associations between the IL-6 (−174) and INFγ (+874) gene polymorphisms and specific responses to experimental RV39 infection. For the IL-6 (−174) polymorphism, the results replicate those for RSV infection.",,"['Doyle, William J.', 'Casselbrant, Margaretha L.', 'Li-Korotky, Ha-Sheng', 'Cullen Doyle, Allison P.', 'Lo, Chia-Yee', 'Turner, Ronald', 'Cohen, Sheldon']",,,,
,PMC,How the non-inflammasome NLRs function in the innate immune system,http://dx.doi.org/10.1126/science.1184004,PMC3943909,,,"NLR (nucleotide-binding domain, leucine-rich repeat containing) proteins have rapidly emerged as central regulators of immunity and inflammation with demonstrated relevance to human diseases. Much attention has focused on the ability of several NLRs to activate the inflammasome complex and drive proteolytic processing of inflammatory cytokines; however, NLRs also regulate important inflammasome-independent functions in the immune system. In this review, we will discuss several of these functions, including the regulation of canonical and non-canonical NF-κB activation, MAP kinase activation, cytokine and chemokine production, antimicrobial reactive oxygen species production, type I interferon production, and RNase L activity. We will also explore the mechanistic basis of these functions and present current challenges in the field.",,"['Ting, Jenny P.Y.', 'Duncan, Joseph A.', 'Lei, Yu']",,,,
,PMC,Stefin B Interacts with Histones and Cathepsin L in the Nucleus,http://dx.doi.org/10.1074/jbc.M109.034793,PMC2843170,,,"Stefin B (cystatin B) is an endogenous inhibitor of cysteine proteinases localized in the nucleus and the cytosol. Loss-of-function mutations in the stefin B gene (CSTB) gene were reported in patients with Unverricht-Lundborg disease (EPM1). We have identified an interaction between stefin B and nucleosomes, specifically with histones H2A.Z, H2B, and H3. In synchronized T98G cells, stefin B co-immunoprecipitated with histone H3, predominantly in the G(1) phase of the cell cycle. Stefin B-deficient mouse embryonic fibroblasts entered S phase earlier than wild type mouse embryonic fibroblasts. In contrast, increased expression of stefin B in the nucleus delayed cell cycle progression in T98G cells. The delay in cell cycle progression was associated with the inhibition of cathepsin L in the nucleus, as judged from the decreased cleavage of the CUX1 transcription factor. In vitro, inhibition of cathepsin L by stefin B was potentiated in the presence of histones, whereas histones alone did not affect the cathepsin L activity. Interaction of stefin B with the Met-75 truncated form of cathepsin L in the nucleus was confirmed by fluorescence resonance energy transfer experiments in the living cells. Stefin B could thus play an important role in regulating the proteolytic activity of cathepsin L in the nucleus, protecting substrates such as transcription factors from its proteolytic processing.",,"['Čeru, Slavko', 'Konjar, Špela', 'Maher, Katarina', 'Repnik, Urška', 'Križaj, Igor', 'Benčina, Mojca', 'Renko, Miha', 'Nepveu, Alain', 'Žerovnik, Eva', 'Turk, Boris', 'Kopitar-Jerala, Nataša']",,,,
,PMC,Identification of Novel Diagnostic Serum Biomarkers for Chagas' Disease in Asymptomatic Subjects by Mass Spectrometric Profiling,http://dx.doi.org/10.1128/JCM.02207-09,PMC2849606,,,"More than 10 million people are thought to be infected with Trypanosoma cruzi, primarily in the Americas. The clinical manifestations of Chagas' disease (CD) are variable, but most subjects remain asymptomatic for decades. Only 15 to 30% eventually develop terminal complications. All current diagnostic tests have limitations. New approaches are needed for blood bank screening as well as for improved diagnosis and prognosis. Sera from subjects with asymptomatic CD (n = 131) were compared to those from uninfected controls (n = 164) and subjects with other parasitic diseases (n = 140), using protein array mass spectrometry. To identify biomarkers associated with CD, sera were fractionated by anion-exchange chromatography and bound to two commercial ProteinChip array chemistries: WCX2 and IMAC3. Multiple candidate biomarkers were found in CD sera (3 to 75.4 kDa). Algorithms employing 3 to 5 of these biomarkers achieved up to 100% sensitivity and 98% specificity for CD. The biomarkers most useful for diagnosis were identified and validated. These included MIP1 alpha, C3a anaphylatoxin, and unusually truncated forms of fibronectin, apolipoprotein A1 (ApoA1), and C3. An antipeptide antiserum against the 28.9-kDa C terminus of the fibronectin fragment achieved good specificity (90%) for CD in a Western blot format. We identified full-length ApoA1 (28.1 kDa), the major structural and functional protein component of high-density lipoprotein (HDL), as an important negative biomarker for CD, and relatively little full-length ApoA1 was detected in CD sera. This work provides proof of principle that both platform-dependent (i.e., mass spectrometry-based) and platform-independent (i.e., Western blot) tests can be generated using high-throughput mass profiling.",,"['Ndao, Momar', 'Spithill, Terry W.', 'Caffrey, Rebecca', 'Li, Hongshan', 'Podust, Vladimir N.', 'Perichon, Regis', 'Santamaria, Cynthia', 'Ache, Alberto', 'Duncan, Mark', 'Powell, Malcolm R.', 'Ward, Brian J.']",,,,
,PMC,NTPase and 5′ to 3′ RNA Duplex-Unwinding Activities of the Hepatitis E Virus Helicase Domain,http://dx.doi.org/10.1128/JVI.02130-09,PMC2838093,,,"Hepatitis E virus (HEV) is a causative agent of acute hepatitis, and it is the sole member of the genus Hepevirus in the family Hepeviridae. The open reading frame 1 (ORF1) protein of HEV encodes nonstructural polyprotein with putative domains for methyltransferase, cysteine protease, helicase and RNA-dependent RNA polymerase. It is not yet known whether ORF1 functions as a single protein with multiple domains or is processed to form separate functional units. On the basis of amino acid conserved motifs, HEV helicase has been grouped into helicase superfamily 1 (SF-1). In order to examine the RNA helicase activity of the NTPase/helicase domain of HEV, the region (amino acids 960 to 1204) was cloned and expressed as histidine-tagged protein in Escherichia coli (HEV Hel) and purified. HEV Hel exhibited NTPase and RNA unwinding activities. Enzyme hydrolyzed all rNTPs efficiently, dATP and dCTP with moderate efficiency, while it showed less hydrolysis of dGTP and dTTP. Enzyme showed unwinding of only RNA duplexes with 5′ overhangs showing 5′-to-3′ polarity. We also expressed and purified two HEV Hel mutants. Helicase mutant I, with substitution in the nucleotide-binding motif I (GKS to GAS), showed 30% ATPase activity. Helicase mutant II, with substitutions in the Mg(2+) binding motif II (DEAP to AAAP), showed 50% ATPase activity. Both mutants completely lost ability to unwind RNA duplexes with 5′ overhangs. These findings represent the first report demonstrating NTPase/RNA helicase activity of the helicase domain of HEV ORF1.",,"['Karpe, Yogesh A.', 'Lole, Kavita S.']",,,,
,PMC,"Ecoepidemiology and Complete Genome Comparison of Different Strains of Severe Acute Respiratory Syndrome-Related Rhinolophus Bat Coronavirus in China Reveal Bats as a Reservoir for Acute, Self-Limiting Infection That Allows Recombination Events",http://dx.doi.org/10.1128/JVI.02219-09,PMC2826035,,,"Despite the identification of severe acute respiratory syndrome-related coronavirus (SARSr-CoV) in Rhinolophus Chinese horseshoe bats (SARSr-Rh-BatCoV) in China, the evolutionary and possible recombination origin of SARSr-CoV remains undetermined. We carried out the first study to investigate the migration pattern and SARSr-Rh-BatCoV genome epidemiology in Chinese horseshoe bats during a 4-year period. Of 1,401 Chinese horseshoe bats from Hong Kong and Guangdong, China, that were sampled, SARSr-Rh-BatCoV was detected in alimentary specimens from 130 (9.3%) bats, with peak activity during spring. A tagging exercise of 511 bats showed migration distances from 1.86 to 17 km. Bats carrying SARSr-Rh-BatCoV appeared healthy, with viral clearance occurring between 2 weeks and 4 months. However, lower body weights were observed in bats positive for SARSr-Rh-BatCoV, but not Rh-BatCoV HKU2. Complete genome sequencing of 10 SARSr-Rh-BatCoV strains showed frequent recombination between different strains. Moreover, recombination was detected between SARSr-Rh-BatCoV Rp3 from Guangxi, China, and Rf1 from Hubei, China, in the possible generation of civet SARSr-CoV SZ3, with a breakpoint at the nsp16/spike region. Molecular clock analysis showed that SARSr-CoVs were newly emerged viruses with the time of the most recent common ancestor (tMRCA) at 1972, which diverged between civet and bat strains in 1995. The present data suggest that SARSr-Rh-BatCoV causes acute, self-limiting infection in horseshoe bats, which serve as a reservoir for recombination between strains from different geographical locations within reachable foraging range. Civet SARSr-CoV is likely a recombinant virus arising from SARSr-CoV strains closely related to SARSr-Rh-BatCoV Rp3 and Rf1. Such frequent recombination, coupled with rapid evolution especially in ORF7b/ORF8 region, in these animals may have accounted for the cross-species transmission and emergence of SARS.",,"['Lau, Susanna K. P.', 'Li, Kenneth S. M.', 'Huang, Yi', 'Shek, Chung-Tong', 'Tse, Herman', 'Wang, Ming', 'Choi, Garnet K. Y.', 'Xu, Huifang', 'Lam, Carol S. F.', 'Guo, Rongtong', 'Chan, Kwok-Hung', 'Zheng, Bo-Jian', 'Woo, Patrick C. Y.', 'Yuen, Kwok-Yung']",,,,
,PMC,Synthesis and in vitro evaluation of cyclic NGR peptide targeted thermally sensitive liposome,http://dx.doi.org/10.1016/j.jconrel.2009.12.031,PMC2847670,,,"The Asn-Gly-Arg (NGR) motif in both cyclic and linear form has previously been shown to specifically bind to CD13/aminopeptidase N that is selectively overexpressed in tumor vasculature and some tumor cells. However, previous versions of cyclic NGR used a liable disulfide bridge between cysteine residues that may be problematic for liposome targeting due to disulfide bond formation between adjacent peptides on the liposomal surface. In this study, we report the design, synthesis, and characterization of a novel cyclic NGR containing peptide, cKNGRE, which does not contain a disulfide bridge. cKNGRE was synthesized in good yield and purity and attached to the fluorescent reporter Oregon Green (cKNGRE-OG) and lysolipid-containing temperature sensitive liposome (LTSLs). The identity of cKNGRE was verified with NMR and mass spectral techniques. In vitro fluorescence microscopy evaluation of cKNGRE-OG demonstrated binding and active uptake by CD13(+) cancer cells and minimal binding to CD13(−) cancer cells. The cKNGRE-OG ligand displayed 3.6-fold greater affinity for CD13(+) cancer cells than a linear NGR containing peptide. Affinity for CD13(+) cancer cells was similarly improved 10-fold for both the cyclic and linear NGR when presented in a multivalent fashion on the surface of an LTSL. cKNGRE-targeted LTSLs rapidly released (>75% in <4 sec) doxorubicin at 41.3°C with minimal release at 37°C. These results demonstrate the ability to synthesize a cKNGRE-targeted temperature sensitive liposome that lacks a disulfide bridge and has sufficient binding affinity for biological applications.",,"['Negussie, Ayele H.', 'Miller, Jenna L.', 'Reddy, Goutham', 'Drake, Steven K.', 'Wood, Bradford J.', 'Dreher, Matthew R.']",,,,
,PMC,Capacity of serotype 19A and 15B/C Streptococcus pneumoniae isolates for experimental otitis media: implications for the conjugate vaccine,http://dx.doi.org/10.1016/j.vaccine.2009.12.078,PMC2851619,,,"Non-vaccine Streptococcus pneumoniae serotypes are increasingly associated with disease. We evaluated isolates of the same sequence type (ST199) but different serotype (15B/C, 19A) for growth in vitro, and pathogenic potential in a chinchilla otitis media model. We also developed a qPCR assay to quantitatively assess each isolate, circumventing the need for selectable markers. In vitro studies showed faster growth of serotype 19A over 15B/C. Both were equally capable of colonization and middle ear infection in this model. Serotype 19A is included in new conjugate vaccine formulations while serotype 15B/C is not. Non-capsular vaccine targets will be important in disease prevention efforts.",,"['Laufer, Alison S.', 'Thomas, Jonathan C.', 'Figueira, Marisol', 'Gent, Janneane F.', 'Pelton, Stephen I.', 'Pettigrew, Melinda M.']",,,,
,PMC,Autophagy in Viral Replication and Pathogenesis,http://dx.doi.org/10.1007/s10059-010-0014-2,PMC3115743,,,"Autophagy is a catabolic process that is important for the removal of damaged organelles and long-lived proteins for the maintenance of cellular homeostasis. It can also serve as innate immunity to remove intracellular microbial pathogens. A growing list of viruses has been shown to affect this cellular pathway. Some viruses suppress this pathway for their survival, while others enhance or exploit this pathway to benefit their replication. The effect of viruses on autophagy may also sensitize cells to death or enhance cell survival and play a critical role in viral pathogenesis. In this article, we review the relationships between different viruses and autophagy and discuss how these relationships may affect viruses and their host cells.",,"['Sir, Donna', 'Ou, Jing-hsiung James']",,,,
,PMC,Optimized detection of sequence variation in heterozygous genomes using DNA microarrays with isothermal-melting probes,http://dx.doi.org/10.1073/pnas.0913883107,PMC2824413,,,"The use of DNA microarrays to identify nucleotide variation is almost 20 years old. A variety of improvements in probe design and experimental conditions have brought this technology to the point that single-nucleotide differences can be efficiently detected in unmixed samples, although developing reliable methods for detection of mixed sequences (e.g., heterozygotes) remains challenging. Surprisingly, a comprehensive study of the probe design parameters and experimental conditions that optimize discrimination of single-nucleotide polymorphisms (SNPs) has yet to be reported, so the limits of this technology remain uncertain. By targeting 24,549 SNPs that differ between two Saccharomyces cerevisiae strains, we studied the effect of SNPs on hybridization efficiency to DNA microarray probes of different lengths under different hybridization conditions. We found that the critical parameter for optimization of sequence discrimination is the relationship between probe melting temperature (T(m)) and the temperature at which the hybridization reaction is performed. This relationship can be exploited through the design of microarrays containing probes of equal T(m) by varying the length of probes. We demonstrate using such a microarray that we detect >90% homozygous SNPs and >80% heterozygous SNPs using the SNPScanner algorithm. The optimized design and experimental parameters determined in this study should guide DNA microarray designs for applications that require sequence discrimination such as mutation detection, genotyping of unmixed and mixed samples, and allele-specific gene expression. Moreover, designing microarray probes with optimized sensitivity to mismatches should increase the accuracy of standard microarray applications such as copy-number variation detection and gene expression analysis.",,"['Gresham, David', 'Curry, Bo', 'Ward, Alexandra', 'Gordon, D. Benjamin', 'Brizuela, Leonardo', 'Kruglyak, Leonid', 'Botstein, David']",,,,
,PMC,Association of Increased Prenatal Estrogen With Risk Factors for Schizophrenia,http://dx.doi.org/10.1093/schbul/sbp161,PMC3160212,,,"The author previously described a theoretical cause of schizophrenia based on the effects of estrogenic endocrine disruption. In the current review, the author describes how increased estrogen during pregnancy increases susceptibility to certain viral infections associated with increased risk for schizophrenia. The review further discusses how prenatal estrogen exposure could explain associations of schizophrenia with autoimmune diseases, urban environments, and stress. Based on the association of increased estrogen with schizophrenia risk factors, the author proposes increased prenatal estrogen as a unifying factor, perhaps the primary event, in the etiology of schizophrenia.",,"Brown, James S.",,,,
,PMC,Receptor-Based Discovery of a Plasmalemmal Monoamine Transporter Inhibitor via High-Throughput Docking and Pharmacophore Modeling,http://dx.doi.org/10.1021/cn900032u,PMC2843925,,,"[Image: see text] Recognition of psychostimulants such as cocaine and the amphetamines by the dopamine transporter (DAT) protein is principally responsible for the euphoria and addiction associated with these drugs. Using as a template the crystal structure of a distantly related bacterial leucine transporter, we have generated 3-D DAT computer molecular models. Ligand docking to such models has revealed potential substrate and inhibitor binding pockets, subsequently confirmed by in vitro pharmacology. An inhibitor pocket defined by the DAT model to be within the “extracellular vestibule”, just to the extracellular side of the external gate of the primary substrate pocket, was used for virtual screening of a structural library of compounds. High-throughput docking and application of pharmacophore constraints within this vestibular inhibitor pocket identified a compound structurally dissimilar to the classic monoamine (dopamine, norepinephrine, and serotonin) transporter (MAT) inhibitors. The compound displaced binding of radiolabeled cocaine analogs at all three MATs, usually with nanomolar K(i) values and within 2-fold of cocaine’s affinity at the norepinephrine transporter. Although a very weak dopamine uptake inhibitor itself, this compound reduced by 3-fold the potency of cocaine in inhibiting DAT-mediated cellular uptake of dopamine. To our knowledge, the present findings are the first to successfully employ “receptor-based” computer modeling to identify moderate- to high-affinity MAT ligands. In silico ligand screening using MAT models provides a rapid, low-cost discovery process that should accelerate identification of novel ligand scaffolds and provide lead compounds in combating psychostimulant addiction and in treating other monoamine-related CNS diseases.",,"['Indarte, Martín', 'Liu, Yi', 'Madura, Jeffry D.', 'Surratt, Christopher K.']",,,,
,PMC,Advances in the Renin Angiotensin System: Focus on Angiotensin-Converting Enzyme 2 and Angiotensin-(1–7),http://dx.doi.org/10.1016/S1054-3589(10)59007-0,PMC5863743,,,"The contribution of the renin angiotensin system to physiology and pathology is undergoing a rapid reconsideration of its mechanisms from emerging new concepts implicating angiotensin-converting enzyme 2 and angiotensin-(1–7) as new elements negatively influencing the vasoconstrictor, trophic, and pro-inflammatory actions of angiotensin II. This component of the system acts to oppose the vasoconstrictor and proliferative effects on angiotensin II through signaling mechanisms mediated by the mas receptor. In addition, a reduced expression of the vasodepressor axis composed by angiotensin-converting enzyme 2 and angiotensin-(1–7) may contribute to the expression of essential hypertension, the remodeling of heart and renal function associated with this disease, and even the physiology of pregnancy and the development of eclampsia.",,"['Ferrario, Carlos M.', 'Ahmad, Sarfaraz', 'Joyner, JaNae', 'Varagic, Jasmina']",,,,
,PMC,New immune pathways from chronic post-viral lung disease,http://dx.doi.org/10.1111/j.1749-6632.2009.05136.x,PMC3060024,,,"To better understand the immunopathogenesis of chronic inflammatory lung disease, we established a mouse model of disease that develops after respiratory viral infection. The disease that develops in this model is similar to chronic obstructive lung disease in humans. Using this model we have characterized two distinct phases in the chronic disease process. The first phase appears at three weeks after viral infection and depends on type I interferon-dependent expression and then subsequent activation of the high-affinity IgE receptor (FcεRI) on conventional lung dendritic cells, which in turn recruit IL-13-producing CD4(+) T cells to the lower airways. The second phase becomes maximal at seven weeks after infection and depends on invariant natural killer T (iNKT) cells and lung macrophages. Cellular cross-talk relies on interactions between the semi-invariant Vα14Jα18 T-cell receptor on lung iNKT cells and CD1d on macrophages as well as iNKT cell-derived IL-13 and IL-13 receptor on macrophages. These interactions drive macrophages to a pattern of alternative activation and overproduction of IL-13. This innate immune axis is also activated in patients with chronic obstructive lung disease, as evidenced by increased numbers of iNKT cells and IL-13-producing alternatively activated macrophages marked by chitinase 1 production. Together the findings identify two new immune pathways responsible for early and late phases of chronic inflammatory lung disease in experimental and clinical settings. These findings extend our understanding of the complex mechanisms that underlie chronic obstructive lung disease and provide useful targets for diagnosis and therapy of this common disorder.",,"['Benoit, Loralyn A.', 'Holtzman, Michael J.']",,,,
,PMC,Ecogenomics of Respiratory Diseases of Public Health Significance,http://dx.doi.org/10.1146/annurev.publhealth.012809.103633,PMC3402173,,,"Gene-environment interactions are the indisputable cause of most respiratory diseases. However, we still have very limited understanding of the mechanisms that guide these interactions. Although the conceptual approaches to environmental genomics were established several decades ago, the tools are only now available to better define the mechanisms that underlie the interactions among these important etiological features of lung disease. In this article, we summarize recent insights in the environmental genomics (ecogenomics) of common nonmalignant respiratory diseases (asthma, COPD, pulmonary fibrosis, and respiratory infections), describe the framework of gene-environment interactions that inform the pathogenesis of respiratory diseases, and propose future research directions that will help translate scientific advances into public health gains.",,"['Garantziotis, Stavros', 'Schwartz, David A.']",,,,
,PMC,A Unique BSL-3 Cryo-Electron Microscopy Laboratory at UTMB,,PMC3156611,,,"This article describes a unique cryo-electron microscopy (CryoEM) facility to study the three-dimensional organization of viruses at biological safety level 3 (BSL-3). This facility, the W. M. Keck Center for Virus Imaging, has successfully operated for more than a year without incident and was cleared for select agent studies by the Centers for Disease Control and Prevention (CDC). Standard operating procedures for the laboratory were developed and implemented to ensure its safe and efficient operation. This facility at the University of Texas Medical Branch (Galveston, TX) is the only such BSL-3 CryoEM facility approved for select agent research.",,"['Sherman, Michael B.', 'Freiberg, Alexander N.', 'Razmus, Dennis', 'Yazuka, Shintaro', 'Koht, Craig', 'Hilser, Vincent J.', 'Lemon, Stanley M.', 'Brocard, Anne-Sophie', 'Zimmerman, Dee', 'Chiu, Wah', 'Watowich, Stanley J.', 'Weaver, Scott C.']",,,,
,PMC,Receptor mimicry as novel therapeutic treatment for biothreat agents,http://dx.doi.org/10.4161/bbug.1.1.10049,PMC3035151,,,"The specter of intentional release of pathogenic microbes and their toxins is a real threat. This article reviews the literature on adhesins of biothreat agents, their interactions with oligosaccharides and the potential for anti-adhesion compounds as an alternative to conventional therapeutics. The minimal binding structure of ricin has been well characterised and offers the best candidate for successful anti-adhesion therapy based on the Galβ1-4GlcNAc structure. The botulinum toxin serotypes A–F bind to a low number of gangliosides (GT1b, GQ1b, GD1a and GD1b) hence it should be possible to determine the minimal structure for binding. The minimal disaccharide sequence of GalNAcβ1-4Gal found in the gangliosides asialo-GM1 and asialo-GM2 is required for adhesion for many respiratory pathogens. Although a number of adhesins have been identified in bacterial biothreat agents such as Yersinia pestis, Bacillus anthracis, Francisella tularensis, Brucella species and Burkholderia pseudomallei, specific information regarding their in vivo expression during pneumonic infection is lacking. Limited oligosaccharide inhibition studies indicate the potential of GalNAcβ1-4Gal, GalNAcβ-3Gal and the hydrophobic compound, para-nitrophenol as starting points for the rational design of generic anti-adhesion compounds. A cocktail of multivalent oligosaccharides based on the minimal binding structures of identified adhesins would offer the best candidates for anti-adhesion therapy.",,"Thomas, Richard J",,,,
,PMC,Quarantine: What is old is new,,PMC2809194,,,,,"Martell, David",,,,
,PMC,Identification and epidemiology of severe respiratory disease due to novel swine-origin influenza A (H1N1) virus infection in Alberta,,PMC3009582,,,"BACKGROUND: In March 2009, global surveillance started detecting cases of influenza-like illness in Mexico. By mid-April 2009, two pediatric patients were identified in the United States who were confirmed to be infected by a novel influenza A (H1N1) strain. The present article describes the first identified severe respiratory infection and the first death associated with pandemic H1N1 (pH1N1) in Canada. METHODS: Enhanced public health and laboratory surveillance for pH1N1 was implemented throughout Alberta on April 24, 2009. Respiratory specimens from all patients with a respiratory illness and travel history or those presenting with a severe respiratory infection requiring hospitalization underwent screening for respiratory viruses using molecular methods. For the first severe case identified and the first death due to pH1N1, histocompatibility leukocyte antigens were compared by molecular methods. RESULTS: The first death (a 39-year-old woman) occurred on April 28, 2009, and on May 1, 2009, a 10-year-old child presented with severe respiratory distress due to pH1N1. Both patients had no travel or contact with anyone who had travelled to Mexico; the cases were not linked. Histocompatibility antigen comparison of both patients did not identify any notable similarity. pH1N1 strains identified in Alberta did not differ from the Mexican strain. CONCLUSION: Rapid transmission of pH1N1 continued to occur in Alberta following the first death and the first severe respiratory infection in Canada, which were identified without any apparent connection to Mexico or the United States. Contact tracing follow-up suggested that oseltamivir may have prevented ongoing transmission of pH1N1.",,"['Zahariadis, George', 'Joffe, Ari R', 'Talbot, James', 'deVilliers, Albert', 'Campbell, Patricia', 'Pabbaraju, Kanti', 'Wong, Sallene', 'Bastien, Nathalie', 'Li, Yan', 'Mitchell, Robyn L', 'Pang, Xiao-Li', 'Yanow, Stephanie', 'Chui, Linda', 'Predy, Gerald', 'Willans, David', 'Lee, Bonita E', 'Preiksaitis, Jutta K', 'Clement, Bev', 'Jacobs, Angela', 'Jaipaul, Joy', 'Fonseca, Kevin']",,,,
,PMC,The accidental medical tourist,,PMC3009575,,,,,"['Laupland, Kevin B', 'Fisman, David N']",,,,
,PMC,"Respiratory Viral Infections in Infants: Causes, Clinical Symptoms, Virology, and Immunology",http://dx.doi.org/10.1128/CMR.00032-09,PMC2806659,,,"Summary: In global terms, respiratory viral infection is a major cause of morbidity and mortality. Infancy, in particular, is a time of increased disease susceptibility and severity. Early-life viral infection causes acute illness and can be associated with the development of wheezing and asthma in later life. The most commonly detected viruses are respiratory syncytial virus (RSV), rhinovirus (RV), and influenza virus. In this review we explore the complete picture from epidemiology and virology to clinical impact and immunology. Three striking aspects emerge. The first is the degree of similarity: although the infecting viruses are all different, the clinical outcome, viral evasion strategies, immune response, and long-term sequelae share many common features. The second is the interplay between the infant immune system and viral infection: the immaturity of the infant immune system alters the outcome of viral infection, but at the same time, viral infection shapes the development of the infant immune system and its future responses. Finally, both the virus and the immune response contribute to damage to the lungs and subsequent disease, and therefore, any prevention or treatment needs to address both of these factors.",,"['Tregoning, John S.', 'Schwarze, Jürgen']",,,,
,PMC,The pathogenesis of murine coronavirus infection of the central nervous system,,PMC2852265,,,"Mouse hepatitis virus (MHV) is a positive strand RNA virus that causes an acute encephalomyelitis which later resolves into a chronic fulminating demyelinating disease. Cytokine production, chemokine secretion, and immune cell infiltration into the central nervous system are critical to control viral replication during acute infection. Despite potent anti – viral T lymphocyte activity, sterile immunity is not achieved, and MHV chronically persists within oligodendrocytes. Continued infiltration and activation of the immune system, a result of the lingering viral antigen and RNA within oligodendrocytes, lead directly to the development of an immune – mediated demyelination that bears remarkable similarities, both clinically and histologically, to the human demyelinating disease multiple sclerosis. MHV offers a unique model system for studying host defense during acute viral infection and immune – mediated demyelination during chronic infection.",,"['Hosking, Martin P.', 'Lane, Thomas E.']",,,,
,PMC,Nucleotide Analogues as Probes for DNA and RNA Polymerases,http://dx.doi.org/10.1002/9780470559277.ch090203,PMC3149870,,,"Nucleotide analogues represent a major class of anti-cancer and anti-viral drugs, and provide an extremely powerful tool for dissecting the mechanisms of DNA and RNA polymerases. While the basic assays themselves are relatively straight-forward, a key issue is to appropriately design the studies to answer the mechanistic question of interest. This article addresses the major issues involved in designing these studies, and some of the potential difficulties that arise in interpreting the data. Examples are given both of the type of analogues typically used, the experimental approaches with different polymerases, and issues with data interpretation.",,"Kuchta, Robert D.",,,,
,PMC,VZV Infection of Keratinocytes: Production of Cell-Free Infectious Virions In Vivo,http://dx.doi.org/10.1007/82_2010_13,PMC5408736,,,"Varicella-zoster virus (VZV) is the cause of varicella (chickenpox) and zoster (shingles). Varicella is a primary infection that spreads rapidly in epidemics while zoster is a secondary infection that occurs sporadically as a result of the reactivation of previously acquired VZV. Reactivation is made possible by the establishment of latency during the initial episode of varicella. The signature lesions of both varicella and zoster are cutaneous vesicles, which are filled with a clear fluid that is rich in infectious viral particles. It has been postulated that the skin is the critical organ in which both host-to-host transmission of VZV and the infection of neurons to establish latency occur. This hypothesis is built on evidence that the large cation-independent mannose 6-phosphate receptor (MPR(ci)) interacts with VZV in virtually all infected cells, except those of the suprabasal epidermis, in a way that prevents the release of infectious viral particles. Specifically, the virus is diverted in an MPR(ci)-dependent manner from the secretory pathway to late endosomes where VZV is degraded. Because nonepidermal cells are thus prevented from releasing infectious VZV, a slow process, possibly involving fusion of infected cells with their neighbors, becomes the means by which VZV is disseminated. In the epidermis, however, the maturation of keratinocytes to give rise to corneocytes in the suprabasal epidermis is associated uniquely with a downregulation of the MPR(ci). As a result, the diversion of VZV to late endosomes does not occur in the suprabasal epidermis where vesicular lesions occur. The formation of the waterproof, chemically resistant barrier of the epidermis, however, requires that constitutive secretion outlast the downregulation of the endosomal pathway. Infectious VZV is therefore secreted by default, accounting for the presence of infectious virions in vesicular fluid. Sloughing of corneocytes, aided by scratching, then aerosolizes the virus, which can float with dust to be inhaled by susceptible hosts. Infectious virions also bathe the terminals of those sensory neurons that innervate the epidermis. These terminals become infected with VZV and provide a route, retrograde transport, which can conduct VZV to cranial nerve (CNG), dorsal root ganglia (DRG), and enteric ganglia (EG) to establish latency. Reactivation returns VZV to the skin, now via anterograde transport in axons, to cause the lesions of zoster. Evidence in support of these hypotheses includes observations of the VZV-infected human epidermis and studies of guinea pig neurons in an in vitro model system.",,"['Gershon, Michael D.', 'Gershon, Anne A.']",,,,
,PMC,From Touchdown to Transcription: The Reovirus Cell Entry Pathway,http://dx.doi.org/10.1007/82_2010_32,PMC4714703,,,"Mammalian orthoreoviruses (reoviruses) are prototype members of the Reoviridae family of nonenveloped viruses. Reoviruses contain ten double-stranded RNA gene segments enclosed in two concentric protein shells, outer capsid and core. These viruses serve as a versatile experimental system for studies of virus cell entry, innate immunity, and organ-specific disease. Reoviruses engage cells by binding to cell-surface carbohydrates and the immunoglobulin superfamily member, junctional adhesion molecule-A (JAM-A). JAM-A is a homodimer formed by extensive contacts between its N-terminal immunoglobulin-like domains. Reo-virus attachment protein σ1 disrupts the JAM-A dimer, engaging a single JAM-A molecule by virtually the same interface used for JAM-A homodimerization. Following attachment to JAM-A and carbohydrate, reovirus internalization is promoted by β1 integrins, most likely via clathrin-dependent endocytosis. In the endocytic compartment, reovirus outer-capsid protein σ3 is removed by cathepsin proteases, which exposes the viral membrane-penetration protein, μ1. Proteolytic processing and conformational rearrangements of μ1 mediate endosomal membrane rupture and delivery of transcriptionally active reovirus core particles into the host cell cytoplasm. These events also allow the ϕ cleavage fragment of μ1 to escape into the cytoplasm where it activates NF-κB and elicits apoptosis. This review will focus on mechanisms of reovirus cell entry and activation of innate immune response signaling pathways.",,"['Danthi, Pranav', 'Guglielmi, Kristen M.', 'Kirchner, Eva', 'Mainou, Bernardo', 'Stehle, Thilo', 'Dermody, Terence S.']",,,,
,PMC,Internalization and fusion mechanism of vesicular stomatitis virus and related rhabdoviruses,http://dx.doi.org/10.2217/FVL.09.72,PMC3600636,,,"Members of the Rhabdoviridae infect a wide variety of animals and plants, and are the causative agents of many important diseases. Rhabdoviruses enter host cells following internalization into endosomes, with the glycoprotein (G protein) mediating both receptor binding to host cells and fusion with the cellular membrane. The recently solved crystal structure of vesicular stomatitis virus G has allowed considerable insight into the mechanism of rhabdovirus entry, in particular the low pH-dependent conformational changes that lead to fusion activation. Rhabdovirus entry shows several distinct features compared with other enveloped viruses; first, the entry process appears to consist of two distinct fusion events, initial fusion into vesicles within endosomes followed by back-fusion into the cytosol; second, the conformational changes in the G protein that lead to fusion activation are reversible; and third, the G protein is structurally distinct from other viral fusion proteins and is not proteolytically cleaved. The internalization and fusion mechanisms of rhabdoviruses are discussed in this article, with a focus on viral systems where the G protein has been studied extensively: vesicular stomatitis virus and rabies virus, as well as viral hemorrhagic septicemia virus.",,"['Sun, Xiangjie', 'Roth, Shoshannah L', 'Bialecki, Michele A', 'Whittaker, Gary R']",,,,
,PMC,Genome-wide mapping of SMAD target genes reveals the role of BMP signaling in embryonic stem cell fate determination,http://dx.doi.org/10.1101/gr.092114.109,PMC2798829,,,"Embryonic stem (ES) cells are under precise control of both intrinsic self-renewal gene regulatory network and extrinsic growth factor-triggered signaling cascades. How external signaling pathways connect to core self-renewal transcriptional circuits is largely unknown. To probe this, we chose BMP signaling, which is previously recognized as a master control for both self-renewal and lineage commitment of murine ES cells. Here, we mapped target gene promoter occupancy of SMAD1/5 and SMAD4 on a genome-wide scale and found that they associate with a large group of developmental regulators that are enriched for H3K27 trimethylation and H3K4 trimethylation bivalent marks and are repressed in the self-renewing state, whereas they are rapidly induced upon differentiation. Smad knockdown experiments further indicate that SMAD-mediated BMP signaling is largely required for differentiation-related processes rather than directly influencing self-renewal. Among the SMAD-associated genes, we further identified Dpysl2 (previously known as Crmp2) and the H3K27 demethylase Kdm6b (previously known as Jmjd3) as BMP4-modulated early neural differentiation regulators. Combined with computational analysis, our results suggest that SMAD-mediated BMP signaling balances self-renewal versus differentiation by modulating a set of developmental regulators.",,"['Fei, Teng', 'Xia, Kai', 'Li, Zhongwei', 'Zhou, Bing', 'Zhu, Shanshan', 'Chen, Hua', 'Zhang, Jianping', 'Chen, Zhang', 'Xiao, Huasheng', 'Han, Jing-Dong J.', 'Chen, Ye-Guang']",,,,
,PMC,Microbe Hunting in Laboratory Animal Research,,PMC4107416,,,"Recent advances in nucleic acid diagnostic technologies have revolutionized microbiology by facilitating rapid, sensitive pathogen surveillance and differential diagnosis of infectious diseases. With the expansion and dissemination of genomic sequencing technology scientists are discovering new microbes at an accelerating pace. In this article we review recent progress in the field of pathogen surveillance and discovery with a specific focus on applications in the field of laboratory animal research. We discuss the challenges in proving a causal relationship between the presence of a candidate organism and disease. We also discuss the strengths and limitations of various assay platforms and describe a staged strategy for viral diagnostics. To illustrate the complexity of pursuing pathogen discovery research, we include examples from our own work that are intended to provide insights into the process that led to the selection of particular strategies.",,"['Palacios, Gustavo', 'Briese, Thomas', 'Lipkin, W. Ian']",,,,
,PMC,Generation and characterization of chicken bone marrow-derived dendritic cells,http://dx.doi.org/10.1111/j.1365-2567.2009.03129.x,PMC2807494,,,"Dendritic cells (DCs) are bone marrow-derived professional antigen-presenting cells. The in vitro generation of DCs from either bone marrow or blood is routine in mammals. Their distinct morphology and phenotype and their unique ability to stimulate naïve T cells are used to define DCs. In this study, chicken bone marrow cells were cultured in the presence of recombinant chicken granulocyte–macrophage colony-stimulating factor (GM-CSF) and recombinant chicken interleukin-4 (IL-4) for 7 days. The cultured population showed the typical morphology of DCs, with the surface phenotype of major histocompatibility complex (MHC) class II(+) (high), CD11c(+) (high), CD40(+) (moderate), CD1·1(+) (moderate), CD86(+) (low), CD83(−) and DEC-205(−). Upon maturation with lipopolysaccharide (LPS) or CD40L, surface expression of CD40, CD1·1, CD86, CD83 and DEC-205 was greatly increased. Endocytosis and phagocytosis were assessed by fluorescein isothiocyanate (FITC)-dextran uptake and fluorescent bead uptake, respectively, and both decreased after stimulation. Non-stimulated chicken bone marrow-derived DCs (chBM-DCs) stimulated both allogeneic and syngeneic peripheral blood lymphocytes (PBLs) to proliferate in a mixed lymphocyte reaction (MLR). LPS- or CD40L-stimulated chBM-DCs were more effective T-cell stimulators in MLR than non-stimulated chBM-DCs. Cultured chBM-DCs could be matured to a T helper type 1 (Th1)-promoting phenotype by LPS or CD40L stimulation, as determined by mRNA expression levels of Th1 and Th2 cytokines. We have therefore cultured functional chBM-DCs in a non-mammalian species for the first time.",,"['Wu, Zhiguang', 'Rothwell, Lisa', 'Young, John R', 'Kaufman, Jim', 'Butter, Colin', 'Kaiser, Pete']",,,,
,PMC,Development of an electronic public health case report using HL7 v2.5 to meet public health needs,http://dx.doi.org/10.1197/jamia.M3299,PMC2995632,,,"Clinicians are required to report selected conditions to public health authorities within a stipulated amount of time. The current reporting process is mostly paper-based and inefficient and may lead to delays in case investigation. As electronic medical records become more prevalent, electronic case reporting is becoming increasingly feasible. However, there is no existing standard for the electronic transmission of case reports from healthcare to public health entities. We identified the major requirements of electronic case reports and verified that the requirements support the work processes of the local health departments. We propose an extendable standards-based model to electronically transmit case information and associated laboratory information from healthcare to public health entities. The HL7 v2.5 message model is currently being implemented to transmit electronic case reports from Intermountain Healthcare to the Utah Department of Health.",,"['Rajeev, Deepthi', 'Staes, Catherine J', 'Evans, R Scott', 'Mottice, Susan', 'Rolfs, Robert', 'Samore, Matthew H', 'Whitney, Jon', 'Kurzban, Richard', 'Huff, Stanley M']",,,,
,PMC,Overcoming the Solubility Limit with Solubility-Enhancement Tags: Successful Applications in Biomolecular NMR Studies,http://dx.doi.org/10.1007/s10858-009-9371-6,PMC2879018,,,"Although the rapid progress of NMR technology has significantly expanded the range of NMR-trackable systems, preparation of NMR-suitable samples that are highly soluble and stable remains a bottleneck for studies of many biological systems. The application of solubility-enhancement tags (SETs) has been highly effective in overcoming solubility and sample stability issues and has enabled structural studies of important biological systems previously deemed unapproachable by solution NMR techniques. In this review, we provide a brief survey of the development and successful applications of the SET strategy in biomolecular NMR. We also comment on the criteria for choosing optimal SETs, such as for differently charged target proteins, and recent new developments on NMR-invisible SETs.",,"['Zhou, Pei', 'Wagner, Gerhard']",,,,
,PMC,"Development of a Rapid Automated Influenza A, Influenza B, and Respiratory Syncytial Virus A/B Multiplex Real-Time RT-PCR Assay and Its Use during the 2009 H1N1 Swine-Origin Influenza Virus Epidemic in Milwaukee, Wisconsin",http://dx.doi.org/10.2353/jmoldx.2010.090095,PMC2797721,,,"Rapid, semiautomated, and fully automated multiplex real-time RT-PCR assays were developed and validated for the detection of influenza (Flu) A, Flu B, and respiratory syncytial virus (RSV) from nasopharyngeal specimens. The assays can detect human H1N1, H3N2, and swine-origin (S-OIV) H1N1 Flu A viruses and were effectively used to distinguish Flu A infections (of all subtypes) from Flu B and RSV infections during the current S-OIV outbreak in Milwaukee, WI. The analytical limits of detection were 10(−2) to 10(1) TCID(50)/ml depending on the platform and analyte and showed only one minor cross-reaction among 23 common respiratory pathogens (intermittent cross-reaction to adenovirus at >10(7) TCID(50)/ml). A total of 100 clinical samples were tested by tissue culture, both automated assays, and the US Food and Drug Administration-approved ProFlu+ assay. Both the semiautomated and fully automated assays exhibited greater overall (Flu A, Flu B, and RSV combined) clinical sensitivities (93 and 96%, respectively) and individual Flu A sensitivities (100%) than the Food and Drug Administration-approved test (89% overall sensitivity and 93% Flu A sensitivity). All assays were 99% specific. During the S-OIV outbreak in Milwaukee, WI, the fully automated assay was used to test 1232 samples in 2 weeks. Flu A was detected in 134 clinical samples (126 H1N1 S-OIV, 5 H1N1 [human], and 1 untyped) with 100% positive agreement compared with other “in-house” validated molecular assays, with only 2 false-positive results. Such accurate testing using automated high-throughput molecule systems should allow clinicians and public health officials to react quickly and effectively during viral outbreaks.",,"['Beck, Eric T.', 'Jurgens, Lisa A.', 'Kehl, Sue C.', 'Bose, Michael E.', 'Patitucci, Teresa', 'LaGue, Elizabeth', 'Darga, Patrick', 'Wilkinson, Kimberly', 'Witt, Lorraine M.', 'Fan, Jiang', 'He, Jie', 'Kumar, Swati', 'Henrickson, Kelly J.']",,,,
,PMC,"Neutralizing epitopes of the SARS-CoV S-protein cluster independent of repertoire, antigen structure or mAb technology",,PMC2828578,,,"Neutralizing antibody responses to the surface glycoproteins of enveloped viruses play an important role in immunity. Many of these glycoproteins, including the severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) protein form trimeric units in the membrane of the native virion. There is substantial experimental and pre-clinical evidence showing that the S protein is a promising lead for vaccines and therapeutics. Previously we generated a panel of monoclonal antibodies (mAbs) to whole inactivated SARS-CoV which neutralize the virus in vitro.1,2 Here, we define their specificity and affinity, map several of their epitopes and lastly characterise chimeric versions of them. Our data show that the neutralizing mAbs bind to the angiotensin-converting enzyme 2 (ACE2) receptor-binding domain (RBD) of the SARS S protein. Three of the chimeric mAbs retain their binding specificity while one conformational mAb, F26G19, lost its ability to bind the S protein despite high level expression. The affinity for recombinant S is maintained in all of the functional chimeric versions of the parental mAbs. Both parental mAb F26G18 and the chimeric version neutralize the TOR2 strain of SARS-CoV with essentially identical titres (2.07 and 2.47 nM, respectively). Lastly, a comparison with other neutralizing mAbs to SARS-CoV clearly shows that the dominance of a 33 amino acid residue loop of the SARS-CoV RBD is independent of repertoire, species, quaternary structure, and importantly, the technology used to derive the mAbs. In cases like this, the dominance of a compact RBD antigenic domain and the central role of the S protein in pathogenesis may inherently create immunoselection pressure on viruses to evolve more complex evasion strategies or die out of a host species. The apparent simplicity of the mechanism of SARS-CoV neutralization is in stark contrast to the complexity shown by other enveloped viruses.",,"['Berry, Jody D', 'Hay, Kevin', 'Rini, James M', 'Yu, Meng', 'Wang, Linfa', 'Plummer, Francis A', 'Corbett, Cindi R', 'Andonov, Anton']",,,,
,PMC,Zinc: a new risk factor for pneumonia in the elderly?,http://dx.doi.org/10.1111/j.1753-4887.2009.00253.x,PMC2854541,,,"Zinc may be a new risk factor for pneumonia in the elderly. In this special article, we reviewed the magnitude of the problem of pneumonia (its prevalence, morbidity and mortality) in the elderly, its etiology, and the dysregulation of the immune system associated with increasing age. In addition, we presented evidence from the literature, including work we did recently, that low zinc status (commonly reported in the elderly) impairs immune function, decreases resistance to pathogens, and is associated not only with increased incidence and duration of pneumonia, increased use and duration of antimicrobial treatment, but also with increased overall mortality in the elderly. Inadequate stores of zinc might therefore be a risk factor for pneumonia in the elderly. Randomized, double blind, controlled studies are needed to determine the efficacy of zinc supplementation as a potential low cost intervention to reduce morbidity and mortality due to pneumonia in this vulnerable population.",,"['Barnett, Junaidah B.', 'Hamer, Davidson H.', 'Meydani, Simin N.']",,,,
,PMC,1918 and 2009: A Tale of Two Pandemics,,PMC2862328,,,,,"['Redd, Stephen C.', 'Frieden, Thomas R.', 'Schuchat, Anne', 'Briss, Peter A.']",,,,
,PMC,Public Health Laboratory System Improvement Program: Development and Implementation,,PMC2846800,,,"Instruments designed to measure the performance of public health systems at state and local levels were supported by the Centers for Disease Control and Prevention (CDC) and implemented in 2002. This article describes the process and outcomes of a system and tool designed to measure performance of State Public Health Laboratory Systems, accomplished by the Association of Public Health Laboratories (APHL) in partnership with CDC. We describe the process used to develop the instrument and its subsequent pilot testing and field testing in 11 states. Throughout the field testing and early implementation phases, both CDC and APHL recognized that the core rationale for measuring system performance would be to provide the basis for subsequent system improvement. APHL implemented the Laboratory System Improvement Program (L-SIP) in 2007 and conducted an evaluation of the field testing of the instrument and related materials that same year. We conclude with a summary of future implications for L-SIP, the prograM&Apos;s recognition as an international standard for laboratory systems, and the critical importance of its continuation.",,"['Milne, Kathleen C.', 'Milne, Thomas L.']",,,,
,PMC,The History of Ultraviolet Germicidal Irradiation for Air Disinfection,,PMC2789813,,,"Public health concerns such as multi- and extensive drug-resistant tuberculosis, bioterrorism, pandemic influenza, and severe acute respiratory syndrome have intensified efforts to prevent transmission of infections that are completely or partially airborne using environmental controls. One such control, ultraviolet germicidal irradiation (UVGI), has received renewed interest after decades of underutilization and neglect. With renewed interest, however, come renewed questions, especially regarding efficacy and safety. There is a long history of investigations concluding that, if used properly, UVGI can be safe and highly effective in disinfecting the air, thereby preventing transmission of a variety of airborne infections. Despite this long history, many infection control professionals are not familiar with the history of UVGI and how it has, and has not, been used safely and effectively. This article reviews that history of UVGI for air disinfection, starting with its biological basis, moving to its application in the real world, and ending with its current status.",,"Reed, Nicholas G.",,,,
,PMC,"Traditions, Transitions, and Transfats: New Directions for Public Health",,PMC2789811,,,,,"['Rosner, David', 'Fried, Linda P.']",,,,
,PMC,Potential Triggers of MS,http://dx.doi.org/10.1007/400_2008_12,PMC3048788,,,"MS is an immune mediated disease of the central nervous system (CNS) characterized by demyelination, axonal damage and neurologic disability. The primary cause of this CNS disease remains elusive. Here we will address our current understanding of the role of viruses as potential environmental triggers for MS. Virus infections can act peripherally (outside the CNS) or within the CNS. The association of viral infections with demyelinating disease, in both animals and humans, will be discussed, as will the potential contributions of peripheral infection with Torque Teno virus, infection outside of and/or within the CNS with Epstein-Barr virus and infection within the CNS with Human Herpesvirus 6 to MS. An experimental animal model, Theiler’s murine encephalomyelitis virus infection of susceptible strains of mice is an example of viral infections of the CNS as a prerequisite for demyelination. Finally, the proposition that multiple virus infections, which first prime the immune system and then trigger the disease, as a model where infections outside of the CNS lead to inflammatory changes within the CNS, are required for the development of a MS-like disease is explored.",,"['Libbey, Jane E.', 'Fujinami, Robert S.']",,,,
,PMC,Calciomics: prediction and analysis of EF-hand calcium binding proteins by protein engineering,,PMC2926812,,,"Ca(2+) plays a pivotal role in the physiology and biochemistry of prokaryotic and mammalian organisms. Viruses also utilize the universal Ca(2+) signal to create a specific cellular environment to achieve coexistence with the host, and to propagate. In this paper we first describe our development of a grafting approach to understand site-specific Ca(2+) binding properties of EF-hand proteins with a helix-loop-helix Ca(2+) binding motif, then summarize our prediction and identification of EF-hand Ca(2+) binding sites on a genome-wide scale in bacteria and virus, and next report the application of the grafting approach to probe the metal binding capability of predicted EF-hand motifs within the streptococcal hemoprotein receptor (Shr) of Streptococcus pyrogenes and the nonstructural protein 1 (nsP1) of Sindbis virus. When methods such as the grafting approach are developed in conjunction with prediction algorithms we are better able to probe continuous Ca(2+)-binding sites that have been previously underrepresented due to the limitation of conventional methodology.",,"['YanYi, CHEN', 'ShengHui, XUE', 'YuBin, ZHOU', 'Jie, YANG Jenny']",,,,
,PMC,IDENTIFICATION AND VALIDATION OF ISG15 TARGET PROTEINS,http://dx.doi.org/10.1007/978-1-4419-6676-6_18,PMC5912676,,,"ISG15 is an interferon-induced ubiquitin-like protein (Ubl) that has antiviral properties. The core El, E2 and E3 enzymes for conjugation of human ISG15 are Ube1L, UbcH8 and Herc5, all of which are induced at the transcriptional level by Type 1 interferon signaling. Several proteomics studies have, together, identified over 300 cellular proteins as ISG15 targets. These targets include a broad range of constitutively expressed proteins and approximately 15 interferon-induced proteins. This chapter provides an overview of the target identification process and the validation of these targets. We also discuss the limited number of examples where the biochemical effect of ISG15 conjugation on target proteins has been characterized.",,"['Durfee, Larissa A.', 'Huibregtse, Jon M.']",,,,
,PMC,Gamma Interferon Signaling in Oligodendrocytes Is Critical for Protection from Neurotropic Coronavirus Infection,http://dx.doi.org/10.1128/JVI.02373-09,PMC2826048,,,"Neurotropic coronavirus induces acute encephalomyelitis and demyelination in mice. Infection of BALB/c (H-2(d)) mice expressing a dominant negative gamma interferon (IFN-γ) receptor specifically in oligodendrocytes was examined to determine the influence of IFN-γ signaling on pathogenesis. Inhibition of IFN-γ signaling in oligodendrocytes increased viral load, infection of oligodendrocytes, oligodendrocyte loss, demyelination, and axonal damage resulting in increased mortality. IFN-γ levels and the inflammatory response were not altered, although the level of tumor necrosis factor (TNF) mRNA was increased. These data indicate that IFN-γ signaling by oligodendroglia reduces viral replication but affects both demyelination and tissue destruction in a host-specific manner.",,"['Parra, Gabriel I.', 'Bergmann, Cornelia C.', 'Phares, Timothy W.', 'Hinton, David R.', 'Atkinson, Roscoe', 'Stohlman, Stephen A.']",,,,
,PMC,Recent Advances in the Study of Human Antibody Responses to Influenza Virus Using Optimized Human Hybridoma Approaches,http://dx.doi.org/10.1016/j.vaccine.2009.10.124,PMC2835990,,,Influenza viruses exhibit a fascinating level of antigenic heterogeneity that facilitates re-infection in the human population. The human antibody repertoire also manifests endless capability for variation in the genes that specify the portion of antibody molecules interacting with epitopes. A recent explosion of techniques for isolating human monoclonal antibodies to viruses has led to isolation of new antibodies that allow glimpses into the molecular basis for recognition and escape that underlies the constant antigenic drift in influenza surface proteins. These studies also reveal evidence for lifelong persistence of immunity to some influenza viruses.,,"Crowe, James E.",,,,
,PMC,Monoclonal antibody-based therapies for microbial diseases,http://dx.doi.org/10.1016/j.vaccine.2009.09.105,PMC2810317,,,"The monoclonal antibody (mAb) revolution that currently provides many new options for the treatment of neoplastic and inflammatory diseases has largely bypassed the field of infectious diseases. Only one mAb is licensed for use against an infectious disease, although there are many in various stages of development. This situation is peculiar given that serum therapy was one of the first effective treatments for microbial diseases and that specific antibodies have numerous antimicrobial properties. The underdevelopment and underutilization of mAb therapies for microbial diseases has various complex explanations that include the current availability of antimicrobial drugs, small markets, high costs and microbial antigenic variation. However, there are signs that the climate for mAb therapeutics in infectious diseases is changing given increasing antibiotic drug resistance, the emergence of new pathogenic microbes for which no therapy is available, and development of mAb cocktail formulations. Currently, the major hurdle for the widespread introduction of mAb therapies for microbial diseases is economic, given the high costs of immunoglobulin preparations and relatively small markets. Despite these obstacles there are numerous opportunities for mAb development against microbial diseases and the development of radioimmunotherapy provides new options for enhancing the magic bullet. Hence, there is cautious optimism that the years ahead will see more mAbs in clinical use against microbial diseases.",,"['Saylor, Carolyn', 'Dadachova, Ekaterina', 'Casadevall, Arturo']",,,,
,PMC,Binding of a potent small-molecule inhibitor of six-helix bundle formation requires interactions with both heptad-repeats of the RSV fusion protein,http://dx.doi.org/10.1073/pnas.0910108106,PMC2806771,,,"Six-helix bundle (6HB) formation is an essential step for many viruses that rely on a class I fusion protein to enter a target cell and initiate replication. Because the binding modes of small molecule inhibitors of 6HB formation are largely unknown, precisely how they disrupt 6HB formation remains unclear, and structure-based design of improved inhibitors is thus seriously hampered. Here we present the high resolution crystal structure of TMC353121, a potent inhibitor of respiratory syncytial virus (RSV), bound at a hydrophobic pocket of the 6HB formed by amino acid residues from both HR1 and HR2 heptad-repeats. Binding of TMC353121 stabilizes the interaction of HR1 and HR2 in an alternate conformation of the 6HB, in which direct binding interactions are formed between TMC353121 and both HR1 and HR2. Rather than completely preventing 6HB formation, our data indicate that TMC353121 inhibits fusion by causing a local disturbance of the natural 6HB conformation.",,"['Roymans, Dirk', 'De Bondt, Hendrik L.', 'Arnoult, Eric', 'Geluykens, Peggy', 'Gevers, Tom', 'Van Ginderen, Marcia', 'Verheyen, Nick', 'Kim, Hidong', 'Willebrords, Rudy', 'Bonfanti, Jean-François', 'Bruinzeel, Wouter', 'Cummings, Maxwell D.', 'van Vlijmen, Herman', 'Andries, Koen']",,,,
,PMC,Unbiased probing of the entire hepatitis C virus life cycle identifies clinical compounds that target multiple aspects of the infection,http://dx.doi.org/10.1073/pnas.0912966107,PMC2806752,,,"Over 170 million people are chronically infected by the hepatitis C virus (HCV) and at risk for dying from liver cirrhosis and hepatocellular carcinoma. Current therapy is expensive, associated with significant side effects, and often ineffective. Discovery of antiviral compounds against HCV traditionally involves a priori target identification followed by biochemical screening and confirmation in cell-based replicon assays. Typically, this results in the discovery of compounds that address a few predetermined targets and are prone to select for escape variants. To attempt to identify antiviral compounds with broad target specificity, we developed an unbiased cell-based screening system involving multiple rounds of infection in a 96-well format. Analysis of a publicly available library of 446 clinically approved drugs identified 33 compounds that targeted both known and previously unexplored aspects of HCV infection, including entry, replication, and assembly. Discovery of novel viral and cellular targets in this manner will broaden the therapeutic armamentarium against this virus, allowing for the development of drug mixtures that should reduce the likelihood of mutational escape.",,"['Gastaminza, Pablo', 'Whitten-Bauer, Christina', 'Chisari, Francis V.']",,,,
,PMC,An Improved Reverse Genetics System for Mammalian Orthoreoviruses,http://dx.doi.org/10.1016/j.virol.2009.11.037,PMC2823833,,,"Mammalian orthoreoviruses (reoviruses) are highly useful models for studies of double-stranded RNA virus replication and pathogenesis. We previously developed a strategy to recover prototype reovirus strain T3D from cloned cDNAs transfected into murine L929 fibroblast cells. Here, we report the development of a second-generation reovirus reverse genetics system featuring several major improvements: (1) the capacity to rescue prototype reovirus strain T1L, (2) reduction of required plasmids from ten to four, and (3) isolation of recombinant viruses following transfection of baby hamster kidney cells engineered to express bacteriophage T7 RNA polymerase. The efficiency of virus rescue using the 4-plasmid strategy was substantially increased in comparison to the original 10-plasmid system. We observed full compatibility of T1L and T3D rescue vectors when intermixed to produce a panel of T1L × T3D monoreassortant viruses. Improvements to the reovirus reverse genetics system enhance its applicability for studies of reovirus biology and clinical use.",,"['Kobayashi, Takeshi', 'Ooms, Laura S.', 'Ikizler, Mine', 'Chappell, James D.', 'Dermody, Terence S.']",,,,
,PMC,Backbone Model of an Aquareovirus Virion by Cryo-Electron Microscopy and Bioinformatics,http://dx.doi.org/10.1016/j.jmb.2009.12.027,PMC2900198,,,"Grass carp reovirus (GCRV) is a member of the aquareovirus genus in the Reoviridae family and has a capsid with two shells—a transcription-competent core surrounded by a coat. We report a near-atomic-resolution reconstruction of the GCRV virion by cryo-electron microscopy and single-particle reconstruction. A backbone model of the GCRV virion, including seven conformers of the five capsid proteins making up the 1500 molecules in both the core and the coat, was derived using cryo-electron microscopy density-map-constrained homology modeling and refinement. Our structure clearly showed that the amino-terminal segment of core protein VP3B forms an ~120-Å-long α-helix-rich extension bridging across the icosahedral 2-fold-symmetry-related molecular interface. The presence of this unique structure across this interface and the lack of an external cementing molecule at this location in GCRV suggest a stabilizing role of this extended amino-terminal density. Moreover, part of this amino-terminal extension becomes invisible in the reconstruction of transcription-competent core particles, suggesting its involvement in endogenous viral RNA transcription. Our structure of the VP1 turret represents its open state, and comparison with its related structures at the closed state suggests hinge-like domain movements associated with the mRNA-capping machinery. Overall, this first backbone model of an aquareovirus virion provides a wealth of structural information for understanding the structural basis of GCRV assembly and transcription.",,"['Cheng, Lingpeng', 'Zhu, Jiang', 'Hui, Wong Hoi', 'Zhang, Xiaokang', 'Honig, Barry', 'Fang, Qin', 'Zhou, Z. Hong']",,,,
,PMC,Optimizing infectious disease interventions during an emerging epidemic,http://dx.doi.org/10.1073/pnas.0908491107,PMC2818907,,,"The emergence and global impact of the novel influenza A(H1N1)v highlights the continuous threat to public health posed by a steady stream of new and unexpected infectious disease outbreaks in animals and humans. Once an emerging epidemic is detected, public health authorities will attempt to mitigate the epidemic by, among other measures, reducing further spread as much as possible. Scarce and/or costly control measures such as vaccines, anti-infective drugs, and social distancing must be allocated while epidemiological characteristics of the disease remain uncertain. Here we present first principles for allocating scarce resources with limited data. We show that under a broad class of assumptions, the simple rule of targeting intervention measures at the group with the highest risk of infection per individual will achieve the largest reduction in the transmission potential of a novel infection. For vaccination of susceptible persons, the appropriate risk measure is force of infection; for social distancing, the appropriate risk measure is incidence of infection. Unlike existing methods that rely on detailed knowledge of group-specific transmission rates, the method described here can be implemented using only data that are readily available during an epidemic, and allows ready adaptation as the epidemic progresses. The need to observe risk of infection helps to focus the ongoing planning and design of new infectious disease surveillance programs; from the presented first principles for allocating scarce resources, we can adjust the prioritization of groups for intervention when new observations on an emerging epidemic become available.",,"['Wallinga, Jacco', 'van Boven, Michiel', 'Lipsitch, Marc']",,,,
,PMC,Cognitive Recovery in the Aged Rat after Stroke and Anti-Nogo-A Immunotherapy,http://dx.doi.org/10.1016/j.bbr.2009.12.015,PMC2831114,,,"We have previously shown that immunotherapy directed against the protein Nogo-A leads to recovery on a skilled forelimb reaching task in rats after sensorimotor cortex stroke, which correlated with axonal and dendritic plasticity. Here we investigated anti-Nogo-A immunotherapy as an intervention to improve performance on a spatial memory task in aged rats after stroke, and whether cognitive recovery was correlated with structural plasticity. Aged rats underwent a unilateral distal permanent middle cerebral artery occlusion and one week later were treated with an anti-Nogo-A or control antibody. Nine weeks post-stroke, treated rats and normal aged rats were tested on the Morris water maze task. Following testing rats were sacrificed and brains processed for the Golgi-Cox method. Hippocampal CA3 and CA1 pyramidal and dentate gyrus granule cells were examined for dendritic length and number of branch segments, and CA3 and CA1 pyramidal cells were examined for spine density and morphology. Anti-Nogo-A immunotherapy given one week following stroke in aged rats improved performance on the reference memory portion of the Morris water maze task. However, this improved performance was not correlated with structural changes in the hippocampal neurons examined. Our finding of improved performance on the Morris water maze in aged rats after stroke and treatment with anti-Nogo-A immunotherapy demonstrates the promising therapeutic potential for anti-Nogo-A immunotherapy to treat cognitive deficits after stroke. The identification of sites of axonal and dendritic plasticity in the aged brain after stroke and treatment with anti-Nogo-A immunotherapy is still under investigation.",,"['Gillani, Rebecca L.', 'Tsai, Shih-Yen', 'Wallace, Douglas G.', 'O’Brien, Timothy E.', 'Arhebamen, Ebinehita', 'Tole, Mateo', 'Schwab, Martin E.', 'Kartje, Gwendolyn L.']",,,,
,PMC,"IFITM Proteins Mediate the Innate Immune Response to Influenza A H1N1 Virus, West Nile Virus and Dengue Virus",http://dx.doi.org/10.1016/j.cell.2009.12.017,PMC2824905,,,"Influenza viruses exploit host cell machinery to replicate, resulting in epidemics of respiratory illness. In turn, the host expresses anti-viral restriction factors to defend against infection. To find host-cell modifiers of influenza A H1N1 viral infection, we used a functional genomic screen and identified over 120 influenza A virus-dependency factors with roles in endosomal acidification, vesicular trafficking, mitochondrial metabolism and RNA splicing. We discovered that the interferon-inducible trans-membrane proteins, IFITM1, 2 and 3, restrict an early step in influenza A viral replication. The IFITM proteins confer basal resistance to influenza A virus, but are also inducible by interferons type I and II, and are critical for interferon's virustatic actions. Further characterization revealed that the IFITM proteins inhibit the early replication of flaviviruses, including dengue virus and West Nile virus. Collectively this work identifies a new family of anti-viral restriction factors that mediate cellular resistance to at least three major human pathogens.",,"['Brass, Abraham L.', 'Huang, I-Chueh', 'Benita, Yair', 'John, Sinu P.', 'Krishnan, Manoj N.', 'Feeley, Eric M.', 'Ryan, Bethany', 'Weyer, Jessica L.', 'van der Weyden, Louise', 'Fikrig, Erol', 'Adams, David J.', 'Xavier, Ramnik J.', 'Farzan, Michael', 'Elledge, Stephen J.']",,,,
,PMC,Enhancement of Antiviral Activity of Collectin Trimers through Cross-Linking and Mutagenesis of the Carbohydrate Recognition Domain,http://dx.doi.org/10.1159/000272313,PMC2956016,,,"Surfactant protein D (SP-D) plays important roles in innate defense against respiratory viruses [including influenza A viruses (IAVs)]. Truncated trimers composed of its neck and carbohydrate recognition domains (NCRDs) bind various ligands; however, they have minimal inhibitory activity for IAV. We have sought to find ways to increase the antiviral activity of collectin NCRDs. Cross-linking of the SP-D NCRD with nonblocking monoclonal antibodies (mAbs) markedly potentiates antiviral activity. In the present report, we demonstrate that F(ab’)2 [but not F(ab’)1] fragments of a cross-linking mAb have similar effects. Hence, cross-linking activity, but not the Fc domain of the mAb, is needed for increased antiviral activity. In contrast, the Fc domain of the mAb was important for increasing viral uptake or respiratory burst responses of human neutrophils. Our NCRD constructs contain an S protein binding site. Herein, we show that a multivalent S protein complex caused cross-linking and also increased the antiviral activity of NCRDs. NCRDs of conglutinin and CL43 had greater intrinsic antiviral activity than those of SP-D or mannose-binding lectin. Based on motifs found in these serum collectins, we have constructed mutant versions of the human SP-D NCRD that have increased antiviral activity. These mutant NCRDs also had potentiated activity after cross-linking with F(ab’)2 fragments or S protein complexes. Hence, the antiviral activity of NCRDs can be increased by 2 distinct, complementary strategies, namely cross-linking of NCRDs through various means and mutagenesis of CRD residues to increase viral binding. These findings may be relevant for antiviral therapy.",,"['White, Mitchell R.', 'Boland, Patrick', 'Tecle, Tesfaldet', 'Gantz, Donald', 'Sorenson, Grith', 'Tornoe, Ida', 'Holmskov, Uffe', 'McDonald, Barbara', 'Crouch, Erika C.', 'Hartshorn, Kevan L.']",,,,
,PMC,Broad-Spectrum In Vitro Activity and In Vivo Efficacy of the Antiviral Protein Griffithsin against Emerging Viruses of the Family Coronaviridae,http://dx.doi.org/10.1128/JVI.02322-09,PMC2820936,,,"Viruses of the family Coronaviridae have recently emerged through zoonotic transmission to become serious human pathogens. The pathogenic agent responsible for severe acute respiratory syndrome (SARS), the SARS coronavirus (SARS-CoV), is a member of this large family of positive-strand RNA viruses that cause a spectrum of disease in humans, other mammals, and birds. Since the publicized outbreaks of SARS in China and Canada in 2002-2003, significant efforts successfully identified the causative agent, host cell receptor(s), and many of the pathogenic mechanisms underlying SARS. With this greater understanding of SARS-CoV biology, many researchers have sought to identify agents for the treatment of SARS. Here we report the utility of the potent antiviral protein griffithsin (GRFT) in the prevention of SARS-CoV infection both in vitro and in vivo. We also show that GRFT specifically binds to the SARS-CoV spike glycoprotein and inhibits viral entry. In addition, we report the activity of GRFT against a variety of additional coronaviruses that infect humans, other mammals, and birds. Finally, we show that GRFT treatment has a positive effect on morbidity and mortality in a lethal infection model using a mouse-adapted SARS-CoV and also specifically inhibits deleterious aspects of the host immunological response to SARS infection in mammals.",,"[""O'Keefe, Barry R."", 'Giomarelli, Barbara', 'Barnard, Dale L.', 'Shenoy, Shilpa R.', 'Chan, Paul K. S.', 'McMahon, James B.', 'Palmer, Kenneth E.', 'Barnett, Brian W.', 'Meyerholz, David K.', 'Wohlford-Lenane, Christine L.', 'McCray, Paul B.']",,,,
,PMC,Exploring Peptide Mimics for the Production of Antibodies Against Discontinuous Protein Epitopes,http://dx.doi.org/10.1016/j.molimm.2009.10.015,PMC2821332,,,"Peptide “mimics” (mimotopes) of linear protein epitopes and carbohydrate epitopes have been successfully used as immunogens to elicit cross-reactive antibodies against their cognate epitopes; however, immunogenic mimicry has been difficult to achieve for discontinuous protein epitopes. To explore this, we developed from phage-displayed peptide libraries optimized peptide mimics for three well-characterized discontinuous epitopes on hen egg lysozyme and horse cytochrome C. The peptides competed with their cognate antigens for antibody binding, displayed affinities in the nM range, and shared critical binding residues with their native epitopes. Yet, while immunogenic, none of the peptides elicited antibodies that cross-reacted with their cognate antigens. We analyzed the 3-D structure of the site within each discontinuous epitope that shared critical binding residues with its peptide mimic, and observed that in each case it formed a ridge-like patch on the epitope; in no case did it cover most or all of the epitope. Thus, the peptides’ lack of immunogenic mimicry could be attributed to their inability to recapitulate the topological features of their cognate epitopes. Our results suggest that direct peptide immunizations are not a practical strategy for generating targeted antibody responses against discontinuous epitopes.",,"['Irving, Melita B.', 'Craig, Lisa', 'Menendez, Alfredo', 'Gangadhar, Beechanahalli P.', 'Montero, Marinieve', 'van Houten, Nienke E.', 'Scott, Jamie K.']",,,,
,PMC,Biological importance of marine algae,http://dx.doi.org/10.1016/j.jsps.2009.12.001,PMC3731014,,,"Marine organisms are potentially prolific sources of highly bioactive secondary metabolites that might represent useful leads in the development of new pharmaceutical agents. Algae can be classified into two main groups; first one is the microalgae, which includes blue green algae, dinoflagellates, bacillariophyta (diatoms)… etc., and second one is macroalgae (seaweeds) which includes green, brown and red algae. The microalgae phyla have been recognized to provide chemical and pharmacological novelty and diversity. Moreover, microalgae are considered as the actual producers of some highly bioactive compounds found in marine resources. Red algae are considered as the most important source of many biologically active metabolites in comparison to other algal classes. Seaweeds are used for great number of application by man. The principal use of seaweeds as a source of human food and as a source of gums (phycocollides). Phycocolloides like agar agar, alginic acid and carrageenan are primarily constituents of brown and red algal cell walls and are widely used in industry.",,"El Gamal, Ali A.",,,,
,PMC,Reconstructing influenza incidence by deconvolution of daily mortality time series,http://dx.doi.org/10.1073/pnas.0902958106,PMC2796142,,,"We propose a mathematically straightforward method to infer the incidence curve of an epidemic from a recorded daily death curve and time-to-death distribution; the method is based on the Richardson–Lucy deconvolution scheme from optics. We apply the method to reconstruct the incidence curves for the 1918 influenza epidemic in Philadelphia and New York State. The incidence curves are then used to estimate epidemiological quantities, such as daily reproductive numbers and infectivity ratios. We found that during a brief period before the official control measures were implemented in Philadelphia, the drop in the daily number of new infections due to an average infector was much larger than expected from the depletion of susceptibles during that period; this finding was subjected to extensive sensitivity analysis. Combining this with recorded evidence about public behavior, we conclude that public awareness and change in behavior is likely to have had a major role in the slowdown of the epidemic even in a city whose response to the 1918 influenza epidemic is considered to have been among the worst in the U.S.",,"['Goldstein, Edward', 'Dushoff, Jonathan', 'Ma, Junling', 'Plotkin, Joshua B.', 'Earn, David J. D.', 'Lipsitch, Marc']",,,,
,PMC,The Struggle Against Pandemic Influenza A (H1N1) 2009,,PMC3074803,,,,,"Balkhair, Abdullah",,,,
,PMC,Segmented Helical Structure of the Neck Region of the Glycan-Binding Receptor DC-SIGNR,http://dx.doi.org/10.1016/j.jmb.2009.10.006,PMC2971551,19835887,CC BY,"Carbohydrate-recognition domains (CRDs) in the glycan-binding receptors DC-SIGN (dendritic-cell-specific intercellular adhesion molecule 1-grabbing nonintegrin; CD209) and DC-SIGNR (DC-SIGN-related receptor, also known as L-SIGN and variously designated CD209L and CD299) are projected from the membrane surface by extended neck domains containing multiple repeats of a largely conserved 23-amino-acid sequence motif. Crystals of a fragment of the neck domain of DC-SIGNR containing multiple repeats in which each molecule extends through multiple unit cells, such that the observed crystallographic asymmetric unit represents one repeat averaged over six repeats of the protein, have been obtained. The repeats are largely α-helical. Based on the structure and arrangement of the repeats in the crystal, the neck region can be described as a series of four-helix bundles connected by short, non-helical linkers. Combining the structure of the isolated neck domain with a previously determined overlapping structure of the distal end of the neck region with the CRDs attached provides a model of the almost-complete extracellular portion of the receptor. The results are consistent with previous characterization of the extended structure for the isolated neck region and the extracellular domain. The organization of the neck suggests how CRDs may be disposed differently in DC-SIGN compared with DC-SIGNR and in variant forms of DC-SIGNR assembled from polypeptides with different numbers of repeats in the neck domain.",2009 Dec 11,"['Feinberg, Hadar', 'Tso, Cynthia K.W.', 'Taylor, Maureen E.', 'Drickamer, Kurt', 'Weis, William I.']",J Mol Biol,,,
,PMC,The immune response during acute HIV-1 infection: clues for vaccine development,http://dx.doi.org/10.1038/nri2674,PMC3119211,,,"The early immune response to HIV-1 infection is likely to be an important factor in determining the clinical course of disease. Recent data indicate that the HIV-1 quasispecies that arise following a mucosal infection are usually derived from a single transmitted virus. Moreover, the finding that the first effective immune responses drive the selection of virus escape mutations provides insight into the earliest immune responses against the transmitted virus and their contributions to the control of acute viraemia. Strong innate and adaptive immune responses occur subsequently but they are too late to eliminate the infection. In this Review, we discuss recent studies on the kinetics and quality of early immune responses to HIV-1 and their implications for developing a successful preventive HIV-1 vaccine.",,"['McMichael, Andrew J.', 'Borrow, Persephone', 'Tomaras, Georgia D.', 'Goonetilleke, Nilu', 'Haynes, Barton F.']",,,,
,PMC,Emergence and re-emergence of viral diseases of the central nervous system,http://dx.doi.org/10.1016/j.pneurobio.2009.12.003,PMC2860042,,,"Neurologic disease is a major cause of disability in resource-poor countries and a substantial portion of this disease is due to infections of the CNS. A wide variety of emerging and re-emerging viruses contribute to this disease burden. New emerging infections are commonly due to RNA viruses that have expanded their geographic range, spread from animal reservoirs or acquired new neurovirulence properties. Mosquito-borne viruses with expanding ranges include West Nile virus, Japanese encephalitis virus and Chikungunya virus. Zoonotic viruses that have recently crossed into humans to cause neurologic disease include the bat henipaviruses Nipah and Hendra, as well as the primate-derived human immunodeficiency virus. Viruses adapt to new hosts, or to cause more severe disease, by changing their genomes through reassortment (e.g. influenza virus), mutation (essentially all RNA viruses) and recombination (e.g. vaccine strains of poliovirus). Viruses that appear to have recently become more neurovirulent include West Nile virus, enterovirus 71 and possibly Chikungunya virus. In addition to these newer challenges, rabies, polio and measles all remain important causes of neurologic disease despite good vaccines and global efforts toward control. Control of human rabies depends on elimination of rabies in domestic dogs through regular vaccination. Poliovirus eradication is challenged by the ability of the live attenuated vaccine strains to revert to virulence during the prolonged period of gastrointestinal replication. Measles elimination depends on delivery of two doses of live virus vaccine to a high enough proportion of the population to maintain herd immunity for this highly infectious virus.",,"Griffin, Diane E.",,,,
,PMC,8-pCPT-cGMP stimulates αβγ-ENaC activity in oocytes as an external ligand requiring specific nucleotide moieties,http://dx.doi.org/10.1152/ajprenal.00307.2009,PMC2822513,,,"Epithelial sodium channels (ENaC) are regulated by protein kinase A, in addition to a broad spectrum of other protein kinases. It is not clear whether cGMP/PKG signaling might regulate ENaC activity. We examined the responses of αβγ-ENaC channels expressed in Xenopus oocytes to 8-(4-chlorophenylthio)-cGMP (8-pCPT-cGMP), a cell-permeable cGMP analog. This compound stimulated human αβγ-ENaC activity in a dose-dependent fashion, but cell-impermeable cGMP had no effect. Similar stimulatory effects of cGMP were observed in oocytes expressing either mouse or rat αβγ-ENaC channels. The identical ion selectivity and amiloride sensitivity of the 8-pCPT-cGMP-activated currents to those of αβγ-ENaC channels suggest that the cGMP-activated currents are associated with expressed ENaC. The PKGI activator Sp isomer of β-phenyl-1,N(2)-etheno-8-bromo-cGMP did not elicit a rise in ENaC current and that the 8-pCPT-cGMP-induced activation of ENaC channels was blocked by incubating oocytes with a PKG inhibitor, but not with other cGMP-sensitive kinase inactivators for PKA, MEK, MAP, and PKC. Surprisingly, both site-directed mutation of putative consensus PKG phosphorylation sites and truncation of entire cytosolic NH(2)- and COOH-terminal tails did not alter the response to 8-pCPT-cGMP. The ENaC activity was activated to the same extent by 8-pCPT-cGMP in cells in which PKGII expression was knocked down using small interfering RNA. Analog to 8-CPT-cAMP, 8-pCPT-cGMP was capable of activating ENaC in the identical manner in cell-free outside-out patches. We conclude that the rapid upregulation of human αβγ-ENaC activity in oocytes by external 8-pCPT-cGMP and 4-chlorothiolphenol-cAMP depends on the para-chlorophenylthiol and the hydroxy groups, and 8-pCPT-cGMP may serve as a novel ENaC ligand in addition to activating PKG signal.",,"['Nie, Hong-Guang', 'Zhang, Wei', 'Han, Dong-Yun', 'Li, Qing-Nan', 'Li, Jun', 'Zhao, Run-Zhen', 'Su, Xue-Feng', 'Peng, Ji-Bin', 'Ji, Hong-Long']",,,,
,PMC,Neuronal Degeneration in a Viral Model of Multiple Sclerosis,http://dx.doi.org/10.1523/JNEUROSCI.5198-09.2009,PMC6666118,,,,,"Schneider, Raphael",,,,
,PMC,Dynamics of Coronavirus Replication-Transcription Complexes,http://dx.doi.org/10.1128/JVI.01716-09,PMC2812403,,,"Coronaviruses induce in infected cells the formation of double-membrane vesicles (DMVs) in which the replication-transcription complexes (RTCs) are anchored. To study the dynamics of these coronavirus replicative structures, we generated recombinant murine hepatitis coronaviruses that express tagged versions of the nonstructural protein nsp2. We demonstrated by using immunofluorescence assays and electron microscopy that this protein is recruited to the DMV-anchored RTCs, for which its C terminus is essential. Live-cell imaging of infected cells demonstrated that small nsp2-positive structures move through the cytoplasm in a microtubule-dependent manner. In contrast, large fluorescent structures are rather immobile. Microtubule-mediated transport of DMVs, however, is not required for efficient replication. Biochemical analyses indicated that the nsp2 protein is associated with the cytoplasmic side of the DMVs. Yet, no recovery of fluorescence was observed when (part of) the nsp2-positive foci were bleached. This result was confirmed by the observation that preexisting RTCs did not exchange fluorescence after fusion of cells expressing either a green or a red fluorescent nsp2. Apparently, nsp2, once recruited to the RTCs, is not exchanged with nsp2 present in the cytoplasm or at other DMVs. Our data show a remarkable resemblance to results obtained recently by others with hepatitis C virus. The observations point to intriguing and as yet unrecognized similarities between the RTC dynamics of different plus-strand RNA viruses.",,"['Hagemeijer, Marne C.', 'Verheije, Monique H.', 'Ulasli, Mustafa', 'Shaltiël, Indra A.', 'de Vries, Lisa A.', 'Reggiori, Fulvio', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.']",,,,
,PMC,An N-Terminal Region of Lassa Virus L Protein Plays a Critical Role in Transcription but Not Replication of the Virus Genome,http://dx.doi.org/10.1128/JVI.01657-09,PMC2812395,,,"The central domain of the 200-kDa Lassa virus L protein is a putative RNA-dependent RNA polymerase. N- and C-terminal domains may harbor enzymatic functions important for viral mRNA synthesis, including capping enzymes or cap-snatching endoribonucleases. In the present study, we have employed a large-scale mutagenesis approach to map functionally relevant residues in these regions. The main targets were acidic (Asp and Glu) and basic residues (Lys and Arg) known to form catalytic and binding sites of capping enzymes and endoribonucleases. A total of 149 different mutants were generated and tested in the Lassa virus replicon system. Nearly 25% of evolutionarily highly conserved acidic and basic side chains were dispensable for function of L protein in the replicon context. The vast majority of the remaining mutants had defects in both transcription and replication. Seven residues (Asp-89, Glu-102, Asp-119, Lys-122, Asp-129, Glu-180, and Arg-185) were selectively important for mRNA synthesis. The phenotype was particularly pronounced for Asp-89, Glu-102, and Asp-129, which were indispensable for transcription but could be replaced by a variety of amino acid residues without affecting genome replication. Bioinformatics disclosed the remote similarity of this region to type IIs endonucleases. The mutagenesis was complemented by experiments with the RNA polymerase II inhibitor α-amanitin, demonstrating dependence of viral transcription from the cellular mRNA pool. In conclusion, this paper describes an N-terminal region in L protein being important for mRNA, but not genome synthesis. Bioinformatics and cell biological experiments lend support to the hypothesis that this region could be part of a cap-snatching enzyme.",,"['Lelke, Michaela', 'Brunotte, Linda', 'Busch, Carola', 'Günther, Stephan']",,,,
,PMC,A Single Tyrosine in the Severe Acute Respiratory Syndrome Coronavirus Membrane Protein Cytoplasmic Tail Is Important for Efficient Interaction with Spike Protein,http://dx.doi.org/10.1128/JVI.02458-09,PMC2812384,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes 3 major envelope proteins: spike (S), membrane (M), and envelope (E). Previous work identified a dibasic endoplasmic reticulum retrieval signal in the cytoplasmic tail of SARS-CoV S that promotes efficient interaction with SARS-CoV M. The dibasic signal was shown to be important for concentrating S near the virus assembly site rather than for direct interaction with M. Here, we investigated the sequence requirements of the SARS-CoV M protein that are necessary for interaction with SARS-CoV S. The SARS-CoV M tail was shown to be necessary for S localization in the Golgi region when the proteins were exogenously coexpressed in cells. This was specific, since SARS-CoV M did not retain an unrelated glycoprotein in the Golgi. Importantly, we found that an essential tyrosine residue in the SARS-CoV M cytoplasmic tail, Y(195), was important for S-M interaction. When Y(195) was mutated to alanine, M(Y195A) no longer retained S intracellularly at the Golgi. Unlike wild-type M, M(Y195A) did not reduce the amount of SARS-CoV S carbohydrate processing or surface levels when the two proteins were coexpressed. Mutating Y(195) also disrupted SARS-CoV S-M interaction in vitro. These results suggest that Y(195) is necessary for efficient SARS-CoV S-M interaction and, thus, has a significant involvement in assembly of infectious virus.",,"['McBride, Corrin E.', 'Machamer, Carolyn E.']",,,,
,PMC,The Murine Coronavirus Nucleocapsid Gene Is a Determinant of Virulence,http://dx.doi.org/10.1128/JVI.01758-09,PMC2812375,,,"The murine coronavirus, mouse hepatitis virus (MHV) strain A59, causes acute encephalitis and chronic demyelinating disease as well as hepatitis in mice. The JHM strain (also called MHV-4 or JHM.SD) causes fatal encephalitis and only minimal hepatitis. Previous analysis of chimeric recombinant MHVs in which the spike gene, encoding the protein that mediates viral entry and cell-to-cell fusion, was exchanged between JHM and A59 showed that the spike plays a major role in determining organ tropism and neurovirulence but that other genes also play important roles in pathogenic outcome. Here, we have investigated the role of the nucleocapsid protein in MHV-induced disease. The multifunctional nucleocapsid protein is complexed with the genomic RNA, interacts with the viral membrane protein during virion assembly, and plays an import role in enhancing the efficiency of transcription. A pair of chimeric recombinant viruses in which the nucleocapsid gene was exchanged between JHM and A59 was selected and compared to wild-type parental strains in terms of virulence. Importantly, expression of the JHM nucleocapsid in the context of the A59 genome conferred increased mortality and spread of viral antigen in the mouse central nervous system compared to the parental A59 strain, while having little effect on the induction of hepatitis. While the JHM nucleocapsid did not appear to enhance neuron-to-neuron spread in primary neuronal cultures, the increased neurovirulence it conferred may be due in part to the induction of a less robust T-cell response than that induced by strain A59.",,"['Cowley, Timothy J.', 'Long, Simon Y.', 'Weiss, Susan R.']",,,,
,PMC,Z Proteins of New World Arenaviruses Bind RIG-I and Interfere with Type I Interferon Induction,http://dx.doi.org/10.1128/JVI.01362-09,PMC2812374,,,"The retinoic acid-inducible gene I product (RIG-I) is a cellular sensor of RNA virus infection that regulates the cellular beta interferon (IFN-β) response. The nucleoproteins (NP) of arenaviruses are reported to antagonize the IFN response by inhibiting interferon regulatory factor 3 (IRF-3). Here, we demonstrate that the Z proteins of four New World (NW) arenaviruses, Guanarito virus (GTOV), Junin virus (JUNV), Machupo virus (MAVC), and Sabia virus (SABV), bind to RIG-I, resulting in downregulation of the IFN-β response. We show that expression of the four NW arenavirus Z proteins inhibits IFN-β mRNA induction in A549 cells in response to RNA bearing 5′ phosphates (5′pppRNA). NW arenavirus Z proteins interact with RIG-I in coimmunoprecipitation studies and colocalize with RIG-I. Furthermore, expression of Z proteins interferes with the interaction between RIG-I and MAVS. Z expression also impedes the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and IRF-3 activation. Our results indicate that NW arenavirus Z proteins, but not Z protein of the Old World (OW) arenavirus lymphocytic choriomeningitis virus (LCMV) or Lassa virus, bind to RIG-I and inhibit downstream activation of the RIG-I signaling pathway, preventing the transcriptional induction of IFN-β.",,"['Fan, Lina', 'Briese, Thomas', 'Lipkin, W. Ian']",,,,
,PMC,"The development, optimization and validation of an assay for high throughput antiviral drug screening against Dengue virus",,PMC2802053,,,"Dengue virus (DENV) is listed as one of the NIAID Category A priority pathogens. Dengue disease is endemic in most tropical countries, with an estimated 2.5 billion people living in areas at risk of DENV infection. Due to the lack of vaccines and antiviral drugs, it is now a huge public health burden around the world. In order to screen large compound libraries for the identification of novel antivirals targeting DENV, it is essential to develop a high throughput screening (HTS) amenable assay. Here, we present the development, optimization and validation of a cytopathic effect-based assay against Dengue virus serotype-2 (DENV-2). The assay conditions, including cell culturing conditions, DMSO tolerance and the multiplicity of infection, were optimized in both 96- and 384-well plates. Assay robustness and reproducibility were determined under the optimized conditions in 96-well plate, including Z'-value of 0.71, signal-to-background ratio of 6.88, coefficient of variation of 6.3% in mock-infected cells and 12.3% in DENV-2 infected cells. This assay was further miniaturized into a 384-well plate format with similar assay robustness and reproducibility comparing with these in the 96-well plate format. This assay was then validated using the LOPAC(1280) compound library, demonstrating its repeatability with comparable assay robustness and reproducibility. This fully developed and validated HTS amenable assay could be used in future studies to screen large compound libraries for the identification of novel antivirals against dengue disease.",,"['Che, Pulin', 'Wang, Lihua', 'Li, Qianjun']",,,,
,PMC,Human parainfluenza virus type 2 V protein inhibits interferon production and signaling and is required for replication in non-human primates,http://dx.doi.org/10.1016/j.virol.2009.11.018,PMC2822077,,,"In wild-type human parainfluenza virus type 2 (WT HPIV2), one gene (the P/V gene) encodes both the polymerase-associated phosphoprotein (P) and the accessory V protein. We generated a HPIV2 virus (rHPIV2-V(ko)) in which the P/V gene encodes only the P protein to examine the role of V in replication in vivo and as a potential live attenuated virus vaccine. Preventing expression of V protein severely impaired virus recovery from cDNA and growth in vitro, particularly in IFN-competent cells. rHPIV2-V(ko), unlike WT HPIV2, strongly induced IFN-β and permitted IFN signaling, leading to establishment of a robust antiviral state. rHPIV2-V(ko) infection induced extensive syncytia and cytopathicity that was due to both apoptosis and necrosis. Replication of rHPIV2-V(ko) was highly restricted in the respiratory tract of African green monkeys and in differentiated primary human airway epithelial (HAE) cultures, suggesting that V protein is essential for efficient replication of HPIV2 in organized epithelial cells and that rHPIV2-V(ko) is over-attenuated for use as a live attenuated vaccine.",,"['Schaap-Nutt, Anne', 'D’Angelo, Christopher', 'Scull, Margaret A.', 'Amaro-Carambot, Emerito', 'Nishio, Machiko', 'Pickles, Raymond J.', 'Collins, Peter L.', 'Murphy, Brian R.', 'Schmidt, Alexander C.']",,,,
,PMC,Evolution and public health,http://dx.doi.org/10.1073/pnas.0906198106,PMC2868289,,,"Evolution and its elements of natural selection, population migration, genetic drift, and founder effects have shaped the world in which we practice public health. Human cultures and technologies have modified life on this planet and have coevolved with myriad other species, including microorganisms; plant and animal sources of food; invertebrate vectors of disease; and intermediate hosts among birds, mammals, and nonhuman primates. Molecular mechanisms of differential resistance or susceptibility to infectious agents or diets have evolved and are being discovered with modern methods. Some of these evolutionary relations require a perspective of tens of thousands of years, whereas other changes are observable in real time. The implications and applications of evolutionary understanding are important to our current programs and policies for infectious disease surveillance, gene–environment interactions, and health disparities globally.",,"Omenn, Gilbert S.",,,,
,PMC,Epidemic dynamics at the human-animal interface,http://dx.doi.org/10.1126/science.1177345,PMC3891603,,,"Few infectious diseases are entirely human-specific: most human pathogens also circulate in animals, or else originated in non-human hosts. Influenza, plague, and trypanosomiasis are classic examples of zoonoses, or infections that transmit from animals to humans. The multi-host ecology of zoonoses leads to complex dynamics, and analytical tools such as mathematical modeling are vital to the development of effective control policies and research agendas. Much attention has focused on modeling pathogens with simpler life cycles and immediate global urgency, such as influenza and SARS, but vector-transmitted, chronic, and protozoan infections have been neglected, as have crucial processes such as cross-species transmission. Progress in understanding and combating zoonoses requires a new generation of models that addresses a broader set of pathogen life histories and integrates across host species and scientific disciplines.",,"['Lloyd-Smith, James O.', 'George, Dylan', 'Pepin, Kim M.', 'Pitzer, Virginia E.', 'Pulliam, Juliet R. C.', 'Dobson, Andrew P.', 'Hudson, Peter J.', 'Grenfell, Bryan T.']",,,,
,PMC,Seroprevalences to Viral Pathogens in Free-Ranging and Captive Cheetahs (Acinonyx jubatus) on Namibian Farmland,http://dx.doi.org/10.1128/CVI.00345-09,PMC2815525,,,"Cheetah populations are diminishing rapidly in their natural habitat. One reason for their decline is thought to be a high susceptibility to (infectious) diseases because cheetahs in zoos suffer from high disease-induced mortality. Data on the health status of free-ranging cheetahs are scarce, and little is known about their exposure and susceptibility to infectious diseases. We determined seroprevalences to nine key viruses (feline herpesvirus 1, feline calicivirus, feline parvovirus, feline coronavirus, canine distemper virus, feline immunodeficiency virus [FIV], puma lentivirus, feline leukemia virus, and rabies virus) in 68 free-ranging cheetahs on east-central Namibian farmland, 24 nonvaccinated Namibian captive cheetahs, and several other wild carnivore species and conducted necropsies of cheetahs and other wild carnivores. Eight of 11 other wild carnivores were seropositive for at least one of the viruses, including the first record of an FIV-like infection in a wild felid west of the Kalahari, the caracal (Felis caracal). Seroprevalences of the free-ranging cheetahs were below 5% for all nine viruses, which is significantly lower than seroprevalences in nonvaccinated captive cheetahs and those for five of seven viruses in previously studied free-ranging cheetahs from north-central Namibia (L. Munson, L. Marker, E. Dubovi, J. A. Spencer, J. F. Evermann, and S. J. O'Brien, J. Wildl. Dis. 40:23-31, 2004). There was no clinical or pathological evidence of infectious diseases in living or dead cheetahs. The results suggest that while free-ranging wild carnivores may be a source of pathogens, the distribution of seroprevalences across studies mirrored local human population density and factors associated with human habitation, probably reflecting contact opportunities with (nonvaccinated) domestic and feral cats and dogs. They also suggest that Namibian cheetahs respond effectively to viral challenges, encouraging consistent and sustainable conservation efforts.",,"['Thalwitzer, Susanne', 'Wachter, Bettina', 'Robert, Nadia', 'Wibbelt, Gudrun', 'Müller, Thomas', 'Lonzer, Johann', 'Meli, Marina L.', 'Bay, Gert', 'Hofer, Heribert', 'Lutz, Hans']",,,,
,PMC,Coronavirus Nucleocapsid Protein Facilitates Template Switching and Is Required for Efficient Transcription,http://dx.doi.org/10.1128/JVI.02011-09,PMC2812394,,,"Purified nucleocapsid protein (N protein) from transmissible gastroenteritis virus (TGEV) enhanced hammerhead ribozyme self-cleavage and favored nucleic acid annealing, properties that define RNA chaperones, as previously reported. Several TGEV N-protein deletion mutants were expressed in Escherichia coli and purified, and their RNA binding ability and RNA chaperone activity were evaluated. The smallest N-protein domain analyzed with RNA chaperone activity, facilitating DNA and RNA annealing, contained the central unstructured region (amino acids 117 to 268). Interestingly, N protein and its deletion mutants with RNA chaperone activity enhanced template switching in a retrovirus-derived heterologous system, reinforcing the concept that TGEV N protein is an RNA chaperone that could be involved in template switching. This result is in agreement with the observation that in vivo, N protein is not necessary for TGEV replication, but it is required for efficient transcription.",,"['Zúñiga, Sonia', 'Cruz, Jazmina L. G.', 'Sola, Isabel', 'Mateos-Gómez, Pedro A.', 'Palacio, Lorena', 'Enjuanes, Luis']",,,,
,PMC,Effects of aging on the adaptive immune response to respiratory virus infections,http://dx.doi.org/10.2217/ahe.09.69,PMC2822389,,,"Severe acute respiratory disease caused by respiratory virus infections in individuals aged 65 years and older and in high-risk adults, such as those with chronic cardiopulmonary disorders, is associated with increased hospitalization and mortality rates. Epidemiological studies have identified influenza virus and respiratory syncytial virus as the most frequent causes of virus-induced respiratory disease in elderly and high-risk adults. Studies in both humans and animal models have established fundamental defects in cell-mediated and humoral immune responses in aged individuals. However, it is not well understood how age specifically alters the immune response to respiratory pathogens. In this review, we will focus our discussion on the major causative agents of severe respiratory virus infections in elderly and high-risk adults and the age-associated defects in the immune response that probably contribute to the increased disease severity observed in these populations.",,"['Fulton, Ross B', 'Varga, Steven M']",,,,
,PMC,Systemic Dendritic Cell Mobilization Associated with Administration of FLT3 Ligand to SIV- and SHIV-Infected Macaques,http://dx.doi.org/10.1089/aid.2009.0053,PMC2828165,,,"Reports indicate that myeloid and plasmacytoid dendritic cells (mDCs and pDCs), which are key effector cells in host innate immune responses, can be infected with HIV-1 and are reduced in number and function during the chronic phase of HIV disease. Furthermore, it was recently demonstrated that a sustained loss of mDCs and pDCs occurs in SIV-infected macaques. Since loss of functional DC populations might impair innate immune responses to opportunistic microorganisms and neoplastic cells, we explored whether inoculation of naive and SIV- or SHIV-infected pigtailed macaques with the hematopoietic cytokine FLT3-ligand (FLT3-L) would expand the number of mDCs and pDCs in vivo. After the macaques received supraphysiologic doses of FLT3-L, mDCs, pDCs, and monocytes increased up to 45-fold in blood, lymph nodes, and bone marrow (BM), with DC expansion in the BM preceding mobilization in blood and lymphoid tissues. FLT3-L also increased serum levels of IL-12, at least transiently, and elicited higher surface expression of HLA-DR and the activation markers CD25 and CD69 on NK and T cells. During and after treatment of infected animals, APCs increased in number and were activated; however, CD4(+) T cell numbers, virion RNA, and anti-SIV/SHIV antibody titers remained relatively stable, suggesting that FLT3-L might be a safe modality to expand DC populations and provide therapeutic benefit during chronic lentivirus infections.",,"['Reeves, R. Keith', 'Wei, Qing', 'Stallworth, Jackie', 'Fultz, Patricia N.']",,,,
,PMC,"Anatomical distribution of avian bornavirus in parrots, its occurrence in clinically healthy birds and ABV-antibody detection",http://dx.doi.org/10.1080/03079450903349238,PMC4109277,,,"Proventricular dilatation disease (PDD) is a fatal infectious disease of birds that primarily affects psittacine birds. Although a causative agent has not been formally demonstrated, the leading candidate is a novel avian bornavirus (ABV) detected in post-mortem tissue samples of psittacids with PDD from the USA, Israel and, recently, Germany. Here we describe the presence of ABV in a parrot with PDD as well as in clinically normal birds exposed to birds with PDD. In two ABV-positive post-mortem cases, the tissue distribution of ABV was investigated by quantitative real-time reverse transcription-polymerase chain reaction. Viraemia was observed in a PDD-affected bird whereas a restriction of ABV to nerve tissue was found in the non- PDD-affected bird. Healthy birds from the same aviary as the affected birds were also found to harbour the virus; 19/59 (32.2%) birds tested positive for ABV RNA in cloacal swabs, providing the first evidence of ABV in clinically healthy birds. In contrast, 39 birds from the same geographic area, but from two different aviaries without PDD cases in recent years, had negative cloacal swabs. ABV RNA-positive, clinically healthy birds demonstrated the same serological response as the animal with confirmed PDD. These results indicate that ABV infection may occur without clinical evidence of PDD and suggest that cloacal swabs can enable the non-invasive detection of ABV infection.",,"['Lierz, Michael', 'Hafez, Hafez M.', 'Honkavuori, Kirsi S.', 'Gruber, Achim D.', 'Olias, Philipp', 'Abdelwhab, Elsayed M.', 'Kohls, Andrea', 'Lipkin, W. Ian', 'Briese, Thomas', 'Hauck, Ruediger']",,,,
,PMC,Exposure to Bioterrorism and Mental Health Response among Staff on Capitol Hill,http://dx.doi.org/10.1089/bsp.2009.0031,PMC2956562,,,"The October 2001 anthrax attacks heralded a new era of bioterrorism threat in the U.S. At the time, little systematic data on mental health effects were available to guide authorities' response. For this study, which was conducted 7 months after the anthrax attacks, structured diagnostic interviews were conducted with 137 Capitol Hill staff workers, including 56 who had been directly exposed to areas independently determined to have been contaminated. Postdisaster psychopathology was associated with exposure; of those with positive nasal swab tests, PTSD was diagnosed in 27% and any post-anthrax psychiatric disorder in 55%. Fewer than half of those who were prescribed antibiotics completed the entire course, and only one-fourth had flawless antibiotic adherence. Thirty percent of those not exposed believed they had been exposed; 18% of all study participants had symptoms they suspected were symptoms of anthrax infection, and most of them sought medical care. Extrapolation of raw numbers to large future disasters from proportions with incorrect belief in exposure in this limited study indicates a potential for important public health consequences, to the degree that people alter their healthcare behavior based on incorrect exposure beliefs. Incorrect belief in exposure was associated with being very upset, losing trust in health authorities, having concerns about mortality, taking antibiotics, and being male. Those who incorrectly believe they were exposed may warrant concern and potential interventions as well as those exposed. Treatment adherence and maintenance of trust for public health authorities may be areas of special concern, warranting further study to inform authorities in future disasters involving biological, chemical, and radiological agents.",,"['North, Carol S.', 'Pfefferbaum, Betty', 'Vythilingam, Meena', 'Martin, Gregory J.', 'Schorr, John K.', 'Boudreaux, Angela S.', 'Spitznagel, Edward L.', 'Hong, Barry A.']",,,,
,PMC,Answers to Quiz Corner,,PMC2777301,,,,,,,,,
,PMC,Respiratory viruses in bronchiolitis and their link to recurrent wheezing and asthma,http://dx.doi.org/10.1016/j.cll.2009.07.011,PMC2810250,,,"Bronchiolitis is the leading cause of hospitalization for children age <1 year and these hospitalized children have an increased risk of developing childhood asthma. It remains unclear, however, which children with severe bronchiolitis (e.g., an episode requiring hospitalization) will develop recurrent wheezing and/or asthma. Although many environmental and genetic factors may play a role in the pathway from bronchiolitis to asthma, this review focuses on the viruses that have been linked to bronchiolitis and how these viruses may predict or contribute to future wheezing and asthma. The review also discusses vitamin D as an emerging risk factor for respiratory infections and wheezing.",,"['Mansbach, Jonathan M.', 'Camargo, Carlos A.']",,,,
,PMC,Dermatology: the last 30 years – a rollercoaster ride,http://dx.doi.org/10.7861/clinmedicine.9-6-588,PMC4952302,,,,,"Greaves, Malcolm W",,,,
,PMC,Acute Phase Response in Animals: A Review,,PMC2798837,,,"The acute phase response is a complex systemic early-defense system activated by trauma, infection, stress, neoplasia, and inflammation. Although nonspecific, it serves as a core of the innate immune response involving physical and molecular barriers and responses that serve to prevent infection, clear potential pathogens, initiate inflammatory processes, and contribute to resolution and the healing process. Acute phase proteins, an integral part of the acute phase response, have been a focus of many applications in human diagnostic medicine and recently have been identified in common animal species. Potential applications to diagnosis, prognosis, assessment of animal health, and laboratory animal welfare are readily apparent.",,"['Cray, Carolyn', 'Zaias, Julia', 'Altman, Norman H']",,,,
,PMC,RPS25 is essential for translation initiation by the Dicistroviridae and hepatitis C viral IRESs,http://dx.doi.org/10.1101/gad.1832209,PMC2788332,,,"Most eukaryotic mRNAs are translated using a cap-dependent mechanism of translation. However, ∼10% of mammalian mRNAs initiate translation using a cap-independent mechanism that is not well understood. These mRNAs contain an internal ribosome entry site (IRES) located in the 5′ untranslated region. The cricket paralysis virus (CrPV) intergenic region IRES (IGR IRES) functions in yeast, mammals, and plants, and does not require any translation initiation factors. We used yeast genetics to understand how ribosomes are recruited directly to the mRNA by an IRES. We found that Rps25p has an essential role in CrPV IGR IRES activity in yeast and mammalian cells but not in cap-dependent translation. Purified 40S ribosomal subunits lacking Rps25 are unable to bind to the IGR IRES in vitro. The hepatitis C virus (HCV) IRES also requires Rps25, demonstrating the function of Rps25 is conserved across IRES types. Yeast strains lacking Rps25 exhibit only slight defects in global translation, readthrough, ribosome biogenesis, and programmed ribosomal frameshifting. This work is the first demonstration of a ribosomal protein that is specifically required for IRES-mediated translation initiation. Our findings provide us with the beginnings of a model for the molecular interactions of an IRES with the ribosome.",,"['Landry, Dori M.', 'Hertz, Marla I.', 'Thompson, Sunnie R.']",,,,
,PMC,Heat shock proteins and superantigenic properties of bacteria from the gastrointestinal tract of patients with Kawasaki disease,http://dx.doi.org/10.1111/j.1365-2567.2009.03135.x,PMC2792135,,,"We previously suggested that gut bacteria may be involved in the onset of Kawasaki disease (KD). In this study, we evaluated the production of heat shock proteins (hsps) and superantigens (sAgs) by microorganisms isolated from the jejunal mucosa of 19 children with KD in the acute phase and from 15 age-matched control children. We identified 13 strains of Gram-negative microbes from patients with KD; these microbes produced large amounts of hsp60 and induced pro-inflammatory cytokine production by peripheral blood mononuclear cells. The Gram-negative microbes also elicited endogenous hsp60 production, leading to the secretion of anti-inflammatory intereukin-10 (IL-10). We also identified 18 strains of Gram-positive cocci that had superantigenic properties and which induced the expansion of Vβ2 T cells in vitro. All bacteria identified in this study were antibiotic resistant. These data suggest that sAg and hsps produced by gut bacteria might be involved in KD.",,"['Nagata, Satoru', 'Yamashiro, Yuichiro', 'Ohtsuka, Yoshikazu', 'Shimizu, Toshiaki', 'Sakurai, Yumiko', 'Misawa, Shigeki', 'Ito, Teruyo']",,,,
,PMC,The cytolytic molecules Fas ligand and TRAIL are required for murine thymic graft-versus-host disease,http://dx.doi.org/10.1172/JCI39395,PMC2798682,,,"Thymic graft-versus-host disease (tGVHD) can contribute to profound T cell deficiency and repertoire restriction after allogeneic BM transplantation (allo-BMT). However, the cellular mechanisms of tGVHD and interactions between donor alloreactive T cells and thymic tissues remain poorly defined. Using clinically relevant murine allo-BMT models, we show here that even minimal numbers of donor alloreactive T cells, which caused mild nonlethal systemic graft-versus-host disease, were sufficient to damage the thymus, delay T lineage reconstitution, and compromise donor peripheral T cell function. Furthermore, to mediate tGVHD, donor alloreactive T cells required trafficking molecules, including CCR9, L selectin, P selectin glycoprotein ligand-1, the integrin subunits α(E) and β(7), CCR2, and CXCR3, and costimulatory/inhibitory molecules, including Ox40 and carcinoembryonic antigen-associated cell adhesion molecule 1. We found that radiation in BMT conditioning regimens upregulated expression of the death receptors Fas and death receptor 5 (DR5) on thymic stromal cells (especially epithelium), while decreasing expression of the antiapoptotic regulator cellular caspase-8–like inhibitory protein. Donor alloreactive T cells used the cognate proteins FasL and TNF-related apoptosis-inducing ligand (TRAIL) (but not TNF or perforin) to mediate tGVHD, thereby damaging thymic stromal cells, cytoarchitecture, and function. Strategies that interfere with Fas/FasL and TRAIL/DR5 interactions may therefore represent a means to attenuate tGVHD and improve T cell reconstitution in allo-BMT recipients.",,"['Na, Il-Kang', 'Lu, Sydney X.', 'Yim, Nury L.', 'Goldberg, Gabrielle L.', 'Tsai, Jennifer', 'Rao, Uttam', 'Smith, Odette M.', 'King, Christopher G.', 'Suh, David', 'Hirschhorn-Cymerman, Daniel', 'Palomba, Lia', 'Penack, Olaf', 'Holland, Amanda M.', 'Jenq, Robert R.', 'Ghosh, Arnab', 'Tran, Hien', 'Merghoub, Taha', 'Liu, Chen', 'Sempowski, Gregory D.', 'Ventevogel, Melissa', 'Beauchemin, Nicole', 'van den Brink, Marcel R.M.']",,,,
,PMC,Rat respiratory coronavirus infection: replication in airway and alveolar epithelial cells and the innate immune response,http://dx.doi.org/10.1099/vir.0.014282-0,PMC2887555,,,"The rat coronavirus sialodacryoadenitis virus (SDAV) causes respiratory infection and provides a system for investigating respiratory coronaviruses in a natural host. A viral suspension in the form of a microspray aerosol was delivered by intratracheal instillation into the distal lung of 6–8-week-old Fischer 344 rats. SDAV inoculation produced a 7 % body weight loss over a 5 day period that was followed by recovery over the next 7 days. SDAV caused focal lesions in the lung, which were most severe on day 4 post-inoculation (p.i.). Immunofluorescent staining showed that four cell types supported SDAV virus replication in the lower respiratory tract, namely Clara cells, ciliated cells in the bronchial airway and alveolar type I and type II cells in the lung parenchyma. In bronchial alveolar lavage fluid (BALF) a neutrophil influx increased the population of neutrophils to 45 % compared with 6 % of the cells in control samples on day 2 after mock inoculation. Virus infection induced an increase in surfactant protein SP-D levels in BALF of infected rats on days 4 and 8 p.i. that subsided by day 12. The concentrations of chemokines MCP-1, LIX and CINC-1 in BALF increased on day 4 p.i., but returned to control levels by day 8. Intratracheal instillation of rats with SDAV coronavirus caused an acute, self-limited infection that is a useful model for studying the early events of the innate immune response to respiratory coronavirus infections in lungs of the natural virus host.",,"['Funk, C. Joel', 'Manzer, Rizwan', 'Miura, Tanya A.', 'Groshong, Steve D.', 'Ito, Yoko', 'Travanty, Emily A.', 'Leete, Jennifer', 'Holmes, Kathryn V.', 'Mason, Robert J.']",,,,
,PMC,Multiple novel astrovirus species in human stool,http://dx.doi.org/10.1099/vir.0.014449-0,PMC2796194,,,"Diarrhoea remains a significant cause of morbidity and mortality in developing countries where numerous cases remain without identified aetiology. Astroviruses are a recently identified cause of animal gastroenteritis which currently includes two species suspected of causing human diarrhoea. Using pan-astrovirus RT-PCR, we analysed human stool samples from different continents for astrovirus-related RNA sequences. We identified variants of the two known human astrovirus species plus, based on genetic distance criteria, three novel astrovirus species all distantly related to mink and ovine astroviruses, which we provisionally named HMOAstV species A–C. The complete genome of species A displayed all the conserved characteristics of mammalian astroviruses. Each of the now three groups of astroviruses found in human stool (HAstV, AstV-MLB and HMOAstV) were more closely related to animal astroviruses than to each other, indicating that human astroviruses may periodically emerge from zoonotic transmissions. Based on the pathogenic impact of their closest phylogenetic relatives in animals, further investigations of the role of HMOAstV, so far detected in Nigeria, Nepal and Pakistan, in human gastroenteritis are warranted.",,"['Kapoor, A.', 'Li, L.', 'Victoria, J.', 'Oderinde, B.', 'Mason, C.', 'Pandey, P.', 'Zaidi, S. Z.', 'Delwart, E.']",,,,
,PMC,Synthetic viruses: a new opportunity to understand and prevent viral disease,http://dx.doi.org/10.1038/nbt.1593,PMC2819212,,,"Rapid progress in DNA synthesis and sequencing is spearheading the deliberate, large-scale genetic alteration of organisms. These new advances in DNA manipulation have been extended to the level of whole-genome synthesis, as evident from the synthesis of poliovirus, from the resurrection of the extinct 1918 strain of influenza virus and of human endogenous retroviruses and from the restructuring of the phage T7 genome. The largest DNA synthesized so far is the 582,970 base pair genome of Mycoplasma genitalium, although, as yet, this synthetic DNA has not been ‘booted’ to life. As genome synthesis is independent of a natural template, it allows modification of the structure and function of a virus’s genetic information to an extent that was hitherto impossible. The common goal of this new strategy is to further our understanding of an organism’s properties, particularly its pathogenic armory if it causes disease in humans, and to make use of this new information to protect from, or treat, human viral disease. Although only a few applications of virus synthesis have been described as yet, key recent findings have been the resurrection of the 1918 influenza virus and the generation of codon- and codon pair–deoptimized polioviruses.",,"['Wimmer, Eckard', 'Mueller, Steffen', 'Tumpey, Terrence M', 'Taubenberger, Jeffery K']",,,,
,PMC,Genetic basis for variation of vaccine response: our studies with rubella vaccine,http://dx.doi.org/10.1016/j.paed.2009.08.019,PMC2957833,,,"Congenital rubella syndrome still occurs throughout the world despite an effective vaccine being used in developed countries. Heat and light lability, as well as contraindications in immunocompromised persons, limit the use of the vaccine. An improved, more durable and less reactive rubella vaccine such as a peptide or subunit vaccine would address these unmet needs. We have sought to identify the genetic factors that influence both humoral and cell-mediated immunity. Specifically, we have examined genetic polymorphisms and their associations with variations in the immune response to rubella vaccine. Our previous work with twins has identified substantial heritability with rubella vaccine antibody response. We have since identified human leukocyte antigen associations, with both humoral (class II) and cellular (class I) immunity. Our preliminary work with genetic determinants in cytokines and their receptors have offered tantalising leads as well. Now, having recruited a larger cohort to combine with our previous sample, we lay out in this paper our specific aims for a larger, more comprehensive study of the genetic associations with rubella vaccine response and components of both humoral and cellular immunity.",,"['Jacobson, Robert M.', 'Ovsyannikova, Inna G.', 'Poland, Gregory A.']",,,,
,PMC,Challenging a Paradigm: Theoretical Calculations of the Protonation State of the Cys25-His159 Catalytic Diad in Free Papain,http://dx.doi.org/10.1002/prot.22516,PMC2767454,,,"A central mechanistic paradigm of cysteine proteases is that the His – Cys catalytic diad forms an ion-pair NH(+)/S(−) already in the catalytically active free enzyme. Most molecular modeling studies of cysteine proteases refer to this paradigm as their starting point. Nevertheless, several recent kinetics and X-ray crystallography studies of viral and bacterial cysteine proteases depart from the ion-pair mechanism, suggesting general base catalysis. We challenge the postulate of the ion-pair formation in free papain. Applying our QM/SCRF(VS) molecular modeling approach, we analyzed all protonation states of the catalytic diad in free papain and its SMe derivative, comparing the predicted and experimental pK(a) data. We conclude that the His – Cys catalytic diad in free papain is fully protonated, NH(+)/SH. The experimental pK(a)=8.62 of His159 imidazole in free papain, obtained by NMR controlled titratin and originally interpreated as the NH(+)/S(−) ⇌ N/S(−) equilibrium, is now assigned to the NH(+)/SH ⇌ N/SH equilibrium.",,"['Shokhen, Michael', 'Khazanov, Netaly', 'Albeck, Amnon']",,,,
,PMC,Central Neuroinvasion and Demyelination by Inflammatory Macrophages After Peripheral Virus Infection is Controlled by SHP-1,http://dx.doi.org/10.1089/vim.2009.0052,PMC2883524,,,"SHP-1 is a protein tyrosine phosphatase that negatively regulates cytokine signaling and inflammatory gene expression. Mice genetically lacking SHP-1 (me/me) display severe inflammatory demyelinating disease following intracranial inoculation with the BeAn strain of Theiler's murine encephalomyelitis virus (TMEV) compared to infected wild-type mice. Furthermore, SHP-1-deficient mice show a profound and predominant infiltration of blood-derived macrophages into the CNS following intracerebral injection of TMEV, and these macrophages are concentrated in areas of demyelination in brain and spinal cord. In the present study we investigated the role of SHP-1 in controlling CNS inflammatory demyelination following a peripheral instead of an intracerebral inoculation of TMEV. Surprisingly, we found that while wild-type mice were entirely refractory to intraperitoneal (IP) infection by TMEV, in agreement with previous studies, all SHP-1-deficient mice displayed profound macrophage neuroinvasion and macrophage-mediated inflammatory demyelination. Moreover, SHP-1 deficiency led to increased expression of inflammatory molecules in macrophages, serum, and CNS following IP infection with TMEV. Importantly, pharmacological depletion of peripheral macrophages significantly decreased both paralysis and CNS viral loads in SHP-1-deficient mice. In addition, peripheral MCP-1 neutralization attenuated disease severity, decreased macrophage infiltration into the CNS, and decreased monocyte numbers in the blood of SHP-1-deficient mice, implicating MCP-1 as an important mediator of monocyte migration between multiple tissues. These results demonstrate that peripheral TMEV infection results in a unique evolution of macrophage-mediated demyelination in SHP-1-deficient mice, implicating SHP-1 in the control of neuroinvasion of inflammatory macrophages and neurotropic viruses into the CNS.",,"['Christophi, George P.', 'Massa, Paul T.']",,,,
,PMC,Principles and Practice of Clinical Virology,http://dx.doi.org/10.1089/vim.2009.0073,PMC2883518,,,,,,,,,
,PMC,Targeting the Degradation of Angiotensin II with Recombinant ACE2: Prevention of Angiotensin II-dependent Hypertension,http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.138420,PMC2827767,,,"Angiotensin converting enzyme 2 (ACE2) cleaves angiotensin II (Ang II) to form Ang-(1-7). Here we examined whether soluble human recombinant ACE2 (rACE2) can efficiently lower Ang II and increase Ang-(1-7), and whether rACE2 can prevent hypertension caused by Ang II infusion as a result of systemic versus local mechanisms of ACE2 activity amplification. rACE2 was infused via osmotic minipumps for three days in conscious mice or acutely in anesthetized mice. rACE2 caused a dose-dependent increase in serum ACE2 activity but had no effect on kidney or cardiac ACE2 activity. Following Ang II infusion (40pmol/min), rACE2 (1mg/kg/d) resulted in normalization of systolic blood pressure and plasma Ang II. In acute studies, rACE2 (1mg/kg) prevented the rapid hypertensive effect of Ang II (0.2mg/kg), and this was associated with both a decrease in Ang II and an increase in Ang-(1-7) in plasma. Moreover, during infusion of Ang II, the effect of rACE2 on blood pressure was unaffected by a specific Ang-(1-7) receptor blocker, A779 (0.2 mg/kg), and infusing supra-physiologic levels of Ang-(1-7) (0.2 mg/kg) had no effect on blood pressure. We conclude that during Ang II infusion rACE2 effectively degrades Ang II and in the process normalizes blood pressure. The mechanism of rACE2 action results from an increase in systemic, not tissue, ACE2 activity and the lowering of plasma Ang II rather than the attendant increase in Ang-(1-7). Increasing ACE2 activity may provide a new therapeutic target in states of Ang II over-activity by enhancing its degradation, an approach that differs from the current focus on blocking Ang II formation and action.",,"['Wysocki, Jan', 'Ye, Minghao', 'Rodriguez, Eva', 'González-Pacheco, Francisco R.', 'Barrios, Clara', 'Evora, Karla', 'Schuster, Manfred', 'Loibner, Hans', 'Brosnihan, K. Bridget', 'Ferrario, Carlos M.', 'Penninger, Josef M.', 'Batlle, Daniel']",,,,
,PMC,HIV and tuberculosis in Russia and eastern Europe: sounding the alarm,http://dx.doi.org/10.1097/QAD.0b013e328332d5f8,PMC5523929,,,,,"['Vorkas, Charles Kyriakos', 'van der Horst, Charles']",,,,
,PMC,A robust lentiviral pseudotype neutralisation assay for in-field serosurveillance of rabies and lyssaviruses in Africa,http://dx.doi.org/10.1016/j.vaccine.2009.09.024,PMC2789314,19925950,CC BY,"The inflexibility of existing serological techniques for detection of rabies in surveillance constrains the benefit to be gained from many current control strategies. We analysed 304 serum samples from Tanzanian dogs for the detection of rabies antibodies in a pseudotype assay using lentiviral vectors bearing the CVS-11 envelope glycoprotein. Compared with the widely used gold standard fluorescent antibody virus neutralisation assay, a specificity of 100% and sensitivity of 94.4% with a strong correlation of antibody titres (r = 0.915) were observed with the pseudotype assay. To increase the assay's surveillance specificity in Africa we incorporated the envelope glycoprotein of local viruses, Lagos bat virus, Duvenhage virus or Mokola virus and also cloned the lacZ gene to provide a reporter element. Neutralisation assays using pseudotypes bearing these glycoproteins reveal that they provide a greater sensitivity compared to similar live virus assays and will therefore allow a more accurate determination of the distribution of these highly pathogenic infections and the threat they pose to human health. Importantly, the CVS-11 pseudotypes were highly stable during freeze–thaw cycles and storage at room temperature. These results suggest the proposed pseudotype assay is a suitable option for undertaking lyssavirus serosurveillance in areas most affected by these infections.",2009 Nov 27,"['Wright, Edward', 'McNabb, Suzanne', 'Goddard, Trudy', 'Horton, Daniel L.', 'Lembo, Tiziana', 'Nel, Louis H.', 'Weiss, Robin A.', 'Cleaveland, Sarah', 'Fooks, Anthony R.']",Vaccine,,,
,PMC,Assessment of intervention strategies against a novel influenza epidemic using an individual-based model,http://dx.doi.org/10.1007/s12199-009-0122-9,PMC2854337,,,"OBJECTIVES: The objective of this study was to assess intervention strategies against a novel influenza epidemic through simulations of various scenarios in Sapporo city, Hokkaido, Japan. A series of interventions were examined: administration of antiviral drugs by two approaches [targeted antiviral prophylaxis (TAP) and school-age targeted antiviral prophylaxis (STAP)], school closure, restraint, and combinations of these four interventions. METHODS: In order to generate a more realistic situation, we constructed an individual-based model (IBM) for the transmission of influenza in which each individual was assigned personal information on the basis of the National Census and Employment Status Survey of Sapporo city. In addition, data on high-risk casual contact groups commuting in crowded trains and buses were obtained from a census on transportation modes and introduced into the model. Observational data from previous pandemics were used for the epidemiological parameters. RESULTS: Both TAP and STAP interventions were highly effective in suppressing the spread of infection during the early period of an outbreak, but STAP was inferior to TAP in terms of the ripple effect of the administration of antiviral drugs. School closure and restraint were able to bring about a delay in the peak of infection. The combination of TAP, school closure, and restraint interventions were highly effective in decreasing the total number of patients and shortening the epidemic period. CONCLUSIONS: Based on the simulation results, we recommend implementing TAP together with both school closure and restraint as strategies against a future novel influenza outbreak.",,"['Morimoto, Tomoko', 'Ishikawa, Hirofumi']",,,,
,PMC,The Minor Envelope Glycoproteins GP2a and GP4 of Porcine Reproductive and Respiratory Syndrome Virus Interact with the Receptor CD163,http://dx.doi.org/10.1128/JVI.01774-09,PMC2812361,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) contains the major glycoprotein, GP5, as well as three other minor glycoproteins, namely, GP2a, GP3, and GP4, on the virion envelope, all of which are required for generation of infectious virions. To study their interactions with each other and with the cellular receptor for PRRSV, we have cloned each of the viral glycoproteins and CD163 receptor in expression vectors and examined their expression and interaction with each other in transfected cells by coimmunoprecipitation (co-IP) assay using monospecific antibodies. Our results show that a strong interaction exists between the GP4 and GP5 proteins, although weak interactions among the other minor envelope glycoproteins and GP5 have been detected. Both GP2a and GP4 proteins were found to interact with all the other GPs, resulting in the formation of multiprotein complex. Our results further show that the GP2a and GP4 proteins also specifically interact with the CD163 molecule. The carboxy-terminal 223 residues of the CD163 molecule are not required for interactions with either the GP2a or the GP4 protein, although these residues are required for conferring susceptibility to PRRSV infection in BHK-21 cells. Overall, we conclude that the GP4 protein is critical for mediating interglycoprotein interactions and, along with GP2a, serves as the viral attachment protein that is responsible for mediating interactions with CD163 for virus entry into susceptible host cell.",,"['Das, Phani B.', 'Dinh, Phat X.', 'Ansari, Israrul H.', 'de Lima, Marcelo', 'Osorio, Fernando A.', 'Pattnaik, Asit K.']",,,,
,PMC,A Replication-incompetent Rift Valley Fever Vaccine: Chimeric Virus-like Particles Protect Mice and Rats Against Lethal Challenge,http://dx.doi.org/10.1016/j.virol.2009.11.001,PMC2813982,,,"Virus-like particles (VLPs) present viral antigens in a native conformation and are effectively recognized by the immune system and therefore are considered as suitable and safe vaccine candidates against many viral diseases. Here we demonstrate that chimeric VLPs containing Rift Valley fever virus (RVFV) glycoproteins G(N) and G(C), nucleoprotein N and the gag protein of Moloney murine leukemia virus represent an effective vaccine candidate against Rift Valley fever, a deadly disease in humans and livestock. Long-lasting humoral and cellular immune responses are demonstrated in a mouse model by the analysis of neutralizing antibody titers and cytokine secretion profiles. Vaccine efficacy studies were performed in mouse and rat lethal challenge models resulting in high protection rates. Taken together, these results demonstrate that replication-incompetent chimeric RVF VLPs are an efficient RVFV vaccine candidate.",,"['Mandell, Robert B.', 'Koukuntla, Ramesh', 'Mogler, Laura J. K.', 'Carzoli, Andrea K.', 'Freiberg, Alexander N.', 'Holbrook, Michael R.', 'Martin, Brian K.', 'Staplin, William R.', 'Vahanian, Nicholas N.', 'Link, Charles J.', 'Flick, Ramon']",,,,
,PMC,Influenza—Insights from Mathematical Modelling,http://dx.doi.org/10.3238/arztebl.2009.0777,PMC2795334,,,"BACKGROUND: When the first cases of a new infectious disease appear, questions arise about the further course of the epidemic and about the appropriate interventions to be taken to protect individuals and the public as a whole. Mathematical models can help answer these questions. In this article, the authors describe basic concepts in the mathematical modelling of infectious diseases, illustrate their use with a simple example, and present the results of influenza models. METHOD: Description of the mathematical modelling of infectious diseases and selective review of the literature. RESULTS: The two fundamental concepts of mathematical modelling of infectious diseases—the basic reproduction number and the generation time—allow a better understanding of the course of an epidemic. Modelling studies based on past influenza epidemics suggest that the rise of the epidemic curve can be slowed at the beginning of the epidemic by isolating ill persons and giving prophylactic medications to their contacts. Later on in the course of the epidemic, restricting the number of contacts (e.g., by closing schools) may mitigate the epidemic but will only have a limited effect on the total number of persons who contract the disease. CONCLUSION: Mathematical modelling is a valuable tool for understanding the dynamics of an epidemic and for planning and evaluating interventions.",,"['Mikolajczyk, Rafael', 'Krumkamp, Ralf', 'Bornemann, Reinhard', 'Ahmad, Amena', 'Schwehm, Markus', 'Duerr, Hans-Peter']",,,,
,PMC,The economy-wide impact of pandemic influenza on the UK: a computable general equilibrium modelling experiment,http://dx.doi.org/10.1136/bmj.b4571,PMC2779854,19926697,CC BY-NC,"Objectives To estimate the potential economic impact of pandemic influenza, associated behavioural responses, school closures, and vaccination on the United Kingdom. Design A computable general equilibrium model of the UK economy was specified for various combinations of mortality and morbidity from pandemic influenza, vaccine efficacy, school closures, and prophylactic absenteeism using published data. Setting The 2004 UK economy (the most up to date available with suitable economic data). Main outcome measures The economic impact of various scenarios with different pandemic severity, vaccination, school closure, and prophylactic absenteeism specified in terms of gross domestic product, output from different economic sectors, and equivalent variation. Results The costs related to illness alone ranged between 0.5% and 1.0% of gross domestic product (£8.4bn to £16.8bn) for low fatality scenarios, 3.3% and 4.3% (£55.5bn to £72.3bn) for high fatality scenarios, and larger still for an extreme pandemic. School closure increases the economic impact, particularly for mild pandemics. If widespread behavioural change takes place and there is large scale prophylactic absence from work, the economic impact would be notably increased with few health benefits. Vaccination with a pre-pandemic vaccine could save 0.13% to 2.3% of gross domestic product (£2.2bn to £38.6bn); a single dose of a matched vaccine could save 0.3% to 4.3% (£5.0bn to £72.3bn); and two doses of a matched vaccine could limit the overall economic impact to about 1% of gross domestic product for all disease scenarios. Conclusion Balancing school closure against “business as usual” and obtaining sufficient stocks of effective vaccine are more important factors in determining the economic impact of an influenza pandemic than is the disease itself. Prophylactic absence from work in response to fear of infection can add considerably to the economic impact.",2009 Nov 19,"['Smith, Richard D', 'Keogh-Brown, Marcus R', 'Barnett, Tony', 'Tait, Joyce']",BMJ,,,
,PMC,Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 1β Modulates Host Innate Immune Response by Antagonizing IRF3 Activation,http://dx.doi.org/10.1128/JVI.01326-09,PMC2812326,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) infection of swine leads to a serious disease characterized by a delayed and defective adaptive immune response. It is hypothesized that a suboptimal innate immune response is responsible for the disease pathogenesis. In the study presented here we tested this hypothesis and identified several nonstructural proteins (NSPs) with innate immune evasion properties encoded by the PRRS viral genome. Four of the total ten PRRSV NSPs tested were found to have strong to moderate inhibitory effects on beta interferon (IFN-β) promoter activation. The strongest inhibitory effect was exhibited by NSP1 followed by, NSP2, NSP11, and NSP4. We focused on NSP1α and NSP1β (self-cleavage products of NSP1 during virus infection) and NSP11, three NSPs with strong inhibitory activity. All of three proteins, when expressed stably in cell lines, strongly inhibited double-stranded RNA (dsRNA) signaling pathways. NSP1β was found to inhibit both IFN regulatory factor 3 (IRF3)- and NF-κB-dependent gene induction by dsRNA and Sendai virus. Mechanistically, the dsRNA-induced phosphorylation and nuclear translocation of IRF3 were strongly inhibited by NSP1β. Moreover, when tested in a porcine myelomonocytic cell line, NSP1β inhibited Sendai virus-mediated activation of porcine IFN-β promoter activity. We propose that this NSP1β-mediated subversion of the host innate immune response plays an important role in PRRSV pathogenesis.",,"['Beura, Lalit K.', 'Sarkar, Saumendra N.', 'Kwon, Byungjoon', 'Subramaniam, Sakthivel', 'Jones, Clinton', 'Pattnaik, Asit K.', 'Osorio, Fernando A.']",,,,
,PMC,Elevated Temperature Triggers Human Respiratory Syncytial Virus F Protein Six-Helix Bundle Formation,http://dx.doi.org/10.1016/j.virol.2009.10.040,PMC2789909,,,"Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infection in infants, immunocompromised patients, and the elderly. The RSV fusion (F) protein mediates fusion of the viral envelope with the target cell membrane during virus entry and is a primary target for antiviral drug and vaccine development. The F protein contains two heptad repeat regions, HR1 and HR2. Peptides corresponding to these regions form a six-helix bundle structure that is thought to play a critical role in membrane fusion. However, characterization of six-helix bundle formation in native RSV F protein has been hindered by the fact that a trigger for F protein conformational change has yet to be identified. Here we demonstrate that RSV F protein on the surface of infected cells undergoes a conformational change following exposure to elevated temperature, resulting in the formation of the six-helix bundle structure. We first generated and characterized six-helix-bundle-specific antibodies raised against recombinant peptides modeling the RSV F protein six-helix bundle structure. We then used these antibodies as probes to monitor RSV F protein six-helix bundle formation in response to a diverse array of potential triggers of conformational changes. We found that exposure of ‘membrane-anchored’ RSV F protein to elevated temperature (45-55°C) was sufficient to trigger six-helix bundle formation. Antibody binding to the six-helix bundle conformation was detected by both flow cytometry and cell-surface immunoprecipitation of the RSV F protein. None of the other treatments, including interaction with a number of potential receptors, resulted in significant binding by six-helix bundle-specific antibodies. We conclude that native, untriggered RSV F protein exists in a metastable state that can be converted in vitro to the more stable, fusogenic six-helix bundle conformation by an increase in thermal energy. These findings help to better define the mechanism of RSV F-mediated membrane fusion and have important implications for the identification of therapeutic strategies and vaccines targeting RSV F protein conformational changes.",,"['Yunus, Abdul S.', 'Jackson, Trent P.', 'Crisafi, Katherine', 'Burimski, Irina', 'Kilgore, Nicole R.', 'Zoumplis, Dorian', 'Allaway, Graham P.', 'Wild, Carl T.', 'Salzwedel, Karl']",,,,
,PMC,"Cellular Pharmacology of the Anti-Hepatitis B Virus Agent β-l-2′,3′-Didehydro-2′,3′-Dideoxy-N(4)-Hydroxycytidine: Relevance for Activation in HepG2 Cells",http://dx.doi.org/10.1128/AAC.01176-09,PMC2798482,,,"ß-l-2′,3′-Didehydro-2′,3′-dideoxy-N(4)-hydroxycytidine (l-Hyd4C) was demonstrated to be an effective and highly selective inhibitor of hepatitis B virus (HBV) replication in HepG2.2.15 cells (50% effective dose [ED(50)] = 0.03 μM; 50% cytotoxic dose [CD(50)] = 2,500 μM). In the present study, we investigated the intracellular pharmacology of tritiated l-Hyd4C in HepG2 cells. l-[(3)H]Hyd4C was shown to be phosphorylated extensively and rapidly to the 5′-mono-, 5′-di-, and 5′-triphosphate derivatives. Other metabolites deriving from a reduction or removal of the NHOH group of l-Hyd4C could not be detected, although both reactions were described as the primary catabolic pathways of the stereoisomer ß-d-N(4)-hydroxycytidine in HepG2 cells. Also, the formation of liponucleotide metabolites, such as the 5′-diphosphocholine derivative of l-Hyd4C, as described for some l-deoxycytidine analogues, seems to be unlikely. After incubation of HepG2 cells with 10 μM l-[(3)H]Hyd4C for 24 h, the 5′-triphosphate accumulated to 19.4 ± 2.7 pmol/10(6) cells. The predominant peak belonged to 5-diphosphate, with 43.5 ± 4.3 pmol/10(6) cells. The intracellular half-life of the 5′-triphosphate was estimated to be 29.7 h. This extended half-life probably reflects a generally low affinity of 5′-phosphorylated l-deoxycytidine derivatives for phosphate-degrading enzymes but may additionally be caused by an efficient rephosphorylation of the 5′-diphosphate during a drug-free incubation. The high 5′-triphosphate level and its extended half-life in HepG2 cells are consistent with the potent antiviral activity of l-Hyd4C.",,"['Matthes, E.', 'Bünger, H.']",,,,
,PMC,Social Network Analyses of Patient-Healthcare Worker Interactions: Implications for Disease Transmission,,PMC2815400,,,"Patients and healthcare workers (HCW) in healthcare settings represent a unique social network in which the risk of transmission of an infection is considered to be higher for both HCW and patients. Using data from existing clinical informatics resources, we constructed social networks of patient-HCW interactions in the emergency department of a tertiary care pediatric hospital. The structural properties of these networks were analyzed and compared to other well known networks. Patient-HCW networks do not demonstrate the classical power-law distribution of scale-free networks, thus indicating that they are different from social networks of individuals in a community. The clustering coefficient is larger as compared to a random network, indicating small world properties. The eigenvector centrality, used to identify the most important nodes, reveals HCW to be more connected than patients. These properties imply differences that must be taken into account when analyzing patient-HCW networks and planning interventions and mitigation strategies to prevent the spread of infectious diseases in healthcare settings.",,"['Gundlapalli, Adi', 'Ma, Xiulian', 'Benuzillo, Jose', 'Pettey, Warren', 'Greenberg, Richard', 'Hales, Joseph', 'Leecaster, Molly', 'Samore, Matthew']",,,,
,PMC,A non-adjuvanted polypeptide nanoparticle vaccine confers long-lasting protection against rodent malaria(),http://dx.doi.org/10.4049/jimmunol.0901957,PMC4528972,,,"We have designed and produced a prototypic malaria vaccine based on a highly versatile self-assembling polypeptide nanoparticle (SAPN) platform that can repetitively display antigenic epitopes. We used this platform to display a tandem repeat of the B cell immunodominant repeat epitope (DPPPPNPN)(2)D of the malaria parasite Plasmodium berghei circumsporozoite protein (CSP). Administered in saline, without the need for a heterologous adjuvant, the SAPN construct P4c-Mal conferred a long lived protective immune response to mice with a broad range of genetically distinct immune backgrounds including the H-2(b), H-2(d) and H-2(k) alleles. Immunized mice produced a CD4(+) T cell dependent, high titer, long lasting, high avidity antibody response against the B cell epitope. Mice were protected against an initial challenge of parasites given up to 6 months after the last immunization or for up to 15 months against a second challenge after an initial challenge of parasites had successfully been cleared. Furthermore, we demonstrate that the SAPN platform not only functions to deliver an ordered repetitive array of B cell peptide epitopes but operates as a classical immunological carrier to provide cognate help to the P4c-Mal specific B cells.",,"['Abanega Kaba, Stephen', 'Brando, Clara', 'Guo, Qin', 'Mittelholzer, Christian', 'Raman, Senthilkumar', 'Tropel, David', 'Aebi, Ueli', 'Burkhard, Peter', 'Ervin Lanar, David']",,,,
,PMC,The early diversification of influenza A/H1N1pdm,http://dx.doi.org/10.1371/currents.RRN1126,PMC2773564,20029664,CC BY,"Background Since its initial detection in April 2009, the A/H1N1pdm influenza virus has spread rapidly in humans, with over 5,700 human deaths. However, little is known about the evolutionary dynamics of H1N1pdm and its geographic and temporal diversification. Methods Phylogenetic analysis was conducted upon the concatenated coding regions of whole-genome sequences from 290 H1N1pdm isolates sampled globally between April 1 – July 9, 2009, including relatively large samples from the US states of Wisconsin and New York. Results At least 7 phylogenetically distinct viral clades have disseminated globally and co-circulated in localities that experienced multiple introductions of H1N1pdm. The epidemics in New York and Wisconsin were dominated by two different clades, both phylogenetically distinct from the viruses first identified in California and Mexico, suggesting an important role for founder effects in determining local viral population structures. Conclusions Determining the global diversity of H1N1pdm is central to understanding the evolution and spatial spread of the current pandemic, and to predict its future impact on human populations. Our results indicate that H1N1pdm has already diversified into distinct viral lineages with defined spatial patterns.",2009 Nov 12,"['Nelson, Martha', 'Spiro, David', 'Wentworth, David', 'Fan, Jiang', 'Beck, Eric', 'St. George, Kirsten', 'Ghedin, Elodie', 'Halpin, Rebecca', 'Bera, Jayati', 'Hine, Erin', 'Proudfoot, Kathleen', 'Stockwell, Tim', 'Lin, Xudong', 'Griesemer, Sara', 'Bose, Michael', 'Jurgens, Lisa', 'Kumar, Swati', 'Viboud, Cecile', 'Holmes, Edward', 'Henrickson, Kelly']",PLoS Curr,,,
,PMC,"Recombination, Reservoirs, and the Modular Spike: Mechanisms of Coronavirus Cross-Species Transmission",http://dx.doi.org/10.1128/JVI.01394-09,PMC2838128,,,"Over the past 30 years, several cross-species transmission events, as well as changes in virus tropism, have mediated significant animal and human diseases. Most notable is severe acute respiratory syndrome (SARS), a lower respiratory tract disease of humans that was first reported in late 2002 in Guangdong Province, China. The disease, which quickly spread worldwide over a period of 4 months spanning late 2002 and early 2003, infected over 8,000 individuals and killed nearly 800 before it was successfully contained by aggressive public health intervention strategies. A coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and initial assessments determined that the virus crossed to human hosts from zoonotic reservoirs, including bats, Himalayan palm civets (Paguma larvata), and raccoon dogs (Nyctereutes procyonoides), sold in exotic animal markets in Guangdong Province. In this review, we discuss the molecular mechanisms that govern coronavirus cross-species transmission both in vitro and in vivo, using the emergence of SARS-CoV as a model. We pay particular attention to how changes in the Spike attachment protein, both within and outside of the receptor binding domain, mediate the emergence of coronaviruses in new host populations.",,"['Graham, Rachel L.', 'Baric, Ralph S.']",,,,
,PMC,Cellular Immune Responses to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection in Senescent BALB/c Mice: CD4(+) T Cells Are Important in Control of SARS-CoV Infection,http://dx.doi.org/10.1128/JVI.01281-09,PMC2812346,,,"We characterized the cellular immune response to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in 12- to 14-month-old BALB/c mice, a model that mimics features of the human disease. Following intranasal administration, the virus replicated in the lungs, with peak titers on day 2 postinfection. Enhanced production of cytokines (tumor necrosis factor alpha [TNF-α] and interleukin-6 [IL-6]) and chemokines (CXCL10, CCL2, CCL3, and CCL5) correlated with migration of NK cells, macrophages, and plasmacytoid dendritic cells (pDC) into the lungs. By day 7, histopathologic evidence of pneumonitis was seen in the lungs when viral clearance occurred. At this time, a second wave of enhanced production of cytokines (TNF-α, IL-6, gamma interferon [IFN-γ], IL-2, and IL-5), chemokines (CXCL9, CXCL10, CCL2, CCL3, and CCL5), and receptors (CXCR3, CCR2, and CCR5), was detected in the lungs, associated with an influx of T lymphocytes. Depletion of CD8(+) T cells at the time of infection did not affect viral replication or clearance. However, depletion of CD4(+) T cells resulted in an enhanced immune-mediated interstitial pneumonitis and delayed clearance of SARS-CoV from the lungs, which was associated with reduced neutralizing antibody and cytokine production and reduced pulmonary recruitment of lymphocytes. Innate defense mechanisms are able to control SARS-CoV infection in the absence of CD4(+) and CD8(+) T cells and antibodies. Our findings provide new insights into the pathogenesis of SARS, demonstrating the important role of CD4(+) but not CD8(+) T cells in primary SARS-CoV infection in this model.",,"['Chen, Jun', 'Lau, Yuk Fai', 'Lamirande, Elaine W.', 'Paddock, Christopher D.', 'Bartlett, Jeanine H.', 'Zaki, Sherif R.', 'Subbarao, Kanta']",,,,
,PMC,Chimeric Feline Coronaviruses That Encode Type II Spike Protein on Type I Genetic Background Display Accelerated Viral Growth and Altered Receptor Usage,http://dx.doi.org/10.1128/JVI.01568-09,PMC2812337,,,"Persistent infection of domestic cats with feline coronaviruses (FCoVs) can lead to a highly lethal, immunopathological disease termed feline infectious peritonitis (FIP). Interestingly, there are two serotypes, type I and type II FCoVs, that can cause both persistent infection and FIP, even though their main determinant of host cell tropism, the spike (S) protein, is of different phylogeny and displays limited sequence identity. In cell culture, however, there are apparent differences. Type II FCoVs can be propagated to high titers by employing feline aminopeptidase N (fAPN) as a cellular receptor, whereas the propagation of type I FCoVs is usually difficult, and the involvement of fAPN as a receptor is controversial. In this study we have analyzed the phenotypes of recombinant FCoVs that are based on the genetic background of type I FCoV strain Black but encode the type II FCoV strain 79-1146 S protein. Our data demonstrate that recombinant FCoVs expressing a type II FCoV S protein acquire the ability to efficiently use fAPN for host cell entry and corroborate the notion that type I FCoVs use another main host cell receptor. We also observed that recombinant FCoVs display a large-plaque phenotype and, unexpectedly, accelerated growth kinetics indistinguishable from that of type II FCoV strain 79-1146. Thus, the main phenotypic differences for type I and type II FCoVs in cell culture, namely, the growth kinetics and the efficient usage of fAPN as a cellular receptor, can be attributed solely to the FCoV S protein.",,"['Tekes, Gergely', 'Hofmann-Lehmann, Regina', 'Bank-Wolf, Barbara', 'Maier, Reinhard', 'Thiel, Heinz-Jürgen', 'Thiel, Volker']",,,,
,PMC,Should noninvasive ventilation be considered a high-risk procedure during an epidemic?,http://dx.doi.org/10.1503/cmaj.081987,PMC2774359,,,,,"McCracken, John",,,,
,PMC,Highlights,,PMC2774357,,,,,,,,,
,PMC,Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor,http://dx.doi.org/10.1073/pnas.0908837106,PMC2785276,,,"NL63 coronavirus (NL63-CoV), a prevalent human respiratory virus, is the only group I coronavirus known to use angiotensin-converting enzyme 2 (ACE2) as its receptor. Incidentally, ACE2 is also used by group II SARS coronavirus (SARS-CoV). We investigated how different groups of coronaviruses recognize the same receptor, whereas homologous group I coronaviruses recognize different receptors. We determined the crystal structure of NL63-CoV spike protein receptor-binding domain (RBD) complexed with human ACE2. NL63-CoV RBD has a novel β-sandwich core structure consisting of 2 layers of β-sheets, presenting 3 discontinuous receptor-binding motifs (RBMs) to bind ACE2. NL63-CoV and SARS-CoV have no structural homology in RBD cores or RBMs; yet the 2 viruses recognize common ACE2 regions, largely because of a “virus-binding hotspot” on ACE2. Among group I coronaviruses, RBD cores are conserved but RBMs are variable, explaining how these viruses recognize different receptors. These results provide a structural basis for understanding viral evolution and virus–receptor interactions.",,"['Wu, Kailang', 'Li, Weikai', 'Peng, Guiqing', 'Li, Fang']",,,,
,PMC,"Improved health and survival of FIV-infected cats is associated with the presence of autoantibodies to the primary receptor, CD134",http://dx.doi.org/10.1073/pnas.0911307106,PMC2775039,,,"We analyzed antibody responses in sera from feline immunodeficiency virus (FIV)-infected and uninfected cats. A strong antiviral response to the viral surface glycoprotein (SU) was noted in both natural and experimental infections. In addition, 143 of 226 FIV-infected animals (63%) also expressed antibodies to the primary binding receptor, CD134, whereas cats infected with other feline RNA viruses, including calicivirus, coronavirus, herpesvirus, and feline leukemia virus, did not. Both affinity-purified anti-CD134 and anti-SU antibodies blocked FIV infection ex vivo. FACS analyses revealed that the anti-CD134 antibodies bound to a cryptic epitope on the receptor that was only exposed when SU bound to CD134. Anti-CD134 binding caused displacement of SU from the surface of the cell and inhibition of infection. The presence of antibodies to CD134 correlated with lower virus loads and a better overall health status in FIV(+) cats, whereas anti-SU antibodies were present independent of health status. The findings are consistent with a role for antireceptor antibodies in protection from virus spread and disease progression.",,"['Grant, Chris K.', 'Fink, Elizabeth A.', 'Sundstrom, Magnus', 'Torbett, Bruce E.', 'Elder, John H.']",,,,
,PMC,Reovirus nonstructural protein σ1s is required for establishment of viremia and systemic dissemination,http://dx.doi.org/10.1073/pnas.0907412106,PMC2774258,,,"Serotype-specific patterns of reovirus disease in the CNS of newborn mice segregate with the viral S1 gene segment, which encodes attachment protein σ1 and nonstructural protein σ1s. The importance of receptor recognition in target cell selection by reovirus implicates the σ1 protein as the primary effector of disease outcome. However, the contribution of σ1s to reovirus disease is unknown. To define the function of σ1s in reovirus pathogenesis, we generated a σ1s-deficient virus by altering a single nucleotide to disrupt the σ1s translational start site. Viruses were recovered that contain nine gene segments from strain type 3 Dearing and either the wild-type or σ1s-null S1 gene segment from strain type 1 Lang. Following peroral inoculation of newborn mice, both viruses replicated in the intestine, although the wild-type virus achieved higher yields than the σ1s-null virus. However, unlike the wild-type virus, the σ1s-deficient virus failed to disseminate to sites of secondary viral replication, including the brain, heart, and liver. Within the small intestine, both viruses were detected in Peyer's patches, but only the wild-type virus reached the mesenteric lymph node. Concordantly, wild-type virus, but not σ1s-deficient virus, was detected in the blood of infected animals. Wild-type and σ1s-null viruses produced equivalent titers following intracranial inoculation, indicating that σ1s is dispensable for viral growth in the murine CNS. These results suggest a key role for σ1s in virus spread from intestinal lymphatics to the bloodstream, thereby allowing the establishment of viremia and dissemination to sites of secondary replication within the infected host.",,"['Boehme, Karl W.', 'Guglielmi, Kristen M.', 'Dermody, Terence S.']",,,,
,PMC,Smallpox Vaccines for Biodefense,http://dx.doi.org/10.1016/j.vaccine.2009.07.103,PMC2764553,,,"Few diseases can match the enormous impact that smallpox has had on mankind. Its influence can be seen in the earliest recorded histories of ancient civilizations in Egypt and Mesopotamia. With fatality rates up to 30%, smallpox left its survivors with extensive scarring and other serious sequelae. It is estimated that smallpox killed 500 million people in the 19(th) and 20(th) centuries. Given the ongoing concerns regarding the use of variola as a biological weapon, this review will focus on the licensed vaccines as well as current research into next-generation vaccines to protect against smallpox and other poxviruses.",,"['Kennedy, Richard B.', 'Ovsyannikova, Inna', 'Poland, Gregory A.']",,,,
,PMC,"Helical Conformation of the SEVI Precursor Peptide PAP(248-286), a Dramatic Enhancer of HIV Infectivity, Promotes Lipid Aggregation and Fusion",http://dx.doi.org/10.1016/j.bpj.2009.08.034,PMC2770606,,,"In previous in vivo studies, amyloid fibers formed from a peptide ubiquitous in human seminal fluid (semen-derived enhancer of viral infection (SEVI)) were found to dramatically enhance the infectivity of the HIV virus (3–5 orders of magnitude by some measures). To complement those studies, we performed in vitro assays of PAP(248-286), the most active precursor to SEVI, and other polycationic polymers to investigate the physical mechanisms by which the PAP(248-286) promotes the interaction with lipid bilayers. At acidic (but not at neutral) pH, freshly dissolved PAP(248-286) catalyzes the formation of large lipid flocculates in a variety of membrane compositions, which may be linked to the promotion of convective transport in the vaginal environment rather than transport by a random Brownian motion. Furthermore, PAP(248-286) is itself fusiogenic and weakens the integrity of the membrane in such a way that may promote fusion by the HIV gp41 protein. An α-helical conformation of PAP(248-286), lying parallel to the membrane surface, is implicated in promoting bridging interactions between membranes by the screening of the electrostatic repulsion that occurs when two membranes are brought into close contact. This suggests that nonspecific binding of monomeric or small oligomeric forms of SEVI in a helical conformation to lipid membranes may be an additional mechanism by which SEVI enhances the infectivity of the HIV virus.",,"['Brender, Jeffrey R.', 'Hartman, Kevin', 'Gottler, Lindsey M.', 'Cavitt, Marchello E.', 'Youngstrom, Daniel W.', 'Ramamoorthy, Ayyalusamy']",,,,
,PMC,"Integrity of the Early Secretory Pathway Promotes, but Is Not Required for, Severe Acute Respiratory Syndrome Coronavirus RNA Synthesis and Virus-Induced Remodeling of Endoplasmic Reticulum Membranes",http://dx.doi.org/10.1128/JVI.01826-09,PMC2798390,,,"To accommodate its RNA synthesis in the infected cell, severe acute respiratory syndrome coronavirus (SARS-CoV) induces a cytoplasmic reticulovesicular network (RVN) that is derived from endoplasmic reticulum (ER) membranes. We set out to investigate how the early secretory pathway interacts with the RVN and the viral replication/transcription complex (RTC) that is anchored to it. When the secretory pathway was disrupted by brefeldin A (BFA) treatment at the start of infection, RVN formation and viral RTC activity were not blocked and continued up to 11 h postinfection, although RNA synthesis was reduced by ca. 80%. In vitro RTC assays, using membrane fractions from infected cells, demonstrated that BFA does not directly interfere with the activity of the viral RNA-synthesizing enzymes. Confocal microscopy studies showed that early secretory pathway components are not associated with SARS-CoV-induced replication sites, although our studies revealed that infection induces a remarkable redistribution of the translocon subunit Sec61α. Ultrastructural studies, including electron tomography, revealed that the formation of the RVN and all its previously documented features can occur in the presence of BFA, despite differences in the volume and morphology of the network. We therefore conclude that early secretory pathway proteins do not play a direct role in RVN morphogenesis or the functionality of the SARS-CoV RTC. The BFA-induced disruption of ER integrity and functionality probably affects the overall quality of the membrane scaffold that is needed to support the viral RTC and/or the availability of specific host factors, which in turn compromises viral RNA synthesis.",,"['Knoops, Kèvin', 'Swett-Tapia, Cindy', 'van den Worm, Sjoerd H. E.', 'te Velthuis, Aartjan J. W.', 'Koster, Abraham J.', 'Mommaas, A. Mieke', 'Snijder, Eric J.', 'Kikkert, Marjolein']",,,,
,PMC,Ebolavirus VP24 Binding to Karyopherins Is Required for Inhibition of Interferon Signaling,http://dx.doi.org/10.1128/JVI.01372-09,PMC2798383,,,"The Ebolavirus VP24 protein counteracts alpha/beta interferon (IFN-α/β) and IFN-γ signaling by blocking the nuclear accumulation of tyrosine-phosphorylated STAT1 (PY-STAT1). According to the proposed model, VP24 binding to members of the NPI-1 subfamily of karyopherin alpha (KPNα) nuclear localization signal receptors prevents their binding to PY-STAT1, thereby preventing PY-STAT1 nuclear accumulation. This study now identifies two domains of VP24 required for inhibition of IFN-β-induced gene expression and PY-STAT1 nuclear accumulation. We demonstrate that loss of function correlates with loss of binding to KPNα proteins. Thus, the VP24 IFN antagonist function requires the ability of VP24 to interact with KPNα.",,"['Mateo, Mathieu', 'Reid, St. Patrick', 'Leung, Lawrence W.', 'Basler, Christopher F.', 'Volchkov, Viktor E.']",,,,
,PMC,The Open Reading Frame 3a Protein of Severe Acute Respiratory Syndrome-Associated Coronavirus Promotes Membrane Rearrangement and Cell Death,http://dx.doi.org/10.1128/JVI.01662-09,PMC2798367,,,"The genome of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) contains eight open reading frames (ORFs) that encode novel proteins. These accessory proteins are dispensable for in vitro and in vivo replication and thus may be important for other aspects of virus-host interactions. We investigated the functions of the largest of the accessory proteins, the ORF 3a protein, using a 3a-deficient strain of SARS-CoV. Cell death of Vero cells after infection with SARS-CoV was reduced upon deletion of ORF 3a. Electron microscopy of infected cells revealed a role for ORF 3a in SARS-CoV induced vesicle formation, a prominent feature of cells from SARS patients. In addition, we report that ORF 3a is both necessary and sufficient for SARS-CoV-induced Golgi fragmentation and that the 3a protein accumulates and localizes to vesicles containing markers for late endosomes. Finally, overexpression of ADP-ribosylation factor 1 (Arf1), a small GTPase essential for the maintenance of the Golgi apparatus, restored Golgi morphology during infection. These results establish an important role for ORF 3a in SARS-CoV-induced cell death, Golgi fragmentation, and the accumulation of intracellular vesicles.",,"['Freundt, Eric C.', 'Yu, Li', 'Goldsmith, Cynthia S.', 'Welsh, Sarah', 'Cheng, Aaron', 'Yount, Boyd', 'Liu, Wei', 'Frieman, Matthew B.', 'Buchholz, Ursula J.', 'Screaton, Gavin R.', 'Lippincott-Schwartz, Jennifer', 'Zaki, Sherif R.', 'Xu, Xiao-Ning', 'Baric, Ralph S.', 'Subbarao, Kanta', 'Lenardo, Michael J.']",,,,
,PMC,The Anti-Helminthic Niclosamide Inhibits Wnt/Frizzled1 Signaling,http://dx.doi.org/10.1021/bi9009677,PMC2801776,,,"Wnt proteins bind to seven-transmembrane Frizzled receptors to mediate the important developmental, morphogenetic, and tissue-regenerative effects of Wnt signaling. Dysregulated Wnt signaling is associated with many cancers. Currently there exist no drug candidates, or even tool compounds that modulate Wnt-mediated receptor trafficking, and subsequent Wnt signaling. We examined libraries of FDA-approved drugs for their utility as Frizzled internalization modulators, employing a primary imaged-based GFP-fluorescence assay that uses Frizzled1 endocytosis as the readout. We now report that the anti-helminthic niclosamide, a drug used for the treatment of tapeworm, promotes Frizzled1 endocytosis, down regulates Dishevelled-2 protein, and inhibits Wnt3A-stimulated β-catenin stabilization and LEF/TCF reporter activity. Additionally, following niclosamide mediated internalization, the Frizzled1 receptor co-localizes in vesicles containing Transferrin and agonist-activated β(2)-adrenergic receptor. Therefore, niclosamide may serve as a negative modulator of Wnt/Frizzled1 signaling by depleting up-stream signaling molecules (i.e. Frizzled and Dishevelled), and moreover may provide a valuable means to study the physiological consequences of Wnt signaling.",,"['Chen, Minyong', 'Wang, Jiangbo', 'Lu, Jiuyi', 'Bond, Michael C.', 'Ren, Xiu-Rong', 'Lyerly, H. Kim', 'Barak, Larry S.', 'Chen, Wei']",,,,
,PMC,"Influenza, solar radiation and vitamin D",http://dx.doi.org/10.4161/derm.1.6.11357,PMC3092571,,,"The annual death numbers of influenza and pneumonia in Norway were studied for the time period 1980–2000. No direct relationships were found with the variations of the annual UVB fluences, probably due to the fact that these variations did not exceed 30%. However, there was a very pronounced seasonal variation of both influenza deaths and pneumonia deaths, the vast majority occurring during the winter. Vitamin D levels were also estimated from several publications. The data support the hypothesis that a high vitamin D level, as that found in the summer, acts in a protective manner with respect to influenza as well as pneumonia. The findings are discussed and compared with data from tropical and subtropical areas.",,"['Moan, Johan', 'Dahlback, Arne', 'Ma, LiWei', 'Juzeniene, Asta']",,,,
,PMC,Influenza virus M2 protein inhibits epithelial sodium channels by increasing reactive oxygen species,http://dx.doi.org/10.1096/fj.09-135590,PMC2775009,,,"The mechanisms by which replicating influenza viruses decrease the expression and function of amiloride-sensitive epithelial sodium channels (ENaCs) have not been elucidated. We show that expression of M2, a transmembrane influenza protein, decreases ENaC membrane levels and amiloride-sensitive currents in both Xenopus oocytes, injected with human α-, β-, and γ-ENaCs, and human airway cells (H441 and A549), which express native ENaCs. Deletion of a 10-aa region within the M2 C terminus prevented 70% of this effect. The M2 ENaC down-regulation occurred at normal pH and was prevented by MG-132, a proteasome and lysosome inhibitor. M2 had no effect on Liddle ENaCs, which have decreased affinity for Nedd4-2. H441 and A549 cells transfected with M2 showed higher levels of reactive oxygen species, as shown by the activation of redox-sensitive dyes. Pretreatment with glutathione ester, which increases intracellular reduced thiol concentrations, or protein kinase C (PKC) inhibitors prevented the deleterious effects of M2 on ENaCs. The data suggest that M2 protein increases steady-state concentrations of reactive oxygen intermediates that simulate PKC and decrease ENaCs by enhancing endocytosis and its subsequent destruction by the proteasome. These novel findings suggest a mechanism for the influenza-induced rhinorrhea and life-threatening alveolar edema in humans.—Lazrak, A., Iles, K. E., Liu, G. Noah, D. L., Noah, J. W., Matalon, S. Influenza virus M2 protein inhibits epithelial sodium channels by increasing reactive oxygen species.",,"['Lazrak, Ahmed', 'Iles, Karen E.', 'Liu, Gang', 'Noah, Diana L.', 'Noah, James W.', 'Matalon, Sadis']",,,,
,PMC,Is systems biology the key to preventing the next pandemic?,http://dx.doi.org/10.2217/fvl.09.53,PMC2843927,,,"Sporadic outbreaks of epizootics including SARS coronavirus and H5N1 avian influenza remind us of the potential for communicable diseases to quickly spread into worldwide epidemics. To confront emerging viral threats, nations have implemented strategies to prepare for pandemics and to control virus spread. Despite improved surveillance and quarantine measures, we find ourselves in the midst of a H1N1 influenza pandemic. Effective therapeutics and vaccines are essential to protect against current and future pandemics. The best route to effective therapeutics and vaccines is through a detailed and global view of virus–host interactions that can be achieved using a systems biology approach. Here, we provide our perspective on the role of systems biology in deepening our understanding of virus–host interactions and in improving drug and vaccine development. We offer examples from influenza virus research, as well as from research on other pandemics of our time – HIV/AIDS and HCV – to demonstrate that systems biology offers one possible key to stopping the cycle of viral pandemics.",,"['Tisoncik, Jennifer R', 'Belisle, Sarah E', 'Diamond, Deborah L', 'Korth, Marcus J', 'Katze, Michael G']",,,,
,PMC,Structural Genomics and Drug Discovery for Infectious Diseases,,PMC2789569,,,"The application of structural genomics methods and approaches to proteins from organisms causing infectious diseases is making available the three dimensional structures of many proteins that are potential drug targets and laying the groundwork for structure aided drug discovery efforts. There are a number of structural genomics projects with a focus on pathogens that have been initiated worldwide. The Center for Structural Genomics of Infectious Diseases (CSGID) was recently established to apply state-of-the-art high throughput structural biology technologies to the characterization of proteins from the National Institute for Allergy and Infectious Diseases (NIAID) category A–C pathogens and organisms causing emerging, or re-emerging infectious diseases. The target selection process emphasizes potential biomedical benefits. Selected proteins include known drug targets and their homologs, essential enzymes, virulence factors and vaccine candidates. The Center also provides a structure determination service for the infectious disease scientific community. The ultimate goal is to generate a library of structures that are available to the scientific community and can serve as a starting point for further research and structure aided drug discovery for infectious diseases. To achieve this goal, the CSGID will determine protein crystal structures of 400 proteins and protein-ligand complexes using proven, rapid, highly integrated, and cost-effective methods for such determination, primarily by X-ray crystallography. High throughput crystallographic structure determination is greatly aided by frequent, convenient access to high-performance beamlines at third-generation synchrotron X-ray sources.",,"Anderson, W. F.",,,,
,PMC,"Cystitis, Pyelonephritis, and Urolithiasis in Rats Accidentally Fed a Diet Deficient in Vitamin A",,PMC2786935,,,"Female Sprague–Dawley rats (n = 100; age, 3 wk) were fed diets that included a vitamin premix and either albumin or milk powder. Rats fed the albumin diet gained weight more slowly than did the other group. Between 19 and 28 wk of being fed the albumin diet, 12 rats died of bacterial cystitis and pyelonephritis. In addition, 2 more rats from the same dietary group developed peritonitis after ovariohysterectomy. Examination of the 44 rats fed the albumin diet that completed the 34-wk experiment revealed pyelonephritis in 68%, cystitis in 66%, urolithiasis in 27%, and nephrolithiasis in 5%. Squamous metaplasia of the transitional epithelium was present in all 44 rats, although other epithelia were histologically normal. Vitamin A deficiency was diagnosed after analyses of blood and liver samples. Analysis of the vitamin premix revealed approximately 25% of the expected amount of vitamin A. Because the milk powder contained sufficient vitamin A, deficiency did not occur in rats fed the milk powder diet. The major consequences of vitamin A deficiency in the rats were squamous metaplasia, bacterial infection, and calculus formation within the urinary tract. This report illustrates the importance of careful formulation and storage of vitamin premixes used in experimental diets. Vitamin A deficiency should be considered in rats with decreased weight gain and urinary tract disease even if ocular lesions are not present.",,"['Munday, John S', 'McKinnon, Hilary', 'Aberdein, Danielle', 'Collett, Mark G', 'Parton, Kathleen', 'Thompson, Keith G']",,,,
,PMC,Minimizing Trauma to the Upper Airway: A Ferret Model of Neonatal Intubation,,PMC2786933,,,"Our objective was to determine whether an adult ferret can be intubated as many as 10 times per training session without resulting in trauma to the upper airway. In this program, 8 male ferrets rotated through intubation laboratories, limiting the use of each animal to once every 3 mo. Animals were examined by the veterinary staff after intubations to assess for trauma to upper airway tissue. Each examination was given a trauma grade of 0 for no visible signs of trauma, 1 if erythema of the larynx was present, 2 if visible excoriation of the mucus membranes was present, and 3 if bleeding (frank hemorrhage) was observed. The number of intubation attempts was restricted to 10 per animal per training session. A total of 170 intubations were completed on the ferrets during a 12-mo period. The average number of intubations per laboratory was 8.1 intubations per ferret. In addition, 1.8% of the intubations resulted in erythema (score, 1) after training, and 0.6% of the intubations resulted in excoriation (score, 2). Frank hemorrhage (score, 3) was not noted. The overall percentage of intubations resulting in any trauma during a training session was 0.02%. None of the animals have experienced any major complications to date. This ongoing training program has been used to teach neonatal intubation skills to emergency medicine residents for the past 12 mo. Ensuring the health and safety of the ferrets was paramount. Our results suggest that as many as 10 intubation attempts per session can be performed safely on each ferret without causing excessive trauma.",,"['Kircher, Sara S', 'Murray, Len E', 'Juliano, Michael L']",,,,
,PMC,Interferon priming enables cells to partially overturn the SARS coronavirus-induced block in innate immune activation,http://dx.doi.org/10.1099/vir.0.013599-0,PMC2888313,,,"SARS coronavirus (SARS-CoV) is known to efficiently suppress the induction of antiviral type I interferons (IFN-α/β) in non-lymphatic cells through inhibition of the transcription factor IRF-3. Plasmacytoid dendritic cells, in contrast, respond to infection with production of high levels of IFNs. Here, we show that pretreatment of non-lymphatic cells with small amounts of IFN-α (IFN priming) partially overturns the block in IFN induction imposed by SARS-CoV. IFN priming combined with SARS-CoV infection substantially induced genes for IFN induction, IFN signalling, antiviral effector proteins, ubiquitination and ISGylation, antigen presentation and other cytokines and chemokines, whereas each individual treatment had no major effect. Curiously, however, despite this typical IFN response, neither IRF-3 nor IRF-7 was transported to the nucleus as a sign of activation. Taken together, our results suggest that (i) IFN, as it is produced by plasmacytoid dendritic cells, could enable tissue cells to launch a host response to SARS-CoV, (ii) IRF-3 and IRF-7 may be active at subdetectable levels, and (iii) SARS-CoV does not activate IRF-7.",,"['Kuri, Thomas', 'Zhang, Xiaonan', 'Habjan, Matthias', 'Martínez-Sobrido, Luis', 'García-Sastre, Adolfo', 'Yuan, Zhenghong', 'Weber, Friedemann']",,,,
,PMC,Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections,http://dx.doi.org/10.1099/vir.0.014001-0,PMC2862479,,,"The innate immune response is critical for host defence against respiratory coronaviruses (CoVs). This study demonstrated that an ongoing respiratory virus infection compromises innate immune responses and affects the pathogenesis of a respiratory CoV co-infection. An innate immunosuppressive respiratory virus infection was established by infecting weaned pigs with porcine reproductive and respiratory syndrome virus (PRRSV); 10 days later, the pigs were exposed to porcine respiratory coronavirus (PRCV). The PRRSV/PRCV dual-infected pigs had reduced weight gains, a higher incidence of fever and more severe pneumonia compared with either single infection. Significant suppression of innate immune responses [reduced alpha interferon (IFN-α) levels in the lungs and reduced blood natural killer cell cytotoxicity] by the ongoing PRRSV infection was observed in dual-infected pigs, which coincided with exacerbated pneumonia during early PRCV infection. The subsequent PRCV infection led to enhanced PRRSV replication in the lungs and a trend towards increased serum T-helper type 1 (Th1) (IFN-γ) but decreased Th2 [interleukin (IL)-4] responses, further exacerbating PRRSV pneumonia. Following PRCV infection, more severe PRRSV-related pulmonary alveolar macrophage (PAM) apoptosis occurred, as determined by an in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay, suggesting increased PRRSV replication in PAMs. Collectively, these observations suggest interactive effects between PRCV and PRRSV via early innate (IFN-α) and later adaptive Th1 (IFN-γ) and Th2 (IL-4) immune responses. These findings imply that an existing immunomodulating respiratory viral co-infection may be a contributing factor to more severe pneumonia in respiratory CoV disease. This study provides new insights into host–pathogen interactions related to co-infection by CoVs and other respiratory viruses.",,"['Jung, Kwonil', 'Renukaradhya, Gourapura J.', 'Alekseev, Konstantin P.', 'Fang, Ying', 'Tang, Yuxin', 'Saif, Linda J.']",,,,
,PMC,Evaluation of Pre-Analytical Variables in the Quantification of Dengue Virus by Real-Time Polymerase Chain Reaction,http://dx.doi.org/10.2353/jmoldx.2009.080164,PMC2765752,,,"An accurate molecular diagnosis for viral pathogens is highly dependent on pre-analytical procedures. The efficiencies of two viral RNA extraction methods (liquid phase partition and silica-based adsorption chromatography) and the effects of handling and storage on the stability of RNA isolated from dengue virus (DENV) were studied. Viral RNA extracted from spiked sera or clinical samples characterized with DENV infection were quantified by TaqMan real-time PCR. The presence of high serum proteins severely affected the recovery of DENV RNA by the liquid phase partition, but not the silica-based method. The recovery with Trizol liquid phase partition method was significantly improved by a concomitant addition of a co-precipitant and the reduction of sera proteins, resulting in recoveries similar to that of the silica-based methods. Repeated freeze-thaw cycles did not affect the recovery of viral RNA. While intact DENV was found to be stable in serum for up to 2 hour at 25°C, recovery of viral RNA from sera stored in the lysis/binding buffer was stable for up to 5 days. These data indicate that the choice of viral RNA extraction methods, the conditions for handling, and storing of clinical sera critically affect the quantification of viral nucleic acid from clinical samples. This will impact the accuracy and reproducibility of DENV diagnosis by PCR-based assays.",,"['Anwar, Azlinda', 'Wan, Guoqiang', 'Chua, Kaw-Bing', 'August, Joseph Thomas', 'Too, Heng-Phon']",,,,
,PMC,Broadly reactive pan-paramyxovirus reverse transcription polymerase chain reaction and sequence analysis for the detection of Canine distemper virus in a case of canine meningoencephalitis of unknown etiology,,PMC5052812,,,"Despite the immunologic protection associated with routine vaccination protocols, Canine distemper virus (CDV) remains an important pathogen of dogs. Antemortem diagnosis of systemic CDV infection may be made by reverse transcription polymerase chain reaction (RT-PCR) and/or immunohistochemical testing for CDV antigen; central nervous system infection often requires postmortem confirmation via histopathology and immunohistochemistry. An 8-month-old intact male French Bulldog previously vaccinated for CDV presented with multifocal neurologic signs. Based on clinical and postmortem findings, the dog’s disease was categorized as a meningoencephalitis of unknown etiology. Broadly reactive, pan-paramyxovirus RT-PCR using consensus-degenerate hybrid oligonucleotide primers, combined with sequence analysis, identified CDV amplicons in the dog’s brain. Immunohistochemistry confirmed the presence of CDV antigens, and a specific CDV RT-PCR based on the phosphoprotein gene identified a wild-type versus vaccinal virus strain. This case illustrates the utility of broadly reactive PCR and sequence analysis for the identification of pathogens in diseases with unknown etiology.",,"['Schatzberg, Scott J.', 'Li, Qiang', 'Porter, Brian F.', 'Barber, Renee M.', 'Claiborne, Mary Kate', 'Levine, Jonathan M.', 'Levine, Gwendolyn J.', 'Israel, Sarah K.', 'Young, Benjamin D.', 'Kiupel, Matti', 'Greene, Craig', 'Ruone, Susan', 'Anderson, Larry', 'Tong, Suxiang']",,,,
,PMC,La grippe pandémique H1N1 2009 et les controverses entourant le contrôle de l’infection : Travailler dans un contexte de changements continus,,PMC2806087,,,,,"Moore, DL",,,,
,PMC,Pandemic influenza (H1N1) 2009 and infection control controversies: Working with ongoing change,,PMC2806086,,,,,"Moore, DL",,,,
,PMC,Viruses and autophagy,http://dx.doi.org/10.1002/rmv.630,PMC2852112,,,"Autophagy is an evolutionarily conserved intracellular process by which bulk cytoplasm is enveloped inside a double-membraned vesicle and shuttled to lysosomes for degradation. Within the last 15 years, the genes necessary for the execution of autophagy have been identified and the number of tools for studying this process has grown. Autophagy is essential for tissue homeostasis and development and defective autophagy is associated with a number of diseases. As intracellular parasites, during the course of an infection, viruses encounter autophagy and interact with the proteins that execute this process. Autophagy and/or autophagy genes likely play both anti-viral and proviral roles in the life cycles and pathogenesis of many different virus families. With respect to anti-viral roles, the autophagy proteins function in targeting viral components or virions for lysosomal degradation in a process termed xenophagy, and they also play a role in the initiation of innate and adaptive immune system responses to viral infections. Consistent with this anti-viral role of host autophagy, some viruses encode virulence factors that interact with the host autophagy machinery and block the execution of autophagy. In contrast, other viruses appear to utilise components of the autophagic machinery to foster their own intracellular growth or non-lytic cellular egress. As the details of the role(s) of autophagy in viral pathogenesis become clearer, new anti-viral therapies could be developed to inhibit the beneficial and enhance the destructive aspects of autophagy on the viral life cycle.",,"['Kudchodkar, Sagar B.', 'Levine, Beth']",,,,
,PMC,Burden of tick-borne infections on American companion animals,http://dx.doi.org/10.1053/j.tcam.2009.06.005,PMC2802828,,,"This review examines the dynamics of tick biology and tick-borne infections in the United States. Clinical tick-borne diseases in dogs and cats are discussed. We demonstrate that there is much interest in tickborne infections at the level of the lay public (pet owners), describe trends in the distribution and prevalence of tickborne infections in the U.S., summarize some issues in understanding the degree of ill health due to tickborne infections, and suggest some avenues for research that would clarify these issues.",,"['Berrada, Zenda L.', 'Telford, Sam R.']",,,,
,PMC,"Comparative study of synonymous codon usage variations between the nucleocapsid and spike genes of coronavirus, and C-type lectin domain genes of human and mouse",http://dx.doi.org/10.3858/emm.2009.41.10.081,PMC2772977,,,"Coronaviruses (CoVs) are single-stranded RNA viruses which contain the largest RNA genomes, and severe acute respiratory syndrome coronavirus (SARS-CoV), a newly found group 2 CoV, emerged as infectious disease with high mortality rate. In this study, we compared the synonymous codon usage patterns between the nucleocapsid and spike genes of CoVs, and C-type lectin domain (CTLD) genes of human and mouse on the codon basis. Findings indicate that the nucleocapsid genes of CoVs were affected from the synonymous codon usage bias than spike genes, and the CTLDs of human and mouse partially overlapped with the nucleocapsid genes of CoVs. In addition, we observed that CTLDs which showed the similar relative synonymous codon usage (RSCU) patterns with CoVs were commonly derived from the human chromosome 12, and mouse chromosome 6 and 12, suggesting that there might be a specific genomic region or chromosomes which show a more similar synonymous codon usage pattern with viral genes. Our findings contribute to developing the codon-optimization method in DNA vaccines, and further study is needed to determine a specific correlation between the codon usage patterns and the chromosomal locations in higher organisms.",,"['Ahn, Insung', 'Jeong, Byeong-Jin', 'Son, Hyeon Seok']",,,,
,PMC,Obesity accelerates thymic aging,http://dx.doi.org/10.1182/blood-2009-03-213595,PMC2773495,,,"As the expanding obese population grows older, their successful immunologic aging will be critical to enhancing the health span. Obesity increases risk of infections and cancer, suggesting adverse effects on immune surveillance. Here, we report that obesity compromises the mechanisms regulating T-cell generation by inducing premature thymic involution. Diet-induced obesity reduced thymocyte counts and significantly increased apoptosis of developing T-cell populations. Obesity accelerated the age-related reduction of T-cell receptor (TCR) excision circle bearing peripheral lymphocytes, an index of recently generated T cells from thymus. Consistent with reduced thymopoiesis, dietary obesity led to reduction in peripheral naive T cells with increased frequency of effector-memory cells. Defects in thymopoiesis in obese mice were related with decrease in the lymphoid-primed multipotent progenitor (Lin(−)Sca1(+)Kit(+) Flt3(+)) as well as common lymphoid progenitor (Lin(−)Sca1(+)CD117(lo)CD127(+)) pools. The TCR spectratyping analysis showed that obesity compromised V-β TCR repertoire diversity. Furthermore, the obesity induced by melanocortin 4 receptor deficiency also constricted the T-cell repertoire diversity, recapitulating the thymic defects observed with diet-induced obesity. In middle-aged humans, progressive adiposity with or without type 2 diabetes also compromised thymic output. Collectively, these findings establish that obesity constricts T-cell diversity by accelerating age-related thymic involution.",,"['Yang, Hyunwon', 'Youm, Yun-Hee', 'Vandanmagsar, Bolormaa', 'Rood, Jennifer', 'Kumar, K. Ganesh', 'Butler, Andrew A.', 'Dixit, Vishwa Deep']",,,,
,PMC,"Rabies virus-based vaccines elicit neutralizing antibodies, poly-functional CD8(+) T cell, and protect rhesus macaques from AIDS-like disease after SIV(mac251) challenge",http://dx.doi.org/10.1016/j.vaccine.2009.10.051,PMC2826816,,,"Highly attenuated rabies virus (RV) vaccine vectors were evaluated for their ability to protect against highly pathogenic SIV(mac251) challenge. Mamu-A*01 negative rhesus macaques were immunized in groups of four with either: RV expressing SIV(mac239)-GagPol, a combination of RV expressing SIV(mac239)-Env and RV expressing SIV(mac239)-GagPol, or with empty RV vectors. Eight weeks later animals received a booster immunization with a heterologous RV expressing the same antigens. At twelve weeks post-boost, all animals were challenged intravenously with 100 TCID(50) of pathogenic SIV(mac251-CX). Immunized macaques in both vaccine groups had 1.3–1.6-log fold decrease in viral set point compared to control animals. The GagPol/Env immunized animals also had a significantly lower peak viral load. When compared to control animals following challenge, vaccinated macaques had a more rapid induction of SIV(mac251) neutralizing antibodies and of CD8(+) T cell responses to various SIV epitopes. Moreover, vaccinated macaques better-maintained peripheral memory CD4(+) T cells and were able to mount a poly-functional CD8(+) T cell response in the mucosa. These findings indicate promise for RV-based vectors and have important implications for the development of an efficacious HIV vaccine.",,"['Faul, Elizabeth J.', 'Aye, Pyone P.', 'Papaneri, Amy B.', 'Pahar, Bapi', 'McGettigan, James P.', 'Schiro, Faith', 'Chervoneva, Inna', 'Montefiori, David C.', 'Lackner, Andrew A.', 'Schnell, Matthias J.']",,,,
,PMC,Transient virulence of emerging pathogens,http://dx.doi.org/10.1098/rsif.2009.0384,PMC2874237,,,"Should emerging pathogens be unusually virulent? If so, why? Existing theories of virulence evolution based on a tradeoff between high transmission rates and long infectious periods imply that epidemic growth conditions will select for higher virulence, possibly leading to a transient peak in virulence near the beginning of an epidemic. This transient selection could lead to high virulence in emerging pathogens. Using a simple model of the epidemiological and evolutionary dynamics of emerging pathogens, along with rough estimates of parameters for pathogens such as severe acute respiratory syndrome, West Nile virus and myxomatosis, we estimated the potential magnitude and timing of such transient virulence peaks. Pathogens that are moderately evolvable, highly transmissible, and highly virulent at equilibrium could briefly double their virulence during an epidemic; thus, epidemic-phase selection could contribute significantly to the virulence of emerging pathogens. In order to further assess the potential significance of this mechanism, we bring together data from the literature for the shapes of tradeoff curves for several pathogens (myxomatosis, HIV, and a parasite of Daphnia) and the level of genetic variation for virulence for one (myxomatosis). We discuss the need for better data on tradeoff curves and genetic variance in order to evaluate the plausibility of various scenarios of virulence evolution.",,"['Bolker, Benjamin M.', 'Nanda, Arjun', 'Shah, Dharmini']",,,,
,PMC,Conserved Residues in the UL24 Protein of Herpes Simplex Virus 1 Are Important for Dispersal of the Nucleolar Protein Nucleolin,http://dx.doi.org/10.1128/JVI.01428-09,PMC2798432,,,"The UL24 family of proteins is widely conserved among herpesviruses. We demonstrated previously that UL24 of herpes simplex virus 1 (HSV-1) is important for the dispersal of nucleolin from nucleolar foci throughout the nuclei of infected cells. Furthermore, the N-terminal portion of UL24 localizes to nuclei and can disperse nucleolin in the absence of any other viral proteins. In this study, we tested the hypothesis that highly conserved residues in UL24 are important for the ability of the protein to modify the nuclear distribution of nucleolin. We constructed a panel of substitution mutations in UL24 and tested their effects on nucleolin staining patterns. We found that modified UL24 proteins exhibited a range of subcellular distributions. Mutations associated with a wild-type localization pattern for UL24 correlated with high levels of nucleolin dispersal. Interestingly, mutations targeting two regions, namely, within the first homology domain and overlapping or near the previously identified PD-(D/E)XK endonuclease motif, caused the most altered UL24 localization pattern and the most drastic reduction in its ability to disperse nucleolin. Viral mutants corresponding to the substitutions G121A and E99A/K101A both exhibited a syncytial plaque phenotype at 39°C. vUL24-E99A/K101A replicated to lower titers than did vUL24-G121A or KOS. Furthermore, the E99A/K101A mutation caused the greatest impairment of HSV-1-induced dispersal of nucleolin. Our results identified residues in UL24 that are critical for the ability of UL24 to alter nucleoli and further support the notion that the endonuclease motif is important for the function of UL24 during infection.",,"['Bertrand, Luc', 'Leiva-Torres, Gabriel André', 'Hyjazie, Huda', 'Pearson, Angela']",,,,
,PMC,Differential Downregulation of ACE2 by the Spike Proteins of Severe Acute Respiratory Syndrome Coronavirus and Human Coronavirus NL63,http://dx.doi.org/10.1128/JVI.01248-09,PMC2798380,,,"The human coronaviruses (CoVs) severe acute respiratory syndrome (SARS)-CoV and NL63 employ angiotensin-converting enzyme 2 (ACE2) for cell entry. It was shown that recombinant SARS-CoV spike protein (SARS-S) downregulates ACE2 expression and thereby promotes lung injury. Whether NL63-S exerts a similar activity is yet unknown. We found that recombinant SARS-S bound to ACE2 and induced ACE2 shedding with higher efficiency than NL63-S. Shedding most likely accounted for the previously observed ACE2 downregulation but was dispensable for viral replication. Finally, SARS-CoV but not NL63 replicated efficiently in ACE2-positive Vero cells and reduced ACE2 expression, indicating robust receptor interference in the context of SARS-CoV but not NL63 infection.",,"['Glowacka, Ilona', 'Bertram, Stephanie', 'Herzog, Petra', 'Pfefferle, Susanne', 'Steffen, Imke', 'Muench, Marcus O.', 'Simmons, Graham', 'Hofmann, Heike', 'Kuri, Thomas', 'Weber, Friedemann', 'Eichler, Jutta', 'Drosten, Christian', 'Pöhlmann, Stefan']",,,,
,PMC,Acceptability of A/H1N1 vaccination during pandemic phase of influenza A/H1N1 in Hong Kong: population based cross sectional survey,http://dx.doi.org/10.1136/bmj.b4164,PMC2768779,19861377,CC BY-NC,"Objective To investigate the intention of the Hong Kong general population to take up vaccination against influenza A/H1N1. Setting Cross sectional population based anonymous survey. Participants Random sample of 301 adults interviewed by telephone (response rate 80%). Main outcome measure Intention to take up vaccination against influenza A/H1N1 under five hypothetical scenarios: vaccination is free; vaccination per dosage costs less than $HK100 (£8; €9; $13), $HK101-200, or more than $HK200; and no data are available on the efficacy and safety of the vaccine. Results 45% (n=135) of the participants reported that they would be highly likely take up vaccination if it was free. When vaccination incurred a cost, however, the prevalence of uptake decreased: 36% (n=108) would take up vaccination if it cost less than $HK100, 24% (n=72) if it cost $HK101-200, and 15% (n=45) if it cost more than $HK200; and in absence of proved efficacy and safety decreased to 5% (n=14). Moreover, 32% (n=95) considered universal A/H1N1 vaccination unnecessary. Overall, 39% (n=117) of participants believed that A/H1N1 vaccination would prevent the virus being contracted; 63% (n=189) erroneously believed that efficacy of the vaccine had been confirmed by clinical trials, and 16% (n=49) believed that it is necessary for everyone in Hong Kong to take up vaccination against influenza A/H1N1. Conclusions The uptake of vaccination against influenza A/H1N1 by the general population of Hong Kong is unlikely to be high and would be sensitive to personal cost. Evidence about safety and efficacy is critical in determining the prevalence of uptake of vaccination.",2009 Oct 27,"['Lau, Joseph T F', 'Yeung, Nelson C Y', 'Choi, K C', 'Cheng, Mabel Y M', 'Tsui, H Y', 'Griffiths, Sian']",BMJ,,,
,PMC,Improved flu screening needed at airports,http://dx.doi.org/10.1503/cmaj.109-3053,PMC2764775,,,,,"Webster, Paul",,,,
,PMC,Considering population and war: a critical and neglected aspect of conflict studies,http://dx.doi.org/10.1098/rstb.2009.0151,PMC2781832,,,"This study analyses the relationship between war and population. The impact of the growth and decline of population on important types of warfare—great power, small power, civil war as well as terrorism—is illustrated, with the objective in each case to be descriptive of risk. I find that population change has a significant impact on each, with the greatest causal impact on small power conflicts, civil war and upon terrorism. I conclude with some reasons for guarded optimism about the incorporation of population as a component of analysis in the discipline of international studies, and for the potential to devise new solutions to prevent conflict.",,"Thayer, Bradley A.",,,,
,PMC,Innate immune responses to influenza A H5N1: friend or foe?,http://dx.doi.org/10.1016/j.it.2009.09.004,PMC5068224,,,"Avian influenza A H5N1 remains unusual in its virulence for humans. While infection of humans remains inefficient, many of those with H5N1 disease have a rapidly progressing viral pneumonia leading to acute respiratory distress syndrome and death but its pathogenesis remains an enigma. Comparisons in the virology and pathogenesis of human seasonal influenza viruses (H3N2 and H1N1) and H5N1 in patients, animal models and in relevant primary human cell cultures remains instructive. While the direct effects of viral replication and differences in the tropism of the virus for cells in the lower respiratory tract clearly contribute to the pathogenesis, we focus here on the possible contribution of the host innate immune response in the pathogenesis of this disease.",,"['Peiris, JSM', 'Cheung, CY', 'Leung, CYH', 'Nicholls, JM']",,,,
,PMC,A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral agents in vitro and in vivo,http://dx.doi.org/10.1016/j.virol.2009.09.023,PMC2787736,,,"Severe acute respiratory syndrome (SARS) is a highly lethal emerging disease caused by coronavirus SARS-CoV. New lethal animal models for SARS were needed to facilitate antiviral research. We adapted and characterized a new strain of SARS-CoV (strain v2163) that was highly lethal in 5–6 week old BALB/c mice. It had nine mutations affecting 10 amino acid residues. Strain v2163 increased IL-1α, IL-6, MIP-1α, MCP-1, and RANTES in mice, and high IL-6 expression correlated with mortality. The infection largely mimicked human disease, but lung pathology lacked hyaline membrane formation. In vitro efficacy against v2163 was shown with known inhihibitors of SARS-CoV replication. In v2163-infected mice, Ampligen™ was fully protective, stinging nettle lectin (UDA) was partially protective, ribavirin was disputable and possibly exacerbated disease, and EP128533 was inactive. Ribavirin, UDA and Ampligen™ decreased IL-6 expression. Strain v2163 provided a valuable model for anti-SARS research.",,"['Day, Craig W.', 'Baric, Ralph', 'Cai, Sui Xiong', 'Frieman, Matt', 'Kumaki, Yohichi', 'Morrey, John D.', 'Smee, Donald F.', 'Barnard, Dale L.']",,,,
,PMC,Outbreak of Acute Respiratory Disease Caused by Mycoplasma pneumoniae on Board a Deployed U.S. Navy Ship,http://dx.doi.org/10.1128/JCM.01926-09,PMC2786657,,,We identified 179 cases of acute respiratory illness including 50 cases of radiographically confirmed pneumonia over the course of 4 months on a deployed U.S. Navy vessel. Laboratory tests showed Mycoplasma pneumoniae to be the etiological agent. This report represents the first published description of a shipboard outbreak of this pathogen.,,"['Sliman, Joseph A.', 'Metzgar, David', 'Asseff, David C.', 'Coon, Robert G.', 'Faix, Dennis J.', 'Lizewski, Stephen']",,,,
,PMC,Multicenter Comparative Evaluation of Five Commercial Methods for Toxoplasma DNA Extraction from Amniotic Fluid,http://dx.doi.org/10.1128/JCM.01164-09,PMC2786637,,,"Over the past few years, a number of new nucleic acid extraction methods and extraction platforms using chemistry combined with magnetic or silica particles have been developed, in combination with instruments to facilitate the extraction procedure. The objective of the present study was to investigate the suitability of these automated methods for the isolation of Toxoplasma gondii DNA from amniotic fluid (AF). Therefore, three automated procedures were compared to two commercialized manual extraction methods. The MagNA Pure Compact (Roche), BioRobot EZ1 (Qiagen), and easyMAG (bioMérieux) automated procedures were compared to two manual DNA extraction kits, the QIAamp DNA minikit (Qiagen) and the High Pure PCR template preparation kit (Roche). Evaluation was carried out with two specific Toxoplasma PCRs (targeting the 529-bp repeat element), inhibitor search PCRs, and human beta-globin PCRs. The samples each consisted of 4 ml of AF with or without a calibrated Toxoplasma gondii RH strain suspension (0, 1, 2.5, 5, and 25 tachyzoites/ml). All PCR assays were laboratory-developed real-time PCR assays, using either TaqMan or fluorescent resonance energy transfer probes. A total of 1,178 PCRs were performed, including 978 Toxoplasma PCRs. The automated and manual methods were similar in sensitivity for DNA extraction from T. gondii at the highest concentration (25 Toxoplasma gondii cells/ml). However, our results showed that the DNA extraction procedures led to variable efficacy in isolating low concentrations of tachyzoites in AF samples (<5 Toxoplasma gondii cells/ml), a difference that might have repercussions since low parasite concentrations in AF exist and can lead to congenital toxoplasmosis.",,"['Yera, H.', 'Filisetti, D.', 'Bastien, P.', 'Ancelle, T.', 'Thulliez, P.', 'Delhaes, L.']",,,,
,PMC,Identification of a new region of SARS-CoV S protein critical for viral entry,http://dx.doi.org/10.1016/j.jmb.2009.10.032,PMC2794126,,,"Infection by SARS-CoV is initiated by specific interactions between the SARS-CoV spike (S) protein and its receptor ACE2. In this report, we screened a peptide library representing the SARS-CoV S protein sequence using an HIV-based pseudotyping system to identify specific regions that affect viral entry. One of the 169 peptides screened, peptide 9626 (S residues 217–234), inhibited SARS-CoV S-mediated entry of the pseudotyped virions in 293T cells expressing a functional SARS-CoV receptor (hACE2) in a dose dependent manner (IC50 ~11 µM). Alanine scanning mutagenesis was performed to assess the roles of individual residues within this region of S, which was previously uncharacterized. The effects included significant reductions in expression (K223A), viral incorporation (L218A, I230A and N232A), and reduced viral entry (L224A, L226A, I228A, T231A and F233A). Taken together, these results reveal a new region of S protein that is crucial for SARS-CoV entry.",,"['Guo, Ying', 'Tisoncik, Jennifer', 'McReynolds, Susanna', 'Farzan, Michael', 'Prabhakar, Bellur S.', 'Gallagher, Thomas', 'Rong, Lijun', 'Caffrey, Michael']",,,,
,PMC,Murine Hepatitis Virus Nonstructural Protein 4 Regulates Virus-Induced Membrane Modifications and Replication Complex Function,http://dx.doi.org/10.1128/JVI.01772-09,PMC2798404,,,"Positive-strand RNA viruses induce modifications of cytoplasmic membranes to form replication complexes. For coronaviruses, replicase nonstructural protein 4 (nsp4) has been proposed to function in the formation and organization of replication complexes. Murine hepatitis virus (MHV) nsp4 is glycosylated at residues Asn176 (N176) and N237 during plasmid expression of nsp4 in cells. To test if MHV nsp4 residues N176 and N237 are glycosylated during virus replication and to determine the effects of N176 and N237 on nsp4 function and MHV replication, alanine substitutions of nsp4 N176, N237, or both were engineered into the MHV-A59 genome. The N176A, N237A, and N176A/N237A mutant viruses were viable, and N176 and N237 were glycosylated during infection of wild-type (wt) and mutant viruses. The nsp4 glycosylation mutants exhibited impaired virus growth and RNA synthesis, with the N237A and N176A/N237A mutant viruses demonstrating more profound defects in virus growth and RNA synthesis. Electron microscopic analysis of ultrastructure from infected cells demonstrated that the nsp4 mutants had aberrant morphology of virus-induced double-membrane vesicles (DMVs) compared to those infected with wt virus. The degree of altered DMV morphology directly correlated with the extent of impairment in viral RNA synthesis and virus growth of the nsp4 mutant viruses. The results indicate that nsp4 plays a critical role in the organization and stability of DMVs. The results also support the conclusion that the structure of DMVs is essential for efficient RNA synthesis and optimal replication of coronaviruses.",,"['Gadlage, Mark J.', 'Sparks, Jennifer S.', 'Beachboard, Dia C.', 'Cox, Reagan G.', 'Doyle, Joshua D.', 'Stobart, Christopher C.', 'Denison, Mark R.']",,,,
,PMC,A Forward Genetic Strategy Reveals Destabilizing Mutations in the Ebolavirus Glycoprotein That Alter Its Protease Dependence during Cell Entry,http://dx.doi.org/10.1128/JVI.01832-09,PMC2798398,,,"Ebolavirus (EBOV) entry into cells requires proteolytic disassembly of the viral glycoprotein, GP. This proteolytic processing, unusually extensive for an enveloped virus entry protein, is mediated by cysteine cathepsins, a family of endosomal/lysosomal proteases. Previous work has shown that cleavage of GP by cathepsin B (CatB) is specifically required to generate a critical entry intermediate. The functions of this intermediate are not well understood. We used a forward genetic strategy to investigate this CatB-dependent step. Specifically, we generated a replication-competent recombinant vesicular stomatitis virus bearing EBOV GP as its sole entry glycoprotein and used it to select viral mutants resistant to a CatB inhibitor. We obtained mutations at six amino acid positions in GP that independently confer complete resistance. All of the mutations reside at or near the GP1-GP2 intersubunit interface in the membrane-proximal base of the prefusion GP trimer. This region forms a part of the “clamp” that holds the fusion subunit GP2 in its metastable prefusion conformation. Biochemical studies suggest that most of the mutations confer CatB independence not by altering specific cleavage sites in GP but rather by inducing conformational rearrangements in the prefusion GP trimer that dramatically enhance its susceptibility to proteolysis. The remaining mutants did not show the preceding behavior, indicating the existence of multiple mechanisms for acquiring CatB independence during entry. Altogether, our findings suggest that CatB cleavage is required to facilitate the triggering of viral membrane fusion by destabilizing the prefusion conformation of EBOV GP.",,"['Wong, Anthony C.', 'Sandesara, Rohini G.', 'Mulherkar, Nirupama', 'Whelan, Sean P.', 'Chandran, Kartik']",,,,
,PMC,Immunopathogenesis of polymicrobial otitis media,http://dx.doi.org/10.1189/jlb.0709518,PMC2812561,19843575,CC BY-NC,"OM, or inflammation of the middle ear, is a highly prevalent infection in children worldwide. OM is a multifactorial disease with multiple risk factors, including preceding or concurrent viral URT infection. Hence, OM is also a polymicrobial disease. The mechanisms by which viruses predispose to bacterial OM are replete; however, all are predicated on the general principle of compromise of primary host airway defenses. Thus, despite an as-yet incomplete understanding of the molecular mechanisms involved in bacterial superinfection of a virus-compromised respiratory tract, the URT viruses are known to induce histopathology of airway mucosal epithelium, up-regulate expression of eukaryotic receptors used for bacterial adherence, alter the biochemical and rheological properties of airway mucus, and affect innate and acquired host immune functions, among others. Although discussed here in the context of OM, during preceding or concurrent viral infection of the human respiratory tract, viral impairment of airway defenses and the resulting predisposition to subsequent bacterial coinfection are also known to be operational in the mid and lower airway as well.",2010 Feb 20,"Bakaletz, Lauren O.",J Leukoc Biol,,,
,PMC,Peripatetic health-care workers as potential superspreaders,http://dx.doi.org/10.1073/pnas.0900974106,PMC2775324,,,"Many nosocomial outbreaks exhibit “superspreading events” in which cross-transmission occurs via a single individual to a large number of patients. We investigated how heterogeneity in Health-Care Worker (HCW) behaviors, especially compliance to hand hygiene, may cause superspreading events. In particular, we compared the superspreading potential of peripatetic (noncohorted) HCWs with that of other HCWs. We developed an agent-based model for hand transmission of a pathogen in a hospital ward. Three HCW profiles were allowed: 2 assigned profiles, one with frequent contacts with a limited number of patients, another with fewer contacts but with more patients; and one peripatetic profile, with a single daily contact with all patients. We used data from the literature on common nosocomial pathogens (Staphylococcus aureus, Enterococci). The average number of patients colonized over 1 month increases with noncompliance to hand hygiene. Importantly, we show that this increase depends on the profile of noncompliant HCWs; for instance, it remains low for a single noncompliant assigned HCW but can be quite large for a single noncompliant peripatetic HCW. Outbreaks with this single fully noncompliant peripatetic HCW (representing only 4.5% of the staff) are similar to those predicted when all HCWs are noncompliant following 23% of patient contacts. Noncompliant peripatetic HCWs may play a disproportionate role in disseminating pathogens in a hospital ward. Their unique profile makes them potential superspreaders. This suggests that average compliance to hygiene may not be a good indicator of nosocomial risk in real life health care settings with several HCW profiles.",,"['Temime, Laura', 'Opatowski, Lulla', 'Pannet, Yohan', 'Brun-Buisson, Christian', 'Boëlle, Pierre Yves', 'Guillemot, Didier']",,,,
,PMC,Serum IP-10 as a Biomarker of Human Rhinovirus Infection at Exacerbation of COPD,http://dx.doi.org/10.1378/chest.09-1541,PMC2851557,,,"BACKGROUND: Human rhinovirus (HRV) is the most frequent virus associated with COPD exacerbations. Viral infections increase exacerbation severity and likelihood of hospitalization. As ease of sampling blood makes serum a more practical marker than sputum, we investigated whether changes in serum interferon-γ-inducible protein 10 (IP-10) from baseline to exacerbation were higher in airway HRV-positive exacerbations and whether IP-10 levels related to HRV load. METHODS: One hundred thirty-six patients with COPD and 70 controls were included over 2 years and 72 exacerbations sampled. HRV positivity and load were determined by reverse transcriptase-polymerase chain reaction in nasopharyngeal swabs and/or sputum at baseline and exacerbation. IP-10 was measured by enzyme-linked immunosorbent assay in serum and compared with HRV load. RESULTS: At baseline, serum IP-10 was higher in patients with COPD than controls; medians were 149.4 pg/mL (103-215) and 111.7 pg/mL (82-178), P = .02. The presence of HRV at baseline did not increase IP-10: patients with COPD, 166.9 pg/mL (110-240) and 149.4 pg/mL (103-215), P = .30; controls, 136.4 pg/mL (77-204) and 111.7 pg/mL (82-178), P = .53. IP-10 increased significantly from baseline to exacerbation in HRV-positive exacerbations: 154.9 pg/mL (114.0-195.1) to 207.5 pg/mL (142.1-333.5), P = .009. There was no change in IP-10 between baseline and exacerbation in HRV-negative exacerbations: 168.3 pg/mL (94.3-249.8) and 175.6 pg/mL (107.2-290.4), P = .49. At exacerbation, IP-10 correlated with sputum viral load: rho = 0.48; P = .02. In receiver operating characteristics analysis, the combination of IP-10 and coryzal symptoms gave an area under the curve of 0.82 (95% CI, 0.74-0.90). CONCLUSIONS: IP-10 increases from baseline to exacerbation in HRV-positive exacerbations and correlates with sputum HRV load. Serum IP-10 may be useful as a novel marker for these events.",,"['Quint, Jennifer K.', 'Donaldson, Gavin C.', 'Goldring, James J.P.', 'Baghai-Ravary, Ramin', 'Hurst, John R.', 'Wedzicha, Jadwiga A.']",,,,
,PMC,Towards a small animal model for hepatitis C,http://dx.doi.org/10.1038/embor.2009.223,PMC2775186,,,"Hepatitis C virus (HCV) causes chronic liver disease and affects an estimated 3% of the world's population. Options for the prevention or therapy of HCV infection are limited; there is no vaccine and the nonspecific, interferon-based treatments now in use are frequently ineffective and have significant side effects. A small-animal model for HCV infection would significantly expedite antiviral compound development and preclinical testing, as well as open new avenues to decipher the mechanisms that underlie viral pathogenesis. The natural species tropism of HCV is, however, limited to humans and chimpanzees. Here, we discuss the prospects of developing a mouse model for HCV infection, taking into consideration recent results on HCV entry and replication, and new prospects in xenotransplantation biology. We highlight three independent, but possibly complementary, approaches towards overcoming current species barriers and generating a small-animal model for HCV pathogenesis.",,"['Ploss, Alexander', 'Rice, Charles M.']",,,,
,PMC,Profiling Carbohydrate-Receptor Interaction with Recombinant Innate Immunity Receptor-Fc Fusion Proteins,http://dx.doi.org/10.1074/jbc.M109.065961,PMC2787309,,,"The recognition of bacteria, viruses, fungi, and other microbes is controlled by host immune cells, which are equipped with many innate immunity receptors, such as Toll-like receptors, C-type lectin receptors, and immunoglobulin-like receptors. Our studies indicate that the immune modulating properties of many herbal drugs, for instance, the medicinal fungus Reishi (Ganoderma lucidum) and Cordyceps sinensis, could be attributed to their polysaccharide components. These polysaccharides specifically interact with and activate surface receptors involved in innate immunity. However, due to the complexity of polysaccharides and their various sources from medicinal fungi, quantitative analysis of medicinal polysaccharide extracts with regard to their functions represents a major challenge. To profile carbohydrate-immune receptor interactions, the extracellular domains of 17 receptors were cloned as Fc-fusion proteins, such that their interactions with immobilized polysaccharides could be probed in an enzyme-linked immunosorbent assay. The results show that several innate immune receptors, including Dectin-1, DC-SIGN, Langerin, Kupffer cell receptor, macrophage mannose receptor, TLR2, and TLR4, interact with the polysaccharide extracts from G. lucidum (GLPS). This analysis revealed distinct polysaccharide profiles from different sources of medicinal fungi, and the innate immune receptor-based enzyme-linked immunosorbent assay described here can serve as a high-throughput profiling method for the characterization and quality control of medicinal polysaccharides. It also provides a means to dissect the molecular mechanism of medicinal polysaccharide-induced immunomodulation events.",,"['Hsu, Tsui-Ling', 'Cheng, Shih-Chin', 'Yang, Wen-Bin', 'Chin, See-Wen', 'Chen, Bo-Hua', 'Huang, Ming-Ting', 'Hsieh, Shie-Liang', 'Wong, Chi-Huey']",,,,
,PMC,HIV-1 Transmission by Dendritic Cell-specific ICAM-3-grabbing Nonintegrin (DC-SIGN) Is Regulated by Determinants in the Carbohydrate Recognition Domain That Are Absent in Liver/Lymph Node-SIGN (L-SIGN),http://dx.doi.org/10.1074/jbc.M109.030619,PMC2804366,,,"In this study, we identify determinants in dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) necessary for human immunodeficiency virus, type 1 (HIV-1), transmission. Although human B cell lines expressing DC-SIGN efficiently capture and transmit HIV-1 to susceptible target cells, cells expressing the related molecule liver/lymph node-specific ICAM-3-grabbing nonintegrin (L-SIGN) do not. To understand the differences between DC-SIGN and L-SIGN that affect HIV-1 interactions, we developed Raji B cell lines expressing different DC-SIGN/L-SIGN chimeras. Testing of the chimeras demonstrated that replacement of the DC-SIGN carbohydrate-recognition domain (CRD) with that of L-SIGN was sufficient to impair virus binding and prevent transmission. Conversely, the ability to bind and transmit HIV-1 was conferred to L-SIGN chimeras containing the DC-SIGN CRD. We identified Trp-258 in the DC-SIGN CRD to be essential for HIV-1 transmission. Although introduction of a K270W mutation at the same position in L-SIGN was insufficient for HIV-1 binding, an L-SIGN mutant molecule with K270W and a C-terminal DC-SIGN CRD subdomain transmitted HIV-1. These data suggest that DC-SIGN structural elements distinct from the oligosaccharide-binding site are required for HIV-1 glycoprotein selectivity.",,"['Chung, Nancy P. Y.', 'Breun, Sabine K. J.', 'Bashirova, Arman', 'Baumann, Joerg G.', 'Martin, Thomas D.', 'Karamchandani, Jaideep M.', 'Rausch, Jason W.', 'Le Grice, Stuart F. J.', 'Wu, Li', 'Carrington, Mary', 'KewalRamani, Vineet N.']",,,,
,PMC,Pseudomonas fluorescens contamination of a feline packed red blood cell unit and studies of canine units,http://dx.doi.org/10.1111/j.1939-165X.2009.00190.x,PMC3111970,,,"BACKGROUND: While screening programs have reduced the risk of infectious disease transmission by donors in human and veterinary blood banking, bacterial contamination of blood products has emerged as a major complication in human medicine. OBJECTIVES: To describe a Pseudomonas fluorescens (Pf)-contaminated feline packed RBC (pRBC) unit and experimentally investigate Pf-contaminated canine pRBCs. METHODS: Canine pRBCs were inoculated with Pf-rich pRBCs from the sentinel feline unit and stored at 4°C or 20°C for 72 hours. Aliquots from the pRBCs were serially evaluated by microscopy, culture, and a eubacterial 16S rRNA real-time PCR assay. RESULTS: One Pf-contaminated feline unit turned black after 22 days of storage and was removed from the blood bank; a source was not found, and no other contaminated units were identified. Canine pRBCs spiked with 5 or 25 μL of the sentinel unit became culture- and/or 16S PCR-positive at ≥8 hours at 20°C and 48 hours at 4°C and developed a color change at ≥24 hours. Sensitivity studies indicated that without incubation, inoculation of ≥100 μL Pf-rich pRBCs was necessary for a positive 16S PCR test result. CONCLUSIONS: P. fluorescens grows in stored pRBCs slowly at 4°C and rapidly at 20°C. Screening of blood products for color change, estimating bacterial concentration with microscopy, and 16S PCR testing are simple and fast ways to detect bacteria in stored blood. Aseptic collection, temperature-controlled storage, and regular visual monitoring of stored units is recommended. Discolored units should not be transfused, but examined for bacterial contamination or other blood product quality problems.",,"['Kessler, Rebecca J.', 'Rankin, Shelley', 'Young, Sheri', 'O’Shea, Kathleen', 'Calabrese, Maria', 'Guldin, Amy', 'Lipson, Nicole', 'Oakley, Donna A.', 'Giger, Urs']",,,,
,PMC,Detection of Asymptomatic Antigenemia in Pigs Infected by Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) by a Novel Capture Immunoassay with Monoclonal Antibodies against the Nucleocapsid Protein of PRRSV,http://dx.doi.org/10.1128/CVI.00244-09,PMC2786387,,,"Routine surveillance for porcine reproductive and respiratory syndrome virus (PRRSV) infections is crucial for the epidemiological control of this disease. Antibody tests are widely used but cannot differentiate between vaccination and reinfection. We developed a PRRSV antigen capture enzyme-linked immunosorbent assay (ELISA) using well-characterized monoclonal antibodies (MAbs) raised against the nucleocapsid (N) protein of North American and European PRRSV. This antigen assay detected purified N protein from both genotypes at levels as low as 0.4 and 0.8 ng, respectively. The specificity and sensitivity of the N antigen assay were evaluated with ground lung tissues from 8 PRRSV-infected and 16 healthy swine, and culture supernatants from six PRRSV isolates as well as other swine viruses were confirmed by reverse transcriptase PCR (RT-PCR). Antigen assays were positive in all eight infected tissues and with six different PRRSV isolates, with no false positives among healthy tissues and other swine viruses (i.e., pseudorabies and foot and mouth disease viruses). A number of sera, field collected from 466 vaccinated and asymptomatic pigs in Guangdong, China, between 2008 and 2009, tested positive by the N antigen assay (12.45%), RT-PCR (15.02%), and a commercial test for antibodies against PRRSV (78.97%). Of the 466 sera, 47 were positive by both antigen and RT-PCR tests, 11 by antigen test only, and 23 by RT-PCR only; the two assays had an overall agreement of 92.7%, indicating a significant percentage of active PRRSV in asymptomatic pigs despite previous immunization. These findings suggest that the antigen assay is a valuable field tool for the epidemiological control of PRRSV that can be used for rapid screening, particularly in asymptomatic animals.",,"['Cai, Jian-Piao', 'Wang, Ya-Di', 'Tse, Herman', 'Xiang, Hua', 'Yuen, Kwok-Yung', 'Che, Xiao-Yan']",,,,
,PMC,Enhanced Viral Etiological Diagnosis of Respiratory System Infection Outbreaks by Use of a Multitarget Nucleic Acid Amplification Assay,http://dx.doi.org/10.1128/JCM.01469-09,PMC2786615,,,"A study was undertaken to assess the utility of the xTAG respiratory viral panel (RVP) for enhanced laboratory investigation of respiratory outbreaks. Specimens (n = 1,108) from 244 suspected respiratory virus outbreaks in 2006 and 2007 in Alberta, Canada, were included in the study. Testing by direct fluorescent antigen detection (DFA) and various in-house nucleic acid amplification tests (NATs) for common respiratory viruses provided an etiological diagnosis in 177 outbreaks (72.5%), with 524 samples testing positive (47.3%) for a respiratory virus. Two hundred samples from 51 unresolved outbreaks were further tested by RVP retrospectively. Fifty-eight samples from 30 unresolved outbreaks had a respiratory virus detected by RVP (47 picornavirus-positive, 9 coronavirus-positive, and 2 influenza virus A-positive samples). Overall, detection of a viral etiological agent was achieved in 90.8% of outbreaks using a combination of DFA, NATs, and RVP. Use of RVP enhances the laboratory investigation of respiratory virus outbreaks and facilitates appropriate patient and outbreak management.",,"['Wong, Sallene', 'Pabbaraju, Kanti', 'Lee, Bonita E.', 'Fox, Julie D.']",,,,
,PMC,Interactions and Oligomerization of Hantavirus Glycoproteins,http://dx.doi.org/10.1128/JVI.00481-09,PMC2798430,,,"In this report the basis for the structural architecture of the envelope of hantaviruses, family Bunyaviridae, is systematically studied by the interactions of two glycoproteins N and C (Gn and Gc, respectively) and their respective disulfide bridge-mediated homo- and heteromeric oligomerizations. In virion extracts Gn and Gc associated in both homo- and hetero-oligomers which were, at least partially, thiol bridge mediated. Due to strong homo-oligomerization, the hetero-oligomers of Gn and Gc are likely to be mediated by homo-oligomeric subunits. A reversible pH-induced disappearance of a neutralizing epitope in Gc and dissociation of the Gn-Gc complex at pH values below 6.2 provide proteochemical evidence for the fusogenicity of Gc. Incomplete inactivation of virions at acidic pH indicates that additional factors are required for hantavirus fusion, as in the case of pestiviruses of the Flaviviridae. Based on similarities to class II fusion proteins, a structure model was created of hantavirus Gc using the Semliki Forest virus E1 protein as a template. In total, 10 binding regions for Gn were found by peptide scanning, of which five represent homotypic (Gn(I) to Gn(V)) and five represent heterotypic (Gc(I) to Gc(V)) interaction sites that we assign as intra- and interspike connections, respectively. In conclusion, the glycoprotein associations were compiled to a model wherein the surface of hantaviruses is formed of homotetrameric Gn complexes interconnected with Gc homodimers. This organization would create the grid-like surface pattern described earlier for hantaviruses in negatively stained electron microscopy specimens.",,"['Hepojoki, Jussi', 'Strandin, Tomas', 'Vaheri, Antti', 'Lankinen, Hilkka']",,,,
,PMC,Nuclear Magnetic Resonance Structure of the Nucleic Acid-Binding Domain of Severe Acute Respiratory Syndrome Coronavirus Nonstructural Protein 3,http://dx.doi.org/10.1128/JVI.01253-09,PMC2786856,,,"The nuclear magnetic resonance (NMR) structure of a globular domain of residues 1071 to 1178 within the previously annotated nucleic acid-binding region (NAB) of severe acute respiratory syndrome coronavirus nonstructural protein 3 (nsp3) has been determined, and N- and C-terminally adjoining polypeptide segments of 37 and 25 residues, respectively, have been shown to form flexibly extended linkers to the preceding globular domain and to the following, as yet uncharacterized domain. This extension of the structural coverage of nsp3 was obtained from NMR studies with an nsp3 construct comprising residues 1066 to 1181 [nsp3(1066-1181)] and the constructs nsp3(1066-1203) and nsp3(1035-1181). A search of the protein structure database indicates that the globular domain of the NAB represents a new fold, with a parallel four-strand β-sheet holding two α-helices of three and four turns that are oriented antiparallel to the β-strands. Two antiparallel two-strand β-sheets and two 3(10)-helices are anchored against the surface of this barrel-like molecular core. Chemical shift changes upon the addition of single-stranded RNAs (ssRNAs) identified a group of residues that form a positively charged patch on the protein surface as the binding site responsible for the previously reported affinity for nucleic acids. This binding site is similar to the ssRNA-binding site of the sterile alpha motif domain of the Saccharomyces cerevisiae Vts1p protein, although the two proteins do not share a common globular fold.",,"['Serrano, Pedro', 'Johnson, Margaret A.', 'Chatterjee, Amarnath', 'Neuman, Benjamin W.', 'Joseph, Jeremiah S.', 'Buchmeier, Michael J.', 'Kuhn, Peter', 'Wüthrich, Kurt']",,,,
,PMC,The Bovine Immunodeficiency Virus Rev Protein: Identification of a Novel Lentiviral Bipartite Nuclear Localization Signal Harboring an Atypical Spacer Sequence,http://dx.doi.org/10.1128/JVI.01613-09,PMC2786839,,,"The bovine immunodeficiency virus (BIV) Rev protein (186 amino acids [aa] in length) is involved in the nuclear exportation of partially spliced and unspliced viral RNAs. Previous studies have shown that BIV Rev localizes in the nucleus and nucleolus of infected cells. Here we report the characterization of the nuclear/nucleolar localization signals (NLS/NoLS) of this protein. Through transfection of a series of deletion mutants of BIV Rev fused to enhanced green fluorescent protein and fluorescence microscopy analyses, we were able to map the NLS region between aa 71 and 110 of the protein. Remarkably, by conducting alanine substitution of basic residues within the aa 71 to 110 sequence, we demonstrated that the BIV Rev NLS is bipartite, maps to aa 71 to 74 and 95 to 101, and is predominantly composed of arginine residues. This is the first report of a bipartite Rev (or Rev-like) NLS in a lentivirus/retrovirus. Moreover, this NLS is atypical, as the length of the sequence between the motifs composing the bipartite NLS, e.g., the spacer sequence, is 20 aa. Further mutagenesis experiments also identified the NoLS region of BIV Rev. It localizes mainly within the NLS spacer sequence. In addition, the BIV Rev NoLS sequence differs from the consensus sequence reported for other viral and cellular nucleolar proteins. In summary, we conclude that the nucleolar and nuclear localizations of BIV Rev are mediated via novel NLS and NoLS motifs.",,"['Gomez Corredor, Andrea', 'Archambault, Denis']",,,,
,PMC,Plant-made vaccine antigens and biopharmaceuticals,http://dx.doi.org/10.1016/j.tplants.2009.09.009,PMC2787751,,,"Plant cells are ideal bioreactors for the production and oral delivery of vaccines and biopharmaceuticals, eliminating the need for expensive fermentation, purification, cold storage, transportation and sterile delivery. Plant-made vaccines have been developed for two decades but none has advanced beyond Phase I. However, two plant-made biopharmaceuticals are now advancing through Phase II and Phase III human clinical trials. In this review, we evaluate the advantages and disadvantages of different plant expression systems (stable nuclear and chloroplast or transient viral) and their current limitations or challenges. We provide suggestions for advancing this valuable concept for clinical applications and conclude that greater research emphasis is needed on large scale production, purification, functional characterization, oral delivery and preclinical evaluation.",,"['Daniell, Henry', 'Singh, Nameirakpam D.', 'Mason, Hugh', 'Streatfield, Stephen J.']",,,,
,PMC,Molecular epidemiology of feline immunodeficiency virus in the domestic cat (Felis catus),http://dx.doi.org/10.1016/j.vetimm.2009.10.011,PMC2821968,,,"Studying the evolutionary mechanisms of feline immunodeficiency virus in the domestic cat (Felis catus), FIV(Fca), provides a good comparison to other lentiviruses, such as HIV and FIV(Pco) in the cougar (Puma concolor). We review the current epidemiological and evolutionary findings of FIV(Fca),. In addition to the five accepted FIV(Fca), subtypes, several recent phylogenetic studies have found strains that form separate clades, indicative of novel subtypes. In New Zealand cats, these strains of unknown subtype have been found to be involved in complex patterns of intergenic recombination, and whole genome sequences are required to resolve these. Evidence of recombination events has been documented with the highest levels in the env gene, the region involved in host cell receptor recognition. Several cases of FIV(Fca), multiple infection, both inter- and intra-subtype, have been reported. The findings of both unknown subtypes and relatively high levels of recombination suggest the need for further testing of the current vaccine. Limited studies on the evolutionary rate of FIV(Fca), document a value twice to three times that of FIV in the cougar, a result suggesting the different levels of co-adaptation between the viruses and their respective hosts. We studied the tissue distribution of FIV(Fca), in feral domestic cats, finding the first case of FIV compartmentalisation, a phenomenon well-documented in HIV-1 patients.",,"['Hayward, Jessica J', 'Rodrigo, Allen G']",,,,
,PMC,Intramuscular immunization with a vesicular stomatitis virus recombinant expressing the influenza hemagglutinin provides post-exposure protection against lethal influenza challenge,http://dx.doi.org/10.1016/j.vaccine.2009.09.112,PMC2787752,,,"Vaccines currently licensed for the prevention of seasonal influenza induce antibodies against the influenza hemagglutinin (HA) and neuraminidase (NA) contained in the vaccine preparation but require at least two weeks after immunization for the development of protective immunity. These vaccines do not induce protective responses quickly enough to blunt the effects of infection when administered after exposure. We have developed a novel vaccine based on recombinant vesicular stomatitis virus which expresses the influenza hemagglutinin (rVSV HA) and protects mice from lethal influenza challenge when the vaccine is administered intramuscularly at least 24 hours after delivery of the influenza challenge virus. To our knowledge this is the first vaccine that effectively protects animals from lethal influenza challenge when delivered by a systemic route after influenza exposure has occurred. The induction of HA-specific immune responses by the vaccine is necessary for full protection from challenge, because animals immunized with an empty rVSV vector were not protected equally. Our results are consistent with a model in which vaccination induces an immediate antiviral cytokine response, followed by development of humoral and cellular immune responses which act to reduce pulmonary viral loads and accelerate recovery. Consistent with this model, mice vaccinated with the specific vaccine rVSV HA had high levels of IFN-α in the serum by 24 hours after challenge/vaccination, developed serum neutralizing Ab to influenza two days prior to control animals, and had detectable anti-HA CD8 T cells present in the peripheral blood three days prior to control mice.",,"['Barefoot, Brice E.', 'Athearn, Kathleen', 'Sample, Christopher J.', 'Ramsburg, Elizabeth A.']",,,,
,PMC,Age differences in dispositional optimism: a cross-cultural study,http://dx.doi.org/10.1007/s10433-009-0130-z,PMC5547345,,,"Testing the hypothesis that individuals develop their personal characteristics according to what their cultures emphasize, this cross-sectional study aimed at investigating how dispositional optimism varied with age among Americans and Hong Kong Chinese. The sample included 84 younger adults and 55 older adults that were equally distributed across the two cultures. Results revealed that older Americans displayed a higher level of dispositional optimism than did younger Americans; whereas older Chinese showed a lower level of dispositional optimism than did their younger counterparts. Findings shed light on the mixed findings on age-related dispositional optimism in the literature.",,"['You, Jin', 'Fung, Helene H. L.', 'Isaacowitz, Derek M.']",,,,
,PMC,Movement of airborne contaminants in a hospital isolation room,http://dx.doi.org/10.1098/rsif.2009.0319.focus,PMC2843951,,,"We analyse the characteristics of a force-ventilated isolation room, and the contributions to transport caused by the movement of people and doors opening/closing. The spread of fine droplets and particles can be understood, to leading order, by considering the movement of passive contaminants. A scaled (1:10) model of an isolation room (with water instead of air) was used to analyse the dilution of a passive contaminant (food dye), released either instantaneously or at a constant rate. The high level of turbulence, typical of isolation rooms, ensures that the dye concentration is uniform within the model room and mixing is perfect, and the measured mean concentration can be predicted theoretically. In a second series of experiments, the exchange generated by a door opening/closing is measured for different opening angles. A dipolar vortex is generated at the tip of the door which moves into the centre of the room, with a large coherent structure moving along the wall. The exchange volume is comparable to the swept volume of the door. Larger droplets and particles do not move passively. Their movement within a turbulent flow is studied by combining a Lagrangian model of particle movement with a kinematic simulation of a pseudo turbulent flow. The results show that while the mean fall velocity of particles is largely unchanged, turbulence significantly enhances horizontal and vertical dispersion. The horizontal spread as a function of the level of turbulence and droplet properties is estimated. The conclusions from both studies are brought together and discussed in the context of the airborne spread of contaminants within a general hospital room.",,"['Eames, I.', 'Shoaib, D.', 'Klettner, C. A.', 'Taban, V.']",,,,
,PMC,Some aspects of the airborne transmission of infection,http://dx.doi.org/10.1098/rsif.2009.0236.focus,PMC2843950,,,"The relationship between the human body and the dissemination of potentially pathogenic particles and droplets is described. Airborne transmission of infection in operating theatres and a burns unit and the part played by the human microclimate and its interaction with ventilating air flows is discussed. The mechanisms by which different garment assemblies used for surgery can enhance particle dispersion are illustrated and the way that floor cleaning can increase the concentration of airborne organisms is described. The development of the successful use of ultra-clean air systems in orthopaedic implant surgery is reviewed. Relationships between contact and airborne transmission of disease are explored and ways by which containment strategies and metrics used in pharmaceutical and electronics manufacturing can be applied to the design and monitoring of healthcare areas is discussed. It is suggested that currently available techniques involving architectural, ventilation and operational aspects of healthcare provision, when properly applied, can markedly improve treatment outcomes that may otherwise be compromised by hospital-acquired infections involving both bacteria and viruses.",,"['Clark, Raymond P.', 'de Calcina-Goff, Mervyn L.']",,,,
,PMC,A schlieren optical study of the human cough with and without wearing masks for aerosol infection control,http://dx.doi.org/10.1098/rsif.2009.0295.focus,PMC2843945,,,"Various infectious agents are known to be transmitted naturally via respiratory aerosols produced by infected patients. Such aerosols may be produced during normal activities by breathing, talking, coughing and sneezing. The schlieren optical method, previously applied mostly in engineering and physics, can be effectively used here to visualize airflows around human subjects in such indoor situations, non-intrusively and without the need for either tracer gas or airborne particles. It accomplishes this by rendering visible the optical phase gradients owing to real-time changes in air temperature. In this study, schlieren video records are obtained of human volunteers coughing with and without wearing standard surgical and N95 masks. The object is to characterize the exhaled airflows and evaluate the effect of these commonly used masks on the fluid-dynamic mechanisms that spread infection by coughing. Further, a high-speed schlieren video of a single cough is analysed by a computerized method of tracking individual turbulent eddies, demonstrating the non-intrusive velocimetry of the expelled airflow. Results show that human coughing projects a rapid turbulent jet into the surrounding air, but that wearing a surgical or N95 mask thwarts this natural mechanism of transmitting airborne infection, either by blocking the formation of the jet (N95 mask), or by redirecting it in a less harmful direction (surgical mask).",,"['Tang, Julian W.', 'Liebner, Thomas J.', 'Craven, Brent A.', 'Settles, Gary S.']",,,,
,PMC,Exhaled droplets due to talking and coughing,http://dx.doi.org/10.1098/rsif.2009.0388.focus,PMC2843952,,,"Respiratory infections can be spread via ‘contact’ with droplets from expiratory activities such as talking, coughing and sneezing, and also from aerosol-generating clinical procedures. Droplet sizes predominately determine the times they can remain airborne, the possibility of spread of infectious diseases and thus the strategies for controlling the infections. While significant inconsistencies exist between the existing measured data on respiratory droplets generated during expiratory activities, a food dye was used in the mouth during measurements of large droplets, which made the expiratory activities ‘unnatural’. We carried out a series of experiments using glass slides and a microscope as well as an aerosol spectrometer to measure the number and size of respiratory droplets produced from the mouth of healthy individuals during talking and coughing with and without a food dye. The total mass of respiratory droplets was measured using a mask, plastic bag with tissue and an electronic balance with a high precision. Considerable subject variability was observed and the average size of droplets captured using glass slides and microscope was about 50–100 µm. Smaller droplets were also detected by the aerosol spectrometer. More droplets seemed to be generated when a food dye was used.",,"['Xie, Xiaojian', 'Li, Yuguo', 'Sun, Hequan', 'Liu, Li']",,,,
,PMC,Mathematical models for assessing the role of airflow on the risk of airborne infection in hospital wards,http://dx.doi.org/10.1098/rsif.2009.0305.focus,PMC2843948,,,"Understanding the risk of airborne transmission can provide important information for designing safe healthcare environments with an appropriate level of environmental control for mitigating risks. The most common approach for assessing risk is to use the Wells–Riley equation to relate infectious cases to human and environmental parameters. While it is a simple model that can yield valuable information, the model used as in its original presentation has a number of limitations. This paper reviews recent developments addressing some of the limitations including coupling with epidemic models to evaluate the wider impact of control measures on disease progression, linking with zonal ventilation or computational fluid dynamics simulations to deal with imperfect mixing in real environments and recent work on dose–response modelling to simulate the interaction between pathogens and the host. A stochastic version of the Wells–Riley model is presented that allows consideration of the effects of small populations relevant in healthcare settings and it is demonstrated how this can be linked to a simple zonal ventilation model to simulate the influence of proximity to an infector. The results show how neglecting the stochastic effects present in a real situation could underestimate the risk by 15 per cent or more and that the number and rate of new infections between connected spaces is strongly dependent on the airflow. Results also indicate the potential danger of using fully mixed models for future risk assessments, with quanta values derived from such cases less than half the actual source value.",,"['Noakes, Catherine J.', 'Sleigh, P. Andrew']",,,,
,PMC,Personalized ventilation as a control measure for airborne transmissible disease spread,http://dx.doi.org/10.1098/rsif.2009.0311.focus,PMC2843944,,,"The protective role of personalized ventilation (PV) against plausible airborne transmissible disease was investigated using cough droplets released from a ‘coughing machine’ simulating the human cough at different distances (1, 1.75 and 3 m) from the PV user. Particle image velocimetry was used to characterize and visualize the interaction between the cough-generated multiphase flow and PV-induced flow in the inhalation zone of the thermal breathing manikin. A dose–response model for unsteady imperfectly mixed environment was used to estimate the reduction in infection risk of two common diseases that can be transmitted by airborne mode. PV was able to both reduce the peak aerosol concentration levels and shorten the exposure time at all the examined injection distances. PV could reduce the infection risks of two diseases, influenza A and tuberculosis, by between 27 and 65 per cent. The protection offered by PV is less effective at a distance of 1.75 m than the other distances, as shown in the risk assessment results, as the PV-generated flow was blown off by the cough-generated flow for the longest time. Results of this study demonstrate the ability of desktop PV to mitigate the infection risk of airborne transmissible disease.",,"['Pantelic, Jovan', 'Sze-To, Gin Nam', 'Tham, Kwok Wai', 'Chao, Christopher Y. H.', 'Khoo, Yong Chuan Mike']",,,,
,PMC,Blood transfusion for the treatment of acute anaemia in inflammatory bowel disease and other digestive diseases,http://dx.doi.org/10.3748/wjg.15.4686,PMC2754517,,,"Allogeneic blood transfusion (ABT) is frequently used as the first therapeutic option for the treatment of acute anaemia in patients with inflammatory bowel disease (IBD), especially when it developed due to gastrointestinal or perioperative blood loss, but is not risk-free. Adverse effects of ABT include, but are not limited to, acute hemolytic reaction (wrong blood or wrong patient), febrile non-hemolytic transfusional reaction, bacterial contamination, transfusion-related acute lung injury, transfusion associated circulatory overload, transfusion-related immuno-modulation, and transmission of almost all infectious diseases (bacteria, virus, protozoa and prion), which might result in increased risk of morbidity and mortality. Unfortunately, the main physiological goal of ABT, i.e. to increase oxygen consumption by the hypoxic tissues, has not been well documented. In contrast, the ABT is usually misused only to increase the haemoglobin level within a fixed protocol [mostly two by two packed red blood cell (PRC) units] independently of the patient’s tolerance to normovolemic anaemia or his clinical response to the transfusion of PRC units according to a “one-by-one” administration schedule. Evidence-based clinical guidelines may promote best transfusion practices by implementing restrictive transfusion protocols, thus reducing variability and minimizing the avoidable risks of transfusion, and the use of autologous blood and pharmacologic alternatives. In this regard, preoperative autologous blood donation (PABD) consistently diminished the frequency of ABT, although its contribution to ABT avoidance is reduced when performed under a transfusion protocol. In addition, interpretation of utility of PABD in surgical IBD patients is hampered by scarcity of published data. However, the role of autologous red blood cells as drug carriers is promising. Finally, it must be stressed that a combination of methods used within well-constructed protocols will offer better prospects for blood conservation in selected IBD patients undergoing elective surgery.",,"['García-Erce, José Antonio', 'Gomollón, Fernando', 'Muñoz, Manuel']",,,,
,PMC,Development of a Test System To Evaluate Procedures for Decontamination of Respirators Containing Viral Droplets,http://dx.doi.org/10.1128/AEM.00799-09,PMC2786399,,,"The aim of this study was to develop a test system to evaluate the effectiveness of procedures for decontamination of respirators contaminated with viral droplets. MS2 coliphage was used as a surrogate for pathogenic viruses. A viral droplet test system was constructed, and the size distribution of viral droplets loaded directly onto respirators was characterized using an aerodynamic particle sizer. The sizes ranged from 0.5 to 15 μm, and the sizes of the majority of the droplets were the range from 0.74 to 3.5 μm. The results also showed that the droplet test system generated similar droplet concentrations (particle counts) at different respirator locations. The test system was validated by studying the relative efficiencies of decontamination of sodium hypochlorite (bleach) and UV irradiation with droplets containing MS2 virus on filtering facepiece respirators. It was hypothesized that more potent decontamination treatments would result in corresponding larger decreases in the number of viable viruses recovered from the respirators. Sodium hypochlorite doses of 2.75 to 5.50 mg/liter with a 10-min decontamination period resulted in approximately 3- to 4-log reductions in the level of MS2 coliphage. When higher sodium hypochlorite doses (≥8.25 mg/liter) were used with the same contact time that was used for the dilute solutions containing 2.75 to 5.50 mg/liter, all MS2 was inactivated. For UV decontamination at a wavelength of 254 nm, an approximately 3-log reduction in the level of MS2 virus was achieved with dose of 4.32 J/cm(2) (3 h of contact time with a UV intensity of 0.4 mW/cm(2)), while with higher doses of UV irradiation (≥7.20 J/cm(2); UV intensity, 0.4 mW/cm(2); contact times, ≥5 h), all MS2 was inactivated. These findings may lead to development of a standard method to test decontamination of respirators challenged by viral droplets.",,"['Vo, Evanly', 'Rengasamy, Samy', 'Shaffer, Ronald']",,,,
,PMC,"Complex Mosaic Composition of Near Full-Length Genomes of Two NED (NIH-ENVA-DOD) Subtype Panel HIV Type 1 Strains, BCF-Dioum and BCF-Kita, Originating from the Democratic Republic of Congo (DRC)",http://dx.doi.org/10.1089/aid.2009.0078,PMC2828238,,,"Sequence characterization of the near full-length genomes of HIV-1 isolates BCF-Dioum and BCF-Kita, originating from the Democratic Republic of Congo (DRC), was continued. These NED panel isolates, contributed by F. Brun-Vezinet (ENVA-France), were first identified as subtypes G and H, respectively. Our earlier analyses of portions of their pol genes showed that both were likely to be intersubtype recombinants of different composition. This study analyzed the remainder of each genome, confirming them to be complex recombinants. The BCF-Dioum genome resembles CRF06_cpx strains found in West Africa, composed of subtypes A/G/J/K. The BCF-Kita genome is a unique complex recombinant A–F–G–H–K–U strain. These data support previous observations of the complexity of strains originating from the DRC. BCF-Dioum may be a suitable strain for standards and reagents since it matches a defined circulating recombinant form. Studies and reagents made from BCF-Kita should take into account its complex genome.",,"['Huang, Diana D.', 'Foley, Brian T.', 'Tolzmann, Catlin A.', 'Ouma, Annastasia', 'Bremer, James W.']",,,,
,PMC,Pandemic Influenza Planning: Addressing the Needs of Children,http://dx.doi.org/10.2105/AJPH.2009.159970,PMC4504394,,,"Children represent one quarter of the US population. Because of its enormous size and special needs, it is critically important to address this population group in pandemic influenza planning. Here we describe the ways in which children are vulnerable in a pandemic, provide an overview of existing plans, summarize the resources available, and, given our experience with influenza A(H1N1), outline the evolving lessons we have learned with respect to planning for a severe influenza pandemic. We focus on a number of issues affecting children—vaccinations, medication availability, hospital capacity, and mental health concerns—and emphasize strategies that will protect children from exposure to the influenza virus, including infection control practices and activities in schools and child care programs.",,"['Stevenson, Elizabeth', 'Barrios, Lisa', 'Cordell, Ralph', 'Delozier, David', 'Gorman, Susan', 'Koenig, Linda J.', 'Odom, Erica', 'Polder, Jacquelyn', 'Randolph, Jean', 'Shimabukuro, Tom', 'Singleton, Christa']",,,,
,PMC,Pandemic Influenza and Pregnancy: An Opportunity to Reassess Maternal Bioethics,http://dx.doi.org/10.2105/AJPH.2008.140780,PMC4504390,,,"Large-scale infectious epidemics present the medical community with numerous medical and ethical challenges. Recent attention has focused on the likelihood of an impending influenza pandemic caused by the H5N1 virus. Pregnant women in particular present policymakers with great challenges to planning for such a public health emergency. By recognizing the specific considerations needed for this population, we can preemptively address the issues presented by infectious disease outbreaks. We reviewed the important ethical challenges presented by pregnant women and highlighted the considerations for all vulnerable groups when planning for a pandemic at both the local and the national level.",,"['Farrell, Ruth M.', 'Beigi, Richard H.']",,,,
,PMC,Pandemic Influenza Preparedness and Response Among Immigrants and Refugees,http://dx.doi.org/10.2105/AJPH.2008.154054,PMC4504387,,,"Some immigrants and refugees might be more vulnerable than other groups to pandemic influenza because of preexisting health and social disparities, migration history, and living conditions in the United States. Vulnerable populations and their service providers need information to overcome limited resources, inaccessible health services, limited English proficiency and foreign language barriers, cross-cultural misunderstanding, and inexperience applying recommended guidelines. To increase the utility of guidelines, we searched the literature, synthesized relevant findings, and examined their implications for vulnerable populations and stakeholders. Here we summarize advice from an expert panel of public health scientists and service program managers who attended a meeting convened by the Centers for Disease Control and Prevention, May 1 and 2, 2008, in Atlanta, Georgia.",,"['Truman, Benedict I.', 'Tinker, Timothy', 'Vaughan, Elaine', 'Kapella, Bryan K.', 'Brenden, Marta', 'Woznica, Celine V.', 'Rios, Elena', 'Lichtveld, Maureen']",,,,
,PMC,Preparing for and Responding to Pandemic Influenza: Implications for People With Disabilities,http://dx.doi.org/10.2105/AJPH.2009.162677,PMC4504380,,,"State, local, tribal, and territorial emergency managers and public health officials must address the specific needs of people with disabilities in their pandemic influenza plans. Evidence from Hurricane Katrina indicated that this population was disproportionately affected by the storm and aftermath. People with disabilities, particularly those who require personal assistance and those who reside in congregate care facilities, may be at increased risk during an influenza pandemic because of disrupted care or the introduction of the virus by their caregivers. Emergency and public health planners must ensure that personal assistance agencies and congregate care operators make provisions for backup staffing and that those who provide critical care are given adequate antiviral drugs and vaccines as they become available.",,"['Campbell, Vincent A.', 'Gilyard, Jamylle A.', 'Sinclair, Lisa', 'Sternberg, Tom', 'Kailes, June I.']",,,,
,PMC,Protecting Vulnerable Populations From Pandemic Influenza in the United States: A Strategic Imperative,http://dx.doi.org/10.2105/AJPH.2009.164814,PMC4504371,,,"Protecting vulnerable populations from pandemic influenza is a strategic imperative. The US national strategy for pandemic influenza preparedness and response assigns roles to governments, businesses, civic and community-based organizations, individuals, and families. Because influenza is highly contagious, inadequate preparedness or untimely response in vulnerable populations increases the risk of infection for the general population. Recent public health emergencies have reinforced the importance of preparedness and the challenges of effective response among vulnerable populations. We explore definitions and determinants of vulnerable, at-risk, and special populations and highlight approaches for ensuring that pandemic influenza preparedness includes these populations and enables them to respond appropriately. We also provide an overview of population-specific and cross-cutting articles in this theme issue on influenza preparedness for vulnerable populations.",,"['Hutchins, Sonja S.', 'Truman, Benedict I.', 'Merlin, Toby L.', 'Redd, Stephen C.']",,,,
,PMC,Pandemic Influenza and Community Preparedness,http://dx.doi.org/10.2105/AJPH.2008.153056,PMC4504368,,,"Objectives. We aimed to examine community knowledge about and attitudes toward the threat of pandemic influenza and assess the community acceptability of strategies to reduce its effect. Methods. We conducted computer-aided telephone interviews in 2007 with a cross-sectional sample of rural and metropolitan residents of South Australia. Results. Of 1975 households interviewed, half (50.2%) had never heard of pandemic influenza or were unaware of its meaning. Only 10% of respondents were extremely concerned about the threat of pandemic influenza. Respondents identified children as the highest priority for vaccination, if supplies were limited; they ranked politicians and teachers as the lowest priority. Although only 61.7% of respondents agreed with a policy of home isolation, 98.2% agreed if it was part of a national strategy. Respondents considered television to be the best means of educating the community. Conclusions. Community knowledge about pandemic influenza is poor despite widespread concern. Public education about pandemic influenza is essential if strategies to reduce the impact of the disease are to be effective.",,"['Marshall, Helen', 'Ryan, Philip', 'Roberton, Don', 'Street, Jackie', 'Watson, Maureen']",,,,
,PMC,Effective Health Risk Communication About Pandemic Influenza for Vulnerable Populations,http://dx.doi.org/10.2105/AJPH.2009.162537,PMC4504362,,,"The consequences of pandemic influenza for vulnerable populations will depend partly on the effectiveness of health risk communications. Strategic planning should fully consider how life circumstances, cultural values, and perspectives on risk influence behavior during a pandemic. We summarize recent scientific evidence on communication challenges and examine how sociocultural, economic, psychological, and health factors can jeopardize or facilitate public health interventions that require a cooperative public. If ignored, current communication gaps for vulnerable populations could result in unequal protection across society during an influenza pandemic. We offer insights on communication preparedness gleaned from scientific studies and the deliberations of public health experts at a meeting convened by the Centers for Disease Control and Prevention, May 1 and 2, 2008.",,"['Vaughan, Elaine', 'Tinker, Timothy']",,,,
,PMC,Pandemic Influenza and Pregnant Women: Summary of a Meeting of Experts,http://dx.doi.org/10.2105/AJPH.2008.152900,PMC4504360,,,"Pandemic Influenza: Special Considerations for Pregnant Women was a meeting convened by the Centers for Disease Control and Prevention in 2008 to obtain input from experts and key partners regarding clinical management of pregnant women and related public health actions to be taken during a pandemic. Meeting goals were to discuss issues specific to pregnant women, identify gaps in knowledge, and develop a public health approach for pregnant women in the event of a pandemic. The meeting focused on 4 main topics: prophylaxis and treatment with influenza antiviral and other medications, vaccine use, nonpharmaceutical interventions and health care planning, and communications. Participants reviewed the available evidence to guide action in each of these areas and identified areas of critical needs for future research.",,"['Rasmussen, Sonja A.', 'Jamieson, Denise J.', 'MacFarlane, Kitty', 'Cragan, Janet D.', 'Williams, Jennifer', 'Henderson, Zsakeba']",,,,
,PMC,The Open-Air Treatment of PANDEMIC INFLUENZA,http://dx.doi.org/10.2105/AJPH.2008.134627,PMC4504358,,,"The H1N1 “Spanish flu” outbreak of 1918–1919 was the most devastating pandemic on record, killing between 50 million and 100 million people. Should the next influenza pandemic prove equally virulent, there could be more than 300 million deaths globally. The conventional view is that little could have been done to prevent the H1N1 virus from spreading or to treat those infected; however, there is evidence to the contrary. Records from an “open-air” hospital in Boston, Massachusetts, suggest that some patients and staff were spared the worst of the outbreak. A combination of fresh air, sunlight, scrupulous standards of hygiene, and reusable face masks appears to have substantially reduced deaths among some patients and infections among medical staff. We argue that temporary hospitals should be a priority in emergency planning. Equally, other measures adopted during the 1918 pandemic merit more attention than they currently receive.",,"['Hobday, Richard A.', 'Cason, John W.']",,,,
,PMC,Protecting Home Health Care Workers: A Challenge to Pandemic Influenza Preparedness Planning,http://dx.doi.org/10.2105/AJPH.2008.157339,PMC4504355,,,"The home health care sector is a critical element in a pandemic influenza emergency response. Roughly 85% of the 1.5 million workers delivering in-home care to 7.6 million clients are low-wage paraprofessionals, mostly women, and disproportionately members of racial and ethnic minorities. Home health care workers' ability and willingness to respond during a pandemic depends on appropriate communication, training, and adequate protections, including influenza vaccination and respiratory protection. Preparedness planning should also include support for child care and transportation and help home health care workers protect their income and access to health care. We summarize findings from a national stakeholder meeting, which highlighted the need to integrate home health care employers, workers, community advocates, and labor unions into the planning process.",,"['Baron, Sherry', 'McPhaul, Kathleen', 'Phillips, Sally', 'Gershon, Robyn', 'Lipscomb, Jane']",,,,
,PMC,Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplant Recipients: A Global Perspective,http://dx.doi.org/10.1016/j.bbmt.2009.06.019,PMC3103296,,,,,"[None, 'Tomblyn, Marcie', 'Chiller, Tom', 'Einsele, Hermann', 'Gress, Ronald', 'Sepkowitz, Kent', 'Storek, Jan', 'Wingard, John R', 'Young, Jo-Anne H', 'Boeckh, Michael A']",,,,
,PMC,ACUTE RESPIRATORY DISTRESS SYNDROME: INSIGHTS GAINED FROM CLINICAL AND TRANSLATIONAL RESEARCH,,PMC5655174,,,"Acute lung injury and its more severe form acute respiratory distress syndrome (ARDS) are characterized by diffuse impairment of alveolocapillary membrane in the settings of different predisposing conditions such as sepsis, trauma and shock. Many intrahospital exposures, including aspiration, delayed resuscitation, high tidal volume mechanical ventilation and non critical use of transfusions may contribute or worsen ARDS. Therapy is targeted to treatment of predisposing condition, life supportive measures and prevention of nosocomial complications. Rigorous adherence to lung-protective mechanical ventilation is critical to prevent ventilator induced lung injury and decrease mortality. Although survival of ARDS patients has improved in the last decades ARDS mortality rates are still high and survivors encounter significant physical and psychological impairments.",,"['Kojicic, Marija', 'Festic, Emir', 'Gajic, Ognjen']",,,,
,PMC,Do FPs agree on what professionalism is?: NO,,PMC2762285,,,,,"Leong, Renata",,,,
,PMC,Prevalence of bovine viral diarrhea virus (BVDV) in persistently infected cattle and BVDV subtypes in affected cattle in beef herds in south central United States,,PMC2757709,,,"The prevalence of bovine viral diarrhea virus (BVDV) in persistently infected (PI) cattle in beef breeding herds was determined using 30 herds with 4530 calves. The samples were collected by ear notches and tested for BVDV antigens using immunohistochemistry (IHC) and antigen capture enzyme-linked immunosorbent assay (ACE). Animals with initial positives on both IHC and ACE were sampled again using both tests and serums were collected for viral propagation and sequencing of a viral genomic region, 5′-untranslated region (5′-UTR) for viral subtyping. Samples were also collected from the dams of PI calves. There were 25 PI calves from 4530 samples (0.55%) and these PI calves were from 5 of the 30 herds (16.7%). Two herds had multiple PI calves and 3 herds had only 1 PI calf. Only 1 of the 25 dams with a PI calf was also PI (4.0%). The subtype of all the PI isolates was BVDV1b. Histories of the ranches indicated 23 out of 30 had herd additions of untested breeding females. Twenty-four of the 30 herds had adult cowherd vaccinations against BVDV, primarily using killed BVDV vaccines at pregnancy examination.",,"['Fulton, Robert W.', 'Whitley, Evan M.', 'Johnson, Bill J.', 'Ridpath, Julia F.', 'Kapil, Sanjay', 'Burge, Lurinda J.', 'Cook, Billy J.', 'Confer, Anthony W.']",,,,
,PMC,Diagnosis and clinical signs of feline infectious peritonitis in the central nervous system,,PMC2748294,,,,,"['Diaz, José V.', 'Poma, Roberto']",,,,
,PMC,Infection for the acute physician,http://dx.doi.org/10.7861/clinmedicine.9-5-444,PMC4953453,,,,,"['Bewick, Thomas', 'Lim, Wei Shen']",,,,
,PMC,Basic Concepts of Microarrays and Potential Applications in Clinical Microbiology,http://dx.doi.org/10.1128/CMR.00019-09,PMC2772365,,,"Summary: The introduction of in vitro nucleic acid amplification techniques, led by real-time PCR, into the clinical microbiology laboratory has transformed the laboratory detection of viruses and select bacterial pathogens. However, the progression of the molecular diagnostic revolution currently relies on the ability to efficiently and accurately offer multiplex detection and characterization for a variety of infectious disease pathogens. Microarray analysis has the capability to offer robust multiplex detection but has just started to enter the diagnostic microbiology laboratory. Multiple microarray platforms exist, including printed double-stranded DNA and oligonucleotide arrays, in situ-synthesized arrays, high-density bead arrays, electronic microarrays, and suspension bead arrays. One aim of this paper is to review microarray technology, highlighting technical differences between them and each platform's advantages and disadvantages. Although the use of microarrays to generate gene expression data has become routine, applications pertinent to clinical microbiology continue to rapidly expand. This review highlights uses of microarray technology that impact diagnostic microbiology, including the detection and identification of pathogens, determination of antimicrobial resistance, epidemiological strain typing, and analysis of microbial infections using host genomic expression and polymorphism profiles.",,"['Miller, Melissa B.', 'Tang, Yi-Wei']",,,,
,PMC,Dengue Virus Pathogenesis: an Integrated View,http://dx.doi.org/10.1128/CMR.00035-09,PMC2772360,,,"Summary: Much remains to be learned about the pathogenesis of the different manifestations of dengue virus (DENV) infections in humans. They may range from subclinical infection to dengue fever, dengue hemorrhagic fever (DHF), and eventually dengue shock syndrome (DSS). As both cell tropism and tissue tropism of DENV are considered major determinants in the pathogenesis of dengue, there is a critical need for adequate tropism assays, animal models, and human autopsy data. More than 50 years of research on dengue has resulted in a host of literature, which strongly suggests that the pathogenesis of DHF and DSS involves viral virulence factors and detrimental host responses, collectively resulting in abnormal hemostasis and increased vascular permeability. Differential targeting of specific vascular beds is likely to trigger the localized vascular hyperpermeability underlying DSS. A personalized approach to the study of pathogenesis will elucidate the basis of individual risk for development of DHF and DSS as well as identify the genetic and environmental bases for differences in risk for development of severe disease.",,"['Martina, Byron E. E.', 'Koraka, Penelope', 'Osterhaus, Albert D. M. E.']",,,,
,PMC,Modern Uses of Electron Microscopy for Detection of Viruses,http://dx.doi.org/10.1128/CMR.00027-09,PMC2772359,,,"Summary: Electron microscopy, considered by some to be an old technique, is still on the forefront of both clinical viral diagnoses and viral ultrastructure and pathogenesis studies. In the diagnostic setting, it is particularly valuable in the surveillance of emerging diseases and potential bioterrorism viruses. In the research arena, modalities such as immunoelectron microscopy, cryo-electron microscopy, and electron tomography have demonstrated how viral structural components fit together, attach to cells, assimilate during replication, and associate with the cellular machinery during replication and egression. These studies provide information for treatment and vaccine strategies.",,"['Goldsmith, Cynthia S.', 'Miller, Sara E.']",,,,
,PMC,A duplex real-time RT-PCR assay for the detection of California serogroup and Cache Valley viruses,http://dx.doi.org/10.1016/j.diagmicrobio.2009.07.001,PMC2774246,,,"A duplex TaqMan real-time RT-PCR assay was developed for the detection of California (CAL) serogroup viruses and Cache Valley virus (CVV), for use in human surveillance. The targets selected for the assay were the sequences encoding the nucleocapsid protein of CAL and the G1 glycoprotein of CVV. Conserved regions were selected by aligning genetic sequences from various strains available in the GenBank database. Primers and probes were selected in conserved regions. The assay sensitivity was 75 gene copies (gc)/reaction for CAL serogroup viruses and 30 gc/reaction for CVV. The performance of the assay was linear over at least 6 log(10) gc. The assay was specific, given that it did not cross-react with a variety of pathogens. It did however, detect 11 viruses within the CAL serogroup, and 12 CVV isolates. The use of an internal control ensured that possible inefficiency in nucleic acid extraction or PCR inhibition would be detected.",,"['Wang, Heng', 'Nattanmai, Seela', 'Kramer, Laura D.', 'Bernard, Kristen A.', 'Tavakoli, Norma P.']",,,,
,PMC,Cellular Inflammatory Response to Flaviviruses in the Central Nervous System of a Primate Host,http://dx.doi.org/10.1369/jhc.2009.954180,PMC2746730,,,"Flaviviruses such as tick-borne encephalitis virus, Japanese encephalitis virus, West Nile virus, and St. Louis encephalitis virus are important neurotropic human pathogens, typically causing a devastating and often fatal neuroinfection. Flaviviruses induce neuroinflammation with typical features of viral encephalitides, including inflammatory cell infiltration, activation of microglia, and neuronal degeneration. Development of safe and effective live-virus vaccines against neurotropic flavivirus infections demands a detailed knowledge of their neuropathogenesis in a primate host that is evolutionarily close to humans. Here, we used computerized morphometric analysis to quantitatively assess the cellular inflammatory responses in the central nervous system (CNS) of rhesus monkeys infected with three antigenically divergent attenuated flaviviruses. The kinetics, spatial pattern, and magnitude of microglial activation, trafficking of T and B cells, and changes in T cell subsets within the CNS define unique phenotypic signatures for each of the three viruses. Our results provide a benchmark for investigation of cellular inflammatory responses induced by attenuated flaviviruses in the CNS of primate hosts and provide insight into the neuropathogenesis of flavivirus encephalitis that might guide the development of safe and effective live-virus vaccines. (J Histochem Cytochem 57:973–989, 2009)",,"['Maximova, Olga A.', 'Faucette, Lawrence J.', 'Ward, Jerrold M.', 'Murphy, Brian R.', 'Pletnev, Alexander G.']",,,,
,PMC,"The Safety of Flavocoxid, a Medical Food, in the Dietary Management of Knee Osteoarthritis",http://dx.doi.org/10.1089/jmf.2008.0244,PMC2784890,,,"This study was designed to determine the safety of a medical food, flavocoxid, a proprietary blend of free-B ring flavonoids and flavans from the root of Scutellaria baicalensis (Chinese skullcap) and the bark of Acacia catechu in the dietary management of knee osteoarthritis. The 12-week, randomized, double-blind, placebo-controlled trial in an academic medical center enrolled 59 patients with moderate osteoarthritis of at least one knee who were recruited who were classified as having “below average” to “a moderately above average cardiovascular risk” with a Framingham-based scoring tool. Subjects were randomized to flavocoxid 250 mg twice a day versus identical placebo. Safety measures, including recording of adverse events, incidence of serious adverse events, and results of routine laboratory values, were compared between the two groups. There were no major differences in the baseline demographic characteristics of the placebo and flavocoxid groups. With one exception no significant differences were found between the two groups with respect to adverse events by body system, blood pressure, or laboratory values. There was a significantly higher incidence of upper respiratory adverse events in the placebo group (35.4% vs. 5.8%, P = .0003). There were no intra- or inter-group differences in any of the laboratory parameters from study baseline to completion. Thus, flavocoxid is safe when used in a population with “below average” to “moderately above average cardiovascular risk” compared to placebo.",,"['Morgan, Sarah L.', 'Baggott, Joseph E.', 'Moreland, Larry', 'Desmond, Renee', 'Kendrach, Angela C.']",,,,
,PMC,Identification of Dengue-specific B-Cell Epitopes by Phage-display Random Peptide Library,,PMC3216131,,,"BACKGROUND: Dengue is the most important human viral disease transmitted by arthropod vectors. The availability of random peptide libraries (RPL) displayed on phage has provided a powerful tool for selecting sequences that mimic epitopes from microorganisms that are useful for diagnostic and vaccine development purposes. In this paper, we describe peptides that resemble the antigenic structure of B-cell epitopes of dengue virus identified from a phage-peptide library using human sera containing polyclonal antibodies against dengue virus. MATERIALS AND METHODS: Eighteen phage clones were isolated from the phage-display peptide library, J404, by affinity selection using human antisera against dengue virus type 3. These clones were tested for reactivity by ELISA with a panel of hyperimmune ascitic fluids (HAFs) containing antibodies either against all four dengue serotypes, West Nile virus (WNV) or Eastern equine encephalitis virus (EEEV) with control ascitic fluid (NAF) used as a negative control. RESULTS: Eight clones were recognized by HAFs against the four dengue serotypes, of which four significantly inhibited binding of anti-dengue antibodies to the virus. Two peptides with similar sequences to regions of NS3 and NS4B non-structural dengue virus proteins were identified. CONCLUSION: Our results suggest that these peptides could be used for the development of diagnostic tools for the detection of dengue virus infection and for a potential vaccine against this pathogen.",,"['Amin, Nevis', 'Aguilar, Alicia', 'Chamacho, Frank', 'Vázquez, Yaime', 'Pupo, Maritza', 'Ramirez, Juan Carlos', 'Izquierdo, Luis', 'Dafhnis, Felix', 'Stott, David Ian', 'Perez, Ela Maria', 'Acosta, Armando']",,,,
,PMC,The 3′ end of Turnip crinkle virus contains a highly interactive structure including a translational enhancer that is disrupted by binding to the RNA-dependent RNA polymerase,http://dx.doi.org/10.1261/rna.1708709,PMC2743042,,,"Precise temporal control is needed for RNA viral genomes to translate sufficient replication-required products before clearing ribosomes and initiating replication. A 3′ translational enhancer in Turnip crinkle virus (TCV) overlaps an internal T-shaped structure (TSS) that binds to 60S ribosomal subunits. The higher-order structure in the region was examined through alteration of critical sequences revealing novel interactions between an H-type pseudoknot and upstream residues, and between the TSS and internal and terminal loops of an upstream hairpin. Our results suggest that the TSS forms a stable scaffold that allows for simultaneous interactions with external sequences through base pairings on both sides of its large internal symmetrical loop. Binding of TCV RNA-dependent RNA polymerase (RdRp) to the region potentiates a widespread conformational shift with substantial rearrangement of the TSS region, including the element required for efficient ribosome binding. Degrading the RdRp caused the RNA to resume its original conformation, suggesting that the initial conformation is thermodynamically favored. These results suggest that the 3′ end of TCV folds into a compact, highly interactive structure allowing RdRp access to multiple elements including the 3′ end, which causes structural changes that potentiate the shift between translation and replication.",,"['Yuan, Xuefeng', 'Shi, Kerong', 'Meskauskas, Arturas', 'Simon, Anne E.']",,,,
,PMC,Role of Spike Protein Endodomains in Regulating Coronavirus Entry,http://dx.doi.org/10.1074/jbc.M109.043547,PMC2781689,,,"Enveloped viruses enter cells by viral glycoprotein-mediated binding to host cells and subsequent fusion of virus and host cell membranes. For the coronaviruses, viral spike (S) proteins execute these cell entry functions. The S proteins are set apart from other viral and cellular membrane fusion proteins by their extensively palmitoylated membrane-associated tails. Palmitate adducts are generally required for protein-mediated fusions, but their precise roles in the process are unclear. To obtain additional insights into the S-mediated membrane fusion process, we focused on these acylated carboxyl-terminal intravirion tails. Substituting alanines for the cysteines that are subject to palmitoylation had effects on both S incorporation into virions and S-mediated membrane fusions. In specifically dissecting the effects of endodomain mutations on the fusion process, we used antiviral heptad repeat peptides that bind only to folding intermediates in the S-mediated fusion process and found that mutants lacking three palmitoylated cysteines remained in transitional folding states nearly 10 times longer than native S proteins. This slower refolding was also reflected in the paucity of postfusion six-helix bundle configurations among the mutant S proteins. Viruses with fewer palmitoylated S protein cysteines entered cells slowly and had reduced specific infectivities. These findings indicate that lipid adducts anchoring S proteins into virus membranes are necessary for the rapid, productive S protein refolding events that culminate in membrane fusions. These studies reveal a previously unappreciated role for covalently attached lipids on the endodomains of viral proteins eliciting membrane fusion reactions.",,"['Shulla, Ana', 'Gallagher, Tom']",,,,
,PMC,Detection of Bocavirus in Saliva of Children with and without Respiratory Illness,http://dx.doi.org/10.1128/JCM.01508-09,PMC2786661,,,We evaluated saliva samples from 149 children 2 to 11 years old for human bocavirus (hBoV) DNA. hBoV was detected in saliva samples at asymptomatic enrollment in 3% (5/149) and during respiratory illness in 2% (2/106) of the cases. hBoV was detected in only 1/149 asymptomatic and 0/106 illness nasal samples.,,"['Martin, Emily T.', 'Taylor, James', 'Kuypers, Jane', 'Magaret, Amalia', 'Wald, Anna', 'Zerr, Danielle', 'Englund, Janet A.']",,,,
,PMC,De novo recruitment of antigen-experienced and naïve T cells contributes to the long term maintenance of anti-viral T cell populations in the persistently infected CNS,http://dx.doi.org/10.4049/jimmunol.0902164,PMC2811315,,,"Mice infected with attenuated strains of mouse hepatitis virus, strain JHM develop a chronic infection in the brain and spinal cord characterized by low levels of viral antigen persistence and retention of virus-specific CD4 and CD8 T cells at the site of infection. It is not known whether these cells are maintained by proliferation of T cells that entered the CNS during acute infection or are newly recruited from antigen-experienced or naïve T cell pools. Here, using adoptive transfer experiments and bone marrow chimeras, we show that at least some of these cells are recruited from the periphery, predominantly from the viral antigen-experienced T cell pool. Both virus-specific CD4 and CD8 T cells are functional, as assessed by cytokine expression and degranulation after peptide exposure. In addition, populations of virus-specific CD4 T cells undergo dynamic changes in the infected CNS, as previously shown for CD8 T cells, since ratios of cells responding to two CD4 T cell epitopes change by a factor of 5 during the course of persistence. Collectively, these results show that maintenance of T cell responses in the virus-infected CNS is a dynamic process. Further, virus-specific T cell numbers at this site of infection are maintained by recruitment from peripheral antigen-experienced and naïve T cell pools.",,"['Zhao, Jingxian', 'Zhao, Jincun', 'Perlman, Stanley']",,,,
,PMC,"Avian influenza virus, Streptococcus suis serotype 2, severe acute respiratory syndrome-coronavirus and beyond: molecular epidemiology, ecology and the situation in China",http://dx.doi.org/10.1098/rstb.2009.0093,PMC2865088,,,"The outbreak and spread of severe acute respiratory syndrome-associated coronavirus and the subsequent identification of its animal origin study have heightened the world's awareness of animal-borne or zoonotic pathogens. In addition to SARS, the highly pathogenic avian influenza virus (AIV), H5N1, and the lower pathogenicity H9N2 AIV have expanded their host ranges to infect human beings and other mammalian species as well as birds. Even the ‘well-known’ reservoir animals for influenza virus, migratory birds, became victims of the highly pathogenic H5N1 virus. Not only the viruses, but bacteria can also expand their host range: a new disease, streptococcal toxic shock syndrome, caused by human Streptococcus suis serotype 2 infection, has been observed in China with 52 human fatalities in two separate outbreaks (1998 and 2005, respectively). Additionally, enterohaemorrhagic Escherichia coli O157:H7 infection has increased worldwide with severe disease. Several outbreaks and sporadic isolations of this pathogen in China have made it an important target for disease control. A new highly pathogenic variant of porcine reproductive and respiratory syndrome virus (PRRSV) has been isolated in both China and Vietnam recently; although PRRSV is not a zoonotic human pathogen, its severe outbreaks have implications for food safety. All of these pathogens occur in Southeast Asia, including China, with severe consequences; therefore, we discuss the issues in this article by addressing the situation of the zoonotic threat in China.",,"['Ma, Ying', 'Feng, Youjun', 'Liu, Di', 'Gao, George F.']",,,,
,PMC,Livestock infectious diseases and zoonoses,http://dx.doi.org/10.1098/rstb.2009.0133,PMC2865087,,,"Infectious diseases of livestock are a major threat to global animal health and welfare and their effective control is crucial for agronomic health, for safeguarding and securing national and international food supplies and for alleviating rural poverty in developing countries. Some devastating livestock diseases are endemic in many parts of the world and threats from old and new pathogens continue to emerge, with changes to global climate, agricultural practices and demography presenting conditions that are especially favourable for the spread of arthropod-borne diseases into new geographical areas. Zoonotic infections that are transmissible either directly or indirectly between animals and humans are on the increase and pose significant additional threats to human health and the current pandemic status of new influenza A (H1N1) is a topical example of the challenge presented by zoonotic viruses. In this article, we provide a brief overview of some of the issues relating to infectious diseases of livestock, which will be discussed in more detail in the papers that follow.",,"['Tomley, Fiona M.', 'Shirley, Martin W.']",,,,
,PMC,Neglected and endemic zoonoses,http://dx.doi.org/10.1098/rstb.2009.0067,PMC2865085,,,"Endemic zoonoses are found throughout the developing world, wherever people live in close proximity to their animals, affecting not only the health of poor people but often also their livelihoods through the health of their livestock. Unlike newly emerging zoonoses that attract the attention of the developed world, these endemic zoonoses are by comparison neglected. This is, in part, a consequence of under-reporting, resulting in underestimation of their global burden, which in turn artificially downgrades their importance in the eyes of administrators and funding agencies. The development of cheap and effective vaccines is no guarantee that these endemic diseases will be eliminated in the near future. However, simply increasing awareness about their causes and how they may be prevented—often with very simple technologies—could reduce the incidence of many endemic zoonoses. Sustainable control of zoonoses is reliant on surveillance, but, as with other public-sector animal health services, this is rarely implemented in the developing world, not least because of the lack of sufficiently cheap diagnostics. Public–private partnerships have already provided advocacy for human disease control and could be equally effective in addressing endemic zoonoses.",,"['Maudlin, Ian', 'Eisler, Mark Charles', 'Welburn, Susan Christina']",,,,
,PMC,Critical Role of IL-17RA in Immunopathology of Influenza Infection,http://dx.doi.org/10.4049/jimmunol.0900995,PMC3638739,,,"Acute lung injury due to influenza infection is associated with high mortality, an increase in neutrophils in the airspace, and increases in tissue myeloperoxidase (MPO). Because IL-17A and IL-17F, ligands for IL-17 receptor antagonist (IL-17RA), have been shown to mediate neutrophil migration into the lung in response to LPS or Gram-negative bacterial pneumonia, we hypothesized that IL-17RA signaling was critical for acute lung injury in response to pulmonary influenza infection. IL-17RA was critical for weight loss and both neutrophil migration and increases in tissue myeloperoxidase (MPO) after influenza infection. However, IL-17RA was dispensable for the recruitment of CD8(+) T cells specific for influenza hemagglutinin or nucleocapsid protein. Consistent with this, IL-17RA was not required for viral clearance. However, in the setting of influenza infection, IL-17RA(−/−) mice showed significantly reduced levels of oxidized phospholipids, which have previously been shown to be an important mediator in several models of acute lung injury, including influenza infection and gastric acid aspiration. Taken together, these data support targeting IL-17 or IL-17RA in acute lung injury due to acute viral infection.",,"['Crowe, Christopher R.', 'Chen, Kong', 'Pociask, Derek A.', 'Alcorn, John F.', 'Krivich, Cameron', 'Enelow, Richard I.', 'Ross, Ted M.', 'Witztum, Joseph L.', 'Kolls, Jay K.']",,,,
,PMC,Microarray Analysis Identifies Changes in Inflammatory Gene Expression in Response to Amyloid-β Stimulation of Cultured Human Retinal Pigment Epithelial Cells,http://dx.doi.org/10.1167/iovs.09-3622,PMC3947389,,,"PURPOSE: Age-related macular degeneration (AMD) is a common cause of irreversible vision loss in the elderly. The hypothesis was that in vitro stimulation of RPE cells with Aβ(1-40), a constituent of drusen, promotes changes in gene expression and cellular pathways associated with the pathogenesis of AMD, including oxidative stress, inflammation, and angiogenesis. METHODS: Confluent human RPE cells were stimulated with Aβ(1-40), or the reverse peptide Aβ(40-1), and genome wide changes in gene expression were studied with gene microarrays. Selected genes were verified by qRT-PCR and ELISA. Pathway analysis with gene set enrichment analysis (GSEA) and ingenuity revealed top functional pathways in RPE after Aβ(1-40) stimulation. RESULTS: RPE cells stimulated with Aβ(1-40) (0.3 μM) for 24 hours resulted in 63 upregulated and 22 downregulated previously known genes. The upregulated genes were predominantly in inflammatory and immune response categories, but other categories were also represented, including apoptosis, cell signaling, cell proliferation, and signal transduction. Categories of downregulated genes included immune response, transporters, metabolic functions and transcription factors. ELISA confirmed that secreted levels of IL-8 were two times higher than control levels. GSEA and ingenuity analysis confirmed that the top affected pathways in RPE cells after Aβ(1-40) stimulation were inflammation and immune response related. Surprisingly, few angiogenic pathways were activated at the doses and exposure times studied. CONCLUSIONS: Aβ(1-40) promotes RPE gene expression changes in pathways associated with immune response, inflammation, and cytokine and interferon signaling pathways. Results may relate to in vivo mechanisms associated with the pathogenesis of AMD.",,"['Kurji, Khaliq H.', 'Cui, Jing Z.', 'Lin, Tony', 'Harriman, David', 'Prasad, Shiv S.', 'Kojic, Ljuba', 'Matsubara, Joanne A.']",,,,
,PMC,Coronavirus N protein N-terminal domain (NTD) specifically binds the transcriptional regulatory sequence (TRS) and melts TRS-cTRS RNA duplexes,http://dx.doi.org/10.1016/j.jmb.2009.09.040,PMC2783395,,,"All coronaviruses (CoVs), including the causative agent of severe acute respiratory syndrome (SARS), encode a nucleocapsid (N) protein that harbors two independent RNA binding domains of known structure, but poorly characterized RNA binding properties. We show here that the N-terminal domain (NTD) of N protein from mouse hepatitis virus (MHV), a virus most closely related to SARS-CoV, employs aromatic amino acid-nucleobase stacking interactions with a triple adenosine motif to mediate high-affinity binding to single-stranded RNAs containing the transcriptional regulatory sequence (TRS) or its complement (cTRS). Stoichiometric NTD fully unwinds a TRS-cTRS duplex that mimics a transiently formed transcription intermediate in viral subgenomic RNA synthesis. Mutation of the solvent-exposed Y127, positioned on the β-platform surface of our 1.75 Å structure, binds the TRS far less tightly and is severely crippled in its RNA unwinding activity. In contrast, the C-terminal domain (CTD) exhibits no RNA unwinding activity. Viruses harboring Y127A N mutation are strongly selected against and Y127A N does not support an accessory function in MHV replication. We propose that the helix melting activity of the coronavirus N protein NTD plays a critical accessory role in subgenomic RNA synthesis and other processes requiring RNA remodeling.",,"['Grossoehme, Nicholas E.', 'Li, Lichun', 'Keane, Sarah C.', 'Liu, Pinghua', 'Dann, Charles E.', 'Leibowitz, Julian L.', 'Giedroc, David P.']",,,,
,PMC,Cis-acting RNA elements in human and animal plus-strand RNA viruses,http://dx.doi.org/10.1016/j.bbagrm.2009.09.007,PMC2783963,,,"The RNA genomes of plus-strand RNA viruses have the ability to form secondary and higher-order structures that contribute to their stability and to their participation in inter- and intramolecular interactions. Those structures that are functionally important are called cis-acting RNA elements because their functions cannot be complemented in trans. They can be involved not only in RNA/RNA interactions but also in binding of viral and cellular proteins during the complex processes of translation, RNA replication and encapsidation. Most viral cis-acting RNA elements are located in the highly structured 5′- and 3′-nontranslated regions of the genomes but sometimes they also extend into the adjacent coding sequences. In addition, some cis-acting RNA elements are embedded within the coding sequences far away from the genomic ends. Although the functional importance of many of these structures have been confirmed by genetic and biochemical analyses their precise roles are not yet fully understood. In this review we have summarized what is known about cis-acting RNA elements in nine families of human and animal plus-strand RNA viruses with an emphasis on the most thoroughly characterized virus families, the Picornaviridae and Flaviviridae.",,"['Liu, Ying', 'Wimmer, Eckard', 'Paul, Aniko V.']",,,,
,PMC,Functional Analysis and Structural Modeling of Human APOBEC3G Reveal the Role of Evolutionarily Conserved Elements in the Inhibition of Human Immunodeficiency Virus Type 1 Infection and Alu Transposition,http://dx.doi.org/10.1128/JVI.01491-09,PMC2786736,,,"Retroelements are important evolutionary forces but can be deleterious if left uncontrolled. Members of the human APOBEC3 family of cytidine deaminases can inhibit a wide range of endogenous, as well as exogenous, retroelements. These enzymes are structurally organized in one or two domains comprising a zinc-coordinating motif. APOBEC3G contains two such domains, only the C terminal of which is endowed with editing activity, while its N-terminal counterpart binds RNA, promotes homo-oligomerization, and is necessary for packaging into human immunodeficiency virus type 1 (HIV-1) virions. Here, we performed a large-scale mutagenesis-based analysis of the APOBEC3G N terminus, testing mutants for (i) inhibition of vif-defective HIV-1 infection and Alu retrotransposition, (ii) RNA binding, and (iii) oligomerization. Furthermore, in the absence of structural information on this domain, we used homology modeling to examine the positions of functionally important residues and of residues found to be under positive selection by phylogenetic analyses of primate APOBEC3G genes. Our results reveal the importance of a predicted RNA binding dimerization interface both for packaging into HIV-1 virions and inhibition of both HIV-1 infection and Alu transposition. We further found that the HIV-1-blocking activity of APOBEC3G N-terminal mutants defective for packaging can be almost entirely rescued if their virion incorporation is forced by fusion with Vpr, indicating that the corresponding region of APOBEC3G plays little role in other aspects of its action against this pathogen. Interestingly, residues forming the APOBEC3G dimer interface are highly conserved, contrasting with the rapid evolution of two neighboring surface-exposed amino acid patches, one targeted by the Vif protein of primate lentiviruses and the other of yet-undefined function.",,"['Bulliard, Yannick', 'Turelli, Priscilla', 'Röhrig, Ute F.', 'Zoete, Vincent', 'Mangeat, Bastien', 'Michielin, Olivier', 'Trono, Didier']",,,,
,PMC,Inhibition of Protein Kinase R Activation and Upregulation of GADD34 Expression Play a Synergistic Role in Facilitating Coronavirus Replication by Maintaining De Novo Protein Synthesis in Virus-Infected Cells,http://dx.doi.org/10.1128/JVI.01546-09,PMC2786722,,,"A diversity of strategies is evolved by RNA viruses to manipulate the host translation machinery in order to create an optimal environment for viral replication and progeny production. One of the common viral targets is the α subunit of eukaryotic initiation factor 2 (eIF-2α). In this report, we show that phosphorylation of eIF-2α was severely suppressed in human and animal cells infected with the coronavirus infectious bronchitis virus (IBV). To understand whether this suppression is through inhibition of protein kinase R (PKR), the double-stranded-RNA-dependent kinase that is one of the main kinases responsible for phosphorylation of eIF-2α, cells infected with IBV were analyzed by Western blotting. The results showed that the level of phosphorylated PKR was greatly reduced in IBV-infected cells. Overexpression of IBV structural and nonstructural proteins (nsp) demonstrated that nsp2 is a weak PKR antagonist. Furthermore, GADD34, a component of the protein phosphatase 1 (PP1) complex, which dephosphorylates eIF-2α, was significantly induced in IBV-infected cells. Inhibition of the PP1 activity by okadaic acid and overexpression of GADD34, eIF-2α, and PKR, as well as their mutant constructs in virus-infected cells, showed that these viral regulatory strategies played a synergistic role in facilitating coronavirus replication. Taken together, these results confirm that IBV has developed a combination of two mechanisms, i.e., blocking PKR activation and inducing GADD34 expression, to maintain de novo protein synthesis in IBV-infected cells and, meanwhile, to enhance viral replication.",,"['Wang, Xiaoxing', 'Liao, Ying', 'Yap, Pei Ling', 'Png, Kim J.', 'Tam, James P.', 'Liu, Ding Xiang']",,,,
,PMC,Regulation of Proinflammatory Cytokine Expression in Primary Mouse Astrocytes by Coronavirus Infection,http://dx.doi.org/10.1128/JVI.01103-09,PMC2786718,,,"Previous studies have shown that proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), are differentially induced in primary mouse astrocytes by mouse hepatitis virus strain A59 (MHV-A59) and MHV-2. However, the signaling events that trigger TNF-α and IL-6 induction in these cells upon MHV infection remain unknown. In this study, we explored the potential signaling events. We found that induction of TNF-α and IL-6 occurred as early as 2 h postinfection and was completely dependent on viral replication. Using inhibitors specific for three mitogen-activated protein kinases, we showed that induction of TNF-α and IL-6 by MHV-A59 infection was mediated through activation of the Janus N-terminal kinase signaling pathway, but not through the extracellular signal-regulated kinase or p38 signaling pathway. This finding was further confirmed with knockdown experiments using small interfering RNAs specific for Janus N-terminal kinase. Interestingly, while nuclear factor κB (NF-κB), a key transcription factor required for the expression of proinflammatory cytokines in most cell types, was activated in astrocytes during MHV-A59 infection, disruption of the NF-κB pathway by peptide inhibitors did not significantly inhibit TNF-α and IL-6 expression. Furthermore, experiments using chimeric viruses demonstrated that the viral spike and nucleocapsid proteins, which play important roles in MHV pathogenicity in mice, are not responsible for the differential induction of the cytokines. These results illustrate the complexity of the regulatory mechanism by which MHV induces proinflammatory cytokines in primary astrocytes.",,"['Yu, Dongdong', 'Zhu, Hongqing', 'Liu, Yin', 'Cao, Jianzhong', 'Zhang, Xuming']",,,,
,PMC,The effect of environmental parameters on the survival of airborne infectious agents,http://dx.doi.org/10.1098/rsif.2009.0227.focus,PMC2843949,,,"The successful transmission of infection via the airborne route relies on several factors, including the survival of the airborne pathogen in the environment as it travels between susceptible hosts. This review summarizes the various environmental factors (particularly temperature and relative humidity) that may affect the airborne survival of viruses, bacteria and fungi, with the aim of highlighting specific aspects of environmental control that may eventually enhance the aerosol or airborne infection control of infectious disease transmission within hospitals.",,"Tang, Julian W.",,,,
,PMC,Physical interventions to interrupt or reduce the spread of respiratory viruses: systematic review,http://dx.doi.org/10.1136/bmj.b3675,PMC2749164,19773323,CC BY-NC,"Objective To review systematically the evidence of effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. Data sources Cochrane Library, Medline, OldMedline, Embase, and CINAHL, without restrictions on language or publication. Data selection Studies of any intervention to prevent the transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection, and hygiene). A search of study designs included randomised trials, cohort, case-control, crossover, before and after, and time series studies. After scanning of the titles, abstracts and full text articles as a first filter, a standardised form was used to assess the eligibility of the remainder. Risk of bias of randomised studies was assessed for generation of the allocation sequence, allocation concealment, blinding, and follow-up. Non-randomised studies were assessed for the presence of potential confounders and classified as being at low, medium, or high risk of bias. Data synthesis 58 papers of 59 studies were included. The quality of the studies was poor for all four randomised controlled trials and most cluster randomised controlled trials; the observational studies were of mixed quality. Meta-analysis of six case-control studies suggested that physical measures are highly effective in preventing the spread of severe acute respiratory syndrome: handwashing more than 10 times daily (odds ratio 0.45, 95% confidence interval 0.36 to 0.57; number needed to treat=4, 95% confidence interval 3.65 to 5.52), wearing masks (0.32, 0.25 to 0.40; NNT=6, 4.54 to 8.03), wearing N95 masks (0.09, 0.03 to 0.30; NNT=3, 2.37 to 4.06), wearing gloves (0.43, 0.29 to 0.65; NNT=5, 4.15 to 15.41), wearing gowns (0.23, 0.14 to 0.37; NNT=5, 3.37 to 7.12), and handwashing, masks, gloves, and gowns combined (0.09, 0.02 to 0.35; NNT=3, 2.66 to 4.97). The combination was also effective in interrupting the spread of influenza within households. The highest quality cluster randomised trials suggested that spread of respiratory viruses can be prevented by hygienic measures in younger children and within households. Evidence that the more uncomfortable and expensive N95 masks were superior to simple surgical masks was limited, but they caused skin irritation. The incremental effect of adding virucidals or antiseptics to normal handwashing to reduce respiratory disease remains uncertain. Global measures, such as screening at entry ports, were not properly evaluated. Evidence was limited for social distancing being effective, especially if related to risk of exposure—that is, the higher the risk the longer the distancing period. Conclusion Routine long term implementation of some of the measures to interrupt or reduce the spread of respiratory viruses might be difficult. However, many simple and low cost interventions reduce the transmission of epidemic respiratory viruses. More resources should be invested into studying which physical interventions are the most effective, flexible, and cost effective means of minimising the impact of acute respiratory tract infections.",2009 Sep 21,"['Jefferson, Tom', 'Del Mar, Chris', 'Dooley, Liz', 'Ferroni, Eliana', 'Al-Ansary, Lubna A', 'Bawazeer, Ghada A', 'van Driel, Mieke L', 'Foxlee, Ruth', 'Rivetti, Alessandro']",BMJ,,,
,PMC,Dynamics of SARS-Coronavirus HR2 Domain in the Prefusion and Transition States,http://dx.doi.org/10.1016/j.jmr.2009.09.012,PMC2794128,,,,,"['McReynolds, Susanna', 'Jiang, Shaokai', 'Rong, Lijun', 'Caffrey, Michael']",,,,
,PMC,Epidemiology and Clinical Presentations of Human Coronavirus NL63 Infections in Hong Kong Children,http://dx.doi.org/10.1128/JCM.00832-09,PMC2772645,,,"Human coronavirus NL63 (HCoV-NL63) has been found in children presenting with respiratory tract infections (RTIs). However, the epidemiology and clinical course of this newly identified virus have not been fully elucidated. This study investigated the epidemiology, seasonality, and clinical features of HCoV-NL63 in Hong Kong children. This study consisted of two cohorts of children hospitalized in a university-affiliated teaching hospital. In the 12-month retrospective part of the study, reverse transcription-PCR was used to detect HCoVs in nasopharyngeal aspirates (NPAs). Positive samples were sequenced to confirm the identity of the virus and to determine its phylogenetic relationship with the HCoV-NL63 strains found elsewhere. The second part covered a subsequent 12-month period in which patients were prospectively recruited. Altogether, 1,981 and 1,001 NPA specimens were studied in 2005-2006 and 2006-2007, respectively. Seventy-four (2.5%) HCoV isolates were identified and consisted of 17 (0.6%) HCoV-NL63 isolates, 37 (1.2%) HCoV-OC43 isolates, 14 (0.5%) HCoV-HKU1 isolates, and 6 (0.2%) HCoV-229E isolates. HCoV-NL63 infection was more common in 2006-2007 than 2005-2006 (1.2% and 0.3%, respectively; P = 0.006). From 2005 to 2007, the peak season for HCoV-NL63 infection was in September-October, which was earlier than the peak for HCoV-OC43 infections (December-January). HCoV-NL63-infected patients were younger and more likely to have croup, febrile convulsions, and acute gastroenteritis. The majority of local HCoV-NL63 isolates were phylogenetically closely related to those found in Belgium and The Netherlands. In conclusion, HCoV-NL63 is an important yet uncommon virus among our hospitalized children with acute RTIs.",,"['Leung, Ting Fan', 'Li, Chung Yi', 'Lam, Wai Yip', 'Wong, Gary W. K.', 'Cheuk, Edmund', 'Ip, Margaret', 'Ng, Pak Cheung', 'Chan, Paul K. S.']",,,,
,PMC,Mouse Hepatitis Virus Stem-Loop 2 Adopts a uYNMG(U)a-Like Tetraloop Structure That Is Highly Functionally Tolerant of Base Substitutions,http://dx.doi.org/10.1128/JVI.00915-09,PMC2786756,,,"Stem-loop 2 (SL2) of the 5′-untranslated region of the mouse hepatitis virus (MHV) contains a highly conserved pentaloop (C47-U48-U49-G50-U51) stacked on a 5-bp stem. Solution nuclear magnetic resonance experiments are consistent with a 5′-uYNMG(U)a or uCUYG(U)a tetraloop conformation characterized by an anti-C47-syn-G50 base-pairing interaction, with U51 flipped out into solution and G50 stacked on A52. Previous studies showed that U48C and U48A substitutions in MHV SL2 were lethal, while a U48G substitution was viable. Here, we characterize viruses harboring all remaining single-nucleotide substitutions in the pentaloop of MHV SL2 and also investigate the degree to which the sequence context of key pentaloop point mutations influences the MHV replication phenotype. U49 or U51 substitution mutants all are viable; C47 substitution mutants also are viable but produce slightly smaller plaques than wild-type virus. In contrast, G50A and G50C viruses are severely crippled and form much smaller plaques. Virus could not be recovered from G50U-containing mutants; rather, only true wild-type revertants or a virus, G50U/C47A, containing a second site mutation were recovered. These functional data suggest that the Watson-Crick edges of C47 and G50 (or A47 and U50 in the G50U/C47A mutant) are in close enough proximity to a hydrogen bond with U51 flipped out of the hairpin. Remarkably, increasing the helical stem stability rescues the previously lethal mutants U48C and G50U. These studies suggest that SL2 functions as an important, but rather plastic, structural element in stimulating subgenomic RNA synthesis in coronaviruses.",,"['Liu, Pinghua', 'Li, Lichun', 'Keane, Sarah C.', 'Yang, Dong', 'Leibowitz, Julian L.', 'Giedroc, David P.']",,,,
,PMC,Cell Cycle Arrest by Transforming Growth Factor β1 Enhances Replication of Respiratory Syncytial Virus in Lung Epithelial Cells,http://dx.doi.org/10.1128/JVI.00806-09,PMC2786720,,,"Respiratory syncytial virus (RSV) is a common respiratory viral infection in children which is associated with immune dysregulation and subsequent induction and exacerbations of asthma. We recently reported that treatment of primary human epithelial cells (PHBE cells) with transforming growth factor β (TGF-β) enhanced RSV replication. Here, we report that the enhancement of RSV replication is mediated by induction of cell cycle arrest. These data were confirmed by using pharmacologic inhibitors of cell cycle progression, which significantly enhanced RSV replication. Our data also showed that RSV infection alone resulted in cell cycle arrest in A549 and PHBE cells. Interestingly, our data showed that RSV infection induced the expression of TGF-β in epithelial cells. Blocking of TGF-β with anti-TGF-β antibody or use of a specific TGF-β receptor signaling inhibitor resulted in rescue of the RSV-induced cell cycle arrest, suggesting an autocrine mechanism. Collectively, our data demonstrate that RSV regulates the cell cycle through TGF-β in order to enhance its replication. These findings identify a novel pathway for upregulation of virus replication and suggest a plausible mechanism for association of RSV with immune dysregulation and asthma.",,"['Gibbs, John D.', 'Ornoff, Douglas M.', 'Igo, Heather A.', 'Zeng, Jennifer Y.', 'Imani, Farhad']",,,,
,PMC,Multifaceted Sequence-Dependent and -Independent Roles for Reovirus FAST Protein Cytoplasmic Tails in Fusion Pore Formation and Syncytiogenesis,http://dx.doi.org/10.1128/JVI.01667-09,PMC2786715,,,"Fusogenic reoviruses utilize the FAST proteins, a novel family of nonstructural viral membrane fusion proteins, to induce cell-cell fusion and syncytium formation. Unlike the paradigmatic enveloped virus fusion proteins, the FAST proteins position the majority of their mass within and internal to the membrane in which they reside, resulting in extended C-terminal cytoplasmic tails (CTs). Using tail truncations, we demonstrate that the last 8 residues of the 36-residue CT of the avian reovirus p10 FAST protein and the last 20 residues of the 68-residue CT of the reptilian reovirus p14 FAST protein enhance, but are not required for, pore expansion and syncytium formation. Further truncations indicate that the membrane-distal 12 residues of the p10 and 47 residues of the p14 CTs are essential for pore formation and that a residual tail of 21 to 24 residues that includes a conserved, membrane-proximal polybasic region present in all FAST proteins is insufficient to maintain FAST protein fusion activity. Unexpectedly, a reextension of the tail-truncated, nonfusogenic p10 and p14 constructs with scrambled versions of the deleted sequences restored pore formation and syncytiogenesis, while reextensions with heterologous sequences partially restored pore formation but failed to rescue syncytiogenesis. The membrane-distal regions of the FAST protein CTs therefore exert multiple effects on the membrane fusion reaction, serving in both sequence-dependent and sequence-independent manners as positive effectors of pore formation, pore expansion, and syncytiogenesis.",,"['Barry, Christopher', 'Duncan, Roy']",,,,
,PMC,A temperature sensitive mutant of heat shock protein 70 reveals an essential role during the early steps of tombusvirus replication,http://dx.doi.org/10.1016/j.virol.2009.08.003,PMC2776036,,,"By co-opting host proteins for their replication, plus-stranded RNA viruses can support robust replication and suppress host anti-viral responses. Tomato bushy stunt tombusvirus (TBSV) recruit the cellular heat shock protein 70 (Hsp70), an abundant cytosolic chaperone, into the replicase complex. By taking advantage of yeast model host, we demonstrate that the four-member SSA subfamily of HSP70 genes is essential for TBSV replication. The constitutively-expressed SSA1 and SSA2, which are resident proteins in the viral replicase, can be complemented by the heat-inducible SSA3 and/or SSA4 for TBSV replication. Using a yeast strain carrying a temperature sensitive ssa1(ts), but lacking functional SSA2/3/4, we show that inactivation of Ssa1p(ts) led to a defect in membrane localization of the viral replication proteins, resulting in cytosolic distribution of the viral proteins and lack of replicase activity. An in vitro replicase assembly assay with Ssa1p(ts) revealed that functional Ssa1p is required during the replicase assembly process, but not during minus- or plus-strand synthesis. Temperature shift experiments from nonpermissive to permissive in ssa1(ts) yeast revealed that the re-activated Ssa1p(ts) could promote efficient TBSV replication in the absence of other SSA genes. We also demonstrate that the purified recombinant Ssa3p can facilitate the in vitro assembly of the TBSV replicase on yeast membranes, demonstrating that Ssa3p can fully complement the function of Ssa1p. Taken together, the cytosolic SSA subfamily of Hsp70 proteins play essential and multiple roles in TBSV replication.",,"['Wang, Robert Yung-Liang', 'Stork, Jozsef', 'Pogany, Judit', 'Nagy, Peter D.']",,,,
,PMC,Germline-like predecessors of broadly neutralizing antibodies lack measurable binding to HIV-1 envelope glycoproteins: implications for evasion of immune responses and design of vaccine immunogens,http://dx.doi.org/10.1016/j.bbrc.2009.09.029,PMC2787893,,,"Several human monoclonal antibodies (hmAbs) including b12, 2G12 and 2F5 exhibit relatively potent and broad HIV-1 neutralizing activity. However, their elicitation in vivo by vaccine immunogens based on the HIV-1 envelope glycoprotein (Env) has not been successful. We have hypothesized that HIV-1 has evolved a strategy to reduce or eliminate the immunogenicity of the highly conserved epitopes of such antibodies by using “holes” (absence or very weak binding to these epitopes of germline antibodies that is not sufficient to initiate and/or maintain an efficient immune response) in the human germline B cell receptor (BCR) repertoire. To begin to test this hypothesis we have designed germline-like antibodies corresponding most closely to b12, 2G12 and 2F5 as well as to X5, m44 and m46 which are cross-reactive but with relatively weak neutralizing activity as natively occurring antibodies due to size and/or other effects. The germline-like X5, m44 and m46 bound with relatively high affinity to all tested Envs. In contrast, germline-like b12, 2G12 and 2F5 lacked measurable binding to Envs in an ELISA assay although the corresponding mature antibodies did. These results provide initial evidence that Env structures containing conserved vulnerable epitopes may not initiate humoral responses by binding to germline antibodies. Even if such responses are initiated by very weak binding undetectable in our assay it is likely that they will be outcompeted by responses to structures containing the epitopes of X5, m44, m46, and other antibodies that bind germline BCRs with much higher affinity/avidity. This hypothesis, if further supported by data, could contribute to our understanding of how HIV-1 evades immune responses and offer new concepts for design of effective vaccine immunogens.",,"['Xiao, Xiaodong', 'Chen, Weizao', 'Feng, Yang', 'Zhu, Zhongyu', 'Prabakaran, Ponraj', 'Wang, Yanping', 'Zhang, Mei-Yun', 'Longo, Nancy S.', 'Dimitrov, Dimiter S.']",,,,
,PMC,Lipidic Systems for In Vivo siRNA Delivery,http://dx.doi.org/10.1208/s12248-009-9140-1,PMC2782074,,,"The ability of small-interfering RNA (siRNA) to silence specific target genes not only offers a tool to study gene function but also represents a novel approach for the treatment of various human diseases. Its clinical use, however, has been severely hampered by the lack of delivery of these molecules to target cell populations in vivo due to their instability, inefficient cell entry, and poor pharmacokinetic profile. Various delivery vectors including liposomes, polymers, and nanoparticles have thus been developed in order to circumvent these problems. This review presents a comprehensive overview of the barriers and recent progress for both local and systemic delivery of therapeutic siRNA using lipidic vectors. Different strategies for formulating these siRNA-loaded lipid particles as well as the general concern about their safe use in vivo will also be discussed. Finally, current advances in the targeted delivery of siRNA and their impacts on the field of RNA interference (RNAi)-based therapy will be presented.",,"['Wu, Sherry Y.', 'McMillan, Nigel A. J.']",,,,
,PMC,Control of airborne infectious diseases in ventilated spaces,http://dx.doi.org/10.1098/rsif.2009.0228.focus,PMC2843946,,,"We protect ourselves from airborne cross-infection in the indoor environment by supplying fresh air to a room by natural or mechanical ventilation. The air is distributed in the room according to different principles: mixing ventilation, displacement ventilation, etc. A large amount of air is supplied to the room to ensure a dilution of airborne infection. Analyses of the flow in the room show that there are a number of parameters that play an important role in minimizing airborne cross-infection. The air flow rate to the room must be high, and the air distribution pattern can be designed to have high ventilation effectiveness. Furthermore, personalized ventilation may reduce the risk of cross-infection, and in some cases, it can also reduce the source of infection. Personalized ventilation can especially be used in hospital wards, aircraft cabins and, in general, where people are in fixed positions.",,"Nielsen, Peter V.",,,,
,PMC,"GBF1, a Guanine Nucleotide Exchange Factor for Arf, Is Crucial for Coxsackievirus B3 RNA Replication",http://dx.doi.org/10.1128/JVI.01244-09,PMC2772713,,,"The replication of enteroviruses is sensitive to brefeldin A (BFA), an inhibitor of endoplasmic reticulum-to-Golgi network transport that blocks activation of guanine exchange factors (GEFs) of the Arf GTPases. Mammalian cells contain three BFA-sensitive Arf GEFs: GBF1, BIG1, and BIG2. Here, we show that coxsackievirus B3 (CVB3) RNA replication is insensitive to BFA in MDCK cells, which contain a BFA-resistant GBF1 due to mutation M832L. Further evidence for a critical role of GBF1 stems from the observations that viral RNA replication is inhibited upon knockdown of GBF1 by RNA interference and that replication in the presence of BFA is rescued upon overexpression of active, but not inactive, GBF1. Overexpression of Arf proteins or Rab1B, a GTPase that induces GBF1 recruitment to membranes, failed to rescue RNA replication in the presence of BFA. Additionally, the importance of the interaction between enterovirus protein 3A and GBF1 for viral RNA replication was investigated. For this, the rescue from BFA inhibition of wild-type (wt) replicons and that of mutant replicons of both CVB3 and poliovirus (PV) carrying a 3A protein that is impaired in binding GBF1 were compared. The BFA-resistant GBF1-M832L protein efficiently rescued RNA replication of both wt and mutant CVB3 and PV replicons in the presence of BFA. However, another BFA-resistant GBF1 protein, GBF1-A795E, also efficiently rescued RNA replication of the wt replicons, but not that of mutant replicons, in the presence of BFA. In conclusion, this study identifies a critical role for GBF1 in CVB3 RNA replication, but the importance of the 3A-GBF1 interaction requires further study.",,"['Lanke, Kjerstin H. W.', 'van der Schaar, Hilde M.', 'Belov, George A.', 'Feng, Qian', 'Duijsings, Daniël', 'Jackson, Catherine L.', 'Ehrenfeld, Ellie', 'van Kuppeveld, Frank J. M.']",,,,
,PMC,The Roles of Chemokines in Rabies Virus Infection: Overexpression May Not Always Be Beneficial,http://dx.doi.org/10.1128/JVI.01346-09,PMC2772667,,,"It was found previously that induction of innate immunity, particularly chemokines, is an important mechanism of rabies virus (RABV) attenuation. To evaluate the effect of overexpression of chemokines on RABV infection, chemokines macrophage inflammatory protein 1α (MIP-1α), RANTES, and IP-10 were individually cloned into the genome of attenuated RABV strain HEP-Flury. These recombinant RABVs were characterized in vitro for growth properties and expression of chemokines. It was found that all the recombinant viruses grew as well as the parent virus, and each of the viruses expressed the intended chemokine in a dose-dependent manner. When these viruses were evaluated for pathogenicity in the mouse model, it was found that overexpression of MIP-1α further decreased RABV pathogenicity by inducing a transient innate immune response. In contrast, overexpression of RANTES or IP-10 increased RABV pathogenicity by causing neurological diseases, which is due to persistent and high-level expression of chemokines, excessive infiltration and accumulation of inflammatory cells in the central nervous system, and severe enhancement of blood-brain barrier permeability. These studies indicate that overexpression of chemokines, although important in controlling virus infection, may not always be beneficial to the host.",,"['Zhao, Ling', 'Toriumi, Harufusa', 'Kuang, Yi', 'Chen, Huanchun', 'Fu, Zhen F.']",,,,
,PMC,,,PMC2762764,20025201,CC BY,,2009 Sep 9,,PLoS Curr,,,
,PMC,Pandemic influenza communication: views from a deliberative forum,http://dx.doi.org/10.1111/j.1369-7625.2009.00562.x,PMC5060498,,,"Objective  To use a deliberative forum to elicit community perspectives on communication about pandemic influenza planning, and to compare these findings with the current Australian national communication strategy. Design  Deliberative forum of 12 persons randomly selected from urban South Australia. Forum members were briefed by experts in infection control, virology, ethics and public policy before deliberating on four key questions: what, how and when should the community be told about pandemic influenza and by whom? Results  The forum recommended provision of detailed and comprehensive information by credible experts, rather than politicians, using a variety of media including television and internet. Recommendations included cumulative communication to build expertise in the community, and specific strategies to include groups such as young people, people with physical or mental disabilities, and rural and remote communities. Information provided should be practical, accurate, and timely, with no ‘holding back’ about the seriousness of a pandemic. The forum expressed confidence in the expert witnesses, despite the acknowledged uncertainty of many of the predictions. Discussion and Conclusion  The deliberative forum’s recommendations were largely consistent with the Australian national pandemic influenza communication strategy and the relevant literature. However, the forum recommended: release of more detailed information than currently proposed in the national strategy; use of non‐political spokespersons; and use of novel communication methods. Their acceptance of uncertainty suggests that policy makers should be open about the limits of knowledge in potentially threatening situations. Our findings show that deliberative forums can provide community perspectives on topics such as communication about pandemic influenza.",,"['Rogers, Wendy A.', 'Street, Jackie M.', 'Braunack‐Mayer, Annette J.', 'Hiller, Janet E.', None]",,,,
,PMC,Genome-Wide Study of Pseudomonas aeruginosa Outer Membrane Protein Immunogenicity Using Self-Assembling Protein Microarrays,http://dx.doi.org/10.1128/IAI.00698-09,PMC2772540,,,"Pseudomonas aeruginosa is responsible for potentially life-threatening infections in individuals with compromised defense mechanisms and those with cystic fibrosis. P. aeruginosa infection is notable for the appearance of a humoral response to some known antigens, such as flagellin C, elastase, alkaline protease, and others. Although a number of immunogenic proteins are known, no effective vaccine has been approved yet. Here, we report a comprehensive study of all 262 outer membrane and exported P. aeruginosa PAO1 proteins by a modified protein microarray methodology called the nucleic acid-programmable protein array. From this study, it was possible to identify 12 proteins that trigger an adaptive immune response in cystic fibrosis and acutely infected patients, providing valuable information about which bacterial proteins are actually recognized by the immune system in vivo during the natural course of infection. The differential detections of these proteins in patients and controls proved to be statistically significant (P < 0.01). The study provides a list of potential candidates for the improvement of serological diagnostics and the development of vaccines.",,"['Montor, Wagner R.', 'Huang, Jin', 'Hu, Yanhui', 'Hainsworth, Eugenie', 'Lynch, Susan', 'Kronish, Jeannine-Weiner', 'Ordonez, Claudia L.', 'Logvinenko, Tanya', 'Lory, Stephen', 'LaBaer, Joshua']",,,,
,PMC,Quantitating T Cell Cross-Reactivity for Unrelated Peptide Antigens,http://dx.doi.org/10.4049/jimmunol.0901607,PMC2762195,,,"Quantitating the frequency of T cell cross-reactivity to unrelated peptides is essential to understanding T cell responses in infectious and autoimmune diseases. Here we used 15 mouse or human CD8(+) T cell clones (11 antiviral, 4 anti-self) in conjunction with a large library of defined synthetic peptides to examine nearly 30,000 TCR-peptide MHC class I interactions for cross-reactions. We identified a single cross-reaction consisting of an anti-self TCR recognizing a poxvirus peptide at relatively low sensitivity. We failed to identify any cross-reactions between the synthetic peptides in the panel and polyclonal CD8(+) T cells raised to viral or alloantigens. These findings provide the best estimate to date of the frequency of T cell cross-reactivity to unrelated peptides (∼1/30,000), explaining why cross-reactions between unrelated pathogens are infrequently encountered and providing a critical parameter for understanding the scope of self-tolerance.",,"['Ishizuka, Jeffrey', 'Grebe, Kristie', 'Shenderov, Eugene', 'Peters, Bjoern', 'Chen, Qiongyu', 'Peng, YanChun', 'Wang, Lili', 'Dong, Tao', 'Pasquetto, Valerie', 'Osroff, Carla', 'Sidney, John', 'Hickman, Heather', 'Cerundolo, Vincenzo', 'Sette, Alessandro', 'Bennink, Jack R.', 'McMchael, Andrew', 'Yewdell, Jonathan W.']",,,,
,PMC,Identification of Respiratory Viruses in Adults: Nasopharyngeal versus Oropharyngeal Sampling,http://dx.doi.org/10.1128/JCM.00886-09,PMC2772616,,,"The optimal method for identifying respiratory viruses in adults has not been established. The objective of the study was to compare the sensitivities of three sampling methods for this purpose. One thousand participants (mean age, 63.1 ± 17.8 years) were included. Of these, 550 were patients hospitalized for acute febrile lower respiratory tract infections and 450 were controls. Oropharyngeal swabs (OPS), nasopharyngeal swabs (NPS), and nasopharyngeal washings (NPW) were obtained from each participant and were tested for 12 respiratory viruses by a multiplex hydrolysis probes-based quantitative real-time reverse transcription-PCR. Patients were defined as positive for a specific virus if the virus was identified by at least one sampling method. In all, 251 viruses were identified in 244 participants. For the detection of any virus, the sensitivity rates for OPS, NPS, and NPW were 54.2%, 73.3%, and 84.9%, respectively (for OPS versus NPS and NPW, P < 0.00001; for NPS versus NPW, P < 0.003). Maximal sensitivity was obtained only with sampling by all three methods. The same gradation of sensitivity for the three sampling methods was found when influenza viruses, coronaviruses, and rhinoviruses were analyzed separately. The three sampling methods yielded equal sensitivity rates for respiratory syncytial virus. We conclude that nasopharyngeal sampling has a higher rate of sensitivity than oropharyngeal sampling and that the use of NPW has a higher rate of sensitivity than the use of NPS with a rigid cotton swab for the identification of respiratory viruses in adults. Sampling by all three methods is required for the maximal detection of respiratory viruses.",,"['Lieberman, David', 'Lieberman, Devora', 'Shimoni, Avi', 'Keren-Naus, Ayelet', 'Steinberg, Rachel', 'Shemer-Avni, Yonat']",,,,
,PMC,Design and Validation of Real-Time Reverse Transcription-PCR Assays for Detection of Pandemic (H1N1) 2009 Virus,http://dx.doi.org/10.1128/JCM.01103-09,PMC2772599,,,"Tracking novel influenza viruses which have the potential to cause pandemics, such as the pandemic (H1N1) 2009 virus, is a public health priority. Pandemic (H1N1) 2009 virus was first identified in Mexico in April 2009 and spread worldwide over a short period of time. Well-validated diagnostic tools that are rapid, sensitive, and specific for the detection and tracking of this virus are needed. Three real-time reverse transcription PCR (RT-PCR) assays for the amplification and detection of pandemic (H1N1) 2009 virus were developed, and their performance characteristics were compared with those of other published diagnostic assays. Thirty-nine samples confirmed to be positive for pandemic (H1N1) 2009 virus from Alberta, Canada, and six additional samples that were positive for influenza A virus but that were not typeable by using published seasonal influenza H1/H3 virus assays were available for this validation. Amplification and direct sequencing of the products was considered the “gold standard” for case identification. The new assays were sensitive and able to reproducibly detect virus in a 10(−6) dilution of 4 × 10(6) 50% tissue culture infective doses/ml when 5 μl was used as the template. They showed 100% specificity and did not cross-react with other respiratory viruses or seasonal influenza A virus subtypes. The coefficient of variation in crossing cycle threshold values for the detection of different template concentrations of pandemic (H1N1) 2009 virus was ≤3.13%, showing good reproducibility. The assays had a wide dynamic range for the detection of pandemic (H1N1) 2009 virus and utilized testing platforms appropriate for high diagnostic throughput with rapid turnaround times. We developed and validated these real-time PCR procedures with the goal that they will be useful for diagnosis and surveillance of pandemic (H1N1) 2009 virus. These findings will contribute to the informed management of this novel virus.",,"['Pabbaraju, Kanti', 'Wong, Sallene', 'Wong, Anita A.', 'Appleyard, Greg D.', 'Chui, Linda', 'Pang, Xiao-Li', 'Yanow, Stephanie K.', 'Fonseca, Kevin', 'Lee, Bonita E.', 'Fox, Julie D.', 'Preiksaitis, Jutta K.']",,,,
,PMC,Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Modulates Experimental Autoimmune Encephalomyelitis via an iNKT Cell-Dependent Mechanism,http://dx.doi.org/10.2353/ajpath.2009.090265,PMC2731130,,,"Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) is a CEA family member that has been reported to have an important role in the regulation of Th1-mediated colitis. In this study, we examined the role of CEACAM1 in an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Treatment of C57BL/6J mice with CEACAM1-Fc fusion protein, a homophilic ligand of CEACAM1, inhibited the severity of EAE and reduced myelin oligodendrocyte glycoprotein-derived peptide (MOG(35–55))-reactive interferon-γ and interleukin-17 production. In contrast, treatment of these animals with AgB10, an anti-mouse CEACAM1 blocking monoclonal antibody, generated increased severity of EAE in association with increased MOG(35–55)-specific induction of both interferon-γ and interleukin-17. These results indicated that the signal elicited through CEACAM1 ameliorated EAE disease severity. Furthermore, we found that there was both a rapid and enhanced expression of CEACAM1 on invariant natural killer T cells after activation. The effect of CEACAM1-Fc fusion protein and anti-CEACAM1 mAb on both EAE and MOG(35–55)-reactive cytokine responses were abolished in invariant natural killer T cell–deficient Jα18(−/−) mice. Taken together, the ligation of CEACAM1 negatively regulates the severity of EAE by reducing MOG(35–55)-specific induction of both interferon-γ and interleukin-17 via invariant natural killer T cell-dependent mechanisms.",,"['Fujita, Mayumi', 'Otsuka, Takao', 'Mizuno, Miho', 'Tomi, Chiharu', 'Yamamura, Takashi', 'Miyake, Sachiko']",,,,
,PMC,Diagnostics and Discovery in Viral Hemorrhagic Fevers,http://dx.doi.org/10.1111/j.1749-6632.2009.05056.x,PMC4109264,,,The rate of discovery of new microbes and of new associations of microbes with health and disease is accelerating. Many factors contribute to this phenomenon including those that favor the true emergence of new pathogens as well as new technologies and paradigms that enable their detection and characterization. This chapter reviews recent progress in the field of pathogen surveillance and discovery with a focus on viral hemorrhagic fevers.,,"['Lipkin, W. Ian', 'Palacios, Gustavo', 'Briese, Thomas']",,,,
,PMC,CXCL10 and trafficking of virus-specific T cells during coronavirus-induced demyelination,http://dx.doi.org/10.1080/08916930902810708,PMC2779158,,,"Chronic expression of CXC chemokine ligand 10 (CXCL10) in the central nervous system (CNS) following infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV) is associated with an immune-mediated demyelinating disease. Treatment of mice with anti-CXCL10 neutralizing antibody results in limited CD4+ T cell infiltration into the CNS accompanied by a reduction in white matter damage. The current study determines the antigen-specificity of the T lymphocytes present during chronic disease and evaluates how blocking CXCL10 signaling affects retention of virus-specific T cells within the CNS. CXCL10 neutralization selectively reduced accumulation and/or retention of virus-specific CD4+ T cells, yet exhibited limited effect on virus-specific CD8+ T cells. The response of CXCL10 neutralization on virus-specific T cell subsets is not due to differential expression of the CXCL10 receptor CXCR3 on T cells as there was no appreciable difference in receptor expression on virus-specific T cells during either acute or chronic disease. These findings emphasize the importance of virus-specific CD4+ T cells in amplifying demyelination in JHMV-infected mice. In addition, differential signals are required for trafficking and retention of virus-specific CD4+ and CD8+ T cells during chronic demyelination in JHMV-infected mice.",,"['Stiles, Linda N.', 'Liu, Michael T.', 'Kane, Joy A. C.', 'Lane, Thomas E.']",,,,
,PMC,Public Willingness to Take a Vaccine or Drug Under Emergency Use Authorization during the 2009 H1N1 Pandemic,http://dx.doi.org/10.1089/bsp.2009.0041,PMC2998968,,,"On April 26, 2009, the United States declared a public health emergency in response to a growing but uncertain threat from H1N1 influenza, or swine flu. In June, the World Health Organization declared a pandemic. In the U.S., hospitalizations due to swine flu numbered 6,506 on August 6, 2009, with 436 deaths; all 50 states have reported cases. The declaration of a public health emergency, followed by the approval of multiple Emergency Use Authorizations (EUAs) by the Food and Drug Administration, allowed the distribution of unapproved drugs or the off-label use of approved drugs to the public. Thus far, there are 2 antiviral medications available to the public as EUA drugs. It is possible that an H1N1 vaccine will be initially released as an EUA in the fall in the first large-scale use of the EUA mechanism. This study explores the public's willingness to use a drug or vaccine under the conditions stipulated in the FDA's nonbinding guidance regarding EUAs. Using Knowledge Networks' panel, we conducted an internet survey with 1,543 adults from a representative sample of the U.S. population with 2 oversamples of African Americans and Spanish-speaking Hispanics. Our completion rate was 62%. We examined willingness to accept an EUA drug or an H1N1 vaccine, the extent of worry associated with taking either, the conditions under which respondents would accept an EUA drug or vaccine, and the impact of language from the EUA fact sheets on people's willingness to accept a drug for themselves or their children. We also examined the association among these variables and race/ethnicity, education level, trust in government, previous vaccine acceptance, and perceived personal consequences from H1N1 influenza. These results provide critical insights into the challenges of communicating about EUA drugs and vaccine in our current pandemic.",,"['Quinn, Sandra Crouse', 'Kumar, Supriya', 'Freimuth, Vicki S.', 'Kidwell, Kelley', 'Musa, Donald']",,,,
,PMC,Research preparedness paves the way to respond to pandemic H1N1 2009 influenza virus,,PMC2770297,,,"The international community has been preparing for an influenza pandemic because of the threat posed by H5N1 avian influenza. Over the past several years, Canada has dedicated funding to boost capacity for research, and public health and health care system readiness and response in the event of a pandemic. The current H1N1/09 influenza pandemic is now testing our readiness. From a research perspective, the present commentary discusses how have we prepared, along with the research gaps. We conclude that: sources of pandemics are not always predictable; investment in the past few years has paid off in a rapid response to pandemic H1N1/09 virus in Canada; and research to meet the challenges of infectious diseases has to be done on an ongoing long-term basis, and its funding has to be flexible, available and predictable to maintain capacity and expertise. In addition, new vaccine technologies are needed to develop and produce vaccines for public health emergencies in a timely fashion.",,"['French, Michelle B', 'Loeb, Mark B', 'Richardson, Carol', 'Singh, Bhagirath']",,,,
,PMC,Quiz Corner,,PMC2726017,,,,,,,,,
,PMC,Vaccine Development in the Twenty-First Century: Changing Paradigms for Elusive Viruses,http://dx.doi.org/10.1038/clpt.2009.128,PMC2931821,,,,,"['Graham, BS', 'Ledgerwood, JE', 'Nabel, GJ']",,,,
,PMC,A synergistic interferon-γ production is induced by mouse hepatitis virus in interleukin-12 (IL-12)/IL-18-activated natural killer cells and modulated by carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1a receptor,http://dx.doi.org/10.1111/j.1365-2567.2008.03030.x,PMC2753941,,,"The production of interferon-γ (IFN-γ) by infiltrating natural killer (NK) cells in liver is involved in the control of mouse hepatitis virus (MHV) infection. The objectives of this study were to identify the mechanisms used by MHV type 3 to modulate the production of IFN-γ by NK cells during the acute hepatitis in susceptible C57BL/6 mice. Ex vivo and in vitro experiments revealed that NK cells, expressing carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1a (the MHV receptor), can produce a higher level of IFN-γ in the presence of both L2-MHV3 and interleukin-12 (IL-12)/IL-18. The synergistic production of IFN-γ by NK cells depends on viral replication rather than viral fixation only, because it is inhibited or not induced in cells infected with ultraviolet-inactivated viruses and in cells from Ceacam1a(−/−) mice infected with virulent viruses. The synergistic IFN-γ production involves the p38 mitogen-activated protein kinase (MAPK) rather than the extracellular signal-regulated kinase-1/2 MAPK signalling pathway. However, the signal triggered through the engagement of CEACAM1a decreases the production of IFN-γ, when these molecules are cross-linked using specific monoclonal antibodies. These results suggest that control of acute hepatitis by IFN-γ-producing NK cells may depend on both production of IL-12 and IL-18 in the liver environment and viral infection of NK cells.",,"['Jacques, Alexandre', 'Bleau, Christian', 'Turbide, Claire', 'Beauchemin, Nicole', 'Lamontagne, Lucie']",,,,
,PMC,Macrophage interleukin-6 and tumour necrosis factor-α are induced by coronavirus fixation to Toll-like receptor 2/heparan sulphate receptors but not carcinoembryonic cell adhesion antigen 1a,http://dx.doi.org/10.1111/j.1365-2567.2008.02946.x,PMC2753892,,,"A rapid antiviral immune response may be related to viral interaction with the host cell leading to activation of macrophages via pattern recognition receptors (PPRs) or specific viral receptors. Carcinoembryonic cell adhesion antigen 1a (CEACAM1a) is the specific receptor for the mouse hepatitis virus (MHV), a coronavirus known to induce acute viral hepatitis in mice. The objective of this study was to understand the mechanisms responsible for the secretion of high-pathogenic MHV3-induced inflammatory cytokines. We report that the induction of the pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor (TNF)-α in peritoneal macrophages does not depend on CEACAM1a, as demonstrated in cells isolated from Ceacam1a(−/−) mice. The induction of IL-6 and TNF-α production was related rather to the fixation of the spike (S) protein of MHV3 on Toll-like receptor 2 (TLR2) in regions enriched in heparan sulphate and did not rely on viral replication, as demonstrated with denatured S protein and UV-inactivated virus. High levels of IL-6 and TNF-α were produced in livers from infected C57BL/6 mice but not in livers from Tlr2(−/−) mice. The histopathological observations were correlated with the levels of those inflammatory cytokines. Depending on mouse strain, the viral fixation to heparan sulfate/TLR2 stimulated differently the p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB in the induction of IL-6 and TNF-α. These results suggest that TLR2 and heparan sulphate receptors can act as new viral PPRs involved in inflammatory responses.",,"['Jacques, Alexandre', 'Bleau, Christian', 'Turbide, Claire', 'Beauchemin, Nicole', 'Lamontagne, Lucie']",,,,
,PMC,Evidence from the Cochrane Collaboration for Traditional Chinese Medicine Therapies,http://dx.doi.org/10.1089/acm.2008.0414,PMC2856612,,,"BACKGROUND: The Cochrane Collaboration, an international not-for-profit organization that prepares and maintains systematic reviews of randomized trials of health care therapies, has produced reviews summarizing much of the evidence on Traditional Chinese Medicine (TCM). Our objective was to review the evidence base according to Cochrane systematic reviews. METHODS: In order to detect reviews focusing on TCM, we searched the titles and abstracts of all reviews in Issue 4, 2008 of the Cochrane Database of Systematic Reviews. For each review, we extracted data on the number of trials included and the total number of participants. We provided an indication of the strength of the review findings by assessing the reviewers' abstract conclusions statement. We supplemented our assessment of the abstract conclusions statements with a listing of the comparisons and outcomes showing statistically significant meta-analyses results. RESULTS: We identified 70 Cochrane systematic reviews of TCM, primarily acupuncture (n = 26) and Chinese herbal medicine (n = 42), and 1 each of moxibustion and t'ai chi. Nineteen (19) of 26 acupuncture reviews and 22/42 herbal medicine reviews concluded that there was not enough good quality trial evidence to make any conclusion about the efficacy of the evaluated treatment, while the remaining 7 acupuncture and 20 herbal medicine reviews and each of the moxibustion and t'ai chi reviews indicated a suggestion of benefit, which was qualified by a caveat about the poor quality and quantity of studies. Most reviews included many distinct interventions, controls, outcomes, and populations, and a large number of different comparisons were made, each with a distinct forest plot. CONCLUSIONS: Most Cochrane systematic reviews of TCM are inconclusive, due specifically to the poor methodology and heterogeneity of the studies reviewed. Some systematic reviews provide preliminary evidence of Chinese medicine's benefits to certain patient populations, underscoring the importance and appropriateness of further research. These preliminary findings should be considered tentative and need to be confirmed with rigorous randomized controlled trials.",,"['Manheimer, Eric', 'Wieland, Susan', 'Kimbrough, Elizabeth', 'Cheng, Ker', 'Berman, Brian M.']",,,,
,PMC,Interstrain Differences in the Development of Pyometra after Estrogen Treatment of Rats,,PMC2755022,,,"This case report describes the unanticipated development of pyometra in Brown Norway rats after treatment with estrogen. Sprague Dawley and Brown Norway rats were ovariectomized and randomly assigned to treatment groups (subcutaneous implantation of either a capsule containing 20 mg 17β-estradiol or an empty capsule, as a control). After irradiation of only the right eye, the rats were followed for several months in an attempt to determine the effects of estrogen on radiation cataractogenesis and investigate potential strain differences in this phenomenon. However, all Brown Norway rats that received estradiol treatment developed pyometra, whereas none the Sprague Dawley or control Brown Norway rats did. This case demonstrates the potential adverse effects of exogenous estrogen therapy, which are strain-specific in the rat. Caution should be taken when designing estrogen-related experiments involving Brown Norway rats and other potentially sensitive strains.",,"['Brossia, Lisa Jane', 'Roberts, Christopher Sean', 'Lopez, Jennifer T', 'Bigsby, Robert M', 'Dynlacht, Joseph R']",,,,
,PMC,Hospital design for better infection control,http://dx.doi.org/10.4103/0974-2700.55329,PMC2776365,20009307,CC BY,"The physical design and infrastructure of a hospital or institution is an essential component of its infection control measure. Thus is must be a prerequisite to take these into consideration from the initial conception and planning stages of the building. The balance between designing a hospital to be an open, accessible and public place and the control to reduce the spread of infections diseases is a necessity. At Singapore General Hospital, many lessons were learnt during the SARS outbreak pertaining to this. During and subsequent to the SARS outbreak, many changes evolved in the hospital to enable us to handle and face any emerging infectious situation with calm, confidence and the knowledge that staff and patients will be in good stead. This paper will share some of our experiences as well as challenges",2009 Sep-Dec,"Lateef, Fatimah",J Emerg Trauma Shock,,,
,PMC,N-Linked glycans on dengue viruses grown in mammalian and insect cells,http://dx.doi.org/10.1099/vir.0.012120-0,PMC2887570,,,"This study compared the ability of mosquito and mammalian cell-derived dengue virus (DENV) to infect human dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN)-expressing cells and characterized the structure of envelope (E) protein N-linked glycans on DENV derived from the two cell types. DENVs derived from both cell types were equally effective at infecting DC-SIGN-expressing human monocytes and dendritic cells. The N-linked glycans on mosquito cell-derived virus were a mix of high-mannose and paucimannose glycans. In virus derived from mammalian cells, the N-linked glycans were a mix of high-mannose and complex glycans. These results indicate that N-linked glycans are incompletely processed during DENV egress from cells, resulting in high-mannose glycans on viruses derived from both cell types. Studies with full-length and truncated E protein demonstrated that incomplete processing was most likely a result of the poor accessibility of glycans on the membrane-anchored protein.",,"['Hacker, Kari', 'White, Laura', 'de Silva, Aravinda M.']",,,,
,PMC,Rotavirus and Reovirus Modulation of the Interferon Response,http://dx.doi.org/10.1089/jir.2009.0072,PMC2956631,,,"The mammalian reoviruses and rotaviruses have evolved specific mechanisms to evade the Type I interferon (IFN) antiviral response. Rotavirus likely represses the IFN response by at least 4 mechanisms. First, the rotavirus protein NSP1, most likely functioning as an E3 ligase, can induce proteasome-dependent degradation of the transcription factors IRF3, IRF5, and IRF7 to prevent their induction of IFN. Second, NSP1 can induce proteasome-dependent degradation of the ubiquitin ligase complex protein β-TrCP, resulting in stabilization of IκB and concomitant failure of virus to activate NF-κB for induction of IFN. Third, rotavirus may sequester NF-κB in viroplasms. And fourth, rotavirus can prevent STAT1 and STAT2 nuclear translocation. The predominant mechanism for rotavirus inhibition of the IFN response is likely both rotavirus strain-specific and cell type-specific. The mammalian reoviruses also display strain-specific differences in their modulation of the IFN response. Reovirus activates RIG-I and IPS-1 for phosphorylation of IRF3. Reovirus-induced activation of MDA5 also participates in induction if IFN-β, perhaps through activation of NF-κB. Reovirus likely inhibits the IFN response by at least 3 virus strain-specific mechanisms. First, the reovirus μ2 protein can induce an unusual nuclear accumulation of IRF9 and repress IFN-stimulated gene (ISG) expression, most likely by disrupting IRF9 function as part of the heterotrimeric transcription factor complex, ISGF3. Second, the reovirus σ3 protein can bind dsRNA and prevent activation of the latent antiviral effector protein PKR. And third, genetic approaches have identified the reovirus λ2 and σ2 proteins in virus strain-specific modulation of the IFN response, but the significance remains unclear. In sum, members of the family Reoviridae have evolved a variety of mechanisms to subvert the host's innate protective response.",,"Sherry, Barbara",,,,
,PMC,Detection of Four Human Coronaviruses in Respiratory Infections in Children: A One-Year Study in Colorado,http://dx.doi.org/10.1002/jmv.21541,PMC2879166,,,"Lower respiratory tract infections are the leading cause of death in children worldwide. Studies on the epidemiology and clinical associations of the four human non-SARS human coronaviruses (HCoVs) using sensitive polymerase chain reaction (PCR) assays are needed to evaluate the clinical significance of HCoV infections worldwide. Pediatric respiratory specimens (1,683) submitted to a diagnostic virology laboratory over a 1-year period (December 2004–November 2005) that were negative for seven respiratory viruses by conventional methods were tested for RNA of four HCoVs using sensitive RT-PCR assays. Coronavirus RNAs were detected in 84 (5.0%) specimens: HCoV-NL63 in 37 specimens, HCoV-OC43 in 34, HCoV-229E in 11, and HCoV-HKU1 in 2. The majority of HCoV infections occurred during winter months, and over 62% were in previously healthy children. Twenty-six (41%) coronavirus positive patients had evidence of a lower respiratory tract infection (LRTI), 17 (26%) presented with vomiting and/or diarrhea, and 5 (8%) presented with meningoencephalitis or seizures. Respiratory specimens from one immunocompromised patient were persistently positive for HCoV-229E RNA for 3 months. HCoV-NL63-positive patients were nearly twice as likely to be hospitalized (P = 0.02) and to have a LRTI (P = 0.04) than HCoV-OC43-positive patients. HCoVs are associated with a small, but significant number (at least 2.4% of total samples submitted), of both upper and lower respiratory tract illnesses in children in Colorado. Our data raise the possibility that HCoV may play a role in gastrointestinal and CNS disease. Additional studies are needed to investigate the potential roles of HCoVs in these diseases.",,"['Dominguez, Samuel R.', 'Robinson, Christine C.', 'Holmes, Kathryn V.']",,,,
,PMC,Effects of Moisture Content on the Storage Stability of Dried Lipoplex Formulations,http://dx.doi.org/10.1002/jps.21846,PMC2785107,,,"The purpose of this study is to investigate the effects of moisture content on the storage stability of freeze-dried lipoplex formulations. DC-Cholesterol: DOPE (dioleoyl phosphatidylethanolamine) /plasmid DNA lipoplexes were prepared at a 3-to-2 DC-Cholesterol(+) to DNA(−) molar ratio and lyophilized prior to storing at room temperature, 40 °C, and 60 °C for three months. Different residual moistures (1.93%, 1.10%, 1.06% and 0.36%) were obtained by altering the secondary drying temperatures. In addition to moisture content, lipoplex formulations were evaluated after freeze-drying and/ or storage for particle size, transfection efficiency, accumulation of TBARS (thiobarbituric reactive substances), glass transition temperature, DNA supercoil content, and surface area. Lipoplex formulations stored at room temperature for 3 months maintain TBARS concentrations and supercoil contents. At higher storage temperatures, formulations possessing the highest moisture content (1.93%) maintained significantly lower TBARS concentrations and higher supercoil content than those with the lowest (0.36%) moisture content. Curiously, the intermediate moisture contents exhibited marked differences in stability despite virtually identical moisture contents. Subsequent measurements of surface area indicated that the lower stability corresponded to higher surface area in the dried cake, suggesting that there may be an interplay between water content and surface area that contributes to storage stability.",,"['Yu, Jinxiang', 'Anchordoquy, Thomas J.']",,,,
,PMC,Synergistic Effects of Surfactants and Sugars on Lipoplex Stability During Freeze-drying and Rehydration,http://dx.doi.org/10.1002/jps.21564,PMC2721014,,,"The stability of non-viral vectors during freeze-drying has been well-studied, and it has been established that sugars can protect lipoplexes during freeze-drying. However low levels of damage are often observed after freeze-drying, and this damage is more evident in dilute lipoplex preparations. By investigating the stability of lipoplexes after each step in the freeze-drying cycle (i.e., freezing, primary drying, and secondary drying) we strive to understand the mechanisms responsible for damage and identify improved stabilization strategies. N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP)-cholesterol/plasmid DNA lipoplexes were prepared at an equimolar DOTAP to cholesterol ratio, and a 3-to-1 DOTAP(+) to DNA(−) charge ratio. Our experiments indicate that despite sufficient levels of “stabilizing” sugars, significant damage is still evident when dilute lipoplex preparations are subjected to freeze-drying. Analysis of the different stages of freeze-drying suggests that significant damage occurs during freezing, and that sugars have a limited capacity to protect against this freezing-induced damage. Similar effects have been observed in studies with proteins, and surfactants have been employed in protein formulations to protect against surface-induced damage, e.g., at the ice crystal, solid, air or sugar glass surfaces. However, the use of surfactants in a lipid-based formulation is inherently risky due to the potential for altering/solubilizing the lipid delivery vehicle. Our data indicate that judicious use of surfactants can reduce surface-induced damage, and result in better preservation of lipoplex size and transfection activity after freeze-drying.",,"['Yu, Jinxiang', 'Anchordoquy, Thomas J.']",,,,
,PMC,Early Upregulation of Acute Respiratory Distress Syndrome-Associated Cytokines Promotes Lethal Disease in an Aged-Mouse Model of Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/JVI.01322-09,PMC2738172,,,,,"['Rockx, Barry', 'Baas, Tracey', 'Zornetzer, Gregory A.', 'Haagmans, Bart', 'Sheahan, Timothy', 'Frieman, Matthew', 'Dyer, Matthew D.', 'Teal, Thomas H.', 'Proll, Sean', 'van den Brand, Judith', 'Baric, Ralph', 'Katze, Michael G.']",,,,
,PMC,Activation of Transgene-specific T Cells Following Lentivirus-mediated Gene Delivery to Mouse Lung,http://dx.doi.org/10.1038/mt.2009.190,PMC2839217,,,"Integrating lentiviral vectors based on the human immunodeficiency virus type-1 (HIV-1) can transduce quiescent cells, which in lung account for almost 95% of the epithelial cell population. Pseudotyping lentiviral vectors with the envelope glycoprotein from the Ebola Zaire virus, the lymphocytic choriomeningitis virus (LCMV), the Mokola virus, and the vesicular stomatitis virus (VSV-G) resulted in transduction of mouse alveolar epithelium, but gene expression in the lung of C57BL/6 and BALB/c mice waned within 90 days of vector injection. Intratracheal delivery of the four pseudotyped lentiviral vectors resulted in transgene-specific T-cell activation in both mouse strains, albeit lower than that achieved by intramuscular injection of the vectors. We performed an adoptive transfer of luciferase-specific T cells, isolated from spleen or lung of donor mice injected with VSV-G-pseudotyped lentivirus vector expressing luciferase into the muscle or lung, respectively, into recipient recombination-activating gene (RAG)–deficient mice transduced in lung with adenovirus expressing firefly luciferase (ffluc2). Gene expression declined within 7 days of adoptive transfer approaching background levels by day 36. Taken together, our results suggest that the loss of transduced cells in lung is due to VSV-G.HIV vector–mediated activation of transgene-specific T cells rather than as result of normal turnover of airway cells.",,"['Limberis, Maria P', 'Bell, Christie L', 'Heath, Jack', 'Wilson, James M']",,,,
,PMC,Footprinting analysis of BWYV pseudoknot–ribosome complexes,http://dx.doi.org/10.1261/rna.1385409,PMC2743054,,,"Many viruses regulate translation of polycistronic mRNA using a −1 ribosomal frameshift induced by an RNA pseudoknot. When the ribosome encounters the pseudoknot barrier that resists unraveling, transient mRNA–tRNA dissociation at the decoding site, results in a shift of the reading frame. The eukaryotic frameshifting pseudoknot from the beet western yellow virus (BWYV) has been well characterized, both structurally and functionally. Here, we show that in order to obtain eukaryotic levels of frameshifting efficiencies using prokaryotic Escherichia coli ribosomes, which depend upon the structural integrity of the BWYV pseudoknot, it is necessary to shorten the mRNA spacer between the slippery sequence and the pseudoknot by 1 or 2 nucleotides (nt). Shortening of the spacer is likely to re-establish tension and/or ribosomal contacts that were otherwise lost with the smaller E. coli ribosomes. Chemical probing experiments for frameshifting and nonframeshifting BWYV constructs were performed to investigate the structural integrity of the pseudoknot confined locally at the mRNA entry site. These data, obtained in the pretranslocation state, show a compact overall pseudoknot structure, with changes in the conformation of nucleotides (i.e., increase in reactivity to chemical probes) that are first “hit” by the ribosomal helicase center. Interestingly, with the 1-nt shortened spacer, this increase of reactivity extends to a downstream nucleotide in the first base pair (bp) of stem 1, consistent with melting of this base pair. Thus, the 3 bp that will unfold upon translocation are different in both constructs with likely consequences on unfolding kinetics.",,"['Mazauric, Marie-Hélène', 'Leroy, Jean-Louis', 'Visscher, Koen', 'Yoshizawa, Satoko', 'Fourmy, Dominique']",,,,
,PMC,Structural basis for ligand and substrate recognition by torovirus hemagglutinin esterases,http://dx.doi.org/10.1073/pnas.0904266106,PMC2747215,,,"Hemagglutinin esterases (HEs), closely related envelope glycoproteins in influenza C and corona- and toroviruses, mediate reversible attachment to O-acetylated sialic acids (Sias). They do so by acting both as lectins and as receptor-destroying enzymes, functions exerted by separate protein domains. HE divergence was accompanied by changes in quaternary structure and in receptor and substrate specificity. The selective forces underlying HE diversity and the molecular basis for Sia specificity are poorly understood. Here we present crystal structures of porcine and bovine torovirus HEs in complex with receptor analogs. Torovirus HEs form homodimers with sialate-O-acetylesterase domains almost identical to corresponding domains in orthomyxo- and coronavirus HEs, but with unique lectin sites. Structure-guided biochemical analysis of the esterase domains revealed that a functionally, but not structurally conserved arginine–Sia carboxylate interaction is critical for the binding and positioning of glycosidically bound Sias in the catalytic pocket. Although essential for efficient de-O-acetylation of Sias, this interaction is not required for catalysis nor does it affect substrate specificity. In fact, the distinct preference of the porcine torovirus enzyme for 9-mono- over 7,9-di-O-acetylated Sias can be explained from a single-residue difference with HEs of more promiscuous specificity. Apparently, esterase and lectin pockets coevolved; also the porcine torovirus HE receptor-binding site seems to have been designed to use 9-mono- and exclude di-O-acetylated Sias, possibly as an adaptation to replication in swine. Our findings shed light on HE evolution and provide fundamental insight into mechanisms of substrate binding, substrate recognition, and receptor selection in this important class of virion proteins.",,"['Langereis, Martijn A.', 'Zeng, Qinghong', 'Gerwig, Gerrit J.', 'Frey, Barbara', 'von Itzstein, Mark', 'Kamerling, Johannis P.', 'de Groot, Raoul J.', 'Huizinga, Eric G.']",,,,
,PMC,SARS-coronavirus spike S2 domain flanked by cysteine residues C822 and C833 is important for activation of membrane fusion,http://dx.doi.org/10.1016/j.virol.2009.07.038,PMC3594805,,,"The S2 domain of the coronavirus spike (S) protein is known to be responsible for mediating membrane fusion. In addition to a well-recognized cleavage site at the S1–S2 boundary, a second proteolytic cleavage site has been identified in the severe acute respiratory syndrome coronavirus (SARS-CoV) S2 domain (R797). C terminal to this S2 cleavage site is a conserved region flanked by cysteine residues C822 and C833. Here, we investigated the importance of this well conserved region for SARS-CoV S-mediated fusion activation. We show that the residues between C822-C833 are well conserved across all coronaviruses. Mutagenic analysis of SARS-CoV S, combined with cell–cell fusion and pseudotyped virion infectivity assays, showed a critical role for the core-conserved residues C822, D830, L831, and C833. Based on available predictive models, we propose that the conserved domain flanked by cysteines 822 and 833 forms a loop structure that interacts with components of the SARS-CoV S trimer to control the activation of membrane fusion.",,"['Madu, Ikenna G.', 'Belouzard, Sandrine', 'Whittaker, Gary R.']",,,,
,PMC,"Rat alveolar type I cells proliferate, express OCT-4, and exhibit phenotypic plasticity in vitro",http://dx.doi.org/10.1152/ajplung.90389.2008,PMC2793185,,,"Alveolar type I (TI) cells are large, squamous cells that cover 95–99% of the internal surface area of the lung. Although TI cells are believed to be terminally differentiated, incapable of either proliferation or phenotypic plasticity, TI cells in vitro both proliferate and express phenotypic markers of other differentiated cell types. Rat TI cells isolated in purities of >99% proliferate in culture, with a sixfold increase in cell number before the cells reach confluence; >50% of the cultured TI cells are Ki67+. At cell densities of 1–2 cells/well, ∼50% of the cells had the capacity to form colonies. Under the same conditions, type II cells do not proliferate. Cultured TI cells express RTI40 and aquaporin 5, phenotypic markers of the TI cell phenotype. By immunofluorescence, Western blotting, and Q-PCR, TI cells express OCT-4A (POU5F1), a transcription factor associated with maintenance of the pluripotent state in stem cells. Based on the expression patterns of various marker proteins, TI cells are distinct from either of two recently described putative pulmonary multipotent cell populations, the bronchoalveolar stem cell or the OCT-4+ stem/progenitor cell. Although TI cells in adult rat lung tissue do not express either surfactant protein C (SP-C) or CC10, respective markers of the TII and Clara cell phenotypes, in culture TI cells can be induced to express both SP-C and CC10. Together, the findings that TI cells proliferate and exhibit phenotypic plasticity in vitro raise the possibility that TI cells may have similar properties in vivo.",,"['Gonzalez, Robert F.', 'Allen, Lennell', 'Dobbs, Leland G.']",,,,
,PMC,"Structure-Based Design, Synthesis, and Biological Evaluation of a Series of Novel and Reversible Inhibitors for the Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Protease",http://dx.doi.org/10.1021/jm900611t,PMC3148848,,,"We describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure-activity relationship studies, and optimized the lead structure to potent inhibitors that have shown antiviral activity against SARS-CoV infected Vero E6 cells. Based upon the X-ray crystal structure of one of the potent inhibitors 24-bound to SARS-CoV PLpro, a drug-design template was created. Our structure-based modification led to the design of a more potent inhibitor, 2 (enzyme IC(50) = 0.46 μM; antiviral EC(50) = 12.5 μM). Interestingly, its methylamine derivative 49 displayed good enzyme inhibitory potency (IC(50) = 1.3 μM) and most potent SARS antiviral activity (EC(50) = 2.5 μM) in the series. We have carried out computational docking studies and generated a predictive 3D-QSAR model for SARS-CoV PLpro inhibitors.",,"['Ghosh, Arun K.', 'Takayama, Jun', 'Aubin, Yoann', 'Ratia, Kiira', 'Chaudhuri, Rima', 'Baez, Yahira', 'Sleeman, Katrina', 'Coughlin, Melissa', 'Nichols, Daniel B.', 'Mulhearn, Debbie C.', 'Prabhakar, Bellur S.', 'Baker, Susan C.', 'Johnson, Michael E.', 'Mesecar, Andrew D.']",,,,
,PMC,Rhesus Theta-Defensin Prevents Death in a Mouse Model of Severe Acute Respiratory Syndrome Coronavirus Pulmonary Disease,http://dx.doi.org/10.1128/JVI.01363-09,PMC2772759,,,"We evaluated the efficacy of rhesus theta-defensin 1 (RTD-1), a novel cyclic antimicrobial peptide, as a prophylactic antiviral in a mouse model of severe acute respiratory syndrome (SARS) coronavirus (CoV) lung disease. BALB/c mice exposed to a mouse-adapted strain of SARS-CoV demonstrated 100% survival and modest reductions in lung pathology without reductions in virus titer when treated with two intranasal doses of RTD-1, while mortality in untreated mice was ∼75%. RTD-1-treated, SARS-CoV-infected mice displayed altered lung tissue cytokine responses 2 and 4 days postinfection compared to those of untreated animals, suggesting that one possible mechanism of action for RTD-1 is immunomodulatory.",,"['Wohlford-Lenane, Christine L.', 'Meyerholz, David K.', 'Perlman, Stanley', 'Zhou, Haixia', 'Tran, Dat', 'Selsted, Michael E.', 'McCray, Paul B.']",,,,
,PMC,Genetic Heterogeneity and Recombination in Canine Noroviruses,http://dx.doi.org/10.1128/JVI.01385-09,PMC2772758,,,"Alphatronlike (genogroup IV [GIV]) noroviruses (NoVs) have been recently identified in carnivores. By screening a collection of 183 fecal samples collected during 2007 from dogs with enteric signs, the overall NoV prevalence was found to be 2.2% (4/183). A unique strain, Bari/91/07/ITA, resembled GIV.2 NoVs in its ORF1 (polymerase complex), while it was genetically unrelated in its full-length ORF2 (capsid gene) to GIV animal and human NoVs (54.0 to 54.4% amino acid identity) and to any other NoV genogroup (<54.7% amino acid identity). It displayed the highest identity (58.1% amino acid identity) to unclassified human strain Chiba/040502/04/Jp. Interestingly, the very 5′ end of ORF2 of the canine virus matched short noroviral sequences (88.9% nucleotide identity and 98.9% amino acid identity) identified from oysters in Japan, indicating that similar viruses may be common environmental contaminants.",,"['Martella, Vito', 'Decaro, Nicola', 'Lorusso, Eleonora', 'Radogna, Arianna', 'Moschidou, Paschalina', 'Amorisco, Francesca', 'Lucente, Maria Stella', 'Desario, Costantina', 'Mari, Viviana', 'Elia, Gabriella', 'Banyai, Krisztian', 'Carmichael, Leland Eugene', 'Buonavoglia, Canio']",,,,
,PMC,Suppression of a pro-apoptotic K(+) channel as a mechanism for hepatitis C virus persistence,http://dx.doi.org/10.1073/pnas.0906798106,PMC2747216,,,"An estimated 3% of the global population are infected with hepatitis C virus (HCV), and the majority of these individuals will develop chronic liver disease. As with other chronic viruses, establishment of persistent infection requires that HCV-infected cells must be refractory to a range of pro-apoptotic stimuli. In response to oxidative stress, amplification of an outward K(+) current mediated by the Kv2.1 channel, precedes the onset of apoptosis. We show here that in human hepatoma cells either infected with HCV or harboring an HCV subgenomic replicon, oxidative stress failed to initiate apoptosis via Kv2.1. The HCV NS5A protein mediated this effect by inhibiting oxidative stress-induced p38 MAPK phosphorylation of Kv2.1. The inhibition of a host cell K(+) channel by a viral protein is a hitherto undescribed viral anti-apoptotic mechanism and represents a potential target for antiviral therapy.",,"['Mankouri, Jamel', 'Dallas, Mark L.', 'Hughes, Mair E.', 'Griffin, Stephen D. C.', 'Macdonald, Andrew', 'Peers, Chris', 'Harris, Mark']",,,,
,PMC,Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys,http://dx.doi.org/10.1136/bmj.b3391,PMC2731837,19706937,CC BY-NC,"Objective To assess the acceptability of pre-pandemic influenza vaccination among healthcare workers in public hospitals in Hong Kong and the effect of escalation in the World Health Organization’s alert level for an influenza pandemic. Design Repeated cross sectional studies using self administered, anonymous questionnaires Setting Surveys at 31 hospital departments of internal medicine, paediatrics, and emergency medicine under the Hong Kong Hospital Authority from January to March 2009 and in May 2009 Participants 2255 healthcare workers completed the questionnaires in the two studies. They were doctors, nurses, or allied health professionals working in the public hospital system. Main outcome measures Stated willingness to accept pre-pandemic influenza vaccination (influenza A subtypes H5N1 or H1N1) and its associating factors. Results The overall willingness to accept pre-pandemic H5N1 vaccine was only 28.4% in the first survey, conducted at WHO influenza pandemic alert phase 3. No significant changes in the level of willingness to accept pre-pandemic H5N1 vaccine were observed despite the escalation to alert phase 5. The willingness to accept pre-pandemic H1N1 vaccine was 47.9% among healthcare workers when the WHO alert level was at phase 5. The most common reasons for an intention to accept were “wish to be protected” and “following health authority’s advice.” The major barriers identified were fear of side effects and doubts about efficacy. More than half of the respondents thought nurses should be the first priority group to receive the vaccines. The strongest positive associating factors were history of seasonal influenza vaccination and perceived risk of contracting the infection. Conclusions The willingness to accept pre-pandemic influenza vaccination was low, and no significant effect was observed with the change in WHO alert level. Further studies are required to elucidate the root cause of the low intention to accept pre-pandemic vaccination.",2009 Aug 25,"['Chor, Josette S Y', 'Ngai, Karry LK', 'Goggins, William B', 'Wong, Martin C S', 'Wong, Samuel Y S', 'Lee, Nelson', 'Leung, Ting-fan', 'Rainer, Timothy H', 'Griffiths, Sian', 'Chan, Paul K S']",BMJ,,,
,PMC,Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors,http://dx.doi.org/10.1038/nbt.1560,PMC2791695,,,"Prostate cancer cells expressing prostate-specific membrane antigen (PSMA) have been targeted with RNA aptamer–small interfering (si)RNA chimeras, but therapeutic efficacy in vivo was demonstrated only with intratumoral injection. Clinical translation of this approach will require chimeras that are effective when administered systemically and are amenable to chemical synthesis. To these ends, we enhanced the silencing activity and specificity of aptamer-siRNA chimeras by incorporating modifications that enable more efficient processing of the siRNA by the cellular machinery. These included adding 2-nucleotide 3´-overhangs and optimizing the thermodynamic profile and structure of the duplex to favor processing of the siRNA guide strand. We also truncated the aptamer portion of the chimeras to facilitate large-scale chemical synthesis. The optimized chimeras resulted in pronounced regression of PSMA-expressing tumors in athymic mice after systemic administration. Anti-tumor activity was further enhanced by appending a polyethylene glycol moiety, which increased the chimeras’ circulating half-life.",,"['Dassie, Justin P', 'Liu, Xiu-ying', 'Thomas, Gregory S', 'Whitaker, Ryan M', 'Thiel, Kristina W', 'Stockdale, Katie R', 'Meyerholz, David K', 'McCaffrey, Anton P', 'McNamara, James O', 'Giangrande, Paloma H']",,,,
,PMC,Abnormal regulation of TSG101 in mice with spongiform neurodegeneration,http://dx.doi.org/10.1016/j.bbadis.2009.08.009,PMC2755232,,,"Spongiform neurodegeneration is characterized by the appearance of vacuoles throughout the central nervous system. It has many potential causes, but the underlying cellular mechanisms are not well understood. Mice lacking the E3 ubiquitin ligase Mahogunin Ring Finger-1 (MGRN1) develop age-dependent spongiform encephalopathy. We identified an interaction between a “PSAP” motif in MGRN1 and the ubiquitin E2 variant (UEV) domain of TSG101, a component of the endosomal sorting complex required for transport I (ESCRT-I), and demonstrate that MGRN1 multimonoubiquitinates TSG101. We examined the in vivo consequences of loss of MGRN1 on TSG101 expression and function in the mouse brain. The pattern of TSG101 ubiquitination differed in the brains of wild-type mice and Mgrn1 null mutant mice: at 1 month of age, null mutant mice had less ubiquitinated TSG101, while in adults, mutant mice had more ubiquitinated, insoluble TSG101 than wild-type mice. There was an associated increase in epidermal growth factor receptor (EGFR) levels in mutant brains. These results suggest that loss of MGRN1 promotes ubiquitination of TSG101 by other E3s and may prevent its disassociation from endosomal membranes or cause it to form insoluble aggregates. Our data implicate loss of normal TSG101 function in endo-lysosomal trafficking in the pathogenesis of spongiform neurodegeneration in Mgrn1 null mutant mice.",,"['Jiao, Jian', 'Sun, Kaihua', 'Walker, Will P.', 'Bagher, Pooneh', 'Cota, Christina D.', 'Gunn, Teresa M.']",,,,
,PMC,Gene Expression Profiles of HIV-1-Infected Glia and Brain: Toward Better Understanding of the Role of Astrocytes in HIV-1-Associated Neurocognitive Disorders,http://dx.doi.org/10.1007/s11481-009-9167-1,PMC3107560,,,"Astrocytes are the major cellular component of the central nervous system (CNS), and they play multiple roles in brain development, normal brain function, and CNS responses to pathogens and injury. The functional versatility of astrocytes is linked to their ability to respond to a wide array of biological stimuli through finely orchestrated changes in cellular gene expression. Dysregulation of gene expression programs, generally by chronic exposure to pathogenic stimuli, may lead to dysfunction of astrocytes and contribute to neuropathogenesis. Here, we review studies that employ functional genomics to characterize the effects of HIV-1 and viral pathogenic proteins on cellular gene expression in astrocytes in vitro. We also present the first microarray analysis of primary mouse astrocytes exposed to HIV-1 in culture. In spite of different experimental conditions and microarray platforms used, comparison of the astrocyte array data sets reveals several common gene-regulatory changes that may underlie responses of these cells to HIV-1 and its proteins. We also compared the transcriptional profiles of astrocytes with those obtained in analyses of brain tissues of patients with HIV-1 dementia and macaques infected with simian immunodeficiency virus (SIV). Notably, many of the gene characteristics of responses to HIV-1 in cultured astrocytes were also altered in HIV-1 or SIV-infected brains. Functional genomics, in conjunction with other approaches, may help clarify the role of astrocytes in HIV-1 neuropathogenesis.",,"['Borjabad, Alejandra', 'Brooks, Andrew I.', 'Volsky, David J.']",,,,
,PMC,Cytokine determinants of viral tropism,http://dx.doi.org/10.1038/nri2623,PMC4373421,,,"The specificity of a given virus for a ceil type, tissue or species — collectively known as viral tropism — is an important factor in determining the outcome of viral infection in any particular host. Owing to the increased prevalence of zoonotic infections and the threat of emerging and re-emerging pathogens, gaining a better understanding of the factors that determine viral tropism has become particularly important. In this Review, we summarize our current understanding of the central role of antiviral and pro-inflammatory cytokines, particularly the interferons and tumour necrosis factor, in dictating viral tropism and how these cytokine pathways can be exploited therapeutically for cancer treatment and to better counter future threats from emerging zoonotic pathogens.",,"['McFadden, Grant', 'Mohamed, Mohamed R.', 'Rahman, Masmudur M.', 'Bartee, Eric']",,,,
,PMC,,,PMC2762335,20020673,CC BY,,2009 Aug 21,,PLoS Curr,,,
,PMC,The Era of Genomic Epidemiology,http://dx.doi.org/10.1159/000235639,PMC2826447,,,"The recent revolution in genomics is already having a profound impact on the practice of epidemiology. The purpose of this commentary is to demonstrate how genomics and epidemiology will continue to rely heavily on each other, now and in the future, by illustrating a number of interaction points between these 2 disciplines: (1) the use of genomics to estimate disease heritability; (2) the impact of genomics on analytical study design; (3) how genome-wide data can be employed to effectively overcome residual population stratification arising from selection bias; (4) the importance of genomics as a tool in epidemiological investigation; (5) the importance of epidemiology in the collection of adequately phenotyped samples for genomics studies, and (6) for unraveling the clinical and therapeutic relevance of genetic variants once they are discovered.",,"Traynor, Bryan J.",,,,
,PMC,Developmental delays consistent with cochlear hypothyroidism contribute to failure to develop hearing in mice lacking Slc26a4/pendrin expression,http://dx.doi.org/10.1152/ajprenal.00011.2009,PMC2781347,,,"Mutations of SLC26A4 cause an enlarged vestibular aqueduct, nonsyndromic deafness, and deafness as part of Pendred syndrome. SLC26A4 encodes pendrin, an anion exchanger located in the cochlea, thyroid, and kidney. The goal of the present study was to determine whether developmental delays, possibly mediated by systemic or local hypothyroidism, contribute to the failure to develop hearing in mice lacking Slc26a4 (Slc26a4(−/−)). We evaluated thyroid function by voltage and pH measurements, by array-assisted gene expression analysis, and by determination of plasma thyroxine levels. Cochlear development was evaluated for signs of hypothyroidism by microscopy, in situ hybridization, and quantitative RT-PCR. No differences in plasma thyroxine levels were found in Slc26a4(−/−) and sex-matched Slc26a4(+/−) littermates between postnatal day 5 (P5) and P90. In adult Slc26a4(−/−) mice, the transepithelial potential and the pH of thyroid follicles were reduced. No differences in the expression of genes that participate in thyroid hormone synthesis or ion transport were observed at P15, when plasma thyroxine levels peaked. Scala media of the cochlea was 10-fold enlarged, bulging into and thereby displacing fibrocytes, which express Dio2 to generate a cochlear thyroid hormone peak at P7. Cochlear development, including tunnel opening, arrival of efferent innervation at outer hair cells, endochondral and intramembraneous ossification, and developmental changes in the expression of Dio2, Dio3, and Tectb were delayed by 1–4 days. These data suggest that pendrin functions as a HCO(3)(−) transporter in the thyroid, that Slc26a4(−/−) mice are systemically euthyroid, and that delays in cochlear development, possibly due to local hypothyroidism, lead to the failure to develop hearing.",,"['Wangemann, Philine', 'Kim, Hyoung-Mi', 'Billings, Sara', 'Nakaya, Kazuhiro', 'Li, Xiangming', 'Singh, Ruchira', 'Sharlin, David S.', 'Forrest, Douglas', 'Marcus, Daniel C.', 'Fong, Peying']",,,,
,PMC,Mechanisms of Primary Axonal Damage in a Viral Model of Multiple Sclerosis,http://dx.doi.org/10.1523/JNEUROSCI.1975-09.2009,PMC2747667,,,"Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Recent studies have demonstrated that significant axonal injury also occurs in MS patients and correlates with neurological dysfunction, but it is not known whether this neuronal damage is a primary disease process, or occurs only secondary to demyelination. In the current studies, neurotropic strains of mouse hepatitis virus (MHV) that induce meningitis, encephalitis, and demyelination in the CNS, an animal model of MS, were used to evaluate mechanisms of axonal injury. The pathogenic properties of genetically engineered isogenic spike protein recombinant demyelinating and nondemyelinating strains of MHV were compared. Studies demonstrate that a demyelinating strain of MHV causes concomitant axonal loss and macrophage-mediated demyelination. The mechanism of axonal loss and demyelination in MHV infection is dependent on successful transport of virus from gray matter to white matter using the MHV host attachment spike glycoprotein. Our data show that axonal loss and demyelination can be independent direct viral cytopathic events, and suggest that similar direct axonal damage may occur in MS. These results have important implications for the design of neuroprotective strategies for CNS demyelinating disease, and our model identifies the spike protein as a therapeutic target to prevent axonal transport of neurotropic viruses.",,"['Das Sarma, Jayasri', 'Kenyon, Lawrence C.', 'Hingley, Susan T.', 'Shindler, Kenneth S.']",,,,
,PMC,The Pre-Transmembrane Domain of the Autographa californica Multicapsid Nucleopolyhedrovirus GP64 Protein Is Critical for Membrane Fusion and Virus Infectivity,http://dx.doi.org/10.1128/JVI.01085-09,PMC2772811,,,"The envelope glycoprotein, GP64, of the baculovirus Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) is a class III viral fusion protein that mediates pH-triggered membrane fusion during virus entry. Viral fusion glycoproteins from many viruses contain a short region in the ectodomain and near the transmembrane domain, referred to as the pre-transmembrane (PTM) domain. In some cases, the PTM domain is rich in aromatic amino acids and plays an important role in membrane fusion. Although the 23-amino-acid (aa) PTM domain of AcMNPV GP64 lacks aromatic amino acids, we asked whether this region might also play a significant role in membrane fusion. We generated alanine scanning and single and multiple amino acid substitutions in the GP64 PTM domain. We specifically focused on amino acid positions conserved between baculovirus GP64 and thogotovirus GP75 proteins, as well as hydrophobic and charged amino acids. For each PTM-modified construct, we examined trimerization, cell surface localization, and membrane fusion activity. Membrane merger and pore formation were also examined. We identified eight aa positions that are important for membrane fusion activity. Critical positions were not clustered in the linear sequence but were distributed throughout the PTM domain. While charged residues were not critical or essential, three hydrophobic amino acids (L465, L476, and L480) played an important role in membrane fusion activity and appear to be involved in formation of the fusion pore. We also asked whether selected GP64 constructs were capable of rescuing a gp64null AcMNPV virus. These studies suggested that several conserved residues (T463, G460, G462, and G474) were not required for membrane fusion but were important for budding and viral infectivity.",,"['Li, Zhaofei', 'Blissard, Gary W.']",,,,
,PMC,Elucidation of the stability and functional regions of the human coronavirus OC43 nucleocapsid protein,http://dx.doi.org/10.1002/pro.225,PMC2788276,,,"Human coronavirus OC43 (HCoV-OC43) is one of the causes of the “common cold” in human during seasons of cold weather. The primary function of the HCoV-OC43 nucleocapsid protein (N protein) is to recognize viral genomic RNA, which leads to ribonucleocapsid formation. Here, we characterized the stability and identified the functional regions of the recombinant HCoV-OC43 N protein. Circular dichroism and fluorescence measurements revealed that the HCoV-OC43 N protein is more highly ordered and stabler than the SARS-CoV N protein previously studied. Surface plasmon resonance (SPR) experiments showed that the affinity of HCoV-OC43 N protein for RNA was approximately fivefold higher than that of N protein for DNA. Moreover, we found that the HCoV-OC43 N protein contains three RNA-binding regions in its N-terminal region (residues 1–173) and central-linker region (residues 174–232 and 233–300). The binding affinities of the truncated N proteins and RNA follow the order: residues 1–173–residues 233–300 > residues 174–232. SPR experiments demonstrated that the C-terminal region (residues 301–448) of HCoV-OC43 N protein lacks RNA-binding activity, while crosslinking and gel filtration analyses revealed that the C-terminal region is mainly involved in the oligomerization of the HCoV-OC43 N protein. This study may benefit the understanding of the mechanism of HCoV-OC43 nucleocapsid formation.",,"['Huang, Chun-Yu', 'Hsu, Yen-Lan', 'Chiang, Wan-Ling', 'Hou, Ming-Hon']",,,,
,PMC,Characterization of Chikungunya pseudotyped viruses: Identification of refractory cell lines and demonstration of cellular tropism differences mediated by mutations in E1 glycoprotein,http://dx.doi.org/10.1016/j.virol.2009.07.013,PMC2760448,,,"Chikungunya virus (CHIKV) is an alphavirus responsible for a number of large outbreaks. Here we describe the efficient incorporation of CHIKV envelope glycoproteins into lentiviral and rhabdoviral particles. Vectors pseudotyped with CHIKV envelope proteins efficiently transduced many cell types from different species. However, hematopoietic cell types were either partially or completely refractory. A mutation in E1 (A226V) has been linked with expansion of tropism for mosquito species, although differences in in vitro infection of mosquito cell lines have not been noted. However, pseudovirion infectivity assays detected subtle differences in infection of mosquito cells, suggesting an explanation for the changes in mosquito tropism. The presence of C-type lectins increased CHIKV pseudotyped vector infectivity, but not infection of refractory cells, suggesting that they act as attachment factors rather than primary receptors. CHIKV pseudotypes will serve as an important tool for the study of neutralizing antibodies and the analysis of envelope glycoprotein functions.",,"['Salvador, Beatriz', 'Zhou, Yanchen', 'Michault, Alain', 'Muench, Marcus O.', 'Simmons, Graham']",,,,
,PMC,"Recombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity",http://dx.doi.org/10.1016/j.virol.2009.07.018,PMC2753736,,,"Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease. The potential recurrence of the disease from animal reservoirs highlights the significance of development of safe and efficient vaccines to prevent a future SARS epidemic. In this study, we expressed the recombinant receptor-binding domain (rRBD) in mammalian (293T) cells, insect (Sf9) cells, and E. coli, respectively, and compared their immunogenicity and protection against SARS-CoV infection in an established mouse model. Our results show that all rRBD proteins expressed in the above systems maintained intact conformation, being able to induce highly potent neutralizing antibody responses and complete protective immunity against SARS-CoV challenge in mice, albeit the rRBD expressed in 293T cells elicited stronger humoral immune responses with significantly higher neutralizing activity (P < 0.05) than those expressed in Sf9 and E. coli cells. These results suggest that all three rRBDs are effective in eliciting immune responses and protection against SARS-CoV and any of the above expression systems can be used for production of rRBD-based SARS subunit vaccines. Preference will be given to rRBD expressed in mammalian cells for future evaluation of the vaccine efficacy in a non-human primate model of SARS because of its ability to refold into a native conformation more readily and to induce higher level of neutralizing antibody responses than those expressed in E. coli and insect cells.",,"['Du, Lanying', 'Zhao, Guangyu', 'Chan, Chris CS', 'Sun, Shihui', 'Chen, Min', 'Liu, Zhonghua', 'Guo, Hongxiang', 'He, Yuxian', 'Zhou, Yusen', 'Zheng, Bo-Jian', 'Jiang, Shibo']",,,,
,PMC,Plant-derived triterpenoids and analogues as antitumor and anti-HIV agents,http://dx.doi.org/10.1039/b810774m,PMC3773821,,,"This article reviews the antitumor and anti-HIV activities of naturally occurring triterpenoids, including the lupane, ursane, oleanane, lanostane, dammarane, and miscellaneous scaffolds. Structure–activity relationships of selected natural compounds and their synthetic derivatives are also discussed.",,"['Kuo, Reen-Yen', 'Qian, Keduo', 'Morris-Natschke, Susan L.', 'Lee, Kuo-Hsiung']",,,,
,PMC,Two-Step Conformational Changes in a Coronavirus Envelope Glycoprotein Mediated by Receptor Binding and Proteolysis,http://dx.doi.org/10.1128/JVI.00959-09,PMC2772765,,,"The coronaviruses mouse hepatitis virus type 2 (MHV-2) and severe acute respiratory syndrome coronavirus (SARS-CoV) utilize proteases to enter host cells. Upon receptor binding, the spike (S) proteins of both viruses are activated for membrane fusion by proteases, such as trypsin, present in the environment, facilitating virus entry from the cell surface. In contrast, in the absence of extracellular proteases, these viruses can enter cells via an endosomal pathway and utilize endosomal cathepsins for S protein activation. We demonstrate that the MHV-2 S protein uses multistep conformational changes for membrane fusion. After interaction with a soluble form of the MHV receptor (CEACAM1a), the metastable form of S protein is converted to a stable trimer, as revealed by mildly denaturing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Liposome-binding assays indicate that the receptor-bound virions are associated with the target membrane through hydrophobic interactions. The exposure of receptor-bound S protein to trypsin or cathepsin L (CPL) induces the formation of six-helix bundles (6HB), the final conformation. This trypsin- or CPL-mediated conversion to 6HB can be blocked by a heptad repeat peptide known to block the formation of 6HB. Although trypsin treatment enabled receptor-bound MHV-2 to enter from the cell surface, CPL failed to do so. Interestingly, consecutive treatment with CPL and then chlorpromazine enabled a portion of the virus to enter from cell surface. These results suggest that trypsin suffices for the induction of membrane fusion of receptor-primed S protein, but an additional unidentified cellular factor is required to trigger membrane fusion by CPL.",,"['Matsuyama, Shutoku', 'Taguchi, Fumihiro']",,,,
,PMC,A Gammaherpesvirus Ubiquitin-Specific Protease Is Involved in the Establishment of Murine Gammaherpesvirus 68 Infection,http://dx.doi.org/10.1128/JVI.01017-09,PMC2753118,,,"Murine gammaherpesvirus 68 (MHV-68) contains a ubiquitin (Ub)-specific cysteine protease (USP) domain embedded within the large tegument protein ORF64, as do all other herpesviruses. The biological role of this protease is still unclear, but for the alphaherpesvirus Marek's disease virus, its USP is involved in T-cell lymphoma formation. We here study the role of the MHV-68 USP, encoded by ORF64. By constructing a mutant virus with a single cysteine-to-alanine replacement in the active site of ORF64, we demonstrate that the USP activity of ORF64 is abolished. The mutant virus replicates less efficiently in vitro, and plaque size is reduced compared to that of a revertant virus. Electron microscopy of infected cells did not reveal any obvious differences in virion morphogenesis or differences in egress for the mutant and revertant viruses. Intraperitoneal infection of C57/BL6 mice demonstrates that the mutant virus is generally cleared by day 7, indicating a role for the USP in the persistence of MHV-68 infection or efficient replication. However, the USP activity in MHV-68 is unlikely to be involved in the establishment of latency or reactivation, since we observed no significant difference in viral DNA genome copy number in the spleen or in the number of cells that reactivate MHV-68 from latency. Our results for MHV-68 ORF64 are consistent with an enzymatic function of the tegument protein that is beneficial to the virus during acute infection, particularly in vivo.",,"['Gredmark-Russ, Sara', 'Isaacson, Marisa K.', 'Kattenhorn, Lisa', 'Cheung, Evelyn J.', 'Watson, Nicki', 'Ploegh, Hidde L.']",,,,
,PMC,Glucose-regulated Protein 78 Is an Intracellular Antiviral Factor against Hepatitis B Virus,http://dx.doi.org/10.1074/mcp.M900180-MCP200,PMC2773723,,,"Hepatitis B virus (HBV) infection is a global public health problem that plays a crucial role in the pathogenesis of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. However, the pathogenesis of HBV infection and the mechanisms of host-virus interactions are still elusive. In this study, two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomics were applied to analyze the host response to HBV using an inducible HBV-producing cell line, HepAD38. Twenty-three proteins were identified as differentially expressed with glucose-regulated protein 78 (GRP78) as one of the most significantly up-regulated proteins induced by HBV replication. This induction was further confirmed in both HepAD38 and HepG2 cells transfected with HBV-producing plasmids by real time RT-PCR and Western blotting as well as in HBV-infected human liver biopsies by immunohistochemistry. Knockdown of GRP78 expression by RNA interference resulted in a significant increase of both intracellular and extracellular HBV virions in the transient HBV-producing HepG2 cells concomitant with enhanced levels of hepatitis B surface antigen and e antigen in the culture medium. Conversely overexpression of GRP78 in HepG2 cells led to HBV suppression concomitant with induction of the positive regulatory circuit of GRP78 and interferon-β1 (IFN-β1). In this connection, the IFN-β1-mediated 2′,5′-oligoadenylate synthetase and RNase L signaling pathway was noted to be activated in GRP78-overexpressing HepG2 cells. Moreover GRP78 was significantly down-regulated in the livers of chronic hepatitis B patients after effective anti-HBV treatment (p = 0.019) as compared with their counterpart pretreatment liver biopsies. In conclusion, the present study demonstrates for the first time that GRP78 functions as an endogenous anti-HBV factor via the IFN-β1-2′,5′-oligoadenylate synthetase-RNase L pathway in hepatocytes. Induction of hepatic GRP78 may provide a novel therapeutic approach in treating HBV infection.",,"['Ma, Yan', 'Yu, Jun', 'Chan, Henry L. Y.', 'Chen, Yang-chao', 'Wang, Hua', 'Chen, Ying', 'Chan, Chu-yan', 'Go, Minnie Y. Y.', 'Tsai, Sau-na', 'Ngai, Sai-ming', 'To, Ka-fai', 'Tong, Joanna H. M.', 'He, Qing-Yu', 'Sung, Joseph J. Y.', 'Kung, Hsiang-fu', 'Cheng, Christopher H. K.', 'He, Ming-liang']",,,,
,PMC,"Chromosome 14 transfer and functional studies identify a candidate tumor suppressor gene, Mirror image polydactyly 1, in nasopharyngeal carcinoma",http://dx.doi.org/10.1073/pnas.0900198106,PMC2732794,,,"Chromosome 14 allelic loss is common in nasopharyngeal carcinoma (NPC) and may reflect essential tumor suppressor gene loss in tumorigenesis. An intact chromosome 14 was transferred to an NPC cell line using a microcell-mediated chromosome transfer approach. Microcell hybrids (MCHs) containing intact exogenously transferred chromosome 14 were tumor suppressive in athymic mice, demonstrating that intact chromosome 14 NPC MCHs are able to suppress tumor growth in mice. Comparative analysis of these MCHs and their derived tumor segregants identified 4 commonly eliminated tumor-suppressive CRs. Here we provide functional evidence that a gene, Mirror-Image POLydactyly 1 (MIPOL1), which maps within a single 14q13.1–13.3 CR and that hitherto has been reported to be associated only with a developmental disorder, specifically suppresses in vivo tumor formation. MIPOL1 gene expression is down-regulated in all NPC cell lines and in ≈63% of NPC tumors via promoter hypermethylation and allelic loss. SLC25A21 and FOXA1, 2 neighboring genes mapping to this region, did not show this frequent down-regulated gene expression or promoter hypermethylation, precluding possible global methylation effects and providing further evidence that MIPOL1 plays a unique role in NPC. The protein localizes mainly to the nucleus. Re-expression of MIPOL1 in the stable transfectants induces cell cycle arrest. MIPOL1 tumor suppression is related to up-regulation of the p21(WAF1/CIP1) and p27(KIP1) protein pathways. This study provides compelling evidence that chromosome 14 harbors tumor suppressor genes associated with NPC and that a candidate gene, MIPOL1, is associated with tumor development.",,"['Cheung, Arthur Kwok Leung', 'Lung, Hong Lok', 'Ko, Josephine Mun Yee', 'Cheng, Yue', 'Stanbridge, Eric J.', 'Zabarovsky, Eugene R.', 'Nicholls, John M.', 'Chua, Daniel', 'Tsao, Sai Wah', 'Guan, Xin-Yuan', 'Lung, Maria Li']",,,,
,PMC,Activation of Tumor Suppressor Protein p53 Is Required for Theiler's Murine Encephalomyelitis Virus-Induced Apoptosis in M1-D Macrophages,http://dx.doi.org/10.1128/JVI.01030-09,PMC2753135,,,"Theiler's murine encephalomyelitis virus (TMEV) is a highly cytolytic picornavirus that persists in the mouse central nervous system (CNS) largely in macrophages with infection maintained by macrophage-to-macrophage spread. Infected macrophages in the CNS undergo apoptosis. We recently showed that M1-D macrophages infected with the low-neurovirulence TMEV BeAn virus became apoptotic through the mitochondrial pathway that is Bax mediated. Our present analyses of the molecular events and signaling pathway(s) culminating in the mitochondrial outer membrane permeabilization that initiates the caspase cascade and apoptosis of BeAn virus-infected M1-D macrophages revealed activation of p38 mitogen-activated protein kinase by 2 to 3 h postinfection (p.i.), followed by phosphorylation of tumor suppressor protein p53 Ser 15 at 3 to 6 h p.i., stabilizing p53 levels until 6 h p.i. Activated p53 upregulated the transcription of proapoptotic puma and noxa genes at 2 to 4 h p.i. and their BH3-only protein expression, followed by the loss of detectable prosurvival Mcl-1 and A1 proteins at 4 to 10 h p.i. Degradation of the prosurvival proteins is known to release Bax, which forms homo-oligomers and translocates into and permeabilizes the mitochondrial outer membrane. Inhibition of phospho-p38 by two specific inhibitors, SB203580 and BIRB796, led to a significant decrease in apoptosis at 10 h p.i., with no effect on virus titers (only SB203580 tested). Together, these data indicate that p53 activation is required for the induction of apoptosis in infected M1-D cells.",,"['Son, Kyung-No', 'Pugazhenthi, Subbiah', 'Lipton, Howard L.']",,,,
,PMC,"Turnip Mosaic Virus RNA Replication Complex Vesicles Are Mobile, Align with Microfilaments, and Are Each Derived from a Single Viral Genome",http://dx.doi.org/10.1128/JVI.00819-09,PMC2753101,,,"Nicotiana benthamiana plants were agroinoculated with an infectious cDNA clone of Turnip mosaic virus (TuMV) that was engineered to express a fluorescent protein (green fluorescent protein [GFP] or mCherry) fused to the viral 6K(2) protein known to induce vesicle formation. Cytoplasmic fluorescent discrete protein structures were observed in infected cells, corresponding to the vesicles containing the viral RNA replication complex. The vesicles were motile and aligned with microfilaments. Intracellular movement of the vesicles was inhibited when cells were infiltrated with latrunculin B, an inhibitor of microfilament polymerization. It was also observed that viral accumulation in the presence of this drug was reduced. These data indicate that microfilaments are used for vesicle movement and are necessary for virus production. Biogenesis of the vesicles was further investigated by infecting cells with two recombinant TuMV strains: one expressed 6K(2)GFP and the other expressed 6K(2)mCherry. Green- and red-only vesicles were observed within the same cell, suggesting that each vesicle originated from a single viral genome. There were also vesicles that exhibited sectors of green, red, or yellow fluorescence, an indication that fusion among individual vesicles is possible. Protoplasts derived from TuMV-infected N. benthamiana leaves were isolated. Using immunofluorescence staining and confocal microscopy, viral RNA synthesis sites were visualized as punctate structures distributed throughout the cytoplasm. The viral proteins VPg-Pro, RNA-dependent RNA polymerase, and cytoplasmic inclusion protein (helicase) and host translation factors were found to be associated with these structures. A single-genome origin and presence of protein synthetic machinery components suggest that translation of viral RNA is taking place within the vesicle.",,"['Cotton, Sophie', 'Grangeon, Romain', 'Thivierge, Karine', 'Mathieu, Isabelle', 'Ide, Christine', 'Wei, Taiyun', 'Wang, Aiming', 'Laliberté, Jean-François']",,,,
,PMC,Infectious disease experts expect the unexpected with respect to swine flu,http://dx.doi.org/10.1503/cmaj.091176,PMC2717657,,,,,"Webster, Paul",,,,
,PMC,The autophagy machinery is required to initiate hepatitis C virus replication,http://dx.doi.org/10.1073/pnas.0907344106,PMC2729017,,,"In addition to its cellular homeostasis function, autophagy is emerging as a central component of antimicrobial host defense against diverse infections. To counteract this mechanism, many pathogens have evolved to evade, subvert, or exploit autophagy. Here, we report that autophagy proteins (i.e., Beclin-1, Atg4B, Atg5, and Atg12) are proviral factors required for translation of incoming hepatitis C virus (HCV) RNA and, thereby, for initiation of HCV replication, but they are not required once infection is established. These results illustrate a previously unappreciated role for autophagy in the establishment of a viral infection and they suggest that different host factors regulate the translation of incoming viral genome and translation of progeny HCV RNA once replication is established.",,"['Dreux, Marlène', 'Gastaminza, Pablo', 'Wieland, Stefan F.', 'Chisari, Francis V.']",,,,
,PMC,Nosocomial Contamination of Laryngoscope Handles: Challenging Current Guidelines,http://dx.doi.org/10.1213/ane.0b013e3181ac1080,PMC4006105,,,"BACKGROUND: Laryngoscope blades are often cleaned between cases according to well-defined protocols. However, despite evidence that laryngoscope handles could be a source of nosocomial infection, neither our institution nor the American Society of Anesthesiologists has any specific guidelines for handle disinfection. We hypothesized that laryngoscope handles may be sufficiently contaminated with bacteria and viruses to justify the implementation of new handle-cleaning protocols. METHODS: Sixty laryngoscope handles from the adult operating rooms were sampled with premoistened sterile swabs. Collection was performed between cases, in operating rooms hosting a broad variety of subspecialty procedures, after the room and equipment had been thoroughly cleaned for the subsequent case. Samples from 40 handles were sent for aerobic bacterial culture, and antimicrobial susceptibility testing was performed for significant isolates. Samples from 20 handles were examined for viral contamination using a polymerase chain reaction assay that detects 17 respiratory viruses. RESULTS: Of the 40 samples sent for culture, 30 (75%) were positive for bacterial contamination. Of these positive cultures, 25 (62.5%) yielded coagulase-negative staphylococci, seven (17.5%) Bacillus spp. not anthracis, three (7.5%) α-hemolytic Streptococcus spp., and one each (2.5%) of Enterococcus spp., Staphylococcus aureus (S. aureus), and Corynebacterium spp. No vancomycin-resistant enterococci, methicillin-resistant S. aureus, or Gram-negative rods were detected. All viral tests were negative. CONCLUSION: We found a high incidence of bacterial contamination of laryngoscope handles despite low-level disinfection. However, no vancomycin-resistant enterococci, methicillin-resistant S. aureus, Gram-negative rods, or respiratory viruses were detected. Our results support adoption of guidelines that include, at a minimum, mandatory low-level disinfection of laryngoscope handles after each patient use.",,"['Call, Tyler R.', 'Auerbach, Frederic J.', 'Riddell, Scott W.', 'Kiska, Deanna L.', 'Thongrod, Sumena C.', 'Tham, See Wan', 'Nussmeier, Nancy A.']",,,,
,PMC,Open access: a giant leap towards bridging health inequities,http://dx.doi.org/10.2471/BLT.09.064659,PMC2733280,,,"Access to health research publications is an essential requirement in securing the chain of communication from the researcher to the front-line health worker. As the diagram of the knowledge cycle from the Canadian Institutes of Health Research shows, health knowledge generated in the world’s laboratories is passed down the information chain through publications, through its impact and application, its subsequent “translation” into appropriate contexts for different user communities, arriving finally with health workers and the general public. This article focuses on the first link in the chain, from research author to reader, and the free online access to peer-reviewed published articles that are the building blocks for future health innovation developments.",,"['Chan, Leslie', 'Arunachalam, Subbiah', 'Kirsop, Barbara']",,,,
,PMC,Risk and outbreak communication: lessons from alternative paradigms,http://dx.doi.org/10.2471/BLT.08.058149,PMC2733277,,,"Risk communication guidelines widely used in public health are based on the psychometric paradigm of risk, which focuses on risk perception at the level of individuals. However, infectious disease outbreaks and other public health emergencies are more than public health events and occur in a highly charged political, social and economic environment. This study examines other sociological and cultural approaches from scholars such as Ulrich Beck and Mary Douglas for insights on how to communicate in such environments. It recommends developing supplemental tools for outbreak communication to deal with issues such as questions of blame and fairness in risk distribution and audiences who do not accept biomedical explanations of disease.",,"Abraham, Thomas",,,,
,PMC,A social explanation for the rise and fall of global health issues,http://dx.doi.org/10.2471/BLT.08.060749,PMC2733265,,,"This paper proposes an explanation concerning why some global health issues such as HIV/AIDS attract significant attention from international and national leaders, while other issues that also represent a high mortality and morbidity burden, such as pneumonia and malnutrition, remain neglected. The rise, persistence and decline of a global health issue may best be explained by the way in which its policy community – the network of individuals and organizations concerned with the problem – comes to understand and portray the issue and establishes institutions that can sustain this portrayal. This explanation emphasizes the power of ideas and challenges interpretations of issue ascendance and decline that place primary emphasis on material, objective factors such as mortality and morbidity levels and the existence of cost-effective interventions. This explanation has implications for our understanding of strategic public health communication. If ideas in the form of issue portrayals are central, strategic communication is far from a secondary public health activity: it is at the heart of what global health policy communities do.",,"Shiffman, Jeremy",,,,
,PMC,Transparency during public health emergencies: from rhetoric to reality,http://dx.doi.org/10.2471/BLT.08.056689,PMC2733257,,,"Effective management of public health emergencies demands open and transparent public communication. The rationale for transparency has public health, strategic and ethical dimensions. Despite this, government authorities often fail to demonstrate transparency. A key step in bridging the gap between the rhetoric and reality is to define and codify transparency to put in place practical mechanisms to encourage open public health communication for emergencies. The authors demonstrate this approach using the example of the development and implementation process of a public health emergency information policy.",,"['O’Malley, P', 'Rainford, J', 'Thompson, A']",,,,
,PMC,Clostridial abomasal disease in Connecticut dairy calves,,PMC2711473,,,"Over 2 years, 24 dairy calves died of emphysematous abomasitis and abomasal bloat. Anaerobic cultures of necrotic abomasal mucosa yielded Clostridium perfringens from 10 of 15 calves. Sarcina were observed in 17 of 22 examined histologically. A change in the antibiotic regimen for newborns and improved sanitizing of feeding utensils eliminated further losses.",,"['Van Kruiningen, Herbert J.', 'Nyaoke, Carol A.', 'Sidor, Inga F.', 'Fabis, Jaroslaw J.', 'Hinckley, Lynn S.', 'Lindell, Kevin A.']",,,,
,PMC,"‘Swine flu’, to do or not to do?",http://dx.doi.org/10.7861/clinmedicine.9-4-403,PMC4952525,,,,,"Coemgenus,",,,,
,PMC,Autophagy as an antimicrobial strategy,http://dx.doi.org/10.1586/eri.09.41,PMC3280690,,,Autophagy is a process of lysosomal degradation that was originally described as a cellular response to adapt to a lack of nutrients and to enable the elimination of damaged organelles. Autophagy is increasingly recognized as a process that is also involved in innate and adaptive immune responses against pathogens. Studies on the regulation of autophagy have uncovered components of the autophagic cascade that can be manipulated pharmacologically. Approaches to modulate autophagy may result in novel strategies for the treatment and prevention of various infections.,,"Subauste, Carlos S",,,,
,PMC,Timing and severity of community acquired respiratory virus infections after myeloablative versus non-myeloablative hematopoietic stem cell transplantation,http://dx.doi.org/10.3324/haematol.2008.003186,PMC2719033,,,"BACKGROUND: Respiratory virus infections are important causes of morbidity and mortality after hematopoietic cell transplantation. Their clinical course can be severe with progression to lower respiratory tract infection, co-infection with serious pulmonary co-pathogens, and high mortality. Non-myeloablative conditioning regimens achieve engraftment without eradication of host hematopoietic cells, which potentially allows for protection against infections commonly seen in hematopoietic cell transplantation patients treated with standard intensity conditioning regimens. DESIGN AND METHODS: We performed a retrospective cohort study to measure the incidence and severity of parainfluenza types 1–4, influenza (A and B), respiratory syncitial virus and human rhinovirus disease in myeloablative versus non-myeloablative versus autologous hematopoietic cell transplantation patients. RESULTS: The incidences of all respiratory virus infections were similar in the non-myeloablative and myeloablative cohorts but less in the autologous cohort (33/420 [7.9%], 150/1593 [9.4%], and 37/751 [4.9%], respectively, p<0.0001). However, respiratory virus lower tract infections were significantly less common during the first 100 days after transplantation in non-myeloablative patients compared to myeloablative and autologous patients (1/420 [0.2%], 34/1593 [2.1%] and 16/751 [2.1%], respectively, p=0.005. Respiratory virus lower tract infection had high co-infection and attributable mortality rates. CONCLUSIONS: Respiratory virus lower tract infection during the first 100 days after hematopoietic cell transplantation was less common in persons receiving non-myeloablative conditioning regimens compared to myeloablative conditioning, despite a similar overall rate of acquisition.",,"['Schiffer, Joshua T.', 'Kirby, Kate', 'Sandmaier, Brenda', 'Storb, Rainer', 'Corey, Lawrence', 'Boeckh, Michael']",,,,
,PMC,A novel method for oral delivery of apolipoprotein mimetic peptides synthesized from all L-amino acids,http://dx.doi.org/10.1194/jlr.M800539-JLR200,PMC2724044,,,"Administered subcutaneously, D-4F or L-4F are equally efficacious, but only D-4F is orally efficacious because of digestion of L-4F by gut proteases. Orally administering niclosamide (a chlorinated salicylanilide used as a molluscicide, antihelminthic, and lampricide) in temporal proximity to oral L-4F (but not niclosamide alone) in apoE null mice resulted in significant improvement (P < 0.001) in the HDL-inflammatory index (HII), which measures the ability of HDL to inhibit LDL-induced monocyte chemotactic activity in endothelial cell cultures. Oral administration of L-[113-122]apoJ with niclosamide also resulted in significant improvement (P < 0.001) in HII. Oral administration of niclosamide and L-4F together with pravastatin to female apoE null mice at 9.5 months of age for six months significantly reduced aortic sinus lesion area (P = 0.02), en face lesion area (P = 0.033), and macrophage lesion area (P = 0.02) compared with pretreatment, indicating lesion regression. In contrast, lesions were significantly larger in mice receiving only niclosamide and pravastatin or L-4F and pravastatin (P < 0.001). In vitro niclosamide and L-4F tightly associated rendering the peptide resistant to trypsin digestion. Niclosamide itself did not inhibit trypsin activity. The combination of niclosamide with apolipoprotein mimetic peptides appears to be a promising method for oral delivery of these peptides.",,"['Navab, Mohamad', 'Ruchala, Piotr', 'Waring, Alan J.', 'Lehrer, Robert I.', 'Hama, Susan', 'Hough, Greg', 'Palgunachari, Mayakonda N.', 'Anantharamaiah, G. M.', 'Fogelman, Alan M.']",,,,
,PMC,The Pediatric Burden of Human Coronaviruses Evaluated For 20 Years,http://dx.doi.org/10.1097/INF.0b013e31819d0d27,PMC2765860,,,,,"['Talbot, H. Keipp', 'Shepherd, Bryan E.', 'Crowe, James E.', 'Griffin, Marie R.', 'Edwards, Kathryn M.', 'Podsiad, Amy B.', 'Tollefson, Sharon J.', 'Wright, Peter F.', 'Williams, John V.']",,,,
,PMC,A homogeneous cell-based bicistronic fluorescence assay for high-throughput identification of drugs that perturb viral gene recoding and read-through of nonsense stop codons,http://dx.doi.org/10.1261/rna.1586709,PMC2714747,,,"Recoding mechanisms are programmed protein synthesis events used commonly by viruses but only very rarely in cells for cellular gene expression. For example, HIV-1 has an absolute reliance on frameshifting to produce the correct ratio of key proteins critical for infectivity. To exploit such recoding sites as therapeutic targets, a simple homogeneous assay capable of detecting small perturbations in these low-frequency (<5%) events is required. Current assays based on dual luciferase reporters use expensive substrates and are labor-intensive, both impediments for high-throughput screening. We have developed a cell-based bifluorophore assay able to measure accurately small recoding changes (<0.1%) with a high Z′-factor in 24- or 96-well formats that could be extended to 384 wells. In cases of nonsense mutations arising within coding regions of genes, the assay is suitable for assessing the potential of screened compounds to increase read-through at these nonprogrammed stop signals of variable termination efficiency.",,"['Cardno, Tony S.', 'Poole, Elizabeth S.', 'Mathew, Suneeth F.', 'Graves, Ryan', 'Tate, Warren P.']",,,,
,PMC,"Rapid Multiplex Reverse Transcription-PCR Typing of Influenza A and B Virus, and Subtyping of Influenza A Virus into H1, 2, 3, 5, 7, 9, N1 (Human), N1 (Animal), N2, and N7, Including Typing of Novel Swine Origin Influenza A (H1N1) Virus, during the 2009 Outbreak in Milwaukee, Wisconsin",http://dx.doi.org/10.1128/JCM.00998-09,PMC2738083,,,"A large outbreak of novel influenza A (H1N1) virus (swine origin influenza virus [S-OIV]) infection in Milwaukee, WI, occurred in late April 2009. We had recently developed a rapid multiplex reverse transcription-PCR enzyme hybridization assay (FluPlex) to determine the type (A or B) and subtype (H1, H2, H3, H5, H7, H9, N1 [human], N1 [animal], N2, or N7) of influenza viruses, and this assay was used to confirm the diagnoses for the first infected patients in the state. The analytical sensitivity was excellent at 1.5 to 116 copies/reaction, or 10(−3) to 10(−1) 50% tissue culture infective doses/ml. The testing of all existing hemagglutinin and neuraminidase subtypes of influenza A virus and influenza B virus (41 influenza virus strains) and 24 common respiratory pathogens showed only one low-level H3 cross-reaction with an H10N7 avian strain and only at 5.2 × 10(6) copies/reaction, not at lower concentrations. Comparisons of the FluPlex results with results from multiple validated in-house molecular assays, CDC-validated FDA-approved assays, and gene sequencing demonstrated 100% positive agreement for the typing of 179 influenza A viruses and 3 influenza B viruses, the subtyping of 110 H1N1 (S-OIV; N1 [animal]), 62 H1N1 (human), and 6 H3N2 (human) viruses, and the identification of 24 negative clinical samples and 100% negative agreement for all viruses tested except H1N1 (human) (97.7%). The small number of false-positive H1N1 (human) samples most likely represent increased sensitivity over that of other in-house assays, with four of four results confirmed by the CDC's influenza virus subtyping assay. The FluPlex is a rapid, inexpensive, sensitive, and specific method for the typing and subtyping of influenza viruses and demonstrated outstanding utility during the first 2 weeks of an S-OIV infection outbreak. Methods for rapid detection and broad subtyping of influenza viruses, including animal subtypes, are needed to address public concern over the emergence of pandemic strains. Attempts to automate this assay are ongoing.",,"['He, Jie', 'Bose, Michael E.', 'Beck, Eric T.', 'Fan, Jiang', 'Tiwari, Sagarika', 'Metallo, Jacob', 'Jurgens, Lisa A.', 'Kehl, Sue C.', 'Ledeboer, Nathan', 'Kumar, Swati', 'Weisburg, William', 'Henrickson, Kelly J.']",,,,
,PMC,Influenza A Virus Subtyping: Paradigm Shift in Influenza Diagnosis,http://dx.doi.org/10.1128/JCM.01388-09,PMC2738071,,,,,"['Vinikoor, Michael', 'Stevens, Jane', 'Nawrocki, John', 'Singh, Kamaljit']",,,,
,PMC,Overlapping Genes Produce Proteins with Unusual Sequence Properties and Offer Insight into De Novo Protein Creation,http://dx.doi.org/10.1128/JVI.00595-09,PMC2753099,,,"It is widely assumed that new proteins are created by duplication, fusion, or fission of existing coding sequences. Another mechanism of protein birth is provided by overlapping genes. They are created de novo by mutations within a coding sequence that lead to the expression of a novel protein in another reading frame, a process called “overprinting.” To investigate this mechanism, we have analyzed the sequences of the protein products of manually curated overlapping genes from 43 genera of unspliced RNA viruses infecting eukaryotes. Overlapping proteins have a sequence composition globally biased toward disorder-promoting amino acids and are predicted to contain significantly more structural disorder than nonoverlapping proteins. By analyzing the phylogenetic distribution of overlapping proteins, we were able to confirm that 17 of these had been created de novo and to study them individually. Most proteins created de novo are orphans (i.e., restricted to one species or genus). Almost all are accessory proteins that play a role in viral pathogenicity or spread, rather than proteins central to viral replication or structure. Most proteins created de novo are predicted to be fully disordered and have a highly unusual sequence composition. This suggests that some viral overlapping reading frames encoding hypothetical proteins with highly biased composition, often discarded as noncoding, might in fact encode proteins. Some proteins created de novo are predicted to be ordered, however, and whenever a three-dimensional structure of such a protein has been solved, it corresponds to a fold previously unobserved, suggesting that the study of these proteins could enhance our knowledge of protein space.",,"['Rancurel, Corinne', 'Khosravi, Mahvash', 'Dunker, A. Keith', 'Romero, Pedro R.', 'Karlin, David']",,,,
,PMC,Genetic and Pharmacologic Alteration of Cathepsin Expression Influences Reovirus Pathogenesis,http://dx.doi.org/10.1128/JVI.01095-09,PMC2748054,,,"The cathepsin family of endosomal proteases is required for proteolytic processing of several viruses during entry into host cells. Mammalian reoviruses utilize cathepsins B (Ctsb), L (Ctsl), and S (Ctss) for disassembly of the virus outer capsid and activation of the membrane penetration machinery. To determine whether cathepsins contribute to reovirus tropism, spread, and disease outcome, we infected 3-day-old wild-type (wt), Ctsb(−/−), Ctsl(−/−), and Ctss(−/−) mice with the virulent reovirus strain T3SA+. The survival rate of Ctsb(−/−) mice was enhanced in comparison to that of wt mice, whereas the survival rates of Ctsl(−/−) and Ctss(−/−) mice were diminished. Peak titers at sites of secondary replication in all strains of cathepsin-deficient mice were lower than those in wt mice. Clearance of the virus was delayed in Ctsl(−/−) and Ctss(−/−) mice in comparison to the levels for wt and Ctsb(−/−) mice, consistent with a defect in cell-mediated immunity in mice lacking cathepsin L or S. Cathepsin expression was dispensable for establishment of viremia, but cathepsin L was required for maximal reovirus growth in the brain. Treatment of wt mice with an inhibitor of cathepsin L led to amelioration of reovirus infection. Collectively, these data indicate that cathepsins B, L, and S influence reovirus pathogenesis and suggest that pharmacologic modulation of cathepsin activity diminishes reovirus disease severity.",,"['Johnson, Elizabeth M.', 'Doyle, Joshua D.', 'Wetzel, J. Denise', 'McClung, R. Paul', 'Katunuma, Nobuhiko', 'Chappell, James D.', 'Washington, M. Kay', 'Dermody, Terence S.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Nonstructural Protein 2 Interacts with a Host Protein Complex Involved in Mitochondrial Biogenesis and Intracellular Signaling,http://dx.doi.org/10.1128/JVI.00842-09,PMC2748024,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) generates 16 nonstructural proteins (nsp's) through proteolytic cleavage of a large precursor protein. Although several nsp's exhibit catalytic activities that are important for viral replication and transcription, other nsp's have less clearly defined roles during an infection. In order to gain a better understanding of their functions, we attempted to identify host proteins that interact with nsp's during SARS-CoV infections. For nsp2, we identified an interaction with two host proteins, prohibitin 1 (PHB1) and PHB2. Our results suggest that nsp2 may be involved in the disruption of intracellular host signaling during SARS-CoV infections.",,"['Cornillez-Ty, Cromwell T.', 'Liao, Lujian', 'Yates, John R.', 'Kuhn, Peter', 'Buchmeier, Michael J.']",,,,
,PMC,Avian Reovirus SigmaA Localizes to the Nucleolus and Enters the Nucleus by a Nonclassical Energy- and Carrier-Independent Pathway,http://dx.doi.org/10.1128/JVI.01080-09,PMC2747991,,,"Avian reovirus sigmaA is a double-stranded RNA (dsRNA)-binding protein that has been shown to stabilize viral core particles and to protect the virus against the antiviral action of interferon. To continue with the characterization of this viral protein, we have investigated its intracellular distribution in avian cells. Most sigmaA accumulates into cytoplasmic viral factories of infected cells, and yet a significant fraction was detected in the nucleolus. The protein also localizes in the nucleolus of transfected cells, suggesting that nucleolar targeting is not facilitated by the viral infection or by viral factors. Assays performed in both intact cells and digitonin-permeabilized cells demonstrate that sigmaA is able to enter the nucleus via a nucleoporin-dependent nondiffusional mechanism that does not require added cytosolic factors or energy input. These results indicate that sigmaA by itself is able to penetrate into the nucleus using a process that is mechanistically different from the classical nuclear localization signal/importin pathway. On the other hand, two sigmaA arginines that are necessary for dsRNA binding are also required for nucleolar localization, suggesting that dsRNA-binding and nucleolar targeting are intimately linked properties of the viral protein.",,"['Vázquez-Iglesias, Lorena', 'Lostalé-Seijo, Irene', 'Martínez-Costas, José', 'Benavente, Javier']",,,,
,PMC,Host-pathogen interactions during coronavirus infection of primary alveolar epithelial cells,http://dx.doi.org/10.1189/jlb.0209078,PMC2774885,,,"Viruses that infect the lung are a significant cause of morbidity and mortality in animals and humans worldwide. Coronaviruses are being associated increasingly with severe diseases in the lower respiratory tract. Alveolar epithelial cells are an important target for coronavirus infection in the lung, and infected cells can initiate innate immune responses to viral infection. In this overview, we describe in vitro models of highly differentiated alveolar epithelial cells that are currently being used to study the innate immune response to coronavirus infection. We have shown that rat coronavirus infection of rat alveolar type I epithelial cells in vitro induces expression of CXC chemokines, which may recruit and activate neutrophils. Although neutrophils are recruited early in infection in several coronavirus models including rat coronavirus. However, their role in viral clearance and/or immune-mediated tissue damage is not understood. Primary cultures of differentiated alveolar epithelial cells will be useful for identifying the interactions between coronaviruses and alveolar epithelial cells that influence the innate immune responses to infection in the lung. Understanding the molecular details of these interactions will be critical for the design of effective strategies to prevent and treat coronavirus infections in the lung.",,"['Miura, Tanya A.', 'Holmes, Kathryn V.']",,,,
,PMC,Darwinian selection for sites of Asn-linked glycosylation in phylogenetically disparate eukaryotes and viruses,http://dx.doi.org/10.1073/pnas.0905818106,PMC2726397,,,"Numerous protists and rare fungi have truncated Asn-linked glycan precursors and lack N-glycan-dependent quality control (QC) systems for glycoprotein folding in the endoplasmic reticulum. Here, we show that the abundance of sequons (NXT or NXS), which are sites for N-glycosylation of secreted and membrane proteins, varies by more than a factor of 4 among phylogenetically diverse eukaryotes, based on a few variables. There is positive correlation between the density of sequons and the AT content of coding regions, although no causality can be inferred. In contrast, there appears to be Darwinian selection for sequons containing Thr, but not Ser, in eukaryotes that have N-glycan-dependent QC systems. Selection for sequons with Thr, which nearly doubles the sequon density in human secreted and membrane proteins, occurs by an increased conditional probability that Asn and Thr are present in sequons rather than elsewhere. Increasing sequon densities of the hemagglutinin (HA) of influenza viruses A/H3N2 and A/H1N1 during the past few decades of human infection also result from an increased conditional probability that Asn, Thr, and Ser are present in sequons rather than elsewhere. In contrast, there is no selection on sequons by this mechanism in HA of A/H5N1 or 2009 A/H1N1 (Swine flu). Very strong selection for sequons with both Thr and Ser in glycoprotein of M(r) 120,000 (gp120) of HIV and related retroviruses results from this same mechanism, as well as amino acid composition bias and increases in AT content. We conclude that there is Darwinian selection for sequons in phylogenetically disparate eukaryotes and viruses.",,"['Cui, Jike', 'Smith, Temple', 'Robbins, Phillips W.', 'Samuelson, John']",,,,
,PMC,"Expression, crystallization and preliminary X-ray diffraction analysis of the N-terminal domain of nsp2 from avian infectious bronchitis virus",http://dx.doi.org/10.1107/S1744309109024749,PMC2720334,,,"Avian infectious bronchitis virus (IBV) is a prototype of the group III coronaviruses and encodes 15 nonstructural proteins which make up the transcription/replication machinery. The nsp2 protein from IBV has a unique and novel sequence and has no experimentally confirmed function in replication, whereas it has been proposed to be crucial for early viral infection and may inhibit the early host immune response. The gene that encodes a double-mutant IBV nsp2 N-terminal domain (residues 9–393 of the polyprotein, with mutations Q132L and L270F) was cloned and expressed in Escherichia coli and the protein was subjected to crystallization trials. The crystals diffracted to 2.5 Å resolution and belonged to space group P6(2) or P6(4), with unit-cell parameters a = b = 114.2, c = 61.0 Å, α = β = 90, γ = 120°. Each asymmetric unit contained one molecule.",,"['Yang, Anqi', 'Wei, Lei', 'Zhao, Weiran', 'Xu, Yuanyuan', 'Rao, Zihe']",,,,
,PMC,Triplex structures in an RNA pseudoknot enhance mechanical stability and increase efficiency of –1 ribosomal frameshifting,http://dx.doi.org/10.1073/pnas.0905046106,PMC2722267,,,"Many viruses use programmed –1 ribosomal frameshifting to express defined ratios of structural and enzymatic proteins. Pseudoknot structures in messenger RNAs stimulate frameshifting in upstream slippery sequences. The detailed molecular determinants of pseudoknot mechanical stability and frameshifting efficiency are not well understood. Here we use single-molecule unfolding studies by optical tweezers, and frameshifting assays to elucidate how mechanical stability of a pseudoknot and its frameshifting efficiency are regulated by tertiary stem-loop interactions. Mechanical unfolding of a model pseudoknot and mutants designed to dissect specific interactions reveals that mechanical stability depends strongly on triplex structures formed by stem-loop interactions. Combining single-molecule and mutational studies facilitates the identification of pseudoknot folding intermediates. Average unfolding forces of the pseudoknot and mutants ranging from 50 to 22 picoNewtons correlated with frameshifting efficiencies ranging from 53% to 0%. Formation of major-groove and minor-groove triplex structures enhances pseudoknot stem stability and torsional resistance, and may thereby stimulate frameshifting. Better understanding of the molecular determinants of frameshifting efficiency may facilitate the development of anti-virus therapeutics targeting frameshifting.",,"['Chen, Gang', 'Chang, Kung-Yao', 'Chou, Ming-Yuan', 'Bustamante, Carlos', 'Tinoco, Ignacio']",,,,
,PMC,Performance of the RealStar Chikungunya Virus Real-Time Reverse Transcription-PCR Kit,http://dx.doi.org/10.1128/JCM.01024-09,PMC2738119,,,A novel commercial Chikungunya virus real-time reverse transcription-PCR (RT-PCR) kit was evaluated on a comprehensive panel of original patient samples. The assay was 100% sensitive and specific in comparison to a published real-time RT-PCR. Viral loads from both assays were highly correlated. The kit proved to be suitable for routine use in patient care.,,"['Panning, Marcus', 'Hess, Markus', 'Fischer, Waldemar', 'Grywna, Klaus', 'Pfeffer, Martin', 'Drosten, Christian']",,,,
,PMC,Prevalence and Clinical Characterization of a Newly Identified Human Rhinovirus C Species in Children with Acute Respiratory Tract Infections,http://dx.doi.org/10.1128/JCM.00745-09,PMC2738104,,,"Human rhinovirus C (HRV-C) is a newly identified genotype of HRV found in patients with respiratory tract infections (RTIs); however, its epidemiological profile and clinical characteristics are not well understood. In this study, Chinese children with RTIs were screened for HRV-C and their epidemiological and clinical characteristics were analyzed. From December 2006 to November 2007, 406 nasopharyngeal aspirates from children younger than 14 years of age with RTIs were screened for HRV and other common respiratory viruses by PCR or reverse transcription-PCR. Two-hundred twenty-four (55.2%) of the specimens were infected with at least one virus, including 53 patients with HRV (13%). HRV-A, HRV-B, and HRV-C were detected in 22, 12, and 19 specimens, respectively. HRV-C was detected mainly from December 2006 to April 2007 and from October to November 2007, with peaks in December and April (10/19). Acute upper respiratory infection and bronchopneumonia were observed in 53 and 37% of the cases, respectively. The most common symptoms were cough (82%), runny nose (53%), and fever (37%). Wheezing and bronchiolitis were less common in patients infected with HRV-C than in those infected with respiratory syncytial virus (RSV). Partial sequencing of the genes coding for VP4 and VP2 revealed that the HRV-C strains were 56 to 62% identical at the amino acid level to HRV-B and HRV-A reference strains and 80 to 99% identical to HRV-C reference strains. In conclusion, HRV-C is an important cause of RTIs in children, and highly diversified strains of HRV-C are prevalent in China. HRV-C may produce different epidemiological features, and patients infected with HRV-C may exhibit different clinical features from patients infected with RSV or HRV-A/B.",,"['Jin, Yu', 'Yuan, Xin-Hui', 'Xie, Zhi-Ping', 'Gao, Han-Chun', 'Song, Jing-Rong', 'Zhang, Rong-Fang', 'Xu, Zi-Qian', 'Zheng, Li-Shu', 'Hou, Yun-De', 'Duan, Zhao-Jun']",,,,
,PMC,Evolution of Teleost Fish Retroviruses: Characterization of New Retroviruses with Cellular Genes,http://dx.doi.org/10.1128/JVI.02546-08,PMC2748043,,,"The interactions between retroviruses and their hosts can be of a beneficial or detrimental nature. Some endogenous retroviruses are involved in development, while others cause disease. The Genome Parsing Suite (GPS) is a software tool to track and trace all Retroid agents in any sequenced genome (M. A. McClure et al., Genomics 85:512-523, 2005). Using the GPS, the retroviral content was assessed in four model teleost fish. Eleven new species of fish retroviruses are identified and characterized. The reverse transcriptase protein sequences were used to reconstruct a fish retrovirus phylogeny, thereby, significantly expanding the epsilonretrovirus family. Most of these novel retroviruses encode additional genes, some of which are homologous to cellular genes that would confer viral advantage. Although the fish divergence is much more ancient, retroviruses began infecting fish genomes approximately 4 million years ago.",,"['Basta, Holly A.', 'Cleveland, Sean B.', 'Clinton, Rochelle A.', 'Dimitrov, Alexander G.', 'McClure, Marcella A.']",,,,
,PMC,Identification of a Unique “Stability Control Region” that Controls Protein Stability of Tropomyosin: A Two-Stranded α-Helical Coiled-Coil,http://dx.doi.org/10.1016/j.jmb.2009.07.039,PMC2756485,,,"Nine recombinant chicken skeletal α-tropomyosin proteins were prepared, eight C-terminal deletion constructs and the full length protein (1–81, 1–92, 1–99, 1–105, 1–110, 1–119, 1–131, 1–260 and 1–284) and characterized by circular dichroism spectroscopy and analytical ultracentrifugation. We identified for the first time, a stability control region between residues 97 and 118. Fragments of tropomyosin lacking this region (1–81, 1–92, and 1–99) still fold into two-stranded α-helical coiled-coils but are significantly less stable (T(m) between 26–28.5°C) than longer fragments containing this region (1–119, 1–131, 1–260 and 1–284) which show a large increase in their thermal midpoints (T(m) between 40–43°C) for a ΔT(m) of 16°C between 1–99 and 1–119. We further investigated two additional fragments which ended between residues 99 and 119, that is fragments 1–105 and 1–110. These fragments were more stable than 1–99 and less stable than 1–119 and showed that there were three separate sites that synergistically contribute to the large jump in protein stability (two electrostatic clusters, 97–104 and 112–118 and one hydrophobic interaction from Leu 110. All the residues involved in these stabilizing interactions are located outside the hydrophobic core a and d positions which have been shown to be the major contributor to coiled-coil stability. Our results clearly show that protein stability is more complex than previously thought and unique sites can synergistically control protein stability over long distances.",,"['Hodges, Robert S.', 'Mills, Janine', 'McReynolds, Susanna', 'Kirwan, J. Paul', 'Tripet, Brian', 'Osguthorpe, David']",,,,
,PMC,Development of a Cell-Based Hepatitis C Virus Infection Fluorescent Resonance Energy Transfer Assay for High-Throughput Antiviral Compound Screening,http://dx.doi.org/10.1128/AAC.00495-09,PMC2764155,,,"A major obstacle in the treatment of chronic hepatitis C virus (HCV) infection has been the lack of effective, well-tolerated therapeutics. Notably, the recent development of the HCV cell culture infection system now allows not only for the study of the entire viral life cycle, but also for the screening of inhibitors against all aspects of HCV infection. However, in order to screen libraries of potential antiviral compounds, it is necessary to develop a highly reproducible, accurate assay for HCV infection adaptable for high-throughput screening (HTS) automation. Using an internally quenched 5-FAM/QXL 520 fluorescence resonance energy transfer (FRET) substrate containing the HCV NS3 peptide cleavage sequence, we report the development of a simple, mix-and-measure, homogenous, cell-based HCV infection assay amendable for HTS. This assay makes use of synchronized, nondividing human hepatoma-derived Huh7 cells, which support more-reproducible long-term HCV infection and can be readily scaled down to a 96-well-plate format. We demonstrate that this stable cell culture method eliminates common problems associated with standard cell-based HTS, such as cell culture variability, poor reproducibility, and low signal intensity. Importantly, this HCV FRET assay not only can identify inhibitors that act throughout the viral life cycle as effectively as more-standard HCV assays, such as real-time quantitative PCR and Western blot analysis, but also exhibits a high degree of accuracy with limited signal variation (i.e., Z′ ≥ 0.6), providing the basis for a robust HTS campaign for screening compound libraries and identifying novel HCV antivirals.",,"['Yu, Xuemei', 'Sainz, Bruno', 'Uprichard, Susan L.']",,,,
,PMC,Detailed Mechanistic Insights into HIV-1 Sensitivity to Three Generations of Fusion Inhibitors,http://dx.doi.org/10.1074/jbc.M109.004416,PMC2785381,,,"Peptides based on the second heptad repeat (HR2) of viral class I fusion proteins are effective inhibitors of virus entry. One such fusion inhibitor has been approved for treatment of human immunodeficiency virus-1 (T20, enfuvirtide). Resistance to T20 usually maps to the peptide binding site in HR1. To better understand fusion inhibitor potency and resistance, we combined virological, computational, and biophysical experiments with comprehensive mutational analyses and tested resistance to T20 and second and third generation inhibitors (T1249 and T2635). We found that most amino acid substitutions caused resistance to the first generation peptide T20. Only charged amino acids caused resistance to T1249, and none caused resistance to T2635. Depending on the drug, we can distinguish four mechanisms of drug resistance: reduced contact, steric obstruction, electrostatic repulsion, and electrostatic attraction. Implications for the design of novel antiviral peptide inhibitors are discussed.",,"['Eggink, Dirk', 'Langedijk, Johannes P. M.', 'Bonvin, Alexandre M. J. J.', 'Deng, Yiqun', 'Lu, Min', 'Berkhout, Ben', 'Sanders, Rogier W.']",,,,
,PMC,Targeted Delivery of Anti-coxsackievirus siRNAs Using Ligand-conjugated Packaging RNAs,http://dx.doi.org/10.1016/j.antiviral.2009.07.005,PMC3909712,,,"Coxsackievirus B3 (CVB3) is a common pathogen of myocarditis. We previously synthesized a siRNA targeting the CVB3 protease 2A (siRNA/2A) gene and achieved reduction of CVB3 replication by 92% in vitro. However, like other drugs under development, CVB3 siRNA faces a major challenge of targeted delivery. In this study, we investigated a novel approach to deliver CVB3 siRNAs to a specific cell population (e.g. HeLa cells containing folate receptor) using receptor ligand (folate)-linked packaging RNA (pRNA) from bacterial phage phi29. pRNA monomers can spontaneously form dimers and multimers under optimal conditions by base-pairing between their stem loops. By covalently linking a fluorescence-tag to folate, we delivered the conjugate specifically to HeLa cells without the need of transfection. We further demonstrated that pRNA covalently conjugated to siRNA/2A achieved an equivalent antiviral effect to that of the siRNA/2A alone. Finally, the drug targeted delivery was further evaluated by using pRNA monomers or dimers, which carried both the siRNA/2A and folate ligand and demonstrated that both of them strongly inhibited CVB3 replication. These data indicate that pRNA as a siRNA carrier can specifically deliver the drug to target cells via its ligand and specific receptor interaction and inhibit virus replication effectively.",,"['Zhang, Huifang M.', 'Su, Yue', 'Guo, Songchuan', 'Yuan, Ji', 'Lim, Travis', 'Liu, Jing', 'Guo, Peixuan', 'Yang, Decheng']",,,,
,PMC,A Habitat-Based Model for the Spread of Hantavirus Between Reservoir and Spillover Species,http://dx.doi.org/10.1016/j.jtbi.2009.07.009,PMC2746865,,,"New habitat-based models for spread of hantavirus are developed which account for interspecies interaction. Existing habitat-based models do not consider interspecies pathogen transmission, a primary route for emergence of new infectious diseases and reservoirs in wildlife and man. The modeling of interspecies transmission has the potential to provide more accurate predictions of disease persistence and emergence dynamics. The new models are motivated by our recent work on hantavirus in rodent communities in Paraguay. Our Paraguayan data illustrate the spatial and temporal overlap among rodent species, one of which is the reservoir species for Jabora virus and others which are spillover species. Disease transmission occurs when their habitats overlap. Two mathematical models, a system of ordinary differential equations (ODE) and a continuous-time Markov chain (CTMC) model, are developed for spread of hantavirus between a reservoir and a spillover species. Analysis of a special case of the ODE model provides an explicit expression for the basic reproduction number, ℛ(0), such that if ℛ(0) < 1, then the pathogen does not persist in either population but if ℛ(0) > 1, pathogen outbreaks or persistence may occur. Numerical simulations of the CTMC model display sporadic disease incidence, a new behavior of our habitat-based model, not present in other models, but which is a prominent feature of the seroprevalence data from Paraguay. Environmental changes that result in greater habitat overlap result in more encounters among various species that may lead to pathogen outbreaks and pathogen establishment in a new host.",,"['Allen, Linda J. S.', 'Wesley, Curtis L.', 'Owen, Robert D.', 'Goodin, Douglas G.', 'Koch, David', 'Jonsson, Colleen B.', 'Chu, Yong-Kyu', 'Shawn Hutchinson, J. M.', 'Paige, Robert L.']",,,,
,PMC,Recommendations for Modeling Disaster Responses in Public Health and Medicine: A Position Paper of The Society for Medical Decision Making,http://dx.doi.org/10.1177/0272989X09340346,PMC3699691,,,"PURPOSE: Mathematical and simulation models are increasingly used to plan for and evaluate health sector responses to disasters, yet no clear consensus exists regarding best practices for the design, conduct, and reporting of such models. We examined a large selection of published health sector disaster response models to generate a set of best practice guidelines for such models. METHODS: We reviewed a spectrum of published disaster response models addressing public health or healthcare delivery, focusing in particular on the type of disaster and response decisions considered, decision makers targeted, choice of outcomes evaluated, modeling methodology, and reporting format. We developed initial recommendations for best practices for creating and reporting such models and refined these guidelines after soliciting feedback from response modeling experts and from members of the Society for Medical Decision Making. RESULTS: We propose six recommendations for model construction and reporting, inspired by the most exemplary models: Health sector disaster response models should address real-world problems; be designed for maximum usability by response planners; strike the appropriate balance between simplicity and complexity; include appropriate outcomes, which extend beyond those considered in traditional cost-effectiveness analyses; and be designed to evaluate the many uncertainties inherent in disaster response. Finally, good model reporting is particularly critical for disaster response models. CONCLUSIONS: Quantitative models are critical tools for planning effective health sector responses to disasters. The recommendations we propose can increase the applicability and interpretability of future models, thereby improving strategic, tactical, and operational aspects of preparedness planning and response.",,"['Brandeau, Margaret L.', 'McCoy, Jessica H.', 'Hupert, Nathaniel', 'Holty, Jon-Erik', 'Bravata, Dena M.']",,,,
,PMC,Functions of the cytoplasmic RNA sensors RIG-I and MDA-5: Key regulators of innate immunity,http://dx.doi.org/10.1016/j.pharmthera.2009.06.012,PMC3165056,,,"The innate immune system responds within minutes of infection to produce type I interferons and pro-inflammatory cytokines. Interferons induce the synthesis of cell proteins with antiviral activity, and also shape the adaptive immune response by priming T cells. Despite the discovery of interferons over 50 years ago, only recently have we begun to understand how cells sense the presence of a virus infection. Two families of pattern recognition receptors have been shown to distinguish unique molecules present in pathogens, such as bacterial and fungal cell wall components, viral RNA and DNA, and lipoproteins. The first family includes the membrane-bound toll-like receptors (TLRs). Studies of the signaling pathways that lead from pattern recognition to cytokine induction have revealed extensive and overlapping cascades that involve protein-protein interactions and phosphorylation, and culminate in activation of transcription proteins that control the transcription of genes encoding interferons and other cytokines. A second family of pattern recognition receptors has recently been identified, which comprises the cytoplasmic sensors of viral nucleic acids, including MDA-5, RIG-I, and LGP2. In this review we summarize the discovery of these cytoplasmic sensors, how they recognize nucleic acids, the signaling pathways leading to cytokine synthesis, and viral countermeasures that have evolved to antagonize the functions of these proteins. We also consider the function of these cytoplasmic sensors in apoptosis, development and differentiation, and diabetes.",,"['Barral, Paola M', 'Sarkar, Devanand', 'Su, Zao-zhong', 'Barber, Glen N.', 'DeSalle, Rob', 'Racaniello, Vincent R', 'Fisher, Paul B.']",,,,
,PMC,Is multiple sclerosis a mitochondrial disease?,http://dx.doi.org/10.1016/j.bbadis.2009.07.002,PMC2790545,,,"Multiple sclerosis (MS) is a relatively common and etiologically unknown disease with no cure treatment. It is the leading cause of neurological disability in young adults, affecting over two million people worldwide. Traditionally, MS has been considered a chronic, inflammatory disorder of the central white matter in which ensuing demyelination results in physical disability. Recently, MS has become increasingly viewed as a neurodegenerative disorder in which axonal injury, neuronal loss, and atrophy of the central nervous system lead to permanent neurological and clinical disability. In this article, we discuss the latest developments on MS research, including etiology, pathology, genetic association, EAE animal models, mechanisms of neuronal injury and axonal transport and therapeutics. In this article, we also focus on the mechanisms of mitochondrial dysfunction that are involved in MS, including mitochondrial DNA defects, and mitochondrial structural/functional changes.",,"['Mao, Peizhong', 'Reddy, P. Hemachandra']",,,,
,PMC,Knowledge about pandemic influenza and compliance with containment measures among Australians,http://dx.doi.org/10.2471/BLT.08.060772,PMC2733278,,,"OBJECTIVE: To examine the level of stated compliance with public health pandemic influenza control measures and explore factors influencing cooperation for pandemic influenza control in Australia. METHODS: A computer-assisted telephone interview survey was conducted by professional interviewers to collect information on the Australian public’s knowledge of pandemic influenza and willingness to comply with public health control measures. The sample was randomly selected using an electronic database and printed telephone directories to ensure sample representativeness from all Australian states and territories. After we described pandemic influenza to the respondents to ensure they understood the significance of the issue, the questions on compliance were repeated and changes in responses were analysed with McNemar’s test for paired data. FINDINGS: Only 23% of the 1166 respondents demonstrated a clear understanding of the term “pandemic influenza”. Of those interviewed, 94.1% reported being willing to comply with home quarantine; 94.2%, to avoid public events; and 90.7%, to postpone social gatherings. After we explained the meaning of “pandemic” to interviewees, stated compliance increased significantly (to 97.5%, 98.3% and 97.2% respectively). Those who reported being unfamiliar with the term “pandemic influenza,” male respondents and employed people not able to work from home were less willing to comply. CONCLUSION: In Australia, should the threat arise, compliance with containment measures against pandemic influenza is likely to be high, yet it could be further enhanced through a public education programme conveying just a few key messages. A basic understanding of pandemic influenza is associated with stated willingness to comply with containment measures. Investing now in promoting measures to prepare for a pandemic or other health emergency will have considerable value.",,"['Eastwood, Keith', 'Durrheim, David', 'Francis, J Lynn', 'd’Espaignet, Edouard Tursan', 'Duncan, Sarah', 'Islam, Fakhrul', 'Speare, Rick']",,,,
,PMC,Vesicular Stomatitis Virus as a Novel Cancer Vaccine Vector to Prime Antitumor Immunity Amenable to Rapid Boosting With Adenovirus,http://dx.doi.org/10.1038/mt.2009.154,PMC2835010,,,"Vesicular stomatitis virus (VSV) has proven to be an effective vaccine vector for immunization against viral infection, but its potential to induce an immune response to a self-tumor antigen has not been investigated. We constructed a recombinant VSV expressing human dopachrome tautomerase (hDCT) and evaluated its immunogenicity in a murine melanoma model. Intranasal delivery of VSV-hDCT activated both CD4(+) and CD8(+) DCT-specific T-cell responses. The magnitude of these responses could be significantly increased by booster immunization with recombinant adenovirus (Ad)-hDCT, which led to enhanced efficacy against B16-F10 melanoma in both prophylactic and therapeutic settings. Notably, the interval of VSV/Ad heterologous vaccination could be shortened to as few as 4 days, making it a potential regimen to rapidly expand antigen-specific effector cells. Furthermore, VSV-hDCT could increase DCT-specific T-cell responses primed by Ad-hDCT, suggesting VSV is efficient for both priming and boosting of the immune response against a self-tumor antigen.",,"['Bridle, Byram W', 'Boudreau, Jeanette E', 'Lichty, Brian D', 'Brunellière, Jérôme', 'Stephenson, Kyle', 'Koshy, Sandeep', 'Bramson, Jonathan L', 'Wan, Yonghong']",,,,
,PMC,Oxidative Stress Enhances Toll-Like Receptor 3 Response to Double-Stranded RNA in Airway Epithelial Cells,http://dx.doi.org/10.1165/rcmb.2008-0345OC,PMC2891495,,,"Virus infections are a major cause of chronic obstructive pulmonary disease (COPD) exacerbations. Recently, Toll-like receptor 3 (TLR3) has been demonstrated to react to double-stranded RNA (dsRNA) and to be involved in the immune responses after viral infections. In the present study, we examined whether oxidative stress, which is involved in the pathogenesis of COPD, enhances the responses of TLR3 in airway epithelial cells. The effect of hydrogen peroxide (H(2)O(2)) on the release of IL-8 from BEAS-2B cells and primary human bronchial epithelial cells after stimulation with polyinosine-polycytidylic acid [poly(I:C)], a synthetic analog of viral dsRNA and a ligand for TLR3, and the signal transduction were examined. One hundred to 150 μM H(2)O(2) significantly potentiated the release of IL-8 from the epithelial cells after stimulation with 10 μg/ml poly(I:C). The H(2)O(2)-augmented IL-8 release was inhibited by treatment with N-acetylcysteine. One hundred micromoles of H(2)O(2) enhanced the translocation of nuclear factor (NF)-κB p65, but not that of interferon regulatory factor-3 (IRF-3), into the nucleus and the NF-κB DNA binding activity after poly(I:C) stimulation, which effect was inhibited not by the silencing of IRF-3 but by MG132, a proteasome inhibitor, or dexamethasone. One hundred micromoles of H(2)O(2) potentiated the TLR3 expression on the airway epithelial cells treated with poly(I:C). These data suggest that oxidative stress augments the response of TLR3 in airway epithelial cells via NF-κB and that this effect might be partly mediated by the enhancement of TLR3 expression. Modulation of this pathway may be a therapeutic target for viral-induced exacerbations of COPD.",,"['Koarai, Akira', 'Sugiura, Hisatoshi', 'Yanagisawa, Satoru', 'Ichikawa, Tomohiro', 'Minakata, Yoshiaki', 'Matsunaga, Kazuto', 'Hirano, Tsunahiko', 'Akamatsu, Keiichiro', 'Ichinose, Masakazu']",,,,
,PMC,Diminished Intracellular Invariant Chain Expression Following Vaccinia Virus Infection,http://dx.doi.org/10.4049/jimmunol.0802741,PMC2844081,,,"Vaccinia virus (VV) has been used as a vaccine to eradicate smallpox and as a vaccine for HIV and tumors. However, the immunoevasive properties of VV, have raised safety concerns. VV infection of APC perturbs MHC class II-mediated Ag presentation. Exposure of human B cell lines to VV induced a dramatic reduction in cellular expression of the class II chaperone, invariant chain (Ii) during the late stages (i.e. 8–10 h) of infection. Yet, cell viability and surface expression of MHC class II molecules were maintained up to 24 h after exposure to virus. Reductions in Ii and class II mRNA levels were detected as early as 6 h after VV infection of APC. To examine whether VV was acting solely to disrupt host protein synthesis, B cells were treated with an inhibitor of translation, cycloheximide (CHX). Within 1 h of B cell CHX treatment, Ii protein expression decreased coupled with a loss of class II presentation. Analysis of Ii degradation in VV or CHX treated cells, revealed on-going Ii proteolysis contributing to reduced steady state Ii levels in these APC. Yet in contrast with CHX, VV infection of APC altered lysosomal protease expression and Ii degradation. Virus infection induced cellular cathepsin L expression while reducing the levels of other lysosomal proteases. These results demonstrate that at late stages of VV infection, reductions in cellular Ii levels coupled with changes in lysosomal protease activity, contribute in part to defects in class II presentation.",,"['Wang, Nan', 'Weber, Ekkehard', 'Blum, Janice S.']",,,,
,PMC,Functional characterization of mouse spinal cord infiltrating CD8+ lymphocytes,http://dx.doi.org/10.1016/j.jneuroim.2009.06.013,PMC3178656,,,"Understanding the immunopathogenesis of neuroimmunological diseases of the CNS requires a robust method for isolating and characterizing the immune effector cells that infiltrate the spinal cord in animal models. We have developed a simple and rapid isolation method that produces high yields of spinal cord infiltrating leukocytes from a single demyelinated spinal cord and which maintains high surface expression of key immunophenotyping antigens. Using this method and the Theiler’s virus model of chronic demyelination, we report the presence of spinal cord infiltrating acute effector CD8(+) lymphocytes that are CD45(hi)CD44(lo)CD62L(−) and a population of spinal cord infiltrating target effector memory CD8(+) lymphocytes that are CD45(hi)CD44(hi)CD62L(−). These cells respond robustly to ex vivo stimulation by producing interferon γ but do not exhibit specificity for Theiler’s virus in a cytotoxicity assay. We conclude that target-derived lymphocytes in a mouse model of chronic spinal cord demyelination may have unique functional specificities.",,"['Deb, Chandra', 'Howe, Charles L']",,,,
,PMC,The Porcine Reproductive and Respiratory Syndrome Virus nsp2 Cysteine Protease Domain Possesses both trans- and cis-Cleavage Activities,http://dx.doi.org/10.1128/JVI.00834-09,PMC2738230,,,"The N terminus of the replicase nonstructural protein 2 (nsp2) of porcine reproductive and respiratory syndrome virus (PRRSV) contains a putative cysteine protease domain (PL2). Previously, we demonstrated that deletion of either the PL2 core domain (amino acids [aa] 47 to 180) or the immediate downstream region (aa 181 to 323) is lethal to the virus. In this study, the PL2 domain was found to encode an active enzyme that mediates efficient processing of nsp2-3 in CHO cells. The PL2 protease possessed both trans- and cis-cleavage activities, which were distinguished by individual point mutations in the protease domain. The minimal size required to maintain these two enzymatic activities included nsp2 aa 47 to 240 (Tyr(47) to Cys(240)) and aa 47 to 323 (Tyr(47) to Leu(323)), respectively. Introduction of targeted amino acid mutations in the protease domain confirmed the importance of the putative Cys(55)- His(124) catalytic motif for nsp2/3 proteolysis in vitro, as were three additional conserved cysteine residues (Cys(111), Cys(142), and Cys(147)). The conserved aspartic acids (e.g., Asp(89)) were essential for the PL2 protease trans-cleavage activity. Reverse genetics revealed that the PL2 trans-cleavage activity played an important role in the PRRSV replication cycle in that mutations that impaired the PL2 protease trans function, but not the cis activity, were detrimental to viral viability. Lastly, the potential nsp2/3 cleavage site was probed. Mutations with the largest impact on in vitro cleavage were at or near the G(1196)|G(1197) dipeptide.",,"['Han, Jun', 'Rutherford, Mark S.', 'Faaberg, Kay S.']",,,,
,PMC,Drug Delivery–mediated Control of RNA Immunostimulation,http://dx.doi.org/10.1038/mt.2009.147,PMC2835254,,,"RNA interference (RNAi) has generated significant interest as a strategy to suppress viral infection, but in some cases antiviral activity of unmodified short-interfering RNA (siRNA) has been attributed to activation of innate immune responses. We hypothesized that immunostimulation by unmodified siRNA could mediate both RNAi as well as innate immune stimulation depending on the mode of drug delivery. We investigated the potential of immunostimulatory RNAs (isRNAs) to suppress influenza A virus in vivo in the mouse lung. Lipidoid 98N12-5(1) formulated with unmodified siRNA targeting the influenza nucleoprotein gene exhibited antiviral activity. Formulations were optimized to increase antiviral activity, but the antiviral activity of lipidoid-delivered siRNA did not depend on sequence homology to the influenza genome as siRNA directed against unrelated targets also suppressed influenza replication in vivo. This activity was primarily attributed to enhancement of innate immune stimulation by lipidoid-mediated delivery, which indicates increased toll-like receptor (TLR) activation by siRNA. Certain chemical modifications to the siRNA backbone, which block TLR7/8 activation but retain in vitro RNAi activity, prevented siRNA-mediated antiviral activity despite enhanced lipidoid-mediated delivery. Here, we demonstrate that innate immune activation caused by unmodified siRNA can have therapeutically relevant effects, and that these non-RNAi effects can be controlled through chemical modifications and drug delivery.",,"['Nguyen, David N.', 'Chen, Steve C-Y', 'Lu, James', 'Goldberg, Michael', 'Kim, Phillip', 'Sprague, Andrew', 'Novobrantseva, Tatiana', 'Sherman, Jennifer', 'Shulga-Morskaya, Svetlana', 'de Fougerolles, Antonin', 'Chen, Jianzhu', 'Langer, Robert', 'Anderson, Daniel G']",,,,
,PMC,Human Rhinovirus C Associated with Wheezing in Hospitalized Children in the Middle East,http://dx.doi.org/10.1016/j.jcv.2009.06.007,PMC2759319,,,"BACKGROUND: Few studies have investigated the disease burden and genetic diversity of human rhinoviruses (HRV) in developing countries. OBJECTIVES: To assess the burden of HRV in Amman, Jordan and to characterize clinical differences between HRV groups. STUDY DESIGN: We prospectively studied children <5 years old hospitalized with respiratory symptoms and/or fever in Amman, Jordan. Viruses were identified by real-time RT-PCR. VP4/VP2 gene sequencing was performed on HRV-positive specimens. RESULTS: Of 728 enrolled children, 266 (37%) tested positive for picornaviruses, 240 of which were HRV. Of the HRV-positive samples, 62 (26%) were of the recently identified group HRVC, 131 (55%) were HRVA, and 7 (3%) were HRVB. The HRVC strains clustered into at least 19 distinct genotypes. Compared with HRVA-infected children, children with HRVC were more likely to require supplemental oxygen (63% vs. 42%, p=0.007) and, when co-infections were excluded, were more likely to have wheezing (100% vs. 82%, p=0.016). CONCLUSIONS: There is a significant burden of HRV-associated hospitalizations in young children in Jordan. Infection with the recently identified group HRVC is associated with wheezing and more severe illness.",,"['Miller, E. Kathryn', 'Khuri-Bulos, Najwa', 'Williams, John V.', 'Shehabi, Asem A.', 'Faouri, Samir', 'Jundi, Ihsan Al', 'Chen, Qingxia', 'Heil, Luke', 'Mohamed, Yassir', 'Morin, Laura-Lee', 'Ali, Asad', 'Halasa, Natasha B.']",,,,
,PMC,"Public perceptions, anxiety, and behaviour change in relation to the swine flu outbreak: cross sectional telephone survey",http://dx.doi.org/10.1136/bmj.b2651,PMC2714687,19574308,CC BY-NC,"Objective To assess whether perceptions of the swine flu outbreak predicted changes in behaviour among members of the public in England, Scotland, and Wales. Design Cross sectional telephone survey using random digit dialling. Setting Interviews by telephone between 8 and 12 May. Participants 997 adults aged 18 or more who had heard of swine flu and spoke English. Main outcome measures Recommended change in behaviour (increases in handwashing and surface cleaning or plans made with a “flu friend”) and avoidance behaviours (engaged in one or more of six behaviours such as avoiding large crowds or public transport). Results 37.8% of participants (n=377) reported performing any recommended behaviour change “over the past four days . . . because of swine flu.” 4.9% (n=49) had carried out any avoidance behaviour. Controlling for personal details and anxiety, recommended changes were associated with perceptions that swine flu is severe, that the risk of catching it is high risk, that the outbreak will continue for a long time, that the authorities can be trusted, that good information has been provided, that people can control their risk of catching swine flu, and that specific behaviours are effective in reducing the risk. Being uncertain about the outbreak and believing that the outbreak had been exaggerated were associated with a lower likelihood of change. The strongest predictor of behaviour change was ethnicity, with participants from ethnic minority groups being more likely to make recommended changes (odds ratio 3.2, 95% confidence interval 2.0 to 5.3) and carry out avoidance behaviours (4.1, 2.0 to 8.4). Conclusions The results support efforts to inform the public about specific actions that can reduce the risks from swine flu and to communicate about the government’s plans and resources. Tackling the perception that the outbreak has been “over-hyped” may be difficult but worthwhile. Additional research is required into differing reactions to the outbreak among ethnic groups.",2009 Jul 2,"['Rubin, G James', 'Amlôt, Richard', 'Page, Lisa', 'Wessely, Simon']",BMJ,,,
,PMC,Responsibility as an Ethical Framework for Public Health Interventions,http://dx.doi.org/10.2105/AJPH.2007.127514,PMC2696664,,,"Bioethical debate has been characterized from the beginning by the central importance placed on autonomy. This is because bioethics has, until now, been concerned with the relationship between doctor and patient in a clinical context or, alternatively, with the rights of individuals involved in biomedical research. The increased involvement of bioethics in the domain of public health, however, makes it necessary to refer to other principles and values, thus shaping a new responsibility-focused bioethics that extends itself beyond the early boundaries of this discipline.",,"Turoldo, Fabrizio",,,,
,PMC,Reading chest radiographs in the critically ill (Part II): Radiography of lung pathologies common in the ICU patient,http://dx.doi.org/10.4103/1817-1737.53349,PMC2714572,19641649,CC BY,This is part II of two series review of reading chest radiographs in the critically ill. Conventional chest radiography remains the cornerstone of day to day management of the critically ill occasionally supplemented by computed tomography or ultrasound for specific indications. In this second review we discuss radiographic findings of cardiopulmonary disorders common in the intensive care patient and suggest guidelines for interpretation based not only on imaging but also on the pathophysiology and clinical grounds.,2009 Jul-Sep,"['Khan, Ali Nawaz', 'Al-Jahdali, Hamdan', 'AL-Ghanem, Sarah', 'Gouda, Alaa']",Ann Thorac Med,,,
,PMC,Emerging and re-emerging viruses in the era of globalisation,http://dx.doi.org/10.2450/2009.0076-08,PMC2719266,,,,,"['Zappa, Alessandra', 'Amendola, Antonella', 'Romanò, Luisa', 'Zanetti, Alessandro']",,,,
,PMC,Vaccine efficacy against Ontario isolates of infectious bronchitis virus,,PMC2705076,,,Infectious bronchitis (IB) is an economically important viral disease with worldwide distribution. Every country with an intensive poultry industry has infectious bronchitis virus (IBV). The virus rapidly spreads from bird to bird through horizontal transmission by aerosol or ingestion. Sentinel bird studies were carried out in southern Ontario and IBV has been isolated from layer flocks. Genetic analysis of the S1 region of the strains showed that they were not vaccine related. The pathogenicity of selected Ontario variants of IBV isolates was studied and the subsequent work was to determine the degree of protection against field isolates provided by a commonly used vaccine MILDVAC-Ma5 in Ontario. The protection was evaluated by challenging immunized chickens with the respiratory (IBV-ON1) and nephropathogenic (IBV-ON4) viruses. The mean vaccine efficacy for IBV-ON1 was 66.7% indicating that a Massachusetts serotype vaccine would provide some protection against IBV field isolates.,,"['Grgić, Helena', 'Hunter, D. Bruce', 'Hunton, Peter', 'Nagy, Éva']",,,,
,PMC,Influenza A/H1N1 from a pig perspective,,PMC2696714,,,,,"['Nava-Ocampo, Alejandro A.', 'Velázquez-Armenta, E. Yadira', 'Alonso-Spilsbury, María', 'Mota-Rojas, Daniel']",,,,
,PMC,Release of Rice dwarf virus from insect vector cells involves secretory exosomes derived from multivesicular bodies,,PMC2734036,,,"Plant reoviruses in insect vector cells are sequestered in spherical multivesicular compartments. We demonstrated previously that the plant-infecting reovirus Rice dwarf virus (RDV) exploits multivesicular compartments for the transport and release of viral particles from infected insect vector cells. These multivesicular compartments contain small vesicles and, morphologically, they resemble previously reported endosomal multivesicular bodies (MVBs) exploited by enveloped RNA viruses during budding from the plasma membrane of infected cells. Electron microscopy revealed that, at a late stage of infection, RDV virions are released, together with small vesicles similar to secreted vesicles (exosomes), from infected cells. The incorporation of lysosomes into the multivesicular compartments raised the possibility that functions of host MVBs are required for the efficient release of RDV virions from infected insect vector cells. An actin-myosin transport system has been shown to mediate the transport of these multivesicular compartments. In this addendum, we provide evidence for the proposed model of release of RDV virions from infected insect vector cells that exploits secretory exosomes derived from MVBs.",,"['Wei, Taiyun', 'Hibino, Hiroyuki', 'Omura, Toshihiro']",,,,
,PMC,Autoimmune disease triggered by infection with alphaproteobacteria,http://dx.doi.org/10.1586/ECI.09.23,PMC2742979,,,"Despite having long been postulated, compelling evidence for the theory that microbial triggers drive autoimmunity has only recently been reported. A specific association between Novosphingobium aromaticivorans, an ubiquitous alphaproteobacterium, and primary biliary cirrhosis (PBC) has been uncovered in patients with PBC. Notably, the association between Novosphingobium infection and PBC has been confirmed in a mouse model in which infection leads to the development of liver lesions resembling PBC concomitant with the production of anti-PDC-E2 antibodies that cross-react with conserved PDC-E2 epitopes shared by Novosphingobium. The discovery of infectious triggers of autoimmunity is likely to change our current concepts about the etiology of various autoimmune syndromes and may suggest new and simpler ways to diagnose and treat these debilitating diseases.",,"['Mohammed, Javid P', 'Mattner, Jochen']",,,,
,PMC,Synthesis and Pharmacological Evaluation of Schiff Bases of 4-(2-Aminophenyl)-Morpholines,http://dx.doi.org/10.4103/0250-474X.57292,PMC2865815,20502549,CC BY,"In the present study, a novel series of 4-(2-aminophenyl)morpholines were synthesized and characterized by IR, (1)H-NMR, (13)C NMR and mass spectral analysis. The synthesized compounds were screened for analgesic (100 and 200 mg/kg), antiinflammatory (200 and 400 mg/kg), antibacterial (Bacillus subtilis, Bacillus cereus, Staphylococcus epidermidis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli) and antifungal (Candida albicans and Aspergillus niger) activities. The minimum inhibitory concentrations of the compounds were also ascertained by agar streak dilution method. N-benzylidine-2-morpholoino benzenamine (1) and N-(3-nitro benzylidine)-2-morpholino benzenamine (3) exhibited significant analgesic, antiinflammatory and antimicrobial activities.",2009 Jul-Aug,"['Panneerselvam, P.', 'Priya, M. Gnanarupa', 'Kumar, N. Ramesh', 'Saravanan, G.']",Indian J Pharm Sci,,,
,PMC,Recent Trends in Emerging Infectious Diseases,,PMC3068824,,,,,,,,,
,PMC,Molar Malocclusions in Pine Voles (Microtus pinetorum),,PMC2715934,,,"Here we describe 5 cases of molar malocclusions in adult pine voles (Microtus pinetorum) used for behavioral endocrinology studies. This species belongs to the subfamily Microtinae, which possess aradicular hypsodont molars. The abnormal molars identified caused apparent difficulty in mastication, resulting in poor body condition necessitating euthanasia. Postmortem examination of the oral cavity revealed grossly elongated mandibular and maxillary molars with abnormal wear at occlusal surfaces. This colony health problem was addressed successfully by adding autoclaved hardwood sticks to each cage as an enrichment tool.",,"['Harvey, Stephen B', 'Alworth, Leanne C', 'Blas-Machado, Uriel']",,,,
,PMC,DUBs at a glance,http://dx.doi.org/10.1242/jcs.041046,PMC2704873,,,,,"Wilkinson, Keith D.",,,,
,PMC,Cost Analysis of Multiplex PCR Testing for Diagnosing Respiratory Virus Infections,http://dx.doi.org/10.1128/JCM.00556-09,PMC2738055,,,"We performed a cost analysis study using decision tree modeling to determine whether the use of multiplex PCR testing for respiratory viruses (xTAG RVP test) is a more or less costly strategy than the status quo testing methods used for the diagnosis of respiratory virus infections in pediatric patients. The decision tree model was constructed by using four testing strategies for respiratory virus detection, viz., direct fluorescent-antibody staining (DFA) alone, DFA plus shell vial culture (SVC), the xTAG RVP test alone, or DFA plus the xTAG RVP test. A review of the charts of 661 pediatric patients was used to determine the length of hospital stay, the number of days in isolation, antibiotic usage, and all other medical procedures performed. The cost of hospitalization by diagnostic status was determined on the basis of the average cost per patient and the number of patients in each arm of the decision tree. The cost per case was the highest for DFA plus SVC at $3,914 (in Canadian dollars), and the lowest was for the xTAG RVP test alone at $3,623, while the costs of DFA alone ($3,911) and DFA plus RVP ($3,849) were intermediate. When all four diagnostic strategies were compared, the least costly strategy was the xTAG RVP test alone when the prevalence of infection was 11% or higher and DFA alone when the prevalence was under 11%. These data indicate a savings of $291 per case investigated if the strategy of using the xTAG RVP test alone was used to replace the status quo test of DFA plus SVC, resulting in a savings of $529,620 per year in direct costs for the four Hamilton, Ontario, Canada, hospitals on the basis of the testing of specimens from 1,820 pediatric inpatients. We conclude that the use of the xTAG RVP test is the least costly strategy for the diagnosis of respiratory virus infections in children and would generate a significant savings for hospitals.",,"['Mahony, James B.', 'Blackhouse, Gord', 'Babwah, Jesse', 'Smieja, Marek', 'Buracond, Sonya', 'Chong, Sylvia', 'Ciccotelli, William', ""O'Shea, Tim"", 'Alnakhli, Daifallah', 'Griffiths-Turner, May', 'Goeree, Ron']",,,,
,PMC,Mitigation Approaches to Combat the Flu Pandemic,http://dx.doi.org/10.4103/0974-777X.56258,PMC2840954,20300402,CC BY,"Management of flu pandemic is a perpetual challenge for the medical fraternity since time immemorial. Animal to human transmission has been observed thrice in the last century within an average range of 11-39 years of antigenic recycling. The recent outbreak of influenza A (H1N1, also termed as swine flu), first reported in Mexico on April 26, 2009, occurred in the forty first year since last reported flu pandemic (July 1968). Within less than 50 days, it has assumed pandemic proportions (phase VI) affecting over 76 countries with 163 deaths/35,928 cases (as on 15(th) June 2009). It indicated the re-emergence of genetically reassorted virus having strains endemic to humans, swine and avian (H5N1). The World Health Organisation (WHO) member states have already pulled up their socks and geared up to combat such criticalities. Earlier outbreaks of avian flu (H5N1) in different countries led WHO to develop pandemic preparedness strategies with national/regional plans on pandemic preparedness. Numerous factors related to climatic conditions, socio-economic strata, governance and sharing of information/logistics at all levels have been considered critical indicators in monitoring the dynamics of escalation towards a pandemic situation. The National Disaster Management Authority (NDMA), Government of India, with the active cooperation of UN agencies and other stakeholders/experts has formulated a concept paper on role of nonhealth service providers during pandemics in April 2008 and released national guidelines - management of biological disasters in July 2008. These guidelines enumerate that the success of medical management endeavors like pharmaceutical (anti-viral Oseltamivir and Zanamivir therapies), nonpharmaceutical interventions and vaccination development etc., largely depends on level of resistance offered by mutagenic viral strain and rationale use of pharmaco therapeutic interventions. This article describes the mitigation approach to combat flu pandemic with its effective implementation at national, state and local levels.",2009 Jul-Dec,"['Chawla, Raman', 'Sharma, Rakesh Kumar', 'Madaan, Deepali', 'Dubey, Neha', 'Arora, Rajesh', 'Goel, Rajeev', 'Singh, Shefali', 'Kaushik, Vinod', 'Singh, Pankaj Kumar', 'Chabbra, Vivek', 'Bhardwaj, Janak Raj']",J Glob Infect Dis,,,
,PMC,Altered thymic selection and increased autoimmunity caused by ectopic expression of DRAK2 during T cell development,http://dx.doi.org/10.4049/jimmunol.0803530,PMC2724075,,,"Negative regulation of T cell receptor (TCR) signaling is an important mechanism enforcing immunological self-tolerance to prevent inappropriate activation of T cells and thus the development of autoimmune diseases. The lymphoid-restricted serine/threonine kinase DAP-related apoptotic kinase-2 (DRAK2) raises the TCR activation threshold by targeting TCR-induced calcium mobilization in thymocytes and peripheral T cells, and regulates positive thymic selection and peripheral T cell activation. Despite a hypersensitivity of peripheral drak2-deficient T cells, drak2-deficient mice are enigmatically resistant to induced autoimmunity in the model experimental autoimmune encephalomyelitis (EAE). In order to further evaluate the differential role of DRAK2 in central versus peripheral tolerance and to assess its impact on the development of autoimmune diseases, we have generated a transgenic (Tg) mouse strain ectopically expressing DRAK2 via the lck proximal promoter (1017-DRAK2 Tg mice). This transgene led to highest expression levels in double-positive thymocytes that are normally devoid of DRAK2. 1017-DRAK2 Tg mice displayed a reduction of single-positive CD4(+) and CD8(+) thymocytes in context with diminished negative selection in male HY TCR × 1017-DRAK2 Tg mice as well as peripheral T cell hypersensitivity, enhanced susceptibility to EAE and spontaneous autoimmunity. These findings suggest that alteration in thymocyte signaling thresholds impacts the sensitivity of peripheral T cell pools.",,"['Gatzka, Martina', 'Newton, Ryan H.', 'Walsh, Craig M.']",,,,
,PMC,The ideal reporting interval for an epidemic to objectively interpret the epidemiological time course,http://dx.doi.org/10.1098/rsif.2009.0153,PMC2842610,,,"The reporting interval of infectious diseases is often determined as a time unit in the calendar regardless of the epidemiological characteristics of the disease. No guidelines have been proposed to choose the reporting interval of infectious diseases. The present study aims at translating coarsely reported epidemic data into the reproduction number and clarifying the ideal reporting interval to offer detailed insights into the time course of an epidemic. We briefly revisit the dispersibility ratio, i.e. ratio of cases in successive reporting intervals, proposed by Clare Oswald Stallybrass, detecting technical flaws in the historical studies. We derive a corrected expression for this quantity and propose simple algorithms to estimate the effective reproduction number as a function of time, adjusting the reporting interval to the generation time of a disease and demonstrating a clear relationship among the generation-time distribution, reporting interval and growth rate of an epidemic. Our exercise suggests that an ideal reporting interval is the mean generation time, so that the ratio of cases in successive intervals can yield the reproduction number. When it is impractical to report observations every mean generation time, we also present an alternative method that enables us to obtain straightforward estimates of the reproduction number for any reporting interval that suits the practical purpose of infection control.",,"['Nishiura, Hiroshi', 'Chowell, Gerardo', 'Heesterbeek, Hans', 'Wallinga, Jacco']",,,,
,PMC,The Spike Protein of Murine Coronavirus Regulates Viral Genome Transport from the Cell Surface to the Endoplasmic Reticulum during Infection,http://dx.doi.org/10.1128/JVI.00956-09,PMC2753108,,,"We observed that the nonfusogenic mouse hepatitis virus (MHV) strain MHV-2 reached a titer of ∼2 log(10) higher than that of the fusogenic strain A59 in astrocytoma DBT cells. To determine whether the spike protein is responsible for the difference, a recombinant virus, Penn-98-1, that contains the A59 genome with a spike from MHV-2 was used to infect DBT cells. Results showed that Penn-98-1 behaved like MHV-2, thus establishing a role for the spike protein in viral growth. The inverse correlation between viral fusogenicity and growth was further established in four different cell types and with a fusogenic mutant, the S757R mutant, derived from isogenic Penn-98-1. While both A59 and Penn-98-1 entered cells at similar levels, viral RNA and protein syntheses were significantly delayed for A59. Interestingly, when the genomic RNAs were delivered directly into the cells via transfection, the levels of gene expression for these viruses were similar. Furthermore, cell fractionation experiments revealed that significantly more genomic RNAs for the nonfusogenic MHVs were detected in the endoplasmic reticulum (ER) within the first 2 h after infection than for the fusogenic MHVs. Pretreatment of Penn-98-1 with trypsin reversed its properties in syncytium formation, virus production, and genome transport to the ER. These findings identified a novel role for the spike protein in regulating the uncoating and delivery of the viral genome to the ER after internalization.",,"['Zhu, Hongqing', 'Yu, Dongdong', 'Zhang, Xuming']",,,,
,PMC,Protective and Pathologic Roles of the Immune Response to Mouse Hepatitis Virus Type 1: Implications for Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1128/JVI.00355-09,PMC2738266,,,"Intranasal mouse hepatitis virus type 1 (MHV-1) infection of mice induces lung pathology similar to that observed in severe acute respiratory syndrome (SARS) patients. However, the severity of MHV-1-induced pulmonary disease varies among mouse strains, and it has been suggested that differences in the host immune response might account for this variation. It has also been suggested that immunopathology may represent an important clinical feature of SARS. Little is known about the host immune response to MHV-1 and how it might contribute to some of the pathological changes detected in infected mice. In this study we show that an intact type I interferon system and the adaptive immune responses are required for controlling MHV-1 replication and preventing morbidity and mortality in resistant C57BL/6J mice after infection. The NK cell response also helps minimize the severity of illness following MHV-1 infection of C57BL/6J mice. In A/J and C3H/HeJ mice, which are highly susceptible to MHV-1-induced disease, we demonstrate that both CD4 and CD8 T cells contribute to morbidity during primary infection, and memory responses can enhance morbidity and mortality during subsequent reexposure to MHV-1. However, morbidity in A/J and C3H/HeJ mice can be minimized by treating them with immune serum prior to MHV-1 infection. Overall, our findings highlight the role of the host immune response in contributing to the pathogenesis of coronavirus-induced respiratory disease.",,"['Khanolkar, Aaruni', 'Hartwig, Stacey M.', 'Haag, Brayton A.', 'Meyerholz, David K.', 'Epping, Lecia L.', 'Haring, Jodie S.', 'Varga, Steven M.', 'Harty, John T.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.01039-09,PMC2704793,,,,,,,,,
,PMC,Tuberculous sarcoidosis: Is it a separate entity?,http://dx.doi.org/10.4103/0970-2113.53225,PMC2862507,20442837,CC BY,,2009 Jul-Sep,"['Agarwal, Ritesh', 'Gupta, Dheeraj']",Lung India,,,
,PMC,Psychoneuroimmunology Psychology's Gateway to the Biomedical Future,http://dx.doi.org/10.1111/j.1745-6924.2009.01139.x,PMC2742420,,,"How do stressful events and negative emotions influence the immune system, and how big are the effects? This broad question has been intensely interesting to psychoneuroimmunology researchers over the last three decades. Many promising lines of work underscore the reasons why this question is still so important and pivotal to understanding and other advances. New multidisciplinary permutations provide fresh vistas and emphasize the importance of training psychologists more broadly so that they will be central and essential players in the advancement of biomedical science.",,"Kiecolt-Glaser, Janice K.",,,,
,PMC,Facts and ideas from anywhere,,PMC2709099,,,,,"Roberts, William C.",,,,
,PMC,Prevention of Pulmonary Hypertension by Angiotensin Converting Enzyme 2 Gene Transfer,http://dx.doi.org/10.1161/HYPERTENSIONAHA.108.125468,PMC2732127,,,"In spite of recent advancements in the treatment of pulmonary hypertension (PH), successful control is yet to be accomplished. Abundant presence of ACE2 in the lungs, and its impressive effect in the prevention of acute lung injury, led us to test the hypothesis that pulmonary overexpression of this enzyme could produce beneficial outcomes against PH. Monocrotaline (MCT) treatment of mice for eight weeks resulted in significant increases in right ventricular systolic pressure (RVSP), right ventricle/left ventricle + septal (RV/LV+S) weight ratio and muscularization of pulmonary vessels. Administration of a lentiviral vector containing ACE2 (lenti-ACE2) seven days prior to MCT treatment prevented the increases in RVSP (Control: 25 ± 1 mmHg; MCT: 44 ± 5 mmHg; MCT+ACE2: 26 ± 1 mmHg, n=6, p<0.05) and RV/LV +S weight ratio (Control: 0.25 ± 0.01 mg/mg; MCT: 0.31 ± 0.01 mg/mg; MCT+ACE2: 0.26 ± 0.01mg/mg, n=8, p<0.05). A significant attenuation in muscularization of pulmonary vessels induced by MCT was also observed in animals overexpressing ACE2. These beneficial effects were associated with an increase in the AT(2) receptor/AT(1) receptor mRNA ratio. Also, PH-induced increases in pro-inflammatory cytokines were significantly attenuated by lenti-ACE2 treatment. Furthermore, ACE2 gene transfer in mice following six weeks of MCT treatment resulted in significant reversal of RVSP. These observations demonstrate that ACE2 overexpression prevents and reverses RVSP and associated pathophysiology in MCT-induced PH by a mechanism involving a shift from the vasoconstrictive, proliferative and fibrotic axis to the vasoprotective axis of the renin-angiotensin system and inhibition of pro-inflammatory cytokines.",,"['Yamazato, Yoriko', 'Ferreira, Anderson J', 'Hong, Kwon-Ho', 'Sriramula, Srinivas', 'Francis, Joseph', 'Yamazato, Masanobu', 'Yuan, Lihui', 'Bradford, Chastity N', 'Shenoy, Vinayak', 'Oh, Suk Paul', 'Katovich, Michael J', 'Raizada, Mohan K']",,,,
,PMC,"Vaccinia Virus Vaccines: Past, Present and Future",http://dx.doi.org/10.1016/j.antiviral.2009.06.006,PMC2742674,,,"Vaccinia virus (VACV) has been used more extensively for human immunization than any other vaccine. For almost two centuries, VACV was employed to provide cross-protection against variola virus, the causative agent of smallpox, until the disease was eradicated in the late 1970s. Since that time, continued research on VACV has produced a number of modified vaccines with improved safety profiles. Attenuation has been achieved through several strategies, including sequential passage in an alternative host, deletion of specific genes or genetic engineering of viral genes encoding immunomodulatory proteins. Some highly attenuated third- and fourth-generation VACV vaccines are now being considered for stockpiling against a possible re-introduction of smallpox through bioterrorism. Researchers have also taken advantage of the ability of the VACV genome to accommodate additional genetic material to produce novel vaccines against a wide variety of infectious agents, including a recombinant VACV encoding the rabies virus glycoprotein that is administered orally to wild animals. This review provides an in-depth examination of these successive generations of VACV vaccines, focusing on how the understanding of poxviral replication and viral gene function permits the deliberate modification of VACV immunogenicity and virulence.",,"['Jacobs, Bertram L.', 'Langland, Jeffrey O.', 'Kibler, Karen V.', 'Denzler, Karen L.', 'White, Stacy D.', 'Holechek, Susan A.', 'Wong, Shukmei', 'Huynh, Trung', 'Baskin, Carole R.']",,,,
,PMC,Treatment with a C5aR Antagonist Decreases Pathology and Enhances Behavioral Performance in Murine Models of Alzheimer’s Disease(),http://dx.doi.org/10.4049/jimmunol.0901005,PMC4067320,,,"Alzheimer’s disease (AD) is an age-related dementia, characterized by amyloid plaques, neurofibrillary tangles, neuroinflammation, and neuronal loss in the brain. Components of the complement system, known to produce a local inflammatory reaction, are associated with the plaques and tangles in AD brain, and thus a role for complement-mediated inflammation in the acceleration or progression of disease has been proposed. A complement activation product, C5a, is known to recruit and activate microglia and astrocytes in vitro by activation of a G protein-coupled cell-surface C5aR. Here, oral delivery of a cyclic hexapeptide C5a receptor antagonist (PMX205) for 2–3 mo resulted in substantial reduction of pathological markers such as fibrillar amyloid deposits (49 – 62%) and activated glia (42– 68%) in two mouse models of AD. The reduction in pathology was correlated with improvements in a passive avoidance behavioral task in Tg2576 mice. In 3xTg mice, PMX205 also significantly reduced hyperphosphorylated tau (69%). These data provide the first evidence that inhibition of a proinflammatory receptor-mediated function of the complement cascade (i.e., C5aR) can interfere with neuroinflammation and neurodegeneration in AD rodent models, suggesting a novel therapeutic target for reducing pathology and improving cognitive function in human AD patients.",,"['Fonseca, Maria I.', 'Ager, Rahasson R.', 'Chu, Shu-Hui', 'Yazan, Ozkan', 'Sanderson, Sam D.', 'LaFerla, Frank M.', 'Taylor, Stephen M.', 'Woodruff, Trent M.', 'Tenner, Andrea J.']",,,,
,PMC,"REPRODUCTIVE NUMBERS, EPIDEMIC SPREAD AND CONTROL IN A COMMUNITY OF HOUSEHOLDS",http://dx.doi.org/10.1016/j.mbs.2009.06.002,PMC2731010,,,"Many of the studies on emerging epidemics (such as SARS and pandemic flu) use mass action models to estimate reproductive numbers and the needed control measures. In reality, transmission patterns are more complex due to the presence of various social networks. One level of complexity can be accommodated by considering a community of households. Our study of transmission dynamics in a community of households emphasizes five types of reproductive numbers for the epidemic spread: household-to-household reproductive number, leaky vaccine-associated reproductive numbers, perfect vaccine reproductive number, growth rate reproductive number, and the individual reproductive number. Each of those carries different information about the transmission dynamics and the required control measures, and often some of those can be estimated from the data while others cannot. Simulations have shown that under certain scenarios there is an ordering for those reproductive numbers. We have proven a number of ordering inequalities under general assumptions about the individual infectiousness profiles. Those inequalities allow, for instance, to estimate the needed vaccine coverage and other control measures without knowing the various transmission parameters in the models. Along the way, we’ve also shown that in choosing between increasing vaccine efficacy and increasing coverage levels by the same factor, preference should go to efficacy.",,"['Goldstein, E.', 'Paur, K.', 'Fraser, C.', 'Kenah, E.', 'Wallinga, J.', 'Lipsitch, M.']",,,,
,PMC,Assay development and high throughput antiviral drug screening against Bluetongue virus,http://dx.doi.org/10.1016/j.antiviral.2009.06.004,PMC2727572,,,"Bluetongue virus (BTV) infection is one of the most important diseases of domestic livestock. There are no antivirals available against BTV disease. In this paper, we present the development, optimization and validation of an in vitro cell-based high-throughput screening (HTS) assay using the luminescent-based CellTiter-Glo reagent to identify novel antivirals against BTV. Conditions of the cytopathic effect (CPE)-based assay were optimized at cell density of 5 000 cells/well in medium containing 1% FBS and a multiplicity of infection at 0.01 in 384-well plate, with Z'-values ≥ 0.70, Coefficient of Variations ≥ 5.68 and signal-to-background ratio ≥ 7.10. This assay was further validated using a 9 532 compound library. The fully validated assay was then used to screen the 194 950 compound collection, which identified 693 compounds with > 30% CPE inhibition. The ten-concentration dose response assay identified 185 structures with IC(50) ≤ 100 μM, out of which 42 compounds were grouped into six analog series corresponding to six scaffolds enriched within the active set compared to their distribution in the library. The CPE-based assay development demonstrated its robustness and reliability, and its application in the HTS campaign will make significant contribution to the antiviral drug discovery against BTV disease.",,"['Li, Qianjun', 'Maddox, Clinton', 'Rasmussen, Lynn', 'Hobrath, Judith V.', 'White, Lucile E.']",,,,
,PMC,Palmitoylation of the Influenza A Virus M2 Protein Is Not Required for Virus Replication In Vitro but Contributes to Virus Virulence,http://dx.doi.org/10.1128/JVI.01129-09,PMC2738213,,,"The influenza A virus M2 protein has important roles during virus entry and in the assembly of infectious virus particles. The cytoplasmic tail of the protein can be palmitoylated at a cysteine residue, but this residue is not conserved in a number of human influenza A virus isolates. Recombinant viruses encoding M2 proteins with a serine substituted for the cysteine at position 50 were generated in the A/WSN/33 (H1N1) and A/Udorn/72 (H3N2) genetic backgrounds. The recombinant viruses were not attenuated for replication in MDCK cells, Calu-3 cells, or in primary differentiated murine trachea epithelial cell cultures, indicating there was no significant contribution of M2 palmitoylation to virus replication in vitro. The A/WSN/33 M2C50S virus displayed a slightly reduced virulence after infection of mice, suggesting that there may be novel functions for M2 palmitoylation during in vivo infection.",,"['Grantham, Michael L.', 'Wu, Wai-Hong', 'Lalime, Erin N.', 'Lorenzo, Maria E.', 'Klein, Sabra L.', 'Pekosz, Andrew']",,,,
,PMC,"Proteolytic Activation of the Spike Protein at a Novel RRRR/S Motif Is Implicated in Furin-Dependent Entry, Syncytium Formation, and Infectivity of Coronavirus Infectious Bronchitis Virus in Cultured Cells",http://dx.doi.org/10.1128/JVI.00613-09,PMC2738192,,,"The spike (S) protein of the coronavirus (CoV) infectious bronchitis virus (IBV) is cleaved into S1 and S2 subunits at the furin consensus motif RRFRR(537)/S in virus-infected cells. In this study, we observe that the S2 subunit of the IBV Beaudette strain is additionally cleaved at the second furin site (RRRR(690)/S) in cells expressing S constructs and in virus-infected cells. Detailed time course experiments showed that a peptide furin inhibitor, decanoyl-Arg-Val-Lys-Arg-chloromethylketone, blocked both viral entry and syncytium formation. Site-directed mutagenesis studies revealed that the S1/S2 cleavage by furin was not necessary for, but could promote, syncytium formation by and infectivity of IBV in Vero cells. In contrast, the second site is involved in the furin dependence of viral entry and syncytium formation. Mutations of the second site from furin-cleavable RRRR/S to non-furin-cleavable PRRRS and AAARS, respectively, abrogated the furin dependence of IBV entry. Instead, a yet-to-be-identified serine protease(s) was involved, as revealed by protease inhibitor studies. Furthermore, sequence analysis of CoV S proteins by multiple alignments showed conservation of an XXXR/S motif, cleavable by either furin or other trypsin-like proteases, at a position equivalent to the second IBV furin site. Taken together, these results suggest that proteolysis at a novel XXXR/S motif in the S2 subunit might be a common mechanism for the entry of CoV into cells.",,"['Yamada, Yoshiyuki', 'Liu, Ding Xiang']",,,,
,PMC,Toll-Like Receptor 4 Deficiency Increases Disease and Mortality after Mouse Hepatitis Virus Type 1 Infection of Susceptible C3H Mice,http://dx.doi.org/10.1128/JVI.01857-08,PMC2738158,,,"Severe acute respiratory syndrome (SARS) is characterized by substantial acute pulmonary inflammation with a high mortality rate. Despite the identification of SARS coronavirus (SARS-CoV) as the etiologic agent of SARS, a thorough understanding of the underlying disease pathogenesis has been hampered by the lack of a suitable animal model that recapitulates the human disease. Intranasal (i.n.) infection of A/J mice with the CoV mouse hepatitis virus strain 1 (MHV-1) induces an acute respiratory disease with a high lethality rate that shares several pathological similarities with SARS-CoV infection in humans. In this study, we examined virus replication and the character of pulmonary inflammation induced by MHV-1 infection in susceptible (A/J, C3H/HeJ, and BALB/c) and resistant (C57BL/6) strains of mice. Virus replication and distribution did not correlate with the relative susceptibilities of A/J, BALB/c, C3H/HeJ, and C57BL/6 mice. In order to further define the role of the host genetic background in influencing susceptibility to MHV-1-induced disease, we examined 14 different inbred mouse strains. BALB.B and BALB/c mice exhibited MHV-1-induced weight loss, whereas all other strains of H-2(b) and H-2(d) mice did not show any signs of disease following MHV-1 infection. H-2(k) mice demonstrated moderate susceptibility, with C3H/HeJ mice exhibiting the most severe disease. C3H/HeJ mice harbor a natural mutation in the gene that encodes Toll-like receptor 4 (TLR4) that disrupts TLR4 signaling. C3H/HeJ mice exhibit enhanced morbidity and mortality following i.n. MHV-1 infection compared to wild-type C3H/HeN mice. Our results indicate that TLR4 plays an important role in respiratory CoV pathogenesis.",,"['Khanolkar, Aaruni', 'Hartwig, Stacey M.', 'Haag, Brayton A.', 'Meyerholz, David K.', 'Harty, John T.', 'Varga, Steven M.']",,,,
,PMC,Whole-proteome phylogeny of large dsDNA virus families by an alignment-free method,http://dx.doi.org/10.1073/pnas.0905115106,PMC2722272,,,"The vast sequence divergence among different virus groups has presented a great challenge to alignment-based sequence comparison among different virus families. Using an alignment-free comparison method, we construct the whole-proteome phylogeny for a population of viruses from 11 viral families comprising 142 large dsDNA eukaryote viruses. The method is based on the feature frequency profiles (FFP), where the length of the feature (l-mer) is selected to be optimal for phylogenomic inference. We observe that (i) the FFP phylogeny segregates the population into clades, the membership of each has remarkable agreement with current classification by the International Committee on the Taxonomy of Viruses, with one exception that the mimivirus joins the phycodnavirus family; (ii) the FFP tree detects potential evolutionary relationships among some viral families; (iii) the relative position of the 3 herpesvirus subfamilies in the FFP tree differs from gene alignment-based analysis; (iv) the FFP tree suggests the taxonomic positions of certain “unclassified” viruses; and (v) the FFP method identifies candidates for horizontal gene transfer between virus families.",,"['Wu, Guohong Albert', 'Jun, Se-Ran', 'Sims, Gregory E.', 'Kim, Sung-Hou']",,,,
,PMC,T-cell immunosenescence: lessons learned from mouse models of aging,http://dx.doi.org/10.1016/j.it.2009.04.007,PMC3755270,,,"It is well established that increasing age is associated with a decreased capacity of the immune system to mediate effective immune responses to vaccination and invading pathogens. Because of the inherent limitations of conducting experiments in humans, much of what we have learned is owed to the utility of experimental mouse models of aging. Recent studies performed in the mouse have demonstrated mechanisms responsible for age-related declines in the function of CD4(+) and CD8(+) cells. This review describes key findings regarding age-related defects in T-cell function and discusses the impact these defects have on vaccine efficacy and immunity.",,"['Maue, Alexander C.', 'Yager, Eric J.', 'Swain, Susan L.', 'Woodland, David L.', 'Blackman, Marcia A.', 'Haynes, Laura']",,,,
,PMC,Mouse Adenovirus Type 1 Infection of Macrophages,http://dx.doi.org/10.1016/j.virol.2009.05.025,PMC2746394,,,"Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. MAV-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus. Here we determined the extent and functional importance of macrophage infection by MAV-1. Bone marrow-derived macrophages expressed MAV-1 mRNAs and proteins upon ex vivo infection. Adherent peritoneal macrophages from infected mice expressed viral mRNAs and produced infectious virus. Infected chemokine (C-C motif) receptor 2 (CCR2) knockout mice, which are defective for macrophage recruitment, did not show differences in survival or MAV-1 load compared to controls. In contrast, macrophage depletion using clodronate-loaded liposomes resulted in increased virus replication in spleens of a MAV-1-resistant mouse strain, BALB/cJ. Thus macrophages serve both as targets of infection and as effectors of the host response.",,"['Ashley, Shanna L.', 'Welton, Amanda R.', 'Harwood, Kirsten M.', 'Van Rooijen, Nico', 'Spindler, Katherine R.']",,,,
,PMC,Cancer Prevention Research–Then and Now,http://dx.doi.org/10.1038/nrc2646,PMC2838238,,,"Throughout history, human kind has won many battles against deadly diseases, including small pox, polio, tuberculosis and more recently severe acute respiratory syndrome. All of these diseases were defeated by prevention. Achieving cancer prevention is a global priority, but history tells us that the pathway to achievement is difficult and full of detours and roadblocks. Epidemiology and clinical evidence clearly indicate that specific factors are associated with an increased risk for cancer development. What can we learn from the past that is applicable to the reality of successful cancer prevention?",,"['Bode, Ann M.', 'Dong, Zigang']",,,,
,PMC,Fusion Peptide from Influenza Hemagglutinin Increases Membrane Surface Order: An Electron-Spin Resonance Study,http://dx.doi.org/10.1016/j.bpj.2009.04.015,PMC2712059,,,"A spin-labeling study of interactions of a fusion peptide from the hemagglutinin of the influenza virus, wt20, and a fusion-inactive mutant ΔG1 with dimyristoylphosphatidylcholine (DMPC) and 1-palmitoyl-2-oleoyl-phosphatdylcholine bilayers was performed. We found that upon binding of wt20, the ordering of headgroups and the ordering of acyl chains near the headgroup increased significantly, in a manner consistent with a cooperative phenomenon. However, changes in the order at the end of the acyl chains were negligible. The ordering effect of wt20 on the headgroup was much stronger at pH 5 than at pH 7. No effect of ΔG1 binding on the order of bilayers was evident. We also found that 1-palmitoyl-2-hydroxyl phosphatidylcholine, a membrane-fusion inhibitor, decreased the ordering of DMPC headgroups, whereas arachidonic acid, a membrane-fusion promoter, increased the ordering of DMPC headgroups. These results suggest that increases in headgroup ordering may be important for membrane fusion. We propose that upon binding of wt20, which is known to affect only the outer leaflet of the bilayer, this outer leaflet becomes more ordered, and thus more solid-like. Then the coupling between the hardened outer leaflet and the softer inner leaflet generates bending stresses in the bilayer, which tend to increase the negative curvature of the bilayer. We suggest that the increased ordering in the headgroup region enhances dipolar interactions and lowers electrostatic energy, which may provide an energy source for membrane fusion. Possible roles of bending stresses in promoting membrane fusion are discussed.",,"['Ge, Mingtao', 'Freed, Jack H.']",,,,
,PMC,Lesion size changes in osteonecrosis of the femoral head: a long-term prospective study using MRI,http://dx.doi.org/10.1007/s00264-009-0829-7,PMC2989007,,,"Osteonecrosis of the femoral head (ONFH) is one of the intractable diseases. It is controversial whether the lesion size assessed by magnetic resonance imaging (MRI) can change over time without any operative treatment. In this study, we used MRI to observe the lesion size changes of ONFH induced by corticosteroid administration in severe acute respiratory syndrome (SARS) patients. The study included 51 SARS patients (84 hips) with early-stage ONFH who did not receive any operative treatment and were diagnosed by MRI. All of the patients underwent MRI follow-ups. Each patient was evaluated on the basis of the lesion volume on MRI at every follow-up for further comparisons. At the first MRI scan, the mean lesion volume was 10.12 ± 8.05 cm(3) (range: 0.39–41.62 cm(3)). At the mid-term follow-up (2.5 years), the mean lesion volume was 7.82 ± 7.59 cm(3) (range: 0.11–39.65 cm(3)). At the final follow-up (five years), complete regression of the lesion was observed in six hips, and the mean lesion volume was 5.67 ± 6.58 cm(3) (range: 0.00–31.47 cm(3)). Overall, the lesion volume was reduced by >15% in 80 hips, and only four hips with relatively larger lesion volumes showed no apparent reductions. The reduction in lesion size of ONFH observed on MRI is a slow, discontinuous and time-dependent process.",,"['Zhao, Feng-chao', 'Li, Zi-rong', 'Zhang, Nian-fei', 'Wang, Bai-liang', 'Sun, Wei', 'Cheng, Li-ming', 'Liu, Zhao-hui']",,,,
,PMC,Comparison of DNA Vaccines Producing HIV-1 Gag and LAMP/gag Chimera In Rhesus Macaques Reveals Antigen-specific T Cell Responses With Distinct Phenotypes,http://dx.doi.org/10.1016/j.vaccine.2009.05.093,PMC2743166,,,"Optimized DNA expression vectors encoding the native HIV-1 Gag or a fusion of Gag with the lysosomal membrane associated protein 1 (LAMP) were compared for immunogenicity upon intramuscular DNA delivery in rhesus macaques. Both vaccines elicited CD4(+) T-cell responses, but with significant differences in the phenotype of the Gag-specific cells: the native Gag induced CD4(+) responses with a phenotype of central memory-like T cells (CD28(+) CD45RA(−)), whereas the LAMP/gag chimera induced CD4(+) responses with effector memory phenotype (CD28(−) CD45RA(−)). Antigen-specific T cells producing both IFN-γ and TNFα were found in the animals receiving the native Gag, whereas the LAMP/gag chimera induced humoral responses faster. These results demonstrate that modification of intracellular Gag trafficking results in the induction of distinct immune responses. Combinations of DNA vectors encoding both forms of antigen may be more potent in eliciting anti- HIV-1 immunity.",,"['Valentin, Antonio', 'Chikhlikar, Priya', 'Patel, Vainav', 'Rosati, Margherita', 'Maciel, Milton', 'Chang, Kern-Hee', 'Silvera, Peter', 'Felber, Barbara K.', 'Pavlakis, George N.', 'August, J. Thomas', 'Marques, Ernesto T. A.']",,,,
,PMC,Quantification of carnosine- related peptides by microchip electrophoresis with chemiluminescence detection,http://dx.doi.org/10.1016/j.ab.2009.06.012,PMC2744379,,,"A microchip electrophoresis (MCE) method with chemiluminescence (CL) detection was developed for the determination of carnosine-related peptides including carnosine, homocarnosine and anserine in biological samples. A simple integrated MCE-CL system was built to perform the assays. The highly sensitive CL detection was achieved by means of the CL reaction between hydrogen peroxide and N-(4-aminobutyl)- N-ethylisoluminol-tagged peptides in the presence of adenine as a CL enhancer and Co(2+) as a catalyst. Experimental conditions for analyte labeling, MCE separation, and CL detection were studied. MCE separation of the above said three peptides took less than 120 s. Detection limits (S/N=3) of 3.0×10(−8), 2.8×10(−8) and 3.4×10(−8) M were obtained for carnosine, anserine and homocarnosine, respectively. The present MCE-CL method was applied for the determination of carnosine, anserine and homocarnosine in human cerebrospinal fluid (CSF) and canine plasma. Homocarnosine was detected at the µM level in the CSF samples analyzed while the levels of carnosine and anserine in these samples were below the detection limit of the assay. Interestingly, both carnosine and anserine were detected in the canine plasma samples, but not homocarnosine.",,"['Zhao, Shulin', 'Huang, Yong', 'Shi, Ming', 'Huang, Junming', 'Liu, Yi-Ming']",,,,
,PMC,Viral calciomics: Interplays between Ca(2+) and virus,http://dx.doi.org/10.1016/j.ceca.2009.05.005,PMC3449087,,,"Ca(2+) is one of the most universal and versatile signaling molecules and is involved in almost every aspect of cellular processes. Viruses are adept at utilizing the universal Ca(2+) signal to create a tailored cellular environment that meets their own demands. This review summarizes most of the known mechanisms by which viruses perturb Ca(2+) homeostasis and utilize Ca(2+) and cellular Ca(2+)-binding proteins to their benefit in their replication cycles. Ca(2+) plays important roles in virion structure formation, virus entry, viral gene expression, posttranslational processing of viral proteins and virion maturation and release. As part of the review, we introduce an algorithm to identify linear “EF-hand” Ca(2+)-binding motifs which resulted in the prediction of a total of 93 previously unrecognized Ca(2+)-binding motifs in virus proteins. Many of these proteins are nonstructural proteins, a class of proteins among which Ca(2+) interactions had not been formerly appreciated. The presence of linear Ca(2+)-binding motifs in viral proteins enlarges the spectrum of Ca(2+)–virus interplay and expands the total scenario of viral calciomics.",,"['Zhou, Yubin', 'Frey, Teryl K.', 'Yang, Jenny J.']",,,,
,PMC,Risk Factors for Human Illness with Avian Influenza A (H5N1) Virus infection in China,http://dx.doi.org/10.1086/599206,PMC2759027,,,"BACKGROUND: In China, 30 human cases of H5N1 virus infection have been identified to date. We conducted a retrospective case-control study to identify risk factors for H5N1 disease in China. METHODS: A questionnaire about potential H5N1 exposures was administered to 28 H5N1 cases and 134 randomly selected age, gender, and location matched controls or proxies. Conditional logistic regression analyses were performed. RESULTS: Before their illness, urban cases had visited wet poultry markets while rural cases had exposure to sick or dead backyard poultry. Independent H5N1 risk factors in multivariable analyses were direct contact with sick or dead poultry (OR 506.6; 95% CI 15.7–16319.6; p=0.0004), indirect exposure to sick or dead poultry (OR 56.9; 95% CI 4.3–745.6; p=0.002), and visiting a wet poultry market (OR 15.4; 95% CI 3.0–80.2; p=0.001). CONCLUSIONS: To prevent human H5N1 cases in China, education to avoid direct or close exposures to sick or dead poultry should be increased, and interventions to prevent the spread of H5N1 at live poultry markets should be implemented.",,"['Zhou, Lei', 'Liao, Qiaohong', 'Dong, Libo', 'Huai, Yang', 'Bai, Tian', 'Xiang, Nijuan', 'Shu, Yuelong', 'Liu, Wei', 'Wang, Shiwen', 'Qin, Pengzhe', 'Wang, Min', 'Xing, Xuesen', 'Lv, Jun', 'Chen, Ray Y.', 'Feng, Zijian', 'Yang, Weizhong', 'Uyeki, Timothy M.', 'Yu, Hongjie']",,,,
,PMC,Characterization of SARS-CoV-specific memory T cells from recovered individuals 4 years after infection,http://dx.doi.org/10.1007/s00705-009-0409-6,PMC2796960,,,"SARS-CoV infection of human results in antigen-specific cellular and humoral immune responses. However, it is critical to determine whether SARS-CoV-specific memory T cells can persist for long periods of time. In this study, we analyzed the cellular immune response from 21 SARS-recovered individuals who had been diagnosed with SARS in 2003 by using ELISA, CBA, ELISpot and multiparameter flow cytometry assays. Our results demonstrated that low levels of specific memory T cell responses to SARS-CoV S, M, E and N peptides were detected in a proportion of SARS-recovered patients, and IFN-γ was the predominant cytokine produced by T cells after stimulation with peptides. Cytometry analysis indicated that the majority of memory CD8(+) T cells produced IFN-γ, whereas memory CD4(+) T cells produced IFN-γ, IL-2 or TNF-α. These results might provide valuable information on the cellular immune response in recovered SARS-CoV patients for the rational design of vaccines against SARS-CoV infection.",,"['Fan, Yan-Ying', 'Huang, Zi-Tong', 'Li, Li', 'Wu, Man-Hui', 'Yu, Tao', 'Koup, Richard A.', 'Bailer, Robert T.', 'Wu, Chang-You']",,,,
,PMC,Human Cytomegalovirus Suppresses Type I Interferon Secretion by Plasmacytoid Dendritic Cells through Its Interleukin 10 Homolog,http://dx.doi.org/10.1016/j.virol.2009.05.013,PMC2747589,,,"Type I interferons (IFNs) are innate cytokines with potent antiviral and immunoregulatory activities. It remains unclear how human cytomegalovirus (HCMV) can establish persistence in the face of these strongly antagonistic cytokines. In this study, we confirm that IFN-α efficiently suppresses the penetration of HCMV into susceptible cells, including monocytes, the major cell population in peripheral blood that is highly susceptible to HCMV infection. We further demonstrate that the HCMV-derived interleukin 10 (IL-10) homolog functions similar to cellular IL-10 and broadly inhibits TLR-induced transcriptional activation of IFN-α/β genes in plasmacytoid dendritic cells (PDCs), a major type I IFN-producer in vivo that is highly resistant to HCMV infection in vitro. These results suggest that HCMV subverts innate immunity by suppressing type I IFN production of PDCs during primary viral infection via its IL-10 homolog.",,"['Chang, W. L. William', 'Barry, Peter A.', 'Szubin, Richard', 'Wang, Dai', 'Baumgarth, Nicole']",,,,
,PMC,Promyelocytic Leukemia Zinc Finger Protein Regulates Interferon-Mediated Innate Immunity,http://dx.doi.org/10.1016/j.immuni.2009.04.013,PMC2711215,,,"Interferons (IFNs) direct innate and acquired immune responses and, accordingly, are used therapeutically to treat a number of diseases, yet the diverse effects they elicit are not fully understood. Here we identify the promyelocytic leukemia zinc finger (PLZF) protein as a previously unrecognized component of the IFN response. IFN stimulates an association between PLZF, the promyelocytic leukemia protein and histone deacetylase 1, to induce a decisive subset of IFN-stimulated genes (ISGs). Consequently, PLZF-deficient mice have a specific ISG defect and as a result are more susceptible to viral infection. This susceptibility correlates with a marked decrease in the expression of the key antiviral mediators and an impaired IFN-mediated induction of natural killer cell function. These results provide new insights into the regulatory mechanisms of IFN signaling and the induction of innate antiviral immunity.",,"['Xu, Dakang', 'Holko, Michelle', 'Sadler, Anthony J.', 'Scott, Bernadette', 'Higashiyama, Shigeki', 'Berkofsky-Fessler, Windy', 'McConnell, Melanie J.', 'Pandolfi, Pier Paolo', 'Licht, Jonathan D.', 'Williams, Bryan R.G.']",,,,
,PMC,"Spontaneous pathology of the common marmoset (Callithrix jacchus) and tamarins (Saguinus oedipus, Saguinus mystax)",http://dx.doi.org/10.1111/j.1600-0684.2009.00362.x,PMC2740810,,,"BACKGROUND: Marmosets and tamarins are increasingly used in research, but their pathology remains poorly defined compared to old world primates. METHODS: Necropsy records of 129 marmosets and 52 tamarins were reviewed; none were used experimentally. RESULTS: The most common marmoset lesions were dehydration, emaciation, nephritis, colitis and inanition. The most common tamarin lesions were dehydration, ascites, emaciation and congestive heart failure. Colitis and heart disease were the most common cause of death in marmosets and tamarins, respectively. Immature marmoset and tamarin deaths often occurred within the first month of life. Immature marmosets usually died from inanition, stillbirth and colitis; immature tamarins from atelectasis, stillbirth, heart failure and colitis. Lymphoma was the most common neoplasm for both marmosets and tamarins. CONCLUSION: The findings were similar to prior reports with differences in frequency and severity. We report the first case of endometriosis in a marmoset.",,"['David, John M.', 'Dick, Edward J.', 'Hubbard, Gene B.']",,,,
,PMC,Characterization of Rabbit CD5 Isoforms,http://dx.doi.org/10.1016/j.molimm.2009.05.026,PMC2757743,,,"Previously described polyclonal or monoclonal antibodies (mAb) to rabbit CD5, raised against expressed recombinant protein or peptides, recognize CD5 on most rabbit B cells. The mAb KEN-5 was originally reported to recognize rabbit CD5. However, KEN-5 binds almost exclusively to T cells and only to a minor population of B cells. We show here that by Enzyme-linked Immunosorbent Assay (ELISA), KEN-5 binds to recombinant rabbit CD5. This interaction is partially inhibited by polyclonal goat anti-CD5 antibody. In addition, immunoprecipitations from lysates of surface biotinylated rabbit lymphocytes with KEN-5 or our anti-CD5 mAb isolate molecules that migrate identically on gels with the same approximate relative molecular mass of 67,000 M(r). By flow cytometric analyses of individual cells from spleen, thymus and appendix, KEN-5 recognizes CD5-like molecules mainly on T cells and on 3-6% of IgM(+) B cells. Immunohistochemical staining of splenic and appendix tissues and confocal immunofluorescent imaging confirm and extend results from flow cytometric analyses. Quantitation of fluorescent colocalization indicates that staining by KEN-5 colocalizes with staining by anti-CD5 on small percentages lymphocytes in splenic tissue sections. As CD5 has both N- and O-linked glycosylation, we hypothesised that differential binding of KEN-5 to T cells and B-cells may be explained by different glycan structures on the CD5 present on T compared to B cells. This hypothesis is supported by ELISA data that show that deglycosylation diminishes the binding of KEN-5 to recombinant rabbit CD5. Screening KEN-5 on an array with 406 glycans was inconclusive. Although we did not identify a strongly binding glycan structure, the data are suggestive that the epitope recognized by KEN-5 may be influenced by glycan structures. The epitope this mAb recognizes may either be the glycan itself, or more likely, is influenced by neighboring glycan structure. Our findings suggest that development, selection and function of different B- and T-cell subsets or their preferential survival may be directly or indirectly dependent on different glycan structures associated with CD5 or CD5-like molecules expressed on T cells compared to B cells.",,"['Pospisil, Richard', 'Kabat, Juraj', 'Mage, Rose G.']",,,,
,PMC,For the record,http://dx.doi.org/10.1503/cmaj.090869,PMC2691431,,,,,,,,,
,PMC,"Canada’s ability to respond to a national health crisis hampered by jurisdictional issues, untested emergency plans",http://dx.doi.org/10.1503/cmaj.090870,PMC2691430,,,,,"Silversides, Ann",,,,
,PMC,RNA Interference-Mediated Silencing of the Respiratory Syncytial Virus Nucleocapsid Defines a Potent Antiviral Strategy,http://dx.doi.org/10.1128/AAC.00014-09,PMC2737834,,,"We describe the design and characterization of a potent human respiratory syncytial virus (RSV) nucleocapsid gene-specific small interfering RNA (siRNA), ALN-RSV01. In in vitro RSV plaque assays, ALN-RSV01 showed a 50% inhibitory concentration of 0.7 nM. Sequence analysis of primary isolates of RSV showed that the siRNA target site was absolutely conserved in 89/95 isolates, and ALN-RSV01 demonstrated activity against all isolates, including those with single-mismatch mutations. In vivo, intranasal dosing of ALN-RSV01 in a BALB/c mouse model resulted in potent antiviral efficacy, with 2.5- to 3.0-log-unit reductions in RSV lung concentrations being achieved when ALN-RSV01 was administered prophylactically or therapeutically in both single-dose and multidose regimens. The specificity of ALN-RSV01 was demonstrated in vivo by using mismatch controls; and the absence of an immune stimulatory mechanism was demonstrated by showing that nonspecific siRNAs that induce alpha interferon and tumor necrosis factor alpha lack antiviral efficacy, while a chemically modified form of ALN-RSV01 lacking measurable immunostimulatory capacity retained full activity in vivo. Furthermore, an RNA interference mechanism of action was demonstrated by the capture of the site-specific cleavage product of the RSV mRNA via rapid amplification of cDNA ends both in vitro and in vivo. These studies lay a solid foundation for the further investigation of ALN-RSV01 as a novel therapeutic antiviral agent for clinical use by humans.",,"['Alvarez, Rene', 'Elbashir, Sayda', 'Borland, Todd', 'Toudjarska, Ivanka', 'Hadwiger, Philipp', 'John, Mathias', 'Roehl, Ingo', 'Morskaya, Svetlana Shulga', 'Martinello, Rick', 'Kahn, Jeffrey', 'Van Ranst, Mark', 'Tripp, Ralph A.', 'DeVincenzo, John P.', 'Pandey, Rajendra', 'Maier, Martin', 'Nechev, Lubomir', 'Manoharan, Muthiah', 'Kotelianski, Victor', 'Meyers, Rachel']",,,,
,PMC,Antiviral Activity of Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice,http://dx.doi.org/10.1128/AAC.01509-08,PMC2715625,,,"Until recently, human coronaviruses (HCoVs), such as HCoV strain OC43 (HCoV-OC43), were mainly known to cause 15 to 30% of mild upper respiratory tract infections. In recent years, the identification of new HCoVs, including severe acute respiratory syndrome coronavirus, revealed that HCoVs can be highly pathogenic and can cause more severe upper and lower respiratory tract infections, including bronchiolitis and pneumonia. To date, no specific antiviral drugs to prevent or treat HCoV infections are available. We demonstrate that chloroquine, a widely used drug with well-known antimalarial effects, inhibits HCoV-OC43 replication in HRT-18 cells, with a 50% effective concentration (± standard deviation) of 0.306 ± 0.0091 μM and a 50% cytotoxic concentration (± standard deviation) of 419 ± 192.5 μM, resulting in a selectivity index of 1,369. Further, we investigated whether chloroquine could prevent HCoV-OC43-induced death in newborn mice. Our results show that a lethal HCoV-OC43 infection in newborn C57BL/6 mice can be treated with chloroquine acquired transplacentally or via maternal milk. The highest survival rate (98.6%) of the pups was found when mother mice were treated daily with a concentration of 15 mg of chloroquine per kg of body weight. Survival rates declined in a dose-dependent manner, with 88% survival when treated with 5 mg/kg chloroquine and 13% survival when treated with 1 mg/kg chloroquine. Our results show that chloroquine can be highly effective against HCoV-OC43 infection in newborn mice and may be considered as a future drug against HCoVs.",,"['Keyaerts, Els', 'Li, Sandra', 'Vijgen, Leen', 'Rysman, Evelien', 'Verbeeck, Jannick', 'Van Ranst, Marc', 'Maes, Piet']",,,,
,PMC,Progress on the Development of Therapeutics against West Nile Virus,http://dx.doi.org/10.1016/j.antiviral.2009.05.006,PMC2759769,,,"A decade has passed since the appearance of West Nile virus (WNV) in humans in the Western Hemisphere in New York City. During this interval, WNV spread inexorably throughout North and South America and caused millions of infections ranging from a sub-clinical illness, to a self-limiting febrile syndrome or lethal neuroinvasive disease. Its entry into the United States triggered intensive research into the basic biology of WNV and the elements that comprise a protective host immune response. Although no therapy is currently approved for use in humans, several strategies are being pursued to develop effective prophylaxis and treatments. This review describes the current state of knowledge on epidemiology, clinical presentation, pathogenesis, and immunobiology of WNV infection, and highlights progress toward an effective therapy.",,"Diamond, Michael S",,,,
,PMC,"RNA CONFORMATIONAL CHANGES IN THE LIFE CYCLES OF RNA VIRUSES, VIROIDS, AND VIRUS-ASSOCIATED RNAS",http://dx.doi.org/10.1016/j.bbagrm.2009.05.005,PMC2784224,,,"The rugged nature of the RNA structural free energy landscape allows cellular RNAs to respond to environmental conditions or fluctuating levels of effector molecules by undergoing dynamic conformational changes that switch on or off activities such as catalysis, transcription or translation. Infectious RNAs must also temporally control incompatible activities and rapidly complete their life cycle before being targeted by cellular defenses. Viral genomic RNAs must switch between translation and replication, and untranslated subviral RNAs must control other activities such as RNA editing or self-cleavage. Unlike well-characterized riboswitches in cellular RNAs, the control of infectious RNA activities by altering the configuration of functional RNA domains has only recently been recognized. In this review, we will present some of these molecular rearrangements found in RNA viruses, viroids and virus-associated RNAs, relating how these dynamic regions were discovered, the activities that might be regulated, and what factors or conditions might cause a switch between conformations.",,"['Simon, Anne E.', 'Gehrke, Lee']",,,,
,PMC,Effects of aging on T cell function,http://dx.doi.org/10.1016/j.coi.2009.05.009,PMC3800142,,,"Immunosenescence influences many components of the immune system. Most importantly, profound changes in T cell function are evident in older individuals. The impact of aging on specific T cell subsets has been difficult to examine, but recent advances in murine model systems and new insights into T cell function have allowed for the more precise examination of how T cell responses change with aging. Importantly, recent studies have shown that age-related enhancement of both Th17 generation and regulatory T cell function may contribute to significant changes in immune function. In this review, we summarize the current views on how aging influences the factors that impact T cell function and how this can affect the immune response to infections, vaccinations, and tumors.",,"['Haynes, Laura', 'Maue, Alexander C']",,,,
,PMC,Multiplex PCR tests sentinel the appearance of pandemic influenza viruses including H1N1 swine influenza,http://dx.doi.org/10.1016/j.jcv.2009.05.031,PMC5153328,,,"BACKGROUND: Since the turn of the century seven new respiratory viruses have infected man and two of these have resulted in worldwide epidemics. Both SARS Coronavirus which quickly spread to 29 countries in February 2003 and H1N1 swine influenza that recently spread from Mexico to 30 countries in three weeks represent major pandemic threats for mankind. Diagnostic assays are required to detect novel influenza strains with pandemic potential. OBJECTIVE: In this report we evaluate the ability of a multiplex PCR test (xTAG(™)RVP) to detect new, “non-seasonal” influenza viruses including the H1N1 swine influenza A/swine/California/04/2009. STUDY DESIGN: Laboratory based study using retrospective and prospective specimens. RESULTS: This multiplex PCR test detected the present of non-seasonal (non-H1, non-H3) influenza in 20 of 20 patients infected with H1N1 swine flu virus. In addition to detecting the current swine flu the xTAG(™) RVP test detected the H5N1 A/Vietnam/1203/2004 high pathogenicity avian influenza virus that circulated in South East Asia in 2003 as well as 17 out of 17 influenza A viruses representing 11 HA subtypes isolated from birds, swine and horses not yet seen in the human population. CONCLUSION: Based on these results we believe that this molecular test can perform an important role as a sentinel test to detect novel non-seasonal influenza A viruses in patients presenting with influenza-like illness (ILI) and therefore act as an early warning system for the detection of future pandemic influenza threats.",,"['Mahony, James B.', 'Hatchette, Todd', 'Ojkic, Davor', 'Drews, Steven J.', 'Gubbay, Jonathan', 'Low, Donald E.', 'Petric, Martin', 'Tang, Patrick', 'Chong, Sylvia', 'Luinstra, Kathy', 'Petrich, Astrid', 'Smieja, Marek']",,,,
,PMC,A map and new directions for the (pro)renin receptor in the brain: focus on “A role of the (pro)renin receptor in neuronal cell differentiation”,http://dx.doi.org/10.1152/ajpregu.00287.2009,PMC2724233,,,,,"Lazartigues, Eric",,,,
,PMC,Solution Characterization of the Extracellular Region of CD147 and Its Interaction with Its Enzyme Ligand Cyclophilin A,http://dx.doi.org/10.1016/j.jmb.2009.05.080,PMC2940942,,,"The CD147 receptor plays an integral role in numerous diseases by stimulating the expression of several protein families and serving as the receptor for extracellular cyclophilins; however, neither CD147 nor its interactions with its cyclophilin ligands have been well characterized in solution. CD147 is a unique protein in that it can function both at the cell membrane and after being released from cells where it continues to retain activity. Thus, the CD147 receptor functions through at least two mechanisms that include both cyclophilin-independent and cyclophilin-dependent modes of action. In regard to CD147 cyclophilin-independent activity, CD147 homophilic interactions are thought to underlie its activity. In regard to CD147 cyclophilin-dependent activity, cyclophilin/CD147 interactions may represent a novel means of signaling since cyclophilins are also peptidyl–prolyl isomerases. However, direct evidence of catalysis has not been shown within the cyclophilin/CD147 complex. In this report, we have characterized the solution behavior of the two most prevalent CD147 extracellular isoforms through biochemical methods that include gel-filtration and native gel analysis as well as directly through multiple NMR methods. All methods indicate that the extracellular immunoglobulin-like domains are monomeric in solution and, thus, suggest that CD147 homophilic interactions in vivo are mediated through other partners. Additionally, using multiple NMR techniques, we have identified and characterized the cyclophilin target site on CD147 and have shown for the first time that CD147 is also a substrate of its primary cyclophilin enzyme ligand, cyclophilin A.",,"['Schlegel, Jennifer', 'Redzic, Jasmina S.', 'Porter, Christopher C.', 'Yurchenko, Vyacheslav', 'Bukrinsky, Michael', 'Labeikovsky, Wladimir', 'Armstrong, Geoffrey S.', 'Zhang, Fengli', 'Isern, Nancy G.', 'DeGregori, James', 'Hodges, Robert', 'Eisenmesser, Elan Zohar']",,,,
,PMC,Coronavirus Immunoreactivity in Individuals With a Recent Onset of Psychotic Symptoms,http://dx.doi.org/10.1093/schbul/sbp052,PMC3004184,,,"Prenatal influenza exposure increases the risk for schizophrenia and brings to question how other respiratory viruses may contribute to neuropsychiatric disease etiopathology. Human coronaviruses cause respiratory infections that range in seriousness from common colds to severe acute respiratory syndrome. Like influenza, coronaviruses can be neurotropic. To test for associations between coronaviruses and serious mental disorders, we utilized a recently developed assay and measured immunoglobulin G (IgG) response against 4 human coronavirus strains (229E, HKU1, NL63, and OC43) in 106 patients with a recent onset of psychotic symptoms and 196 nonpsychiatric controls. We expressed results quantitatively as antibody levels and qualitatively as seroprevalence relative to a defined seropositivity cutoff value. Patient IgG levels were higher than controls for HKU1, NL63, and OC43, with HKU1 and NL63 both showing highly significant patient-to-control differences (HKU1, P ≤ .002; NL63, P ≤ .00001). All 4 coronaviruses were more seroprevalent in patients vs controls, with greatest intergroup differences observed for HKU1 (93% vs 77%, P ≤ .0001). HKU1 and NL63 associations with the patient group were further supported by multivariate analyses that controlled for age, gender, race, socioeconomic status, and smoking status (HKU1, odds ratio [OR] = 1.32, 95% confidence interval [CI] = 1.03–1.67, P ≤ .027; NL63, OR = 2.42, 95% CI = 1.25–4.66, P ≤ .008). Among patients, NL63 was associated with schizophrenia-spectrum (OR = 3.10, 95% CI = 1.27–7.58, P ≤ .013) but not mood disorders. HKU1 and NL63 coronavirus exposures may represent comorbid risk factors in neuropsychiatric disease. Future studies should explore links between the timing of coronavirus infections and subsequent development of schizophrenia and other disorders with psychotic symptoms.",,"['Severance, Emily G.', 'Dickerson, Faith B.', 'Viscidi, Raphael P.', 'Bossis, Ioannis', 'Stallings, Cassie R.', 'Origoni, Andrea E.', 'Sullens, Anne', 'Yolken, Robert H.']",,,,
,PMC,Infection on a chip: a microscale platform for simple and sensitive cell-based virus assays,http://dx.doi.org/10.1007/s10544-008-9263-7,PMC2869488,,,"The plaque assay has long served as the “gold standard” to measure virus infectivity and test antiviral drugs, but the assay is labor-intensive, lacks sensitivity, uses excessive reagents, and is hard to automate. Recent modification of the assay to exploit flow-enhanced virus spread with quantitative imaging has increased its sensitivity. Here we performed flow-enhanced infection assays in microscale channels, employing passive fluid pumping to inoculate cell monolayers with virus and drive infection spread. Our test of an antiviral drug (5-fluorouracil) against vesicular stomatitis virus infections of BHK cell monolayers yielded a two-fold improvement in sensitivity, relative to the standard assay based on plaque counting. The reduction in scale, simplified fluid handling, image-based quantification, and higher assay sensitivity will enable infection measurements for high-throughput drug screening, sero-conversion testing, and patient-specific diagnosis of viral infections.",,"['Zhu, Ying', 'Warrick, Jay W.', 'Haubert, Kathryn', 'Beebe, David J.', 'Yin, John']",,,,
,PMC,Swine flu of 1976: lessons from the past. An interview with Dr Harvey Fineberg.,http://dx.doi.org/10.2471/BLT.09.040609,PMC2686218,,,"In 1976, a late winter outbreak of swine flu at a military base in the USA led to fears of a devastating pandemic. President Gerald Ford announced a plan to vaccinate everyone in the country. By the end of the year, 40 million out of some 200 million Americans were vaccinated for the new strain, but no pandemic appeared and public health credibility suffered. Dr Harvey Fineberg tells the Bulletin why his 1978 study of that public health response is still relevant today.",,,,,,
,PMC,Apocalypse or redemption: responding to extensively drug-resistant tuberculosis,http://dx.doi.org/10.2471/BLT.08.051698,PMC2686205,,,,,"['Upshur, Ross', 'Singh, Jerome', 'Ford, Nathan']",,,,
,PMC,"The sounds of silence: Public goods, externalities, and the value of infectious disease control programs",,PMC2706405,,,,,"['Fisman, David N', 'Laupland, Kevin B']",,,,
,PMC,One world – one health,http://dx.doi.org/10.7861/clinmedicine.9-3-259,PMC4953616,,,,,"['Karesh, William B', 'Cook, Robert A']",,,,
,PMC,Advances in infectious diseases,http://dx.doi.org/10.7861/clinmedicine.9-3-254,PMC4953613,,,,,"Ellis, Chris",,,,
,PMC,"Global health: current issues, future trends and foreign policy",http://dx.doi.org/10.7861/clinmedicine.9-3-247,PMC4953612,,,,,"Kirwan, Daniela",,,,
,PMC,Endpoints for Mouse Abdominal Tumor Models: Refinement of Current Criteria,,PMC2733284,,,"Accurate, rapid, and noninvasive health assessments are required to establish more appropriate endpoints in mouse cancer models where tumor size is not easily measured. We evaluated potential endpoints in mice with experimentally induced peritoneal lymphoma, an abdominal tumor model, by comparing body weight, body condition, and behavior with those of a control group of mice not developing lymphoma. Our hypothesis was that body weight would increase or plateau, whereas body condition and behavioral scores would decrease, as disease progressed. Results indicated that body weight did not differ significantly between the control and experimental groups, but the experimental group experienced significant decreases in both body condition and behavioral scores. Our results support the use of body condition and behavioral scoring as adjunctive assessment methods for mice involved in abdominal lymphoma tumor studies in which health may decline despite an increase or plateau in body weight.",,"['Paster, Eden V', 'Villines, Kimberly A', 'Hickman, Debra L']",,,,
,PMC,Happy New Fear: New Disease of the Year,http://dx.doi.org/10.3325/cmj.2009.50.332,PMC2702748,,,,,"Lončarek, Karmen",,,,
,PMC,Strategies to overcome host immunity to adenovirus vectors in vaccine development,http://dx.doi.org/10.1586/erv.09.29,PMC3700409,,,"The first clinical evaluations of adenovirus (Ad)-based vectors for gene therapy were initiated in the mid-1990s and led to great anticipation for future utility. However, excitement surrounding gene therapy, particularly Ad-based therapy, was diminished upon the death of Jesse Gelsinger, and recent discouraging results from the HIV vaccine STEP trial have brought efficacy and safety issues to the forefront again. Even so, Ad vectors are still considered among the safest and most effective vaccine vectors. Innate and pre-existing immunity to Ad mediate much of the acute toxicities and reduced therapeutic efficacies observed following vaccination with this vector. Thus, innovative strategies must continue to be developed to reduce Ad-specific antigenicity and immune recognition. This review provides an overview and critique of the most promising strategies, including results from preclinical trials in mice and nonhuman primates, which aim to revive the future of Ad-based vaccines.",,"['Thacker, Erin E', 'Timares, Laura', 'Matthews, Qiana L']",,,,
,PMC,Immunosuppressive human anti-lymphocyte autoantibodies specific for the type 1 sphingosine 1-phosphate receptor,http://dx.doi.org/10.1096/fj.08-124891,PMC2698662,,,"Anti-lymphocyte antibodies (Abs) that suppress T-cell chemotactic and other responses to sphingosine 1-phosphate (S1P), but not to chemokines, were found in a lymphopenic patient with recurrent infections. Lymphocyte type 1 S1P receptor (S1P(1)) that transduces S1P chemotactic stimulation was recognized by patient Abs in Western blots of T cells, S1P(1) transfectants, and S1P(1)-hemagglutinin purified by monoclonal anti-hemagglutinin Ab absorption. The amino terminus of S1P(1), but not any extracellular loop, prevented anti-S1P(1) Ab suppression of S1P(1) signaling and T-cell chemotaxis to S1P. Human purified anti-S1P(1) Abs decreased mouse blood lymphocyte levels by a mean of 72%, suppressed mouse T-cell chemotaxis to S1P in vivo, and significantly reduced the severity of dextran sodium sulfate-induced colitis in mice. Human Abs to the amino terminus of S1P(1) suppress T-cell trafficking sufficiently to impair host defense and provide therapeutic immunosuppression.—Liao, J.-J., Huang, M.-C., Fast, K., Gundling, K., Yadav, M., Van Brocklyn, J. R., Wabl, M. R., Goetzl, E. J. Immunosuppressive human anti-lymphocyte autoantibodies specific for the type 1 sphingosine 1-phosphate receptor.",,"['Liao, Jia-Jun', 'Huang, Mei-Chuan', 'Fast, Katharine', 'Gundling, Katherine', 'Yadav, Mahesh', 'Van Brocklyn, James R.', 'Wabl, Matthias R.', 'Goetzl, Edward J.']",,,,
,PMC,Mannan-binding lectin deficiency modulates the humoral immune response dependent on the genetic environment,http://dx.doi.org/10.1111/j.1365-2567.2008.03016.x,PMC2691793,,,"Mannan-binding lectin (MBL) is a plasma protein implicated in innate immune defence against a broad range of microorganisms, including viruses. It is also thought that MBL plays a role in the recruitment of the specific clonal immune response. This was studied by injecting soluble hepatitis B surface antigen (HBsAg) intravenously into mice deficient in both MBL-A and MBL-C (MBL DKO mice). The MBL DKO animals on mixed genetic background (SV129EvSv × C57BL/6) produced higher antibody titres than the wild-type littermates. After primary challenge with the antigen the immunoglobulin M anti-HBsAg antibody titres were threefold higher in the MBL DKO mice than in the wild-type mice. Following the boost, the immunoglobulin G anti-HBsAg antibody titres were 10-fold higher in the MBL DKO mice, suggesting that MBL plays a role in a negative feedback regulation of adaptive immunity. However, the modulating effect of MBL was dependent on the genetic environment. The MBL DKO mice backcrossed on a C57BL/6 background showed the opposite response with the MBL DKO mice now producing fewer antibodies than the wild-type animals, whereas MBL deficiency in mice with the SV129EvSv background did not show any effect in antibody production. These findings indicate that the modifying effect of MBL on the humoral immune response is influenced by the genetic environment.",,"['Ruseva, Marieta', 'Kolev, Martin', 'Dagnaes-Hansen, Frederik', 'Hansen, Soren B', 'Takahashi, Kazue', 'Ezekowitz, Alan', 'Thiel, Steffen', 'Jensenius, Jens C', 'Gadjeva, Mihaela']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00719-09,PMC2681976,,,,,,,,,
,PMC,Non-viral Methods for siRNA Delivery,http://dx.doi.org/10.1021/mp800134q,PMC2692493,,,"RNA interference (RNAi) as a mechanism to selectively degrade messenger RNA (mRNA) expression has emerged as a potential novel approach for drug target validation and the study of functional genomics. Small interfering RNAs (siRNA) therapeutics has developed rapidly and already there are clinical trials ongoing or planned. Although other challenges remain, delivery strategies for siRNA become the main hurdle that must be resolved prior to the full-scale clinical development of siRNA therapeutics. This article provides an overview of the current delivery strategies for synthetic siRNA, focusing on the targeted, self-assembled nanoparticles which show potential to become a useful and efficient tool in cancer therapy.",,"['Gao, Kun', 'Huang, Leaf']",,,,
,PMC,Coronaviruses post-SARS: Update on replication and pathogenesis,http://dx.doi.org/10.1038/nrmicro2147,PMC2830095,,,"While coronaviruses were first identified nearly 60 years ago, they received notoriety in 2003 when one of their members was identified as the etiological agent of the Severe Acute Respiratory Syndrome (SARS-CoV) 1. Previously these viruses were known to be important agents of respiratory and enteric infections of domestic and companion animals and to cause approximately 15% of all cases of the common cold. This Review focuses on recent advances in our understanding of the mechanisms of coronavirus replication, interactions with the host immune response and disease pathogenesis and highlights the recent identification of numerous novel coronaviruses and the propensity of this virus family to cross species barriers.",,"['Perlman, Stanley', 'Netland, Jason']",,,,
,PMC,International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the Formyl Peptide Receptor (FPR) Family,http://dx.doi.org/10.1124/pr.109.001578,PMC2745437,,,"Formyl peptide receptors (FPRs) are a small group of seven-transmembrane domain, G protein-coupled receptors that are expressed mainly by mammalian phagocytic leukocytes and are known to be important in host defense and inflammation. The three human FPRs (FPR1, FPR2/ALX, and FPR3) share significant sequence homology and are encoded by clustered genes. Collectively, these receptors bind an extraordinarily numerous and structurally diverse group of agonistic ligands, including N-formyl and nonformyl peptides of different composition, that chemoattract and activate phagocytes. N-formyl peptides, which are encoded in nature only by bacterial and mitochondrial genes and result from obligatory initiation of bacterial and mitochondrial protein synthesis with N-formylmethionine, is the only ligand class common to all three human receptors. Surprisingly, the endogenous anti-inflammatory peptide annexin 1 and its N-terminal fragments also bind human FPR1 and FPR2/ALX, and the anti-inflammatory eicosanoid lipoxin A4 is an agonist at FPR2/ALX. In comparison, fewer agonists have been identified for FPR3, the third member in this receptor family. Structural and functional studies of the FPRs have produced important information for understanding the general pharmacological principles governing all leukocyte chemoattractant receptors. This article aims to provide an overview of the discovery and pharmacological characterization of FPRs, to introduce an International Union of Basic and Clinical Pharmacology (IUPHAR)-recommended nomenclature, and to discuss unmet challenges, including the mechanisms used by these receptors to bind diverse ligands and mediate different biological functions.",,"['YE, RICHARD D.', 'BOULAY, FRANÇOIS', 'WANG, JI MING', 'DAHLGREN, CLAES', 'GERARD, CRAIG', 'PARMENTIER, MARC', 'SERHAN, CHARLES N.', 'MURPHY, PHILIP M.']",,,,
,PMC,Quantitative high throughput screening identifies inhibitors of anthrax-induced cell death,http://dx.doi.org/10.1016/j.bmc.2009.05.054,PMC2795356,,,"Here, we report the results of a quantitative high-throughput screen (qHTS) measuring the endocytosis and translocation of a β-lactamase-fused-lethal factor and the identification of small molecules capable of obstructing the process of anthrax toxin internalization. Several small molecules protect RAW264.7 macrophages and CHO cells from anthrax lethal toxin and protected cells from an LF-Pseudomonas exotoxin fusion protein and diphtheria toxin. Further efforts demonstrated that these compounds impaired the PA heptamer pre-pore to pore conversion in cells expressing the CMG2 receptor, but not the related TEM8 receptor, indicating that these compounds likely interfere with toxin internalization.",,"['Zhu, Ping Jun', 'Hobson, Peyton', 'Southall, Noel', 'Qiu, Cunping', 'Thomas, Craig J.', 'Lu, Jiamo', 'Inglese, James', 'Zheng, Wei', 'Leppla, Stephen H.', 'Bugge, Thomas H.', 'Austin, Christopher P.', 'Liu, Shihui']",,,,
,PMC,Conformational changes in redox pairs of protein structures,http://dx.doi.org/10.1002/pro.175,PMC2776962,,,"Disulfides are conventionally viewed as structurally stabilizing elements in proteins but emerging evidence suggests two disulfide subproteomes exist. One group mediates the well known role of structural stabilization. A second redox-active group are best known for their catalytic functions but are increasingly being recognized for their roles in regulation of protein function. Redox-active disulfides are, by their very nature, more susceptible to reduction than structural disulfides; and conversely, the Cys pairs that form them are more susceptible to oxidation. In this study, we searched for potentially redox-active Cys Pairs by scanning the Protein Data Bank for structures of proteins in alternate redox states. The PDB contains over 1134 unique redox pairs of proteins, many of which exhibit conformational differences between alternate redox states. Several classes of structural changes were observed, proteins that exhibit: disulfide oxidation following expulsion of metals such as zinc; major reorganisation of the polypeptide backbone in association with disulfide redox-activity; order/disorder transitions; and changes in quaternary structure. Based on evidence gathered supporting disulfide redox activity, we propose disulfides present in alternate redox states are likely to have physiologically relevant redox activity.",,"['Fan, Samuel W', 'George, Richard A', 'Haworth, Naomi L', 'Feng, Lina L', 'Liu, Jason Y', 'Wouters, Merridee A']",,,,
,PMC,RNA Binding by the Brome Mosaic Virus Capsid Protein and the Regulation of Viral RNA Accumulation,http://dx.doi.org/10.1016/j.jmb.2009.05.065,PMC2774812,,,"Viral capsid proteins (CPs) can regulate gene expression and encapsulate viral RNAs. Low-level expression of the brome mosaic virus (BMV) CP was found to stimulate viral RNA accumulation, while higher levels inhibited translation and BMV RNA replication. Regulation of translation acts through an RNA element named the B box, which is also critical for the replicase assembly. The BMV CP has also been shown to preferentially bind to an RNA element named SLC that contains the core promoter for genomic minus-strand RNA synthesis. To further elucidate CP interaction with RNA, Available online we used a reversible cross-linking–peptide fingerprinting assay to identify 27 May 2009 peptides in the capsid that contact the SLC, the B-box RNA, and the encapsidated RNA. Transient expression of three mutations made in residues within or close by the cross-linked peptides partially released the normal inhibition of viral RNA accumulation in agroinfiltrated Nicotiana benthamiana. Interestingly, two of the mutants, R142A and D148A, were found to retain the ability to down-regulate reporter RNA translation. These two mutants formed viral particles in inoculated leaves, but only R142Awas able to move systemically in the inoculated plant. The R142A CP was found to have higher affinities for SLC and the B box compared with those of wild-type CP and to alter contacts to the RNA in the virion. These results better define how the BMV CP can interact with RNA and regulate different viral processes.",,"['Yi, Guanghui', 'Vaughan, Robert C.', 'Yarbrough, Ian', 'Dharmaiah, S.', 'Kao, C. Cheng']",,,,
,PMC,Human Bocavirus Can Be Cultured in Differentiated Human Airway Epithelial Cells,http://dx.doi.org/10.1128/JVI.00614-09,PMC2708629,,,"In 2005, a human bocavirus was discovered in children with respiratory tract illnesses. Attempts to culture this virus on conventional cell lines has failed thus far. We investigated whether the virus can replicate on pseudostratified human airway epithelium. This cell culture system mimics the human airway environment and facilitates culturing of various respiratory agents. The cells were inoculated with human bocavirus-positive nasopharyngeal washes from children, and virus replication was monitored by measuring apical release of the virus via real-time PCR. Furthermore, we identified different viral mRNAs in the infected cells. All mRNAs were transcribed from a single promoter but varied due to alternative splicing and alternative polyadenylation, similar to what has been described for bovine parvovirus and minute virus of canines, the other two members of the Bocavirus genus. Thus, transcription of human bocavirus displays strong homology to the transcription of the other bocaviruses. In conclusion, we report here for the first time that human bocavirus can be propagated in an in vitro culture system and present a detailed map of the set of mRNAs that are produced by the virus.",,"['Dijkman, Ronald', 'Koekkoek, Sylvie M.', 'Molenkamp, Richard', 'Schildgen, Oliver', 'van der Hoek, Lia']",,,,
,PMC,Influenza virus morphogenesis and budding,http://dx.doi.org/10.1016/j.virusres.2009.05.010,PMC2730999,,,"Influenza viruses are enveloped, negative stranded, segmented RNA viruses belonging to Orthomyxoviridae family. Each virion consists of three major subviral components, namely (i) a viral envelope decorated with three transmembrane proteins hemagglutinin (HA), neuraminidase (NA) and M2, (ii) an intermediate layer of matrix protein (M1), and (iii) an innermost helical viral ribonucleocapsid [vRNP] core formed by nucleoprotein (NP) and negative strand viral RNA (vRNA). Since complete virus particles are not found inside the cell, the processes of assembly, morphogenesis, budding and release of progeny virus particles at the plasma membrane of the infected cells are critically important for the production of infectious virions and pathogenesis of influenza viruses as well. Morphogenesis and budding require that all virus components must be brought to the budding site which is the apical plasma membrane in polarized epithelial cells whether in vitro cultured cells or in vivo infected animals. HA and NA forming the outer spikes on the viral envelope possess apical sorting signals and use exocytic pathways and lipid rafts for cell surface transport and apical sorting. NP also has apical determinant(s) and is probably transported to the apical budding site similarly via lipid rafts and/or through cortical actin microfilaments. M1 binds the NP and the exposed RNAs of vRNPs, as well as to the cytoplasmic tails (CT) and transmembrane (TM) domains of HA, NA and M2, and is likely brought to the budding site on the piggy-back of vRNP and transmembrane proteins. Budding processes involve bud initiation, bud growth and bud release. Presence of lipid rafts and assembly of viral components at the budding site can cause asymmetry of lipid bilayers and outward membrane bending leading to bud initiation and bud growth. Bud release requires fusion of the apposing viral and cellular membranes and scission of the virus buds from the infected cellular membrane. The processes involved in bud initiation, bud growth and bud scission/release require involvement both viral and host components and can affect bud closing and virus release in both positive and negative ways. Among the viral components, M1, M2 and NA play important roles in bud release and M1, M2 and NA mutations all affect the morphology of buds and released viruses. Disassembly of host cortical actin microfilaments at the pinching-off site appears to facilitate bud fission and release. Bud scission is energy dependent and only a small fraction of virus buds present on the cell surface is released. Discontinuity of M1 layer underneath the lipid bilayer, absence of outer membrane spikes, absence of lipid rafts in the lipid bilayer, as well as possible presence of M2 and disassembly of cortical actin microfilaments at the pinching off site appear to facilitate bud fission and bud release. We provide our current understanding of these important processes leading to the production of infectious influenza virus particles.",,"['Nayak, Debi P.', 'Balogun, Rilwan A.', 'Yamada, Hiroshi', 'Zhou, Z. Hong', 'Barman, Subrata']",,,,
,PMC,"Label-Free, Electrical Detection of the SARS Virus N-Protein with Nanowire Biosensors Utilizing Antibody Mimics as Capture Probes",http://dx.doi.org/10.1021/nn900086c,PMC2765574,,,"Antibody mimic proteins (AMPs) are poly-peptides that bind to their target analytes with high affinity and specificity, just like conventional antibodies, but are much smaller in size (2–5 nm, less than 10kDa). In this report, we describe the first application of AMP in the field of nanobiosensors. In(2)O(3) nanowire based biosensors have been configured with an AMP (Fibronectin, Fn) to detect nucleocapsid (N) protein, a biomarker for severe acute respiratory syndrome (SARS). Using these devices, N protein was detected at sub-nanomolar concentration in the presence of 44 µM bovine serum albumin as a background. Furthermore, the binding constant of the AMP to Fn was determined from the concentration dependence of the response of our biosensors.",,"['Ishikawa, Fumiaki N.', 'Chang, Hsiao-Kang', 'Curreli, Marco', 'Liao, Hsiang-I', 'Olson, Anders C.', 'Chen, Po-Chiang', 'Zhang, Rui', 'Roberts, Richard W.', 'Sun, Ren', 'Cote, Richard J.', 'Thompson, Mark E.', 'Zhou, Chongwu']",,,,
,PMC,Airborne influenza virus detection with four aerosol samplers using molecular and infectivity assays: considerations for a new infectious virus aerosol sampler,http://dx.doi.org/10.1111/j.1600-0668.2009.00609.x,PMC3684270,,,"As a first step in conducting studies of airborne influenza transmission, we compared the collection performance of an SKC Biosampler, a compact cascade impactor (CCI), Teflon filters, and gelatin filters by collecting aerosolized influenza virus in a one-pass aerosol chamber. Influenza virus infectivity was determined using a fluorescent focus assay and influenza virus nucleic acid (originating from viable and non-viable viruses) was measured using quantitative PCR. The results showed that the SKC Biosampler recovered and preserved influenza virus infectivity much better than the other samplers – the CCI, Teflon, and gelatin filters recovered only 7–22% of infectious viruses compared with the Biosampler. Total virus collection was not significantly different among the SKC Biosampler, the gelatin, and Teflon filters, but was significantly lower in the CCI. Results from this study show that a new sampler is needed for virus aerosol sampling, as commercially available samplers do not efficiently collect and conserve virus infectivity. Applications for a new sampler include studies of airborne disease transmission and bioterrorism monitoring. Design parameters for a new sampler include high collection efficiency for fine particles and liquid sampling media to preserve infectivity.",,"['Fabian, P.', 'McDevitt, J. J.', 'Houseman, E. A.', 'Milton, D. K.']",,,,
,PMC,PATHOLOGICAL MANIFESTATIONS OF FELINE IMMUNODEFICIENCY VIRUS (FIV) INFECTION IN WILD AFRICAN LIONS,http://dx.doi.org/10.1016/j.virol.2009.04.011,PMC2771374,,,"Feline immunodeficiency virus (FIV) causes AIDS in the domestic cat (Felis catus) but has not been explicitly associated with AIDS pathology in any of the eight free-ranging species of Felidae that are endemic with circulating FIV strains. African lion (Panthera leo) populations are infected with lion-specific FIV strains (FIVple), yet there remains uncertainty about the degree to which FIV infection impacts their health. Reported CD4+ T-lymphocyte depletion in FIVple infected lions and anecdotal reports of lion morbidity associated with FIV sero-prevalence emphasize the concern as to whether FIVple is innocuous or pathogenic. Here we monitored clinical, biochemical, histological and serological parameters among FIVple-positive (N=47) as compared to FIVple negative (N=17) lions anesthetized and sampled on multiple occasions between 1999 and 2006 in Botswana. Relative to uninfected lions, FIVple infected lions displayed a significant elevation in the prevalence of AIDS defining conditions: lymphandenopathy, gingivitis, tongue papillomas, dehydration, and poor coat condition, as well as displaying abnormal red blood cell parameters and elevated liver enzymes and serum proteins. Spleen and lymph node laparoscopic biopsies from free-ranging FIVple infected lions (N=8) revealed evidence of lymphoid depletion, the hallmark pathology documented in immunodefieciency virus infections of humans (HIV-1), macaques, and domestic cats. We conclude that over time FIVple infections in free-ranging lions can lead to adverse clinical, immunological, and pathological outcomes in some individuals that parallel sequelae caused by lentivirus infection in humans (HIV), Asian macaques (SIV) and domestic cats (FIVfca).",,"['Roelke, Melody E.', 'Brown, Meredith A.', 'Troyer, Jennifer L.', 'Winterbach, Hanlie', 'Winterbach, Christiaan', 'Hemson, Graham', 'Smith, Dahlem', 'Johnson, Randall C.', 'Pecon-Slattery, Jill', 'Roca, Alfred L.', 'Alexander, Katherine', 'Klein, Lin', 'Martinelli, Paulo', 'Krishnasamu, Karthiuani', ""O'Brien, Stephen J.""]",,,,
,PMC,Poxvirus protein evolution: Family-wide assessment of possible horizontal gene transfer events,http://dx.doi.org/10.1016/j.virusres.2009.05.006,PMC2779260,,,"To investigate the evolutionary origins of proteins encoded by the Poxviridae family of viruses, we examined all poxvirus protein coding genes using a method of characterizing and visualizing the similarity between these proteins and taxonomic subsets of proteins in GenBank. Our analysis divides poxvirus proteins into categories based on their relative degree of similarity to two different taxonomic subsets of proteins such as all eukaryote vs. all virus (except poxvirus) proteins. As an example, this allows us to identify, based on high similarity to only eukaryote proteins, poxvirus proteins that may have been obtained by horizontal transfer from their hosts. Although this method alone does not definitively prove horizontal gene transfer, it allows us to provide an assessment of the possibility of horizontal gene transfer for every poxvirus protein. Potential candidates can then be individually studied in more detail during subsequent investigation. Results of our analysis demonstrate that in general, proteins encoded by members of the subfamily Chordopoxvirinae exhibit greater similarity to eukaryote proteins than to proteins of other virus families. In addition, our results reiterate the important role played by host gene capture in poxvirus evolution; highlight the functions of many genes poxviruses share with their hosts; and illustrate which host-like genes are present uniquely in poxviruses and which are also present in other virus families.",,"['Odom, Mary R.', 'Hendrickson, R. Curtis', 'Lefkowitz, Elliot J.']",,,,
,PMC,Cholesterol Supplementation During Production Increases the Infectivity of Retroviral and Lentiviral Vectors Pseudotyped with the Vesicular Stomatitis Virus Glycoprotein (VSV-G),http://dx.doi.org/10.1016/j.bej.2008.12.004,PMC2663912,,,"Cholesterol, a major component of plasma membrane lipid rafts, is important for assembly and budding of enveloped viruses, including influenza and HIV-1. Cholesterol depletion impairs virus assembly and infectivity. This study examined the effects of exogenous cholesterol addition (delivered as a complex with methyl beta cyclodextrin) on the production of Molony murine leukemia virus retroviral vector and HIV-1-based lentiviral vector pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G). Cholesterol supplementation before and during vector production enhanced the infectivity of retroviral and lentiviral vectors up to 4-fold and 6-fold, respectively. In contrast, the amount of retroviral vector produced was unchanged, and that of lentiviral vector was increased less than two-fold. Both free cholesterol and cholesterol ester content in 293-gag-pol producer cells increased with cholesterol addition. In contrast, the phospholipids headgroup composition was essentially unchanged by cholesterol supplementation in 293-gag-pol packaging cells. Based on these results, it is proposed that cholesterol supplementation increases the infectivity of VSV-G-pseudotyped retroviral and lentiviral vectors, possibly by altering the composition of the producer cell membrane where the viral vectors are assembled and bud, and/or by changing the lipid composition of the viral vectors.",,"['Chen, Yong', 'Ott, Christopher J.', 'Townsend, Kay', 'Subbaiah, Papasani', 'Aiyar, Ashok', 'Miller, William M.']",,,,
,PMC,Mechanism of Sustained Activation of Ribosomal S6 Kinase (RSK) and ERK by Kaposi Sarcoma-associated Herpesvirus ORF45: MULTIPROTEIN COMPLEXES RETAIN ACTIVE PHOSPHORYLATED ERK AND RSK AND PROTECT THEM FROM DEPHOSPHORYLATION,http://dx.doi.org/10.1074/jbc.M900025200,PMC2679495,,,"As obligate intracellular parasites, viruses exploit diverse cellular signaling machineries, including the mitogen-activated protein-kinase pathway, during their infections. We have demonstrated previously that the open reading frame 45 (ORF45) of Kaposi sarcoma-associated herpesvirus interacts with p90 ribosomal S6 kinases (RSKs) and strongly stimulates their kinase activities (Kuang, E., Tang, Q., Maul, G. G., and Zhu, F. (2008) J. Virol.82 ,1838 -185018057234). Here, we define the mechanism by which ORF45 activates RSKs. We demonstrated that binding of ORF45 to RSK increases the association of extracellular signal-regulated kinase (ERK) with RSK, such that ORF45, RSK, and ERK formed high molecular mass protein complexes. We further demonstrated that the complexes shielded active pERK and pRSK from dephosphorylation. As a result, the complex-associated RSK and ERK were activated and sustained at high levels. Finally, we provide evidence that this mechanism contributes to the sustained activation of ERK and RSK in Kaposi sarcoma-associated herpesvirus lytic replication.",,"['Kuang, Ersheng', 'Wu, Fayi', 'Zhu, Fanxiu']",,,,
,PMC,Initiation of Hepatitis C Virus Infection Requires the Dynamic  Microtubule Network: ROLE OF THE VIRAL NUCLEOCAPSID  PROTEIN,http://dx.doi.org/10.1074/jbc.M807873200,PMC2679479,,,"Early events leading to the establishment of hepatitis C virus (HCV) infection are not completely understood. We show that intact and dynamic microtubules play a key role in the initiation of productive HCV infection. Microtubules were required for virus entry into cells, as evidenced using virus pseudotypes presenting HCV envelope proteins on their surface. Studies carried out using the recent infectious HCV model revealed that microtubules also play an essential role in early, postfusion steps of the virus cycle. Moreover, low concentrations of vinblastin and nocodazol, microtubule-affecting drugs, and paclitaxel, which stabilizes microtubules, inhibited infection, suggesting that microtubule dynamic instability and/or treadmilling mechanisms are involved in HCV internalization and early transport. By protein chip and direct core-dependent pull-down assays, followed by mass spectrometry, we identified β- and α-tubulin as cellular partners of the HCV core protein. Surface plasmon resonance analyses confirmed that core directly binds to tubulin with high affinity via amino acids 2-117. The interaction of core with tubulin in vitro promoted its polymerization and enhanced the formation of microtubules. Immune electron microscopy showed that HCV core associates, at least temporarily, with microtubules polymerized in its presence. Studies by confocal microscopy showed a juxtaposition of core with microtubules in HCV-infected cells. In summary, we report that intact and dynamic microtubules are required for virus entry into cells and for early postfusion steps of infection. HCV may exploit a direct interaction of core with tubulin, enhancing microtubule polymerization, to establish efficient infection and promote virus transport and/or assembly in infected cells.",,"['Roohvand, Farzin', 'Maillard, Patrick', 'Lavergne, Jean-Pierre', 'Boulant, Steeve', 'Walic, Marine', 'Andréo, Ursula', 'Goueslain, Lucie', 'Helle, François', 'Mallet, Adeline', 'McLauchlan, John', 'Budkowska, Agata']",,,,
,PMC,Hepatitis C Virus NS5A Protein Is a Substrate for the Peptidyl-prolyl  cis/trans Isomerase Activity of Cyclophilins A and  B,http://dx.doi.org/10.1074/jbc.M809244200,PMC2679460,,,"We report here a biochemical and structural characterization of domain 2 of the nonstructural 5A protein (NS5A) from the JFH1 Hepatitis C virus strain and its interactions with cyclophilins A and B (CypA and CypB). Gel filtration chromatography, circular dichroism spectroscopy, and finally NMR spectroscopy all indicate the natively unfolded nature of this NS5A-D2 domain. Because mutations in this domain have been linked to cyclosporin A resistance, we used NMR spectroscopy to investigate potential interactions between NS5A-D2 and cellular CypA and CypB. We observed a direct molecular interaction between NS5A-D2 and both cyclophilins. The interaction surface on the cyclophilins corresponds to their active site, whereas on NS5A-D2, it proved to be distributed over the many proline residues of the domain. NMR heteronuclear exchange spectroscopy yielded direct evidence that many proline residues in NS5A-D2 form a valid substrate for the enzymatic peptidyl-prolyl cis/trans isomerase (PPIase) activity of CypA and CypB.",,"['Hanoulle, Xavier', 'Badillo, Aurélie', 'Wieruszeski, Jean-Michel', 'Verdegem, Dries', 'Landrieu, Isabelle', 'Bartenschlager, Ralf', 'Penin, François', 'Lippens, Guy']",,,,
,PMC,KIR genotype predicts the capacity of human KIR(+) CD56(dim) NK cells to respond to pathogen-associated signals,http://dx.doi.org/10.4049/jimmunol.0804224,PMC2854670,,,"IFN-γ emanating from natural killer (NK) cells is an important component of innate defence against infection. Here we demonstrate that, following in vitro stimulation of human peripheral blood NK cells with a variety of microbial ligands, CD56(dim) as well as CD56(bright) NK cells contribute to the overall NK cell IFN-γ response with, for most cell donors, IFN-γ(+) CD56(dim) NK cells outnumbering IFN-γ(+) CD56(bright) NK cells. We also observe that the magnitude of the human NK IFN-γ response to microbial ligands varies between individuals; that the antimicrobial response of CD56(bright), but not CD56(dim), NK cells is highly correlated with that of myeloid accessory cells; and that the ratio of IFN-γ(+) CD56(dim) to IFN-γ(+) CD56(bright) NK cells following microbial stimulation differs between individuals but remains constant for a given donor over time. Furthermore, ratios of IFN-γ(+) CD56(dim) to IFN-γ(+) CD56(bright) NK cells for different microbial stimuli are highly correlated and the relative response of CD56(dim) and CD56(bright) NK cells is highly significantly associated with killer immunoglobulin-like receptor (KIR) genotype. These data reveal an influence of KIR genotype, possibly mediated via NK cell licensing, on the ability of NK cells to respond to non-viral infections and have implications for genetic regulation of susceptibility to infection in humans.",,"['Korbel, Daniel S.', 'Norman, Paul J.', 'Newman, Kirsty C.', 'Horowitz, Amir', 'Gendzekhadze, Ketevan', 'Parham, Peter', 'Riley, Eleanor M.']",,,,
,PMC,Human Adenovirus 14a: A New Epidemic Threat,http://dx.doi.org/10.1086/598522,PMC2748061,,,,,"['Gray, Gregory C.', 'Chorazy, Margaret L.']",,,,
,PMC,Characterization of a Highly Conserved Domain within the Severe Acute Respiratory Syndrome Coronavirus Spike Protein S2 Domain with Characteristics of a Viral Fusion Peptide,http://dx.doi.org/10.1128/JVI.00079-09,PMC2708636,,,"Many viral fusion proteins are primed by proteolytic cleavage near their fusion peptides. While the coronavirus (CoV) spike (S) protein is known to be cleaved at the S1/S2 boundary, this cleavage site is not closely linked to a fusion peptide. However, a second cleavage site has been identified in the severe acute respiratory syndrome CoV (SARS-CoV) S2 domain (R797). Here, we investigated whether this internal cleavage of S2 exposes a viral fusion peptide. We show that the residues immediately C-terminal to the SARS-CoV S2 cleavage site SFIEDLLFNKVTLADAGF are very highly conserved across all CoVs. Mutagenesis studies of these residues in SARS-CoV S, followed by cell-cell fusion and pseudotyped virion infectivity assays, showed a critical role for residues L803, L804, and F805 in membrane fusion. Mutation of the most N-terminal residue (S798) had little or no effect on membrane fusion. Biochemical analyses of synthetic peptides corresponding to the proposed S2 fusion peptide also showed an important role for this region in membrane fusion and indicated the presence of α-helical structure. We propose that proteolytic cleavage within S2 exposes a novel internal fusion peptide for SARS-CoV S, which may be conserved across the Coronaviridae.",,"['Madu, Ikenna G.', 'Roth, Shoshannah L.', 'Belouzard, Sandrine', 'Whittaker, Gary R.']",,,,
,PMC,Coronavirus Genetically Redirected to the Epidermal Growth Factor Receptor Exhibits Effective Antitumor Activity against a Malignant Glioblastoma,http://dx.doi.org/10.1128/JVI.00495-09,PMC2708613,,,"Coronaviruses are positive-strand RNA viruses with features attractive for oncolytic therapy. To investigate this potential, we redirected the coronavirus murine hepatitis virus (MHV), which is normally unable to infect human cells, to human tumor cells by using a soluble receptor (soR)-based expression construct fused to an epidermal growth factor (EGF) receptor targeting moiety. Addition of this adapter protein to MHV allowed infection of otherwise nonsusceptible, EGF receptor (EGFR)-expressing cell cultures. We introduced the sequence encoding the adaptor protein soR-EGF into the MHV genome to generate a self-targeted virus capable of multiround infection. The resulting recombinant MHV was viable and had indeed acquired the ability to infect all glioblastoma cell lines tested in vitro. Infection of malignant human glioblastoma U87ΔEGFR cells gave rise to release of progeny virus and efficient cell killing in vitro. To investigate the oncolytic capacity of the virus in vivo, we used an orthotopic U87ΔEGFR xenograft mouse model. Treatment of mice bearing a lethal intracranial U87ΔEGFR tumor by injection with MHVsoR-EGF significantly prolonged survival compared to phosphate-buffered saline-treated (P = 0.001) and control virus-treated (P = 0.004) animals, and no recurrent tumor load was observed. However, some adverse effects were seen in normal mouse brain tissues that were likely caused by the natural murine tropism of MHV. This is the first demonstration of oncolytic activity of a coronavirus in vivo. It suggests that nonhuman coronaviruses may be attractive new therapeutic agents against human tumors.",,"['Verheije, Monique H.', 'Lamfers, Martine L. M.', 'Würdinger, Thomas', 'Grinwis, Guy C. M.', 'Gerritsen, Winald R.', 'van Beusechem, Victor W.', 'Rottier, Peter J. M.']",,,,
,PMC,Control of antibiotic-resistant bacteria in the office and clinic,http://dx.doi.org/10.1503/cmaj.071891,PMC2679832,,,,,"['Matlow, Anne G.', 'Morris, Shaun K.']",,,,
,PMC,Digital Disease Detection — Harnessing the Web for Public Health Surveillance,http://dx.doi.org/10.1056/NEJMp0900702,PMC2917042,,,,,"['Brownstein, John S.', 'Freifeld, Clark C.', 'Madoff, Lawrence C.']",,,,
,PMC,"Differential signal transduction, membrane trafficking, and immune effector functions mediated by FcγRI versus FcγRIIa",http://dx.doi.org/10.1182/blood-2008-10-184457,PMC4937993,,,"Receptors for the fragment crystallizable region of immunoglobulin-G (FcγRS) play an important role in linking the humoral and cellular arms of the immune response. In this study, we present a comprehensive functional comparison of 2 human Fc-receptors, FcγRI and FcγRIIa. Activation of FcγRI results in a novel signaling cascade that links phospholipase D1 to sphingosine kinase-1 in U937 cells and primary human monocytes. This induces the expression of proinflammatory mediators and is associated with trafficking of immune complexes into human leukocyte antigen-DM positive antigen-processing compartments coupled with improved MHC class II–mediated antigen presentation to T lymphocytes. In contrast, activation of FcγRIIa elicits signaling through phospholipase Cγ1, resulting in increases in intracellular calcium, activation of nicotinamide adenine dinucleotide phosphateoxidative burst, and differential membrane trafficking combined with impaired antigen presentation and proinflammatory cytokine expression. These data provide a mechanistic insight into the disparate activities associated with Fc receptors in immunity, namely, reinforcement of immune responses through stimulation of proinflammatory signaling and antigen presentation, versus the maintenance of immunologic homeostasis through the noninflammatory clearance of immune complexes.",,"['Dai, Xilei', 'Jayapal, Manikandan', 'Tay, Hwee Kee', 'Reghunathan, Renji', 'Lin, Gen', 'Too, Chien Tei', 'Lim, Yan Ting', 'Chan, Soh Ha', 'Kemeny, D. Michael', 'Floto, R. Andres', 'Smith, Kenneth G. C.', 'Melendez, Alirio J.', 'MacAry, Paul A.']",,,,
,PMC,Identification of In Vivo-Interacting Domains of the Murine Coronavirus Nucleocapsid Protein,http://dx.doi.org/10.1128/JVI.00440-09,PMC2704785,,,"The coronavirus nucleocapsid protein (N), together with the large, positive-strand RNA viral genome, forms a helically symmetric nucleocapsid. This ribonucleoprotein structure becomes packaged into virions through association with the carboxy-terminal endodomain of the membrane protein (M), which is the principal constituent of the virion envelope. Previous work with the prototype coronavirus mouse hepatitis virus (MHV) has shown that a major determinant of the N-M interaction maps to the carboxy-terminal domain 3 of the N protein. To explore other domain interactions of the MHV N protein, we expressed a series of segments of the MHV N protein as fusions with green fluorescent protein (GFP) during the course of viral infection. We found that two of these GFP-N-domain fusion proteins were selectively packaged into virions as the result of tight binding to the N protein in the viral nucleocapsid, in a manner that did not involve association with either M protein or RNA. The nature of each type of binding was further explored through genetic analysis. Our results defined two strongly interacting regions of the N protein. One is the same domain 3 that is critical for M protein recognition during assembly. The other is domain N1b, which corresponds to the N-terminal domain that has been structurally characterized in detail for two other coronaviruses, infectious bronchitis virus and the severe acute respiratory syndrome coronavirus.",,"['Hurst, Kelley R.', 'Koetzner, Cheri A.', 'Masters, Paul S.']",,,,
,PMC,Early Upregulation of Acute Respiratory Distress Syndrome-Associated Cytokines Promotes Lethal Disease in an Aged-Mouse Model of Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/JVI.00127-09,PMC2704758,,,"Several respiratory viruses, including influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV), produce more severe disease in the elderly, yet the molecular mechanisms governing age-related susceptibility remain poorly studied. Advanced age was significantly associated with increased SARS-related deaths, primarily due to the onset of early- and late-stage acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Infection of aged, but not young, mice with recombinant viruses bearing spike glycoproteins derived from early human or palm civet isolates resulted in death accompanied by pathological changes associated with ARDS. In aged mice, a greater number of differentially expressed genes were observed than in young mice, whose responses were significantly delayed. Differences between lethal and nonlethal virus phenotypes in aged mice could be attributed to differences in host response kinetics rather than virus kinetics. SARS-CoV infection induced a range of interferon, cytokine, and pulmonary wound-healing genes, as well as several genes associated with the onset of ARDS. Mice that died also showed unique transcriptional profiles of immune response, apoptosis, cell cycle control, and stress. Cytokines associated with ARDS were significantly upregulated in animals experiencing lung pathology and lethal disease, while the same animals experienced downregulation of the ACE2 receptor. These data suggest that the magnitude and kinetics of a disproportionately strong host innate immune response contributed to severe respiratory stress and lethality. Although the molecular mechanisms governing ARDS pathophysiology remain unknown in aged animals, these studies reveal a strategy for dissecting the genetic pathways by which SARS-CoV infection induces changes in the host response, leading to death.",,"['Rockx, Barry', 'Baas, Tracey', 'Zornetzer, Gregory A.', 'Haagmans, Bart', 'Sheahan, Timothy', 'Frieman, Matthew', 'Dyer, Matthew D.', 'Teal, Thomas H.', 'Proll, Sean', 'van den Brand, Judith', 'Baric, Ralph', 'Katze, Michael G.']",,,,
,PMC,Antigenicity and immunogenicity of SARS-CoV S protein receptor-binding domain stably expressed in CHO cells,http://dx.doi.org/10.1016/j.bbrc.2009.05.003,PMC2750803,,,"The receptor-binding domain (RBD) of SARS coronavirus (SARS-CoV) spike (S) protein contains multiple conformation-dependent epitopes that induce neutralizing antibody responses. Here we used CHO-K1 cells to establish a cell line for stable expression of a 193-mer (residues 318–510) RBD (RBD193-CHO) and determined its antigenicity and immunogenicity. We found that RBD193-CHO reacted strongly with a panel of six monoclonal antibodies recognizing various conformational and linear epitopes in RBD, suggesting that this recombinant protein maintains intact conformation and good antigenicity. Immunization of mice with RBD193-CHO resulted in induction of high titers of RBD-specific neutralizing antibodies and potent IL-4-expressing T cell responses. RBD193-CHO induced immunity that protected a majority of the vaccinated mice from SARS-CoV challenge. These results suggest that the recombinant RBD produced in an established stable cell line maintains strong immunogenicity with high potential for use as an effective and economic subunit SARS vaccine.",,"['Du, Lanying', 'Zhao, Guangyu', 'Li, Lin', 'He, Yuxian', 'Zhou, Yusen', 'Zheng, Bo-Jian', 'Jiang, Shibo']",,,,
,PMC,The Biology of Persistent Infection: Inflammation and Demyelination following Murine Coronavirus Infection of the Central Nervous System,http://dx.doi.org/10.2174/157339509789504005,PMC2782875,,,"Multiple Sclerosis (MS) is an immune-mediated demyelinating disease of humans. Although causes of MS are enigmatic, underlying elements contributing to disease development include both genetic and environmental factors. Recent epidemiological evidence has pointed to viral infection as a trigger to initiating white matter damage in humans. Mouse hepatitis virus (MHV) is a positive strand RNA virus that, following intracranial infection of susceptible mice, induces an acute encephalomyelitis that later resolves into a chronic fulminating demyelinating disease. Immune cell infiltration into the central nervous system is critical both to quell viral replication and instigate demyelination. Recent efforts by our laboratory and others have focused upon strategies capable of enhancing remyelination in response to viral-induced demyelination, both by dampening chronic inflammation and by surgical engraftment of remyelination – competent neural precursor cells.",,"['Hosking, Martin P.', 'Lane, Thomas E.']",,,,
,PMC,Disaster planning: Potential effects of an influenza pandemic on community healthcare resources,,PMC3757092,,,"The federal government states that local communities are primarily responsible for public health planning and implementation during a severe pandemic. Accordingly, an assessment of the current healthcare capabilities in these communities and planning for deficiencies is required. This article assesses the impact and healthcare capabilities of a specific model local community in a mid-Atlantic state. Two statistical models demonstrate the likely impact of both mild and severe pandemics on local healthcare resources. Both models reveal significant deficiencies that local communities may face. In the event of a severe 1918-type pandemic influenza or a mild influenza pandemic, many local community healthcare systems will likely have inadequate resources to respond to the crisis; such a healthcare emergency would likely overwhelm local community resources and current public health practices. Proper planning at the community level is critical for being truly prepared for such a public health emergency.",,"['Mareiniss, Darren P.', 'Hirshon, Jon Mark', 'Thibodeau, Bryan C.']",,,,
,PMC,Ectodomain shedding of angiotensin converting enzyme 2 in human airway epithelia,http://dx.doi.org/10.1152/ajplung.00071.2009,PMC2711803,,,"Angiotensin-converting enzyme 2 (ACE2) is a terminal carboxypeptidase and the receptor for the SARS and NL63 coronaviruses (CoV). Loss of ACE2 function is implicated in severe acute respiratory syndrome (SARS) pathogenesis, but little is known about ACE2 biogenesis and activity in the airways. We report that ACE2 is shed from human airway epithelia, a site of SARS-CoV infection. The regulation of ACE2 release was investigated in polarized human airway epithelia. Constitutive generation of soluble ACE2 was inhibited by DPC 333, implicating a disintegrin and metalloprotease 17 (ADAM17). Phorbol ester, ionomycin, endotoxin, and IL-1β and TNFα acutely induced ACE2 release, further supporting that ADAM17 and ADAM10 regulate ACE2 cleavage. Soluble ACE2 was enzymatically active and partially inhibited virus entry into target cells. We determined that the ACE2 cleavage site resides between amino acid 716 and the putative transmembrane domain starting at amino acid 741. To reveal structural determinants underlying ACE2 release, several mutant and chimeric ACE2 proteins were engineered. Neither the juxtamembrane stalk region, transmembrane domain, nor the cytosolic domain was needed for constitutive ACE2 release. Interestingly, a point mutation in the ACE2 ectodomain, L584A, markedly attenuated shedding. The resultant ACE2-L584A mutant trafficked to the cell membrane and facilitated SARS-CoV entry into target cells, suggesting that the ACE2 ectodomain regulates its release and that residue L584 might be part of a putative sheddase “recognition motif.” Thus ACE2 must be cell associated to serve as a CoV receptor and soluble ACE2 might play a role in modifying inflammatory processes at the airway mucosal surface.",,"['Jia, Hong Peng', 'Look, Dwight C.', 'Tan, Ping', 'Shi, Lei', 'Hickey, Melissa', 'Gakhar, Lokesh', 'Chappell, Mark C.', 'Wohlford-Lenane, Christine', 'McCray, Paul B.']",,,,
,PMC,Localization of Low-Density Detergent-Resistant Membrane Proteins in Intact and Acrosome-Reacted Mouse Sperm,http://dx.doi.org/10.1095/biolreprod.108.075242,PMC2804839,,,"Mammalian sperm become fertile after completing capacitation, a process associated with cholesterol loss and changes in the biophysical properties of the sperm membranes that prepares the sperm to undergo the acrosome reaction. Different laboratories have hypothesized that cholesterol efflux can influence the extent and/or movement of lipid raft microdomains. In a previous study, our laboratory investigated the identity of sperm proteins putatively associated with rafts. After extraction with Triton X-100 and ultracentrifugation in sucrose gradients, proteins distributing to the light buoyant-density fractions were cored from polyacrylamide gels and microsequenced. In this study, a subset of these proteins (TEX101, basigin, hexokinase 1, facilitated glucose transporter 3, IZUMO, and SPAM1) and other molecules known to be enriched in membrane rafts (caveolin 2, flotillin 1, flotillin 2, and the ganglioside GM3) were selected to investigate their localization in the sperm and their behavior during capacitation and the acrosome reaction. These molecules localize to multiple sperm domains, including the acrosomal cap (IZUMO, caveolin 2, and flotillin 2), equatorial segment (GM3), cytoplasmic droplet (TEX101), midpiece (basigin, facilitated glucose transporter 3, and flotillin 2), and principal piece (facilitated glucose transporter 3). Some of these markers modified their immunofluorescence pattern after sperm incubation under capacitating conditions, and these changes correlated with the occurrence of the acrosome reaction. While GM3 and caveolin 2 were not detected after the acrosome reaction, flotillin 2 was found in the equatorial segment of acrosome-reacted sperm, and IZUMO distributed along the sperm head, reaching the post- and para-acrosomal areas. Taking into consideration the requirement of the acrosome reaction for sperm to become fusogenic, these results suggest that membrane raft dynamics may have a role in sperm-egg membrane interaction.",,"['Miranda, Patricia V.', 'Allaire, Alicia', 'Sosnik, Julian', 'Visconti, Pablo E.']",,,,
,PMC,Resistance to Lipopolysaccharide-Induced Preterm Delivery Mediated by Regulatory T Cell Function in Mice,http://dx.doi.org/10.1095/biolreprod.108.074294,PMC2804837,,,"Intrauterine or intraperitoneal administration of lipopolysaccharide (LPS) into normal mice at midgestation induces preterm delivery (PTD) within 24 h through a mechanism dependent on Toll-like receptor signaling and expression of inflammatory cytokines. The exact participants in the cellular network involved in PTD are not known. Although the activities of innate immune cells are thought to be important, the extent to which this process depends on T and B cells has yet to be examined. Mice deficient in T and B cells due to genetic deficiency in the recombination activating gene 1 (Rag1(−/−)) were given LPS intraperitoneally on Day 15 of gestation and found to be susceptible to LPS-induced PTD. This was found to involve many of the inflammatory mediators reported as important in normal mice. Moreover, at a low dose (3 μg), pregnant Rag1(−/−) mice were found to be more susceptible to PTD than a cohort of normal mice on the same genetic background. This increased susceptibility was partially reversed by transfer, on Day 10 of gestation, of whole lymphocytes or purified CD4(+) T cells. Transfer of purified CD4(+) T cells to Rag1(−/−) mice resulted in a uterine draining node population of FOXP3(+) cells, suggesting that these cells may contribute to resistance to LPS-induced PTD. Overall, the data suggest that, although T and B lymphocytes are not critical positive regulators of LPS-induced PTD, CD4(+) T cells play a protective and regulatory role, and thus could be a target for preventive or therapeutic manipulation.",,"['Bizargity, Peyman', 'Del Rio, Roxana', 'Phillippe, Mark', 'Teuscher, Cory', 'Bonney, Elizabeth A.']",,,,
,PMC,"The Psychological Impact of the SARS Epidemic on Hospital Employees in China: Exposure, Risk Perception, and Altruistic Acceptance of Risk",,PMC3780353,,,"OBJECTIVE: We examined the psychological impact of the 2003 outbreak of severe acute respiratory syndrome (SARS) on hospital employees in Beijing, China. METHODS: In 2006, randomly selected employees (n = 549) of a hospital in Beijing were surveyed concerning their exposure to the 2003 SARS outbreak, and the ways in which the outbreak had affected their mental health. RESULTS: About 10% of the respondents had experienced high levels of posttraumatic stress (PTS) symptoms since the SARS outbreak. Respondents who had been quarantined, or worked in high-risk locations such as SARS wards, or had friends or close relatives who contracted SARS, were 2 to 3 times more likely to have high PTS symptom levels, than those without these exposures. Respondents’ perceptions of SARS-related risks were significantly positively associated with PTS symptom levels and partially mediated the effects of exposure. Altruistic acceptance of work-related risks was negatively related to PTS levels. CONCLUSIONS: The psychological impact of stressful events related to an infectious disease outbreak may be mediated by peoples’ perceptions of those events; altruism may help to protect some health care workers against these negative impacts.",,"['Wu, Ping', 'Fang, Yunyun', 'Guan, Zhiqiang', 'Fan, Bin', 'Kong, Junhui', 'Yao, Zhongling', 'Liu, Xinhua', 'Fuller, Cordelia J', 'Susser, Ezra', 'Lu, Jin', 'Hoven, Christina W']",,,,
,PMC,Posttranscriptional Regulatory Elements Enhance Antigen Expression and DNA Vaccine Efficacy,http://dx.doi.org/10.1089/dna.2009.0862,PMC2719066,,,"In higher eukaryotes, introns are usually required for efficient pre-mRNA processing. However, some viruses have alternative approaches involving posttranscriptional regulatory elements (PREs) to enhance intronless heterologous gene expression through enabling stability and 3′ end formation, and to facilitate the nucleocytoplasmic export of unspliced mRNAs. In the current study, we compared the human cytomegalovirus (hCMV) immediate/early (IE) intronA, as well as virus-derived PREs—the PRE of Hepatitis B virus (HPRE) and Woodchuck Hepatitis virus (WPRE) on their ability to enhance antigen gene expression in vitro and immune responses induced by DNA vaccination in animal. Among all the constructs, the plasmids carrying the HPRE element showed the highest gene expression level in both in vivo and in vitro models. During immunization of mice with low doses (10 μg) of HIV-1 DNA vaccine, only −intronA/+HPRE and +intronA/+HPRE vaccine constructs induced anti-Gag antibodies, although the −intronA/+WPRE construct also elicited antigen-specific cellular immune responses. In addition, pInHGag (+intronA/+HPRE) at a 10 μg dose could induce higher anti-Gag antibody level than that induced by pGag (−intronA/−HPRE) or pInGag (+intronA/−HPRE) at 40 μg dose (p < 0.05). Our data are useful for the optimization of heterologous expression and immunogenicity of DNA vaccines.",,"['Sun, Jing', 'Li, Dingfeng', 'Hao, Yanling', 'Zhang, Yuwei', 'Fan, Wenling', 'Fu, Jingjing', 'Hu, Yunzhang', 'Liu, Yong', 'Shao, Yiming']",,,,
,PMC,"Nature, artifice and emerging diseases",http://dx.doi.org/10.1038/embor.2009.85,PMC2680892,,,,,"Danchin, Antoine",,,,
,PMC,Estimation of the serial interval of influenza,http://dx.doi.org/10.1097/EDE.0b013e31819d1092,PMC3057478,,,"BACKGROUND: Estimates of the clinical-onset serial interval of human influenza infection (time between onset of symptoms in an index case and a secondary case) are used to inform public health policy and to construct mathematical models of influenza transmission. We estimate the serial interval of laboratory-confirmed influenza transmission in households. METHODS: Index cases were recruited after reporting to a primary healthcare center with symptoms. Members of their households were followed up with repeated home visits. RESULTS: Assuming a Weibull model and accounting for selection bias inherent in our field study design, we used symptom-onset times from 14 pairs of infector/infectee to estimate a mean serial interval of 3.6 days (95% confidence interval = 2.9–4.3 days), with standard deviation 1.6 days. CONCLUSION: The household serial interval of influenza may be longer than previously estimated. Studies of the complete serial interval, based on transmission in all community contexts, are a priority.",,"['Cowling, Benjamin J.', 'Fang, Vicky J.', 'Riley, Steven', 'Peiris, J. S. Malik', 'Leung, Gabriel M.']",,,,
,PMC,Clonal dissection of the human memory B cell repertoire following infection and vaccination,http://dx.doi.org/10.1002/eji.200839129,PMC3864550,,,"The analysis of the human memory B cell repertoire is of both fundamental and practical significance. We developed a simple method for the selective activation of memory B cells in total fresh or frozen PBMC using a combination of R848 and IL-2. In these conditions 30–40% of memory B cells generated clones producing on average 200 ng IgG in 10 days. This method was used to measure the frequency of antigen specific memory B cells as well as the fine specificity, crossreactivity and neutralizing activity of the secreted antibodies. Following influenza vaccination, specific B cells expanded dramatically, reaching up to 50% of total clonable memory B cells on day 14. Specific B cell expansions were detected also in individuals that did not show a significant serological response. Dynamic changes and persistence of B cells specific for a variety of pathogens were documented in serial PBMC samples collected over almost two decades. These results reveal novel aspects of memory B cell kinetics and provide a powerful tool to monitor immune responses following infection and vaccination.",,"['Pinna, Debora', 'Corti, Davide', 'Jarrossay, David', 'Sallusto, Federica', 'Lanzavecchia, Antonio']",,,,
,PMC,Proteomic and immunologic analyses of brain tumor exosomes,http://dx.doi.org/10.1096/fj.08-122184,PMC2669426,,,"Brain tumors are horrific diseases with almost universally fatal outcomes; new therapeutics are desperately needed and will come from improved understandings of glioma biology. Exosomes are endosomally derived 30–100 nm membranous vesicles released from many cell types into the extracellular milieu; surprisingly, exosomes are virtually unstudied in neuro-oncology. These microvesicles were used as vaccines in other tumor settings, but their immunological significance is unevaluated in brain tumors. Our purpose here is to report the initial biochemical, proteomic, and immunological studies on murine brain tumor exosomes, following known procedures to isolate exosomes. Our findings show that these vesicles have biophysical characteristics and proteomic profiles similar to exosomes from other cell types but that brain tumor exosomes have unique features (e.g., very basic isoelectric points, expressing the mutated tumor antigen EGFRvIII and the putatively immunosuppressive cytokine TGF-β). Administration of such exosomes into syngeneic animals produced both humoral and cellular immune responses in immunized hosts capable of rejecting subsequent tumor challenges but failed to prolong survival in established orthotopic models. Control animals received saline or cell lysate vaccines and showed no antitumor responses. Exosomes and microvesicles isolated from sera of patients with brain tumors also possess EGFR, EGFRvIII, and TGF-β. We conclude that exosomes released from brain tumor cells are biochemically/biophysically like other exosomes and have immune-modulating properties. They can escape the blood-brain barrier, with potential systemic and distal signaling and immune consequences.—Graner, M. W., Alzate, O., Dechkovskaia, A. M., Keene, J. D., Sampson, J. H., Mitchell, D. A., Bigner, D. D. Proteomic and immunologic analyses of brain tumor exosomes.",,"['Graner, Michael W.', 'Alzate, Oscar', 'Dechkovskaia, Angelika M.', 'Keene, Jack D.', 'Sampson, John H.', 'Mitchell, Duane A.', 'Bigner, Darell D.']",,,,
,PMC,Infiltrating Cells and IFNγ Production in the Injected Eye After Uniocular Anterior Chamber Inoculation of HSV-1,http://dx.doi.org/10.1167/iovs.08-2874,PMC4024191,,,"PURPOSE: Following uniocular anterior chamber (AC) inoculation of HSV-1, the anterior segment of the injected eye becomes inflamed and infected; however, virus does not spread from the anterior segment and infect the retina of the injected eye. The purpose of this study was to identify early infiltrating cells and to determine if infiltrating cells produced interferon γ (IFNγ). METHODS: Euthymic, female, BALB/c mice were injected in one AC with 3 × 10(4) PFU of HSV-1 (KOS) in a volume of 2µl. Mice from each group were sacrificed at 12, 24, 36, 48, and 72 hrs post injection (p.i.), the eyes were enucleated and frozen sections were stained with antibodies specific for IFNγ, Mac-1 (CD11b), CD49b, F4/80, CD4, CD8 and CD11c. The same antibodies were also used to stain single cell suspensions of ocular cells for flow cytometry. RESULTS: In the anterior segment of the injected eye, the ciliary body and iris were virus infected and inflamed, and infiltrating cells increased throughout the period of observation. Mac-1+, CD49b+ and F4/80+ cells co-localized with IFNγ in the anterior segment as early as 12hrs p.i., and the percentage of Mac-1+ cells increased in the injected eye beginning at 24hrs p.i. and continued to 72hrs p.i. CONCLUSIONS: Taken together, these results demonstrate that activated microglia are important IFNγ producing cells in the injected eye before day 3 and suggest that IFNγ produced by these cells may be involved in inhibition of anterior to posterior spread of virus in the injected eye.",,"['Cathcart, Heather M.', 'Fields, Mark A.', 'Zheng, Mei', 'Marshall, Brendan', 'Atherton, Sally S.']",,,,
,PMC,A PCR-Based Strategy for Detection of Mouse Parvovirus,,PMC2696828,,,"Mouse parvovirus (MPV) infection is difficult to address because it is asymptomatic, persists for as long as 9 wk, and occurs in small subpopulations of mice. The efficacy of a PCR-based cage swabbing strategy for MPV detection was tested. On postinoculation days (PID) 3 through 63, feces were collected from MPV-infected SW mice or the wire bars and cage wall above and below the bedding were swabbed. MPV DNA was detected in all cages in all locations on PID 7 and 14 but only below the bedding on PID 21. Swabbing below the bedding detected MPV in most cages through PID 42. Sentinels exposed to soiled cages on PID 7 and 14 but not on PID 21 seroconverted. MPV was detected in feces from all cages until PID 33 and in at least 1 cage until PID 56. In BALB/c mice, MPV was detected in feces and on cage swabs on PID 5 to 14, and 80% of sentinels exposed to soiled cages on PID 7 and 14 seroconverted. In comparison, MPV infection of C57BL/6 mice was detected in feces on PID 5 to 14 and on swabs on PID 5 and 7, and 30% of sentinels exposed to soiled cages on PID 7 and 14 seroconverted. Swabbing of multiple cages in rows in which only 1 cage contained MPV-infected mice was ineffective. In conclusion, swabbing of individual cages can be used in a genotype-dependent manner as an adjunct to soiled bedding sentinels during the first 2 wk of infection.",,"['Macy, James D', 'Paturzo, Frank X', 'Ball-Goodrich, Lisa J', 'Compton, Susan R']",,,,
,PMC,Generation of Cubic Membranes by Controlled Homotypic Interaction of  Membrane Proteins in the Endoplasmic  Reticulum,http://dx.doi.org/10.1074/jbc.M900220200,PMC2673273,,,"Cell membranes predominantly consist of lamellar lipid bilayers. When studied in vitro, however, many membrane lipids can exhibit non-lamellar morphologies, often with cubic symmetries. An open issue is how lipid polymorphisms influence organelle and cell shape. Here, we used controlled dimerization of artificial membrane proteins in mammalian tissue culture cells to induce an expansion of the endoplasmic reticulum (ER) with cubic symmetry. Although this observation emphasizes ER architectural plasticity, we found that the changed ER membrane became sequestered into large autophagic vacuoles, positive for the autophagy protein LC3. Autophagy may be targeting irregular membrane shapes and/or aggregated protein. We suggest that membrane morphology can be controlled in cells.",,"['Lingwood, Daniel', 'Schuck, Sebastian', 'Ferguson, Charles', 'Gerl, Mathias J.', 'Simons, Kai']",,,,
,PMC,Target Dependent B7-H1 Regulation Contributes to Clearance of CNS Infection and Dampens Morbidity,http://dx.doi.org/10.4049/jimmunol.0803557,PMC2909606,,,"The neurotropic coronavirus JHMV persists in oligodendroglia despite the presence of virus-specific CD8 T cells. Expression of programmed death-1 (PD-1) and B7-H1 were studied during acute and persistent infection to examine if this negative regulatory mechanism contributes to CNS viral persistence. The majority of CNS infiltrating CD8 T cells expressed PD-1, with highest levels on virus-specific CD8 T cells. Moreover, despite control of infectious virus, CD8 T cells within the CNS of persistently infected mice maintained high PD-1 expression. Analysis of virus susceptible target cells in vivo revealed that B7-H1 expression was regulated in a cell type dependent manner. Oligodendroglia and microglia up-regulated B7-H1 following infection; however, while B7-H1 expression on oligodendroglia was prominent and sustained, it was significantly reduced and transient on microglia. Infection of mice deficient in IFN-γ or IFN-α/β receptor demonstrated B7-H1 expression on oligodendroglia is predominantly regulated by IFN-γ. Antibody blockade of B7-H1 on oligodendroglia in vitro enhanced IFN-γ secretion by virus-specific CD8 T cells. More efficient virus control within the CNS of B7-H1 deficient mice confirmed inhibition of CD8 T cell function in vivo. Nevertheless, the absence of B7-H1 significantly increased morbidity without altering demyelination. These data are the first to demonstrate glia cell type dependent B7-H1 regulation in vivo, resulting in adverse effects on antiviral CD8 T cell function. However, the beneficial role of PD-1:B7-H1 interactions in limiting morbidity highlight the need to evaluate tissue specific intervention strategies.",,"['Phares, Timothy W.', 'Ramakrishna, Chandran', 'Parra, Gabriel I.', 'Epstein, Alan', 'Chen, Lieping', 'Atkinson, Roscoe', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.']",,,,
,PMC,Coronavirus Infection and Hospitalizations for Acute Respiratory Illness in Young Children,http://dx.doi.org/10.1002/jmv.21443,PMC2767383,,,"PROBLEM: There is only limited knowledge on the burden of disease due to both new (HCoV-NL63 and HKU-1) and previously discovered coronaviruses (OC43 and 229E) in children. METHOD OF STUDY: Respiratory specimens and clinical data were prospectively collected in an active, population-based surveillance study over a two-year period from children aged <5 years hospitalized with acute respiratory symptoms or fever. These samples were retrospectively tested by real-time RT-PCR for HCoV-NL63, HKU1, OC43 and 229E. RESULTS: Human coronaviruses (HCoVs) were identified in 2.2% of study children <2 years of age. Rates of HCoV-associated hospitalization per 10,000 were 10.2 (95% CI 4.3, 17.6), 4.2 (95% CI 1.9, 6.9), and 0 (95% CI 0, 3.7) in children aged <6 months, 6-23 months, and 24-59 months, respectively. CONCLUSION: Coronaviruses were identified in a modest number of hospitalized children.",,"['Talbot, H. Keipp B.', 'Crowe, James E.', 'Edwards, Kathryn M.', 'Griffin, Marie R.', 'Zhu, Yuwei', 'Weinberg, Geoffrey A.', 'Szilagyi, Peter G.', 'Hall, Caroline B.', 'Podsiad, Amy B', 'Iwane, Marika', 'Williams, John V.']",,,,
,PMC,Incubation periods of acute respiratory viral infections: a systematic review,http://dx.doi.org/10.1016/S1473-3099(09)70069-6,PMC4327893,,,"Knowledge of the incubation period is essential in the investigation and control of infectious disease, but statements of incubation period are often poorly referenced, inconsistent, or based on limited data. In a systematic review of the literature on nine respiratory viral infections of public-health importance, we identified 436 articles with statements of incubation period and 38 with data for pooled analysis. We fitted a log-normal distribution to pooled data and found the median incubation period to be 5·6 days (95% CI 4·8–6·3) for adenovirus, 3·2 days (95% CI 2·8–3·7) for human coronavirus, 4·0 days (95% CI 3·6–4·4) for severe acute respiratory syndrome coronavirus, 1·4 days (95% CI 1·3–1·5) for influenza A, 0·6 days (95% CI 0·5–0·6) for influenza B, 12·5 days (95% CI 11·8–13·3) for measles, 2·6 days (95% CI 2·1–3·1) for parainfluenza, 4·4 days (95% CI 3·9–4·9) for respiratory syncytial virus, and 1·9 days (95% CI 1·4–2·4) for rhinovirus. When using the incubation period, it is important to consider its full distribution: the right tail for quarantine policy, the central regions for likely times and sources of infection, and the full distribution for models used in pandemic planning. Our estimates combine published data to give the detail necessary for these and other applications.",,"['Lessler, Justin', 'Reich, Nicholas G', 'Brookmeyer, Ron', 'Perl, Trish M', 'Nelson, Kenrad E', 'Cummings, Derek A T']",,,,
,PMC,Identification and characterization of fully human anti-CD22 monoclonal antibodies,,PMC2726586,,,"CD22 is a member of the B cell receptor family and is implicated in B cell function and development. It is expressed on multiple forms of B cell lymphoma and is an attractive cancer therapeutic target. We report here the identification of two fully human anti-CD22 antibodies using phage display methodology. Both antibodies exhibit specific binding to cell surface-associated CD22 in multiple B cell lines. Through ELISA using mammalian cell-expressed sub-domains of CD22 as binding antigen, we mapped the binding epitopes of the newly identified CD22 antibodies to be within the Ig-like domains 5 to 7 of CD22. Their epitopes do not overlap with those of several therapeutic antibodies currently in preclinical or clinical development. These antibodies have potential as cancer therapeutic candidates and research reagents.",,"['Xiao, Xiaodong', 'Ho, Mitchell', 'Zhu, Zhongyu', 'Pastan, Ira', 'Dimitrov, Dimiter S']",,,,
,PMC,Conformational Maturation and Post-ER Multisubunit Assembly of Gap Junction Proteins,http://dx.doi.org/10.1091/mbc.E09-01-0062,PMC2675624,,,"For all previously well-characterized oligomeric integral membrane proteins, folding, multisubunit assembly, and recognition of conformationally immature molecules for degradation occurs at their organelle of synthesis. This cannot, however, be the case for the gap junction–forming protein connexin43 (Cx43), which when endogenously expressed undergoes multisubunit assembly into connexons only after its transport to the trans-Golgi network. We have developed two novel assays to assess Cx43 folding and assembly: acquisition of resistance of disulfide bonds to reduction by extracellularly added DTT and Triton X-114 detergent phase partitioning. We show that Cx43 synthesized at physiologically relevant levels undergoes a multistep conformational maturation process in which folding of connexin monomers within the ER is a prerequisite for multisubunit assembly in the TGN. Similar results were obtained with Cx32, disproving the widely reported contention that the site of endogenous β connexin assembly is the ER. Exogenous overexpression of Cx43, Cx32, or Cx26 allows these events to take place within the ER, the first example of the TGN and ER as alternative sites for oligomeric assembly. Our findings also constitute the first biochemical evidence that defective connexin folding is a cause of the human disorder X-linked Charcot-Marie-Tooth disease.",,"['VanSlyke, Judy K.', 'Naus, Christian C.', 'Musil, Linda S.']",,,,
,PMC,Developmental changes in brainstem neurons regulating lower airway caliber,http://dx.doi.org/10.1203/PDR.0b013e31819da270,PMC2761216,,,"Premature infants are at risk for lower airway obstruction; however, maturation of reflex pathways regulating lower airway patency is inadequately studied. We hypothesized that postnatal maturation causes developmental change in brainstem efferent airway-related vagal preganglionic neurons (AVPNs) within the rostral nucleus ambiguus (rNA) that project to the airways, and in pulmonary afferent fibers that terminate in the nucleus tractus solitarius (NTS). Ferrets aged 7, 14, 21 and 42 days received intrapulmonary injection of Cholera toxin β subunit (CT-b), a transganglionic retrograde tracer. Five days later, their brainstem was processed for dual immunolabeling of CT-b and the cholinergic marker, choline acetyl transferase (ChAT). CT-b labeled AVPNs and CT-b labeled afferent fiber optical density were analyzed. There was a significantly higher CT-b labeled cell number within the rNA at the youngest compared to older ages. All efferent CT-b labeled cells expressed ChAT. Optical density of CT-b labeled afferent fibers was also higher at 7 compared to 14 days. We conclude that the number of efferent AVPNs and afferent fiber optical density both diminish over the second postnatal week. We speculate that exposure to injurious agents in early postnatal life may inhibit natural remodeling and thereby enhance later vulnerability to airway hyperreactivity.",,"['Kohn, Amitai Z', 'Hoxha, Zana', 'Balan, Kannan V', 'Martin, Richard J', 'Haxhiu, Musa A', 'Wilson, Christopher G', 'Mayer, Catherine A', 'Kc, Prabha']",,,,
,PMC,Bugs and Asthma: A Different Disease?,http://dx.doi.org/10.1513/pats.200806-056RM,PMC2677401,,,"The prevalence of asthma has dramatically increased in recent decades. Exacerbations of asthma are a large contributor to asthma-related costs, and are primarily caused by viral and atypical bacterial infections. Rhinoviruses (RVs) are the most common viruses detected after an asthma exacerbation. RVs, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) viral infections early in life can induce wheezing and are associated with the development of asthma later in life. Atypical bacterial infections from Mycoplasma pneumoniae and Chlamydia pneumoniae have also been linked to chronic asthma and potential asthma exacerbations. In this article, we will discuss recent developments in viral infections, specifically RV, RSV, and hMPV, and atypical bacterial infections as causes of asthma exacerbations, including new data focusing on the host immune response in airway epithelial cells and animal models of infection.",,"['Newcomb, Dawn C.', 'Peebles, R. Stokes']",,,,
,PMC,Connection between stop codon reassignment and frequent use of shifty stop frameshifting,http://dx.doi.org/10.1261/rna.1508109,PMC2673066,,,"Ciliated protozoa of the genus Euplotes have undergone genetic code reassignment, redefining the termination codon UGA to encode cysteine. In addition, Euplotes spp. genes very frequently employ shifty stop frameshifting. Both of these phenomena involve noncanonical events at a termination codon, suggesting they might have a common cause. We recently demonstrated that Euplotes octocarinatus peptide release factor eRF1 ignores UGA termination codons while continuing to recognize UAA and UAG. Here we show that both the Tetrahymena thermophila and E. octocarinatus eRF1 factors allow efficient frameshifting at all three termination codons, suggesting that UGA redefinition also impaired UAA/UAG recognition. Mutations of the Euplotes factor restoring a phylogenetically conserved motif in eRF1 (TASNIKS) reduced programmed frameshifting at all three termination codons. Mutation of another conserved residue, Cys124, strongly reduces frameshifting at UGA while actually increasing frameshifting at UAA/UAG. We will discuss these results in light of recent biochemical characterization of these mutations.",,"['Vallabhaneni, Haritha', 'Fan-Minogue, Hua', 'Bedwell, David M.', 'Farabaugh, Philip J.']",,,,
,PMC,Agent-based modeling of host–pathogen systems: The successes and challenges,,PMC2731970,,,Agent-based models have been employed to describe numerous processes in immunology. Simulations based on these types of models have been used to enhance our understanding of immunology and disease pathology. We review various agent-based models relevant to host–pathogen systems and discuss their contributions to our understanding of biological processes. We then point out some limitations and challenges of agent-based models and encourage efforts towards reproducibility and model validation.,,"['Bauer, Amy L.', 'Beauchemin, Catherine A.A.', 'Perelson, Alan S.']",,,,
,PMC,Molecular Determinants for Subcellular Localization of the Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame 3b Protein,http://dx.doi.org/10.1128/JVI.00367-09,PMC2698541,,,"Viruses such as hepatitis C and the severe acute respiratory syndrome coronavirus (SARS-CoV) encode proteins that are distributed between mitochondria and the nucleus, but little is known about the factors that control partitioning between these sites. SARS-CoV encodes a unique accessory gene called open reading frame (ORF) 3b that, like other unique accessory genes in SARS-CoV, likely contributes to viral pathogenicity. The ORF 3b protein is 154 amino acids and is predicted to express from the second ORF in subgenomic RNA3. In this report, we have characterized the molecular components that regulate intracellular localization of the ORF 3b protein. We demonstrate unique shuttling behavior of ORF 3b, whereby the protein initially accumulates in the nucleus and subsequently translocates to mitochondria. Following nuclear localization, ORF 3b traffics to the outer membrane of mitochondria via a predicted amphipathic α-helix. Additionally, ORF 3b contains a consensus nuclear export sequence, and we demonstrate that nuclear export and thus mitochondrial translocation are dependent on a leptomycin B-sensitive nuclear export mechanism. We further show that ORF 3b inhibits induction of type I interferon induced by retinoic acid-induced gene 1 and the mitochondrial antiviral signaling protein. Our observations provide insights into the cellular localization of ORF 3b that may enhance our understanding of the mechanisms by which ORF 3b contributes to SARS-CoV pathogenesis. The findings reported here reveal that for multilocalized proteins, consideration of the spatiotemporal distribution may be crucial for understanding viral protein behavior and function.",,"['Freundt, Eric C.', 'Yu, Li', 'Park, Elizabeth', 'Lenardo, Michael J.', 'Xu, Xiao-Ning']",,,,
,PMC,The adipose renin-angiotensin system: Role in cardiovascular disease,,PMC2748818,,,"Several reviews have highlighted the importance of local tissue production of components of the renin-angiotensin system (RAS). While the concept of tissue RAS is gaining more widespread acceptance, the concept of local angiotensin II (AngII) production, acting in coordinate or independently of the endocrine RAS, continues to be debated. The primary reasons that local AngII production has been studied by many investigators are that components of the RAS are expressed by multiple cell types, and that the endocrine RAS cannot fully explain all effects of AngII. Moreover, through the development and study of genetically altered models for over-expression or knockdown of individual RAS components within specific cell types, it is becoming increasingly more evident that local RAS contribute to effects of AngII in normal physiology and disease. The purpose of this review is to define the presence and physiological significance of a local RAS in adipose tissue in relation to cardiovascular disease.",,"['Thatcher, Sean', 'Yiannikouris, Frederique', 'Gupte, Manisha', 'Cassis, Lisa']",,,,
,PMC,"Expression, crystallization and preliminary crystallographic study of human coronavirus HKU1 nonstructural protein 9",http://dx.doi.org/10.1107/S1744309109014055,PMC2675602,,,"Human coronavirus HKU1 (HCoV-HKU1) belongs to coronavirus group II and encodes 16 nonstructural proteins (nsps) which mediate genome replication and transcription. Among these nsps, nsp9 has been shown to possess single-stranded DNA/RNA-binding properties. The gene that encodes HCoV-HKU1 nsp9 was cloned and expressed in Escherichia coli and the protein was subjected to crystallization trials. The crystals diffracted to 2.7 Å resolution and belonged to space group P2(1)2(1)2, with unit-cell parameters a = 83.5, b = 88.4, c = 31.2 Å, α = β = γ = 90° and two molecules per asymmetric unit.",,"['Wang, Wei', 'Wei, Lei', 'Yang, Anqi', 'He, Teng', 'Yuen, K. Y.', 'Chen, Cheng', 'Rao, Zihe']",,,,
,PMC,Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved post-ischaemic recovery of heart contractile function,http://dx.doi.org/10.1093/cvr/cvp134,PMC2701722,,,"AIMS: This study examined the functional role of B-type natriuretic peptide (BNP) in epoxyeicosatrienoic acid (EET)-mediated cardioprotection in mice with targeted disruption of the sEH or Ephx2 gene (sEH null). METHODS AND RESULTS: Isolated mouse hearts were perfused in the Langendorff mode and subjected to global no-flow ischaemia followed by reperfusion. Hearts were analysed for recovery of left ventricular developed pressure (LVDP), mRNA levels, and protein expression. Naïve hearts from sEH null mice had similar expression of preproBNP (Nppb) mRNA compared with wild-type (WT) hearts. However, significant increases in Nppb mRNA and BNP protein expression occurred during post-ischaemic reperfusion and correlated with improved post-ischaemic recovery of LVDP. Perfusion with the putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic acid prior to ischaemia reduced the preproBNP mRNA in sEH null hearts. Inhibitor studies demonstrated that perfusion with the natriuretic peptide receptor type-A (NPR-A) antagonist, A71915, limited the improved recovery in recombinant full-length mouse BNP (rBNP)- and 11,12-EET-perfused hearts as well as in sEH null mice. Increased expression of phosphorylated protein kinase C ε and Akt were found in WT hearts perfused with either 11,12-EET or rBNP, while mitochondrial glycogen synthase kinase-3β was significantly lower in the same samples. Furthermore, treatment with the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin abolished improved LVDP recovery in 11,12-EET-treated hearts but not did significantly inhibit recovery of rBNP-treated hearts. CONCLUSION: Taken together, these data indicate that EET-mediated cardioprotection involves BNP and PI3K signalling events.",,"['Chaudhary, Ketul R.', 'Batchu, Sri Nagarjun', 'Das, Dipankar', 'Suresh, Mavanur R.', 'Falck, John R.', 'Graves, Joan P.', 'Zeldin, Darryl C.', 'Seubert, John M.']",,,,
,PMC,Swine flu outbreak tests Canadian preparedness,http://dx.doi.org/10.1503/cmaj.090805,PMC2691421,,,,,"Silversides, Ann",,,,
,PMC,α(5)β(1)-Integrin controls ebolavirus entry by regulating endosomal cathepsins,http://dx.doi.org/10.1073/pnas.0807578106,PMC2683081,,,"Integrins are involved in the binding and internalization of both enveloped and nonenveloped viruses. By using 3 distinct cell systems—CHO cells lacking expression of α(5)β(1)-integrin, HeLa cells treated with siRNA to α(5)-integrin, and mouse β(1)-integrin knockout fibroblasts, we show that α(5)β(1)-integrin is required for efficient infection by pseudovirions bearing the ebolavirus glycoprotein (GP). These integrins are necessary for viral entry but not for binding or internalization. Given the need for endosomal cathepsins B and L (CatB and CatL) to prime GPs for fusion, we investigated the status of CatB and CatL in integrin-positive and integrin-negative cell lines. α(5)β(1)-Integrin-deficient cells lacked the double-chain (DC) forms of CatB and CatL, and this correlated with decreased CatL activity in integrin-negative CHO cells. These data indicate that α(5)β(1)-integrin-negative cells may be refractory to infection by GP pseudovirions because they lack the necessary priming machinery (the double-chain forms of CatB and CatL). In support of this model, we show that GP pseudovirions that have been preprimed in vitro to generate the 19-kDa form of GP overcome the requirement for α(5)β(1)-integrin for infection. These results provide further support for the requirement for endosomal cathepsins for ebolavirus infection, identify the DC forms of these cathepsins as previously unrecognized factors that contribute to cell tropism of this virus, and reveal a previously undescribed role for integrins during viral entry as regulators of endosomal cathepsins, which are required to prime the entry proteins of ebolavirus and other pathogenic viruses.",,"['Schornberg, Kathryn L.', 'Shoemaker, Charles J.', 'Dube, Derek', 'Abshire, Michelle Y.', 'Delos, Sue E.', 'Bouton, Amy H.', 'White, Judith M.']",,,,
,PMC,Viral nanoparticles associate with regions of inflammation and blood brain barrier disruption during CNS infection,http://dx.doi.org/10.1016/j.jneuroim.2009.03.015,PMC2858070,,,"Targeted treatment of inflammatory diseases of the central nervous system (CNS) remains problematic due to the complex pathogenesis of these disorders and difficulty in drug delivery. The plant virus, cow pea mosaic virus (CPMV), has recently been explored as a nanoparticle delivery system for therapeutics targeting a number of diseases including cancer and neurodegeneration. To understand the biodistribution of CPMV in the CNS, we examined CPMV uptake during infection of mice with neurotropic mouse hepatitis virus (MHV). CPMV localized mainly to the CNS endothelium in areas that contained an intact blood brain barrier. However, in inflammatory lesions containing macrophage/microglial cell infiltration and IgG, CPMV could be detected in the brain parenchyma. Furthermore, CPMV showed rapid internalization in an in vitro model of the BBB. These results suggest that CPMV particles could be used to a vehicle to deliver therapeutics to the damaged CNS during neurodegenerative and infectious diseases of the CNS.",,"['Shriver, Leah P.', 'Koudelka, Kristopher J.', 'Manchester, Marianne']",,,,
,PMC,Identification of Cellular Proteome Modifications in Response to West Nile  Virus Infection,http://dx.doi.org/10.1074/mcp.M800565-MCP200,PMC2709190,,,"Flaviviruses are positive-stranded RNA viruses that are a public health problem because of their widespread distribution and their ability to cause a variety of diseases in humans. West Nile virus is a mosquito-borne member of this genus and is the etiologic agent of West Nile encephalitis. Clinical manifestations of West Nile virus infection are diverse, and their pathogenic mechanisms depend on complex virus-cell interactions. In the present work, we used proteomics technology to analyze early Vero cell response to West Nile infection. The differential proteomes were resolved 24 h postinfection using two-dimensional DIGE followed by mass spectrometry identification. Quantitative analysis (at least 2-fold quantitative alteration, p < 0.05) revealed 127 differentially expressed proteins with 68 up-regulated proteins and 59 down-regulated proteins of which 93 were successfully identified. The implication for mammalian cellular responses to this neurotropic flavivirus infection was analyzed and made possible more comprehensive characterization of the virus-host interactions involved in pathogenesis. The present study thus provides large scale protein-related information that should be useful for understanding how the host metabolism is modified by West Nile infection and for identifying new potential targets for antiviral therapy.",,"['Pastorino, Boris', 'Boucomont-Chapeaublanc, Elodie', 'Peyrefitte, Christophe N.', 'Belghazi, Maya', 'Fusaï, Thierry', 'Rogier, Christophe', 'Tolou, Hugues J.', 'Almeras, Lionel']",,,,
,PMC,The origin and global emergence of adamantane resistant A/H3N2 influenza viruses,http://dx.doi.org/10.1016/j.virol.2009.03.026,PMC2705899,,,"Resistance to the adamantane class of antiviral drugs by human A/H3N2 influenza viruses currently exceeds 90% in the United States and multiple Asian countries. Adamantane resistance is associated with a single amino acid change (S31N) in the M2 protein, which was shown to rapidly disseminate globally in 2005 in association with a genome reassortment event. However, the exact origin of influenza A/H3N2 viruses carrying the S31N mutation has not been characterized, particularly in South-East Asia. We therefore conducted a phylogenetic analysis of the HA, NA, and M1/2 segments of viral isolates collected between 1997-2007 from temperate localities in the Northern hemisphere (New York State, United States, 492 isolates) and Southern hemisphere (New Zealand and Australia, 629 isolates) and a subtropical locality in South-East Asia (Hong Kong, 281 isolates). We find that although the S31N mutation was independently introduced at least 11 times, the vast majority of resistant viruses now circulating globally descend from a single introduction that was first detected in the summer of 2003 in Hong Kong. These resistant viruses were continually detected in Hong Kong throughout 2003-2005, acquired a novel HA through reassortment during the first part of 2005, and thereafter spread globally. The emergence and persistence of adamantane-resistant viruses in Hong Kong further supports a source-sink model of global influenza virus ecology, in which South-East Asia experiences continuous viral activity and repeatedly seeds epidemics in temperate areas.",,"['Nelson, Martha I.', 'Simonsen, Lone', 'Viboud, Cécile', 'Miller, Mark A.', 'Holmes, Edward C.']",,,,
,PMC,The nsP3 Macro Domain is Important for Sindbis Virus Replication in Neurons and Neurovirulence in Mice,http://dx.doi.org/10.1016/j.virol.2009.03.031,PMC2683903,,,"Sindbis virus (SINV), the prototype alphavirus, contains a macro domain in the highly conserved N-terminal region of nonstructural protein 3 (nsP3). However, the biological role of the macro domain is unclear. Mutations of amino acids 10 and 24 from asparagine to alanine in the ADP-ribose binding region of the macro domain impaired SINV replication and viral RNA synthesis particularly in neurons, but did not alter binding of poly(ADP-ribose). Mutation at position 10 had the greatest effect and caused nsP3 instability in neurons, decreased SINV-induced death of mature, but not immature neurons, and attenuated virulence in 2 week-old, but not 5 day-old mice. A compensatory mutation at amino acid 31 in the macro domain of nsP3, as well as reversion of mutated amino acid 10, occurred during replication of double mutant SINV in vitro and in vivo. The nsP3 macro domain is important for SINV replication and age-dependent susceptibility to encephalomyelitis.",,"['Park, Eunhye', 'Griffin, Diane E.']",,,,
,PMC,The Crystal Structures of Chikungunya and Venezuelan Equine Encephalitis Virus nsP3 Macro Domains Define a Conserved Adenosine Binding Pocket,http://dx.doi.org/10.1128/JVI.00189-09,PMC2698539,,,"Macro domains (also called “X domains”) constitute a protein module family present in all kingdoms of life, including viruses of the Coronaviridae and Togaviridae families. Crystal structures of the macro domain from the Chikungunya virus (an “Old World” alphavirus) and the Venezuelan equine encephalitis virus (a “New World” alphavirus) were determined at resolutions of 1.65 and 2.30 Å, respectively. These domains are active as adenosine di-phosphoribose 1″-phosphate phosphatases. Both the Chikungunya and the Venezuelan equine encephalitis virus macro domains are ADP-ribose binding modules, as revealed by structural and functional analysis. A single aspartic acid conserved through all macro domains is responsible for the specific binding of the adenine base. Sequence-unspecific binding to long, negatively charged polymers such as poly(ADP-ribose), DNA, and RNA is observed and attributed to positively charged patches outside of the active site pocket, as judged by mutagenesis and binding studies. The crystal structure of the Chikungunya virus macro domain with an RNA trimer shows a binding mode utilizing the same adenine-binding pocket as ADP-ribose, but avoiding the ADP-ribose 1″-phosphate phosphatase active site. This leaves the AMP binding site as the sole common feature in all macro domains.",,"['Malet, Hélène', 'Coutard, Bruno', 'Jamal, Saïd', 'Dutartre, Hélène', 'Papageorgiou, Nicolas', 'Neuvonen, Maarit', 'Ahola, Tero', 'Forrester, Naomi', 'Gould, Ernest A.', 'Lafitte, Daniel', 'Ferron, Francois', 'Lescar, Julien', 'Gorbalenya, Alexander E.', 'de Lamballerie, Xavier', 'Canard, Bruno']",,,,
,PMC,Detection of Nonstructural Protein 6 in Murine Coronavirus-Infected Cells and Analysis of the Transmembrane Topology by Using Bioinformatics and Molecular Approaches,http://dx.doi.org/10.1128/JVI.00254-09,PMC2698535,,,"Coronaviruses encode large replicase polyproteins which are proteolytically processed by viral proteases to generate mature nonstructural proteins (nsps) that form the viral replication complex. Mouse hepatitis virus (MHV) replicase products nsp3, nsp4, and nsp6 are predicted to act as membrane anchors during assembly of the viral replication complexes. We report the first antibody-mediated Western blot detection of nsp6 from MHV-infected cells. The nsp6-specific peptide antiserum detected the replicase intermediate p150 (nsp4 to nsp11) and two nsp6 products of approximately 23 and 25 kDa. Analysis of nsp6 transmembrane topology revealed six membrane-spanning segments and a conserved hydrophobic domain in the C-terminal cytosolic tail.",,"['Baliji, Surendranath', 'Cammer, Stephen A.', 'Sobral, Bruno', 'Baker, Susan C.']",,,,
,PMC,Recognition of Mannosylated Ligands and Influenza A Virus by Human SP-D: Contributions of an Extended Site and Residue 343,http://dx.doi.org/10.1021/bi8022703,PMC2720784,,,"Surfactant protein D (SP-D) plays important roles in antiviral host defense. Although SP-D shows a preference for glucose/maltose, the protein also recognizes D-mannose and a variety of mannose-rich microbial ligands. This latter preference prompted an examination of the mechanisms of mannose recognition, particularly as they relate to high-mannose viral glycans. Trimeric neck+carbohydrate recognition domains from human SP-D (hNCRD) preferred alpha1–2 linked dimannose (DM) over the branched trimannose (TM) core, alpha1–3 or alpha1–6 DM, or D-mannose. Previous studies have shown residues flanking the carbohydrate binding site can fine-tune ligand recognition. A mutant with valine at 343 (R343V) showed enhanced binding to mannan relative to wild-type and R343A. No alteration in affinity was observed for D-mannose or for alpha1–3 or alpha1–6 linked DM; however, substantially increased affinity was observed for alpha1–2DM. Both proteins showed efficient recognition of linear and branched sub-domains of high-mannose glycans on carbohydrate microarrays, and R343V showed increased binding to a subset of the oligosaccharides. Crystallographic analysis of an R343V complex with 1,2-DM showed a novel mode of binding. The disaccharide is bound to calcium by the reducing sugar ring, and a stabilizing H-bond is formed between the 2-OH of the non-reducing sugar ring and Arg349. Although hNCRDs show negligible binding to influenza A virus (IAV), R343V showed markedly enhanced viral neutralizing activity. Hydrophobic substitutions for Arg343 selectively blocked binding of a monoclonal antibody (Hyb 246-05) that inhibits IAV binding activity. Our findings demonstrate an extended ligand binding site for mannosylated ligands and the significant contribution of the 343 side chain to specific recognition of multivalent microbial ligands, including high-mannose viral glycans.",,"['Crouch, Erika', 'Hartshorn, Kevan', 'Horlacher, Tim', 'McDonald, Barbara', 'Smith, Kelly', 'Cafarella, Tanya', 'Seaton, Barbara', 'Seeberger, Peter H.', 'Head, James']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus M Protein Inhibits Type I Interferon Production by Impeding the Formation of TRAF3·TANK·TBK1/IKKϵ Complex,http://dx.doi.org/10.1074/jbc.M109.008227,PMC2713514,,,"Severe acute respiratory syndrome (SARS) coronavirus is highly pathogenic in humans and evades innate immunity at multiple levels. It has evolved various strategies to counteract the production and action of type I interferons, which mobilize the front-line defense against viral infection. In this study we demonstrate that SARS coronavirus M protein inhibits gene transcription of type I interferons. M protein potently antagonizes the activation of interferon-stimulated response element-dependent transcription by double-stranded RNA, RIG-I, MDA5, TBK1, IKKϵ, and virus-induced signaling adaptor (VISA) but has no influence on the transcriptional activity of this element when IRF3 or IRF7 is overexpressed. M protein physically associates with RIG-I, TBK1, IKKϵ, and TRAF3 and likely sequesters some of them in membrane-associated cytoplasmic compartments. Consequently, the expression of M protein prevents the formation of TRAF3·TANK·TBK1/IKKϵ complex and thereby inhibits TBK1/IKKϵ-dependent activation of IRF3/IRF7 transcription factors. Taken together, our findings reveal a new mechanism by which SARS coronavirus circumvents the production of type I interferons.",,"['Siu, Kam-Leung', 'Kok, Kin-Hang', 'Ng, Ming-Him James', 'Poon, Vincent K. M.', 'Yuen, Kwok-Yung', 'Zheng, Bo-Jian', 'Jin, Dong-Yan']",,,,
,PMC,Multicluster nosocomial outbreak of parainfluenza virus type 3 infection in a pediatric oncohematology unit: a phylogenetic study,http://dx.doi.org/10.3324/haematol.2008.003319,PMC2688575,,,"BACKGROUND: Human parainfluenza virus type 3 (hPIV-3) has been reported to cause nosocomial outbreaks of respiratory infection, in particular among hematopoietic stem cell transplantation recipients. DESIGN AND METHODS: From September 2007 through January 2008 several episodes of hPIV-3 infection were observed among young patients followed at the Oncohematology Unit (OHU) or other units of the Pediatrics Department. In 32 young patients (median age 3.5 years, range 21 days–27 years), hPIV-3 infection was diagnosed by direct fluorescent antibody staining of cells from respiratory secretions, and virus quantified by real-time RT-PCR in nasopharyngeal aspirates or bronchoalveolar lavage samples. In addition, the epidemiologic relatedness of hPIV-3 strains was investigated by sequencing two variable regions of the hemagglutinin-neuraminidase gene (nt 1–569 and nt 762–1239). RESULTS: Of the 32 hPIV-3-positive patients, 19 were hematopoietic stem cell transplantation recipients, 8 had hematologic malignancies, and 5 were immunocompetent children. Sixteen patients had upper, and 16 lower respiratory tract infection. All patients but one had high viral load in nasopharyngeal aspirates (>1.0×10(6) RNA copies/mL). One patient died from respiratory failure with a high viral load in bronchoalveolar lavage. Phylogenetic analysis showed that 16/32 strains were identical. Besides this major cluster, three other clusters were identified, each one defining a smaller outbreak. CONCLUSIONS: Phylogenetic analysis allows identification of the role of a single or multiple hPIV-3 strains in the person-to-person transmission within an outbreak occurring in clinical units.",,"['Piralla, Antonio', 'Percivalle, Elena', 'Di Cesare-Merlone, Alessandra', 'Locatelli, Franco', 'Gerna, Giuseppe']",,,,
,PMC,Roles for endocytic trafficking and phosphatidylinositol 4-kinase III alpha in hepatitis C virus replication,http://dx.doi.org/10.1073/pnas.0902693106,PMC2678598,,,"Hepatitis C virus (HCV) reorganizes cellular membranes to establish sites of replication. The required host pathways and the mechanism of cellular membrane reorganization are poorly characterized. Therefore, we interrogated a customized small interfering RNA (siRNA) library that targets 140 host membrane-trafficking genes to identify genes required for both HCV subgenomic replication and infectious virus production. We identified 7 host cofactors of viral replication, including Cdc42 and Rock2 (actin polymerization), EEA1 and Rab5A (early endosomes), Rab7L1, and PI3-kinase C2gamma and PI4-kinase IIIalpha (phospholipid metabolism). Studies of drug inhibitors indicate actin polymerization and phospholipid kinase activity are required for HCV replication. We found extensive co-localization of the HCV replicase markers NS5A and double-stranded RNA with Rab5A and partial co-localization with Rab7L1. PI4K-IIIalpha co-localized with NS5A and double-stranded RNA in addition to being present in detergent-resistant membranes containing NS5A. In a comparison of type II and type III PI4-kinases, PI4Ks were not required for HCV entry, and only PI4K-IIIalpha was required for HCV replication. Although PI4K-IIIalpha siRNAs decreased HCV replication and virus production by almost 100%, they had no effect on initial HCV RNA translation, suggesting that PI4K-IIIalpha functions at a posttranslational stage. Electron microscopy identified the presence of membranous webs, which are thought to be the site of HCV replication, in HCV-infected cells. Pretreatment with PI4K-IIIalpha siRNAs greatly reduced the accumulation of these membranous web structures in HCV-infected cells. We propose that PI4K-IIIalpha plays an essential role in membrane alterations leading to the formation of HCV replication complexes.",,"['Berger, Kristi L.', 'Cooper, Jacob D.', 'Heaton, Nicholas S.', 'Yoon, Rosa', 'Oakland, Todd E.', 'Jordan, Tristan X.', 'Mateu, Guaniri', 'Grakoui, Arash', 'Randall, Glenn']",,,,
,PMC,Applications of high-throughput genomics to antiviral research: evasion of antiviral responses and activation of inflammation during fulminant RNA virus infection,http://dx.doi.org/10.1016/j.antiviral.2009.04.004,PMC3457704,,,"Host responses can contribute to the severity of viral infection, through the failure of innate antiviral mechanisms to recognize and restrict the pathogen, the development of intense systemic inflammation leading to circulatory failure or through tissue injury resulting from overly exuberant cell-mediated immune responses. High-throughput genomics methods are now being used to identify the biochemical pathways underlying ineffective or damaging host responses in a number of acute and chronic viral infections. This article reviews recent gene-expression studies of 1918 H1N1 influenza and Ebola hemorrhagic fever in cell culture and animal models, focusing on how genomics experiments can be used to increase our understanding of the mechanisms that permit those viruses to cause rapidly overwhelming infection. Particular attention is paid to how evasion of type I IFN responses in infected cells might contribute to over-activation of inflammatory responses. Reviewing recent research and describing how future studies might be tailored to understand the relationship between the infected cell and its environment, this article discusses how the rapidly growing field of high-throughput genomics can contribute to a more complete understanding of severe, acute viral infections and identify novel targets for therapeutic intervention.",,"Kash, John C.",,,,
,PMC,Respiratory Viruses and Eosinophils: exploring the connections,http://dx.doi.org/10.1016/j.antiviral.2009.04.005,PMC2741084,,,"In this review, we consider the role played by eosinophilic leukocytes in the pathogenesis and pathophysiology of respiratory virus infection. The vast majority of the available information on this topic focuses on respiratory syncytial virus (RSV; Family Paramyxoviridae, genus Pneumovirus), an important pediatric pathogen that infects infants worldwide. There is no vaccine currently available for RSV. A formalininactivated RSV vaccine used in a trial in the 1960s elicited immunopathology in response to natural RSV infection; this has been modeled experimentally, primarily in inbred mice and cotton rats. Eosinophils are recruited to the lung tissue in response to formalin-inactivated RSV vaccine antigens in humans and in experimental models, but they may or may not be involved in promoting the severe clinical sequelae observed. Pulmonary eosinophilia elicited in response to primary RSV infection has also been explored; this response is particularly evident in the youngest human infants and in neonatal mouse models. Although pulmonary eosinophilia is nearly always perceived in a negative light, the specific role played by virus-elicited eosinophils - negative, positive or neutral bystander - remain unclear. Lastly, we consider the data that focus on the role of eosinophils in promoting virus clearance and antiviral host defense, and conclude with a recent study that explores the role of eosinophils themselves as targets of virus infection. (215 words)",,"['Rosenberg, Helene F.', 'Dyer, Kimberly D.', 'Domachowske, Joseph B.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Papain-Like Protease Ubiquitin-Like Domain and Catalytic Domain Regulate Antagonism of IRF3 and NF-κB Signaling,http://dx.doi.org/10.1128/JVI.02220-08,PMC2698564,,,"The outcome of a viral infection is regulated in part by the complex coordination of viral and host interactions that compete for the control and optimization of virus replication. Severe acute respiratory syndrome coronavirus (SARS-CoV) intimately engages and regulates the host innate immune responses during infection. Using a novel interferon (IFN) antagonism screen, we show that the SARS-CoV proteome contains several replicase, structural, and accessory proteins that antagonize the IFN pathway. In this study, we focus on the SARS-CoV papain-like protease (PLP), which engages and antagonizes the IFN induction and NF-κB signaling pathways. PLP blocks these pathways by affecting activation of the important signaling proteins in each pathway, IRF3 and NF-κB. We also show that the ubiquitin-like domain of PLP is necessary for pathway antagonism but not sufficient by itself to block these pathways regardless of the enzymatic activity of the protease. The potential mechanism of PLP antagonism and its role in pathogenesis are discussed.",,"['Frieman, Matthew', 'Ratia, Kiira', 'Johnston, Robert E.', 'Mesecar, Andrew D.', 'Baric, Ralph S.']",,,,
,PMC,mRNA Display Design of Fibronectin-based Intrabodies That Detect and Inhibit Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein,http://dx.doi.org/10.1074/jbc.M901547200,PMC2719390,,,"The nucleocapsid (N) protein of severe acute respiratory syndrome (SARS) coronavirus plays important roles in both viral replication and modulation of host cell processes. New ligands that target the N protein may thus provide tools to track the protein inside cells, detect interaction hot spots on the protein surface, and discover sites that could be used to develop new anti-SARS therapies. Using mRNA display selection and directed evolution, we designed novel antibody-like protein affinity reagents that target SARS N protein with high affinity and selectivity. Our libraries were based on an 88-residue variant of the 10th fibronectin type III domain from human fibronectin (10Fn3). This selection resulted in eight independent 10Fn3 intrabodies, two that require the N-terminal domain for binding and six that recognize the C terminus, one with K(d) = 1.7 nm. 10Fn3 intrabodies are well expressed in mammalian cells and are relocalized by N in SARS-infected cells. Seven of the selected intrabodies tested do not perturb cellular function when expressed singly in vivo and inhibit virus replication from 11- to 5900-fold when expressed in cells prior to infection. Targeting two sites on SARS-N simultaneously using two distinct 10Fn3s results in synergistic inhibition of virus replication.",,"['Liao, Hsiang-I.', 'Olson, C. Anders', 'Hwang, Seungmin', 'Deng, Hongyu', 'Wong, Elaine', 'Baric, Ralph S.', 'Roberts, Richard W.', 'Sun, Ren']",,,,
,PMC,Averting epidemics of extensively drug-resistant tuberculosis,http://dx.doi.org/10.1073/pnas.0812472106,PMC2678614,,,"Extensively drug-resistant tuberculosis (XDR TB) has been detected in most provinces of South Africa, particularly in the KwaZulu-Natal province where several hundred cases have been reported since 2004. We analyzed the transmission dynamics of XDR TB in the region using mathematical models, and observed that nosocomial transmission clusters of XDR TB may emerge into community-based epidemics under the public health conditions of many South African communities. The effective reproductive number of XDR TB in KwaZulu-Natal may be around 2. Intensified community-based case finding and therapy appears critical to curtailing transmission. In the setting of delayed disease presentation and high system demand, improved diagnostic approaches may need to be employed in community-based programs rather than exclusively at tertiary hospitals. Using branching process mathematics, we observed that early, community-based drug-susceptibility testing and effective XDR therapy could help curtail ongoing transmission and reduce the probability of XDR TB epidemics in neighboring territories.",,"['Basu, Sanjay', 'Friedland, Gerald H.', 'Medlock, Jan', 'Andrews, Jason R.', 'Shah, N. Sarita', 'Gandhi, Neel R.', 'Moll, Anthony', 'Moodley, Prashini', 'Sturm, A. Willem', 'Galvani, Alison P.']",,,,
,PMC,Inflammatory Skin Disease in K5.hTGF-β1 Transgenic Mice Is Not Dependent on the IL-23/Th17 Inflammatory Pathway,http://dx.doi.org/10.1038/jid.2009.88,PMC2885354,,,"In the presence of IL-6, transforming growth factor (TGF)-β1 induces differentiation of T helper (Th) 17 cells in mice. Interleukin (IL)-23, a heterodimeric cytokine composed of IL-23p19 and IL-12/23p40 subunits, stimulates the growth and expansion of Th17 cells, and has been implicated in psoriasis pathogenesis. To study the associations between TGF-β1, the IL-23/Th17 inflammatory pathway, and psoriasis, we investigated inflammatory skin disease in transgenic mice that constitutively overexpress human TGF-β1 in basal keratinocytes (K5.hTGF-β1 transgenic mice); these mice had previously been reported as having a psoriasis-like disease. K5.hTGF-β1 transgenic mice had high levels of TGF-β1 mRNA and protein in both skin and serum. Levels of cytokines involved in IL-23/Th17-mediated inflammation were not elevated in lesional skin compared with those in non-lesional and wild-type skin. It is noteworthy that IL-4 and IgE were markedly elevated in inflamed skin and serum, respectively, of transgenic mice. Monoclonal antibodies (mAbs) specifically directed against IL-23p19 or IL-12/23p40 had no clinical effect on established inflammatory skin disease in K5.hTGF-β1 transgenic mice, whereas the same mAbs were able to block the development of murine experimental autoimmune encephalomyelitis, an IL-23/Th17-mediated disease. In summary, the IL-23/Th17 inflammatory pathway is not responsible for the maintenance of inflammatory skin disease in K5.hTGF-β1 transgenic mice.",,"['Fitch, Erin L.', 'Rizzo, Heather L.', 'Kurtz, Stephen E.', 'Wegmann, Keith W.', 'Gao, Wei', 'Benson, Jacqueline M.', 'Hinrichs, David J.', 'Blauvelt, Andrew']",,,,
,PMC,Bovine Coronavirus Nonstructural Protein 1 (p28) Is an RNA Binding Protein That Binds Terminal Genomic cis-Replication Elements,http://dx.doi.org/10.1128/JVI.00160-09,PMC2687364,,,"Nonstructural protein 1 (nsp1), a 28-kDa protein in the bovine coronavirus (BCoV) and closely related mouse hepatitis coronavirus, is the first protein cleaved from the open reading frame 1 (ORF 1) polyprotein product of genome translation. Recently, a 30-nucleotide (nt) cis-replication stem-loop VI (SLVI) has been mapped at nt 101 to 130 within a 288-nt 5′-terminal segment of the 738-nt nsp1 cistron in a BCoV defective interfering (DI) RNA. Since a similar nsp1 coding region appears in all characterized groups 1 and 2 coronavirus DI RNAs and must be translated in cis for BCoV DI RNA replication, we hypothesized that nsp1 might regulate ORF 1 expression by binding this intra-nsp1 cistronic element. Here, we (i) establish by mutation analysis that the 72-nt intracistronic SLV immediately upstream of SLVI is also a DI RNA cis-replication signal, (ii) show by gel shift and UV-cross-linking analyses that cellular proteins of ∼60 and 100 kDa, but not viral proteins, bind SLV and SLVI, (SLV-VI) and (iii) demonstrate by gel shift analysis that nsp1 purified from Escherichia coli does not bind SLV-VI but does bind three 5′ untranslated region (UTR)- and one 3′ UTR-located cis-replication SLs. Notably, nsp1 specifically binds SLIII and its flanking sequences in the 5′ UTR with ∼2.5 μM affinity. Additionally, under conditions enabling expression of nsp1 from DI RNA-encoded subgenomic mRNA, DI RNA levels were greatly reduced, but there was only a slight transient reduction in viral RNA levels. These results together indicate that nsp1 is an RNA-binding protein that may function to regulate viral genome translation or replication but not by binding SLV-VI within its own coding region.",,"['Gustin, Kortney M.', 'Guan, Bo-Jhih', 'Dziduszko, Agnieszka', 'Brian, David A.']",,,,
,PMC,A Longitudinal Cohort Study in Calves Evaluated for Rotavirus Infections from One to 12 Months of Age by Sequential Serological Assays,http://dx.doi.org/10.1007/s00705-009-0331-y,PMC2679849,,,"Using an immunocytochemical staining assay involving six different recombinant baculoviruses with each expressing one of the major bovine rotavirus VP7 (G6, G8 and G10) and VP4 (P6[1], P7[5] and P8[11]) serotypes, we analyzed IgG antibody responses to individual proteins in archival serum samples collected from 31 calves monthly from 1 month to 12 months of age during 1974–1975 in Higley, Arizona. Seroresponses to VP7 and VP4, as determined by a 4-fold or greater antibody response, were not always elicited concurrently following infection: in some calves, (i) seroresponses to VP7 were detected earlier than to VP4 or vice versa; and (ii) a subsequent 2(nd) seroresponse was detected for VP7 or VP4 only. In addition, a second infection was more likely to be caused by different G and/or P types. Analyses of serum samples showed that the most frequent G-P combination was G8P6[1] followed by G8P7[5], G8P8[11] and G6P6[1].",,"['Cao, Dianjun', 'Igboeli, Blessing', 'Yuan, Lijuan', 'Kapikian, Albert Z.', 'Ayers, Jess L.', 'Abinanti, Francis R.', 'Hoshino, Yasutaka']",,,,
,PMC,"Taiwan, China and the WHO: of pandas and pandemics",http://dx.doi.org/10.1503/cmaj.090613,PMC2679814,,,,,"Attaran, Amir",,,,
,PMC,Biologic Vaccines: A Panacea For Infectious Diseases?,,PMC2702811,,,"The threat of new disease pandemics has spurred the development of biologic vaccines, which promise tremendous improvements in global and local health. Several lend themselves to the prevention or treatment of chronic diseases. But the uncertainties of whom to vaccinate raise the question of whether the health care system can make these promising products viable.",,"ADAMS, KATHERINE T.",,,,
,PMC,Labs form a new front against deadly pathogens,http://dx.doi.org/10.2471/BLT.09.010409,PMC2672573,,,"A new laboratory network has formed an important front in the battle to keep emerging and dangerous pathogens, originating in animals, at bay. Jane Parry reports on the laboratories that have sprung up across Asia to meet this challenge.",,,,,,
,PMC,Total sialic acid: An acute phase reactant in cats with a possible role in feline coronavirus infection,,PMC2666320,,,"The aims of this study were to validate a colorimetric method to measure total sialic acid (TSA) in feline serum and to investigate the serum concentration of TSA in clinically healthy cats seronegative (n = 9) and seropositive (n = 48) for feline coronavirus (FCoV), and in cats affected by feline infectious peritonitis (FIP, n = 28), tumors (n = 20), or inflammation (n = 16). The correlation between TSA and α(1)-acid glycoprotein (AGP) was also investigated. The method employed in this study is precise and accurate at TSA levels (in mg/L) commonly encountered in feline serum. No significant differences between seropositive (385.6 ± 192.2 mg/L) and seronegative (433.5 ± 179.0 mg/L) cats were detectable, suggesting that the simple infection by FCoVs does not influence TSA levels. Compared with seropositive controls, the concentration of TSA was higher in cats with FIP (556.7 ± 268.3 mg/L, P = 0.003), tumors (522.5 ± 294.4 mg/L, P = 0.028), and inflammation (546.8 ± 208.3 mg/L, P = 0.018). The discriminating power of TSA for FIP is moderate (area under the ROC curve = 0.65) and the likelihood ratio is higher than 3.0 only at high TSA levels. Consequently, TSA could support a diagnosis of FIP only at extremely high serum concentration (> 800 mg/L) or when the pre-test probability of FIP is high. No correlations were found between the TSA and AGP concentrations in cats with FIP, suggesting that sialylated proteins other than AGP are present. Both the antibody titre and the degree of AGP sialylation were negatively correlated with TSA levels, suggesting that increased TSA may contribute to reduce the burden of FCoVs.",,"['Rossi, Gabriele', 'Paltrinieri, Saverio']",,,,
,PMC,Multiple diagnostic tests to identify cattle with Bovine viral diarrhea virus and duration of positive test results in persistently infected cattle,,PMC2666316,,,"Several tests for Bovine viral diarrhea virus (BVDV) were applied to samples collected monthly from December 20, 2005, through November 27, 2006 (day 0 to day 342) from 12 persistently infected (PI) cattle with BVDV subtypes found in US cattle: BVDV-1a, BVDV-1b, and BVDV-2a. The samples included clotted blood for serum, nasal swabs, and fresh and formalin-fixed ear notches. The tests were as follows: titration of infectious virus in serum and nasal swabs; antigen-capture (AC) enzyme-linked immunosorbent assay (ELISA), or ACE, on serum, nasal swabs, and fresh ear notches; gel-based polymerase chain reaction (PCR) testing of serum, nasal swabs, and fresh ear notches; immunohistochemical (IHC) testing of formalin-fixed ear notches; and serologic testing for BVDV antibodies in serum. Of the 12 animals starting the study, 3 died with mucosal disease. The ACE and IHC tests on ear notches had positive results throughout the study, as did the ACE and PCR tests on serum. There was detectable virus in nasal swabs from all the cattle throughout the study except for a few samples that were toxic to cell cultures. The serum had a virus titer ≥ log(10) 1.60 in all samples from all the cattle except for 3 collections from 1 animal. Although there were several equivocal results, the PCR test most often had positive results. The BVDV antibodies were due to vaccination or exposure to heterologous strains and did not appear to interfere with any BVDV test. These findings illustrate that PI cattle may be identified by several tests, but differentiation of PI cattle from cattle with acute BVDV infection requires additional testing, especially of blood samples and nasal swabs positive on initial testing. Also, calves PI with BVDV are continual shedders of infectious virus, as shown by the infectivity of nasal swabs over the 11-mo study.",,"['Fulton, Robert W.', 'Hessman, Bill E.', 'Ridpath, Julia F.', 'Johnson, Bill J.', 'Burge, Lurinda J.', 'Kapil, Sanjay', 'Braziel, Barbara', 'Kautz, Kira', 'Reck, Amy']",,,,
,PMC,Enhancing the Ability of Experimental Autoimmune Encephalomyelitis to Serve as a More Rigorous Model of Multiple Sclerosis through Refinement of the Experimental Design,,PMC2703151,,,"Advancing the understanding of the mechanisms involved in the pathogenesis of multiple sclerosis (MS) likely will lead to new and better therapeutics. Although important information about the disease process has been obtained from research on pathologic specimens, peripheral blood lymphocytes and MRI studies, the elucidation of detailed mechanisms has progressed largely through investigations using animal models of MS. In addition, animal models serve as an important tool for the testing of putative interventions. The most commonly studied model of MS is experimental autoimmune encephalomyelitis (EAE). This model can be induced in a variety of species and by various means, but there has been concern that the model may not accurately reflect the disease process, and more importantly, it may give rise to erroneous findings when it is used to test possible therapeutics. Several reasons have been given to explain the shortcomings of this model as a useful testing platform, but one idea provides a framework for improving the value of this model, and thus, it deserves careful consideration. In particular, the idea asserts that EAE studies are inadequately designed to enable appropriate evaluation of putative therapeutics. Here we discuss problem areas within EAE study designs and provide suggestions for their improvement. This paper is principally directed at investigators new to the field of EAE, although experienced investigators may find useful suggestions herein.",,"['Emerson, Mitchell R', 'Gallagher, Ryan J', 'Marquis, Janet G', 'LeVine, Steven M']",,,,
,PMC,The Global Role of the World Health Organization,,PMC3981564,,,"The 21(st) century global health landscape requires effective global action in the face of globalization of trade, travel, information, human rights, ideas, and disease. The new global health era is more plural, comprising a number of key actors, and requiring more coordination of effort, priorities and investments. The World Health Organization (WHO) plays an essential role in the global governance of health and disease; due to its core global functions of establishing, monitoring and enforcing international norms and standards, and coordinating multiple actors toward common goals. Global health governance requires WHO leadership and effective implementation of WHO’s core global functions to ensure better effectiveness of all health actors, but achieving this global mission could be hampered by narrowing activities and budget reallocations from core global functions.",,"['Ruger, Jennifer Prah', 'Yach, Derek']",,,,
,PMC,Clathrin and Dynamin-Dependent Endocytic Pathway Regulates Muramyl Dipeptide Internalization and NOD2 Activation,http://dx.doi.org/10.4049/jimmunol.0802197,PMC2753867,,,"Muramyl dipeptide (MDP), the NOD2 agonist, induces NF-κB and MAPK activation leading to the production of anti-microbial and pro-inflammatory molecules. MDP is internalized into acidified vesicles in macrophages. However, the endocytic mechanism of MDP uptake that induces NOD2 signaling is unknown. We now report the identification of an endocytosis pathway dependent on clathrin and dynamin that mediates MDP internalization and NOD2 activation. Intracellular MDP uptake was inhibited by chlorpromazine, a drug that disrupts clathrin-dependent endocytosis, but not by compounds that block pinocytosis or cellular entry via scavenger or mannose receptors. In contrast, MDP uptake and NOD2-dependent signaling were unimpaired in macrophages deficiency in PepT1, a peptide transporter previously implicated in MDP internalization. Both chlorpromazine and knockdown of clathrin expression by RNA interference attenuated MDP-induced NF-κB and MAPK activation. Furthermore, MDP uptake and NOD2-dependent signaling were impaired by inhibition of dynamin, a GTPase required for budding of clathrin-coated vesicles from the plasma membrane. Finally, bafilomycin A, a specific inhibitor of the vacuolar proton pump, blocked MDP accumulation in acidified vesicles and cytokine responses, suggesting that vacuolar maturation is important for MDP-induced NOD2 signaling. These studies provide evidence for a clathrin- and dynamin-dependent endocytosis pathway that mediates MDP uptake and NOD2 activation.",,"['Marina-García, Noemí', 'Franchi, Luigi', 'Kim, Yun-Gi', 'Hu, Yonjun', 'Smith, David E.', 'Boons, Geert-Jan', 'Núñez, Gabriel']",,,,
,PMC,Aetiology of influenza-like illness in adults includes parainfluenzavirus type 4,http://dx.doi.org/10.1099/jmm.0.006098-0,PMC2778239,,,"Influenza viruses cause significant morbidity and mortality in adults each winter. At the same time, other respiratory viruses circulate and cause respiratory illness with influenza-like symptoms. Human respiratory syncytial virus (HRSV), human parainfluenza viruses (HPIV) and human metapneumovirus have all been associated with morbidity and mortality in adults, including nosocomial infections. This study evaluated 154 respiratory specimens collected from adults with influenza-like/acute respiratory illness (ILI) seen at the Edward Hines Jr VA Hospital, Hines, IL, USA, during two successive winters, 1998–1999 and 1999–2000. The samples were tested for ten viruses in two nested multiplex RT-PCRs. One to three respiratory viruses were detected in 68 % of the samples. As expected, influenza A virus (FLU-A) infections were most common (50 % of the samples), followed by HRSV-A (16 %). Surprisingly, HPIV-4 infections (5.8 %) were the third most prevalent. Mixed infections were also relatively common (11 %). When present, HPIV infections were approximately three times more likely to be included in a mixed infection than FLU-A or HRSV. Mixed infections and HPIV-4 are likely to be missed using rapid diagnostic tests. This study confirms that ILI in adults and the elderly can be caused by HRSV and HPIVs, including HPIV-4, which co-circulate with FLU-A.",,"['Hasman, Hatice', 'Pachucki, Constance T.', 'Unal, Arife', 'Nguyen, Diep', 'Devlin, Troy', 'Peeples, Mark E.', 'Kwilas, Steven A.']",,,,
,PMC,"Interleukin-12 (IL-12), but Not IL-23, Deficiency Ameliorates Viral Encephalitis without Affecting Viral Control",http://dx.doi.org/10.1128/JVI.00315-09,PMC2687402,,,"The relative contributions of interleukin-12 (IL-12) and IL-23 to viral pathogenesis have not been extensively studied. IL-12p40 mRNA rapidly increases after neurotropic coronavirus infection. Infection of mice defective in both IL-12 and IL-23 (p40(−/−)), in IL-12 alone (p35(−/−)), and in IL-23 alone (p19(−/−)) revealed that the symptoms of coronavirus-induced encephalitis are regulated by IL-12. IL-17-producing cells never exceeded background levels, supporting a redundant role of IL-23 in pathogenesis. Viral control, tropism, and demyelination were all similar in p35(−/−), p19(−/−), and wild-type mice. Reduced morbidity in infected IL-12 deficient mice was also not associated with altered recruitment or composition of inflammatory cells. However, gamma interferon (IFN-γ) levels and virus-specific IFN-γ-secreting CD4 and CD8 T cells were all reduced in the central nervous systems (CNS) of infected p35(−/−) mice. Transcription of the proinflammatory cytokines IL-1β and IL-6, but not tumor necrosis factor, were initially reduced in infected p35(−/−) mice but increased to wild-type levels during peak inflammation. Furthermore, although transforming growth factor β mRNA was not affected, IL-10 was increased in the CNS in the absence of IL-12. These data suggest that IL-12 does not contribute to antiviral function within the CNS but enhances morbidity associated with viral encephalitis by increasing the ratio of IFN-γ to protective IL-10.",,"['Kapil, Parul', 'Atkinson, Roscoe', 'Ramakrishna, Chandran', 'Cua, Daniel J.', 'Bergmann, Cornelia C.', 'Stohlman, Stephen A.']",,,,
,PMC,JNK and p38 Mitogen-Activated Protein Kinase Pathways Contribute to Porcine Circovirus Type 2 Infection,http://dx.doi.org/10.1128/JVI.00135-09,PMC2687389,,,"Infection with a wide variety of viruses often perturbs host cell signaling pathways including the Jun NH(2)-terminal kinase/stress-activated kinase (JNK/SAPK) and the p38 mitogen-activated protein kinase (p38/MAPK), which are important components of cellular signal transduction pathways. The present study demonstrated for the first time that porcine circovirus type 2 (PCV2), which is the primary causative agent of an emerging swine disease, postweaning multisystemic wasting syndrome, can activate JNK1/2 and p38 MAPK pathways in PCV2-infected PK15 cells. However, PCV2 at an early stage of infection, as well as UV-irradiated PCV2, failed to activate these two MAPK families, which demonstrated that PCV2 replication was necessary for their activation. We further found that PCV2 activated the phosphorylation of JNK1/2 and p38 MAPK downstream targets c-Jun and ATF-2 with virus replication in the cultured cells. The roles of these kinases in PCV2 infection were further evaluated using specific inhibitors: the JNK inhibitor 1 for JNK1/2 and SB202190 for p38. Inhibition of JNK1/2 and p38 kinases by these specific inhibitors did result in significant reduction of PCV2 viral mRNA transcription and protein synthesis, viral progeny release, and blockage of PCV2-induced apoptotic caspase-3 activation in the infected cells. Taken together, these data suggest that JNK/SAPK and p38 MAPK pathways play important roles in the PCV2 replication and contribute to virus-mediated changes in host cells.",,"['Wei, Li', 'Zhu, Zhongwu', 'Wang, Jing', 'Liu, Jue']",,,,
,PMC,Brome mosaic virus capsid protein regulates accumulation of viral replication proteins by binding to the replicase assembly RNA element,http://dx.doi.org/10.1261/rna.1375509,PMC2661835,,,"Viruses provide valuable insights into the regulation of molecular processes. Brome mosaic virus (BMV) is one of the simplest entities with four viral proteins and three genomic RNAs. Here we report that the BMV capsid protein (CP), which functions in RNA encapsidation and virus trafficking, also represses viral RNA replication in a concentration-dependent manner by inhibiting the accumulation of the RNA replication proteins. Expression of the replication protein 2a in trans can partially rescue BMV RNA accumulation. A mutation in the CP can decrease the repression of translation. Translation repression by the CP requires a hairpin RNA motif named the B Box that contains seven loop nucleotides (nt) within the 5′ untranslated regions (UTR) of BMV RNA1 and RNA2. Purified CP can bind directly to the B Box RNA with a K (d) of 450 nM. The secondary structure of the B Box RNA was determined to contain a highly flexible 7-nt loop using NMR spectroscopy, native gel analysis, and thermal denaturation studies. The B Box is also recognized by the BMV 1a protein to assemble the BMV replicase, suggesting that the BMV CP can act to regulate several viral infection processes.",,"['Yi, Guanghui', 'Letteney, Ester', 'Kim, Chul-Hyun', 'Kao, C. Cheng']",,,,
,PMC,Predicting structures and stabilities for H-type pseudoknots with interhelix loops,http://dx.doi.org/10.1261/rna.1429009,PMC2661829,,,"RNA pseudoknots play a critical role in RNA-related biology from the assembly of ribosome to the regulation of viral gene expression. A predictive model for pseudoknot structure and stability is essential for understanding and designing RNA structure and function. A previous statistical mechanical theory allows us to treat canonical H-type RNA pseudoknots that contain no intervening loop between the helices (see S. Cao and S.J. Chen [2006] in Nucleic Acids Research, Vol. 34; pp. 2634–2652). Biologically significant RNA pseudoknots often contain interhelix loops. Predicting the structure and stability for such more-general pseudoknots remains an unsolved problem. In the present study, we develop a predictive model for pseudoknots with interhelix loops. The model gives conformational entropy, stability, and the free-energy landscape from RNA sequences. The main features of this new model are the computation of the conformational entropy and folding free-energy base on the complete conformational ensemble and rigorous treatment for the excluded volume effects. Extensive tests for the structural predictions show overall good accuracy with average sensitivity and specificity equal to 0.91 and 0.91, respectively. The theory developed here may be a solid starting point for first-principles modeling of more complex, larger RNAs.",,"['Cao, Song', 'Chen, Shi-Jie']",,,,
,PMC,Molecular Signatures of Obstructive Sleep Apnea in Adults: A Review and Perspective,,PMC2663860,,,"The consequences of obstructive sleep apnea (OSA) are largely mediated by chronic intermittent hypoxia and sleep fragmentation. The primary molecular domains affected are sympathetic activity, oxidative stress and inflammation. Other affected domains include adipokines, adhesion molecules and molecules that respond to endoplasmic reticulum stress. Changes in molecular domains affected by OSA, assessed in blood and/or urine, can provide a molecular signature for OSA that could potentially be used diagnostically and to predict who is likely to develop different OSA-related comorbidities. High-throughput discovery strategies such as microarrays, assessing changes in gene expression in circulating blood cells, have the potential to find new candidates and pathways thereby expanding the molecular signatures for OSA. More research is needed to fully understand the pathophysiological significance of these molecular signatures and their relationship with OSA comorbidities. Many OSA subjects are obese, and obesity is an independent risk factor for many comorbidities associated with OSA. Moreover, obesity affects the same molecular pathways as OSA. Thus, a challenge to establishing a molecular signature for OSA is to separate the effects of OSA from obesity. We propose that the optimal strategy is to evaluate the temporal changes in relevant molecular pathways during sleep and, in particular, the alterations from before to after sleep when assessed in blood and/or urine. Such changes will be at least partly a consequence of chronic intermittent hypoxia and sleep fragmentation that occurs during sleep. CITATION: Arnardottir ES; Mackiewicz M; Gislason T; Teff KL; Pack AI. Molecular signatures of obstructive sleep apnea in adults: A review and perspective. SLEEP 2009;32(4):447–470.",,"['Arnardottir, Erna S.', 'Mackiewicz, Miroslaw', 'Gislason, Thorarinn', 'Teff, Karen L.', 'Pack, Allan I.']",,,,
,PMC,The Role of the Charged Residues of the GP2 Helical Regions in Ebola Entry(),,PMC3516429,,,"The glycoprotein (GP) of Ebola is the sole structural protein that forms the spikes on the viral envelope. The GP contains two subunits, GP1 and GP2, linked by a disulfide bond, which are responsible for receptor binding and membrane fusion, respectively. In this study, the full length of GP gene of Ebola Zaire species, 2028 base pairs in length, was synthesized using 38 overlapping oligonucleotides by multiple rounds of polymerase chain reaction (PCR). The synthesized GP gene was shown to be efficiently expressed in mammalian cells. Furthermore, an efficient HIV-based pseudotyping system was developed using the synthetic GP gene, providing a safe approach to dissecting the entry mechanism of Ebola viruses. Using this pseudotyping system and mutational analysis, the role of the charged residues in the GP2 helical regions was examined. It was found that substitutions of the most charged residues in the regions did not adversely affect GP expression, processing, or viral incorporation, however, most of the mutations greatly impaired the ability of GP to mediate efficient viral infection. These results demonstrate that these charged residues of GP2 play an important role in GP-mediated Ebola entry into its host cells. We propose that these charged residues are involved in forming the intermediate conformation(s) of GP in membrane fusion and Ebola entry.",,"['Jiang, Haiqing', 'Wang, Jizhen', 'Manicassamy, Balaji', 'Manicassamy, Santhakumar', 'Caffrey, Michael', 'Rong, Lijun']",,,,
,PMC,The spread of awareness and its impact on epidemic outbreaks,http://dx.doi.org/10.1073/pnas.0810762106,PMC2672559,,,"When a disease breaks out in a human population, changes in behavior in response to the outbreak can alter the progression of the infectious agent. In particular, people aware of a disease in their proximity can take measures to reduce their susceptibility. Even if no centralized information is provided about the presence of a disease, such awareness can arise through first-hand observation and word of mouth. To understand the effects this can have on the spread of a disease, we formulate and analyze a mathematical model for the spread of awareness in a host population, and then link this to an epidemiological model by having more informed hosts reduce their susceptibility. We find that, in a well-mixed population, this can result in a lower size of the outbreak, but does not affect the epidemic threshold. If, however, the behavioral response is treated as a local effect arising in the proximity of an outbreak, it can completely stop a disease from spreading, although only if the infection rate is below a threshold. We show that the impact of locally spreading awareness is amplified if the social network of potential infection events and the network over which individuals communicate overlap, especially so if the networks have a high level of clustering. These findings suggest that care needs to be taken both in the interpretation of disease parameters, as well as in the prediction of the fate of future outbreaks.",,"['Funk, Sebastian', 'Gilad, Erez', 'Watkins, Chris', 'Jansen, Vincent A. A.']",,,,
,PMC,"New developments for the design, synthesis and biological evaluation of potent SARS-CoV 3CL(pro) inhibitors",http://dx.doi.org/10.1016/j.bmcl.2009.03.118,PMC4436079,,,"A series of trifluoromethyl, benzothiazolyl or thiazolyl ketone-containing peptidic compounds as SARS-CoV 3CL protease inhibitors were developed and their potency was evaluated by in vitro protease inhibitory assays. Three candidates had encouraging results for the development of new anti-SARS compounds.",,"['Regnier, Thomas', 'Sarma, Diganta', 'Hidaka, Koushi', 'Bacha, Usman', 'Freire, Ernesto', 'Hayashi, Yoshio', 'Kiso, Yoshiaki']",,,,
,PMC,Stimulated Innate Resistance of Lung Epithelium Protects Mice Broadly against Bacteria and Fungi,http://dx.doi.org/10.1165/rcmb.2008-0260OC,PMC2809220,,,"Pneumonia is a serious problem worldwide. We recently demonstrated that innate defense mechanisms of the lung are highly inducible against pneumococcal pneumonia. To determine the breadth of protection conferred by stimulation of lung mucosal innate immunity, and to identify cells and signaling pathways activated by this treatment, mice were treated with an aerosolized bacterial lysate, then challenged with lethal doses of bacterial and fungal pathogens. Mice were highly protected against a broad array of Gram-positive, Gram-negative, and class A bioterror bacterial pathogens, and the fungal pathogen, Aspergillus fumigatus. Protection was associated with rapid pathogen killing within the lungs, and this effect was recapitulated in vitro using a respiratory epithelial cell line. Gene expression analysis of lung tissue showed marked activation of NF-κB, type I and II IFN, and antifungal Card9-Bcl10-Malt1 pathways. Cytokines were the most strongly induced genes, but the inflammatory cytokines TNF and IL-6 were not required for protection. Lung-expressed antimicrobial peptides were also highly up-regulated. Taken together, stimulated innate resistance appears to occur through the activation of multiple host defense signaling pathways in lung epithelial cells, inducing rapid pathogen killing, and conferring broad protection against virulent bacterial and fungal pathogens. Augmentation of innate antimicrobial defenses of the lungs might have therapeutic value for protection of patients with neutropenia or impaired adaptive immunity against opportunistic pneumonia, and for defense of immunocompetent subjects against a bioterror threat or epidemic respiratory infection.",,"['Evans, Scott E.', 'Scott, Brenton L.', 'Clement, Cecilia G.', 'Larson, Derek T.', 'Kontoyiannis, Dimitrios', 'Lewis, Russell E.', 'LaSala, P. Rocco', 'Pawlik, Jennifer', 'Peterson, Johnny W.', 'Chopra, Ashok K.', 'Klimpel, Gary', 'Bowden, Gabriela', 'Höök, Magnus', 'Xu, Yi', 'Tuvim, Michael J.', 'Dickey, Burton F.']",,,,
,PMC,Putting Synthesis into Biology – A Viral View of Genetic Engineering Through de novo Gene and Genome synthesis,http://dx.doi.org/10.1016/j.chembiol.2009.03.002,PMC2728443,,,"The rapid improvements in DNA synthesis technology hold the potential to revolutionize biosciences in the near future. Traditional genetic engineering methods are template dependent and make extensive but laborious use of site-directed mutagenesis to explore the impact of small variations on an existing sequence “theme”. De novo gene and genome synthesis frees the investigator from the restrictions of the pre-existing template and allows for the rational design of any conceivable new sequence theme. Viruses, being amongst the simplest replicating entities, have been at the forefront of the advancing biosciences since the dawn of molecular biology. Viral genomes, especially those of RNA viruses, are relatively short, often less than 10,000 bases long, making them amenable to whole genome synthesis with the currently available technology. For this reason viruses are once again poised to lead the way in the budding field of synthetic biology – for better or worse.",,"['Mueller, Steffen', 'Coleman, J. Robert', 'Wimmer, Eckard']",,,,
,PMC,Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites,http://dx.doi.org/10.1073/pnas.0809524106,PMC2660061,,,"The coronavirus spike protein (S) plays a key role in the early steps of viral infection, with the S1 domain responsible for receptor binding and the S2 domain mediating membrane fusion. In some cases, the S protein is proteolytically cleaved at the S1–S2 boundary. In the case of the severe acute respiratory syndrome coronavirus (SARS-CoV), it has been shown that virus entry requires the endosomal protease cathepsin L; however, it was also found that infection of SARS-CoV could be strongly induced by trypsin treatment. Overall, in terms of how cleavage might activate membrane fusion, proteolytic processing of the SARS-CoV S protein remains unclear. Here, we identify a proteolytic cleavage site within the SARS-CoV S2 domain (S2′, R797). Mutation of R797 specifically inhibited trypsin-dependent fusion in both cell–cell fusion and pseudovirion entry assays. We also introduced a furin cleavage site at both the S2′ cleavage site within S2 793-KPTKR-797 (S2′), as well as at the junction of S1 and S2. Introduction of a furin cleavage site at the S2′ position allowed trypsin-independent cell–cell fusion, which was strongly increased by the presence of a second furin cleavage site at the S1–S2 position. Taken together, these data suggest a novel priming mechanism for a viral fusion protein, with a critical proteolytic cleavage event on the SARS-CoV S protein at position 797 (S2′), acting in concert with the S1–S2 cleavage site to mediate membrane fusion and virus infectivity.",,"['Belouzard, Sandrine', 'Chu, Victor C.', 'Whittaker, Gary R.']",,,,
,PMC,Inhibition of Vaccinia Virus Replication by Two Small Interfering RNAs Targeting B1R and G7L Genes and Their Synergistic Combination with Cidofovir,http://dx.doi.org/10.1128/AAC.01626-08,PMC2687203,,,"In view of the threat of the potential use of variola virus in a terrorist attack, considerable efforts have been performed to develop new antiviral strategies against orthopoxviruses. Here we report on the use of RNA interference, either alone or in combination with cidofovir, as an approach to inhibit orthopoxvirus replication. Two selected small interfering RNAs (siRNAs), named siB1R-2 and siG7L-1, and a previously reported siRNA, i.e., siD5R-2 (which targets the viral D5R mRNA), were evaluated for antiviral activity against vaccinia virus (VACV) by plaque reduction and virus yield assays. siB1R-2 and siG7L-1, administered before or after viral infection, reduced VACV replication by more than 90%. Also, these two siRNAs decreased monkeypox virus replication by 95% at a concentration of 1 nM. siB1R-2 and siG7L-1 were demonstrated to specifically silence their corresponding transcripts, i.e., B1R and G7L mRNAs, without induction of a beta interferon response. Strong synergistic effects were observed when siB1R-2, siG7L-1, or siD5R-2 was combined with cidofovir. In addition, the antiviral activities of these three siRNAs were evaluated against VACV resistant to cidofovir and other acyclic nucleoside phosphonates. siG7L-1 and siD5R-2 remained active against four of five VACV mutants, while siB1R-2 showed activity against only one of the mutants. Our results showed that siRNAs are potent inhibitory agents in vitro, not only against wild-type VACV but also against several cidofovir-resistant VACV. Furthermore, we showed that a combined therapy using siRNA and cidofovir may be useful in the treatment of poxvirus infections.",,"['Vigne, Solenne', 'Duraffour, Sophie', 'Andrei, Graciela', 'Snoeck, Robert', 'Garin, Daniel', 'Crance, Jean-Marc']",,,,
,PMC,Twenty years of cell-penetrating peptides: from molecular mechanisms to therapeutics,http://dx.doi.org/10.1111/j.1476-5381.2009.00057.x,PMC2697800,,,"The recent discovery of new potent therapeutic molecules that do not reach the clinic due to poor delivery and low bioavailability have made of delivery a key stone in therapeutic development. Several technologies have been designed to improve cellular uptake of therapeutic molecules, including cell-penetrating peptides (CPPs). CPPs were first discovered based on the potency of several proteins to enter cells. Numerous CPPs have been described so far, which can be grouped into two major classes, the first requiring chemical linkage with the drug for cellular internalization and the second involving formation of stable, non-covalent complexes with drugs. Nowadays, CPPs constitute very promising tools for non-invasive cellular import of cargo and have been successfully applied for in vitro and in vivo delivery of therapeutic molecules varying from small chemical molecule, nucleic acids, proteins, peptides, liposomes and particles. This review will focus on the structure/function and cellular uptake mechanism of CPPs in the general context of drug delivery. We will also highlight the application of peptide carriers for the delivery of therapeutic molecules and provide an update of their clinical evaluation. This article is part of a themed section on Vector Design and Drug Delivery. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009",,"['Heitz, Frederic', 'Morris, May Catherine', 'Divita, Gilles']",,,,
,PMC,Structural Basis of Inhibition Specificities of 3C and 3C-like Proteases  by Zinc-coordinating and Peptidomimetic  Compounds,http://dx.doi.org/10.1074/jbc.M807947200,PMC2658058,,,"Human coxsackievirus (CV) belongs to the picornavirus family, which consists of over 200 medically relevant viruses. In picornavirus, a chymotrypsin-like protease (3C(pro)) is required for viral replication by processing the polyproteins, and thus it is regarded as an antiviral drug target. A 3C-like protease (3CL(pro)) also exists in human coronaviruses (CoV) such as 229E and the one causing severe acute respiratory syndrome (SARS). To combat SARS, we previously had developed peptidomimetic and zinc-coordinating inhibitors of 3CL(pro). As shown in the present study, some of these compounds were also found to be active against 3C(pro) of CV strain B3 (CVB3). Several crystal structures of 3C(pro) from CVB3 and 3CL(pro) from CoV-229E and SARS-CoV in complex with the inhibitors were solved. The zinc-coordinating inhibitor is tetrahedrally coordinated to the His(40)-Cys(147) catalytic dyad of CVB3 3C(pro). The presence of specific binding pockets for the residues of peptidomimetic inhibitors explains the binding specificity. Our results provide a structural basis for inhibitor optimization and development of potential drugs for antiviral therapies.",,"['Lee, Cheng-Chung', 'Kuo, Chih-Jung', 'Ko, Tzu-Ping', 'Hsu, Min-Feng', 'Tsui, Yao-Chen', 'Chang, Shih-Cheng', 'Yang, Syaulan', 'Chen, Shu-Jen', 'Chen, Hua-Chien', 'Hsu, Ming-Chu', 'Shih, Shin-Ru', 'Liang, Po-Huang', 'Wang, Andrew H.-J.']",,,,
,PMC,Virology in the 21st Century,http://dx.doi.org/10.1128/JVI.00151-09,PMC2681991,,,,,"['Enquist, L. W.', None]",,,,
,PMC,Differential Virological and Immunological Outcome of Severe Acute Respiratory Syndrome Coronavirus Infection in Susceptible and Resistant Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2,http://dx.doi.org/10.1128/JVI.02272-08,PMC2681954,,,"We previously reported that transgenic (Tg) mice expressing human angiotensin-converting enzyme 2 (hACE2), the receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), were highly susceptible to SARS-CoV infection, which resulted in the development of disease of various severity and even death in some lineages. In this study, we further characterized and compared the pathogeneses of SARS-CoV infection in two of the most stable Tg lineages, AC70 and AC22, representing those susceptible and resistant to the lethal SARS-CoV infection, respectively. The kinetics of virus replication and the inflammatory responses within the lungs and brains, as well as the clinical and pathological outcomes, were assessed in each lineage. In addition, we generated information on lymphocyte subsets and mitogen-mediated proliferation of splenocytes. We found that while both lineages were permissive to SARS-CoV infection, causing elevated secretion of many inflammatory mediators within the lungs and brains, viral infection appeared to be more intense in AC70 than in AC22 mice, especially in the brain. Moreover, such infection was accompanied by a more profound immune suppression in the former, as evidenced by the extensive loss of T cells, compromised responses to concanavalin A stimulation, and absence of inflammatory infiltrates within the brain. We also found that CD8(+) T cells were partially effective in attenuating the pathogenesis of SARS-CoV infection in lethality-resistant AC22 mice. Collectively, our data revealed a more intense viral infection and immunosuppression in AC70 mice than in AC22 mice, thereby providing us with an immunopathogenic basis for the fatal outcome of SARS-CoV infection in the AC70 mice.",,"['Yoshikawa, Naoko', 'Yoshikawa, Tomoki', 'Hill, Terence', 'Huang, Cheng', 'Watts, Douglas M.', 'Makino, Shinji', 'Milligan, Gregg', 'Chan, Tehsheng', 'Peters, Clarence J.', 'Tseng, Chien-Te K.']",,,,
,PMC,Aquareovirus Effects Syncytiogenesis by Using a Novel Member of the FAST Protein Family Translated from a Noncanonical Translation Start Site,http://dx.doi.org/10.1128/JVI.00171-09,PMC2681948,,,"As nonenveloped viruses, the aquareoviruses and orthoreoviruses are unusual in their ability to induce cell-cell fusion and syncytium formation. While an extraordinary family of fusion-associated small transmembrane (FAST) proteins is responsible for orthoreovirus syncytiogenesis, the basis for aquareovirus-induced syncytiogenesis is unknown. We now report that the S7 genome segment of an Atlantic salmon reovirus is polycistronic and uses a noncanonical CUG translation start codon to produce a 22-kDa integral membrane protein responsible for syncytiogenesis. The aquareovirus p22 protein represents a fourth distinct member of the FAST family with a unique repertoire and arrangement of structural motifs.",,"['Racine, Trina', 'Hurst, Tara', 'Barry, Chris', 'Shou, Jingyun', 'Kibenge, Frederick', 'Duncan, Roy']",,,,
,PMC,Biochemical Characterization of Arterivirus Nonstructural Protein 11 Reveals the Nidovirus-Wide Conservation of a Replicative Endoribonuclease,http://dx.doi.org/10.1128/JVI.00261-09,PMC2681944,,,"Nidoviruses (arteriviruses, coronaviruses, and roniviruses) are a phylogenetically compact but diverse group of positive-strand RNA viruses that includes important human and animal pathogens. Nidovirus RNA synthesis is mediated by a cytoplasmic membrane-associated replication/transcription complex that includes up to 16 viral nonstructural proteins (nsps), which carry common enzymatic activities, like the viral RNA polymerase, but also unusual and poorly understood RNA-processing functions. Of these, a conserved endoribonuclease (NendoU) is a major genetic marker that is unique to nidoviruses. NendoU activity was previously verified in vitro for the coronavirus nsp15, but not for any of its distantly related orthologs from other nidovirus lineages, like the arterivirus nsp11. Here, we show that the bacterially expressed nsp11 proteins of two arteriviruses, equine arteritis virus and porcine respiratory and reproductive syndrome virus, possess pyrimidine-specific endoribonuclease activity. RNA cleavage was independent of divalent cations in vitro and was greatly reduced by replacement of residues previously implicated in catalysis. Comparative characterization of the NendoU activity in arteriviruses and severe acute respiratory syndrome coronavirus revealed common and distinct features of their substrate requirements and reaction mechanism. Our data provide the first biochemical evidence of endoribonuclease activity associated with arterivirus nsp11 and support the conclusion that this remarkable RNA-processing enzyme, whose substrate in the infected cell remains to be identified, distinguishes nidoviruses from all other RNA viruses.",,"['Nedialkova, Danny D.', 'Ulferts, Rachel', 'van den Born, Erwin', 'Lauber, Chris', 'Gorbalenya, Alexander E.', 'Ziebuhr, John', 'Snijder, Eric J.']",,,,
,PMC,Soluble Angiotensin Converting Enzyme 2 in Human Heart Failure: Relation with Myocardial Function and Clinical Outcomes,http://dx.doi.org/10.1016/j.cardfail.2009.01.014,PMC3179261,,,"OBJECTIVE: Angiotensin converting enzyme 2 (ACE2) is an endogenous counter-regulator of the renin-angiotensin system. The relationship between soluble ACE2 (sACE2), myocardial function, and clinical outcomes in patients with chronic systolic heart failure is not well established. METHODS: We measured sACE2 activity in 113 patients with chronic systolic heart failure (left ventricular ejection fraction [LVEF] ≤ 35%, NYHA class II-IV). Comprehensive echocardiography was performed at the time of blood sampling. We prospectively examined adverse clinical events (death, cardiac transplant, and heart failure hospitalizations) over 34 ± 17 months. RESULTS: Patients who had higher sACE2 plasma activity were more likely to have a lower LVEF (Spearman’s r= −0.36, p <0.001), greater RV systolic dysfunction (r=0.33, p<0.001), higher estimated pulmonary artery systolic pressure (r=0.35, p=0.002), larger LV end diastolic diameter (r=0.23, p=0.02), and higher plasma NT-proBNP levels (r=0.35, p<0.001). sACE2 was less associated with diastolic dysfunction (r=0.19, p=0.05), and was similar between patients with ischemic and non-ischemic cardiomyopathies. There was no relationship between sACE2 activity and markers of systemic inflammation. After adjusting for NT-proBNP and LVEF, sACE2 activity remained an independent predictor of adverse clinical events (HR=1.7 [95% CI: 1.1 – 2.6], p=0.018). CONCLUSIONS: Elevated plasma sACE2 activity was associated with greater severity of myocardial dysfunction and was an independent predictor of adverse clinical events.",,"['Epelman, Slava', 'Shrestha, Kevin', 'Troughton, Richard W.', 'Francis, Gary S.', 'Sen, Subha', 'Klein, Allan L.', 'Tang, W .H. Wilson']",,,,
,PMC,Yersinia pestis Can Reside in Autophagosomes and Avoid Xenophagy in Murine Macrophages by Preventing Vacuole Acidification,http://dx.doi.org/10.1128/IAI.00068-09,PMC2687347,,,"Yersinia pestis survives and replicates in phagosomes of murine macrophages. Previous studies demonstrated that Y. pestis-containing vacuoles (YCVs) acquire markers of late endosomes or lysosomes in naïve macrophages and that this bacterium can survive in macrophages activated with the cytokine gamma interferon. An autophagic process known as xenophagy, which destroys pathogens in acidic autophagolysosomes, can occur in naïve macrophages and is upregulated in activated macrophages. Studies were undertaken here to investigate the mechanism of Y. pestis survival in phagosomes of naïve and activated macrophages and to determine if the pathogen avoids or co-opts autophagy. Colocalization of the YCV with markers of autophagosomes or acidic lysosomes and the pH of the YCV were determined by microscopic imaging of infected macrophages. Some YCVs contained double membranes characteristic of autophagosomes, as determined by electron microscopy. Fluorescence microscopy showed that ∼40% of YCVs colocalized with green fluorescent protein (GFP)-LC3, a marker of autophagic membranes, and that YCVs failed to acidify below pH 7 in naïve macrophages. Replication of Y. pestis in naïve macrophages caused accumulation of LC3-II, as determined by immunoblotting. While activation of infected macrophages increased LC3-II accumulation, it decreased the percentage of GFP-LC3-positive YCVs (∼30%). A viable count assay showed that Y. pestis survived equally well in macrophages proficient for autophagy and macrophages rendered deficient for this process by Cre-mediated deletion of ATG5, revealing that this pathogen does not require autophagy for intracellular replication. We conclude that although YCVs can acquire an autophagic membrane and accumulate LC3-II, the pathogen avoids xenophagy by preventing vacuole acidification.",,"['Pujol, Céline', 'Klein, Kathryn A.', 'Romanov, Galina A.', 'Palmer, Lance E.', 'Cirota, Carol', 'Zhao, Zijiang', 'Bliska, James B.']",,,,
,PMC,Transmission of Influenza Virus via Aerosols and Fomites in the Guinea Pig Model,,PMC4180291,,,"Limited data on the relative contributions of different routes of transmission for influenza virus are available. Person-to-person transmission is central to seasonal and pandemic spread; nevertheless, the modes of spread are a matter of ongoing debate. Resolution of this discussion is paramount to the development of effective control measures in health care and community settings. Using the guinea pig model, we demonstrated that transmission of influenza A/Panama/2007/1999 (H3N2) virus through the air is efficient, compared with spread through contaminated environmental surfaces (fomites). We also examined the aerosol transmission efficiencies of 2 human influenza virus A strains and found that A/Panama/2007/1999 influenza virus transmitted more efficiently than A/Texas/36/1991 (H1N1) virus in our model. The data provide new and much-needed insights into the modes of influenza virus spread and strain-specific differences in the efficiency of transmission.",,"['Mubareka, Samira', 'Lowen, Anice C.', 'Steel, John', 'Coates, Allan L.', 'García-Sastre, Adolfo', 'Palese, Peter']",,,,
,PMC,Murine Norovirus-1 entry into permissive macrophages and dendritic cells is pH-independent,http://dx.doi.org/10.1016/j.virusres.2009.03.002,PMC2687405,,,"Murine norovirus (MNV) is a recently discovered mouse pathogen. Unlike the fastidious human noroviruses that cause the overwhelming majority of non-bacterial gastroenteritis worldwide, MNV readily infects cells in culture. Its replication in primary murine macrophages and dendritic cells and their derived cell lines allows the study of norovirus cell entry for the first time. In this study we determined the role of pH during MNV-1 infection since the low pH environment of endosomes often triggers uncoating of viruses. We demonstrated that MNV-1 viral titers by plaque assay and expression of the non-structural protein VPg by immunofluorescence were not affected by pH in cultured and primary macrophages and dendritic cells in the presence of two known endosome acidification inhibitors, bafilomycin A1 and chloroquine. These data indicate that MNV-1 enters permissive cells in a pH-independent manner.",,"['Perry, Jeffrey W.', 'Taube, Stefan', 'Wobus, Christiane E.']",,,,
,PMC,"In vivo Biodistribution of a Highly Attenuated Recombinant Vesicular Stomatitis Virus Expressing HIV-1 Gag Following Intramuscular, Intranasal, or Intravenous Inoculation",http://dx.doi.org/10.1016/j.vaccine.2009.03.006,PMC2747378,,,"Recombinant vesicular stomatitis viruses (rVSVs) are being developed as potential HIV-1 vaccine candidates. To characterize the in vivo replication and dissemination of rVSV vectors in mice, high doses of a highly attenuated vector expressing HIV-1 Gag, rVSV(IN)- N4CT9-Gag1, and a prototypic reference virus, rVSV(IN)-HIVGag5, were delivered intramuscularly (IM), intranasally (IN), or intravenously (IV). We used quantitative, real-time RT-PCR (Q-PCR) and standard plaque assays to measure the temporal dissemination of these viruses to various tissues. Following IM inoculation, both viruses were detected primarily at the injection site as well as in draining lymph nodes; neither virus induced significant weight loss, pathologic signs, or evidence of neuroinvasion. In contrast, following IN inoculation, the prototypic virus was detected in all tissues tested and caused significant weight loss leading to death. IN administration of rVSV(IN)- N4CT9-Gag1 resulted in detection in numerous tissues (brain, lung, nasal turbinates, and lymph nodes) albeit in significantly reduced levels, which caused little or no weight loss nor any mortality. Following IV inoculation, both prototypic and attenuated viruses were detected by Q-PCR in all tissues tested. In contrast to the prototype, rVSV(IN)-N4CT9-Gag1 viral loads were significantly lower in all organs tested, and no infectious virus was detected in the brain following IV inoculation, despite the presence of viral RNA. These studies demonstrated significant differences in the biodistribution patterns of and the associated pathogenicity engendered by the prototypic and attenuated vectors in a highly susceptible host.",,"['Johnson, J. Erik', 'Coleman, John W.', 'Kalyan, Narender K.', 'Calderon, Priscilla', 'Wright, Kevin J.', 'Obregon, Jennifer', 'Ogin-Wilson, Eleanor', 'Natuk, Robert J.', 'Clarke, David K.', 'Udem, Stephen A.', 'Cooper, David', 'Hendry, R. Michael']",,,,
,PMC,Akt-Mediated Transactivation of the S1P(1) Receptor in Caveolin-Enriched Microdomains Regulates Endothelial Barrier Enhancement by Oxidized Phospholipids,http://dx.doi.org/10.1161/CIRCRESAHA.108.193367,PMC3163385,,,"Endothelial cell (EC) barrier dysfunction results in increased vascular permeability, leading to increased mass transport across the vessel wall and leukocyte extravasation, the key mechanisms in pathogenesis of tissue inflammation and edema. We have previously demonstrated that OxPAPC (oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine) significantly enhances vascular endothelial barrier properties in vitro and in vivo and attenuates endothelial hyperpermeability induced by inflammatory and edemagenic agents via Rac and Cdc42 GTPase dependent mechanisms. These findings suggested potential important therapeutic value of barrier-protective oxidized phospholipids. In this study, we examined involvement of signaling complexes associated with caveolin-enriched microdomains (CEMs) in barrier-protective responses of human pulmonary ECs to OxPAPC. Immunoblotting from OxPAPC-treated ECs revealed OxPAPC-mediated rapid recruitment (5 minutes) to CEMs of the sphingosine 1-phosphate receptor (S1P(1)), the serine/threonine kinase Akt, and the Rac1 guanine nucleotide exchange factor Tiam1 and phosphorylation of caveolin-1, indicative of signaling activation in CEMs. Abolishing CEM formation (methyl-β-cyclodextrin) blocked OxPAPC-mediated Rac1 activation, cytoskeletal reorganization, and EC barrier enhancement. Silencing (small interfering RNA) Akt expression blocked OxPAPC-mediated S1P(1) activation (threonine phosphorylation), whereas silencing S1P(1) receptor expression blocked OxPAPC-mediated Tiam1 recruitment to CEMs, Rac1 activation, and EC barrier enhancement. To confirm our in vitro results in an in vivo murine model of acute lung injury with pulmonary vascular hyperpermeability, we observed that selective lung silencing of caveolin-1 or S1P(1) receptor expression blocked OxPAPC-mediated protection from ventilator-induced lung injury. Taken together, these results suggest Akt-dependent transactivation of S1P(1) within CEMs is important for OxPAPC-mediated cortical actin rearrangement and EC barrier protection.",,"['Singleton, Patrick A.', 'Chatchavalvanich, Santipongse', 'Fu, Panfeng', 'Xing, Junjie', 'Birukova, Anna A.', 'Fortune, Jennifer A.', 'Klibanov, Alexander M.', 'Garcia, Joe G. N.', 'Birukov, Konstantin G.']",,,,
,PMC,Early detection of disease outbreaks using the Internet,http://dx.doi.org/10.1503/cmaj.090215,PMC2665960,,,,,"['Wilson, Kumanan', 'Brownstein, John S.']",,,,
,PMC,ANTIVIRAL ACTIVITY OF GENETICIN AGAINST DENGUE VIRUS,http://dx.doi.org/10.1016/j.antiviral.2009.02.20,PMC2694137,,,"The aminoglycoside, geneticin (G418), was recently shown to have antiviral activity against bovine viral diarrhea virus (BVDV). Since BVDV, dengue virus (DENV) and yellow fever virus (YFV) all belong to the Flaviviridae family, it seemed possible that a common step in their life cycle might be affected by this aminoglycoside. Here it is shown that geneticin prevented the cytopathic effect (CPE) resulting from DENV-2 infection of BHK cells, in a dose-dependent manner with an EC(50) value of 3±0.4 μg/ml. Geneticin had no detectable effect on CPE caused byYFV in BHK cells. Geneticin also inhibited DENV-2 viral yield with an EC(50) value of 2±0.1 μg/ml and an EC(90) value of 20±2 μg/ml. With a CC(50) value of 165±5 μg/ml, the selectivity indexof anti-DENV activity of geneticin in BHK cells was established to be 66. Furthermore, 25 μg/ml of geneticin nearly completely blocked plaque formation induced by DENV-2, but not YFV. In addition, geneticin, inhibited DENV-2 viral RNA replication and viral translation. Gentamicin, kanamycin, and the guanidinylated geneticin showed no anti-DENV activity. Neomycin and Paromomycin demonstrated weak antiviral activity at high concentrations. Finally, aminoglycoside-3′-phosphotransferase activity of neomycin-resistant gene abolished antiviral activity of geneticin.",,"['Zhang, Xianchao G.', 'Mason, Peter W.', 'Dubovi, Edward J.', 'Xu, Xiaodong', 'Bourne, Nigel', 'Renshaw, Randall W.', 'Block, Timothy M.', 'Birk, Alexander V.']",,,,
,PMC,Optimizing comparative genomic hybridization probes for genotyping and SNP detection in Plasmodium falciparum,http://dx.doi.org/10.1016/j.ygeno.2009.02.007,PMC3095972,,,"Microarray-based comparative genomic hybridizations (CGH) interrogate genomic DNA to identify structural differences such as amplifications and deletions that are easily detected as large signal aberrations. Subtle signal deviations caused by single nucleotide polymorphisms (SNPs) can also be detected but is challenged by a high AT content (81%) in P. falciparum. We compared genome-wide CGH signal to sequence polymorphisms between parasite strains 3D7, HB3, and Dd2 using NimbleGen microarrays. From 23,191 SNPs (excluding var/rif/stevor genes), our CGH probe set detected SNPs with > 99.9% specificity but low (< 10%) sensitivity. Probe length, melting temperature, GC content, SNP location in the probe, mutation type, and hairpin structures affected SNP sensitivity. Previously unrecognized variable number tandem repeats (VNTRs) also were detected by this method. These findings will guide the redesign of a probe set to optimize an openly available CGH microarray platform for high resolution genotyping suitable for population genomics studies.",,"['Tan, John C.', 'Patel, Jigar J.', 'Tan, Asako', 'Blain, J. Craig', 'Albert, Tom J.', 'Lobo, Neil F.', 'Ferdig, Michael T.']",,,,
,PMC,Universal Detection and Identification of Avian Influenza Virus by Use of Resequencing Microarrays,http://dx.doi.org/10.1128/JCM.01346-08,PMC2668298,,,"Zoonotic microbes have historically been, and continue to emerge as, threats to human health. The recent outbreaks of highly pathogenic avian influenza virus in bird populations and the appearance of some human infections have increased the concern of a possible new influenza pandemic, which highlights the need for broad-spectrum detection methods for rapidly identifying the spread or outbreak of all variants of avian influenza virus. In this study, we demonstrate that high-density resequencing pathogen microarrays (RPM) can be such a tool. The results from 37 influenza virus isolates show that the RPM platform is an effective means for detecting and subtyping influenza virus, while simultaneously providing sequence information for strain resolution, pathogenicity, and drug resistance without additional analysis. This study establishes that the RPM platform is a broad-spectrum pathogen detection and surveillance tool for monitoring the circulation of prevalent influenza viruses in the poultry industry and in wild birds or incidental exposures and infections in humans.",,"['Lin, Baochuan', 'Malanoski, Anthony P.', 'Wang, Zheng', 'Blaney, Kate M.', 'Long, Nina C.', 'Meador, Carolyn E.', 'Metzgar, David', 'Myers, Christopher A.', 'Yingst, Samuel L.', 'Monteville, Marshall R.', 'Saad, Magdi D.', 'Schnur, Joel M.', 'Tibbetts, Clark', 'Stenger, David A.']",,,,
,PMC,Croup,,PMC2907784,,,"INTRODUCTION: Croup is characterised by the abrupt onset, most commonly at night, of a barking cough, inspiratory stridor, hoarseness, and respiratory distress due to upper airway obstruction. It leads to signs of upper airway obstruction, and must be differentiated from acute epiglottitis, bacterial tracheitis, or an inhaled foreign body. Croup affects about 3% of children a year, usually between the ages of 6 months and 3 years, and 75% of infections are caused by parainfluenza virus. Symptoms usually resolve within 48 hours, but severe infection can, rarely, lead to pneumonia, and to respiratory failure and arrest. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in children with: mild croup; moderate to severe croup; and impending respiratory failure because of severe croup? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 43 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, corticosteroids, dexamethasone (intramuscular, oral, single-dose oral, route of administration), heliox, humidification, intermittent positive pressure breathing, L-adrenaline, nebulised adrenaline (epinephrine), nebulised budesonide, nebulised short-acting beta(2) agonists, oral decongestants, oral prednisolone, oxygen, and sedatives.",,"Johnson, David Wyatt",,,,
,PMC,Role of Ceacam1 in VEGF induced vasculogenesis of murine embryonic stem cell-derived embryoid bodies in 3D culture,http://dx.doi.org/10.1016/j.yexcr.2009.02.026,PMC2745895,,,"CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1), a type I transmembrane glycoprotein involved in cell–cell adhesion has been shown to act as an angiogenic factor for mouse and human endothelial cells. Based on the ability of CEACAM1 to initiate lumen formation in human mammary epithelial cells grown in 3D culture (Matrigel), we hypothesized that murine CEACAM1 may play a similar role in vasculogenesis. In order to test this hypothesis, murine embryonic stem (ES) cells stimulated with VEGF were differentiated into embryoid bodies (EB) for 8 days (−8–0 d) and transferred to Matrigel in the presence or absence of anti-CEACAM1 antibody for an additional 12 days (0–12 d). In the absence of anti-CEACAM1 antibody or in the presence of an isotype control antibody, the EB in Matrigel underwent extensive sprouting, generating lengthy vascular structures with well-defined lumina as demonstrated by confocal microscopy, electron microscopy, and immunohistochemical analysis. Both the length and architecture of the vascular tubes were inhibited by anti-CEACAM1 mAb CC1, a mAb that blocks the cell–cell adhesion functions of CEACAM1, thus demonstrating a critical role for this cell–cell adhesion molecule in generating and maintaining vasculogenesis. QRT–PCR analysis of the VEGF treated ES cells grown under conditions that convert them to EB revealed expression of Ceacam1 as early as −5 to −3 d reaching a maximum at day 0 at which time EBs were transferred to Matrigel, thereafter levels at first declined and then increased over time. Other markers of vasculogenesis including Pecam1, VE-Cad, and Tie-1 were not detected until day 0 when EBs were transferred to Matrigel followed by a steady increase in levels, indicating later roles in vasculogenesis. In contrast, Tie-2 and Flk-1 (VEGFR2) were detected on day five of EB formation reaching a maximum at day 0 on transfer to Matrigel, similar to Ceacam1, but after which Tie-2 declined over time, while Flk-1 increased over time. QRT–PCR analysis of the anti-CEACAM1 treated ES cells revealed a significant decrease in the expression of Ceacam1, Pecam1, Tie-1, and Flk-1, while VE-Cad and Tie-2 expression were unaffected. These results suggest that the expression and signaling of CEACAM1 may affect the expression of other factors known to play critical roles in vasculogenesis. Furthermore this 3D model of vasculogenesis in an environment of extracellular matrix may be a useful model for comparison to existing models of angiogenesis.",,"['Gu, Angel', 'Tsark, Walter', 'Holmes, Kathryn V.', 'Shively, John E.']",,,,
,PMC,Development of a Neutralization Assay for Nipah Virus Using Pseudotype Particles,http://dx.doi.org/10.1016/j.jviromet.2009.02.025,PMC2704486,,,"Nipah virus (NiV) and Hendra virus (HeV) are zoonotic paramyxoviruses capable of causing severe disease in humans and animals. These viruses require biosafety level 4 (BSL-4) containment. Like other paramyxoviruses, the plaque reduction neutralization test (PRNT) can be used to detect antibodies to the surface glycoproteins, fusion (F) and attachment (G), and PRNT titers give an indication of protective immunity. Unfortunately, for NiV and HeV, the PRNT must be performed in BSL-4 containment and takes 5–7 days to complete. Thus, we have developed a neutralization assay using VSV pseudotype particles expressing the F and G proteins of NiV (pVSV-NiV-F/G) as target antigens. This rapid assay, which can be performed at BSL-2, was evaluated using serum samples from outbreak investigations and more than 300 serum samples from an experimental NiV vaccination study in swine. The results of the neutralization assays with pVSV-NiV-F/G as antigen showed a good correlation with those of standard PRNT. Therefore, this new method has the potential to be a rapid and cost-effective diagnostic method, especially in locations that lack high containment facilities, and will provide a valuable tool for basic research and vaccine development.",,"['Tamin, Azaibi', 'Harcourt, Brian H.', 'Lo, Michael K.', 'Roth, James A.', 'Wolf, Mike C.', 'Lee, Benhur', 'Weingartl, Hana', 'Audonnet, Jean-Christophe', 'Bellini, William J.', 'Rota, Paul A.']",,,,
,PMC,Is R(0) a good predictor of final epidemic size: Foot-and-Mouth Disease in the UK,http://dx.doi.org/10.1016/j.jtbi.2009.02.019,PMC2895684,,,"One of the main uses of an epidemic model is to predict the scale of an outbreak from the first few cases. In a homogeneous and non-spatial model there is a straightforward relationship between the basic reproductive ratio, R(0), and the final epidemic size; however when there is a significant spatial component to disease spread and the population is heterogeneous predicting how the epidemic size varies with the initial source of infection is far more complex. Here we use a well-developed spatio-temporal model of the spread of foot-and-mouth disease, parameterised to match the 2001 UK outbreak, to address the relationship between the scale of the epidemic and the nature of the initially infected farm. We show that there is considerable heterogeneity in both the likelihood of a epidemic and the epidemic impact (total number of farms losing livestock to either infection or control) and that these two elements are best captured by measurements at different spatial scales. The likelihood of an epidemic can be predicted from a knowledge of the reproduction ratio of the initial farm (R(i)), whereas the epidemic impact conditional on an epidemic occurring is best predicted by averaging the second-generation reproduction ratio [Formula: see text] in a 58 km ring around the infected farm. Combining these two predictions provides a good assessment of both the local and larger-scale heterogeneities present in this complex system.",,"['Tildesley, Michael J.', 'Keeling, Matt J.']",,,,
,PMC,Thermostability of the N-Terminal RNA-Binding Domain of the SARS-CoV Nucleocapsid Protein: Experiments and Numerical Simulations,http://dx.doi.org/10.1016/j.bpj.2008.10.045,PMC2717332,,,"Differential scanning calorimetry, circular dichroism spectroscopy, nuclear magnetic resonance spectroscopy, and numerical simulations were used to study the thermostability of the N-terminal RNA-binding domain (RBD) of the SARS-CoV nucleocapsid protein. The transition temperature of the RBD in a mixing buffer, composed of glycine, sodium acetate, and sodium phosphate with 100 mM sodium chloride, at pH 6.8, determined by differential scanning calorimetry and circular dichroism, is 48.74°C. Experimental results showed that the thermal-induced unfolding-folding transition of the RBD follows a two-state model with a reversibility >90%. Using a simple Gō-like model and Langevin dynamics we have shown that, in agreement with our experiments, the folding of the RBD is two-state. Theoretical estimates of thermodynamic quantities are in reasonable agreement with the experiments. Folding and thermal unfolding pathways of the RBD also were experimentally and numerically studied in detail. It was shown that the strand β(1) from the N-terminal folds last and unfolds first, while the remaining β-strands fold/unfold cooperatively.",,"['Fang, Huey-Jen', 'Chen, Yong-Zhong', 'Li, Mai Suan', 'Wu, Ming-Chya', 'Chang, Chun-Ling', 'Chang, Chung-ke', 'Hsu, Yen-lan', 'Huang, Tai-huang', 'Chen, Hueih-Min', 'Tsong, Tian-Yow', 'Hu, Chin-Kun']",,,,
,PMC,Localized spatial clustering of HIV infections in a widely disseminated rural South African epidemic,http://dx.doi.org/10.1093/ije/dyp148,PMC2720393,,,"Background South Africa contains more than one in seven of the world's HIV-positive population. Knowledge of local variation in levels of HIV infection is important for prioritization of areas for intervention. We apply two spatial analytical techniques to investigate the micro-geographical patterns and clustering of HIV infections in a high prevalence, rural population in KwaZulu-Natal, South Africa. Methods All 12 221 participants who consented to an HIV test in a population under continuous demographical surveillance were linked to their homesteads and geo-located in a geographical information system (accuracy of <2 m). We then used a two-dimensional Gaussian kernel of radius 3 km to produce robust estimates of HIV prevalence that vary across continuous geographical space. We also applied a Kulldorff spatial scan statistic (Bernoulli model) to formally identify clusters of infections (P < 0.05). Results The results reveal considerable geographical variation in local HIV prevalence (range = 6–36%) within this relatively homogenous population and provide clear empirical evidence for the localized clustering of HIV infections. Three high-risk, overlapping spatial clusters [Relative Risk (RR) = 1.34–1.62] were identified by the Kulldorff statistic along the National Road (P ≤ 0.01), whereas three low risk clusters (RR = 0.2–0.38) were identified elsewhere in the study area (P ≤ 0.017). Conclusions The findings show the existence of several localized HIV epidemics of varying intensity that are partly contained within geographically defined communities. Despite the overall high prevalence of HIV in many rural South African settings, the results support the need for interventions that target socio-geographic spaces (communities) at greatest risk to supplement measures aimed at the general population.",,"['Tanser, Frank', 'Bärnighausen, Till', 'Cooke, Graham S', 'Newell, Marie-Louise']",,,,
,PMC,Simulating Henipavirus Multicycle Replication in a Screening Assay Leads to Identification of a Promising Candidate for Therapy,http://dx.doi.org/10.1128/JVI.00164-09,PMC2682105,,,"Nipah (NiV) and Hendra (HeV) viruses are emerging zoonotic paramyxoviruses that cause encephalitis in humans, with fatality rates of up to 75%. We designed a new high-throughput screening (HTS) assay for inhibitors of infection based on envelope glycoprotein pseudotypes. The assay simulates multicycle replication and thus identifies inhibitors that target several stages of the viral life cycle, but it still can be carried out under biosafety level 2 (BSL-2) conditions. These features permit a screen for antivirals for emerging viruses and select agents that otherwise would require BSL-4 HTS facilities. The screening of a small compound library identified several effective molecules, including the well-known compound chloroquine, as highly active inhibitors of pseudotyped virus infection. Chloroquine inhibited infection with live HeV and NiV at a concentration of 1 μM in vitro (50% inhibitory concentration, 2 μM), which is less than the plasma concentrations present in humans receiving chloroquine treatment for malaria. The mechanism for chloroquine's antiviral action likely is the inhibition of cathepsin L, a cellular enzyme that is essential for the processing of the viral fusion glycoprotein and the maturation of newly budding virions. Without this processing step, virions are not infectious. The identification of a compound that inhibits a known cellular target that is important for viral maturation but that had not previously been shown to have antiviral activity for henipaviruses highlights the validity of this new screening assay. Given the established safety profile and broad experience with chloroquine in humans, the results described here provide an option for treating individuals infected by these deadly viruses.",,"['Porotto, Matteo', 'Orefice, Gianmarco', 'Yokoyama, Christine C.', 'Mungall, Bruce A.', 'Realubit, Ronald', 'Sganga, Michael L.', 'Aljofan, Mohamad', 'Whitt, Michael', 'Glickman, Fraser', 'Moscona, Anne']",,,,
,PMC,Suppression of Host Gene Expression by nsp1 Proteins of Group 2 Bat Coronaviruses,http://dx.doi.org/10.1128/JVI.02485-08,PMC2682096,,,"nsp1 protein of severe acute respiratory syndrome coronavirus (SARS-CoV), a group 2b CoV, suppresses host gene expression by promoting host mRNA degradation and translation inhibition. The present study analyzed the activities of nsp1 proteins from the group 2 bat CoV strains Rm1, 133, and HKU9-1, belonging to groups 2b, 2c, and 2d, respectively. The host mRNA degradation and translational suppression activities of nsp1 of SARS-CoV and Rm1 nsp1 were similar and stronger than the activities of the nsp1 proteins of 133 and HKU9-1. Rm1 nsp1 expression in trans strongly inhibited the induction of type I interferon (IFN-I) and IFN-stimulated genes in cells infected with an IFN-inducing SARS-CoV mutant, while 133 and HKU9-1 nsp1 proteins had relatively moderate IFN-inhibitory activities. The results of our studies suggested a conserved function among nsp1 proteins of SARS-CoV and group 2 bat CoVs.",,"['Tohya, Yukinobu', 'Narayanan, Krishna', 'Kamitani, Wataru', 'Huang, Cheng', 'Lokugamage, Kumari', 'Makino, Shinji']",,,,
,PMC,"Autophagy, antiviral immunity, and viral countermeasures",http://dx.doi.org/10.1016/j.bbamcr.2009.02.008,PMC2739265,,,"The autophagy pathway likely evolved not only to maintain cellular and tissue homeostasis but also to protect cells against microbial attack. This conserved mechanism by which cytoplasmic cargo is delivered to the endolysosomal system is now recognized as a central player in coordinating the host response to diverse intracellular pathogens, including viruses. As an endolysosomal delivery system, autophagy functions in the transfer of viruses from the cytoplasm to the lysosome where they are degraded, in the transfer of viral nucleic acids to endosomal sensors for the activation of innate immunity, and in the transfer of endogenous viral antigens to MHC class II compartments for the activation of adaptive immunity. Viruses have, in turn, evolved different strategies to antagonize, and potentially, to exploit the host autophagic machinery. Moreover, through mechanisms not yet well understood, autophagy may dampen host innate immune and inflammatory responses to viral infection. This review highlights the roles of autophagy in antiviral immunity, viral strategies to evade autophagy, and potential negative feedback functions of autophagy in the host antiviral response.",,"['Shoji-Kawata, Sanae', 'Levine, Beth']",,,,
,PMC,Transitions in State Public Health Law: Comparative Analysis of State Public Health Law Reform Following the Turning Point Model State Public Health Act,http://dx.doi.org/10.2105/AJPH.2008.140913,PMC2661440,,,"Given the public health importance of law modernization, we undertook a comparative analysis of policy efforts in 4 states (Alaska, South Carolina, Wisconsin, and Nebraska) that have considered public health law reform based on the Turning Point Model State Public Health Act. Through national legislative tracking and state case studies, we investigated how the Turning Point Act's model legal language has been considered for incorporation into state law and analyzed key facilitating and inhibiting factors for public health law reform. Our findings provide the practice community with a research base to facilitate further law reform and inform future scholarship on the role of law as a determinant of the public's health.",,"['Meier, Benjamin Mason', 'Hodge, James G.', 'Gebbie, Kristine M.']",,,,
,PMC,The impact of requiring completion of an online infection control course on health professionals’ intentions to comply with infection control guidelines: A comparative study,,PMC2690520,,,"BACKGROUND: Ensuring good infection control practice in health care facilities is a constant concern, yet evidence shows that the compliance of health care professionals with proper procedures is lacking, despite the existence of guidelines and training programs. An online infection control module was developed to provide ready access to training. Controversy exists about whether successfully completing such a course should be mandatory or strongly encouraged for all health care professionals. The objective of the present study was to compare the perception of safety culture and intention to comply with infection control guidelines in professionals who were required by their supervisors to take the course, and those who did so voluntarily. METHODS: Survey responses on learning environment, safety climate and intention to comply with infection control guidelines in health care professionals who were required to take the course (supervisor-required group [n=143]) and those who took the same course voluntarily (voluntary group [n=105]) were compared. Because randomization was thought to be too difficult to implement in the policy context in which the study was conducted, significant differences between the two groups were taken into account in the analysis. RESULTS: Those required to take the course had a significantly better perception of the institutional safety climate (P<0.001), and had a higher reported intention to comply with infection control guidelines (P=0.040) than those who took the course voluntarily. DISCUSSION: Requiring that staff complete a 30 min interactive online infection control module increased their intention to comply with infection control guidelines compared with those who voluntarily accessed this material based on promotional material. Consideration should be given to making the successful completion of an online infection control module a requirement for all health care professionals.",,"['Yassi, Annalee', 'Bryce, Elizabeth A', 'Maultsaid, Deirdre', 'Lauscher, Helen Novak', 'Zhao, Kun']",,,,
,PMC,Factors associated with serum immunoglobulin levels in beef calves from Alberta and Saskatchewan and association between passive transfer and health outcomes,,PMC2643452,,,"Inadequate consumption of colostrum can negatively affect calf health and survival. The serum immunoglobulin G (IgG) concentrations of 935 beef calves from 152 herds in Alberta and Saskatchewan have been described, using radial immunodiffusion. The determinants and health effects of serum IgG concentrations were studied in 601 calves sampled between 2 and 8 days of age. Of these calves, 6% had failure of passive transfer and an additional 10% had marginal passive transfer. Serum IgG concentrations were lower in calves born to a heifer, as a twin, or experiencing dystocia. The odds of both calf death and treatment were increased in calves with serum IgG concentrations below 24 g/L; a threshold notably higher than the 16 g/L usually considered as providing adequate passive transfer. The finding of 1/3 of calves with serum IgG concentrations less than 24 g/L suggests that calfhood treatments and mortality could be decreased by ensuring that high risk calves consume colostrum.",,"['Waldner, Cheryl L.', 'Rosengren, Leigh B.']",,,,
,PMC,High School Intervention for Influenza Biology and Epidemics/Pandemics: Impact on Conceptual Understanding among Adolescents,http://dx.doi.org/10.1187/cbe.08-08-0048,PMC2649650,,,"Understanding real-life issues such as influenza epidemiology may be of particular interest to the development of scientific knowledge and initiation of conceptual changes about viruses and their life cycles for high school students. The goal of this research project was to foster the development of adolescents' conceptual understanding of viruses and influenza biology. Thus, the project included two components: 1) pre- and posttests to determine students' conceptions about influenza biology, epidemics/pandemics, and vaccination; and 2) design an intervention that supports conceptual change to promote improvements in influenza knowledge based on these primary conceptions. Thirty-five female students from a high school biology class participated in a series of instructional activities and pre- and posttest assessments. Results from the pretest indicated that high school students exhibit a limited understanding of concepts related to viruses. Six weeks after an intervention that promoted active learning, results from a posttest showed that conceptions about influenza are more accurately related to the provided scientific knowledge. Although adolescents have nonscientific models to explain influenza biology, we showed that a carefully designed intervention can affect students' knowledge as well as influence the implementation of health education programs in secondary schools.",,"['Dumais, Nancy', 'Hasni, Abdelkrim']",,,,
,PMC,A Crash Course in Evolution,http://dx.doi.org/10.1187/cbe.08-12-0079,PMC2649647,,,,,"Kalumuck, Karen",,,,
,PMC,Uncharted Paths*: Hospital Networks in Critical Care,http://dx.doi.org/10.1378/chest.08-1052,PMC2692049,,,"Wide variation between hospitals in the quality of critical care lead to many potentially avoidable deaths. Regionalization of critical care is a possible solution; regionalization has been implemented for trauma and neonatal intensive care, and it is under active discussion for medical and cardiac critical care. However, regionalization is only one possible approach to reorganizing critical care services. This commentary introduces the technique of network analysis as a framework for the following: (1) understanding how critically ill patients move between hospitals, (2) defining the roles hospitals play in regional care delivery, and (3) suggesting systematic improvements that may benefit population health. We examined transfers of critically ill Medicare patients in Connecticut in 2005 as a model system. We found that patients are systematically transferred to more capable hospitals. However, we find the standard distinction of hospitals into either “secondary hospitals” or “tertiary hospitals” poorly explains observed transfer patterns; instead, hospitals show a continuum of roles. We further examine the implications of the network pattern in a simulation of quarantine of a hospital to incoming transfers, as occurred during the severe acute respiratory syndrome epidemic. Network perspectives offer new ways to study systems to care for critically ill patients and provide additional tools for addressing pragmatic problems in triage and bed management, regionalization, quality improvement, and disaster preparedness.",,"['Iwashyna, Theodore J.', 'Christie, Jason D.', 'Kahn, Jeremy M.', 'Asch, David A.']",,,,
,PMC,"Behind the data: Establishing the Network for Surveillance for Pneumococcal Diseases in the East African Region, netSPEAR",http://dx.doi.org/10.1086/596496,PMC2673058,,,"In a region with high rates of mortality among children aged <5 years, the underfunded health care systems of sub-Saharan Africa have few resources available to perform surveillance activities that can help determine the causes of morbidity and mortality in the region. At present, there are few examples of attempts to promote public health care surveillance that might inform current debates about how to expand and improve surveillance, particularly for bacterial diseases. Driven by this gap in knowledge, we attempted to explore the successes and failures of the Network for Surveillance of Pneumococcal Disease in the East African Region and to share the experiences of what are essentially non research public-sector hospitals in East Africa, with the hopes that surveillance systems for other diseases, especially those that require complex diagnostic support, may be informed by these experiences. The state of services essential for surveillance and the measures taken to overcome any shortcomings are described, as is the progress made in improving clinical diagnosis, laboratory processing, and data management. For surveillance to play a role in public health care, ministries of health and associated institutions must own and push forward the surveillance agenda, with support from global partners, and take advantage of the developments that have been achieved within the institutions.",,"['Amos, Ben', 'Kisakye, Annet', 'Makewa, Douglas', 'Mudhune, Sandra', 'Mwamtemi, Hadija', 'Nansera, Dennis', 'Ngwiri, Thomas', 'Wamae, Maranga', 'English, Mike', None]",,,,
,PMC,"Potent Human Monoclonal Antibodies against SARS CoV, Nipah and Hendra Viruses",http://dx.doi.org/10.1517/14712590902763755,PMC2705284,,,"Polyclonal antibodies have a century-old history of being effective against some viruses; recently, monoclonal antibodies (mAbs) have also shown success. The humanized mAb Synagis (palivizumab) remains still the only mAb against respiratory syncytial virus (RSV) infections approved by the U.S. Food and Drug Administration (FDA). Recently, several potent human monoclonal antibodies (hmAbs) targeting the Severe Acute Respiratory Syndrome-Associated coronavirus (SARS CoV) S glycoproteins were developed quickly after the virus was identified in 2003. Among these antibodies, m396 and S230.15 exhibit exceptional potency and cross-reactivity as they neutralize isolates from the first and second outbreaks and from palm civets both in vitroand in mice. Similarly, the first fully hmAbs against two other paramyxoviruses, Hendra virus (HeV) and Nipah virus (NiV), which can cause up to 75% mortality, were recently developed; one of them, m102.4, shows exceptional cross-reactive potency against both NiV and HeV. Three-dimensional molecular structures of envelope glycoproteins from these viruses in complexes with antibodies and/or receptors were recently determined. Structural analyses along with other experiments have provided insights into the molecular mechanisms of receptor recognition and antibody neutralization, and suggested that these antibodies alone or in combination could successfully fight the viruses’ heterogeneity and mutability which is a major problem in the development of effective therapeutic agents against viruses, including therapeutic antibodies.",,"['Prabakaran, Ponraj', 'Zhongyu, Zhu', 'Xiao, Xiaodong', 'Biragyn, Arya', 'Dimitrov, Antony S.', 'Broder, Christopher C.', 'Dimitrov, Dimiter S.']",,,,
,PMC,Effects of Storage Temperature and Time on Clinical Biochemical Parameters from Rat Serum,,PMC2679668,,,"Serum is often frozen and banked for analysis at a later date. This study assessed the stability of 17 analytes in rat serum during refrigeration at 4 °C and extended storage at −20 °C (frost-free and nonfrost-free freezers) and −70 °C. Samples were analyzed by using an automated dry-slide chemistry analyzer at time 0 and then stored as aliquots for analysis at time points including day 7, 30, 90, and 360. After 7 d of refrigeration, only creatine kinase activity had varied by more than 10% of the starting value. Freezing at −70 °C was clearly superior to −20 °C where changes were observed in CO(2) as early as day 30 and alanine aminotransferase as early as day 90. Samples stored in frost-free and nonfrost-free −20 °C freezers did not differ significantly through day 90. Factors such as storage time and temperature should be considered when designing any retrospective study.",,"['Cray, Carolyn', 'Rodriguez, Marilyn', 'Zaias, Julia', 'Altman, Norman H']",,,,
,PMC,Immunotoxicity of monoclonal antibodies,,PMC2725414,,,"Monoclonal antibodies (mAbs) are large molecules intended to bind to specific targets often expressed on the immune system, and to treat various immunopathological conditions. Therefore, mAbs can be considered to have a high potential for immunotoxicity, which is reflected in the clinical experience accumulated on mAbs-induced adverse effects related to immunosuppression, immunostimulation and hypersensitivity (immunogenicity). So far, non clinical immunotoxicity studies have been inadequate to address all safety issues in relation to the possible immunotoxicity of mAbs, because they are fraught with limitations and pitfalls primarily related to the lack of relevant animal species. In addition, clinical studies rarely include validated end-points dedicated to the prediction of immunotoxicity. With the ongoing development of mAbs as novel therapeutic strategies for a wide variety of diseases, efforts should be paid to improve our understanding of mAbs-induced immunotoxic effects and design dedicated strategies to assess their immunological safety, both non clinically and clinically.",,"Descotes, Jacques",,,,
,PMC,A Gripping Tale of Ribosomal Frameshifting: Extragenic Suppressors of Frameshift Mutations Spotlight P-Site Realignment,http://dx.doi.org/10.1128/MMBR.00010-08,PMC2650885,,,"Summary: Mutants of translation components which compensate for both −1 and +1 frameshift mutations showed the first evidence for framing malleability. Those compensatory mutants isolated in bacteria and yeast with altered tRNA or protein factors are reviewed here and are considered to primarily cause altered P-site realignment and not altered translocation. Though the first sequenced tRNA mutant which suppressed a +1 frameshift mutation had an extra base in its anticodon loop and led to a textbook “yardstick” model in which the number of anticodon bases determines codon size, this model has long been discounted, although not by all. Accordingly, the reviewed data suggest that reading frame maintenance and translocation are two distinct features of the ribosome. None of the −1 tRNA suppressors have anticodon loops with fewer than the standard seven nucleotides. Many of the tRNA mutants potentially affect tRNA bending and/or stability and can be used for functional assays, and one has the conserved C74 of the 3′ CCA substituted. The effect of tRNA modification deficiencies on framing has been particularly informative. The properties of some mutants suggest the use of alternative tRNA anticodon loop stack conformations by individual tRNAs in one translation cycle. The mutant proteins range from defective release factors with delayed decoding of A-site stop codons facilitating P-site frameshifting to altered EF-Tu/EF1α to mutant ribosomal large- and small-subunit proteins L9 and S9. Their study is revealing how mRNA slippage is restrained except where it is programmed to occur and be utilized.",,"['Atkins, John F.', 'Björk, Glenn R.']",,,,
,PMC,Therapeutic Potential of Splice-Switching Oligonucleotides,http://dx.doi.org/10.1089/oli.2008.0161,PMC2663420,,,"Alternative splicing enables a single pre-messenger RNA transcript to yield multiple protein isoforms, making it a major contributor to the diversity of the proteome. While this process is essential for normal development, aberrations in alternative splicing are the cause of a multitude of human diseases. Methods for manipulating alternative splicing would thus be of therapeutic value. Chemically modified antisense oligonucleotides that alter alternative splicing by directing splice site selection have been developed to achieve this end. These splice-switching oligonucleotides (SSOs) have been applied to correct aberrant splicing, induce expression of a therapeutic splice variant, or induce expression of a novel therapeutic splice variant in a number of disease-relevant genes. Recently, in vivo efficacy of SSOs has been reported using animal disease models, as well as in results from the first clinical trial.",,"['Bauman, John', 'Jearawiriyapaisarn, Natee', 'Kole, Ryszard']",,,,
,PMC,A New Paradigm for Quarantine and Public Health Activities at Land Borders: Opportunities and Challenges,,PMC2646476,,,"The Institute of Medicine (IOM) report Quarantine Stations at Ports of Entry: Protecting the Public's Health focused almost exclusively on U.S. airports and seaports, which served 106 million entries in 2005. IOM concluded that the primary function of these quarantine stations (QSs) should shift from providing inspection to providing strategic national public health leadership. The large expanse of our national borders, large number of crossings, sparse federal resources, and decreased regulation regarding conveyances crossing these borders make land borders more permeable to a variety of threats. To address the health challenges related to land borders, the QSs serving such borders must assume unique roles and partnerships to achieve the strategic leadership and public health research roles envisioned by the IOM. In this article, we examine how the IOM recommendations apply to the QSs that serve the land borders through which more than 319 million travelers, immigrants, and refugees entered the U.S. in 2005.",,"['Waterman, Stephen H.', 'Escobedo, Miguel', 'Wilson, Todd', 'Edelson, Paul J.', 'Bethel, Jeffrey W.', 'Fishbein, Daniel B.']",,,,
,PMC,Resource Allocation on the Frontlines of Public Health Preparedness and Response: Report of a Summit on Legal and Ethical Issues,,PMC2646457,,,"OBJECTIVES: In the face of all-hazards preparedness challenges, local and state health department personnel have to date lacked a discrete set of legally and ethically informed public health principles to guide the distribution of scarce resources in crisis settings. To help address this gap, we convened a Summit of academic and practice experts to develop a set of principles for legally and ethically sound public health resource triage decision-making in emergencies. METHODS: The invitation-only Summit, held in Washington, D.C., on June 29, 2006, assembled 20 experts from a combination of academic institutions and nonacademic leadership, policy, and practice settings. The Summit featured a tabletop exercise designed to highlight resource scarcity challenges in a public health infectious disease emergency. This exercise served as a springboard for Summit participants' subsequent identification of 10 public health emergency resource allocation principles through an iterative process. RESULTS: The final product of the Summit was a set of 10 principles to guide allocation decisions involving scarce resources in public health emergencies. The principles are grouped into three categories: obligations to community; balancing personal autonomy and community well-being/benefit; and good preparedness practice. CONCLUSIONS: The 10 Summit-derived principles represent an attempt to link law, ethics, and real-world public health emergency resource allocation practices, and can serve as a useful starting framework to guide further systematic approaches and future research on addressing public health resource scarcity in an all-hazards context.",,"['Barnett, Daniel J.', 'Taylor, Holly A.', 'Hodge, James G.', 'Links, Jonathan M.']",,,,
,PMC,Use of a universal virus detection assay to identify human metapneumovirus in a hematopoietic stem cell transplant recipient with pneumonia of unknown origin,http://dx.doi.org/10.1016/j.jcv.2009.01.011,PMC2663017,,,"BACKGROUND: Development of uncommon viral infections in immunocompromised transplant recipients can pose major diagnostic challenges. We present a case report of an immunocompromised patient suffering from pneumonia, for which the causative agent was not identified by routine methods. OBJECTIVES: To identify the potential cause of the pneumonia using a degenerate oligonucleotide primer (DOP) PCR assay which is designed to detect all viruses. STUDY DESIGN: DOP-PCR was applied to bronchoalveolar lavage fluid from this patient. Generic PCR products were cloned and sequenced. RESULTS: The novel universal virus assay detected human metapneumovirus in the clinical sample. The finding was confirmed by two independent metapneumovirus specific PCRs targeting independent regions of the viral genome. CONCLUSIONS: The DOP PCR was used to detect and identify the sequence of an unidentified virus. This study provides proof of concept for the use on clinically relevant specimens of this unbiased universal assay, which requires no previous viral sequence information.",,"['Uhlenhaut, Christine', 'Cohen, Jeffrey I.', 'Fedorko, Daniel', 'Nanda, Santosh', 'Krause, Philip R.']",,,,
,PMC,Adenovirus receptors and their implications in gene delivery,http://dx.doi.org/10.1016/j.virusres.2009.02.010,PMC2903974,,,"Adenoviruses (Ads) have gained popularity as gene delivery vectors for therapeutic and prophylactic applications. Ad entry into host cells involves specific interactions between cell surface receptors and viral capsid proteins. Several cell surface molecules have been identified as receptors for Ad attachment and entry. Tissue tropism of Ad vectors is greatly influenced by their receptor usage. A variety of strategies have been investigated to modify Ad vector tropism by manipulating the receptor-interacting moieties. Many such strategies are aimed at targeting and/or detargeting of Ad vectors. In this review, we discuss the various cell surface molecules that are implicated as receptors for virus attachment and internalization. Special emphasis is given to Ad types that are utilized as gene delivery vectors. Various strategies to modify Ad tropism using the knowledge of Ad receptors are also discussed.",,"['Sharma, Anurag', 'Li, Xiaoxin', 'Bangari, Dinesh S.', 'Mittal, Suresh K.']",,,,
,PMC,Threshold parameters for a model of epidemic spread among households and workplaces,http://dx.doi.org/10.1098/rsif.2008.0493,PMC2827443,,,"The basic reproduction number R (0) is one of the most important concepts in modern infectious disease epidemiology. However, for more realistic and more complex models than those assuming homogeneous mixing in the population, other threshold quantities can be defined that are sometimes more useful and easily derived in terms of model parameters. In this paper, we present a model for the spread of a permanently immunizing infection in a population socially structured into households and workplaces/schools, and we propose and discuss a new household-to-household reproduction number R (H) for it. We show how R (H) overcomes some of the limitations of a previously proposed threshold parameter, and we highlight its relationship with the effort required to control an epidemic when interventions are targeted at randomly selected households.",,"['Pellis, L.', 'Ferguson, N. M.', 'Fraser, C.']",,,,
,PMC,"Rotavirus Antagonizes Cellular Antiviral Responses by Inhibiting the Nuclear Accumulation of STAT1, STAT2, and NF-κB",http://dx.doi.org/10.1128/JVI.01450-08,PMC2682104,,,"A vital arm of the innate immune response to viral infection is the induction and subsequent antiviral effects of interferon (IFN). Rotavirus reduces type I IFN induction in infected cells by the degradation of IFN regulatory factors. Here, we show that the monkey rotavirus RRV and human rotavirus Wa also block gene expression induced by type I and II IFNs through a mechanism allowing signal transducer and activator of transcription 1 (STAT1) and STAT2 activation but preventing their nuclear accumulation. In infected cells, this may allow rotavirus to block the antiviral actions of IFN produced early in infection or by activated immune cells. As the intracellular expression of rotavirus nonstructural proteins NSP1, NSP3, and NSP4 individually did not inhibit IFN-stimulated gene expression, their involvement in this process is unlikely. RRV and Wa rotaviruses also prevented the tumor necrosis factor alpha-stimulated nuclear accumulation of NF-κB and NF-κB-driven gene expression. In addition, NF-κB was activated by rotavirus infection, confirming earlier findings by others. As NF-κB is important for the induction of IFN and other cytokines during viral infection, this suggests that rotavirus prevents cellular transcription as a means to evade host responses. To our knowledge, this is the first report of the use of this strategy by a double-stranded RNA virus.",,"['Holloway, Gavan', 'Truong, Thanhmai T.', 'Coulson, Barbara S.']",,,,
,PMC,Ganglioside-Linked Terminal Sialic Acid Moieties on Murine Macrophages Function as Attachment Receptors for Murine Noroviruses,http://dx.doi.org/10.1128/JVI.02245-08,PMC2668497,,,"Noroviruses are the major cause of nonbacterial gastroenteritis in humans. However, little is known regarding the norovirus life cycle, including cell binding and entry. In contrast to human noroviruses, the recently discovered murine norovirus 1 (MNV-1) readily infects murine macrophages and dendritic cells in culture. Many viruses, including the related feline calicivirus, use terminal sialic acids (SA) as receptors for infection. Therefore, we tested whether SA moieties play a role during MNV-1 infection of murine macrophages. Competition with SA-binding lectins and neuraminidase treatment led to a reduction in MNV-1 binding and infection in cultured and primary murine macrophages, suggesting a role for SA during the initial steps of the MNV-1 life cycle. Because SA moieties can be attached to glycolipids (i.e., gangliosides), we next determined whether MNV-1 uses gangliosides during infection. The gangliosides GD1a, GM1, and asialo-GM1 (GA1) are natural components of murine macrophages. MNV-1 bound to ganglioside GD1a, which is characterized by an SA on the terminal galactose, but not to GM1 or asialo-GM1 in an enzyme-linked immunosorbent assay. The depletion of gangliosides using an inhibitor of glycosylceramide synthase (d-threo-P4) led to a reduction of MNV-1 binding and infection in cultured and primary murine macrophages. This defect was specifically rescued by the addition of GD1a. A similar phenotype was observed for MNV field strains WU11 (GV/WU11/2005/USA) and S99 (GV/Berlin/2006/DE). In conclusion, our data indicate that MNV can use terminal SA on gangliosides as attachment receptors during binding to murine macrophages.",,"['Taube, Stefan', 'Perry, Jeffrey W.', 'Yetming, Kristen', 'Patel, Sagar P.', 'Auble, Heather', 'Shu, Liming', 'Nawar, Hesham F.', 'Lee, Chang Hoon', 'Connell, Terry D.', 'Shayman, James A.', 'Wobus, Christiane E.']",,,,
,PMC,The Autographa californica Multicapsid Nucleopolyhedrovirus GP64 Protein: Analysis of Transmembrane Domain Length and Sequence Requirements,http://dx.doi.org/10.1128/JVI.02252-08,PMC2668483,,,"GP64, the major envelope glycoprotein of the Autographa californica multicapsid nucleopolyhedrovirus budded virion, is important for host cell receptor binding and mediates low-pH-triggered membrane fusion during entry by endocytosis. Previous transmembrane (TM) domain replacement studies showed that the TM domain serves a critical role in GP64 function. To extend the prior studies and examine specific sequence requirements of the TM domain, we generated a variety of GP64 TM domain mutations. The mutations included 4- to 8-amino-acid deletions, as well as single and multiple point mutations. While most TM domain deletion constructs remained fusion competent, those containing deletions of eight amino acids from the C terminus did not mediate detectable fusion. The addition of a hydrophobic amino acid (A, L, or V) to the C terminus of construct C8 (a construct that contains a TM domain deletion of eight amino acids from the C terminus) restored fusion activity. These data suggest that the membrane fusion function of GP64 is dependent on a critical length of the hydrophobic TM domain. All GP64 proteins with a truncated TM domain mediated detectable virion budding with dramatically lower levels of efficiency than wild-type GP64. The effects of deletions of various lengths and positions in the TM domain were also examined for their effects on viral infectivity. Further analysis of the TM domain by single amino acid substitutions and 3-alanine scanning mutations identified important but not essential amino acid positions. These studies showed that amino acids at positions 485 to 487 and 503 to 505 are important for cell surface expression of GP64, while amino acids at positions 483 to 484 and 494 to 496 are important for virus budding. Overall, our results show that specific features and amino acid sequences, particularly the length of the hydrophobic TM domain, play critical roles in membrane anchoring, membrane fusion, virus budding, and infectivity.",,"['Li, Zhaofei', 'Blissard, Gary W.']",,,,
,PMC,Contribution of Bordetella bronchiseptica Filamentous Hemagglutinin and Pertactin to Respiratory Disease in Swine,http://dx.doi.org/10.1128/IAI.01379-08,PMC2681739,,,"Bordetella bronchiseptica is pervasive in swine populations and plays multiple roles in respiratory disease. Most studies addressing virulence factors of B. bronchiseptica are based on isolates derived from hosts other than pigs. Two well-studied virulence factors implicated in the adhesion process are filamentous hemagglutinin (FHA) and pertactin (PRN). We hypothesized that both FHA and PRN would serve critical roles in the adhesion process and be necessary for colonization of the swine respiratory tract. To investigate the role of FHA and PRN in Bordetella pathogenesis in swine, we constructed mutants containing an in-frame deletion of the FHA or the PRN structural gene in a virulent B. bronchiseptica swine isolate. Both mutants were compared to the wild-type swine isolate for their ability to colonize and cause disease in swine. Colonization of the FHA mutant was lower than that of the wild type at all respiratory tract sites and time points examined and caused limited to no disease. In contrast, the PRN mutant caused similar disease severity relative to the wild type; however, colonization of the PRN mutant was reduced relative to the wild type during early and late infection and induced higher anti-Bordetella antibody titers. Together, our results indicate that despite inducing different pathologies and antibody responses, both FHA and PRN are necessary for optimal colonization of the swine respiratory tract.",,"['Nicholson, Tracy L.', 'Brockmeier, Susan L.', 'Loving, Crystal L.']",,,,
,PMC,High-throughput isolation of immunoglobulin genes from single human B cells and expression as monoclonal antibodies,http://dx.doi.org/10.1016/j.jviromet.2009.02.014,PMC2805188,,,"Defining human B cell repertoires to viral pathogens is critical for design of vaccines that induce broadly protective antibodies to infections such as HIV-1 and influenza. Single B cell sorting and cloning of immunoglobulin (Ig) heavy- and light-chain variable regions (V(H) and V(L)) is a powerful technology for defining anti-viral B cell repertoires. However, the Ig-cloning step is time-consuming and prevents high-throughput analysis of the B cell repertoire. Novel linear Ig heavy- and light-chain gene expression cassettes were designed to express Ig V(H) and V(L) genes isolated from sorted single B cells as IgG1 antibody without a cloning step. The cassettes contain all essential elements for transcriptional and translational regulation, including CMV promoter, Ig leader sequences, constant region of IgG1 heavy- or Ig light-chain, poly(A) tail and substitutable V(H) or V(L) genes. The utility of these Ig gene expression cassettes was established using synthetic V(H) or V(L) genes from an anti-HIV-1 gp41 mAb 2F5 as a model system, and validated further using V(H) and V(L) genes isolated from cloned EBV-transformed antibody-producing cell lines. Finally, this strategy was successfully used for rapid production of recombinant influenza mAbs from sorted single human plasmablasts after influenza vaccination. These Ig gene expression cassettes constitute a highly efficient strategy for rapid expression of Ig genes for high-throughput screening and analysis without cloning.",,"['Liao, Hua-Xin', 'Levesque, Marc C.', 'Nagel, Ashleigh', 'Dixon, Ashlyn', 'Zhang, Ruijun', 'Walter, Emmanuel', 'Parks, Robert', 'Whitesides, John', 'Marshall, Dawn J.', 'Hwang, Kwan-Ki', 'Yang, Yi', 'Chen, Xi', 'Gao, Feng', 'Munshaw, Supriya', 'Kepler, Thomas B.', 'Denny, Thomas', 'Moody, M. Anthony', 'Haynes, Barton F.']",,,,
,PMC,"Plasmid DNA Vaccine vector design: impact on efficacy, safety and upstream production",http://dx.doi.org/10.1016/j.biotechadv.2009.02.003,PMC2693335,,,"Critical molecular and cellular biological factors impacting design of licensable DNA vaccine vectors that combine high yield and integrity during bacterial production with increased expression in mammalian cells are reviewed. Food and Drug Administration (FDA), World Health Organization (WHO) and European Medical Agencies (EMEA) regulatory guidance’s are discussed, as they relate to vector design and plasmid fermentation. While all new vectors will require extensive preclinical testing to validate safety and performance prior to clinical use, regulatory testing burden for follow-on products can be reduced by combining carefully designed synthetic genes with existing validated vector backbones. A flowchart for creation of new synthetic genes, combining rationale design with bioinformatics, is presented. The biology of plasmid replication is reviewed, and process engineering strategies that reduce metabolic burden discussed. Utilizing recently developed low metabolic burden seed stock and fermentation strategies, optimized vectors can now be manufactured in high yields exceeding 2 g/L, with specific plasmid yields of 5% total dry cell weight.",,"['Williams, James A', 'Carnes, Aaron E', 'Hodgson, Clague P']",,,,
,PMC,Nucleolar targeting: the hub of the matter,http://dx.doi.org/10.1038/embor.2009.14,PMC2658561,,,"The nucleolus is a dynamic structure that has roles in various processes, from ribosome biogenesis to regulation of the cell cycle and the cellular stress response. Such functions are frequently mediated by the sequestration or release of nucleolar proteins. Our understanding of protein targeting to the nucleolus is much less complete than our knowledge of membrane-spanning translocation systems—such as those involved in nuclear targeting—and the experimental evidence reveals that few parallels exist with these better-characterized systems. Here, we discuss the current understanding of nucleolar targeting, explore the types of sequence that control the localization of a protein to the nucleolus, and speculate that certain subsets of nucleolar proteins might act as hub proteins that are able to bind to multiple protein targets. In parallel to other subnuclear structures, such as PML bodies, the proteins that are involved in the formation and maintenance of the nucleolus are inexorably linked to nucleolar trafficking.",,"['Emmott, Edward', 'Hiscox, Julian A']",,,,
,PMC,"SYNCRIP (Synaptotagmin-Binding, Cytoplasmic RNA-Interacting Protein) Is a Host Factor Involved In Hepatitis C virus RNA Replication",http://dx.doi.org/10.1016/j.virol.2009.01.018,PMC3099193,,,"Hepatitis C virus (HCV) RNA replication requires viral nonstructural proteins as well as cellular factors. Recently, a cellular protein, synaptotagmin-binding, cytoplasmic RNA-interacting protein (SYNCRIP), also known as NSAP1, was found to bind HCV RNA and enhance HCV IRES-dependent translation. We investigate whether this protein is also involved in the HCV RNA replication. We found that SYNCRIP was associated with detergent-resistant membrane fractions and colocalized with newly-synthesized HCV RNA. Knock-down of SYNCRIP by siRNA significantly decreased the amount of HCV RNA in the cells containing a subgenomic replicon or a full-length viral RNA. Lastly, an in vitro replication assay after immunodepletion of SYNCRIP showed that SYNCRIP was directly involved in HCV RNA replication. These findings indicate that SYNCRIP has dual functions, participating in both RNA replication and translation in HCV life cycle.",,"['Liu, Helene Minyi', 'Aizaki, Hideki', 'Choi, Keum S.', 'Machida, Keigo', 'Ou, James J.-H.', 'Lai, Michael M.C.']",,,,
,PMC,Discordant memory B cell and circulating anti-Env antibody responses in HIV-1 infection,http://dx.doi.org/10.1073/pnas.0813392106,PMC2644653,,,"Long-lived memory B cells (B(Mem)) provide an archive of historic Ab responses. By contrast, circulating Abs typically decline once the immunogen is cleared. Consequently, circulating Abs can underestimate the nature of cognate humoral immunity. On the other hand, the B(Mem) pool should provide a comprehensive picture of Ab specificities that arise over the entire course of infection. To test this hypothesis, we compared circulating Ab and B(Mem) from natural virus suppressors who control HIV-1 without therapy and maintain a relatively intact immune system. We found high frequencies of B(Mem) specific for the conserved neutralizing CD4 induced or CD4 binding site epitopes of gp120, whereas low Ab titers to these determinants were detected in contemporaneous plasma. These data suggest that plasma Ab repertoires can underestimate the breadth of humoral immunity, and analyses of B(Mem) should be included in studies correlating Ab specificity with protective immunity to HIV-1.",,"['Guan, Yongjun', 'Sajadi, Mohammad M.', 'Kamin-Lewis, Roberta', 'Fouts, Timothy R.', 'Dimitrov, Anthony', 'Zhang, Zhixin', 'Redfield, Robert R.', 'DeVico, Anthony L.', 'Gallo, Robert C.', 'Lewis, George K.']",,,,
,PMC,Chemical Modifications of Antisense Morpholino Oligomers Enhance Their Efficacy against Ebola Virus Infection,http://dx.doi.org/10.1128/AAC.00936-08,PMC2681561,,,"Phosphorodiamidate morpholino oligomers (PMOs) are uncharged nucleic acid-like molecules designed to inactivate the expression of specific genes via the antisense-based steric hindrance of mRNA translation. PMOs have been successful at knocking out viral gene expression and replication in the case of acute viral infections in animal models and have been well tolerated in human clinical trials. We propose that antisense PMOs represent a promising class of therapeutic agents that may be useful for combating filoviral infections. We have previously shown that mice treated with a PMO whose sequence is complementary to a region spanning the start codon of VP24 mRNA were protected against lethal Ebola virus challenge. In the present study, we report on the abilities of two additional VP24-specific PMOs to reduce the cell-free translation of a VP24 reporter, to inhibit the in vitro replication of Ebola virus, and to protect mice against lethal challenge when the PMOs are delivered prior to infection. Additionally, structure-activity relationship evaluations were conducted to assess the enhancement of antiviral efficacy associated with PMO chemical modifications that included conjugation with peptides of various lengths and compositions, positioning of conjugated peptides to either the 5′ or the 3′ terminus, and the conferring of charge modifications by the addition of piperazine moieties. Conjugation with arginine-rich peptides greatly enhanced the antiviral efficacy of VP24-specific PMOs in infected cells and mice during lethal Ebola virus challenge.",,"['Swenson, Dana L.', 'Warfield, Kelly L.', 'Warren, Travis K.', 'Lovejoy, Candace', 'Hassinger, Jed N.', 'Ruthel, Gordon', 'Blouch, Robert E.', 'Moulton, Hong M.', 'Weller, Dwight D.', 'Iversen, Patrick L.', 'Bavari, Sina']",,,,
,PMC,"[(18)F]- and [(11)C]-Labeled N-benzyl-isatin sulfonamide analogues as PET tracers for apoptosis: synthesis, radiolabeling mechanism, and in vivo imaging of apoptosis in Fas-treated mice",http://dx.doi.org/10.1039/b819024k,PMC3075237,,,"The radiolabeled isatin sulfonamide caspase-3 inhibitor, [(18)F]2 (WC-II-89), is a potential PET radiotracer for noninvasive imaging of apoptosis. The radiolabeling mechanism was studied by (13)C NMR, ESI/MS, and computational calculations. It was found that the high electrophilicity of the C3 carbonyl group in the isatin ring, which served as a trap for [(18)F]fluoride, was responsible for the failure of the radiolabeling via nucleophilic substitution of the mesylate group in 7a by [(18)F]fluoride. Once treated with a strong base, 7a opened the isatin ring completely to form an isatinate intermediate 16, which lost the ability to trap [(18)F]fluoride, thereby allowing the displacement of the mesylate group to afford the (18)F-labeled isatinate 17. [(18)F]17 can be converted to isatin [(18)F]2 efficiently under acidic conditions. The ring-opening and re-closure of the isatin ring under basic and acidic conditions were confirmed by reversed phase HPLC analysis, ESI/MS and (13)C NMR studies. Computational studies of model compounds also support the above proposed mechanism. Similarly, the ring-opening and re-closure method was used successfully in the synthesis of the (11)C labeled isatin sulfonamide analogue [(11)C]4 (WC-98). A microPET imaging study using [(11)C]4 in the Fas liver apoptosis model demonstrated retained activity in the target organ (liver) of the treated mice. Increased caspase-3 activation in the liver was verified by the fluorometric caspase-3 enzyme assay. Therefore, this study provides a useful method for radio-synthesis of isatin derivative radiotracers for PET and SPECT studies, and [(11)C]4 is a potential PET radiotracer for noninvasive imaging of apoptosis.",,"['Zhou, Dong', 'Chu, Wenhua', 'Chen, Delphine L.', 'Wang, Qi', 'Reichert, David E.', 'Rothfuss, Justin', ""D'Avignon, Andre"", 'Welch, Michael J.', 'Mach, Robert H.']",,,,
,PMC,Synthesis and pharmacological evaluation of (2-oxaadamant-1-yl)amines,http://dx.doi.org/10.1016/j.bmc.2009.02.007,PMC3217223,,,"The synthesis of several (2-oxaadamant-1-yl)amines is reported. They were evaluated as NMDA receptor antagonists and several of them were more active than amantadine, but none was more potent than memantine. None of the tested compounds displayed antiviral activity. Two of the derivatives showed a significant level of trypanocidal activity.",,"['Duque, María D.', 'Camps, Pelayo', 'Profire, Lenuta', 'Montaner, Silvia', 'Vázquez, Santiago', 'Sureda, Francesc X.', 'Mallol, Jordi', 'López-Querol, Marta', 'Naesens, Lieve', 'Clercq, Erik De', 'Prathalingam, S. Radhika', 'Kelly, John M.']",,,,
,PMC,Population-based simulations of influenza pandemics: validity and significance for public health policy,http://dx.doi.org/10.2471/BLT.07.050203,PMC2672572,,,"OBJECTIVE: To examine the validity and usefulness of pandemic simulations aimed at informing practical decision-making in public health. METHODS: We recruited a multidisciplinary group of nine experts to assess a case-study simulation of influenza transmission in a Swedish county. We used a non-statistical nominal group technique to generate evaluations of the plausibility, formal validity (verification) and predictive validity of the simulation. A health-effect assessment structure was used as a framework for data collection. FINDINGS: The unpredictability of social order during disasters was not adequately addressed by simulation methods; even minor disruptions of the social order may invalidate key infrastructural assumptions underpinning current pandemic simulation models. Further, a direct relationship between model flexibility and computation time was noted. Consequently, simulation methods cannot, in practice, support integrated modifications of microbiological, epidemiological and spatial submodels or handle multiple parallel scenarios. CONCLUSION: The combination of incomplete surveillance data and simulation methods that neglect social dynamics limits the ability of national public health agencies to provide policy-makers and the general public with the critical and timely information needed during a pandemic.",,"['Timpka, Toomas', 'Eriksson, Henrik', 'Gursky, Elin A', 'Nyce, James M', 'Morin, Magnus', 'Jenvald, Johan', 'Strömgren, Magnus', 'Holm, Einar', 'Ekberg, Joakim']",,,,
,PMC,Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase,http://dx.doi.org/10.1073/pnas.0808790106,PMC2651275,,,"The N7-methylguanosine (m7G) cap is the defining structural feature of eukaryotic mRNAs. Most eukaryotic viruses that replicate in the cytoplasm, including coronaviruses, have evolved strategies to cap their RNAs. In this report, we used a yeast genetic system to functionally screen for the cap-forming enzymes encoded by severe acute respiratory syndrome (SARS) coronavirus and identified the nonstructural protein (nsp) 14 of SARS coronavirus as a (guanine-N7)-methyltransferase (N7-MTase) in vivo in yeast cells and in vitro using purified enzymes and RNA substrates. Interestingly, coronavirus nsp14 was previously characterized as a 3′-to-5′ exoribonuclease, and by mutational analysis, we mapped the N7-MTase domain to the carboxy-terminal part of nsp14 that shows features conserved with cellular N7-MTase in structure-based sequence alignment. The exoribonuclease active site was dispensable but the exoribonuclease domain was required for N7-MTase activity. Such combination of the 2 functional domains in coronavirus nsp14 suggests that it may represent a novel form of RNA-processing enzymes. Mutational analysis in a replicon system showed that the N7-MTase activity was important for SARS virus replication/transcription and can thus be used as an attractive drug target to develop antivirals for control of coronaviruses including the deadly SARS virus. Furthermore, the observation that the N7-MTase of RNA life could function in lieu of that in DNA life provides interesting evolutionary insight and practical possibilities in antiviral drug screening.",,"['Chen, Yu', 'Cai, Hui', ""Pan, Ji'an"", 'Xiang, Nian', 'Tien, Po', 'Ahola, Tero', 'Guo, Deyin']",,,,
,PMC,C-terminal domain of SARS-CoV main protease can form a 3D domain-swapped dimer,http://dx.doi.org/10.1002/pro.76,PMC2762595,,,"SARS coronavirus main protease (M(pro)) plays an essential role in the extensive proteolytic processing of the viral polyproteins (pp1a and pp1ab), and it is an important target for anti-SARS drug development. We have reported that both the M(pro) C-terminal domain alone (M(pro)-C) and the N-finger deletion mutant of M(pro) (M(pro)-Δ7) exist as a stable dimer and a stable monomer (Zhong et al., J Virol 2008; 82:4227-4234). Here, we report structures of both M(pro)-C monomer and dimer. The structure of the M(pro)-C monomer is almost identical to that of the C-terminal domain in the crystal structure of M(pro). Interestingly, the M(pro)-C dimer structure is characterized by 3D domain-swapping, in which the first helices of the two protomers are interchanged and each is enwrapped by four other helices from the other protomer. Each folding subunit of the M(pro)-C domain-swapped dimer still has the same general fold as that of the M(pro)-C monomer. This special dimerization elucidates the structural basis for the observation that there is no exchange between monomeric and dimeric forms of M(pro)-C and M(pro)-Δ7.",,"['Zhong, Nan', 'Zhang, Shengnan', 'Xue, Fei', 'Kang, Xue', 'Zou, Peng', 'Chen, Jiaxuan', 'Liang, Chao', 'Rao, Zihe', 'Jin, Changwen', 'Lou, Zhiyong', 'Xia, Bin']",,,,
,PMC,The spike protein of SARS-CoV — a target for vaccine and therapeutic development,http://dx.doi.org/10.1038/nrmicro2090,PMC2750777,,,"Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease caused by a novel coronavirus, SARS-coronavirus (SARS-CoV). The SARS-CoV spike (S) protein is composed of two subunits; the S1 subunit contains a receptor-binding domain that engages with the host cell receptor angiotensin-converting enzyme 2 and the S2 subunit mediates fusion between the viral and host cell membranes. The S protein plays key parts in the induction of neutralizing-antibody and T-cell responses, as well as protective immunity, during infection with SARS-CoV. In this Review, we highlight recent advances in the development of vaccines and therapeutics based on the S protein.",,"['Du, Lanying', 'He, Yuxian', 'Zhou, Yusen', 'Liu, Shuwen', 'Zheng, Bo-Jian', 'Jiang, Shibo']",,,,
,PMC,"INGN 007, an oncolytic adenovirus vector, replicates in Syrian hamsters but not mice: comparison of biodistribution studies",http://dx.doi.org/10.1038/cgt.2009.6,PMC3433952,,,"Preclinical biodistribution studies with INGN 007, an oncolytic adenovirus (Ad) vector, supporting an early stage clinical trial were conducted in Syrian hamsters, which are permissive for Ad replication, and mice, which are a standard model for assessing toxicity and biodistribution of replication-defective (RD) Ad vectors. Vector dissemination and pharmacokinetics following intravenous administration were examined by real-time PCR in nine tissues and blood at five time points spanning 1 year. Select organs were also examined for the presence of infectious vector/virus. INGN 007 (VRX-007), wild-type Ad5 and AdCMVpA (an RD vector) were compared in the hamster model, whereas only INGN 007 was examined in mice. DNA of all vectors was widely disseminated early after injection, but decayed rapidly in most organs. In the hamster model, DNA of INGN 007 and Ad5 was more abundant than that of the RD vector AdCMVpA at early times after injection, but similar levels were seen later. An increased level of INGN 007 and Ad5 DNA but not AdCMVpA DNA in certain organs early after injection, and the presence of infectious INGN 007 and Ad5 in lung and liver samples at early times after injection, strongly suggests that replication of INGN 007 and Ad5 occurred in several Syrian hamster organs. There was no evidence of INGN 007 replication in mice. In addition to providing important information about INGN 007, the results underscore the utility of the Syrian hamster as a permissive immunocompetent model for Ad5 pathogenesis and oncolytic Ad vectors.",,"['Ying, B', 'Toth, K', 'Spencer, JF', 'Meyer, J', 'Tollefson, AE', 'Patra, D', 'Dhar, D', 'Shashkova, EV', 'Kuppuswamy, M', 'Doronin, K', 'Thomas, MA', 'Zumstein, LA', 'Wold, WSM', 'Lichtenstein, DL']",,,,
,PMC,The Influenza Virus Enigma,http://dx.doi.org/10.1016/j.cell.2009.01.029,PMC2971533,,,"Both seasonal and pandemic influenza continue to challenge both scientists and clinicians. Drug-resistant H1N1 influenza viruses have dominated the 2009 flu season, and the H5N1 avian influenza virus continues to kill both people and poultry in Eurasia. Here, we discuss the pathogenesis and transmissibility of influenza viruses and we emphasize the need to find better predictors of both seasonal and potentially pandemic influenza.",,"['Salomon, Rachelle', 'Webster, Robert G.']",,,,
,PMC,Learning from the Viral Journey: How to Enter Cells and How to Overcome Intracellular Barriers to Reach the Nucleus,http://dx.doi.org/10.1208/s12248-009-9080-9,PMC2664881,,,"Viruses deliver their genome into host cells where they subsequently replicate and multiply. A variety of relevant strategies have evolved by which viruses gain intracellular access and utilize cellular machinery for the synthesis of their genome. Therefore, the viral journey provides insight into the cell’s trafficking machinery and how it can be best exploited to improve nonviral gene delivery systems. This review summarizes viral internalization pathways and intracellular trafficking of viruses, with an emphasis on the endosomal escape processes of nonenveloped viruses. Intracellular events from viral entry through nuclear delivery of the viral complementary DNA are also discussed.",,"['Mudhakir, Diky', 'Harashima, Hideyoshi']",,,,
,PMC,Host Responses from Innate to Adaptive Immunity after Vaccination: Molecular and Cellular Events,http://dx.doi.org/10.1007/s10059-009-0015-1,PMC6280669,,,"The availability of effective vaccines has had the most profound positive effect on improving the quality of public health by preventing infectious diseases. Despite many successful vaccines, there are still old and new emerging pathogens against which there is no vaccine available. A better understanding of how vaccines work for providing protection will help to improve current vaccines as well as to develop effective vaccines against pathogens for which we do not have a proper means to control. Recent studies have focused on innate immunity as the first line of host defense and its role in inducing adaptive immunity; such studies have been an intense area of research, which will reveal the immunological mechanisms how vaccines work for protection. Toll-like receptors (TLRs), a family of receptors for pathogen-associated molecular patterns on cells of the innate immune system, play a critical role in detecting and responding to microbial infections. Importantly, the innate immune system modulates the quantity and quality of long-term T and B cell memory and protective immune responses to pathogens. Limited studies suggest that vaccines which mimic natural infection and/or the structure of pathogens seem to be effective in inducing long-term protective immunity. A better understanding of the similarities and differences of the molecular and cellular events in host responses to vaccination and pathogen infection would enable the rationale for design of novel preventive measures against many challenging pathogens.",,"['Kang, Sang-Moo', 'Compans, Richard W.']",,,,
,PMC,Recombinant measles virus-HPV vaccine candidates for prevention of cervical carcinoma,http://dx.doi.org/10.1016/j.vaccine.2009.01.061,PMC3487399,,,"Cervical cancer is mainly associated with HPV genotype 16 infection. Recombinant measles virus (rMV) expressing HPV genotype 16 L1 capsid protein was generated by construction of an antigenomic plasmid, followed by rescue using the human “helper” cell line 293-3-46. In cell cultures the recombinant MV-L1 virus replicated practically as efficiently as the standard attenuated MV established as commercial vaccine, devoid of the transgene. The high genetic stability of MVb2-L1 was confirmed by 10 serial viral transfers in cell culture. In transgenic mice expressing the MV receptor CD46 the recombinant induced strong humoral immune responses against both MV and HPV; the antibodies against L1 exhibited mainly neutralizing capacity. Our data suggest that MV is a promising vehicle for development of inexpensive and efficient vaccines protecting from HPV infection.",,"['Cantarella, Giuseppina', 'Liniger, Matthias', 'Zuniga, Armando', 'Schiller, John T.', 'Billeter, Martin', 'Naim, Hussein Y.', 'Glueck, Reinhard']",,,,
,PMC,CD4 T-Cell-Mediated Heterologous Immunity between Mycobacteria and Poxviruses,http://dx.doi.org/10.1128/JVI.02393-08,PMC2663272,,,"The bacillus Calmette-Guerin (BCG) strain of Mycobacterium bovis is used in many parts of the world as a vaccine against Mycobacterium tuberculosis. Some epidemiological evidence has suggested that BCG immunization may have unpredicted effects on resistance to other pathogens. We show here in a mouse model that BCG immunization followed by antibiotic treatment to clear the host of the pathogen rendered three strains of mice partially resistant to infection with vaccinia virus (VV) but not to lymphocytic choriomeningitis virus (LCMV). VV-challenged BCG-immune mice developed a striking splenomegaly and elevated CD4 and CD8 T-cell responses by 6 days postinfection (p.i.). However, resistance to VV infection could be seen as early as 1 to 2 days p.i. and was lost after antibody depletion of CD4 T-cell populations. BCG- but not LCMV-immune memory phenotype CD4 T cells preferentially produced gamma interferon (IFN-γ) in vivo after VV challenge. In contrast, LCMV-immune CD8 T cells preferentially produced IFN-γ in vivo in response to VV infection. In BCG-immune mice the resistance to VV infection and VV-induced CD4 T-cell IFN-γ production were ablated by cyclosporine A, which inhibits signaling through the T-cell receptor. This study therefore demonstrates CD4 T-cell-mediated heterologous immunity between a bacterium and virus. Further, it poses the question of whether BCG immunization of humans alters resistance to unrelated pathogens.",,"['Mathurin, Keisha S.', 'Martens, Gregory W.', 'Kornfeld, Hardy', 'Welsh, Raymond M.']",,,,
,PMC,"A recombinant, infectious human parainfluenza virus type 3 expressing the enhanced green fluorescent protein for use in high-throughput antiviral assays",http://dx.doi.org/10.1016/j.antiviral.2009.01.001,PMC2701465,,,"The ability to rescue an infectious, recombinant, negative-stranded, RNA virus from a cDNA clone, has led to new opportunities for measuring viral replication from a viral expressed reporter gene. In this study, the enhanced green fluorescent protein (EGFP) gene was inserted into the human parainfluenza virus type 3 (HPIV-3) antigenome and a recombinant, infectious virus was rescued. Maximum EGFP expression levels, measured by fluorescence, were seen at day 3. Comparison of a three-day, viral expressed EGFP fluorescence assay to a seven-day, neutral red assay, based on complete cell destruction in virus infected MA-104 cells, yielded Z′-factor values of 0.83 and 0.70, respectively. A three-day, endpoint EGFP-based antiviral assay and a seven-day, endpoint neutral red based antiviral assay were run in parallel to establish antiviral sensitivity profiles of 23 compounds based on selective index (SI) values. Using an SI threshold of 10, the EGFP-based antiviral assay had a sensitivity of 100% and a specificity of 54%. Thus, the use of an EGFP-based antiviral assay for testing potential antiviral compounds against HPIV-3 in a high-throughput format may be justified.",,"['Roth, Jason P.', 'Li, Joseph K.-K.', 'Smee, Donald F.', 'Morrey, John D.', 'Barnard, Dale L.']",,,,
,PMC,Lung cancer: Developmental networks gone awry?,,PMC2930783,,,High-throughput genomic data for both lung development and lung cancer continue to accumulate. Significant molecular intersection between these two processes has been hypothesized due to overlap in phenotypes and genomic variation. Examining the network biology of both cancer and development of the lung may shed functional light on the individual signaling modules involved. Stem cell biology may explain a portion of this network intersection and consequently studying lung organogenesis may have relevance for understanding lung cancer. This review summarizes our understanding of the potential overlapping mechanisms involved in lung development and lung tumorigenesis.,,"['Dong, Jie', 'Kislinger, Thomas', 'Jurisica, Igor', 'Wigle, Dennis A.']",,,,
,PMC,"Acute Exacerbations of Asthma: Epidemiology, Biology and the Exacerbation-Prone Phenotype",http://dx.doi.org/10.1111/j.1365-2222.2008.03157.x,PMC2730743,,,"Asthma is a highly prevalent chronic respiratory disease affecting 300 million people worldwide. A significant fraction of the cost and morbidity of asthma derives from acute care for asthma exacerbations. In the United States alone, there are approximately 15.0 million outpatient visits, 2 million emergency room visits, and 500,000 hospitalizations each year for management of acute asthma. Common respiratory viruses, especially rhinoviruses, cause the majority of exacerbations in children and adults. Infection of airway epithelial cells with rhinovirus causes the release of pro-inflammatory cytokines and chemokines, as well as recruitment of inflammatory cells, particularly neutrophils, lymphocytes, and eosinophils. The host response to viral infection is likely to influence susceptibility to asthma exacerbation. Having had at least one exacerbation is an important risk factor for recurrent exacerbations suggesting an “exacerbation-prone” subset of asthmatics. Factors underlying for the “exacerbation-prone” phenotype are incompletely understood but include extrinsic factors: cigarette smoking, medication noncompliance, psychosocial factors, and co-morbidities such as gastroesophageal reflux disease, rhinosinusitis, obesity, and intolerance to non-steroidal anti-inflammatory medications; as well as intrinsic factors such as deficient epithelial cell production of the anti-viral type I interferons (IFN-α and IFN-β). A better understanding of the biologic mechanisms of host susceptibility to recurrent exacerbations will be important for developing more effective preventions and treatments aimed at reducing the significant cost and morbidity associated with this important global health problem.",,"['Dougherty, RH', 'Fahy, John V']",,,,
,PMC,Use of Low-Molecular–Weight Heparin to Decrease Mortality in Mice after Intracardiac Injection of Tumor Cells,,PMC2703139,,,"Intracardiac injection of human tumor cells into anesthetized nude mice is an established model of bone metastasis. However, intracardiac injection of some human tumor cell lines cause acute neurologic signs and high mortality, making some potentially relevant tumor cell lines unusable for investigation. We showed that intracardiac injection of tumor cells can induce a hypercoagulable state leading to platelet consumption and thromboemboli formation and that pretreatment with intravenous injection of low-molecular–weight heparin (LMWH; enoxaparin) blocks this state. In addition, intravenous injection of enoxaparin before intracardiac injection with 2 different small-cell lung carcinoma lines, H1975 and H2126, dramatically decreased mouse mortality while still generating bone metastases. Therefore, reduction of mortality by pretreatment with LMWH increases the types of cells that can be studied in this metastasis model and decreases the number of animals used.",,"['Stocking, Kim L', 'Jones, Jon C', 'Everds, Nancy E', 'Buetow, Bernard S', 'Roudier, Martine P', 'Miller, Robert E']",,,,
,PMC,Evaluation of Buprenorphine in a Postoperative Pain Model in Rats,,PMC2703135,,,"We evaluated the commonly prescribed analgesic buprenorphine in a postoperative pain model in rats, assessing acute postoperative pain relief, rebound hyperalgesia, and the long-term effects of postoperative opioid treatment on subsequent opioid exposure. Rats received surgery (paw incision under isoflurane anesthesia), sham surgery (anesthesia only), or neither and were treated postoperatively with 1 of several doses of subcutaneous buprenorphine. Pain sensitivity to noxious and nonnoxious mechanical stimuli at the site of injury (primary pain) was assessed at 1, 4, 24, and 72 h after surgery. Pain sensitivity at a site distal to the injury (secondary pain) was assessed at 24 and 72 h after surgery. Rats were tested for their sensitivity to the analgesic and locomotor effects of morphine 9 to 10 d after surgery. Buprenorphine at 0.05 mg/kg SC was determined to be the most effective; this dose induced isoalgesia during the acute postoperative period and the longest period of pain relief, and it did not induce long-term changes in opioid sensitivity in 2 functional measures of the opioid system. A lower dose of buprenorphine (0.01 mg/kg SC) did not meet the criterion for isoalgesia, and a higher dose (0.1 mg/kg SC) was less effective in pain relief at later recovery periods and induced a long-lasting opioid tolerance, indicating greater neural adaptations. These results support the use of 0.05 mg/kg SC buprenorphine as the upper dose limit for effective treatment of postoperative pain in rats and suggest that higher doses produce long-term effects on opioid sensitivity.",,"['Curtin, Leslie I', 'Grakowsky, Julie A', 'Suarez, Mauricio', 'Thompson, Alexis C', 'DiPirro, Jean M', 'Martin, Lisa BE', 'Kristal, Mark B']",,,,
,PMC,Extreme Susceptibility of African Naked Mole Rats (Heterocephalus glaber) to Experimental Infection with Herpes Simplex Virus Type 1,,PMC2703134,,,"Herpes simplex virus type 1 (HSV1) is widely used as a gene delivery vector in a variety of laboratory animals. In a recent study, a thymidine-kinase–inactive (replication-conditional) HSV1 used as a delivery vector was lethal in naked mole rats, whereas mice infected with the identical virus showed no adverse effects. This result prompted us to undertake a controlled comparative histologic study of the effect of HSV1 infection on naked mole rats and mice. Replication-competent and replication-conditional HSV1 caused widespread inflammation and necrosis in multiple organ systems of naked mole rats but not mice; naked mole rats infected with replication-defective virus showed no adverse effects. We conclude that the lethality of HSV1 for naked mole rats is likely the result of overwhelming infection, possibly in part due to this species’ natural lack of proinflammatory neuropeptides at the initial site of infection.",,"['Artwohl, James', 'Ball-Kell, Susan', 'Valyi-Nagy, Tibor', 'Wilson, Steven P', 'Lu, Ying', 'Park, Thomas J']",,,,
,PMC,Rhinovirus and the Initiation of Asthma,http://dx.doi.org/10.1097/ACI.0b013e32831f8f1b,PMC2760477,,,"PURPOSE OF REVIEW: Virus-induced wheezing in infancy is a risk factor for asthma, and recent studies have highlighted the role of rhinoviruses in causing acute illnesses and as a possible contributing factor to chronic asthma. RECENT FINDINGS: Rhinoviruses (HRV) have long been known as the most common cause of the common cold in infants and children. Recent developments in molecular diagnostics have led to the discovery of new viruses, and have also provided data to implicate HRV as important causes of lower respiratory infections and acute virus-induced wheezing in preschool children. In addition, HRV-induced wheezing episodes appear to identify children who are at increased risk for the subsequent development of childhood asthma. SUMMARY: Collectively, these findings raise the possibility that LRI with pathogens such as HRV and RSV could participate in the causation of asthma, especially in children with suboptimal antiviral defenses. A variety of experimental models and clinical studies have been used to identify possible mechanisms related to the infection and the ensuing host response that could disturb normal lung and immunologic development to promote asthma. Defining these relationships could lead to new therapeutic and preventive approaches to common forms of childhood asthma.",,"Gern, James E.",,,,
,PMC,Polyether ionophores: broad-spectrum and promising biologically active molecules for the control of drug-resistant bacteria and parasites,http://dx.doi.org/10.1517/17460440802661443,PMC4896753,,,"BACKGROUND: As multidrug-resistant (MDR) pathogens continue to emerge, there is a substantial amount of pressure to identify new drug candidates. Carboxyl polyethers, also referred to as polyether antibiotics, are a unique class of compounds with outstanding potency against a variety of critical infectious disease targets including protozoa, bacteria and viruses. The characteristics of these molecules that are of key interest are their selectivity and high potency against several MDR etiological agents. OBJECTIVE: Although many studies have been published about carboxyl polyether antibiotics, there are no recent reviews of this class of drugs. The purpose of this review is to provide the reader with an overview of the spectrum of activity of polyether antibiotics, their mechanism of action, toxicity and potential as drug candidates to combat drug-resistant infectious diseases. CONCLUSION: Polyether ionophores show a high degree of promise for the potential control of drug-resistant bacterial and parasitic infections. Despite the long history of use of this class of drugs, very limited medicinal chemistry and drug optimization studies have been reported, thus leaving the door open to these opportunities in the future. Scifinder and PubMed were the main search engines used to locate articles relevant to the topic presented in the present review. Keywords used in our search were specific names of each of the 88 compounds presented in the review as well as more general terms such as polyethers, ionophores, carboxylic polyethers and polyether antibiotics.",,"['Kevin, Dion A', 'Meujo, Damaris AF', 'Hamann, Mark T']",,,,
,PMC,Inter-Facility Patient Transfers in Ontario: Do You Know What Your Local Ambulance Is Being Used For?,,PMC2653709,,,"BACKGROUND: Little is known about inter-facility patient transfers in populations. In 2003, detailed information about inter-facility patient transfers began to be systematically collected in Ontario. METHODOLOGY: The authors undertook a descriptive examination of inter-facility patient transfers using a newly created population-based information system. RESULTS: Approximately 1,000 inter-facility patient transfers occur in Ontario each day, and every day and a half, the total distance travelled for these transfers equals the distance around the earth's circumference. The annual cost for patient transfers is approximately $283 million. Most common were routine and non-urgent inter-facility patient transfers. Eighty-five thousand patients (24.3% of transferred patients) were transported between healthcare facilities for dialysis appointments, appointments with physicians and return trips home. Patients with circulatory conditions were the most commonly transferred diagnostic group. Although 70% of all transfers were within 25 kilometres, some were for longer distances: for example, those involving pregnant women and newborn babies required travelling a median distance of 40.3 kilometres for continued care. Cardiac patients (54,000 patient transfers per year) travelled a median of 24.2 kilometres to reach a catheterization lab for treatment and further investigation. There was considerable lateral movement between academic health sciences centres (AHSCs). Over 16,000 patients per year (4.7% of all transfers) were transferred from one AHSC to another, predominantly for cardiac care. DISCUSSION: Patients in Ontario are often transferred between healthcare facilities. Most transfers are for routine, non–life-threatening reasons, using the Emergency Medical Services (EMS) system. This practice diverts resources from more emergent requests. Although patient transportation is a necessary part of any healthcare system, the results of this study highlight the current demands on a system that was not intended for the volume of inter-facility patient transfers it is supporting. These results call into question the use of sophisticated, highly trained, expensive patient transfer resources to provide routine medical services in Ontario.",,"['Robinson, Victoria', 'Goel, Vivek', 'MacDonald, Russell D.', 'Manuel, Doug']",,,,
,PMC,Differentiated Human Alveolar Type II Cells Secrete Antiviral IL-29 (IFN-λ1) in Response to Influenza A Infection(),,PMC4041086,,,"Alveolar type II epithelial cells (ATIIs) are one of the primary targets for influenza A pneumonia. The lack of a culture system for maintaining differentiated ATIIs hinders our understanding of pulmonary innate immunity during viral infection. We studied influenza A virus (IAV)-induced innate immune responses in differentiated primary human ATIIs and alveolar macrophages (AMs). Our results indicate that ATIIs, but not AMs, support productive IAV infection. Viral infection elicited strong inflammatory chemokine and cytokine responses in ATIIs, including secretion of IL-8, IL-6, MCP-1, RANTES, and MIP-1β, but not TNF-α, whereas AMs secreted TNF-α as well as other cytokines in response to infection. Wild-type virus A/PR/8/34 induced a greater cytokine response than reassortant PR/8 virus, A/Phil/82, despite similar levels of replication. IAV infection increased mRNA expression of IFN genes IFN-β, IL-29 (IFN-λ1), and IL-28A (IFN-λ2). The major IFN protein secreted by type II cells was IL-29 and ATIIs appear to be a major resource for production of IL-29. Administration of IL-29 and IFN-β before infection significantly reduced the release of infectious viral particles and CXC and CC chemokines. IL-29 treatment of type II cells induced mRNA expression of antiviral genes MX1, OAS, and ISG56 but not IFN-β. IL-29 induced a dose-dependent decrease of viral nucleoprotein and an increase of antiviral genes but not IFN-β. These results suggest that IL-29 exerts IFN-β-independent protection in type II cells through direct activation of antiviral genes during IAV infection.",,"['Wang, Jieru', 'Oberley-Deegan, Rebecca', 'Wang, Shuanglin', 'Nikrad, Mrinalini', 'Funk, C. Joel', 'Hartshorn, Kevan L.', 'Mason, Robert J.']",,,,
,PMC,Intersection of Gene Therapy and Progenitor Cell Biology in the Lung,http://dx.doi.org/10.1038/mt.2008.285,PMC2835047,,,,,"Weiss, Daniel J",,,,
,PMC,SARS Coronavirus Spike Protein-Induced Innate Immune Response occurs via Activation of the NF-κB pathway in Human Monocyte Macrophages in vitro,http://dx.doi.org/10.1016/j.virusres.2009.01.005,PMC2699111,,,"A purified recombinant spike (S) protein was studied for its effect on stimulating human peripheral blood monocyte macrophages (PBMC). We examined inflammatory gene mRNA abundances found in S protein-treated PBMC using gene arrays. We identified differential mRNA abundances of genes with functional properties associated with antiviral (CXCL10) and inflammatory (IL-6, IL-8) responses. We confirmed cytokine mRNA increases by real time quantitative(q) RT-PCR or ELISA. We further analyzed the sensitivity and specificity of the prominent IL-8 response. By real time qRT-PCR, S protein was shown to stimulate IL-8 mRNA accumulation in a dose dependent manner while treatment with E protein did not. Also, titration of S protein-specific production and secretion of IL-8 by ELISA showed that the dose of 5.6nM of S produced a significant increase in IL-8 (p=0.003) compared to mock-treated controls. The increase in IL-8 stimulated by a concentration of 5.6 nM of S was comparable to concentrations seen for S protein binding to ACE2 or to neutralizing monoclonal antibody suggesting a physiological relevance. An NF-κB inhibitor, TPCK (N-Tosyl-L-Phenylalanine Chloromethyl Ketone) could suppress IL-8 production and secretion in response to S protein in PBMC and THP-1 cells and in HCoV-229E virus-infected PBMC. Activation and translocation of NF-κB was shown to occur rapidly following exposure of PBMC or THP-1 cells to S protein using a highly sensitive assay for active nuclear NF-κB p65 transcription factor. The results further suggested that released or secreted S protein could activate blood monocytes thru recognition by toll-like receptor (TLR)2 ligand.",,"['Dosch, Susan F.', 'Mahajan, Supriya D.', 'Collins, Arlene R.']",,,,
,PMC,"Induction of a Striking Systemic Cytokine Cascade prior to Peak Viremia in Acute Human Immunodeficiency Virus Type 1 Infection, in Contrast to More Modest and Delayed Responses in Acute Hepatitis B and C Virus Infections",http://dx.doi.org/10.1128/JVI.01844-08,PMC2663284,,,"Characterization of the immune responses induced in the initial stages of human immunodeficiency virus type 1 (HIV-1) infection is of critical importance for an understanding of early viral pathogenesis and prophylactic vaccine design. Here, we used sequential plasma samples collected during the eclipse and exponential viral expansion phases from subjects acquiring HIV-1 (or, for comparison, hepatitis B virus [HBV]or hepatitis C virus [HCV]) to determine the nature and kinetics of the earliest systemic elevations in cytokine and chemokine levels in each infection. Plasma viremia was quantitated over time, and levels of 30 cytokines and chemokines were measured using Luminex-based multiplex assays and enzyme-linked immunosorbent assays. The increase in plasma viremia in acute HIV-1 infection was found to be associated with elevations in plasma levels of multiple cytokines and chemokines, including rapid and transient elevations in alpha interferon (IFN-α) and interleukin-15 (IL-15) levels; a large increase in inducible protein 10 (IP-10) levels; rapid and more-sustained increases in tumor necrosis factor alpha and monocyte chemotactic protein 1 levels; more slowly initiated elevations in levels of additional proinflammatory factors including IL-6, IL-8, IL-18, and IFN-γ; and a late-peaking increase in levels of the immunoregulatory cytokine IL-10. Notably, there was comparatively little perturbation in plasma cytokine levels during the same phase of HBV infection and a delayed response of more intermediate magnitude in acute HCV infection, indicating that the rapid activation of a striking systemic cytokine cascade is not a prerequisite for viral clearance (which occurs in a majority of HBV-infected individuals). The intense early cytokine storm in acute HIV-1 infection may have immunopathological consequences, promoting immune activation, viral replication, and CD4(+) T-cell loss.",,"['Stacey, Andrea R.', 'Norris, Philip J.', 'Qin, Li', 'Haygreen, Elizabeth A.', 'Taylor, Elizabeth', 'Heitman, John', 'Lebedeva, Mila', 'DeCamp, Allan', 'Li, Dongfeng', 'Grove, Douglas', 'Self, Steven G.', 'Borrow, Persephone']",,,,
,PMC,Organ-Specific Attenuation of Murine Hepatitis Virus Strain A59 by Replacement of Catalytic Residues in the Putative Viral Cyclic Phosphodiesterase ns2,http://dx.doi.org/10.1128/JVI.02203-08,PMC2663271,,,"The Murine hepatitis virus (MHV) strain A59 ns2 protein is a 30-kDa nonstructural protein that is expressed from a subgenomic mRNA in the cytoplasm of virus-infected cells. Its homologs are also encoded in other closely related group 2a coronaviruses and more distantly related toroviruses. Together, these proteins comprise a subset of a large superfamily of 2H phosphoesterase proteins that are distinguished by a pair of conserved His-x-Thr/Ser motifs encompassing catalytically important residues. We have used a vaccinia virus-based reverse genetic system to produce recombinant viruses encoding ns2 proteins with single-amino-acid substitutions in, or adjacent to, these conserved motifs, namely, inf-ns2 H46A, inf-ns2 S48A, inf-ns2-S120A, and inf-ns2-H126R. All of the mutant viruses replicate in mouse 17 clone 1 fibroblast cells and mouse embryonic cells to the same extent as the parental wild-type recombinant virus, inf-MHV-A59. However, compared to inf-MHV-A59, the inf-ns2 H46A and inf-ns2-H126R mutants are highly attenuated for replication in mouse liver following intrahepatic inoculation. Interestingly, none of the mutant viruses were attenuated for replication in mouse brain following intracranial inoculation. These results show that the ns2 protein of MHV-A59 has an important role in virus pathogenicity and that a substitution of the histidine residues of the MHV-A59 ns2 His-x-Thr/Ser motifs is critical for virus virulence in the liver but not in the brain. This novel phenotype suggests a strategy to investigate the function of the MHV-A59 ns2 protein involving the search for organ-specific proteins or RNAs that react differentially to wild-type and mutant ns2 proteins.",,"['Roth-Cross, Jessica K.', 'Stokes, Helen', 'Chang, Guohui', 'Chua, Ming Ming', 'Thiel, Volker', 'Weiss, Susan R.', 'Gorbalenya, Alexander E.', 'Siddell, Stuart G.']",,,,
,PMC,Animal models for the study of influenza pathogenesis and therapy,http://dx.doi.org/10.1016/j.antiviral.2008.12.014,PMC2700745,,,"Influenza A viruses causes a variety of illnesses in humans. The most common infection, seasonal influenza, is usually a mild, self-limited febrile syndrome, but it can be more severe in infants, the elderly, and immunodeficient persons, in whom it can progress to severe viral pneumonitis or be complicated by bacterial superinfection, leading to pneumonia and sepsis. Seasonal influenza also occasionally results in neurologic complications. Rarely, viruses that have spread from wild birds to domestic poultry can infect humans; such “avian influenza” can range in severity from mild conjunctivitis through the rapidly lethal disease seen in persons infected with the H5N1 virus that first emerged in Hong Kong in 1997. To develop effective therapies for this wide range of diseases, it is essential to have laboratory animal models that replicate the major features of illness in humans. This review describes models currently in use for elucidating influenza pathogenesis and evaluating new therapeutic agents.",,"Barnard, Dale L.",,,,
,PMC,Delivery to the lower respiratory tract is required for effective immunization with Newcastle disease virus-vectored vaccines intended for humans,http://dx.doi.org/10.1016/j.vaccine.2009.01.009,PMC2723768,,,"Newcastle disease virus (NDV), an avian virus, is being evaluated for the development of vectored human vaccines against emerging pathogens. Previous studies of NDV-vectored vaccines in a mouse model suggested their potency after delivery by injection or by the intranasal route. We compared the efficacy of various routes of delivery of NDV-vectored vaccines in a non-human primate model. While delivery of an NDV vectored vaccine by the combined intranasal/intratracheal route elicited protective immune responses, delivery by the subcutaneous route or the intranasal route alone elicited limited or no protective immune responses, suggesting the necessity for vaccine delivery to the lower respiratory tract. Furthermore, direct comparison of a vaccine based on an NDV mesogenic strain (NDV-BC) with a similarly designed NDV vector based on a modified lentogenic strain carrying a polybasic F cleavage site (NDV-VF) suggested that the two NDV strains were similar in immunogenicity and were equally protective.",,"['DiNapoli, Joshua M.', 'Ward, Jerrold M.', 'Cheng, Lily', 'Yang, Lijuan', 'Elankumaran, Subbiah', 'Murphy, Brian R.', 'Samal, Siba K.', 'Collins, Peter L.', 'Bukreyev, Alexander']",,,,
,PMC,Beyond Picomolar Affinities: Quantitative Aspects of Noncovalent and Covalent Binding of Drugs to Proteins,http://dx.doi.org/10.1021/jm800498e,PMC2646787,,,,,"['Smith, Adam J. T.', 'Zhang, Xiyun', 'Leach, Andrew G.', 'Houk, K. N.']",,,,
,PMC,The promises and pitfalls of RNA-interference-based therapeutics,http://dx.doi.org/10.1038/nature07758,PMC2702667,,,"The discovery that gene expression can be controlled by the Watson–Crick base-pairing of small RNAs with messenger RNAs containing complementary sequence — a process known as RNA interference — has markedly advanced our understanding of eukaryotic gene regulation and function. The ability of short RNA sequences to modulate gene expression has provided a powerful tool with which to study gene function and is set to revolutionize the treatment of disease. Remarkably, despite being just one decade from its discovery, the phenomenon is already being used therapeutically in human clinical trials, and biotechnology companies that focus on RNA-interference-based therapeutics are already publicly traded.",,"['Castanotto, Daniela', 'Rossi, John J.']",,,,
,PMC,"Epidemiologic Study of Influenza Infection in Okinawa, Japan, from 2001 to 2007: Changing Patterns of Seasonality and Prevalence of Amantadine-Resistant Influenza A Virus",http://dx.doi.org/10.1128/JCM.01760-08,PMC2650946,,,"To clarify seasonal influenza patterns and the prevalence of amantadine-resistant influenza A viruses in Okinawa, located at the southern extremity of Japan in a subtropical climate, we conducted a laboratory-based study of influenza virus infections from 2001 to 2007. The annual outbreaks tended to show two peaks in Okinawa, in summer and winter, although the main islands of Japan, located in a temperate climate area, showed only winter influenza activity. Epidemic types and subtypes in Okinawa mostly matched those on the main islands of Japan in winter and those in Taiwan in summer. Rates of amantadine resistance dramatically increased, from 7.3% in the November 2002-to-March 2003 season to 90.0% in summer 2005, and a similarly high rate of resistance continued for the rest of the study period. Phylogenetic analysis of the hemagglutinin gene of A/H3N2 isolates collected from 2002 to 2007 revealed a monophyletic lineage that was divided into four period groups. Each group included amantadine-sensitive and -resistant viruses within independent clusters. In the November 2005-to-March 2006 season, all of the amantadine-resistant viruses were clustered in clade N, with dual (position 193 and 225) amino acid mutations in their HA1 subunits. In 2005, clade N amantadine-resistant viruses existed in Okinawa several months before the circulation of this clade on the main islands of Japan. In conclusion, surveillance in Okinawa to monitor influenza virus circulation is important for elucidating the dynamics of virus transmission in a border area between temperate and subtropical areas, as Okinawa is one of the best sentinel points in Japan.",,"['Suzuki, Yasushi', 'Taira, Katsuya', 'Saito, Reiko', 'Nidaira, Minoru', 'Okano, Shou', 'Zaraket, Hassan', 'Suzuki, Hiroshi']",,,,
,PMC,Comparison of Automated Microarray Detection with Real-Time PCR Assays for Detection of Respiratory Viruses in Specimens Obtained from Children,http://dx.doi.org/10.1128/JCM.01297-08,PMC2650908,,,"Respiratory virus infections are a major health concern and represent the primary cause of testing consultation and hospitalization for young children. We developed and compared two assays that allow the detection of up to 23 different respiratory viruses that frequently infect children. The first method consisted of single TaqMan quantitative real-time PCR assays in a 96-well-plate format. The second consisted of a multiplex PCR followed by primer extension and microarray hybridization in an integrated molecular diagnostic device, the Infiniti analyzer. Both of our assays can detect adenoviruses of groups A, B, C, and E; coronaviruses HKU1, 229E, NL63, and OC43; enteroviruses A, B, C, and D; rhinoviruses of genotypes A and B; influenza viruses A and B; human metapneumoviruses (HMPV) A and B, human respiratory syncytial viruses (HRSV) A and B; and parainfluenza viruses of types 1, 2, and 3. These tests were used to identify viruses in 221 nasopharyngeal aspirates obtained from children hospitalized for respiratory tract infections. Respiratory viruses were detected with at least one of the two methods in 81.4% of the 221 specimens: 10.0% were positive for HRSV A, 38.0% for HRSV B, 13.1% for influenzavirus A, 8.6% for any coronaviruses, 13.1% for rhinoviruses or enteroviruses, 7.2% for adenoviruses, 4.1% for HMPV, and 1.5% for parainfluenzaviruses. Multiple viral infections were found in 13.1% of the specimens. The two methods yielded concordant results for 94.1% of specimens. These tests allowed a thorough etiological assessment of respiratory viruses infecting children in hospital settings and would assist public health interventions.",,"['Raymond, Frédéric', 'Carbonneau, Julie', 'Boucher, Nancy', 'Robitaille, Lynda', 'Boisvert, Sébastien', 'Wu, Whei-Kuo', 'De Serres, Gaston', 'Boivin, Guy', 'Corbeil, Jacques']",,,,
,PMC,Development of a Novel Transgenic Rat Overexpressing the P2Y(2) Nucleotide Receptor Using a Lentiviral Vector,http://dx.doi.org/10.1159/000194274,PMC3593343,,,"The G protein-coupled P2Y(2) nucleotide receptor (P2Y(2)R) is upregulated in response to stress and tissue injury and has been postulated to play a role in chronic inflammation seen in atherosclerosis, Alzheimer’s disease and Sjögren’s syndrome. The role of P2Y(2)R upregulation in vivo is poorly understood, in part due to the lack of a P2Y(2)R overexpressing animal model. The P2Y(2)R overexpressing transgenic rat was generated using a lentiviral vector. Rats overexpressing P2Y(2)R showed a significant increase in P2Y(2)R mRNA levels in all tissues screened as compared to nontransgenic rats. Fura 2 imaging of smooth muscle cells (SMCs) isolated from aorta indicated that the percentage of cells exhibiting increases in the intracellular free calcium concentration in response to P2Y(2)R agonists was significantly greater in freshly isolated SMCs from transgenic rats than wild-type controls. Histopathological examination of tissues revealed that P2Y(2)R overexpressing rats develop lymphocytic infiltration in lacrimal glands and kidneys as early as at 3 months of age. These rats show similarities to patients with Sjögren’s syndrome who display lymphocyte-mediated tissue damage. This transgenic rat model of P2Y(2)R overexpression may prove useful for linking P2Y(2)R upregulation with chronic inflammatory diseases, neurodegenerative diseases and Sjögren’s syndrome.",,"['Agca, Cansu', 'Seye, Cheikh', 'Benson, Corinna M. Kashuba', 'Rikka, Shivaji', 'Chan, Anthony W.S.', 'Weisman, Gary A.', 'Agca, Yuksel']",,,,
,PMC,Proteolytic Activation of the 1918 Influenza Virus Hemagglutinin,http://dx.doi.org/10.1128/JVI.02205-08,PMC2655587,,,"Proteolytic activation of the hemagglutinin (HA) protein is indispensable for influenza virus infectivity, and the tissue expression of the responsible cellular proteases impacts viral tropism and pathogenicity. The HA protein critically contributes to the exceptionally high pathogenicity of the 1918 influenza virus, but the mechanisms underlying cleavage activation of the 1918 HA have not been characterized. The neuraminidase (NA) protein of the 1918 influenza virus allows trypsin-independent growth in canine kidney cells (MDCK). However, it is at present unknown if the 1918 NA, like the NA of the closely related strain A/WSN/33, facilitates HA cleavage activation by recruiting the proprotease plasminogen. Moreover, it is not known which pulmonary proteases activate the 1918 HA. We provide evidence that NA-dependent, trypsin-independent cleavage activation of the 1918 HA is cell line dependent and most likely plasminogen independent since the 1918 NA failed to recruit plasminogen and neither exogenous plasminogen nor the presence of the A/WSN/33 NA promoted efficient cleavage of the 1918 HA. The transmembrane serine protease TMPRSS4 was found to be expressed in lung tissue and was shown to cleave the 1918 HA. Accordingly, coexpression of the 1918 HA with TMPRSS4 or the previously identified HA-processing protease TMPRSS2 allowed trypsin-independent infection by pseuodotypes bearing the 1918 HA, indicating that these proteases might support 1918 influenza virus spread in the lung. In summary, we show that the previously reported 1918 NA-dependent spread of the 1918 influenza virus is a cell line-dependent phenomenon and is not due to plasminogen recruitment by the 1918 NA. Moreover, we provide evidence that TMPRSS2 and TMPRSS4 activate the 1918 HA by cleavage and therefore may promote viral spread in lung tissue.",,"['Chaipan, Chawaree', 'Kobasa, Darwyn', 'Bertram, Stephanie', 'Glowacka, Ilona', 'Steffen, Imke', 'Solomon Tsegaye, Theodros', 'Takeda, Makoto', 'Bugge, Thomas H.', 'Kim, Semi', 'Park, Youngwoo', 'Marzi, Andrea', 'Pöhlmann, Stefan']",,,,
,PMC,Bridging the divide: global governance of trade and health,http://dx.doi.org/10.1016/S0140-6736(08)61776-6,PMC2730441,,,"The main institutions responsible for governing international trade and health—the World Trade Organization (WTO), which replaced the General Agreement on Tariffs and Trade (GATT) in 1995, and WHO—were established after World War 2. For many decades the two institutions operated in isolation, with little cooperation between them. The growth and expansion of world trade over the past half century amid economic globalisation, and the increased importance of health issues to the functioning of a more interconnected world, brings the two domains closer together on a broad range of issues. Foremost is the capacity of each to govern their respective domains, and their ability to cooperate in tackling issues that lie at the intersection of trade and health. This paper discusses how the governance of these two areas relate to one another, and how well existing institutions work together.",,"['Lee, Kelley', 'Sridhar, Devi', 'Patel, Mayur']",,,,
,PMC,The Polyomaviridae: Contributions of virus structure to our understanding of virus receptors and infectious entry,http://dx.doi.org/10.1016/j.virol.2008.12.021,PMC2663363,,,"This review summarizes the fields major findings related to the characterization of polyomavirus structures and to the characterization of virus receptors and mechanisms of host cell invasion. Four members of the family that have received the most attention in this regard are the mouse polyomavirus (mPyV), the monkey polyomavirus SV40, and the two human polyomaviruses, JCV and BKV. The structures of both the mPyV and SV40 alone and in complex with receptor fragments have been solved to high resolution. The majority of polyomaviruses recognize terminal sialic acid in either an α 2,3 linkage or an α 2,6 linkage to the underlying galactose. Studies on virus structure, receptor utilization and mechanisms of entry have led to new insights into how these viruses interact in an active way with cells to ensure the nuclear delivery and expression of their genomes. Critical work on virus entry has led to the discovery of a pH neutral endocytic compartment that accepts cargo from caveolae and to novel roles for endoplasmic reticulum (ER) associated factors in virus uncoating and penetration of ER membranes. This review will summarize the major findings and compare and contrast the mechanisms used by these viruses to infect cells.",,"['Neu, Ursula', 'Stehle, Thilo', 'Atwood, Walter J.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus nsp9 Dimerization Is Essential for Efficient Viral Growth,http://dx.doi.org/10.1128/JVI.01505-08,PMC2655571,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) devotes a significant portion of its genome to producing nonstructural proteins required for viral replication. SARS-CoV nonstructural protein 9 (nsp9) was identified as an essential protein with RNA/DNA-binding activity, and yet its biological function within the replication complex remains unknown. Nsp9 forms a dimer through the interaction of parallel α-helices containing the protein-protein interaction motif GXXXG. In order to study the role of the nsp9 dimer in viral reproduction, residues G100 and G104 at the helix interface were targeted for mutation. Multi-angle light scattering measurements indicated that G100E, G104E, and G104V mutants are monomeric in solution, thereby disrupting the dimer. However, electrophoretic mobility assays revealed that the mutants bound RNA with similar affinity. Further experiments using fluorescence anisotropy showed a 10-fold reduction in RNA binding in the G100E and G104E mutants, whereas the G104V mutant had only a 4-fold reduction. The structure of G104E nsp9 was determined to 2.6-Å resolution, revealing significant changes at the dimer interface. The nsp9 mutations were introduced into SARS-CoV using a reverse genetics approach, and the G100E and G104E mutations were found to be lethal to the virus. The G104V mutant produced highly debilitated virus and eventually reverted back to the wild-type protein sequence through a codon transversion. Together, these data indicate that dimerization of SARS-CoV nsp9 at the GXXXG motif is not critical for RNA binding but is necessary for viral replication.",,"['Miknis, Zachary J.', 'Donaldson, Eric F.', 'Umland, Timothy C.', 'Rimmer, Ryan A.', 'Baric, Ralph S.', 'Schultz, L. Wayne']",,,,
,PMC,A cysteine-rich metal-binding domain from rubella virus non-structural protein is essential for viral protease activity and virus replication,http://dx.doi.org/10.1042/BJ20081468,PMC2908387,,,"The protease domain within the RUBV (rubella virus) NS (non-structural) replicase proteins functions in the self-cleavage of the polyprotein precursor into the two mature proteins which form the replication complex. This domain has previously been shown to require both zinc and calcium ions for optimal activity. In the present study we carried out metal-binding and conformational experiments on a purified cysteine-rich minidomain of the RUBV NS protease containing the putative Zn(2+)-binding ligands. This minidomain bound to Zn(2+) with a stoichiometry of ≈0.7 and an apparent dissociation constant of < 500 nM. Fluorescence quenching and 8-anilinonaphthalene-1-sulfonic acid fluorescence methods revealed that Zn(2+) binding resulted in conformational changes characterized by shielding of hydrophobic regions from the solvent. Mutational analyses using the minidomain identified residues Cys(1175), Cys(1178), Cys(1225) and Cys(1227) were required for the binding of Zn(2+). Corresponding mutational analyses using a RUBV replicon confirmed that these residues were necessary for both proteolytic activity of the NS protease and viability. The present study demonstrates that the CXXC(X)(48)CXC Zn(2+)-binding motif in the RUBV NS protease is critical for maintaining the structural integrity of the protease domain and essential for proteolysis and virus replication.",,"['ZHOU, Yubin', 'TZENG, Wen-Pin', 'YE, Yiming', 'HUANG, Yun', 'LI, Shunyi', 'CHEN, Yanyi', 'FREY, Teryl K.', 'YANG, Jenny J.']",,,,
,PMC,Hepatitis C virus association with peripheral blood B lymphocytes potentiates viral infection of liver-derived hepatoma cells,http://dx.doi.org/10.1182/blood-2008-05-158824,PMC2628366,,,"Hepatitis C virus (HCV) primarily replicates within the liver, leading to hepatitis, fibrosis, and hepatocellular carcinoma. Infection is also associated with B-cell abnormalities, suggesting an association of the virus with B cells. The infectious JFH-1 strain of HCV can bind primary and immortalized B cells but fails to establish productive infection. However, B cell–associated virus readily infects hepatoma cells, showing an enhanced infectivity compared with extracellular virus. B cells express the viral receptors CD81, SR-BI, and the C-type lectins DC-SIGN and L-SIGN. Antibodies specific for SR-BI and DC-SIGN/L-SIGN reduced B-cell transinfection, supporting a role for these molecules in B-cell association with HCV. Stimulation of B cells with CD40 ligand and interleukin-4 promoted their ability to transinfect hepatoma cells. B cell–associated virus is resistant to trypsin proteolysis and HCV-specific neutralizing antibodies, consistent with particle internalization. HCV promoted the adhesion of primary B cells to Huh-7 hepatomas, providing a mechanism for B-cell retention in the infected liver. In summary, B cells may provide a vehicle for HCV to persist and transmit to the liver.",,"['Stamataki, Zania', 'Shannon-Lowe, Claire', 'Shaw, Jean', 'Mutimer, David', 'Rickinson, Alan B.', 'Gordon, John', 'Adams, David H.', 'Balfe, Peter', 'McKeating, Jane A.']",,,,
,PMC,Tannic acid facilitates expression of the polypyrimidine tract binding protein and alleviates deleterious inclusion of CHRNA1 exon P3A due to an hnRNP H-disrupting mutation in congenital myasthenic syndrome,http://dx.doi.org/10.1093/hmg/ddp023,PMC2655771,,,"We recently reported that the intronic splice-site mutation IVS3-8G>A of CHRNA1 that encodes the muscle nicotinic acetylcholine receptor α subunit disrupts binding of a splicing repressor, hnRNP H. This, in turn, results in exclusive inclusion of the downstream exon P3A. The P3A(+) transcript encodes a non-functional α subunit that comprises 50% of the transcripts in normal human skeletal muscle, but its functional significance remains undetermined. In an effort to search for a potential therapy, we screened off-label effects of 960 bioactive chemical compounds and found that tannic acid ameliorates the aberrant splicing due to IVS3-8G>A but without altering the expression of hnRNP H. Therefore, we searched for another splicing trans-factor. We found that the polypyrimidine tract binding protein (PTB) binds close to the 3′ end of CHRNA1 intron 3, that PTB induces skipping of exon P3A and that tannic acid increases the expression of PTB in a dose-dependent manner. Deletion assays of the PTB promoter region revealed that the tannic acid-responsive element is between positions −232 and −74 from the translation initiation site. These observations open the door to the discovery of novel therapies based on PTB overexpression and to detecting possible untoward effects of the overexpression.",,"['Bian, Yang', 'Masuda, Akio', 'Matsuura, Tohru', 'Ito, Mikako', 'Okushin, Kazuya', 'Engel, Andrew G.', 'Ohno, Kinji']",,,,
,PMC,A new bocavirus species in human stool,http://dx.doi.org/10.1086/595831,PMC2678954,,,"Using viral metagenomics we identified a novel parvovirus species in human stool whose closest phylogenetic relative is the human bocavirus (HBoV). HBoV2 has an identical genomic organization to HBoV but share only 78%, 67%, and 80% identity to its NS1, NP1 and VP1/VP2 proteins. Using PCR we detected HBoV2 sequences in 5/98 Pakistani children stool samples and 3/699 stool samples from the UK. Near full genome sequencing showed the presence of three divergent genotypes and evidence of recombination. Further studies are required to determine sites of replication of HBoV2 and potential associations with clinical symptoms or disease.",,"['Kapoor, Amit', 'Slikas, Elizabeth', 'Simmonds, Peter', 'Chieochansin, Thaweesak', 'Naeem, Asif', 'Shaukat, Shahzad', 'Alam, Muhammad Masroor', 'Sharif, Salmaan', 'Angez, Mehar', 'Zaidi, Sohail', 'Delwart, Eric']",,,,
,PMC,Acute Rejection and Humoral Sensitization in Lung Transplant Recipients,http://dx.doi.org/10.1513/pats.200808-080GO,PMC2626504,,,"Despite the recent introduction of many improved immunosuppressive agents for use in transplantation, acute rejection affects up to 55% of lung transplant recipients within the first year after transplant. Acute lung allograft rejection is defined as perivascular or peribronchiolar mononuclear inflammation. Although histopathologic signs of rejection often resolve with treatment, the frequency and severity of acute rejections represent the most important risk factor for the subsequent development of bronchiolitis obliterans syndrome (BOS), a condition of progressive airflow obstruction that limits survival to only 50% at 5 years after lung transplantation. Recent evidence demonstrates that peribronchiolar mononuclear inflammation (also known as lymphocytic bronchiolitis) or even a single episode of minimal perivascular inflammation significantly increase the risk for BOS. We comprehensively review the clinical presentation, diagnosis, histopathologic features, and mechanisms of acute cellular lung rejection. In addition, we consider emerging evidence that humoral rejection occurs in lung transplantation, characterized by local complement activation or the presence of antibody to donor human leukocyte antigens (HLA). We discuss in detail methods for HLA antibody detection as well as the clinical relevance, the mechanisms, and the pathologic hallmarks of humoral injury. Treatment options for cellular rejection include high-dose methylprednisolone, antithymocyte globulin, or alemtuzumab. Treatment options for humoral rejection include intravenous immunoglobulin, plasmapheresis, or rituximab. A greater mechanistic understanding of cellular and humoral forms of rejection and their role in the pathogenesis of BOS is critical in developing therapies that extend long-term survival after lung transplantation.",,"['Martinu, Tereza', 'Chen, Dong-Feng', 'Palmer, Scott M.']",,,,
,PMC,Pathogenesis of 1918 Pandemic and H5N1 Influenza Virus Infections in a Guinea Pig Model: Antiviral Potential of Exogenous Alpha Interferon To Reduce Virus Shedding,http://dx.doi.org/10.1128/JVI.02174-08,PMC2655560,,,"Although highly pathogenic avian influenza H5N1 viruses have yet to acquire the ability to transmit efficiently among humans, the increasing genetic diversity among these viruses and continued outbreaks in avian species underscore the need for more effective measures for the control and prevention of human H5N1 virus infection. Additional small animal models with which therapeutic approaches against virulent influenza viruses can be evaluated are needed. In this study, we used the guinea pig model to evaluate the relative virulence of selected avian and human influenza A viruses. We demonstrate that guinea pigs can be infected with avian and human influenza viruses, resulting in high titers of virus shedding in nasal washes for up to 5 days postinoculation (p.i.) and in lung tissue of inoculated animals. However, other physiologic indicators typically associated with virulent influenza virus strains were absent in this species. We evaluated the ability of intranasal treatment with human alpha interferon (α-IFN) to reduce lung and nasal wash titers in guinea pigs challenged with the reconstructed 1918 pandemic H1N1 virus or a contemporary H5N1 virus. IFN treatment initiated 1 day prior to challenge significantly reduced or prevented infection of guinea pigs by both viruses, as measured by virus titer determination and seroconversion. The expression of the antiviral Mx protein in lung tissue correlated with the reduction of virus titers. We propose that the guinea pig may serve as a useful small animal model for testing the efficacy of antiviral compounds and that α-IFN treatment may be a useful antiviral strategy against highly virulent strains with pandemic potential.",,"['Van Hoeven, Neal', 'Belser, Jessica A.', 'Szretter, Kristy J.', 'Zeng, Hui', 'Staeheli, Peter', 'Swayne, David E.', 'Katz, Jacqueline M.', 'Tumpey, Terrence M.']",,,,
,PMC,In This Issue,http://dx.doi.org/10.1073/iti0209106,PMC2626704,,,,,,,,,
,PMC,Impact of spatial clustering on disease transmission and optimal control,http://dx.doi.org/10.1073/pnas.0909047107,PMC2824282,,,"Spatial heterogeneities and spatial separation of hosts are often seen as key factors when developing accurate predictive models of the spread of pathogens. The question we address in this paper is how coarse the resolution of the spatial data can be for a model to be a useful tool for informing control policies. We examine this problem using the specific case of foot-and-mouth disease spreading between farms using the formulation developed during the 2001 epidemic in the United Kingdom. We show that, if our model is carefully parameterized to match epidemic behavior, then using aggregate county-scale data from the United States is sufficient to closely determine optimal control measures (specifically ring culling). This result also holds when the approach is extended to theoretical distributions of farms where the spatial clustering can be manipulated to extremes. We have therefore shown that, although spatial structure can be critically important in allowing us to predict the emergent population-scale behavior from a knowledge of the individual-level dynamics, for this specific applied question, such structure is mostly subsumed in the parameterization allowing us to make policy predictions in the absence of high-quality spatial information. We believe that this approach will be of considerable benefit across a range of disciplines where data are only available at intermediate spatial scales.",,"['Tildesley, Michael J.', 'House, Thomas A.', 'Bruhn, Mark C.', 'Curry, Ross J.', 'O’Neil, Maggie', 'Allpress, Justine L. E.', 'Smith, Gary', 'Keeling, Matt J.']",,,,
,PMC,Structural plasticity of the phage P22 tail needle gp26 probed with xenon gas,http://dx.doi.org/10.1002/pro.53,PMC2760360,,,"The tail needle, gp26, is a highly stable homo-trimeric fiber found in the tail apparatus of bacteriophage P22. In the mature virion, gp26 is responsible for plugging the DNA exit channel, and likely plays an important role in penetrating the host cell envelope. In this article, we have determined the 1.98 Å resolution crystal structure of gp26 bound to xenon gas. The structure led us to identify a calcium and a chloride ion intimately bound at the interior of α-helical core, as well as seven small cavities occupied by xenon atoms. The two ions engage in buried polar interactions with gp26 side chains that provide specificity and register to gp26 helical core, thus enhancing its stability. Conversely, the distribution of xenon accessible cavities correlates well with the flexibility of the fiber observed in solution and in the crystal structure. We suggest that small internal cavities in gp26 between the helical core and the C-terminal tip allow for flexible swinging of the latter, without affecting the overall stability of the protein. The C-terminal tip may be important in scanning the bacterial surface in search of a cell-envelope penetration site, or for recognition of a yet unidentified receptor on the surface of the host.",,"['Olia, Adam S', 'Casjens, Sherwood', 'Cingolani, Gino']",,,,
,PMC,The strong dimerization of the transmembrane domain of the fibroblast growth factor receptor (FGFR) is modulated by C-terminal juxtamembrane residues,http://dx.doi.org/10.1002/pro.65,PMC2708062,,,"The fibroblast growth factor receptor 3 (FGFR3) is a member of the FGFR subfamily of the receptor tyrosine kinases (RTKs) involved in signaling across the plasma membrane. Generally, ligand binding leads to receptor dimerization and activation. Dimerization involves the transmembrane (TM) domain, where mutations can lead to constitutive activation in certain cancer types and also in skeletal malformations. Thus, it has been postulated that FGFR homodimerization must be inherently weak to allow regulation, a feature reminiscent of α and β integrin TM interactions. However, we show herein that in FGFR3-TM, four C-terminal residues, CRLR, have a profound destabilizing effect in an otherwise strongly dimerizing TM peptide. In the absence of these four residues, the dimerizing propensity of FGFR3-TM is comparable to glycophorin, as shown using various detergents. In addition, the expected enhanced dimerization induced by the mutation associated to the Crouzon syndrome A391E, was observed only when these four C-terminal residues were present. In the absence of these four residues, A391E was dimer-destabilizing. Finally, using site specific infrared dichroism and convergence with evolutionary conservation data, we have determined the backbone model of the FGFR3-TM homodimer in model lipid bilayers. This model is consistent with, and correlates with the effects of, most known pathological mutations found in FGFR-TM.",,"['Peng, Weng Chuan', 'Lin, Xin', 'Torres, Jaume']",,,,
,PMC,Role of Regulatory T Cells in Coronavirus-Induced Acute Encephalitis,http://dx.doi.org/10.1016/j.virol.2008.12.014,PMC2684864,,,"C57BL/6 mice infected with mouse hepatitis virus, strain JHM (JHMV) develop a rapidly fatal acute encephalitis. Previously, we showed that this disease is partially CD4 T cell-mediated since infection with a recombinant JHMV (rJ) mutated in only a single immunodominant CD4 T cell epitope (epitope M133, rJ.M(Y135Q)) results in a nonlethal disease. Increased mortality correlated with a greater number of JHMV-specific CD4 T cells in the brains of rJ compared to rJ.M(Y135Q)-infected mice. Here, we extend these results to show that the diminished number of virus-specific T cells correlates with a reduced cytokine/chemokine response in the infected brain. We also show that regulatory CD4 T cells (Tregs) are critical for mild disease in rJ.M(Y135Q)-infected mice because their depletion results in increased mortality. Further, a relative paucity of Tregs characterizes lethal infection because adoptive transfer of Tregs into rJ-infected mice increases survival from 0% to 50%. These results support the notion that clinical disease in coronavirus-induced acute encephalitis results from a balance between factors critical for virus clearance, such as virus-specific effector T cells and anti-inflammatory elements, such as Tregs. These findings also show that unlike chronic infections, in which an excessive number of Tregs contributes to pathogen persistence, Tregs in the setting of acute encephalitis may help to limit immunopathological disease without delaying virus clearance.",,"['Anghelina, Daniela', 'Zhao, Jingxian', 'Trandem, Kathryn', 'Perlman, Stanley']",,,,
,PMC,"Agonist and Antagonist Recognition by RIG-I, a Cytoplasmic Innate  Immunity  Receptor",http://dx.doi.org/10.1074/jbc.M806219200,PMC2613625,,,"Cytoplasmic RNA receptors are important in the detection of and response to viral infections. We analyzed ligand recognition by the retinoic acid-inducible protein I (RIG-I) protein in biochemical assays and in transiently transfected cells and characterized the requirements for both single- and double-stranded RNA agonists for RIG-I activation of signaling. RIG-I mutants such as K270A and T409A/S411A that were defective in signaling with triphosphorylated single-stranded RNAs were perfectly capable of signaling with dsRNAs. Furthermore, phosphorothioated oligodeoxynucleotides were found to antagonize RIG-I signaling. Both agonists and antagonist bind purified RIG-I protein and a truncated RIG-I protein that lacked the signaling domain. The agonists were necessary to activate RIG-I ATPase activity in vitro, whereas antagonist inhibited ATPase activity. Differential scanning fluorometry showed that RIG-I bound to agonists, and antagonists have different denaturation properties, suggesting a difference in protein conformations. Last, single particle reconstruction was used to generate three-dimensional models of the RIG-I dimers in complex with an agonist and an antagonist. The two complexes exhibited dramatically different structures.",,"['Ranjith-Kumar, C. T.', 'Murali, Ayaluru', 'Dong, Wen', 'Srisathiyanarayanan, Dharmaiah', 'Vaughan, Robert', 'Ortiz-Alacantara, Joanna', 'Bhardwaj, Kanchan', 'Li, Xiaojun', 'Li, Pingwei', 'Kao, Cheng C.']",,,,
,PMC,"Biochemical and biophysical comparison of cleaved and uncleaved soluble, trimeric HIV-1 envelope glycoproteins",http://dx.doi.org/10.1016/j.virol.2008.12.009,PMC3795524,,,"Human immunodeficiency virus type 1 (HIV-1) entry into host cells is mediated by the trimeric envelope glycoprotein complex (Env). Accordingly, the Env proteins are the targets for neutralizing antibodies (NAbs) and are the focus of vaccines intended to induce NAbs. Because the Env complex is labile, soluble recombinant Env (gp140) trimers require engineering to stabilize them sufficiently for use as immunogens. Trimeric forms of gp140 trimers can be created that are either cleavage-competent or cleavage-defective at the junction between the gp120 and gp41 subunits. As functional trimers are cleaved at this site, the question arises as to whether cleavage affects the antigenic structure of the Env complex in a way that is relevant to vaccine design. Here, we present a comparative analysis of the antigenicity profiles of cleaved and uncleaved gp140 trimers derived from the KNH1144 (subtype A) virus that are otherwise closely sequence-matched. While cleavage did not affect the exposure of NAb epitopes on the gp140 trimers, non-neutralizing antibodies to gp41 epitopes bound much more strongly to uncleaved trimers. Hence cleavage does alter the structure of the HIV-1 Env complex.",,"['Dey, Antu K.', 'David, Kathryn B.', 'Lu, Min', 'Moore, John P.']",,,,
,PMC,Translation Elongation Factor 1A is a component of the tombusvirus replicase complex and affects the stability of the p33 replication co-factor,http://dx.doi.org/10.1016/j.virol.2008.11.041,PMC2785496,,,"Host RNA-binding proteins are likely to play multiple, integral roles during replication of plus-strand RNA viruses. To identify host proteins that bind to viral RNAs, we took a global approach based on the yeast proteome microarray, which contains 4080 purified yeast proteins. The biotin-labeled RNA probes included two distantly related RNA viruses, namely Tomato bushy stunt virus (TBSV) and Brome mosaic virus (BMV). Altogether, we have identified 57 yeast proteins that bound to TBSV RNA and/or BMV RNA. Among the identified host proteins, eleven bound to TBSV RNA and seven bound to BMV RNA with high selectivity, whereas the remaining 39 host proteins bound to both viral RNAs. The interaction between the TBSV replicon RNA and five of the identified host proteins were confirmed via gel-mobility shift and co-purification experiments from yeast. Over-expression of the host proteins in yeast, a model host for TBSV, revealed that 4 host proteins that enhanced TBSV replication as well as 14 proteins that inhibited replication. Detailed analysis of one of the identified yeast proteins binding to TBSV RNA, namely translation elongation factor eEF1A, revealed that it is present in the highly purified tombusvirus replicase complex. We also demonstrate binding of eEF1A to the p33 replication protein and a known cis-acting element at the 3′ end of TBSV RNA. Using a functional mutant of eEF1A, we provide evidence on the involvement of eEF1A in TBSV replication.",,"['Li, Zhenghe', 'Pogany, Judit', 'Panavas, Tadas', 'Xu, Kai', 'Esposito, Anthony M.', 'Kinzy, Terri Gross', 'Nagy, Peter D.']",,,,
,PMC,Contact heterogeneity in deer mice: implications for Sin Nombre virus transmission,http://dx.doi.org/10.1098/rspb.2008.1693,PMC2660967,,,"Heterogeneities within disease hosts suggest that not all individuals have the same probability of transmitting disease or becoming infected. This heterogeneity is thought to be due to dissimilarity in susceptibility and exposure among hosts. As such, it has been proposed that many host–pathogen systems follow the general pattern whereby a small fraction of the population accounts for a large fraction of the pathogen transmission. This disparity in transmission dynamics is often referred to as ‘20/80 Rule’, i.e. approximately 20 per cent of the hosts are responsible for 80 per cent of pathogen transmission. We investigated the role of heterogeneity in contact rates among potential hosts of a directly transmitted pathogen by examining Sin Nombre virus (SNV) in deer mice (Peromyscus maniculatus). Using foraging arenas and powder marking, we documented contacts between wild deer mice in Great Basin Desert, central Utah. Our findings demonstrated heterogeneity among deer mice, both in frequency and in duration of contacts with other deer mice. Contact dynamics appear to follow the general pattern that a minority of the population accounts for a majority of the contacts. We found that 20 per cent of individuals in the population were responsible for roughly 80 per cent of the contacts observed. Larger-bodied individuals appear to be the functional group with the greatest SNV transmission potential. Contrary to our predictions, transmission potential was not influenced by breeding condition or sex.",,"['Clay, Christine A.', 'Lehmer, Erin M.', 'Previtali, Andrea', 'St. Jeor, Stephen', 'Dearing, M. Denise']",,,,
,PMC,Cryo-electron tomography of mouse hepatitis virus: Insights into the structure of the coronavirion,http://dx.doi.org/10.1073/pnas.0805270106,PMC2613939,,,"Coronaviruses are enveloped viruses containing the largest reported RNA genomes. As a result of their pleomorphic nature, our structural insight into the coronavirion is still rudimentary, and it is based mainly on 2D electron microscopy. Here we report the 3D virion structure of coronaviruses obtained by cryo-electron tomography. Our study focused primarily on the coronavirus prototype murine hepatitis virus (MHV). MHV particles have a distinctly spherical shape and a relatively homogenous size (≈85 nm envelope diameter). The viral envelope exhibits an unusual thickness (7.8 ± 0.7 nm), almost twice that of a typical biological membrane. Focal pairs revealed the existence of an extra internal layer, most likely formed by the C-terminal domains of the major envelope protein M. In the interior of the particles, coiled structures and tubular shapes are observed, consistent with a helical nucleocapsid model. Our reconstructions provide no evidence of a shelled core. Instead, the ribonucleoprotein seems to be extensively folded onto itself, assuming a compact structure that tends to closely follow the envelope at a distance of ≈4 nm. Focal contact points and thread-like densities connecting the envelope and the ribonucleoprotein are revealed in the tomograms. Transmissible gastroenteritis coronavirion tomograms confirm all the general features and global architecture observed for MHV. We propose a general model for the structure of the coronavirion in which our own and published observations are combined.",,"['Bárcena, Montserrat', 'Oostergetel, Gert T.', 'Bartelink, Willem', 'Faas, Frank G. A.', 'Verkleij, Arie', 'Rottier, Peter J. M.', 'Koster, Abraham J.', 'Bosch, Berend Jan']",,,,
,PMC,Regulation and Cellular Roles of Ubiquitin-specific Deubiquitinating Enzymes,http://dx.doi.org/10.1146/annurev.biochem.78.082307.091526,PMC2734102,,,"Deubiquitinating enzymes (DUBs) are proteases that process ubiquitin or ubiquitin-like gene products, reverse the modification of proteins by a single ubiquitin (or ubiquitin-like protein), and remodel polyubiquitin (or ubiquitin-like) chains on target proteins. The human genome encodes nearly 100 DUBs with specificity for ubiquitin in five families: the UCH, USP, OTU, Josephin, and JAMM families. Four families are cysteine proteases, while the later is a family of metalloproteases. Most DUB activity is cryptic and active site rearrangements often occur during the binding of ubiquitin and/or scaffold proteins. DUBs with specificity for ubiquitin contain multiple domains with insertions and extensions modulating DUB substrate specificity, protein-protein interactions, and cellular localization. Binding partners and multi-protein complexes with which DUBs associate modulate DUB activity and substrate specificity. Quantitative studies of activity and protein-protein interactions, together with genetic studies and the advent of RNAi, have lead to new insights into the function of yeast and human DUBs. This review will discuss ubiquitin-specific DUBs, some of the generalizations emerging from recent studies of the regulation of DUB activity, and their roles in various cellular processes. Specific examples are drawn from studies of protein degradation, DNA repair, chromatin remodeling, cell cycle regulation, endocytosis, and modulation of signaling kinases.",,"['Turcu, Francisca E. Reyes', 'Ventii, Karen H.', 'Wilkinson, Keith D.']",,,,
,PMC,Progress on the induction of neutralizing antibodies against HIV-1,http://dx.doi.org/10.2165/00063030-200923030-00001,PMC3764985,,,"The Human Immunodeficiency Virus Type -1 (HIV-1), the causative agent of AIDS in humans, is one of the most catastrophic pandemics to affect human health care in the latter 20(th) century. The best hope of controlling this pandemic is the development of a successful prophylactic vaccine. However, to date, this goal has proven to be exceptionally elusive. The recent failure of an experimental AIDS vaccine in a phase IIb study named the STEP trial, intended to solely elicit cell mediated immune responses against HIV-1, has highlighted the need for a balanced immune response consisting of not only cellular immunity but also a broad and potent antibody response which can prevent the infection of HIV-1. This article will review the efforts being made up to this point to elicit such antibody responses, especially with regards to the use of a DNA prime-protein boost regimen which has been proven to be a highly effective platform for the induction of neutralizing antibodies in both animal and early phase human studies.",,"['Vaine, Michael', 'Lu, Shan', 'Wang, Shixia']",,,,
,PMC,Infectious bronchitis virus in Jordanian chickens: Seroprevalence and detection,,PMC2603658,,,"Infectious bronchitis (IB) is one of the most important viral diseases of poultry; it causes major economic losses to the poultry industry. This study was conducted to investigate the prevalence of infectious bronchitis virus (IBV) in commercial chicken flocks in Jordan. Serum samples from 70 commercial chicken flocks (40 broilers, 18 layers, and 12 broiler breeders) free from respiratory disease were collected and screened for the presence of Massachusetts-41 (M-41), D274, and 4/91 strain antigens of IBV by using the hemagglutination inhibition (HI) test. In addition, 51 commercial chicken flocks (25 broilers, 15 layers, and 11 broiler breeders) suffering from respiratory disease were tested for the presence of IBV, using the reverse-transcription polymerase chain reaction. Overall, 92.9% of the flocks free from respiratory disease were seropositive for antibodies to the M-41 strain, whereas 90% and 61.4% of the flocks were seropositive for antibodies to the 4/91 and D274 strains, respectively. Infectious bronchitis virus nucleic acid was detected in 16 broiler (64%), 8 layer (53%), and 6 broiler breeder (54.54%) flocks affected with respiratory disease. This study clearly demonstrates that several strains of IBV are present in poultry flocks in Jordan. Future work should include the isolation and serotyping of IBV in the region, so that a suitable vaccination program, using the common field serotypes as vaccines, can be adopted to protect against IBV-caused disease. Furthermore, farmers need to be educated about the clinical signs of IB and the importance of IBV.",,"['Roussan, Dergham A.', 'Khawaldeh, Ghassan Y.', 'Shaheen, Ibrahem A.']",,,,
,PMC,Peptide Nanoparticles as Novel Immunogens: Design and Analysis of a Prototypic Severe Acute Respiratory Syndrome Vaccine,http://dx.doi.org/10.1111/j.1747-0285.2008.00746.x,PMC2756483,,,"Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel coronavirus that cost nearly 800 lives. While there have been no recent outbreaks of the disease, the threat remains as SARS coronavirus (SARS-CoV) like strains still exist in animal reservoirs. Therefore, the development of a vaccine against SARS is in grave need. Here, we have designed and produced a prototypic SARS vaccine: a self-assembling polypeptide nanoparticle that repetitively displays a SARS B-cell epitope from the C-terminal heptad repeat of the virus’ spike protein. Biophysical analyses with circular dichroism, transmission electron microscopy and dynamic light scattering confirmed the computational design showing α-helcial nanoparticles with sizes of about 25 nm. Immunization experiments with no adjuvants were performed with BALB/c mice. An investigation of the binding properties of the elicited antibodies showed that they were highly conformation specific for the coiled-coil epitope because they specifically recognized the native trimeric conformation of C-terminal heptad repeat region. Consequently, the antisera exhibited neutralization activity in an in vitro infection inhibition assay. We conclude that these peptide nanoparticles represent a promising platform for vaccine design, in particular for diseases that are characterized by neutralizing epitopes with coiled-coil conformation such as SARS-CoV or other enveloped viruses.",,"['Pimentel, Tais A. P. F.', 'Yan, Zhe', 'Jeffers, Scott A.', 'Holmes, Kathryn V.', 'Hodges, Robert S.', 'Burkhard, Peter']",,,,
,PMC,The role of infections in autoimmune disease,http://dx.doi.org/10.1111/j.1365-2249.2008.03834.x,PMC2665673,,,"Autoimmunity occurs when the immune system recognizes and attacks host tissue. In addition to genetic factors, environmental triggers (in particular viruses, bacteria and other infectious pathogens) are thought to play a major role in the development of autoimmune diseases. In this review, we (i) describe the ways in which an infectious agent can initiate or exacerbate autoimmunity; (ii) discuss the evidence linking certain infectious agents to autoimmune diseases in humans; and (iii) describe the animal models used to study the link between infection and autoimmunity.",,"['Ercolini, A M', 'Miller, S D']",,,,
,PMC,Cardiovascular Effects of Losartan and Its Relevant Clinical Application,,PMC2888651,,,"The renin-angiotensin system (RAS) plays an important role in the homeostasis of the cardiovascular system and in the development of cardiovascular diseases. An abnormal expression or over activation of the local RAS in the heart and vasculature system is one of the most common mechanisms in pathophysiological processes in cardiovascular diseases. This also provides a basis for medical prevention and treatments using chemical approaches. Losartan is a selective nonpeptite antagonist against type 1 angiotensin II receptors (AT1R), and has been applied in medical treatments of a variety of cardiovascular diseases, including essential hypertension. This article reviews direct and indirect cardiovascular effects of losartan on the heart and blood vessels. It summarizes the chemical basis of AT1R for the action site of losartan, focuses on the mechanisms underlying the action of losartan involved in both the heart and vasculature, and reviews the information that may be helpful in the development of new chemical candidates or approaches in the war against cardiovascular diseases.",,"['Xu, Feichao', 'Mao, Caiping', 'Hu, Yali', 'Rui, Can', 'Xu, Zhice', 'Zhang, Lubo']",,,,
,PMC,Docking screens: right for the right reasons?,,PMC3383315,,,"Whereas docking screens have emerged as the most practical way to use protein structure for ligand discovery, an inconsistent track record raises questions about how well docking actually works. In its favor, a growing number of publications report the successful discovery of new ligands, often supported by experimental affinity data and controls for artifacts. Few reports, however, actually test the underlying structural hypotheses that docking makes. To be successful and not just lucky, prospective docking must not only rank a true ligand among the top scoring compounds, it must also correctly orient the ligand so the score it receives is biophysically sound. If the correct binding pose is not predicted, a skeptic might well infer that the discovery was serendipitous. Surveying over 15 years of the docking literature, we were surprised to discover how rarely sufficient evidence is presented to establish whether docking actually worked for the right reasons. The paucity of experimental tests of theoretically predicted poses undermines confidence in a technique that has otherwise become widely accepted. Of course, solving a crystal structure is not always possible, and even when it is, it can be a lot of work, and is not readily accessible to all groups. Even when a structure can be determined, investigators may prefer to gloss over an erroneous structural prediction to better focus on their discovery. Still, the absence of a direct test of theory by experiment is a loss for method developers seeking to understand and improve docking methods. We hope this review will motivate investigators to solve structures and compare them with their predictions whenever possible, to advance the field.",,"['Kolb, Peter', 'Irwin, John J.']",,,,
,PMC,"The Identification, Characterization and Optimization of Small Molecule Probes of Cysteine Proteases: Experiences of the Penn Center for Molecular Discovery with Cathepsin B and Cathepsin L",,PMC2909000,,,"During the pilot phase of the NIH Molecular Library Screening Network, the Penn Center for Molecular Discovery focused on a series of projects aimed at high throughput screening and the development of probes of a variety of protease targets. This review provides our medicinal chemistry experience with two such targets – cathepsin B and cathepsin L. We describe our approach for hit validation, characterization and triage that led to a critical understanding of the nature of hits from the cathepsin B project. In addition, we detail our experience at hit identification and optimization that led to the development of a novel thiocarbazate probe of cathepsin L.",,"['Huryn, Donna M.', 'Smith, Amos B.']",,,,
,PMC,Inflammation on the Mind: Visualizing Immunity in the Central Nervous System,http://dx.doi.org/10.1007/978-3-540-93864-4_10,PMC4988846,,,"The central nervous system (CNS) is a remarkably complex structure that utilizes electrochemical signaling to coordinate activities throughout the entire body. Because the nervous system contains nonreplicative cells, it is postulated that, through evolutionary pressures, this compartment has acquired specialized mechanisms to limit damage. One potential source of damage comes from our immune system, which has the capacity to survey the CNS and periphery for the presence of foreign material. The immune system is equipped with numerous effector mechanisms and can greatly alter the homeostasis and function of the CNS. Degeneration, autoimmunity, and pathogen infection can all result in acute, and sometimes chronic, inflammation within the CNS. Understanding the specialized functionality of innate and adaptive immune cells within the CNS is critical to the design of more efficacious treatments to mitigate CNS inflammatory conditions. Much of our knowledge of CNS-immune interactions stems from seminal studies that have used static and dynamic imaging approaches to visualize inflammatory cells responding to different CNS conditions. This review will focus on how imaging techniques have elevated our understanding of CNS inflammation as well as the exciting prospects that lie ahead as we begin to pursue investigation of the inflamed CNS in real time.",,"['Kang, Silvia S.', 'McGavern, Dorian B.']",,,,
,PMC,"Chloroplast-Derived Vaccine Antigens and Biopharmaceuticals: Expression, Folding, Assembly and Functionality",http://dx.doi.org/10.1007/978-3-540-70868-1_3,PMC2764311,,,"Chloroplast genetic engineering offers several advantages, including high levels of transgene expression, transgene containment via maternal inheritance, and multi-gene expression in a single transformation event. Oral delivery is facilitated by hyperexpression of vaccine antigens against cholera, tetanus, anthrax, plague, or canine parvovirus (4%–31% of total soluble protein, TSP) in transgenic chloroplasts (leaves) or non-green plastids (carrots, tomato) as well as the availability of antibiotic free selectable markers or the ability to excise selectable marker genes. Hyperexpression of several therapeutic proteins, including human serum albumin (11.1% TSP), somatotropin (7% TSP), interferon-alpha (19% TSP), interferon-gamma (6% TSP), and antimicrobial peptide (21.5% TSP), facilitates efficient and economic purification. Also, the presence of chaperones and enzymes in chloroplasts facilitates assembly of complex multisubunit proteins and correct folding of human blood proteins with proper disulfide bonds. Functionality of chloroplast-derived vaccine antigens and therapeutic proteins has been demonstrated by several assays, including the macrophage lysis assay, GM1-ganglioside binding assay, protection of HeLA cells or human lung carcinoma cells against encephalomyocarditis virus, systemic immune response, protection against pathogen challenge, and growth or inhibition of cell cultures. Purification of human proinsulin has been achieved using novel purification strategies (inverse temperature transition property) that do not require expensive column chromatography techniques. Thus, transgenic chloroplasts are ideal bioreactors for production of functional human and animal therapeutic proteins in an environmentally friendly manner.",,"['Chebolu, S.', 'Daniell, H.']",,,,
,PMC,“Small Stem Cells” in Adult Tissues: Very Small Embryonic-Like Stem Cells (VSELs) Stand Up!,http://dx.doi.org/10.1002/cyto.a.20665,PMC2647802,,,"This review summarizes information regarding the rare population of very small embryonic-like stem cells (VSELs) that has been identified in adult tissues, emphasizing both their unique morphological features and potential biological significance. We focus on their pluripotent nature and expression of markers characteristic for embryonic stem cells (ESCs), epiblast (EP)SCs, and primordial germ cells (PGCs). Furthermore, we will discuss their rank in the developmental hierarchy of the SC compartment as well as their relationship to other bone marrow-derived, primitive, non-hematopoietic SCs including: i) endothelial progenitor cells (EPCs); ii) mesenchymal (M)SCs; iii) multipotent adult progenitor cells (MAPCs); iv) marrow-isolated adult multilineage inducible (MIAMIs) cells; v) multipotent adult (MA)SCs; and vi) OmniCytes. We will also present different populations of very “small SCs” that have been recently described in the literature (e.g., spore-like cells and Lin(-)/ALDH(high) long-term repopulating hematopoietic SCs).",,"['Zuba-Surma, Ewa K.', 'Kucia, Magdalena', 'Ratajczak, Janina', 'Ratajczak, Mariusz Z.']",,,,
,PMC,Induction of mucosal immunity in the avian Harderian gland with a replication-deficient Ad5 vector expressing avian influenza H5 hemagglutinin,http://dx.doi.org/10.1016/j.dci.2008.07.018,PMC2931278,,,"The chicken Harderian gland (HG) plays an important role in adaptive immune responses upon ocular exposure to avian pathogens such as avian influenza (AI). To determine the role of HGs in generating immunity, chickens were immunized ocularly with an adenovirus (Ad5) vector expressing the AI hemagglutinin H5 gene. The Ad5-H5 vector induced H5 transgene expression and induced H5- and Ad5-specific IgA and IgG spot-forming cells (SFCs) in the HGs. The IgA and IgG SFC peaked on day 9 for Ad5 and day 11 for the H5 protein. In addition, Ad5- and H5-specific antibodies were induced in serum. IgA in chicken tears was predominantly dimeric, while in serum monomeric IgA was most abundant. Analysis of HG mRNA confirmed expression of the polymeric immunoglobulin receptor (pIgR). These data demonstrated the importance of HGs to generate mucosal and systemic immunity to AI following ocular Ad5-H5 administration to chickens.",,"['van Ginkel, Frederik W.', 'Tang, De-chu C.', 'Gulley, Stephen L.', 'Toro, Haroldo']",,,,
,PMC,Use of humanized severe combined immunodeficient mice for human vaccine development,http://dx.doi.org/10.1586/14760584.8.1.113,PMC2677709,,,"The severe combined immunodeficient (SCID) mouse has no adaptive immunity, lacking mature T and B cells in the peripheral blood or the lymphoid organs. It has been used extensively in biomedical research as a valuable translational model for xeno-engraftment of human tissues and cells. This review focuses on the engraftment of human peripheral blood cells and tissues in SCID mice, as well as in the newly established and more permissive SCID mice deficient in the IL-2 receptor γ-chain. Human immune responses could be elicited and assessed in these humanized SCID mice upon vaccination or sensitization with allogeneic tissues. A translational model is proposed to attain preclinical data for testing human vaccines.",,"['Koo, Gloria C', 'Hasan, Aisha', 'O’Reilly, Richard J']",,,,
,PMC,Proteomic analysis reveals Hrs UIM-mediated ubiquitin signaling in multiple cellular processes,http://dx.doi.org/10.1111/j.1742-4658.2008.06760.x,PMC2647816,,,"Despite the critical importance of protein ubiquitination in regulation of diverse cellular processes, the molecular mechanisms by which cells recognize and transmit ubiquitin signals remain poorly understood. The endosomal sorting machinery component hepatocyte growth factor regulated tyrosine kinase substrate (Hrs) contains an ubiquitin-interacting motif (UIM), which is believed to bind ubiquitinated membrane cargo proteins and mediate their sorting to the lysosomal degradation pathway. To gain insight into the role of Hrs UIM-mediated ubiquitin signaling in cells, we performed a proteomic screen for Hrs UIM-interacting ubiquitinated proteins in human brain by using an in vitro expression cloning (IVEC) screening approach. We have identified 48 ubiquitinated proteins that are specifically recognized by the UIM domain of Hrs. Among them, 12 are membrane proteins which are likely to be Hrs cargo proteins, and 4 are membrane protein-associated adaptor proteins whose ubiquitination may act as a signal to target their associated membrane cargo for Hrs-mediated endosomal sorting. Other classes of the identified proteins include components of the vesicular trafficking machinery, cell signaling molecules, proteins associated with the cytoskeleton and cytoskeleton-dependent transport, and enzymes involved in ubiquitination and metabolism, suggesting the involvement of Hrs UIM-mediated ubiquitin signaling in regulation of multiple cellular processes. We have characterized the ubiquitination of two identified proteins, Munc18-1 and Hsc70, and their interaction with Hrs UIM and provided functional evidence supporting a role for Hsc70 in regulation of Hrs-mediated endosome-to-lysosome trafficking.",,"['Pridgeon, Julia W.', 'Webber, Elizabeth A.', 'Sha, Di', 'Li, Lian', 'Chin, Lih-Shen']",,,,
,PMC,Ebolavirus glycoprotein structure and mechanism of entry,http://dx.doi.org/10.2217/fvl.09.56,PMC2829775,,,"Ebolavirus (EBOV) is a highly virulent pathogen capable of causing a severe hemorrhagic fever with 50–90% lethality. The EBOV glycoprotein (GP) is the only virally expressed protein on the virion surface and is critical for attachment to host cells and catalysis of membrane fusion. Hence, the EBOV GP is a critical component of vaccines as well as a target of neutralizing antibodies and inhibitors of attachment and fusion. The crystal structure of the Zaire ebolavirus GP in its trimeric, prefusion conformation (3 GP(1) plus 3 GP(2)) in complex with a neutralizing antibody fragment, derived from a human survivor of the 1995 Kikwit outbreak, was recently determined. This is the first near-complete structure of any filovirus glycoprotein. The overall molecular architecture of the Zaire ebolavirus GP and its role in viral entry and membrane fusion are discussed in this article.",,"['Lee, Jeffrey E', 'Saphire, Erica Ollmann']",,,,
,PMC,Unraveling the complexities of the interferon response during SARS-CoV infection,http://dx.doi.org/10.2217/17460794.4.1.71,PMC2680287,,,"Viruses employ different strategies to circumvent the antiviral actions of the innate immune response. SARS coronavirus (SARS-CoV), a virus that causes severe lung damage, encodes an array of proteins able to inhibit induction and signaling of type-I interferons. However, recent studies have demonstrated that interferons are produced during SARS-CoV infection in humans and macaques. Furthermore, nuclear translocation of activated STAT1 and a range of interferon-stimulated genes could be demonstrated in the lungs of SARS-CoV-infected macaques. In line with these observations, plasmacytoid dendritic cells have been shown to produce interferons upon SARS-CoV infection in vitro. Given the pivotal role of interferons during viral infections, (differential) induction of interferons may affect the outcome of the infection. Therefore, the functional implication of interferon production during SARS-CoV infection remains to be re-investigated.",,"['de Lang, Anna', 'Baas, Tracey', 'Smits, Saskia L', 'Katze, Michael G', 'Osterhaus, Albert DME', 'Haagmans, Bart L']",,,,
,PMC,Advancing full length genome sequencing for human RNA viral pathogens,http://dx.doi.org/10.2217/17460794.4.1.47,PMC2638583,,,"In the face of numerous emerging and re-emerging viral threats, large-scale genome sequencing efforts are underway to monitor viral evolution in real-time. To fully appreciate the mechanisms of viral adaptation and evolution, and to also develop reagents and resources for a better molecular diagnosis of emerging and re-emerging viral infections, there has been an increasing effort toward producing full length viral genome sequences. To date, high-throughput platforms have been developed using traditional Sanger-based sequencing and there are currently prospects to apply next generation sequencing methods to develop an ultra high-throughput strategy for viral genome sequencing and analysis.",,"['Djikeng, Appolinaire', 'Spiro, David']",,,,
,PMC,Human genetic approaches to diseases of lymphocyte activation,http://dx.doi.org/10.1007/s12026-008-8045-x,PMC3415228,,,"Our laboratory focuses on the study of the molecular regulation of T lymphocyte homeostasis, particularly as it relates to immunological tolerance, apoptosis, and autoimmune diseases. Through intense molecular research on the regulation of lymphocyte fate, the Fas receptor and other tumor necrosis factor receptors as well as their ligands have emerged as key regulators of T lymphocyte apoptosis. We are studying genetic abnormalities of this death pathway, particularly in the context of autoimmune lymphoproliferative syndrome (ALPS) and other non-ALPS conditions affecting lymphocyte homeostasis. These studies have led to further investigations of the regulation of the NF-κB signaling pathway, the molecular basis for programmed cell death and viral cytopathicity, mechanisms of autoimmunity, and regulation of mature T-cell tolerance. Our investigations promise to provide insight into the molecular mechanisms behind the regulation of immune response and contribute to the development of novel diagnostic and treatment methods for autoimmune diseases.",,"['Prabhakar, Madhavi', 'Lenardo, Michael J.']",,,,
,PMC,Learning from molecular sleuths,http://dx.doi.org/10.1016/j.jaci.2008.11.029,PMC4418539,,,,,"['Gern, James E.', 'Busse, William W.']",,,,
,PMC,A Comparative Docking Study of Anibamine as the First Natural Product CCR5 Antagonist in CCR5 Homology Models,http://dx.doi.org/10.1021/ci800356a,PMC2656111,,,"Anibamine, a novel pyridine quaternary alkaloid recently isolated from Aniba sp., has been found to effectively bind to the chemokine receptor CCR5 with an IC(50) at 1 μM in competition with (125)I-gp120, an HIV viral envelope protein binding to CCR5 with high affinity. Since CCR5, a G-protein-coupled receptor, is an essential co-receptor for the human immunodeficiency virus type I (HIV-1) entry to host cells, a CCR5 antagonist that inhibits the cellular entry of HIV-1 provides a new therapy choice for the treatment of HIV. Anibamine provides a novel structural skeleton that is remarkably different from all lead compounds previously identified as CCR5 antagonists. Here, we report comparative docking studies of anibamine with several other known CCR5 antagonists in two CCR5 homology models built based on the crystal structures of bovine rhodopsin and human β(2)-adrenergic receptor. The binding pocket of anibamine has some common features shared with other high affinity CCR5 antagonists, suggesting that they may bind in similar binding sites and/or modes. At the same time, several unique binding features of anibamine were identified and it will likely prove beneficial in future molecular design of novel CCR5 antagonists based on the anibamine scaffold.",,"['Li, Guo', 'Haney, Kendra M.', 'Kellogg, Glen E.', 'Zhang, Yan']",,,,
,PMC,Detection of Disease Outbreaks by the Use of Oral Manifestations,http://dx.doi.org/10.1177/0022034508327546,PMC3144048,,,"Oral manifestations of diseases caused by bioterrorist agents could be a potential data source for biosurveillance. This study had the objectives of determining the oral manifestations of diseases caused by bioterrorist agents, measuring the prevalence of these manifestations in emergency department reports, and constructing and evaluating a detection algorithm based on them. We developed a software application to detect oral manifestations in free text and identified positive reports over three years of data. The normal frequency in reports for oral manifestations related to anthrax (including buc-cal ulcers-sore throat) was 7.46%. The frequency for tularemia was 6.91%. For botulism and smallpox, the frequencies were 0.55% and 0.23%. We simulated outbreaks for these bioterrorism diseases and evaluated the performance of our system. The detection algorithm performed better for smallpox and botulism than for anthrax and tularemia. We found that oral manifestations can be a valuable tool for biosur-veillance.",,"['Torres-Urquidy, M.H.', 'Wallstrom, G.', 'Schleyer, T.K.L.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.02394-08,PMC2612347,,,,,,,,,
,PMC,Democracy and Women's Health,http://dx.doi.org/10.4103/0973-1229.42101,PMC3151452,21836777,CC BY-NC-SA,"New research on broader determinants of health has culminated into the new paradigm of social determinants of health. The fundamental view that underlies this new paradigm is that socioeconomic and political contexts in which people live have significant bearing upon their health and well-being. Unlike a wealth of research on socioeconomic determinants, few studies have focused on the role of political factors. Some of these studies examine the role of political determinants on health through their mediation with the labour environments and systems of welfare state. A few others study the relationship between polity regimes and population health more directly. However, none of them has a focus on women's health. This study explores the interactions, both direct and indirect, between democracy and women's health. In doing so, it identifies some of the main health vulnerabilities for women and explains, through a conceptual model, how democracy and respect for human rights interacts with women's health.",2009 Jan-Dec,"Safaei, Jalil",Mens Sana Monogr,,,
,PMC,Construction of a Large Naïve Human Phage-Displayed Fab Library Through One-Step Cloning,http://dx.doi.org/10.1007/978-1-59745-554-1_6,PMC3423197,,,"Antibody-based therapeutics is attracting more attention in the post-genome era, in contrast to a diminution in the initial high expectation for rapid development of gene-based therapeutic modalities. In support to the antibody-based therapeutics, the advent of recent technologies has made human antibody screening and production progressively more economic. Among those technologies, phage-display antibody library has been successfully applied in the antibody-based drug development both as fully human antibody sources and tools for antibody engineering. Building up a high-quality antibody library with a large library size and high diversity has been crucial for successful isolation of antibodies. Here we describe an efficient strategy for the construction of a large naïve phage-display human Fab library with one-step cloning. Optimization of each key step is extensively discussed and simplified protocols for library panning and Fab production are also described.",,"['Zhu, Zhongyu', 'Dimitrov, Dimiter S.']",,,,
,PMC,Therapeutic Antibodies: Current State and Future Trends – Is a Paradigm Change Coming Soon?,http://dx.doi.org/10.1007/978-1-59745-554-1_1,PMC3402212,,,"Antibody-based therapeutics currently enjoy unprecedented success, growth in research and revenues, and recognition of their potential. It appears that the promise of the “magic bullet” has largely been realized. There are currently 22 monoclonal antibodies (mAbs) approved by the United States Food and Drug Administration (FDA) for clinical use and hundreds are in clinical trials for treatment of various diseases including cancers, immune disorders, and infections. The revenues from the top five therapeutic antibodies (Rituxan, Remicade, Herceptin, Humira, and Avastin) nearly doubled from $6.4 billion in 2004 to $11.7 billion in 2006. During the last several years major pharmaceutical companies raced to acquire antibody companies, with a recent example of MedImmune being purchased for $15.6 billion by AstraZeneca. These therapeutic and business successes reflect the major advances in antibody engineering which have resulted in the generation of safe, specific, high-affinity, and non-immunogenic antibodies during the last three decades. Currently, second and third generations of antibodies are under development, mostly to improve already existing antibody specificities. However, although the refinement of already known methodologies is certainly of great importance for potential clinical use, there are no conceptually new developments in the last decade comparable, for example, to the development of antibody libraries, phage display, domain antibodies (dAbs), and antibody humanization to name a few. A fundamental question is then whether there will be another change in the paradigm of research as happened 1–2 decades ago or the current trend of gradual improvement of already developed methodologies and therapeutic antibodies will continue. Although any prediction could prove incorrect, it appears that conceptually new methodologies are needed to overcome the fundamental problems of drug (antibody) resistance due to genetic or/and epigenetic alterations in cancer and chronic infections, as well as problems related to access to targets and complexity of biological systems. If new methodologies are not developed, it is likely that gradual saturation will occur in the pipeline of conceptually new antibody therapeutics. In this scenario we will witness an increase in combination of targets and antibodies, and further attempts to personalize targeted treatments by using appropriate biomarkers as well as to develop novel scaffolds with properties that are superior to those of the antibodies now in clinical use.",,"['Dimitrov, Dimiter S.', 'Marks, James D.']",,,,
,PMC,Preparation of Recombinant Viral Glycoproteins for Novel and Therapeutic Antibody Discovery,http://dx.doi.org/10.1007/978-1-59745-554-1_2,PMC3277858,,,"Neutralizing antibodies are a critical component in the protection or recovery from viral infections. In the absence of available vaccines or antiviral drugs for many important human viral pathogens, the identification and characterization of new human monoclonal antibodies (hmAbs) able to neutralize viruses offers the possibility for effective pre- and/or post-exposure therapeutic modalities. Such hmAbs may also help in our understanding of the virus entry process, the mechanisms of virus neutralization and in the eventual development of specific entry inhibitors, vaccines and research tools. The majority of the more recently developed antiviral hmAbs have come from the use of antibody phage-display technologies using both naïve and immune libraries. Many of these agents are also enveloped viruses possessing important neutralizing determinants within their membrane-anchored envelope glycoproteins and the use of recombinant, soluble versions of these viral glycoproteins is often critical in the isolation and development of antiviral hmAbs. This chapter will detail several methods that have been successfully employed to produce, purify and characterize soluble and secreted versions of several viral envelope glycoproteins which have been successfully used as antigens to capture and isolate human phage-displayed monoclonal antibodies.",,"['Chan, Yee-Peng', 'Yan, Lianying', 'Feng, Yan-Ru', 'Broder, Christopher C.']",,,,
,PMC,Polypyrrole-peptide microarray for biomolecular interaction analysis by SPR imaging,http://dx.doi.org/10.1007/978-1-60327-394-7_17,PMC2929587,,,"Nowadays, high-throughput analysis of biological events is a great challenge which could take benefit of the recent development of microarray devices. The great potential of such technology is related to the availability of a chip bearing a large set of probes, stable and easy to obtain, and suitable for ligand binding detection. Here, we described a new method based on polypyrrole chemistry and allowing the covalent immobilization of peptides in a microarray format and on a gold surface compatible with the use of Surface Plasmon Resonance. This technique is then illustrated by the detection and characterization of antibodies induced by hepatitis C virus and present in patients’serums.",,"['Villiers, Marie-Bernadette', 'Cortès, Sandra', 'Brakha, Carine', 'Marche, Patrice', 'Roget, André', 'Livache, Thierry']",,,,
,PMC,Antibody Fragment Expression and Purification,http://dx.doi.org/10.1007/978-1-59745-554-1_25,PMC2858623,,,"Interest in the potential of monoclonal antibodies (mAbs) to serve as therapeutic agents has surged in the past decade with a major emphasis on human viral diseases. There has been much attention in this area directed towards the human immunodeficiency virus type-1 (HIV-1) and promising research developments have emerged on the inhibition of HIV-1 infection by mAbs and the identification of several highly conserved neutralizing epitopes. More recently, potent fully-human neutralizing mAbs have been developed against a variety of important human viral disease agents including the paramyxoviruses Hendra virus and Nipah virus, and human or humanized mAbs have been developed against severe acute respiratory syndrome coronavirus (SARS CoV), and West Nile virus, among others. Most of these more recently developed antiviral mAbs have come from the use of antibody phage-display technologies and the implementation of simplified, inexpensive yet efficient methods, for expressing and purifying the initially selected fragment antibodies is of prime importance in further facilitating this area of research.",,"['Dimitrova, Dimana', 'Choudhry, Vidita', 'Broder, Christopher C.']",,,,
,PMC,A Versatile Bifunctional Dendritic Cell Targeting Vaccine Vector,http://dx.doi.org/10.1021/mp800111a,PMC2678937,,,"We have developed an efficient versatile in vivo dendritic cell (DC) targeting vector for delivering different classes of antigens such as proteins, peptide, glycolipids and naked DNA for vaccine applications. A single chain antibody (scFv) that recognizes DEC-205 receptor of DC was fused with a core-streptavidin domain and expressed in Escherichia coli using the T7 expression system. The bifunctional fusion protein (bfFp) was expressed as a periplasmic soluble protein and affinity-purified in its monomeric form. The bifunctional activity against DEC-205 and biotin was characterized by ELISA and Western blot. In vivo DC targeting of a diverse group of biotinylated antigens such as viral and bacterial proteins, a cancer peptide, gangliosides and DNA of certain infectious diseases was conducted in mice. Results show that in the presence of bfFp and costimulatory anti-CD40 mAb, both humoral and cell-mediated responses were augmented in either the single antigen or multiple antigen targeting strategy. Lastly, bfFp based DC targeting of antigens in low doses may be a useful strategy for the design of monovalent or polyvalent vaccines for the masses.",,"['Wang, Welson W.', 'Das, Dipankar', 'Suresh, Mavanur R.']",,,,
,PMC,Rhinoviruses are a major cause of wheezing and hospitalization in children less than 2 years of age,http://dx.doi.org/10.1097/INF.0b013e3181861da0,PMC4639321,,,"BACKGROUND: Human rhinoviruses (HRV) are now considered major respiratory pathogens. We sought to determine whether HRV are a cause of wheezing and/or hospitalization in children < 2 years old. METHODS: A PCR assay was used to screen for HRV infection in 4 categories of children < 2 years old: 1) with symptoms of respiratory tract disease without wheezing; 2) with wheezing with or without other symptoms; 3) who were asymptomatic and; 4) who had a respiratory specimen submitted to a diagnostic laboratory. All specimens were collected between January and December, 2004. Phylogenetic analyses were performed on most HRV isolates. RESULTS: Twenty-eight (17%) of 165 children with symptoms of respiratory infection without wheezing; 21 (26.3%) of 80 children with wheezing; 3 (3%) of 93 asymptomatic children and 47 (23.3%) of 202 children with specimens submitted to the diagnostic laboratory tested positive for HRV. The difference between the rates of infection in the asymptomatic group and in each of the three other categories was statistically significant (p≤0.01). Among HRV-positive children with samples submitted to the diagnostic laboratory, 55% were hospitalized which was similar to that observed for respiratory syncytial virus (52.7%) among children of a similar age group and time period (P=0.85). Diverse groups of HRV were circulating during the one-year study period. CONCLUSIONS: HRV are important pathogens among children < 2 years old and are responsible for a significant proportion of wheezing this age group. The hospitalization rates of HRV-positive children appear to be similar to that of RSV.",,"['Piotrowska, Zofia', 'Vazquez, Marietta', 'Shapiro, Eugene D.', 'Weibel, Carla', 'Ferguson, David', 'Landry, Marie L.', 'Kahn, Jeffrey S.']",,,,
,PMC,Investigation of antimicrobial and protease-inhibitory activity from cultured cyanobacteria,http://dx.doi.org/10.1080/13880200802415483,PMC3061310,,,"A culture collection of cyanobacteria has been established at the University of Illinois at Chicago. This collection includes marine, terrestrial, and freshwater strains and contains representatives of the five orders of cyanobacteria: Chroococcales, Pleurocapsales, Oscillatoriales, Nostocales, and Stigonematales. In this study, extracts from a subset of 61 strains, 16 marine and 45 freshwater/terrestrial, were evaluated against three current protease targets, i.e. 20S proteasome and two SARS viral proteases, two important bacterial targets, i.e. Mycobacterium tuberculosis and Bacillus anthracis, and in the Artemia salina toxicity assay. In total, extracts of 12 strains possessed significant levels of activity in one or more targets. The overwhelming majority of active extracts (11 of 12) were from either freshwater or terrestrial forms of cyanobacteria, with the greater part of these (9 of 12) being heterocyst-forming strains. These results further support the use of cultured cyanobacteria as a source of biologically active natural products.",,"['Chlipala, George', 'Mo, Shunyan', 'Carcache de Blanco, Esperanza J.', 'Ito, Aiko', 'Bazarek, Stanley', 'Orjala, Jimmy']",,,,
,PMC,Integrating Occupational Health with Mainstream Public Health in Massachusetts: An Approach to Intervention,,PMC2707268,,,"In the late 19th century, workers' health was among the central concerns of the social reform movement to improve public health. Today, few state health agencies have comprehensive occupational health programs. Yet, state public health agencies have critical roles to play in occupational health and may be particularly instrumental in addressing the occupational health needs of underserved worker populations. Since the mid-1980s, with support from the National Institute for Occupational Safety and Health, the Massachusetts Department of Public Health has been working to build an occupational health program and promote the integration of occupational health concerns with ongoing public health activities in the state. This article provides a framework for considering the range of integration activities and presents examples of successful occupational health integration efforts in Massachusetts.",,"['Davis, Letitia', 'Souza, Kerry']",,,,
,PMC,Assessing Public Health Capabilities During Emergency Preparedness Tabletop Exercises: Reliability and Validity of a Measurement Tool,,PMC2602939,,,"OBJECTIVES: Improving the ability of local public health agencies to respond to large-scale emergencies is an ongoing challenge. Tabletop exercises can provide an opportunity for individuals and groups to practice coordination of emergency response and evaluate performance. The purpose of this study was to develop a valid and reliable self-assessment performance measurement tool for tabletop exercise participants. METHODS: The study population comprised 179 public officials who attended three tabletop exercises in Massachusetts and Maine between September 2005 and November 2006. A 42-item questionnaire was developed to assess five public health functional capabilities: (1) leadership and management, (2) mass casualty care, (3) communication, (4) disease control and prevention, and (5) surveillance and epidemiology. Analyses were undertaken to examine internal consistency, associations among scales, the empirical structure of the items, and inter-rater agreement. RESULTS: Thirty-seven questions were retained in the final questionnaire and grouped according to the original five domains. Alpha coefficients were 0.81 or higher for all scales. The five-factor solution from the principal components analysis accounted for 60% of the total variance, and the factor structure was consistent with the five domains of the original conceptual model. Inter-rater agreement ranged from good to excellent. CONCLUSIONS: The resulting 37-item performance measurement tool was found to reliably measure public health functional capabilities in a tabletop exercise setting, with preliminary evidence of a factor structure consistent with the original conceptualization and of criterion-related validity.",,"['Savoia, Elena', 'Testa, Marcia A.', 'Biddinger, Paul D.', 'Cadigan, Rebecca O.', 'Koh, Howard', 'Campbell, Paul', 'Stoto, Michael A.']",,,,
,PMC,Progress towards recombinant anti-infective antibodies,,PMC2800955,,,"The global market for monoclonal antibody therapeutics reached a total of $11.2 billion in 2004, with an impressive 42% growth rate over the previous five years and is expected to reach ~$34 billion by 2010. Coupled with this growth are stream-lined product development, production scale-up and regulatory approval processes for the highly conserved antibody structure. While only one of the 21 current FDA-approved antibodies, and one of the 38 products in advanced clinical trials target infectious diseases, there is increasing academic, government and commercial interest in this area. Synagis, an antibody neutralizing respiratory syncitial virus (RSV), garnered impressive sales of $1.1 billion in 2006 in spite of its high cost and undocumented effects on viral titres in human patients. The success of anti-RSV passive immunization has motivated the continued development of anti-infectives to treat a number of other infectious diseases, including those mediated by viruses, toxins and bacterial/fungal cells. Concurrently, advances in antibody technology suggest that cocktails of several monoclonal antibodies with unique epitope specificity or single monoclonal antibodies with broad serotype specificity may be the most successful format. Recent patents and patent applications in these areas will be discussed as predictors of future anti-infective therapeutics.",,"['Pai, Jennifer C.', 'Sutherland, Jamie N.', 'Maynard, Jennifer A.']",,,,
,PMC,Pathobiology of secondary immune thrombocytopenia,http://dx.doi.org/10.1053/j.seminhematol.2008.12.005,PMC2682438,,,"Primary immune thrombocytopenic purpura (ITP) remains a diagnosis of exclusion both from nonimmune causes of thrombocytopenia and immune thrombocytopenia that develops in the context of other disorders (secondary immune thrombocytopenia). The pathobiology, natural history, and response to therapy of the diverse causes of secondary ITP differ from each other and from primary ITP, so accurate diagnosis is essential. Immune thrombocytopenia can be secondary to medications or to a concurrent disease, such as an autoimmune condition (eg, systemic lupus erythematosus [SLE], antiphospholipid antibody syndrome [APS], immune thyroid disease, or Evans syndrome), a lymphoproliferative disease (eg, chronic lymphocytic leukemia or large granular T-lymphocyte lymphocytic leukemia), or chronic infection, eg, with Helicobacter pylori, human immunodeficiency virus (HIV), or hepatitis C virus (HCV). Response to infection may generate antibodies that cross-react with platelet antigens (HIV, H pylori) or immune complexes that bind to platelet Fcγ receptors (HCV) and platelet production may be impaired by infection of megakaryocyte bone marrow-dependent progenitor cells (HCV and HIV), decreased production of thrombopoietin (TPO), and splenic sequestration of platelets secondary to portal hypertension (HCV). Sudden and severe onset of thrombocytopenia has been observed in children after vaccination for measles, mumps, and rubella or natural viral infections, including Epstein-Barr virus, cytomegalovirus, and varicella zoster virus. This thrombocytopenia may be caused by cross-reacting antibodies and closely mimics acute ITP of childhood. Proper diagnosis and treatment of the underlying disorder, where necessary, play an important role in patient management.",,"['Cines, Douglas B.', 'Liebman, Howard', 'Stasi, Roberto']",,,,
,PMC,Changes in H5N1 influenza virus hemagglutinin receptor binding domain affect systemic spread,http://dx.doi.org/10.1073/pnas.0811052106,PMC2629220,,,"The HA of influenza virus is a receptor-binding and fusion protein that is required to initiate infection. The HA receptor-binding domain determines the species of sialyl receptors recognized by influenza viruses. Here, we demonstrate that changes in the HA receptor-binding domain alter the ability of the H5N1 virus to spread systemically in mice. The A/Vietnam/1203/04 (VN1203) and A/Hong Kong/213/03 (HK213) viruses are consistently lethal to domestic chickens but differ in their pathogenicity to mammals. Insertion of the VN1203 HA and neuraminidase (NA) genes into recombinant HK213 virus expanded its tissue tropism and increased its lethality in mice; conversely, insertion of HK213 HA and NA genes into recombinant VN1203 virus decreased its systemic spread and lethality. The VN1203 and HK213 HAs differ by 10 aa, and HK213 HA has shown greater binding affinity for synthetic α2,6-linked sialyl receptor. Introduction of an S227N change and removal of N-linked glycosylation at residue 158 increased the α2,6-binding affinity of VN1203 HA. Recombinant VN1203 virus carrying the S227N change alone or with the residue-158 glycosylation site removed showed reduced lethality and systemic spread in mice but not in domestic chickens. Wild-type VN1203 virus exhibited the greatest efficiency in systemic spread after intramuscular inoculation and in infection of mouse bone marrow-derived dendritic cells and conventional pulmonary dendritic cells. These results show that VN1203 HA glycoprotein confers pathogenicity by facilitating systemic spread in mice; they also suggest that a minor change in receptor binding domain may modulate the virulence of H5N1 viruses.",,"['Yen, Hui-Ling', 'Aldridge, Jerry R.', 'Boon, Adrianus C. M.', 'Ilyushina, Natalia A.', 'Salomon, Rachelle', 'Hulse-Post, Diane J.', 'Marjuki, Henju', 'Franks, John', 'Boltz, David A.', 'Bush, Dorothy', 'Lipatov, Aleksandr S.', 'Webby, Richard J.', 'Rehg, Jerold E.', 'Webster, Robert G.']",,,,
,PMC,Random dissection to select for protein split sites and its application in protein fragment complementation,http://dx.doi.org/10.1002/pro.42,PMC2708047,,,"To identify protein split sites quickly, a selection procedure by using chloramphenicol acetyl transferase (CAT) as reporter was introduced to search for folded protein fragments from libraries generated by random digestion and reassembly of the target gene, which yielded an abundant amount of DNA fragments with controllable lengths. Experimental results of tryptophan synthase alpha subunit (TSα) and TEM-1 β-lactamase agreed well with what the literature has reported. The solubility of these fragments correlated roughly with the minimum inhibitory concentrations of the CAT fusions. The application of this dissection protocol to protein fragment complementation assay (PCA) was evaluated using aminoglycoside-3′-phosphotransferase I (APH(3′)-I) as a model protein. Three nearly bisectional sites and a number of possible split points were identified, and guided by this result, four novel pairs of fragments were tested for complementation. Three out of four pairs partially restored the APH activity with the help of leucine zippers, and a truncated but active APH(3′)-I (Δ1–25) was also found. Finally, the weakly active APH(3′)-I-(1–253)NZ/CZ (254–271) containing a short 18 residue tag was further improved by error-prone PCR, and a best mutant was obtained showing a fourfold improvement after just one round of evolution. These results demonstrate that protein random dissection based on the CAT selection can provide an efficient search for protein breakage points and guide the design of fragments for protein complementation assay. Furthermore, more active fragment pairs can be achieved with the classical directed evolution approach.",,"['Chen, Yong', 'Li, Shuang', 'Chen, Tingjian', 'Hua, Hui', 'Lin, Zhanglin']",,,,
,PMC,Efficacy of ribavirin in a case of long lasting and disabling Gianotti-Crosti syndrome,http://dx.doi.org/10.3315/jdcr.2008.1022,PMC3157781,,,"BACKGROUND: Gianotti-Crosti syndrome, also known as papular acrodermatitis of childhood, is an acrally distributed papular eruption occurring mostly in infants and young children. MAIN OBSERVATIONS: A six-year-old girl presented to us with four-month history of a generalized intensely pruritic rash, clinically consistent with Gianotti-Crosti syndrome, following a febrile illness with common cold symptoms. Clinical remission was not achieved despite of several medications. With reluctance and parent's informed consent, we commenced a course of oral ribavirin syrup at a dose of 300mg daily for five days. Dramatic symptomatic remission was noted five days later. CONCLUSION: Further studies are needed to confirm the efficacy of ribavirin in Gianotti-Crosti syndrome.",,"['Zawar, Vijay', 'Chuh, Antonio']",,,,
,PMC,SARS-CoV proteins decrease levels and activity of human ENaC via activation of distinct PKC isoforms,http://dx.doi.org/10.1152/ajplung.90437.2008,PMC2660211,,,"Among the multiple organ disorders caused by the severe acute respiratory syndrome coronavirus (SARS-CoV), acute lung failure following atypical pneumonia is the most serious and often fatal event. We hypothesized that two of the hydrophilic structural coronoviral proteins (S and E) would regulate alveolar fluid clearance by decreasing the cell surface expression and activity of amiloride-sensitive epithelial sodium (Na(+)) channels (ENaC), the rate-limiting protein in transepithelial Na(+) vectorial transport across distal lung epithelial cells. Coexpression of either S or E protein with human α-, β-, and γ-ENaC in Xenopus oocytes led to significant decreases of both amiloride-sensitive Na(+) currents and γ-ENaC protein levels at their plasma membranes. S and E proteins decreased the rate of ENaC exocytosis and either had no effect (S) or decreased (E) rates of endocytosis. No direct interactions among SARS-CoV E protein with either α- or γ-ENaC were indentified. Instead, the downregulation of ENaC activity by SARS proteins was partially or completely restored by administration of inhibitors of PKCα/β1 and PKCζ. Consistent with the whole cell data, expression of S and E proteins decreased ENaC single-channel activity in oocytes, and these effects were partially abrogated by PKCα/β1 inhibitors. Finally, transfection of human airway epithelial (H441) cells with SARS E protein decreased whole cell amiloride-sensitive currents. These findings indicate that lung edema in SARS infection may be due at least in part to activation of PKC by SARS proteins, leading to decreasing levels and activity of ENaC at the apical surfaces of lung epithelial cells.",,"['Ji, Hong-Long', 'Song, Weifeng', 'Gao, Zhiqian', 'Su, Xue-Feng', 'Nie, Hong-Guang', 'Jiang, Yi', 'Peng, Ji-Bin', 'He, Yu-Xian', 'Liao, Ying', 'Zhou, Yong-Jian', 'Tousson, Albert', 'Matalon, Sadis']",,,,
,PMC,Theiler's murine encephalomyelitis virus attachment to the gastrointestinal tract is associated with sialic acid binding,http://dx.doi.org/10.1080/13550280802380563,PMC2882804,,,"DA and GDVII are strains of Theiler's murine encephalomyelitis virus (TMEV). DA virus mutant DApB encodes VP2 puff B of GDVII, whereas DApBL2M contains VP1 loop II of GDVII with a point mutation in VP2 puff B. Neuraminidase treatment of cells inhibited infection by DA and DApB, but not GDVII or DApBL2M viruses; sialic acid (SA) binding correlated with virus persistence. In virus binding assays to intestine sections, all four TMEVs bound goblet cells and the mucus of the epithelium that was SA dependent. Therefore, differences in SA composition on different cell types can affect tropism and infection.",,"['Tsunoda, Ikuo', 'Libbey, Jane E', 'Fujinami, Robert S']",,,,
,PMC,Epidemiology of Necrotizing Enterocolitis Temporal Clustering in Two Neonatology Practices,http://dx.doi.org/10.1016/j.jpeds.2008.11.002,PMC2700364,,,"OBJECTIVE: To develop a statistical method for defining clusters of necrotizing enterocolitis (NEC) cases in the neonatal intensive care unit (NICU). STUDY DESIGN: 2782 infants, between 1996–2004, weighing 401–1500 grams at birth were included. NEC was defined as Bell stage II or III. Two statistical methods used to define “disease clusters” were: (1) modified scan test; (2) comparison of observed and expected incidence density rates (IDR) of NEC at each NICU. RESULTS: The proportion of infants with NEC was similar between NICUs (7.1% vs. 7.7%; p=0.6) as was the expected IDR of NEC (1.39/1000 patient-days vs. 1.32/1000 patient-days, p=0.72). Twelve temporal clusters of NEC were identified in the NICUs combined, comprising 18% of 203 total NEC cases during the study period. No seasonal/secular trends were noted for NEC rates or identified clusters. Potential NEC clusters of ≥3 cases at either NICU had >75% chance of being a true NEC cluster. CONCLUSIONS: No operational definition of NEC cluster exists. This study introduced methods to be employed for prospective surveillance and guide studies to investigate etiologic relevance. Utilizing the proposed methods, statistically significant clusters (potential outbreaks) of NEC within NICUs can be identified early, providing early opportunity to implement cluster investigation protocols.",,"['Meinzen-Derr, Jareen', 'Morrow, Ardythe L.', 'Hornung, Richard W.', 'Donovan, Edward F.', 'Dietrich, Kim N.', 'Succop, Paul A.']",,,,
,PMC,Functional analysis of the transmembrane domain in paramyxovirus F protein-mediated membrane fusion,http://dx.doi.org/10.1016/j.jmb.2008.12.029,PMC2750892,,,"To enter cells enveloped viruses use fusion-mediating glycoproteins to facilitate the merger of the viral and host cell membranes. These glycoproteins undergo large-scale irreversible refolding during membrane fusion. The paramyxovirus parainfluenza virus 5 (PIV5) mediates membrane merger through its fusion protein (F). The transmembrane (TM) domains of viral fusion proteins are typically required for fusion. The TM domain of F is particularly interesting in that it is potentially unusually long; multiple calculations suggest a TM helix length between 25 and 48 residues. Oxidative cross-linking of single cysteine substitutions indicates the F TM trimer forms a helical bundle within the membrane. To assess the functional role of the PIV5 F protein TM domain, alanine scanning mutagenesis was performed. Two residues located in the outer leaflet of the bilayer are critical for fusion. Multiple amino acid substitutions at these positions indicate the physical properties of the side chain play a critical role in supporting or blocking fusion. Analysis of intermediate steps in F protein refolding indicated that the mutants were not trapped at the open stalk intermediate or the prehairpin intermediate. Incorporation of a known F protein destabilizing mutation that causes a hyperfusogenic phenotype restored fusion activity to the mutants. Further, altering the curvature of the lipid bilayer by addition of oleic acid promoted fusion of the F protein mutants. In aggregate, these data indicate that the TM domain plays a functional role in fusion beyond merely anchoring the protein in the viral envelope and that it can affect the structures and steady-state concentrations of the various conformational intermediates en route to the final postfusion state. We suggest that the unusual length of this TM helix might allow it to serve as a template for formation of or specifically stabilize the lipid stalk intermediate in fusion.",,"['Bissonnette, Mei Lin Z.', 'Donald, Jason E.', 'DeGrado, William F.', 'Jardetzky, Theodore S.', 'Lamb, Robert A.']",,,,
,PMC,Enhancement of Adeno-Associated Virus Infection by Mobilizing Capsids into and Out of the Nucleolus,http://dx.doi.org/10.1128/JVI.02309-08,PMC2648275,,,"Adeno-associated virus (AAV) serotypes are being tailored for numerous therapeutic applications, but the parameters governing the subcellular fate of even the most highly characterized serotype, AAV2, remain unclear. To understand how cellular conditions control capsid trafficking, we have tracked the subcellular fate of recombinant AAV2 (rAAV2) vectors using confocal immunofluorescence, three-dimensional infection analysis, and subcellular fractionation. Here we report that a population of rAAV2 virions enters the nucleus and accumulates in the nucleolus after infection, whereas empty capsids are excluded from nuclear entry. Remarkably, after subcellular fractionation, virions accumulating in nucleoli were found to retain infectivity in secondary infections. Proteasome inhibitors known to enhance transduction were found to potentiate nucleolar accumulation. In contrast, hydroxyurea, which also increases transduction, mobilized virions into the nucleoplasm, suggesting that two separate pathways influence vector delivery in the nucleus. Using a small interfering RNA (siRNA) approach, we then evaluated whether nucleolar proteins B23/nucleophosmin and nucleolin, previously shown to interact with AAV2 capsids, affect trafficking and transduction efficiency. Similar to effects observed with proteasome inhibition, siRNA-mediated knockdown of nucleophosmin potentiated nucleolar accumulation and increased transduction 5- to 15-fold. Parallel to effects from hydroxyurea, knockdown of nucleolin mobilized capsids to the nucleoplasm and increased transduction 10- to 30-fold. Moreover, affecting both pathways simultaneously using drug and siRNA combinations was synergistic and increased transduction over 50-fold. Taken together, these results support the hypothesis that rAAV2 virions enter the nucleus intact and can be sequestered in the nucleolus in stable form. Mobilization from the nucleolus to nucleoplasmic sites likely permits uncoating and subsequent gene expression or genome degradation. In summary, with these studies we have refined our understanding of AAV2 trafficking dynamics and have identified cellular parameters that mobilize virions in the nucleus and significantly influence AAV infection.",,"['Johnson, Jarrod S.', 'Samulski, R. Jude']",,,,
,PMC,Reovirus μ2 Protein Inhibits Interferon Signaling through a Novel Mechanism Involving Nuclear Accumulation of Interferon Regulatory Factor 9,http://dx.doi.org/10.1128/JVI.01787-08,PMC2643726,,,"The secreted cytokine alpha/beta interferon (IFN-α/β) binds its receptor to activate the Jak-STAT signal transduction pathway, leading to formation of the heterotrimeric IFN-stimulated gene factor 3 (ISGF3) transcription complex for induction of IFN-stimulated genes (ISGs) and establishment of an antiviral state. Many viruses have evolved countermeasures to inhibit the IFN pathway, thereby subverting the innate antiviral response. Here, we demonstrate that the mildly myocarditic reovirus type 1 Lang (T1L), but not the nonmyocarditic reovirus type 3 Dearing, represses IFN induction of a subset of ISGs and that this repressor function segregates with the T1L M1 gene. Concordantly, the T1L M1 gene product, μ2, dramatically inhibits IFN-β-induced reporter gene expression. Surprisingly, T1L infection does not degrade components of the ISGF3 complex or interfere with STAT1 or STAT2 nuclear translocation as has been observed for other viruses. Instead, infection with T1L or reassortant or recombinant viruses containing the T1L M1 gene results in accumulation of interferon regulatory factor 9 (IRF9) in the nucleus. This effect has not been previously described for any virus and suggests that μ2 modulates IRF9 interactions with STATs for both ISGF3 function and nuclear export. The M1 gene is a determinant of virus strain-specific differences in the IFN response, which are linked to virus strain-specific differences in induction of murine myocarditis. We find that virus-induced myocarditis is associated with repression of IFN function, providing new insights into the pathophysiology of this disease. Together, these data provide the first report of an increase in IRF9 nuclear accumulation associated with viral subversion of the IFN response and couple virus strain-specific differences in IFN antagonism to the pathogenesis of viral myocarditis.",,"['Zurney, Jennifer', 'Kobayashi, Takeshi', 'Holm, Geoffrey H.', 'Dermody, Terence S.', 'Sherry, Barbara']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Triggers Apoptosis via Protein Kinase R but Is Resistant to Its Antiviral Activity,http://dx.doi.org/10.1128/JVI.01245-08,PMC2643707,,,"In this study, infection of 293/ACE2 cells with severe acute respiratory syndrome coronavirus (SARS-CoV) activated several apoptosis-associated events, namely, cleavage of caspase-3, caspase-8, and poly(ADP-ribose) polymerase 1 (PARP), and chromatin condensation and the phosphorylation and hence inactivation of the eukaryotic translation initiation factor 2α (eIF2α). In addition, two of the three cellular eIF2α kinases known to be virus induced, protein kinase R (PKR) and PKR-like endoplasmic reticulum kinase (PERK), were activated by SARS-CoV. The third kinase, general control nonderepressible-2 kinase (GCN2), was not activated, but late in infection the level of GCN2 protein was significantly reduced. Reverse transcription-PCR analyses revealed that the reduction of GCN2 protein was not due to decreased transcription or stability of GCN2 mRNA. The specific reduction of PKR protein expression by antisense peptide-conjugated phosphorodiamidate morpholino oligomers strongly reduced cleavage of PARP in infected cells. Surprisingly, the knockdown of PKR neither enhanced SARS-CoV replication nor abrogated SARS-CoV-induced eIF2α phosphorylation. Pretreatment of cells with beta interferon prior to SARS-CoV infection led to a significant decrease in PERK activation, eIF2α phosphorylation, and SARS-CoV replication. The various effects of beta interferon treatment were found to function independently on the expression of PKR. Our results show that SARS-CoV infection activates PKR and PERK, leading to sustained eIF2α phosphorylation. However, virus replication was not impaired by these events, suggesting that SARS-CoV possesses a mechanism to overcome the inhibitory effects of phosphorylated eIF2α on viral mRNA translation. Furthermore, our data suggest that viral activation of PKR can lead to apoptosis via a pathway that is independent of eIF2α phosphorylation.",,"['Krähling, Verena', 'Stein, David A.', 'Spiegel, Martin', 'Weber, Friedemann', 'Mühlberger, Elke']",,,,
,PMC,IL-15 INDEPENDENT MAINTENANCE OF VIRUS-SPECIFIC CD8(+) T CELLS IN THE CNS DURING CHRONIC INFECTION,http://dx.doi.org/10.1016/j.jneuroim.2008.11.005,PMC2679951,,,"The role of IL-15 in T cell survival was examined during chronic CNS coronavirus infection. Similar numbers of virus-specific CD8(+) T cells were retained in the CNS of IL-15(−/−)and wt mice, consistent with loss of IL-2/15 receptor (CD122) expression. IL-15 deficiency also had no affect on IL-7 receptor (CD127) expression, Bcl-2 upregulation, granzyme B expression, or IFN-γ secretion in CNS persisting CD8(+) T cells. Furthermore, CD8(+) T cell division in the CNS was reduced compared to spleen. CD8(+) T cells in the persistently infected CNS are thus characterized by IL-15 independent, low level proliferation and an activated/memory phenotype.",,"['Zuo, Jun', 'Stohlman, Stephen A.', 'Parra, Gabriel I.', 'Bergmann, Cornelia C.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Protein 6 Is Required for Optimal Replication,http://dx.doi.org/10.1128/JVI.02371-08,PMC2643704,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes several accessory proteins of unknown function. One of these proteins, protein 6 (p6), which is encoded by ORF6, enhances virus replication when introduced into a heterologous murine coronavirus (mouse hepatitis virus [MHV]) but is not essential for optimal SARS-CoV replication after infection at a relatively high multiplicity of infection (MOI). Here, we reconcile these apparently conflicting results by showing that p6 enhances SARS-CoV replication to nearly the same extent as when expressed in the context of MHV if cells are infected at a low MOI and accelerates disease in mice transgenic for the human SARS-CoV receptor.",,"['Zhao, Jincun', 'Falcón, Ana', 'Zhou, Haixia', 'Netland, Jason', 'Enjuanes, Luis', 'Pérez Breña, Pilar', 'Perlman, Stanley']",,,,
,PMC,Predicting undetected infections during the 2007 foot-and-mouth disease outbreak,http://dx.doi.org/10.1098/rsif.2008.0433,PMC2817150,,,"Active disease surveillance during epidemics is of utmost importance in detecting and eliminating new cases quickly, and targeting such surveillance to high-risk individuals is considered more efficient than applying a random strategy. Contact tracing has been used as a form of at-risk targeting, and a variety of mathematical models have indicated that it is likely to be highly efficient. However, for fast-moving epidemics, resource constraints limit the ability of the authorities to perform, and follow up, contact tracing effectively. As an alternative, we present a novel real-time Bayesian statistical methodology to determine currently undetected (occult) infections. For the UK foot-and-mouth disease (FMD) epidemic of 2007, we use real-time epidemic data synthesized with previous knowledge of FMD outbreaks in the UK to predict which premises might have been infected, but remained undetected, at any point during the outbreak. This provides both a framework for targeting surveillance in the face of limited resources and an indicator of the current severity and spatial extent of the epidemic. We anticipate that this methodology will be of substantial benefit in future outbreaks, providing a compromise between targeted manual surveillance and random or spatially targeted strategies.",,"['Jewell, C. P.', 'Keeling, M. J.', 'Roberts, G. O.']",,,,
,PMC,In This Issue,http://dx.doi.org/10.1073/iti05008105,PMC2604952,,,,,,,,,
,PMC,Growth of an RNA Virus in Single Cells Reveals a Broad Fitness Distribution,http://dx.doi.org/10.1016/j.virol.2008.10.031,PMC2666790,,,"Genetic and environmental factors will influence the growth of an RNA virus, but their relative contributions are challenging to resolve because standard culture methods mask how virus particles interact with individual host cells. Here, single particles of vesicular stomatitis virus, a prototype RNA virus, were used to infect individual BHK cells. Infected cells produced 50 to 8000 progeny virus particles, but these differences were lost upon subsequent culture, suggesting the diversity of yields reflected cell-to-cell differences rather than viral genetic variation. Cells infected at different phases of their cell cycle produced from 1400(early S) to 8700(G(2)M) infectious virus particles, coinciding with the middle-to-upper range of the observed distribution. Fluctuations in virus and cell compositions and noisy gene expression may also contribute to the broad distribution of virus yields. These findings take a step toward quantifying how environmental variation can impact the fitness distribution of a RNA virus.",,"['Zhu, Ying', 'Yongky, Andrew', 'Yin, John']",,,,
,PMC,Old and new faces of the nucleolus. Workshop on the Nucleolus and Disease,http://dx.doi.org/10.1038/embor.2008.230,PMC2613212,,,,,"['Stark, Lesley A', 'Taliansky, Michael']",,,,
,PMC,The Tumor Marker Human Placental Protein 11 Is an  Endoribonuclease,http://dx.doi.org/10.1074/jbc.M805759200,PMC3259861,,,"Human PP11 (placental protein 11) was previously described as a serine protease specifically expressed in the syncytiotrophoblast and in numerous tumor tissues. Several PP11-like proteins were annotated in distantly related organisms, such as worms and mammals, suggesting their involvement in evolutionarily conserved processes. Based on sequence similarity, human PP11 was included in a protein family whose characterized members are XendoU, a Xenopus laevis endoribonuclease involved in small nucleolar RNA processing, and Nsp15, an endoribonuclease essential for coronavirus replication. Here we show that the bacterially expressed human PP11 displays RNA binding capability and cleaves single stranded RNA in a Mn(2+)-dependent manner at uridylates, to produce molecules with 2′,3′-cyclic phosphate ends. These features, together with structural and mutagenesis analyses, which identified the potential active site residues, reveal striking parallels to the amphibian XendoU and assign a ribonuclease function to PP11. This newly discovered enzymatic activity places PP11-like proteins in a completely new perspective.",,"['Laneve, Pietro', 'Gioia, Ubaldo', 'Ragno, Rino', 'Altieri, Fabio', 'Di Franco, Carmen', 'Santini, Tiziana', 'Arceci, Massimo', 'Bozzoni, Irene', 'Caffarelli, Elisa']",,,,
,PMC,Another Piece of the Puzzle: Human Metapneumovirus Infections in Adults,http://dx.doi.org/10.1001/archinte.168.22.2489,PMC2783624,,,"BACKGROUND: Each winter respiratory viruses account for a significant proportion of serious respiratory illness, including hospitalization, in older adults and those with underlying medical conditions. We describe the incidence and clinical impact of human Metapneumovirus (hMPV), a newly identified virus, in adults. METHODS: hMPV infection was identified in three prospectively enrolled adult cohorts (young persons age 19-40, healthy adults ≥ 65 years, and high-risk adults) and a hospitalized cohort over 4 consecutive winters. The incidence and clinical impact was compared to influenza A and Respiratory Syncytial Virus infection in the same groups. RESULTS: Using reverse transcriptase-polymerase chain reaction (RT-PCR) and serology hMPV infection was identified in 2.2-10.5% of the three prospectively followed outpatient cohorts annually. Asymptomatic infection was common, accounting for at least 40% of infections in each of the cohorts. Symptoms, when they did occur, were typical of an upper respiratory illness although a few high-risk persons required hospitalization. Among 1386 hospitalized subjects, hMPV was identified in 8.5%, ranging from 4.3% to 13.2% depending upon the year. Dual viral infection was identified in 22.9%. Wheezing was frequent (80%) and more common than with influenza. Twelve percent required intensive care unit admission and 11% ventilatory support, rates similar to influenza and RSV infection. CONCLUSION: hMPV is a common infection in adults of all ages, and although often asymptomatic, can result in serious infection requiring hospitalization. Like influenza A and RSV, hMPV is also a major contributor to the burden of winter-time respiratory illnesses in older adults.",,"['Walsh, Edward E.', 'Peterson, Derick R.', 'Falsey, Ann R.']",,,,
,PMC,IFN-γ-mediated suppression of coronavirus replication in glial-committed progenitor cells,http://dx.doi.org/10.1016/j.virol.2008.10.036,PMC2779567,,,"The neurotropic JHM strain of mouse hepatitis virus (JHMV) replicates primarily within glial cells following intracranial inoculation of susceptible mice, with relative sparing of neurons. This study demonstrates that glial cells derived from neural progenitor cells are susceptible to JHMV infection and that treatment of infected cells with IFN-γ inhibits viral replication in a dose-dependent manner. Although type I IFN production is muted in JHMV-infected glial cultures, IFN-β is produced following IFN-γ-treatment of JHMV-infected cells. Also, direct treatment of infected glial cultures with recombinant mouse IFN-α or IFN-β inhibits viral replication. IFN-γ-mediated control of JHMV replication is dampened in glial cultures derived from the neural progenitor cells of type I receptor knock-out mice. These data indicate that JHMV is capable of infecting glial cells generated from neural progenitor cells and that IFN-γ-mediated control of viral replication is dependent, in part, on type I IFN secretion.",,"['Whitman, Lucia', 'Zhou, Haixia', 'Perlman, Stanley', 'Lane, Thomas E.']",,,,
,PMC,Proteasome Inhibitors Enhance Bacteriophage Lambda (λ) Mediated Gene Transfer in Mammalian Cells,http://dx.doi.org/10.1016/j.virol.2008.11.019,PMC2654414,,,"Bacteriophage lambda vectors can transfer their genomes into mammalian cells, resulting in expression of phage-encoded genes. However, this process is inefficient. Experiments were therefore conducted to delineate the rate limiting step(s) involved, using a phage vector that contains a mammalian luciferase reporter gene cassette. The efficiency of phage-mediated gene transfer in mammalian cells was quantitated, in the presence or absence of pharmacologic inhibitors of cell uptake and degradation pathways. Inhibitors of lysosomal proteases and proteasome inhibitors strongly enhanced phage-mediated luciferase expression, suggesting that these pathways contribute to the destruction of intracellular phage particles. In contrast, inhibition of endosome acidification had no effect on phage-mediated gene transfer, presumably because phage lambda is tolerant to extended exposure to low pH. These findings provide insights into the pathways by which phage vectors enter and transduce mammalian cells, and suggest that it may be possible to pharmacologically enhance the efficiency of phage-mediated gene transfer in mammalian cells. Finally, the data also suggest that the proteasome complex may serve as an innate defense mechanism that restricts the infection of mammalian cells by diverse viral agents.",,"['Volcy, Ketna', 'Dewhurst, Stephen']",,,,
,PMC,Human Airway Epithelial Cell Culture to Identify New Respiratory Viruses: Coronavirus NL63 as a Model,http://dx.doi.org/10.1016/j.jviromet.2008.10.022,PMC2671689,,,"Propagation of new human respiratory virus pathogens in established cell lines is hampered by a lack of predictability regarding cell line permissivity and by availability of suitable antibody reagents to detect infection in cell lines that do not exhibit significant cytopathic effect. Recently, molecular methods have been used to amplify and identify novel nucleic acid sequences directly from clinical samples, but these methods may be hampered by the quantity of virus present in respiratory secretions at different time points following the onset of infection. Human airway epithelial (HAE) cultures, which effectively mimic the human bronchial environment, allow for cultivation of a wide variety of human respiratory viral pathogens. The goal of the experiments described here was to determine if propagation and identification of a human respiratory virus may be achieved through inoculation of HAE cultures followed by whole transcriptome amplification (WTA) and sequence analysis. To establish proof-of-principle human coronavirus NL63 (HCoV-NL63) was evaluated, and the first visualization of HCoV-NL63 virus by transmission electron microscopy (TEM) is reported. Initial propagation of human respiratory secretions onto HAE cultures followed by TEM and WTA of culture supernatant may be a useful approach for visualization and detection of new human respiratory pathogens that have eluded identification by traditional approaches.",,"['Banach, Bridget', 'Orenstein, Jan M.', 'Fox, Linda M.', 'Randell, Scott H.', 'Rowley, Anne H.', 'Baker, Susan C.']",,,,
,PMC,"A single-amino acid substitution in West Nile virus 2K peptide between NS4A and NS4B confers resistance to lycorine, a flavivirus inhibitor",http://dx.doi.org/10.1016/j.virol.2008.11.003,PMC5388927,,,"Lycorine potently inhibits flaviviruses in cell culture. At 1.2-μM concentration, lycorine reduced viral titers of West Nile (WNV), dengue, and yellow fever viruses by 10(2)- to 10(4)-fold. However, the compound did not inhibit an alphavirus (Western equine encephalitis virus) or a rhabdovirus (vesicular stomatitis virus), indicating a selective antiviral spectrum. The compound exerts its antiviral activity mainly through suppression of viral RNA replication. A Val→Met substitution at the 9th amino acid position of the viral 2K peptide (spanning the endoplasmic reticulum membrane between NS4A and NS4B proteins) confers WNV resistance to lycorine, through enhancement of viral RNA replication. Initial chemistry synthesis demonstrated that modifications of the two hydroxyl groups of lycorine can increase the compound’s potency, while reducing its cytotoxicity. Taken together, the results have established lycorine as a flavivirus inhibitor for antiviral development. The lycorine-resistance results demonstrate a direct role of the 2K peptide in flavivirus RNA synthesis.",,"['Zou, Gang', 'Puig-Basagoiti, Francesc', 'Zhang, Bo', 'Qing, Min', 'Chen, Liqiang', 'Pankiewicz, Krzysztof W.', 'Felczak, Krzysztof', 'Yuan, Zhiming', 'Shi, Pei-Yong']",,,,
,PMC,Novel Influenza Virus NS1 Antagonists Block Replication and Restore Innate Immune Function,http://dx.doi.org/10.1128/JVI.01805-08,PMC2643796,,,"The innate immune system guards against virus infection through a variety of mechanisms including mobilization of the host interferon system, which attacks viral products mainly at a posttranscriptional level. The influenza virus NS1 protein is a multifunctional facilitator of virus replication, one of whose actions is to antagonize the interferon response. Since NS1 is required for efficient virus replication, it was reasoned that chemical inhibitors of this protein could be used to further understand virus-host interactions and also serve as potential new antiviral agents. A yeast-based assay was developed to identify compounds that phenotypically suppress NS1 function. Several such compounds exhibited significant activity specifically against influenza A virus in cell culture but had no effect on the replication of another RNA virus, respiratory syncytial virus. Interestingly, cells lacking an interferon response were drug resistant, suggesting that the compounds block interactions between NS1 and the interferon system. Accordingly, the compounds reversed the inhibition of beta interferon mRNA induction during infection, which is known to be caused by NS1. In addition, the compounds blocked the ability of NS1 protein to inhibit double-stranded RNA-dependent activation of a transfected beta interferon promoter construct. The effects of the compounds were specific to NS1, because they had no effect on the ability of the severe acute respiratory syndrome coronavirus papainlike protease protein to block beta interferon promoter activation. These data demonstrate that the function of NS1 can be modulated by chemical inhibitors and that such inhibitors will be useful as probes of biological function and as starting points for clinical drug development.",,"['Basu, Dipanwita', 'Walkiewicz, Marcin P.', 'Frieman, Matthew', 'Baric, Ralph S.', 'Auble, David T.', 'Engel, Daniel A.']",,,,
,PMC,Nuclear Magnetic Resonance Structure Shows that the Severe Acute Respiratory Syndrome Coronavirus-Unique Domain Contains a Macrodomain Fold,http://dx.doi.org/10.1128/JVI.01781-08,PMC2643772,,,"The nuclear magnetic resonance (NMR) structure of a central segment of the previously annotated severe acute respiratory syndrome (SARS)-unique domain (SUD-M, for “middle of the SARS-unique domain”) in SARS coronavirus (SARS-CoV) nonstructural protein 3 (nsp3) has been determined. SUD-M(513-651) exhibits a macrodomain fold containing the nsp3 residues 528 to 648, and there is a flexibly extended N-terminal tail with the residues 513 to 527 and a C-terminal flexible tail of residues 649 to 651. As a follow-up to this initial result, we also solved the structure of a construct representing only the globular domain of residues 527 to 651 [SUD-M(527-651)]. NMR chemical shift perturbation experiments showed that SUD-M(527-651) binds single-stranded poly(A) and identified the contact area with this RNA on the protein surface, and electrophoretic mobility shift assays then confirmed that SUD-M has higher affinity for purine bases than for pyrimidine bases. In a further search for clues to the function, we found that SUD-M(527-651) has the closest three-dimensional structure homology with another domain of nsp3, the ADP-ribose-1""-phosphatase nsp3b, although the two proteins share only 5% sequence identity in the homologous sequence regions. SUD-M(527-651) also shows three-dimensional structure homology with several helicases and nucleoside triphosphate-binding proteins, but it does not contain the motifs of catalytic residues found in these structural homologues. The combined results from NMR screening of potential substrates and the structure-based homology studies now form a basis for more focused investigations on the role of the SARS-unique domain in viral infection.",,"['Chatterjee, Amarnath', 'Johnson, Margaret A.', 'Serrano, Pedro', 'Pedrini, Bill', 'Joseph, Jeremiah S.', 'Neuman, Benjamin W.', 'Saikatendu, Kumar', 'Buchmeier, Michael J.', 'Kuhn, Peter', 'Wüthrich, Kurt']",,,,
,PMC,Multiple Nucleic Acid Binding Sites and Intrinsic Disorder of Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein: Implications for Ribonucleocapsid Protein Packaging,http://dx.doi.org/10.1128/JVI.02001-08,PMC2643731,,,"The nucleocapsid protein (N) of the severe acute respiratory syndrome coronavirus (SARS-CoV) packages the viral genomic RNA and is crucial for viability. However, the RNA-binding mechanism is poorly understood. We have shown previously that the N protein contains two structural domains—the N-terminal domain (NTD; residues 45 to 181) and the C-terminal dimerization domain (CTD; residues 248 to 365)—flanked by long stretches of disordered regions accounting for almost half of the entire sequence. Small-angle X-ray scattering data show that the protein is in an extended conformation and that the two structural domains of the SARS-CoV N protein are far apart. Both the NTD and the CTD have been shown to bind RNA. Here we show that all disordered regions are also capable of binding to RNA. Constructs containing multiple RNA-binding regions showed Hill coefficients greater than 1, suggesting that the N protein binds to RNA cooperatively. The effect can be explained by the “coupled-allostery” model, devised to explain the allosteric effect in a multidomain regulatory system. Although the N proteins of different coronaviruses share very low sequence homology, the physicochemical features described above may be conserved across different groups of Coronaviridae. The current results underscore the important roles of multisite nucleic acid binding and intrinsic disorder in N protein function and RNP packaging.",,"['Chang, Chung-Ke', 'Hsu, Yen-Lan', 'Chang, Yuan-Hsiang', 'Chao, Fa-An', 'Wu, Ming-Chya', 'Huang, Yu-Shan', 'Hu, Chin-Kun', 'Huang, Tai-Huang']",,,,
,PMC,Searching immunodominant epitopes prior to epidemic: HLA class II-restricted SARS-CoV spike protein epitopes in unexposed individuals,http://dx.doi.org/10.1093/intimm/dxn124,PMC2638843,,,"Identification of dominant T cell epitopes within newly emerging and re-emerging infectious organisms is valuable in understanding pathogenic immune responses and potential vaccine designs. However, difficulties in obtaining samples from patients or convalescent subjects have hampered research in this direction. We demonstrated a strategy, tetramer-guided epitope mapping, that specific CD4+ T cell epitopes can be identified by using PBMC from subjects that have not been exposed to the infectious organism. Sixteen HLA-DR0401- and 14 HLA-DR0701-restricted epitopes within spike protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) were identified. Among these, spike protein residues 159–171, 166–178, 449–461 and 1083–1097 were identified to contain naturally processed immunodominant epitopes based on strong in vitro T cell responses of PBMC (as assayed by tetramer staining) to intact spike protein stimulation. These immunodominant epitopes were confirmed in vivo in HLA-DR0401 transgenic mice by immunizing with spike protein. Furthermore, the epitope-specific T cells from naive donors secreted IFN-γ and IL-13 upon re-stimulation with corresponding tetramers. Our study demonstrates a strategy to determine potential immunodominant epitopes for emerging infectious pathogens prior to their epidemic circulation.",,"['Yang, Junbao', 'James, Eddie', 'Roti, Michelle', 'Huston, Laurie', 'Gebe, John A.', 'Kwok, William W.']",,,,
,PMC,Crystal structures of the X-domains of a Group-1 and a Group-3 coronavirus reveal that ADP-ribose-binding may not be a conserved property,http://dx.doi.org/10.1002/pro.15,PMC2708038,,,"The polyproteins of coronaviruses are cleaved by viral proteases into at least 15 nonstructural proteins (Nsps). Consisting of five domains, Nsp3 is the largest of these (180–210 kDa). Among these domains, the so-called X-domain is believed to act as ADP-ribose-1″-phosphate phosphatase or to bind poly(ADP-ribose). However, here we show that the X-domain of Infectious Bronchitis Virus (strain Beaudette), a Group-3 coronavirus, fails to bind ADP-ribose. This is explained on the basis of the crystal structure of the protein, determined at two different pH values. For comparison, we also describe the crystal structure of the homologous X-domain from Human Coronavirus 229E, a Group-1 coronavirus, which does bind ADP-ribose.",,"['Piotrowski, Yvonne', 'Hansen, Guido', 'Boomaars-van der Zanden, A Linda', 'Snijder, Eric J', 'Gorbalenya, Alexander E', 'Hilgenfeld, Rolf']",,,,
,PMC,Immunity from Smallpox Vaccine Persists for Decades: A Longitudinal Study,http://dx.doi.org/10.1016/j.amjmed.2008.08.019,PMC2610468,,,"PURPOSE: The threat of smallpox resulting from bioterrorist action has prompted a reassessment of the level of immunity in current populations. METHODS: We have examined the magnitude and duration of antiviral antibody immunity conferred by smallpox vaccination in 246 participants of the Baltimore Longitudinal Study of Aging. Of this population, 209 subjects were vaccinated one or more times 13 to 88 years before this evaluation, and stored serum samples were available at various intervals after vaccination. An additional 8 subjects who had documented childhood smallpox infection and 29 subjects with no history of infection or vaccination were included. We quantified the total vaccinia IgG and neutralizing antibody titers in each of these subgroups of participants over time. RESULTS: Vaccinated participants maintained antivaccinia IgG and neutralizing antibody titers above 3 natural logs essentially indefinitely. The absolute titer of antivaccinia antibody was only slightly higher after multiple vaccinations. In 97% of the participants, no decrease in vaccinia-specific antibody titers was noted with age over a follow-up period of up to 88 years. Moreover, Baltimore Longitudinal Study of Aging participants who survived active smallpox infections in their youth retained antivaccinia antibody titers that were similar to the levels detected in vaccinated subjects. CONCLUSION: These data suggest that multiple or recent vaccinations are not essential to maintain vaccinia-specific antibody responses in human subjects. Scarce vaccine supplies should be applied first to individuals who have not previously been vaccinated.",,"['Taub, Dennis D.', 'Ershler, William B.', 'Janowski, Mark', 'Artz, Andrew', 'Key, Michael L.', 'McKelvey, Julie', 'Muller, Denis', 'Moss, Bernard', 'Ferrucci, Luigi', 'Duffey, Patricia L.', 'Longo, Dan L.']",,,,
,PMC,Communicating With the Public About Emerging Health Threats: Lessons From the Pre-Event Message Development Project,http://dx.doi.org/10.2105/AJPH.2006.107102,PMC2636543,,,"Objectives. We sought to better understand the challenges of communicating with the public about emerging health threats, particularly threats involving toxic chemicals, biological agents, and radioactive materials. Methods. At the request of the Centers for Disease Control and Prevention, we formed an interdisciplinary consortium of investigative teams from 4 schools of public health. Over 2 years, the investigative teams conducted 79 focus group interviews with 884 participants and individual cognitive response interviews with 129 respondents, for a total sample of 1013 individuals. The investigative teams systematically compared their results with other published research in public health, risk communication, and emergency preparedness. Results. We found limited public understanding of emerging biological, chemical, and radioactive materials threats and of the differences between them; demand for concrete, accurate, and consistent information about actions needed for protection of self and family; active information seeking from media, local authorities, and selected national sources; and areas in which current emergency messaging can be improved. Conclusions. The public will respond to a threat situation by seeking protective information and taking self-protective action, underlining the critical role of effective communication in public health emergencies.",,"['Wray, Ricardo J.', 'Becker, Steven M.', 'Henderson, Neil', 'Glik, Deborah', 'Jupka, Keri', 'Middleton, Sarah', 'Henderson, Carson', 'Drury, Allison', 'Mitchell, Elizabeth W.']",,,,
,PMC,Veterinary medicine and public health,,PMC2583410,,,,,"Gyles, Carlton",,,,
,PMC,Murine Norovirus: An Intercurrent Variable in a Mouse Model of Bacteria-Induced Inflammatory Bowel Disease,,PMC2710753,,,"Murine norovirus (MNV) has recently been recognized as a widely prevalent viral pathogen in mouse colonies and causes disease and mortality in mice with impaired innate immunity. We tested the hypothesis that MNV infection would alter disease course and immune responses in mice with inflammatory bowel disease (IBD). FVB.129P2-Abcb1a(tm1Bor) N7 (Mdr1a−/−) mice develop spontaneous IBD that is accelerated by infection with Helicobacter bilis. As compared with controls, Mdr1a−/− mice coinfected with MNV4 and H. bilis showed greater weight loss and IBD scores indicative of severe colitis, demonstrating that MNV4 can modulate the progression of IBD. Compared with controls, mice inoculated with MNV4 alone had altered levels of serum biomarkers, and flow cytometric analysis of immune cells from MNV4-infected mice showed changes in both dendritic cell (CD11c(+)) and other nonT cell (CD4(−) CD8(−)) populations. Dendritic cells isolated from MNV4-infected mice induced higher IFNγ production by polyclonal T cells in vitro at 2 d after infection but not at later time points, indicating that MNV4 infection enhances antigen presentation by dendritic cells early after acute infection. These findings indicate that acute infection with MNV4 is immunomodulatory and alters disease progression in a mouse model of IBD.",,"['Lencioni, Karen Chase', 'Seamons, Audrey', 'Treuting, Piper M', 'Maggio-Price, Lillian', 'Brabb, Thea']",,,,
,PMC,Protein biomarkers in cancer: Natural glycoprotein microarray approaches,,PMC2920894,,,"Protein glycosylation is the most versatile and common protein modification and plays important roles in various biological processes and disease progression. In this review, the development of microarray technology for protein glycosylation analysis is described. Three types are discussed: carbohydrate, lectin and natural glycoprotein microarrays. The advantages of microarray technology to study protein glycosylation are high-volume throughput coupled with a highly miniaturized platform. These techniques show great promise for detecting interactions that involve carbohydrates and as a screening tool to detect glycan patterns important for the early diagnosis of disease.",,"['Zhao, Jia', 'Patwa, Tasneem H', 'Lubman, David M', 'Simeone, Diane M']",,,,
,PMC,Alterations in Circulatory and Renal Angiotensin-Converting Enzyme and Angiotensin-Converting Enzyme 2 in Fetal Programmed Hypertension,http://dx.doi.org/10.1161/HYPERTENSIONAHA.108.124339,PMC2674380,,,"Antenatal betamethasone treatment is a widely accepted therapy to accelerate lung development and improve survival in preterm infants. However, there are reports that infants who receive antenatal glucocorticoids exhibit higher systolic blood pressure in their early adolescent years. We have developed an experimental model of programming whereby the offspring of pregnant sheep administered clinically relevant doses of betamethasone exhibit elevated blood pressure. We tested the hypothesis as to whether alterations in angiotensin-converting enzyme (ACE), ACE2, and neprilysin in serum, urine, and proximal tubules are associated with this increase in mean arterial pressure. Male sheep were administered betamethasone (2 doses of 0.17 mg/kg, 24 hours apart) or vehicle at the 80th day of gestation and delivered at term. Sheep were instrumented at adulthood (1.8 years) for direct conscious recording of mean arterial pressure. Serum and urine were collected and proximal tubules isolated from the renal cortex. Betamethasone-treated animals had elevated mean arterial pressure (97±3 versus 83±2 mm Hg; P<0.05) and a 25% increase in serum ACE activity (48.4±7.0 versus 36.0±2.7 fmol/mL per minute) but a 40% reduction in serum ACE2 activity (18.8±1.2 versus 31.4±4.4 fmol/mL per minute). In isolated proximal tubules, ACE2 activity and expression were 50% lower in the treated sheep with no significant change in ACE or neprilysin activities. We conclude that antenatal steroid treatment results in the chronic alteration of ACE and ACE2 in the circulatory and tubular compartments, which may contribute to the higher blood pressure in this model of fetal programming-induced hypertension.",,"['Shaltout, Hossam A.', 'Figueroa, Jorge P.', 'Rose, James C.', 'Diz, Debra I.', 'Chappell, Mark C.']",,,,
,PMC,CD66a (CEACAM1) expression by mouse natural killer cells,http://dx.doi.org/10.1111/j.1365-2567.2008.02867.x,PMC2612550,,,"CD66a (CEACAM1), an adhesion molecule that has regulatory function on T lymphocytes, was found to be expressed on a minority of mouse natural killer (NK) cells, especially in the liver. CD66a expression on NK cells depended on their differentiation stage, with highest levels on immature CD49b(−)NK cells. Expression of CD66a on NK cells was strongly enhanced by in vitro activation with interleukin-12 (IL-12) and IL-18. However, in vivo NK cell stimulation by infection with lactate dehydrogenase-elevating virus did not lead to strong CD66a expression, even on activated interferon--γ-producing NK cells. These results indicate that CD66a expression is differently regulated, depending on the NK cell activation pathway, which may lead to distinct regulatory mechanisms of the functional subpopulations of these cells.",,"['Thirion, Gaëtan', 'Feliu, Ana Agusti', 'Coutelier, Jean-Paul']",,,,
,PMC,Emerging and Zoonotic Infections in Women,http://dx.doi.org/10.1016/j.idc.2008.05.007,PMC2650502,,,"Emerging infections, many of them zoonotic, are caused by a wide variety of pathogens with global distribution. Their impact on women is similarly diverse. Pathogens that were previously rare are emerging in recent years to cause disease in new populations, and global travel facilitates their rapid spread across continents. Finally, human encroachment on previously remote areas has brought people into contact with zoonotic diseases and vectors never before characterized. Although systematic study of rare outbreaks can be challenging, our knowledge of emerging pathogens and their differential effects on women, including those who are pregnant, has started to accumulate. We discuss the effects on women of lymphocytic choriomeningitis virus, West Nile virus, SARS coronavirus, avian influenza A (H5N1), virus, and the viral hemorrhagic fevers. We also explore the spirochetal illnesses and Chagas disease as they pertain to the pregnant patient. Finally, we review the potential impact of candidate bioterror agents on the female population, and address related issues of prophylaxis and therapy.",,"['Theiler, Regan N.', 'Rasmussen, Sonja A.', 'Treadwell, Tracee A.', 'Jamieson, Denise J.']",,,,
,PMC,Enhanced T cell apoptosis within Drak2-deficient mice promotes resistance to autoimmunity,,PMC2709975,,,"Clonal expansion of T cells is vital to adaptive immunity, yet this process must be tightly controlled to prevent autoimmune disease. The serine/threonine kinase DRAK2 is a negative regulator of T cell receptor (TCR) signaling and sets the threshold for the activation of naïve and memory T cells, and selected thymocytes. Despite enhanced T cell activation, Drak2−/− mice are resistant to experimental autoimmune encephalomyelitis (EAE), an autoimmune demyelinating disease that resembles multiple sclerosis. However, the basis for this autoimmune resistance is currently unknown. Here we show that, in the absence of DRAK2 signaling, T cells require greater tonic signaling for maintenance during clonal expansion. Following stimulation, Drak2−/− T cells were more sensitive to an intrinsic form of apoptosis that was prevented by CD28 ligation, homeostatic cytokines, or enforced Bcl-xL expression. T cell-specific Bcl-xL expression also restored the susceptibility of Drak2−/− mice to EAE and enhanced thymic positive selection. These findings demonstrate that DRAK2 is selectively important for T cell survival and highlight the potential that DRAK2 blockade may lead to permanent autoimmune T cell destruction via intrinsic apoptosis pathways.",,"['Ramos, Stephanie J.', 'Hernandez, Jeniffer B.', 'Gatzka, Martina', 'Walsh, Craig M.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.02125-08,PMC2583642,,,,,,,,,
,PMC,Mechanisms of Severe Acute Respiratory Syndrome Pathogenesis and Innate Immunomodulation,http://dx.doi.org/10.1128/MMBR.00015-08,PMC2593566,,,"Summary: The modulation of the immune response is a common practice of many highly pathogenic viruses. The emergence of the highly pathogenic coronavirus severe acute respiratory virus (SARS-CoV) serves as a robust model system to elucidate the virus-host interactions that mediate severe end-stage lung disease in humans and animals. Coronaviruses encode the largest positive-sense RNA genome of ∼30 kb, encode a variety of replicase and accessory open reading frames that are structurally unique, and encode novel enzymatic functions among RNA viruses. These viruses have broad or specific host ranges, suggesting the possibility of novel strategies for targeting and regulating host innate immune responses following virus infection. Using SARS-CoV as a model, we review the current literature on the ability of coronaviruses to interact with and modify the host intracellular environment during infection. These studies are revealing a rich set of novel viral proteins that engage, modify, and/or disrupt host cell signaling and nuclear import machinery for the benefit of virus replication.",,"['Frieman, Matthew', 'Baric, Ralph']",,,,
,PMC,Development of an Enzyme-Linked Immunosorbent Assay-Based Test with a Cocktail of Nucleocapsid and Spike Proteins for Detection of Severe Acute Respiratory Syndrome-Associated Coronavirus-Specific Antibody,http://dx.doi.org/10.1128/CVI.00252-08,PMC2643541,,,"A new enzyme-linked immunosorbent assay (ELISA)-based immunoglobulin G (IgG)-plus-IgM antibody detection test for severe acute respiratory syndrome (SARS) has been developed by using a cocktail of four recombinant polypeptides as the antigen. These recombinant fragments were designed as parts of two different structural proteins from SARS-associated coronavirus (SARS-CoV). One recombinant polypeptide, S251-683, was designed as part of the spike glycoprotein, and the other three polypeptides comprised almost the whole nucleocapsid protein, avoiding the last 25 C-terminal amino acids. Immunization with a cocktail of these four polypeptides yielded a specific polyclonal antibody that is able to recognize SARS-CoV-infected cells by an immunofluorescence assay. This polypeptide cocktail was also used to set up an ELISA-based IgG-plus-IgM antibody detection test, which showed 99% specificity and 90% sensitivity upon evaluation using sera from 100 healthy negative controls and 20 SARS patients. Separate immunoreactivity assays with each recombinant polypeptide demonstrated that a combination of N and S protein fragments was more suitable than the individual peptides for developing a serological assay for SARS-CoV.",,"['Giménez, Luis G.', 'Rojas, Jose', 'Rojas, Almudena', 'Mendoza, Joaquín', 'Camacho, Ana G.']",,,,
,PMC,Post-transcriptional silencing of CCR3 downregulates IL-4 stimulated release of eotaxin-3 (CCL26) and other CCR3 ligands in alveolar type II cells,http://dx.doi.org/10.1016/j.cyto.2008.09.006,PMC2661111,,,"Trafficking and inflammation in airway diseases are, in part, modulated by members of the CC chemokine family, eotaxin-1 (CCL11), eotaxin-2 (CCL24), and eotaxin-3 (CCL26), which transduce signals through their CCR3 receptor. In this context, we hypothesized that transfecting alveolar type II epithelial cells with CCR3-targeted siRNA or antisense (AS-ODN) sequences will downregulate cellular synthesis and release of the primary CCR3 ligands CCL26 and CCL24 and will modulate other CCR3 ligands. The human A549 alveolar type II epithelium-like cell culture model was used for transfection and subsequent effects on CCR3 agonists. siRNAs were particularly effective. PCR showed a 60-80% decrease in mRNA and immunoblots showed up to 75-84% reduction of CCR3 in siRNA treated cells. CCR3-siRNA treatments reduced IL-4 stimulated CCL26 release and constitutive CCL24 release by 65% and 80%, respectively. Release of four additional CCR3 agonists RANTES, MCP-2, MCP-3 and MCP-4 was also significantly reduced by CCR3-siRNA treatments of the alveolar type II cells. Activation of eosinophils, assessed as superoxide anion generation, was reduced when eosinophils were treated with supernatants of A549 cells pretreated with CCR3-targeted siRNAs or AS-ODNs. Collectively, the data suggest that post-transcriptional regulation of CCR3 receptors may be a potential therapeutic approach for interrupting proinflammatory signaling.",,"['Taka, Equar', 'Errahali, Younes J.', 'Abonyo, Barack O.', 'Bauer, David M.', 'Heiman, Ann S.']",,,,
,PMC,The Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions,http://dx.doi.org/10.1128/JVI.02046-08,PMC2643787,,,"The human immunodeficiency virus type 1 (HIV-1) envelope spike is a heavily glycosylated trimeric structure in which protein surfaces conserved between different HIV-1 isolates are particularly well hidden from antibody recognition. However, even variable regions on the spike tend to be less antigenic and immunogenic than one might have anticipated for external structures. Here we show that the envelope spike of primary viruses has an ability to restrict antibody recognition of variable regions. We show that access to an artificial epitope, introduced at multiple positions across the spike, is frequently limited, even though the epitope has been inserted at surface-exposed regions on the spike. Based on the data, we posit that restricted antibody access may be the result, at least in part, of a rigidification of the epitope sequence in the context of the spike and/or a highly effective flexible arrangement of the glycan shield on primary viruses. Evolution of the HIV envelope structure to incorporate extra polypeptide sequences into nominally accessible regions with limited antibody recognition may contribute to reducing the magnitude of antibody responses during infection and allow the virus to replicate unhindered by antibody pressure for longer periods.",,"['Pantophlet, Ralph', 'Wang, Meng', 'Aguilar-Sino, Rowena O.', 'Burton, Dennis R.']",,,,
,PMC,Recombinant Canine Coronaviruses Related to Transmissible Gastroenteritis Virus of Swine Are Circulating in Dogs,http://dx.doi.org/10.1128/JVI.01937-08,PMC2620906,,,"Four canine coronavirus type II (CCoV-II) strains were identified in the guts and internal organs of pups which had died of acute gastroenteritis. The CCoV-II strains were strictly related to porcine transmissible gastroenteritis virus (TGEV) in the N-terminal domain of the spike protein, whereas in the other parts of the genome, a higher genetic relatedness to recent CCoV-II isolates was observed. Experimental infection of dogs with a TGEV-like isolate induced mild gastroenteritis without any systemic involvement. By virus neutralization tests, antigenic differences between reference and TGEV-like CCoVs were found. Our data support the potential recombinant origin of the TGEV-like CCoVs.",,"['Decaro, Nicola', 'Mari, Viviana', 'Campolo, Marco', 'Lorusso, Alessio', 'Camero, Michele', 'Elia, Gabriella', 'Martella, Vito', 'Cordioli, Paolo', 'Enjuanes, Luis', 'Buonavoglia, Canio']",,,,
,PMC,Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice,http://dx.doi.org/10.1073/pnas.0808116105,PMC2588415,,,"Defining prospective pathways by which zoonoses evolve and emerge as human pathogens is critical for anticipating and controlling both natural and deliberate pandemics. However, predicting tenable pathways of animal-to-human movement has been hindered by challenges in identifying reservoir species, cultivating zoonotic organisms in culture, and isolating full-length genomes for cloning and genetic studies. The ability to design and recover pathogens reconstituted from synthesized cDNAs has the potential to overcome these obstacles by allowing studies of replication and pathogenesis without identification of reservoir species or cultivation of primary isolates. Here, we report the design, synthesis, and recovery of the largest synthetic replicating life form, a 29.7-kb bat severe acute respiratory syndrome (SARS)-like coronavirus (Bat-SCoV), a likely progenitor to the SARS-CoV epidemic. To test a possible route of emergence from the noncultivable Bat-SCoV to human SARS-CoV, we designed a consensus Bat-SCoV genome and replaced the Bat-SCoV Spike receptor-binding domain (RBD) with the SARS-CoV RBD (Bat-SRBD). Bat-SRBD was infectious in cell culture and in mice and was efficiently neutralized by antibodies specific for both bat and human CoV Spike proteins. Rational design, synthesis, and recovery of hypothetical recombinant viruses can be used to investigate mechanisms of transspecies movement of zoonoses and has great potential to aid in rapid public health responses to known or predicted emerging microbial threats.",,"['Becker, Michelle M.', 'Graham, Rachel L.', 'Donaldson, Eric F.', 'Rockx, Barry', 'Sims, Amy C.', 'Sheahan, Timothy', 'Pickles, Raymond J.', 'Corti, Davide', 'Johnston, Robert E.', 'Baric, Ralph S.', 'Denison, Mark R.']",,,,
,PMC,A highly prevalent and genetically diversified Picornaviridae genus in South Asian children,http://dx.doi.org/10.1073/pnas.0807979105,PMC2629322,,,"Viral metagenomics focused on particle-protected nucleic acids was used on the stools of South Asian children with nonpolio acute flaccid paralysis (AFP). We identified sequences distantly related to Seneca Valley virus and cardioviruses that were then used as genetic footholds to characterize multiple viral species within a previously unreported genus of the Picornaviridae family. The picornaviruses were detected in the stools of >40% of AFP and healthy Pakistani children. A genetically diverse and highly prevalent enteric viral infection, characteristics similar to the Enterovirus genus, was therefore identified substantially expanding the genetic diversity of the RNA viral flora commonly found in children.",,"['Kapoor, Amit', 'Victoria, Joseph', 'Simmonds, Peter', 'Slikas, Elizabeth', 'Chieochansin, Thaweesak', 'Naeem, Asif', 'Shaukat, Shahzad', 'Sharif, Salmaan', 'Alam, Muhammad Masroor', 'Angez, Mehar', 'Wang, Chunlin', 'Shafer, Robert W.', 'Zaidi, Sohail', 'Delwart, Eric']",,,,
,PMC,Hantaan Virus Nucleocapsid Protein Binds to Importin α Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced Activation of Nuclear Factor Kappa B,http://dx.doi.org/10.1128/JVI.00986-08,PMC2620888,,,"Hantaviruses such as Hantaan virus (HTNV) and Andes virus cause two human diseases, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome, respectively. For both, disease pathogenesis is thought to be immunologically mediated and there have been numerous reports of patients with elevated levels of proinflammatory and inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), in their sera. Multiple viruses have developed evasion strategies to circumvent the host cell inflammatory process, with one of the most prevalent being the disruption of nuclear factor kappa B (NF-κB) activation. We hypothesized that hantaviruses might also moderate host inflammation by interfering with this pathway. We report here that the nucleocapsid (N) protein of HTNV was able to inhibit TNF-α-induced activation of NF-κB, as measured by a reporter assay, and the activation of endogenous p65, an NF-κB subunit. Surprisingly, there was no defect in the degradation of the inhibitor of NF-κB (IκB) protein, nor was there any alteration in the level of p65 expression in HTNV N-expressing cells. However, immunofluorescence antibody staining demonstrated that cells expressing HTNV N protein and a green fluorescent protein-p65 fusion had limited p65 nuclear translocation. Furthermore, we were able to detect an interaction between HTNV N protein and importin α, a nuclear import molecule responsible for shuttling NF-κB to the nucleus. Collectively, our data suggest that HTNV N protein can sequester NF-κB in the cytoplasm, thus inhibiting NF-κB activity. These findings, which were obtained using cells transfected with cDNA representing the HTNV N gene, were confirmed using HTNV-infected cells.",,"['Taylor, Shannon L.', 'Frias-Staheli, Natalia', 'García-Sastre, Adolfo', 'Schmaljohn, Connie S.']",,,,
,PMC,Serum Albumin Concentration and Waiting List Mortality in Idiopathic Interstitial Pneumonia,http://dx.doi.org/10.1378/chest.08-0754,PMC2666778,,,"BACKGROUND: Hypoalbuminemia is a reliable predictor of mortality in patients with various illnesses as well as a predictor of disability and mortality in healthy older adults. The association between hypoalbuminemia and mortality in patients with idiopathic interstitial pneumonia remains unknown. The objective of this study was to examine the relationship between serum albumin concentration and mortality in a large cohort of patients with idiopathic interstitial pneumonia listed for lung transplantation. METHODS: In patients classified as having idiopathic pulmonary fibrosis, who were listed for lung transplantation with the United Network for Organ Sharing between January 1, 2004, and December 31, 2006 (N=1,269), we studied the relationship between serum albumin concentration at the time of listing and mortality while awaiting transplantation. RESULTS: Lower serum albumin was associated with increased mortality rate. Patients in lower categories of serum albumin had increased mortality rates before and after multivariable adjustment (p value for linear trend < 0.0001). Analysis with serum albumin as a continuous predictor indicated that the mortality rate increased by 54% with each 0.5 g/dL decrease in serum albumin concentration (95% confidence interval: 32% to 79%). CONCLUSIONS: Lower serum albumin is strongly and independently associated with higher transplant-waiting list mortality in patients with idiopathic interstitial pneumonia.",,"['Zisman, David A.', 'Kawut, Steven M.', 'Lederer, David J.', 'Belperio, John A.', 'Lynch, Joseph P.', 'Schwarz, Marvin I.', 'Tayek, John A.', 'Reuben, David B.', 'Karlamangla, Arun S.']",,,,
,PMC,Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge,http://dx.doi.org/10.1016/j.virol.2008.09.030,PMC2649782,,,"We generated a new live-attenuated vaccine against Ebola virus (EBOV) based on a chimeric virus HPIV3/ΔF-HN/EboGP that contains the EBOV glycoprotein (GP) as the sole transmembrane envelope protein combined with the internal proteins of human parainfluenza virus type 3 (HPIV3). Electron microscopy analysis of the virus particles showed that they have an envelope and surface spikes resembling those of EBOV and a particle size and shape resembling those of HPIV3. When HPIV3/ΔF-HN/EboGP was inoculated via apical surface of an in vitro model of human ciliated airway epithelium, the virus was released from the apical surface; when applied to basolateral surface, the virus infected basolateral cells but did not spread through the tissue. Following intranasal (IN) inoculation of guinea pigs, scattered infected cells were detected in the lungs by immunohistochemistry, but infectious HPIV3/ΔF-HN/EboGP could not be recovered from the lungs, blood, or other tissues. Despite the attenuation, the virus was highly immunogenic, and a single IN dose completely protected the animals against a highly lethal intraperitoneal challenge of guinea pig-adapted EBOV.",,"['Bukreyev, Alexander', 'Marzi, Andrea', 'Feldmann, Friederike', 'Zhang, Liqun', 'Yang, Lijuan', 'Ward, Jerrold M.', 'Dorward, David W.', 'Pickles, Raymond J.', 'Murphy, Brian R.', 'Feldmann, Heinz', 'Collins, Peter L.']",,,,
,PMC,Dual Regulatory Roles of the Phosphatidylinositol 3-Kinase In Interferon Signaling,,PMC2597572,,,"The phosphatidylinositol (PI) 3-kinase is activated by the Type I and II interferon (IFN) receptors, but its precise role in the generation of IFN responses is not well understood. In the present study we used embryonic fibroblasts from mice with targeted disruption of the genes encoding for both the p85α and p85β regulatory subunits of PI3′ kinase (p85α-/-β-/-) to precisely define the role of the PI 3 kinase in the control of IFN-induced biological responses. Our data demonstrate that the PI 3 kinase plays dual regulatory roles in the induction of IFN-responses, by controlling both IFNα- and IFNγ- dependent transcriptional regulation of interferon sensitive genes (ISGs) and at the same time regulating the subsequent initiation of mRNA translation for such genes. This includes the Isg15, Cxcl10 and/or Irf7 genes, whose functions are important in the generation of the biological effects of IFNs. Consistent with this, the induction of IFN-antiviral responses is defective in double p85α/p85β knockout cells. Thus, integration of signals via the PI 3 kinase is a critical event during engagement of the IFN receptors that complements both the transcriptional activity of Jak-Stat pathways and controls initiation of mRNA translation.",,"['Kaur, Surinder', 'Sassano, Antonella', 'Joseph, Ajith M', 'Majchrzak-Kita, Beata', 'Eklund, Elizabeth A.', 'Verma, Amit', 'Brachmann, Saskia M.', 'Fish, Eleanor N.', 'Platanias, Leonidas C.']",,,,
,PMC,Atg5 is Essential for Cellular Immunity in vivo and recruitment of a p47 GTPase to the Toxoplasma gondii Parasitophorous Vacuole in Macrophages,http://dx.doi.org/10.1016/j.chom.2008.10.003,PMC2682425,,,"The physiologic importance of autophagy proteins for control of mammalian bacterial and parasitic infection in vivo is unknown. We show that expression of the essential autophagy protein Atg5 in granulocytes and macrophages is required for in vivo resistance to infection with L. monocytogenes and T. gondii. In primary macrophages, Atg5 was not required for IFNγ/LPS-mediated transcription, induction of nitric oxide, or inhibition of T. gondii replication. However, Atg5 was required for IFNγ/LPS-induced damage to the T. gondii parasitophorous vacuole membrane and parasite clearance. While we did not detect autophagosomes enveloping T. gondii, Atg5 was required for recruitment of the IFNγ-inducible p47 GTPase IIGP1 (Irga6) to the vacuole membrane. This work shows that Atg5 expression in phagocytic cells is essential for cellular immunity to intracellular pathogens in vivo and that an autophagy protein can participate in immunity and intracellular killing of pathogens via autophagosome-independent processes such as GTPase trafficking.",,"['Zhao, Zijiang', 'Fux, Blima', 'Goodwin, Megan', 'Dunay, Ildiko R.', 'Strong, David', 'Miller, Brian C.', 'Cadwell, Ken', 'Delgado-Vargas, Monica', 'Ponpuak, Marisa', 'Green, Karen G.', 'Schmidt, Robert E.', 'Mizushima, Noboru', 'Deretic, Vojo', 'Sibley, L. David', 'Virgin, Herbert W.']",,,,
,PMC,Severe Acute Respiratory Syndrome (SARS) Coronavirus-Induced Lung Epithelial Cytokines Exacerbate SARS Pathogenesis by Modulating Intrinsic Functions of Monocyte-Derived Macrophages and Dendritic Cells,http://dx.doi.org/10.1128/JVI.01792-08,PMC2655569,,,"Severe acute respiratory syndrome (SARS), which is caused by a novel coronavirus (CoV), is a highly communicable disease with the lungs as the major pathological target. Although SARS likely stems from overexuberant host inflammatory responses, the exact mechanism leading to the detrimental outcome in patients remains unknown. Pulmonary macrophages (Mφ), airway epithelium, and dendritic cells (DC) are key cellular elements of the host innate defenses against respiratory infections. While pulmonary Mφ are situated at the luminal epithelial surface, DC reside abundantly underneath the epithelium. Such strategic locations of these cells within the airways make it relevant to investigate their likely impact on SARS pathogenesis subsequent to their interaction with infected lung epithelial cells. To study this, we established highly polarized human lung epithelial Calu-3 cells by using the Transwell culture system. Here we report that supernatants harvested from the apical and basolateral domains of infected Calu-3 cells are potent in modulating the intrinsic functions of Mφ and DC, respectively. They prompted the production of cytokines by both Mφ and DC and selectively induced CD40 and CD86 expression only on DC. However, they compromised the abilities of the DC and Mφ in priming naïve T cells and phagocytosis, respectively. We also identified interleukin-6 (IL-6) and IL-8 as key SARS-CoV-induced epithelial cytokines capable of inhibiting the T-cell-priming ability of DC. Taken together, our results provide insights into the molecular and cellular bases of the host antiviral innate immunity within the lungs that eventually lead to an exacerbated inflammatory cascades and severe tissue damage in SARS patients.",,"['Yoshikawa, Tomoki', 'Hill, Terence', 'Li, Kui', 'Peters, Clarence J.', 'Tseng, Chien-Te K.']",,,,
,PMC,hnRNPs Relocalize to the Cytoplasm following Infection with Vesicular Stomatitis Virus,http://dx.doi.org/10.1128/JVI.01279-08,PMC2612367,,,"Vesicular stomatitis virus (VSV) matrix protein inhibits nuclear-cytoplasmic mRNA transport. The goal of this work is to determine whether VSV inhibits the nuclear-cytoplasmic transport of heterogeneous ribonucleoproteins (hnRNPs), which are thought to serve as mRNA export factors. Confocal microscopy experiments showed that hnRNPA1, hnRNPK, and hnRNPC1/C2, but not hnRNPB1 or lamin A/C, are relocalized to the cytoplasm during VSV infection. We determined whether protein import is inhibited by VSV by transfecting cells with a plasmid encoding enhanced green fluorescent protein (EGFP) tagged with either the M9 nuclear localization sequence (NLS) or the classical NLS. These experiments revealed that both the M9 NLS and the classical NLS are functional during VSV infection. These data suggest that the inhibition of protein import is not responsible for hnRNP relocalization during VSV infection but that hnRNP export is enhanced. We found that hnRNPA1 relocalization was significantly reduced following the silencing of the mRNA export factor Rae1, indicating that Rae1 is necessary for hnRNP export. In order to determine the role of hnRNPA1 in VSV infection, we silenced hnRNPA1 in HeLa cells and assayed three aspects of the viral life cycle: host protein synthesis shutoff concurrent with the onset of viral protein synthesis, replication by plaque assay, and cell killing. We observed that host shutoff and replication are unaffected by the reduction in hnRNPA1 but that the rate of VSV-induced apoptosis is slower in cells that have reduced hnRNPA1. These data suggest that VSV promotes hnRNPA1 relocalization in a Rae1-dependent manner for apoptotic signaling.",,"['Pettit Kneller, Elizabeth L.', 'Connor, John H.', 'Lyles, Douglas S.']",,,,
,PMC,Optimization of Human Immunodeficiency Virus Gag Expression by Newcastle Disease Virus Vectors for the Induction of Potent Immune Responses,http://dx.doi.org/10.1128/JVI.01443-08,PMC2612356,,,"One attractive strategy for the development of a human immunodeficiency virus (HIV) vaccine is the use of viral vectors with a proven safety profile and an absence of preexisting immunity in humans, such as Newcastle disease virus (NDV). Several NDV vaccine vectors have been generated, and their immunogenicities have been investigated with different animal models. However, a systematic study to evaluate the optimal insertion site of the foreign antigens into NDV that results in enhanced immune responses specific to the antigen has not yet been conducted. In this article, we describe the ability of NDV expressing HIV Gag to generate a Gag-specific immune response in mice. We also have determined the optimal insertion site into the NDV genome by generating recombinant NDV-HIVGag viruses in which HIV gag was located at different transcriptional positions throughout the NDV viral genome. All recombinant viruses were viable, grew to similar titers in embryonated chicken eggs, and expressed Gag in a stable manner. Our in vivo experiments revealed that higher HIV Gag protein expression positively correlates with an enhanced CD8(+) T-cell-mediated immune response and protective immunity against challenge with vaccinia virus expressing HIV Gag. We also inserted a codon-optimized version of HIV gag in the described best location, between the P and M genes. Virus expressing the codon-optimized version of HIV gag induced a higher expression of the protein and an enhanced immune response against HIV Gag in mice. These results indicate that strategies directed toward increasing antigen expression by NDV result in enhanced immunogenicity and vaccine efficacy.",,"['Carnero, Elena', 'Li, Wenjing', 'Borderia, Antonio V.', 'Moltedo, Bruno', 'Moran, Thomas', 'García-Sastre, Adolfo']",,,,
,PMC,"Genome and proteome annotation: organization, interpretation and integration",http://dx.doi.org/10.1098/rsif.2008.0341,PMC2658791,,,"Recent years have seen a huge increase in the generation of genomic and proteomic data. This has been due to improvements in current biological methodologies, the development of new experimental techniques and the use of computers as support tools. All these raw data are useless if they cannot be properly analysed, annotated, stored and displayed. Consequently, a vast number of resources have been created to present the data to the wider community. Annotation tools and databases provide the means to disseminate these data and to comprehend their biological importance. This review examines the various aspects of annotation: type, methodology and availability. Moreover, it puts a special interest on novel annotation fields, such as that of phenotypes, and highlights the recent efforts focused on the integrating annotations.",,"['Reeves, Gabrielle A.', 'Talavera, David', 'Thornton, Janet M.']",,,,
,PMC,Genetic Vaccines for Anthrax Based on Recombinant Adeno-associated Virus Vectors,http://dx.doi.org/10.1038/mt.2008.242,PMC2835057,,,"Bacillus anthracis represents a formidable bioterrorism and biowarfare threat for which new vaccines are needed with improved safety and efficacy over current options. Toward this end, we created recombinant adeno-associated virus type 1 (rAAV1) vectors containing synthetic genes derived from the protective antigen (PA) or lethal factor (LF) of anthrax lethal toxin (LeTx) and tested them for immunogenicity and induction of toxin-neutralizing antibodies in rabbits. Codon-optimized segments encoding activated PA (PA63), or LF, were synthesized and cloned into optimized rAAV1 vectors containing a human cytomegalovirus (hCMV) promoter and synthetic optimized leader. Serum from rabbits immunized intramuscularly with rAAV1/PA (monovalent), rAAV1/LF (monovalent), rAAV1/PA + rAAV1/LF (bivalent), or rAAV1/enhanced green fluorescent protein (control) exhibited substantial PA- and LF-specific antibody responses at 4 weeks by both western blot (> 1:10,000 dilution) and enzyme-linked immunosorbent assay (ELISA) (mean end-point titer: 32,000–260,000), and contained anthrax LeTx–neutralizing activity in vitro, with peak titers approximating those of a rabbit hyperimmune antisera raised against soluble PA and LF. Compared to the monovalent groups (rAAV1/PA or rAAV1/LF), the bivalent group (rAAV1/PA + rAAV1/LF) exhibited marginally higher ELISA and neutralization activity with dual specificity for both PA and LF. The finding of robust neutralizing antibody responses after a single injection of these rAAV1-based vectors supports their further development as candidate anthrax vaccines.",,"['Liu, Te-Hui', 'Oscherwitz, Jon', 'Schnepp, Bruce', 'Jacobs, Jana', 'Yu, Fen', 'Cease, Kemp B', 'Johnson, Philip R']",,,,
,PMC,Enhanced immune stimulation by a therapeutic lymphoma tumor antigen vaccine produced in insect cells involves mannose receptor targeting to antigen presenting cells,http://dx.doi.org/10.1016/j.vaccine.2008.10.055,PMC2683685,,,"Therapeutic vaccination of lymphoma patients with tumor-specific immunoglobulin (idiotype, Id) coupled to the carrier protein keyhole limpet hemocyanin (Id-KLH) is undergoing clinical investigation, and methods to improve the immunogenicity of these and other protein tumor antigen vaccines are being sought. Id proteins can be produced via tumor-myeloma hybridomas or recombinant methods in mammalian, bacteria, or insect cells. We now demonstrate that terminal mannose residues, characteristic of recombinant proteins produced in insect cells, yield Id proteins with significantly enhanced immunostimulatory properties compared to Id proteins derived from mammalian cells. Recombinant baculovirus-infected insect cell-derived Id showed higher binding to and activation of human dendritic cells mediated by mannose receptors. In vivo, insect cell-derived Id elicited higher levels of tumor-specific CD8(+) CTL and improved eradication of pre-established murine lymphoma. Insect cell and mammalian Id generated similar levels of tumor-specific antibodies, showing no impairment in antibody responses to native tumor antigen despite the glycoslylation differences in the immunogen. Combining insect cell production and maleimide-based KLH conjugation offered the highest levels of anti-tumor immunity. Our data comparing sources of recombinant Id protein tumor antigens used in therapeutic cancer vaccines demonstrate that insect cell-derived antigens can offer several immunologic advantages over proteins derived from mammalian sources.",,"['Betting, David J.', 'Mu, Xi Y.', 'Kafi, Kamran', 'McDonnel, Desmond', 'Rosas, Francisco', 'Gold, Daniel P.', 'Timmerman, John M.']",,,,
,PMC,Humoral and Cellular Immune Responses Induced by 3a DNA Vaccines against Severe Acute Respiratory Syndrome (SARS) or SARS-Like Coronavirus in Mice,http://dx.doi.org/10.1128/CVI.00261-08,PMC2620671,,,"Vaccine development for severe acute respiratory syndrome coronavirus (SARS-CoV) has mainly focused on the spike (S) protein. However, the variation of the S gene between viruses may affect the efficacy of a vaccine, particularly for cross-protection against SARS-like CoV (SL-CoV). Recently, a more conserved group-specific open reading frame (ORF), the 3a gene, was found in both SARS-CoV and SL-CoV. Here, we studied the immunogenicity of human SARS-CoV 3a and bat SL-CoV 3a DNA vaccines in mice through electroporation immunization followed by enzyme-linked immunosorbent, enzyme-linked immunospot, and flow cytometry assays. Our results showed that high levels of specific humoral responses were induced by SARS-CoV 3a and SL-CoV 3a DNA vaccines. Furthermore, a strong Th1-based cellular immune response was stimulated by both DNA vaccines. The vaccines stimulated gamma interferon production mainly by CD8(+) T cells and interleukin-2 (IL-2) mainly by CD4(+) T cells. Of interest, the frequency of IL-2-positive cells elicited by the SARS-CoV 3a DNA vaccine was significantly higher than that elicited by the SL-CoV 3a DNA vaccine. In summary, our study provides a reference for designing cross-protective DNA vaccines based on the group-specific ORFs of CoVs.",,"['Lu, Baojing', 'Tao, Ling', 'Wang, Ting', 'Zheng, Zhenhua', 'Li, Bao', 'Chen, Ze', 'Huang, Yi', 'Hu, Qinxue', 'Wang, Hanzhong']",,,,
,PMC,Simple Tests for Rapid Detection of Canine Parvovirus Antigen and Canine Parvovirus-Specific Antibodies,http://dx.doi.org/10.1128/CVI.00304-08,PMC2620666,,,"Canine parvovirus (CPV) is the number one viral cause of enteritis, morbidity, and mortality in 8-week-old young puppies. We have developed twin assays (slide agglutination test [SAT] for CPV antigen and slide inhibition test [SIT] for CPV antibody) that are sensitive, specific, cost-effective, generic for all genotypes of CPV, and provide instant results for CPV antigen detection in feces and antibody quantification in serum. We found these assays to be useful for routine applications in kennels with large numbers of puppies at risk. The results of these assays are available in 1 min and do not require any special instrumentation. SAT-SIT technology will find applications in rapid screening of samples for other hemagglutinating emerging viruses of animals and humans (influenza virus and severe acute respiratory syndrome coronavirus).",,"['Marulappa, Shashidhara Y.', 'Kapil, Sanjay']",,,,
,PMC,Angiotensin converting enzyme 2 in the brain: properties and future directions,http://dx.doi.org/10.1111/j.1471-4159.2008.05723.x,PMC2667944,,,"Angiotensin (Ang) converting enzyme (ACE) 2 cleaves Ang-II into the vasodilator peptide Ang-(1-7), thus acting as a pivotal element in balancing the local effects of these peptides. ACE2 has been identified in various tissues and is supposed to be a modulator of cardiovascular function. Decreases in ACE2 expression and activity have been reported in models of hypertension, heart failure, atherosclerosis, diabetic nephropathy and others. In addition, the expression level and/or activity are affected by other renin-angiotensin system components (e.g. ACE and AT1 receptors). Local inhibition or global deletion of brain ACE2 induces a reduction in baroreflex sensitivity. Moreover, ACE2-null mice have been shown to exhibit either blood pressure (BP) or cardiac dysfunction phenotypes. On the other hand, over-expression of ACE2 exerts protective effects in local tissues, including the brain. In this review, we will first summarize the major findings linking ACE2 to cardiovascular function in the periphery then focus on recent discoveries related to ACE2 in the central nervous system. Finally, we will unveil new tools designed to address the importance of central ACE2 in various diseases, and discuss the potential for this carboxypeptidase as a new target in the treatment of hypertension and other cardiovascular diseases.",,"['Xia, Huijing', 'Lazartigues, Eric']",,,,
,PMC,Identification of Major Histocompatibility Complex Class I C Molecule as an Attachment Factor That Facilitates Coronavirus HKU1 Spike-Mediated Infection,http://dx.doi.org/10.1128/JVI.01387-08,PMC2612401,,,"Human coronavirus HKU1 (HCoV-HKU1) is a recently discovered human coronavirus associated with respiratory tract infections worldwide. In this study, we have identified the major histocompatibility complex class I C molecule (HLA-C) as an attachment factor in facilitating HCoV-HKU1 spike (S)-mediated infection. HCoV-HKU1 S pseudotyped virus was assembled using a human immunodeficiency virus type 1-derived reporter virus harboring the human codon-optimized spike of HCoV-HKU1. We identified human alveolar epithelial A549 cells as the most susceptible cell line among those tested to infection by HCoV-HKU1 S pseudotypes. A549 cells were shown to bind purified soluble HCoV-HKU1 S(1-600) glycopeptide. To search for the functional receptor for HCoV-HKU1, an A549 cDNA expression library was constructed and transduced into the nonpermissive, baby hamster kidney cells line BHK-21. Transduced cells that bind soluble HCoV-HKU1 S(1-600) glycoprotein with C-terminal FLAG were sorted. Sequencing of two independent clones revealed cDNA inserts encoding HLA-C. Inhibition of HLA-C expression or function by RNAi silencing and anti-HLA-C antibody decreased HCoV-HKU1 S pseudotyped virus infection of A549 cells by 62 to 65%, whereas pretreatment of cells with neuraminidase decreased such infection by only 13%. When HLA-C was constitutively expressed in another nonpermissive cell line, NIH-3T3, quantitative PCR showed that the binding of HCoV-HKU1 S pseudotyped virus to cell surfaces was increased by 200-fold, but the cells remained nonsusceptible to HCoV-HKU1 S pseudotyped virus infection. Our data suggest that HLA-C is involved in the attachment of HCoV-HKU1 to A549 cells and is a potential candidate to facilitate cell entry. However, other unknown surface proteins on A549 cells may be concomitantly utilized by S glycoprotein of HCoV-HKU1 during viral entry. Further studies are required to elucidate other putative receptors or coreceptors for HCoV-HKU1 and the mechanism of HCoV-HKU1 S-mediated cell entry.",,"['Chan, Che Man', 'Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Tse, Herman', 'Zheng, Bo-Jian', 'Chen, Ling', 'Huang, Jian-Dong', 'Yuen, Kwok-Yung']",,,,
,PMC,Crystal Structures of Two Coronavirus ADP-Ribose-1″-Monophosphatases and Their Complexes with ADP-Ribose: a Systematic Structural Analysis of the Viral ADRP Domain,http://dx.doi.org/10.1128/JVI.01862-08,PMC2612350,,,"The coronaviruses are a large family of plus-strand RNA viruses that cause a wide variety of diseases both in humans and in other organisms. The coronaviruses are composed of three main lineages and have a complex organization of nonstructural proteins (nsp's). In the coronavirus, nsp3 resides a domain with the macroH2A-like fold and ADP-ribose-1""-monophosphatase (ADRP) activity, which is proposed to play a regulatory role in the replication process. However, the significance of this domain for the coronaviruses is still poorly understood due to the lack of structural information from different lineages. We have determined the crystal structures of two viral ADRP domains, from the group I human coronavirus 229E and the group III avian infectious bronchitis virus, as well as their respective complexes with ADP-ribose. The structures were individually solved to elucidate the structural similarities and differences of the ADRP domains among various coronavirus species. The active-site residues responsible for mediating ADRP activity were found to be highly conserved in terms of both sequence alignment and structural superposition, whereas the substrate binding pocket exhibited variations in structure but not in sequence. Together with data from a previous analysis of the ADRP domain from the group II severe acute respiratory syndrome coronavirus and from other related functional studies of ADRP domains, a systematic structural analysis of the coronavirus ADRP domains was realized for the first time to provide a structural basis for the function of this domain in the coronavirus replication process.",,"['Xu, Yuanyuan', 'Cong, Le', 'Chen, Cheng', 'Wei, Lei', 'Zhao, Qi', 'Xu, Xiaoling', 'Ma, Yanlin', 'Bartlam, Mark', 'Rao, Zihe']",,,,
,PMC,Positional-scanning fluorogenic substrate libraries reveal unexpected specificity determinants of deubiquitinating enzymes (DUBs),http://dx.doi.org/10.1042/BJ20080779,PMC2766241,,,"Deubiquitinating enzymes (DUBs) are a family of proteases responsible for the specific removal of ubiquitin attached to target proteins and thus control the free cellular pools of this molecule. DUB activity is usually assayed using full-length ubiquitin, and these enzymes generally show low activity on small substrates that constitute the P4-P1 LRGG C-terminal motif of ubiquitin. To gain insight into the C-terminal recognition region of ubiquitin by DUBs we synthesized positional scanning libraries of fluorogenic tetrapeptides and tested them on three examples of human DUBs (OTU-1, Iso-T and UCH-L3) and one viral ubiquitin specific protease – Plpro from West Nile virus. In most cases the results show flexibility in the P4 position, very high specificity for Arg in P3 position and Gly at P2 – in accord with the sequence of the natural substrate ubiquitin. Surprisingly, screening of the P2 position revealed that UCH-L3 in contrast to all the other tested DUBs, demonstrates substantial tolerance of Ala and Val at P2, and a parallel analysis using the appropriate mutation of the full-length ubiquitin confirms this. We have also used an optimal tetrapeptide substrate, Ac-LRGG-AFC to investigate the activation mechanism of DUBs by ubiquitin and elevated salts concentration. Together, our results reveal the importance of the dual features of 1) substrate specificity and 2) the mechanism of ubiquitin binding in determining deubiquitination by this group of proteases.",,"['Drag, Marcin', 'Mikolajczyk, Jowita', 'Bekes, Miklos', 'Reyes-Turcu, Francisca E.', 'Ellman, Jonathan A.', 'Wilkinson, Keith D.', 'Salvesen, Guy S.']",,,,
,PMC,Adoptive Immunotherapy against Allogeneic Kidney Grafts in Dogs with Stable Hematopoietic Trichimerism,http://dx.doi.org/10.1016/j.bbmt.2008.08.005,PMC2603466,,,"Dogs given nonmyeloablative conditioning and marrow grafts from two dog leukocyte antigen- (DLA) identical littermate donors developed stable trichimerism and stably accepted a subsequent kidney graft from one of the marrow donors without the need for immunosuppression. Here, we used trichimeras to evaluate strategies of adoptive immunotherapy to solid tumors, using the kidney as a tumor surrogate. Three DLA-identical trichimeric recipients were established by simultaneously infusing marrow from two DLA-identical donor dogs into a DLA-identical recipient conditioned with 2 Gy total body irradiation and given a short course of postgrafting immunosuppression. After confirming stable hematopoietic engraftment, a kidney was transplanted from one of the two marrow donors into each respective trichimeric recipient. Peripheral blood lymphocytes (PBL) from each kidney donor were then used to sensitize the alternate marrow donor. Donor lymphocyte infusions (DLI) from the sensitized dogs were given to the trichimeric recipients, whereupon chimerism, graft-versus-host disease (GvHD), and kidney rejection were monitored. After DLI, we observed both prompt rejection of the transplanted marrow-donor kidney and disappearance of corresponding hematopoietic chimerism. Presumably, owing to shared minor histocompatibility antigens, host chimerism also disappeared and GvHD in skin, gut, and liver developed. The native kidneys, while showing lymphocytic infiltration, remained functionally normal. The current study demonstrated that under certain experimental conditions, the kidney, an organ ordinarily not involved in graft-versus-host reactions, can be targeted by sensitized donor lymphocytes.",,"['Graves, Scott S.', 'Hogan, William J.', 'Kuhr, Christian', 'Diaconescu, Razvan', 'Harkey, Michael', 'Sale, George E.', 'Stone, Brad', 'Georges, George E.', 'Storb, Rainer']",,,,
,PMC,Making health care affordable in China,http://dx.doi.org/10.2471/BLT.08.011108,PMC2649548,,,"China is taking steps towards its goal of providing every single person in the country with access to modern health-care services, in part through health financing schemes. Jane Parry and Cui Weiyuan report.",,,,,,
,PMC,Applying the Lessons of SARS to Pandemic Influenza: An Evidence-based Approach to Mitigating the Stress Experienced by Healthcare Workers,http://dx.doi.org/10.1007/BF03403782,PMC5148615,,,"We describe an evidence-based approach to enhancing the resilience of healthcare workers in preparation for an influenza pandemic, based on evidence about the stress associated with working in healthcare during the SARS outbreak. SARS was associated with significant long-term stress in healthcare workers, but not with increased mental illness. Reducing pandemic-related stress may best be accomplished through interventions designed to enhance resilience in psychologically healthy people. Applicable models to improve adaptation in individuals include Folkman and Greer’s framework for stress appraisal and coping along with psychological first aid. Resilience is supported at an organizational level by effective training and support, development of material and relational reserves, effective leadership, the effects of the characteristics of “magnet hospitals,” and a culture of organizational justice. Evidence supports the goal of developing and maintaining an organizational culture of resilience in order to reduce the expected stress of an influenza pandemic on healthcare workers. This recommendation goes well beyond the provision of adequate training and counseling. Although the severity of a pandemic is unpredictable, this effort is not likely to be wasted because it will also support the health of both patients and staff in normal times.",,"['Maunder, Robert G.', 'Leszcz, Molyn', 'Savage, Diane', 'Adam, Mary Anne', 'Peladeau, Nathalie', 'Romano, Donna', 'Rose, Marci', 'Schulman, Rabbi Bernard']",,,,
,PMC,Therapeutically targeting RNA viruses via lethal mutagenesis,http://dx.doi.org/10.2217/17460794.3.6.553,PMC2630198,,,"RNA viruses exhibit increased mutation frequencies relative to other organisms. Recent work has attempted to exploit this unique feature by increasing the viral mutation frequency beyond an extinction threshold, an antiviral strategy known as lethal mutagenesis. A number of novel nucleoside analogs have been designed around this premise. Herein, we review the quasispecies nature of RNA viruses and survey the antiviral, biological and biochemical characteristics of mutagenic nucleoside analogs, including clinically-used ribavirin. Biological implications of modulating viral replication fidelity are discussed in the context of translating lethal mutagenesis into a clinically-useful antiviral strategy.",,"['Graci, Jason D', 'Cameron, Craig E']",,,,
,PMC,"The Use of Cross-foster Rederivation to Eliminate Murine Norovirus, Helicobacter spp., and Murine Hepatitis Virus from a Mouse Colony",,PMC2687133,,,"Over 10 mo, 287 mouse litters were cross-fostered by using 1 of 2 paradigms to eliminate murine norovirus (MNV), Helicobacter spp., murine hepatitis virus (MHV), and Syphacia obvelata. Paradigm 1 involved cross-fostering litters at younger than 48 h with no attention to the changing of bedding material. Paradigm 2 involved cross-fostering litters at younger than 24 h from cages in which the bedding material was changed within 24 h before cross-fostering. After cross-foster rederivation, mice were tested for the presence of Helicobacter spp. by means of fecal PCR at 4, 8, and 12 wk. Surrogates also were tested for MNV by use of multiplex fluorometric assay serology at 4 wk and fecal PCR at 12 wk. Surrogate mice were tested for MHV by means of MFIA at 4 wk and for pinworms by perianal tape test and fecal flotation at 4 and 12 wk. Compared with those from paradigm 1, litters from paradigm 2 were less likely to be positive for MHV and Helicobacterspp. The use of cross-foster rederivation alone was unsuccessful for the elimination of Syphacia obvelata. For cross-foster rederivation, we recommend that litters be younger than 24 h and from cages in which the bedding material was changed within 24 h before cross-fostering. The presence of MNV, Helicobacter spp., and MHV can be predicted reliably at 12, 8, and 4 wk, respectively.",,"['Artwohl, James E', 'Purcell, Jeanette E', 'Fortman, Jeffrey D']",,,,
,PMC,Emerging infections: a perpetual challenge,http://dx.doi.org/10.1016/S1473-3099(08)70256-1,PMC2599922,,,"Emerging and re-emerging infectious diseases, and their determinants, have recently attracted substantial scientific and popular attention. HIV/AIDS, severe acute respiratory syndrome, H5N1 avian influenza, and many other emerging diseases have either proved fatal or caused international alarm. Common and interactive co-determinants of disease emergence, including population growth, travel, and environmental disruption, have been increasingly documented and studied. Are emerging infections a new phenomenon related to modern life, or do more basic determinants, transcending time, place, and human progress, govern disease generation? By examining a number of historically notable epidemics, we suggest that emerging diseases, similar in their novelty, impact, and elicitation of control responses, have occurred throughout recorded history. Fundamental determinants, typically acting in concert, seem to underlie their emergence, and infections such as these are likely to continue to remain challenges to human survival.",,"['Morens, David M', 'Folkers, Gregory K', 'Fauci, Anthony S']",,,,
,PMC,Activation of TORC1 Transcriptional Coactivator through MEKK1-induced Phosphorylation,http://dx.doi.org/10.1091/mbc.E08-04-0369,PMC2575155,,,"CREB is a prototypic bZIP transcription factor and a master regulator of glucose metabolism, synaptic plasticity, cell growth, apoptosis, and tumorigenesis. Transducers of regulated CREB activity (TORCs) are essential transcriptional coactivators of CREB and an important point of regulation on which various signals converge. In this study, we report on the activation of TORC1 through MEKK1-mediated phosphorylation. MEKK1 potently activated TORC1, and this activation was independent of downstream effectors MEK1/MEK2, ERK2, JNK, p38, protein kinase A, and calcineurin. MEKK1 induced phosphorylation of TORC1 both in vivo and in vitro. Expression of the catalytic domain of MEKK1 alone in cultured mammalian cells sufficiently caused phosphorylation and subsequent activation of TORC1. MEKK1 physically interacted with TORC1 and stimulated its nuclear translocation. An activation domain responsive to MEKK1 stimulation was mapped to amino acids 431–650 of TORC1. As a physiological activator of CREB, interleukin 1α triggered MEKK1-dependent phosphorylation of TORC1 and its consequent recruitment to the cAMP response elements in the interleukin 8 promoter. Taken together, our findings suggest a new mechanism for regulated activation of TORC1 transcriptional coactivator and CREB signaling.",,"['Siu, Yeung-Tung', 'Ching, Yick-Pang', 'Jin, Dong-Yan']",,,,
,PMC,CEACAM1 and the regulation of mucosal inflammation,http://dx.doi.org/10.1038/mi.2008.50,PMC3901578,,,"Inflammatory bowel disease (IBD) is characterized by unrestrained T-cell activation that results in the production of a variety of inflammatory cytokines and other mediators. Understanding the mechanisms of T-cell regulation is therefore of significant importance to IBD and other forms of dysregulated-mucosal inflammation. An area that is of significant interest are the cell autonomous mechanisms of T-cell regulation through proteins that have natural inhibitory functions when expressed on T lymphocytes. One such molecule is carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1). CEACAM1 is primarily an activation-induced cell-surface molecule that functions as a co-inhibitory receptor. Homophilic ligation of CEACAM1 on T cells leads to a signaling mechanism, which results in inhibition of a broad range T-cell functions. CEACAM1 therefore represents a new potential therapeutic target in the treatment of IBD.",,"['Nagaishi, T', 'Chen, Z', 'Chen, L', 'Iijima, H', 'Nakajima, A', 'Blumberg, RS']",,,,
,PMC,The prevalence of preterm birth and season of conception,http://dx.doi.org/10.1111/j.1365-3016.2008.00971.x,PMC4288966,,,"Preterm birth is a major obstetric problem. An exploration of the season of conception in relation to preterm birth may provide direction in the search for risk factors. We conducted a retrospective cohort study of 82 213 singleton livebirths (20–45 weeks’ gestation) to 61 630 women at Magee-Womens Hospital, Pittsburgh, PA, from 1995 to 2005. Conception was estimated based on gestational age determined by best obstetric estimate. Fourier series analysis was used to model seasonal trends. Spontaneous preterm birth at <37 weeks was associated with conception season (P < 0.05). The peak prevalence occurred among conceptions in winter and spring (peaking February 23 at 6.9%), with an average trough among late summer/early autumn conceptions (August 25 at 6.2%). The pattern for spontaneous preterm birth <32 weeks was similar (P < 0.05), with the peak on March 13 (1.7%), and nadir on September 12 (1.4%). Results were similar when indicated preterm births were included. These seasonal changes may increase our insight into the role of exposures with seasonal periodicity in the pathophysiology of preterm birth.",,"['Bodnar, Lisa M.', 'Simhan, Hyagriv N.']",,,,
,PMC,RNAVLab: A virtual laboratory for studying RNA secondary structures based on grid computing technology,,PMC2714649,,,"As ribonucleic acid (RNA) molecules play important roles in many biological processes including gene expression and regulation, their secondary structures have been the focus of many recent studies. Despite the computing power of supercomputers, computationally predicting secondary structures with thermodynamic methods is still not feasible when the RNA molecules have long nucleotide sequences and include complex motifs such as pseudoknots. This paper presents RNAVLab (RNA Virtual Laboratory), a virtual laboratory for studying RNA secondary structures including pseudoknots that allows scientists to address this challenge. Two important case studies show the versatility and functionalities of RNAVLab. The first study quantifies its capability to rebuild longer secondary structures from motifs found in systematically sampled nucleotide segments. The extensive sampling and predictions are made feasible in a short turnaround time because of the grid technology used. The second study shows how RNAVLab allows scientists to study the viral RNA genome replication mechanisms used by members of the virus family Nodaviridae.",,"['Taufer, Michela', 'Leung, Ming-Ying', 'Solorio, Thamar', 'Licon, Abel', 'Mireles, David', 'Araiza, Roberto', 'Johnson, Kyle L.']",,,,
,PMC,Structural Features and the Persistence of Acquired Proteins,http://dx.doi.org/10.1002/pmic.200800061,PMC3014317,,,"ORFan genes can constitute a large fraction of a bacterial genome, but due to their lack of homologs, their functions have remained largely unexplored. To determine if particular features of ORFan-encoded proteins promote their presence in a genome, we analyzed properties of ORFans that originated over a broad evolutionary timescale. We also compared ORFan genes to another class of acquired genes (HOPs), which have homologs in other bacteria. A total of 54 ORFan and HOP genes selected from different phylogenetic depths in the Escherichia coli lineage were cloned, expressed, purified and subjected to CD spectroscopy. A majority of genes could be expressed, but only 18 yielded sufficient soluble protein for spectral analysis. Of these, half were significantly α-helical, three were predominantly β-sheet, and six were of intermediate or indeterminate structure. Although a higher proportion of HOPs yielded soluble proteins with resolvable secondary structures, ORFans resembled HOPs with regard to most of the other features tested. Overall, we found that those ORFan and HOP genes that have persisted in the E. coli lineage were more likely to encode soluble and folded proteins, more likely to display environmental modulation of their gene expression, and by extrapolation, are more likely to be functional.",,"['Narra, Hema Prasad', 'Cordes, Matthew H. J.', 'Ochman, Howard']",,,,
,PMC,Characterization of the termination–reinitiation strategy employed in the expression of influenza B virus BM2 protein,http://dx.doi.org/10.1261/rna.1231008,PMC2578862,,,"Coupled expression of the M1 and BM2 open-reading frames (ORFs) of influenza B from the dicistronic segment 7 mRNA occurs by a process of termination-dependent reinitiation. The AUG start codon of the BM2 ORF overlaps the stop codon of the upstream M1 ORF in the pentanucleotide UAAUG, and BM2 synthesis is dependent upon translation of the M1 ORF and termination at the stop codon. Here, we have investigated the mRNA sequence requirements for BM2 expression. Termination–reinitiation is dependent upon 45 nucleotide (nt) of RNA immediately upstream of the UAAUG pentanucleotide, which includes an essential stretch complementary to 18S rRNA helix 26. Thus, similar to the caliciviruses, base-pairing between mRNA and rRNA is likely to play a role in tethering the 40S subunit to the mRNA following termination at the M1 stop codon. Consistent with this, repositioning of the M1 stop codon more than 24 nt downstream from the BM2 start codon inhibited BM2 expression. RNA structure probing revealed that the RNA upstream of the UAAUG overlap is not highly structured, but upon encountering the M1 stop codon by the ribosome, a stem–loop may form immediately 5′ of the ribosome, with the 18S rRNA complementary region in the apical loop and in close proximity to helix 26. Mutational analysis reveals that the normal requirements for start site selection in BM2 expression are suspended, with little effect of initiation codon context and efficient use of noncanonical initiation codons. This suggests that the full complement of initiation factors is not required for the reinitiation process.",,"['Powell, Michael L.', 'Napthine, Sawsan', 'Jackson, Richard J.', 'Brierley, Ian', 'Brown, T. David K.']",,,,
,PMC,Viruses & kidney disease: beyond HIV,http://dx.doi.org/10.1016/j.semnephrol.2008.08.010,PMC2629127,,,"HIV-infected patients may acquire new viral co-infections; they may also experience the reactivation or worsening of existing viral infections, including active, smoldering, or latent infections. HIV-infected patients may be predisposed to these viral infections due to immunodeficiency or to risk factors common to HIV and other viruses. A number of these affect the kidney, either by direct infection or by deposition of immune complexes. In this review we discuss the renal manifestations and treatment of hepatitis C virus, BK virus, adenovirus, cytomegalovirus, and parvovirus B19 in patients with HIV disease. We also discuss an approach to the identification of new viral renal pathogens, using a viral gene chip to identify viral DNA or RNA.",,"['Waldman, Meryl', 'Marshall, Vickie', 'Whitby, Denise', 'Kopp, Jeffrey B.']",,,,
,PMC,The piglet as a model for B cell and immune system development,http://dx.doi.org/10.1016/j.vetimm.2008.10.321,PMC2828348,,,"The ability to identify factors responsible for disease in all species depends on the ability to separate those factors which are environmental from those that are intrinsic. This is particularly important for studies on the development of the adaptive immune response of neonates. Studies on laboratory rodents or primates have been ambiguous because neither the effect of environmental nor maternal factors on the newborn can be controlled in mammals that: (i) transmit potential maternal immunoregulatory factors in utero and (ii) are altricial and cannot be reared after birth without their mothers. Employing the newborn piglet model can address each of these concerns. However, it comes at the price of having first to characterize the immune system of swine and its development. This review focuses on the porcine B cell system, especially on the methods used for its characterization in fetal studies and neonatal piglets. Understanding these procedures is important in the interpretation of the data obtained. Studies on neonatal piglets have (a) provided valuable information on the development of the adaptive immune system, (b) lead to important advances in evolutionary biology, (c) aided our understanding of passive immunity and (d) provided opportunities to use swine to address specific issues in veterinary and biomedical research and immunotherapy. This review summarizes the history of the development of the piglet as a model for antibody repertoire development, thus providing a framework to guide future investigators.",,"['Butler, J.E.', 'Lager, K.M.', 'Splichal, I.', 'Francis, D.', 'Kacskovics, I.', 'Sinkora, M.', 'Wertz, N.', 'Sun, J.', 'Zhao, Y.', 'Brown, W.R.', 'DeWald, R.', 'Dierks, S.', 'Muyldermans, S.', 'Lunney, J.K.', 'McCray, P.B.', 'Rogers, C.S.', 'Welsh, M.J.', 'Navarro, P.', 'Klobasa, F.', 'Habe, F.', 'Ramsoondar, J.']",,,,
,PMC,Rationally Designed Anti-HIV Peptides Containing Multifunctional Domains as Molecule Probes for Studying the Mechanisms of Action of the First and Second Generation HIV Fusion Inhibitors,http://dx.doi.org/10.1074/jbc.M804672200,PMC2573079,,,"We have previously shown that the first generation human immunodeficiency virus (HIV) fusion inhibitor T20 (Fuzeon) contains a critical lipid-binding domain (LBD), whereas C34, another anti-HIV peptide derived from the gp41 C-terminal heptad repeat, consists of an important pocket-binding domain (PBD), and both share a common 4-3 heptad repeat (HR) sequence (Liu, S., Jing, W., Cheung, B., Lu, H., Sun, J., Yan, X., Niu, J., Farmar, J., Wu, S., and Jiang, S. (2007) J. Biol. Chem. 282,9612 -962017276993). T1249, the second generation HIV fusion inhibitor, has both LBD and PBD but a different HR sequence, suggesting that these three anti-HIV peptides may have distinct mechanisms of action. Here we rationally designed a set of peptides that contain multiple copies of a predicted HR sequence (5HR) or the HR sequence plus either LBD (4HR-LBD) or PBD (PBD-4HR) or both (PBD-3HR-LBD), and we compared their anti-HIV-1 activity and biophysical properties. We found that the peptide 5HR exhibited low-to-moderate inhibitory activity on HIV-1-mediated cell-cell fusion, whereas addition of LBD and/or PBD to the HR sequence resulted in a significant increase of the anti-HIV-1 activity. The peptides containing PBD, including PBD-4HR and PBD-3HR-LBD, could form a stable six-helix bundle with the N-peptide N46 and effectively blocked the gp41 core formation, whereas the peptides containing LBD, e.g. 4HR-LBD and PBD-3HR-LBD, could interact with the lipid vehicles. These results suggest that the HR sequence in these anti-HIV peptides acts as a structure domain and is responsible for its interaction with the HR sequence in N-terminal heptad repeat, whereas PBD and LBD are critical for interactions with their corresponding targets. T20, C34, and T1249 may function like 4HR-LBD, PBD-4HR, and PBD-3HR-LBD, respectively, to interact with different target sites for inhibiting HIV fusion and entry. Therefore, this study provides important information for understanding the mechanisms of action of the peptic HIV-1 fusion inhibitors and for rational design of novel antiviral peptides against HIV and other viruses with class I fusion proteins.",,"['Qi, Zhi', 'Shi, Weiguo', 'Xue, Na', 'Pan, Chungen', 'Jing, Weiguo', 'Liu, Keliang', 'Jiang, Shibo']",,,,
,PMC,Toll-like receptor and innate cytokine responses induced by lactobacilli colonization and human rotavirus infection in gnotobiotic pigs,http://dx.doi.org/10.1016/j.vetimm.2008.10.322,PMC2653198,,,"Toll-like receptors (TLR) play an important role in the recognition of microbes by host sentinel cells that leads to the subsequent innate and adaptive immune responses. In this study, we evaluated the patterns of TLR2-, TLR3- and TLR9-expressing antigen presenting cells (APCs) in spleen and blood of gnotobiotic (Gn) pigs after colonization with a mixture of two strains of lactic acid bacteria (LAB), Lactobacillus acidophilus and Lactobacillus reuteri or infection with the virulent human rotavirus (HRV) Wa strain. We also assessed the influence of LAB on TLR and serum innate cytokine responses induced by HRV. Distributions of subpopulations of APCs [CD14+/−SWC3+CD11R1− monocytes/macrophages and CD14+/−SWC3+CD11R1+ conventional dendritic cells (cDCs)] were described in our previous report (Zhang, W., Wen, K., Azevedo, M.S., Gonzalez, A.M., Saif, L.J., Li, G., Yousef, A.E., Yuan, L., 2008. Lactic acid bacterial colonization and human rotavirus infection influence distribution and frequencies of monocytes/macrophages and dendritic cells in neonatal gnotobiotic pigs. Vet. Immunol. Immunopathol. 121, pp. 222–231). We demonstrated that LAB induced strong TLR2-expressing APC responses in blood and spleen, HRV induced a TLR3 response in spleen, and TLR9 responses were induced by either HRV (in spleen) or LAB (in blood). LAB and HRV have an additive effect on TLR2- and TLR9-expressing APC responses, consistent with the adjuvant effect of LAB. Overall, the frequencies of TLR-expressing CD14+ APCs were higher than CD14− APCs. LAB enhanced the IFN-γ and IL-4 responses in serum, but it had a suppressive effect on the TLR3- and TLR9-expressing CD14− APC responses in spleen and the serum IFN-α response induced by HRV. These results elucidated the systemic TLR2-, TLR3-, and TLR9-expressing monocyte/macrophage and cDC responses after HRV infection, LAB colonization, and the two combined. Our findings facilitate the understanding of the mechanism of LAB’s adjuvant effect on rotavirus vaccines and the diverse innate and adaptive immune responses induced by commensal LAB colonization versus rotavirus infection and the interactions between them.",,"['Wen, Ke', 'Azevedo, Marli S.P.', 'Gonzalez, Ana', 'Zhang, Wei', 'Saif, Linda J.', 'Li, Guohua', 'Yousef, Ahmed', 'Yuan, Lijuan']",,,,
,PMC,"Roles for the Recycling Endosome, Rab8, and Rab11 in hantavirus release from epithelial cells",http://dx.doi.org/10.1016/j.virol.2008.09.021,PMC2648827,,,"Hantavirus structural proteins are believed to localize to intracellular membranes often identified as Golgi membranes, in virus-infected cells. After virus budding into the Golgi luminal space, virus-containing vesicles are transported to the plasma membrane via trafficking pathways that are not well defined. Using the New World hantavirus, Andes virus, we have investigated the role of various Rab proteins in the release of hantavirus particles from infected cells. Rabs 8 and 11 were found to colocalize with Andes virus proteins in virus infected cells and when expressed from cDNA, implicating the recycling endosome as an organelle important for hantavirus infection. Small interfering RNA-mediated downregulation of Rab11a alone or Rab11a and Rab11b together resulted in a decrease in infectious virus particle secretion from infected cells. Downregulation of Rab8a did not alter infectious virus release but reduction of both isoforms did. These data implicate the recycling endosome and the Rab proteins associated with vesicular transport to or from this intracellular organelle as an important pathway for hantavirus trafficking to the plasma membrane.",,"['Rowe, Regina K.', 'Suszko, Jason W.', 'Pekosz, Andrew']",,,,
,PMC,Seroprevalence of Turkey Coronavirus in North American Turkeys Determined by a Newly Developed Enzyme-Linked Immunosorbent Assay Based on Recombinant Antigen,http://dx.doi.org/10.1128/CVI.00319-08,PMC2593163,,,"Turkey coronavirus (TCoV) causes diarrhea in young turkey poults, but little is known about its prevalence in the field. To address this, the complete nucleocapsid gene was cloned and expressed in Escherichia coli. Expressed nucleocapsid gene produced two distinct proteins (52 and 43 kDa); their specificity was confirmed by Western blotting using two different monoclonal antibodies. Recombinant N protein was purified and used as an antigen to develop an enzyme-linked immunosorbent assay (ELISA) for the serological detection of TCoV that was then validated using experimentally derived turkey serum. The N-based ELISA showed (97%) sensitivity and (93%) specificity for TCoV, which was significantly higher than an infectious bronchitis coronavirus-based commercial test for TCoV. To assess the utility of this recombinant ELISA, 360 serum samples from turkey farms in Ontario, Canada, and 81 serum samples from farms in Arkansas were tested for TCoV-specific antibodies. A high seroprevalence of TCoV was found in turkeys from the Ontario farms with 73.9% of breeders and 60.0% of meat turkeys testing seropositive using the N-based ELISA. Similarly, a high field prevalence was found in the turkeys from Arkansas, for which 64.2% of the serum samples tested seropositive.",,"['Gomaa, Maged H.', 'Yoo, Dongwan', 'Ojkic, Davor', 'Barta, John R.']",,,,
,PMC,Uncultivated Bacteria as Etiologic Agents of Intra-Amniotic Inflammation Leading to Preterm Birth,http://dx.doi.org/10.1128/JCM.01206-08,PMC2620857,,,"Intra-amniotic infection and inflammation are major causes of preterm birth (PTB). However, intra-amniotic inflammation is often detected in the absence of infection. This may partly be due to the culturing methods employed in hospital laboratories, which are unable to detect the uncultivated species. In this study, intra-amniotic microbial infections associated with PTB were examined by both culture and 16S rRNA-based culture-independent methods and were corroborated by the presence of intra-amniotic inflammation. Amniotic fluid (AF) specimens from 46 pregnancies complicated by PTB and 16 asymptomatic women were analyzed. No bacterial DNA was amplified in AF collected from the asymptomatic women. Among the 46 samples associated with PTB, bacterial DNA was amplified from all (16/16) of the culture-positive samples and 17% (5/30) of the culture-negative samples. In the culture-positive group, additional species were detected in more than half (9/16) of the cases by PCR and clone analysis. Altogether, approximately two- thirds of the species detected by the culture-independent methods were not isolated by culture. They included both uncultivated and difficult-to-cultivate species, such as Fusobacterium nucleatum, Leptotrichia (Sneathia) spp., a Bergeyella sp., a Peptostreptococcus sp., Bacteroides spp., and a species of the order Clostridiales. To examine intra-amniotic inflammation, an AF proteomic fingerprint (mass-restricted score) was determined by surface-enhanced laser desorption ionization-time-of-flight mass spectrometry. Inflammation was detected in all five samples which were culture negative but PCR positive. Women who were PCR positive more often had elevated interleukin-6 levels in their AF, histological chorioamnionitis, and funisitis and delivered neonates with early-onset neonatal sepsis. Previously unrecognized, uncultivated, or difficult-to-cultivate species may play a key role in the initiation of PTB.",,"['Han, Yiping W.', 'Shen, Tao', 'Chung, Peter', 'Buhimschi, Irina A.', 'Buhimschi, Catalin S.']",,,,
,PMC,Protease-Mediated Entry via the Endosome of Human Coronavirus 229E,http://dx.doi.org/10.1128/JVI.01933-08,PMC2612384,,,"Human coronavirus 229E, classified as a group I coronavirus, utilizes human aminopeptidase N (APN) as a receptor; however, its entry mechanism has not yet been fully elucidated. We found that HeLa cells infected with 229E via APN formed syncytia when treated with trypsin or other proteases but not in a low-pH environment, a finding consistent with syncytium formation by severe acute respiratory syndrome coronavirus (SARS-CoV). In addition, trypsin induced cleavage of the 229E S protein. By using infectious viruses and pseudotyped viruses bearing the 229E S protein, we found that its infection was profoundly blocked by lysosomotropic agents as well as by protease inhibitors that also prevented infection with SARS-CoV but not that caused by murine coronavirus mouse hepatitis virus strain JHMV, which enters cells directly from the cell surface. We found that cathepsin L (CPL) inhibitors blocked 229E infection the most remarkably among a variety of protease inhibitors tested. Furthermore, 229E infection was inhibited in CPL knockdown cells by small interfering RNA, compared with what was seen for a normal counterpart producing CPL. However, its inhibition was not so remarkable as that found with SARS-CoV infection, which seems to indicate that while CPL is involved in the fusogenic activation of 229E S protein in endosomal infection, not-yet-identified proteases could also play a part in that activity. We also found 229E virion S protein to be cleaved by CPL. Furthermore, as with SARS-CoV, 229E entered cells directly from the cell surface when cell-attached viruses were treated with trypsin. These findings suggest that 229E takes an endosomal pathway for cell entry and that proteases like CPL are involved in this mode of entry.",,"['Kawase, Miyuki', 'Shirato, Kazuya', 'Matsuyama, Shutoku', 'Taguchi, Fumihiro']",,,,
,PMC,Comparative Analysis of Complete Genome Sequences of Three Avian Coronaviruses Reveals a Novel Group 3c Coronavirus,http://dx.doi.org/10.1128/JVI.01977-08,PMC2612373,,,"In this territory-wide molecular epidemiology study of coronaviruses (CoVs) in Hong Kong involving 1,541 dead wild birds, three novel CoVs were identified in three different bird families (bulbul CoV HKU11 [BuCoV HKU11], thrush CoV HKU12 [ThCoV HKU12], and munia CoV HKU13 [MuCoV HKU13]). Four complete genomes of the three novel CoVs were sequenced. Their genomes (26,396 to 26,552 bases) represent the smallest known CoV genomes. In phylogenetic trees constructed using chymotrypsin-like protease (3CL(pro)), RNA-dependent RNA polymerase (Pol), helicase, spike, and nucleocapsid proteins, BuCoV HKU11, ThCoV HKU12, and MuCoV HKU13 formed a cluster distantly related to infectious bronchitis virus and turkey CoV (group 3a CoVs). For helicase, spike, and nucleocapsid, they were also clustered with a CoV recently discovered in Asian leopard cats, for which the complete genome sequence was not available. The 3CL(pro), Pol, helicase, and nucleocapsid of the three CoVs possessed higher amino acid identities to those of group 3a CoVs than to those of group 1 and group 2 CoVs. Unique genomic features distinguishing them from other group 3 CoVs include a distinct transcription regulatory sequence and coding potential for small open reading frames. Based on these results, we propose a novel CoV subgroup, group 3c, to describe this distinct subgroup of CoVs under the group 3 CoVs. Avian CoVs are genetically more diverse than previously thought and may be closely related to some newly identified mammalian CoVs. Further studies would be important to delineate whether the Asian leopard cat CoV was a result of interspecies jumping from birds, a situation analogous to that of bat and civet severe acute respiratory syndrome CoVs.",,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Lam, Carol S. F.', 'Lai, Kenneth K. Y.', 'Huang, Yi', 'Lee, Paul', 'Luk, Geraldine S. M.', 'Dyrting, Kitman C.', 'Chan, Kwok-Hung', 'Yuen, Kwok-Yung']",,,,
,PMC,Insertion of the CXC chemokine ligand 9 (CXCL9) into the mouse hepatitis virus genome results in protection from viral-induced encephalitis and hepatitis,http://dx.doi.org/10.1016/j.virol.2008.09.032,PMC2643215,,,"The role of the CXC chemokine ligand 9 (CXCL9) in host defense following infection with mouse hepatitis virus (MHV) was determined. Inoculation of the central nervous system (CNS) of CXCL9−/− mice with MHV resulted in accelerated and increased mortality compared to wildtype mice supporting an important role for CXCL9 in antiviral defense. In addition, infection of RAG1−/− or CXCL9−/− mice with a recombinant MHV expressing CXCL9 (MHV-CXCL9) resulted in protection from disease that correlated with reduced viral titers within the brain and NK cell-mediated protection in the liver. Survival in MHV-CXCL9-infected CXCL9−/− mice was associated with reduced viral burden within the brain that coincided with increased T cell infiltration. Similarly, viral clearance from the livers of MHV-CXCL9-infected mice was accelerated but independent of increased T cell or NK cell infiltration. These observations indicate that CXCL9 promotes protection from coronavirus-induced neurological and liver disease.",,"['Muse, Michael', 'Kane, Joy A. C.', 'Carr, Daniel J. J.', 'Farber, Joshua M.', 'Lane, Thomas E.']",,,,
,PMC,PREFERENTIAL USE OF THE VH5-51 GENE SEGMENT BY THE HUMAN IMMUNE RESPONSE TO CODE FOR ANTIBODIES AGAINST THE V3 DOMAIN OF HIV-1,http://dx.doi.org/10.1016/j.molimm.2008.09.005,PMC2693011,,,"Human anti-V3 monoclonal antibodies (mAbs) generated from HIV-1 infected individuals display diversity in the range of their cross-neutralization that may be related to their immunogenetic background. The study of the immunoglobulin (Ig) variable region gene usage of heavy chains have shown a preferential usage of the VH5-51 gene segment which was detected in 35% of 51 human anti-V3 mAbs. In contrast, human mAbs against other envelope regions of HIV-1 (anti-Env), including the CD4-binding domain, the CD4-induced epitope, and gp41 preferentially used the VH1-69 gene segment, and none of them used the VH5-51 gene. Furthermore, the usage of the VH4 family by anti-V3 mAbs was restricted to only one gene segment, VH4-59, while the VH3 gene family was used at a significantly lower frequency by all of the analyzed anti-HIV-1 mAbs. Multivariate analysis showed that usage of VH gene segments was significantly different between anti-V3 and anti-Env mAbs, and compared to antibodies from healthy subjects. In addition, the anti-V3 mAbs preferentially used the JH3 and D2-15 gene segments. The preferential usage of selected Ig gene segments and the characteristic pattern of Ig gene usage by anti-V3 mAbs can be related to the conserved structure of the V3 region.",,"['Gorny, Miroslaw K.', 'Wang, Xiao-Hong', 'Williams, Constance', 'Volsky, Barbara', 'Revesz, Kathy', 'Witover, Bradley', 'Burda, Sherri', 'Urbanski, Mateusz', 'Nyambi, Phillipe', 'Krachmarov, Chavdar', 'Pinter, Abraham', 'Zolla-Pazner, Susan', 'Nadas, Arthur']",,,,
,PMC,Development of a Nucleocapsid-Based Human Coronavirus Immunoassay and Estimates of Individuals Exposed to Coronavirus in a U.S. Metropolitan Population,http://dx.doi.org/10.1128/CVI.00124-08,PMC2593164,,,"Coronaviruses cause respiratory infections ranging from common colds to severe acute respiratory syndrome (SARS) in humans. Estimates for exposure to non-SARS coronaviruses are high, particularly for 229E and OC43; however, less information regarding seroprevalence is available for HKU1 and NL63. To measure exposure rates to these four coronavirus strains (229E, HKU1, NL63, and OC43), we devised an immunoassay based on amino- and carboxy-terminally tagged recombinant coronavirus nucleocapsid antigens. Four human and one feline coronavirus antigen were cloned into baculoviruses expressed in insect cells and recovered proteins bound in the solid phase of an enzyme-linked immunosorbent assay-based system. We screened sera from 10 children and 196 adults and established primary cutoff points based on immunoglobulin G (IgG) antibody levels of the predominantly seronegative children. The proportion of seropositive adults for each coronavirus was as follows: 229E, 91.3%; HKU1, 59.2%; NL63, 91.8%; and OC43, 90.8%. No evidence of a significant serological response to the feline coronavirus was observed. Significant associations of coronavirus seropositivity and antibody levels with age, gender, race, socioeconomic status, smoking status, and season of the blood draw were tested with chi-square and regression analyses. The group II coronaviruses (OC43 and HKU1) were significantly associated with race (P ≤ 0.009 and P ≤ 0.03, respectively). Elevated OC43 IgG levels were further significantly associated with smoking status (P ≤ 0.03), as were high NL63 titers with socioeconomic status (P ≤ 0.04). The high-level immunoreactivity of each coronavirus was significantly associated with the summer season (P ≤ 0.01 to 0.0001). In summary, high rates of exposure to 229E, NL63, and OC43 and a moderate rate of exposure to HKU1 characterized the seroprevalence among individuals in this population. Demographic factors, such as race, smoking status, and socioeconomic status, may confer an increased risk of susceptibility to these viruses.",,"['Severance, Emily G.', 'Bossis, Ioannis', 'Dickerson, Faith B.', 'Stallings, Cassie R.', 'Origoni, Andrea E.', 'Sullens, Anne', 'Yolken, Robert H.', 'Viscidi, Raphael P.']",,,,
,PMC,Detection of Mumps Virus RNA by Real-Time One-Step Reverse Transcriptase PCR Using the LightCycler Platform,http://dx.doi.org/10.1128/JCM.01446-08,PMC2593261,,,"A real-time reverse transcriptase PCR (RT-PCR) assay that targeted both the mumps virus F gene and human RNase P in clinical samples was adapted for use with the LightCycler platform. LightCycler RT-PCR is as sensitive as conventional nested RT-PCR and significantly less expensive and labor-intensive, making it ideal for mumps diagnosis during outbreaks.",,"['Leblanc, Jason J.', 'Pettipas, Janice', 'Davidson, Ross J.', 'Tipples, Graham A.', 'Hiebert, Joanne', 'Hatchette, Todd F.']",,,,
,PMC,Immunopathological Basis of Lymphocytic Choriomeningitis Virus-Induced Chorioretinitis and Keratitis,http://dx.doi.org/10.1128/JVI.01211-08,PMC2612306,,,"The infection of humans with the rodent-borne lymphocytic choriomeningitis virus (LCMV) can lead to central nervous system disease in adults or severe neurological disease with hydrocephalus and chorioretinitis in children infected congenitally. Although LCMV-induced meningitis and encephalitis have been studied extensively, the immunopathological mechanisms underlying LCMV infection-associated ocular disease remain elusive. We report here that the intraocular administration of the neurotropic LCMV strain Armstrong (Arm) elicited pronounced chorioretinitis and keratitis and that infection with the more viscerotropic strains WE and Docile precipitated less severe immunopathological ocular disease. Time course analyses revealed that LCMV Arm infection of the uvea and neuroretina led to monophasic chorioretinitis which peaked between days 7 and 12 after infection. Analyses of T-cell-deficient mouse strains showed that LCMV-mediated ocular disease was strictly dependent on the presence of virus-specific CD8(+) T cells and that the contribution of CD4(+) T cells was negligible. Whereas the topical application of immunosuppressive agents did not prevent the development of chorioretinitis, passive immunization with hyperimmune sera partially prevented retinal and corneal damage. Likewise, mice displaying preexisting LCMV-specific T-cell responses were protected against LCMV-induced ocular disease. Thus, antibody- and/or T-cell-based vaccination protocols could be employed as preventive strategies against LCMV-mediated chorioretinitis.",,"['Zinkernagel, Martin S.', 'Bolinger, Beatrice', 'Krebs, Philippe', 'Onder, Lucas', 'Miller, Simone', 'Ludewig, Burkhard']",,,,
,PMC,Interferon-β expressed by a rabies virus-based HIV-1 vaccine vector serves as a molecular adjuvant and decreases pathogenicity,http://dx.doi.org/10.1016/j.virol.2008.09.019,PMC2645003,,,"Type I interferon is important in anti-viral responses and in coordinating the innate immune response. Here we explore the use of interferon-β to adjuvant the response to a rabies virus (RV) vaccine vector expressing both HIV-1 Gag and IFN-β. Viral load and immune responses of immunized mice were analyzed over time. Our results indicate that the RV expressing IFN-β (IFN(+)) is highly attenuated when compared to control RV and demonstrate that the expression of IFN-β reduces viral replication approximately 100-fold. Despite the decrease in replication, those mice immunized with the IFN(+) RV had a significantly greater number of activated CD8+ T cells. The increased activation of CD8+ T cells was dependent on IFN-β signaling, as we saw no difference following infection of IFNAR−/− mice. Although mice immunized with IFN(+) have a greater primary immune response than controls, immunized mice that were challenged with vaccinia expressing Gag had no significant difference in the number or functionality of CD8+ T cells. The increased CD8+ T cell activation in the presence of IFN-β, even with greatly reduced viral replication, indicates the beneficial effect of IFN-β for the host.",,"['Faul, Elizabeth J.', 'Wanjalla, Celestine N.', 'McGettigan, James P.', 'Schnell, Matthias J.']",,,,
,PMC,The expanding field of poly(ADP-ribosyl)ation reactions. ‘Protein Modifications: Beyond the Usual Suspects' Review Series,http://dx.doi.org/10.1038/embor.2008.191,PMC2581850,,,"Poly(ADP-ribosyl)ation is a post-translational modification of proteins that is mediated by poly(ADP-ribose) polymerases (PARPs). Although the existence and nature of the nucleic acid-like molecule poly(ADP-ribose) (PAR) has been known for 40 years, understanding its biological functions—originally thought to be only the regulation of chromatin superstructure when DNA is broken—is still the subject of intense research. Here, we review the mechanisms controlling the biosynthesis of this complex macromolecule and some of its main biological functions, with an emphasis on the most recent advances and hypotheses that have developed in this rapidly growing field.",,"['Hakmé, Antoinette', 'Wong, Heng-Kuan', 'Dantzer, Françoise', 'Schreiber, Valérie']",,,,
,PMC,T Cell Responses to Whole SARS Coronavirus in Humans,,PMC2683413,,,"Effective vaccines should confer long-term protection against future outbreaks of severe acute respiratory syndrome (SARS) caused by a novel zoonotic coronavirus (SARS-CoV) with unknown animal reservoirs. We conducted a cohort study examining multiple parameters of immune responses to SARS-CoV infection, aiming to identify the immune correlates of protection. We used a matrix of overlapping peptides spanning whole SARS-CoV proteome to determine T cell responses from 128 SARS convalescent samples by ex vivo IFN-γ ELISPOT assays. Approximately 50% of convalescent SARS patients were positive for T cell responses, and 90% possessed strongly neutralizing Abs. Fifty-five novel T cell epitopes were identified, with spike protein dominating total T cell responses. CD8(+) T cell responses were more frequent and of a greater magnitude than CD4(+) T cell responses (p < 0.001). Polychromatic cytometry analysis indicated that the virus-specific T cells from the severe group tended to be a central memory phenotype (CD27(+)/CD45RO(+)) with a significantly higher frequency of polyfunctional CD4(+) T cells producing IFN-γ, TNF-α, and IL-2, and CD8(+) T cells producing IFN-γ, TNF-α, and CD107a (degranulation), as compared with the mild-moderate group. Strong T cell responses correlated significantly (p < 0.05) with higher neutralizing Ab. The serum cytokine profile during acute infection indicated a significant elevation of innate immune responses. Increased Th2 cytokines were observed in patients with fatal infection. Our study provides a roadmap for the immunogenicity of SARS-CoV and types of immune responses that may be responsible for the virus clearance, and should serve as a benchmark for SARS-CoV vaccine design and evaluation.",,"['Li, Chris Ka-fai', 'Wu, Hao', 'Yan, Huiping', 'Ma, Shiwu', 'Wang, Lili', 'Zhang, Mingxia', 'Tang, Xiaoping', 'Temperton, Nigel J.', 'Weiss, Robin A.', 'Brenchley, Jason M.', 'Douek, Daniel C.', 'Mongkolsapaya, Juthathip', 'Tran, Bac-Hai', 'Lin, Chen-lung Steve', 'Screaton, Gavin R.', 'Hou, Jin-lin', 'McMichael, Andrew J.', 'Xu, Xiao-Ning']",,,,
,PMC,B cells from patients with Graves’ disease aberrantly express the IGF-1 receptor: Implications for disease pathogenesis,,PMC2562248,,,"Graves’ disease (GD) is an autoimmune process involving the thyroid and connective tissues in the orbit and pretibial skin. Activating anti-thyrotropin receptor Abs are responsible for hyperthyroidism in GD. But neither these auto-Abs nor the receptor they are directed against have been convincingly implicated in the connective tissue manifestations. Insulin-like growth factor-1 receptor (IGF-1R)-bearing fibroblasts over-populate connective tissues in GD and when ligated with IgGs from these patients, express the T cell chemoattractants, IL-16 and RANTES. Disproportionately large fractions of peripheral blood T cells also express IGF-1R in patients with GD, and may account, at least in part, for expansion of IGF-1R(+) memory T cells. We now report a similarly skewed B cell population exhibiting the IGF-1R(+) phenotype from the blood, orbit and bone marrow of patients with GD. This expression profile exhibits durability in culture and is maintained or increased with CpG activation. Moreover, IGF-1R(+) B cells produce pathogenic antibodies against the thyroid stimulating hormone receptor. In lymphocytes from patients with GD, IGF-1 enhanced IgG (p<0.05) production and increased B cell expansion (p<0.02) in vitro while those from control donors failed to respond. These findings suggest a potentially important role for IGF-1R display by B lymphocytes in patients with GD in supporting their expansion and abnormal immunoglobulin production.",,"['Douglas, Raymond S.', 'Naik, Vibharavi', 'Hwang, Catherine J.', 'Afifiyan, Nikoo F.', 'Gianoukakis, Andrew G.', 'Sand, Daniel', 'Kamat, Shweta', 'Smith, Terry J.']",,,,
,PMC,"Mouse Hepatitis Virus Liver Pathology Is Dependent on ADP-Ribose-1″-Phosphatase, a Viral Function Conserved in the Alpha-Like Supergroup",http://dx.doi.org/10.1128/JVI.02082-08,PMC2593347,,,"Viral infection of the liver can lead to severe tissue damage when high levels of viral replication and spread in the organ are coupled with strong induction of inflammatory responses. Here we report an unexpected correlation between the expression of a functional X domain encoded by the hepatotropic mouse hepatitis virus strain A59 (MHV-A59), the high-level production of inflammatory cytokines, and the induction of acute viral hepatitis in mice. X-domain (also called macro domain) proteins possess poly-ADP-ribose binding and/or ADP-ribose-1′′-phosphatase (ADRP) activity. They are conserved in coronaviruses and in members of the “alpha-like supergroup” of phylogenetically related positive-strand RNA viruses that includes viruses of medical importance, such as rubella virus and hepatitis E virus. By using reverse genetics, we constructed a recombinant murine coronavirus MHV-A59 mutant encoding a single-amino-acid substitution of a strictly conserved residue that is essential for coronaviral ADRP activity. We found that the mutant virus replicated to slightly reduced titers in livers but, strikingly, did not induce liver disease. In vitro, the mutant virus induced only low levels of the inflammatory cytokines tumor necrosis factor alpha and interleukin-6 (IL-6). In vivo, we found that IL-6 production, in particular, was reduced in the spleens and livers of mutant virus-infected mice. Collectively, our data demonstrate that the MHV X domain exacerbates MHV-induced liver pathology, most likely through the induction of excessive inflammatory cytokine expression.",,"['Eriksson, Klara Kristin', 'Cervantes-Barragán, Luisa', 'Ludewig, Burkhard', 'Thiel, Volker']",,,,
,PMC,The TRAPP Complex: Insights into its Architecture and Function,http://dx.doi.org/10.1111/j.1600-0854.2008.00833.x,PMC3417770,,,"Vesicle-mediated transport is a process carried out by virtually every cell and is required for the proper targeting and secretion of proteins. As such, there are numerous players involved to ensure that the proteins are properly localized. Overall, transport requires vesicle budding, recognition of the vesicle by the target membrane and fusion of the vesicle with the target membrane resulting in delivery of its contents. The initial interaction between the vesicle and the target membrane has been referred to as tethering. Because this is the first contact between the two membranes, tethering is critical to ensuring that specificity is achieved. It is therefore not surprising that there are numerous ‘tethering factors’ involved ranging from multisubunit complexes, coiled-coil proteins and Rab guanosine triphosphatases. Of the multisubunit tethering complexes, one of the best studied at the molecular level is the evolutionarily conserved TRAPP complex. There are two forms of this complex: TRAPP I and TRAPP II. In yeast, these complexes function in a number of processes including endoplasmic reticulum-to-Golgi transport (TRAPP I) and an ill-defined step at the trans Golgi (TRAPP II). Because the complex was first reported in 1998 (1), there has been a decade of studies that have clarified some aspects of its function but have also raised further questions. In this review, we will discuss recent advances in our understanding of yeast and mammalian TRAPP at the structural and functional levels and its role in disease while trying to resolve some apparent discrepancies and highlighting areas for future study.",,"['Sacher, Michael', 'Kim, Yeon-Gil', 'Lavie, Arnon', 'Oh, Byung-Ha', 'Segev, Nava']",,,,
,PMC,A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication,http://dx.doi.org/10.1073/pnas.0805240105,PMC2571001,,,"We report the discovery and optimization of a potent inhibitor against the papain-like protease (PLpro) from the coronavirus that causes severe acute respiratory syndrome (SARS-CoV). This unique protease is not only responsible for processing the viral polyprotein into its functional units but is also capable of cleaving ubiquitin and ISG15 conjugates and plays a significant role in helping SARS-CoV evade the human immune system. We screened a structurally diverse library of 50,080 compounds for inhibitors of PLpro and discovered a noncovalent lead inhibitor with an IC(50) value of 20 μM, which was improved to 600 nM via synthetic optimization. The resulting compound, GRL0617, inhibited SARS-CoV viral replication in Vero E6 cells with an EC(50) of 15 μM and had no associated cytotoxicity. The X-ray structure of PLpro in complex with GRL0617 indicates that the compound has a unique mode of inhibition whereby it binds within the S4-S3 subsites of the enzyme and induces a loop closure that shuts down catalysis at the active site. These findings provide proof-of-principle that PLpro is a viable target for development of antivirals directed against SARS-CoV, and that potent noncovalent cysteine protease inhibitors can be developed with specificity directed toward pathogenic deubiquitinating enzymes without inhibiting host DUBs.",,"['Ratia, Kiira', 'Pegan, Scott', 'Takayama, Jun', 'Sleeman, Katrina', 'Coughlin, Melissa', 'Baliji, Surendranath', 'Chaudhuri, Rima', 'Fu, Wentao', 'Prabhakar, Bellur S.', 'Johnson, Michael E.', 'Baker, Susan C.', 'Ghosh, Arun K.', 'Mesecar, Andrew D.']",,,,
,PMC,Neuroprotective Effect of Apolipoprotein D against Human Coronavirus OC43-Induced Encephalitis in Mice,http://dx.doi.org/10.1523/JNEUROSCI.2644-08.2008,PMC6671015,,,"Apolipoprotein D (apoD) is a lipocalin upregulated in the nervous system after injury or pathologies such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. We previously demonstrated that apoD protects against neuropathology by controlling the level of peroxidated lipids. Here, we further investigated the biological function of apoD in a mouse model of acute encephalitis. Our results show that apoD transcript and protein are upregulated during acute encephalitis induced by the human coronavirus OC43 (HCoV-OC43) infection. The apoD upregulation coincides with glial activation, and its expression returns to normal levels when the virus is cleared, concomitantly to a resolved glial reactivity. In addition, the overexpression of human apoD in the neurons of Thy-1/ApoD transgenic mice results in a threefold increase of the number of mice surviving to HCoV-OC43 infection. This increased survival rate is correlated with an upregulated glial activation associated with a limited innate immune response (cytokines, chemokines) and T-cell infiltration into infected brains. Moreover, the protection seems to be associated with a restricted phospholipase A2 activity. These data reveal a role for apoD in the regulation of inflammation and suggest that it protects from HCoV-OC43-induced encephalitis, most likely through the phospholipase A2 signaling pathways.",,"['Do Carmo, Sonia', 'Jacomy, Hélène', 'Talbot, Pierre J.', 'Rassart, Eric']",,,,
,PMC,Memory CD4(+) T-Cell-Mediated Protection from Lethal Coronavirus Encephalomyelitis,http://dx.doi.org/10.1128/JVI.01267-08,PMC2593339,,,"The antiviral role of CD4(+) T cells in virus-induced pathologies of the central nervous system (CNS) has not been explored extensively. Control of neurotropic mouse hepatitis virus (JHMV) requires the collaboration of CD4(+) and CD8(+) T cells, with CD8(+) T cells providing direct perforin and gamma interferon (IFN-γ)-mediated antiviral activity. To distinguish bystander from direct antiviral contributions of CD4(+) T cells in virus clearance and pathology, memory CD4(+) T cells purified from wild type (wt), perforin-deficient (PKO), and IFN-γ-deficient (GKO) immune donors were transferred to immunodeficient SCID mice prior to CNS challenge. All three donor CD4(+) T-cell populations controlled CNS virus replication at 8 days postinfection, indicating IFN-γ- and perforin-independent antiviral function. Recipients of GKO CD4(+) T cells succumbed more rapidly to fatal disease than untreated control infected mice. In contrast, wt and PKO donor CD4(+) T cells cleared infectious virus to undetectable levels and protected from fatal disease. Recipients of all CD4(+) T-cell populations exhibited demyelination. However, it was more severe in wt CD4(+) T-cell recipients. These data support a role of CD4(+) T cells in virus clearance and demyelination. Despite substantial IFN-γ-independent antiviral activity, IFN-γ was crucial in providing protection from death. IFN-γ reduced neutrophil accumulation and directed macrophages to white matter but did not ameliorate myelin loss.",,"['Savarin, Carine', 'Bergmann, Cornelia C.', 'Hinton, David R.', 'Ransohoff, Richard M.', 'Stohlman, Stephen A.']",,,,
,PMC,Topology and Membrane Anchoring of the Coronavirus Replication Complex: Not All Hydrophobic Domains of nsp3 and nsp6 Are Membrane Spanning,http://dx.doi.org/10.1128/JVI.01219-08,PMC2593338,,,"Coronaviruses express two very large replicase polyproteins, the 16 autoproteolytic cleavage products of which collectively form the membrane-anchored replication complexes. How these structures are assembled is still largely unknown, but it is likely that the membrane-spanning members of these nonstructural proteins (nsps) are responsible for the induction of the double-membrane vesicles and for anchoring the replication complexes to these membranes. For 3 of the 16 coronavirus nsps—nsp3, nsp4, and nsp6—multiple transmembrane domains are predicted. Previously we showed that, consistent with predictions, nsp4 occurs in membranes with both of its termini exposed in the cytoplasm (M. Oostra et al., J. Virol. 81:12323-12336, 2007). Strikingly, however, for both nsp3 and nsp6, predictions based on a multiple alignment of 27 coronavirus genome sequences indicate an uneven number of transmembrane domains. As a consequence, the proteinase domains present in nsp3 and nsp5 would be separated from their target sequences by the lipid bilayer. To look into this incongruity, we studied the membrane disposition of nsp3 and nsp6 of the severe acute respiratory syndrome coronavirus and murine hepatitis virus by analyzing tagged forms of the proteins expressed in cultured cells. Contrary to the predictions, in both viruses, both proteins had their amino terminus, as well as their carboxy terminus, exposed in the cytoplasm. We established that two of the three hydrophobic domains in nsp3 and six of the seven in nsp6 are membrane spanning. Subsequently, we verified that in nsp4, all four hydrophobic domains span the lipid bilayer. The occurrence of conserved non-membrane-spanning hydrophobic domains in nsp3 and nsp6 suggests an important function for these domains in coronavirus replication.",,"['Oostra, Monique', 'Hagemeijer, Marne C.', 'van Gent, Michiel', 'Bekker, Cornelis P. J.', 'te Lintelo, Eddie G.', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.']",,,,
,PMC,"Acute infections, vaccination and prevention of cardiovascular disease",http://dx.doi.org/10.1503/cmaj.081302,PMC2553865,,,,,"Madjid, Mohammad",,,,
,PMC,"Effects of smoking and solid-fuel use on COPD, lung cancer, and tuberculosis in China: a time-based, multiple risk factor, modelling study",http://dx.doi.org/10.1016/S0140-6736(08)61345-8,PMC2652750,,,"BACKGROUND: Chronic obstructive pulmonary disease (COPD), lung cancer, and tuberculosis are three leading causes of death in China, where prevalences of smoking and solid-fuel use are also high. We aimed to predict the effects of risk-factor trends on COPD, lung cancer, and tuberculosis. METHODS: We used representative data sources to estimate past trends in smoking and household solid-fuel use and to construct a range of future scenarios. We obtained the aetiological effects of risk factors on diseases from meta-analyses of epidemiological studies and from large studies in China. We modelled future COPD and lung cancer mortality and tuberculosis incidence, taking into account the accumulation of hazardous effects of risk factors on COPD and lung cancer over time, and dependency of the risk of tuberculosis infection on the prevalence of disease. We quantified the sensitivity of our results to methods and data choices. FINDINGS: If smoking and solid-fuel use remain at current levels between 2003 and 2033, 65 million deaths from COPD and 18 million deaths from lung cancer are predicted in China; 82% of COPD deaths and 75% of lung cancer deaths will be attributable to the combined effects of smoking and solid-fuel use. Complete gradual cessation of smoking and solid-fuel use by 2033 could avoid 26 million deaths from COPD and 6·3 million deaths from lung cancer; interventions of intermediate magnitude would reduce deaths by 6−31% (COPD) and 8−26% (lung cancer). Complete cessation of smoking and solid-fuel use by 2033 would reduce the projected annual tuberculosis incidence in 2033 by 14−52% if 80% DOTS coverage is sustained, 27−62% if 50% coverage is sustained, or 33−71% if 20% coverage is sustained. INTERPRETATION: Reducing smoking and solid-fuel use can substantially lower predictions of COPD and lung cancer burden and would contribute to effective tuberculosis control in China. FUNDING: International Union Against Tuberculosis and Lung Disease.",,"['Lin, Hsien-Ho', 'Murray, Megan', 'Cohen, Ted', 'Colijn, Caroline', 'Ezzati, Majid']",,,,
,PMC,"Overexpression of NANOG in Gestational Trophoblastic Diseases : Effect on Apoptosis, Cell Invasion, and Clinical Outcome",http://dx.doi.org/10.2353/ajpath.2008.080288,PMC2543083,,,"Gestational trophoblastic disease includes choriocarcinoma, a frankly malignant tumor, and hydatidiform mole (HM), which often leads to the development of persistent gestational trophoblastic neoplasia and requires chemotherapy. NANOG is an important transcription factor that is crucial for maintaining embryonic stem cell self-renewal and pluripotency. We postulated that NANOG is involved in the pathogenesis of gestational trophoblastic disease. In this study, significantly higher NANOG mRNA and protein expression levels, by quantitative PCR and immunoblotting, respectively, were demonstrated in HMs, particularly those that developed persistent disease, when compared with normal placentas. In addition, significantly increased nuclear NANOG immunoreactivity was found by immunohistochemistry in HMs (P < 0.001) and choriocarcinoma (P = 0.002). Higher NANOG expression levels were demonstrated in HMs that developed persistent disease, as compared with those that regressed (P = 0.025). Nuclear localization of NANOG was confirmed by confocal microscopy and immunoblotting in choriocarcinoma cell lines. There was a significant inverse correlation between NANOG immunoreactivity and apoptotic index assessed by M30 CytoDeath antibody (P = 0.012). After stable knockdown of NANOG in the choriocarcinoma cell line JEG-3 by an shRNA approach, increased apoptosis was observed in relation to with enhanced caspases and poly(ADP-ribose) polymerase activities. NANOG knockdown was also associated with decreased mobility and invasion of JEG-3 and down-regulation of matrix metalloproteases 2 and 9. These findings suggest that NANOG is involved in the pathogenesis and clinical progress of gestational trophoblastic disease, likely through its effect on apoptosis, cell migration, and invasion.",,"['Siu, Michelle K.Y.', 'Wong, Esther S.Y.', 'Chan, Hoi Yan', 'Ngan, Hextan Y.S.', 'Chan, Kelvin Y.K.', 'Cheung, Annie N.Y.']",,,,
,PMC,Avian influenza: The tip of the iceberg,http://dx.doi.org/10.4103/1817-1737.43085,PMC2700449,19561900,CC BY,"For some years now, we have been living with the fear of an impending pandemic of avian influenza (AI). Despite the recognition, in 1996, of the global threat posed by the highly pathogenic H5N1 influenza virus found in farmed geese in Guangdong Province, China, planning for the anticipated epidemic remains woefully inadequate; this is especially true in developing countries such as Saudi Arabia. These deficiencies became obvious in 1997, with the outbreak of AI in the live animal markets in Hong Kong that led to the transmission of infection to 18 humans with close contact with diseased birds; there were six reported deaths.[1] In 2003, with the reemergence of H5N1 (considered the most likely AI virus) in the Republic of Korea and its subsequent spread to Thailand, Vietnam, Hong Kong and China. Many countries started aggressively making preparations to meet the threat.[2] The pressure for real action from governments has increased. Most developed countries have requested increased funding for the search for a more effective vaccine, for stockpiling possibly helpful antiviral drugs, and for intensifying domestic and global surveillance.[3] Most countries, however, continue to be inadequately prepared for such an epidemic, especially with regard to animal surveillance in the farm market and surveillance among migratory birds. Even now, most countries do not have the ability to detect disease among humans in the early stages of an outbreak nor do most hospitals comply with effective infection control measures that could curtail the spread of the virus in the early stages of an epidemic. In Saudi Arabia we are rapidly implementing many of these measures.[4]",2008 Oct-Dec,"Balkhy, Hanan",Ann Thorac Med,,,
,PMC,Strategies for the Identification of novel inhibitors of deubiquitinating enzymes,http://dx.doi.org/10.1042/BST0360828,PMC3061546,,,"Dysregulation of the ubiquitin-proteasome system (UPS) has been implicated in a wide range of pathologies including cancer, neurodegeneration, and viral infection. Inhibiting the proteasome has been shown to be an effective therapeutic strategy in humans; yet toxicity with this target remains high. Deubiquitinating enzymes (DUBs) represent an alternative target in the UPS with low predicted toxicity. Currently, there are no DUB inhibitors that have entered the clinic. To address this situation, Progenra has developed a novel assay to measure the proteolytic cleavage of ubiquitin or UBL (ubiquitin like protein) conjugates such as SUMO, NEDD8 or ISG15 by isopeptidases. Here we will discuss current platforms for detecting DUB inhibitors and underline the advantages and disadvantages of the approaches.",,"['Goldenberg, Seth J', 'McDermott, Jeffrey L', 'Butt, Tauseef R', 'Mattern, Michael R', 'Nicholson, Benjamin']",,,,
,PMC,Analytical sensitivity of air samplers based on uniform point-source exposure to airborne Porcine reproductive and respiratory syndrome virus and swine influenza virus,,PMC2568049,,,"Research and surveillance activities involving airborne pathogens rely on the capture and enumeration of pathogens suspended in aerosols. The objective of this study was to estimate the analytical sensitivity (detection threshold) of each of 4 air samplers for Porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SIV). In a 5-min sampling period under controlled conditions, the analytical sensitivity of the AGI-30 (Ace Glass, Vineland, New Jersey, USA), AGI-4 (Ace Glass), SKC BioSampler (SKC, Eighty Four, Pennsylvania, USA), and Midwest Micro-Tek sampler (Midwest Micro-Tek, Brookings, South Dakota, USA) was calculated at 1 × 10(1.1), 1 × 10(1.3), 1 × 10(1.1), and 1 × 10(1.2) median tissue culture infectious dose (TCID(50)) equivalents for PRRSV and 1 × 10(1.4), 1 × 10(1.1), 1 × 10(1.6), and 1 × 10(1.2) TCID(50) equivalents for SIV [per 60 L (5-min sampling period)]. Despite marked differences in sampler design, no statistically significant difference in analytical sensitivity was detected between the samplers for collection of artificially produced aerosols containing cell-culture-propagated PRRSV or SIV.",,"['Hermann, Joseph R.', 'Zimmerman, Jeffrey J.']",,,,
,PMC,Pathogenicity of infectious bronchitis virus isolates from Ontario chickens,,PMC2568044,,,"Infectious bronchitis (IB) is one of the important viral diseases of chickens, and in spite of regular vaccination, IB is a continuous problem in Canadian poultry operations. In an earlier study using sentinel chickens we determined the incidence of infectious bronchitis virus (IBV) in Ontario commercial layer flocks. The objective of this study was to determine the pathogenicity of 5 nonvaccine-related IBV isolates recovered from the sentinel birds. The clinical signs, gross, and histological lesions in specific pathogen-free chickens indicated that all 5 isolates caused mild lesions in the respiratory tract. An important finding of this study was the significantly lower average daily weight gain among virus-inoculated groups of chickens during the acute phase of infection. Based on sequences of part of the S1 gene IBV-ON2, IBV-ON3, and IBV-ON5 formed a cluster and they were closely related to strain CU-82792. IBV-ON4 had 98.7% identity with the strain PA/1220/9, a nephropathogenic variant.",,"['Grgiæ, Helena', 'Hunter, D. Bruce', 'Hunton, Peter', 'Nagy, Éva']",,,,
,PMC,"Emergence and Disappearance of a Virulent Clone of Haemophilus influenzae Biogroup aegyptius, Cause of Brazilian Purpuric Fever",http://dx.doi.org/10.1128/CMR.00020-08,PMC2570154,,,"Summary: In 1984, children presented to the emergency department of a hospital in the small town of Promissão, São Paulo State, Brazil, with an acute febrile illness that rapidly progressed to death. Local clinicians and public health officials recognized that these children had an unusual illness, which led to outbreak investigations conducted by Brazilian health officials in collaboration with the U.S. Centers for Disease Control and Prevention. The studies that followed are an excellent example of the coordinated and parallel studies that are used to investigate outbreaks of a new disease, which became known as Brazilian purpuric fever (BPF). In the first outbreak investigation, a case-control study confirmed an association between BPF and antecedent conjunctivitis but the etiology of the disease could not be determined. In a subsequent outbreak, children with BPF were found to have bacteremia caused by Haemophilus influenzae biogroup aegyptius (H. aegyptius), an organism previously known mainly to cause self-limited purulent conjunctivitis. Molecular characterization of blood and other isolates demonstrated the clonal nature of the H. aegyptius strains that caused BPF, which were genetically distant from the diverse strains that cause only conjunctivitis. This led to an intense effort to identify the factors causing the unusual invasiveness of the BPF clone, which has yet to definitively identify the virulence factor or factors involved. After a series of outbreaks and sporadic cases through 1993, no additional cases of BPF have been reported.",,"['Harrison, Lee H.', 'Simonsen, Vera', 'Waldman, Eliseu A.']",,,,
,PMC,Detection of Respiratory Viruses by Molecular Methods,http://dx.doi.org/10.1128/CMR.00037-07,PMC2570148,,,"Summary: Clinical laboratories historically diagnose seven or eight respiratory virus infections using a combination of techniques including enzyme immunoassay, direct fluorescent antibody staining, cell culture, and nucleic acid amplification tests. With the discovery of six new respiratory viruses since 2000, laboratories are faced with the challenge of detecting up to 19 different viruses that cause acute respiratory disease of both the upper and lower respiratory tracts. The application of nucleic acid amplification technology, particularly multiplex PCR coupled with fluidic or fixed microarrays, provides an important new approach for the detection of multiple respiratory viruses in a single test. These multiplex amplification tests provide a sensitive and comprehensive approach for the diagnosis of respiratory tract infections in individual hospitalized patients and the identification of the etiological agent in outbreaks of respiratory tract infection in the community. This review describes the molecular methods used to detect respiratory viruses and discusses the contribution that molecular testing, especially multiplex PCR, has made to our ability to detect respiratory viruses and to increase our understanding of the roles of various viral agents in acute respiratory disease.",,"Mahony, James B.",,,,
,PMC,Career Opportunities for Me?,http://dx.doi.org/10.3325/cmj.2008.5.684,PMC2582363,,,,,"Calisher, Charles H.",,,,
,PMC,Altered endochondral ossification in collagen X mouse models leads to impaired immune responses,http://dx.doi.org/10.1002/dvdy.21594,PMC2630710,,,"Disruption of collagen X function in hypertrophic cartilage undergoing endochondral ossification was previously linked to altered hematopoiesis in collagen X transgenic (Tg) and null (KO) mice (Jacenko et al., 2002). Mice displayed altered growth plates, diminished trabecular bone, and marrow hypoplasia with an aberrant lymphocyte profile throughout life. This study identifies altered B220(+), CD4(+), and CD8(+) lymphocyte numbers, as well as CD4(+)/fox3P(+) T regulatory cells in the collagen X mice. Additionally, diminished in vitro splenocyte responses to mitogens and an inability of mice to survive a challenge with Toxoplasma gondii, confirm impaired immune responses. In concert, ELISA and protein arrays identify aberrant levels of inflammatory, chemo-attractant, and matrix binding cytokines in collagen X mouse sera. These data link the disruption of collagen X function in the chondro-osseous junction to an altered hematopoietic stem cell niche in the marrow, resulting in impaired immune function.",,"['Sweeney, E.', 'Campbell, M.', 'Watkins, K.', 'Hunter, C.A.', 'Jacenko, O.']",,,,
,PMC,Viral vigilance. New surveillance strategies and methods help to identify dangerous pathogens earlier: a prerequisite for efficient countermeasures,http://dx.doi.org/10.1038/embor.2008.181,PMC2572123,,,,,"Hunter, Philip",,,,
,PMC,Induction of Incomplete Autophagic Response by Hepatitis C Virus via the Unfolded Protein Response,http://dx.doi.org/10.1002/hep.22464,PMC2562598,,,"Autophagy is important for cellular homeostasis and can serve as innate immunity to remove intracellular pathogens. Here we demonstrate by a battery of morphological and biochemical assays that HCV induces the accumulation of autophagosomes in cells without enhancing autophagic protein degradation. This induction of autophagosomes depended on the unfolded protein response (UPR), as the suppression of UPR signaling pathways suppressed HCV-induced lipidation of the LC3 protein, a necessary step for the formation of autophagosomes. The suppression of UPR or the suppression of expression of LC3 or Atg7, a protein that mediates LC3 lipidation, suppressed HCV replication, indicating a positive role of UPR and the incomplete autophagic response in HCV replication. Conclusion: Our studies delineate the molecular pathway by which HCV induces autophagic vacuoles and also demonstrate the perturbation of the autophagic response by HCV. These unexpected effects of HCV on the host cell likely play an important role in HCV pathogenesis.",,"['Sir, Donna', 'Chen, Wen-ling', 'Choi, Jinah', 'Wakita, Takaji', 'Yen, T.S. Benedict', 'Ou, Jing-hsiung James']",,,,
,PMC,Multiplex MassTag-PCR for Respiratory Pathogens in Pediatric Nasopharyngeal Washes Negative by Conventional Diagnostic Testing Shows a High Prevalence of Viruses Belonging to a Newly Recognized Picornavirus Clade,http://dx.doi.org/10.1016/j.jcv.2008.06.007,PMC2603178,,,"BACKGROUND: Respiratory infections are the most common infectious diseases in humans worldwide and are a leading cause of death in children less than 5 years of age. OBJECTIVES: Identify candidate pathogens in pediatric patients with unexplained respiratory disease. STUDY DESIGN: Forty-four nasopharyngeal washes collected during the 2004-05 winter season from pediatric patients with respiratory illnesses that tested negative for 7 common respiratory pathogens by culture and direct immunofluorescence assays were analyzed by MassTag-PCR. To distinguish human enteroviruses (HEV) and rhinoviruses (HRV), samples positive for picornaviruses were further characterized by sequence analysis. RESULTS: Candidate pathogens were detected by MassTag PCR in 27 of the 44 (61%) specimens that previously were rated negative. Sixteen of these 27 specimens (59%) contained picornaviruses; of these 9 (57%) contained RNA of a recently discovered clade of rhinoviruses. Bocaviruses were detected in three patients by RT-PCR. CONCLUSIONS: Our study confirms that multiplex MassTag-PCR enhances the detection of pathogens in clinical specimens, and shows that previously unrecognized rhinoviruses, that potentially form a species HRV-C, may cause a significant amount of pediatric respiratory disease.",,"['Dominguez, Samuel R.', 'Briese, Thomas', 'Palacios, Gustavo', 'Hui, Jeffrey', 'Villari, Joseph', 'Kapoor, Vishal', 'Tokarz, Rafal', 'Glodé, Mary P.', 'Anderson, Marsha S.', 'Robinson, Christine C.', 'Holmes, Kathryn V.', 'Lipkin, W. Ian']",,,,
,PMC,What Are the Risks—Hypothetical and Observed—of Recombination Involving Live Vaccines and Vaccine Vectors Based on Nonsegmented Negative-Strain RNA Viruses?,http://dx.doi.org/10.1128/JVI.01336-08,PMC2546970,,,,,"['Collins, Peter L.', 'Bukreyev, Alexander', 'Murphy, Brian R.']",,,,
,PMC,Translationally Repressed mRNA Transiently Cycles through Stress Granules during Stress,http://dx.doi.org/10.1091/mbc.E08-05-0499,PMC2555929,,,"In mammals, repression of translation during stress is associated with the assembly of stress granules in the cytoplasm, which contain a fraction of arrested mRNA and have been proposed to play a role in their storage. Because physical contacts are seen with GW bodies, which contain the mRNA degradation machinery, stress granules could also target arrested mRNA to degradation. Here we show that contacts between stress granules and GW bodies appear during stress-granule assembly and not after a movement of the two preassembled structures. Despite this close proximity, the GW body proteins, which in some conditions relocalize in stress granules, come from cytosol rather than from adjacent GW bodies. It was previously reported that several proteins actively traffic in and out of stress granules. Here we investigated the behavior of mRNAs. Their residence time in stress granules is brief, on the order of a minute, although stress granules persist over a few hours after stress relief. This short transit reflects rapid return to cytosol, rather than transfer to GW bodies for degradation. Accordingly, most arrested mRNAs are located outside stress granules. Overall, these kinetic data do not support a direct role of stress granules neither as storage site nor as intermediate location before degradation.",,"['Mollet, Stephanie', 'Cougot, Nicolas', 'Wilczynska, Ania', 'Dautry, François', 'Kress, Michel', 'Bertrand, Edouard', 'Weil, Dominique']",,,,
,PMC,The sweeter side of ACE2: Physiological evidence for a role in diabetes,http://dx.doi.org/10.1016/j.mce.2008.09.020,PMC2676688,,,"Diabetes mellitus is a growing problem in all parts of the world. Both clinical trials and animal models of type I and type II diabetes have shown that hyperactivity of angiotensin-II (Ang-II) signaling pathways contribute to the development of diabetes and diabetic complications. Of clinical relevance, blockade of the renin–angiotensin system prevents new-onset diabetes and reduces the risk of diabetic complications. Angiotensin-converting enzyme (ACE) 2 is a recently discovered mono-carboxypeptidase and the first homolog of ACE. It is thought to inhibit Ang-II signaling cascades mostly by cleaving Ang-II to generate Ang-(1−7), which effects oppose Ang-II and are mediated by the Mas receptor. The enzyme is present in the kidney, liver, adipose tissue and pancreas. Its expression is elevated in the endocrine pancreas in diabetes and in the early phase during diabetic nephropathy. ACE2 is hypothesized to act in a compensatory manner in both diabetes and diabetic nephropathy. Recently, we have shown the presence of the Mas receptor in the mouse pancreas and observed a reduction in Mas receptor immuno-reactivity as well as higher fasting blood glucose levels in ACE2 knockout mice, indicating that these mice may be a new model to study the role of ACE2 in diabetes. In this review we will examine the role of the renin–angiotensin system in the physiopathology and treatment of diabetes and highlight the potential benefits of the ACE2/Ang-(1−7)/Mas receptor axis, focusing on recent data about ACE2.",,"['Bindom, Sharell M.', 'Lazartigues, Eric']",,,,
,PMC,Translational Research: Forging a New Cultural Identity,http://dx.doi.org/10.1002/msj.20064,PMC2691712,,,"More than a decade ago, Dr. Joseph Goldstein called attention to the increasing dissociation between scientific advances and their translation into improved health with his pithy analysis of the biotechnology industry: “1 new gene per day, 1 new company per week, 1 new drug per year.”1 Unfortunately, the gap continues to grow, with increasing concerns about whether the enormous increase in knowledge brought about by the sequencing of the human genome and other scientific advances are being matched by the translational effort. For example, a recent review by the Congressional Budget Office found that the dramatic increase in inflation-adjusted funding of biomedical research since 1970 by the pharmaceutical industry and the National Institutes of Health (NIH), in addition to the influx of capital from the biotechnology industry, has had only a minor impact on the number of truly new drugs approved by the Food and Drug Administration each year.2 The outlook for the immediate future does not appear to be much brighter, with declining numbers of new drugs being submitted for regulatory approval3 and the investment community expressing grave concerns about the prospects for both the biotechnology and pharmaceutical industries.4,5 It is not surprising, therefore, that there has been intense focus on how to successfully bridge the gap between scientific discovery and the development of new strategies to diagnose, treat, and prevent disease; this process is now commonly called translational research.",,"Coller, Barry S.",,,,
,PMC,DNA vaccines: ready for prime time?,http://dx.doi.org/10.1038/nrg2432,PMC4317294,,,"Since the discovery, over a decade and a half ago, that genetically engineered DNA can be delivered in vaccine form and elicit an immune response, there has been much progress in understanding the basic biology of this platform. A large amount of data has been generated in preclinical model systems, and more sustained cellular responses and more consistent antibody responses are being observed in the clinic. Four DNA vaccine products have recently been approved, all in the area of veterinary medicine. These results suggest a productive future for this technology as more optimized constructs, better trial designs and improved platforms are being brought into the clinic.",,"['Kutzler, Michele A.', 'Weiner, David B.']",,,,
,PMC,Single-step affinity purification of recombinant proteins using a self-excising module from Neisseria meningitidis FrpC,http://dx.doi.org/10.1110/ps.035733.108,PMC2548358,,,"Purification of recombinant proteins is often a challenging process involving several chromatographic steps that must be optimized for each target protein. Here, we developed a self-excising module allowing single-step affinity chromatography purification of untagged recombinant proteins. It consists of a 250-residue-long self-processing module of the Neisseria meningitidis FrpC protein with a C-terminal affinity tag. The N terminus of the module is fused to the C terminus of a target protein of interest. Upon binding of the fusion protein to an affinity matrix from cell lysate and washing out contaminating proteins, site-specific cleavage of the Asp–Pro bond linking the target protein to the self-excising module is induced by calcium ions. This results in the release of the target protein with only a single aspartic acid residue added at the C terminus, while the self-excising affinity module remains trapped on the affinity matrix. The system was successfully tested with several target proteins, including glutathione-S-transferase, maltose-binding protein, β-galactosidase, chloramphenicol acetyltransferase, and adenylate cyclase, and two different affinity tags, chitin-binding domain or poly-His. Moreover, it was demonstrated that it can be applied as an alternative to two currently existing systems, based on the self-splicing intein of Saccharomyces cerevisiae and sortase A of Staphylococcus aureus.",,"['Sadilkova, Lenka', 'Osicka, Radim', 'Sulc, Miroslav', 'Linhartova, Irena', 'Novak, Petr', 'Sebo, Peter']",,,,
,PMC,"Single-dose, virus-vectored vaccine protection against Yersinia pestis challenge: CD4+ cells are required at the time of challenge for optimal protection",http://dx.doi.org/10.1016/j.vaccine.2008.09.031,PMC2628553,,,"We have developed an experimental recombinant vesicular stomatitis virus (VSV) vectored plague vaccine expressing a secreted form of Yersinia pestis LcrV protein from the first position of the VSV genome. This vector, given intramuscularly in a single dose, induced high-level antibody titers to LcrV and gave 90–100% protection against pneumonic plague challenge in mice. This single-dose protection was significantly better than that generated by VSV expressing the non–secreted LcrV protein. Increased protection correlated with increased anti-LcrV antibody and a bias toward IgG2a and away from IgG1 isotypes. We also found that depletion of CD4(+) cells, but not CD8(+) cells, at the time of challenge resulted in reduced vaccine protection, indicating a role for cellular immunity in protection.",,"['Chattopadhyay, Anasuya', 'Park, Steven', 'Delmas, Guillaume', 'Suresh, Rema', 'Senina, Svetlana', 'Perlin, David S.', 'Rose, John K.']",,,,
,PMC,Mouse mammary tumor virus uses mouse but not human transferrin receptor 1 to reach a low pH compartment and infect cells,http://dx.doi.org/10.1016/j.virol.2008.08.013,PMC2641025,,,"Mouse mammary tumor virus (MMTV) is a pH-dependent virus that uses mouse transferrin receptor 1 (TfR1) for entry into cells. Previous studies demonstrated that MMTV could induce pH 5-dependent fusion-from-without of mouse cells. Here we show that the MMTV envelope-mediated cell-cell fusion requires both the entry receptor and low pH (pH 5). Although expression of the MMTV envelope and TfR1 was sufficient to mediate low pH-dependent syncytia formation, virus infection required trafficking to a low pH compartment; infection was independent of cathepsin-mediated proteolysis. Human TfR1 did not support virus infection, although envelope-mediated syncytia formation occurred with human cells after pH 5 treatment and this fusion depended on TfR1 expression. However, although the MMTV envelope bound human TfR1, virus was only internalized and trafficked to a low pH compartment in cells expressing mouse TfR1. Thus, while human TfR1 supported cell-cell fusion, because it was not internalized when bound to MMTV, it did not function as an entry receptor. Our data suggest that MMTV uses TfR1 for all steps of entry: cell attachment, induction of the conformational changes in Env required for membrane fusion and internalization to an appropriate acidic compartment.",,"['Wang, Enxiu', 'Obeng-Adjei, Nyamekye', 'Ying, Qihua', 'Meertens, Laurent', 'Dragic, Tanya', 'Davey, Robert A.', 'Ross, Susan R.']",,,,
,PMC,Contribution of Redox Status to Hepatitis C Virus E2 Envelope Protein  Function and Antigenicity,http://dx.doi.org/10.1074/jbc.M805221200,PMC3258924,,,"Disulfide bonding contributes to the function and antigenicity of many viral envelope glycoproteins. We assessed here its significance for the hepatitis C virus E2 envelope protein and a counterpart deleted for hypervariable region-1 (HVR1). All 18 cysteine residues of the antigens were involved in disulfides. Chemical reduction of up to half of these disulfides was compatible with anti-E2 monoclonal antibody reaction, CD81 receptor binding, and viral entry, whereas complete reduction abrogated these properties. The addition of 5,5′-dithiobis-2-nitrobenzoic acid had no effect on viral entry. Thus, E2 function is only weakly dependent on its redox status, and cell entry does not require redox catalysts, in contrast to a number of enveloped viruses. Because E2 is a major neutralizing antibody target, we examined the effect of disulfide bonding on E2 antigenicity. We show that reduction of three disulfides, as well as deletion of HVR1, improved antibody binding for half of the patient sera tested, whereas it had no effect on the remainder. Small scale immunization of mice with reduced E2 antigens greatly improved serum reactivity with reduced forms of E2 when compared with immunization using native E2, whereas deletion of HVR1 only marginally affected the ability of the serum to bind the redox intermediates. Immunization with reduced E2 also showed an improved neutralizing antibody response, suggesting that potential epitopes are masked on the disulfide-bonded antigen and that mild reduction may increase the breadth of the antibody response. Although E2 function is surprisingly independent of its redox status, its disulfide bonds mask antigenic domains. E2 redox manipulation may contribute to improved vaccine design.",,"['Fenouillet, Emmanuel', 'Lavillette, Dimitri', 'Loureiro, Silvia', 'Krashias, George', 'Maurin, Guillemette', 'Cosset, François-Loïc', 'Jones, Ian M.', 'Barbouche, Rym']",,,,
,PMC,A SARS DNA Vaccine Induces Neutralizing Antibody and Cellular Immune Responses in Healthy Adults in a Phase I Clinical Trial,http://dx.doi.org/10.1016/j.vaccine.2008.09.026,PMC2612543,,,"BACKGROUND: The severe acute respiratory syndrome (SARS) virus is a member of the Coronaviridae (CoV) family that first appeared in the Guangdong Province of China in 2002 and was recognized as an emerging infectious disease in March 2003. Over 8,000 cases and 900 deaths occurred during the epidemic. We report the safety and immunogenicity of a SARS DNA vaccine in a Phase I human study. METHODS: A single-plasmid DNA vaccine encoding the Spike (S) glycoprotein was evaluated in 10 healthy adults. Nine subjects completed the 3 dose vaccination schedule and were evaluated for vaccine safety and immune responses. Immune response was assessed by intracellular cytokine staining (ICS), ELISpot, ELISA, and neutralization assays. RESULTS: The vaccine was well-tolerated. SARS-CoV-specific antibody was detected by ELISA in 8 of 10 subjects and neutralizing antibody was detected in all subjects who received 3 doses of vaccine. SARS-CoV-specific CD4+ T cell responses were detected in all vaccinees, and CD8+ T cell responses in ∼20% of individuals. CONCLUSIONS: The VRC SARS DNA vaccine was well tolerated and produced cellular immune responses and neutralizing antibody in healthy adults.",,"['Martin, Julie E.', 'Louder, Mark K.', 'Holman, LaSonji A.', 'Gordon, Ingelise J.', 'Enama, Mary E.', 'Larkin, Brenda D.', 'Andrews, Charla A.', 'Vogel, Leatrice', 'Koup, Richard A.', 'Roederer, Mario', 'Bailer, Robert T.', 'Gomez, Phillip L.', 'Nason, Martha', 'Mascola, John R.', 'Nabel, Gary J.', 'Graham, Barney S.', None]",,,,
,PMC,Systematic Assembly of a Full-Length Infectious Clone of Human Coronavirus NL63,http://dx.doi.org/10.1128/JVI.01804-08,PMC2583659,,,"Historically, coronaviruses were predominantly associated with mild upper respiratory disease in humans. More recently, three novel coronaviruses associated with severe human respiratory disease were found, including (i) the severe acute respiratory syndrome coronavirus, associated with a significant atypical pneumonia and 10% mortality; (ii) HKU-1, associated with chronic pulmonary disease; and (iii) NL63, associated with both upper and lower respiratory tract disease in children and adults worldwide. These discoveries establish coronaviruses as important human pathogens and underscore the need for continued research toward the development of platforms that will enable genetic manipulation of the viral genome, allowing for rapid and rational development and testing of candidate vaccines, vaccine vectors, and therapeutics. In this report, we describe a reverse genetics system for NL63, whereby five contiguous cDNAs that span the entire genome were used to generate a full-length cDNA. Recombinant NL63 viruses which contained the expected marker mutations replicated as efficiently as the wild-type NL63 virus. In addition, we engineered the heterologous green fluorescent protein gene in place of open reading frame 3 (ORF3) of the NL63 clone, simultaneously creating a unique marker for NL63 infection and demonstrating that the ORF3 protein product is nonessential for the replication of NL63 in cell culture. The availability of the NL63 and NL63gfp clones and recombinant viruses provides powerful tools that will help advance our understanding of this important human pathogen.",,"['Donaldson, Eric F.', 'Yount, Boyd', 'Sims, Amy C.', 'Burkett, Susan', 'Pickles, Raymond J.', 'Baric, Ralph S.']",,,,
,PMC,Crystal Structure and Carbohydrate Analysis of Nipah Virus Attachment Glycoprotein: a Template for Antiviral and Vaccine Design,http://dx.doi.org/10.1128/JVI.01344-08,PMC2583688,,,"Two members of the paramyxovirus family, Nipah virus (NiV) and Hendra virus (HeV), are recent additions to a growing number of agents of emergent diseases which use bats as a natural host. Identification of ephrin-B2 and ephrin-B3 as cellular receptors for these viruses has enabled the development of immunotherapeutic reagents which prevent virus attachment and subsequent fusion. Here we present the structural analysis of the protein and carbohydrate components of the unbound viral attachment glycoprotein of NiV glycoprotein (NiV-G) at a 2.2-Å resolution. Comparison with its ephrin-B2-bound form reveals that conformational changes within the envelope glycoprotein are required to achieve viral attachment. Structural differences are particularly pronounced in the 579-590 loop, a major component of the ephrin binding surface. In addition, the 236-245 loop is rather disordered in the unbound structure. We extend our structural characterization of NiV-G with mass spectrometric analysis of the carbohydrate moieties. We demonstrate that NiV-G is largely devoid of the oligomannose-type glycans that in viruses such as human immunodeficiency virus type 1 and Ebola virus influence viral tropism and the host immune response. Nevertheless, we find putative ligands for the endothelial cell lectin, LSECtin. Finally, by mapping structural conservation and glycosylation site positions from other members of the paramyxovirus family, we suggest the molecular surface involved in oligomerization. These results suggest possible pathways of virus-host interaction and strategies for the optimization of recombinant vaccines.",,"['Bowden, Thomas A.', 'Crispin, Max', 'Harvey, David J.', 'Aricescu, A. Radu', 'Grimes, Jonathan M.', 'Jones, E. Yvonne', 'Stuart, David I.']",,,,
,PMC,"Murine Coronaviruses Encoding nsp2 at Different Genomic Loci Have Altered Replication, Protein Expression, and Localization",http://dx.doi.org/10.1128/JVI.01126-07,PMC2583644,,,"Partial or complete deletion of several coronavirus nonstructural proteins (nsps), including open reading frame 1a (ORF1a)-encoded nsp2, results in viable mutant proteins with specific replication defects. It is not known whether expression of nsps from alternate locations in the genome can complement replication defects. In this report, we show that the murine hepatitis virus nsp2 sequence was tolerated in ORF1b with an in-frame insertion between nsp13 and nsp14 and in place of ORF4. Alternate encoding or duplication of the nsp2 gene sequence resulted in differences in nsp2 expression, processing, and localization, was neutral or detrimental to replication, and did not complement an ORF1a Δnsp2 replication defect. The results suggest that wild-type genomic organization and expression of nsps are required for optimal replication.",,"['Gadlage, Mark J.', 'Graham, Rachel L.', 'Denison, Mark R.']",,,,
,PMC,"High-Throughput Screening of a 100,000 Compound Library for Inhibitors of Influenza A virus (H3N2)",http://dx.doi.org/10.1177/1087057108323123,PMC2782602,,,"Using a highly reproducible and robust cell-based HTS assay, the authors screened a 100,000 compound library at 14 and 114 μM compound concentration against influenza strain A/Udorn/72 (H3N2). The “hit” rates (>50% inhibition of the viral cytopathic effect) from the 14 and 114 μM screens were 0.022% and 0.38%, respectively. The hits were evaluated for their antiviral activity, cell toxicity and selectivity in dose response experiments. The screen at the lower concentration yielded three compounds, which displayed moderate activity (SI(50) = 10-49). Intriguingly, the screen at the higher concentration revealed several additional hits. Two of these hits were highly active with an SI(50) > 50. Time of addition experiments revealed one compound that inhibited early and four other compounds that inhibited late in the virus life cycle; suggesting they affect entry and replication, respectively. The active compounds represent several different classes of molecules such as carboxanilides, 1-benzoyl-3-arylthioureas, sulfonamides and benzothiazinones, which have not been previously identified as having anti-viral/anti-influenza activity.",,"['Severson, William E.', 'McDowell, Michael', 'Ananthan, Subramaniam', 'Chung, Dong-Hoon', 'Rasmussen, Lynn', 'Sosa, Melinda I.', 'White, E. Lucile', 'Noah, James', 'Jonsson, Colleen B.']",,,,
,PMC,Isolation of human monoclonal antibodies by mammalian cell display,http://dx.doi.org/10.1073/pnas.0805942105,PMC2567231,,,"Due to their low immunogenicity in patients, humanized or fully human mAbs are becoming increasingly important for the treatment of a growing number of diseases, including cancer, infections, and immune disorders. Here, we describe a technology allowing for the rapid isolation of fully human mAbs. In contrast to previously described methods, B cells specific for an antigen of interest are directly isolated from peripheral blood mononuclear cells (PBMC) of human donors. Recombinant, antigen-specific single-chain Fv (scFv) libraries are generated from this pool of B cells and screened by mammalian cell surface display by using a Sindbis virus expression system. This method allows isolating antigen-specific antibodies by a single round of FACS. The variable regions (VRs) of the heavy chains (HCs) and light chains (LCs) are isolated from positive clones and recombinant fully human antibodies produced as whole IgG or Fab fragments. In this manner, several hypermutated high-affinity antibodies binding the Qβ virus like particle (VLP), a model viral antigen, as well as antibodies specific for nicotine were isolated. All antibodies showed high expression levels in cell culture. The human nicotine-specific mAbs were validated preclinically in a mouse model. Thus, the technology presented here allows for rapid isolation of high-affinity, fully human antibodies with therapeutic potential from human volunteers.",,"['Beerli, Roger R.', 'Bauer, Monika', 'Buser, Regula B.', 'Gwerder, Myriam', 'Muntwiler, Simone', 'Maurer, Patrik', 'Saudan, Philippe', 'Bachmann, Martin F.']",,,,
,PMC,Comparison of multiple vaccine vectors in a single heterologous prime boost trial,http://dx.doi.org/10.1016/j.vaccine.2008.09.007,PMC2646904,,,"The prevention of infectious disease via prophylactic immunization is a mainstay of global public health efforts. Vaccine design would be facilitated by a better understanding of the type and durability of immune responses generated by different vaccine vectors. We report here the results of a comparative immunogenicity trial of six different vaccine vectors expressing the same insert antigen, cowpox virus B5 (CPXV-B5). Of those vectors tested, recombinant adenovirus (rAd5) was the most immunogenic, inducing the highest titer anti-B5 antibodies and conferring protection from sublethal vaccinia virus challenge in mice after a single immunization. We tested select heterologous prime-boost combinations and identified recombinant vesicular stomatitis virus (rVSV) and recombinant Venezuelan equine encephalitis virus replicons (VRP) as the most synergistic regimen. Comparative data such as those presented here are critical to efforts to generate protective vaccines for emerging infectious diseases as well as for biothreat agents.",,"['Barefoot, Brice', 'Thornburg, Natalie J.', 'Barouch, Daniel H.', 'Yu, Jae-sung', 'Sample, Christopher', 'Johnston, Robert E.', 'Liao, Hua Xin', 'Kepler, Thomas B.', 'Haynes, Barton F.', 'Ramsburg, Elizabeth']",,,,
,PMC,Utilization of DC-SIGN for Entry of Feline Coronaviruses into Host Cells,http://dx.doi.org/10.1128/JVI.01094-08,PMC2583691,,,"The entry and dissemination of viruses in several families can be mediated by C-type lectins such as DC-SIGN. We showed that entry of the serotype II feline coronavirus strains feline infectious peritonitis virus (FIPV) WSU 79-1146 and DF2 into nonpermissive mouse 3T3 cells can be rescued by the expression of human DC-SIGN (hDC-SIGN) and that infection of a permissive feline cell line (Crandall-Reese feline kidney) was markedly enhanced by the overexpression of hDC-SIGN. Treatment with mannan considerably reduced infection of feline monocyte-derived cells expressing DC-SIGN, indicating a role for FIPV infection in vivo.",,"['Regan, Andrew D.', 'Whittaker, Gary R.']",,,,
,PMC,Clinical and laboratory features that distinguish dengue from other febrile illnesses in endemic populations,http://dx.doi.org/10.1111/j.1365-3156.2008.02151.x,PMC2756447,,,"OBJECTIVE: Clinicians in resource-poor countries need to identify patients with dengue using readily-available data. The objective of this systematic review was to identify clinical and laboratory features that differentiate dengue fever (DF) and/or dengue hemorrhagic fever (DHF) from other febrile illnesses (OFI) in dengue-endemic populations. METHODS: Systematic review of the literature from 1990-Oct. 30, 2007 including English publications comparing dengue and OFI. RESULTS: Among 49 studies reviewed, 34 did not meet our criteria for inclusion. Of the 15 studies included, 10 were prospective cohort studies and five were case-control studies. Seven studies assessed all ages, four assessed children only, and four assessed adults only. Patients with dengue had significantly lower platelet, white blood cell (WBC) and neutrophil counts, and a higher frequency of petechiae than OFI patients. Higher frequencies of myalgia, rash, hemorrhagic signs, lethargy/prostration, and arthralgia/joint pain and higher hematocrits were reported in adult patients with dengue but not in children. Most multivariable models included platelet count, WBC, rash, and signs of liver damage; however, none had high statistical validity and none considered changes in clinical features over the course of illness. CONCLUSIONS: Several individual clinical and laboratory variables distinguish dengue from OFI; however, some variables may be dependent on age. No published multivariable model has been validated. Study design, populations, diagnostic criteria, and data collection methods differed widely across studies, and the majority of studies did not identify specific etiologies of OFIs. More prospective studies are needed to construct a valid and generalizable algorithm to guide the differential diagnosis of dengue in endemic countries.",,"['Potts, James A.', 'Rothman, Alan L.']",,,,
,PMC,Molecular targets for flavivirus drug discovery,http://dx.doi.org/10.1016/j.antiviral.2008.08.004,PMC2647018,,,"Flaviviruses are a major cause of infectious disease in humans. Dengue virus causes an estimated 50 million cases of febrile illness each year, including an increasing number of cases of hemorrhagic fever. West Nile virus, which recently spread from the Mediterranean basin to the Western Hemisphere, now causes thousands of sporadic cases of encephalitis annually. Despite the existence of licensed vaccines, yellow fever, Japanese encephalitis and tick-borne encephalitis also claim many thousands of victims each year across their vast endemic areas. Antiviral therapy could potentially reduce morbidity and mortality from flavivirus infections, but no effective drugs are currently available. This article introduces a collection of papers in Antiviral Research on molecular targets for flavivirus antiviral drug design and murine models of dengue virus disease that aims to encourage drug development efforts. After reviewing the flavivirus replication cycle, we discuss the envelope glycoprotein, NS3 protease, NS3 helicase, NS5 methyltransferase and NS5 RNA-dependent RNA polymerase as potential drug targets, with special attention being given to the viral protease. The other viral proteins are the subject of individual articles in the journal. Together, these papers highlight current status of drug discovery efforts for flavivirus diseases and suggest promising areas for further research.",,"['Sampath, Aruna', 'Padmanabhan, R.']",,,,
,PMC,Human Metapneumovirus Reinfection among Children in Thailand Determined by an Enzyme-Linked Immunosorbent Assay Using Purified Soluble Fusion Protein,http://dx.doi.org/10.1086/591186,PMC2648801,,,"BACKGROUND: Human metapneumovirus (hMPV) is a newly discovered paramyxovirus that causes acute respiratory illness. Despite apparent near-universal exposure during early childhood, immunity is transient. METHODS: An indirect screening ELISA using a recombinant, soluble, fusion (F) glycoprotein derived from hMPV was used to test for anti-F IgG in 1,380 acute and convalescent sera collected from children in Kamphaeng Phet, Thailand RESULTS: 1,376 (99.7%) tested sera showed evidence of prior infection with hMPV. 67 children demonstrated a four-fold or greater rise in titer for an overall re-infection rate of 4.9%. Two children demonstrated evidence of an initial infection. 49 of the 69 new or re-infections occurred in 2000, accounting for 13.2% of all non-flaviviral febrile illnesses in the study population in that year. Of 69 positive cases, 89.9% reported a respiratory symptom compared to 69.2% of tested negative cases (p<.001). All positive specimens were also tested for an increase in titer to RSV F and 27% exhibited a four-fold or greater rise in titer. CONCLUSION: These results demonstrate hMPV reinfection causing illness at rates equal to that seen for initial infections. hMPV may represent a more significant impact in older children than previously realized and may be the cause of significant outbreaks.",,"['Pavlin, Julie A.', 'Hickey, Andrew C.', 'Ulbrandt, Nancy', 'Chan, Yee-Peng', 'Endy, Timothy P.', 'Boukhvalova, Marina S.', 'Chunsuttiwat, Supamit', 'Nisalak, Ananda', 'Libraty, Daniel H.', 'Green, Sharone', 'Rothman, Alan L.', 'Ennis, Francis A.', 'Jarman, Richard', 'Gibbons, Robert V.', 'Broder, Christopher C.']",,,,
,PMC,Alcohol Abuse/Dependence Symptoms Among Hospital Employees Exposed to a SARS Outbreak,http://dx.doi.org/10.1093/alcalc/agn073,PMC2720767,,,"Aims: The aim of this study was to examine alcohol abuse/dependence symptoms among hospital employees exposed to a severe acute respiratory syndrome (SARS) outbreak, and the relationship between types of exposure to the SARS outbreak and subsequent alcohol abuse/dependence symptoms. Methods: A survey was conducted among 549 randomly selected hospital employees in Beijing, China, concerning the psychological impact of the 2003 SARS outbreak. Subjects were assessed on sociodemographic factors and types of exposure to the outbreak, and on symptoms of post-traumatic stress (PTS), alcohol abuse/dependence and depression. Results: Current alcohol abuse/dependence symptom counts 3 years after the outbreak were positively associated with having been quarantined, or worked in high-risk locations such as SARS wards, during the outbreak. However, having had family members or friends contract, SARS was not related to alcohol abuse/dependence symptom count. Symptoms of PTS and of depression, and having used drinking as a coping method, were also significantly associated with increased alcohol abuse/dependence symptoms. The relationship between outbreak exposure and alcohol abuse/dependence symptom count remained significant even when sociodemographic and other factors were controlled for. When the intrusion, avoidance and hyperarousal PTS symptom clusters were entered into the model, hyperarousal was found to be significantly associated with alcohol abuse/dependence symptoms. Conclusions: Exposure to an outbreak of a severe infectious disease can, like other disaster exposures, lead not only to PTSD but also to other psychiatric conditions, such as alcohol abuse/dependence. The findings will help policy makers and health professionals to better prepare for potential outbreaks of diseases such as SARS or avian flu.",,"['Wu, Ping', 'Liu, Xinhua', 'Fang, Yunyun', 'Fan, Bin', 'Fuller, Cordelia J.', 'Guan, Zhiqiang', 'Yao, Zhongling', 'Kong, Junhui', 'Lu, Jin', 'Litvak, Iva J.']",,,,
,PMC,A shifty stop for a hairy tail,http://dx.doi.org/10.1111/j.1365-2958.2008.06434.x,PMC2779026,,,"The tail apparatus of the bacteriophage SPP1 is an extraordinary ~1600-Å-long molecular machine. The tail mediates attachment of the virus to the host surface receptor, as well-as ejection of the viral genome into the host. The distal tip of the tail binds the extracellular ectodomain of the Bacillus subtilis receptor YueB, while the tail tube provides a conduit to funnel the viral genome into the host. This process, which culminates with the ejection of the ~44 kb of viral DNA across the thick, cell envelope of the Gram-positive bacterial cell, takes place in a time scale of seconds to minutes and represents a remarkable example of biotransformation. In this issue of Molecular Microbiology, Auzat et al. provide compelling evidence that the two major structural proteins of the SPP1 tail, gp17.1 (~19.1 kDa) and gp17.1* (~28 kDa), share a common N-terminal sequence, and that gp17.1* is generated by a translational frameshift in the gene 17.1. The extra domain fused to gp17.1* is synthesized by a +1 programmed translational frame-shift at the end of gene 17.1, which leads to the synthesis of approximately one gp17.1* for every three equivalents of gp17.1. This finding extends our current knowledge of translational frameshifts and provides a framework to understand how Siphoviridae phages like SPP1 have developed long-tail machines using only two major structural proteins.",,"['Olia, Adam S.', 'Cingolani, Gino']",,,,
,PMC,Respiratory Muscle Strength Predicts Decline in Mobility in Older Persons,http://dx.doi.org/10.1159/000154930,PMC2741394,,,"OBJECTIVES: To test the hypothesis that respiratory muscle strength is associated with the rate of change in mobility even after controlling for leg strength and physical activity. METHODS: Prospective study of 890 ambulatory older persons without dementia who underwent annual clinical evaluations to examine change in the rate of mobility over time. RESULTS: In a linear mixed-effect model adjusted for age, sex, and education, mobility declined about 0.12 unit/year, and higher levels of respiratory muscle strength were associated with a slower rate of mobility decline (estimate 0.043, SE 0.012, p < 0.001). Respiratory muscle strength remained associated with the rate of change in mobility even after controlling for lower extremity strength (estimate 0.036, SE 0.012, p = 0.004). In a model that included terms for respiratory muscle strength, lower extremity strength and physical activity together, all three were independent predictors of mobility decline in older persons. These associations remained significant even after controlling for body composition, global cognition, the development of dementia, parkinsonian signs, possible pulmonary disease, smoking, joint pain and chronic diseases. CONCLUSION: Respiratory muscle strength is associated with mobility decline in older persons independent of lower extremity strength and physical activity. Clinical interventions to improve respiratory muscle strength may decrease the burden of mobility impairment in the elderly.",,"['Buchman, A.S.', 'Boyle, P.A.', 'Wilson, R.S.', 'Leurgans, S.', 'Shah, R.C.', 'Bennett, D.A.']",,,,
,PMC,The Challenge of Respiratory Virus Infections in Hematopoietic Cell Transplant Recipients,http://dx.doi.org/10.1111/j.1365-2141.2008.07295.x,PMC2735199,,,"Respiratory virus infections in hematopoietic cell transplant (HCT) recipients are a major cause of morbidity and mortality. While respiratory syncytial virus (RSV), human metapneumonvirus, parainfluenzaviruses, and influenza viruses are well known for their potential to cause fatal pneumonia, information is emerging only recently on the significance of the newly discovered viruses such as human coronaviruses NL63 and HKU1, and human bocavirus. Lymphopenia seems to be the most recent risk factors for progression to lower respiratory tract disease. Airflow obstruction is another complication of respiratory virus infections after HCT, and data to date indicate this complication may occur following parainfluenza virus and RSV infection. Infection control procedures are key for prevention. Unfortunately, there are no randomized treatment studies, which make the interpretation of the literature on interventions difficult. This article reviews the spectrum of pathogens, epidemiology, risk factors and clinical manifestations of infection, as well as recent advances in diagnostic and clinical management.",,"Boeckh, Michael",,,,
,PMC,Entry from the Cell Surface of Severe Acute Respiratory Syndrome Coronavirus with Cleaved S Protein as Revealed by Pseudotype Virus Bearing Cleaved S Protein,http://dx.doi.org/10.1128/JVI.01412-08,PMC2583654,,,"Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is known to take an endosomal pathway for cell entry; however, it is thought to enter directly from the cell surface when a receptor-bound virion spike (S) protein is affected by trypsin, which induces cleavage of the S protein and activates its fusion potential. This suggests that SARS-CoV bearing a cleaved form of the S protein can enter cells directly from the cell surface without trypsin treatment. To explore this possibility, we introduced a furin-like cleavage sequence in the S protein at amino acids 798 to 801 and found that the mutated S protein was cleaved and induced cell fusion without trypsin treatment when expressed on the cell surface. Furthermore, a pseudotype virus bearing a cleaved S protein was revealed to infect cells in the presence of a lysosomotropic agent as well as a protease inhibitor, both of which are known to block SARS-CoV infection via an endosome, whereas the infection of pseudotypes with an uncleaved, wild-type S protein was blocked by these agents. A heptad repeat peptide, derived from a SARS-CoV S protein that is known to efficiently block infections from the cell surface, blocked the infection by a pseudotype with a cleaved S protein but not that with an uncleaved S protein. Those results indicate that SARS-CoV with a cleaved S protein is able to enter cells directly from the cell surface and agree with the previous observation of the protease-mediated cell surface entry of SARS-CoV.",,"['Watanabe, Rie', 'Matsuyama, Shutoku', 'Shirato, Kazuya', 'Maejima, Masami', 'Fukushi, Shuetsu', 'Morikawa, Shigeru', 'Taguchi, Fumihiro']",,,,
,PMC,Applications of protein microarrays for biomarker discovery,http://dx.doi.org/10.1002/prca.200800032,PMC3158026,,,"The search for new biomarkers for diagnosis, prognosis and therapeutic monitoring of diseases continues in earnest despite dwindling success at finding novel reliable markers. Some of the current markers in clinical use do not provide optimal sensitivity and specificity, with the prostate cancer antigen (PSA) being one of many such examples. The emergence of proteomic techniques and systems approaches to study disease pathophysiology has rekindled the quest for new biomarkers. In particular the use of protein microarrays has surged as a powerful tool for large scale testing of biological samples. Approximately half the reports on protein microarrays have been published in the last two years especially in the area of biomarker discovery. In this review, we will discuss the application of protein microarray technologies that offer unique opportunities to find novel biomarkers.",,"['Ramachandran, Niroshan', 'Srivastava, Sanjeeva', 'LaBaer, Joshua']",,,,
,PMC,Multiple viral respiratory pathogens in children with bronchiolitis,http://dx.doi.org/10.1111/j.1651-2227.2008.01023.x,PMC2605206,,,"AIM: The aim of the study was to describe the frequency of viral pathogens and relative frequency of co-infections in nasal specimens obtained from young children with bronchiolitis receiving care at a children’s hospital. METHODS: We conducted a study of nasal wash specimens using real-time PCR and fluorescent-antibody assay results from children less than two with an ICD-9-CM code for bronchiolitis. All specimens were collected for clinical care at Children’s Hospital in Seattle, WA, USA, during the respiratory season from October 2003 to April 2004. RESULTS: Viruses were detected in 168 (93%) of the 180 children with bronchiolitis. A single virus was identified in 127 (71%) children and multiple viruses in 41 (23%). Respiratory syncytial virus (RSV) was the most common virus detected (77%), followed by adenovirus (15%), human metapneumovirus (11%), coronavirus (8%), parainfluenza (6%) and influenza (1%). Of the 139 samples with RSV detected, 34 (24%) were co-infected with another viral pathogen. CONCLUSION: Molecular diagnostic techniques identified a high frequency of viruses and viral co-infections among children evaluated for bronchiolitis. Further study of the role of viral pathogens other than RSV and co-infections with RSV in children with bronchiolitis appears warranted.",,"['Stempel, Hilary E', 'Martin, Emily T', 'Kuypers, Jane', 'Englund, Janet A', 'Zerr, Danielle M']",,,,
,PMC,Inhibition of norovirus replication by morpholino oligomers targeting the 5′-end of the genome,http://dx.doi.org/10.1016/j.virol.2008.08.007,PMC3703767,,,"Noroviruses are an important cause of non-bacterial epidemic gastroenteritis, but no specific antiviral therapies are available. We investigated the inhibitory effect of phosphorodiamidiate morpholino oligomers (PMOs) targeted against norovirus sequences. A panel of peptide-conjugated PMOs (PPMOs) specific for the murine norovirus (MNV) genome was developed, and two PPMO compounds directed against the first AUG of the ORF1 coding sequence near the 5′-end of the genome proved effective in inhibiting MNV replication in cells. A consensus PPMO (designated Noro 1.1), designed to target the corresponding region of several diverse human norovirus genotypes, decreased the efficiency of protein translation in a cell-free luciferase reporter assay and inhibited Norwalk virus protein expression in replicon-bearing cells. Our data suggest that PPMOs directed against the relatively conserved 5′-end of the norovirus genome may show broad antiviral activity against this genetically diverse group of viruses.",,"['Bok, Karin', 'Cavanaugh, Victoria J.', 'Matson, David O.', 'González-Molleda, Lorenzo', 'Chang, Kyeong-Ok', 'Zintz, Carmelann', 'Smith, Alvin W.', 'Iversen, Patrick', 'Green, Kim Y.', 'Campbell, Ann E.']",,,,
,PMC,Positional cloning of the Igl genes controlling rheumatoid factor production and allergic bronchitis in rats,http://dx.doi.org/10.1073/pnas.0803956105,PMC2544569,,,"Rheumatoid factors (RF), autoantibodies that bind the Fc region of IgG, are one of the major diagnostic marker in rheumatoid arthritis (RA) but occur with lower frequency also in other infectious and inflammatory conditions. Through positional cloning of the previously described quantitative trait locus (QTL) Rf1 in congenic and advanced intercrossed rats, we identified the Ig lambda light chain locus as a locus that regulates the production of RF in rats. The congenic rats produce RF-Igλ and have significant higher levels of RF-IgG and RF-IgM in serum, while the DA rat has an impaired RF production and does not produces RF-Igλ. Thus, we could investigate the role of RF in pristane-induced arthritis (PIA) as well as ovalbumin-induced airway inflammation. We show that there was no difference in the development and severity of PIA between congenic and parental DA rats, suggesting that RF using lambda light chains have no impact on PIA. However, the RF producing congenic rats developed a more severe airway inflammation as indicated in the significantly increased number of eosinophils in bronchoalveolar lavage fluid as well as total IgE in serum. In addition, RF congenic rats had a significantly enhanced immune response toward OVA due to increased OVA-Igk but not OVA-Igl antibodies, suggesting a possible involvement of RF in the regulation of the humoral immune response.",,"['Rintisch, Carola', 'Ameri, Jacqueline', 'Olofsson, Peter', 'Luthman, Holger', 'Holmdahl, Rikard']",,,,
,PMC,"Licorice β-amyrin 11-oxidase, a cytochrome P450 with a key role in the biosynthesis of the triterpene sweetener glycyrrhizin",http://dx.doi.org/10.1073/pnas.0803876105,PMC2532699,,,"Glycyrrhizin, a major bioactive compound derived from the underground parts of Glycyrrhiza (licorice) plants, is a triterpene saponin that possesses a wide range of pharmacological properties and is used worldwide as a natural sweetener. Because of its economic value, the biosynthesis of glycyrrhizin has received considerable attention. Glycyrrhizin is most likely derived from the triterpene β-amyrin, an initial product of the cyclization of 2,3-oxidosqualene. The subsequent steps in glycyrrhizin biosynthesis are believed to involve a series of oxidative reactions at the C-11 and C-30 positions, followed by glycosyl transfers to the C-3 hydroxyl group; however, no genes encoding relevant oxidases or glycosyltransferases have been identified. Here we report the successful identification of CYP88D6, a cytochrome P450 monooxygenase (P450) gene, as a glycyrrhizin-biosynthetic gene, by transcript profiling-based selection from a collection of licorice expressed sequence tags (ESTs). CYP88D6 was characterized by in vitro enzymatic activity assays and shown to catalyze the sequential two-step oxidation of β-amyrin at C-11 to produce 11-oxo-β-amyrin, a possible biosynthetic intermediate between β-amyrin and glycyrrhizin. CYP88D6 coexpressed with β-amyrin synthase in yeast also catalyzed in vivo oxidation of β-amyrin to 11-oxo-β-amyrin. CYP88D6 expression was detected in the roots and stolons by RT-PCR; however, no amplification was observed in the leaves or stems, which is consistent with the accumulation pattern of glycyrrhizin in planta. These results suggest a role for CYP88D6 as a β-amyrin 11-oxidase in the glycyrrhizin pathway.",,"['Seki, Hikaru', 'Ohyama, Kiyoshi', 'Sawai, Satoru', 'Mizutani, Masaharu', 'Ohnishi, Toshiyuki', 'Sudo, Hiroshi', 'Akashi, Tomoyoshi', 'Aoki, Toshio', 'Saito, Kazuki', 'Muranaka, Toshiya']",,,,
,PMC,Reverse genetics approaches to combat pathogenic arenaviruses,http://dx.doi.org/10.1016/j.antiviral.2008.08.002,PMC2628465,,,"Several arenaviruses cause hemorrhagic fever (HF) in humans, and evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance. Moreover, arenaviruses pose a biodefense threat. No licensed anti-arenavirus vaccines are available, and current anti-arenavirus therapy is limited to the use of ribavirin, which is only partially effective and is associated with anemia and other side effects. Therefore, it is important to develop effective vaccines and better antiviral drugs to combat the dual threats of naturally occurring and intentionally introduced arenavirus infections. The development of arenavirus reverse genetic systems is allowing investigators to conduct a detailed molecular characterization of the viral cis-acting signals and trans-acting factors that control each of the steps of the arenavirus life cycle, including RNA synthesis, packaging and budding. Knowledge derived from these studies is uncovering potential novel targets for therapeutic intervention, as well as facilitating the establishment of assays to identify and characterize candidate antiviral drugs capable of interfering with specific steps of the virus life cycle. Likewise, the ability to generate predetermined specific mutations within the arenavirus genome and analyze their phenotypic expression would significantly contribute to the elucidation of arenavirus-host interactions, including the basis of their ability to cause severe HF. This, in turn, could lead to the development of novel, potent and safe arenavirus vaccines.",,"de la Torre, Juan C.",,,,
,PMC,Eating the enemy within: autophagy in infectious diseases,http://dx.doi.org/10.1038/cdd.2008.130,PMC2736877,,,"Autophagy is emerging as a central component of antimicrobial host defense against diverse viral, bacterial, and parasitic infections. In addition to pathogen degradation, autophagy has other functions during infection such as innate and adaptive immune activation. As an important host defense pathway, microbes have also evolved mechanisms to evade, subvert, or exploit autophagy. Additionally, some fungal pathogens harness autophagy within their own cells to promote pathogenesis. This review will highlight our current understanding of autophagy in infection, focusing on the most recent advances in the field, and will discuss the potential implications of these studies in the design of anti-infective therapeutics.",,"['Orvedahl, A', 'Levine, B']",,,,
,PMC,Identification of cardioviruses related to Theiler's murine encephalomyelitis virus in human infections,http://dx.doi.org/10.1073/pnas.0805968105,PMC2528868,,,"Cardioviruses comprise a genus of picornaviruses that cause severe illnesses in rodents, but little is known about the prevalence, diversity, or spectrum of disease of such agents among humans. A single cardiovirus isolate, Saffold virus, was cultured in 1981 in stool from an infant with fever. Here, we describe the identification of a group of human cardioviruses that have been cloned directly from patient specimens, the first of which was detected using a pan-viral microarray in respiratory secretions from a child with influenza-like illness. Phylogenetic analysis of the nearly complete viral genome (7961 bp) revealed that this virus belongs to the Theiler's murine encephalomyelitis virus (TMEV) subgroup of cardioviruses and is most closely related to Saffold virus. Subsequent screening by RT-PCR of 719 additional respiratory specimens [637 (89%) from patients with acute respiratory illness] and 400 cerebrospinal fluid specimens from patients with neurological disease (aseptic meningitis, encephalitis, and multiple sclerosis) revealed no evidence of cardiovirus infection. However, screening of 751 stool specimens from 498 individuals in a gastroenteritis cohort resulted in the detection of 6 additional cardioviruses (1.2%). Although all 8 human cardioviruses (including Saffold virus) clustered together by phylogenetic analysis, significant sequence diversity was observed in the VP1 gene (66.9%–100% pairwise amino acid identities). These findings suggest that there exists a diverse group of novel human Theiler's murine encephalomyelitis virus-like cardioviruses that hitherto have gone largely undetected, are found primarily in the gastrointestinal tract, can be shed asymptomatically, and have potential links to enteric and extraintestinal disease.",,"['Chiu, Charles Y.', 'Greninger, Alexander L.', 'Kanada, Kimberly', 'Kwok, Thomas', 'Fischer, Kael F.', 'Runckel, Charles', 'Louie, Janice K.', 'Glaser, Carol A.', 'Yagi, Shigeo', 'Schnurr, David P.', 'Haggerty, Tom D.', 'Parsonnet, Julie', 'Ganem, Don', 'DeRisi, Joseph L.']",,,,
,PMC,SHEA/APIC Guideline: Infection Prevention and Control in the Long-Term Care Facility,http://dx.doi.org/10.1016/j.ajic.2008.06.001,PMC3375028,,,,,"['Smith, Philip W.', 'Bennett, Gail', 'Bradley, Suzanne', 'Drinka, Paul', 'Lautenbach, Ebbing', 'Marx, James', 'Mody, Lona', 'Nicolle, Lindsay', 'Stevenson, Kurt']",,,,
,PMC,Public Health Education and the World,http://dx.doi.org/10.2105/AJPH.2008.144758,PMC2509602,,,,,"Yu, Stella M.",,,,
,PMC,A Decentralized Molecular Diagnostic Testing Plan for Pandemic Influenza in the Ontario Public Health Laboratory System,http://dx.doi.org/10.1007/BF03405247,PMC6975982,,,"The Ontario Public Health Laboratories system (OPHL) is in the midst of a six-year plan to implement molecular tools for pandemic influenza diagnostics in one central and three regional public health laboratories. This plan has been formulated as a consequence of: 1) experiences gained through severe acute respiratory syndrome (SARS), and comments of the members of the Expert Panel on SARS and Infectious Disease Control (i.e., the Walker report); 2) a review of pandemic preparedness literature; 3) historical and epidemiologic discussions about previous pandemics; and 4) suggestions made by various pandemic working committees. The OPHL plan includes: 1) an aggressive restructuring of the overall molecular microbiology testing capacity of the OPHL; 2) the ability to shift influenza testing of samples between designated OPHL laboratories; and 3) the development of screening tools for pandemic influenza diagnostic tests. The authors believe that investing in increased molecular testing capacity for regional laboratories outside the greater Toronto area will be beneficial to the OPHL system whether or not an influenza pandemic occurs. Well-trained technologists and microbiologists, and the introduction of new technologies, will facilitate the development of a wide variety of molecular tests for other infectious diseases at public health laboratories geographically distant from Toronto, thus enhancing overall laboratory testing capacity in the province of Ontario.",,"['Drews, Steven J.', 'Majury, Anna', 'Jamieson, Frances', 'Riley, Garth', 'Mazzulli, Tony', 'Low, Donald E.']",,,,
,PMC,Concise Definitive Review: Influenza,http://dx.doi.org/10.1097/CCM.0b013e318180b039,PMC3431208,,,,,"Beigel, John H.",,,,
,PMC,SHEA/APIC Guideline: Infection Prevention and Control in the Long-Term Care Facility,http://dx.doi.org/10.1086/592416,PMC3319407,,,,,"['Smith, Philip W.', 'Bennett, Gail', 'Bradley, Suzanne', 'Drinka, Paul', 'Lautenbach, Ebbing', 'Marx, James', 'Mody, Lona', 'Nicolle, Lindsay', 'Stevenson, Kurt']",,,,
,PMC,A technological update of molecular diagnostics for infectious diseases,,PMC2567840,,,"Identification of a causative pathogen is essential for the choice of treatment for most infectious diseases. Many FDA approved molecular assays; usually more sensitive and specific compared to traditional tests, have been developed in the last decade. A new trend of high throughput and multiplexing assays are emerging thanks to technological developments for the human genome sequencing project. The applications of microarray and ultra high throughput sequencing technologies for diagnostic microbiology are reviewed. The race for the $1000 genome technology by 2014 will have a profound impact in diagnosis and treatment of infectious diseases in the near future.",,"Liu, Yu-Tsueng",,,,
,PMC,"Retrospective Clinical and Molecular Analysis of Conditioned Laboratory Dogs (Canis familiaris) with Serologic Reactions to Ehrlichia canis, Borrelia burgdorferi, and Rickettsia rickettsii",,PMC2691535,,,"Dogs are susceptible to different tickborne infections, including members of the Anaplasmataceae (Ehrlichia canis, E. ewingii, E. chaffeensis, Anaplasma phagocytophilum, A. platys), Borrelia burgdorferi, and Rickettsia rickettsii. These diseases can manifest with clinical signs including fever, anorexia, malaise, lameness, rash, and bleeding episodes; however, these signs are nonpathognomonic, and infections can occur in the absence of clinical signs. Hematologic abnormalities can include leukopenia, thrombocytopenia, hyperproteinemia and hypergammaglobulinemia. In biomedical research, diseases such as canine monocytic ehrlichiosis, Lyme disease, and Rocky Mountain spotted fever may cause morbidity among exposed dogs and confound research results. Random-source dogs are susceptible to these diseases because of their increased risk of arthropod exposure. Nonpurpose bred, randomly selected conditioned dogs (n = 21) were examined; blood samples were taken for hematology, biochemistry analysis, tickborne pathogen serology, and PCR. Of these, 2 dogs (10% of the population) presented with illness characterized by fever, malaise, lameness, or hemostatic abnormalities, and 15 (71%) had antibodies to one or more tickborne pathogens. No specific hematologic or biochemical differences were apparent between seronegative dogs and seropositive dogs reactive to all 3 pathogens. E. canis and B. burgdorferi PCR of tissues and blood were negative for all dogs. PCR amplification of several Ehrlichia and Anaplasma genes yielded no positive samples. From this cohort of dogs, serologic and molecular results indicate prior exposure without active infection or clinical disease. Exposure to and potential for infection with these bacteria and other pathogens may contribute to blood and tissue alterations that could confound experiments and lead to misinterpretation of data in canine models.",,"['Scorpio, Diana G', 'Wachtman, Lynn M', 'Tunin, Richard S', 'Barat, Nicole C', 'Garyu, Justin W', 'Dumler, J Stephen']",,,,
,PMC,Development and Application of a Framework for Maintenance of Medical Terminological Systems,http://dx.doi.org/10.1197/jamia.M2531,PMC2528044,,,"OBJECTIVE: Terminological Systems (TSs) need to be maintained in order to sustain their utility. This paper describes a study aiming at the standardization of the maintenance processes of medical TSs by capturing the criteria for the management of the maintenance processes into a framework. Furthermore, this paper describes application of the framework, which sheds light on the current practice of TS maintenance. DESIGN: Observational study. MEASUREMENTS: By means of a literature study, criteria for the maintenance of TSs were obtained and categorized into a framework. The current practice of TS maintenance was explored by a survey among organizations that maintain a TS. Results were stratified by the size of the TS being maintained. RESULTS: From Sixty-three relevant articles, criteria for the maintenance processes of TSs were extracted and organized into four components. The primary component “Execution” concerns the core activities of the maintenance process. The other three components “Process management,” “Change specifications,” and “Editing tools” support the core activities of the component “Execution.” The survey had a response rate of 40% (37 of 93). The answers reflect the large variation in the number of criteria that are satisfied for the participating organizations. Overall, maintenance of larger TSs seems to satisfy more criteria. CONCLUSIONS: The framework is an important step towards standardization of the maintenance of medical TSs and can be used to eliminate shortcomings in this process. Surveying the current practice showed that there is ample room to improve the maintenance processes of medical TSs, especially for the smaller TSs.",,"['Bakhshi-Raiez, Ferishta', 'Cornet, Ronald', 'de Keizer, Nicolette F.']",,,,
,PMC,HOW LONG WILL MY MOUSE LIVE? MACHINE LEARNING APPROACHES FOR PREDICTION OF MOUSE LIFESPAN,,PMC2693389,,,"Prediction of individual lifespan based upon characteristics evaluated at middle-age represents a challenging objective for aging research. In this study, we used machine learning algorithms to construct models that predict lifespan in a stock of genetically heterogeneous mice. Lifespan-prediction accuracy of 22 algorithms was evaluated using a cross-validation approach, in which models were trained and tested with distinct subsets of data. Using a combination of body weight and T-cell subset measures evaluated before two years of age, we show that the lifespan quartile to which an individual mouse belongs can be predicted with an accuracy of 35.3% (± 0.10%). This result provides a new benchmark for the development of lifespan-predictive models, but improvement can be expected through identification of new predictor variables and development of computational approaches. Future work in this direction can provide tools for aging research and will shed light on associations between phenotypic traits and longevity.",,"['Swindell, William R.', 'Harper, James M.', 'Miller, Richard A.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.01440-08,PMC2519643,,,,,,,,,
,PMC,Analysis of synonymous codon usage and evolution of begomoviruses,http://dx.doi.org/10.1631/jzus.B0820005,PMC2528880,,,"Begomoviruses are single-stranded DNA viruses and cause severe diseases in major crop plants worldwide. Based on current genome sequence analyses, we found that synonymous codon usage variations in the protein-coding genes of begomoviruses are mainly influenced by mutation bias. Base composition analysis suggested that the codon usage bias of AV1 and BV1 genes is significant and their expressions are high. Fourteen codons were determined as translational optimal ones according to the comparison of codon usage patterns between highly and lowly expressed genes. Interestingly the codon usages between begomoviruses from the Old and the New Worlds are apparently different, which supports the idea that the bipartite begomoviruses of the New World might originate from bipartite ones of the Old World, whereas the latter evolve from the Old World monopartite begomoviruses.",,"['Xu, Xiao-zhong', 'Liu, Qing-po', 'Fan, Long-jiang', 'Cui, Xiao-feng', 'Zhou, Xue-ping']",,,,
,PMC,Cross-Species Virus Transmission and the Emergence of New Epidemic Diseases,http://dx.doi.org/10.1128/MMBR.00004-08,PMC2546865,,,"Summary: Host range is a viral property reflecting natural hosts that are infected either as part of a principal transmission cycle or, less commonly, as “spillover” infections into alternative hosts. Rarely, viruses gain the ability to spread efficiently within a new host that was not previously exposed or susceptible. These transfers involve either increased exposure or the acquisition of variations that allow them to overcome barriers to infection of the new hosts. In these cases, devastating outbreaks can result. Steps involved in transfers of viruses to new hosts include contact between the virus and the host, infection of an initial individual leading to amplification and an outbreak, and the generation within the original or new host of viral variants that have the ability to spread efficiently between individuals in populations of the new host. Here we review what is known about host switching leading to viral emergence from known examples, considering the evolutionary mechanisms, virus-host interactions, host range barriers to infection, and processes that allow efficient host-to-host transmission in the new host population.",,"['Parrish, Colin R.', 'Holmes, Edward C.', 'Morens, David M.', 'Park, Eun-Chung', 'Burke, Donald S.', 'Calisher, Charles H.', 'Laughlin, Catherine A.', 'Saif, Linda J.', 'Daszak, Peter']",,,,
,PMC,Methods for Sampling of Airborne Viruses,http://dx.doi.org/10.1128/MMBR.00002-08,PMC2546863,,,"Summary: To better understand the underlying mechanisms of aerovirology, accurate sampling of airborne viruses is fundamental. The sampling instruments commonly used in aerobiology have also been used to recover viruses suspended in the air. We reviewed over 100 papers to evaluate the methods currently used for viral aerosol sampling. Differentiating infections caused by direct contact from those caused by airborne dissemination can be a very demanding task given the wide variety of sources of viral aerosols. While epidemiological data can help to determine the source of the contamination, direct data obtained from air samples can provide very useful information for risk assessment purposes. Many types of samplers have been used over the years, including liquid impingers, solid impactors, filters, electrostatic precipitators, and many others. The efficiencies of these samplers depend on a variety of environmental and methodological factors that can affect the integrity of the virus structure. The aerodynamic size distribution of the aerosol also has a direct effect on sampler efficiency. Viral aerosols can be studied under controlled laboratory conditions, using biological or nonbiological tracers and surrogate viruses, which are also discussed in this review. Lastly, general recommendations are made regarding future studies on the sampling of airborne viruses.",,"['Verreault, Daniel', 'Moineau, Sylvain', 'Duchaine, Caroline']",,,,
,PMC,Architects of Assembly: roles of Flaviviridae nonstructural proteins in virion morphogenesis,http://dx.doi.org/10.1038/nrmicro1928,PMC2764292,,,"Viruses of the Flaviviridae family, including hepatitis C, dengue, and bovine viral diarrhoea, are responsible for significant morbidity and mortality worldwide. Recent advances in understanding virion assembly have uncovered commonalities among distantly related members of this family. We discuss the emerging hypothesis that physical virion components are not alone in forming the infectious particle, but that nonstructural proteins are intimately involved in orchestrating morphogenesis. Pinpointing the roles of Flaviviridae proteins in virion production could reveal new avenues for antiviral therapeutics.",,"['Murray, Catherine L.', 'Jones, Christopher T.', 'Rice, Charles M.']",,,,
,PMC,A complex RNA motif defined by three discontinuous 5-nucleotide-long strands is essential for Flavivirus RNA replication,http://dx.doi.org/10.1261/rna.993608,PMC2525960,,,"Tertiary or higher-order RNA motifs that regulate replication of positive-strand RNA viruses are as yet poorly understood. Using Japanese encephalitis virus (JEV), we now show that a key element in JEV RNA replication is a complex RNA motif that includes a string of three discontinuous complementary sequences (TDCS). The TDCS consists of three 5-nt-long strands, the left (L) strand upstream of the translation initiator AUG adjacent to the 5′-end of the genome, and the middle (M) and right (R) strands corresponding to the base of the Flavivirus-conserved 3′ stem–loop structure near the 3′-end of the RNA. The three strands are arranged in an antiparallel configuration, with two sets of base-pairing interactions creating L-M and M-R duplexes. Disrupting either or both of these duplex regions of TDCS completely abolished RNA replication, whereas reconstructing both duplex regions, albeit with mutated sequences, fully restored RNA replication. Modeling of replication-competent genomes recovered from a large pool of pseudorevertants originating from six replication-incompetent TDCS mutants suggests that both duplex base-pairing potentials of TDCS are required for RNA replication. In all cases, acquisition of novel sequences within the 3′M-R duplex facilitated a long-range RNA–RNA interaction of its 3′M strand with either the authentic 5′L strand or its alternative (invariably located upstream of the 5′ initiator), thereby restoring replicability. We also found that a TDCS homolog is conserved in other flaviviruses. These data suggest that two duplex base-pairings defined by the TDCS play an essential regulatory role in a key step(s) of Flavivirus RNA replication.",,"['Song, Byung-Hak', 'Yun, Sang-Im', 'Choi, Yu-Jeong', 'Kim, Jeong-Min', 'Lee, Chan-Hee', 'Lee, Young-Min']",,,,
,PMC,Anticodon loop mutations perturb reading frame maintenance by the E site tRNA,http://dx.doi.org/10.1261/rna.1170008,PMC2525952,,,"The ribosomal E site helps hold the reading frame. Certain tRNA mutations affect translation, and anticodon loop mutations can be especially detrimental. We studied the effects of mutations saturating the anticodon loop of the amber suppressor tRNA, Su7, on the ability to help hold the reading frame when in the E site. We also tested three mutations in the anticodon stem, as well as a mutation in the D stem (the “Hirsh” mutation). We used the Escherichia coli RF2 programmed frameshift site to monitor frame maintenance. Most anticodon loop mutations increase frameshifting, possibly by decreasing codon:anticodon stability. However, it is likely that the A site is more sensitive to anticodon loop structure than is the E site. Unexpectedly, the Hirsh mutation also increases frameshifting from the E site. Other work shows that mutation may increase the ability of tRNA to react in the A site, possibly by facilitating conformational changes required for aminoacyl-tRNA selection. We suggest that this property may decrease its ability to bind to the E site. Finally, the absence of the ms(2)io(6)A nucleoside modifications at A37 does not decrease the ability of tRNA to help hold the reading frame from the E site. This was also unexpected because the absence of these modifications affects translational properties of tRNA in A and P sites. The absence of a negative effect in the E site further highlights the differences among the substrate requirements of the ribosomal coding sites.",,"['Sanders, Christina L.', 'Lohr, Kristin J.', 'Gambill, Holly L.', 'Curran, Ryan B.', 'Curran, James F.']",,,,
,PMC,"Design, Synthesis and Antiviral Efficacy of a Series of Potent Chloropyridyl Ester-derived SARS-CoV 3CLpro Inhibitors",http://dx.doi.org/10.1016/j.bmcl.2008.08.082,PMC2745596,,,"Design, synthesis and biological evaluation of a series of 5-chloropyridine ester-derived severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors is described. Position of the carboxylate functionality is critical to potency. Inhibitor 10 with a 5-chloropyridinyl ester at position 4 of the indole ring is the most potent inhibitor with a SARS 3Clpro IC(50) value of 30 nM and antiviral EC(50) value of 6.9 μM. Molecular Docking studies have provided possible binding modes of these inhibitors. [Image: see text]",,"['Ghosh, Arun K.', 'Gong, Gangli', 'Grum-Tokars, Valerie', 'Mulhearn, Debbie C.', 'Baker, Susan C.', 'Coughlin, Melissa', 'Prabhakar, Bellur S.', 'Sleeman, Katrina', 'Johnson, Michael E.', 'Mesecar, Andrew D.']",,,,
,PMC,An immunosuppressed Syrian golden hamster model for SARS-CoV infection,http://dx.doi.org/10.1016/j.virol.2008.07.026,PMC3722600,,,"Several small animal models have been developed for the study of severe acute respiratory syndrome coronavirus (SARS-CoV) replication and pathogenesis. Syrian golden hamsters are among the best small animal models, though little clinical illness and no mortality are observed after virus infection. Cyclophosphamide was used to immunosuppress hamsters leading to a prolonged disease course and higher mortality after SARS-CoV infection. In addition, there was a significant weight loss, expanded tissue tropism, and increased viral pathology in the lung, heart, kidney, and nasal turbinate tissues. Infection with recombinant SARS-CoV viruses bearing disruptions in the gene 7 coding region showed no significant change in replication kinetics, tissue tropism, morbidity, or mortality suggesting that the ORF7a (7a) and ORF7b (7b) proteins are not required for virus replication in immunosuppressed hamsters. This modified hamster model may provide a useful tool for SARS-CoV pathogenesis studies, evaluation of antiviral therapy, and analysis of additional SARS-CoV mutants.",,"['Schaecher, Scott R.', 'Stabenow, Jennifer', 'Oberle, Christina', 'Schriewer, Jill', 'Buller, R. Mark', 'Sagartz, John E.', 'Pekosz, Andrew']",,,,
,PMC,"The M, E, and N Structural Proteins of the Severe Acute Respiratory Syndrome Coronavirus Are Required for Efficient Assembly, Trafficking, and Release of Virus-Like Particles",http://dx.doi.org/10.1128/JVI.01052-08,PMC2573274,,,"The production of virus-like particles (VLPs) constitutes a relevant and safe model to study molecular determinants of virion egress. The minimal requirement for the assembly of VLPs for the coronavirus responsible for severe acute respiratory syndrome in humans (SARS-CoV) is still controversial. Recent studies have shown that SARS-CoV VLP formation depends on either M and E proteins or M and N proteins. Here we show that both E and N proteins must be coexpressed with M protein for the efficient production and release of VLPs by transfected Vero E6 cells. This suggests that the mechanism of SARS-CoV assembly differs from that of other studied coronaviruses, which only require M and E proteins for VLP formation. When coexpressed, the native envelope trimeric S glycoprotein is incorporated onto VLPs. Interestingly, when a fluorescent protein tag is added to the C-terminal end of N or S protein, but not M protein, the chimeric viral proteins can be assembled within VLPs and allow visualization of VLP production and trafficking in living cells by state-of-the-art imaging technologies. Fluorescent VLPs will be used further to investigate the role of cellular machineries during SARS-CoV egress.",,"['Siu, Y. L.', 'Teoh, K. T.', 'Lo, J.', 'Chan, C. M.', 'Kien, F.', 'Escriou, N.', 'Tsao, S. W.', 'Nicholls, J. M.', 'Altmeyer, R.', 'Peiris, J. S. M.', 'Bruzzone, R.', 'Nal, B.']",,,,
,PMC,Detection of Soluble Angiotensin-Converting Enzyme 2 in Heart Failure: Insights Into the Endogenous Counter-Regulatory Pathway of the Renin-Angiotensin-Aldosterone System,http://dx.doi.org/10.1016/j.jacc.2008.02.088,PMC2856943,,,"OBJECTIVES: We sought to determine whether circulating soluble angiotensin-converting enzyme 2 (sACE2) is increased in the plasma of patients with heart failure (HF). BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is an integral membrane protein that antagonizes the actions of angiotensin II and prevents the development of HF in animal models. However, because of the need for invasive cardiac tissue sampling, little is known about whether ACE2 is involved in the pathophysiology of HF in humans. METHODS: We developed a sensitive and specific assay to measure sACE2 activity in human plasma and screened a heterogeneous group of patients suspected of having clinical HF. RESULTS: Increasing sACE2 plasma activity strongly correlated with a clinical diagnosis of HF (p = 0.0002), worsening left ventricular ejection fraction (p < 0.0001), and increasing B-type natriuretic peptide levels (p < 0.0001). Similar to B-type natriuretic peptide, sACE2 activity reflected the severity of HF, with increasing levels associated with worsening New York Heart Association functional class (p < 0.0001). These associations were independent of other disease states and medication use. We found that sACE2 activity was increased in patients with both ischemic and nonischemic cardiomyopathies and also in patients with clinical HF but a preserved left ventricular ejection fraction. CONCLUSIONS: Soluble ACE2 activity is increased in patients with HF and correlates with disease severity, suggesting that a cardioprotective arm of the renin-angiotensin-aldosterone system is active in HF.",,"['Epelman, Slava', 'Tang, W. H. Wilson', 'Chen, Stephen Y.', 'Van Lente, Frederick', 'Francis, Gary S.', 'Sen, Subha']",,,,
,PMC,BEI Resources: Supporting antiviral research,http://dx.doi.org/10.1016/j.antiviral.2008.07.003,PMC2614313,,,"The Biodefense and Emerging Infections Research Resources Repository (BEI Resources) provides unique, quality-assured reagents to the scientific community for use in basic research and product development involving biodefense and emerging infectious diseases. These include microorganisms (up to Biosafety Level-3) on the National Institute of Allergy and Infectious Diseases (NIAID) and Centers for Disease Control and Prevention (CDC) lists of Category A, B and C priority pathogens. In addition to live microorganisms, related products such as polyclonal antisera, monoclonal antibodies, isolated nucleic acid preparations, overlapping peptide arrays, purified proteins, and assay kits are also available. Many of these materials have direct or indirect applications in antiviral research. These reagents are available free of charge to all registered investigators, regardless of funding source or affiliation. Acquisition of new reagents for the repository is one of the critically necessary and challenging tasks for BEI Resources. Therefore, investigators are encouraged to deposit relevant items, so as to provide access to materials, relief from the burden of distribution, protection of intellectual property rights, and secure storage. In addition, BEI Resources has the capability of contracting for the preparation of specific reagents. If there is a resource needed to advance a specific research area, contact an NIAID program officer or use the “suggest a reagent” option on the BEI Resources homepage, www.beiresources.org.",,"['Baker, Robert', 'Peacock, Susan']",,,,
,PMC,The ubiquitin-proteasome system in spongiform degenerative disorders,http://dx.doi.org/10.1016/j.bbadis.2008.08.006,PMC2612938,,,"Spongiform degeneration is characterized by vacuolation in nervous tissue accompanied by neuronal death and gliosis. Although spongiform degeneration is a hallmark of prion diseases, this pathology is also present in the brains of patients suffering from Alzheimer's disease, diffuse Lewy body disease, human immunodeficiency virus (HIV) infection, and Canavan's spongiform leukodystrophy. The shared outcome of spongiform degeneration in these diverse diseases suggests that common cellular mechanisms must underlie the processes of spongiform change and neurodegeneration in the central nervous system. Immunohistochemical analysis of brain tissues reveals increased ubiquitin immunoreactivity in and around areas of spongiform change, suggesting the involvement of ubiquitin-proteasome system dysfunction in the pathogenesis of spongiform neurodegeneration. The link between aberrant ubiquitination and spongiform neurodegeneration has been strengthened by the discovery that a null mutation in the E3 ubiquitin-protein ligase mahogunin ring finger-1 (Mgrn1) causes an autosomal recessively inherited form of spongiform neurodegeneration in animals. Recent studies have begun to suggest that abnormal ubiquitination may alter intracellular signaling and cell functions via proteasome-dependent and proteasome-independent mechanisms, leading to spongiform degeneration and neuronal cell death. Further elucidation of the pathogenic pathways involved in spongiform neurodegeneration should facilitate the development of novel rational therapies for treating prion diseases, HIV infection, and other spongiform degenerative disorders.",,"['Whatley, Brandi R.', 'Li, Lian', 'Chin, Lih-Shen']",,,,
,PMC,DOSE DEPENDENT LYMPHOCYTE APOPTOSIS FOLLOWING RESPIRATORY INFECTION WITH VACCINIA VIRUS,http://dx.doi.org/10.1016/j.virusres.2008.07.010,PMC2637442,,,"Recently there has been renewed interest in poxvirus pathogenesis, especially with regard to infection via the respiratory route. Members of this family are known to produce a number of proteins that have the potential to negatively regulate the immune response. Vaccinia virus (VACV) has been used for a number of years as a model for the study of poxvirus infection. We have previously reported a dose dependent decrease in virus-specific CD8(+) T cells following respiratory infection with VACV. In this study we have evaluated whether more generalized immunosuppressive effects are also observed following infection with a high dose of VACV. We have found that mice infected intranasally with a high, but non-lethal, dose of VACV exhibited significant weight loss as well as decreased thymocyte number. Although these mice mounted an immune response, there was a significant increase observed in bystander T and B cell apoptosis. While increased death was apparent in both naïve and activated/memory T cells populations, naive T cells appeared more sensitive to this effect. These findings are important for our understanding of poxvirus regulation of the immune response and extends our previous understanding of VACV mediated immunosuppression to include generalized apoptosis in the naïve and activated/memory repertoires.",,"['Yates, Nicole L.', 'Alexander-Miller, Martha A.']",,,,
,PMC,"Amicus or Adversary: Platelets in Lung Biology, Acute Injury, and Inflammation",http://dx.doi.org/10.1165/rcmb.2008-0241TR,PMC2633137,,,"Platelets are the chief effector cells in hemostasis and have additional major functions in inflammation, vascular integrity, and tissue repair. Platelets and the lungs have interrelated activities. Previous studies provide evidence that platelets contribute to pulmonary vascular barrier function and are required for defense against pulmonary hemorrhage, and that the lungs can influence platelet number and distribution. There is also evidence that platelets contribute to pathologic syndromes of pulmonary inflammation and thrombosis. Thus, platelets have an “amicus or adversary” relationship with the lung. Recent observations and discoveries have established new paradigms relevant to influences of platelets on lung cell and molecular biology. These new findings are in a variety of areas including thrombopoieis, nontraditional activities of platelets, new synthetic capabilities and mechanisms of post-translational gene expression, interactions of platelets with endothelial cells and contributions to alveolar capillary barrier permeability, interactions of platelets with myeloid leukocytes, and platelet involvement in stem cell signaling and vascular repair. These issues are considered in a translational approach, with an emphasis on acute lung injury and the acute respiratory distress syndrome.",,"['Bozza, Fernando A.', 'Shah, Amrapali M.', 'Weyrich, Andrew S.', 'Zimmerman, Guy A.']",,,,
,PMC,Cohabitation with farm animals in urban households with and without occupational farm work: associations between participation in educational activities and good hygiene practices in at-risk households cohabiting with farm animals,http://dx.doi.org/10.1007/s12199-008-0046-9,PMC2698226,,,"OBJECTIVES: This study was performed to investigate patterns of cohabitation with farm animals in urban households in Vientiane, Lao People’s Democratic Republic, with regard to animal-to-human disease transmission. We also investigated the association between participation in hygiene-related educational activities and good hygiene practices in households with or without cohabitation with animals. METHODS: A survey regarding cohabitation with animals, socioeconomic characteristics and participation in educational activities was conducted among 1,497 households randomly sampled from urban districts of Vientiane in 2001. Rates of satisfactory performance of recommended good hygiene practices according to a program commencing in 1996 were compared among households cohabiting with animals with or without participation in educational activities (reference group). RESULTS: Even among households not engaged in agriculture as a major source of income, 54.4, 34.9, 7.9, 3.1 and 35.7% cohabited with chickens, ducks, cattle, buffaloes and dogs, respectively. The percentage of households fulfilling the recommendations for good hygiene practices was 56.7%. The rates of satisfactory hygiene practices among households participating in health education and cohabitating with chickens, ducks or cattle were greater than those in the reference group (OR = 1.7, 95%CI = 1.2, 2.3; OR = 2.0, 95%CI = 1.3, 3.0; OR = 2.3, 95%CI = 1.0, 4.9) regardless of socioeconomic factors. Households cohabiting with animals showed poorer rates of satisfactory hygiene practices than those without animals. CONCLUSIONS: Cohabitation with farm animals is common in urban Vientiane regardless of household involvement in agriculture. Further effort is required to improve hygiene conditions, despite some positive effects of health education even in households cohabiting with animals.",,"['Somphou, Phoupasong', 'Takano, Takehito', 'Nakamura, Keiko']",,,,
,PMC,Detection of an Antigenic Group 2 Coronavirus in an Adult Alpaca with Enteritis,http://dx.doi.org/10.1128/CVI.00232-08,PMC2565933,,,Antigenic group 2 coronavirus was detected in a fecal sample of an adult alpaca by reverse transcription-PCR. The presence of alpaca coronavirus (ApCoV) in the small intestine was demonstrated by immune histochemistry with an antinucleocapsid monoclonal antibody that reacts with group 2 coronaviruses. Other common causes of diarrhea in adult camelids were not detected. We conclude that nutritional stress may have predisposed the alpaca to severe ApCoV infection.,,"['Genova, Suzanne G.', 'Streeter, Robert N.', 'Simpson, Katharine M.', 'Kapil, Sanjay']",,,,
,PMC,A duplex real-time RT-PCR assay for the detection of St. Louis encephalitis and Eastern equine encephalitis viruses,http://dx.doi.org/10.1016/j.diagmicrobio.2008.07.004,PMC2615585,,,"A duplex TaqMan real-time RT-PCR assay was developed for the detection of St. Louis encephalitis virus (SLEV) and Eastern equine encephalitis virus (EEEV), for use in human and vector surveillance. The respective targets selected for the assay were the conserved NS5 and E1 genes of the two viruses. Due to the insufficient number of NS5 sequences from SLEV strains in the GenBank database, we determined the sequence of an approximately 1-kb region for each of 25 strains of SLEV in order to select primers and probes in a conserved region. Our assay has a sensitivity of 5 gene copies/reaction for EEEV and 10 gene copies/reaction for SLEV, and it’s performance is linear over at least 6 log(10) gene copies. The assay is specific and detected all strains of SLEV (69) and EEEV (12) that were tested. An internal control ensures detection of efficient nucleic acid extraction and possible PCR inhibition.",,"['Hull, Rene', 'Nattanmai, Seela', 'Kramer, Laura D.', 'Bernard, Kristen A.', 'Tavakoli, Norma P.']",,,,
,PMC,Epstein-Barr Virus Encodes Three Bona Fide Ubiquitin-Specific Proteases,http://dx.doi.org/10.1128/JVI.01113-08,PMC2573217,,,"Manipulation of the ubiquitin proteasome system (UPS) is emerging as a common theme in viral pathogenesis. Some viruses have been shown to encode functional homologs of UPS enzymes, suggesting that a systematic identification of these products may provide new insights into virus-host cell interactions. Ubiquitin-specific proteases, collectively known as deubiquitinating enzymes (DUBs), regulate the activity of the UPS by hydrolyzing ubiquitin peptide or isopeptide bonds. The prediction of viral DUBs based on sequence similarity with known enzymes is hampered by the diversity of viral genomes. In this study sequence alignments, pattern searches, and hidden Markov models were developed for the conserved C- and H-boxes of the known DUB families and used to search the open reading frames (ORFs) of Epstein-Barr virus (EBV), a large gammaherpesvirus that has been implicated in the pathogenesis of a broad spectrum of human malignancies of lymphoid and epithelial cell origin. The searches identified a limited number of EBV ORFs that contain putative DUB catalytic domains. DUB activity was confirmed by functional assays and mutation analysis for three high scoring candidates, supporting the usefulness of this bioinformatics approach in predicting distant homologues of cellular enzymes.",,"['Sompallae, Ramakrishna', 'Gastaldello, Stefano', 'Hildebrand, Sebastian', 'Zinin, Nikolay', 'Hassink, Gerco', 'Lindsten, Kristina', 'Haas, Juergen', 'Persson, Bengt', 'Masucci, Maria G.']",,,,
,PMC,Recombinant Newcastle disease virus as a vaccine vector for cancer therapy,http://dx.doi.org/10.1038/mt.2008.181,PMC2878970,,,"Naturally occurring strains of Newcastle disease virus (NDV) are currently being investigated in multiple clinical trials for oncolytic cancer therapy in the US and abroad. We have previously reported for the first time the development of recombinant NDVs designed for enhanced cancer therapeutic efficacy. Specifically, we have shown that NDV engineered to express IL-2 generates a robust therapeutic response associated with increased tumor specific T cell infiltration after intratumoral administration in mice. We have now demonstrated that this therapeutic response is dependent on T cells and we have investigated the potential to focus the NDV-induced immune response towards a tumor-associated antigen (TAA) in order to further enhance the inherent therapeutic efficacy of NDV. We found that intratumoral treatments of tumor-bearing mice with recombinant NDV expressing a model TAA elicited an enhanced tumor specific response, resulting in a significant increase in the number of complete tumor regressions as compared to control NDV. Additionally, coadministration of NDV expression a model TAA with NDV expressing IL-2 enhanced the TAA directed response and led to more complete tumor regressions. Our results show that TAA directed immunotherapy by oncolytic recombinant NDV alone or in combination with IL-2 results in an enhanced therapeutic efficacy and warrant consideration in the development of cancer therapies based on the use of oncolytic NDV.",,"['Vigil, Adam', 'Martinez, Osvaldo', 'Chua, Mark A', 'García-Sastre, Adolfo']",,,,
,PMC,Evaluation of recombinant Onchocerca volvulus activation associated protein-1 (ASP-1) as a potent Th1-biased adjuvant with a panel of protein or peptide-based antigens and commercial inactivated vaccines,http://dx.doi.org/10.1016/j.vaccine.2008.07.028,PMC2597511,,,"Alum, the only adjuvant approved for clinical applications, can induce strong humoral (Th2) but weak cellular (Th1) immune responses. It is necessary to develop safe and effective adjuvants capable of inducing both humoral and cellular immune responses. We previously showed that activation-associated protein-1 (ASP-1) derived from Onchocerca volvulus has potent adjuvant activity. In this study, we have further evaluated the adjuvanticity of recombinant ASP-1 using a panel of recombinant proteins or synthetic peptide-based antigens, including ovalbumin (OVA), synthetic HIV peptide (HIV-p), recombinant HIV gp41 (rgp41) and HBV HBsAg, as well as three commercially available inactivated vaccines against haemorrhagic fever with renal syndrome (HFRS), Influenza and Rabies. Our results indicate that ASP-1 induced significantly higher IgG1 (Th2-associated) and IgG2a (Th1-associated) responses than alum adjuvant against OVA antigen, HIV-p, and rgp41. Consistently, it induced similar level of IgG1 responses as alum but higher level of IgG2a and IFN-γ-producing T cell responses than alum adjuvant against HBsAg. Further, ASP-1 improved both IgG1 and IgG2a responses to three commercial inactivated vaccines when used separately or in combination. In conclusion, the recombinant ASP-1, unlike alum adjuvant, is able to induce both Th1 and Th2-associated humoral responses and Th1 cellular responses, suggesting that it can be further developed as a promising adjuvant for subunit-based and inactivated vaccines.",,"['Xiao, Wenjun', 'Du, Lanying', 'Liang, Chao', 'Guan, Jie', 'Jiang, Shibo', 'Lustigman, Sara', 'He, Yuxian', 'Zhou, Yusen']",,,,
,PMC,Selective Recognition of a DNA G-Quadruplex by an Engineered Antibody,http://dx.doi.org/10.1021/bi800983u,PMC2746966,,,"Particular guanine rich nucleic acid sequences can fold into stable secondary structures called G-quadruplexes. These structures have been identified in various regions of the genome that include the telomeres, gene promoters and UTR regions, raising the possibility that they may be associated with biological function(s). Computational analysis has predicted that intramolecular G-quadruplex forming sequences are prevalent in the human genome, thus raising the desire to differentially recognize genomic G-quadruplexes. We have employed antibody phage display and competitive selection techniques to generate a single-chain antibody that shows >1000-fold discrimination between G-quadruplex and duplex DNA, and furthermore >100-fold discrimination between two related intramolecular parallel DNA G-quadruplexes. The amino acid sequence composition at the antigen binding site shows conservation within the light and heavy chains of the selected scFvs, suggesting sequence requirements for G-quadruplex recognition. Circular dichroism (CD) spectroscopic data showed that the scFv binds to the prefolded G-quadruplex and does not induce G-quadruplex structure formation. This study demonstrates the strongest discrimination that we are aware of between two intramolecular genomic G-quadruplexes.",,"['Fernando, Himesh', 'Rodriguez, Raphaël', 'Balasubramanian, Shankar']",,,,
,PMC,Predicting helix orientation for coiled-coil dimers,http://dx.doi.org/10.1002/prot.22118,PMC2562949,,,"The alpha-helical coiled coil is a structurally simple protein oligomerization or interaction motif consisting of two or more alpha helices twisted into a supercoiled bundle. Coiled coils can differ in their stoichiometry, helix orientation and axial alignment. Because of the near degeneracy of many of these variants, coiled coils pose a challenge to fold recognition methods for structure prediction. Whereas distinctions between some protein folds can be discriminated on the basis of hydrophobic/polar patterning or secondary structure propensities, the sequence differences that encode important details of coiled-coil structure can be subtle. This is emblematic of a larger problem in the field of protein structure and interaction prediction: that of establishing specificity between closely similar structures. We tested the behavior of different computational models on the problem of recognizing the correct orientation - parallel vs. antiparallel - of pairs of alpha helices that can form a dimeric coiled coil. For each of 131 examples of known structure, we constructed a large number of both parallel and antiparallel structural models and used these to asses the ability of five energy functions to recognize the correct fold. We also developed and tested three sequenced-based approaches that make use of varying degrees of implicit structural information. The best structural methods performed similarly to the best sequence methods, correctly categorizing ∼81% of dimers. Steric compatibility with the fold was important for some coiled coils we investigated. For many examples, the correct orientation was determined by smaller energy differences between parallel and antiparallel structures distributed over many residues and energy components. Prediction methods that used structure but incorporated varying approximations and assumptions showed quite different behaviors when used to investigate energetic contributions to orientation preference. Sequence based methods were sensitive to the choice of residue-pair interactions scored.",,"['Apgar, James R.', 'Gutwin, Karl N.', 'Keating, Amy E.']",,,,
,PMC,Negative Regulation of Cytoplasmic RNA-Mediated Antiviral Signaling,http://dx.doi.org/10.1016/j.cyto.2008.07.011,PMC2575845,,,"The recent, rapid progress in our understanding of cytoplasmic RNA-mediated antiviral innate immune signaling was initiated by the discovery of retinoic acid-inducible gene I (RIG-I) as a sensor of viral RNA [1]. It is now widely recognized that RIG-I and related RNA helicases, melanoma differentiated-associated gene-5 (MDA5) and laboratory of genetics and physiology-2 (LGP2), can initiate and/or regulate RNA and virus -mediated type I IFN production and antiviral responses. As with other cytokine systems, production of type I IFN is a transient process, and can be hazardous to the host if unregulated, resulting in chronic cellular toxicity or inflammatory and autoimmune diseases [2-9]. In addition, the RIG-I-like receptor (RLR) system is a fundamental target for virus-encoded immune suppression, with many indirect and direct examples of interference described. In this article, we review the current understanding of endogenous negative regulation in RLR signaling and explore direct inhibition of RLR signaling by viruses as a host immune evasion strategy.",,"['Komuro, Akihiko', 'Bamming, Darja', 'Horvath, Curt M.']",,,,
,PMC,RIBOSOMAL FRAMESHIFTING IN RESPONSE TO HYPOMODIFIED tRNAs IN XENOPUS OOCYTES,http://dx.doi.org/10.1016/j.bbrc.2008.07.118,PMC2674873,,,"We used Xenopus oocytes as an intracellular system to study ribosomal frameshifting. Microinjection of oocytes with a construct encoding the naturally-occurring UUU or AAC codon at the frameshift site demonstrated that the level of frameshifting was similar or lower than found normally in retroviral frameshifting in mammalian cells, suggesting that oocytes are a reliable system to study this event. Phenylalanine (Phe) or asparagine (Asn) tRNAs with and without the highly modified wyebutoxine (Y) or queuosine (Q) base, respectively, were microinjected to assess their ability to promote frameshifting. tRNA(Phe) (+Y) inhibited the level of frameshifting, while tRNA(Phe) (−Y) promoted frameshifting providing evidence that the hypomodified form does not act only to enhance frameshifting, but is an essential requirement. Both tRNA(Asn) (+Q) and tRNA(Asn) (−Q) were used indiscriminately in frameshifting, whether the frameshift site contained the wild type AAC, or the mutant AAU codon, suggesting that Q base modification status does not influence this process.",,"['Carlson, Bradley A.', 'Lee, Byeong Jae', 'Hatfield, Dolph L.']",,,,
,PMC,"Purification, crystallization and preliminary crystallographic analysis of avian infectious bronchitis virus nsp3 ADRP domain",http://dx.doi.org/10.1107/S1744309108024391,PMC2531276,,,"Avian infectious bronchitis virus (IBV) encodes 15 nonstructural proteins (nsps) which play crucial roles in RNA transcription and genome replication. One of them, nsp3, contains an ADRP (adenosine diphosphate-ribose-1′-phosphatase) domain which was revealed in recent studies to have ADP-ribose-1′-monophos­phatase (Appr-1′-pase) activity. Appr-1′-pase catalyzes the conversion of ADP-ribose-1′-monophosphate (Appr-1′-p) to ADP-ribose in the tRNA-splicing pathway. The gene segment encoding the IBV nsp3 ADRP domain has been cloned and expressed in Escherichia coli. The protein has been crystallized and the crystals diffracted to 1.8 Å resolution. They belonged to space group P1, with unit-cell parameters a = 41.1, b = 43.2, c = 48.9 Å, α = 78.0, β = 80.0, γ = 73.6°. Each asymmetric unit contains two molecules.",,"['Wei, Lei', 'Chen, Cheng', 'Zhao, Qi', 'Li, Chun', 'Cong, Le', 'Xu, Xiaoling', 'Ma, Yanlin', 'Liao, Ming', 'Xu, Yuanyuan', 'Rao, Zihe']",,,,
,PMC,Gene Expression Analysis of Host Innate Immune Responses during Lethal H5N1 Infection in Ferrets,http://dx.doi.org/10.1128/JVI.00691-08,PMC2573250,,,"How viral and host factors contribute to the severe pathogenicity of the H5N1 subtype of avian influenza virus infection in humans is poorly understood. We identified three clusters of differentially expressed innate immune response genes in lungs from H5N1 (A/Vietnam/1203/04) influenza virus-infected ferrets by oligonucleotide microarray analysis. Interferon response genes were more strongly expressed in H5N1-infected ferret lungs than in lungs from ferrets infected with the less pathogenic H3N2 subtype. In particular, robust CXCL10 gene expression in H5N1-infected ferrets led us to test the pathogenic role of signaling via CXCL10's cognate receptor, CXCR3, during H5N1 influenza virus infection. Treatment of H5N1-infected ferrets with the drug AMG487, a CXCR3 antagonist, resulted in a reduction of symptom severity and delayed mortality compared to vehicle treatment. We contend that unregulated host interferon responses are at least partially responsible for the severity of H5N1 infection and provide evidence that attenuating the CXCR3 signaling pathway improves the clinical course of H5N1 infection in ferrets.",,"['Cameron, Cheryl M.', 'Cameron, Mark J.', 'Bermejo-Martin, Jesus F.', 'Ran, Longsi', 'Xu, Luoling', 'Turner, Patricia V.', 'Ran, Ran', 'Danesh, Ali', 'Fang, Yuan', 'Chan, Pak-Kei M.', 'Mytle, Nutan', 'Sullivan, Timothy J.', 'Collins, Tassie L.', 'Johnson, Michael G.', 'Medina, Julio C.', 'Rowe, Thomas', 'Kelvin, David J.']",,,,
,PMC,Novel anti-HIV peptides containing multiple copies of artificially designed heptad repeat motifs,http://dx.doi.org/10.1016/j.bbrc.2008.07.134,PMC2597519,,,"The peptidic anti-HIV drug T20 (Fuzeon) and its analog C34 share a common heptad repeat (HR) sequence, but they have different functional domains, i.e., pocket- and lipid-binding domains (PBD and LBD, respectively). We hypothesize that novel anti-HIV peptides may be designed by using artificial sequences containing multiple copies of HR motifs plus zero, one or two functional domains. Surprisingly, we found that the peptides containing only the non-natural HR sequences could significantly inhibit HIV-1 infection, while addition of PBD and/or LBD to the peptides resulted in significant improvement of anti-HIV-1 activity. These results suggest that these artificial HR sequences, which may serve as structural domains, could be used as templates for the design of novel antiviral peptides against HIV and other viruses with class I fusion proteins.",,"['Shi, Weiguo', 'Qi, Zhi', 'Pan, Chungen', 'Xue, Na', 'Debnath, Asim K.', 'Qie, Jiankun', 'Jiang, Shibo', 'Liu, Keliang']",,,,
,PMC,New Tools to Battle Emerging Viruses,http://dx.doi.org/10.1016/j.mib.2008.07.003,PMC2567130,,,,,"Buchmeier, Michael J.",,,,
,PMC,HLA-DRB1(∗)0401 and HLA-DRB1(∗)0408 Are Strongly Associated with the Development of Antibodies against Interferon-β Therapy in Multiple Sclerosis,http://dx.doi.org/10.1016/j.ajhg.2008.07.006,PMC2495071,,,"The formation of antibodies to interferon-beta (IFN-β), a protein-based disease-modifying agent for multiple sclerosis (MS), is a problem in clinical practice. These antibodies may neutralize the biological effects of the protein drug, potentially decreasing its therapeutic effects. By high-resolution HLA class I and II typing we identified two HLA class II alleles associated with the development of antibodies to IFN-β. In two independent continuous and binary-trait association studies, HLA-DRB1(∗)0401 and HLA-DRB1(∗)0408 (odds ratio: 5.15)—but not other HLA alleles—were strongly associated with the development of binding and neutralizing antibodies to IFN-β. The associated HLA-DRB1(∗)04 alleles differ from nonassociated HLA-DRB1(∗)04 alleles by a glycine-to-valine substitution in position 86 of the epitope-binding alpha-helix of the HLA class II molecule. The peptide-binding motif of HLA-DRB1(∗)0401 and (∗)0408 might promote binding and presentation of an immunogenic peptide, which may eventually break T cell tolerance and facilitate antibody development to IFN-β. In summary, we identified genetic factors determining the immunogenicity of IFN-β, a protein-based disease-modifying agent for the treatment of MS.",,"['Hoffmann, Steve', 'Cepok, Sabine', 'Grummel, Verena', 'Lehmann-Horn, Klaus', 'Hackermueller, Jörg', 'Stadler, Peter F.', 'Hartung, Hans-Peter', 'Berthele, Achim', 'Deisenhammer, Florian', 'Wasmuth, Ralf', 'Hemmer, Bernhard']",,,,
,PMC,Effect of Hand Hygiene on Infectious Disease Risk in the Community Setting: A Meta-Analysis,http://dx.doi.org/10.2105/AJPH.2007.124610,PMC2446461,,,"To quantify the effect of hand-hygiene interventions on rates of gastrointestinal and respiratory illnesses and to identify interventions that provide the greatest efficacy, we searched 4 electronic databases for hand-hygiene trials published from January 1960 through May 2007 and conducted meta-analyses to generate pooled rate ratios across interventions (N=30 studies). Improvements in hand hygiene resulted in reductions in gastrointestinal illness of 31% (95% confidence intervals [CI]=19%, 42%) and reductions in respiratory illness of 21% (95% CI=5%, 34%). The most beneficial intervention was hand-hygiene education with use of nonantibacterial soap. Use of antibacterial soap showed little added benefit compared with use of nonantibacterial soap. Hand hygiene is clearly effective against gastrointestinal and, to a lesser extent, respiratory infections. Studies examining hygiene practices during respiratory illness and interventions targeting aerosol transmission are needed.",,"['Aiello, Allison E.', 'Coulborn, Rebecca M.', 'Perez, Vanessa', 'Larson, Elaine L.']",,,,
,PMC,A role for DRAK2 in the germinal center reaction and the antibody response,http://dx.doi.org/10.1080/08916930802170633,PMC3140869,,,"DAP-related apoptotic kinase-2 (DRAK2), a DAP kinase family member, is highly expressed in B and T lymphocytes in the human and the mouse. To determine whether DRAK2 plays a role in B cell activation and differentiation, we analyzed germinal centers (GCs) and the specific antibody response to NP in drak2(−/−) mice immunized with the thymus-dependent (TD) conjugated hapten NP(16)-CGG. In drak2(−/−) mice, spleen GCs were normal in size and morphology, but their number was reduced by as much as five-fold, as compared to their wild-type littermates. This was not due to a defect in B cell proliferation, as the BrdU uptake was comparable in DRAK2-deficient and wild-type B cells. Rather, the proportion of apoptotic GC B and T cells in drak2(−/−) mice was significantly higher than that in wild-type control mice, as shown by 7-AAD and TUNEL staining. In drak2(−/−) mice, the generation of high affinity IgG antibodies was impaired in spite of the seemingly normal somatic hypermutation (SHM) and class switch DNA recombination (CSR) machineries in drak2(−/−) B cells. In NP(16)-CGG-immunized drak2(−/−) mice, T cell-intrinsic Bcl-xL transgene expression increased the number of GCs and rescued the high affinity IgG response to NP. These findings suggest a novel role for DRAK2 in regulating the GC reaction and the response to TD antigens, perhaps through increased survival of T cells and enhanced B cell positive selection. They also suggest that DRAK2-deficiency is not involved in regulating intrinsic B cell apoptosis.",,"['AL-QAHTANI, AHMED', 'XU, ZHENMING', 'ZAN, HONG', 'WALSH, CRAIG M.', 'CASALI, PAOLO']",,,,
,PMC,Immune system derived from homeostatic proliferation generates normal CD8 T-cell memory but altered repertoires and diminished heterologous immune responses,http://dx.doi.org/10.1182/blood-2008-01-132464,PMC2481550,,,"The host responds to lymphopenic environments by acute homeostatic proliferation of T lymphocytes, which acquire phenotypes similar to memory cells. Using T-cell knockout (KO) mice adoptively reconstituted with splenocytes from immunologically naive mice, we examined the immune responses of an immune system derived from homeostatically proliferating (HP) T cells. HP cells mounted relatively normal acute CD8 T-cell responses to lymphocytic choriomeningitis virus (LCMV), but with altered T-cell receptor (TCR) repertoires, and they became functional memory cells capable of recall responses. Although homeostatic proliferation does not normally fully restore T-cell numbers, the CD8(+) T-cell pool was completely restored in T-cell KO mice after LCMV infection. CD4 T-cell responses were lower and not fully restored but seemed sufficient to allow for complete differentiation of CD8 memory T cells. The LCMV-immune HP mouse had an immune repertoire heavily biased with LCMV epitope-specific T cells with oligoclonal expansions. LCMV-immune HP mice had reduced cross-reactive and non–cross-reactive CD8 T-cell responses when challenged with a T cell–cross-reactive virus. Thus, whereas an HP immune system is capable of mounting relatively normal acute and memory CD8 T-cell responses, the narrowing of the T-cell repertoire may reduce immune responses to subsequently encountered pathogens.",,"['Lin, Sue-Jane', 'Chen, Alex T.', 'Welsh, Raymond M.']",,,,
,PMC,Emerging norms for the control of emerging epidemics,http://dx.doi.org/10.2471/BLT.08.051771,PMC2649476,,,,,"['McDougall, Christopher W', 'Upshur, Ross EG', 'Wilson, Kumanan']",,,,
,PMC,Cambridge textbook of bioethics,http://dx.doi.org/10.2471/BLT.08.051870,PMC2649474,,,,,"Dingwall, Robert",,,,
,PMC,A personalist approach to public-health ethics,http://dx.doi.org/10.2471/BLT.08.051193,PMC2649469,,,"First we give an overview of the historical development of public health. Then we present some public-health deontology codes and some ethical principles. We highlight difficulties in defining ethics for public health, with specific reference to three of them that concern: (i) the adaptability to public health of the classical principles of bioethics; (ii) the duty to respect and safeguard the individual while acting within the community perspective that is typical of public health; and (iii) the application-oriented nature of public health and the general lack of attention towards the ethical implications of collective interventions (compared with research). We then mention some proposals drafted from North American bioethics “principles” and utilitarian, liberal and communitarian views. Drawing from other approaches, personalism is outlined as being the theory that offers a consistent set of values and alternative principles that are relevant for public health.",,"['Petrini, Carlo', 'Gainotti, Sabina']",,,,
,PMC,Herbal medicine research and global health: an ethical analysis,http://dx.doi.org/10.2471/BLT.07.042820,PMC2649468,,,"Governments, international agencies and corporations are increasingly investing in traditional herbal medicine research. Yet little literature addresses ethical challenges in this research. In this paper, we apply concepts in a comprehensive ethical framework for clinical research to international traditional herbal medicine research. We examine in detail three key, underappreciated dimensions of the ethical framework in which particularly difficult questions arise for international herbal medicine research: social value, scientific validity and favourable risk–benefit ratio. Significant challenges exist in determining shared concepts of social value, scientific validity and favourable risk–benefit ratio across international research collaborations. However, we argue that collaborative partnership, including democratic deliberation, offers the context and process by which many of the ethical challenges in international herbal medicine research can, and should be, resolved. By “cross-training” investigators, and investing in safety-monitoring infrastructure, the issues identified by this comprehensive framework can promote ethically sound international herbal medicine research that contributes to global health.",,"['Tilburt, Jon C', 'Kaptchuk, Ted J']",,,,
,PMC,Not Waiting for Godot: Proactive Efforts to Find Potential Zoonotic Agents,http://dx.doi.org/10.3325/cmj.2008.4.564,PMC2525829,,,,,"Calisher, Charles H.",,,,
,PMC,CxCL10/CxCR3-mediated Responses Promote Immunity to Respiratory Syncytial Virus Infection by Augmenting Dendritic Cell and CD8(+) T Cell Efficacy,http://dx.doi.org/10.1002/eji.200838155,PMC2743117,,,"The induction of inflammatory cytokines during respiratory viral infections contributes to both disease pathogenesis and resolution. The present studies investigated the role of the chemokine CxCL10 and its specific receptor, CxCR3, in the host response to pulmonary respiratory syncytial virus (RSV) infection. Antibody-mediated neutralization of CxCL10 resulted in a significant increase in disease pathogenesis, including airway hyperresponsiveness (AHR), mucus gene expression, and impaired viral clearance. When the pulmonary cytokine levels were examined, only type I IFN and IL-12p70 were significantly reduced. These latter observations were reflected in reduced dendritic cell (DC) numbers and DC maturation in the lungs of RSV-infected mice treated with anti-CxCL10. Neutralization of the only known receptor for CxCL10, CxCR3, resulted in similar increases in pathogenic responses. When bone marrow-derived DC (BMDC) were incubated with CxCL10 and RSV, an upregulation of type I IFN was observed. In addition, T lymphocytes were also examined and a significant decrease in the number of RSV M2 peptide-specific CD8(+) T cells was identified. These findings highlight a previously unappreciated role for the CXCL10:CXCR3 signaling axis in RSV-infected animals by recruiting virus-specific T cells into the lung and promoting viral clearance.",,"['Lindell, Dennis M.', 'Lane, Thomas E.', 'Lukacs, Nicholas W.']",,,,
,PMC,The Impact of Respiratory Viral Infection on Wheezing Illnesses and Asthma Exacerbations,http://dx.doi.org/10.1016/j.iac.2008.03.001,PMC2504766,,,"The etiology and morbidity associated with asthma are thought to stem from both genetic factors and potentially modifiable environmental factors, such as viral infections.[1-7] Although it is unclear whether respiratory viral infections cause asthma, observational studies have demonstrated a high rate of asthma in children with a history of severe viral lower respiratory tract infections during infancy, and viruses are the associated with the majority of asthma exacerbations among both children and adults. This review will discuss the pathogens associated with virus-induced wheezing illnesses during infancy and early childhood, the association of bronchiolitis during infancy with an increased risk of childhood asthma, and the association of respiratory viruses with asthma exacerbations in older children and adults.",,"['Carroll, Kecia N.', 'Hartert, Tina V.']",,,,
,PMC,"The Epithelial Anion Transporter Pendrin Is Induced by Allergy and Rhinovirus Infection, Regulates Airway Surface Liquid, and Increases Airway Reactivity and Inflammation in an Asthma Model",,PMC2491716,,,"Asthma exacerbations can be triggered by viral infections or allergens. The Th2 cytokines IL-13 and IL-4 are produced during allergic responses and cause increases in airway epithelial cell mucus, electrolyte and water secretion into the airway surface liquid (ASL). Since ASL dehydration can cause airway inflammation and obstruction, ion transporters could play a role in pathogenesis of asthma exacerbations. We previously reported that expression of the epithelial cell anion transporter pendrin is markedly increased in response to IL-13. Here we show that pendrin plays a role in allergic airway disease and in regulation of ASL thickness. Pendrin-deficient mice had less allergen-induced airway hyperreactivity and inflammation than control mice although other aspects of the Th2 response were preserved. In cultures of IL-13-stimulated mouse tracheal epithelial cells, pendrin deficiency caused an increase in ASL thickness, suggesting that reductions in allergen-induced hyperreactivity and inflammation in pendrin-deficient mice result from improved ASL hydration. To determine whether pendrin might also play a role in virus-induced exacerbations of asthma, we measured pendrin mRNA expression in human subjects with naturally occurring common colds caused by rhinovirus and found a 4.9-fold-increase in mean expression during colds. Studies of cultured human bronchial epithelial cells indicated that this increase could be explained by the combined effects of rhinovirus and IFN-γ, a Th1 cytokine induced during virus infection. We conclude that pendrin regulates ASL thickness and may be an important contributor to asthma exacerbations induced by viral infections or allergens.",,"['Nakagami, Yasuhiro', 'Favoreto, Silvio', 'Zhen, Guohua', 'Park, Sung-Woo', 'Nguyenvu, Louis T.', 'Kuperman, Douglas A.', 'Dolganov, Gregory M.', 'Huang, Xiaozhu', 'Boushey, Homer A.', 'Avila, Pedro C.', 'Erle, David J.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.01265-08,PMC2519594,,,,,,,,,
,PMC,Taiwan Proteomics Society: An Organization Affiliated with HUPO,,PMC2500236,,,,,"['Liao, Pao-Chi', 'Wang, Andrew H.-J.', 'Chen, Shui-Tein']",,,,
,PMC,Targets of Caspase-6 Activity in Human Neurons and Alzheimer Disease,http://dx.doi.org/10.1074/mcp.M800007-MCP200,PMC2500235,,,"Caspase-6 activation occurs early in Alzheimer disease and sometimes precedes the clinical manifestation of the disease in aged individuals. The active Caspase-6 is localized in neuritic plaques, in neuropil threads, and in neurofibrillary tangles containing neurons that are not morphologically apoptotic in nature. To investigate the potential consequences of the activation of Caspase-6 in neurons, we conducted a proteomics analysis of Caspase-6-mediated cleavage of human neuronal proteins. Proteins from the cytosolic and membrane subcellular compartments were treated with recombinant active Caspase-6 and compared with undigested proteins by two-dimensional gel electrophoresis. LC/MS/MS analyses of the proteins that were cleaved identified 24 different potential protein substrates. Of these, 40% were cytoskeleton or cytoskeleton-associated proteins. We focused on the cytoskeleton proteins because these are critical for neuronal structure and function. Caspase-6 cleavage of α-Tubulin, α-Actinin-4, Spinophilin, and Drebrin was confirmed. At least one Caspase-6 cleavage site was identified for Drebrin, Spinophilin, and α-Tubulin. A neoepitope antiserum to α-Tubulin cleaved by Caspase-6 immunostained neurons, neurofibrillary tangles, neuropil threads, and neuritic plaques in Alzheimer disease and co-localized with active Caspase-6. These results imply that the early and neuritic activation of Caspase-6 in Alzheimer disease could disrupt the cytoskeleton network of neurons, resulting in impaired neuronal structure and function in the absence of cell death. This study provides novel insights into the pathophysiology of Alzheimer disease.",,"['Klaiman, Guy', 'Petzke, Tracy L.', 'Hammond, Jennifer', 'LeBlanc, Andréa C.']",,,,
,PMC,The cis-acting replication elements define human enterovirus and rhinovirus species,http://dx.doi.org/10.1261/rna.1031408,PMC2491478,,,"Replication of picornaviruses is dependent on VPg uridylylation, which is linked to the presence of the internal cis-acting replication element (cre). Cre are located within the sequence encoding polyprotein, yet at distinct positions as demonstrated for poliovirus and coxsackievirus-B3, cardiovirus, and human rhinovirus (HRV-A and HRV-B), overlapping proteins 2C, VP2, 2A, and VP1, respectively. Here we report a novel distinct cre element located in the VP2 region of the recently reported HRV-A2 species and provide evolutionary evidence of its functionality. We also experimentally interrogated functionality of recently identified HRV-B cre in the 2C region that is orthologous to the human enterovirus (HEV) cre and show that it is dispensable for replication and appears to be a nonfunctional evolutionary relic. In addition, our mutational analysis highlights two amino acids in the 2C protein that are crucial for replication. Remarkably, we conclude that each genetic clade of HRV and HEV is characterized by a unique functional cre element, where evolutionary success of a new genetic lineage seems to be associated with an invention of a novel cre motif and decay of the ancestral one. Therefore, we propose that cre element could be considered as an additional criterion for human rhinovirus and enterovirus classification.",,"['Cordey, Samuel', 'Gerlach, Daniel', 'Junier, Thomas', 'Zdobnov, Evgeny M.', 'Kaiser, Laurent', 'Tapparel, Caroline']",,,,
,PMC,A paramyxovirus-vectored intranasal vaccine against Ebola virus is immunogenic in vector-immune animals,http://dx.doi.org/10.1016/j.virol.2008.04.029,PMC2519172,,,"Ebola virus (EBOV) causes outbreaks of a highly lethal hemorrhagic fever in humans. The virus can be transmitted by direct contact as well as by aerosol and is considered a potential bioweapon. Because direct immunization of the respiratory tract should be particularly effective against infection of mucosal surfaces, we previously developed an intranasal vaccine based on replication-competent human parainfluenza virus type 3 (HPIV3) expressing EBOV glycoprotein GP (HPIV3/EboGP) and showed that it is immunogenic and protective against a high dose parenteral EBOV challenge. However, because the adult human population has considerable immunity to HPIV3, which is a common human pathogen, replication and immunogenicity of the vaccine in this population might be greatly restricted. Indeed, in the present study, replication of the vaccine in the respiratory tract of HPIV3-immune guinea pigs was found to be restricted to undetectable levels. This restriction appeared to be based on both neutralizing antibodies and cellular or other components of the immunity to HPIV3. Surprisingly, even though replication of HPIV3/EboGP was highly restricted in HPIV3-immune animals, it induced a high level of EBOV-specific antibodies that nearly equaled that obtained in HPIV3-naïve animals. We also show that the previously demonstrated presence of functional GP in the vector particle was not associated with increased replication in the respiratory tract nor with spread beyond the respiratory tract of HPIV3-naive guinea pigs, indicating that expression and functional incorporation of the attachment/penetration glycoprotein of this systemic virus did not mediate a change in tissue tropism.",,"['Yang, Lijuan', 'Sanchez, Anthony', 'Ward, Jerrold M.', 'Murphy, Brian R.', 'Collins, Peter L.', 'Bukreyev, Alexander']",,,,
,PMC,Murine Coronavirus Mouse Hepatitis Virus Is Recognized by MDA5 and Induces Type I Interferon in Brain Macrophages/Microglia,http://dx.doi.org/10.1128/JVI.01199-08,PMC2566260,,,"The coronavirus mouse hepatitis virus (MHV) induces a minimal type I interferon (IFN) response in several cell types in vitro despite the fact that the type I IFN response is important in protecting the mouse from infection in vivo. When infected with MHV, mice deficient in IFN-associated receptor expression (IFNAR(−/−)) became moribund by 48 h postinfection. MHV also replicated to higher titers and exhibited a more broad tissue tropism in these mice, which lack a type I IFN response. Interestingly, MHV induced IFN-β in the brains and livers, two main targets of MHV replication, of infected wild-type mice. MHV infection of primary cell cultures indicates that hepatocytes are not responsible for the IFN-β production in the liver during MHV infection. Furthermore, macrophages and microglia, but not neurons or astrocytes, are responsible for IFN-β production in the brain. To determine the pathway by which MHV is recognized in macrophages, IFN-β mRNA expression was quantified following MHV infection of a panel of primary bone marrow-derived macrophages generated from mice lacking different pattern recognition receptors (PRRs). Interestingly, MDA5, a PRR thought to recognize primarily picornaviruses, was required for recognition of MHV. Thus, MHV induces type I IFN in macrophages and microglia in the brains of infected animals and is recognized by an MDA5-dependent pathway in macrophages. These findings suggest that secretion of IFN-β by macrophages and microglia plays a role in protecting the host from MHV infection of the central nervous system.",,"['Roth-Cross, Jessica K.', 'Bender, Susan J.', 'Weiss, Susan R.']",,,,
,PMC,"Gain, Preservation, and Loss of a Group 1a Coronavirus Accessory Glycoprotein",http://dx.doi.org/10.1128/JVI.01031-08,PMC2566247,,,"Coronaviruses are positive-strand RNA viruses of extraordinary genetic complexity and diversity. In addition to a common set of genes for replicase and structural proteins, each coronavirus may carry multiple group-specific genes apparently acquired through relatively recent heterologous recombination events. Here we describe an accessory gene, ORF3, unique to canine coronavirus type I (CCoV-I) and characterize its product, glycoprotein gp3. Whereas ORF3 is conserved in CCoV-I, only remnants remain in CCoV-II and CCoV-II-derived porcine and feline coronaviruses. Our findings provide insight into the evolutionary history of coronavirus group 1a and into the dynamics of gain and loss of accessory genes.",,"['Lorusso, Alessio', 'Decaro, Nicola', 'Schellen, Pepijn', 'Rottier, Peter J. M.', 'Buonavoglia, Canio', 'Haijema, Bert-Jan', 'de Groot, Raoul J.']",,,,
,PMC,Immunosuppression Enhances Oncolytic Adenovirus Replication and Antitumor Efficacy in the Syrian Hamster Model,,PMC3437752,,,"We recently described an immunocompetent Syrian hamster model for oncolytic adenoviruses (Ads) that permits virus replication in tumor cells as well as some normal tissues. This model allows exploration of interactions between the virus, tumor, normal organs, and host immune system that could not be examined in the immunodeficient or nonpermissive animal models previously used in the oncolytic Ad field. Here we asked whether the immune response to oncolytic Ad enhances or limits antitumor efficacy. We first determined that cyclophosphamide (CP) is a potent immunosuppressive agent in the Syrian hamster and that CP alone had no effect on tumor growth. Importantly, we found that the antitumor efficacy of oncolytic Ads was significantly enhanced in immunosuppressed animals. In animals that received virus therapy plus immunosuppression, significant differences were observed in tumor histology, and in many cases little viable tumor remained. Notably, we also determined that immunosuppression allowed intratumoral virus levels to remain elevated for prolonged periods. Although favorable tumor responses can be achieved in immunocompetent animals, the rate of virus clearance from the tumor may lead to varied antitumor efficacy. Immunosuppression, therefore, allows sustained Ad replication and oncolysis, which leads to substantially improved suppression of tumor growth.",,"['Thomas, Maria A', 'Spencer, Jacqueline F', 'Toth, Karoly', 'Sagartz, John E', 'Phillips, Nancy J', 'Wold, William SM']",,,,
,PMC,Lensless high-resolution on-chip optofluidic microscopes for Caenorhabditis elegans and cell imaging,http://dx.doi.org/10.1073/pnas.0804612105,PMC2488383,,,"Low-cost and high-resolution on-chip microscopes are vital for reducing cost and improving efficiency for modern biomedicine and bioscience. Despite the needs, the conventional microscope design has proven difficult to miniaturize. Here, we report the implementation and application of two high-resolution (≈0.9 μm for the first and ≈0.8 μm for the second), lensless, and fully on-chip microscopes based on the optofluidic microscopy (OFM) method. These systems abandon the conventional microscope design, which requires expensive lenses and large space to magnify images, and instead utilizes microfluidic flow to deliver specimens across array(s) of micrometer-size apertures defined on a metal-coated CMOS sensor to generate direct projection images. The first system utilizes a gravity-driven microfluidic flow for sample scanning and is suited for imaging elongate objects, such as Caenorhabditis elegans; and the second system employs an electrokinetic drive for flow control and is suited for imaging cells and other spherical/ellipsoidal objects. As a demonstration of the OFM for bioscience research, we show that the prototypes can be used to perform automated phenotype characterization of different Caenorhabditis elegans mutant strains, and to image spores and single cellular entities. The optofluidic microscope design, readily fabricable with existing semiconductor and microfluidic technologies, offers low-cost and highly compact imaging solutions. More functionalities, such as on-chip phase and fluorescence imaging, can also be readily adapted into OFM systems. We anticipate that the OFM can significantly address a range of biomedical and bioscience needs, and engender new microscope applications.",,"['Cui, Xiquan', 'Lee, Lap Man', 'Heng, Xin', 'Zhong, Weiwei', 'Sternberg, Paul W.', 'Psaltis, Demetri', 'Yang, Changhuei']",,,,
,PMC,Functional genomics as a tool in virus research,http://dx.doi.org/10.1007/s12088-008-0032-3,PMC3450177,,,"Genomics is the study of an organism’s entire genome. It started out as a great scientific endeavor in the 1990s which aimed to sequence the complete genomes of certain biological species. However viruses are not new to this field as complete viral genomes have routinely been sequenced since the past thirty years. The ‘genomic era’ has been said to have revolutionized biology. This knowledge of full genomes has created the field of functional genomics in today’s post-genomic era, which, is in most part concerned with the studies on the expression of the organism’s genome under different conditions. This article is an attempt to introduce its readers to the application of functional genomics to address and answer several complex biological issues in virus research.",,"['Ratra, Ruchi', 'Lal, Sunil K.']",,,,
,PMC,Structural Flexibility of the Pentameric SARS Coronavirus Envelope Protein Ion Channel,http://dx.doi.org/10.1529/biophysj.108.133041,PMC2527252,,,"Coronaviruses contain a small envelope membrane protein with cation-selective ion channel activity mediated by its transmembrane domain (ETM). In a computational study, we proposed that ion channel activity can be explained by either of two similar ETM homopentameric transmembrane α-helical bundles, related by a ∼50° rotation of the helices. Later, we tested this prediction, using site-specific infrared dichroism of a lysine-flanked isotopically labeled ETM peptide from the virus responsible for the severe acute respiratory syndrome, SARS, reconstituted in lipid bilayers. However, the data were consistent with the presence of a kink at the center of the ETM α-helix, and it did not fit completely either computational model. Herein, we have used native ETM, without flanking lysines, and show that the helix orientation is now consistent with one of the predicted models. ETM only produced one oligomeric form, pentamers, in the lipid-mimic detergent dodecylphosphocholine and in perfluorooctanoic acid. We thus report the correct backbone model for the pentameric α-helical bundle of ETM. The disruptive effects caused by terminal lysines probably highlight the conformational flexibility required during ion channel function.",,"['Parthasarathy, Krupakar', 'Ng, Lifang', 'Lin, Xin', 'Liu, Ding Xiang', 'Pervushin, Konstantin', 'Gong, Xiandi', 'Torres, Jaume']",,,,
,PMC,Brain Extracellular Matrix in Neurodegeneration,http://dx.doi.org/10.1111/j.1750-3639.2008.00195.x,PMC2742568,,,"The role of extracellular matrix (ECM) in neurological development, function and degeneration has evolved from a simplistic physical adhesion to a system of intricate cellular signaling. While most cells require ECM adhesion to survive, it is now clear that differentiated function is intimately dependent upon cellular interaction with the ECM. Therefore, it is not surprising that the ECM is increasingly found to be involved in the enigmatic process of neurodegeneration. Descriptive studies of human neurodegenerative disorders and experimental studies of animal models of neurodegeneration have begun to define potential mechanisms of ECM disruption that can lead to synaptic and neuronal loss.",,"['Bonneh-Barkay, Dafna', 'Wiley, Clayton A.']",,,,
,PMC,Frameshifting RNA Pseudoknots: Structure and Mechanism,http://dx.doi.org/10.1016/j.virusres.2008.06.008,PMC2670756,,,"Programmed ribosomal frameshifting (PRF) is one of multiple translational recoding processes that fundamentally alters triplet decoding of the messenger RNA by the elongating ribosome. The ability of the ribosome to change translational reading frames in the −1 direction (−1 PRF) is employed by many positive strand RNA viruses, including economically important plant viruses and many human pathogens such as retroviruses, e.g., HIV-1, and coronaviruses, e.g., the causative agent of severe acute respiratory syndrome (SARS), in order to properly express their genomes. −1 PRF is programmed by a bipartite signal embedded in the mRNA and includes a heptanucleotide “slip site” over which the paused ribosome “backs up” by one nucleotide, and a downstream stimulatory element, either an RNA pseudoknot or a very stable RNA stem-loop. These two elements are separated by 6–8 nucleotides, a distance that places the 5′ edge of the downstream stimulatory element in direct contact with the mRNA entry channel of the 30S ribosomal subunit. The precise mechanism by which the downstream RNA stimulates −1 PRF by the translocating ribosome remains unclear. This review summarizes the recent structural and biophysical studies of RNA pseudoknots and places this work in the context of our evolving mechanistic understanding of translation elongation. Support for the hypothesis that the downstream stimulatory element provides a kinetic barrier to the ribosome mediated unfolding is discussed.",,"['Giedroc, David P.', 'Cornish, Peter V.']",,,,
,PMC,ACE2 is expressed in mouse adipocytes and regulated by a high-fat diet,http://dx.doi.org/10.1152/ajpregu.00183.2008,PMC2536864,,,"Adipose tissue expresses components of the renin-angiotensin system (RAS). Angiotensin converting enzyme (ACE2), a new component of the RAS, catabolizes the vasoconstrictor peptide ANG II to form the vasodilator angiotensin 1-7 [ANG-(1-7)]. We examined whether adipocytes express ACE2 and its regulation by manipulation of the RAS and by high-fat (HF) feeding. ACE2 mRNA expression increased (threefold) during differentiation of 3T3-L1 adipocytes and was not regulated by manipulation of the RAS. Male C57BL/6 mice were fed low- (LF) or high-fat (HF) diets for 1 wk or 4 mo. At 1 wk of HF feeding, adipose expression of angiotensinogen (twofold) and ACE2 (threefold) increased, but systemic angiotensin peptide concentrations and blood pressure were not altered. At 4 mo of HF feeding, adipose mRNA expression of angiotensinogen (twofold) and ACE2 (threefold) continued to be elevated, and liver angiotensinogen expression increased (twofold). However, adipose tissue from HF mice did not exhibit elevated ACE2 protein or activity. Increased expression of ADAM17, a protease responsible for ACE2 shedding, coincided with reductions in ACE2 activity in 3T3-L1 adipocytes, and an ADAM17 inhibitor decreased media ACE2 activity. Moreover, ADAM17 mRNA expression was increased in adipose tissue from 4-mo HF-fed mice, and plasma ACE2 activity increased. However, HF mice exhibited marked increases in plasma angiotensin peptide concentrations (LF: 2,141 ± 253; HF: 6,829 ± 1,075 pg/ml) and elevated blood pressure. These results demonstrate that adipocytes express ACE2 that is dysregulated in HF-fed mice with elevated blood pressure compared with LF controls.",,"['Gupte, Manisha', 'Boustany-Kari, Carine M.', 'Bharadwaj, Kalyani', 'Police, Sara', 'Thatcher, Sean', 'Gong, Ming C.', 'English, Victoria L.', 'Cassis, Lisa A.']",,,,
,PMC,NMR assignment of the nonstructural protein nsp3(1066–1181) from SARS-CoV,http://dx.doi.org/10.1007/s12104-008-9104-x,PMC2776825,,,"Sequence-specific NMR assignments of the globular core comprising the residues 1066–1181 within the non-structural protein nsp3e from the SARS coronavirus have been obtained using triple-resonance NMR experiments with the uniformly [(13)C,(15)N]-labeled protein. The backbone and side chain assignments are nearly complete, providing the basis for the ongoing NMR structure determination. A preliminary identification of regular secondary structures has been derived from the (13)C chemical shifts.",,"['Serrano, Pedro', 'Johnson, Margaret A.', 'Chatterjee, Amarnath', 'Pedrini, Bill', 'Wüthrich, Kurt']",,,,
,PMC,Design and integration of an all-in-one biomicrofluidic chip,http://dx.doi.org/10.1063/1.2966453,PMC2716927,,,"We demonstrate a highly integrated microfluidic chip with the function of DNA amplification. The integrated chip combines giant electrorheological-fluid actuated micromixer and micropump with a microheater array, all formed using soft lithography. Internal functional components are based on polydimethylsiloxane (PDMS) and silver∕carbon black-PDMS composites. The system has the advantages of small size with a high degree of integration, high polymerase chain reaction efficiency, digital control and simple fabrication at low cost. This integration approach shows promise for a broad range of applications in chemical synthesis and biological sensing∕analysis, as different components can be combined to target desired functionalities, with flexible designs of different microchips easily realizable through soft lithography.",,"['Liu, Liyu', 'Cao, Wenbin', 'Wu, Jingbo', 'Wen, Weijia', 'Chang, Donald Choy', 'Sheng, Ping']",,,,
,PMC,A likelihood-based method for real-time estimation of the serial interval and reproductive number of an epidemic,http://dx.doi.org/10.1002/sim.3136,PMC3951165,,,"We present a method for the simultaneous estimation of the basic reproductive number, R(0), and the serial interval for infectious disease epidemics, using readily available surveillance data. These estimates can be obtained in real time to inform an appropriate public health response to the outbreak. We show how this methodology, in its most simple case, is related to a branching process and describe similarities between the two that allow us to draw parallels which enable us to understand some of the theoretical properties of our estimators. We provide simulation results that illustrate the efficacy of the method for estimating R(0) and the serial interval in real time. Finally, we implement our proposed method with data from three infectious disease outbreaks.",,"['White, L. Forsberg', 'Pagano, M.']",,,,
,PMC,DNA Polymerases as Therapeutic Targets,http://dx.doi.org/10.1021/bi801179f,PMC2692436,,,"Numerous pathological states including cancer, autoimmune diseases, and viral/bacterial infections are often attributed to uncontrollable DNA replication. Inhibiting this essential biological process provides an obvious therapeutic target against these diseases. A logical target is the DNA polymerase, the enzyme responsible for catalyzing the addition of mononucleotides into a growing polymer using a DNA or RNA template as a guide for directing each incorporation event. This review provides a summary of therapeutic agents that target polymerase activity. A discussion of the biological function and mechanism of polymerases is first provided to illustrate the strategy for therapeutic intervention as well as the rational design of various nucleoside analogs that inhibit various polymerases associated with viral infections and cancer. The development of nucleoside and non-nucleoside inhibitors as anti-viral agents is discussed with particular emphasis on their mechanism of action, structure-activity relationships, toxicity, and mechanism of resistance. In addition, commonly used anti-cancer agents are described to illustrate the similarities and differences associated with various nucleoside analogs as therapeutic agents. Finally, new therapeutic approaches are discussed that include the inhibition of selective polymerases involved in DNA repair and/or translesion DNA synthesis as anti-cancer agents.",,"Berdis, Anthony J.",,,,
,PMC,Comparison of the Luminex xTAG Respiratory Viral Panel with In-House Nucleic Acid Amplification Tests for Diagnosis of Respiratory Virus Infections,http://dx.doi.org/10.1128/JCM.00878-08,PMC2546709,,,"Detection of respiratory viruses using sensitive real-time nucleic acid amplification tests (NATs) is invaluable for patient and outbreak management. However, the wide range of potential respiratory virus pathogens makes testing using individual real-time NATs expensive and laborious. The objective of this study was to compare the detection of respiratory virus targets using the Luminex xTAG respiratory viral panel (RVP) assay with individual real-time NATs used at the Provincial Laboratory of Public Health, Calgary, Alberta, Canada. The study included 1,530 specimens submitted for diagnosis of respiratory infections from December 2006 to May 2007. Direct-fluorescent-antigen-positive nasopharyngeal samples were excluded from this study. A total of 690 and 643 positives were detected by RVP and in-house NATs, respectively. Kappa correlation between in-house NATs and RVP for all targets ranged from 0.721 to 1.000. The majority of specimens missed by in-house NATs (96.7%) were positive for picornaviruses. Samples missed by RVP were mainly positive for adenovirus (51.7%) or respiratory syncytial virus (27.5%) by in-house NATs and in general had low viral loads. RVP allows for multiplex detection of 20 (and differentiation between 19) respiratory virus targets with considerable time and cost savings compared with alternative NATs. Although this first version of the RVP assay has lower sensitivity than in-house NATs for detection of adenovirus, it has good sensitivity for other targets. The identification of picornaviruses and coronaviruses and concurrent typing of influenza A virus by RVP, which are not currently included in our diagnostic testing algorithm, will improve our diagnosis of respiratory tract infections.",,"['Pabbaraju, Kanti', 'Tokaryk, Kara L.', 'Wong, Sallene', 'Fox, Julie D.']",,,,
,PMC,The Transmembrane Domain of the Severe Acute Respiratory Syndrome Coronavirus ORF7b Protein Is Necessary and Sufficient for Its Retention in the Golgi Complex,http://dx.doi.org/10.1128/JVI.00784-08,PMC2546951,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) ORF7b (also called 7b) protein is an integral membrane protein that is translated from a bicistronic open reading frame encoded within subgenomic RNA 7. When expressed independently or during virus infection, ORF7b accumulates in the Golgi compartment, colocalizing with both cis- and trans-Golgi markers. To identify the domains of this protein that are responsible for Golgi localization, we have generated a set of mutant proteins and analyzed their subcellular localizations by indirect immunofluorescence confocal microscopy. The N- and C-terminal sequences are dispensable, but the ORF7b transmembrane domain (TMD) is essential for Golgi compartment localization. When the TMD of human CD4 was replaced with the ORF7b TMD, the resulting chimeric protein localized to the Golgi complex. Scanning alanine mutagenesis identified two regions in the carboxy-terminal portion of the TMD that eliminated the Golgi complex localization of the chimeric CD4 proteins or ORF7b protein. Collectively, these data demonstrate that the Golgi complex retention signal of the ORF7b protein resides solely within the TMD.",,"['Schaecher, Scott R.', 'Diamond, Michael S.', 'Pekosz, Andrew']",,,,
,PMC,Genomic Analysis Reveals Age-Dependent Innate Immune Responses to Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.00489-08,PMC2546950,,,"The relationship between immunosenescence and the host response to virus infection is poorly understood at the molecular level. Two different patterns of pulmonary host responses to virus were observed when gene expression profiles from severe acute respiratory syndrome coronavirus (SARS-CoV)-infected young mice that show minimal disease were compared to those from SARS-CoV-infected aged mice that develop pneumonitis. In young mice, genes related to cellular development, cell growth, and cell cycle were downregulated during peak viral replication, and these transcripts returned to basal levels as virus was cleared. In contrast, aged mice had a greater number of upregulated immune response and cell-to-cell signaling genes, and the expression of many genes was sustained even after viral clearance, suggesting an exacerbated host response to virus. Interestingly, in SARS-CoV-infected aged mice, a subset of genes, including Tnfa, Il6, Ccl2, Ccl3, Cxcl10, and Ifng, was induced in a biphasic pattern that correlated with peak viral replication and a subsequent influx of lymphocytes and severe histopathologic changes in the lungs. We provide insight into gene expression profiles and molecular signatures underlying immunosenescence in the context of the host response to viral infection.",,"['Baas, Tracey', 'Roberts, Anjeanette', 'Teal, Thomas H.', 'Vogel, Leatrice', 'Chen, Jun', 'Tumpey, Terrence M.', 'Katze, Michael G.', 'Subbarao, Kanta']",,,,
,PMC,Enzootic Nasal Tumor Virus Envelope Requires a Very Acidic pH for Fusion Activation and Infection,http://dx.doi.org/10.1128/JVI.00648-08,PMC2546887,,,"Enzootic nasal tumor virus (ENTV) is a close relative of jaagsiekte sheep retrovirus (JSRV), and the two viruses use the same receptor, hyaluronidase 2 (Hyal2), for cell entry. We report here that, unlike the JSRV envelope (Env) protein, the ENTV Env protein does not induce cell fusion at pHs of 5.0 and above but requires a much lower pH (4.0 to 4.5) for fusion to occur. The entry of ENTV Env pseudovirions was substantially inhibited by bafilomycin A1 (BafA1) but was surprisingly enhanced by lysosomotropic agents and lysosomal protease inhibitors following a 4- to 6-h treatment period; of note, prolonged treatment with BafA1 or ammonium chloride completely blocked ENTV entry. Unlike typical pH-dependent viruses, ENTV Env pseudovirions were virtually resistant to inactivation at a low pH (4.5 or 5.0). Using chimeras formed from ENTV and JSRV Env proteins, we demonstrated that the transmembrane (TM) subunit of ENTV Env is primarily responsible for its unusually low pH requirement for fusion but found that the surface (SU) subunit of ENTV Env also critically influences its relatively low and pH-dependent fusion activity. Furthermore, the poor infectivity of ENTV pseudovirions in human cells was significantly improved by either replacing the SU subunit of ENTV Env with that of JSRV Env or overexpressing the functional Hyal2 receptor in target cells, suggesting that ENTV SU-Hyal2 interaction is likely to be the limiting step for viral infectivity. Collectively, our data reveal that the fusogenicity of ENTV Env is intrinsically lower than that of JSRV Env and that ENTV requires a more acidic pH for fusion, which may occur in an intracellular compartment(s) distinct from that used by JSRV.",,"['Côté, Marceline', 'Kucharski, Thomas J.', 'Liu, Shan-Lu']",,,,
,PMC,Stem Cells and Cell Therapies in Lung Biology and Lung Diseases,http://dx.doi.org/10.1513/pats.200804-037DW,PMC2645238,,,,,"['Weiss, Daniel J.', 'Kolls, Jay K.', 'Ortiz, Luis A.', 'Panoskaltsis-Mortari, Angela', 'Prockop, Darwin J.']",,,,
,PMC,Commentary on “Increased MCP-1 and Microglia in Various regions of Human Alcoholic Brain”,http://dx.doi.org/10.1016/j.expneurol.2008.05.016,PMC2591065,,,,,"['Sullivan, Edith V.', 'Zahr, Natalie M.']",,,,
,PMC,Imported malaria in the UK,http://dx.doi.org/10.1136/bmj.a135,PMC2453247,,,Is rising because of failure to comply with prophylaxis or to seek travel health advice,,"Zuckerman, Jane N",,,,
,PMC,A rapid point of care immunoswab assay for SARS-CoV detection,http://dx.doi.org/10.1016/j.jviromet.2008.05.023,PMC2678951,,,"The emergence of severe acute respiratory syndrome (SARS) resulted in several outbreaks worldwide. Early tests for diagnosis were not always conclusive in identifying a SARS suspected patient. Nucleocapsid protein (NP) is the most predominant virus derived structural protein which is shed in high amounts in serum and nasopharyngeal aspirate during the first week of infection. As part of such efforts, a simple, easy to use immunoswab method was developed by generating a panel of monoclonal antibodies (MAbs), Bispecific MAbs and chicken polyclonal IgY antibody against the SARS-CoV nucleocapsid protein (NP). Employing the MAb-based immunoswab, an NP concentration of 200 pg/mL in saline and pig nasopharyngeal aspirate, and 500 pg/mL in rabbit serum were detected. BsMAb-based immunoswabs detected an NP concentration of 20 pg/mL in saline, 500 pg/mL in rabbit serum and 20–200 pg/mL in pig nasopharyngeal aspirate. Polyclonal IgY-based immunoswabs detected an NP concentration of 10 pg/mL in pig nasopharyngeal aspirate providing the most sensitive SARS point of care assay. Results show that the robust immunoswab method of detecting SARS-CoV NP antigen can be developed into an easy and effective way of identifying SARS suspected individuals during a future SARS epidemic, thereby reducing and containing the transmission. The key feature of this simple immunoswab diagnostic assay is its ability to detect the presence of the SARS-CoV antigen within 45–60 min with the availability of the body fluid samples.",,"['Kammila, Sriram', 'Das, Dipankar', 'Bhatnagar, Pravin K.', 'Sunwoo, Hoon H.', 'Zayas-Zamora, Gustavo', 'King, Malcolm', 'Suresh, Mavanur R.']",,,,
,PMC,Evaluation of Three Real-Time PCR Assays for Detection of Mycoplasma pneumoniae in an Outbreak Investigation,http://dx.doi.org/10.1128/JCM.00440-08,PMC2546712,,,"We compared the performances of three recently optimized real-time PCR assays derived from distinct genomic regions of Mycoplasma pneumoniae during an outbreak. Comprehensive evaluation established that a newly described toxin gene represents a superior target for detecting M. pneumoniae DNA in clinical specimens, although use of multiple targets may increase testing confidence.",,"['Winchell, Jonas M.', 'Thurman, Kathleen A.', 'Mitchell, Stephanie L.', 'Thacker, W. Lanier', 'Fields, Barry S.']",,,,
,PMC,Comparative Study of Nasopharyngeal Aspirate and Nasal Swab Specimens for Diagnosis of Acute Viral Respiratory Infection,http://dx.doi.org/10.1128/JCM.01209-08,PMC2546706,,,"Paired nasopharyngeal aspirate (NPA) and nasal swab (NS) samples from 475 children hospitalized for acute respiratory infection were studied for the detection of influenza virus, parainfluenza virus, respiratory syncytial virus, and adenovirus by immunofluorescence test, viral culture, and multiplex PCR assay. The overall sensitivity of viral detection with NPA specimens was higher than that obtained with NS specimens.",,"['Sung, Rita Y. T.', 'Chan, Paul K. S.', 'Choi, Kai C.', 'Yeung, Apple C. M.', 'Li, Albert M.', 'Tang, Julian W.', 'Ip, Margaret', 'Tsen, Tracy', 'Nelson, E. Anthony S.']",,,,
,PMC,Identification and Biochemical Characterization of Small-Molecule Inhibitors of West Nile Virus Serine Protease by a High-Throughput Screen,http://dx.doi.org/10.1128/AAC.01508-07,PMC2533463,,,"West Nile virus and dengue virus are mosquito-borne flaviviruses that cause a large number of human infections each year. No vaccines or chemotherapeutics are currently available. These viruses encode a serine protease that is essential for polyprotein processing, a required step in the viral replication cycle. In this study, a high-throughput screening assay for the West Nile virus protease was employed to screen ∼32,000 small-molecule compounds for identification of inhibitors. Lead inhibitor compounds with three distinct core chemical structures (1 to 3) were identified. In a secondary screening of selected compounds, two compounds, belonging to the 8-hydroxyquinoline family (compounds A and B) and containing core structure 1, were identified as potent inhibitors of the West Nile virus protease, with K(i) values of 3.2 ± 0.3 μM and 3.4 ± 0.6 μM, respectively. These compounds inhibited the dengue virus type 2 protease with K(i) values of 28.6 ± 5.1 μM and 30.2 ± 8.6 μM, respectively, showing some selectivity in the inhibition of these viral proteases. However, the compounds show no inhibition of cellular serine proteases, trypsin, or factor Xa. Kinetic analysis and molecular docking of compound B onto the known crystal structure of the West Nile virus protease indicate that the inhibitor binds in the substrate-binding cleft. Furthermore, compound B was capable of inhibiting West Nile virus RNA replication in cultured Vero cells (50% effective concentration, 1.4 ± 0.4 μM; selectivity index, 100), presumably by inhibition of polyprotein processing.",,"['Mueller, Niklaus H.', 'Pattabiraman, Nagarajan', 'Ansarah-Sobrinho, Camilo', 'Viswanathan, Prasanth', 'Pierson, Theodore C.', 'Padmanabhan, R.']",,,,
,PMC,Preferential Cytolysis of Peripheral Memory CD4(+) T Cells by In Vitro X4-Tropic Human Immunodeficiency Virus Type 1 Infection before the Completion of Reverse Transcription,http://dx.doi.org/10.1128/JVI.00773-08,PMC2546913,,,"CD4(+) T-cell depletion is the hallmark of AIDS pathogenesis. Multiple mechanisms may contribute to the death of productively infected CD4(+) T cells and innocent-bystander cells. In this study, we characterize a novel mechanism in which human immunodeficiency virus type 1 (HIV-1) infection preferentially depletes peripheral memory CD4(+) T cells before the completion of reverse transcription. Using a recombinant HIV-1 carrying the green fluorescent protein reporter gene, we demonstrate that memory CD4(+) T cells were susceptible to infection-induced cell death at a low multiplicity of infection. Infected memory CD4(+) T cells underwent rapid necrotic cell death. Killing of host cells was dependent on X4 envelope-mediated viral fusion, but not on virion-associated Vpr or Nef. In contrast to peripheral resting CD4(+) T cells, CD4(+) T cells stimulated by mitogen or certain cytokines were resistant to HIV-1-induced early cell death. These results demonstrate that early steps in HIV-1 infection have a detrimental effect on certain subsets of CD4(+) T cells. The early cell death may serve as a selective disadvantage for X4-tropic HIV-1 in acute infection but may play a role in accelerated disease progression, which is associated with the emergence of X4-tropic HIV-1 in the late stage of AIDS.",,"['Zhou, Yan', 'Shen, Lin', 'Yang, Hung-Chih', 'Siliciano, Robert F.']",,,,
,PMC,Autophagosome Supports Coxsackievirus B3 Replication in Host Cells,http://dx.doi.org/10.1128/JVI.00641-08,PMC2546883,,,"Recent studies suggest a possible takeover of host antimicrobial autophagy machinery by positive-stranded RNA viruses to facilitate their own replication. In the present study, we investigated the role of autophagy in coxsackievirus replication. Coxsackievirus B3 (CVB3), a picornavirus associated with viral myocarditis, causes pronounced intracellular membrane reorganization after infection. We demonstrate that CVB3 infection induces an increased number of double-membrane vesicles, accompanied by an increase of the LC3-II/LC3-I ratio and an accumulation of punctate GFP-LC3-expressing cells, two hallmarks of cellular autophagosome formation. However, protein expression analysis of p62, a marker for autophagy-mediated protein degradation, showed no apparent changes after CVB3 infection. These results suggest that CVB3 infection triggers autophagosome formation without promoting protein degradation by the lysosome. We further examined the role of the autophagosome in CVB3 replication. We demonstrated that inhibition of autophagosome formation by 3-methyladenine or small interfering RNAs targeting the genes critical for autophagosome formation (ATG7, Beclin-1, and VPS34 genes) significantly reduced viral replication. Conversely, induction of autophagy by rapamycin or nutrient deprivation resulted in increased viral replication. Finally, we examined the role of autophagosome-lysosome fusion in viral replication. We showed that blockage of the fusion by gene silencing of the lysosomal protein LAMP2 significantly promoted viral replication. Taken together, our results suggest that the host's autophagy machinery is activated during CVB3 infection to enhance the efficiency of viral replication.",,"['Wong, Jerry', 'Zhang, Jingchun', 'Si, Xiaoning', 'Gao, Guang', 'Mao, Ivy', 'McManus, Bruce M.', 'Luo, Honglin']",,,,
,PMC,CD4 T Cells Mediate Axonal Damage and Spinal Cord Motor Neuron Apoptosis in Murine P0(106–125)-Induced Experimental Autoimmune Neuritis,http://dx.doi.org/10.2353/ajpath.2008.071101,PMC2438288,,,"The pathogenesis of inflammatory autoimmune diseases of the peripheral nervous system, leading to demyelination and/or axonal damage, remains incompletely understood. In particular, it is controversial regarding the extent to which (i) autoimmune-mediated destruction of peripheral nerves results in secondary damage of the central nervous system, and (ii) CD4 and CD8 T cells contribute to disease. To address these issues, we applied the murine model of P0(106–125)-induced experimental autoimmune neuritis. Immunization of C57BL/6 mice with P0(106–125) resulted in severe axonal damage and mild demyelination. Importantly, these mice developed a “dying-back” axonopathy with apoptosis of a large fraction of neurons in the anterior horn of the lumbar and thoracic spinal cord and a progressive neurogenic muscular atrophy. T cell-depletion experiments identified CD4, but not CD8, T cells as important mediators of experimental autoimmune neuritis. CD4 T cells represented the major cellular source of antigen-specific interferon-γ and interleukin-17 production, regulated the number of tumor necrosis factor-positive and inducible nitric oxide synthase-positive macrophages in the diseased sciatic nerve, and mediated axonal damage and subsequent neuronal apoptosis and neurogenic muscular atrophy. In contrast, the demyelination of peripheral nerves was only slightly ameliorated in CD4 T cell-depleted mice. In conclusion, P0(106–125)-induced experimental autoimmune neuritis is a CD4 T cell-mediated autoimmune disease that affects both the peripheral and central nervous systems.",,"['Brunn, Anna', 'Utermöhlen, Olaf', 'Carstov, Mariana', 'Ruiz, Monica Sánchez', 'Miletic, Hrvoje', 'Schlüter, Dirk', 'Deckert, Martina']",,,,
,PMC,Role of nitric oxide in management of acute respiratory distress syndrome,http://dx.doi.org/10.4103/1817-1737.41914,PMC2700444,19561888,CC BY,"The current mortality rate of patients suffering from acute respiratory distress syndrome (ARDS) is between 45% and 92%, with most dying within the first two weeks of the illness. In an effort to combat such an alarmingly high mortality rate, various treatment therapies such as low tidal volume ventilation strategies, corticosteroid therapy, and use of nitric oxide (NO) have been attempted in the management of patients with ARDS. Three cases which were admitted to the ICU and confirmed to have ARDS were unable to be weaned from ventilatory support, and nitric oxide therapy was initiated. It improved patients' oxygenation for short periods of time but did not affect the mortality. The patients could not be weaned from the ventilator and expired.",2008 Jul-Sep,"['Akmal, A. H.', 'Hasan, Mohd']",Ann Thorac Med,,,
,PMC,Community of care,,PMC2464787,,,,,"['Yen, Chi-Hua', 'Chen, Chun-Chieh', 'Chen, Shiuan-Chih', 'Chou, Ming-Chih', 'Lee, Meng Chih', 'Yen, Ernest Y.T.']",,,,
,PMC,Detection of respiratory pathogens in air samples from acutely infected pigs,,PMC2442681,,,"Pathogens causing significant respiratory disease in growing pigs include Porcine reproductive and respiratory syndrome virus, Porcine circovirus 2, swine influenza virus, porcine respiratory coronavirus, Mycoplasma hyopneumoniae, and Bordetella bronchiseptica. The objective of this research was to characterize the respiratory excretion of these pathogens by acutely infected pigs. Pigs were inoculated under experimental conditions with 1 pathogen. Samples were collected from the upper respiratory tract and exhaled air. All pathogens were detected in swabs of the upper respiratory tract, but only M. hyopneumoniae and B. bronchiseptica were detected in expired air from individually sampled, acutely infected pigs. These findings suggest either that the acutely infected pigs did not aerosolize the viruses or that the quantity of virus excreted was below the detection threshold of current sampling or assay systems, or both, at the individual-pig level.",,"['Hermann, Joseph R.', 'Brockmeier, Susan L.', 'Yoon, Kyoung-Jin', 'Zimmerman, Jeffrey J.']",,,,
,PMC,Development of Broad-Spectrum Halomethyl Ketone Inhibitors Against Coronavirus Main Protease 3CL(pro),http://dx.doi.org/10.1111/j.1747-0285.2008.00679.x,PMC2597651,,,"Coronaviruses comprise a large group of RNA viruses with diverse host specificity. The emergence of highly pathogenic strains like the SARS coronavirus (SARS-CoV), and the discovery of two new coronaviruses, NL-63 and HKU1, corroborates the high rate of mutation and recombination that have enabled them to cross species barriers and infect novel hosts. For that reason, the development of broad-spectrum antivirals that are effective against several members of this family is highly desirable. This goal can be accomplished by designing inhibitors against a target, such as the main protease 3CL(pro) (M(pro)), which is highly conserved among all coronaviruses. Here 3CL(pro) derived from the SARS-CoV was used as the primary target to identify a new class of inhibitors containing a halomethyl ketone warhead. The compounds are highly potent against SARS 3CL(pro) with K(i)'s as low as 300 nM. The crystal structure of the complex of one of the compounds with 3CL(pro) indicates that this inhibitor forms a thioether linkage between the halomethyl carbon of the warhead and the catalytic Cys 145. Furthermore, Structure Activity Relationship (SAR) studies of these compounds have led to the identification of a pharmacophore that accurately defines the essential molecular features required for the high affinity.",,"['Bacha, Usman', 'Barrila, Jennifer', 'Gabelli, Sandra B.', 'Kiso, Yoshiaki', 'Amzel, L. Mario', 'Freire, Ernesto']",,,,
,PMC,Evidence-Based Biosafety: a Review of the Principles and Effectiveness of Microbiological Containment Measures,http://dx.doi.org/10.1128/CMR.00014-08,PMC2493080,,,"We examined the available evidence on the effectiveness of measures aimed at protecting humans and the environment against the risks of working with genetically modified microorganisms (GMOs) and with non-GMO pathogenic microorganisms. A few principles and methods underlie the current biosafety practice: risk assessment, biological containment, concentration and enclosure, exposure minimization, physical containment, and hazard minimization. Many of the current practices are based on experience and expert judgment. The effectiveness of biosafety measures may be evaluated at the level of single containment equipment items and procedures, at the level of the laboratory as a whole, or at the clinical-epidemiological level. Data on the containment effectiveness of equipment and laboratories are scarce and fragmented. Laboratory-acquired infections (LAIs) are therefore important for evaluating the effectiveness of biosafety. For the majority of LAIs there appears to be no direct cause, suggesting that failures of biosafety were not noticed or that containment may have been insufficient. The number of reported laboratory accidents associated with GMOs is substantially lower than that of those associated with non-GMOs. It is unknown to what extent specific measures contribute to the overall level of biosafety. We therefore recommend that the evidence base of biosafety practice be strengthened.",,"['Kimman, Tjeerd G.', 'Smit, Eric', 'Klein, Michèl R.']",,,,
,PMC,Protecting global health security through the International Health Regulations: requirements and challenges,http://dx.doi.org/10.1503/cmaj.080516,PMC2464486,,,,,"['Wilson, Kumanan', 'von Tigerstrom, Barbara', 'McDougall, Christopher']",,,,
,PMC,Antibodies against viruses: passive and active immunization,http://dx.doi.org/10.1016/j.coi.2008.06.005,PMC2730944,,,"Antibodies, through passive or active immunization, play a central role in prophylaxis against many infectious agents. While neutralization is a primary function of antibodies in protection against most viruses, the relative contribution of Fc-dependent and complement-dependent antiviral activities of antibodies was found to vary between different viruses in recent studies. The multiple hit model explains how antibodies neutralize viruses and recent data on the stoichiometry of antibody neutralization suggest that the organization of viral surface proteins on viruses, in addition to virus size, influences the level of antibody occupancy required for neutralization. These new findings will improve our strategies in therapeutic antibody engineering and rational vaccine design.",,"['Law, Mansun', 'Hangartner, Lars']",,,,
,PMC,Pricing infectious disease: The economic and health implications of infectious diseases,http://dx.doi.org/10.1038/embor.2008.110,PMC3327542,,,,,"Fonkwo, Peter Ndeboc",,,,
,PMC,Hematology and Plasma Chemistry Reference Intervals for Mature Laboratory Pine Voles (Microtus pinetorum) as Determined by Using the Nonparametric Rank Percentile Method,,PMC2694717,,,"Plasma biochemical and hematologic values are important parameters for assessing animal health and experimental results. Although normal reference values for many rodent species have been published, there is a dearth of similar information for the genus Microtus. In addition, most studies use a mean and standard deviation to establish reference intervals, but doing so is not the recommendation of the Clinical and Laboratory Standards Institute (formerly the National Committee on Clinical Laboratory Standards) or the International Federation of Clinical Chemistry and Laboratory Medicine. The purpose of this study was to establish normal reference parameters for plasma biochemistry and hematology in mature pine voles (Microtus pinetorum) by using the nonparametric rank percentile method as recommended by the 2 laboratory medicine organizations mentioned. Samples of cardiac blood from a closed colony of pine voles were collected at euthanasia and evaluated under rodent settings on 2 automated hematology analyzers from 2 different manufacturers and on the same type of automated biochemistry analyzer. There were no sex-associated clinically significant differences between the sexes; younger animals had a lower hematocrit, higher mean corpuscular volume, and lower mean corpuscular hemoglobin concentration than did older animals. Only platelet counts differed when comparing hematologic values from different analyzers. Relative to rats and mice, pine voles have a lower mean corpuscular volume and higher red blood cell count, higher blood urea nitrogen, much higher alanine aminotransferase, and lower glucose and phosphorous concentrations. Hematology and plasma biochemical results obtained in this study are considered representative for healthy adult laboratory pine voles under similar environmental conditions.",,"['Harvey, Stephen B', 'Krimer, Paula M', 'Correa, Maria T', 'Hanes, Martha A']",,,,
,PMC,Adverse Effects of Incorporating Ketoprofen into Established Rodent Studies,,PMC2694716,,,"The use of analgesics to prevent or treat postprocedural pain in rodents is increasingly encouraged by the laboratory animal community and federal funding agencies. However, the effects of analgesics on experimental outcomes are not well-documented. In this study, we incorporated ketoprofen into a well-established experimental protocol. Of the 44 Sprague–Dawley (SD) rats obtained from vendor A that were given either ketoprofen (10 mg/kg SC) or saline and underwent ovariectomy, 19 that received ketoprofen died or were euthanized due to clinical illness within 3 to 7 d after surgery. Necropsy revealed gastrointestinal ulceration consistent with toxicity from nonsteroidal antiinflammatory drug. In an attempt to identify factors responsible for this unanticipated outcome, SD rats from vendors A and B were subjected to the same protocol, but no clinical signs or pathologic lesions were observed in any of these rats, regardless of source. A third experiment with rats obtained from vendor A and housed in barriers 1 and 2 was done to clarify the conflicting results and to determine whether response to ketoprofen differed at the barrier level. Three of the 6 rats from barrier 2 that received ketoprofen in the third study had gastrointestinal lesions similar to those observed in the first study, whereas none of the rats from barrier 1 had any lesions. These results suggest that the adverse effects seen after administration of ketoprofen were due to differences between barriers.",,"['Lamon, Tennille K', 'Browder, Elizabeth J', 'Sohrabji, Farida', 'Ihrig, Melanie']",,,,
,PMC,Secondary Acute Anterior Uveitis with Hyphema in a Purpose-bred Kitten,,PMC2694713,,,"The sudden onset of unilateral blepharospasm and hyphema, without evidence of corneal damage, initiated a thorough diagnostic work-up of an 11-wk-old purpose-bred intact male domestic shorthair kitten. Secondary acute anterior uveitis and hyphema were most likely due to trauma within the primary enclosure.",,"['Sorrell, Melanie S', 'Taylor, Karen H', 'Fish, Richard E']",,,,
,PMC,CCR2 MEDIATES CONVENTIONAL DENDRITIC CELL RECRUITMENT AND THE FORMATION OF BRONCHOVASCULAR MONONUCLEAR CELL INFILTRATES IN THE LUNGS OF MICE INFECTED WITH CRYPTOCOCCUS NEOFORMANS,,PMC2735104,,,"Pulmonary clearance of the encapsulated yeast Cryptococcus neoformans requires the development of T1-type immunity. CCR2-deficient mice infected with C. neoformans develop a non-protective T2 immune response and persistent infection. The mechanisms responsible for this aberrant response are unknown. The objective of this study was to define the number, phenotype, and micro-anatomic location of dendritic cells (DC) residing within the lung of CCR2(+/+) or CCR2(−/−) mice throughout a time course following infection with C. neoformans. Results demonstrate the CCR2-mediated recruitment of conventional DC expressing modest amounts of co-stimulatory molecules. DC recruitment was preceded by the up-regulation in the lung of the CCR2 ligands CCL2 and CCL7. Co-localization of numerous DC and CD4(+) T cells within bronchovascular infiltrates coincided with increased expression of IL-12 and IFN-γ. By contrast, in the absence of CCR2, DC recruitment was markedly impaired, bronchovascular infiltrates were diminished, and mice developed features of T2 responses, including bronchovascular collagen deposition and IL-4 production. Our results demonstrate that CCR2 is required for the recruitment of large numbers of conventional DC to bronchovascular infiltrates in mice mounting a T1 immune response against a fungal pathogen. These findings shed new insight into the mechanism(s) by which DC recruitment alters T cell polarization in response to an infectious challenge within the lung.",,"['Osterholzer, John J.', 'Curtis, Jeffrey L.', 'Polak, Timothy', 'Ames, Theresa', 'Chen, Gwo-Hsiao', 'McDonald, Rod', 'Huffnagle, Gary B', 'Toews, Galen B.']",,,,
,PMC,"Biodistribution and Toxicological Safety of Adenovirus Type 5 and Type 35 Vectored Vaccines Against Human Immunodeficiency Virus-1 (HIV-1), Ebola, or Marburg Are Similar Despite Differing Adenovirus Serotype Vector, Manufacturer's Construct, or Gene Inserts",http://dx.doi.org/10.1080/15376510802312464,PMC2777703,,,"The Vaccine Research Center has developed vaccine candidates for different diseases/infectious agents (including HIV-1, Ebola, and Marburg viruses) built on an adenovirus vector platform, based on adenovirus type 5 or 35. To support clinical development of each vaccine candidate, pre-clinical studies were performed in rabbits to determine where in the body they biodistribute and how rapidly they clear, and to screen for potential toxicities (intrinsic and immunotoxicities). The vaccines biodistribute only to spleen, liver (Ad5 only), and/or iliac lymph node (Ad35 only) and otherwise remain in the site of injection muscle and overlying subcutis. Though ∼10(11) viral particles were inoculated, already by Day 9, all but 10(3) to 10(5) genome copies per μg of DNA had cleared from the injection site muscle. By three months, the adenovector was cleared with, at most, a few animals retaining a small number of copies in the injection site, spleen (Ad5), or iliac lymph node (Ad35). This pattern of limited biodistribution and extensive clearance is consistent regardless of differences in adenovector type (Ad5 or 35), manufacturer's construct and production methods, or gene-insert. Repeated dose toxicology studies identified treatment-related toxicities confined primarily to the sites of injection, in certain clinical pathology parameters, and in body temperatures (Ad5 vectors) and food consumption immediately post-inoculation. Systemic reactogenicity and reactogenicity at the sites of injection demonstrated reversibility. These data demonstrate the safety and suitability for investigational human use of Ad5 or Ad35 adenovector-based vaccine candidates at doses of up to 2 × 10(11) given intramuscularly to prevent various infectious diseases.",,"['Sheets, Rebecca L.', 'Stein, Judith', 'Bailer, Robert T.', 'Koup, Richard A.', 'Andrews, Charla', 'Nason, Martha', 'He, Bin', 'Koo, Edward', 'Trotter, Holly', 'Duffy, Chris', 'Manetz, T. Scott', 'Gomez, Phillip']",,,,
,PMC,Seoul virus enhances regulatory and reduces proinflammatory responses in male Norway rats,http://dx.doi.org/10.1002/jmv.21213,PMC4145243,,,"Zoonotic pathogens, including hantaviruses, are maintained in the environment by causing persistent infection in the absence of disease in their reservoir hosts. Spillover of hantaviruses to humans can cause severe disease that is mediated by excessive proinflammatory responses. The mechanisms mediating hantaviral persistence in rodent reservoirs remain largely unknown. Male Norway rats were inoculated with their species-specific hantavirus, Seoul virus (SEOV), and viral RNA, cytokine, and chemokine responses were evaluated in spleen and lung tissue. More viral RNA was detectable in the lungs than spleen, with copies of SEOV peaking 15-30 days post-inoculation (p.i.) and persisting for 60 days p.i. In the lungs, the expression and production of proinflammatory mediators (i.e. IL-1β, IL-6, TNF-α, IFN-γ, CCL5, CCL2, CX3CL1, CXCL10, VCAM, VEGF, and NOS2) remained at or below baseline throughout SEOV infection; whereas, regulatory factors, including TGF-β and FoxP3 were elevated. Conversely, in the spleen, proinflammatory responses were induced while regulatory responses remained unchanged during infection. To determine whether reduced proinflammatory responses mediate hantavirus persistence in the lungs, male rats were administered rIL-1β or vehicle for 30 days during SEOV infection. SEOV persistence and shedding were not affected by IL-1β treatment. Proinflammatory responses were elevated in rIL-1β-treated rats, but remained within physiological levels, suggesting that supra-physiological concentrations may be necessary for viral clearance at the cost of causing disease. Elevated regulatory responses may suppress excessively high proinflammatory responses at a site of elevated SEOV replication to contribute to viral persistence and prevent proinflammatory-mediated disease in reservoir hosts.",,"['Easterbrook, Judith D.', 'Klein, Sabra L.']",,,,
,PMC,Comparison of Automated Nucleic Acid Extraction Methods with Manual Extraction,http://dx.doi.org/10.2353/jmoldx.2008.070149,PMC2438199,,,"Automated nucleic acid extractors can improve workflow and decrease variability in the clinical laboratory. We evaluated Qiagen EZ1 (Valencia, CA) and bioMérieux (Durham, NC) easyMAG extractors compared with Qiagen manual extraction using targets and matrices commonly available in the clinical laboratory. Pooled samples were spiked with various organisms, serially diluted, and extracted in duplicate. The organisms/matrices were Bordetella pertussis/bronchoalveolar lavage, herpes simplex virus II/cerebrospinal fluid, coxsackievirus A9/cerebrospinal fluid, BK virus/plasma, and Mycoplasma pneumoniae/endotracheal tube samples. Extracts were amplified in duplicate using real-time PCR assays, and amplification of the target at a cycle threshold of 35 using the manual method was used for comparison. Amplification efficiency of nucleic acids extracted by automated methods was similar to that by the manual method except for a loss of efficiency for M. pneumoniae in endotracheal tube samples. The EZ1 viral kit 2.0 gave better results for coxsackievirus A9 than the EZ1 viral kit version 1.0. At the lowest limit of detection (past a cycle threshold of 35), the easyMAG was more likely to produce amplifiable nucleic acid than were either the EZ1 or manual extraction. Operational complexity, defined as the number of manipulations required to obtain an extracted sample, was the lowest for the easyMAG. The easyMAG was the most expensive of the methods, followed by the EZ1 kit and manual extraction.",,"['Dundas, Nicola', 'Leos, N. Kristine', 'Mitui, Midori', 'Revell, Paula', 'Rogers, Beverly Barton']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.01084-08,PMC2446987,,,,,,,,,
,PMC,Ocelots on Barro Colorado Island Are Infected with Feline Immunodeficiency Virus but Not Other Common Feline and Canine Viruses,,PMC3169092,,,"Transmission of pathogens from domestic animals to wildlife populations (spill-over) has precipitated local wildlife extinctions in multiple geographic locations. Identifying such events before they cause population declines requires differentiating spillover from endemic disease, a challenge complicated by a lack of baseline data from wildlife populations that are isolated from domestic animals. We tested sera collected from 12 ocelots (Leopardus pardalis) native to Barro Colorado Island, Panama, which is free of domestic animals, for antibodies to feline herpes virus, feline calicivirus, feline corona virus, feline panleukopenia virus, canine distemper virus, and feline immunodeficiency virus (FIV), typically a species-specific infection. Samples also were tested for feline leukemia virus antigens. Positive tests results were only observed for FIV; 50% of the ocelots were positive. We hypothesize that isolation of this population has prevented introduction of pathogens typically attributed to contact with domestic animals. The high density of ocelots on Barro Colorado Island may contribute to a high prevalence of FIV infection, as would be expected with increased contact rates among conspecifics in a geographically restricted population.",,"['Franklin, Samuel P.', 'Kays, Roland W.', 'Moreno, Ricardo', 'TerWee, Julie A.', 'Troyer, Jennifer L.', 'VandeWoude, Sue']",,,,
,PMC,Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections,http://dx.doi.org/10.1038/nri2318,PMC5573867,,,"A diverse and well-balanced repertoire of T cells is believed to be crucial for the efficacious defence against infection with new or re-emerging pathogens throughout life. In the last third of the mammalian lifespan, the maintenance of a balanced T-cell repertoire becomes highly challenging due to changes in T-cell production and consumption. In this Review, I ask whether latent persistent pathogens might be key factors that drive this imbalance and whether they determine the extent of age-associated immune deficiency",,"Nikolich-Žugich, Janko",,,,
,PMC,Interferon-inducible antiviral effectors,http://dx.doi.org/10.1038/nri2314,PMC2522268,,,"Since the discovery of interferons (IFNs), considerable progress has been made in describing the nature of the cytokines themselves, the signalling components that direct the cell response and their antiviral activities. Gene targeting studies have distinguished four effector pathways of the IFN-mediated antiviral response: the Mx GTPase pathway, the 2′-5′ oligoadenylate-synthetase-directed ribonuclease L pathway, the protein kinase R pathway and the ISG15 ubiquitin-like pathway. These effector pathways individually block viral transcription, degrade viral RNA, inhibit translation, and modify protein function to control all steps of viral replication. Ongoing research continues to expose additional activities for the effector proteins and has revealed unanticipated functions of the antiviral response.",,"['Sadler, Anthony J.', 'Williams, Bryan R. G.']",,,,
,PMC,"Regionalization in Local Public Health Systems: Variation in Rationale, Implementation, and Impact on Public Health Preparedness",,PMC2430640,,,"Comparative case studies found that regionalization originated from a crisis or perceived need for a coordinated response, a need to build local public health capacity, or an effort to use federal preparedness funds more efficiently. Regions vary in terms of their congruence with regional structures for partner agencies, such as emergency management agencies, as well as hospital and health services markets and organizational structure. Some focus on building formal organizational relationships to coordinate and sometimes standardize preparedness and response activities or build regional capacity, while others focus on building informal professional networks. Whatever the approach, strong leadership and trust are required for effective planning, emergency response, and sustainability. This article suggests that regionalization improves emergency preparedness by allowing for more efficient use of resources and better coordination and demonstrated progress in terms of planning and coordination; regional capacity-building, training, and exercises; and development of professional networks.",,"Stoto, Michael A.",,,,
,PMC,The stimulatory RNA of the Visna-Maedi retrovirus ribosomal frameshifting signal is an unusual pseudoknot with an interstem element,http://dx.doi.org/10.1261/rna.1042108,PMC2441976,,,"The stimulatory RNA of the Visna-Maedi virus (VMV) −1 ribosomal frameshifting signal has not previously been characterized but can be modeled either as a two-stem helix, reminiscent of the HIV-1 frameshift-stimulatory RNA, or as an RNA pseudoknot. The pseudoknot is unusual in that it would include a 7 nucleotide loop (termed here an interstem element [ISE]) between the two stems. In almost all frameshift-promoting pseudoknots, ISEs are absent or comprise a single adenosine residue. Using a combination of RNA structure probing, site directed mutagenesis, NMR, and phylogenetic sequence comparisons, we show here that the VMV stimulatory RNA is indeed a pseudoknot, conforming closely to the modeled structure, and that the ISE is essential for frameshifting. Pseudoknot function was predictably sensitive to changes in the length of the ISE, yet altering its sequence to alternate pyrimidine/purine bases was also detrimental to frameshifting, perhaps through modulation of local tertiary interactions. How the ISE is placed in the context of an appropriate helical junction conformation is not known, but its presence impacts on other elements of the pseudoknot, for example, the necessity for a longer than expected loop 1. This may be required to accommodate an increased flexibility of the pseudoknot brought about by the ISE. In support of this, (1)H NMR analysis at increasing temperatures revealed that stem 2 of the VMV pseudoknot is more labile than stem 1, perhaps as a consequence of its connection to stem 1 solely via flexible single-stranded loops.",,"['Pennell, Simon', 'Manktelow, Emily', 'Flatt, Andrew', 'Kelly, Geoff', 'Smerdon, Stephen J.', 'Brierley, Ian']",,,,
,PMC,Long-Term Care Facilities: A Cornucopia of Viral Pathogens,http://dx.doi.org/10.1111/j.1532-5415.2008.01775.x,PMC2875942,,,"OBJECTIVES: To determine the frequency and types of respiratory viruses circulating in Boston long-term care facilities (LTCFs) during a 3-year period. DESIGN: Observational. SETTING: Thirty-three Boston-area LTCFs over a 3-year period. PARTICIPANTS: Residents of long-term care who had previously participated in a trial of vitamin E supplementation and had paired serum samples available for viral analysis. MEASUREMENTS: Viral antibody titers to eight respiratory viruses (influenza A and B, respiratory syncytial virus (RSV), parainfluenza virus serotype three (PIV-3), PIV-2, human metapneumovirus (hMPV), and coronaviruses 229E and OC43) were measured using enzyme immunoassay at baseline and 53 weeks. Infection was defined as a more than quadrupling of viral titers. Clinical data on respiratory illnesses were collected throughout the study period. RESULTS: A total of 617 persons were enrolled in the trial. Of these, 382 (62%) had sera available for viral analysis. A total of 204 viral infections were documented in 157 subjects. Serological responses to all eight viruses were documented, with hMPV (12.8%) and coronavirus 229E (10.5%) being the most common and PIV-2 (2.4%) the least common. The occurrence of bronchitis (P = .007), pneumonia (P = .02), and any lower respiratory tract infection (P = .002) was significantly associated with having a viral diagnosis. CONCLUSION: A wide range of respiratory viruses cocirculates in LTCFs and contributes to respiratory illness morbidity in these populations.",,"['Falsey, Ann R.', 'Dallal, Gerard E.', 'Formica, Maria A.', 'Andolina, Gloria G.', 'Hamer, Davidson H.', 'Leka, Lynette L.', 'Meydani, Simin Nikbin']",,,,
,PMC,Sensitive and Broadly Reactive Reverse Transcription-PCR Assays To Detect Novel Paramyxoviruses,http://dx.doi.org/10.1128/JCM.00192-08,PMC2519498,,,"We have developed a set of reverse transcription-PCR assays for the detection and identification of known and novel paramyxoviruses in clinical specimens. Primers were designed from the conserved motifs of the polymerase pol gene sequences to detect members of the Paramyxovirinae or Pneumovirinae subfamily or groups of genera within the Paramyxovirinae subfamily. The consensus-degenerate hybrid oligonucleotide primer design and seminested or nested PCR assay design were used to enhance the breadth of reactivity and sensitivity of the respective assays. Using expressed RNA and 10-fold dilution series of virus-infected tissue culture isolates from different members of the family or genera, these assays were able to detect on average between 100 and 500 copies of template RNA. The assays were specific to the respective group of genera or subfamily viruses. This set of primers enhances our ability to look for novel viruses in outbreaks and diseases of unknown etiology.",,"['Tong, Suxiang', 'Chern, Shur-Wern Wang', 'Li, Yan', 'Pallansch, Mark A.', 'Anderson, Larry J.']",,,,
,PMC,CD81 Is a Central Regulator of Cellular Events Required for Hepatitis C Virus Infection of Human Hepatocytes,http://dx.doi.org/10.1128/JVI.00665-08,PMC2519688,,,"Infection with hepatitis C virus (HCV) is still a major public health problem, and the events leading to hepatocyte infection are not yet fully understood. Combining confocal microscopy with biochemical analysis and studies of infection requirements using pharmacological inhibitors and small interfering RNAs, we show here that engagement of CD81 activates the Rho GTPase family members Rac, Rho, and Cdc42 and that the block of these signaling pathways drastically reduces HCV infectivity. Activation of Rho GTPases mediates actin-dependent relocalization of the HCV E2/CD81 complex to cell-cell contact areas where CD81 comes into contact with the tight-junction proteins occludin, ZO-1, and claudin-1, which was recently described as an HCV coreceptor. Finally, we show that CD81 engagement activates the Raf/MEK/ERK signaling cascade and that this pathway affects postentry events of the virus life cycle. In conclusion, we describe a range of cellular events that are manipulated by HCV to coordinate interactions with its multiple coreceptors and to establish productive infections and find that CD81 is a central regulator of these events.",,"['Brazzoli, Michela', 'Bianchi, Alessia', 'Filippini, Sara', 'Weiner, Amy', 'Zhu, Qing', 'Pizza, Mariagrazia', 'Crotta, Stefania']",,,,
,PMC,Experimental Optic Neuritis Induced by a Demyelinating Strain of Mouse Hepatitis Virus,http://dx.doi.org/10.1128/JVI.00920-08,PMC2519666,,,"Optic neuritis (ON), an inflammatory demyelinating optic nerve disease, occurs in multiple sclerosis (MS). Pathological mechanisms and potential treatments for ON have been studied via experimental autoimmune MS models. However, evidence suggests that virus-induced inflammation is a likely etiology triggering MS and ON; experimental virus-induced ON models are therefore required. We demonstrate that MHV-A59, a mouse hepatitis virus (MHV) strain that causes brain and spinal cord inflammation and demyelination, induces ON by promoting mixed inflammatory cell infiltration. In contrast, MHV-2, a nondemyelinating MHV strain, does not induce ON. Results reveal a reproducible virus-induced ON model important for the evaluation of novel therapies.",,"['Shindler, Kenneth S.', 'Kenyon, Lawrence C.', 'Dutt, Mahasweta', 'Hingley, Susan T.', 'Sarma, Jayasri Das']",,,,
,PMC,Pathways of Cross-Species Transmission of Synthetically Reconstructed Zoonotic Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.00818-08,PMC2519660,,,"Zoonotic severe acute respiratory syndrome coronavirus (SARS-CoV) likely evolved to infect humans by a series of transmission events between humans and animals in markets in China. Virus sequence data suggest that the palm civet served as an amplification host in which civet and human interaction fostered the evolution of the epidemic SARS Urbani strain. The prototypic civet strain of SARS-CoV, SZ16, was isolated from a palm civet but has not been successfully cultured in vitro. To propagate a chimeric recombinant SARS-CoV bearing an SZ16 spike (S) glycoprotein (icSZ16-S), we constructed cell lines expressing the civet ortholog (DBT-cACE2) of the SARS-CoV receptor (hACE2). Zoonotic SARS-CoV was completely dependent on ACE2 for entry. Urbani grew with similar kinetics in both the DBT-cACE2 and the DBT-hACE2 cells, while icSZ16-S only grew in DBT-cACE2 cells. The SZ16-S mutant viruses adapted to human airway epithelial cells and displayed enhanced affinity for hACE2 but exhibited severe growth defects in the DBT-cACE2 cells, suggesting that the evolutionary pathway that promoted efficient hACE2 interactions simultaneously abolished efficient cACE2 interactions. Structural modeling predicted two distinct biochemical interaction networks by which zoonotic receptor binding domain architecture can productively engage hACE2, but only the Urbani mutational repertoire promoted efficient usage of both hACE2 and cACE2 binding interfaces. Since dual species tropism was preserved in Urbani, it is likely that the virus evolved a high affinity for cACE2/hACE2 receptors through adaptation via repeated passages between human and civet hosts. Furthermore, zoonotic SARS-CoV was variably neutralized by antibodies that were effective against the epidemic strain, highlighting their utility for evaluating passive immunization efficacy.",,"['Sheahan, Timothy', 'Rockx, Barry', 'Donaldson, Eric', 'Corti, Davide', 'Baric, Ralph']",,,,
,PMC,Persistent Equine Arteritis Virus Infection in HeLa Cells,http://dx.doi.org/10.1128/JVI.01249-08,PMC2519626,,,"The horse-adapted virulent Bucyrus (VB) strain of equine arteritis virus (EAV) established persistent infection in high-passage-number human cervix cells (HeLa-H cells; passages 170 to 221) but not in low-passage-number human cervix cells (HeLa-L cells; passages 95 to 115) or in several other cell lines that were evaluated. However, virus recovered from the 80th passage of the persistently infected HeLa-H cells (HeLa-H-EAVP80) readily established persistent infection in HeLa-L cells. Comparative sequence analysis of the entire genomes of the VB and HeLa-H-EAVP80 viruses identified 16 amino acid substitutions, including 4 in the replicase (nsp1, nsp2, nsp7, and nsp9) and 12 in the structural proteins (E, GP2, GP3, GP4, and GP5). Reverse genetic studies clearly showed that substitutions in the structural proteins but not the replicase were responsible for the establishment of persistent infection in HeLa-L cells by the HeLa-H-EAVP80 virus. It was further demonstrated that recombinant viruses with substitutions in the minor structural proteins E and GP2 or GP3 and GP4 were unable to establish persistent infection in HeLa-L cells but that recombinant viruses with combined substitutions in the E (Ser53→Cys and Val55→Ala), GP2 (Leu15→Ser, Trp31→Arg, Val87→Leu, and Ala112→Thr), GP3 (Ser115→Gly and Leu135→Pro), and GP4 (Tyr4→His and Ile109→Phe) proteins or with a single point mutation in the GP5 protein (Pro98→Leu) were able to establish persistent infection in HeLa-L cells. In summary, an in vitro model of EAV persistence in cell culture was established for the first time. This system can provide a valuable model for studying virus-host cell interactions, especially virus-receptor interactions.",,"['Zhang, Jianqiang', 'Timoney, Peter J.', 'MacLachlan, N. James', 'McCollum, William H.', 'Balasuriya, Udeni B. R.']",,,,
,PMC,Comprehensive analysis of T cell epitope discovery strategies using 17DD yellow 2 fever virus structural proteins and BALB/c (H2(d)) mice model,http://dx.doi.org/10.1016/j.virol.2008.04.043,PMC2615555,,,"Immunomics research uses in silico epitope prediction, as well as in vivo and in vitro approaches. We inoculated BALB/c (H2(d)) mice with 17DD yellow fever vaccine to investigate the correlations between approaches used for epitope discovery: ELISPOT assays, binding assays, and prediction software. Our results showed a good agreement between ELISPOT and binding assays, which seemed to correlate with the protein immunogenicity. PRED(BALB/c) prediction software partially agreed with the ELISPOT and binding assay results, but presented low specificity. The use of prediction software to exclude peptides containing no epitopes, followed by high throughput screening of the remaining peptides by ELISPOT, and the use of MHC-biding assays to characterize the MHC restrictions demonstrated to be an efficient strategy. The results allowed the characterization of 2 MHC class I and 17 class II epitopes in the envelope protein of the YF virus in BALB/c (H2(d)) mice.",,"['Junior, Milton Maciel', 'Kellathur, Srinivasan N.', 'Chikhlikar, Pryia', 'Dhalia, Rafael', 'Sidney, John', 'Sette, Alessandro', 'August, Thomas J.', 'Marques, Ernesto T. A.']",,,,
,PMC,Viral destruction of cell surface receptors,http://dx.doi.org/10.1073/pnas.0804355105,PMC2449321,,,,,"['Mesecar, Andrew D.', 'Ratia, Kiira']",,,,
,PMC,Cathepsin L Functionally Cleaves the Severe Acute Respiratory Syndrome Coronavirus Class I Fusion Protein Upstream of Rather than Adjacent to the Fusion Peptide,http://dx.doi.org/10.1128/JVI.00415-08,PMC2519682,,,"Unlike other class I viral fusion proteins, spike proteins on severe acute respiratory sydrome coronavirus virions are uncleaved. As we and others have demonstrated, infection by this virus depends on cathepsin proteases present in endosomal compartments of the target cell, suggesting that the spike protein acquires its fusion competence by cleavage during cell entry rather than during virion biogenesis. Here we demonstrate that cathepsin L indeed activates the membrane fusion function of the spike protein. Moreover, cleavage was mapped to the same region where, in coronaviruses carrying furin-activated spikes, the receptor binding subunit of the protein is separated from the membrane-anchored fusion subunit.",,"['Bosch, Berend Jan', 'Bartelink, Willem', 'Rottier, Peter J. M.']",,,,
,PMC,"Structure of the Main Protease from a Global Infectious Human Coronavirus, HCoV-HKU1",http://dx.doi.org/10.1128/JVI.00298-08,PMC2519634,,,"The newly emergent human coronavirus HKU1 (HCoV-HKU1) was first identified in Hong Kong in 2005. Infection by HCoV-HKU1 occurs worldwide and causes syndromes such as the common cold, bronchitis, and pneumonia. The CoV main protease (M(pro)), which is a key enzyme in viral replication via the proteolytic processing of the replicase polyproteins, has been recognized as an attractive target for rational drug design. In this study, we report the structure of HCoV-HKU1 M(pro) in complex with a Michael acceptor, inhibitor N3. The structure of HCoV-HKU1 provides a high-quality model for group 2A CoVs, which are distinct from group 2B CoVs such as severe acute respiratory syndrome CoV. The structure, together with activity assays, supports the relative conservation at the P1 position that was discovered by sequencing the HCoV-HKU1 genome. Combined with structural data from other CoV M(pro)s, the HCoV-HKU1 M(pro) structure reported here provides insights into both substrate preference and the design of antivirals targeting CoVs.",,"['Zhao, Qi', 'Li, Shuang', 'Xue, Fei', 'Zou, Yilong', 'Chen, Cheng', 'Bartlam, Mark', 'Rao, Zihe']",,,,
,PMC,Emodin is a novel alkaline nuclease inhibitor that suppresses herpes simplex virus type 1 yields in cell cultures,http://dx.doi.org/10.1038/bjp.2008.242,PMC2538697,,,"BACKGROUND AND PURPOSE: Most antiviral therapies directed against herpes simplex virus (HSV) infections are limited to a small group of nucleoside analogues that target the viral polymerase. Extensive clinical use of these drugs has led to the emergence of resistant viral strains, mainly in immunocompromised patients. This highlights the need for the development of new anti-herpesviral drugs with novel targets. Herein the effects of a plant anthraquinone, emodin, on the HSV-1 alkaline nuclease activity and virus yields were investigated. EXPERIMENTAL APPROACH: HSV-1 alkaline nuclease activity was examined by nuclease activity assay. Inhibition of virus yields was measured by plaque reduction assay and immunohistochemical staining. Interaction between emodin and alkaline nuclease was analysed by docking technology. KEY RESULTS: Emodin specifically inhibited the nuclease activity of HSV-1 UL12 alkaline nuclease in a biochemical assay. Plaque reduction assay revealed that emodin reduced the plaque formation with an EC(50) of 21.5±4.4 μM. Immunohistochemical staining using the anti-nucleocapsid protein antibody demonstrated that emodin induced the accumulation of viral nucleocapsids in the nucleus in a dose-dependent manner. Docking analysis further suggested that the inhibitory effect of emodin on the UL12 activity may result from the interaction between emodin and critical catalytic amino acid residues of UL12. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that emodin is a potent anti-HSV agent that inhibits the yields of HSV-1 via the suppression of a novel target, UL12.",,"['Hsiang, C-Y', 'Ho, T-Y']",,,,
,PMC,"Neuroimmunology of central nervous system viral infections: the cells, molecules and mechanisms involved",http://dx.doi.org/10.1016/j.coph.2008.05.002,PMC2613975,,,"Viral infections of the central nervous system (CNS) necessitate rapid, yet tightly controlled responses to contain viral spread while limiting tissue damage. All CNS resident cell types are equipped with pattern recognition receptors (PRRs) to respond to viruses. The resulting activation of IFN-α/β, proinflammatory cytokines and chemokines is dependent on the virus replication strategy, tropism and PRR distribution. Although IFN-α/β induced antiviral mediators are essential to restrict initial viral spread, adaptive immunity promoted by chemokines, cytokines and metalloproteinases is equally critical in lowering viral burden. Recognition of viral antigen presented by MHC molecules is critical for T cell retention and function. Non lytic clearance mechanisms mediated by IFN-γ and antibodies prevail in providing protection. Targeted intervention can be achieved by PRR stimulation, chemokine-receptor blockade and immune modulation of T cell function. However, due to the extensive positive and negative feedback signaling cascades linking innate and adaptive immune responses, enhanced anti-viral functions will have to be counterbalanced to avoid pathology.",,"['Savarin, Carine', 'Bergmann, Cornelia C.']",,,,
,PMC,Modulation of influenza virus replication by alteration of sodium ion transport and protein kinase C activity,http://dx.doi.org/10.1016/j.antiviral.2008.05.008,PMC2614658,,,"In recent years, increasing levels of resistance to the four FDA-approved anti-influenza virus drugs have been described and vaccine manufacturers have experienced demands that exceed their capacity. This situation underlines the urgent need for novel antivirals as well as innovations in vaccine production in preparation for the next influenza epidemic. Here we report the development of a cell-based high-throughput screen which we have used for the identification of compounds that modulate influenza virus growth either negatively or positively. We screened a library of compounds with known biological activity and identified distinct groups of inhibitors and enhancers that target sodium channels or protein kinase C (PKC). We confirmed these results in viral growth assays and find that treatment with a sodium channel opener or PKC inhibitor significantly reduces viral replication. In contrast, inhibition of sodium channels or activation of PKC leads to enhanced virus production in tissue culture. These diametrically opposing effects strongly support a role for PKC activity and the regulation of Na(+) currents in influenza virus replication and both may serve as targets for antiviral drugs. Furthermore, we raise the possibility that compounds that result in increased viral titers may be beneficial for boosting the production of tissue culture-grown influenza vaccines.",,"['Hoffmann, H.-Heinrich', 'Palese, Peter', 'Shaw, Megan L.']",,,,
,PMC,Novel Astroviruses in Insectivorous Bats,http://dx.doi.org/10.1128/JVI.00857-08,PMC2546893,,,"Bats are increasingly recognized to harbor a wide range of viruses, and in most instances these viruses appear to establish long-term persistence in these animals. They are the reservoir of a number of human zoonotic diseases including Nipah, Ebola, and severe acute respiratory syndrome. We report the identification of novel groups of astroviruses in apparently healthy insectivorous bats found in Hong Kong, in particular, bats belonging to the genera Miniopterus and Myotis. Astroviruses are important causes of diarrhea in many animal species, including humans. Many of the bat astroviruses form distinct phylogenetic clusters in the genus Mamastrovirus within the family Astroviridae. Virus detection rates of 36% to 100% and 50% to 70% were found in Miniopterus magnater and Miniopterus pusillus bats, respectively, captured within a single bat habitat during four consecutive visits spanning 1 year. There was high genetic diversity of viruses in bats found within this single habitat. Some bat astroviruses may be phylogenetically related to human astroviruses, and further studies with a wider range of bat species in different geographic locations are warranted. These findings are likely to provide new insights into the ecology and evolution of astroviruses and reinforce the role of bats as a reservoir of viruses with potential to pose a zoonotic threat to human health.",,"['Chu, D. K. W.', 'Poon, L. L. M.', 'Guan, Y.', 'Peiris, J. S. M.']",,,,
,PMC,Human Parvovirus B19 NS1 Protein Modulates Inflammatory Signaling by Activation of STAT3/PIAS3 in Human Endothelial Cells,http://dx.doi.org/10.1128/JVI.00891-08,PMC2519586,,,"The pathogenic mechanism by which parvovirus B19 may induce inflammatory cardiomyopathy (iCMP) is complex but is known to involve inflammatory processes, possibly including activation of JAK/STAT signaling. The nonstructural B19 protein NS1 acts as a transactivator triggering signaling cascades that eventually lead to activation of interleukin 6 (IL-6). We examined the impact of NS1 on modulation of STAT signaling in human endothelial cells (HMEC-1). The NS1 sequences were identified from B19 DNA isolated from the myocardia of patients with fatal iCMP. B19 infection as well as NS1 overexpression in HMEC-1 cells produced a significant upregulation in the phosphorylation of both tyrosine(705) and serine(727) STAT3 (P < 0.05). The increased STAT3 phosphorylation was accompanied by dimerization, nuclear translocation, and DNA binding of pSTAT3. In contrast, NS1 expression did not result in increased STAT1 activation. Notably, the expression levels of the negative regulators of STAT activation, SOCS1 and SOCS3, were not altered by NS1. However, the level of PIAS3 was upregulated in NS1-expressing HMEC-1 cells. Analysis of the transcriptional activation of target genes revealed that NS1-induced STAT3 signaling was associated with upregulation of genes involved in immune response (e.g., the IFNAR1 and IL-2 genes) and downregulation of genes associated with viral defense (e.g., the OAS1 and TYK2 genes). Our results demonstrate that B19 NS1 modulates the STAT/PIAS pathway. The NS1-induced upregulation of STAT3/PIAS3 in the absence of STAT1 phosphorylation and the lack of SOCS1/SOCS3 activation may contribute to the mechanisms by which B19 evades the immune response and establishes persistent infection in human endothelial cells. Thus, NS1 may play a critical role in the mechanism of viral pathogenesis in B19-associated iCMP.",,"['Duechting, Anja', 'Tschöpe, Carsten', 'Kaiser, Heike', 'Lamkemeyer, Tobias', 'Tanaka, Nobuyuki', 'Aberle, Susanne', 'Lang, Florian', 'Torresi, Joseph', 'Kandolf, Reinhard', 'Bock, C.-Thomas']",,,,
,PMC,Mouse Hepatitis Virus Type 2 Enters Cells through a Clathrin-Mediated Endocytic Pathway Independent of Eps15,http://dx.doi.org/10.1128/JVI.00837-08,PMC2519582,,,"It has recently been shown that cell entry of mouse hepatitis virus type 2 (MHV-2) is mediated through endocytosis (Z. Qiu et al., J. Virol. 80:5768-5776, 2006). However, the molecular mechanism underlying MHV-2 entry is not known. Here we employed multiple chemical and molecular approaches to determine the molecular pathways for MHV-2 entry. Our results showed that MHV-2 gene expression and infectivity were significantly inhibited when cells were treated with chemical and physiologic blockers of the clathrin-mediated pathway, such as chlorpromazine and hypertonic sucrose medium. Furthermore, viral gene expression was significantly inhibited when cells were transfected with a small interfering RNA specific to the clathrin heavy chain. However, these treatments did not affect the infectivity and gene expression of MHV-A59, demonstrating the specificity of the inhibitions. In addition, overexpression of a dominant-negative mutant of caveolin 1 did not have any effect on MHV-2 infection, while it significantly blocked the caveolin-dependent uptake of cholera toxin subunit B. These results demonstrate that MHV-2 utilizes the clathrin- but not caveolin-mediated endocytic pathway for entry. Interestingly, when the cells transiently overexpressed a dominant-negative form (DIII) of Eps15, which is thought to be an essential component of the clathrin pathway, viral gene expression and infectivity were unaffected, although DIII expression blocked transferrin uptake and vesicular stomatitis virus infection, which are dependent on clathrin-mediated endocytosis. Thus, MHV-2 entry is mediated through clathrin-dependent but Eps15-independent endocytosis.",,"['Pu, Yinghui', 'Zhang, Xuming']",,,,
,PMC,Effective Chemokine Secretion by Dendritic Cells and Expansion of Cross-Presenting CD4(−)/CD8(+) Dendritic Cells Define a Protective Phenotype in the Mouse Model of Coxsackievirus Myocarditis,http://dx.doi.org/10.1128/JVI.00047-08,PMC2519575,,,"Enteroviruses such as coxsackievirus B3 (CVB3) are able to induce lethal acute and chronic myocarditis. In resistant C57BL/6 mice, CVB3 myocarditis is abrogated by T-cell-dependent mechanisms, whereas major histocompatibility complex (MHC)-matched permissive A.BY/SnJ mice develop chronic myocarditis based on virus persistence. To define the role of T-cell-priming dendritic cells (DCs) in the outcome of CVB3 myocarditis, DCs were analyzed in this animal model in the course of CVB3 infection. In both mouse strains, DCs were found to be infectible with CVB3; however, formation of infectious virions was impaired. In DCs derived from C57BL/6 mice, significantly higher quantities of interleukin-10 (IL-10) and the proinflammatory cytokines IL-6 and tumor necrosis factor alpha were measured compared to those from A.BY/SnJ mice. Additionally, the chemokines interferon-inducible protein 10 (IP-10) and RANTES were secreted by DCs from resistant C57BL/6 mice earlier in infection and at significantly higher levels. The protective role of IP-10 in CVB3 myocarditis was confirmed in IP-10(−/−) mice, which had increased myocardial injury compared to the immunocompetent control animals. Also, major differences in resistant and permissive mice were found in DC subsets, with C57BL/6 mice harboring more cross-priming CD4(−) CD8(+) DCs. As CD4(−) CD8(+) DCs are known to express 10 times more Toll-like receptor 3 (TLR3) than other DC subsets, we followed the course of CVB3 infection in TLR3(−/−) mice. These mice developed a fulminant acute myocarditis and secreted sustained low amounts of type I interferons; secretion of IP-10 and RANTES was nearly abrogated in DCs. We conclude that MHC-independent genetic factors involving DC-related IP-10 secretion and TLR3 expression are beneficial in the prevention of chronic coxsackievirus myocarditis.",,"['Weinzierl, Andreas Oliver', 'Szalay, Gudrun', 'Wolburg, Hartwig', 'Sauter, Martina', 'Rammensee, Hans-Georg', 'Kandolf, Reinhard', 'Stevanović, Stefan', 'Klingel, Karin']",,,,
,PMC,Structural Insights into Calicivirus Attachment and Uncoating,http://dx.doi.org/10.1128/JVI.00550-08,PMC2519574,,,"The Caliciviridae family comprises positive-sense RNA viruses of medical and veterinary significance. In humans, caliciviruses are a major cause of acute gastroenteritis, while in animals respiratory illness, conjunctivitis, stomatitis, and hemorrhagic disease are documented. Investigation of virus-host interactions is limited by a lack of culture systems for many viruses in this family. Feline calicivirus (FCV), a member of the Vesivirus genus, provides a tractable model, since it may be propagated in cell culture. Feline junctional adhesion molecule 1 (fJAM-1) was recently identified as a functional receptor for FCV. We have analyzed the structure of this virus-receptor complex by cryo-electron microscopy and three-dimensional image reconstruction, combined with fitting of homology modeled high-resolution coordinates. We show that domain 1 of fJAM-1 binds to the outer face of the P2 domain of the FCV capsid protein VP1, inducing conformational changes in the viral capsid. This study provides the first structural view of a native calicivirus-protein receptor complex and insights into the mechanisms of virus attachment and uncoating.",,"['Bhella, David', 'Gatherer, Derek', 'Chaudhry, Yasmin', 'Pink, Rebecca', 'Goodfellow, Ian G.']",,,,
,PMC,Functional Characterization of the Cleavage Specificity of the Sapovirus Chymotrypsin-Like Protease,http://dx.doi.org/10.1128/JVI.00693-08,PMC2519560,,,"Sapovirus is a positive-stranded RNA virus with a translational strategy based on processing of a polyprotein precursor by a chymotrypsin-like protease. So far, the molecular mechanisms regulating cleavage specificity of the viral protease are poorly understood. In this study, the catalytic activities and substrate specificities of the predicted forms of the viral protease, the 3C-like protease (NS6) and the 3CD-like protease-polymerase (NS6-7), were examined in vitro. The purified NS6 and NS6-7 were able to cleave synthetic peptides (15 to 17 residues) displaying the cleavage sites of the sapovirus polyprotein, both NS6 and NS6-7 proteins being active forms of the viral protease. High-performance liquid chromatography and subsequent mass spectrometry analysis of digested products showed a specific trans cleavage of peptides bearing Gln-Gly, Gln-Ala, Glu-Gly, Glu-Pro, or Glu-Lys at the scissile bond. In contrast, peptides bearing Glu-Ala or Gln-Asp at the scissile bond (NS4-NS5 and NS5-NS6, or NS6-NS7 junctions, respectively) were resistant to trans cleavage by NS6 or NS6-7 proteins, whereas cis cleavage of the Glu-Ala scissile bond of the NS5-NS6 junction was evidenced. Interestingly, the presence of a Phe at position P4 overruled the resistance to trans cleavage of the Glu-Ala junction (NS5-NS6), whereas substitutions at the P1 and P2′ positions altered the cleavage efficiency. The differential cleavage observed is supported by a model of the substrate-binding site of the sapovirus protease, indicating that the P4, P1, and P2′ positions in the substrate modulate the cleavage specificity and efficiency of the sapovirus chymotrypsin-like protease.",,"['Robel, Ivonne', 'Gebhardt, Julia', 'Mesters, Jeroen R.', 'Gorbalenya, Alexander', 'Coutard, Bruno', 'Canard, Bruno', 'Hilgenfeld, Rolf', 'Rohayem, Jacques']",,,,
,PMC,Structure of coronavirus hemagglutinin-esterase offers insight into corona and influenza virus evolution,http://dx.doi.org/10.1073/pnas.0800502105,PMC2449365,,,"The hemagglutinin-esterases (HEs) are a family of viral envelope glycoproteins that mediate reversible attachment to O-acetylated sialic acids by acting both as lectins and as receptor-destroying enzymes (RDEs). Related HEs occur in influenza C, toro-, and coronaviruses, apparently as a result of relatively recent lateral gene transfer events. Here, we report the crystal structure of a coronavirus (CoV) HE in complex with its receptor. We show that CoV HE arose from an influenza C-like HE fusion protein (HEF). In the process, HE was transformed from a trimer into a dimer, whereas remnants of the fusion domain were adapted to establish novel monomer–monomer contacts. Whereas the structural design of the RDE-acetylesterase domain remained unaltered, the HE receptor-binding domain underwent remodeling to such extent that the ligand is now bound in opposite orientation. This is surprising, because the architecture of the HEF site was preserved in influenza A HA over a much larger evolutionary distance, a switch in receptor specificity and extensive antigenic variation notwithstanding. Apparently, HA and HEF are under more stringent selective constraints than HE, limiting their exploration of alternative binding-site topologies. We attribute the plasticity of the CoV HE receptor-binding site to evolutionary flexibility conferred by functional redundancy between HE and its companion spike protein S. Our findings offer unique insights into the structural and functional consequences of independent protein evolution after interviral gene exchange and open potential avenues to broad-spectrum antiviral drug design.",,"['Zeng, Qinghong', 'Langereis, Martijn A.', 'van Vliet, Arno L. W.', 'Huizinga, Eric G.', 'de Groot, Raoul J.']",,,,
,PMC,Cancer Stem Cells and the Ontogeny of Lung Cancer,http://dx.doi.org/10.1200/JCO.2007.15.2702,PMC3707499,,,"Lung cancer is the leading cause of cancer death in the world today and is poised to claim approximately 1 billion lives during the 21st century. A major challenge in treating this and other cancers is the intrinsic resistance to conventional therapies demonstrated by the stem/progenitor cell that is responsible for the sustained growth, survival, and invasion of the tumor. Identifying these stem cells in lung cancer and defining the biologic processes necessary for their existence is paramount in developing new clinical approaches with the goal of preventing disease recurrence. This review summarizes our understanding of the cellular and molecular mechanisms operating within the putative cancer-initiating cell at the core of lung neoplasia.",,"['Peacock, Craig D.', 'Watkins, D. Neil']",,,,
,PMC,Treatment with proteasome inhibitor bortezomib enhances antigen-specific CD8+ T cell-mediated antitumor immunity induced by DNA vaccination,http://dx.doi.org/10.1007/s00109-008-0370-y,PMC2535907,,,"There is an urgent need to develop new innovative therapies for the control of cancer. Antigen-specific immunotherapy and the employment of proteasome inhibitors have emerged as two potentially plausible approaches for the control of cancer. In the current study, we explored the combination of the DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 (HPV-16) E7 antigen (CRT/E7) with the proteasome inhibitor; bortezomib for their ability to generate E7-specific immune responses and antitumor effects in vaccinated mice. We found that the combination of treatment with bortezomib and CRT/E7(detox) DNA generated more potent E7-specific CD8+ T cell immune responses and better therapeutic effects against TC-1 tumors in tumor bearing mice compared to monotherapy. Furthermore, we found that treatment with bortezomib led to increased apoptosis of TC-1 tumor cells and could render the TC-1 tumor cells more susceptible to lysis by E7-specific CTLs. Our data has significant implications for future clinical translation.",,"['Tseng, Chih Wen', 'Monie, Archana', 'Wu, Chao-Yi', 'Huang, Bruce', 'Wang, Mei-Cheng', 'Hung, Chien-Fu', 'Wu, T.-C.']",,,,
,PMC,Common cold,,PMC2907967,,,"INTRODUCTION: Each year, children suffer up to 5 colds and adults have 2-3 infections, leading to time off school or work, and considerable discomfort. Most symptoms resolve within a week, but coughs often persist for longer. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for common cold? We searched: Medline, Embase, The Cochrane Library and other important databases up to May 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: analgesics or anti-inflammatory drugs, antibiotics, antihistamines, decongestants (norephedrine, oxymetazoline, or pseudoephedrine), decongestants plus antihistamine, echinacea, steam inhalation, vitamin C, and zinc (intranasal gel or lozenges).",,"Arroll, Bruce",,,,
,PMC,Role of Interferon in the Replication of Human Parainfluenza Virus Type 1 Wild Type and Mutant Viruses in Human Ciliated Airway Epithelium,http://dx.doi.org/10.1128/JVI.02263-07,PMC2519580,,,"Human parainfluenza virus type 1 (HPIV1) is a significant cause of pediatric respiratory disease in the upper and lower airways. An in vitro model of human ciliated airway epithelium (HAE), a useful tool for studying respiratory virus-host interactions, was used in this study to show that HPIV1 selectively infects ciliated cells within the HAE and that progeny virus is released from the apical surface with little apparent gross cytopathology. In HAE, type I interferon (IFN) is induced following infection with an HPIV1 mutant expressing defective C proteins with an F170S amino acid substitution, rHPIV1-C(F170S), but not following infection with wild-type HPIV1. IFN induction coincided with a 100- to 1,000-fold reduction in virus titer, supporting the hypothesis that the HPIV1 C proteins are critical for the inhibition of the innate immune response. Two recently characterized live attenuated HPIV1 vaccine candidates expressing mutant C proteins were also evaluated in HAE. The vaccine candidates, rHPIV1-C(R84G/Δ170)HN(T553A)L(Y942A) and rHPIV1-C(R84G/Δ170)HN(T553A)L(Δ1710-11), which contain temperature-sensitive (ts) attenuating (att) and non-ts att mutations, were highly restricted in growth in HAE at permissive (32°C) and restrictive (37°C) temperatures. The viruses grew slightly better at 37°C than at 32°C, and rHPIV1-C(R84G/Δ170)HN(T553A)L(Y942A) was less attenuated than rHPIV1-C(R84G/Δ170)HN(T553A)L(Δ1710-11). The level of replication in HAE correlated with that previously observed for African green monkeys, suggesting that the HAE model has potential as a tool for the preclinical evaluation of HPIV1 vaccines, although how these in vitro data will correlate with vaccine virus replication in seronegative human subjects remains to be seen.",,"['Bartlett, Emmalene J.', 'Hennessey, Margaret', 'Skiadopoulos, Mario H.', 'Schmidt, Alexander C.', 'Collins, Peter L.', 'Murphy, Brian R.', 'Pickles, Raymond J.']",,,,
,PMC,Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus,http://dx.doi.org/10.1073/pnas.0711942105,PMC2430364,,,"The mortality of human infection by influenza A/H5N1 virus can exceed 80%. The high mortality and its poor response to the neuraminidase inhibitor oseltamivir have been attributed to uncontrolled virus-induced cytokine storm. We challenged BALB/c mice with 1,000 LD(50) of influenza A/Vietnam/1194/04. Survival, body weight, histopathology, inflammatory markers, viral loads, T lymphocyte counts, and neutralizing antibody response were documented in infected mice treated individually or in combination with zanamvir, celecoxib, gemfibrozil, and mesalazine. To imitate the real-life scenario, treatment was initiated at 48 h after viral challenge. There were significant improvements in survival rate (P = 0.02), survival time (P < 0.02), and inflammatory markers (P < 0.01) in the group treated with a triple combination of zanamivir, celecoxib, and mesalazine when compared with zanamivir alone. Zanamivir with or without immunomodulators reduced viral load to a similar extent. Insignificant prolongation of survival was observed when individual agents were used alone. Significantly higher levels of CD4(+) and CD8(+) T lymphocytes and less pulmonary inflammation were also found in the group receiving triple therapy. Zanamivir alone reduced viral load but not inflammation and mortality. The survival benefits of adding celecoxib and mesalazine to zanamivir could be caused by their synergistic effects in reducing cytokine dysfunction and preventing apoptosis. Combinations of a neuraminidase inhibitor with these immunomodulators should be considered in randomized controlled treatment trials of patients suffering from H5N1 infection.",,"['Zheng, Bo-Jian', 'Chan, Kwok-Wah', 'Lin, Yong-Ping', 'Zhao, Guang-Yu', 'Chan, Chris', 'Zhang, Hao-Jie', 'Chen, Hong-Lin', 'Wong, Samson S. Y.', 'Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Chan, Kwok-Hung', 'Jin, Dong-Yan', 'Yuen, Kwok-Yung']",,,,
,PMC,In This Issue,http://dx.doi.org/10.1073/iti2208105,PMC2409401,,,,,,,,,
,PMC,A recombinant subunit vaccine formulation protects against lethal Nipah virus challenge in cats,http://dx.doi.org/10.1016/j.vaccine.2008.05.016,PMC6186147,,,"Nipah virus (NiV) and Hendra virus (HeV) are closely related deadly zoonotic paramyxoviruses that have emerged and re-emerged over the last 10 years. In this study, a subunit vaccine formulation containing only recombinant, soluble, attachment glycoprotein from HeV (sG(HeV)) and CpG adjuvant was evaluated as a potential NiV vaccine in the cat model. Different amounts of sG(HeV) were employed and sG-induced immunity were examined. Vaccinated animals demonstrated varying levels of NiV–specific Ig systemically and importantly, all vaccinated cats possessed antigen-specific IgA on the mucosa. Upon oronasal challenge with NiV (50,000 TCID(50)), all vaccinated animals were protected from disease although virus was detected on day 21 post-challenge in one animal. The ability to elicit protective systemic and mucosal immunity in this animal model provides significant progress towards the development of a human subunit vaccine against henipaviruses.",,"['McEachern, Jennifer A.', 'Bingham, John', 'Crameri, Gary', 'Green, Diane J.', 'Hancock, Tim J.', 'Middleton, Deborah', 'Feng, Yan-Ru', 'Broder, Christopher C.', 'Wang, Lin-Fa', 'Bossart, Katharine N.']",,,,
,PMC,Index of Authors,,PMC2408435,,,,,,,,,
,PMC,Index of Subjects,,PMC2408434,,,,,,,,,
,PMC,Mouse-Passaged Severe Acute Respiratory Syndrome-Associated Coronavirus Leads to Lethal Pulmonary Edema and Diffuse Alveolar Damage in Adult but Not Young Mice,http://dx.doi.org/10.2353/ajpath.2008.071060,PMC2408422,,,"Advanced age is a risk factor of severe acute respiratory syndrome (SARS) in humans. To understand its pathogenesis, we developed an animal model using BALB/c mice and the mouse-passaged Frankfurt 1 isolate of SARS coronavirus (SARS-CoV). We examined the immune responses to SARS-CoV in both young and adult mice. SARS-CoV induced severe respiratory illness in all adult, but not young, mice on day 2 after inoculation with a mortality rate of 30 to 50%. Moribund adult mice showed severe pulmonary edema and diffuse alveolar damage accompanied by virus replication. Adult murine lungs, which had significantly higher interleukin (IL)-4 and lower IL-10 and IL-13 levels before infection than young murine lungs, rapidly produced high levels of proinflammatory chemokines and cytokines known to induce macrophage and neutrophil infiltration and activation (eg, tumor necrosis factor-α). On day 2 after inoculation, young murine lungs produced not only proinflammatory cytokines but also IL-2, interferon-γ, IL-10, and IL-13. Adult mice showed early and acute excessive proinflammatory responses (ie, cytokine storm) in the lungs after SARS-CoV infection, which led to severe pulmonary edema and diffuse alveolar damage. Intravenous injection with anti-tumor necrosis factor-α antibody 3 hours after infection had no effect on SARS-CoV infection. However, intraperitoneal interferon-γ injection protected adult mice from the lethal respiratory illness. The experimental model described here may be useful for elucidating the pathophysiology of SARS and for evaluating therapies to treat SARS-CoV infection.",,"['Nagata, Noriyo', 'Iwata, Naoko', 'Hasegawa, Hideki', 'Fukushi, Shuetsu', 'Harashima, Ayako', 'Sato, Yuko', 'Saijo, Masayuki', 'Taguchi, Fumihiro', 'Morikawa, Shigeru', 'Sata, Tetsutaro']",,,,
,PMC,Evaluation of an Orthogonal Pooling Strategy for Rapid High-Throughput Screening of Proteases,http://dx.doi.org/10.1089/adt.2007.110,PMC2971631,,,"Orthogonal pooling was evaluated as a strategy for the rapid screening of multiple cysteine and serine proteases against large compound libraries. To validate the method the human cysteine protease cathepsin B was screened against a library of 64,000 individual compounds and also against the same library mixed 10 compounds per well. The orthogonal pooling method used resulted in each compound being present in two wells, mixed with a different set of nine other compounds in each location. Thus hits were identified based on activity in both locations, avoiding the need for retesting of each component of active mixtures. Hits were tested in dose–response both in the dithiothreitol (DTT)-containing buffer used in the primary HTS and in buffer containing cysteine in place of DTT to rule out artifacts due to oxidative inactivation of the enzyme. Comparison of the confirmed actives from single-compound and mixture screening showed that mixture screening identified all of the actives from single-compound HTS. Based on these results the orthogonal pooling strategy has been used successfully to rapidly screen several cysteine and serine proteases.",,"['Motlekar, Nuzhat', 'Diamond, Scott L.', 'Napper, Andrew D.']",,,,
,PMC,Quiz Corner,,PMC2387257,,,,,,,,,
,PMC,Cell-based Assays to Identify Inhibitors of Viral Disease,http://dx.doi.org/10.1517/17460441.3.6.671,PMC2741327,,,"BACKGROUND: Antagonizing the production of infectious virus inside cells requires drugs that can cross the cell membrane without harming host cells. OBJECTIVE: It is therefore advantageous to establish intracellular potency of anti-viral drug candidates early in the drug-discovery pipeline. METHODS: To this end, cell-based assays are being developed and employed in high-throughput drug screening, ranging from assays that monitor replication of intact viruses to those that monitor activity of specific viral proteins. While numerous cell-based assays have been developed and investigated, rapid counter screens are also needed to define the specific viral targets of identified inhibitors and to eliminate nonspecific screening hits. RESULTS/CONCLUSIONS: Here, we describe the types of cell-based assays being used in antiviral drug screens and evaluate the equally important counter screens that are being employed to reach the full potential of cell-based high-throughput screening.",,"['Green, Neil', 'Ott, Robert D.', 'Isaacs, Richard J.', 'Fang, Hong']",,,,
,PMC,Generation of Functional Blocking Monoclonal Antibodies Against Mouse Interleukin-12 p40 Homodimer and Monomer,http://dx.doi.org/10.1089/hyb.2007.0560,PMC2673812,,,"The role of interleukin (IL)-12 (p40:p35) and IL-23 (p40:p19) is becoming clear in immune response and inflammation. However, biological functions of IL-12 p40 homodimer (p40(2)) and monomer (p40) remain poorly understood due to the lack of specific monoclonal antibodies (MAb). Earlier we have demonstrated that both p40(2) and p40 activate microglia and macrophages to induce the expression of iNOS and TNF-α. To facilitate the studies on p40(2) and p40 further, we here describe the production of neutralizing MAb against mouse p40(2) and p40 for the first time after immunization of Armenian hamsters with recombinant p40(2). Antibodies produced from clones a3-1d and d7-12c specifically recognized p40(2) but not p40, IL-12, and IL-23. These MAbs also inhibited p40(2)- but not p40-, IL-12-, and IL-23-induced production of inflammatory molecules and activation of NF-κB. On the other hand, antibodies produced from clones a3-3a and a3-7g specifically recognized p40 and inhibited p40- but not p40(2)-, IL-12-, and IL-23-induced production of inflammatory molecules and activation of NF-κB. While MAbs a3-1d and d7-12c were used to establish p40(2)-specific ELISA, we utilized MAbs a3-3a and a3-7g to develop p40-specific ELISA. Interestingly, the production of p40(2) and p40 but not IL-12 in mouse peritoneal macrophages and primary microglia was an immediate early response to bacterial lipopolysaccharides. Furthermore, double-stranded RNA, the active component of a viral infection, induced the production of p40(2) and p40 but not IL-12 in macrophages and microglia. These results indicate the presence of different regulatory mechanisms for the production of IL-12p40(2)/p40 and IL-12p70.",,"['Dasgupta, Subhajit', 'Bandopadhyay, Mausumi', 'Pahan, Kalipada']",,,,
,PMC,Lessons learned: Optimization of a murine small bowel resection model,http://dx.doi.org/10.1016/j.jpedsurg.2008.02.025,PMC2481288,,,"BACKGROUND/PURPOSE: Central to the use of murine models of disease is the ability to derive reproducible data. The purpose of this study was to determine factors contributing to variability in our murine model of small bowel resection (SBR). METHODS: Male C57Bl/6 mice were randomized to sham or 50% SBR. The effect of housing type (pathogen-free versus standard housing), nutrition (reconstituted powder versus tube feeding formulation), and correlates of intestinal morphology with gene expression changes were investigated Multiple linear regression modeling or one-way ANOVA was used for data analysis. RESULTS: Pathogen-free mice had significantly shorter ileal villi at baseline and demonstrated greater villus growth after SBR compared to mice housed in standard rooms. Food type did not affect adaptation. Gene expression changes were more consistent and significant in isolated crypt cells that demonstrated adaptive growth when compared with crypts that did not deepen after SBR. CONCLUSION: Maintenance of mice in pathogen-free conditions and restricting gene expression analysis to individual animals exhibiting morphologic adaptation enhances sensitivity and specificity of data derived from this model. These refinements will minimize experimental variability and lead to improved understanding of the complex process of intestinal adaptation.",,"['Taylor, Janice A.', 'Martin, Colin A.', 'Nair, Rajalakshmi', 'Guo, Jun', 'Erwin, Christopher R.', 'Warner, Brad W.']",,,,
,PMC,Characterization of ubiquitin and ubiquitin-like-protein isopeptidase activities,http://dx.doi.org/10.1110/ps.083450408,PMC2386736,,,"Conjugation or deconjugation of ubiquitin (Ub) or ubiquitin-like proteins (UBLs) to or from cellular proteins is a multifaceted and universal means of regulating cellular physiology, controlling the lifetime, localization, and activity of many critical proteins. Deconjugation of Ub or UBL from proteins is performed by a class of proteases called isopeptidases. Herein is described a readily quantifiable novel isopeptidase assay platform consisting of Ub or UBL fused to the reporter enzyme phospholipase A(2) (PLA(2)). Isopeptidase activity releases PLA(2), which cleaves its substrate, generating a signal that is linear with deubiquitylase (DUB) concentration and is able to discriminate DUB, deSUMOylase, deNEDDylase, and deISGylase activities. The power and sensitivity of the UBL-PLA(2) assay are demonstrated by its ability to differentiate the contrasting deISGylase and DUB activities of two coronavirus proteases: severe acute respiratory syndrome papain-like protease (SARS-CoV PLpro) and NL63 CoV papain-like protease 2 (PLP2). Furthermore, direct comparisons with the current Ub-7-amino-4-methylcoumarin (Ub-AMC) assay demonstrated that the Ub-PLA(2) assay is an effective tool for characterizing modulators of isopeptidase activity. This observation was expanded by profiling the inhibitory activity of the nonselective isopeptidase inhibitor NSC 632839 against DUBs and deSUMOylases. Taken together, these studies illustrate the utility of the reporter-based approach to measuring isopeptidase activity.",,"['Nicholson, Benjamin', 'Leach, Craig A.', 'Goldenberg, Seth J.', 'Francis, Dana M.', 'Kodrasov, Matthew P.', 'Tian, Xufan', 'Shanks, John', 'Sterner, David E.', 'Bernal, Alejandro', 'Mattern, Michael R.', 'Wilkinson, Keith D.', 'Butt, Tauseef R.']",,,,
,PMC,Evaluation of Cotton Rats as a Model for Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1089/vbz.2007.0210,PMC2978051,,,"Experimental studies were conducted to evaluate two species of cotton rats, Sigmodon hispidus and Sigmodon fulviventer, as a model for severe acute respiratory syndrome (SARS). Blood and turbinate wash samples, and lung tissue were collected from each animal at different time points after SARS coronavirus (CoV) infection for determining the growth curve of virus, if any, by the standard infectivity assay in Vero E6 cells. In addition, sections of the lung, liver, spleen, and kidney were taken and used for histology analysis. All animals were observed daily for signs of illness, and in some experiments, animals were weighed on the day when they were sacrificed. The results indicated that the cotton rat species, S. hispidus and S. fulviventer, were not a useful model for either SARS-CoV infection or disease. This observation was supported by the absence of any signs of illness, the failure to consistently demonstrate virus in the blood and tissues, and the absent of any notable histopathology. However, infected animals were capable of producing neuralizing antibodies against SARS-CoV, suggesting the serocon-version did occur. Further studies are warranted to consider other animal species in efforts to find better animal models for the evaluation of SARS-CoV vaccines and antiviral drugs. Key Words: Cotton rats—SARS—Model animal.",,"['Watts, D.M.', 'Peters, C.J.', 'Newman, P.', 'Wang, N.', 'Yoshikawa, N.', 'Tseng, C.K.', 'Wyde, P.R.']",,,,
,PMC,Heterogeneous Memory T Cells in Antiviral Immunity and Immunopathology,http://dx.doi.org/10.1089/vim.2008.0002,PMC2996251,,,"Memory T cells are generated following an initial viral infection, and have the potential for mediating robust protective immunity to viral re-challenge due to their rapid and enhanced functional responses. In recent years, it has become clear that the memory T cell response to most viruses is remarkably diverse in phenotype, function, and tissue distribution, and can undergo dynamic changes during its long-term maintenance in vivo. However, the role of this variegation and compartmentalization of memory T cells in protective immunity to viruses remains unclear. In this review, we discuss the diverse features of memory T cells that can delineate different subsets, the characteristics of memory T cells thus far identified to promote protective immune responses, and how the heterogeneous nature of memory T cells may also promote immunopathology during antiviral responses. We propose that given the profound heterogeneity of memory T cells, regulation of memory T cells during secondary responses could focus the response to participation of specific subsets, and/or inhibit memory T-cell subsets and functions that can lead to immunopathology.",,"['Verhoeven, David', 'Teijaro, John R.', 'Farber, Donna L.']",,,,
,PMC,Generation of a Protective T-Cell Response Following Coronavirus Infection of the Central Nervous System Is Not Dependent on IL-12/23 Signaling,http://dx.doi.org/10.1089/vim.2008.0014,PMC2570712,,,"The functional role of IL-12 and IL-23 in host defense and disease following viral infection of the CNS was determined. Instillation of mouse hepatitis virus (MHV, a positive-strand RNA virus) into the CNS of mice results in acute encephalitis followed by a chronic immune-mediated demyelinating disease. Antibody-mediated blocking of either IL-23 (anti-IL-23p19) or IL-12 and IL-23 (anti-IL-12/23p40) signaling did not mute T-cell trafficking into the CNS or antiviral effector responses and mice were able to control viral replication within the brain. Therapeutic administration of either anti-IL-23p19 or anti-IL-12/23p40 to mice with viral-induced demyelination did not attenuate T-cell or macrophage infiltration into the CNS nor improve clinical disease or diminish white matter damage. In contrast, treatment of mice with anti-IL-12/23p40 or anti-IL-23p19 resulted in inhibition of the autoimmune model of demyelination, experimental autoimmune encephalomyelitis (EAE). These data indicate that (1) IL-12 and IL-23 signaling are dispensable in generating a protective T-cell response following CNS infection with MHV, and (2) IL-12 and IL-23 do not contribute to demyelination in a model independent of autoimmune T-cell–mediated pathology. Therefore, therapeutic targeting of IL-12 and/or IL-23 for the treatment of autoimmune diseases may offer unique advantages by reducing disease severity without muting protective responses following viral infection.",,"['HELD, KATHERINE S.', 'GLASS, WILLIAM G.', 'ORLOVSKY, YEVGENIYA I.', 'SHAMBERGER, KIMBERLY A.', 'PETLEY, TED D.', 'BRANIGAN, PATRICK J.', 'CARTON, JILL M.', 'BECK, HEENA S.', 'CUNNINGHAM, MARK R.', 'BENSON, JACQUELINE M.', 'LANE, THOMAS E.']",,,,
,PMC,Differential role for low pH and cathepsin-mediated cleavage of the viral spike protein during entry of serotype II feline coronaviruses,http://dx.doi.org/10.1016/j.vetmic.2008.05.019,PMC2588466,,,"Feline infectious peritonitis (FIP) is a terminal disease of cats caused by systemic infection with a feline coronavirus (FCoV). FCoV biotypes that cause FIP are designated feline infectious peritonitis virus (FIPV), and are distinguished by their ability to infect macrophages and monocytes. Antigenically similar to their virulent counterparts are FCoV biotypes designated feline enteric coronavirus (FECV), which usually cause only mild enteritis and are unable to efficiently infect macrophages and monocytes. The FCoV spike protein mediates viral entry into the host cell and has previously been shown to determine the distinct tropism exhibited by certain isolates of FIPV and FECV, however the molecular mechanism underlying viral pathogenesis has yet to be determined. Here we show that the FECV strain WSU 79-1683 (FECV-1683) is highly dependent on host cell cathepsin B and cathepsin L activity for entry into the host cell, as well as on the low pH of endocytic compartments. In addition, both cathepsin B and cathepsin L are able to induce a specific cleavage event in the FECV-1683 spike protein. In contrast, host cell entry by the FIPV strains WSU 79-1146 (FIPV-1146) and FIPV-DF2 proceeds independently of cathepsin L activity and low pH, but is still highly dependent on cathepsin B activity. In the case of FIPV-1146 and FIPV-DF2, infection of primary feline monocytes was also dependent on host cell cathepsin B activity, indicating that host cell cathepsins may play a role in the distinct tropisms displayed by different feline coronavirus biotypes.",,"['Regan, Andrew D.', 'Shraybman, Renata', 'Cohen, Rebecca D.', 'Whittaker, Gary R.']",,,,
,PMC,Suppression of Astrovirus Replication by an ERK1/2 Inhibitor,http://dx.doi.org/10.1128/JVI.02193-07,PMC2493344,,,"Human astroviruses are nonenveloped, positive-sense single-strand RNA viruses associated with self-limiting diarrhea. Although they are recognized as a leading cause of disease in young children, the cellular factors involved in astrovirus replication are not well defined. The extracellular signal-regulated kinase (ERK) pathway has been shown to regulate many viral infections, but its role during astrovirus infection is unknown. In this report, we show that astrovirus activates ERK1/2 early in infection independently of replication. Inhibition of ERK activation with U0126, a specific ERK inhibitor, significantly reduced viral production. Investigations into the mechanism of ERK1/2 regulation revealed that all steps of the viral life cycle, including early and late protein expression as well as subgenomic and genomic RNA transcription, were diminished during U0126 treatment of monolayers. These data support a role for ERK1/2 in a postattachment step, although the precise mechanism remains under investigation.",,"['Moser, Lindsey A.', 'Schultz-Cherry, Stacey']",,,,
,PMC,MHC class I characterization of Indonesian cynomolgus macaques,http://dx.doi.org/10.1007/s00251-008-0292-4,PMC2612123,,,"Cynomolgus macaques (Macaca fascicularis) are quickly becoming a useful model for infectious disease and transplantation research. Even though cynomolgus macaques from different geographic regions are used for these studies, there has been limited characterization of full-length Major Histocompatibility Complex (MHC) Class I immunogenetics of distinct geographic populations. Here, we identified 48 MHC class I cDNA nucleotide sequences in eleven Indonesian cynomolgus macaques, including 41 novel Mafa-A and Mafa-B sequences. We found seven MHC class I sequences in Indonesian macaques that were identical to MHC class I sequences identified in Malaysian or Mauritian macaques. Sharing of nucleotide sequences between these geographically distinct populations is also consistent with the hypothesis that Indonesia was a source of the Mauritian macaque population. In addition, we found that the Indonesian cDNA sequence Mafa-B*7601 is identical throughout its peptide binding domain to Mamu-B*03, an allele that has been associated with control of SIV viremia in Indian rhesus macaques. Overall, a better understanding of the MHC class I alleles present in Indonesian cynomolgus macaques improves their value as a model for disease research and it better defines the biogeography of cynomolgus macaques throughout Southeast Asia.",,"['Pendley, Chad J.', 'Becker, Ericka A.', 'Karl, Julie A.', 'Blasky, Alex J.', 'Wiseman, Roger W.', 'Hughes, Austin L.', 'O’Connor, Shelby L.', 'O’Connor, David H.']",,,,
,PMC,Hematopoietic cell transplantation provides an immune-tolerant platform for myoblast transplantation in dystrophic dogs,http://dx.doi.org/10.1038/mt.2008.102,PMC2536604,,,"Duchenne Muscular Dystrophy (DMD) is the most common and severe form of muscular dystrophy in humans. The goal of myogenic stem cell transplant therapy for DMD is to increase dystrophin expression in existing muscle fibers and provide a source of stem cells for future muscle generation. Although syngeneic myogenic stem cell transplants have been successful in mice, allogeneic transplants of myogenic stem cells were ineffective in several human trials. To determine whether allogeneic muscle progenitor cells can be successfully transplanted in an immune tolerant recipient, we induced immune tolerance in two DMD affected (xmd) dogs through hematopoietic cell transplantation (HCT). Injection of freshly isolated muscle-derived cells from the HCT donor into either fully or partially chimeric xmd recipients restored dystrophin expression up to 6.72% of wild-type levels, reduced the number of centrally located nuclei, and improved muscle structure. Dystrophin expression was maintained for at least 24 weeks. Taken together, these data indicate that immune tolerance to donor myoblasts provides an important platform from which to further improve myoblast transplantation, with the goal of restoring dystrophin expression to patients with DMD.",,"['Parker, Maura H.', 'Kuhr, Christian', 'Tapscott, Stephen J.', 'Storb, Rainer']",,,,
,PMC,Human Coronavirus NL63 and 229E Seroconversion in Children,http://dx.doi.org/10.1128/JCM.00533-08,PMC2446899,,,"In 2004, the novel respiratory human coronavirus NL63 (HCoV-NL63) was identified, and subsequent research revealed that the virus has spread worldwide. HCoV-229E is a close relative of HCoV-NL63, and infection with either virus can lead to the hospitalization of young children, immunocompromised persons, and the elderly. Children infected with HCoV-NL63 often develop croup, with obstruction of the airway. In this study we investigated at which age children are confronted for the first time with an HCoV-NL63 infection and, thus, at which age they seroconvert to HCoV-NL63 positivity. We designed a recombinant HCoV-229E and a recombinant HCoV-NL63 nucleocapsid protein enzyme-linked immunosorbent assay and performed a seroepidemiology survey on longitudinal and cross-sectional serum samples. The longitudinal serum samples were collected from 13 newborns, and data for those newborns were available from multiple time points spanning a period of at least 18 months. For the cross-sectional survey we tested serum samples of 139 children, including newborns to children 16 years of age. In examinations of the longitudinal serum samples we observed that all of the children had maternal anti-NL63 and anti-229E antibodies at birth that disappeared within 3 months. Seven of the 13 children became HCoV-NL63 seropositive during follow-up, whereas only 2 became HCoV-229E seropositive. The serology data of the cross-sectional serum samples revealed that 75% and 65% of the children in the age group 2.5 to 3.5 years were HCoV-NL63 and HCoV-229E seropositive, respectively. We conclude that on average, HCoV-NL63 and HCoV-229E seroconversion occurs before children reach the age of 3.5 years.",,"['Dijkman, Ronald', 'Jebbink, Maarten F.', 'El Idrissi, Nawal Bahia', 'Pyrc, Krzysztof', 'Müller, Marcel A.', 'Kuijpers, Taco W.', 'Zaaijer, Hans L.', 'van der Hoek, Lia']",,,,
,PMC,CD13 is a novel mediator of monocytic/endothelial cell adhesion,http://dx.doi.org/10.1189/jlb.1107802,PMC2493070,,,"During inflammation, cell surface adhesion molecules guide the adhesion and migration of circulating leukocytes across the endothelial cells lining the blood vessels to access the site of injury. The transmembrane molecule CD13 is expressed on monocytes and endothelial cells and has been shown to mediate homotypic cell adhesion, which may imply a role for CD13 in inflammatory monocyte trafficking. Here, we show that ligation and clustering of CD13 by mAb or viral ligands potently induce myeloid cell/endothelial adhesion in a signal transduction-dependent manner involving monocytic cytoskeletal rearrangement and filopodia formation. Treatment with soluble recombinant (r)CD13 blocks this CD13-dependent adhesion, and CD13 molecules from monocytic and endothelial cells are present in the same immunocomplex, suggesting a direct participation of CD13 in the adhesive interaction. This concept is strengthened by the fact that activated monocytic cells adhere to immobilized recombinant CD13. Furthermore, treatment with anti-CD13 antibodies in a murine model of peritonitis results in a decrease in leukocyte infiltration into the peritoneum, suggesting a potential role for CD13 in leukocyte trafficking in vivo. Therefore, this work supports a new direction for CD13 biology, where these cell surface molecules act as true molecular interfaces that induce and participate in critical inflammatory cell interactions.",,"['Mina-Osorio, Paola', 'Winnicka, Beata', ""O'Conor, Catherine"", 'Grant, Christina L.', 'Vogel, Lotte K.', 'Rodriguez-Pinto, Daniel', 'Holmes, Kathryn V.', 'Ortega, Enrique', 'Shapiro, Linda H.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2,http://dx.doi.org/10.1128/JVI.00737-08,PMC2493326,,,"Infection of humans with the severe acute respiratory syndrome coronavirus (SARS-CoV) results in substantial morbidity and mortality, with death resulting primarily from respiratory failure. While the lungs are the major site of infection, the brain is also infected in some patients. Brain infection may result in long-term neurological sequelae, but little is known about the pathogenesis of SARS-CoV in this organ. We previously showed that the brain was a major target organ for infection in mice that are transgenic for the SARS-CoV receptor (human angiotensin-converting enzyme 2). Herein, we use these mice to show that virus enters the brain primarily via the olfactory bulb, and infection results in rapid, transneuronal spread to connected areas of the brain. This extensive neuronal infection is the main cause of death because intracranial inoculation with low doses of virus results in a uniformly lethal disease even though little infection is detected in the lungs. Death of the animal likely results from dysfunction and/or death of infected neurons, especially those located in cardiorespiratory centers in the medulla. Remarkably, the virus induces minimal cellular infiltration in the brain. Our results show that neurons are a highly susceptible target for SARS-CoV and that only the absence of the host cell receptor prevents severe murine brain disease.",,"['Netland, Jason', 'Meyerholz, David K.', 'Moore, Steven', 'Cassell, Martin', 'Perlman, Stanley']",,,,
,PMC,Single-Stranded Oligonucleotides Can Inhibit Cytokine Production Induced by Human Toll-Like Receptor 3,http://dx.doi.org/10.1128/MCB.00308-08,PMC2447120,,,"Toll-like receptor 3 (TLR3) can signal the production of a suite of cytokines and chemokines in response to double-stranded RNA (dsRNA) ligands or the dsRNA mimic poly(I-C). Using a human embryonic kidney 293T cell line to express human TLR3, we determined that poly(I-C)-induced signal could be significantly inhibited by single-stranded DNAs (ssDNAs), but not ssRNA or dsDNA. The ssDNA molecules that down-modulated TLR3 signaling did not affect TLR4 and do not require the hypomethylated CpG motif found in TLR9 ligands. The degree of modulation can be altered by the length, base sequence, and modification state of the ssDNAs. An inhibitory ssDNA was found to colocalize with TLR3 in transfected cells and in a cell line that naturally expresses TLR3. The inhibitory ssDNAs can compete efficiently with dsRNA for binding purified TLR3 ectodomains in vitro, while noninhibitory nucleic acids do not. The ssDNAs also decrease the levels of several cytokines produced by the human bronchial epithelial cell line BEAS-2B and by human peripheral blood mononuclear cells in response to poly(I-C) stimulation of native TLR3. These activities indicate that ssDNAs could be used to regulate the inflammatory response through TLR3.",,"['Ranjith-Kumar, C. T.', 'Duffy, K. E.', 'Jordan, J. L.', 'Eaton-Bassiri, A.', 'Vaughan, Robert', 'Hoose, Scott A.', 'Lamb, Roberta J.', 'Sarisky, R. T.', 'Kao, C. Cheng']",,,,
,PMC,Modulation of TNF-α-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-α production and facilitates viral entry,http://dx.doi.org/10.1073/pnas.0711241105,PMC2409424,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) is a high-risk infectious pathogen. In the proposed model of respiratory failure, SARS-CoV down-regulates its receptor, angiotensin-converting enzyme 2 (ACE2), but the mechanism involved is unknown. We found that the spike protein of SARS-CoV (SARS-S) induced TNF-α-converting enzyme (TACE)-dependent shedding of the ACE2 ectodomain. The modulation of TACE activity by SARS-S depended on the cytoplasmic domain of ACE2, because deletion mutants of ACE2 lacking the carboxyl-terminal region did not induce ACE2 shedding or TNF-α production. In contrast, the spike protein of HNL63-CoV (NL63-S), a CoV that uses ACE2 as a receptor and mainly induces the common cold, caused neither of these cellular responses. Intriguingly, viral infection, judged by real-time RT-PCR analysis of SARS-CoV mRNA expression, was significantly attenuated by deletion of the cytoplasmic tail of ACE2 or knock-down of TACE expression by siRNA. These data suggest that cellular signals triggered by the interaction of SARS-CoV with ACE2 are positively involved in viral entry but lead to tissue damage. These findings may lead to the development of anti-SARS-CoV agents.",,"['Haga, Shiori', 'Yamamoto, Norio', 'Nakai-Murakami, Chikako', 'Osawa, Yoshiaki', 'Tokunaga, Kenzo', 'Sata, Tetsutaro', 'Yamamoto, Naoki', 'Sasazuki, Takehiko', 'Ishizaka, Yukihito']",,,,
,PMC,Structure of a SARS coronavirus-derived peptide bound to the human major histocompatibility complex class I molecule HLA-B*1501,http://dx.doi.org/10.1107/S1744309108012396,PMC2496847,,,"The human leukocyte antigen (HLA) class I system comprises a highly polymorphic set of molecules that specifically bind and present peptides to cytotoxic T cells. HLA-B*1501 is a prototypical member of the HLA-B62 supertype and only two peptide–HLA-B*1501 structures have been determined. Here, the crystal structure of HLA-B*1501 in complex with a SARS coronavirus-derived nonapeptide (VQQESSFVM) has been determined at high resolution (1.87 Å). The peptide is deeply anchored in the B and F pockets, but with the Glu4 residue pointing away from the floor in the peptide-binding groove, making it available for interactions with a potential T-cell receptor.",,"['Røder, Gustav', 'Kristensen, Ole', 'Kastrup, Jette S.', 'Buus, Søren', 'Gajhede, Michael']",,,,
,PMC,Systemic delivery of HK Raf-1 siRNA Polyplexes Inhibits MDA-MB-435 Xenografts,http://dx.doi.org/10.1038/cgt.2008.29,PMC5502125,,,"Our past research has focused on identifying an effective carrier composed of histidine and lysine for delivery of nucleic acid into cells. For this purpose, we developed histidine-lysine-rich (HK) polymers with specific sequences and branching. We have found that branched HK polymers in complex with Raf-1 siRNA markedly decreased Raf-1 mRNA and induced apoptosis in cell lines in vitro. The primary focus of the present study was to determine an effective carrier to deliver siRNA systemically to tumor xenografts. After comparing HK:Raf-1 polyplexes for their in vivo efficacy, we investigated in greater detail whether one of these polymers, H3K(+H)4b, in complex with Raf-1 siRNA, inhibited the growth of MDA-MB-435 xenografts. H3K(+H)4b is a four-branched HK peptide whose predominant repeating sequence within the terminal arm is -HHHK-. After the first tail vein injection in a mouse model, there was a statistically significant reduction in tumor size between the H3K(+H)4b:Raf-1 siRNA treated and the control groups (P<0.01). By the third injection, there was nearly a 50% reduction in the Raf-1 siRNA-treated group compared to the control siRNA-treated or untreated group. Consistent with a significant effect of the HK:Raf-1 polyplex on the tumor, there were marked histological changes, increased apoptosis, and fewer vessels in the Raf-1 siRNA-treated group. Raf-1 protein within the tumor was significantly decreased after treatment with the HK:Raf-1 siRNA polyplex compared to the control treatment groups. Despite the striking effect on the tumor by the HK Raf-1 siRNA, there was little evidence of toxicity in normal tissues with this therapy. By harnessing the ability to modify the amino acid sequence and branching of HK polymers, we expect continued development of HK polymers as in vivo carriers of siRNA.",,"['Leng, Qixin', 'Scaria, Puthupparampil', 'Lu, Patrick', 'Woodle, MC', 'Mixson, A. James']",,,,
,PMC,Quantal formation of lentiviruses in cells: segregation of viral glycoproteins to lipid rafts that associate individually with HIV-1 Capsids,http://dx.doi.org/10.1016/j.chom.2008.04.004,PMC2998762,,,"The viral ribonucleoprotein complex of human immunodeficiency virus-1 (HIV-1) associates with the viral Envelope (Env) to form infectious virions. While Env and Gag are known to migrate to lipid microdomains, their stoichiometry and specificity of interaction is not known. Here, we analyze the association of different viral glycoproteins, HIV Env and Ebola GP, with HIV-1 Gag protein co-expressed in the same cell. Though these two viral spikes were both expressed, each associated independently with Gag and gave rise to two distinct virion populations, each with a spike of a single type. Confocal imaging demonstrated that HIV Env(89.6) and Ebola GP localized to distinct lipid raft microdomains within the same cell, where each associated with distinct Gag particles. Similar Env localization was observed in HIV-infected T cells, where ~14 percent of Env was associated with Gag during productive infection. Together, these data suggest that a single Gag complex associates “quantally” with an individual lipid raft microdomain to assemble functional virions during infection.",,"['Leung, Kwanyee', 'Kim, Jae-Ouk', 'Ganesh, Lakshmanan', 'Kabat, Juraj', 'Schwartz, Owen', 'Nabel, Gary J.']",,,,
,PMC,A Tetravalent Dengue Vaccine Based on a Complex Adenovirus Vector Provides Significant Protection in Rhesus Monkeys against All Four Serotypes of Dengue Virus,http://dx.doi.org/10.1128/JVI.02724-07,PMC2446963,,,"Nearly a third of the human population is at risk of infection with the four serotypes of dengue viruses, and it is estimated that more than 100 million infections occur each year. A licensed vaccine for dengue viruses has become a global health priority. A major challenge to developing a dengue vaccine is the necessity to produce fairly uniform protective immune responses to all four dengue virus serotypes. We have developed two bivalent dengue virus vaccines, using a complex adenovirus vector, by incorporating the genes expressing premembrane (prM) and envelope (E) proteins of dengue virus types 1 and 2 (dengue-1 and -2, respectively) (CAdVax-Den12) or dengue-3 and -4 (CAdVax-Den34). Rhesus macaques were vaccinated by intramuscular inoculation of a tetravalent dengue vaccine formulated by combining the two bivalent vaccine constructs. Vaccinated animals produced high-titer antibodies that neutralized all four serotypes of dengue viruses in vitro. The ability of the vaccine to induce rapid, as well as sustained, protective immune responses was examined with two separate live-virus challenges administered at 4 and 24 weeks after the final vaccination. For both of these virus challenge studies, significant protection from viremia was demonstrated for all four dengue virus serotypes in vaccinated animals. Viremia from dengue-1 and dengue-3 challenges was completely blocked, whereas viremia from dengue-2 and dengue-4 was significantly reduced, as well as delayed, compared to that of control-vaccinated animals. These results demonstrate that the tetravalent dengue vaccine formulation provides significant protection in rhesus macaques against challenge with all four dengue virus serotypes.",,"['Raviprakash, Kanakatte', 'Wang, Danher', 'Ewing, Dan', 'Holman, David H.', 'Block, Karla', 'Woraratanadharm, Jan', 'Chen, Lan', 'Hayes, Curtis', 'Dong, John Y.', 'Porter, Kevin']",,,,
,PMC,Efficient trans-Encapsidation of Hepatitis C Virus RNAs into Infectious Virus-Like Particles,http://dx.doi.org/10.1128/JVI.00118-08,PMC2446957,,,"Recently, complete replication of hepatitis C virus (HCV) in tissue culture was established using the JFH1 isolate. To analyze determinants of HCV genome packaging and virion assembly, we developed a system that supports particle production based on trans-packaging of subgenomic viral RNAs. Using JFH1 helper viruses, we show that subgenomic JFH1 replicons lacking the entire core to NS2 coding region are efficiently encapsidated into infectious virus-like particles. Similarly, chimeric helper viruses with heterologous structural proteins trans-package subgenomic JFH1 replicons. Like authentic cell culture-produced HCV (HCVcc) particles, these trans-complemented HCV particles (HCV(TCP)) penetrate target cells in a CD81 receptor-dependent fashion. Since HCV(TCP) production was limited by competition between the helper and subgenomic RNA and to avoid contamination of HCV(TCP) stocks with helper viruses, we created HCV packaging cells. These cells encapsidate various HCV replicons with high efficiency, reaching infectivity titers up to 10(6) tissue culture infectious doses 50 per milliliter. The produced particles display a buoyant density comparable to HCVcc particles and can be propagated in the packaging cell line but support only a single-round infection in naïve cells. Together, this work demonstrates that subgenomic HCV replicons are assembly competent, thus excluding cis-acting RNA elements in the core-to-NS2 genomic region essential for RNA packaging. The experimental system described here should be helpful to decipher the mechanisms of HCV assembly and to identify RNA elements and viral proteins involved in particle formation. Similar to other vector systems of plus-strand RNA viruses, HCV(TCP) may prove valuable for gene delivery or vaccination approaches.",,"['Steinmann, Eike', 'Brohm, Christiane', 'Kallis, Stephanie', 'Bartenschlager, Ralf', 'Pietschmann, Thomas']",,,,
,PMC,FILTER PERFORMANCE OF N99 AND N95 FACEPIECE RESPIRATORS AGAINST VIRUSES AND ULTRAFINE PARTICLES,http://dx.doi.org/10.1093/annhyg/men019,PMC6768072,,,"The performance of three filtering-facepiece respirators (two models of N99 and one N95) challenged with an inert aerosol (NaCl) and three virus aerosols (enterobacteriophages MS2 and T4 and Bacillus subtilis phage) – all with significant ultrafine components – was examined using a manikin-based protocol with respirators sealed on manikins. Three inhalation flowrates, 30, 85, and 150 L/min, were tested. The filter penetration and the quality factor were determined. Between-respirator and within-respirator comparisons of penetration values were performed. At the most penetrating particle size, over 3% of MS2 virions penetrated through filters of both N99 models at an inhalation flowrate of 85 L/min. Inhalation airflow had a significant effect upon particle penetration through the tested respirator filters. The filter quality factor was found suitable for making relative performance comparisons. The most-penetrating particle size for challenge aerosols was < 0.1 μm in electrical mobility diameter for all tested respirators. Mean particle penetration (by count) was significantly increased when the size fraction of <0.1 μm was included as compared to particles > 0.1 μm. The filtration performance of the N95 respirator approached that of the two models of N99 over the range of particle sizes tested (~ 0.02 – 0.5 μm). Filter penetration of the tested biological aerosols did not exceed that of inert NaCl aerosol. The results suggest that inert NaCl aerosols may generally be appropriate for modeling filter penetration of similarly-sized virions.",,"['Eninger, Robert M.', 'Honda, Takeshi', 'Adhikari, Atin', 'Heinonen-Tanski, Helvi', 'Reponen, Tiina', 'Grinshpun, Sergey A.']",,,,
,PMC,Detection of mortality clusters associated with highly pathogenic avian influenza in poultry: a theoretical analysis,http://dx.doi.org/10.1098/rsif.2008.0133,PMC2607352,,,"Rapid detection of infectious disease outbreaks is often crucial for their effective control. One example is highly pathogenic avian influenza (HPAI) such as H5N1 in commercial poultry flocks. There are no quantitative data, however, on how quickly the effects of HPAI infection in poultry flocks can be detected. Here, we study, using an individual-based mathematical model, time to detection in chicken flocks. Detection is triggered when mortality, food or water intake or egg production in layers pass recommended thresholds suggested from the experience of past HPAI outbreaks. We suggest a new threshold for caged flocks—the cage mortality detection threshold—as a more sensitive threshold than current ones. Time to detection is shown to depend nonlinearly on R(0) and is particularly sensitive for R(0)<10. It also depends logarithmically on flock size and number of birds per cage. We also examine how many false alarms occur in uninfected flocks when we vary detection thresholds owing to background mortality. The false alarm rate is shown to be sensitive to detection thresholds, dependent on flock size and background mortality and independent of the length of the production cycle. We suggest that current detection thresholds appear sufficient to rapidly detect the effects of a high R(0) HPAI strain such as H7N7 over a wide range of flock sizes. Time to detection of the effects of a low R(0) HPAI strain such as H5N1 can be significantly improved, particularly for large flocks, by lowering detection thresholds, and this can be accomplished without causing excessive false alarms in uninfected flocks. The results are discussed in terms of optimizing the design of disease surveillance programmes in general.",,"['Savill, Nicholas J', 'St. Rose, Suzanne G', 'Woolhouse, Mark E.J']",,,,
,PMC,From fish to man: understanding endogenous remyelination in CNS demyelinating diseases,http://dx.doi.org/10.1093/brain/awn076,PMC2516372,,,"In the central nervous system (CNS) of man, evolutionary pressure has preserved some capability for remyelination while axonal regeneration is very limited. In contrast, two efficient programmes of regeneration exist in the adult fish CNS, neurite regrowth and remyelination. The rapidity of CNS remyelination is critical since it not only restores fast conduction of nerve impulses but also maintains axon integrity. If myelin repair fails, axons degenerate, leading to increased disability. In the human CNS demyelinating disease Multiple Sclerosis (MS), remyelination often takes place in the midst of inflammation. Here, we discuss recent studies that address the innate repair capabilities of the axon-glia unit from fish to man. We propose that expansion of this research field will help find ways to maintain or enhance spontaneous remyelination in man.",,"['Dubois-Dalcq, Monique', 'Williams, Anna', 'Stadelmann, Christine', 'Stankoff, Bruno', 'Zalc, Bernard', 'Lubetzki, Catherine']",,,,
,PMC,Inhibition of alphavirus infection in cell culture and in mice with antisense morpholino oligomers,http://dx.doi.org/10.1016/j.virol.2008.03.032,PMC2447162,,,"The genus Alphavirus contains members that threaten human health, both as natural pathogens and as potential biological weapons. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) enter cells readily and can inhibit viral replication through sequence-specific steric blockade of viral RNA. Sindbis virus (SINV) has low pathogenicity in humans and is regularly utilized as a model alphavirus. PPMO targeting the 5′-terminal and AUG translation start site-regions of the SINV genome blocked the production of infectious SINV in tissue culture. PPMO designed against corresponding regions in Venezuelan equine encephalitis virus (VEEV) were likewise found to be effective in vitro against several strains of VEEV. Mice treated with PPMO before and after VEEV infection were completely protected from lethal outcome while mice receiving only post-infection PPMO treatment were partially protected. Levels of virus in tissue samples correlated with animal survival. Uninfected mice suffered no apparent ill-effects from PPMO treatment. Thus, PPMO appear promising as candidates for therapeutic development against alphaviruses.",,"['Paessler, Slobodan', 'Rijnbrand, Rene', 'Stein, David A.', 'Ni, Haolin', 'Yun, Nadezhda E.', 'Dziuba, Natallia', 'Borisevich, Viktoriya', 'Seregin, Alexey', 'Ma, Yinghong', 'Blouch, Robert', 'Iversen, Patrick L.', 'Zacks, Michele A.']",,,,
,PMC,Chemokines in and out of the central nervous system: much more than chemotaxis and inflammation,http://dx.doi.org/10.1189/jlb.1107763,PMC2516908,,,"Actions of chemokines and the interaction with specific receptors go beyond their original, defined role of recruiting leukocytes to inflamed tissues. Chemokine receptor expression in peripheral elements and resident cells of the central nervous system (CNS) represents a relevant communication system during neuroinflammatory conditions. The following examples are described in this review: Chemokine receptors play important homeostatic properties by regulating levels of specific ligands in blood and tissues during healthy and pathological conditions; chemokines and their receptors are clearly involved in leukocyte extravasation and recruitment to the CNS, and current studies are directed toward understanding the interaction between chemokine receptors and matrix metalloproteinases in the process of blood brain barrier breakdown. We also propose novel functions of chemokine receptors during demyelination/remyelination, and developmental processes.",,"['Cardona, Astrid E.', 'Li, Meizhang', 'Liu, Liping', 'Savarin, Carine', 'Ransohoff, Richard M.']",,,,
,PMC,IbMADS1 (Ipomoea batatas MADS-box 1 gene) is Involved in Tuberous Root Initiation in Sweet Potato (Ipomoea batatas),http://dx.doi.org/10.1093/aob/mcn067,PMC2712425,,,"BACKGROUND AND AIMS: The tuberization mechanism of sweet potato (Ipomoea batatas) has long been studied using various approaches. Morphological data have revealed that the tuberizing events result from the activation of the cambium, followed by cell proliferation. However, uncertainties still remain regarding the regulators participating in this signal-transduction pathway. An attempt was made to characterize the role of one MADS-box transcription factor, which was preferentially expressed in sweet potato roots at the early tuberization stage. METHODS: A differential expression level of IbMADS1 (Ipomoea batatas MADS-box 1) was detected temporally and spatially in sweet potato tissues. IbMADS1 responses to tuberization-related hormones were assessed. In order to identify the evolutionary significance, the expression pattern of IbMADS1 was surveyed in two tuber-deficient Ipomoea relatives, I. leucantha and I. trifida, and compared with sweet potato. In functional analyses, potato (Solanum tuberosum) was employed as a heterologous model. The resulting tuber morphogenesis was examined anatomically in order to address the physiological function of IbMADS1, which should act similarly in sweet potato. KEY RESULTS: IbMADS1 was preferentially expressed as tuberous root development proceeded. Its expression was inducible by tuberization-related hormones, such as jasmonic acid and cytokinins. In situ hybridization data showed that IbMADS1 transcripts were specifically distributed around immature meristematic cells within the stele and lateral root primordia. Inter-species examination indicated that IbMADS1 expression was relatively active in sweet potato roots, but undetectable in tuber-deficient Ipomoea species. IbMADS1-transformed potatoes exhibited tuber morphogenesis in the fibrous roots. The partial swellings along fibrous roots were mainly due to anomalous proliferation and differentiation in the xylem. CONCLUSIONS: Based on this study, it is proposed that IbMADS1 is an important integrator at the initiation of tuberization. As a result, the initiation and development of tuberous roots seems to be well regulated by a network involving a MADS-box gene in which such hormones as jasmonic acid and cytokinins may act as trigger factors.",,"['Ku, Amy Tsu', 'Huang, Yi-Shiuan', 'Wang, Yu-Shu', 'Ma, Daifu', 'Yeh, Kai-Wun']",,,,
,PMC,Comparison of the NucliSens easyMAG and Qiagen BioRobot 9604 Nucleic Acid Extraction Systems for Detection of RNA and DNA Respiratory Viruses in Nasopharyngeal Aspirate Samples,http://dx.doi.org/10.1128/JCM.00315-08,PMC2446927,,,"The NucliSens easyMAG and BioRot 9604 automated nucleic acid extraction systems were evaluated and compared with the manual QIAamp (Qiagen) extraction method for their abilities to extract nucleic acid from nasopharyngeal aspirate samples for the detection of RNA and DNA respiratory viruses. The nucleic acids recovered by all three methods gave comparable sensitivities in PCR tests, and the three methods gave comparable viral loads. There was no evidence of residual PCR inhibitors and no evidence of PCR cross-contamination.",,"['Chan, Kwok Hung', 'Yam, Wing Cheong', 'Pang, Chiu Mei', 'Chan, Kit Man', 'Lam, Siu Yan', 'Lo, Kam Fai', 'Poon, Leo L. M.', 'Peiris, J. S. Malik']",,,,
,PMC,A Live Attenuated Severe Acute Respiratory Syndrome Coronavirus Is Immunogenic and Efficacious in Golden Syrian Hamsters,http://dx.doi.org/10.1128/JVI.00304-08,PMC2493341,,,"The immunogenicity and protective efficacy of a live attenuated vaccine consisting of a recombinant severe acute respiratory syndrome (SARS) coronavirus lacking the E gene (rSARS-CoV-ΔE) were studied using hamsters. Hamsters immunized with rSARS-CoV-ΔE developed high serum-neutralizing antibody titers and were protected from replication of homologous (SARS-CoV Urbani) and heterologous (GD03) SARS-CoV in the upper and lower respiratory tract. rSARS-CoV-ΔE-immunized hamsters remained active following wild-type virus challenge, while mock-immunized hamsters displayed decreased activity. Despite being attenuated in replication in the respiratory tract, rSARS-CoV-ΔE is an immunogenic and efficacious vaccine in hamsters.",,"['Lamirande, Elaine W.', 'DeDiego, Marta L.', 'Roberts, Anjeanette', 'Jackson, Jadon P.', 'Alvarez, Enrique', 'Sheahan, Tim', 'Shieh, Wun-Ju', 'Zaki, Sherif R.', 'Baric, Ralph', 'Enjuanes, Luis', 'Subbarao, Kanta']",,,,
,PMC,An Endogenous TNF-α Antagonist Induced by Splice-switching Oligonucleotides Reduces Inflammation in Hepatitis and Arthritis Mouse Models,http://dx.doi.org/10.1038/mt.2008.85,PMC2671678,,,"Tumor necrosis factor-α (TNF-α) is a key mediator of inflammatory diseases, including rheumatoid arthritis (RA), and anti–TNF-α drugs such as etanercept are effective treatments. Splice-switching oligonucleotides (SSOs) are a new class of drugs designed to induce therapeutically favorable splice variants of targeted genes. In this work, we used locked nucleic acid (LNA)–based SSOs to modulate splicing of TNF receptor 2 (TNFR2) pre-mRNA. The SSO induced skipping of TNFR2 exon 7, which codes the transmembrane domain (TM), switching endogenous expression from the membrane-bound, functional form to a soluble, secreted form (Δ7TNFR2). This decoy receptor protein accumulated in the circulation of treated mice, antagonized TNF-α, and altered disease in two mouse models: TNF-α-induced hepatitis and collagen-induced arthritis (CIA). This is the first report of upregulation of the endogenous, circulating TNF-α antagonist by oligonucleotide-induced splicing modulation.",,"['Graziewicz, Maria A', 'Tarrant, Teresa K', 'Buckley, Brian', 'Roberts, Jennifer', 'Fulton, LeShara', 'Hansen, Henrik', 'Ørum, Henrik', 'Kole, Ryszard', 'Sazani, Peter']",,,,
,PMC,An optimized electrofusion-based protocol for generating virus-specific human monoclonal antibodies,http://dx.doi.org/10.1016/j.jim.2008.04.008,PMC2519117,,,"We sought to develop and optimize a hybridoma-based technology for generating human hybridomas that secrete virus-specific monoclonal antibodies for clinical diagnosis and therapy. We developed a novel electrofusion protocol for efficiently fusing Epstein-Barr virus (EBV)-transformed human B cells with myeloma partners. We tested seven myeloma cell lines and achieved highest efficiency when the HMMA 2.5 line was used. We optimized the electrofusion process by improving cell treatments before and after electrofusion as well as varying cell ratios, fusion medium and other experimental parameters. Our fusion efficiency increased remarkably to 0.43%, a significant improvement over the efficiency of previous PEG-based or other electrofusion methods. Using the optimized protocol, we obtained human hybridomas that secrete fully human monoclonal antibodies against two major human respiratory pathogens: respiratory syncytial virus (RSV) and an influenza H3N2 vaccine virus strain. In conclusion, we have developed an efficient and routine approach for the generation of human hybridomas secreting functional human virus-specific monoclonal antibodies.",,"['Yu, Xiaocong', 'McGraw, Patricia A.', 'House, Frances S.', 'Crowe, James E.']",,,,
,PMC,Arbovirus evolution in vivo is constrained by host alternation,http://dx.doi.org/10.1073/pnas.0712130105,PMC2383930,,,"The intrinsic plasticity of RNA viruses can facilitate host range changes that lead to epidemics. However, evolutionary processes promoting cross-species transfers are poorly defined, especially for arthropod-borne viruses (arboviruses). In theory, cross species transfers by arboviruses may be constrained by their alternating infection of disparate hosts, where optimal replication in one host involves a fitness tradeoff for the other. Accordingly, freeing arboviruses from alternate replication via specialization in a single host should accelerate adaptation. This hypothesis has been tested by using cell culture model systems with inconclusive results. Therefore, we tested it using an in vivo system with Venezuelan equine encephalitis virus (VEEV), an emerging alphavirus of the Americas. VEEV serially passaged in mosquitoes exhibited increased mosquito infectivity and vertebrate-specialized strains produced higher viremias. Conversely, alternately passaged VEEV experienced no detectable fitness gains in either host. These results suggest that arbovirus adaptation and evolution is limited by obligate host alternation and predict that arboviral emergence via host range changes may be less frequent than that of single host animal RNA viruses.",,"['Coffey, Lark L.', 'Vasilakis, Nikos', 'Brault, Aaron C.', 'Powers, Ann M.', 'Tripet, Frédéric', 'Weaver, Scott C.']",,,,
,PMC,Virus growth and antibody responses following respiratory tract infection of ferrets and mice with WT and P/V mutants of the paramyxovirus Simian Virus 5,http://dx.doi.org/10.1016/j.virol.2008.03.034,PMC2574746,,,"P/V gene substitutions convert the non-cytopathic paramyxovirus Simian Virus 5 (SV5), which is a poor inducer of host cell responses in human tissue culture cells, into a mutant (P/V-CPI–) that induces high levels of apoptosis, interferon (IFN)-beta, and proinflammatory cytokines. However, the effect of SV5-P/V gene mutations on virus growth and adaptive immune responses in animals has not been determined. Here, we used two distinct animal model systems to test the hypothesis that SV5-P/V mutants which are more potent activators of innate responses in tissue culture will also elicit higher antiviral antibody responses. In mouse cells, in vitro studies identified a panel of SV5-P/V mutants that ranged in their ability to limit IFN responses. Intranasal infection of mice with these WT and P/V mutant viruses elicited equivalent anti-SV5 IgG responses at all doses tested, and viral titers recovered from the respiratory tract were indistinguishable. In primary cultures of ferret lung fibroblasts, WT rSV5 and P/V-CPI– viruses had phenotypes similar to those established in human cell lines, including differential induction of IFN secretion, IFN signaling and apoptosis. Intranasal infection of ferrets with a low dose of WT rSV5 elicited ~500 fold higher anti-SV5 serum IgG responses compared to the P/V-CPI– mutant, and this correlated with overall higher viral titers for the WT virus in tracheal tissues. There was a dose-dependent increase in antibody response to infection of ferrets with P/V-CPI–, but not with WT rSV5. Together our data indicate that WT rSV5 and P/V mutants can elicit distinct innate and adaptive immunity phenotypes in the ferret animal model system, but not in the mouse system. We present a model for the effect of P/V gene substitutions on SV5 growth and immune responses in vivo.",,"['Capraro, Gerald A.', 'Johnson, John B.', 'Kock, Nancy D.', 'Parks, Griffith D.']",,,,
,PMC,PATHOGENICITY OF SEVERE ACUTE RESPIRATORY CORONAVIRUS DELETION MUTANTS IN hACE-2 TRANSGENIC MICE,http://dx.doi.org/10.1016/j.virol.2008.03.005,PMC2810402,,,"Recombinant severe acute respiratory virus (SARS-CoV) variants lacking the group specific genes 6, 7a, 7b, 8a, 8b and 9b (rSARS-CoV-Δ[6-9b]), the structural gene E (rSARS-CoV-ΔE), and a combination of both sets of genes (rSARS-CoV-Δ[E,6-9b]) have been generated. All these viruses were rescued in monkey (Vero E6) cells and were also infectious for human (Huh-7, Huh7.5.1 and CaCo-2) cell lines and for transgenic (Tg) mice expressing the SARS-CoV receptor human angiotensin converting enzyme-2 (hACE-2), indicating that none of these proteins is essential for the viral cycle. Furthermore, in Vero E6 cells, all the viruses showed the formation of particles with the same morphology as the wt virus, indicating that these proteins do not have a high impact in the final morphology of the virions. Nevertheless, in the absence of E protein, release of virus particles efficacy was reduced. Viruses lacking E protein grew about 100-fold lower than the wt virus in lungs of Tg infected mice but did not grow in the brains of the same animals, in contrast to the rSARS-CoV-Δ[6-9b] virus, which grew almost as well as the wt in both tissues. Viruses lacking E protein were highly attenuated in the highly sensitive hACE-2 Tg mice, in contrast to the minimal rSARS-CoV-Δ[6-9b] and wt viruses. These data indicate that E gene might be a virulence factor influencing replication level, tissue tropism and pathogenicity of SARS-CoV, suggesting that ΔE attenuated viruses are promising vaccine candidates.",,"['DeDiego, Marta L.', 'Pewe, Lecia', 'Alvarez, Enrique', 'Rejas, Maria Teresa', 'Perlman, Stanley', 'Enjuanes, Luis']",,,,
,PMC,"Pathology, Molecular Biology, and Pathogenesis of Avian Influenza A (H5N1) Infection in Humans",http://dx.doi.org/10.2353/ajpath.2008.070791,PMC2329826,,,,,"['Korteweg, Christine', 'Gu, Jiang']",,,,
,PMC,Intervening to Reduce Inequalities in Infections in Europe,http://dx.doi.org/10.2105/AJPH.2007.120329,PMC2374832,,,"The European Centre for Disease Prevention and Control was founded in response to newly emerging infections such as severe acute respiratory syndrome and avian influenza. However, Europe faces other communicable disease challenges that have proven to be remarkably resilient to public health interventions. We present examples of communicable diseases with inequitable distribution among those with poor educational attainment, low income, or other socioeconomic factors in every European country. Because these findings are incompatible with social justice and fairness, we examine strategic interventions targeting upstream causes of communicable disease transmission keeping in mind 10 indispensable public health functions essential to reach marginalized groups. These interventions have to be tailored to the socio-political context and rely on community-based decision-making and intersectorial collaboration.",,"['Semenza, Jan C.', 'Giesecke, Johan']",,,,
,PMC,Use of drotrecogin alfa (activated) in a severe acute respiratory syndrome patient with severe sepsis,,PMC2605876,,,,,"['McRitchie, Donna', 'Farooq, Warda', 'Fisher, Harold N']",,,,
,PMC,Microbiological and histopathological findings in cases of fatal bovine respiratory disease of feedlot cattle in western Canada,,PMC2359492,,,"The aim of this study was to describe the microbiologic agents and pathologic processes in fatal bovine respiratory disease (BRD) of feedlot cattle and to investigate associations between agents and pathologic processes. Ninety feedlot calves diagnosed at necropsy with BRD and 9 control calves without BRD were examined, using immunohistochemical (IHC) staining and histopathologic studies. Mannheimia haemolytica (MH) (peracute, acute, and subacute cases) and Mycoplasma bovis (MB) (subacute, bronchiolar, and chronic cases) were the most common agents identified in fatal BRD cases. Significant associations (P < 0.10) were detected between microbiologic agents and between agents and pathologic processes. When IHC staining was used, 25/26 (96%) of animals that were positive for bovine viral diarrhea virus (BVDV) were also positive for MH; 12/15 (80 %) of animals that were positive for Histophilus somni (HS) were also positive for MB; and all of the animals that were positive for HS were negative for MH and BVDV. This quantitative pathological study demonstrates that several etiologic agents and pathologic processes are involved in fatal BRD of feedlot cattle.",,"['Booker, Calvin W.', 'Abutarbush, Sameeh M.', 'Morley, Paul S.', 'Jim, G. Kee', 'Pittman, Tom J.', 'Schunicht, Oliver C.', 'Perrett, Tye', 'Wildman, Brian K.', 'Fenton, R. Kent', 'Guichon, P. Timothy', 'Janzen, Eugene D.']",,,,
,PMC,Intrahepatic endothelial and Kupffer cells involved in immunosuppressive cytokines and natural killer (NK)/NK T cell disorders in viral acute hepatitis,http://dx.doi.org/10.1111/j.1365-2249.2008.03628.x,PMC2384105,,,"During acute viral hepatitis, the intrahepatic tolerance sustained by immunosuppressive cytokines such as interleukin (IL)-4, IL-10, transforming growth factor (TGF)-β and prostaglandin E(2) (PGE(2)), produced by Kupffer cells (KC), liver sinusoidal endothelial cells (LSEC), natural killer (NK) T cells and natural regulatory T cells may be disturbed. NK cells are recruited normally in the liver and produce interferon (IFN)-γ to control viral replication. The use of mouse hepatitis virus type 3 (MHV3) attenuated variants showing selected tropisms for KC or LSEC have allowed determining their roles in the disturbances of immune tolerance during viral hepatitis. Groups of C57BL/6 mice were infected with the pathogenic L2-MHV3 (KC(+), LSEC(+)), low attenuated 51·6-MHV3 (KC(+), LSEC(−)) or high attenuated CL12-MHV3 (KC(−), LSEC(−)) variants for the first 3 days. Results showed that IL-10, TGF-β and PGE(2) production in the liver decreased in L2-MHV3-infected mice and increased in 51·6-MHV3- and CL12-MHV3-infected mice. The ratio of IFN-γ/IL-4 in liver decreased in L2-MHV3-infected mice, while it was not (or low) altered in mice infected with the attenuated MHV3 variant mice. Phenotypic analysis of intrahepatic mononuclear cells revealed that apoptotic NK and NK T cells increased in mice infected with the L2-MHV3, but were minor in 51·6-MHV3- and CL12-MHV3-infected mice. The numbers of CD4(+) forkhead box P3(+) cells increased in the livers from low pathogenic CL12-MHV3 and YAC-MHV3-infected mice. These results indicate that viral permissivity of KC and LSEC is involved in the decrease of IL-10 and PGE(2), while KC may play an additional role in the apoptosis of NK and NK T cells during acute viral hepatitis.",,"['Jacques, A', 'Bleau, C', 'Martin, J-P', 'Lamontagne, L']",,,,
,PMC,"A novel, helminth-derived immunostimulant enhances human recall responses to hepatitis C virus and tetanus toxoid and is dependent on CD56(+) cells for its action",http://dx.doi.org/10.1111/j.1365-2249.2008.03623.x,PMC2384101,,,"We have described previously an immunostimulant derived from Onchocerca volvulus, the helminth parasite that causes onchocerciasis. Recombinant O. volvulus activation-associated secreted protein-1 (rOv-ASP-1) was a potent adjuvant for antibody and cellular responses to protein, polypeptide and small peptide antigens. Our aims were to determine whether rOv-ASP-1 is immunostimulatory for human peripheral blood mononuclear cells (PBMC) and, if so, whether it could augment cellular responses against human pathogen antigens in vitro. Cytokines from rOv-ASP-1-stimulated human PBMC were measured by a fluorescence activated cell sorter-based multiplex assay. Recall responses of normal healthy donor (NHD) and chronic hepatitis C virus (c-HCV)-infected patient PBMC to tetanus toxoid (TT) or HCV core (HCVco) antigen, respectively, were measured by interferon-γ enzyme-linked immunospot assays. Interferon-γ was the predominant cytokine induced by rOv-ASP-1. 77·3% of NHD anti-TT and 88·9% of c-HCV anti-HCVco responses were enhanced by rOv-ASP-1. The immunostimulant effect was dependent upon contact between CD56(+) and CD56(−) fractions of PBMC. We have described a helminth-derived protein that can act as an immunostimulant for human recall responses in vitro to TT and, perhaps more importantly, HCV antigens in patients with chronic HCV infection. Our longer-term goal would be to boost anti-viral responses in chronic infections such as HCV.",,"['MacDonald, A J', 'Libri, N A', 'Lustigman, S', 'Barker, S J', 'Whelan, M A', 'Semper, A E', 'Rosenberg, W M']",,,,
,PMC,Special Anniversary Review: Twenty-five years of human immunodeficiency virus research: successes and challenges,http://dx.doi.org/10.1111/j.1365-2249.2008.03645.x,PMC2384092,,,"During 25 years of research since HIV-1 was first identified in Paris, there have been great advances in our understanding of the virus and of the immune system. Practical advances include the early development of diagnostic tests of infection that made blood donation safe, and since 1996, combination anti-retroviral therapy that has great reduced incidence of AIDS in HIV-infected people who have access to the drugs. HIV prevention through behavioural change has been successful, and we do not yet have any safe and efficacious microbicides or vaccines.",,"Weiss, R A",,,,
,PMC,"Mouse hepatitis virus infection of the CNS: a model for defense, disease, and repair",,PMC5025298,,,"Viral infection of the central nervous system (CNS) results in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences. One of the principal factors that directs the outcome of infection is the localized innate immune response, which is proceeded by the adaptive immune response against the invading viral pathogen. The role of the immune system is to contain and control the spread of virus within the CNS, and paradoxically, this response may also be pathological. Studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV) have provided important insights into how the immune system combats neuroinvasive viruses, and have identified molecular and cellular mechanisms contributing to chronic disease in persistently infected mice.",,"['Schaumburg, Chris S.', 'Held, Katherine S.', 'Lane, Thomas E.']",,,,
,PMC,The role of programmed-1 ribosomal frameshifting in coronavirus propagation,,PMC2435135,,,"Coronaviruses have the potential to cause significant economic, agricultural and health problems. The severe acute respiratory syndrome (SARS) associated coronavirus outbreak in late 2002, early 2003 called attention to the potential damage that coronaviruses could cause in the human population. The ensuing research has enlightened many to the molecular biology of coronaviruses. A programmed -1 ribosomal frameshift is required by coronaviruses for the production of the RNA dependent RNA polymerase which in turn is essential for viral replication. The frameshifting signal encoded in the viral genome has additional features that are not essential for frameshifting. Elucidation of the differences between coronavirus frameshift signals and signals from other viruses may help our understanding of these features. Here we summarize current knowledge and add additional insight regarding the function of the programmed -1 ribosomal frameshift signal in the coronavirus lifecycle.",,"['Plant, Ewan P.', 'Dinman, Jonathan D.']",,,,
,PMC,SNP-specific array-based allele-specific expression analysis,http://dx.doi.org/10.1101/gr.073254.107,PMC2336807,,,"We have developed an optimized array-based approach for customizable allele-specific gene expression (ASE) analysis. The central features of the approach are the ability to select SNPs at will for detection, and the absence of need to PCR amplify the target. A surprisingly long probe length (39–49 nt) was needed for allelic discrimination. Reconstitution experiments demonstrate linearity of ASE over a broad range. Using this approach, we have discovered at least two novel imprinted genes, NLRP2, which encodes a member of the inflammasome, and OSBPL1A, which encodes a presumed oxysterol-binding protein, were both preferentially expressed from the maternal allele. In contrast, ERAP2, which encodes an aminopeptidase, did not show preferential parent-of-origin expression, but rather, cis-acting nonimprinted differential allelic control. The approach is scalable to the whole genome and can be used for discovery of functional epigenetic modifications in patient samples.",,"['Bjornsson, Hans T.', 'Albert, Thomas J.', 'Ladd-Acosta, Christine M.', 'Green, Roland D.', 'Rongione, Michael A.', 'Middle, Christina M.', 'Irizarry, Rafael A.', 'Broman, Karl W.', 'Feinberg, Andrew P.']",,,,
,PMC,Construction of recombinant Lactobacillus casei efficiently surface displayed and secreted porcine parvovirus VP2 protein and comparison of the immune responses induced by oral immunization,http://dx.doi.org/10.1111/j.1365-2567.2007.02738.x,PMC2434381,,,"Lactobacillus casei ATCC 393 was selected as a bacterial carrier for the development of mucosal vaccine against porcine parvovirus (PPV) infection. The PPV major structural polypeptide VP2 was used as the model parvovirus antigen. Two inducible expression systems, namely pPG611.1 of the cell-surface expression system and pPG612.1 of the secretion expression system based on the xylose operon promoter were used to express the VP2 protein. The immunogenicity of recombinant strains producing VP2 protein in two cellular locations, cell-surface exposed and secreted, was compared to each other by immunizing mice through the intragastric administration. The two types of constructs were able to induce strong specific immune responses against VP2 via intragastric administration and maximum titres of IgA and IgG were attained on days 46 post oral immunization, while the highest antibody levels were obtained with the strain producing the VP2 protein in extracellular milieu. The induced antibodies demonstrated neutralizing effects on PPV infection.",,"['Yigang, X U', 'Yijing, L I']",,,,
,PMC,Prevention of Murine Norovirus Infection in Neonatal Mice by Fostering,,PMC2654003,,,"Murine norovirus (MNV) causes subclinical chronic infections in adult immunocompetent mice and is endemic in many mouse colonies. The susceptibility of neonatal mice to MNV infection was investigated. Intestinal homogenates from Swiss Webster (SW) mice inoculated orally with MNV-L on postpartum days (ppd) 1 to 3 were negative for MNV by RT-PCR at postinoculation days (pid) 3 and 7. In contrast, 69% of intestinal homogenates prepared on pid 3 and 7 from mice inoculated orally at ppd 5 to 8 were MNV-positive by RT-PCR. Because only mice 10 d of age or older were infected by contact with infected dams, a study was performed to determine whether fostering of neonatal mice from MNV-infected to MNV-naïve dams could be effective at preventing infection of neonatal mice. Four litters each of 1-, 2-, 4-, or 6 d-old mice from MNV-L–infected dams were transferred to naïve dams with similar-aged litters and vice versa. On ppd 21, feces from all MNV-infected dams and litters transferred to them were MNV-positive. In contrast on ppd 21, feces from all MNV-naïve dams and litters transferred to them were MNV-negative. Fostering of 2-d-old mice from 5 of 5 MNV-C–, 5 of 6 MNV-D–, and 7 of 8 MNV-G–infected dams onto MNV-naïve dams prevented MNV infection of the foster mice. In the 2 litters where MNV was detected, dams were infected within 7 d of transfer, suggesting that the neonatal mice had served as fomites. In summary, fostering was effective at preventing MNV infection in 33 of 35 litters of neonatal mice. Precautions to prevent transmission of virus on the surface of neonatal mice to foster dams could increase the efficiency of the fostering process.",,"Compton, Susan R",,,,
,PMC,Inhibition of West Nile Virus Replication by Retrovirus-Delivered Small Interfering RNA in Human Neuroblastoma Cells,http://dx.doi.org/10.1002/jmv.21164,PMC2825143,,,"West Nile virus (WNV) has been responsible for the largest outbreaks of arboviral encephalitis in U.S. history. No specific drug is currently available for the effective treatment of WNV infection. To exploit RNA interference as a potential therapeutic approach, a Moloney murine leukemia virus-based retrovirus vector was used to effectively deliver WNV-specific small interfering RNA (siRNA) into human neuroblastoma HTB-11 cells. Viral plaque assays demonstrated that transduced cells were significantly refractory to WNV replication, as compared to untransduced control cells (P< 0.05), which correlated with the reduced expression of target viral genes and respective viral proteins. Therefore, retrovirus-mediated delivery of siRNA for gene silencing can be used to study the specific functions of viral genes associated with replication and may have potential therapeutic applications.",,"['Yang, Yongbo', 'Wu, Chengxiang', 'Wu, Jianguo', 'Nerurkar, Vivek R.', 'Yanagihara, Richard', 'Lu, Yuanan']",,,,
,PMC,Emerging Pathogens: Challenges and Successes of Molecular Diagnostics,http://dx.doi.org/10.2353/jmoldx.2008.070063,PMC2329782,,,"More than 50 emerging and reemerging pathogens have been identified during the last 40 years. Until 1992 when the Institute of Medicine issued a report that defined emerging infectious diseases, medicine had been complacent about such infectious diseases despite the alarm bells of infections with human immunodeficiency virus. Molecular tools have proven useful in discovering and characterizing emerging viruses and bacteria such as Sin Nombre virus (hantaviral pulmonary syndrome), hepatitis C virus, Bartonella henselae (cat scratch disease, bacillary angiomatosis), and Anaplasma phagocytophilum (human granulocytotropic anaplasmosis). The feasibility of applying molecular diagnostics to dangerous, fastidious, and uncultivated agents for which conventional tests do not yield timely diagnoses has achieved proof of concept for many agents, but widespread use of cost-effective, validated commercial assays has yet to occur. This review presents representative emerging viral respiratory infections, hemorrhagic fevers, and hepatitides, as well as bacterial and parasitic zoonotic, gastrointestinal, and pulmonary infections. Agent characteristics, epidemiology, clinical manifestations, and diagnostic methods are tabulated for another 22 emerging viruses and five emerging bacteria. The ongoing challenge to the field of molecular diagnostics is to apply contemporary knowledge to facilitate agent diagnosis as well as to further discoveries of novel pathogens.",,"['Dong, Jianli', 'Olano, Juan P.', 'McBride, Jere W.', 'Walker, David H.']",,,,
,PMC,NKG2D contributes to efficient clearance of picornavirus from the acutely infected murine brain,http://dx.doi.org/10.1080/13550280802105002,PMC3181148,,,"Activated murine cytotoxic T cells express the NKG2D natural cytotoxicity receptor. This receptor recognizes MHC class I-like molecules expressed on the surface of infected cells and serves to augment T cell-mediated cytotoxicity. The role of NKG2D-mediated augmentation in the clearance of central nervous system viral infections has not been explored. Using the Theiler's murine encephalomyelitis virus model we found that NKG2D-positive CD8+ cytotoxic T cells enter the brain, that NKG2D ligands are expressed in the brain during acute infection, and that interruption of NKG2D ligand recognition via treatment with a function blocking antibody attenuates the efficacy of viral clearance from the central nervous system.",,"['Deb, Chandra', 'Howe, Charles L.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00636-08,PMC2346743,,,,,,,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00534-08,PMC2293070,,,,,,,,,
,PMC,Le contrôle des infections au cabinet du pédiatre,,PMC2532884,,,"RÉSUMÉ La transmission des infections au cabinet du pédiatre est de plus en plus préoccupante. Le présent document expose les voies de transmission des infections et les principes sous-jacents aux mesures actuelles pour contrôler les infections. Pour prévenir les infections, il faut bien concevoir le cabinet et adopter des politiques administratives et de triage convenables, de même que des pratiques de base pour les soins de tous les patients (p. ex., hygiène des mains, port de gants, de masques, de lunettes de protection et d’une blouse d’hôpital pour des interventions précises; nettoyage, désinfection et stérilisation convenables des surfaces et du matériel, y compris les jouets, et techniques d’asepsie en cas d’interventions effractives) et des précautions additionnelles en cas d’infections précises. Le personnel doit avoir reçu les vaccins pertinents, et les personnes infectées doivent respecter les politiques de restriction au travail.",,,,,,
,PMC,Infection control in paediatric office settings,,PMC2532878,,,"Transmission of infection in the paediatric office is of increasing concern. The present document discusses routes of transmission of infection and the principles of current infection control measures. Prevention includes appropriate office design and administrative policies, triage, routine practices for the care of all patients (eg, hand hygiene; use of gloves, masks, eye protection and gowns for specific procedures; adequate cleaning, disinfection and sterilization of surfaces and equipment including toys, and aseptic technique for invasive procedures), and additional precautions for specific infections. Personnel should be adequately immunized, and those infected should follow work-restriction policies.",,,,,,
,PMC,Structure and ion channel activity of the human respiratory syncytial virus (hRSV) small hydrophobic protein transmembrane domain,http://dx.doi.org/10.1110/ps.073366208,PMC2327286,,,"The small hydrophobic (SH) protein from the human respiratory syncytial virus (hRSV) is a glycoprotein of ∼64 amino acids with one putative α-helical transmembrane domain. Although SH protein is important for viral infectivity, its exact role during viral infection is not clear. Herein, we have studied the secondary structure, orientation, and oligomerization of the transmembrane domain of SH (SH-TM) in the presence of lipid bilayers. Only one oligomer, a pentamer, was observed in PFO-PAGE. Using polarized attenuated total reflection-Fourier transform infrared (PATR-FTIR) spectroscopy, we show that the SH-TM is α-helical. The rotational orientation of SH-TM was determined by site-specific infrared dichroism (SSID) at two consecutive isotopically labeled residues. This orientation is consistent with that of an evolutionary conserved pentameric model obtained from a global search protocol using 13 homologous sequences of RSV. Conductance studies of SH-TM indicate ion channel activity, which is cation selective, and inactive below the predicted pK(a) of histidine. Thus, our results provide experimental evidence that the transmembrane domain of SH protein forms pentameric α-helical bundles that form cation-selective ion channels in planar lipid bilayers. We provide a model for this pore, which should be useful in mutagenesis studies to elucidate its role during the virus cycle.",,"['Gan, Siok Wan', 'Ng, Lifang', 'Lin, Xin', 'Gong, Xiandi', 'Torres, Jaume']",,,,
,PMC,Transmembrane helices that form two opposite homodimeric interactions: An asparagine scan study of αM and β2 integrins,http://dx.doi.org/10.1110/ps.073234208,PMC2327277,,,"Integrins are α/β heterodimers, but recent in vitro and in vivo experiments also suggest an ability to associate through their transmembrane domains to form homomeric interactions. While the results of some in vitro experiments are consistent with an interaction mediated by a GxxxG-like motif, homo-oligomers observed after in vivo cross-linking are consistent with an almost opposite helix–helix interface. We have shown recently that both models of interaction are compatible with evolutionary conservation data, and we predicted that the α-helices in both models would have a similar rotational orientation. Herein, we have tested our prediction using in vitro asparagine scan of five consecutive residues along the GxxxG-like motif of the transmembrane domain of α and β integrins, αM and β2. We show that Asn-mediated dimerization occurs twice for every turn of the helix, consistent with two almost opposite forms of interaction as suggested previously for αIIb and β3 transmembrane domains. The orientational parameters helix tilt and rotational orientation of each of these two Asn-stabilized dimers were measured by site-specific infrared dichroism (SSID) in model lipid bilayers and were found to be consistent with our predicted computational models. Our results highlight an intrinsic tendency for integrin transmembrane α-helices to form two opposite types of homomeric interaction in addition to their heteromeric interactions and suggest that integrins may form complex and specific networks at the transmembrane domain during function.",,"['Parthasarathy, Krupakar', 'Lin, Xin', 'Tan, Suet Mien', 'Law, S.K. Alex', 'Torres, Jaume']",,,,
,PMC,Collaboration in Public Health: A New Global Imperative,,PMC2289979,,,,,"King, Lonnie J.",,,,
,PMC,Selection of peptides interfering with a ribosomal frameshift in the human immunodeficiency virus type 1,http://dx.doi.org/10.1261/rna.887008,PMC2327360,,,"The human immunodeficiency virus of type 1 (HIV-1) uses a programmed -1 ribosomal frameshift to produce the precursor of its enzymes, and changes in frameshift efficiency reduce replicative fitness of the virus. We used a fluorescent two-reporter system to screen for peptides that reduce HIV-1 frameshift in bacteria, knowing that the frameshift can be reproduced in Escherichia coli. Expression of one reporter, the green fluorescent protein (GFP), requires the HIV-1 frameshift, whereas the second reporter, the red fluorescent protein (RFP), is used to assess normal translation. A peptide library biased for RNA binding was inserted into the sequence of the protein thioredoxin and expressed in reporter-containing bacteria, which were then screened by fluorescence-activated cell sorting (FACS). We identified peptide sequences that reduce frameshift efficiency by over 50% without altering normal translation. The identified sequences are also active against different frameshift stimulatory signals, suggesting that they bind a target important for frameshifting in general, probably the ribosome. Successful transfer of active sequences to a different scaffold in a eukaryotic test system demonstrates that the anti-frameshift activity of the peptides is neither due to scaffold-dependent conformation nor effects of the scaffold protein itself on frameshifting. The method we describe identifies peptides that will provide useful tools to further study the mechanism of frameshift and may permit the development of lead compounds of therapeutic interest.",,"['Dulude, Dominic', 'Théberge-Julien, Gabriel', 'Brakier-Gingras, Léa', 'Heveker, Nikolaus']",,,,
,PMC,Development and Characterization of an Equine Infectious Anemia Virus Env-Pseudotyped Reporter Virus,http://dx.doi.org/10.1128/CVI.00088-08,PMC2446648,,,We developed a replication-defective reporter virus pseudotyped with the envelope glycoprotein of equine infectious anemia virus (EIAV). The in vitro host range and neutralization phenotype of EIAV Env-pseudotyped virus were similar to those of replication-competent virus. An EIAV Env pseudovirus will improve antigenic characterization of viral variants and evaluation of lentivirus vaccines.,,"['Tallmadge, R. L.', 'Brindley, M. A.', 'Salmans, J.', 'Mealey, R. H.', 'Maury, W.', 'Carpenter, S.']",,,,
,PMC,Serial viral infections in infants with recurrent respiratory illnesses,http://dx.doi.org/10.1183/09031936.00161907,PMC2843696,,,"To better understand the viral etiology of recurrent and prolonged illnesses, we prospectively collected nasal secretions from 285 infants at increased risk of developing asthma. Of these, 27 infants had recurrent (≥5) moderate-to-severe respiratory illnesses (MSIs), and the viral etiology of their 150 MSIs and 86 scheduled visits was analyzed by molecular diagnostics. Their demographic and clinical data were compared to those with 0-4 MSIs. Frequently ill infants had higher exposure to other children and more wheezing illnesses than less symptomatic children (p<0.0001). Viruses were detected in 136/150 (91%) MSIs, 14/21 (67%) mild illnesses and 29/65 (45%) asymptomatic visits (p=0.0001). Rhinovirus (HRV) was the most common etiologic agent (61%, 43% and 35% respectively, p=0.0020). Mixed viral infections were generally associated with more severe illnesses (27%, 0% and 5%, p=0.0001). Among the 27 frequently ill infants, only 8/150 (5.3%) MSIs were prolonged (≥2 weeks duration). Considering all samples, detection of the same virus strain ≥2 weeks apart was unusual (5.3% of all 244 positive findings). HRV infections occur early, pervasively, and repetitively in these high risk infants. Infants with prolonged or recurrent respiratory illnesses most often have a series of infections rather than persistent infection with one virus strain.",,"['Jartti, Tuomas', 'Lee, Wai-Ming', 'Pappas, Tressa', 'Evans, Michael', 'Lemanske, Robert F.', 'Gern, James E.']",,,,
,PMC,Cholesterol Effectively Blocks Entry of Flavivirus,http://dx.doi.org/10.1128/JVI.00117-08,PMC2447114,,,"Japanese encephalitis virus (JEV) and dengue virus serotype 2 (DEN-2) are enveloped flaviviruses that enter cells through receptor-mediated endocytosis and low pH-triggered membrane fusion and then replicate in intracellular membrane structures. Lipid rafts, cholesterol-enriched lipid-ordered membrane domains, are platforms for a variety of cellular functions. In this study, we found that disruption of lipid raft formation by cholesterol depletion with methyl-β-cyclodextrin or cholesterol chelation with filipin III reduces JEV and DEN-2 infection, mainly at the intracellular replication steps and, to a lesser extent, at viral entry. Using a membrane flotation assay, we found that several flaviviral nonstructural proteins are associated with detergent-resistant membrane structures, indicating that the replication complex of JEV and DEN-2 localizes to the membranes that possess the lipid raft property. Interestingly, we also found that addition of cholesterol readily blocks flaviviral infection, a result that contrasts with previous reports of other viruses, such as Sindbis virus, whose infectivity is enhanced by cholesterol. Cholesterol mainly affected the early step of the flavivirus life cycle, because the presence of cholesterol during viral adsorption greatly blocked JEV and DEN-2 infectivity. Flavirial entry, probably at fusion and RNA uncoating steps, was hindered by cholesterol. Our results thus suggest a stringent requirement for membrane components, especially with respect to the amount of cholesterol, in various steps of the flavivirus life cycle.",,"['Lee, Chyan-Jang', 'Lin, Hui-Ru', 'Liao, Ching-Len', 'Lin, Yi-Ling']",,,,
,PMC,Structural Analysis of Major Species Barriers between Humans and Palm Civets for Severe Acute Respiratory Syndrome Coronavirus Infections,http://dx.doi.org/10.1128/JVI.00442-08,PMC2446986,,,"It is believed that a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), was passed from palm civets to humans and caused the epidemic of SARS in 2002 to 2003. The major species barriers between humans and civets for SARS-CoV infections are the specific interactions between a defined receptor-binding domain (RBD) on a viral spike protein and its host receptor, angiotensin-converting enzyme 2 (ACE2). In this study a chimeric ACE2 bearing the critical N-terminal helix from civet and the remaining peptidase domain from human was constructed, and it was shown that this construct has the same receptor activity as civet ACE2. In addition, crystal structures of the chimeric ACE2 complexed with RBDs from various human and civet SARS-CoV strains were determined. These structures, combined with a previously determined structure of human ACE2 complexed with the RBD from a human SARS-CoV strain, have revealed a structural basis for understanding the major species barriers between humans and civets for SARS-CoV infections. They show that the major species barriers are determined by interactions between four ACE2 residues (residues 31, 35, 38, and 353) and two RBD residues (residues 479 and 487), that early civet SARS-CoV isolates were prevented from infecting human cells due to imbalanced salt bridges at the hydrophobic virus/receptor interface, and that SARS-CoV has evolved to gain sustained infectivity for human cells by eliminating unfavorable free charges at the interface through stepwise mutations at positions 479 and 487. These results enhance our understanding of host adaptations and cross-species infections of SARS-CoV and other emerging animal viruses.",,"Li, Fang",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Protein 6 Accelerates Murine Hepatitis Virus Infections by More than One Mechanism,http://dx.doi.org/10.1128/JVI.02406-07,PMC2446958,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) encodes numerous accessory proteins whose importance in the natural infection process is currently unclear. One of these accessory proteins is set apart by its function in the context of a related murine hepatitis virus (MHV) infection. SARS-CoV protein 6 increases MHV neurovirulence and accelerates MHV infection kinetics in tissue culture. Protein 6 also blocks nuclear import of macromolecules from the cytoplasm, a process known to involve its C-terminal residues interacting with cellular importins. In this study, protein 6 was expressed from plasmid DNAs and accumulated in cells prior to infection by wild-type MHV. Output of MHV progeny was significantly increased by preexisting protein 6. Protein 6 with C-terminal deletion mutations no longer interfered with nuclear import processes but still retained much of the capacity to augment MHV infections. However, some virus growth-enhancing activity could be ascribed to the C-terminal end of protein 6. To determine whether this augmentation provided by the C terminus was derived from interference with nuclear import, we evaluated the virus-modulating effects of small interfering RNAs (siRNAs) directed against importin-β mRNAs, which down-regulated classical nuclear import pathways. The siRNAs did indeed prime cells for enhanced MHV infection. Our findings indicated that protein 6-mediated nuclear import blocks augmented MHV infections but is clearly not the only way that this accessory protein operates to create a milieu conducive to robust virus growth. Thus, the SARS-CoV protein 6 accelerates MHV infections by more than one mechanism.",,"['Hussain, Snawar', 'Perlman, Stanley', 'Gallagher, Thomas M.']",,,,
,PMC,The Nucleocapsid Protein of Severe Acute Respiratory Syndrome Coronavirus Inhibits Cell Cytokinesis and Proliferation by Interacting with Translation Elongation Factor 1α,http://dx.doi.org/10.1128/JVI.00133-08,PMC2446950,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS, an emerging disease characterized by atypical pneumonia. Using a yeast two-hybrid screen with the nucleocapsid (N) protein of SARS-CoV as a bait, the C terminus (amino acids 251 to 422) of the N protein was found to interact with human elongation factor 1-alpha (EF1α), an essential component of the translational machinery with an important role in cytokinesis, promoting the bundling of filamentous actin (F-actin). In vitro and in vivo interaction was then confirmed by immuno-coprecipitation, far-Western blotting, and surface plasmon resonance. It was demonstrated that the N protein of SARS-CoV induces aggregation of EF1α, inhibiting protein translation and cytokinesis by blocking F-actin bundling. Proliferation of human peripheral blood lymphocytes and other human cell lines was significantly inhibited by the infection of recombinant retrovirus expressing SARS-CoV N protein.",,"['Zhou, Bing', 'Liu, Junli', 'Wang, Qiuna', 'Liu, Xuan', 'Li, Xiaorong', 'Li, Ping', 'Ma, Qingjun', 'Cao, Cheng']",,,,
,PMC,INHIBITION OF RESPIRATORY SYNCYTIAL VIRUS INFECTION IN CELL CULTURES AND IN MICE WITH MORPHOLINO OLIGOMERS,http://dx.doi.org/10.1038/mt.2008.81,PMC2782410,,,"Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in infants, young children, and high-risk adults. Currently, there is no vaccine for the prevention of RSV infection, and available therapeutics are of limited utility. Peptide conjugated phosphorodiamidate morpholino oligomers (PPMO) are a class of antisense agents that can enter cells readily and interfere with viral protein expression through steric blocking of complementary RNA. Two antisense PPMO, designed to target sequence that includes the 5′ terminal- and translation start site-regions of RSV L mRNA, were tested for anti-RSV activity in cultures of two human airway cell lines. Both PPMO showed minimal cytotoxicity, and one of them (AUG-2), reduced viral titers by more than 2.0 log(10). Intranasal treatment of BALB/c mice with AUG-2 PPMO prior to RSV inoculation produced a reduction in viral titer of 1.2 log(10) in lung tissue at day 5 post-infection, and attenuated pulmonary inflammation at day 7 post-infection. These data show that the AUG-2 PPMO possessed potent anti-RSV activity and is worthy of further investigation as a candidate for therapeutic development.",,"['Lai, Shen-Hao', 'Stein, David A.', 'Guerrero-Plata, Antonieta', 'Liao, Sui-Ling', 'Ivanciuc, Teodora', 'Hong, Chao', 'Iversen, Patrick L.', 'Casola, Antonella', 'Garofalo, Roberto P.']",,,,
,PMC,Titration of Human Coronaviruses Using an Immunoperoxidase Assay,http://dx.doi.org/10.3791/751,PMC2582848,,,"Calculation of infectious viral titers represents a basic and essential experimental approach for virologists. Classical plaque assays cannot be used for viruses that do not cause significant cytopathic effects, which is the case for strains 229E and OC43 of human coronavirus (HCoV). An alternative indirect immunoperoxidase assay (IPA) is herein described for the detection and titration of these viruses. Susceptible cells are inoculated with serial logarithmic dilutions of samples in a 96-well plate. After viral growth, viral detection by IPA yields the infectious virus titer, expressed as ""Tissue Culture Infectious Dose"" (TCID50). This represents the dilution of a virus-containing sample at which half of a series of laboratory wells contain replicating virus. This technique is a reliable method for the titration of HCoV in biological samples (cells, tissues or fluids).",,"['Lambert, Francine', 'Jacomy, Helene', 'Marceau, Gabriel', 'J. Talbot, Pierre']",,,,
,PMC,A combinatorial library of lipid-like materials for delivery of RNAi therapeutics,http://dx.doi.org/10.1038/nbt1402,PMC3014085,,,"The safe and effective delivery of RNA interference (RNAi) therapeutics remains an important challenge for clinical development. The diversity of current delivery materials remains limited, in part because of their slow, multi-step syntheses. Here we describe a new class of lipid-like delivery molecules, termed lipidoids, as delivery agents for RNAi therapeutics. Chemical methods were developed to allow the rapid synthesis of a large library of over 1,200 structurally diverse lipidoids. From this library, we identified lipidoids that facilitate high levels of specific silencing of endogenous gene transcripts when formulated with either double-stranded small interfering RNA (siRNA) or single-stranded antisense 2′-O-methyl (2′-O Me) oligoribonucleotides targeting microRNA (miRNA). The safety and efficacy of lipidoids were evaluated in three animal models: mice, rats and nonhuman primates. The studies reported here suggest that these materials may have broad utility for both local and systemic delivery of RNA therapeutics.",,"['Akinc, Akin', 'Zumbuehl, Andreas', 'Goldberg, Michael', 'Leshchiner, Elizaveta S', 'Busini, Valentina', 'Hossain, Naushad', 'Bacallado, Sergio A', 'Nguyen, David N', 'Fuller, Jason', 'Alvarez, Rene', 'Borodovsky, Anna', 'Borland, Todd', 'Constien, Rainer', 'de Fougerolles, Antonin', 'Dorkin, J Robert', 'Jayaprakash, K Narayanannair', 'Jayaraman, Muthusamy', 'John, Matthias', 'Koteliansky, Victor', 'Manoharan, Muthiah', 'Nechev, Lubomir', 'Qin, June', 'Racie, Timothy', 'Raitcheva, Denitza', 'Rajeev, Kallanthottathil G', 'Sah, Dinah W Y', 'Soutschek, Jürgen', 'Toudjarska, Ivanka', 'Vornlocher, Hans-Peter', 'Zimmermann, Tracy S', 'Langer, Robert', 'Anderson, Daniel G']",,,,
,PMC,Angiotensin converting enzyme-2 is protective but downregulated in human and experimental lung fibrosis,http://dx.doi.org/10.1152/ajplung.00009.2008,PMC2494775,,,"Earlier work from this laboratory showed that local generation of angiotensin (ANG) II is required for the pathogenesis of experimental pulmonary fibrosis and that ANG peptides are expressed robustly in the lungs of patients with idiopathic pulmonary fibrosis (IPF). Angiotensin converting enzyme-2 (ACE-2) degrades the octapeptide ANG II to form the heptapeptide ANG1-7 and thereby limits ANG II accumulation. On this basis, we hypothesized that ACE-2 would be protective against experimental lung fibrogenesis and might be downregulated in human and experimental lung fibrosis. In lung biopsy specimens from patients with IPF, ACE-2 mRNA and enzyme activity were decreased by 92% (P < 0.01) and 74% (P < 0.05), respectively. ACE-2 mRNA and activity were also decreased similarly in the lungs of bleomycin-treated rats and C57-BL6 mice. In mice exposed to low doses of bleomycin, lung collagen accumulation was enhanced by intratracheal administration of either ACE-2-specific small interfering RNAs (siRNAs) or the peptide DX(600), a competitive inhibitor of ACE-2 (P < 0.05). Administration of either ACE-2 siRNA or DX(600) significantly increased the ANG II content of mouse lung tissue above the level induced by bleomycin alone. Coadministration of the ANG II receptor antagonist saralasin blocked the DX(600)-induced increase in lung collagen. Moreover, purified recombinant human ACE-2, delivered to mice systemically by osmotic minipump, attenuated bleomycin-induced lung collagen accumulation. Together, these data show that ACE-2 mRNA and activity are severely downregulated in both human and experimental lung fibrosis and suggest that ACE-2 protects against lung fibrogenesis by limiting the local accumulation of the profibrotic peptide ANG II.",,"['Li, Xiaopeng', 'Molina-Molina, Maria', 'Abdul-Hafez, Amal', 'Uhal, Victor', 'Xaubet, Antonio', 'Uhal, Bruce D.']",,,,
,PMC,New angiotensins,http://dx.doi.org/10.1007/s00109-008-0340-4,PMC2713173,,,"Accumulation of a large body of evidence during the past two decades testifies to the complexity of the renin–angiotensin system (RAS). The incorporation of novel enzymatic pathways, resulting peptides, and their corresponding receptors into the biochemical cascade of the RAS provides a better understanding of its role in the regulation of cardiovascular and renal function. Hence, in recent years, it became apparent that the balance between the two opposing effector peptides, angiotensin II and angiotensin-(1–7), may have a pivotal role in determining different cardiovascular pathophysiologies. Furthermore, our recent studies provide evidence for the functional relevance of a newly discovered rat peptide, containing two additional amino acid residues compared to angiotensin I, first defined as proangiotensin-12 [angiotensin-(1–12)]. This review focuses on angiotensin-(1–7) and its important contribution to cardiovascular function and growth, while introducing angiotensin-(1–12) as a potential novel angiotensin precursor.",,"['Varagic, Jasmina', 'Trask, Aaron J.', 'Jessup, Jewell A.', 'Chappell, Mark C.', 'Ferrario, Carlos M.']",,,,
,PMC,Health geography: supporting public health policy and planning,http://dx.doi.org/10.1503/cmaj.071783,PMC2292766,,,,,"Dummer, Trevor J.B.",,,,
,PMC,Immunosuppression in islet transplantation,http://dx.doi.org/10.1172/JCI35639,PMC2323197,,,"Islet transplantation can temporarily cure type 1 diabetes mellitus (T1DM) but requires simultaneous immunosuppression to avoid allograft rejection. In this issue of the JCI, Monti et al. report that immune conditioning via use of the Edmonton protocol — a treatment approach in which T1DM patients infused with pancreatic islets from multiple cadaveric donors simultaneously receive immunosuppressive drugs — results in lymphopenia that is associated with elevated serum levels of the homeostatic cytokines IL-7 and IL-15, which causes in vivo expansion of the autoreactive CD8(+) T cell population (see the related article beginning on page 1806). Reemergence of autoreactivity is likely the main culprit underlying long-term islet graft failure, and new strategies will need to be tested to circumvent this homeostatic expansion and recurrent autoreactivity.",,"['Van Belle, Tom', 'von Herrath, Matthias']",,,,
,PMC,Molecular Targets for Diagnostics and Therapeutics of Severe Acute Respiratory Syndrome (SARS-CoV),,PMC2678938,,,"PURPOSE: The large number of deaths in a short period of time due to the spread of severe acute respiratory syndrome (SARS) infection led to the unparalleled collaborative efforts world wide to determine and characterize the new coronavirus (SARS-CoV). The full genome sequence was determined within weeks of the first outbreak by the Canadian group with international collaboration. As per the World Health Organization (WHO), the continual lack of a rapid laboratory test to aid the early diagnosis of suspected cases of SARS makes this area a priority for future research. To prevent deaths in the future, early diagnosis and therapy of this infectious disease is of paramount importance. METHODS: This review describes the specific molecular targets for diagnostics and therapeutics of viral infection. RESULTS: The three major diagnostic methods available for SARS includes viral RNA detection by reverse transcription polymerase chain reaction (RT-PCR), virus induced antibodies by immunofluorescence assay (IFA) or by enzyme linked immunosorbant assay (ELISA) of nucleocapsid protein (NP). The spike glycoprotein of SARS-CoV is the major inducer of neutralizing antibodies. The receptor binding domain (RBD) in the S1 region of the spike glycoprotein contains multiple conformational epitopes that induces highly potent neutralizing antibodies. The genetically engineered attenuated form of the virus or viral vector vaccine encoding for the SARS-CoV spike glycoprotein has been shown to elicit protective immunity in vaccinated animals. CONCLUSION: NP is the preferred target for routine detection of SARS-CoV infection by ELISA which is an economical method compared to other methods. The RBD of the spike glycoprotein is both a functional domain for cell receptor binding and also a major neutralizing determinant of SARS-CoV. The progress in evaluating a therapeutic or vaccine would depend on the availability of clinically relevant animal model.",,"['Bhatnagar, Pravin K.', 'Das, Dipankar', 'Suresh, Mavanur R.']",,,,
,PMC,Importance of SARS-CoV Spike Protein Trp-rich Region in Viral Infectivity,http://dx.doi.org/10.1016/j.bbrc.2008.04.044,PMC2519895,,,"SARS-CoV entry is mediated by spike glycoprotein. During the viral and host cellular membrane fusion, HR1 and HR2 form 6-helix bundle, positioning the fusion peptide closely to the C-terminal region of ectodomain to drive apposition and subsequent membrane fusion. Connecting to the HR2 region is a Trp-rich region which is absolutely conserved in members of coronaviruses. To investigate the importance of Trp-rich region in SARS-CoV entry, we produced different mutated S proteins using Alanine scan strategy. SARS-CoV pseudotyped with mutated S protein was used to measure viral infectivity. To restore the aromaticity of Ala-mutants, we performed rescue experiments using phenylalanine substitutions. Our results show that individually-substituted Ala-mutants substantially decrease infectivity by >90%, global Ala-mutants totally abrogated infectivity. In contrast, Phe-substituted mutants are able to restore 10–25% infectivity comparing to the wild type. The results suggest that the Trp-rich region of S protein is essential for SARS-CoV infectivity.",,"['Lu, Yanning', 'Neo, Tuan Ling', 'Liu, Ding Xiang', 'Tam, James P.']",,,,
,PMC,Coronavirus Nonstructural Protein 16 Is a Cap-0 Binding Enzyme Possessing (Nucleoside-2′O)-Methyltransferase Activity,http://dx.doi.org/10.1128/JVI.00407-08,PMC2519555,,,"The coronavirus family of positive-strand RNA viruses includes important pathogens of livestock, companion animals, and humans, including the severe acute respiratory syndrome coronavirus that was responsible for a worldwide outbreak in 2003. The unusually complex coronavirus replicase/transcriptase is comprised of 15 or 16 virus-specific subunits that are autoproteolytically derived from two large polyproteins. In line with bioinformatics predictions, we now show that feline coronavirus (FCoV) nonstructural protein 16 (nsp16) possesses an S-adenosyl-l-methionine (AdoMet)-dependent RNA (nucleoside-2′O)-methyltransferase (2′O-MTase) activity that is capable of cap-1 formation. Purified recombinant FCoV nsp16 selectively binds to short capped RNAs. Remarkably, an N7-methyl guanosine cap ((7Me)GpppAC(3-6)) is a prerequisite for binding. High-performance liquid chromatography analysis demonstrated that nsp16 mediates methyl transfer from AdoMet to the 2′O position of the first transcribed nucleotide, thus converting (7Me)GpppAC(3-6) into (7Me)GpppA(2′)(O)(Me)C(3-6). The characterization of 11 nsp16 mutants supported the previous identification of residues K45, D129, K169, and E202 as the putative K-D-K-E catalytic tetrad of the enzyme. Furthermore, residues Y29 and F173 of FCoV nsp16, which may be the functional counterparts of aromatic residues involved in substrate recognition by the vaccinia virus MTase VP39, were found to be essential for both substrate binding and 2′O-MTase activity. Finally, the weak inhibition profile of different AdoMet analogues indicates that nsp16 has evolved an atypical AdoMet binding site. Our results suggest that coronavirus mRNA carries a cap-1, onto which 2′O methylation follows an order of events in which 2′O-methyl transfer must be preceded by guanine N7 methylation, with the latter step being performed by a yet-unknown N7-specific MTase.",,"['Decroly, Etienne', 'Imbert, Isabelle', 'Coutard, Bruno', 'Bouvet, Mickaël', 'Selisko, Barbara', 'Alvarez, Karine', 'Gorbalenya, Alexander E.', 'Snijder, Eric J.', 'Canard, Bruno']",,,,
,PMC,Priming of CD8(+) T Cells during Central Nervous System Infection with a Murine Coronavirus Is Strain Dependent,http://dx.doi.org/10.1128/JVI.00106-08,PMC2447063,,,"Virus-specific CD8(+) T cells are critical for protection against neurotropic coronaviruses; however, central nervous system (CNS) infection with the recombinant JHM (RJHM) strain of mouse hepatitis virus (MHV) elicits a weak CD8(+) T-cell response in the brain and causes lethal encephalomyelitis. An adoptive transfer model was used to elucidate the kinetics of CD8(+) T-cell priming during CNS infection with RJHM as well as with two MHV strains that induce a robust CD8(+) T-cell response (RA59 and SJHM/RA59, a recombinant A59 virus expressing the JHM spike). While RA59 and SJHM/RA59 infections resulted in CD8(+) T-cell priming within the first 2 days postinfection, RJHM infection did not lead to proliferation of naïve CD8(+) T cells. While all three viruses replicated efficiently in the brain, only RA59 and SJHM/RA59 replicated to appreciable levels in the cervical lymph nodes (CLN), the site of T-cell priming during acute CNS infection. RJHM was unable to suppress the CD8(+) T-cell response elicited by RA59 in mice simultaneously infected with both strains, suggesting that RJHM does not cause generalized immunosuppression. RJHM was also unable to elicit a secondary CD8(+) T-cell response in the brain following peripheral immunization against a viral epitope. Notably, the weak CD8(+) T-cell response elicited by RJHM was unique to CNS infection, since peripheral inoculation induced a robust CD8(+) T-cell response in the spleen. These findings suggest that the failure of RJHM to prime a robust CD8(+) T-cell response during CNS infection is likely due to its failure to replicate in the CLN.",,"['MacNamara, Katherine C.', 'Bender, Susan J.', 'Chua, Ming Ming', 'Watson, Richard', 'Weiss, Susan R.']",,,,
,PMC,Mouse Models for the Study of HCV Infection and Virus-host Interactions,http://dx.doi.org/10.1016/j.jhep.2008.03.012,PMC2529177,,,"Hepatitis C virus (HCV) is a major cause of chronic liver disease including steatosis, cirrhosis and hepatocellular carcinoma. The development of transgenic mice expressing HCV proteins and the successful repopulation of SCID/Alb-uPA mice with human hepatocytes provides an important tool for unraveling virus-host interactions in vivo. Several of these mouse models exhibit aspects of HCV-related liver disease. Thus, these in vivo models play an important role to further understand the pathogenesis of HCV infection and to evaluate the preclinical safety and efficacy of new antiviral compounds against HCV. This review summarizes the most important mouse models currently used to study HCV pathogenesis and infection. Finally, the perspective for these models for future HCV research as well as the design of novel small animal models is discussed.",,"['Barth, Heidi', 'Robinet, Eric', 'Liang, T. Jake', 'Baumert, Thomas F.']",,,,
,PMC,Detection of apoptosis induced by new type gosling viral enteritis virus in vitro through fluorescein annexin V-FITC/PI double labeling,http://dx.doi.org/10.3748/wjg.14.2174,PMC2703841,,,"AIM: To achieve a better understanding of the pathogenesis of new type gosling viral enteritis virus (NGVEV) and the relationship between NGVEV and host cells. METHODS: The apoptosis of duck embryo fibroblasts (DEF) induced by NGVEV was investigated by fluorescence-activated cell sorter (FACS) and fluorescence microscope after the cells were stained with Annexin V-FITC and propidium iodide (PI). RESULTS: By staining cells with a combination of fluorescein annexin V-FITC and PI, it is possible to distinguish and quantitatively analyze non-apoptotic cells (Annexin V-FITC negative/PI negative), early apoptotic cells (Annexin V-FITC positive/PI negative), late apoptotic/necrotic cells (Annexin V-FITC positive/PI positive) and dead cells (Annexin V-FITC negative/PI positive) through flow cytometry and fluorescence microscope. The percentage of apoptotic cells increased with the incubation time and reached a maximum at 120 h after infection, while the percentage of non-apoptotic cells decreased. CONCLUSION: NGVEV can induce the infected DEF cells to undergo apoptosis and the apoptosis occurs prior to necrosis.",,"['Chen, Shun', 'Cheng, An-Chun', 'Wang, Ming-Shu', 'Peng, Xi']",,,,
,PMC,Interferon alfacon 1 inhibits SARS-CoV infection In human bronchial epithelial Calu-3 cells,http://dx.doi.org/10.1016/j.bbrc.2008.04.006,PMC2441846,,,"The primary targets for SARS-CoV infection are the epithelial cells in the respiratory and intestinal tract. The angiotensin-converting enzyme 2 (ACE-2) has been identified as a functional receptor for SARS-CoV. ACE-2 has been shown to be expressed at the apical domain of polarized Calu-3 cells. In this report, interferon alfacon 1 was examined for inhibitory activities against SARS-CoV on human lung carcinoma epithelial Calu-3 cell line and the other three African green monkey kidney epithelial cell lines. Interferon alfacon 1 demonstrated significant antiviral activity in neutral red uptake assay and virus yield reduction assay. The data might provide an important insight into the mechanism of pathogenesis of SARS-CoV allowing further development of antiviral therapies for treating SARS infections.",,"['Kumaki, Yohichi', 'Day, Craig W.', 'Wandersee, Miles K.', 'Schow, Bradley P.', 'Madsen, Justin S.', 'Grant, Dixon', 'Blatt, Lawrence M.', 'Barnard, Dale L.']",,,,
,PMC,Cluster Intradermal DNA Vaccination Rapidly Induces E7-specific CD8(+) T Cell Immune Responses Leading to Therapeutic Antitumor Effects,http://dx.doi.org/10.1038/gt.2008.53,PMC2888272,,,"Intradermal administration of DNA vaccines via a gene gun represents a feasible strategy to deliver DNA directly into the professional antigen-presenting cells (APCs) in the skin. This helps to facilitate the enhancement of DNA vaccine potency via strategies that modify the properties of APCs. We have previously demonstrated that DNA vaccines encoding human papillomavirus type 16 (HPV-16) E7 antigen linked to calreticulin (CRT) are capable of enhancing the E7-specific CD8(+) T cell immune responses and antitumor effects against E7-expressing tumors. It has also been shown that cluster (short-interval) DNA vaccination regimen generates potent immune responses in a minimal timeframe. Thus, in the current study we hypothesize that the cluster intradermal CRT/E7 DNA vaccination will generate significant antigen-specific CD8(+) T cell infiltrates in E7-expressing tumors in tumor-bearing mice, leading to an increase in apoptotic tumor cell death. We found that cluster intradermal CRT/E7 DNA vaccination is capable of rapidly generating a significant number of E7-specific CD8(+) T cells, resulting in significant therapeutic antitumor effects in vaccinated mice. We also observed that cluster intradermal CRT/E7 DNA vaccination in the presence of tumor generates significantly higher E7-specific CD8(+) T cell immune responses in the systemic circulation as well as in the tumors. In addition, this vaccination regimen also led to significantly lower levels of CD4(+)Foxp3(+) T regulatory cells and myeloid suppressor cells compared to vaccination with CRT DNA in peripheral blood and in tumor infiltrating lymphocytes, resulting in an increase in apoptotic tumor cell death. Thus, our study has significant potential for future clinical translation.",,"['Peng, Shiwen', 'Trimble, Cornelia', 'Alvarez, Ronald D.', 'Huh, Warner K.', 'Lin, Zhenhua', 'Monie, Archana', 'Hung, Chien-Fu', 'Wu, T.-C.']",,,,
,PMC,"KINETIC CHARACTERIZATION AND MOLECULAR DOCKING OF A NOVEL, POTENT, AND SELECTIVE SLOW-BINDING INHIBITOR OF HUMAN CATHEPSIN L",http://dx.doi.org/10.1124/mol.108.046219,PMC2575030,,,"A novel small molecule thiocarbazate (PubChem SID 26681509), a potent inhibitor of human cathepsin L (EC 3.4.22.15) with an IC(50) of 56 nM, was developed following a 57,821 compound screen of the NIH Molecular Libraries Small Molecule Repository. After a 4 hr preincubation with cathepsin L, this compound became even more potent, demonstrating an IC(50) of 1.0 nM. The thiocarbazate was determined to be a slow-binding and slowly reversible competitive inhibitor. Through a transient kinetic analysis for single-step reversibility, inhibition rate constants were k(on) = 24,000 M(-1)s(-1) and k(off) = 2.2 × 10(-5) s(-1) (K(i) = 0.89 nM). Molecular docking studies were undertaken using the experimentally-derived X-ray crystal structure of papain/CLIK-148 (1cvz.pdb). These studies revealed critical hydrogen bonding patterns of the thiocarbazate with key active site residues in papain. The thiocarbazate displayed 7- to 151-fold greater selectivity toward cathepsin L than papain and cathepsins B, K, V, and S with no activity against cathepsin G. The inhibitor demonstrated a lack of toxicity in human aortic endothelial cells and zebrafish. Additionally, the thiocarbazate inhibited in vitro propagation of malaria parasite Plasmodium falciparum with an IC(50) of 15.4 μM and inhibited Leishmania major with an IC(50) of 12.5 μM.",,"['Shah, Parag P.', 'Myers, Michael C.', 'Beavers, Mary Pat', 'Purvis, Jeremy E.', 'Jing, Huiyan', 'Grieser, Heather J.', 'Sharlow, Elizabeth R.', 'Napper, Andrew D.', 'Huryn, Donna M.', 'Cooperman, Barry S.', 'Smith, Amos B.', 'Diamond, Scott L.']",,,,
,PMC,Development and Evaluation of a Novel Multiplex PCR Technology for Molecular Differential Detection of Bacterial Respiratory Disease Pathogens,http://dx.doi.org/10.1128/JCM.01858-07,PMC2446872,,,The ResPlex I assay (Qiagen) was designed to amplify and detect DNA of six bacterial respiratory pathogens. This assay was compared with real-time PCR assays based upon the same target sequences for the ability detect the target bacteria by use of both stock strains and specimens from respiratory disease patients. The ResPlex I assay is somewhat less sensitive than real-time PCR assays but offers the advantage of multiple assays in a single reaction.,,"['Benson, Robert', 'Tondella, Maria L.', 'Bhatnagar, Julu', 'Carvalho, Maria da Glória S.', 'Sampson, Jacquelyn S.', 'Talkington, Deborah F.', 'Whitney, Anne M.', 'Mothershed, Elizabeth', 'McGee, Lesley', 'Carlone, George', 'McClee, Vondguraus', 'Guarner, Jeannette', 'Zaki, Sherif', 'Dejsiri, Surang', 'Cronin, K.', 'Han, Jian', 'Fields, Barry S.']",,,,
,PMC,Mutagenesis of the Active-Site Cysteine in the Ubiquitin-Specific Protease Contained in Large Tegument Protein pUL36 of Pseudorabies Virus Impairs Viral Replication In Vitro and Neuroinvasion In Vivo,http://dx.doi.org/10.1128/JVI.00280-08,PMC2395145,,,"Herpesviruses specify a ubiquitin-specific protease activity located within their largest tegument protein. Although its biological role is still largely unclear, mutation within the active site abolished deubiquitinating (DUB) activity and decreased virus replication in vitro and in vivo. To further elucidate the role of DUB activity for herpesvirus replication, the conserved active-site cysteine at amino acid position 26 within pUL36 of Pseudorabies virus (PrV) (Suid herpesvirus 1), a neurotropic alphaherpesvirus, was mutated to serine. Whereas one-step growth kinetics of the resulting mutant virus PrV-UL36(C(26)S) were moderately reduced, plaque size was decreased to 62% of that of the wild-type virus. Ultrastructural analysis revealed large accumulations of unenveloped nucleocapsids in the cytoplasm, but incorporation of the tegument protein pUL37 was not abolished. After intranasal infection with PrV-UL36(C(26)S) mice showed survival times two times longer than those of mice infected with wild-type or rescued virus. Thus, the DUB activity is important for PrV replication in vitro and for neuroinvasion in mice.",,"['Böttcher, Sindy', 'Maresch, Christina', 'Granzow, Harald', 'Klupp, Barbara G.', 'Teifke, Jens P.', 'Mettenleiter, Thomas C.']",,,,
,PMC,Cleavage of Group 1 Coronavirus Spike Proteins: How Furin Cleavage Is Traded Off against Heparan Sulfate Binding upon Cell Culture Adaptation,http://dx.doi.org/10.1128/JVI.00074-08,PMC2395124,,,"A longstanding enigmatic feature of the group 1 coronaviruses is the uncleaved phenotype of their spike protein, an exceptional property among class I fusion proteins. Here, however, we show that some group 1 coronavirus spike proteins carry a furin enzyme recognition motif and can actually be cleaved, as demonstrated for a feline coronavirus. Interestingly, this feature can be lost during cell culture adaptation by a single mutation in the cleavage motif; this, however, preserves a heparan sulfate binding motif and renders infection by the virus heparan sulfate dependent. We identified a similar cell culture adaptation for the human coronavirus OC43.",,"['de Haan, C. A. M.', 'Haijema, B. J.', 'Schellen, P.', 'Schreur, P. Wichgers', 'te Lintelo, E.', 'Vennema, H.', 'Rottier, P. J. M.']",,,,
,PMC,Itinerant exosomes: emerging roles in cell and tissue polarity,http://dx.doi.org/10.1016/j.tcb.2008.03.002,PMC3754907,,,"Cells use secreted signals (e.g. chemokines and growth factors) and sophisticated vehicles such as argosomes, cytonemes, tunneling nanotubes and exosomes to relay important information to other cells, often over large distances. Exosomes, 30–100-nm intraluminal vesicles of multivesicular bodies (MVB) released upon exocytic fusion of the MVB with the plasma membrane, are increasingly recognized as a novel mode of cell-independent communication. Exosomes have been shown to function in antigen presentation and tumor metastasis, and in transmitting infectious agents. However, little is known about the biogenesis and function of exosomes in polarized cells. In this review, we discuss new evidence suggesting that exosomes participate in the transport of morphogens and RNA, and thus influence cell polarity and developmental patterning of tissues.",,"['Lakkaraju, Aparna', 'Rodriguez-Boulan, Enrique']",,,,
,PMC,West Nile Virus Entry Requires Cholesterol-Rich Membrane Microdomains and Is Independent of αvβ3 Integrin,http://dx.doi.org/10.1128/JVI.00008-08,PMC2395215,,,"West Nile virus (WNV) has been the leading cause of viral encephalitis in the United States since 1999. The endocytic processes involved in the internalization of infectious WNV by various cell types are not well characterized, and the involvement of cholesterol-rich membrane microdomains, or lipid rafts, in the life cycle of WNV has not been investigated previously. In this study, we found that the depletion of cellular cholesterol levels by brief treatment with methyl-β-cyclodextrin resulted in a 100-fold reduction of the titers of infectious WNV released into the culture supernatant, as well as a reduction in the number of WNV genome copies in the cholesterol-depleted cells. The addition of exogenous cholesterol to cholesterol-depleted cells reversed this effect. Cholesterol depletion postinfection did not affect WNV growth, suggesting that the effect occurs at the level of WNV entry. We also showed that while WNV entry did not require αvβ3 integrin and focal adhesion kinase, WNV particles failed to be internalized by cholesterol-depleted cells. Finally, we showed the colocalization of the WNV envelope protein and cholera toxin B, which is internalized in a lipid raft-dependent pathway, in microdomain clusters at the plasma membrane. These data suggest that WNV utilizes lipid rafts during initial stages of internalization and that the lipid rafts may contain a factor(s) that may enhance WNV endocytosis.",,"['Medigeshi, Guruprasad R.', 'Hirsch, Alec J.', 'Streblow, Daniel N.', 'Nikolich-Zugich, Janko', 'Nelson, Jay A.']",,,,
,PMC,Demyelinating and Nondemyelinating Strains of Mouse Hepatitis Virus Differ in Their Neural Cell Tropism,http://dx.doi.org/10.1128/JVI.01488-07,PMC2395180,,,"Some strains of mouse hepatitis virus (MHV) can induce chronic inflammatory demyelination in mice that mimics certain pathological features of multiple sclerosis. We have examined neural cell tropism of demyelinating and nondemyelinating strains of MHV in order to determine whether central nervous system (CNS) cell tropism plays a role in demyelination. Previous studies demonstrated that recombinant MHV strains, isogenic other than for the spike gene, differ in the extent of neurovirulence and the ability to induce demyelination. Here we demonstrate that these strains also differ in their abilities to infect a particular cell type(s) in the brain. Furthermore, there is a correlation between the differential localization of viral antigen in spinal cord gray matter and that in white matter during acute infection and the ability to induce demyelination later on. Viral antigen from demyelinating strains is detected initially in both gray and white matter, with subsequent localization to white matter of the spinal cord, whereas viral antigen localization of nondemyelinating strains is restricted mainly to gray matter. This observation suggests that the localization of viral antigen to white matter during the acute stage of infection is essential for the induction of chronic demyelination. Overall, these observations suggest that isogenic demyelinating and nondemyelinating strains of MHV, differing in the spike protein expressed, infect neurons and glial cells in different proportions and that differential tropism to a particular CNS cell type may play a significant role in mediating the onset and mechanisms of demyelination.",,"['Das Sarma, Jayasri', 'Iacono, Kathryn', 'Gard, Lilli', 'Marek, Ryan', 'Kenyon, Lawrence C.', 'Koval, Michael', 'Weiss, Susan R.']",,,,
,PMC,"A Novel Mutation in Murine Hepatitis Virus nsp5, the Viral 3C-Like Proteinase, Causes Temperature-Sensitive Defects in Viral Growth and Protein Processing",http://dx.doi.org/10.1128/JVI.00203-08,PMC2395152,,,"Sequencing and reversion analysis of murine hepatitis virus (MHV) temperature-sensitive (ts) viruses has identified putative ts mutations in the replicase nonstructural proteins (nsp's) of these coronaviruses. In this study, reverse transcriptase PCR sequencing of the RNA genome of an isolate of the MHV ts virus Alb ts6, referred to as Alb/ts/nsp5/V148A, identified a putative ts mutation in nsp5 (T10651C, Val148Ala), the viral 3C-like proteinase (3CLpro). The introduction of the T10651C mutation into the infectious MHV clone resulted in the recovery of a mutant virus, the nsp5/V148A virus, that demonstrated reduced growth and nsp5 proteinase activity identical to that of Alb/ts/nsp5/V148A at the nonpermissive temperature. Sequence analysis of 40°C revertants of Alb/ts/nsp5/V148A identified primary reversion to Ala148Val in nsp5, as well as two independent second-site mutations resulting in Ser133Asn and His134Tyr substitutions in nsp5. The introduction of the Ser133Asn or His134Tyr substitution into the cloned nsp5/V148A mutant virus background resulted in the recovery of viruses with increased growth fitness and the partial restoration of nsp5 activity at the nonpermissive temperature. Modeling of the nsp5 structure of Alb/ts/nsp5/V148A predicted that the Val148Ala mutation alters residue 148 interactions with residues of the substrate binding S1 subsite of the nsp5 active-site cavity. This study identifies novel residues in nsp5 that may be important for regulating substrate specificity and nsp5 proteinase activity.",,"['Sparks, Jennifer S.', 'Donaldson, Eric F.', 'Lu, Xiaotao', 'Baric, Ralph S.', 'Denison, Mark R.']",,,,
,PMC,WHO at 60: Snapshots From Its First Six Decades,http://dx.doi.org/10.2105/AJPH.2007.132449,PMC2426911,,,,,"['Fee, Elizabeth', 'Cueto, Marcos', 'Brown, Theodore M.']",,,,
,PMC,Respiratory Viruses Other than Influenza Virus: Impact and Therapeutic Advances,http://dx.doi.org/10.1128/CMR.00045-07,PMC2292575,,,"Summary: Though several antivirals have been developed and marketed to treat influenza virus infections, the development of antiviral agents with clinical activity against other respiratory viruses has been more problematic. Here we review the epidemiology of respiratory viral infections in immunocompetent and immunocompromised hosts, examine the evidence surrounding the currently available antivirals for respiratory viral infections other than influenza, highlight those that are in the pipeline, and discuss the hurdles for development of such agents.",,"['Nichols, W. Garrett', 'Peck Campbell, Angela J.', 'Boeckh, Michael']",,,,
,PMC,Immunologists: What are These People Talking About?,http://dx.doi.org/10.3325/cmj.2008.2.272,PMC2359889,,,,,"Calisher, Charles H.",,,,
,PMC,Pneumonia research to reduce childhood mortality in the developing world,http://dx.doi.org/10.1172/JCI33947,PMC2276784,,,"Pneumonia is an illness, usually caused by infection, in which the lungs become inflamed and congested, reducing oxygen exchange and leading to cough and breathlessness. It affects individuals of all ages but occurs most frequently in children and the elderly. Among children, pneumonia is the most common cause of death worldwide. Historically, in developed countries, deaths from pneumonia have been reduced by improvements in living conditions, air quality, and nutrition. In the developing world today, many deaths from pneumonia are also preventable by immunization or access to simple, effective treatments. However, as we highlight here, there are critical gaps in our understanding of the epidemiology, etiology, and pathophysiology of pneumonia that, if filled, could accelerate the control of pneumonia and reduce early childhood mortality.",,"['Scott, J. Anthony G.', 'Brooks, W. Abdullah', 'Peiris, J.S. Malik', 'Holtzman, Douglas', 'Mulhollan, E. Kim']",,,,
,PMC,Evaluation of real-time RT-PCR for the quantification of FCoV shedding in the faeces of domestic cats,http://dx.doi.org/10.1016/j.jfms.2007.10.010,PMC2582154,18243744,NO-CC CODE,"Faecal samples were taken from cats living in multi-cat households with endemic feline coronavirus (FCoV) infection. Total RNA was extracted from faecal suspensions and FCoV RNA was quantified using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. The real-time RT-PCR threshold cycle (C(T)) values were consistently high suggesting that the samples contained very little viral RNA. However, experiments in which RNA extracted from FCoV-infected cell culture supernatants was combined with RNA extracted from faecal suspensions revealed the presence of faecal factors that significantly inhibited the reverse transcription reaction. Consequently, three methods of RNA extraction were investigated and RNA dilution was undertaken to investigate whether the effects of the faecal inhibitors could be reduced. Our results show that using the QIAgen RNA mini kit for RNA extraction and dilution of the RNA samples helps to reduce the inhibitory effects. However, because the extent of the inhibitory effects varied between faecal samples, accurate quantification proved difficult. We, therefore, conclude that although real-time RT-PCR provides an excellent method for detecting the presence of viral shedding, quantification of FCoV RNA in faecal material has to take into account the possible effects of RT-PCR inhibitors. It is, therefore, essential that all new assays, and the methods of sample preparation, are carefully evaluated before being used in a clinical setting.",2008 Apr,"['Dye, Charlotte', 'Helps, Christopher R.', 'Siddell, Stuart G.']",J Feline Med Surg,,,
,PMC,An Increase in Herpes Simplex Virus Type 1 in the Anterior Segment of the Eye is Linked to a Deficiency in NK Cell Infiltration in Mice Deficient in CXCR3,http://dx.doi.org/10.1089/jir.2007.0110,PMC2396780,,,"In response to ocular herpes simplex virus type 1 (HSV-1) infection in mice a rapid induction or increase in the local expression of chemokines including CXCL10 is found. The present study investigated the role of the receptor for CXCL10, CXCR3, in the host response to corneal HSV-1 infection. Mice deficient in CXCR3 (CXCR3−/ −) were found to have an increase in infectious virus in the anterior segment of the eye by day 7 post infection. Coinciding with the increase, selective chemokines including CCL2, CCL3, CCL5, CXCL9, and CXCL10 were elevated in the anterior segment of the HSV-1-infected CXCR3−/− mice. In contrast, there was a time-dependent reduction in the recruitment of NK cells (NK1.1(+)CD3(−)) into the anterior segment of CXCR3 −/− mice. A reduction in NK cells residing in the anterior segment of mice following anti-asialo GM1 antibody treatment resulted in an increase in infectious virus. No other leukocyte populations infiltrating the tissue were modified in the absence of CXCR3. Collectively, the loss of CXCR3 expression specifically reduces NK cell mobilization into the cornea in response to HSV-1.",,"['Carr, Daniel J.J.', 'Wuest, Todd', 'Ash, John']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00383-08,PMC2293014,,,,,,,,,
,PMC,KnotSeeker: Heuristic pseudoknot detection in long RNA sequences,http://dx.doi.org/10.1261/rna.968808,PMC2271355,,,"Pseudoknots are folded structures in RNA molecules that perform essential functions as part of cellular transcription machinery and regulatory processes. The prediction of these structures in RNA molecules has important implications in antiviral drug design. It has been shown that the prediction of pseudoknots is an NP-complete problem. Practical structure prediction algorithms based on free energy minimization employ a restricted problem class and dynamic programming. However, these algorithms are computationally very expensive, and their accuracy deteriorates if the input sequence containing the pseudoknot is too long. Heuristic methods can be more efficient, but do not guarantee an optimal solution in regards to the minimum free energy model. We present KnotSeeker, a new heuristic algorithm for the detection of pseudoknots in RNA sequences as a preliminary step for structure prediction. Our method uses a hybrid sequence matching and free energy minimization approach to perform a screening of the primary sequence. We select short sequence fragments as possible candidates that may contain pseudoknots and verify them by using an existing dynamic programming algorithm and a minimum weight independent set calculation. KnotSeeker is significantly more accurate in detecting pseudoknots compared to other common methods as reported in the literature. It is very efficient and therefore a practical tool, especially for long sequences. The algorithm has been implemented in Python and it also uses C/C++ code from several other known techniques. The code is available from http://www.csse.uwa.edu.au/∼datta/pseudoknot.",,"['Sperschneider, Jana', 'Datta, Amitava']",,,,
,PMC,Persistent Replication of Severe Acute Respiratory Syndrome Coronavirus in Human Tubular Kidney Cells Selects for Adaptive Mutations in the Membrane Protein,http://dx.doi.org/10.1128/JVI.00096-08,PMC2395189,,,"Severe acute respiratory syndrome (SARS) is a systemic disease characterized by both lung pathology and widespread extrapulmonary virus dissemination causing multiple organ injuries. In this regard, renal dysfunction is an ominous sign in patients with SARS. Indeed, clusters of SARS coronavirus (SARS-CoV) particles have been detected in the cytoplasm of renal tubular epithelial cells in postmortem studies, explaining the presence of infectious virus in the urine of SARS patients. In order to investigate the potential SARS-CoV kidney tropism, we have evaluated the susceptibility of human renal cells of tubular and glomerular origin to in vitro SARS-CoV infection. Immortalized cultures of differentiated proximal tubular epithelial cells (PTEC), glomerular mesangial cells (MC), and glomerular epithelial cells (podocytes) were found to express the SARS-CoV receptor angiotensin-converting enzyme 2 on their surface. Productive infection, however, occurred only in PTEC but not in glomerular cells. A transient infection with poor virus production was observed in MC, whereas podocytes were not permissive to SARS-CoV infection. In contrast to the cytopathic infection of the Vero E6 cell line, SARS-CoV did not cause overt cytopathic effects in PTEC or MC. Of interest, PTEC, but not MC, maintained stable levels of SARS-CoV production in serial subcultures, suggesting a persistent state of infection. In this regard, a SARS-CoV variant with increased replication capacity in PTEC was selected after four serial subculture passages. This SARS-CoV variant acquired a single nonconservative amino acid change from glutamic acid (E) to alanine (A) at position 11 in the viral membrane (M) protein. The E11A point mutation was sufficient for enhanced SARS-CoV replication and persistence in PTEC when introduced in a SARS-CoV recombinant infectious clone. These findings indicate that human PTEC may represent a site of SARS-CoV productive and persistent replication favoring the emergence of viral variants with increased replication capacity, at least in these kidney cells.",,"['Pacciarini, Filippo', 'Ghezzi, Silvia', 'Canducci, Filippo', 'Sims, Amy', 'Sampaolo, Michela', 'Ferioli, Elena', 'Clementi, Massimo', 'Poli, Guido', 'Conaldi, Pier Giulio', 'Baric, Ralph', 'Vicenzi, Elisa']",,,,
,PMC,Proteomics Analysis Unravels the Functional Repertoire of Coronavirus Nonstructural Protein 3,http://dx.doi.org/10.1128/JVI.02631-07,PMC2395186,,,"Severe acute respiratory syndrome (SARS) coronavirus infection and growth are dependent on initiating signaling and enzyme actions upon viral entry into the host cell. Proteins packaged during virus assembly may subsequently form the first line of attack and host manipulation upon infection. A complete characterization of virion components is therefore important to understanding the dynamics of early stages of infection. Mass spectrometry and kinase profiling techniques identified nearly 200 incorporated host and viral proteins. We used published interaction data to identify hubs of connectivity with potential significance for virion formation. Surprisingly, the hub with the most potential connections was not the viral M protein but the nonstructural protein 3 (nsp3), which is one of the novel virion components identified by mass spectrometry. Based on new experimental data and a bioinformatics analysis across the Coronaviridae, we propose a higher-resolution functional domain architecture for nsp3 that determines the interaction capacity of this protein. Using recombinant protein domains expressed in Escherichia coli, we identified two additional RNA-binding domains of nsp3. One of these domains is located within the previously described SARS-unique domain, and there is a nucleic acid chaperone-like domain located immediately downstream of the papain-like proteinase domain. We also identified a novel cysteine-coordinated metal ion-binding domain. Analyses of interdomain interactions and provisional functional annotation of the remaining, so-far-uncharacterized domains are presented. Overall, the ensemble of data surveyed here paint a more complete picture of nsp3 as a conserved component of the viral protein processing machinery, which is intimately associated with viral RNA in its role as a virion component.",,"['Neuman, Benjamin W.', 'Joseph, Jeremiah S.', 'Saikatendu, Kumar S.', 'Serrano, Pedro', 'Chatterjee, Amarnath', 'Johnson, Margaret A.', 'Liao, Lujian', 'Klaus, Joseph P.', 'Yates, John R.', 'Wüthrich, Kurt', 'Stevens, Raymond C.', 'Buchmeier, Michael J.', 'Kuhn, Peter']",,,,
,PMC,Regulation of the proapoptotic factor Bax by Ku70-dependent deubiquitylation,http://dx.doi.org/10.1073/pnas.0706700105,PMC2278173,,,"The DNA end-joining protein Ku70 is one of several proteins that inhibit apoptosis by sequestering the proapoptotic factor Bax from the mitochondria. However, the molecular mechanism underlying Ku70-dependent inhibition of Bax is not fully understood. Here, we show that the absence of Ku70 results in the accumulation of ubiquitylated Bax. Under normal growth conditions, Bax ubiquitylation promotes its degradation. Upon induction of apoptosis in wild-type cells, a significant reduction in the levels of ubiquitylated Bax was observed, whereas in Ku70(−/−) cells, the ubiquitylated Bax was robustly accumulated. Addition of recombinant Ku70 into a protein extract of Ku70(−/−) cells resulted in a decrease in the levels of ubiquitylated Bax, even in the presence of proteasome inhibitors. Moreover, an in vitro deubiquitylation assay demonstrated that recombinant Ku70 hydrolyzed polyubiquitin chains into monoubiquitin units. Thus, Ku70 regulates apoptosis by sequestering Bax from the mitochondria and mediating Bax deubiquitylation. These results shed light on the role of proteasome inhibitors as tumor suppressors.",,"['Amsel, Avigail D.', 'Rathaus, Moran', 'Kronman, Noam', 'Cohen, Haim Y.']",,,,
,PMC,Hong Kong closes all primary schools in flu outbreak,http://dx.doi.org/10.1136/bmj.39520.678009.DB,PMC2270971,,,,,"Parry, Jane",,,,
,PMC,Survival of Influenza Virus on Banknotes,http://dx.doi.org/10.1128/AEM.00076-08,PMC2394922,,,"Successful control of a viral disease requires knowledge of the different vectors that could promote its transmission among hosts. We assessed the survival of human influenza viruses on banknotes given that billions of these notes are exchanged daily worldwide. Banknotes were experimentally contaminated with representative influenza virus subtypes at various concentrations, and survival was tested after different time periods. Influenza A viruses tested by cell culture survived up to 3 days when they were inoculated at high concentrations. The same inoculum in the presence of respiratory mucus showed a striking increase in survival time (up to 17 days). Similarly, B/Hong Kong/335/2001 virus was still infectious after 1 day when it was mixed with respiratory mucus. When nasopharyngeal secretions of naturally infected children were used, influenza virus survived for at least 48 h in one-third of the cases. The unexpected stability of influenza virus in this nonbiological environment suggests that unusual environmental contamination should be considered in the setting of pandemic preparedness.",,"['Thomas, Yves', 'Vogel, Guido', 'Wunderli, Werner', 'Suter, Patricia', 'Witschi, Mark', 'Koch, Daniel', 'Tapparel, Caroline', 'Kaiser, Laurent']",,,,
,PMC,N-linked glycosylation and its impact on the electrophoretic mobility and function of the human Proton-Coupled Folate Transporter (HsPCFT),http://dx.doi.org/10.1016/j.bbamem.2008.03.009,PMC2762823,,,"The human proton-coupled folate transporter (HsPCFT, SLC46A1) mediates intestinal absorption of folates and transport of folates into the liver, brain and other tissues. On Western blot, HsPCFT migrates as a broad band (∼55 kDa), higher than predicted (∼50 kDa) in cell lines. Western blot analysis required that membrane preparations not be incubated in the loading buffer above 50°C to avoid aggregation of the protein. Treatment of membrane fractions from HsPCFT-transfected HeLa cells with peptidyl N-glycanase F, or cells with tunicamycin, resulted in conversion to a ∼35 kDa species. Substitution of asparagine residues of two canonical glycosylation sites to glutamine, individually, yielded a ∼ 47 kDa protein; substitution of both sites gave a smaller (∼35 kDa) protein. Single mutants retained full transport activity; the double mutant retained a majority of activity. Transport function and molecular size were unchanged when the double-mutant was hemagglutinin (HA) tagged at either the NH(2) or COOH terminus and probed with an anti-HA antibody excluding degradation of the deglycosylated protein. Wild-type or deglycosylated HsPCFT HA, tagged at amino or carboxyl termini, could only be visualized on the plasma membrane when HeLa cells were first permeabilized, consistent with the intracellular location of these domains.",,"['Unal, Ersin Selcuk', 'Zhao, Rongbao', 'Qiu, Andong', 'Goldman, I. David']",,,,
,PMC,Heritable Thrombophilia-Hypofibrinolysis and Osteonecrosis of the Femoral Head,http://dx.doi.org/10.1007/s11999-008-0148-0,PMC2311469,,,"We hypothesized that inherited thrombophilia and hypofibrinolysis were risk factors for osteonecrosis of the femoral head. We compared measures of thrombophilia and hypofibrinolysis in referred new adult patients with idiopathic osteonecrosis (n = 71) or secondary osteonecrosis (n = 62) with the same measures in sex- and race-matched healthy control subjects. Heritable thrombophilic Factor VIII and hypofibrinolytic Lp(a) were more frequently high in the 71 patients with idiopathic osteonecrosis than in control subjects. High Factor VIII, Factor V Leiden heterozygosity, and resistance to activated protein C, all heritable thrombophilias, were more frequently present in the 62 patients with secondary osteonecrosis than in control subjects. Our data suggest inherited thrombophilia and hypofibrinolysis are risk factors for both idiopathic and secondary osteonecrosis of the head of the femur. Level of Evidence: Level IV, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.",,"['Glueck, Charles J.', 'Freiberg, Richard A.', 'Wang, Ping']",,,,
,PMC,Sex-Dependent Differences in Plasma Cytokine Responses to Hantavirus Infection,http://dx.doi.org/10.1128/CVI.00035-08,PMC2394832,,,"There are often sex differences in susceptibility to infectious diseases and in level of mortality after infection. These differences probably stem from sex-related abilities to mount proper or unwanted immune responses against an infectious agent. We report that hantavirus-infected female patients show significantly higher plasma levels of interleukin-9 (IL-9), fibroblast growth factor 2, and granulocyte-macrophage colony-stimulating factor and lower levels of IL-8 and gamma interferon-induced protein 10 than male patients. The results demonstrate that a virus infection can induce sex-dependent differences in acute immune responses in humans. This finding may, at least partly, explain the observed sex differences in susceptibility to infectious diseases and in mortality following infection.",,"['Klingström, Jonas', 'Lindgren, Therese', 'Ahlm, Clas']",,,,
,PMC,Identification of a Novel Coronavirus from a Beluga Whale by Using a Panviral Microarray,http://dx.doi.org/10.1128/JVI.02722-07,PMC2346750,,,"The emergence of viruses such as severe acute respiratory syndrome coronavirus and Nipah virus has underscored the role of animal reservoirs in human disease and the need for reservoir surveillance. Here, we used a panviral DNA microarray to investigate the death of a captive beluga whale in an aquatic park. A highly divergent coronavirus, tentatively named coronavirus SW1, was identified in liver tissue from the deceased whale. Subsequently, the entire genome of SW1 was sequenced, yielding a genome of 31,686 nucleotides. Phylogenetic analysis revealed SW1 to be a novel virus distantly related to but most similar to group III coronaviruses.",,"['Mihindukulasuriya, Kathie A.', 'Wu, Guang', 'St. Leger, Judy', 'Nordhausen, Robert W.', 'Wang, David']",,,,
,PMC,Homelessness and the Response to Emerging Infectious Disease Outbreaks: Lessons from SARS,http://dx.doi.org/10.1007/s11524-008-9270-2,PMC2329752,,,"During the 2003 severe acute respiratory syndrome (SARS) outbreak in Toronto, the potential introduction of SARS into the homeless population was a serious concern. Although no homeless individual in Toronto contracted SARS, the outbreak highlighted the need to develop an outbreak preparedness plan that accounts for unique issues related to homeless people. We conducted key informant interviews with homeless service providers and public health officials (n = 17) and identified challenges specific to the homeless population in the areas of communication, infection control, isolation and quarantine, and resource allocation. Planning for future outbreaks should take into account the need to (1) develop systems that enable rapid two-way communication between public health officials and homeless service providers, (2) ensure that homeless service providers have access to infection control supplies and staff training, (3) prepare for possible homeless shelter closures due to staff shortages or high attack rates among clients, and (4) plan for where and how clinically ill homeless individuals will be isolated and treated. The Toronto SARS experience provided insights that are relevant to response planning for future outbreaks in cities with substantial numbers of homeless individuals.",,"['Leung, Cheryl S.', 'Ho, Minnie M.', 'Kiss, Alex', 'Gundlapalli, Adi V.', 'Hwang, Stephen W.']",,,,
,PMC,Epithelial Cell Apoptosis and Neutrophil Recruitment in Acute Lung Injury—A Unifying Hypothesis? What We Have Learned from Small Interfering RNAs,http://dx.doi.org/10.2119/2008-00011.Perl,PMC2274893,,,"In spite of protective ventilatory strategies, Acute Lung Injury (ALI) remains associated with high morbidity and mortality. One reason for the lack of therapeutic options might be that ALI is a co-morbid event associated with a diverse family of diseases and, thus, may be the result of distinct pathological processes. Among them, activated neutrophil- (PMN-) induced tissue injury and epithelial cell apoptosis mediated lung damage represent two potentially important candidate pathomechanisms that have been put forward. Several approaches have been undertaken to test these hypotheses, with substantial success in the treatment of experimental forms of ALI. With this in mind, we will summarize these two current hypotheses of ALI briefly, emphasizing the role of apoptosis in regulating PMN and/or lung epithelial cell responses. In addition, the contribution that Fas-mediated inflammation may play as a potential biological link between lung cell apoptosis and PMN recruitment will be considered, as well as the in vivo application of small interfering RNA (siRNA) as a novel approach to the inhibition of ALI and its therapeutic implications.",,"['Perl, Mario', 'Lomas-Neira, Joanne', 'Chung, Chun-Shiang', 'Ayala, Alfred']",,,,
,PMC,Early growth response-1 protein is induced by JC virus infection and binds and regulates the JC virus promoter,http://dx.doi.org/10.1016/j.virol.2008.02.021,PMC2632587,,,"JC virus (JCV) is a human polyomavirus that can emerge from a latent state to cause the cytolytic destruction of oligodendrocytes in the brain resulting in the fatal demyelinating disease, Progressive Multifocal Leukoencephalopathy (PML). Previous studies described a cis-acting transcriptional regulatory element in the JCV non-coding control region (NCCR) that is involved in the response of JCV to cytokines. This consists of a 23 base pair GGA/C rich sequence (GRS) near the replication origin (5112 to +4) that contains potential binding sites for Sp1 and Egr-1. Gel shift analysis showed that Egr-1, but not Sp1, bound to GRS. Evidence is presented that the GRS gel shift seen on cellular stimulation is due to Egr-1. Thus, TPA-induced GRS gel shift could be blocked by antibody to Egr-1. Further, the TPA-induced GRS DNA/protein complex was isolated and found to contain Egr-1 by Western blot. No other Egr-1 sites were found in the JCV NCCR. Functionally, Egr-1 was found to stimulate transcription of JCV late promoter but not early promoter reporter constructs. Mutation of the Egr-1 site abrogated Egr-1 binding and virus with the mutated Egr-1 site showed markedly reduced VP1 expression and DNA replication. Infection of primary astrocytes by wild-type JCV induced Egr-1 nuclear expression that was maximal at 5–10 days post-infection. Finally, upregulation of Egr-1 was detected in PML by immunohistochemistry. These data suggest that Egr-1 induction may be important in the life cycle of JCV and PML pathogenesis.",,"['Romagnoli, Luca', 'Sariyer, Ilker K.', 'Tung, Jacqueline', 'Feliciano, Mariha', 'Sawaya, Bassel E.', 'Valle, Luis Del', 'Ferrante, Pasquale', 'Khalili, Kamel', 'Safak, Mahmut', 'White, Martyn K.']",,,,
,PMC,Detection and significance of serum protein markers of small‐cell lung cancer,http://dx.doi.org/10.1002/jcla.20230,PMC6649243,,,"Currently, no satisfactory biomarkers are available to screen for small‐cell lung cancer (SCLC). We applied a surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry (SELDI‐TOF MS) ProteinChip system to detect 150 serum samples (including 54 SCLC patients, 24 non‐small cell lung cancer [NSCLC] patients, 32 pneumonia patients, and 40 healthy individuals). The spectra data were analyzed by support vector machine (SVM) and potential biomarkers were chosen for the system training and used to construct diagnostic model. Pattern 1, constructed of four protein peaks with mass/charge (m/z) of 4,293 Da, 4,612 Da, 6,455 Da, and 7,582 Da, separated SCLC patients from the healthy individuals with a sensitivity of 88.9% and a specificity of 85.7%. This pattern performed significantly better than the current marker, neuron‐specific enolase (NSE) (P<0.05). Pattern 2, constructed of protein peaks with mass/charge (m/z) of 2,764 Da and 1,7368 Da, separated SCLC from pneumonia with a sensitivity of 88.9% and a specificity of 91.7%. Pattern 3, constructed of another three protein peaks with m/z of 3,912 Da, 7,562 Da, and 13,777 Da, separated SCLC from NSCLC. The sensitivity and specificity were 83.3% and 75.0%, respectively. These results suggested that SELDI‐TOF MS combined with support vector machine yields significantly higher sensitivity and specificity for the detection of serum protein of SCLC. J. Clin. Lab. Anal. 22:131–137, 2008. © 2008 Wiley‐Liss, Inc.",,"['Han, Mingyong', 'Liu, Qi', 'Yu, Jiekai', 'Zheng, Shu']",,,,
,PMC,Viral upper respiratory tract infection and otitis media complication in young children,http://dx.doi.org/10.1086/528685,PMC2744371,,,"BACKGROUND: The common cold or upper respiratory infection (URI) is highly prevalent in young children and often results in otitis media (OM). Incidence and characteristics of OM complicating URI by specific viruses have not been well studied. METHODS: We performed a prospective, longitudinal, cohort study of 294 healthy children (6 mos. to 3 yrs. of age). Each child was followed for 1 year for the occurrences of URI and acute otitis media (AOM) and otitis media with effusion (OME) complicating URI by specific viruses. RESULTS: There were 1295 URI episodes (5.06 episodes/child-year) and 440 AOM episodes (1.72 episodes/child-year) documented. Virus studies were performed in 864 URI episodes; 63% were virus positive. Rhinovirus and adenovirus were most commonly detected during URI. The overall incidence of OM complicating URI was 61%, including 37% AOM and 24% OME. Young age was the most important predictor for AOM complicating URI. AOM occurred in about half of children with URI associated with adenovirus, respiratory syncytial virus (RSV), and coronavirus, and about one-third of those with influenza, parainfluenza, enterovirus and rhinovirus. CONCLUSIONS: More than 60% of symptomatic URI episodes in young children were complicated by AOM and/or OME. Young age and specific virus types were predictors of AOM complicating URI. Preventive strategy for OM should be through preventing viral URI in young children. The strategy may be more effective if the priority is given to development of ways to prevent URI associated with adenovirus and RSV.",,"['Chonmaitree, Tasnee', 'Revai, Krystal', 'Grady, James J.', 'Clos, Audra', 'Patel, Janak A.', 'Nair, Sangeeta', 'Fan, Jiang', 'Henrickson, Kelly J.']",,,,
,PMC,Prime-boost vaccination with a combination of proteosome-degradable and wild-type forms of two influenza proteins leads to augmented CTL response,http://dx.doi.org/10.1016/j.vaccine.2008.02.050,PMC2440663,,,"Targeting viral antigens for proteosomal degradation has previously been proposed as a means for immunogenicity augmentation. However, utilization of modified unstable antigens may be insufficient for potent T-cell cross-presentation by APCs, a mechanism that requires high levels of the antigenic protein. Therefore, we hypothesized that a recombinant vaccine utilizing a combination of proteosome-sensitive and proteosome-resistant versions of an antigen in a prime/boost regimen may provide the most efficient CTL response. To address this hypothesis, we utilized conserved proteosome-resistant influenza A virus proteins M1 and NS1. Unstable versions of these polypeptides were constructed by destroying their 3-D structure via truncations or short insertions into predicted alpha-helical structures. These modified polypeptides were stabilized in the presence of the proteosome inhibitor MG132, strongly suggesting that they are degraded via a ubiquitin-proteosome pathway. Importantly, with both M1 and NS1antigens, homologous DNA vaccination with a mixture of unstable and proteosome-resistant wt forms of these proteins resulted in significantly higher CTL activity than vaccination with either wt or degradable forms. The most dramatic effect was seen with NS1, where homologous immunization with a mixture of these two forms was the only regimen that produced a notable elevation of CTL response, compared to vaccination with the wt NS1. Additionally, for M1 protein, heterologous vaccination utilizing the unstable form as prime and wild type form as boost, demonstrated significant augmentation of the CTL response. These data indicate that combining proteosome-sensitive and proteosome-resistant forms of an antigen during vaccination is advantageous.",,"['Ilyinskii, P. O.', 'Meriin, A. B.', 'Gabai, V. L.', 'Zhirnov, O. P.', 'Thoidis, G.', 'Shneider, A. M.']",,,,
,PMC,Role of the Akt pathway in mRNA translation of interferon-stimulated genes,http://dx.doi.org/10.1073/pnas.0710907105,PMC2290753,,,"Multiple signaling pathways are engaged by the type I and II IFN receptors, but their specific roles and possible coordination in the generation of IFN-mediated biological responses remain unknown. We provide evidence that activation of Akt kinases is required for IFN-inducible engagement of the mTOR/p70 S6 kinase pathway. Our data establish that Akt activity is essential for up-regulation of key IFN-α- and IFN-γ-inducible proteins, which have important functional consequences in the induction of IFN responses. Such effects of the Akt pathway are unrelated to regulatory activities on IFN-dependent STAT phosphorylation/activation or transcriptional regulation. By contrast, they reflect regulatory activities on mRNA translation via direct control of the mTOR pathway. In studies using Akt1 and Akt2 double knockout cells, we found that the absence of Akt kinases results in dramatic reduction in IFN-induced antiviral responses, establishing a critical role of the Akt pathway in IFN signaling. Thus, activation of the Akt pathway by the IFN receptors complements the function of IFN-activated JAK–STAT pathways, by allowing mRNA translation of IFN-stimulated genes and, ultimately, the induction of the biological effects of IFNs.",,"['Kaur, Surinder', 'Sassano, Antonella', 'Dolniak, Blazej', 'Joshi, Sonali', 'Majchrzak-Kita, Beata', 'Baker, Darren P.', 'Hay, Nissim', 'Fish, Eleanor N.', 'Platanias, Leonidas C.']",,,,
,PMC,Proteomics and genomics: Perspectives on drug and target discovery,http://dx.doi.org/10.1016/j.cbpa.2008.02.016,PMC2386992,,,,,"['Ahn, Natalie G.', 'Wang, Andrew H.-J.']",,,,
,PMC,Predicting ribosomal frameshifting efficiency,http://dx.doi.org/10.1088/1478-3975/5/1/016002,PMC2442619,,,"Many retroviruses use −1 ribosomal frameshifting as part of the mechanism in translational control of viral protein synthesis. Quantitative prediction of the efficiency of −1 frameshifting is crucial for understanding the viral gene expression. Here we investigate the free energy landscape for a minimal −1 programmed ribosomal frameshifting machinery, including the codon–anticodon base pairs at the slippery site, the downstream messenger RNA structure and the spacer between the slippery site and the downstream structure. The free energy landscape analysis leads to a quantitative relationship between the frameshifting efficiency and the tension force generated during the movement of codon–anticodon complexes, which may occur in the A/T to A/A accommodation process or the translocation process. The analysis shows no consistent correlation between frameshifting efficiency and global stability of the downstream mRNA structure.",,"['Cao, Song', 'Chen, Shi-Jie']",,,,
,PMC,Following translation by single ribosomes one codon at a time,http://dx.doi.org/10.1038/nature06716,PMC2556548,,,"We have followed individual ribosomes as they translate single messenger RNA hairpins tethered by the ends to optical tweezers. Here we reveal that translation occurs through successive translocation-and-pause cycles. The distribution of pause lengths, with a median of 2.8 s, indicates that at least two rate-determining processes control each pause. Each translocation step measures three bases—one codon—and occurs in less than 0.1 s. Analysis of the times required for translocation reveals, surprisingly, that there are three substeps in each step. Pause lengths, and thus the overall rate of translation, depend on the secondary structure of the mRNA; the applied force destabilizes secondary structure and decreases pause durations, but does not affect translocation times. Translocation and RNA unwinding are strictly coupled ribosomal functions.",,"['Wen, Jin-Der', 'Lancaster, Laura', 'Hodges, Courtney', 'Zeri, Ana-Carolina', 'Yoshimura, Shige H.', 'Noller, Harry F.', 'Bustamante, Carlos', 'Tinoco, Ignacio']",,,,
,PMC,Surveillance of new infectious diseases focuses on wrong areas,http://dx.doi.org/10.1136/bmj.39510.537639.DB,PMC2265316,,,,,"Mayor, Susan",,,,
,PMC,Utility of DNA Microarrays for Detection of Viruses in Acute Respiratory Tract Infections in Children,http://dx.doi.org/10.1016/j.jpeds.2007.12.035,PMC3174048,,,"OBJECTIVE: To assess the utility of a pan-viral DNA microarray platform (Virochip) in the detection of viruses associated with pediatric respiratory tract infections. STUDY DESIGN: The Virochip was compared with conventional direct fluorescent antibody (DFA) and PCR-based testing for the detection of respiratory viruses in 278 consecutive nasopharyngeal aspirate samples from 222 children. RESULTS: The Virochip was superior in performance to DFA, showing a 19% increase in the detection of 7 respiratory viruses included in standard DFA panels, and was similar to virus-specific PCR (sensitivity 85–90%, specificity ≥99%, PPV 94–96%, NPV 97–98%) in the detection of respiratory syncytial virus, influenza A, and rhino-/enteroviruses. The Virochip also detected viruses not routinely tested for or missed by DFA and PCR, as well as double infections and infections in critically ill patients that DFA failed to detect. CONCLUSIONS: Given its favorable sensitivity and specificity profile and expanded spectrum for detection, microarray-based viral testing holds promise for clinical diagnosis of pediatric respiratory tract infections.",,"['Chiu, Charles Y.', 'Urisman, Anatoly', 'Greenhow, Tara L.', 'Rouskin, Silvi', 'Yagi, Shigeo', 'Schnurr, David', 'Wright, Carolyn', 'Drew, W. Lawrence', 'Wang, David', 'Weintrub, Peggy S.', 'DeRisi, Joseph L.', 'Ganem, Don']",,,,
,PMC,Consistent blind protein structure generation from NMR chemical shift data,http://dx.doi.org/10.1073/pnas.0800256105,PMC2290745,,,"Protein NMR chemical shifts are highly sensitive to local structure. A robust protocol is described that exploits this relation for de novo protein structure generation, using as input experimental parameters the (13)C(α), (13)C(β), (13)C′, (15)N, (1)H(α) and (1)H(N) NMR chemical shifts. These shifts are generally available at the early stage of the traditional NMR structure determination process, before the collection and analysis of structural restraints. The chemical shift based structure determination protocol uses an empirically optimized procedure to select protein fragments from the Protein Data Bank, in conjunction with the standard ROSETTA Monte Carlo assembly and relaxation methods. Evaluation of 16 proteins, varying in size from 56 to 129 residues, yielded full-atom models that have 0.7–1.8 Å root mean square deviations for the backbone atoms relative to the experimentally determined x-ray or NMR structures. The strategy also has been successfully applied in a blind manner to nine protein targets with molecular masses up to 15.4 kDa, whose conventional NMR structure determination was conducted in parallel by the Northeast Structural Genomics Consortium. This protocol potentially provides a new direction for high-throughput NMR structure determination.",,"['Shen, Yang', 'Lange, Oliver', 'Delaglio, Frank', 'Rossi, Paolo', 'Aramini, James M.', 'Liu, Gaohua', 'Eletsky, Alexander', 'Wu, Yibing', 'Singarapu, Kiran K.', 'Lemak, Alexander', 'Ignatchenko, Alexandr', 'Arrowsmith, Cheryl H.', 'Szyperski, Thomas', 'Montelione, Gaetano T.', 'Baker, David', 'Bax, Ad']",,,,
,PMC,Dengue virus in Mexican bats,http://dx.doi.org/10.1017/S0950268808000460,PMC2870782,,,"Individuals belonging to five families, 12 genera, and 19 different species of bats from dengue endemic areas in the Gulf and Pacific coasts of Mexico were examined by ELISA, RT–PCR, and for the presence of dengue virus (DV) NS1 protein. Nine individuals from four species were seropositive by ELISA: three insectivorous, Myotis nigricans (four positives/12 examined), Pteronotus parnellii (3/19), and Natalus stramineus (1/4), and one frugivorous Artibeus jamaicensis (1/35) (12·86% seroprevalence in positive species). DV serotype 2 was detected by RT–PCR in four samples from three species (all from the Gulf coast – rainy season): two frugivorous, A. jamaicensis (2/9), and Carollia brevicauda (1/2), and one insectivorous, M. nigricans (1/11). The latter was simultaneously positive for NS1 protein. DV RT–PCR positive animals were all antibody seronegative. M. nigricans showed positive individuals for all three tests. This is the first evidence suggesting the presence of DV in bats from Mexico.",,"['AGUILAR-SETIÉN, Á.', 'ROMERO-ALMARAZ, M.\xa0L.', 'SÁNCHEZ-HERNÁNDEZ, C.', 'FIGUEROA, R.', 'JUÁREZ-PALMA, L.\xa0P.', 'GARCÍA-FLORES, M.\xa0M.', 'VÁZQUEZ-SALINAS, C.', 'SALAS-ROJAS, M.', 'HIDALGO-MARTÍNEZ, A.\xa0C.', 'PIERLÉ, S. AGUILAR', 'GARCÍA-ESTRADA, C.', 'RAMOS, C.']",,,,
,PMC,Exosome Function: From Tumor Immunology to Pathogen Biology,http://dx.doi.org/10.1111/j.1600-0854.2008.00734.x,PMC3636814,,,"Exosomes are the newest family member of ‘bioactive vesicles’ that function to promote intercellular communication. Exosomes are derived from the fusion of multi-vesicular bodies with the plasma membrane and extracellular release of the intraluminal vesicles. Recent studies have focused on the biogenesis and composition of exosomes as well as regulation of exosome release. Exosomes have been shown to be released by cells of hematopoietic and non-hematopoietic origin, yet their function remains enigmatic. Much of the prior work has focused on exosomes as a source of tumor antigens and in presentation of tumor antigens to T cells. However, new studies have shown that exosomes might also promote cell-to-cell spread of infectious agents. Moreover, exosomes isolated from cells infected with various intra-cellular pathogens, including Mycobacterium tuberculosis and Toxoplasma gondii, have been shown to contain microbial components and can promote antigen presentation and macrophage activation, suggesting that exosomes may function in immune surveillance. In this review, we summarize our understanding of exosome biogenesis but focus primarily on new insights into exosome function. We also discuss their possible use as disease biomarkers and vaccine candidates.",,"['Schorey, Jeffrey S.', 'Bhatnagar, Sanchita']",,,,
,PMC,ELISAs USING HUMAN BOCAVIRUS VP2 VIRUS-LIKE PARTICLES FOR DETECTION OF ANTIBODIES AGAINST HBoV,http://dx.doi.org/10.1016/j.jviromet.2007.12.016,PMC2327203,,,"Human bocavirus (HBoV) has been identified worldwide in children with lower respiratory tract infections with an incidence of approximately 2% −11%. The role of HBoV in pathogenesis, however, is largely unknown, and little is known about the epidemiology of the virus. To study the seroepidemiology of HBoV infection, the capsid protein was expressed in insect cells. Expression of the putative major capsid protein VP2 in insect cells led to the formation of virus-like particles exhibiting the typical icosahedral appearance of parvoviruses with a diameter of approximately 20 nm. The expressed particles were used to establish an ELISA method, and serum samples from groups of children of various ages in China were tested for IgG antibodies against HBoV. HBoV antibodies were detected in as high as 36% of healthy children under 9 years. Of children hospitalized with lower respiratory tract infections, 31% were seropositive, and all age groups of these children showed a significantly higher level of HBoV IgG antibody than their healthy counterparts. When divided into age cohorts, results showed that more than 48% of healthy children had seroconverted by age of 4. Thus, HBoV appears to be a common infection in children. The potential pathogenesis of this virus, especially its role in lower respiratory tract infections in children warrants further investigation.",,"['Lin, Feng', 'Guan, Wuxiang', 'Cheng, Fang', 'Yang, Ningmin', 'Pintel, David', 'Qiu, Jianming']",,,,
,PMC,Mutation in murine coronavirus replication protein nsp4 alters assembly of double membrane vesicles,http://dx.doi.org/10.1016/j.virol.2008.01.018,PMC2443636,,,"Coronaviruses are positive-strand RNA viruses that replicate in the cytoplasm of infected cells by generating a membrane-associated replicase complex. The replicase complex assembles on double membrane vesicles (DMVs). Here, we studied the role of a putative replicase anchor, nonstructural protein 4 (nsp4), in the assembly of murine coronavirus DMVs. We used reverse genetics to generate infectious clone viruses (icv) with an alanine substitution at nsp4 glycosylation site N176 or N237, or an asparagine to threonine substitution (nsp4-N258T), which is proposed to confer a temperature sensitive phenotype. We found that nsp4-N237A is lethal and nsp4-N258T generated a virus (designated Alb ts6 icv) that is temperature sensitive for viral replication. Analysis of Alb ts6 icv-infected cells revealed that there was a dramatic reduction in DMVs and that both nsp4 and nsp3 partially localized to mitochondria when cells were incubated at the non-permissive temperature. These results reveal a critical role of nsp4 in directing coronavirus DMV assembly.",,"['Clementz, Mark A.', 'Kanjanahaluethai, Amornrat', 'O’Brien, Timothy E.', 'Baker, Susan C.']",,,,
,PMC,Pro-Inflammatory Functions of Astrocytes Correlate with Viral Clearance and Strain-Dependent Protection from TMEV-Induced Demyelinating Disease,http://dx.doi.org/10.1016/j.virol.2008.01.024,PMC2397444,,,"Intracerebral infection of susceptible strains of mice, e.g. SJL/J, with Theiler’s murine encephalomyelitis virus (TMEV) leads to a persistent CNS infection accompanied by development of a chronic-progressive inflammatory CNS autoimmune demyelinating disease which is clinically and pathologically similar to human multiple sclerosis. In contrast, resistant strains of mice, e.g. C57BL/6 (B6), effectively clear TMEV from the CNS and do not develop demyelinating disease. Although CD8(+) T cells are crucial for viral clearance in B6 mice, SJL mice also mount potent CD8(+) T cell responses against virus, thus the reason for the viral persistence in the CNS in these mice is unclear. Here, we examined innate anti-viral responses of CNS-resident astrocytes as a potential determinant of viral persistence and disease susceptibility. We demonstrate that B6 astrocytes produce significantly higher levels of cytokines, chemokines and adhesion molecules in response to TMEV infection, or stimulation with IFN-γ and TNF-α or poly I:C than SJL mice. In addition, TMEV more effectively induces MHC I molecules on B6 astrocytes than SJL, corresponding with an increased ability to activate TMEV-specific CD8(+) T cells directly ex vivo. These results suggest that enhanced anti-viral responses of B6 astrocytes contribute to the ability of these mice to clear TMEV from the CNS and therefore to their resistance to the development of autoimmune demyelinating disease.",,"['Carpentier, Pamela A.', 'Getts, Meghann Teague', 'Miller, Stephen D.']",,,,
,PMC,In vivo correction of a Menkes disease model using antisense oligonucleotides,http://dx.doi.org/10.1073/pnas.0710865105,PMC2268804,,,"Although the molecular basis of many inherited metabolic diseases has been defined, the availability of effective therapies in such disorders remains problematic. Menkes disease is a fatal neurodegenerative disorder due to loss-of-function mutations in the ATP7A gene encoding a copper-transporting P-type Atpase. To develop therapeutic approaches in affected patients, we have identified a zebrafish model of Menkes disease termed calamity that results from splicing defects in the zebrafish orthologue of the ATP7A gene. Embryonic-recessive lethal mutants have impaired copper homeostasis that results in absent melanin pigmentation, impaired notochord formation, and hindbrain neurodegeneration. In this current study, we have attempted to rescue these striking phenotypic alterations by using a series of antisense morpholino oligonucleotides directed against the splice-site junctions of two mutant calamity alleles. Our findings reveal a robust and complete correction of the copper-deficient defects of calamity in association with the generation of the WT Menkes protein in all rescued mutants. Interestingly, a quantitative analysis of atp7a-specific transcripts suggests that competitive translational regulation may account for the synthesis of WT protein in these embryos. This in vivo correction of Menkes disease through the rescue of aberrant splicing may provide therapeutic options in this fatal disease and illustrates the potential for zebrafish models of human genetic disease in the development of treatments based on the principles of interactions of synthetic oligonucleotide analogues with mRNA.",,"['Madsen, Erik C.', 'Morcos, Paul A.', 'Mendelsohn, Bryce A.', 'Gitlin, Jonathan D.']",,,,
,PMC,A mutant HBs antigen (HBsAg)183–191 epitope elicits specific cytotoxic T lymphocytes in acute hepatitis B patients,http://dx.doi.org/10.1111/j.1365-2249.2007.03570.x,PMC2276963,,,"HBs antigen (HBsAg)183–191 (FLLTRILTI, R187 peptide) is a dominant human leucocyte antigen-A2 (HLA-A2)-restricted epitope associated with hepatitis B virus (HBV) infection in Caucasian populations. However, its prevalence is poorly understood in China, where there is a high incidence of HBV infection. In this report, we sequenced the region of HBsAg derived from 103 Chinese patients. Approximately 16·5% of the patients bore a mutant HBsAg183–191 epitope in which the original arginine (R187) was substituted with a lysine (K187 mutant peptide). Importantly, K187 still bound to HLA-A2 with high affinity, and elicited specific cytotoxic T lymphocyte (CTL) responses in HLA-A2/K(b) transgenic mice. K187-specific CTLs were also generated successfully in acute hepatitis B (AHB) patients, indicating that this mutant epitope is processed and presented effectively. Our findings show that R187-specific CTLs can cross-react with the K187 peptide. These findings reveal that K187 still has the property of an HLA-A2 restricted epitope, and elicits a protective anti-HBV CTL response in humans.",,"['Liu, H-G', 'Fan, Z-P', 'Chen, W-W', 'Yang, H-Y', 'Liu, Q-F', 'Zhang, H', 'Tien, P', 'Wang, F-S']",,,,
,PMC,"A Prospective, Comparative Study of the Immune Response to Inactivated Influenza Vaccine in Pediatric Liver Transplant Recipients and Their Healthy Siblings",http://dx.doi.org/10.1086/527391,PMC2884176,,,"BACKGROUND: Annual influenza vaccination is routinely recommended for pediatric solid organ transplant recipients. However, there are limited data defining the immune response to the inactivated vaccine in this population. METHODS: This prospective study compared the humoral and cell-mediated immune responses to the trivalent subvirion influenza vaccine in pediatric liver transplant recipients with those in their healthy siblings. All subjects received inactivated influenza vaccine. Hemagglutination inhibition and interferon-γ (IFN-γ) enzyme-linked immunosorbent spot assays for New Caledonia and Shanghai strains were performed at baseline, after each vaccine dose, and 3 months after the series. Seroconversion was defined as a 4-fold increase in antibody titers; seroprotection was defined as an antibody titer ≥1:40. An increase in the number of T cells secreting IFN-γ was considered to be a positive enzyme-linked immunosorbent spot response. RESULTS: After 1 dose of vaccine, transplant recipients achieved rates of antibody seroprotection and seroconversion that were similar to those achieved by their healthy siblings. However, for both influenza strains, IFN-γ responses by enzyme-linked immunosorbent spot were significantly attenuated in transplant recipients after 2 doses of vaccine. No cases of influenza or vaccine-related serious adverse events were documented in the study. CONCLUSIONS: The diminished cell-mediated immune response to influenza vaccination that was observed in pediatric liver transplant recipients suggests that the current vaccine strategy may not provide optimal protection. Because of concerns regarding potential emergence of more virulent influenza strains, further studies are warranted to determine if IFN-γ responses are predictive of efficacy and to identify the optimal vaccination strategy to protect populations with a high risk of infection.",,"['Madan, Rebecca Pellett', 'Tan, Maria', 'Fernandez-Sesma, Ana', 'Moran, Thomas M.', 'Emre, Sukru', 'Campbell, Andrew', 'Herold, Betsy C.']",,,,
,PMC,Viral Infection after Renal Transplantation: Surveillance and Management,http://dx.doi.org/10.2215/CJN.02900707,PMC3152274,,,"Viral infections remain a significant cause of morbidity and mortality following renal transplantation. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or post transplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. This review will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens.",,"['Weikert, Blair C.', 'Blumberg, Emily A.']",,,,
,PMC,QRS voltages are transiently increased at the superacute stage of experimental myocarditis,,PMC2435398,,,"BACKGROUND: There are few reports on the precise electrocardiographic characteristics of acute myocarditis. The present study was focused on QRS voltage changes at the superacute stage of murine myocarditis. METHODS: Serial electrocardiograms were recorded during the acute stage of viral myocarditis in mice, and then the cardiac pathology was examined. After recording baseline electrocardiograms, mice (n=235) were inoculated intraperitoneally with the encephalomyocarditis virus, resulting in severe myocarditis. Electrocardiograms were serially recorded until nine days after virus inoculation (superacute stage, days 3 to 6; acute stage, days 7 to 9). Changes in heart rate and QRS voltages were analyzed. RESULTS: Serial electrocardiograms revealed that heart rates began to increase after day 3, and that the sum of the QRS voltages increased on day 3 and then decreased on days 7 to 9. Trivial mononuclear cell infiltrations and interstitial edema were most frequently found in mice at the superacute stage. CONCLUSIONS: Transient increase of the QRS voltages at the superacute stage of myocarditis was demonstrated, which may be due to an increase in ventricular mass caused by interstitial edema at this stage.",,"['Kishimoto, Chiharu', 'Ohmae, Minoru', 'Tomioka, Nobuyoshi']",,,,
,PMC,Comparison of Technicians' Ability to Detect Clinical Signs in Rats Housed in Wire-bottom versus Solid-bottom Cages with Bedding,,PMC2653994,,,"Rodent toxicology studies have historically been performed in wire-bottom cages, but the 1996 Guide for the Care and Use of Laboratory Animals recommends solid-bottom caging with bedding. Some investigators have expressed concern that changing to solid-bottom cages would interfere with technicians' ability to detect clinical signs. To test this hypothesis, rats were housed in both types of caging and given compounds to induce a variety of subtle clinical signs common to toxicology studies including chromodacryorrhea, soft stool, stereotypic behaviors, mild hypoactivity, abnormal postures, and discolored urine. For one comparison, fecal pellets were removed to simulate decreased production of feces. Technicians, blinded from knowing which animals had been treated, observed the rats and recorded the clinical signs they detected. The technicians who administered the treatments verified that clinical signs were present before and after the blinded technicians made their observations. The number of animals observed with clinical signs divided by the number of animals verified with signs was calculated for each compound and compared between the cage types by using the Fisher Exact Test. The only statistically significant difference observed was a diminished ability to detect discolored, dark urine from rats in wire-bottom cages. These results suggest that concerns about technical staff's inability to detect clinical signs in toxicity tests should not prevent investigators from using solid-bottom cages with bedding.",,"['Van Vleet, Terry R', 'Rhodes, James W', 'Waites, C Robbie', 'Schilling, Beth E', 'Nelson, David R', 'Jackson, Todd A']",,,,
,PMC,Effects of an Enrichment Device on Voluntary Alcohol Consumption on Single-Housed Rats,,PMC2653993,,,"We evaluated the effect of an enrichment device (that is, a polyurethane bone) on the voluntary consumption of ethanol-containing gel by single-housed rats. Male Sprague–Dawley rats (n = 5 per group) were exposed for 4 d to each of the following 3 treatments: access to a new synthetic bone and ethanol gel for 1 h daily (treatment 1); a new bone was left in the cage for 24 h, with access to ethanol gel for 1 h daily (treatment 2); and both the bone and ethanol gel remained in the cage for 24 h (treatment 3). Average alcohol consumption over 4 d was 0.86 ± 0.13, 0.99 ± 0.13, and 5.19 ± 0.37 g/kg in the absence of the bone for treatments 1, 2, and 3, respectively, and 1.00 ± 0.13, 0.620 ± 0.07, and 5.55 ± 0.38 g/kg with the bone for treatments 1, 2 and 3, respectively; none of these values differed significantly with regard to presence of the bone. During treatment 1, time spent with the synthetic bone was highest on the first 2 d, which altered the rate of ethanol consumption but not the total amount of ethanol consumed. During treatments 2 and 3, the rate and amount of ethanol consumption were comparable to basal levels. We conclude that adding an enrichment device that rats can chew and manipulate does not alter ethanol gel consumption. If used, environmental enrichment techniques should be evaluated during the research planning stages to avoid unintended alterations in the response to variables of interest.",,"['Ramirez, Harvey E', 'Esperon, Leonardo', 'Peris, Joanna']",,,,
,PMC,HealthMap: Global Infectious Disease Monitoring through Automated Classification and Visualization of Internet Media Reports,http://dx.doi.org/10.1197/jamia.M2544,PMC2274789,,,"OBJECTIVE: Unstructured electronic information sources, such as news reports, are proving to be valuable inputs for public health surveillance. However, staying abreast of current disease outbreaks requires scouring a continually growing number of disparate news sources and alert services, resulting in information overload. Our objective is to address this challenge through the HealthMap.org Web application, an automated system for querying, filtering, integrating and visualizing unstructured reports on disease outbreaks. DESIGN: This report describes the design principles, software architecture and implementation of HealthMap and discusses key challenges and future plans. MEASUREMENTS: We describe the process by which HealthMap collects and integrates outbreak data from a variety of sources, including news media (e.g., Google News), expert-curated accounts (e.g., ProMED Mail), and validated official alerts. Through the use of text processing algorithms, the system classifies alerts by location and disease and then overlays them on an interactive geographic map. We measure the accuracy of the classification algorithms based on the level of human curation necessary to correct misclassifications, and examine geographic coverage. RESULTS: As part of the evaluation of the system, we analyzed 778 reports with HealthMap, representing 87 disease categories and 89 countries. The automated classifier performed with 84% accuracy, demonstrating significant usefulness in managing the large volume of information processed by the system. Accuracy for ProMED alerts is 91% compared to Google News reports at 81%, as ProMED messages follow a more regular structure. CONCLUSION: HealthMap is a useful free and open resource employing text-processing algorithms to identify important disease outbreak information through a user-friendly interface.",,"['Freifeld, Clark C.', 'Mandl, Kenneth D.', 'Reis, Ben Y.', 'Brownstein, John S.']",,,,
,PMC,A Heuristic Indication and Warning Staging Model for Detection and Assessment of Biological Events,http://dx.doi.org/10.1197/jamia.M2558,PMC2274782,,,"OBJECTIVE: This paper presents a model designed to enable rapid detection and assessment of biological threats that may require swift intervention by the international public health community. DESIGN: We utilized Strauss’ grounded theory to develop an expanded model of social disruption due to biological events based on retrospective and prospective case studies. We then applied this model to the temporal domain and propose a heuristic staging model, the Wilson–Collmann Scale for assessing biological event evolution. MEASUREMENTS: We retrospectively and manually examined hard copy archival local media reports in the native vernacular for three biological events associated with substantial social disruption. The model was then tested prospectively through media harvesting based on keywords corresponding to the model parameters. RESULTS: Our heuristic staging model provides valuable information about the features of a biological event that can be used to determine the level of concern warranted, such as whether the pathogen in question is responding to established public health disease control measures, including the use of antimicrobials or vaccines; whether the public health and medical infrastructure of the country involved is adequate to mount the necessary response; whether the country’s officials are providing an appropriate level of information to international public health authorities; and whether the event poses a international threat. The approach is applicable for monitoring open-source (public-domain) media for indications and warnings of such events, and specifically for markers of the social disruption that commonly occur as these events unfold. These indications and warnings can then be used as the basis for staging the biological threat in the same manner that the United States National Weather Service currently uses storm warning models (such as the Saffir-Simpson Hurricane Scale) to detect and assess threatening weather conditions. CONCLUSION: Used as a complement to current epidemiological surveillance methods, our approach could aid global public health officials and national political leaders in responding to biological threats of international public health significance.",,"['Wilson, James M.', 'Polyak, Marat G.', 'Blake, Jane W.', 'Collmann, Jeff']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00139-08,PMC2259005,,,,,,,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00049-08,PMC2258949,,,,,,,,,
,PMC,Blockade of Viral Interleukin 6 Expression of Kaposi's Sarcoma-Associated Herpesvirus,http://dx.doi.org/10.1158/1535-7163.MCT-07-2036,PMC2377409,,,"Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, is associated with several malignant disorders, including Kaposi's sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman's disease. An early lytic gene of KSHV encodes vIL-6, a viral homolog of the pro-inflammatory cytokine and an autocrine/paracrine growth factor human interleukin 6. In this study, we examined the effects of suppressing vIL-6 expression in PEL cells with antisense peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO). PPMO are single-stranded DNA analogues that have a modified backbone and enter cells readily. Treatment of PEL cells with a PPMO designed against vIL-6 mRNA led to a marked reduction in the proportion of vIL-6-positive cells detected by immunofluorescence assay. Analysis by Western blot confirmed a specific reduction in the vIL-6 protein level, and demonstrated that the reduction was dependent on the dose of vIL-6 PPMO. PEL cells treated with the vIL-6 PPMO exhibited reduced levels of cellular growth, IL-6 expression and KSHV DNA, as well as an elevated level of p21 protein. Treatment of PEL cells with a combination of two vIL-6 PPMO compounds targeting different sequences in the vIL-6 mRNA led to an inhibitory effect that was greater than that achieved with either PPMO alone. These results demonstrate that PPMO targeting vIL-6 mRNA can potently reduce vIL-6 protein translation, and indicate that further exploration of these compounds in an animal model for potential clinical application is warranted.",,"['Zhang, Yan-Jin', 'Bonaparte, Rheba S.', 'Patel, Deendayal', 'Stein, David A.', 'Iversen, Patrick L.']",,,,
,PMC,Transfusion-Related Acute Lung Injury (TRALI): Report of 2 Cases and a Review of The Literature,,PMC3096419,,,"Transfusion of allogeneic blood products is given for correction of coagulation deficits and for the improvement in oxygen-carrying capacity or delivery. Blood transfusion has become safer following the advancement in blood testing using state-of-the-art viral assays; however, there continues to exist a variety of noninfectious transfusion risks that still remain and that cannot be entirely eliminated. Research is now directed towards understanding these lesser-known, but serious transfusion-related complications. This purpose of this review is to discuss a serious noninfectious cause of acute lung injury, transfusion-related acute lung injury (TRALI), which occurred in 2 recent cases in the intensive care unit, and to review the current literature of this syndrome.",,"Nossaman, Bobby D.",,,,
,PMC,Health Status and Access to Health Care of Migrant Workers in China,,PMC2239328,,,"OBJECTIVES: We explored living and working conditions, health status, and health-care access in Chinese rural-to-urban migrants and compared them with permanent rural and urban residents. METHODS: A questionnaire was administered to 1,958 urban workers, 1,909 rural workers, and 4,452 migrant workers in Zhejiang Province, Eastern China, in 2004. Blood samples for human immunodeficiency virus (HIV) and syphilis were taken from the migrant and urban workers. RESULTS: Migrants were young, worked very long hours, and their living conditions were very basic. Nineteen percent had some form of health insurance and 26% were entitled to limited sick pay compared with 68% and 66%, respectively, for urban workers. Migrants had the best self-rated health and reported the least acute illness, chronic disease, and disability, after controlling for age and education. There were no HIV infections detected in either the migrant or urban workers. However, 15 urban workers (0.68%, 95% confidence interval [CI] 0.35, 1.02) and 20 migrants (0.48%, 95% CI 0.26, 0.66, p=0.06) tested positive for syphilis. The high cost of health care in the city was a barrier to health-care access in the last year for 15% of the migrants and 8% of the urban workers. Forty-seven percent of the migrants were unwilling to make contributions to health insurance. CONCLUSION: These migrants demonstrated the “healthy migrant effect.” However, poor living conditions and inattention to health may make migrants vulnerable to poor long-term health. Because health insurance schemes will remain limited for the forseeable future, attention should focus on providing affordable health care to both uninsured migrants and the urban poor.",,"['Hesketh, Therese', 'Jun, Ye Xue', 'Lu, Li', 'Mei, Wang Hong']",,,,
,PMC,Management of upper respiratory tract infections in children,,PMC3098742,,,"Upper respiratory tract infection (URTI) occurs commonly in both children and adults and is a major cause of mild morbidity. It has a high cost to society, being responsible for absenteeism from school and work and unnecessary medical care, and is occasionally associated with serious sequelae. URTIs are usually caused by several families of virus; these are the rhinovirus, coronavirus, parainfluenza, respiratory syncytial virus (RSV), adenovirus, human metapneumovirus, influenza, enterovirus and the recently discovered bocavirus. This review will mainly focus on the rhinovirus, where significant advances have been made in understanding the epidemiology, natural history and relationship with other pathogens.",,"['Cotton, MF', 'Innes, S', 'Jaspan, H', 'Madide, A', 'Rabie, H']",,,,
,PMC,Generation interval contraction and epidemic data analysis,http://dx.doi.org/10.1016/j.mbs.2008.02.007,PMC2365921,,,"The generation interval is the time between the infection time of an infected person and the infection time of his or her infector. Probability density functions for generation intervals have been an important input for epidemic models and epidemic data analysis. In this paper, we specify a general stochastic SIR epidemic model and prove that the mean generation interval decreases when susceptible persons are at risk of infectious contact from multiple sources. The intuition behind this is that when a susceptible person has multiple potential infectors, there is a “race” to infect him or her in which only the first infectious contact leads to infection. In an epidemic, the mean generation interval contracts as the prevalence of infection increases. We call this global competition among potential infectors. When there is rapid transmission within clusters of contacts, generation interval contraction can be caused by a high local prevalence of infection even when the global prevalence is low. We call this local competition among potential infectors. Using simulations, we illustrate both types of competition. Finally, we show that hazards of infectious contact can be used instead of generation intervals to estimate the time course of the effective reproductive number in an epidemic. This approach leads naturally to partial likelihoods for epidemic data that are very similar to those that arise in survival analysis, opening a promising avenue of methodological research in infectious disease epidemiology.",,"['Kenah, Eben', 'Lipsitch, Marc', 'Robins, James M.']",,,,
,PMC,RNase-Resistant Virus-Like Particles Containing Long Chimeric RNA Sequences Produced by Two-Plasmid Coexpression System,http://dx.doi.org/10.1128/JCM.02248-07,PMC2395109,,,"RNase-resistant, noninfectious virus-like particles containing exogenous RNA sequences (armored RNA) are good candidates as RNA controls and standards in RNA virus detection. However, the length of RNA packaged in the virus-like particles with high efficiency is usually less than 500 bases. In this study, we describe a method for producing armored L-RNA. Armored L-RNA is a complex of MS2 bacteriophage coat protein and RNA produced in Escherichia coli by the induction of a two-plasmid coexpression system in which the coat protein and maturase are expressed from one plasmid and the target RNA sequence with modified MS2 stem-loop (pac site) is transcribed from another plasmid. A 3V armored L-RNA of 2,248 bases containing six gene fragments—hepatitis C virus, severe acute respiratory syndrome coronavirus (SARS-CoV1, SARS-CoV2, and SARS-CoV3), avian influenza virus matrix gene (M300), and H5N1 avian influenza virus (HA300)—was successfully expressed by the two-plasmid coexpression system and was demonstrated to have all of the characteristics of armored RNA. We evaluated the 3V armored L-RNA as a calibrator for multiple virus assays. We used the WHO International Standard for HCV RNA (NIBSC 96/790) to calibrate the chimeric armored L-RNA, which was diluted by 10-fold serial dilutions to obtain samples containing 10(6) to 10(2) copies. In conclusion, the approach we used for armored L-RNA preparation is practical and could reduce the labor and cost of quality control in multiplex RNA virus assays. Furthermore, we can assign the chimeric armored RNA with an international unit for quantitative detection.",,"['Wei, Yuxiang', 'Yang, Changmei', 'Wei, Baojun', 'Huang, Jie', 'Wang, Lunan', 'Meng, Shuang', 'Zhang, Rui', 'Li, Jinming']",,,,
,PMC,Coronavirus Infection Modulates the Unfolded Protein Response and Mediates Sustained Translational Repression,http://dx.doi.org/10.1128/JVI.00017-08,PMC2293058,,,"During coronavirus replication, viral proteins induce the formation of endoplasmic reticulum (ER)-derived double-membrane vesicles for RNA synthesis, and viral structural proteins assemble virions at the ER-Golgi intermediate compartment. We hypothesized that the association and intense utilization of the ER during viral replication would induce the cellular unfolded protein response (UPR), a signal transduction cascade that acts to modulate translation, membrane biosynthesis, and the levels of ER chaperones. Here, we report that infection by the murine coronavirus mouse hepatitis virus (MHV) triggers the proximal UPR transducers, as revealed by monitoring the IRE1-mediated splicing of XBP-1 mRNA and the cleavage of ATF6α. However, we detected minimal downstream induction of UPR target genes, including ERdj4, ER degradation-enhancing α-mannosidase-like protein, and p58(IPK), or expression of UPR reporter constructs. Translation initiation factor eIF2α is highly phosphorylated during MHV infection, and translation of cellular mRNAs is attenuated. Furthermore, we found that the critical homeostasis regulator GADD34, which recruits protein phosphatase 1 to dephosphorylate eIF2α during the recovery phase of the UPR, is not expressed during MHV infection. These results suggest that MHV modifies the UPR by impeding the induction of UPR-responsive genes, thereby favoring a sustained shutdown of the synthesis of host cell proteins while the translation of viral proteins escalates. The role of this modified response and its potential relevance to viral mechanisms for the evasion of innate defense signaling pathways during coronavirus replication are discussed.",,"['Bechill, John', 'Chen, Zhongbin', 'Brewer, Joseph W.', 'Baker, Susan C.']",,,,
,PMC,"Without Its N-Finger, the Main Protease of Severe Acute Respiratory Syndrome Coronavirus Can Form a Novel Dimer through Its C-Terminal Domain",http://dx.doi.org/10.1128/JVI.02612-07,PMC2293041,,,"The main protease (M(pro)) of severe acute respiratory syndrome coronavirus (SARS-CoV) plays an essential role in the extensive proteolytic processing of the viral polyproteins (pp1a and pp1ab), and it is an important target for anti-SARS drug development. It was found that SARS-CoV M(pro) exists in solution as an equilibrium of both monomeric and dimeric forms, and the dimeric form is the enzymatically active form. However, the mechanism of SARS-CoV M(pro) dimerization, especially the roles of its N-terminal seven residues (N-finger) and its unique C-terminal domain in the dimerization, remain unclear. Here we report that the SARS-CoV M(pro) C-terminal domain alone (residues 187 to 306; M(pro)-C) is produced in Escherichia coli in both monomeric and dimeric forms, and no exchange could be observed between them at room temperature. The M(pro)-C dimer has a novel dimerization interface. Meanwhile, the N-finger deletion mutant of SARS-CoV M(pro) also exists as both a stable monomer and a stable dimer, and the dimer is formed through the same C-terminal-domain interaction as that in the M(pro)-C dimer. However, no C-terminal domain-mediated dimerization form can be detected for wild-type SARS-CoV M(pro). Our study results help to clarify previously published controversial claims about the role of the N-finger in SARS-CoV M(pro) dimerization. Apparently, without the N-finger, SARS-CoV M(pro) can no longer retain the active dimer structure; instead, it can form a new type of dimer which is inactive. Therefore, the N-finger of SARS-CoV M(pro) is not only critical for its dimerization but also essential for the enzyme to form the enzymatically active dimer.",,"['Zhong, Nan', 'Zhang, Shengnan', 'Zou, Peng', 'Chen, Jiaxuan', 'Kang, Xue', 'Li, Zhe', 'Liang, Chao', 'Jin, Changwen', 'Xia, Bin']",,,,
,PMC,"Severe Acute Respiratory Syndrome Coronavirus nsp1 Suppresses Host Gene Expression, Including That of Type I Interferon, in Infected Cells",http://dx.doi.org/10.1128/JVI.02472-07,PMC2293030,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 protein has unique biological functions that have not been described in the viral proteins of any RNA viruses; expressed SARS-CoV nsp1 protein has been found to suppress host gene expression by promoting host mRNA degradation and inhibiting translation. We generated an nsp1 mutant (nsp1-mt) that neither promoted host mRNA degradation nor suppressed host protein synthesis in expressing cells. Both a SARS-CoV mutant virus, encoding the nsp1-mt protein (SARS-CoV-mt), and a wild-type virus (SARS-CoV-WT) replicated efficiently and exhibited similar one-step growth kinetics in susceptible cells. Both viruses accumulated similar amounts of virus-specific mRNAs and nsp1 protein in infected cells, whereas the amounts of endogenous host mRNAs were clearly higher in SARS-CoV-mt-infected cells than in SARS-CoV-WT-infected cells, in both the presence and absence of actinomycin D. Further, SARS-CoV-WT replication strongly inhibited host protein synthesis, whereas host protein synthesis inhibition in SARS-CoV-mt-infected cells was not as efficient as in SARS-CoV-WT-infected cells. These data revealed that nsp1 indeed promoted host mRNA degradation and contributed to host protein translation inhibition in infected cells. Notably, SARS-CoV-mt infection, but not SARS-CoV-WT infection, induced high levels of beta interferon (IFN) mRNA accumulation and high titers of type I IFN production. These data demonstrated that SARS-CoV nsp1 suppressed host innate immune functions, including type I IFN expression, in infected cells and suggested that SARS-CoV nsp1 most probably plays a critical role in SARS-CoV virulence.",,"['Narayanan, Krishna', 'Huang, Cheng', 'Lokugamage, Kumari', 'Kamitani, Wataru', 'Ikegami, Tetsuro', 'Tseng, Chien-Te K.', 'Makino, Shinji']",,,,
,PMC,Mechanism for Controlling the Dimer-Monomer Switch and Coupling Dimerization to Catalysis of the Severe Acute Respiratory Syndrome Coronavirus 3C-Like Protease,http://dx.doi.org/10.1128/JVI.02680-07,PMC2293028,,,"Unlike 3C protease, the severe acute respiratory syndrome coronavirus (SARS-CoV) 3C-like protease (3CLpro) is only enzymatically active as a homodimer and its catalysis is under extensive regulation by the unique extra domain. Despite intense studies, two puzzles still remain: (i) how the dimer-monomer switch is controlled and (ii) why dimerization is absolutely required for catalysis. Here we report the monomeric crystal structure of the SARS-CoV 3CLpro mutant R298A at a resolution of 1.75 Å. Detailed analysis reveals that Arg298 serves as a key component for maintaining dimerization, and consequently, its mutation will trigger a cooperative switch from a dimer to a monomer. The monomeric enzyme is irreversibly inactivated because its catalytic machinery is frozen in the collapsed state, characteristic of the formation of a short 3(10)-helix from an active-site loop. Remarkably, dimerization appears to be coupled to catalysis in 3CLpro through the use of overlapped residues for two networks, one for dimerization and another for the catalysis.",,"['Shi, Jiahai', 'Sivaraman, J.', 'Song, Jianxing']",,,,
,PMC,Formation of the Arterivirus Replication/Transcription Complex: a Key Role for Nonstructural Protein 3 in the Remodeling of Intracellular Membranes,http://dx.doi.org/10.1128/JVI.02756-07,PMC2293027,,,"The replication/transcription complex of the arterivirus equine arteritis virus (EAV) is associated with paired membranes and/or double-membrane vesicles (DMVs) that are thought to originate from the endoplasmic reticulum. Previously, coexpression of two putative transmembrane nonstructural proteins (nsp2 and nsp3) was found to suffice to induce these remarkable membrane structures, which are typical of arterivirus infection. Here, site-directed mutagenesis was used to investigate the role of nsp3 in more detail. Liberation of the hydrophobic N terminus of nsp3, which is normally achieved by cleavage of the nsp2/3 junction by the nsp2 protease, was nonessential for the formation of DMVs. However, the substitution of each of a cluster of four conserved cysteine residues, residing in a predicted luminal loop of nsp3, completely blocked DMV formation. Some of these mutant nsp3 proteins were also found to be highly cytotoxic, in particular, exerting a dramatic effect on the endoplasmic reticulum. The functionality of an engineered N glycosylation site in the cysteine-containing loop confirmed both its presence in the lumen and the transmembrane nature of nsp3. This mutant displayed an interesting intermediate phenotype in terms of DMV formation, with paired and curved membranes being formed, but DMV formation apparently being impaired. The effect of nsp3 mutations on replicase polyprotein processing was investigated, and several mutations were found to influence processing of the region downstream of nsp3 by the nsp4 main protease. When tested in an EAV reverse genetics system, none of the nsp3 mutations was tolerated, again underlining the crucial role of the protein in the arterivirus life cycle.",,"['Posthuma, Clara C.', 'Pedersen, Ketil W.', 'Lu, Zhengchun', 'Joosten, Ruth G.', 'Roos, Norbert', 'Zevenhoven-Dobbe, Jessika C.', 'Snijder, Eric J.']",,,,
,PMC,Noninvasive positive-pressure ventilation,http://dx.doi.org/10.1503/cmaj.1070174,PMC2244681,,,,,"['Puro, Vincenzo', 'Fusco, Francesco Maria', 'Pittalis, Silvia', 'Lanini, Simone', 'Ippolito, Giuseppe']",,,,
,PMC,Constructing the effect of alternative intervention strategies on historic epidemics,http://dx.doi.org/10.1098/rsif.2008.0030,PMC3227033,,,"Data from historical epidemics provide a vital and sometimes under-used resource from which to devise strategies for future control of disease. Previous methods for retrospective analysis of epidemics, in which alternative interventions are compared, do not make full use of the information; by using only partial information on the historical trajectory, augmentation of control may lead to predictions of a paradoxical increase in disease. Here we introduce a novel statistical approach that takes full account of the available information in constructing the effect of alternative intervention strategies in historic epidemics. The key to the method lies in identifying a suitable mapping between the historic and notional outbreaks, under alternative control strategies. We do this by using the Sellke construction as a latent process linking epidemics. We illustrate the application of the method with two examples. First, using temporal data for the common human cold, we show the improvement under the new method in the precision of predictions for different control strategies. Second, we show the generality of the method for retrospective analysis of epidemics by applying it to a spatially extended arboreal epidemic in which we demonstrate the relative effectiveness of host culling strategies that differ in frequency and spatial extent. Some of the inferential and philosophical issues that arise are discussed along with the scope of potential application of the new method.",,"['Cook, A.R', 'Gibson, G.J', 'Gottwald, T.R', 'Gilligan, C.A']",,,,
,PMC,Renal magnification by EGF,http://dx.doi.org/10.1093/ndt/gfm952,PMC4048937,,,"A paper recently published by Groenestege and colleagues [8] used positional cloning to determine the cause of a rare inherited magnesium-wasting syndrome, autosomal recessive renal hypomagnesemia. The results showed that certain mutations in the epidermal growth factor (EGF) gene cause this disease. This suggests, perhaps surprisingly, that EGF and its receptor comprise a previously unrecognized signaling pathway in the human kidney that participates importantly in magnesium homeostasis. The EGF gene is highly expressed along the distal convoluted tubule (DCT), an important site for regulating urinary magnesium excretion. The product of the gene is a large membrane-bound molecule, expressed at both the apical and basolateral surfaces. A portion of the extracellular domain can be cleaved to form the 53-amino-acid hormone, EGF; it is believed that cleavage occurs preferentially at the basolateral surface, leading to increased apparent EGF abundance at the apical membrane. In the DCT, EGF binds to receptors at the basolateral surface, making basolateral EGF expression a necessary prerequisite for signaling. The gene defect that causes autosomal recessive renal hypomagnesemia appears to disrupt trafficking of pro-EGF to the basolateral membrane, thereby impeding its signaling capability. The results also showed that EGF stimulates magnesium transport by TRPM6 (transient receptor potential cation channel, subfamily M, member 6), a channel that is expressed at the apical membrane of DCT cells and appears to be a primary path for apical magnesium entry. Interestingly, the investigators also corroborated previous reports that cancer patients treated with an antagonist of the EGF receptor, cetuximab, develop renal magnesium wasting and hypomagnesemia, emphasizing the significance of EGF in maintaining magnesium balance in humans.",,"Ellison, David H.",,,,
,PMC,Global trends in emerging infectious diseases,http://dx.doi.org/10.1038/nature06536,PMC5960580,,,"Emerging infectious diseases (EIDs) are a significant burden on global economies and public health(1–3). Their emergence is thought to be driven largely by socio-economic, environmental and ecological factors(1–9), but no comparative study has explicitly analysed these linkages to understand global temporal and spatial patterns of EIDs. Here we analyse a database of 335 EID ‘events’ (origins of EIDs) between 1940 and 2004, and demonstrate non-random global patterns. EID events have risen significantly over time after controlling for reporting bias, with their peak incidence (in the 1980s) concomitant with the HIV pandemic. EID events are dominated by zoonoses (60.3% of EIDs): the majority of these (71.8%) originate in wildlife (for example, severe acute respiratory virus, Ebola virus), and are increasing significantly over time. We find that 54.3% of EID events are caused by bacteria or rickettsia, reflecting a large number of drug-resistant microbes in our database. Our results confirm that EID origins are significantly correlated with socio-economic, environmental and ecological factors, and provide a basis for identifying regions where new EIDs are most likely to originate (emerging disease ‘hotspots’). They also reveal a substantial risk of wildlife zoonotic and vector-borne EIDs originating at lower latitudes where reporting effort is low. We conclude that global resources to counter disease emergence are poorly allocated, with the majority of the scientific and surveillance effort focused on countries from where the next important EID is least likely to originate.",,"['Jones, Kate E.', 'Patel, Nikkita G.', 'Levy, Marc A.', 'Storeygard, Adam', 'Balk, Deborah', 'Gittleman, John L.', 'Daszak, Peter']",,,,
,PMC,Cytokine Responses in Porcine Respiratory Coronavirus-Infected Pigs Treated with Corticosteroids as a Model for Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1128/JVI.02190-07,PMC2293053,,,"The effectiveness and potential immunosuppressive effects of anti-inflammatory glucocorticoids in the lungs of severe acute respiratory syndrome (SARS) patients are undefined. We treated porcine respiratory coronavirus (PRCV)-infected conventional pigs with the corticosteroid dexamethasone (DEX) as a model for SARS. Innate and Th1 cytokines in bronchoalveolar lavage (BAL) and serum were elevated in PRCV-infected pigs compared to controls, but were decreased after DEX treatment in the PRCV-infected, DEX-treated (PRCV/DEX) pigs. Although decreased in BAL, Th2 cytokine levels were higher in serum after DEX treatment. Levels of the proinflammatory cytokine interleukin-6 in BAL and serum were decreased in PRCV/DEX pigs early but increased later compared to those in phosphate-buffered saline-treated, PRCV-infected pigs, corresponding to a similar trend for lung lesions. PRCV infection increased T-cell frequencies in BAL, but DEX treatment of PRCV-infected pigs reduced frequencies of T cells; interestingly B and SWC3a(+) (monocytes/macrophages/granulocytes) cell frequencies were increased. DEX reduced numbers of PRCV-stimulated Th1 gamma interferon-secreting cells in spleen, tracheobroncheolar lymph nodes, and blood. Our findings suggest that future glucocorticoid treatment of SARS patients should be reconsidered in the context of potential local immunosuppression of immune responses in lung and systemic Th1 cytokine-biased suppression.",,"['Zhang, Xinsheng', 'Alekseev, Konstantin', 'Jung, Kwonil', 'Vlasova, Anastasia', 'Hadya, Nagesh', 'Saif, Linda J.']",,,,
,PMC,Identification of a GP64 Subdomain Involved in Receptor Binding by Budded Virions of the Baculovirus Autographica californica Multicapsid Nucleopolyhedrovirus,http://dx.doi.org/10.1128/JVI.02490-07,PMC2293031,,,"Enveloped virus entry into host cells is typically initiated by an interaction between a viral envelope glycoprotein and a host cell receptor. For budded virions of the baculovirus Autographa californica multicapsid nucleopolyhedrovirus, the envelope glycoprotein GP64 is involved in host cell receptor binding, and GP64 is sufficient to mediate low-pH-triggered membrane fusion. To better define the role of GP64 in receptor binding, we generated and characterized a panel of antisera against subdomains of GP64. Eight subdomain-specific antisera were generated, and their reactivities with GP64 proteins and neutralization of virus infectivity and binding were examined. Antibodies directed against the N-terminal region of GP64 (amino acids 21 to 159) showed strong neutralization of infectivity and effectively inhibited binding of (35)S-labeled budded virions to Sf9 cells. In addition, we generated virions displaying truncated GP64 constructs. A construct displaying the N-terminal 274 amino acids (residues 21 to 294) of the ectodomain was sufficient to mediate virion binding. Additional studies of antisera directed against small subdomains revealed that an antiserum against a 40-amino-acid region (residues 121 to 160) neutralized virus infectivity. Site-directed mutagenesis was subsequently used for functional analysis of that region. Recombinant viruses expressing GP64 proteins with single amino acid substitutions within amino acids 120 to 124 and 142 to 148 replicated to high titers, suggesting that those amino acids were not critical for receptor binding or other important GP64 functions. In contrast, GP64 proteins with single amino acid substitutions of residues 153 and 156 were unable to substitute for wild-type GP64 and did not rescue a gp64 knockout virus. Further analysis showed that these substitutions substantially reduced binding of recombinant virus to Sf9 cells. Thus, the amino acid region from positions 21 to 159 was identified as a putative receptor binding domain, and amino acids 153 and 156 appear to be important for receptor binding.",,"['Zhou, Jian', 'Blissard, Gary W.']",,,,
,PMC,"XBP-1, a Novel Human T-Lymphotropic Virus Type 1 (HTLV-1) Tax Binding Protein, Activates HTLV-1 Basal and Tax-Activated Transcription",http://dx.doi.org/10.1128/JVI.02054-07,PMC2293026,,,"X-box binding protein 1 (XBP-1), a basic leucine zipper transcription factor, plays a key role in the cellular unfolded protein response (UPR). There are two XBP-1 isoforms in cells, spliced XBP-1S and unspliced XBP-1U. XBP-1U has been shown to bind to the 21-bp Tax-responsive element of the human T-lymphotropic virus type 1 (HTLV-1) long terminal repeat (LTR) in vitro and transactivate HTLV-1 transcription. Here we identify XBP-1S as a transcription activator of HTLV-1. Compared to XBP-1U, XBP-1S demonstrates stronger activating effects on both basal and Tax-activated HTLV-1 transcription in cells. Our results show that both XBP-1S and XBP-1U interact with Tax and bind to the HTLV-1 LTR in vivo. In addition, elevated mRNA levels of the gene for XBP-1 and several UPR genes were detected in the HTLV-1-infected C10/MJ and MT2 T-cell lines, suggesting that HTLV-1 infection may trigger the UPR in host cells. We also identify Tax as a positive regulator of the expression of the gene for XBP-1. Activation of the UPR by tunicamycin showed no effect on the HTLV-1 LTR, suggesting that HTLV-1 transcription is specifically regulated by XBP-1. Collectively, our study demonstrates a novel host-virus interaction between a cellular factor XBP-1 and transcriptional regulation of HTLV-1.",,"['Ku, Sebastian C. Y.', 'Lee, Jialing', 'Lau, Joanne', 'Gurumurthy, Meera', 'Ng, Raymond', 'Lwa, Siew Hui', 'Lee, Joseph', 'Klase, Zachary', 'Kashanchi, Fatah', 'Chao, Sheng-Hao']",,,,
,PMC,Enhancement of Antibody Responses to Bacillus anthracis Protective Antigen Domain IV by Use of Calreticulin as a Chimeric Molecular Adjuvant,http://dx.doi.org/10.1128/IAI.01722-07,PMC2346671,,,"The generation of protective humoral immune responses against the receptor-binding domain (domain IV) of protective antigen [PA(dIV)] of Bacillus anthracis represents a plausible approach against anthrax toxin. In the current study, we have developed a naked DNA vaccine encoding calreticulin (CRT) linked to PA(dIV) of Bacillus anthracis [CRT/PA(dIV)]. We transfected a human embryonic kidney cell line (HEK 293) with CRT/PA(dIV) DNA and performed Western blotting and confocal microscopy analysis. We found that linkage of CRT to PA(dIV) targets PA(dIV) to the endoplasmic reticulum, resulting in secretion of the chimeric CRT/PA(dIV) protein. We then evaluated the ability of CRT/PA(dIV) DNA to generate PA(dIV)-specific antibody responses and protective immunity against lethal anthrax toxin (PA plus lethal factor) challenge. We found that mice immunized with CRT/PA(dIV) DNA were capable of rapidly inducing significantly higher PA(dIV)-specific antibody responses than mice immunized with PA(dIV) DNA alone. Furthermore, we observed that this enhanced antibody response generated by CRT/PA(dIV) DNA was CD4 dependent, since CD4 knockout mice demonstrated a significant reduction in antibody responses. In addition, analysis of the titers and avidity maturation of the induced PA-specific antibodies revealed that vaccination with CRT/PA(dIV) DNA vaccine accelerated the avidity maturation of antibodies to PA(dIV) compared to vaccination with PA(dIV) DNA. Importantly, the enhanced antibody responses correlated to protective immunity against lethal anthrax toxin challenge. Thus, DNA vaccines encoding CRT linked to PA(dIV) may dramatically enhance PA-specific protective antibody responses. Our results have significant clinical applications for biodefense against anthrax toxin.",,"['Park, Yong Sung', 'Lee, Jin Hyup', 'Hung, Chien-Fu', 'Wu, T.-C.', 'Kim, Tae Woo']",,,,
,PMC,A virocidal amphipathic α-helical peptide that inhibits hepatitis C virus infection in vitro,http://dx.doi.org/10.1073/pnas.0712380105,PMC2268589,,,"An amphipathic α-helical peptide (C5A) derived from the membrane anchor domain of the hepatitis C virus (HCV) NS5A protein is virocidal for HCV at submicromolar concentrations in vitro. C5A prevents de novo HCV infection and suppresses ongoing infection by inactivating both extra- and intracellular infectious particles, and it is nontoxic in vitro and in vivo at doses at least 100-fold higher than required for antiviral activity. Mutational analysis indicates that C5A's amphipathic α-helical structure is necessary but not sufficient for its virocidal activity, which depends on its amino acid composition but not its primary sequence or chirality. In addition to HCV, C5A inhibits infection by selected flaviviruses, paramyxoviruses, and HIV. These results suggest a model in which C5A destabilizes viral membranes based on their lipid composition, offering a unique therapeutic approach to HCV and other viral infections.",,"['Cheng, Guofeng', 'Montero, Ana', 'Gastaminza, Pablo', 'Whitten-Bauer, Christina', 'Wieland, Stefan F.', 'Isogawa, Masanori', 'Fredericksen, Brenda', 'Selvarajah, Suganya', 'Gallay, Philippe A.', 'Ghadiri, M. Reza', 'Chisari, Francis V.']",,,,
,PMC,Genetic Strategy to Prevent Influenza Virus Infections in Animals,http://dx.doi.org/10.1086/524987,PMC2694447,,,"The natural reservoirs of influenza viruses are aquatic birds. After adaptation, avian viruses can acquire the ability to infect humans and cause severe disease. Because domestic poultry serves as a key link between the natural reservoir of influenza viruses and epidemics and pandemics in human populations, an effective measure to control influenza would be to eliminate or reduce influenza virus infection in domestic poultry. The development and distribution of influenza-resistant poultry represents a proactive strategy for controlling the origin of influenza epidemics and pandemics in both poultry and human populations. Recent developments in RNA interference and transgenesis in birds should facilitate the development of influenza-resistant poultry.",,"['Chen, Jianzhu', 'Chen, Steve C.-Y.', 'Stern, Patrick', 'Scott, Benjamin B.', 'Lois, Carlos']",,,,
,PMC,Zinc Mesoporphyrin Induces Rapid and Marked Degradation of the Transcription Factor Bach1 and Up-regulates HO-1,http://dx.doi.org/10.1016/j.bbagrm.2008.01.006,PMC2346609,,,"Heme oxygenase 1 (HO-1) is the first and rate-controlling enzyme in heme degradation. Bach1 is a mammalian transcriptional repressor of HO-1. To understand how zinc mesoporphyrin (ZnMP) induces the expression of HO-1, we investigated the effects of ZnMP on Bach1 mRNA and protein levels in human hepatoma Huh-7 cells by quantitative RT-PCR and Western blots. We found that ZnMP markedly up-regulated HO-1 mRNA and protein levels, and rapidly and significantly decreased Bach1 protein levels by increasing degradation of Bach1 protein [half life (t(1/2)) from 19 h to 45 min], whereas ZnMP did not influence Bach1 mRNA levels. The proteasome inhibitors, epoxomicin and MG132, significantly inhibited degradation of Bach1 by ZnMP in a dose-dependent fashion, indicating the degradation of Bach1 by ZnMP is proteasome dependent. Purified Bach1 C-terminal fragment bound heme, but there was no evidence for binding of ZnMP to the heme-binding region of Bach1. In conclusion, ZnMP produces profound post-transcriptional down-regulation of Bach1 protein levels and transcriptional up-regulation of HO-1. Our results indicate that ZnMP up-regulates HO-1 gene expression by markedly increasing Bach1 protein degradation in a proteasome-dependent manner.",,"['Hou, Weihong', 'Shan, Ying', 'Zheng, Jianyu', 'Lambrecht, Richard W.', 'Donohue, Susan E.', 'Bonkovsky, Herbert L.']",,,,
,PMC,Clinical Evaluation of NucliSENS Magnetic Extraction and NucliSENS Analyte-Specific Reagents for Real-Time Detection of Human Metapneumovirus in Pediatric Respiratory Specimens,http://dx.doi.org/10.1128/JCM.01567-07,PMC2292934,,,"In this study, we evaluated the NucliSENS miniMAG (MM) and easyMAG (EM) nucleic acid extraction platforms (bioMérieux, Durham, NC) in combination with the NucliSENS EasyQ basic kit and analyte-specific reagents (ASRs) (bioMérieux) for the detection of human metapneumovirus (hMPV) in respiratory samples. Total nucleic acids from pediatric clinical samples (n = 653) and an hMPV-specific inhibition control (h-IC) were coextracted using the MM and/or the EM. Nucleic acid sequence-based amplification and real-time molecular beacon detection of hMPV were performed using a NucliSENS EasyQ analyzer (bioMérieux). Positive results were confirmed using an in-house-validated reverse transcriptase PCR ASR-based assay. The inclusion of the h-IC monitored the entire process, including the efficiency of nucleic acid extraction, amplification, and detection. The percentages of samples with inhibited amplification of the h-IC after initial NA extraction by EM and MM were 1.88% and 3.17%, respectively. After reprocessing of a new aliquot, the final h-IC inhibition rates were 0% (EM) and 1.06% (MM). The limit of detection of the assay was between 2 (EM extraction) and 10 (MM extraction) RNA copies/reaction, and specificity was 100% when testing viral respiratory isolates and clinical samples. hMPV was detected in 5.6% of pediatric samples tested and was also detected in three coinfections with respiratory syncytial virus (RSV). hMPV was the second most frequently detected respiratory virus in children of 0 to 2 years of age, after RSV. In summary, NucliSENS extraction and ASRs provided a sensitive and specific method for the detection of hMPV in respiratory samples.",,"['Ginocchio, Christine C.', 'Manji, Ryhana', 'Lotlikar, Madhavi', 'Zhang, Fan']",,,,
,PMC,Smallpox Virus Resequencing GeneChips Can Also Rapidly Ascertain Species Status for Some Zoonotic Non-Variola Orthopoxviruses,http://dx.doi.org/10.1128/JCM.00158-08,PMC2292925,,,"We recently developed a set of seven resequencing GeneChips for the rapid sequencing of Variola virus strains in the WHO Repository of the Centers for Disease Control and Prevention. In this study, we attempted to hybridize these GeneChips with some known non-Variola orthopoxvirus isolates, including monkeypox, cowpox, and vaccinia viruses, for rapid detection.",,"['Sulaiman, Irshad M.', 'Sammons, Scott A.', 'Wohlhueter, Robert M.']",,,,
,PMC,Identification of a Coronavirus Transcription Enhancer,http://dx.doi.org/10.1128/JVI.02622-07,PMC2292980,,,"Coronavirus (CoV) transcription includes a discontinuous mechanism during the synthesis of sub-genome-length minus-strand RNAs leading to a collection of mRNAs in which the 5′ terminal leader sequence is fused to contiguous genome sequences. It has been previously shown that transcription-regulating sequences (TRSs) preceding each gene regulate transcription. Base pairing between the leader TRS (TRS-L) and the complement of the body TRS (cTRS-B) in the nascent RNA is a determinant factor during CoV transcription. In fact, in transmissible gastroenteritis CoV, a good correlation has been observed between subgenomic mRNA (sg mRNA) levels and the free energy (ΔG) of TRS-L and cTRS-B duplex formation. The only exception was sg mRNA N, the most abundant sg mRNA during viral infection in spite of its minimum ΔG associated with duplex formation. We postulated that additional factors should regulate transcription of sg mRNA N. In this report, we have described a novel transcription regulation mechanism operating in CoV by which a 9-nucleotide (nt) sequence located 449 nt upstream of the N gene TRS core sequence (CS-N) interacts with a complementary sequence just upstream of CS-N, specifically increasing the accumulation of sg mRNA N. Alteration of this complementarity in mutant replicon genomes showed a correlation between the predicted stability of the base pairing between 9-nt sequences and the accumulation of sg mRNA N. This interaction is exclusively conserved in group 1a CoVs, the only CoV subgroup in which the N gene is not the most 3′ gene in the viral genome. This is the first time that a long-distance RNA-RNA interaction regulating transcriptional activity specifically enhancing the transcription of one gene has been described to occur in CoVs.",,"['Moreno, José L.', 'Zúñiga, Sonia', 'Enjuanes, Luis', 'Sola, Isabel']",,,,
,PMC,IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia,http://dx.doi.org/10.1038/nm1710,PMC2901867,,,"Emerging evidence supports the concept that T helper type 17 (T(H)17) cells, in addition to mediating autoimmunity, have key roles in mucosal immunity against extracellular pathogens. Interleukin-22 (IL-22) and IL-17A are both effector cytokines produced by the T(H)17 lineage, and both were crucial for maintaining local control of the Gram-negative pulmonary pathogen, Klebsiella pneumoniae. Although both cytokines regulated CXC chemokines and granulocyte colony–stimulating factor production in the lung, only IL-22 increased lung epithelial cell proliferation and increased transepithelial resistance to injury. These data support the concept that the T(H)17 cell lineage and its effector molecules have evolved to effect host defense against extracellular pathogens at mucosal sites.",,"['Aujla, Shean J', 'Chan, Yvonne R', 'Zheng, Mingquan', 'Fei, Mingjian', 'Askew, David J', 'Pociask, Derek A', 'Reinhart, Todd A', 'McAllister, Florencia', 'Edeal, Jennifer', 'Gaus, Kristi', 'Husain, Shahid', 'Kreindler, James L', 'Dubin, Patricia J', 'Pilewski, Joseph M', 'Myerburg, Mike M', 'Mason, Carol A', 'Iwakura, Yoichiro', 'Kolls, Jay K']",,,,
,PMC,Autophagy and antiviral immunity,http://dx.doi.org/10.1016/j.coi.2008.01.001,PMC2271118,,,"Autophagy is an ancient pathway designed to maintain cellular homeostasis by degrading long-lived proteins and organelles in the cytosol. Recent studies demonstrate that autophagy is utilized by the cells of the innate and adaptive immune systems to combat viral infections. Autophagy plays a key role in recognizing signatures of viral infection, and represents a critical effector mechanism to restrict viral replication. On the other hand, autophagosomes have been exploited by certain viruses as a niche for viral replication. Furthermore, autophagy can be used to deliver endogenous viral antigens to the MHC class II loading compartment, allowing activation of CD4 T cells. In this review, we describe recent advances in the field of autophagy as it relates to innate and adaptive antiviral immune responses.",,"['Lee, Heung Kyu', 'Iwasaki, Akiko']",,,,
,PMC,Variable responses of formyl peptide receptor haplotypes toward bacterial peptides,http://dx.doi.org/10.1007/s00251-008-0277-3,PMC2435592,,,"The chemoattractant neutrophil formyl peptide receptor (FPR) binds bacterial and mitochondrial N-formylated peptides, which allows the neutrophils to find the bacterial source and/or site of tissue damage. Certain inflammatory disorders may be due in part to an impaired innate immune system that does not respond to acute bacterial damage in a timely fashion. Since the human FPR is encoded by a large number of different haplotypes arising from ten single nucleotide polymorphisms, we examined the possibility that some of these haplotypes are functionally distinct. We analyzed the response of three common FPR haplotypes to peptides from Escherichia coli, Mycobacterium avium ssp. paratuberculosis and human mitochondria. All three haplotypes responded similarly to the E. coli and mitochondrial peptides, whereas one required a higher concentration of the M. avium peptide fMFEDAVAWF for receptor downregulation, receptor signaling and chemotaxis. This raises the possibility of additional bacterial species differences in functional responses among FPR variants, and establishes a precedent with potentially important implications for our innate immune response against bacterial infections. We also investigated whether certain FPR haplotypes are associated with rheumatoid arthritis (RA) by sequencing FPR1 from 148 Caucasian individuals. The results suggested that FPR haplotypes do not significantly contribute toward RA.",,"['Gripentrog, Jeannie M.', 'Mills, John S.', 'Saari, George J.', 'Miettinen, Heini M.']",,,,
,PMC,RespiFinder: a New Multiparameter Test To Differentially Identify Fifteen Respiratory Viruses,http://dx.doi.org/10.1128/JCM.02294-07,PMC2292964,,,"Broad-spectrum analysis for pathogens in patients with respiratory tract infections is becoming more relevant as the number of potential infectious agents is still increasing. Here we describe the new multiparameter RespiFinder assay, which is based on the multiplex ligation-dependent probe amplification (MLPA) technology. This assay detects 15 respiratory viruses in one reaction. The MLPA reaction is preceded by a preamplification step which ensures the detection of both RNA and DNA viruses with the same specificity and sensitivity as individual monoplex real-time reverse transcription-PCRs. The RespiFinder assay was validated with 144 clinical samples, and the results of the assay were compared to those of cell culture and a respiratory syncytial virus (RSV)-specific immunochromatography assay (ICA). Compared to the cell culture results, the RespiFinder assay showed specificities and sensitivities of 98.2% and 100%, respectively, for adenovirus; 96.4% and 100%, respectively, for human metapneumovirus; 98.2% and 100%, respectively, for influenza A virus (InfA); 99.1% and 100%, respectively, for parainfluenza virus type 1 (PIV-1); 99.1% and 80%, respectively, for PIV-3; 90.1% and 100%, respectively, for rhinovirus; and 94.6% and 100%, respectively, for RSV. Compared to the results of the RSV-specific ICA, the RespiFinder assay gave a specificity and a sensitivity of 82.4% and 80%, respectively. PIV-2, PIV-4, influenza B virus, InfA H5N1, and coronavirus 229E were not detected in the clinical specimens tested. The use of the RespiFinder assay resulted in an increase in the diagnostic yield compared to that obtained by cell culture (diagnostic yields, 60% and 35.5%, respectively). In conclusion, the RespiFinder assay provides a user-friendly and high-throughput tool for the simultaneous detection of 15 respiratory viruses with excellent overall performance statistics.",,"['Reijans, Martin', 'Dingemans, Gijs', 'Klaassen, Corné H.', 'Meis, Jacques F.', 'Keijdener, Judith', 'Mulders, Brit', 'Eadie, Kimberly', 'van Leeuwen, Willem', 'van Belkum, Alex', 'Horrevorts, Alphons M.', 'Simons, Guus']",,,,
,PMC,Single-Dose Protection against Plasmodium berghei by a Simian Adenovirus Vector Using a Human Cytomegalovirus Promoter Containing Intron A,http://dx.doi.org/10.1128/JVI.02568-07,PMC2293012,,,"Human adenovirus serotype 5 (AdH5) vector vaccines elicit strong immune responses to the encoded antigen and have been used in various disease models. We designed AdH5 vectors expressing antigen under the control of a human cytomegalovirus (HCMV) immediate-early promoter containing its intron A sequence. The transcriptional levels of antigen and immune responses to antigen for vectors with the HCMV promoter with the intron A sequence (LP) were greater than those for AdH5 vectors using the HCMV promoter sequence without intron A (SP). We compared an E1E3-deleted AdH5 adenoviral vector, which affords more space for insertion of foreign sequences, and showed it to be as immunogenic as an E1-deleted AdH5 vector. Neutralizing antibodies to AdH5 limit the efficacy of vaccines based on the AdH5 serotype, and simian adenoviral vectors offer an attractive option to overcome this problem. We constructed E1E3-deleted human and simian adenoviral vectors encoding the pre-erythrocytic-stage malarial antigen Plasmodium berghei circumsporozoite protein. We compared the immunogenicity and efficacy of AdC6, a recombinant simian adenovirus serotype 6 vector, in a murine malaria model to those of AdH5 and the poxviral vectors MVA and FP9. AdC6 induced sterile protection from a single dose in 90% of mice, in contrast to AdH5 (25%) and poxviral vectors MVA and FP9 (0%). Adenoviral vectors maintained potent CD8(+) T-cell responses for a longer period after immunization than did poxviral vectors and mainly induced an effector memory phenotype of cells. Significantly, AdC6 was able to maintain protection in the presence of preexisting immunity to AdH5.",,"['Sridhar, S.', 'Reyes-Sandoval, A.', 'Draper, S. J.', 'Moore, A. C.', 'Gilbert, S. C.', 'Gao, G. P.', 'Wilson, J. M.', 'Hill, A. V. S.']",,,,
,PMC,An Overview of Patent Law as Applied to the Field of Veterinary Medicine,http://dx.doi.org/10.1208/s12248-007-9005-4,PMC2751450,,,This article analyzes some of the challenges that can arise when patent law is applied to the field of veterinary medicine. Topics covered in this article include an overview of the different kinds of inventions that can be patented in the veterinary field; a review of recent legal developments that may affect the patenting of veterinary pharmaceuticals; a discussion of some potential issues related to patents covering assays; and an identification of some special situations where the law affecting veterinary pharmaceuticals is actually different from the law affecting human pharmaceuticals.,,"Gould, James M.",,,,
,PMC,Current and future antiviral therapy of severe seasonal and avian influenza,http://dx.doi.org/10.1016/j.antiviral.2008.01.003,PMC2346583,,,"The currently circulating H3N2 and H1N1 subtypes of influenza A virus cause a transient, febrile upper respiratory illness in most adults and children (“seasonal influenza”), but infants, the elderly, immunodeficient and chronically ill persons may develop life-threatening primary viral pneumonia or complications such as bacterial pneumonia. By contrast, avian influenza viruses such as the H5N1 virus that recently emerged in Southeast Asia can cause severe disease when transferred from birds to previously healthy people (“avian influenza”). Most H5N1 patients present with fever, cough and shortness of breath that progress rapidly to adult respiratory distress syndrome. In seasonal influenza, viral replication remains confined to the respiratory tract, but limited studies indicate that H5N1 infections are characterized by systemic viral dissemination, high cytokine levels and multiorgan failure. Gastrointestinal infection and encephalitis also occur. The licensed anti-influenza drugs (the M2 ion channel blockers, amantadine and rimantadine, and the neuraminidase inhibitors, oseltamivir and zanamivir) are beneficial for uncomplicated seasonal influenza, but appropriate dosing regimens for severe seasonal or H5N1 viral infections have not been defined. Treatment options may be limited by the rapid emergence of drug-resistant viruses. Ribavirin has also been used to a limited extent to treat influenza. This article reviews approaches to therapy, including licensed drugs and treatments under development, including high-dose oseltamivir; parenterally administered neuraminidase inhibitors, peramivir and zanamivir; dimeric forms of zanamivir; the RNA polymerase inhibitor T-705; a ribavirin prodrug, viramidine; polyvalent and monoclonal antibodies; and combination therapies.",,"['Beigel, John', 'Bray, Mike']",,,,
,PMC,Priming with rAAV encoding RBD of SARS-CoV S protein and boosting with RBD-specific peptides for T cell epitopes increase T cell responses and provide protection against SRAS-CoV infection,http://dx.doi.org/10.1016/j.vaccine.2008.01.025,PMC2600875,,,"Development of vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is crucial in the prevention of SARS reemergence. The receptor-binding domain (RBD) of SARS-CoV spike (S) protein is an important target in developing safe and effective SARS vaccines. Our previous study has demonstrated that vaccination with adeno-associated virus encoding RBD (RBD-rAAV) induces high titer of neutralizing antibodies. In this study, we further assessed the immune responses and protective effect of the immunization with RBD-rAAV prime/RBD-specific T cell peptide boost, as compared to those of vaccinations with RBD-rAAV and RBD-peptides alone. Our results indicated that RBD-rAAV prime/RBD-peptide boost induced similar Th1 and neutralizing antibody responses, but stronger Th2 and CTL responses than RBD-rAAV prime/boost. The resulting immune responses protected the vaccinated mice from subsequent SARS-CoV challenge, which was evidenced by lower level of viral replication in mouse lung tissues. However, no significant immune responses and protective effect were detected in mice vaccinated with RBD-peptides or blank AAV alone. Since T cell epitopes are highly conserved and boosting with peptides may induce the production of effector memory T cells, our results suggest that the vaccination protocol used may be ideal for providing effective, universal and long-term protection against SARS-CoV infection.",,"['Du, Lanying', 'Zhao, Guangyu', 'Lin, Yongping', 'Chan, Chris CS', 'He, Yuxian', 'Jiang, Shibo', 'Wu, Changyou', 'Jin, Dong-Yan', 'Yuen, Kwok-Yung', 'Zhou, Yusen', 'Zheng, Bo-Jian']",,,,
,PMC,Relative Immunogenicity and Protection Potential of Candidate Yersinia Pestis Antigens against Lethal Mucosal Plague Challenge in Balb/C Mice,http://dx.doi.org/10.1016/j.vaccine.2008.01.024,PMC2288748,,,"Yersinia Pestis Outer proteins, plasminogen activator protease and Yop secretion protein F are necessary for the full virulence of Yesinia pestis and have been proposed as potential protective antigens for vaccines against plague. In the current study, we used DNA immunization as a tool to study the relative protective immunity of these proteins with a standardized intranasal challenge system in mice. While the natural full length gene sequences for most of these Y. pestis proteins did not display a good level of protein expression in vitro when delivered by a DNA vaccine vector, the overall immunogenicity of these wild type gene DNA vaccines was low in eliciting antigen-specific antibody responses and gene sequence modifications improved both of these parameters. However, even modified YopD, YopO and YscF antigens were only able to partially protect immunized mice at various levels against lethal challenge with Y. pestis KIM 1001 strain while no protection was observed with either the YopB or Pla antigens. These results demonstrate that DNA immunization is effective in screening, optimizing and comparing optimal antigen designs and immunogenicity of candidate antigens for the development of a subunit-based plague vaccine.",,"['Wang, Shixia', 'Joshi, Swati', 'Mboudjeka, Innocent', 'Liu, Fangjun', 'Ling, Tzufan', 'Goguen, Jon D.', 'Lu, Shan']",,,,
,PMC,Structural lability in stem-loop 1 drives a 5' UTR-3' UTR interaction in coronavirus replication,http://dx.doi.org/10.1016/j.jmb.2008.01.068,PMC2652258,,,"The leader RNA of the 5' untranslated region (UTR) of coronaviral genomes contains two stem-loop structures denoted SL1 and SL2. Herein, we show that SL1 is functionally and structurally bipartite. While the upper region of SL1 is required to be paired, we observe strong genetic selection against viruses that contain a deletion of A35, an extrahelical nucleotide that destabilizes SL1, in favor of genomes that contain a diverse panel of destabilizing second-site mutations, due to introduction of a non-canonical base pair near A35. Viruses containing destabilizing SL1-ΔA35 mutations also contain one of two specific mutations in the 3' UTR. Thermal denaturation and imino proton solvent exchange experiments reveal that the lower half of SL1 is unstable and that second-site SL1-ΔA35 substitutions are characterized by one or more features of the wild-type SL1. We propose a ""dynamic SL1"" model, in which the base of SL1 has an optimized lability required to mediate a physical interaction between the 5' and 3' UTRs that stimulates subgenomic RNA synthesis. Although not conserved at the nucleotide sequence level, these general structural characteristics of SL1 appear to be conserved in other coronaviral genomes.",,"['Li, Lichun', 'Kang, Hyojeung', 'Liu, Pinghua', 'Makkinje, Nick', 'Williamson, Shawn T.', 'Leibowitz, Julian L.', 'Giedroc, David P.']",,,,
,PMC,Building Global Health Through a Center-Without-Walls: The Vanderbilt Institute for Global Health,http://dx.doi.org/10.1097/ACM.0b013e318160b76c,PMC2564795,,,"The Institute for Global Health at Vanderbilt enables the expansion and coordination of global health research, service, and training, reflecting the university's commitment to improve health services and outcomes in resource-limited settings. Global health encompasses both prevention via public health and treatment via medical care, all nested within a broader community-development context. This has fostered university-wide collaborations to address education, business/economics, engineering, nursing, and language training, among others. The institute is a natural facilitator for team building and has been especially helpful in organizing institutional responses to global health solicitations from the National Institutes of Health (NIH), Centers for Disease Control (CDC), and other funding agencies. This center-without-walls philosophy nurtures noncompetitive partnerships among and within departments and schools. With extramural support from the NIH and from endowment and developmental investments from the school of medicine, the institute funds new pilot projects to nurture global educational and research exchanges related to health and development. Vanderbilt's newest programs are a CDC-supported HIV/AIDS service initiative in Africa and an overseas research training program for health science graduate students and clinical fellows. New opportunities are available for Vanderbilt students, staff, and faculty to work abroad in partnership with international health projects through a number of Tennessee institutions now networked with the institute. A center-without-walls may be a model for institutions contemplating strategic investments to better organize service and teaching opportunities abroad, and to achieve greater successes in leveraging extramural support for overseas and domestic work focused on tropical medicine and global health.",,"['Vermund, Sten H.', 'Sahasrabuddhe, Vikrant V.', 'Khedkar, Sheetal', 'Jia, Yujiang', 'Etherington, Carol', 'Vergara, Alfredo']",,,,
,PMC,Applying Rapid Genome Sequencing technologies to Characterize Pathogen Genomes: Innovations in DNA sequencing shed light on pathogen genomes,,PMC5628356,,,,,"['Steinberg, Karyn Meltz', 'Okou, David T.', 'Zwick, Michael E.']",,,,
,PMC,Ethical planning for an influenza pandemic,http://dx.doi.org/10.7861/clinmedicine.8-1-49,PMC4953709,,,"A UK Pandemic Influenza Contingency Plan was developed in 2006 but little research has since been carried out as to how ethically acceptable it will be to society. A survey containing two hypothetical scenarios was distributed to 1,018 hospital staff. The survey considered their attitudes to the professional and ethical responsibilities of healthcare workers, and to resource allocation on the intensive care unit (ICU). Of those distributed, 406 (40%) surveys were returned. During a pandemic, 320 (79%) healthcare professionals would continue to work and 339 (83%) felt it would be unprofessional for doctors to leave work. Only 218 (54%) chose the same patient for the last ICU bed. Most staff surveyed felt they should (professionally) and would (voluntarily) work during a pandemic despite high personal risk. A wide diversity of opinion existed regarding resource allocation of ICU beds. These ethical issues require open debate to ensure UK pandemic plans are ethically acceptable and practically applicable.",,"['Barr, HL', 'Macfarlane, JT', 'Macgregor, O', 'Foxwell, R', 'Buswell, V', 'Lim, WS']",,,,
,PMC,Musashi1 RNA-Binding Protein Regulates Oligodendrocyte Lineage Cell Differentiation and Survival,http://dx.doi.org/10.1002/glia.20615,PMC2663423,,,"Expression of Musashi1 (Msi1), an evolutionarily conserved RNA-binding protein, in neural stem cells of the subventricular zone in the postnatal and adult CNS indicates a potential role in the generation of oligodendrocytes. We now show Msi1 expression in a subset of oligodendrocyte progenitor (OP) cells in white matter areas temporally and spatially associated with oligodendrogenesis in the postnatal CNS. Msi1 function was evaluated by infection of OP cells with retroviral transduction of Msi1 or knockdown of endogenous Msi1. Retroviral expression of Msi1 significantly reduced the proportion of mature oligodendrocytes generated from OP cells in vitro and in vivo during myelination. Msi1 transduction also promoted OP survival, particularly under conditions of challenge from oxidative stress, while Msi1 siRNA knockdown resulted in dramatic OP cell death. Furthermore, in experimental demyelination Msi1 expression was increased among cells associated with lesions, including OP cells, indicating a potential role in the generation of remyelinating oligodendrocytes.",,"['Dobson, Nicole R.', 'Zhou, Yong-Xing', 'Flint, Nicole C.', 'Armstrong, Regina C.']",,,,
,PMC,Why Examining the Desirability of Health Technology Matters,,PMC2645152,,,"Although technology is ubiquitous in healthcare, its impact on people's perceptions and lives is poorly understood. Fresh insights are required to meet current and future technology-related policy challenges. Keeping a population healthy requires considering not only technologies that are used in clinical settings (diagnostic, therapeutic, palliative), but also those used in the community (home care, self-care, technical aids) and those that affect health more broadly (health promotion technologies, occupational health technologies). At the policy making level, understanding the desirability of health technology may prove to be more important than simply appraising its affordability.",,"Lehoux, Pascale",,,,
,PMC,Emergency Planning in Ontario's Acute Care Hospitals: A Survey of Board Chairs,,PMC2645143,,,"BACKGROUND: Effective hospital governance depends on proactive board leadership to minimize risk. STUDY AIM: To survey hospital board chairs about governance practices, particularly with respect to approval processes for oversight of management preparedness for unforeseen emergencies. METHODS: A 2004 survey of hospital managers initially suggested greater board leadership in risk management as a desired strategic priority for Ontario's acute care hospitals. Our literature review and panel process defined 34 best practices in board governance, including two practices explicitly addressing the board's role in preparing for risk. RESULTS: Our findings revealed that some boards may not be actively engaged in ensuring that adequate processes are in place to protect against risk. More than one-quarter (n=28, 26.9%) of board chairs reported that they had not approved a management plan to address emergencies. Thirty respondents (28.8%) said they had not approved a process to identify, manage and minimize risks to the hospital's sustainability. Forty-seven respondents (45.2%) said they had not approved both of these two processes. A significant association emerged between boards that had approved both risk preparation strategies and boards that had implemented six key governance practices relating to accountability for leadership and stakeholder communication.",,"['Seeman, Neil', 'Baker, G. Ross', 'Brown, Adalsteinn D.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.02709-07,PMC2258701,,,,,,,,,
,PMC,Protein production and purification,http://dx.doi.org/10.1038/nmeth.f.202,PMC3178102,,,"In selecting a method to produce a recombinant protein, a researcher is faced with a bewildering array of choices as to where to start. To facilitate decision-making, we describe a consensus ‘what to try first’ strategy based on our collective analysis of the expression and purification of over 10,000 different proteins. This review presents methods that could be applied at the outset of any project, a prioritized list of alternate strategies and a list of pitfalls that trip many new investigators.",,"[None, None, None, None, None, None, None, None, None, None, None, None, None, None]",,,,
,PMC,Integrating genetic and epidemiological data to determine transmission pathways of foot-and-mouth disease virus,http://dx.doi.org/10.1098/rspb.2007.1442,PMC2599933,,,"Estimating detailed transmission trees that reflect the relationships between infected individuals or populations during a disease outbreak often provides valuable insights into both the nature of disease transmission and the overall dynamics of the underlying epidemiological process. These trees may be based on epidemiological data that relate to the timing of infection and infectiousness, or genetic data that show the genetic relatedness of pathogens isolated from infected individuals. Genetic data are becoming increasingly important in the estimation of transmission trees of viral pathogens due to their inherently high mutation rate. Here, we propose a maximum-likelihood approach that allows epidemiological and genetic data to be combined within the same analysis to infer probable transmission trees. We apply this approach to data from 20 farms infected during the 2001 UK foot-and-mouth disease outbreak, using complete viral genome sequences from each infected farm and information on when farms were first estimated to have developed clinical disease and when livestock on these farms were culled. Incorporating known infection links due to animal movement prior to imposition of the national movement ban results in the reduction of the number of trees from 41 472 that are consistent with the genetic data to 1728, of which just 4 represent more than 95% of the total likelihood calculated using a model that accounts for the epidemiological data. These trees differ in several ways from those constructed prior to the availability of genetic data.",,"['Cottam, Eleanor M', 'Thébaud, Gaël', 'Wadsworth, Jemma', 'Gloster, John', 'Mansley, Leonard', 'Paton, David J', 'King, Donald P', 'Haydon, Daniel T']",,,,
,PMC,THE SARS-COV FERRET MODEL IN AN INFECTION-CHALLENGE STUDY,http://dx.doi.org/10.1016/j.virol.2007.12.032,PMC2831213,,,"Phase I human clinical studies involving therapeutics for emerging and biodefense pathogens with low incidence, such as the severe acute respiratory syndrome coronavirus (SARS-CoV), requires at a minimum preclinical evaluation of efficacy in two well-characterized and robust animal models. Thus, a ferret SARS-CoV model was evaluated over a period of 58 days following extensive optimization and characterization of the model in order to validate clinical, histopathological, virological and immunological endpoints. Ferrets that were infected intranasally with 10(3) TCID(50) SARS-CoV showed higher body temperature (2–6 d.p.i.), sneezing (5–10 d.p.i.), lesions (5–7 d.p.i.) and decreased WBC/lymphocytes (2–5 d.p.i.). SARS-CoV was detected up to 7 d.p.i. in various tissues and excreta, while neutralizing antibody titers rose at 7 d.p.i. and peaked at 14 d.p.i. At 29 d.p.i., one group was challenged with 10(3) TCID(50) SARS-CoV, and an anamnestic response in neutralizing antibodies was evident with no detectable virus. This study supports the validity of the ferret model for use in evaluating efficacy of potential therapeutics to treat SARS.",,"['Chu, Yong-Kyu', 'Ali, Georgia D.', 'Jia, Fuli', 'Li, Qianjun', 'Kelvin, David', 'Couch, Ronald C.', 'Harrod, Kevin S.', 'Hutt, Julie A.', 'Cameron, Cheryl', 'Weiss, Susan R.', 'Jonsson, Colleen B.']",,,,
,PMC,Electron Cryomicroscopy Reveals Different F1+F2 Protein States in Intact Parainfluenza Virions,http://dx.doi.org/10.1128/JVI.02154-07,PMC2268498,,,"Electron cryomicrographs of intact parainfluenza virus 5 (PIV5) virions revealed two different surface structures, namely, a continuous layer and distinct individual spikes. The structure of these spikes reconstructed from intact virions was compared with known F ectodomain structures and was found to be different from the prefusion PIV5 F0 structure but, surprisingly, very similar to the human PIV3 F postfusion structure. Hence, we conclude that the individual F1+F2 spikes in intact PIV5 virions also correspond to the postfusion state. Since the observed fusion activity of PIV5 virions has to be associated with prefusion F1+F2 proteins, they have necessarily to be localized in the continuous surface structure. The data therefore strongly suggest that the prefusion state of the F1+F2 protein requires stabilization, most probably by the association with hemagglutinin-neuraminidase. The conversion of F1+F2 proteins from the prefusion toward the postfusion state while embedded in the virus membrane is topologically difficult to comprehend on the basis of established models and demands reconsideration of our current understanding.",,"['Ludwig, Kai', 'Schade, Boris', 'Böttcher, Christoph', 'Korte, Thomas', 'Ohlwein, Nina', 'Baljinnyam, Bolormaa', 'Veit, Michael', 'Herrmann, Andreas']",,,,
,PMC,Proteolytic Cleavage of VP1-2 Is Required for Release of Herpes Simplex Virus 1 DNA into the Nucleus,http://dx.doi.org/10.1128/JVI.01919-07,PMC2268474,,,"In this report we propose a model in which after the herpes simplex virus (HSV) capsid docks at the nuclear pore, the tegument protein attached to the capsid must be cleaved by a serine or a cysteine protease in order for the DNA to be released into the nucleus. In support of the model are the following results. (i) Exposure of cells at the time of or before infection to l-(tosylamido-2-phenyl) ethyl chloromethyl ketone (TPCK), a serine-cysteine protease inhibitor, prevents the release of viral DNA or expression of viral genes. TPCK does not block viral gene expression after entry of viral DNA into the nucleus. (ii) The tegument protein VP1-2, the product of the U(L)36 gene, is cleaved shortly after the entry of the HSV 1 (HSV-1) virion into the cell. (iii) The proteolytic cleavage of VP1-2 does not occur in cells that are infected with HSV-1 under conditions that prevent the release of the viral DNA into the nucleus. (iv) The proteolytic cleavage of VP1-2 occurs only after the capsid is attached to the nuclear pore. Thus, TPCK prevented the release of HSV-1 DNA into the nucleus when added to medium 1 hour after infection with tsB7 at 39.5°C followed by a shift down to the permissive temperature. The ts lesion maps in the U(L)36 gene. At the nonpermissive temperature, the capsids accumulate at the nuclear pore but the DNA is not released into the nucleus.",,"['Jovasevic, Vladimir', 'Liang, Li', 'Roizman, Bernard']",,,,
,PMC,Functional Analysis of the Transmembrane (TM) Domain of the Autographa californica Multicapsid Nucleopolyhedrovirus GP64 Protein: Substitution of Heterologous TM Domains,http://dx.doi.org/10.1128/JVI.02104-07,PMC2268458,,,"GP64, the major envelope glycoprotein of the Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) budded virion, is important for host cell receptor binding and mediates low-pH-triggered membrane fusion during entry by endocytosis. In the current study, we examined the functional role of the AcMNPV GP64 transmembrane (TM) domain by replacing the 23-amino-acid GP64 TM domain with corresponding TM domain sequences from a range of viral and cellular type I membrane proteins, including Orgyia pseudotsugata MNPV (OpMNPV) GP64 and F, thogotovirus GP75, Lymantria dispar MNPV (LdMNPV) F, human immunodeficiency virus type 1 (HIV-1) GP41, human CD4 and glycophorin A (GpA), and influenza virus hemagglutinin (HA), and with a glycosylphosphatidylinositol (GPI) anchor addition sequence. In transient expression experiments with Sf9 cells, chimeric GP64 proteins containing either a GPI anchor or TM domains from LdMNPV F or HIV-1 GP41 failed to localize to the cell surface and thus appear to be incompatible with either GP64 structure or cell transport. All of the mutant constructs detected at the cell surface mediated hemifusion (outer leaflet merger) upon low-pH treatment, but only those containing TM domains from CD4, GpA, OpMNPV GP64, and thogotovirus GP75 mediated pore formation and complete membrane fusion activity. This supports a model in which partial fusion (hemifusion) proceeds by a mechanism that is independent of the TM domain and the TM domain participates in the enlargement or expansion of fusion pores after hemifusion. GP64 proteins containing heterologous TM domains mediated virion budding with dramatically differing levels of efficiency. In addition, chimeric GP64 proteins containing TM domains from CD4, GpA, HA, and OpMNPV F were incorporated into budded virions but were unable to rescue the infectivity of a gp64 null virus, whereas those with TM domains from OpMNPV GP64 and thogotovirus GP75 rescued infectivity. These results show that in addition to its basic role in membrane anchoring, the GP64 TM domain is critically important for GP64 trafficking, membrane fusion, virion budding, and virus infectivity. These critical functions were replaced only by TM domains from related viral membrane proteins.",,"['Li, Zhaofei', 'Blissard, Gary W.']",,,,
,PMC,"Inhibition of Human Immunodeficiency Virus Type 1 Replication in Human Cells by Debio-025, a Novel Cyclophilin Binding Agent",http://dx.doi.org/10.1128/AAC.01324-07,PMC2292519,,,"Debio-025 is a synthetic cyclosporine with no immunosuppressive capacity but a high inhibitory potency against cyclophilin A (CypA)-associated cis-trans prolyl isomerase (PPIase) activity. A lack of immunosuppressive effects compared to that of cyclosporine was demonstrated both in vitro and in vivo. For three cyclosporines, the inhibitory potential against PPIase activity was quantitatively correlated with that against human immunodeficiency virus type 1 (HIV-1) replication. Debio-025 selectively inhibited the replication of HIV-1 in a CD4(+) cell line and in peripheral blood mononuclear cells: potent activity was demonstrated against clinical isolates of various HIV-1 subtypes, including isolates with multidrug resistance to reverse transcriptase and protease inhibitors. Simian immunodeficiency virus and HIV-2 strains were generally resistant to inhibition by Debio-025; however, some notable exceptions of sensitive HIV-2 clinical isolates were detected. In two-drug combination studies, additive inhibitory effects were found between Debio-025 and 19 clinically used drugs of different classes. Clinical HIV-1 isolates that are naturally resistant to Debio-025 and that do not depend on CypA for infection were identified. Comparison of the amino acid sequences of the CypA binding domain of the capsid (CA) protein from Debio-025-sensitive and -resistant HIV-1 isolates indicated that resistance was mostly associated with an H87Q/P exchange. Mechanistically, cyclosporines competitively inhibit the binding of CypA to the HIV-1 CA protein, which is an essential interaction required for early steps in HIV-1 replication. By real-time PCR we demonstrated that early reverse transcription is reduced in the presence of Debio-025 and that late reverse transcription is almost completely blocked. Thus, Debio-025 seems to interfere with the function of CypA during the progression/completion of HIV-1 reverse transcription.",,"['Ptak, Roger G.', 'Gallay, Philippe A.', 'Jochmans, Dirk', 'Halestrap, Andrew P.', 'Ruegg, Urs T.', 'Pallansch, Luke A.', 'Bobardt, Michael D.', 'de Béthune, Marie-Pierre', 'Neyts, Johan', 'De Clercq, Erik', 'Dumont, Jean-Maurice', 'Scalfaro, Pietro', 'Besseghir, Kamel', 'Wenger, Roland M.', 'Rosenwirth, Brigitte']",,,,
,PMC,Spreading of sexually transmitted diseases in heterosexual populations,http://dx.doi.org/10.1073/pnas.0707332105,PMC2234155,,,"The spread of sexually transmitted diseases (e.g., chlamydia, syphilis, gonorrhea, HIV, etc.) across populations is a major concern for scientists and health agencies. In this context, both the data collection on sexual contact networks and the modeling of disease spreading are intensive contributions to the search for effective immunization policies. Here, the spreading of sexually transmitted diseases on bipartite scale-free graphs, representing heterosexual contact networks, is considered. We analytically derive the expression for the epidemic threshold and its dependence with the system size in finite populations. We show that the epidemic outbreak in bipartite populations, with number of sexual partners distributed as in empirical observations from national sex surveys, takes place for larger spreading rates than for the case in which the bipartite nature of the network is not taken into account. Numerical simulations confirm the validity of the theoretical results. Our findings indicate that the restriction to crossed infections between the two classes of individuals (males and females) has to be taken into account in the design of efficient immunization strategies for sexually transmitted diseases.",,"['Gómez-Gardeñes, Jesús', 'Latora, Vito', 'Moreno, Yamir', 'Profumo, Elio']",,,,
,PMC,Evolution of feline immunodeficiency virus in Felidae: Implications for human health and wildlife ecology,http://dx.doi.org/10.1016/j.vetimm.2008.01.010,PMC2774529,,,"Genetic analyses of feline immunodeficiency viruses provide significant insights on the worldwide distribution and evolutionary history of this emerging pathogen. Large-scale screening of over 3000 samples from all species of Felidae indicates that at least some individuals from most species possess antibodies that cross react to FIV. Phylogenetic analyses of genetic variation in the pol-RT gene demonstrate that FIV lineages are species-specific and suggest that there has been a prolonged period of viral-host co-evolution. The clinical effects of FIV specific to species other than domestic cat are controversial. Comparative genomic analyses of all full-length FIV genomes confirmed that FIV is host specific. Recently sequenced lion subtype E is marginally more similar to Pallas cat FIV though env is more similar to that of domestic cat FIV, indicating a possible recombination between two divergent strains in the wild. Here we review global patterns of FIV seroprevalence and endemnicity, assess genetic differences within and between species-specific FIV strains, and interpret these with patterns of felid speciation to propose an ancestral origin of FIV in Africa followed by interspecies transmission and global dissemination to Eurasia and the Americas. Continued comparative genomic analyses of full-length FIV from all seropositive animals, along with whole genome sequence of host species, will greatly advance our understanding of the role of recombination, selection and adaptation in retroviral emergence.",,"['Pecon-Slattery, Jill', 'Troyer, Jennifer L.', 'Johnson, Warren E.', 'O’Brien, Stephen J.']",,,,
,PMC,FIV cross-species transmission: an evolutionary prospective,http://dx.doi.org/10.1016/j.vetimm.2008.01.023,PMC2442884,,,"Feline and primate immunodeficiency viruses (FIVs, SIVs, and HIV) are transmitted via direct contact (e.g. fighting, sexual contact, and mother-offspring transmission). This dynamic likely poses a behavioral barrier to cross-species transmission in the wild. Recently, several host intracellular anti-viral proteins that contribute to species-specificity of primate lentiviruses have been identified revealing adaptive mechanisms that further limit spread of lentiviruses between species. Consistent with these inter-species transmission barriers, phylogenetic evidence supports the prediction that FIV transmission is an exceedingly rare event between free-ranging cat species, though it has occurred occasionally in captive settings. Recently we documented that puma and bobcats in Southern California share an FIV strain, providing an opportunity to evaluate evolution of both viral strains and host intracellular restriction proteins. These studies are facilitated by the availability of the 2X cat genome sequence annotation. In addition, concurrent viral and host genetic analyses have been used to track patterns of migration of the host species and barriers to transmission of the virus within the African lion. These studies illustrate the utility of FIV as a model to discover the variables necessary for establishment and control of lentiviral infections in new species.",,"['Troyer, Jennifer L.', 'VandeWoude, Sue', 'Pecon-Slattery, Jill', 'McIntosh, Carl', 'Franklin, Sam', 'Antunes, Agostinho', 'Johnson, Warren', ""O'Brien, Stephen J.""]",,,,
,PMC,A Genome-Wide Expression Analysis in Blood Identifies Pre-Elafin as a Biomarker in ARDS,http://dx.doi.org/10.1165/rcmb.2007-0354OC,PMC2396250,,,"Previous microarray-based studies of acute respiratory distress syndrome (ARDS) were performed using various models to mimic disease pathogenesis. The complexity of the pathophysiologic response to direct or indirect lung injury in ARDS is difficult to reconstruct in experimental conditions. Thus, direct analysis of ARDS patient blood may provide valuable information. We investigated genome-wide gene expression profiles in paired whole blood samples from patients with ARDS (n = 8) during the acute stage (within 3 d of diagnosis) and recovery stage of ARDS (around ICU discharge). Among 126 differentially expressed genes, peptidase inhibitor 3 (PI3, encoding elafin, a potent neutrophil elastase inhibitor) had the largest fold-change (−3-fold changes, acute stage/recovery stage) in expression, indicating down-regulation during the acute stage of ARDS. We further examined plasma PI3 levels in 40 patients with ARDS and 23 at-risk control subjects from the same cohort. There was a coincidence of the microarray findings of lower PI3 gene expression with the lower plasma PI3 during the acute-stage. The plasma PI3 levels were statistically significant different among pre-diagnosis, day of diagnosis, and post-diagnosis groups (ANOVA, P = 0.001), with a trend of decreasing from pre- to post-diagnosis group. The time course of plasma PI3 decrease is well correlated with the course of early ARDS development (Pearson correlation coefficient: −0.52, P = 0.0006). Considering that PI3 can covalently binding to extracellular matrix in lung, circulating PI3 may provide a useful clinical marker for monitoring the early development of ARDS and may have implications for ARDS treatment.",,"['Wang, Zhaoxi', 'Beach, Douglas', 'Su, Li', 'Zhai, Rihong', 'Christiani, David C.']",,,,
,PMC,Sequential affinity purification of peroxidase tagged bispecific anti-SARS-CoV antibodies on phenylboronic acid agarose,http://dx.doi.org/10.1016/j.jchromb.2008.01.003,PMC2678934,,,"Hybrid hybridomas (quadromas) are derived by fusing at least two hybridomas, each producing a different antibody of predefined specificity. The resulting cell secretes not only the immunoglobulins of both parents but also hybrid molecules manifesting the binding characteristics of the individual fusion partners. Purification of the desired bispecific immunoprobe with high specific activity from a mixture of bispecific and monospecific monoclonal antibodies requires special strategies. Using a dual, sequential affinity chromatography (Protein-G chromatography followed by m-aminophenyleboronic acid agarose column), we have purified bispecific monoclonal antibodies (BsMAb) as a preformed HRPO (Horseradish Peroxidase) complex (BsMAb–HRPO). The quadroma culture supernatant was initially processed on a Protein-G column to isolate all the species of immunoglobulins. This pre-enriched fraction was subsequently passed through the aminophenyleboronic acid column super saturated with HRPO. The column matrix has the ability to bind to proteins such as HRPO with vicinal diols. The enzyme loaded column captures the desired bispecific anti-SARS-CoV × anti-HRPO species with the elimination of the monospecific anti-SARS-CoV MAb to result in a high specific activity diagnostic probe. The presence of anti-HRPO MAb is an acceptable impurity as it will not bind to the target SARS-CoV NP antigen and will get washed out during the ELISA procedure.",,"['Bhatnagar, Pravin K.', 'Das, Dipankar', 'Suresh, Mavanur R.']",,,,
,PMC,Structural Basis for Potent Cross-Neutralizing Human Monoclonal Antibody Protection against Lethal Human and Zoonotic Severe Acute Respiratory Syndrome Coronavirus Challenge,http://dx.doi.org/10.1128/JVI.02377-07,PMC2268459,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002, and detailed phylogenetic and epidemiological analyses have suggested that it originated from animals. The spike (S) glycoprotein has been identified as a major component of protective immunity, and 23 different amino acid changes were noted during the expanding epidemic. Using a panel of SARS-CoV recombinants bearing the S glycoproteins from isolates representing the zoonotic and human early, middle, and late phases of the epidemic, we identified 23 monoclonal antibodies (MAbs) with neutralizing activity against one or multiple SARS-CoV spike variants and determined the presence of at least six distinct neutralizing profiles in the SARS-CoV S glycoprotein. Four of these MAbs showed cross-neutralizing activity against all human and zoonotic S variants in vitro, and at least three of these were mapped in distinct epitopes using escape mutants, structure analyses, and competition assays. These three MAbs (S109.8, S227.14, and S230.15) were tested for use in passive vaccination studies using lethal SARS-CoV challenge models for young and senescent mice with four different homologous and heterologous SARS-CoV S variants. Both S227.14 and S230.15 completely protected young and old mice from weight loss and virus replication in the lungs for all viruses tested, while S109.8 completely protected mice from weight loss and clinical signs in the presence of viral titers. We conclude that a single human MAb can confer broad protection against lethal challenge with multiple zoonotic and human SARS-CoV isolates, and we identify a robust cocktail formulation that targets distinct epitopes and minimizes the likely generation of escape mutants.",,"['Rockx, Barry', 'Corti, Davide', 'Donaldson, Eric', 'Sheahan, Timothy', 'Stadler, Konrad', 'Lanzavecchia, Antonio', 'Baric, Ralph']",,,,
,PMC,Aromatic Amino Acids in the Juxtamembrane Domain of Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Are Important for Receptor-Dependent Virus Entry and Cell-Cell Fusion,http://dx.doi.org/10.1128/JVI.01805-07,PMC2258972,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) spike glycoprotein (S) is a class I viral fusion protein that binds to its receptor glycoprotein, human angiotensin converting enzyme 2 (hACE2), and mediates virus entry and cell-cell fusion. The juxtamembrane domain (JMD) of S is an aromatic amino acid-rich region proximal to the transmembrane domain that is highly conserved in all coronaviruses. Alanine substitutions for one or two of the six aromatic residues in the JMD did not alter the surface expression of the SARS-CoV S proteins with a deletion of the C-terminal 19 amino acids (S Δ19) or reduce binding to soluble human ACE2 (hACE2). However, hACE2-dependent entry of trypsin-treated retrovirus pseudotyped viruses expressing JMD mutant S Δ19 proteins was greatly reduced. Single alanine substitutions for aromatic residues reduced entry to 10 to 60% of the wild-type level. The greatest reduction was caused by residues nearest the transmembrane domain. Four double alanine substitutions reduced entry to 5 to 10% of the wild-type level. Rapid hACE2-dependent S-mediated cell-cell fusion was reduced to 60 to 70% of the wild-type level for all single alanine substitutions and the Y1188A/Y1191A protein. S Δ19 proteins with other double alanine substitutions reduced cell-cell fusion further, from 40% to less than 20% of wild-type levels. The aromatic amino acids in the JMD of the SARS-CoV S glycoprotein play critical roles in receptor-dependent virus-cell and cell-cell fusion. Because the JMD is so highly conserved in all coronavirus S proteins, it is a potential target for development of drugs that may inhibit virus entry and/or cell-cell fusion mediated by S proteins of all coronaviruses.",,"['Howard, Megan W.', 'Travanty, Emily A.', 'Jeffers, Scott A.', 'Smith, M. K.', 'Wennier, Sonia T.', 'Thackray, Larissa B.', 'Holmes, Kathryn V.']",,,,
,PMC,Expression of Transgenes from Newcastle Disease Virus with a Segmented Genome,http://dx.doi.org/10.1128/JVI.02341-07,PMC2258964,,,"Paramyxoviruses belong to the Paramyxoviridae family of the order Mononegavirales. They have a nonsegmented negative-stranded RNA genome and can cause a number of diseases in humans and animals. We generated a recombinant Newcastle disease virus (NDV) possessing a two-segmented genome. Each genomic segment is flanked by authentic NDV 3′ and 5′ noncoding termini allowing for efficient replication and transcription. A reporter gene encoding green fluorescent protein (GFP) was inserted into one segment, and a red fluorescent protein dsRed gene was inserted into the other segment in order to easily detect the replication and transcription of segments in infected cells. The rescued viruses grew well and were stable in embryonated chicken eggs over multiple passages. We were able to detect the expression of both reporter genes in the same cell infected with the virus possessing a segmented genome, and viral particles can contain either one or two types of RNA segments. We also rescued a two-segmented virus expressing GFP and the severe acute respiratory syndrome-associated coronavirus spike S protein, which is about 200 kDa. The chimeric virus extends the coding capacity of NDV by 30%, suggesting that the two-segmented NDV can be used for development of vaccines or gene therapy vectors carrying long and multiple transgenes.",,"['Gao, Qinshan', 'Park, Man-Seong', 'Palese, Peter']",,,,
,PMC,Intranasal Vaccination of Recombinant Adeno-Associated Virus Encoding Receptor-Binding Domain of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Spike Protein Induces Strong Mucosal Immune Responses and Provides Long-Term Protection against SARS-CoV Infection,,PMC2603051,,,"We have previously reported that a subunit protein vaccine based on the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein and a recombinant adeno-associated virus (rAAV)-based RBD (RBD-rAAV) vaccine could induce highly potent neutralizing Ab responses in immunized animals. In this study, systemic, mucosal, and cellular immune responses and long-term protective immunity induced by RBD-rAAV were further characterized in a BALB/c mouse model, with comparison of the i.m. and intranasal (i.n.) routes of administration. Our results demonstrated that: 1) the i.n. vaccination induced a systemic humoral immune response of comparable strength and shorter duration than the i.m. vaccination, but the local humoral immune response was much stronger; 2) the i.n. vaccination elicited stronger systemic and local specific cytotoxic T cell responses than the i.m. vaccination, as evidenced by higher prevalence of IL-2 and/or IFN-γ-producing CD3(+)/CD8(+) T cells in both lungs and spleen; 3) the i.n. vaccination induced similar protection as the i.m. vaccination against SARS-CoV challenge in mice; 4) higher titers of mucosal IgA and serum-neutralizing Ab were associated with lower viral load and less pulmonary pathological damage, while no Ab-mediated disease enhancement effect was observed; and 5) the vaccination could provide long-term protection against SARS-CoV infection. Taken together, our findings suggest that RBD-rAAV can be further developed into a vaccine candidate for prevention of SARS and that i.n. vaccination may be the preferred route of administration due to its ability to induce SARS-CoV-specific systemic and mucosal immune responses and its better safety profile.",,"['Du, Lanying', 'Zhao, Guangyu', 'Lin, Yongping', 'Sui, Hongyan', 'Chan, Chris', 'Ma, Selene', 'He, Yuxian', 'Jiang, Shibo', 'Wu, Changyou', 'Yuen, Kwok-Yung', 'Jin, Dong-Yan', 'Zhou, Yusen', 'Zheng, Bo-Jian']",,,,
,PMC,"Is the anti-psychotic, 10-(3-(dimethylamino)propyl)phenothiazine (promazine), a potential drug with which to treat SARS infections? Lack of efficacy of promazine on SARS-CoV replication in a mouse model",http://dx.doi.org/10.1016/j.antiviral.2007.12.005,PMC2582943,,,"Phenothiazine and derivatives were tested for inhibition of SARS-CoV replication. Phenothiazine slightly inhibited SARS-CoV replication in a neutral red (NR) uptake assay. Adding a propylamino group to give promazine reduced virus yields (VYR assay) with an EC(90) = 8.3 ± 2.8 µM, but without selectivity. Various substitutions in the basic phenothiazine structure did not promote efficacy. Phenazine ethosulfate was the most potent compound by VYR assay (EC(90) = 6.1 ± 4.3 µM). All compounds were toxic (IC(50) = 6.6–74.5 µM) except for phenoxathiin (IC(50) = 858 ± 208 µM) and 10-(alpha-diethylamino-propionyl) phenothiazine·HCl (IC(50) = 195 ± 71.2 µM). Consequently, none were selective inhibitors of SARS-CoV replication (SI values <1–3.3 µM). These data portended the poor efficacy of promazine in a SARS-CoV mouse lung replication model. Intraperitoneal treatment with promazine using a prophylactic (−4 h)/therapeutic regimen of 1, 10, or 50 mg/(kg day) did not reduce virus lung titers at day 3, yet prolonged virus replication to 14 days. Similar therapeutic promazine doses were not efficacious. Thus, promazine did not affect SARS-CoV replication in vitro or in vivo, nor were any other phenothiazines efficacious in reducing virus replication. Therefore, treating SARS infections with compounds like promazine is not warranted.",,"['Barnard, Dale L.', 'Day, Craig W.', 'Bailey, Kevin', 'Heiner, Matthew', 'Montgomery, Robert', 'Lauridsen, Larry', 'Jung, Kie-Hoon', 'Li, Joseph K.-K.', 'Chan, Paul K.S.', 'Sidwell, Robert W.']",,,,
,PMC,Plasmacytoid dendritic cells and type I IFN: 50 years of convergent history,http://dx.doi.org/10.1016/j.cytogfr.2007.10.006,PMC2277216,,,"It has been 50 years since the initial descriptions of what are now known as plasmacytoid dendritic cells (pDC) and type I IFN. pDC, which are infrequent cells found in the peripheral blood and lymphoid organs, are the most potent producers of type I and type III IFNs in the body. pDC produce IFN-α in response to both DNA and RNA enveloped viruses by virtue of their ribonucleic acids signaling in the endosome through TLR9 and TLR7, respectively. This stimulation, which also occurs with DNA or RNA-containing immune complexes and synthetic TLR7 and −9 agonists, is dependent upon the transcription factor IRF-7, which is expressed at high constitutive levels in pDC. In addition to releasing as much as 3−10 pg of IFN-α/cell, pDC are also potent modulators of the immune response. In this review, we discuss the signaling pathways in pDC, their roles in linking innate and adaptive immunity, and their roles in infectious disease and autoimmunity.",,"['Fitzgerald-Bocarsly, Patricia', 'Dai, Jihong', 'Singh, Sukhwinder']",,,,
,PMC,Importance of Conserved Cysteine Residues in the Coronavirus Envelope Protein,http://dx.doi.org/10.1128/JVI.01914-07,PMC2258990,,,"Coronavirus envelope (E) proteins play an important, not fully understood role(s) in the virus life cycle. All E proteins have conserved cysteine residues located on the carboxy side of the long hydrophobic domain, suggesting functional significance. In this study, we confirmed that mouse hepatitis coronavirus A59 E protein is palmitoylated. To understand the role of the conserved residues and the necessity of palmitoylation, three cysteines at positions 40, 44, and 47 were changed singly and in various combinations to alanine. Double- and triple-mutant E proteins resulted in decreased virus-like particle output when coexpressed with the membrane (M) protein. Mutant E proteins were also studied in the context of a full-length infectious clone. Single-substitution viruses exhibited growth characteristics virtually identical to those of the wild-type virus, while the double-substitution mutations gave rise to viruses with less robust growth phenotypes indicated by smaller plaques and decreased virus yields. In contrast, replacement of all three cysteines resulted in crippled virus with significantly reduced yields. Triple-mutant viruses did not exhibit impairment in entry. Mutant E proteins localized properly in infected cells. A comparison of intracellular and extracellular virus yields suggested that release is only slightly impaired. E protein lacking all three cysteines exhibited an increased rate of degradation compared to that of the wild-type protein, suggesting that palmitoylation is important for the stability of the protein. Altogether, the results indicate that the conserved cysteines and presumably palmitoylation are functionally important for virus production.",,"['Lopez, Lisa A.', 'Riffle, Ambere J.', 'Pike, Steven L.', 'Gardner, Douglas', 'Hogue, Brenda G.']",,,,
,PMC,Envelope Protein Palmitoylations Are Crucial for Murine Coronavirus Assembly,http://dx.doi.org/10.1128/JVI.01906-07,PMC2258982,,,"The coronavirus assembly process encloses a ribonucleoprotein genome into vesicles containing the lipid-embedded proteins S (spike), E (envelope), and M (membrane). This process depends on interactions with membranes that may involve palmitoylation, a common posttranslational lipidation of cysteine residues. To determine whether specific palmitoylations influence coronavirus assembly, we introduced plasmid DNAs encoding mouse hepatitis coronavirus (MHV) S, E, M, and N (nucleocapsid) into 293T cells and found that virus-like particles (VLPs) were robustly assembled and secreted into culture medium. Palmitate adducts predicted on cysteines 40, 44, and 47 of the 83-residue E protein were then evaluated by constructing mutant cDNAs with alanine or glycine codon substitutions at one or more of these positions. Triple-substituted proteins (E.Ts) lacked palmitate adducts. Both native E and E.T proteins localized at identical perinuclear locations, and both copurified with M proteins, but E.T was entirely incompetent for VLP production. In the presence of the E.T proteins, the M protein subunits accumulated into detergent-insoluble complexes that failed to secrete from cells, while native E proteins mobilized M into detergent-soluble secreted forms. Many of these observations were corroborated in the context of natural MHV infections, with native E, but not E.T, complementing debilitated recombinant MHVs lacking E. Our findings suggest that palmitoylations are essential for E to act as a vesicle morphogenetic protein and further argue that palmitoylated E proteins operate by allowing the primary coronavirus assembly subunits to assume configurations that can mobilize into secreted lipid vesicles and virions.",,"['Boscarino, Joseph A.', 'Logan, Hillary L.', 'Lacny, Jason J.', 'Gallagher, Thomas M.']",,,,
,PMC,Effect of notoginsenoside R1 on hepatic microcirculation disturbance induced by gut ischemia and reperfusion,http://dx.doi.org/10.3748/wjg.14.29,PMC2673388,,,"AIM: To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion (I/R) in mice. METHODS: The superior mesenteric artery (SMA) of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-min reperfusion. In another set of experiments, R1 was continuously infused (10 mg/kg per hour) from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell (RBC) velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate transaminase (AST) in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) in plasma were evaluated by flow cytometry. E-selectin and intercellular adhesion molecule-1 (ICAM-1) in hepatic tissue were examined by immunofluorescence. RESULTS: After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1. CONCLUSION: R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury. The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.",,"['Chen, Wei-Xing', 'Wang, Fang', 'Liu, Yu-Ying', 'Zeng, Qing-Jiang', 'Sun, Kai', 'Xue, Xin', 'Li, Xiang', 'Yang, Ji-Ying', 'An, Li-Hua', 'Hu, Bai-He', 'Yang, Jin-Hui', 'Wang, Chuan-She', 'Li, Zhi-Xin', 'Liu, Lian-Yi', 'Li, Yan', 'Zheng, Jun', 'Liao, Fu-Long', 'Han, Dong', 'Fan, Jing-Yu', 'Han, Jing-Yan']",,,,
,PMC,Flowing away: water and health opportunities,http://dx.doi.org/10.2471/BLT.07.049619,PMC2647355,,,,,"Bartram, Jamie",,,,
,PMC,Thailand’s unsung heroes,http://dx.doi.org/10.2471/BLT.08.010108,PMC2647352,,,"The success of primary health care programmes in Thailand over the past three decades can be attributed not only to medical advances but to the role of community health volunteers. Buddhist monks and their temples have been strongly involved in health promotion and education, particularly in remote, rural communities.",,"Treerutkuarkul, Apiradee",,,,
,PMC,The infectious diseases consequences of monkey business,,PMC2610274,,,,,"['Conly, JM', 'Johnston, BL']",,,,
,PMC,Effect of dexamethasone administration on bulls with a localized testicular infection with bovine viral diarrhea virus,,PMC2117368,,,"The objective of this research was to evaluate reactivation of bovine viral diarrhea virus (BVDV) following dexamethasone treatment in 4 bulls that had previously been inoculated with BVDV, 3 of which had been demonstrated to have a localized testicular infection. Bulls were housed in an isolated pasture with in-contact steers. Beginning on day 0 of this study, all bulls received a daily dose of 0.1 mg/kg body weight (BW) of dexamethasone intravenously for 5 consecutive days. Blood was collected from the in-contact steers and semen, blood, and cerebrospinal fluid were collected from the bulls during and following dexamethasone treatment. Samples were assayed for BVDV using virus isolation and reverse transcription-nested polymerase chain reaction (RT-nPCR). Serum was assayed for antibody using standard virus isolation. Virus was not isolated from blood, cerebrospinal fluid, or semen from any of the 4 bulls during the study period. One of the bulls was positive for BVDV in semen by RT-nPCR throughout the study period. The BVDV was not recovered from any in-contact control steers during the 28-day study period, nor did any of the in-contact control steers seroconvert to BVDV. Raw semen from 1 bull that was RT-nPCR positive was intravenously inoculated into 7 seronegative steers based upon the Cornell Semen Test. The BVDV could not be recovered from the steers and none of them seroconverted to BVDV. The results indicated that reactivation of BVDV in bulls with a localized testicular infection is unlikely; however, further research is necessary to determine the full potential for BVDV transmission from bulls with a localized testicular infection.",,"['Walz, Paul H.', 'Givens, M. Daniel', 'Cochran, Anna', 'Navarre, Christine B.']",,,,
,PMC,Receiver operating characteristic-based assessment of a serological test used to detect Johne’s disease in Israeli dairy herds,,PMC2117362,,,"The overall accuracy of an enzyme-linked immunosorbent assay (ELISA) used to detect Johne’s disease at herd level was explored in relation to an imperfect test (fecal culture) in 57 Israeli dairy herds. Receiver-operating characteristic (ROC) analysis indicated an area under the curve (AUC) that corresponded to a test accuracy of 82.0% (69.5% to 90.9%; 95% confidence), with optimized herd sensitivity and herd specificity of 70.4% and 83.3%, respectively; and predictive values of 79.2 (+) and 75.8% (−). The optimal ELISA cutoff was 3.16% (> 3.16% seropositive cows in a herd), which was associated with likelihood ratios (LR) of 4.22 (+LR) and 0.36 (−LR), and post-test probabilities of 0.79 (+) and 0.17 (−). For herds with ≤ 200 cows (n = 19 herds), the 95% confidence interval (CI) for the AUC was 0.62–0.97 and the optimal cutoff was 3.33% (HSe = 87.5, HSp = 81.8); for herds with > 200 but ≤ 270 cows (n = 19 herds), the 95% AUC CI was 0.62–0.97 and the optimal cutoff was 1.13% (HSe = 90.0, HSp = 77.78); and for herds with > 270 cows (n = 19 herds), the 95% AUC CI was 0.69–0.99 and the optimal cutoff was 0.7% (HSe = 100.0, HSp = 70.0). The AUC was not influenced by across-herd prevalence [R(2) (adjusted) = 0.0, P > 0.05]. Findings may be applied to facilitate targeted sampling of herds similar to those evaluated. For instance, a test cutoff of 0.76% could be considered for “ruling disease in,” while a cutoff of 3.7% could be used for “ruling disease out.” Caveats that may influence this analysis are discussed.",,"['Chaffer, Marcelo', 'Rivas, Ariel L.', 'Elad, Daniel', 'Koren, Ori', 'Garazi, Shlomo', 'Chowell, Gerardo', 'Schwager, Steven J.']",,,,
,PMC,Enhanced expression of 70-kilodalton heat shock protein limits cell division in a sepsis-induced model of acute respiratory distress syndrome,http://dx.doi.org/10.1097/01.CCM.0000295473.56522.EF,PMC2668133,,,"OBJECTIVE: Fibrotic changes are initiated early in acute respiratory distress syndrome. This may involve overproliferation of alveolar type II cells. In an animal model of acute respiratory distress syndrome, we have shown that the administration of an adenoviral vector overexpressing the 70-kd heat shock protein (AdHSP) limited pathophysiological changes. We hypothesized that this improvement may be modulated, in part, by an early AdHSP-induced attenuation of alveolar type II cell proliferation. DESIGN: Laboratory investigation. SETTING: Hadassah-Hebrew University and University of Pennsylvania animal laboratories. SUBJECTS: Sprague-Dawley Rats (250 g). INTERVENTIONS: Lung injury was induced in male Sprague-Dawley rats via cecal ligation and double puncture. At the time of cecal ligation and double puncture, we injected phosphate-buffered saline, AdHSP, or AdGFP (an adenoviral vector expressing the marker green fluorescent protein) into the trachea. Rats then received subcutaneous bromodeoxyuridine. In separate experiments, A549 cells were incubated with medium, AdHSP, or AdGFP. Some cells were also stimulated with tumor necrosis factor-α. After 48 hrs, cytosolic and nuclear proteins from rat lungs or cell cultures were isolated. These were subjected to immunoblotting, immunoprecipitation, electrophoretic mobility shift assay, fluorescent immunohistochemistry, and Northern blot analysis. MEASUREMENTS AND MAIN RESULTS: Alveolar type I cells were lost within 48 hrs of inducing acute respiratory distress syndrome. This was accompanied by alveolar type II cell proliferation. Treatment with AdHSP preserved alveolar type I cells and limited alveolar type II cell proliferation. Heat shock protein 70 prevented overexuberant cell division, in part, by inhibiting hyperphosphorylation of the regulatory retinoblastoma protein. This prevented retinoblastoma protein ubiquitination and degradation and, thus, stabilized the interaction of retinoblastoma protein with E2F1, a key cell division transcription factor. CONCLUSIONS: Heat shock protein 70-induced attenuation of cell proliferation may be a useful strategy for limiting lung injury when treating acute respiratory distress syndrome if consistent in later time points.",,"['Bromberg, Zohar', 'Raj, Nichelle', 'Goloubinoff, Pierre', 'Deutschman, Clifford S.', 'Weiss, Yoram G.']",,,,
,PMC,Structures and Mechanisms of Viral Membrane Fusion Proteins: Multiple Variations on a Common Theme,http://dx.doi.org/10.1080/10409230802058320,PMC2649671,,,"Recent work has identified three distinct classes of viral membrane fusion proteins based on structural criteria. In addition, there are at least four distinct mechanisms by which viral fusion proteins can be triggered to undergo fusion-inducing conformational changes. Viral fusion proteins also contain different types of fusion peptides and vary in their reliance on accessory proteins. These differing features combine to yield a rich diversity of fusion proteins. Yet despite this staggering diversity, all characterized viral fusion proteins convert from a fusion-competent state (dimers or trimers, depending on the class) to a membrane-embedded homotrimeric prehairpin, and then to a trimer-of-hairpins that brings the fusion peptide, attached to the target membrane, and the transmembrane domain, attached to the viral membrane, into close proximity thereby facilitating the union of viral and target membranes. During these conformational conversions, the fusion proteins induce membranes to progress through stages of close apposition, hemifusion, and then the formation of small, and finally large, fusion pores. Clearly, highly divergent proteins have converged on the same overall strategy to mediate fusion, an essential step in the life cycle of every enveloped virus.",,"['White, Judith M.', 'Delos, Sue E.', 'Brecher, Matthew', 'Schornberg, Kathryn']",,,,
,PMC,Viral and Developmental Cell Fusion Mechanisms: Conservation and Divergence,http://dx.doi.org/10.1016/j.devcel.2007.12.008,PMC3549671,,,"Membrane fusion is a fundamental requirement in numerous developmental, physiological, and pathological processes in eukaryotes. So far, only a limited number of viral and cellular fusogens, proteins that fuse membranes, have been isolated and characterized. Despite the diversity in structures and functions of known fusogens, some common principles of action apply to all fusion reactions. These can serve as guidelines in the search for new fusogens, and may allow the formulation of a cross-species, unified theory to explain divergent and convergent evolutionary principles of membrane fusion.",,"['Sapir, Amir', 'Avinoam, Ori', 'Podbilewicz, Benjamin', 'Chernomordik, Leonid V.']",,,,
,PMC,PIN: A Novel Protein Involved in IFN-γ Accumulation of NOS-1 in Neurons,http://dx.doi.org/10.1089/dna.2007.0673,PMC2556631,,,"In this study we investigate the role of the protein inhibitor of NOS-1 (PIN) in the interferon-γ (IFN-γ)–mediated posttranscriptional accumulation of nitric oxide synthase-1 (NOS-1) and the anti-vesicular stomatitis virus response in neuronal cells. IFN-γ–induced enhancement of NOS-1 activity is crucial for its antiviral activity in the central nervous system. IFN-γ treatment of neuronal cells results in an increase of total NOS-1 and decrease of total PIN proteins without alteration in their respective mRNA levels. PIN/NOS-1 complexes decreased after IFN-γ treatment. Transfection of cells with small interfering RNA (siRNA) for PIN results in a higher constitutive activity of NOS-1 and inhibition of viral replication. IFN-γ treatment did not change the amount of NOS-1 detectable by Western blot, when PIN is diminished by RNAi treatment. Overexpression of PIN results in lower constitutive NOS-1 expression and activity, and diminishes activation of NOS-1 by IFN-γ. Our findings indicate that in neurons, IFN-γ upregulates NOS-1 through proteasomal degradation of PIN.",,"['Yang, Jingjun', 'Dennison, Natalie Nicole', 'Reiss, Carol Shoshkes']",,,,
,PMC,Axonal degeneration as a self-destructive defense mechanism against neurotropic virus infection,http://dx.doi.org/10.2217/17460794.3.6.579,PMC2600527,,,"Theiler's murine encephalomyelitis virus (TMEV) and other neurotropic virus infections result in degeneration of each component of the neuron: apoptosis of the cell body, axonal (Wallerian) degeneration, and dendritic and synaptic pathology. In general, axonal degeneration is detrimental for hosts. However, axonal degeneration can be beneficial in the case of infection with neurotropic viruses that spread in the CNS using axonal transport. C57BL/Wld(S) (Wld(S), Wallerian degeneration slow mutant) mice are protected from axonal degeneration. Wld(S) mice infected with the neurovirulent GDVII strain of TMEV are more resistant to virus infection than wild-type mice, suggesting that axonal preservation contributes to the resistance. By contrast, infection with the less virulent Daniels strain of TMEV results in high levels of virus propagation in the CNS, suggesting that prolonged survival of axons in Wld(S) mice favors virus spread. Thus, axonal degeneration might be a beneficial self-destruct mechanism that limits the spread of neurotropic viruses, in the case of less virulent virus infection. We hypothesize that neurons use ‘built-in’ self-destruct protection machinery (compartmental neurodegeneration) against neurotropic virus infection, since the CNS is an immunologically privileged site. Early induction of apoptosis in the neuronal cell body limits virus replication. Wallerian degeneration of the axon prevents axonal transport of virus. Dendritic and synaptic degeneration blocks virus transmission at synapses. Thus, the balance between neurodegeneration and virus propagation may be taken into account in the future design of neuroprotective therapy.",,"Tsunoda, Ikuo",,,,
,PMC,Resonant Cavity Imaging: A Means Toward High-Throughput Label-Free Protein Detection,http://dx.doi.org/10.1109/JSTQE.2007.913397,PMC2759719,,,"The resonant cavity imaging biosensor (RCIB) is an optical technique for detecting molecular binding interactions label free at many locations in parallel that employs an optical resonant cavity for high sensitivity. Near-infrared light centered at 1512.5 nm couples resonantly through a Fabry–Perot cavity constructed from dielectric reflectors (Si/SiO(2)), one of which serves as the binding surface. As the wavelength is swept using a tunable laser, a near-infrared digital camera monitors cavity transmittance at each pixel. A wavelength shift in the local resonant response of the optical cavity indicates binding. Positioning the sensing surface with respect to the standing wave pattern of the electric field within the cavity controls the sensitivity with which the presence of bound molecules is detected. Transmitted intensity at thousands of pixel locations is recorded simultaneously in a 10 s, 5 nm scan. An initial proof-of-principle setup has been constructed. A test sample was fabricated with 25, 100-μm wide square features, each with a different density of 1-μm square depressions etched 12 nm into the SiO(2) surface. The average depth of each etched region was found with 0.05 nm rms precision. In a second test, avidin, bound selectively to biotin conjugated bovine serum albumin, was detected.",,"['Bergstein, David A.', 'Özkumur, Emre', 'Wu, Arthur C.', 'Yalçin, Ayça', 'Colson, Jeremy R.', 'Needham, James W.', 'Irani, Rostem J.', 'Gershoni, Jonathan M.', 'Goldberg, Bennett B.', 'DeLisi, Charles', 'Ruane, Michael F.', 'Ünlü, M. Selim']",,,,
,PMC,In Vitro Antiviral Activity of some Novel Isatin Derivatives against HCV and SARS-CoV Viruses,http://dx.doi.org/10.4103/0250-474X.40339,PMC2852069,20390088,CC BY,"4-[(1,2-dihydro-2-oxo-3H-indol-3-ylidene)amino]-N(4,6-dimethyl-2-pyrimidiny)benzene sulphonamide and its derivatives were evaluated for antiviral activity against Pathogenic viruses such as Hepatitis C Virus and SARS-CoV in Vero and Huh 5-2 cells, respectively. The 5-fluoro derivative inhibited the HCV RNA synthesis at 6 μg/ml, without toxicity at a concentration up to 42 μg/ml in Huh 5-2 cells. Among the compounds tested SPIII-5F exhibits the 45% maximum protection against replication of SARS-CoV in Vero cells.",2008 Jan-Feb,"['Selvam, P.', 'Murgesh, N.', 'Chandramohan, M.', 'De Clercq, E.', 'Keyaerts, E.', 'Vijgen, L.', 'Maes, P.', 'Neyts, J.', 'Ranst, M. V.']",Indian J Pharm Sci,,,
,PMC,Baculovirus-infected insect cells expressing peptide-MHC complexes elicit protective antitumor immunity,,PMC3111388,,,"Evaluation of T cell responses to tumor- and pathogen-derived peptides in preclinical models is necessary to define the characteristics of efficacious peptide vaccines. We show here that vaccination with insect cells infected with baculoviruses expressing MHC class I linked to tumor peptide mimotopes results in expansion of functional peptide-specific CD8+ T cells that protect mice from tumor challenge. Specific peptide mimotopes selected from peptide-MHC libraries encoded by baculoviruses can be tested using this vaccine approach. Unlike other vaccine strategies, this vaccine has the following advantages: peptides that are difficult to solublize can be easily characterized, bona fide peptides without synthesis artifacts are presented, and additional adjuvants are not required to generate peptide-specific responses. Priming of antitumor responses occurs within three days of vaccination and is optimal one week after a second injection. After vaccination the antigen-specific T cell response is similar in animals primed with either soluble or membrane-bound antigen, and CD11c(+) dendritic cells increase expression of maturation markers and stimulate proliferation of specific T cells ex vivo. Thus, the mechanism of antigen presentation induced by this vaccine is consistent with cross-priming by dendritic cells. This straightforward approach will facilitate future analyses of T cells elicited by peptide mimotopes.",,"['Jordan, Kimberly R.', 'McMahan, Rachel H.', 'Oh, Jason Z.', 'Pipeling, Matthew R.', 'Pardoll, Drew M.', 'Kedl, Ross M.', 'Kappler, John W.', 'Slansky, Jill E.']",,,,
,PMC,Predicting linear B-cell epitopes using string kernels,http://dx.doi.org/10.1002/jmr.893,PMC2683948,,,"The identification and characterization of B-cell epitopes play an important role in vaccine design, immunodiagnostic tests, and antibody production. Therefore, computational tools for reliably predicting linear B-cell epitopes are highly desirable. We evaluated Support Vector Machine (SVM) classifiers trained utilizing five different kernel methods using fivefold cross-validation on a homology-reduced data set of 701 linear B-cell epitopes, extracted from Bcipep database, and 701 non-epitopes, randomly extracted from SwissProt sequences. Based on the results of our computational experiments, we propose BCPred, a novel method for predicting linear B-cell epitopes using the subsequence kernel. We show that the predictive performance of BCPred (AUC = 0.758) outperforms 11 SVM-based classifiers developed and evaluated in our experiments as well as our implementation of AAP (AUC = 0.7), a recently proposed method for predicting linear B-cell epitopes using amino acid pair antigenicity. Furthermore, we compared BCPred with AAP and ABCPred, a method that uses recurrent neural networks, using two data sets of unique B-cell epitopes that had been previously used to evaluate ABCPred. Analysis of the data sets used and the results of this comparison show that conclusions about the relative performance of different B-cell epitope prediction methods drawn on the basis of experiments using data sets of unique B-cell epitopes are likely to yield overly optimistic estimates of performance of evaluated methods. This argues for the use of carefully homology-reduced data sets in comparing B-cell epitope prediction methods to avoid misleading conclusions about how different methods compare to each other. Our homology-reduced data set and implementations of BCPred as well as the APP method are publicly available through our web-based server, BCPREDS, at: http://ailab.cs.iastate.edu/bcpreds/.",,"['EL-Manzalawy, Yasser', 'Dobbs, Drena', 'Honavar, Vasant']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.02463-07,PMC2224574,,,,,,,,,
,PMC,TUBERCULOUS SARCOIDOSIS: DOES IT EXIST?,http://dx.doi.org/10.4103/0970-2113.44140,PMC2853046,20396660,CC BY,,2008 Jan-Mar,"Dixit, Ramakant",Lung India,,,
,PMC,Emerging Viral Diseases,,PMC2496997,,,,,"['Pekosz, Andrew', 'Glass, Gregory E.']",,,,
,PMC,Morphogenesis of Coronavirus HCoV-NL63 in Cell Culture: A Transmission Electron Microscopic Study,http://dx.doi.org/10.2174/1874279300802010052,PMC2763395,,,"NL63 (HCoV-NL63) is a recently discovered human coronavirus that causes respiratory disease in infants and young children. NL63 productively infects LLCMK2 cells and ciliated epithelial cells of human airway cell cultures. Transmission electron microscopic (TEM) studies of NL63 infected LLCMK2 cells revealed that virions are spherical, spiked, and range from 75 to 115 nm in diameter. Virus replication predominantly occurs on the rough endoplasmic reticulum (RER), both perinuclear and cytoplasmic, and the Golgi. Plasma membrane budding was occasionally observed. As virus production increased, aberrant viral forms appeared with greater frequency. Unusual inclusions were present in infected cells including tubular and laminated structures. Pleomorphic double membrane-bound vesicles (DMV), measuring roughly 140 to 210 nm in diameter, were observed. The virus was released via exocytosis and cell lysis. In summary, we report the key morphologic characteristics of NL63 infection observed by TEM analysis.",,"['Orenstein, Jan M.', 'Banach, Bridget', 'Baker, Susan C.']",,,,
,PMC,Prevalence of Psychiatric Disorders Among Toronto Hospital Workers One to Two Years After the SARS Outbreak,http://dx.doi.org/10.1176/ps.2008.59.1.91,PMC2923654,,,"OBJECTIVE: This study aimed to determine the incidence of psychiatric disorders among health care workers in Toronto in the one- to two-year period after the 2003 outbreak of severe acute respiratory syndrome (SARS) and to test predicted risk factors. METHODS: New-onset episodes of psychiatric disorders were assessed among 139 health care workers by using the Structured Clinical Interview for DSM-IV and the Clinician-Administered PTSD Scale. Past history of psychiatric illness, years of health care experience, and the perception of adequate training and support were tested as predictors of the incidence of new-onset episodes psychiatric disorders after the SARS outbreak. RESULTS: The lifetime prevalence of any depressive, anxiety, or substance use diagnosis was 30%. Only one health care worker who identified the SARS experience as a traumatic event was diagnosed as having PTSD. New episodes of psychiatric disorders occurred among seven health care workers (5%). New episodes of psychiatric disorders were directly associated with a history of having a psychiatric disorder before the SARS outbreak (p=.02) and inversely associated with years of health care experience (p=.03) and the perceived adequacy of training and support (p=.03). CONCLUSIONS: Incidence of new episodes of psychiatric disorders after the SARS outbreak were similar to or lower than community incidence rates, which may indicate the resilience of health care workers who continued to work in hospitals one to two years after the SARS outbreak. In preparation for future events, such as pandemic influenza, training and support may bolster the resilience of health care workers who are at higher risk by virtue of their psychiatric history and fewer years of health care experience.",,"['Lancee, William J.', 'Maunder, Robert G.', 'Goldbloom, David S.', None]",,,,
,PMC,Professional Development for Prospective Epidemiology Teachers in Grades 6–12,,PMC2431095,,,,,"['Kaelin, Mark A.', 'Huebner, Wendy W.', 'Cordell, Ralph L.', 'Szklarczuk, Brian']",,,,
,PMC,Replicating Success: Developing a Standard FETP Curriculum,,PMC2233740,,,"Field epidemiology training programs have been successful models to address a country's needs for a skilled public health workforce, partly due to their responsiveness to the countries' unique needs. The Centers for Disease Control and Prevention has partnered with ministries of health to strengthen their workforce through customized competency-based training programs. While desirable, emphasis on program flexibility can result in redundancy and inconsistency. To address this challenge, the ADDIE model (analysis, design, development, implementation, and evaluation) of instructional design was used by a cross-functional team to guide completion of a standard curriculum based on 15 competencies. The standard curriculum has supported the development and expansion of programs while still allowing for adaptation. This article describes the process that was used to develop the curriculum, which, together with needs assessment and evaluation, is crucial for successful training programs.",,"['Traicoff, Denise A.', 'Walke, Henry T.', 'Jones, Donna S.', 'Gogstad, Eric K.', 'Imtiaz, Rubina', 'White, Mark E.']",,,,
,PMC,Safety of Upper-Room Ultraviolet Germicidal Air Disinfection for Room Occupants: Results from the Tuberculosis Ultraviolet Shelter Study,,PMC2099326,,,"OBJECTIVE: We evaluated the safety of room occupants in the Tuberculosis Ultraviolet Shelter Study (TUSS), a double-blind, placebo-controlled field trial of upper-room ultraviolet germicidal irradiation (UVGI) at 14 homeless shelters in six U.S. cities from 1997 to 2004. METHODS: Data collection involved administering questionnaires regarding eye and skin irritation to a total of 3,611 staff and homeless study subjects. RESULTS: Among these subjects, there were 223 reports of eye or skin symptoms. During the active UV period, 95 questionnaires (6%) noted such symptoms, and during the placebo period, 92 questionnaires (6%) did so. In the 36 remaining cases, either the UV period when symptoms took place was unknown or the symptoms spanned both periods. There was no statistically significant difference in the number of reports of symptoms between the active and placebo periods. One definite instance of UV-related keratoconjunctivitis occurred, resulting from a placement of a bunk bed in a dormitory where a single bed had been used when the UV fixtures were first installed. CONCLUSION: These findings demonstrate that careful application of upper-room UVGI can be achieved without an apparent increase in the incidence of the most common side effects of accidental UV overexposure.",,"['Nardell, Edward A.', 'Bucher, Scott J.', 'Brickner, Philip W.', 'Wang, Charles', 'Vincent, Richard L.', 'Becan-McBride, Kathleen', 'James, Mark A.', 'Michael, Max', 'Wright, James D.']",,,,
,PMC,Ethical Obligations of Physicians Participating in Public Health Quarantine and Isolation Measures,,PMC2099320,,,"In dealing with outbreaks of communicable diseases, the medical profession should work with public health authorities to promote the use of interventions that achieve desired public health outcomes with minimal infringement upon individual liberties. This article endeavors to help physicians manage their dual responsibilities to their patients and to their communities when participating in appropriate quarantine and isolation measures. In implementing such measures, individual physicians should take necessary actions to promote patients' well-being. In addition, the medical profession and individual physicians share responsibility for taking appropriate precautionary measures to protect the health of individuals caring for patients with communicable diseases.",,"['Bostick, Nathan A.', 'Levine, Mark A.', 'Sade, Robert M.']",,,,
,PMC,President's Address: Travel Medicine and Principles of Safe Travel,,PMC2394696,,,"Persons crossing international boundaries away from their medical support systems are put at risk for illness and injury. Travel medicine is a new medical discipline that quantifies these health risks and develops strategies for reducing them. Obtaining health and evacuation insurance for a future trip is important for persons with medical conditions, those planning trips to developing tropical or semi-tropical regions of the world or when an international stay anywhere will be as long as a month. Pre-travel medical evaluation, vaccines against endemic infectious diseases and medications to reduce the occurrence of diarrhea and malaria during trips to endemic areas, and medications for self-treatment of common illnesses such as diarrhea are fundamental to travel medicine. There are a number of miscellaneous areas to consider in travel medicine including preventing deep vein thrombosis and minimizing jet lag during long haul air travel and reducing the occurrence of accidents and water- and altitude-related illnesses. An important recently defined challenge to the field is the growing number of ill-prepared persons put at great risk for illness while visiting friends and relatives living in areas of reduced hygiene. All persons need to have an idea of how and where they may find medical care if they develop illness while abroad. This article summarizes essential elements in travel medicine and offers 10 recommendations for safe travel.",,"DuPont, Herbert L.",,,,
,PMC,Preparation of Armored RNA as a Control for Multiplex Real-Time Reverse Transcription-PCR Detection of Influenza Virus and Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JCM.01904-07,PMC2268373,,,"The common respiratory viruses, including influenza A, influenza B, and newly emerging severe acute respiratory syndrome (SARS) viruses, may cause similar clinical symptoms. Therefore, differential diagnosis of these virus pathogens is frequently required for single clinical samples. In addition, there is an urgent need for noninfectious and stable RNA standards and controls for multivirus detection. In this study, reverse transcription-PCR (RT-PCR) targeting of the RNAs of influenza A and influenza B viruses and SARS coronavirus was performed, and the resulting products were spliced into a fragment which was packaged into armored RNA for use as a noninfectious, quantifiable synthetic substitute. Furthermore, in the present study we developed a multiplex real-time RT-PCR assay in which the armored RNA was used as an external positive control and the three RNA viruses could be detected simultaneously in a single reaction mix. The detection limit of the multiplex real-time PCR was 10 copies/μl of armored RNA.",,"['Yu, Xin-Fen', 'Pan, Jing-Cao', 'Ye, Rong', 'Xiang, Hai-Qing', 'Kou, Yu', 'Huang, Zhi-Cheng']",,,,
,PMC,Chimeric coronavirus-like particles carrying severe acute respiratory syndrome coronavirus (SCoV) S protein protects mice against challenge with SCoV,http://dx.doi.org/10.1016/j.vaccine.2007.11.092,PMC2267761,,,"We tested the efficacy of coronavirus-like particles (VLPs) for protecting mice against severe acute respiratory syndrome coronavirus (SCoV) infection. Coexpression of SCoV S protein and E, M and N proteins of mouse hepatitis virus in 293T or CHO cells resulted in the efficient production of chimeric VLPs carrying SCoV S protein. Balb/c mice inoculated with a mixture of chimeric VLPs and alum twice at an interval of four weeks were protected from SCoV challenge, as indicated by the absence of infectious virus in the lungs. The same groups of mice had high levels of SCoV-specific neutralizing antibodies, while mice in the negative control groups, which were not immunized with chimeric VLPs, failed to manifest neutralizing antibodies, suggesting that SCoV-specific neutralizing antibodies are important for the suppression of viral replication within the lungs. Despite some differences in the cellular composition of inflammatory infiltrates, we did not observe any overt lung pathology in the chimeric-VLP-treated mice, when compared to the negative control mice. Our results show that chimeric VLP can be an effective vaccine strategy against SCoV infection.",,"['Lokugamage, Kumari G.', 'Yoshikawa-Iwata, Naoko', 'Ito, Naoto', 'Watts, Douglas M.', 'Wyde, Philip R.', 'Wang, Nan', 'Newman, Patrick', 'Tseng, Chien-Te Kent', 'Peters, C. J.', 'Makino, Shinji']",,,,
,PMC,Visiting times,http://dx.doi.org/10.1136/bmj.39420.392373.BE,PMC2151159,,,Sadia Ismail and Graham Mulley discuss the evolution of rules surrounding visiting patients in hospital,,"['Ismail, Sadia', 'Mulley, Graham']",,,,
,PMC,Results From a Hypothesis Generating Case-Control Study: Herpes Family Viruses and Schizophrenia Among Military Personnel,http://dx.doi.org/10.1093/schbul/sbm139,PMC2632504,,,"Background: Herpes family viruses can cause central nervous system inflammatory changes that can present with symptoms indistinguishable from schizophrenia and therefore are of interest in schizophrenia research. Most existing studies of herpes viruses have used small populations and postdiagnosis specimens. As part of a larger research program, we conducted a hypothesis-generating case-control study of selected herpes virus antibodies among individuals discharged from the US military with schizophrenia and pre- and postdiagnosis sera. Methods: Cases (n = 180) were servicemembers hospitalized and discharged from military service with schizophrenia. Controls, 3:1 matched on several factors, were members not discharged. The military routinely collects and stores members' serum specimens. We used microplate enzyme immunoassay to measure immunoglobulin G (IgG) antibody levels to 6 herpes viruses in pre- and postdiagnosis specimens. Conditional logistic regression was used, and the measure of association was the hazard ratio (HR). Results: Overall, we found a significant association between human herpes virus type 6 and schizophrenia, with an HR of 1.17 (95% confidence interval [CI] = 1.04, 1.32). Women and blacks had significant negative associations with herpes simplex virus type 2 and cytomegalovirus; among blacks, there was a significant positive association with herpes simplex virus type 1. Among men, there was a HHV-6 temporal effect with an HR of 1.41 (95% CI = 1.02, 1.96) for sera drawn 6–12 months before diagnosis. Discussion: Findings from previous studies of herpes family viruses and schizophrenia have been inconsistent. Our study is based on a larger population than most previous studies and used serum specimens collected before onset of illness. This study adds to the body of knowledge and provides testable hypotheses for follow-on studies.",,"['Niebuhr, David W.', 'Millikan, Amy M.', 'Yolken, Robert', 'Li, Yuanzhang', 'Weber, Natalya S.']",,,,
,PMC,The 1918–1919 influenza pandemic in England and Wales: spatial patterns in transmissibility and mortality impact,http://dx.doi.org/10.1098/rspb.2007.1477,PMC2596813,,,"Spatial variations in disease patterns of the 1918–1919 influenza pandemic remain poorly studied. We explored the association between influenza death rates, transmissibility and several geographical and demographic indicators for the autumn and winter waves of the 1918–1919 pandemic in cities, towns and rural areas of England and Wales. Average measures of transmissibility, estimated by the reproduction number, ranged between 1.3 and 1.9, depending on model assumptions and pandemic wave and showed little spatial variation. Death rates varied markedly with urbanization, with 30–40% higher rates in cities and towns compared with rural areas. In addition, death rates varied with population size across rural settings, where low population areas fared worse. By contrast, we found no association between transmissibility, death rates and indicators of population density and residential crowding. Further studies of the geographical mortality patterns associated with the 1918–1919 influenza pandemic may be useful for pandemic planning.",,"['Chowell, Gerardo', 'Bettencourt, Luís M.A', 'Johnson, Niall', 'Alonso, Wladimir J', 'Viboud, Cécile']",,,,
,PMC,Evidence for Differential Roles for NKG2D Receptor Signaling in Innate Host Defense against Coronavirus-Induced Neurological and Liver Disease,http://dx.doi.org/10.1128/JVI.02032-07,PMC2259007,,,"Infection of SCID mice with a recombinant murine coronavirus (mouse hepatitis virus [MHV]) expressing the T-cell chemoattractant CXC chemokine ligand 10 (CXCL10) resulted in increased survival and reduced viral burden within the brain and liver compared to those of mice infected with an isogenic control virus (MHV), supporting an important role for CXCL10 in innate immune responses following viral infection. Enhanced protection in MHV-CXCL10-infected mice correlated with increased gamma interferon (IFN-γ) production by infiltrating natural killer (NK) cells within the brain and reduced liver pathology. To explore the underlying mechanisms associated with protection from disease in MHV-CXCL10-infected mice, the functional contributions of the NK cell-activating receptor NKG2D in host defense were examined. The administration of an NKG2D-blocking antibody to MHV-CXCL10-infected mice did not reduce survival, dampen IFN-γ production in the brain, or affect liver pathology. However, NKG2D neutralization increased viral titers within the liver, suggesting a protective role for NKG2D signaling in this organ. These data indicate that (i) CXCL10 enhances innate immune responses, resulting in protection from MHV-induced neurological and liver disease; (ii) elevated NK cell IFN-γ expression in the brain of MHV-CXCL10-infected mice occurs independently of NKG2D; and (iii) NKG2D signaling promotes antiviral activity within the livers of MHV-infected mice that is not dependent on IFN-γ and tumor necrosis factor alpha secretion.",,"['Walsh, Kevin B.', 'Lodoen, Melissa B.', 'Edwards, Robert A.', 'Lanier, Lewis L.', 'Lane, Thomas E.']",,,,
,PMC,The Spike Protein of Infectious Bronchitis Virus Is Retained Intracellularly by a Tyrosine Motif,http://dx.doi.org/10.1128/JVI.02064-07,PMC2258963,,,"We have analyzed the intracellular transport of the spike (S) protein of infectious bronchitis virus (IBV), an avian coronavirus. Surface expression was analyzed by immunofluorescence microscopy, by surface biotinylation, and by syncytium formation by S-expressing cells. By applying these methods, the S protein was found to be retained intracellularly. Tyr1143 in the cytoplasmic tail was shown to be a crucial component of the retention signal. Deletion of a dilysine motif that has previously been suggested to function as a retrieval signal did not abolish intracellular retention. Treatment of the S proteins with endoglycosidases did not reveal any differences between the parental and the mutant proteins. Furthermore, all S proteins analyzed were posttranslationally cleaved into the subunits S1 and S2. In coexpression experiments, the S protein was found to colocalize with a Golgi marker. Taken together, these results indicate that the S protein of IBV is retained at a late Golgi compartment. Therefore, this viral surface protein differs from the S proteins of transmissible gastroenteritis virus and severe acute respiratory syndrome coronavirus, which are retained at a pre-Golgi compartment or transported to the cell surface, respectively. The implications of these differences are discussed.",,"['Winter, Christine', 'Schwegmann-Wessels, Christel', 'Neumann, Ulrich', 'Herrler, Georg']",,,,
,PMC,Antibody-Dependent Enhancement of Hepatitis C Virus Infection,http://dx.doi.org/10.1128/JVI.01867-07,PMC2258956,,,"Hepatitis C virus (HCV) often causes a persistent infection associated with hypergammaglobulinemia, high levels of antiviral antibody and circulating immune complexes, and immune complex disease. We previously reported that only a limited neutralizing activity to vesicular stomatitis virus or HCV pseudotype is generated in animals immunized with recombinant HCV envelope proteins and chronically infected HCV patient sera. Interestingly, when some of these neutralizing sera were diluted into a range of concentrations below those that reduced virus plaque number, an increase in pseudotype plaque formation was observed. Purified HCV E2-specific human monoclonal antibodies were used to further verify the specificity of this enhancement, and one- to twofold increases were apparent on permissive Huh-7 cells. The enhancement of HCV pseudotype titer could be inhibited by the addition of a Fc-specific anti-human immunoglobulin G Fab fragment to the virus-antibody mixture prior to infection. Treatment of cells with antibody to Fc receptor I (FcRI) or FcRII, but not FcRIII, also led to an inhibition of pseudotype titer enhancement in an additive manner. Human lymphoblastoid cell line (Raji), a poor host for HCV pseudotype infection, exhibited a four- to sixfold enhancement of pseudotype-mediated cell death upon incubation with antibody at nonneutralizing concentrations. A similar enhancement of cell culture-grown HCV infectivity by a human monoclonal antibody was also observed. Taken together, antibodies to viral epitopes enhancing HCV infection need to be taken into consideration for pathogenesis and in the development of an effective vaccine.",,"['Meyer, Keith', 'Ait-Goughoulte, Malika', 'Keck, Zhen-Yong', 'Foung, Steven', 'Ray, Ranjit']",,,,
,PMC,Visualization of Double-Stranded RNA in Cells Supporting Hepatitis C Virus RNA Replication,http://dx.doi.org/10.1128/JVI.01565-07,PMC2258944,,,"The mechanisms involved in hepatitis C virus (HCV) RNA replication are unknown, and this aspect of the virus life cycle is not understood. It is thought that virus-encoded nonstructural proteins and RNA genomes interact on rearranged endoplasmic reticulum (ER) membranes to form replication complexes, which are believed to be sites of RNA synthesis. We report that, through the use of an antibody specific for double-stranded RNA (dsRNA), dsRNA is readily detectable in Huh-7 cells that contain replicating HCV JFH-1 genomes but is absent in control cells. Therefore, as that of other RNA virus genomes, the replication of the HCV genome may involve the generation of a dsRNA replicative intermediate. In Huh-7 cells supporting HCV RNA replication, dsRNA was observed as discrete foci, associated with virus-encoded NS5A and core proteins and identical in morphology and distribution to structures containing HCV RNA visualized by fluorescence-based hybridization methods. Three-dimensional reconstruction of deconvolved z-stack images of virus-infected cells provided detailed insight into the relationship among dsRNA foci, NS5A, the ER, and lipid droplets (LDs). This analysis revealed that dsRNA foci were located on the surface of the ER and often surrounded, partially or wholly, by a network of ER-bound NS5A protein. Additionally, virus-induced dsRNA foci were juxtaposed to LDs, attached to the ER. Thus, we report the visualization of HCV-induced dsRNA foci, the likely sites of virus RNA replication, and propose that HCV genome synthesis occurs at LD-associated sites attached to the ER in virus-infected cells.",,"['Targett-Adams, Paul', 'Boulant, Steeve', 'McLauchlan, John']",,,,
,PMC,Mechanisms of Zoonotic Severe Acute Respiratory Syndrome Coronavirus Host Range Expansion in Human Airway Epithelium,http://dx.doi.org/10.1128/JVI.02041-07,PMC2258931,,,"In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) emerged and caused over 8,000 human cases of infection and more than 700 deaths worldwide. Zoonotic SARS-CoV likely evolved to infect humans by a series of transmission events between humans and animals for sale in China. Using synthetic biology, we engineered the spike protein (S) from a civet strain, SZ16, into our epidemic strain infectious clone, creating the chimeric virus icSZ16-S, which was infectious but yielded progeny viruses incapable of propagating in vitro. After introducing a K479N mutation within the S receptor binding domain (RBD) of SZ16, the recombinant virus (icSZ16-S K479N) replicated in Vero cells but was severely debilitated in growth. The in vitro evolution of icSZ16-S K479N on human airway epithelial (HAE) cells produced two viruses (icSZ16-S K479N D8 and D22) with enhanced growth on HAE cells and on delayed brain tumor cells expressing the SARS-CoV receptor, human angiotensin I converting enzyme 2 (hACE2). The icSZ16-S K479N D8 and D22 virus RBDs contained mutations in ACE2 contact residues, Y442F and L472F, that remodeled S interactions with hACE2. Further, these viruses were neutralized by a human monoclonal antibody (MAb), S230.15, but the parent icSZ16-S K479N strain was eight times more resistant than the mutants. These data suggest that the human adaptation of zoonotic SARS-CoV strains may select for some variants that are highly susceptible to select MAbs that bind to RBDs. The epidemic, icSZ16-S K479N, and icSZ16-S K479N D22 viruses replicate similarly in the BALB/c mouse lung, highlighting the potential use of these zoonotic spike SARS-CoVs to assess vaccine or serotherapy efficacy in vivo.",,"['Sheahan, Timothy', 'Rockx, Barry', 'Donaldson, Eric', 'Sims, Amy', 'Pickles, Raymond', 'Corti, Davide', 'Baric, Ralph']",,,,
,PMC,Jaagsiekte Sheep Retrovirus Utilizes a pH-Dependent Endocytosis Pathway for Entry,http://dx.doi.org/10.1128/JVI.01853-07,PMC2258929,,,"Using Moloney murine leukemia virus pseudovirions bearing the envelope protein of Jaagsiekte sheep retrovirus (JSRV), we report here that entry was weakly inhibited by lysosomotropic agents but was profoundly blocked by bafilomycin A1 (BafA1). Kinetics studies revealed that JSRV entry is a slow process and was substantially blocked by a dominant-negative mutant of dynamin. Interestingly, a low-pH pulse overcame the BafA1 block to JSRV infection, although this occurred only if virus-bound cells were preincubated at 37°C, consistent with a very early entry event such as endocytosis being required before the low-pH-dependent step occurs. Moreover, JSRV pseudovirions were resistant to low-pH inactivation. Altogether, this study reveals that JSRV utilizes a pH-dependent, dynamin-associated endocytosis pathway for entry that differs from the classical pH-dependent entry pathway of vesicular stomatitis virus.",,"['Bertrand, Pascale', 'Côté, Marceline', 'Zheng, Yi-Min', 'Albritton, Lorraine M.', 'Liu, Shan-Lu']",,,,
,PMC,Structures of Two Coronavirus Main Proteases: Implications for Substrate Binding and Antiviral Drug Design,http://dx.doi.org/10.1128/JVI.02114-07,PMC2258912,,,"Coronaviruses (CoVs) can infect humans and multiple species of animals, causing a wide spectrum of diseases. The coronavirus main protease (M(pro)), which plays a pivotal role in viral gene expression and replication through the proteolytic processing of replicase polyproteins, is an attractive target for anti-CoV drug design. In this study, the crystal structures of infectious bronchitis virus (IBV) M(pro) and a severe acute respiratory syndrome CoV (SARS-CoV) M(pro) mutant (H41A), in complex with an N-terminal autocleavage substrate, were individually determined to elucidate the structural flexibility and substrate binding of M(pro). A monomeric form of IBV M(pro) was identified for the first time in CoV M(pro) structures. A comparison of these two structures to other available M(pro) structures provides new insights for the design of substrate-based inhibitors targeting CoV M(pro)s. Furthermore, a Michael acceptor inhibitor (named N3) was cocrystallized with IBV M(pro) and was found to demonstrate in vitro inactivation of IBV M(pro) and potent antiviral activity against IBV in chicken embryos. This provides a feasible animal model for designing wide-spectrum inhibitors against CoV-associated diseases. The structure-based optimization of N3 has yielded two more efficacious lead compounds, N27 and H16, with potent inhibition against SARS-CoV M(pro).",,"['Xue, Xiaoyu', 'Yu, Hongwei', 'Yang, Haitao', 'Xue, Fei', 'Wu, Zhixin', 'Shen, Wei', 'Li, Jun', 'Zhou, Zhe', 'Ding, Yi', 'Zhao, Qi', 'Zhang, Xuejun C.', 'Liao, Ming', 'Bartlam, Mark', 'Rao, Zihe']",,,,
,PMC,CD4 T Cells Contribute to Virus Control and Pathology following Central Nervous System Infection with Neurotropic Mouse Hepatitis Virus,http://dx.doi.org/10.1128/JVI.01762-07,PMC2258904,,,"Replication of the neurotropic mouse hepatitis virus strain JHM (JHMV) is controlled primarily by CD8(+) T-cell effectors utilizing gamma interferon (IFN-γ) and perforin-mediated cytotoxicity. CD4(+) T cells provide an auxiliary function(s) for CD8(+) T-cell survival; however, their direct contribution to control of virus replication and pathology is unclear. To examine a direct role of CD4(+) T cells in viral clearance and pathology, pathogenesis was compared in mice deficient in both perforin and IFN-γ that were selectively reconstituted for these functions via transfer of virus-specific memory CD4(+) T cells. CD4(+) T cells from immunized wild-type, perforin-deficient, and IFN-γ-deficient donors all initially reduced virus replication. However, prolonged viral control by IFN-γ-competent donors suggested that IFN-γ is important for sustained virus control. Local release of IFN-γ was evident by up-regulation of class II molecules on microglia in recipients of IFN-γ producing CD4(+) T cells. CD4(+) T-cell-mediated antiviral activity correlated with diminished clinical symptoms, pathology, and demyelination. Both wild-type donor CD90.1 and recipient CD90.2 CD4(+) T cells trafficked into the central nervous system (CNS) parenchyma and localized to infected white matter, correlating with decreased numbers of virus-infected oligodendrocytes in the CNS. These data support a direct, if limited, antiviral role for CD4(+) T cells early during acute JHMV encephalomyelitis. Although the antiviral effector mechanism is initially independent of IFN-γ secretion, sustained control of CNS virus replication by CD4(+) T cells requires IFN-γ.",,"['Stohlman, Stephen A.', 'Hinton, David R.', 'Parra, Beatriz', 'Atkinson, Roscoe', 'Bergmann, Cornelia C.']",,,,
,PMC,Assessment of antibody responses against gp41 in HIV-1-infected patients using soluble gp41 fusion proteins and peptides derived from M group consensus envelope,http://dx.doi.org/10.1016/j.virol.2007.11.009,PMC2293309,,,"Human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 is targeted by broadly-reactive neutralizing antibodies 2F5 and 4E10, making it an attractive target for vaccine development. To better assess immunogenic properties of gp41, we generated five soluble glutathione S-transferase fusion proteins encompassing C-terminal 30, 64, 100, 142, or 172 (full-length) amino acids of gp41 ectodomain from M group consensus envelope sequence. Antibody responses in HIV-1-infected patients were evaluated using these proteins and overlapping peptides. We found (i) antibody responses against different regions of gp41 varied tremendously among individual patients, (ii) patients with stronger antibody responses against membrane-proximal external region exhibit broader and more potent neutralizing activity, and (iii) several patients mounted antibodies against epitopes that are near, or overlap with, those targeted by 2F5 or 4E10. These soluble gp41 fusion proteins could be an important source of antigens for future vaccine development efforts.",,"['Penn-Nicholson, Adam', 'Han, Dong P.', 'Kim, Soon J.', 'Park, Hanna', 'Ansari, Rais', 'Montefiori, David C.', 'Cho, Michael W.']",,,,
,PMC,Steps to a leaner Europe,http://dx.doi.org/10.1136/bmj.39423.452106.AD,PMC2137086,,,Obesity is a growing public health problem. Rory Watson reports on European initiatives to tackle it and wider health problems,,"Watson, Rory",,,,
,PMC,Ovarian Tumor (OTU)-domain Containing Viral Proteases Evade Ubiquitin- and ISG15-dependent Innate Immune Responses,http://dx.doi.org/10.1016/j.chom.2007.09.014,PMC2184509,,,"Ubiquitin (Ub) and interferon stimulated gene product 15 (ISG15) reversibly conjugate to proteins via a conserved LRLRGG C-terminal motif, mediating important innate antiviral responses. The ovarian tumor (OTU) domain represents a superfamily of predicted proteases found in eukaryotic, bacterial and viral proteins, some of which have Ub-deconjugating activity. We show that the OTU domain-containing proteases of nairoviruses and arteriviruses hydrolyze Ub and ISG15 from cellular target proteins. This broad activity contrasts with the target specificity of known mammalian OTU domain-containing proteins. The biological significance of this activity of viral OTU domain-containing proteases was evidenced by their capacity to inhibit NF-κB dependent signaling and to antagonize the antiviral effects of ISG15 during Sindbis virus infection in vivo. The deconjugating activity of viral OTU proteases represents a novel viral immune evasion mechanism that inhibits Ub-and ISG15-dependent antiviral pathways.",,"['Frias-Staheli, Natalia', 'Giannakopoulos, Nadia V.', 'Kikkert, Marjolein', 'Taylor, Shannon L.', 'Bridgen, Anne', 'Paragas, Jason J.', 'Richt, Juergen A.', 'Rowland, Raymond R.', 'Schmaljohn, Connie S.', 'Lenschow, Deborah J.', 'Snijder, Eric J.', 'García-Sastre, Adolfo', 'Virgin, Herbert Whiting']",,,,
,PMC,"Human Parechovirus Type 1, 3, 4, 5, and 6 Detection in Picornavirus Cultures",http://dx.doi.org/10.1128/JCM.02009-07,PMC2238116,,,"Picornavirus cultures that could not be typed in neutralization assays were analyzed by VP1 reverse transcription-PCR (RT-PCR) and a virus discovery tool (VIDISCA). Human parechoviruses (HPeVs) were frequently identified, among which were the uncommon isolates HPeV-4, HPeV-5, and HPeV-6. The HPeV-5 isolate could be amplified only by VIDISCA and not by VP1 RT-PCR.",,"['de Vries, Michel', 'Pyrc, Krzysztof', 'Berkhout, Ron', 'Vermeulen-Oost, Wilma', 'Dijkman, Ronald', 'Jebbink, Maarten F.', 'Bruisten, Sylvia', 'Berkhout, Ben', 'van der Hoek, Lia']",,,,
,PMC,Hepatitis C Virus Genotype 1a Growth and Induction of Autophagy,http://dx.doi.org/10.1128/JVI.02093-07,PMC2258951,,,"We have previously reported that immortalized human hepatocytes (IHH) support the generation of infectious hepatitis C virus (HCV) genotype 1a (clone H77). In the present study, we have investigated the growth of HCV genotype 1a (clone H77) through serial passages and accompanying changes in IHH in response to infection. Eleven serial passages of HCV genotype 1a (clone H77) in IHH were completed. Virus replication was ascertained from the presence of HCV-specific sequences, the detection of core antigen, the virus genome copy number, and the virus titer in IHH culture fluid. Electron microscopy suggested that HCV infection induces autophagic vacuole formation in IHH. Fluorescence microscopy displayed localization of autophagic markers, microtubule-associated protein-1 light chain-3 and Apg5, on the vacuoles of HCV-infected hepatocytes. Taken together, our results suggested that HCV genotype 1a (clone H77) can be serially passaged in IHH and that HCV infection induces an autophagic response in hepatocytes.",,"['Ait-Goughoulte, Malika', 'Kanda, Tatsuo', 'Meyer, Keith', 'Ryerse, Jan S.', 'Ray, Ratna B.', 'Ray, Ranjit']",,,,
,PMC,Coronavirus Escape from Heptad Repeat 2 (HR2)-Derived Peptide Entry Inhibition as a Result of Mutations in the HR1 Domain of the Spike Fusion Protein,http://dx.doi.org/10.1128/JVI.02287-07,PMC2258948,,,"Peptides based on heptad repeat (HR) domains of class I viral fusion proteins are considered promising antiviral drugs targeting virus cell entry. We have analyzed the evolution of the mouse hepatitis coronavirus during multiple passaging in the presence of an HR2-based fusion inhibitor. Drug-resistant variants emerged as a result of multiple substitutions in the spike fusion protein, notably within a 19-residue segment of the HR1 region. Strikingly, one mutation, an A1006V substitution, which consistently appeared first in four independently passaged viruses, was the main determinant of the resistance phenotype, suggesting that only limited options exist for escape from the inhibitory effect of the HR2 peptide.",,"['Bosch, Berend Jan', 'Rossen, John W. A.', 'Bartelink, Willem', 'Zuurveen, Stephanie J.', 'de Haan, Cornelis A. M.', 'Duquerroy, Stephane', 'Boucher, Charles A. B.', 'Rottier, Peter J. M.']",,,,
,PMC,Genome Organization and Reverse Genetic Analysis of a Type I Feline Coronavirus,http://dx.doi.org/10.1128/JVI.02339-07,PMC2258703,,,"In this study we report the complete sequence and genome organization of the serotype I feline coronavirus (FCoV) strain Black. Furthermore, a reverse genetic system was established for this FCoV strain by cloning a full-length cDNA copy into vaccinia virus. This clone served as basis for the generation of recombinant FCoV (recFCoV) that was shown to bear the same features in vitro as the parental FCoV. Using this system, accessory 3abc genes in the FCoV genome were replaced by green fluorescent protein (recFCoV-GFP) and Renilla luciferase genes (recFCoV-RL). In addition, we showed that feline CD14(+) blood monocytes and dendritic cells can be easily detected after infection with recFCoV-GFP. Thus, our established reverse genetic system provides a suitable tool to study the molecular biology of serotype I FCoV.",,"['Tekes, Gergely', 'Hofmann-Lehmann, Regina', 'Stallkamp, Iris', 'Thiel, Volker', 'Thiel, Heinz-Jürgen']",,,,
,PMC,Difference in Receptor Usage between Severe Acute Respiratory Syndrome (SARS) Coronavirus and SARS-Like Coronavirus of Bat Origin,http://dx.doi.org/10.1128/JVI.01085-07,PMC2258702,,,"Severe acute respiratory syndrome (SARS) is caused by the SARS-associated coronavirus (SARS-CoV), which uses angiotensin-converting enzyme 2 (ACE2) as its receptor for cell entry. A group of SARS-like CoVs (SL-CoVs) has been identified in horseshoe bats. SL-CoVs and SARS-CoVs share identical genome organizations and high sequence identities, with the main exception of the N terminus of the spike protein (S), known to be responsible for receptor binding in CoVs. In this study, we investigated the receptor usage of the SL-CoV S by combining a human immunodeficiency virus-based pseudovirus system with cell lines expressing the ACE2 molecules of human, civet, or horseshoe bat. In addition to full-length S of SL-CoV and SARS-CoV, a series of S chimeras was constructed by inserting different sequences of the SARS-CoV S into the SL-CoV S backbone. Several important observations were made from this study. First, the SL-CoV S was unable to use any of the three ACE2 molecules as its receptor. Second, the SARS-CoV S failed to enter cells expressing the bat ACE2. Third, the chimeric S covering the previously defined receptor-binding domain gained its ability to enter cells via human ACE2, albeit with different efficiencies for different constructs. Fourth, a minimal insert region (amino acids 310 to 518) was found to be sufficient to convert the SL-CoV S from non-ACE2 binding to human ACE2 binding, indicating that the SL-CoV S is largely compatible with SARS-CoV S protein both in structure and in function. The significance of these findings in relation to virus origin, virus recombination, and host switching is discussed.",,"['Ren, Wuze', 'Qu, Xiuxia', 'Li, Wendong', 'Han, Zhenggang', 'Yu, Meng', 'Zhou, Peng', 'Zhang, Shu-Yi', 'Wang, Lin-Fa', 'Deng, Hongkui', 'Shi, Zhengli']",,,,
,PMC,Replicating and Non-replicating Viral Vectors for Vaccine Development,http://dx.doi.org/10.1016/j.copbio.2007.10.010,PMC2245896,,,,,"Robert-Guroff, Marjorie",,,,
,PMC,Binding of Dr adhesins of Escherichia coli to carcinoembryonic antigen triggers receptor dissociation,http://dx.doi.org/10.1111/j.1365-2958.2007.06054.x,PMC2628979,,,"Carcinoembryonic antigen (CEA) related cell adhesion molecules (CEACAMs) are host receptors for the Dr family of adhesins of Escherichia coli. To define the mechanism for binding of Dr adhesins to CEACAM receptors, we carried out structural studies on the N-terminal domain of CEA and its complex with the Dr adhesin. The crystal structure of CEA reveals a dimer similar to other dimers formed by receptors with IgV-like domains. The structure of the CEA/Dr adhesin complex is proposed based on NMR spectroscopy and mutagenesis data in combination with biochemical characterization. The Dr adhesin/CEA interface overlaps appreciably with the region responsible for CEA dimerization. Binding kinetics, mutational analysis, and spectroscopic examination of CEA dimers suggest that Dr adhesins can dissociate CEA dimers prior to the binding of monomeric forms. Our conclusions include a plausible mechanism for how E. coli, and perhaps other bacterial and viral pathogens, exploit CEACAMs. The present structure of the complex provides a powerful tool for the design of novel inhibitory strategies to treat E. coli infections.",,"['Korotkova, Natalia', 'Yang, Yi', 'Le Trong, Isolde', 'Cota, Ernesto', 'Demeler, Borries', 'Marchant, Jan', 'Thomas, Wendy E.', 'Stenkamp, Ronald E.', 'Moseley, Steve L.', 'Matthews, Steve']",,,,
,PMC,Estimation of multiple transmission rates for epidemics in heterogeneous populations,http://dx.doi.org/10.1073/pnas.0706461104,PMC2154441,,,"One of the principal challenges in epidemiological modeling is to parameterize models with realistic estimates for transmission rates in order to analyze strategies for control and to predict disease outcomes. Using a combination of replicated experiments, Bayesian statistical inference, and stochastic modeling, we introduce and illustrate a strategy to estimate transmission parameters for the spread of infection through a two-phase mosaic, comprising favorable and unfavorable hosts. We focus on epidemics with local dispersal and formulate a spatially explicit, stochastic set of transition probabilities using a percolation paradigm for a susceptible–infected (S–I) epidemiological model. The S–I percolation model is further generalized to allow for multiple sources of infection including external inoculum and host-to-host infection. We fit the model using Bayesian inference and Markov chain Monte Carlo simulation to successive snapshots of damping-off disease spreading through replicated plant populations that differ in relative proportions of favorable and unfavorable hosts and with time-varying rates of transmission. Epidemiologically plausible parametric forms for these transmission rates are compared by using the deviance information criterion. Our results show that there are four transmission rates for a two-phase system, corresponding to each combination of infected donor and susceptible recipient. Knowing the number and magnitudes of the transmission rates allows the dominant pathways for transmission in a heterogeneous population to be identified. Finally, we show how failure to allow for multiple transmission rates can overestimate or underestimate the rate of spread of epidemics in heterogeneous environments, which could lead to marked failure or inefficiency of control strategies.",,"['Cook, Alex R.', 'Otten, Wilfred', 'Marion, Glenn', 'Gibson, Gavin J.', 'Gilligan, Christopher A.']",,,,
,PMC,Equine Infectious Anemia Virus Entry Occurs through Clathrin-Mediated Endocytosis,http://dx.doi.org/10.1128/JVI.01754-07,PMC2258727,,,"Entry of wild-type lentivirus equine infectious anemia virus (EIAV) into cells requires a low-pH step. This low-pH constraint implicates endocytosis in EIAV entry. To identify the endocytic pathway involved in EIAV entry, we examined the entry requirements for EIAV into two different cells: equine dermal (ED) cells and primary equine endothelial cells. We investigated the entry mechanism of several strains of EIAV and found that both macrophage-tropic and tissue culture-adapted strains utilize clathrin-coated pits for entry. In contrast, a superinfecting strain of EIAV, EIAV(vMA-1c), utilizes two mechanisms of entry. In cells such as ED cells that EIAV(vMA-1c) is able to superinfect, viral entry is pH independent and appears to be mediated by plasma membrane fusion, whereas in cells where no detectable superinfection occurs, EIAV(vMA-1c) entry that is low-pH dependent occurs through clathrin-coated pits in a manner similar to wild-type virus. Regardless of the mechanism of entry being utilized, the internalization kinetics of EIAV is rapid with 50% of cell-associated virions internalizing within 60 to 90 min. Cathepsin inhibitors did not prevent EIAV entry, suggesting that the low-pH step required by wild-type EIAV is not required to activate cellular cathepsins.",,"['Brindley, Melinda A.', 'Maury, Wendy']",,,,
,PMC,Evidence of the Recombinant Origin of a Bat Severe Acute Respiratory Syndrome (SARS)-Like Coronavirus and Its Implications on the Direct Ancestor of SARS Coronavirus,http://dx.doi.org/10.1128/JVI.01926-07,PMC2258724,,,"Bats have been identified as the natural reservoir of severe acute respiratory syndrome (SARS)-like and SARS coronaviruses (SLCoV and SCoV). However, previous studies suggested that none of the currently sampled bat SLCoVs is the descendant of the direct ancestor of SCoV, based on their relatively distant phylogenetic relationship. In this study, evidence of the recombinant origin of the genome of a bat SLCoV is demonstrated. We identified a potential recombination breakpoint immediately after the consensus intergenic sequence between open reading frame 1 and the S coding region, suggesting the replication intermediates may participate in the recombination event, as previously speculated for other CoVs. Phylogenetic analysis of its parental regions suggests the presence of an uncharacterized SLCoV lineage that is phylogenetically closer to SCoVs than any of the currently sampled bat SLCoVs. Using various Bayesian molecular-clock models, interspecies transfer of this SLCoV lineage from bats to the amplifying host (e.g., civets) was estimated to have happened a median of 4.08 years before the SARS outbreak. Based on this relatively short window period, we speculate that this uncharacterized SLCoV lineage may contain the direct ancestor of SCoV. This study sheds light on the possible host bat species of the direct ancestor of SCoV, providing valuable information on the scope and focus of surveillance for the origin of SCoV.",,"['Hon, Chung-Chau', 'Lam, Tsan-Yuk', 'Shi, Zheng-Li', 'Drummond, Alexei J.', 'Yip, Chi-Wai', 'Zeng, Fanya', 'Lam, Pui-Yi', 'Leung, Frederick Chi-Ching']",,,,
,PMC,Activation of p90 Ribosomal S6 Kinase by ORF45 of Kaposi's Sarcoma-Associated Herpesvirus and Its Role in Viral Lytic Replication,http://dx.doi.org/10.1128/JVI.02119-07,PMC2258723,,,"The extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway is essential for infection by a variety of viruses. The p90 ribosomal S6 kinases (RSKs) are direct substrates of ERK and functional mediators of ERK MAPK signaling, but their roles in viral infection have never been examined. We demonstrate that ORF45 of Kaposi's sarcoma-associated herpesvirus (KSHV) interacts with RSK1 and RSK2 and strongly stimulates their kinase activities. The activation of RSK by ORF45 is correlated with ERK activation but does not require MEK. We further demonstrate that RSK1/RSK2 is activated during KSHV primary infection and reactivation from latency; a subset of RSK1/RSK2 is present in the viral replication compartment in the nucleus. Depletion of RSK1/RSK2 by small interfering RNA or the specific inhibitor BI-D1870 suppresses KSHV lytic gene expression and progeny virion production, suggesting an essential role of RSK1/RSK2 in KSHV lytic replication.",,"['Kuang, Ersheng', 'Tang, Qiyi', 'Maul, Gerd G.', 'Zhu, Fanxiu']",,,,
,PMC,Independent and Cooperative Antiviral Actions of Beta Interferon and Gamma Interferon against Herpes Simplex Virus Replication in Primary Human Fibroblasts,http://dx.doi.org/10.1128/JVI.01649-07,PMC2258722,,,"Type I and type II interferons (IFNs) act in synergy to inhibit the replication of a variety of viruses, including herpes simplex virus (HSV). To understand the mechanism of this effect, we have analyzed the transcriptional profiles of primary human fibroblast cells that were first treated with IFN-β1, IFN-γ, or a combination of both and then subsequently infected with HSV-1. We have identified two types of synergistic activities in the gene expression patterns induced by IFN-β1 and IFN-γ that may contribute to inhibition of HSV-1 replication. The first is defined as “synergy by independent action,” in which IFN-β1 and IFN-γ induce distinct gene categories. The second, “synergy by cooperative action,” is a term that describes the positive interaction between IFN-β1 and IFN-γ as defined by a two-way analysis of variance. This form of synergy leads to a much higher level of expression for a subset of genes than is seen with either interferon alone. The cooperatively induced genes by IFN-β1 and IFN-γ include those involved in apoptosis, RNA degradation, and the inflammatory response. Furthermore, the combination of IFN-β1 and IFN-γ induces significantly more apoptosis and inhibits HSV-1 gene expression and DNA replication significantly more than treatment with either interferon alone. Taken together, these data suggest that IFN-β1 and IFN-γ work both independently and cooperatively to create an antiviral state that synergistically inhibits HSV-1 replication in primary human fibroblasts and that cooperatively induced apoptosis may play a role in the synergistic effect on viral replication.",,"['Peng, Tao', 'Zhu, Jia', 'Hwangbo, Yon', 'Corey, Lawrence', 'Bumgarner, Roger E.']",,,,
,PMC,Chemical modification: the key to clinical application of RNA interference?,http://dx.doi.org/10.1172/JCI33483,PMC2096450,,,"RNA interference provides a potent and specific method for controlling gene expression in human cells. To translate this potential into a broad new family of therapeutics, it is necessary to optimize the efficacy of the RNA-based drugs. As discussed in this Review, it might be possible to achieve this optimization using chemical modifications that improve their in vivo stability, cellular delivery, biodistribution, pharmacokinetics, potency, and specificity.",,"Corey, David R.",,,,
,PMC,Nonviral delivery of synthetic siRNAs in vivo,http://dx.doi.org/10.1172/JCI33494,PMC2096447,,,"Sequence-specific gene silencing using small interfering RNA (siRNA) is a Nobel prize–winning technology that is now being evaluated in clinical trials as a potentially novel therapeutic strategy. This article provides an overview of the major pharmaceutical challenges facing siRNA therapeutics, focusing on the delivery strategies for synthetic siRNA duplexes in vivo, as this remains one of the most important issues to be resolved. This article also highlights the importance of understanding the genocompatibility/toxicogenomics of siRNA delivery reagents in terms of their impact on gene-silencing activity and specificity. Collectively, this information is essential for the selection of optimally acting siRNA delivery system combinations for the many proposed applications of RNA interference.",,"['Akhtar, Saghir', 'Benter, Ibrahim F.']",,,,
,PMC,Efficient and rapid protein expression and purification of small high disulfide containing sweet protein brazzein in E. coli,http://dx.doi.org/10.1016/j.pep.2007.11.009,PMC2374762,,,"Brazzein protein comes from an edible fruit, which has a long history of being a staple in the local human diet in Africa. The attractive features of brazzein as a potential commercial sweetener include its small size (53 amino acid residues), its stability over wide ranges of temperature and pH, and the similarity of its sweetness to sucrose. Heterologous production of brazzein is complicated by the fact that the protein contains four disulfide bridges and requires a specific N-terminal sequence. Our previous protocol for producing the protein from Escherichia coli involved several steps with low overall yield: expression as a fusion protein, denaturation and renaturation, oxidation of the cysteines, and cleavage by cyanogen bromide at an engineered methionine adjacent to the desired N-terminus. The new protocol described here, which is much faster and leads to a higher yield of native protein, involves the production of brazzein in E. coli as a fusion with SUMO. The isolated protein product contains the brazzein domain folded with correct disulfide bonds formed and is then cleaved with a specific SUMO protease to liberate native brazzein. This protocol represents an important advancement that will enable more efficient research into the interaction between brazzein and the receptor as well as investigations to test the potential of brazzein as a commercially viable natural low calorie sweetener.",,"['Assadi-Porter, Fariba', 'Patry, Sammy', 'Markley, John L.']",,,,
,PMC,Correlation of immunogenicities and in vitro expression levels of recombinant modified vaccinia virus Ankara HIV vaccines,http://dx.doi.org/10.1016/j.vaccine.2007.11.036,PMC2262837,,,"The purpose of the present study was to correlate the in vitro level of HIV Env expression by recombinant modified vaccinia virus Ankara (rMVA) with immunogenicity in mice. A 5-fold difference in Env synthesis was achieved at the translational level by the presence or absence of an out-of-frame initiation codon upstream of the env gene. This perturbation had no effect on the size or processing of Env. In contrast to the variation in Env synthesis, the rMVAs produced similar amounts of HIV Gag, which were expressed from identical cassettes. Mice immunized with the higher Env expressing rMVAs had about 15-fold higher titers of Env antibodies and several fold higher frequencies of Env-specific CD8+ and CD4+ T cells than mice immunized with the low expresser. The greater immune response achieved by high expression was maintained over a 100-fold dose range. Importantly, enhanced Env immune responses did not come at the expense of lower Gag T cell responses. These data suggest that for high immunogenicity, rMVAs should be engineered to produce the most recombinant protein that can be achieved without compromising the growth and stability of the rMVA.",,"['Wyatt, Linda S.', 'Earl, Patricia L.', 'Vogt, Jennifer', 'Eller, Leigh Anne', 'Chandran, Dev', 'Liu, Jinyan', 'Robinson, Harriet L.', 'Moss, Bernard']",,,,
,PMC,Cell-surface processing of extracellular human immunodeficiency virus type 1 Vpr by proprotein convertases,http://dx.doi.org/10.1016/j.virol.2007.10.036,PMC3955186,,,"Increasing evidence suggests that extracellular Vpr could contribute to HIV pathogenesis through its effect on bystander cells. Soluble forms of Vpr have been detected in the sera and cerebrospinal fluids of HIV-1-infected patients, and in vitro studies have implicated extracellular Vpr as an effector of cellular responses, including G2 arrest, apoptosis and induction of cytokines and chemokines production, presumably through its ability to transduce into multiple cell types. However, the mechanism underlying Vpr release from HIV-1-producing cells remains undefined and the biological modifications that the extracellular protein may undergo are largely unknown. We provide evidence indicating that soluble forms of Vpr are present in the extracellular medium of HIV-1-producing cells. Release of Vpr in the extracellular medium did not originate from decaying or disrupted HIV-1 virions that package Vpr but rather appeared associated with HIV-1-mediated cytopathicity. Interestingly, Vpr was found to undergo proteolytic processing at a very well conserved proprotein convertase (PC) cleavage site, R(85)QRR(88)↓, located within the functionally important C-terminal arginine-rich domain of the protein. Vpr processing occurred extracellularly upon close contact to cells and most likely involved a cell surface-associated PC. Consistently, PC inhibitors suppressed Vpr processing, while expression of extracellular matrix-associated PC5 and PACE4 enhanced Vpr cleavage. PC-mediated processing of extracellular Vpr led to the production of a truncated Vpr product that was defective for the induction of cell cycle arrest and apoptosis when expressed in human cells. Collectively, these results suggest that cell surface processing of extracellular Vpr by PCs might regulate the levels of active soluble Vpr.",,"['Xiao, Yong', 'Chen, Gang', 'Richard, Jonathan', 'Rougeau, Nicole', 'Li, Hongshan', 'Seidah, Nabil G.', 'Cohen, Éric A.']",,,,
,PMC,CYTOPLASMIC VACUOLIZATION RESPONSES TO CYTOPATHIC BOVINE VIRAL DIARRHOEA VIRUS,http://dx.doi.org/10.1016/j.virusres.2007.10.017,PMC2289992,,,"Bovine Viral Diarrhea Virus (BVDV) is a positive sense, single-stranded RNA virus which exhibits two biotypes in standard cell culture systems. The cytopathic strains of this virus (cpBVDV) induce dramatic cytoplasmic vacuolization in cell cultures, while infection with the non-cytopathic (NCP-BVDV) strains produces no overt changes in the host cells. Our results show that extensive cytoplasmic vacuolization is the earliest morphological change in response to cpBVDV infection in MDBK cells. Cells with extensive vacuolization showed no co-existing chromatin condensation, caspase activation, or loss of membrane integrity. In addition, the caspase inhibitor (zVAD-fmk), although improving cell viability of infected cells from 6.7±2.2% to 18.8±2.2%, did not prevent vacuolization. On the ultrastructural level, the virus-induced cytoplasmic vacuoles are single membrane structures containing organelles and cellular debris, which appear capable of fusing with other vacuoles and engulfing surrounding cytoplasmic materials. LysoTracker Red which marks lysosomes did not stain the virus-induced cytoplasmic vacuoles. In addition, this lysosomal dye could be observed in the cytoplasm of vacuolized cells, suggesting a lysosomal abnormality. Our data demonstrate that cpBVDV induced a novel cell death pathway in MDBK cells that is primarily associated with lysosomal dysfunction and the formation of phagocytic cytoplasmic vacuoles, and this mode of cell death is different from apoptosis and necrosis.",,"['Birk, Alexander V.', 'Dubovi, Edward J.', 'Cohen-Gould, Leona', 'Donis, Ruben', 'Szeto, Hazel. H.']",,,,
,PMC,Development of elderly care services in Hong Kong: challenges and creative solutions,http://dx.doi.org/10.7861/clinmedicine.7-6-548,PMC4954358,,,"Elderly care services in Hong Kong began in the mid-1970s, with health and social services modelled on the UK experience. A major difference is the lack of a well-developed primary care system. As a result, geriatric service has evolved to encompass primary care, to include outreach geriatrics and psychogeriatric support to long-term residential care homes as well as frail elderly people living at home. There is room for innovation in the provision of community care, led by geriatricians, especially in management of chronic disease, incorporating the components of self management and use of telemedicine. Various models could be developed and evaluated to define which best meet the needs of the ageing population. The results would guide future government policy for health and social services for the elderly population in the community setting.",,"Woo, Jean",,,,
,PMC,Your liberty or your life. Talking Point on public health versus civil liberties,http://dx.doi.org/10.1038/sj.embor.7401133,PMC2267247,,,,,"Annas, George J",,,,
,PMC,The continuing tensions between individual rights and public health. Talking Point on public health versus civil liberties,http://dx.doi.org/10.1038/sj.embor.7401134,PMC2267241,,,,,"Bayer, Ronald",,,,
,PMC,Contact tracing to control infectious disease: when enough is enough,,PMC3428220,,,"Contact tracing (also known as partner notification) is a primary means of controlling infectious diseases such as tuberculosis (TB), human immunodeficiency virus (HIV), and sexually transmitted diseases (STDs). However, little work has been done to determine the optimal level of investment in contact tracing. In this paper, we present a methodology for evaluating the appropriate level of investment in contact tracing. We develop and apply a simulation model of contact tracing and the spread of an infectious disease among a network of individuals in order to evaluate the cost and effectiveness of different levels of contact tracing. We show that contact tracing is likely to have diminishing returns to scale in investment: incremental investments in contact tracing yield diminishing reductions in disease prevalence. In conjunction with a cost-effectiveness threshold, we then determine the optimal amount that should be invested in contact tracing. We first assume that the only incremental disease control is contact tracing. We then extend the analysis to consider the optimal allocation of a budget between contact tracing and screening for exogenous infection, and between contact tracing and screening for endogenous infection. We discuss how a simulation model of this type, appropriately tailored, could be used as a policy tool for determining the appropriate level of investment in contact tracing for a specific disease in a specific population. We present an example application to contact tracing for chlamydia control.",,"['Armbruster, Benjamin', 'Brandeau, Margaret L.']",,,,
,PMC,Immune responses against severe acute respiratory syndrome coronavirus induced by virus-like particles in mice,http://dx.doi.org/10.1111/j.1365-2567.2007.02676.x,PMC2266036,,,"Virus-like particles (VLPs) represent a promising vaccine against severe acute respiratory syndrome coronavirus (SARS CoV). In this study, recombinant baculovirus vAcS and vAcME were constructed to express the S protein and the M and E proteins of SARS CoV, respectively. Electron microscope analysis demonstrated the formation of VLPs in vAcME and vAcS coinfected insect cells. Mice immunized four times with VLPs developed high antibody titres against SARS CoV. In addition, VLPs elicited cell-mediated immunity as demonstrated by enhanced interferon-γ and interleukin-4 production. VLPs also conferred protective immunity against the infection of Spike protein pseudotyped murine leukaemia virus. Our findings demonstrate that SARS CoV VLPs are immunogenic and can elicit strong SARS CoV-specific humoral and cellular immune responses in mice. This is the first study describing the immunogenicity of SARS CoV VLPs, providing valuable data for developing a protective vaccine against SARS CoV infection.",,"['Lu, Xinya', 'Chen, Yao', 'Bai, Bingke', 'Hu, Hui', 'Tao, Ling', 'Yang, Jihong', 'Chen, Jianjun', 'Chen, Ze', 'Hu, Zhihong', 'Wang, Hanzhong']",,,,
,PMC,Differential expression of adhesion molecules and chemokines between nasal and small intestinal mucosae: implications for T- and sIgA(+) B-lymphocyte recruitment,http://dx.doi.org/10.1111/j.1365-2567.2007.02671.x,PMC2266035,,,"Nasal and small intestinal mucosae are the first sites of contact with infectious agents and the sites of T-cell-mediated and secreted immunoglobulin A (IgA)-mediated defences against pathogens. We investigated the factors controlling the infiltration of CD3(+) T lymphocytes and surface IgA(+) (sIgA(+)) B lymphocytes into swine epithelium and lamina propria (LP) within and between these two mucosal effector sites. Vascular addressins, vascular cell adhesion molecule 1 and mucosal addressin cell adhesion molecule-1 were reciprocally expressed in both mucosae. Strong expression of α(4)β(1) relative to α(4)β(7) was characteristic of CD3(+) T cells in nasal mucosa LP and epithelium and of sIgA(+) cells in nasal mucosa epithelium. The same profile was observed on corresponding blood cells. Conversely, higher levels of integrins β(7) and α(4)β(7) than α(4)β(1) were characteristic of CD3(+) T cells and sIgA(+) cells in the small intestine. However, about 40% of the LP-activated sIgA(+) cells displayed sIgA(high), integrin α(4) [Image: see text] and integrin α(4) [Image: see text] expression. Whereas CCL19, CXCL12, CCL21 and CCL28 messenger RNAs were similarly expressed in both mucosae, CCL25 messenger RNA was only expressed in the small intestine. Thus, the nasal and small intestine mucosae represent separate compartments for infiltration by CD3(+) T cells and sIgA(+) effector cells, with the exception of a population of small intestine activated sIgA(+) cells, which may gain access to both mucosae.",,"['Bourges, Dorothée', 'Chevaleyre, Claire', 'Wang, CaiHong', 'Berri, Mustapha', 'Zhang, XiaoMei', 'Nicaise, Laetitia', 'Meurens, François', 'Salmon, Henri']",,,,
,PMC,Pathology and virus dispersion in cynomolgus monkeys experimentally infected with severe acute respiratory syndrome coronavirus via different inoculation routes,http://dx.doi.org/10.1111/j.1365-2613.2007.00567.x,PMC2517337,,,"Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes SARS. The pathogenic mechanisms of SARS-CoV remain poorly understood. Six cynomolgus monkeys were inoculated with the HKU39849 isolate of SARS-CoV via four routes. After intranasal inoculation, the virus was isolated from respiratory swabs on days 2–7 postinoculation (p.i.) and virus genome was detected in intestinal tissues on day 7 p.i. Virus was not detected after intragastric inoculation. After intravenous inoculation, infectious virus was isolated from rectal swabs, and virus antigen was detected in intestinal cells on day 14 p.i. After intratracheal (i.t.) inoculation, virus antigen-positive alveolar cells and macrophages were found in lung and infectious virus was detected in lymphoid and intestinal tissues. The peribronchial lymph nodes showed evidence of an immune response. Lung tissue and/or fluid and/or the peribronchial lymph node of the intratracheally inoculated animals had high TNF-α, IL-8 and IL-12 levels. SARS lung lesions are only generated in monkeys by i.t. inoculation. The virus appears to spread into and perhaps via the intestinal and lymphatic systems. It has been suggested previously that viraemia may cause intestinal infections in SARS patients.",,"['Nagata, Noriyo', 'Iwata, Naoko', 'Hasegawa, Hideki', 'Sato, Yuko', 'Morikawa, Shigeru', 'Saijo, Masayuki', 'Itamura, Shigeyuki', 'Saito, Takehiko', 'Ami, Yasushi', 'Odagiri, Takato', 'Tashiro, Masato', 'Sata, Tetsutaro']",,,,
,PMC,"The Autodisplay Story, from Discovery to Biotechnical and Biomedical Applications",http://dx.doi.org/10.1128/MMBR.00011-07,PMC2168652,,,"Summary: Among the pathways used by gram-negative bacteria for protein secretion, the autotransporter pathway represents a solution of impressive simplicity. Proteins are transported, independent of their nature as recombinant or native passengers, as long as the coding nucleotide sequence is inserted in frame between those of an N-terminal signal peptide and a C-terminal domain, referred to as the β-barrel of the outer membrane translocation unit. The immunoglobulin A1 (IgA1) protease from Neisseria gonorrhoeae was the first identified member of the autotransporter family of secreted proteins. The IgA1 protease was employed in initial experiments investigating autotransporter-mediated surface display of recombinant proteins and to investigate structural and functional requirements. Various other autotransporter proteins have since been described, and the autodisplay system was developed on the basis of the natural Escherichia coli autotransporter protein AIDA-I (adhesin involved in diffuse adherence). Autodisplay has been used for the surface display of random peptide libraries to successfully screen for novel enzyme inhibitors. The autodisplay system was also used for the surface display of functional enzymes, including esterases, oxidoreductases, and electron transfer proteins. Whole E. coli cells displaying enzymes have been utilized to efficiently synthesize industrially important rare organic compounds with specific chirality. Autodisplay of epitopes on the surface of attenuated Salmonella carriers has also provided a novel way to induce immune protection after oral vaccination. This review summarizes the structural and functional features of the autodisplay system, illustrating its discovery and most recent applications. Autodisplay facilitates the export of more than 100,000 recombinant molecules per single cell and permits the oligomerization of subunits on the cell surface as well as the incorporation of inorganic prosthetic groups after transport of apoproteins onto the bacterial surface without disturbing bacterial integrity or viability. We discuss future biotechnical and biomedical applications in the light of these achievements.",,"['Jose, Joachim', 'Meyer, Thomas F.']",,,,
,PMC,Human ribosomal protein L13a is dispensable for canonical ribosome function but indispensable for efficient rRNA methylation,http://dx.doi.org/10.1261/rna.694007,PMC2080596,,,"Previously, we demonstrated that treatment of monocytic cells with IFN-γ causes release of ribosomal protein L13a from the 60S ribosome and subsequent translational silencing of Ceruloplasmin (Cp) mRNA. Here, evidence using cultured cells demonstrates that Cp mRNA silencing is dependent on L13a and that L13a-deficient ribosomes are competent for global translational activity. Human monocytic U937 cells were stably transfected with two different shRNA sequences for L13a and clonally selected for more than 98% abrogation of total L13a expression. Metabolic labeling of these cells showed rescue of Cp translation from the IFN-γ mediated translational silencing activity. Depletion of L13a caused significant reduction of methylation of ribosomal RNA and of cap-independent translation mediated by Internal Ribosome Entry Site (IRES) elements derived from p27, p53, and SNAT2 mRNAs. However, no significant differences in the ribosomal RNA processing, polysome formation, global translational activity, translational fidelity, and cell proliferation were observed between L13a-deficient and wild-type control cells. These results support the notion that ribosome can serve as a depot for releasable translation-regulatory factors unrelated to its basal polypeptide synthetic function. Unlike mammalian cells, the L13a homolog in yeast is indispensable for growth. Thus, L13a may have evolved from an essential ribosomal protein in lower eukaryotes to having a role as a dispensable extra-ribosomal function in higher eukaryotes.",,"['Chaudhuri, Sujan', 'Vyas, Keyur', 'Kapasi, Purvi', 'Komar, Anton A.', 'Dinman, Jonathan D.', 'Barik, Sailen', 'Mazumder, Barsanjit']",,,,
,PMC,Traditional smallpox vaccination with reduced risk of inadvertent contact spread by administration of povidone iodine ointment,http://dx.doi.org/10.1016/j.vaccine.2007.10.070,PMC2323604,,,"One concern with traditional smallpox vaccination is inadvertent spread of virus to atopic or immunocompromised contacts. To reduce this risk, we tested the ability of povidone iodine to inactivate infectious virus at the vaccination site beginning at 7 days after transcutaneous smallpox vaccination. This ointment rapidly inactivated virus on the skin without reducing neutralizing antibody titers or antiviral T cell responses. Moreover, there was no delay in healing/eschar separation following povidone iodine application. Together, this indicates that administration of an antiviral/antimicrobial cream can effectively block virus shedding after traditional smallpox vaccination and reduce the risks of autoinoculation or contact spread.",,"['Hammarlund, Erika', 'Lewis, Matthew W.', 'Hanifin, Jon', 'Simpson, Eric L.', 'Carlson, Nichole E.', 'Slifka, Mark K.']",,,,
,PMC,Generation and characterization of a preventive and therapeutic HPV DNA vaccine,http://dx.doi.org/10.1016/j.vaccine.2007.11.019,PMC2258233,,,"Cervical cancer is one of the most common cancers in women worldwide. Persistent infection with human papillomavirus (HPV) is considered to be the etiological factor for cervical cancer. Therefore, an effective vaccine against HPV infections may lead to the control of cervical cancer. An ideal HPV vaccine should aim to generate both humoral immune response to prevent new infections as well as cell-mediated immunity to eliminate established infection or HPV-related disease. In the current study, we have generated a potential preventive and therapeutic HPV DNA vaccine using human calreticulin (CRT) linked to HPV16 early proteins, E6 and E7 and the late protein L2 (hCRTE6E7L2). We found that vaccination with hCRTE6E7L2 DNA vaccine induced a potent E6/E7-specific CD8+ T cell immune response, resulting in a significant therapeutic effect against E6/E7 expressing tumor cells. In addition, vaccination with hCRTE6E7L2 DNA generated significant L2-specific neutralizing antibody responses, protecting against pseudovirion infection. Thus, the hCRTE6E7L2 DNA vaccines are capable of generating potent preventive and therapeutic effects in vaccinated mice. Our data has significant clinical implications.",,"['Kim, Daejin', 'Gambhira, Ratish', 'Karanam, Balasubramanyam', 'Monie, Archana', 'Hung, Chien-Fu', 'Roden, Richard', 'Wu, T.-C.']",,,,
,PMC,Infectious Bronchitis Viruses with a Novel Genomic Organization,http://dx.doi.org/10.1128/JVI.01694-07,PMC2258726,,,"A number of novel infectious bronchitis viruses (IBVs) were previously identified in commercial poultry in Australia, where they caused significant economic losses. Since there has been only limited characterization of these viruses, we investigated the genomic and phenotypic differences between these novel IBVs and other, classical IBVs. The 3′ 7.5 kb of the genomes of 17 Australian IBV strains were sequenced, and growth properties of 6 of the strains were compared. Comparison of sequences of the genes coding for structural and nonstructural proteins revealed the existence of two IBV genotypes: classical and novel. The genomic organization of the classical IBVs was typical of those of other group III coronaviruses: 5′-Pol-S-3a-3b-E-M-5a-5b-N-untranslated region (UTR)-3′. However, the novel IBV genotype lacked either all or most of the genes coding for nonstructural proteins at the 3′ end of the genome and had a unique open reading frame, X1. The gene order was either 5′-Pol-S-X1-E-M-N-UTR-3′ or 5′-Pol-S-X1-E-M-5b-N-UTR-3′. Phenotypically, novel and classical IBVs also differed; novel IBVs grew at a slower rate and reached lower titers in vitro and in vivo and were markedly less immunogenic in chicks. Although the novel IBVs induced histopathological lesions in the tracheas of infected chicks that were comparable to those induced by classical strains, they did not induce lesions in the kidneys. This study has demonstrated for the first time the existence of a naturally occurring IBV genotype devoid of some of the genes coding for nonstructural proteins and has also indicated that all of the accessory genes are dispensable for the growth of IBV and that such viruses are able to cause clinical disease and economic loss. The phylogenic differences between these novel IBVs and other avian coronaviruses suggest a reservoir host distinct from domestic poultry.",,"['Mardani, Karim', 'Noormohammadi, Amir H.', 'Hooper, Peter', 'Ignjatovic, Jagoda', 'Browning, Glenn F.']",,,,
,PMC,SARS coronavirus Accessory Proteins,http://dx.doi.org/10.1016/j.virusres.2007.10.009,PMC2720074,,,"The emergence of the severe acute respiratory syndrome coronavirus (SARS-CoV) has led to a renewed interest in studying the role of accessory proteins in regulating coronavirus infections in the natural host. A significant body of evidence has accumulated in the area of SARS-CoV and host interactions that indicate that the accessory proteins might play an important role in modulating the host response to virus infection and thereby, contribute to pathogenesis. In this review, we have compiled the current knowledge about SARS-CoV accessory proteins, obtained from studies in cell culture systems, reverse genetics and animal models, to shed some light into the possible role of these proteins in the propagation and virulence of SARS-CoV in its natural host. We conclude by providing some questions for future studies that will greatly advance our knowledge about the biological significance and contributions of the accessory proteins in the development of SARS in humans.",,"['Narayanan, Krishna', 'Huang, Cheng', 'Makino, Shinji']",,,,
,PMC,Using physical barriers to reduce the spread of respiratory viruses,http://dx.doi.org/10.1136/bmj.39406.511817.BE,PMC2190279,,,"Handwashing and wearing masks, gloves, and gowns are highly effective",,"Dawes, Martin",,,,
,PMC,Physical interventions to interrupt or reduce the spread of respiratory viruses: systematic review,http://dx.doi.org/10.1136/bmj.39393.510347.BE,PMC2190272,,,"Objective To systematically review evidence for the effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. Data extraction Search strategy of the Cochrane Library, Medline, OldMedline, Embase, and CINAHL, without language restriction, for any intervention to prevent transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection, and hygiene). Study designs were randomised trials, cohort studies, case-control studies, and controlled before and after studies. Data synthesis Of 2300 titles scanned 138 full papers were retrieved, including 49 papers of 51 studies. Study quality was poor for the three randomised controlled trials and most of the cluster randomised controlled trials; the observational studies were of mixed quality. Heterogeneity precluded meta-analysis of most data except that from six case-control studies. The highest quality cluster randomised trials suggest that the spread of respiratory viruses into the community can be prevented by intervening with hygienic measures aimed at younger children. Meta-analysis of six case-control studies suggests that physical measures are highly effective in preventing the spread of SARS: handwashing more than 10 times daily (odds ratio 0.45, 95% confidence interval 0.36 to 0.57; number needed to treat=4, 95% confidence interval 3.65 to 5.52); wearing masks (0.32, 0.25 to 0.40; NNT=6, 4.54 to 8.03); wearing N95 masks (0.09, 0.03 to 0.30; NNT=3, 2.37 to 4.06); wearing gloves (0.43, 0.29 to 0.65; NNT=5, 4.15 to 15.41); wearing gowns (0.23, 0.14 to 0.37; NNT=5, 3.37 to 7.12); and handwashing, masks, gloves, and gowns combined (0.09, 0.02 to 0.35; NNT=3, 2.66 to 4.97). The incremental effect of adding virucidals or antiseptics to normal handwashing to decrease the spread of respiratory disease remains uncertain. The lack of proper evaluation of global measures such as screening at entry ports and social distancing prevent firm conclusions being drawn. Conclusion Routine long term implementation of some physical measures to interrupt or reduce the spread of respiratory viruses might be difficult but many simple and low cost interventions could be useful in reducing the spread.",,"['Jefferson, Tom', 'Foxlee, Ruth', 'Mar, Chris Del', 'Dooley, Liz', 'Ferroni, Eliana', 'Hewak, Bill', 'Prabhala, Adi', 'Nair, Sree', 'Rivetti, Alex']",,,,
,PMC,"Experimental coronavirus retinopathy (ECOR): Retinal degeneration susceptible mice have an augmented interferon and chemokine (CXCL9, CXCL10) response early after virus infection",http://dx.doi.org/10.1016/j.jneuroim.2007.09.032,PMC2562577,,,"Mouse hepatitis virus induces a biphasic disease in BALB/c mice that consists of an acute retinitis followed by progression to a chronic retinal degeneration with autoimmune reactivity. Retinal degeneration resistant CD-1 mice do not develop the late phase. What host factors contribute to the distinct responses to the virus are unknown. Herein, we show that IFN-α, IFN-β and IFN-γ act in concert as part of the innate immune response to the retinal infection. At day 2, high serum levels of IFN-γ, CXCL9 and CXCL10, were detected in BALB/c mice. Moreover, elevated levels of CXCL9 and CXCL10 gene expression were detected in retinal tissue. Although IFN-γ and the chemokines were detected in CD-1 mice, they were at significantly lower levels compared to BALB/c mice. These augmented innate responses observed correlated with the development of autoimmune reactivity and retinal degeneration and thus may contribute to the pathogenic processes.",,"['Detrick, Barbara', 'Lee, Maria Teresa', 'Chin, Marian S.', 'Hooper, Laura C.', 'Chan, Chi-Chao', 'Hooks, John J.']",,,,
,PMC,SARS-CoV replicates in primary human alveolar type II cell cultures but not in type I-like cells,http://dx.doi.org/10.1016/j.virol.2007.09.045,PMC2312501,,,"Severe acute respiratory syndrome (SARS) is a disease characterized by diffuse alveolar damage. We isolated alveolar type II cells and maintained them in a highly differentiated state. Type II cell cultures supported SARS-CoV replication as evidenced by RT-PCR detection of viral subgenomic RNA and an increase in virus titer. Virus titers were maximal by 24 hours and peaked at approximately 10(5) pfu/mL. Two cell types within the cultures were infected. One cell type was type II cells, which were positive for SP-A, SP-C, cytokeratin, a type II cell-specific monoclonal antibody, and Ep-CAM. The other cell type was composed of spindle-shaped cells that were positive for vimentin and collagen III and likely fibroblasts. Viral replication was not detected in type I-like cells or macrophages. Hence, differentiated adult human alveolar type II cells were infectible but alveolar type I-like cells and alveolar macrophages did not support productive infection.",,"['Mossel, Eric C.', 'Wang, Jieru', 'Jeffers, Scott', 'Edeen, Karen E.', 'Wang, Shuanglin', 'Cosgrove, Gregory P.', 'Funk, C. Joel', 'Manzer, Rizwan', 'Miura, Tanya A.', 'Pearson, Leonard D.', 'Holmes, Kathryn V.', 'Mason, Robert J.']",,,,
,PMC,Uncoupling RNA virus replication from transcription via the polymerase: functional and evolutionary insights,http://dx.doi.org/10.1038/sj.emboj.7601931,PMC2140117,,,"Many eukaryotic positive-strand RNA viruses transcribe subgenomic (sg) mRNAs that are virus-derived messages that template the translation of a subset of viral proteins. Currently, the premature termination (PT) mechanism of sg mRNA transcription, a process thought to operate in a variety of viruses, is best understood in tombusviruses. The viral RNA elements involved in regulating this mechanism have been well characterized in several systems; however, no corresponding protein factors have been identified yet. Here we show that tombusvirus genome replication can be effectively uncoupled from sg mRNA transcription in vivo by C-terminal modifications in its RNA-dependent RNA polymerase (RdRp). Systematic analysis of the PT transcriptional pathway using viral genomes harboring mutant RdRps revealed that the C-terminus functions primarily at an early step in this mechanism by mediating both efficient and accurate production of minus-strand templates for sg mRNA transcription. Our results also suggest a simple evolutionary scheme by which the virus could gain or enhance its transcriptional activity, and define global folding of the viral RNA genome as a previously unappreciated determinant of RdRp evolution.",,"['Wu, Baodong', 'White, K Andrew']",,,,
,PMC,Sensitive and Specific Enzyme-Linked Immunosorbent Assay Using Chemiluminescence for Detection of Severe Acute Respiratory Syndrome Viral Infection,http://dx.doi.org/10.1128/JCM.01006-07,PMC2224272,,,"Here we report the development of a more-sensitive immunoassay for severe acute respiratory syndrome (SARS) based on an enzyme-linked immunosorbent assay using chemiluminescence (CLEIA) to detect the viral nucleocapsid (N) antigen in nasopharyngeal aspirate (NPA) from patients infected with SARS coronavirus (CoV). The CLEIA was established with an optical combination of monoclonal antibodies (MAbs) against SARS CoV N protein prepared from mice immunized with recombinant N protein without cultivating the virus. The capture and detecting MAbs of the CLEIA reacted to the carboxyl-terminal and amino-terminal peptides of the N protein, respectively. The CLEIA was capable of detecting recombinant N protein at 1.56 pg/ml and viral N protein in SARS CoV cell culture lysates at 0.087 of 50% tissue culture infective doses/ml. The CLEIA showed no cross-reactivities to recombinant N proteins of common human CoV (229E, OC43, and NL63) or lysates of cells infected with 229E and OC43. In addition, an evaluation with 18 SARS-positive NPA samples, all confirmed SARS positive by quantitative PCR and antibodies to SARS CoV, revealed that all (18/18) were found positive by the CLEIA; thus, the sensitivity of detection was 100%. When we tested 20 SARS-negative NPA samples, the CLEIA was shown to have high specificity (100%). The sensitivity of our novel SARS CLEIA was significantly higher than the previous EIA and comparable to the other methods using reverse transcription-PCR.",,"['Fujimoto, Kotaro', 'Chan, Kwok-Hung', 'Takeda, Kazuhiko', 'Lo, Kam-Fai', 'Leung, Raymond H. K.', 'Okamoto, Takashi']",,,,
,PMC,Amiloride Derivatives Inhibit Coxsackievirus B3 RNA Replication,http://dx.doi.org/10.1128/JVI.01374-07,PMC2224459,,,"Amiloride derivatives are known blockers of the cellular Na(+)/H(+) exchanger and the epithelial Na(+) channel. More recent studies demonstrate that they also inhibit ion channels formed by a number of viral proteins. We previously reported that 5-(N-ethyl-N-isopropyl)amiloride (EIPA) modestly inhibits intracellular replication and, to a larger extent, release of human rhinovirus 2 (HRV2) (E. V. Gazina, D. N. Harrison, M. Jefferies, H. Tan, D. Williams, D. A. Anderson and S. Petrou, Antiviral Res. 67:98-106, 2005). Here, we demonstrate that amiloride and EIPA strongly inhibit coxsackievirus B3 (CVB3) RNA replication and do not inhibit CVB3 release, in contrast to our previous findings on HRV2. Passaging of plasmid-derived CVB3 in the presence of amiloride generated mutant viruses with amino acid substitutions in position 299 or 372 of the CVB3 polymerase. Introduction of either of these mutations into the CVB3 plasmid produced resistance to amiloride and EIPA, suggesting that they act as inhibitors of CVB3 polymerase, a novel mechanism of antiviral activity for these compounds.",,"['Harrison, David N.', 'Gazina, Elena V.', 'Purcell, Damian F.', 'Anderson, David A.', 'Petrou, Steven']",,,,
,PMC,"Genetic Interactions between an Essential 3′ cis-Acting RNA Pseudoknot, Replicase Gene Products, and the Extreme 3′ End of the Mouse Coronavirus Genome",http://dx.doi.org/10.1128/JVI.01690-07,PMC2224451,,,"The upstream end of the 3′ untranslated region (UTR) of the mouse hepatitis virus genome contains two essential and overlapping RNA secondary structures, a bulged stem-loop and a pseudoknot, which have been proposed to be elements of a molecular switch that is critical for viral RNA synthesis. It has previously been shown that a particular six-base insertion in loop 1 of the pseudoknot is extremely deleterious to the virus. We have now isolated multiple independent second-site revertants of the loop 1 insertion mutant, and we used reverse-genetics methods to confirm the identities of suppressor mutations that could compensate for the original insertion. The suppressors were localized to two separate regions of the genome. Members of one class of suppressor were mapped to the portions of gene 1 that encode nsp8 and nsp9, thereby providing the first evidence for specific interactions between coronavirus replicase gene products and a cis-acting genomic RNA element. The second class of suppressor was mapped to the extreme 3′ end of the genome, a result which pointed to the existence of a direct base-pairing interaction between loop 1 of the pseudoknot and the genomic terminus. The latter finding was strongly supported by phylogenetic evidence and by the construction of a deletion mutant that reduced the 3′ UTR to its minimal essential elements. Taken together, the interactions revealed by the two classes of suppressors suggest a model for the initiation of coronavirus negative-strand RNA synthesis.",,"['Züst, Roland', 'Miller, Timothy B.', 'Goebel, Scott J.', 'Thiel, Volker', 'Masters, Paul S.']",,,,
,PMC,Mapping of Equine Lentivirus Receptor 1 Residues Critical for Equine Infectious Anemia Virus Envelope Binding,http://dx.doi.org/10.1128/JVI.01393-07,PMC2224449,,,"The equine lentivirus receptor 1 (ELR1), a member of the tumor necrosis factor receptor (TNFR) protein family, has been identified as a functional receptor for equine infectious anemia virus (EIAV). Toward defining the functional interactions between the EIAV SU protein (gp90) and its ELR1 receptor, we mapped the gp90 binding domain of ELR1 by a combination of binding and functional assays using the EIAV SU gp90 protein and various chimeric receptor proteins derived from exchanges between the functional ELR1 and the nonbinding homolog, mouse herpesvirus entry mediator (murine HveA). Complementary exchanges of the respective cysteine-rich domains (CRD) between the ELR1 and murine HveA proteins revealed CRD1 as the predominant determinant of functional gp90 binding to ELR1 and also to a chimeric murine HveA protein expressed on the surface of transfected Cf2Th cells. Mutations of individual amino acids in the CRD1 segment of ELR1 and murine HveA indicated the Leu70 in CRD1 as essential for functional binding of EIAV gp90 and for virus infection of transduced Cf2Th cells. The specificity of the EIAV SU binding domain identified for the ELR1 receptor is fundamentally identical to that reported previously for functional binding of feline immunodeficiency virus SU to its coreceptor CD134, another TNFR protein. These results indicate unexpected common features of the specific mechanisms by which diverse lentiviruses can employ TNFR proteins as functional receptors.",,"['Zhang, Baoshan', 'Sun, Chengqun', 'Jin, Sha', 'Cascio, Michael', 'Montelaro, Ronald C.']",,,,
,PMC,Rotavirus Infection Induces the Phosphorylation of eIF2α but Prevents the Formation of Stress Granules,http://dx.doi.org/10.1128/JVI.01779-07,PMC2224440,,,"Early during the infection process, rotavirus causes the shutoff of cell protein synthesis, with the nonstructural viral protein NSP3 playing a vital role in the phenomenon. In this work, we have found that the translation initiation factor 2α (eIF2α) in infected cells becomes phosphorylated early after virus infection and remains in this state throughout the virus replication cycle, leading to a further inhibition of cell protein synthesis. Under these restrictive conditions, however, the viral proteins and some cellular proteins are efficiently translated. The phosphorylation of eIF2α was shown to depend on the synthesis of three viral proteins, VP2, NSP2, and NSP5, since in cells in which the expression of any of these three proteins was knocked down by RNA interference, the translation factor was not phosphorylated. The modification of this factor is, however, not needed for the replication of the virus, since mutant cells that produce a nonphosphorylatable eIF2α sustained virus replication as efficiently as wild-type cells. In uninfected cells, the phosphorylation of eIF2α induces the formation of stress granules, aggregates of stalled translation complexes that prevent the translation of mRNAs. In rotavirus-infected cells, even though eIF2α is phosphorylated these granules are not formed, suggesting that the virus prevents the assembly of these structures to allow the translation of its mRNAs. Under these conditions, some of the cellular proteins that form part of these structures were found to change their intracellular localization, with some of them having dramatic changes, like the poly(A) binding protein, which relocates from the cytoplasm to the nucleus in infected cells, a relocation that depends on the viral protein NSP3.",,"['Montero, Hilda', 'Rojas, Margarito', 'Arias, Carlos F.', 'López, Susana']",,,,
,PMC,Amino Acid Substitutions in the S2 Subunit of Mouse Hepatitis Virus Variant V51 Encode Determinants of Host Range Expansion,http://dx.doi.org/10.1128/JVI.01674-07,PMC2224421,,,"We previously described mouse hepatitis virus (MHV) variant V51 derived from a persistent infection of murine DBT cells with an expanded host range (R. S. Baric, E. Sullivan, L. Hensley, B. Yount, and W. Chen, J. Virol. 73:638-649, 1999). Sequencing of the V51 spike gene, the mediator of virus entry, revealed 13 amino acid substitutions relative to the originating MHV A59 strain. Seven substitutions were located in the amino-terminal S1 cleavage subunit, and six were located in the carboxy-terminal S2 cleavage subunit. Using targeted RNA recombination, we constructed a panel of recombinant viruses to map the mediators of host range to the six substitutions in S2, with a subgroup of four changes of particular interest. This subgroup maps to two previously identified domains within S2, a putative fusion peptide and a heptad repeat, both conserved features of class I fusion proteins. In addition to an altered host range, V51 displayed altered utilization of CEACAM1a, the high-affinity receptor for A59. Interestingly, a recombinant with S1 from A59 and S2 from V51 was severely debilitated in its ability to productively infect cells via CEACAM1a, while the inverse recombinant was not. This result suggests that the S2 substitutions exert powerful effects on the fusion trigger that normally passes from S1 to S2. These novel findings play against the existing data that suggest that MHV host range determinants are located in the S1 subunit, which harbors the receptor binding domain, or involve coordinating changes in both S1 and S2. Mounting evidence also suggests that the class I fusion mechanism may possess some innate plasticity that regulates viral host range.",,"['McRoy, Willie C.', 'Baric, Ralph S.']",,,,
,PMC,Sore throat,,PMC2943825,,,"INTRODUCTION: About 10-30% of people present to primary healthcare services with sore throat each year. The causative organisms of sore throat may be bacteria (most commonly Streptococcus) or viruses (typically rhinovirus), although it is difficult to distinguish bacterial from viral infections clinically. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to reduce symptoms of acute infective sore throat? What are the effects of interventions to prevent complications of acute infective sore throat? We searched: Medline, Embase, The Cochrane Library and other important databases up to May 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found eight systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, corticosteroids, non-steroidal anti-inflammatory drugs, paracetamol, and probiotics.",,"Kenealy, Tim",,,,
,PMC,The Krever Commission — 10 years later,http://dx.doi.org/10.1503/cmaj.071333,PMC2072981,,,,,"MD MSc, Kumanan Wilson",,,,
,PMC,Altered Levels of STAT1 and STAT3 Influence the Neuronal Response to Interferon Gamma,http://dx.doi.org/10.1016/j.jneuroim.2007.10.007,PMC2180831,,,"As immune responses in the CNS are highly regulated, cell-specific differences in IFNγ signaling may be integral in dictating the outcome of host cell responses. In comparing the response of IFNγ-treated primary neurons to control MEF, we observed that neurons demonstrated lower basal expression of both STAT1 and STAT3, the primary signal transducers responsible for IFNγ signaling. Following IFNγ treatment of these cell populations, we noted muted and delayed STAT1 phosphorylation, no detectable STAT3 phosphorylation, and a 3-10-fold lower level of representative IFNγ-responsive gene transcripts. Moreover, in response to a brief pulse of IFNγ, a steady increase in STAT1 phosphorylation and IFNγ gene expression over 48 h was observed in neurons, as compared to rapid attenuation in MEF. These distinct response kinetics in IFNγ-stimulated neurons may reflect modifications in the IFNγ negative feedback loop, which may provide a mechanism for the cell-specific heterogeneity of responses to IFNγ.",,"['Rose, R. Wesley', 'Vorobyeva, Anna G.', 'Skipworth, Jason D.', 'Nicolas, Emmanuelle', 'Rall, Glenn F.']",,,,
,PMC,Be Prepared to Use the Hot Mic to Counter Pandemics,,PMC2234314,,,,,"Hyer, Randall N.",,,,
,PMC,"Cloning, expression and characterization of ferret CXCL10",http://dx.doi.org/10.1016/j.molimm.2007.09.018,PMC5653245,,,"Chemokines and their receptors function in the recruitment and activation of cells of the immune system to sites of inflammation. As such, chemokines play an important role in mediating pathophysiological events during microbial infection. In particular, CXCL9, 10 and 11 and their cognate receptor CXCR3 have been associated with the clinical course of several infectious diseases, including severe acute respiratory syndrome (SARS) and influenza. While CXCL9, 10 and 11 share the same receptor and have overlapping functions, each can also have unique activity in host defense. The lack of a preferred characterized animal model for SARS has brought our attention to ferrets, which have been used for years in influenza studies. The lack of immunological reagents for ferrets prompted us to clone CXCL9, 10, 11 and CXCR3 and, in the case of CXCL10, to express the gene as a recombinant protein. In this study we demonstrate that endogenous ferret CXCL10 exhibits similar mRNA expression patterns in the lungs of deceased SARS patients and ferrets experimentally infected with SARS coronavirus. This study therefore represents an important step towards development of the ferret as a model for the role of CXCL9, 10 and 11:CXCR3 axis in severe viral infections.",,"['Danesh, Ali', 'Seneviratne, Charit', 'Cameron, Cheryl M.', 'Banner, David', 'Devries, Mark E.', 'Kelvin, Alyson A.', 'Xu, Luoling', 'Ran, Longsi', 'Bosinger, Steven E.', 'Rowe, Thomas', 'Czub, Marcus', 'Jonsson, Colleen B.', 'Cameron, Mark J.', 'Kelvin, David J.']",,,,
,PMC,"Epidemiological, Molecular, and Clinical Features of Enterovirus Respiratory Infections in French Children between 1999 and 2005",http://dx.doi.org/10.1128/JCM.01414-07,PMC2224256,,,"Enteroviruses (EVs) can induce nonspecific respiratory tract infections in children, but their epidemiological, virological, and clinical features remain to be assessed. In the present study, we analyzed 252 EV-related infection cases (median age of subjects, 5.1 years) diagnosed among 11,509 consecutive children visiting emergency departments within a 7-year period in the north of France. EV strains were isolated from nasopharyngeal samples by viral cell culture, identified by seroneutralization assay, and genetically compared by partial amplification and sequencing of the VP1 gene. The respiratory syndromes (79 [31%] of 252 EV infections) appeared as the second most common EV-induced pediatric pathology after meningitis (111 [44%] of 252 cases) (44 versus 31%, P < 10(−3)), contributing to lower respiratory tract infection (LRTI) in 43 (54%) of 79 EV respiratory infection cases. Bronchiolitis was the most common EV-induced LRTI (34 [43%] of 79 cases, P < 10(−3)) occurring more often in infants aged 1 to 12 months (P = 0.0002), with spring-fall seasonality. Viruses ECHO 11, 6, and 13 were the more frequently identified respiratory strains (24, 13, and 11%, respectively). The VP1 gene phylogenetic analysis showed the concomitant or successive circulation of genetically distinct EV respiratory strains (species A or B) during the same month or annual epidemic period. Our findings indicated that respiratory tract infections accounted for the 30% of EV-induced pediatric pathologies, contributing to LRTIs in 54% of these cases. Moreover, the concomitant or successive circulation of genetically distinct EV strains indicated the possibility of pediatric repeated respiratory infections within the same epidemic season.",,"['Jacques, Jérôme', 'Moret, Hélène', 'Minette, Delphine', 'Lévêque, Nicolas', 'Jovenin, Nicolas', 'Deslée, Gaetan', 'Lebargy, François', 'Motte, Jacques', 'Andréoletti, Laurent']",,,,
,PMC,The Spike Glycoprotein of Murine Coronavirus MHV-JHM Mediates Receptor-Independent Infection and Spread in the Central Nervous Systems of Ceacam1a(−/−) Mice,http://dx.doi.org/10.1128/JVI.01851-07,PMC2224565,,,"The MHV-JHM strain of the murine coronavirus mouse hepatitis virus is much more neurovirulent than the MHV-A59 strain, although both strains use murine CEACAM1a (mCEACAM1a) as the receptor to infect murine cells. We previously showed that Ceacam1a(−/−) mice are completely resistant to MHV-A59 infection (E. Hemmila et al., J. Virol. 78:10156-10165, 2004). In vitro, MHV-JHM, but not MHV-A59, can spread from infected murine cells to cells that lack mCEACAM1a, a phenomenon called receptor-independent spread. To determine whether MHV-JHM could infect and spread in the brain independent of mCEACAM1a, we inoculated Ceacam1a(−/−) mice. Although Ceacam1a(−/−) mice were completely resistant to i.c. inoculation with 10(6) PFU of recombinant wild-type MHV-A59 (RA59) virus, these mice were killed by recombinant MHV-JHM (RJHM) and a chimeric virus containing the spike of MHV-JHM in the MHV-A59 genome (SJHM/RA59). Immunohistochemistry showed that RJHM and SJHM/RA59 infected all neural cell types and induced severe microgliosis in both Ceacam1a(−/−) and wild-type mice. For RJHM, the 50% lethal dose (LD(50)) is <10(1.3) in wild-type mice and 10(3.1) in Ceacam1a(−/−) mice. For SJHM/RA59, the LD(50) is <10(1.3) in wild-type mice and 10(3.6) in Ceacam1a(−/−) mice. This study shows that infection and spread of MHV-JHM in the brain are dependent upon the viral spike glycoprotein. RJHM can initiate infection in the brains of Ceacam1a(−/−) mice, but expression of mCEACAM1a increases susceptibility to infection. The spread of infection in the brain is mCEACAM1a independent. Thus, the ability of the MHV-JHM spike to mediate mCEACAM1a-independent spread in the brain is likely an important factor in the severe neurovirulence of MHV-JHM in wild-type mice.",,"['Miura, Tanya A.', 'Travanty, Emily A.', 'Oko, Lauren', 'Bielefeldt-Ohmann, Helle', 'Weiss, Susan R.', 'Beauchemin, Nicole', 'Holmes, Kathryn V.']",,,,
,PMC,Individual space–time activity-based modelling of infectious disease transmission within a city,http://dx.doi.org/10.1098/rsif.2007.1218,PMC2607451,,,"This paper provides an example of the application of an individual space–time activity-based model (ISTAM) to the simulation of the transmission of infectious disease in Eemnes, a city in The Netherlands. Four questions were addressed: (i) how to build the whole population at the city level, (ii) how to build the structure of the activity bundles for the city, (iii) how to assign daily activity patterns to each individual, and (iv) how to simulate within-AB transmission. The model was calibrated and examples of simulation results such as dynamics of the population during a whole day, infection distribution and network analysis are presented.",,"['Yang, Yong', 'Atkinson, Peter', 'Ettema, Dick']",,,,
,PMC,A novel mechanism for LSECtin binding to Ebola virus surface glycoprotein through truncated glycans,http://dx.doi.org/10.1074/jbc.M706292200,PMC2275798,,,"LSECtin is a member of the C-type lectin family of glycan-binding receptors that is expressed on sinusoidal endothelial cells of the liver and lymph nodes. In order to compare the sugar- and pathogen-binding properties of LSECtin with those of related but more extensively characterized receptors, such as DC-SIGN, a soluble fragment of LSECtin consisting of the C-terminal carbohydrate-recognition domain has been expressed in bacteria. A biotin-tagged version of the protein was also generated and complexed with streptavidin to create tetramers. These forms of the carbohydrate-recognition domain were used to probe a glycan array and to characterize binding to oligosaccharide and glycoprotein ligands. LSECtin binds with high selectivity to glycoproteins terminating in GlcNAcβ1-2Man. The inhibition constant for this disaccharide is 3.5 μM, making it one of the best low molecular weight ligands known for any C-type lectin. As a result of the selective binding of this disaccharide unit, the receptor recognizes glycoproteins with truncated complex and hybrid N-linked glycans on glycoproteins. Glycan analysis of the surface glycoprotein of Ebola virus reveals the presence of such truncated glycans, explaining the ability of LSECtin to facilitate infection by Ebola virus. High mannose glycans are also present on the viral glycoprotein, which explains why DC-SIGN also binds to this virus. Thus, multiple receptors interact with surface glycoproteins of enveloped viruses that bear different types of relatively poorly processed glycans.",,"['Powlesland, Alex S.', 'Fisch, Tanja', 'Taylor, Maureen E.', 'Smith, David F.', 'Tissot, Bérangère', 'Dell, Anne', 'Pöhlmann, Stefan', 'Drickamer, Kurt']",,,,
,PMC,Targeting Inflammatory Demyelinating Lesions to Sites of Wallerian Degeneration,http://dx.doi.org/10.2353/ajpath.2007.070147,PMC2043517,,,"In Theiler’s murine encephalomyelitis virus (TMEV) infection, an animal model for multiple sclerosis (MS), axonal injury precedes inflammatory demyelinating lesions, and the distribution of axonal damage present during the early phase of infection corresponds to regions where subsequent demyelination occurs during the chronic phase. We hypothesized that axonal damage recruits inflammatory cells to sites of Wallerian degeneration, leading to demyelination. Three weeks after TMEV infection, axonal degeneration was induced in the posterior funiculus of mice by injecting the toxic lectin Ricinus communis agglutinin (RCA) I into the sciatic nerve. Neuropathology was examined 1 week after lectin injection. Control mice, infected with TMEV but receiving no RCA I, had inflammatory demyelinating lesions in the anterior/lateral funiculi. Other control mice that received RCA I alone did not develop inflammatory lesions. In contrast, RCA I injection into TMEV-infected mice induced lesions in the posterior funiculus in addition to the anterior/lateral funiculi. We found no differences in lymphoproliferative responses or antibody titers against TMEV among the groups. This suggests that axonal degeneration contributes to the recruitment of inflammatory cells into the central nervous system by altering the local microenvironment. In this scenario, lesions develop from the axon (inside) to the myelin (outside) (Inside-Out model).",,"['Tsunoda, Ikuo', 'Tanaka, Tomoko', 'Saijoh, Yukio', 'Fujinami, Robert S.']",,,,
,PMC,"International Research Networks in Viral Structural Proteomics: again, lessons from SARS",http://dx.doi.org/10.1016/j.antiviral.2007.09.007,PMC2793675,,,"Emerging and re-emerging pathogens and bioterror threats require an organized and coherent response from the worldwide research community to maximize available resources and competencies with the primary goals to understand the pathogen and enable intervention. In 2001, the Structural Proteomics In Europe project prototyped the pan-viral structural genomic approach, and the SARS outbreak in 2003 accelerated the concept of structural characterization of all proteins from a viral proteome and the interaction with their host partners. Following that approach, in 2004 the center for Functional and Structural Proteomics for SARS-CoV related proteins was initiated as part of the US NIH NIAID proteomics resource centers. Across worldwide efforts in Asia, Europe and America, the international research teams working on SARS-CoV have now determined experimental structural information for 45% of the SARS-CoV proteins and 53% of all its soluble proteins. This data is fully available to the scientific community and is providing an unprecedented level of insight to this class of RNA viruses. The efforts and results by the international scientific community to the SARS outbreak are serving as an example and roadmap of a rapid response using modern research methods.",,"['Canard, Bruno', 'Joseph, Jeremiah S.', 'Kuhn, Peter']",,,,
,PMC,"Motivating action: Why should Canadian physicians participate in research, education, or patient care in the developing world?",,PMC2231457,,,,,"Singer, Peter A.",,,,
,PMC,"Contributing to communicable diseases intelligence management in Canada: CACMID meeting, March 2007, Halifax, Nova Scotia",,PMC2533573,,,"In the spring of 2003, the Public Health Agency of Canada (then, Health Canada) partnered with several provincial/territorial and regional public health stakeholders to improve pan-Canadian public health surveillance, communications and response through the application of new technologies. This resulted in the creation of the Canadian Network for Public Health Intelligence (CNPHI), a comprehensive framework of applications and resources designed to fill critical gaps in Canada's national public health infostructure. Over the past four years, the CNPHI has evolved into Canada's only pan-Canadian public health information management system. With over 2000 registered users, the current CNPHI environment consists of more than 30 integrated applications and systems that can be loosely categorized into four functional groups: data exchange; data analysis and integration; communication, collaboration and coordination; and knowledge management. Despite poor data repositories, legacy information management systems, and the lack of standards and agreements, the CNPHI has demonstrated that much can be accomplished in these areas. Over the next decade, significant barriers impeding additional advances will be bridged through the implementation of the Electronic Health Record, and through ongoing efforts to address gaps in standards, and data- and information-sharing agreements. Together with new technologies coming on-line, opportunities to further enhance public health surveillance and response will be limited only by one's imagination.",,"['Mukhi, Shamir', 'Aramini, Jeff', 'Kabani, Amin']",,,,
,PMC,Initial sequence and comparative analysis of the cat genome,http://dx.doi.org/10.1101/gr.6380007,PMC2045150,,,"The genome sequence (1.9-fold coverage) of an inbred Abyssinian domestic cat was assembled, mapped, and annotated with a comparative approach that involved cross-reference to annotated genome assemblies of six mammals (human, chimpanzee, mouse, rat, dog, and cow). The results resolved chromosomal positions for 663,480 contigs, 20,285 putative feline gene orthologs, and 133,499 conserved sequence blocks (CSBs). Additional annotated features include repetitive elements, endogenous retroviral sequences, nuclear mitochondrial (numt) sequences, micro-RNAs, and evolutionary breakpoints that suggest historic balancing of translocation and inversion incidences in distinct mammalian lineages. Large numbers of single nucleotide polymorphisms (SNPs), deletion insertion polymorphisms (DIPs), and short tandem repeats (STRs), suitable for linkage or association studies were characterized in the context of long stretches of chromosome homozygosity. In spite of the light coverage capturing ∼65% of euchromatin sequence from the cat genome, these comparative insights shed new light on the tempo and mode of gene/genome evolution in mammals, promise several research applications for the cat, and also illustrate that a comparative approach using more deeply covered mammals provides an informative, preliminary annotation of a light (1.9-fold) coverage mammal genome sequence.",,"['Pontius, Joan U.', 'Mullikin, James C.', 'Smith, Douglas R.', None, 'Lindblad-Toh, Kerstin', 'Gnerre, Sante', 'Clamp, Michele', 'Chang, Jean', 'Stephens, Robert', 'Neelam, Beena', 'Volfovsky, Natalia', 'Schäffer, Alejandro A.', 'Agarwala, Richa', 'Narfström, Kristina', 'Murphy, William J.', 'Giger, Urs', 'Roca, Alfred L.', 'Antunes, Agostinho', 'Menotti-Raymond, Marilyn', 'Yuhki, Naoya', 'Pecon-Slattery, Jill', 'Johnson, Warren E.', 'Bourque, Guillaume', 'Tesler, Glenn', None, 'O’Brien, Stephen J.']",,,,
,PMC,Forthcoming papers,http://dx.doi.org/10.1111/j.1365-2567.2007.02742.x,PMC2266018,,,,,,,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.02099-07,PMC2168985,,,,,,,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.01962-07,PMC2168791,,,,,,,,,
,PMC,SOURCES OF DATA FOR IMPROVED SURVEILLANCE OF HIV/AIDS IN CHINA,,PMC2730767,,,"The objective of this paper is to describe the evolution of human immunodeficiency virus/acquired immunodeficiency syndrome surveillance in mainland China, with a focus on reviewing the sources of data being used for improved surveillance of HIV/AIDS. We review the development of HIV/AIDS surveillance and its multiple data sources to monitor the dynamics of HIV/AIDS in China. The surveillance system for HIV/AIDS in China was initiated in 1986. It has evolved in three stages: (1) passive surveillance, (2) HIV sentinel surveillance with coexisting active surveillance and passive surveillance, and (3) comprehensive surveillance. In parallel with the evolution of the surveillance system itself, the HIV epidemic in China has gone through increasing stages of complexity, through an Introduction Phase, a Spreading Phase, and a Rapidy Spreading Phase. More reliable data from improved surveillance suggest that the HIV/AIDS epidemic is expanding in China. HIV infections among 2005 estimates remain concentrated among injection drug users (IDUs), those buying and selling sex, and men who have sex with men. Better HIV/AIDS surveillance synthesizes multiple data sources to provide a more accurate picture of the dynamics of specific HIV/AIDS circumstances in different areas of China. Improved surveillance is meaningful insofar as data are used to implement more effective HIV prevention programs in China. Support for surveillance and strategic analyses can enable policy decision makers to make more effective program choices and mobilize adequate resources to contain HIV.",,"['Jia, Yujiang', 'Lu, Fan', 'Sun, Xinhua', 'Vermund, Sten H']",,,,
,PMC,Evidence from Multiplex Molecular Assays for Complex Multipathogen Interactions in Acute Respiratory Infections,http://dx.doi.org/10.1128/JCM.01117-07,PMC2224244,,,"While most diagnostic processes cease with the detection of the first relevant infectious agent, newer multiplexed molecular methods which provide simultaneous analysis of multiple agents may give a more accurate representation of the true pathogen spectrum in these samples. To examine this in the context of respiratory infections, acute-phase respiratory specimens submitted to our clinical diagnostic microbiology/virology laboratory for our routine VIRAP diagnosis protocol during the spring 2006 peak respiratory infection season were processed in parallel by analysis with Genaco (QiaPlex) ResPlex I and ResPlex II molecular diagnostic panels. A total of 1,742 specimens were examined for 21 relevant targets each. The resulting data reveal that multiple infections are frequent and provide evidence for complex interactions between different infectious agents. Statistically relevant association patterns (both positive and negative) were observed between particular pathogens. While some interactions we observed are substantiated by prior reports in the literature, several specific patterns do not appear to have been reported previously. In addition, we report preliminary clinical evidence which supports a hypothesis that these coinfections are medically relevant and that effective treatment for severe respiratory tract infections will increasingly require diagnosis of all involved pathogens, as opposed to single-pathogen reporting.",,"['Brunstein, John D.', 'Cline, Christy L.', 'McKinney, Steven', 'Thomas, Eva']",,,,
,PMC,Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning,http://dx.doi.org/10.1016/j.jim.2007.09.017,PMC2243222,,,"We have developed an efficient strategy that combines immunoglobulin (Ig) gene repertoire analysis and Ig reactivity profiling at the single cell level. Based on surface marker expression individual cells at different stages of human B cell development are isolated by fluorescence-activated cell sorting. For each cell Ig heavy and corresponding Ig light chain gene transcripts are amplified by nested RT-PCR and cloned into eukaryotic expression vectors to produce monoclonal human antibodies of the same specificity in vitro. All reactions are performed in 96-well plates and allow cloning of large numbers of Ig genes. The recombinant antibodies are tested for reactivity with diverse self-and non-self antigens and the reactivity profile can be directly linked to the complete Ig heavy and IgL chain gene sequence information that is obtained as part of the cloning strategy. In summary, our method to clone and express human monoclonal antibodies is unbiased, highly efficient, requires only small cell numbers and the recombinant antibodies allow direct conclusions on the frequency of specific human B cells in a diverse repertoire.",,"['Tiller, Thomas', 'Meffre, Eric', 'Yurasov, Sergey', 'Tsuiji, Makoto', 'Nussenzweig, Michel C.', 'Wardemann, Hedda']",,,,
,PMC,Inhibition of retinoic acid-induced skin irritation in calorie-restricted mice,http://dx.doi.org/10.1007/s00403-007-0797-y,PMC5644022,,,"Mice on a calorie-restricted (CR) diet (total calories restricted to 70% of ad libitum; AL) for periods of time ranging from 3 to 18 months were examined for response to topical treatment with all-trans retinoic acid (RA). Daily application of a 0.1% solution of RA to the shaved skin of UM-HET3 mice on an AL diet produced a severe irritation that was evident by day 4, maximal at day 7–8 and still detectable at day 14. Skin irritation was characterized by redness, dryness, flaking and failure of the hair to grow at the treated site. In CR mice, the same treatment produced little detectable irritation. Animals were sacrificed at the end of the retinoid-treatment period (day 7 or day 14) and skin from these animals was examined histologically. In both AL and CR mice, a similar degree of epidermal hyperplasia was observed. Numerous inflammatory cells (mononuclear cells and granulocytes) were present in the skin of both groups. Occasional S100-positive cells (presumably Langerhans cells) were also observed in the epidermis of skin from both groups. S100-positive cells were also observed in the dermis. When skin from CR and AL mice was incubated in organ culture for 3 days (on day 7 after initiation of RA treatment), similar levels of four different pro-inflammatory cytokines were found in the conditioned medium. Soluble type I collagen levels were also similar. In contrast, the level of matrix metalloproteinase-9 was lower in the conditioned medium of skin from CR mice than in conditioned medium from skin cultures of AL mice. Taken together, these studies suggest that CR may provide a way to mitigate the irritation that normally accompanies RA treatment without compromising the beneficial effects of retinoid use. CR appears to exert a protective effect at the target tissue level rather than by a reduction in pro-inflammatory events, per se.",,"['Varani, James', 'Bhagavathula, Narasimharao', 'Aslam, Muhammad Nadeem', 'Fay, Kevin', 'Warner, Roscoe L.', 'Hanosh, Andrew', 'Barron, Adam G.', 'Miller, Richard A.']",,,,
,PMC,5′-Fluoro-5′-deoxyaristeromycin,http://dx.doi.org/10.1016/j.bmcl.2007.10.095,PMC2692407,,,"5′-Fluoro-5′-deoxyaristeromycin (2) has been prepared via a Mitsunobu coupling of (1S,2S,3R,4S)-2,3-(cyclopentylidenedioxy)-4-fluoromethylcyclopentan-1-ol with N6-bis-boc protected adenine. This procedure is adaptable to preparing a number of 5′-fluoro-5′-deoxycarbocyclic nucleoside analogs with diversity in the heterocyclic base. Antiviral analysis found promising activity for 2 towards measles but no other viruses. No cytotoxicity was observed for 2.",,"['Li, Weikuan', 'Yin, Xueqiang', 'Schneller, Stewart W.']",,,,
,PMC,New Pre-pandemic Influenza Vaccines: An Egg-and Adjuvant-independent Human Adenoviral Vector Strategy Induces Long-lasting Protective Immune Responses in Mice,http://dx.doi.org/10.1038/sj.clpt.6100418,PMC2793094,,,"Highly pathogenic avian H5N1 influenza viruses that are currently circulating in southeast Asia may acquire the potential to cause the next influenza pandemic. A number of alternate approaches are being pursued to generate cross-protective, dose-sparing, safe, and effective vaccines, as traditional vaccine approaches, i.e., embryonated egg-grown, are not immunogenic. We developed a replication-incompetent adenoviral vector-based, adjuvant-and egg-independent pandemic influenza vaccine strategy as a potential alternative to conventional egg-derived vaccines. In this paper, we address suboptimal dose and longevity of vaccine-induced protective immunity and demonstrate that a vaccine dose as little as 1 × 10(6) plaque-forming unit (PFU) is sufficient to induce protective immune responses against a highly pathogenic H5N1 virus. Furthermore, the vaccine-induced humoral and cellular immune responses and protective immunity persisted at least for a year.",,"['Hoelscher, MA', 'Jayashankar, L', 'Garg, S', 'Veguilla, V', 'XLu', 'Singh, N', 'Katz, JM', 'Mittal, SK', 'Sambhara, S']",,,,
,PMC,Intracellular Restriction of a Productive Noncytopathic Coronavirus Infection,http://dx.doi.org/10.1128/JVI.01251-07,PMC2224397,,,"Virus infection in vitro can either result in a cytopathic effect (CPE) or proceed without visible changes in infected cells (noncytopathic infection). We are interested in understanding the mechanisms controlling the impact of coronavirus infection on host cells. To this end, we compared a productive, noncytopathic infection of murine hepatitis virus (MHV) strain A59 in the fibroblastlike cell line NIH 3T3 with cytopathic MHV infections. Infected NIH 3T3 cells could be cultured for up to 4 weeks without apparent CPE and yet produce virus at 10(7) to 10(8) PFU/ml. Using flow cytometry, we demonstrated that NIH 3T3 cells expressed as much MHV receptor CEACAM1 as other cell lines which die from MHV infection. In contrast, using quantitative reverse transcription-PCR and metabolic labeling of RNA, we found that the rate of viral RNA amplification in NIH 3T3 cells was lower than the rate in cells in which MHV induces a CPE. The rate of cellular RNA synthesis in contact-inhibited confluent NIH 3T3 cells was also lower than in cells permissive to cytopathic MHV infection. However, the induction of cellular RNA synthesis in growing NIH 3T3 cells did not result in an increase of either viral RNA amplification or CPE. Our results suggest that a specific, receptor CEACAM1-independent mechanism restricting coronaviral RNA synthesis and CPE is present in NIH 3T3 and, possibly, other cells with preserved contact inhibition.",,"['Slobodskaya, Olga', 'Laarman, Alexander', 'Spaan, Willy J. M.']",,,,
,PMC,Suppression of Acute Anti-Friend Virus CD8(+) T-Cell Responses by Coinfection with Lactate Dehydrogenase-Elevating Virus,http://dx.doi.org/10.1128/JVI.01413-07,PMC2224392,,,"Friend virus (FV) and lactate dehydrogenase-elevating virus (LDV) are endemic mouse viruses that can cause long-term chronic infections in mice. We found that numerous mouse-passaged FV isolates also contained LDV and that coinfection with LDV delayed FV-specific CD8(+) T-cell responses during acute infection. While LDV did not alter the type of acute pathology induced by FV, which was severe splenomegaly caused by erythroproliferation, the immunosuppression mediated by LDV increased both the severity and the duration of FV infection. Compared to mice infected with FV alone, those coinfected with both FV and LDV had delayed CD8(+) T-cell responses, as measured by FV-specific tetramers. This delayed response accounted for the prolonged and exacerbated acute phase of FV infection. Suppression of FV-specific CD8(+) T-cell responses occurred not only in mice infected concomitantly with LDV but also in mice chronically infected with LDV 8 weeks prior to infection with FV. The LDV-induced suppression was not mediated by T regulatory cells, and no inhibition of the CD4(+) T-cell or antibody responses was observed. Considering that most human adults are carriers of chronically infectious viruses at the time of new virus insults and that coinfections with viruses such as human immunodeficiency virus and hepatitis C virus are currently epidemic, it is of great interest to determine how infection with one virus may impact host responses to a second infection. Coinfection of mice with LDV and FV provides a well-defined, natural host model for such studies.",,"['Robertson, Shelly J.', 'Ammann, Christoph G.', 'Messer, Ronald J.', 'Carmody, Aaron B.', 'Myers, Lara', 'Dittmer, Ulf', 'Nair, Savita', 'Gerlach, Nicole', 'Evans, Leonard H.', 'Cafruny, William A.', 'Hasenkrug, Kim J.']",,,,
,PMC,Reovirus Apoptosis and Virulence Are Regulated by Host Cell Membrane Penetration Efficiency,http://dx.doi.org/10.1128/JVI.01739-07,PMC2224352,,,"Apoptosis plays an important role in the pathogenesis of reovirus encephalitis and myocarditis in infected animals. Differences in apoptosis efficiency displayed by reovirus strains are linked to the viral μ1-encoding M2 gene segment. Studies using pharmacologic inhibitors of reovirus replication demonstrate that apoptosis induction by reovirus requires viral disassembly in cellular endosomes but not RNA synthesis. Since the μ1 protein functions to pierce endosomal membranes during this temporal window, these findings point to an important role for μ1 in activating signaling pathways that lead to apoptosis. To understand mechanisms used by μ1 to induce apoptosis, a panel of μ1 mutant viruses generated by reverse genetics was analyzed for the capacities to penetrate host cell membranes, activate proapoptotic signaling pathways, evoke cell death, and produce encephalitis in newborn mice. We found that single amino acid changes within the δ region of μ1 reduce the efficiency of membrane penetration. These mutations also diminish the capacities of reovirus to activate proapoptotic transcription factors NF-κB and IRF-3 and elicit apoptosis. Additionally, we observed that following intracranial inoculation, an apoptosis-deficient μ1 mutant is less virulent in newborn mice in comparison to the wild-type virus. These results indicate a critical function for the membrane penetration activity of μ1 in evoking prodeath signaling pathways that regulate reovirus pathogenesis.",,"['Danthi, Pranav', 'Kobayashi, Takeshi', 'Holm, Geoffrey H.', 'Hansberger, Mark W.', 'Abel, Ty W.', 'Dermody, Terence S.']",,,,
,PMC,Preparation of Benzalkonium Salts Differing in the Length of a Side Alkyl Chain,http://dx.doi.org/10.3390/12102341,PMC6149131,,,"Benzalkonium salts are widely used as disinfectants, biocides and detergents, among a variety of other applications. The cationic surface-activity of these salts determines their potential to act as a biocide on both target and non-target organisms. In this study, a quick synthesis of a complete set of the benzalkonium salts differing in the length of an alkylating chain (from C(2) to C(20)) is described. Moreover, their (1)H-NMR, HPLC-MS, TLC and HPLC analysis were recorded.",,"['Kuca, Kamil', 'Marek, Jan', 'Stodulka, Petr', 'Musilek, Kamil', 'Hanusova, Petra', 'Hrabinova, Martina', 'Jun, Daniel']",,,,
,PMC,Immunogenicity and Protection Efficacy of Subunit-based Smallpox Vaccines Using Variola Major Antigens,http://dx.doi.org/10.1016/j.virol.2007.09.029,PMC2254135,,,"The viral strain responsible for smallpox infection is variola major (VARV). As a result of the successful eradication of smallpox with the vaccinia virus (VACV), the general population is no longer required to receive a smallpox vaccine, and will have no protection against smallpox. This lack of immunity is a concern due to the potential for use of smallpox as a biological weapon. Considerable progress has been made in the development of subunit-based smallpox vaccines resulting from the identification of VACV protective antigens. It also offers the possibility of using antigens from VARV to formulate the next generation subunit-based smallpox vaccines. Here, we show that codon-optimized DNA vaccines expressing three VARV antigens (A30, B7 and F8) and their recombinant protein counterparts elicited high-titer, cross-reactive, VACV neutralizing antibody responses in mice. Vaccinated mice were protected from intraperitoneal and intranasal challenges with VACV. These results suggest the feasibility of a subunit smallpox vaccine based on the VARV antigen sequences to induce immunity against poxvirus infection.",,"['Sakhatskyy, Pavlo', 'Wang, Shixia', 'Zhang, Chuanyou', 'Chou, Te-Hui', 'Kishko, Michael', 'Lu, Shan']",,,,
,PMC,The health of the public is the foundation of prosperity: the work of the Public Health Agency of Canada at home and around the world,http://dx.doi.org/10.1503/cmaj.071301,PMC2025636,,,,,"MD MHSc, David Butler-Jones",,,,
,PMC,RNA interference and antiviral therapy,http://dx.doi.org/10.3748/wjg.v13.i39.5169,PMC4171298,,,"RNA interference (RNAi) is an evolutionally conserved gene silencing mechanism present in a variety of eukaryotic species. RNAi uses short double-stranded RNA (dsRNA) to trigger degradation or translation repression of homologous RNA targets in a sequence-specific manner. This system can be induced effectively in vitro and in vivo by direct application of small interfering RNAs (siRNAs), or by expression of short hairpin RNA (shRNA) with non-viral and viral vectors. To date, RNAi has been extensively used as a novel and effective tool for functional genomic studies, and has displayed great potential in treating human diseases, including human genetic and acquired disorders such as cancer and viral infections. In the present review, we focus on the recent development in the use of RNAi in the prevention and treatment of viral infections. The mechanisms, strategies, hurdles and prospects of employing RNAi in the pharmaceutical industry are also discussed.",,"['Ma, Yan', 'Chan, Chu-Yan', 'He, Ming-Liang']",,,,
,PMC,Detection and Typing of Human Herpesvirus 6 by Molecular Methods in Specimens from Patients Diagnosed with Encephalitis or Meningitis,http://dx.doi.org/10.1128/JCM.01692-07,PMC2168559,,,"Human herpesvirus 6 (HHV-6) was detected in specimens from patients hospitalized with symptoms of encephalitis or meningitis. A real-time PCR assay was developed which has a linear dynamic range of 5 to 5 × 10(6) copies of HHV-6 and a sensitivity of five gene copies per reaction. While the assay detects both subtypes, HHV-6A and HHV-6B, it is specific and does not cross-react with a selected specificity panel. A total of 1,482 patient specimens, which were collected between 2003 and 2007, were tested; 26 specimens from 24 patients were found to be positive for HHV-6 by real-time PCR. The HHV-6 detection rate in this population was therefore 1.75%. The majority of the specimens tested (>95%) were cerebrospinal fluid (CSF) specimens. We were able to type 20 of the 26 positive specimens by conventional PCR and sequence analysis; all were HHV-6B. Forty-two percent of the patients were 3 years of age or younger, which may indicate a primary infection in these patients. Given the ages of the remaining patients (from 4 to 81 years), their infections were most probably due to virus reactivations. Where information was available, symptoms of patients included fever (71%), altered mental status (67%), and abnormal CSF profile (75%). Fifty percent of patients of 3 years of age or younger suffered from seizures. The detection of HHV-6 in specimens from patients diagnosed with encephalitis or meningitis, in the absence of a positive PCR result for other agents, strongly suggests a role for HHV-6 in the pathogenesis of these central nervous system diseases.",,"['Tavakoli, Norma P.', 'Nattanmai, Seela', 'Hull, Rene', 'Fusco, Heather', 'Dzigua, Lela', 'Wang, Heng', 'Dupuis, Michelle']",,,,
,PMC,Heptad Repeat-Derived Peptides Block Protease-Mediated Direct Entry from the Cell Surface of Severe Acute Respiratory Syndrome Coronavirus but Not Entry via the Endosomal Pathway,http://dx.doi.org/10.1128/JVI.01697-07,PMC2224400,,,"The peptides derived from the heptad repeat (HRP) of severe acute respiratory syndrome coronavirus (SCoV) spike protein (sHRPs) are known to inhibit SCoV infection, yet their efficacies are fairly low. Recently our research showed that some proteases facilitated SCoV's direct entry from the cell surface, resulting in a more efficient infection than the previously known infection via endosomal entry. To compare the inhibitory effect of the sHRP in each pathway, we selected two sHRPs, which showed a strong inhibitory effect on the interaction of two heptad repeats in a rapid and virus-free in vitro assay system. We found that they efficiently inhibited SCoV infection of the protease-mediated cell surface pathway but had little effect on the endosomal pathway. This finding suggests that sHRPs may effectively prevent infection in the lungs, where SCoV infection could be enhanced by proteases produced in this organ. This is the first observation that HRP exhibits different effects on virus that takes the endosomal pathway and virus that enters directly from the cell surface.",,"['Ujike, Makoto', 'Nishikawa, Hiroki', 'Otaka, Akira', 'Yamamoto, Naoki', 'Yamamoto, Norio', 'Matsuoka, Masao', 'Kodama, Eiichi', 'Fujii, Nobutaka', 'Taguchi, Fumihiro']",,,,
,PMC,A Highly Divergent Picornavirus in a Marine Mammal,http://dx.doi.org/10.1128/JVI.01240-07,PMC2224395,,,"Nucleic acids from an unidentified virus from ringed seals (Phoca hispida) were amplified using sequence-independent PCR, subcloned, and then sequenced. The full genome of a novel RNA virus was derived, identifying the first sequence-confirmed picornavirus in a marine mammal. The phylogenetic position of the tentatively named seal picornavirus 1 (SePV-1) as an outlier to the grouping of parechoviruses was found consistently in alignable regions of the genome. A mean protein sequence identity of only 19.3 to 30.0% was found between the 3D polymerase gene sequence of SePV-1 and those of other picornaviruses. The predicted secondary structure of the short 506-base 5′-untranslated region showed some attributes of a type IVB internal ribosome entry site, and the polyprotein lacked an apparent L peptide, both properties associated with the Parechovirus genus. The presence of two SePV-1 2A genes and of the canonical sequence required for cotranslational cleavage resembled the genetic organization of Ljungan virus. Minor genetic variants were detected in culture supernatants derived from 8 of 108 (7.4%) seals collected in 2000 to 2002, indicating a high prevalence of SePV-1 in this hunted seal population. The high level of genetic divergence of SePV-1 compared to other picornaviruses and its mix of characteristics relative to its closest relatives support the provisional classification of SePV-1 as the prototype for a new genus in the family Picornaviridae.",,"['Kapoor, A.', 'Victoria, J.', 'Simmonds, P.', 'Wang, C.', 'Shafer, R. W.', 'Nims, R.', 'Nielsen, O.', 'Delwart, E.']",,,,
,PMC,Attenuation of Recombinant Vesicular Stomatitis Virus-Human Immunodeficiency Virus Type 1 Vaccine Vectors by Gene Translocations and G Gene Truncation Reduces Neurovirulence and Enhances Immunogenicity in Mice,http://dx.doi.org/10.1128/JVI.01515-07,PMC2224363,,,"Recombinant vesicular stomatitis virus (rVSV) has shown great potential as a new viral vector for vaccination. However, the prototypic rVSV vector described previously was found to be insufficiently attenuated for clinical evaluation when assessed for neurovirulence in nonhuman primates. Here, we describe the attenuation, neurovirulence, and immunogenicity of rVSV vectors expressing human immunodeficiency virus type 1 Gag. These rVSV vectors were attenuated by combinations of the following manipulations: N gene translocations (N4), G gene truncations (CT1 or CT9), noncytopathic M gene mutations (Mncp), and positioning of the gag gene into the first position of the viral genome (gag1). The resulting N4CT1-gag1, N4CT9-gag1, and MncpCT1-gag1 vectors demonstrated dramatically reduced neurovirulence in mice following direct intracranial inoculation. Surprisingly, in spite of a very high level of attenuation, the N4CT1-gag1 and N4CT9-gag1 vectors generated robust Gag-specific immune responses following intramuscular immunization that were equivalent to or greater than immune responses generated by the more virulent prototypic vectors. MncpCT1-gag1 also induced Gag-specific immune responses following intramuscular immunization that were equivalent to immune responses generated by the prototypic rVSV vector. Placement of the gag gene in the first position of the VSV genome was associated with increased in vitro expression of Gag protein, in vivo expression of Gag mRNA, and enhanced immunogenicity of the vector. These findings demonstrate that through directed manipulation of the rVSV genome, vectors that have reduced neurovirulence and enhanced immunogenicity can be made.",,"['Cooper, David', 'Wright, Kevin J.', 'Calderon, Priscilla C.', 'Guo, Min', 'Nasar, Farooq', 'Johnson, J. Erik', 'Coleman, John W.', 'Lee, Margaret', 'Kotash, Cheryl', 'Yurgelonis, Irene', 'Natuk, Robert J.', 'Hendry, R. Michael', 'Udem, Stephen A.', 'Clarke, David K.']",,,,
,PMC,Altered Pathogenesis of Porcine Respiratory Coronavirus in Pigs due to Immunosuppressive Effects of Dexamethasone: Implications for Corticosteroid Use in Treatment of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.01702-07,PMC2168842,,,"The pathogenesis and optimal treatments for severe acute respiratory syndrome (SARS) are unclear, although corticosteroids were used to reduce lung and systemic inflammation. Because the pulmonary pathology of porcine respiratory coronavirus (PRCV) in pigs resembles SARS, we used PRCV as a model to clarify the effects of the corticosteroid dexamethasone (DEX) on coronavirus (CoV)-induced pneumonia. Conventional weaned pigs (n = 130) in one of four groups (PRCV/phosphate-buffered saline [PBS] [n = 41], PRCV/DEX [n = 41], mock/PBS [n = 23], and mock/DEX [n = 25]) were inoculated intranasally and intratracheally with the ISU-1 strain of PRCV (1 × 10(7) PFU) or cell culture medium. DEX was administered (once daily, 2 mg/kg of body weight/day, intramuscularly) from postinoculation day (PID) 1 to 6. In PRCV/DEX pigs, significantly milder pneumonia, fewer PRCV-positive cells, and lower viral RNA titers were present in lungs early at PID 2; however, at PID 4, 10, and 21, severe bronchointerstitial pneumonia, significantly higher numbers of PRCV-positive cells, and higher viral RNA titers were observed compared to results for PRCV/PBS pigs. Significantly lower numbers of CD2(+), CD3(+), CD4(+), and CD8(+) T cells were also observed in lungs of PRCV/DEX pigs than in those of PRCV/PBS pigs at PID 8 and 10, coincident with fewer gamma interferon (IFN-γ)-secreting cells in the tracheobronchial lymph nodes as determined by enzyme-linked immunospot assay. Our results confirm that DEX treatment alleviates PRCV pneumonia early (PID 2) in the infection but continued use through PID 6 exacerbates later stages of infection (PID 4, 10, and 21), possibly by decreasing cellular immune responses in the lungs (IFN-γ-secreting T cells), thereby creating an environment for more-extensive viral replication. These data have potential implications for corticosteroid use with SARS-CoV patients and suggest a precaution against prolonged use based on their unproven efficacy in humans, including possible detrimental secondary effects.",,"['Jung, Kwonil', 'Alekseev, Konstantin P.', 'Zhang, Xinsheng', 'Cheon, Doo-Sung', 'Vlasova, Anastasia N.', 'Saif, Linda J.']",,,,
,PMC,Oct4 expression is not required for mouse somatic stem cell self-renewal,http://dx.doi.org/10.1016/j.stem.2007.07.020,PMC2151746,,,"The Pou domain containing transcription factor Oct4 is a well-established regulator of pluripotency in the inner cell mass of the mammalian blastocyst as well as in embryonic stem cells. While it has been shown that the Oct4 gene is inactivated through a series of epigenetic modifications following implantation, recent studies have detected Oct4 activity in a variety of somatic stem cells and tumor cells. Based on these observations it has been suggested that Oct4 may also function in maintaining self-renewal of somatic stem cells and, in addition, may promote tumor formation. We employed a genetic approach to determine whether Oct4 is important for maintaining pluripotency in the stem cell compartments of several somatic tissues including the intestinal epithelium, bone marrow (hematopoietic and mesenchymal lineages), hair follicle, brain, and liver. Oct4 gene ablation in these tissues revealed no abnormalities in homeostasis or regenerative capacity. We conclude that Oct4 is dispensable for both self-renewal and maintenance of somatic stem cells in the adult mammal.",,"['Lengner, Christopher J', 'Camargo, Fernando D', 'Hochedlinger, Konrad', 'Welstead, G Grant', 'Zaidi, Samir', 'Gokhale, Sumita', 'Scholer, Hans R', 'Tomilin, Alexey', 'Jaenisch, Rudolf']",,,,
,PMC,Functional analysis of Leishmania major cyclophilin,http://dx.doi.org/10.1016/j.ijpara.2007.10.001,PMC2377454,,,"A potent immunosuppressive drug cyclosporin A (CsA) is known to inhibit human cell infection by the pathogenic protozoan parasite Leishmania major both in vitro and in vivo. The proposed mechanism of action involves CsA binding to Leishmania major-expressed cyclophilin and subsequent down-regulation of signaling events necessary for establishing productive infection. Recently, we identified a ubiquitously expressed membrane protein, CD147, as a signaling receptor for extracellular cyclophilins in mammalian cells. Here we demonstrate that, while being enzymatically active, the Leishmania cyclophilin, unlike its human homologue, does not interact with CD147 on the cell surface of target cells. CD147 facilitates neither Leishmania binding nor infection. Primary structure and biochemical analyses revealed that the parasite’s cyclophilin is defective in heparan binding, an event required for signaling interaction between CD147 and human cyclophilin. When the heparan-binding motif was reconstituted in Leishmania cyclophilin, it regained the CD147-dependent signaling activity. These results underscore a critical role of cyclophilin-heparan interactions in CD147-mediated signaling events and argue against the role of Leishmania cyclophilin in parasite binding to target cells.",,"['Yurchenko, Vyacheslav', 'Xue, Zhu', 'Sherry, Barbara', 'Bukrinsky, Michael']",,,,
,PMC,Type I Interferons Are Essential in Controlling Neurotropic Coronavirus Infection Irrespective of Functional CD8 T Cells,http://dx.doi.org/10.1128/JVI.01794-07,PMC2224360,,,"Neurotropic coronavirus infection induces expression of both beta interferon (IFN-β) RNA and protein in the infected rodent central nervous system (CNS). However, the relative contributions of type I IFN (IFN-I) to direct, cell-type-specific virus control or CD8 T-cell-mediated effectors in the CNS are unclear. IFN-I receptor-deficient (IFNAR(−/−)) mice infected with a sublethal and demyelinating neurotropic virus variant and those infected with a nonpathogenic neurotropic virus variant both succumbed to infection within 9 days. Compared to wild-type (wt) mice, replication was prominently increased in all glial cell types and spread to neurons, demonstrating expanded cell tropism. Furthermore, increased pathogenesis was associated with significantly enhanced accumulation of neutrophils, tumor necrosis factor alpha, interleukin-6, chemokine (C-C motif) ligand 2, and IFN-γ within the CNS. The absence of IFN-I signaling did not impair induction or recruitment of virus-specific CD8 T cells, the primary adaptive mediators of virus clearance in wt mice. Despite similar IFN-γ-mediated major histocompatibility complex class II upregulation on microglia in infected IFNAR(−/−) mice, class I expression was reduced compared to that on microglia in wt mice, suggesting a synergistic role of IFN-I and IFN-γ in optimizing class I antigen presentation. These data demonstrate a critical direct antiviral role of IFN-I in controlling virus dissemination within the CNS, even in the presence of potent cellular immune responses. By limiting early viral replication and tropism, IFN-I controls the balance of viral replication and immune control in favor of CD8 T-cell-mediated protective functions.",,"['Ireland, Derek D. C.', 'Stohlman, Stephen A.', 'Hinton, David R.', 'Atkinson, Roscoe', 'Bergmann, Cornelia C.']",,,,
,PMC,Proteolysis of the Ebola Virus Glycoproteins Enhances Virus Binding and Infectivity,http://dx.doi.org/10.1128/JVI.01170-07,PMC2168880,,,"Cellular cathepsins are required for Ebola virus infection and are believed to proteolytically process the Ebola virus glycoprotein (GP) during entry. However, the significance of cathepsin cleavage during infection remains unclear. Here we demonstrate a role for cathepsin L (CatL) cleavage of Ebola virus GP in the generation of a stable 18-kDa GP1 viral intermediate that exhibits increased binding to and infectivity for susceptible cell targets. Cell binding to a lymphocyte line was increased when CatL-proteolysed pseudovirions were used, but lymphocytes remained resistant to Ebola virus GP-mediated infection. Genetic removal of the highly glycosylated mucin domain in Ebola virus GP resulted in cell binding similar to that observed with CatL-treated full-length GP, and no overall enhancement of binding or infectivity was observed when mucin-deleted virions were treated with CatL. These results suggest that cathepsin cleavage of Ebola virus GP facilitates an interaction with a cellular receptor(s) and that removal of the mucin domain may facilitate receptor binding. The influence of CatL in Ebola virus GP receptor binding should be useful in future studies characterizing the mechanism of Ebola virus entry.",,"['Kaletsky, Rachel L.', 'Simmons, Graham', 'Bates, Paul']",,,,
,PMC,The 29-Nucleotide Deletion Present in Human but Not in Animal Severe Acute Respiratory Syndrome Coronaviruses Disrupts the Functional Expression of Open Reading Frame 8,http://dx.doi.org/10.1128/JVI.01631-07,PMC2168875,,,"One of the most striking and dramatic genomic changes observed in the severe acute respiratory syndrome coronavirus (SARS-CoV) isolated from humans soon after its zoonotic transmission from palm civets was the acquisition of a characteristic 29-nucleotide deletion. This occurred in open reading frame 8 (ORF8), one of the accessory genes unique to the SARS-CoV. The function of ORF8 and the significance of the deletion are unknown. The intact ORF8 present in animal and some early human isolates encodes a 122-amino-acid polypeptide (8ab(+)), which we expressed in cells using the vaccinia virus T7 expression system. It was found to contain a cleavable signal sequence, which directs the precursor to the endoplasmic reticulum (ER) and mediates its translocation into the lumen. The cleaved protein became N-glycosylated, assembled into disulfide-linked homomultimeric complexes, and remained stably in the ER. The 29-nucleotide deletion splits ORF8 into two ORFs, 8a and 8b, encoding 39- and 84-residue polypeptides. The 8a polypeptide is likely to remain in the cytoplasm, as it is too small for its signal sequence to function and will therefore be directly released from the ribosome. However, we could not confirm this experimentally due to the lack of proper antibodies. ORF8b appeared not to be expressed in SARS-CoV-infected cells or when expressed from mRNA's mimicking mRNA8. This was due to the context of the internal AUG initiation codon, as we demonstrated after placing the ORF8b immediately behind the T7 promoter. A soluble, unmodified and monomeric 8b protein was now expressed in the cytoplasm, which was highly unstable and rapidly degraded. Clearly, the 29-nucleotide deletion disrupts the proper expression of the SARS-CoV ORF8, the implications of which are discussed.",,"['Oostra, Monique', 'de Haan, Cornelis A. M.', 'Rottier, Peter J. M.']",,,,
,PMC,Identification of Novel Antipoxviral Agents: Mitoxantrone Inhibits Vaccinia Virus Replication by Blocking Virion Assembly,http://dx.doi.org/10.1128/JVI.00770-07,PMC2168821,,,"The bioterror threat of a smallpox outbreak in an unvaccinated population has mobilized efforts to develop new antipoxviral agents. By screening a library of known drugs, we identified 13 compounds that inhibited vaccinia virus replication at noncytotoxic doses. The anticancer drug mitoxantrone is unique among the inhibitors identified in that it has no apparent impact on viral gene expression. Rather, it blocks processing of viral structural proteins and assembly of mature progeny virions. The isolation of mitoxantrone-resistant vaccinia strains underscores that a viral protein is the likely target of the drug. Whole-genome sequencing of mitoxantrone-resistant viruses pinpointed missense mutations in the N-terminal domain of vaccinia DNA ligase. Despite its favorable activity in cell culture, mitoxantrone administered intraperitoneally at the maximum tolerated dose failed to protect mice against a lethal intranasal infection with vaccinia virus.",,"['Deng, Liang', 'Dai, Peihong', 'Ciro, Anthony', 'Smee, Donald F.', 'Djaballah, Hakim', 'Shuman, Stewart']",,,,
,PMC,Lactic acid bacterial colonization and human rotavirus infection influence distribution and frequencies of monocytes/macrophages and dendritic cells in neonatal gnotobiotic pigs,http://dx.doi.org/10.1016/j.vetimm.2007.10.001,PMC2268605,,,"Despite accumulating knowledge of porcine macrophages and dendritic cells (DCs) from in vitro studies, information regarding monocytes/macrophages and DCs in lymphoid tissues of enteric pathogen-infected neonatal animals in vivo is limited. In this study we evaluated the influence of commensal bacterial [two strains of lactic acid bacteria (LAB), Lactobacillus acidophilus and L. reuteri] colonization and rotavirus infection on distribution and frequencies of monocytes/macrophages and conventional DCs (cDCs) in ileum, spleen and blood. Gnotobiotic pigs were inoculated with LAB and virulent Wa strain human rotavirus (HRV) (LAB+HRV+), HRV only (LAB−HRV+), LAB only (LAB+HRV−) or mock (LAB−HRV−). The cDCs were characterized as SWC3(+)CD11R1(+), whereas monocytes/macrophages were identified as SWC3(+)CD11R1(−) by flow cytometry in the gnotobiotic pigs at 10 days of age. Infection with HRV alone activated/recruited significantly more monocytes/macrophages to the intestine than LAB colonization and 56% versus 28% of these cells expressed CD14. Colonization with LAB alone also significantly increased the frequencies of monocytes/macrophages and cDCs and the CD14 expression on monocytes/macrophages in ileum and spleen compared to the controls. LAB colonization plus HRV infection significantly reduced macrophage and cDC frequencies in spleen compared to LAB colonization or HRV infection alone, suggesting that LAB colonization down-regulated HRV− infection-induced monocyte/macrophage activation/recruitment at the systemic lymphoid tissue. These results illustrated the distribution of porcine monocytes/macrophages and cDCs and the frequencies of CD14 expression on these cells in intestinal and systemic lymphoid tissues in the early stage of immune responses to intestinal colonization by LAB versus infection by an enteric pathogen HRV and will facilitate further in vivo studies on functional characterization of these immune cells in neonates.",,"['Zhang, Wei', 'Wen, Ke', 'Azevedo, Marli S.P.', 'Gonzalez, Ana', 'Saif, Linda J.', 'Li, Guohua', 'Yousef, Ahmed E.', 'Yuan, Lijuan']",,,,
,PMC,A human norovirus-like particle vaccine adjuvanted with ISCOM or mLT induces cytokine and antibody responses and protection to the homologous GII.4 human norovirus in a gnotobiotic pig disease model,http://dx.doi.org/10.1016/j.vaccine.2007.09.040,PMC4094375,,,"We inoculated gnotobiotic pigs oraly/intranasally with human norovirus GII.4 HS66 strain virus-like particles (VLP) and immunostimulating complexes (ISCOM) or mutant E. coli LT toxin (mLT, R192G) as mucosal adjuvants, then assessed intestinal and systemic antibody and cytokine responses and homologous protection. Both vaccines induced high rates of seroconversion (100%) and coproconversion (75–100%). The VLP+mLT vaccine induced Th1/Th2 serum cytokines and cytokine secreting cells, whereas the VLP+ISCOM vaccine induced Th2 biased responses with significantly elevated IgM, IgA and IgG antibody-secreting cells in intestine. Nevertheless, both vaccines induced increased protection rates against viral shedding and diarrhea (75–100%) compared to controls; however, only 57% of controls shed virus.",,"['Souza, Menira', 'Costantini, Veronica', 'Azevedo, Marli S. P', 'Saif, Linda J.']",,,,
,PMC,Quantifying social distancing arising from pandemic influenza,http://dx.doi.org/10.1098/rsif.2007.1197,PMC3226987,,,"Local epidemic curves during the 1918–1919 influenza pandemic were often characterized by multiple epidemic waves. Identifying the underlying cause(s) of such waves may help manage future pandemics. We investigate the hypothesis that these waves were caused by people avoiding potentially infectious contacts—a behaviour termed ‘social distancing’. We estimate the effective disease reproduction number and from it infer the maximum degree of social distancing that occurred during the course of the multiple-wave epidemic in Sydney, Australia. We estimate that, on average across the city, people reduced their infectious contact rate by as much as 38%, and that this was sufficient to explain the multiple waves of this epidemic. The basic reproduction number, R(0), was estimated to be in the range of 1.6–2.0 with a preferred estimate of 1.8, in line with other recent estimates for the 1918–1919 influenza pandemic. The data are also consistent with a high proportion (more than 90%) of the population being initially susceptible to clinical infection, and the proportion of infections that were asymptomatic (if this occurs) being no higher than approximately 9%. The observed clinical attack rate of 36.6% was substantially lower than the 59% expected based on the estimated value of R(0), implying that approximately 22% of the population were spared from clinical infection. This reduction in the clinical attack rate translates to an estimated 260 per 100 000 lives having been saved, and suggests that social distancing interventions could play a major role in mitigating the public health impact of future influenza pandemics.",,"['Caley, Peter', 'Philp, David J', 'McCracken, Kevin']",,,,
,PMC,High Prevalence of the CD14-159CC Genotype in Patients Infected with Severe Acute Respiratory Syndrome-Associated Coronavirus,http://dx.doi.org/10.1128/CVI.00100-07,PMC2168372,,,"To investigate whether genetic factors of innate immunity might influence susceptibility and/or progression in individuals infected with SARS, we evaluated the CD14 gene polymorphism in 198 Hong Kong blood donors and 152 Hong Kong severe acute respiratory syndrome (SARS) patients who were previously genotyped for FcγRIIA polymorphisms. The prevalence of the CD14-159CC polymorphism was significantly higher in the patients with severe SARS than in the those with mild SARS or controls (31% versus 15% [mild SARS] or 20% [controls]; mild SARS: P = 0.029; odds ratio, 2.74; 95% confidence interval, 1.15 to 6.57; controls, P = 0.04; odds ratio, 2.41; 95% confidence interval, 1.05 to 5.54), and both CD14-159CC and FcγRIIA-RR131 are risk genotypes for severe SARS-CoV infection.",,"['Yuan, Fang F.', 'Boehm, Ingrid', 'Chan, Paul K. S.', 'Marks, Katherine', 'Tang, Julian W.', 'Hui, David S. C.', 'Sung, Joseph J. Y.', 'Dyer, Wayne B.', 'Geczy, Andrew F.', 'Sullivan, John S.']",,,,
,PMC,Two-Way Antigenic Cross-Reactivity between Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Group 1 Animal CoVs Is Mediated through an Antigenic Site in the N-Terminal Region of the SARS-CoV Nucleoprotein,http://dx.doi.org/10.1128/JVI.01169-07,PMC2168854,,,"In 2002, severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged in humans, causing a global epidemic. By phylogenetic analysis, SARS-CoV is distinct from known CoVs and most closely related to group 2 CoVs. However, no antigenic cross-reactivity between SARS-CoV and known CoVs was conclusively and consistently demonstrated except for group 1 animal CoVs. We analyzed this cross-reactivity by an enzyme-linked immunosorbent assay (ELISA) and Western blot analysis using specific antisera to animal CoVs and SARS-CoV and SARS patient convalescent-phase or negative sera. Moderate two-way cross-reactivity between SARS-CoV and porcine CoVs (transmissible gastroenteritis CoV [TGEV] and porcine respiratory CoV [PRCV]) was mediated through the N but not the spike protein, whereas weaker cross-reactivity occurred with feline (feline infectious peritonitis virus) and canine CoVs. Using Escherichia coli-expressed recombinant SARS-CoV N protein and fragments, the cross-reactive region was localized between amino acids (aa) 120 to 208. The N-protein fragments comprising aa 360 to 412 and aa 1 to 213 reacted specifically with SARS convalescent-phase sera but not with negative human sera in ELISA; the fragment comprising aa 1 to 213 cross-reacted with antisera to animal CoVs, whereas the fragment comprising aa 360 to 412 did not cross-react and could be a potential candidate for SARS diagnosis. Particularly noteworthy, a single substitution at aa 120 of PRCV N protein diminished the cross-reactivity. We also demonstrated that the cross-reactivity is not universal for all group 1 CoVs, because HCoV-NL63 did not cross-react with SARS-CoV. One-way cross-reactivity of HCoV-NL63 with group 1 CoVs was localized to aa 1 to 39 and at least one other antigenic site in the N-protein C terminus, differing from the cross-reactive region identified in SARS-CoV N protein. The observed cross-reactivity is not a consequence of a higher level of amino acid identity between SARS-CoV and porcine CoV nucleoproteins, because sequence comparisons indicated that SARS-CoV N protein has amino acid identity similar to that of infectious bronchitis virus N protein and shares a higher level of identity with bovine CoV N protein within the cross-reactive region. The TGEV and SARS-CoV N proteins are RNA chaperons with long disordered regions. We speculate that during natural infection, antibodies target similar short antigenic sites within the N proteins of SARS-CoV and porcine group 1 CoVs that are exposed to an immune response. Identification of the cross-reactive and non-cross-reactive N-protein regions allows development of SARS-CoV-specific antibody assays for screening animal and human sera.",,"['Vlasova, Anastasia N.', 'Zhang, Xinsheng', 'Hasoksuz, Mustafa', 'Nagesha, Hadya S.', 'Haynes, Lia M.', 'Fang, Ying', 'Lu, Shan', 'Saif, Linda J.']",,,,
,PMC,Antiviral Antibodies Are Necessary To Prevent Cytotoxic T-Lymphocyte Escape in Mice Infected with a Coronavirus,http://dx.doi.org/10.1128/JVI.01580-07,PMC2168833,,,"Mutation within virus-derived CD8 T-cell epitopes can effectively abrogate cytotoxic T-lymphocyte (CTL) recognition and impede virus clearance in infected hosts. These so-called “CTL escape variant viruses” are commonly selected during persistent infections and are associated with rapid disease progression and increased disease severity. Herein, we tested whether antiviral antibody-mediated suppression of virus replication and subsequent virus clearance were necessary for preventing CTL escape in coronavirus-infected mice. We found that compared to wild-type mice, B-cell-deficient mice did not efficiently clear infectious virus, uniformly developed clinical disease, and harbored CTL escape variant viruses. These data directly demonstrate a critical role for antiviral antibody in protecting from the selective outgrowth of CTL escape variant viruses.",,"['Butler, Noah S.', 'Dandekar, Ajai A.', 'Perlman, Stanley']",,,,
,PMC,Bridges to sustainable tropical health,http://dx.doi.org/10.1073/pnas.0700900104,PMC2042158,,,"Ensuring sustainable health in the tropics will require bridge building between communities that currently have a limited track record of interaction. It will also require new organizational innovation if much of the negative health consequences of large-scale economic development projects are to be equitably mitigated, if not prevented. We focus attention on three specific contexts: (i) forging linkages between the engineering and health communities to implement clean water and sanitation on a broad scale to prevent reworming, after the current deworming-only programs, of people by diverse intestinal parasites; (ii) building integrated human and animal disease surveillance infrastructure and technical capacity in tropical countries on the reporting and scientific evidence requirements of the sanitary and phytosanitary agreement under the World Trade Organization; and (iii) developing an independent and equitable organizational structure for health impact assessments as well as monitoring and mitigation of health consequences of economic development projects. Effective global disease surveillance and timely early warning of new outbreaks will require a far closer integration of veterinary and human medicine than heretofore. Many of the necessary surveillance components exist within separate animal- and human-oriented organizations. The challenge is to build the necessary bridges between them.",,"['Singer, Burton H.', 'de Castro, Marcia Caldas']",,,,
,PMC,Human and Avian Influenza Viruses Target Different Cells in the Lower Respiratory Tract of Humans and Other Mammals,http://dx.doi.org/10.2353/ajpath.2007.070248,PMC1988871,,,"Viral attachment to the host cell is critical for tissue and species specificity of virus infections. Recently, pattern of viral attachment (PVA) in human respiratory tract was determined for highly pathogenic avian influenza virus of subtype H5N1. However, PVA of human influenza viruses and other avian influenza viruses in either humans or experimental animals is unknown. Therefore, we compared PVA of two human influenza viruses (H1N1 and H3N2) and two low pathogenic avian influenza viruses (H5N9 and H6N1) with that of H5N1 virus in respiratory tract tissues of humans, mice, ferrets, cynomolgus macaques, cats, and pigs by virus histochemistry. We found that human influenza viruses attached more strongly to human trachea and bronchi than H5N1 virus and attached to different cell types than H5N1 virus. These differences correspond to primary diagnoses of tracheobronchitis for human influenza viruses and diffuse alveolar damage for H5N1 virus. The PVA of low pathogenic avian influenza viruses in human respiratory tract resembled that of H5N1 virus, demonstrating that other properties determine its pathogenicity for humans. The PVA in human respiratory tract most closely mirrored that in ferrets and pigs for human influenza viruses and that in ferrets, pigs, and cats for avian influenza viruses.",,"['van Riel, Debby', 'Munster, Vincent J.', 'de Wit, Emmie', 'Rimmelzwaan, Guus F.', 'Fouchier, Ron A.M.', 'Osterhaus, Albert D.M.E.', 'Kuiken, Thijs']",,,,
,PMC,Opening data to the world: why health numbers matter,http://dx.doi.org/10.2471/BLT.07.046649,PMC2636488,,,,,"Wood, Sara",,,,
,PMC,Common cold,,PMC2231439,,,,,"Worrall, Graham",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus as an Agent of Emerging and Reemerging Infection,http://dx.doi.org/10.1128/CMR.00023-07,PMC2176051,,,"Before the emergence of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) in 2003, only 12 other animal or human coronaviruses were known. The discovery of this virus was soon followed by the discovery of the civet and bat SARS-CoV and the human coronaviruses NL63 and HKU1. Surveillance of coronaviruses in many animal species has increased the number on the list of coronaviruses to at least 36. The explosive nature of the first SARS epidemic, the high mortality, its transient reemergence a year later, and economic disruptions led to a rush on research of the epidemiological, clinical, pathological, immunological, virological, and other basic scientific aspects of the virus and the disease. This research resulted in over 4,000 publications, only some of the most representative works of which could be reviewed in this article. The marked increase in the understanding of the virus and the disease within such a short time has allowed the development of diagnostic tests, animal models, antivirals, vaccines, and epidemiological and infection control measures, which could prove to be useful in randomized control trials if SARS should return. The findings that horseshoe bats are the natural reservoir for SARS-CoV-like virus and that civets are the amplification host highlight the importance of wildlife and biosecurity in farms and wet markets, which can serve as the source and amplification centers for emerging infections.",,"['Cheng, Vincent C. C.', 'Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Yuen, Kwok Yung']",,,,
,PMC,How Relevant is Bellagio Statement of Principles on Social Justice and Influenza to Africa?,,PMC2205980,,,,,"Muula, Adamson S.",,,,
,PMC,In Silico Modeling in Infectious Disease,http://dx.doi.org/10.1016/j.ddmod.2007.09.001,PMC2731239,,,,,"['Daun, Silvia', 'Clermont, Gilles']",,,,
,PMC,Risky trade. Infectious disease in the era of global trade,http://dx.doi.org/10.1136/jech.2007.059659,PMC2652973,,,,,"Torner, Núria",,,,
,PMC,Persistent memory CD4(+) and CD8(+) T-cell responses in recovered severe acute respiratory syndrome (SARS) patients to SARS coronavirus M antigen,http://dx.doi.org/10.1099/vir.0.82839-0,PMC2362397,,,"The membrane (M) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is a major glycoprotein with multiple biological functions. In this study, we found that memory T cells against M protein were persistent in recovered SARS patients by detecting gamma interferon (IFN-γ) production using ELISA and ELISpot assays. Flow cytometric analysis showed that both CD4(+) and CD8(+) T cells were involved in cellular responses to SARS-CoV M antigen. Furthermore, memory CD8(+) T cells displayed an effector memory cell phenotype expressing CD45RO(−) CCR7(−) CD62L(−). In contrast, the majority of IFN-γ(+) CD4(+) T cells were central memory cells with the expression of CD45RO(+) CCR7(+) CD62L(−). The epitope screening from 30 synthetic overlapping peptides that cover the entire SARS-CoV M protein identified four human T-cell immunodominant peptides, p21−44, p65−91, p117−140 and p200−220. All four immunodominant peptides could elicit cellular immunity with a predominance of CD8(+) T-cell response. This data may have important implication for developing SARS vaccines.",,"['Yang, Litao', 'Peng, Hui', 'Zhu, Zhaoling', 'Li, Gang', 'Huang, Zitong', 'Zhao, Zhixin', 'Koup, Richard A.', 'Bailer, Robert T.', 'Wu, Changyou']",,,,
,PMC,Maternal serum concentrations of the chemokine CXCL10/IP-10 are elevated in acute pyelonephritis during pregnancy,http://dx.doi.org/10.1080/14767050701511650,PMC2413055,,,"OBJECTIVE: Acute pyelonephritis is one of the most frequent medical complications of pregnancy, as well as a common cause of antepartum hospitalization. Interferon (IFN)-γ inducible protein, CXCL10/IP-10, is a member of the CXC chemokine family with pro-inflammatory and anti-angiogenic properties. The purpose of this study was to determine whether maternal serum concentrations of CXCL10/IP-10 change in patients with acute pyelonephritis during pregnancy. STUDY DESIGN: This cross-sectional study was conducted to determine the difference in maternal serum concentrations of CXCL10/IP-10 in pregnant women with acute pyelonephritis (N=41) and normal pregnant women (N=89). Pyelonephritis was defined in the presence of a positive urine culture, fever and maternal clinical signs; blood cultures were performed in 36 cases. Maternal serum concentrations of CXCL10/IP-10 were measured by a sensitive immunoassay. Non-parametric statistics were used for analysis. RESULTS: (1) The median serum concentration of CXCL10/IP-10 in pregnant patients with pyelonephritis was significantly higher than in normal pregnant women (median 318.5 pg/mL, range: 78.8–2459.2 vs. median: 116.1 pg/mL, range:40.7–1314.3, respectively; p < 0.001); (2) maternal median serum concentrations of CXCL10/IP-10 did not differ significantly among patients with acute pyelonephritis with and without bacteremia (positive blood cultures: median: 362.6 pg/mL, range: 100.2–2459.2 vs. negative blood cultures: median 298.9 pg/mL, range: 108.5–1148.7, respectively; p = 0.3). CONCLUSIONS: Pyelonephritis in pregnant women is associated with increased maternal serum concentration of the chemokine CXCL10/IP-10.",,"['Gotsch, Francesca', 'Romero, Roberto', 'Espinoza, Jimmy', 'Kusanovic, Juan Pedro', 'Mazaki-Tovi, Shali', 'Erez, Offer', 'Than, Nandor Gabor', 'Edwin, Samuel', 'Mazor, Moshe', 'Yoon, Bo Hyun', 'Hassan, Sonia S.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.01719-07,PMC2045502,,,,,,,,,
,PMC,Pandemic Response and International Health Regulations,http://dx.doi.org/10.1016/S0377-1237(07)80018-9,PMC4922046,,,,,"Agrawal, VK",,,,
,PMC,Identification of a Common Subnuclear Localization Signal,http://dx.doi.org/10.1091/mbc.E07-03-0295,PMC1995723,,,"Proteins share peptidic sequences, such as a nuclear localization signal (NLS), which guide them to particular membrane-bound compartments. Similarities have also been observed within different classes of signals that target proteins to membrane-less subnuclear compartments. Common localization signals affect spatial and temporal subcellular organization and are thought to allow the coordinated response of different molecular networks to a given signaling cue. Here we identify a higher-order and predictive code, {[RR(I/L)X(3)r]((n, n≥1))+[L(φ/N)(V/L)]((n,n>1))}, that establishes high-affinity interactions between a group of proteins and the nucleolus in response to a specific signal. This position-independent code is referred to as a nucleolar detention signal regulated by H(+) (NoDS(H+)) and the class of proteins includes the cIAP2 apoptotic regulator, VHL ubiquitylation factor, HSC70 heat shock protein and RNF8 transcription regulator. By identifying a common subnuclear targeting consensus sequence, our work reveals rules governing the dynamics of subnuclear organization and ascribes new modes of regulation to several proteins with diverse steady-state distributions and dynamic properties.",,"['Mekhail, Karim', 'Rivero-Lopez, Luis', 'Al-Masri, Ahmad', 'Brandon, Caroline', 'Khacho, Mireille', 'Lee, Stephen']",,,,
,PMC,CHRONOBIOLOGY OF HIGH BLOOD PRESSURE,,PMC2613367,,,"BIOCOS, the project aimed at studying BIOlogical systems in their COSmos, has obtained a great deal of expertise in the fields of blood pressure (BP) and heart rate (HR) monitoring and of marker rhythmometry for the purposes of screening, diagnosis, treatment, and prognosis. Prolonging the monitoring reduces the uncertainty in the estimation of circadian parameters; the current recommendation of BIOCOS requires monitoring for at least 7 days. The BIOCOS approach consists of a parametric and a non-parametric analysis of the data, in which the results from the individual subject are being compared with gender- and age-specified reference values in health. Chronobiological designs can offer important new information regarding the optimization of treatment by timing its administration as a function of circadian and other rhythms. New technological developments are needed to close the loop between the monitoring of blood pressure and the administration of antihypertensive drugs.",,"['Cornélissen, G.', 'Halberg, F.', 'Bakken, E. E.', 'Wang, Z.', 'Tarquini, R.', 'Perfetto, F.', 'Laffi, G.', 'Maggioni, C.', 'Kumagai, Y.', 'Homolka, P.', 'Havelková, A.', 'Dušek, J.', 'Svačinová, H.', 'Siegelová, J.', 'Fišer, B.']",,,,
,PMC,Biochemical and Genetic Analyses of Murine Hepatitis Virus Nsp15 Endoribonuclease,http://dx.doi.org/10.1128/JVI.00547-07,PMC2168834,,,"The goal of this project was to better define the relationship between the endoribonuclease activity of murine hepatitis virus (MHV) Nsp15 (mNsp15) and its role in virus infection. Molecular modeling demonstrated that the catalytic residues of mNsp15 are superimposable with its severe acute respiratory syndrome coronavirus ortholog. Alanine substitutions at three key residues in the mNsp15 catalytic pocket (H262, H277, and G275) and a double-mutant version (H262P and H277A) generated proteins with greatly reduced but detectable endoribonuclease activities. Furthermore, these mutant proteins demonstrated lower cleavage specificities for uridylate than wild-type (WT) mNsp15. These mutations were successfully incorporated into viruses named vH262A, vH277A, vG275A, and vH262P+H277A. All four mutant viruses formed plaques with diameters similar to that of MHV-A59 1000 (WT virus) on several different cell lines. Interestingly, viruses with a mutation at a noncatalytic residue, D324A, could not be recovered despite repeated attempts, and expression of mNsp15 containing the D324A mutation in Escherichia coli resulted in an insoluble protein. Plaques derived from vH262A produced approximately 6- to 13-fold fewer PFU than those from WT virus. Cells infected with mNsp15 mutant viruses accumulated lesser amounts of plus- and minus-sense subgenomic RNAs and spike protein than WT virus. The expression of mNsp15 in trans by transient transfection partially restored RNA synthesis by vH262A. These results demonstrate that mNsp15 is required for optimal infection by MHV.",,"['Kang, Hyojeung', 'Bhardwaj, Kanchan', 'Li, Yi', 'Palaninathan, Satheesh', 'Sacchettini, James', 'Guarino, Linda', 'Leibowitz, Julian L.', 'Kao, C. Cheng']",,,,
,PMC,Second look at the spread of epidemics on networks,,PMC2215389,,,"In an important paper, M.E.J. Newman claimed that a general network-based stochastic Susceptible-Infectious-Removed (SIR) epidemic model is isomorphic to a bond percolation model, where the bonds are the edges of the contact network and the bond occupation probability is equal to the marginal probability of transmission from an infected node to a susceptible neighbor. In this paper, we show that this isomorphism is incorrect and define a semi-directed random network we call the epidemic percolation network that is exactly isomorphic to the SIR epidemic model in any finite population. In the limit of a large population, (i) the distribution of (self-limited) outbreak sizes is identical to the size distribution of (small) out-components, (ii) the epidemic threshold corresponds to the phase transition where a giant strongly-connected component appears, (iii) the probability of a large epidemic is equal to the probability that an initial infection occurs in the giant in-component, and (iv) the relative final size of an epidemic is equal to the proportion of the network contained in the giant out-component. For the SIR model considered by Newman, we show that the epidemic percolation network predicts the same mean outbreak size below the epidemic threshold, the same epidemic threshold, and the same final size of an epidemic as the bond percolation model. However, the bond percolation model fails to predict the correct outbreak size distribution and probability of an epidemic when there is a nondegenerate infectious period distribution. We confirm our findings by comparing predictions from percolation networks and bond percolation models to the results of simulations. In an appendix, we show that an isomorphism to an epidemic percolation network can be defined for any time-homogeneous stochastic SIR model.",,"['Kenah, Eben', 'Robins, James M.']",,,,
,PMC,BK Virus Replication In Vitro: Limited Effect of Drugs Interfering with Viral Uptake and Intracellular Transport,http://dx.doi.org/10.1128/AAC.00843-07,PMC2168003,,,"BK virus is an important pathogen in kidney transplant recipients. In vitro studies demonstrated slight antiviral activity for chloroquine and nystatin. A sialic acid derivative, BTB11968, was identified as a lead compound for further development.",,"['Randhawa, Parmjeet', 'Farasati, Noush Afarin', 'Huang, Yuchen']",,,,
,PMC,Adaptive immune cells temper initial innate responses,http://dx.doi.org/10.1038/nm1633,PMC2435248,,,"Toll-like receptors (TLRs) recognize conserved microbial structures called pathogen-associated molecular patterns. Signaling from TLRs leads to upregulation of co-stimulatory molecules for better priming of T cells and secretion of inflammatory cytokines by innate immune cells1–4. Lymphocytedeficient hosts often die of acute infection, presumably owing to their lack of an adaptive immune response to effectively clear pathogens. However, we show here that an unleashed innate immune response due to the absence of residential T cells can also be a direct cause of death. Viral infection or administration of poly(I:C), a ligand for TLR3, led to cytokine storm in T-cell- or lymphocyte-deficient mice in a fashion dependent on NK cells and tumor necrosis factor. We have further shown, through the depletion of CD4(+) and CD8(+) cells in wild-type mice and the transfer of T lymphocytes into Rag-1–deficient mice, respectively, that T cells are both necessary and sufficient to temper the early innate response. In addition to the effects of natural regulatory T cells, close contact of resting CD4(+)CD25(−)Foxp3(−) or CD8(+) T cells with innate cells could also suppress the cytokine surge by various innate cells in an antigen-independent fashion. Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses.",,"['Kim, Kwang Dong', 'Zhao, Jie', 'Auh, Sogyong', 'Yang, Xuanming', 'Du, Peishuang', 'Tang, Hong', 'Fu, Yang-Xin']",,,,
,PMC,Seroepidemiology of group I human coronaviruses in children,http://dx.doi.org/10.1016/j.jcv.2007.08.007,PMC2100388,,,"BACKGROUND: Recently, several new human coronaviruses have been identified. OBJECTIVES: To define the seroepidemiology of group I human coronaviruses STUDY DESIGN: A recombinant protein enzyme linked immunosorbent assay (ELISA) based on portions of the nucleocapsid protein of group I human coronaviruses was developed and was used to screen serum from 243 children and young adults. RESULTS: For HCoV-229E, the percentages of seropositive individuals were 57.1% for infants < 2 months old; 38.9% for infants 2–3 months old; 4.7% for infants 4–5 months old; 42.9–50.0% for infants 6–12 months old; and 34.8–62.5% for individuals 1–20 years old. For HCoV-NL63, the percentages of seropositive individuals were 45.2% for infants < 2 months old; 11.1% for infants 2–3 months old; 4.7% for infants 4–5 months old; 28.6–40.0% for infants 6–12 months old; and 25.0–70.3% for individuals 1–20 years old. CONCLUSIONS: Infection with these viruses is common in childhood though the prevalence of these viruses may vary from year to year.",,"['Shao, Xiuping', 'Guo, Xiaojie', 'Esper, Frank', 'Weibel, Carla', 'Kahn, Jeffrey S.']",,,,
,PMC,Use of Antibody Avidity Assays for Diagnosis of Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/CVI.00056-07,PMC2168165,,,"An indirect immunofluorescent assay (Euroimmun AG, Luebeck, Germany) was used to investigate the avidity of immunoglobulin G (IgG), IgM, IgA, and total Ig (IgGAM) antibody responses to severe acute respiratory syndrome coronavirus (SARS CoV) infections. Serial serum samples from eight patients collected during the first, third, and ninth months after the onset of infection were evaluated. It was found that low-avidity IgG antibodies were detected in 15/15 (100%), 1/5 (20%), and 0/8 (0%) serum samples collected during the first, third, and ninth months after the onset of symptoms, respectively. Low-avidity antibodies of IgA and IgM subclasses were detected in 14/14 (100%) and 3/14 (21%) serum samples, respectively, collected in the first month after the onset of infection. However, IgA antibodies remained low in avidity in a proportion of patients even during late convalescence. As a consequence, IgG antibody avidity assays gave better discrimination between acute-phase and late-convalescent-phase serum samples than IgM, IgA, or IgGAM assays. In two of these patients, sequential serum samples were also tested for IgG avidity against human CoV strains OC43 and 229E in parallel. While SARS CoV infections induced an anamnestic IgG antibody response to the 229E and OC43 viruses, these cross-reactive antibodies remained of high avidity from early (the first month) postinfection. The results showed that assays to detect low-avidity antibody may be useful for discriminating early from late antibody responses and also for distinguishing anamnestic cross-reactive antibody responses from primary specific responses. This may be useful in some clinical situations.",,"['Chan, K. H.', 'Sonnenberg, K.', 'Niedrig, M.', 'Lam, S. Y.', 'Pang, C. M.', 'Chan, K. M.', 'Ma, S. K.', 'Seto, W. H.', 'Peiris, J. S. M.']",,,,
,PMC,Preliminary Evaluation of a Multiplex Reverse Transcription-PCR Assay Combined with a New DNA Chip Hybridization Assay for Detecting Respiratory Syncytial Virus,http://dx.doi.org/10.1128/JCM.00345-07,PMC2168492,,,"DNA chips represent a major advance in microbiology laboratories, enabling the detection of a wide range of possible pathogens using a single test. This study compared a multiplex reverse transcription-PCR combined with DNA chip hybridization (ProDect BCS RV chip; bcs Biotech) with the indirect immunofluorescence test commonly used to detect respiratory viruses. A total of 39 respiratory viruses (38 respiratory syncytial viruses [RSVs] and 1 influenza A virus) were detected in samples from 96 patients using the immunofluorescence test, while 36 viruses (34 RSV, 1 influenza A virus, and 1 influenza B virus) were detected by the DNA chip technique. Results showed a good level of agreement between the two tests for RSV detection; the incidence of other viruses was low, since samples were taken from patients with suspected bronchiolitis. DNA chips displayed high sensitivity (94.6%) and specificity (100%).",,"['Causse, Manuel', 'García-Mayorgas, Ángel D.', 'Gutiérrez, Juan B.', 'Casal, Manuel']",,,,
,PMC,"Noise, nonlinearity and seasonality: the epidemics of whooping cough revisited",http://dx.doi.org/10.1098/rsif.2007.1168,PMC2607388,,,"Understanding the mechanisms that generate oscillations in the incidence of childhood infectious diseases has preoccupied epidemiologists and population ecologists for nearly two centuries. This body of work has generated simple yet powerful explanations for the epidemics of measles and chickenpox, while the dynamics of other infectious diseases, such as whooping cough, have proved more challenging to decipher. A number of authors have, in recent years, proposed that the noisy and somewhat irregular epidemics of whooping cough may arise due to stochasticity and its interaction with nonlinearity in transmission and seasonal variation in contact rates. The reason underlying the susceptibility of whooping cough dynamics to noise and the precise nature of its transient dynamics remain poorly understood. Here we use household data on the incubation period in order to parametrize more realistic distributions of the latent and infectious periods. We demonstrate that previously reported phenomena result from transients following the interaction between the stable annual attractor and unstable multiennial solutions.",,"['Nguyen, Hanh T.H.', 'Rohani, Pejman']",,,,
,PMC,Yeast surface display for protein engineering and characterization,http://dx.doi.org/10.1016/j.sbi.2007.08.012,PMC4038029,,,"Yeast surface display is being employed to engineer desirable properties into proteins for a broad variety of applications. Labeling with soluble ligands enables rapid and quantitative analysis of yeast-displayed libraries by flow cytometry, while libraries with insoluble or even as-yet-uncharacterized binding targets can be screened through cell-surface selections. In parallel, the utilization of yeast surface display for protein characterization, including in particular the mapping of functional epitopes mediating protein-protein interactions, represents a significant recent advance.",,"['Gai, S Annie', 'Wittrup, K Dane']",,,,
,PMC,Profile of Ding-Shinn Chen,http://dx.doi.org/10.1073/pnas.0704698104,PMC2000525,,,,,"Downey, Philip",,,,
,PMC,Network-based analysis of stochastic SIR epidemic models with random and proportionate mixing,http://dx.doi.org/10.1016/j.jtbi.2007.09.011,PMC2186204,,,"In this paper, we outline the theory of epidemic percolation networks and their use in the analysis of stochastic SIR epidemic models on undirected contact networks. We then show how the same theory can be used to analyze stochastic SIR models with random and proportionate mixing. The epidemic percolation networks for these models are purely directed because undirected edges disappear in the limit of a large population. In a series of simulations, we show that epidemic percolation networks accurately predict the mean outbreak size and probability and final size of an epidemic for a variety of epidemic models in homogeneous and heterogeneous populations. Finally, we show that epidemic percolation networks can be used to re-derive classical results from several different areas of infectious disease epidemiology. In an appendix, we show that an epidemic percolation network can be defined for any time-homogeneous stochastic SIR model in a closed population and prove that the distribution of outbreak sizes given the infection of any given node in the SIR model is identical to the distribution of its out-component sizes in the corresponding probability space of epidemic percolation networks. We conclude that the theory of percolation on semi-directed networks provides a very general framework for the analysis of stochastic SIR models in closed populations.",,"['Kenah, Eben', 'Robins, James M.']",,,,
,PMC,Genetically delivered antibody protects against West Nile virus,http://dx.doi.org/10.1016/j.antiviral.2007.08.010,PMC2267767,,,"Gene-based delivery of recombinant antibody genes is a promising therapeutic strategy offering numerous advantages including sustained antibody levels, better safety profile and lower production cost. Here we describe generation of a recombinant antibody Fc-9E2 comprising a fusion protein between human Fc of IgG1 and a single-chain Fv derived from a hybridoma 9E2 secreting a mAb neutralizing West Nile virus (WNV). Fc-9E2 was shown to retain parental mAb's specificity and WNV-neutralizing capacity. Adenovirus-mediated in vivo delivery of the antibody gene resulted in sustained Fc-9E2 serum levels leading to abrogation of lethal WNV infection in an animal model.",,"['Pereboev, Alexander', 'Borisevich, Viktoriya', 'Tsuladze, George', 'Shakhmatov, Mikhail', 'Hudman, Deborah', 'Kazachinskaia, Elena', 'Razumov, Ivan', 'Svyatchenko, Viktor', 'Loktev, Valery', 'Yamshchikov, Vladimir']",,,,
,PMC,Modelling control measures to reduce the impact of pandemic influenza among schoolchildren,http://dx.doi.org/10.1017/S0950268807009284,PMC2870896,,,"We coupled the Wells–Riley equation and the susceptible–exposed–infected–recovery (SEIR) model to quantify the impact of the combination of indoor air-based control measures of enhanced ventilation and respiratory masking in containing pandemic influenza within an elementary school. We integrated indoor environmental factors of a real elementary school and aetiological characteristics of influenza to estimate the age-specific risk of infection (P) and basic reproduction number (R(0)). We combined the enhanced ventilation rates of 0·5, 1, 1·5, and 2/h and respiratory masking with 60%, 70%, 80%, and 95% efficacies, respectively, to predict the reducing level of R(0). We also took into account the critical vaccination coverage rate among schoolchildren. Age-specific P and R(0) were estimated respectively to be 0·29 and 16·90; 0·56 and 16·11; 0·59 and 12·88; 0·64 and 16·09; and 0·07 and 2·80 for five age groups 4–6, 7–8, 9–10, 11–12, and 25–45 years, indicating pre-schoolchildren have the highest transmission potential. We conclude that our integrated approach, employing the mechanism of transmission of indoor respiratory infection, population-dynamic transmission model, and the impact of infectious control programmes, is a powerful tool for risk profiling prediction of pandemic influenza among schoolchildren.",,"['CHEN, S.-C.', 'LIAO, C.-M.']",,,,
,PMC,Highly Pathogenic Avian Influenza H5N1 Viruses Elicit an Attenuated Type I Interferon Response in Polarized Human Bronchial Epithelial Cells,http://dx.doi.org/10.1128/JVI.01134-07,PMC2169033,,,"The unparalleled spread of highly pathogenic avian influenza A (HPAI) H5N1 viruses has resulted in devastating outbreaks in domestic poultry and sporadic human infections with a high fatality rate. To better understand the mechanism(s) of H5N1 virus pathogenesis and host responses in humans, we utilized a polarized human bronchial epithelial cell model that expresses both avian alpha-2,3- and human alpha-2,6-linked sialic acid receptors on the apical surface and supports productive replication of both H5N1 and H3N2 viruses. Using this model, we compared the abilities of selected 2004 HPAI H5N1 viruses isolated from humans and a recent human H3N2 virus to trigger the type I interferon (IFN) response. H5N1 viruses elicited significantly less IFN regulatory factor 3 (IRF3) nuclear translocation, as well as delayed and reduced production of IFN-β compared with the H3N2 virus. Furthermore, phosphorylation of Stat2 and induction of IFN-stimulated genes (ISGs), such as MX1, ISG15, IRF7, and retinoic acid-inducible gene I, were substantially delayed and reduced in cells infected with H5N1 viruses. We also observed that the highly virulent H5N1 virus replicated more efficiently and induced a weaker IFN response than the H5N1 virus that exhibited low virulence in mammals in an earlier study. Our data suggest that the H5N1 viruses tested, especially the virus with the high-pathogenicity phenotype, possess greater capability to attenuate the type I IFN response than the human H3N2 virus. The attenuation of this critical host innate immune defense may contribute to the virulence of H5N1 viruses observed in humans.",,"['Zeng, Hui', 'Goldsmith, Cynthia', 'Thawatsupha, Pranee', 'Chittaganpitch, Malinee', 'Waicharoen, Sunthareeya', 'Zaki, Sherif', 'Tumpey, Terrence M.', 'Katz, Jacqueline M.']",,,,
,PMC,Genetic Analysis of Murine Hepatitis Virus nsp4 in Virus Replication,http://dx.doi.org/10.1128/JVI.01257-07,PMC2169011,,,"Coronavirus replicase polyproteins are translated from the genomic positive-strand RNA and are proteolytically processed by three viral proteases to yield 16 mature nonstructural proteins (nsp1 to nsp16). nsp4 contains four predicted transmembrane-spanning regions (TM1, -2, -3, and -4), demonstrates characteristics of an integral membrane protein, and is thought to be essential for the formation and function of viral replication complexes on cellular membranes. To determine the requirement of nsp4 for murine hepatitis virus (MHV) infection in culture, engineered deletions and mutations in TMs and intervening soluble regions were analyzed for effects on virus recovery, growth, RNA synthesis, protein expression, and intracellular membrane modifications. In-frame partial or complete deletions of nsp4; deletions of TM1, -2, and -3; and alanine substitutions of multiple conserved, clustered, charged residues in nsp4 resulted in viruses that were nonrecoverable, viruses highly impaired in growth and RNA synthesis, and viruses that were nearly wild type in replication. The results indicate that nsp4 is required for MHV replication and that while putative TM1, -2, and -3 and specific charged residues may be essential for productive virus infection, putative TM4 and the carboxy-terminal amino acids K(398) through T(492) of nsp4 are dispensable. Together, the experiments identify important residues and regions for studies of nsp4 topology, function, and interactions.",,"['Sparks, Jennifer S.', 'Lu, Xiaotao', 'Denison, Mark R.']",,,,
,PMC,Isolation of Avian Paramyxovirus 1 from a Patient with a Lethal Case of Pneumonia,http://dx.doi.org/10.1128/JVI.01406-07,PMC2168997,,,"An unknown virus was isolated from a lung biopsy sample and multiple other samples from a patient who developed a lethal case of pneumonia following a peripheral blood stem cell transplant. A random PCR-based molecular screening method was used to identify the infectious agent as avian paramyxovirus 1 (APMV-1; a group encompassing Newcastle disease virus), which is a highly contagious poultry pathogen that has only rarely been found in human infections. Immunohistochemical analysis confirmed the presence of APMV-1 antigen in sloughed alveolar cells in lung tissue from autopsy. Sequence from the human isolate showed that it was most closely related to virulent pigeon strains of APMV-1. This is the most completely documented case of a systemic human infection caused by APMV-1 and is the first report of an association between this virus and a fatal disease in a human.",,"['Goebel, Scott J.', 'Taylor, Jill', 'Barr, Bradd C.', 'Kiehn, Timothy E.', 'Castro-Malaspina, Hugo R.', 'Hedvat, Cyrus V.', 'Rush-Wilson, Kim A.', 'Kelly, Cassandra D.', 'Davis, Stephen W.', 'Samsonoff, William A.', 'Hurst, Kelley R.', 'Behr, Melissa J.', 'Masters, Paul S.']",,,,
,PMC,Localization and Membrane Topology of Coronavirus Nonstructural Protein 4: Involvement of the Early Secretory Pathway in Replication,http://dx.doi.org/10.1128/JVI.01506-07,PMC2168994,,,"The coronavirus nonstructural proteins (nsp's) derived from the replicase polyproteins collectively constitute the viral replication complexes, which are anchored to double-membrane vesicles. Little is known about the biogenesis of these complexes, the membrane anchoring of which is probably mediated by nsp3, nsp4, and nsp6, as they contain several putative transmembrane domains. As a first step to getting more insight into the formation of the coronavirus replication complex, the membrane topology, processing, and subcellular localization of nsp4 of the mouse hepatitis virus (MHV) and severe acute respiratory syndrome-associated coronavirus (SARS-CoV) were elucidated in this study. Both nsp4 proteins became N glycosylated, while their amino and carboxy termini were localized to the cytoplasm. These observations imply nsp4 to assemble in the membrane as a tetraspanning transmembrane protein with a Nendo/Cendo topology. The amino terminus of SARS-CoV nsp4, but not that of MHV nsp4, was shown to be (partially) processed by signal peptidase. nsp4 localized to the endoplasmic reticulum (ER) when expressed alone but was recruited to the replication complexes in infected cells. nsp4 present in these complexes did not colocalize with markers of the ER or Golgi apparatus, while the susceptibility of its sugars to endoglycosidase H indicated that the protein had also not traveled trough the latter compartment. The important role of the early secretory pathway in formation of the replication complexes was also demonstrated by the inhibition of coronaviral replication when the ER export machinery was blocked by use of the kinase inhibitor H89 or by expression of a mutant, Sar1[H79G].",,"['Oostra, M.', 'te Lintelo, E. G.', 'Deijs, M.', 'Verheije, M. H.', 'Rottier, P. J. M.', 'de Haan, C. A. M.']",,,,
,PMC,Influenza Virus mRNA Translation Revisited: Is the eIF4E Cap-Binding Factor Required for Viral mRNA Translation?,http://dx.doi.org/10.1128/JVI.01105-07,PMC2168979,,,"Influenza virus mRNAs bear a short capped oligonucleotide sequence at their 5′ ends derived from the host cell pre-mRNAs by a “cap-snatching” mechanism, followed immediately by a common viral sequence. At their 3′ ends, they contain a poly(A) tail. Although cellular and viral mRNAs are structurally similar, influenza virus promotes the selective translation of its mRNAs despite the inhibition of host cell protein synthesis. The viral polymerase performs the cap snatching and binds selectively to the 5′ common viral sequence. As viral mRNAs are recognized by their own cap-binding complex, we tested whether viral mRNA translation occurs without the contribution of the eIF4E protein, the cellular factor required for cap-dependent translation. Here, we show that influenza virus infection proceeds normally in different situations of functional impairment of the eIF4E factor. In addition, influenza virus polymerase binds to translation preinitiation complexes, and furthermore, under conditions of decreased eIF4GI association to cap structures, an increase in eIF4GI binding to these structures was found upon influenza virus infection. This is the first report providing evidence that influenza virus mRNA translation proceeds independently of a fully active translation initiation factor (eIF4E). The data reported are in agreement with a role of viral polymerase as a substitute for the eIF4E factor for viral mRNA translation.",,"['Burgui, Idoia', 'Yángüez, Emilio', 'Sonenberg, Nahum', 'Nieto, Amelia']",,,,
,PMC,Rapid Multiplex Nested PCR for Detection of Respiratory Viruses,http://dx.doi.org/10.1128/JCM.00280-07,PMC2168518,,,"Respiratory tract infections can be caused by a heterogeneous group of viruses and bacteria that produce similar clinical presentations. Specific diagnosis therefore relies on laboratory investigation. This study developed and evaluated five groups of multiplex nested PCR assays that could simultaneously detect 21 different respiratory pathogens: influenza A virus (H1N1, H3N2, and H5N1); influenza B virus; parainfluenza virus types 1, 2, 3, 4a, and 4b; respiratory syncytial virus A and B; human rhinoviruses; human enteroviruses; human coronaviruses OC43 and 229E; severe acute respiratory syndrome coronavirus; human metapneumoviruses; Mycoplasma pneumoniae; Chlamydophila pneumoniae; Legionella pneumophila; and adenoviruses (A to F). These multiplex nested PCRs adopted fast PCR technology. The high speed of fast PCR (within 35 min) greatly improved the efficiency of these assays. The results show that these multiplex nested PCR assays are specific and more sensitive (100- to 1,000-fold) than conventional methods. Among the 303 clinical specimens tested, the multiplex nested PCR achieved an overall positive rate of 48.5% (95% confidence interval [CI], 42.9 to 54.1%), which was significantly higher than that of virus isolation (20.1% [95% CI, 15.6 to 24.6%]) and that of direct detection by immunofluorescence assay (13.5% [95% CI, 9.7 to 17.4%]). The improved sensitivity was partly due to the higher sensitivity of multiplex nested PCR than that of conventional methods in detecting cultivatable viruses. Moreover, the ability of the multiplex nested PCR to detect noncultivatable viruses, particularly rhinoviruses, coronavirus OC43, and metapneumoviruses, contributed a major gain (15.6%) in the overall positive rate. In conclusion, rapid multiplex nested PCR assays can improve the diagnostic yield for respiratory infections to allow prompt interventive actions to be taken.",,"['Lam, W. Y.', 'Yeung, Apple C. M.', 'Tang, Julian W.', 'Ip, Margaret', 'Chan, Edward W. C.', 'Hui, Mamie', 'Chan, Paul K. S.']",,,,
,PMC,"Clinical Features and Complete Genome Characterization of a Distinct Human Rhinovirus (HRV) Genetic Cluster, Probably Representing a Previously Undetected HRV Species, HRV-C, Associated with Acute Respiratory Illness in Children",http://dx.doi.org/10.1128/JCM.01254-07,PMC2168475,,,"Although human rhinoviruses (HRVs) are common causes of respiratory illness, their molecular epidemiology has been poorly investigated. Despite the recent findings of new HRV genotypes, their clinical disease spectrum and phylogenetic positions were not fully understood. In this study, 203 prospectively collected nasopharyngeal aspirates (NPAs), negative for common respiratory viruses (83 were human bocavirus [HBoV] positive and 120 HBoV negative), from hospitalized children during a 1-year period were subjected to reverse transcription-PCR for HRV. HRV was detected in 14 NPAs positive and 12 NPAs negative for HBoV. Upon VP4 gene analysis, 5 of these 26 HRV strains were found to belong to HRV-A while 21 belonged to a genetic clade probably representing a previously undetected HRV species, HRV-C, that is phylogenetically distinct from the two known HRV species, HRV-A and HRV-B. The VP4 sequences of these HRV-C strains were closely related to the newly identified HRV strains from the United States and Australia. Febrile wheeze or asthma was the most common presentation (76%) of HRV-C infection, which peaked in fall and winter. Complete genome sequencing of three HRV-C strains revealed that HRV-C represents an additional HRV species, with features distinct from HRV-A and HRV-B. Analysis of VP1 of HRV-C revealed major deletions in regions important for neutralization in other HRVs, which may be signs of a distinct species, while within-clade amino acid variation in potentially antigenic regions may indicate the existence of different serotypes among HRV-C strains. A newly identified HRV species, HRV-C, is circulating worldwide and is an important cause of febrile wheeze and asthmatic exacerbations in children requiring hospitalization.",,"['Lau, Susanna K. P.', 'Yip, Cyril C. Y.', 'Tsoi, Hoi-wah', 'Lee, Rodney A.', 'So, Lok-yee', 'Lau, Yu-lung', 'Chan, Kwok-hung', 'Woo, Patrick C. Y.', 'Yuen, Kwok-yung']",,,,
,PMC,High Fidelity of Murine Hepatitis Virus Replication Is Decreased in nsp14 Exoribonuclease Mutants,http://dx.doi.org/10.1128/JVI.01296-07,PMC2169014,,,"Replication fidelity of RNA virus genomes is constrained by the opposing necessities of generating sufficient diversity for adaptation and maintaining genetic stability, but it is unclear how the largest viral RNA genomes have evolved and are maintained under these constraints. A coronavirus (CoV) nonstructural protein, nsp14, contains conserved active-site motifs of cellular exonucleases, including DNA proofreading enzymes, and the severe acute respiratory syndrome CoV (SARS-CoV) nsp14 has 3′-to-5′ exoribonuclease (ExoN) activity in vitro. Here, we show that nsp14 ExoN remarkably increases replication fidelity of the CoV murine hepatitis virus (MHV). Replacement of conserved MHV ExoN active-site residues with alanines resulted in viable mutant viruses with growth and RNA synthesis defects that during passage accumulated 15-fold more mutations than wild-type virus without changes in growth fitness. The estimated mutation rate for ExoN mutants was similar to that reported for other RNA viruses, whereas that of wild-type MHV was less than the established rates for RNA viruses in general, suggesting that CoVs with intact ExoN replicate with unusually high fidelity. Our results indicate that nsp14 ExoN plays a critical role in prevention or repair of nucleotide incorporation errors during genome replication. The established mutants are unique tools to test the hypothesis that high replication fidelity is required for the evolution and stability of large RNA genomes.",,"['Eckerle, Lance D.', 'Lu, Xiaotao', 'Sperry, Steven M.', 'Choi, Leena', 'Denison, Mark R.']",,,,
,PMC,Rat coronaviruses infect rat alveolar type I epithelial cells and induce expression of CXC chemokines,http://dx.doi.org/10.1016/j.virol.2007.07.030,PMC2170429,,,"We analyzed the ability of two rat coronavirus (RCoV) strains, sialodacryoadenitis virus (SDAV) and Parker’s RCoV (RCoV-P), to infect rat alveolar type I cells and induce chemokine expression. Primary rat alveolar type II cells were transdifferentiated into the type I cell phenotype. Type I cells were productively infected with SDAV and RCoV-P, and both live virus and UV-inactivated virus induced mRNA and protein expression of three CXC chemokines: CINC-2, CINC-3, and LIX, which are neutrophil chemoattractants. Dual immunolabeling of type I cells for viral antigen and CXC chemokines showed that chemokines were expressed primarily by uninfected cells. Virus-induced chemokine expression was reduced by the IL-1 receptor antagonist, suggesting that IL-1 produced by infected cells induces uninfected cells to express chemokines. Primary cultures of alveolar epithelial cells are an important model for the early events in viral infection that lead to pulmonary inflammation.",,"['Miura, Tanya A.', 'Wang, Jieru', 'Holmes, Kathryn V.', 'Mason, Robert J.']",,,,
,PMC,The Chickens Come Home to Roost,http://dx.doi.org/10.2105/AJPH.2006.090431,PMC1963309,,,,,"Benatar, David",,,,
,PMC,State Health Policy for Terrorism Preparedness,http://dx.doi.org/10.2105/AJPH.2006.101436,PMC1963278,,,"State health policy for terrorism preparedness began before the terrorist attacks on September 11, 2001, but was accelerated after that day. In a crisis atmosphere after September 11, the states found their policies changing rapidly, greatly influenced by federal policies and federal dollars. In the 5 years since September 11, these state health policies have been refined. This refinement has included a restatement of the goals and objectives of state programs, the modernization of emergency powers statutes, the education and training of the public health workforce, and a preparation of the health care system to better care for victims of disasters, including acts of terrorism.",,"['Ziskin, Leah Z.', 'Harris, Drew A.']",,,,
,PMC,"Infectious diseases are spreading more rapidly than ever before, WHO warns",http://dx.doi.org/10.1136/bmj.39318.516968.DB,PMC1962876,,,,,"O'Dowd, Adrian",,,,
,PMC,Bloodletting and miraculous cures,,PMC2234638,,,,,"Lock, Michael",,,,
,PMC,Are We Ready? Evidence of Support Mechanisms for Canadian Health Care Workers in Multi-jurisdictional Emergency Planning,http://dx.doi.org/10.1007/BF03405419,PMC6975624,,,"BACKGROUND: Federal, provincial and municipal leaders in Canada have adopted a culture of preparedness with the development and update of emergency plans in anticipation of different types of disasters. As evident during the 2003 global outbreak of Severe Acute Respiratory Syndrome (SARS), it is important to provide support for health care workers (HCWs) who are vulnerable during infectious outbreak scenarios. Here we focus on the identification and evaluation of existing support mechanisms incorporated within emergency plans across various jurisdictional levels. METHODS: Qualitative content analysis of 12 emergency plans from national, provincial and municipal levels were conducted using NVIVOTM software. The plans were scanned and coded according to 1) informational, 2) instrumental, and 3) emotional support mechanisms for HCWs and other first responders. RESULTS: Emergency plans were comprised of a predominance of informational and instrumental supports, yet few emotional or social support mechanisms. All the plans lacked gender-based analysis of how infectious disease outbreaks impact male and female HCWs differently. Acknowledgement of the need for emotional supports was evident at higher jurisdictional levels, but recommended for implementation locally. CONCLUSIONS: While support mechanisms for HCWs are included in this sample of emergency plans, content analysis revealed few emotional or social supports planned for critical personnel; particularly for those who will be required to work in extremely stressful conditions under significant personal risk. The implications of transferring responsibilities for support to local and institutional jurisdictions are discussed.",,"['O’sullivan, Tracey L.', 'Amaratunga, Carol A.', 'Hardt, Jill', 'Dow, Darcie', 'Phillips, Karen P.', 'Corneil, Wayne']",,,,
,PMC,"Effects of ambient temperature on volume, specialty composition and triage levels of emergency department visits",http://dx.doi.org/10.1136/emj.2006.045310,PMC2464652,,,"AIM: To evaluate the effects of change of ambient temperature on emergency department (ED) patient visits. METHODS: This prospective observational study was conducted in the ED of National Taiwan University Hospital from January 2002 to January 2007. The daily ED patient numbers of different triage levels in different service specialties were collected and correlated with the daily average temperature (T) and change in temperature (ΔT) compared with the previous day. A univariate analysis was performed with the Pearson correlation and a multivariate analysis with multiple linear regression analysis. RESULTS: A total of 505 224 patient visits were included in this study. On univariate analysis, there was no significant correlation between T and the ED volume (r = 0.012, p = 0.608), but there was a significant correlation between ΔT and ED volume (r = 0.109, p<0.001). On multivariate analysis, ΔT and holidays were identified as independent predictors of ED volume. We established the following formula in predicting the ED patient number: y = 265.42+(0.06×T)+(2.57×ΔT)+(59.77×holiday). There was a positive association between T and the trauma patient number, while there was a negative association between T and medical and paediatric patient numbers. On the triage level, a low T was associated with increased patient triage level, while no significant association was noted between ΔT and the proportion in any triage level. CONCLUSIONS: Our study demonstrated that ambient temperature had differential effects on ED patient visits of different specialties and severities.",,"['Tai, Chia‐Chun', 'Lee, Chien‐Chang', 'Shih, Chung‐Liang', 'Chen, Shyr‐Chyr']",,,,
,PMC,Pandemic Influenza Planning in Nursing Homes: Are We Prepared?,http://dx.doi.org/10.1111/j.1532-5415.2007.01299.x,PMC3319394,,,"Avian influenza or Influenza A (H5N1) is caused by a viral strain that occurs naturally in wild birds, but to which humans are immunologically naïve. If an influenza pandemic occurs, it is expected to have dire consequences, including millions of deaths, social disruption, and enormous economic consequences. The Department of Health and Human Resources plan, released in November 2005, clearly affirms the threat of a pandemic. Anticipating a disruption in many factions of society, every segment of the healthcare industry, including nursing homes, will be affected and will need to be self-sufficient. Disruption of vaccine distribution during the seasonal influenza vaccine shortage during the 2004/05 influenza season is but one example of erratic emergency planning. Nursing homes will have to make vital decisions and provide care to older adults who will not be on the initial priority list for vaccine. At the same time, nursing homes will face an anticipated shortage of antiviral medications and be expected to provide surge capacity for overwhelmed hospitals. This article provides an overview of current recommendations for pandemic preparedness and the potential effect of a pandemic on the nursing home industry. It highlights the need for collaborative planning and dialogue between nursing homes and various stakeholders already heavily invested in pandemic preparedness.",,"['Mody, Lona', 'Cinti, Sandro']",,,,
,PMC,Bringing chronic disease epidemiology and infectious disease epidemiology back together,http://dx.doi.org/10.1136/jech.2006.057752,PMC2660008,,,,,"['Choi, Bernard C K', 'Morrison, Howard', 'Wong, Tom', 'Wu, Jun', 'Yan, Yong‐Ping']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.01609-07,PMC2045392,,,,,,,,,
,PMC,Conductance and amantadine binding of a pore formed by a lysine-flanked transmembrane domain of SARS coronavirus envelope protein,http://dx.doi.org/10.1110/ps.062730007,PMC2206980,,,"The coronavirus responsible for the severe acute respiratory syndrome (SARS-CoV) contains a small envelope protein, E, with putative involvement in host cell apoptosis and virus morphogenesis. It has been suggested that E protein can form a membrane destabilizing transmembrane (TM) hairpin, or homooligomerize to form a regular TM α-helical bundle. We have shown previously that the topology of the α-helical putative TM domain of E protein (ETM), flanked by two lysine residues at C and N termini to improve solubility, is consistent with a regular TM α-helix, with orientational parameters in lipid bilayers that are consistent with a homopentameric model. Herein, we show that this peptide, reconstituted in lipid bilayers, shows sodium conductance. Channel activity is inhibited by the anti-influenza drug amantadine, which was found to bind our preparation with moderate affinity. Results obtained from single or double mutants indicate that the organization of the transmembrane pore is consistent with our previously reported pentameric α-helical bundle model.",,"['Torres, Jaume', 'Maheswari, Uma', 'Parthasarathy, Krupakar', 'Ng, Lifang', 'Liu, Ding Xiang', 'Gong, Xiandi']",,,,
,PMC,"Can the Health-Care System Meet the Challenge of Pandemic Flu? Planning, Ethical, and Workforce Considerations",,PMC1936949,,,"The federal pandemic influenza plan predicts that 30% of the population could be infected. The impact of this pandemic would quickly overwhelm the public health and health-care delivery systems in the U.S. and throughout the world. Surge capacity for staffing, availability of drugs and supplies, and alternate means to provide care must be included in detailed plans that are tested and drilled ahead of time. Accurate information on the disease must be made available to health-care staff and the public to reduce fear. Spokespersons must provide clear, consistent messages about the disease, including actions to be taken to contain its spread and treat the afflicted. Home care will be especially important, as hospitals will be quickly overwhelmed. Staff must be prepared ahead of time to assure their ability and willingness to report to work, and public health must plan ahead to adequately confront ethical issues that will arise concerning the availability of treatment resources. The entire community must work together to meet the challenges posed by an epidemic. Identification and resolution of these challenges and issues are essential to achieve adequate public health preparedness.",,"['Levin, Peter J.', 'Gebbie, Eric N.', 'Qureshi, Kristine']",,,,
,PMC,REGULATION OF IRF-3 DEPENDENT INNATE IMMUNITY BY THE PAPAIN-LIKE                     PROTEASE DOMAIN OF THE SARS CORONAVIRUS,http://dx.doi.org/10.1074/jbc.M704870200,PMC2756044,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) is a novel coronavirus that causes a highly contagious respiratory disease, SARS, with significant mortality. While factors contributing to the highly pathogenic nature of SARS-CoV remain poorly understood, it has been reported that SARS-CoV infection does not induce type I interferons (IFNs) in cell culture. However, it is uncertain whether SARS-CoV evades host detection or has evolved mechanisms to counteract innate host defenses. We show here that infection of SARS-CoV triggers a weak IFN response in cultured human lung/bronchial epithelial cells without inducing the phosphorylation of IFN-regulatory factor 3 (IRF-3), a latent cellular transcription factor that is pivotal for type I IFN synthesis. Furthermore, SARS-CoV infection blocked the induction of IFN antiviral activity and the upregulation of protein expression of a subset of IFN-stimulated genes triggered by dsRNA or an unrelated paramyxovirus. In searching for a SARS-CoV protein capable of counteracting innate immunity, we identified the papain-like protease (PLpro) domain as a potent IFN antagonist. The inhibition of the IFN response does not require the protease activity of PLpro. Rather, PLpro interacts with IRF-3, and inhibits the phosphorylation and nuclear translocation of IRF-3, thereby disrupting the activation of type I IFN responses through either Toll-like receptor 3 or retinoic acid inducible gene I/melanoma differentiation-associated gene 5 pathways. Our data suggest that regulation of IRF-3-dependent innate antiviral defenses by PLpro may contribute to the establishment of SARS-CoV infection.",,"['Devaraj, Santhana G.', 'Wang, Nan', 'Chen, Zhongbin', 'Chen, Zihong', 'Tseng, Monica', 'Barretto, Naina', 'Lin, Rongtuan', 'Peters, Clarence J.', 'Tseng, Chien-Te K.', 'Baker, Susan C.', 'Li, Kui']",,,,
,PMC,"Structural, Biochemical, and in Vivo Characterization of the First Virally Encoded Cyclophilin from the Mimivirus",http://dx.doi.org/10.1016/j.jmb.2007.08.051,PMC2884007,,,"Although multiple viruses utilize host cell cyclophilins, including severe acute respiratory syndrome (SARS) and human immunodeficiency virus type-1(HIV-1), their role in infection is poorly understood. To help elucidate these roles, we have characterized the first virally encoded cyclophilin (mimicyp) derived from the largest virus discovered to date (the Mimivirus) that is also a causative agent of pneumonia in humans. Mimicyp adopts a typical cyclophilin-fold, yet it also forms trimers unlike any previously characterized homologue. Strikingly, immunofluorescence assays reveal that mimicyp localizes to the surface of the mature virion, as recently proposed for several viruses that recruit host cell cyclophilins such as SARS and HIV-1. Additionally mimicyp lacks peptidyl-prolyl isomerase activity in contrast to human cyclophilins. Thus, this study suggests that cyclophilins, whether recruited from host cells (i.e. HIV-1 and SARS) or virally encoded (i.e. Mimivirus), are localized on viral surfaces for at least a subset of viruses.",,"['Thai, Vu', 'Renesto, Patricia', 'Fowler, C. Andrew', 'Brown, Darin J.', 'Davis, Tara', 'Gu, Wanjun', 'Pollock, David D.', 'Kern, Dorothee', 'Raoult, Didier', 'Eisenmesser, Elan Z.']",,,,
,PMC,Nuclear Magnetic Resonance Structure of the N-Terminal Domain of Nonstructural Protein 3 from the Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.00969-07,PMC2168779,,,"This paper describes the structure determination of nsp3a, the N-terminal domain of the severe acute respiratory syndrome coronavirus (SARS-CoV) nonstructural protein 3. nsp3a exhibits a ubiquitin-like globular fold of residues 1 to 112 and a flexibly extended glutamic acid-rich domain of residues 113 to 183. In addition to the four β-strands and two α-helices that are common to ubiquitin-like folds, the globular domain of nsp3a contains two short helices representing a feature that has not previously been observed in these proteins. Nuclear magnetic resonance chemical shift perturbations showed that these unique structural elements are involved in interactions with single-stranded RNA. Structural similarities with proteins involved in various cell-signaling pathways indicate possible roles of nsp3a in viral infection and persistence.",,"['Serrano, Pedro', 'Johnson, Margaret A.', 'Almeida, Marcius S.', 'Horst, Reto', 'Herrmann, Torsten', 'Joseph, Jeremiah S.', 'Neuman, Benjamin W.', 'Subramanian, Vanitha', 'Saikatendu, Kumar S.', 'Buchmeier, Michael J.', 'Stevens, Raymond C.', 'Kuhn, Peter', 'Wüthrich, Kurt']",,,,
,PMC,Programmed Ribosomal Frameshifting in SIV is Induced by a Highly Structured RNA Stem-Loop,http://dx.doi.org/10.1016/j.jmb.2007.08.033,PMC2080864,,,"Simian Immunodeficiency Virus (SIV), like its human homologues (HIV-1, HIV-2), requires a −1 translational frameshift event to properly synthesize all of the proteins required for viral replication. The frameshift mechanism is dependent upon a seven nucleotide slippery sequence and a downstream RNA structure. In SIV, the downstream RNA structure has been proposed to be either a stem-loop or a pseudoknot. Here, we report the functional, structural and thermodynamic characterization of the SIV frameshift site RNA. Translational frameshift assays indicate that a stem-loop structure is sufficient to promote efficient frameshifting in vitro. NMR and thermodynamic studies of SIV RNA constructs of varying length further support the absence of any pseudoknot interaction and indicate the presence of a stable stem-loop structure. We determined the structure of the SIV frameshift-inducing RNA by NMR. The structure reveals a highly ordered 12 nucleotide loop containing a sheared G-A pair, cross-strand adenine stacking, two G-C base-pairs, and a novel CCC triloop turn. The loop structure and its high thermostability preclude pseudoknot formation. Sequence conservation and modeling studies suggest that HIV-2 RNA forms the same structure. We conclude that, like the main sub-groups of HIV-1, SIV and HIV-2 utilize stable stem-loop structures to function as a thermodynamic barrier to translation, thereby inducing ribosomal pausing and frameshifting.",,"['Marcheschi, Ryan J.', 'Staple, David W.', 'Butcher, Samuel E.']",,,,
,PMC,Specific Asparagine-Linked Glycosylation Sites Are Critical for DC-SIGN- and L-SIGN-Mediated Severe Acute Respiratory Syndrome Coronavirus Entry,http://dx.doi.org/10.1128/JVI.00315-07,PMC2168787,,,"Severe acute respiratory syndrome (SARS) is caused by a newly emerged coronavirus (CoV) designated SARS-CoV. The virus utilizes angiotensin-converting enzyme 2 (ACE2) as the primary receptor. Although the idea is less clear and somewhat controversial, SARS-CoV is thought to use C-type lectins DC-SIGN and/or L-SIGN (collectively referred to as DC/L-SIGN) as alternative receptors or as enhancer factors that facilitate ACE2-mediated virus infection. In this study, the function of DC/L-SIGN in SARS-CoV infection was examined in detail. The results of our study clearly demonstrate that both proteins serve as receptors independently of ACE2 and that there is a minimal level of synergy between DC/L-SIGN and ACE2. As expected, glycans on spike (S) glycoprotein are important for DC/L-SIGN-mediated virus infection. Site-directed mutagenesis analyses have identified seven glycosylation sites on the S protein critical for DC/L-SIGN-mediated virus entry. They include asparagine residues at amino acid positions 109, 118, 119, 158, 227, 589, and 699, which are distinct from residues of the ACE2-binding domain (amino acids 318 to 510). Amino acid sequence analyses of S proteins encoded by viruses isolated from animals and humans suggest that glycosylation sites N227 and N699 have facilitated zoonotic transmission.",,"['Han, Dong P.', 'Lohani, Motashim', 'Cho, Michael W.']",,,,
,PMC,Vaccines Based on Novel Adeno-Associated Virus Vectors Elicit Aberrant CD8(+) T-Cell Responses in Mice,http://dx.doi.org/10.1128/JVI.01253-07,PMC2168776,,,"We recently discovered an expanded family of adeno-associated viruses (AAVs) that show promise as improved gene therapy vectors. In this study we evaluated the potential of vectors based on several of these novel AAVs as vaccine carriers for human immunodeficiency virus type 1 Gag. Studies with mice indicated that vectors based on AAV type 7 (AAV7), AAV8, and AAV9 demonstrate improved immunogenicity in terms of Gag CD8(+) T-cell and Gag antibody responses. The quality of these antigen-specific responses was evaluated in detail for AAV2/8 vectors and compared to results with an adenovirus vector expressing Gag (AdC7). AAV2/8 produced a vibrant CD8(+) T-cell effector response characterized by coexpression of gamma interferon and tumor necrosis factor alpha as well as in vivo cytolytic activity. No CD8(+) T-cell response generated by any of the AAVs was effectively boosted with AdC7, a result consistent with the finding of a relative lack of cells expressing interleukin-2 (IL-2) or a central memory phenotype at 3 months after the prime. The primary response to an AdC7 vaccine differed from that generated by AAVs in that the peak effector response evolved into populations of Gag-specific T cells expressing high levels of cytokines, including IL-2, and with effector memory and central memory phenotypes. A number of mechanisms could be considered to explain the aberrant activation of CD8(+) T cells by AAV, including insufficient inflammatory responses, CD4 help, and/or chronic antigen expression and T-cell exhaustion. Interestingly, the B-cell response to AAV-encoded Gag was quite vibrant and easily boosted with AdC7.",,"['Lin, Jianping', 'Zhi, Yan', 'Mays, Lauren', 'Wilson, James M.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Evades Antiviral Signaling: Role of nsp1 and Rational Design of an Attenuated Strain,http://dx.doi.org/10.1128/JVI.00702-07,PMC2168762,,,"The severe acute respiratory syndrome (SARS) epidemic was caused by the spread of a previously unrecognized infectious agent, the SARS-associated coronavirus (SARS-CoV). Here we show that SARS-CoV could inhibit both virus- and interferon (IFN)-dependent signaling, two key steps of the antiviral response. We mapped a strong inhibitory activity to SARS-CoV nonstructural protein 1 (nsp1) and show that expression of nsp1 significantly inhibited the activation of all three virus-dependent signaling pathways. We show that expression of nsp1 significantly inhibited IFN-dependent signaling by decreasing the phosphorylation levels of STAT1 while having little effect on those of STAT2, JAK1, and TYK2. We engineered an attenuated mutant of nsp1 in SARS-CoV through reverse genetics, and the resulting mutant virus was viable and replicated as efficiently as wild-type virus in cells with a defective IFN response. However, mutant virus replication was strongly attenuated in cells with an intact IFN response. Thus, nsp1 is likely a virulence factor that contributes to pathogenicity by favoring SARS-CoV replication.",,"['Wathelet, Marc G.', 'Orr, Melissa', 'Frieman, Matthew B.', 'Baric, Ralph S.']",,,,
,PMC,Lung Delivery Studies Using siRNA Conjugated to TAT(48-60) and Penetratin Reveal Peptide Induced Reduction in Gene Expression and Induction of Innate Immunity,http://dx.doi.org/10.1021/bc070077d,PMC2621305,,,"The therapeutic application of siRNA shows promise as an alternative approach to small molecule inhibitors for the treatment of human disease. However, the major obstacle to its use has been the difficulty in delivering these large anionic molecules in vivo. In this study, we have investigated whether siRNA-mediated knockdown of p38 MAP kinase mRNA in mouse lung is influenced by conjugation to the non-viral delivery vector cholesterol and the cell penetrating peptides (CPP) TAT(48-60) and penetratin. Initial studies in the mouse fibroblast L929 cell line, showed that siRNA conjugated to cholesterol, TAT(48-60) and penetratin but not siRNA alone achieved a limited reduction of p38 MAP kinase mRNA expression. Intratracheal administration of siRNA resulted in localisation within macrophages and scattered epithelial cells and produced a 30-45% knockdown of p38 MAP kinase mRNA at 6hrs. As with increasing doses of siRNA, conjugation to cholesterol improved upon the duration but not the magnitude of mRNA knockdown whilst penetratin and TAT(48-60) had no effect. Importantly, administration of the penetratin or TAT(48-60) peptides alone caused significant reduction in p38 MAP kinase mRNA expression whilst the penetratin-siRNA conjugate activated the innate immune response. Overall, these studies suggest that conjugation to cholesterol may extend but not increase siRNA mediated p38 MAP kinase mRNA knockdown in the lung. Furthermore, the use of CPP may be limited due to as yet uncharacterized effects upon gene expression and a potential for immune activation.",,"['Moschos, Sterghios Athanasios', 'Jones, Simon Wyn', 'Perry, Mark Michael', 'Williams, Andrew Evan', 'Erjefalt, Jonas Sten', 'Turner, John James', 'Barnes, Peter John', 'Sproat, Brian Stephen', 'Gait, Michael John', 'Lindsay, Mark Andrew']",,,,
,PMC,Novel Small-Molecule Inhibitors of Transmissible Gastroenteritis Virus,http://dx.doi.org/10.1128/AAC.00408-07,PMC2151441,,,"We used swine testicle (ST) cells infected with transmissible gastroenteritis virus (TGEV) and an indirect immunofluorescent assay with antibodies against TGEV spike and nucleocapsid proteins to screen small-molecule compounds that inhibit TGEV replication. Analogues of initial hits were collected and subjected to a 3CL protease (3CL(pro)) inhibition assay with recombinant 3CL(pro) and a fluorogenic peptide substrate. A series of benzothiazolium compounds were found to have inhibitory activity against TGEV 3CL(pro) and to exert anti-TGEV activities in terms of viral protein and RNA replication in TGEV-infected ST cells, with consequent protection of TGEV-infected ST cells from cytopathic effect by blocking the activation of caspase-3.",,"['Yang, Cheng-Wei', 'Yang, Yung-Ning', 'Liang, Po-Huang', 'Chen, Chi-Min', 'Chen, Wei-Liang', 'Chang, Hwan-You', 'Chao, Yu-Sheng', 'Lee, Shiow-Ju']",,,,
,PMC,The Atg5–Atg12 conjugate associates with innate antiviral immune responses,http://dx.doi.org/10.1073/pnas.0704014104,PMC1955809,,,"Autophagy is an essential process for physiological homeostasis, but its role in viral infection is only beginning to be elucidated. We show here that the Atg5–Atg12 conjugate, a key regulator of the autophagic process, plays an important role in innate antiviral immune responses. Atg5-deficient mouse embryonic fibroblasts (MEFs) were resistant to vesicular stomatitis virus replication, which was largely due to hyperproduction of type I interferons in response to immunostimulatory RNA (isRNA), such as virus-derived, double-stranded, or 5′-phosphorylated RNA. Similar hyperresponse to isRNA was also observed in Atg7-deficient MEFs, in which Atg5–Atg12 conjugation is impaired. Overexpression of Atg5 or Atg12 resulted in Atg5–Atg12 conjugate formation and suppression of isRNA-mediated signaling. Molecular interaction studies indicated that the Atg5–Atg12 conjugate negatively regulates the type I IFN production pathway by direct association with the retinoic acid-inducible gene I (RIG-I) and IFN-β promoter stimulator 1 (IPS-1) through the caspase recruitment domains (CARDs). Thus, in contrast to its role in promoting the bactericidal process, a component of the autophagic machinery appears to block innate antiviral immune responses, thereby contributing to RNA virus replication in host cells.",,"['Jounai, Nao', 'Takeshita, Fumihiko', 'Kobiyama, Kouji', 'Sawano, Asako', 'Miyawaki, Atsushi', 'Xin, Ke-Qin', 'Ishii, Ken J.', 'Kawai, Taro', 'Akira, Shizuo', 'Suzuki, Koichi', 'Okuda, Kenji']",,,,
,PMC,"Structure-based Design, Synthesis and Biological Evaluation of Peptidomimetic SARS-CoV 3CLpro Inhibitors",http://dx.doi.org/10.1016/j.bmcl.2007.08.031,PMC2112940,,,"Structure-based design, synthesis and biological evaluation of a series of peptidomimetic severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors is described. These inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 1 bound to SARS-CoV 3CLpro. Incorporation of Boc-Ser as the P4-ligand resulted in enhanced SARS-CoV 3CLpro inhibitory activity. Structural analysis of inhibitor-bound X-ray structure revealed high binding affinity towards the enzyme.",,"['Ghosh, Arun K.', 'Xi, Kai', 'Grum-Tokars, Valerie', 'Xu, Xiaoming', 'Ratia, Kiira', 'Fu, Wentao', 'Houser, Katherine V.', 'Baker, Susan C.', 'Johnson, Michael E.', 'Mesecar, Andrew D.']",,,,
,PMC,The clinical and public health value of non-culture methods in the investigation of a cluster of unexplained pneumonia cases,http://dx.doi.org/10.1017/S0950268807009302,PMC2870888,,,"During 2003, a cluster of initially unexplained pneumonia cases (two fatal) occurred in patients aged <50 years in a British city. Routine culture tests were inconclusive, however, pneumococcal infection was suspected and the putative outbreak was investigated using non-culture methods. Clinical samples from ten patients were tested by pneumococcal polymerase chain reaction (PCR) and multi-locus sequence typing (MLST), or Binax NOW(®) pneumococcal urine antigen test and serotype-specific enzyme-linked immunosorbent assay (ELISA). Lung samples from the deceased patients were PCR positive and yielded different MLST types. Two patients in one family group were serotype 1 pneumococcal antigen positive. Two further patients were serotype 1 antigen positive, and one serotype 4 positive. Two antigen-positive cases were also serum PCR positive. Non-culture methods confirmed the disease aetiology in six cases. Serotype and MLST results showed no single outbreak, but a family cluster of cases in a high background of pneumococcal pneumonia, providing important epidemiological data that would not otherwise have been available.",,"['SHEPPARD, C.\xa0L.', 'SALMON, J.\xa0E.', 'HARRISON, T.\xa0G.', 'LYONS, M.', 'GEORGE, R.\xa0C.']",,,,
,PMC,Discovery and Development of Antiviral Drugs for Biodefense: Experience of a Small Biotechnology Company,http://dx.doi.org/10.1016/j.antiviral.2007.07.003,PMC2972676,,,"The unmet need for effective antivirals against potential agents of bioterrorism and emerging infections is obvious; however, the challenges to developing such drugs are daunting. Even with the passage of Project BioShield and more recently the BARDA legislation, there is still not a clear market for these types of drugs and limited federal funding available to support expensive drug development studies. SIGA Technologies, Inc. is a small biotech company committed to developing novel products for the prevention and treatment of severe infectious diseases, with an emphasis on products for diseases that could result from bioterrorism. Through trials and error SIGA has developed an approach to this problem in order to establish the infrastructure necessary to successfully advance new antiviral drugs from the discovery stage on through to licensure. The approach that we have taken to drug development is biology driven and dependent on a dispersive development model utilizing essential collaborations with academic, federal, and private sector partners. This consortium approach requires success in acquiring grants and contracts as well as iterative communication with the government and regulatory agencies. However, it can work as evidenced by the rapid progress of our lead antiviral against smallpox, ST-246, and should serve as the template for development of new antivirals against important biological pathogens.",,"['Bolken, Tove C.', 'Hruby, Dennis E.']",,,,
,PMC,"Seroepidemiology of Human Bocavirus in Hokkaido Prefecture, Japan",http://dx.doi.org/10.1128/JCM.02140-06,PMC2045318,,,"A new human virus, provisionally named human bocavirus (HBoV), was discovered by Swedish researchers in 2005. A new immunofluorescence assay using Trichoplusia ni insect cells infected with a recombinant baculovirus expressing the VP1 protein of HBoV was developed, and the levels of immunoglobulin G antibody to the VP1 protein of HBoV in serum samples were measured. The overall seroprevalence rate of antibodies against the VP1 protein of HBoV in a Japanese population aged from 0 months to 41 years was 71.1% (145 of 204). The seropositive rate was lowest in the age group of 6 to 8 months and gradually increased with age. All of the children had been exposed to HBoV by the age of 6 years. A rise in titers of antibody against the VP1 protein of HBoV during the convalescent phase was observed for four patients with lower respiratory tract infections, and HBoV DNA was detected in nasopharyngeal swab and serum samples from all four patients. These results suggest that HBoV is a ubiquitous virus acquired early in life and that HBoV might play a role in the course of lower respiratory tract infections.",,"['Endo, Rika', 'Ishiguro, Nobuhisa', 'Kikuta, Hideaki', 'Teramoto, Shinobu', 'Shirkoohi, Reza', 'Ma, Xiaoming', 'Ebihara, Takashi', 'Ishiko, Hiroaki', 'Ariga, Tadashi']",,,,
,PMC,Involvement of IL-10 in the suppression of antibody production by in vitro immunized peripheral blood mononuclear cells,http://dx.doi.org/10.1007/s10616-007-9088-x,PMC2104556,,,"Previously, we have established an in vitro immunization method to induce antigen-specific antibody-producing B cells. In the present study, we have attempted to clarify the mechanisms that regulate antibody production by in vitro immunized peripheral blood mononuclear cells (PBMC). Freshly isolated PBMC did not induce antibody production following in vitro immunization, but expressed the interleukin (IL)-10 gene. On the other hand, PBMC pretreated with l-leucyl-l-leucine methyl ester (LLME) induced antibody production, but did not express the IL-10 gene. IL-10 induced functional impairment of CD4(+) Th cells and CD11c(+) DC, resulting in the suppression of antibody production by in vitro immunized PBMC.",,"['Yamashita, Makiko', 'Katakura, Yoshinori', 'Aiba, Yoshihiro', 'Matsumoto, Shin-ei', 'Morihara, Kazuko', 'Teruya, Kiichiro', 'Ichikawa, Akira', 'Shirahata, Sanetaka']",,,,
,PMC,"Arenavirus Entry Occurs Through a Cholesterol-Dependent, Non-Caveolar, Clathrin-Mediated Endocytic Mechanism",http://dx.doi.org/10.1016/j.virol.2007.07.014,PMC2227908,,,"Arenaviruses are important causes of viral hemorrhagic fevers in humans. Arenavirus infection of cells occurs via a pH dependent endocytic route, but detailed studies of entry pathways have not been done. We investigated the role of cell membrane cholesterol, caveolae, and clathrin coated pits in infection by Lassa virus (LASV), which utilizes alpha-dystroglycan (α-DG) as a receptor, and Pichindé virus (PICV), which does not. Depletion of cellular cholesterol by treatment with methyl betacyclodextrin (MβCD) or nystatin/progesterone inhibited PICV replication and transfer of packaged marker gene by LASV or PICV pseudotyped retroviral particles. In cells lacking caveolae due to silencing of the caveolin-1 gene, no inhibition of PICV infection or LASV pseudotype transduction was observed. However, PICV infection and LASV and PICV pseudotype transduction was inhibited when an Eps15 dominant negative mutant was used to inhibit clathrin-mediated endocytosis. Altogether, the results indicate that diverse arenaviruses have a common requirement for cell membrane cholesterol and clathrin mediated endocytosis in establishing infection.",,"['Vela, Eric M.', 'Zhang, Lihong', 'Colpitts, Tonya M.', 'Davey, Robert A.', 'Aronson, Judith F.']",,,,
,PMC,Human CD4(+) Memory T-lymphocyte Responses to SARS Coronavirus Infection,http://dx.doi.org/10.1016/j.virol.2007.07.015,PMC2094716,,,"Little is known about CD4(+) T-cell immunity to the severe acute respiratory syndrome (SARS) coronavirus. In two SARS patients, we examined the memory CD4(+) T-cell responses to peptides derived from SARS coronavirus structural proteins. We generated CD4(+) T-cell lines to 3 peptides from the spike (S) protein and defined their HLA restriction. In one patient, the predominant memory CD4(+) T-cell response was directed against an epitope outside the S protein receptor binding domain. In both patients, the frequency of CD4(+) memory T-cells to virus structural proteins and anti-SARS coronavirus IgG levels were low by 12 months after infection. This report expands our understanding of the specificity and duration of anti-SARS coronavirus CD4(+) T-cell immune responses.",,"['Libraty, Daniel H.', 'O’Neil, Kimberly M.', 'Baker, Lauren M.', 'Acosta, Luz P.', 'Olveda, Remigio M.']",,,,
,PMC,Systemic but not mucosal immunity induced by AVA prevents inhalational anthrax,http://dx.doi.org/10.1016/j.micinf.2007.08.002,PMC2117355,,,"Improved vaccines and adjuvants are being developed to reduce the threat posed by a terrorist attack involving aerosolized anthrax spores. Nevertheless, uncertainty persists concerning the relative benefits of inducing mucosal vs systemic immunity to host survival following inhalational exposure to anthrax spores. This work examines the effect of delivering the licensed human vaccine (Anthrax Vaccine Adsorbed, AVA) combined with a CpG oligodeoxynucleotide (ODN) adjuvant intraperitoneally or intranasally to A/J mice. Results indicate that protection from inhalational anthrax correlates with the induction of a strong systemic rather than mucosal immune response, and demonstrate that protection is significantly improved and accelerated by the addition of CpG ODN.",,"['Klinman, Dennis M.', 'Currie, Debra', 'Lee, Gloria', 'Grippe, Vanessa', 'Merkel, Tod']",,,,
,PMC,Immunization by Avian H5 Influenza Hemagglutinin Mutants with Altered Receptor Binding Specificity,http://dx.doi.org/10.1126/science.1135165,PMC2367145,,,"Influenza virus entry is mediated by the receptor binding domain (RBD) of its spike, the hemagglutinin (HA). Adaptation of avian viruses to humans is associated with HA specificity for α2,6- rather than α2,3-linked sialic acid (SA) receptors. Here, we define mutations in influenza A subtype H5N1 (avian) HA that alter its specificity for SA either by decreasing α2,3- or increasing α2,6-SA recognition. RBD mutants were used to develop vaccines and monoclonal antibodies that neutralized new variants. Structure-based modification of HA specificity can guide the development of preemptive vaccines and therapeutic monoclonal antibodies that can be evaluated before the emergence of human-adapted H5N1 strains.",,"['Yang, Zhi-Yong', 'Wei, Chih-Jen', 'Kong, Wing-Pui', 'Wu, Lan', 'Xu, Ling', 'Smith, David F.', 'Nabel, Gary J.']",,,,
,PMC,Relating Diarrheal Disease to Social Networks and the Geographic Configuration of Communities in Rural Ecuador,http://dx.doi.org/10.1093/aje/kwm184,PMC2391301,,,"Social networks and geographic structures of communities are important predictors of infectious disease transmission. To examine their joint effects on diarrheal disease and how these effects might develop, the authors analyzed social network and geographic data from northern coastal Ecuador and examined associations with diarrhea prevalence. Between July 2003 and May 2005, 113 cases of diarrhea were identified in nine communities. Concurrently, sociometric surveys were conducted, and households were mapped with geographic information systems. Spatial distribution metrics of households within communities and of communities with respect to roads were developed that predict social network degree in casual contact (“contact”) and food-sharing (“food”) networks. The mean degree is 25-40% lower in communities with versus without road access and 66-94% lower in communities with lowest versus highest housing density. Associations with diarrheal disease were found for housing density (comparing dense with dispersed communities: risk ratio = 3.3, 95% confidence interval (CI): 1.1, 10.0) and social connectedness (comparing lowest with highest degree communities: risk ratio = 3.4, 95% CI: 1.1, 10.1 in the contact network and risk ratio = 4.9, 95% CI: 1.1, 21.9 in the food network). Some of these differences may be related to more new residents, lower housing density, and less social connectedness in road communities.",,"['Bates, Sarah J.', 'Trostle, James', 'Cevallos, William T.', 'Hubbard, Alan', 'Eisenberg, Joseph N. S.']",,,,
,PMC,RAP80 interacts with the SUMO-conjugating enzyme UBC9 and is a novel target for sumoylation,http://dx.doi.org/10.1016/j.bbrc.2007.07.158,PMC2049087,,,"RAP80, a nuclear protein with two functional ubiquitin interaction motifs (UIMs) at its N-terminus, plays a critical role in the regulation of estrogen receptor alpha and DNA damage response signaling. A yeast two-hybrid screen identified the SUMO-conjugating enzyme UBC9 as a protein interacting with RAP80. The interaction of RAP80 with UBC9 was confirmed by co-immunoprecipitation and GST pull-down analyses. The region between a.a. 122–204 was critical for the interaction of RAP80 with UBC9. In addition, we demonstrate that RAP80 is a target for SUMO-1 modification in intact cells. Expression of UBC9 enhanced RAP80 mono-sumoylation and also induced multisumoylation of RAP80. In addition to SUMO-1, RAP80 was efficiently conjugated to SUMO-3 but was only a weak substrate for SUMO-2 conjugation. These findings suggest that sumoylation plays a role in the regulation of RAP80 functions.",,"['Yan, Jun', 'Yang, Xiao-Ping', 'Kim, Yong-Sik', 'Joo, Joung Hyuck', 'Jetten, Anton M.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Gene 7 Products Contribute to Virus-Induced Apoptosis,http://dx.doi.org/10.1128/JVI.01266-07,PMC2045523,,,"The proteins encoded by gene 7 of the severe acute respiratory syndrome coronavirus (SARS-CoV) have been demonstrated to have proapoptotic activity when expressed from cDNA but appear to be dispensable for virus replication. Recombinant SARS-CoVs bearing deletions in gene 7 were used to assess the contribution of gene 7 to virus replication and apoptosis in several transformed cell lines, as well as to replication and pathogenesis in golden Syrian hamsters. Deletion of gene 7 had no effect on SARS-CoV replication in transformed cell lines, nor did it alter the induction of early apoptosis markers such as annexin V binding and activation of caspase 3. However, viruses with gene 7 disruptions were not as efficient as wild-type virus in inducing DNA fragmentation, as judged by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, indicating that the gene 7 products do contribute to virus-induced apoptosis. Disruption of gene 7 did not affect virus replication or morbidity in golden Syrian hamsters, suggesting that the gene 7 products are not required for acute infection in vivo. The data indicate that open reading frames 7a and 7b contribute to but are not solely responsible for the apoptosis seen in SARS-CoV-infected cells.",,"['Schaecher, Scott R.', 'Touchette, Erin', 'Schriewer, Jill', 'Buller, R. Mark', 'Pekosz, Andrew']",,,,
,PMC,Partial protection against H5N1 influenza in mice with a single dose of a chimpanzee adenovirus vector expressing nucleoprotein,http://dx.doi.org/10.1016/j.vaccine.2007.07.035,PMC2748222,,,"The development of adenoviral vectors based on non-human serotypes such as the chimpanzee adenovirus AdC7 may allow for their utilization in populations harboring neutralizing antibodies to common human serotypes. Because adenoviral vectors can be used to generate potent T cell responses, they may be useful as vaccines against pandemic influenza such as may be caused by the H5N1 strains that are currently endemic in avian populations. The influenza nucleoprotein (NP) is known to provide MHC Class I restricted epitopes that are effective in evoking a cytolytic response. Because there is only low sequence variation in NP sequences between different influenza strains, a T cell vaccine may provide heterosubtypic protection against a spectrum of influenza A strains. An AdC7 vector expressing the influenza A/Puerto Rico/8/34 NP was tested for its efficacy in protecting BALB/c mice against two H5N1 strains and compared to a conventional human adenovirus serotype 5 vaccine. The AdC7 NP vaccine elicited a strong anti-NP T cell response. When tested in a mouse challenge model, there was improved survival following challenge with two strains of H5N1 that have caused human outbreaks, Vietnam/1203/04 and Hong Kong/483/97, although the improved survival reached statistical significance only with the strain from Vietnam.",,"['Roy, Soumitra', 'Kobinger, Gary P.', 'Lin, Jianping', 'Figueredo, Joanita', 'Calcedo, Roberto', 'Kobasa, Darwyn', 'Wilson, James M.']",,,,
,PMC,A multi-data source surveillance system to detect a bioterrorism attack during the G8 Summit in Scotland,http://dx.doi.org/10.1017/S0950268807009132,PMC2870879,,,"In 18 weeks, Health Protection Scotland (HPS) deployed a syndromic surveillance system to early-detect natural or intentional disease outbreaks during the G8 Summit 2005 at Gleneagles, Scotland. The system integrated clinical and non-clinical datasets. Clinical datasets included Accident & Emergency (A&E) syndromes, and General Practice (GPs) codes grouped into syndromes. Non-clinical data included telephone calls to a nurse helpline, laboratory test orders, and hotel staff absenteeism. A cumulative sum-based detection algorithm and a log-linear regression model identified signals in the data. The system had a fax-based track for real-time identification of unusual presentations. Ninety-five signals were triggered by the detection algorithms and four forms were faxed to HPS. Thirteen signals were investigated. The system successfully complemented a traditional surveillance system in identifying a small cluster of gastroenteritis among the police force and triggered interventions to prevent further cases.",,"['MEYER, N.', 'McMENAMIN, J.', 'ROBERTSON, C.', 'DONAGHY, M.', 'ALLARDICE, G.', 'COOPER, D.']",,,,
,PMC,"Structural basis for the binding of the neutralizing antibody, 7D11, to the poxvirus L1 protein",http://dx.doi.org/10.1016/j.virol.2007.06.042,PMC2100026,,,"Medical countermeasures to prevent or treat smallpox are needed due to the potential use of poxviruses as biological weapons. Safety concerns with the currently available smallpox vaccine indicate a need for research on alternative poxvirus vaccine strategies. Molecular vaccines involving the use of proteins and/or genes and recombinant antibodies are among the strategies under current investigation. The poxvirus L1 protein, encoded by the L1R open reading frame, is the target of neutralizing antibodies and has been successfully used as a component of both protein subunit and DNA vaccines. L1-specific monoclonal antibodies (e.g., mouse monoclonal antibody mAb-7D11, mAb-10F5) with potent neutralizing activity bind L1 in a conformation-specific manner. This suggests that proper folding of the L1 protein used in molecular vaccines will affect the production of neutralizing antibodies and protection. Here, we co-crystallized the Fab fragment of mAb-7D11 with the L1 protein. The crystal structure of the complex between Fab-7D11 and L1 reveals the basis for the conformation-specific binding as recognition of a discontinuous epitope containing two loops that are held together by a disulfide bond. The structure of this important conformational epitope of L1 will contribute to the development of molecular poxvirus vaccines and also provides a novel target for anti-poxvirus drugs. In addition, the sequence and structure of Fab-7D11 will contribute to the development of L1-targeted immunotherapeutics.",,"['Su, Hua-Poo', 'Golden, Joseph W.', 'Gittis, Apostolos G.', 'Hooper, Jay W.', 'Garboczi, David N.']",,,,
,PMC,More medicines for neglected and emerging infectious diseases,http://dx.doi.org/10.2471/BLT.07.045690,PMC2636391,,,,,"Radisch, Jack",,,,
,PMC,Is type 2 diabetes a surgical disease?,,PMC2386163,,,,,"Anvari, Mehran",,,,
,PMC,The emergence of porcine circovirus 2b genotype (PCV-2b) in swine in Canada,,PMC1914312,,,"Since late 2004, the swine industry in the province of Quebec has experienced a significant increase in death rate related to postweaning multisystemic wasting syndrome (PMWS). To explain this phenomenon, 2 hypotheses were formulated: 1) the presence of a 2nd pathogen could be exacerbating the porcine circovirus 2 (PCV-2) infection, or 2) a new and more virulent PCV-2 strain could be infecting swine. In 2005, 13 PMWS cases were submitted to the Quebec provincial diagnostic laboratory and PCV-2 was the only virus that could be found consistently by PCR in all 13 samples. The PCR detection results obtained for other viruses revealed the following: 61.5% were positive for porcine reproductive and respiratory syndrome virus, 30.8% for swine influenza virus, 15.4% for porcine parvovirus, 69.2% for swine torque teno virus (swTTV), 38.5% for swine hepatitis E virus (swHEV) and 84.6% for Mycoplasma hyorhinis; transmissible gastroenteritis virus and porcine respiratory coronavirus (TGEV/PRCV) was not detected. Sequences of the entire genome revealed that these PCV-2 strains belonged to a genotype (named PCV-2b) that has never been reported in Canada. Further sequence analyses on 83 other Canadian PCV-2 positive cases submitted to the provincial diagnostic laboratory during years 2005 and 2006 showed that 79.5% of the viral sequences obtained clustered in the PCV-2b genotype. The appearance of the PCV-2b genotype in Canada may explain the death rate increase related to PMWS, but this relationship has to be confirmed.",,"['Gagnon, Carl A.', 'Tremblay, Donald', 'Tijssen, Peter', 'Venne, Marie-Hélène', 'Houde, Alain', 'Elahi, Seyyed Mehdy']",,,,
,PMC,Role of Law Enforcement Response and Microbial Forensics in                     Investigation of Bioterrorism,,PMC2080552,,,"The risk and threat of bioterrorism and biocrime have become a large concern and challenge for governments and society to enhance biosecurity. Law enforcement plays an important role in assessing and investigating activities involved in an event of bioterrorism or biocrime. Key to a successful biosecurity program is increased awareness and early detection of threats facilitated by an integrated network of responsibilities and capabilities from government, academic, private, and public assets. To support an investigation, microbial forensic sciences are employed to analyze and characterize forensic evidence with the goal of attribution or crime scene reconstruction. Two different molecular biology-based assays – real time polymerase chain reaction (PCR) and repetitive element PCR – are described and demonstrate how molecular biology tools may be utilized to aid in the investigative process. Technologies relied on by microbial forensic scientists need to be properly validated so that the methods used are understood and so that interpretation of results is carried out within the limitations of the assays. The three types of validation are preliminary, developmental, and internal. The first is necessary for rapid response when a threat is imminent or an attack has recently occurred. The latter two apply to implementation of routinely used procedures.",,"['Budowle, Bruce', 'Beaudry, Jodi A.', 'Barnaby, Neel G.', 'Giusti, Alan M.', 'Bannan, Jason D.', 'Keim, Paul']",,,,
,PMC,Integrating Public Health and Primary Care,,PMC2645118,,,"PURPOSE: Improved health and social outcomes would be possible with better coordination and collaboration between public health and primary care. The purpose of this study is to identify linkages between these health sectors with the aim of informing a forward-looking policy approach to integrate public health functions in primary care. METHODS: We searched national and international journals and the grey literature for relevant papers and reports published from January 1999 to December 2003. The final set of documents provided broad coverage of the topic, with emphasis on national and international representation and a special focus on disease surveillance, health promotion, accident and illness prevention and chronic diseases. RESULTS: Three main findings emerged from this study. First, there is a need to understand and clearly articulate the roles and functions of public health and primary care in Canada. Second, the main areas of overlap between these sectors are health surveillance, health promotion and prevention of disease and injury. Third, based on an international literature search, we identified 10 models that demonstrate how these sectors can be integrated; five of them were developed in Canada. CONCLUSIONS: National and international evidence and a variety of working models support the integration of public health functions in primary care. Canada has been a leader in developing models of integrated health systems that combine individualized approaches to influence personal health behaviour and community approaches to influence the health of the population. These integration models could be further developed through a focus on the common need of primary care and public health to address the health implications of the ever-present risk of emerging infectious diseases in Canada.",,"['Stevenson Rowan, Margo', 'Hogg, William', 'Huston, Patricia']",,,,
,PMC,The Cytoplasmic Tails of Uukuniemi Virus (Bunyaviridae) G(N) and G(C) Glycoproteins Are Important for Intracellular Targeting and the Budding of Virus-Like Particles,http://dx.doi.org/10.1128/JVI.00767-07,PMC2045573,,,"Functional motifs within the cytoplasmic tails of the two glycoproteins G(N) and G(C) of Uukuniemi virus (UUK) (Bunyaviridae family) were identified with the help of our recently developed virus-like particle (VLP) system for UUK virus (A. K. Overby, V. Popov, E. P. Neve, and R. F. Pettersson, J. Virol. 80:10428-10435, 2006). We previously reported that information necessary for the packaging of ribonucleoproteins into VLPs is located within the G(N) cytoplasmic tail (A. K. Overby, R. F. Pettersson, and E. P. Neve, J. Virol. 81:3198-3205, 2007). The G(N) glycoprotein cytoplasmic tail specifically interacts with the ribonucleoproteins and is critical for genome packaging. In addition, two other regions in the G(N) cytoplasmic tail, encompassing residues 21 to 25 and 46 to 50, were shown to be important for particle generation and release. By the introduction of point mutations within these two regions, we demonstrate that leucines at positions 23 and 24 are crucial for the initiation of VLP budding, while leucine 46, glutamate 47, and leucine 50 are important for efficient exit from the endoplasmic reticulum and subsequent transport to the Golgi complex. We found that budding and particle generation are highly dependent on the intracellular localization of both glycoproteins. The short cytoplasmic tail of UUK G(C) contains a lysine at position −3 from the C terminus that is highly conserved among members of the Phlebovirus, Hantavirus, and Orthobunyavirus genera. Mutating this single amino acid residue in G(C) resulted in the mislocalization of not only G(C) but also G(N) to the plasma membrane, and VLP generation was compromised in cells expressing this mutant. Together, these results demonstrate that the cytoplasmic tails of both G(N) and G(C) contain specific information necessary for efficient virus particle generation.",,"['Överby, Anna K.', 'Popov, Vsevolod L.', 'Pettersson, Ralf F.', 'Neve, Etienne P. A.']",,,,
,PMC,Assembly of Hepatitis B Virus Envelope Proteins onto a Lentivirus Pseudotype That Infects Primary Human Hepatocytes,http://dx.doi.org/10.1128/JVI.00959-07,PMC2045538,,,"This study demonstrates that the envelope proteins of hepatitis B virus (HBV) could be incorporated into the lipid membrane of lentivirus pseudotype particles. The assembly procedure was initiated by the transfection of 293T cells with three plasmids: (i) a human immunodeficiency virus (HIV) packaging construct, (ii) a transfer plasmid expressing a reporter gene, and (iii) a plasmid expressing large (L), middle (M), and small (S) HBV envelope proteins. After 2 days, hepatitis B surface antigen and the antigenic forms of L, M, and S were detected at the cell surface by flow cytometry. Also, virus particles that were able to infect cultured primary human hepatocytes (PHH) were released. Under optimal conditions, 50% of PHH could be infected. In addition, the susceptibility of PHH and the resistance of other cell types to the pseudotype particles were similar to those observed for HBV and hepatitis delta virus (HDV), which shares the same L, M, and S. Furthermore, the infection of PHH by the pseudotype was sensitive to known inhibitors of HBV and HDV entry. These findings of specific and efficient infection of hepatocytes could be applicable to liver-specific gene therapy and may help clarify the attachment and entry mechanism used by HBV and HDV.",,"['Chai, Ning', 'Chang, Ho Eun', 'Nicolas, Emmanuelle', 'Gudima, Severin', 'Chang, Jinhong', 'Taylor, John']",,,,
,PMC,The Coronavirus Spike Protein Induces Endoplasmic Reticulum Stress and Upregulation of Intracellular Chemokine mRNA Concentrations,http://dx.doi.org/10.1128/JVI.01033-07,PMC2045536,,,"Murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS) coronavirus (CoV) are two of the best-studied representatives of the family Coronaviridae. During CoV infection, numerous cytokines and chemokines are induced in vitro and in vivo. Human interleukin 8 and its mouse functional counterpart, CXCL2, are early-expressed chemokines. Here we show that SARS-CoV and MHV induce endoplasmic reticulum (ER) stress and Cxcl2 mRNA transcription during infection in vitro. Expression of the viral spike protein significantly induced ER stress and Cxcl2 mRNA upregulation, while expression of the other structural genes did not. Additional experiments with UV-inactivated virus, cell-cell fusion-blocking antibodies, and an MHV mutant with a defect in spike protein maturation demonstrated that spike-host interactions in the ER are responsible for the induction of ER stress and subsequent Cxcl2 mRNA transcription. Despite significant increases in levels of Cxcl2 mRNA and functional nucleus-to-cytoplasm RNA transport, no CXCL2 protein was released into the medium from MHV-infected cells. Yet Sendai virus-infected cells showed substantial Cxcl2 mRNA induction and a simultaneous increase in levels of secreted CXCL2 protein. Our results demonstrate that expression of CoV spike proteins induces ER stress, which could subsequently trigger innate immune responses. However, at that point in infection, translation of host mRNA is already severely reduced in infected cells, preventing the synthesis of CXCL2 and ER stress proteins despite their increased mRNA concentrations.",,"['Versteeg, Gijs A.', 'van de Nes, Paula S.', 'Bredenbeek, Peter J.', 'Spaan, Willy J. M.']",,,,
,PMC,Enhancement of Murine Coronavirus Replication by Severe Acute Respiratory Syndrome Coronavirus Protein 6 Requires the N-Terminal Hydrophobic Region but Not C-Terminal Sorting Motifs,http://dx.doi.org/10.1128/JVI.01308-07,PMC2045524,,,"Severe acute respiratory syndrome coronavirus encodes several accessory proteins of unknown function. We previously showed that one such protein, encoded by ORF6, enhanced the growth of mouse hepatitis virus in tissue culture cells and in mice. Protein 6 consists of an N-terminal hydrophobic peptide and a C-terminal region containing intracellular protein sorting motifs. Herein, we show that mutation of the hydrophobic region but not the sorting motifs affected the ability of protein 6 to enhance virus growth. Collectively, these results support the notion that the 6 protein interacts with membrane-bound viral replication or assembly machinery to directly enhance virus replication and virulence in animals.",,"['Netland, Jason', 'Ferraro, Debra', 'Pewe, Lecia', 'Olivares, Heidi', 'Gallagher, Thomas', 'Perlman, Stanley']",,,,
,PMC,Emerging opportunities to prevent occupational lung disease,http://dx.doi.org/10.1136/oem.2006.029918,PMC2078499,,,How to tackle new causes of occupational lung disease over the next decade,,"Kreiss, Kathleen",,,,
,PMC,Expansion of CMAJ's support for health promotion and disease prevention,http://dx.doi.org/10.1503/cmaj.070781,PMC1930180,,,,,"['MacDonald, Noni', 'Weir, Erica', 'Patrick, David', 'Potvin, Louise', 'Scott, Jeff']",,,,
,PMC,"Understanding, compliance and psychological impact of the SARS quarantine experience",http://dx.doi.org/10.1017/S0950268807009156,PMC2870884,,,"This study examines a cohort of persons quarantined during the 2003 SARS outbreak in Canada and describes their understanding of, difficulties and compliance with, and the psychological impact of the quarantine experience. A mailed questionnaire was administered to 1912 eligible adults and included the Impact of Events Scale – Revised (IES-R) to assess symptoms of post-traumatic stress disorder (PTSD). Self-reported compliance with all required quarantine measures was low (15·8±2·3%), although significantly higher when the rationale for quarantine was understood (P=0·018). Health-care workers (HCW) experienced greater psychological distress, including symptoms of PTSD (P<0·001). Increasing perceived difficulty with compliance, HCW, longer quarantine and compliance with quarantine requirements were significant contributors to higher IES-R scores. The low compliance with quarantine requirements introduces concerns about the effectiveness of quarantine as a public health measure. Improvements in compliance and reduced psychological distress may be possible by minimizing duration, revising requirements, and providing enhanced education and support.",,"['REYNOLDS, D.\xa0L.', 'GARAY, J.\xa0R.', 'DEAMOND, S.\xa0L.', 'MORAN, M.\xa0K.', 'GOLD, W.', 'STYRA, R.']",,,,
,PMC,"Molecular cloning, expression, purification and crystallographic analysis of PRRSV 3CL protease",http://dx.doi.org/10.1107/S1744309107033234,PMC2335157,,,"3CL protease, a viral chymotrypsin-like proteolytic enzyme, plays a pivotal role in the transcription and replication machinery of many RNA viruses, including porcine reproductive and respiratory syndrome virus (PRRSV). In this study, the full-length 3CL protease from PRRSV was cloned and overexpressed in Escherichia coli. Crystallization experiments yielded crystals that diffracted to 2.1 Å resolution and belong to space group C2, with unit-cell parameters a = 112.31, b = 48.34, c = 42.88 Å, β = 109.83°. The Matthews coefficient and the solvent content were calculated to be 2.49 Å(3) Da(−1) and 50.61%, respectively, for one molecule in the asymmetric unit.",,"['Tian, Xinsheng', 'Feng, Youjun', 'Zhao, Tiezhu', 'Peng, Hao', 'Yan, Jinghua', 'Qi, Jianxun', 'Jiang, Fan', 'Tian, Kegong', 'Gao, Feng']",,,,
,PMC,"Lost in the World of Functional Genomics, Systems Biology, and Translational Research: Is There Life after the Milstein Award?",http://dx.doi.org/10.1016/j.cytogfr.2007.06.019,PMC1994668,,,"We've always wanted to save the world from the scourges of virus infection by developing better drugs and vaccines. But fully understanding the intricacies of virus-host interactions, the first step in achieving this goal, requires the ability to view the process on a grand scale. The advent of high-throughput technologies, such as DNA microarrays and mass spectrometry, provided the first opportunities to obtain such a view. Here we describe our efforts to use these tools to focus on the changes in cellular gene expression and protein abundance that occur in response to virus infection. By examining these changes in a comprehensive manner, we have been able to discover exciting new insights into innate immunity, interferon and cytokine signaling, and the strategies used by viruses to overcome these cellular defenses. Functional genomics may yet save the world from killer viruses.",,"['Katze, Michael G.', 'Korth, Marcus J.']",,,,
,PMC,Amino Acid Substitutions in the S2 Region Enhance Severe Acute Respiratory Syndrome Coronavirus Infectivity in Rat Angiotensin-Converting Enzyme 2-Expressing Cells,http://dx.doi.org/10.1128/JVI.01143-07,PMC2045470,,,"To clarify the molecular basis of severe acute respiratory syndrome coronavirus (SARS-CoV) adaptation to different host species, we serially passaged SARS-CoV in rat angiotensin-converting enzyme 2 (ACE2)-expressing cells. After 15 passages, the virus (Rat-P15) came to replicate effectively in rat ACE2-expressing cells. Two amino acid substitutions in the S2 region were found on the Rat-P15 S gene. Analyses of the infectivity of the pseudotype-bearing S protein indicated that the two substitutions in the S2 region, especially the S950F substitution, were responsible for efficient infection. Therefore, virus adaptation to different host species can be induced by amino acid substitutions in the S2 region.",,"['Fukushi, Shuetsu', 'Mizutani, Tetsuya', 'Sakai, Kouji', 'Saijo, Masayuki', 'Taguchi, Fumihiro', 'Yokoyama, Masaru', 'Kurane, Ichiro', 'Morikawa, Shigeru']",,,,
,PMC,Single Amino Acid Changes in the Nipah and Hendra Virus Attachment Glycoproteins Distinguish EphrinB2 from EphrinB3 Usage,http://dx.doi.org/10.1128/JVI.00999-07,PMC2045465,,,"The henipaviruses, Nipah virus (NiV) and Hendra virus (HeV), are lethal emerging paramyxoviruses. EphrinB2 and ephrinB3 have been identified as receptors for henipavirus entry. NiV and HeV share similar cellular tropisms and likely use an identical receptor set, although a quantitative comparison of receptor usage by NiV and HeV has not been reported. Here we show that (i) soluble NiV attachment protein G (sNiV-G) bound to cell surface-expressed ephrinB3 with a 30-fold higher affinity than that of sHeV-G, (ii) NiV envelope pseudotyped reporter virus (NiVpp) entered ephrinB3-expressing cells much more efficiently than did HeV pseudotyped particles (HeVpp), and (iii) NiVpp but not HeVpp entry was inhibited efficiently by soluble ephrinB3. These data underscore the finding that NiV uses ephrinB3 more efficiently than does HeV. Henipavirus G chimeric protein analysis implicated residue 507 in the G ectodomain in efficient ephrinB3 usage. Curiously, alternative versions of published HeV-G sequences show variations at residue 507 that can clearly affect ephrinB3 but not ephrinB2 usage. We further defined surrounding mutations (W504A and E505A) that diminished ephrinB3-dependent binding and viral entry without compromising ephrinB2 receptor usage and another mutation (E533Q) that abrogated both ephrinB2 and -B3 usage. Our results suggest that ephrinB2 and -B3 binding determinants on henipavirus G are distinct and dissociable. Global expression analysis showed that ephrinB3, but not ephrinB2, is expressed in the brain stem. Thus, ephrinB3-mediated viral entry and pathology may underlie the severe brain stem neuronal dysfunction seen in fatal Nipah viral encephalitis. Characterizing the determinants of ephrinB2 versus -B3 usage will further our understanding of henipavirus pathogenesis.",,"['Negrete, Oscar A.', 'Chu, David', 'Aguilar, Hector C.', 'Lee, Benhur']",,,,
,PMC,"Universal Precautions in the Era of HIV/AIDS: Perception of Health Service Providers in Yunnan, China",http://dx.doi.org/10.1007/s10461-007-9278-8,PMC2736060,,,"With a rising HIV/AIDS epidemic, it has become especially important for health service providers in China to understand and correctly adhere to universal precautions. Using qualitative interview data, perspectives from both health administrators and service providers working at all levels of China’s health care system were examined. Service providers admitted selective adherence and non-adherence to universal precautions in their daily medical practice, and gave their explanations for such behaviors. Lack of time to put on protective gear, gear’s interference with medical procedures, lack of administrative support, heavy workload in hospitals, inaccurate risk assessment, and beliefs that compliance with universal precautions is unnecessary, time consuming and costly were mentioned as reasons behind noncompliance. Effective universal precaution interventions need to target both administrators and providers, and address both structural barriers and individual attitudinal and behavioral factors.",,"['Wu, Sheng', 'Li, Li', 'Wu, Zunyou', 'Cao, Haijun', 'Lin, Chunqing', 'Yan, Zhihua', 'Jia, Manhong', 'Cui, Haixia']",,,,
,PMC,When individual behaviour matters: homogeneous and network models in epidemiology,http://dx.doi.org/10.1098/rsif.2007.1100,PMC2394553,,,"Heterogeneity in host contact patterns profoundly shapes population-level disease dynamics. Many epidemiological models make simplifying assumptions about the patterns of disease-causing interactions among hosts. In particular, homogeneous-mixing models assume that all hosts have identical rates of disease-causing contacts. In recent years, several network-based approaches have been developed to explicitly model heterogeneity in host contact patterns. Here, we use a network perspective to quantify the extent to which real populations depart from the homogeneous-mixing assumption, in terms of both the underlying network structure and the resulting epidemiological dynamics. We find that human contact patterns are indeed more heterogeneous than assumed by homogeneous-mixing models, but are not as variable as some have speculated. We then evaluate a variety of methodologies for incorporating contact heterogeneity, including network-based models and several modifications to the simple SIR compartmental model. We conclude that the homogeneous-mixing compartmental model is appropriate when host populations are nearly homogeneous, and can be modified effectively for a few classes of non-homogeneous networks. In general, however, network models are more intuitive and accurate for predicting disease spread through heterogeneous host populations.",,"['Bansal, Shweta', 'Grenfell, Bryan T', 'Meyers, Lauren Ancel']",,,,
,PMC,"Design of helical, oligomeric HIV-1 fusion inhibitor peptides with potent activity against enfuvirtide-resistant virus",http://dx.doi.org/10.1073/pnas.0701478104,PMC1937542,,,"Enfuvirtide (ENF), the first approved fusion inhibitor (FI) for HIV, is a 36-aa peptide that acts by binding to the heptad repeat 1 (HR1) region of gp41 and preventing the interaction of the HR1 and HR2 domains, which is required for virus–cell fusion. Treatment-acquired resistance to ENF highlights the need to create FI therapeutics with activity against ENF-resistant viruses and improved durability. Using rational design, we have made a series of oligomeric HR2 peptides with increased helical structure and with exceptionally high HR1/HR2 bundle stability. The engineered peptides are found to be as much as 3,600-fold more active than ENF against viruses that are resistant to the HR2 peptides ENF, T-1249, or T-651. Passaging experiments using one of these peptides could not generate virus with decreased sensitivity, even after >70 days in culture, suggesting superior durability as compared with ENF. In addition, the pharmacokinetic properties of the engineered peptides were improved up to 100-fold. The potent antiviral activity against resistant viruses, the difficulty in generating resistant virus, and the extended half-life in vivo make this class of fusion inhibitor peptide attractive for further development.",,"['Dwyer, John J.', 'Wilson, Karen L.', 'Davison, Donna K.', 'Freel, Stephanie A.', 'Seedorff, Jennifer E.', 'Wring, Stephen A.', 'Tvermoes, Nicolai A.', 'Matthews, Thomas J.', 'Greenberg, Michael L.', 'Delmedico, Mary K.']",,,,
,PMC,Development of Recombinant Nucleoprotein-Based Diagnostic Systems for Lassa Fever,http://dx.doi.org/10.1128/CVI.00101-07,PMC2043324,,,"Diagnostic systems for Lassa fever (LF), a viral hemorrhagic fever caused by Lassa virus (LASV), such as enzyme immunoassays for the detection of LASV antibodies and LASV antigens, were developed using the recombinant nucleoprotein (rNP) of LASV (LASV-rNP). The LASV-rNP was expressed in a recombinant baculovirus system. LASV-rNP was used as an antigen in the detection of LASV-antibodies and as an immunogen for the production of monoclonal antibodies. The LASV-rNP was also expressed in HeLa cells by transfection with the expression vector encoding cDNA of the LASV-NP gene. An immunoglobulin G enzyme-linked immunosorbent assay (ELISA) using LASV-rNP and an indirect immunofluorescence assay using LASV-rNP-expressing HeLa cells were confirmed to have high sensitivity and specificity in the detection of LASV-antibodies. A novel monoclonal antibody to LASV-rNP, monoclonal antibody 4A5, was established. A sandwich antigen capture (Ag-capture) ELISA using the monoclonal antibody and an anti-LASV-rNP rabbit serum as capture and detection antibodies, respectively, was then developed. Authentic LASV nucleoprotein in serum samples collected from hamsters experimentally infected with LASV was detected by the Ag-capture ELISA. The Ag-capture ELISA specifically detected LASV-rNP but not the rNPs of lymphocytic choriomeningitis virus or Junin virus. The sensitivity of the Ag-capture ELISA in detecting LASV antigens was comparable to that of reverse transcription-PCR in detecting LASV RNA. These LASV rNP-based diagnostics were confirmed to be useful in the diagnosis of LF even in institutes without a high containment laboratory, since the antigens can be prepared without manipulation of the infectious viruses.",,"['Saijo, Masayuki', 'Georges-Courbot, Marie-Claude', 'Marianneau, Philippe', 'Romanowski, Victor', 'Fukushi, Shuetsu', 'Mizutani, Tetsuya', 'Georges, Alain-Jean', 'Kurata, Takeshi', 'Kurane, Ichiro', 'Morikawa, Shigeru']",,,,
,PMC,A Functional Ubiquitin-Specific Protease Embedded in the Large Tegument Protein (ORF64) of Murine Gammaherpesvirus 68 Is Active during the Course of Infection,http://dx.doi.org/10.1128/JVI.01149-07,PMC2045495,,,"All herpesviruses contain a ubiquitin (Ub)-specific cysteine protease domain embedded within their large tegument protein, based on homology with the corresponding sequences of UL36 from herpes simplex virus type 1 and M48 from murine cytomegalovirus. This type of activity has yet to be demonstrated for cells infected with a gammaherpesvirus. By activity-based profiling, we show that the large tegument protein of murine gammaherpesvirus (MHV-68) ORF64 (273 kDa) is a functional deubiquitinating protease, as assessed by tandem mass spectrometry of adducts in extracts from MHV-68-infected cells that had been labeled with ubiquitin vinylmethylester, a ubiquitin-based active site-directed probe. The recombinantly expressed amino-terminal segment of ORF64 displays deubiquitinating activity toward Ub C-terminal 7-amido-4-methylcoumarin in vitro. The findings reported here for MHV-68 ORF64 extend those made for the alpha- and betaherpesvirus families and are consistent with an important, conserved enzymatic function of the tegument protein.",,"['Gredmark, Sara', 'Schlieker, Christian', 'Quesada, Victor', 'Spooner, Eric', 'Ploegh, Hidde L.']",,,,
,PMC,Host Cell Cathepsins Potentiate Moloney Murine Leukemia Virus Infection,http://dx.doi.org/10.1128/JVI.02853-06,PMC2045468,,,"The roles of cellular proteases in Moloney murine leukemia virus (MLV) infection were investigated using MLV particles pseudotyped with vesicular stomatitis virus (VSV) G glycoprotein as a control for effects on core MLV particles versus effects specific to Moloney MLV envelope protein (Env). The broad-spectrum inhibitors cathepsin inhibitor III and E-64d gave comparable dose-dependent inhibition of Moloney MLV Env and VSV G pseudotypes, suggesting that the decrease did not involve the envelope protein. Whereas, CA-074 Me gave a biphasic response that differentiated between Moloney MLV Env and VSV G at low concentrations, at which the drug is highly selective for cathepsin B, but was similar for both glycoproteins at higher concentrations, at which CA-074 Me inhibits other cathepsins. Moloney MLV infection was lower on cathepsin B knockout fibroblasts than wild-type cells, whereas VSV G infection was not reduced on the B(−/−) cells. Taken together, these results support the notion that cathepsin B acts at an envelope-dependent step while another cathepsin acts at an envelope-independent step, such as uncoating or viral-DNA synthesis. Virus binding was not affected by CA-074 Me, whereas syncytium induction was inhibited in a dose-dependent manner, consistent with cathepsin B involvement in membrane fusion. Western blot analysis revealed specific cathepsin B cleavage of SU in vitro, while TM and CA remained intact. Infection could be enhanced by preincubation of Moloney MLV with cathepsin B, consistent with SU cleavage potentiating infection. These data suggested that during infection of NIH 3T3 cells, endocytosis brings Moloney MLV to early lysosomes, where the virus encounters cellular proteases, including cathepsin B, that cleave SU.",,"['Kumar, Pankaj', 'Nachagari, Deepa', 'Fields, Carolyn', 'Franks, John', 'Albritton, Lorraine M.']",,,,
,PMC,Processing of Open Reading Frame 1a Replicase Proteins nsp7 to nsp10 in Murine Hepatitis Virus Strain A59 Replication,http://dx.doi.org/10.1128/JVI.00017-07,PMC2045455,,,"Coronaviruses express open reading frame 1a (ORF1a) and ORF1b polyproteins from which 16 nonstructural proteins (nsp) are derived. The highly conserved region at the carboxy terminus of ORF1a is processed by the nsp5 proteinase (M(pro)) into mature products, including nsp7, nsp8, nsp9, and nsp10, proteins with predicted or identified activities involved in RNA synthesis. Although continuous translation and proteolytic processing of ORF1ab by M(pro) is required for replication, it is unknown whether specific cleavage events within the polyprotein are dispensable. We determined the requirement for the nsp7 to nsp10 proteins and their processing during murine hepatitis virus (MHV) replication. Through use of an MHV reverse genetics system, in-frame deletions of the coding sequences for nsp7 to nsp10, or ablation of their flanking M(pro) cleavage sites, were made and the effects upon replication were determined. Viable viruses were characterized by analysis of M(pro) processing, RNA transcription, and growth fitness. Deletion of any of the regions encoding nsp7 to nsp10 was lethal. Disruption of the cleavage sites was lethal with the exception of that of the nsp9-nsp10 site, which resulted in a mutant virus with attenuated replication. Passage of the attenuated nsp9-nsp10 cleavage mutant increased fitness to near-wild-type kinetics without reversion to a virus capable of processing nsp9-nsp10. We also confirmed the presence of a second cleavage site between nsp7 and nsp8. In order to determine whether a distinct function could be attributed to preprocessed forms of the polyprotein, including nsp7 to nsp10, the genes encoding nsp7 and nsp8 were rearranged. The mutant virus was not viable, suggesting that the uncleaved protein may be essential for replication or proteolytic processing.",,"['Deming, Damon J.', 'Graham, Rachel L.', 'Denison, Mark R.', 'Baric, Ralph S.']",,,,
,PMC,Corrections,http://dx.doi.org/10.1529/biophysj.107.0900157,PMC1896228,,,,,,,,,
,PMC,TLR3- and Th2 Cytokine-Dependent Production of Thymic Stromal Lymphopoietin in Human Airway Epithelial Cells,,PMC2220044,,,"Thymic stromal lymphopoietin (TSLP) is elevated in asthma and triggers dendritic cell-mediated activation of Th2 inflammatory responses. Although TSLP has been shown to be produced mainly by airway epithelial cells, the regulation of epithelial TSLP expression has not been extensively studied. We investigated the expression of TSLP in cytokine- or TLR ligand-treated normal human bronchial epithelial cells (NHBE). The mRNA for TSLP was significantly up-regulated by stimulation with IL-4 (5.5-fold) and IL-13 (5.3-fold), weakly up-regulated by TNF-α, TGF-β, and IFN-β, and not affected by IFN-γ in NHBE. TSLP mRNA was only significantly up-regulated by the TLR3 ligand (dsRNA) among the TLR ligands tested (66.8-fold). TSLP was also induced by in vitro infection with rhinovirus. TSLP protein was detected after stimulation with dsRNA (120 ± 23 pg/ml). The combination of TNF-α and IL-4 produced detectable levels of TSLP protein (40 ± 13 pg/ml). In addition, TSLP was synergistically enhanced by a combination of IL-4 and dsRNA (mRNA; 207-fold, protein; 325 ± 75 pg/ml). The induction of TSLP by dsRNA was dependent upon NF-κB and IFN regulatory factor 3 (IRF-3) signaling via TLR3 as indicated by a study with small interfering RNA. The potent topical glucocorticoid fluticasone propionate significantly suppressed dsRNA-dependent TSLP production in NHBE. These results suggest that the expression of TSLP is induced in airway epithelial cells by stimulation with the TLR3 ligand and Th2 cytokines and that this response is suppressed by glucocorticoid treatment. This implies that respiratory viral infection and the recruitment of Th2 cytokine producing cells may amplify Th2 inflammation via the induction of TSLP in the asthmatic airway.",,"['Kato, Atsushi', 'Favoreto, Silvio', 'Avila, Pedro C.', 'Schleimer, Robert P.']",,,,
,PMC,The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2,http://dx.doi.org/10.1016/j.virol.2007.04.035,PMC2693060,,,"The cellular receptor for human coronavirus NL63 (HCoV-NL63), a group I coronavirus, is angiotensin-converting enzyme2 (ACE2). ACE2 is also the receptor for the SARS coronavirus (SARS-CoV), a group II coronavirus. Here we describe the ability of HCoV-NL63 to utilize a number of ACE2 variants previously characterized as SARS-CoV receptors. Several ACE2 variants that reduced SARS-CoV S-protein association similarly reduced that of HCoV-NL63, whereas alteration of a number of solvent-exposed ACE2 residues did not interfere with binding by either S protein. One notable exception is ACE2 residue 354, at the boundary of the SARS-CoV binding site, whose alteration markedly inhibited utilization by the HCoV-NL63 but not SARS-CoV S proteins. In addition, the SARS-CoV S-protein receptor-binding domain inhibited entry mediated by the HCoV-NL63 S protein. These studies indicate that HCoV-NL63, like SARS-CoV, associates region of human ACE2 that includes a key loop formed by β-strands 4 and 5.",,"['Li, Wenhui', 'Sui, Jianhua', 'Huang, I-Chueh', 'Kuhn, Jens H.', 'Radoshitzky, Sheli R.', 'Marasco, Wayne A.', 'Choe, Hyeryun', 'Farzan, Michael']",,,,
,PMC,A Sabin 1 poliovirus-based vaccine vector transfects Vero cells with high efficiency,http://dx.doi.org/10.1007/s10616-007-9085-0,PMC2267503,,,"Over the past 40 years, live oral poliovirus (PV) vaccines have contributed to the eradication of wild PV in most countries. These live vaccine strains have a high safety record and can stimulate both cellular and humoral immune responses. As both of these factors are critical characteristics of a good vaccine, we aimed to modify the oral PV vaccines to create a powerful vaccine vector for extraneous antigen expression. In this study, we amplified three separate fragments from the Sabin 1 virus genome by RT-PCR and cloned them into the pGEM-TEasy vector. A cassette containing engineered protease cleavage sites and a polylinker was introduced into one of these fragments (f1) in front of the translation start site. This construction facilitated the insertion of foreign genes into the vector and the subsequent release of their co-translated antigens after digestion by endogenous protease. We also placed a ribozyme (Rz) sequence between the T7 promoter and viral genomic DNA so that in vitro transcription and Rz cleavage recreated the authentic 5′ end of the PV genome RNA. Poly(A)(40) tails were added to the 3′ end of the genome to stabilize the transcribed RNA. The three PV genome fragments and their derivatives were cloned into various types of vectors that were transfected into Vero cells. Virus rescue experiments demonstrated that both the Rz and poly(A)(40 )elements were required for high transfection efficiency of the vector-derived RNAs.",,"['Li, Changgui', 'Han, Wei', 'Zhang, Yingqi', 'Wang, Junzhi']",,,,
,PMC,Role of Endocytosis and Low pH in Murine Hepatitis Virus Strain A59 Cell Entry,http://dx.doi.org/10.1128/JVI.00725-07,PMC2045462,,,"Infection by the coronavirus mouse hepatitis virus strain A59 (MHV-A59) requires the release of the viral genome by fusion with the respective target membrane of the host cell. Fusion is mediated by the viral S protein. Here, the entry pathway of MHV-A59 into murine fibroblast cells was studied by independent approaches. Infection of cells assessed by plaque reduction assay was strongly inhibited by lysosomotropic compounds and substances that interfere with clathrin-dependent endocytosis, suggesting that MHV-A59 is taken up via endocytosis and delivered to acidic endosomal compartments. Infection was only slightly reduced in the presence of substances inhibiting proteases of endosomal compartments, precluding that the endocytic uptake is required to activate the fusion potential of the S protein by its cleavage. Fluorescence confocal microscopy of labeled MHV-A59 confirmed that virus is taken up via endocytosis. Bright labeling of intracellular compartments suggests their fusion with the viral envelope. No fusion with the plasma membrane was observed at neutral pH conditions. However, when virus was bound to cells and the pH was lowered to 5.0, we observed a strong labeling of the plasma membrane. Electron microscopy revealed low pH triggered conformational alterations of the S ectodomain. Very likely, these alterations are irreversible because low-pH treatment of viruses in the absence of target membranes caused an irreversible loss of the fusion activity. The results imply that endocytosis plays a major role in MHV-A59 infection and the acidic pH of the endosomal compartment triggers a conformational change of the S protein mediating fusion.",,"['Eifart, Patricia', 'Ludwig, Kai', 'Böttcher, Christoph', 'de Haan, Cornelis A. M.', 'Rottier, Peter J. M.', 'Korte, Thomas', 'Herrmann, Andreas']",,,,
,PMC,Arterivirus Subgenomic mRNA Synthesis and Virion Biogenesis Depend on the Multifunctional nsp1 Autoprotease,http://dx.doi.org/10.1128/JVI.00683-07,PMC2045461,,,"Many groups of plus-stranded RNA viruses produce additional, subgenomic mRNAs to regulate the expression of part of their genome. Arteriviruses and coronaviruses (order Nidovirales) are unique among plus-stranded RNA viruses for using a mechanism of discontinuous RNA synthesis to produce a nested set of 5′- and 3′-coterminal subgenomic mRNAs, which serve to express the viral structural protein genes. The discontinuous step presumably occurs during minus-strand synthesis and joins noncontiguous sequences copied from the 3′- and 5′-proximal domains of the genomic template. Nidovirus genome amplification (“replication”) and subgenomic mRNA synthesis (“transcription”) are driven by 13 to 16 nonstructural proteins (nsp's), generated by autocatalytic processing of two large “replicase” polyproteins. Previously, using a replicon system, the N-terminal nsp1 replicase subunit of the arterivirus equine arteritis virus (EAV) was found to be dispensable for replication but crucial for transcription. Using reverse genetics, we have now addressed the role of nsp1 against the background of the complete EAV life cycle. Mutagenesis revealed that nsp1 is in fact a multifunctional regulatory protein. Its papain-like autoprotease domain releases nsp1 from the replicase polyproteins, a cleavage essential for viral RNA synthesis. Several mutations in the putative N-terminal zinc finger domain of nsp1 selectively abolished transcription, while replication was either not affected or even increased. Other nsp1 mutations did not significantly affect either replication or transcription but still dramatically reduced the production of infectious progeny. Thus, nsp1 is involved in at least three consecutive key processes in the EAV life cycle: replicase polyprotein processing, transcription, and virion biogenesis.",,"['Tijms, Marieke A.', 'Nedialkova, Danny D.', 'Zevenhoven-Dobbe, Jessika C.', 'Gorbalenya, Alexander E.', 'Snijder, Eric J.']",,,,
,PMC,Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies,http://dx.doi.org/10.1073/pnas.0701000104,PMC1924550,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) caused a worldwide epidemic in late 2002/early 2003 and a second outbreak in the winter of 2003/2004 by an independent animal-to-human transmission. The GD03 strain, which was isolated from an index patient of the second outbreak, was reported to resist neutralization by the human monoclonal antibodies (hmAbs) 80R and S3.1, which can potently neutralize isolates from the first outbreak. Here we report that two hmAbs, m396 and S230.15, potently neutralized GD03 and representative isolates from the first SARS outbreak (Urbani, Tor2) and from palm civets (SZ3, SZ16). These antibodies also protected mice challenged with the Urbani or recombinant viruses bearing the GD03 and SZ16 spike (S) glycoproteins. Both antibodies competed with the SARS-CoV receptor, ACE2, for binding to the receptor-binding domain (RBD), suggesting a mechanism of neutralization that involves interference with the SARS-CoV–ACE2 interaction. Two putative hot-spot residues in the RBD (Ile-489 and Tyr-491) were identified within the SARS-CoV spike that likely contribute to most of the m396-binding energy. Residues Ile-489 and Tyr-491 are highly conserved within the SARS-CoV spike, indicating a possible mechanism of the m396 cross-reactivity. Sequence analysis and mutagenesis data show that m396 might neutralize all zoonotic and epidemic SARS-CoV isolates with known sequences, except strains derived from bats. These antibodies exhibit cross-reactivity against isolates from the two SARS outbreaks and palm civets and could have potential applications for diagnosis, prophylaxis, and treatment of SARS-CoV infections.",,"['Zhu, Zhongyu', 'Chakraborti, Samitabh', 'He, Yuxian', 'Roberts, Anjeanette', 'Sheahan, Tim', 'Xiao, Xiaodong', 'Hensley, Lisa E.', 'Prabakaran, Ponraj', 'Rockx, Barry', 'Sidorov, Igor A.', 'Corti, Davide', 'Vogel, Leatrice', 'Feng, Yang', 'Kim, Jae-Ouk', 'Wang, Lin-Fa', 'Baric, Ralph', 'Lanzavecchia, Antonio', 'Curtis, Kristopher M.', 'Nabel, Gary J.', 'Subbarao, Kanta', 'Jiang, Shibo', 'Dimitrov, Dimiter S.']",,,,
,PMC,“Alternative” Endocytic Mechanisms Exploited by Pathogens: New Avenues for Therapeutic Delivery?,http://dx.doi.org/10.1016/j.addr.2007.06.009,PMC2040389,,,"Some pathogens utilize unique routes to enter cells that may evade the intracellular barriers encountered by the typical clathrin-mediated endocytic pathway. Retrograde transport and caveolar uptake are among the better characterized pathways, as alternatives to clathrin-mediated endocytosis, that are known to facilitate entry of pathogens and potential delivery agents. Recent characterization of the trafficking mechanisms of prion proteins and certain bacteria may present new paradigms for strategizing improvements in therapeutic spread and retention of therapy. This review will provide an overview of such endocytic pathways, and discuss current and future possibilities in using these routes as a means to improve therapeutic delivery.",,"Medina-Kauwe, Lali K.",,,,
,PMC,Alpha-beta T cells provide protection against lethal encephalitis in the murine model of VEEV infection,http://dx.doi.org/10.1016/j.virol.2007.05.041,PMC2067255,,,"We evaluated the safety and immunogenicity of a chimeric alphavirus vaccine candidate in mice with selective immunodeficiencies. This vaccine candidate was highly attenuated in mice with deficiencies in the B and T cell compartments, as well as in mice with deficient gamma-interferon responsiveness. However, the level of protection varied among the strains tested. Wild type mice were protected against lethal VEEV challenge. In contrast, alpha/beta (αβ) TCR-deficient mice developed lethal encephalitis following VEEV challenge, while mice deficient in gamma/delta ( γδ) T cells were protected. Surprisingly, the vaccine potency was diminished by 50% in animals lacking interferon-gamma receptor alpha chain (R1)-chain and a minority of vaccinated immunoglobulin heavy chain-deficient (μMT) mice survived challenge, which suggests that neutralizing antibody may not be absolutely required for protection. Prolonged replication of encephalitic VEEV in the brain of pre-immunized mice is not lethal and adoptive transfer experiments indicate that CD3(+) T cells are required for protection.",,"['Paessler, Slobodan', 'Yun, Nadezhda E.', 'Judy, Barbara M.', 'Dziuba, Natallia', 'Zacks, Michele A.', 'Grund, Anna H.', 'Frolov, Ilya', 'Campbell, Gerald A.', 'Weaver, Scott C.', 'Estes, D. Mark']",,,,
,PMC,Probing the Interaction between Feline Immunodeficiency Virus and CD134 by Using the Novel Monoclonal Antibody 7D6 and the CD134 (O×40) Ligand,http://dx.doi.org/10.1128/JVI.01020-07,PMC2045395,,,"The feline immunodeficiency virus (FIV) targets activated CD4-positive helper T cells preferentially, inducing an AIDS-like immunodeficiency in its natural host species, the domestic cat. The primary receptor for FIV is CD134, a member of the tumor necrosis factor receptor superfamily, and all primary viral strains tested to date use CD134 for infection. We examined the expression of CD134 in the cat using a novel anti-feline CD134 monoclonal antibody (MAb), 7D6, and showed that as in rats and humans, CD134 expression is restricted tightly to CD4(+), and not CD8(+), T cells, consistent with the selective targeting of these cells by FIV. However, FIV is also macrophage tropic, and in chronic infection the viral tropism broadens to include B cells and CD8(+) T cells. Using 7D6, we revealed CD134 expression on a B220-positive (B-cell) population and on cultured macrophages but not peripheral blood monocytes. Moreover, macrophage CD134 expression and FIV infection were enhanced by activation in response to bacterial lipopolysaccharide. Consistent with CD134 expression on human and murine T cells, feline CD134 was abundant on mitogen-stimulated CD4(+) T cells, with weaker expression on CD8(+) T cells, concordant with the expansion of FIV into CD8(+) T cells with progression of the infection. The interaction between FIV and CD134 was probed using MAb 7D6 and soluble CD134 ligand (CD134L), revealing strain-specific differences in sensitivity to both 7D6 and CD134L. Infection with isolates such as PPR and B2542 was inhibited well by both 7D6 and CD134L, suggesting a lower affinity of interaction. In contrast, GL8, CPG, and NCSU were relatively refractory to inhibition by both 7D6 and CD134L and, accordingly, may have a higher-affinity interaction with CD134, permitting infection of cells where CD134 levels are limiting.",,"['Willett, Brian J.', 'McMonagle, Elizabeth L.', 'Logan, Nicola', 'Spiller, O. Brad', 'Schneider, Pascal', 'Hosie, Margaret J.']",,,,
,PMC,Regulation of Hepatitis B Virus Replication by the Phosphatidylinositol 3-Kinase-Akt Signal Transduction Pathway,http://dx.doi.org/10.1128/JVI.00541-07,PMC2045390,,,"The phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway is one of the major oncogenic pathways and is activated in many types of human cancers, including hepatocellular carcinoma. It can also be activated by the hepatitis C virus (HCV) nonstructural 5A (NS5A) protein. In the present study, we set out to determine the regulatory effects of this pathway on the replication of hepatitis B virus (HBV). Our results demonstrate that the expression of a constitutively active Akt1 profoundly inhibited HBV RNA transcription and consequently reduced HBV DNA replication in HepG2 cells. This suppression of HBV gene transcription was apparently mediated by the activation of mTOR, as it was abolished by the mTOR inhibitor rapamycin. Moreover, treatment of HBV-expressing HepG2.2.15 cells with inhibitors of PI3K, Akt, and mTOR increased the transcription of 3.5-kb and 2.4-kb viral RNA as well as the replication of HBV DNA. This observation implies that the basal level activation of this pathway in HepG2 cells regulated HBV replication. Consistent with previous reports showing that the HCV NS5A protein could bind to the p85 subunit of PI3K and activate the PI3K-Akt signal transduction pathway, our results showed that expression of this protein could inhibit HBV RNA transcription and reduce HBV DNA replication in HepG2 cells. Taken together, our results suggest that the activation of the PI3K-Akt pathway during liver oncogenesis may be at least partially responsible for the elimination of HBV replication from tumor cells and may also provide an explanation for the observed suppression of HBV replication by HCV coinfection.",,"['Guo, Haitao', 'Zhou, Tianlun', 'Jiang, Dong', 'Cuconati, Andrea', 'Xiao, Guang-Hui', 'Block, Timothy M.', 'Guo, Ju-Tao']",,,,
,PMC,Stable trichimerism after marrow grafting from 2 DLA-identical canine donors and nonmyeloablative conditioning,http://dx.doi.org/10.1182/blood-2007-02-071282,PMC1896124,,,"Although hematopoietic cell transplantation (HCT) is generally accomplished using a single donor, multiple donors have been used to enhance the speed of engraftment, particularly in the case of umbilical cord blood grafts. Here we posed the question in the canine HCT model whether stable dual-donor chimerism could be established using 2 DLA-identical donors. We identified 8 DLA-identical littermate triplets in which the marrow recipients received 2 Gy total body irradiation followed by marrow infusions from 2 donors and postgrafting immunosuppression. All 8 dogs showed initial “trichimerism,” which was sustained in 5 dogs, while 2 dogs rejected one of the allografts and remained mixed chimeras, and 1 dog rejected both allografts. Immune function in one trichimeric dog, as tested by mixed leukocyte culture response and antibody response to sheep red blood cells, was found to be normal. Five dogs received kidney grafts from one of their respective marrow donors at least 6 months after HCT without immunosuppressive drugs, and grafts in 4 dogs are surviving without rejection. In summary, following nonmyeloablative conditioning, simultaneous administration of marrow grafts from 2 DLA-identical littermates could result in sustained trichimerism, and immunologic tolerance could include a kidney graft from one of the marrow donors.",,"['Graves, Scott S.', 'Hogan, William', 'Kuhr, Christian S.', 'Diaconescu, Razvan', 'Harkey, Michael A.', 'Georges, George E.', 'Sale, George E.', 'Zellmer, Eustacia', 'Baran, Szczepan', 'Jochum, Christoph', 'Stone, Brad', 'Storb, Rainer']",,,,
,PMC,CD13/APN regulates endothelial invasion and filopodia formation,http://dx.doi.org/10.1182/blood-2006-02-002931,PMC1896108,,,"CD13/aminopeptidase N is a transmembrane peptidase that is induced in the vasculature of solid tumors and is a potent angiogenic regulator. Here, we demonstrate that CD13 controls endothelial cell invasion in response to the serum peptide bradykinin by facilitating signal transduction at the level of the plasma membrane. Inhibition of CD13 abrogates bradykinin B(2) receptor internalization, leading to the attenuation of downstream events such as bradykinin-induced activation of Cdc42 and filopodia formation, and thus affects endothelial cell motility. Investigation into mechanisms underlying this block led us to focus on B(2)R internalization via membrane-dependent mechanisms. Membrane disruption by depletion of cholesterol or trypsinization halts B(2)R internalization, invasion, and filopodia formation, which can be recovered with addition of cholesterol. However, this functional recovery is severely impaired in the presence of CD13 antagonists, and the distribution of membrane proteins is disordered in treated cells, suggesting a role for CD13 in plasma membrane protein organization. Finally, exogenous expression of wild-type but not mutant CD13 further alters protein distribution, suggesting peptidase activity is required for CD13's regulatory activity. Therefore, CD13 functions as a novel modulator of signal transduction and cell motility via its influence on specific plasma membrane organization, thus regulating angiogenesis.",,"['Petrovic, Nenad', 'Schacke, Wolfgang', 'Gahagan, J. Reed', ""O'Conor, Catherine A."", 'Winnicka, Beata', 'Conway, Rebecca E.', 'Mina-Osorio, Paola', 'Shapiro, Linda H.']",,,,
,PMC,Aberrant activation profile of cytokines and mitogen-activated protein kinases in type 2 diabetic patients with nephropathy,http://dx.doi.org/10.1111/j.1365-2249.2007.03389.x,PMC1942021,,,"Cytokine-induced inflammation is involved in the pathogenesis of type 2 diabetes mellitus (DM). We investigated plasma concentrations and ex vivo production of cytokines and chemokines, and intracellular signalling molecules, mitogen-activated protein kinases (MAPK) in T helper (Th) cells and monocytes in 94 type 2 diabetic patients with or without nephropathy and 20 healthy controls. Plasma concentrations of inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-18 and chemokine CCL2 in patients with diabetic nephropathy (DN) were significantly higher than control subjects, while IL-10, CXCL8, CXCL9, CXCL10 and adiponectin concentrations of DN were significantly higher than patients without diabetic nephropathy (NDN) and control subjects (all P < 0·05). Plasma concentrations of TNF-α, IL-6, IL-10, IL-18, CCL2, CXCL8, CXCL9, CXCL10 and adiponectin exhibited significant positive correlation with urine albumin : creatinine ratio in DN patients. The percentage increases of ex vivo production of IL-6, CXCL8, CXCL10, CCL2 and CCL5 upon TNF-α activation were significantly higher in both NDN and DN patients than controls (all P < 0·05). The percentage increases in IL-18-induced phosphorylation of extracellular signal-regulated kinase (ERK) in Th cells of NDN and DN were significantly higher than controls (P< 0·05), while the percentage increase in TNF-α-induced phosphorylation of p38 MAPK in monocytes and IL-18-induced phosphorylation of p38 MAPK in Th cells and monocytes were significantly higher in NDN patients than controls. These results confirmed that the aberrant production of inflammatory cytokines and chemokines and differential activation of MAPK in different leucocytes are the underlying immunopathological mechanisms of type 2 DM patients with DN.",,"['Wong, C K', 'Ho, A W Y', 'Tong, P C Y', 'Yeung, C Y', 'Kong, A P S', 'Lun, S W M', 'Chan, J C N', 'Lam, C W K']",,,,
,PMC,Atmospheric Movement of Microorganisms in Clouds of Desert Dust and Implications for Human Health,http://dx.doi.org/10.1128/CMR.00039-06,PMC1932751,,,"Billions of tons of desert dust move through the atmosphere each year. The primary source regions, which include the Sahara and Sahel regions of North Africa and the Gobi and Takla Makan regions of Asia, are capable of dispersing significant quantities of desert dust across the traditionally viewed oceanic barriers. While a considerable amount of research by scientists has addressed atmospheric pathways and aerosol chemistry, very few studies to determine the numbers and types of microorganisms transported within these desert dust clouds and the roles that they may play in human health have been conducted. This review is a summary of the current state of knowledge of desert dust microbiology and the health impact that desert dust and its microbial constituents may have in downwind environments both close to and far from their sources.",,"Griffin, Dale W.",,,,
,PMC,The preparedness of emergency medical services against occupationally acquired communicable diseases in the prehospital environment in South Africa,http://dx.doi.org/10.1136/emj.2006.045575,PMC2658403,,,"BACKGROUND: Emergency medical care is performed in an uncontrolled environment and involves invasive procedures and life support measures. The performance of these duties places emergency care practitioners (ECPs) at risk of occupationally acquired injuries and communicable diseases. Although legislative guidelines exist for the protection of healthcare workers, little is known about the protective measures available for and utilised by ECPs in the pre‐hospital environment in South Africa. OBJECTIVES: To review the availability and implementation of emergency medical services (EMS)‐specific infection control policies and standard operating procedures in the pre‐hospital environment. METHODS: Interviews with key informants were used to collect data concerning policies on communicable diseases and infection control in the EMS, the operational aspects of these policies, and educational programmes on communicable diseases and infection control for ECPs. RESULTS: There is no national policy on communicable diseases and infection control in EMS. Only KwaZulu‐Natal, Eastern Cape and Gauteng have EMS‐specific standard operating procedures for communicable diseases and infection control. Formal education and in‐service training is limited. CONCLUSIONS: A national communicable disease and infection control policy specific to the EMS needs to be developed together with an accredited training module on communicable diseases and infection control for EMS in the pre‐hospital environment.",,"['Mahomed, Ozayr', 'Jinabhai, Champaklal Chaganlal', 'Taylor, Myra', 'Yancey, Arthur']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.01117-07,PMC1933363,,,,,,,,,
,PMC,Bird flu: if or when? Planning for the next pandemic,http://dx.doi.org/10.1136/pgmj.2007.059253,PMC2600097,,,"Avian influenza or “bird flu” is causing increasing concern across the world as experts prepare for the possible occurrence of the next human influenza pandemic. Only influenza A has ever been shown to have the capacity to cause pandemics. Currently A/H5N1, a highly pathogenic avian influenza virus, is of particular concern. Outbreaks of this disease in birds, especially domestic poultry, have been detected across Southeast Asia at regular intervals since 2003, and have now affected parts of Africa and Europe. Many unaffected countries across the world are preparing for the possible arrival of HPAI A/H5N1 in wild birds and poultry within their territories. All such countries need to prepare for the rare possibility of a small number of human cases of HPAI A/H5N1, imported through foreign travel. Although it is by no means certain that HPAI A/H5N1 will be the source of the next pandemic, many countries are also preparing for the inevitable occurrence of human pandemic influenza.",,"['Sellwood, Chloe', 'Asgari‐Jirhandeh, Nima', 'Salimee, Sultan']",,,,
,PMC,Crystallographic studies of the complexes of antiviral protein griffithsin with glucose and N-acetylglucosamine,http://dx.doi.org/10.1110/ps.072889407,PMC2206701,,,"Crystal structures of complexes of an antiviral lectin griffithsin (GRFT) with glucose and N-acetylglucosamine were solved and refined at high resolution. In both complexes, all six monosaccharide-binding sites of GRFT were occupied and the mode of binding was similar to that of mannose. In our previous attempts to obtain a complex with N-acetylglucosamine by soaking, only a single site was occupied; thus, cocrystallization was clearly superior despite lower concentration of the ligand. Isothermal titration calorimetric experiments with N-acetylglucosamine, glucose, and mannose provided enthalpic evidence of distinct binding differences between the three monosaccharides. A comparison of the mode of binding of different monosaccharides is discussed in the context of the antiviral activity of GRFT, based on specific binding to high-mannose-containing complex carbohydrates found on viral envelopes.",,"['Ziółkowska, Natasza E.', 'Shenoy, Shilpa R.', ""O'Keefe, Barry R."", 'Wlodawer, Alexander']",,,,
,PMC,Contrasting Experiences of State Public Health Law Reform Pursuant to the Turning Point Model State Public Health Act,,PMC1888509,,,,,"['Meier, Benjamin Mason', 'Gebbie, Kristine M.', 'Hodge, James G.']",,,,
,PMC,Risk factors associated with superspreading events in SARS,,PMC2117241,,,,,"Mohammed, Ali A",,,,
,PMC,Type IVB Pilus Operon Promoter Controlling Expression of the Severe Acute Respiratory Syndrome-Associated Coronavirus Nucleocapsid Gene in Salmonella enterica Serovar Typhi Elicits Full Immune Response by Intranasal Vaccination,http://dx.doi.org/10.1128/CVI.00076-07,PMC2044483,,,"Attenuated Salmonella enterica serovar Typhi strains have been considered to be attractive as potential live oral delivery vector vaccines because of their ability to elicit the full array of immune responses in humans. In this study, we constructed an attenuated S. enterica serovar Typhi strain stably expressing conserved nucleocapsid (N) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) by integrating the N gene into the pilV gene, which was under the control of the type IVB pilus operon promoter in S. enterica serovar Typhi. BALB/c mice were immunized with this recombinant strain through different routes: intranasally, orogastrically, intraperitoneally, and intravenously. Results showed that the intranasal route caused the highest production of specific immunoglobulin G (IgG), IgG2a, and secretory IgA, where IgG2a was imprinted as a Th1 cell bias. Moreover, this recombinant live vaccine induced significantly high levels of specific cytotoxic T-lymphocyte activities and increased gamma interferon-producing T cells compared with the parental strain. Our work provides insights into how the type IVB pilus operon promoter controlling SARS-CoV N gene expression in Salmonella might be attractive for a live-vector vaccine against SRAS-CoV infection, for it could induce mucosal, humoral, and cellular immune responses. Our work also indicates that the type IVB pilus operon promoter controlling foreign gene expression in Salmonella can elicit full immune responses by intranasal vaccination.",,"['Luo, Fengling', 'Feng, Yong', 'Liu, Min', 'Li, Pingfei', 'Pan, Qin', 'Jeza, Victor Tunje', 'Xia, Bing', 'Wu, Jianguo', 'Zhang, Xiao-Lian']",,,,
,PMC,Development of a Respiratory Virus Panel Test for Detection of Twenty Human Respiratory Viruses by Use of Multiplex PCR and a Fluid Microbead-Based Assay,http://dx.doi.org/10.1128/JCM.02436-06,PMC2045291,,,"Virology laboratories historically have used direct fluorescent-antibody assay (DFA) and culture to detect six or seven respiratory viruses. Following the discovery of five new human respiratory viruses since 2000, there is an increasing need for diagnostic tests to detect these emerging viruses. We have developed a new test that can detect 20 different respiratory virus types/subtypes in a single 5-h test. The assay employs multiplex PCR using 14 virus-specific primer pairs, followed by a multiplexed target-specific primer extension (TSPE) reaction using 21 primers for specific respiratory virus types and subtypes. TSPE products were sorted and identified by using a fluid microsphere-based array (Universal Array; TmBioscience Corporation, Toronto, Canada) and the Luminex x-MAP system. The assay detected influenza A and B viruses; influenza A virus subtypes H1, H3, and H5 (including subtype H5N1 of the Asian lineage); parainfluenza virus types 1, 2, 3, and 4; respiratory syncytial virus types A and B; adenovirus; metapneumovirus; rhinovirus; enterovirus; and coronaviruses OC43, 229E, severe acute respiratory syndrome coronavirus, NL63, and HKU1. In a prospective evaluation using 294 nasopharyngeal swab specimens, DFA/culture detected 119 positives and the respiratory virus panel (RVP) test detected 112 positives, for a sensitivity of 97%. The RVP test detected an additional 61 positive specimens that either were not detected by DFA/culture or were positive for viruses not tested for by DFA/culture. After resolution of discordant results by using a second unique PCR assay and by using a combined reference standard of positivity, the RVP test detected 180 of 183 true positives, for a sensitivity of 98.5%, whereas DFA and culture detected only 126 of 183 true positives, for a sensitivity of 68.8%. The RVP test should improve the capabilities of hospital and public health laboratories for diagnosing viral respiratory tract infections and should assist public health agencies in identifying etiologic agents in respiratory tract infection outbreaks.",,"['Mahony, J.', 'Chong, S.', 'Merante, F.', 'Yaghoubian, S.', 'Sinha, T.', 'Lisle, C.', 'Janeczko, R.']",,,,
,PMC,MultiCode-PLx System for Multiplexed Detection of Seventeen Respiratory Viruses,http://dx.doi.org/10.1128/JCM.00669-07,PMC2045250,,,"The MultiCode-PLx system (EraGen Biosciences, Inc., Madison, WI) for the detection of respiratory viruses uses an expanded genetic alphabet, multiplex PCR chemistry, and microsphere flow cytometry to rapidly detect and specifically identify 17 different respiratory viruses directly in clinical specimens. The MultiCode-PLx system was tested in parallel with direct fluorescent-antibody (DFA) staining and rapid shell vial culture (R-mix cells; Diagnostic Hybrids, Inc. Athens, OH) with 354 respiratory specimens from adult patients that were submitted to the clinical virology laboratory at the Emory University Hospital. Single-target PCRs were performed with retained samples to confirm the positive results obtained with the MultiCode-PLx system for viruses not covered by DFA and R-mix culture (metapneumovirus, coronaviruses [CoV], parainfluenza viruses 4a and 4b, and rhinoviruses) and to resolve any discrepancies between the DFA and R-mix culture and the MultiCode-PLx results for viruses common to both systems. Respiratory viruses were detected in 77 (21.8%) and 116 (32.7%) specimens by DFA and R-mix culture and with the MultiCode-PLx system, respectively. Among the viruses common to both systems, the MultiCode-PLx system detected significantly more influenza A viruses (P = 0.0026). An additional increased diagnostic yield with the MultiCode-PLx system resulted from the detection of human metapneumovirus (HMPV) in 9 specimens, human CoV (HCoV) in 3 specimens, and human rhinovirus (HRV) in 16 specimens. Also, two mixed viral infections were detected by the MultiCode-PLx system (HCoV OC43 and HRV infections and HMPV and HRV infections), but none were detected by DFA and R-mix culture. Single-target PCRs verified the results obtained with the MultiCode-PLx system for 73 of 81 (90.1%) specimens that had discordant results or that were not covered by DFA and R-mix culture. The MultiCode-PLx system provides clinical laboratories with a practical, rapid, and sensitive means for the massively multiplexed molecular detection of common respiratory viruses.",,"['Nolte, Frederick S.', 'Marshall, David J.', 'Rasberry, Christopher', 'Schievelbein, Sabina', 'Banks, Grier G.', 'Storch, Gregory A.', 'Arens, Max Q.', 'Buller, Richard S.', 'Prudent, James R.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus ORF6 Antagonizes STAT1 Function by Sequestering Nuclear Import Factors on the Rough Endoplasmic Reticulum/Golgi Membrane,http://dx.doi.org/10.1128/JVI.01012-07,PMC2045396,,,"The host innate immune response is an important deterrent of severe viral infection in humans and animals. Nuclear import factors function as key gatekeepers that regulate the transport of innate immune regulatory cargo to the nucleus of cells to activate the antiviral response. Using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model, we demonstrate that SARS-COV ORF6 protein is localized to the endoplasmic reticulum (ER)/Golgi membrane in infected cells, where it binds to and disrupts nuclear import complex formation by tethering karyopherin alpha 2 and karyopherin beta 1 to the membrane. Retention of import factors at the ER/Golgi membrane leads to a loss of STAT1 transport into the nucleus in response to interferon signaling, thus blocking the expression of STAT1-activated genes that establish an antiviral state. We mapped the region of ORF6, which binds karyopherin alpha 2, to the C terminus of ORF6 and show that mutations in the C terminus no longer bind karyopherin alpha 2 or block the nuclear import of STAT1. We also show that N-terminal deletions of karyopherin alpha 2 that no longer bind to karyopherin beta 1 still retain ORF6 binding activity but no longer block STAT1 nuclear import. Recombinant SARS-CoV lacking ORF6 did not tether karyopherin alpha 2 to the ER/Golgi membrane and allowed the import of the STAT1 complex into the nucleus. We discuss the likely implications of these data on SARS-CoV replication and pathogenesis.",,"['Frieman, Matthew', 'Yount, Boyd', 'Heise, Mark', 'Kopecky-Bromberg, Sarah A.', 'Palese, Peter', 'Baric, Ralph S.']",,,,
,PMC,A previously unknown reovirus of bat origin is associated with an acute respiratory disease in humans,http://dx.doi.org/10.1073/pnas.0701372104,PMC1899191,,,"Respiratory infections constitute the most widespread human infectious disease, and a substantial proportion of them are caused by unknown etiological agents. Reoviruses (respiratory enteric orphan viruses) were first isolated from humans in the early 1950s and so named because they were not associated with any known disease. Here, we report a previously unknown reovirus (named “Melaka virus”) isolated from a 39-year-old male patient in Melaka, Malaysia, who was suffering from high fever and acute respiratory disease at the time of virus isolation. Two of his family members developed similar symptoms ≈1 week later and had serological evidence of infection with the same virus. Epidemiological tracing revealed that the family was exposed to a bat in the house ≈1 week before the onset of the father's clinical symptoms. Genome sequence analysis indicated a close genetic relationship between Melaka virus and Pulau virus, a reovirus isolated in 1999 from fruit bats in Tioman Island, Malaysia. Screening of sera collected from human volunteers on the island revealed that 14 of 109 (13%) were positive for both Pulau and Melaka viruses. This is the first report of an orthoreovirus in association with acute human respiratory diseases. Melaka virus is serologically not related to the different types of mammalian reoviruses that were known to infect humans asymptomatically. These data indicate that bat-borne reoviruses can be transmitted to and cause clinical diseases in humans.",,"['Chua, Kaw Bing', 'Crameri, Gary', 'Hyatt, Alex', 'Yu, Meng', 'Tompang, Mohd Rosli', 'Rosli, Juliana', 'McEachern, Jennifer', 'Crameri, Sandra', 'Kumarasamy, Verasingam', 'Eaton, Bryan T.', 'Wang, Lin-Fa']",,,,
,PMC,"Vaccinia Virus Entry, Exit, and Interaction with Differentiated Human Airway Epithelia",http://dx.doi.org/10.1128/JVI.00601-07,PMC2045410,,,"Variola virus, the causative agent of smallpox, enters and exits the host via the respiratory route. To better understand the pathogenesis of poxvirus infection and its interaction with respiratory epithelia, we used vaccinia virus and examined its interaction with primary cultures of well-differentiated human airway epithelia. We found that vaccinia virus preferentially infected the epithelia through the basolateral membrane and released viral progeny across the apical membrane. Despite infection and virus production, epithelia retained tight junctions, transepithelial electrical conductance, and a steep transepithelial concentration gradient of virus, indicating integrity of the epithelial barrier. In fact, during the first four days of infection, epithelial height and cell number increased. These morphological changes and maintenance of epithelial integrity required vaccinia virus growth factor, which was released basolaterally, where it activated epidermal growth factor 1 receptors. These data suggest a complex interaction between the virus and differentiated airway epithelia; the virus preferentially enters the cells basolaterally, exits apically, and maintains epithelial integrity by stimulating growth factor receptors.",,"['Vermeer, Paola D.', 'McHugh, Julia', 'Rokhlina, Tatiana', 'Vermeer, Daniel W.', 'Zabner, Joseph', 'Welsh, Michael J.']",,,,
,PMC,An RNA Pseudoknot in the 3′ End of the Arterivirus Genome Has a Critical Role in Regulating Viral RNA Synthesis,http://dx.doi.org/10.1128/JVI.00747-07,PMC1951461,,,"In the life cycle of plus-strand RNA viruses, the genome initially serves as the template for both translation of the viral replicase gene and synthesis of minus-strand RNA and is ultimately packaged into progeny virions. These various processes must be properly balanced to ensure efficient viral proliferation. To achieve this, higher-order RNA structures near the termini of a variety of RNA virus genomes are thought to play a key role in regulating the specificity and efficiency of viral RNA synthesis. In this study, we have analyzed the signals for minus-strand RNA synthesis in the prototype of the arterivirus family, equine arteritis virus (EAV). Using site-directed mutagenesis and an EAV reverse genetics system, we have demonstrated that a stem-loop structure near the 3′ terminus of the EAV genome is required for RNA synthesis. We have also obtained evidence for an essential pseudoknot interaction between the loop region of this stem-loop structure and an upstream hairpin residing in the gene encoding the nucleocapsid protein. We propose that the formation of this pseudoknot interaction may constitute a molecular switch that could regulate the specificity or timing of viral RNA synthesis. This hypothesis is supported by the fact that phylogenetic analysis predicted the formation of similar pseudoknot interactions near the 3′ end of all known arterivirus genomes, suggesting that this interaction has been conserved in evolution.",,"['Beerens, Nancy', 'Snijder, Eric J.']",,,,
,PMC,Antibody Recognition of Cell Surface-Associated NS1 Triggers Fc-γ Receptor-Mediated Phagocytosis and Clearance of West Nile Virus-Infected Cells,http://dx.doi.org/10.1128/JVI.00879-07,PMC1951387,,,"Previous studies have suggested that monoclonal antibodies (MAbs) to flavivirus nonstructural protein-1 (NS-1) protect against infection in mice through an Fc-γ receptor-dependent pathway. To identify a specific mechanism, we evaluated the protective activity of anti-NS1 MAbs to WNV using mice and cells with deficiencies of specific Fc-γ receptors. Our results suggest that only MAbs that recognize cell surface-associated NS1 trigger Fc-γ receptor I- and/or IV-mediated phagocytosis and clearance of WNV-infected cells. These findings may be relevant for generating novel therapeutic MAbs or vaccines against flaviviruses that target the NS1 protein.",,"['Chung, Kyung Min', 'Thompson, Bruce S.', 'Fremont, Daved H.', 'Diamond, Michael S.']",,,,
,PMC,Reflections on SARS,http://dx.doi.org/10.1503/cmaj.070308,PMC1891123,,,,,"Weir, Erica",,,,
,PMC,Effect of widespread restrictions on the use of hospital services during an outbreak of severe acute respiratory syndrome,http://dx.doi.org/10.1503/cmaj.061174,PMC1891122,,,"BACKGROUND: Restrictions on the nonurgent use of hospital services were imposed in March 2003 to control an outbreak of severe acute respiratory syndrome (SARS) in Toronto, Ont. We describe the impact of these restrictions on health care utilization and suggest lessons for future epidemics. METHODS: We performed a retrospective population-based study of the Greater Toronto Area (hereafter referred to as Toronto) and unaffected comparison regions (Ottawa and London, Ont.) before, during and after the SARS outbreak (April 2001–March 2004). We determined the adjusted rates of hospital admissions, emergency department and outpatient visits, diagnostic testing and drug prescribing. RESULTS: During the early and late SARS restriction periods, the rate of overall and medical admissions decreased by 10%–12% in Toronto; there was no change in the comparison regions. The rate of elective surgery in Toronto fell by 22% and 15% during the early and late restriction periods respectively and by 8% in the comparison regions. The admission rates for urgent surgery remained unchanged in all regions; those for some acute serious medical conditions decreased by 15%–21%. The rates of elective cardiac procedures declined by up to 66% in Toronto and by 71% in the comparison regions; the rates of urgent and semi-urgent procedures declined little or increased. High-acuity visits to emergency departments fell by 37% in Toronto, and inter-hospital patient transfers fell by 44% in the circum-Toronto area. Drug prescribing and primary care visits were unchanged in all regions. INTERPRETATION: The restrictions achieved modest reductions in overall hospital admissions and substantial reductions in the use of elective services. Brief reductions occurred in admissions for some acute serious conditions, high-acuity visits to emergency departments and inter-hospital patient transfers suggesting that access to care for some potentially seriously ill patients was affected.",,"['Schull, Michael J.', 'Stukel, Thérèse A.', 'Vermeulen, Marian J.', 'Zwarenstein, Merrick', 'Alter, David A.', 'Manuel, Douglas G.', 'Guttmann, Astrid', 'Laupacis, Andreas', 'Schwartz, Brian']",,,,
,PMC,Highlights of this issue,,PMC1891120,,,,,,,,,
,PMC,Is the Quarantine Act relevant?,http://dx.doi.org/10.1503/cmaj.070130,PMC1891118,,,,,"Schabas, Richard",,,,
,PMC,Viruses as anticancer drugs,http://dx.doi.org/10.1016/j.tips.2007.05.005,PMC3125087,,,"Oncolytic viruses are being developed as anticancer drugs. They propagate selectively in tumor tissue and destroy it without causing excessive damage to normal non-cancerous tissues. When used as drugs, they must meet stringent criteria for safety and efficacy and be amenable to pharmacological study in human subjects. Specificity for neoplastic tissue is the key to safety, and this goal can be achieved through a variety of ingenious virus-engineering strategies. Antiviral immunity remains a significant barrier to the clinical efficacy of oncolytic viruses but this is being addressed by using novel immune-evasive delivery strategies and immunosuppressive drugs. Noninvasive pharmacokinetic monitoring is facilitated by engineering marker genes into the viral genome. Clinical data on the pharmacokinetics of oncolytic viruses will be the key to accelerating their development and approval as effective anticancer drugs. This review introduces concepts relevant to the use of viruses as anticancer drugs, emphasizing targeting mechanisms as well as safety and efficacy issues that are currently limiting their clinical success.",,"['Russell, Stephen J.', 'Peng, Kah-Whye']",,,,
,PMC,New regulations aim to prevent international health emergencies,http://dx.doi.org/10.1136/bmj.39241.666829.DB,PMC1892507,,,,,"Moszynski, Peter",,,,
,PMC,Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination,http://dx.doi.org/10.1073/pnas.0703766104,PMC1904174,,,"Capable of inducing antigen-specific immune responses in both systemic and mucosal compartments without the use of syringe and needle, mucosal vaccination is considered ideal for the global control of infectious diseases. In this study, we developed a rice-based oral vaccine expressing cholera toxin B subunit (CTB) under the control of the endosperm-specific expression promoter 2.3-kb glutelin GluB-1 with codon usage optimization for expression in rice seed. An average of 30 μg of CTB per seed was stored in the protein bodies, which are storage organelles in rice. When mucosally fed, rice seeds expressing CTB were taken up by the M cells covering the Peyer's patches and induced CTB-specific serum IgG and mucosal IgA antibodies with neutralizing activity. When expressed in rice, CTB was protected from pepsin digestion in vitro. Rice-expressed CTB also remained stable and thus maintained immunogenicity at room temperature for >1.5 years, meaning that antigen-specific mucosal immune responses were induced at much lower doses than were necessary with purified recombinant CTB. Because they require neither refrigeration (cold-chain management) nor a needle, these rice-based mucosal vaccines offer a highly practical and cost-effective strategy for orally vaccinating large populations against mucosal infections, including those that may result from an act of bioterrorism.",,"['Nochi, Tomonori', 'Takagi, Hidenori', 'Yuki, Yoshikazu', 'Yang, Lijun', 'Masumura, Takehiro', 'Mejima, Mio', 'Nakanishi, Ushio', 'Matsumura, Akiko', 'Uozumi, Akihiro', 'Hiroi, Takachika', 'Morita, Shigeto', 'Tanaka, Kunisuke', 'Takaiwa, Fumio', 'Kiyono, Hiroshi']",,,,
,PMC,Differential activation of polymorphisms of the formyl peptide receptor by formyl peptides,http://dx.doi.org/10.1016/j.bbadis.2007.06.001,PMC2094211,,,"We have investigated the role of two polymorphic sites (R190W and N192K) on the binding and activation of the formyl peptide receptor (FPR) by viral and formyl peptides. WEDWVGWI, a peptide with antiviral activity derived from the membrane proximal region of feline immunodeficiency virus, binds with high affinity to FPR. The three tryptophans in the peptide are all essential for FPR binding, just as they were essential for antiviral activity (Giannecchini, S. et al., J. Virol. 77 (2003) 3724). Formyl-NleWEDWVGWI behaved as a weak partial agonist with FPR W190/N192 but a stronger partial agonist with FPR R190/K192 and FPR R190/N192. Formyl-NleNleWEDWVGWI behaved as a full agonist toward all three FPRs but exhibited a much higher EC(50) with W190/N192 FPR (300±45 nM) than for R190/K192 FPR (40±3 nM) or R190/N192 (60±8 nM). Formyl-MYKWPWYVWL preferentially activated R190/K192 and R190/N192 FPRs by >5 fold compared to W190/N192 FPR. Formyl-MFEDAVAWF, a peptide derived from a protein in Mycobacterium avium subsp. paratuberculosis and formyl-MFTFEPFPTN, a peptide derived from the N-terminus of chemotaxis inhibitory protein of Staphylococcus aureus with an added N-terminal methionine exhibited the greatest selectivity for R190/K192 and R190/N192 FPRs with ~10 fold lower EC(50S) than that observed with FPR W190/N192. Thus, individuals with the W190 polymorphism may display a reduced ability to detect certain formyl peptides.",,"Mills, John S.",,,,
,PMC,Effectiveness of control measures during the SARS epidemic in Beijing: a comparison of the R(t) curve and the epidemic curve,http://dx.doi.org/10.1017/S0950268807008722,PMC2870828,,,"One of the areas most affected by SARS was Beijing with 2521 reported cases. We estimate the effective reproductive number R(t) for the Beijing SARS epidemic, which represents the average number of secondary cases per primary case on each day of the epidemic and is therefore a measure of the underlying transmission dynamics. Our results provide a quantitative assessment of the effectiveness of public health control measures. More generally, our results illustrate how changes in R(t) will reflect changes in the epidemic curve.",,"['COWLING, B.\xa0J.', 'HO, L.\xa0M.', 'LEUNG, G.\xa0M.']",,,,
,PMC,First Isolation of Cytopathogenic Bovine Torovirus in Cell Culture from a Calf with Diarrhea,http://dx.doi.org/10.1128/CVI.00475-06,PMC2044491,,,"A cytopathogenic virus (designated the Aichi/2004 strain) was isolated in a human rectal adenocarcinoma cell line (HRT-18) from the ileum contents of a calf with diarrhea. Oval and elongated particles, approximately 100 to 170 nm in diameter, with club-shaped projections were seen in the infected culture supernatant, and torovirus-like (tubular and torus nucleocapsid) structures were seen in the infected cells by electron microscopy. An antiserum against bovine torovirus (BToV) reacted with the infected cells by immunofluorescence and neutralized the isolate. However, antisera against bovine coronavirus (BCV) failed to react with the infected cells by immunofluorescence or did not neutralize the isolate. Further, the isolate was positive for BToV by reverse transcription-PCR (RT-PCR) targeting fragments of the nucleocapsid (N), membrane (M), and spike (S) genes. Comparison of the nucleotide sequences of the PCR products with those of the published N, M, and S genes (476 to 497, 672, and 687 to 690 nucleotides, respectively) of toroviruses showed high sequence identities (up to 99.4%, 98.7%, and 94.9% for the N, M, and S genes, respectively) between the isolate and BToVs. In contrast, the isolate was negative for BCV by RT-PCR. In a serological survey of serum samples from 355 calves at 33 farms, 92% of calves were positive for neutralizing antibodies to the isolate. These results indicate that the isolate in this study was BToV and that BToV infection might be common in cattle in Japan. To our knowledge, this is the first isolation of BToV in tissue culture.",,"['Kuwabara, Masaki', 'Wada, Kazumasa', 'Maeda, Yukiko', 'Miyazaki, Ayako', 'Tsunemitsu, Hiroshi']",,,,
,PMC,Strategies for Improving Influenza Immunization Rates among Hard-to-Reach Populations,http://dx.doi.org/10.1007/s11524-007-9197-z,PMC2219560,,,"Whereas considerable attention has been devoted to achieving high levels of influenza immunization, the importance of this issue is magnified by concern over pandemic influenza. Most recommendations for vaccine administration address high risk groups such as the elderly and those with chronic diseases, but coverage for hard-to-reach (HTR) populations has had less attention. HTR populations include minorities but also include other primarily urban groups such as undocumented immigrants, substance users, the homeless, and homebound elderly. Obstacles to the provision of immunization to HTR populations are present at the patient, provider, and structural levels. Strategies at the individual level for increasing immunization coverage include community-based educational campaigns to improve attitudes and increase motivation for receiving vaccine; at the provider level, education of providers to encourage immunizations, improving patient–provider interactions, broadening the provider base to include additional nurses and pharmacists, and adoption of standing orders for immunization administration; and at the structural level, promoting wider availability of and access to vaccine. The planning process for an influenza pandemic should include community engagement and extension of strategies beyond traditional providers to involve community-based organizations addressing HTR populations.",,"['Vlahov, David', 'Coady, Micaela H.', 'Ompad, Danielle C.', 'Galea, Sandro']",,,,
,PMC,Detection of Respiratory Viruses and Subtype Identification of Influenza A Viruses by GreeneChipResp Oligonucleotide Microarray,http://dx.doi.org/10.1128/JCM.00737-07,PMC1951265,,,"Acute respiratory infections are significant causes of morbidity, mortality, and economic burden worldwide. An accurate, early differential diagnosis may alter individual clinical management as well as facilitate the recognition of outbreaks that have implications for public health. Here we report on the establishment and validation of a comprehensive and sensitive microarray system for detection of respiratory viruses and subtyping of influenza viruses in clinical materials. Implementation of a set of influenza virus enrichment primers facilitated subtyping of influenza A viruses through the differential recognition of hemagglutinins 1 through 16 and neuraminidases 1 through 9. Twenty-one different respiratory virus species were accurately characterized, including a recently identified novel genetic clade of rhinovirus.",,"['Quan, Phenix-Lan', 'Palacios, Gustavo', 'Jabado, Omar J.', 'Conlan, Sean', 'Hirschberg, David L.', 'Pozo, Francisco', 'Jack, Philippa J. M.', 'Cisterna, Daniel', 'Renwick, Neil', 'Hui, Jeffrey', 'Drysdale, Andrew', 'Amos-Ritchie, Rachel', 'Baumeister, Elsa', 'Savy, Vilma', 'Lager, Kelly M.', 'Richt, Jürgen A.', 'Boyle, David B.', 'García-Sastre, Adolfo', 'Casas, Inmaculada', 'Perez-Breña, Pilar', 'Briese, Thomas', 'Lipkin, W. Ian']",,,,
,PMC,Environment Determines Fidelity for an RNA Virus Replicase,http://dx.doi.org/10.1128/JVI.00587-07,PMC1951419,,,"The rate of insertion and deletion mutations of the replicase of Cucumber mosaic virus (CMV) was determined in planta by using a parasitic satellite RNA (satRNA) as a reporter. We found that the CMV replicase had different fidelity in different environments, with important implications in viral disease evolution. Insertions were very rare events, irrespective of the region of the satRNA genome assayed and independent of the hosts tested. On the other hand, deletion events were more frequent but were restricted to a highly structured region of the reporter. Deletion mutation rates were different for the two hosts tested, although the mutation distribution was not influenced by the hosts. Moreover, hot spots with high mutation rates were identified on the satRNA genome.",,"['Pita, Justin S.', 'de Miranda, Joachim R.', 'Schneider, William L.', 'Roossinck, Marilyn J.']",,,,
,PMC,N-Linked Glycosylation Attenuates H3N2 Influenza Viruses,http://dx.doi.org/10.1128/JVI.00769-07,PMC1951338,,,"Over the last four decades, H3N2 subtype influenza A viruses have gradually acquired additional potential sites for glycosylation within the globular head of the hemagglutinin (HA) protein. Here, we have examined the biological effect of additional glycosylation on the virulence of H3N2 influenza viruses. We created otherwise isogenic reassortant viruses by site-directed mutagenesis that contain additional potential sites for glycosylation and examined the effect on virulence in naïve BALB/c, C57BL/6, and surfactant protein D (SP-D)-deficient mice. The introduction of additional sites was consistent with the sequence of acquisition in the globular head over the past 40 years, beginning with two sites in 1968 to the seven sites found in contemporary influenza viruses circulating in 2000. Decreased morbidity and mortality, as well as lower viral lung titers, were seen in mice as the level of potential glycosylation of the viruses increased. This correlated with decreased evidence of virus-mediated lung damage and increased in vitro inhibition of hemagglutination by SP-D. SP-D-deficient animals displayed an inverse pattern of disease, such that more highly glycosylated viruses elicited disease equivalent to or exceeding that of the wild type. We conclude from these data that increased glycosylation of influenza viruses results in decreased virulence, which is at least partly mediated by SP-D-induced clearance from the lung. The continued exploration of interactions between highly glycosylated viruses and surfactant proteins may lead to an improved understanding of the biology within the lung and strategies for viral control.",,"['Vigerust, David J.', 'Ulett, Kimberly B.', 'Boyd, Kelli L.', 'Madsen, Jens', 'Hawgood, Samuel', 'McCullers, Jonathan A.']",,,,
,PMC,Involvement of host cellular multivesicular body functions in hepatitis B virus budding,http://dx.doi.org/10.1073/pnas.0704000104,PMC1891263,,,"Hepatitis B virus (HBV) is a major human pathogen that chronically infects ≈350 million people, causing liver disease and liver cancer. HBV virions bud into an endoplasmic reticulum (ER)-associated intracellular compartment, but the mechanisms of HBV assembly, budding, and release remain poorly understood. Budding of retroviruses and some other enveloped RNA viruses from plasma membranes requires host functions involved in protein sorting into late endosomal multivesicular bodies (MVBs). To determine whether budding of DNA-containing HBV virions at intracellular membranes also involves MVB functions, we used immunofluorescence to show that, in human hepatoma cells, HBV envelope protein colocalizes with MVB proteins AIP1/ALIX and VPS4B. We also found that a dominant negative (DN) AIP1 mutant inhibited production and/or release of enveloped virions without significant effects on intracellular nucleocapsid formation, whereas DN VPS4B inhibited both nucleocapsid production and budding. By contrast, DN AIP1 and VPS4 had no effect on the efficiency of release of enveloped, nucleocapsid-lacking HBV subviral particles, which are produced in vast excess over virions, and dramatically increased the release of unenveloped, naked nucleocapsids by an apparently nonlytic route. Thus, host MVB functions are required for efficient budding and release of enveloped HBV virions and may be a valuable target for HBV control. Moreover, HBV enveloped virions, enveloped subviral particles, and unenveloped nucleocapsids are all released by distinct pathways with separate host factor requirements.",,"['Watanabe, Tokiko', 'Sorensen, Ericka M.', 'Naito, Akira', 'Schott, Meghan', 'Kim, Seungtaek', 'Ahlquist, Paul']",,,,
,PMC,In silico pharmacology for drug discovery: applications to targets and beyond,http://dx.doi.org/10.1038/sj.bjp.0707306,PMC1978280,,,"Computational (in silico) methods have been developed and widely applied to pharmacology hypothesis development and testing. These in silico methods include databases, quantitative structure-activity relationships, similarity searching, pharmacophores, homology models and other molecular modeling, machine learning, data mining, network analysis tools and data analysis tools that use a computer. Such methods have seen frequent use in the discovery and optimization of novel molecules with affinity to a target, the clarification of absorption, distribution, metabolism, excretion and toxicity properties as well as physicochemical characterization. The first part of this review discussed the methods that have been used for virtual ligand and target-based screening and profiling to predict biological activity. The aim of this second part of the review is to illustrate some of the varied applications of in silico methods for pharmacology in terms of the targets addressed. We will also discuss some of the advantages and disadvantages of in silico methods with respect to in vitro and in vivo methods for pharmacology research. Our conclusion is that the in silico pharmacology paradigm is ongoing and presents a rich array of opportunities that will assist in expediating the discovery of new targets, and ultimately lead to compounds with predicted biological activity for these novel targets.",,"['Ekins, S', 'Mestres, J', 'Testa, B']",,,,
,PMC,Viral RNA extraction for in-the-field analysis,http://dx.doi.org/10.1016/j.jviromet.2007.04.006,PMC3635480,,,"Retroviruses encode their genetic information with RNA molecules, and have a high genomic recombination rate which allows them to mutate more rapidly, thereby posting a higher risk to humans. One important way to help combat a pandemic of viral infectious diseases is early detection before large scale outbreaks occur. The polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR) have been used to identify precisely different strains of some very closely related pathogens. However, isolation and detection of viral RNA in the field are difficult due to the unstable nature of viral RNA molecules. Consequently, performing in-the-field nucleic acid analysis to monitor the spread of viruses is financially and technologically challenging in remote and underdeveloped regions that are high-risk areas for outbreaks. A simplified rapid viral RNA extraction method is reported to meet the requirements for in-the-field viral RNA extraction and detection. The ability of this device to perform viral RNA extraction with subsequent RT-PCR detection of retrovirus is demonstrated. This inexpensive device has the potential to be distributed on a large scale to underdeveloped regions for early detection of retrovirus, with the possibility of reducing viral pandemic events.",,"['Zhong, Jiang F.', 'Weiner, Leslie P.', 'Burke, Kathy', 'Taylor, Clive R.']",,,,
,PMC,A Resampling-Based Test to Detect Person-To-Person Transmission of Infectious Disease,http://dx.doi.org/10.1214/07-AOAS105,PMC2680309,,,"Early detection of person-to-person transmission of emerging infectious diseases such as avian influenza is crucial for containing pandemics. We developed a simple permutation test and its refined version for this purpose. A simulation study shows that the refined permutation test is as powerful as or outcompetes the conventional test built on asymptotic theory, especially when the sample size is small. In addition, our resampling methods can be applied to a broad range of problems where an asymptotic test is not available or fails. We also found that decent statistical power could be attained with just a small number of cases, if the disease is moderately transmissible between humans.",,"['Yang, Yang', 'Longini, Ira M.', 'Halloran, M. Elizabeth']",,,,
,PMC,New rules on international public health security,http://dx.doi.org/10.2471/BLT.07.100607,PMC2636345,,,"A new set of rules on how WHO’s 193 Member States will handle disease outbreaks and other emergencies that could have international public health implications enter into force this month. The International Health Regulations (IHR) were revised in 2005 and have since been published in all six official United Nations’ languages. Now the onus is on countries to implement the regulations. But in order to do this, they need to build their own capacity to detect, assess, notify and report “events”, which may be a disease outbreak, a chemical spill or an unusually high number of deaths in a community. Countries also need to build capacity to respond to public health risks and emergencies of international concern within their borders, such as containing an outbreak. In this interview, Dr Guénaël Rodier, director of International Health Regulations Coordination, describes the challenges that Member States face as they prepare to take on their new responsibilities.",,,,,,
,PMC,Combined distemper-adenoviral pneumonia in a dog,,PMC1876197,,,"A 3 1/2-month-old pug with oculonasal discharge and seizures was submitted for postmortem examination. Grossly, the lungs had cranioventral consolidation, and microscopically, 2 distinct types of inclusion bodies compatible with Canine distemper virus and Canine adenovirus type 2. Presence of both viruses was confirmed via immunohistochemical staining.",,"['Rodriguez-Tovar, Luis E.', 'Ramírez-Romero, Rafael', 'Valdez-Nava, Yazel', 'Nevárez-Garza, Alicia M.', 'Zárate-Ramos, Juan J.', 'López, Alfonso']",,,,
,PMC,"Unreliable Tests, Unreliable Laboratories: Who Needs Them?",,PMC2080531,,,,,"Calisher, Charles H.",,,,
,PMC,Real-Time PCR: Revolutionizing Detection and Expression Analysis of Genes,,PMC2430684,,,"Invention of polymerase chain reaction (PCR) technology by Kary Mullis in 1984 gave birth to real-time PCR. Real-time PCR — detection and expression analysis of gene(s) in real-time — has revolutionized the 21(st) century biological science due to its tremendous application in quantitative genotyping, genetic variation of inter and intra organisms, early diagnosis of disease, forensic, to name a few. We comprehensively review various aspects of real-time PCR, including technological refinement and application in all scientific fields ranging from medical to environmental issues, and to plant.",,"['Deepak, SA', 'Kottapalli, KR', 'Rakwal, R', 'Oros, G', 'Rangappa, KS', 'Iwahashi, H', 'Masuo, Y', 'Agrawal, GK']",,,,
,PMC,"Inevitable or avoidable? Despite the lessons of history, the world is not yet ready to face the next great plague",http://dx.doi.org/10.1038/sj.embor.7400987,PMC2002527,,,,,"Hunter, Philip",,,,
,PMC,High Frequency of Mutations That Expand the Host Range of an RNA Virus,http://dx.doi.org/10.1534/genetics.106.064634,PMC1894571,,,"The ability of a virus population to colonize a novel host is predicted to depend on the equilibrium frequency of potential colonists (i.e., genotypes capable of infecting the novel host) in the source population. In this study, we investigated the determinants of the equilibrium frequency of potential colonists in the RNA bacteriophage φ6. We isolated 40 spontaneous mutants capable of infecting a novel Pseudomonas syringae host and sequenced their host attachment genes to identify the responsible mutations. We observed 16 different mutations in the host attachment gene and used a new statistical approach to estimate that 39 additional mutations were missed by our screen. Phenotypic and fitness assays confirmed that the proximate mechanism underlying host range expansion was an increase in the ability to attach to the novel host and that acquisition of this ability most often imposed a cost for growth rate on two standard hosts. Considered in a population genetic framework, our data suggest that host range mutations should exist in phage populations at an equilibrium frequency (3 × 10(−4)) that exceeds the phage mutation rate by more than two orders of magnitude. Thus, colonization of novel hosts is unlikely to be limited by an inability to produce appropriate mutations.",,"['Ferris, Martin T.', 'Joyce, Paul', 'Burch, Christina L.']",,,,
,PMC,Genomic RNA sequence of feline coronavirus strain FCoV C1Je,http://dx.doi.org/10.1016/j.jfms.2006.12.002,PMC2582377,17363313,NO-CC CODE,"This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV). Viral RNA was isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP). A consensus sequence of the jejunum-derived genomic RNA (FCoV C1Je) was determined from overlapping cDNA fragments produced by reverse transcriptase polymerase chain reaction (RT-PCR) amplification. RT-PCR products were sequenced by a reiterative sequencing strategy and the genomic RNA termini were determined using a rapid amplification of cDNA ends PCR strategy. The FCoV C1Je genome was found to be 29,255 nucleotides in length, excluding the poly(A) tail. Comparison of the FCoV C1Je genomic RNA sequence with that of the laboratory strain FCoV FIP virus (FIPV) 79-1146 showed that both viruses have a similar genome organisation and predictions made for the open reading frames and cis-acting elements of the FIPV 79-1146 genome hold true for FCoV C1Je. In addition, the sequence of the 3′-proximal third of the liver derived genomic RNA (FCoV C1Li), which encompasses the structural and accessory protein genes of the virus, was also determined. Comparisons of the enteric (jejunum) and non-enteric (liver) derived viral RNA sequences revealed 100% nucleotide identity, a finding that questions the well accepted ‘internal mutation theory’ of FIPV pathogenicity.",2007 Jun,"['Dye, Charlotte', 'Siddell, Stuart G.']",J Feline Med Surg,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00833-07,PMC1900128,,,,,,,,,
,PMC,Viral Proteomics,http://dx.doi.org/10.1128/MMBR.00042-06,PMC1899879,,,"Summary: Viruses have long been studied not only for their pathology and associated disease but also as model systems for molecular processes and as tools for identifying important cellular regulatory proteins and pathways. Recent advances in mass spectrometry methods coupled with the development of proteomic approaches have greatly facilitated the detection of virion components, protein interactions in infected cells, and virally induced changes in the cellular proteome, resulting in a more comprehensive understanding of viral infection. In addition, a rapidly increasing number of high-resolution structures for viral proteins have provided valuable information on the mechanism of action of these proteins as well as aided in the design and understanding of specific inhibitors that could be used in antiviral therapies. In this paper, we discuss proteomic studies conducted on all eukaryotic viruses and bacteriophages, covering virion composition, viral protein structures, virus-virus and virus-host protein interactions, and changes in the cellular proteome upon viral infection.",,"['Maxwell, Karen L.', 'Frappier, Lori']",,,,
,PMC,Working with Médecins‐Sans‐Frontières in China: a personal account,http://dx.doi.org/10.1136/sti.2006.023994,PMC2659107,,,A genitourinary medicine trainee's experience of delivering HIV care in China,,"Loke, Wai Ching",,,,
,PMC,Gene Expression Changes in Peripheral Blood Mononuclear Cells during Measles Virus Infection,http://dx.doi.org/10.1128/CVI.00031-07,PMC1951064,,,"Measles virus continues to cause morbidity and mortality despite the existence of a safe and efficacious vaccine. Measles is associated with induction of both a long-lived protective immune response and immunosuppression. To gain insight into immunological changes during measles virus infection, we examined gene expression in blood mononuclear cells from children with acute measles and children in the convalescent phase compared to uninfected control children. There were 13 significantly upregulated and 206 downregulated genes. Upregulated genes included the immune regulatory molecules interleukin 1β (IL-1β), CIAS-1, tumor necrosis factor alpha, PDE4B, PTGS2, IL-8, CXCL2, CCL4, ICAM-1, CD83, GOS-2, IER3 (IEX-1), and TNFAIP3 (A20). Plasma levels of IL-1β and IL-8 were elevated during measles virus infection. Downregulated genes mainly involved three gene ontology biological processes, transcription, signal transduction, and the immune response, and included IL-16 and cell surface receptors IL-4R, IL-6R, IL-7R, IL-27RA, CCR2, and CCR7. Most mRNAs had not returned to control values 1 month after discharge, consistent with prolonged immune response abnormalities during measles virus infection.",,"['Zilliox, Michael J.', 'Moss, William J.', 'Griffin, Diane E.']",,,,
,PMC,"High-Throughput, Sensitive, and Accurate Multiplex PCR-Microsphere Flow Cytometry System for Large-Scale Comprehensive Detection of Respiratory Viruses",http://dx.doi.org/10.1128/JCM.02501-06,PMC1951217,,,"Human respiratory viruses are a diverse group of pathogens composed of hundreds of virus strains, and this presents a major challenge for diagnostic laboratories. To efficiently detect numerous viruses in a large epidemiologic study, we developed a fast, multitarget, sensitive, and specific assay named the Respiratory MultiCode-PLx Assay (RMA). The RMA utilizes improved multiplex PCR chemistry (EraGen MultiCode-PLx technology) coupled with high-throughput microsphere flow cytometry (Luminex). Eighteen sets of virus-specific multiplex PCR primers were developed based on the conserved sequences of all available respiratory-virus sequences for eight distinct groups: human rhinovirus (HRV), respiratory syncytial virus (RSV), parainfluenza virus (PIV), influenza virus (InfV), metapneumovirus, adenovirus (Ad), coronavirus, and enterovirus. Each primer set detected 20 cDNA copies of the intended target per sample and had no reaction with 60,000 copies of human genomic DNA. The accuracy and sensitivity of the RMA for detecting respiratory viruses in human samples were tested with two sets of clinical specimens. First, 101 nasal-wash specimens that were positive for HRV, RSV, InfV, PIV, or Ad by traditional techniques were reanalyzed by RMA, and all target viruses were detected with an overall sensitivity of 94% and specificity of 99%. Second, 103 nasal-wash samples from 5-year-old children with asthma and respiratory symptoms were analyzed; RMA detected viruses in 74 specimens (71.8%) compared to only 24 (23.3%) by traditional culture and immunofluorescent-staining techniques. These results show that RMA is an accurate, sensitive, and practical test for respiratory-virus infections.",,"['Lee, Wai-Ming', 'Grindle, Kris', 'Pappas, Tressa', 'Marshall, David J.', 'Moser, Michael J.', 'Beaty, Edward L.', 'Shult, Peter A.', 'Prudent, James R.', 'Gern, James E.']",,,,
,PMC,Interferon-Mediated Immunopathological Events Are Associated with Atypical Innate and Adaptive Immune Responses in Patients with Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1128/JVI.00527-07,PMC1951379,,,"It is not understood how immune inflammation influences the pathogenesis of severe acute respiratory syndrome (SARS). One area of strong controversy is the role of interferon (IFN) responses in the natural history of SARS. The fact that the majority of SARS patients recover after relatively moderate illness suggests that the prevailing notion of deficient type I IFN-mediated immunity, with hypercytokinemia driving a poor clinical course, is oversimplified. We used proteomic and genomic technology to systematically analyze host innate and adaptive immune responses of 40 clinically well-described patients with SARS during discrete phases of illness from the onset of symptoms to discharge or a fatal outcome. A novel signature of high IFN-α, IFN-γ, and IFN-stimulated chemokine levels, plus robust antiviral IFN-stimulated gene (ISG) expression, accompanied early SARS sequelae. As acute illness progressed, SARS patients entered a crisis phase linked to oxygen saturation profiles. The majority of SARS patients resolved IFN responses at crisis and expressed adaptive immune genes. In contrast, patients with poor outcomes showed deviated ISG and immunoglobulin gene expression levels, persistent chemokine levels, and deficient anti-SARS spike antibody production. We contend that unregulated IFN responses during acute-phase SARS may culminate in a malfunction of the switch from innate immunity to adaptive immunity. The potential for the use of the gene signatures we describe in this study to better assess the immunopathology and clinical management of severe viral infections, such as SARS and avian influenza (H5N1), is therefore worth careful examination.",,"['Cameron, Mark J.', 'Ran, Longsi', 'Xu, Luoling', 'Danesh, Ali', 'Bermejo-Martin, Jesus F.', 'Cameron, Cheryl M.', 'Muller, Matthew P.', 'Gold, Wayne L.', 'Richardson, Susan E.', 'Poutanen, Susan M.', 'Willey, Barbara M.', 'DeVries, Mark E.', 'Fang, Yuan', 'Seneviratne, Charit', 'Bosinger, Steven E.', 'Persad, Desmond', 'Wilkinson, Peter', 'Greller, Larry D.', 'Somogyi, Roland', 'Humar, Atul', 'Keshavjee, Shaf', 'Louie, Marie', 'Loeb, Mark B.', 'Brunton, James', 'McGeer, Allison J.', None, 'Kelvin, David J.']",,,,
,PMC,Characterization of Rift Valley Fever Virus Transcriptional Terminations,http://dx.doi.org/10.1128/JVI.02641-06,PMC1951372,,,"Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) has a tripartite negative-strand genome and causes a mosquito-borne disease among humans and livestock in sub-Saharan African and Arabian Peninsula countries. Phlebovirus L, M, and N mRNAs are synthesized from the virus-sense RNA segments, while NSs mRNA is transcribed from the anti-virus-sense S segment. The present study determined the 3′ termini of all RVFV mRNAs. The 3′ termini of N and NSs mRNAs were mapped within the S-segment intergenic region and were complementary to each other by 30 to 60 nucleotides. The termini of M and L mRNAs were mapped within 122 to 107 nucleotides and 16 to 41 nucleotides, respectively, from the 5′ ends of their templates. Viral RNA elements that control phlebovirus transcriptional terminations are largely unknown. Our studies suggested the importance of a pentanucleotide sequence, CGUCG, for N, NSs, and M mRNA transcription terminations. Homopolymeric tracts of C sequences, which were located upstream of the pentanucleotide sequence, promoted N and M mRNA terminations. Likewise, the homopolymeric tracts of G sequences that are found upstream of the pentanucleotide sequence promoted NSs mRNA termination. The L-segment 5′-untranslated region (L-5′ UTR) had neither the pentanucleotide sequence nor homopolymeric sequences, yet replacement of the S-segment intergenic region with the L-5′ UTR exerted N mRNA termination in an infectious virus. The L-5′ UTR contained two 13-nucleotide-long complete complementary sequences, and their sequence complementarities were important for L mRNA termination. A computer-mediated RNA secondary structure analysis further suggested that RNA secondary structures formed by the sections of the two 13-nucleotide-long sequences and by the sequence between them may have a role in L mRNA termination. Our data demonstrated that viral RNA elements that govern L mRNA termination differed from those that regulate mRNA terminations in the M and S segments.",,"['Ikegami, Tetsuro', 'Won, Sungyong', 'Peters, C. J.', 'Makino, Shinji']",,,,
,PMC,De Novo Initiation of RNA Synthesis by the Arterivirus RNA-Dependent RNA Polymerase,http://dx.doi.org/10.1128/JVI.00564-07,PMC1951334,,,"All plus-strand RNA viruses encode an RNA-dependent RNA polymerase (RdRp) that functions as the catalytic subunit of the viral replication/transcription complex, directing viral RNA synthesis in concert with other viral proteins and, sometimes, host proteins. RNA synthesis essentially can be initiated by two different mechanisms, de novo initiation and primer-dependent initiation. Most viral RdRps have been identified solely on the basis of comparative sequence analysis, and for many viruses the mechanism of initiation is unknown. In this study, using the family prototype equine arteritis virus (EAV), we address the mechanism of initiation of RNA synthesis in arteriviruses. The RdRp domains of the members of the arterivirus family, which are part of replicase subunit nsp9, were compared to coronavirus RdRps that belong to the same order of Nidovirales, as well as to other RdRps with known initiation mechanisms and three-dimensional structures. We report here the first successful expression and purification of an arterivirus RdRp that is catalytically active in the absence of other viral or cellular proteins. The EAV nsp9/RdRp initiates RNA synthesis by a de novo mechanism on homopolymeric templates in a template-specific manner. In addition, the requirements for initiation of RNA synthesis from the 3′ end of the viral genome were studied in vivo using a reverse genetics approach. These studies suggest that the 3′-terminal nucleotides of the EAV genome play a critical role in viral RNA synthesis.",,"['Beerens, Nancy', 'Selisko, Barbara', 'Ricagno, Stefano', 'Imbert, Isabelle', 'van der Zanden, Linda', 'Snijder, Eric J.', 'Canard, Bruno']",,,,
,PMC,"Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens",http://dx.doi.org/10.1073/pnas.0703584104,PMC1887550,,,"The international outbreak of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) in 2002–2003 highlighted the need to develop pretested human vaccine vectors that can be used in a rapid response against newly emerging pathogens. We evaluated Newcastle disease virus (NDV), an avian paramyxovirus that is highly attenuated in primates, as a topical respiratory vaccine vector with SARS-CoV as a test pathogen. Complete recombinant NDV was engineered to express the SARS-CoV spike S glycoprotein, the viral neutralization and major protective antigen, from an added transcriptional unit. African green monkeys immunized through the respiratory tract with two doses of the vaccine developed a titer of SARS-CoV-neutralizing antibodies comparable with the robust secondary response observed in animals that have been immunized with a different experimental SARS-CoV vaccine and challenged with SARS-CoV. When animals immunized with NDV expressing S were challenged with a high dose of SARS-CoV, direct viral assay of lung tissues taken by necropsy at the peak of viral replication demonstrated a 236- or 1,102-fold (depending on the NDV vector construct) mean reduction in pulmonary SARS-CoV titer compared with control animals. NDV has the potential for further development as a pretested, highly attenuated, intranasal vector to be available for expedited vaccine development for humans, who generally lack preexisting immunity against NDV.",,"['DiNapoli, Joshua M.', 'Kotelkin, Alexander', 'Yang, Lijuan', 'Elankumaran, Subbiah', 'Murphy, Brian R.', 'Samal, Siba K.', 'Collins, Peter L.', 'Bukreyev, Alexander']",,,,
,PMC,Identification of Nonessential Regions of the nsp2 Replicase Protein of Porcine Reproductive and Respiratory Syndrome Virus Strain VR-2332 for Replication in Cell Culture,http://dx.doi.org/10.1128/JVI.00562-07,PMC2045381,,,"The nonstructural protein 2 (nsp2) of porcine reproductive and respiratory syndrome virus (PRRSV) is a multidomain protein and has been shown to undergo remarkable genetic variation, primarily in its middle region, while exhibiting high conservation in the N-terminal putative protease domain and the C-terminal predicted transmembrane region. A reverse genetics system of PRRSV North American prototype VR-2332 was developed to explore the importance of different regions of nsp2 for viral replication. A series of mutants with in-frame deletions in the nsp2 coding region were engineered, and infectious viruses were subsequently recovered from transfected cells and further characterized. The results demonstrated that the cysteine protease domain (PL2), the PL2 downstream flanking sequence (amino acids [aa] 181 to 323), and the putative transmembrane domain were critical for replication. In contrast, the segment of nsp2 preceding the PL2 domain (aa 13 to 35) was dispensable for viral replication, and the nsp2 middle hypervariable region (aa 324 to 813) tolerated 100-aa or 200-aa deletions but could not be removed as a whole; the largest deletion was about 400 aa (nsp2Δ324-726). Characterization of the mutants demonstrated that those with small deletions possessed growth kinetics and RNA expression profiles similar to those of the parental virus, while the nsp2Δ324-726 mutant displayed decreased cytolytic activity on MARC-145 cells and did not develop visible plaques. Finally, the utilization of the genetic flexibility of nsp2 to express foreign genes was examined by inserting the gene encoding green fluorescent protein (GFP) in frame into one nsp2 deletion mutant construct. The recombinant virus was viable but impaired and unstable and gradually gained parental growth kinetics by the loss of most of the GFP gene.",,"['Han, Jun', 'Liu, Gongping', 'Wang, Yue', 'Faaberg, Kay S.']",,,,
,PMC,Clathrin-Dependent Entry of Severe Acute Respiratory Syndrome Coronavirus into Target Cells Expressing ACE2 with the Cytoplasmic Tail Deleted,http://dx.doi.org/10.1128/JVI.00253-07,PMC1951348,,,"The penetration of various viruses into host cells is accomplished by hijacking the host endocytosis machinery. In the case of severe acute respiratory syndrome coronavirus (SARS-CoV) infection, viral entry is reported to require a low pH in intracytoplasmic vesicles; however, little is known about how SARS-CoV invades such compartments. Here we demonstrate that SARS-CoV mainly utilizes the clathrin-mediated endocytosis pathway for its entry to target cells by using infectious SARS-CoV, as well as a SARS-CoV pseudovirus packaged in the SARS-CoV envelope. The SARS-CoV entered caveolin-1-negative HepG2 cells, and the entry was significantly inhibited by treatment with chlorpromazine, an inhibitor for clathrin-dependent endocytosis, and by small interfering RNA-mediated gene silencing for the clathrin heavy chain. Furthermore, the SARS-CoV entered COS7 cells transfected with the mutant of ACE2 with the cytoplasmic tail deleted, SARS-CoV receptor, as well as the wild-type ACE2, and their entries were significantly inhibited by treatment with chlorpromazine. In addition, ACE2 translocated into EEA1-positive early endosomes immediately after the virus attachment to ACE2. These results suggest that when SARS-CoV binds ACE2 it is internalized and penetrates early endosomes in a clathrin-dependent manner and that the cytoplasmic tail of ACE2 is not required for the penetration of SARS-CoV.",,"['Inoue, Yuuki', 'Tanaka, Nobuyuki', 'Tanaka, Yoshinori', 'Inoue, Shingo', 'Morita, Kouichi', 'Zhuang, Min', 'Hattori, Toshio', 'Sugamura, Kazuo']",,,,
,PMC,"Lambda Interferon (IFN-λ) in Serum Is Decreased in Hantavirus-Infected Patients, and In Vitro-Established Infection Is Insensitive to Treatment with All IFNs and Inhibits IFN-γ-Induced Nitric Oxide Production",http://dx.doi.org/10.1128/JVI.00415-07,PMC1951347,,,"Hantaviruses, causing hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS), are known to be sensitive to nitric oxide (NO) and to pretreatment with type I and II interferons (alpha interferon [IFN-α]/IFN-β and IFN-γ, respectively). Elevated serum levels of NO and IFN-γ have been observed in HFRS patients, but little is known regarding the systemic levels of other IFNs and the possible effects of hantaviruses on innate antiviral immune responses. In Puumala virus-infected HFRS patients (n = 18), we report that the levels of IFN-α and IFN-β are similar, whereas the level of IFN-λ (type III IFN) is significantly decreased, during acute (day of hospitalization) compared to the convalescent phase. The possible antiviral effects of IFN-λ on the prototypic hantavirus Hantaan virus (HTNV) replication was then investigated. Pretreatment of A549 cells with IFN-λ alone inhibited HTNV replication, and IFN-λ combined with IFN-γ induced additive antiviral effects. We then studied the effect of postinfection treatment with IFNs. Interestingly, an already-established HTNV infection was insensitive to subsequent IFN-α, -β, -γ, and -λ stimulation, and HTNV-infected cells produced less NO compared to noninfected cells when stimulated with IFN-γ and IL-1β. Furthermore, less phosphorylated STAT1 after IFN treatment was observed in the nuclei of infected cells than in those of noninfected cells. The results suggest that hantavirus can interfere with the activation of antiviral innate immune responses in patients and inhibit the antiviral effects of all IFNs. We believe that future studies addressing the mechanisms by which hantaviruses interfere with the activation and shaping of immune responses may bring more knowledge regarding HFRS and HCPS pathogenesis.",,"['Stoltz, Malin', 'Ahlm, Clas', 'Lundkvist, Åke', 'Klingström, Jonas']",,,,
,PMC,Adaptation of Borna Disease Virus to New Host Species Attributed to Altered Regulation of Viral Polymerase Activity,http://dx.doi.org/10.1128/JVI.00334-07,PMC1951315,,,"Borna disease virus (BDV) can persistently infect the central nervous system of a broad range of mammalian species. Mice are resistant to infections with primary BDV isolates, but certain laboratory strains can be adapted to replicate in mice. We determined the molecular basis of adaptation by studying mutations acquired by a cDNA-derived BDV strain during one brain passage in rats and three passages in mice. The adapted virus propagated efficiently in mouse brains and induced neurological disease. Its genome contained seven point mutations, three of which caused amino acid changes in the L polymerase (L1116R and N1398D) and in the polymerase cofactor P (R66K). Recombinant BDV carrying these mutations either alone or in combination all showed enhanced multiplication speed in Vero cells, indicating improved intrinsic viral polymerase activity rather than adaptation to a mouse-specific factor. Mutations R66K and L1116R, but not N1398D, conferred replication competence of recombinant BDV in mice if introduced individually. Virus propagation in mouse brains was substantially enhanced if both L mutations were present simultaneously, but infection remained mostly nonsymptomatic. Only if all three amino acid substitutions were combined did BDV replicate vigorously and induce early disease in mice. Interestingly, the virulence-enhancing effect of the R66K mutation in P could be attributed to reduced negative regulation of polymerase activity by the viral X protein. Our data demonstrate that BDV replication competence in mice is mediated by the polymerase complex rather than the viral envelope and suggest that altered regulation of viral gene expression can favor adaptation to new host species.",,"['Ackermann, Andreas', 'Staeheli, Peter', 'Schneider, Urs']",,,,
,PMC,Matrix Fibronectin Binds Gammaretrovirus and Assists in Entry: New Light on Viral Infections,http://dx.doi.org/10.1128/JVI.00312-07,PMC1951278,,,"A major entry route for the gammaretrovirus amphotropic murine leukemia virus (A-MLV) into NIH 3T3 fibroblasts is via caveola-dependent endocytosis. However, during the infection time, few viral particles can be observed intracellularly. Analyzing the dynamics of the A-MLV infection process by using total internal reflection fluorescence microscopy, we show that the majority of viruses are extracellular and bound to the fibronectin matrix. Moreover, the amounts of bound virus and of fibronectin correlated. Using confocal microscopy, nanoparticles targeted to fibronectin by a III1C-fibronectin fragment or anti-fibronectin antibody were detected intracellularly in NIH 3T3 cells; unconjugated nanoparticles neither bound to cells nor were detectable intracellularly. Furthermore, A-MLV colocalized intracellularly with the fibronectin-targeted nanoparticles, suggesting that they were taken up by the same cellular pathway. Both A-MLV entry and fibronectin turnover depend on caveolar endocytosis, and we found that inhibiting viral binding to the extracellular NIH 3T3 fibronectin-matrix dramatically reduced A-MLV infection, indeed, showing an active role of fibronectin in infection. We suggest that binding to the cellular fibronectin matrix provides a new mechanism by which viruses can enter cells.",,"['Beer, Christiane', 'Pedersen, Lene']",,,,
,PMC,Vesicular stomatitis virus vectors expressing avian influenza H5 HA induce cross-neutralizing antibodies and long-term protection,http://dx.doi.org/10.1016/j.virol.2007.04.021,PMC3356997,,,"Given the lethality of H5N1 avian influenza viruses (AIV) and the recurring spread from poultry to humans, an effective vaccine against H5N1 viruses may be needed to prevent a pandemic. We generated experimental vaccine vectors based on recombinant vesicular stomatitis virus (VSV) expressing the H5 hemagglutinin from an H5N1 virus isolated in 1997. The HA gene was expressed either from an attenuated wild-type VSV vector or from a single-cycle vector containing a deletion of the VSV G gene. We found that all of the vectors induced potent neutralizing antibody titers against the homologous and antigenically heterologous H5N1 viruses isolated in 2004 and 2005. Vaccination of mice with any combination of prime or prime/boost vectors provided long-lasting protection (> 7 months) against challenge with AIV, even in animals receiving a single dose of single-cycle vaccine. Our data indicate that these recombinants are promising vaccine candidates for pandemic influenza.",,"['Schwartz, Jennifer A.', 'Buonocore, Linda', 'Roberts, Anjeanette', 'Suguitan, Amorsolo', 'Kobasa, Darwyn', 'Kobinger, Gary', 'Feldmann, Heinz', 'Subbarao, Kanta', 'Rose, John K.']",,,,
,PMC,Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated with viral infectivity,http://dx.doi.org/10.1016/j.bbrc.2007.05.092,PMC2323977,,,"The spike (S) protein of SARS coronavirus (SARS-CoV) has been known to recognize and bind to host receptors, whose conformational changes then facilitates fusion between the viral envelope and host cell membrane, leading to viral entry into target cells. However, other functions of SARS-CoV S protein such as proteolytic cleavage and its implications to viral infection are incompletely understood. In this study, we demonstrated that the infection of SARS-CoV and a pseudovirus bearing the S protein of SARS-CoV was inhibited by a protease inhibitor Ben-HCl. Also, the protease Factor Xa, a target of Ben-HCl abundantly expressed in infected cells, was able to cleave the recombinant and pseudoviral S protein into S1 and S2 subunits, and the cleavage was inhibited by Ben-HCl. Furthermore, this cleavage correlated with the infectivity of the pseudovirus. Taken together, our study suggests a plausible mechanism by which SARS-CoV cleaves its S protein to facilitate viral infection.",,"['Du, Lanying', 'Kao, Richard Y.', 'Zhou, Yusen', 'He, Yuxian', 'Zhao, Guangyu', 'Wong, Charlotte', 'Jiang, Shibo', 'Yuen, Kwok-Yung', 'Jin, Dong-Yan', 'Zheng, Bo-Jian']",,,,
,PMC,Simultaneous Detection and High-Throughput Identification of a Panel of RNA Viruses Causing Respiratory Tract Infections,http://dx.doi.org/10.1128/JCM.00210-07,PMC1932978,,,"Clinical presentations for viral respiratory tract infections are often nonspecific, and a rapid, high-throughput laboratory technique that can detect a panel of common viral pathogens is clinically desirable. We evaluated two multiplex reverse transcription-PCR (RT-PCR) products coupled with microarray-based systems for simultaneous detection of common respiratory tract viral pathogens. The NGEN respiratory virus analyte-specific assay (Nanogen, San Diego, CA) detects influenza A virus (Flu-A) and Flu-B, parainfluenza virus 1 (PIV-1), PIV-2, and PIV-3, and respiratory syncytial virus (RSV), while the ResPlex II assay (Genaco Biomedical Products, Inc., Huntsville, AL) detects Flu-A, Flu-B, PIV-1, PIV-2, PIV-3, PIV-4, RSV, human metapneumovirus (hMPV), rhinoviruses (RhVs), enteroviruses (EnVs), and severe acute respiratory syndrome (SARS) coronavirus (CoV). A total of 360 frozen respiratory specimens collected for a full year were tested, and results were compared to those obtained with a combined reference standard of cell culture and monoplex real-time TaqMan RT-PCR assays. NGEN and ResPlex II gave comparable sensitivities for Flu-A (82.8 to 86.2%), Flu-B (90.0 to 100.0%), PIV-1 (87.5 to 93.8%), PIV-3 (66.7 to 72.2%), and RSV (63.3 to 73.3%); both assays achieved excellent specificities (99.1 to 100.0%) for these five common viruses. The ResPlex II assay detected hMPV in 13 (3.6%) specimens, with a sensitivity of 80.0% and specificity of 99.7%. The ResPlex II assay also differentiated RSV-A and RSV-B and gave positive results for RhV and EnV in 31 (8.6%) and 19 (5.3%) specimens, respectively. PIV-2, PIV-4, and SARS CoV were not detected in the specimens tested. The two systems can process 80 (NGEN) and 96 (ResPlex II) tests per run, with a hands-on time of approximately 60 min and test turnaround times of 6 h (ResPlex II) and 9 h (NGEN). Multiple-panel testing detected an additional unsuspected 9 (3.4%) PIV-1 and 10 (3.7%) PIV-3 infections. While test sensitivities for RSV and PIV-3 need improvement, both the NGEN and ResPlex II assays provide user-friendly and high-throughput tools for simultaneous detection and identification of a panel of common respiratory viral pathogens in a single test format. The multiplex approach enhances diagnosis through detection of respiratory viral etiologic agents in cases in which the presence of the agent was not suspected and a test was not ordered by the clinicians.",,"['Li, Haijing', 'McCormac, Melinda A.', 'Estes, R. Wray', 'Sefers, Susan E.', 'Dare, Ryan K.', 'Chappell, James D.', 'Erdman, Dean D.', 'Wright, Peter F.', 'Tang, Yi-Wei']",,,,
,PMC,GxxxG Motif of Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Transmembrane Domain Is Not Involved in Trimerization and Is Not Important for Entry,http://dx.doi.org/10.1128/JVI.00014-07,PMC1951296,,,"Recently, a paper was published in which it was proposed that the GxxxG motif of the severe acute respiratory syndrome (SARS) coronavirus spike (S) protein transmembrane domain plays a vital role in oligomerization of the protein (E. Arbely, Z. Granot, I. Kass, J. Orly, and I. T. Arkin, Biochemistry 45:11349-11356, 2006). Here, we show that the GxxxG motif is not involved in SARS S oligomerization by trimerization analysis of S GxxxG mutant proteins. In addition, the capability of S to mediate entry of SARS S-pseudotyped particles overall was affected moderately in the mutant proteins, also arguing for a nonvital role for the GxxxG motif in SARS coronavirus entry.",,"['Corver, Jeroen', 'Broer, Rene', 'van Kasteren, Puck', 'Spaan, Willy']",,,,
,PMC,Lipid Rafts of Primary Endothelial Cells Are Essential for Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8-Induced Phosphatidylinositol 3-Kinase and RhoA-GTPases Critical for Microtubule Dynamics and Nuclear Delivery of Viral DNA but Dispensable for Binding and Entry,http://dx.doi.org/10.1128/JVI.02848-06,PMC1951274,,,"Early during de novo infection of human microvascular dermal endothelial (HMVEC-d) cells, Kaposi's sarcoma-associated herpesvirus (KSHV) (human herpesvirus 8 [HHV-8]) induces the host cell's preexisting FAK, Src, phosphatidylinositol 3-kinase (PI3-K), Rho-GTPases, Diaphanous-2 (Dia-2), Ezrin, protein kinase C-ζ, extracellular signal-regulated kinase 1/2 (ERK1/2), and NF-κB signal pathways that are critical for virus entry, nuclear delivery of viral DNA, and initiation of viral gene expression. Since several of these signal molecules are known to be associated with lipid raft (LR) domains, we investigated the role of LR during KSHV infection of HMVEC-d cells. Pretreatment of cells with LR-disrupting agents methyl β-cyclo dextrin (MβCD) or nystatin significantly inhibited the expression of viral latent (ORF73) and lytic (ORF50) genes. LR disruption did not affect KSHV binding but increased viral DNA internalization. In contrast, association of internalized viral capsids with microtubules (MTs) and the quantity of infected nucleus-associated viral DNA were significantly reduced. Disorganized and disrupted MTs and thick rounded plasma membranes were observed in MβCD-treated cells. LR disruption did not affect KSHV-induced FAK and ERK1/2 phosphorylation; in contrast, it increased the phosphorylation of Src, significantly reduced the KSHV-induced PI3-K and RhoA-GTPase and NF-κB activation, and reduced the colocalizations of PI3-K and RhoA-GTPase with LRs. Biochemical characterization demonstrated the association of activated PI3-K with LR fractions which was inhibited by MβCD treatment. RhoA-GTPase activation was inhibited by PI3-K inhibitors, demonstrating that PI3-K is upstream to RhoA-GTPase. In addition, colocalization of Dia-2, a RhoA-GTPase activated molecule involved in MT activation, with LR was reduced. KSHV-RhoA-GTPase mediated acetylation and aggregation of MTs were also reduced. Taken together, these studies suggest that LRs of endothelial cells play critical roles in KSHV infection and gene expression, probably due to their roles in modulating KSHV-induced PI3-K, RhoA-GTPase, and Dia-2 molecules essential for postbinding and entry stages of infection such as modulation of microtubular dynamics, movement of virus in the cytoplasm, and nuclear delivery of viral DNA.",,"['Raghu, Hari', 'Sharma-Walia, Neelam', 'Veettil, Mohanan Valiya', 'Sadagopan, Sathish', 'Caballero, Adriana', 'Sivakumar, Ramu', 'Varga, Laszlo', 'Bottero, Virginie', 'Chandran, Bala']",,,,
,PMC,Synthetic Reconstruction of Zoonotic and Early Human Severe Acute Respiratory Syndrome Coronavirus Isolates That Produce Fatal Disease in Aged Mice,http://dx.doi.org/10.1128/JVI.00505-07,PMC1933338,,,"The severe acute respiratory syndrome (SARS) epidemic was characterized by high mortality rates in the elderly. The molecular mechanisms that govern enhanced susceptibility of elderly populations are not known, and robust animal models are needed that recapitulate the increased pathogenic phenotype noted with increasing age. Using synthetic biology and reverse genetics, we describe the construction of a panel of isogenic SARS coronavirus (SARS-CoV) strains bearing variant spike glycoproteins that are representative of zoonotic strains found in palm civets and raccoon dogs, as well as isolates spanning the early, middle, and late phases of the SARS-CoV epidemic. The recombinant viruses replicated efficiently in cell culture and demonstrated variable sensitivities to neutralization with antibodies. The human but not the zoonotic variants replicated efficiently in human airway epithelial cultures, supporting earlier hypotheses that zoonotic isolates are less pathogenic in humans but can evolve into highly pathogenic strains. All viruses replicated efficiently, but none produced clinical disease or death in young animals. In contrast, severe clinical disease, diffuse alveolar damage, hyaline membrane formation, alveolitis, and death were noted in 12-month-old mice inoculated with the palm civet HC/SZ/61/03 strain or early-human-phase GZ02 variants but not with related middle- and late-phase epidemic or raccoon dog strains. This panel of SARS-CoV recombinants bearing zoonotic and human epidemic spike glycoproteins will provide heterologous challenge models for testing vaccine efficacy against zoonotic reintroductions as well as provide the appropriate model system for elucidating the complex virus-host interactions that contribute to more-severe and fatal SARS-CoV disease and acute respiratory distress in the elderly.",,"['Rockx, Barry', 'Sheahan, Timothy', 'Donaldson, Eric', 'Harkema, Jack', 'Sims, Amy', 'Heise, Mark', 'Pickles, Raymond', 'Cameron, Mark', 'Kelvin, David', 'Baric, Ralph']",,,,
,PMC,Monoclonal antibody-mediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention,http://dx.doi.org/10.1073/pnas.0703498104,PMC1868655,,,"Infection with dengue virus (DENV) or any other flavivirus induces cross-reactive, but weakly neutralizing or nonneutralizing, antibodies that recognize epitopes involving the fusion peptide in the envelope glycoprotein. Humanized mAb IgG 1A5, derived from a chimpanzee, shares properties of cross-reactive antibodies. mAb IgG 1A5 up-regulated DENV infection by a mechanism of antibody-dependent enhancement (ADE) in a variety of Fc receptor-bearing cells in vitro. A 10- to 1,000-fold increase of viral yield in K562 cells, dependent on the DENV serotype, was observed over a range of subneutralizing concentrations of IgG 1A5. A significant increase of DENV-4 viremia titers (up to 100-fold) was also demonstrated in juvenile rhesus monkeys immunized with passively transferred dilutions of IgG 1A5. These results, together with earlier findings of ADE of DENV-2 infection by a polyclonal serum, establish the primate model for analysis of ADE. Considering the abundance of these cross-reactive antibodies, our observations confirm that significant viral amplification could occur during DENV infections in humans with prior infection or with maternally transferred immunity, possibly leading to severe dengue. Strategies to eliminate ADE were explored by altering the antibody Fc structures responsible for binding to Fc receptors. IgG 1A5 variants, containing amino acid substitutions from the Fc region of IgG2 or IgG4 antibodies, reduced but did not eliminate DENV-4-enhancing activity in K562 cells. Importantly, a 9-aa deletion at the N terminus of the CH(2) domain in the Fc region abrogated the enhancing activity.",,"['Goncalvez, Ana P.', 'Engle, Ronald E.', 'St. Claire, Marisa', 'Purcell, Robert H.', 'Lai, Ching-Juh']",,,,
,PMC,Aileen Joy Plant (née Parnell),http://dx.doi.org/10.1136/bmj.39197.625509.BE,PMC1867903,,,An Australian infectious disease epidemiologist widely admired for her global work controlling disease outbreaks and for her capacity for friendship,,"Sweet, Melissa",,,,
,PMC,UK preparedness for pandemic influenza,http://dx.doi.org/10.1136/bmj.39205.591389.80,PMC1867882,,,Devolving responsibility for implementation to local authorities may not be the best policy,,"Coker, Richard",,,,
,PMC,Fluorochrome-linked immunoassay for functional analysis of the mannose binding lectin complement pathway to the level of C3 cleavage,http://dx.doi.org/10.1016/j.jim.2007.04.004,PMC1976379,,,"The humoral response to invading pathogens is mediated by a repertoire of innate immune molecules and receptors able to recognize pathogen-associated molecular patterns. Mannose binding lectin (MBL) and ficolins are initiation molecules of the lectin complement pathway (LCP) that bridge innate and adaptive immunity. Activation of the MBL-dependent lectin pathway, to the level of C3 cleavage, requires functional MASP-2, C2, C4 and C3, all of which have been identified with genetic polymorphisms that can affect protein concentration and function. Current assays for MBL and MASP-2 lack the ability to assess activation of all components to the level of C3 cleavage in a single assay platform. We developed a novel, low volume, fluorochrome linked immunoassay (FLISA) that quantitatively assesses the functional status of MBL, MASP-2 and C3 convertase in a single well. The assay can be used with plasma or serum. Multiple freeze/thaw cycles of serum does not significantly alter the assay, making it ideal for high throughput of large sample databases with minimal volume use. The FLISA can be used potentially to identify specific human disease correlations between these components and clinical outcomes in already established databases.",,"['Walsh, Mary C.', 'Shaffer, Lisa A.', 'Guikema, Benjamin J.', 'Body, Simon C.', 'Shernan, Stanton K.', 'Fox, Amanda A.', 'Collard, Charles D.', 'Fung, Michael', 'Taylor, Ronald P.', 'Stahl, Gregory L.']",,,,
,PMC,Animal Models and Vaccines for SARS-CoV Infection,http://dx.doi.org/10.1016/j.virusres.2007.03.025,PMC2323511,,,"We summarize findings of SARS-CoV infections in several animal models each of which support viral replication in lungs accompanied by histopathological changes and/or clinical signs of illness to varying degrees. New findings are reported on SARS-CoV replication and associated pathology in two additional strains (C57BL/6 and 129S6) of aged mice. We also provide new comparative data on viral replication and associated pathology following infection of golden Syrian hamsters with various SARS-CoV strains and report the levels of neutralizing antibody titers following these infections and the cross-protective efficacy of infection with these strains in protecting against heterologous challenge. Finally, we summarize findings of a variety of vaccine approaches and discuss the available in vitro and in vivo data addressing the potential for disease enhancement following re-infection in animals previously vaccinated against or infected with SARS-CoV.",,"['Roberts, Anjeanette', 'Lamirande, Elaine W.', 'Vogel, Leatrice', 'Jackson, Jadon P.', 'Paddock, Christopher D.', 'Guarner, Jeannette', 'Zaki, Sherif R.', 'Sheahan, Timothy', 'Baric, Ralph', 'Subbarao, Kanta']",,,,
,PMC,Induction of Specific Immune Responses by Severe Acute Respiratory Syndrome Coronavirus Spike DNA Vaccine with or without Interleukin-2 Immunization Using Different Vaccination Routes in Mice,http://dx.doi.org/10.1128/CVI.00019-07,PMC1951058,,,"DNA vaccines induce humoral and cellular immune responses in animal models and humans. To analyze the immunogenicity of the severe acute respiratory syndrome (SARS) coronavirus (CoV), SARS-CoV, spike DNA vaccine and the immunoregulatory activity of interleukin-2 (IL-2), DNA vaccine plasmids pcDNA-S and pcDNA-IL-2 were constructed and inoculated into BALB/c mice with or without pcDNA-IL-2 by using three different immunization routes (the intramuscular route, electroporation, or the oral route with live attenuated Salmonella enterica serovar Typhimurium). The cellular and humoral immune responses were assessed by enzyme-linked immunosorbent assays, lymphocyte proliferation assays, enzyme-linked immunospot assays, and fluorescence-activated cell sorter analyses. The results showed that specific humoral and cellular immunities could be induced in mice by inoculating them with SARS-CoV spike DNA vaccine alone or by coinoculation with IL-2-expressing plasmids. In addition, the immune response levels in the coinoculation groups were significantly higher than those in groups receiving the spike DNA vaccine alone. The comparison between the three vaccination routes indicated that oral vaccination evoked a vigorous T-cell response and a weak response predominantly with subclass immunoglobulin G2a (IgG2a) antibody. However, intramuscular immunization evoked a vigorous antibody response and a weak T-cell response, and vaccination by electroporation evoked a vigorous response with a predominant subclass IgG1 antibody response and a moderate T-cell response. Our findings show that the spike DNA vaccine has good immunogenicity and can induce specific humoral and cellular immunities in BALB/c mice, while IL-2 plays an immunoadjuvant role and enhances the humoral and cellular immune responses. Different vaccination routes also evoke distinct immune responses. This study provides basic information for the design of DNA vaccines against SARS-CoV.",,"['Hu, Hui', 'Lu, Xinya', 'Tao, Ling', 'Bai, Bingke', 'Zhang, Zhenfeng', 'Chen, Yao', 'Zheng, Fangliang', 'Chen, Jianjun', 'Chen, Ze', 'Wang, Hanzhong']",,,,
,PMC,Diagnosis of a Critical Respiratory Illness Caused by Human Metapneumovirus by Use of a Pan-Virus Microarray,http://dx.doi.org/10.1128/JCM.00364-07,PMC1933008,,,"A pan-virus DNA microarray (Virochip) was used to detect a human metapneumovirus (hMPV) strain associated with a critical respiratory tract infection in an elderly adult with chronic lymphocytic leukemia. This infection had previously eluded diagnosis despite extensive microbiological testing for possible etiologic agents. The patient's hMPV strain did not grow in viral culture, and only one of five specific reverse transcription-PCR assays for hMPV was positive.",,"['Chiu, Charles Y.', 'Alizadeh, Ash A.', 'Rouskin, Silvi', 'Merker, Jason D.', 'Yeh, Elaine', 'Yagi, Shigeo', 'Schnurr, David', 'Patterson, Bruce K.', 'Ganem, Don', 'DeRisi, Joseph L.']",,,,
,PMC,Poliovirus Induces Bax-Dependent Cell Death Mediated by c-Jun NH(2)-Terminal Kinase,http://dx.doi.org/10.1128/JVI.02690-06,PMC1933371,,,"Poliovirus (PV) is the causal agent of paralytic poliomyelitis, a disease that involves the destruction of motor neurons associated with PV replication. In PV-infected mice, motor neurons die through an apoptotic process. However, mechanisms by which PV induces cell death in neuronal cells remain unclear. Here, we demonstrate that PV infection of neuronal IMR5 cells induces cytochrome c release from mitochondria and loss of mitochondrial transmembrane potential, both of which are evidence of mitochondrial outer membrane permeabilization. PV infection also activates Bax, a proapoptotic member of the Bcl-2 family; this activation involves its conformational change and its redistribution from the cytosol to mitochondria. Neutralization of Bax by vMIA protein expression prevents cytochrome c release, consistent with a contribution of PV-induced Bax activation to mitochondrial outer membrane permeabilization. Interestingly, we also found that c-Jun NH(2)-terminal kinase (JNK) is activated soon after PV infection and that the PV-cell receptor interaction alone is sufficient to induce JNK activation. Moreover, the pharmacological inhibition of JNK by SP600125 inhibits Bax activation and cytochrome c release. This is, to our knowledge, the first demonstration of JNK-mediated Bax-dependent apoptosis in PV-infected cells. Our findings contribute to our understanding of poliomyelitis pathogenesis at the cellular level.",,"['Autret, Arnaud', 'Martin-Latil, Sandra', 'Mousson, Laurence', 'Wirotius, Aurélie', 'Petit, Frédéric', 'Arnoult, Damien', 'Colbère-Garapin, Florence', 'Estaquier, Jérôme', 'Blondel, Bruno']",,,,
,PMC,Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from human plasma,http://dx.doi.org/10.1073/pnas.0703039104,PMC1866310,,,"Neutralizing antibodies directed against hepatitis C virus (HCV) are present in Igs made from anti-HCV-positive plasma. However, these HCV-specific Igs are largely ineffective in vivo. The mechanism for the poor effectiveness is currently unknown. We hypothesize that the presence of nonneutralizing antibodies in HCV-specific Igs interferes with the function of neutralizing antibodies, resulting in the reduction or blockage of their effect. In the present study, we identified at least two epitopes at amino acid residues 412–419 (epitope I) and 434–446 (epitope II), located downstream of the hypervariable region I within the HCV E2 protein. We demonstrated that epitope I, but not epitope II, was implicated in HCV neutralization and that binding of a nonneutralizing antibody to epitope II completely disrupted virus neutralization mediated by antibody binding at epitope I. The dynamic interaction between nonneutralizing and neutralizing antibodies may thus play a key role in determining the outcomes of HCV infection. Further exploration of this interplay should lead to a better understanding of the mechanisms of neutralization and immune escape and may indicate pathways for the manufacture of an effective HCV-specific Ig product for immune prophylaxis of HCV infection.",,"['Zhang, Pei', 'Wu, Charles G.', 'Mihalik, Kathleen', 'Virata-Theimer, Maria Luisa', 'Yu, Mei-ying W.', 'Alter, Harvey J.', 'Feinstone, Stephen M.']",,,,
,PMC,The role of type I interferon production by dendritic cells in host defense,http://dx.doi.org/10.1016/j.biochi.2007.04.018,PMC2752847,,,"Type I interferons (IFN) and dendritic cells (DC) share an overlapping history, with rapidly accumulating evidence for vital roles for both production of type 1 IFN by DC and the interaction of this IFN both with DC and components of the innate and adaptive immune responses. Within the innate immune response, the plasmacytoid DC (pDC) are the “professional” IFN producing cells, expressing specialized toll-like receptors (TLR7 and -9) and high constitutive expression of IRF-7 that allow them to respond to viruses with rapid and extremely robust IFN production; following activation and production of IFN, the pDC subsequently mature into antigen presenting cells that help to shape the adaptive immune response. However, like most cells in the body, the myeloid or conventional DC (mDC or cDC) also produce type I IFNs, albeit typically at a lower level than that observed with pDC, and this IFN is also important in innate and adaptive immunity induced by these classic antigen presenting cells. These two major DC subsets and their IFN products interact both with each other as well as with NK cells, monocytes, T helper cells, T cytotoxic cells, T regulatory cells and B cells to orchestrate the early immune response. This review will discuss some of the converging history of DC and IFN as well as mechanisms for IFN induction in DC and the effects of this IFN on the developing immune response.",,"['Fitzgerald-Bocarsly, P.', 'Feng, D.']",,,,
,PMC,Disparate Effects of Acute and Chronic Infection with SIVmac239 or SHIV-89.6P on Macaque Plasmacytoid Dendritic Cells,http://dx.doi.org/10.1016/j.virol.2007.03.055,PMC2043480,,,"Blood plasmacytoid dendritic cells (pDCs) contribute to both innate and adaptive immune responses by secreting high levels of IFN-α following acute bacterial and viral infections and indirectly by augmenting cell-mediated immunity. Cross-sectional studies have shown that the number of circulating pDCs in HIV patients, compared to that in uninfected individuals, is reduced. However, since the time of infection is usually unknown in HIV-infected patients, pDC-virus interactions that occur immediately after virus exposure are poorly understood. The current study investigated pDC dynamics during acute and chronic infections of macaques with either SIVmac239 or the pathogenic SIV-HIV chimera, SHIV-89.6P, as models for HIV infection. In three rhesus and three pig-tailed macaques infected intravenously with SIVmac239, the percentages of pDCs in blood declined 2- to 6-fold during the first 6 weeks after infection and remained depressed throughout the disease course. Surprisingly, no consistent, comparable decline in peripheral blood pDCs was observed in six macaques infected with SHIV-89.6P. In this latter group, percentages of pDCs did not correlate with CD4(+) T cells, but there was an inverse relationship with viral load. In addition, when compared to naïve controls, the percentages of pDCs were reduced in spleens and peripheral lymph nodes of SIVmac239- but not SHIV-89.6P-infected animals that had progressed to AIDS. Proviral DNA was detected during the acute phase in pDCs isolated from macaques infected with either virus. These results imply that, even though macaque pDCs can be infected by both SIVmac239 and SHIV-89.6P, the subsequent effects on in vivo pathogenesis differ. The underlying mechanism(s) for these differences is unclear, but the selection of SIV or SHIV as a challenge virus might influence the outcome of some studies, such as those evaluating vaccines or the therapeutic efficacy of drugs.",,"['Reeves, R. Keith', 'Fultz, Patricia N.']",,,,
,PMC,In Vitro Resistance Selection and In Vivo Efficacy of Morpholino Oligomers against West Nile Virus,http://dx.doi.org/10.1128/AAC.00069-07,PMC1913242,,,"We characterize in vitro resistance to and demonstrate the in vivo efficacy of two antisense phosphorodiamidate morpholino oligomers (PMOs) against West Nile virus (WNV). Both PMOs were conjugated with an Arg-rich peptide. One peptide-conjugated PMO (PPMO) binds to the 5′ terminus of the viral genome (5′-end PPMO); the other targets an essential 3′ RNA element required for genome cyclization (3′ conserved sequence I [3′ CSI] PPMO). The 3′ CSI PPMO displayed a broad spectrum of antiflavivirus activity, suppressing WNV, Japanese encephalitis virus, and St. Louis encephalitis virus, as demonstrated by reductions in viral titers of 3 to 5 logs in cell cultures, likely due to the absolute conservation of the 3′ CSI PPMO-targeted sequences among these viruses. The selection and sequencing of PPMO-resistant WNV showed that the 5′-end-PPMO-resistant viruses contained two to three mismatches within the PPMO-binding site whereas the 3′ CSI PPMO-resistant viruses accumulated mutations outside the PPMO-targeted region. The mutagenesis of a WNV infectious clone demonstrated that the mismatches within the PPMO-binding site were responsible for the 5′-end PPMO resistance. In contrast, a U insertion or a G deletion located within the 3′-terminal stem-loop of the viral genome was the determinant of the 3′ CSI PPMO resistance. In a mouse model, both the 5′-end and 3′ CSI PPMOs (administered at 100 or 200 μg/day) partially protected mice from WNV disease, with minimal to no PPMO-mediated toxicity. A higher treatment dose (300 μg/day) caused toxicity. Unconjugated PMOs (3 mg/day) showed neither efficacy nor toxicity, suggesting the importance of the peptide conjugate for efficacy. The results suggest that a modification of the peptide conjugate composition to reduce its toxicity yet maintain its ability to effectively deliver PMO into cells may improve PMO-mediated therapy.",,"['Deas, Tia S.', 'Bennett, Corey J.', 'Jones, Susan A.', 'Tilgner, Mark', 'Ren, Ping', 'Behr, Melissa J.', 'Stein, David A.', 'Iversen, Patrick L.', 'Kramer, Laura D.', 'Bernard, Kristen A.', 'Shi, Pei-Yong']",,,,
,PMC,Modulation of Autoimmunity by Treatment of an Infectious Disease,http://dx.doi.org/10.1128/IAI.00423-07,PMC1932944,,,"Chagas’ heart disease (CHD), caused by the parasite Trypanosoma cruzi, is the most common form of myocarditis in Central America and South America. Some humans and experimental animals develop both humoral and cell-mediated cardiac-specific autoimmunity during infection. Benznidazole, a trypanocidal drug, is effective at reducing parasite load and decreasing the severity of myocarditis in acutely infected patients. We hypothesized that the magnitude of autoimmunity that develops following T. cruzi infection is directly proportional to the amount of damage caused by the parasite. To test this hypothesis, we used benznidazole to reduce the number of parasites in an experimental model of CHD and determined whether this treatment altered the autoimmune response. Infection of A/J mice with the Brazil strain of T. cruzi leads to the development of severe inflammation, fibrosis, necrosis, and parasitosis in the heart accompanied by vigorous cardiac myosin-specific delayed-type hypersensitivity (DTH) and antibody production at 21 days postinfection. Mice succumbed to infection within a month if left untreated. Treatment of infected mice with benznidazole eliminated mortality and decreased disease severity. Treatment also reduced cardiac myosin-specific DTH and antibody production. Reinfection of treated mice with a heart-derived, virulent strain of T. cruzi or immunization with myosin led to the redevelopment of myosin-specific autoimmune responses and inflammation. These results provide a direct link between the levels of T. cruzi and the presence of autoimmunity and suggest that elimination of the parasite may result in the reduction or elimination of autoimmunity in the chronic phase of infection.",,"['Hyland, Kenneth V.', 'Leon, Juan S.', 'Daniels, Melvin D.', 'Giafis, Nick', 'Woods, LaKitta M.', 'Bahk, Thomas J.', 'Wang, Kegiang', 'Engman, David M.']",,,,
,PMC,SIMULATION AND VISUALIZATION OF FLOW PATTERN IN MICROARRAYS FOR LIQUID PHASE OLIGONUCLEOTIDE AND PEPTIDE SYNTHESIS,http://dx.doi.org/10.1021/bp060363o,PMC2531222,,,"Microfluidic microarrays have been developed for economical and rapid parallel synthesis of oligonucleotide and peptide libraries. For a synthesis system to be reproducible and uniform, it is crucial to have a uniform reagent delivery throughout the system. Computational fluid dynamics (CFD) is used to model and simulate the microfluidic microarrays to study geometrical effects on flow patterns. By proper design geometry, flow uniformity could be obtained in every microreactor in the microarrays.",,"['O-Charoen, Sirimon', 'Srivannavit, Onnop', 'Gulari, Erdogan']",,,,
,PMC,Modelling respiratory infection control measure effects,http://dx.doi.org/10.1017/S0950268807008631,PMC2870817,,,"One of the most pressing issues in facing emerging and re-emerging respiratory infections is how to bring them under control with current public health measures. Approaches such as the Wells–Riley equation, competing-risks model, and Von Foerster equation are used to prioritize control-measure efforts. Here we formulate how to integrate those three different types of functional relationship to construct easy-to-use and easy-to-interpret critical-control lines that help determine optimally the intervention strategies for containing airborne infections. We show that a combination of assigned effective public health interventions and enhanced engineering control measures would have a high probability for containing airborne infection. We suggest that integrated analysis to enhance modelling the impact of potential control measures against airborne infections presents an opportunity to assess risks and benefits. We demonstrate the approach with examples of optimal control measures to prioritize respiratory infections of severe acute respiratory syndrome (SARS), influenza, measles, and chickenpox.",,"['LIAO, C.\xa0M.', 'CHEN, S.\xa0C.', 'CHANG, C.\xa0F.']",,,,
,PMC,Comparison of Immunoglobulin G Responses to the Spike and Nucleocapsid Proteins of Severe Acute Respiratory Syndrome (SARS) Coronavirus in Patients with SARS,http://dx.doi.org/10.1128/CVI.00432-06,PMC1951070,,,"Both the nucleocapsid (N) and the spike (S) proteins of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) are able to induce strong humoral responses in humans following an infection. To compare the immunoglobulin G (IgG) responses to the S and N proteins of SARS-CoV in SARS patients during the manifestation/convalescent period with those during the postinfection period, serum samples were collected from hospitalized SARS patients within 6 weeks after the onset of illness (set 1; 57 sequential samples from 19 patients) or 2 to 3 months after their recovery (set 2; 33 postinfection samples from 33 subjects). Serum samples from 100 healthy blood donors (set 3), collected in 2002, were also included. The specific IgG response to whole virus, the fragment from positions 450 to 650 of the S protein (S450-650), and the full-length N protein of SARS-CoV were measured by enzyme-linked immunosorbent assays (ELISAs). Western blot assays were carried out to confirm the ELISA results. Fifty-one of the serum samples in set 1 (89%) bound to the N protein, a proportion similar to that which recognized whole virus (79%) and the S-protein fragment (77%). All 33 serum samples from set 2 were strongly positive for N-protein-specific IgG, while 27 (82%) were positive for anti-S450-650 IgG. Two of the serum samples from set 3 were strongly positive for anti-N-protein IgG but not anti-S450-650 IgG. Similar levels of IgG responses to the S and N proteins were observed in SARS patients during the manifestation and convalescent stages. In the postinfection period, however, a number of patients had much lower serum IgG levels against S450-650 than against the N protein.",,"['Zhao, Jincun', 'Wang, Wei', 'Wang, Wenling', 'Zhao, Zhendong', 'Zhang, Yan', 'Lv, Ping', 'Ren, Furong', 'Gao, Xiao-Ming']",,,,
,PMC,Real-Time PCR for Diagnosis of Human Bocavirus Infections and Phylogenetic Analysis,http://dx.doi.org/10.1128/JCM.00027-07,PMC1932993,,,"The human bocavirus (hBoV) was first described in 2005 in respiratory tract samples. The clinical relevance of hBoV is still unclear. The aim of our study was to establish a real-time PCR assay for the detection and quantification of hBoV DNA, to apply the real-time assay for the analysis of stool and serum samples for the presence of hBoV DNA, and to perform a phylogenetic analysis of the hBoV positive samples. A total of 834 nasopharyngeal aspirates (NPA), 10 serum samples, and 31 stool samples of children with acute respiratory diseases were retrospectively tested. For phylogenetic analysis, 968 bp of the VP2 gene were sequenced from 69 hBoV-positive NPA samples. The qualitative results of the real-time hBoV PCR were in good agreement with a conventional hBoV PCR. We found that 12% of the NPA were positive for hBoV DNA. The median viral load in the NPA was 4.9 × 10(3) copies/ml (range, 2.7 × 10° to 1.5 × 10(11) copies/ml). There was no difference of the hBoV load in NPA between children with or without known coinfection, but the load was significantly higher in children with bronchitis than in children with the diagnosis of febrile seizures. hBoV DNA was found in 1 of 10 serum samples and in 14 of 31 stool samples. hBoV sequence identity was >99% in the VP2 region. In conclusion, hBoV DNA can be found in NPA samples at very high titers. In addition to being found in the respiratory tract, hBoV was found in stool samples. The clinical relevance of these findings remains to be determined.",,"['Neske, Florian', 'Blessing, Kerstin', 'Tollmann, Franz', 'Schubert, Jörg', 'Rethwilm, Axel', 'Kreth, Hans Wolfgang', 'Weissbrich, Benedikt']",,,,
,PMC,An RNA Stem-Loop within the Bovine Coronavirus nsp1 Coding Region Is a cis-Acting Element in Defective Interfering RNA Replication,http://dx.doi.org/10.1128/JVI.00549-07,PMC1933353,,,"Higher-order cis-acting RNA replication structures have been identified in the 3′- and 5′-terminal untranslated regions (UTRs) of a bovine coronavirus (BCoV) defective interfering (DI) RNA. The UTRs are identical to those in the viral genome, since the 2.2-kb DI RNA is composed of only the two ends of the genome fused between an internal site within the 738-nucleotide (nt) 5′-most coding region (the nsp1, or p28, coding region) and a site just 4 nt upstream of the 3′-most open reading frame (ORF) (the N gene). The joined ends of the viral genome in the DI RNA create a single continuous 1,635-nt ORF, 288 nt of which come from the 738-nt nsp1 coding region. Here, we have analyzed features of the 5′-terminal 288-nt portion of the nsp1 coding region within the continuous ORF that are required for DI RNA replication. We observed that (i) the 5′-terminal 186 nt of the nsp1 coding region are necessary and sufficient for DI RNA replication, (ii) two Mfold-predicted stem-loops within the 186-nt sequence, named SLV (nt 239 to 310) and SLVI (nt 311 to 340), are supported by RNase structure probing and by nucleotide covariation among closely related group 2 coronaviruses, and (iii) SLVI is a required higher-order structure for DI RNA replication based on mutation analyses. The function of SLV has not been evaluated. We conclude that SLVI within the BCoV nsp1 coding region is a higher-order cis-replication element for DI RNA and postulate that it functions similarly in the viral genome.",,"['Brown, Cary G.', 'Nixon, Kimberley S.', 'Senanayake, Savithra D.', 'Brian, David A.']",,,,
,PMC,Novel Strategy for Treatment of Viral Central Nervous System Infection by Using a Cell-Permeating Inhibitor of c-Jun N-Terminal Kinase,http://dx.doi.org/10.1128/JVI.00467-07,PMC1933289,,,"Viral encephalitis is a major cause of morbidity and mortality worldwide, yet there is no proven efficacious therapy for most viral infections of the central nervous system (CNS). Many of the viruses that cause encephalitis induce apoptosis and activate c-Jun N-terminal kinase (JNK) following infection. We have previously shown that reovirus infection of epithelial cell lines activates JNK-dependent apoptosis. We now show that reovirus infection resulted in activation of JNK and caspase-3 in the CNS. Treatment of reovirus-infected mice with a cell-permeating peptide that competitively inhibits JNK activity resulted in significantly prolonged survival of intracerebrally infected mice following an otherwise lethal challenge with T3D (100× 50% lethal dose). Protection correlated with reduced CNS injury, reduced neuronal apoptosis, and reduced c-Jun activation without altering the viral titer or viral antigen distribution. Given the efficacy of the inhibitor in protecting mice from viral encephalitis, JNK inhibition represents a promising and novel treatment strategy for viral encephalitis.",,"['Beckham, J. David', 'Goody, Robin J.', 'Clarke, Penny', 'Bonny, Christophe', 'Tyler, Kenneth L.']",,,,
,PMC,Emergence of Anti-Red Blood Cell Antibodies Triggers Red Cell Phagocytosis by Activated Macrophages in a Rabbit Model of Epstein-Barr Virus-Associated Hemophagocytic Syndrome,http://dx.doi.org/10.2353/ajpath.2007.060772,PMC1854957,,,"Hemophagocytic syndrome (HPS) is a fatal complication frequently associated with viral infections. In childhood HPS, Epstein-Barr virus (EBV) is the major causative agent, and red blood cells (RBCs) are predominantly phagocytosed by macrophages. To investigate the mechanism of RBC phagocytosis triggered by EBV infection, we adopted a rabbit model of EBV-associated HPS previously established by using Herpesvirus papio (HVP). The kinetics of virus-host interaction was studied. Using flow cytometry, we detected the emergence of antibody-coated RBCs, as well as anti-platelet antibodies, at peak virus load period at weeks 3 to 4 after HVP injection, and the titers increased thereafter. The presence of anti-RBCs preceded RBC phagocytosis in tissues and predicted the full-blown development of HPS. The anti-RBC antibodies showed cross-reactivity with Paul-Bunnell heterophile antibodies. Preabsorption of the HVP-infected serum with control RBCs removed the majority of anti-RBC activities and remarkably reduced RBC phagocytosis. The RBC phagocytosis was specifically mediated via an Fc fragment of antibodies in the presence of macrophage activation. Therefore, the emergence of anti-RBC antibodies and the presence of macrophage activation are both essential in the development of HPS. Our observations in this animal model provide a potential mechanism for hemophagocytosis in EBV infection.",,"['Hsieh, Wen-Chuan', 'Chang, Yao', 'Hsu, Mei-Chi', 'Lan, Bau-Shin', 'Hsiao, Guan-Chung', 'Chuang, Huai-Chia', 'Su, Ih-Jen']",,,,
,PMC,Immunization in Canada 2007,,PMC2533546,,,,,"Embree, Joanne",,,,
,PMC,Was WHO SARS-related Travel Advisory for Toronto Ethical?,http://dx.doi.org/10.1007/BF03403714,PMC6975986,,,"Freedom of movement is undoubtedly a fundamental international right. However, circumstances may arise where that right must be curtailed. Was the 2003 SARS outbreak in Toronto one such circumstance? Guénaël R.M. Rodier thinks WHO’s decision to impose a SARS-related travel advisory was justifiable, even reasonable, though it caused a loss of over $1.1 billion in the Greater Toronto Area. That travel to an infected area was the most common epidemiological link with SARS infections supports Rodier’s position. However, as suggested in the Naylor report, issuing a travel advisory does not keep infected individuals from leaving Toronto and such individuals account for 5 of 6 cases where SARS was spread from Canada. That alone would discount Rodier’s argument and the WHO decision on purely logistical grounds. But there is an ethical question as well. Was the travel advisory implemented fairly? This question is best judged using Nancy E. Kass’s framework for public health. From that framework, two points are placed in immediate relief. First, the Toronto authorities were not given an opportunity to state their case to WHO before the travel advisory was implemented. Second, the framework requires that burdens be distributed fairly and the travel advisory did not do that, or even attempt to do so.",,"Paquin, Leo J.",,,,
,PMC,"Use of an enzyme-linked immunosorbent assay in bulk milk to estimate the prevalence of Neospora caninum on dairy farms in Prince Edward Island, Canada",,PMC1852591,,,"This study evaluated the use of bulk milk as a diagnostic tool for estimation of herd-level Neospora caninum exposure in Atlantic Canada; it was used to estimate the prevalence of dairy farms with a within-herd N. caninum-seroprevalence ≥ 15% in Prince Edward Island (PEI). The variation over time of N. caninum antibodies in bulk milk is also reported. Skimmed bulk milk and individual serum samples were analyzed for N. caninum antibodies by using an enzyme-linked immunosorbent assay (ELISA). Bulk milk samples were collected in May 2004 (n = 235), May 2005 (n = 189), and June 2005 (n = 235). The prevalence of dairy farms with a within-herd seroprevalence ≥ 15% on PEI was 6.4% in May 2004. In May and June 2005, respectively, 10.1% and 10.2% of farms had a ≥ 15% within-herd seroprevalence. In 11 farms that were considered positive based on bulk milk samples, blood samples were collected from all adult cows in September 2005, in conjunction with a 4th bulk milk sample on the same day. The correlation coefficient between serology and bulk milk ELISA was 0.87. The results of this study demonstrate that the prevalence of N. caninum in dairy farms can be estimated by using a bulk milk ELISA.",,"['Wapenaar, Wendela', 'Barkema, Herman W.', 'O’Handley, Ryan M.', 'Bartels, Chris J.M.']",,,,
,PMC,Myelin Transcription Factor 1 (Myt1) Expression in Demyelinated Lesions of Rodent and Human CNS,http://dx.doi.org/10.1002/glia.20492,PMC2789289,,,"Myelin transcription factor 1 (Myt1) is a zinc-finger DNA binding protein that influences developing oligodendrocyte progenitor (OP) cell proliferation, differentiation, and myelin gene transcription in vitro. The potential of Myt1 to play a role in OP responses leading to remyelination was examined using murine hepatitis virus strain A59 (MHV) to induce spinal cord demyelination and potential relevance to human pathology was evaluated in multiple sclerosis (MS) lesions. In MHV-infected mice, the density of Myt1 expressing cells markedly increased in lesioned areas of spinal cord white matter. Myt1 expressing cells proliferated most extensively during active demyelination and subsequently accumulated to maximal levels during early remyelination. Cells with nuclear Myt1 immunoreactivity were mainly OP cells, identified by co-localization with platelet-derived growth factor alpha receptor, with additional phenotypes being either oligodendrocytes or neural stem cells, identified by CC1 antigen and Musashi1, respectively. The density of OP cells expressing Myt1 was significantly increased in white matter of MHV-infected mice during demyelination and early remyelination then as remyelination advanced the values returned to levels comparable to PBS-injected control mice. In MHV lesions, Myt1 was not expressed in astrocytes, lymphocytes, or macrophage/micro-glial cells. MS lesions demonstrated increased Myt1 expression in both the periplaque white matter adjacent to lesions and within early remyelinating lesions. These results suggest a potential role for Myt1 in the regeneration of oligodendrocyte lineage cells in response to demyelination.",,"['Vana, Adam C.', 'Lucchinetti, Claudia F.', 'Le, Tuan Q.', 'Armstrong, Regina C.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00561-07,PMC1900220,,,,,,,,,
,PMC,A U-turn motif-containing stem–loop in the coronavirus 5′ untranslated region plays a functional role in replication,http://dx.doi.org/10.1261/rna.261807,PMC1852815,,,"The 5′ untranslated region (UTR) of the mouse hepatitis virus (MHV) genome contains cis-acting sequences necessary for transcription and replication. A consensus secondary structural model of the 5′ 140 nucleotides of the 5′ UTRs of nine coronaviruses (CoVs) derived from all three major CoV groups is presented and characterized by three major stem–loops, SL1, SL2, and SL4. NMR spectroscopy provides structural support for SL1 and SL2 in three group 2 CoVs, including MHV, BCoV, and HCoV-OC43. SL2 is conserved in all CoVs, typically containing a pentaloop (C47-U48-U49-G50-U51 in MHV) stacked on a 5 base-pair stem, with some sequences containing an additional U 3′ to U51; SL2 therefore possesses sequence features consistent with a U-turn-like conformation. The imino protons of U48 in the wild-type RNA, and G48 in the U48G SL2 mutant RNA, are significantly protected from exchange with solvent, consistent with a hydrogen bonding interaction critical to the hairpin loop architecture. SL2 is required for MHV replication; MHV genomes containing point substitutions predicted to perturb the SL2 structure (U48C, U48A) were not viable, while those that maintain the structure (U48G and U49A) were viable. The U48C MHV mutant supports both positive- and negative-sense genome-sized RNA synthesis, but fails to direct the synthesis of positive- or negative-sense subgenomic RNAs. These data support the existence of the SL2 in our models, and further suggest a critical role in coronavirus replication.",,"['Liu, Pinghua', 'Li, Lichun', 'Millership, Jason J.', 'Kang, Hyojeung', 'Leibowitz, Julian L.', 'Giedroc, David P.']",,,,
,PMC,Seco-pregnane steroids target the subgenomic RNA of alphavirus-like RNA viruses,http://dx.doi.org/10.1073/pnas.0702398104,PMC1876575,,,"Plants have evolved multiple mechanisms to selectively suppress pathogens by production of secondary metabolites with antimicrobial activities. Therefore, direct selections for antiviral compounds from plants can be used to identify new agents with potent antiviral activity but not toxic to hosts. Here, we provide evidence that a class of compounds, seco-pregnane steroid glaucogenin C and its monosugar-glycoside cynatratoside A of Strobilanthes cusia and three new pantasugar-glycosides of glaucogenin C of Cynanchum paniculatum, are effective and selective inhibitors to alphavirus-like positive-strand RNA viruses including plant-infecting tobacco mosaic virus (TMV) and animal-infecting Sindbis virus (SINV), eastern equine encephalitis virus, and Getah virus, but not to other RNA or DNA viruses, yet they were not toxic to host cells. In vivo administration of the compounds protected BALB/c mice from lethal SINV infection without adverse effects on the mice. Using TMV and SINV as models, studies on the action mechanism revealed that the compounds predominantly suppress the expression of viral subgenomic RNA(s) without affecting the accumulation of viral genomic RNA. Our work suggested that the viral subgenomic RNA could be a new target for the discovery of antiviral drugs, and that seco-pregnane steroid and its four glycosides found in the two medicinal herbs have the potential for further development as antiviral agents against alphavirus-like positive-strand RNA viruses.",,"['Li, Yanmei', 'Wang, Lihua', 'Li, Shunlin', 'Chen, Xiaoying', 'Shen, Yuemao', 'Zhang, Zhongkai', 'He, Hongping', 'Xu, Wenbo', 'Shu, Yuelong', 'Liang, Guodong', 'Fang, Rongxiang', 'Hao, Xiaojiang']",,,,
,PMC,SARS-CoV: Lessons for global health,http://dx.doi.org/10.1016/j.virusres.2007.03.024,PMC2633111,,,,,"Baric, Ralph Steven",,,,
,PMC,Biochemical mechanism of hepatitis C virus inhibition by the broad-spectrum antiviral arbidol,http://dx.doi.org/10.1021/bi700181j,PMC2532706,,,"Hepatitis C affects about 3% of the world population, yet its current treatment options are limited to interferon-ribavirin drug regimens which achieve a 50-70% cure rate depending on the hepatitis C virus (HCV) genotype. Besides extensive screening for HCV-specific compounds, some well-established medicinal drugs have recently demonstrated anti-HCV effect in HCV replicon cells. One of these drugs is arbidol (ARB), a Russian-made broad spectrum antiviral agent, which we have previously shown to inhibit acute and chronic HCV infection. Here we show that ARB inhibits the cell entry of HCV pseudoparticles of genotypes 1a, 1b and 2a in a dose-dependent fashion. ARB also displayed a dose-dependent inhibition of HCV membrane fusion, as assayed by using HCV pseudoparticles (HCVpp) and fluorescent liposomes. ARB inhibition of HCVpp fusion was found more effective on genotype 1a than on genotypes 1b and 2a. In vitro biochemical studies revealed ARB association with membrane-like environments such as detergents, and with lipid membranes. This association was particularly prominent at acidic pH which is optimal for HCV-mediated fusion. Our results suggest that the affinity of ARB for lipid membranes could account for its anti-HCV actions, together with a differential level of interaction with key motifs in HCV glycoproteins of different genotypes.",,"['Pécheur, Eve-Isabelle', 'Lavillette, Dimitri', 'Alcaras, Fanny', 'Molle, Jennifer', 'Boriskin, Yury S.', 'Roberts, Michael', 'Cosset, François-Loïc', 'Polyak, Stephen J.']",,,,
,PMC,"Seroprevalence of Selected Infectious Agents in a Free-Ranging, Low-Density Lion Population in the Central Kalahari Game Reserves in Botswana",http://dx.doi.org/10.1128/CVI.00307-06,PMC1951071,,,"Twenty-one free-ranging Central Kalahari lions (Panthera leo) exhibited a high prevalence rate of feline herpesvirus (100%) and feline immunodeficiency virus (71.4%). Canine distemper virus and feline calicivirus occurred with a low prevalence. All individuals tested negative for feline coronavirus, feline parvovirus, feline leukemia virus, Ehrlichia canis, and Anaplasma phagocytophilum.",,"['Ramsauer, Sandra', 'Bay, Gert', 'Meli, Marina', 'Hofmann-Lehmann, Regina', 'Lutz, Hans']",,,,
,PMC,"Outbreak of Human Metapneumovirus Detected by Use of the Vero E6 Cell Line in Isolates Collected in Yamagata, Japan, in 2004 and 2005",http://dx.doi.org/10.1128/JCM.01251-06,PMC1933089,,,"A number of epidemiological studies have shown human metapneumovirus (hMPV) to be one of the most important viral agents associated with acute respiratory infections in humans. However, due to the difficulty in growing the virus, all epidemiological studies of hMPV infection have been performed on the basis of the molecular method. Thus, the development of a cell line suitable for the isolation of hMPV from clinical specimens is a crucial step for further research. Using the Vero E6 cell line, which could be stably maintained for 1 month without passage or medium change, we succeeded in isolating 79 strains from 4,112 specimens obtained in Yamagata, Japan, in 2004 and 2005. The total isolation rate was 1.9% (79/4,112). The monthly distribution revealed that hMPV infections occurred between February and April in 2004 and throughout most of the year in 2005. Phylogenetic analysis indicated that subgenogroup B2 was predominant in 2004, whereas three subgenogroups, A2, B1, and B2, had cocirculated in 2005. Although multiple subgenogroups cocirculated in 2005, each individual subgenogroup strain was found to predominate at specific sites. An infectivity assay of hMPV strains also indicated that the infection efficiency in Vero E6 cells was better than that in LLC-MK2 cells. Finally, we found that Vero E6 cells are useful for the isolation of hMPVs and that this utility might aid further research into hMPVs beyond the epidemiological data shown in this study.",,"['Abiko, C.', 'Mizuta, K.', 'Itagaki, T.', 'Katsushima, N.', 'Ito, S.', 'Matsuzaki, Y.', 'Okamoto, M.', 'Nishimura, H.', 'Aoki, Y.', 'Murata, T.', 'Hoshina, H.', 'Hongo, S.', 'Ootani, K.']",,,,
,PMC,A Cluster of Legionella-Associated Pneumonia Cases in a Population of Military Recruits,http://dx.doi.org/10.1128/JCM.02359-06,PMC1933087,,,"A Legionella cluster was identified through retrospective PCR analysis of 240 throat swab samples from X-ray-confirmed pneumonia cases. These were identified among young and otherwise healthy U.S. military recruits during population-based surveillance for pneumonia pathogens. Results were confirmed by sequence analysis. Cases clustered tightly, suggesting a local environmental etiology.",,"['McDonough, Erin A.', 'Metzgar, David', 'Hansen, Christian J.', 'Myers, Christopher A.', 'Russell, Kevin L.']",,,,
,PMC,DNA Immunization with Plasmids Encoding Fusion and Nucleocapsid Proteins of Bovine Respiratory Syncytial Virus Induces a Strong Cell-Mediated Immunity and Protects Calves against Challenge,http://dx.doi.org/10.1128/JVI.00502-07,PMC1933320,,,"Respiratory syncytial viruses (RSV) are one of the most important respiratory pathogens of humans and cattle, and there is currently no safe and effective vaccine prophylaxis. In this study, we designed two codon-optimized plasmids encoding the bovine RSV fusion (F) and nucleocapsid (N) proteins and assessed their immunogenicity in young calves. Two administrations of both plasmids elicited low antibody levels but primed a strong cell-mediated immunity characterized by lymphoproliferative response and gamma interferon production in vitro and in vivo. Interestingly, this strong cellular response drastically reduced viral replication, clinical signs, and pulmonary lesions after a highly virulent challenge. Moreover, calves that were further vaccinated with a killed-virus vaccine developed high levels of neutralizing antibody and were fully protected following challenge. These results indicate that DNA vaccination could be a promising alternative to the classical vaccines against RSV in cattle and could therefore open perspectives for vaccinating young infants.",,"['Boxus, Mathieu', 'Tignon, Marylène', 'Roels, Stefan', 'Toussaint, Jean-François', 'Walravens, Karl', 'Benoit, Marie-Ange', 'Coppe, Philippe', 'Letesson, Jean-Jacques', 'Letellier, Carine', 'Kerkhofs, Pierre']",,,,
,PMC,Detection of a Novel and Highly Divergent Coronavirus from Asian Leopard Cats and Chinese Ferret Badgers in Southern China,http://dx.doi.org/10.1128/JVI.00299-07,PMC1933311,,,"Since an outbreak of severe acute respiratory syndrome (SARS) was averted in 2004, many novel coronaviruses have been recognized from different species, including humans. Bats have provided the most diverse assemblages of coronaviruses, suggesting that they may be the natural reservoir. Continued virological surveillance has proven to be the best way to avert this infectious disease at the source. Here we provide the first description of a previously unidentified coronavirus lineage detected from wild Asian leopard cats (Prionailurus bengalensis) and Chinese ferret badgers (Melogale moschata) during virological surveillance in southern China. Partial genome analysis revealed a typical coronavirus genome but with a unique putative accessory gene organization. Phylogenetic analyses revealed that the envelope, membrane, and nucleoprotein structural proteins and the two conserved replicase domains, putative RNA-dependent RNA polymerase and RNA helicase, of these novel coronaviruses were most closely related to those of group 3 coronaviruses identified from birds, while the spike protein gene was most closely related to that of group 1 coronaviruses from mammals. However, these viruses always fell into an outgroup phylogenetic relationship with respect to other coronaviruses and had low amino acid similarity to all known coronavirus groups, indicating that they diverged early in the evolutionary history of coronaviruses. These results suggest that these viruses may represent a previously unrecognized evolutionary pathway, or possibly an unidentified coronavirus group. This study demonstrates the importance of systematic virological surveillance in market animals for understanding the evolution and emergence of viruses with infectious potential.",,"['Dong, B. Q.', 'Liu, W.', 'Fan, X. H.', 'Vijaykrishna, D.', 'Tang, X. C.', 'Gao, F.', 'Li, L. F.', 'Li, G. J.', 'Zhang, J. X.', 'Yang, L. Q.', 'Poon, L. L. M.', 'Zhang, S. Y.', 'Peiris, J. S. M.', 'Smith, G. J. D.', 'Chen, H.', 'Guan, Y.']",,,,
,PMC,Enhanced Antiviral Activity against Foot-and-Mouth Disease Virus by a Combination of Type I and II Porcine Interferons,http://dx.doi.org/10.1128/JVI.02775-06,PMC1933294,,,"Previously, we showed that type I interferon (alpha/beta interferon [IFN-α/β]) can inhibit foot-and-mouth disease virus (FMDV) replication in cell culture, and swine inoculated with 10(9) PFU of human adenovirus type 5 expressing porcine IFN-α (Ad5-pIFN-α) were protected when challenged 1 day later. In this study, we found that type II pIFN (pIFN-γ) also has antiviral activity against FMDV in cell culture and that, in combination with pIFN-α, it has a synergistic antiviral effect. We also observed that while each IFN alone induced a number of IFN-stimulated genes (ISGs), the combination resulted in a synergistic induction of some ISGs. To extend these studies to susceptible animals, we inoculated groups of swine with a control Ad5, 10(8) PFU of Ad5-pIFN-α, low- or high-dose Ad5-pIFN-γ, or a combination of Ad5-pIFN-α and low- or high-dose Ad5-pIFN-γ and challenged all groups with FMDV 1 day later. The control group and the groups inoculated with either Ad5-pIFN-α or a low dose of Ad5-pIFN-γ developed clinical disease and viremia. However, the group that received the combination of both Ad5-IFNs with the low dose of Ad5-pIFN-γ was completely protected from challenge and had no viremia. Similarly the groups inoculated with the combination of Ad5s with the higher dose of Ad5-pIFN-γ or with only high-dose Ad5-pIFN-γ were protected. The protected animals did not develop antibodies against viral nonstructural (NS) proteins, while all infected animals were NS protein seropositive. No antiviral activity or significant levels of IFNs were detected in the protected groups, but there was an induction of some ISGs. The results indicate that the combination of type I and II IFNs act synergistically to inhibit FMDV replication in vitro and in vivo.",,"['Moraes, Mauro Pires', 'de los Santos, Teresa', 'Koster, Marla', 'Turecek, Traci', 'Wang, He', 'Andreyev, Vladimir G.', 'Grubman, Marvin J.']",,,,
,PMC,Inhibition of the Alpha/Beta Interferon Response by Mouse Hepatitis Virus at Multiple Levels,http://dx.doi.org/10.1128/JVI.00013-07,PMC1933268,,,"Mouse hepatitis virus (MHV) was used as a model to study the interaction of coronaviruses with the alpha/beta interferon (IFN-α/β) response. While MHV strain A59 appeared to induce IFN-β gene transcription and low levels of nuclear translocation of the IFN-β transcription factor interferon regulatory factor 3 (IRF-3), MHV did not induce IFN-β protein production during the course of infection in L2 mouse fibroblast cells. In addition, MHV was able to significantly decrease the level of IFN-β protein induced by both Newcastle disease virus (NDV) and Sendai virus infections, without targeting it for proteasomal degradation and without altering the nuclear translocation of IRF-3 or IFN-β mRNA production or stability. These results indicate that MHV infection causes an inhibition of IFN-β production at a posttranscriptional level, without altering RNA or protein stability. In contrast, MHV induced IFN-β mRNA and protein production in the brains of infected animals, suggesting that the inhibitory mechanisms observed in vitro are not enough to prevent IFN-α/β production in vivo. Furthermore, MHV replication is highly resistant to IFN-α/β action, as indicated by unimpaired MHV replication in L2 cells pretreated with IFN-β. However, when L2 cells were coinfected with MHV and NDV in the presence of IFN-β, NDV, but not MHV, replication was inhibited. Thus, rather than disarming the antiviral activity induced by IFN-β pretreatment completely, MHV may be inherently resistant to some aspects of the antiviral state induced by IFN-β. These findings show that MHV employs unique strategies to circumvent the IFN-α/β response at multiple steps.",,"['Roth-Cross, Jessica K.', 'Martínez-Sobrido, Luis', 'Scott, Erin P.', 'García-Sastre, Adolfo', 'Weiss, Susan R.']",,,,
,PMC,Pandemic influenza: Studying the lessons of history,http://dx.doi.org/10.1073/pnas.0702659104,PMC1863464,,,,,"Morse, Stephen S.",,,,
,PMC,Production of High-Affinity Human Monoclonal Antibody Fab Fragments to the 19-Kilodalton C-Terminal Merozoite Surface Protein 1 of Plasmodium falciparum,http://dx.doi.org/10.1128/IAI.00062-07,PMC1932930,,,"A combinatorial immunoglobulin gene library was constructed from peripheral blood lymphocytes of eight patients infected with Plasmodium falciparum and was screened for the production of human monoclonal antibody Fab fragments to the C-terminal 19-kDa fragment of P. falciparum merozoite surface protein 1 (MSP-1(19)). Three Fab clones recognized recombinant MSP-1(19) under nonreducing conditions. Indirect immunofluorescence microscopy demonstrated that three Fab clones stained the surfaces of late trophozoites/schizonts and merozoites of the FCR3 and 3D7 strains, suggesting the Fabs' reactivities to a conserved epitope. Sequence analysis of the heavy-chain genes revealed that the closest germ line V segments were VH1-8 and VH7-81, with 91% to 98% homology. The closest germ line D segment was D3-10, and the closest germ line J segment was JH4 or JH5, with 90% to 97% homology. In the light-chain genes, the closest germ line V segment was A27 for the Jκ2, Jκ4, and Jκ5 segments. The dissociation constants of these Fab fragments for recombinant MSP-1(19) ranged from 1.09 × 10(−9) to 2.66 × 10(−9) M. The binding of the three Fab fragments to MSP-1(19) was competitively inhibited by the anti-MSP-1(19) mouse monoclonal antibody 12.8, which inhibits erythrocyte invasion by merozoites. However, the human Fab fragment with the highest affinity did not inhibit in vitro growth of P. falciparum. This is the first report of gene analysis and bacterial expression of human monoclonal antibodies to P. falciparum MSP-1(19). The combinatorial immunoglobulin gene library derived from malaria patients provides a potential tool for producing high-affinity human antibodies specific for P. falciparum.",,"['Cheng, Xun-Jia', 'Hayasaka, Hitoshi', 'Watanabe, Katsuomi', 'Tao, Yan-Lin', 'Liu, Jin-Ye', 'Tsukamoto, Hideo', 'Horii, Toshihiro', 'Tanabe, Kazuyuki', 'Tachibana, Hiroshi']",,,,
,PMC,SARS-CoV Replication and Pathogenesis in an In Vitro Model of the Human Conducting Airway Epithelium,http://dx.doi.org/10.1016/j.virusres.2007.03.013,PMC2384224,,,"SARS coronavirus (SARS-CoV) emerged in 2002 as an important cause of severe lower respiratory tract infection in humans and in vitro models of the lung are needed to elucidate cellular targets and the consequences of viral infection. The severe and sudden onset of symptoms, resulting in an atypical pneumonia with dry cough and persistent high fever in cases of severe acute respiratory virus brought to light the importance of coronaviruses as potentially lethal human pathogens and the identification of several zoonotic reservoirs has made the reemergence of new strains and future epidemics all the more possible. In this chapter, we describe the pathology of SARS-CoV infection in humans and explore the use of two models of the human conducting airway to develop a better understanding of the replication and pathogenesis of SARS-CoV in relevant in vitro systems. The first culture model is a human bronchial epithelial cell line Calu3 that can be inoculated by viruses either as a non-polarized monolayer of cells or polarized cells with tight junctions and microvilli. The second model system, derived from primary cells isolated from human airway epithelium and grown on Transwells, form a pseudostratified mucociliary epithelium that recapitulates the morphological and physiological features of the human conducting airway in vivo. Experimental results using these lung epithelial cell models demonstrate that in contrast to the pathology reported in late stage cases SARS-CoV replicates to high titers in epithelial cells of the conducting airway. The SARS-CoV receptor, human angiotensin 1 converting enzyme 2 (hACE2), was detected exclusively on the apical surface of cells in polarized Calu3 cells and human airway epithelial cultures (HAE), indicating that hACE2 was accessible by SARS-CoV after airway lumenal delivery. Furthermore, in HAE, hACE2 was exclusively localized to ciliated airway epithelial cells. In support of the hACE2 localization data, the most productive route of inoculation and progeny virion egress in both polarized Calu3 and ciliated cells of HAE was the apical surface suggesting mechanisms to release large quantities of virus into the lumen of the human lung. Preincubation of the apical surface of cultures with antisera directed against hACE2 reduced viral titers by 2 logs while antisera against DC-SIGN/DC-SIGNR did not reduce viral replication levels suggesting that hACE2 is the primary receptor for entry of SARS-CoV into the ciliated cells of HAE cultures. To assess infectivity in ciliated airway cultures derived from susceptible animal species we generated a recombinant SARS-CoV by deletion of open reading frame 7a/7b (ORF 7a/b) and insertion of the green fluorescent protein (GFP) resulting in SARS-CoV GFP. SARS-CoV GFP replicated to similar titers as wild type viruses in Vero E6, MA104, and CaCo2 cells. In addition, SARS-CoV replication in airway epithelial cultures generated from Golden Syrian hamster tracheas reached similar titers to the human cultures by 72 hours post infection. Efficient SARS-CoV infection of ciliated cell-types in HAE provides a useful in vitro model of human lung origin to study characteristics of SARS-CoV replication and pathogenesis.",,"['Sims, Amy C.', 'Burkett, Susan E.', 'Yount, Boyd', 'Pickles, Raymond J.']",,,,
,PMC,SARS CORONAVIRUS AND INNATE IMMUNITY,http://dx.doi.org/10.1016/j.virusres.2007.03.015,PMC2292640,,,"The emergence of the highly pathogenic SARS coronavirus (SARS-CoV) has reignited interest in coronavirus biology and pathogenesis. An emerging theme in coronavirus pathogenesis is that the interaction between specific viral genes and the host immune system, specifically the innate immune system, functions as a key determinant in regulating virulence and disease outcomes. Using SARS-CoV as a model, we will review the current knowledge of the interplay between coronavirus infection and the host innate immune system in vivo, and then discuss the mechanisms by which specific gene products antagonize the host innate immune response in cell culture models. Our data suggests that the SARS-CoV uses specific strategies to evade and antagonize the sensing and signaling arms of the interferon pathway. We summarize by identifying future points of consideration that will contribute greatly to our understanding of the molecular mechanisms governing coronavirus pathogenesis and virulence, and the development of severe disease in humans and animals.",,"['Frieman, Matthew', 'Heise, Mark', 'Baric., Ralph']",,,,
,PMC,A systematic bioinformatics approach for selection of epitope-based vaccine targets,http://dx.doi.org/10.1016/j.cellimm.2007.02.005,PMC2041846,,,"Epitope-based vaccines provide a new strategy for prophylactic and therapeutic application of pathogen-specific immunity. A critical requirement of this strategy is the identification and selection of T-cell epitopes that act as vaccine targets. This study describes current methodologies for the selection process, with dengue virus as a model system. A combination of publicly available bioinformatics algorithms and computational tools are used to screen and select antigen sequences as potential T-cell epitopes of supertype HLA alleles. The selected sequences are tested for biological function by their activation of T-cells of HLA transgenic mice and of pathogen infected subjects. This approach provides an experimental basis for the design of pathogen specific, T-cell epitope-based vaccines that are targeted to majority of the genetic variants of the pathogen, and are effective for a broad range of differences in human leukocyte antigens among the global human population.",,"['Khan, Asif M.', 'Miotto, Olivo', 'Heiny, A.T.', 'Salmon, Jerome', 'Srinivasan, K.N.', 'Nascimento, Eduardo', 'Marques, Ernesto T.', 'Brusic, Vladimir', 'Tan, Tin Wee', 'August, J. Thomas']",,,,
,PMC,Environmental effects on parasitic disease transmission exemplified by schistosomiasis in western China,http://dx.doi.org/10.1073/pnas.0701878104,PMC1852328,,,"Environmental effects on the transmission of many parasitic diseases are well recognized, but the role of specific factors like climate and agricultural practices in modulating transmission is seldom characterized quantitatively. Based on studies of Schistosoma japonicum transmission in irrigated agricultural environments in western China, a mathematical model was used to quantify environmental impacts on transmission intensity. The model was calibrated by using field data from intervention studies in three villages and simulated to predict the effects of alternative control options. Both the results of these interventions and earlier epidemiological findings confirm the central role of environmental factors, particularly those relating to snail habitat and agricultural and sanitation practices. Moreover, the findings indicate the inadequacy of current niclosamide-praziquantel strategies alone to achieve sustainable interruption of transmission in some endemic areas. More generally, the analysis suggests a village-specific index of transmission potential and how this potential is modulated by time-varying factors, including climatological variables, seasonal water-contact patterns, and irrigation practices. These time-variable factors, a village's internal potential, and its connectedness to its neighbors provide a framework for evaluating the likelihood of sustained schistosomiasis transmission and suggest an approach to quantifying the role of environmental factors for other parasitic diseases.",,"['Liang, Song', 'Seto, Edmund Y. W.', 'Remais, Justin V.', 'Zhong, Bo', 'Yang, Changhong', 'Hubbard, Alan', 'Davis, George M.', 'Gu, Xueguang', 'Qiu, Dongchuan', 'Spear, Robert C.']",,,,
,PMC,Ebola virus-like particle-induced activation of NF-κB and Erk signaling in human dendritic cells requires the glycoprotein mucin domain,http://dx.doi.org/10.1016/j.virol.2007.03.020,PMC2034500,,,"Dendritic cells (DCs), important early targets of Ebola virus (EBOV) infection in vivo, are activated by Ebola virus-like particles (VLPs). To better understand this phenomenon, we have systematically assessed the response of DCs to VLPs of different compositions. VLPs containing the viral matrix protein (VP40) and the viral glycoprotein (GP), were found to induce a proinflammatory response highly similar to a prototypical DC activator, LPS. This response included the production of several proinflammatory cytokines, activation of numerous transcription factors including NF-kappaB, the functional importance of which was demonstrated by employing inhibitors of NF-kappaB activation, and activation of ERK1/2 MAP kinase. In contrast, VLPs constituted with a mutant GP lacking the heavily glycosylated mucin domain showed impaired NF-kappaB and Erk activation and induced less DC cytokine production. We conclude that the GP mucin domain is required for VLPs to stimulate human dendritic cells through NF-kappaB and MAPK signaling pathways.",,"['Martinez, Osvaldo', 'Valmas, Charalampos', 'Basler, Christopher F.']",,,,
,PMC,Neurokinin-1 enables measles virus trans-synaptic spread in neurons,http://dx.doi.org/10.1016/j.virol.2007.02.033,PMC1945128,,,"Measles virus (MV), a morbillivirus that remains a significant human pathogen, can infect the central nervous system, resulting in rare but often fatal diseases, such as subacute sclerosing panencephalitis. Previous work demonstrated that MV was transmitted trans-synaptically, and that, while a cellular receptor for the hemagglutinin (H) protein was required for MV entry, it was dispensable for subsequent cell-to-cell spread. Here, we explored what role the other envelope protein, fusion (F), played in trans-synaptic transport. We made the following observations: 1) MV-F expression in infected neurons was similar to that seen in infected fibroblasts; 2) fusion inhibitory peptide (FIP), an inhibitor of MV fusion, prevented both infection and spread in primary neurons; 3) Substance P, a neurotransmitter with the same active site as FIP, also blocked neuronal MV spread; and 4) both genetic deletion and pharmacological inhibition of the Substance P receptor, neurokinin-1 (NK-1), reduced infection of susceptible mice. Together, these data implicate a role for NK-1 in MV CNS infection and spread, perhaps serving as a MVF receptor or co-receptor on neurons.",,"['Makhortova, Nina', 'Askovich, Peter', 'Patterson, Catherine E.', 'Gechman, Lisa A.', 'Gerard, Norma P.', 'Rall, Glenn F.']",,,,
,PMC,Stockpiling smallpox virus,http://dx.doi.org/10.1136/bmj.39177.580729.BE,PMC1852028,,,"Other viruses pose greater public health threats, so isn't it time to move on?",,"Mack, Thomas",,,,
,PMC,Inhibitory effect of vascular endothelial growth factors-targeted small interfering RNA on proliferation of gastric cancer cells,http://dx.doi.org/10.3748/wjg.v13.i14.2044,PMC4319122,,,"AIM: To examine the effects of vascular endothelial growth factor (VEGF)-targeted small interfering RNA (siRNA) on proliferation of gastric cancer cells in vitro. METHODS: Several siRNAs were transfected into human gastric cancer cell line SGC-7901 with Lipofectamine 2000. Cells not transfected with Lipofectamine(TM) 2000 or scrambled (SCR) siRNA served as controls. The inhibitory effect of siRNA on the expression of VEGF mRNA and protein was detected by RT-PCR and ELISA. MTT assay was used to examine the inhibition rate of cell growth. The change in cell cycling of siRNA-treated cells was detected by flow cytometry. RESULTS: siRNA targeting human VEGF effectively inhibited the proliferation of gastric cancer cell line SGC-7901 and the distribution of cell cycle. The percentage of G(0)/G(1) phase was significantly higher in siRNA(1)- and siRNA(2)-transfected cells than in control cells. The expression of VEGF mRNA was significantly inhibited in siRNA(1)- and siRNA(2)-transfected cells compared with that in control cells. VEGF protein notably decreased in siRNA-transfected cells, but had no effect on SCR siRNA. CONCLUSION: VEGF siRNA inhibits proliferation of gastric cancer cells in vitro.",,"['Xu, Wen-Hua', 'Ge, Yin-Lin', 'Li, Quan', 'Zhang, Xiao', 'Duan, Jian-Hua']",,,,
,PMC,Analysis of Murine Hepatitis Virus Strain A59 Temperature-Sensitive Mutant TS-LA6 Suggests that nsp10 Plays a Critical Role in Polyprotein Processing,http://dx.doi.org/10.1128/JVI.00049-07,PMC1933295,,,"Coronaviruses are the largest RNA viruses, and their genomes encode replication machinery capable of efficient replication of both positive- and negative-strand viral RNAs as well as enzymes capable of processing large viral polyproteins into putative replication intermediates and mature proteins. A model described recently by Sawicki et al. (S. G. Sawicki, D. L. Sawicki, D. Younker, Y. Meyer, V. Thiel, H. Stokes, and S. G. Siddell, PLoS Pathog. 1:e39, 2005), based upon complementation studies of known temperature-sensitive (TS) mutants of murine hepatitis virus (MHV) strain A59, proposes that an intermediate comprised of nsp4 to nsp10/11 (∼150 kDa) is involved in negative-strand synthesis. Furthermore, the mature forms of nsp4 to nsp10 are thought to serve as cofactors with other replicase proteins to assemble a larger replication complex specifically formed to transcribe positive-strand RNAs. In this study, we introduced a single-amino-acid change (nsp10:Q65E) associated with the TS-LA6 phenotype into nsp10 of the infectious clone of MHV. Growth kinetic studies demonstrated that this mutation was sufficient to generate the TS phenotype at permissive and nonpermissive temperatures. Our results demonstrate that the TS mutant variant of nsp10 inhibits the main protease, 3CLpro, blocking its function completely at the nonpermissive temperature. These results implicate nsp10 as being a critical factor in the activation of 3CLpro function. We discuss how these findings challenge the current hypothesis that nsp4 to nsp10/11 functions as a single cistron in negative-strand RNA synthesis and analyze recent complementation data in light of these new findings.",,"['Donaldson, Eric F.', 'Graham, Rachel L.', 'Sims, Amy C.', 'Denison, Mark R.', 'Baric, Ralph S.']",,,,
,PMC,New Structure Model for the Packaging Signal in the Genome of Group IIa Coronaviruses,http://dx.doi.org/10.1128/JVI.02231-06,PMC1900089,,,"A 190-nucleotide (nt) packaging signal (PS) located in the 3′ end of open reading frame 1b in the mouse hepatitis virus, a group IIa coronavirus, was previously postulated to direct genome RNA packaging. Based on phylogenetic data and structure probing, we have identified a 95-nt hairpin within the 190-nt PS domain which is conserved in all group IIa coronaviruses but not in the severe acute respiratory syndrome coronavirus (group IIb), group I coronaviruses, or group III coronaviruses. The hairpin is composed of six copies of a repeating structural subunit that consists of 2-nt bulges and 5-bp stems. We propose that repeating AA bulges are characteristic features of group IIa PSs.",,"['Chen, Shih-Cheng', 'van den Born, Erwin', 'van den Worm, Sjoerd H. E.', 'Pleij, Cornelis W. A.', 'Snijder, Eric J.', 'Olsthoorn, René C. L.']",,,,
,PMC,Induction of Apoptosis by the Severe Acute Respiratory Syndrome Coronavirus 7a Protein Is Dependent on Its Interaction with the Bcl-X(L) Protein,http://dx.doi.org/10.1128/JVI.00090-07,PMC1900074,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) 7a protein, which is not expressed by other known coronaviruses, can induce apoptosis in various cell lines. In this study, we show that the overexpression of Bcl-X(L), a prosurvival member of the Bcl-2 family, blocks 7a-induced apoptosis, suggesting that the mechanism for apoptosis induction by 7a is at the level of or upstream from the Bcl-2 family. Coimmunoprecipitation experiments showed that 7a interacts with Bcl-X(L) and other prosurvival proteins (Bcl-2, Bcl-w, Mcl-1, and A1) but not with the proapoptotic proteins (Bax, Bak, Bad, and Bid). A good correlation between the abilities of 7a deletion mutants to induce apoptosis and to interact with Bcl-X(L) was observed, suggesting that 7a triggers apoptosis by interfering directly with the prosurvival function of Bcl-X(L). Interestingly, amino acids 224 and 225 within the C-terminal transmembrane domain of Bcl-X(L) are essential for the interaction with the 7a protein, although the BH3 domain of Bcl-X(L) also contributes to this interaction. In addition, fractionation experiments showed that 7a colocalized with Bcl-X(L) at the endoplasmic reticulum as well as the mitochondria, suggesting that they may form complexes in different membranous compartments.",,"['Tan, Ying-Xim', 'Tan, Timothy H. P.', 'Lee, Marvin J.-R.', 'Tham, Puay-Yoke', 'Gunalan, Vithiagaran', 'Druce, Julian', 'Birch, Chris', 'Catton, Mike', 'Fu, Nai Yang', 'Yu, Victor C.', 'Tan, Yee-Joo']",,,,
,PMC,Differential P(1) arginine and lysine recognition in the prototypical proprotein convertase Kex2,http://dx.doi.org/10.1073/pnas.0701983104,PMC1871836,,,"The high-resolution crystal structure of kexin (Kex2) in complex with a peptidyl-chloromethylketone inhibitor containing a noncognate lysine at the P(1) position provides the structural basis for the differential lysine/arginine selectivity that defines the prohormone (proprotein) convertase (PC) family. By comparison with the previous structures of Kex2 and furin, this structure of the acylated enzyme provides a basis for the observed decrease in the acylation rate with substrates containing a lysine at P(1) and the absence of an effect on the deacylation rate without involving mobility of the S(1) lid. The structure of the complex shows that a secondary subsite in the S(1) pocket is present, and that this site recognizes and binds the P(1) lysine in a more shallow fashion than arginine. This results in a displacement of the bound peptide away from the S385 nucleophile relative to substrates containing a P(1) arginine. It is concluded that this alternate binding site and resultant displacement of the scissile bond in the active site results in the observed decrease in the acylation rate. Studies of the inactivation kinetics of Kex2 by two peptidyl chloromethylketone inhibitors demonstrates that the selectivity between lysine and arginine at the P(1) position arises at the acylation step, consistent with what was observed with peptidyl substrates [Rockwell NC, Fuller RS (2001) J Biol Chem 276:38394–38399].",,"['Wheatley, Joshua L.', 'Holyoak, Todd']",,,,
,PMC,Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease,http://dx.doi.org/10.1016/j.virusres.2007.01.021,PMC2633062,,,"An important effort has been performed after the emergence of severe acute respiratory syndrome (SARS) epidemic in 2003 to diagnose and prevent virus spreading. Several types of vaccines have been developed including inactivated viruses, subunit vaccines, virus-like particles (VLPs), DNA vaccines, heterologous expression systems, and vaccines derived from SARS-CoV genome by reverse genetics. This review describes several aspects essential to develop SARS-CoV vaccines, such as the correlates of protection, virus serotypes, vaccination side effects, and bio-safeguards that can be engineered into recombinant vaccine approaches based on the SARS-CoV genome. The production of effective and safe vaccines to prevent SARS has led to the development of promising vaccine candidates, in contrast to the design of vaccines for other coronaviruses, that in general has been less successful. After preclinical trials in animal models, efficacy and safety evaluation of the most promising vaccine candidates described has to be performed in humans.",,"['Enjuanes, Luis', 'DeDiego, Marta L.', 'Álvarez, Enrique', 'Deming, Damon', 'Sheahan, Tim', 'Baric, Ralph']",,,,
,PMC,English government consults on new law to reduce spread of infection,http://dx.doi.org/10.1136/bmj.39170.633252.DB,PMC1847892,,,,,"Mayor, Susan",,,,
,PMC,The effect of public health measures on the 1918 influenza pandemic in U.S. cities,http://dx.doi.org/10.1073/pnas.0611071104,PMC1849868,,,"During the 1918 influenza pandemic, the U.S., unlike Europe, put considerable effort into public health interventions. There was also more geographic variation in the autumn wave of the pandemic in the U.S. compared with Europe, with some cities seeing only a single large peak in mortality and others seeing double-peaked epidemics. Here we examine whether differences in the public health measures adopted by different cities can explain the variation in epidemic patterns and overall mortality observed. We show that city-specific per-capita excess mortality in 1918 was significantly correlated with 1917 per-capita mortality, indicating some intrinsic variation in overall mortality, perhaps related to sociodemographic factors. In the subset of 23 cities for which we had partial data on the timing of interventions, an even stronger correlation was found between excess mortality and how early in the epidemic interventions were introduced. We then fitted an epidemic model to weekly mortality in 16 cities with nearly complete intervention-timing data and estimated the impact of interventions. The model reproduced the observed epidemic patterns well. In line with theoretical arguments, we found the time-limited interventions used reduced total mortality only moderately (perhaps 10–30%), and that the impact was often very limited because of interventions being introduced too late and lifted too early. San Francisco, St. Louis, Milwaukee, and Kansas City had the most effective interventions, reducing transmission rates by up to 30–50%. Our analysis also suggests that individuals reactively reduced their contact rates in response to high levels of mortality during the pandemic.",,"['Bootsma, Martin C. J.', 'Ferguson, Neil M.']",,,,
,PMC,"Evaluation of a Commercial Real-Time PCR Kit for Detection of Dengue Virus in Samples Collected during an Outbreak in Goiânia, Central Brazil, in 2005",http://dx.doi.org/10.1128/JCM.00065-07,PMC1933102,,,"In the past 2 decades, dengue has reemerged in Brazil as a significant public health problem. Clinicians demand a diagnostic test with high sensitivity that is applicable during the early symptomatic phase. We aimed to test two distinct molecular methods on samples from suspected dengue cases during an outbreak in Central Brazil. Acute-phase serum specimens from 254 patients suspected of having dengue were collected during 2005 in the city of Goiânia, Central Brazil. Samples were blindly evaluated by real-time and multiplex PCR in addition to routine immunoglobulin M serology and virus culture. Overall, acute dengue was confirmed by serology, multiplex PCR, or virus isolation for 80% of patients (203/254). Another four patients presented real-time PCR-positive results as the unique marker of dengue. Higher real-time PCR positivity levels and viral loads were observed in the early symptomatic phase of disease (≤5 days) than after this period. Multiplex and real-time PCR assays presented a high kappa agreement (0.85). According to multiplex PCR, 60 samples harbored dengue virus type 3 (DEN-3), 4 samples harbored DEN-2, and 1 sample displayed a pattern compatible with a double infection with DEN-2 and -3. The dengue virus real-time kit was found to be practical and adjustable for high throughput, to display the best performance in the early symptomatic phase of dengue cases, and to be valuable for confirming dengue diagnosis in a timely manner.",,"['Levi, José Eduardo', 'Tateno, Adriana Fumie', 'Machado, Adriana Freire', 'Ramalho, Débora Camillo', 'de Souza, Vanda Akico Ueda Fick', 'Guilarde, Adriana Oliveira', 'de Rezende Feres, Valéria Christina', 'Martelli, Celina Maria Turchi', 'Turchi, Marília Dalva', 'Siqueira, João Bosco', 'Pannuti, Cláudio Sérgio']",,,,
,PMC,Crystal Structure of a Monomeric Form of Severe Acute Respiratory Syndrome Coronavirus Endonuclease nsp15 Suggests a Role for Hexamerization as an Allosteric Switch,http://dx.doi.org/10.1128/JVI.02817-06,PMC1900129,,,"Mature nonstructural protein-15 (nsp15) from the severe acute respiratory syndrome coronavirus (SARS-CoV) contains a novel uridylate-specific Mn(2+)-dependent endoribonuclease (NendoU). Structure studies of the full-length form of the obligate hexameric enzyme from two CoVs, SARS-CoV and murine hepatitis virus, and its monomeric homologue, XendoU from Xenopus laevis, combined with mutagenesis studies have implicated several residues in enzymatic activity and the N-terminal domain as the major determinant of hexamerization. However, the tight link between hexamerization and enzyme activity in NendoUs has remained an enigma. Here, we report the structure of a trimmed, monomeric form of SARS-CoV nsp15 (residues 28 to 335) determined to a resolution of 2.9 Å. The catalytic loop (residues 234 to 249) with its two reactive histidines (His 234 and His 249) is dramatically flipped by ∼120° into the active site cleft. Furthermore, the catalytic nucleophile Lys 289 points in a diametrically opposite direction, a consequence of an outward displacement of the supporting loop (residues 276 to 295). In the full-length hexameric forms, these two loops are packed against each other and are stabilized by intimate intersubunit interactions. Our results support the hypothesis that absence of an adjacent monomer due to deletion of the hexamerization domain is the most likely cause for disruption of the active site, offering a structural basis for why only the hexameric form of this enzyme is active.",,"['Joseph, Jeremiah S.', 'Saikatendu, Kumar Singh', 'Subramanian, Vanitha', 'Neuman, Benjamin W.', 'Buchmeier, Michael J.', 'Stevens, Raymond C.', 'Kuhn, Peter']",,,,
,PMC,Lassa Virus Infection in Experimentally Infected Marmosets: Liver Pathology and Immunophenotypic Alterations in Target Tissues,http://dx.doi.org/10.1128/JVI.02876-06,PMC1900113,,,"Lassa virus causes thousands of deaths annually in western Africa and is considered a potential biological weapon. In an attempt to develop a small nonhuman primate model of Lassa fever, common marmosets were subcutaneously inoculated with Lassa virus strain Josiah. This inoculation resulted in a systemic disease with clinical and morphological features mirroring those in fatal human Lassa infection: fever, weight loss, high viremia and viral RNA load in tissues, elevated liver enzymes, and severe morbidity between days 15 and 20. The most prominent histopathology findings included multifocal hepatic necrosis with mild inflammation and hepatocyte proliferation, lymphoid depletion, and interstitial nephritis. Cellular aggregates in regions of hepatocellular necrosis were largely composed of HAM56-positive macrophages, devoid of CD3-positive and CD20-positive cells, and characterized by marked reductions in the intensity of HLA-DP, DQ, DR staining. A marked reduction in the major histocompatibility complex class II expression was also observed in the lymph nodes. Immunophenotypic alterations in spleen included reductions in overall numbers of CD20-positive and CD3-positive cells and the disruption of lymphoid follicular architecture. These findings identify the common marmoset as an appropriate model of human Lassa fever and present the first experimental evidence that replication of Lassa virus in tissues is associated with alterations that would be expected to impair adaptive immunity.",,"['Carrion, Ricardo', 'Brasky, Kathleen', 'Mansfield, Keith', 'Johnson, Curtis', 'Gonzales, Monica', 'Ticer, Anysha', 'Lukashevich, Igor', 'Tardif, Suzette', 'Patterson, Jean']",,,,
,PMC,"Transmissibility of swine flu at Fort Dix, 1976",http://dx.doi.org/10.1098/rsif.2007.0228,PMC2373398,,,"The 1976 outbreak of A/New Jersey/76 influenza in Fort Dix is a rare example of an influenza virus with documented human to human transmission that failed to spread widely. Despite extensive epidemiological investigation, no attempt has been made to quantify the transmissibility of this virus. The World Health Organization and the United States Government view containment of emerging influenza strains as central to combating pandemic influenza. Computational models predict that it may be possible to contain an emergent pandemic influenza if virus transmissibility is low. The A/New Jersey/76 outbreak at the United States Army Training Center at Fort Dix, New Jersey in January 1976 caused 13 hospitalizations, 1 death and an estimated 230 cases. To characterize viral transmission in this epidemic, we estimated the basic reproductive number and serial interval using deterministic epidemic models and stochastic simulations. We estimated the basic reproductive number for this outbreak to be 1.2 (supported interval 1.1–1.4), the serial interval to be 1.9 days (supported interval 1.6–3.8 days), and that the virus had at least six serial human to human transmissions. This places the transmissibility of A/New Jersey/76 virus at the lower end of circulating flu strains, well below the threshold for control.",,"['Lessler, Justin', 'Cummings, Derek A.T', 'Fishman, Steven', 'Vora, Amit', 'Burke, Donald S']",,,,
,PMC,Strong and Selective Inhibitors of Hepatitis B Virus Replication among Novel N(4)-Hydroxy- and 5-Methyl-β-l-Deoxycytidine Analogues,http://dx.doi.org/10.1128/AAC.00001-07,PMC1913238,,,"Novel N(4)-hydroxy- and 5-methyl-modified β-l-deoxycytidine analogues were synthesized and evaluated as anti-hepatitis B virus (HBV) agents. Their in vitro efficiencies were investigated in HepG2.2.15 cells stably transfected with HBV. β-l-2′,3′-Didehydro-2′,3′-dideoxy-N(4)-hydroxycytidine (β-l-Hyd4C) was most effective in reducing secreted HBV DNA (50% effective concentration [EC(50)], 0.03 μM), followed by β-l-2′,3′-dideoxy-3′-thia-N(4)-hydroxycytidine (EC(50), 0.51 μM), β-l-2′,3′-dideoxy-N(4)-hydroxycytidine (EC(50), 0.55 μM), and β-l-5-methyl-2′-deoxycytidine (EC(50), 0.9 μM). The inhibition of the presumed target, the HBV DNA polymerase, by the triphosphates of some of the β-l-cytidine derivatives was also assessed. In accordance with the cell culture data, β-l-Hyd4C triphosphate was the most active inhibitor, with a 50% inhibitory concentration of 0.21 μM. The cytotoxicities of some of the 4-NHOH-modified β-l-nucleosides were dramatically lower than those of the corresponding cytidine analogues with the unmodified 4-NH(2) group. The 50% cytotoxic concentrations for β-l-Hyd4C in HepG2 and HL-60 cells were 2,500 μM and 3,500 μM, respectively. In summary, our results demonstrate that at least β-l-Hyd4C can be recommended as a highly efficient and extremely selective inhibitor of HBV replication for further investigations.",,"['Matthes, E.', 'Funk, A.', 'Krahn, I.', 'Gaertner, K.', 'von Janta-Lipinski, M.', 'Lin, L.', 'Will, H.', 'Sirma, H.']",,,,
,PMC,Pathology and Pathogenesis of Severe Acute Respiratory Syndrome,http://dx.doi.org/10.2353/ajpath.2007.061088,PMC1829448,,,"Severe acute respiratory syndrome (SARS) is an emerging infectious viral disease characterized by severe clinical manifestations of the lower respiratory tract. The pathogenesis of SARS is highly complex, with multiple factors leading to severe injury in the lungs and dissemination of the virus to several other organs. The SARS coronavirus targets the epithelial cells of the respiratory tract, resulting in diffuse alveolar damage. Several organs/cell types may be infected in the course of the illness, including mucosal cells of the intestines, tubular epithelial cells of the kidneys, neurons of the brain, and several types of immune cells, and certain organs may suffer from indirect injury. Extensive studies have provided a basic understanding of the pathogenesis of this disease. In this review we describe the most significant pathological features of SARS, explore the etiological factors causing these pathological changes, and discuss the major pathogenetic mechanisms. The latter include dysregulation of cytokines/chemokines, deficiencies in the innate immune response, direct infection of immune cells, direct viral cytopathic effects, down-regulation of lung protective angiotensin converting enzyme 2, autoimmunity, and genetic factors. It seems that both abnormal immune responses and injury to immune cells may be key factors in the pathogenesis of this new disease.",,"['Gu, Jiang', 'Korteweg, Christine']",,,,
,PMC,The Law and Emergencies: Surveillance for Public Health–Related Legal Issues During Hurricanes Katrina and Rita,http://dx.doi.org/10.2105/AJPH.2006.104240,PMC1855002,,,"Law influenced every aspect of the public health response to Hurricanes Katrina and Rita, from evacuation orders, to waivers of medical licensing requirements, to the clean-up of public health threats on private property. We used public health surveillance of news reports to identify and characterize legal issues arising during the disaster response in 5 Gulf Coast states. Data collected from news reports of the events in real time were followed-up by interviews with selected state legal and emergency management officials. Our analysis indicates the value of surveillance during and after emergency responses in identifying public health–related legal issues and helps to inform the strengthening of legal preparedness frameworks for future disasters.",,"['Weiss, Rachel I.', 'McKie, Karen L.', 'Goodman, Richard A.']",,,,
,PMC,Optimizing Severe Acute Respiratory Syndrome Response Strategies: Lessons Learned From Quarantine,http://dx.doi.org/10.2105/AJPH.2005.082115,PMC1855001,,,"Taiwan used quarantine as 1 of numerous interventions implemented to control the outbreak of severe acute respiratory syndrome in 2003. From March 18 to July 31, 2003, 147 526 persons were placed under quarantine. Quarantining only persons with known exposure to people infected with severe acute respiratory syndrome could have reduced the number of persons quarantined by approximately 64%. Focusing quarantine efforts on persons with known or suspected exposure can greatly decrease the number of persons placed under quarantine, without substantially compromising its yield and effectiveness.",,"['Wang, Tsung-Hsi', 'Wei, Kuo-Chen', 'Hsiung, Chao Agnes', 'Maloney, Susan A.', 'Eidex, Rachel Barwick', 'Posey, Drew L.', 'Chou, Wei-Hui', 'Shih, Wen-Yi', 'Kuo, Hsu-Sung']",,,,
,PMC,Encouraging Compliance With Quarantine: A Proposal to Provide Job Security and Income Replacement,http://dx.doi.org/10.2105/AJPH.2006.097303,PMC1854999,,,"A human influenza virus is considered the most likely source of a pandemic in the near future. Quarantine has the potential to be the most effective measure for limiting the spread of infection. The major obstacles to compliance for those asked to enter quarantine include loss of income during quarantine and loss of employment after quarantine. We discuss current antidiscrimination and compensation laws, as well as options to expand coverage for quarantined individuals to encourage public cooperation by guaranteeing job security and providing income replacement.",,"['Rothstein, Mark A.', 'Talbott, Meghan K.']",,,,
,PMC,Disrupting the Transmission of Influenza A: Face Masks and Ultraviolet Light as Control Measures,http://dx.doi.org/10.2105/AJPH.2006.096214,PMC1854994,,,"In the event of an influenza pandemic, where effective vaccine and antiviral drugs may be lacking, disrupting environmental transmission of the influenza virus will be the only viable strategy to protect the public. We discuss 2 such modalities, respirators (face masks) and ultraviolet (UV) light. Largely overlooked, the potential utility of each is underappreciated. The effectiveness of disposable face masks may be increased by sealing the edges of the mask to the face. Reusable masks should be stockpiled, because the supply of disposable masks will likely prove inadequate. UV light, directed overhead, may be beneficial in hospitals and nursing homes.",,"['Weiss, Martin Meyer', 'Weiss, Peter D.', 'Weiss, Danielle E.', 'Weiss, Joseph B.']",,,,
,PMC,"The Courts, Public Health, and Legal Preparedness",http://dx.doi.org/10.2105/AJPH.2006.101881,PMC1854991,,,"The judicial branch’s key roles, as guardian of civil liberties and protector of the rule of law, can be acutely relevant during public health emergencies when courts may need to issue orders authorizing actions to protect public health or restraining public health actions that are determined to unduly interfere with civil rights. Legal preparedness for public health emergencies, therefore, necessitates an understanding of the court system and how courts are involved in public health issues. In this article we briefly describe the court system and then focus on what public health practitioners need to know about the judicial system in a public health emergency, including the courts’ roles and the consequent need to keep courts open during emergencies.",,"['Stier, Daniel D.', 'Nicks, Diane', 'Cowan, Gregory J.']",,,,
,PMC,Legal Tools for Preparedness and Response: Variation in Quarantine Powers Among the 10 Most Populous US States in 2004,http://dx.doi.org/10.2105/AJPH.2005.083311,PMC1854981,,,"From April 2004 through December 2004, we reviewed the express legal authorities of the 10 most populous US states to restrict the movement of persons to control communicable diseases. All 10 of the states possessed express legal authority to quarantine and isolate individuals, but the laws varied substantially. In the absence of declared emergencies, only 4 states had express authority to conduct area quarantine, and only 2 states had express authority to conduct group quarantine. During declared emergencies, 7 states had additional authorities for area quarantine. Express authorities are only part of states’ legal powers to employ such movement restrictions, but substantial variation in express authorities across states could present potential challenges for the coordination of large national or regional epidemics.",,"['Shaw, Frederic E.', 'McKie, Karen L.', 'Liveoak, Clint A.', 'Goodman, Richard A.', None]",,,,
,PMC,Ready or Not?,http://dx.doi.org/10.2105/AJPH.2007.109447,PMC1854978,,,,,"Colmers, John M.",,,,
,PMC,Evidence and Effectiveness in Decisionmaking for Quarantine,http://dx.doi.org/10.2105/AJPH.2005.077305,PMC1854977,,,"When public health decisionmakers turned to quarantine during the recent severe acute respiratory syndrome (SARS) epidemic, difficult questions were raised about the legitimacy and acceptability of restrictive measures to attain public health goals. SARS also brought to light how scientific uncertainty can permeate public health decisionmaking, leading us to think about the relationship between the adequacy of evidence of the effectiveness of an intervention and its role in the justification of public health action. In this article, we critically examine the role of evidence and effectiveness in decision-making for quarantine. It is our contention that the effectiveness of a public health intervention should not be defined exclusively in (absolute and objective) scientific terms but rather conceptualized relationally and normatively in public health decisionmaking.",,"['Bensimon, Cécile M.', 'Upshur, Ross E.G.']",,,,
,PMC,Mutual Aid Agreements: Essential Legal Tools for Public Health Preparedness and Response,http://dx.doi.org/10.2105/AJPH.2006.101626,PMC1854975,,,"Mutual aid is the sharing of supplies, equipment, personnel, and information across political boundaries. States must have agreements in place to ensure mutual aid to facilitate effective responses to public health emergencies and to detect and control potential infectious disease outbreaks. The 2005 hurricanes triggered activation of the Emergency Management Assistance Compact (EMAC), a mutual aid agreement among the 50 states, the District of Columbia, Puerto Rico, and the US Virgin Islands. Although EMAC facilitated the movement of an unprecedented amount of mutual aid to disaster areas, inadequacies in the response demonstrated a need for improvement. Mutual aid may also be beneficial in circumstances where EMAC is not activated. We discuss the importance of mutual aid, examine obstacles, and identify legal “gaps” that must be filled to strengthen preparedness.",,"['Stier, Daniel D.', 'Goodman, Richard A.']",,,,
,PMC,Assessing the Status of Partnerships Between Academic Institutions and Public Health Agencies,http://dx.doi.org/10.2105/AJPH.2005.083188,PMC1829347,,,"We identified, described, and defined models of academic institution–public health agency partnerships in Florida. The study involved a mixed-method research design using data collected from a survey of 67 county health department (CHD) administrators and directors in Florida, in-depth interviews of key informants, and reviews of relevant Florida statutes and other archival data providing context for the partnerships. Fifty-one of the CHDs (76%) participated in the survey. Most reported formal agreements involving 50 different academic institutions. The partnerships were perceived to enhance the local public health system’s capacity. Recommendations focus on the need for a multitiered system for recognition of the partnerships and expansion of federal support for partnership beyond existing approaches.",,"['Livingood, William C.', 'Goldhagen, Jeffrey', 'Little, William L.', 'Gornto, Jennifer', 'Hou, Tao']",,,,
,PMC,T-cell function is partially maintained in the absence of class IA phosphoinositide 3-kinase signaling,http://dx.doi.org/10.1182/blood-2006-07-038620,PMC1852227,,,"The class IA subgroup of phosphoinositide 3-kinase (PI3K) is activated downstream of antigen receptors, costimulatory molecules, and cytokine receptors on lymphocytes. Targeted deletion of individual genes for class IA regulatory subunits severely impairs the development and function of B cells but not T cells. Here we analyze conditional mutant mice in which thymocytes and T cells lack the major class IA regulatory subunits p85α, p55α, p50α, and p85β. These cells exhibit nearly complete loss of PI3K signaling downstream of the T-cell receptor (TCR) and CD28. Nevertheless, T-cell development is largely unperturbed, and peripheral T cells show only partial impairments in proliferation and cytokine production in vitro. Both genetic and pharmacologic experiments suggest that class IA PI3K signaling plays a limited role in T-cell proliferation driven by TCR/CD28 clustering. In vivo, class IA–deficient T cells provide reduced help to B cells but show normal ability to mediate antiviral immunity. Together these findings provide definitive evidence that class IA PI3K regulatory subunits are essential for a subset of T-cell functions while challenging the notion that this signaling mechanism is a critical mediator of costimulatory signals downstream of CD28.",,"['Deane, Jonathan A.', 'Kharas, Michael G.', 'Oak, Jean S.', 'Stiles, Linda N.', 'Luo, Ji', 'Moore, Travis I.', 'Ji, Hong', 'Rommel, Christian', 'Cantley, Lewis C.', 'Lane, Thomas E.', 'Fruman, David A.']",,,,
,PMC,SARS: how a global epidemic was stopped,http://dx.doi.org/10.2471/BLT.07.032763,PMC2636331,,,,,"Chew, Suok Kai",,,,
,PMC,Veterinary medicine for a world in crisis,,PMC1831513,,,,,"Leighton, Frederick A.",,,,
,PMC,Avian Influenza Virus (H5N1): a Threat to Human Health,http://dx.doi.org/10.1128/CMR.00037-06,PMC1865597,,,"Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes. Therefore, H5N1 virus has rightly received attention as a potential pandemic threat. However, it is noted that the pandemics of 1957 and 1968 did not arise from highly pathogenic influenza viruses, and the next pandemic may well arise from a low-pathogenicity virus. The rationale for particular concern about an H5N1 pandemic is not its inevitability but its potential severity. An H5N1 pandemic is an event of low probability but one of high human health impact and poses a predicament for public health. Here, we review the ecology and evolution of highly pathogenic avian influenza H5N1 viruses, assess the pandemic risk, and address aspects of human H5N1 disease in relation to its epidemiology, clinical presentation, pathogenesis, diagnosis, and management.",,"['Peiris, J. S. Malik', 'de Jong, Menno D.', 'Guan, Yi']",,,,
,PMC,Avoidable mortality by neighbourhood income in Canada: 25 years after the establishment of universal health insurance,http://dx.doi.org/10.1136/jech.2006.047092,PMC2652935,,,"AIM: To examine neighbourhood income differences in deaths amenable to medical care and public health over a 25‐year period after the establishment of universal insurance for doctors and hospital services in Canada. METHODS: Data for census metropolitan areas were obtained from the Canadian Mortality Database and population censuses for the years 1971, 1986, 1991 and 1996. Deaths amenable to medical care, amenable to public health, from ischaemic heart disease and from other causes were considered. Data on deaths were grouped into neighbourhood income quintiles on the basis of the census tract percentage of population below Canada's low‐income cut‐offs. RESULTS: From 1971 to 1996, differences between the richest and poorest quintiles in age‐standardised expected years of life lost amenable to medical care decreased 60% (p<0.001) in men and 78% (p<0.001) in women, those amenable to public health increased 0.7% (p = 0.94) in men and 20% (p = 0.55) in women, those lost from ischaemic heart disease decreased 58% in men and 38% in women, and from other causes decreased 15% in men and 9% in women. Changes in the age‐standardised expected years of life lost difference for deaths amenable to medical care were significantly larger than those for deaths amenable to public health or other causes for both men and women (p<0.001). CONCLUSIONS: Reductions in rates of deaths amenable to medical care made the largest contribution to narrowing socioeconomic mortality disparities. Continuing disparities in mortality from causes amenable to public health suggest that public health initiatives have a potentially important, but yet unrealised, role in further reducing mortality disparities in Canada.",,"['James, Paul D', 'Wilkins, Russell', 'Detsky, Allan S', 'Tugwell, Peter', 'Manuel, Douglas G']",,,,
,PMC,Public health preparedness: a systems‐level approach,http://dx.doi.org/10.1136/jech.2004.030783,PMC2652933,,,"Public health and emergency preparedness have become central concepts in the current restructuring of various regional‐, national‐ and global‐level public health and emergency management agencies and systems. In this article, a glossary of the most important terms and concepts currently pertaining to public health preparedness is provided with a focus on systems‐level and organisational issues.",,"['Moore, Spencer', 'Mawji, Al', 'Shiell, Alan', 'Noseworthy, Tom']",,,,
,PMC,An mRNA sequence derived from the yeast EST3 gene stimulates programmed +1 translational frameshifting,http://dx.doi.org/10.1261/rna.412707,PMC1831869,,,"Programmed translational frameshift sites are sequences in mRNAs that promote frequent stochastic changes in translational reading frame allowing expression of alternative forms of protein products. The EST3 gene of Saccharomyces cerevisiae, encoding a subunit of telomerase, uses a programmed +1 frameshift site in its expression. We show that the site is complex, consisting of a heptameric sequence at which the frameshift occurs and a downstream 27-nucleotide stimulator sequence that increases frameshifting eightfold. The stimulator appears to be modular, composed of at least three separable domains. It increases frameshifting only when ribosomes pause at the frameshift site because of a limiting supply of a cognate aminoacyl-tRNA and not when pausing occurs at a nonsense codon. These data suggest that the EST3 stimulator may modulate access by aminoacyl-tRNAs to the ribosomal A site by interacting with several targets in a ribosome paused during elongation.",,"['Taliaferro, Dwayne', 'Farabaugh, Philip J.']",,,,
,PMC,"Structure-Function Relationships of the Viral RNA-dependent RNA Polymerase: FIDELITY, REPLICATION SPEED, AND INITIATION MECHANISM DETERMINED BY A RESIDUE IN THE RIBOSE-BINDING POCKET",http://dx.doi.org/10.1074/jbc.M610090200,PMC2116994,,,"Studies of the RNA-dependent RNA polymerase (RdRp) from poliovirus (PV), 3Dpol, have shown that Asn-297 permits this enzyme to distinguish ribose from 2′-deoxyribose. All animal RNA viruses have Asn at the structurally homologous position of their polymerases, suggesting a conserved function for this residue. However, all prokaryotic RNA viruses have Glu at this position. In the presence of Mg(2+), the apparent affinity of Glu-297 3Dpol for 2′-deoxyribonucleotides was decreased by 6-fold relative to wild type without a substantial difference in the fidelity of 2′-dNMP incorporation. The fidelity of ribonucleotide misincorporation for Glu-297 3Dpol was reduced by 14-fold relative to wild type. A 4- to 11-fold reduction in the rate of ribonucleotide incorporation was observed. Glu-297 PV was unable to grow in HeLa cells due to a replication defect equivalent to that observed for a mutant PV encoding an inactive polymerase. Evaluation of the protein-(VPg)-primed initiation reaction showed that only half of the Glu-297 3Dpol initiation complexes were capable of producing VPg-pUpU product and that the overall yield of uridylylated VPg products was reduced by 20-fold relative to wild-type enzyme, a circumstance attributable to a reduced affinity for UTP. These studies identify the first RdRp derivative with a mutator phenotype and provide a mechanistic basis for the elevated mutation frequency of RNA phage relative to animal RNA viruses observed in culture. Although protein-primed initiation and RNA-primed elongation complexes employ the same polymerase active site, the functional differences reported here imply significant structural differences between these complexes.",,"['Korneeva, Victoria S.', 'Cameron, Craig E.']",,,,
,PMC,Evaluating the 3C-like protease activity of SARS-Coronavirus: Recommendations for Standardized Assays for Drug Discovery,http://dx.doi.org/10.1016/j.virusres.2007.02.015,PMC4036818,,,"Although the initial outbreaks of the deadly coronavirus that causes severe acute respiratory syndrome (SARS-CoV) were controlled by public health measures, the development of vaccines and antiviral agents for SARS-CoV is essential for improving control and treatment of future outbreaks. One potential target for SARS-CoV antiviral drug development is the 3C-like protease (3CLpro). This enzyme is an attractive target since it is essential for viral replication, and since there are now a number of high resolution x-ray structures of SARS-CoV 3CLpro available making structure-based drug-design possible. As a result, SARS-CoV 3CLpro has become the focus of numerous drug discovery efforts worldwide, but as a consequence, a variety of different 3CLpro expression constructs and kinetic assays have been independently developed making evaluation and comparison between potential inhibitors problematic. Here, we review the literature focusing on different SARS-CoV 3CLpro expression constructs and assays used to measure enzymatic activity. Moreover, we provide experimental evidence showing that the activity of 3CLpro enzymatic is significantly reduced when non-native sequences or affinity-tags are added to the N- or C-termini of the enzyme, or when the enzyme used in assays is at concentrations below the equilibrium dissociation constant of the 3CLpro dimer. We demonstrate for the first time the utility of a highly sensitive and novel Alexa488-QSY7 FRET-based peptide substrate designed for routine analysis and high-throughput screening, and show that kinetic constants determined from FRET-based assays that are uncorrected for inner-filter effects can lead to artifacts. Finally, we evaluated the effects of common assay components including DTT, NaCl, EDTA and DMSO on enzymatic activity, and we recommend standardized assay conditions and constructs for routine SARS-CoV 3CLpro assays to facilitate direct comparisons between SARS-CoV 3CLpro inhibitors under development worldwide.",,"['Grum-Tokars, Valerie', 'Ratia, Kiira', 'Begaye, Adrian', 'Baker, Susan C.', 'Mesecar, Andrew D.']",,,,
,PMC,SARS coronavirus replicase proteins in pathogenesis,http://dx.doi.org/10.1016/j.virusres.2007.02.017,PMC2637536,,,"Much progress has been made in understanding the role of structural and accessory proteins in the pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) infections. The SARS epidemic also brought new attention to the proteins translated from ORF1a and ORF1b of the input genome RNA, also known as the replicase/transcriptase gene. Evidence for change within the ORF1ab coding sequence during the SARS epidemic, as well as evidence from studies with other coronaviruses, indicates that it is likely that the ORF1ab proteins play roles in virus pathogenesis distinct from or in addition to functions directly involved in viral replication. Recent reverse genetic studies have confirmed that proteins of ORF1ab may be involved in cellular signaling and modification of cellular gene expression, as well as virulence by mechanisms yet to be determined. Thus, the evolution of the ORF1ab proteins may be determined as much by issues of host range and virulence as they are by specific requirements for intracellular replication.",,"['Graham, Rachel L.', 'Sparks, Jennifer S.', 'Eckerle, Lance D.', 'Sims, Amy C.', 'Denison, Mark R.']",,,,
,PMC,Operational Feasibility of Using Loop-Mediated Isothermal Amplification for Diagnosis of Pulmonary Tuberculosis in Microscopy Centers of Developing Countries,http://dx.doi.org/10.1128/JCM.02352-06,PMC1933042,,,"The characteristics of loop-mediated isothermal amplification (LAMP) make it a promising platform for the molecular detection of tuberculosis (TB) in developing countries. Here, we report on the first clinical evaluation of LAMP for the detection of pulmonary TB in microscopy centers in Peru, Bangladesh, and Tanzania to determine its operational applicability in such settings. A prototype LAMP assay with simplified manual DNA extraction was evaluated for accuracy and ease of use. The sensitivity of LAMP in smear- and culture-positive sputum specimens was 97.7% (173/177 specimens; 95% confidence interval [CI], 95.5 to 99.9%), and the sensitivity in smear-negative, culture-positive specimens was 48.8% (21/43 specimens; CI, 33.9 to 63.7%). The specificity in culture-negative samples was 99% (500/505 specimens; CI, 98.1 to 99.9%). The average hands-on time for testing six samples and two controls was 54 min, similar to that of sputum smear microscopy. The optimal amplification time was 40 min. No indeterminate results were reported, and the interreader variability was 0.4%. Despite the use of a single room without biosafety cabinets for all procedures, no DNA contamination was observed. The assay was robust, with high end-point stability and low rates of test failure. Technicians with no prior molecular experience easily performed the assay after 1 week of training, and opportunities for further simplification of the assay were identified.",,"['Boehme, Catharina C.', 'Nabeta, Pamela', 'Henostroza, German', 'Raqib, Rubhana', 'Rahim, Zeaur', 'Gerhardt, Martina', 'Sanga, Erica', 'Hoelscher, Michael', 'Notomi, Tsugunori', 'Hase, Tetsu', 'Perkins, Mark D.']",,,,
,PMC,Identification and Characterization of Dominant Helper T-Cell Epitopes in the Nucleocapsid Protein of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.02568-06,PMC1900298,,,"By using a series of overlapping synthetic peptides covering 98% of the amino acid sequence of the nucleocapsid protein (NP) of severe acute respiratory syndrome coronavirus (SARS-CoV), four helper T-cell (Th) epitopes (NP11, residues 11 to 25; NP51, residues 51 to 65; NP61, residues 61 to 75; and NP111, residues 111 to 125) in C57BL mice (H-2(b)), four (NP21, residues 21 to 35; NP91, residues 91 to 105; NP331, residues 331 to 345; and NP351, residues 351 to 365) in C3H mice (H-2(k)), and two (NP81, residues 81 to 95; and NP351, residues 351 to 365) in BALB/c mice (H-2(d)) have been identified. All of these peptides were able to stimulate the proliferation of NP-specific T-cell lines or freshly isolated lymph node cells from mice immunized with recombinant NP. Immunization of mice with synthetic peptides containing appropriate Th epitopes elicited strong cellular immunity in vivo, as evidenced by delayed-type hypersensitivity. Priming with the helper peptides (e.g., NP111 and NP351) significantly accelerated the immune response induced by recombinant NP, as determined by the production of NP-specific antibodies. When fused with a conserved neutralizing epitope (SP1143-1157) from the spike protein of SARS-CoV, NP111 and NP351 assisted in the production of high-titer neutralizing antibodies in vivo. These data provide useful insights regarding immunity against SARS-CoV and have the potential to help guide the design of peptide-based vaccines.",,"['Zhao, Jincun', 'Huang, Qianrong', 'Wang, Wei', 'Zhang, Yan', 'Lv, Ping', 'Gao, Xiao-Ming']",,,,
,PMC,Proteolytic Processing and Deubiquitinating Activity of Papain-Like Proteases of Human Coronavirus NL63,http://dx.doi.org/10.1128/JVI.02747-06,PMC1900296,,,"Human coronavirus NL63 (HCoV-NL63), a common human respiratory pathogen, is associated with both upper and lower respiratory tract disease in children and adults. Currently, no antiviral drugs are available to treat CoV infections; thus, potential drug targets need to be identified and characterized. Here, we identify HCoV-NL63 replicase gene products and characterize two viral papain-like proteases (PLPs), PLP1 and PLP2, which process the viral replicase polyprotein. We generated polyclonal antisera directed against two of the predicted replicase nonstructural proteins (nsp3 and nsp4) and detected replicase proteins from HCoV-NL63-infected LLC-MK2 cells by immunofluorescence, immunoprecipitation, and Western blot assays. We found that HCoV-NL63 replicase products can be detected at 24 h postinfection and that these proteins accumulate in perinuclear sites, consistent with membrane-associated replication complexes. To determine which viral proteases are responsible for processing these products, we generated constructs representing the amino-terminal end of the HCoV-NL63 replicase gene and established protease cis-cleavage assays. We found that PLP1 processes cleavage site 1 to release nsp1, whereas PLP2 is responsible for processing both cleavage sites 2 and 3 to release nsp2 and nsp3. We expressed and purified PLP2 and used a peptide-based assay to identify the cleavage sites recognized by this enzyme. Furthermore, by using K48-linked hexa-ubiquitin substrate and ubiquitin-vinylsulfone inhibitor specific for deubiquitinating enzymes (DUBs), we confirmed that, like severe acute respiratory syndrome (SARS) CoV PLpro, HCoV-NL63 PLP2 has DUB activity. The identification of the replicase products and characterization of HCoV-NL63 PLP DUB activity will facilitate comparative studies of CoV proteases and aid in the development of novel antiviral reagents directed against human pathogens such as HCoV-NL63 and SARS-CoV.",,"['Chen, Zhongbin', 'Wang, Yanhua', 'Ratia, Kiira', 'Mesecar, Andrew D.', 'Wilkinson, Keith D.', 'Baker, Susan C.']",,,,
,PMC,Murine Hepatitis Virus Replicase Protein nsp10 Is a Critical Regulator of Viral RNA Synthesis,http://dx.doi.org/10.1128/JVI.02805-06,PMC1900072,,,"Coronavirus replication requires proteolytic processing of the large polyprotein encoded by ORF1a/ab into putative functional intermediates and eventually ∼15 mature proteins. The C-terminal ORF1a protein nsp10 colocalizes with viral replication complexes, but its role in transcription/replication is not well defined. To investigate the role of nsp10 in coronavirus transcription/replication, alanine replacements were engineered into a murine hepatitis virus (MHV) infectious clone in place of conserved residues in predicted functional domains or charged amino acid pairs/triplets, and rescued viruses were analyzed for mutant phenotypes. Of the 16 engineered clones, 5 viable viruses were rescued, 3 mutant viruses generated no cytopathic effect but were competent to synthesize viral subgenomic RNAs, and 8 were not viable. All viable mutants showed reductions in growth kinetics and overall viral RNA synthesis, implicating nsp10 as being a cofactor in positive- or negative-strand synthesis. Viable mutant nsp10-E2 was compromised in its ability to process the nascent polyprotein, as processing intermediates were detected in cells infected with this virus that were not detectable in wild-type infections. Mapping the mutations onto the crystal structure of severe acute respiratory syndrome virus nsp10 identified a central core resistant to mutation. Mutations targeting residues in or near either zinc-binding finger generated nonviable phenotypes, demonstrating that both domains are essential to nsp10 function and MHV replication. All mutations resulting in viable phenotypes mapped to loops outside the central core and were characterized by a global decrease in RNA synthesis. These results demonstrate that nsp10 is a critical regulator of coronavirus RNA synthesis and may play an important role in polyprotein processing.",,"['Donaldson, Eric F.', 'Sims, Amy C.', 'Graham, Rachel L.', 'Denison, Mark R.', 'Baric, Ralph S.']",,,,
,PMC,Comprehensive characterization of MHC class II haplotypes in Mauritian cynomolgus macaques,http://dx.doi.org/10.1007/s00251-007-0209-7,PMC2836927,,,"There are currently no non-human primate models with fully defined major histocompatibility complex (MHC) class II genetics. We recently showed that 6 common MHC haplotypes account for essentially all MHC diversity in cynomolgus macaques (Macaca fascicularis) from the island of Mauritius. Here we employ cDNA cloning and sequencing to comprehensively characterize full length MHC class II alleles expressed at the Mafa–DPA, -DPB, -DQA, -DQB, -DRA, and –DRB loci on the 6 common haplotypes. We describe 34 full-length MHC class II alleles, 12 of which are completely novel. Polymorphism was evident at all six loci, including DPA which is considered monomorphic in rhesus macaques. Similar to other old world monkeys, Mauritian cynomolgus macaques (MCM) share MHC class II allelic lineages with humans at the DQ and DR loci, but not at the DP loci. Additionally, we identified extensive sharing of MHC class II alleles between MCM and other non-human primates. The characterization of these full length expressed MHC class II alleles will enable researchers to generate MHC class II transferent cell lines and tetramers that can be used to explore CD4+ T-lymphocyte responses in MCM.",,"['O’Connor, Shelby L.', 'Blasky, Alex J.', 'Pendley, Chad J.', 'Becker, Ericka A.', 'Wiseman, Roger W.', 'Karl, Julie A.', 'Hughes, Austin L.', 'O’Connor, David H.']",,,,
,PMC,The magic behind stem cells,http://dx.doi.org/10.1007/s10815-007-9123-z,PMC3454971,,,"This review article summarizes historical development of stem cell research, presents current knowledge on the plasticity potential of both embryonic and adult stem cells and discusses on the future of stem cell based therapies.",,"['Zech, Nicolas H.', 'Shkumatov, Artem', 'Koestenbauer, Sonja']",,,,
,PMC,The X and Why of Xenobiotics in Primary Biliary Cirrhosis,http://dx.doi.org/10.1016/j.jaut.2007.02.003,PMC1934549,,,"Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease characterized by inflammation and destruction of intrahepatic biliary epithelial cells, ultimately leading to liver failure. The serological hallmark of PBC is the presence of high-titer antimitochondrial antibodies (AMA) against the inner lipoyl domain of E2 subunits of 2-oxo-acid dehydrogenase complexes, in particular the E2 component of the pyruvate dehydrogenase complex (PDC-E2). The initiating events triggering the autoimmune response are not yet identified but the hypothesis of molecular mimicry is a widely proposed mechanism for the development of autoimmunity in PBC. Several candidates, including bacteria and viruses have been suggested as causative agents, but also environmental factors, such as chemical xenobiotics, have been implicated in the pathogenesis of primary biliary cirrhosis. In this review, we will discuss our current knowledge of the immunoreactivity of xenobiotically modified PDC peptide antigens. In addition, we will provide a working hypothesis how xenobiotic modification of antigens might occur that ultimately leads to the breaking of self-tolerance and the induction of PBC.",,"['Rieger, Roman', 'Gershwin, M. Eric']",,,,
,PMC,Identification of Mouse Hepatitis Coronavirus A59 Nucleocapsid Protein Phosphorylation Sites,http://dx.doi.org/10.1016/j.virusres.2007.02.008,PMC2001268,,,"The coronavirus nucleocapsid (N) is a multifunctional phosphoprotein that encapsidates the genomic RNA into a helical nucleocapsid within the mature virion. The protein also plays roles in viral RNA transcription and/or replication and possibly viral mRNA translation. Phosphorylation is one of the most common post-translation modifications that plays important regulatory roles in modulating protein functions. It has been speculated for sometime that phosphorylation could play an important role in regulation of coronavirus N protein functions. As a first step toward positioning to address this we have identified the amino acids that are phosphorylated on the mouse hepatitis coronavirus (MHV) A59 N protein. High performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was used to identify phosphorylated sites on the N protein from both infected cells and purified extracellular virions. A total of six phosphorylated sites (S162, S170, T177, S389, S424 and T428) were identified on the protein from infected cells. The same six sites were also phosphorylated on the extracellular mature virion N protein. This is the first identification of phosphorylated sites for a group II coronavirus N protein.",,"['White, Tiana C.', 'Yi, Zhengping', 'Hogue, Brenda G.']",,,,
,PMC,Synergistic Roles of Antibody and Interferon in Noncytolytic Clearance of Sindbis Virus from Different Regions of the Central Nervous System,http://dx.doi.org/10.1128/JVI.01152-06,PMC1900320,,,"Sindbis virus (SINV) is an alphavirus that causes infection of neurons and encephalomyelitis in adult immunocompetent mice. Recovery can occur without apparent neurological damage. To better define the factors facilitating noncytolytic clearance of SINV in different regions of the central nervous system (CNS) and the roles of innate and adaptive immune responses at different times during infection, we have characterized SINV infection and clearance in the brain, brain stem, and spinal cords of severe combined immunodeficiency (SCID) and C57BL/6 (wild-type [WT]) mice and mice deficient in beta interferon (IFN-β) (BKO), antibody (μMT), IFN-γ (GKO), IFN-γ receptor (GRKO), and both antibody and IFN-γ (μMT/GKO). WT mice cleared infectious virus by day 8, while SCID mice had persistent virus replication at all sites. For 3 days after infection, BKO mice had higher titers at all sites than WT mice, despite similar IFN-α production, but cleared virus similarly. GKO and GRKO mice cleared infectious virus from all sites by days 8 to 10 and, like WT mice, displayed transient reactivation at 12 to 22 days. μMT mice did not clear virus from the brain, and clearance from the brain stem and lumbar spinal cord was delayed, followed by reactivation. Eighty-one days after infection, μMT/GKO mice had not cleared virus from any site, but titers were lower than for SCID mice. These studies show that IFN-β is independently important for early control of CNS virus replication, that antiviral antibody is critical for clearance from the brain, and that both antibody and IFN-γ contribute to prevention of reactivation after initial clearance.",,"['Burdeinick-Kerr, Rebeca', 'Wind, Jennifer', 'Griffin, Diane E.']",,,,
,PMC,Inhibition of Transcription of the Beta Interferon Gene by the Human Herpesvirus 6 Immediate-Early 1 Protein,http://dx.doi.org/10.1128/JVI.02443-06,PMC1900312,,,"Human herpesviruses (HHV) are stealth pathogens possessing several decoy or immune system evasion mechanisms favoring their persistence within the infected host. Of these viruses, HHV-6 is among the most successful human parasites, establishing lifelong infections in nearly 100% of individuals around the world. To better understand this host-pathogen relationship, we determined whether HHV-6 could interfere with the development of the innate antiviral response by affecting interferon (IFN) biosynthesis. Using inducible cell lines and transient transfection assays, we have identified the immediate-early 1 (IE1) protein as a potent inhibitor of IFN-β gene expression. IE1 proteins from both HHV-6 variants were capable of suppressing IFN-β gene induction. IE1 prevents IFN-β gene expression triggered by Sendai virus infection, double-stranded RNA (dsRNA) and dsDNA transfection, or the ectopic expression of IFN-β gene activators such as retinoic inducible gene I protein, mitochondrial antiviral signaling protein, TBK-1, IκB kinase ɛ (IKKɛ), and IFN regulatory factor 3 (IRF3). While the stability of IFN-β mRNA is not affected, IE1-expressing cells have reduced levels of dimerized IRF3 and nucleus-translocated IRF3 in response to activation by TBK-1 or IKKɛ. Using nuclear extracts and gel shift experiments, we could demonstrate that in the presence of IE1, IRF3 does not bind efficiently to the IFN-β promoter sequence. Overall, these results indicate that the IE1 protein of HHV-6, one of the first viral proteins synthesized upon viral entry, is a potent suppressor of IFN-β gene induction and likely contributes to favor the establishment of and successful infection of cells with this virus.",,"['Jaworska, Joanna', 'Gravel, Annie', 'Fink, Karin', 'Grandvaux, Nathalie', 'Flamand, Louis']",,,,
,PMC,UK's chief medical adviser proposes global health strategy,http://dx.doi.org/10.1136/bmj.39153.404375.4E,PMC1828300,,,,,"Mayor, Susan",,,,
,PMC,Mycobacterium tuberculosis Antigen 85A Induces Th-1 Immune Responses in Systemic Sarcoidosis,http://dx.doi.org/10.1007/s10875-007-9080-4,PMC3962023,,,"Sarcoidosis is a granulomatous disease of unknown etiology, characterized by a Th-1 immunophenotype. Although humoral immune responses by sarcoidosis subjects to mycobacterial proteins have been detected, mycobacterial antigens capable of inducing cellular immune responses in sarcoidosis subjects have not been reported. We used the enzyme-linked immunospot assay to assess for recognition of the Mycobacterium tuberculosis mycolyl transferase, Antigen 85A, by peripheral blood mononuclear cells from 25 sarcoidosis subjects, 22 PPD− (purified protein derivative) healthy volunteers, and 16 PPD+ healthy subjects. Reactivity to Ag85A whole protein was observed in 15 of 25 sarcoidosis subjects compared to 2 of 22 PPD− subjects (p = 0.0006, Fisher’s exact test) and to 14 of 16 PPD+ subjects (p = 0.084, Fisher’s exact test). Monoclonal antibody against HLA-DR inhibited recognition. In addition to immune recognition of Ag85A whole protein, peptide-mapping studies identified four immunogenic Ag85A peptides, which induced Th-1 immune responses in individual sarcoidosis subjects, suggesting that multiple epitopes from a mycobacterial protein may have a role in sarcoidosis immunopathogenesis.",,"['Hajizadeh, Rana', 'Sato, Hiroe', 'Carlisle, James', 'Nadaf, Michele T.', 'Evans, Whitney', 'Shepherd, Bryan E.', 'Miller, Robert F.', 'Kalams, Spyros A.', 'Drake, Wonder Puryear']",,,,
,PMC,Risk Factors for the Presence of High-Level Shedders of Escherichia coli O157 on Scottish Farms,http://dx.doi.org/10.1128/JCM.01690-06,PMC1865900,,,"Escherichia coli O157 infections are the cause of sporadic or epidemic cases of often bloody diarrhea that can progress to hemolytic uremic syndrome (HUS), a systematic microvascular syndrome with predominately renal and neurological complications. HUS is responsible for most deaths associated with E. coli O157 infection. From March 2002 to February 2004, approximately 13,000 fecal pat samples from 481 farms with finishing/store cattle throughout Scotland were examined for the presence of E. coli O157. A total of 441 fecal pats from 91 farms tested positive for E. coli O157. From the positive samples, a point estimate for high-level shedders was identified using mixture distribution analysis on counts of E. coli O157. Models were developed based on the confidence interval surrounding this point estimate (high-level shedder, greater than 10(3) or greater than 10(4) CFU g(−1) feces). The mean prevalence on high-level-shedding farms was higher than that on low-level-shedding farms. The presence of a high-level shedder on a farm was found to be associated with a high proportion of low-level shedding, consistent with the possibility of a higher level of transmission. Analysis of risk factors associated with the presence of a high-level shedder on a farm suggested the importance of the pathogen and individual host rather than the farm environment. The proportion of high-level shedders of phage 21/28 was higher than expected by chance. Management-related risk factors that were identified included the type of cattle (female breeding cattle) and cattle stress (movement and weaning), as opposed to environmental factors, such as water supply and feed.",,"['Chase-Topping, Margo E.', 'McKendrick, Iain J.', 'Pearce, Michael C.', 'MacDonald, Peter', 'Matthews, Louise', 'Halliday, Jo', 'Allison, Lesley', 'Fenlon, Dave', 'Low, J. Christopher', 'Gunn, George', 'Woolhouse, Mark E. J.']",,,,
,PMC,Hygiene: What and why?,http://dx.doi.org/10.1503/cmaj.061741,PMC1808522,,,,,"Nicolle, Lindsay",,,,
,PMC,Optimizing the control of disease infestations at the landscape scale,http://dx.doi.org/10.1073/pnas.0607900104,PMC1829251,,,"Using a contact-process model for the spread of crop disease over a regional scale, we examine the importance of the time scale for control with respect to the cost of the epidemic. The costs include the direct cost of treating infected sites as well as the indirect costs incurred through lost yield. We first use a mean-field approximation to derive analytical results for the optimal treatment regimes that minimize the total cost of the epidemic. We distinguish short- and long-term epidemics. and show that seasonal control (short time scale) requires extreme treatment, either treating all sites or none or switching between the two at some stage during the season. The optimal long-term strategy requires an intermediate level of control that results in near eradication of the disease. We also demonstrate the importance of incorporating economic constraints by deriving a critical relationship between the epidemiological and economic parameters that determine the qualitative nature of the optimal treatment strategy. The set of optimal strategies is summarized in a policy plot, which can be used to determine the nature of the optimal treatment regime given prior knowledge of the epidemiological and economic parameters. Finally, we test the robustness of the analytical results, derived from the mean-field approximation, on the spatially explicit contact process and demonstrate robustness to implementation errors and misestimation of crucial parameters.",,"['Forster, Graeme A.', 'Gilligan, Christopher A.']",,,,
,PMC,Heathrow doctor's case at GMC will be heard in private,http://dx.doi.org/10.1136/bmj.39146.365475.DB,PMC1819520,,,,,"Dyer, Owen",,,,
,PMC,Polish politicians argue over right to expel sick foreigners,http://dx.doi.org/10.1136/bmj.39143.574433.DB,PMC1819507,,,,,"Burgermeister, Jane",,,,
,PMC,"Mendelian Inheritance in Man and Its Online Version, OMIM",,PMC1852721,,,,,"McKusick, Victor A.",,,,
,PMC,Antiviral Effects of Antisense Morpholino Oligomers in Murine Coronavirus Infection Models,http://dx.doi.org/10.1128/JVI.02360-06,PMC1900280,,,"The recent emergence of novel pathogenic human and animal coronaviruses has highlighted the need for antiviral therapies that are effective against a spectrum of these viruses. We have used several strains of murine hepatitis virus (MHV) in cell culture and in vivo in mouse models to investigate the antiviral characteristics of peptide-conjugated antisense phosphorodiamidate morpholino oligomers (P-PMOs). Ten P-PMOs directed against various target sites in the viral genome were tested in cell culture, and one of these (5TERM), which was complementary to the 5′ terminus of the genomic RNA, was effective against six strains of MHV. Further studies were carried out with various arginine-rich peptides conjugated to the 5TERM PMO sequence in order to evaluate efficacy and toxicity and thereby select candidates for in vivo testing. In uninfected mice, prolonged P-PMO treatment did not result in weight loss or detectable histopathologic changes. 5TERM P-PMO treatment reduced viral titers in target organs and protected mice against virus-induced tissue damage. Prophylactic 5TERM P-PMO treatment decreased the amount of weight loss associated with infection under most experimental conditions. Treatment also prolonged survival in two lethal challenge models. In some cases of high-dose viral inoculation followed by delayed treatment, 5TERM P-PMO treatment was not protective and increased morbidity in the treated group, suggesting that P-PMO may cause toxic effects in diseased mice that were not apparent in the uninfected animals. However, the strong antiviral effect observed suggests that with further development, P-PMO may provide an effective therapeutic approach against a broad range of coronavirus infections.",,"['Burrer, Renaud', 'Neuman, Benjamin W.', 'Ting, Joey P. C.', 'Stein, David A.', 'Moulton, Hong M.', 'Iversen, Patrick L.', 'Kuhn, Peter', 'Buchmeier, Michael J.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Accessory Protein 6 Is a Virion-Associated Protein and Is Released from 6 Protein-Expressing Cells,http://dx.doi.org/10.1128/JVI.02307-06,PMC1900234,,,"Analysis of severe acute respiratory syndrome coronavirus (SCoV) by either sucrose gradient equilibrium centrifugation or a virus capture assay using an anti-SCoV S protein antibody demonstrated that the SCoV 6 protein, which is one of the accessory proteins of SCoV, was incorporated into virus particles. Coexpression of the SCoV S, M, E, and 6 proteins was sufficient for incorporation of the 6 protein into virus-like particles. Cells transfected with plasmid expressing the 6 protein released SCoV 6 protein; however, infected cells released SCoV 6 protein only in association with SCoV particles.",,"['Huang, Cheng', 'Peters, C. J.', 'Makino, Shinji']",,,,
,PMC,"Biologic, Antigenic, and Full-Length Genomic Characterization of a Bovine-Like Coronavirus Isolated from a Giraffe",http://dx.doi.org/10.1128/JVI.02361-06,PMC1900194,,,"Coronaviruses (CoVs) possess large RNA genomes and exist as quasispecies, which increases the possibility of adaptive mutations and interspecies transmission. Recently, CoVs were recognized as important pathogens in captive wild ruminants. This is the first report of the isolation and detailed genetic, biologic, and antigenic characterization of a bovine-like CoV from a giraffe (Giraffa camelopardalis) in a wild-animal park in the United States. CoV particles were detected by immune electron microscopy in fecal samples from three giraffes with mild-to-severe diarrhea. From one of the three giraffe samples, a CoV (GiCoV-OH3) was isolated and successfully adapted to serial passage in human rectal tumor 18 cell cultures. Hemagglutination assays, receptor-destroying enzyme activity, hemagglutination inhibition, and fluorescence focus neutralization tests revealed close biological and antigenic relationships between the GiCoV-OH3 isolate and selected respiratory and enteric bovine CoV (BCoV) strains. When orally inoculated into a BCoV-seronegative gnotobiotic calf, GiCoV-OH3 caused severe diarrhea and virus shedding within 2 to 3 days. Sequence comparisons and phylogenetic analyses were performed to assess its genetic relatedness to other CoVs. Molecular characterization confirmed that the new isolate belongs to group 2a of the mammalian CoVs and revealed closer genetic relatedness between GiCoV-OH3 and the enteric BCoVs BCoV-ENT and BCoV-DB2, whereas BCoV-Mebus was more distantly related. Detailed sequence analysis of the GiCoV-OH3 spike gene demonstrated the presence of a deletion in the variable region of the S1 subunit (from amino acid 543 to amino acid 547), which is a region associated with pathogenicity and tissue tropism for other CoVs. The point mutations identified in the structural proteins (by comparing GiCoV-OH3, BCoV-ENT, BCoV-DB2, and BCoV-Mebus) were most conserved among GiCoV-OH3, BCoV-ENT, and BCoV-DB2, whereas most of the point mutations in the nonstructural proteins were unique to GiCoV-OH3. Our results confirm the existence of a bovine-like CoV transmissible to cattle from wild ruminants, namely, giraffes, but with certain genetic properties different from those of BCoVs.",,"['Hasoksuz, Mustafa', 'Alekseev, Konstantin', 'Vlasova, Anastasia', 'Zhang, Xinsheng', 'Spiro, David', 'Halpin, Rebecca', 'Wang, Shiliang', 'Ghedin, Elodie', 'Saif, Linda J.']",,,,
,PMC,Impaired angiogenesis in aminopeptidase N-null mice,http://dx.doi.org/10.1073/pnas.0611653104,PMC1815469,,,"Aminopeptidase N (APN, CD13; EC 3.4.11.2) is a transmembrane metalloprotease with several functions, depending on the cell type and tissue environment. In tumor vasculature, APN is overexpressed in the endothelium and promotes angiogenesis. However, there have been no reports of in vivo inactivation of the APN gene to validate these findings. Here we evaluated, by targeted disruption of the APN gene, whether APN participates in blood vessel formation and function under normal conditions. Surprisingly, APN-null mice developed with no gross or histological abnormalities. Standard neurological, cardiovascular, metabolic, locomotor, and hematological studies revealed no alterations. Nonetheless, in oxygen-induced retinopathy experiments, APN-deficient mice had a marked and dose-dependent deficiency of the expected retinal neovascularization. Moreover, gelfoams embedded with growth factors failed to induce functional blood vessel formation in APN-null mice. These findings establish that APN-null mice develop normally without physiological alterations and can undergo physiological angiogenesis but show a severely impaired angiogenic response under pathological conditions. Finally, in addition to vascular biology research, APN-null mice may be useful reagents in other medical fields such as malignant, cardiovascular, immunological, or infectious diseases.",,"['Rangel, Roberto', 'Sun, Yan', 'Guzman-Rojas, Liliana', 'Ozawa, Michael G.', 'Sun, Jessica', 'Giordano, Ricardo J.', 'Van Pelt, Carolyn S.', 'Tinkey, Peggy T.', 'Behringer, Richard R.', 'Sidman, Richard L.', 'Arap, Wadih', 'Pasqualini, Renata']",,,,
,PMC,"Brugia malayi: Comparison of protective immune responses induced by Bm-alt-2 DNA, recombinant Bm-ALT-2 protein and prime-boost vaccine regimens in a jird model",http://dx.doi.org/10.1016/j.exppara.2007.02.017,PMC2763209,,,"Immunization of jirds with Bm-alt-2 elicited partial protection against challenge infection with the filarial parasite Brugia malayi. In this study, we initially compared the protective immune responses elicited following immunization with recombinant Bm-ALT-2 protein regimen and Bm-alt-2 DNA regimen. These studies showed that protein vaccination conferred approximately 75% protection compared to DNA vaccination that conferred only 57% protection. Analysis of the protective immune responses showed that the protein immunization promoted a Th2-biased response with an increase in IL-4, IL-5 and IgG1 responses, whereas, the DNA vaccine promoted a Th1-biased response with profound IFN-γ and IgG2a responses. Since protein vaccination gave better results than DNA vaccination, we then wanted to evaluate whether a prime-boost vaccination that combined DNA prime and protein boost will significantly increase the protective responses induced by the protein vaccine. Our results suggest that prime-boost vaccination had no added advantage and was comparatively less effective (64% protection) than the Bm-ALT-2 protein alone vaccination. Prime boost vaccination generated mixed Th1/Th2 responses with a slightly diminished Th2 responses compared to protein vaccination. Thus, our results suggest that Bm-ALT-2 protein vaccination regimen may be slightly better than prime-boost vaccine regimen and the mechanism of protection appears to be largely mediated by a Th2-biased response.",,"['Thirugnanam, Sivasakthivel', 'Pandiaraja, Pandurangan', 'Ramaswamy, Kalyanasundaram', 'Murugan, Vadivel', 'Gnanasekar, Munirathinam', 'Nandakumar, Krithika', 'Reddy, Maryada Venkata Rami', 'Kaliraj, Perumal']",,,,
,PMC,"Immunomodulatory Peptide from Cystatin, a Natural Cysteine Protease Inhibitor, against Leishmaniasis as a Model Macrophage Disease",http://dx.doi.org/10.1128/AAC.01555-06,PMC1855531,,,"Cystatin, a natural cysteine protease inhibitor, has strong antileishmanial activity, which is due to its potential to induce nitric oxide (NO) generation from macrophages. Cysteine protease-inhibitory activity and NO-up-regulatory activity correspond to different regions, as revealed by the dissection of cystatin cDNA into nonoverlapping fragments. By using synthetic overlapping peptides, the NO-up-regulatory activity was found to be confined to a 10-mer sequence. In addition to having reasonable inhibitory effects on amastigote multiplication within macrophages (50% inhibitory concentration, 5.2 μg/ml), 97 and 93% suppression, respectively, of liver and spleen parasite burdens was achieved with the 10-mer peptide at a dose of 0.5 mg/kg of body weight/day, given consecutively for 4 days along with a suboptimal dose of gamma interferon in a 45-day mouse model of visceral leishmaniasis. Peptide treatment modulated the levels of cytokine secretion by infected splenocytes, with increased levels of interleukin-12 and tumor necrosis factor alpha and increased inducible NO synthase production, and also resulted in resistance to reinfection. The generation of a natural peptide from cystatin with robust immunomodulatory potential may therefore provide a promising therapeutic agent for macrophage-associated diseases.",,"['Mukherjee, Snigdha', 'Ukil, Anindita', 'Das, Pijush K.']",,,,
,PMC,Caring for a Surge of Hurricane Katrina Evacuees in Primary Care Clinics,http://dx.doi.org/10.1370/afm.646,PMC1838682,,,"Primary care physicians are rarely mentioned in medical disaster plans. We describe how a group of mostly family physicians and administrators of the JPS Health Network (JPS) took primary responsibility for 3,700 evacuees of Hurricane Katrina who came to Tarrant County, Texas. JPS provided medical care to 1,664 (45%) evacuees during a 2-week period. The most common needs were medications for chronic illnesses and treatment of skin infections (primarily on the feet). The JPS Emergency Department saw only 148 evacuees, most of whom arrived by their own transportation and were not seriously ill. JPS created a triage center located several miles from the hospital that referred almost all evacuees with health care needs to a primary care clinic. It was an effective approach for caring for the medical needs of disaster victims and prevented an emergency department and hospital from being overwhelmed. The JPS experience may guide future planning efforts for natural or manmade disasters, especially pandemic threats.",,"['Edwards, Thomas D.', 'Young, Richard A.', 'Lowe, Adonna F.']",,,,
,PMC,Health is a foreign policy concern,http://dx.doi.org/10.2471/BLT.07.100307,PMC2636239,,,"Until recently, governments left health to their health ministries. But that has changed in the age of globalization, porous borders, and unprecedented levels of travel and migration. In this interview, Norwegian Foreign Minister Jonas Gahr Støre argues that health should be a major consideration for economic and foreign policy-makers. Next month Støre and six other foreign ministers plan to release a report on how foreign policy-makers can and should address health issues.",,,,,,
,PMC,Health imperatives in foreign policy: the case of Malaysia,http://dx.doi.org/10.2471/BLT.06.037119,PMC2636238,,,"Malaysia’s global, regional and bilateral international health relations are surveyed against the historical backdrop of the country’s foreign policy. Malaysia has always participated in multilateral agencies, most notably the World Health Organization, as such agencies are part of the longstanding fabric of “good international citizenship”. The threats of infectious diseases to human health and economic activity have caused an intensification and an organizational formalization of Malaysian health diplomacy, both regionally and bilaterally. Such diplomacy has also established a basis for developing a wider set of cooperative relationships that go beyond responding to the threat of pandemics. As Malaysia approaches “developed” status, its health sector is becoming increasingly integrated into the global economy through joint research and development ventures and transnational investment. At the same time, it will have the technological, financial and human resources to play an expanded altruistic role in global and regional health.",,"['Barraclough, Simon', 'Phua, Kai-Lit']",,,,
,PMC,"Making G8 leaders deliver: an analysis of compliance and health commitments, 1996–2006",http://dx.doi.org/10.2471/BLT.06.039917,PMC2636233,,,"International health policy-makers now have a variety of institutional instruments with which to pursue their global and national health goals. These instruments range from the established formal multilateral organizations of the United Nations to the newer restricted-membership institutions of the Group of Eight (G8). To decide where best to deploy scarce resources, we must systematically examine the G8’s contributions to global health governance. This assessment explores the contributions made by multilateral institutions such as the World Health Organization, and whether Member States comply with their commitments. We assessed whether G8 health governance assists its member governments in managing domestic politics and policy, in defining dominant normative directions, in developing and complying with collective commitments and in developing new G8-centred institutions. We found that the G8’s performance improved substantially during the past decade. The G8 Member States function equally well, and each is able to combat diseases. Compliance varied among G8 Member States with respect to their health commitments, and there is scope for improvement. G8 leaders should better define their health commitments and set a one-year deadline for their delivery. In addition, Member States must seek WHO’s support and set up an institution for G8 health ministers.",,"['Kirton, John J', 'Roudev, Nikolai', 'Sunderland, Laura']",,,,
,PMC,Health and security in foreign policy,http://dx.doi.org/10.2471/BLT.06.036889,PMC2636232,,,,,"['Katz, Rebecca', 'Singer, Daniel A']",,,,
,PMC,The value of a human rights perspective in health and foreign policy,http://dx.doi.org/10.2471/BLT.07.040287,PMC2636231,,,,,"Robinson, Mary",,,,
,PMC,Health and foreign policy: influences of migration and population mobility,http://dx.doi.org/10.2471/BLT.06.036962,PMC2636223,,,"International interest in the relationship between globalization and health is growing, and this relationship is increasingly figuring in foreign policy discussions. Although many globalizing processes are known to affect health, migration stands out as an integral part of globalization, and links between migration and health are well documented. Numerous historical interconnections exist between population mobility and global public health, but since the 1990s new attention to emerging and re-emerging infectious diseases has promoted discussion of this topic. The containment of global disease threats is a major concern, and significant international efforts have received funding to fight infectious diseases such as malaria, tuberculosis and HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome). Migration and population mobility play a role in each of these public health challenges. The growing interest in population mobility’s health-related influences is giving rise to new foreign policy initiatives to address the international determinants of health within the context of migration. As a result, meeting health challenges through international cooperation and collaboration has now become an important foreign policy component in many countries. However, although some national and regional projects address health and migration, an integrated and globally focused approach is lacking. As migration and population mobility are increasingly important determinants of health, these issues will require greater policy attention at the multilateral level.",,"['MacPherson, Douglas W', 'Gushulak, Brian D', 'Macdonald, Liane']",,,,
,PMC,Bridging health and foreign policy: the role of health impact assessments,http://dx.doi.org/10.2471/BLT.06.037077,PMC2636222,,,"Health impact assessment (HIA) is an important tool for exploring the intersection between health and foreign policy, offering a useful analytical approach to increase positive health impacts and minimize negative impacts. Numerous subject areas have brought health and foreign policy together. Yet further opportunities exist for HIA to address a broader range of health impacts that otherwise may not be seen as relevant to foreign policy. HIA may also improve the quality of scientific evidence available to policy-makers. The Framework Convention on Tobacco Control offers lessons for the strategic use of HIA. However, HIA alone is limited in influencing these decision-making processes, notably when issues diverge from other core concerns such as economics and security. In such cases, HIA is an important tool to be used alongside the mobilization of key constituencies and public support.",,"['Lee, Kelley', 'Ingram, Alan', 'Lock, Karen', 'McInnes, Colin']",,,,
,PMC,COLD-fX,,PMC1949084,,,,,"['Nguyen, Anne', 'Slavik, Victoria']",,,,
,PMC,News from the AMMI-CACMID Annual Meeting,,PMC2533536,,,,,,,,,
,PMC,Risk of transmission of airborne infection during train commute based on mathematical model,http://dx.doi.org/10.1007/BF02898153,PMC2723643,,,"OBJECTIVE: In metropolitan areas in Japan, train commute is very popular that trains are over-crowded with passengers during rush hour. The purpose of this study is to quantify public health risk related to the inhalation of airborne infectious agents in public vehicles during transportation based on a mathematical model. METHODS: The reproduction number for the influenza infection in a train (R(A)) was estimated using a model based on the Wells-Riley model. To estimate the influence of environmental parameters, the duration of exposure and the number of passengers were varied. If an infected person will not use a mask and all susceptible people will wear a mask, a reduction in the risk of transmission could be expected. RESULTS: The estimated probability distribution of R(A) had a median of 2.22, and the distribution was fitted to a log-normal distribution with a geometric mean of 2.22 and a geometric standard deviation of 1.53, under the condition that there are 150 passengers, and that 13 ventilation cycles per hour, as required by law, are made. If the exposure time is less than 30 min, the risk may be low. The exposure time can increase the risk linearly. The number of passengers also increases the risk. However, R(A) is fairly insensitive to the number of passengers. Surgical masks are somewhat effective, whereas High-Efficiency Particulate Air (HEPA) masks are quite effective. Doubling the rate of ventilation reduces R(A) to almost 1. CONCLUSIONS: Because it is not feasible for all passengers to wear a HEPA mask, and improvement in the ventilation seems to be an effective and feasible means of preventing influenza infection in public trains.",,"Furuya, Hiroyuki",,,,
,PMC,Role for Nonstructural Protein 1 of Severe Acute Respiratory Syndrome Coronavirus in Chemokine Dysregulation,http://dx.doi.org/10.1128/JVI.02744-06,PMC1865949,,,,,"['Law, Anna H. Y.', 'Lee, Davy C. W.', 'Cheung, Benny K. W.', 'Yim, Howard C. H.', 'Lau, Allan S. Y.']",,,,
,PMC,Life sciences and biotechnology in China,http://dx.doi.org/10.1098/rstb.2007.2025,PMC2435562,,,"Life science and biotechnology have become a top priority in research and development in many countries as the world marches into the new century. China as a developing country with a 1.3 billion population and booming economy is actively meeting the challenge of a new era in this area of research. Owing to support from the government and the scientific community, and reform to improve the infrastructure, recent years have witnessed a rapid progress in some important fields of life science and biotechnology in China, such as genomics and protein sciences, neuroscience, systematics, super-hybrid rice research, stem cell and cloning technology, gene therapy and drug/vaccine development. The planned expansion and development of innovation in related sectors and the area of bioethics are described and discussed.",,"['Chen, Zhu', 'Wang, Hong-Guang', 'Wen, Zhao-Jun', 'Wang, Yihuang']",,,,
,PMC,Importance of the Penultimate Positive Charge in Mouse Hepatitis Coronavirus A59 Membrane Protein,http://dx.doi.org/10.1128/JVI.02427-06,PMC1900233,,,"The coronavirus membrane (M) protein carboxy tail interacts with the nucleocapsid during virus assembly. Previous studies demonstrated that the two terminal residues are important, and the charged residue (R227) in the penultimate position in the mouse hepatitis coronavirus (MHV) A59 M protein was suggested to participate in intermolecular interactions with negative charges in the nucleocapsid (N) protein. To determine the significance of the positive charge at position 227, we substituted the arginine with lysine (K), aspartic acid (D), glutamic acid (E), or alanine (A) and studied these by reverse genetics in the context of a MHV full-length infectious clone. Viruses with wild-type phenotype were readily recovered with the K or A substitutions. In contrast, negative-charge substitutions were not tolerated as well. In all recovered R227D viruses the negative charge was replaced with heterologous residues resulting from apparent template switching during negative-strand synthesis of subgenomic RNA 7. An additional second-site compensatory V202I substitution was present in some viruses. Recovered R227E viruses had second-site changes within the M protein carboxy tail that were partially compensatory. Significantly, most of the second site changes in the R227E mutant viruses were previously shown to compensate for the removal of negative charges in the N protein. Our results strongly indicate that a positive charge is not absolutely required. It is clear that other regions within the tail must also be involved in helping mediate interactions between the M protein and the nucleocapsid.",,"['Verma, Sandhya', 'Lopez, Lisa A.', 'Bednar, Valerie', 'Hogue, Brenda G.']",,,,
,PMC,Connection and communication vital to handling a pandemic in Ontario,http://dx.doi.org/10.1503/cmaj.070184,PMC1800334,,,,,"Silversides, Ann",,,,
,PMC,SARS molecular epidemiology: a Chinese fairy tale of controlling an emerging zoonotic disease in the genomics era,http://dx.doi.org/10.1098/rstb.2007.2034,PMC2435571,,,"Severe acute respiratory syndrome (SARS) was the first natural disaster that challenged the Chinese people at the beginning of the twenty-first century. It was caused by a novel animal coronavirus, never recognized or characterized before. This SARS coronavirus (SARS-CoV) exploited opportunities provided by ‘wet markets’ in southern China to adapt to the palm civet and human. Under the positive selection pressure of human host, certain mutated lineages of the virus became readily transmissible between humans and thus caused the epidemic of 2002–2003. This review will provide first-hand information, particularly from Guangdong, China, about the initial epidemiology, the identification of the aetiological agent of the disease, the molecular evolution study of the virus, the finding of SARS-like CoV in horseshoe bats and the mechanistic analysis for the cross-host tropism transition. The substantial scientific contributions made by the Chinese scientists towards understanding the virus and the disease will be emphasized. Along with the description of the scientific discoveries and analyses, the significant impact of these researches upon the public health measurement or regulations will be highlighted. It is aimed to appreciate the concerted and coordinated global response that controlled SARS within a short period of time as well as the research strategy and methodology developed along with this process, which can be applied in response to other public health challenges, particularly the future emerging/re-merging infectious diseases.",,"Zhao, Guo-ping",,,,
,PMC,History of protein crystallography in China,http://dx.doi.org/10.1098/rstb.2007.2032,PMC2435569,,,"China has a strong background in X-ray crystallography dating back to the 1920s. Protein crystallography research in China was first developed following the successful synthesis of insulin in China in 1966. The subsequent determination of the three-dimensional structure of porcine insulin made China one of the few countries which could determine macromolecular structures by X-ray diffraction methods in the late 1960s and early 1970s. After a slow period during the 1970s and 1980s, protein crystallography in China has reached a new climax with a number of outstanding accomplishments. Here, I review the history and progress of protein crystallography in China and detail some of the recent research highlights, including the crystal structures of two membrane proteins as well as the structural genomics initiative in China.",,"Rao, Zihe",,,,
,PMC,Novel Microneutralization Assay for HCMV Using Automated Data Collection and Analysis,http://dx.doi.org/10.1016/j.jim.2007.02.001,PMC1933494,,,"In addition to being sensitive and specific, an assay for the assessment of neutralizing antibody activity from clinical trial samples must be amenable to automation for use in high-volume screening. To that effect, we developed a 96-well microplate assay for the measurement of HCMV-neutralizing activity in human sera using the HCMV-permissive human cell line HEL-299 and the laboratory strain of HCMV AD169. The degree to which neutralizing antibodies diminish HCMV infection of cells in the assay is determined by quantifying the nuclei of infected cells based on expression of the 72 kDa IE1 viral protein. Nuclear IE1 is visualized using a highly sensitive immunoperoxidase staining and the stained nuclei are counted using an automated ELISPOT analyzer. The use of Half Area 96-well microplates, with wells in which the surface area of the well bottom is half the area of a standard 96-well microplate plate, improves signal detection compared with standard microplates and economizes on the usage of indicator cells, virus, and reagents. The staining process was also streamlined by using a microplate washer and data analysis was simplified and accelerated by employing a software program that automatically plots neutralization curves and determines NT(50) values using 4-PL curve fitting. The optimized assay is not only fast and convenient, but also specific, sensitive, precise and reproducible and thus has the characteristics necessary for use in measuring HCMV neutralizing activity in the sera of vaccine trial subjects such as the recipients of Vical’s HCMV pDNA vaccine candidates.",,"['Abai, Anna Maria', 'Smith, Larry R.', 'Wloch, Mary K.']",,,,
,PMC,Interferon-γ-Oligodendrocyte Interactions in the Regulation of Experimental Autoimmune Encephalomyelitis,http://dx.doi.org/10.1523/JNEUROSCI.4689-06.2007,PMC6673565,,,"Experimental autoimmune encephalomyelitis (EAE) is an animal model of the human demyelinating disorder multiple sclerosis (MS). The immune cytokine interferon-gamma (IFN-γ) is believed to participate in disease pathogenesis in both EAE and MS. In the present study, we examined the significance of IFN-γ-oligodendrocyte interactions in the course of EAE. For the purpose of our study, we used the previously described [proteolipid protein/suppressor of cytokine signaling 1 (PLP/SOCS1)] transgenic mouse line that displays suppressed oligodendrocyte responsiveness to IFN-γ. PLP/SOCS1 mice developed EAE with an accelerated onset associated with enhanced early inflammation and markedly increased oligodendrocyte apoptosis. Moreover, we found that IFN-γ pretreatment of mature oligodendrocytes in vitro had a protective effect against oxidative stress and the inhibition of proteasome activity and resulted in upregulation in expression of a number of chemokines, including CXCL10 (IP10), CCL2 (MCP-1), CCL3 (MCP-1α), and CCL5 (RANTES). These results suggest that IFN-γ-oligodendrocyte interactions are of significance to the clinical and pathological aspects of EAE. In addition, the present study suggests that oligodendrocytes are not simply targets of inflammatory injury but active participants of the neuroimmune network operating during the course of EAE.",,"['Balabanov, Roumen', 'Strand, Krystle', 'Goswami, Rajendra', 'McMahon, Eileen', 'Begolka, Wendy', 'Miller, Stephen D.', 'Popko, Brian']",,,,
,PMC,Natural Mutations in the Receptor Binding Domain of Spike Glycoprotein Determine the Reactivity of Cross-Neutralization between Palm Civet Coronavirus and Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.02389-06,PMC1900161,,,"The severe acute respiratory syndrome (SARS) outbreak of 2002 and 2003 occurred as a result of zoonotic transmission. Coronavirus (CoV) found in naturally infected palm civet (civet-CoV) represents the closest genetic relative to SARS-CoV, but the degree and the determinants of cross-neutralization among these viruses remain to be investigated. Studies indicate that the receptor binding domain (RBD) of the SARS-CoV spike (S) glycoprotein contains major determinants for viral entry and neutralization. We aim to characterize the impact of natural mutations within the RBDs of civet-CoVs on viral entry and cross-neutralization. In this study, the S glycoprotein genes were recovered from naturally infected civets in central China (Hubei province), extending the geographic distribution of civet-CoV beyond the southeastern province of Guangdong. Moreover, pseudoviruses generated in our laboratory with four civet S genes, each with a distinct RBD, infected cells expressing human receptor angiotensin-converting enzyme 2, but with 90 to 95% less efficiency compared to that of SARS-CoV. These four civet S genes were also constructed as DNA vaccines to immunize mice. Immunized sera elicited against most civet S glycoproteins displayed potent neutralizing activities against autologous viruses but were much less efficient (50% inhibitory concentration, 20- to 40-fold) at neutralizing SARS-CoV and vice versa. Convalescence-phase sera from humans were similarly ineffective against the dominant civet pseudovirus. Our findings suggest that the design of SARS vaccine should consider not only preventing the reemergence of SARS-CoV but also providing cross-protection, thus interrupting zoonotic transmission of a group of genetically divergent civet CoVs of broad geographic origin.",,"['Liu, Li', 'Fang, Qing', 'Deng, Fei', 'Wang, Hanzhong', 'Yi, Christopher E.', 'Ba, Lei', 'Yu, Wenjie', 'Lin, Richard D.', 'Li, Taisheng', 'Hu, Zhihong', 'Ho, David D.', 'Zhang, Linqi', 'Chen, Zhiwei']",,,,
,PMC,Temporal relationship between air pollutants and hospital admissions for chronic obstructive pulmonary disease in Hong Kong,http://dx.doi.org/10.1136/thx.2006.076166,PMC2117326,,,"AIMS: To assess any relationship between the levels of ambient air pollutants and hospital admissions for chronic obstructive pulmonary disease (COPD) in Hong Kong. METHODS: A retrospective ecological study was undertaken. Data of daily emergency hospital admissions to 15 major hospitals in Hong Kong for COPD and indices of air pollutants (sulphur dioxide (SO(2)), nitrogen dioxide (NO(2)), ozone (O(3)), particulates with an aerodynamic diameter of <10 μm (PM(10)) and 2.5 μm (PM(2.5))) and meteorological variables from January 2000 to December 2004 were obtained from several government departments. Analysis was performed using generalised additive models with Poisson distribution, adjusted for the effects of time trend, season, other cyclical factors, temperature and humidity. Autocorrelation and overdispersion were corrected. RESULTS: Significant associations were found between hospital admissions for COPD with all five air pollutants. Relative risks for admission for every 10 μg/m(3) increase in SO(2), NO(2), O(3), PM(10) and PM(2.5) were 1.007, 1.026, 1.034, 1.024 and 1.031, respectively, at a lag day ranging from lag 0 to cumulative lag 0–5. In a multipollutant model, O(3), SO(2) and PM(2.5) were significantly associated with increased admissions for COPD. SO(2), NO(2) and O(3) had a greater effect on COPD admissions in the cold season (December to March) than during the warm season. CONCLUSION: Ambient concentrations of air pollutants have an adverse effect on hospital admissions for COPD in Hong Kong, especially during the winter season. This might be due to indoor exposure to outdoor pollution through open windows as central heating is not required in the mild winter. Measures to improve air quality are urgently needed.",,"['Ko, Fanny W S', 'Tam, Wilson', 'Wong, Tze Wai', 'Chan, Doris P S', 'Tung, Alvin H', 'Lai, Christopher K W', 'Hui, David S C']",,,,
,PMC,Structural definition of a conserved neutralization epitope on HIV-1 gp120,http://dx.doi.org/10.1038/nature05580,PMC2584968,,,"The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 Å resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally invariant surface that overlaps a distinct subset of the CD4-binding site. This surface is involved in the metastable attachment of CD4, before the gp120 rearrangement required for stable engagement. A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1.",,"['Zhou, Tongqing', 'Xu, Ling', 'Dey, Barna', 'Hessell, Ann J.', 'Van Ryk, Donald', 'Xiang, Shi-Hua', 'Yang, Xinzhen', 'Zhang, Mei-Yun', 'Zwick, Michael B.', 'Arthos, James', 'Burton, Dennis R.', 'Dimitrov, Dimiter S.', 'Sodroski, Joseph', 'Wyatt, Richard', 'Nabel, Gary J.', 'Kwong, Peter D.']",,,,
,PMC,"Participation of Rab5, an Early Endosome Protein, in Hepatitis C Virus RNA Replication Machinery",http://dx.doi.org/10.1128/JVI.01366-06,PMC1900164,,,"Like most positive-strand RNA viruses, hepatitis C virus (HCV) is believed to replicate its genome on the surface of rearranged membranes. We have shown previously that HCV NS4AB, but not the product NS4B, inhibits endoplasmic reticulum (ER)-to-Golgi protein traffic (K. V. Konan, T. H. Giddings, Jr., M. Ikeda, K. Li, S. M. Lemon, and K. Kirkegaard, J. Virol. 77:7843-7855). However, both NS4AB and NS4B can induce “membranous web” formation, first reported by Egger et al. (D. B Egger, R. Gosert, L. Bianchi, H. E. Blum, D. Moradpour, and K. Bienz, J. Virol. 76:5974-5984), which is also observed in HCV-infected cells (Y. Rouille, F. Helle, D. Delgrange, P. Roingeard, C. Voisset, E. Blanchard, S. Belouzard, J. McKeating, A. H. Patel, G. Maertens, T. Wakita, C. Wychowski, and J. Dubuisson, J. Virol. 80:2832-2841) and cells that bear a subgenomic NS5A-green fluorescent protein (GFP) replicon (D. Moradpour, M. J. Evans, R. Gosert, Z. Yuan, H. E. Blum, S. P. Goff, B. D. Lindenbach, and C. M. Rice, J. Virol. 78:7400-7409). To determine the intracellular origin of the web, we examined NS4B colocalization with endogenous cellular markers in the context of the full-length or subgenomic replicon. We found that, in addition to ER markers, early endosome (EE) proteins, including Rab5, were associated with web-inducing protein NS4B. Furthermore, an immunoisolated fraction containing NS4B was found to contain both ER and EE proteins. Using fluorescence microscopy, we showed that wild-type and constitutively active Rab5 proteins were associated with NS4B. Interestingly, expression of dominant-negative Rab5 resulted in significant loss of GFP fluorescence in NS5A-GFP replicon cells. We also found that a small reduction in Rab5 protein expression decreased HCV RNA synthesis significantly. Furthermore, transfection of labeled Rab5 small interfering RNAs into NS5A-GFP replicon cells resulted in a significant decrease in GFP fluorescence. Finally, Rab5 protein was found to coimmunoprecipitate with HCV NS4B. These studies suggest that EE proteins, including Rab5, may play a role in HCV genome replication or web formation.",,"['Stone, Michelle', 'Jia, Shuaizheng', 'Heo, Won Do', 'Meyer, Tobias', 'Konan, Kouacou V.']",,,,
,PMC,Adenovirus-Platelet Interaction in Blood Causes Virus Sequestration to the Reticuloendothelial System of the Liver,http://dx.doi.org/10.1128/JVI.02819-06,PMC1900148,,,"Intravenous (i.v.) delivery of recombinant adenovirus serotype 5 (Ad5) vectors for gene therapy is hindered by safety and efficacy problems. We have discovered a new pathway involved in unspecific Ad5 sequestration and degradation. After i.v. administration, Ad5 rapidly binds to circulating platelets, which causes their activation/aggregation and subsequent entrapment in liver sinusoids. Virus-platelet aggregates are taken up by Kupffer cells and degraded. Ad sequestration in organs can be reduced by platelet depletion prior to vector injection. Identification of this new sequestration mechanism and construction of vectors that avoid it could improve levels of target cell transduction at lower vector doses.",,"['Stone, Daniel', 'Liu, Ying', 'Shayakhmetov, Dmitry', 'Li, Zong-Yi', 'Ni, Shaoheng', 'Lieber, André']",,,,
,PMC,Xenopus Xp54 and Human RCK/p54 Helicases Functionally Replace Yeast Dhh1p in Brome Mosaic Virus RNA Replication,http://dx.doi.org/10.1128/JVI.02246-06,PMC1866127,,,"By using a Brome mosaic virus (BMV)-Saccharomyces cerevisiae system, we previously showed that the cellular Lsm1p-7p/Pat1p/Dhh1p decapping-activator complex functions in BMV RNA translation and replication. As a first approach in investigating whether the corresponding human homologues play a similar role, we expressed human Lsm1p (hLsm1p) and RCK/p54 in yeast. Expression of RCK/p54 but not hLsm1p restored the defect in BMV RNA translation and replication observed in the dhh1Δ and lsm1Δ strains, respectively. This functional conservation, together with the common replication strategies of positive-stranded RNA viruses, suggests that RCK/p54 may also play a role in the replication of positive-stranded RNA viruses that infect humans.",,"['Alves-Rodrigues, Isabel', 'Mas, Antonio', 'Díez, Juana']",,,,
,PMC,Post-SARS: more protection needed for health care workers,http://dx.doi.org/10.1503/cmaj.070096,PMC1800577,,,,,"Silversides, Ann",,,,
,PMC,Evidence for interstate transmission and increase in prevalence of bovine group B rotavirus strains with a novel VP7 genotype among diarrhoeic calves in Eastern and Northern states of India,http://dx.doi.org/10.1017/S0950268806007813,PMC2870693,,,"During a surveillance study (2003–2005) in a cattle market in Kolkata city, state of West Bengal, Eastern India, 34 (13·0%) of 260 calves with diarrhoea were positive for group B rotaviruses (GBR) by RNA electrophoresis in polyacrylamide gels. Analysis of the partial VP7 gene sequence of 28 of the 34 GBR strains revealed maximum identities (97·7–99·5% at nucleotide level and 97·8–100% at amino-acid level) with the novel bovine GBR ‘Kolkata strains’ reported in an earlier surveillance study (1·5%, n=192, 2001–2002) from the same cattle market, and shared low identities of 73·7–78·9% and 80·8–89·6%; 62·6–66·2% and 59·8–65·4%; 58·9–62·2% and 48·6–54·9% at nucleotide and amino-acid level with other bovine, human, and murine GBR. The GBR-infected calves were traced to districts in neighbouring states of West Bengal. Therefore, the present study reports a rapid increase in prevalence (13·0% in 2003–2005 against 1·5% in 2001–2002) of novel GBR strains among calves with diarrhoea, and provides evidence for interstate transmission of GBR.",,"['GHOSH, S.', 'VARGHESE, V.', 'SINHA, M.', 'KOBAYASHI, N.', 'NAIK, T.\xa0N.']",,,,
,PMC,US expert warns interdependence of countries makes world more vulnerable to flu pandemic,http://dx.doi.org/10.1136/bmj.39118.367523.DB,PMC1796705,,,,,"Roehr, Bob",,,,
,PMC,The impact of contact structure on infectious disease control: influenza and antiviral agents,http://dx.doi.org/10.1017/S0950268807007959,PMC2870680,,,"Planning adequate public health responses against emerging infectious diseases requires predictive tools to evaluate the impact of candidate intervention strategies. With current interest in pandemic influenza very high, modelling approaches have suggested antiviral treatment combined with targeted prophylaxis as an effective first-line intervention against an emerging influenza pandemic. To investigate how the effectiveness of such interventions depends on contact structure, we simulate the effects in networks with variable degree distributions. The infection attack rate can increase if the number of contacts per person is heterogeneous, implying the existence of high-degree individuals who are potential super-spreaders. The effectiveness of a socially targeted intervention suffers from heterogeneous contact patterns and depends on whether infection is predominantly transmitted to close or casual contacts. Our findings imply that the various contact networks' degree distributions as well as the allocation of contagiousness between close and casual contacts should be examined to identify appropriate strategies of disease control measures.",,"['DUERR, H.-P.', 'SCHWEHM, M.', 'LEARY, C.\xa0C.', 'De Vlas, S.\xa0J.', 'EICHNER, M.']",,,,
,PMC,Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses,http://dx.doi.org/10.1038/nature05539,PMC3197705,,,"At least five arenaviruses cause viral haemorrhagic fevers in humans. Lassa virus, an Old World arenavirus, uses the cellular receptor α-dystroglycan to infect cells(1). Machupo, Guanarito, Junin and Sabia viruses are New World haemorrhagic fever viruses that do not use α-dystroglycan(2). Here we show a specific, high-affinity association between transferrin receptor 1 (TfR1) and the entry glycoprotein (GP) of Machupo virus. Expression of human TfR1, but not human transferrin receptor 2, in hamster cell lines markedly enhanced the infection of viruses pseudotyped with the GP of Machupo, Guanarito and Junin viruses, but not with those of Lassa or lymphocytic choriomeningitis viruses. An anti-TfR1 antibody efficiently inhibited the replication of Machupo, Guanarito, Junin and Sabia viruses, but not that of Lassa virus. Iron depletion of culture medium enhanced, and iron supplementation decreased, the efficiency of infection by Junin and Machupo but not Lassa pseudoviruses. These data indicate that TfR1 is a cellular receptor for New World haemorrhagic fever arenaviruses.",,"['Radoshitzky, Sheli R.', 'Abraham, Jonathan', 'Spiropoulou, Christina F.', 'Kuhn, Jens H.', 'Nguyen, Dan', 'Li, Wenhui', 'Nagel, Jane', 'Schmidt, Paul J.', 'Nunberg, Jack H.', 'Andrews, Nancy C.', 'Farzan, Michael', 'Choe, Hyeryun']",,,,
,PMC,Early Cytokine mRNA Expression Profiles Predict Morbillivirus Disease Outcome in Ferrets,http://dx.doi.org/10.1016/j.virol.2007.01.002,PMC2697062,,,"Severe immunosuppression is a hallmark of Morbillivirus infections. To study the underlying mechanisms, we have developed a ferret model of canine distemper virus infection. The model reproduces all clinical signs of measles, but the lack of ferret-specific reagents has limited the characterization of the cellular immune response. Towards this, we cloned ferret cytokines and established semi-quantitative real-time PCR assays. To demonstrate the utility of these assays we compared the cytokine profiles elicited by lethal and non-lethal strains during the prodromal phase. We observed a general lack of cytokine induction in animals that later succumbed to the disease, whereas survivors mounted a robust and sustained response. The newly developed cytokine assays strengthen and expand the ferret model not only for Morbillivirus pathogenesis studies but also for several other human respiratory viruses including influenza and SARS.",,"['Svitek, Nicholas', 'von Messling, Veronika']",,,,
,PMC,Doctors disagree over detention of patients with extensively drug resistant tuberculosis,http://dx.doi.org/10.1136/bmj.39108.568368.DB,PMC1790784,,,,,"Moszynski, Peter",,,,
,PMC,Attenuated Measles Virus as a Vaccine Vector,http://dx.doi.org/10.1016/j.vaccine.2007.01.064,PMC3707277,,,"Live attenuated measles virus (MV) vaccines have an impressive record of safety, efficacy and ability to induce life-long immunity against measles infection. Using reverse genetics technology, such negative-strand RNA viruses can now be rescued from cloned DNA. This technology allows the insertion of exogenous genes encoding foreign antigens into the MV genome in such a way that they can be expressed by the MV vaccine strain, without affecting virus structure, propagation and cell targeting. Recombinant viruses rescued from cloned cDNA induce immune responses against both measles virus and the cloned antigens. The tolerability of MV to gene(s) insertion makes it an attractive flexible vector system, especially if broad immune responses are required. The fact that measles replication strictly occurs in the cytoplasm of infected cells without DNA intermediate has important biosafety implications and adds to the attractiveness of MV as a vector. In this article we report the characteristics of reporter gene expression (GFP, LacZ and CAT) and the biochemical, biophysical and immunological properties of recombinant MV expressing heterologous antigens of simian immunogeficiency virus (SIV).",,"['Zuniga, Armando', 'Wang, ZiLi', 'Liniger, Matthias', 'Hangartner, Lars', 'Caballero, Michael', 'Pavlovic, Jovan', 'Wild, Peter', 'Viret, Jean Francois', 'Glueck, Reinhard', 'Billeter, Martin A.', 'Naim, Hussein Y.']",,,,
,PMC,Molecular Pathology in the Lungs of Severe Acute Respiratory Syndrome Patients,http://dx.doi.org/10.2353/ajpath.2007.060469,PMC1851867,,,"Severe acute respiratory syndrome (SARS) is a novel infectious disease with disastrous clinical consequences, in which the lungs are the major target organs. Previous studies have described the general pathology in the lungs of SARS patients and have identified some of the cell types infected by SARS coronavirus (SARS-CoV). However, at the time of this writing, there were no comprehensive reports of the cellular distribution of the virus in lung tissue. In this study, we have performed double labeling combining in situ hybridization with immunohistochemistry and alternating each of these techniques separately in consecutive sections to evaluate the viral distribution on various cell types in the lungs of seven patients affected with SARS. We found that SARS-CoV was present in bronchial epithelium, type I and II pneumocytes, T lymphocytes, and macrophages/monocytes. For pneumocytes, T lymphocytes, and macrophages, the infection rates were calculated. In addition, our present study is the first to demonstrate infection of endothelial cells and fibroblasts in SARS.",,"['Ye, Juxiang', 'Zhang, Bo', 'Xu, Jian', 'Chang, Qing', 'McNutt, Michael A.', 'Korteweg, Christine', 'Gong, Encong', 'Gu, Jiang']",,,,
,PMC,Anti-Viral T-Cell Immunity + Anti-CNS Autoantibody = A Model for Human Acute Disseminated Encephalomyelitis or Multiple Sclerosis Relapse?,http://dx.doi.org/10.2353/ajpath.2007.061098,PMC1851860,,,,,"Sobel, Raymond A.",,,,
,PMC,Exacerbated Pathology of Viral Encephalitis in Mice with Central Nervous System-Specific Autoantibodies,http://dx.doi.org/10.2353/ajpath.2007.060893,PMC1851853,,,"We examine here the outcome of viral encephalomyelitis [mouse hepatitis virus (MHV) A59, Theiler’s encephalomyelitis virus, and Coxsackievirus B3] in mice with autoantibodies to a central nervous system (CNS)-specific antigen, myelin oligodendrocyte glycoprotein, that usually develop no clinical disease. Morbidity and mortality of the acute viral CNS disease was augmented by the presence of the autoantibodies in all three viral infections. Transfer of serum containing the autoantibodies at the time of infection with MHV was sufficient to reproduce the exacerbated disease. The presence of the autoantibodies was found to result in increased infiltration of mononuclear cells into the brain. Early demyelination was severely augmented in brains and spinal cords of MHV-infected mice with CNS-specific autoantibodies. The antibody-mediated exacerbation was shown to be independent of the complement system but to require expression of Fc receptors, because it was observed in C′-3-deficient but not in Fc receptor-deficient mice. Our study illustrates the possibility that infections can lead to much more profound immunopathology in the presence of an otherwise latent autoimmune condition.",,"['Burrer, Renaud', 'Buchmeier, Michael J.', 'Wolfe, Tom', 'Ting, Joey P.C.', 'Feuer, Ralph', 'Iglesias, Antonio', 'von Herrath, Matthias G.']",,,,
,PMC,"Progress in Anti-SARS Coronavirus Chemistry, Biology and Chemotherapy",http://dx.doi.org/10.1016/S0065-7743(06)41011-3,PMC2718771,,,,,"['Ghosh, Arun K.', 'Xi, Kai', 'Johnson, Michael E.', 'Baker, Susan C.', 'Mesecar, Andrew D.']",,,,
,PMC,CD154 Blockade and Donor-Specific Transfusions in DLA-Identical Marrow Transplantation in Dogs Conditioned with 1 Gy Total Body Irradiation,http://dx.doi.org/10.1016/j.bbmt.2006.10.031,PMC1831459,,,"Stable mixed donor/host chimerism has been reliably established in dogs given a sublethal dose of 2 Gy total body irradiation (TBI) before and immunosuppression with mycophenolate mofetil (MMF) or rapamycin combined with cyclosporine (CSP) after marrow transplantation from DLA-identical littermates (HCT). When TBI was reduced to 1 Gy, only transient engraftment was observed. Here we asked whether stable engraftment after 1 Gy TBI could be accomplished by reducing host vs. donor immune responsiveness through preceding CD154 blockade and infusion of donor peripheral blood mononuclear cells (PBMC). The anti-human CD154 antibody, 5c8, cross-reacted with canine lymphocytes and blocked allo-immune responses in vitro. Based on pharmacokinetic studies, six dogs received a single i.v. injection of 5 mg/kg anti-CD154 antibody (day -5) followed one day later by donor PBMC. On day 0, dogs were given 1 Gy TBI and DLA-identical marrow grafts. Postgrafting immunosuppression consisted of MMF and CSP. All six dogs showed initial engraftment, which was sustained in three of the six for >26 weeks, while three dogs rejected their grafts after 9, 22, and 24 weeks, respectively, and survived with autologous recovery. Graft survival was significantly improved over that among 11 historical controls conditioned with 1 Gy TBI and given either MMF or rapamycin with CSP after HCT, all of which rejected their grafts between 3 and 12 weeks (P = 0.03). Preceding donor PBMC infusion and CD154 blockade improved survival of DLA-identical marrow grafts after 1 Gy TBI.",,"['Jochum, Christoph', 'Beste, Mechthild', 'Zellmer, Eustacia', 'Graves, Scott S.', 'Storb, Rainer']",,,,
,PMC,What will become of the polio network?,http://dx.doi.org/10.2471/BLT.07.010207,PMC2636278,,,"Polio could be history within a few years, but what will become of the vast network set up to fight the disease is unclear. Health experts fear that once polio is eradicated, donors will stop funding the diversified network, which now helps immunize children against many other diseases, fight outbreaks and respond to natural disasters.",,"Garwood, Paul",,,,
,PMC,Bulletin Board,,PMC1949132,,,,,,,,,
,PMC,Treatment of hypernatremia in neonatal calves with diarrhea,,PMC1780237,,,"Five hypernatremic, diarrheic, neonatal calves were treated mainly by the intravenous administration of 5% dextrose alone or with isotonic sodium bicarbonate. All calves recovered without complications. The average reduction rate of serum sodium concentration was about 4 times that recommended and has not been tried successfully before in hypernatremic scouring calves.",,"['Abutarbush, Sameeh M.', 'Petrie, Lyall']",,,,
,PMC,Quiz Corner,,PMC1780228,,,,,,,,,
,PMC,HIGH-THROUGHPUT SCREENING FOR NOVEL HUMAN LYSOSOMAL BETA-N-ACETYL HEXOSAMINIDASE INHIBITORS ACTING AS PHARMACOLOGICAL CHAPERONES,http://dx.doi.org/10.1016/j.chembiol.2006.12.006,PMC1989145,,,"The Adult forms of Tay-Sachs (ATSD) and Sandhoff (ASD) diseases result when the activity levels of human β-hexosaminidase A (Hex) fall below ~10% of normal, due to mutations that destabilize the native folded form of the enzyme in the endoplasmic reticulum (ER). The native fold not only conveys activity, but is also required for the transport of the enzyme out of the ER to the lysosome. We have shown that conventional carbohydrate-based competitive inhibitors of purified Hex also act as pharmacological chaperones (PC) in ATSD or ASD cells, overcoming to some extent the destabilizing effects of the mutation, increasing the levels of mutant Hex protein and activity in the lysosome 3–6 fold. We now report the development of a fluorescence-based real-time enzyme assay suitable for high throughput screening of the Maybridge library of 50,000 drug-like compounds to identify novel inhibitors (hits) of purified human Hex. Each hit was then evaluated as a PC in a cell-based assay. Three structurally distinct compounds, a bisnaphthalimide, a nitro-indan-1-one, and a pyrrolo[3,4-d]pyridazin-1-one were identified as micromolar competitive inhibitors of the enzyme that also specifically increased the levels of lysosomal Hex protein and activity in patient fibroblasts.",,"['Tropak, Michael B.', 'Blanchard, Jan', 'Withers, Stephen G.', 'Brown, Eric', 'Mahuran, Don']",,,,
,PMC,"Sequences vs viruses: producer vs product, cause and effect",,PMC2080495,,,,,"Calisher, Charles H.",,,,
,PMC,Sophia,,PMC2658207,,,,,"Wyatt, Coordinated by Simon Binks and Jonathan",,,,
,PMC,Differential type I interferon activation and susceptibility of dendritic cell populations to porcine arterivirus,http://dx.doi.org/10.1111/j.1365-2567.2006.02493.x,PMC2265861,,,"Dendritic cells (DCs) play a role in anti-viral immunity by providing early innate protection against viral replication and by presenting antigen to T cells for initiation of the adaptive immune response. Studies show the adaptive response to porcine reproductive and respiratory syndrome virus (PRRSV) is ineffective for complete viral elimination. Other studies describe the kinetics of the adaptive response to PRRSV, but have not investigated the early response by DCs. We hypothesize that there is an aberrant activation of DCs early in PRRSV infection; consequently, the adaptive response is triggered inadequately. The current study characterized a subtype of porcine lung DCs (L-DCs) and investigated the ability of PRRSV to infect and replicate in L-DCs and monocyte-derived DCs (MDDCs). Furthermore, the type I interferon anti-viral response to PRRSV with and without the addition of recombinant porcine IFN-α (rpIFN-α), an important cytokine that signals for anti-viral mediator activation, was analysed. Results show that PRRSV replicated in MDDCs but not L-DCs, providing evidence that these cells have followed distinct differentiation pathways. Although both cell types responded to PRRSV with an induction of IFN-β mRNA, the magnitude and duration of the response differed between cell types. The addition of rpIFN-α was protective in MDDCs, and mRNA synthesis of Mx (myxovirus resistant) and PKR (double-stranded RNA dependent protein kinase) was observed in both cell types after rpIFN-α addition. Overall, PRRSV replicated in MDDCs but not L-DCs, and rpIFN-α was required for the transcription of protective anti-viral mediators. DC response to PRRSV was limited to IFN-β transcription, which may be inadequate in triggering the adaptive immune response.",,"['Loving, Crystal L', 'Brockmeier, Susan L', 'Sacco, Randy E']",,,,
,PMC,Children's vaccines do not induce cross reactivity against SARS‐CoV,http://dx.doi.org/10.1136/jcp.2006.038893,PMC1860633,,,"In contrast with adults, children infected by severe acute respiratory syndrome‐corona virus (SARS‐CoV) develop milder clinical symptoms. Because of this, it is speculated that children vaccinated with various childhood vaccines might develop cross immunity against SARS‐CoV. Antisera and T cells from mice immunised with various vaccines were used to determine whether they developed cross reactivity against SARS‐CoV. The results showed no marked cross reactivity against SARS‐CoV, which implies that the reduced symptoms among children infected by SARS‐CoV may be caused by other factors.",,"['Yu, Yang', 'Jin, Huali', 'Chen, Ze', 'Yu, Qingling L', 'Ma, Yijie J', 'Sun, Xiaolin L', 'Wang, Bin']",,,,
,PMC,The demise of nursing in the United Kingdom: a warning for medicine,,PMC1790990,,,,,"['Shields, Linda', 'Watson, Roger']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.02684-06,PMC1797534,,,,,,,,,
,PMC,Self-Assembled Combinatorial Encoding Nanoarrays for Multiplexed Biosensing,http://dx.doi.org/10.1021/nl062998n,PMC1963466,,,"Multiplexed and sensitive detection of nucleic acids, proteins, or other molecules from a single solution and a small amount of sample is of great demand in biomarker profiling and disease diagnostics. Here we describe a new concept using combinatorial self-assembly of DNA nanotiles into micrometer-sized two-dimensional arrays that carry nucleic acid probes and barcoded fluorescent dyes to achieve multiplexed detection. We demonstrated the specificity and sensitivity of the arrays by detecting multiple DNA sequences and aptamer binding molecules. This DNA tile-array-based sensor platform can be constructed through DNA self-assembly. The attachment of different molecular probes can be achieved by simple DNA hybridization so bioconjugation is not necessary for the labeling. Accurate control of the interprobe distances and solution-based binding reactions ensures fast target binding kinetics.",,"['Lin, Chenxiang', 'Liu, Yan', 'Yan, Hao']",,,,
,PMC,Leishmaniasis,http://dx.doi.org/10.1136/pgmj.2006.047340corr1,PMC3202701,,,"Epidemiology, disease patterns, immunology, diagnosis, treatment and control measures of leishmaniasis are described. Various issues relating to leishmaniasis are highlighted: the relative lack of importance given to this disease compared with other infections, climate change and its possible impact on extension of endemicity of this infection, and new diagnostic tests which are improving diagnosis, especially in resource poor areas. Other important aspects discussed include the potential for newer oral therapy to change the way this disease is managed; Leishmania–HIV coinfection and groups at risk; and development of an effective vaccine.",,"Piscopo, Tonio V",,,,
,PMC,Long-distance RNA–RNA interactions between terminal elements and the same subset of internal elements on the potato virus X genome mediate minus- and plus-strand RNA synthesis,http://dx.doi.org/10.1261/rna.243607,PMC1781375,,,"Potexvirus genomes contain conserved terminal elements that are complementary to multiple internal octanucleotide elements. Both local sequences and structures at the 5′ terminus and long-distance interactions between this region and internal elements are important for accumulation of potato virus X (PVX) plus-strand RNA in vivo. In this study, the role of the conserved hexanucleotide motif within SL3 of the 3′ NTR and internal conserved octanucleotide elements in minus-strand RNA synthesis was analyzed using both a template-dependent, PVX RNA-dependent RNA polymerase (RdRp) extract and a protoplast replication system. Template analyses in vitro indicated that 3′ terminal templates of 850 nucleotides (nt), but not 200 nt, supported efficient, minus-strand RNA synthesis. Mutational analyses of the longer templates indicated that optimal transcription requires the hexanucleotide motif in SL3 within the 3′ NTR and the complementary CP octanucleotide element 747 nt upstream. Additional experiments to disrupt interactions between one or more internal conserved elements and the 3′ hexanucleotide element showed that long-distance interactions were necessary for minus-strand RNA synthesis both in vitro and in vivo. Additionally, multiple internal octanucleotide elements could serve as pairing partners with the hexanucleotide element in vivo. These cis-acting elements and interactions correlate in several ways to those previously observed for plus-strand RNA accumulation in vivo, suggesting that dynamic interactions between elements at both termini and the same subset of internal octanucleotide elements are required for both minus- and plus-strand RNA synthesis and potentially other aspects of PVX replication.",,"['Hu, Bin', 'Pillai-Nair, Neeta', 'Hemenway, Cynthia']",,,,
,PMC,NKG2D-Mediated Cytotoxicity toward Oligodendrocytes Suggests a Mechanism for Tissue Injury in Multiple Sclerosis,http://dx.doi.org/10.1523/JNEUROSCI.4402-06.2007,PMC6673175,,,"NKG2D is an activating or coactivating receptor expressed on human natural killer (NK) cells, CD8(+) T cells, and γ/δ T cells. NKG2D ligands have been detected on many tumor cell types and can be induced on nontransformed cells by environmental signals including DNA damage and inflammation. We investigated the contribution of NKG2D–NKG2D ligand interaction on CNS-directed immune responses. We observed that primary cultures of human adult oligodendrocytes and fetal astrocytes expressed ligands for NKG2D in vitro whereas neurons, microglia, and adult astrocytes did not. Disruption of the NKG2D–NKG2D ligand interaction using blocking antibodies significantly inhibited killing of primary human oligodendrocytes mediated by activated human NK cells, γ/δ T cells, and allo-reactive CD8(+) T cells. NKG2D ligands [major histocompatibility complex class I chain-related molecules A and B (MICA/B)] were detected in groups of cells and colocalized with an oligodendrocyte marker (adenomatous polyposis coli) in white matter sections obtained from multiple sclerosis lesions but not in normal control samples. CD8(+) T cells could be detected in close proximity to MICA/B+ cells within multiple sclerosis lesions, supporting an in vivo interaction between these immune effectors and stressed MICA/B-expressing oligodendrocytes. These results imply that NKG2D–NKG2D ligand interaction can potentially contribute to cytotoxic responses mediated by activated immune effector cells in the inflamed CNS, as observed in multiple sclerosis.",,"['Saikali, Philippe', 'Antel, Jack P.', 'Newcombe, Jia', 'Chen, Zhihong', 'Freedman, Mark', 'Blain, Manon', 'Cayrol, Romain', 'Prat, Alexandre', 'Hall, Jeffery A.', 'Arbour, Nathalie']",,,,
,PMC,Canine Distemper Virus Infection Requires Cholesterol in the Viral Envelope,http://dx.doi.org/10.1128/JVI.02647-06,PMC1866149,,,"Cholesterol is known to play an important role in stabilizing particular cellular membrane structures, so-called lipid or membrane rafts. For several viruses, a dependence on cholesterol for virus entry and/or morphogenesis has been shown. Using flow cytometry and fluorescence microscopy, we demonstrate that infection of cells by canine distemper virus (CDV) was not impaired after cellular cholesterol had been depleted by the drug methyl-β-cyclodextrin. This effect was independent of the multiplicity of infection and the cellular receptor used for infection. However, cholesterol depletion of the viral envelope significantly reduced CDV infectivity. Replenishment by addition of exogenous cholesterol restored infectivity up to 80%. Thus, we conclude that CDV entry is dependent on cholesterol in the viral envelope. Furthermore, reduced syncytium formation was observed when the cells were cholesterol depleted during the course of the infection. This may be related to the observation that CDV envelope proteins H and F partitioned into cellular detergent-resistant membranes. Therefore, a role for lipid rafts during virus assembly and release as well is suggested.",,"['Imhoff, Heidi', 'von Messling, Veronika', 'Herrler, Georg', 'Haas, Ludwig']",,,,
,PMC,Evolutionary Insights into the Ecology of Coronaviruses,http://dx.doi.org/10.1128/JVI.02605-06,PMC1866124,,,"Although many novel members of the Coronaviridae have recently been recognized in different species, the ecology of coronaviruses has not been established. Our study indicates that bats harbor a much wider diversity of coronaviruses than any other animal species. Dating of different coronavirus lineages suggests that bat coronaviruses are older than those recognized in other animals and that the human severe acute respiratory syndrome (SARS) coronavirus was directly derived from viruses from wild animals in wet markets of southern China. Furthermore, the most closely related bat and SARS coronaviruses diverged in 1986, an estimated divergence time of 17 years prior to the outbreak, suggesting that there may have been transmission via an unknown intermediate host. Analysis of lineage-specific selection pressure also indicated that only SARS coronaviruses in civets and humans were under significant positive selection, also demonstrating a recent interspecies transmission. Analysis of population dynamics revealed that coronavirus populations in bats have constant population growth, while viruses from all other hosts show epidemic-like increases in population. These results indicate that diverse coronaviruses are endemic in different bat species, with repeated introductions to other animals and occasional establishment in other species. Our findings suggest that bats are likely the natural hosts for all presently known coronavirus lineages and that all coronaviruses recognized in other species were derived from viruses residing in bats. Further surveillance of bat and other animal populations is needed to fully describe the ecology and evolution of this virus family.",,"['Vijaykrishna, D.', 'Smith, G. J. D.', 'Zhang, J. X.', 'Peiris, J. S. M.', 'Chen, H.', 'Guan, Y.']",,,,
,PMC,Contemplating annihilation,http://dx.doi.org/10.1136/bmj.39101.510023.B7,PMC1782003,,,,,"Dalrymple, Theodore",,,,
,PMC,STRUCTURE OF A HIGH-AFFINITY “MIMOTOPE” PEPTIDE BOUND TO HIV-1-NEUTRALIZING ANTIBODY b12 EXPLAINS ITS INABILITY TO ELICIT gp120 CROSS-REACTIVE ANTIBODIES,http://dx.doi.org/10.1016/j.jmb.2007.01.060,PMC1995417,,,"The human antibody b12 recognizes a discontinuous epitope on gp120 and is one of the rare monoclonal antibodies that neutralize a broad range of primary HIV-1 isolates. We previously reported the isolation of B2.1, a dimeric peptide that binds with high specificity to b12 and competes with gp120 for b12 antibody binding. Here, we show that the affinity of B2.1 was improved 60-fold over its synthetic-peptide counterpart by fusing it to the N-terminus of a soluble protein. This affinity, which is within an order of magnitude of that of gp120, probably more closely reflects the affinity of the phage-borne peptide. The crystal structure of a complex between Fab of b12 and B2.1 was determined at 1.8 Å resolution. The structural data allowed the differentiation of residues that form critical contacts with b12 from those required for maintenance of the antigenic structure of the peptide, and revealed that three contiguous residues mediate B2.1's critical contacts with b12. This single region of critical contact between the B2.1 peptide and the b12 paratope is unlikely to mimic the discontinuous key binding residues involved in the full b12 epitope for gp120, as previously identified by alanine scanning substitutions on the gp120 surface. These structural observations are supported by experiments that demonstrate that B2.1 is an ineffective immunogenic mimic of the b12 epitope on gp120. Indeed, an extensive series of immunizations with B2.1 in various forms failed to produce gp120 cross-reactive sera. The functional and structural data presented here, however, suggest that the mechanism by which b12 recognizes the two antigens is very different. Here, we present the first crystal structure of peptide bound to an antibody that was originally raised against a discontinuous protein epitope. Our results highlight the challenge of producing immunogens that mimic discontinuous protein epitopes, and the necessity of combining complementary experimental approaches in analyzing the antigenic and immunogenic properties of putative molecular mimics.",,"['Saphire, Erica Ollmann', 'Montero, Marinieve', 'Menendez, Alfredo', 'van Houten, Nienke E.', 'Irving, Melita B.', 'Pantophlet, Ralph', 'Zwick, Michael B.', 'Parren, Paul W. H. I.', 'Burton, Dennis R.', 'Scott, Jamie K.', 'Wilson, Ian A.']",,,,
,PMC,Antiviral Activity and RNA Polymerase Degradation Following Hsp90 Inhibition in a Range of Negative Strand Viruses,http://dx.doi.org/10.1016/j.virol.2006.12.026,PMC1995422,,,"We have analyzed the effectiveness of Hsp90 inhibitors in blocking the replication of negative-strand RNA viruses. In cells infected with the prototype negative strand virus vesicular stomatitis virus (VSV), inhibiting Hsp90 activity reduced viral replication in cells infected at both high and low multiplicities of infection. This inhibition was observed using two Hsp90 inhibitors geldanamycin and radicicol. Silencing of Hsp90 expression using siRNA also reduced viral replication. Hsp90 inhibition changed the half-life of newly synthesized L protein (the large subunit of the VSV polymerase) from >1 hour to less than 15 minutes without affecting the stability of other VSV proteins. Both the inhibition of viral replication and the destabilization of the viral L protein were seen when either geldanamycin or radicicol was added to cells infected with paramyxoviruses SV5, HPIV-2, HPIV-3, or SV41, or to cells infected with the La Crosse bunyavirus. Based these results we propose that Hsp90 is a host factor that is important for the replication of many negative strand viruses.",,"['Connor, John H.', 'McKenzie, Margie O.', 'Parks, Griffith D.', 'Lyles, Douglas S.']",,,,
,PMC,Discovery of Small-Molecule HIV-1 Fusion and Integrase Inhibitors Oleuropein and Hydroxytyrosol: I. Fusion Inhibition,http://dx.doi.org/10.1016/j.bbrc.2007.01.071,PMC2790717,,,"We have identified oleuropein (Ole) and hydroxytyrosol (HT) as a unique class of HIV-1 inhibitors from olive leaf extracts effective against viral fusion and integration. We used molecular docking simulation to study the interactions of Ole and HT with viral targets. We find that Ole and HT bind to the conserved hydrophobic pocket on the surface of the HIV-gp41 fusion domain by hydrogen bonds with Q577 and hydrophobic interactions with I573, G572, and L568 on the gp41 N-terminal heptad repeat peptide N36, interfering with formation of the gp41 fusion-active core. To test and confirm modeling predications, we examined the effect of Ole and HT on HIV-1 fusion complex formation using native polyacrylamide gel electrophoresis and circular dichroism spectroscopy. Ole and HT exhibit dose dependent inhibition on HIV-1 fusion core formation with EC(50)s of 66–58 nM, with no detectable toxicity. Our findings on effects on HIV-1 integrase are reported separately.",,"['Lee-Huang, Sylvia', 'Huang, Philip Lin', 'Zhang, Dawei', 'Lee, Jae Wook', 'Bao, Ju', 'Sun, Yongtao', 'Chang, Young-Tae', 'Zhang, John', 'Huang, Paul Lee']",,,,
,PMC,Human Coronavirus 229E Papain-Like Proteases Have Overlapping Specificities but Distinct Functions in Viral Replication,http://dx.doi.org/10.1128/JVI.02091-06,PMC1866161,,,"Expression of the exceptionally large RNA genomes of CoVs involves multiple regulatory mechanisms, including extensive proteolytic processing of the large replicase polyproteins, pp1a and pp1ab, by two types of cysteine proteases: the chymotrypsin-like main protease and papain-like accessory proteases (PL(pro)s). Here, we characterized the proteolytic processing of the human coronavirus 229E (HCoV-229E) amino-proximal pp1a/pp1ab region by two paralogous PL(pro) activities. Reverse-genetics data revealed that replacement of the PL2(pro) active-site cysteine was lethal. By contrast, the PL1(pro) activity proved to be dispensable for HCoV-229E virus replication, although reversion of the PL1(pro) active-site substitution to the wild-type sequence after several passages in cell culture indicated that there was selection pressure to restore the PL1(pro) activity. Further experiments showed that both PL1(pro) and PL2(pro) were able to cleave the nsp1-nsp2 cleavage site, with PL2(pro) cleaving the site less efficiently. The PL1(pro)-negative mutant genotype could be stably maintained in cell culture when the nsp1-nsp2 site was replaced by a short autoproteolytic sequence, suggesting that the major driving force for the observed reversion of the PL1(pro) mutation was the requirement for efficient nsp1-nsp2 cleavage. The data suggest that the two HCoV-229E PL(pro) paralogs have overlapping substrate specificities but different functions in viral replication. Within the tightly controlled interplay of the two protease activities, PL2(pro) plays a universal and essential proteolytic role that appears to be assisted by the PL1(pro) paralog at specific sites. Functional and evolutionary implications of the differential amino-terminal polyprotein-processing pathways among the main CoV lineages are discussed.",,"['Ziebuhr, John', 'Schelle, Barbara', 'Karl, Nadja', 'Minskaia, Ekaterina', 'Bayer, Sonja', 'Siddell, Stuart G.', 'Gorbalenya, Alexander E.', 'Thiel, Volker']",,,,
,PMC,Spring-Loaded Heptad Repeat Residues Regulate the Expression and Activation of Paramyxovirus Fusion Protein,http://dx.doi.org/10.1128/JVI.02464-06,PMC1866055,,,"During viral entry, the paramyxovirus fusion (F) protein fuses the viral envelope to a cellular membrane. Similar to other class I viral fusion glycoproteins, the F protein has two heptad repeat regions (HRA and HRB) that are important in membrane fusion and can be targeted by antiviral inhibitors. Upon activation of the F protein, HRA refolds from a spring-loaded, crumpled structure into a coiled coil that inserts a hydrophobic fusion peptide into the target membrane and binds to the HRB helices to form a fusogenic hairpin. To investigate how F protein conformational changes are regulated, we mutated in the Sendai virus F protein a highly conserved 10-residue sequence in HRA that undergoes major structural changes during protein refolding. Nine of the 15 mutations studied caused significant defects in F protein expression, processing, and fusogenicity. Conversely, the remaining six mutations enhanced the fusogenicity of the F protein, most likely by helping spring the HRA coil. Two of the residues that were neither located at “a” or “d” positions in the heptad repeat nor conserved among the paramyxoviruses were key regulators of the folding and fusion activity of the F protein, showing that residues not expected to be important in coiled-coil formation may play important roles in regulating membrane fusion. Overall, the data support the hypothesis that regions in the F protein that undergo dramatic changes in secondary and tertiary structure between the prefusion and hairpin conformations regulate F protein expression and activation.",,"['Luque, Laura E.', 'Russell, Charles J.']",,,,
,PMC,Recombinant Protein-Based Assays for Detection of Antibodies to Severe Acute Respiratory Syndrome Coronavirus Spike and Nucleocapsid Proteins,http://dx.doi.org/10.1128/CVI.00351-06,PMC1828864,,,Recombinant severe acute respiratory syndrome (SARS) nucleocapsid and spike protein-based immunoglobulin G immunoassays were developed and evaluated. Our assays demonstrated high sensitivity and specificity to the SARS coronavirus in sera collected from patients as late as 2 years postonset of symptoms. These assays will be useful not only for routine SARS coronavirus diagnostics but also for epidemiological and antibody kinetic studies.,,"['Haynes, Lia M.', 'Miao, Congrong', 'Harcourt, Jennifer L.', 'Montgomery, Joel M.', 'Le, Mai Quynh', 'Dryga, Sergey A.', 'Kamrud, Kurt I.', 'Rivers, Bryan', 'Babcock, Gregory J.', 'Oliver, Jennifer Betts', 'Comer, James A.', 'Reynolds, Mary', 'Uyeki, Timothy M.', 'Bausch, Daniel', 'Ksiazek, Thomas', 'Thomas, William', 'Alterson, Harold', 'Smith, Jonathan', 'Ambrosino, Donna M.', 'Anderson, Larry J.']",,,,
,PMC,Generic Detection of Coronaviruses and Differentiation at the Prototype Strain Level by Reverse Transcription-PCR and Nonfluorescent Low-Density Microarray,http://dx.doi.org/10.1128/JCM.02426-06,PMC1829107,,,"A nonfluorescent low-cost, low-density oligonucleotide array was designed for detecting the whole coronavirus genus after reverse transcription (RT)-PCR. The limit of detection was 15.7 copies/reaction. The clinical detection limit in patients with severe acute respiratory syndrome was 100 copies/sample. In 39 children suffering from coronavirus 229E, NL63, OC43, or HKU1, the sensitivity was equal to that of individual real-time RT-PCRs.",,"['de Souza Luna, Luciano Kleber', 'Heiser, Volker', 'Regamey, Nicolas', 'Panning, Marcus', 'Drexler, Jan Felix', 'Mulangu, Sabue', 'Poon, Leo', 'Baumgarte, Sigrid', 'Haijema, Bert Jan', 'Kaiser, Laurent', 'Drosten, Christian']",,,,
,PMC,Ribonucleocapsid Formation of Severe Acute Respiratory Syndrome Coronavirus through Molecular Action of the N-Terminal Domain of N Protein,http://dx.doi.org/10.1128/JVI.02236-06,PMC1866093,,,"Conserved among all coronaviruses are four structural proteins: the matrix (M), small envelope (E), and spike (S) proteins that are embedded in the viral membrane and the nucleocapsid phosphoprotein (N), which exists in a ribonucleoprotein complex in the lumen. The N-terminal domain of coronaviral N proteins (N-NTD) provides a scaffold for RNA binding, while the C-terminal domain (N-CTD) mainly acts as oligomerization modules during assembly. The C terminus of the N protein anchors it to the viral membrane by associating with M protein. We characterized the structures of N-NTD from severe acute respiratory syndrome coronavirus (SARS-CoV) in two crystal forms, at 1.17 Å (monoclinic) and at 1.85 Å (cubic), respectively, resolved by molecular replacement using the homologous avian infectious bronchitis virus (IBV) structure. Flexible loops in the solution structure of SARS-CoV N-NTD are now shown to be well ordered around the β-sheet core. The functionally important positively charged β-hairpin protrudes out of the core, is oriented similarly to that in the IBV N-NTD, and is involved in crystal packing in the monoclinic form. In the cubic form, the monomers form trimeric units that stack in a helical array. Comparison of crystal packing of SARS-CoV and IBV N-NTDs suggests a common mode of RNA recognition, but they probably associate differently in vivo during the formation of the ribonucleoprotein complex. Electrostatic potential distribution on the surface of homology models of related coronaviral N-NTDs suggests that they use different modes of both RNA recognition and oligomeric assembly, perhaps explaining why their nucleocapsids have different morphologies.",,"['Saikatendu, Kumar Singh', 'Joseph, Jeremiah S.', 'Subramanian, Vanitha', 'Neuman, Benjamin W.', 'Buchmeier, Michael J.', 'Stevens, Raymond C.', 'Kuhn, Peter']",,,,
,PMC,The Glycoprotein Cytoplasmic Tail of Uukuniemi Virus (Bunyaviridae) Interacts with Ribonucleoproteins and Is Critical for Genome Packaging,http://dx.doi.org/10.1128/JVI.02655-06,PMC1866086,,,"We have analyzed the importance of specific amino acids in the cytoplasmic tail of the glycoprotein G(N) for packaging of ribonucleoproteins (RNPs) into virus-like particles (VLPs) of Uukuniemi virus (UUK virus), a member of the Bunyaviridae family. In order to study packaging, we added the G(N)/G(C) glycoprotein precursor (p110) to a polymerase I-driven minigenome rescue system to generate VLPs that are released into the supernatant. These particles can infect new cells, and reporter gene expression can be detected. To determine the role of UUK virus glycoproteins in RNP packaging, we performed an alanine scan of the glycoprotein G(N) cytoplasmic tail (amino acids 1 to 81). First, we discovered three regions in the tail (amino acids 21 to 25, 46 to 50, and 71 to 81) which are important for minigenome transfer by VLPs. Further mutational analysis identified four amino acids that were important for RNP packaging. These amino acids are essential for the binding of nucleoproteins and RNPs to the glycoprotein without affecting the morphology of the particles. No segment-specific interactions between the RNA and the cytoplasmic tail could be observed. We propose that VLP systems are useful tools for analyzing protein-protein interactions important for packaging of viral genome segments, assembly, and budding of other members of the Bunyaviridae family.",,"['Överby, Anna K.', 'Pettersson, Ralf F.', 'Neve, Etienne P. A.']",,,,
,PMC,5′-Proximal Hot Spot for an Inducible Positive-to-Negative-Strand Template Switch by Coronavirus RNA-Dependent RNA Polymerase,http://dx.doi.org/10.1128/JVI.01817-06,PMC1866079,,,"Coronaviruses have a positive-strand RNA genome and replicate through the use of a 3′ nested set of subgenomic mRNAs each possessing a leader (65 to 90 nucleotides [nt] in length, depending on the viral species) identical to and derived from the genomic leader. One widely supported model for leader acquisition states that a template switch takes place during the generation of negative-strand antileader-containing templates used subsequently for subgenomic mRNA synthesis. In this process, the switch is largely driven by canonical heptameric donor sequences at intergenic sites on the genome that match an acceptor sequence at the 3′ end of the genomic leader. With experimentally placed 22-nt-long donor sequences within a bovine coronavirus defective interfering (DI) RNA we have shown that matching sites occurring anywhere within a 65-nt-wide 5′-proximal genomic acceptor hot spot (nt 33 through 97) can be used for production of templates for subgenomic mRNA synthesis from the DI RNA. Here we report that with the same experimental approach, template switches can be induced in trans from an internal site in the DI RNA to the negative-strand antigenome of the helper virus. For these, a 3′-proximal 89-nt acceptor hot spot on the viral antigenome (nt 35 through 123), largely complementary to that described above, was found. Molecules resulting from these switches were not templates for subgenomic mRNA synthesis but, rather, ambisense chimeras potentially exceeding the viral genome in length. The results suggest the existence of a coronavirus 5′-proximal partially double-stranded template switch-facilitating structure of discrete width that contains both the viral genome and antigenome.",,"['Wu, Hung-Yi', 'Brian, David A.']",,,,
,PMC,Role of the Coronavirus E Viroporin Protein Transmembrane Domain in Virus Assembly,http://dx.doi.org/10.1128/JVI.01472-06,PMC1866030,,,"Coronavirus envelope (E) proteins are small (∼75- to 110-amino-acid) membrane proteins that have a short hydrophilic amino terminus, a relatively long hydrophobic membrane domain, and a long hydrophilic carboxy-terminal domain. The protein is a minor virion structural component that plays an important, not fully understood role in virus production. It was recently demonstrated that the protein forms ion channels. We investigated the importance of the hydrophobic domain of the mouse hepatitis coronavirus (MHV) A59 E protein. Alanine scanning insertion mutagenesis was used to examine the effect of disruption of the domain on virus production in the context of the virus genome by using a MHV A59 infectious clone. Mutant viruses exhibited smaller plaque phenotypes, and virus production was significantly crippled. Analysis of recovered viruses suggested that the structure of the presumed α-helical structure and positioning of polar hydrophilic residues within the predicted transmembrane domain are important for virus production. Generation of viruses with restored wild-type helical pitch resulted in increased virus production, but some exhibited decreased virus release. Viruses with the restored helical pitch were more sensitive to treatment with the ion channel inhibitor hexamethylene amiloride than were the more crippled parental viruses with the single alanine insertions, suggesting that disruption of the transmembrane domain affects the functional activity of the protein. Overall the results indicate that the transmembrane domain plays a crucial role during biogenesis of virions.",,"['Ye, Ye', 'Hogue, Brenda G.']",,,,
,PMC,Significance of Fomites in the Spread of Respiratory and Enteric Viral Disease,http://dx.doi.org/10.1128/AEM.02051-06,PMC1828811,,,,,"['Boone, Stephanie A.', 'Gerba, Charles P.']",,,,
,PMC,Duration and distance of exposure are important predictors of transmission among community contacts of Ontario SARS cases,http://dx.doi.org/10.1017/S0950268806007771,PMC2870656,,,"We report attack rates and contact-related predictors among community contacts of severe acute respiratory syndrome (SARS) cases from the 2003 Toronto-area outbreak. Community contact data was extracted from public health records for single, well-defined exposures to a SARS case. In total, 8662 community-acquired exposures resulted in 61 probable cases; a crude attack rate of 0·70% [95% confidence interval (CI) 0·54–0·90]. Persons aged 55–69 years were at higher risk of acquiring SARS (1·14%) than those either younger (0·60%) or older (0·70%). In multivariable analysis exposures for at least 30 min at a distance of ⩽1 m increased the likelihood of becoming a SARS case 20·4-fold (95% CI 11·8–35·1). Risk related to duration of illness in the source case at time of exposure was greatest for illness duration of 7–10 days (rate ratio 3·4, 95% CI 1·9–6·1). Longer and closer proximity exposures incurred the highest rate of disease. Separate measures of time and distance from source cases should be added to minimum datasets for the assessment of interventions for SARS and other emerging diseases.",,"['REA, E.', 'LAFLÈCHE, J.', 'STALKER, S.', 'GUARDA, B.\xa0K.', 'SHAPIRO, H.', 'JOHNSON, I.', 'BONDY, S.\xa0J.', 'UPSHUR, R.', 'RUSSELL, M.\xa0L.', 'ELIASZIW, M.']",,,,
,PMC,Membrane Topology of Murine Coronavirus Replicase Nonstructural Protein 3,http://dx.doi.org/10.1016/j.virol.2006.12.009,PMC1925034,,,"Mouse hepatitis virus (MHV) is a member of the family Coronaviridae. These positive strand RNA viruses encode a replicase polyprotein that is processed into 16 nonstructural proteins (nsps). The nsps assemble with membranes to generate double membrane vesicles, which are the sites of viral RNA synthesis. MHV nsp3 contains multiple domains including two papain-like protease domains, PLP1 and PLP2, and a predicted transmembrane (TM) domain. In this study, we determined the membrane topology of nsp3-TM and showed that TM-mediated tethering of PLP2 is important for processing at cleavage site 3. Biochemical analysis revealed that nsp3 is an integral membrane protein that is inserted into endoplasmic reticulum (ER) membranes co-translationally and glycosylated at asparagine-2357. Proteinase K digestion experiments indicate that the TM domain of nsp3 has 4 membrane-spanning helices. We show that nsp3-TM is sufficient to mediate ER membrane association of a cytosolic protein. This study is the first detailed analysis of the topology and function of the coronavirus nsp3 TM domain.",,"['Kanjanahaluethai, Amornrat', 'Chen, Zhongbin', 'Jukneliene, Dalia', 'Baker, Susan C.']",,,,
,PMC,Recombinant Truncated Nucleocapsid Protein as Antigen in a Novel Immunoglobulin M Capture Enzyme-Linked Immunosorbent Assay for Diagnosis of Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/CVI.00360-06,PMC1797799,,,"We report the development of an immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) for severe acute respiratory syndrome coronavirus (SARS-CoV) by using recombinant truncated SARS-CoV nucleocapsid protein as the antigen. The newly developed MAC-ELISA had a specificity and sensitivity of 100% as evaluated by using sera from healthy volunteers and patients with laboratory-confirmed SARS. Using serial serum samples collected from SARS patients, the times to seroconversion were determined by IgM antibody detection after SARS-CoV infection. The median time to seroconversion detection was 8 days (range, 5 to 17 days) after disease onset, and the seroconversion rates after the onset of illness were 33% by the first week, 97% by the second week, and 100% by the third week. Compared with the results of our previous report on the detection of IgG, the median seroconversion time by IgM detection was 3 days earlier and the seroconversion rate by the second week after the illness for IgM was significantly higher than by IgG assay. Our results indicating that the IgM response appears earlier than IgG after SARS-CoV infection in consistent with those for other pathogens. Our newly developed MAC-ELISA system offers a new alternative for the confirmation of SARS-CoV infection.",,"['Yu, Fuxun', 'Le, Mai Quynh', 'Inoue, Shingo', 'Hasebe, Futoshi', 'Parquet, Maria del Carmen', 'Morikawa, Shigeru', 'Morita, Kouichi']",,,,
,PMC,Characterization of the Nuclear Export Signal in the Coronavirus Infectious Bronchitis Virus Nucleocapsid Protein,http://dx.doi.org/10.1128/JVI.02239-06,PMC1866115,,,"The nucleocapsid (N) protein of infectious bronchitis virus (IBV) localizes to the cytoplasm and nucleolus and contains an eight-amino-acid nucleolar retention motif. In this study, a leucine-rich nuclear export signal (NES) (291-LQLDGLHL-298) present in the C-terminal region of the IBV N protein was analyzed by using alanine substitution and deletion mutagenesis to investigate the relative contributions that leucine residues make to nuclear export and where these residues are located on the structure of the IBV N protein. The analysis indicated that Leu296 and Leu298 are required for efficient nuclear export of the protein. Structural information indicated that both of these amino acids are available for interaction with protein complexes involved in this process. However, export of N protein from the nucleus/nucleolus was not inhibited by leptomycin B treatment, indicating that N protein nuclear export is independent of the CRM1-mediated export pathway.",,"['Reed, Mark L.', 'Howell, Gareth', 'Harrison, Sally M.', 'Spencer, Kelly-Anne', 'Hiscox, Julian A.']",,,,
,PMC,Novel β-Barrel Fold in the Nuclear Magnetic Resonance Structure of the Replicase Nonstructural Protein 1 from the Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.01939-06,PMC1866046,,,"The nonstructural protein 1 (nsp1) of the severe acute respiratory syndrome coronavirus has 179 residues and is the N-terminal cleavage product of the viral replicase polyprotein that mediates RNA replication and processing. The specific function of nsp1 is not known. Here we report the nuclear magnetic resonance structure of the nsp1 segment from residue 13 to 128, which represents a novel α/β-fold formed by a mixed parallel/antiparallel six-stranded β-barrel, an α-helix covering one opening of the barrel, and a 3(10)-helix alongside the barrel. We further characterized the full-length 179-residue protein and show that the polypeptide segments of residues 1 to 12 and 129 to 179 are flexibly disordered. The structure is analyzed in a search for possible correlations with the recently reported activity of nsp1 in the degradation of mRNA.",,"['Almeida, Marcius S.', 'Johnson, Margaret A.', 'Herrmann, Torsten', 'Geralt, Michael', 'Wüthrich, Kurt']",,,,
,PMC,Enzymatic Defects of the nsP2 Proteins of Semliki Forest Virus Temperature-Sensitive Mutants,http://dx.doi.org/10.1128/JVI.02078-06,PMC1866018,,,"We have analyzed the biochemical consequences of mutations that affect viral RNA synthesis in Semliki Forest virus temperature-sensitive (ts) mutants. Of the six mutations mapping in the multifunctional replicase protein nsP2, three were located in the N-terminal helicase region and three were in the C-terminal protease domain. Wild-type and mutant nsP2s were expressed, purified, and assayed for nucleotide triphosphatase (NTPase), RNA triphosphatase (RTPase), and protease activities in vitro at 24°C and 35°C. The protease domain mutants (ts4, ts6, and ts11) had reduced protease activity at 35°C but displayed normal NTPase and RTPase. The helicase domain mutation ts1 did not have enzymatic consequences, whereas ts13a and ts9 reduced both NTPase and protease activities but in different and mutant-specific ways. The effects of these helicase domain mutants on protease function suggest interdomain interactions within nsP2. NTPase activity was not directly required for protease activity. The similarities of the NTPase and RTPase results, as well as competition experiments, suggest that these two reactions utilize the same active site. The mutations were also studied in recombinant viruses first cultivated at the permissive temperature and then shifted up to the restrictive temperature. Processing of the nonstructural polyprotein was generally retarded in cells infected with viruses carrying the ts4, ts6, ts11, and ts13a mutations, and a specific defect appeared in ts9. All mutations except ts13a were associated with a large reduction in the production of the subgenomic 26S mRNA, indicating that both protease and helicase domains influence the recognition of the subgenomic promoter during virus replication.",,"['Balistreri, Giuseppe', 'Caldentey, Javier', 'Kääriäinen, Leevi', 'Ahola, Tero']",,,,
,PMC,Andes and Prospect Hill Hantaviruses Differ in Early Induction of Interferon although Both Can Downregulate Interferon Signaling,http://dx.doi.org/10.1128/JVI.02402-06,PMC1866013,,,"Hantavirus pulmonary syndrome (HPS) is a severe respiratory disease which is thought to result from a dysregulated immune response to infection with pathogenic hantaviruses, such as Sin Nombre virus or Andes virus (ANDV). Other New World hantaviruses, such as Prospect Hill virus (PHV), have not been associated with human disease. Activation of an antiviral state and cell signaling in response to hantavirus infection were examined using human primary lung endothelial cells, the main target cell infected in HPS patients. PHV, but not ANDV, was found to induce a robust beta interferon (IFN-β) response early after infection of primary lung endothelial cells. The level of IFN induction correlated with IFN regulatory factor 3 (IRF-3) activation, in that IRF-3 dimerization and nuclear translocation were detected in PHV but not ANDV infection. In addition, phosphorylated Stat-1/2 levels were significantly lower in the ANDV-infected cells relative to PHV. Presumably, this reflects the lower level of IRF-3 activation and initial IFN induced by ANDV relative to PHV. To determine whether, in addition, ANDV interference with IFN signaling also contributed to the low Stat-1/2 activation seen in ANDV infection, the levels of exogenous IFN-β-induced Stat-1/2 activation detectable in uninfected versus ANDV- or PHV-infected Vero-E6 cells were examined. Surprisingly, both viruses were found to downregulate IFN-induced Stat-1/2 activation. Analysis of cells transiently expressing only ANDV or PHV glycoproteins implicated these proteins in this downregulation. In conclusion, while both viruses can interfere with IFN signaling, there is a major difference in the initial interferon induction via IRF-3 activation between ANDV and PHV in infected primary endothelial cells, and this correlates with the reported differences in pathogenicity of these viruses.",,"['Spiropoulou, Christina F.', 'Albariño, César G.', 'Ksiazek, Thomas G.', 'Rollin, Pierre E.']",,,,
,PMC,Rescue of chimeric adenoviral vectors to expand the serotype repertoire,http://dx.doi.org/10.1016/j.jviromet.2006.11.022,PMC1868475,,,"The successful use of any adenoviral vectors is predicated upon the use of a serotype that is not neutralized by circulating antibodies. However, efforts to develop a diverse repertoire of serologically distinct adenovirus vectors may be hindered by the necessity to generate cell lines to allow for the successful propagation of vectors deleted of essential genes. A strategy to construct chimeric adenoviruses whereby the rescue and propagation of an E1 deleted HAdV-B – derived adenoviral vector can be achieved using existing cell lines such as HEK 293 is reported. It is further shown that this strategy may be more widely applicable.",,"['Roy, Soumitra', 'Clawson, David S.', 'Lavrukhin, Oleg', 'Sandhu, Arbans', 'Miller, Jim', 'Wilson, James M.']",,,,
,PMC,Regulation of Autophagy by Extracellular Signal-Regulated Protein Kinases During 1-Methyl-4-Phenylpyridinium-Induced Cell Death,http://dx.doi.org/10.2353/ajpath.2007.060524,PMC1762689,,,"Increased autophagic vacuoles (AVs) occur in injured or degenerating neurons, under both developmental and pathological situations. Although regulation of starvation-induced autophagy has been extensively studied, less is known about autophagic responses to pathological damage. The neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) produces mitochondria-targeted injury, which contributes to parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine in mammals. Here, we demonstrate that MPP(+) elicited increased autophagy in SH-SY5Y cells, as assessed by electron microscopy, immunofluorescence for the autophagy protein LC3/Atg8, LC3 electrophoretic mobility shift, mitochondrial degradation, and monodansylcadaverine staining for late AVs/autolysosomes. During nutrient deprivation, class III phosphatidylinositol-3 kinase (PI3K) stimulates autophagy in concert with the autophagy-regulatory protein beclin 1/Atg6. Although PI3K inhibitors and RNA interference knockdown of beclin 1 effectively inhibited autophagy elicited by amino acid deprivation, neither reduced MPP(+)-induced autophagic stress. In contrast, inhibition of mitogen-activated protein kinase/extracellular signal-regulated protein kinase kinase reduced AV content, mitochondrial degradation, and cell death in MPP(+)-treated cells. RNA interference studies targeting core Atg proteins also reduced AV content and cell death. Likewise, in primary midbrain dopaminergic neurons, MPP(+) elicited increased AV content, which was reversed by inhibition of mitogen-activated protein kinase/extracellular signal-regulated protein kinase kinase but not PI3K. These results implicate a role for extracellular signal-regulated protein kinase (ERK) signaling upstream of MPP(+)-elicited autophagic stress. Moreover, pathological stimulation of beclin 1-independent autophagy is associated with neuronal cell death.",,"['Zhu, Jian-hui', 'Horbinski, Craig', 'Guo, Fengli', 'Watkins, Simon', 'Uchiyama, Yasuo', 'Chu, Charleen T.']",,,,
,PMC,Contrasting Roles for Axonal Degeneration in an Autoimmune versus Viral Model of Multiple Sclerosis : When Can Axonal Injury Be Beneficial?,http://dx.doi.org/10.2353/ajpath.2007.060683,PMC1762678,,,"Although demyelination is a cardinal feature in multiple sclerosis, axonal injury also occurs. We tested whether a delay in axonal degeneration could affect the disease severity in two models for multiple sclerosis: experimental autoimmune encephalomyelitis (EAE) and Theiler’s murine encephalomyelitis virus (TMEV) infection. We compared wild-type C57BL/6 (B6) mice with C57BL/Wld(s) (Wld) mice, which carry a mutation that delays axonal degeneration. In EAE, both mouse strains were sensitized with myelin oligodendrocyte glycoprotein (MOG)(35-55) peptide and showed a similar disease onset, MOG-specific lymphoproliferative responses, and inflammation during the acute stage of EAE. However, during the chronic stage, B6 mice continued to show paralysis with a greater extent of axonal damage, demyelination, and MOG-specific lymphoproliferative responses compared with Wld mice, which showed complete recovery. In TMEV infection, only Wld mice were paralyzed and had increased inflammation, virus antigen-positive cells, and TMEV-specific lymphoproliferative responses versus infected B6 mice. Because TMEV can use axons to disseminate in the brain, axonal degeneration in B6 mice might be a beneficial mechanism that limits the virus spread, whereas slow axonal degeneration in Wld mice could favor virus spread. Therefore, axonal degeneration plays contrasting roles (beneficial versus detrimental) depending on the initiator driving the disease.",,"['Tsunoda, Ikuo', 'Tanaka, Tomoko', 'Terry, Emily Jane', 'Fujinami, Robert S.']",,,,
,PMC,Polio will soon be history,http://dx.doi.org/10.2471/BLT.07.100107,PMC2636221,,,,,,,,,
,PMC,Ten years of fighting bird flu,http://dx.doi.org/10.2471/BLT.07.010107,PMC2636215,,,"This year marks a decade since the first human outbreak of H5N1 avian influenza in Hong Kong. Since then, US $1.9 billion has been pledged to fight avian influenza and a global effort is under way to prevent and be prepared for a pandemic.",,"Parry, Jane",,,,
,PMC,Infection control during gastrointestinal endoscopy,,PMC2656624,,,,,"['Nelson, Douglas B', 'Adams, Paul C']",,,,
,PMC,"AMMI Canada–CACMID 2007 Annual Conference March 14 to 18, 2007: World Trade and Convention Centre, Halifax, Nova Scotia",,PMC2542894,,,,,,,,,
,PMC,Realms of the Viruses Online,http://dx.doi.org/10.1187/cbe.07-09-0067,PMC2104509,,,,,"Liu, Dennis",,,,
,PMC,Role of Cell Culture for Virus Detection in the Age of Technology,http://dx.doi.org/10.1128/CMR.00002-06,PMC1797634,,,"Viral disease diagnosis has traditionally relied on the isolation of viral pathogens in cell cultures. Although this approach is often slow and requires considerable technical expertise, it has been regarded for decades as the “gold standard” for the laboratory diagnosis of viral disease. With the development of nonculture methods for the rapid detection of viral antigens and/or nucleic acids, the usefulness of viral culture has been questioned. This review describes advances in cell culture-based viral diagnostic products and techniques, including the use of newer cell culture formats, cryopreserved cell cultures, centrifugation-enhanced inoculation, precytopathogenic effect detection, cocultivated cell cultures, and transgenic cell lines. All of these contribute to more efficient and less technically demanding viral detection in cell culture. Although most laboratories combine various culture and nonculture approaches to optimize viral disease diagnosis, virus isolation in cell culture remains a useful approach, especially when a viable isolate is needed, if viable and nonviable virus must be differentiated, when infection is not characteristic of any single virus (i.e., when testing for only one virus is not sufficient), and when available culture-based methods can provide a result in a more timely fashion than molecular methods.",,"['Leland, Diane S.', 'Ginocchio, Christine C.']",,,,
,PMC,Polymorphisms in the mannose binding lectin-2 gene and acute respiratory distress syndrome,http://dx.doi.org/10.1097/01.CCM.0000251132.10689.F3,PMC3090269,,,"OBJECTIVE: The variant alleles in the mannose binding lectin-2 (MBL-2) gene have been associated with MBL deficiency and increased susceptibility to sepsis. We postulate that the variant MBL-2 genotypes are associated with increased susceptibility to and mortality in acute respiratory distress syndrome (ARDS). DESIGN: Nested case-control study. SETTING: Tertiary academic medical center. PATIENTS: Two hundred and twelve Caucasians with ARDS and 442 controls genotyped for the variant X, D, B, and C alleles of codon -221, 52, 54, and 57, respectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients homozygous for the variant codon 54B allele (54BB) had worse severity of illness on admission (p = .007), greater likelihood of septic shock (p = .04), and increased odds of ARDS (adjusted odds ratio, 6.7; 95% confidence interval, 1.5-31) when compared with heterozygotes and homozygotes for the wild-type allele. This association with ARDS was especially strong among the 311 patients with septic shock (adjusted odds ratio, 12.0; 95% confidence interval, 1.9-74). Among the patients with ARDS, the 54BB genotype was associated with more daily organ dysfunction (p = .01) and higher mortality (adjusted hazard rate, 4.0; 95% confidence interval, 1.6-10). Development of ARDS and outcomes in ARDS did not vary significantly with variant alleles of codon -221, 52, and 57, but the power to detect an effect was limited secondary to the low allele frequencies. CONCLUSIONS: The MBL-2 codon 54BB genotype may be important in ARDS susceptibility and outcome. Additional studies are needed to confirm these findings in other populations.",,"['Gong, Michelle N.', 'Zhou, Wei', 'Williams, Paige L.', 'Thompson, B. Taylor', 'Pothier, Lucille', 'Christiani, David C.']",,,,
,PMC,Gene Modulation for Treating Liver Fibrosis,,PMC2788157,,,"Despite tremendous progress in our understanding of fibrogenesis, injury stimuli process, inflammation, and hepatic stellate cells (HSC) activation, there is still no standard treatment for liver fibrosis. Delivery of small molecular weight drug, proteins and nucleic acids to specific liver cell types remains a challenge due to the overexpression of extra cellular matrix (ECM) and consequent closure of sinusoidal gaps. In addition, activation of HSCs and subsequent release of inflammatory cytokines and infiltration of immune cells are other major obstacles to the treatment of liver fibrosis. To overcome these barriers, different therapeutic approaches are being investigated. Among them, modulation of certain aberrant protein production is quite promising for treating liver fibrosis. In this review, we will describe the mechanism of antisense, antigene and RNA interference (RNAi) therapies, and will discuss how the backbone modification of oligonucleotides affects their in vivo stability, biodistribution and bioactivity. Strategies for delivering these nucleic acids to specific cell types will be discussed. This review will critically address various insights developed in each individual strategy and for multipronged approaches, which will be helpful in achieving better outcomes.",,"['Cheng, Kun', 'Mahato, Ram I.']",,,,
,PMC,Respiratory viral diseases: access to RNA interference therapy,http://dx.doi.org/10.1016/j.ddstr.2008.01.001,PMC2597863,,,This review summarizes recent experimental achievements in the area of the development of new RNA interference (RNAi) therapeutics for the treatment of viral respiratory diseases. Delivery of siRNA to their intended target tissue remains the biggest problem for most therapeutic applications of these compounds. Appropriate formulations and chemical modifications for improved stability will boost the probability of utilization of RNAi drugs in the clinical applications.,,"['Bitko, Vira', 'Barik, Sailen']",,,,
,PMC,9th Annual Conference on New and Re-emerging Infectious Diseases,http://dx.doi.org/10.3201/eid1301.061158,PMC2725818,,NO-CC CODE,,2007 Jan,"['Wilson, Brenda A.', 'Kitron, Uriel']",Emerg Infect Dis,,,
,PMC,Patients' perceptions of nasopharyngeal aspiration in the emergency department of a teaching hospital in Hong Kong,http://dx.doi.org/10.1136/emj.2006.039701,PMC2658151,,,"Nasopharyngeal aspiration (NPA) is the preferred method for collecting specimens for viral culture in patients with respiratory tract infection. As virus identification may influence admission and treatment decisions, it is important to perform NPA in the emergency department. The test may be uncomfortable and poorly tolerated. This prospective study investigated patients' perceptions of NPA. Patients in the emergency department with upper respiratory tract infection undergoing NPA between 9 March 2005 and 12 August 2005 were included. 86 patients (mean (SD) age 47 (23) years; 49 women) were recruited. 22 (26%) patients complained that NPA was very uncomfortable, 59 (69%) reported that it was mildly uncomfortable and 5 (6%) patients reported no discomfort. On a 10‐point scale, the median discomfort score was 4. 29 (34%) patients stated that NPA was more uncomfortable than blood taking, 19 (22%) patients felt that both were similar and 38 (44%) patients felt that NPA was less uncomfortable (p value not significant). NPA performed in the emergency department is well tolerated and should be considered in emergency departments when results may influence patient management.",,"['Wai, A K C', 'Kwok, W O', 'Chan, M S', 'Graham, C A', 'Rainer, T H']",,,,
,PMC,The psychological effect of severe acute respiratory syndrome on emergency department staff,http://dx.doi.org/10.1136/emj.2006.035089,PMC2658141,,,"BACKGROUND: The severe acute respiratory syndrome (SARS) outbreak in 2003 affected 29 countries. The SARS outbreak was unique in its rapid transmission and it resulted in heavy stress in first‐line healthcare workers, particularly in the emergency department. AIM: : To determine the influence of SARS on the psychological status, including post‐traumatic stress disorder (PTSD) symptoms, of the staff in the emergency department. METHODS: To investigate whether different working conditions in the hospital led to different psychological effects on healthcare workers, the psychological effect on emergency department staff in the high‐risk ward was compared with that on psychiatric ward staff in the medium‐risk ward. Davidson Trauma Scale‐Chinese version (DTS‐C) and Chinese Health Questionnaire‐12 (CHQ‐12) items were designed to check the psychological status of the staff in the month after the end of the SARS outbreak. RESULTS: 86 of 92 (93.5%) medical staff considered the SARS outbreak to be a traumatic experience. The DTS‐C scores of staff in the emergency department and in the psychiatric ward were significantly different (p = 0.04). No significant difference in CHQ score was observed between the two groups. Emergency department staff had more severe PTSD symptoms than staff in the psychiatric ward. CONCLUSION: SARS was a traumatic experience for healthcare providers in Taiwan. Most staff in the emergency department and in the psychiatric ward had PTSD. Emergency department staff had more severe PTSD symptoms than staff in the psychiatric ward.",,"['Lin, C‐Y', 'Peng, Y‐C', 'Wu, Y‐H', 'Chang, J', 'Chan, C‐H', 'Yang, D‐Y']",,,,
,PMC,Silencing of natural interferon producing cell activation by porcine circovirus type 2 DNA,http://dx.doi.org/10.1111/j.1365-2567.2006.02476.x,PMC2265874,,,"Porcine circovirus type 2 (PCV2) infection of natural interferon producing cells (NIPCs) impairs the induction of interferon (IFN)-α and tumour necrosis factor (TNF)-α by cytosine-phosphorothioate-guanine (CpG) oligodeoxynucleotides (ODNs), thereby preventing both their autocrine maturation and the paracrine maturation of myeloid dendritic cells (DCs). The present study shows that the PCV2-mediated inhibition of NIPCs was mediated by viral DNA, although it was independent of virus replication. The inhibitory effect of PCV2 DNA was more diversified than if it had simply targeted CpG-ODN-induced cytokines (IFN-α, TNF-α, interleukin-6, IL-12). A broad spectrum inhibition was noted, affecting responses induced by toll-like receptor (TLR)-7 and TLR9 agonists, as well as viruses including pseudorabies virus, transmissible gastroenteritis virus and classical swine fever virus. From these results, it would appear that PCV2 DNA can induce a dominant negative signal influencing independent pattern recognition receptor-induced activation cascades. Despite a concomitant internalization of PCV2 DNA and CpG-ODNs, no colocalization was observed, indicating that PCV2 DNA and CPG-ODNs may not target the same receptor. This study describes a novel modulation of the innate immune response, which would render the host more susceptible to secondary or concomitant microbial infections.",,"['Vincent, Isabelle E', 'Balmelli, Carole', 'Meehan, Brian', 'Allan, Gordon', 'Summerfield, Artur', 'McCullough, Kenneth C']",,,,
,PMC,Severe Acute Respiratory Syndrome : An Update,http://dx.doi.org/10.1016/S0377-1237(07)80110-9,PMC4921718,,,,,"['Mehta, SR', 'Sashindran, VK', 'Kumar, K', 'Gupta, A']",,,,
,PMC,Training for and Maintaining Public Health Surge Capacity: A Program for Disease Outbreak Investigation by Student Volunteers,,PMC1802123,,,,,"['Eric N., Gebbie', 'Stephen S., Morse', 'Heather, Hanson', 'Michael C., McCollum', 'Vasudha, Reddy', 'Kristine M., Gebbie', 'Elizabeth, Smailes', 'Sharon, Balter']",,,,
,PMC,Systemic Infections Cause Exaggerated Local Inflammation in Atherosclerotic Coronary Arteries: Clues to the Triggering Effect of Acute Infections on Acute Coronary Syndromes,,PMC1847934,,,"Systemic infections can trigger heart attacks. We conducted an autopsy study to investigate the pathologic effect of systemic infections on coronary artery inflammation. We studied 14 atherosclerotic patients diagnosed with an acute systemic infection. Our control group (n=13) had atherosclerosis without infection. The groups were similar in luminal stenosis and age. Coronary artery sections were stained with H&E and markers for macrophages (CD68), T cells (CD3), and dendritic cells (S100). On pathologic examination, 5 infected patients had acute myocardial infarction with thrombosis. Macrophage density in plaques and in periadventitial fat was higher in the infected group (NS). The infected patients' adventitia had significantly more macrophages (1,577 ± 1,872 vs 265 ± 185 per mm(2); P=0.047). The macrophage density, similar in the control group's adventitia and plaque, was significantly greater in the infected group's adventitia than in the plaque. The adventitia and periadventitial fat of the infected group had more T cells than did samples from the control group (48.4 ± 45.0 vs 14.1 ± 6.3 per mm(2); P=0.002). The groups exhibited similar plaque T-cell density. The infected patients' plaques, but not the adventitia and periadventitial fat, had more dendritic cells than did the controls' (3.2 ± 2.5 vs 0.3 ± 0.5 per mm(2); P=0.022). To our knowledge, this is the 1st report to establish a connection between acute systemic infections and significant increases in inflammatory cells in the atherosclerotic coronary arteries of human beings. This offers a new therapeutic target for preventing heart attacks in high-risk patients.",,"['Madjid, Mohammad', 'Vela, Deborah', 'Khalili-Tabrizi, Hessam', 'Casscells, S. Ward', 'Litovsky, Silvio']",,,,
,PMC,Priorities for respiratory research in the UK,http://dx.doi.org/10.1136/thx.2006.073882,PMC2111270,,,Respiratory diseases are placing an increasing burden on the UK health system,,"Holgate, Stephen T",,,,
,PMC,"Two Complex, Adenovirus-Based Vaccines That Together Induce Immune Responses to All Four Dengue Virus Serotypes",http://dx.doi.org/10.1128/CVI.00330-06,PMC1797786,,,"Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and even death. Worldwide, approximately 2.5 billion people live in dengue-infested regions with about 100 million new cases each year, although many of these infections are believed to be silent. There are four antigenically distinct serotypes of dengue virus; thus, immunity from one serotype will not cross-protect from infection with the other three. The difficulties that hamper vaccine development include requirements of the natural conformation of the envelope glycoprotein to induce neutralizing immune responses and the necessity of presenting antigens of all four serotypes. Currently, the only way to meet these requirements is to use a mixture of four serotypes of live attenuated dengue viruses, but safety remains a major problem. In this study, we have developed the basis for a tetravalent dengue vaccine using a novel complex adenovirus platform that is capable of expressing multiple antigens de novo. This dengue vaccine is constructed as a pair of vectors that each expresses the premembrane and envelope genes of two different dengue virus serotypes. Upon vaccination, the vaccine expressed high levels of the dengue virus antigens in cells to mimic a natural infection and induced both humoral and cellular immune responses against multiple serotypes of dengue virus in an animal model. Further analyses show the humoral responses were indeed neutralizing against all four serotypes. Our studies demonstrate the concept of mimicking infections to induce immune responses by synthesizing dengue virus membrane antigens de novo and the feasibility of developing an effective tetravalent dengue vaccine by vector-mediated expression of glycoproteins of the four serotypes.",,"['Holman, David H.', 'Wang, Danher', 'Raviprakash, Kanakatte', 'Raja, Nicholas U.', 'Luo, Min', 'Zhang, Jianghui', 'Porter, Kevin R.', 'Dong, John Y.']",,,,
,PMC,"Coupling Molecular Beacons to Barcoded Metal Nanowires for Multiplexed, Sealed Chamber DNA Bioassays",http://dx.doi.org/10.1021/ja0658261,PMC2849162,,,"We have combined molecular beacon (MB) probes with barcoded metal nanowires to enable no-wash, sealed chamber, multiplexed detection of nucleic acids. Probe design and experimental parameters important in nanowire-based MB assays are discussed. Loop regions of 24 bases and 5 base pair stem regions in the beacon probes gave optimal performance. Our results suggest that thermodynamic predictions for secondary structure stability of solution-phase MB can guide probe design for nanowire-based assays. Dengue virus-specific probes with predicted solution-phase ΔG of folding in 500 mM buffered NaCl of approximately −4 kcal/mol performed better than those with ΔG > −2 or < −6 kcal/mol. Buffered 300–500 mM NaCl was selected after comparison of several buffers previously reported for similar types of assays, and 200–500 mM NaCl was found to be the optimal ionic strength for the hybridization temperatures (25 and 50 °C) and probe designs used here. Target binding to the surface as a function of solution concentration fit a Sips isotherm with K(d) = 1.7 ± 0.3 nM. The detection limit was ∼100 pM, limited by incomplete quenching. Single base mismatches could be discriminated from fully complementary targets. Oligonucleotide target sequences specific for human immunodeficiency, hepatitis C, and severe acute respiratory viruses were assayed simultaneously in a no-wash, sealed chamber, multiplexed experiment in which each of three probe sequences was attached to a different pattern of encoded nanowires. Finally, we demonstrated that probe-coated nanowires retain their selectivity and sensitivity in a triplexed assay after storage for over 3 months.",,"['Stoermer, Rebecca L.', 'Cederquist, Kristin B.', 'McFarland, Sean K.', 'Sha, Michael Y.', 'Penn, Sharron G.', 'Keating, Christine D.']",,,,
,PMC,Aurintricarboxylic Acid Inhibits the Early Stage of Vaccinia Virus Replication by Targeting both Cellular and Viral Factors,http://dx.doi.org/10.1128/JVI.02531-06,PMC1865980,,,"Aurintricarboxylic acid (ATA) has been shown to inhibit the replication of viruses from several different families, including human immunodeficiency virus, vesicular stomatitis virus, and the coronavirus causing severe acute respiratory syndrome. This study characterizes the inhibitory effect of ATA on vaccinia virus replication in HeLa, Huh7, and AD293 cells. Vaccinia virus replication is significantly abrogated upon ATA treatment, which is associated with the inhibition of early viral gene transcription. This inhibitory effect may be attributed to two findings. First, ATA blocks the phosphorylation of extracellular signal-regulated kinase 1/2, an event shown to be essential for vaccinia virus replication. Second, ATA inhibits the phosphatase activity of the viral enzyme H1L, which is required to initiate viral transcription. Thus, ATA inhibits vaccinia virus replication by targeting both cellular and viral factors essential for the early stage of replication.",,"['Myskiw, Chad', 'Deschambault, Yvon', 'Jefferies, Kristel', 'He, Runtao', 'Cao, Jingxin']",,,,
,PMC,Expression patterns and action analysis of genes associated with hepatitis virus infection during rat liver regeneration,http://dx.doi.org/10.3748/wjg.v12.i47.7626,PMC4088044,,,"AIM: To study the action of hepatitis virus infection-associated genes at transcription level during liver regeneration (LR). METHODS: Hepatitis virus infection-associated genes were obtained by collecting the data from databases and retrieving the correlated articles, and their expression changes in the regenerating rat liver were detected with the rat genome 230 2.0 array. RESULTS: Eighty-eight genes were found to be associated with liver regeneration. The number of genes initially and totally expressed during initial LR [0.5-4 h after partial hepatectomy (PH)], transition from G0 to G1 (4-6 h after PH), cell proliferation (6-66 h after PH), cell differentiation and reorganization of structure-function (66-168 h after PH) was 37, 8, 48, 3 and 37, 26, 80, 57, respectively, indicating that the genes were mainly triggered at the early stage of LR (0.5-4 h after PH), and worked at different phases. These genes were classified into 5 types according to their expression similarity, namely 37 up-regulated, 9 predominantly up-regulated, 34 down-regulated, 6 predominantly down-regulated and 2 up/down-regulated genes. Their total up- and down-regulation frequencies were 359 and 149 during LR, indicating that the expression of most genes was enhanced, while the expression of a small number of genes was attenuated during LR. According to time relevance, they were classified into 12 groups (0.5 and 1 h, 2 and 4 h, 6 h, 8 and 12 h, 16 and 96 h, 18 and 24 h, 30 and 42 h, 36 and 48 h, 54 and 60 h, 66 and 72 h, 120 and 144 h, 168 h), demonstrating that the cellular physiological and biochemical activities during LR were fluctuated. According to expression changes of the genes, their expression patterns were classified into 23 types, suggesting that the cellular physiological and biochemical activities during LR were diverse and complicated. CONCLUSION: The anti-virus infection capacity of regenerating liver can be enhanced and 88 genes play an important role in LR.",,"['Su, Li-Juan', 'Ding, Guang-Wei', 'Yang, Zhi-Li', 'Zhang, Shou-Bing', 'Yang, Yu-Xiu', 'Xu, Cun-Shuan']",,,,
,PMC,GeneChip Resequencing of the Smallpox Virus Genome Can Identify Novel Strains: a Biodefense Application,http://dx.doi.org/10.1128/JCM.01848-06,PMC1829075,,,"We developed a set of seven resequencing GeneChips, based on the complete genome sequences of 24 strains of smallpox virus (variola virus), for rapid characterization of this human-pathogenic virus. Each GeneChip was designed to analyze a divergent segment of approximately 30,000 bases of the smallpox virus genome. This study includes the hybridization results of 14 smallpox virus strains. Of the 14 smallpox virus strains hybridized, only 7 had sequence information included in the design of the smallpox virus resequencing GeneChips; similar information for the remaining strains was not tiled as a reference in these GeneChips. By use of variola virus-specific primers and long-range PCR, 22 overlapping amplicons were amplified to cover nearly the complete genome and hybridized with the smallpox virus resequencing GeneChip set. These GeneChips were successful in generating nucleotide sequences for all 14 of the smallpox virus strains hybridized. Analysis of the data indicated that the GeneChip resequencing by hybridization was fast and reproducible and that the smallpox virus resequencing GeneChips could differentiate the 14 smallpox virus strains characterized. This study also suggests that high-density resequencing GeneChips have potential biodefense applications and may be used as an alternate tool for rapid identification of smallpox virus in the future.",,"['Sulaiman, Irshad M.', 'Tang, Kevin', 'Osborne, John', 'Sammons, Scott', 'Wohlhueter, Robert M.']",,,,
,PMC,Influenza Seasonality: Underlying Causes and Modeling Theories,http://dx.doi.org/10.1128/JVI.01680-06,PMC1900246,,,,,"['Lofgren, Eric', 'Fefferman, N. H.', 'Naumov, Y. N.', 'Gorski, J.', 'Naumova, E. N.']",,,,
,PMC,Mouse Hepatitis Coronavirus A59 Nucleocapsid Protein Is a Type I Interferon Antagonist,http://dx.doi.org/10.1128/JVI.01634-06,PMC1865977,,,"The recent emergence of several new coronaviruses, including the etiological cause of severe acute respiratory syndrome, has significantly increased the importance of understanding virus-host cell interactions of this virus family. We used mouse hepatitis virus (MHV) A59 as a model to gain insight into how coronaviruses affect the type I alpha/beta interferon (IFN) system. We demonstrate that MHV is resistant to type I IFN. Protein kinase R (PKR) and the alpha subunit of eukaryotic translation initiation factor are not phosphorylated in infected cells. The RNase L activity associated with 2′,5′-oligoadenylate synthetase is not activated or is blocked, since cellular RNA is not degraded. These results are consistent with lack of protein translation shutoff early following infection. We used a well-established recombinant vaccinia virus (VV)-based expression system that lacks the viral IFN antagonist E3L to screen viral genes for their ability to rescue the IFN sensitivity of the mutant. The nucleocapsid (N) gene rescued VVΔE3L from IFN sensitivity. N gene expression prevents cellular RNA degradation and partially rescues the dramatic translation shutoff characteristic of the VVΔE3L virus. However, it does not prevent PKR phosphorylation. The results indicate that the MHV N protein is a type I IFN antagonist that likely plays a role in circumventing the innate immune response.",,"['Ye, Ye', 'Hauns, Kevin', 'Langland, Jeffrey O.', 'Jacobs, Bertram L.', 'Hogue, Brenda G.']",,,,
,PMC,Exceptional Flexibility in the Sequence Requirements for Coronavirus Small Envelope Protein Function,http://dx.doi.org/10.1128/JVI.01577-06,PMC1865940,,,"The small envelope protein (E) plays a role of central importance in the assembly of coronaviruses. This was initially established by studies demonstrating that cellular expression of only E protein and the membrane protein (M) was necessary and sufficient for the generation and release of virus-like particles. To investigate the role of E protein in the whole virus, we previously generated E gene mutants of mouse hepatitis virus (MHV) that were defective in viral growth and produced aberrantly assembled virions. Surprisingly, however, we were also able to isolate a viable MHV mutant (ΔE) in which the entire E gene, as well as the nonessential upstream genes 4 and 5a, were deleted. We have now constructed an E knockout mutant that confirms that the highly defective phenotype of the ΔE mutant is due to loss of the E gene. Additionally, we have created substitution mutants in which the MHV E gene was replaced by heterologous E genes from viruses spanning all three groups of the coronavirus family. Group 2 and 3 E proteins were readily exchangeable for that of MHV. However, the E protein of a group 1 coronavirus, transmissible gastroenteritis virus, became functional in MHV only after acquisition of particular mutations. Our results show that proteins encompassing a remarkably diverse range of primary amino acid sequences can provide E protein function in MHV. These findings suggest that E protein facilitates viral assembly in a manner that does not require E protein to make sequence-specific contacts with M protein.",,"['Kuo, Lili', 'Hurst, Kelley R.', 'Masters, Paul S.']",,,,
,PMC,Long Range Cooperative Interactions Modulate Dimerization in SARS 3CL(pro),http://dx.doi.org/10.1021/bi0616302,PMC2570436,,,"Severe acute respiratory syndrome (SARS) is an infectious disease caused by the human coronavirus, SARS-CoV. The main viral protease, SARS 3CL(pro) is a validated target for the development of antiviral therapies. Since the enzyme is a homodimer and the individual monomers are inactive, two approaches are being used to develop inhibitors: enzyme activity inhibitors that target the active site and dimerization inhibitors. Dimerization inhibitors are usually targeted to the dimerization interface and need to compete with the attractive forces between subunits in order to be effective. In this paper, we show that the dimerization of SARS 3CL(pro) is also under allosteric control and that additional and energetically more favorable target sites away from the dimerization interface may also lead to subunit dissociation. We previously identified a cluster of conserved serine residues (Ser139, Ser144 and Ser147) located adjacent to the active site of 3CL(pro) that could effectively be targeted to inactivate the protease. Mutation of any of these serine residues to alanine had a debilitating effect on the catalytic activity of 3CL(pro). In particular, the mutation of Ser147, which does not make any contact with the opposing subunit and is located approximately 9Å away from the dimer interface, totally inhibited dimerization and resulted in a complete loss of enzymatic activity. The finding that residues away from the dimer interface are able to control dimerization, defines alternative targets for the design of dimerization inhibitors.",,"['Barrila, Jennifer', 'Bacha, Usman', 'Freire, Ernesto']",,,,
,PMC,What is the best control strategy for multiple infectious disease outbreaks?,http://dx.doi.org/10.1098/rspb.2006.0015,PMC2093965,,,"Effective control of infectious disease outbreaks is an important public health goal. In a number of recent studies, it has been shown how different intervention measures like travel restrictions, school closures, treatment and prophylaxis might allow us to control outbreaks of diseases, such as SARS, pandemic influenza and others. In these studies, control of a single outbreak is considered. It is, however, not clear how one should handle a situation where multiple outbreaks are likely to occur. Here, we identify the best control strategy for such a situation. We further discuss ways in which such a strategy can be implemented to achieve additional public health objectives.",,"['Handel, Andreas', 'Longini, Ira M', 'Antia, Rustom']",,,,
,PMC,Virally Activated CD8 T Cells Home to Mycobacterium bovis BCG-Induced Granulomas but Enhance Antimycobacterial Protection Only in Immunodeficient Mice,http://dx.doi.org/10.1128/IAI.00943-06,PMC1828579,,,"The effect of secondary infections on CD4 T-cell-regulated chronic granulomatous inflammation is not well understood. Here, we have investigated the effect of an acute viral infection on the cellular composition and bacterial protection in Mycobacterium bovis strain bacille Calmette-Guérin (BCG)-induced granulomas using an immunocompetent and a partially immunodeficient murine model. Acute lymphocytic choriomeningitis virus (LCMV) coinfection of C57BL/6 mice led to substantial accumulation of gamma interferon (IFN-γ)-producing LCMV-specific T cells in liver granulomas and increased local IFN-γ. Despite traffic of activated T cells that resulted in a CD8 T-cell-dominated granuloma, the BCG liver organ load was unaltered from control levels. In OT-1 T-cell-receptor (TCR) transgenic mice, ovalbumin (OVA) immunization or LCMV coinfection of BCG-infected mice induced CD8 T-cell-dominated granulomas containing large numbers of non-BCG-specific activated T cells. The higher baseline BCG organ load in this CD8 TCR transgenic animal allowed us to demonstrate that OVA immunization and LCMV coinfection increased anti-BCG protection. The bacterial load remained substantially higher than in mice with a more complete TCR repertoire. Overall, the present study suggests that peripherally activated CD8 T cells can be recruited to chronic inflammatory sites, but their contribution to protective immunity is limited to conditions of underlying immunodeficiency.",,"['Hogan, Laura H.', 'Co, Dominic O.', 'Karman, Jozsef', 'Heninger, Erika', 'Suresh, M.', 'Sandor, Matyas']",,,,
,PMC,Preliminary crystallographic analysis of avian infectious bronchitis virus main protease,http://dx.doi.org/10.1107/S1744309106052341,PMC2330114,,,"Infectious bronchitis virus (IBV) is the prototype of the genus Coronavirus. It causes a highly contagious disease which affects the respiratory, reproductive, neurological and renal systems of chickens, resulting great economic losses in the poultry industry worldwide. The coronavirus (CoV) main protease (M(pro)), which plays a pivotal role in viral gene expression and replication through a highly complex cascade involving the proteolytic processing of replicase polyproteins, is an attractive target for antiviral drug design. In this study, IBV M(pro) was overexpressed in Escherichia coli. Crystals suitable for X-ray crystallography have been obtained using microseeding techniques and belong to space group P6(1)22. X-ray diffraction data were collected in-house to 2.7 Å resolution from a single crystal. The unit-cell parameters were a = b = 119.1, c = 270.7 Å, α = β = 90, γ = 120°. Three molecules were predicted to be present in the asymmetric unit from a calculated self-rotation function.",,"['Li, Jun', 'Shen, Wei', 'Liao, Ming', 'Bartlam, Mark']",,,,
,PMC,Facile Generation of Heat Stable Antiviral and Antitoxin Single Domain Antibodies from a Semi-synthetic Llama Library,http://dx.doi.org/10.1021/ac0610053,PMC2528076,,,"Llamas possess a class of unconventional immunoglobulins that have only heavy-chains; unpaired heavy variable domains are responsible for antigen binding. These domains have previously been cloned and expressed as single domain antibodies (sdAbs); they comprise the smallest known antigen binding fragments. SdAbs have been shown to bind antigens at >90°C and to refold after being denatured. To take advantage of the remarkable properties of sdAbs we constructed a large, semi-synthetic llama sdAb library. This library facilitated the rapid selection of binders to an array of biothreat targets. We selected sdAb specific for live vaccinia virus (a smallpox virus surrogate), hen egg lysozyme, cholera toxin, ricin, and staphylococcal enterotoxin B. The selected sdAb possessed high specificity as well as enhanced thermal stability in comparison to conventional IgG and scFv antibodies. We also determined equilibrium dissociation constants as well as demonstrated the use of several anti-toxin sdAbs as effective capture and reporter molecules in sandwich assays on the Luminex instrument. The ability to rapidly select such rugged antibodies will enhance the reliability of immunoassays by extending shelf-life, and the capacity to function in hostile environments.",,"['Goldman, Ellen R.', 'Anderson, George P.', 'Liu, Jinny L.', 'Delehanty, James B.', 'Sherwood, Laura J.', 'Osborn, Lisa E.', 'Cummins, Larry B.', 'Hayhurst, Andrew']",,,,
,PMC,Multiple Controls Regulate Nucleostemin Partitioning Between Nucleolus and Nucleoplasm,http://dx.doi.org/10.1242/jcs.03292,PMC2997529,,,"Nucleostemin plays an essential role in maintaining the continuous proliferation of stem cells and cancer cells. The movement of nucleostemin between the nucleolus and the nucleoplasm provides a dynamic way to partition the nucleostemin protein between these two compartments. Here, we showed that nucleostemin contained two nucleolus-targeting regions, the basic and the GTP-binding domains, which exhibited a short and a long nucleolar retention time, respectively. In a GTP-unbound state, the nucleolus-targeting activity of nucleostemin was blocked by a mechanism that trapped its intermediate domain in the nucleoplasm. A nucleostemin-interacting protein, RSL1D1, was identified that contained a ribosomal L1-domain, co-resided with nucleostemin in the same subnucleolar compartment non-identical to the B23 and fibrillarin distributions, and displayed a longer nucleolar residence time than nucleostemin. RSL1D1 interacted with both the basic and the GTP-binding domains of nucleostemin through a non-nucleolus-targeting region. Overexpression of the nucleolus-targeting domain of RSL1D1 alone dispersed the nucleolar nucleostemin. Loss of RSL1D1 expression reduced the compartmental size and amount of nucleostemin in the nucleolus. This work reveals that the partitioning of nucleostemin employs complex mechanisms involving both nucleolar and nucleoplasmic components, and provides insight into the post-translational regulation of its activity.",,"['Meng, Lingjun', 'Yasumoto, Hiroaki', 'Tsai, Robert Y.L.']",,,,
,PMC,The Cytoplasmic Tail of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Contains a Novel Endoplasmic Reticulum Retrieval Signal That Binds COPI and Promotes Interaction with Membrane Protein,http://dx.doi.org/10.1128/JVI.02146-06,PMC1865919,,,"Like other coronaviruses, severe acute respiratory syndrome coronavirus (SARS CoV) assembles at and buds into the lumen of the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC). Accumulation of the viral envelope proteins at this compartment is a prerequisite for virus assembly. Previously, we reported the identification of a dibasic motif (KxHxx) in the cytoplasmic tail of the SARS CoV spike (S) protein that was similar to a canonical dilysine ER retrieval signal. Here we demonstrate that this motif is a novel and functional ER retrieval signal which reduced the rate of traffic of the full-length S protein through the Golgi complex. The KxHxx motif also partially retained two different reporter proteins in the ERGIC region and reduced their rates of trafficking, although the motif was less potent than the canonical dilysine signal. The dibasic motif bound the coatomer complex I (COPI) in an in vitro binding assay, suggesting that ER retrieval may contribute to the accumulation of SARS CoV S protein near the virus assembly site for interaction with other viral structural proteins. In support of this, we found that the dibasic motif on the SARS S protein was required for its localization to the ERGIC/Golgi region when coexpressed with SARS membrane (M) protein. Thus, the cycling of SARS S through the ER-Golgi system may be required for its incorporation into assembling virions in the ERGIC.",,"['McBride, Corrin E.', 'Li, Jie', 'Machamer, Carolyn E.']",,,,
,PMC,Using models to identify routes of nosocomial infection: a large hospital outbreak of SARS in Hong Kong,http://dx.doi.org/10.1098/rspb.2006.0026,PMC2197207,,,"Two factors dominated the epidemiology of severe acute respiratory syndrome (SARS) during the 2002–2003 global outbreak, namely super-spreading events (SSE) and hospital infections. Although both factors were important during the first and the largest hospital outbreak in Hong Kong, the relative importance of different routes of infection has not yet been quantified. We estimated the parameters of a novel mathematical model of hospital infection using SARS episode data. These estimates described levels of transmission between the index super-spreader, staff and patients, and were used to compare three plausible hypotheses. The broadest of the supported hypotheses ascribes the initial surge in cases to a single super-spreading individual and suggests that the per capita risk of infection to patients increased approximately one month after the start of the outbreak. Our estimate for the number of cases caused by the SSE is substantially lower than the previously reported values, which were mostly based on self-reported exposure information. This discrepancy suggests that the early identification of the index case as a super-spreader might have led to biased contact tracing, resulting in too few cases being attributed to staff-to-staff transmission. We propose that in future outbreaks of SARS or other directly transmissible respiratory pathogens, simple mathematical models could be used to validate preliminary conclusions concerning the relative importance of different routes of transmission with important implications for infection control.",,"['Kwok, Kin On', 'Leung, Gabriel M', 'Lam, Wai Yee', 'Riley, Steven']",,,,
,PMC,Time-Controlled Microfluidic Seeding in nL-Volume Droplets To                     Separate Nucleation and Growth Stages of Protein Crystallization,http://dx.doi.org/10.1002/anie.200602946,PMC1766323,,,,,"['Gerdts, Cory J.', 'Tereshko, Valentina', 'Yadav, Maneesh K.', 'Dementieva, Irina', 'Collart, Frank', 'Joachimiak, Andrzej', 'Stevens, Raymond C.', 'Kuhn, Peter', 'Kossiakoff, Anthony', 'Ismagilov, Rustem F.']",,,,
,PMC,Utility of the aged BALB/c mouse model to demonstrate prevention and control strategies for Severe Acute Respiratory Syndrome coronavirus (SARS-CoV),http://dx.doi.org/10.1016/j.vaccine.2006.11.055,PMC1847333,,,"The causative agent of Severe Acute Respiratory Syndrome (SARS) was identified as a coronavirus (CoV) following the outbreak of 2002–2003. There are currently no licensed vaccines or treatments for SARS-CoV infections. Potential prevention and control strategies that show promise in vitro must be evaluated in animal models. The aged BALB/c mouse model for SARS supports a high level of viral replication in association with clinical illness and disease that mimics SARS in the elderly. We tested two preventive strategies, vaccination and passive transfer of serum antibody, to determine the extent of protection achieved against SARS-CoV challenge in this model. These approaches were able to achieve or induce antibody titers sufficient to reduce viral load, protect from weight loss, and reduce or eliminate histopathologic changes in the lungs of aged mice. This study validates the utility of the aged BALB/c mouse model for evaluation of the efficacy of vaccines and immunoprophylaxis.",,"['Vogel, Leatrice N.', 'Roberts, Anjeanette', 'Paddock, Christopher D.', 'Genrich, Gillian L.', 'Lamirande, Elaine W.', 'Kapadia, Sagar U.', 'Rose, John K.', 'Zaki, Sherif R.', 'Subbarao, Kanta']",,,,
,PMC,Infectiousness of smallpox relative to disease age: estimates based on transmission network and incubation period,http://dx.doi.org/10.1017/S0950268806007618,PMC2870668,,,"This study investigated the infectiousness of smallpox relative to the onset of fever using a likelihood-based estimation procedure based on the observed transmission network (n=223) and on the distribution of the incubation period (n=379). Who-infected-whom information enabled us to back-calculate the infectiousness by disease age, employing a step function model for infectiousness. Frequency of secondary transmissions was highest between 3 and 6 days after onset of fever, yielding an expected daily frequency of 20·6% (95% CI 15·1–26·4) of the total number of secondary transmissions, which is consistent with previous observations. The estimated cumulative frequency suggests that 91·1% of secondary transmissions occurred up to 9 days after onset of fever. The proposed method appeared to be useful for diseases with an acute course of illness, where transmission was not hampered by depletion of susceptible contacts.",,"['NISHIURA, H.', 'EICHNER, M.']",,,,
,PMC,Quantitating the Magnitude of the Lymphocytic Choriomeningitis Virus-Specific CD8 T-Cell Response: It Is Even Bigger than We Thought,http://dx.doi.org/10.1128/JVI.01459-06,PMC1797597,,,"Measuring the magnitudes and specificities of antiviral CD8 T-cell responses is critical for understanding the dynamics and regulation of adaptive immunity. Despite many excellent studies, the accurate measurement of the total CD8 T-cell response directed against a particular infection has been hampered by an incomplete knowledge of all CD8 T-cell epitopes and also by potential contributions of bystander expansion among CD8 T cells of irrelevant specificities. Here, we use several techniques to provide a more complete accounting of the CD8 T-cell response generated upon infection of C57BL/6 mice with lymphocytic choriomeningitis virus (LCMV). Eight days following infection, we found that 85 to 95% of CD8 T cells exhibit an effector phenotype as indicated by granzyme B, 1B11, CD62L, CD11a, and CD127 expression. We demonstrate that CD8 T-cell expansion is due to cells that divide >7 times, whereas heterologous viral infections only elicited <3 divisions among bystander memory CD8 T cells. Furthermore, we found that approximately 80% of CD8 T cells in spleen were specific for ten different LCMV-derived epitopes at the peak of primary infection. These data suggest that following a single LCMV infection, effector CD8 T cells divide ≥15 times and account for at least 80%, and possibly as much as 95%, of the CD8 T-cell pool. Moreover, the response targeted a very broad array of peptide major histocompatibility complexes (MHCs), even though we examined epitopes derived from only two of the four proteins encoded by the LCMV genome and C57BL/6 mice only have two MHC class I alleles. These data illustrate the potential enormity, specificity, and breadth of CD8 T-cell responses to viral infection and demonstrate that bystander activation does not contribute to CD8 T-cell expansion.",,"['Masopust, David', 'Murali-Krishna, Kaja', 'Ahmed, Rafi']",,,,
,PMC,Participation of both Host and Virus Factors in Induction of Severe Acute Respiratory Syndrome (SARS) in F344 Rats Infected with SARS Coronavirus,http://dx.doi.org/10.1128/JVI.01967-06,PMC1797583,,,"To understand the pathogenesis and develop an animal model of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV), the Frankfurt 1 SARS-CoV isolate was passaged serially in young F344 rats. Young rats were susceptible to SARS-CoV but cleared the virus rapidly within 3 to 5 days of intranasal inoculation. After 10 serial passages, replication and virulence of SARS-CoV were increased in the respiratory tract of young rats without clinical signs. By contrast, adult rats infected with the passaged virus showed respiratory symptoms and severe pathological lesions in the lung. Levels of inflammatory cytokines in sera and lung tissues were significantly higher in adult F344 rats than in young rats. During in vivo passage of SARS-CoV, a single amino acid substitution was introduced within the binding domain of the viral spike protein recognizing angiotensin-converting enzyme 2 (ACE2), which is known as a SARS-CoV receptor. The rat-passaged virus more efficiently infected CHO cells expressing rat ACE2 than did the original isolate. These results strongly indicate that host and virus factors such as advanced age and virus adaptation are critical for the development of SARS in rats.",,"['Nagata, Noriyo', 'Iwata, Naoko', 'Hasegawa, Hideki', 'Fukushi, Shuetsu', 'Yokoyama, Masaru', 'Harashima, Ayako', 'Sato, Yuko', 'Saijo, Masayuki', 'Morikawa, Shigeru', 'Sata, Tetsutaro']",,,,
,PMC,Murine coronavirus-induced oligodendrocyte apoptosis is mediated through the activation of the Fas signaling pathway,http://dx.doi.org/10.1016/j.virol.2006.10.044,PMC1851929,,,"We previously showed that infection of rat oligodendrocytes by ultraviolet light-inactivated mouse hepatitis virus (MHV) resulted in apoptosis, suggesting that the apoptosis is triggered during cell entry. To further characterize the earliest apoptotic signaling events, here we treated cells with an antibody specific to the MHV receptor prior to and during virus infection or with an antibody specific to MHV spike protein following virus binding. Both treatments blocked virus infection and apoptosis, indicating that virus–receptor binding is necessary but not sufficient for the apoptosis induction. Furthermore, virus infection significantly increased the formation of the “death–receptor complexes” consisting of Fas, Fas-associated death domain and procaspase-8, but did not induce the complexes involving the tumor necrosis factor receptor and its associated death domain, demonstrating the specific activation of the Fas signaling pathway. Moreover, virus infection did not alter the abundance of the individual proteins of the complexes, suggesting that the activation of the Fas signaling pathway was at the post-translational level. Treatment with a Fas/Fc chimera, which blocks Fas-Fas ligand-mediated apoptosis, inhibited the formation of the complexes and blocked the activation of caspase-8 and apoptosis in MHV-infected cells. It also inhibited the release of cytochrome c from mitochondria and the activation of caspase-9. These results demonstrate that oligodendrocyte apoptosis is triggered by MHV infection during cell entry through the activation of the Fas signaling pathway.",,"['Liu, Yin', 'Zhang, Xuming']",,,,
,PMC,The role of maternal antibodies in the emergence of severe disease as a result of fragmentation,http://dx.doi.org/10.1098/rsif.2006.0189,PMC2373401,,,"Population fragmentation is a major problem for the conservation of mammalian species. Since the spread of an infectious disease is related to the intensity of contacts between individuals, fragmentation destabilizes the way the parasites circulate in their host population. Recently, Zinkernagel has proposed that a reduction in the frequency of infections by a parasite could lead to the emergence of severe forms of the disease, previously avoided because the disease was contracted early in life and attenuated by maternal antibodies. However, it is still unclear whether this change in disease expression increases the global mortality it induces because the disease becomes more severe and also less frequent. Here, we use a mathematical model to link population fragmentation with the hypothesis of Zinkernagel. Firstly, we show that there is a change in the severity of the disease during the fragmentation process, especially at a local scale, suggesting that host population fragmentation could be a widespread mechanism of disease emergence. Secondly, we show that the emergence of the severe form of the disease can lead to a significant increase in its induced mortality. Finally, we determine the types of interactions for which the fragmentation of the host population could be the most dangerous.",,"['Fouchet, David', 'Marchandeau, Stéphane', 'Bahi-Jaber, Nargès', 'Pontier, Dominique']",,,,
,PMC,An event-based model of superspreading in epidemics,http://dx.doi.org/10.1098/rspb.2006.0219,PMC2197209,,,"Many recent disease outbreaks (e.g. SARS, foot-and-mouth disease) exhibit superspreading, where relatively few individuals cause a large number of secondary cases. Epidemic models have previously treated this as a demographic phenomenon where each individual has an infectivity allocated at random from some distribution. Here, it is shown that superspreading can also be regarded as being caused by environmental variability, where superspreading events (SSEs) occur as a stochastic consequence of the complex network of interactions made by individuals. This interpretation based on SSEs is compared with data and its efficacy in evaluating epidemic control strategies is discussed.",,"['James, Alex', 'Pitchford, Jonathan W', 'Plank, Michael J']",,,,
,PMC,Induction of Neutrophil Gelatinase-Associated Lipocalin in Vascular Injury via Activation of Nuclear Factor-κB,http://dx.doi.org/10.2353/ajpath.2006.050706,PMC1762469,,,"Neutrophil gelatinase-associated lipocalin (NGAL) has recently emerged as an important modulator of cell homeostasis. Elevated plasma NGAL levels, possibly because of activation of blood leukocytes, are associated with atherosclerosis. However, little is known about induction of NGAL expression in blood vessels. Using a rat carotid artery injury model, we found that NGAL was highly induced in the intima after angioplasty but was attenuated by adenovirus-mediated expression of a dominant-negative mutant of inhibitor of nuclear factor (NF)-κB kinase β (dnIKKβ). Expression of NGAL mRNA and protein was also up-regulated in an NF-κB-dependent manner in rat and human vascular smooth muscle cells (SMCs) in response to interleukin-1β stimulation. Rat SMC-produced NGAL was present as mono- and homomeric forms in the cytosol and in a complex containing matrix metalloproteinase-9 (MMP-9) after secretion. In agreement with levels of NGAL, proteolytic activity of MMP-9 was markedly high in the intima of injured vessels and in the culture supernatant of activated intimal SMCs but was reduced in the vessels transduced with dnIKKβ. The present study reveals a previously unrecognized vascular response to an-gioplastic injury, characterized by NF-κB-dependent expression of NGAL in vascular SMCs. Further-more, SMC-produced NGAL interacts with MMP-9, a mechanism by which NGAL may modulate MMP-9 proteolytic activity in the vascular repair process.",,"['Bu, De-xiu', 'Hemdahl, Anne-Louise', 'Gabrielsen, Anders', 'Fuxe, Jonas', 'Zhu, Chaoyong', 'Eriksson, Per', 'Yan, Zhong-qun']",,,,
,PMC,Reversible Unfolding of the Severe Acute Respiratory Syndrome Coronavirus Main Protease in Guanidinium Chloride,http://dx.doi.org/10.1529/biophysj.106.091736,PMC1783898,,,"Chemical denaturant sensitivity of the dimeric main protease from severe acute respiratory syndrome (SARS) coronavirus to guanidinium chloride was examined in terms of fluorescence spectroscopy, circular dichroism, analytical ultracentrifuge, and enzyme activity change. The dimeric enzyme dissociated at guanidinium chloride concentration of <0.4 M, at which the enzymatic activity loss showed close correlation with the subunit dissociation. Further increase in guanidinium chloride induced a reversible biphasic unfolding of the enzyme. The unfolding of the C-terminal domain-truncated enzyme, on the other hand, followed a monophasic unfolding curve. Different mutants of the full-length protease (W31 and W207/W218), with tryptophanyl residue(s) mutated to phenylalanine at the C-terminal or N-terminal domain, respectively, were constructed. Unfolding curves of these mutants were monophasic but corresponded to the first and second phases of the protease, respectively. The unfolding intermediate of the protease thus represented a folded C-terminal domain but an unfolded N-terminal domain, which is enzymatically inactive due to loss of regulatory properties. The various enzyme forms were characterized in terms of hydrophobicity and size-and-shape distributions. We provide direct evidence for the functional role of C-terminal domain in stabilization of the catalytic N-terminal domain of SARS coronavirus main protease.",,"['Chang, Hui-Ping', 'Chou, Chi-Yuan', 'Chang, Gu-Gang']",,,,
,PMC,Recent news from WHO.,,PMC2627580,,,,,,,,,
,PMC,Spatial dynamics of an epidemic of severe acute respiratory syndrome in an urban area.,,PMC2627565,,,"OBJECTIVE: To map risk of exposure to severe acute respiratory syndrome (SARS) in an urban area and assess the ability of traditional interventions to control dispersion of the disease. METHODS: Data on the Beijing SARS epidemic were used to map spatial clusters of identified contacts and to estimate transmission of SARS using a model with a time-dependent transmission rate. RESULTS: The estimated transmission rate decreased dramatically from 20 to 30 April 2003. The total number of cases in the epidemic in Beijing was estimated to be 2521. Hierarchical clustering revealed that risk-exposures were widespread, but clustered in a pattern that is distinctly related to the Beijing urban ring roads. CONCLUSION: Traditional control measures can be very effective at reducing transmission of SARS. Spatial patterns of risk-exposures can inform disease surveillance, prediction and control by identifying spatial target areas on which interventions should be focused.",,"['Wang, Jinfeng', 'McMichael, Anthony J.', 'Meng, Bin', 'Becker, Niels G.', 'Han, Weiguo', 'Glass, Kathryn', 'Wu, Jilei', 'Liu, Xuhua', 'Liu, Jiyuan', 'Li, Xiaowen', 'Zheng, Xiaoying']",,,,
,PMC,Genetic Epidemiology of Acute Respiratory Distress Syndrome: Implications for Future Prevention and Treatment,http://dx.doi.org/10.1016/j.ccm.2006.07.001,PMC2703471,,,,,"Gong, Michelle Ng",,,,
,PMC,Provincial income inequality and self‐reported health status in China during 1991–7,http://dx.doi.org/10.1136/jech.2005.043539,PMC2465504,,,"BACKGROUND: The relationship between income inequality and health has been widely explored. Today there is some evidence suggesting that good health is inversely related to income inequality. After the economic reforms initiated in the early 1980s, China experienced one of the fastest‐growing income inequalities in the world. The state of China in the 1990s is focussed on and possible effects of provincial income inequality on individual health status are explored. METHODS: A multilevel regression model is used to analyse the data collected in 1991, 1993 and 1997 from nine provinces included in the China Health and Nutrition Survey. The effects of provincial Gini coefficients on self‐rated health in each year are evaluated by two logistic regressions estimating the odds ratios of reporting poor or fair health. The patterns of this effect are compared among the survey years and also among different demographic groups. RESULTS: The analyses show an independent effect of income inequality on self‐reported health after adjusting for individual and household variables. Furthermore, the effect of income distribution is not attenuated when household income and provincial gross domestic product per capita are included in the model. The results show that there is an increased risk of about 10–15% on average for fair or poor health for people living in provinces with greater income inequalities compared with provinces with modest income inequalities. CONCLUSIONS: In China, societal income inequality appears to be an important determinant of population health during 1991–7.",,"['Pei, X', 'Rodriguez, E']",,,,
,PMC,CEACAM1 in Cervical Cancer and Precursor Lesions: Association With Human Papillomavirus Infection,http://dx.doi.org/10.1369/jhc.6A6921.2006,PMC3958116,,,"Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is an adhesion molecule expressed in a wide variety of tissues including epithelial cells, leukocytes, and tumors that may establish both homotypic and heterotypic interactions. The aim of this work was to study the protein expression pattern of CEACAM1 in cervical cancer and precursor lesions in the context of human papillomavirus (HPV) infection. We used immunohistochemistry to analyze CEACAM1 expression in formalin-fixed, paraffin-embedded cervical tissues from 15 healthy women, 15 patients with low-grade squamous intraepithelial lesions (SIL), 15 patients with high-grade SIL, and 15 patients with squamous carcinomas. HPV types were identified by PCR. CEACAM1 was either undetectable (13/15) or low (2/15) in normal cervical tissues. By contrast, CEACAM1 expression was increased in high-grade SIL (10 samples staining intermediate/high and 4 samples staining low) as compared with low-grade SIL with undetectable (n=3) or low (n= 12) expression. CEACAM1 expression was undetectable or low in cervical carcinoma. Our results suggest that CEACAM1 may be an interesting progression marker in SIL and cervical cancer, in particular due to reported immunoregulatory properties.",,"['Albarran-Somoza, Benibelks', 'Franco-Topete, Ramon', 'Delgado-Rizo, Vidal', 'Cerda-Camacho, Felipe', 'Acosta-Jimenez, Lourdes', 'Lopez-Botet, Miguel', 'Daneri-Navarro, Adrian']",,,,
,PMC,Reporting ethics committee approval and patient consent by study design in five general medical journals,http://dx.doi.org/10.1136/jme.2005.015115,PMC2563342,,,"BACKGROUND: Authors are required to describe in their manuscripts ethical approval from an appropriate committee and how consent was obtained from participants when research involves human participants. OBJECTIVE: To assess the reporting of these protections for several study designs in general medical journals. DESIGN: A consecutive series of research papers published in the Annals of Internal Medicine, BMJ, JAMA, Lancet and The New England Journal of Medicine between February and May 2003 were reviewed for the reporting of ethical approval and patient consent. Ethical approval, name of approving committee, type of consent, data source and whether the study used data collected as part of a study reported elsewhere were recorded. Differences in failure to report approval and consent by study design, journal and vulnerable study population were evaluated using multivariable logistic regression. RESULTS: Ethical approval and consent were not mentioned in 31% and 47% of manuscripts, respectively. 88 (27%) papers failed to report both approval and consent. Failure to mention ethical approval or consent was significantly more likely in all study designs (except case–control and qualitative studies) than in randomised controlled trials (RCTs). Failure to mention approval was most common in the BMJ and was significantly more likely than in The New England Journal of Medicine. Failure to mention consent was most common in the BMJ and was significantly more likely than in all other journals. No significant differences in approval or consent were found when comparing studies of vulnerable and non‐vulnerable participants. CONCLUSION: The reporting of ethical approval and consent in RCTs has improved, but journals are less good at reporting this information for other study designs. Journals should publish this information for all research on human participants.",,"['Schroter, S', 'Plowman, R', 'Hutchings, A', 'Gonzalez, A']",,,,
,PMC,Human body fluid proteome analysis,http://dx.doi.org/10.1002/pmic.200600284,PMC2910092,,,"The focus of this article is to review the recent advances in proteome analysis of human body fluids, including plasma/serum, urine, cerebrospinal fluid, saliva, bronchoalveolar lavage fluid, synovial fluid, nipple aspirate fluid, tear fluid, and amniotic fluid, as well as its applications to human disease biomarker discovery. We aim to summarize the proteomics technologies currently used for global identification and quantification of body fluid proteins, and elaborate the putative biomarkers discovered for a variety of human diseases through human body fluid proteome (HBFP) analysis. Some critical concerns and perspectives in this emerging field are also discussed. With the advances made in proteomics technologies, the impact of HBFP analysis in the search for clinically relevant disease biomarkers would be realized in the future.",,"['Hu, Shen', 'Loo, Joseph A.', 'Wong, David T.']",,,,
,PMC,Rapid and Real-Time Detection of Chikungunya Virus by Reverse Transcription Loop-Mediated Isothermal Amplification Assay,http://dx.doi.org/10.1128/JCM.01734-06,PMC1829040,,,"The standardization and validation of a one-step, single-tube, accelerated, quantitative reverse transcription (RT) loop-mediated isothermal amplification (RT-LAMP) assay targeting the E1 gene for the rapid and real-time detection of Chikungunya virus (CHIKV) are reported. A linear relationship between the amount of template and time of positivity value over a range of 2 × 10(8) to 2 × 10(2) copies was obtained. The feasibility of CHIKV RT-LAMP for clinical diagnosis was validated with patient serum samples from an ongoing epidemic in Southern India. Optimal assay conditions with zero background were established for the detection of low levels of CHIKV in acute-phase patient serum samples. The comparative evaluation of the RT-LAMP assay with acute-phase patient serum samples demonstrated exceptionally higher sensitivity by correctly identifying 21 additional positive borderline cases that were missed by conventional RT-PCR (P < 0.0001) with a detection limit of 20 copies. The quantification of virus load in patient serum samples was also determined from the standard curve based on their time of positivity and was found to be in the range of 2 × 10(8) to 2 × 10(1) copies. In addition, the field applicability of the RT-LAMP assay was also demonstrated by standardizing SYBR Green I-based RT-LAMP wherein the amplification was carried out in a water bath at 63°C for 60 min, which was followed by monitoring gene amplification with the naked eye through color changes. These findings demonstrated that the RT-LAMP assay is a valuable tool for rapid, real-time detection as well as quantification of CHIKV in acute-phase serum samples without requiring any sophisticated equipment and has potential usefulness for clinical diagnosis and surveillance of CHIKV in developing countries.",,"['Parida, M. M.', 'Santhosh, S. R.', 'Dash, P. K.', 'Tripathi, N. K.', 'Lakshmi, V.', 'Mamidi, N.', 'Shrivastva, A.', 'Gupta, N.', 'Saxena, P.', 'Babu, J. Pradeep', 'Rao, P. V. Lakshmana', 'Morita, Kouichi']",,,,
,PMC,Using a Resequencing Microarray as a Multiple Respiratory Pathogen Detection Assay,http://dx.doi.org/10.1128/JCM.01870-06,PMC1829030,,,"Simultaneous testing for detection of infectious pathogens that cause similar symptoms (e.g., acute respiratory infections) is invaluable for patient treatment, outbreak prevention, and efficient use of antibiotic and antiviral agents. In addition, such testing may provide information regarding possible coinfections or induced secondary infections, such as virally induced bacterial infections. Furthermore, in many cases, detection of a pathogen requires more than genus/species-level resolution, since harmful agents (e.g., avian influenza virus) are grouped with other, relatively benign common agents, and for every pathogen, finer resolution is useful to allow tracking of the location and nature of mutations leading to strain variations. In this study, a previously developed resequencing microarray that has been demonstrated to have these capabilities was further developed to provide individual detection sensitivity ranging from 10(1) to 10(3) genomic copies for more than 26 respiratory pathogens while still retaining the ability to detect and differentiate between close genetic neighbors. In addition, the study demonstrated that this system allows unambiguous and reproducible sequence-based strain identification of the mixed pathogens. Successful proof-of-concept experiments using clinical specimens show that this approach is potentially very useful for both diagnostics and epidemic surveillance.",,"['Lin, Baochuan', 'Blaney, Kate M.', 'Malanoski, Anthony P.', 'Ligler, Adam G.', 'Schnur, Joel M.', 'Metzgar, David', 'Russell, Kevin L.', 'Stenger, David A.']",,,,
,PMC,A model for the spread and control of pandemic influenza in an isolated geographical region,http://dx.doi.org/10.1098/rsif.2006.0176,PMC2359860,,,"In the event of an influenza pandemic, the most probable way in which the virus would be introduced to an isolated geographical area is by an infected traveller. We use a mathematical model, structured on the location at which infection occurs and based on published parameters for influenza, to describe an epidemic in a community of one million people. The model is then modified to reflect a variety of control strategies based on social distancing measures, targeted antiviral treatment and antiviral prophylaxis and home quarantine, and the effectiveness of the strategies is compared. The results suggest that the only single strategy that would be successful in preventing an epidemic (with [Formula: see text](0)=2.0) is targeted antiviral treatment and prophylaxis, and that closing schools combined with either closing work places or home quarantine would only prevent such an epidemic if these strategies were combined with a modest level of antiviral coverage.",,"['Roberts, M.G', 'Baker, M', 'Jennings, L.C', 'Sertsou, G', 'Wilson, N']",,,,
,PMC,Protein Microarray Technology,http://dx.doi.org/10.1016/j.mad.2006.11.021,PMC1828913,,,"Protein chips have emerged as a promising approach for a wide variety of applications including the identification of protein-protein interactions, protein-phospholipid interactions, small molecule targets, and substrates of proteins kinases. They can also be used for clinical diagnostics and monitoring disease states. This article reviews current methods in the generation and applications of protein microarrays.",,"['Hall, David A.', 'Ptacek, Jason', 'Snyder, Michael']",,,,
,PMC,How generation intervals shape the relationship between growth rates and reproductive numbers,http://dx.doi.org/10.1098/rspb.2006.3754,PMC1766383,,,"Mathematical models of transmission have become invaluable management tools in planning for the control of emerging infectious diseases. A key variable in such models is the reproductive number R. For new emerging infectious diseases, the value of the reproductive number can only be inferred indirectly from the observed exponential epidemic growth rate r. Such inference is ambiguous as several different equations exist that relate the reproductive number to the growth rate, and it is unclear which of these equations might apply to a new infection. Here, we show that these different equations differ only with respect to their assumed shape of the generation interval distribution. Therefore, the shape of the generation interval distribution determines which equation is appropriate for inferring the reproductive number from the observed growth rate. We show that by assuming all generation intervals to be equal to the mean, we obtain an upper bound to the range of possible values that the reproductive number may attain for a given growth rate. Furthermore, we show that by taking the generation interval distribution equal to the observed distribution, it is possible to obtain an empirical estimate of the reproductive number.",,"['Wallinga, J', 'Lipsitch, M']",,,,
,PMC,Increased rainfall is associated with increased risk for legionellosis,http://dx.doi.org/10.1017/S0950268806007552,PMC2870637,,,"Legionnaires' disease (LD) is caused by Legionella species, most of which live in water. The Mid-Atlantic region experienced a sharp rise in LD in 2003 coinciding with a period of record-breaking rainfall. To investigate a possible relationship, we analysed the association between monthly legionellosis incidence and monthly rainfall totals from January 1990 to December 2003 in five Mid-Atlantic states. Using negative binomial model a 1-cm increase in rainfall was associated with a 2·6% (RR 1·026, 95% CI 1·012–1·040) increase in legionellosis incidence. The average monthly rainfall from May to September 1990–2002 was 10·4 cm compared to 15·7 cm from May to September 2003. This change in rainfall corresponds to an increased risk for legionellosis of approximately 14·6% (RR 1·146, 95% CI 1·067–1·231). Legionellosis incidence increased during periods of increased rainfall; identification of mechanisms that increase exposure and transmission of Legionella during rainfall might lead to opportunities for prevention.",,"['HICKS, L.\xa0A.', 'ROSE, C.\xa0E.', 'FIELDS, B.\xa0S.', 'DREES, M.\xa0L.', 'ENGEL, J.\xa0P.', 'JENKINS, P.\xa0R.', 'ROUSE, B.\xa0S.', 'BLYTHE, D.', 'KHALIFAH, A.\xa0P.', 'FEIKIN, D.\xa0R.', 'WHITNEY, C.\xa0G.']",,,,
,PMC,Outbreaks of Multidrug-Resistant Pseudomonas aeruginosa in Community Hospitals in Japan,http://dx.doi.org/10.1128/JCM.01772-06,PMC1829129,,,"We previously reported an outbreak in a neurosurgery ward of catheter-associated urinary tract infection with multidrug-resistant (MDR) Pseudomonas aeruginosa strain IMCJ2.S1, carrying the 6′-N-aminoglycoside acetyltransferase gene [aac(6′)-Iae]. For further epidemiologic studies, 214 clinical isolates of MDR P. aeruginosa showing resistance to imipenem (MIC ≥ 16 μg/ml), amikacin (MIC ≥ 64 μg/ml), and ciprofloxacin (MIC ≥ 4 μg/ml) were collected from 13 hospitals in the same prefecture in Japan. We also collected 70 clinical isolates of P. aeruginosa that were sensitive to one or more of these antibiotics and compared their characteristics with those of the MDR P. aeruginosa isolates. Of the 214 MDR P. aeruginosa isolates, 212 (99%) were serotype O11. We developed a loop-mediated isothermal amplification (LAMP) assay and a slide agglutination test for detection of the aac(6′)-Iae gene and the AAC(6′)-Iae protein, respectively. Of the 212 MDR P. aeruginosa isolates, 212 (100%) and 207 (98%) were positive in the LAMP assay and in the agglutination test, respectively. Mutations of gyrA and parC genes resulting in amino acid substitutions were detected in 213 of the 214 MDR P. aeruginosa isolates (99%). Of the 214 MDR P. aeruginosa isolates, 212 showed pulsed-field gel electrophoresis patterns with ≥70% similarity to that of IMCJ2.S1 and 83 showed a pattern identical to that of IMCJ2.S1, indicating that clonal expansion of MDR P. aeruginosa occurred in community hospitals in this area. The methods developed in this study to detect aac(6′)-Iae were rapid and effective in diagnosing infections caused by various MDR P. aeruginosa clones.",,"['Sekiguchi, Jun-Ichiro', 'Asagi, Tsukasa', 'Miyoshi-Akiyama, Tohru', 'Kasai, Atsushi', 'Mizuguchi, Yukie', 'Araake, Minako', 'Fujino, Tomoko', 'Kikuchi, Hideko', 'Sasaki, Satoru', 'Watari, Hajime', 'Kojima, Tadashi', 'Miki, Hiroshi', 'Kanemitsu, Keiji', 'Kunishima, Hiroyuki', 'Kikuchi, Yoshihiro', 'Kaku, Mitsuo', 'Yoshikura, Hiroshi', 'Kuratsuji, Tadatoshi', 'Kirikae, Teruo']",,,,
,PMC,Detection of Human Bocavirus in Canadian Children in a 1-Year Study,http://dx.doi.org/10.1128/JCM.01044-06,PMC1829076,,,"Human bocavirus was detected by PCR in 65 (5.1%) of 1,265 respiratory specimens collected in 2002 and 2003 from the Stollery Children's Hospital from children <17 years of age. The spectrum of illness included upper respiratory infection, croup, bronchiolitis, and pneumonia with a prominence of cough and fever.",,"['Bastien, Nathalie', 'Chui, Natalie', 'Robinson, Joan L.', 'Lee, Bonita E.', 'Dust, Kerry', 'Hart, Laura', 'Li, Yan']",,,,
,PMC,Comparative Analysis of Twelve Genomes of Three Novel Group 2c and Group 2d Coronaviruses Reveals Unique Group and Subgroup Features,http://dx.doi.org/10.1128/JVI.02182-06,PMC1797546,,,"Twelve complete genomes of three novel coronaviruses—bat coronavirus HKU4 (bat-CoV HKU4), bat-CoV HKU5 (putative group 2c), and bat-CoV HKU9 (putative group 2d)—were sequenced. Comparative genome analysis showed that the various open reading frames (ORFs) of the genomes of the three coronaviruses had significantly higher amino acid identities to those of other group 2 coronaviruses than group 1 and 3 coronaviruses. Phylogenetic trees constructed using chymotrypsin-like protease, RNA-dependent RNA polymerase, helicase, spike, and nucleocapsid all showed that the group 2a and 2b and putative group 2c and 2d coronaviruses are more closely related to each other than to group 1 and 3 coronaviruses. Unique genomic features distinguishing between these four subgroups, including the number of papain-like proteases, the presence or absence of hemagglutinin esterase, small ORFs between the membrane and nucleocapsid genes and ORFs (NS7a and NS7b), bulged stem-loop and pseudoknot structures downstream of the nucleocapsid gene, transcription regulatory sequence, and ribosomal recognition signal for the envelope gene, were also observed. This is the first time that NS7a and NS7b downstream of the nucleocapsid gene has been found in a group 2 coronavirus. The high Ka/Ks ratio of NS7a and NS7b in bat-CoV HKU9 implies that these two group 2d-specific genes are under high selective pressure and hence are rapidly evolving. The four subgroups of group 2 coronaviruses probably originated from a common ancestor. Further molecular epidemiological studies on coronaviruses in the bats of other countries, as well as in other animals, and complete genome sequencing will shed more light on coronavirus diversity and their evolutionary histories.",,"['Woo, Patrick C. Y.', 'Wang, Ming', 'Lau, Susanna K. P.', 'Xu, Huifang', 'Poon, Rosana W. S.', 'Guo, Rongtong', 'Wong, Beatrice H. L.', 'Gao, Kai', 'Tsoi, Hoi-wah', 'Huang, Yi', 'Li, Kenneth S. M.', 'Lam, Carol S. F.', 'Chan, Kwok-hung', 'Zheng, Bo-jian', 'Yuen, Kwok-yung']",,,,
,PMC,Prospective comparison of three predictive rules for assessing severity of community‐acquired pneumonia in Hong Kong,http://dx.doi.org/10.1136/thx.2006.069740,PMC2092476,,,"BACKGROUND: Community‐acquired pneumonia (CAP) is a leading infectious cause of death throughout the world, including Hong Kong. AIM: To compare the ability of three validated prediction rules for CAP to predict mortality in Hong Kong: the 20 variable Pneumonia Severity Index (PSI), the 6‐point CURB65 scale adopted by the British Thoracic Society and the simpler CRB65. METHODS: A prospective observational study of 1016 consecutive inpatients with CAP (583 men, mean (SD) age 72 (17) years) was performed in a university hospital in the New Territories of Hong Kong in 2004. The patients were classified into three risk groups (low, intermediate and high) according to each rule. The ability of the three rules to predict 30 day mortality was compared. RESULTS: The overall mortality and intensive care unit (ICU) admission rates were 8.6% and 4.0%, respectively. PSI, CURB65 and CRB65 performed similarly, and the areas under the receiver operating characteristic (ROC) curve were 0.736 (95% CI 0.687 to 0.736), 0.733 (95% CI 0.679 to 0.787) and 0.694 (95% CI 0.634 to 0.753), respectively. All three rules had high negative predictive values but relatively low positive predictive values at all cut‐off points. Larger proportions of patients were identified as low risk by PSI (47.2%) and CURB65 (43.3%) than by CRB65 (12.6%). CONCLUSION: All three predictive rules have a similar performance in predicting the severity of CAP, but CURB65 is more suitable than the other two for use in the emergency department because of its simplicity of application and ability to identify low‐risk patients.",,"['Man, Shin Yan', 'Lee, Nelson', 'Ip, Margaret', 'Antonio, Gregory E', 'Chau, Shirley SL', 'Mak, Paulina', 'Graham, Colin A', 'Zhang, Mingdong', 'Lui, Grace', 'Chan, Paul K S', 'Ahuja, Anil T', 'Hui, David S', 'Sung, Joseph J Y', 'Rainer, Timothy H']",,,,
,PMC,Who's using whom?,http://dx.doi.org/10.1136/bmj.39034.630926.DB,PMC1647359,,,Will China gain influence from having one of its people at the head of WHO or will the winner be WHO itself as China becomes more engaged in fighting infectious disease? Anne Glusker reports,,"Glusker, Anne",,,,
,PMC,Naturally Occurring Anti-Escherichia coli Protein Antibodies in the Sera of Healthy Humans Cause Analytical Interference in a Recombinant Nucleocapsid Protein-Based Enzyme-Linked Immunosorbent Assay for Serodiagnosis of Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1128/CVI.00136-06,PMC1797702,,,We reported the analytical interference of anti-Escherichia coli protein (EP) antibodies in human sera and residual EP in a recombinant nucleocapsid protein-based enzyme-linked immunosorbent assay as a possible source of false positives in severe acute respiratory syndrome serodiagnosis. The rate of false positives was significantly reduced by adding mouse anti-EP antiserum in the blocking step.,,"['Yip, Chi Wai', 'Hon, Chung Chau', 'Zeng, Fanya', 'Chow, Ken Y. C.', 'Chan, Kwok Hung', 'Peiris, Joseph S. M.', 'Leung, Frederick C. C.']",,,,
,PMC,Detection of Coccidioides Species in Clinical Specimens by Real-Time PCR,http://dx.doi.org/10.1128/JCM.01776-06,PMC1828991,,,"Coccidioides spp. are dimorphic fungal pathogens endemic to the semiarid regions of North, Central, and South America. Currently, direct smear and culture are the most common means of identifying Coccidioides spp. While these methods offer relatively sensitive and specific means of detecting Coccidioides spp., growth in culture may take up to 3 weeks, potentially delaying the diagnosis and initiation of appropriate antifungal therapy. In addition, growth of the organism represents a significant safety risk to laboratory personnel. The need for a rapid and safe means of diagnosing coccidioidomycosis prompted us to develop a real-time PCR assay to detect Coccidioides spp. directly from clinical specimens. Primers and fluorescent resonance energy transfer (FRET) probes were designed to target the internal transcribed spacer 2 region of Coccidioides. The assay's limit of detection is below 50 targets per reaction. An analysis of 40 Coccidioides sp. clinical isolates grown in culture demonstrated 100% sensitivity of the assay. A cross-reactivity panel containing fungi, bacteria, mycobacteria, and viruses was tested and demonstrated 100% specificity for Coccidioides spp. An analysis of 266 respiratory specimens by LightCycler PCR demonstrated 100% sensitivity and 98.4% specificity for Coccidioides spp. compared with culture. Analysis of 66 fresh tissue specimens yielded 92.9% sensitivity and 98.1% specificity versus those of the culture method. The sensitivity of the assay testing 148 paraffin-embedded tissue samples is 73.4%. A rapid method for the detection of Coccidioides spp. directly from clinical material will greatly assist in the timely diagnosis and treatment of patients, while at the same time decreasing the risk of accidental exposure to laboratory personnel.",,"['Binnicker, M. J.', 'Buckwalter, S. P.', 'Eisberner, J. J.', 'Stewart, R. A.', 'McCullough, A. E.', 'Wohlfiel, S. L.', 'Wengenack, N. L.']",,,,
,PMC,A Severe Acute Respiratory Syndrome Coronavirus That Lacks the E Gene Is Attenuated In Vitro and In Vivo,http://dx.doi.org/10.1128/JVI.01467-06,PMC1797558,,,"A deletion mutant of severe acute respiratory syndrome coronavirus (SARS-CoV) has been engineered by deleting the structural E gene in an infectious cDNA clone that was constructed as a bacterial artificial chromosome (BAC). The recombinant virus lacking the E gene (rSARS-CoV-ΔE) was rescued in Vero E6 cells. The recovered deletion mutant grew in Vero E6, Huh-7, and CaCo-2 cells to titers 20-, 200-, and 200-fold lower than the recombinant wild-type virus, respectively, indicating that although the E protein has an effect on growth, it is not essential for virus replication. No differences in virion stability under a wide range of pH and temperature were detected between the deletion mutant and recombinant wild-type viruses. Although both viruses showed the same morphology by electron microscopy, the process of morphogenesis seemed to be less efficient with the defective virus than with the recombinant wild-type one. The rSARS-CoV-ΔE virus replicated to titers 100- to 1,000-fold lower than the recombinant wild-type virus in the upper and lower respiratory tract of hamsters, and the lower viral load was accompanied by less inflammation in the lungs of hamsters infected with rSARS-CoV-ΔE virus than with the recombinant wild-type virus. Therefore, the SARS-CoV that lacks the E gene is attenuated in hamsters, might be a safer research tool, and may be a good candidate for the development of a live attenuated SARS-CoV vaccine.",,"['DeDiego, Marta L.', 'Álvarez, Enrique', 'Almazán, Fernando', 'Rejas, María Teresa', 'Lamirande, Elaine', 'Roberts, Anjeanette', 'Shieh, Wun-Ju', 'Zaki, Sherif R.', 'Subbarao, Kanta', 'Enjuanes, Luis']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Infection of Mice Transgenic for the Human Angiotensin-Converting Enzyme 2 Virus Receptor,http://dx.doi.org/10.1128/JVI.01702-06,PMC1797529,,,"Animal models for severe acute respiratory syndrome (SARS) coronavirus infection of humans are needed to elucidate SARS pathogenesis and develop vaccines and antivirals. We developed transgenic mice expressing human angiotensin-converting enzyme 2, a functional receptor for the virus, under the regulation of a global promoter. A transgenic lineage, designated AC70, was among the best characterized against SARS coronavirus infection, showing weight loss and other clinical manifestations before reaching 100% mortality within 8 days after intranasal infection. High virus titers were detected in the lungs and brains of transgene-positive (Tg(+)) mice on days 1 and 3 after infection. Inflammatory mediators were also detected in these tissues, coinciding with high levels of virus replication. Lower virus titers were also detected in other tissues, including blood. In contrast, infected transgene-negative (Tg(−)) mice survived without showing any clinical illness. Pathologic examination suggests that the extensive involvement of the central nervous system likely contributed to the death of Tg(+) mice, even though viral pneumonia was present. Preliminary studies with mice of a second lineage, AC63, in which the transgene expression was considerably less abundant than that in the AC70 line, revealed that virus replication was largely restricted to the lungs but not the brain. Importantly, despite significant weight loss, infected Tg(+) AC63 mice eventually recovered from the illness without any mortality. The severity of the disease that developed in these transgenic mice—AC70 in particular—makes these mouse models valuable not only for evaluating the efficacy of antivirals and vaccines, but also for studying SARS coronavirus pathogenesis.",,"['Tseng, Chien-Te K.', 'Huang, Cheng', 'Newman, Patrick', 'Wang, Nan', 'Narayanan, Krishna', 'Watts, Douglas M.', 'Makino, Shinji', 'Packard, Michelle M.', 'Zaki, Sherif R.', 'Chan, Teh-sheng', 'Peters, Clarence J.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Protein 6 Accelerates Murine Coronavirus Infections,http://dx.doi.org/10.1128/JVI.01515-06,PMC1797517,,,"One or more of the unique 3′-proximal open reading frames (ORFs) of the severe acute respiratory syndrome (SARS) coronavirus may encode determinants of virus virulence. A prime candidate is ORF6, which encodes a 63-amino-acid membrane-associated peptide that can dramatically increase the lethality of an otherwise attenuated JHM strain of murine coronavirus (L. Pewe, H. Zhou, J. Netland, C. Tangudu, H. Olivares, L. Shi, D. Look, T. Gallagher, and S. Perlman, J. Virol. 79:11335-11342, 2005). To discern virulence mechanisms, we compared the in vitro growth properties of rJ.6, a recombinant JHM expressing the SARS peptide, with isogenic rJ.6-KO, which has an inactive ORF containing a mutated initiation codon and a termination codon at internal position 27. The rJ.6 infections proceeded rapidly, secreting progeny about 1.5 h earlier than rJ.6-KO infections did. The rJ.6 infections were also set apart by early viral protein accumulation and by robust expansion via syncytia, a characteristic feature of JHM virus dissemination. We found no evidence for protein 6 operating at the virus entry or assembly stage, as virions from either infection were indistinguishable. Rather, protein 6 appeared to operate by fostering viral RNA and protein synthesis, as RNA quantifications by reverse transcription-quantitative PCR revealed viral RNA levels in the rJ.6 cultures that were five to eight times higher than those lacking protein 6. Furthermore, protein 6 coimmunoprecipitated with viral RNAs and colocalized on cytoplasmic vesicles with replicating viral RNAs. The SARS coronavirus encodes a novel membrane protein 6 that can accelerate replication of a related mouse virus, a property that may explain its ability to increase in vivo virus virulence.",,"['Tangudu, Chandra', 'Olivares, Heidi', 'Netland, Jason', 'Perlman, Stanley', 'Gallagher, Thomas']",,,,
,PMC,"Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame (ORF) 3b, ORF 6, and Nucleocapsid Proteins Function as Interferon Antagonists",http://dx.doi.org/10.1128/JVI.01782-06,PMC1797484,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) is highly pathogenic in humans, with a death rate near 10%. This high pathogenicity suggests that SARS-CoV has developed mechanisms to overcome the host innate immune response. It has now been determined that SARS-CoV open reading frame (ORF) 3b, ORF 6, and N proteins antagonize interferon, a key component of the innate immune response. All three proteins inhibit the expression of beta interferon (IFN-β), and further examination revealed that these SARS-CoV proteins inhibit a key protein necessary for the expression of IFN-β, IRF-3. N protein dramatically inhibited expression from an NF-κB-responsive promoter. All three proteins were able to inhibit expression from an interferon-stimulated response element (ISRE) promoter after infection with Sendai virus, while only ORF 3b and ORF 6 proteins were able to inhibit expression from the ISRE promoter after treatment with interferon. This indicates that N protein inhibits only the synthesis of interferon, while ORF 3b and ORF 6 proteins inhibit both interferon synthesis and signaling. ORF 6 protein, but not ORF 3b or N protein, inhibited nuclear translocation but not phosphorylation of STAT1. Thus, it appears that these three interferon antagonists of SARS-CoV inhibit the interferon response by different mechanisms.",,"['Kopecky-Bromberg, Sarah A.', 'Martínez-Sobrido, Luis', 'Frieman, Matthew', 'Baric, Ralph A.', 'Palese, Peter']",,,,
,PMC,"Expression, purification and characterization of recombinant severe acute respiratory syndrome coronavirus non-structural protein 1",http://dx.doi.org/10.1016/j.pep.2006.11.005,PMC1862784,,,"The coronavirus (CoV) responsible for severe acute respiratory syndrome (SARS), SARS-CoV, encodes two large polyproteins (pp1a and pp1ab) that are processed by two viral proteases to yield mature non-structural proteins (nsps). Many of these nsps have essential roles in viral replication, but several have no assigned function and possess amino acid sequences that are unique to the CoV family. One such protein is SARS-CoV nsp1, which is processed from the N-terminus of both pp1a and pp1ab. The mature SARS-CoV protein is present in cells several hours post-infection and co-localizes to the viral replication complex, but its function in the viral life cycle remains unknown. Furthermore, nsp1 sequences are highly divergent across the CoV family, and it has been suggested that this is due to nsp1 possessing a function specific to viral interactions with its host cell or acting as a host specific virulence factor. In order to initiate structural and biophysical studies of SARS-CoV nsp1, a recombinant expression system and a purification protocol have been developed, yielding milligram quantities of highly purified SARS-CoV nsp1. The purified protein was characterized using circular dichroism, size exclusion chromatography, and multi-angle light scattering.",,"['Brucz, Kimberly', 'Miknis, Zachary J.', 'Schultz, L. Wayne', 'Umland, Timothy C.']",,,,
,PMC,Neurovirulence Properties of Recombinant Vesicular Stomatitis Virus Vectors in Non-Human Primates,http://dx.doi.org/10.1016/j.virol.2006.10.026,PMC1865117,,,"Although vesicular stomatitis virus (VSV) neurovirulence and pathogenicity in rodents have been well studied, little is known about VSV pathogenicity in non-human primates. To address this question, we measured VSV viremia, shedding, and neurovirulence in macaques. Following intranasal inoculation, macaques shed minimal recombinant VSV (rVSV) in nasal washes for one day post-inoculation; viremia was not detected. Following intranasal inoculation of macaques, wild type (wt) VSV, rVSV, and two rVSV-HIV vectors showed no evidence of spread to CNS tissues. However, macaques inoculated intrathalamically with wt VSV developed severe neurological disease. One of four macaques receiving rVSV developed clinical and histological signs similar to the wt group, while the remaining three macaques in this group and all of the macaques in the rVSV-HIV vector groups showed no clinical signs of disease and reduced severity of histopathology compared to the wt group. The implications of these findings for rVSV vaccine development are discussed.",,"['Johnson, J. Erik', 'Nasar, Farooq', 'Coleman, John W.', 'Price, Roger E.', 'Javadian, Ali', 'Draper, Kenneth', 'Lee, Margaret', 'Reilly, Patricia A.', 'Clarke, David K.', 'Hendry, R. Michael', 'Udem, Stephen A.']",,,,
,PMC,ROLE OF RESPIRATORY SYNCYTIAL VIRUS IN ACUTE OTITIS MEDIA: IMPLICATIONS FOR VACCINE DEVELOPMENT,http://dx.doi.org/10.1016/j.vaccine.2006.10.045,PMC1828634,,,"We summarize herein the results of various virologic studies of acute otitis media (AOM) conducted at our site over a ten -year period. Among 566 children with AOM, respiratory syncytial virus (RSV) was the most common virus identified in either middle ear fluid or nasal wash; it was found in 16% of all children and 38% of virus-positive children. Seventy-one percent of the children with RSV were one year of age or older, which was significantly older than all other viruses combined (P = 0.045). RSV infection was associated with the common bacterial pathogens causing AOM. Past efforts to develop vaccines for RSV have emphasized prevention of lower respiratory tract infection in infants, which is a more serious problem but less common than AOM. Our results suggest that RSV vaccines that work only against infection in older children may have value in preventing AOM, the most common pediatric disease.",,"['Patel, Janak A.', 'Nguyen, Dang T.', 'Revai, Krystal', 'Chonmaitree, Tasnee']",,,,
,PMC,Phase 1 Safety and Immunogenicity Evaluation of a Multiclade HIV-1 DNA Candidate Vaccine,http://dx.doi.org/10.1086/509259,PMC2428069,,,"BACKGROUND: Gene-based vaccine delivery is an important strategy in the development of a preventive vaccine for acquired immunodeficiency syndrome (AIDS). Vaccine Research Center (VRC) 004 is the first phase 1 dose-escalation study of a multiclade HIV-1 DNA vaccine. METHODS: VRC-HIVDNA009-00-VP is a 4-plasmid mixture encoding subtype B Gag-Pol-Nef fusion protein and modified envelope (Env) constructs from subtypes A, B, and C. Fifty healthy, uninfected adults were randomized to receive either placebo (n = 10) or study vaccine at 2 mg (n = 5), 4 mg (n = 20), or 8 mg (n = 15) by needle-free intramuscular injection. Humoral responses (measured by enzyme-linked immunosorbant assay, Western blotting, and neutralization assay) and T cell responses (measured by enzyme-linked immunospot assay and intracellular cytokine staining after stimulation with antigen-specific peptide pools) were measured. RESULTS: The vaccine was well tolerated and induced cellular and humoral responses. The maximal CD4(+) and CD8(+) T cell responses occurred after 3 injections and were in response to Env peptide pools. The pattern of cytokine expression by vaccine-induced HIV-specific T cells evolved over time, with a diminished frequency of interferon-γ–producing T cells and an increased frequency of interleukin-2–producing T cells at 1 year. CONCLUSIONS: DNA vaccination induced antibody to and T cell responses against 3 major HIV-1 subtypes and will be further evaluated as a potential component of a preventive AIDS vaccine regimen.",,"['Graham, Barney S.', 'Koup, Richard A.', 'Roederer, Mario', 'Bailer, Robert T.', 'Enama, Mary E.', 'Moodie, Zoe', 'Martin, Julie E.', 'McCluskey, Margaret M.', 'Chakrabarti, Bimal K.', 'Lamoreaux, Laurie', 'Andrews, Charla A.', 'Gomez, Phillip L.', 'Mascola, John R.', 'Nabel, Gary J.', None]",,,,
,PMC,"Mutational Analysis of Aminopeptidase N, a Receptor for Several Group 1 Coronaviruses, Identifies Key Determinants of Viral Host Range",http://dx.doi.org/10.1128/JVI.01510-06,PMC1797531,,,"Feline coronavirus (FCoV), porcine transmissible gastroenteritis coronavirus (TGEV), canine coronavirus (CCoV), and human coronavirus HCoV-229E, which belong to the group 1 coronavirus, use aminopeptidase N (APN) of their natural host and feline APN (fAPN) as receptors. Using mouse-feline APN chimeras, we identified three small, discontinuous regions, amino acids (aa) 288 to 290, aa 732 to 746 (called R1), and aa 764 to 788 (called R2) in fAPN that determined the host ranges of these coronaviruses. Blockade of infection with anti-fAPN monoclonal antibody RG4 suggested that these three regions lie close together on the fAPN surface. Different residues in fAPN were required for infection with each coronavirus. HCoV-229E infection was blocked by an N-glycosylation sequon present between aa 288 to 290 in murine APN. TGEV required R1 of fAPN, while FCoV and CCoV required both R1 and R2 for entry. N740 and T742 in fAPN and the homologous R741 in human APN (hAPN) were key determinants of host range for FCoV, TGEV, and CCoV. Residue N740 in fAPN was essential only for CCoV receptor activity. A conservative T742V substitution or a T742R substitution in fAPN destroyed receptor activity for the pig, dog, and cat coronaviruses, while a T742S substitution retained these receptor activities. Thus, the hydroxyl on T742 is required for the coronavirus receptor activity of fAPN. In hAPN an R741T substitution caused a gain of receptor activity for TGEV but not for FCoV or CCoV. Therefore, entry and host range of these group 1 coronaviruses depend on the ability of the viral spike glycoproteins to recognize small, species-specific amino acid differences in the APN proteins of different species.",,"['Tusell, Sonia M.', 'Schittone, Stephanie A.', 'Holmes, Kathryn V.']",,,,
,PMC,A Hypervariable Region within the 3′ cis-Acting Element of the Murine Coronavirus Genome Is Nonessential for RNA Synthesis but Affects Pathogenesis,http://dx.doi.org/10.1128/JVI.00803-06,PMC1797510,,,"The 3′ cis-acting element for mouse hepatitis virus (MHV) RNA synthesis resides entirely within the 301-nucleotide 3′ untranslated region (3′ UTR) of the viral genome and consists of three regions. Encompassing the upstream end of the 3′ UTR are a bulged stem-loop and an overlapping RNA pseudoknot, both of which are essential to MHV and common to all group 2 coronaviruses. At the downstream end of the genome is the minimal signal for initiation of negative-strand RNA synthesis. Between these two ends is a hypervariable region (HVR) that is only poorly conserved between MHV and other group 2 coronaviruses. Paradoxically, buried within the HVR is an octanucleotide motif (oct), 5′-GGAAGAGC-3′, which is almost universally conserved in coronaviruses and is therefore assumed to have a critical biological function. We conducted an extensive mutational analysis of the HVR. Surprisingly, this region tolerated numerous deletions, rearrangements, and point mutations. Most striking, a mutant deleted of the entire HVR was only minimally impaired in tissue culture relative to the wild type. By contrast, the HVR deletion mutant was highly attenuated in mice, causing no signs of clinical disease and minimal weight loss compared to wild-type virus. Correspondingly, replication of the HVR deletion mutant in the brains of mice was greatly reduced compared to that of the wild type. Our results show that neither the HVR nor oct is essential for the basic mechanism of MHV RNA synthesis in tissue culture. However, the HVR appears to play a significant role in viral pathogenesis.",,"['Goebel, Scott J.', 'Miller, Timothy B.', 'Bennett, Corey J.', 'Bernard, Kristen A.', 'Masters, Paul S.']",,,,
,PMC,Refolding of a paramyxovirus F protein from prefusion to postfusion conformations observed by liposome binding and electron microscopy,http://dx.doi.org/10.1073/pnas.0608678103,PMC1635158,,,"For paramyxoviruses, two viral glycoproteins are key to the entry process: an attachment protein (HN, H, or G) and the fusion protein (F). The F protein folds to a metastable state that can be triggered to undergo large conformational rearrangements to a fusogenic intermediate and a more stable postfusion state. The triggering mechanism that controls paramyxovirus fusion has not been elucidated. To correlate the molecular structure of a soluble form of the prefusion F (PIV5 F-GCNt) with the biological function of F, soluble F protein was triggered to refold. In the absence of HN, heat was found to function as a surrogate F trigger, and F associated with liposomes and aggregated on sucrose density gradients. Electron microscopy data showed that triggered F formed rosettes. Taken together these data suggest that release and membrane insertion of the hydrophobic fusion peptide require both cleavage of F and heat. Heating of cleaved F causes conversion to a postfusion form as judged by its “golf tee” morphology in the electron microscope. Heating of uncleaved F also causes conversion of F to a morphologically similar form. The reactivity of the F protein with conformation-specific mAbs and peptide binding suggest that soluble F-GCNt and membrane-bound F proteins refold through a comparable pathway.",,"['Connolly, Sarah A.', 'Leser, George P.', 'Yin, Hsien-Shen', 'Jardetzky, Theodore S.', 'Lamb, Robert A.']",,,,
,PMC,"Household transmission of SARS, 2003",http://dx.doi.org/10.1503/cmaj.050876,PMC1626520,,,"BACKGROUND: In the 2003 outbreak in Toronto (in Ontario, Canada) of severe acute respiratory syndrome (SARS), about 20% of cases resulted from household transmission. The purpose of our study was to determine characteristics associated with the transmission of SARS within households. METHODS: A retrospective cohort of SARS-affected households was studied to determine risk factors for household transmission. Questionnaires addressed characteristics of the index case, the household and behaviours among household members. Potential risk factors for secondary transmission of infection were assessed in regression models appropriate to the outcome (secondary cases) and nonindependence of household members. RESULTS: The 74 households that participated included 18 secondary cases and 158 uninfected household members in addition to the 74 index cases. The household secondary attack rate was 10.2% (95% confidence interval [CI] 6.7%–23.5%). There was a linear association between the time the index patient spent at home after symptom onset and the secondary attack rate. Infected health care workers who were index cases had lower rates of household transmission. INTERPRETATION: SARS transmission in households is complex and increases with the length of time an ill person spends at home. Risk of transmission was lower when the index case was a health care worker. Rapid case identification is the public health measure most useful in minimizing exposure in the home.",,"['Wilson-Clark, Samantha D.', 'Deeks, Shelley L.', 'Gournis, Effie', 'Hay, Karen', 'Bondy, Susan', 'Kennedy, Erin', 'Johnson, Ian', 'Rea, Elizabeth', 'Kuschak, Theodore', 'Green, Diane', 'Abbas, Zahid', 'Guarda, Brenda']",,,,
,PMC,Highlights of this issue,,PMC1626506,,,,,,,,,
,PMC,Database of traditional Chinese medicine and its application to studies of mechanism and to prescription validation,http://dx.doi.org/10.1038/sj.bjp.0706945,PMC2014641,,,"BACKGROUND AND PURPOSE: Traditional Chinese Medicine (TCM) is widely practised and is viewed as an attractive alternative to conventional medicine. Quantitative information about TCM prescriptions, constituent herbs and herbal ingredients is necessary for studying and exploring TCM. EXPERIMENTAL APPROACH: We manually collected information on TCM in books and other printed sources in Medline. The Traditional Chinese Medicine Information Database TCM-ID, at http://tcm.cz3.nus.edu.sg/group/tcm-id/tcmid.asp, was introduced for providing comprehensive information about all aspects of TCM including prescriptions, constituent herbs, herbal ingredients, molecular structure and functional properties of active ingredients, therapeutic and side effects, clinical indication and application and related matters. RESULTS: TCM-ID currently contains information for 1,588 prescriptions, 1,313 herbs, 5,669 herbal ingredients, and the 3D structure of 3,725 herbal ingredients. The value of the data in TCM-ID was illustrated by using some of the data for an in-silico study of molecular mechanism of the therapeutic effects of herbal ingredients and for developing a computer program to validate TCM multi-herb preparations. CONCLUSIONS AND IMPLICATIONS: The development of systems biology has led to a new design principle for therapeutic intervention strategy, the concept of ‘magic shrapnel' (rather than the ‘magic bullet'), involving many drugs against multiple targets, administered in a single treatment. TCM offers an extensive source of examples of this concept in which several active ingredients in one prescription are aimed at numerous targets and work together to provide therapeutic benefit. The database and its mining applications described here represent early efforts toward exploring TCM for new theories in drug discovery.",,"['Chen, X', 'Zhou, H', 'Liu, Y B', 'Wang, J F', 'Li, H', 'Ung, C Y', 'Han, L Y', 'Cao, Z W', 'Chen, Y Z']",,,,
,PMC,Who will lead WHO?,,PMC1633806,,,"Deals and politicking characterise the contest for a new director general of WHO, says Anne Glusker¶",,"Glusker, Anne",,,,
,PMC,Learning from Mistakes,,PMC2095097,,,,,"Nicolle, LE",,,,
,PMC,An Outbreak of Human Coronavirus OC43 Infection and Serological Cross-reactivity with SARS Coronavirus,,PMC2095096,,,"BACKGROUND: In summer 2003, a respiratory outbreak was investigated in British Columbia, during which nucleic acid tests and serology unexpectedly indicated reactivity for severe acute respiratory syndrome coronavirus (SARS-CoV). METHODS: Cases at a care facility were epidemiologically characterized and sequentially investigated for conventional agents of respiratory infection, SARS-CoV and other human CoVs. Serological cross-reactivity between SARS-CoV and human CoV-OC43 (HCoV-OC43) was investigated by peptide spot assay. RESULTS: Ninety-five of 142 residents (67%) and 53 of 160 staff members (33%) experienced symptoms of respiratory infection. Symptomatic residents experienced cough (66%), fever (21%) and pneumonia (12%). Eight residents died, six with pneumonia. No staff members developed pneumonia. Findings on reverse transcriptase-polymerase chain reaction assays for SARS-CoV at a national reference laboratory were suspected to represent false positives, but this was confounded by concurrent identification of antibody to N protein on serology. Subsequent testing by reverse transcriptase-polymerase chain reaction confirmed HCoV-OC43 infection. Convalescent serology ruled out SARS. Notably, sera demonstrated cross-reactivity against nucleocapsid peptide sequences common to HCoV-OC43 and SARS-CoV. CONCLUSIONS: These findings underscore the virulence of human CoV-OC43 in elderly populations and confirm that cross-reactivity to antibody against nucleocapsid proteins from these viruses must be considered when interpreting serological tests for SARS-CoV.",,"['Patrick, David M', 'Petric, Martin', 'Skowronski, Danuta M', 'Guasparini, Roland', 'Booth, Timothy F', 'Krajden, Mel', 'McGeer, Patrick', 'Bastien, Nathalie', 'Gustafson, Larry', 'Dubord, Janet', 'MacDonald, Diane', 'David, Samara T', 'Srour, Leila F', 'Parker, Robert', 'Andonov, Anton', 'Isaac-Renton, Judith', 'Loewen, Nadine', 'McNabb, Gail', 'McNabb, Alan', 'Goh, Swee-Han', 'Henwick, Scott', 'Astell, Caroline', 'Guo, Jian Ping', 'Drebot, Michael', 'Tellier, Raymond', 'Plummer, Francis', 'Brunham, Robert C']",,,,
,PMC,A Process Evaluation of an Intervention to Improve Respiratory Infection Control Practices in Family Physician Offices,http://dx.doi.org/10.1007/BF03405231,PMC6976243,,,"OBJECTIVE: To conduct a process evaluation of a short-term intervention by public nurses for physicians to facilitate the incorporation of new respiratory infection control practices in physicians’ offices. DESIGN: Process evaluation. SETTING: Family physician offices in Ottawa, Ontario, Canada. PARTICIPANTS: Five public health nurse-facilitators and 53 primary care practices including 143 family physicians. METHOD: Effectiveness of facilitator training assessed by self-administered questionnaires. Data assessing process of facilitation collected through activity logs and narrative reports. Physicians’ satisfaction assessed by post-intervention questionnaire. MAIN FINDINGS: Facilitators reported that training strongly contributed to their knowledge and skills and all were either satisfied or highly satisfied with their facilitation training. All practices received at least two visits by the facilitator and more than half (51%) were visited three or more times. Facilitators identified the provision of the evidence-based Tool Kit and consensus-building with office staff as key factors contributing to the intervention’s success. Of the 45% of physicians who completed the questionnaire (65/143), only 5% reported being somewhat dissatisfied with the intervention, 11% reported the visits were not frequent enough, and 9% thought the visits were too close together. The majority (97%) felt the facilitation program should be available to all family physicians and 98% would continue to use the service if available. CONCLUSIONS: It is feasible for public health nurses to be trained in outreach facilitation to improve respiratory infection control practices in physicians’ offices and this has been widely appreciated by physicians. This model of public health/primary care collaboration deserves further exploration.",,"['Huston, Patricia', 'Hogg, William', 'Martin, Carmel', 'Soto, Enrique', 'Newbury, Adriana']",,,,
,PMC,Proceedings of the Australasian Association of Clinical Biochemists’ 44th Annual Scientific Conference,,PMC1784010,,,,,,,,,
,PMC,Skin cancer and surgical margins for basal cell carcinoma,http://dx.doi.org/10.7861/clinmedicine.6-6-622a,PMC4952783,,,,,"Varma, Sandeep",,,,
,PMC,"Skin cancer: prevalence, prevention and treatment",http://dx.doi.org/10.7861/clinmedicine.6-6-622,PMC4952782,,,,,"Telfer, Nicholas R",,,,
,PMC,Current clinical uses of intravenous immunoglobulin,http://dx.doi.org/10.7861/clinmedicine.6-6-621,PMC4952781,,,,,"['Shimoni, Zvi', 'Bulvik, Shlomo', 'Niven, Mark']",,,,
,PMC,Pandemic Threats and the Need for New Emergency Public Health Legislation in Canada,,PMC2585432,,,"The 2003 outbreak of Severe Acute Respiratory Syndrome (SARS) exposed serious limitations in Canada’s ability to respond to a public health emergency. Considerable progress has been made since SARS in addressing these limitations, including the creation of the new Public Health Agency of Canada. A remaining contentious question is whether there is a need for new federal emergency public health powers. Approaches to public health problems are best handled through collaborative processes, recognizing the critical importance of the local public health response. Nevertheless, this paper argues that a legislative back-up plan must be available to the federal government in the event that collaborative relationships break down. At the minimum, legislation should give the federal government the authority to have guaranteed access to surveillance data during a public health emergency. The legislation should also consider providing the federal government with the authority to devote the nation’s resources to the management of an emergency at its earliest stages. However, any legislative approach must be combined with the development of appropriate capacity at the national level to ensure that new powers can be adequately utilized and that required funding reaches public health officials at other levels of government.",,"Wilson, Kumanan",,,,
,PMC,The Novel Human Coronaviruses NL63 and HKU1,http://dx.doi.org/10.1128/JVI.01466-06,PMC1866027,,,,,"['Pyrc, Krzysztof', 'Berkhout, Ben', 'van der Hoek, Lia']",,,,
,PMC,Replicase Genes of Murine Coronavirus Strains A59 and JHM Are Interchangeable: Differences in Pathogenesis Map to the 3′ One-Third of the Genome,http://dx.doi.org/10.1128/JVI.01944-06,PMC1797483,,,"The important roles of the spike protein and other structural proteins in murine coronavirus (MHV) pathogenesis have been demonstrated; however, the role of the replicase gene remains unexplored. We assessed the influence of the replicase genes of the highly neurovirulent MHV-JHM strain and the hepatotropic and mildly neurovirulent A59 strain in acute infection of the mouse. Analysis of chimeric A59/JHM recombinant viruses indicates that the replicase genes are interchangeable and that it is the 3′ end of the genome, encoding the structural proteins, rather than the replicase gene, that determines the pathogenic properties of these chimeras.",,"['Navas-Martin, Sonia', 'Brom, Maarten', 'Chua, Ming-Ming', 'Watson, Richard', 'Qiu, Zhaozhu', 'Weiss, Susan R.']",,,,
,PMC,Lethal Infection of K18-hACE2 Mice Infected with Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.02012-06,PMC1797474,,,"The severe acute respiratory syndrome (SARS), caused by a novel coronavirus (SARS-CoV), resulted in substantial morbidity, mortality, and economic losses during the 2003 epidemic. While SARS-CoV infection has not recurred to a significant extent since 2003, it still remains a potential threat. Understanding of SARS and development of therapeutic approaches have been hampered by the absence of an animal model that mimics the human disease and is reproducible. Here we show that transgenic mice that express the SARS-CoV receptor (human angiotensin-converting enzyme 2 [hACE2]) in airway and other epithelia develop a rapidly lethal infection after intranasal inoculation with a human strain of the virus. Infection begins in airway epithelia, with subsequent alveolar involvement and extrapulmonary virus spread to the brain. Infection results in macrophage and lymphocyte infiltration in the lungs and upregulation of proinflammatory cytokines and chemokines in both the lung and the brain. This model of lethal infection with SARS-CoV should be useful for studies of pathogenesis and for the development of antiviral therapies.",,"['McCray, Paul B.', 'Pewe, Lecia', 'Wohlford-Lenane, Christine', 'Hickey, Melissa', 'Manzel, Lori', 'Shi, Lei', 'Netland, Jason', 'Jia, Hong Peng', 'Halabi, Carmen', 'Sigmund, Curt D.', 'Meyerholz, David K.', 'Kirby, Patricia', 'Look, Dwight C.', 'Perlman, Stanley']",,,,
,PMC,The ORF7b Protein of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Is Expressed in Virus-Infected Cells and Incorporated into SARS-CoV Particles,http://dx.doi.org/10.1128/JVI.01691-06,PMC1797472,,,"Coronavirus replication is facilitated by a number of highly conserved viral proteins. The viruses also encode accessory genes, which are virus group specific and believed to play roles in virus replication and pathogenesis in vivo. Of the eight putative accessory proteins encoded by the severe acute respiratory distress syndrome associated coronavirus (SARS-CoV), only two—open reading frame 3a (ORF3a) and ORF7a—have been identified in virus-infected cells to date. The ORF7b protein is a putative viral accessory protein encoded on subgenomic (sg) RNA 7. The ORF7b initiation codon overlaps the ORF7a stop codon in a −1 shifted ORF. We demonstrate that the ORF7b protein is expressed in virus-infected cell lysates and from a cDNA encoding the gene 7 coding region, indicating that the sgRNA7 is bicistronic. The translation of ORF7b appears to be mediated by ribosome leaky scanning, and the protein has biochemical properties consistent with that of an integral membrane protein. ORF7b localizes to the Golgi compartment and is incorporated into SARS-CoV particles. We therefore conclude that the ORF7b protein is not only an accessory protein but a structural component of the SARS-CoV virion.",,"['Schaecher, Scott R.', 'Mackenzie, Jason M.', 'Pekosz, Andrew']",,,,
,PMC,Suppression of Coronavirus Replication by Inhibition of the MEK Signaling Pathway,http://dx.doi.org/10.1128/JVI.01705-06,PMC1797436,,,"We previously demonstrated that infection of cultured cells with murine coronavirus mouse hepatitis virus (MHV) resulted in activation of the mitogen-activated protein kinase (Raf/MEK/ERK) signal transduction pathway (Y. Cai et al., Virology 355:152-163, 2006). Here we show that inhibition of the Raf/MEK/ERK signaling pathway by the MEK inhibitor UO126 significantly impaired MHV progeny production (a reduction of 95 to 99% in virus titer), which correlated with the phosphorylation status of ERK1/2. Moreover, knockdown of MEK1/2 and ERK1/2 by small interfering RNAs suppressed MHV replication. The inhibitory effect of UO126 on MHV production appeared to be a general phenomenon since the effect was consistently observed in all six different MHV strains and in three different cell types tested; it was likely exerted at the postentry steps of the virus life cycle because the virus titers were similarly inhibited from infected cells treated at 1 h prior to, during, or after infection. Furthermore, the treatment did not affect the virus entry, as revealed by the virus internalization assay. Metabolic labeling and reporter gene assays demonstrated that translation of cellular and viral mRNAs appeared unaffected by UO126 treatment. However, synthesis of viral genomic and subgenomic RNAs was severely suppressed by UO126 treatment, as demonstrated by a reduced incorporation of [(3)H]uridine and a decrease in chloramphenicol acetyltransferase (CAT) activity in a defective-interfering RNA-CAT reporter assay. These findings indicate that the Raf/MEK/ERK signaling pathway is involved in MHV RNA synthesis.",,"['Cai, Yingyun', 'Liu, Yin', 'Zhang, Xuming']",,,,
,PMC,Mouse Hepatitis Virus Does Not Induce Beta Interferon Synthesis and Does Not Inhibit Its Induction by Double-Stranded RNA,http://dx.doi.org/10.1128/JVI.01512-06,PMC1797428,,,"Mouse hepatitis virus (MHV) does not induce interferon (IFN) production in fibroblasts or bone marrow-derived dendritic cells. In this report, we show that the essential IFN-β transcription factors NF-κB and IFN regulatory factor 3 are not activated for nuclear translocation and gene induction during infection. However, MHV was unable to inhibit the activation of these factors and subsequent IFN-β production induced by poly(I:C). Further, MHV infection did not inhibit IFN-β production mediated by known host pattern recognition receptors (PRRs) (RIG-I, Mda-5, and TLR3). These results are consistent with the notion that double-stranded RNA, produced during MHV infection, is not accessible to cellular PRRs.",,"['Zhou, Haixia', 'Perlman, Stanley']",,,,
,PMC,Identifying Epitopes Responsible for Neutralizing Antibody and DC-SIGN Binding on the Spike Glycoprotein of the Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.01138-06,PMC1641789,,,"The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) uses dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) to facilitate cell entry via cellular receptor-angiotensin-converting enzyme 2. For this project, we used recombinant baculoviruses expressing different lengths of SARS-CoV spike (S) protein in a capture assay to deduce the minimal DC-SIGN binding region. Our results identified the region location between amino acid (aa) residues 324 to 386 of the S protein. We then generated nine monoclonal antibodies (MAbs) against the S protein to map the DC-SIGN-binding domain using capture assays with pseudotyped viruses and observed that MAb SIa5 significantly blocked S protein-DC-SIGN interaction. An enhancement assay using the HKU39849 SARS-CoV strain and human immature dendritic cells confirmed our observation. Data from a pepscan analysis and M13 phage peptide display library system mapped the reactive MAb SIa5 epitope to aa residues 363 to 368 of the S protein. Results from a capture assay testing three pseudotyped viruses with mutated N-linked glycosylation sites of the S protein indicate that only two pseudotyped viruses (N330Q and N357Q, both of which lost glycosylation sites near the SIa5 epitope) had diminished DC-SIGN-binding capacity. We also noted that MAb SIb4 exerted a neutralizing effect against HKU39849; its reactive epitope was mapped to aa residues 435 to 439 of the S protein. We offer the data to facilitate the development of therapeutic agents and preventive vaccines against SARS-CoV infection.",,"['Shih, Yi-Ping', 'Chen, Chia-Yen', 'Liu, Shih-Jen', 'Chen, Kuan-Hsuan', 'Lee, Yuan-Ming', 'Chao, Yu-Chan', 'Chen, Yi-Ming Arthur']",,,,
,PMC,Murine Hepatitis Virus Strain 1 Produces a Clinically Relevant Model of Severe Acute Respiratory Syndrome in A/J Mice,http://dx.doi.org/10.1128/JVI.00747-06,PMC1641767,,,"Severe acute respiratory syndrome (SARS) is a life-threatening infectious disease which has been difficult to study and treat because of the lack of a readily available animal model. Intranasal infection of A/J mice with the coronavirus murine hepatitis virus strain 1 (MHV-1) produced pulmonary pathological features of SARS. All MHV-1-infected A/J mice developed progressive interstitial pneumonitis, including dense macrophage infiltrates, giant cells, and hyaline membranes, resulting in death of all animals. In contrast, other mouse strains developed only mild transitory disease. Infected A/J mice had significantly higher cytokine levels, particularly macrophage chemoattractant protein 1 (MCP-1/CCL-2), gamma interferon, and tumor necrosis factor alpha. Furthermore, FGL2/fibroleukin mRNA transcripts and protein and fibrin deposits were markedly increased in the lungs of infected A/J mice. These animals developed a less robust type I interferon response to MHV-1 infection than resistant C57BL/6J mice, and treatment with recombinant beta interferon improved survival. This study describes a potentially useful small animal model of human SARS, defines its pathogenesis, and suggests treatment strategies.",,"['De Albuquerque, Nadine', 'Baig, Ehtesham', 'Ma, Xuezhong', 'Zhang, Jianhua', 'He, William', 'Rowe, Andrea', 'Habal, Marlena', 'Liu, Mingfeng', 'Shalev, Itay', 'Downey, Gregory P.', 'Gorczynski, Reginald', 'Butany, Jagdish', 'Leibowitz, Julian', 'Weiss, Susan R.', 'McGilvray, Ian D.', 'Phillips, M. James', 'Fish, Eleanor N.', 'Levy, Gary A.']",,,,
,PMC,Nonsegmented Negative-Strand Viruses as Vaccine Vectors,http://dx.doi.org/10.1128/JVI.00919-06,PMC1641758,,,,,"['Bukreyev, Alexander', 'Skiadopoulos, Mario H.', 'Murphy, Brian R.', 'Collins, Peter L.']",,,,
,PMC,CC Chemokine Receptor 2 is Protective Against Noise-Induced Hair Cell Death: Studies in CX3CR1(+/GFP) Mice,http://dx.doi.org/10.1007/s10162-006-0051-x,PMC2504633,,,"Acoustic trauma was recently shown to induce an inflammatory response in the ear characterized by rapid entry of macrophages in the spiral ligament. The current study seeks to elucidate the mechanisms involved in summoning macrophages to the cochlear lateral wall and the role macrophages play in noise-induced injury or repair. CCL2 and its primary receptor, CCR2, are the most widely validated effectors of monocyte chemotaxis in vivo. CCL2(−/−) and CCR2(−/−) mice have been used extensively in studies of monocyte activation in neuronal injury. However, the function of CCL2 and CCR2 in the cochlea has not been studied. The present study examines the role of CCL2 and CCR2 in acoustic injury. CCL2(−/−) and CCR2(−/−) mice on a CX3CR1(+/GFP) background were exposed to octave band noise (8–16 kHz) for 2 h to determine the effect of CCL2 and CCR2 on monocyte migration into the cochlea, threshold shift, and cell survival. We found that threshold shift was unchanged in the two knockout mouse strains when compared to the background strain (CX3CR1(+/GFP)). Surprisingly, we found that monocyte migration was also unchanged, despite the absence of CCL2 or CCR2. However, there was a dramatic increase in noise-induced hair cell death in the CCR2(−/−) strain. This observation suggests that CCR2, independent of CCL2, plays a protective role in the cochlea after noise, and neither ligand nor receptor is necessary for monocyte migration. Possible mechanisms of neuroprotection by CCR2 are discussed.",,"['Sautter, Nathan B.', 'Shick, Elizabeth H.', 'Ransohoff, Richard M.', 'Charo,  Israel F.', 'Hirose, Keiko']",,,,
,PMC,Emergence and predominance of an H5N1 influenza variant in China,http://dx.doi.org/10.1073/pnas.0608157103,PMC1636557,,,"The development of highly pathogenic avian H5N1 influenza viruses in poultry in Eurasia accompanied with the increase in human infection in 2006 suggests that the virus has not been effectively contained and that the pandemic threat persists. Updated virological and epidemiological findings from our market surveillance in southern China demonstrate that H5N1 influenza viruses continued to be panzootic in different types of poultry. Genetic and antigenic analyses revealed the emergence and predominance of a previously uncharacterized H5N1 virus sublineage (Fujian-like) in poultry since late 2005. Viruses from this sublineage gradually replaced those multiple regional distinct sublineages and caused recent human infection in China. These viruses have already transmitted to Hong Kong, Laos, Malaysia, and Thailand, resulting in a new transmission and outbreak wave in Southeast Asia. Serological studies suggest that H5N1 seroconversion in market poultry is low and that vaccination may have facilitated the selection of the Fujian-like sublineage. The predominance of this virus over a large geographical region within a short period directly challenges current disease control measures.",,"['Smith, G. J. D.', 'Fan, X. H.', 'Wang, J.', 'Li, K. S.', 'Qin, K.', 'Zhang, J. X.', 'Vijaykrishna, D.', 'Cheung, C. L.', 'Huang, K.', 'Rayner, J. M.', 'Peiris, J. S. M.', 'Chen, H.', 'Webster, R. G.', 'Guan, Y.']",,,,
,PMC,Diagnosis of Human Metapneumovirus Infection in Immunosuppressed Lung Transplant Recipients and Children Evaluated for Pertussis,http://dx.doi.org/10.1128/JCM.01621-06,PMC1829004,,,"Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that is known to cause respiratory tract infections in children and immunocompromised individuals. Given the difficulties of identifying hMPV by conventional culture, molecular techniques could improve the detection of this virus in clinical specimens. In this study, we developed a real-time reverse transcription-PCR (RT-PCR) assay designed to detect the four genetic lineages of hMPV. This assay and a commercial real-time nucleic acid sequence-based amplification (NASBA) assay (bioMérieux, Durham, NC) were used to determine the prevalence of hMPV in 114 immunosuppressed asymptomatic and symptomatic lung transplant recipients and 232 pediatric patients who were being evaluated for pertussis. hMPV was detected in 4.3% of the immunosuppressed lung transplant recipients and in 9.9% of children evaluated for pertussis. Both RT-PCR and NASBA assays were efficient in detection of hMPV infection in respiratory specimens. Even though hMPV was detected in a small number of the lung transplant recipients, it was still the most prevalent etiologic agent detected in patients with respiratory symptoms. In both of these diverse patient populations, hMPV infection was the most frequent viral respiratory tract infection identified. Given our findings, infection with hMPV infection should be determined as part of the differential diagnosis of respiratory illnesses.",,"['Dare, Ryan', 'Sanghavi, Sonali', 'Bullotta, Arlene', 'Keightley, Maria-Cristina', 'George, Kirsten St.', 'Wadowsky, Robert M.', 'Paterson, David L.', 'McCurry, Kenneth R.', 'Reinhart, Todd A.', 'Husain, Shahid', 'Rinaldo, Charles R.']",,,,
,PMC,TB-infected deer are more closely related than non-infected deer,http://dx.doi.org/10.1098/rsbl.2006.0547,PMC2373800,,,Identifying mechanisms of pathogen transmission is critical to controlling disease. Social organization should influence contacts among individuals and thus the distribution and spread of disease within a population. Molecular genetic markers can be used to elucidate mechanisms of disease transmission in wildlife populations without undertaking detailed observational studies to determine probable contact rates. Estimates of genealogical relationships within a bovine tuberculosis-infected white-tailed deer (Odocoileus virginianus) population indicated that infected deer were significantly more closely related than non-infected deer suggesting that contact within family groups was a significant mechanism of disease transmission. Results demonstrate that epidemiological models should incorporate aspects of host ecology likely to affect the probability of disease transmission.,,"['Blanchong, Julie A', 'Scribner, Kim T', 'Kravchenko, Alexandra N', 'Winterstein, Scott R']",,,,
,PMC,IL-13 is associated with reduced illness and replication in primary respiratory syncytial virus infection in the mouse,http://dx.doi.org/10.1016/j.micinf.2006.09.007,PMC1811125,,,"The role of IL-13 in respiratory syncytial virus (RSV) immunopathogenesis is incompletely described. To assess the effect of IL-13 on primary RSV infection, transgenic mice which either overexpress IL-13 in the lung (IL-13 OE) or nontransgenic littermates (IL-13 NT) were challenged intranasally with RSV. IL-13 OE mice had significantly decreased peak viral titers four days after infection compared to non-transgenic littermates. In addition, the IL-13 OE mice had significantly lower RSV-induced weight loss and reduced lung IFN-γ protein expression compared with IL-13 NT mice. In contrast, primary RSV challenge of IL-13 deficient mice resulted in a small, but statistically significant increase in viral titers on day four after infection, no difference in RSV-induced weight loss compared to wild type mice, and augmented IFN-γ production on day 6 after infection. In STAT1-deficient (STAT1 KO) mice, where primary RSV challenge produced high levels of IL-13 production in the lungs, treatment with an IL-13 neutralizing protein resulted in greater peak viral titers both four and six days after RSV and greater RSV-induced weight loss compared to mice treated with a control protein. These results suggest that IL-13 modulates illness from RSV-infection.",,"['Zhou, Weisong', 'Hashimoto, Koichi', 'Moore, Martin L.', 'Elias, Jack A.', 'Zhu, Zhou', 'Durbin, Joan', 'Colasurdo, Giuseppe', 'Rutigliano, John A.', 'Chiappetta, Constance L.', 'Goleniewska, Kasia', 'O’Neal, Jamye F.', 'Graham, Barney S.', 'Peebles, R. Stokes']",,,,
,PMC,Regional collaboration in the Middle East to deal with H5N1 avian flu,http://dx.doi.org/10.1136/bmj.38994.420926.80,PMC1618452,,,In 2005-6 Arab and Israeli collaboration contained outbreaks of avian flu in the Middle East. This initiative shows how building relationships through joint efforts creates an infrastructure for cross border collaboration during emergencies,,"['Leventhal, Alex', 'Ramlawi, Assad', 'Belbiesi, Adel', 'Balicer, Ran D']",,,,
,PMC,Viral Infection of the Lungs through the Eye,http://dx.doi.org/10.1128/JVI.01437-06,PMC1797451,,,"Respiratory syncytial virus (RSV) is the foremost respiratory pathogen in newborns and claims millions of lives annually. However, there has been no methodical study of the pathway(s) of entry of RSV or its interaction with nonrespiratory tissues. We and others have recently established a significant association between allergic conjunctivitis and the presence of RSV in the eye. Here we adopt a BALB/c mouse model and demonstrate that when instilled in the live murine eye, RSV not only replicated robustly in the eye but also migrated to the lung and produced a respiratory disease that is indistinguishable from the standard, nasally acquired RSV disease. Ocularly applied synthetic anti-RSV small interfering RNA prevented infection of the eye as well as the lung. RSV infection of the eye activated a plethora of ocular cytokines and chemokines with profound relevance to inflammation of the eye. Anticytokine treatments in the eye reduced ocular inflammation but had no effect on viral growth in both eye and lung, demonstrating a role of the cytokine response in ocular pathology. These results establish the eye as a major gateway of respiratory infection and a respiratory virus as a bona fide eye pathogen, thus offering novel intervention and treatment options.",,"['Bitko, Vira', 'Musiyenko, Alla', 'Barik, Sailen']",,,,
,PMC,"Pradimicin A, a Carbohydrate-Binding Nonpeptidic Lead Compound for Treatment of Infections with Viruses with Highly Glycosylated Envelopes, Such as Human Immunodeficiency Virus",http://dx.doi.org/10.1128/JVI.01404-06,PMC1797273,,,"Pradimicin A (PRM-A), an antifungal nonpeptidic benzonaphtacenequinone antibiotic, is a low-molecular-weight (molecular weight, 838) carbohydrate binding agent (CBA) endowed with a selective inhibitory activity against human immunodeficiency virus (HIV). It invariably inhibits representative virus strains of a variety of HIV-1 clades with X4 and R5 tropisms at nontoxic concentrations. Time-of-addition studies revealed that PRM-A acts as a true virus entry inhibitor. PRM-A specifically interacts with HIV-1 gp120 and efficiently prevents virus transmission in cocultures of HUT-78/HIV-1 and Sup T1 cells. Upon prolonged exposure of HIV-1-infected CEM cell cultures, PRM-A drug pressure selects for mutant HIV-1 strains containing N-glycosylation site deletions in gp120 but not gp41. A relatively long exposure time to PRM-A is required before drug-resistant virus strains emerge. PRM-A has a high genetic barrier, since more than five N-glycosylation site deletions in gp120 are required to afford moderate drug resistance. Such mutated virus strains keep full sensitivity to the other known clinically used anti-HIV drugs. PRM-A represents the first prototype compound of a nonpeptidic CBA lead and, together with peptide-based lectins, belongs to a conceptually novel type of potential therapeutics for which drug pressure results in the selection of glycan deletions in the HIV gp120 envelope.",,"['Balzarini, Jan', 'Van Laethem, Kristel', 'Daelemans, Dirk', 'Hatse, Sigrid', 'Bugatti, Antonella', 'Rusnati, Marco', 'Igarashi, Yasuhiro', 'Oki, Toshikazu', 'Schols, Dominique']",,,,
,PMC,Identification of Linear Heparin-Binding Peptides Derived from Human Respiratory Syncytial Virus Fusion Glycoprotein That Inhibit Infectivity,http://dx.doi.org/10.1128/JVI.01226-06,PMC1797247,,,"It has been shown previously that the fusion glycoprotein of human respiratory syncytial virus (RSV-F) interacts with cellular heparan sulfate. Synthetic overlapping peptides derived from the F-protein sequence of RSV subtype A (strain A2) were tested for their ability to bind heparin using heparin-agarose affinity chromatography (HAAC). This evaluation identified 15 peptides representing eight linear heparin-binding domains (HBDs) located within F(1) and F(2) and spanning the protease cleavage activation site. All peptides bound to Vero and A549 cells, and binding was inhibited by soluble heparins and diminished by either enzymatic treatment to remove cell surface glycosaminoglycans or by treatment with sodium chlorate to decrease cellular sulfation. RSV-F HBD peptides were less likely to bind to glycosaminoglycan-deficient CHO-745 cells than parental CHO-K1 cells that express these molecules. Three RSV-F HBD peptides (F16, F26, and F55) inhibited virus infectivity; two of these peptides (F16 and F55) inhibited binding of virus to Vero cells, while the third (F26) did not. These studies provided evidence that two of the linear HBDs mapped by peptides F16 and F55 may mediate one of the first steps in the attachment of virus to cells while the third, F26, inhibited infectivity at a postattachment step, suggesting that interactions with cell surface glycosaminoglycans may play a role in infectivity of some RSV strains.",,"['Crim, Roberta L.', 'Audet, Susette A.', 'Feldman, Steven A.', 'Mostowski, Howard S.', 'Beeler, Judy A.']",,,,
,PMC,Protective immunity to lethal challenge of the 1918 pandemic influenza virus by vaccination,http://dx.doi.org/10.1073/pnas.0607564103,PMC1613227,,,"The remarkable infectivity and virulence of the 1918 influenza virus resulted in an unprecedented pandemic, raising the question of whether it is possible to develop protective immunity to this virus and whether immune evasion may have contributed to its spread. Here, we report that the highly lethal 1918 virus is susceptible to immune protection by a preventive vaccine, and we define its mechanism of action. Immunization with plasmid expression vectors encoding hemagglutinin (HA) elicited potent CD4 and CD8 cellular responses as well as neutralizing antibodies. Antibody specificity and titer were defined by a microneutralization and a pseudotype assay that could assess antibody specificity without the need for high-level biocontainment. This pseudotype inhibition assay can define evolving serotypes of influenza viruses and facilitate the development of immune sera and neutralizing monoclonal antibodies that may help contain pandemic influenza. Notably, mice vaccinated with 1918 HA plasmid DNAs showed complete protection to lethal challenge. T cell depletion had no effect on immunity, but passive transfer of purified IgG from anti-H1(1918) immunized mice provided protective immunity for naïve mice challenged with infectious 1918 virus. Thus, humoral immunity directed at the viral HA can protect against the 1918 pandemic virus.",,"['Kong, Wing-pui', 'Hood, Chantelle', 'Yang, Zhi-yong', 'Wei, Chih-Jen', 'Xu, Ling', 'García-Sastre, Adolfo', 'Tumpey, Terrence M.', 'Nabel, Gary J.']",,,,
,PMC,Use of mobile phones in hospitals: New guidelines are less restrictive but still overcautious,http://dx.doi.org/10.1136/bmj.38995.599769.80,PMC1601977,,,,,"['Derbyshire, Stuart W G', 'Burgess, Adam']",,,,
,PMC,Comparative estimation of the reproduction number for pandemic influenza from daily case notification data,http://dx.doi.org/10.1098/rsif.2006.0161,PMC2358966,,,"The reproduction number, R, defined as the average number of secondary cases generated by a primary case, is a crucial quantity for identifying the intensity of interventions required to control an epidemic. Current estimates of the reproduction number for seasonal influenza show wide variation and, in particular, uncertainty bounds for R for the pandemic strain from 1918 to 1919 have been obtained only in a few recent studies and are yet to be fully clarified. Here, we estimate R using daily case notifications during the autumn wave of the influenza pandemic (Spanish flu) in the city of San Francisco, California, from 1918 to 1919. In order to elucidate the effects from adopting different estimation approaches, four different methods are used: estimation of R using the early exponential-growth rate (Method 1), a simple susceptible–exposed–infectious–recovered (SEIR) model (Method 2), a more complex SEIR-type model that accounts for asymptomatic and hospitalized cases (Method 3), and a stochastic susceptible–infectious–removed (SIR) with Bayesian estimation (Method 4) that determines the effective reproduction number [Image: see text] [Formula: see text] at a given time t. The first three methods fit the initial exponential-growth phase of the epidemic, which was explicitly determined by the goodness-of-fit test. Moreover, Method 3 was also fitted to the whole epidemic curve. Whereas the values of R obtained using the first three methods based on the initial growth phase were estimated to be 2.98 (95% confidence interval (CI): 2.73, 3.25), 2.38 (2.16, 2.60) and 2.20 (1.55, 2.84), the third method with the entire epidemic curve yielded a value of 3.53 (3.45, 3.62). This larger value could be an overestimate since the goodness-of-fit to the initial exponential phase worsened when we fitted the model to the entire epidemic curve, and because the model is established as an autonomous system without time-varying assumptions. These estimates were shown to be robust to parameter uncertainties, but the theoretical exponential-growth approximation (Method 1) shows wide uncertainty. Method 4 provided a maximum-likelihood effective reproduction number 2.10 (1.21, 2.95) using the first 17 epidemic days, which is consistent with estimates obtained from the other methods and an estimate of 2.36 (2.07, 2.65) for the entire autumn wave. We conclude that the reproduction number for pandemic influenza (Spanish flu) at the city level can be robustly assessed to lie in the range of 2.0–3.0, in broad agreement with previous estimates using distinct data.",,"['Chowell, Gerardo', 'Nishiura, Hiroshi', 'Bettencourt, Luís M.A']",,,,
,PMC,Role for Nonstructural Protein 1 of Severe Acute Respiratory Syndrome Coronavirus in Chemokine Dysregulation,http://dx.doi.org/10.1128/JVI.02336-05,PMC1797241,,,"Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus. Since its associated morbidity and mortality have been postulated to be due to immune dysregulation, we investigated which of the viral proteins is responsible for chemokine overexpression. To delineate the viral and cellular factor interactions, the role of four SARS coronavirus proteins, including nonstructural protein 1 (nsp-1), nsp-5, envelope, and membrane, were examined in terms of cytokine induction. Our results showed that the SARS coronavirus nsp-1 plays an important role in CCL5, CXCL10, and CCL3 expression in human lung epithelial cells via the activation of NF-κB.",,"['Law, Anna H. Y.', 'Lee, Davy C. W.', 'Cheung, Benny K. W.', 'Yim, Howard C. H.', 'Lau, Allan S. Y.']",,,,
,PMC,Controlling droplet-transmitted respiratory infections: Best practices and cost,,PMC1783603,,,"OBJECTIVE: To promote incorporation of new guidelines on control of respiratory infections into family physicians’ practices. SOURCES OF INFORMATION: The World Health Organization website on pandemic influenza, the Canadian Pandemic Influenza Plan, the Ontario guidelines on respiratory infection control, and research on implementing guidelines into family practice were reviewed. We also researched and calculated what the costs of implementing the guidelines would be. MAIN MESSAGE: Effective control of respiratory infections in physicians’ offices can be achieved by displaying signs in the waiting room, having reception staff give masks to patients with cough and fever, instructing these patients to clean their hands with alcohol gel and to sit at least 1 m from others, inquiring about patients’ or their close contacts’ recent travel, using disinfectant wipes to clean possibly contaminated surfaces in waiting rooms and examining areas, and having staff and care providers wear masks and wash hands or use alcohol gel. The approximate annual cost of incorporating the guidelines is about $800 per physician. CONCLUSION: Because the outbreak of an influenza pandemic is likely imminent, implementing standard guidelines for control of respiratory infections in primary care offices seems wise. Following these guidelines would help prevent patients and staff from contracting serious respiratory illnesses.",,"['Hogg, William', 'Huston, Patricia']",,,,
,PMC,Enhancing public health response to respiratory epidemics: Are family physicians ready and willing to help?,,PMC1783601,,,"OBJECTIVE: To describe Ottawa family physicians’ perceptions of their preparedness to respond to outbreaks of infectious diseases or other public health emergencies and to assess their capacity and willingness to assist in the event of such emergencies. DESIGN: Cross-sectional self-administered survey conducted between February 11 and March 10, 2004. SETTING: The City of Ottawa, Ont, and the Department of Family Medicine at the University of Ottawa. PARTICIPANTS: Ottawa family physicians; respondents can be considered a self-selected sample. MAIN OUTCOME MEASURES: Self-reported office preparedness and physicians’ capacity and willingness to respond to public health emergencies. RESULTS: Response rate was 41%. Of 676 physicians contacted, 274 responded, and of those, 246 completed surveys. About 26% of respondents felt prepared for an outbreak of influenza not well covered by vaccine. About 18% felt prepared for serious respiratory epidemics, such as severe acute respiratory syndrome; about 50% felt unprepared. Most respondents (80%) thought they were not ready to respond to an earthquake. About 77% of physicians were willing to be contacted on an urgent basis in case of a public health emergency. Of these, 94% would assist in immunization clinics, 84% in antibiotic clinics, 58% in assessment centres, 52% in treatment centres, 41% with declaration of death, 26% with home care, and 23% with telephone counseling. CONCLUSION: Family physicians appear to be unprepared for, but willing to address, serious public health emergencies. It is essential to set up effective partnerships between primary care and public health services to support family physicians’ capacity to respond to emergencies. This type of study, along with the creation of a register of available services and of a virtual network for sharing information, is an initial step in assessing primary care response.",,"['Hogg, William', 'Huston, Patricia', 'Martin, Carmel', 'Soto, Enrique']",,,,
,PMC,A seven-helix coiled coil,http://dx.doi.org/10.1073/pnas.0604871103,PMC1622844,,,"Coiled-coil proteins contain a characteristic seven-residue sequence repeat whose positions are designated a to g. The interacting surface between α-helices in a classical coiled coil is formed by interspersing nonpolar side chains at the a and d positions with hydrophilic residues at the flanking e and g positions. To explore how the chemical nature of these core amino acids dictates the overall coiled-coil architecture, we replaced all eight e and g residues in the GCN4 leucine zipper with nonpolar alanine side chains. Surprisingly, the alanine-containing mutant forms a stable α-helical heptamer in aqueous solution. The 1.25-Å resolution crystal structure of the heptamer reveals a parallel seven-stranded coiled coil enclosing a large tubular channel with an unusual heptad register shift between adjacent staggered helices. The overall geometry comprises two interleaved hydrophobic helical screws of interacting cross-sectional a and d layers that have not been seen before. Moreover, asparagines at the a positions play an essential role in heptamer formation by participating in a set of buried interhelix hydrogen bonds. These results demonstrate that heptad repeats containing four hydrophobic positions can direct assembly of complex, higher-order coiled-coil structures with rich diversity for close packing of α-helices.",,"['Liu, Jie', 'Zheng, Qi', 'Deng, Yiqun', 'Cheng, Chao-Sheng', 'Kallenbach, Neville R.', 'Lu, Min']",,,,
,PMC,"Bovine-Like Coronaviruses Isolated from Four Species of Captive Wild Ruminants Are Homologous to Bovine Coronaviruses, Based on Complete Genomic Sequences",http://dx.doi.org/10.1128/JVI.01586-08,PMC2593316,,,"We sequenced and analyzed the full-length genomes of four coronaviruses (CoVs), each from a distinct wild-ruminant species in Ohio: sambar deer (Cervus unicolor), a waterbuck (Kobus ellipsiprymnus), a sable antelope (Hippotragus niger), and a white-tailed deer (Odocoileus virginianus). The fecal samples from the sambar deer, the waterbuck, and the white-tailed deer were collected during winter dysentery outbreaks and sporadic diarrhea cases in 1993 and 1994 (H. Tsunemitsu, Z. R. el-Kanawati, D. R. Smith, H. H. Reed, and L. J. Saif, J. Clin. Microbiol. 33:3264-3269, 1995). A fecal sample from a sable antelope was collected in 2003 from an Ohio wild-animal habitat during the same outbreak when a bovine-like CoV from a giraffe (GiCoV) was isolated (M. Hasoksuz, K. Alekseev, A. Vlasova, X. Zhang, D. Spiro, R. Halpin, S. Wang, E. Ghedin, and L. J. Saif, J. Virol. 81:4981-4990, 2007). For two of the CoVs (sambar deer and waterbuck), complete genomes from both the cell culture-adapted and gnotobiotic-calf-passaged strains were also sequenced and analyzed. Phylogenetically, wild-ruminant CoVs belong to group 2a CoVs, with the closest relatedness to recent bovine CoV (BCoV) strains. High nucleotide identities (99.4 to 99.6%) among the wild-ruminant strains and recent BCoV strains (BCoV-LUN and BCoV-ENT, isolated in 1998) further confirm the close relatedness. Comparative genetic analysis of CoVs of captive wild ruminants with BCoV strains suggests that no specific genomic markers are present that allow discrimination between the bovine strains and bovine-like CoVs from captive wild ruminants; furthermore, no specific genetic markers were identified that defined cell cultured or calf-passaged strains or the host origin of strains. The results of this study confirm prior reports of biologic and antigenic similarities between bovine and wild-ruminant CoVs and suggest that cattle may be reservoirs for CoVs that infect captive wild ruminants or vice versa and that these CoVs may represent host range variants of an ancestral CoV.",,"['Alekseev, Konstantin P.', 'Vlasova, Anastasia N.', 'Jung, Kwonil', 'Hasoksuz, Mustafa', 'Zhang, Xinsheng', 'Halpin, Rebecca', 'Wang, Shiliang', 'Ghedin, Elodie', 'Spiro, David', 'Saif, Linda J.']",,,,
,PMC,Display technologies: application for the discovery of drug and gene delivery agents,http://dx.doi.org/10.1016/j.addr.2006.09.018,PMC1847402,,,"Recognition of molecular diversity of cell surface proteomes in disease is essential for the development of targeted therapies. Progress in targeted therapeutics requires establishing effective approaches for high-throughput identification of agents specific for clinically relevant cell surface markers. Over the past decade, a number of platform strategies have been developed to screen polypeptide libraries for ligands targeting receptors selectively expressed in the context of various cell surface proteomes. Streamlined procedures for identification of ligand-receptor pairs that could serve as targets in disease diagnosis, profiling, imaging and therapy have relied on the display technologies, in which polypeptides with desired binding profiles can be serially selected, in a process called biopanning, based on their physical linkage with the encoding nucleic acid. These technologies include virus/phage display, cell display, ribosomal display, mRNA display and covalent DNA display (CDT), with phage display being by far the most utilized. The scope of this review is the recent advancements in the display technologies with a particular emphasis on molecular mapping of cell surface proteomes with peptide phage display. Prospective applications of targeted compounds derived from display libraries in the discovery of targeted drugs and gene therapy vectors are discussed.",,"['Sergeeva, Anna', 'Kolonin, Mikhail G.', 'Molldrem, Jeffrey J.', 'Pasqualini, Renata', 'Arap, Wadih']",,,,
,PMC,"A second, non-canonical RNA-dependent RNA polymerase in SARS Coronavirus",http://dx.doi.org/10.1038/sj.emboj.7601368,PMC1618104,,,"In (+) RNA coronaviruses, replication and transcription of the giant ∼30 kb genome to produce genome- and subgenome-size RNAs of both polarities are mediated by a cognate membrane-bound enzymatic complex. Its RNA-dependent RNA polymerase (RdRp) activity appears to be supplied by non-structural protein 12 (nsp12) that includes an RdRp domain conserved in all RNA viruses. Using SARS coronavirus, we now show that coronaviruses uniquely encode a second RdRp residing in nsp8. This protein strongly prefers the internal 5′-(G/U)CC-3′ trinucleotides on RNA templates to initiate the synthesis of complementary oligonucleotides of <6 residues in a reaction whose fidelity is relatively low. Distant structural homology between the C-terminal domain of nsp8 and the catalytic palm subdomain of RdRps of RNA viruses suggests a common origin of the two coronavirus RdRps, which however may have evolved different sets of catalytic residues. A parallel between the nsp8 RdRp and cellular DNA-dependent RNA primases is drawn to propose that the nsp8 RdRp produces primers utilized by the primer-dependent nsp12 RdRp.",,"['Imbert, Isabelle', 'Guillemot, Jean-Claude', 'Bourhis, Jean-Marie', 'Bussetta, Cécile', 'Coutard, Bruno', 'Egloff, Marie-Pierre', 'Ferron, François', 'Gorbalenya, Alexander E', 'Canard, Bruno']",,,,
,PMC,"Complete genomic sequences, a key residue in the spike protein and deletions in non-structural protein 3b of US strains of the virulent and attenuated coronaviruses, transmissible gastroenteritis virus and porcine respiratory coronavirus",http://dx.doi.org/10.1016/j.virol.2006.08.051,PMC1850758,,,"Transmissible gastroenteritis virus (TGEV) isolates that have been adapted to passage in cell culture maintain their infectivity in vitro but may lose their pathogenicity in vivo. To better understand the genomic mechanisms for viral attenuation, we sequenced the complete genomes of two virulent TGEV strains and their attenuated counterparts: virulent TGEV Miller M6 and attenuated TGEV Miller M60 and virulent TGEV Purdue and attenuated TGEV Purdue P115, together with the ISU-1 strain of porcine respiratory coronavirus (PRCV-ISU-1), a naturally occurring TGEV deletion mutant with an altered respiratory tropism and reduced virulence. Pairwise comparison at both the nucleotide (nt) and amino acid (aa) levels between virulent and attenuated TGEV strains identified a common change in nt 1753 of the spike gene, resulting in a serine to alanine mutation at aa position 585 of the spike proteins of the attenuated TGEV strains. Alanine was also present in this protein in PRCV-ISU-1. Particularly noteworthy, the serine to alanine mutation resides in the region of the major antigenic site A/B (aa 506-706) that elicites neutralizing antibodies and within the domain mediating the cell surface receptor aminopeptidase N binding (aa 522-744). Comparison of the predicted polypeptide products of ORF3b showed significant deletions in the naturally attenuated PRCV ISU-1 and TGEV Miller M60; these deletions occurred at a common break point, suggesting a related mechanism of recombination that may affect viral virulence or tropism. Sequence comparisons at both genomic and protein levels indicated that PRCV-ISU-1 had a closer relationship with TGEV Miller strains than Purdue strains. Phylogenetic analyses showed that virulence is an evolutionarily labile trait in TGEV and that TGEV strains as a group share a common ancestor with PRCV.",,"['Zhang, Xinsheng', 'Hasoksuz, Mustafa', 'Spiro, David', 'Halpin, Rebecca', 'Wang, Shiliang', 'Stollar, Sarah', 'Janies, Daniel', 'Hadya, Nagesh', 'Tang, Yuxin', 'Ghedin, Elodie', 'Saif, Linda']",,,,
,PMC,Openness is key in fight against disease outbreaks.,,PMC2627501,,,,,"Burns, William",,,,
,PMC,Treating malaria at home in Uganda.,,PMC2627498,,,,,"Nakazibwe, Carolyne",,,,
,PMC,Street food boom in Ghana spurs calls for better hygiene.,,PMC2627494,,,,,"Afele, Mawusi",,,,
,PMC,The globalization of emergency medicine and its importance for public health.,,PMC2627492,,,"Emergency medicine (EM) is a global discipline that provides secondary disease prevention and is also a tool for primary prevention. It is a horizontally integrated system of emergency care consisting of access to EM care; provision of EM care in the community and during transportation of patients; and provision of care at the receiving facility or hospital emergency department. EM can offer many tools to improve public health. These tools include primary disease prevention; interventions for addressing substance abuse and interpersonal violence; education about safety practices; epidemiological surveillance; enrolment of patients in clinical research trials focusing on acute interventions; education and clinical training of health-care providers; and participation in local and regional responses to natural and man-made disasters. Public health advocates and health policy-makers can benefit from the opportunities of EM and can help overcome its challenges. Advocating the establishment and recognition of the specialty of EM worldwide can result in benefits for health-care education, help in incorporating the full scope of EM care into the system of public health, and expand the capabilities of EM for primary and secondary prevention for the benefit of the health of the public.",,"['Anderson, Philip', 'Petrino, Roberta', 'Halpern, Pinchas', 'Tintinalli, Judith']",,,,
,PMC,The role of immunostimulation in the development of postweaning multisystemic wasting syndrome in pigs under field conditions,,PMC1562531,,,"We evaluated the effects of immunostimulation in the development of postweaning multisystemic wasting syndrome (PMWS) in 930 pigs 53 to 54 d old in a grower/finisher barn with a history of PMWS. The pigs were allocated to 5 treatment groups: 4 groups received a single intramuscular injection of RespiSure-ONE (a commercial Mycoplasma hyopneumoniae vaccine; n = 197), Emulsigen (an oil-based adjuvant; n = 172), Alhydrogel (an aluminum-hydroxide-based adjuvant; n = 172), or physiologic saline (n = 218); 1 group received no treatment (n = 171). Pigs affected by PMWS were found in all the groups. Antigen to Porcine circovirus type 2 (PCV-2) was detected by immunohistochemical testing within lesions of mesenteric lymph node, spleen, Peyer’s patch, and lung of affected pigs. There was no significant difference in the incidence of PMWS among the groups. The findings indicate that immunostimulation did not influence the expression of PMWS in this study. Thus, routine vaccination against swine diseases may not significantly contribute to the occurrence of PMWS under field conditions.",,"['Haruna, Julius', 'Hanna, Paul', 'Hurnik, Daniel', 'Ikede, Basil', 'Miller, Lisa', 'Yason, Carmencita']",,,,
,PMC,Emerging Respiratory Viruses: Challenges and Vaccine Strategies,http://dx.doi.org/10.1128/CMR.00005-06,PMC1592697,,,"The current threat of avian influenza to the human population, the potential for the reemergence of severe acute respiratory syndrome (SARS)-associated coronavirus, and the identification of multiple novel respiratory viruses underline the necessity for the development of therapeutic and preventive strategies to combat viral infection. Vaccine development is a key component in the prevention of widespread viral infection and in the reduction of morbidity and mortality associated with many viral infections. In this review we describe the different approaches currently being evaluated in the development of vaccines against SARS-associated coronavirus and avian influenza viruses and also highlight the many obstacles encountered in the development of these vaccines. Lessons learned from current vaccine studies, coupled with our increasing knowledge of the host and viral factors involved in viral pathogenesis, will help to increase the speed with which efficacious vaccines targeting newly emerging viral pathogens can be developed.",,"['Gillim-Ross, Laura', 'Subbarao, Kanta']",,,,
,PMC,Molecular gymnastics at the herpesvirus surface,http://dx.doi.org/10.1038/sj.embor.7400807,PMC1618366,,,"This review analyses recent structural results that provide clues about a possible molecular mechanism for the transmission of a fusogenic signal among the envelope glycoproteins of the herpes simplex virus on receptor binding by glycoprotein gD. This signal triggers the membrane-fusion machinery of the virus—contained in glycoproteins gB, gH and gL—to induce the merging of viral and cellular membranes, and to allow virus entry into target cells. This activating process parallels that of γ-retroviruses, in which receptor binding by the amino-terminal domain of the envelope protein activates the fusogenic potential of the virion in a similar way, despite the different organization of the envelope complexes of these two types of viruses. Therefore, the new structural results on the interaction of gD with its receptors might also provide insights into the mechanism of fusogenic signal transmission in γ-retroviruses. Furthermore, the fusion activation parallels with retroviruses, together with the recently reported structural homology of gB with the rhabdovirus envelope glycoprotein indicate that the complex entry apparatus of herpesviruses appears to be functionally related to that of simpler enveloped viruses.",,"Rey, Félix A",,,,
,PMC,Preparation of His-Tagged Armored RNA Phage Particles as a Control for Real-Time Reverse Transcription-PCR Detection of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JCM.00713-06,PMC1594775,,,"Armored RNA has been increasingly used as both an external and internal positive control in nucleic acid-based assays for RNA virus. In order to facilitate armored RNA purification, a His(6) tag was introduced into the loop region of the MS2 coat protein, which allows the exposure of multiple His tags on the surface during armored RNA assembly. The His-tagged armored RNA particles were purified to homogeneity and verified to be free of DNA contamination in a single run of affinity chromatography. A fragment of severe acute respiratory syndrome coronavirus (SARS-CoV) genome targeted for SARS-CoV detection was chosen for an external positive control preparation. A plant-specific gene sequence was chosen for a universal noncompetitive internal positive control preparation. Both controls were purified by Co(2+) affinity chromatography and were included in a real-time reverse transcription-PCR assay for SARS-CoV. The noncompetitive internal positive control can be added to clinical samples before RNA extraction and enables the identification of potential inhibitive effects without interfering with target amplification. The external control could be used for the quantification of viral loads in clinical samples.",,"['Cheng, Yangjian', 'Niu, Jianjun', 'Zhang, Yongyou', 'Huang, Jianwei', 'Li, Qingge']",,,,
,PMC,Hygieia,,PMC2566063,,,,,,,,,
,PMC,Mapping of medical acronyms and initialisms to Medical Subject Headings (MeSH) across selected systems,,PMC1629436,,,"Introduction: Given the common use of acronyms and initialisms in the health sciences, searchers may be entering these abbreviated terms rather than full phrases when searching online systems. The purpose of this study is to evaluate how various MEDLINE Medical Subject Headings (MeSH) interfaces map acronyms and initialisms to the MeSH vocabulary. Methods: The interfaces used in this study were: the PubMed MeSH database, the PubMed Automatic Term Mapping feature, the NLM Gateway Term Finder, and Ovid MEDLINE. Acronyms and initialisms were randomly selected from 2 print sources. The test data set included 415 randomly selected acronyms and initialisms whose related meanings were found to be MeSH terms. Each acronym and initialism was entered into each MEDLINE MeSH interface to determine if it mapped to the corresponding MeSH term. Separately, 46 commonly used acronyms and initialisms were tested. Results: While performance differed widely, the success rates were low across all interfaces for the randomly selected terms. The common acronyms and initialisms tested at higher success rates across the interfaces, but the differences between the interfaces remained. Conclusion: Online interfaces do not always map medical acronyms and initialisms to their corresponding MeSH phrases. This may lead to inaccurate results and missed information if acronyms and initialisms are used in search strategies.",,"Shultz, Mary",,,,
,PMC,trans Regulation of Cap-Independent Translation by a Viral Subgenomic  RNA,http://dx.doi.org/10.1128/JVI.00991-06,PMC1617300,,,"Many positive-strand RNA viruses generate 3′-coterminal subgenomic mRNAs to allow translation of 5′-distal open reading frames. It is unclear how viral genomic and subgenomic mRNAs compete with each other for the cellular translation machinery. Translation of the uncapped Barley yellow dwarf virus genomic RNA (gRNA) and subgenomic RNA1 (sgRNA1) is driven by the powerful cap-independent translation element (BTE) in their 3′ untranslated regions (UTRs). The BTE forms a kissing stem-loop interaction with the 5′ UTR to mediate translation initiation at the 5′ end. Here, using reporter mRNAs that mimic gRNA and sgRNA1, we show that the abundant sgRNA2 inhibits translation of gRNA, but not sgRNA1, in vitro and in vivo. This trans inhibition requires the functional BTE in the 5′ UTR of sgRNA2, but no translation of sgRNA2 itself is detectable. The efficiency of translation of the viral mRNAs in the presence of sgRNA2 is determined by proximity to the mRNA 5′ end of the stem-loop that kisses the 3′ BTE. Thus, the gRNA and sgRNA1 have “tuned” their expression efficiencies via the site in the 5′ UTR to which the 3′ BTE base pairs. We conclude that sgRNA2 is a riboregulator that switches off translation of replication genes from gRNA while permitting translation of structural genes from sgRNA1. These results reveal (i) a new level of control of subgenomic-RNA gene expression, (ii) a new role for a viral subgenomic RNA, and (iii) a new mechanism for RNA-mediated regulation of translation.",,"['Shen, Ruizhong', 'Rakotondrafara, Aurélie M.', 'Miller, W. Allen']",,,,
,PMC,Cryptic Properties of a Cluster of Dominant Flavivirus Cross-Reactive Antigenic Sites,http://dx.doi.org/10.1128/JVI.00080-06,PMC1617264,,,"A number of flaviviruses are important human pathogens, including yellow fever, dengue, West Nile, Japanese encephalitis, and tick-borne encephalitis (TBE) viruses. Infection with or immunization against any of these viruses induces a subset of antibodies that are broadly flavivirus cross-reactive but do not exhibit significant cross-neutralization. Nevertheless, these antibodies can efficiently bind to the major envelope protein (E), which is the main target of neutralizing and protective antibodies because of its receptor-binding and membrane fusion functions. The structural basis for this phenomenon is still unclear. In our studies with TBE virus, we have provided evidence that such cross-reactive antibodies are specific for a cluster of epitopes that are partially occluded in the cage-like assembly of E proteins at the surfaces of infectious virions and involve—but are not restricted to—amino acids of the highly conserved internal fusion peptide loop. Virus disintegration leads to increased accessibility of these epitopes, allowing the cross-reactive antibodies to bind with strongly increased avidity. The cryptic properties of these sites in the context of infectious virions can thus provide an explanation for the observed lack of efficient neutralizing activity of broadly cross-reactive antibodies, despite their specificity for a functionally important structural element in the E protein.",,"['Stiasny, Karin', 'Kiermayr, Stefan', 'Holzmann, Heidemarie', 'Heinz, Franz X.']",,,,
,PMC,Development and Evaluation of Reverse Transcription-Loop-Mediated Isothermal Amplification Assay for Rapid and Real-Time Detection of Japanese Encephalitis Virus,http://dx.doi.org/10.1128/JCM.01487-06,PMC1698363,,,"The standardization and validation of a one-step, single-tube accelerated quantitative reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay is reported for rapid and real-time detection of Japanese encephalitis virus (JEV). The RT-LAMP assay reported in this study is very simple and rapid; the amplification can be obtained in 30 min under isothermal conditions at 63°C by employing a set of six primers targeting the E gene of JEV. The RT-LAMP assay demonstrated exceptionally higher sensitivity compared to that of RT-PCR, with a detection limit of 0.1 PFU. The specificities of the selected primer sets were established by cross-reactivity studies with other closely related members of the JEV serocomplex as well as by evaluation of healthy human volunteers. The comparative evaluation of the RT-LAMP assay for clinical diagnosis with a limited number of patient cerebrospinal fluid samples revealed 85% concordance with conventional RT-PCR, with a sensitivity and a specificity of 100% and 86%, respectively. The concentration of virus in most of the clinical samples was 10(2) to 10(5) PFU/ml, as determined from the standard curve based on the time of positivity in the samples. In addition, the monitoring of gene amplification can also be visualized with the naked eye by using SYBR green I fluorescent dye. Thus, due to easy operation without a requirement of sophisticated equipment and skilled personnel, the RT-LAMP assay reported here is a valuable tool for the rapid and real-time detection of JEV not only by well-equipped laboratories but also by peripheral diagnostic laboratories with limited financial resources in developing countries.",,"['Parida, M. M.', 'Santhosh, S. R.', 'Dash, P. K.', 'Tripathi, N. K.', 'Saxena, P.', 'Ambuj, S.', 'Sahni, A. K.', 'Lakshmana Rao, P. V.', 'Morita, Kouichi']",,,,
,PMC,Rotavirus Infection Enhances Lipopolysaccharide-Induced Intussusception in a Mouse Model,http://dx.doi.org/10.1128/JVI.01185-06,PMC1676276,,,"Unexpected reports of intussusception after vaccination with the live tetravalent rotavirus vaccine RotaShield resulted in voluntary withdrawal of the vaccine. Intussusception, a condition in which the intestine acutely invaginates upon itself, is the most common cause of intestinal obstruction in children. We report here the development of a mouse model to study rotavirus-induced intussusception. In this model, both homologous murine and heterologous simian rotavirus strains significantly enhanced the rate of lipopolysaccharide (LPS)-induced intussusception, and this enhancement was replication dependent, requiring rotavirus doses of greater than one 50% infectious dose. Rotavirus-induced intussusceptions did not have observable lymphoid lead points, despite the induction of intestinal lymphoid hyperplasia after rotavirus infection. Intussusceptions are also postulated to result from altered intestinal motility, but rotavirus infection had no effect on gastrointestinal transit. LPS-induced intussusception is associated with the induction of inflammatory mediators, and intussusception rates can be modified by inflammatory antagonists. We show that rotavirus infection significantly enhanced serum tumor necrosis factor alpha and gamma interferon cytokine levels after LPS treatment compared to uninfected mice. Together, these data suggest that rotavirus infection sensitized mice to the inflammatory effects of subsequent LPS treatment to enhance intussusception rates.",,"['Warfield, Kelly L.', 'Blutt, Sarah E.', 'Crawford, Sue E.', 'Kang, Gagandeep', 'Conner, Margaret E.']",,,,
,PMC,Comparison of the inhibitory effects of interferon alfacon-1 and ribavirin on yellow fever virus infection in a hamster model,http://dx.doi.org/10.1016/j.antiviral.2006.08.008,PMC1828627,,,"Antiviral compounds were evaluated for efficacy against yellow fever virus (YFV) in a hamster model of YFV-induced liver disease. Challenge with a 10(2) 50% cell culture infectious doses of YFV resulted in a 50–80% mortality rate in female hamsters. Virus was detected by QRT-PCR in liver, kidney, spleen, and serum with peak titers on 4–6 days post-viral challenge (dpi). Serum levels of alkaline phosphatase, alanine aminotransferase (ALT), bilirubin, blood urea nitrogen, potassium, and creatinine were significantly elevated, while serum levels of albumin, amylase, glucose, calcium, globulin, phosphorus, sodium, and total protein were significantly reduced. Packed cell volume and white blood cell count were significantly elevated during the course of the infection. Intraperitoneal treatment of hamsters with 0.5–5 μg/kg/d interferon (IFN) alfacon-1, 100 mg/kg/d viramidine, or 50 mg/kg/d ribavirin, initiated 4 h prior to YFV challenge, resulted in significant improvement in survival and serum ALT levels. Treatment with IFN alfacon-1 or ribavirin starting 2 dpi, also significantly improved survival and serum ALT levels in hamsters challenged with YFV. Pre- and post-virus exposure treatment with IFN alfacon-1 was efficacious in improving disease in YFV-infected hamsters.",,"['Julander, Justin G.', 'Morrey, John D.', 'Blatt, Lawrence M.', 'Schafer, Kristiina', 'Sidwell, Robert W.']",,,,
,PMC,Characterization of White Bream Virus Reveals a Novel Genetic Cluster of Nidoviruses,http://dx.doi.org/10.1128/JVI.01758-06,PMC1642614,,,"The order Nidovirales comprises viruses from the families Coronaviridae (genera Coronavirus and Torovirus), Roniviridae (genus Okavirus), and Arteriviridae (genus Arterivirus). In this study, we characterized White bream virus (WBV), a bacilliform plus-strand RNA virus isolated from fish. Analysis of the nucleotide sequence, organization, and expression of the 26.6-kb genome provided conclusive evidence for a phylogenetic relationship between WBV and nidoviruses. The polycistronic genome of WBV contains five open reading frames (ORFs), called ORF1a, -1b, -2, -3, and -4. In WBV-infected cells, three subgenomic RNAs expressing the structural proteins S, M, and N were identified. The subgenomic RNAs were revealed to share a 42-nucleotide, 5′ leader sequence that is identical to the 5′-terminal genome sequence. The data suggest that a conserved nonanucleotide sequence, CA(G/A)CACUAC, located downstream of the leader and upstream of the structural protein genes acts as the core transcription-regulating sequence element in WBV. Like other nidoviruses with large genomes (>26 kb), WBV encodes in its ORF1b an extensive set of enzymes, including putative polymerase, helicase, ribose methyltransferase, exoribonuclease, and endoribonuclease activities. ORF1a encodes several membrane domains, a putative ADP-ribose 1""-phosphatase, and a chymotrypsin-like serine protease whose activity was established in this study. Comparative sequence analysis revealed that WBV represents a separate cluster of nidoviruses that significantly diverged from toroviruses and, even more, from coronaviruses, roniviruses, and arteriviruses. The study adds to the amazing diversity of nidoviruses and appeals for a more extensive characterization of nonmammalian nidoviruses to better understand the evolution of these largest known RNA viruses.",,"['Schütze, Heike', 'Ulferts, Rachel', 'Schelle, Barbara', 'Bayer, Sonja', 'Granzow, Harald', 'Hoffmann, Bernd', 'Mettenleiter, Thomas C.', 'Ziebuhr, John']",,,,
,PMC,Hemagglutinin (HA) Proteins from H1 and H3 Serotypes of Influenza A Viruses Require Different Antigen Designs for the Induction of Optimal Protective Antibody Responses as Studied by Codon-Optimized HA DNA Vaccines,http://dx.doi.org/10.1128/JVI.01065-06,PMC1642598,,,"Effective antibody responses provide crucial immunity against influenza virus infection. The hemagglutinin (HA) protein is the major target of protective antibody responses induced by viral infection and by vaccination with both inactivated and live-attenuated flu vaccines, but knowledge about the optimal designs of protective HA antigens from different flu serotypes is still limited. In this study, we have significantly improved the immunogenicity of HA-expressing DNA vaccines by using codon-optimized HA sequences for either an H1 serotype (A/NewCal/20/99) or an H3 serotype (A/Panama/2007/99) human influenza A virus and then used these constructs as model antigens to identify the optimal HA antigen designs to elicit high-level protective antibody responses. Two forms of HA antigen, a wild-type, full-length HA and a secreted form with transmembrane (TM) domain-truncated HA, were produced. Both forms of HA DNA vaccines, from either H1 or H3 serotypes, were able to elicit high levels of HA-specific immunoglobulin G responses in immunized rabbits as measured by enzyme-linked immunosorbent assay. Interestingly, the abilities of H1 HA and H3 HA antigens to elicit hemagglutination inhibition (HI) and neutralizing antibody (NAb) responses differ. For the H1 HA antigens, the full-length HA induced significantly higher HI and NAb responses than did the TM-truncated HA. For the H3 HA antigen, both the full-length HA and TM-truncated HA induced high levels of HI and NAb responses. These data indicate that H1 and H3 antigens have different expression requirements for the induction of an optimal protective antibody response and that the structure integrity of HA antigens is critical for eliciting type-specific protective antibody responses. Our findings will have an important impact on future subunit-based flu vaccine development.",,"['Wang, Shixia', 'Taaffe, Jessica', 'Parker, Christopher', 'Solórzano, Alicia', 'Cao, Hong', 'García-Sastre, Adolfo', 'Lu, Shan']",,,,
,PMC,Pairwise coupling analysis of helical junction hydrogen bonding interactions in luteoviral RNA pseudoknots,http://dx.doi.org/10.1021/bi060430n,PMC2573051,,,"A 28-nucleotide mRNA pseudoknot that overlaps the P1 and P2 genes of sugarcane yellow leaf virus (ScYLV) stimulates −1 ribosomal frameshifting. The in vitro frameshifting efficiency is decreased ≈8 fold upon substitution of the 3′ most loop 2 nucleotide (C27) to adenosine, which accepts a hydrogen bond from the 2′-OH of C14 in stem S1. The solution structures of the wild-type (WT) and the C27A ScYLV RNA pseudoknots show that while the RNAs adopt virtually identical overall structures, there are significant structural differences at the helical junctions of the two RNAs. Specifically, C8(+) in loop L1 in the C8(+)·(G12-C28) L1-S2 major groove base triple is displaced by ≈2.3 Å relative to the accepting stem 2 base pair (G12-C28) in the C27A RNA. Here, we employ a double mutant cycle approach to analyze the pairwise coupling of the C8(+)·(G12-C28) and C27·(C14-G7) or A27·(C14-G7) hydrogen bonds in the WT and C27A ScYLV RNAs, respectively, and compare these findings with previous results from the beet western yellows virus (BWYV) RNA. We find that the pairwise coupling free energy (δ(AB)(i)) is favorable for the WT RNA (–0.7 ±0.1 kcal·mol(−1)), thus revealing that formation of these two hydrogen bonds is positively cooperative. In contrast, δ(AB)(i) is +0.9 ±0.4 kcal·mol(−1) for the poorly functional C27A ScYLV RNA, indicative of non-additive hydrogen bond formation. These results reveal that cooperative hydrogen bond formation across the helical stem junction in H-type pseudoknots correlates with enhanced frameshift stimulation by luteoviral mRNA pseudoknots.",,"['Cornish, Peter V.', 'Giedroc, David P.']",,,,
,PMC,Rat Strains Differ in Susceptibility to Ureaplasma parvum-Induced Urinary Tract Infection and Struvite Stone Formation,http://dx.doi.org/10.1128/IAI.00984-06,PMC1698052,,,"Individuals with struvite uroliths are susceptible to recurrent urinary tract infections (UTI), sepsis, and renal disease. Unfortunately, little is known about the host-specific factors that predispose to this disease. In order to develop a rodent model that can address this problem, we inoculated female Fischer 344 (F344), Lewis (LEW), Sprague-Dawley (SD), and Wistar (WIS) rats with a host-adapted strain of Ureaplasma parvum. Animals were necropsied at 2 weeks postinoculation; 100% of F344, 42% of SD, 10% of LEW, and 10% of WIS rats remained infected. Severe bladder lesions and struvite calculi were seen in 64% of F344 rats; in other rat strains, bladder lesions were mild or absent. F344 rats with struvite uroliths had the highest urinary levels of proinflammatory cytokines, such as GRO/KC, interleukin-1α (IL-1α), and IL-1β. F344 rats without struvite stones at necropsy had milder bladder lesions and significantly lower urinary levels of proinflammatory cytokines but a more prominent inflammatory response than did other rat strains. Based on our results, struvite stone formation is linked to a robust inflammatory response that does not resolve UTI but instead promotes damage to surrounding tissues.",,"['Reyes, Leticia', 'Reinhard, Mary', ""O'Donell, L. J."", 'Stevens, Janet', 'Brown, Mary B.']",,,,
,PMC,WHO announces 13 candidates for the post of director general,,PMC1569980,,,,,"Glusker, Anne",,,,
,PMC,Human hepatic sinusoidal endothelial cells can be distinguished by expression of phenotypic markers related to their specialised functions in vivo,http://dx.doi.org/10.3748/wjg.v12.i34.5429,PMC4088223,,,"The hepatic sinusoids are lined by a unique population of hepatic sinusoidal endothelial cells (HSEC), which is one of the first hepatic cell populations to come into contact with blood components. However, HSEC are not simply barrier cells that restrict the access of blood-borne compounds to the parenchyma. They are functionally specialised endothelial cells that have complex roles, including not only receptor-mediated clearance of endotoxin, bacteria and other compounds, but also the regulation of inflammation, leukocyte recruitment and host immune responses to pathogens. Thus understanding the differentiation and function of HSEC is critical for the elucidation of liver biology and pathophysiology. This article reviews methods for isolating and studying human hepatic endothelial cell populations using in vitro models. We also discuss the expression and functions of phenotypic markers, such as the presence of fenestrations and expression of VAP-1, Stabilin-1, L-SIGN, which can be used to identify sinusoidal endothelium and to permit discrimination from vascular and lymphatic endothelial cells.",,"['Lalor, PF', 'Lai, WK', 'Curbishley, SM', 'Shetty, S', 'Adams, DH']",,,,
,PMC,Will Research Sharing Keep Pace with the Internet?,http://dx.doi.org/10.1523/JNEUROSCI.3130-06.2006,PMC6674599,,,,,"Johnson, Richard K.",,,,
,PMC,Cross-Protection against a Human Enteric Coronavirus and a Virulent Bovine Enteric Coronavirus in Gnotobiotic Calves,http://dx.doi.org/10.1128/JVI.00402-06,PMC1676286,,,"A group 2 human coronavirus designated HECV-4408 was isolated from a child with acute diarrhea and is antigenically and genetically more closely related to bovine coronavirus (BCoV) than to human coronavirus OC43 (X. M. Zhang, W. Herbst, K. G. Kousoulas, and J. Storz, J. Med. Virol. 44:152-161, 1994). To determine whether HECV-4408 infects gnotobiotic calves and induces cross-protective immunity against the virulent enteric BCoV DB2 strain, gnotobiotic calves (n = 4) were orally inoculated with HECV-4408 and then challenged with BCoV DB2 at postinoculation day (PID) 21. All calves inoculated with HECV-4408 developed diarrhea at PID 3 to 4 lasting 5 to 9 days. Fecal and nasal virus shedding were first detected by reverse transcription-PCR at PID 3 to 4 and at PID 2 to 4, respectively. After challenge with bovine coronavirus, no diarrhea or virus shedding was detected in calves inoculated with HECV-4408, but a mock-inoculated calf developed diarrhea and fecal and nasal shedding. Fecal immunoglobulin A (IgA) and serum IgG antibodies were first detected at PID 7 and PID 14, respectively. At postchallenge day 7, serum IgG and fecal IgA antibody titers remained the same or increased only twofold compared to prechallenge titers. An additional two gnotobiotic calves were inoculated with HECV-4408 and euthanized at PID 5. Moderate villous atrophy was observed in the small intestines, and viral antigen was detected in villous enterocytes of the small and large intestines by immunohistochemistry. These results support and extend the previous report that HECV-4408 is likely a variant of bovine coronavirus. They confirm its infectivity for calves and complete cross-protection against a bovine coronavirus (DB2 strain) showing 98.2% amino acid identity to HECV-4408 in the S protein.",,"['Han, Myung Guk', 'Cheon, Doo-Sung', 'Zhang, Xuming', 'Saif, Linda J.']",,,,
,PMC,"Replication of Murine Hepatitis Virus Is Regulated by Papain-Like Proteinase 1 Processing of Nonstructural Proteins 1, 2, and 3",http://dx.doi.org/10.1128/JVI.01428-06,PMC1642617,,,"Coronaviruses are positive-strand RNA viruses that translate their genome RNA into polyproteins that are co- and posttranslationally processed into intermediate and mature replicase nonstructural proteins (nsps). In murine hepatitis virus (MHV), nsps 1, 2, and 3 are processed by two papain-like proteinase activities within nsp3 (PLP1 and PLP2) to yield nsp1, an nsp2-3 intermediate, and mature nsp2 and nsp3. To determine the role in replication of processing between nsp2 and nsp3 at cleavage site 2 (CS2) and PLP1 proteinase activity, mutations were engineered into the MHV genome at CS2, at CS1 and CS2, and at the PLP1 catalytic site, alone and in combination. Mutant viruses with abolished cleavage at CS2 were delayed in growth and RNA synthesis but grew to wild-type titers of >10(7) PFU/ml. Mutant viruses with deletion of both CS1 and CS2 exhibited both a delay in growth and a decrease in peak viral titer to ∼10(4) PFU/ml. Inactivation of PLP1 catalytic residues resulted in a mutant virus that did not process at either CS1 or CS2 and was severely debilitated in growth, achieving only 10(2) PFU/ml. However, when both CS1 and CS2 were deleted in the presence of inactivated PLP1, the growth of the resulting mutant virus was partially compensated, comparable to that of the CS1 and CS2 deletion mutant. These results demonstrate that interactions of PLP1 with CS1 and CS2 are critical for protein processing and suggest that the interactions play specific roles in regulation of the functions of nsp1, 2, and 3 in viral RNA synthesis.",,"['Graham, Rachel L.', 'Denison, Mark R.']",,,,
,PMC,Molecular Epidemiology of the Foot-and-Mouth Disease Virus Outbreak in the United Kingdom in 2001,http://dx.doi.org/10.1128/JVI.01236-06,PMC1642183,,,"The objective of this study was to quantify the extent to which the genetic diversity of foot-and-mouth disease virus (FMDV) arising over the course of infection of an individual animal becomes fixed, is transmitted to other animals, and thereby accumulates over the course of an outbreak. Complete consensus sequences of 23 genomes (each of 8,200 nucleotides) of FMDV were recovered directly from epithelium tissue acquired from 21 farms infected over a nearly 7-month period during the 2001 FMDV outbreak in the United Kingdom. An analysis of these consensus sequences revealed very few apparently ambiguous sites but clear evidence of 197 nucleotide substitutions at 191 different sites. We estimated the rate of nucleotide substitution to be 2.26 × 10(−5) per site per day (95% confidence interval [CI], 1.75 × 10(−5) to 2.80 × 10(−5)) and nucleotide substitutions to accrue in the consensus sequence at an average rate of 1.5 substitutions per farm infection. This is a sufficiently high rate showing that detailed histories of the transmission pathways can be reliably reconstructed. Coalescent methods indicated that the date at which FMDV first infected livestock in the United Kingdom was 7 February 2001 (95% CI, 20 January to 19 February 2001), which was identical to estimates obtained on the basis of purely clinical evidence. Nucleotide changes appeared to have occurred evenly across the genome, and within the open reading frame, the ratio of nonsynonymous-to-synonymous change was 0.09. The ability to recover particular transmission pathways of acutely acting RNA pathogens from genetic data will help resolve uncertainties about how virus is spread and could help in the control of future epidemics.",,"['Cottam, Eleanor M.', 'Haydon, Daniel T.', 'Paton, David J.', 'Gloster, John', 'Wilesmith, John W.', 'Ferris, Nigel P.', 'Hutchings, Geoff H.', 'King, Donald P.']",,,,
,PMC,Promoting best practices for control of respiratory infections: Collaboration between primary care and public health services,,PMC1783740,,,"OBJECTIVE: To determine the effectiveness of a short-term intervention to promote best practices for control of respiratory infections in primary care physicians’ offices. DESIGN: Before-after observational study. SETTING: Family physicians’ offices in Ottawa, Ont. PARTICIPANTS: General practitioners and office staff. INTERVENTIONS: Four infection-control practices (use of masks, alcohol-based hand gel, and signs, and asking patients to sit at least 1 m apart in the waiting room) were observed, and 2 reported infection-control practices (disinfecting surfaces and use of hand-gel dispensers in examining rooms) were audited before the intervention and 6 weeks after the intervention. MAIN OUTCOME MEASURES: Percentage of patients asked to use masks and alcohol-based hand gel, number of relevant signs, and percentage of patients asked to sit at least 1 m away from other patients. Percentage of surfaces disinfected and percentage of physicians using hand-gel dispensers in examining rooms. RESULTS: Of 242 practices invited, 53 agreed to participate (22% response rate), and within those practices, 143/151 (95%) physicians participated. Signs regarding respiratory infection control measures increased from 15.4% to 81.1% following the intervention (P < .001). At least 1 patient with cough and fever was given a mask in 17% of practices before the intervention; during the observation period after the intervention, at least 1 patient was given a mask in 66.7% of practices (P < .001). Patients were instructed to use alcohol-based hand gel in 24.5% of practices before the intervention and in 79.2% of practices after it (P < .001). Instruction to sit at least 1 m from others in the waiting area was given in 39.6% of practices before the intervention and in 52.8% of practices following the intervention (P < .001). Before the intervention, the percentage of practices using all 4 audited primary prevention measures was 3.8%; after the intervention, 52.8% of practices were using them (P < .001), demonstrating a 49% increase in adoption of best practices. CONCLUSION: A multifaceted intervention by public health nurses successfully promoted best practices for control of respiratory infections in primary care offices. Collaboration between public health services and primary care can promote best practices and warrants further study and development in areas of common interest.",,"['Hogg, William', 'Huston, Patricia', 'Martin, Carmel', 'Saginur, Raphael', 'Newbury, Adriana', 'Vilis, Eileen', 'Soto, Enrique']",,,,
,PMC,The Role of the Proteasome-Ubiquitin Pathway in Regulation of the IFN-γ Mediated Anti-VSV Response in Neurons,http://dx.doi.org/10.1016/j.jneuroim.2006.07.018,PMC1764816,,,"Pharmacologic inhibition of the proteasome resulted in increased NOS-1 protein levels and increased NO production by neuronal cells. This correlated with an increased antiviral effect of IFN-γ against the replication of vesicular stomatitis virus (VSV) replication in vitro. We also observed that a regulatory protein, Protein Inhibitor of NOS-1 (PIN) was down-regulated by IFN-γ treatment, and more ubiquitinated PIN accumulated in IFN-γ treated neurons. In cells of the reticuloendothelial system, IFN-γ treatment induces the expression of a set of low molecular weight MHC-encoded proteins (LMPs), which replace the β -subunit of the proteasome complex during the proteasome neosynthesis, resulting in a complex termed the immunoproteasome. LMP-2,- 7, and -10 were induced and the immunoproteasome was generated by IFN-γ treatment in neuronal cells. Importantly, we observed that IFN-γ induced inhibition of VSV protein synthesis was not dependent on ubiquitination.",,"['Yang, Jingjun', 'Tugal, Derin', 'Reiss, Carol Shoshkes']",,,,
,PMC,Alteration of peripheral blood lymphocyte subsets in acute pancreatitis,http://dx.doi.org/10.3748/wjg.v12.i33.5344,PMC4088202,,,"AIM: To evaluate peripheral blood lymphocyte subsets in patients with acute pancreatitis (AP). METHODS: Twenty patients with mild AP (M-AP) and 15 with severe AP (S-AP) were included in our study. Peripheral blood lymphocytes were examined at d 1-3, 5, 10 and 30 by means of flow cytometry. RESULTS: A significant depletion of circulating lymphocytes was found in AP. In the early AP, the magnitude of depletion was similar for T- and B- lymphocytes. In the late course of S-AP, B-lymphocytes were much more depleted than T-lymphocytes. At d 10, strong shift in the CD7+/CD19+ ratio implicating predominance of T- over B-lymphocytes in S-AP was found. Among T-lymphocytes, the significant depletion of the CD4+ population was observed in M-AP and S-AP, while CD8+ cells were in the normal range. Lymphocytes were found to strongly express activation markers: CD69, CD25, CD28, CD38 and CD122. Serum interleukin-2 (IL-2), IL-4, IL-5, IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) levels were significantly increased in both forms of AP. The magnitude of elevation of cytokines known to be produced by Th2 was much higher than cytokines produced by Th1 cells. CONCLUSION: AP in humans is characterized by significant reduction of peripheral blood T- and B-lymphocytes.",,"['Pietruczuk, Miroslawa', 'Dabrowska, Milena I', 'Wereszczynska-Siemiatkowska, Urszula', 'Dabrowski, Andrzej']",,,,
,PMC,Cooperative Involvement of the S1 and S2 Subunits of the Murine Coronavirus Spike Protein in Receptor Binding and Extended Host Range,http://dx.doi.org/10.1128/JVI.00950-06,PMC1642182,,,"To study the process of spike (S)-receptor interaction during coronavirus entry, we evaluated the contributions of mutations in different regions of the murine hepatitis virus (MHV) S protein to natural receptor murine carcinoembryonic antigen-related cell adhesion molecule 1a (CEACAM1a) dependence and to the acquisition of extended host range. Extended-host-range variants of MHV strain A59 were previously obtained from persistently infected cells (J. H. Schickli, B. D. Zelus, D. E. Wentworth, S. G. Sawicki, and K. V. Holmes, J. Virol. 71:9499-9504, 1997). These variant viruses contain several mutations in the S protein that confer to the viruses the ability to enter cells in a heparan sulfate-dependent manner (C. A. de Haan, Z. Li, E. te Lintelo, B. J. Bosch, B. J. Haijema, and P. J. M. Rottier, J. Virol. 79:14451-14456, 2005). While the parental MHV-A59 is fully dependent on murine CEACAM1a for its entry, viruses carrying the variant mutations in the amino-terminal part of their S protein had become dependent on both CEACAM1a and heparan sulfate. Substitutions in a restricted, downstream part of the S protein encompassing heptad repeat region 1 (HR1) and putative fusion peptide (FP) did not alter the CEACAM1a dependence. However, when the mutations in both parts of the S protein were combined, the resulting viruses became independent of CEACAM1a and acquired the extended host range. In addition, these viruses showed a decreased binding to and inhibition by soluble CEACAM1a. The observations suggest that the amino-terminal region of the S protein, including the receptor-binding domain, and a region in the central part of the S protein containing HR1 and FP, i.e., regions far apart in the linear sequence, communicate and may even interact physically in the higher-order structure of the spike.",,"['de Haan, Cornelis A. M.', 'te Lintelo, Eddie', 'Li, Zhen', 'Raaben, Matthijs', 'Wurdinger, Tom', 'Bosch, Berend Jan', 'Rottier, Peter J. M.']",,,,
,PMC,Persistent Hepatitis C Virus Infection In Vitro: Coevolution of Virus and Host,http://dx.doi.org/10.1128/JVI.01307-06,PMC1642175,,,"The virological and cellular consequences of persistent hepatitis C virus (HCV) infection have been elusive due to the absence of the requisite experimental systems. Here, we report the establishment and the characteristics of persistent in vitro infection of human hepatoma-derived cells by a recently described HCV genotype 2a infectious molecular clone. Persistent in vitro infection was characterized by the selection of viral variants that displayed accelerated expansion kinetics, higher peak titers, and increased buoyant densities. Sequencing analysis revealed the selection of a single adaptive mutation in the HCV E2 envelope protein that was largely responsible for the variant phenotype. In parallel, as the virus became more aggressive, cells that were resistant to infection emerged, displaying escape mechanisms operative at the level of viral entry, HCV RNA replication, or both. Collectively, these results reveal the existence of coevolutionary events during persistent HCV infection that favor survival of both virus and host.",,"['Zhong, Jin', 'Gastaminza, Pablo', 'Chung, Josan', 'Stamataki, Zania', 'Isogawa, Masanori', 'Cheng, Guofeng', 'McKeating, Jane A.', 'Chisari, Francis V.']",,,,
,PMC,Integrated Molecular Signature of Disease: Analysis of Influenza Virus-Infected Macaques through Functional Genomics and Proteomics,http://dx.doi.org/10.1128/JVI.00851-06,PMC1641753,,,"Recent outbreaks of avian influenza in humans have stressed the need for an improved nonhuman primate model of influenza pathogenesis. In order to further develop a macaque model, we expanded our previous in vivo genomics experiments with influenza virus-infected macaques by focusing on the innate immune response at day 2 postinoculation and on gene expression in affected lung tissue with viral genetic material present. Finally, we sought to identify signature genes for early infection in whole blood. For these purposes, we infected six pigtailed macaques (Macaca nemestrina) with reconstructed influenza A/Texas/36/91 virus and three control animals with a sham inoculate. We sacrificed one control and two experimental animals at days 2, 4, and 7 postinfection. Lung tissue was harvested for pathology, gene expression profiling, and proteomics. Blood was collected for genomics every other day from each animal until the experimental endpoint. Gross and microscopic pathology, immunohistochemistry, viral gene expression by arrays, and/or quantitative real-time reverse transcription-PCR confirmed successful yet mild infections in all experimental animals. Genomic experiments were performed using macaque-specific oligonucleotide arrays, and high-throughput proteomics revealed the host response to infection at the mRNA and protein levels. Our data showed dramatic differences in gene expression within regions in influenza virus-induced lesions based on the presence or absence of viral mRNA. We also identified genes tightly coregulated in peripheral white blood cells and in lung tissue at day 2 postinoculation. This latter finding opens the possibility of using gene expression arrays on whole blood to detect infection after exposure but prior to onset of symptoms or shedding.",,"['Baas, T.', 'Baskin, C. R.', 'Diamond, D. L.', 'García-Sastre, A.', 'Bielefeldt-Ohmann, H.', 'Tumpey, T. M.', 'Thomas, M. J.', 'Carter, V. S.', 'Teal, T. H.', 'Van Hoeven, N.', 'Proll, S.', 'Jacobs, J. M.', 'Caldwell, Z. R.', 'Gritsenko, M. A.', 'Hukkanen, R. R.', 'Camp, D. G.', 'Smith, R. D.', 'Katze, M. G.']",,,,
,PMC,Induction of transcription factor Egr-1 gene expression in astrocytoma cells by Murine coronavirus infection,http://dx.doi.org/10.1016/j.virol.2006.07.012,PMC1851928,,,"Mouse hepatitis virus (MHV) causes encephalitis and demyelination in the central nervous system (CNS) of susceptible rodents. Astrocytes are one of the major targets for MHV infection in the CNS, and respond to MHV infection by expressing diverse molecules that may contribute to CNS pathogenesis. Here we characterized the activation of an immediate-early transcription factor Egr-1 by MHV infection in an astrocytoma cell line. We found that the expression of Egr-1 was dramatically increased following virus infection. Using various inhibitors of mitogen-activated protein kinases, we identified that the extracellular signal-regulated kinases 1/2 were involved in the activation of Egr-1 transcription by MHV infection. Experiments with ultraviolet light-inactivated virus revealed that the induction of Egr-1 did not require virus replication and was likely mediated during cell entry. We further found that over-expression of Egr-1 suppressed the expression of BNip3, a pro-apoptotic member of the Bcl-2 family. This finding may provide an explanation for our previously observed down-regulation of BNip3 by MHV infection in astrocytoma cells (Cai, Liu, Yu, and Zhang, Virology 316:104–115, 2003). Furthermore, knockdown of Egr-1 by an siRNA inhibited MHV propagation, suggesting the biological relevance of Egr-1 induction to virus replication. In addition, the persistence/demylinating-positive strains (JHM and A59) induced Egr-1 expression, whereas the persistence/demylinating-negative strain (MHV-2) did not. These results indicate a correlation between the ability of MHVs to induce Egr-1 expression and their ability to cause demyelination in the CNS, which may suggest a potential role for the induction of Egr-1 in viral pathogenesis.",,"['Cai, Yingyun', 'Liu, Yin', 'Zhang, Xuming']",,,,
,PMC,Social Accountability in Theory and Practice,http://dx.doi.org/10.1370/afm.559,PMC1578672,,,,,"Rourke, James",,,,
,PMC,Visible-Light-Induced Bactericidal Activity of a Nitrogen-Doped Titanium Photocatalyst against Human Pathogens,http://dx.doi.org/10.1128/AEM.02580-05,PMC1563686,,,"The antibacterial activity of photocatalytic titanium dioxide (TiO(2)) substrates is induced primarily by UV light irradiation. Recently, nitrogen- and carbon-doped TiO(2) substrates were shown to exhibit photocatalytic activities under visible-light illumination. Their antibacterial activity, however, remains to be quantified. In this study, we demonstrated that nitrogen-doped TiO(2) substrates have superior visible-light-induced bactericidal activity against Escherichia coli compared to pure TiO(2) and carbon-doped TiO(2) substrates. We also found that protein- and light-absorbing contaminants partially reduce the bactericidal activity of nitrogen-doped TiO(2) substrates due to their light-shielding effects. In the pathogen-killing experiment, a significantly higher proportion of all tested pathogens, including Shigella flexneri, Listeria monocytogenes, Vibrio parahaemolyticus, Staphylococcus aureus, Streptococcus pyogenes, and Acinetobacter baumannii, were killed by visible-light-illuminated nitrogen-doped TiO(2) substrates than by pure TiO(2) substrates. These findings suggest that nitrogen-doped TiO(2) has potential application in the development of alternative disinfectants for environmental and medical usages.",,"['Wong, Ming-Show', 'Chu, Wen-Chen', 'Sun, Der-Shan', 'Huang, Hsuan-Shun', 'Chen, Jiann-Hwa', 'Tsai, Pei-Jane', 'Lin, Nien-Tsung', 'Yu, Mei-Shiuan', 'Hsu, Shang-Feng', 'Wang, Shih-Lien', 'Chang, Hsin-Hou']",,,,
,PMC,Tweaking Innate Immunity: the Promise of Innate Immunologicals As Anti-infectives,,PMC2095083,,,"New and exciting insights into the importance of the innate immune system are revolutionizing our understanding of immune defense against infections, pathogenesis, and the treatment and prevention of infectious diseases. The innate immune system uses multiple families of germline-encoded pattern recognition receptors (PRRs) to detect infection and trigger a variety of antimicrobial defense mechanisms. PRRs are evolutionarily highly conserved and serve to detect infection by recognizing pathogen-associated molecular patterns that are unique to microorganisms and essential for their survival. Toll-like receptors (TLRs) are transmembrane signalling receptors that activate gene expression programs that result in the production of proinflammatory cytokines and chemokines, type I interferons and antimicrobial factors. Furthermore, TLR activation facilitates and guides activation of adaptive immune responses through the activation of dendritic cells. TLRs are localized on the cell surface and in endosomal/lysosomal compartments, where they detect bacterial and viral infections. In contrast, nucleotide-binding oligomerization domain proteins and RNA helicases are located in the cell cytoplasm, where they serve as intracellular PRRs to detect cytoplasmic infections, particularly viruses. Due to their ability to enhance innate immune responses, novel strategies to use ligands, synthetic agonists or antagonists of PRRs (also known as ‘innate immunologicals’) can be used as stand-alone agents to provide immediate protection or treatment against bacterial, viral or parasitic infections. Furthermore, the newly appreciated importance of innate immunity in initiating and shaping adaptive immune responses is contributing to our understanding of vaccine adjuvants and promises to lead to improved next-generation vaccines.",,"Rosenthal, Kenneth L",,,,
,PMC,"Needs, Gaps and Opportunities for Infectious Disease Research in British Columbia: A Perspective from Population and Public Health",http://dx.doi.org/10.1007/BF03405394,PMC6975993,,,"BACKGROUND: A review of infectious disease research activity and capacity was performed in British Columbia and linked to a process for identifying needs, gaps and opportunities from a public health perspective. METHODS: The study was organized in three phases: an environmental scan to describe current research activity in BC; a consultation to identify needs, gaps and opportunities with those conducting research (key informants) and the end users of research results (stakeholders); and a prioritization of the research needs emerging from the consultation. RESULTS: Analysis and synthesis of the consultation data resulted in the identification of nine research themes, which were prioritized in the following order: efficacy and cost-benefit, disease patterns, emerging infectious disease, immunology and vaccines, disease-specific research, health promotion and communications, safe food and water, knowledge translation research and genomics. Six capacity-building themes were also identified: attraction and retention, education and training, collaboration and networks, funding, dissemination of findings, and public health input, surveillance, informatics and databases. INTERPRETATION: The findings were helpful in developing a multi-disciplinary, multi-level infectious disease research agenda linking researchers in universities, hospitals and public health institutions with practitioners and policy-makers in British Columbia’s public health system. The approach is both feasible and important to undertake at the national level. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/BF03405394 and is accessible for authorized users.",,"['Patrick, David M.', 'Remple, Valencia P.', 'Kendall, Perry', 'Brunham, Robert C.']",,,,
,PMC,Control of Infectious Animal Diseases by Vaccination,,PMC1555690,,,,,,,,,
,PMC,Isolation of High-Affinity Single-Chain Antibodies against Mycobacterium avium subsp. paratuberculosis Surface Proteins from Sheep with Johne's Disease,http://dx.doi.org/10.1128/CVI.00163-06,PMC1563570,,,"Johne's disease, caused by infection with Mycobacterium avium subsp. paratuberculosis, causes significant economic losses to the livestock farming industry. Improved investigative and diagnostic tools—necessary to understand disease processes and to identify subclinical infection—are much sought after. Here, we describe the production of single-chain antibodies with defined specificity for M. avium subsp. paratuberculosis surface proteins. Single-chain antibodies (scFv) were generated from sheep with Johne's disease by cloning heavy-chain and lambda light-chain variable regions and expressing these in fusion with gene III of filamentous phages. Two scFv clones (designated SurfS1.2 and SurfS2.2) were shown to be immunoreactive against M. avium subsp. paratuberculosis surface targets by flow cytometry, and immunoblotting identified specificity for a 34-kDa proteinase-susceptible determinant. Both antibodies were cross-reactive against Mycobacterium avium subsp. avium but nonreactive against Mycobacterium bovis or Mycobacterium phlei cells and were shown to be capable of enriching M. avium subsp. paratuberculosis cells by a factor of approximately 10(6)-fold when employed in magnetic bead separation of mixed Mycobacterium sp. cultures. Further, magnetic bead separation using SurfS1.2 and SurfS2.2 was capable of isolating as few as 10(3) M. avium subsp. paratuberculosis cells from ovine fecal samples, indicating the diagnostic potential of these reagents. Finally, inclusion of SurfS1.2 or SurfS2.2 in in vitro broth culture with M. avium subsp. paratuberculosis indicated that surface binding activity did not impede bacterial growth, although colony clumping was prevented. These results are discussed in terms of the potential use of single-chain phage display monoclonal antibodies as novel diagnostic reagents.",,"['Berger, Sven', 'Hinz, Dominik', 'Bannantine, John P.', 'Griffin, J. Frank T.']",,,,
,PMC,Tracking the spread of infectious disease: Two networks prove the power of international collaboration,http://dx.doi.org/10.1038/sj.embor.7400797,PMC1559678,,,,,"Ross, Karen",,,,
,PMC,Detection and Characterization of Bovine Coronaviruses in Fecal Specimens of Adult Cattle with Diarrhea during the Warmer Seasons,http://dx.doi.org/10.1128/JCM.02667-05,PMC1594715,,,"Bovine coronavirus (BCoV) is an etiological agent associated with winter dysentery (WD), prevalent in adult cattle during the winter. Although we previously detected, isolated, and characterized BCoV strains from adult cattle with WD (WD-BCoV strains) during the winter in South Korea, the precise epidemiology, as well as the causative agent of diarrhea in adult cattle in the warmer seasons, has not been examined. We examined 184 diarrheic fecal specimens collected from 75 herds of adult cattle from seven provinces during the spring (warm), autumn (warm), and summer (hot) seasons. Bovine coronavirus-positive reactions were detected for 107 (58.2%) diarrheic fecal samples (in 47/75 herds). Of these 107 positive samples, 90 fecal samples from 33 herds tested positive for BCoV alone and 17 fecal samples from 14 herds also tested positive for other pathogens. Biological comparisons between the 9 BCoV strains isolated in this study and the 10 previously isolated WD-BCoV strains revealed that there was no receptor-destroying enzyme (RDE) activity against mouse erythrocytes in the 9 BCoV strains but the 10 WD-BCoV strains had high RDE activity. Phylogenetic analysis of the spike (S) and hemagglutinin/esterase (HE) proteins revealed that all the Korean BCoVs clustered together regardless of season and were distinct from the other known BCoVs, suggesting a distinct evolutionary pathway for the Korean BCoVs. These and previous results revealed a high prevalence and widespread geographical distribution of BCoV, suggesting that this virus is endemic in adult cattle with diarrhea in all seasons in South Korea.",,"['Park, Su-Jin', 'Jeong, Cheol', 'Yoon, Soon-Seek', 'Choy, Hyoun E.', 'Saif, Linda J.', 'Park, Sung-Hee', 'Kim, You-Jung', 'Jeong, Jae-Ho', 'Park, Sang-Ik', 'Kim, Ha-Hyun', 'Lee, Bong-Joo', 'Cho, Ho-Seong', 'Kim, Sang-Ki', 'Kang, Mun-Il', 'Cho, Kyoung-Oh']",,,,
,PMC,An Oligonucleotide Microarray for High-Throughput Sequencing of the Mitochondrial Genome,http://dx.doi.org/10.2353/jmoldx.2006.060008,PMC1867623,,,"Previously we developed an oligonucleotide sequencing microarray (MitoChip) as an array-based sequencing platform for rapid and high-throughput analysis of mitochondrial DNA. The first generation MitoChip, however, was not tiled with probes for the noncoding D-loop region, a site frequently mutated in human cancers. Here we report the development of a second-generation MitoChip (v2.0) with oligonucleotide probes to sequence the entire mitochondrial genome. In addition, the MitoChip v2.0 contains redundant tiling of sequences for 500 of the most common haplotypes including single-nucleotide changes, insertions, and deletions. Sequencing results from 14 primary head and neck tumor tissues demonstrated that the v2.0 MitoChips detected a larger number of variants than the original version. Multiple coding region variants detected only in the second generation MitoChips, but not the earlier chip version, were further confirmed with conventional sequencing. Moreover, 31 variations in noncoding region were identified using MitoChips v2.0. Replicate experiments demonstrated >99.99% reproducibility in the second generation MitoChip. In seven head and neck cancer samples with matched lymphocyte DNA, the MitoChip v2.0 detected at least one cancer-associated mitochondrial mutation in four (57%) samples. These results indicate that the second generation MitoChip is a high-throughput platform for identification of mitochondrial DNA mutations in primary tumors.",,"['Zhou, Shaoyu', 'Kassauei, Keyaunoosh', 'Cutler, David J.', 'Kennedy, Giulia C.', 'Sidransky, David', 'Maitra, Anirban', 'Califano, Joseph']",,,,
,PMC,Extremely Low Exposure of a Community to Severe Acute Respiratory Syndrome Coronavirus: False Seropositivity due to Use of Bacterially Derived Antigens,http://dx.doi.org/10.1128/JVI.00649-06,PMC1563915,,,"Estimates of seropositivity to a new infectious agent in a community are useful to public health. For severe acute respiratory syndrome (SARS), the figures are conflicting. Herein, we screened 12,000 people in a community stricken by SARS 10 months previously and found 53 individuals (0.44%) who had immunoglobulin G antibodies to the SARS coronavirus (SARS-CoV) nucleocapsid (N) produced in bacteria. However, only seven of these (group 1) had sera which also reacted with the native N antigen expressed in SARS-CoV-infected Vero cells, N-transfected 293T cells, and tissues of infected SARS patients. Of these, six individuals had had SARS previously. The remaining person, as well as the 46 other individuals (group 2), were healthy and had no history of SARS. Group 1 antibodies recognized epitopes located slightly differently in N from those of group 2 antibodies, and a mouse hybridoma antibody resembling the former type was generated. Unusually, group 2 antibodies appeared to recognize cross-reactive bacterial epitopes that presumably were posttranslationally modified in eukaryotes and hence were probably not induced by SARS-CoV or related coronaviruses but rather by bacteria. The N antigen is thus highly unique. The extremely low rate (0.008%) of asymptomatic SARS infection found attests to the high virulence of the SARS-CoV virus.",,"['Leung, D. T. M.', 'van Maren, W. W. C.', 'Chan, F. K. L.', 'Chan, W. S.', 'Lo, A. W. I.', 'Ma, C. H.', 'Tam, F. C. H.', 'To, K. F.', 'Chan, P. K. S.', 'Sung, J. J. Y.', 'Lim, P. L.']",,,,
,PMC,Transcriptional Profiling Reveals a Possible Role for the Timing of the Inflammatory Response in Determining Susceptibility to a Viral Infection,http://dx.doi.org/10.1128/JVI.00929-06,PMC1563900,,,"Using a novel cDNA microarray prepared from sources of actively responding immune system cells, we have investigated the changes in gene expression in the target tissue during the early stages of infection of neonatal chickens with infectious bursal disease virus. Infections of two lines of chickens previously documented as genetically resistant and sensitive to infection were compared in order to ascertain early differences in the response to infection that might provide clues to the mechanism of differential genetic resistance. In addition to major changes that could be explained by previously described changes in infected tissue, some differences in gene expression on infection, and differences between the two chicken lines, were observed that led to a model for resistance in which a more rapid inflammatory response and more-extensive p53-related induction of apoptosis in the target B cells might limit viral replication and consequent pathology. Ironically, the effect in the asymptomatic neonatal infection is that more-severe B-cell depletion is seen in the more genetically resistant chicken. Changes of expression of many chicken genes of unknown function, indicating possible roles in the response to infection, may aid in the functional annotation of these genes.",,"['Ruby, Thomas', 'Whittaker, Catherine', 'Withers, David R.', 'Chelbi-Alix, Mounira K.', 'Morin, Veronique', 'Oudin, Anne', 'Young, John R.', 'Zoorob, Rima']",,,,
,PMC,Modulation of the Unfolded Protein Response by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein,http://dx.doi.org/10.1128/JVI.00659-06,PMC1563899,,,"Perturbation of the function of endoplasmic reticulum (ER) causes stress leading to the activation of cell signaling pathways known as the unfolded protein response (UPR). Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) uses ER as a site for synthesis and processing of viral proteins. In this report, we demonstrate that infection with SARS-CoV induces the UPR in cultured cells. A comparison with M, E, and NSP6 proteins indicates that SARS-CoV spike (S) protein sufficiently induces transcriptional activation of several UPR effectors, including glucose-regulated protein 78 (GRP78), GRP94, and C/EBP homologous protein. A substantial amount of S protein accumulates in the ER. The expression of S protein exerts different effects on the three major signaling pathways of the UPR. Particularly, it induces GRP78/94 through PKR-like ER kinase but has no influence on activating transcription factor 6 or X box-binding protein 1. Taken together, our findings suggest that SARS-CoV S protein specifically modulates the UPR to facilitate viral replication.",,"['Chan, Ching-Ping', 'Siu, Kam-Leung', 'Chin, King-Tung', 'Yuen, Kwok-Yung', 'Zheng, Bojian', 'Jin, Dong-Yan']",,,,
,PMC,Highly Conserved Regions within the Spike Proteins of Human Coronaviruses 229E and NL63 Determine Recognition of Their Respective Cellular Receptors,http://dx.doi.org/10.1128/JVI.00560-06,PMC1563880,,,"We have recently demonstrated that the severe acute respiratory syndrome coronavirus (SARS-CoV) receptor angiotensin converting enzyme 2 (ACE2) also mediates cellular entry of the newly discovered human coronavirus (hCoV) NL63. Here, we show that expression of DC-SIGN augments NL63 spike (S)-protein-driven infection of susceptible cells, while only expression of ACE2 but not DC-SIGN is sufficient for entry into nonpermissive cells, indicating that ACE2 fulfills the criteria of a bona fide hCoV-NL63 receptor. As for SARS-CoV, murine ACE2 is used less efficiently by NL63-S for entry than human ACE2. In contrast, several amino acid exchanges in human ACE2 which diminish SARS-S-driven entry do not interfere with NL63-S-mediated infection, suggesting that SARS-S and NL63-S might engage human ACE2 differentially. Moreover, we observed that NL63-S-driven entry was less dependent on a low-pH environment and activity of endosomal proteases compared to infection mediated by SARS-S, further suggesting differences in hCoV-NL63 and SARS-CoV cellular entry. NL63-S does not exhibit significant homology to SARS-S but is highly related to the S-protein of hCoV-229E, which enters target cells by engaging CD13. Employing mutagenic analyses, we found that the N-terminal unique domain in NL63-S, which is absent in 229E-S, does not confer binding to ACE2. In contrast, the highly homologous C-terminal parts of the NL63-S1 and 229E-S1 subunits in conjunction with distinct amino acids in the central regions of these proteins confer recognition of ACE2 and CD13, respectively. Therefore, despite the high homology of these sequences, they likely form sufficiently distinct surfaces, thus determining receptor specificity.",,"['Hofmann, Heike', 'Simmons, Graham', 'Rennekamp, Andrew J.', 'Chaipan, Chawaree', 'Gramberg, Thomas', 'Heck, Elke', 'Geier, Martina', 'Wegele, Anja', 'Marzi, Andrea', 'Bates, Paul', 'Pöhlmann, Stefan']",,,,
,PMC,Structural and Functional Basis for ADP-Ribose and Poly(ADP-Ribose) Binding by Viral Macro Domains,http://dx.doi.org/10.1128/JVI.00713-06,PMC1563857,,,"Macro domains constitute a protein module family found associated with specific histones and proteins involved in chromatin metabolism. In addition, a small number of animal RNA viruses, such as corona- and toroviruses, alphaviruses, and hepatitis E virus, encode macro domains for which, however, structural and functional information is extremely limited. Here, we characterized the macro domains from hepatitis E virus, Semliki Forest virus, and severe acute respiratory syndrome coronavirus (SARS-CoV). The crystal structure of the SARS-CoV macro domain was determined at 1.8-Å resolution in complex with ADP-ribose. Information derived from structural, mutational, and sequence analyses suggests a close phylogenetic and, most probably, functional relationship between viral and cellular macro domain homologs. The data revealed that viral macro domains have relatively poor ADP-ribose 1""-phosphohydrolase activities (which were previously proposed to be their biologically relevant function) but bind efficiently free and poly(ADP-ribose) polymerase 1-bound poly(ADP-ribose) in vitro. Collectively, these results suggest to further evaluate the role of viral macro domains in host response to viral infection.",,"['Egloff, Marie-Pierre', 'Malet, Hélène', 'Putics, Ákos', 'Heinonen, Maarit', 'Dutartre, Hélène', 'Frangeul, Antoine', 'Gruez, Arnaud', 'Campanacci, Valérie', 'Cambillau, Christian', 'Ziebuhr, John', 'Ahola, Tero', 'Canard, Bruno']",,,,
,PMC,The Fourth Pillar of the Framework Convention on Tobacco Control: Harm Reduction and the International Human Right to Health,,PMC1564445,,,,,"['Meier, Benjamin Mason', 'Shelley, Donna']",,,,
,PMC,Recommendations for the management of cough in adults,http://dx.doi.org/10.1136/thx.2006.065144,PMC2080754,,,,,"['Morice, A H', 'McGarvey, L', 'Pavord, I']",,,,
,PMC,Differential Expression of Neuronal ACE2 in Transgenic Mice with Overexpression of the Brain Renin-angiotensin System,http://dx.doi.org/10.1152/ajpregu.00292.2006,PMC1761128,,,"ACE2 is a newly discovered carboxy-peptidase responsible for the formation of vasodilatory peptides such as angiotensin-(1-7). We hypothesized that ACE2 is part of the brain renin-angiotensin system (RAS) and its expression regulated by the other elements of this system. ACE2 immuno-staining was performed in transgenic mouse brain sections from NSE-AT(1A) (overexpressing AT (1A) receptors), R(+)A(+) (overexpressing angiotensinogen, and renin) and control (non transgenic littermates) mice. Results show that ACE2 staining is widely distributed throughout the brain. Using cell type-specific antibodies, we observed that ACE2 staining is present in the cytoplasm of neuronal cell bodies but not in glial cells. In the subfornical organ, an area lacking the blood brain barrier and sensitive to blood borne angiotensin-II, ACE2 was significantly increased in transgenic mice. Interestingly, ACE2 mRNA and protein expression were inversely correlated in the nucleus of tractus solitarius/dorsal motor nucleus of the vagus and the ventrolateral medulla, when comparing transgenic to non-transgenic mice. These results suggest that ACE2 is localized to the cytoplasm of neuronal cells in the brain, and that ACE2 levels appear highly regulated by other components of the RAS, confirming its involvement in this system. Moreover, ACE2 expression in brain structures involved in the control of cardiovascular function suggests that the carboxypeptidase may have a role in the central regulation of blood pressure and diseases involving the autonomic nervous system such as hypertension.",,"['Doobay, Marc F.', 'Talman, Lauren S.', 'Obr, Teresa D.', 'Tian, Xin', 'Davisson, Robin L.', 'Lazartigues, Eric']",,,,
,PMC,Detection of Severe Acute Respiratory Syndrome Coronavirus in Stool Specimens by Commercially Available Real-Time Reverse Transcriptase PCR Assays,http://dx.doi.org/10.1128/JCM.01202-06,PMC1698307,,,"Three commercially available real-time reverse transcriptase PCR assays (the Artus RealArt HPA coronavirus LightCycler, the Artus RealArt HPA coronavirus Rotor-Gene, and the EraGen severe acute respiratory syndrome coronavirus POL assay) and three RNA extraction methodologies were evaluated for the detection of severe acute respiratory syndrome coronavirus RNA from 91 stool specimens. The assays' sensitivities were highest (58% to 75%) for specimens obtained 8 to 21 days after symptom onset. The assays were less sensitive when specimens were obtained less than 8 days or more than 21 days after the onset of symptoms. All assays were 100% specific.",,"['Louie, L.', 'Simor, A. E.', 'Chong, S.', 'Luinstra, K.', 'Petrich, A.', 'Mahony, J.', 'Smieja, M.', 'Johnson, G.', 'Gharabaghi, F.', 'Tellier, R.', 'Willey, B. M.', 'Poutanen, S.', 'Mazzulli, T.', 'Broukhanski, G.', 'Jamieson, F.', 'Louie, M.', 'Richardson, S.', None]",,,,
,PMC,C-E1 Fusion Protein Synthesized by Rubella Virus DI RNAs Maintained During Serial Passage,http://dx.doi.org/10.1016/j.virol.2006.07.041,PMC2694048,,,"Rubella virus (RUB) replicons are derivatives of the RUB infectious cDNA clone that retain the nonstructural open reading frame (NS-ORF) that encodes the replicase proteins but not the structural protein ORF (SP-ORF) that encodes the virion proteins. RUB defective interfering (DI) RNAs contain deletions within the SP-ORF and thus resemble replicons. DI RNAs often retain the 5′ end of the capsid protein (C) gene which has been shown to modulate virus-specific RNA synthesis. However, when replicons either with or without the C gene were passaged serially in the presence of wt RUB as a source of the virion proteins, it was found that neither replicon was maintained and DI RNAs were generated. The majority DI RNA species contained in-frame deletions in the SP-ORF leading to a fusion between the 5′ end of the C gene and the 3′ end of the E1 glycoprotein gene. DI infectious cDNA clones were constructed and transcripts from these DI infectious cDNA clones were maintained during serial passage with wt RUB. The C-E1 fusion protein encoded by the DI RNAs was synthesized and was required for maintenance of the DI RNA during serial passage. This is the first report of a functional novel gene product resulting from deletion during DI RNA generation. Thus far, the role of the C-E1 fusion protein in maintenance of DI RNAs during serial passage remained elusive as it was found that the fusion protein diminished rather than enhanced DI RNA synthesis and was not incorporated into virus particles.",,"['Tzeng, Wen-Pin', 'Frey, Teryl K.']",,,,
,PMC,"Structure of aminopeptidase N from Escherichia coli suggests a compartmentalized, gated active site",http://dx.doi.org/10.1073/pnas.0606167103,PMC1569165,,,"Aminopeptidase N from Escherichia coli is a major metalloprotease that participates in the controlled hydrolysis of peptides in the proteolytic pathway. Determination of the 870-aa structure reveals that it has four domains similar to the tricorn-interacting factor F3. The thermolysin-like active site is enclosed within a large cavity with a volume of 2,200 Å(3), which is inaccessible to substrates except for a small opening of approximately 8–10 Å. The substrate-based inhibitor bestatin binds to the protein with minimal changes, suggesting that this is the active form of the enzyme. The previously described structure of F3 had three distinct conformations that were described as “closed,” “intermediate,” and “open.” The structure of aminopeptidase N from E. coli, however, is substantially more closed than any of these. Taken together, the results suggest that these proteases, which are involved in intracellular peptide degradation, prevent inadvertent hydrolysis of inappropriate substrates by enclosing the active site within a large cavity. There is also some evidence that the open form of the enzyme, which admits substrates, remains inactive until it adopts the closed form.",,"['Addlagatta, Anthony', 'Gay, Leslie', 'Matthews, Brian W.']",,,,
,PMC,"Synergistic effect of a novel oxymatrine-baicalin combination against hepatitis B virus replication, α smooth muscle actin expression and type I collagen synthesis in vitro",http://dx.doi.org/10.3748/wjg.v12.i32.5153,PMC4088012,,,"AIM: To study the effect of oxymatrine-baicalin combination (OB) against HBV replication in 2.2.15 cells and α smooth muscle actin (α SMA) expression, type I, collagen synthesis in HSC-T6 cells. METHODS: The 2.2.15 cells and HSC-T6 cells were cultured and treated respectively. HBsAg and HBeAg in the culture supernatants were detected by ELISA and HBV DNA levels were determined by fluorescence quantitative PCR. Total RNA was extracted from HSC-T6 cells and reverse transcribed into cDNA. The cDNAs were amplified by PCR and the quantities were expressed in proportion to β actin. The total cellular proteins extracted from HSC-T6 cells were separated by electrophoresis. Resolved proteins were electrophoretically transferred to nitrocellulose membrane. Protein bands were revealed and the quantities were corrected by β actin. RESULTS: In the 2.2.15 cell culture system, the inhibitory rate against secretion of HBsAg and HBeAg in the OB group was significantly stronger than that in the oxymatrine group (HBsAg, P = 0.043; HBeAg, P = 0.026; respectively); HBV DNA level in the OB group was significantly lower than that in the oxymatrine group (P = 0.041). In HSC-T6 cells the mRNA and protein expression levels of α SMA in the OB group were significantly lower as compared with those in the oxymatrine group (mRNA, P = 0.013; protein, P = 0.042; respectively); The mRNA and protein expression levels of type I collagen in the OB group were significantly lower as compared with those in the oxymatrine group (mRNA, P < 0.01; protein, P < 0.01; respectively). CONCLUSION: OB combination has a better effect against HBV replication in 2.2.15 cells and is more effective against α SMA expression and typeI collagen synthesis in HSC-T6 cells than oxymatrine in vitro.",,"['Cheng, Yang', 'Ping, Jian', 'Xu, Huai-Dong', 'Fu, Hai-Jun', 'Zhou, Zhao-Hui']",,,,
,PMC,Real-time epidemic forecasting for pandemic influenza,http://dx.doi.org/10.1017/S0950268806007084,PMC2870596,,,"The ongoing worldwide spread of the H5N1 influenza virus in birds has increased concerns of a new human influenza pandemic and a number of surveillance initiatives are planned, or are in place, to monitor the impact of a pandemic in near real-time. Using epidemiological data collected during the early stages of an outbreak, we show how the timing of the maximum prevalence of the pandemic wave, along with its amplitude and duration, might be predicted by fitting a mass-action epidemic model to the surveillance data by standard regression analysis. This method is validated by applying the model to routine data collected in the United Kingdom during the different waves of the previous three pandemics. The success of the method in forecasting historical prevalence suggests that such outbreaks conform reasonably well to the theoretical model, a factor which may be exploited in a future pandemic to update ongoing planning and response.",,"['HALL, I.\xa0M.', 'GANI, R.', 'HUGHES, H.\xa0E.', 'LEACH, S.']",,,,
,PMC,Rethinking Global Health Training in North America,,PMC1781309,,,,,"['Gupta, Rajesh', 'Hotez, Peter']",,,,
,PMC,A Contemporary View of Coronavirus Transcription,http://dx.doi.org/10.1128/JVI.01358-06,PMC1797243,,,,,"['Sawicki, Stanley G.', 'Sawicki, Dorothea L.', 'Siddell, Stuart G.']",,,,
,PMC,Generation and Analysis of Infectious Virus-Like Particles of Uukuniemi Virus (Bunyaviridae): a Useful System for Studying Bunyaviral Packaging and Budding,http://dx.doi.org/10.1128/JVI.01362-06,PMC1641803,,,"In the present report we describe an infectious virus-like particle (VLP) system for the Uukuniemi (UUK) virus, a member of the Bunyaviridae family. It utilizes our recently developed reverse genetic system based on the RNA polymerase I minigenome system for UUK virus used to study replication, encapsidation, and transcription by monitoring reporter gene expression. Here, we have added the glycoprotein precursor expression plasmid together with the minigenome, nucleoprotein, and polymerase to generate VLPs, which incorporate the minigenome and are released into the supernatant. The particles are able to infect new cells, and reporter gene expression can be monitored if the trans-acting viral proteins (RNA polymerase and nucleoprotein) are also expressed in these cells. No minigenome transfer occurred in the absence of glycoproteins, demonstrating that the glycoproteins are absolutely required for the generation of infectious particles. Moreover, expression of glycoproteins alone was sufficient to produce and release VLPs. We show that the ribonucleoproteins (RNPs) are incorporated into VLPs but are not required for the generation of particles. Morphological analysis of the particles by electron microscopy revealed that VLPs, either with or without minigenomes, display a surface morphology indistinguishable from that of the authentic UUK virus and that they bud into Golgi vesicles in the same way as UUK virus does. This infectious VLP system will be very useful for studying the bunyaviral structural components required for budding and packaging of RNPs and receptor binding and may also be useful for the development of new vaccines for the human pathogens from this family.",,"['Överby, Anna K.', 'Popov, Vsevolod', 'Neve, Etienne P. A.', 'Pettersson, Ralf F.']",,,,
,PMC,Construction of a Severe Acute Respiratory Syndrome Coronavirus Infectious cDNA Clone and a Replicon To Study Coronavirus RNA Synthesis,http://dx.doi.org/10.1128/JVI.00385-06,PMC1641757,,,"The engineering of a full-length infectious cDNA clone and a functional replicon of the severe acute respiratory syndrome coronavirus (SARS-CoV) Urbani strain as bacterial artificial chromosomes (BACs) is described in this study. In this system, the viral RNA was expressed in the cell nucleus under the control of the cytomegalovirus promoter and further amplified in the cytoplasm by the viral replicase. Both the infectious clone and the replicon were fully stable in Escherichia coli. Using the SARS-CoV replicon, we have shown that the recently described RNA-processing enzymes exoribonuclease, endoribonuclease, and 2′-O-ribose methyltransferase were essential for efficient coronavirus RNA synthesis. The SARS reverse genetic system developed as a BAC constitutes a useful tool for the study of fundamental viral processes and also for developing genetically defined vaccines.",,"['Almazán, Fernando', 'DeDiego, Marta L.', 'Galán, Carmen', 'Escors, David', 'Álvarez, Enrique', 'Ortego, Javier', 'Sola, Isabel', 'Zuñiga, Sonia', 'Alonso, Sara', 'Moreno, Jose L.', 'Nogales, Aitor', 'Capiscol, Carmen', 'Enjuanes, Luis']",,,,
,PMC,"Rotavirus Activates JNK and p38 Signaling Pathways in Intestinal Cells, Leading to AP-1-Driven Transcriptional Responses and Enhanced Virus Replication",http://dx.doi.org/10.1128/JVI.00390-06,PMC1641755,,,"Rotavirus infection is known to regulate transcriptional changes in many cellular genes. The transcription factors NF-κB and AP-1 are activated by rotavirus infection, but the upstream processes leading to these events are largely unidentified. We therefore studied the activation state during rotavirus infection of c-Jun NH(2)-terminal kinase (JNK) and p38, which are kinases known to activate AP-1. As assessed by Western blotting using phospho-specific antibodies, infection with rhesus rotavirus (RRV) or exposure to UV-psoralen-inactivated RRV (I-RRV) resulted in the activation of JNK in HT-29, Caco-2, and MA104 cells. Activation of p38 during RRV infection was observed in Caco-2 and MA104 cells but not in HT-29 cells, whereas exposure to I-RRV did not lead to p38 activation in these cell lines. Rotavirus strains SA11, CRW-8, Wa, and UK also activated JNK and p38. Consistent with the activation of JNK, a corresponding increase in the phosphorylation of the AP-1 component c-Jun was shown. The interleukin-8 (IL-8) and c-jun promoters contain AP-1 binding sequences, and these genes have been shown previously to be transcriptionally up-regulated during rotavirus infection. Using specific inhibitors of JNK (SP600125) and p38 (SB203580) and real-time PCR, we showed that maximal RRV-induced IL-8 and c-jun transcription required JNK and p38 activity. This highlights the importance of JNK and p38 in RRV-induced, AP-1-driven gene expression. Significantly, inhibition of p38 or JNK in Caco-2 cells reduced RRV growth but not viral structural antigen expression, demonstrating the potential importance of JNK and p38 activation for optimal rotavirus replication.",,"['Holloway, Gavan', 'Coulson, Barbara S.']",,,,
,PMC,What we have learnt from SARS epidemics in China,,PMC1550436,,,"China's experience with SARS has important implications worldwide, and may improve preparedness for an epidemic if bird flu spreads to humans",,"['Zhong, Nanshan', 'Zeng, Guangqiao']",,,,
,PMC,What is new in the nucleolus?: Workshop on the Nucleolus: New Perspectives,http://dx.doi.org/10.1038/sj.embor.7400786,PMC1559673,,,,,"['Matthews, David A', 'Olson, Mark O.J']",,,,
,PMC,Putative cis-Acting Stem-Loops in the 5′ Untranslated Region of the Severe Acute Respiratory Syndrome Coronavirus Can Substitute for Their Mouse Hepatitis Virus Counterparts,http://dx.doi.org/10.1128/JVI.00455-06,PMC1641749,,,"Consensus covariation-based secondary structural models for the 5′ 140 nucleotides of the 5′ untranslated regions (5′UTRs) from mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SCoV) were developed and predicted three major helical stem-loop structures, designated stem-loop 1 (SL1), SL2, and SL4. The SCoV 5′UTR was predicted to contain a fourth stem-loop, named SL3, in which the leader transcriptional regulatory sequence (TRS) is folded into a hairpin loop. cDNAs corresponding to MHV/SCoV chimeric genomes were constructed by replacing the complete MHV 5′UTR with the corresponding SCoV sequence and by separately replacing MHV 5′UTR putative SL1, putative SL2, TRS, and putative SL4 with the corresponding SCoV sequences. Chimeric genomes were transcribed in vitro, and viruses were recovered after electroporation into permissive cells. Genomes in which the MHV 5′UTR SL1, SL2, and SL4 were individually replaced by their SCoV counterparts were viable. Chimeras containing the complete SCoV 5′UTR or the predicted SCoV SL3 were not viable. A chimera containing the SCoV 5′UTR in which the SCoV TRS was replaced with the MHV TRS was also not viable. The chimera containing the entire SCoV 5′UTR failed to direct the synthesis of any virus-specific RNA. Replacing the SCoV TRS with the MHV TRS in the MHV/5′UTR SCoV chimera permitted the synthesis of minus-sense genome-sized RNA but did not support the production of positive- or minus-sense subgenomic RNA7. A similar phenotype was obtained with the MHV/SCoV SL3 chimera. These results suggest a role for the TRS in the replication of minus-sense genomic RNA in addition to its known function in subgenomic RNA synthesis.",,"['Kang, Hyojeung', 'Feng, Min', 'Schroeder, Megan E.', 'Giedroc, David P.', 'Leibowitz, Julian L.']",,,,
,PMC,Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradation,http://dx.doi.org/10.1073/pnas.0603144103,PMC1568942,,,"Severe acute respiratory syndrome (SARS) coronavirus (SCoV) causes a recently emerged human disease associated with pneumonia. The 5′ end two-thirds of the single-stranded positive-sense viral genomic RNA, gene 1, encodes 16 mature proteins. Expression of nsp1, the most N-terminal gene 1 protein, prevented Sendai virus-induced endogenous IFN-β mRNA accumulation without inhibiting dimerization of IFN regulatory factor 3, a protein that is essential for activation of the IFN-β promoter. Furthermore, nsp1 expression promoted degradation of expressed RNA transcripts and host endogenous mRNAs, leading to a strong host protein synthesis inhibition. SCoV replication also promoted degradation of expressed RNA transcripts and host mRNAs, suggesting that nsp1 exerted its mRNA destabilization function in infected cells. In contrast to nsp1-induced mRNA destablization, no degradation of the 28S and 18S rRNAs occurred in either nsp1-expressing cells or SCoV-infected cells. These data suggested that, in infected cells, nsp1 promotes host mRNA degradation and thereby suppresses host gene expression, including proteins involved in host innate immune functions. SCoV nsp1-mediated promotion of host mRNA degradation may play an important role in SCoV pathogenesis.",,"['Kamitani, Wataru', 'Narayanan, Krishna', 'Huang, Cheng', 'Lokugamage, Kumari', 'Ikegami, Tetsuro', 'Ito, Naoto', 'Kubo, Hideyuki', 'Makino, Shinji']",,,,
,PMC,Role for primary care in epidemic surge capacity,,PMC1781506,,,,,"Mazowita, G.",,,,
,PMC,The structure of the endoribonuclease XendoU: From small nucleolar RNA processing to severe acute respiratory syndrome coronavirus replication,http://dx.doi.org/10.1073/pnas.0602426103,PMC1567885,,,"Small nucleolar RNAs (snoRNAs) play a key role in eukaryotic ribosome biogenesis. In most cases, snoRNAs are encoded in introns and are released through the splicing reaction. Some snoRNAs are, instead, produced by an alternative pathway consisting of endonucleolytic processing of pre-mRNA. XendoU, the endoribonuclease responsible for this activity, is a U-specific, metal-dependent enzyme that releases products with 2′–3′ cyclic phosphate termini. XendoU is broadly conserved among eukaryotes, and it is a genetic marker of nidoviruses, including the severe acute respiratory syndrome coronavirus, where it is essential for replication and transcription. We have determined by crystallography the structure of XendoU that, by refined search methodologies, appears to display a unique fold. Based on sequence conservation, mutagenesis, and docking simulations, we have identified the active site. The conserved structural determinants of this site may provide a framework for attempting to design antiviral drugs to interfere with the infectious nidovirus life cycle.",,"['Renzi, Fabiana', 'Caffarelli, Elisa', 'Laneve, Pietro', 'Bozzoni, Irene', 'Brunori, Maurizio', 'Vallone, Beatrice']",,,,
,PMC,Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release,http://dx.doi.org/10.1073/pnas.0605402103,PMC1567914,,,"Fourteen ORFs have been identified in the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) genome. ORF 3a of SARS-CoV codes for a recently identified transmembrane protein, but its function remains unknown. In this study we confirmed the 3a protein expression and investigated its localization at the surface of SARS-CoV-infected or 3a-cDNA-transfected cells. Our experiments showed that recombinant 3a protein can form a homotetramer complex through interprotein disulfide bridges in 3a-cDNA-transfected cells, providing a clue to ion channel function. The putative ion channel activity of this protein was assessed in 3a-complement RNA-injected Xenopus oocytes by two-electrode voltage clamp. The results suggest that 3a protein forms a potassium sensitive channel, which can be efficiently inhibited by barium. After FRhK-4 cells were transfected with an siRNA, which is known to suppress 3a expression, followed by infection with SARS-CoV, the released virus was significantly decreased, whereas the replication of the virus in the infected cells was not changed. Our observation suggests that SARS-CoV ORF 3a functions as an ion channel that may promote virus release. This finding will help to explain the highly pathogenic nature of SARS-CoV and to develop new strategies for treatment of SARS infection.",,"['Lu, Wei', 'Zheng, Bo-Jian', 'Xu, Ke', 'Schwarz, Wolfgang', 'Du, Lanying', 'Wong, Charlotte K. L.', 'Chen, Jiadong', 'Duan, Shuming', 'Deubel, Vincent', 'Sun, Bing']",,,,
,PMC,Living Donor Renal Transplantation Using Alemtuzumab Induction and Tacrolimus Monotherapy,http://dx.doi.org/10.1111/j.1600-6143.2006.01495.x,PMC3154761,,,"Alemtuzumab was used as an induction agent in 205 renal transplant recipients undergoing 207 living donor renal transplants. All donor kidneys were recovered laparoscopically. Postoperatively, patients were treated with tacrolimus monotherapy, and immunosuppression was weaned when possible. Forty-seven recipients of living donor renal transplants prior to the induction era who received conventional triple drug immunosuppression without antibody induction served as historic controls. The mean follow-up was 493 days in the alemtuzumab group and 2101 days in the historic control group. Actuarial 1-year patient and graft survival were 98.6% and 98.1% in the alemtuzumab group, compared to 93.6% and 91.5% in the control group, respectively. The incidence of acute cellular rejection (ACR) at 1 year was 6.8% in the alemtuzumab group and 17.0% (p < 0.05) in the historic control group. Most (81.3%) episodes of ACR in the alemtuzumab group were Banff 1 (a or b) and were sensitive to steroid pulses for the treatment of rejection. There was no cytomegalovirus disease or infection. The incidence of delayed graft function was 0%, and the incidence of posttransplant insulin-dependent diabetes mellitus was 0.5%. This study represents the largest series to date of live donor renal transplant recipients undergoing alemtuzumab induction, and confirms the short-term safety and efficacy of this approach.",,"['Tan, H. P.', 'Kaczorowski, D. J.', 'Basu, A.', 'Unruh, M.', 'McCauley, J.', 'Wu, C.', 'Donaldson, J.', 'Dvorchik, I.', 'Kayler, L.', 'Marcos, A.', 'Randhawa, P.', 'Smetanka, C.', 'Starzl, T. E.', 'Shapiro, R.']",,,,
,PMC,Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: Engineering a recombination-resistant genome,http://dx.doi.org/10.1073/pnas.0605438103,PMC1531645,,,"Live virus vaccines provide significant protection against many detrimental human and animal diseases, but reversion to virulence by mutation and recombination has reduced appeal. Using severe acute respiratory syndrome coronavirus as a model, we engineered a different transcription regulatory circuit and isolated recombinant viruses. The transcription network allowed for efficient expression of the viral transcripts and proteins, and the recombinant viruses replicated to WT levels. Recombinant genomes were then constructed that contained mixtures of the WT and mutant regulatory circuits, reflecting recombinant viruses that might occur in nature. Although viable viruses could readily be isolated from WT and recombinant genomes containing homogeneous transcription circuits, chimeras that contained mixed regulatory networks were invariantly lethal, because viable chimeric viruses were not isolated. Mechanistically, mixed regulatory circuits promoted inefficient subgenomic transcription from inappropriate start sites, resulting in truncated ORFs and effectively minimize viral structural protein expression. Engineering regulatory transcription circuits of intercommunicating alleles successfully introduces genetic traps into a viral genome that are lethal in RNA recombinant progeny viruses.",,"['Yount, Boyd', 'Roberts, Rhonda S.', 'Lindesmith, Lisa', 'Baric, Ralph S.']",,,,
,PMC,Human Neutralizing Fab Molecules against Severe Acute Respiratory Syndrome Coronavirus Generated by Phage Display,http://dx.doi.org/10.1128/CVI.00037-06,PMC1539127,,,"Human recombinant Fab fragments specific for the spike protein of severe acute respiratory syndrome coronavirus (SARS-CoV) were screened from a human Fab library, which was generated from RNAs from peripheral lymphocytes of convalescent SARS patients. Among 50 randomly picked clones, 12 Fabs specially reacted with S protein by an enzyme-linked immunosorbent assay. The microneutralizing test showed that one clone, designated M1A, had neutralizing activity on Vero E6 cells against SARS-CoV. DNA sequence analysis indicated that the light- and heavy-chain genes of M1A Fab belong to the κ2a and 4f families, respectively. A neutralizing test on purified M1A demonstrated that 0.5 mg/ml of M1A completely inhibited SARS-CoV activity, with an absence of cytopathic effect for 7 days. Real-time fluorescence reverse transcription-PCR also proved the neutralizing capacity of M1A. These data showed that the number of virus copies was significantly reduced in the M1A-treated group, suggesting an important role for M1A in passive immunoprophylaxis against the SARS virus.",,"['Kang, Xiaoping', 'Yang, Bao-an', 'Hu, Yuyang', 'Zhao, Hui', 'Xiong, Wei', 'Yang, Yinhui', 'Si, Bingyin', 'Zhu, Qingyu']",,,,
,PMC,Vaccines: All Things Considered,http://dx.doi.org/10.1128/CVI.00152-06,PMC1539119,,,,,"['Rosenthal, Ken S.', 'Zimmerman, Daniel H.']",,,,
,PMC,Influenza Virus NS Vectors Expressing the Mycobacterium tuberculosis ESAT-6 Protein Induce CD4(+) Th1 Immune Response and Protect Animals against Tuberculosis Challenge,http://dx.doi.org/10.1128/CVI.00056-06,PMC1539114,,,"Infection with Mycobacterium tuberculosis remains a major cause of morbidity and mortality all over the world. Since the effectiveness of the only available tuberculosis vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is suboptimal, there is a strong demand to develop new tuberculosis vaccines. As tuberculosis is an airborne disease, the intranasal route of vaccination might be preferable. Live influenza virus vaccines might be considered as potential vectors for mucosal immunization against various viral or bacterial pathogens, including M. tuberculosis. We generated several subtypes of attenuated recombinant influenza A viruses expressing the 6-kDa early secretory antigenic target protein (ESAT-6) of M. tuberculosis from the NS1 reading frame. We were able to demonstrate the potency of influenza virus NS vectors to induce an M. tuberculosis-specific Th1 immune response in mice. Moreover, intranasal immunization of mice and guinea pigs with such vectors induced protection against mycobacterial challenge, similar to that induced by BCG vaccination.",,"['Sereinig, Sabine', 'Stukova, Marina', 'Zabolotnyh, Natalia', 'Ferko, Boris', 'Kittel, Christian', 'Romanova, Julia', 'Vinogradova, Tatiana', 'Katinger, Hermann', 'Kiselev, Oleg', 'Egorov, Andrej']",,,,
,PMC,Personal protective equipment for preventing respiratory infections: What have we really learned?,http://dx.doi.org/10.1503/cmaj.060685,PMC1513408,,,,,"Conly, John M.",,,,
,PMC,The Dr Family of E.coli Adhesins bind independently to the Decay-Accelerating Factor and the N-domain of Carcinoembryonic Antigen,http://dx.doi.org/10.1074/jbc.M605681200,PMC2629542,,,"Escherichia coli expressing the Dr family of adhesins adhere to epithelial cells by binding to decay-accelerating factor (DAF) and carcinoembryonic antigen (CEA)-related cell surface proteins. The attachment of bacteria expressing Dr adhesins to DAF induces clustering of DAF around bacterial cells, and also recruitment of CEA - related cell adhesion molecules. (CEA, CEACAM1, CEACAM3 and CEACAM6) have been shown to serve as receptors for some Dr adhesins (DraE, DaaE, and AfaE-III). We demonstrate that DraE, DaaE, AfaE-V and AfaE-I adhesins bind to the N-domain of CEA. We utilized binding analysis of naturally occuring Dr variants and constructed mutants, an nuclear magnetic resonance (NMR) analysis to identify the amino acids of DraE and CEA involved in binding interactions. We identified distinct binding sites for DAF and CEA on opposite faces of the adhesin. These findings imply that the adhesin could be bound simultaneously by both receptors on the epithelial cell surface. The occurrence at high frequency of point mutations in the amino acids of Dr adhesins involved in CEA binding indicate that interaction with these receptors play an important role in niche adaptation of E. coli expressing Dr adhesins.",,"['Korotkova, Natalia', 'Cota, Ernesto', 'Lebedin, Yuri', 'Monpouet, Severine', 'Guignot, Julie', 'Servin, Alan L.', 'Matthews, Steve', 'Moseley, Steve']",,,,
,PMC,Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4,http://dx.doi.org/10.1172/JCI26185,PMC1523410,,,"HIV-1 envelope glycoproteins (Env), expressed at the cell surface, induce apoptosis of uninfected CD4(+) T cells, contributing to the development of AIDS. Here we demonstrate that, independently of HIV replication, transfected or HIV-infected cells that express Env induced autophagy and accumulation of Beclin 1 in uninfected CD4(+) T lymphocytes via CXCR4. The same phenomena occurred in a T cell line and in transfected HEK.293 cells that expressed both wild-type CXCR4 and a truncated form of CD4 that is unable to bind the lymphocyte-specific protein kinase Lck. Env-mediated autophagy is required to trigger CD4(+) T cell apoptosis since blockade of autophagy at different steps, by either drugs (3-methyladenine and bafilomycin A1) or siRNAs specific for Beclin 1/Atg6 and Atg7 genes, totally inhibited the apoptotic process. Furthermore, CD4(+) T cells still underwent Env-mediated cell death with autophagic features when apoptosis was inhibited. These results suggest that HIV-infected cells can induce autophagy in bystander CD4(+) T lymphocytes through contact of Env with CXCR4, leading to apoptotic cell death, a mechanism most likely contributing to immunodeficiency.",,"['Espert, Lucile', 'Denizot, Mélanie', 'Grimaldi, Marina', 'Robert-Hebmann, Véronique', 'Gay, Bernard', 'Varbanov, Mihayl', 'Codogno, Patrice', 'Biard-Piechaczyk, Martine']",,,,
,PMC,Role of Metapneumovirus in Viral Respiratory Infections in Young Children,http://dx.doi.org/10.1128/JCM.00164-06,PMC1594650,,,"The contribution of human metapneumovirus (hMPV) relative to that of other respiratory viruses as a cause of respiratory infections in children less than 1 year old has been evaluated. From October 2003 to April 2004, nasopharyngeal samples from 211 children less than 1 year old were analyzed to detect respiratory viruses. Respiratory syncytial virus (RSV) was the predominant virus isolated (96 children [45.5%]), followed by influenza A virus, parainfluenza virus, adenovirus, cytomegalovirus, and herpes simplex virus type 1, which were only occasionally detected. From January 2004 to April 2004, a nested retrotranscription-PCR, using in-house primers directed to the matrix protein gene of hMPV, was carried out on samples in which no other viruses were detected. hMPV was detected in 18 (16.2%) children, indicating that this virus was the second-most-frequent cause of viral respiratory infections in children less than 1 year old. The rate of hospitalization for RSV- and hMPV-infected children was higher than 75%. While RSV had a peak from December to February, hMPV was increasingly detected from January to April. The mean age of hMPV-infected children (6.44 ± 3.64 [mean ± standard deviation] months) was significantly higher than that of RSV-infected children (3.99 ± 2.96 [mean ± standard deviation] months). On the other hand, 64.3% of the RSV-infected children and 12.5% of the hMPV-infected children showed high levels of C-reactive protein. Although several authors have reported that clinical symptoms of hMPV-positive patients mirrored those of RSV-positive patients, differences between the two viruses can be found.",,"['Ordás, José', 'Boga, José Antonio', 'Alvarez-Argüelles, Marta', 'Villa, Laura', 'Rodríguez-Dehli, Cristina', 'de Oña, María', 'Rodríguez, Julián', 'Melón, Santiago']",,,,
,PMC,Multicenter Comparison of Nucleic Acid Extraction Methods for Detection of Severe Acute Respiratory Syndrome Coronavirus RNA in Stool Specimens,http://dx.doi.org/10.1128/JCM.02460-05,PMC1594626,,,"The emergence of a novel coronavirus (CoV) as the cause of severe acute respiratory syndrome (SARS) catalyzed the development of rapid diagnostic tests. Stool samples have been shown to be appropriate for diagnostic testing for SARS CoV, although it has been recognized to be a heterogeneous and difficult sample that contains amplification inhibitors. Limited information on the efficiency of extraction methods for the purification and concentration of SARS CoV RNA from stool samples is available. Our study objectives were to determine the optimal extraction method for SARS CoV RNA detection and to examine the effect of increased specimen volume for the detection of SARS CoV RNA in stool specimens. We conducted a multicenter evaluation of four automated and four manual extraction methods using dilutions of viral lysate in replicate mock stool samples, followed by quantitation of SARS CoV RNA using real-time reverse transcriptase PCR. The sensitivities of the manual methods ranged from 50% to 100%, with the Cortex Biochem Magazorb method, a magnetic bead isolation method, allowing detection of all 12 positive samples. The sensitivities of the automated methods ranged from 75% to 100%. The bioMérieux NucliSens automated extractor and miniMag extraction methods each had a sensitivity of 100%. Examination of the copy numbers detected and the generation of 10-fold dilutions of the extracted material indicated that a number of extraction methods retained inhibitory substances that prevented optimal amplification. Increasing the volume of sample input did improve detection. This information could be useful for the extraction of other RNA viruses from stool samples and demonstrates the need to evaluate extraction methods for different specimen types.",,"['Petrich, A.', 'Mahony, J.', 'Chong, S.', 'Broukhanski, G.', 'Gharabaghi, F.', 'Johnson, G.', 'Louie, L.', 'Luinstra, K.', 'Willey, B.', 'Akhaven, P.', 'Chui, L.', 'Jamieson, F.', 'Louie, M.', 'Mazzulli, T.', 'Tellier, R.', 'Smieja, M.', 'Cai, W.', 'Chernesky, M.', 'Richardson, S. E.', None]",,,,
,PMC,Increasing Appearance of Reassortant Influenza B Virus in Taiwan from 2002 to 2005,http://dx.doi.org/10.1128/JCM.02694-05,PMC1594622,,,"Genetic and antigenic analyses of influenza B virus field strains isolated in Taiwan from 1998 to 2005 were performed. To investigate the molecular evolution of influenza B viruses, sequence analysis of the hemagglutinin (HA1 subunit) and neuraminidase genes was performed. All influenza B viruses isolated between 1998 and 2000 belonged to the B/Yamagata/16/88 lineage. The B/Victoria/2/87 lineage, which was cocirculating with the Yamagata lineage, was identified in Taiwan in March 2001. Concurrently, there was an increasing prevalence of this lineage in many parts of the world, including North America and Europe, during the 2001-2002 season. Since 2002, genetic reassortants of influenza B virus with the Victoria lineage of hemagglutinin and the Yamagata lineage of neuraminidase have been found at a rate of 46%. Therefore, in 2002, at least three sublineages of influenza B virus strains, the B/Shanghai/361/2002-like strain (Yamagata lineage), the B/Hong Kong/330/01-like strain (Victoria lineage), and the B/Hong Kong/1351/02-like strain (B reassortant lineage), were identified in Taiwan. The results showed that genetically distinct lineages can cocirculate in the population and that the reassortment among these strains plays a role in generating the genetic diversity of influenza B viruses. Interestingly, from January to April 2005, B reassortant viruses became dominant (73%) in Taiwan, which indicated that a mismatch had occurred between the influenza B vaccine strain recommended for the 2004-2005 season in the Northern hemisphere by the World Health Organization and the epidemic strain.",,"['Tsai, Huey-Pin', 'Wang, Hsuan-Chen', 'Kiang, David', 'Huang, Sheng-Wen', 'Kuo, Pin-Hwa', 'Liu, Ching-Chuan', 'Su, Ih-Jen', 'Wang, Jen-Ren']",,,,
,PMC,New Antiviral Target Revealed by the Hexameric Structure of Mouse Hepatitis Virus Nonstructural Protein nsp15,http://dx.doi.org/10.1128/JVI.00525-06,PMC1563835,,,"The unique coronavirus transcription/replication machinery comprised of multiple virus-encoded nonstructural proteins (nsp) plays a vital role during initial and intermediate phases of the viral life cycle. The crystal structure of mouse hepatitis virus strain A59 (MHV-A59) nsp15 is reported at 2.15-Å resolution. nsp15 is an XendoU endoribonuclease and is the first one from this family to have its structure unveiled. The MHV-A59 nsp15 monomer structure has a novel protein fold. Two nsp15 trimers form a back-to-back hexamer that is believed to be the functional unit. The structure reveals the catalytic site including the highly conserved residues His262, His277, and Lys317, which is supported by mutagenesis analysis. Gel filtration and enzyme activity assays confirmed that the hexamer is the active form for nsp15 and demonstrate the specificity of nsp15 for uridylate. The high sequence conservation of nsp15 in coronaviruses, including that of severe acute respiratory syndrome, suggests that this protein may provide a new target for the design of antiviral therapeutics.",,"['Xu, Xiaoling', 'Zhai, Yujia', 'Sun, Fei', 'Lou, Zhiyong', 'Su, Dan', 'Xu, Yuanyuan', 'Zhang, Rongguang', 'Joachimiak, Andrzej', 'Zhang, Xuejun C.', 'Bartlam, Mark', 'Rao, Zihe']",,,,
,PMC,Dodecamer Structure of Severe Acute Respiratory Syndrome Coronavirus Nonstructural Protein nsp10,http://dx.doi.org/10.1128/JVI.00483-06,PMC1563834,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) nonstructural proteins nsp1 to nsp16 have been implicated by genetic analysis in the assembly of a functional replication/transcription complex. We report the crystal structure of nsp10 from SARS-CoV at 2.1-Å resolution. The nsp10 structure has a novel fold, and 12 identical subunits assemble to form a unique spherical dodecameric architecture. Two zinc fingers have been identified from the nsp10 monomer structure with the sequence motifs C-(X)(2)-C-(X)(5)-H-(X)(6)-C and C-(X)(2)-C-(X)(7)-C-(X)-C. The nsp10 crystal structure is the first of a new class of zinc finger protein three-dimensional structures to be revealed experimentally. The zinc finger sequence motifs are conserved among all three coronavirus antigenic groups, implicating an essential function for nsp10 in all coronaviruses. Based on the structure, we propose that nsp10 is a transcription factor for coronavirus replication/transcription.",,"['Su, Dan', 'Lou, Zhiyong', 'Sun, Fei', 'Zhai, Yujia', 'Yang, Haitao', 'Zhang, Rongguang', 'Joachimiak, Andrzej', 'Zhang, Xuejun C.', 'Bartlam, Mark', 'Rao, Zihe']",,,,
,PMC,Supramolecular Architecture of Severe Acute Respiratory Syndrome Coronavirus Revealed by Electron Cryomicroscopy,http://dx.doi.org/10.1128/JVI.00645-06,PMC1563832,,,"Coronavirus particles are enveloped and pleomorphic and are thus refractory to crystallization and symmetry-assisted reconstruction. A novel methodology of single-particle image analysis was applied to selected virus features to obtain a detailed model of the oligomeric state and spatial relationships among viral structural proteins. Two-dimensional images of the S, M, and N structural proteins of severe acute respiratory syndrome coronavirus and two other coronaviruses were refined to a resolution of ∼4 nm. Proteins near the viral membrane were arranged in overlapping lattices surrounding a disordered core. Trimeric glycoprotein spikes were in register with four underlying ribonucleoprotein densities. However, the spikes were dispensable for ribonucleoprotein lattice formation. The ribonucleoprotein particles displayed coiled shapes when released from the viral membrane. Our results contribute to the understanding of the assembly pathway used by coronaviruses and other pleomorphic viruses and provide the first detailed view of coronavirus ultrastructure.",,"['Neuman, Benjamin W.', 'Adair, Brian D.', 'Yoshioka, Craig', 'Quispe, Joel D.', 'Orca, Gretchen', 'Kuhn, Peter', 'Milligan, Ronald A.', 'Yeager, Mark', 'Buchmeier, Michael J.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.01286-06,PMC1563793,,,,,,,,,
,PMC,Crystal Structure of Nonstructural Protein 10 from the Severe Acute Respiratory Syndrome Coronavirus Reveals a Novel Fold with Two Zinc-Binding Motifs,http://dx.doi.org/10.1128/JVI.00467-06,PMC1563791,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) possesses a large 29.7-kb positive-stranded RNA genome. The first open reading frame encodes replicase polyproteins 1a and 1ab, which are cleaved to generate 16 “nonstructural” proteins, nsp1 to nsp16, involved in viral replication and/or RNA processing. Among these, nsp10 plays a critical role in minus-strand RNA synthesis in a related coronavirus, murine hepatitis virus. Here, we report the crystal structure of SARS-CoV nsp10 at a resolution of 1.8 Å as determined by single-wavelength anomalous dispersion using phases derived from hexatantalum dodecabromide. nsp10 is a single domain protein consisting of a pair of antiparallel N-terminal helices stacked against an irregular β-sheet, a coil-rich C terminus, and two Zn fingers. nsp10 represents a novel fold and is the first structural representative of this family of Zn finger proteins found so far exclusively in coronaviruses. The first Zn finger coordinates a Zn(2+) ion in a unique conformation. The second Zn finger, with four cysteines, is a distant member of the “gag-knuckle fold group” of Zn(2+)-binding domains and appears to maintain the structural integrity of the C-terminal tail. A distinct clustering of basic residues on the protein surface suggests a nucleic acid-binding function. Gel shift assays indicate that in isolation, nsp10 binds single- and double-stranded RNA and DNA with high-micromolar affinity and without obvious sequence specificity. It is possible that nsp10 functions within a larger RNA-binding protein complex. However, its exact role within the replicase complex is still not clear.",,"['Joseph, Jeremiah S.', 'Saikatendu, Kumar Singh', 'Subramanian, Vanitha', 'Neuman, Benjamin W.', 'Brooun, Alexei', 'Griffith, Mark', 'Moy, Kin', 'Yadav, Maneesh K.', 'Velasquez, Jeffrey', 'Buchmeier, Michael J.', 'Stevens, Raymond C.', 'Kuhn, Peter']",,,,
,PMC,Molecular Evolution Analysis and Geographic Investigation of Severe Acute Respiratory Syndrome Coronavirus-Like Virus in Palm Civets at an Animal Market and on Farms,http://dx.doi.org/10.1128/JVI.01072-06,PMC1563723,,,,,"['Kan, Biao', 'Wang, Ming', 'Jing, Huaiqi', 'Xu, Huifang', 'Jiang, Xiugao', 'Yan, Meiying', 'Liang, Weili', 'Zheng, Han', 'Wan, Kanglin', 'Liu, Qiyong', 'Cui, Buyun', 'Xu, Yanmei', 'Zhang, Enmin', 'Wang, Hongxia', 'Ye, Jingrong', 'Li, Guichang', 'Li, Machao', 'Cui, Zhigang', 'Qi, Xiaobao', 'Chen, Kai', 'Du, Lin', 'Gao, Kai', 'Zhao, Yu-teng', 'Zou, Xiao-zhong', 'Feng, Yue-Ju', 'Gao, Yu-Fan', 'Hai, Rong', 'Yu, Dongzhen', 'Guan, Yi', 'Xu, Jianguo']",,,,
,PMC,Prevalence and Genetic Diversity of Coronaviruses in Bats from China,http://dx.doi.org/10.1128/JVI.00697-06,PMC1563713,,,"Coronaviruses can infect a variety of animals including poultry, livestock, and humans and are currently classified into three groups. The interspecies transmissions of coronaviruses between different hosts form a complex ecosystem of which little is known. The outbreak of severe acute respiratory syndrome (SARS) and the recent identification of new coronaviruses have highlighted the necessity for further investigation of coronavirus ecology, in particular the role of bats and other wild animals. In this study, we sampled bat populations in 15 provinces of China and reveal that approximately 6.5% of the bats, from diverse species distributed throughout the region, harbor coronaviruses. Full genomes of four coronavirues from bats were sequenced and analyzed. Phylogenetic analyses of the spike, envelope, membrane, and nucleoprotein structural proteins and the two conserved replicase domains, putative RNA-dependent RNA polymerase and RNA helicase, revealed that bat coronaviruses cluster in three different groups: group 1, another group that includes all SARS and SARS-like coronaviruses (putative group 4), and an independent bat coronavirus group (putative group 5). Further genetic analyses showed that different species of bats maintain coronaviruses from different groups and that a single bat species from different geographic locations supports similar coronaviruses. Thus, the findings of this study suggest that bats may play an integral role in the ecology and evolution of coronaviruses.",,"['Tang, X. C.', 'Zhang, J. X.', 'Zhang, S. Y.', 'Wang, P.', 'Fan, X. H.', 'Li, L. F.', 'Li, G.', 'Dong, B. Q.', 'Liu, W.', 'Cheung, C. L.', 'Xu, K. M.', 'Song, W. J.', 'Vijaykrishna, D.', 'Poon, L. L. M.', 'Peiris, J. S. M.', 'Smith, G. J. D.', 'Chen, H.', 'Guan, Y.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus 7a Accessory Protein Is a Viral Structural Protein,http://dx.doi.org/10.1128/JVI.00414-06,PMC1563709,,,"Severe acute respiratory syndrome coronavirus (SCoV) 7a protein is one of the viral accessory proteins. In expressing cells, 7a protein exhibits a variety of biological activities, including induction of apoptosis, activation of the mitogen-activated protein kinase signaling pathway, inhibition of host protein translation, and suppression of cell growth progression. Analysis of SCoV particles that were purified by either sucrose gradient equilibrium centrifugation or a virus capture assay, in which intact SCoV particles were specifically immunoprecipitated by anti-S protein monoclonal antibody, demonstrated that 7a protein was associated with purified SCoV particles. Coexpression of 7a protein with SCoV S, M, N, and E proteins resulted in production of virus-like particles (VLPs) carrying 7a protein, while 7a protein was not released from cells expressing 7a protein alone. Although interaction between 7a protein and another SCoV accessory protein, 3a, has been reported, 3a protein was dispensable for assembly of 7a protein into VLPs. S protein was not required for the 7a protein incorporation into VLPs, and yet 7a protein interacted with S protein in coexpressing cells. These data established that, in addition to 3a protein, 7a protein was a SCoV accessory protein identified as a SCoV structural protein.",,"['Huang, Cheng', 'Ito, Naoto', 'Tseng, Chien-Te K.', 'Makino, Shinji']",,,,
,PMC,What's in this issue?,http://dx.doi.org/10.1016/j.pcrj.2006.05.002,PMC6730814,,,,,"Levy, Mark L.",,,,
,PMC,Avian Influenza: preparation not panic,http://dx.doi.org/10.1016/j.pcrj.2006.05.001,PMC6730813,,,,,"Richards, Guy",,,,
,PMC,The pandemic influenza threat: a review from the primary care perspective,http://dx.doi.org/10.1016/j.pcrj.2006.04.193,PMC6730812,,,"AIMS: This paper aims to summarise the growing literature concerning an imminent future influenza pandemic, from the primary care perspective. METHODS: Sources of literature were scanned and relevant material short-listed for further study from: (1) WHO and CDC websites; (2) PUBMED; and (3) papers mentioned in references of full-text papers. RESULTS: Outbreaks of avian influenza in Asia and elsewhere indicate that the world may be moving towards a pandemic influenza outbreak. The WHO Global Influenza Preparedness Plan 2005 unifies the world with the vision of tackling the next pandemic influenza outbreak as a global effort that includes healthcare provider and patient alike. CONCLUSIONS: We need to update ourselves and keep our staff and patients informed to make infection control measures part of our daily activities. In areas where there are contacts with animal reservoirs of influenza A, patients need to be reminded that they need to protect themselves from being infected.",,"['Goh, Lee Gan', 'Cheong, Pak Yean']",,,,
,PMC,Crystal structure and mechanistic determinants of SARS coronavirus nonstructural protein 15 define an endoribonuclease family,http://dx.doi.org/10.1073/pnas.0601708103,PMC2131687,,,"The ≈30-kb coronavirus (+)RNA genome is replicated and transcribed by a membrane-bound replicase complex made up of 16 viral nonstructural proteins (nsp) with multiple enzymatic activities. The complex includes an RNA endonuclease, NendoU, that is conserved among nidoviruses but no other RNA virus, making it a genetic marker of this virus order. NendoU (nsp15) is a Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2′–3′-cyclic phosphates 5′ to the cleaved bond. Neither biochemical nor sequence homology criteria allow a classification of nsp15 into existing endonuclease families. Here, we report the crystal structure of the severe acute respiratory syndrome coronavirus nsp15 at 2.6-Å resolution. Nsp15 exhibits a unique fold and assembles into a toric hexamer with six potentially active, peripheric catalytic sites. The structure and the spatial arrangement of the catalytic residues into an RNase A-like active site define a separate endonuclease family, endoU, and represent another spectacular example of convergent evolution toward an enzymatic function that is critically involved in the coronavirus replication cycle.",,"['Ricagno, Stefano', 'Egloff, Marie-Pierre', 'Ulferts, Rachel', 'Coutard, Bruno', 'Nurizzo, Didier', 'Campanacci, Valérie', 'Cambillau, Christian', 'Ziebuhr, John', 'Canard, Bruno']",,,,
,PMC,Histidine Triad-Like Motif of the Rotavirus NSP2 Octamer Mediates Both RTPase and NTPase Activities,http://dx.doi.org/10.1016/j.jmb.2006.07.050,PMC1924841,,,"Rotavirus NSP2 is an abundant nonstructural RNA-binding protein essential for forming the viral factories that support replication of the double-stranded RNA genome. NSP2 exists as stable doughnut-shaped octamers within the infected cell, representing the tail-to-tail interaction of two tetramers. Extending diagonally across the surface of each octamer are four highly basic grooves that function as binding sites for single-stranded RNA. Between the N and C-terminal domains of each monomer is a deep electropositive cleft containing a catalytic site that hydrolyzes the γ-β phosphoanhydride bond of any NTP. The catalytic site has similarity to those of the histidine triad (HIT) family of nucleotide-binding proteins. Due to the close proximity of the grooves and clefts, we investigated the possibility that the RNA-binding activity of the groove promoted the insertion of the 5′-triphosphate moiety of the RNA into the cleft, and the subsequent hydrolysis of its γ-β phosphoanhydride bond. Our results show that NSP2 hydrolyzes the γP from RNAs and NTPs through Mg(2+)-dependent activities that proceed with similar reaction velocities, that require the catalytic His(225) residue, and that produce a phosphorylated intermediate. Competition assays indicate that although both substrates enter the active site, RNA is the preferred substrate due to its higher affinity for the octamer. The RTPase activity of NSP2 may account for the absence of 5′-terminal γP on the (−) strands of the dsRNA genome segments. This is the first report of a HIT-like protein with a multifunctional catalytic site, capable of accommodating both NTPs and RNAs during γP hydrolysis.",,"['Carpio, Rodrigo Vasquez-Del', 'Gonzalez-Nilo, Fernando D.', 'Riadi, Gonzalo', 'Taraporewala, Zenobia F.', 'Patton., John T.']",,,,
,PMC,SARS transmission in Vietnam outside of the health-care setting,http://dx.doi.org/10.1017/S0950268806006996,PMC2870589,,,"To evaluate the risk of transmission of SARS coronavirus outside of the health-care setting, close household and community contacts of laboratory-confirmed SARS cases were identified and followed up for clinical and laboratory evidence of SARS infection. Individual- and household-level risk factors for transmission were investigated. Nine persons with serological evidence of SARS infection were identified amongst 212 close contacts of 45 laboratory- confirmed SARS cases (secondary attack rate 4·2%, 95% CI 1·5–7). In this cohort, the average number of secondary infections caused by a single infectious case was 0·2. Two community contacts with laboratory evidence of SARS coronavirus infection had mild or sub-clinical infection, representing 3% (2/65) of Vietnamese SARS cases. There was no evidence of transmission of infection before symptom onset. Physically caring for a symptomatic laboratory-confirmed SARS case was the only independent risk factor for SARS transmission (OR 5·78, 95% CI 1·23–24·24).",,"['TUAN, P.\xa0A.', 'HORBY, P.', 'DINH, P.\xa0N.', 'MAI, L.\xa0T.\xa0Q.', 'ZAMBON, M.', 'SHAH, J.', 'HUY, V.\xa0Q.', 'BLOOM, S.', 'GOPAL, R.', 'COMER, J.', 'PLANT, A.', None]",,,,
,PMC,Contact tracing strategies in heterogeneous populations,http://dx.doi.org/10.1017/S0950268806006923,PMC2870583,,,"Contact tracing is a well-established disease control measure that seeks to uncover cases by following chains of infection. This paper examines mathematical models of both single-step and iterative contact tracing schemes and analyses the ability of these procedures to trace core groups and the sensitivity of the intervention to the timescale of tracing. An iterative tracing process is shown to be particularly effective at uncovering high-risk individuals, and thus it provides a powerful public health tool. Further targeting of tracing effort is considered. When the population exhibits like-with-like (assortative) mixing the required effort for eradication can be significantly reduced by preferentially tracing the contacts of high-risk individuals; in populations where individuals have reliable information about their contacts, further gains in efficiency can be realized. Contact tracing is, therefore, potentially an even more potent tool than its present usage suggests.",,"Eames, K. T. D.",,,,
,PMC,Utilization of host SR protein kinases and RNA-splicing machinery during viral replication,http://dx.doi.org/10.1073/pnas.0604616103,PMC1544086,,,"Although the viral genome is often quite small, it encodes a broad series of proteins. The virus takes advantage of the host-RNA-processing machinery to provide the alternative splicing capability necessary for the expression of this proteomic diversity. Serine–arginine-rich (SR) proteins and the kinases that activate them are central to this alternative splicing machinery. In studies reported here, we use the HIV genome as a model. We show that HIV expression decreases overall SR protein/activity. However, we also show that HIV expression is significantly increased (20-fold) when one of the SR proteins, SRp75 is phosphorylated by SR protein kinase (SRPK)2. Thus, inhibitors of SRPK2 and perhaps of functionally related kinases, such as SRPK1, could be useful antiviral agents. Here, we develop this hypothesis and show that HIV expression down-regulates SR proteins in Flp-In293 cells, resulting in only low-level HIV expression in these cells. However, increasing SRPK2 function up-regulates HIV expression. In addition, we introduce SR protein phosphorylation inhibitor 340 (SRPIN340), which preferentially inhibits SRPK1 and SRPK2 and down-regulates SRp75. Although an isonicotinamide compound, SPRIN340 (or its derivatives) remain to be optimized for better specificity and lower cytotoxicity, we show here that SRPIN340 suppresses propagation of Sindbis virus in plaque assay and variably suppresses HIV production. Thus, we show that SRPK, a well known kinase in the cellular RNA-processing machinery, is used by at least some viruses for propagation and hence suggest that SRPIN340 or its derivatives may be useful for curbing viral diseases.",,"['Fukuhara, Takeshi', 'Hosoya, Takamitsu', 'Shimizu, Saki', 'Sumi, Kengo', 'Oshiro, Takako', 'Yoshinaka, Yoshiyuki', 'Suzuki, Masaaki', 'Yamamoto, Naoki', 'Herzenberg, Leonore A.', 'Herzenberg, Leonard A.', 'Hagiwara, Masatoshi']",,,,
,PMC,Acute exacerbations,,PMC1489228,,,,,"['Currie, Graeme P', 'Wedzicha, Jadwiga A']",,,,
,PMC,Current issues in endoscope reprocessing and infection control during gastrointestinal endoscopy,http://dx.doi.org/10.3748/wjg.v12.i25.3953,PMC4087702,,,"The purpose of this article is to review the evidence regarding transmission of infection during gastrointestinal endoscopy, factors important in endoscope reprocessing and infection control, areas to focus on to improve compliance, and recent developments and advances in the field.",,"['Nelson, Douglas B', 'Muscarella, Lawrence F']",,,,
,PMC,Rabies Virus Glycoprotein as a Carrier for Anthrax Protective Antigen,http://dx.doi.org/10.1016/j.virol.2006.05.010,PMC1576297,,,"Live viral vectors expressing foreign antigens have shown great promise as vaccines against viral diseases. However, safety concerns remain a major problem regarding the use of even highly attenuated viral vectors. Using the rabies virus (RV) envelope protein as a carrier molecule we show here that inactivated RV particles can be utilized to present Bacillus anthracis protective antigen (PA) domain-4 in the viral membrane. In addition to the RV glycoprotein (G) transmembrane and cytoplasmic domains, a portion of the RV G ectodomain was required to express the chimeric RV G anthrax PA on the cell surface. The novel antigen was also efficiently incorporated into RV virions. Mice immunized with the inactivated recombinant RV virions exhibited seroconversion against both RV G and anthrax PA, and a second inoculation greatly increased these responses. These data demonstrate that a viral envelope protein can carry a bacterial protein and that a viral carrier can display whole polypeptides compared to the limited epitope presentation of previous viral systems.",,"['Smith, Mary Ellen', 'Koser, Martin', 'Xiao, Sa', 'Siler, Catherine', 'McGettigan, James P.', 'Calkins, Catherine', 'Pomerantz, Roger J.', 'Dietzschold, Bernhard', 'Schnell, Matthias J.']",,,,
,PMC,Expression of DC-SIGN and DC-SIGNR on Human Sinusoidal Endothelium : A Role for Capturing Hepatitis C Virus Particles,http://dx.doi.org/10.2353/ajpath.2006.051191,PMC1698775,,,"Hepatic sinusoidal endothelial cells are unique among endothelial cells in their ability to internalize and process a diverse range of antigens. DC-SIGNR, a type 2 C-type lectin expressed on liver sinusoids, has been shown to bind with high affinity to hepatitis C virus (HCV) E2 glycoprotein. DC-SIGN is a closely related homologue reported to be expressed only on dendritic cells and a subset of macrophages and has similar binding affinity to HCV E2 glycoprotein. These receptors function as adhesion and antigen presentation molecules. We report distinct patterns of DC-SIGNR and DC-SIGN expression in human liver tissue and show for the first time that both C-type lectins are expressed on sinusoidal endothelial cells. We confirmed that these receptors are functional by demonstrating their ability to bind HCV E2 glycoproteins. Although these lectins on primary sinusoidal cells support HCV E2 binding, they are unable to support HCV entry. These data support a model where DC-SIGN and DC-SIGNR on sinusoidal endothelium provide a mechanism for high affinity binding of circulating HCV within the liver sinusoids allowing subsequent transfer of the virus to underlying hepatocytes, in a manner analogous to DC-SIGN presentation of human immunodeficiency virus on dendritic cells.",,"['Lai, Wai K.', 'Sun, Phoebe J.', 'Zhang, Jie', 'Jennings, Adam', 'Lalor, Patricia F.', 'Hubscher, Stefan', 'McKeating, Jane A.', 'Adams, David H.']",,,,
,PMC,Pathogenic Role for Virus-Specific CD4 T Cells in Mice with Coronavirus-Induced Acute Encephalitis,http://dx.doi.org/10.2353/ajpath.2006.051308,PMC1698761,,,"Acute viral encephalitis is believed to result from direct virus destruction of infected cells and from virus-induced host immune response, but the relative contribution of each remains largely unknown. For example, C57BL/6 (B6) mice infected with mouse hepatitis virus (JHM strain, JHMV) develop severe encephalitis, with death occurring within 7 days. Here, we show that the host response to a single JHMV-specific immunodominant CD4 T-cell epitope is critical for severe disease. We engineered a recombinant JHMV with mutations in the immunodominant CD4 T-cell epitope (rJ.M(Y135Q)). Infection of naïve B6 mice with this virus resulted in mild disease with no mortality. However, introduction of a CD4 T-cell epitope from Listeria monocytogenes into rJ.M(Y135Q) generated a highly virulent virus. The decrease in disease severity was not due to a switch from Th1 to Th2 predominance in rJ.M(Y135Q)-infected mice, an effect on CD8 T-cell function, or differential expression of tumor necrosis factor-α by JHMV-specific CD4 T cells. These results show that the response to a single virus-specific CD4 T-cell epitope may contribute to a pathogenic host response in the setting of acute viral disease and that abrogation of this response ameliorates clinical disease without diminishing virus clearance.",,"['Anghelina, Daniela', 'Pewe, Lecia', 'Perlman, Stanley']",,,,
,PMC,"Chinese man died three years ago of avian flu, not SARS",,PMC1488738,,,,,"Parry, Jane",,,,
,PMC,Q fever endocarditis: A case report and review of the literature,,PMC2560519,,,"The case of a 31-year-old man from Alberta diagnosed with Q fever endocarditis is presented. To the authors’ knowledge, this is the first case of Q fever endocarditis diagnosed in the province of Alberta. The patient had undergone open valvulotomy for congenital aortic stenosis as an infant. He presented with congestive heart failure secondary to severe aortic regurgitation and underwent mechanical aortic valve replacement. Early failure of the mechanical prosthesis and numerous laboratory abnormalities prompted an investigation for endocarditis, which was initially negative. Markedly positive serology eventually established the diagnosis of chronic Q fever. The patient subsequently underwent a second aortic valve replacement following initiation of appropriate antimicrobials directed against Coxiella burnetii. The present report reviews the clinical presentation and diagnosis of Q fever endocarditis. It highlights the insidious and nonspecific nature of the presenting symptoms, and emphasizes the use of serology for diagnosis. Increased awareness and earlier diagnosis can significantly decrease the morbidity and mortality associated with this disease.",,"['Deyell, Marc W', 'Chiu, Brian', 'Ross, David B', 'Alvarez, Nanette']",,,,
,PMC,Infectious Disease Management: Lessons from Cuba,,PMC2095081,,,,,"['MacDonald, Noni E', 'Halperin, Beth', 'Chaple, Enrique Beldarrain', 'Scott, Jeff', 'Kirk, John M']",,,,
,PMC,Planning for the Pandemic,,PMC2095078,,,,,"Embree, Joanne",,,,
,PMC,Infection with Porcine reproductive and respiratory syndrome virus stimulates an early gamma interferon response in the serum of pigs,,PMC1477926,,,"The early release of cytokines by cells involved in innate immunity is an important host response to intracellular pathogens. Gamma interferon (IFN-γ) is an important cytokine produced during the early stages of an infection by macrophages, natural killer (NK) cells, and other cell types, and it is also a central cytokine mediator for the induction of cellular or Th1 immunity. To better understand innate and adaptive immune responses after infection with Porcine reproductive and respiratory syndrome virus (PRRSV), we investigated serum IFN-γ concentrations and the duration of viremia. For 2 strains of atypical PRRSV, IFN-γ was detectable in swine serum soon after infection and lasted for approximately 3 wk. Serum concentrations of IFN-γ peaked at about 10 d after inoculation and returned to approximately baseline levels by day 22. However, individual pigs manifested short, sporadic increases in the serum concentration of IFN-γ from 18 to 50 d after inoculation. Prior vaccination blocked the serum IFN-γ response associated with homologous virus challenge and altered the kinetics of the response after heterologous challenge. Two other respiratory viruses of pigs, Porcine respiratory coronavirus and Swine influenza virus, do not appear to induce serum IFN-γ. The early production of IFN-γ in PRRSV-infected pigs might result from activation of NK cells, a response that is more characteristic of immune pathways stimulated by intracellular bacterial and protozoan infections.",,"['Wesley, Ronald D.', 'Lager, Kelly M.', 'Kehrli, Marcus E.']",,,,
,PMC,Progressive dyspnea associated with a crazy-paving appearance on a chest computed tomography scan,,PMC2683306,,,"A ‘crazy-paving’ appearance of the lungs on computed tomography scanning of the chest was first described nearly 20 years ago in patients with pulmonary alveolar proteinosis, and was thought to be characteristic of this condition. However, this pattern has subsequently been reported in a variety of pulmonary diseases and is now considered to be nonspecific. The present report describes a case of a 74-year-old man in whom congestive heart failure presented with a crazy-paving appearance of the lungs on a chest computed tomography scan. This uncommon association illustrates the importance of the correlation of clinical and radiographic information.",,"['Maimon, Nimrod', 'Paul, Narinder', 'Downey, Gregory P']",,,,
,PMC,Bats: Important Reservoir Hosts of Emerging Viruses,http://dx.doi.org/10.1128/CMR.00017-06,PMC1539106,,,"Bats (order Chiroptera, suborders Megachiroptera [“flying foxes”] and Microchiroptera) are abundant, diverse, and geographically widespread. These mammals provide us with resources, but their importance is minimized and many of their populations and species are at risk, even threatened or endangered. Some of their characteristics (food choices, colonial or solitary nature, population structure, ability to fly, seasonal migration and daily movement patterns, torpor and hibernation, life span, roosting behaviors, ability to echolocate, virus susceptibility) make them exquisitely suitable hosts of viruses and other disease agents. Bats of certain species are well recognized as being capable of transmitting rabies virus, but recent observations of outbreaks and epidemics of newly recognized human and livestock diseases caused by viruses transmitted by various megachiropteran and microchiropteran bats have drawn attention anew to these remarkable mammals. This paper summarizes information regarding chiropteran characteristics and information regarding 66 viruses that have been isolated from bats. From these summaries, it is clear that we do not know enough about bat biology; we are doing too little in terms of bat conservation; and there remain a multitude of questions regarding the role of bats in disease emergence.",,"['Calisher, Charles H.', 'Childs, James E.', 'Field, Hume E.', 'Holmes, Kathryn V.', 'Schountz, Tony']",,,,
,PMC,Epidemiology of Human Metapneumovirus,http://dx.doi.org/10.1128/CMR.00014-06,PMC1539100,,,"Since the discovery of human metapneumovirus (hMPV) in 2001, the virus has been identified worldwide. hMPV is a common respiratory pathogen, particularly in infants and young children. The virus is associated with both upper and lower respiratory tract infections and may be a trigger for asthma. At least two major genotypes of hMPV circulate during community outbreaks. Whether these genotypes represent distinct serotypes remains controversial. The major challenges faced by the medical and scientific communities are the understanding of the pathogenesis of hMPV disease and the development of a safe and effective vaccine to protect against infection and disease caused by this newly recognized respiratory virus.",,"Kahn, Jeffrey S.",,,,
,PMC,Chemical microarray: a new tool for drug screening and discovery,http://dx.doi.org/10.1016/j.drudis.2006.05.002,PMC2577215,,,"HTS with microtiter plates has been the major tool used in the pharmaceutical industry to explore chemical diversity space and to identify active compounds and pharmacophores for specific biological targets. However, HTS faces a daunting challenge regarding the fast-growing numbers of drug targets arising from genomic and proteomic research, and large chemical libraries generated from high-throughput synthesis. There is an urgent need to find new ways to profile the activity of large numbers of chemicals against hundreds of biological targets in a fast, low-cost fashion. Chemical microarray can rise to this challenge because it has the capability of identifying and evaluating small molecules as potential therapeutic reagents. During the past few years, chemical microarray technology, with different surface chemistries and activation strategies, has generated many successes in the evaluation of chemical–protein interactions, enzyme activity inhibition, target identification, signal pathway elucidation and cell-based functional analysis. The success of chemical microarray technology will provide unprecedented possibilities and capabilities for parallel functional analysis of tremendous amounts of chemical compounds.",,"['Ma, Haiching', 'Horiuchi, Kurumi Y.']",,,,
,PMC,Comparison of Real-Time PCR Assays with Fluorescent-Antibody Assays for Diagnosis of Respiratory Virus Infections in Children,http://dx.doi.org/10.1128/JCM.00216-06,PMC1489473,,,"Conventional fluorescent-antibody (FA) methods were compared to real-time PCR assays for detection of respiratory syncytial virus (RSV), influenza virus type A (FluA), parainfluenza virus types 1, 2, and 3 (PIV1, PIV2, and PIV3), human metapneumovirus (MPV), and adenovirus (AdV) in 1,138 specimens from children with respiratory illnesses collected over a 1-year period. At least one virus was detected in 436 (38.3%) specimens by FA and in 608 (53.4%) specimens by PCR (P < 0.001). Specimen quality was inadequate for FA in 52 (4.6%) specimens; 13 of these (25%) were positive by PCR. In contrast, 18 (1.6%) specimens could not be analyzed by PCR; 1 of these was positive by FA. The number of specimens positive only by PCR among specimens positive by PCR and/or FA was 18 (7.0%) of 257 for RSV, 18 (13.4%) of 134 for FluA, 25 (64.1%) of 39 for PIV1, 8 (88.9%) of 9 for PIV2, 17 (30.1%) of 55 for PIV3, and 101 (76.5%) of 132 for AdV. MPV was detected in 6.6% of all specimens and in 9.5% of the 702 specimens negative by FA. The mean number of virus copies per milliliter in specimens positive by both PCR and FA was significantly higher, at 6.7 × 10(7), than that in specimens positive only by PCR, at 4.1 × 10(4) (P < 0.001). The PCR assays were significantly more sensitive than FA assays for detecting respiratory viruses, especially parainfluenza virus and adenovirus. Use of real-time PCR to identify viral respiratory pathogens in children will lead to improved diagnosis of respiratory illness.",,"['Kuypers, Jane', 'Wright, Nancy', 'Ferrenberg, James', 'Huang, Meei-Li', 'Cent, Anne', 'Corey, Lawrence', 'Morrow, Rhoda']",,,,
,PMC,Survey of Dogs in Japan for Group 2 Canine Coronavirus Infection,http://dx.doi.org/10.1128/JCM.02397-05,PMC1489469,,,Specimens obtained from 96 dogs with respiratory and enteric clinical signs in Japan were retrospectively examined for group 2 coronavirus by reverse transcription-PCR. Two dogs were found to be positive. Phylogenetic analysis of the spike gene indicated that they were most probably related to the canine respiratory coronavirus recently described in the United Kingdom.,,"['Yachi, Akiko', 'Mochizuki, Masami']",,,,
,PMC,Transmission potential of primary pneumonic plague: time inhomogeneous evaluation based on historical documents of the transmission network,http://dx.doi.org/10.1136/jech.2005.042424,PMC2566243,,,"BACKGROUND: The transmission potential of primary pneumonic plague, caused by Yersinia pestis, is one of the key epidemiological determinants of a potential biological weapon, and requires clarification and time dependent interpretation. METHOD: This study estimated the reproduction number and its time dependent change through investigations of outbreaks in Mukden, China (1946), and Madagascar (1957). Reconstruction of an epidemic tree, which shows who infected whom, from the observed dates of onset was performed using the serial interval. Furthermore, a likelihood based approach was used for the time inhomogeneous evaluation of the outbreaks for which there was scarcity of cases. RESULTS: According to the estimates, the basic reproduction number, R(0), was on the order of 2.8 to 3.5, which is higher than previous estimates. The lower 95% confidence intervals of R(0) exceeded unity. The effective reproduction number declined below unity after control measures were introduced in Mukden, and before the official implementation in Madagascar. CONCLUSION: While the time course of the latter outbreak could be explained by intrinsic factors and stochasticity in this remote and scarcely populated area, the former in Mukden suggests the possible continued chains of transmission in highly populated areas. Using the proposed methods, the who infected whom information permitted the evaluation of the time inhomogeneous transmission potential in relation to public health measures. The study also tackles the problem of statistical estimation of R(0) based on similar information, which was previously performed simply by counting the number of secondary transmissions regardless of time.",,"['Nishiura, Hiroshi', 'Schwehm, Markus', 'Kakehashi, Masayuki', 'Eichner, Martin']",,,,
,PMC,The University of Washington Health Sciences Library BioCommons: an evolving Northwest biomedical research information support infrastructure,,PMC1525310,,,"Setting: The University of Washington Health Sciences Libraries and Information Center BioCommons serves the bioinformatics needs of researchers at the university and in the vibrant for-profit and not-for-profit biomedical research sector in the Washington area and region. Program Components: The BioCommons comprises services addressing internal University of Washington, not-for-profit, for-profit, and regional and global clientele. The BioCommons is maintained and administered by the BioResearcher Liaison Team. The BioCommons architecture provides a highly flexible structure for adapting to rapidly changing resources and needs. Evaluation Mechanisms: BioCommons uses Web-based pre- and post-course evaluations and periodic user surveys to assess service effectiveness. Recent surveys indicate substantial usage of BioCommons services and a high level of effectiveness and user satisfaction. Next Steps/Future Directions: BioCommons is developing novel collaborative Web resources to distribute bioinformatics tools and is experimenting with Web-based competency training in bioinformation resource use.",,"['Minie, Mark', 'Bowers, Stuart', 'Tarczy-Hornoch, Peter', 'Roberts, Edward', 'James, Rose A.', 'Rambo, Neil', 'Fuller, Sherrilynne']",,,,
,PMC,"Evolutionary History of the Closely Related Group 2 Coronaviruses: Porcine Hemagglutinating Encephalomyelitis Virus, Bovine Coronavirus, and Human Coronavirus OC43",http://dx.doi.org/10.1128/JVI.02675-05,PMC1489060,,,"The close genetic and antigenic relatedness among the group 2 coronaviruses human coronavirus OC43 (HCoV-OC43), bovine coronavirus (BCoV), and porcine hemagglutinating encephalomyelitis virus (PHEV) suggests that these three viruses with different host specificities diverged fairly recently. In this study, we determined the complete genomic sequence of PHEV (strain PHEV-VW572), revealing the presence of a truncated group 2-specific ns2 gene in PHEV in comparison to other group 2 coronaviruses. Using a relaxed molecular clock approach, we reconstructed the evolutionary relationships between PHEV, BCoV, and HCoV-OC43 in real-time units, which indicated relatively recent common ancestors for these species-specific coronaviruses.",,"['Vijgen, Leen', 'Keyaerts, Els', 'Lemey, Philippe', 'Maes, Piet', 'Van Reeth, Kristien', 'Nauwynck, Hans', 'Pensaert, Maurice', 'Van Ranst, Marc']",,,,
,PMC,Both Spike and Background Genes Contribute to Murine Coronavirus Neurovirulence,http://dx.doi.org/10.1128/JVI.00432-06,PMC1489045,,,"Various strains of mouse hepatitis virus (MHV) exhibit different pathogenic phenotypes. Infection with the A59 strain of MHV induces both encephalitis and hepatitis, while the highly neurovirulent JHM strain induces a fatal encephalitis with little, if any, hepatitis. The pathogenic phenotype for each strain is determined by the genetic composition of the viral genome, as well as the host immune response. Using isogenic recombinant viruses with A59 background genes differing only in the spike gene, we have previously shown that high neurovirulence is associated with the JHM spike protein, the protein responsible for attachment to the host cell receptor (J. J. Phillips, M. M. Chua, G. F. Rall, and S. R. Weiss, Virology 301:109-120, 2002). Using another set of isogenic recombinant viruses with JHM background genes expressing either the JHM or A59 spike, we have further investigated the roles of viral genes in pathogenesis. Here, we demonstrate that the high neurovirulence of JHM is associated with accelerated spread through the brain and a heightened innate immune response that is characterized by high numbers of infiltrating neutrophils and macrophages, suggesting an immunopathogenic component to neurovirulence. While expression of the JHM spike is sufficient to confer a neurovirulent phenotype, as well as increased macrophage infiltration, background genes contribute to virulence as well, at least in part, by dictating the extent of the T-cell immune response.",,"['Iacono, Kathryn T.', 'Kazi, Lubna', 'Weiss, Susan R.']",,,,
,PMC,CD1d Mediates T-Cell-Dependent Resistance to Secondary Infection with Encephalomyocarditis Virus (EMCV) In Vitro and Immune Response to EMCV Infection In Vivo,http://dx.doi.org/10.1128/JVI.02745-05,PMC1489038,,,"The innate and adaptive immune responses have evolved distinct strategies for controlling different viral pathogens. Encephalomyocarditis virus (EMCV) is a picornavirus that can cause paralysis, diabetes, and myocarditis within days of infection. The optimal innate immune response against EMCV in vivo requires CD1d. Interaction of antigen-presenting cell CD1d with distinct natural killer T-cell (“NKT”) populations can induce rapid gamma interferon (IFN-γ) production and NK-cell activation. The T-cell response of CD1d-deficient mice (lacking all NKT cells) against acute EMCV infection was further studied in vitro and in vivo. EMCV persisted at higher levels in CD1d-knockout (KO) splenocyte cultures infected in vitro. Furthermore, optimal resistance to repeat cycles of EMCV infection in vitro was also shown to depend on CD1d. However, this was not reflected in the relative levels of NK-cell activation but rather by the responses of both CD4(+) and CD8(+) T-cell populations. Repeated EMCV infection in vitro induced less IFN-γ and alpha interferon (IFN-α) from CD1d-deficient splenocytes than with the wild type. Furthermore, the level of EMCV replication in wild-type splenocytes was markedly and specifically increased by addition of blocking anti-CD1d antibody. Depletion experiments demonstrated that dendritic cells contributed less than the combination of NK and NKT cells to anti-EMCV responses and that none of these cell types was the main source of IFN-α. Finally, EMCV infection in vivo produced higher levels of viremia in CD1d-KO mice than in wild-type animals, coupled with significantly less lymphocyte activation and IFN-α production. These results point to the existence of a previously unrecognized mechanism of rapid CD1d-dependent stimulation of the antiviral adaptive cellular immune response.",,"['Ilyinskii, Petr O.', 'Wang, Ruojie', 'Balk, Steven P.', 'Exley, Mark A.']",,,,
,PMC,Conformational States of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Ectodomain,http://dx.doi.org/10.1128/JVI.02744-05,PMC1489032,,,"The severe acute respiratory syndrome coronavirus enters cells through the activities of a spike protein (S) which has receptor-binding (S1) and membrane fusion (S2) regions. We have characterized four sequential states of a purified recombinant S ectodomain (S-e) comprising S1 and the ectodomain of S2. They are S-e monomers, uncleaved S-e trimers, cleaved S-e trimers, and dissociated S1 monomers and S2 trimer rosettes. Lowered pH induces an irreversible transition from flexible, L-shaped S-e monomers to clove-shaped trimers. Protease cleavage of the trimer occurs at the S1-S2 boundary; an ensuing S1 dissociation leads to a major rearrangement of the trimeric S2 and to formation of rosettes likely to represent clusters of elongated, postfusion trimers of S2 associated through their fusion peptides. The states and transitions of S suggest conformational changes that mediate viral entry into cells.",,"['Li, Fang', 'Berardi, Marcelo', 'Li, Wenhui', 'Farzan, Michael', 'Dormitzer, Philip R.', 'Harrison, Stephen C.']",,,,
,PMC,Comparative Analysis of 22 Coronavirus HKU1 Genomes Reveals a Novel Genotype and Evidence of Natural Recombination in Coronavirus HKU1,http://dx.doi.org/10.1128/JVI.00509-06,PMC1489027,,,"We sequenced and compared the complete genomes of 22 strains of coronavirus HKU1 (CoV HKU1) obtained from nasopharyngeal aspirates of patients with respiratory tract infections over a 2-year period. Phylogenetic analysis of 24 putative proteins and polypeptides showed that the 22 CoV HKU1 strains fell into three clusters (genotype A, 13 strains; genotype B, 3 strains and genotype C, 6 strains). However, different phylogenetic relationships among the three clusters were observed in different regions of their genomes. From nsp4 to nsp6, the genotype A strains were clustered with the genotype B strains. For nsp7 and nsp8 and from nsp10 to nsp16, the genotype A strains were clustered with the genotype C strains. From hemagglutinin esterase (HE) to nucleocapsid (N), the genotype B strains were clustered closely with the genotype C strains. Bootscan analysis showed possible recombination between genotypes B and C from nucleotide positions 11500 to 13000, corresponding to the nsp6-nsp7 junction, giving rise to genotype A, and between genotypes A and B from nucleotide positions 21500 to 22500, corresponding to the nsp16-HE junction, giving rise to genotype C. Multiple alignments further narrowed the sites of crossover to a 143-bp region between nucleotide positions 11750 and 11892 and a 29-bp region between nucleotide positions 21502 and 21530. Genome analysis also revealed various numbers of tandem copies of a perfect 30-base acidic tandem repeat (ATR) which encodes NDDEDVVTGD and various numbers and sequences of imperfect repeats in the N terminus of nsp3 inside the acidic domain upstream of papain-like protease 1 among the 22 genomes. All 10 CoV HKU1 strains with incomplete imperfect repeats (1.4 and 4.4) belonged to genotype A. The present study represents the first evidence for natural recombination in coronavirus associated with human infection. Analysis of a single gene is not sufficient for the genotyping of CoV HKU1 strains but requires amplification and sequencing of at least two gene loci, one from nsp10 to nsp16 (e.g., pol or helicase) and another from HE to N (e.g., spike or N). Further studies will delineate whether the ATR is useful for the molecular typing of CoV HKU1.",,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Yip, Cyril C. Y.', 'Huang, Yi', 'Tsoi, Hoi-Wah', 'Chan, Kwok-Hung', 'Yuen, Kwok-Yung']",,,,
,PMC,Marburgvirus Genomics and Association with a Large Hemorrhagic Fever Outbreak in Angola,http://dx.doi.org/10.1128/JVI.00069-06,PMC1488971,,,"In March 2005, the Centers for Disease Control and Prevention (CDC) investigated a large hemorrhagic fever (HF) outbreak in Uige Province in northern Angola, West Africa. In total, 15 initial specimens were sent to CDC, Atlanta, Ga., for testing for viruses associated with viral HFs known to be present in West Africa, including ebolavirus. Marburgvirus was also included despite the fact that the origins of all earlier outbreaks were linked directly to East Africa. Surprisingly, marburgvirus was confirmed (12 of 15 specimens) as the cause of the outbreak. The outbreak likely began in October 2004 and ended in July 2005, and it included 252 cases and 227 (90%) fatalities (report from the Ministry of Health, Republic of Angola, 2005), making it the largest Marburg HF outbreak on record. A real-time quantitative reverse transcription-PCR assay utilized and adapted during the outbreak proved to be highly sensitive and sufficiently robust for field use. Partial marburgvirus RNA sequence analysis revealed up to 21% nucleotide divergence among the previously characterized East African strains, with the most distinct being Ravn from Kenya (1987). The Angolan strain was less different (∼7%) from the main group of East African marburgviruses than one might expect given the large geographic separation. To more precisely analyze the virus genetic differences between outbreaks and among viruses within the Angola outbreak itself, a total of 16 complete virus genomes were determined, including those of the virus isolates Ravn (Kenya, 1987) and 05DRC, 07DRC, and 09DRC (Democratic Republic of Congo, 1998) and the reference Angolan virus isolate (Ang1379v). In addition, complete genome sequences were obtained from RNAs extracted from 10 clinical specimens reflecting various stages of the disease and locations within the Angolan outbreak. While the marburgviruses exhibit high overall genetic diversity (up to 22%), only 6.8% nucleotide difference was found between the West African Angolan viruses and the majority of East African viruses, suggesting that the virus reservoir species in these regions are not substantially distinct. Remarkably few nucleotide differences were found among the Angolan clinical specimens (0 to 0.07%), consistent with an outbreak scenario in which a single (or rare) introduction of virus from the reservoir species into the human population was followed by person-to-person transmission with little accumulation of mutations. This is in contrast to the 1998 to 2000 marburgvirus outbreak, where evidence of several virus genetic lineages (with up to 21% divergence) and multiple virus introductions into the human population was found.",,"['Towner, Jonathan S.', 'Khristova, Marina L.', 'Sealy, Tara K.', 'Vincent, Martin J.', 'Erickson, Bobbie R.', 'Bawiec, Darcy A.', 'Hartman, Amy L.', 'Comer, James A.', 'Zaki, Sherif R.', 'Ströher, Ute', 'Gomes da Silva, Filomena', 'del Castillo, Fernando', 'Rollin, Pierre E.', 'Ksiazek, Thomas G.', 'Nichol, Stuart T.']",,,,
,PMC,X-Ray Structures of the N- and C-Terminal Domains of a Coronavirus Nucleocapsid Protein: Implications for Nucleocapsid Formation,http://dx.doi.org/10.1128/JVI.00157-06,PMC1488953,,,"Coronaviruses cause a variety of respiratory and enteric diseases in animals and humans including severe acute respiratory syndrome. In these enveloped viruses, the filamentous nucleocapsid is formed by the association of nucleocapsid (N) protein with single-stranded viral RNA. The N protein is a highly immunogenic phosphoprotein also implicated in viral genome replication and in modulating cell signaling pathways. We describe the structure of the two proteolytically resistant domains of the N protein from infectious bronchitis virus (IBV), a prototype coronavirus. These domains are located at its N- and C-terminal ends (NTD and CTD, respectively). The NTD of the IBV Gray strain at 1.3-Å resolution exhibits a U-shaped structure, with two arms rich in basic residues, providing a module for specific interaction with RNA. The CTD forms a tightly intertwined dimer with an intermolecular four-stranded central β-sheet platform flanked by α helices, indicating that the basic building block for coronavirus nucleocapsid formation is a dimeric assembly of N protein. The variety of quaternary arrangements of the NTD and CTD revealed by the analysis of the different crystal forms delineates possible interfaces that could be used for the formation of a flexible filamentous ribonucleocapsid. The striking similarity between the dimeric structure of CTD and the nucleocapsid-forming domain of a distantly related arterivirus indicates a conserved mechanism of nucleocapsid formation for these two viral families.",,"['Jayaram, Hariharan', 'Fan, Hui', 'Bowman, Brian R.', 'Ooi, Amy', 'Jayaram, Jyothi', 'Collisson, Ellen W.', 'Lescar, Julien', 'Prasad, B. V. Venkataram']",,,,
,PMC,Impact of a Spreading Epidemic on Medical Students,,PMC3349482,,,"The emergence of severe acute respiratory syndrome (SARS) had caused fear and anxiety of unprecedented proportion. To examine the impact of SARS on the medical students in a private medical university, a self-reporting questionnaire study was carried out to assess the factual knowledge, anxiety level and perception of the crisis, among the students. The two-week study (between 12 and 23 May, 2003) was carried out three weeks after the first reported SARS-related death in Malaysia. Ninety-one Phase I (junior) and 113 Phase II (senior) students completed the questionnaires. A large majority of students of Phase I and II were correct in their factual knowledge and were sensible in their perception of the future and the handling of the crisis by government(s). However, phase 1 students expressed significantly greater degree of anxiety compared to Phase II in relation to attendance and personal protection in hospital, and in meeting people coughing in public places. The lesser degree of anxiety expressed by phase II senior students may be due in part, to a more realistic assessment of SARS risk brought about by maturity, time spent in hospital and interaction with clinical lecturers and medical staff.",,"['Loh, Li-Cher', 'Ali, Anita Mohd', 'Ang, Ter-Hoay', 'Chelliah, Ambiga']",,,,
,PMC,The potential role of ribosomal frameshifting in generating aberrant proteins implicated in neurodegenerative diseases,http://dx.doi.org/10.1261/rna.84406,PMC1484430,,,"Aberrant forms of proteins ubiquitin B and β-amyloid precusor protein, UBB(+1) and APP(+1), are implicated in human neurodegenerative diseases. They have their carboxyl-terminal regions derived from an alternative reading frame. Transcription slippage has been invoked to explain the production of these proteins from abnormal mRNA. However, ribosomal frameshifting on wild-type mRNA may account for the great majority of the aberrant protein. Ribosomal frameshifting may also be involved in the progression of triplet expansion diseases such as Huntington's and spinocerebellar ataxias. In a particular spinocerebellar ataxia, SCA3, Toulouse and colleagues recently discovered −1 frameshifting in a transcript containing an expanded CAG-repeat. Antibiotics that affect mammalian ribosomes may have complex effects on frameshifting and disease progression.",,"['Wills, Norma M.', 'Atkins, John F.']",,,,
,PMC,The Influence of a Sense of Time on Human Development,http://dx.doi.org/10.1126/science.1127488,PMC2790864,,,"The subjective sense of future time plays an essential role in human motivation. Gradually, time left becomes a better predictor than chronological age for a range of cognitive, emotional, and motivational variables. Socioemotional selectivity theory maintains that constraints on time horizons shift motivational priorities in such a way that the regulation of emotional states becomes more important than other types of goals. This motivational shift occurs with age but also appears in other contexts (for example, geographical relocations, illnesses, and war) that limit subjective future time.",,"Carstensen, Laura L.",,,,
,PMC,Crystallization and preliminary X-ray characterization of aminopeptidase N from Escherichia coli,http://dx.doi.org/10.1107/S1744309106021567,PMC2242940,,,"A recombinant form of aminopeptidase N (molecular weight 99 kDa) from Escherichia coli was crystallized by the hanging-drop vapour-diffusion method using ammonium sulfate as a precipitating agent. The crystals belong to the hexagonal space group P3(1)21, with unit-cell parameters a = b = 120.5, c = 171.0 Å. The crystals are most likely to contain one molecule in the asymmetric unit, with a V (M) value of 3.62 Å(3) Da(−1). Diffraction data were collected to 2.0 Å resolution using Cu Kα radiation from a rotating-anode X-ray generator.",,"['Onohara, Yuko', 'Nakajima, Yoshitaka', 'Ito, Kiyoshi', 'Xu, Yue', 'Nakashima, Kanako', 'Ito, Takashi', 'Yoshimoto, Tadashi']",,,,
,PMC,A Bayesian dynamic model for influenza surveillance,http://dx.doi.org/10.1002/sim.2566,PMC4128871,,,"The severe acute respiratory syndrome (SARS) epidemic, the growing fear of an influenza pandemic and the recent shortage of flu vaccine highlight the need for surveillance systems able to provide early, quantitative predictions of epidemic events. We use dynamic Bayesian networks to discover the interplay among four data sources that are monitored for influenza surveillance. By integrating these different data sources into a dynamic model, we identify in children and infants presenting to the pediatric emergency department with respiratory syndromes an early indicator of impending influenza morbidity and mortality. Our findings show the importance of modelling the complex dynamics of data collected for influenza surveillance, and suggest that dynamic Bayesian networks could be suitable modelling tools for developing epidemic surveillance systems.",,"['Sebastiani, Paola', 'Mandl, Kenneth D.', 'Szolovits, Peter', 'Kohane, Isaac S.', 'Ramoni, Marco F.']",,,,
,PMC,Inhibition of Replication and Transcription Activator and Latency-Associated Nuclear Antigen of Kaposi’s Sarcoma-Associated Herpesvirus by Morpholino Oligomers,http://dx.doi.org/10.1016/j.antiviral.2006.05.017,PMC2390898,,,"Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with Kaposi’s sarcoma and primary effusion lymphoma (PEL). The KSHV replication and transcription activator (RTA) and latency-associated nuclear antigen (LANA) play key roles in activating KSHV lytic replication and maintaining KSHV latency, respectively. Phosphorodiamidate morpholino oligomers (PMO) are similar to short single-stranded DNA oligomers, but possess a modified backbone that confers highly specific binding and resistance to nucleases. In this study, RTA and LANA mRNA in PEL cells were targeted by antisense peptide-conjugated PMO (P-PMO) in an effort to suppress KSHV replication. Highly efficient P-PMO uptake by PEL cells was observed. Treatment of PEL cells with a RTA P-PMO (RP1) reduced RTA expression in a dose-dependent and sequence-specific manner. There was also a significant decrease in several KSHV early and late gene products, including vIL-6, vIRF-1, and ORF-K8.1A. KSHV viral DNA levels were reduced both in cells and culture supernatants of RP1 P-PMO-treated cells, which indicate that KSHV lytic replication was supressed. Treatment of BCBL-1 cells with P-PMO against LANA resulted in a reduction of LANA expression. Cell viability assays detected no cytotoxicity from P-PMO alone, within the concentration range used for the experiments in this study. These results suggest that RP1 P-PMO can specifically block KSHV replication, and further study is warranted.",,"['Zhang, Yan-Jin', 'Wang, Kai-Yu', 'Stein, David A.', 'Patel, Deendayal', 'Watkins, Rheba', 'Moulton, Hong M.', 'Iversen, Patrick L.', 'Matson, David O.']",,,,
,PMC,Identification of pulmonary Oct-4(+) stem/progenitor cells and demonstration of their susceptibility to SARS coronavirus (SARS-CoV) infection in vitro,http://dx.doi.org/10.1073/pnas.0510232103,PMC1480441,,,"In this study, we report a serum-free culture system for primary neonatal pulmonary cells that can support the growth of octamer-binding transcription factor 4(+) (Oct-4(+)) epithelial colonies with a surrounding mesenchymal stroma. In addition to Oct-4, these cells also express other stem cell markers such as stage-specific embryonic antigen 1 (SSEA-1), stem cell antigen 1 (Sca-1), and Clara cell secretion protein (CCSP) but not c-Kit, CD34, and p63, indicating that they represent a subpopulation of Clara cells that have been implicated as lung stem/progenitor cells in lung injury models. These colony cells can be kept for weeks in primary cultures and undergo terminal differentiation to alveolar type-2- and type-1-like pneumocytes sequentially when removed from the stroma. In addition, we have demonstrated the presence of Oct-4(+) long-term BrdU label-retaining cells at the bronchoalveolar junction of neonatal lung, providing a link between the Oct-4(+) cells in vivo and in vitro and strengthening their identity as putative neonatal lung stem/progenitor cells. Lastly, these Oct-4(+) epithelial colony cells, which also express angiotensin-converting enzyme 2, are the target cells for severe acute respiratory syndrome coronavirus infection in primary cultures and support active virus replication leading to their own destruction. These observations imply the possible involvement of lung stem/progenitor cells, in addition to pneumocytes, in severe acute respiratory syndrome coronavirus infection, accounting for the continued deterioration of lung tissues and apparent loss of capacity for lung repair.",,"['Ling, Thai-Yen', 'Kuo, Ming-Der', 'Li, Chung-Leung', 'Yu, Alice L.', 'Huang, Yen-Hua', 'Wu, Tsai-Jung', 'Lin, You-Chin', 'Chen, Shu-Hwa', 'Yu, John']",,,,
,PMC,Study of Automatic Enhancement for Chest Radiograph,http://dx.doi.org/10.1007/s10278-006-0623-7,PMC3045154,,,"Because of the large difference of the densities in the lung and other structures, the chest x-ray image behaves as a wide-range intensity distribution, which brings on a bit of difficulty to investigate the focus. In the paper, according to the intensity properties of the chest radiograph, the chest radiographic image is divided into three subregions, and a piecewise linear transformation model is established. An approach of automatic enhancement is presented, based on the gray-level normalization. The average enhanced ratios of three subregions of the normal and severe acute respiratory syndrome image are increased by 10.70% and 25.55%, respectively. The technique is proved to be effective through the evaluation of the improved images.",,"['Shuyue, Chen', 'Honghua, Hou', 'Yanjun, Zeng', 'Xiaomin, Xu']",,,,
,PMC,Dimerisation-dependent GTPase reaction of MnmE: how potassium acts as GTPase-activating element,http://dx.doi.org/10.1038/sj.emboj.7601171,PMC1500855,,,"MnmE, a Guanine nucleotide-binding protein conserved between bacteria and man, is involved in the modification of tRNAs. Here we provide biochemical and X-ray structural evidence for a new GTP-hydrolysis mechanism, where the G-domains of MnmE dimerise in a potassium-dependent manner and induce GTP hydrolysis. The structure in the presence of GDP-AlF(x) and potassium shows how juxtaposition of the subunits induces a conformational change around the nucleotide which reorients the catalytic machinery. A critical glutamate is positioned such as to stabilise or activate the attacking water. Potassium provides a positive charge into the catalytic site in a position analogous to the arginine finger in the Ras-RasGAP system. Mutational studies show that potassium-dependent dimerisation and GTP hydrolysis can be uncoupled and that interaction between the G-domains is a prerequisite for subsequent phosphoryl transfer. We propose a model for the juxtaposition of G-domains in the full-length protein and how it induces conformational changes in the putative tRNA-modification centre.",,"['Scrima, Andrea', 'Wittinghofer, Alfred']",,,,
,PMC,"Peptides derived from HIV-1, HIV-2, Ebola virus, SARS coronavirus and coronavirus 229E exhibit high affinity binding to the formyl peptide receptor",http://dx.doi.org/10.1016/j.bbadis.2006.05.008,PMC2075610,,,"Peptides derived from the membrane proximal region of fusion proteins of human immunodeficiency viruses 1 and 2, Coronavirus 229 E, severe acute respiratory syndrome coronavirus and Ebola virus were all potent antagonists of the formyl peptide receptor expressed in Chinese hamster ovary cells. Binding of viral peptides was affected by the naturally occurring polymorphisms at residues 190 and 192, which are located at second extracellular loop-transmembrane helix 5 interface. Substitution of R190 with W190 enhanced the affinity for a severe acute respiratory syndrome coronavirus peptide 6 fold but reduced the affinity for N-formyl-Nle–Leu-Phe by 2.5 fold. A 12 mer peptide derived from coronavirus 229E (ETYIKPWWVWL) was the most potent antagonist of the formyl peptide receptor W190 with a K(i) of 230 nM. Fluorescently labeled ETYIKPWWVWL was effectively internalized by all three variants with EC(50) of ~25 nM. An HKU-1 coronavirus peptide, MYVKWPWYVWL, was a potent antagonist but N-formyl-MYVKWPWYVWL was a potent agonist. ETYIKPWWVWL did not stimulate GTPγS binding but inhibited the stimulation by formyl-NleLeuPhe. It also blocked β arrestin translocation and receptor downregulation induced by formyl-Nle–Leu–Phe. This indicates that formyl peptide receptor may be important in viral infections and that variations in its sequence among individuals may affect their likelihood of viral and bacterial infections.",,"Mills, John S.",,,,
,PMC,A cis-replication element functions in both orientations to enhance replication of Turnip crinkle virus,http://dx.doi.org/10.1016/j.virol.2006.03.051,PMC2937274,,,"Turnip crinkle virus (TCV) (family Tombusviridae, genus Carmovirus) is a positive-sense RNA virus containing a 4054-base genome. Previous results indicated that insertion of Hairpin 4 (H4) into a TCV-associated satellite RNA enhanced replication 6-fold in vivo (P. Nagy, J. Pogany, and A. E. Simon, EMBO J. 18:5653–5665, 1999). A detailed structural and functional analysis of H4 has now been performed to investigate its role in TCV replication. RNA structural probing of H4 in full-length TCV supported the sequence forming hairpin structures in both orientations in vitro. Deletion and mutational analyses determined that H4 is important for efficient accumulation of TCV in protoplasts, with a 98% reduction of genomic RNA levels when H4 was deleted. In vitro transcription using p88 [the TCV RNA-dependent RNA polymerase] demonstrated that H4 in its plus-sense orientation [H4(+)] caused a nearly 2-fold increase in RNA synthesis from a core hairpin promoter located on TCV plus-strands. H4 in its minus-sense orientation [H4(−)] stimulated RNA synthesis by 100-fold from a linear minus-strand promoter. Gel mobility shift assays indicated that p88 binds H4(+) and H4(−) with equal affinity, which was substantially greater than the binding affinity to the core promoters. These results support roles for H4(+) and H4(−) in TCV replication by enhancing syntheses of both strands through attracting the RdRp to the template.",,"['Sun, Xiaoping', 'Simon, Anne E.']",,,,
,PMC,Lee Jong-wook,,PMC1473054,,,Director general of the World Health Organization,,"Day, Michael",,,,
,PMC,Bats and human emerging diseases,http://dx.doi.org/10.1017/S0950268806006674,PMC2870500,,,,,"BENNETT, M.",,,,
,PMC,Index of Authors,,PMC1606634,,,,,,,,,
,PMC,Loss of Angiotensin-Converting Enzyme-2 Leads to the Late Development of Angiotensin II-Dependent Glomerulosclerosis,http://dx.doi.org/10.2353/ajpath.2006.051091,PMC1606622,,,"Angiotensin-converting enzyme-2 (ACE2), a membrane-bound carboxymonopeptidase highly expressed in the kidney, functions as a negative regulator of the renin-angiotensin system. Here we report early accumulation of fibrillar collagen in the glomerular mesangium of male ACE2 mutant (ACE2(−/y)) mice followed by development of glomerulosclerosis by 12 months of age whereas female ACE2 mutant (ACE2(−/−)) mice were relatively protected. Progressive kidney injury was associated with increased deposition of collagen I, collagen III and fibronectin in the glomeruli and increased urinary albumin excretion compared to age-matched control mice. These structural and functional changes in the glomeruli of male ACE2 mutant mice were prevented by treatment with the angiotensin II type-1 receptor antagonist irbesartan. Loss of ACE2 was associated with a marked increase in renal lipid peroxidation product formation and activation of mitogen-activated protein kinase and extracellular signal-regulated kinases 1 and 2 in glomeruli, events that are also prevented by angiotensin II type-1 receptor blockade. We conclude that deletion of the ACE2 gene leads to the development of angiotensin II-dependent glomerular injury in male mice. These findings have important implications for our understanding of ACE2, the renin-angiotensin system, and gender in renal injury, with ACE2 likely to be an important therapeutic target in kidney disease.",,"['Oudit, Gavin Y.', 'Herzenberg, Andrew M.', 'Kassiri, Zamaneh', 'Wong, Denise', 'Reich, Heather', 'Khokha, Rama', 'Crackower, Michael A.', 'Backx, Peter H.', 'Penninger, Josef M.', 'Scholey, James W.']",,,,
,PMC,Index of Subjects,,PMC1606620,,,,,,,,,
,PMC,Inhibition of Human Coronavirus NL63 Infection at Early Stages of the Replication Cycle,http://dx.doi.org/10.1128/AAC.01598-05,PMC1479111,,,"Human coronavirus NL63 (HCoV-NL63), a recently discovered member of the Coronaviridae family, has spread worldwide and is associated with acute respiratory illness in young children and elderly and immunocompromised persons. Further analysis of HCoV-NL63 pathogenicity seems warranted, in particular because the virus uses the same cellular receptor as severe acute respiratory syndrome-associated coronavirus. As there is currently no HCoV-NL63-specific and effective vaccine or drug therapy available, we evaluated several existing antiviral drugs and new synthetic compounds as inhibitors of HCoV-NL63, targeting multiple stages of the replication cycle. Of the 28 compounds that we tested, 6 potently inhibited HCoV-NL63 at early steps of the replication cycle. Intravenous immunoglobulins, heptad repeat 2 peptide, small interfering RNA1 (siRNA1), siRNA2, β-d-N(4)-hydroxycytidine, and 6-azauridine showed 50% inhibitory concentrations of 125 μg/ml, 2 μM, 5 nM, 3 nM, 400 nM, and 32 nM, respectively, and low 50% cytotoxicity concentrations (>10 mg/ml, >40 μM, >200 nM, >200 nM, >100 μM, and 80 μM, respectively). These agents may be investigated further for the treatment of coronavirus infections.",,"['Pyrc, Krzysztof', 'Bosch, Berend Jan', 'Berkhout, Ben', 'Jebbink, Maarten F.', 'Dijkman, Ronald', 'Rottier, Peter', 'van der Hoek, Lia']",,,,
,PMC,Probing genomic diversity and evolution of Escherichia coli O157 by single nucleotide polymorphisms,http://dx.doi.org/10.1101/gr.4759706,PMC1473186,,,"Infections by Shiga toxin-producing Escherichia coli O157:H7 (STEC O157) are the predominant cause of bloody diarrhea and hemolytic uremic syndrome in the United States. In silico comparison of the two complete STEC O157 genomes (Sakai and EDL933) revealed a strikingly high level of sequence identity in orthologous protein-coding genes, limiting the use of nucleotide sequences to study the evolution and epidemiology of this bacterial pathogen. To systematically examine single nucleotide polymorphisms (SNPs) at a genome scale, we designed comparative genome sequencing microarrays and analyzed 1199 chromosomal genes (a total of 1,167,948 bp) and 92,721 bp of the large virulence plasmid (pO157) of eleven outbreak-associated STEC O157 strains. We discovered 906 SNPs in 523 chromosomal genes and observed a high level of DNA polymorphisms among the pO157 plasmids. Based on a uniform rate of synonymous substitution for Escherichia coli and Salmonella enterica (4.7 × 10(−9) per site per year), we estimate that the most recent common ancestor of the contemporary β-glucuronidase-negative, non-sorbitolfermenting STEC O157 strains existed ca. 40 thousand years ago. The phylogeny of the STEC O157 strains based on the informative synonymous SNPs was compared to the maximum parsimony trees inferred from pulsed-field gel electrophoresis and multilocus variable numbers of tandem repeats analysis. The topological discrepancies indicate that, in contrast to the synonymous mutations, parts of STEC O157 genomes have evolved through different mechanisms with highly variable divergence rates. The SNP loci reported here will provide useful genetic markers for developing high-throughput methods for fine-resolution genotyping of STEC O157. Functional characterization of nucleotide polymorphisms should shed new insights on the evolution, epidemiology, and pathogenesis of STEC O157 and related pathogens.",,"['Zhang, Wei', 'Qi, Weihong', 'Albert, Thomas J.', 'Motiwala, Alifiya S.', 'Alland, David', 'Hyytia-Trees, Eija K.', 'Ribot, Efrain M.', 'Fields, Patricia I.', 'Whittam, Thomas S.', 'Swaminathan, Bala']",,,,
,PMC,Combining Multiplex Reverse Transcription-PCR and a Diagnostic Microarray To Detect and Differentiate Enterovirus 71 and Coxsackievirus A16,http://dx.doi.org/10.1128/JCM.02393-05,PMC1489440,,,"Cluster A enteroviruses, including enterovirus 71 (EV71) and coxsackievirus A16 (CA16), are known to cause hand-foot-and-mouth disease (HFMD). Despite the close genetic relationship between these two viruses, EV71 is generally known to be a more perpetuating pathogen involved in severe clinical manifestations and deaths. While the serotyping of enteroviruses is mostly done by conventional immunological methods, many clinical isolates remain unclassifiable due to the limited number of antibodies against enterovirus surface proteins. Array-based assays are able to detect several serotypes with high accuracy. We combined an enterovirus microarray with multiplex reverse transcription-PCR to try to develop a method of sensitively and accurately detecting and differentiating EV71 and CA16. In an effort to design serotype-specific probes for detection of the virus, we first did an elaborate bioinformatic analysis of the sequence database derived from different enterovirus serotypes. We then constructed a microarray using 60-mer degenerate oligonucleotide probes covalently bound to array slides. Using this enterovirus microarray to study 144 clinical specimens from patients infected with HFMD or suspected to have HFMD, we found that it had a diagnostic accuracy of 92.0% for EV71 and 95.8% for CA16. Diagnostic accuracy for other enteroviruses (non-EV71 or -CA16) was 92.0%. All specimens were analyzed in parallel by real-time PCR and subsequently confirmed by neutralization tests. This highly sensitive array-based assay may become a useful alternative in clinical diagnostics of EV71 and CA16.",,"['Chen, Tsan-Chi', 'Chen, Guang-Wu', 'Hsiung, Chao Agnes', 'Yang, Jyh-Yuan', 'Shih, Shin-Ru', 'Lai, Yiu-Kay', 'Juang, Jyh-Lyh']",,,,
,PMC,Coronavirus HKU1 and Other Coronavirus Infections in Hong Kong,http://dx.doi.org/10.1128/JCM.02614-05,PMC1489438,,,"We have recently described the discovery of a novel coronavirus, coronavirus HKU1 (CoV-HKU1), associated with community-acquired pneumonia. However, the clinical spectrum of disease and the epidemiology of CoV-HKU1 infections in relation to infections with other respiratory viruses are unknown. In this 12-month prospective study, 4,181 nasopharyngeal aspirates from patients with acute respiratory tract infections were subjected to reverse transcription-PCRs specific for CoV-HKU1 and human coronaviruses NL63 (HCoV-NL63), OC43 (HCoV-OC43), and 229E (HCoV-229E). Coronaviruses were detected in 87 (2.1%) patients, with 13 (0.3%) positive for CoV-HKU1, 17 (0.4%) positive for HCoV-NL63, 53 (1.3%) positive for HCoV-OC43, and 4 (0.1%) positive for HCoV-229E. Of the 13 patients with CoV-HKU1 infections, 11 were children and 8 had underlying diseases. Similar to the case for other coronaviruses, upper respiratory infection was the most common presentation of CoV-HKU1 infections, although pneumonia, acute bronchiolitis, and asthmatic exacerbation also occurred. Despite a shorter duration of fever (mean, 1.7 days) and no difference in maximum temperature in children with CoV-HKU1 infections compared to patients with most other respiratory virus infections, a high incidence of febrile seizures (50%) was noted, which was significantly higher than those for HCoV-OC43 (14%), adenovirus (9%), human parainfluenza virus 1 (0%), and respiratory syncytial virus (8%) infections. CoV-HKU1 and HCoV-OC43 infections peaked in winter, although cases of the former also occurred in spring to early summer. This is in contrast to HCoV-NL63 infections, which mainly occurred in early summer and autumn but were absent in winter. Two genotypes of CoV-HKU1 cocirculated during the study period. Continuous studies over a longer period are warranted to ascertain the seasonal variation and relative importance of the different coronaviruses. Similar studies in other countries are required to better determine the epidemiology and genetic diversity of CoV-HKU1.",,"['Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Yip, Cyril C. Y.', 'Tse, Herman', 'Tsoi, Hoi-wah', 'Cheng, Vincent C. C.', 'Lee, Paul', 'Tang, Bone S. F.', 'Cheung, Chris H. Y.', 'Lee, Rodney A.', 'So, Lok-yee', 'Lau, Yu-lung', 'Chan, Kwok-hung', 'Yuen, Kwok-yung']",,,,
,PMC,Molecular Mimicry Revisited: Gut Bacteria and Multiple Sclerosis,http://dx.doi.org/10.1128/JCM.02532-05,PMC1489420,,,"Molecular mimicry is a possible explanation for autoimmune side effects of microorganism infections. Protein sequences from a particular microorganism are compared to known autoimmune immunogens. For diseases such as multiple sclerosis (MS), where the infectious agent is unknown, guesses to its identity are made. Mimics are assumed to be rare. This study takes a radically different approach. Reported sequences from all known human bacterial and viral agents were searched for autoimmune immunogen mimics. Three encephalitogenic peptides, whose autoimmune requirements have been studied extensively, were selected for comparison. Mimics were seen in a wide variety of organisms. For each immunogen, the mimics were found predominantly in nonpathogenic gut bacteria. Since the three immunogens used in this study are related to MS, it is suggested that a microorganism responsible for autoimmune activity in MS could be a normally occurring gut bacterium. This would explain many of the peculiar MS epidemiological data and why no infective agent has been identified for MS and supports recently found MS gut metabolism abnormalities.",,"Westall, Fred C.",,,,
,PMC,Rotavirus NSP4 Induces a Novel Vesicular Compartment Regulated by Calcium and Associated with Viroplasms,http://dx.doi.org/10.1128/JVI.02167-05,PMC1472611,,,"Rotavirus is a major cause of infantile viral gastroenteritis. Rotavirus nonstructural protein 4 (NSP4) has pleiotropic properties and functions in viral morphogenesis as well as pathogenesis. Recent reports show that the inhibition of NSP4 expression by small interfering RNAs leads to alteration of the production and distribution of other viral proteins and mRNA synthesis, suggesting that NSP4 also affects virus replication by unknown mechanisms. This report describes studies aimed at correlating the localization of intracellular NSP4 in cells with its functions. To be able to follow the localization of NSP4, we fused the C terminus of full-length NSP4 with the enhanced green fluorescent protein (EGFP) and expressed this fusion protein inducibly in a HEK 293-based cell line to avoid possible cytotoxicity. NSP4-EGFP was initially localized in the endoplasmic reticulum (ER) as documented by Endo H-sensitive glycosylation and colocalization with ER marker proteins. Only a small fraction of NSP4-EGFP colocalized with the ER-Golgi intermediate compartment (ERGIC) marker ERGIC-53. NSP4-EGFP did not enter the Golgi apparatus, in agreement with the Endo H sensitivity and a previous report that secretion of an NSP4 cleavage product generated in rotavirus-infected cells is not inhibited by brefeldin A. A significant population of expressed NSP4-EGFP was distributed in novel vesicular structures throughout the cytoplasm, not colocalizing with ER, ERGIC, Golgi, endosomal, or lysosomal markers, thus diverging from known biosynthetic pathways. The appearance of vesicular NSP4-EGFP was dependent on intracellular calcium levels, and vesicular NSP4-EGFP colocalized with the autophagosomal marker LC3. In rotavirus-infected cells, NSP4 colocalized with LC3 in cap-like structures associated with viroplasms, the site of nascent viral RNA replication, suggesting a possible new mechanism for the involvement of NSP4 in virus replication.",,"['Berkova, Z.', 'Crawford, S. E.', 'Trugnan, G.', 'Yoshimori, T.', 'Morris, A. P.', 'Estes, M. K.']",,,,
,PMC,Ultrastructure and Origin of Membrane Vesicles Associated with the Severe Acute Respiratory Syndrome Coronavirus Replication Complex,http://dx.doi.org/10.1128/JVI.02501-05,PMC1472606,,,"The RNA replication complexes of mammalian positive-stranded RNA viruses are generally associated with (modified) intracellular membranes, a feature thought to be important for creating an environment suitable for viral RNA synthesis, recruitment of host components, and possibly evasion of host defense mechanisms. Here, using a panel of replicase-specific antisera, we have analyzed the earlier stages of severe acute respiratory syndrome coronavirus (SARS-CoV) infection in Vero E6 cells, in particular focusing on the subcellular localization of the replicase and the ultrastructure of the associated membranes. Confocal immunofluorescence microscopy demonstrated the colocalization, throughout infection, of replicase cleavage products containing different key enzymes for SARS-CoV replication. Electron microscopy revealed the early formation and accumulation of typical double-membrane vesicles, which probably carry the viral replication complex. The vesicles appear to be fragile, and their preservation was significantly improved by using cryofixation protocols and freeze substitution methods. In immunoelectron microscopy, the virus-induced vesicles could be labeled with replicase-specific antibodies. Opposite to what was described for mouse hepatitis virus, we did not observe the late relocalization of specific replicase subunits to the presumed site of virus assembly, which was labeled using an antiserum against the viral membrane protein. This conclusion was further supported using organelle-specific marker proteins and electron microscopy. Similar morphological studies and labeling experiments argued against the previously proposed involvement of the autophagic pathway as the source for the vesicles with which the replicase is associated and instead suggested the endoplasmic reticulum to be the most likely donor of the membranes that carry the SARS-CoV replication complex.",,"['Snijder, Eric J.', 'van der Meer, Yvonne', 'Zevenhoven-Dobbe, Jessika', 'Onderwater, Jos J. M.', 'van der Meulen, Jannes', 'Koerten, Henk K.', 'Mommaas, A. Mieke']",,,,
,PMC,Identification of an N-Terminal Trimeric Coiled-Coil Core within Arenavirus Glycoprotein 2 Permits Assignment to Class I Viral Fusion Proteins,http://dx.doi.org/10.1128/JVI.00008-06,PMC1472595,,,"The lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) consists of the transmembrane subunit GP-2 and the receptor binding subunit GP-1. Both are synthesized as one precursor protein and stay noncovalently attached after cleavage. In this study, we determined the oligomeric state of the LCMV GP and expressed it in two different conformations suitable for structural analysis. Sequence analysis of GP-2 identified a trimeric heptad repeat pattern containing an N-terminal α-helix. An α-helical peptide matching this region formed a stable oligomer as revealed by gel filtration chromatography and dynamic light scattering. In contrast, a second α-helical peptide corresponding to a predicted C-terminal α-helix within GP-2 did not oligomerize. Refolding of the complete GP-2 ectodomain revealed trimeric all-alpha complexes probably representing the six-helix bundle state that is considered a hallmark of class I viral fusion proteins. Based on these results, we generated a construct consisting of the complete uncleavable LCMV GP ectodomain fused C-terminally to the trimeric motif of fibritin. Gel filtration analysis of the secreted fusion protein identified two complexes of ∼230 and ∼440 kDa. Both complexes bound to a set of conformational and linear antibodies. Cross-linking confirmed the 230-kDa complex to be a trimer. The 440-kDa complexes were found to represent disulfide-linked pairs of trimers, since partial reduction converted them to a complex species migrating at 250 kDa. By electron microscopy, the 230-kDa complexes appeared as single spherical particles and showed no signs of rosette formation. Our results clearly demonstrate that the arenavirus GP is a trimer and must be considered a member of the class I viral fusion protein family.",,"['Eschli, Bruno', 'Quirin, Katharina', 'Wepf, Alexander', 'Weber, Jacqueline', 'Zinkernagel, Rolf', 'Hengartner, Hans']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.00817-06,PMC1472587,,,,,,,,,
,PMC,Antigenic and Immunogenic Characterization of Recombinant Baculovirus-Expressed Severe Acute Respiratory Syndrome Coronavirus Spike Protein: Implication for Vaccine Design,http://dx.doi.org/10.1128/JVI.00083-06,PMC1472569,,,"The spike (S) glycoprotein of severe acute respiratory syndrome coronavirus (SARS-CoV) mediates the receptor interaction and immune recognition and is considered a major target for vaccine design. However, its antigenic and immunogenic properties remain to be elucidated. In this study, we immunized mice with full-length S protein (FL-S) or its extracellular domain (EC-S) expressed by recombinant baculoviruses in insect cells. We found that the immunized mice developed high titers of anti-S antibodies with potent neutralizing activities against SARS pseudoviruses constructed with the S proteins of Tor2, GD03T13, and SZ3, the representative strains of 2002 to 2003 and 2003 to 2004 human SARS-CoV and palm civet SARS-CoV, respectively. These data suggest that the recombinant baculovirus-expressed S protein vaccines possess excellent immunogenicity, thereby inducing highly potent neutralizing responses against human and animal SARS-CoV variants. The antigenic structure of the S protein was characterized by a panel of 38 monoclonal antibodies (MAbs) isolated from the immunized mice. The epitopes of most anti-S MAbs (32 of 38) were localized within the S1 domain, and those of the remaining 6 MAbs were mapped to the S2 domain. Among the anti-S1 MAbs, 17 MAbs targeted the N-terminal region (amino acids [aa] 12 to 327), 9 MAbs recognized the receptor-binding domain (RBD; aa 318 to 510), and 6 MAbs reacted with the C-terminal region of S1 domain that contains the major immunodominant site (aa 528 to 635). Strikingly, all of the RBD-specific MAbs had potent neutralizing activity, 6 of which efficiently blocked the receptor binding, confirming that the RBD contains the main neutralizing epitopes and that blockage of the receptor association is the major mechanism of SARS-CoV neutralization. Five MAbs specific for the S1 N-terminal region exhibited moderate neutralizing activity, but none of the MAbs reacting with the S2 domain and the major immunodominant site in S1 showed neutralizing activity. All of the neutralizing MAbs recognize conformational epitopes. These data provide important information for understanding the antigenicity and immunogenicity of S protein and for designing SARS vaccines. This panel of anti-S MAbs can be used as tools for studying the structure and function of the SARS-CoV S protein.",,"['He, Yuxian', 'Li, Jingjing', 'Heck, Susanne', 'Lustigman, Sara', 'Jiang, Shibo']",,,,
,PMC,Endosomal Proteolysis by Cathepsins Is Necessary for Murine Coronavirus Mouse Hepatitis Virus Type 2 Spike-Mediated Entry,http://dx.doi.org/10.1128/JVI.00442-06,PMC1472567,,,"Most strains of murine coronavirus mouse hepatitis virus (MHV) express a cleavable spike glycoprotein that mediates viral entry and pH-independent cell-cell fusion. The MHV type 2 (MHV-2) strain of murine coronavirus differs from other strains in that it expresses an uncleaved spike and cannot induce cell-cell fusion at neutral pH values. We show here that while infection of the prototype MHV-A59 strain is not sensitive to pretreatment with lysosomotropic agents, MHV-2 replication is significantly inhibited by these agents. By use of an A59/MHV-2 chimeric virus, the susceptibility to lysosomotropic agents is mapped to the MHV-2 spike, suggesting a requirement of acidification of endosomes for MHV-2 spike-mediated entry. However, acidification is likely not a direct trigger for MHV-2 spike-mediated membrane fusion, as low-pH treatment is unable to overcome ammonium chloride inhibition, and it also cannot induce cell-cell fusion between MHV-2-infected cells. In contrast, trypsin treatment can both overcome ammonium chloride inhibition and promote cell-cell fusion. Inhibitors of the endosomal cysteine proteases cathepsin B and cathepsin L greatly reduce MHV-2 spike-mediated entry, while they have little effect on A59 entry, suggesting that there is a proteolytic step in MHV-2 entry. Finally, a recombinant virus expressing a cleaved MHV-2 spike has the ability to induce cell-cell fusion at neutral pH values and does not require low pH and endosomal cathepsins during infection. These studies demonstrate that endosomal proteolysis by cathepsins is necessary for MHV-2 spike-mediated entry; this is similar to the entry pathway recently described for severe acute respiratory syndrome coronavirus and indicates that coronaviruses may use multiple pathways for entry.",,"['Qiu, Zhaozhu', 'Hingley, Susan T.', 'Simmons, Graham', 'Yu, Christopher', 'Das Sarma, Jayasri', 'Bates, Paul', 'Weiss, Susan R.']",,,,
,PMC,Nuclear Localization of Flavivirus RNA Synthesis in Infected Cells,http://dx.doi.org/10.1128/JVI.01982-05,PMC1472159,,,"Flaviviral replication is believed to be exclusively cytoplasmic, occurring within virus-induced membrane-bound replication complexes in the host cytoplasm. Here we show that a significant proportion (20%) of the total RNA-dependent RNA polymerase (RdRp) activity from cells infected with West Nile virus, Japanese encephalitis virus (JEV), and dengue virus is resident within the nucleus. Consistent with this, the major replicase proteins NS3 and NS5 of JEV also localized within the nucleus. NS5 was found distributed throughout the nucleoplasm, but NS3 was present at sites of active flaviviral RNA synthesis, colocalizing with NS5, and visible as distinct foci along the inner periphery of the nucleus by confocal and immunoelectron microscopy. Both these viral replicase proteins were also present in the nuclear matrix, colocalizing with the peripheral lamina, and revealed a well-entrenched nuclear location for the viral replication complex. In keeping with this observation, antibodies to either NS3 or NS5 coimmunoprecipitated the other protein from isolated nuclei along with newly synthesized viral RNA. Taken together these data suggest an absolute requirement for both of the replicase proteins for nucleus-localized synthesis of flavivirus RNA. Thus, we conclusively demonstrate for the first time that the host cell nucleus functions as an additional site for the presence of functionally active flaviviral replicase complex.",,"['Uchil, Pradeep Devappa', 'Kumar, Anil V. A.', 'Satchidanandam, Vijaya']",,,,
,PMC,Molecular Determinants of Substrate Specificity for Semliki Forest Virus Nonstructural Protease,http://dx.doi.org/10.1128/JVI.00229-06,PMC1472149,,,"The C-terminal cysteine protease domain of Semliki Forest virus nonstructural protein 2 (nsP2) regulates the virus life cycle by sequentially cleaving at three specific sites within the virus-encoded replicase polyprotein P1234. The site between nsP3 and nsP4 (the 3/4 site) is cleaved most efficiently. Analysis of Semliki Forest virus-specific cleavage sites with shuffled N-terminal and C-terminal half-sites showed that the main determinants of cleavage efficiency are located in the region preceding the cleavage site. Random mutagenesis analysis revealed that amino acid residues in positions P4, P3, P2, and P1 of the 3/4 cleavage site cannot tolerate much variation, whereas in the P5 position most residues were permitted. When mutations affecting cleavage efficiency were introduced into the 2/3 and 3/4 cleavage sites, the resulting viruses remained viable but had similar defects in P1234 processing as observed in the in vitro assay. Complete blockage of the 3/4 cleavage was found to be lethal. The amino acid in position P1′ had a significant effect on cleavage efficiency, and in this regard the protease markedly preferred a glycine residue over the tyrosine natively present in the 3/4 site. Therefore, the cleavage sites represent a compromise between protease recognition and other requirements of the virus life cycle. The protease recognizes at least residues P4 to P1′, and the P4 arginine residue plays an important role in the fast cleavage of the 3/4 site.",,"['Lulla, Aleksei', 'Lulla, Valeria', 'Tints, Kairit', 'Ahola, Tero', 'Merits, Andres']",,,,
,PMC,Restoration in vivo of defective hepatitis delta virus RNA genomes,http://dx.doi.org/10.1261/rna.2328806,PMC1464851,,,"The 1679-nt single-stranded RNA genome of hepatitis delta virus (HDV) is circular in conformation. It is able to fold into an unbranched rodlike structure via intramolecular base-pairing. This RNA is replicated by host RNA polymerase II (Pol II). Such transcription is unique, because Pol II is known only for its ability to act on DNA templates. The present study addressed the ability of the HDV RNA replication to tolerate insertions of up to 1000 nt of non-HDV sequence either at an end of the rodlike RNA structure or at a site embedded within the rod. The insertions did not interfere with the ability of primary transcripts to be processed in vivo by ribozyme cleavage and ligation. The insertions greatly reduced the ability of genomes to replicate. However, when total RNA from such transfected cells was used to transfect new recipient cells, replicating HDV RNAs could be detected by Northern analyses. The size of the emerged RNAs was consistent with loss of the inserted sequences. RT-PCR, cloning, and sequencing showed that recovery involved removal of inserted sequences with or without small deletions of adjacent RNA sequences. Such restoration of the RNA genome is consistent with a model requiring intramolecular template-switching (RNA recombination) during RNA-directed transcription, in combination with biological selection for maintenance of the rodlike structure of the template.",,"['Gudima, Severin O.', 'Chang, Jinhong', 'Taylor, John M.']",,,,
,PMC,pH-dependence of intermediate steps of membrane fusion induced by the influenza fusion peptide,http://dx.doi.org/10.1042/BJ20051920,PMC1482821,,,"Membrane fusion mediated by the influenza-virus fusion protein is activated by low pH via a cascade of reactions. Some processes among them are irreversible, such as helix hairpin formation of the ectodomain, whereas others are reversible, such as exposure of the fusion peptide. Using this property, we attempted to dissect, in temporal order, different stages of the fusion reaction involving the fusion peptide by an acidic–neutral–acidic pH cycle. The fluorescence-quenching data indicated that both insertion depth and self-assembly are pH-reversible. In addition, lipid mixing assay was demonstrated to be arrested by neutral pH. By contrast, membrane leakage was shown to be irreversible with respect to pH. Our results, along with those from other studies on the pH-dependence of membrane fusion, are used to build a model for the virus-mediated fusion event from the perspective of pH-reversibility.",,"['Chang, Ding-Kwo', 'Cheng, Shu-Fang']",,,,
,PMC,pH-Dependent Lytic Peptides Discovered by Phage-Display,http://dx.doi.org/10.1021/bi052488s,PMC2515554,,,"Lipid membranes compartmentalize eukaryotic cells and separate the cell interior from the extracellular milieu. So far, studies of peptide and protein interactions with membranes have largely been limited to naturally occurring peptides or to sequences designed on the basis of structural information and biophysical parameters. To expand on these studies, utilizing a system with minimal assumptions, we used phage-display technology to identify 12 amino-acid-long peptides that bind to liposomes at pH 5.0 but not at pH 7.5. Of the nineteen peptides discovered three were able to cause leakage of liposome contents. Multivalent presentation of these membrane-active peptides by conjugation onto poly(L-Lysine) enhanced their lytic potential. Secondary structures were analyzed by circular dichroism in aqueous 2,2,2-trifluoroethanol and in buffered aqueous solutions, in both the presence and absence of liposomes. Two of the three lytic peptides show alpha helical profiles whereas none of the non-lytic peptides formed stable secondary structures. The diverse characteristics of the peptides identified in this study demonstrate that phage-displayed peptide library screens on lipid membranes result in the discovery of non-classical membrane-active peptides, whose study will provide novel insights into peptide-membrane interactions.",,"['Hirosue, Sachiko', 'Weber, Thomas']",,,,
,PMC,Body consults to balance public health against private rights,,PMC1463921,,,,,"Day, Michael",,,,
,PMC,Managing the effect of TRIPS on availability of priority vaccines.,,PMC2627354,,,"The stated purpose of intellectual property protection is to stimulate innovation. The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) requires all Members of the World Trade Organization (WTO) to enact national laws conferring minimum standards of intellectual property protection by certain deadlines. Critics of the Agreement fear that such action is inconsistent with ensuring access to medicines in the developing world. A WHO convened meeting on intellectual property rights and vaccines in developing countries, on which this paper is based, found no evidence that TRIPS has stimulated innovation in developing market vaccine development (where markets are weak) or that protection of intellectual property rights has had a negative effect on access to vaccines. However, access to future vaccines in the developing world could be threatened by compliance with TRIPS. The management of such threats requires adherence of all countries to the Doha Declaration on TRIPS, and the protections guaranteed by the Agreement itself, vigilance on TRIPS-plus elements of free trade agreements, developing frameworks for licensing and technology transfer, and promoting innovative vaccine development in developing countries. The role of international organizations in defining best practices, dissemination of information, and monitoring TRIPS impact will be crucial to ensuring optimal access to priority new vaccines for the developing world.",,"['Milstien, Julie', 'Kaddar, Miloud']",,,,
,PMC,Access to AIDS medicines stumbles on trade rules.,,PMC2627352,,,,,"Wise, Jacqui",,,,
,PMC,Rich and poor countries divided on patent treaty.,,PMC2627345,,,,,"New, William",,,,
,PMC,Meeting the need for treatment: the initiatives.,,PMC2627344,,,,,"Gerhardsen, Tove Iren S.",,,,
,PMC,A human rights approach to the WHO Model List of Essential Medicines.,,PMC2627340,,,"Since the first WHO Model List of Essential Medicines was adopted in 1977, it has become a popular tool among health professionals and Member States. WHO's joint effort with the United Nations Committee on Economic, Social and Cultural Rights has resulted in the inclusion of access to essential medicines in the core content of the right to health. The Committee states that the right to health contains a series of elements, such as availability, accessibility, acceptability and quality of health goods, services and programmes, which are in line with the WHO statement that essential medicines are intended to be available within the context of health systems in adequate amounts at all times, in the appropriate dosage forms, with assured quality and information, and at a price that the individual and the community can afford. The author considers another perspective by looking at the obligations to respect, protect and fulfil the right to health undertaken by the states adhering to the International Covenant of Economic, Social and Cultural Rights (ICESCR) and explores the relationship between access to medicines, the protection of intellectual property, and human rights.",,"Seuba, Xavier",,,,
,PMC,Protecting traditional knowledge: the San and hoodia.,,PMC2627337,,,,,,,,,
,PMC,A clearing house for diagnostic testing: the solution to ensure access to and use of patented genetic inventions?,,PMC2627336,,,"In genetic diagnostics, the emergence of a so-called ""patent thicket"" is imminent. Such an overlapping set of patent rights may have restrictive effects on further research and development of diagnostic tests, and the provision of clinical diagnostic services. Currently, two models that may facilitate access to and use of patented genetic inventions are attracting much debate in various national and international fora: patent pools and clearing houses. In this article, we explore the concept of clearing houses. Several types of clearing houses are identified. First, we describe and discuss two types that would provide access to information on the patented inventions: the information clearing house and the technology exchange clearing house. Second, three types of clearing houses are analysed that not only offer access to information but also provide an instrument to facilitate the use of the patented inventions: the open access clearing house, the standardized licences clearing house and the royalty collection clearing house. A royalty collection clearing house for genetic diagnostic testing would be the most comprehensive as it would serve several functions: identifying patents and patent claims essential to diagnostic testing, matching licensees with licensors, developing and supplying standardized licences, collecting royalties, monitoring whether users respect licensing conditions, and providing dispute resolution services such as mediation and arbitration. In this way, it might function as an effective model for users to facilitate access to and use of the patented inventions. However, it remains to be seen whether patent holders with a strong patent portfolio will be convinced by the advantages of the royalty collection clearing house and be willing to participate.",,"['van Zimmeren, Esther', 'Verbeure, Birgit', 'Matthijs, Gert', 'Van Overwalle, Geertrui']",,,,
,PMC,Model of a Putative Pore: The Pentameric α-Helical Bundle of SARS Coronavirus E Protein in Lipid Bilayers,http://dx.doi.org/10.1529/biophysj.105.080119,PMC1563757,,,"The coronavirus responsible for the severe acute respiratory syndrome contains a small envelope protein, E, with putative involvement in host apoptosis and virus morphogenesis. To perform these functions, it has been suggested that protein E can form a membrane destabilizing transmembrane (TM) hairpin, or homooligomerize to form a TM pore. Indeed, in a recent study we reported that the α-helical putative transmembrane domain of E protein (ETM) forms several SDS-resistant TM interactions: a dimer, a trimer, and two pentameric forms. Further, these interactions were found to be evolutionarily conserved. Herein, we have studied multiple isotopically labeled ETM peptides reconstituted in model lipid bilayers, using the orientational parameters derived from infrared dichroic data. We show that the topology of ETM is consistent with a regular TM α-helix. Further, the orientational parameters obtained unequivocally correspond to a homopentameric model, by comparison with previous predictions. We have independently confirmed that the full polypeptide of E protein can also aggregate as pentamers after expression in Escherichia coli. This interaction must be stabilized, at least partially, at the TM domain. The model we report for this pentameric α-helical bundle may explain some of the permabilizing properties of protein E, and should be the basis of mutagenesis efforts in future functional studies.",,"['Torres, Jaume', 'Parthasarathy, Krupakar', 'Lin, Xin', 'Saravanan, Rathi', 'Kukol, Andreas', 'Liu, Ding Xiang']",,,,
,PMC,Increasing epidemic surge capacity with home-based hospital                 care,,PMC1531731,,,,,"['Hogg, William', 'Lemelin, Jacques', 'Huston, Patricia', 'Dahrouge, Simone']",,,,
,PMC,Physical Plant Design and Engineering Controls to Reduce Hospital-acquired Infections,,PMC2095066,,,,,"['Conly, JM', 'Johnston, BL']",,,,
,PMC,Surge Capacity and Casualization: Human Resource Issues in the Post-SARS Health System,http://dx.doi.org/10.1007/BF03405592,PMC6975992,,,"In Ontario, the unpredictable funding climate of the 1990s led health care organizations to look for ways to reduce costs. Adopting a just-in-time staffing policy, they employed fewer full-time workers, scheduled part-time workers to work regular shifts, took on more casual staff, and became increasingly reliant on agency nurses and overtime to cover shifts. These policies resulted in higher costs and reduced surge capacity, and placed the health of nurses and patients in jeopardy. Fewer staff meant more overtime. Stress-related absenteeism increased. Some nurses reacted to casualization by working for multiple employers. During the SARS (severe acute respiratory syndrome) epidemic in Toronto, nursing resources were stretched to their limits. An exploratory investigation, based on relevant literature and interviews with 13 nurse administrators who held key positions during the epidemic, confirmed the lack of spare capacity in the health care system and indicated that community and long-term care sectors had less capacity than acute care. Low surge capacity in these sectors increased the vulnerability of the entire health care system. Capacity issues should be addressed as part of a larger human resources initiative to create a more flexible workforce. Since SARS, a number of government and organizational initiatives have been developed to increase nursing capacity.",,"['Baumann, Andrea O.', 'Blythe, Jennifer M.', 'Underwood, Jane M.']",,,,
,PMC,Clinical Proteomics: Present and Future Prospects,,PMC1579414,,,"Advances in proteomics technology offer great promise in the understanding and treatment of the molecular basis of disease. The past decade of proteomics research, the study of dynamic protein expression, post-translational modifications, cellular and sub-cellular protein distribution, and protein-protein interactions, has culminated in the identification of many disease-related biomarkers and potential new drug targets. While proteomics remains the tool of choice for discovery research, new innovations in proteomic technology now offer the potential for proteomic profiling to become standard practice in the clinical laboratory. Indeed, protein profiles can serve as powerful diagnostic markers, and can predict treatment outcome in many diseases, in particular cancer. A number of technical obstacles remain before routine proteomic analysis can be achieved in the clinic; however the standardisation of methodologies and dissemination of proteomic data into publicly available databases is starting to overcome these hurdles. At present the most promising application for proteomics is in the screening of specific subsets of protein biomarkers for certain diseases, rather than large scale full protein profiling. Armed with these technologies the impending era of individualised patient-tailored therapy is imminent. This review summarises the advances in proteomics that has propelled us to this exciting age of clinical proteomics, and highlights the future work that is required for this to become a reality.",,"Verrills, Nicole M",,,,
,PMC,Production of an Anti-Severe Acute Respiratory Syndrome (SARS) Coronavirus Human Monoclonal Antibody Fab Fragment by Using a Combinatorial Immunoglobulin Gene Library Derived from Patients Who Recovered from SARS,http://dx.doi.org/10.1128/CVI.13.5.594-597.2006,PMC1459658,,,"A combinatorial human immunoglobulin gene library was constructed from the peripheral lymphocytes of two patients who recovered from severe acute respiratory syndrome (SARS). The library was screened for the production of Fab antibody fragments to a recombinant spike protein of SARS-associated coronavirus (SARS-CoV). One Fab clone, AS3-3, reacted with the spike protein in an enzyme-linked immunosorbent assay. The dissociation constant of AS3-3 was 1.98 × 10(−8) M. Immunofluorescent microscopy revealed that it reacted with SARS-CoV-infected cells. The library seems to be a potent tool for the production of human antibodies to SARS-CoV.",,"['Liu, Jinye', 'Shao, Hongxia', 'Tao, Yanlin', 'Yang, Bin', 'Qian, Lisheng', 'Yang, Xiaoli', 'Cao, Brian', 'Hu, Gengxi', 'Tachibana, Hiroshi', 'Cheng, Xunjia']",,,,
,PMC,Paediatric emergency department staff perceptions of infection control measures against severe acute respiratory syndrome,http://dx.doi.org/10.1136/emj.2005.026146,PMC2564081,,,"OBJECTIVES: To determine paediatric emergency department (ED) staff perceptions of the effectiveness and practice of infection control measures against a novel virulent pathogen. METHODS: All medical staff of the paediatric ED in a tertiary medical centre completed a written questionnaire near the onset of the severe acute respiratory syndrome (SARS) outbreak. Level of concern regarding SARS, and perceptions of effectiveness and use of infection control measures were assessed on a 5 point scale. Statistical analysis was performed using χ(2) test and one way analysis of variance with significance at p<0.05. RESULTS: Response rate was 97% (116/120). All scores were given out of 5 possible points. Using isolation rooms (mean score 4.6), wearing a mask when examining patients (4.5), and handwashing (4.5) were considered most effective. Staff physicians reported handwashing more than nurses and trainees (4.9 v 4.5 and 4.5, respectively; p<0.05) while other measures were reported equally. Respondents considering SARS a high public health threat reported higher compliance with handwashing (4.8 v 4.4), always wearing a mask (3.9 vs 3.2) and gloves (3.6 v 2.9) in the ED (p<0.05), but not eye protection (3.4 v 3.0), gown use (4.9 v 4.7), or wearing a mask when examining patients (5.0 v 4.8). Staff who considered combined infection control measures effective in protecting patients and healthcare workers did not report increased compliance. CONCLUSIONS: Eye protection was perceived as only moderately effective in protecting against the spread of SARS, and reported compliance was relatively poor among ED staff. Concern of SARS as a public health threat rather than perceived effectiveness of infection control measures appears to have a greater impact on compliance.",,"['Parker, M J', 'Goldman, R D']",,,,
,PMC,Role of natural interferon-producing cells and T lymphocytes in porcine monocyte-derived dendritic cell maturation,http://dx.doi.org/10.1111/j.1365-2567.2006.02343.x,PMC1782262,,,"Maturation of dendritic cells (DC) is a key immunological process regulating immune responses to pathogens and vaccines, as well as tolerance and autoimmune processes. Consequently, the regulation of DC maturation should reflect these multifaceted immunological processes. In the present study, we have defined the role of particular cytokines, Toll-like receptor (TLR) ligands and T lymphocytes in the porcine monocyte-derived DC (MoDC). Interferon-α (IFN-α) alone was a poor inducer of MoDC maturation, but in association with tumour necrosis factor-α (TNF-α), or TLR ligands such as lipopolysaccharide and polyinosinic-polycytidylic acid I:C, an up-regulation of major histocompatibility complex II and CD80/86 expression was noted, along with reduced endocytic activity. In contrast, TNF-α alone or in combination with the TLR ligands was a poor inducer of DC maturation, but co-operated with T-lymphocytes in the presence of antigen to induce DC maturation. Natural interferon producing cells (NIPC, or plasmacytoid DCs) represent a danger-recognition system of the immune defences, and can respond to viruses not otherwise recognized as posing a danger. Indeed, MoDC did not respond to transmissible gastroenteritis virus (TGEV), whereas NIPC produced high levels of IFN-α and TNF-α after TGEV stimulation. Moreover, supernatants from the stimulated NIPC induced maturation in MoDCs. These matured MoDCs displayed an enhanced ability to present antigen to and thus stimulate T cells. Taken together, the present work demonstrates that maturation of MoDC not only results from TLR signalling, but can require co-operation with various cell types – principally NIPC and activated T cells – which would reflect the particular immunological situation.",,"['Guzylack-Piriou, Laurence', 'Piersma, Sytse', 'McCullough, Kenneth', 'Summerfield, Artur']",,,,
,PMC,Molecular Epidemiology of Bovine Coronavirus on the Basis of Comparative Analyses of the S Gene,http://dx.doi.org/10.1128/JCM.44.5.1924.2006,PMC1479183,,,,,"['Liu, Lihong', 'Hägglund, Sara', 'Hakhverdyan, Mikhayil', 'Alenius, Stefan', 'Larson, Lars Erik', 'Belák, Sándor']",,,,
,PMC,Specific epitopes of the structural and hypothetical proteins elicit variable humoral responses in SARS patients,http://dx.doi.org/10.1136/jcp.2005.029868,PMC1860290,,,"BACKGROUND: Severe acute respiratory syndrome (SARS) is an infectious disease which was caused by a novel coronavirus (SARS‐CoV). SARS has caused an outbreak in the world during 2003 and 2004, with 8098 individuals being infected and a death toll of 774 in 28 regions around the world. Specific humoral responses to viral infection remain unclear. OBJECTIVE: To analyse the antigenicity of the SARS‐CoV genome and identify potential antigenic epitopes in the structural proteins. METHODS: Potential antigenic epitopes were identified in the structural proteins (nucleocapsid, membrane, spike, and small envelope proteins) and hypothetical proteins (SARS3a, 3b, 6, 7a, and 9b) that are specific for SARS‐CoV. A peptide chip platform was created and the profiles of antibodies to these epitopes were investigated in 59 different SARS patients' sera obtained 6–103 days after the onset of the illness. Serial sera from five additional patients were also studied. RESULTS: Epitopes at the N‐terminus of the membrane protein and the C‐terminus of nucleocapsid protein elicited strong antibody responses. Epitopes on the spike protein were only moderately immunogenic but the effects were persistent. Antibodies were also detected for some putative proteins, noticeably the C‐termini of SARS3a and SARS6. CONCLUSIONS: Important epitopes of the SARS‐CoV genome that may serve as potential markers for the viral infection are identified. These specific antigenic sites may also be important for vaccine development against this new fatal infectious disease.",,"['Chow, S C S', 'Ho, C Y S', 'Tam, T T Y', 'Wu, C', 'Cheung, T', 'Chan, P K S', 'Ng, M H L', 'Hui, P K', 'Ng, H K', 'Au, D M Y', 'Lo, A W I']",,,,
,PMC,SARS-CoV Virus-Host Interactions and Comparative Etiologies of Acute Respiratory Distress Syndrome as Determined by Transcriptional and Cytokine Profiling of Formalin-Fixed Paraffin-Embedded Tissues,http://dx.doi.org/10.1089/jir.2006.26.309,PMC4496958,,,"These studies attempt to understand more fully the host response and pathogenesis associated with severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) by monitoring gene expression using formalin-fixed paraffin-embedded (FFPE) pulmonary autopsy tissues. These tissues were from patients in different hospitals in Singapore who were diagnosed with various microbial infections, including SARS-CoV, that caused acute respiratory distress syndrome (ARDS). Global expression patterns showed limited correlation between end-stage ARDS and the initiating pathogen, but when focusing on a subset of genes implicated in pulmonary pathogenesis, molecular signatures of pulmonary disease were obtained and appeared to be influenced by preexisting pulmonary complications and also bacterial components of infection. Many factors detected during pulmonary damage and repair, such as extracellular matrix (ECM) components, transforming growth factor (TGF) enhancers, acute-phase proteins, and antioxidants, were included in the molecular profiles of these ARDS lung tissues. In addition, differential expression of cytokines within these pulmonary tissues were observed, including notable genes involved in the interferon (IFN) pathway, such as Stat1, IFN regulatory factor-1 (IRF-1), interleukin-6 (IL-6), IL-8, and IL-18, that are often characterized as elevated in ARDS patients.",,"['Baas, Tracey', 'Taubenberger, Jeffery K.', 'Chong, Pek Yoon', 'Chui, Paul', 'Katze, Michael G.']",,,,
,PMC,Human Rhinovirus Attenuates the Type I Interferon Response by Disrupting Activation of Interferon Regulatory Factor 3,http://dx.doi.org/10.1128/JVI.80.10.5021-5031.2006,PMC1472094,,,"The type I interferon (IFN) response requires the coordinated activation of the latent transcription factors NF-κB, interferon regulatory factor 3 (IRF-3), and ATF-2, which in turn activate transcription from the IFN-β promoter. Synthesis and subsequent secretion of IFN-β activate the Jak/STAT signaling pathway, resulting in the transcriptional induction of the full spectrum of antiviral gene products. We utilized high-density microarrays to examine the transcriptional response to rhinovirus type 14 (RV14) infection in HeLa cells, with particular emphasis on the type I interferon response and production of IFN-β. We found that, although RV14 infection results in altered levels of a wide variety of host mRNAs, induction of IFN-β mRNA or activation of the Jak/STAT pathway is not seen. Prior work has shown, and our results have confirmed, that NF-κB and ATF-2 are activated following infection. Since many viruses are known to target IRF-3 to inhibit the induction of IFN-β mRNA, we analyzed the status of IRF-3 in infected cells. IRF-3 was translocated to the nucleus and phosphorylated in RV14-infected cells. Despite this apparent activation, very little homodimerization of IRF-3 was evident following infection. Similar results in A549 lung alveolar epithelial cells demonstrated the biological relevance of these findings to RV14 pathogenesis. In addition, prior infection of cells with RV14 prevented the induction of IFN-β mRNA following treatment with double-stranded RNA, indicating that RV14 encodes an activity that specifically inhibits this innate host defense pathway. Collectively, these results indicate that RV14 infection inhibits the host type I interferon response by interfering with IRF-3 activation.",,"['Peng, Tao', 'Kotla, Swathi', 'Bumgarner, Roger E.', 'Gustin, Kurt E.']",,,,
,PMC,DC-SIGN Facilitates Fusion of Dendritic Cells with Human T-Cell Leukemia Virus Type 1-Infected Cells,http://dx.doi.org/10.1128/JVI.80.10.4771-4780.2006,PMC1472089,,,"Interactions between the oncogenic retrovirus human T-cell leukemia virus type 1 (HTLV-1) and dendritic cells (DCs) are poorly characterized. We show here that monocyte-derived DCs form syncytia and are infected upon coculture with HTLV-1-infected lymphocytes. We examined the role of DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), a C-type lectin expressed in DCs, in HTLV-1-induced syncytium formation. DC-SIGN is known to bind with high affinity to various viral envelope glycoproteins, including human immunodeficiency virus (HIV) and hepatitis C virus, as well as to the cellular receptors ICAM-2 and ICAM-3. After cocultivating DCs and HTLV-1-infected cells, we found that anti-DC-SIGN monoclonal antibodies (MAbs) were able to decrease the number and size of HTLV-1-induced syncytia. Moreover, expression of the lectin in epithelial-cell lines dramatically enhanced the ability to fuse with HTLV-1-positive cells. Interestingly, in contrast to the envelope (Env) glycoproteins of HIV and other viruses, that of HTLV-1 does not bind directly to DC-SIGN. The facilitating role of the lectin in HTLV-1 syncytium formation is mediated by its interaction with ICAM-2 and ICAM-3, as demonstrated by use of MAbs directed against these adhesion molecules. Altogether, our results indicate that DC-SIGN facilitates HTLV-1 infection and fusion of DCs through an ICAM-dependent mechanism.",,"['Ceccaldi, Pierre-Emmanuel', 'Delebecque, Frédéric', 'Prevost, Marie-Christine', 'Moris, Arnaud', 'Abastado, Jean-Pierre', 'Gessain, Antoine', 'Schwartz, Olivier', 'Ozden, Simona']",,,,
,PMC,Identification and Characterization of Novel Adeno-Associated Virus Isolates in ATCC Virus Stocks,http://dx.doi.org/10.1128/JVI.80.10.5082-5085.2006,PMC1472088,,,"Adeno-associated viruses (AAVs) depend on a helper virus for efficient replication. To identify novel AAV isolates, we screened a diverse set of virus isolates for the presence of AAV DNA. AAVs found in 10 simian adenovirus isolates showed greater than 96% homology to AAV1 and AAV6 but had distinct biological properties. Two representatives of this group, AAV(VR-195) and AAV(VR-355), were studied in more detail. While the novel AAVs had high sequence homologies and required sialic acid for cell binding and transduction, differences were observed in lectin competition, resulting in distinct tropisms in human cancer cell lines.",,"['Schmidt, Michael', 'Grot, Emmanuelle', 'Cervenka, Peter', 'Wainer, Sandra', 'Buck, Charles', 'Chiorini, John A.']",,,,
,PMC,Double-Stranded RNA Is Produced by Positive-Strand RNA Viruses and DNA Viruses but Not in Detectable Amounts by Negative-Strand RNA Viruses,http://dx.doi.org/10.1128/JVI.80.10.5059-5064.2006,PMC1472073,,,"Double-stranded RNA (dsRNA) longer than 30 bp is a key activator of the innate immune response against viral infections. It is widely assumed that the generation of dsRNA during genome replication is a trait shared by all viruses. However, to our knowledge, no study exists in which the production of dsRNA by different viruses is systematically investigated. Here, we investigated the presence and localization of dsRNA in cells infected with a range of viruses, employing a dsRNA-specific antibody for immunofluorescence analysis. Our data revealed that, as predicted, significant amounts of dsRNA can be detected for viruses with a genome consisting of positive-strand RNA, dsRNA, or DNA. Surprisingly, however, no dsRNA signals were detected for negative-strand RNA viruses. Thus, dsRNA is indeed a general feature of most virus groups, but negative-strand RNA viruses appear to be an exception to that rule.",,"['Weber, Friedemann', 'Wagner, Valentina', 'Rasmussen, Simon B.', 'Hartmann, Rune', 'Paludan, Søren R.']",,,,
,PMC,Receptor-Independent Infection of Murine Coronavirus: Analysis by Spinoculation,http://dx.doi.org/10.1128/JVI.80.10.4901-4908.2006,PMC1472070,,,"A highly neurovirulent murine coronavirus JHMV (wild-type [wt] JHMV) is known to spread from cells infected via the murine coronavirus mouse hepatitis virus receptor (MHVR) to cells without MHVR (MHVR-independent infection), whereas a mutant virus isolated from wt JHMV, srr7, spread only in an MHVR-dependent fashion. These observations were obtained by the overlay of JHMV-infected cells onto receptor-negative cells that are otherwise resistant to wt JHMV infection. MHVR-independent infection is hypothetically thought to be attributed to a naturally occurring fusion activation of the wt JHMV S protein, which did not occur in the case of srr7. Attachment of S protein on cells without MHVR during the S-protein activation process seems to be a key condition. Thus, in the present study, we tried to see whether wt JHMV virions that are attached on MHVR-negative cells are able to infect those cells. In order to make virions attach to the cell surface without MHVR, we have used spinoculation, namely, the centrifugation of cells together with inoculated virus at 3,000 rpm for 2 h. This procedure forces viruses to attach to the cell surface, as revealed by quantitative estimation of attached virions by real-time PCR and also facilitated wt JHMV infection to MHVR-negative cells, but failed to do so for srr7. Virions of both wt and srr7 attached on MHVR-negative cells by spinoculation were facilitated for infection in the presence of a soluble form of MHVR that induces conformational changes of both wt and srr7. It was further revealed that wt JHMV S1, but not srr7, was released from the cell surface when S protein was expressed on cells. These observations support the hypothesis that attachment of the virion to MHVR-negative cells is a critical step and that a unique feature of wt JHMV S1 to be released from S2 in a naturally occurring event is involved in an MHVR-independent infection.",,"['Watanabe, Rie', 'Matsuyama, Shutoku', 'Taguchi, Fumihiro']",,,,
,PMC,X-Ray Crystallographic Structure of the Norwalk Virus Protease at 1.5-Å Resolution,http://dx.doi.org/10.1128/JVI.80.10.5050-5058.2006,PMC1472067,,,"Norwalk virus (NV), a member of the Caliciviridae family, is the major cause of acute, epidemic, viral gastroenteritis. The NV genome is a positive sense, single-stranded RNA that encodes three open reading frames (ORFs). The first ORF produces a polyprotein that is processed by the viral cysteine protease into six nonstructural proteins. We have determined the structure of the NV protease to 1.5 and 2.2 Å from crystals grown in the absence or presence, respectively, of the protease inhibitor AEBSF [4-(2-aminoethyl)-benzenesulfonyl fluoride]. The protease, which crystallizes as a stable dimer, exhibits a two-domain structure similar to those of other viral cysteine proteases with a catalytic triad composed of His 30, Glu 54, and Cys 139. The native structure of the protease reveals strong hydrogen bond interactions between His 30 and Glu 54, in the favorable syn configuration, indicating a role of Glu 54 during proteolysis. Mutation of this residue to Ala abolished the protease activity, in a fluorogenic peptide substrate assay, further substantiating the role of Glu 54 during proteolysis. These observations contrast with the suggestion, from a previous study of another norovirus protease, that this residue may not have a prominent role in proteolysis (K. Nakamura, Y. Someya, T. Kumasaka, G. Ueno, M. Yamamoto, T. Sato, N. Takeda, T. Miyamura, and N. Tanaka, J. Virol. 79:13685-13693, 2005). In the structure from crystals grown in the presence of AEBSF, Glu 54 undergoes a conformational change leading to disruption of the hydrogen bond interactions with His 30. Since AEBSF was not apparent in the electron density map, it is possible that these conformational changes are due to subtle changes in pH caused by its addition during crystallization.",,"['Zeitler, Corinne E.', 'Estes, Mary K.', 'Venkataram Prasad, B. V.']",,,,
,PMC,Animal Origins of the Severe Acute Respiratory Syndrome Coronavirus: Insight from ACE2-S-Protein Interactions,http://dx.doi.org/10.1128/JVI.80.9.4211-4219.2006,PMC1472041,,,,,"['Li, Wenhui', 'Wong, Swee-Kee', 'Li, Fang', 'Kuhn, Jens H.', 'Huang, I-Chueh', 'Choe, Hyeryun', 'Farzan, Michael']",,,,
,PMC,Recombinant Vesicular Stomatitis Virus Vectors Expressing Herpes Simplex Virus Type 2 gD Elicit Robust CD4(+) Th1 Immune Responses and Are Protective in Mouse and Guinea Pig Models of Vaginal Challenge,http://dx.doi.org/10.1128/JVI.80.9.4447-4457.2006,PMC1472036,,,"Recombinant vesicular stomatitis virus (rVSV) vectors offer an attractive approach for the induction of robust cellular and humoral immune responses directed against human pathogen target antigens. We evaluated rVSV vectors expressing full-length glycoprotein D (gD) from herpes simplex virus type 2 (HSV-2) in mice and guinea pigs for immunogenicity and protective efficacy against genital challenge with wild-type HSV-2. Robust Th1-polarized anti-gD immune responses were demonstrated in the murine model as measured by induction of gD-specific cytotoxic T lymphocytes and increased gamma interferon expression. The isotype makeup of the serum anti-gD immunoglobulin G (IgG) response was consistent with the presence of a Th1-CD4(+) anti-gD response, characterized by a high IgG2a/IgG1 IgG subclass ratio. Functional anti-HSV-2 neutralizing serum antibody responses were readily demonstrated in both guinea pigs and mice that had been immunized with rVSV-gD vaccines. Furthermore, guinea pigs and mice were prophylactically protected from genital challenge with high doses of wild-type HSV-2. In addition, guinea pigs were highly protected against the establishment of latent infection as evidenced by low or absent HSV-2 genome copies in dorsal root ganglia after virus challenge. In summary, rVSV-gD vectors were successfully used to elicit potent anti-gD Th1-like cellular and humoral immune responses that were protective against HSV-2 disease in guinea pigs and mice.",,"['Natuk, Robert J.', 'Cooper, David', 'Guo, Min', 'Calderon, Priscilla', 'Wright, Kevin J.', 'Nasar, Farooq', 'Witko, Susan', 'Pawlyk, Diane', 'Lee, Margaret', 'DeStefano, Joanne', 'Tummolo, Donna', 'Abramovitz, Aaron S.', 'Gangolli, Seema', 'Kalyan, Narender', 'Clarke, David K.', 'Hendry, R. Michael', 'Eldridge, John H.', 'Udem, Stephen A.', 'Kowalski, Jacek']",,,,
,PMC,Identification of Functionally Important Negatively Charged Residues in the Carboxy End of Mouse Hepatitis Coronavirus A59 Nucleocapsid Protein,http://dx.doi.org/10.1128/JVI.80.9.4344-4355.2006,PMC1472032,,,"The coronavirus nucleocapsid (N) protein is a multifunctional viral gene product that encapsidates the RNA genome and also plays some as yet not fully defined role in viral RNA replication and/or transcription. A number of conserved negatively charged amino acids are located within domain III in the carboxy end of all coronavirus N proteins. Previous studies suggested that the negatively charged residues are involved in virus assembly by mediating interaction between the membrane (M) protein carboxy tail and nucleocapsids. To determine the importance of these negatively charged residues, a series of alanine and other charged-residue substitutions were introduced in place of those in the N gene within a mouse hepatitis coronavirus A59 infectious clone. Aspartic acid residues 440 and 441 were identified as functionally important. Viruses could not be isolated when both residues were replaced by positively charged amino acids. When either amino acid was replaced by a positively charged residue or both were changed to alanine, viruses were recovered that contained second-site changes within N, but not in the M or envelope protein. The compensatory role of the new changes was confirmed by the construction of new viruses. A few viruses were recovered that retained the D(441)-to-arginine change and no compensatory changes. These viruses exhibited a small-plaque phenotype and produced significantly less virus. Overall, results from our analysis of a large panel of plaque-purified recovered viruses indicate that the negatively charged residues at positions 440 and 441 are key residues that appear to be involved in virus assembly.",,"['Verma, Sandhya', 'Bednar, Valerie', 'Blount, Andrew', 'Hogue, Brenda G.']",,,,
,PMC,An Evaluation of Web-Based Case Studies in Microscopy,,PMC3633140,,,"It is often difficult to provide students in introductory science courses with opportunities that mimic the investigative learning experience of doing research. This is particularly true in microbiology courses where advanced microscopy techniques are expensive and difficult to do. To that end, we developed three computer-based case studies around real-life scenarios. Our goals were to: (i) improve students’ understanding of advanced microscopic techniques, (ii) give students practice analyzing and interpreting data, and (iii) model a scientific approach to how these techniques are applied to current issues in microbiology. Each case requires students to use references and interpret actual microscopic images, thus giving them a more realistic experience than we could previously provide. We analyzed student learning and perceptions to these case studies. After doing the case studies, students were more able to apply microscopic methods to a realistic problem, thus demonstrating an understanding of how the methods are used. Students appreciated the intellectual challenges presented by having to interpret and analyze actual microscopic images. This approach has allowed us to introduce new areas of content to our course and to stimulate critical thinking skills, a difficult task in a large introductory microbiology course.",,"['MERKEL, SUSAN M.', 'DISPENSA, MARILYN', 'GHIORSE, WILLIAM C.']",,,,
,PMC,Are virtual communities good for our health?: They seem to be good at managing chaotic information—and may have other virtues too,,PMC1444813,,,,,"['Jadad, Alejandro R', 'Enkin, Murray W', 'Glouberman, Sholom', 'Groff, Philip', 'Stern, Anita']",,,,
,PMC,Avian influenza H5N1 in viverrids: implications for wildlife health and conservation,http://dx.doi.org/10.1098/rspb.2006.3549,PMC1634780,,,"The Asian countries chronically infected with avian influenza A H5N1 are ‘global hotspots’ for biodiversity conservation in terms of species diversity, endemism and levels of threat. Since 2003, avian influenza A H5N1 viruses have naturally infected and killed a range of wild bird species, four felid species and a mustelid. Here, we report fatal disseminated H5N1 infection in a globally threatened viverrid, the Owston's civet, in Vietnam, highlighting the risk that avian influenza H5N1 poses to mammalian and avian biodiversity across its expanding geographic range.",,"['Roberton, S.I', 'Bell, D.J', 'Smith, G.J.D', 'Nicholls, J.M', 'Chan, K.H', 'Nguyen, D.T', 'Tran, P.Q', 'Streicher, U', 'Poon, L.L.M', 'Chen, H', 'Horby, P', 'Guardo, M', 'Guan, Y', 'Peiris, J.S.M']",,,,
,PMC,Inhibition of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infectivity by peptides analogous to the viral spike protein,http://dx.doi.org/10.1016/j.virusres.2006.03.001,PMC2582734,,,"Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is the cause of an atypical pneumonia that affected Asia, North America and Europe in 2002–2003. The viral spike (S) glycoprotein is responsible for mediating receptor binding and membrane fusion. Recent studies have proposed that the carboxyl terminal portion (S2 subunit) of the S protein is a class I viral fusion protein. The Wimley and White interfacial hydrophobicity scale was used to identify regions within the CoV S2 subunit that may preferentially associate with lipid membranes with the premise that peptides analogous to these regions may function as inhibitors of viral infectivity. Five regions of high interfacial hydrophobicity spanning the length of the S2 subunit of SARS-CoV and murine hepatitis virus (MHV) were identified. Peptides analogous to regions of the N-terminus or the pre-transmembrane domain of the S2 subunit inhibited SARS-CoV plaque formation by 40–70% at concentrations of 15–30 μM. Interestingly, peptides analogous to the SARS-CoV or MHV loop region inhibited viral plaque formation by >80% at similar concentrations. The observed effects were dose-dependent (IC50 values of 2–4 μM) and not a result of peptide-mediated cell cytotoxicity. The antiviral activity of the CoV peptides tested provides an attractive basis for the development of new fusion peptide inhibitors corresponding to regions outside the fusion protein heptad repeat regions.",,"['Sainz, Bruno', 'Mossel, Eric C.', 'Gallaher, William R.', 'Wimley, William C.', 'Peters, C.J.', 'Wilson, Russell B.', 'Garry, Robert F.']",,,,
,PMC,Bird flu: Pandemic flu is not just about probability,,PMC1440654,,,,,"MacIntyre, C Raina",,,,
,PMC,Bird flu: Pandemic flu preparation: an unheeded lesson from SARS,,PMC1440626,,,,,"Lim, Meng-Kin",,,,
,PMC,Twenty-first century plague  The story of SARS,,PMC1421373,,,,,"Hughes, James M.",,,,
,PMC,Kupffer Cell-Dependent Hepatitis Occurs during Influenza Infection,http://dx.doi.org/10.2353/ajpath.2006.050875,PMC1606556,,,"Respiratory infections, including influenza in humans, are often accompanied by a hepatitis that is usually mild and self-limiting. The mechanism of this kind of liver damage is not well understood. In the present study, we show that influenza-associated hepatitis occurs due to the formation of inflammatory foci that include apoptotic hepatocytes, antigen-specific CD8(+) T cells, and Kupffer cells. Serum aminotransaminase levels were elevated, and both the histological and serum enzyme markers of hepatitis were increased in secondary influenza infection, consistent with a primary role for antigen-specific T cells in the pathogenesis. No virus could be detected in the liver, making this a pure example of “collateral damage” of the liver. Notably, removal of the Kupffer cells prevented the hepatitis. Such hepatic collateral damage may be a general consequence of expanding CD8(+) T-cell populations during many extrahepatic viral infections, yielding important implications for liver pathobiology.",,"['Polakos, Noelle K.', 'Cornejo, Judith C.', 'Murray, Debbie A.', 'Wright, Kate O.', 'Treanor, John J.', 'Crispe, I. Nicholas', 'Topham, David J.', 'Pierce, Robert H.']",,,,
,PMC,Systemic Viral Infections and Collateral Damage in the Liver,http://dx.doi.org/10.2353/ajpath.2006.051296,PMC1606546,,,,,"['Adams, David H.', 'Hubscher, Stefan G.']",,,,
,PMC,Phosphorothioate Oligonucleotides Inhibit Human Immunodeficiency Virus Type 1 Fusion by Blocking gp41 Core Formation,http://dx.doi.org/10.1128/AAC.50.4.1393-1401.2006,PMC1426958,,,"Several studies have shown that phosphorothioate oligodeoxynucleotides (PS-ONs) have a sequence-independent antiviral activity against human immunodeficiency virus type 1 (HIV-1). It has also been suggested that PS-ONs inhibit HIV-1 by acting as attachment inhibitors that bind to the V3 loop of gp120 and prevent the gp120-CD4 interaction. Here we show that PS-ONs (and their fully 2′-O-methylated derivatives) are potent inhibitors of HIV-1-mediated membrane fusion and HIV-1 replication in a size-dependent, phosphorothioation-dependent manner. PS-ONs interact with a peptide derived from the N-terminal heptad repeat region of gp41, and the HIV-1 fusion-inhibitory activity of PS-ONs is closely correlated with their ability to block gp41 six-helix bundle formation, a critical step during the process of HIV-1 fusion with the target cell. These results suggest that the increased hydrophobicity of PS-ONs may contribute to their inhibitory activity against HIV-1 fusion and entry, because longer PS-ONs (≥30 bases) which have a greater hydrophobicity are more potent in blocking the hydrophobic interactions involved in the gp41 six-helix bundle formation and inhibiting the HIV-1-mediated cell-cell fusion than shorter PS-ONs (<30 bases). This novel antiviral mechanism of action of long PS-ONs has implications for therapy against infection by HIV-1 and other enveloped viruses with type I fusion proteins.",,"['Vaillant, Andrew', 'Juteau, Jean-Marc', 'Lu, Hong', 'Liu, Shuwen', 'Lackman-Smith, Carol', 'Ptak, Roger', 'Jiang, Shibo']",,,,
,PMC,Triaryl Pyrazoline Compound Inhibits Flavivirus RNA Replication,http://dx.doi.org/10.1128/AAC.50.4.1320-1329.2006,PMC1426921,,,"Triaryl pyrazoline {[5-(4-chloro-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1-yl]-phenyl-methanone} inhibits flavivirus infection in cell culture. The inhibitor was identified through high-throughput screening of a compound library using a luciferase-expressing West Nile (WN) virus infection assay. The compound inhibited an epidemic strain of WN virus without detectable cytotoxicity (a 50% effective concentration of 28 μM and a compound concentration of ≥300 μM required to reduce 50% cell viability). Besides WN virus, the compound also inhibited other flaviviruses (dengue, yellow fever, and St. Louis encephalitis viruses), an alphavirus (Western equine encephalitis virus), a coronavirus (mouse hepatitis virus), and a rhabdovirus (vesicular stomatitis virus). However, the compound did not suppress an orthomyxovirus (influenza virus) or a retrovirus (human immunodeficiency virus type 1). Mode-of-action analyses in WN virus showed that the compound did not inhibit viral entry or virion assembly but specifically suppressed viral RNA synthesis. To examine the mechanism of inhibition of dengue virus, we developed two replicon systems for dengue type 1 virus: (i) a stable cell line that harbored replicons containing a luciferase reporter and a neomycin phosphotransferase selection marker and (ii) a luciferase-expressing replicon that could differentiate between viral translation and RNA replication. Analyses of the compound in the dengue type 1 virus replicon systems showed that it weakly suppressed viral translation but significantly inhibited viral RNA synthesis. Overall, the results demonstrate that triaryl pyrazoline exerts a broad spectrum of antiflavivirus activity through potent inhibition of viral RNA replication. This novel inhibitor could be developed for potential treatment of flavivirus infection.",,"['Puig-Basagoiti, Francesc', 'Tilgner, Mark', 'Forshey, Brett M.', 'Philpott, Sean M.', 'Espina, Noel G.', 'Wentworth, David E.', 'Goebel, Scott J.', 'Masters, Paul S.', 'Falgout, Barry', 'Ren, Ping', 'Ferguson, David M.', 'Shi, Pei-Yong']",,,,
,PMC,Hard decisions will have to be made: view from intensive care,,PMC1420713,,,,,"Marsh, Richard",,,,
,PMC,Using lessons from the past to plan for pandemic flu,,PMC1420702,,,,,"Pickles, Hilary",,,,
,PMC,,,PMC2080411,,,,,,,,,
,PMC,Current Strategies and Future Directions for Eluding Adenoviral Vector Immunity,,PMC1455550,,,"Adenoviral (Ad) vectors can efficiently transduce a broad range of cell types and have been used extensively in preclinical and clinical studies for gene delivery applications. The presence of preexisting Ad immunity in the majority of human population and a rapid development of immune response against the Ad vector backbone following the first inoculation with the vector have impeded clinical use of these vectors. In addition, a number of animal inoculation studies have demonstrated that high systemic doses of Ad vectors invariably lead to initiation of acute inflammatory responses. This is mainly due to activation of innate immunity by vector particles. In general, vector and innate immune responses drastically limit the vector transduction efficiency and the duration of transgene expression. In order to have a predictable response with Ad vectors for gene therapy applications, the above limitations must be overcome. Strategies that are being examined to circumvent these drawbacks of Ad vectors include immunosuppression, immunomodulation, serotype switching, use of targeted Ad vectors, microencapsulation of Ad vectors, use of helper-dependent (HD) Ad vectors, and development of nonhuman Ad vectors. Here we review the current understanding of immune responses to Ad vectors, and recent advances in the strategies for immune evasion to improve the vector transduction efficiency and the duration of transgene expression. Development of novel strategies for targeting specific cell types would further boost the utility of Ad vectors by enhancing the safety, efficacy and duration of transgene expression.",,"['Bangari, Dinesh S.', 'Mittal, Suresh K.']",,,,
,PMC,Broad-spectrum respiratory tract pathogen identification using resequencing DNA microarrays,http://dx.doi.org/10.1101/gr.4337206,PMC1457032,,,"The exponential growth of pathogen nucleic acid sequences available in public domain databases has invited their direct use in pathogen detection, identification, and surveillance strategies. DNA microarray technology has offered the potential for the direct DNA sequence analysis of a broad spectrum of pathogens of interest. However, to achieve the practical attainment of this potential, numerous technical issues, especially nucleic acid amplification, probe specificity, and interpretation strategies of sequence detection, need to be addressed. In this report, we demonstrate an approach that combines the use of a custom-designed Affymetrix resequencing Respiratory Pathogen Microarray (RPM v.1) with methods for microbial nucleic acid enrichment, random nucleic acid amplification, and automated sequence similarity searching for broad-spectrum respiratory pathogen surveillance. Successful proof-of-concept experiments, utilizing clinical samples obtained from patients presenting adenovirus or influenza virus-induced febrile respiratory illness (FRI), demonstrate the ability of this approach for correct species- and strain-level identification with unambiguous statistical interpretation at clinically relevant sensitivity levels. Our results underscore the feasibility of using this approach to expedite the early surveillance of diseases, and provide new information on the incidence of multiple pathogens.",,"['Lin, Baochuan', 'Wang, Zheng', 'Vora, Gary J.', 'Thornton, Jennifer A.', 'Schnur, Joel M.', 'Thach, Dzung C.', 'Blaney, Kate M.', 'Ligler, Adam G.', 'Malanoski, Anthony P.', 'Santiago, Jose', 'Walter, Elizabeth A.', 'Agan, Brian K.', 'Metzgar, David', 'Seto, Donald', 'Daum, Luke T.', 'Kruzelock, Russell', 'Rowley, Robb K.', 'Hanson, Eric H.', 'Tibbetts, Clark', 'Stenger, David A.']",,,,
,PMC,Increasing the Global Exchange of Evidence-Based Research,http://dx.doi.org/10.1111/j.1475-6773.2006.00540.x,PMC1702514,,,,,"['Pittman, Mary A', 'Svensson, Per-Gunnar']",,,,
,PMC,Follow-Up on Diagnostic Proficiency of Laboratories Equipped To Perform Orthopoxvirus Detection and Quantification by PCR: the Second International External Quality Assurance Study,http://dx.doi.org/10.1128/JCM.44.4.1283-1287.2006,PMC1448685,,,"Two years after the first external quality assurance study on bioterrorism-relevant viruses, we have conducted a follow-up study on orthopoxvirus detection by PCR. Thirty-three laboratories (27 European, 4 Austral-Asian, and 2 American) participated. Samples contained 0 to 40,000,000 DNA copies of lyophilized monkeypox, cowpox, and vaccinia virus per ml. Laboratories achieved a >80% detection chance above 56,234 copies per ml. Global sensitivity was not significantly improved over that of the first study. Twenty-seven and 9 participants, respectively, were able to genotype and quantify virus. Four of 27 genotyping results were incorrect. Quantification accuracy was significantly better for vaccinia virus than for the other viruses. False-positive results occurred in 22 (11.8%) of all 186 tests on negative samples, but 18 of these were contributed by only five laboratories. Fifty-five percent of laboratories could appropriately detect PCR inhibition. The use of either real-time PCR or commercial diagnostic kits had significant positive influence on laboratory performance.",,"['Niedrig, Matthias', 'Meyer, Hermann', 'Panning, Marcus', 'Drosten, Christian']",,,,
,PMC,Characterization of Human Metapneumovirus Infections in Israel,http://dx.doi.org/10.1128/JCM.44.4.1484-1489.2006,PMC1448678,,,"Respiratory tract infections are a leading cause of morbidity and mortality worldwide. Even with the advancement of diagnostic tools, the causative agent of 20 to 30% of upper respiratory tract infections go undiagnosed. Recently, a newly identified human respiratory virus, human metapneumovirus (hMPV), was discovered in young children in The Netherlands. To study the prevalence of hMPV infections in Israeli children, respiratory specimens from 388 hospitalized children less than 5 years of age were evaluated for the presence of hMPV RNA, which was present in 42 (10.8%) of these samples. All hMPV-positive samples were negative for respiratory syncytial virus (RSV), influenza viruses (Flu) A and B, adenovirus, and parainfluenza viruses 1, 2, and 3. Conversely, hMPV RNA was not detected in 76 RSV-positive and 38 Flu A- or B-positive samples. Most hMPV activity was between the months February and April. Sequence analysis of 20 positive samples revealed that both of the hMPV genotypes (groups 1 and 2) have circulated in central Israel during the study period. Moreover, three of the four known hMPV subgroups (1A, 1B, and 2B) were detected among the tested samples. Seroprevalence of hMPV in 204 patients from the central part of Israel revealed that 100% of the children are hMPV seropositive by the age of 5 years old. We conclude that hMPV is a common respiratory pathogen in Israel, while mixed infections of hMPV with RSV or Flu in hospitalized children are apparently rare.",,"['Regev, Liora', 'Hindiyeh, Musa', 'Shulman, Lester M.', 'Barak, Asher', 'Levy, Virginia', 'Azar, Roberto', 'Shalev, Yael', 'Grossman, Zehava', 'Mendelson, Ella']",,,,
,PMC,Rapid Detection of Norovirus from Fecal Specimens by Real-Time Reverse Transcription-Loop-Mediated Isothermal Amplification Assay,http://dx.doi.org/10.1128/JCM.44.4.1376-1381.2006,PMC1448634,,,"In this study, we developed a one-step, single-tube genogroup-specific reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for the detection of norovirus (NoV) genomes targeting from the C terminus of the RNA-dependent RNA polymerase gene to the capsid N-terminal/shell domain region. This is the first report on the development of an RT-LAMP assay for the detection of NoV genomes. Because of the diversity of NoV genotypes, we used 9 and 13 specially designed primers containing mixed bases for genogroup I (GI) and II (GII), respectively. The RT-LAMP assay had the advantages of rapidity, simplicity, specificity, and selectively and could obtain results within 90 min, generally even within 60 min, under isothermal conditions at 62°C. The detection limits for NoV genomes were between 10(2) and 10(3) copies/tube for GI and GII with differentiation by genotype, and no cross-reactions among NoV GI and GII and other gastroenteritis viruses, such as sapovirus, human astrovirus, adenovirus type 40 and 41, and group A and C rotavirus, were found. In the evaluation tests with fecal specimens obtained from gastroenteritis outbreaks, the sensitivity and specificity of the RT-LAMP assay with regard to RT-PCR were 100 and 94% for GI and 100 and 100% for GII, respectively. These findings establish that the RT-LAMP assay is potentially useful for the rapid detection of NoV genomes from fecal specimens in outbreaks of food-borne and person-to-person-transmitted gastroenteritis.",,"['Fukuda, Shinji', 'Takao, Shinichi', 'Kuwayama, Masaru', 'Shimazu, Yukie', 'Miyazaki, Kazuo']",,,,
,PMC,Cell Cycle Perturbations Induced by Infection with the Coronavirus Infectious Bronchitis Virus and Their Effect on Virus Replication,http://dx.doi.org/10.1128/JVI.80.8.4147-4156.2006,PMC1440480,,,"In eukaryotic cells, cell growth and division occur in a stepwise, orderly fashion described by a process known as the cell cycle. The relationship between positive-strand RNA viruses and the cell cycle and the concomitant effects on virus replication are not clearly understood. We have shown that infection of asynchronously replicating and synchronized replicating cells with the avian coronavirus infectious bronchitis virus (IBV), a positive-strand RNA virus, resulted in the accumulation of infected cells in the G(2)/M phase of the cell cycle. Analysis of various cell cycle-regulatory proteins and cellular morphology indicated that there was a down-regulation of cyclins D1 and D2 (G(1) regulatory cyclins) and that a proportion of virus-infected cells underwent aberrant cytokinesis, in which the cells underwent nuclear, but not cytoplasmic, division. We assessed the impact of the perturbations on the cell cycle for virus-infected cells and found that IBV-infected G(2)/M-phase-synchronized cells exhibited increased viral protein production when released from the block when compared to cells synchronized in the G(0) phase or asynchronously replicating cells. Our data suggested that IBV induces a G(2)/M phase arrest in infected cells to promote favorable conditions for viral replication.",,"['Dove, Brian', 'Brooks, Gavin', 'Bicknell, Katrina', 'Wurm, Torsten', 'Hiscox, Julian A.']",,,,
,PMC,"Stable Association of Herpes Simplex Virus with Target Membranes Is Triggered by Low pH in the Presence of the gD Receptor, HVEM",http://dx.doi.org/10.1128/JVI.80.8.3773-3780.2006,PMC1440471,,,"Using a liposome-binding assay, we investigated the requirements for activation of herpes simplex virus (HSV) into a state capable of membrane interaction. Virions were mixed with liposomes along with the ectodomain of one of three gD receptors (HVEMt, nectin-1t, or nectin-2t) and incubated under different pH and temperature conditions. Virions failed to associate with liposomes in the presence of nectin-1 or nectin-2 at any temperature or pH tested. In contrast, HVEMt triggered association of HSV with liposomes at pH 5.3 or 5.0 when incubated at 37°C, suggesting that HVEM binding and mildly acidic pH at a physiological temperature provide coactivation signals, allowing virus association with membranes. Virions incubated with HVEMt at 37°C without liposomes rapidly lost infectivity upon exposure to pH 5.0, suggesting that these conditions lead to irreversible virus inactivation in the absence of target membranes. Consistent with the idea that soluble receptor molecules provide a trigger for HSV entry, HVEMt promoted virus entry into receptor-deficient CHO K1 cells. However, in B78H1 cells, HVEMt promoted virus entry with markedly lower efficiency. Interestingly, HSV entry into receptor-bearing CHO K1 cells has been shown to proceed via a pH-dependent manner, whereas HSV entry into receptor-bearing B78H1 cells is pH independent. Based on these observations, we propose that the changes triggered by HVEM and mildly acidic pH that allow liposome association are similar or identical to changes that occur during pH-dependent HSV entry.",,"['Whitbeck, J. Charles', 'Zuo, Yi', 'Milne, Richard S. B.', 'Cohen, Gary H.', 'Eisenberg, Roselyn J.']",,,,
,PMC,Maternally Derived Recombinant Human Anti-Hantavirus Monoclonal Antibodies Are Transferred to Mouse Offspring during Lactation and Neutralize Virus In Vitro,http://dx.doi.org/10.1128/JVI.80.8.4183-4186.2006,PMC1440470,,,"Transgenic mice expressing a recombinant human monoclonal antibody (rHMAb) against hantavirus were generated. These mice could be used as models to explore the possibilities of producing rHMAbs for therapeutic purposes. The highest concentration of the rHMAb in the milk of the transgenic females was 6.6 mg/ml. The rHMAb was also detected in the sera of pups fed by the transgenic females. Both the rHMAbs in the milk of transgenic mice and those in the sera of suckling pups were found to be active against hantaviruses, although the light chain of the antibody absorbed by the pups was modified by N-linked glycosylation.",,"['Yu, Shuyang', 'Liang, Mifang', 'Fan, BaoLiang', 'Xu, Hongtao', 'Li, Chuan', 'Zhang, Quanfu', 'Li, Dexin', 'Tang, Bo', 'Li, Shijie', 'Dai, Yunping', 'Wang, Meili', 'Zheng, Min', 'Yan, Bingxue', 'Zhu, Qinghong', 'Li, Ning']",,,,
,PMC,Characterization of a Torovirus Main Proteinase,http://dx.doi.org/10.1128/JVI.80.8.4157-4167.2006,PMC1440467,,,"Viruses of the order Nidovirales encode huge replicase polyproteins. These are processed primarily by the chymotrypsin-like main proteinases (M(pro)s). So far, M(pro)s have been studied only for corona-, arteri-, and roniviruses. Here, we report the characterization of the M(pro) of toroviruses, the fourth main Nidovirus branch. Comparative sequence analysis of polyprotein 1a of equine torovirus (EToV) strain Berne, identified a serine proteinase domain, flanked by hydrophobic regions. Heterologous expression of this domain resulted in autoprocessing at flanking cleavage sites. N-terminal sequence analysis of cleavage products tentatively identified FxxQ↓(S, A) as the substrate consensus sequence. EToV M(pro) combines several traits of its closest relatives. It has a predicted three-domain structure, with two catalytic β-barrel domains and an additional C-terminal domain of unknown function. With respect to substrate specificity, the EToV M(pro) resembles its coronavirus homologue in its preference for P1-Gln, but its substrate-binding subsite, S1, more closely resembles that of arteri- and ronivirus M(pro)s, which prefer P1-Glu. Surprisingly, in contrast to the M(pro)s of corona- and roniviruses, but like that of arterivirus, the torovirus M(pro) uses serine instead of cysteine as its principal nucleophile. Under the premise that the M(pro)s of corona- and toroviruses are more closely related to each other than to those of arteri- and roniviruses, the transition from serine- to cysteine-based proteolytic catalysis (or vice versa) must have happened more than once in the course of nidovirus evolution. In this respect, it is of interest that a mutant EToV M(pro) with a Ser(165)→Cys substitution retained partial enzymatic activity.",,"['Smits, Saskia L.', 'Snijder, Eric J.', 'de Groot, Raoul J.']",,,,
,PMC,Mucosal Immunization with Surface-Displayed Severe Acute Respiratory Syndrome Coronavirus Spike Protein on Lactobacillus casei Induces Neutralizing Antibodies in Mice,http://dx.doi.org/10.1128/JVI.80.8.4079-4087.2006,PMC1440448,,,"Induction of mucosal immunity may be important for preventing SARS-CoV infections. For safe and effective delivery of viral antigens to the mucosal immune system, we have developed a novel surface antigen display system for lactic acid bacteria using the poly-γ-glutamic acid synthetase A protein (PgsA) of Bacillus subtilis as an anchoring matrix. Recombinant fusion proteins comprised of PgsA and the Spike (S) protein segments SA (residues 2 to 114) and SB (residues 264 to 596) were stably expressed in Lactobacillus casei. Surface localization of the fusion protein was verified by cellular fractionation analyses, immunofluorescence microscopy, and flow cytometry. Oral and nasal inoculations of recombinant L. casei into mice resulted in high levels of serum immunoglobulin G (IgG) and mucosal IgA, as demonstrated by enzyme-linked immunosorbent assays using S protein peptides. More importantly, these antibodies exhibited potent neutralizing activities against severe acute respiratory syndrome (SARS) pseudoviruses. Orally immunized mice mounted a greater neutralizing-antibody response than those immunized intranasally. Three new neutralizing epitopes were identified on the S protein using a peptide neutralization interference assay (residues 291 to 308, 520 to 529, and 564 to 581). These results indicate that mucosal immunization with recombinant L. casei expressing SARS-associated coronavirus S protein on its surface provides an effective means for eliciting protective immune response against the virus.",,"['Lee, Jong-Soo', 'Poo, Haryoung', 'Han, Dong P.', 'Hong, Seung-Pyo', 'Kim, Kwang', 'Cho, Michael W.', 'Kim, Eun', 'Sung, Moon-Hee', 'Kim, Chul-Joong']",,,,
,PMC,Role of Endosomal Cathepsins in Entry Mediated by the Ebola Virus Glycoprotein,http://dx.doi.org/10.1128/JVI.80.8.4174-4178.2006,PMC1440424,,,"Using chemical inhibitors and small interfering RNA (siRNA), we have confirmed roles for cathepsin B (CatB) and cathepsin L (CatL) in Ebola virus glycoprotein (GP)-mediated infection. Treatment of Ebola virus GP pseudovirions with CatB and CatL converts GP1 from a 130-kDa to a 19-kDa species. Virus with 19-kDa GP1 displays significantly enhanced infection and is largely resistant to the effects of the CatB inhibitor and siRNA, but it still requires a low-pH-dependent endosomal/lysosomal function. These and other results support a model in which CatB and CatL prime GP by generating a 19-kDa intermediate that can be acted upon by an as yet unidentified endosomal/lysosomal enzyme to trigger fusion.",,"['Schornberg, Kathryn', 'Matsuyama, Shutoku', 'Kabsch, Kirsten', 'Delos, Sue', 'Bouton, Amy', 'White, Judith']",,,,
,PMC,Protein Kinase B/Akt Is Present in Activated Form throughout the Entire Replicative Cycle of ΔU(S)3 Mutant Virus but Only at Early Times after Infection with Wild-Type Herpes Simplex Virus 1,http://dx.doi.org/10.1128/JVI.80.7.3341-3348.2006,PMC1440418,,,"The product of the herpes simplex virus 1 (HSV-1) US3 gene is a multifunctional serine-threonine protein kinase that can block apoptosis induced by proapoptotic cellular proteins, exogenous agents, or replication-defective viruses. Earlier studies showed that the U(S)3 kinase activates and functionally overlaps cellular protein kinase A (PKA). In this study we examined the status of phosphatidylinositol 3-kinase [PI(3)K] and of its effector, protein kinase B/Akt (PKB/Akt), a component of a major pathway of mammalian antiapoptotic signaling systems. We report the following. (i) Infection of target cells with HSV-1 induces transient phosphorylation of serine 473 of PKB/Akt early in infection, with a mechanism that is dependent on PI(3)K. Inhibition of PI(3)K induced apoptosis in mock-infected or ΔU(S)3 mutant-virus-infected but not in wild-type-virus-infected cells and reduced the accumulation of specific viral gene products, including the U(S)3 protein kinase, but had a marginal effect on virus yields. (ii) At later times after infection, the total amounts of PKB/Akt decreased and phosphorylated PKB/Akt forms disappeared in a U(S)3-dependent and protein phosphatase 2A-independent manner. (iii) Activation of PKA by forskolin did not mediate significant dephosphorylation of PKB/Akt. Our results are consistent with the model that PKB/Akt is activated early in infection and acts to block apoptosis in infected cells prior to the accumulation of U(S)3 protein kinase and that it persists and continues to function as an antiapoptotic protein in the absence of U(S)3 but becomes redundant or even inimical once U(S)3 protein kinase accumulates in effective amounts.",,"['Benetti, Luca', 'Roizman, Bernard']",,,,
,PMC,Functional Characterization of Heptad Repeat 1 and 2 Mutants of the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.80.7.3225-3237.2006,PMC1440416,,,"To understand the roles of heptad repeat 1(HR1) and HR2 of the spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) in virus-cell interactions, the conserved Leu or Ile residues located at positions 913, 927, 941, and 955 in HR1 and 1151, 1165, and 1179 in HR2 were individually replaced with an α-helix-breaker Pro residue. The 913P mutant was expressed mainly as a faster-migrating, lower-molecular-weight S(L) form, while the wild type and all other mutants produced similar levels of both the S(L) form and the slower-migrating, higher-molecular-weight S(H) form. The wild-type S(L) form was processed to the S(H) form, whereas the S(L) form of the 913P mutant was inefficiently converted to the S(H) form after biosynthesis. None of these mutations affected cell surface expression or binding to its cognate ACE2 receptor. In a human immunodeficiency virus type 1/SARS S coexpression study, all mutants except the 913P mutant incorporated the S(H) form into the virions as effectively as did the wild-type S(H) form. The mutation at Ile-1151 did not affect membrane fusion or viral entry. The impaired viral entry of the 927P, 941P, 955P, and 1165P mutants was due to their inability to mediate membrane fusion, whereas the defect in viral entry of the 1179P mutant occurred not at the stage of membrane fusion but rather at a postfusion stage. Our study demonstrates the functional importance of HR1 and HR2 of the SARS-CoV spike protein in membrane fusion and viral entry.",,"['Chan, Woan-Eng', 'Chuang, Chin-Kai', 'Yeh, Shiou-Hwei', 'Chang, Mau-Sun', 'Chen, Steve S.-L.']",,,,
,PMC,Mutagenesis Analysis of the nsp4 Main Proteinase Reveals Determinants of Arterivirus Replicase Polyprotein Autoprocessing,http://dx.doi.org/10.1128/JVI.80.7.3428-3437.2006,PMC1440411,,,"Nonstructural protein 4 (nsp4; 204 amino acids) is the chymotrypsin-like serine main proteinase of the arterivirus Equine arteritis virus (order Nidovirales), which controls the maturation of the replicase complex. nsp4 includes a unique C-terminal domain (CTD) connected to the catalytic two-β-barrel structure by the poorly conserved residues 155 and 156. This dipeptide might be part of a hinge region (HR) that facilitates interdomain movements and thereby regulates (in time and space) autoprocessing of replicase polyproteins pp1a and pp1ab at eight sites that are conserved in arteriviruses. To test this hypothesis, we characterized nsp4 proteinase mutants carrying either point mutations in the putative HR domain or a large deletion in the CTD. When tested in a reverse genetics system, three groups of mutants were recognized (wild-type-like, debilitated, and dead), which was in line with the expected impact of mutations on HR flexibility. When tested in a transient expression system, the effects of the mutations on the production and turnover of replicase proteins varied widely. They were cleavage product specific and revealed a pronounced modulating effect of moieties derived from the nsp1-3 region of pp1a. Mutations that were lethal affected the efficiency of polyprotein autoprocessing most strongly. These mutants may be impaired in the accumulation of nsp5-7 and/or suffer from delayed or otherwise perturbed processing at the nsp5/6 and nsp6/7 junctions. On average, the production of nsp7-8 seems to be the most resistant to debilitating nsp4 mutations. Our results further prove that the CTD is essential for a vital nsp4 property other than catalysis.",,"['van Aken, Danny', 'Snijder, Eric J.', 'Gorbalenya, Alexander E.']",,,,
,PMC,The Avian Coronavirus Infectious Bronchitis Virus Undergoes Direct Low-pH-Dependent Fusion Activation during Entry into Host Cells,http://dx.doi.org/10.1128/JVI.80.7.3180-3188.2006,PMC1440383,,,"Coronaviruses are the causative agents of respiratory disease in humans and animals, including severe acute respiratory syndrome. Fusion of coronaviruses is generally thought to occur at neutral pH, although there is also evidence for a role of acidic endosomes during entry of a variety of coronaviruses. Therefore, the molecular basis of coronavirus fusion during entry into host cells remains incompletely defined. Here, we examined coronavirus-cell fusion and entry employing the avian coronavirus infectious bronchitis virus (IBV). Virus entry into cells was inhibited by acidotropic bases and by other inhibitors of pH-dependent endocytosis. We carried out fluorescence-dequenching fusion assays of R18-labeled virions and show that for IBV, coronavirus-cell fusion occurs in a low-pH-dependent manner, with a half-maximal rate of fusion occurring at pH 5.5. Fusion was reduced, but still occurred, at lower temperatures (20°C). We observed no effect of inhibitors of endosomal proteases on the fusion event. These data are the first direct measure of virus-cell fusion for any coronavirus and demonstrate that the coronavirus IBV employs a direct, low-pH-dependent virus-cell fusion activation reaction. We further show that IBV was not inactivated, and fusion was unaffected, by prior exposure to pH 5.0 buffer. Virions also showed evidence of reversible conformational changes in their surface proteins, indicating that aspects of the fusion reaction may be reversible in nature.",,"['Chu, Victor C.', 'McElroy, Lisa J.', 'Chu, Vicky', 'Bauman, Beverley E.', 'Whittaker, Gary R.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.80.7.3127.2006,PMC1440372,,,,,,,,,
,PMC,Recovery of a Neurovirulent Human Coronavirus OC43 from an Infectious cDNA Clone,http://dx.doi.org/10.1128/JVI.80.7.3670-3674.2006,PMC1440365,,,"This study describes the assembly of a full-length cDNA clone of human coronavirus (HCoV)-OC43 in a bacterial artificial chromosome (BAC). The BAC containing the full-length infectious cDNA (pBAC-OC43(FL)) was assembled using a two-part strategy. The first step consisted in the introduction of each end of the viral genome into the BAC with accessory sequences allowing proper transcription. The second step consisted in the insertion of the whole HCoV-OC43 cDNA genome into the BAC. To produce recombinant viral particles, pBAC-OC43(FL) was transfected into BHK-21 cells. Recombinant virus displayed the same phenotypic properties as the wild-type virus, including infectious virus titers produced in cell culture and neurovirulence in mice.",,"['St-Jean, Julien R.', 'Desforges, Marc', 'Almazán, Fernando', 'Jacomy, Hélène', 'Enjuanes, Luis', 'Talbot, Pierre J.']",,,,
,PMC,Facts and ideas from anywhere,,PMC1426177,,,,,,,,,
,PMC,Rapid peptide-based screening on the substrate specificity of severe acute respiratory syndrome (SARS) coronavirus 3C-like protease by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry,http://dx.doi.org/10.1110/ps.052007306,PMC2242481,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) 3C-like protease (3CL(pro)) mediates extensive proteolytic processing of replicase polyproteins, and is considered a promising target for anti-SARS drug development. Here we present a rapid and high-throughput screening method to study the substrate specificity of SARS-CoV 3CL(pro). Six target amino acid positions flanking the SARS-CoV 3CL(pro) cleavage site were investigated. Each batch of mixed peptide substrates with defined amino acid substitutions at the target amino acid position was synthesized via the “cartridge replacement” approach and was subjected to enzymatic cleavage by recombinant SARS-CoV 3CL(pro). Susceptibility of each peptide substrate to SARS-CoV 3CL(pro) cleavage was monitored simultaneously by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The hydrophobic pocket in the P2 position at the protease cleavage site is crucial to SARS-CoV 3CL(pro)-specific binding, which is limited to substitution by hydrophobic residue. The binding interface of SARS-CoV 3CL(pro) that is facing the P1′ position is suggested to be occupied by acidic amino acids, thus the P1′ position is intolerant to acidic residue substitution, owing to electrostatic repulsion. Steric hindrance caused by some bulky or β-branching amino acids in P3 and P2′ positions may also hinder the binding of SARS-CoV 3CL(pro). This study generates a comprehensive overview of SARS-CoV 3CL(pro) substrate specificity, which serves as the design basis of synthetic peptide-based SARS-CoV 3CL(pro) inhibitors. Our experimental approach is believed to be widely applicable for investigating the substrate specificity of other proteases in a rapid and high-throughput manner that is compatible for future automated analysis.",,"['Chu, Ling-Hon Matthew', 'Choy, Wai-Yan', 'Tsai, Sau-Na', 'Rao, Zihe', 'Ngai, Sai-Ming']",,,,
,PMC,Comparative study of the effects of heptameric slippery site composition on −1 frameshifting among different eukaryotic systems,http://dx.doi.org/10.1261/rna.2225206,PMC1421095,,,"Studies of programmed −1 ribosomal frameshifting (−1 PRF) have been approached over the past two decades by many different laboratories using a diverse array of virus-derived frameshift signals in translational assay systems derived from a variety of sources. Though it is generally acknowledged that both absolute and relative −1 PRF efficiency can vary in an assay system-dependent manner, no methodical study of this phenomenon has been undertaken. To address this issue, a series of slippery site mutants of the SARS-associated coronavirus frameshift signal were systematically assayed in four different eukaryotic translational systems. HIV-1 promoted frameshifting was also compared between Escherichia coli and a human T-cell line expression systems. The results of these analyses highlight different aspects of each system, suggesting in general that (1) differences can be due to the assay systems themselves; (2) phylogenetic differences in ribosome structure can affect frameshifting efficiency; and (3) care must be taken to employ the closest phylogenetic match between a specific −1 PRF signal and the choice of translational assay system.",,"['PLANT, EWAN P.', 'DINMAN, JONATHAN D.']",,,,
,PMC,Severe acute respiratory syndrome coronavirus papain-like protease: Structure of a viral deubiquitinating enzyme,http://dx.doi.org/10.1073/pnas.0510851103,PMC1458639,,,"Replication of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) requires proteolytic processing of the replicase polyprotein by two viral cysteine proteases, a chymotrypsin-like protease (3CLpro) and a papain-like protease (PLpro). These proteases are important targets for development of antiviral drugs that would inhibit viral replication and reduce mortality associated with outbreaks of SARS-CoV. In this work, we describe the 1.85-Å crystal structure of the catalytic core of SARS-CoV PLpro and show that the overall architecture adopts a fold closely resembling that of known deubiquitinating enzymes. Key features, however, distinguish PLpro from characterized deubiquitinating enzymes, including an intact zinc-binding motif, an unobstructed catalytically competent active site, and the presence of an intriguing, ubiquitin-like N-terminal domain. To gain insight into the active-site recognition of the C-terminal tail of ubiquitin and the related LXGG motif, we propose a model of PLpro in complex with ubiquitin–aldehyde that reveals well defined sites within the catalytic cleft that help to account for strict substrate-recognition motifs.",,"['Ratia, Kiira', 'Saikatendu, Kumar Singh', 'Santarsiero, Bernard D.', 'Barretto, Naina', 'Baker, Susan C.', 'Stevens, Raymond C.', 'Mesecar, Andrew D.']",,,,
,PMC,"Biodistribution of DNA Plasmid Vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile Virus Is Similar, without Integration, despite Differing Plasmid Backbones or Gene Inserts",http://dx.doi.org/10.1093/toxsci/kfj169,PMC2377020,,,"The Vaccine Research Center has developed a number of vaccine candidates for different diseases/infectious agents (HIV-1, Severe Acute Respiratory Syndrome virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant—IL-2/Ig) based on a DNA plasmid vaccine platform. To support the clinical development of each of these vaccine candidates, preclinical studies have been performed in mice or rabbits to determine where in the body these plasmid vaccines would biodistribute and how rapidly they would clear. In the course of these studies, it has been observed that regardless of the gene insert (expressing the vaccine immunogen or cytokine adjuvant) and regardless of the promoter used to drive expression of the gene insert in the plasmid backbone, the plasmid vaccines do not biodistribute widely and remain essentially in the site of injection, in the muscle and overlying subcutis. Even though ∼ 10(14) molecules are inoculated in the studies in rabbits, by day 8 or 9(∼ 1 week postinoculation), already all but on the order of 10(4)−10(6) molecules per microgram of DNA extracted from tissue have been cleared at the injection site. Over the course of 2 months, the plasmid clears from the site of injection with only a small percentage of animals (generally 10−20%) retaining a small number of copies (generally around 100 copies) in the muscle at the injection site. This pattern of biodistribution (confined to the injection site) and clearance (within 2 months) is consistent regardless of differences in the promoter in the plasmid backbone or differences in the gene insert being expressed by the plasmid vaccine. In addition, integration has not been observed with plasmid vaccine candidates inoculated i.m. by Biojector 2000 or by needle and syringe. These data build on the repeated-dose toxicology studies performed (see companion article, Sheets et al., 2006) to demonstrate the safety and suitability for investigational human use of DNA plasmid vaccine candidates for a variety of infectious disease prevention indications.",,"['Sheets, Rebecca L.', 'Stein, Judith', 'Manetz, T. Scott', 'Duffy, Chris', 'Nason, Martha', 'Andrews, Charla', 'Kong, Wing-Pui', 'Nabel, Gary J.', 'Gomez, Phillip L.']",,,,
,PMC,"Toxicological Safety Evaluation of DNA Plasmid Vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile Virus Is Similar Despite Differing Plasmid Backbones or Gene-Inserts",http://dx.doi.org/10.1093/toxsci/kfj170,PMC2366098,,,"The Vaccine Research Center has developed a number of vaccine candidates for different diseases/infectious agents (HIV-1, Severe Acute Respiratory Syndrome virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant—IL-2/Ig) based on a DNA plasmid vaccine platform. To support the clinical development of each of these vaccine candidates, preclinical studies were performed to screen for potential toxicities (intrinsic and immunotoxicities). All treatment-related toxicities identified in these repeated-dose toxicology studies have been confined primarily to the sites of injection and seem to be the result of both the delivery method (as they are seen in both control and treated animals) and the intended immune response to the vaccine (as they occur with greater frequency and severity in treated animals). Reactogenicity at the site of injection is generally seen to be reversible as the frequency and severity diminished between doses and between the immediate and recovery termination time points. This observation also correlated with the biodistribution data reported in the companion article (Sheets et al., 2006), in which DNA plasmid vaccine was shown to remain at the site of injection, rather than biodistributing widely, and to clear over time. The results of these safety studies have been submitted to the Food and Drug Administration to support the safety of initiating clinical studies with these and related DNA plasmid vaccines. Thus far, standard repeated-dose toxicology studies have not identified any target organs for toxicity (other than the injection site) for our DNA plasmid vaccines at doses up to 8 mg per immunization, regardless of disease indication (i.e., expressed gene-insert) and despite differences (strengths) in the promoters used to drive this expression. As clinical data accumulate with these products, it will be possible to retrospectively compare the safety profiles of the products in the clinic to the results of the repeated-dose toxicology studies, in order to determine the utility of such toxicology studies for signaling potential immunotoxicities or intrinsic toxicities from DNA vaccines. These data build on the biodistribution studies performed (see companion article, Sheets et al., 2006) to demonstrate the safety and suitability for investigational human use of DNA plasmid vaccine candidates for a variety of infectious disease prevention indications.",,"['Sheets, Rebecca L.', 'Stein, Judith', 'Manetz, T. Scott', 'Andrews, Charla', 'Bailer, Robert', 'Rathmann, John', 'Gomez, Phillip L.']",,,,
,PMC,Na(+)/H(+) exchanger type 1 is a receptor for pathogenic subgroup J avian leukosis virus,http://dx.doi.org/10.1073/pnas.0509785103,PMC1459389,,,"Subgroup J avian leukosis virus (ALV-J) is a recently identified avian oncogenic retrovirus responsible for severe economic losses worldwide. In contrast with the other ALV subgroups, ALV-J predominantly induces myeloid leukosis in meat-type chickens. Despite significant homology with the other ALV subgroups across most of the genome, the envelope protein of ALV-J (EnvJ) shares low homology with the others. Pathogenicity and myeloid leukosis induction map to the env gene of ALV-J. A chimeric protein composed of the surface domain of EnvJ fused to the constant region of a rabbit IgG and mass spectrometry were used to identify the chicken Na(+)/H(+) exchanger type 1 (chNHE1) as a binding protein for ALV-J. Flow cytometry analysis and coprecipitation experiments demonstrated a specific interaction between EnvJ and chNHE1. When introduced into nonpermissive human 293T cells and quail QT6 cells, chNHE1 conferred susceptibility to EnvJ-mediated infection. Furthermore, 293T cells expressing chNHE1 fused with 293T cells expressing EnvJ in a low-pH-dependent manner. Together, these data identify chNHE1 as a cellular receptor for the highly pathogenic ALV-J.",,"['Chai, Ning', 'Bates, Paul']",,,,
,PMC,Crystallization and preliminary X-ray diffraction analysis of Nsp15 from SARS coronavirus,http://dx.doi.org/10.1107/S1744309106009407,PMC2222560,,,"The non-structural protein Nsp15 from the aetiological agent of SARS (severe acute respiratory syndrome) has recently been characterized as a uridine-specific endoribonuclease. This enzyme plays an essential role in viral replication and transcription since a mutation in the related H229E human coronavirus nsp15 gene can abolish viral RNA synthesis. SARS full-length Nsp15 (346 amino acids) has been cloned and expressed in Escherichia coli with an N-terminal hexahistidine tag and has been purified to homogeneity. The protein was subsequently crystallized using PEG 8000 or 10 000 as precipitants. Small cubic crystals of the apoenzyme were obtained from 100 nl nanodrops. They belong to space group P4(1)32 or P4(3)32, with unit-cell parameters a = b = c = 166.8 Å. Diffraction data were collected to a maximum resolution of 2.7 Å.",,"['Ricagno, Stéfano', 'Coutard, Bruno', 'Grisel, Sacha', 'Brémond, Nicolas', 'Dalle, Karen', 'Tocque, Fabienne', 'Campanacci, Valérie', 'Lichière, Julie', 'Lantez, Violaine', 'Debarnot, Claire', 'Cambillau, Christian', 'Canard, Bruno', 'Egloff, Marie-Pierre']",,,,
,PMC,"Expression, purification and crystallization of the SARS-CoV macro domain",http://dx.doi.org/10.1107/S1744309106009274,PMC2222557,,,"Macro domains or X domains are found as modules of multidomain proteins, but can also constitute a protein on their own. Recently, biochemical and structural studies of cellular macro domains have been performed, showing that they are active as ADP-ribose-1′′-phosphatases. Macro domains are also present in a number of positive-stranded RNA viruses, but their precise function in viral replication is still unknown. The major human pathogen severe acute respiratory syndrome coronavirus (SARS-CoV) encodes 16 non-structural proteins (nsps), one of which (nsp3) encompasses a macro domain. The SARS-CoV nsp3 gene region corresponding to amino acids 182–355 has been cloned, expressed in Escherichia coli, purified and crystallized. The crystals belong to space group P2(1), with unit-cell parameters a = 37.5, b = 55.6, c = 108.9 Å, β = 91.4°, and the asymmetric unit contains either two or three molecules. Both native and selenomethionine-labelled crystals diffract to 1.8 Å.",,"['Malet, Hélène', 'Dalle, Karen', 'Brémond, Nicolas', 'Tocque, Fabienne', 'Blangy, Stéphanie', 'Campanacci, Valérie', 'Coutard, Bruno', 'Grisel, Sacha', 'Lichière, Julie', 'Lantez, Violaine', 'Cambillau, Christian', 'Canard, Bruno', 'Egloff, Marie-Pierre']",,,,
,PMC,Discovery of an RNA virus 3′→5′ exoribonuclease that is critically involved in coronavirus RNA synthesis,http://dx.doi.org/10.1073/pnas.0508200103,PMC1458802,,,"Replication of the giant RNA genome of severe acute respiratory syndrome (SARS) coronavirus (CoV) and synthesis of as many as eight subgenomic (sg) mRNAs are mediated by a viral replicase-transcriptase of outstanding complexity that includes an essential endoribonuclease activity. Here, we show that the CoV replicative machinery, unlike that of other RNA viruses, also uses an exoribonuclease (ExoN) activity, which is associated with nonstructural protein (nsp) 14. Bacterially expressed forms of SARS-CoV nsp14 were shown to act on both ssRNAs and dsRNAs in a 3′→5′ direction. The activity depended on residues that are conserved in the DEDD exonuclease superfamily. The protein did not hydrolyze DNA or ribose-2′-O-methylated RNA substrates and required divalent metal ions for activity. A range of 5′-labeled ssRNA substrates were processed to final products of ≈8–12 nucleotides. When part of dsRNA or in the presence of nonlabeled dsRNA, the 5′-labeled RNA substrates were processed to significantly smaller products, indicating that binding to dsRNA in cis or trans modulates the exonucleolytic activity of nsp14. Characterization of human CoV 229E ExoN active-site mutants revealed severe defects in viral RNA synthesis, and no viable virus could be recovered. Besides strongly reduced genome replication, specific defects in sg RNA synthesis, such as aberrant sizes of specific sg RNAs and changes in the molar ratios between individual sg RNA species, were observed. Taken together, the study identifies an RNA virus ExoN activity that is involved in the synthesis of multiple RNAs from the exceptionally large genomic RNA templates of CoVs.",,"['Minskaia, Ekaterina', 'Hertzig, Tobias', 'Gorbalenya, Alexander E.', 'Campanacci, Valérie', 'Cambillau, Christian', 'Canard, Bruno', 'Ziebuhr, John']",,,,
,PMC,Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation,http://dx.doi.org/10.1073/pnas.0509961103,PMC1458783,,,"RNA viruses are notorious for their genetic plasticity and propensity to exploit new host-range opportunities, which can lead to the emergence of human disease epidemics such as severe acute respiratory syndrome, AIDS, dengue, and influenza. However, the mechanisms of host-range change involved in most of these viral emergences, particularly the genetic mechanisms of adaptation to new hosts, remain poorly understood. We studied the emergence of Venezuelan equine encephalitis virus (VEEV), an alphavirus pathogen of people and equines that has had severe health and economic effects in the Americas since the early 20th century. Between epidemics, VEE disappears for periods up to decades, and the viral source of outbreaks has remained enigmatic. Combined with phylogenetic analyses to predict mutations associated with a 1992–1993 epidemic, we used reverse genetic studies to identify an envelope glycoprotein gene mutation that mediated emergence. This mutation allowed an enzootic, equine-avirulent VEEV strain, which circulates among rodents in nearby forests to adapt for equine amplification. RNA viruses including alphaviruses exhibit high mutation frequencies. Therefore, ecological and epidemiological factors probably constrain the frequency of VEE epidemics more than the generation, via mutation, of amplification-competent (high equine viremia) virus strains. These results underscore the ability of RNA viruses to alter their host range, virulence, and epidemic potential via minor genetic changes. VEE also demonstrates the unpredictable risks to human health of anthropogenic changes such as the introduction of equines and humans into habitats that harbor zoonotic RNA viruses.",,"['Anishchenko, Michael', 'Bowen, Richard A.', 'Paessler, Slobodan', 'Austgen, Laura', 'Greene, Ivorlyne P.', 'Weaver, Scott C.']",,,,
,PMC,Changes in coagulation and fibrinolysis of post-SARS osteonecrosis in a Chinese population,http://dx.doi.org/10.1007/s00264-005-0067-6,PMC2532088,,,"The purpose of this study was to detect changes in coagulation and fibrinolysis of post-severe acute respiratory syndrome (SARS) Chinese patients with osteonecrosis, investigate the aetiology of post-SARS osteonecrosis (ON), and select the sensitive molecular markers for identifying the susceptible population. For this study, blood samples were collected from 88 patients with post-SARS ON and 52 healthy people. Activated partial thromboplastin time (APTT), protein C (PC), antithrombin III (AT–III), plasminogen activator inhibitor (PAI), activated protein C resistance (APC–R), plasminogen (PLG), von Willebrand’s factor(vWF), D–dimer (D–D), fibrinogen (Fib), and homocysteine (HCY) were examined by enzyme-linked immunosorbent assay (ELISA). We noted that blood agents of patients with ON changed obviously. APTT, PC, AT–III, PAI, APC–R, and PLG were significantly different between the two groups. Hypercoagulation and hypofibrinolysis were found in patients with post-SARS ON. Therefore, these examinations can be used to screen a population susceptible to ON. Measurements of APTT, PC, AT–III, PAI, APC–R, and PLG are sensitive blood tests for screening purposes.",,"['Sun, Wei', 'Li, Zi–rong', 'Shi, Zhen–cai', 'Zhang, Nian–fei', 'Zhang, Yuan–chun']",,,,
,PMC,Severe acute respiratory syndrome diagnostics using a coronavirus protein microarray,http://dx.doi.org/10.1073/pnas.0510921103,PMC1449637,,,"To monitor severe acute respiratory syndrome (SARS) infection, a coronavirus protein microarray that harbors proteins from SARS coronavirus (SARS-CoV) and five additional coronaviruses was constructed. These microarrays were used to screen ≈400 Canadian sera from the SARS outbreak, including samples from confirmed SARS-CoV cases, respiratory illness patients, and healthcare professionals. A computer algorithm that uses multiple classifiers to predict samples from SARS patients was developed and used to predict 206 sera from Chinese fever patients. The test assigned patients into two distinct groups: those with antibodies to SARS-CoV and those without. The microarray also identified patients with sera reactive against other coronavirus proteins. Our results correlated well with an indirect immunofluorescence test and demonstrated that viral infection can be monitored for many months after infection. We show that protein microarrays can serve as a rapid, sensitive, and simple tool for large-scale identification of viral-specific antibodies in sera.",,"['Zhu, Heng', 'Hu, Shaohui', 'Jona, Ghil', 'Zhu, Xiaowei', 'Kreiswirth, Nate', 'Willey, Barbara M.', 'Mazzulli, Tony', 'Liu, Guozhen', 'Song, Qifeng', 'Chen, Peng', 'Cameron, Mark', 'Tyler, Andrea', 'Wang, Jian', 'Wen, Jie', 'Chen, Weijun', 'Compton, Susan', 'Snyder, Michael']",,,,
,PMC,High expression level of soluble SARS spike protein mediated by adenovirus in HEK293 cells,http://dx.doi.org/10.3748/wjg.v12.i9.1452,PMC4124329,,,"AIM: To develop a highly efficacious method for preparation of soluble SARS S-protein using adenovirus vector to meet the requirement for S-protein investigation. METHODS: The human adenovirus vector was used to express the soluble S-protein (corresponding to 1~1190 amino acids) fused with Myc/His tag using codon-optimized gene construct in HEK239 cells. The recombinant adenovirus bearing S-protein gene was generated by ligation method. The expressed S-protein with Myc/His tag was purified from culture medium with Ni-NTA agarose beads followed by dialysis. The S-protein was detected by Western blot and its biologic activity was analyzed by binding to Vero cells. RESULTS: Under the conditions of infection dose (MOI of 50) and expression time (48 h), the high-level expression of S-protein was obtained. The expression level was determined to be approximately 75 μg/10(6) cells after purification. Purified soluble S-protein was readily detected by Western blot with anti-Myc antibody and showed the ability to bind to surface of Vero cells, demonstrating that the soluble S-protein could remain the biologic activity in the native molecule. CONCLUSION: The high-level expression of S-protein in HEK293 cells mediated by adenovirus can be achieved under the optimized expression conditions. The proteins possess the biologic activity, which lays a foundation for further investigation of S-protein biological function.",,"['Zhong, Fei', 'Zhong, Zhen-Yu', 'Liang, Shuang', 'Li, Xiu-Jin']",,,,
,PMC,Minerva,,PMC1388151,,,,,,,,,
,PMC,Pathogenic bacteria and viruses in induced sputum or pharyngeal secretions of adults with stable asthma,http://dx.doi.org/10.1136/thx.2005.056291,PMC2104650,,,"BACKGROUND: Respiratory infections are well known triggers of asthma exacerbations, but their role in stable adult asthma remains unclear. METHODS: 103 asthmatics and 30 control subjects were enrolled in the study. Sputum was induced by inhalation of 3% NaCl solution. Oropharyngeal swab specimens were obtained from the posterior wall of the oropharynx. Respiratory specimens were analysed by RT‐PCR for rhinovirus, enterovirus and respiratory syncytial virus and by PCR for adenovirus, Chlamydia pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis. RESULTS: Sputum samples from two of the 30 healthy controls (6.7%), five of 53 patients with mild asthma (9.4%), and eight of 50 with moderate asthma (16.0%) were positive for rhinovirus. Rhinovirus positive asthmatic subjects had more asthma symptoms and lower forced expiratory volume in 1 second (FEV(1)) (79% predicted) than rhinovirus negative cases (93.5% predicted; p = 0.020). Chlamydia pneumoniae PCR was positive in 11 healthy controls (36.6%), 11 mild asthmatics (20.8%), and 11 moderate asthmatics (22%), and PCR positive asthmatics had lower FEV(1)/FVC than negative cases (78.2% v 80.8%, p = 0.023). Bordetella pertussis PCR was positive in 30 cases: five healthy controls (16.7%), 15 mild asthmatics (28.3%), and 10 moderate asthmatics (20%). Bordetella pertussis positive individuals had lower FEV(1)/FVC (77.1% v 80.7%, p = 0.012) and more asthma symptoms than B pertussis negative cases. CONCLUSIONS: Rhinovirus, C pneumoniae, and B pertussis are found in the sputum or pharyngeal swab specimens of asthmatic subjects without concurrent symptoms of infection or asthma exacerbation, as well as in some healthy controls. Positivity is associated with lower lung function and more frequent asthma symptoms.",,"['Harju, T H', 'Leinonen, M', 'Nokso‐Koivisto, J', 'Korhonen, T', 'Räty, R', 'He, Q', 'Hovi, T', 'Mertsola, J', 'Bloigu, A', 'Rytilä, P', 'Saikku, P']",,,,
,PMC,Inhibition of Interferon-γ Signaling in Oligodendroglia Delays Coronavirus Clearance without Altering Demyelination,http://dx.doi.org/10.2353/ajpath.2006.050496,PMC1606538,,,"Infection of the central nervous system (CNS) by the neurotropic JHM strain of mouse hepatitis virus (JHMV) induces an acute encephalomyelitis associated with demyelination. To examine the anti-viral and/or regulatory role of interferon-γ (IFN-γ) signaling in the cell that synthesizes and maintains the myelin sheath, we analyzed JHMV pathogenesis in transgenic mice expressing a dominant-negative IFN-γ receptor on oligodendroglia. Defective IFN-γ signaling was associated with enhanced oligodendroglial tropism and delayed virus clearance. However, the CNS inflammatory cell composition and CD8(+) T-cell effector functions were similar between transgenic and wild-type mice, supporting unimpaired peripheral and CNS immune responses in transgenic mice. Surprisingly, increased viral load in oligodendroglia did not affect the extent of myelin loss, the frequency of oligodendroglial apoptosis, or CNS recruitment of macrophages. These data demonstrate that IFN-γ receptor signaling is critical for the control of JHMV replication in oligodendroglia. In addition, the absence of a correlation between increased oligodendroglial infection and the extent of demyelination suggests a complex pathobiology of myelin loss in which infection of oligodendroglia is required but not sufficient.",,"['González, John M.', 'Bergmann, Cornelia C.', 'Ramakrishna, Chandran', 'Hinton, David R.', 'Atkinson, Roscoe', 'Hoskin, Jason', 'Macklin, Wendy B.', 'Stohlman, Stephen A.']",,,,
,PMC,Public Health Systems Research: Setting a National Agenda,http://dx.doi.org/10.2105/AJPH.2004.046037,PMC1470524,,,"The Institute of Medicine has recommended that policy decisions about improvement of national public health systems be guided by sound scientific evidence. However, to date there is no national research agenda to help guide public health systems. The Centers for Disease Control and Prevention was called upon to lead a collaborative consensus-based process to define key research questions and establish a framework to create opportunities to better coordinate, leverage, and identify public health resources, which are increasingly scarce. The public health systems research agenda that emerged from this process has 14 overarching priority research themes. This national agenda should stimulate and guide research to meet the urgent need to improve the nation’s public health systems.",,"['Lenaway, Dennis', 'Halverson, Paul', 'Sotnikov, Sergey', 'Tilson, Hugh', 'Corso, Liza', 'Millington, Wayne']",,,,
,PMC,"Diarrheal Illness Detected Through Syndromic Surveillance After a Massive Power Outage: New York City, August 2003",http://dx.doi.org/10.2105/AJPH.2004.061358,PMC1470517,,,"Objectives. We investigated increases in diarrheal illness detected through syndromic surveillance after a power outage in New York City on August 14, 2003. Methods. The New York City Department of Health and Mental Hygiene uses emergency department, pharmacy, and absentee data to conduct syndromic surveillance for diarrhea. We conducted a case–control investigation among patients presenting during August 16 to 18, 2003, to emergency departments that participated in syndromic surveillance. We compared risk factors for diarrheal illness ascertained through structured telephone interviews for case patients presenting with diarrheal symptoms and control patients selected from a stratified random sample of nondiarrheal patients. Results. Increases in diarrhea were detected in all data streams. Of 758 patients selected for the investigation, 301 (40%) received the full interview. Among patients 13 years and older, consumption of meat (odds ratio [OR]=2.7, 95% confidence interval [CI]=1.2, 6.1) and seafood (OR=4.8; 95% CI=1.6, 14) between the power outage and symptom onset was associated with diarrheal illness. Conclusions. Diarrhea may have resulted from consumption of meat or seafood that spoiled after the power outage. Syndromic surveillance enabled prompt detection and systematic investigation of citywide illness that would otherwise have gone undetected.",,"['Marx, Melissa A.', 'Rodriguez, Carla V.', 'Greenko, Jane', 'Das, Debjani', 'Heffernan, Richard', 'Karpati, Adam M.', 'Mostashari, Farzad', 'Balter, Sharon', 'Layton, Marcelle', 'Weiss, Don']",,,,
,PMC,Stigmatization of Newly Emerging Infectious Diseases: AIDS and SARS,http://dx.doi.org/10.2105/AJPH.2004.054742,PMC1470501,,,"Objectives. We assessed relationships between sociodemographic characteristics and mental health status and knowledge of, being worried about, and stigmatization of 2 emerging infectious diseases: AIDS and SARS. Methods. We conducted a random-digit-dialed survey of 928 residents of the New York City metropolitan area as part of a study of the effects of the September 11, 2001, terrorist attacks. Questions added for this study concerned respondents’ knowledge of, worry about, and support of stigmatizing actions to control AIDS and SARS. Results. In general, respondents with greater personal resources (income, education, social support) and better mental health status had more knowledge, were less worried, and were less likely to stigmatize. This pattern held for both AIDS and SARS. Conclusions. Personal resources and mental health factors are likely to influence the public’s ability to learn about, rationally appraise the threat of, and minimize stigmatization of emerging infectious diseases such as AIDS and SARS.",,"['Des Jarlais, Don C.', 'Galea, Sandro', 'Tracy, Melissa', 'Tross, Susan', 'Vlahov, David']",,,,
,PMC,VP35 Knockdown Inhibits Ebola Virus Amplification and Protects against Lethal Infection in Mice,http://dx.doi.org/10.1128/AAC.50.3.984-993.2006,PMC1426423,,,"Phosphorodiamidate morpholino oligomers (PMO) are a class of uncharged single-stranded DNA analogs modified such that each subunit includes a phosphorodiamidate linkage and morpholine ring. PMO antisense agents have been reported to effectively interfere with the replication of several positive-strand RNA viruses in cell culture. The filoviruses, Marburg virus and Ebola virus (EBOV), are negative-strand RNA viruses that cause up to 90% lethality in human outbreaks. There is currently no commercially available vaccine or efficacious therapeutic for any filovirus. In this study, PMO conjugated to arginine-rich cell-penetrating peptide (P-PMO) and nonconjugated PMO were assayed for the ability to inhibit EBOV infection in cell culture and in a mouse model of lethal EBOV infection. A 22-mer P-PMO designed to base pair with the translation start site region of EBOV VP35 positive-sense RNA generated sequence-specific and time- and dose-dependent inhibition of EBOV amplification in cell culture. The same oligomer provided complete protection to mice when administered before or after an otherwise lethal infection of EBOV. A corresponding nonconjugated PMO, as well as nonconjugated truncated versions of 16 and 19 base residues, provided length-dependent protection to mice when administered prophylactically. Together, these data suggest that antisense PMO and P-PMO have the potential to control EBOV infection and are promising therapeutic candidates.",,"['Enterlein, Sven', 'Warfield, Kelly L.', 'Swenson, Dana L.', 'Stein, David A.', 'Smith, Jeffery L.', 'Gamble, C. Scott', 'Kroeker, Andrew D.', 'Iversen, Patrick L.', 'Bavari, Sina', 'Mühlberger, Elke']",,,,
,PMC,False-Positive Results in a Recombinant Severe Acute Respiratory Syndrome-Associated Coronavirus (SARS-CoV) Nucleocapsid-Based Western Blot Assay Were Rectified by the Use of Two Subunits (S1 and S2) of Spike for Detection of Antibody to SARS-CoV,http://dx.doi.org/10.1128/CVI.13.3.409-414.2006,PMC1391961,,,"To evaluate the reactivity of the recombinant proteins expressed in Escherichia coli strain BL21(DE3), a Western blot assay was performed by using a panel of 78 serum samples obtained, respectively, from convalescent-phase patients infected with severe acute respiratory syndrome-associated coronavirus (SARS-CoV) (30 samples) and from healthy donors (48 samples). As antigen for detection of SARS-CoV, the nucleocapsid protein (N) showed high sensitivity and strong reactivity with all samples from SARS-CoV patients and cross-reacted with all serum samples from healthy subjects, with either those obtained from China (10 samples) or those obtained from France (38 serum samples), giving then a significant rate of false positives. Specifically, our data indicated that the two subunits, S1 (residues 14 to 760) and S2 (residues 761 to 1190), resulted from the divided spike reacted with all samples from SARS-CoV patients and without any cross-reactivity with any of the healthy serum samples. Consequently, these data revealed the nonspecific nature of N protein in serodiagnosis of SARS-CoV compared with the S1 and S2, where the specificity is of 100%. Moreover, the reported results indicated that the use of one single protein as a detection antigen of SARS-CoV infection may lead to false-positive diagnosis. These may be rectified by using more than one protein for the serodiagnosis of SARS-CoV.",,"['Maache, Mimoun', 'Komurian-Pradel, Florence', 'Rajoharison, Alain', 'Perret, Magali', 'Berland, Jean-Luc', 'Pouzol, Stéphane', 'Bagnaud, Audrey', 'Duverger, Blandine', 'Xu, Jianguo', 'Osuna, Antonio', 'Paranhos-Baccalà, Glaucia']",,,,
,PMC,The rationale of fever surveillance to identify patients with severe acute respiratory syndrome in Taiwan,http://dx.doi.org/10.1136/emj.2005.027037,PMC2464446,,,"STUDY OBJECTIVE: To establish a predictive scoring system and to determine its effectiveness for severe acute respiratory syndrome (SARS) cases confirmed by RT‐PCR in patients with fever. METHODS: A study was conducted of 484 consecutive patients seen in the emergency department (ED) of our tertiary care center during the SARS outbreak in Taiwan. The scoring system was divided into triage and screening station stages. Data were analysed with multivariable and logistic regression analysis. RESULTS: Of 737 patients who presented to our ED for possible SARS from March to June 2003, we enrolled 484 patients with a temperature >38.0°C (>100.3°F) (age >18 years). Dyspnoea, diarrhoea, travel, close contact, hospital exposure, and household history were identified as predictive indicators in the triage stage. The triage score was the total of six items. With a one‐point cutoff value, the sensitivity and specificity were 81.8% (18/22) and 73.6% (340/462). Leukocytosis, thrombocytopenia, lymphopenia, and CXR were identified as predictive indicators in the fever screening stage. Screening station scores (the sum of 10 items) consisted of triage scores, white blood cell count, and CXR. With a three‐point cutoff value, the sensitivity and specificity were 95.5% (21/22) and 87.2% (403/462). CONCLUSIONS: Syndromic and traditional surveillance play a role in early identification of SARS in an endemic area. The SARS scoring system described is easily applicable and highly effective in screening patients during outbreaks.",,"['Wang, L‐M', 'Chen, Y‐C', 'Tung, S‐P', 'Chen, C‐Y', 'Chang, S‐C', 'Chiang, S‐C', 'Lee, C‐H']",,,,
,PMC,Dealing with the family: CD147 interactions with cyclophilins,http://dx.doi.org/10.1111/j.1365-2567.2005.02316.x,PMC1782239,,,"CD147 is a widely expressed plasma membrane protein that has been implicated in a variety of physiological and pathological activities. It is best known for its ability to function as extracellular matrix metalloproteinase inducer (hence the other name for this protein, EMMPRIN), but has also been shown to regulate lymphocyte responsiveness, monocarboxylate transporter expression and spermatogenesis. These functions reflect multiple interacting partners of CD147. Recently, interaction of CD147 with proteins of the cyclophilin family has been demonstrated and activity of CD147 as a signalling receptor to extarcellular cyclophilins A and B has been shown. Given that extracellular cyclophilins are potent chemotactic agents for various immune cells, further studies of the role of cyclophilin–CD147 interaction in inflammation followed. They demonstrated that agents targeting CD147 or cyclophilin had a significant anti-inflammatory effect in animal models of acute or chronic lung diseases and rheumatoid arthritis. Here, we review the current knowledge about interactions between CD147 and cyclophilins.",,"['Yurchenko, Vyacheslav', 'Constant, Stephanie', 'Bukrinsky, Michael']",,,,
,PMC,Mutual Enhancement of Virulence by Enterotoxigenic and Enteropathogenic Escherichia coli,http://dx.doi.org/10.1128/IAI.74.3.1505-1515.2006,PMC1418639,,,"Enterotoxigenic Escherichia coli (ETEC) and enteropathogenic E. coli (EPEC) are common causes of diarrhea in children in developing countries. Dual infections with both pathogens have been noted fairly frequently in studies of diarrhea around the world. In previous laboratory work, we noted that cholera toxin and forskolin markedly potentiated EPEC-induced ATP release from the host cell, and this potentiated release was found to be mediated by the cystic fibrosis transmembrane conductance regulator. In this study, we examined whether the ETEC heat-labile toxin (LT) or the heat-stable toxin (STa, also known as ST) potentiated EPEC-induced ATP release. We found that crude ETEC culture filtrates, as well as purified ETEC toxins, did potentiate EPEC-induced ATP release in cultured T84 cells. Coinfection of T84 cells with live ETEC plus EPEC bacteria also resulted in enhanced ATP release compared to EPEC alone. In Ussing chamber studies of chloride secretion, adenine nucleotides released from the host by EPEC also significantly enhanced the chloride secretory responses that were triggered by crude ETEC filtrates, purified STa, and the peptide hormone guanylin. In addition, adenosine and LT had additive or synergistic effects in inducing vacuole formation in T84 cells. Therefore, ETEC toxins and EPEC-induced damage to the host cell both enhance the virulence of the other type of E. coli. Our in vitro data demonstrate a molecular basis for a microbial interaction, which could result in increased severity of disease in vivo in individuals who are coinfected with ETEC and EPEC.",,"['Crane, John K.', 'Choudhari, Shilpa S.', 'Naeher, Tonniele M.', 'Duffey, Michael E.']",,,,
,PMC,Poster Abstracts,,PMC2291765,,,,,,,,,
,PMC,"Prevalence, Risk Factor Analysis, and Follow-Up of Infections Caused by Three Feline Hemoplasma Species in Cats in Switzerland",http://dx.doi.org/10.1128/JCM.44.3.961-969.2006,PMC1393118,,,"Recently, a third novel feline hemotropic Mycoplasma sp. (aka hemoplasma), “Candidatus Mycoplasma turicensis,” in a cat with hemolytic anemia has been described. This is the first study to investigate the prevalence, clinical manifestations, and risk factors for all three feline hemoplasma infections in a sample of 713 healthy and ill Swiss cats using newly designed quantitative real-time PCR assays. “Candidatus Mycoplasma haemominutum” infection was detected in 7.0% and 8.7% and Mycoplasma haemofelis was detected in 2.3% and 0.2% of healthy and ill cats, respectively. “Candidatus Mycoplasma turicensis” was only detected in six ill cats (1.1%); three of them were coinfected with “Candidatus Mycoplasma haemominutum.” The 16S rRNA gene sequence of 12 Swiss hemoplasma isolates revealed >98% similarity with previously published sequences. Hemoplasma infection was associated with male gender, outdoor access, and old age but not with retrovirus infection and was more frequent in certain areas of Switzerland. “Candidatus Mycoplasma haemominutum”-infected ill cats were more frequently diagnosed with renal insufficiency and exhibited higher renal blood parameters than uninfected ill cats. No correlation between hemoplasma load and packed cell volume was found, although several hemoplasma-infected cats, some coinfected with feline immunodeficiency virus or feline leukemia virus, showed hemolytic anemia. High M. haemofelis loads (>9 × 10(5) copies/ml blood) seem to lead to anemia in acutely infected cats but not in recovered long-term carriers. A repeated evaluation of 17 cats documented that the infection was acquired in one case by blood transfusion and that there were important differences among species regarding whether or not antibiotic administration led to the resolution of bacteremia.",,"['Willi, Barbara', 'Boretti, Felicitas S.', 'Baumgartner, Claudia', 'Tasker, Séverine', 'Wenger, Bettina', 'Cattori, Valentino', 'Meli, Marina L.', 'Reusch, Claudia E.', 'Lutz, Hans', 'Hofmann-Lehmann, Regina']",,,,
,PMC,Molecular Epidemiology of Bovine Coronavirus on the Basis of Comparative Analyses of the S Gene,http://dx.doi.org/10.1128/JCM.44.3.957-960.2006,PMC1393089,,,"Bovine coronavirus (BCoV), a group 2 member of the genus Coronavirus in the family Coronaviridae, is an important pathogen in cattle worldwide. It causes diarrhea in adult animals (winter dysentery), as well as enteric and respiratory diseases in calves. The annual occurrence of BCoV epidemics in Sweden and Denmark led to this investigation, with the aim to deepen the knowledge of BCoV epidemiology at the molecular level. A total of 43 samples from outbreaks in both countries were used for PCR amplification and direct sequencing of a 624-nucleotide fragment of the BCoV S gene. Sequence comparison and phylogenetic studies were performed. The results showed (i) identical sequences from different animals in the same herds and from paired nasal and fecal samples, suggesting a dominant virus circulating in each herd at a given time; (ii) sequence differences among four outbreaks in different years in the same herd, indicating new introduction of virus; (iii) identical sequences in four different Danish herds in samples obtained within 2 months, implying virus transmission between herds; and (iv) that at least two different virus strains were involved in the outbreaks of BCoV in Denmark during the spring of 2003. This study presents molecular data of BCoV infections that will contribute to an increased understanding of BCoV epidemiology in cattle populations.",,"['Liu, Lihong', 'Hägglund, Sara', 'Hakhverdyan, Mikhayil', 'Alenius, Stefan', 'Larsen, Lars Erik', 'Belák, Sándor']",,,,
,PMC,Multiple Viral Infections and Genomic Divergence among Noroviruses during an Outbreak of Acute Gastroenteritis,http://dx.doi.org/10.1128/JCM.44.3.790-797.2006,PMC1393082,,,"An epidemic outbreak of both norovirus (NV) and astrovirus (ASV) occurred on a research ship surveying Tokyo Bay, causing acute gastroenteritis in 26 of its 37 crew members. The presence of viral pathogens in fecal specimens was analyzed, and noroviruses were identified by reverse transcription-PCR in 18 (48.6%) of these specimens. In addition, astroviruses were identified in 14 (37.8%) of the fecal samples from the affected crew members, and multiple viral infections of both NV and ASV were observed in 6 cases. The genogrouping of the NV-positive samples was then examined by dot blot hybridization, and it was determined that all of the isolates were from genogroup II (GII). No bacterial pathogens were subsequently isolated from fecal specimens. Furthermore, a variety of NV strains were identified by sequencing and single-stranded conformational polymorphism (SSCP) analyses of PCR products from the fecal samples. One recombinant NV isolate, Minato/14, was identified as a recombinant NV strain of GII/6 and GII/1. The other NV isolates from this outbreak were classified into three NV genotypes (GII/1 [Minato/10], GII/4 [Minato/33], and GII/5 [Minato/6]). Furthermore, ASVs in positive samples were determined to belong to serotypes 1 and 2 by sequencing analysis. Our findings thus indicate that coinfections with NV and ASV, including a number of NV genotypes, persisted during an outbreak of gastroenteritis in a closed environment.",,"['Sasaki, Yukiko', 'Kai, Akemi', 'Hayashi, Yukinao', 'Shinkai, Takayuki', 'Noguchi, Yayoi', 'Hasegawa, Michiya', 'Sadamasu, Kenji', 'Mori, Kohji', 'Tabei, Yukiko', 'Nagashima, Mami', 'Morozumi, Satoshi', 'Yamamoto, Tomoko']",,,,
,PMC,Endogenous Cell Repair of Chronic Demyelination,http://dx.doi.org/10.1097/01.jnen.0000205142.08716.7e,PMC1635791,,,"In multiple sclerosis lesions, remyelination typically fails with repeated or chronic demyelinating episodes and results in neurologic disability. Acute demyelination models in rodents typically exhibit robust spontaneous remyelination that prevents appropriate evaluation of strategies for improving conditions of insufficient remyelination. In the current study, we used a mouse model of chronic demyelination induced by continuous ingestion of 0.2% cuprizone for 12 weeks. This chronic process depleted the oligodendrocyte progenitor population and impaired oligodendrocyte regeneration. Remyelination remained limited after removal of cuprizone from the diet. Fibroblast growth factor 2 (FGF2) expression was persistently increased in the corpus callosum of chronically demyelinated mice as compared with nonlesioned mice. We used FGF2(−/−)mice to determine whether removal of endogenous FGF2 promoted remyelination of chronically demyelinated areas. Wild-type and FGF2(−/−)mice exhibited similar demyelination during chronic cuprizone treatment. Importantly, in contrast to wild-type mice, the FGF2(−/−)mice spontaneously remyelinated completely during the recovery period after chronic demyelination. Increased remyelination in FGF2(−/−)mice correlated with enhanced oligodendroglial regeneration. FGF2 genotype did not alter the density of oligodendrocyte progenitor cells or proliferating cells after chronic demyelination. These findings indicate that attenuating FGF2 created a sufficiently permissive lesion environment for endogenous cells to effectively remyelinate viable axons even after chronic demyelination.",,"['Armstrong, Regina C.', 'Le, Tuan Q.', 'Flint, Nicole C.', 'Vana, Adam C.', 'Zhou, Yong-Xing']",,,,
,PMC,Modeling the Early Events of Severe Acute Respiratory Syndrome Coronavirus Infection In Vitro,http://dx.doi.org/10.1128/JVI.80.6.2684-2693.2006,PMC1395447,,,"The clinical picture of severe acute respiratory syndrome (SARS) is characterized by pulmonary inflammation and respiratory failure, resembling that of acute respiratory distress syndrome. However, the events that lead to the recruitment of leukocytes are poorly understood. To study the cellular response in the acute phase of SARS coronavirus (SARS-CoV)-host cell interaction, we investigated the induction of chemokines, adhesion molecules, and DC-SIGN (dendritic cell-specific ICAM-3-grabbing nonintegrin) by SARS-CoV. Immunohistochemistry revealed neutrophil, macrophage, and CD8 T-cell infiltration in the lung autopsy of a SARS patient who died during the acute phase of illness. Additionally, pneumocytes and macrophages in the patient's lung expressed P-selectin and DC-SIGN. In in vitro study, we showed that the A549 and THP-1 cell lines were susceptible to SARS-CoV. A549 cells produced CCL2/monocyte chemoattractant protein 1 (MCP-1) and CXCL8/interleukin-8 (IL-8) after interaction with SARS-CoV and expressed P-selectin and VCAM-1. Moreover, SARS-CoV induced THP-1 cells to express CCL2/MCP-1, CXCL8/IL-8, CCL3/MIP-1α, CXCL10/IP-10, CCL4/MIP-1β, and CCL5/RANTES, which attracted neutrophils, monocytes, and activated T cells in a chemotaxis assay. We also demonstrated that DC-SIGN was inducible in THP-1 as well as A549 cells after SARS-CoV infection. Our in vitro experiments modeling infection in humans together with the study of a lung biopsy of a patient who died during the early phase of infection demonstrated that SARS-CoV, through a dynamic interaction with lung epithelial cells and monocytic cells, creates an environment conducive for immune cell migration and accumulation that eventually leads to lung injury.",,"['Yen, Yu-Ting', 'Liao, Fang', 'Hsiao, Cheng-Hsiang', 'Kao, Chuan-Liang', 'Chen, Yee-Chun', 'Wu-Hsieh, Betty A.']",,,,
,PMC,Suppression of Viral RNA Recombination by a Host Exoribonuclease,http://dx.doi.org/10.1128/JVI.80.6.2631-2640.2006,PMC1395426,,,"RNA viruses of humans, animals, and plants evolve rapidly due to mutations and RNA recombination. A previous genome-wide screen in Saccharomyces cerevisiae, a model host, identified five host genes, including XRN1, encoding a 5′-3′ exoribonuclease, whose absence led to an ∼10- to 50-fold enhancement of RNA recombination in Tomato bushy stunt virus (E. Serviene, N. Shapka, C. P. Cheng, T. Panavas, B. Phuangrat, J. Baker, and P. D. Nagy, Proc. Natl. Acad. Sci. USA 102:10545-10550, 2005). In this study, we found abundant 5′-truncated viral RNAs in xrn1Δ mutant strains but not in the parental yeast strains, suggesting that these RNAs might serve as recombination substrates promoting RNA recombination in xrn1Δ mutant yeast. This model is supported by data showing that an enhanced level of viral recombinant accumulation occurred when two different 5′-truncated viral RNAs were expressed in the parental and xrn1Δ mutant yeast strains or electroporated into plant protoplasts. Moreover, we demonstrate that purified Xrn1p can degrade the 5′-truncated viral RNAs in vitro. Based on these findings, we propose that Xrn1p can suppress viral RNA recombination by rapidly removing the 5′-truncated RNAs, the substrates of recombination, and thus reducing the chance for recombination to occur in the parental yeast strain. In addition, we show that the 5′-truncated viral RNAs are generated by host endoribonucleases. Accordingly, overexpression of the Ngl2p endoribonuclease led to an increased accumulation of cleaved viral RNAs in vivo and in vitro. Altogether, this paper establishes that host ribonucleases and host-mediated viral RNA turnover play major roles in RNA virus recombination and evolution.",,"['Cheng, Chi-Ping', 'Serviene, Elena', 'Nagy, Peter D.']",,,,
,PMC,Heptad Repeat 2 in Herpes Simplex Virus 1 gH Interacts with Heptad Repeat 1 and Is Critical for Virus Entry and Fusion,http://dx.doi.org/10.1128/JVI.80.5.2216-2224.2006,PMC1395405,,,"Herpes simplex virus 1 (HSV-1) entry into cells and cell-cell fusion mediated by HSV-1 glycoproteins require four glycoproteins, gD, gB, gH, gL. Of these, gH is the only one that so far exhibits structural-functional features typical of viral fusion glycoproteins, i.e., a candidate fusion peptide and, downstream of it, a heptad repeat (HR) segment able to form a coiled coil, named HR-1. Here, we show that gH carries a functional HR-2 capable of physical interaction with HR-1. Specifically, mutational analysis of gH aimed at increasing or decreasing the ability of HR-2 to form a coiled coil resulted in an increase or decrease of fusion activity, respectively. HSV infection was modified accordingly. A mimetic peptide with the HR-2 sequence inhibited HSV-1 infection in a specific and dose-dependent manner. Circular dichroism spectroscopy showed that both HR-2 and HR-1 mimetic peptides adopt mainly random conformation in aqueous solution, while a decrease in peptide environmental polarity determines a conformational change, with a significant increase of the α-helical conformation content, in particular, for the HR-1 peptide. Furthermore, HR-1 and HR-2 mimetic peptides formed a stable complex, as revealed in nondenaturing electrophoresis and by circular dichroism. The mixture of HR-1 and HR-2 peptides reversed the inhibition of HSV infection exerted by the single peptides. Complex formation between HR-1 and HR-2 was independent of the presence of adjacent gH sequences and of additional glycoproteins involved in entry and fusion. Altogether, HR-2 adds to the features typical of class 1 fusion glycoproteins exhibited by HSV-1 gH.",,"['Gianni, Tatiana', 'Piccoli, Angela', 'Bertucci, Carlo', 'Campadelli-Fiume, Gabriella']",,,,
,PMC,Preferential Infection of Mature Dendritic Cells by Mouse Hepatitis Virus Strain JHM,http://dx.doi.org/10.1128/JVI.80.5.2506-2514.2006,PMC1395395,,,"Mouse hepatitis virus strain JHM (MHV-JHM) causes acute encephalitis and acute and chronic demyelinating diseases in mice. Dendritic cells (DCs) are key cells in the initiation of innate and adaptive immune responses, and infection of these cells could potentially contribute to a dysregulated immune response; consistent with this, recent results suggest that DCs are readily infected by another strain of mouse hepatitis virus, the A59 strain (MHV-A59). Herein, we show that the JHM strain also productively infected DCs. Moreover, mature DCs were at least 10 times more susceptible than immature DCs to infection with MHV-JHM. DC function was impaired after MHV-JHM infection, resulting in decreased stimulation of CD8 T cells in vitro. Preferential infection of mature DCs was not due to differential expression of the MHV-JHM receptor CEACAM-1a on mature or immature cells or to differences in apoptosis. Although we could not detect infected DCs in vivo, both CD8(+) and CD11b(+) splenic DCs were susceptible to infection with MHV-JHM directly ex vivo. This preferential infection of mature DCs may inhibit the development of an efficient immune response to the virus.",,"['Zhou, Haixia', 'Perlman, Stanley']",,,,
,PMC,Bovine Coronavirus 5′-Proximal Genomic Acceptor Hotspot for Discontinuous Transcription Is 65 Nucleotides Wide,http://dx.doi.org/10.1128/JVI.80.5.2183-2193.2006,PMC1395388,,,"Coronaviruses are positive-strand, RNA-dependent RNA polymerase-utilizing viruses that require a polymerase template switch, characterized as discontinuous transcription, to place a 5′-terminal genomic leader onto subgenomic mRNAs (sgmRNAs). The usually precise switch is thought to occur during the synthesis of negative-strand templates for sgmRNA production and to be directed by heptameric core donor sequences within the genome that match an acceptor core (UCUAAAC in the case of bovine coronavirus) near the 3′ end of the 5′-terminal genomic leader. Here it is shown that a 22-nucleotide (nt) donor sequence engineered into a packageable bovine coronavirus defective interfering (DI) RNA and made to match a sequence within the 65-nt virus genomic leader caused a template switch yielding an sgmRNA with only a 33-nt minileader. By changing the donor sequence, acceptor sites between genomic nt 33 and 97 (identical between the DI RNA and the viral genome) could be used to generate sgmRNAs detectable by Northern analysis (∼2 to 32 molecules per cell) by 24 h postinfection. Whether the switch was intramolecular only was not determined since a potentially distinguishing acceptor region in the DI RNA rapidly conformed to that in the helper virus genome through a previously described template switch known as leader switching. These results show that crossover acceptor sites for discontinuous transcription (i) need not include the UCUAAAC core and (ii) rest within a surprisingly wide 5′-proximal “hotspot.” Overlap of this hotspot with that for leader switching and with elements required for RNA replication suggests that it is part of a larger 5′-proximal multifunctional structure.",,"['Wu, Hung-Yi', 'Ozdarendeli, Aykut', 'Brian, David A.']",,,,
,PMC,Glycosylation of the Severe Acute Respiratory Syndrome Coronavirus Triple-Spanning Membrane Proteins 3a and M,http://dx.doi.org/10.1128/JVI.80.5.2326-2336.2006,PMC1395384,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) open reading frame 3a protein has recently been shown to be a structural protein. The protein is encoded by one of the so-called group-specific genes and has no sequence homology with any of the known structural or group-specific proteins of coronaviruses. It does, however, have several similarities to the coronavirus M proteins; (i) they are triple membrane spanning with the same topology, (ii) they have similar intracellular localizations (predominantly Golgi), (iii) both are viral structural proteins, and (iv) they appear to interact with the E and S proteins, as well as with each other. The M protein plays a crucial role in coronavirus assembly and is glycosylated in all coronaviruses, either by N-linked or by O-linked oligosaccharides. The conserved glycosylation of the coronavirus M proteins and the resemblance of the 3a protein to them led us to investigate the glycosylation of these two SARS-CoV membrane proteins. The proteins were expressed separately using the vaccinia virus T7 expression system, followed by metabolic labeling. Pulse-chase analysis showed that both proteins were modified, although in different ways. While the M protein acquired cotranslationally oligosaccharides that could be removed by PNGaseF, the 3a protein acquired its modifications posttranslationally, and they were not sensitive to the N-glycosidase enzyme. The SARS-CoV 3a protein, however, was demonstrated to contain sialic acids, indicating the presence of oligosaccharides. O-glycosylation of the 3a protein was indeed confirmed using an in situ O-glycosylation assay of endoplasmic reticulum-retained mutants. In addition, we showed that substitution of serine and threonine residues in the ectodomain of the 3a protein abolished the addition of the O-linked sugars. Thus, the SARS-CoV 3a protein is an O-glycosylated glycoprotein, like the group 2 coronavirus M proteins but unlike the SARS-CoV M protein, which is N glycosylated.",,"['Oostra, M.', 'de Haan, C. A. M.', 'de Groot, R. J.', 'Rottier, P. J. M.']",,,,
,PMC,Comparison of the Replication of Influenza A Viruses in Chinese Ring-Necked Pheasants and Chukar Partridges,http://dx.doi.org/10.1128/JVI.80.5.2151-2161.2006,PMC1395373,,,"We investigated the replication and transmission of avian influenza A viruses in two species thought to be intermediate hosts in the spread of influenza A viruses in live poultry markets: Chinese ring-necked pheasants and chukar partridges. All 15 hemagglutinin subtypes replicated in pheasants, and most subtypes transmitted to naïve contact pheasants, primarily via the fecal-oral route. Many viruses were shed from the gastrointestinal tract of experimentally inoculated pheasants for 14 days or longer. Virus was isolated from the cloacal swabs of one contact pheasant for an unprecedented 45 days. Chukar partridges were less susceptible to infection with avian influenza viruses. The viruses that replicated in chukar partridges were isolated for 7 days after experimental inoculation, predominantly from the respiratory tract. We detected high neutralizing antibody titers with correspondingly low levels of serum hemagglutination inhibition antibody titers in pheasants and chukar partridges when chicken red blood cells were used in serological analyses. When horse erythrocytes were used, antibody titers were comparable to those obtained by using the neutralization assay. More importantly, the results suggested that pheasants can serve as a reservoir of influenza virus. Because of their continuous asymptomatic infection and longer stay in the markets, pheasants are ideal “carriers” of influenza A viruses. Their continued presence in live markets contributes to the perpetuation and genetic interaction of influenza viruses there. On the basis of our findings, it does not make good sense to ban quail but not pheasants from the live markets.",,"['Humberd, Jennifer', 'Guan, Yi', 'Webster, Robert G.']",,,,
,PMC,Management of Patients with HIV in the Intensive Care Unit,http://dx.doi.org/10.1513/pats.200511-122JH,PMC2658678,,,"Because there are more than one million Americans with HIV, intensive care units continue to see frequent patients with HIV infection. In the era of highly active antiretroviral therapy, clinicians must be aware of drug toxicities and drug interactions. They must also recognize traditional opportunistic infections, as well as newer syndromes such as immune reconstitution syndrome, multicentric Castleman's disease, and primary pleural cell lymphoma.",,"Masur, Henry",,,,
,PMC,Using Blended Learning In Training The Public Health Workforce In Emergency Preparedness,,PMC1525268,,,,,"['Moore, Gary S', 'Perlow, Audrey', 'Judge, Christine', 'Koh, Howard']",,,,
,PMC,COPD exacerbations · 2: Aetiology,http://dx.doi.org/10.1136/thx.2005.041822,PMC2080749,,,"Exacerbations of COPD are thought to be caused by complex interactions between the host, bacteria, viruses, and environmental pollution. These factors increase the inflammatory burden in the lower airways, overwhelming the protective anti‐inflammatory defences leading to tissue damage. Frequent exacerbations are associated with increased morbidity and mortality, a faster decline in lung function, and poorer health status, so prevention or optimal treatment of exacerbations is a global priority. In order to evolve new treatment strategies there has been great interest in the aetiology and pathophysiology of exacerbations, but progress has been hindered by the heterogeneous nature of these episodes, vague definitions of an exacerbation, and poor stratification of known confounding factors when interpreting results. We review how an exacerbation should be defined, its inflammatory basis, and the importance of exacerbations on disease progression. Important aetiologies, with their potential underlying mechanisms, are discussed and the significance of each aetiology is considered.",,"['Sapey, E', 'Stockley, R A']",,,,
,PMC,Large-scale purification and crystallization of the endoribonuclease XendoU: troubleshooting with His-tagged proteins,http://dx.doi.org/10.1107/S1744309106006373,PMC2197201,,,"XendoU is the first endoribonuclease described in higher eukaryotes as being involved in the endonucleolytic processing of intron-encoded small nucleolar RNAs. It is conserved among eukaryotes and its viral homologue is essential in SARS replication and transcription. The large-scale purification and crystallization of recombinant XendoU are reported. The tendency of the recombinant enzyme to aggregate could be reversed upon the addition of chelating agents (EDTA, imidazole): aggregation is a potential drawback when purifying and crystallizing His-tagged proteins, which are widely used, especially in high-throughput structural studies. Purified monodisperse XendoU crystallized in two different space groups: trigonal P3(1)21, diffracting to low resolution, and monoclinic C2, diffracting to higher resolution.",,"['Renzi, Fabiana', 'Panetta, Gianna', 'Vallone, Beatrice', 'Brunori, Maurizio', 'Arceci, Massimo', 'Bozzoni, Irene', 'Laneve, Pietro', 'Caffarelli, Elisa']",,,,
,PMC,Pandemic flu -- communicating the risks.,,PMC2626509,,,,,"Chan, Margaret",,,,
,PMC,WHO clinical trials initiative to protect the public.,,PMC2626508,,,,,,,,,
,PMC,Recent news from WHO.,,PMC2626507,,,,,,,,,
,PMC,"Disease caused by non-tuberculous mycobacteria in a university hospital in Taiwan, 1997–2003",http://dx.doi.org/10.1017/S0950268805005698,PMC2870472,,,"From January 1997 to December 2003, all patients with non-tuberculous mycobacteria (NTM) isolation who were treated at a university hospital in Taiwan were evaluated. Among the 2650 NTM isolates, 1225 (46·2%) were from 412 patients with clinically significant diseases. The annual incidence (per 100 000 patients) of disease caused by NTM was 8·96 in 1997, 21·53 in 2002, and 16·55 in 2003. The major types of infections caused by NTM included isolated pulmonary infection and pleurisy (59·5%), skin/soft-tissue infections and osteomyelitis (13·8%), and disseminated diseases (13·3%). The two most common groups of organisms involved were rapidly growing mycobacteria (RGM) (41·4%) and Mycobacterium avium complex (MAC) (39%). The most common organism involved in isolated pulmonary infection and pleurisy was MAC (44·1%). RGM predominated in keratitis (94%), skin/soft-tissue infections and osteomyelitis (43·9%), and lymphadenitis (66·7%). This retrospective 7-year study demonstrated an increase in the incidence of NTM disease in a university hospital.",,"['DING, L.\xa0W.', 'LAI, C.\xa0C.', 'LEE, L.\xa0N.', 'HSUEH, P.\xa0R.']",,,,
,PMC,Supporters of Canada's health system express fears about new government,,PMC1371004,,,,,"Spurgeon, David",,,,
,PMC,Modelling the transmission of airborne infections in enclosed spaces,http://dx.doi.org/10.1017/S0950268806005875,PMC2870476,,,"The Wells–Riley equation for modelling airborne infection in indoor environments is incorporated into an SEIR epidemic model with a short incubation period to simulate the transmission dynamics of airborne infectious diseases in ventilated rooms. The model enables the effect of environmental factors such as the ventilation rate and the room occupancy to be examined, and allows the long-term impact of infection control measures to be assessed. A theoretical parametric study is carried out to demonstrate how changes to both the physical environment and infection control procedures may potentially limit the spread of short-incubation-period airborne infections in indoor environments such as hospitals.",,"['NOAKES, C.\xa0J.', 'BEGGS, C.\xa0B.', 'SLEIGH, P.\xa0A.', 'KERR, K.\xa0G.']",,,,
,PMC,Evaluation of measures to reduce international spread of SARS,http://dx.doi.org/10.1017/S0950268806005863,PMC2870475,,,"Mathematical models are used to quantify the effect of border control measures in reducing the international spread of SARS. Border screening is shown to play a relatively minor role in reducing disease spread. Assuming detection rates similar to those reported for arrival screening in Australia, screening can detect up to 10% (95% CI 3–23) of infected travellers, and reduce the probability of a large outbreak by up to 7% (95% CI 2–17). Rapid reductions in the time to diagnosis and effective facilities for the isolation of cases are essential to ensure that there will not be a large outbreak, and each week of delay in responding to imported infection approximately doubles the total number of cases. While the control response is being developed in a currently uninfected region, border screening can provide up to one week's additional time in which to improve methods for early isolation of cases.",,"['GLASS, K.', 'BECKER, N.\xa0G.']",,,,
,PMC,"Expression, purification and characterization of enterovirus-71 virus-like particles",http://dx.doi.org/10.3748/wjg.v12.i6.921,PMC4066158,,,"AIM: Enterovirus 71 (EV71) has been implicated as the etiological agent responsible for the recent outbreaks of hand, foot and mouth disease associated with severe neurological diseases in the Asia-Pacific region. METHODS: The assembly process was hypothesized to occur via an orchestrated proteolytic processing of the P1 precursor by the viral protease 3CD. To test this hypothesis, we constructed 3 recombinant baculoviruses: Bac-P1 expressing P1; Bac-3CD expressing 3CD; and Bac-P1-3CD co-expressing P1 and 3CD. RESULTS: Both single infection by Bac-P1-3CD and co-infection by Bac-P1 and Bac-3CD resulted in correct cleavage of P1 to yield individual proteins VP0, VP1 and VP3, while the former approach yielded higher VLP production. In the cells, the structural proteins self-assembled into clusters of virus-like particles (VLP) resembling the authentic EV71 particle aggregates. After ultracentrifugation purification, the dispersed VLPs were indistinguishable from the authentic virus in size, appearance, composition and surface epitopes, as determined by SDS-PAGE, Western blot, transmission electron microscopy and immunogold labeling. CONCLUSION: Our data, for the first time, suggest that in insect cells EV71 structural proteins adopt a processing and assembly pathway similar to poliovirus assembly. The preservation of particle morphology and composition suggest that the VLP may be a valuable vaccine candidate to prevent EV71 epidemics.",,"['Chung, Yao-Chi', 'Huang, Jen-Huang', 'Lai, Chia-Wei', 'Sheng, Heng-Chun', 'Shih, Shin-Ru', 'Ho, Mei-Shang', 'Hu, Yu-Chen']",,,,
,PMC,Minerva,,PMC1360421,,,,,,,,,
,PMC,The role of the airline transportation network in the prediction and predictability of global epidemics,http://dx.doi.org/10.1073/pnas.0510525103,PMC1413717,,,"The systematic study of large-scale networks has unveiled the ubiquitous presence of connectivity patterns characterized by large-scale heterogeneities and unbounded statistical fluctuations. These features affect dramatically the behavior of the diffusion processes occurring on networks, determining the ensuing statistical properties of their evolution pattern and dynamics. In this article, we present a stochastic computational framework for the forecast of global epidemics that considers the complete worldwide air travel infrastructure complemented with census population data. We address two basic issues in global epidemic modeling: (i) we study the role of the large scale properties of the airline transportation network in determining the global diffusion pattern of emerging diseases; and (ii) we evaluate the reliability of forecasts and outbreak scenarios with respect to the intrinsic stochasticity of disease transmission and traffic flows. To address these issues we define a set of quantitative measures able to characterize the level of heterogeneity and predictability of the epidemic pattern. These measures may be used for the analysis of containment policies and epidemic risk assessment.",,"['Colizza, Vittoria', 'Barrat, Alain', 'Barthélemy, Marc', 'Vespignani, Alessandro']",,,,
,PMC,Clinical Applications of Molecular Biology for Infectious Diseases,,PMC1390794,,,"Molecular biological methods for the detection and characterisation of microorganisms have revolutionised diagnostic microbiology and are now part of routine specimen processing. Polymerase chain reaction (PCR) techniques have led the way into this new era by allowing rapid detection of microorganisms that were previously difficult or impossible to detect by traditional microbiological methods. In addition to detection of fastidious microorganisms, more rapid detection by molecular methods is now possible for pathogens of public health importance. Molecular methods have now progressed beyond identification to detect antimicrobial resistance genes and provide public health information such as strain characterisation by genotyping. Treatment of certain microorganisms has been improved by viral resistance detection and viral load testing for the monitoring of responses to antiviral therapies. With the advent of multiplex PCR, real-time PCR and improvements in efficiency through automation, the costs of molecular methods are decreasing such that the role of molecular methods will further increase. This review will focus on the clinical utility of molecular methods performed in the clinical microbiology laboratory, illustrated with the many examples of how they have changed laboratory diagnosis and therefore the management of infectious diseases.",,"Speers, David J",,,,
,PMC,Pleiotropic Costs of Niche Expansion in the RNA Bacteriophage Φ6,http://dx.doi.org/10.1534/genetics.105.051136,PMC1456241,,,"Natural and experimental systems have failed to universally demonstrate a trade-off between generalism and specialism. When a trade-off does occur it is difficult to attribute its cause to antagonistic pleiotropy without dissecting the genetic basis of adaptation, and few previous experiments provide these genetic data. Here we investigate the evolution of expanded host range (generalism) in the RNA virus Φ6, an experimental model system allowing adaptive mutations to be readily identified. We isolated 10 spontaneous host range mutants on each of three novel Pseudomonas hosts and determined whether these mutations imposed fitness costs on the standard laboratory host. Sequencing revealed that each mutant had one of nine nonsynonymous mutations in the Φ6 gene P3, important in host attachment. Seven of these nine mutations were costly on the original host, confirming the existence of antagonistic pleiotropy. In addition to this genetically imposed cost, we identified an epigenetic cost of generalism that occurs when phage transition between host types. Our results confirm the existence in Φ6 of two costs of generalism, genetic and environmental, but they also indicate that the cost is not always large. The possibility for cost-free niche expansion implies that varied ecological conditions may favor host shifts in RNA viruses.",,"['Duffy, Siobain', 'Turner, Paul E.', 'Burch, Christina L.']",,,,
,PMC,Epidemiological and Genetic Correlates of Severe Acute Respiratory Syndrome Coronavirus Infection in the Hospital with the Highest Nosocomial Infection Rate in Taiwan in 2003,http://dx.doi.org/10.1128/JCM.44.2.359-365.2006,PMC1392693,,,"Taiwan experienced a series of outbreaks of nosocomial severe acute respiratory syndrome (SARS) infections in 2003. Two months after the final outbreak, we recruited 658 employees from the hospital that suffered the first and most severe SARS infections to help us investigate epidemiological and genetic factors associated with the SARS coronavirus (SARS-CoV). SARS-CoV infections were detected by using enzyme immunoassays and confirmed by a combination of Western blot assays, neutralizing antibody tests, and commercial SARS tests. Risk factors were analyzed via questionnaire responses and sequence-specific oligonucleotide probes of human leukocyte antigen (HLA) alleles. Our results indicate that 3% (20/658) of the study participants were seropositive, with one female nurse identified as a subclinical case. Identified SARS-CoV infection risk factors include working in the same building as the hospital's emergency room and infection ward, providing direct care to SARS patients, and carrying a Cw*0801 HLA allele. The odds ratio for contracting a SARS-CoV infection among persons with either a homozygous or a heterozygous Cw*0801 genotype was 4.4 (95% confidence interval, 1.5 to 12.9; P = 0.007).",,"['Chen, Yi-Ming Arthur', 'Liang, Shu-Yuan', 'Shih, Yi-Ping', 'Chen, Chia-Yen', 'Lee, Yuan-Ming', 'Chang, Ling', 'Jung, Shiao-Ying', 'Ho, Mei-Shang', 'Liang, Kung-Yee', 'Chen, Hour-Young', 'Chan, Yu-Jiun', 'Chu, Da-Chen']",,,,
,PMC,Neonatal Mortality in Puppies Due to Bacteremia by Streptococcus dysgalactiae subsp. dysgalactiae,http://dx.doi.org/10.1128/JCM.44.2.666-668.2006,PMC1392640,,,We report a case of bacteremia in puppies caused by Streptococcus dysgalactiae subsp. dysgalactiae. Identification was achieved by phenotypic and molecular genetic methods. This is the first report of the recovery of S. dysgalactiae subsp. dysgalactiae from dogs.,,"['Vela, Ana I.', 'Falsen, Enevold', 'Simarro, Isabel', 'Rollan, Eduardo', 'Collins, Matthew D.', 'Domínguez, Lucas', 'Fernandez-Garayzabal, Jose F.']",,,,
,PMC,Time- and Temperature-Dependent Activation of Hepatitis C Virus for Low-pH-Triggered Entry,http://dx.doi.org/10.1128/JVI.80.4.1734-1741.2006,PMC1367161,,,"Hepatitis C virus (HCV) is an important human pathogen associated with chronic liver disease. Recently, based on a genotype 2a isolate, tissue culture systems supporting complete replication and infectious virus production have been developed. In this study, we used cell culture-produced infectious HCV to analyze the viral entry pathway into Huh-7.5 cells. Bafilomycin A1 and concanamycin A, inhibitors of vacuolar ATPases, prevented HCV entry when they were present prior to infection and had minimal effect on downstream replication events. HCV entry therefore appears to be pH dependent, requiring an acidified intracellular compartment. For many other enveloped viruses, acidic pH triggers an irreversible conformational change, which promotes virion-endosomal membrane fusion. Such viruses are often inactivated by low pH. In the case of HCV, exposure of virions to acidic pH followed by return to neutral pH did not affect their infectivity. This parallels the observation made for the related pestivirus bovine viral diarrhea virus. Low pH could activate the entry of cell surface-bound HCV but only after prolonged incubation at 37°C. This suggests that there are rate-limiting, postbinding events that are needed to render HCV competent for low-pH-triggered entry. Such events may involve interaction with a cellular coreceptor or other factors but do not require cathepsins B and L, late endosomal proteases that activate Ebola virus and reovirus for entry.",,"['Tscherne, Donna M.', 'Jones, Christopher T.', 'Evans, Matthew J.', 'Lindenbach, Brett D.', 'McKeating, Jane A.', 'Rice, Charles M.']",,,,
,PMC,Site-Directed Mutagenesis of the Nidovirus Replicative Endoribonuclease NendoU Exerts Pleiotropic Effects on the Arterivirus Life Cycle,http://dx.doi.org/10.1128/JVI.80.4.1653-1661.2006,PMC1367138,,,"The highly conserved NendoU replicative domain of nidoviruses (arteriviruses, coronaviruses, and roniviruses) belongs to a small protein family whose cellular branch is prototyped by XendoU, a Xenopus laevis endoribonuclease involved in nucleolar RNA processing. Recently, sequence-specific in vitro endoribonuclease activity was demonstrated for the NendoU-containing nonstructural protein (nsp) 15 of several coronaviruses. To investigate the biological role of this novel enzymatic activity, we have characterized a comprehensive set of arterivirus NendoU mutants. Deleting parts of the NendoU domain from nsp11 of equine arteritis virus was lethal. Site-directed mutagenesis of conserved residues exerted pleiotropic effects. In a first-cycle analysis, replacement of two conserved Asp residues in the C-terminal part of NendoU rendered viral RNA synthesis and virus production undetectable. In contrast, mutagenesis of other conserved residues, including two putative catalytic His residues that are absolutely conserved in NendoU and cellular homologs, produced viable mutants displaying reduced plaque sizes (20 to 80% reduction) and reduced yields of infectious progeny of up to 5 log units. A more detailed analysis of these mutants revealed a moderate reduction in RNA synthesis, with subgenomic RNA synthesis consistently being more strongly affected than genome replication. Our data suggest that the arterivirus nsp11 is a multifunctional protein with a key role in viral RNA synthesis and additional functions in the viral life cycle that are as yet poorly defined.",,"['Posthuma, Clara C.', 'Nedialkova, Danny D.', 'Zevenhoven-Dobbe, Jessika C.', 'Blokhuis, Jeroen H.', 'Gorbalenya, Alexander E.', 'Snijder, Eric J.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.80.3.1065-1066.2006,PMC1346973,,,,,,,,,
,PMC,"JAM-A-Independent, Antibody-Mediated Uptake of Reovirus into Cells Leads to Apoptosis",http://dx.doi.org/10.1128/JVI.80.3.1261-1270.2006,PMC1346953,,,"Apoptosis plays a major role in the cytopathic effect induced by reovirus following infection of cultured cells and newborn mice. Strain-specific differences in the capacity of reovirus to induce apoptosis segregate with the S1 and M2 gene segments, which encode attachment protein σ1 and membrane penetration protein μ1, respectively. Virus strains that bind to both junctional adhesion molecule-A (JAM-A) and sialic acid are the most potent inducers of apoptosis. In addition to receptor binding, events in reovirus replication that occur during or after viral disassembly but prior to initiation of viral RNA synthesis also are required for reovirus-induced apoptosis. To determine whether reovirus infection initiated in the absence of JAM-A and sialic acid results in apoptosis, Chinese hamster ovary (CHO) cells engineered to express Fc receptors were infected with reovirus using antibodies directed against viral outer-capsid proteins. Fc-mediated infection of CHO cells induced apoptosis in a σ1-independent manner. Apoptosis following this uptake mechanism requires acid-dependent proteolytic disassembly, since treatment of cells with the weak base ammonium chloride diminished the apoptotic response. Analysis of T1L × T3D reassortant viruses revealed that the μ1-encoding M2 gene segment is the only viral determinant of the apoptosis-inducing capacity of reovirus when infection is initiated via Fc receptors. Additionally, a temperature-sensitive, membrane penetration-defective M2 mutant, tsA279.64, is an inefficient inducer of apoptosis. These data suggest that signaling pathways activated by binding of σ1 to JAM-A and sialic acid are dispensable for reovirus-mediated apoptosis and that the μ1 protein plays an essential role in stimulating proapoptotic signaling.",,"['Danthi, Pranav', 'Hansberger, Mark W.', 'Campbell, Jacquelyn A.', 'Forrest, J. Craig', 'Dermody, Terence S.']",,,,
,PMC,Redirecting Coronavirus to a Nonnative Receptor through a Virus-Encoded Targeting Adapter,http://dx.doi.org/10.1128/JVI.80.3.1250-1260.2006,PMC1346946,,,"Murine hepatitis coronavirus (MHV)-A59 infection depends on the interaction of its spike (S) protein with the cellular receptor mCEACAM1a present on murine cells. Human cells lack this receptor and are therefore not susceptible to MHV. Specific alleviation of the tropism barrier by redirecting MHV to a tumor-specific receptor could lead to a virus with appealing properties for tumor therapy. To demonstrate that MHV can be retargeted to a nonnative receptor on human cells, we produced bispecific adapter proteins composed of the N-terminal D1 domain of mCEACAM1a linked to a short targeting peptide, the six-amino-acid His tag. Preincubation of MHV with the adapter proteins and subsequent inoculation of human cells expressing an artificial His receptor resulted in infection of these otherwise nonsusceptible cells and led to subsequent production of progeny virus. To generate a self-targeted virus able to establish multiround infection of the target cells, we subsequently incorporated the gene encoding the bispecific adapter protein as an additional expression cassette into the MHV genome through targeted RNA recombination. When inoculated onto murine LR7 cells, the resulting recombinant virus indeed expressed the adapter protein. Furthermore, inoculation of human target cells with the virus resulted in a His receptor-specific infection that was multiround. Extensive cell-cell fusion and rapid cell killing of infected target cells was observed. Our results show that MHV can be genetically redirected via adapters composed of the S protein binding part of mCEACAM1a and a targeting peptide recognizing a nonnative receptor expressed on human cells, consequently leading to rapid cell death. The results provide interesting leads for further investigations of the use of coronaviruses as antitumor agents.",,"['Verheije, M. H.', 'Würdinger, T.', 'van Beusechem, V. W.', 'de Haan, C. A. M.', 'Gerritsen, W. R.', 'Rottier, P. J. M.']",,,,
,PMC,Bidirectional Virus Secretion and Nonciliated Cell Tropism following Andes Virus Infection of Primary Airway Epithelial Cell Cultures,http://dx.doi.org/10.1128/JVI.80.3.1087-1097.2006,PMC1346943,,,"Hantavirus pulmonary syndrome (HPS) is an acute disease resulting from infection with any one of a number of New World hantaviruses. HPS has a mortality rate of 40% and, unlike many other severe respiratory diseases, often occurs in young, healthy adults. Infection is usually initiated after inhalation of rodent excreta containing virus particles, but human-to-human transmission has been documented. Postmortem tissue samples show high levels of viral antigen within the respiratory endothelium, but it is not clear how the virus can traverse the respiratory epithelium in order to initiate infection in the microvasculature. We have utilized Andes virus infection of primary, differentiated airway epithelial cells to investigate the ability of the virus to interact with and cross the respiratory epithelium. Andes virus infects the Clara and goblet cell populations but not the ciliated cells, and this infection pattern corresponds to the expression of β(3) integrin, the viral receptor. The virus can infect via the apical or basolateral membrane, and progeny virus particles are secreted bidirectionally. There is no obvious cytopathology associated with infection, and β(3) integrins do not appear to be critical for respiratory epithelial cell monolayer integrity. Our data suggest that hantavirus infection of the respiratory epithelium may play an important role in the early or prodrome phase of disease as well as serving as a source of virus involved in transmission.",,"['Rowe, Regina K.', 'Pekosz, Andrew']",,,,
,PMC,Palmitoylations on Murine Coronavirus Spike Proteins Are Essential for Virion Assembly and Infectivity,http://dx.doi.org/10.1128/JVI.80.3.1280-1289.2006,PMC1346925,,,"Coronavirus spike (S) proteins are palmitoylated at several cysteine residues clustered near their transmembrane-spanning domains. This is achieved by cellular palmitoyl acyltransferases (PATs), which can modify newly synthesized S proteins before they are assembled into virion envelopes at the intermediate compartment of the exocytic pathway. To address the importance of these fatty acylations to coronavirus infection, we exposed infected cells to 2-bromopalmitate (2-BP), a specific PAT inhibitor. 2-BP profoundly reduced the specific infectivities of murine coronaviruses at very low, nontoxic doses that were inert to alphavirus and rhabdovirus infections. 2-BP effected only two- to fivefold reductions in S palmitoylation, yet this correlated with reduced S complexing with virion membrane (M) proteins and consequent exclusion of S from virions. At defined 2-BP doses, underpalmitoylated S proteins instead trafficked to infected cell surfaces and elicited cell-cell membrane fusions, suggesting that the acyl chain adducts are more critical to virion assembly than to S-induced syncytial developments. These studies involving pharmacologic inhibition of S protein palmitoylation were complemented with molecular genetic analyses in which cysteine acylation substrates were mutated. Notably, some mutations (C1347F and C1348S) did not interfere with S incorporation into virions, indicating that only a subset of the cysteine-rich region provides the essential S-assembly functions. However, the C1347F/C1348S mutant viruses exhibited relatively low specific infectivities, similar to virions secreted from 2-BP-treated cultures. Our collective results indicate that the palmitate adducts on coronavirus S proteins are necessary in assembly and also in positioning the assembled envelope proteins for maximal infectivity.",,"['Thorp, Edward B.', 'Boscarino, Joseph A.', 'Logan, Hillary L.', 'Goletz, Jeffrey T.', 'Gallagher, Thomas M.']",,,,
,PMC,Important Role for the Transmembrane Domain of Severe Acute Respiratory Syndrome Coronavirus Spike Protein during Entry,http://dx.doi.org/10.1128/JVI.80.3.1302-1310.2006,PMC1346921,,,"The spike protein (S) of severe acute respiratory syndrome coronavirus (SARS-CoV) is responsible for receptor binding and membrane fusion. It contains a highly conserved transmembrane domain that consists of three parts: an N-terminal tryptophan-rich domain, a central domain, and a cysteine-rich C-terminal domain. The cytoplasmic tail of S has previously been shown to be required for assembly. Here, the roles of the transmembrane and cytoplasmic domains of S in the infectivity and membrane fusion activity of SARS-CoV have been studied. SARS-CoV S-pseudotyped retrovirus (SARSpp) was used to measure S-mediated infectivity. In addition, the cell-cell fusion activity of S was monitored by a Renilla luciferase-based cell-cell fusion assay. Svsv-cyt, an S chimera with a cytoplasmic tail derived from vesicular stomatitis virus G protein (VSV-G), and Smhv-tmdcyt, an S chimera with the cytoplasmic and transmembrane domains of mouse hepatitis virus, displayed wild-type-like activity in both assays. Svsv-tmdcyt, a chimera with the cytoplasmic and transmembrane domains of VSV-G, was impaired in the SARSpp and cell-cell fusion assays, showing 3 to 25% activity compared to the wild type, depending on the assay and the cells used. Examination of the oligomeric state of the chimeric S proteins in SARSpp revealed that Svsv-tmdcyt trimers were less stable than wild-type S trimers, possibly explaining the lowered fusogenicity and infectivity.",,"['Broer, Rene', 'Boson, Bertrand', 'Spaan, Willy', 'Cosset, François-Loïc', 'Corver, Jeroen']",,,,
,PMC,Cardiovascular complications of severe acute respiratory syndrome,http://dx.doi.org/10.1136/pgmj.2005.037515,PMC2596695,,,"BACKGROUND AND AIMS: Severe acute respiratory syndrome (SARS) is a virulent viral infection that affects a number of organs and systems. This study examined if SARS may result in cardiovascular complications. METHODS AND RESULTS: 121 patients (37.5 (SD13.2) years, 36% male) diagnosed to have SARS were assessed continuously for blood pressure, pulse, and temperature during their stay in hopsital. Hypotension occurred in 61 (50.4%) patients in hospital, and was found in 28.1%, 21.5%, and 14.8% of patients during the first, second, and third week, respectively. Only one patient who had transient echocardiographic evidence of impaired left ventricular systolic function required temporary inotropic support. Tachycardia was present in 87 (71.9%) patients, and was found in 62.8%, 45.4%, and 35.5% of patients from the first to third week. It occurred independent of hypotension, and could not be explained by the presence of fever. Tachycardia was also present in 38.8% of patients at follow up. Bradycardia only occurred in 18 (14.9%) patients as a transient event. Reversible cardiomegaly was reported in 13 (10.7%) patients, but without clinical evidence of heart failure. Transient atrial fibrillation was present in one patient. Corticosteroid therapy was weakly associated with tachycardia during the second (χ(2) = 3.99, p = 0.046) and third week (χ(2) = 6.53, p = 0.01), although it could not explain tachycardia during follow up. CONCLUSIONS: In patients with SARS, cardiovascular complications including hypotension and tachycardia were common but usually self limiting. Bradycardia and cardiomegaly were less common, while cardiac arrhythmia was rare. However, only tachycardia persisted even when corticosteroid therapy was withdrawn.",,"['Yu, C‐M', 'Wong, R S‐M', 'Wu, E B', 'Kong, S‐L', 'Wong, J', 'Yip, G W‐K', 'Soo, Y O Y', 'Chiu, M L S', 'Chan, Y‐S', 'Hui, D', 'Lee, N', 'Wu, A', 'Leung, C‐B', 'Sung, J J‐Y']",,,,
,PMC,Longer term follow up of aerobic capacity in children affected by severe acute respiratory syndrome (SARS),http://dx.doi.org/10.1136/thx.2005.046854,PMC2080724,,,"BACKGROUND: A study was undertaken to investigate the aerobic capacity and pulmonary function of children 6 and 15 months after the diagnosis of severe acute respiratory syndrome (SARS). METHODS: Thirty four patients of mean age 14.7 years completed both pulmonary function and maximal aerobic capacity tests at 6 months. All had normal clinical examination and were asymptomatic. Their exercise responses were compared with a group of healthy controls. Complete data were collected on 27 of the original 34 cases at 15 months. RESULTS: Compared with normal controls, the patient group had significantly lower absolute and mass related peak oxygen consumption (peak V̇o(2) (p<0.01)), higher ventilatory equivalent for oxygen (p<0.01), lower oxygen pulse (p<0.01), and a lower oxygen uptake efficiency slope (p<0.01) at 6 months. This impairment was unexpected and out of proportion with the degree of lung function abnormality. Residual high resolution computed tomography of thorax (HRCT) abnormalities were present in 14 patients. Those with abnormal HRCT findings had significantly lower mass related peak V̇o(2) than subjects with normal radiology (p<0.01). Absolute and mass related peak V̇o(2) in the patient group remained impaired at 15 months despite normalisation of lung function in all patients. CONCLUSIONS: The mechanism for the reduced aerobic capacity in children following SARS is not fully understood, but it is probably a consequence of impaired perfusion to the lungs at peak exercise and deconditioning.",,"['Yu, C C W', 'Li, A M', 'So, R C H', 'McManus, A', 'Ng, P C', 'Chu, W', 'Chan, D', 'Cheng, F', 'Chiu, W K', 'Leung, C W', 'Yau, Y S', 'Mo, K W', 'Wong, E M C', 'Cheung, A Y K', 'Leung, T F', 'Sung, R Y T', 'Fok, T F']",,,,
,PMC,Global surveillance for chemical incidents of international public health concern.,,PMC2626489,,,"OBJECTIVE: In December 2001, an expert consultation convened by WHO identified strengthening national and global chemical incident preparedness and response as a priority. WHO is working towards this objective by developing a surveillance and response system for chemical incidents. This report describes the frequency, nature and geographical location of acute chemical incidents of potential international concern from August 2002 to December 2003. METHODS: Acute chemical incidents were actively identified through several informal (e.g. Internet-based resources) and formal (e.g. various networks of organizations) sources and assessed against criteria for public health emergencies of international concern using the then proposed revised International Health Regulations (IHR). WHO regional and country offices were contacted to obtain additional information regarding identified incidents. FINDINGS: Altogether, 35 chemical incidents from 26 countries met one or more of the IHR criteria. The WHO European Region accounted for 43% (15/35) of reports. The WHO Regions for Africa, Eastern Mediterranean and Western Pacific each accounted for 14% (5/35); South-East Asia and the Americas accounted for 9% (3/35) and 6% (2/35), respectively. Twenty-three (66%) events were identified within 24 hours of their occurrence. CONCLUSION: To our knowledge this is the first global surveillance system for chemical incidents of potential international concern. Limitations such as geographical and language bias associated with the current system are being addressed. Nevertheless, the system has shown that it can provide early detection of important events, as well as information on the magnitude and geographical distribution of such incidents. It can therefore contribute to improving global public health preparedness.",,"['Olowokure, B.', 'Pooransingh, S.', 'Tempowski, J.', 'Palmer, S.', 'Meredith, T.']",,,,
,PMC,Emerging infections,,PMC1352112,,,,,"Loefler, Imre",,,,
,PMC,"Funding the global control of bird flu: $1.9bn may be peanuts, but it's more than anyone expected",,PMC1352039,,,,,"Roberts, Jennifer A",,,,
,PMC,"Cleavage of the papillomavirus minor capsid protein, L2, at a furin consensus site is necessary for infection",http://dx.doi.org/10.1073/pnas.0508815103,PMC1360554,,,"Papillomaviruses (PV) comprise a large family of nonenveloped DNA viruses that include the oncogenic PV types that are the causative agents of human cervical cancer. As is true of many animal DNA viruses, PV are taken into the cell by endocytosis and must escape from the endosomal compartment to the cytoplasm to initiate infection. Here we show that this step depends on the site-specific enzymatic cleavage of the PV minor virion protein L2 at a consensus furin recognition site. Cleavage by furin, a cell-encoded proprotein convertase, is known to be required for endosome escape by many bacterial toxins. However, to our knowledge, furin has not been previously implicated in the viral entry process. This step is potentially a target for PV inhibition.",,"['Richards, Rebecca M.', 'Lowy, Douglas R.', 'Schiller, John T.', 'Day, Patricia M.']",,,,
,PMC,Expression of dendritic cell-specific intercellular adhesion molecule 3 grabbing nonintegrin on dendritic cells generated from human peripheral blood monocytes,http://dx.doi.org/10.3748/wjg.v12.i3.453,PMC4066067,,,"AIM: To generate dendritic cells (DCs) from human peripheral blood and to detect the expression of dendritic cell-specific intercellular adhesion molecule 3 grabbing nonintegrin (DC-SIGN; CD209) for the further study of DC-SIGN in hepatitis C virus (HCV) transmission. METHODS: Peripheral blood monocytes were isolated from blood of healthy individuals by Ficoll£Hypaque sedimentation and cultured in complete medium containing rhGM-CSF and rhIL-4. Cells were cultured for seven days, with cytokine addition every two days to obtain immature DCs. Characteristics of the cultured cells were observed under light and scanning microscope, and the expression of DC-SIGN was detected by immunofluorescence staining. RESULTS: After seven-day culture, a large number of cells with typical characteristics of DCs appeared. Their characteristics were observed under light and scanning electron microscope. These cells had a variety of cell shapes such as those of bipolar elongate cells, elaborate stellate cells and DCs. DC-SIGN was detected by immunofluorescence staining and its expression level on cultivated dendritic cells was high. CONCLUSION: DCs with a high expression of DC-SIGN can be generated from human peripheral blood monocytes in complete medium containing rhGM-CSF and rhIL-4.",,"['Li, Jun', 'Feng, Zhi-Hua', 'Li, Guang-Yu', 'Mou, Dan-Lei', 'Nie, Qing-He']",,,,
,PMC,Heterogeneous shedding of Escherichia coli O157 in cattle and its implications for control,http://dx.doi.org/10.1073/pnas.0503776103,PMC1325964,,,"Identification of the relative importance of within- and between-host variability in infectiousness and the impact of these heterogeneities on the transmission dynamics of infectious agents can enable efficient targeting of control measures. Cattle, a major reservoir host for the zoonotic pathogen Escherichia coli O157, are known to exhibit a high degree of heterogeneity in bacterial shedding densities. By relating bacterial count to infectiousness and fitting dynamic epidemiological models to prevalence data from a cross-sectional survey of cattle farms in Scotland, we identify a robust pattern: ≈80% of the transmission arises from the 20% most infectious individuals. We examine potential control options under a range of assumptions about within- and between-host variability in infection dynamics. Our results show that the within-herd basic reproduction ratio, R(0), could be reduced to <1 with targeted measures aimed at preventing infection in the 5% of individuals with the highest overall infectiousness. Alternatively, interventions such as vaccination or the use of probiotics that aim to reduce bacterial carriage could produce dramatic reductions in R(0) by preventing carriage at concentrations corresponding to the top few percent of the observed range of counts. We conclude that a greater understanding of the cause of the heterogeneity in bacterial carriage could lead to highly efficient control measures to reduce the prevalence of E. coli O157.",,"['Matthews, L.', 'Low, J.C.', 'Gally, D. L.', 'Pearce, M. C.', 'Mellor, D. J.', 'Heesterbeek, J. A. P.', 'Chase-Topping, M.', 'Naylor, S. W.', 'Shaw, D. J.', 'Reid, S. W. J.', 'Gunn, G. J.', 'Woolhouse, M. E. J.']",,,,
,PMC,Human metapneumovirus infections in hospitalised infants in Spain,http://dx.doi.org/10.1136/adc.2005.082388,PMC2065958,,,"BACKGROUND: Human metapneumovirus (hMPV) causes lower respiratory tract infections, particularly in young children and the elderly. METHODS: A prospective study was conducted on the clinical characteristics of infants <2 years of age admitted to hospital for respiratory infection and the characteristics of hMPV infections were compared with those of infections caused by respiratory syncytial virus (RSV). Influenza A, B and C viruses, RSV, parainfluenza viruses, and adenoviruses were simultaneously detected in clinical samples by multiple reverse transcription nested‐PCR assay. The presence of hMPV was tested in all samples using two separate RT‐PCR tests. RESULTS: A respiratory virus was detected in 65.9% of the 749 children included in the study. hMPV, found in 69 of the positive nasopharyngeal aspirates (14%), was the most common virus after RSV. Peak incidence was in March and over 80% of children were <12 months of age. The most common diagnoses were recurrent wheezing (49.3%) and bronchiolitis (46.4%). Oxygen therapy was required by 58% of patients, and assisted ventilation by one. Clinical characteristics in the 18 co‐infections were indistinguishable from those of single infections. Fifty one hMPV single infections were compared with 88 hRSV single infections. Recurrent wheezing was diagnosed more frequently in hMPV patients. All other variables tested were similar in both groups. CONCLUSIONS: hMPV was the second most frequent virus after RSV in infants <2 years of age hospitalised for respiratory infection and was associated with lower respiratory tract infections. hMPV occurred predominantly in springtime. Co‐infections were frequent and clinically similar to single infections and RSV infections.",,"['García‐García, M L', 'Calvo, C', 'Martín, F', 'Pérez‐Breña, P', 'Acosta, B', 'Casas, I']",,,,
,PMC,Are Traditional Peer-Reviewed Medical Articles Obsolete?: A Pitch for the Wikipedia Concept,,PMC1681971,,,,,"Frishauf, Peter",,,,
,PMC,Surveillance of respiratory virus infections in adult hospital admissions using rapid methods,http://dx.doi.org/10.1017/S0950268805005364,PMC2870437,,,"Both influenza and respiratory syncytial virus (RSV) cause epidemics of respiratory illness of variable severity during the winter season. Influenza in particular has been blamed for hospital winter bed pressures, although it is thought that RSV may also play a role. Human metapneumovirus (hMPV) is a new respiratory virus reported to be important in children; only a limited number of studies are available for adult populations. We aimed to determine initially the burden of virologically confirmed infections, i.e. influenza, RSV and hMPV using polymerase chain reaction (PCR) technology and, in addition, to assess the feasibility of this approach as a surveillance tool for these respiratory viruses. Adult patients admitted to hospital in the previous 24 hours with onset of acute respiratory symptoms in the last 14 days were asked to participate. Informed written consent was obtained and nose and throat swabs taken. Multiplex PCR for influenza A (H1N1 and H3N2), influenza B and RSV A and B were carried out together with a separate PCR for hMPV. A total of 219 patients in 2001–2002 and 216 in 2002–2003 were tested and the combined results for both seasons were: 8 positive for influenza A/H1N1, 14 for influenza A/H3N2, 2 for influenza B, 14 for RSV A and 6 for RSV B. Most patients (261/435) were >65 years and most positives (30/44) were found within this age group. A number of patients aged >65 years who were positive for influenza (12/15) reported having had vaccine. In total, 373 samples were tested for hMPV and 20 were found positive across all age groups except the 45–54 years age group. As influenza activity was low during the study period the impact of infection on admissions could not be assessed. Nevertheless the viruses studied accounted for 15% of hospital admissions for respiratory infection. Most patients were aged >65 years, as expected. In the two years studied RSV and hMPV were each responsible for as many hospitalized cases of respiratory infection as influenza. Influenza infection must be considered even in those who give a history of vaccination. The molecular methods used in this study showed that surveillance of these respiratory viruses can be conducted and may help in the management of patients.",,"['KAYE, M.', 'SKIDMORE, S.', 'OSMAN, H.', 'WEINBREN, M.', 'WARREN, R.']",,,,
,PMC,SUBCELLULAR LOCALIZATION OF SARS-CoV STRUCTURAL PROTEINS,http://dx.doi.org/10.1007/978-0-387-33012-9_51,PMC4524784,,,,,"['Lopez, Lisa A.', 'Jones, Ariel', 'Arndt, William D.', 'Hogue, Brenda G.']",,,,
,PMC,Identification of mouse hepatitis coronavirus A59 nucleocapsid protein phosphorylation sites,http://dx.doi.org/10.1007/978-0-387-33012-9_28,PMC3764311,,,"The coronavirus nucleocapsid (N) is a multifunctional phosphoprotein that encapsidates the genomic RNA into a helical nucleocapsid within the mature virion. The protein also plays roles in viral RNA transcription and/or replication and possibly viral mRNA translation. Phosphorylation is one of the most common post-translation modifications that plays important regulatory roles in modulating protein functions. It has been speculated for sometime that phosphorylation could play an important role in regulation of coronavirus N protein functions. As a first step toward positioning to address this we have identified the amino acids that are phosphorylated on the mouse hepatitis coronavirus (MHV) A59 N protein. High performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was used to identify phosphorylated sites on the N protein from both infected cells and purified extracellular virions. A total of six phosphorylated sites (S162, S170, T177, S389, S424 and T428) were identified on the protein from infected cells. The same six sites were also phosphorylated on the extracellular mature virion N protein. This is the first identification of phosphorylated sites for a group II coronavirus N protein.",,"['White, Tiana C.', 'Yi, Zhengping', 'Hogue, Brenda G.']",,,,
,PMC,ROLE OF MOUSE HEPATITIS CORONAVIRUS ENVELOPE PROTEIN TRANSMEMBRANE DOMAIN,http://dx.doi.org/10.1007/978-0-387-33012-9_32,PMC3764309,,,,,"['Ye, Ye', 'Hogue, Brenda G.']",,,,
,PMC,Importance of MHV-CoV A59 Nucleocapsid Protein COOH-Terminal Negative Charges,http://dx.doi.org/10.1007/978-0-387-33012-9_22,PMC3764308,,,,,"['Bednar, Valerie', 'Verma, Sandhya', 'Blount, Andrew', 'Hogue, Brenda G.']",,,,
,PMC,HUMAN CORONAVIRUS-NL63 INFECTION IS NOT ASSOCIATED WITH ACUTE KAWASAKI DISEASE,http://dx.doi.org/10.1007/978-0-387-33012-9_94,PMC2868826,,,,,"['Baker, S. C.', 'Shimizu, C.', 'Shike, H.', 'Garcia, F.', 'van der Hoek, L.', 'Kuijper, T. W.', 'Reed, S. L.', 'Rowley, A. H.', 'Shulman, S. T.', 'Talbot, H. K. B.', 'Williams, J. V.', 'Burns, J. C.']",,,,
,PMC,PERSISTENT CORONAVIRUS INFECTION OF PROGENITOR OLIGODENDROCYTES,,PMC2562712,,,,,"['Liu, Yin', 'Zhang, Xuming']",,,,
,PMC,DIFFERENTIAL INDUCTION OF PROINFLAMMATORY CYTOKINES IN PRIMARY MOUSE ASTROCYTES AND MICROGLIA BY CORONAVIRUS INFECTION,,PMC1851930,,,,,"['Yu, Dongdong', 'Zhang, Xuming']",,,,
,PMC,Global Transport Networks and Infectious Disease Spread,http://dx.doi.org/10.1016/S0065-308X(05)62009-X,PMC3145127,,,"Air, sea and land transport networks continue to expand in reach, speed of travel and volume of passengers and goods carried. Pathogens and their vectors can now move further, faster and in greater numbers than ever before. Three important consequences of global transport network expansion are infectious disease pandemics, vector invasion events and vector-borne pathogen importation. This review briefly examines some of the important historical examples of these disease and vector movements, such as the global influenza pandemics, the devastating Anopheles gambiae invasion of Brazil and the recent increases in imported Plasmodium falciparum malaria cases. We then outline potential approaches for future studies of disease movement, focussing on vector invasion and vector-borne disease importation. Such approaches allow us to explore the potential implications of international air travel, shipping routes and other methods of transport on global pathogen and vector traffic.",,"['Tatem, A.J.', 'Rogers, D.J.', 'Hay, S.I.']",,,,
,PMC,Avian Influenza: Virchow’s Reminder,,PMC1592674,,,,,"Brown, Corrie",,,,
,PMC,Use of Medical Robotics in Biothreat Situations,,PMC1839714,,,"SARS, Avian Flu and other infectious and potentially highly transmissible diseases are threats to the entire healthcare workforce. Complete bio-isolation or the use of biohazard suits are not practical solutions for routine day-to-day patient-doctor interactions with highly infectious patients. The authors share their initial research experiences with utilizing medical robots for teleconferencing and other clinical activities to overcome these hurdles.",,"['Kartoun, Uri', 'Feied, Craig', 'Gillam, Michael', 'Handler, Jonathan', 'Stern, Helman', 'Smith, Mark']",,,,
,PMC,"Analysis of Information Needs of Users of MEDLINEplus, 2002 – 2003",,PMC1839623,,,"We analyzed query logs from use of MEDLINEplus to answer the questions: Are consumers’ health information needs stable over time? and To what extent do users’ queries change over time? To determine log stability, we assessed an Overlap Rate (OR) defined as the number of unique queries common to two adjacent months divided by the total number of unique queries in those months. All exactly matching queries were considered as one unique query. We measured ORs for the top 10 and 100 unique queries of a month and compared these to ORs for the following month. Over ten months, users submitted 12,234,737 queries; only 2,179,571 (17.8%) were unique and these had a mean word count of 2.73 (S.D., 0.24); 121 of 137 (88.3%) unique queries each comprised of exactly matching search term(s) used at least 5000 times were of only one word. We could predict with 95% confidence that the monthly OR for the top 100 unique queries would lie between 67% – 87% when compared with the top 100 from the previous month. The mean month-to-month OR for top 10 queries was 62% (S.D., 20%) indicating significant variability; the lowest OR of 33% between the top 10 in Mar. compared to Apr. was likely due to “new” interest in information about SARS pneumonia in Apr. 2003. Consumers’ health information needs are relatively stable and the 100 most common unique queries are about 77% the same from month to month. Website sponsors should provide a broad range of information about a relatively stable number of topics. Analyses of log similarity may identify media-induced, cyclical, or seasonal changes in areas of consumer interest.",,"['Scott-Wright, Alicia', 'Crowell, Jon', 'Zeng, Qing', 'Bates, David W.', 'Greenes, Robert']",,,,
,PMC,Long-Distance RNA-RNA Interactions in Plant Virus Gene Expression and Replication,http://dx.doi.org/10.1146/annurev.phyto.44.070505.143353,PMC1894749,,,"The vast majority of plant and animal viruses have RNA genomes. Viral gene expression and replication are controlled by cis-acting elements in the viral genome, which have been viewed conventionally as localized structures. However, recent research has altered this perception and provided compelling evidence for cooperative activity involving distantly positioned RNA elements. This chapter focuses on viral RNA elements that interact across hundreds or thousands of intervening nucleotides to control translation, genomic RNA synthesis, and subgenomic mRNA transcription. We discuss evidence supporting the existence and function of the interactions, and speculate on the regulatory roles that such long-distance interactions play in the virus life cycle. We emphasize viruses in the Tombusviridae and Luteoviridae families in which long-distance interactions are best characterized, but similar phenomena in other viruses are also discussed. Many more examples likely remain undiscovered.",,"['Miller, W. Allen', 'White, K. Andrew']",,,,
,PMC,Evaluation of Affymetrix Severe Acute Respiratory Syndrome Resequencing GeneChips in Characterization of the Genomes of Two Strains of Coronavirus Infecting Humans,http://dx.doi.org/10.1128/AEM.72.1.207-211.2006,PMC1352236,,,"Severe acute respiratory syndrome (SARS) was discovered during a recent global outbreak of atypical pneumonia. A number of immunologic and molecular studies of the clinical samples led to the conclusion that a novel coronavirus (SARS-CoV) was associated with the outbreak. Later, a SARS resequencing GeneChip was developed by Affymetrix to characterize the complete genome of SARS-CoV on a single GeneChip. The present study was carried out to evaluate the performance of SARS resequencing GeneChips. Two human SARS-CoV strains (CDC#200301157 and Urbani) were resequenced by the SARS GeneChips. Five overlapping PCR amplicons were generated for each strain and hybridized with these GeneChips. The successfully hybridized GeneChips generated nucleotide sequences of nearly complete genomes for the two SARS-CoV strains with an average call rate of 94.6%. Multiple alignments of nucleotide sequences obtained from SARS GeneChips and conventional sequencing revealed full concordance. Furthermore, the GeneChip-based analysis revealed no additional polymorphic sites. The results of this study suggest that GeneChip-based genome characterization is fast and reproducible. Thus, SARS resequencing GeneChips may be employed as an alternate tool to obtain genome sequences of SARS-CoV strains pathogenic for humans in order to further understand the transmission dynamics of these viruses.",,"['Sulaiman, Irshad M.', 'Liu, Xin', 'Frace, Michael', 'Sulaiman, Nikhat', 'Olsen-Rasmussen, Melissa', 'Neuhaus, Elizabeth', 'Rota, Paul A.', 'Wohlhueter, Robert M.']",,,,
,PMC,Passive protection of dogs against clinical disease due to Canine parvovirus-2 by specific antibody from chicken egg yolk,,PMC1325096,,,"The protective effect of immunoglobulins derived from chicken egg yolk (IgY) against infection by Canine parvovirus 2 (CPV-2) was evaluated in 10 beagle dogs orally challenged with a strain of the virus. The 2-mo-old dogs were divided into 3 groups and treated with powders containing CPV-2 IgY or normal egg yolk for 7 d after the challenge. The 4 dogs receiving normal egg yolk (control group) demonstrated mild symptoms typical of CPV-2 infection, such as vomiting, diarrhea, and weight loss. No symptoms were observed by 16 d after challenge in the 3 dogs receiving 2 g of IgY powder. Of the 3 dogs receiving 0.5 g of IgY powder, 2 had clinical CPV-2 disease; however, the manifestations were less severe than in the control group. Furthermore, the IgY-treated groups had significantly greater weight gain and shorter duration of virus shedding than the control group. These results indicate that IgY is useful in protecting dogs from CPV-2-induced clinical disease.",,"['Van Nguyen, Sa', 'Umeda, Kouji', 'Yokoyama, Hideaki', 'Tohya, Yukinobu', 'Kodama, Yoshikatsu']",,,,
,PMC,Evaluation of systems for reducing the transmission of Porcine reproductive and respiratory syndrome virus by aerosol,,PMC1325091,,,"The purpose of this study was to compare 3 methods for the reduction of aerosol transmission of Porcine reproductive and respiratory syndrome virus (PRRSV): high-efficiency particulate air (HEPA) filtration, low-cost filtration, and ultraviolet light (UV) irradiation. The HEPA-filtration system involved a pre-filter screen, a bag filter (EU8 rating), and a HEPA filter (EU13 rating). The low-cost-filtration system contained mosquito netting (pre-filter), a fiberglass furnace filter, and an electrostatic furnace filter. For UV irradiation, a lamp emitted UVC radiation at 253.7 nm. No form of intervention was used in the control group. The experimental facilities consisted of 2 chambers connected by a 1.3-m-long duct. Recipient pigs, housed in chamber 2, were exposed to artificial aerosols created by a mechanically operated mister containing modified live PRRSV vaccine located in chamber 1. Aerosol transmission of PRRSV occurred in 9 of the 10 control replicates, 8 of the 10 UVC-irradiation replicates, 4 of the 10 low-cost-filtration replicates, and 0 of the 10 HEPA-filtration replicates. When compared with no intervention, HEPA filtration and low-cost filtration significantly reduced PRRSV transmission (P < 0.0005 and = 0.0286, respectively), whereas UV irradiation had no effect (P = 0.5). However, low-cost filtration and UV irradiation were significantly less effective (P = 0.043 and P < 0.0005, respectively) than HEPA filtration. In conclusion, under the conditions of this study, HEPA filtration was significantly more effective at reducing aerosol transmission of PRRSV than the other methods evaluated.",,"['Dee, Scott A.', 'Batista, Laura', 'Deen, John', 'Pijoan, Carlos']",,,,
,PMC,Risk of ruling out severe acute respiratory syndrome by ruling in another diagnosis: Variable incidence of atypical bacteria coinfection based on diagnostic assays,,PMC2539008,,,"BACKGROUND: Severe acute respiratory syndrome (SARS) caused the first epidemic of the 21st century and continues to threaten the global community. OBJECTIVE: To assess the incidence of coinfection in patients confirmed to have SARS-associated coronavirus (SARS-CoV) infection, and thus, to determine the risk of ruling out SARS by ruling in another diagnosis. METHODS: The present report is a retrospective study evaluating the incidence and impact of laboratory-confirmed SARS-CoV and other pulmonary pathogens in 117 patients. These patients were evaluated in a Toronto, Ontario, community hospital identified as the epicentre for the second SARS outbreak. RESULTS: Coinfection with other pulmonary pathogens occured in patients with SARS. Seventy-three per cent of the patient population evaluated had laboratory-confirmed SARS-CoV infection. Serology showing acute or recent Chlamydophila pneumoniae or Mycoplasma pneumoniae infection revealed an incidence of 30% and 9%, respectively, in those with SARS. These rates are similar to previously published studies on coinfection in pneumonia. All nucleic acid diagnostic assays were negative for C pneumoniae and M pneumoniae in respiratory samples from patients with SARS having serological evidence for these atypical pathogens. CONCLUSIONS: Diagnostic assays for well-recognized pulmonary pathogens have limitations, and ruling out SARS-CoV by ruling in another pulmonary pathogen carries significant risk. Despite positive serology for atypical pathogens, in a setting where clinical suspicion for SARS is high, specific tests for SARS should be performed to confirm or exclude a diagnosis.",,"['Zahariadis, George', 'Gooley, Ted A', 'Ryall, Phyllis', 'Hutchinson, Christine', 'Latchford, Mary I', 'Fearon, Margaret A', 'Jamieson, Frances B', 'Richardson, Susan', 'Kuschak, Theodore', 'Mederski, Barbara']",,,,
,PMC,Real-Time PCR in Clinical Microbiology: Applications for Routine Laboratory Testing,http://dx.doi.org/10.1128/CMR.19.1.165-256.2006,PMC1360278,,,"Real-time PCR has revolutionized the way clinical microbiology laboratories diagnose many human microbial infections. This testing method combines PCR chemistry with fluorescent probe detection of amplified product in the same reaction vessel. In general, both PCR and amplified product detection are completed in an hour or less, which is considerably faster than conventional PCR detection methods. Real-time PCR assays provide sensitivity and specificity equivalent to that of conventional PCR combined with Southern blot analysis, and since amplification and detection steps are performed in the same closed vessel, the risk of releasing amplified nucleic acids into the environment is negligible. The combination of excellent sensitivity and specificity, low contamination risk, and speed has made real-time PCR technology an appealing alternative to culture- or immunoassay-based testing methods for diagnosing many infectious diseases. This review focuses on the application of real-time PCR in the clinical microbiology laboratory.",,"['Espy, M. J.', 'Uhl, J. R.', 'Sloan, L. M.', 'Buckwalter, S. P.', 'Jones, M. F.', 'Vetter, E. A.', 'Yao, J. D. C.', 'Wengenack, N. L.', 'Rosenblatt, J. E.', 'Cockerill, F. R.', 'Smith, T. F.']",,,,
,PMC,"Molecular Mimicry, Bystander Activation, or Viral Persistence: Infections and Autoimmune Disease",http://dx.doi.org/10.1128/CMR.19.1.80-94.2006,PMC1360274,,,"Virus infections and autoimmune disease have long been linked. These infections often precede the occurrence of inflammation in the target organ. Several mechanisms often used to explain the association of autoimmunity and virus infection are molecular mimicry, bystander activation (with or without epitope spreading), and viral persistance. These mechanisms have been used separately or in various combinations to account for the immunopathology observed at the site of infection and/or sites of autoimmune disease, such as the brain, heart, and pancreas. These mechanisms are discussed in the context of multiple sclerosis, myocarditis, and diabetes, three immune-medicated diseases often linked with virus infections.",,"['Fujinami, Robert S.', 'von Herrath, Matthias G.', 'Christen, Urs', 'Whitton, J. Lindsay']",,,,
,PMC,Understanding Helicases as a Means of Virus Control,,PMC3571686,,,"Helicases are promising antiviral drug targets because their enzymatic activities are essential for viral genome replication, transcription, and translation. Numerous potent inhibitors of helicases encoded by herpes simplex virus, severe acute respiratory syndrome coronavirus, hepatitis C virus, Japanese encephalitis virus, West Nile virus, and human papillomavirus have been recently reported in the scientific literature. Some inhibitors have also been shown to decrease viral replication in cell culture and animal models. This review discusses recent progress in understanding the structure and function of viral helicases to help clarify how these potential antiviral compounds function and to facilitate the design of better inhibitors. The above helicases and all related viral proteins are classified here based on their evolutionary and functional similarities, and the key mechanistic features of each group are noted. All helicases share a common motor function fueled by ATP hydrolysis, but differ in exactly how the motor moves the protein and its cargo on a nucleic acid chain. The helicase inhibitors discussed here influence rates of helicase-catalyzed DNA (or RNA) unwinding by preventing ATP hydrolysis, nucleic acid binding, nucleic acid release, or by disrupting the interaction of a helicase with a required cofactor.",,"['Frick, D. N.', 'Lam, A. M. I.']",,,,
,PMC,“Will the SARS epidemic recur?” A retrospective analysis of the experts' opinions,,PMC2465544,,,,,"Wai Wong, Tze",,,,
,PMC,Using Videotaped Vignettes to Teach Medical Students to Perform the Neurologic Examination,http://dx.doi.org/10.1111/j.1525-1497.2005.00271_2.x,PMC1484627,,,,,"['Lim, Erle CH', 'Ong, Benjamin KC', 'Seet, Raymond CS']",,,,
,PMC,Potent Neutralization of Hendra and Nipah Viruses by Human Monoclonal Antibodies,http://dx.doi.org/10.1128/JVI.80.2.891-899.2006,PMC1346873,,,"Hendra virus (HeV) and Nipah virus (NiV) are closely related emerging viruses comprising the Henipavirus genus of the Paramyxovirinae. Each has a broad species tropism and can cause disease with high mortality in both animal and human hosts. These viruses infect cells by a pH-independent membrane fusion event mediated by their attachment (G) and fusion (F) envelope glycoproteins (Envs). Seven Fabs, m101 to -7, were selected for their significant binding to a soluble form of Hendra G (sG) which was used as the antigen for panning of a large naïve human antibody library. The selected Fabs inhibited, to various degrees, cell fusion mediated by the HeV or NiV Envs and virus infection. The conversion of the most potent neutralizer of infectious HeV, Fab m101, to immunoglobulin G1 (IgG1) significantly increased its cell fusion inhibitory activity: the 50% inhibitory concentration was decreased more than 10-fold to approximately 1 μg/ml. The IgG1 m101 was also exceptionally potent in neutralizing infectious HeV; complete (100%) neutralization was achieved with 12.5 μg/ml, and 98% neutralization required only 1.6 μg/ml. The inhibition of fusion and infection correlated with binding of the Fabs to full-length G as measured by immunoprecipitation and less with binding to sG as measured by enzyme-linked immunosorbent assay and Biacore. m101 and m102 competed with the ephrin-B2, which we recently identified as a functional receptor for both HeV and NiV, indicating a possible mechanism of neutralization by these antibodies. The m101, m102, and m103 antibodies competed with each other, suggesting that they bind to overlapping epitopes which are distinct from the epitopes of m106 and m107. In an initial attempt to localize the epitopes of m101 and m102, we measured their binding to a panel of 11 G alanine-scanning mutants and identified two mutants, P185A and Q191 K192A, which significantly decreased binding to m101 and one, G183, which decreased binding of m102 to G. These results suggest that m101 to -7 are specific for HeV or NiV or both and exhibit various neutralizing activities; they are the first human monoclonal antibodies identified against these viruses and could be used for treatment, prophylaxis, and diagnosis and as research reagents and could aid in the development of vaccines.",,"['Zhu, Zhongyu', 'Dimitrov, Antony S.', 'Bossart, Katharine N.', 'Crameri, Gary', 'Bishop, Kimberly A.', 'Choudhry, Vidita', 'Mungall, Bruce A.', 'Feng, Yan-Ru', 'Choudhary, Anil', 'Zhang, Mei-Yun', 'Feng, Yang', 'Wang, Lin-Fa', 'Xiao, Xiaodong', 'Eaton, Bryan T.', 'Broder, Christopher C.', 'Dimitrov, Dimiter S.']",,,,
,PMC,7a Protein of Severe Acute Respiratory Syndrome Coronavirus Inhibits Cellular Protein Synthesis and Activates p38 Mitogen-Activated Protein Kinase,http://dx.doi.org/10.1128/JVI.80.2.785-793.2006,PMC1346853,,,"It was recently shown that the 7a protein of severe acute respiratory syndrome coronavirus induces biochemical changes associated with apoptosis. In this study, the mechanism by which the 7a protein induces apoptosis was examined. The 7a protein was tested for the ability to inhibit cellular gene expression because several proapoptotic viral proteins with this function have previously been identified. 7a protein inhibited expression of luciferase from an mRNA construct that specifically measures translation, whereas inhibitors of transcription and nucleocytoplasmic transport did not. The inhibition of translation and other cellular processes of gene expression have been associated with the induction of a stress response in cells. Western blot analysis using phosphospecific antibodies indicated that 7a protein activated p38 mitogen-activated protein kinase (MAPK), but not c-Jun N-terminal protein kinase/stress-activated protein kinase. Taken together, these data indicate that the induction of apoptosis by the 7a protein may be related to its ability to inhibit cellular translation and activate p38 MAPK.",,"['Kopecky-Bromberg, Sarah A.', 'Martinez-Sobrido, Luis', 'Palese, Peter']",,,,
,PMC,Identification of 5′ and 3′ cis-Acting Elements of the Porcine Reproductive and Respiratory Syndrome Virus: Acquisition of Novel 5′ AU-Rich Sequences Restored Replication of a 5′-Proximal 7-Nucleotide Deletion Mutant,http://dx.doi.org/10.1128/JVI.80.2.723-736.2006,PMC1346850,,,"We here demonstrate the successful engineering of the RNA genome of porcine reproductive and respiratory syndrome virus (PRRSV) by using an infectious cDNA as a bacterial artificial chromosome. Runoff transcription from this cDNA by SP6 polymerase resulted in capped synthetic RNAs bearing authentic 5′ and 3′ ends of the viral genome that had specific infectivities of >5 × 10(5) PFU/μg of RNA. The synthetic viruses recovered from the transfected cells were genotypically and phenotypically indistinguishable from the parental virus. Using our system, a series of genomic RNAs with nucleotide deletions in their 5′ ends produced viruses with decreased or no infectivity. Various pseudorevertants were isolated, and acquisition of novel 5′ sequences of various sizes, composed predominantly of A and U bases, restored their infectivities, providing a novel insight into functional elements of the 5′ end of the PRRSV genome. In addition, our system was further engineered to generate a panel of self-replicating, self-limiting, luciferase-expressing PRRSV viral replicons bearing various deletions. Analysis of these replicons revealed the presence and location of a 3′ cis-acting element in the genome that was required for replication. Moreover, we produced enhanced green fluorescent protein-expressing infectious viruses, which indicates that the PRRSV cDNA/viral replicon/recombinant virus can be developed as a vector for the expression of a variety of heterologous genes. Thus, our PRRSV reverse genetics system not only offers a means of directly investigating the molecular mechanisms of PRRSV replication and pathogenesis but also can be used to generate new heterologous gene expression vectors and genetically defined antiviral vaccines.",,"['Choi, Yu-Jeong', 'Yun, Sang-Im', 'Kang, Shien-Young', 'Lee, Young-Min']",,,,
,PMC,Defining the Cellular Target(s) of Porcine Reproductive and Respiratory Syndrome Virus Blocking Monoclonal Antibody 7G10,http://dx.doi.org/10.1128/JVI.80.2.689-696.2006,PMC1346842,,,"We produced a monoclonal antibody (MAb) (7G10) that has blocking activity against porcine reproductive and respiratory syndrome virus (PRRSV). In this study, we identified the components of the 7G10 MAb-bound complex as cytoskeletal filaments: vimentin, cytokeratin 8, cytokeratin 18, actin, and hair type II basic keratin. Vimentin bound to PRRSV nucleocapsid protein and anti-vimentin antibodies showed PRRSV-blocking activity. Vimentin was expressed on the surface of MARC-145, a PRRSV-susceptible cell line. Simian vimentin rendered BHK-21 and CRFK, nonsusceptible cell lines, susceptible to PRRSV infection. These results suggest that vimentin is part of the PRRSV receptor complex and that it plays an important role in PRRSV binding with the other cytoskeletal filaments that mediate transportation of the virus in the cytosol.",,"['Kim, Jeong-Ki', 'Fahad, Al-Majhdi', 'Shanmukhappa, Kumar', 'Kapil, Sanjay']",,,,
,PMC,"Live-Cell Characterization and Analysis of a Clinical Isolate of Bovine Respiratory Syncytial Virus, Using Molecular Beacons",http://dx.doi.org/10.1128/JVI.80.2.682-688.2006,PMC1346841,,,"Understanding viral pathogenesis is critical for prevention of outbreaks, development of antiviral drugs, and biodefense. Here, we utilize molecular beacons to directly detect the viral genome and characterize a clinical isolate of bovine respiratory syncytial virus (bRSV) in living cells. Molecular beacons are dual-labeled, hairpin oligonucleotide probes with a reporter fluorophore at one end and a quencher at the other; they are designed to fluoresce only when hybridizing to a complementary target. By imaging the fluorescence signal of molecular beacons, the spread of bRSV was monitored for 7 days with a signal-to-noise ratio of 50 to 200, and the measured time course of infection was quantified with a mathematical model for viral growth. We found that molecular beacon signal could be detected in single living cells infected with a viral titer of 2 × 10(3.6) 50% tissue culture infective doses/ml diluted 1,000 fold, demonstrating high detection sensitivity. Low background in uninfected cells and simultaneous staining of fixed cells with molecular beacons and antibodies showed high detection specificity. Furthermore, using confocal microscopy to image the viral genome in live, infected cells, we observed a connected, highly three-dimensional, amorphous inclusion body structure not seen in fixed cells. Taken together, the use of molecular beacons for active virus imaging provides a powerful tool for rapid viral infection detection, the characterization of RNA viruses, and the design of new antiviral drugs.",,"['Santangelo, Philip', 'Nitin, Nitin', 'LaConte, Leslie', 'Woolums, Amelia', 'Bao, Gang']",,,,
,PMC,Monoclonal Antibodies Targeting the HR2 Domain and the Region Immediately Upstream of the HR2 of the S Protein Neutralize In Vitro Infection of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.80.2.941-950.2006,PMC1346840,,,"We have previously shown that an Escherichia coli-expressed, denatured spike (S) protein fragment of the severe acute respiratory coronavirus, containing residues 1029 to 1192 which include the heptad repeat 2 (HR2) domain, was able to induce neutralizing polyclonal antibodies (C. T. Keng, A. Zhang, S. Shen, K. M. Lip, B. C. Fielding, T. H. Tan, C. F. Chou, C. B. Loh, S. Wang, J. Fu, X. Yang, S. G. Lim, W. Hong, and Y. J. Tan, J. Virol. 79:3289-3296, 2005). In this study, monoclonal antibodies (MAbs) were raised against this fragment to identify the linear neutralizing epitopes in the functional domain and to investigate the mechanisms involved in neutralization. Eighteen hybridomas secreting the S protein-specific MAbs were obtained. Binding sites of these MAbs were mapped to four linear epitopes. Two of them were located within the HR2 region and two immediately upstream of the HR2 domain. MAbs targeting these epitopes showed in vitro neutralizing activities and were able to inhibit cell-cell membrane fusion. These results provide evidence of novel neutralizing epitopes that are located in the HR2 domain and the spacer region immediately upstream of the HR2 of the S protein.",,"['Lip, Kuo-Ming', 'Shen, Shuo', 'Yang, Xiaoming', 'Keng, Choong-Tat', 'Zhang, Aihua', 'Oh, Hsueh-Ling Janice', 'Li, Zhi-Hong', 'Hwang, Le-Ann', 'Chou, Chih-Fong', 'Fielding, Burtram C.', 'Tan, Timothy H. P.', 'Mayrhofer, Josef', 'Falkner, Falko G.', 'Fu, Jianlin', 'Lim, Seng Gee', 'Hong, Wanjin', 'Tan, Yee-Joo']",,,,
,PMC,Identification and Characterization of a Penaeus monodon Lymphoid Cell-Expressed Receptor for the Yellow Head Virus,http://dx.doi.org/10.1128/JVI.80.1.262-269.2006,PMC1317559,,,"The yellow head virus is a positive-sense, single-stranded RNA virus that causes significant mortality in farmed penaeid shrimp. This study sought to isolate and characterize the receptor protein used by the virus to gain entry into Penaeus monodon Oka (lymphoid) organ cells, a primary target of yellow head virus infections. Virus overlay protein binding assay on Oka organ membrane preparations identified a 65-kDa protein, and antibodies raised against this protein inhibited virus entry in primary Oka cell cultures by approximately 80%. N-terminal sequence analysis of the 65-kDa protein generated a 17-amino acid peptide fragment which was used to design degenerate primers that amplified a 1.5-kbp product from Oka organ total RNA, which was cloned and sequenced. Northern analysis and PCR were used to confirm a single RNA transcript that was expressed in most tissues. Subsequently, the mature cDNA was recloned and the expressed protein shown to cross-react with the antibody raised against the original virus binding band. Down regulation of the message through double-stranded RNA-mediated RNA interference silencing resulted in the complete inhibition of virus entry. While the identity of the clone remains unknown, it nevertheless represents the first invertebrate Nidovirus receptor isolated to date.",,"['Assavalapsakul, Wanchai', 'Smith, Duncan R.', 'Panyim, Sakol']",,,,
,PMC,ICP0 Prevents RNase L-Independent rRNA Cleavage in Herpes Simplex Virus Type 1-Infected Cells,http://dx.doi.org/10.1128/JVI.80.1.218-225.2006,PMC1317541,,,"The classical interferon (IFN)-dependent antiviral response to viral infection involves the regulation of IFN-stimulated genes (ISGs), one being the gene encoding cellular endoribonuclease RNase L, which arrests protein synthesis and induces apoptosis by nonspecifically cleaving rRNA. Recently, the herpes simplex virus type 1 (HSV-1) protein ICP0 has been shown to block the induction of ISGs by subverting the IFN pathway upstream of the 2′-5′-oligoadenylate synthetase (OAS)/RNase L pathway. We report that ICP0 also prevents rRNA degradation at late stages of HSV-1 infection, independent of its E3 ubiquitin ligase activity, and that the resultant rRNA degradation is independent of the classical RNase L antiviral pathway. Moreover, the degradation is independent of the viral RNase vhs and is independent of IFN response factor 3. These studies indicate the existence of another, previously unidentified, RNase that is part of the host antiviral response to viral infection.",,"['Sobol, Paul T.', 'Mossman, Karen L.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus 3a Protein Is Released in Membranous Structures from 3a Protein-Expressing Cells and Infected Cells,http://dx.doi.org/10.1128/JVI.80.1.210-217.2006,PMC1317539,,,"Severe acute respiratory syndrome coronavirus (SCoV) accessory protein 3a is a virus structural protein. We demonstrate here that 3a protein was released efficiently in membranous structures from various cell lines expressing 3a protein. A subpopulation of the released 3a protein is associated with detergent-resistant membranes. The presence of the YxxΦ and diacidic motifs, located within the cytoplasmic tail of the 3a protein, was not required for its efficient release. Analysis of supernatant from SCoV-infected cells with sucrose gradient sedimentation and virus capture assay indicated that the 3a protein was released from infected cells in two distinct populations, as a component of SCoV particles, and in membrane structures with a lower buoyant density. These data provide new insights into the biological properties of SCoV 3a protein.",,"['Huang, Cheng', 'Narayanan, Krishna', 'Ito, Naoto', 'Peters, C. J.', 'Makino, Shinji']",,,,
,PMC,Neither the RNA nor the Proteins of Open Reading Frames 3a and 3b of the Coronavirus Infectious Bronchitis Virus Are Essential for Replication,http://dx.doi.org/10.1128/JVI.80.1.296-305.2006,PMC1317528,,,"Gene 3 of infectious bronchitis virus is tricistronic; open reading frames (ORFs) 3a and 3b encode two small nonstructural (ns) proteins, 3a and 3b, of unknown function, and a third, structural protein E, is encoded by ORF 3c. To determine if either the 3a or the 3b protein is required for replication, we first modified their translation initiation codons to prevent translation of the 3a and 3b proteins from recombinant infectious bronchitis viruses (rIBVs). Replication in primary chick kidney (CK) cells and in chicken embryos was not affected. In chicken tracheal organ cultures (TOCs), the recombinant rIBVs reached titers similar to those of the wild-type virus, but in the case of viruses lacking the 3a protein, the titer declined reproducibly earlier. Translation of the IBV E protein is believed to be initiated by internal entry of ribosomes at a structure formed by the sequences corresponding to ORFs 3a and 3b. To assess the necessity of this mechanism, we deleted most of the sequence representing 3a and 3b to produce a gene in which ORF 3c (E) was adjacent to the gene 3 transcription-associated sequence. Western blot analysis revealed that the recombinant IBV produced fivefold less E protein. Nevertheless, titers produced in CK cells, embryos, and TOCs were similar to those of the wild-type virus, although they declined earlier in TOCs, probably due to the absence of the 3a protein. Thus, neither the tricistronic arrangement of gene 3, the internal initiation of translation of E protein, nor the 3a and 3b proteins are essential for replication per se, suggesting that these proteins are accessory proteins that may have roles in vivo.",,"['Hodgson, Teri', 'Britton, Paul', 'Cavanagh, Dave']",,,,
,PMC,Host Deadenylation-Dependent mRNA Decapping Factors Are Required for a Key Step in Brome Mosaic Virus RNA Replication,http://dx.doi.org/10.1128/JVI.80.1.246-251.2006,PMC1317526,,,"The genomes of positive-strand RNA [(+)RNA] viruses perform two mutually exclusive functions: they act as mRNAs for the translation of viral proteins and as templates for viral replication. A universal key step in the replication of (+)RNA viruses is the coordinated transition of the RNA genome from the cellular translation machinery to the viral replication complex. While host factors are involved in this step, their nature is largely unknown. By using the ability of the higher eukaryotic (+)RNA virus brome mosaic virus (BMV) to replicate in yeast, we previously showed that the host Lsm1p protein is required for efficient recruitment of BMV RNA from translation to replication. Here we show that in addition to Lsm1p, all tested components of the Lsm1p-7p/Pat1p/Dhh1p decapping activator complex, which functions in deadenylation-dependent decapping of cellular mRNAs, are required for BMV RNA recruitment for RNA replication. In contrast, other proteins of the decapping machinery, such as Edc1p and Edc2p from the deadenylation-dependent decapping pathway and Upf1p, Upf2p, and Upf3p from the deadenylation-independent decapping pathway, had no significant effects. The dependence of BMV RNA recruitment on the Lsm1p-7p/Pat1p/Dhh1p complex was linked exclusively to the 3′ noncoding region of the BMV RNA. Collectively, our results suggest that the Lsm1p-7p/Pat1p/Dhh1p complex that transfers cellular mRNAs from translation to degradation might act as a key regulator in the switch from BMV RNA translation to replication.",,"['Mas, Antonio', 'Alves-Rodrigues, Isabel', 'Noueiry, Amine', 'Ahlquist, Paul', 'Díez, Juana']",,,,
,PMC,Role of the Mitochondrial Signaling Pathway in Murine Coronavirus-Induced Oligodendrocyte Apoptosis,http://dx.doi.org/10.1128/JVI.80.1.395-403.2006,PMC1317518,,,"A previous study demonstrated that infection of rat oligodendrocytes by mouse hepatitis virus (MHV) resulted in apoptosis, which is caspase dependent (Y. Liu, Y. Cai, and X. Zhang, J. Virol. 77:11952-11963, 2003). Here we determined the involvement of the mitochondrial pathway in MHV-induced oligodendrocyte apoptosis. We found that caspase-9 activity was 12-fold higher in virus-infected cells than in mock-infected cells at 24 h postinfection (p.i.). Pretreatment of cells with a caspase-9 inhibitor completely blocked caspase-9 activation and partially inhibited the apoptosis mediated by MHV infection. Analyses of cytochrome c release further revealed an activation of the mitochondrial apoptotic pathway. Stable overexpression of the two antiapoptotic proteins Bcl-2 and Bcl-xL significantly, though only partially, blocked apoptosis, suggesting that activation of the mitochondrial pathway is partially responsible for the apoptosis. To identify upstream signals, we determined caspase-8 activity, cleavage of Bid, and expression of Bax and Bad by Western blotting. We found a drastic increase in caspase-8 activity and cleavage of Bid at 24 h p.i. in virus-infected cells, suggesting that Bid may serve as a messenger to relay the signals from caspase-8 to mitochondria. However, treatment with a caspase-8 inhibitor only slightly blocked cytochrome c release from the mitochondria. Furthermore, we found that Bax but not Bad was significantly increased at 12 h p.i. in cells infected with both live and UV-inactivated viruses and that Bax activation was partially blocked by treatment with the caspase-8 inhibitor. These results thus establish the involvement of the mitochondrial pathway in MHV-induced oligodendrocyte apoptosis.",,"['Liu, Yin', 'Pu, Yinghui', 'Zhang, Xuming']",,,,
,PMC,Expanded Tropism and Altered Activation of a Retroviral Glycoprotein Resistant to an Entry Inhibitor Peptide,http://dx.doi.org/10.1128/JVI.80.1.353-359.2006,PMC1317511,,,"The envelope of class I viruses can be a target for potent viral inhibitors, such as the human immunodeficiency virus type 1 (HIV-1) inhibitor enfuvirtide, which are derived from the C-terminal heptad repeat (HR2) of the transmembrane (TM) subunit. Resistance to an HR2-based peptide inhibitor of a model retrovirus, subgroup A of the Avian Sarcoma and Leukosis Virus genus (ASLV-A), was studied by examining mutants derived by viral passage in the presence of inhibitor. Variants with reduced sensitivity to inhibitor were readily selected in vitro. Sensitivity determinants were identified for 13 different isolates, all of which mapped to the TM subunit. These determinants were identified in two regions: (i) the N-terminal heptad repeat (HR1) and (ii) the N-terminal segment of TM, between the subunit cleavage site and the fusion peptide. The latter class of mutants identified a region outside of the predicted HR2-binding site that can significantly alter sensitivity to inhibitor. A subset of the HR1 mutants displayed the unanticipated ability to infect nonavian cells. This expanded tropism was associated with increased efficiency of envelope triggering by soluble receptor at low temperatures, as measured by protease sensitivity of the surface subunit (SU) of envelope. In addition, expanded tropism was linked for the most readily triggered mutants with increased sensitivity to neutralization by SU-specific antiserum. These observations depict a class of HR2 peptide-selected mutations with a reduced activation threshold, thereby allowing the utilization of alternative receptors for viral entry.",,"['Amberg, Sean M.', 'Netter, Robert C.', 'Simmons, Graham', 'Bates, Paul']",,,,
,PMC,Crossing the species barrier: the threat of an avian influenza pandemic,,PMC1325277,,,"Avian influenza (H5N1) has recently been recognized as a new emerging infectious disease that may pose a threat to international public health. Most recent developments lead to the belief that H5N1 could become the cause of the next influenza pandemic. This review discusses the characteristics of H5N1 avian influenza virus as an emerging infectious disease with the potential for pandemic development. In addition, the current pandemic influenza alert status and guidelines for pandemic preparedness, treatment, and prevention are discussed.",,"Riedel, Stefan",,,,
,PMC,"Colitis due to Clostridium difficile toxins: underdiagnosed, highly virulent, and nosocomial",,PMC1325276,,,"Clostridium difficile colitis is a major complication of antibiotic therapy. Antibiotics cause a reduction in bacteria that normally reside in the colon. If an antibiotic-treated patient ingests C. difficile bacteria, this organism may proliferate in the colon because it is resistant to most antibiotics and because it does not have to compete with the normal bacteria for nutrients. If the C. difficile organism has the gene for toxin production, the toxin can produce a colitis. In addition to antibiotics, other proposed risk factors for development of C. difficile colitis include advanced age, contact with infected patients and with their health care providers, impaired immune function, suppression of gastric acid secretion by a proton pump inhibitor, and postpyloric tube feeding. Many of the risk factors become simultaneously focused on patients admitted to the hospital. The incidence of C. difficile disease has been rising, and strains have become more virulent. In some forms of the disease, the patient doesn't have diarrhea, and in such patients C. difficile can be deadly but difficult to diagnose. The standard treatment, with metronidazole or vancomycin, fails to work in up to 25% of patients with the fulminant form of colitis. Since C. difficile causes only 20% of cases of antibiotic-associated diarrhea, a specific test is needed to diagnose this organism. Toxigenic cultureis highly specific but not available at most institutions. The tests that are available—enzyme-linked immunosorbent assay and fecal cytotoxicity assay—have high false-negative rates, even in patients with severe clinical disease, creating a diagnostic dilemma. The only proven way to reduce the risk of C. difficile disease is implementation of an antibiotic management program in conjunction with enhanced infection control procedures.",,"Fordtran, John S.",,,,
,PMC,Comparison of SUMO fusion technology with traditional gene fusion systems: Enhanced expression and solubility with SUMO,http://dx.doi.org/10.1110/ps.051812706,PMC2242369,,,"Despite the availability of numerous gene fusion systems, recombinant protein expression in Escherichia coli remains difficult. Establishing the best fusion partner for difficult-to-express proteins remains empirical. To determine which fusion tags are best suited for difficult-to-express proteins, a comparative analysis of the newly described SUMO fusion system with a variety of commonly used fusion systems was completed. For this study, three model proteins, enhanced green florescent protein (eGFP), matrix metalloprotease-13 (MMP13), and myostatin (growth differentiating factor-8, GDF8), were fused to the C termini of maltose-binding protein (MBP), glutathione S-transferase (GST), thioredoxin (TRX), NUS A, ubiquitin (Ub), and SUMO tags. These constructswere expressed in E. coli and evaluated for expression and solubility. As expected, the fusion tags varied in their ability to produce tractable quantities of soluble eGFP, MMP13, and GDF8. SUMO and NUS A fusions enhanced expression and solubility of recombinant proteins most dramatically. The ease at which SUMO and NUS A fusion tags were removed from their partner proteins was then determined. SUMO fusions are cleaved by the natural SUMO protease, while an AcTEV protease site had to be engineered between NUS A and its partner protein. A kinetic analysis showed that the SUMO and AcTEV proteases had similarK(M) values, but SUMOprotease had a 25-fold higher k(cat) than AcTEV protease, indicating a more catalytically efficient enzyme. Taken together, these results demonstrate that SUMO is superior to commonly used fusion tags in enhancing expression and solubility with the distinction of generating recombinant protein with native sequences.",,"['Marblestone, Jeffrey G.', 'Edavettal, Suzanne C.', 'Lim, Yiting', 'Lim, Peter', 'Zuo, Xun', 'Butt, Tauseef R.']",,,,
,PMC,"B. subtilis ykuD Protein at 2.0 Å Resolution: Insights into the Structure and Function of a Novel, Ubiquitous Family of Bacterial Enzymes",http://dx.doi.org/10.1002/prot.20702,PMC2792008,,,"The crystal structure of the product of the Bacillus subtilis ykuD gene was solved by the multiwavelength anomalous dispersion (MAD) method and refined using data to 2.0 Å resolution. The ykuD protein is a representative of a distinctly prokaryotic and ubiquitous family found among both pathogenic and nonpathogenic Gram-positive and Gram-negative bacteria. The deduced amino acid sequence reveals the presence of an N-terminal LysM domain, which occurs among enzymes involved in cell wall metabolism, and a novel, putative catalytic domain with a highly conserved His/Cys-containing motif of hitherto unknown structure. As the wild-type protein did not crystallize, a double mutant was designed (Lys117Ala/Gln118Ala) to reduce excess surface conformational entropy. As expected, the structure of the LysM domain is similar to the NMR structure reported for an analogous domain from Escherichia coli murein transglycosylase MltD. The molecular model also shows that the 112-residue-long C-terminal domain has a novel tertiary fold consisting of a β-sandwich with two mixed sheets, one containing five strands and the other, six strands. The two β-sheets form a cradle capped by an α-helix. This domain contains a putative catalytic site with a tetrad of invariant His123, Gly124, Cys139, and Arg141. The stereochemistry of this active site shows similarities to peptidotransferases and sortases, and suggests that the enzymes of the ykuD family may play an important role in cell wall biology.",,"['Bielnicki, Jakub', 'Devedjiev, Yancho', 'Derewenda, Urszula', 'Dauter, Zbigniew', 'Joachimiak, Andrzej', 'Derewenda, Zygmunt S.']",,,,
,PMC,Emerging Infections: Lessons from the Viral Hemorrhagic Fevers,,PMC1500910,,,"Two Institute of Medicine reports since 1992 have emphasized the dangerous and continuing threat to the world from emerging infectious diseases. Working with viral hemorrhagic fevers provides a number of lessons related to the processes that control emergence, the pattern of disease after emergence, and how to cope with these incidents. This short paper uses two arenavirus hemorrhagic fevers to illustrate some of these principles. Argentine and Bolivian hemorrhagic fevers first came to medical attention in the 1950’s. The forces that underlie the emergence of disease in Argentina are not understood, but the Bolivian episode has a reasonably understandable train of events behind it. The Argentine disease had serious impact on the large agricultural economy, and the ecology of the rodent reservoir did not lend itself to control; a vaccine was developed by Argentina and the U.S. with the latter motivated largely by biodefense. The Bolivian disease was controlled in large part by eliminating rodents that invaded towns, and the impact was subsequently below the level needed to trigger drug or vaccine development. These two viruses were important in the recognition of a new family of viruses (Arenaviridae), and this finding of new taxons during the investigation of emerging infectious diseases continues.",,"Peters, C. J",,,,
,PMC,Immune Regulation of Transgene Expression in the Brain: B Cells Regulate an Early Phase of Elimination of Transgene Expression from Adenoviral Vectors,http://dx.doi.org/10.1089/vim.2006.19.508,PMC1847585,,,"Cellular immune mechanisms that regulate viral gene expression within infected brain cells remain poorly understood. Previous work has shown that systemic immunization against adenovirus after vector delivery to the brain results in complete loss of brain cells infected by adenoviral vectors. Although T cells play an important role in this process, we demonstrate herein that B cells also significantly regulate transgene expression from the CNS. After the systemic immunization against adenovirus of animals injected via the brain with an adenoviral vector 30 days earlier, we uncovered substantial infiltration by CD19(+) B cells of the area of the brain transduced by the virus. This suggests the involvement of B cells in the adaptive immune response-mediated loss of transduced cells from the brain. Confocal analysis of these brains demonstrated physical contacts between transduced brain cells and CD19(+) cells. To test the hypothesis that B cells play a causal role in the loss of infected cells from the brain, we demonstrated that animals devoid of B cells were unable to eliminate transgene expression at early time points after immunization. This demonstrates that B cells play a necessary role in the loss of transgene expression at early, but not late, time points postimmunization. Thus, these data have important implications for our understanding of the role of B cells as immune effectors during the immune-mediated clearance of viral infections from the CNS, and also for understanding mechanisms operating in brain autoimmunity, as well as for the potential safety of clinical gene therapy for brain diseases.",,"['ZIRGER, JEFFREY M.', 'LIU, CHUNYAN', 'BARCIA, CARLOS', 'CASTRO, MARIA G.', 'LOWENSTEIN, PEDRO R.']",,,,
,PMC,Potential Role of High Mobility Group Box 1 in Viral Infectious Diseases,http://dx.doi.org/10.1089/vim.2006.19.3,PMC1782047,,,"A nuclear protein, high mobility group box 1 (HMGB1), is released passively by necrotic cells and actively by macrophages/monocytes in response to exogenous and endogenous inflammatory stimuli. After binding to the receptor for advanced glycation end products (RAGE), or Toll-like receptor 4 (TLR4), HMGB1 activates macrophages/monocytes to express proinflammatory cytokines, chemokines, and adhesion molecules. Pharmacological suppression of its activities or release is protective against lethal endotoxemia and sepsis, establishing HMGB1 as a critical mediator of lethal systemic inflammation. In light of observations that many viruses (e.g., West Nile virus, Salmon anemia virus) can induce passive HMGB1 release, we propose a potential pathogenic role of HMGB1 in viral infectious diseases.",,"['WANG, HAICHAO', 'WARD, MARY F.', 'FAN, XUE-GONG', 'SAMA, ANDREW E.', 'LI, WEI']",,,,
,PMC,High affinity mouse-human chimeric Fab against Hepatitis B surface antigen,http://dx.doi.org/10.3748/wjg.v11.i48.7569,PMC4727235,,,"AIM: Passive immunotherapy using antibody against hepatitis B surface antigen (HBsAg) has been advocated in certain cases of Hepatitis B infection. We had earlier reported on the cloning and expression of a high affinity scFv derived from a mouse monoclonal (5S) against HBsAg. However this mouse antibody cannot be used for therapeutic purposes as it may elicit anti-mouse immune responses. Chimerization by replacing mouse constant domains with human ones can reduce the immunogenicity of this antibody. METHODS: We cloned the V(H) and V(L) genes of this mouse antibody, and fused them with CH1 domain of human IgG1 and C(L) domain of human kappa chain respectively. These chimeric genes were cloned into a phagemid vector. After initial screening using the phage display system, the chimeric Fab was expressed in soluble form in E. coli. RESULTS: The chimeric Fab was purified from the bacterial periplasmic extract. We characterized the chimeric Fab using several in vitro techniques and it was observed that the chimeric molecule retained the high affinity and specificity of the original mouse monoclonal. This chimeric antibody fragment was further expressed in different strains of E. coli to increase the yield. CONCLUSION: We have generated a mouse-human chimeric Fab against HBsAg without any significant loss in binding and epitope specificity. This chimeric Fab fragment can be further modified to generate a full-length chimeric antibody for therapeutic uses.",,"['Bose, Biplab', 'Khanna, Navin', 'Acharya, Subrat K', 'Sinha, Subrata']",,,,
,PMC,Unexpected similarity between the cytosolic West Nile virus NS3 and the secretory furin-like serine proteinases,http://dx.doi.org/10.1042/BJ20051787,PMC1360712,,,"Many viral proteins undergo proteolytic processing events that are required for virus infection and virion assembly. In this issue of Biochemical Journal, Strongin and co-workers report that the NS3 protease from West Nile virus unexpectedly cleaves certain substrates at pairs of basic residues, a specificity that resembles that of the furin-like PCs (proprotein convertases). This led to the demonstration that furin/PC inhibitors containing poly(D-arginine) are also potent inhibitors of NS3, and that anthrax toxin protective antigen and myelin basic protein are potential NS3 substrates. Structural modelling based on Dengue virus NS3 provided a possible rationale for the observed cleavage specificity of West Nile virus NS3.",,"Seidah, Nabil G.",,,,
,PMC,"The SARS outbreak in a general hospital in Tianjin, China – the case of super-spreader",http://dx.doi.org/10.1017/S095026880500556X,PMC2870450,,,"Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease with a high case-fatality rate and devastating socio-economic impact. In this report we summarized the results from an epidemiological investigation of a SARS outbreak in a hospital in Tianjin, between April and May 2003. We collected epidemiological and clinical data on 111 suspect and probable cases of SARS associated with the outbreak. Transmission chain and outbreak clusters were investigated. The outbreak was single sourced and had eight clusters. All SARS cases in the hospital were traced to a single patient who directly infected 33 people. The patients ranged from 16 to 82 years of age (mean age 38·5 years); 38·7% were men. The overall case fatality in the SARS outbreak was 11·7% (13/111). The outbreak lasted around 4 weeks after the index case was identified. SARS is a highly contagious condition associated with substantial case fatality; an outbreak can result from one patient in a relatively short period. However, stringent public health measures seemed to be effective in breaking the disease transmission chain.",,"['WANG, SH.\xa0X.', 'LI, Y.\xa0M.', 'SUN, B.\xa0C.', 'ZHANG, S.\xa0W.', 'ZHAO, W.\xa0H.', 'WEI, M.\xa0T.', 'CHEN, K.\xa0X.', 'ZHAO, X.\xa0L.', 'ZHANG, Z.\xa0L.', 'KRAHN, M.', 'CHEUNG, A.\xa0C.', 'WANG, P.\xa0P.']",,,,
,PMC,SARS Coronavirus E Protein in Phospholipid Bilayers: An X-Ray Study,http://dx.doi.org/10.1529/biophysj.105.072892,PMC1386782,,,"We investigated the structure of the hydrophobic domain of the severe acute respiratory syndrome E protein in model lipid membranes by x-ray reflectivity and x-ray scattering. In particular, we used x-ray reflectivity to study the location of an iodine-labeled residue within the lipid bilayer. The label imposes spatial constraints on the protein topology. Experimental data taken as a function of protein/lipid ratio P/L and different swelling states support the hairpin conformation of severe acute respiratory syndrome E protein reported previously. Changes in the bilayer thickness and acyl-chain ordering are presented as a function of P/L, and discussed in view of different structural models.",,"['Khattari, Z.', 'Brotons, G.', 'Akkawi, M.', 'Arbely, E.', 'Arkin, I. T.', 'Salditt, T.']",,,,
,PMC,Index of Authors,,PMC1613182,,,,,,,,,
,PMC,Index of Subjects,,PMC1613179,,,,,,,,,
,PMC,Hospital planning for acts of terrorism and other public health emergencies involving children,http://dx.doi.org/10.1136/adc.2004.069617,PMC1720234,,,,,"['Chung, S', 'Shannon, M']",,,,
,PMC,Durable engraftment of AMD3100-mobilized autologous and allogeneic peripheral-blood mononuclear cells in a canine transplantation model,http://dx.doi.org/10.1182/blood-2005-05-1937,PMC1895108,,,"Peripheral-blood mononuclear cells (PBMCs) mobilized with AMD3100, a CXCR4 antagonist, combined with granulocyte colony-stimulating factor (G-CSF) have reconstituted autologous hematopoiesis in cancer patients following myeloablative conditioning. The engraftment potential of PBMCs mobilized with AMD3100 alone, however, has remained unproven. We therefore studied AMD3100-mobilized PBMCs in a canine model. Four dogs received 920 cGy total body irradiation (TBI) before infusion of autologous AMD3100-mobilized PBMCs (median CD34 cell count, 3.9 × 10(6)/kg). Neutrophil (> 0.5 × 10(9)/L [500/μL]) and platelet (> 20 ×/10(9)/L [> 20 000/μL]) recoveries occurred at medians of 9 (range, 7-10) days and 25 (range, 23-38) days, respectively, after TBI, and all dogs had normal marrow function at 1 year after transplantation. To evaluate the long-term engraftment potential of AMD3100-mobilized PBMCs, 5 dogs were given 920 cGy TBI followed by infusion of AMD3100-mobilized PBMCs (median CD34 cell dose, 4.7 × 10(6)/kg) from their dog leukocyte antigen (DLA)-identical littermates. Neutrophil and platelet recoveries occurred at medians of 8 (range, 8-10) days and 26 (range, 26-37) days, respectively, after TBI. With a median follow-up of 53 (range, 33-61) weeks, recipients' marrow function was normal, and blood-donor chimerism levels were 97% to 100%. In summary, both autologous and allogeneic AMD3100-mobilized PBMCs led to prompt and durable engraftment in dogs after 920 cGy TBI.",,"['Burroughs, Lauri', 'Mielcarek, Marco', 'Little, Marie-Térèse', 'Bridger, Gary', 'MacFarland, Ron', 'Fricker, Simon', 'Labrecque, Jean', 'Sandmaier, Brenda M.', 'Storb, Rainer']",,,,
,PMC,"Perceptual capacity and the good GP: invisible, yet indispensable for quality of care",,PMC1570505,,,,,"['Gillies, John', 'Sheehan, Mark']",,,,
,PMC,Suspected Clostridium difficile-associated hemorrhagic diarrhea in a 1-week-old elk calf,,PMC1288420,,,"Clostridium difficile-associated diarrhea was suspected in a 1-week-old elk (Cervus elaphus) calf. The isolation of a toxigenic strain of C. difficile from a diarrheic fecal sample, along with exclusion of other enteropathogens, formed the basis of this presumptive diagnosis. Further study is indicated to evaluate the role of C. difficile in neonatal diarrhea in elk.",,"['Arroyo, Luis G.', 'Rousseau, Joyce D.', 'Staempfli, Henry R.', 'Weese, J. Scott']",,,,
,PMC,Longitudinal Analysis of Severe Acute Respiratory Syndrome (SARS) Coronavirus-Specific Antibody in SARS Patients,http://dx.doi.org/10.1128/CDLI.12.12.1455-1457.2005,PMC1317065,,,"The serum antibodies to severe acute respiratory syndrome (SARS) coronavirus of 18 SARS patients were checked at 1 month and every 3 months after disease onset. All of them except one, who missed blood sampling at 1 month, tested positive for the immunoglobulin G (IgG) antibody at 1 month. Fifteen out of 17 tested positive for the IgM antibody at 1 month. The serum IgM antibody of most patients became undetectable within 6 months after the onset of SARS. The IgG antibody of all 17 patients, whose serum was checked 1 year after disease onset, remained positive.",,"['Chang, Shan-Chwen', 'Wang, Jann-Tay', 'Huang, Li-Min', 'Chen, Yee-Chun', 'Fang, Chi-Tai', 'Sheng, Wang-Huei', 'Wang, Jiun-Ling', 'Yu, Chong-Jen', 'Yang, Pan-Chyr']",,,,
,PMC,Interferon-α2a is sufficient for promoting dendritic cell immunogenicity,http://dx.doi.org/10.1111/j.1365-2249.2005.02933.x,PMC1809533,,,"Type I interferons (IFNs) are widely used therapeutically. IFN-α2a in particular is used as an antiviral agent, but its immunomodulatory properties are poorly understood. Dendritic cells (DCs) are the only antigen-presenting cells able to prime naive T cells and therefore play a crucial role in initiating the adaptive phase of the immune response. We studied the effects of IFN-α2a on DC maturation and its role in determining Th1/Th2 equilibrium. We found that IFN-α2a induced phenotypic maturation of DCs and increased their allostimulatory capacity. When dendritic cells were stimulated simultaneously by CD40 ligation and IFN-α2a, the production of interleukin (IL)-10 and IL-12 was increased. In contrast, lipopolysaccharide (LPS) stimulation in the presence of IFN-α2a mainly induced IL-10 release. The production of IFN-γ and IL-5 by the responder naive T cells was also amplified in response to IFN-α2a-treated DCs. Furthermore, IL-12 production by IFN-α2a-treated DCs was enhanced further in the presence of anti-IL-10 antibody. Different results were obtained when DCs were treated simultaneously with IFN-α2a and other maturation factors, in particular LPS, and then stimulated by CD40 ligation 36 h later. Under these circumstances, IFN-α2a did not modify the DC phenotype, and the production of IL-10/IL-12 and IFN-γ/IL-5 by DCs and by DC-stimulated naive T cells, respectively, was inhibited compared to the effects on DCs treated with maturation factors alone. Altogether, this work suggests that IFN-α2a in isolation is sufficient to promote DC activation, however, other concomitant events, such as exposure to LPS during a bacterial infection, can inhibit its effects. These results clarify some of the in vivo findings obtained with IFN-α2a and have direct implications for the design of IFN-α-based vaccines for immunotherapy.",,"['Tamir, A', 'Jordan, W J', 'Ritter, M', 'Habib, N', 'Lechler, R I', 'Foster, G R', 'Lombardi, G']",,,,
,PMC,Seroprevalence of SARS coronavirus antibody in household contacts.,http://dx.doi.org/10.1017/S0950268805004541,PMC2870347,,,"Between March and July 2003, 671 cases of severe acute respiratory syndrome (SARS) were diagnosed in Taiwan with a total of 84 fatalities. After the epidemic, a serological survey was conducted involving the asymptomatic household contacts. Household contacts of 13 index patients were enrolled in the study. Contact history and clinical symptoms of the household contacts were recorded by standardized questionnaires. Blood samples of patients and household contacts were collected at least 28 days after symptom onset in the index patients or household exposure in the contacts for SARS-associated coronavirus (SARS-CoV) IgG testing. On the basis of this investigation, 29 persons (25 adults and 4 children) were identified as having had unprotected exposure to the index cases before infection-control practices were implemented. Laboratory evaluation of clinical specimens showed no evidence of transmission of SARS-CoV infection to any contacts. This investigation demonstrated that subclinical transmission among household contacts was low in the described setting.",,"['Lee, C-C', 'Chen, S-Y', 'Chang, I-J', 'Tsai, P-C', 'Lu, T-C', 'Wu, P-L', 'Chen, W-J', 'Huang, L-M', 'Chang, S-C']",,,,
,PMC,Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2,http://dx.doi.org/10.1136/gut.2004.062398,PMC1774784,,,"Background: Angiotensin converting enzyme (ACE) 2 is a recently identified homologue of ACE that may counterregulate the actions of angiotensin (Ang) II by facilitating its breakdown to Ang 1–7. The renin-angiotensin system (RAS) has been implicated in the pathogenesis of cirrhosis but the role of ACE2 in liver disease is not known. Aims: This study examined the effects of liver injury on ACE2 expression and activity in experimental hepatic fibrosis and human cirrhosis, and the effects of Ang 1–7 on vascular tone in cirrhotic rat aorta. Methods: In sham operated and bile duct ligated (BDL) rats, quantitative reverse transcriptase-polymerase chain reaction was used to assess hepatic ACE2 mRNA, and western blotting and immunohistochemistry to quantify and localise ACE2 protein. ACE2 activity was quantified by quenched fluorescent substrate assay. Similar studies were performed in normal human liver and in hepatitis C cirrhosis. Results: ACE2 mRNA was detectable at low levels in rat liver and increased following BDL (363-fold; p<0.01). ACE2 protein increased after BDL (23.5-fold; p<0.05) as did ACE2 activity (fourfold; p<0.05). In human cirrhotic liver, gene (>30-fold), protein expression (97-fold), and activity of ACE2 (2.4 fold) were increased compared with controls (all p<0.01). In healthy livers, ACE2 was confined to endothelial cells, occasional bile ducts, and perivenular hepatocytes but in both BDL and human cirrhosis there was widespread parenchymal expression of ACE2 protein. Exposure of cultured human hepatocytes to hypoxia led to increased ACE2 expression. In preconstricted rat aorta, Ang 1–7 alone did not affect vascular tone but it significantly enhanced acetylcholine mediated vasodilatation in cirrhotic vessels. Conclusions: ACE2 expression is significantly increased in liver injury in both humans and rat, possibly in response to increasing hepatocellular hypoxia, and may modulate RAS activity in cirrhosis.",,"['Paizis, G', 'Tikellis, C', 'Cooper, M E', 'Schembri, J M', 'Lew, R A', 'Smith, A I', 'Shaw, T', 'Warner, F J', 'Zuilli, A', 'Burrell, L M', 'Angus, P W']",,,,
,PMC,In situ data collection and structure refinement from microcapillary protein crystallization,http://dx.doi.org/10.1107/S002188980502649X,PMC1858637,,,"In situ X-ray data collection has the potential to eliminate the challenging task of mounting and cryocooling often fragile protein crystals, reducing a major bottleneck in the structure determination process. An apparatus used to grow protein crystals in capillaries and to compare the background X-ray scattering of the components, including thin-walled glass capillaries against Teflon, and various fluorocarbon oils against each other, is described. Using thaumatin as a test case at 1.8 Å resolution, this study demonstrates that high-resolution electron density maps and refined models can be obtained from in situ diffraction of crystals grown in microcapillaries.",,"['Yadav, Maneesh K.', 'Gerdts, Cory J.', 'Sanishvili, Ruslan', 'Smith, Ward W.', 'Roach, L. Spencer', 'Ismagilov, Rustem F.', 'Kuhn, Peter', 'Stevens, Raymond C.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.79.24.15005-15006.2005,PMC1316047,,,,,,,,,
,PMC,Soluble Receptor-Mediated Targeting of Mouse Hepatitis Coronavirus to the Human Epidermal Growth Factor Receptor,http://dx.doi.org/10.1128/JVI.79.24.15314-15322.2005,PMC1316040,,,"The mouse hepatitis coronavirus (MHV) infects murine cells by binding of its spike (S) protein to murine CEACAM1a. The N-terminal part of this cellular receptor (soR) is sufficient for S binding and for subsequent induction of the conformational changes required for virus-cell membrane fusion. Here we analyzed whether these characteristics can be used to redirect MHV to human cancer cells. To this end, the soR domain was coupled to single-chain monoclonal antibody 425, which is directed against the human epidermal growth factor receptor (EGFR), resulting in a bispecific adapter protein (soR-425). The soR and soR-425 proteins, both produced with the vaccinia virus system, were able to neutralize MHV infection of murine LR7 cells. However, only soR-425 was able to target MHV to human EGFR-expressing cancer cells. Interestingly, the targeted infections induced syncytium formation. Furthermore, the soR-425-mediated infections were blocked by heptad repeat-mimicking peptides, indicating that virus entry requires the regular S protein fusion process. We conclude that the specific spike-binding property of the CEACAM1a N-terminal fragment can be exploited to direct the virus to selected cells by linking it to a moiety able to bind a receptor on those cells. This approach might be useful in the development of tumor-targeted coronaviruses.",,"['Würdinger, T.', 'Verheije, M. H.', 'Broen, K.', 'Bosch, B. J.', 'Haijema, B. J.', 'de Haan, C. A. M.', 'van Beusechem, V. W.', 'Gerritsen, W. R.', 'Rottier, P. J. M.']",,,,
,PMC,The Papain-Like Protease from the Severe Acute Respiratory Syndrome Coronavirus Is a Deubiquitinating Enzyme,http://dx.doi.org/10.1128/JVI.79.24.15199-15208.2005,PMC1316033,,,"The severe acute respiratory syndrome coronavirus papain-like protease (SARS-CoV PLpro) is involved in the processing of the viral polyprotein and, thereby, contributes to the biogenesis of the virus replication complex. Structural bioinformatics has revealed a relationship for the SARS-CoV PLpro to herpesvirus-associated ubiquitin-specific protease (HAUSP), a ubiquitin-specific protease, indicating potential deubiquitinating activity in addition to its function in polyprotein processing (T. Sulea, H. A. Lindner, E. O. Purisima, and R. Menard, J. Virol. 79:4550-4551, 2005). In order to confirm this prediction, we overexpressed and purified SARS-CoV PLpro (amino acids [aa]1507 to 1858) from Escherichia coli. The purified enzyme hydrolyzed ubiquitin-7-amino-4-methylcoumarin (Ub-AMC), a general deubiquitinating enzyme substrate, with a catalytic efficiency of 13,100 M(−1)s(−1), 220-fold more efficiently than the small synthetic peptide substrate Z-LRGG-AMC, which incorporates the C-terminal four residues of ubiquitin. In addition, SARS-CoV PLpro was inhibited by the specific deubiquitinating enzyme inhibitor ubiquitin aldehyde, with an inhibition constant of 210 nM. The purified SARS-CoV PLpro disassembles branched polyubiquitin chains with lengths of two to seven (Ub2-7) or four (Ub4) units, which involves isopeptide bond cleavage. SARS-CoV PLpro processing activity was also detected against a protein fused to the C terminus of the ubiquitin-like modifier ISG15, both in vitro using the purified enzyme and in HeLa cells by coexpression with SARS-CoV PLpro (aa 1198 to 2009). These results clearly establish that SARS-CoV PLpro is a deubiquitinating enzyme, thereby confirming our earlier prediction. This unexpected activity for a coronavirus papain-like protease suggests a novel viral strategy to modulate the host cell ubiquitination machinery to its advantage.",,"['Lindner, Holger A.', 'Fotouhi-Ardakani, Nasser', 'Lytvyn, Viktoria', 'Lachance, Paule', 'Sulea, Traian', 'Ménard, Robert']",,,,
,PMC,The Papain-Like Protease of Severe Acute Respiratory Syndrome Coronavirus Has Deubiquitinating Activity,http://dx.doi.org/10.1128/JVI.79.24.15189-15198.2005,PMC1316023,,,"Replication of the genomic RNA of severe acute respiratory syndrome coronavirus (SARS-CoV) is mediated by replicase polyproteins that are processed by two viral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro). Previously, we showed that SARS-CoV PLpro processes the replicase polyprotein at three conserved cleavage sites. Here, we report the identification and characterization of a 316-amino-acid catalytic core domain of PLpro that can efficiently cleave replicase substrates in trans-cleavage assays and peptide substrates in fluorescent resonance energy transfer-based protease assays. We performed bioinformatics analysis on 16 papain-like protease domains from nine different coronaviruses and identified a putative catalytic triad (Cys1651-His1812-Asp1826) and zinc-binding site. Mutagenesis studies revealed that Asp1826 and the four cysteine residues involved in zinc binding are essential for SARS-CoV PLpro activity. Molecular modeling of SARS-CoV PLpro suggested that this catalytic core may also have deubiquitinating activity. We tested this hypothesis by measuring the deubiquitinating activity of PLpro by two independent assays. SARS CoV-PLpro hydrolyzed both diubiquitin and ubiquitin-7-amino-4-methylcoumarin (AMC) substrates, and hydrolysis of ubiquitin-AMC is approximately 180-fold more efficient than hydrolysis of a peptide substrate that mimics the PLpro replicase recognition sequence. To investigate the critical determinants recognized by PLpro, we performed site-directed mutagenesis on the P6 to P2′ residues at each of the three PLpro cleavage sites. We found that PLpro recognizes the consensus cleavage sequence LXGG, which is also the consensus sequence recognized by cellular deubiquitinating enzymes. This similarity in the substrate recognition sites should be considered during the development of SARS-CoV PLpro inhibitors.",,"['Barretto, Naina', 'Jukneliene, Dalia', 'Ratia, Kiira', 'Chen, Zhongbin', 'Mesecar, Andrew D.', 'Baker, Susan C.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Infection of Human Ciliated Airway Epithelia: Role of Ciliated Cells in Viral Spread in the Conducting Airways of the Lungs,http://dx.doi.org/10.1128/JVI.79.24.15511-15524.2005,PMC1316022,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 as an important cause of severe lower respiratory tract infection in humans, and in vitro models of the lung are needed to elucidate cellular targets and the consequences of viral infection. The SARS-CoV receptor, human angiotensin 1-converting enzyme 2 (hACE2), was detected in ciliated airway epithelial cells of human airway tissues derived from nasal or tracheobronchial regions, suggesting that SARS-CoV may infect the proximal airways. To assess infectivity in an in vitro model of human ciliated airway epithelia (HAE) derived from nasal and tracheobronchial airway regions, we generated recombinant SARS-CoV by deletion of open reading frame 7a/7b (ORF7a/7b) and insertion of the green fluorescent protein (GFP), resulting in SARS-CoV GFP. SARS-CoV GFP replicated to titers similar to those of wild-type viruses in cell lines. SARS-CoV specifically infected HAE via the apical surface and replicated to titers of 10(7) PFU/ml by 48 h postinfection. Polyclonal antisera directed against hACE2 blocked virus infection and replication, suggesting that hACE2 is the primary receptor for SARS-CoV infection of HAE. SARS-CoV structural proteins and virions localized to ciliated epithelial cells. Infection was highly cytolytic, as infected ciliated cells were necrotic and shed over time onto the luminal surface of the epithelium. SARS-CoV GFP also replicated to a lesser extent in ciliated cell cultures derived from hamster or rhesus monkey airways. Efficient SARS-CoV infection of ciliated cells in HAE provides a useful in vitro model of human lung origin to study characteristics of SARS-CoV replication and pathogenesis.",,"['Sims, Amy C.', 'Baric, Ralph S.', 'Yount, Boyd', 'Burkett, Susan E.', 'Collins, Peter L.', 'Pickles, Raymond J.']",,,,
,PMC,Expression of Hemagglutinin Esterase Protein from Recombinant Mouse Hepatitis Virus Enhances Neurovirulence,http://dx.doi.org/10.1128/JVI.79.24.15064-15073.2005,PMC1316009,,,"Murine hepatitis virus (MHV) infection provides a model system for the study of hepatitis, acute encephalitis, and chronic demyelinating disease. The spike glycoprotein, S, which mediates receptor binding and membrane fusion, plays a critical role in MHV pathogenesis. However, viral proteins other than S also contribute to pathogenicity. The JHM strain of MHV is highly neurovirulent and expresses a second spike glycoprotein, the hemagglutinin esterase (HE), which is not produced by MHV-A59, a hepatotropic but only mildly neurovirulent strain. To investigate a possible role for HE in MHV-induced neurovirulence, isogenic recombinant MHV-A59 viruses were generated that produced either (i) the wild-type protein, (ii) an enzymatically inactive HE protein, or (iii) no HE at all (A. Lissenberg, M. M. Vrolijk, A. L. W. van Vliet, M. A. Langereis, J. D. F. de Groot-Mijnes, P. J. M. Rottier, and R. J. de Groot, J. Virol. 79:15054-15063, 2005 [accompanying paper]). A second, mirror set of recombinant viruses was constructed in which, in addition, the MHV-A59 S gene had been replaced with that from MHV-JHM. The expression of HE in combination with A59 S did not affect the tropism, pathogenicity, or spread of the virus in vivo. However, in combination with JHM S, the expression of HE, regardless of whether it retained esterase activity or not, resulted in increased viral spread within the central nervous system and in increased neurovirulence. Our findings suggest that the properties of S receptor utilization and/or fusogenicity mainly determine organ and host cell tropism but that HE enhances the efficiency of infection and promotes viral dissemination, at least in some tissues, presumably by serving as a second receptor-binding protein.",,"['Kazi, Lubna', 'Lissenberg, Arjen', 'Watson, Richard', 'de Groot, Raoul J.', 'Weiss, Susan R.']",,,,
,PMC,Luxury at a Cost? Recombinant Mouse Hepatitis Viruses Expressing the Accessory Hemagglutinin Esterase Protein Display Reduced Fitness In Vitro,http://dx.doi.org/10.1128/JVI.79.24.15054-15063.2005,PMC1316008,,,"Group 2 coronaviruses encode an accessory envelope glycoprotein species, the hemagglutinin esterase (HE), which possesses sialate-O-acetylesterase activity and which, presumably, promotes virus spread and entry in vivo by facilitating reversible virion attachment to O-acetylated sialic acids. While HE may provide a strong selective advantage during natural infection, many laboratory strains of mouse hepatitis virus (MHV) fail to produce the protein. Apparently, their HE genes were inactivated during cell culture adaptation. For this report, we have studied the molecular basis of this phenomenon. By using targeted RNA recombination, we generated isogenic recombinant MHVs which differ exclusively in their expression of HE and produce either the wild-type protein (HE(+)), an enzymatically inactive HE protein (HE(0)), or no HE at all. HE expression or the lack thereof did not lead to gross differences in in vitro growth properties. Yet the expression of HE was rapidly lost during serial cell culture passaging. Competition experiments with mixed infections revealed that this was not due to the enzymatic activity: MHVs expressing HE(+) or HE(0) propagated with equal efficiencies. During the propagation of recombinant MHV-HE(+), two types of spontaneous mutants accumulated. One produced an anchorless HE, while the other had a Gly-to-Trp substitution at the predicted C-terminal residue of the HE signal peptide. Neither mutant incorporated HE into virion particles, suggesting that wild-type HE reduces the in vitro propagation efficiency, either at the assembly stage or at a postassembly level. Our findings demonstrate that the expression of “luxury” proteins may come at a fitness penalty. Apparently, under natural conditions the costs of maintaining HE are outweighed by the benefits.",,"['Lissenberg, A.', 'Vrolijk, M. M.', 'van Vliet, A. L. W.', 'Langereis, M. A.', 'de Groot-Mijnes, J. D. F.', 'Rottier, P. J. M.', 'de Groot, R. J.']",,,,
,PMC,A Point Mutation within the Replicase Gene Differentially Affects Coronavirus Genome versus Minigenome Replication,http://dx.doi.org/10.1128/JVI.79.24.15016-15026.2005,PMC1316003,,,"During the construction of the transmissible gastroenteritis virus (TGEV) full-length cDNA clone, a point mutation at position 637 that was present in the defective minigenome DI-C was maintained as a genetic marker. Sequence analysis of the recovered viruses showed a reversion at this position to the original virus sequence. The effect of point mutations at nucleotide 637 was analyzed by reverse genetics using a TGEV full-length cDNA clone and cDNAs from TGEV-derived minigenomes. The replacement of nucleotide 637 of TGEV genome by a T, as in the DI-C sequence, or an A severely affected virus recovery from the cDNA, yielding mutant viruses with low titers and small plaques compared to those of the wild type. In contrast, T or A at position 637 was required for minigenome rescue in trans by the helper virus. No relationship between these observations and RNA secondary-structure predictions was found, indicating that mutations at nucleotide 637 most likely had an effect at the protein level. Nucleotide 637 occupies the second codon position at amino acid 108 of the pp1a polyprotein. This position is predicted to map in the N-terminal polyprotein papain-like proteinase (PLP-1) cleavage site at the p9/p87 junction. Replacement of G-637 by A, which causes a drastic amino acid change (Gly to Asp) at position 108, affected PLP-1-mediated cleavage in vitro. A correlation was found between predicted cleaving and noncleaving mutations and efficient virus rescue from cDNA and minigenome amplification, respectively.",,"['Galán, Carmen', 'Enjuanes, Luis', 'Almazán, Fernando']",,,,
,PMC,Effect of Mutations in the Mouse Hepatitis Virus 3′(+)42 Protein Binding Element on RNA Replication,http://dx.doi.org/10.1128/JVI.79.23.14570-14585.2005,PMC1287598,,,"The mouse hepatitis virus (MHV) genome's 3′ untranslated region contains cis-acting sequences necessary for replication. Studies of MHV and other coronaviruses have indicated a role for RNA secondary and tertiary elements in replication. Previous work in our laboratory has identified four proteins which form ribonucleoprotein complexes with the 3′-terminal 42 nucleotides [3′(+)42] of the MHV genome. Defective interfering (DI) RNA replication assays have demonstrated a role for the 3′(+)42 host protein binding element in the MHV life cycle. Using gel mobility shift RNase T(1) protection assays and secondary structure modeling, we have characterized a possible role for RNA secondary structure in host protein binding to the 3′-terminal 42-nucleotide element. Additionally we have identified a role for the 3′-terminal 42-nucleotide host protein binding element in RNA replication and transcription using DI RNA replication assays and targeted recombination and by directly constructing mutants in this protein binding element using a recently described MHV reverse genetic system. DI RNA replication assays demonstrated that mutations in the 3′(+)42 host protein binding element had a deleterious effect on the accumulation of DI RNA. When the identical mutations were directly inserted into the MHV genome, most mutant genomes were viable but formed smaller plaques than the wild-type parent virus. One mutant was not viable. This mutant directed the synthesis of genome-sized negative-sense RNA approximately as efficiently as the wild type did but had a defect in subgenomic mRNA synthesis. These results point to a potential role for sequences at the extreme 3′ end of the MHV genome in subgenomic RNA synthesis.",,"['Johnson, Reed F.', 'Feng, Min', 'Liu, Pinghua', 'Millership, Jason J.', 'Yount, Boyd', 'Baric, Ralph S.', 'Leibowitz, Julian L.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.79.23.14471-14472.2005,PMC1287597,,,,,,,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Group-Specific Open Reading Frames Encode Nonessential Functions for Replication in Cell Cultures and Mice,http://dx.doi.org/10.1128/JVI.79.23.14909-14922.2005,PMC1287583,,,"SARS coronavirus (SARS-CoV) encodes several unique group-specific open reading frames (ORFs) relative to other known coronaviruses. To determine the significance of the SARS-CoV group-specific ORFs in virus replication in vitro and in mice, we systematically deleted five of the eight group-specific ORFs, ORF3a, OF3b, ORF6, ORF7a, and ORF7b, and characterized recombinant virus replication and gene expression in vitro. Deletion of the group-specific ORFs of SARS-CoV, either alone or in various combinations, did not dramatically influence replication efficiency in cell culture or in the levels of viral RNA synthesis. The greatest reduction in virus growth was noted following ORF3a deletion. SARS-CoV spike (S) glycoprotein does not encode a rough endoplasmic reticulum (rER)/Golgi retention signal, and it has been suggested that ORF3a interacts with and targets S glycoprotein retention in the rER/Golgi apparatus. Deletion of ORF3a did not alter subcellular localization of the S glycoprotein from distinct punctuate localization in the rER/Golgi apparatus. These data suggest that ORF3a plays little role in the targeting of S localization in the rER/Golgi apparatus. In addition, insertion of the 29-bp deletion fusing ORF8a/b into the single ORF8, noted in early-stage SARS-CoV human and civet cat isolates, had little if any impact on in vitro growth or RNA synthesis. All recombinant viruses replicated to wild-type levels in the murine model, suggesting that either the group-specific ORFs play little role in in vivo replication efficiency or that the mouse model is not of sufficient quality for discerning the role of the group-specific ORFs in disease origin and development.",,"['Yount, Boyd', 'Roberts, Rhonda S.', 'Sims, Amy C.', 'Deming, Damon', 'Frieman, Matthew B.', 'Sparks, Jennifer', 'Denison, Mark R.', 'Davis, Nancy', 'Baric, Ralph S.']",,,,
,PMC,Central Nervous System Pathology Caused by Autoreactive CD8(+) T-Cell Clones following Virus Infection,http://dx.doi.org/10.1128/JVI.79.23.14640-14646.2005,PMC1287580,,,"Theiler's murine encephalomyelitis virus (TMEV) causes a demyelinating disease in infected mice which has similarities to multiple sclerosis. Spleen cells from TMEV-infected SJL/J mice stimulated with antigen-presenting cells infected with TMEV resulted in a population of autoreactive CD8(+) cytotoxic T cells that kill uninfected syngeneic cells. We established CD8(+) T cell clones that could kill both TMEV-infected and uninfected syngeneic targets, although infected target cells were killed more efficiently. The CD8(+) T-cell clones produced gamma interferon when incubated with either infected or uninfected syngeneic target cells. Intracerebral injection of the clones into naïve mice induced degeneration, not only in the brain, but also in the spinal cord. This suggests that CD8(+) Tc1 cells could play a pathogenic role in central nervous system inflammation.",,"['Tsunoda, Ikuo', 'Kuang, Li-Qing', 'Kobayashi-Warren, Mikako', 'Fujinami, Robert S.']",,,,
,PMC,ACE2 Receptor Expression and Severe Acute Respiratory Syndrome Coronavirus Infection Depend on Differentiation of Human Airway  Epithelia,http://dx.doi.org/10.1128/JVI.79.23.14614-14621.2005,PMC1287568,,,"Studies of patients with severe acute respiratory syndrome (SARS) demonstrate that the respiratory tract is a major site of SARS-coronavirus (CoV) infection and disease morbidity. We studied host-pathogen interactions using native lung tissue and a model of well-differentiated cultures of primary human airway epithelia. Angiotensin converting enzyme 2 (ACE2), the receptor for both the SARS-CoV and the related human respiratory coronavirus NL63, was expressed in human airway epithelia as well as lung parenchyma. As assessed by immunofluorescence staining and membrane biotinylation, ACE2 protein was more abundantly expressed on the apical than the basolateral surface of polarized airway epithelia. Interestingly, ACE2 expression positively correlated with the differentiation state of epithelia. Undifferentiated cells expressing little ACE2 were poorly infected with SARS-CoV, while well-differentiated cells expressing more ACE2 were readily infected. Expression of ACE2 in poorly differentiated epithelia facilitated SARS spike (S) protein-pseudotyped virus entry. Consistent with the expression pattern of ACE2, the entry of SARS-CoV or a lentivirus pseudotyped with SARS-CoV S protein in differentiated epithelia was more efficient when applied to the apical surface. Furthermore, SARS-CoV replicated in polarized epithelia and preferentially exited via the apical surface. The results indicate that infection of human airway epithelia by SARS coronavirus correlates with the state of cell differentiation and ACE2 expression and localization. These findings have implications for understanding disease pathogenesis associated with SARS-CoV and NL63 infections.",,"['Jia, Hong Peng', 'Look, Dwight C.', 'Shi, Lei', 'Hickey, Melissa', 'Pewe, Lecia', 'Netland, Jason', 'Farzan, Michael', 'Wohlford-Lenane, Christine', 'Perlman, Stanley', 'McCray, Paul B.']",,,,
,PMC,The AAUAAA Motif of Bamboo Mosaic Virus RNA Is Involved in Minus-Strand RNA Synthesis and Plus-Strand RNA Polyadenylation,http://dx.doi.org/10.1128/JVI.79.23.14555-14561.2005,PMC1287560,,,"Bamboo mosaic virus (BaMV) has a single-stranded positive-sense RNA genome with a 5′-cap structure and a 3′ poly(A) tail. Deleting the internal loop that contains the putative polyadenylation signal (AAUAAA) in the 3′ untranslated region (UTR) of BaMV genomic RNA appeared to diminish coat protein accumulation to 2% (C. P. Cheng and C. H. Tsai, J. Mol. Biol. 288:555-565, 1999). To investigate the function of the AAUAAA motif, mutations were introduced into an infectious BaMV cDNA at each residue except the first nucleotide. After transfection of Nicotiana benthamiana protoplasts with RNA transcript, the accumulations of viral coat protein and RNAs were determined. Based on the results, three different categories could be deduced for the mutants. Category 1 includes two mutants expressing levels of the viral products similar to those of the wild-type virus. Six mutations in category 2 led to decreased to similar levels of both minus-strand and genomic RNAs. Category 3 includes the remaining seven mutations that also bring about decreases in both minus- and plus-strand RNA levels, with more significant effects on genomic RNA accumulation. Mutant transcripts from each category were used to infect N. benthamiana plants, from which viral particles were isolated. The genomic RNAs of mutants in category 3 were found to have shorter poly(A) tails. Taken together, the results suggest that the AAUAAA motif in the 3′ UTR of BaMV genomic RNA is involved not only in the formation of the poly(A) tail of the plus-strand RNA, but also in minus-strand RNA synthesis.",,"['Chen, I-Hsuan', 'Chou, Wen-Jen', 'Lee, Pei-Yu', 'Hsu, Yau-Heiu', 'Tsai, Ching-Hsiu']",,,,
,PMC,Coronavirus Pathogenesis and the Emerging Pathogen Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/MMBR.69.4.635-664.2005,PMC1306801,,,"Coronaviruses are a family of enveloped, single-stranded, positive-strand RNA viruses classified within the Nidovirales order. This coronavirus family consists of pathogens of many animal species and of humans, including the recently isolated severe acute respiratory syndrome coronavirus (SARS-CoV). This review is divided into two main parts; the first concerns the animal coronaviruses and their pathogenesis, with an emphasis on the functions of individual viral genes, and the second discusses the newly described human emerging pathogen, SARS-CoV. The coronavirus part covers (i) a description of a group of coronaviruses and the diseases they cause, including the prototype coronavirus, murine hepatitis virus, which is one of the recognized animal models for multiple sclerosis, as well as viruses of veterinary importance that infect the pig, chicken, and cat and a summary of the human viruses; (ii) a short summary of the replication cycle of coronaviruses in cell culture; (iii) the development and application of reverse genetics systems; and (iv) the roles of individual coronavirus proteins in replication and pathogenesis. The SARS-CoV part covers the pathogenesis of SARS, the developing animal models for infection, and the progress in vaccine development and antiviral therapies. The data gathered on the animal coronaviruses continue to be helpful in understanding SARS-CoV.",,"['Weiss, Susan R.', 'Navas-Martin, Sonia']",,,,
,PMC,Poster presentations,,PMC1766041,,,,,,,,,
,PMC,Fibrinogen-like protein 2 fibroleukin expression and its correlation with disease progression in murine hepatitis virus type 3-induced fulminant hepatitis and in patients with severe viral hepatitis B,http://dx.doi.org/10.3748/wjg.v11.i44.6936,PMC4717034,,,"AIM: To evaluate the expression of fibrinogen-like protein 2 (fgl2) and its correlation with disease progression in both mice and patients with severe viral hepatitis. METHODS: Balb/cJ or A/J mice were infected intraperitoneally (ip) with 100 PFU of murine hepatitis virus type 3 (MHV-3), liver and serum were harvested at 24, 48, and 72 h post infection for further use. Liver tissues were obtained from 23 patients with severe acute chronic (AOC) hepatitis B and 13 patients with mild chronic hepatitis B. Fourteen patients with mild chronic hepatitis B with cirrhosis and 4 liver donors served as normal controls. In addition, peripheral blood mononuclear cells (PBMC) were isolated from 30 patients (unpaired) with severe AOC hepatitis B and 10 healthy volunteers as controls. Procoagulant activity representing functional prothrombinase activity in PBMC and white blood cells was also assayed. A polyclonal antibody against fgl2 was used to detect the expression of both mouse and human fgl2 protein in liver samples as well as in PBMC by immunohistochemistry staining in a separate set of studies. Alanine aminotransferase (ALT) and total bilirubin (TBil) in serum were measured to assess the severity of liver injury. RESULTS: Histological changes were found in liver sections 12-24 h post MHV-3 infection in Balb/cJ mice. In association with changes in liver histology, marked elevations in serum ALT and TBil were observed. Mouse fgl2 (mfgl2) protein was detected in the endothelium of intrahepatic veins and hepatic sinusoids within the liver 24 h after MHV-3 infection. Liver tissues from the patients with severe AOC hepatitis B had classical pathological features of acute necroinflammation. Human fgl2 (hfgl2) was detected in 21 of 23 patients (91.30%) with severe AOC hepatitis B, while only 1 of 13 patients (7.69%) with mild chronic hepatitis B and cirrhosis had hfgl2 mRNA or protein expression. Twenty-eight of thirty patients (93.33%) with severe AOC hepatitis B and 1 of 10 with mild chronic hepatitis B had detectable hfgl2 expression in PBMC. No hfgl2 expression was found either in the liver tissue or in the PBMC from normal donors. There was a positive correlation between hfgl2 expression and the severity of the liver disease as indicated by the levels of TBil. PCA significantly increased in PBMC in patients with severe AOC hepatitis B. CONCLUSION: The molecular and cellular results reported here in both mice and patients with severe viral hepatitis suggest that virus-induced hfgl2 prothrombinase/fibroleukin expression and the coagulation activity associated with the encoded fgl2 protein play a pivotal role in initiating severe hepatitis. The measurement of hfgl2/fibroleukin expression in PBMC may serve as a useful marker to monitor the severity of AOC hepatitis B and a target for therapeutic intervention.",,"['Zhu, Chuan-Long', 'Yan, Wei-Ming', 'Zhu, Fan', 'Zhu, Yong-Fen', 'Xi, Dong', 'Tian, De-Ying', 'Levy, Gary', 'Luo, Xiao-Ping', 'Ning, Qin']",,,,
,PMC,Entry screening for severe acute respiratory syndrome (SARS) or influenza: policy evaluation,http://dx.doi.org/10.1136/bmj.38573.696100.3A,PMC1289362,,,,,"['Pitman, R J', 'Cooper, B S', 'Trotter, C L', 'Gay, N J', 'Edmunds, W J']",,,,
,PMC,The Monster at Our Door: The Global Threat of Avian Flu,,PMC1289342,,,,,"Watts, Geoff",,,,
,PMC,The animal story,,PMC1289332,,,The UN Food and Agriculture Organisation's global rinderpest eradication programme (GREP)—the first and only attempt to eradicate an animal pathogen—provides several learning points from the veterinary perspective,,"Roeder, Peter L",,,,
,PMC,The human story,,PMC1289331,,,"Eradicating human pathogens is a young science, and there is still much to learn about its role in controlling existing and emerging diseases",,"['Aylward, R Bruce', 'Birmingham, Maureen']",,,,
,PMC,Zoonotic potential of emerging animal diseases,,PMC1289330,,,,,"['Wong, Samson S Y', 'Yuen, K Y']",,,,
,PMC,Vaccinating poultry against avian flu is contributing to spread,,PMC1289310,,,,,"Parry, Jane",,,,
,PMC,UK government collaborations to manage threats to animal and human health: The chief veterinary and chief medical officers are working closely together on bird flu and other zoonoses,,PMC1289305,,,,,"['Reynolds, Debby', 'Donaldson, Liam']",,,,
,PMC,A walk on the wild side—emerging wildlife diseases: They increasingly threaten human and animal health,,PMC1289304,,,,,"Cunningham, Andrew A",,,,
,PMC,Cross-reactive influenza virus–specific CD8+ T cells contribute to lymphoproliferation  in Epstein-Barr virus–associated  infectious mononucleosis,http://dx.doi.org/10.1172/JCI25078,PMC1288832,,,"The marked proliferation of activated CD8(+) T cells is pathognomonic of EBV-associated infectious mononucleosis (IM), common in young adults. Since the diversity and size of the memory CD8(+) T cell population increase with age, we questioned whether IM was mediated by the reactivation of memory CD8(+) T cells specific to previously encountered pathogens but cross-reactive with EBV. Of 8 HLA-A2(+) IM patients, 5 had activated T cells specific to another common virus, as evidenced by a significantly higher number of peripheral blood influenza A virus M1(58–66)–specific T cells compared with healthy immune donors. Two patients with an augmented M1 response had tetramer-defined cross-reactive cells recognizing influenza M1 and EBV-BMLF1(280–288), which accounted for up to one-third of their BMLF1-specific population and likely contributed to a skewed M1-specific T cell receptor repertoire. These epitopes, with only 33% sequence similarity, mediated differential effects on the function of the cross-reactive T cells, which may contribute to alterations in disease outcome. EBV could potentially encode an extensive pool of T cell epitopes that activate other cross-reactive memory T cells. Our results support the concept that cross-reactive memory CD8(+) T cells activated by EBV contribute to the characteristic lymphoproliferation of IM.",,"['Clute, Shalyn C.', 'Watkin, Levi B.', 'Cornberg, Markus', 'Naumov, Yuri N.', 'Sullivan, John L.', 'Luzuriaga, Katherine', 'Welsh, Raymond M.', 'Selin, Liisa K.']",,,,
,PMC,The US Public Broadcasting System and Time Magazine take on global health,,PMC1283291,,,"A week of events including the television series RX for Survival: A Global Health Challenge, broadcast on PBS from 1 to 3 November and available on VHS and DVD www.pbs.org/wgbh/rxforsurvival/index.html Rating: ★★★",,"Novotny, Thomas E",,,,
,PMC,Global Fund withdraws grants to Myanmar.,,PMC2626419,,,,,"Parry, Jane",,,,
,PMC,Emerging diseases fuel health screening.,,PMC2626416,,,,,"Khanal, Prakash",,,,
,PMC,The broad anti-viral agent glycyrrhizin directly modulates the fluidity of plasma membrane and HIV-1 envelope,http://dx.doi.org/10.1042/BJ20051069,PMC1317678,,,"Cell entry of enveloped viruses requires a wide-fusion-pore mechanism, involving clustering of fusion-activated proteins and fluidization of the plasma membrane and viral envelope. In the present study, GL (glycyrrhizin) is reported to lower membrane fluidity, thus suppressing infection by HIV, influenza A virus and vesicular stomatitis virus, but not by poliovirus. GL-treated HIV-1 particles showed reduced infectivity. GL also inhibited cell-to-cell fusion induced by HIV-1 and HTLV-I (human T-cell leukaemia virus type I). However, when cells treated with 1 mg/ml GL were placed in GL-free medium, they showed increased susceptibility to HIV-1 infection and HTLV-I fusion due to enhancement of membrane fluidity. The membrane dependence of GL and GL removal experiments suggest that GL does affect the cell entry of viruses. HIVs with more gp120 were less dependent on temperature and less sensitive to GL treatment than those with less gp120, indicating that the existence of more gp120 molecules resulted in a higher probability of forming a cluster of fusion-activated proteins.",,"Harada, Shinji",,,,
,PMC,Bcl-xL inhibits T-cell apoptosis induced by expression of SARS coronavirus E protein in the absence of growth factors,http://dx.doi.org/10.1042/BJ20050698,PMC1317672,,,"One of the hallmark findings in patients suffering from SARS (severe acute respiratory syndrome) is lymphopenia, which is the result of massive lymphocyte death. SARS-CoV (SARS coronavirus), a novel coronavirus that has been etiologically associated with SARS cases, is homologous with MHV (murine hepatitis coronavirus), and MHV small envelope E protein is capable of inducing apoptosis. We hypothesized that SARS-CoV encodes a small envelope E protein that is homologous with MHV E protein, thus inducing T-cell apoptosis. To test this hypothesis, a cDNA encoding SARS-CoV E protein was created using whole gene synthesis. Our results showed that SARS-CoV E protein induced apoptosis in the transfected Jurkat T-cells, which was amplified to higher apoptosis rates in the absence of growth factors. However, apoptosis was inhibited by overexpressed antiapoptotic protein Bcl-xL. Moreover, we found that SARS-CoV E protein interacted with Bcl-xL in vitro and endogenous Bcl-xL in vivo and that Bcl-xL interaction with SARS-CoV E protein was mediated by BH3 (Bcl-2 homology domain 3) of Bcl-xL. Finally, we identified a novel BH3-like region located in the C-terminal cytosolic domain of SARS-CoV E protein, which mediates its binding to Bcl-xL. These results demonstrate, for the first time, a novel molecular mechanism of T-cell apoptosis that contributes to the SARS-CoV-induced lymphopenia observed in most SARS patients.",,"['Yang, Yu', 'Xiong, Zeyu', 'Zhang, Sheng', 'Yan, Yan', 'Nguyen, Justin', 'Ng, Bernard', 'Lu, Huifang', 'Brendese, John', 'Yang, Fan', 'Wang, Hong', 'Yang, Xiao-Feng']",,,,
,PMC,Influenza pandemics and avian flu,,PMC1283192,,,"Douglas Fleming is general practitioner in a large suburban practice in Birmingham. In this article he seeks to clarify clinical issues relating to potential pandemics of influenza, including avian influenza",,"Fleming, Douglas",,,,
,PMC,Public Health Approach to Emerging Infections Among Pregnant Women,http://dx.doi.org/10.2105/AJPH.2004.054957,PMC1449464,,,"As public health professionals respond to emerging infections, particular attention needs to be paid to pregnant women and their offspring. Pregnant women might be more susceptible to, or more severely affected by, emerging infections. The effects of a new maternal infection on the embryo or fetus are difficult to predict. Some medications recommended for prophylaxis or treatment could harm the embryo or fetus. We discuss the challenges of responding to emerging infections among pregnant women, and we propose strategies for overcoming these challenges.",,"['Rasmussen, Sonja A.', 'Hayes, Edward B.']",,,,
,PMC,Severe acute respiratory syndrome (SARS) in neonates and children,http://dx.doi.org/10.1136/adc.2005.075309,PMC1721969,,,,,"['Li, A', 'Ng, P']",,,,
,PMC,"Serological Responses in Patients with Severe Acute Respiratory Syndrome Coronavirus Infection and Cross-Reactivity with Human Coronaviruses 229E, OC43, and NL63",http://dx.doi.org/10.1128/CDLI.12.11.1317-1321.2005,PMC1287763,,,"The serological response profile of severe acute respiratory syndrome (SARS) coronavirus (CoV) infection was defined by neutralization tests and subclass-specific immunofluorescent (IF) tests using serial sera from 20 patients. SARS CoV total immunoglobulin (Ig) (IgG, IgA, and IgM [IgGAM]) was the first antibody to be detectable. There was no difference in time to seroconversion between the patients who survived (n = 14) and those who died (n = 6). Although SARS CoV IgM was still detectable by IF tests with 8 of 11 patients at 7 months postinfection, the geometric mean titers dropped from 282 at 1 month postinfection to 19 at 7 months (P = 0.001). In contrast, neutralizing antibody and SARS CoV IgGAM and IgG antibody titers remained stable over this period. The SARS CoV antibody response was sometimes associated with an increase in preexisting IF IgG antibody titers for human coronaviruses OC43, 229E, and NL63. There was no change in IF IgG titer for virus capsid antigen from the herpesvirus that was used as an unrelated control, Epstein-Barr virus. In contrast, patients who had OC43 infections, and probably also 229E infections, without prior exposure to SARS CoV had increases of antibodies specific for the infecting virus but not for SARS CoV. There is a need for awareness of cross-reactive antibody responses between coronaviruses when interpreting IF serology.",,"['Chan, K. H.', 'Cheng, V. C. C.', 'Woo, P. C. Y.', 'Lau, S. K. P.', 'Poon, L. L. M.', 'Guan, Y.', 'Seto, W. H.', 'Yuen, K. Y.', 'Peiris, J. S. M.']",,,,
,PMC,Lack of Correlation of Vaginal Impedance Measurements with Hormone Levels in the Rat,,PMC1403319,,,"Hormone levels vary in female rats depending on estrous cycle stage. Vaginal cytology is a reliable method of staging female rats, but vaginal impedance offers an alternative depending on application. We sought to correlate vaginal impedance in cycling female rats with hormone levels. Vaginal cytology was the standard for comparison and verification of estrous cycle stage. Female rats (n = 41) were evaluated twice daily for 15 days via vaginal cytology and impedance to evaluate two or three estrous cycles per rat. During the last 5 days of the study, selected anesthetized sampling groups (n = 3 or 4 rats per group) were bled terminally at each time point to allow hormone determinations concurrently with vaginal cytology and impedance. Rats with abnormal vaginal smears or discharges (n = 5) were evaluated for reproductive tract histology. Rats classified in estrus by vaginal cytology had significantly higher vaginal impedance values than did nonestrus rats, but vaginal impedance and estrous cycle stage as determined by vaginal cytology did not correlate. Because of small sampling size in nonproestrus groups, correlation between vaginal impedance and hormone levels was evaluated only in proestrus rats (n = 22) and was nonsignificant. No correlation occurred between vaginal impedance and hormone levels in unstaged rats (n = 41). Two animals evaluated for reproductive tract histology showed evidence of pseudopregnancy. Vaginal impedance may be useful in distinguishing estrus from nonestrus rats but may be limited for chronic estrous cycle monitoring because of the possible risk of inducing pseudo pregnancy.",,"['SINGLETARY, SYLVIA J.', 'KIRSCH, ALAN J.', 'WATSON, JULIE', 'KARIM, BAKTIAR O.', 'HUSO, DAVID L.', 'HURN, PATRICIA D.', 'MURPHY, STEPHANIE J.']",,,,
,PMC,Expression Library Immunization: a Road Map for Discovery of Vaccines against Infectious Diseases,http://dx.doi.org/10.1128/IAI.73.11.7089-7098.2005,PMC1273844,,,,,"['Talaat, Adel M.', 'Stemke-Hale, Katherine']",,,,
,PMC,"Development of One-Step, Real-Time, Quantitative Reverse Transcriptase PCR Assays for Absolute Quantitation of Human Coronaviruses OC43 and 229E",http://dx.doi.org/10.1128/JCM.43.11.5452-5456.2005,PMC1287813,,,"The clinical significance of human coronaviruses in more severe respiratory illnesses has recently been shown to be higher than was previously assumed. Rapid and reliable diagnosis of human coronavirus infections therefore becomes indispensable in a routine clinical setting. In this study, we present a very sensitive and specific TaqMan-based, real-time quantitative reverse transcriptase PCR (qRT-PCR) for the rapid detection and quantitation of human coronaviruses (HCoVs) OC43 and 229E. Absolute viral load measurement in clinical samples was achieved through the construction of in-house HCoV OC43 and 229E cRNA standards for the generation of a standard curve. The HCoV OC43 assay allows quantitation over a range from 20 to 2 × 10(8) RNA copies per reaction mixture (5 μl RNA extract). When this is extrapolated to clinical samples, this corresponds to a detection range of 10(3) to 10(10) viral genome equivalents per ml. By using the HCoV 229E qRT-PCR assay, viral RNA copies ranging from 200 to 2 × 10(9) per reaction mixture can be detected, which corresponds to 10(4) to 10(11) viral genome equivalents per ml sample. A total of 100 respiratory samples screened for the presence of HCoVs OC43 and 229E by using conventional RT-PCR were assessed in parallel by the qRT-PCR assays. By use of the real-time qRT-PCR techniques, the detection rate of HCoVs OC43 and 229E increased from 2.0% to 3.1% and from 0.3% to 2.5%, respectively. The real-time qRT-PCR assays described here allow the rapid, specific, and sensitive laboratory detection and quantitation of human coronaviruses OC43 and 229E.",,"['Vijgen, Leen', 'Keyaerts, Els', 'Moës, Elien', 'Maes, Piet', 'Duson, Griet', 'Van Ranst, Marc']",,,,
,PMC,TaqMan Real-Time Reverse Transcription-PCR and JDVp26 Antigen Capture Enzyme-Linked Immunosorbent Assay To Quantify Jembrana Disease Virus Load during the Acute Phase of In Vivo Infection,http://dx.doi.org/10.1128/JCM.43.11.5574-5580.2005,PMC1287780,,,"Jembrana disease virus (JDV) is an acutely pathogenic lentivirus that affects Bali cattle in Indonesia. The inability to propagate the virus in vitro has made it difficult to quantitate JDV and determine the kinetics of virus replication during the acute phase of the disease process. We report for the first time two techniques that enable quantification of the virus and the use of these techniques to quantify the virus load during the acute phase of the disease process. A one-step JDV pol TaqMan real-time reverse transcription-PCR (RT-PCR) assay was developed for the detection and quantification of JDV RNA in plasma. The limit of detection was 9.8 × 10(2) JDV viral RNA copies over 35 cycles, equivalent to 4.2 × 10(4) JDV genome copies/ml, and a peak virus load of 1.6 × 10(12) during the acute febrile period. An antigen capture enzyme-linked immunosorbent assay (ELISA) was also developed to quantify the levels of JDV capsid (JDVp26) over a linear range of 10 to 200 ng/ml. Viral RNA and JDVp26 levels were correlated in 48 plasma samples obtained from experimentally infected cattle. A significant positive correlation (R = 0.860 and r(2) = 0.740) was observed between the two techniques within the range of their detection limits. The relatively insensitive capture ELISA provides an economical and feasible method for monitoring of virus in the absence of more sensitive techniques.",,"['Stewart, Meredith', 'Desport, Moira', 'Hartaningsih, Nining', 'Wilcox, Graham']",,,,
,PMC,Use of Resequencing Oligonucleotide Microarrays for Identification of Streptococcus pyogenes and Associated Antibiotic Resistance Determinants,http://dx.doi.org/10.1128/JCM.43.11.5690-5695.2005,PMC1287778,,,"Group A streptococci (GAS) are responsible for a wide variety of human infections associated with considerable morbidity and mortality. Ever since the first systematic effort by Lancefield to group Streptococcus species by M protein variants, the detection and characterization of Streptococcus by different methods have been an evolving process. The ideal assay for GAS identification not only would provide quick and accurate diagnostic results but also would reveal antibiotic resistance patterns and genotype information, aiding not only in treatment but in epidemiologic assessment as well. The oligonucleotide microarray is a promising new technology which could potentially address this need. In this study, we evaluated the usefulness of oligonucleotide resequencing microarrays for identifying GAS and its associated antibiotic resistance markers. We demonstrated an assay platform that combines the use of resequencing DNA microarrays with either random nucleic acid amplification or multiplex PCR for GAS detection. When detecting Streptococcus pyogenes from coded clinical samples, this approach demonstrated an excellent concordance with a more established culture method. To this end, we showed the potential of resequencing microarrays for efficient and accurate detection of GAS and its associated antibiotic resistance markers with the benefit of sequencing information from microarray analysis.",,"['Davignon, Louis', 'Walter, Elizabeth A.', 'Mueller, Kate M.', 'Barrozo, Christopher P.', 'Stenger, David A.', 'Lin, Baochuan', None]",,,,
,PMC,Molecular Diagnosis of Severe Acute Respiratory Syndrome : The State of the Art,,PMC1867551,,,"Severe acute respiratory syndrome (SARS) first appeared in Guangdong Province, China, in November 2002. Although virus isolation and serology were useful early in the SARS outbreak for diagnosing new cases, these tests are not generally useful because virus culture requires a BSL-3 laboratory and seroconversion is often delayed until 2 to 3 weeks after infection. The first qualitative reverse transcriptase-polymerase chain reaction tests for SARS-coronavirus (CoV) were sensitive and capable of detecting 1 to 10 genome equivalents. These assays were quickly supplemented with quantitative real-time assays that helped elucidate the natural history of SARS, particularly the initial presence of low viral loads in the upper respiratory tract and high viral loads in the lower respiratory tract. The unique natural history of SARS-CoV infection dictates the testing of both respiratory and nonrespiratory specimens, the testing of multiple specimens from the same patient, and sending out positives to be confirmed by a reference laboratory. Commercially available reverse transcriptase-polymerase chain reaction tests for SARS have recently appeared; however, meaningful evaluations of these assays have not yet been performed and their true performance has not been determined. These and other issues related to diagnosis of SARS-CoV infection are discussed in this review.",,"['Mahony, James B.', 'Richardson, Susan']",,,,
,PMC,Stress-Activated Protein Kinases Are Involved in Coxsackievirus B3 Viral Progeny Release,http://dx.doi.org/10.1128/JVI.79.22.13875-13881.2005,PMC1280244,,,"Stress-activated protein kinases (SAPKs), consisting of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK), are activated upon various environmental stimuli, including viral infections. Cellular survival and death signaling events following coxsackievirus B3 (CVB3) infection have been studied in relationship to viral replication, but the role of SAPKs has not been scrutinized. In this study, we found that the phosphorylation of JNK1/2 and p38 MAPK was increased during active replication of CVB3 and that their phosphorylation was independent of CVB3-induced caspase activation or production of reactive oxygen species. The roles of these kinases in CVB3 infection were further evaluated using specific inhibitors: SP600125 for JNK1/2 and SB203580 for p38 MAPK. JNK1/2 inhibitors reduced CVB3-induced phosphorylation of activating transcription factor 2, and the p38 MAPK inhibitor reduced CVB3-induced phosphorylation of heat shock protein 27. Although inhibition of these kinases by specific inhibitors did not affect CVB3 viral protein synthesis, inhibition of p38 MAPK but not of JNK1/2 resulted in significant reduction of viral progeny release, suppression of CVB3-induced cell death, and blockage of CVB3-induced caspase-3 activation in infected cells. We conclude that SAPK pathways play critical roles in the life cycle of CVB3, particularly in viral progeny release.",,"['Si, Xiaoning', 'Luo, Honglin', 'Morgan, Andrew', 'Zhang, Jingchun', 'Wong, Jerry', 'Yuan, Ji', 'Esfandiarei, Mitra', 'Gao, Guang', 'Cheung, Caroline', 'McManus, Bruce M.']",,,,
,PMC,Murine Coronavirus with an Extended Host Range Uses Heparan Sulfate as an Entry Receptor,http://dx.doi.org/10.1128/JVI.79.22.14451-14456.2005,PMC1280238,,,"Only a relatively few mutations in its spike protein allow the murine coronavirus to switch from a murine-restricted tropism to an extended host range by being passaged in vitro. One such virus that we studied had acquired two putative heparan sulfate-binding sites while preserving another site in the furin-cleavage motif. The adaptation of the virus through the use of heparan sulfate as an attachment/entry receptor was demonstrated by increased heparin binding as well as by inhibition of infection through treatment of cells and the virus with heparinase and heparin, respectively.",,"['de Haan, Cornelis A. M.', 'Li, Zhen', 'te Lintelo, Eddie', 'Bosch, Berend Jan', 'Haijema, Bert Jan', 'Rottier, Peter J. M.']",,,,
,PMC,Acquisition of Macrophage Tropism during the Pathogenesis of Feline Infectious Peritonitis Is Determined by Mutations in the Feline Coronavirus Spike Protein,http://dx.doi.org/10.1128/JVI.79.22.14122-14130.2005,PMC1280227,,,"In feline coronavirus (FCoV) pathogenesis, the ability to infect macrophages is an essential virulence factor. Whereas the low-virulence feline enteric coronavirus (FECV) isolates primarily replicate in the epithelial cells of the enteric tract, highly virulent feline infectious peritonitis virus (FIPV) isolates have acquired the ability to replicate efficiently in macrophages, which allows rapid dissemination of the virulent virus throughout the body. FIPV 79-1146 and FECV 79-1683 are two genetically closely related representatives of the two pathotypes. Whereas FECV 79-1683 causes at the most a mild enteritis in young kittens, FIPV 79-1146 almost invariably induces a lethal peritonitis. The virulence phenotypes correlate with the abilities of these viruses to infect and replicate in macrophages, a feature of FIPV 79-1146 but not of FECV 79-1683. To identify the genetic determinants of the FIPV 79-1146 macrophage tropism, we exchanged regions of its genome with the corresponding parts of FECV 79-1683, after which the ability of the FIPV/FECV hybrid viruses to infect macrophages was tested. Thus, we established that the FIPV spike protein is the determinant for efficient macrophage infection. Interestingly, this property mapped to the C-terminal domain of the protein, implying that the difference in infection efficiency between the two viruses is not determined at the level of receptor usage, which we confirmed by showing that infection by both viruses was equally blocked by antibodies directed against the feline aminopeptidase N receptor. The implications of these findings are discussed.",,"['Rottier, Peter J. M.', 'Nakamura, Kazuya', 'Schellen, Pepijn', 'Volders, Haukeline', 'Haijema, Bert Jan']",,,,
,PMC,Modulation of the Immune Response to the Severe Acute Respiratory Syndrome Spike Glycoprotein by Gene-Based and Inactivated Virus Immunization,http://dx.doi.org/10.1128/JVI.79.22.13915-13923.2005,PMC1280202,,,"Although the initial isolates of the severe acute respiratory syndrome (SARS) coronavirus (CoV) are sensitive to neutralization by antibodies through their spike (S) glycoprotein, variants of S have since been identified that are resistant to such inhibition. Optimal vaccine strategies would therefore make use of additional determinants of immune recognition, either through cellular or expanded, cross-reactive humoral immunity. Here, the cellular and humoral immune responses elicited by different combinations of gene-based and inactivated viral particles with various adjuvants have been assessed. The T-cell response was altered by different prime-boost immunizations, with the optimal CD8 immunity induced by DNA priming and replication-defective adenoviral vector boosting. The humoral immune response was enhanced most effectively through the use of inactivated virus with adjuvants, either MF59 or alum, and was associated with stimulation of the CD4 but not the CD8 response. The use of inactivated SARS virus with MF59 enhanced the CD4 and antibody response even after gene-based vaccination. Because both cellular and humoral immune responses are generated by gene-based vaccination and inactivated viral boosting, this strategy may prove useful in the generation of SARS-CoV vaccines.",,"['Kong, Wing-pui', 'Xu, Ling', 'Stadler, Konrad', 'Ulmer, Jeffrey B.', 'Abrignani, Sergio', 'Rappuoli, Rino', 'Nabel, Gary J.']",,,,
,PMC,Assembly of Severe Acute Respiratory Syndrome Coronavirus RNA Packaging Signal into Virus-Like Particles Is Nucleocapsid Dependent,http://dx.doi.org/10.1128/JVI.79.22.13848-13855.2005,PMC1280188,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) was recently identified as the etiology of SARS. The virus particle consists of four structural proteins: spike (S), small envelope (E), membrane (M), and nucleocapsid (N). Recognition of a specific sequence, termed the packaging signal (PS), by a virus N protein is often the first step in the assembly of viral RNA, but the molecular mechanisms involved in the assembly of SARS-CoV RNA are not clear. In this study, Vero E6 cells were cotransfected with plasmids encoding the four structural proteins of SARS-CoV. This generated virus-like particles (VLPs) of SARS-CoV that can be partially purified on a discontinuous sucrose gradient from the culture medium. The VLPs bearing all four of the structural proteins have a density of about 1.132 g/cm(3). Western blot analysis of the culture medium from transfection experiments revealed that both E and M expressed alone could be released in sedimentable particles and that E and M proteins are likely to form VLPs when they are coexpressed. To examine the assembly of the viral genomic RNA, a plasmid representing the GFP-PS580 cDNA fragment encompassing the viral genomic RNA from nucleotides 19715 to 20294 inserted into the 3′ noncoding region of the green fluorescent protein (GFP) gene was constructed and applied to the cotransfection experiments with the four structural proteins. The SARS-CoV VLPs thus produced were designated VLP(GFP-PS580). Expression of GFP was detected in Vero E6 cells infected with the VLP(GFP-PS580), indicating that GFP-PS580 RNA can be assembled into the VLPs. Nevertheless, when Vero E6 cells were infected with VLPs produced in the absence of the viral N protein, no green fluorescence was visualized. These results indicate that N protein has an essential role in the packaging of SARS-CoV RNA. A filter binding assay and competition analysis further demonstrated that the N-terminal and C-terminal regions of the SARS-CoV N protein each contain a binding activity specific to the viral RNA. Deletions that presumably disrupt the structure of the N-terminal domain diminished its RNA-binding activity. The GFP-PS-containing SARS-CoV VLPs are powerful tools for investigating the tissue tropism and pathogenesis of SARS-CoV.",,"['Hsieh, Ping-Kun', 'Chang, Shin C.', 'Huang, Chu-Chun', 'Lee, Ting-Ting', 'Hsiao, Ching-Wen', 'Kou, Yi-Hen', 'Chen, I-Yin', 'Chang, Chung-Ke', 'Huang, Tai-Huang', 'Chang, Ming-Fu']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Fails To Activate Cytokine-Mediated Innate Immune Responses in Cultured Human Monocyte-Derived Dendritic Cells,http://dx.doi.org/10.1128/JVI.79.21.13800-13805.2005,PMC1262618,,,"Activation of host innate immune responses was studied in severe acute respiratory syndrome coronavirus (SCV)-infected human A549 lung epithelial cells, macrophages, and dendritic cells (DCs). In all cell types, SCV-specific subgenomic mRNAs were seen, whereas no expression of SCV proteins was found. No induction of cytokine genes (alpha interferon [IFN-α], IFN-β, interleukin-28A/B [IL-28A/B], IL-29, tumor necrosis factor alpha, CCL5, or CXCL10) or IFN-α/β-induced MxA gene was seen in SCV-infected A549 cells, macrophages, or DCs. SCV also failed to induce DC maturation (CD86 expression) or enhance major histocompatibility complex class II expression. Our data strongly suggest that SCV fails to activate host cell cytokine gene expression in human macrophages and DCs.",,"['Ziegler, Thedi', 'Matikainen, Sampsa', 'Rönkkö, Esa', 'Österlund, Pamela', 'Sillanpää, Maarit', 'Sirén, Jukka', 'Fagerlund, Riku', 'Immonen, Milla', 'Melén, Krister', 'Julkunen, Ilkka']",,,,
,PMC,The nsp2 Replicase Proteins of Murine Hepatitis Virus and Severe Acute Respiratory Syndrome Coronavirus Are Dispensable for Viral Replication,http://dx.doi.org/10.1128/JVI.79.21.13399-13411.2005,PMC1262610,,,"The positive-stranded RNA genome of the coronaviruses is translated from ORF1 to yield polyproteins that are proteolytically processed into intermediate and mature nonstructural proteins (nsps). Murine hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV) polyproteins incorporate 16 protein domains (nsps), with nsp1 and nsp2 being the most variable among the coronaviruses and having no experimentally confirmed or predicted functions in replication. To determine if nsp2 is essential for viral replication, MHV and SARS-CoV genome RNA was generated with deletions of the nsp2 coding sequence (MHVΔnsp2 and SARSΔnsp2, respectively). Infectious MHVΔnsp2 and SARSΔnsp2 viruses recovered from electroporated cells had 0.5 to 1 log(10) reductions in peak titers in single-cycle growth assays, as well as a reduction in viral RNA synthesis that was not specific for any positive-stranded RNA species. The Δnsp2 mutant viruses lacked expression of both nsp2 and an nsp2-nsp3 precursor, but cleaved the engineered chimeric nsp1-nsp3 cleavage site as efficiently as the native nsp1-nsp2 cleavage site. Replication complexes in MHVΔnsp2-infected cells lacked nsp2 but were morphologically indistinguishable from those of wild-type MHV by immunofluorescence. nsp2 expressed in cells by stable retroviral transduction was specifically recruited to viral replication complexes upon infection with MHVΔnsp2. These results demonstrate that while nsp2 of MHV and SARS-CoV is dispensable for viral replication in cell culture, deletion of the nsp2 coding sequence attenuates viral growth and RNA synthesis. These findings also provide a system for the study of determinants of nsp targeting and function.",,"['Graham, Rachel L.', 'Sims, Amy C.', 'Brockway, Sarah M.', 'Baric, Ralph S.', 'Denison, Mark R.']",,,,
,PMC,Contribution of Trafficking Signals in the Cytoplasmic Tail of the Infectious Bronchitis Virus Spike Protein to Virus Infection,http://dx.doi.org/10.1128/JVI.79.21.13209-13217.2005,PMC1262608,,,"Coronavirus spike (S) proteins are responsible for binding and fusion with target cells and thus play an essential role in virus infection. Recently, we identified a dilysine endoplasmic reticulum (ER) retrieval signal and a tyrosine-based endocytosis signal in the cytoplasmic tail of the S protein of infectious bronchitis virus (IBV). Here, an infectious cDNA clone of IBV was used to address the importance of the S protein trafficking signals to virus infection. We constructed infectious cDNA clones lacking the ER retrieval signal, the endocytosis signal, or both. The virus lacking the ER retrieval signal was viable. However, this virus had a growth defect at late times postinfection and produced larger plaques than IBV. Further analysis confirmed that the mutant S protein trafficked though the secretory pathway faster than wild-type S protein. A more dramatic phenotype was obtained when the endocytosis signal was mutated. Recombinant viruses lacking the endocytosis signal (in combination with a mutated dilysine signal or alone) could not be recovered, even though transient syncytia were formed in transfected cells. Our results suggest that the endocytosis signal of IBV S is essential for productive virus infection.",,"['Youn, Soonjeon', 'Collisson, Ellen W.', 'Machamer, Carolyn E.']",,,,
,PMC,Recombinant Newcastle Disease Virus Expressing a Foreign Viral Antigen Is Attenuated and Highly Immunogenic in Primates,http://dx.doi.org/10.1128/JVI.79.21.13275-13284.2005,PMC1262603,,,"Paramyxoviruses such as human parainfluenza viruses that bear inserts encoding protective antigens of heterologous viruses can induce an effective immunity against the heterologous viruses in experimental animals. However, vectors based on common human pathogens would be expected to be restricted in replication in the adult human population due to high seroprevalence, an effect that would reduce vector immunogenicity. To address this issue, we evaluated Newcastle disease virus (NDV), an avian paramyxovirus that is serotypically distinct from common human pathogens, as a vaccine vector. Two strains were evaluated: the attenuated vaccine strain LaSota (NDV-LS) that replicates mostly in the chicken respiratory tract and the Beaudette C (NDV-BC) strain of intermediate virulence that produces mild systemic infection in chickens. A recombinant version of each virus was modified by the insertion, between the P and M genes, of a gene cassette encoding the human parainfluenza virus type 3 (HPIV3) hemagglutinin-neuraminidase (HN) protein, a test antigen with considerable historic data. The recombinant viruses were administered to African green monkeys (NDV-BC and NDV-LS) and rhesus monkeys (NDV-BC only) by combined intranasal and intratracheal routes at a dose of 10(6.5) PFU per site, with a second equivalent dose administered 28 days later. Little or no virus shedding was detected in nose-throat swabs or tracheal lavages following immunization with either strain. In a separate experiment, direct examination of lung tissue confirmed a highly attenuated, restricted pattern of replication by parental NDV-BC. The serum antibody response to the foreign HN protein induced by the first immunization with either NDV vector was somewhat less than that observed following a wild-type HPIV3 infection; however, the titer following the second dose exceeded that observed with HPIV3 infection, even though HPIV3 replicates much more efficiently than NDV in these animals. NDV appears to be a promising vector for the development of vaccines for humans; one application would be in controlling localized outbreaks of emerging pathogens.",,"['Bukreyev, Alexander', 'Huang, Zhuhui', 'Yang, Lijuan', 'Elankumaran, Subbiah', 'St. Claire, Marisa', 'Murphy, Brian R.', 'Samal, Siba K.', 'Collins, Peter L.']",,,,
,PMC,A Major Determinant for Membrane Protein Interaction Localizes to the Carboxy-Terminal Domain of the Mouse Coronavirus Nucleocapsid Protein,http://dx.doi.org/10.1128/JVI.79.21.13285-13297.2005,PMC1262602,,,"The two major constituents of coronavirus virions are the membrane (M) and nucleocapsid (N) proteins. The M protein is anchored in the viral envelope by three transmembrane segments flanked by a short amino-terminal ectodomain and a large carboxy-terminal endodomain. The M endodomain interacts with the viral nucleocapsid, which consists of the positive-strand RNA genome helically encapsidated by N protein monomers. In previous work with the coronavirus mouse hepatitis virus (MHV), a highly defective M protein mutant, MΔ2, was constructed. This mutant contained a 2-amino-acid carboxy-terminal truncation of the M protein. Analysis of second-site revertants of MΔ2 revealed mutations in the carboxy-terminal region of the N protein that compensated for the defect in the M protein. To seek further genetic evidence corroborating this interaction, we generated a comprehensive set of clustered charged-to-alanine mutants in the carboxy-terminal domain 3 of N protein. One of these mutants, CCA4, had a highly defective phenotype similar to that of MΔ2. Transfer of the CCA4 mutation into a partially diploid MHV genome showed that CCA4 was a loss-of-function mutation rather than a dominant-negative mutation. Analysis of multiple second-site revertants of CCA4 revealed mutations in both the M protein and the N protein that could compensate for the original lesion in N. These data more precisely define the region of the N protein that interacts with the M protein. Further, we found that fusion of domain 3 of the N protein to the carboxy terminus of a heterologous protein caused it to be incorporated into MHV virions.",,"['Hurst, Kelley R.', 'Kuo, Lili', 'Koetzner, Cheri A.', 'Ye, Rong', 'Hsue, Bilan', 'Masters, Paul S.']",,,,
,PMC,A Norovirus Protease Structure Provides Insights into Active and Substrate Binding Site Integrity,http://dx.doi.org/10.1128/JVI.79.21.13685-13693.2005,PMC1262588,,,"Norovirus 3C-like proteases are crucial to proteolytic processing of norovirus polyproteins. We determined the crystal structure of the 3C-like protease from Chiba virus, a norovirus, at 2.8-Å resolution. An active site including Cys139 and His30 is present, as is a hydrogen bond network that stabilizes the active site conformation. In the oxyanion hole backbone, a structural difference was observed probably upon substrate binding. A peptide substrate/enzyme model shows that several interactions between the two components are critical for substrate binding and that the S1 and S2 sites appropriately accommodate the substrate P1 and P2 residues, respectively. Knowledge of the structure and a previous mutagenesis study allow us to correlate proteolysis and structure.",,"['Nakamura, Kentaro', 'Someya, Yuichi', 'Kumasaka, Takashi', 'Ueno, Go', 'Yamamoto, Masaki', 'Sato, Takao', 'Takeda, Naokazu', 'Miyamura, Tatsuo', 'Tanaka, Nobuo']",,,,
,PMC,Air Cleaning Technologies: An Evidence-Based Analysis,,PMC3382390,,,"OBJECTIVE: This health technology policy assessment will answer the following questions: When should in-room air cleaners be used? How effective are in-room air cleaners? Are in-room air cleaners that use combined HEPA and UVGI air cleaning technology more effective than those that use HEPA filtration alone? What is the Plasmacluster ion air purifier in the pandemic influenza preparation plan? The experience of severe acute respiratory syndrome (SARS) locally, nationally, and internationally underscored the importance of administrative, environmental, and personal protective infection control measures in health care facilities. In the aftermath of the SARS crisis, there was a need for a clearer understanding of Ontario’s capacity to manage suspected or confirmed cases of airborne infectious diseases. In so doing, the Walker Commission thought that more attention should be paid to the potential use of new technologies such as in-room air cleaning units. It recommended that the Medical Advisory Secretariat of the Ontario Ministry of Health and Long-Term Care evaluate the appropriate use and effectiveness of such new technologies. Accordingly, the Ontario Health Technology Advisory Committee asked the Medical Advisory Secretariat to review the literature on the effectiveness and utility of in-room air cleaners that use high-efficiency particle air (HEPA) filters and ultraviolet germicidal irradiation (UVGI) air cleaning technology. Additionally, the Ontario Health Technology Advisory Committee prioritized a request from the ministry’s Emergency Management Unit to investigate the possible role of the Plasmacluster ion air purifier manufactured by Sharp Electronics Corporation, in the pandemic influenza preparation plan. CLINICAL NEED: Airborne transmission of infectious diseases depends in part on the concentration of breathable infectious pathogens (germs) in room air. Infection control is achieved by a combination of administrative, engineering, and personal protection methods. Engineering methods that are usually carried out by the building’s heating, ventilation, and air conditioning (HVAC) system function to prevent the spread of airborne infectious pathogens by diluting (dilution ventilation) and removing (exhaust ventilation) contaminated air from a room, controlling the direction of airflow and the air flow patterns in a building. However, general wear and tear over time may compromise the HVAC system’s effectiveness to maintain adequate indoor air quality. Likewise, economic issues may curtail the completion of necessary renovations to increase its effectiveness. Therefore, when exposure to airborne infectious pathogens is a risk, the use of an in-room air cleaner to reduce the concentration of airborne pathogens and prevent the spread of airborne infectious diseases has been proposed as an alternative to renovating a HVAC system. Airborne transmission is the spread of infectious pathogens over large distances through the air. Infectious pathogens, which may include fungi, bacteria, and viruses, vary in size and can be dispersed into the air in drops of moisture after coughing or sneezing. Small drops of moisture carrying infectious pathogens are called droplet nuclei. Droplet nuclei are about 1 to 5μm in diameter. This small size in part allows them to remain suspended in the air for several hours and be carried by air currents over considerable distances. Large drops of moisture carrying infectious pathogens are called droplets. Droplets being larger than droplet nuclei, travel shorter distances (about 1 metre) before rapidly falling out of the air to the ground. Because droplet nuclei remain airborne for longer periods than do droplets, they are more amenable to engineering infection control methods than are droplets. Droplet nuclei are responsible for the airborne transmission of infectious diseases such as tuberculosis, chicken pox (varicella), measles (rubeola), and dessiminated herpes zoster, whereas close contact is required for the direct transmission of infectious diseases transmitted by droplets, such as influenza (the flu) and SARS. THE TECHNOLOGY: In-room air cleaners are supplied as portable or fixed devices. Fixed devices can be attached to either a wall or ceiling and are preferred over portable units because they have a greater degree of reliability (if installed properly) for achieving adequate room air mixing and airflow patterns, which are important for optimal effectiveness. Through a method of air recirculation, an in-room air cleaner can be used to increase room ventilation rates and if used to exhaust air out of the room it can create a negative-pressure room for airborne infection isolation (AII) when the building’s HVAC system cannot do so. A negative-pressure room is one where clean air flows into the room but contaminated air does not flow out of it. Contaminated room air is pulled into the in-room air cleaner and cleaned by passing through a series of filters, which remove the airborne infectious pathogens. The cleaned air is either recirculated into the room or exhausted outside the building. By filtering contaminated room air and then recirculating the cleaned air into the room, an in-room air cleaner can improve the room’s ventilation. By exhausting the filtered air to the outside the unit can create a negative-pressure room. There are many types of in-room air cleaners. They vary widely in the airflow rates through the unit, the type of air cleaning technology used, and the technical design. Crucial to maximizing the efficiency of any in-room air cleaner is its strategic placement and set-up within a room, which should be done in consultation with ventilation engineers, infection control experts, and/or industrial hygienists. A poorly positioned air cleaner may disrupt airflow patterns within the room and through the air cleaner, thereby compromising its air cleaning efficiency. The effectiveness of an in-room air cleaner to remove airborne pathogens from room air depends on several factors, including the airflow rate through the unit’s filter and the airflow patterns in the room. Tested under a variety of conditions, in-room air cleaners, including portable or ceiling mounted units with either a HEPA or a non-HEPA filter, portable units with UVGI lights only, or ceiling mounted units with combined HEPA filtration and UVGI lights, have been estimated to be between 30% and 90%, 99% and 12% and 80% effective, respectively. However, and although their effectiveness is variable, the United States Centers for Disease Control and Prevention has acknowledged in-room air cleaners as alternative technology for increasing room ventilation when this cannot be achieved by the building’s HVAC system with preference given to fixed recirculating systems over portable ones. Importantly, the use of an in-room air cleaner does not preclude either the need for health care workers and visitors to use personal protective equipment (N95 mask or equivalent) when entering AII rooms or health care facilities from meeting current regulatory requirements for airflow rates (ventilation rates) in buildings and airflow differentials for effective negative-pressure rooms. The Plasmacluster ion technology, developed in 2000, is an air purification technology. Its manufacturer, Sharp Electronics Corporation, says that it can disable airborne microorganisms through the generation of both positive and negative ions. (1) The functional unit is the hydroxyl, which is a molecule comprised of one oxygen molecule and one hydrogen atom. Plasmacluster ion air purifier uses a multilayer filter system composed of a prefilter, a carbon filter, an antibacterial filter, and a HEPA filter, combined with an ion generator to purify the air. The ion generator uses an alternating plasma discharge to split water molecules into positively and negatively charged ions. When these ions are emitted into the air, they are surrounded by water molecules and form cluster ions which are attracted to airborne particles. The cluster ion surrounds the airborne particle, and the positive and negative ions react to form hydroxyls. These hydroxyls steal the airborne particle’s hydrogen atom, which creates a hole in the particle’s outer protein membrane, thereby rendering it inactive. Because influenza is primarily acquired by large droplets and direct and indirect contact with an infectious person, any in-room air cleaner will have little benefit in controlling and preventing its spread. Therefore, there is no role for the Plasmacluster ion air purifier or any other in-room air cleaner in the control of the spread of influenza. Accordingly, for purposes of this review, the Medical Advisory Secretariat presents no further analysis of the Plasmacluster. REVIEW STRATEGY: The objective of the systematic review was to determine the effectiveness of in-room air cleaners with built in UVGI lights and HEPA filtration compared with those using HEPA filtration only. The Medical Advisory Secretariat searched the databases of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, INAHATA (International Network of Agencies for Health Technology Assessment), Biosis Previews, Bacteriology Abstracts, Web of Science, Dissertation Abstracts, and NIOSHTIC 2. A meta-analysis was conducted if adequate data was available from 2 or more studies and where statistical and clinical heterogeneity among studies was not an issue. Otherwise, a qualitative review was completed. The GRADE system was used to summarize the quality of the body of evidence comprised of 1 or more studies. SUMMARY OF FINDINGS: There were no existing health technology assessments on air cleaning technology located during the literature review. The literature search yielded 59 citations of which none were retained. One study was retrieved from a reference list of a guidance document from the United States Centers for Disease Control and Prevention, which evaluated an in-room air cleaner with combined UVGI lights and HEPA filtration under 2 conditions: UVGI lights on and UVGI lights off. Experiments were performed using different ventilation rates and using an aerosolized pathogen comprised of Mycobaterium parafortuitum, a surrogate for the bacterium that causes tuberculosis. Effectiveness was measured as equivalent air changes per hour (eACH). This single study formed the body of evidence for our systematic review research question. EXPERIMENTAL RESULTS: The eACH rate for the HEPA-UVGI in-room air cleaner was statistically significantly greater when the UV lights were on compared with when the UV lights were off. (P < .05). However, subsequent experiments could not attribute this to the UVGI. Consequently, the results are inconclusive and an estimate of effect (benefit) is uncertain. The study was reviewed by a scientific expert and rated moderate for quality. Further analysis determined that there was some uncertainty in the directness of the outcome measure (eACH); thus, the GRADE level for the quality of the evidence was low indicating that an estimate of effect is very uncertain. There is uncertainty in the benefits of using in-room air cleaners with combined UVGI lights and HEPA filtration over systems that use HEPA filtration alone. However, there are no known risks to using systems with combined UVGI and HEPA technology compared with those with HEPA alone. There is an increase in the burden of cost including capital costs (cost of the device), operating costs (electricity usage), and maintenance costs (cleaning and replacement of UVGI lights) to using an in-room air cleaner with combined UVGI and HEPA technology compared with those with HEPA alone. Given the uncertainty of the estimate of benefits, an in-room air cleaner with HEPA technology only may be an equally reasonable alternative to using one with combined UVGI and HEPA technology CONCLUSIONS: In-room air cleaners may be used to protect health care staff from air borne infectious pathogens such as tuberculosis, chicken pox, measles, and dessiminated herpes zoster. In addition, and although in-room air cleaners are not effective at protecting staff and preventing the spread of droplet-transmitted diseases such as influenza and SARS, they may be deployed in situations with a novel/emerging infectious agent whose epidemiology is not yet defined and where airborne transmission is suspected. It is preferable that in-room air cleaners be used with a fixed and permanent room placement when ventilation requirements must be improved and the HVAC system cannot be used. However, for acute (temporary) situations where a novel/emerging infectious agent presents whose epidemiology is not yet defined and where airborne transmission is suspected it may be prudent to use the in room air cleaner as a portable device until mode of transmission is confirmed. To maximize effectiveness, consultation with an environmental engineer and infection control expert should be undertaken before using an in-room air cleaner and protocols for maintenance and monitoring of these devices should be in place. If properly installed and maintained, in room air cleaners with HEPA or combined HEPA and UVGI air cleaning technology are effective in removing airborne pathogens. However, there is only weak evidence available at this time regarding the benefit of using an in-room air cleaner with combined HEPA and UVGI air cleaner technology instead of those with HEPA filter technology only.",,,,,,
,PMC,ACUTE RESPIRATORY DISTRESS SYNDROME IN A CHILD WITH HUMAN PARVOVIRUS B19 INFECTION,,PMC2896321,,,"A 6-year-old girl developed shock and multiple organ dysfunction including acute respiratory distress syndrome in association with parvovirus B19 infection. The diagnosis was based on positive antibodies and the detection of parvovirus 19 DNA in serum, bronchial secretions and skin biopsy. It seems likely, but it was not proved, that the parvovirus infection caused acute respiratory distress syndrome.",,"['Ferraz, Cláudia', 'Cunha, Francisco', 'Mota, Teresa C.', 'Carvalho, José M.', 'Simões, Joana S.', 'Aparicio, José M.']",,,,
,PMC,"Bird flu poses no immediate threat to Europe, leading virologist claims",,PMC1273475,,,,,"Sheldon, Tony",,,,
,PMC,Combating the free movement of micro-organisms,,PMC1273446,,,"Zsuzsanna Jakab, the head of the new European centre for disease control, tells Rory Watson that the centre should enable Europe to mount a more coordinated response to the threat from avian flu than it managed to the SARS epidemic",,"Watson, Rory",,,,
,PMC,Hydrolysis of Angiotensin Peptides by Human Angiotensin I–Converting Enzyme and the Resensitization of B(2) Kinin Receptors,http://dx.doi.org/10.1161/01.HYP.0000188905.20884.63,PMC1564276,,,"We measured the cleavage of angiotensin I (Ang I) metabolites by angiotensin I– converting enzyme (ACE) in cultured cells and examined how they augment actions of bradykinin B(2) receptor agonists. Monolayers of Chinese hamster ovary cells transfected to stably express human ACE and bradykinin B(2) receptors coupled to green fluorescent protein (B(2)GFP) or to express only coupled B(2)GFP receptors. We used 2 ACE-resistant bradykinin analogues to activate the B(2) receptors. We used high-performance liquid chromatography to analyze the peptides cleaved by ACE on cell monolayers and found that Ang 1-9 was hydrolyzed 18× slower than Ang I and ≈30% slower than Ang 1-7. Ang 1-7 was cleaved to Ang 1-5. Although μmol/L concentrations of slowly cleaved substrates Ang 1-7 and Ang 1-9 inhibit ACE, they resensitize the desensitized B(2)GFP receptors in nmol/L concentration, independent of ACE inhibition. This is reflected by release of arachidonic acid through a mechanism involving cross-talk between ACE and B(2) receptors. When ACE was not expressed, the Ang 1-9, Ang 1-7 peptides were inactive. Inhibitors of protein kinase C-α, phosphatases and Tyr-kinase blocked this resensitization activity, but not basal B(2) activation by bradykinin. Ang 1-9 and Ang 1-7 enhance bradykinin activity, probably by acting as endogenous allosteric modifiers of the ACE and B(2) receptor complex. Consequently, when ACE inhibitors block conversion of Ang I, other enzymes can still release Ang I metabolites to enhance the efficacy of ACE inhibitors.",,"['Chen, Zhenlong', 'Tan, Fulong', 'Erdös, Ervin G.', 'Deddish, Peter A.']",,,,
,PMC,"East Asia is most at risk of human flu epidemic, experts say",,PMC1261177,,,,,"Day, Michael",,,,
,PMC,"Receptor-binding domain of SARS-Cov spike protein: Soluble expression in E.coli, purification and functional characterization",http://dx.doi.org/10.3748/wjg.v11.i39.6159,PMC4436633,,,"AIM: To find a soluble and functional recombinant receptor-binding domain of severe acute respiratory syndrome-associated coronavirus (SARS-Cov), and to analyze its receptor binding ability. METHODS: Three fusion tags (glutathione S-transferase, GST; thioredoxin, Trx; maltose-binding protein, MBP), which preferably contributes to increasing solubility and to facilitating the proper folding of heteroprotein, were used to acquire the soluble and functional expression of RBD protein in Escherichia coli (BL21(DE3) and Rosetta-gamiB(DE3) strains). The receptor binding ability of the purified soluble RBD protein was then detected by ELISA and flow cytometry assay. RESULTS: RBD of SARS-Cov spike protein was expressed as inclusion body when fused as TrxA tag form in both BL21 (DE3) and Rosetta-gamiB (DE3) under many different cultures and induction conditions. And there was no visible expression band on SDS-PAGE when RBD was expressed as MBP tagged form. Only GST tagged RBD was soluble expressed in BL21(DE3), and the protein was purified by ÄKTA Prime Chromatography system. The ELISA data showed that GST.RBD antigen had positive reaction with anti-RBD mouse monoclonal antibody 1A5. Further flow cytometry assay demonstrated the high efficiency of RBD's binding ability to ACE2 (angiotensin-converting enzyme 2) positive Vero E6 cell. And ACE2 was proved as a cellular receptor that meditated an initial-affinity interaction with SARS-Cov spike protein. The geometrical mean of GST and GST.RBD binding to Vero E6 cells were 77.08 and 352.73 respectively. CONCLUSION: In this paper, we get sufficient soluble N terminal GST tagged RBD protein expressed in E.coli BL21(DE3); data from ELISA and flow cytometry assay demo-nstrate that the recombinant protein is functional and binding to ACE2 positive Vero E6 cell efficiently. And the recombinant RBD derived from E.coli can be used to developing subunit vaccine to block S protein binding with receptor and to neutralizing SARS-Cov infection.",,"['Chen, Jing', 'Miao, Lin', 'Li, Jia-Ming', 'Li, Yan-Ying', 'Zhu, Qing-Yu', 'Zhou, Chang-Lin', 'Fang, Hong-Qing', 'Chen, Hui-Peng']",,,,
,PMC,Structure of the SARS coronavirus main proteinase as an active C(2) crystallographic dimer,http://dx.doi.org/10.1107/S1744309105033257,PMC1978130,,,"The 34 kDa main proteinase (M(pro)) from the severe acute respiratory syndrome coronavirus (SARS-CoV) plays an important role in the virus life cycle through the specific processing of viral polyproteins. As such, SARS-CoV M(pro) is a key target for the identification of specific inhibitors directed against the SARS virus. With a view to facilitating the development of such compounds, crystals were obtained of the enzyme at pH 6.5 in the orthorhombic space group P2(1)2(1)2 that diffract to a resolution of 1.9 Å. These crystals contain one monomer per asymmetric unit and the biologically active dimer is generated via the crystallographic twofold axis. The conformation of the catalytic site indicates that the enzyme is active in the crystalline form and thus suitable for structure-based inhibition studies.",,"['Xu, Ting', 'Ooi, Amy', 'Lee, Hooi Chen', 'Wilmouth, Rupert', 'Liu, Ding Xiang', 'Lescar, Julien']",,,,
,PMC,"Indole alkaloid marine natural products: An established source of cancer drug leads with considerable promise for the control of parasitic, neurological and other diseases",http://dx.doi.org/10.1016/j.lfs.2005.09.007,PMC4918921,,,"The marine environment produces natural products from a variety of structural classes exhibiting activity against numerous disease targets. Historically marine natural products have largely been explored as anticancer agents. The indole alkaloids are a class of marine natural products that show unique promise in the development of new drug leads. This report reviews the literature on indole alkaloids of marine origin and also highlights our own research. Specific biological activities of indole alkaloids presented here include: cytotoxicity, antiviral, antiparasitic, anti-inflammatory, serotonin antagonism, Ca-releasing, calmodulin antagonism, and other pharmacological activities.",,"['Gul, Waseem', 'Hamann, Mark T.']",,,,
,PMC,Human Coronavirus NL63 Is Not Detected in the Respiratory Tracts of Children with Acute Kawasaki Disease,http://dx.doi.org/10.1086/497170,PMC2888540,,,"Kawasaki disease (KD) is a self-limited, systemic vasculitis of children for which an infectious trigger is suspected. Recently, an association between KD and human coronavirus (HCoV)–New Haven (NH) was reported, on the basis of polymerase chain reaction (PCR) with primers that also amplified HCoV-NL63. We investigated the possible association between these HCoVs in the respiratory tract and KD by reverse-transcriptase (RT) PCR and viral culture in a geographically and ethnically diverse population. Only 1 (2%) of 48 patients with acute KD was positive by RT-PCR for HCoV-NL63/NH in a nasopharyngeal swab. These data do not support an association between these HCoVs and KD.",,"['Shimizu, Chisato', 'Shike, Hiroko', 'Baker, Susan C.', 'Garcia, Francesca', 'van der Hoek, Lia', 'Kuijpers, Taco W.', 'Reed, Sharon L.', 'Rowley, Anne H.', 'Shulman, Stanford T.', 'Talbot, Helen K. B.', 'Williams, John V.', 'Burns, Jane C.']",,,,
,PMC,Aetiological role of viral and bacterial infections in acute adult lower respiratory tract infection (LRTI) in primary care,http://dx.doi.org/10.1136/thx.2004.027441,PMC2080713,,,"BACKGROUND: Lower respiratory tract infections (LRTI) are a common reason for consulting general practitioners (GPs). In most cases the aetiology is unknown, yet most result in an antibiotic prescription. The aetiology of LRTI was investigated in a prospective controlled study. METHODS: Eighty adults presenting to GPs with acute LRTI were recruited together with 49 controls over 12 months. Throat swabs, nasal aspirates (patients and controls), and sputum (patients) were obtained and polymerase chain reaction (PCR) and reverse transcriptase polymerase chain reaction (RT‐PCR) assays were used to detect Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, influenza viruses (AH1, AH3 and B), parainfluenza viruses 1–3, coronaviruses, respiratory syncytial virus, adenoviruses, rhinoviruses, and enteroviruses. Standard sputum bacteriology was also performed. Outcome was recorded at a follow up visit. RESULTS: Potential pathogens were identified in 55 patients with LRTI (69%) and seven controls (14%; p<0.0001). The identification rate was 63% (viruses) and 26% (bacteria) for patients and 12% (p<0.0001) and 6% (p = 0.013), respectively, for controls. The most common organisms identified in the patients were rhinoviruses (33%), influenza viruses (24%), and Streptococcus pneumoniae (19%) compared with 2% (p<0.001), 6% (p = 0.013), and 4% (p = 0.034), respectively, in controls. Multiple pathogens were identified in 18 of the 80 LRTI patients (22.5%) and in two of the 49 controls (4%; p = 0.011). Atypical organisms were rarely identified. Cases with bacterial aetiology were clinically indistinguishable from those with viral aetiology. CONCLUSION: Patients presenting to GPs with acute adult LRTI predominantly have a viral illness which is most commonly caused by rhinoviruses and influenza viruses.",,"['Creer, D D', 'Dilworth, J P', 'Gillespie, S H', 'Johnston, A R', 'Johnston, S L', 'Ling, C', 'Patel, S', 'Sanderson, G', 'Wallace, P G', 'McHugh, T D']",,,,
,PMC,Dynamic effects of antibody-dependent enhancement on the fitness of viruses,http://dx.doi.org/10.1073/pnas.0507320102,PMC1257724,,,"Antibody-dependent enhancement (ADE), a phenomenon in which viral replication is increased rather than decreased by immune sera, has been observed in vitro for a large number of viruses of public health importance, including flaviviruses, coronaviruses, and retroviruses. The most striking in vivo example of ADE in humans is dengue hemorrhagic fever, a disease in which ADE is thought to increase the severity of clinical manifestations of dengue virus infection by increasing virus replication. We examine the epidemiological impact of ADE on the prevalence and persistence of viral serotypes. Using a dynamical system model of n cocirculating dengue serotypes, we find that ADE may provide a competitive advantage to those serotypes that undergo enhancement compared with those that do not, and that this advantage increases with increasing numbers of cocirculating serotypes. Paradoxically, there are limits to the selective advantage provided by increasing levels of ADE, because greater levels of enhancement induce large amplitude oscillations in incidence of all dengue virus infections, threatening the persistence of both the enhanced and nonenhanced serotypes. Although the models presented here are specifically designed for dengue, our results are applicable to any epidemiological system in which partial immunity increases pathogen replication rates. Our results suggest that enhancement is most advantageous in settings where multiple serotypes circulate and where a large host population is available to support pathogen persistence during the deep troughs of ADE-induced large amplitude oscillations of virus replication.",,"['Cummings, Derek A. T.', 'Schwartz, Ira B.', 'Billings, Lora', 'Shaw, Leah B.', 'Burke, Donald S.']",,,,
,PMC,,,PMC1246105,,,,,,,,,
,PMC,Electrochemical Molecular Analysis Without Nucleic Acid Amplification,http://dx.doi.org/10.1016/j.ymeth.2005.05.008,PMC1564062,,,"Electrochemical biosensors have revolutionized glucose monitoring but have not yet fulfilled their promise of a low cost, direct detection replacement for genetic amplification tests such as PCR [K. Kerman, M. Kobayashi, E. Tamiya, Recent trends in electro-chemical DNA biosensor technology, Meas. Sci. Technol. 15 (2004) R1-R11; A. Chaubey, B.D. Malhotra, Mediated biosensors. Biosens. Bioelectron. 17 (6-7) (2002) 441-456]. It has been anticipated that the integration of nanoscale chemical structures such as self-assembled monolayers with electrochemical biosensors would increase sensitivity by decreasing inherent system noise. We have designed a novel biosensing approach incorporating such integration and achieved rapid, ultra-low concentration sensitivities without target amplification. Raw samples are mixed with lysis buffer to allow hybridization of nucleic acid targets with anchor and signal probes before immobilizing a signaling enzyme proximate to the biosensor surface. A bias potential is subsequently applied and the secondary byproduct of a cyclic peroxidase reaction measured. Further studies have demonstrated the application of our approach in protein, clinical chemistry, and ionic assays.",,"['Gau, Vincent', 'Ma, Shu-Ching', 'Wang, Hua', 'Tsukuda, Joni', 'Kibler, John', 'Haake, David A.']",,,,
,PMC,A human monoclonal antibody neutralizes diverse HIV-1 isolates by binding a critical gp41 epitope,http://dx.doi.org/10.1073/pnas.0506927102,PMC1253587,,,"HIV-1 entry into cells is mediated by the envelope glycoprotein receptor-binding (gp120) and membrane fusion-promoting (gp41) subunits. The gp41 heptad repeat 1 (HR1) domain is the molecular target of the fusion-inhibitor drug enfuvirtide (T20). The HR1 sequence is highly conserved and therefore considered an attractive target for vaccine development, but it is unknown whether antibodies can access HR1. Herein, we use gp41-based peptides to select a human antibody, 5H/I1-BMV-D5 (D5), that binds to HR1 and inhibits the assembly of fusion intermediates in vitro. D5 inhibits the replication of diverse HIV-1 clinical isolates and therefore represents a previously unknown example of a crossneutralizing IgG selected by binding to designed antigens. NMR studies and functional analyses map the D5-binding site to a previously identified hydrophobic pocket situated in the HR1 groove. This hydrophobic pocket was proposed as a drug target and subsequently identified as a common binding site for peptide and peptidomimetic fusion inhibitors. The finding that the D5 fusion-inhibitory antibody shares the same binding site suggests that the hydrophobic pocket is a “hot spot” for fusion inhibition and an ideal target on which to focus a vaccine-elicited antibody response. Our data provide a structural framework for the design of new immunogens and therapeutic antibodies with crossneutralizing potential.",,"['Miller, Michael D.', 'Geleziunas, Romas', 'Bianchi, Elisabetta', 'Lennard, Simon', 'Hrin, Renee', 'Zhang, Hangchun', 'Lu, Meiqing', 'An, Zhiqiang', 'Ingallinella, Paolo', 'Finotto, Marco', 'Mattu, Marco', 'Finnefrock, Adam C.', 'Bramhill, David', 'Cook, James', 'Eckert, Debra M.', 'Hampton, Richard', 'Patel, Mayuri', 'Jarantow, Stephen', 'Joyce, Joseph', 'Ciliberto, Gennaro', 'Cortese, Riccardo', 'Lu, Ping', 'Strohl, William', 'Schleif, William', 'McElhaugh, Michael', 'Lane, Steven', 'Lloyd, Christopher', 'Lowe, David', 'Osbourn, Jane', 'Vaughan, Tristan', 'Emini, Emilio', 'Barbato, Gaetano', 'Kim, Peter S.', 'Hazuda, Daria J.', 'Shiver, John W.', 'Pessi, Antonello']",,,,
,PMC,A transcriptional signaling pathway in the IFN system mediated by 2′-5′-oligoadenylate activation of RNase L,http://dx.doi.org/10.1073/pnas.0507551102,PMC1239948,,,"Virus replication in higher vertebrates is restrained by IFNs that cause cells to transcribe genes encoding antiviral proteins, such as 2′-5′ oligoadenylate synthetases. 2′-5′ oligoadenylate synthetase is stimulated by dsRNA to produce 5′-phosphorylated, 2′-5′-linked oligoadenylates (2-5A), whose function is to activate RNase L. Although RNase L is required for a complete IFN antiviral response and mutations in the RNase L gene (RNASEL or HPC1) increase prostate cancer rates, it is unknown how 2-5A affects these biological endpoints through its receptor, RNase L. Presently, we show that 2-5A activation of RNase L produces a remarkable stimulation of transcription (≥20-fold) for genes that suppress virus replication and prostate cancer. Unexpectedly, exposure of DU145 prostate cancer cells to physiologic levels of 2-5A (0.1 μM) induced approximately twice as many RNA species as it down-regulated. Among the 2-5A-induced genes are several IFN-stimulated genes, including IFN-inducible transcript 1/P56, IFN-inducible transcript 2/P54, IL-8, and IFN-stimulated gene 15. 2-5A also potently elevated RNA for macrophage inhibitory cytokine-1/nonsteroidal antiinflammatory drug-activated gene-1, a TGF-β superfamily member implicated as an apoptotic suppressor of prostate cancer. Transcriptional signaling to the macrophage inhibitory cytokine-1/nonsteroidal antiinflammatory drug-activated gene-1 promoter by 2-5A was deficient in HeLa cells expressing a nuclease-dead mutant of RNase L and was dependent on the mitogen-activated protein kinases c-Jun N-terminal kinase and extracellular signal-regulated kinase, both of which were activated in response to 2-5A treatments. Because 2-5A and RNase L participate in defenses against viral infections and prostate cancer, our findings have implications for basic cellular mechanisms that control major pathogenic processes.",,"['Malathi, Krishnamurthy', 'Paranjape, Jayashree M.', 'Bulanova, Elena', 'Shim, Minsub', 'Guenther-Johnson, Jeanna M.', 'Faber, Pieter W.', 'Eling, Thomas E.', 'Williams, Bryan R. G.', 'Silverman, Robert H.']",,,,
,PMC,"Chemokine up-regulation in SARS-coronavirus–infected, monocyte-derived human dendritic cells",http://dx.doi.org/10.1182/blood-2004-10-4166,PMC1895271,,,"Lymphopenia and increasing viral load in the first 10 days of severe acute respiratory syndrome (SARS) suggested immune evasion by SARS-coronavirus (CoV). In this study, we focused on dendritic cells (DCs) which play important roles in linking the innate and adaptive immunity. SARS-CoV was shown to infect both immature and mature human monocyte-derived DCs by electron microscopy and immunofluorescence. The detection of negative strands of SARS-CoV RNA in DCs suggested viral replication. However, no increase in viral RNA was observed. Using cytopathic assays, no increase in virus titer was detected in infected DCs and cell-culture supernatant, confirming that virus replication was incomplete. No induction of apoptosis or maturation was detected in SARS-CoV–infected DCs. The SARS-CoV–infected DCs showed low expression of antiviral cytokines (interferon α [IFN-α], IFN-β, IFN-γ, and interleukin 12p40 [IL-12p40]), moderate up-regulation of proinflammatory cytokines (tumor necrosis factor α [TNF-α] and IL-6) but significant up-regulation of inflammatory chemokines (macrophage inflammatory protein 1α [MIP-1α], regulated on activation normal T cell expressed and secreted [RANTES]), interferon-inducible protein of 10 kDa [IP-10], and monocyte chemoattractant protein 1 [MCP-1]). The lack of antiviral cytokine response against a background of intense chemokine up-regulation could represent a mechanism of immune evasion by SARS-CoV.",,"['Law, Helen K. W.', 'Cheung, Chung Yan', 'Ng, Hoi Yee', 'Sia, Sin Fun', 'Chan, Yuk On', 'Luk, Winsie', 'Nicholls, John M.', 'Peiris, J. S. Malik', 'Lau, Yu Lung']",,,,
,PMC,Feline Coronavirus Serotypes 1 and 2: Seroprevalence and Association with Disease in Switzerland,http://dx.doi.org/10.1128/CDLI.12.10.1209-1215.2005,PMC1247821,,,"To determine the prevalence of antibodies to feline coronavirus (FCoV) serotypes 1 and 2 in Switzerland and their association with different disease manifestations, a serological study based on immunofluorescence tests was conducted with Swiss field cats using transmissible gastroenteritis virus (TGEV), FCoV type 1 and FCoV type 2 as antigens. A total of 639 serum samples collected in the context of different studies from naturally infected cats were tested. The current study revealed that, with an apparent prevalence of 83%, FCoV serotype 1 is the most prevalent serotype in Switzerland. FCoV type 1 viruses induced higher antibody titers than FCoV type 2, and were more frequently associated with clinical signs and/or feline infectious peritonitis. The antibody development in seven cats experimentally infected with FCoV type 1 revealed that, with progressing duration of infection, antibodies to FCoV type 1 significantly increased over those to FCoV type 2. There was a significant relationship between antibody titers against TGEV, FCoV 1, and FCoV 2 and TGEV antigen detected the highest proportion of seropositive cats. We conclude that a vaccine against FCoV should be based on FCoV type 1-related antigens and that for serodiagnosis of FCoV infection TGEV should be used to attain the highest diagnostic efficiency. When serology is used in addition to clinical signs, hematology, and clinical chemistry results as an aid to diagnose clinical FIP, TGEV shows a diagnostic efficiency equal to that of a FCoV antigen.",,"['Kummrow, Maya', 'Meli, Marina L.', 'Haessig, Michael', 'Goenczi, Enikoe', 'Poland, Amy', 'Pedersen, Niels C.', 'Hofmann-Lehmann, Regina', 'Lutz, Hans']",,,,
,PMC,Excellence in Research and Education at the John A. Burns School of Medicine: A Tribute to Edwin Cadman’s Vision,,PMC1524877,,,,,"['Shomaker, T.S.', 'Easa, David', 'Harrigan, Rosanne', 'Berry, Marla', 'Gubler, Duane', 'Andrade, Naleen', 'Mau, Marjorie', 'Palafox, Neal', 'Blanchette, Patricia L', 'Rayner, Martin', 'Kasuya, Richard', 'Withy, Kelly', 'Davis, James']",,,,
,PMC,Control of Viral Infectivity by Tripartite Motif Proteins,http://dx.doi.org/10.1089/hum.2005.16.1125,PMC3556579,,,"It is of great interest to understand the molecular details of the pathways that constitute species barriers to viral infection. The tripartite motif protein TRIM5α has emerged as an important mediator of species-specific retroviral replication and innate immunity. This review considers the role of TRIM5α as an antiviral protein in mammals. The methods used to identify species-specific restriction to retroviral infection, and the identification of TRIM5α itself, are outlined. TRIM5α mediates an early postentry block to sensitive retroviral infection, usually before viral DNA synthesis. Results from mutational analysis of TRIM5α and their contribution to a mechanistic model for TRIM5α antiviral activity are discussed. The antiviral role of other TRIM proteins is considered, as is the role of TRIM5α cytoplasmic bodies.",,"TOWERS, GREG J.",,,,
,PMC,Comments on “The Impact of SARS on Medical House Staff …”,http://dx.doi.org/10.1111/j.1525-1497.2005.051391_3.x,PMC1490239,,,,,"['Lam, Carolyn SP', 'Yeo, Crystal-Jing', 'Cheong, Pak-Yean', 'Ho, Khek-Yu']",,,,
,PMC,Scalable Transcriptional Analysis Routine—Multiplexed Quantitative Real-Time Polymerase Chain Reaction Platform for Gene Expression Analysis and Molecular Diagnostics,,PMC1888488,,,"We report the development of a new technology for simultaneous quantitative detection of multiple targets in a single sample. Scalable transcriptional analysis routine (STAR) represents a novel integration of reverse transcriptase-polymerase chain reaction and capillary electrophoresis that allows detection of dozens of gene transcripts in a multiplexed format using amplicon size as an identifier for each target. STAR demonstrated similar or better sensitivity and precision compared to two commonly used methods, SYBR Green-based and TaqMan probe-based real-time reverse transcriptase-polymerase chain reaction. STAR can be used as a flexible platform for building a variety of applications to monitor gene expression, from single gene assays to assays analyzing the expression level of multiple genes. Using severe acute respiratory syndrome (SARS) corona virus as a model system, STAR technology detected single copies of the viral genome in a two-gene multiplex. Blinded studies using RNA extracted from various tissues of a SARS-infected individual showed that STAR correctly identified all samples containing SARS virus and yielded negative results for non-SARS control samples. Using alternate priming strategies, STAR technology can be adapted to transcriptional profiling studies without requiring a priori sequence information. Thus, STAR technology offers a flexible platform for development of highly multiplexed assays in gene expression analysis and molecular diagnostics.",,"['Garcia, Elizabeth P.', 'Dowding, Lori A.', 'Stanton, Lawrence W.', 'Slepnev, Vladimir I.']",,,,
,PMC,Structural Genomics of the Severe Acute Respiratory Syndrome Coronavirus: Nuclear Magnetic Resonance Structure of the Protein nsP7,http://dx.doi.org/10.1128/JVI.79.20.12905-12913.2005,PMC1235862,,,"Here, we report the three-dimensional structure of severe acute respiratory syndrome coronavirus (SARS-CoV) nsP7, a component of the SARS-CoV replicase polyprotein. The coronavirus replicase carries out regulatory tasks involved in the maintenance, transcription, and replication of the coronavirus genome. nsP7 was found to assume a compact architecture in solution, which is comprised primarily of helical secondary structures. Three helices (α2 to α4) form a flat up-down-up antiparallel α-helix sheet. The N-terminal segment of residues 1 to 22, containing two turns of α-helix and one turn of 3(10)-helix, is packed across the surface of α2 and α3 in the helix sheet, with the α-helical region oriented at a 60° angle relative to α2 and α3. The surface charge distribution is pronouncedly asymmetrical, with the flat surface of the helical sheet showing a large negatively charged region adjacent to a large hydrophobic patch and the opposite side containing a positively charged groove that extends along the helix α1. Each of these three areas is thus implicated as a potential site for protein-protein interactions.",,"['Peti, Wolfgang', 'Johnson, Margaret A.', 'Herrmann, Torsten', 'Neuman, Benjamin W.', 'Buchmeier, Michael J.', 'Nelson, Mike', 'Joseph, Jeremiah', 'Page, Rebecca', 'Stevens, Raymond C.', 'Kuhn, Peter', 'Wüthrich, Kurt']",,,,
,PMC,"ADP-Ribose-1""-Monophosphatase: a Conserved Coronavirus Enzyme That Is Dispensable for Viral Replication in Tissue Culture",http://dx.doi.org/10.1128/JVI.79.20.12721-12731.2005,PMC1235854,,,"Replication of the ∼30-kb plus-strand RNA genome of coronaviruses and synthesis of an extensive set of subgenome-length RNAs are mediated by the replicase-transcriptase, a membrane-bound protein complex containing several cellular proteins and up to 16 viral nonstructural proteins (nsps) with multiple enzymatic activities, including protease, polymerase, helicase, methyltransferase, and RNase activities. To get further insight into the replicase gene-encoded functions, we characterized the coronavirus X domain, which is part of nsp3 and has been predicted to be an ADP-ribose-1""-monophosphate (Appr-1""-p) processing enzyme. Bacterially expressed forms of human coronavirus 229E (HCoV-229E) and severe acute respiratory syndrome-coronavirus X domains were shown to dephosphorylate Appr-1""-p, a side product of cellular tRNA splicing, to ADP-ribose in a highly specific manner. The enzyme had no detectable activity on several other nucleoside phosphates. Guided by the crystal structure of AF1521, an X domain homolog from Archaeoglobus fulgidus, potential active-site residues of the HCoV-229E X domain were targeted by site-directed mutagenesis. The data suggest that the HCoV-229E replicase polyprotein residues, Asn 1302, Asn 1305, His 1310, Gly 1312, and Gly 1313, are part of the enzyme's active site. Characterization of an Appr-1""-pase-deficient HCoV-229E mutant revealed no significant effects on viral RNA synthesis and virus titer, and no reversion to the wild-type sequence was observed when the mutant virus was passaged in cell culture. The apparent dispensability of the conserved X domain activity in vitro indicates that coronavirus replicase polyproteins have evolved to include nonessential functions. The biological significance of the novel enzymatic activity in vivo remains to be investigated.",,"['Putics, Ákos', 'Filipowicz, Witold', 'Hall, Jonathan', 'Gorbalenya, Alexander E.', 'Ziebuhr, John']",,,,
,PMC,Coronaviruses as Vectors: Stability of Foreign Gene Expression,http://dx.doi.org/10.1128/JVI.79.20.12742-12751.2005,PMC1235832,,,"Coronaviruses are enveloped, positive-stranded RNA viruses considered to be promising vectors for vaccine development, as (i) genes can be deleted, resulting in attenuated viruses; (ii) their tropism can be modified by manipulation of their spike protein; and (iii) heterologous genes can be expressed by simply inserting them with appropriate coronaviral transcription signals into the genome. For any live vector, genetic stability is an essential requirement. However, little is known about the genetic stability of recombinant coronaviruses expressing foreign genes. In this study, the Renilla and the firefly luciferase genes were systematically analyzed for their stability after insertion at various genomic positions in the group 1 coronavirus feline infectious peritonitis virus and in the group 2 coronavirus mouse hepatitis virus. It appeared that the two genes exhibit intrinsic differences, the Renilla gene consistently being maintained more stably than the firefly gene. This difference was not caused by genome size restrictions, by different effects of the encoded proteins, or by different consequences of the synthesis of the additional subgenomic mRNAs. The loss of expression of the firefly luciferase was found to result from various, often large deletions of the gene, probably due to RNA recombination. The extent of this process appeared to depend strongly on the coronaviral genomic background, the luciferase gene being much more stable in the feline than in the mouse coronavirus genome. It also depended significantly on the particular genomic location at which the gene was inserted. The data indicate that foreign sequences are more stably maintained when replacing nonessential coronaviral genes.",,"['de Haan, Cornelis A. M.', 'Haijema, Bert Jan', 'Boss, David', 'Heuts, Frank W. H.', 'Rottier, Peter J. M.']",,,,
,PMC,The Amino Terminus of Epstein-Barr Virus Glycoprotein gH Is Important for Fusion with Epithelial and B Cells,http://dx.doi.org/10.1128/JVI.79.19.12408-12415.2005,PMC1211543,,,"Epstein-Barr virus (EBV) infects B lymphocytes and epithelial cells. While the glycoproteins required for entry into these two cell types differ, the gH/gL glycoprotein complex is essential for entry into both epithelial and B cells. Analysis of gH protein sequences from three gammaherpesviruses (EBV, marmoset, and rhesus) revealed a potential coiled-coil domain in the N terminus. Four leucines located in this region in EBV gH were replaced by alanines by site-directed mutagenesis and analyzed for cell-cell membrane fusion with B cells and epithelial cells. Reduction in fusion activity was observed for mutants containing L65A and/or L69A mutations, while substitutions in L55 and L74 enhanced the fusion activity of the mutant gH/gL complexes with both cell types. All of the mutants displayed levels of cell surface expression similar to those of wild-type gH and interacted with gL and gp42. The observation that a conservative mutation of leucine to alanine in the N terminus of EBV gH results in fusion-defective mutant gH/gL complexes is striking and points to an important role for this region in EBV-mediated membrane fusion with B lymphocytes and epithelial cells.",,"['Omerović, Jasmina', 'Lev, Lori', 'Longnecker, Richard']",,,,
,PMC,Stem-Loop IV in the 5′ Untranslated Region Is a cis-Acting Element in Bovine Coronavirus Defective Interfering RNA Replication,http://dx.doi.org/10.1128/JVI.79.19.12434-12446.2005,PMC1211515,,,"The 210-nucleotide (nt) 5′ untranslated region (UTR) in the positive-strand bovine coronavirus (BCoV) genome is predicted to contain four higher-order structures identified as stem-loops I to IV, which may function as cis-acting elements in genomic RNA replication. Here, we describe evidence that stem-loop IV, a bulged stem-loop mapping at nt 186 through 215, (i) is phylogenetically conserved among group 2 coronaviruses and may have a homolog in groups 1 and 3, (ii) exists as a higher-order structure on the basis of enzyme probing, (iii) is required as a higher-order element for replication of a BCoV defective interfering (DI) RNA in the positive but not the negative strand, and (iv) as a higher-order structure in wild-type (wt) and mutant molecules that replicate, specifically binds six cellular proteins in the molecular mass range of 25 to 58 kDa as determined by electrophoretic mobility shift and UV cross-linking assays; binding to viral proteins was not detected. Interestingly, the predicted stem-loop IV homolog in the severe acute respiratory syndrome (SARS) coronavirus appears to be group 1-like in that it is in part duplicated with a group 1-like conserved loop sequence and is not group 2-like, as would be expected by the SARS coronavirus group 2-like 3′ UTR structure. These results together indicate that stem-loop IV in the BCoV 5′ UTR is a cis-acting element for DI RNA replication and that it might function through interactions with cellular proteins. It is postulated that stem-loop IV functions similarly in the virus genome.",,"['Raman, Sharmila', 'Brian, David A.']",,,,
,PMC,Managing severe acute respiratory syndrome (SARS) intellectual property rights: the possible role of patent pooling.,,PMC2626342,,,"Patent applications that incorporate the genomic sequence of the severe acute respiratory syndrome (SARS) coronavirus, have been filed by a number of organizations. This is likely to result in a fragmentation of intellectual property (IP) rights which in turn may adversely affect the development of products, such as vaccines, to combat SARS. Placing these patent rights into a patent pool to be licensed on a non-exclusive basis may circumvent these difficulties and set a key precedent for the use of this form of mechanism in other areas of health care, leading to benefits to public health.",,"['Simon, James H. M.', 'Claassen, Eric', 'Correa, Carmen E.', 'Osterhaus, Albert D. M. E.']",,,,
,PMC,The Heritage of Pathogen Pressures and Ancient Demography in the Human Innate-Immunity CD209/CD209L Region,,PMC1271393,,,"The innate immunity system constitutes the first line of host defense against pathogens. Two closely related innate immunity genes, CD209 and CD209L, are particularly interesting because they directly recognize a plethora of pathogens, including bacteria, viruses, and parasites. Both genes, which result from an ancient duplication, possess a neck region, made up of seven repeats of 23 amino acids each, known to play a major role in the pathogen-binding properties of these proteins. To explore the extent to which pathogens have exerted selective pressures on these innate immunity genes, we resequenced them in a group of samples from sub-Saharan Africa, Europe, and East Asia. Moreover, variation in the number of repeats of the neck region was defined in the entire Human Genome Diversity Panel for both genes. Our results, which are based on diversity levels, neutrality tests, population genetic distances, and neck-region length variation, provide genetic evidence that CD209 has been under a strong selective constraint that prevents accumulation of any amino acid changes, whereas CD209L variability has most likely been shaped by the action of balancing selection in non-African populations. In addition, our data point to the neck region as the functional target of such selective pressures: CD209 presents a constant size in the neck region populationwide, whereas CD209L presents an excess of length variation, particularly in non-African populations. An additional interesting observation came from the coalescent-based CD209 gene tree, whose binary topology and time depth (∼2.8 million years ago) are compatible with an ancestral population structure in Africa. Altogether, our study has revealed that even a short segment of the human genome can uncover an extraordinarily complex evolutionary history, including different pathogen pressures on host genes as well as traces of admixture among archaic hominid populations.",,"['Barreiro, Luis\xa0B.', 'Patin, Etienne', 'Neyrolles, Olivier', 'Cann, Howard\xa0M.', 'Gicquel, Brigitte', 'Quintana-Murci, Lluís']",,,,
,PMC,Development of nonhuman adenoviruses as vaccine vectors,http://dx.doi.org/10.1016/j.vaccine.2005.08.101,PMC1462960,,,"Human adenoviral (HAd) vectors have demonstrated great potential as vaccine vectors. Preclinical and clinical studies have demonstrated the feasibility of vector design, robust antigen expression and protective immunity using this system. However, clinical use of adenoviral vectors for vaccine purposes is anticipated to be limited by vector immunity that is either preexisting or develops rapidly following the first inoculation with adenoviral vectors. Vector immunity inactivates the vector particles and rapidly removes the transduced cells, thereby limiting the duration of transgene expression. Due to strong vector immunity, subsequent use of the same vector is usually less efficient. In order to circumvent this limitation, nonhuman adenoviral vectors have been proposed as alternative vectors. In addition to eluding HAd immunity, these vectors possess most of the attractive features of HAd vectors. Several replication-competent or replication-defective nonhuman adenoviral vectors have been developed and investigated for their potential as vaccine delivery vectors. Here, we review recent advances in the design and characterization of various nonhuman adenoviral vectors, and discuss their potential applications for human and animal vaccination.",,"['Bangari, Dinesh S.', 'Mittal, Suresh K.']",,,,
,PMC,Health information systems: the foundations of public health.,,PMC2626318,,,"Public health decision-making is critically dependent on the timely availability of sound data. The role of health information systems is to generate, analyse and disseminate such data. In practice, health information systems rarely function systematically. The products of historical, social and economic forces, they are complex, fragmented and unresponsive to needs. International donors in health are largely responsible for the problem, having prioritized urgent needs for data over longer-term country capacity-building. The result is painfully apparent in the inability of most countries to generate the data needed to monitor progress towards the Millennium Development Goals. Solutions to the problem must be comprehensive; money alone is likely to be insufficient unless accompanied by sustained support to country systems development coupled with greater donor accountability and allocation of responsibilities. The Health Metrics Network, a global collaboration in the making, is intended to help bring such solutions to the countries most in need.",,"['AbouZahr, Carla', 'Boerma, Ties']",,,,
,PMC,Harmonizing health information systems with information systems in other social and economic sectors.,,PMC2626316,,,"Efforts to strengthen health information systems in low- and middle-income countries should include forging links with systems in other social and economic sectors. Governments are seeking comprehensive socioeconomic data on the basis of which to implement strategies for poverty reduction and to monitor achievement of the Millennium Development Goals. The health sector is looking to take action on the social factors that determine health outcomes. But there are duplications and inconsistencies between sectors in the collection, reporting, storage and analysis of socioeconomic data. National offices of statistics give higher priority to collection and analysis of economic than to social statistics. The Report of the Commission for Africa has estimated that an additional US$ 60 million a year is needed to improve systems to collect and analyse statistics in Africa. Some donors recognize that such systems have been weakened by numerous international demands for indicators, and have pledged support for national initiatives to strengthen statistical systems, as well as sectoral information systems such as those in health and education. Many governments are working to coordinate information systems to monitor and evaluate poverty reduction strategies. There is therefore an opportunity for the health sector to collaborate with other sectors to lever international resources to rationalize definition and measurement of indicators common to several sectors; streamline the content, frequency and timing of household surveys; and harmonize national and subnational databases that store socioeconomic data. Without long-term commitment to improve training and build career structures for statisticians and information technicians working in the health and other sectors, improvements in information and statistical systems cannot be sustained.",,"Macfarlane, Sarah B.",,,,
,PMC,Structuring information and incentives to improve health.,,PMC2626310,,,,,"Stansfield, Sally",,,,
,PMC,World needs fresh research priorities and new policies to tackle changing patterns of chronic disease,,PMC1215589,,,,,"Mudur, Ganapati",,,,
,PMC,Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats,http://dx.doi.org/10.1073/pnas.0506735102,PMC1236580,,,"Although the finding of severe acute respiratory syndrome coronavirus (SARS-CoV) in caged palm civets from live animal markets in China has provided evidence for interspecies transmission in the genesis of the SARS epidemic, subsequent studies suggested that the civet may have served only as an amplification host for SARS-CoV. In a surveillance study for CoV in noncaged animals from the wild areas of the Hong Kong Special Administration Region, we identified a CoV closely related to SARS-CoV (bat-SARS-CoV) from 23 (39%) of 59 anal swabs of wild Chinese horseshoe bats (Rhinolophus sinicus) by using RT-PCR. Sequencing and analysis of three bat-SARS-CoV genomes from samples collected at different dates showed that bat-SARS-CoV is closely related to SARS-CoV from humans and civets. Phylogenetic analysis showed that bat-SARS-CoV formed a distinct cluster with SARS-CoV as group 2b CoV, distantly related to known group 2 CoV. Most differences between the bat-SARS-CoV and SARS-CoV genomes were observed in the spike genes, ORF 3 and ORF 8, which are the regions where most variations also were observed between human and civet SARS-CoV genomes. In addition, the presence of a 29-bp insertion in ORF 8 of bat-SARS-CoV genome, not in most human SARS-CoV genomes, suggests that it has a common ancestor with civet SARS-CoV. Antibody against recombinant bat-SARS-CoV nucleocapsid protein was detected in 84% of Chinese horseshoe bats by using an enzyme immunoassay. Neutralizing antibody to human SARS-CoV also was detected in bats with lower viral loads. Precautions should be exercised in the handling of these animals.",,"['Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Li, Kenneth S. M.', 'Huang, Yi', 'Tsoi, Hoi-Wah', 'Wong, Beatrice H. L.', 'Wong, Samson S. Y.', 'Leung, Suet-Yi', 'Chan, Kwok-Hung', 'Yuen, Kwok-Yung']",,,,
,PMC,"Environmental factors on the SARS epidemic: air temperature, passage of time and multiplicative effect of hospital infection",http://dx.doi.org/10.1017/S0950268805005054,PMC2870397,,,"The study sought to identify factors involved in the emergence, prevention and elimination of severe acute respiratory syndrome (SARS) in Hong Kong during 11 March to 22 May 2003. A structured multiphase regression analysis was used to estimate the potential effects of weather, time and interaction effect of hospital infection. In days with a lower air temperature during the epidemic, the risk of increased daily incidence of SARS was 18·18-fold (95% confidence interval 5·6–58·8) higher than in days with a higher temperature. The total daily new cases might naturally decrease by an average of 2·8 patients for every 10 days during the epidemic. The multiplicative effect of infected hospital staff with patients in an intensive care unit (ICU) and the proportion of SARS patients in ICUs might respectively increase the risk of a larger SARS epidemic in the community. The provision of protective gear in hospitals was also a very important factor for the prevention of SARS infection. SARS transmission appeared to be dependent on seasonal temperature changes and the multiplicative effect of hospital infection. SARS also appeared to retreat naturally over time.",,"['LIN, KUN', 'YEE-TAK FONG, DANIEL', 'ZHU, BILIU', 'KARLBERG, JOHAN']",,,,
,PMC,"Trends in Injuries, Illnesses, and Policies in Canadian Healthcare Workplaces",http://dx.doi.org/10.1007/BF03404026,PMC6976203,,,"BACKGROUND: Analysis of workers’ compensation data and occupational health and safety trends in healthcare across Canada was conducted to provide insight concerning workplace injuries and prevention measures undertaken in the healthcare sector. METHODS: Timeloss claims data were collected for 1992–2002 from the Association of Workers’ Compensation Boards of Canada. Labour Force data from Statistics Canada were used to calculate injury rates. The Occupational Health and Safety Agency for Healthcare in British Columbia coordinated with provincial occupational health and safety agencies in Ontario, Quebec and Nova Scotia to analyze injury data and collate prevention measures in their regions. RESULTS: The national timeloss injury rate declined from 4.3 to 3.7 injuries per 100 personyears since 1998. Musculoskeletal injuries consistently comprised the majority of timeloss claims. Needlestick injuries, infectious diseases and stress-related claims infrequently resulted in timeloss claims although they are known to cause great concern in the workplace. Prevention measures taken in the various provinces related to safer equipment (lifts and electric beds), return-to-work programs, and violence prevention initiatives. Different eligibility criteria as well as adjudication policies confounded the comparison of injury rates across provinces. DISCUSSION: Since 2000, all provinces experienced healthcare restructuring and increased workload in an aging workforce. Despite these increased risks, injury rates have decreased. Attribution for these trends is complex, but there is reason to believe that focus on prevention can further decrease injuries. While occupational health is a provincial jurisdiction, harmonizing data in addition to sharing data on successful prevention measures and best practices may improve workplace conditions and thereby further reduce injury rates for higher risk healthcare sector occupations.",,"['Yassi, Annalee', 'Gilbert, Mark', 'Cvitkovich, Yuri']",,,,
,PMC,Antibody to severe acute respiratory syndrome (SARS)-associated coronavirus spike protein domain 2 cross-reacts with lung epithelial cells and causes cytotoxicity,http://dx.doi.org/10.1111/j.1365-2249.2005.02864.x,PMC1809466,,,"Both viral effect and immune-mediated mechanism are involved in the pathogenesis of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infection. In this study, we showed that in SARS patient sera there were autoantibodies (autoAbs) that reacted with A549 cells, the type-2 pneumocytes, and that these autoAbs were mainly IgG. The autoAbs were detectable 20 days after fever onset. Tests of non-SARS-pneumonia patients did not show the same autoAb production as in SARS patients. After sera IgG bound to A549 cells, cytotoxicity was induced. Cell cytotoxicity and the anti-epithelial cell IgG level were positively correlated. Preabsorption and binding assays indicated the existence of cross-reactive epitopes on SARS-CoV spike protein domain 2 (S2). Furthermore, treatment of A549 cells with anti-S2 Abs and IFN-γ resulted in an increase in the adherence of human peripheral blood mononuclear cells to these epithelial cells. Taken together, we have demonstrated that the anti-S2 Abs in SARS patient sera cause cytotoxic injury as well as enhance immune cell adhesion to epithelial cells. The onset of autoimmune responses in SARS-CoV infection may be implicated in SARS pathogenesis.",,"['Lin, Y S', 'Lin, C F', 'Fang, Y T', 'Kuo, Y M', 'Liao, P C', 'Yeh, T M', 'Hwa, K Y', 'Shieh, C C K', 'Yen, J H', 'Wang, H J', 'Su, I J', 'Lei, H Y']",,,,
,PMC,Author index,http://dx.doi.org/10.1111/j.1365-2249.2005.02899.x,PMC1809460,,,,,,,,,
,PMC,LEW.1WR1 RATS DEVELOP AUTOIMMUNE DIABETES SPONTANEOUSLY AND IN RESPONSE TO ENVIRONMENTAL PERTURBATION,,PMC1283095,,,"We describe a new rat model of autoimmune diabetes that arose in a major histocompatibility complex (MHC) congenic LEW rat. Spontaneous diabetes in LEW.1WR1 rats (RT1(u/u/a)) occurs with a cumulative frequency of ∼2% at a median age of 59 days. The disease is characterized by hyperglycemia, glycosuria, ketonuria and polyuria. Both sexes are affected, and islets of acutely diabetic rats are devoid of beta cells whereas alpha and delta cell populations are spared. The peripheral lymphoid phenotype is normal, including the fraction of ART2(+) regulatory T cells (Tregs). We tested the hypothesis that the expression of diabetes would be increased by immunological perturbation of innate or adaptive immunity. Treatment of young rats with depleting anti-ART2.1 mAb increased the frequency of diabetes to 50%. Treatment with the toll-like receptor 3 (TLR3) ligand polyinosinic:polycytidylic acid increased the frequency of diabetes to 100%. All diabetic rats exhibited end-stage islets. The LEW.1WR1 rat is also susceptible to collagen-induced arthritis but is free of spontaneous thyroiditis. The LEW.1WR1 rat provides a new model for studying autoimmune diabetes and arthritis in an animal with a genetic predisposition to both disorders that can be amplified by environmental perturbation.",,"['Mordes, John P.', 'Guberski, Dennis L.', 'Leif, Jean H.', 'Woda, Bruce A.', 'Flanagan, Joan F.', 'Greiner, Dale L.', 'Kislauskis, Edward H.', 'Tirabassi, Rebecca S.']",,,,
,PMC,"Advocacy, promotion and e-learning: Supercourse for zoonosis",http://dx.doi.org/10.1007/BF02897702,PMC2723411,,,"This paper discusses the history of emerging infectious diseases, risk communication and perception, and the Supercourse lectures as means to strengthen the concepts and definition of risk management and global governance of zoonosis. The paper begins by outlining some of the key themes and issues in infectious diseases, highlighting the way which historical analysis challenges ideas of the ‘newness’ of some of these developments. It then discusses the role of risk communication to public accountability. The bulk of the paper presents an overview of developments of the Internet-based learning system through the Supercourse lectures that may prove to be a strong arm for the promotion of the latest medical information particularly to developing countries.",,"['Matibag, Gino C.', 'Igarashi, Manabu', 'La Porte, Ron E.', 'Tamashiro, Hiko']",,,,
,PMC,Control of Severe Acute Respiratory Syndrome in Singapore,http://dx.doi.org/10.1007/BF02897699,PMC2723408,,,"A Severe Acute Respiratory Syndrome (SARS) outbreak occurred in Singapore from February to May 2003. A high vigilance for the disease, frequent and regular temperature monitoring, early case identification and isolation of patients, as well as tracing and home quarantine of contacts, played major roles in controlling the outbreak. Hospitals were dedicated to the screening and treatment of SARS patients. Within and between hospitals, movement by healthcare workers, patients and visitors were restricted, as was the number of hospital visitors. Staff education and audits of infection control practices also featured prominently. To prevent cross-border transmission, incoming travellers from SARS affected areas had to complete health declaration cards. They, as well as all outgoing travellers from Singapore, were monitored for fever. In the meantime, the public was urged to refrain from travelling to SARS affected regions. Containment elements targeting the community included school closure, public education on good hygiene and readily accessible public information. In response to a laboratory acquired SARS infection, laboratories were audited, and directives issued on the mandatory use of biosafety level 3 laboratories for SARS virus culture, and compliance of laboratory workers to biosafety guidelines.",,"Chan, Kwai Pen",,,,
,PMC,Lessons learned from international responses to severe acute respiratory syndrome (SARS),http://dx.doi.org/10.1007/BF02897698,PMC2723407,,,"In early February 2003, a previously unknown disease causing severe pneumonia was recognised. This disease which is now known as severe acute respiratory syndrome (SARS) is believed to have had its origins in the Guangdong Province of China, and was the cause of a multi-country epidemic resulting in significant morbidity and mortality. The World Health Organization (WHO) has been coordinating the international response to provide the epidemiological, laboratory, clinical and logistic requirements needed to contain this disease. A rapid spread of SARS around the world occurred at its onset, facilitated greatly by air travel. Between November 2002 and July 2003, a total of 8,094 cases and 774 cases were reported from 26 countries worldwide. WHO responded quickly to this multi-country outbreak and on 12 March released a “global alert” about SARS. This was followed by the first WHO travel advisory on 15 March. The Global Outbreak Alert and Response Network was activated, and international experts were brought together to implement enhanced global surveillance systems for SARS. The international community has learned a lot of lessons from the SARS outbreak. Particularly, rapid and transparent information sharing between countries is critical to prevent international spread of the disease. However, information exchange was less than optimal in the early phase of the outbreak.",,"Oshitani, Hitoshi",,,,
,PMC,The Clinical Presentation and Outcomes of Children Infected with Newly Identified Respiratory Tract Viruses,http://dx.doi.org/10.1016/j.idc.2005.05.009,PMC3351010,,,,,"Williams, John V.",,,,
,PMC,Human Coronavirus NL-63 Infections in Children: a 1-Year Study,http://dx.doi.org/10.1128/JCM.43.9.4567-4573.2005,PMC1234132,,,"Human coronavirus NL63 (HCoV-NL63), a newly discovered coronavirus, has been associated with acute respiratory tract infections (ARI). Important questions pertaining to the contribution of HCoV-NL63 to ARI and its impact on public health remain. We reviewed HCoV-NL63 in specimens collected from 13 November 2002 to 31 December 2003 from the Stollery Children's Hospital on patients of <17 years of age to assess the role of this virus in ARI in children. Twenty-six of 1,240 specimens (2.1%) from seven outpatients and 19 inpatients aged 7 days to 9.5 years tested positive for HCoV-NL63 by reverse transcription-PCR. The majority of outpatients (86%) had upper respiratory tract infections, while the majority of inpatients (58%) had bronchiolitis. Peak HCoV-NL63 activity occurred in March. These results provide further evidence of the importance of HCoV-NL63 in ARI in children.",,"['Bastien, Nathalie', 'Robinson, Joan L.', 'Tse, Alena', 'Lee, Bonita E.', 'Hart, Laura', 'Li, Yan']",,,,
,PMC,Human Parainfluenza Virus 4 Outbreak and the Role of Diagnostic Tests,http://dx.doi.org/10.1128/JCM.43.9.4515-4521.2005,PMC1234116,,,"Owing to the difficulties in isolating the virus and the lack of routine surveillance, the clinical significance of human parainfluenza virus 4 (HPIV-4) is less well defined than that of the other human parainfluenza viruses. We describe the first outbreak of HPIV-4 infection in a developmental disabilities unit, involving 38 institutionalized children and three staff members, during a 3-week period in autumn 2004. Most subjects had upper respiratory tract infections (URTI), while lower respiratory tract infections (LRTI) occurred in three children (7%), one complicated by respiratory failure requiring ventilation support. All patients recovered. Nasopharyngeal aspirates tested for HPIV-4 were positive by reverse transcriptase PCR (RT-PCR) in all 41 cases (100%), by direct immunofluorescence in 29 of 39 tested cases (74%), and by cell cultures in 6 of 37 cases (16%), and serum was positive for antibodies against HPIV-4 in all 35 cases (100%) with serum samples available. In addition, RT-PCR detected HPIV-4 in four children (three LRTI and one URTI) out of 115 patients with community-acquired respiratory tract infection. Molecular analysis of the 1,198-bp phosphoprotein sequences showed that HPIV-4 isolates among the cases were genetically similar, whereas the community controls were more genetically distant, supporting nosocomial transmission of a single HPIV-4 genotype during the outbreak. Moreover, the HPIV-4 causing the outbreak is more closely related to HPIV-4A than HPIV-4B. HPIV-4 may be an important cause of more severe respiratory illness in children. The present RT-PCR assay is a sensitive, specific, and rapid method for the diagnosing HPIV-4 infection. To better define the epidemiology and clinical spectrum of disease of HPIV-4 infections, HPIV-4 should be included in the routine panels of respiratory virus detection on respiratory specimens.",,"['Lau, Susanna K. P.', 'To, Wing-kin', 'Tse, Philomena W. T.', 'Chan, Alex K. H.', 'Woo, Patrick C. Y.', 'Tsoi, Hoi-wah', 'Leung, Annie F. Y.', 'Li, Kenneth S. M.', 'Chan, Paul K. S.', 'Lim, Wilina W. L.', 'Yung, Raymond W. H.', 'Chan, Kwok-hung', 'Yuen, Kwok-yung']",,,,
,PMC,Interferon-β and interferon-γ synergize to block viral DNA and virion synthesis in herpes simplex virus-infected cells.,http://dx.doi.org/10.1099/vir.0.80979-0,PMC1366490,,,"The capacity of herpes simplex virus type 1 (HSV-1) to replicate in vitro decreases tremendously when animal cell cultures are exposed to ligands of both the interferon (IFN)-α/β receptor and IFN-γ receptor prior to inoculation with low MOIs of HSV-1. However, the available evidence provides no insight into the possible mechanisms by which co-activation of the IFN-α/β- and IFN-γ-signaling pathways produces this effect. Therefore, it has not been possible to differentiate whether these observations represent an important in vitro model of host immunological suppression of HSV-1 infection, or an irrelevant laboratory phenomenon. Therefore, the current study was initiated to determine if co-activation of the host cell’s IFN-α/β and IFN-γ pathways either (a) induces death of HSV-1 infected cells such that viral replication is unable to occur or (b) disrupts one or more steps in the process of HSV-1 replication. To this end, multiple steps in HSV-1 infection were compared in populations of Vero cells infected with HSV-1 strain KOS (MOI=2.5) and exposed to ligands of the 1. IFN-α/β receptor, 2. IFN-γ receptor, or 3. both the IFN-α/β receptor and IFN-γ receptor. The results demonstrate that IFN-β and IFN-γ interact in a synergistic manner to block the efficient synthesis of viral DNA and nucleocapsid formation in HSV-1 infected cells, and do so without adversely affecting host cell viability. We infer that IFN-mediated suppression of HSV-1 replication may be a central mechanism by which the host immune system limits the spread of HSV-1 infection in vivo.",,"['Pierce, Amy T.', 'DeSalvo, Joanna', 'Foster, Timothy P.', 'Kosinski, Athena', 'Weller, Sandra K.', 'Halford., William P.']",,,,
,PMC,Single Amino Acid Substitutions in the Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Determine Viral Entry and Immunogenicity of a Major Neutralizing Domain,http://dx.doi.org/10.1128/JVI.79.18.11638-11646.2005,PMC1212612,,,"Neutralizing antibodies (NAbs) against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) spike (S) glycoprotein confer protection to animals experimentally infected with the pathogenic virus. We and others previously demonstrated that a major mechanism for neutralizing SARS-CoV was through blocking the interaction between the S glycoprotein and the cellular receptor angiotensin-converting enzyme 2 (ACE2). In this study, we used in vivo electroporation DNA immunization and a pseudovirus-based assay to functionally evaluate immunogenicity and viral entry. We characterized the neutralization and viral entry determinants within the ACE2-binding domain of the S glycoprotein. The deletion of a positively charged region SΔ(422-463) abolished the capacity of the S glycoprotein to induce NAbs in mice vaccinated by in vivo DNA electroporation. Moreover, the SΔ(422-463) pseudovirus was unable to infect HEK293T-ACE2 cells. To determine the specific residues that contribute to related phenotypes, we replaced eight basic amino acids with alanine. We found that a single amino acid substitution (R441A) in the full-length S DNA vaccine failed to induce NAbs and abolished viral entry when pseudoviruses were generated. However, another substitution (R453A) abolished viral entry while retaining the capacity for inducing NAbs. The difference between R441A and R453A suggests that the determinants for immunogenicity and viral entry may not be identical. Our findings provide direct evidence that these basic residues are essential for immunogenicity of the major neutralizing domain and for viral entry. Our data have implications for the rational design of vaccine and antiviral agents as well as for understanding viral tropism.",,"['Yi, Christopher E.', 'Ba, Lei', 'Zhang, Linqi', 'Ho, David D.', 'Chen, Zhiwei']",,,,
,PMC,Molecular Evolution Analysis and Geographic Investigation of Severe Acute Respiratory Syndrome Coronavirus-Like Virus in Palm Civets at an Animal Market and on Farms,http://dx.doi.org/10.1128/JVI.79.18.11892-11900.2005,PMC1212604,,,"Massive numbers of palm civets were culled to remove sources for the reemergence of severe acute respiratory syndrome (SARS) in Guangdong Province, China, in January 2004, following SARS coronavirus detection in market animals. The virus was identified in all 91 palm civets and 15 raccoon dogs of animal market origin sampled prior to culling, but not in 1,107 palm civets later sampled at 25 farms, spread over 12 provinces, which were claimed to be the source of traded animals. Twenty-seven novel signature variation residues (SNVs) were identified on the spike gene and were analyzed for their phylogenetic relationships, based on 17 sequences obtained from animals in our study and from other published studies. Analysis indicated that the virus in palm civets at the live-animal market had evolved to infect humans. The evolutionary starting point was a prototype group consisting of three viral sequences of animal origin. Initially, seven SNV sites caused six amino acid changes, at positions 147, 228, 240, 479, 821, and 1080 of the spike protein, to generate low-pathogenicity viruses. One of these was linked to the first SARS patient in the 2003-2004 period. A further 14 SNVs caused 11 amino acid residue changes, at positions 360, 462, 472, 480, 487, 609, 613, 665, 743, 765, and 1163. The resulting high-pathogenicity groups were responsible for infections during the so-called early-phase epidemic of 2003. Finally, the remaining six SNVs caused four amino acid changes, at positions 227, 244, 344, and 778, which resulted in the group of viruses responsible for the global epidemic.",,"['Kan, Biao', 'Wang, Ming', 'Jing, Huaiqi', 'Xu, Huifang', 'Jiang, Xiugao', 'Yan, Meiying', 'Liang, Weili', 'Zheng, Han', 'Wan, Kanglin', 'Liu, Qiyong', 'Cui, Buyun', 'Xu, Yanmei', 'Zhang, Enmin', 'Wang, Hongxia', 'Ye, Jingrong', 'Li, Guichang', 'Li, Machao', 'Cui, Zhigang', 'Qi, Xiaobao', 'Chen, Kai', 'Du, Lin', 'Gao, Kai', 'Zhao, Yu-teng', 'Zou, Xiao-zhong', 'Feng, Yue-Ju', 'Gao, Yu-Fan', 'Hai, Rong', 'Yu, Dongzhen', 'Guan, Yi', 'Xu, Jianguo']",,,,
,PMC,Activity of the Mason-Pfizer Monkey Virus Fusion Protein Is Modulated by Single Amino Acids in the Cytoplasmic Tail,http://dx.doi.org/10.1128/JVI.79.18.11569-11579.2005,PMC1212599,,,"Mason-Pfizer monkey virus (M-PMV) encodes a transmembrane glycoprotein with a 38-amino-acid-long cytoplasmic tail. After the release of the immature virus, a viral protease-mediated cleavage of the cytoplasmic tail (CT) results in the loss of 17 amino acids from the carboxy terminus and renders the envelope protein fusion competent. To investigate the role of individual amino acid residues in the CT in fusion, a series of mutations was introduced, and the effects of these mutations on glycoprotein biosynthesis and fusion were examined. Most of the alanine-scanning mutations in the CT had little effect on fusion activity. However, four amino acid substitutions (threonine 4, lysine 7, glutamine 9, and isoleucine 10) resulted in substantially increased fusogenicity, while six (leucine 2, phenylalanine 5, isoleucine 13, lysine 16, proline 17, and glycine 31) resulted in much-reduced fusion. Interestingly, the bulk of these mutations are located upstream of the CT cleavage site in a region that has the potential to form a coiled-coil in the Env trimer. Substitutions at glutamine 9 and isoleucine 10 with alanine had the most dramatic positive effect and resulted in the formation of large syncytia. Taken together, these data demonstrate that individual residues within the cytoplasmic domain of M-PMV Env can modulate, in both a positive and negative manner, biological functions that are associated with the extracellular domains of the glycoprotein complex.",,"['Song, Chisu', 'Micoli, Keith', 'Hunter, Eric']",,,,
,PMC,The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein Is Phosphorylated and Localizes in the Cytoplasm by 14-3-3-Mediated Translocation,http://dx.doi.org/10.1128/JVI.79.17.11476-11486.2005,PMC1193639,,,"The severe acute respiratory syndrome coronavirus(SARS-CoV) nucleocapsid (N) protein is one of the four structural proteins of the virus and is predicted to be a 46-kDa phosphoprotein. Our in silico analysis predicted N to be heavily phosphorylated at multiple residues. Experimentally, we have shown in this report that the N protein of the SARS-CoV gets serine-phosphorylated by multiple kinases, in both the cytoplasm and the nucleus. The phosphoprotein is stable and localizes in the cytoplasm and coprecipitates with the membrane fraction. Also, using specific inhibitors of phosphorylation and an in vitro phosphorylation assay, we show that the nucleocapsid protein is a substrate of cyclin-dependent kinase (CDK), glycogen synthase kinase, mitogen-activated protein kinase, and casein kinase II. Further, we show that the phosphorylated protein is translocated to the cytoplasm by binding to 14-3-3 (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein). 14-3-3 proteins are a family of highly conserved, ubiquitously expressed eukaryotic proteins that function primarily as adapters that modulate interactions between components of various cellular signaling and cell cycle regulatory pathways through phosphorylation-dependent protein-protein interactions. Coincidentally, the N protein was also found to downregulate the expression of the theta isoform of 14-3-3 (14-3-3θ), leading to the accumulation of phosphorylated N protein in the nucleus, in the absence of growth factors. Using short interfering RNA specific to 14-3-3θ we have inhibited its expression to show accumulation of phosphorylated N protein in the nucleus. Thus, the data presented here provide a possible mechanism for phosphorylation-dependent nucleocytoplasmic shuttling of the N protein. This 14-3-3-mediated transport of the phosphorylated N protein and its possible implications in interfering with the cellular machinery are discussed.",,"['Surjit, Milan', 'Kumar, Ravinder', 'Mishra, Rabi N.', 'Reddy, Malireddy K.', 'Chow, Vincent T. K.', 'Lal, Sunil K.']",,,,
,PMC,A Severe Acute Respiratory Syndrome-Associated Coronavirus-Specific Protein Enhances Virulence of an Attenuated Murine Coronavirus,http://dx.doi.org/10.1128/JVI.79.17.11335-11342.2005,PMC1193615,,,"Most animal species that can be infected with the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) do not reproducibly develop clinical disease, hindering studies of pathogenesis. To develop an alternative system for the study of SARS-CoV, we introduced individual SARS-CoV genes (open reading frames [ORFs]) into the genome of an attenuated murine coronavirus. One protein, the product of SARS-CoV ORF6, converted a sublethal infection to a uniformly lethal encephalitis and enhanced virus growth in tissue culture cells, indicating that SARS-CoV proteins function in the context of a heterologous coronavirus infection. Furthermore, these results suggest that the attenuated murine coronavirus lacks a virulence gene residing in SARS-CoV. Recombinant murine coronaviruses cause a reproducible and well-characterized clinical disease, offer virtually no risk to laboratory personnel, and should be useful for elucidating the role of SARS-CoV nonstructural proteins in viral replication and pathogenesis.",,"['Pewe, Lecia', 'Zhou, Haixia', 'Netland, Jason', 'Tangudu, Chandra', 'Olivares, Heidi', 'Shi, Lei', 'Look, Dwight', 'Gallagher, Thomas', 'Perlman, Stanley']",,,,
,PMC,Intracellular Localization of the Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein: Absence of Nucleolar Accumulation during Infection and after Expression as a Recombinant Protein in Vero Cells,http://dx.doi.org/10.1128/JVI.79.17.11507-11512.2005,PMC1193611,,,"The nucleocapsid (N) protein of several members within the order Nidovirales localizes to the nucleolus during infection and after transfection of cells with N genes. However, confocal microscopy of N protein localization in Vero cells infected with the severe acute respiratory syndrome coronavirus (SARS-CoV) or transfected with the SARS-CoV N gene failed to show the presence of N in the nucleoplasm or nucleolus. Amino acids 369 to 389, which contain putative nuclear localization signal (NLS) and nucleolar localization signal motifs, failed to restore nuclear localization to an NLS-minus mutant Rev protein. These data indicate that nuclear localization is not a conserved property among all nidoviruses.",,"['Rowland, Raymond R. R.', 'Chauhan, Vinita', 'Fang, Ying', 'Pekosz, Andrew', 'Kerrigan, Maureen', 'Burton, Miriam D.']",,,,
,PMC,"The Cotton Rat (Sigmodon hispidus) Is a Permissive Small Animal Model of Human Metapneumovirus Infection, Pathogenesis, and Protective Immunity",http://dx.doi.org/10.1128/JVI.79.17.10944-10951.2005,PMC1193579,,,"Human metapneumovirus (hMPV) is a newly described paramyxovirus that is an important cause of acute respiratory tract disease. We undertook to develop a small animal model of hMPV infection, pathogenesis, and protection. Hamsters, guinea pigs, cotton rats, and nine inbred strains of mice were inoculated intranasally with hMPV. The animals were sacrificed, and nasal and lung tissue virus yields were determined by plaque titration. None of the animals exhibited respiratory symptoms. The quantity of virus present in the nasal tissue ranged from 4.6 × 10(2) PFU/gram tissue (C3H mice) to greater than 10(5) PFU/gram (hamster). The amount of virus in the lungs was considerably less than in nasal tissue in each species tested, ranging from undetectable (<5 PFU/g; guinea pigs) to 1.8 × 10(5) PFU/gram (cotton rat). The peak virus titer in cotton rat lungs occurred on day 4 postinfection. hMPV-infected cotton rat lungs examined on day 4 postinfection exhibited histopathological changes consisting of peribronchial inflammatory infiltrates. Immunohistochemical staining detected virus only at the luminal surfaces of respiratory epithelial cells throughout the respiratory tract. hMPV-infected cotton rats mounted virus-neutralizing antibody responses and were partially protected against virus shedding and lung pathology on subsequent rechallenge with hMPV. Viral antigen was undetectable in the lungs on challenge of previously infected animals. This study demonstrates that the cotton rat is a permissive small animal model of hMPV infection that exhibits lung histopathology associated with infection and that primary infection protected animals against subsequent infection. This model will allow further in vivo studies of hMPV pathogenesis and evaluation of vaccine candidates.",,"['Williams, John V.', 'Tollefson, Sharon J.', 'Johnson, Joyce E.', 'Crowe, James E.']",,,,
,PMC,RNA Interference-Mediated Virus Clearance from Cells both Acutely and Chronically Infected with the Prototypic Arenavirus Lymphocytic Choriomeningitis Virus,http://dx.doi.org/10.1128/JVI.79.17.11071-11081.2005,PMC1193575,,,"Several arenaviruses, including Lassa fever virus, cause severe, often lethal hemorrhagic fever in humans. No licensed vaccines are available in the United States, and currently there is no efficacious therapy to treat this viral infection. Therefore the importance of developing effective antiviral approaches to combat pathogenic arenaviruses is clear. Moreover, the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is an important model for the study of viral persistence and associated diseases, as well as for exploring therapies to treat viral chronic infections. The use of small interfering RNAs (siRNAs) to downregulate gene expression via RNA interference (RNAi) has emerged as a powerful genetic tool for the study of gene function. In addition, the successful use of siRNAs to target a variety of animal viruses has led us to consider RNAi as a potential novel antiviral strategy. We have investigated the use of RNAi therapy against LCMV. Here, we show that siRNAs targeting sequences within the viral L polymerase and Z mRNAs inhibit LCMV multiplication in cultured cells. Unexpectedly, the antiviral efficacy of RNAi-based therapy against LCMV was highly dependent on the method used to deliver effector siRNA molecules. Thus, transfection of chemically synthesized siRNA pools to L and Z was ineffective in preventing virus multiplication. In contrast, targeting of the same viral L and Z gene products with siRNAs produced inside cells using a replication-deficient recombinant adenovirus expression system inhibited LCMV multiplication very efficiently. Notably, transduction with the replication-deficient recombinant adenovirus expression system to Z and L effectively cured persistently LCMV-infected cells, suggesting the feasibility of using RNAi therapy to combat viral chronic infections by riboviruses.",,"['Sánchez, Ana B.', 'Perez, Mar', 'Cornu, Tatjana', 'de la Torre, Juan Carlos']",,,,
,PMC,Assuring public health professionals are prepared for the future: the UAB public health integrated core curriculum.,,PMC1497761,,,"In response to calls to improve public health education and our own desire to provide a more relevant educational experience to our Master of Public Health students, the University of Alabama at Birmingham (UAB) School of Public Health designed, developed, and instituted a fully integrated public health core curriculum in the fall of 2001. This curriculum combines content from discipline-specific courses in biostatistics, environmental health, epidemiology, health administration, and the social and behavioral sciences, and delivers it in a 15 credit hour, team-taught course designed in modules covering such topics as tobacco, infectious diseases, and emergency preparedness. Weekly skills-building sessions increase student competence in data analysis and interpretation, communication, ethical decision-making, community-based interventions, and policy and program planning. Evaluations affirm that the integrated core is functioning as intended: as a means to provide critical content in the core disciplines in their applied context. As public health education continues to be debated, the UAB public health integrated core curriculum can serve as one model for providing quality instruction that is highly relevant to professional practice.",,"['Petersen, Donna J.', 'Hovinga, Mary E.', 'Pass, Mary Ann', 'Kohler, Connie', 'Oestenstad, R. Kent', 'Katholi, Charles']",,,,
,PMC,A review of instruments assessing public health preparedness.,,PMC1497752,,,"OBJECTIVES: The purpose of this study was to review instruments that assess the level of preparedness of state and local public health departments to respond to health threats such as bioterrorism. METHODS: The authors examined 27 published population-based instruments for planning or evaluating preparedness that were mostly unavailable in the peer-reviewed literature. Using the Essential Public Health Services framework, the instruments were evaluated for (1) clarity of measurement parameters, (2) balance between structural and process measures, (3) evidence of effectiveness, and (4) specification of an accountable entity. RESULTS: There was a great deal of overlap but little consistency in what constitutes ""preparedness"" or how it should be measured. Most instruments relied excessively on subjective or structural measures, lacked scientific evidence for measures assessed, and failed to clearly define what entity was accountable for accomplishing the task or function. CONCLUSION: Strategies for improvement include measure standardization, better interagency communication, and investment in public health practice research to develop the underlying evidence base required for developing quality measures and assessments.",,"['Asch, Steven M.', 'Stoto, Michael', 'Mendes, Marc', 'Valdez, R. Burciaga', 'Gallagher, Meghan E.', 'Halverson, Paul', 'Lurie, Nicole']",,,,
,PMC,Gene expression profiles in peripheral blood mononuclear cells of SARS patients,http://dx.doi.org/10.3748/wjg.v11.i32.5037,PMC4321926,,,"AIM: To investigate the role of inflammatory and anti-viral genes in the pathogenesis of SARS. METHODS: cDNA microarrays were used to screen the gene expression profiles of peripheral blood mononuclear cells (PBMCs) in two SARS patients (one in the acute severe phase and the other in the convalescent phase) and a healthy donor. In addition, real-time qualitative PCR was also performed to verify the reproducibility of the microarray results. The data were further analyzed. RESULTS: Many inflammatory and anti-viral genes were differentially expressed in SARS patients. Compared to the healthy control or the convalescent case, plenty of pro-inflammatory cytokines such as IL-1, TNF-α, IL-8, and MAPK signaling pathway were significantly upregulated in the acute severe case. However, anti-inflammatory agents such as IL-4 receptor, IL-13 receptor, IL-1Ra, and TNF-α-induced proteins 3 and 6 also increased dramatically in the acute severe case. On the contrary, a lot of IFN-stimulated genes like PKR, GBP-1 and 2, CXCL-10 and 11, and JAK/STAT signal pathway were downregulated in the acute severe case compared to the convalescent case. CONCLUSION: Gene expression in SARS patients mirrors a host state of inflammation and anti-viral immunity at the transcription level, and understanding of gene expression profiles may make contribution to further studies of the SARS pathogenesis.",,"['Yu, Shi-Yan', 'Hu, Yun-Wen', 'Liu, Xiao-Ying', 'Xiong, Wei', 'Zhou, Zhi-Tong', 'Yuan, Zheng-Hong']",,,,
,PMC,Infectious disease control using contact tracing in random and scale-free networks,http://dx.doi.org/10.1098/rsif.2005.0079,PMC1618487,,,"Contact tracing aims to identify and isolate individuals that have been in contact with infectious individuals. The efficacy of contact tracing and the hierarchy of traced nodes—nodes with higher degree traced first—is investigated and compared on random and scale-free (SF) networks with the same number of nodes N and average connection K. For values of the transmission rate larger than a threshold, the final epidemic size on SF networks is smaller than that on corresponding random networks. While in random networks new infectious and traced nodes from all classes have similar average degrees, in SF networks the average degree of nodes that are in more advanced stages of the disease is higher at any given time. On SF networks tracing removes possible sources of infection with high average degree. However a higher tracing effort is required to control the epidemic than on corresponding random networks due to the high initial velocity of spread towards the highly connected nodes. An increased latency period fails to significantly improve contact tracing efficacy. Contact tracing has a limited effect if the removal rate of susceptible nodes is relatively high, due to the fast local depletion of susceptible nodes.",,"['Kiss, Istvan Z', 'Green, Darren M', 'Kao, Rowland R']",,,,
,PMC,A loop 2 cytidine-stem 1 minor groove interaction as a positive determinant for pseudoknot-stimulated –1 ribosomal frameshifting,http://dx.doi.org/10.1073/pnas.0506166102,PMC1200304,,,"The molecular determinants of stimulation of –1 programmed ribosomal frameshifting (–1 PRF) by RNA pseudoknots are poorly understood. Sugarcane yellow leaf virus (ScYLV) encodes a 28-nt mRNA pseudoknot that promotes –1 PRF between the P1 (protease) and P2 (polymerase) genes in plant luteoviruses. The solution structure of the ScYLV pseudoknot reveals a well ordered loop 2 (L2) that exhibits continuous stacking of A20 through C27 in the minor groove of the upper stem 1 (S1), with C25 flipped out of the triple-stranded stack. Five consecutive triple base pairs flank the helical junction where the 3′ nucleotide of L2, C27, adopts a cytidine 27 N3-cytidine 14 2′-OH hydrogen bonding interaction with the C14-G7 base pair. This interaction is isosteric with the adenosine N1–2′-OH interaction in the related mRNA from beet western yellows virus (BWYV); however, the ScYLV and BWYV mRNA structures differ in their detailed L2–S1 hydrogen bonding and L2 stacking interactions. Functional analyses of ScYLV/BWYV chimeric pseudoknots reveal that the ScYLV RNA stimulates a higher level of –1 PRF (15 ± 2%) relative to the BWYV pseudoknot (6 ± 1%), a difference traced largely to the identity of the 3′ nucleotide of L2 (C27 vs. A25 in BWYV). Strikingly, C27A ScYLV RNA is a poor frameshift stimulator (2.0%) and is destabilized by ≈1.5 kcal·mol(–1) (pH 7.0, 37°C) with respect to the wild-type pseudoknot. These studies establish that the precise network of weak interactions nearest the helical junction in structurally similar pseudoknots make an important contribution to setting the frameshift efficiency in mRNAs.",,"['Cornish, Peter V.', 'Hennig, Mirko', 'Giedroc, David P.']",,,,
,PMC,Cloning of a human parvovirus by molecular screening of respiratory tract samples,http://dx.doi.org/10.1073/pnas.0504666102,PMC1200281,,,"The identification of new virus species is a key issue for the study of infectious disease but is technically very difficult. We developed a system for large-scale molecular virus screening of clinical samples based on host DNA depletion, random PCR amplification, large-scale sequencing, and bioinformatics. The technology was applied to pooled human respiratory tract samples. The first experiments detected seven human virus species without the use of any specific reagent. Among the detected viruses were one coronavirus and one parvovirus, both of which were at that time uncharacterized. The parvovirus, provisionally named human bocavirus, was in a retrospective clinical study detected in 17 additional patients and associated with lower respiratory tract infections in children. The molecular virus screening procedure provides a general culture-independent solution to the problem of detecting unknown virus species in single or pooled samples. We suggest that a systematic exploration of the viruses that infect humans, “the human virome,” can be initiated.",,"['Allander, Tobias', 'Tammi, Martti T.', 'Eriksson, Margareta', 'Bjerkner, Annelie', 'Tiveljung-Lindell, Annika', 'Andersson, Björn']",,,,
,PMC,Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection,http://dx.doi.org/10.1073/pnas.0503203102,PMC1194915,,,"A unique coronavirus severe acute respiratory syndrome-coronavirus (SARS-CoV) was revealed to be a causative agent of a life-threatening SARS. Although this virus grows in a variety of tissues that express its receptor, the mechanism of the severe respiratory illness caused by this virus is not well understood. Here, we report a possible mechanism for the extensive damage seen in the major target organs for this disease. A recent study of the cell entry mechanism of SARS-CoV reveals that it takes an endosomal pathway. We found that proteases such as trypsin and thermolysin enabled SARS-CoV adsorbed onto the cell surface to enter cells directly from that site. This finding shows that SARS-CoV has the potential to take two distinct pathways for cell entry, depending on the presence of proteases in the environment. Moreover, the protease-mediated entry facilitated a 100- to 1,000-fold higher efficient infection than did the endosomal pathway used in the absence of proteases. These results suggest that the proteases produced in the lungs by inflammatory cells are responsible for high multiplication of SARS-CoV, which results in severe lung tissue damage. Likewise, elastase, a major protease produced in the lungs during inflammation, also enhanced SARS-CoV infection in cultured cells.",,"['Matsuyama, Shutoku', 'Ujike, Makoto', 'Morikawa, Shigeru', 'Tashiro, Masato', 'Taguchi, Fumihiro']",,,,
,PMC,,,PMC1188130,,,,,,,,,
,PMC,"H5N1 influenza and the implications for Europe: A pandemic is likely, but Europe is getting prepared",,PMC1188095,,,,,"['Coulombier, Denis', 'Ekdahl, Karl']",,,,
,PMC,Glial grafting for demyelinating disease,http://dx.doi.org/10.1098/rstb.2005.1700,PMC1569542,,,"Remyelination of demyelinated central nervous system (CNS) axons is considered as a potential treatment for multiple sclerosis, and it has been achieved in experimental models of demyelination by transplantation of pro-myelinating cells. However, the experiments undertaken have not addressed the need for tissue-type matching in order to achieve graft-mediated remyelination since they were performed in conditions in which the chance for graft rejection was minimized. This article focuses on the factors determining survival of allogeneic oligodendrocyte lineage cells and their contribution to the remyelination of demyelinating CNS lesions. The immune status of the CNS as well as the suitability of different models of demyelination for graft rejection studies are discussed, and ways of enhancing allogeneic oligodendrocyte-mediated remyelination are presented. Finally, the effects of glial graft rejection on host remyelination are described, highlighting the potential benefits of the acute CNS inflammatory response for myelin repair.",,"['Tepavčević, V', 'Blakemore, W.F']",,,,
,PMC,Unifying the spatial population dynamics and molecular evolution of epidemic rabies virus,http://dx.doi.org/10.1073/pnas.0500057102,PMC1186024,,,"Infectious disease emergence is under the simultaneous influence of both genetic and ecological factors. Yet, we lack a general framework for linking ecological dynamics of infectious disease with underlying molecular and evolutionary change. As a model, we illustrate the linkage between ecological and evolutionary dynamics in rabies virus during its epidemic expansion into eastern and southern Ontario. We characterized the phylogeographic relationships among 83 isolates of fox rabies virus variant using nucleotide sequences from the glycoprotein-encoding glycoprotein gene. The fox rabies virus variant descended as an irregular wave with two arms invading from northern Ontario into southern Ontario over the 1980s and 1990s. Correlations between genetic and geographic distance suggest an isolation by distance population structure for the virus. The divergence among viral lineages since the most recent common ancestor correlates with position along the advancing wave front with more divergent lineages near the origin of the epidemic. Based on divergence from the most recent common ancestor, the regional population can be partitioned into two subpopulations, each corresponding to an arm of the advancing wave. Subpopulation A (southern Ontario) showed reduced isolation by distance relative to subpopulation B (eastern Ontario). The temporal dynamics of subpopulation A suggests that the subregional viral population may have undergone several smaller waves that reduced isolation by distance. The use of integrated approaches, such as the geographical analysis of sequence variants, coupled with information on spatial dynamics will become indispensable aids in understanding patterns of disease emergence.",,"['Real, Leslie A.', 'Henderson, J. Caroline', 'Biek, Roman', 'Snaman, Jennifer', 'Jack, Tracy Lambert', 'Childs, James E.', 'Stahl, Eli', 'Waller, Lance', 'Tinline, Rowland', 'Nadin-Davis, Susan']",,,,
,PMC,Prevalence of porcine endogenous retrovirus in Chinese pig breeds and in patients treated with a porcine liver cell-based bioreactor,http://dx.doi.org/10.3748/wjg.v11.i30.4727,PMC4615419,,,"AIM: To determine the prevalence of porcine endogenous retrovirus (PERV) in various pig breeds raised in China including Chinese experimental mini-pigs by PERV-reverse transcriptase (PERV-RT enzyme). Moreover, the potential for infection of PERV was investigated in patients treated with a bioreactor based on porcine liver cells (n = 3). METHODS: Pig serum, liver and muscle cell-free supernatants were collected from various Chinese pig breeds. Porcine hepatocytes were isolated with a two-step perfusion method. Three patients with acute or chronic liver failure were treated with a bioartificial liver support system (BALSS) for 8-12 h and serum samples were collected from the patients before, immediately after and 30 d after treatment. RESULTS: The activities of PERV-RT enzyme in pig liver and muscle cell-free supernatants were higher than in normal human controls. PERV-TR enzyme activity did not increase in patients before and after 1 mo of treatment. PERV-RT activities were not significantly different when compared with pre-treatment group (1.544 ± 0.155576), the post-treatment groups (1.501 ± 0.053507, 1.461 ± 0.033808 and 1.6006667 ± 0.01963 for 0, 14 and 30 d post-treatment, respectively, P > 0.05), and normal control group (1.440 ± 1.0641, P > 0.05). RT enzyme activity in Chinese experimental mini-pigs was higher than in normal human control group (1.440 ± 1.0641 U/mL, P < 0.05), and not significantly different (P > 0.05) when compared with the pig breeds except in the muscle supernatants. All the samples including muscle and liver cell supernatants from the Chinese mini-experimental pigs and the four domestic Chinese pig breeds contained PERVs. CONCLUSION: These results suggest that the risk of PERV infection through BALSS containing porcine liver cells without immunosuppressants may be quite low. Although there were PERVs in Chinese experimental mini-pigs and porcine liver cell culture suspensions, we did not find any evidence of persistent PERV infection in patients treated with this porcine hepatocyte-based bioartificial liver.",,"['Liu, Qing', 'Liu, Zheng', 'Dalakas, Evangelos']",,,,
,PMC,The effect of disease life history on the evolutionary emergence of novel pathogens,http://dx.doi.org/10.1098/rspb.2005.3170,PMC1559879,,,"We present a general analytical result for the probability that a newly introduced pathogen will evolve adaptations that allow it to maintain itself within any novel host population, as a function of disease life-history parameters. We demonstrate that this probability of ‘evolutionary emergence’ depends on two key properties of the disease life history: (i) the basic reproduction number and (ii) the expected duration of an infection. These parameters encapsulate all of the relevant information and can be combined in a very simple expression, with estimates for the rates of adaptive mutation, to predict the probability of emergence for any novel pathogen. In general, diseases that initially have a large reproductive number and/or that cause relatively long infections are the most prone to evolutionary adaptation.",,"['André, Jean-Baptiste', 'Day, Troy']",,,,
,PMC,Helper-dependent adenoviral vectors in experimental gene therapy,,PMC1383728,,,"In the majority of potential applications gene therapy will require an effective transfer of a transgene in vivo resulting in high-level and long-term transgene expression, all in the absence of significant toxicity or inflammatory responses. The most efficient vehicles for delivery of foreign genes to the target tissues are modified adenoviruses. Adenoviral vectors of the first generation, despite the high infection efficacy, have an essential drawback: they induce strong immune response, which leads to short term expression of the transgene, and limits their usefulness in clinical trials. In contrast, helper-dependent adenoviral vectors (HdAd) lacking all viral coding sequences display only minimal immunogenicity and negligible side-effects, allowing for long-term transgene expression. Thus, HdAd vehicles have become the carrier of choice for adenoviral vector-mediated experimental gene therapy, effectively used in animal models for delivery of transgenes into the liver, skeletal muscle, myocardium or brain. Strong and long-lasting expression of therapeutic genes has allowed for successful treatment of dyslipidemias, muscular dystrophy, obesity, hemophilia, and diabetes. Additionally, the large cloning capacity of HdAd, up to 37 kb, facilitates the use of physiologically regulated, endogenous promoters, instead of artificial viral promoter sequences. This enables also generation of the single vectors expressing multiple genes, which can be potentially useful for treatment of polygenic diseases. In this review we characterize the basic features of HdAd vectors and describe some of their experimental and potential clinical applications.",,"['Józkowicz, Alicja', 'Dulak, Józef']",,,,
,PMC,Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry,http://dx.doi.org/10.1073/pnas.0505577102,PMC1188015,,,"Severe acute respiratory syndrome (SARS) is caused by an emergent coronavirus (SARS-CoV), for which there is currently no effective treatment. SARS-CoV mediates receptor binding and entry by its spike (S) glycoprotein, and infection is sensitive to lysosomotropic agents that perturb endosomal pH. We demonstrate here that the lysosomotropic-agent-mediated block to SARS-CoV infection is overcome by protease treatment of target-cell-associated virus. In addition, SARS-CoV infection was blocked by specific inhibitors of the pH-sensitive endosomal protease cathepsin L. A cell-free membrane-fusion system demonstrates that engagement of receptor followed by proteolysis is required for SARS-CoV membrane fusion and indicates that cathepsin L is sufficient to activate membrane fusion by SARS-CoV S. These results suggest that SARS-CoV infection results from a unique, three-step process: receptor binding and induced conformational changes in S glycoprotein followed by cathepsin L proteolysis within endosomes. The requirement for cathepsin L proteolysis identifies a previously uncharacterized class of inhibitor for SARS-CoV infection.",,"['Simmons, Graham', 'Gosalia, Dhaval N.', 'Rennekamp, Andrew J.', 'Reeves, Jacqueline D.', 'Diamond, Scott L.', 'Bates, Paul']",,,,
,PMC,Pneumonitis and Multi-Organ System Disease in Common Marmosets (Callithrix jacchus) Infected with the Severe Acute Respiratory Syndrome-Associated Coronavirus,,PMC1603565,,,"Severe acute respiratory syndrome (SARS) is a significant emerging infectious disease. Humans infected with the etiological agent, SARS-associated coronavirus (SARS-CoV), primarily present with pneumonitis but may also develop hepatic, gastrointestinal, and renal pathology. We inoculated common marmosets (Callithrix jacchus) with the objective of developing a small nonhuman primate model of SARS. Two groups of C. jacchus were inoculated intratracheally with cell culture supernatant containing SARS-CoV. In a time course pathogenesis study, animals were evaluated at 2, 4, and 7 days after infection for morphological changes and evidence of viral replication. All animals developed a multifocal mononuclear cell interstitial pneumonitis, accompanied by multinucleated syncytial cells, edema, and bronchiolitis in most animals. Viral antigen localized primarily to infected alveolar macrophages and type-1 pneumocytes by immunohistochemistry. Viral RNA was detected in all animals from pulmonary tissue extracts obtained at necropsy. Viral RNA was also detected in tracheobronchial lymph node and myocardium, together with inflammatory changes, in some animals. Hepatic inflammation was observed in most animals, predominantly as a multifocal lymphocytic hepatitis accompanied by necrosis of individual hepatocytes. These findings identify the common marmoset as a promising nonhuman primate to study SARS-CoV pathogenesis.",,"['Greenough, Thomas C.', 'Carville, Angela', 'Coderre, James', 'Somasundaran, Mohan', 'Sullivan, John L.', 'Luzuriaga, Katherine', 'Mansfield, Keith']",,,,
,PMC,How has research in the last five years changed my clinical practice?,http://dx.doi.org/10.1136/adc.2004.066241,PMC1720534,,,,,"Bush, A",,,,
,PMC,Jejunal hemorrhage syndrome in dairy and beef cattle: 11 cases (2001 to 2003),,PMC1180421,,,"The medical records of 11 cattle with jejunal hemorrhage syndrome were reviewed. Female and male, lactating and pregnant, dairy and beef cattle were affected. Decreased feed intake and milk production, reduced amounts of dark feces, and abdominal discomfort were common historical findings. Common clinical findings included depressed demeanor, a “ping” and fluid-splashing sounds over the right abdomen, melena, and distended loops of intestine on rectal palpation. Surgery was done on 7 cases, 10 cases were euthanized, and 1 died. Clostridium perfringens type A was isolated from the intestinal contents from 7 of 7 cases. At necropsy, the characteristic finding was a varying length of a dark purple-red distended jejunum with an intraluminal blood clot. Histologically, there was segmental necrosis, ulceration, and mucosal and transmural hemorrhage of the jejunum. This is a sporadic disease of adult cattle characterized by mechanical obstruction of the small intestines by a large blood clot with a case fatality of almost 100%.",,"['Abutarbush, Sameeh M.', 'Radostits, Otto M.']",,,,
,PMC,Preparing the Biochemistry Laboratory for the Next Outbreak: Lessons from SARS in Singapore,,PMC1240032,,,"Severe acute respiratory syndrome (SARS) is an emerging disease characterised by fever and atypical pneumonia and caused by a novel coronavirus. Singapore was affected by the global pandemic in early 2003, with 238 cases and 33 deaths. Samples sent to the biochemistry laboratory made up the majority (69%) of all SARS samples, yet remained a minority (29%) of total biochemistry workload. This paper describes the problems encountered and solutions adopted by the biochemistry laboratory at the designated SARS hospital in coping with this epidemic. It provides practical advice for laboratories planning for the handling of samples from future outbreaks.",,"Hawkins, Robert",,,,
,PMC,Altering the Tropism of Lentiviral Vectors through Pseudotyping,,PMC1368960,,,"The host range of retroviral vectors including lentiviral vectors can be expanded or altered by a process known as pseudotyping. Pseudotyped lentiviral vectors consist of vector particles bearing glycoproteins (GPs) derived from other enveloped viruses. Such particles possess the tropism of the virus from which the GP was derived. For example, to exploit the natural neural tropism of rabies virus, vectors designed to target the central nervous system have been pseudotyped using rabies virus-derived GPs. Among the first and still most widely used GPs for pseudotyping lentiviral vectors is the vesicular stomatitis virus GP (VSV-G), due to the very broad tropism and stability of the resulting pseudotypes. Pseudotypes involving VSV-G have become effectively the standard for evaluating the efficiency of other pseudotypes. This review samples a few of the more prominent examples from the ever-expanding list of published lentiviral pseudotypes, noting comparisons made with pseudotypes involving VSV-G in terms of titer, viral particle stability, toxicity, and host-cell specificity. Particular attention is paid to publications of successfully targeting a specific organ or cell types.",,"['Cronin, James', 'Zhang, Xian-Yang', 'Reiser, Jakob']",,,,
,PMC,Identification of Immunodominant Epitopes on the Membrane Protein of the Severe Acute Respiratory Syndrome-Associated Coronavirus,http://dx.doi.org/10.1128/JCM.43.8.3718-3726.2005,PMC1234014,,,"Similar to other coronaviruses, the membrane (M) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is a major transmembrane glycoprotein with multiple biological functions. To date, limited information is available about its antigenic properties. In this study, we identified two major immunodominant epitopes on the M protein located in the extreme N-terminal region (residues 1 to 31) and the interior C-terminal region (residues 132 to 161), respectively, by Pepscan analyses against convalescent-phase sera from SARS patients and antisera from virus-immunized mice and rabbits. Synthetic peptides M1-31 derived from the N-terminal epitope and M132-161 derived from the C-terminal epitope were highly reactive with all of the convalescent-phase sera from 40 SARS patients but not with 30 control serum samples from healthy blood donors, suggesting their potential application for serologic diagnosis of SARS. We showed that both peptides (M1-31 and M132-161) were able to induce high titers of antibody responses in the immunized rabbits, highlighting their antigenicity and immunogenicity. These findings provide important information for developing SARS diagnostics and vaccines.",,"['He, Yuxian', 'Zhou, Yusen', 'Siddiqui, Pamela', 'Niu, Jinkui', 'Jiang, Shibo']",,,,
,PMC,Performance of Single-Step Gel-Based Reverse Transcription-PCR (RT-PCR) Assays Equivalent to That of Real-Time RT-PCR Assays for Detection of the Severe Acute Respiratory Syndrome-Associated Coronavirus,http://dx.doi.org/10.1128/JCM.43.8.4262-4265.2005,PMC1233944,,,"Simple gel-based one-step reverse transcription-PCR (RT-PCR) assays, used to investigate patients during the 2003 severe acute respiratory syndrome (SARS) outbreak in Singapore, were found to be as sensitive as commercial and in-house real-time RT-PCR assays. The detection limit was approximately 1 genome equivalent (GE) per 5 μl PCR mixture. One PFU of SARS coronavirus was estimated to be 258 ± 46 GE.",,"['Inoue, Masafumi', 'Barkham, Timothy', 'Keong, Lee Kok', 'Gee, Lim Seng', 'Wanjin, Hong']",,,,
,PMC,Genomic RNA sequence of Feline coronavirus strain FIPV WSU-79/1146,http://dx.doi.org/10.1099/vir.0.80985-0,PMC2583351,,,"A consensus sequence of the Feline coronavirus (FCoV) (strain FIPV WSU-79/1146) genome was determined from overlapping cDNA fragments produced by RT-PCR amplification of viral RNA. The genome was found to be 29 125 nt in length, excluding the poly(A) tail. Analysis of the sequence identified conserved open reading frames and revealed an overall genome organization similar to that of other coronaviruses. The genomic RNA was analysed for putative cis-acting elements and the pattern of subgenomic mRNA synthesis was analysed by Northern blotting. Comparative sequence analysis of the predicted FCoV proteins identified 16 replicase proteins (nsp1–nsp16) and four structural proteins (spike, membrane, envelope and nucleocapsid). Two mRNAs encoding putative accessory proteins were also detected. Phylogenetic analyses confirmed that FIPV WSU-79/1146 belongs to the coronavirus subgroup G1-1. These results confirm and extend previous findings from partial sequence analysis of FCoV genomes.",,"['Dye, Charlotte', 'Siddell, Stuart G.']",,,,
,PMC,Novel Vaccination Strategies,,PMC2576006,,,,,"Leung, Alexander K. C.",,,,
,PMC,Caveola-Dependent Endocytic Entry of Amphotropic Murine Leukemia Virus,http://dx.doi.org/10.1128/JVI.79.16.10776-10787.2005,PMC1182675,,,"Early results suggested that the amphotropic murine leukemia virus (A-MLV) does not enter cells via endocytosis through clathrin-coated pits and this gammaretrovirus has therefore been anticipated to fuse directly with the plasma membrane. However, here we present data implicating a caveola-mediated endocytic entry route for A-MLV via its receptor Pit2. Caveolae belong to the cholesterol-rich microdomains characterized by resistance to nonionic detergents such as Triton X-100. Extraction of murine fibroblastic NIH 3T3 cells in cold Triton X-100 showed the presence of the A-MLV receptor Pit2 in detergent-insoluble microdomains. Using coimmunoprecipitation of cell extracts, we were able to demonstrate direct association of Pit2 with caveolin-1, the structural protein of caveolae. Other investigations revealed that A-MLV infection in contrast to vesicular stomatitis virus infection is a slow process (t ≈5 h), which is dependent on plasma membrane cholesterol but independent of NH(4)Cl treatment of cells; NH(4)Cl impairs entry via clathrin-coated pits. Furthermore, expression of dominant-negative caveolin-1 decreased the susceptibility to infection via Pit2 by approximately 70%. These results show that A-MLV can enter cells via a caveola-dependent entry route. Moreover, increase in A-MLV infection by treatment with okadaic acid as well as entry of fusion-defective fluorescent A-MLV virions in NIH 3T3 cells further confirmed our findings and show that A-MLV can enter mouse fibroblasts via an endocytic entry route involving caveolae. Finally, we also found colocalization of fusion-defective fluorescent A-MLV virions with caveolin-1 in NIH 3T3 cells. This is the first time substantial evidence has been presented implicating the existence of a caveola-dependent endocytic entry pathway for a retrovirus.",,"['Beer, Christiane', 'Andersen, Ditte S.', 'Rojek, Aleksandra', 'Pedersen, Lene']",,,,
,PMC,Important Roles for Gamma Interferon and NKG2D in γδ T-Cell-Induced Demyelination in T-Cell Receptor β-Deficient Mice Infected with a Coronavirus,http://dx.doi.org/10.1128/JVI.79.15.9388-9396.2005,PMC1181615,,,"γδ T cells mediate demyelination in athymic (nude) mice infected with the neurotropic coronavirus mouse hepatitis virus strain JHM. Now, we show that these cells also mediate the same process in mice lacking αβ T cells (T-cell receptor β-deficient [TCRβ(−/−)] mice) and demyelination is gamma interferon (IFN-γ) dependent. Most strikingly, our results also show a major role for NKG2D, expressed on γδ T cells, in the demyelinating process with in vivo blockade of NKG2D interactions resulting in a 60% reduction in demyelination. NKG2D may serve as a primary recognition receptor or as a costimulatory molecule. We show that NKG2D(+) γδ T cells in the JHM-infected central nervous system express the adaptor molecule DAP12 and an NKG2D isoform (NKG2D short), both required for NKG2D to serve as a primary receptor. These results are consistent with models in which γδ T cells mediate demyelination using the same effector cytokine, IFN-γ, as CD8 T cells and do so without a requirement for signaling through the TCR.",,"['Dandekar, Ajai A.', ""O'Malley, Katherine"", 'Perlman, Stanley']",,,,
,PMC,"Inhibition, Escape, and Attenuated Growth of Severe Acute Respiratory Syndrome Coronavirus Treated with Antisense Morpholino Oligomers",http://dx.doi.org/10.1128/JVI.79.15.9665-9676.2005,PMC1181598,,,"The recently emerged severe acute respiratory syndrome coronavirus (SARS-CoV) is a potent pathogen of humans and is capable of rapid global spread. Peptide-conjugated antisense morpholino oligomers (P-PMO) were designed to bind by base pairing to specific sequences in the SARS-CoV (Tor2 strain) genome. The P-PMO were tested for their capacity to inhibit production of infectious virus as well as to probe the function of conserved viral RNA motifs and secondary structures. Several virus-targeted P-PMO and a random-sequence control P-PMO showed low inhibitory activity against SARS coronavirus. Certain other virus-targeted P-PMO reduced virus-induced cytopathology and cell-to-cell spread as a consequence of decreasing viral amplification. Active P-PMO were effective when administered at any time prior to peak viral synthesis and exerted sustained antiviral effects while present in culture medium. P-PMO showed low nonspecific inhibitory activity against translation of nontargeted RNA or growth of the arenavirus lymphocytic choriomeningitis virus. Two P-PMO targeting the viral transcription-regulatory sequence (TRS) region in the 5′ untranslated region were the most effective inhibitors tested. After several viral passages in the presence of a TRS-targeted P-PMO, partially drug-resistant SARS-CoV mutants arose which contained three contiguous base point mutations at the binding site of a TRS-targeted P-PMO. Those partially resistant viruses grew more slowly and formed smaller plaques than wild-type SARS-CoV. These results suggest PMO compounds have powerful therapeutic and investigative potential toward coronavirus infection.",,"['Neuman, Benjamin W.', 'Stein, David A.', 'Kroeker, Andrew D.', 'Churchill, Michael J.', 'Kim, Alice M.', 'Kuhn, Peter', 'Dawson, Philip', 'Moulton, Hong M.', 'Bestwick, Richard K.', 'Iversen, Patrick L.', 'Buchmeier, Michael J.']",,,,
,PMC,Murine Coronavirus Requires Lipid Rafts for Virus Entry and Cell-Cell Fusion but Not for Virus Release,http://dx.doi.org/10.1128/JVI.79.15.9862-9871.2005,PMC1181594,,,"Thorp and Gallagher first reported that depletion of cholesterol inhibited virus entry and cell-cell fusion of mouse hepatitis virus (MHV), suggesting the importance of lipid rafts in MHV replication (E. B. Thorp and T. M. Gallagher, J. Virol. 78:2682-2692, 2004). However, the MHV receptor is not present in lipid rafts, and anchoring of the MHV receptor to lipid rafts did not enhance MHV infection; thus, the mechanism of lipid rafts involvement is not clear. In this study, we defined the mechanism and extent of lipid raft involvement in MHV replication. We showed that cholesterol depletion by methyl β-cyclodextrin or filipin did not affect virus binding but reduced virus entry. Furthermore, MHV spike protein bound to nonraftraft membrane at 4°C but shifted to lipid rafts at 37°C, indicating a redistribution of membrane following virus binding. Thus, the lipid raft involvement in MHV entry occurs at a step following virus binding. We also found that the viral spike protein in the plasma membrane of the infected cells was associated with lipid rafts, whereas that in the Golgi membrane, where MHV matures, was not. Moreover, the buoyant density of the virion was not changed when MHV was produced from the cholesterol-depleted cells, suggesting that MHV does not incorporate lipid rafts into the virion. These results indicate that MHV release does not involve lipid rafts. However, MHV spike protein has an inherent ability to associate with lipid rafts. Correspondingly, cell-cell fusion induced by MHV was retarded by cholesterol depletion, consistent with the association of the spike protein with lipid rafts in the plasma membrane. These findings suggest that MHV entry requires specific interactions between the spike protein and lipid rafts, probably during the virus internalization step.",,"['Choi, Keum S.', 'Aizaki, Hideki', 'Lai, Michael M. C.']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.79.15.9367-9368.2005,PMC1181590,,,,,,,,,
,PMC,The Severe Acute Respiratory Syndrome Coronavirus 3a Protein Up-Regulates Expression of Fibrinogen in Lung Epithelial Cells,http://dx.doi.org/10.1128/JVI.79.15.10083-10087.2005,PMC1181587,,,"Here we analyzed the gene expression profile of cells that stably express the severe acute respiratory syndrome coronavirus (SARS-CoV) 3a protein to determine its effects on host functions. A lung epithelial cell-line, A549, was chosen for this study because the lung is the primary organ infected by SARS-CoV and fatalities resulted mainly from pulmonary complications. Our results showed that the expression of 3a up-regulates the mRNA levels of all three subunits, Aα, Bβ, and γ, of fibrinogen. Consequently, the intracellular levels as well as the secretion of fibrinogen were increased. We also observed increased fibrinogen levels in SARS-CoV-infected Vero E6 cells.",,"['Tan, Yee-Joo', 'Tham, Puay-Yoke', 'Chan, Daphne Z. L.', 'Chou, Chih-Fong', 'Shen, Shuo', 'Fielding, Burtram C.', 'Tan, Timothy H. P.', 'Lim, Seng Gee', 'Hong, Wanjin']",,,,
,PMC,Mechanism of Stimulation of Plus-Strand Synthesis by an RNA Replication Enhancer in a Tombusvirus,http://dx.doi.org/10.1128/JVI.79.15.9777-9785.2005,PMC1181556,,,"Replication of RNA viruses is regulated by cis-acting RNA elements, including promoters, replication silencers, and replication enhancers (REN). To dissect the function of an REN element involved in plus-strand RNA synthesis, we developed an in vitro trans-replication assay for tombusviruses, which are small plus-strand RNA viruses. In this assay, two RNA strands were tethered together via short complementary regions with the REN present in the nontemplate RNA, whereas the promoter was located in the template RNA. We found that the template activity of the tombusvirus replicase preparation was stimulated in trans by the REN, suggesting that the REN is a functional enhancer when located in the vicinity of the promoter. In addition, this study revealed that the REN has dual function during RNA synthesis. (i) It binds to the viral replicase. (ii) It interacts with the core plus-strand initiation promoter via a long-distance RNA-RNA interaction, which leads to stimulation of initiation of plus-strand RNA synthesis by the replicase in vitro. We also observed that this RNA-RNA interaction increased the in vivo accumulation and competitiveness of defective interfering RNA, a model template. We propose that REN is important for asymmetrical viral RNA replication that leads to more abundant plus-strand RNA progeny than the minus-strand intermediate, a hallmark of replication of plus-strand RNA viruses.",,"['Panavas, Tadas', 'Nagy, Peter D.']",,,,
,PMC,Apical Entry and Release of Severe Acute Respiratory Syndrome-Associated Coronavirus in Polarized Calu-3 Lung Epithelial Cells,http://dx.doi.org/10.1128/JVI.79.15.9470-9479.2005,PMC1181546,,,"Severe acute respiratory syndrome (SARS), caused by a novel coronavirus (CoV) known as SARS-CoV, is a contagious and life-threatening respiratory illness with pneumocytes as its main target. A full understanding of how SARS-CoV would interact with lung epithelial cells will be vital for advancing our knowledge of SARS pathogenesis. However, an in vitro model of SARS-CoV infection using relevant lung epithelial cells is not yet available, making it difficult to dissect the pathogenesis of SARS-CoV in the lungs. Here, we report that SARS-CoV can productively infect human bronchial epithelial Calu-3 cells, causing cytopathic effects, a process reflective of its natural course of infection in the lungs. Indirect immunofluorescence studies revealed a preferential expression of angiotensin-converting enzyme 2 (ACE-2), the functional receptor of SARS-CoV, on the apical surface. Importantly, both ACE-2 and viral antigen appeared to preferentially colocalize at the apical domain of infected cells. In highly polarized Calu-3 cells grown on the membrane inserts, we found that cells exposed to virus through the apical rather than the basolateral surface showed high levels of viral replication. Progeny virus was released into the apical chamber at titers up to 5 logs higher than those recovered from the basolateral chambers of polarized cultures. Taken together, these results indicate that SARS-CoV almost exclusively entered and was released from the apical domain of polarized Calu-3 cells, which might provide important insight into the mechanism of transmission and pathogenesis of SARS-CoV.",,"['Tseng, Chien-Te K.', 'Tseng, Jennifer', 'Perrone, Lucy', 'Worthy, Melissa', 'Popov, Vsevolod', 'Peters, Clarence J.']",,,,
,PMC,Aristotle's answer (2): Decision making in general practice: the practice of perception,,PMC2560890,,,,,,,,,
,PMC,Plant Virus RNAs. Coordinated Recruitment of Conserved Host Functions by (+) ssRNA Viruses during Early Infection Events,http://dx.doi.org/10.1104/pp.105.064105,PMC1183374,,,"Positive-sense single-stranded RNA viruses have developed strategies to exploit cellular resources at the expense of host mRNAs. The genomes of these viruses display a variety of structures at their 5′ and 3′ ends that differentiate them from cellular mRNAs. Despite this structural diversity, viral RNAs are still circularized by juxtaposition of their 5′ and 3′ ends, similar to the process used by cellular mRNAs. Also reminiscent of the mechanisms used by host mRNAs, translation of viral RNAs involves the recruitment of translation initiation factors. However, the roles played by these factors likely differ from those played by cellular mRNAs. In keeping with the general parsimony typical of RNA viruses, these host factors also participate in viral RNA replication. However, the dual use of host factors requires that viral RNA template utilization be regulated to avoid conflict between replication and translation. The molecular composition of the large ribonucleoprotein complexes that form the viral RNA replication and translation machineries likely evolves over the course of infection to allow for switching template use from translation to replication.",,"['Thivierge, Karine', 'Nicaise, Valérie', 'Dufresne, Philippe J.', 'Cotton, Sophie', 'Laliberté, Jean-François', 'Le Gall, Olivier', 'Fortin, Marc G.']",,,,
,PMC,T Cell Memory in the Lung Airways,http://dx.doi.org/10.1513/pats.200501-003AW,PMC2713315,,,"The respiratory tract poses a substantial challenge to the immune system due to its large surface area, an extensive vasculature that is in very close proximity to the external environment, and repeated exposure to potentially pathogenic organisms in the air. Yet many lung pathogens are controlled by appropriate immune responses. The underlying mechanisms of the adaptive cellular immune response in protecting the respiratory tract are poorly understood. Recently, it has emerged that memory CD4(+) and CD8(+) T cells are present in the lung airways, and evidence is mounting that these cells play a key role in pulmonary immunity to pathogen challenge by immediately engaging the pathogen at the site of infection when pathogen loads are low. For example, in the case of respiratory virus infections, there is evidence that both CD4(+) and CD8(+) memory cells in the lung airways mediate substantial control of a secondary respiratory virus infection in the lungs. Here we address recent developments in our understanding of lung airway memory T cells and their role in infectious disease.",,"['Woodland, David L.', 'Scott, Iain']",,,,
,PMC,Ribavirin is not a functional mimic of the 7-methyl guanosine mRNA cap,http://dx.doi.org/10.1261/rna.2930805,PMC1370807,,,"Ribavirin is a guanosine ribonucleoside analog that displays broad-spectrum anti-viral activity and is currently used for the treatment of some viral infections. Ribavirin has recently been proposed to also be a mimic of the 7-methyl guanosine cap found at the 5′ end of mRNAs. To obtain supporting functional data for this hypothesis, we assessed the ability of ribavirin triphosphate to interfere with the interaction between eIF4E and 7-methyl guanosine capped mRNA. In chemical cross-linking assays, cap-affinity chromatography, and cap-dependent translation assays, ribavirin was unable to function as a cap analog.",,"['YAN, YIFEI', 'SVITKIN, YURI', 'LEE, JOSEPH M.', 'BISAILLON, MARTIN', 'PELLETIER, JERRY']",,,,
,PMC,"""Not safe"" is not enough: smokers have a right to know more than there is no safe tobacco product",http://dx.doi.org/10.1136/tc.2004.008334,PMC1766193,,,"The right to health relevant information derives from the principles of autonomy and self direction and has been recognised in international declarations. Providing accurate health information is part of the basis for obtaining ""informed consent"" and is a recognised component of business ethics, safety communications, and case and product liability law. Remarkably, anti-tobacco and pro-tobacco sources alike have come to emphasise the message that there is ""no safe cigarette"" or ""no safe tobacco product"". We propose that the ""no safe"" message is so limited in its value that it represents a violation of the right to health relevant information. There is a need to go beyond saying, ""there is no safe tobacco product"" to indicate information on degree of risks. The ""no safe tobacco"" message does not contradict, for example, the mistaken belief that so called light or low tar cigarettes are safer choices than higher tar cigarettes. We encourage a kind of ""rule utilitarian"" ethical position in which the principle of truth telling is observed while trying to produce the greatest good for the greatest number of people. Although harm reduction approaches to easing the burden of tobacco related diseases are founded on science based comparative risk information, the right to health information is independently related to the need to promote health literacy. This right should be respected whether or not harm reduction policies are judged advisable.",,"['Kozlowski, L', 'Edwards, B']",,,,
,PMC,Ethical and legal aspects of global tobacco control,http://dx.doi.org/10.1136/tc.2004.008284,PMC1766191,,,"On 28 February 2005, the Framework Convention on Tobacco Control came into force as a result of at least 40 countries becoming State Parties through ratification of this first ever health treaty sponsored by the World Health Organization. This article discusses the bioethical, trade, and legal aspects of global tobacco control. Special emphasis is given to globalisation of tobacco use and the challenges it poses to sovereign nations. It also advocates a bioethical basis in the pursuit of global solutions to expanding tobacco use.",,"['Novotny, T', 'Carlin, D']",,,,
,PMC,WHO increases pressure on China over bird flu,,PMC1181260,,,,,"Zarocostas, John",,,,
,PMC,In brief,,PMC1181258,,,,,,,,,
,PMC,"Multiscale, resurgent epidemics in a hierarchical metapopulation model",http://dx.doi.org/10.1073/pnas.0501226102,PMC1183543,,,"Although population structure has long been recognized as relevant to the spread of infectious disease, traditional mathematical models have understated the role of nonhomogenous mixing in populations with geographical and social structure. Recently, a wide variety of spatial and network models have been proposed that incorporate various aspects of interaction structure among individuals. However, these more complex models necessarily suffer from limited tractability, rendering general conclusions difficult to draw. In seeking a compromise between parsimony and realism, we introduce a class of metapopulation models in which we assume homogeneous mixing holds within local contexts, and that these contexts are embedded in a nested hierarchy of successively larger domains. We model the movement of individuals between contexts via simple transport parameters and allow diseases to spread stochastically. Our model exhibits some important stylized features of real epidemics, including extreme size variation and temporal heterogeneity, that are difficult to characterize with traditional measures. In particular, our results suggest that when epidemics do occur the basic reproduction number R(0) may bear little relation to their final size. Informed by our model's behavior, we suggest measures for characterizing epidemic thresholds and discuss implications for the control of epidemics.",,"['Watts, Duncan J.', 'Muhamad, Roby', 'Medina, Daniel C.', 'Dodds, Peter S.']",,,,
,PMC,Excretion and detection of SARS coronavirus and its nucleic acid from digestive system,http://dx.doi.org/10.3748/wjg.v11.i28.4390,PMC4434667,,,"AIM: To study whether severe acute respiratory syndrome coronavirus (SARS-CoV) could be excreted from digestive system. METHODS: Cell culture and semi-nested RT-PCR were used to detect SARS-CoV and its RNA from 21 stool and urine samples, and a kind of electropositive filter media particles was used to concentrate the virus in 10 sewage samples from two hospitals receiving SARS patients in Beijing in China. RESULTS: It was demonstrated that there was no live SARS-CoV in all samples collected, but the RNA of SARS-CoV could be detected in seven stool samples from SARS patients with any one of the symptoms of fever, malaise, cough, or dyspnea, in 10 sewage samples before disinfection and 3 samples after disinfection from the two hospitals. The RNA could not be detected in urine and stool samples from patients recovered from SARS. CONCLUSION: Nucleic acid of SARS-CoV can be excreted through the stool of patients into sewage system, and the possibility of SARS-CoV transmitting through digestive system cannot be excluded.",,"['Wang, Xin-Wei', 'Li, Jin-Song', 'Guo, Ting-Kai', 'Zhen, Bei', 'Kong, Qing-Xin', 'Yi, Bin', 'Li, Zhong', 'Song, Nong', 'Jin, Min', 'Wu, Xiao-Ming', 'Xiao, Wen-Jun', 'Zhu, Xiu-Mei', 'Gu, Chang-Qing', 'Yin, Jing', 'Wei, Wei', 'Yao, Wei', 'Liu, Chao', 'Li, Jian-Feng', 'Ou, Guo-Rong', 'Wang, Min-Nian', 'Fang, Tong-Yu', 'Wang, Gui-Jie', 'Qiu, Yao-Hui', 'Wu, Huai-Huan', 'Chao, Fu-Huan', 'Li, Jun-Wen']",,,,
,PMC,Seroprevalence of IgG antibodies to SARS-coronavirus in asymptomatic or subclinical population groups,http://dx.doi.org/10.1017/S0950268805004826,PMC2870380,,,"We systematically reviewed the current understanding of human population immunity against SARS-CoV in different groups, settings and geography. Our meta-analysis, which included all identified studies except those on wild animal handlers, yielded an overall seroprevalence of 0·10% [95% confidence interval (CI) 0·02–0·18]. Health-care workers and others who had close contact with SARS patients had a slightly higher degree of seroconversion (0·23%, 95% CI 0·02–0·45) compared to healthy blood donors, others from the general community or non-SARS patients recruited from the health-care setting (0·16%, 95% CI 0–0·37). When analysed by the two broad classes of testing procedures, it is clear that serial confirmatory test protocols resulted in a much lower estimate (0·050%, 95% CI 0–0·15) than single test protocols (0·20%, 95% CI 0·06–0·34). Potential epidemiological and laboratory pitfalls are also discussed as they may give rise to false or inconsistent results in measuring the seroprevalence of IgG antibodies to SARS-CoV.",,"['LEUNG, G.\xa0M.', 'LIM, W.\xa0W.', 'HO, L.-M.', 'LAM, T.-H.', 'GHANI, A.\xa0C.', 'DONNELLY, C.\xa0A.', 'FRASER, C.', 'RILEY, S.', 'FERGUSON, N.\xa0M.', 'ANDERSON, R.\xa0M.', 'HEDLEY, A.\xa0J.']",,,,
,PMC,Genome-wide screen identifies host genes affecting viral RNA recombination,http://dx.doi.org/10.1073/pnas.0504844102,PMC1180806,,,"Rapid evolution of RNA viruses with mRNA-sense genomes is a major concern to health and economic welfare because of the devastating diseases these viruses inflict on humans, animals, and plants. To test whether host genes can affect the evolution of RNA viruses, we used a Saccharomyces cerevisiae single-gene deletion library, which includes ≈80% of yeast genes, in RNA recombination studies based on a small viral replicon RNA derived from tomato bushy stunt virus. The genome-wide screen led to the identification of five host genes whose absence resulted in the rapid generation of new viral RNA recombinants. Thus, these genes normally suppress viral RNA recombination, but in their absence, hosts become viral recombination “hotbeds.” Four of the five suppressor genes are likely involved in RNA degradation, suggesting that RNA degradation could play a role in viral RNA recombination. In contrast, deletion of four other host genes inhibited virus recombination, indicating that these genes normally accelerate the RNA recombination process. A comparison of deletion strains with the lowest and the highest recombination rate revealed that host genes could affect recombinant accumulation by up to 80-fold. Overall, our results demonstrate that a set of host genes have a major effect on RNA virus recombination and evolution.",,"['Serviene, Elena', 'Shapka, Natalia', 'Cheng, Chi-Ping', 'Panavas, Tadas', 'Phuangrat, Bencharong', 'Baker, Jannine', 'Nagy, Peter D.']",,,,
,PMC,Novel rapid immunochromatographic test based on an enzyme immunoassay for detecting nucleocapsid antigen in SARS‐associated coronavirus,http://dx.doi.org/10.1002/jcla.20070,PMC6807888,,,"A novel severe acute respiratory syndrome‐associated coronavirus (SARS‐CoV) has been discovered. The detection of both antigens and antibodies in SARS‐CoV from human specimens with suspected SARS plays an important role in preventing infection. We developed a novel rapid immunochromatographic test (RICT) based on the sandwich format enzyme immunoassay (EIA) with an all‐in‐one device for detecting the native nucleocapsid antigen (N‐Ag) of SARS‐CoV using monoclonal antibodies (MoAbs), which we produced by immunizing recombinant N‐Ag to mice. RICT is a qualitative assay for respiratory aspirates and serum specimens. With this assay, a positive result can be judged subjectively by the appearance of a blue line on the device 15 min after the sample is applied. RICT with several pairs of MoAbs showed a high sensitivity for the detection of recombinant N‐Ag as well as viral N‐Ag of SARS‐CoV. rSN122 and rSN21‐2 were the best MoAbs for immobilized antibody and enzyme labeling, respectively. With regard to analytical sensitivity, RICT detected N‐Ag at 31 pg/mL for recombinant N‐Ag, and at 1.99×10(2) TCID(50)/mL for SARS‐CoV. The specificity of RICT was 100% when 150 human sera and 50 nasopharyngeal aspirates (NSPs) were used. RICT based on an EIA using the rSN122/rSN21‐2 pair is a sensitive, specific, and reliable rapid assay for detecting N‐Ag in SARS‐CoV treated with either heat or Triton X‐100. J. Clin. Lab. Anal. 19:150–159, 2005. © 2005 Wiley‐Liss, Inc.",,"['Kogaki, Hiroyuki', 'Uchida, Yoshiaki', 'Fujii, Nobuyuki', 'Kurano, Yoshihiro', 'Miyake, Kazushige', 'Kido, Yasuji', 'Kariwa, Hiroaki', 'Takashima, Ikuo', 'Tamashiro, Hiko', 'Ling, Ai‐Ee', 'Okada, Masahisa']",,,,
,PMC,In brief,,PMC558518,,,,,,,,,
,PMC,In the Name of Public Health,http://dx.doi.org/10.2105/AJPH.2004.058065,PMC1449322,,,,,"['Birn, Anne-Emanuelle', 'Molina, Natalia']",,,,
,PMC,Schools and adolescent health,,PMC1720477,,,,,,,,,
,PMC,A case-control study of SARS versus community acquired pneumonia,http://dx.doi.org/10.1136/adc.2004.063446,PMC1720467,,,,,"['Cheng, F', 'Ng, P', 'Chiu, W', 'Chu, W', 'Li, A', 'Lo, K', 'Hon, E', 'Nelson, E', 'Leung, T', 'Ng, W', 'Wong, E', 'Ip, P', 'Fok, T']",,,,
,PMC,Improving the evidence base for pre-travel advice: the importance of surveillance of travel-associated infection,,PMC1472775,,,,,"['Lawrence, Joanne', 'Jones, Jane', 'Hill, David R']",,,,
,PMC,Evaluation of Inapparent Nosocomial Severe Acute Respiratory Syndrome Coronavirus Infection in Vietnam by Use of Highly Specific Recombinant Truncated Nucleocapsid Protein-Based Enzyme-Linked Immunosorbent Assay,http://dx.doi.org/10.1128/CDLI.12.7.848-854.2005,PMC1182204,,,"Severe acute respiratory syndrome (SARS) is a recently emerged human disease associated with pneumonia. Inapparent infection with SARS coronavirus (CoV) is not well characterized. To develop a safe, simple, and reliable screening method for SARS diagnosis and epidemiological study, two recombinant SARS-CoV nucleocapsid proteins (N′ protein and NΔ(121) protein) were expressed in Escherichia coli, purified by affinity chromatography, and used as antigens for indirect, immunoglobulin G enzyme-linked immunosorbent assays (ELISA). Serum samples collected from healthy volunteers and SARS patients in Vietnam were used to evaluate the newly developed methods. The N′ protein-based ELISA showed a highly nonspecific reaction. The NΔ(121) protein-based ELISA, with a nonspecific reaction drastically reduced compared to that of the nearly-whole-length N′ protein-based ELISA, resulted in higher rates of positive reactions, higher titers, and earlier detection than the SARS-CoV-infected cell lysate-based ELISA. These results indicate that our newly developed SARS-CoV NΔ(121) protein-based ELISA is not only safe but also a more specific and more sensitive method to diagnose SARS-CoV infection and hence a useful tool for large-scale epidemiological studies. To identify inapparent SARS-CoV infections, serum samples collected from health care workers (HCWs) in Vietnam were screened by the NΔ(121) protein-based ELISA, and positive samples were confirmed by a virus neutralization test. Four out of 149 HCWs were identified to have inapparent SARS-CoV infection in Vietnam, indicating that subclinical SARS-CoV infection in Vietnam is rare but does exist.",,"['Yu, Fuxun', 'Le, Mai Quynh', 'Inoue, Shingo', 'Thai, Hong Thi Cam', 'Hasebe, Futoshi', 'del Carmen Parquet, Maria', 'Morita, Kouichi']",,,,
,PMC,Epidemiology and Management of Infectious Diseases in International Adoptees,http://dx.doi.org/10.1128/CMR.18.3.510-520.2005,PMC1195971,,,"International adoptees represent a group of children with unique health care needs. Data from published studies, along with the recent experience of the Yale International Adoption Clinic, suggest that the risk of serious infections in adoptees is low, although infections associated with institutionalization still occur commonly. Interpretation of these data must be undertaken with caution, however, since many, if not most, international adoptees are not evaluated in specialty clinics. Thus, prospective studies designed to minimize selection and referral bias are needed in order to accurately define the risk of infectious and noninfectious diseases in all international adoptees.",,"['Murray, Thomas S.', 'Groth, M. Elizabeth', 'Weitzman, Carol', 'Cappello, Michael']",,,,
,PMC,Future trends and challenges in pathogenomics,http://dx.doi.org/10.1038/sj.embor.7400472,PMC1369123,,,A Foresight study,,"['Pompe, Sven', 'Simon, Judith', 'Wiedemann, Peter M.', 'Tannert, Christof']",,,,
,PMC,Differential Sensitivities of Severe Acute Respiratory Syndrome (SARS) Coronavirus Spike Polypeptide Enzyme-Linked Immunosorbent Assay (ELISA) and SARS Coronavirus Nucleocapsid Protein ELISA for Serodiagnosis of SARS Coronavirus Pneumonia,http://dx.doi.org/10.1128/JCM.43.7.3054-3058.2005,PMC1169156,,,"The use of recombinant severe acute respiratory syndrome-coronavirus (SARS-CoV) nucleocapsid protein (N) enzyme-linked immunosorbent assay (ELISA)-based antibody and antigen tests for diagnosis of SARS-CoV infections have been widely reported. However, no recombinant SARS-CoV spike protein (S)-based ELISA is currently available. In this article, we describe the problems and solutions of setting up the recombinant SARS-CoV S-based ELISA for antibody detection. The SARS-CoV S-based immunoglobulin M (IgM) and IgG ELISAs were evaluated and compared with the corresponding N-based ELISA for serodiagnosis of SARS-CoV pneumonia, using sera from 148 healthy blood donors who donated blood 3 years ago as controls and 95 SARS-CoV pneumonia patients in Hong Kong. Results obtained by the recombinant S (rS)-based IgG ELISA using the regenerated S prepared by dialysis with decreasing concentrations of urea or direct addition of different coating buffers, followed by addition of different regeneration buffer, identified 4 M urea and 1 M sarcosine for plate coating and no regeneration buffer as the most optimal conditions for antibody detection. The specificities of the S-based ELISA for IgG and IgM detection were 98.6% and 93.9%, with corresponding sensitivities of 58.9% and 74.7%, respectively. The sensitivity of the rN IgG ELISA (94.7%) is significantly higher than that of the rS IgG ELISA (P < 0.001), whereas the sensitivity of the rS IgM ELISA is significantly higher than that of the rN IgM ELISA (55.2%) (P < 0.01). An ELISA for detection of IgM against S and N could be more sensitive than one that detects IgM against N alone for serodiagnosis of SARS-CoV pneumonia.",,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Wong, Beatrice H. L.', 'Tsoi, Hoi-wah', 'Fung, Ami M. Y.', 'Kao, Richard Y. T.', 'Chan, Kwok-hung', 'Peiris, J. S. Malik', 'Yuen, Kwok-yung']",,,,
,PMC,Sensitive and Rapid Detection of Herpes Simplex Virus and Varicella-Zoster Virus DNA by Loop-Mediated Isothermal Amplification,http://dx.doi.org/10.1128/JCM.43.7.3290-3296.2005,PMC1169145,,,"Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification method in which reagents react rapidly and efficiently, with a high specificity, under isothermal conditions. We used a LAMP assay for the detection of herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and varicella-zoster virus (VZV). The virus specificities of primers were confirmed by using 50 HSV-1, 50 HSV-2, and 8 VZV strains. The assay was performed for 45 min at 65°C. The LAMP assay had a 10-fold higher sensitivity than a PCR assay. An analysis of nucleotide sequence variations in the target and primer regions used for the LAMP assay indicated that 3 of 50 HSV-1 strains had single nucleotide polymorphisms. No HSV-2 or VZV strains had nucleotide polymorphisms. Regardless of the sequence variation, there were no differences in sensitivity with the HSV-1-specific LAMP assay. To evaluate the application of the LAMP assay for clinical diagnosis, we tested clinical samples from 40 genital herpes patients and 20 ocular herpes patients. With the LAMP assay, 41 samples with DNA extraction and 26 direct samples without DNA extraction were identified as positive for HSV-1 or HSV-2, although 37 samples with DNA extraction and just one without DNA extraction were positive by a PCR assay. Thus, the LAMP assay was less influenced than the PCR assay by the presence of inhibitory substances in clinical samples. These observations indicate that the LAMP assay is very useful for the diagnosis of HSV-1, HSV-2, and VZV infections.",,"['Kaneko, Hisatoshi', 'Iida, Tomohiro', 'Aoki, Koki', 'Ohno, Shigeaki', 'Suzutani, Tatsuo']",,,,
,PMC,Characterization of a New Species of Adenovirus in Falcons,http://dx.doi.org/10.1128/JCM.43.7.3402-3413.2005,PMC1169131,,,"In 1996, a disease outbreak occurred at a captive breeding facility in Idaho, causing anorexia, dehydration, and diarrhea or sudden death in 72 of 110 Northern aplomado falcons (Falco femoralis septentrionalis) from 9 to 35 days of age and in 6 of 102 peregrine falcons (Falco peregrinus) from 14 to 25 days of age. Sixty-two Northern aplomado and six peregrine falcons died. Epidemiologic analyses indicated a point source epizootic, horizontal transmission, and increased relative risk associated with cross-species brooding of eggs. Primary lesions in affected birds were inclusion body hepatitis, splenomegaly, and enteritis. The etiology in all mortalities was determined by molecular analyses to be a new species of adenovirus distantly related to the group I avian viruses, serotypes 1 and 4, Aviadenovirus. In situ hybridization and PCR demonstrated that the virus was epitheliotropic and lymphotropic and that infection was systemic in the majority of animals. Adeno-associated virus was also detected by PCR in most affected falcons, but no other infectious agents or predisposing factors were found in any birds. Subsequent to the 1996 epizootic, a similar disease caused by the same adenovirus was found over a 5-year period in orange-breasted falcons (Falco deiroleucus), teita falcons (Falco fasciinucha), a merlin (Falco columbarius), a Vanuatu peregrine falcon (Falco peregrinus nesiotes), and gyrfalcon × peregrine falcon hybrids (Falco rusticolus/peregrinus) that died in Wyoming, Oklahoma, Minnesota, and California. These findings indicate that this newly recognized adenovirus is widespread in western and midwestern North America and can be a primary pathogen in different falcon species.",,"['Schrenzel, Mark', 'Oaks, J. Lindsay', 'Rotstein, Dave', 'Maalouf, Gabriel', 'Snook, Eric', 'Sandfort, Cal', 'Rideout, Bruce']",,,,
,PMC,Evaluation of Real-Time Reverse Transcriptase PCR and Real-Time Loop-Mediated Amplification Assays for Severe Acute Respiratory Syndrome Coronavirus Detection,http://dx.doi.org/10.1128/JCM.43.7.3457-3459.2005,PMC1169087,,,"We compared the performance of a recently established real-time loop-mediated amplification (LAMP) assay with the one from a highly sensitive quantitative PCR assay. None of these assays produced false-positive results in this study. For samples isolated from patients within the first 3 days of disease onset, the detection rate of the quantitative PCR assay was higher (14 of 15 were positive) than the LAMP assay (9 of 15 were positive). By contrast, the detection rates of these assays toward specimens sampled from patients with more than 3 days of illness were similar (32 of 44 for PCR and 33 of 44 for LAMP were positive). The simpler operation of LAMP might be a possible solution for on-site diagnosis.",,"['Poon, Leo L. M.', 'Wong, Bonnie W. Y.', 'Chan, Kwok H.', 'Ng, Stella S. F.', 'Yuen, Kwok Y.', 'Guan, Yi', 'Peiris, J. S. Malik']",,,,
,PMC,Novel Innate Immune Functions for Galectin-1: Galectin-1 Inhibits Cell Fusion by Nipah Virus Envelope Glycoproteins and Augments Dendritic Cell Secretion of Proinflammatory Cytokines(),,PMC4428613,,,"Galectin-1 (gal-1), an endogenous lectin secreted by a variety of cell types, has pleiotropic immunomodulatory functions, including regulation of lymphocyte survival and cytokine secretion in autoimmune, transplant disease, and parasitic infection models. However, the role of gal-1 in viral infections is unknown. Nipah virus (NiV) is an emerging pathogen that causes severe, often fatal, febrile encephalitis. The primary targets of NiV are endothelial cells. NiV infection of endothelial cells results in cell-cell fusion and syncytia formation triggered by the fusion (F) and attachment (G) envelope glycoproteins of NiV that bear glycan structures recognized by gal-1. In the present study, we report that NiV envelope-mediated cell-cell fusion is blocked by gal-1. This inhibition is specific to the Paramyxoviridae family because gal-1 did not inhibit fusion triggered by envelope glycoproteins of other viruses, including two retroviruses and a pox virus, but inhibited fusion triggered by envelope glycoproteins of the related Hendra virus and another paramyxovirus. The physiologic dimeric form of gal-1 is required for fusion inhibition because a monomeric gal-1 mutant had no inhibitory effect on cell fusion. gal-1 binds to specific N-glycans on NiV glycoproteins and aberrantly oligomerizes NiV-F and NiV-G, indicating a mechanism for fusion inhibition. gal-1 also increases dendritic cell production of proinflammatory cytokines such as IL-6, known to be protective in the setting of other viral diseases such as Ebola infections. Thus, gal-1 may have direct antiviral effects and may also augment the innate immune response against this emerging pathogen.",,"['Levroney, Ernest L.', 'Aguilar, Hector C.', 'Fulcher, Jennifer A.', 'Kohatsu, Luciana', 'Pace, Karen E.', 'Pang, Mabel', 'Gurney, Kevin B.', 'Baum, Linda G.', 'Lee, Benhur']",,,,
,PMC,Contributions of the Viral Genetic Background and a Single Amino Acid Substitution in an Immunodominant CD8(+) T-Cell Epitope to Murine Coronavirus Neurovirulence,http://dx.doi.org/10.1128/JVI.79.14.9108-9118.2005,PMC1168726,,,"The immunodominant CD8(+) T-cell epitope of a highly neurovirulent strain of mouse hepatitis virus (MHV), JHM, is thought to be essential for protection against virus persistence within the central nervous system. To test whether abrogation of this H-2D(b)-restricted epitope, located within the spike glycoprotein at residues S510 to 518 (S510), resulted in delayed virus clearance and/or virus persistence we selected isogenic recombinants which express either the wild-type JHM spike protein (RJHM) or spike containing the N514S mutation (RJHM(N514S)), which abrogates the response to S510. In contrast to observations in suckling mice in which viruses encoding inactivating mutations within the S510 epitope (epitope escape mutants) were associated with persistent virus and increased neurovirulence (Pewe et al., J Virol. 72:5912-5918, 1998), RJHM(N514S) was not more virulent than the parental, RJHM, in 4-week-old C57BL/6 (H-2(b)) mice after intracranial injection. Recombinant viruses expressing the JHM spike, wild type or encoding the N514S substitution, were also selected in which background genes were derived from the neuroattenuated A59 strain of MHV. Whereas recombinants expressing the wild-type JHM spike (SJHM/RA59) were highly neurovirulent, A59 recombinants containing the N514S mutation (SJHM(N514S)/RA59) were attenuated, replicated less efficiently, and exhibited reduced virus spread in the brain at 5 days postinfection (peak of infectious virus titers in the central nervous system) compared to parental virus encoding wild-type spike. Virulence assays in BALB/c mice (H-2(d)), which do not recognize the S510 epitope, revealed that attenuation of the epitope escape mutants was not due to the loss of a pathogenic immune response directed against the S510 epitope. Thus, an intact immunodominant S510 epitope is not essential for virus clearance from the CNS, the S510 inactivating mutation results in decreased virulence in weanling mice but not in suckling mice, suggesting that specific host conditions are required for epitope escape mutants to display increased virulence, and the N514S mutation causes increased attenuation in the context of A59 background genes, demonstrating that genes other than that for the spike are also important in determining neurovirulence.",,"['MacNamara, Katherine C.', 'Chua, Ming Ming', 'Phillips, Joanna J.', 'Weiss, Susan R.']",,,,
,PMC,Gene 5 of the Avian Coronavirus Infectious Bronchitis Virus Is Not Essential for Replication,http://dx.doi.org/10.1128/JVI.79.13.8065-8078.2005,PMC1143771,,,"The avian coronavirus Infectious bronchitis virus (IBV), like other coronaviruses, expresses several small nonstructural (ns) proteins in addition to those from gene 1 (replicase) and the structural proteins. These coronavirus ns genes differ both in number and in amino acid similarity between the coronavirus groups but show some concordance within a group or subgroup. The functions and requirements of the small ns gene products remain to be elucidated. With the advent of reverse genetics for coronaviruses, the first steps in elucidating their role can be investigated. We have used our reverse genetics system for IBV (R. Casais, V. Thiel, S. G. Siddell, D. Cavanagh, and P. Britton, J. Virol. 75:12359-12369, 2001) to investigate the requirement of IBV gene 5 for replication in vivo, in ovo, and ex vivo. We produced a series of recombinant viruses, with an isogenic background, in which complete expression of gene 5 products was prevented by the inactivation of gene 5 following scrambling of the transcription-associated sequence, thereby preventing the expression of IBV subgenomic mRNA 5, or scrambling either separately or together of the translation initiation codons for the two gene 5 products. As all of the recombinant viruses replicated very similarly to the wild-type virus, Beau-R, we conclude that the IBV gene 5 products are not essential for IBV replication per se and that they are accessory proteins.",,"['Casais, Rosa', 'Davies, Marc', 'Cavanagh, David', 'Britton, Paul']",,,,
,PMC,Torovirus Non-Discontinuous Transcription: Mutational Analysis of a Subgenomic mRNA Promoter,http://dx.doi.org/10.1128/JVI.79.13.8275-8281.2005,PMC1143767,,,"Toroviruses (order Nidovirales) are enveloped positive-strand RNA viruses of mammals. The prototype torovirus, equine torovirus strain Berne (Berne virus [BEV]), uses two different transcription strategies to produce a 3′-coterminal nested set of subgenomic (sg) mRNAs. Its mRNA 2 carries a leader sequence derived from the 5′ end of the genome and is produced via discontinuous transcription. The remaining three sg mRNAs, 3 to 5, are colinear with the 3′ end of the genome and are made via non-discontinuous RNA synthesis. Their synthesis is supposedly regulated by short conserved sequence motifs, 5′-ACN(3-4)CUUUAGA-3′, within the noncoding intergenic regions that precede the M, HE, and N genes (A. L. van Vliet, S. L. Smits, P. J. Rottier, and R. J. de Groot, EMBO J. 21:6571-6580, 2002). We have now studied the—for nidoviruses unusual—non-discontinuous transcription mechanism in further detail by probing the role of the postulated transcription-regulating sequences (TRSs). To this end, we constructed a synthetic defective interfering (DI) RNA, carrying a 24-nucleotide segment of the intergenic region between the HE and N genes. We demonstrate that this DI RNA, when introduced into BEV-infected cells, directs the synthesis of a sg DI RNA species; in fact, a 16-nucleotide cassette containing the TRS already proved sufficient. Synthesis of this sg DI RNA, like that of mRNAs 3 to 5 of the standard virus, initiated at the 5′-most adenylate of the TRS. An extensive mutational analysis of the TRS is presented. Our results provide first and formal experimental evidence that the conserved motifs within the BEV intergenic sequences indeed drive sg RNA synthesis.",,"['Smits, Saskia L.', 'van Vliet, Arno L. W.', 'Segeren, Katja', 'el Azzouzi, Hamid', 'van Essen, Maarten', 'de Groot, Raoul J.']",,,,
,PMC,Herpes Simplex Virus ICP27 Activation of Stress Kinases JNK and p38,http://dx.doi.org/10.1128/JVI.79.13.8348-8360.2005,PMC1143742,,,"We previously reported that herpes simplex virus type 1 (HSV-1) can activate the stress-activated protein kinases (SAPKs) p38 and JNK. In the present study, we undertook a comprehensive and comparative analysis of the requirements for viral protein synthesis in the activation of JNK and p38. Infection with the UL36 mutant tsB7 or with UV-irradiated virus indicated that both JNK and p38 activation required viral gene expression. Cycloheximide reversal or phosphonoacetic acid treatment of wild-type virus-infected cells as well as infection with the ICP4 mutant vi13 indicated that only the immediate-early class of viral proteins were required for SAPK activation. Infection with ICP4, ICP27, or ICP0 mutant viruses indicated that only ICP27 was necessary. Additionally, we determined that in the context of virus infection ICP27 was sufficient for SAPK activation and activation of the p38 targets Mnk1 and MK2 by infecting with mutants deleted for various combinations of immediate-early proteins. Specifically, the d100 (0(−)/4(−)) and d103 (4(−)/22(−)/47(−)) mutants activated p38 and JNK, while the d106 (4(−)/22(−)/27(−)/47(−)) and d107 (4(−)/27(−)) mutants did not. Finally, infections with a series of ICP27 mutants demonstrated that the functional domain of ICP27 required for activation was located in the region encompassing amino acids 20 to 65 near the N terminus of the protein and that the C-terminal transactivation activity of ICP27 was not necessary.",,"['Hargett, Danna', 'McLean, Tim', 'Bachenheimer, Steven L.']",,,,
,PMC,New DNA Viruses Identified in Patients with Acute Viral Infection Syndrome,http://dx.doi.org/10.1128/JVI.79.13.8230-8236.2005,PMC1143717,,,"A sequence-independent PCR amplification method was used to identify viral nucleic acids in the plasma samples of 25 individuals presenting with symptoms of acute viral infection following high-risk behavior for human immunodeficiency virus type 1 transmission. GB virus C/hepatitis G virus was identified in three individuals and hepatitis B virus in one individual. Three previously undescribed DNA viruses were also detected, a parvovirus and two viruses related to TT virus (TTV). Nucleic acids in human plasma that were distantly related to bacterial sequences or with no detectable similarities to known sequences were also found. Nearly complete viral genome sequencing and phylogenetic analysis confirmed the presence of a new parvovirus distinct from known human and animal parvoviruses and of two related TTV-like viruses highly divergent from both the TTV and TTV-like minivirus groups. The detection of two previously undescribed viral species in a small group of individuals presenting acute viral syndrome with unknown etiology indicates that a rich yield of new human viruses may be readily identifiable using simple methods of sequence-independent nucleic acid amplification and limited sequencing.",,"['Jones, Morris S.', 'Kapoor, Amit', 'Lukashov, Vladimir V.', 'Simmonds, Peter', 'Hecht, Frederick', 'Delwart, Eric']",,,,
,PMC,Histidine at Residue 99 and the Transmembrane Region of the Precursor Membrane prM Protein Are Important for the prM-E Heterodimeric Complex Formation of Japanese Encephalitis Virus,http://dx.doi.org/10.1128/JVI.79.13.8535-8544.2005,PMC1143704,,,"The formation of the flavivirus prM-E complex is an important step for the biogenesis of immature virions, which is followed by a subsequent cleavage of prM to M protein through cellular protease to result in the production and release of mature virions. In this study, the intracellular formation of the prM-E complex of Japanese encephalitis virus was investigated by baculovirus coexpression of prM and E in trans in Sf9 insect cells as analyzed by anti-E antibody immunoprecipitation and sucrose gradient sedimentation analysis. A series of carboxyl-terminally truncated prM mutant baculoviruses was constructed to demonstrate that the truncations of the transmembrane (TM) region resulted in a reduction of the formation of the stable prM-E complex by approximately 40% for the TM1 (at residues 130 to 147 [prM130-147]) truncation and 20% for TM2 (at prM153-167) truncation. Alanine-scanning site-directed mutagenesis on the prM99-103 region indicated that the His99 residue was the critical prM binding element for stable prM-E heterodimeric complex formation. The single amino acid mutation at the His99 residue of prM abolishing the prM-E interaction was not due to reduced expression or different subcellular location of the mutant prM protein involved in prM-E interactions as characterized by pulse-chase labeling and confocal scanning microscopic analysis. Recombinant subviral particles were detected in the Sf9 cell culture supernatants by baculovirus coexpression of prM and E proteins but not with the prM H99A mutant. Sequence alignment analysis was further conducted with different groups of flaviviruses to show that the prM H99 residues are generally conserved. Our findings are the first report to characterize the minimum binding elements of the prM protein that are involved in prM-E interactions of flaviviruses. This information, concerning a molecular framework for the prM protein, is considered to elucidate the structure/function relationship of the prM-E complex synthesis and provide the proper trajectory for flavivirus assembly and maturation.",,"['Lin, Ying-Ju', 'Wu, Suh-Chin']",,,,
,PMC,Impact of a Spreading Epidemic on Medical Students,,PMC3349400,,,"The emergence of severe acute respiratory syndrome (SARS) had caused fear and anxiety of unprecedented proportion. To examine the impact of SARS on the medical students in a private medical university, a self-reporting questionnaire study was carried out to assess the factual knowledge, anxiety level and perception of the crisis, among the students. The two-week study (between 12 and 23 May, 2003) was carried out three weeks after the first reported SARS-related death in Malaysia. Ninety-one Phase I (junior) and 113 Phase II (senior) students completed the questionnaires. A large majority of students of Phase I and II were correct in their factual knowledge and were sensible in their perception of the future and the handling of the crisis by government(s). However, phase 1 students expressed significantly greater degree of anxiety compared to Phase II in relation to attendance and personal protection in hospital, and in meeting people coughing in public places. The lesser degree of anxiety expressed by phase II senior students may be due in part, to a more realistic assessment of SARS risk brought about by maturity, time spent in hospital and interaction with clinical lecturers and medical staff.",,"['Loh, Li-Cher', 'Ali, Anita Mohd', 'Ang, Ter-Hoay', 'Chelliah, Ambiga']",,,,
,PMC,Appropriate use of personal protective equipment among healthcare workers in public sector hospitals and primary healthcare polyclinics during the SARS outbreak in Singapore,http://dx.doi.org/10.1136/oem.2004.015024,PMC1741057,,,"Background: Singapore was affected by an outbreak of severe acute respiratory syndrome (SARS) from 25 February to 31 May 2003, with 238 probable cases and 33 deaths. Aims: To study usage of personal protective equipment (PPE) among three groups of healthcare workers (HCWs: doctors, nurses, and administrative staff), to determine if the appropriate PPE were used by the different groups and to examine the factors that may determine inappropriate use. Methods: A self-administered questionnaire survey of 14 554 HCWs in nine healthcare settings, which included tertiary care hospitals, community hospitals, and polyclinics, was carried out in May–July 2003. Only doctors, nurses, and clerical staff were selected for subsequent analysis. Results: A total of 10 236 valid questionnaires were returned (70.3% response); 873 doctors, 4404 nurses, and 921 clerical staff were studied. A total of 32.5% of doctors, 48.7% of nurses, and 77.1% of the administrative staff agreed that paper and/or surgical masks were ""useful in protecting from contracting SARS"". Among this group, 23.6% of doctors and 42.3% of nurses reported working with SARS patients. The view that a paper and/or surgical mask was adequate protection against SARS was held by 33.3% of doctors and 55.9% of nurses working at the A&E unit, 30.5% of doctors and 49.4% of nurses from medical wards, and 27.5% of doctors and 37.1% of nurses from intensive care units. Factors which predicted for agreement that paper and/or surgical masks were protective against SARS, included HCW's job title, reported contact with SARS patients, area of work, and Impact Events Scale scores. Conclusion: A variety of factors determine appropriate use of personal protective equipment by HCWs in the face of a major SARS outbreak.",,"['Chia, S', 'Koh, D', 'Fones, C', 'Qian, F', 'Ng, V', 'Tan, B', 'Wong, K', 'Chew, W', 'Tang, H', 'Ng, W', 'Muttakin, Z', 'Emmanuel, S', 'Fong, N', 'Koh, G', 'Lim, M']",,,,
,PMC,Paediatric research in Canada: 2000–2004,,PMC2722969,,,,,"Gold, Ronald",,,,
,PMC,Recovery of the ciliated epithelium following acute bronchiolitis in infancy,http://dx.doi.org/10.1136/thx.2004.024638,PMC1747455,,,"Background: Little is known about the longitudinal changes in the ciliated respiratory epithelium of infants following viral bronchiolitis. A study was undertaken to investigate the time required for the ciliated epithelium to return to normal following bronchiolitis in infants treated with inhaled steroids or placebo. Methods: Thirty one previously healthy term infants were studied as part of a clinical trial to determine the effect of 12 weeks of treatment with inhaled fluticasone (FP) or placebo via a spacer device (17 FP, 14 placebo). Nineteen healthy children aged 0–6 years previously studied in our department were used as controls. Nasal biopsy specimens were taken from infants with bronchiolitis and ciliary beat frequency (CBF) was measured before treatment and repeated 3, 6, 12, and 24 weeks later. The epithelial ultrastructure was examined by transmission electron microscopy and a normal errors mixed model based on normal controls was used to examine the time for cilia to return to normal in bronchiolitic infants. Results: The mean CBF of infants with bronchiolitis (in Hz) at weeks 0, 3, 6, 12, and 24 were 0.5 (n = 4), 10.9 (n = 4), 12.0 (n = 9), 11.9 (n = 8), and 12.1 (n = 7) in the placebo group and 10.6 (n = 6), 11.4 (n = 9), 8.8 (n = 8), 10.9 (n = 4), and 13.2 (n = 7) in the FP group. The time for the epithelial ultrastructure to normalise was as follows: epithelial integrity score (13.1 weeks), % ciliated cells with loss of cilia (14.0 weeks), and % epithelial cells with abnormalities in projection (16.7 weeks) or mitochondria (15.9 weeks). Inhaled steroids had no significant effects on CBF or epithelial ultrastructure. Conclusion: Ciliary loss and epithelial abnormalities persist on average for 13–17 weeks following acute bronchiolitis in infancy.",,"['Wong, J', 'Rutman, A', ""O'Callaghan, C""]",,,,
,PMC,Disease contact tracing in random and clustered networks,http://dx.doi.org/10.1098/rspb.2005.3092,PMC1560336,,,"The efficacy of contact tracing, be it between individuals (e.g. sexually transmitted diseases or severe acute respiratory syndrome) or between groups of individuals (e.g. foot-and-mouth disease; FMD), is difficult to evaluate without precise knowledge of the underlying contact structure; i.e. who is connected to whom? Motivated by the 2001 FMD epidemic in the UK, we determine, using stochastic simulations and deterministic ‘moment closure’ models of disease transmission on networks of premises (nodes), network and disease properties that are important for contact tracing efficiency. For random networks with a high average number of connections per node, little clustering of connections and short latency periods, contact tracing is typically ineffective. In this case, isolation of infected nodes is the dominant factor in determining disease epidemic size and duration. If the latency period is longer and the average number of connections per node small, or if the network is spatially clustered, then the contact tracing performs better and an overall reduction in the proportion of nodes that are removed during an epidemic is observed.",,"['Kiss, Istvan Z', 'Green, Darren M', 'Kao, Rowland R']",,,,
,PMC,SARS changed medical dress code,,PMC558424,,,,,"Au-Yeung, Peter K K",,,,
,PMC,Severe acute respiratory syndrome (SARS) S protein production in plants: Development of recombinant vaccine,http://dx.doi.org/10.1073/pnas.0503760102,PMC1157057,,,"In view of a recent spread of severe acute respiratory syndrome (SARS), there is a high demand for production of a vaccine to prevent this disease. Recent studies indicate that SARS-coronavirus (CoV) spike protein (S protein) and its truncated fragments are considered the best candidates for generation of the recombinant vaccine. Toward the development of a safe, effective, and inexpensive vaccine candidate, we have expressed the N-terminal fragment of SARS-CoV S protein (S1) in tomato and low-nicotine tobacco plants. Incorporation of the S1 fragment into plant genomes as well as its transcription was confirmed by PCR and RT-PCR analyses. High levels of expression of recombinant S1 protein were observed in several transgenic lines by Western blot analysis using specific antibodies. Plant-derived antigen was evaluated to induce the systemic and mucosal immune responses in mice. Mice showed significantly increased levels of SARS-CoV-specific IgA after oral ingestion of tomato fruits expressing S1 protein. Sera of mice parenterally primed with tobacco-derived S1 protein revealed the presence of SARS-CoV-specific IgG as detected by Western blot and ELISA analysis.",,"['Pogrebnyak, Natalia', 'Golovkin, Maxim', 'Andrianov, Vyacheslav', 'Spitsin, Sergei', 'Smirnov, Yuriy', 'Egolf, Richard', 'Koprowski, Hilary']",,,,
,PMC,Perspectives on the basic reproductive ratio,http://dx.doi.org/10.1098/rsif.2005.0042,PMC1578275,,,"The basic reproductive ratio, R(0), is defined as the expected number of secondary infections arising from a single individual during his or her entire infectious period, in a population of susceptibles. This concept is fundamental to the study of epidemiology and within-host pathogen dynamics. Most importantly, R(0) often serves as a threshold parameter that predicts whether an infection will spread. Related parameters which share this threshold behaviour, however, may or may not give the true value of R(0). In this paper we give a brief overview of common methods of formulating R(0) and surrogate threshold parameters from deterministic, non-structured models. We also review common means of estimating R(0) from epidemiological data. Finally, we survey the recent use of R(0) in assessing emerging diseases, such as severe acute respiratory syndrome and avian influenza, a number of recent livestock diseases, and vector-borne diseases malaria, dengue and West Nile virus.",,"['Heffernan, J.M', 'Smith, R.J', 'Wahl, L.M']",,,,
,PMC,This Week in PNAS,http://dx.doi.org/10.1073/iti2305102,PMC1149456,,,,,,,,,
,PMC,Three-dimensional structure of the bacteriophage P22 tail machine,http://dx.doi.org/10.1038/sj.emboj.7600695,PMC1150889,,,"The tail of the bacteriophage P22 is composed of multiple protein components and integrates various biological functions that are crucial to the assembly and infection of the phage. The three-dimensional structure of the P22 tail machine determined by electron cryo-microscopy and image reconstruction reveals how the five types of polypeptides present as 51 subunits are organized into this molecular machine through twelve-, six- and three-fold symmetry, and provides insights into molecular events during host cell attachment and phage DNA translocation.",,"['Tang, Liang', 'Marion, William R', 'Cingolani, Gino', 'Prevelige, Peter E', 'Johnson, John E']",,,,
,PMC,Immune Regulatory Mechanisms Influence Early Pathology in Spinal Cord Injury and in Spontaneous Autoimmune Encephalomyelitis,,PMC1602407,,,"Injuries to the central nervous system (CNS) trigger an inflammatory reaction with potentially devastating consequences. In this report we compared the characteristics of the inflammatory response on spinal cord injury (SCI) caused by a stab wound between the T7 and T9 vertebrae and spontaneous experimental autoimmune encephalomyelitis (EAE). SCI and EAE were compared in two types of myelin basic protein Ac1-11-specific T-cell receptor transgenic mice: T/R(+) mice harbor regulatory T cells, and T/R(−) mice lack regulatory T cells. Our results show that 8 days after SCI, T/R(−) mice developed a strong T-cell infiltrate in the spinal cord, with remarkable down-modulation of CD4 expression that was accompanied by a local increase in Mac-3(+) and F4/80(+) reactivity and diffuse local and distal astrogliosis. In contrast, T/R(+) mice exhibited a modest increase in CD4(+) cells localized to the site of injury, without CD4 down-modulation; focal astrogliosis was restricted to the site of the lesion, although Mac-3(+) and F4/80(+) cells were also present. Similarly to T/R(−) mice that underwent SCI, T cells displaying down-modulated CD4 expression were found in the CNS of older T/R(−) mice afflicted by spontaneous EAE. Overall, our results suggest that common mechanisms regulate T-cell accumulation in CNS lesions of different causes, such as mechanic lesion or autoimmune-mediated damage.",,"['Marcondes, Maria Cecilia G.', 'Furtado, Glaucia C.', 'Wensky, Allen', 'Curotto de Lafaille, Maria A.', 'Fox, Howard S.', 'Lafaille, Juan J.']",,,,
,PMC,CHANG AND HUANG RESPOND,http://dx.doi.org/10.2105/AJPH.2004.046839,PMC1449284,,,,,"['Chang, Hong-Jen', 'Huang, Nicole']",,,,
,PMC,LOWERED TUBERCULOSIS NOTIFICATIONS AND DETERRED HEALTH CARE SEEKING DURING THE SARS EPIDEMIC IN HONG KONG,http://dx.doi.org/10.2105/AJPH.2004.046763,PMC1449283,,,,,"['Ichikawa, Masao', 'Nakahara, Shinji', 'Wakai, Susumu']",,,,
,PMC,"The Spatial Dynamics of Poliomyelitis in the United States: From Epidemic Emergence to Vaccine-Induced Retreat, 1910–1971",http://dx.doi.org/10.1111/j.1467-8306.2005.00460.x,PMC1473032,,,"This article seeks to advance an understanding of the spatial dynamics of one of the great emergent viral diseases of the twentieth century—poliomyelitis. From an apparently rare clinical condition occurring only sporadically or in small outbreaks before the late nineteenth century, poliomyelitis had, by the early 1950s, developed into a globally distributed epidemic disease. But, from 1955, continued growth was suddenly and dramatically reversed by the mass administration of inactivated (killed) and live (attenuated) poliovirus vaccines. After almost half a century of vaccine control, the world now stands on the brink of the global eradication of the disease. Against this background, the article draws upon information included in the U.S. Public Health Service’s Public Health Reports and the U.S. Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report to examine the spatial dynamics of poliomyelitis during the phases of epidemic emergence (1910–1955) and vaccine-induced retreat (1955–1971) in the United States. It is shown that epidemic emergence was accompanied by shifts in the spatial center of activity from early diffusion poles in the northeastern states, to the western seaboard, and then finally to cover all the states of the Union. This was accompanied by accelerating epidemic propagation. The introduction of mass vaccination from the mid-1950s realigned spatial transmission of the disease, producing increased spatial volatility in the geographical center of activity and heightened dependence of epidemic outbreaks upon endemic reservoirs in the most populous states. Finally, the empirical results are generalized to suggest that the emergence and reemergence of many infectious diseases is a distinctively geographical process.",,"['Trevelyan, Barry', 'Smallman-Raynor, Matthew', 'Cliff, Andrew D.']",,,,
,PMC,Phosphorylation of Ribavirin and Viramidine by Adenosine Kinase and Cytosolic 5′-Nucleotidase II: Implications for Ribavirin Metabolism in Erythrocytes,http://dx.doi.org/10.1128/AAC.49.6.2164-2171.2005,PMC1140532,,,"Many nucleoside analog drugs, such as ribavirin and viramidine, are activated or metabolized in vivo through 5′-phosphorylation. In this report, we determined the steady-state kinetic parameters for 5′-monophosphorylation of ribavirin and viramidine by adenosine kinase. The apparent K(m) for ribavirin is 540 μM, and k(cat) is 1.8 min(−1). Its catalytic efficiency of 3.3 × 10(−3) min(−1) · μM(−1) is 1,200-fold lower than that of adenosine. In contrast to the common belief that ribavirin is exclusively phosphorylated by adenosine kinase, cytosolic 5′-nucleotidase II was found to catalyze ribavirin phosphorylation in vitro. The reaction is optimally stimulated by the physiological concentration of ATP or 2,3-bisphosphoglycerate. In phosphate-buffered saline plus ATP and 2,3-bisphosphoglycerate, the apparent K(m) for ribavirin is 88 μM, and k(cat) is 4.0 min(−1). These findings suggest that cytosolic 5′-nucleotidase II may be involved in ribavirin phosphorylation in vivo. Like ribavirin, viramidine was found to be phosphorylated by either adenosine kinase or cytosolic 5′-nucleotidase II, albeit with a much lower activity. The catalytic efficiency for viramidine phosphorylation is 10- to 330-fold lower than that of ribavirin, suggesting that other nucleoside kinase(s) may be involved in viramidine phosphorylation in vivo. Both ribavirin and viramidine are not phosphorylated by deoxycytidine kinase and uridine-cytidine kinase. The coincidence of presence of high concentrated 2,3-bisphosphoglycerate in erythrocytes suggests that cytosolic 5′-nucleotidase II could play an important role in phosphorylating ribavirin and contribute to anabolism of ribavirin triphosphate in erythrocytes. Elucidation of ribavirin and viramidine phosphorylation mechanism should shed light on their in vivo metabolism, especially the ribavirin-induced hemolytic anemia in erythrocytes.",,"['Wu, Jim Zhen', 'Larson, Gary', 'Walker, Heli', 'Shim, Jae Hoon', 'Hong, Zhi']",,,,
,PMC,Human metapneumovirus infection in children hospitalized for wheezing,http://dx.doi.org/10.1016/j.jaci.2005.02.001,PMC1476700,,,,,"['Williams, John V.', 'Tollefson, Sharon J.', 'Heymann, Peter W.', 'Carper, Holliday T.', 'Patrie, James', 'Crowe, James E.']",,,,
,PMC,"Integrative Genomic, Transcriptional, and Proteomic Diversity in Natural Isolates of the Human Pathogen Burkholderia pseudomallei",http://dx.doi.org/10.1128/JB.187.12.4276-4285.2005,PMC1151743,,,"Natural isolates of pathogenic bacteria can exhibit a broad range of phenotypic traits. To investigate the molecular mechanisms contributing to such phenotypic variability, we compared the genomes, transcriptomes, and proteomes of two natural isolates of the gram-negative bacterium Burkholderia pseudomallei, the causative agent of the human disease melioidosis. Significant intrinsic genomic, transcriptional, and proteomic variations were observed between the two strains involving genes of diverse functions. We identified 16 strain-specific regions in the B. pseudomallei K96243 reference genome, and for eight regions their differential presence could be ascribed to either DNA acquisition or loss. A remarkable 43% of the transcriptional differences between the strains could be attributed to genes that were differentially present between K96243 and Bp15682, demonstrating the importance of lateral gene transfer or gene loss events in contributing to pathogen diversity at the gene expression level. Proteins expressed in a strain-specific manner were similarly correlated at the gene expression level, but up to 38% of the global proteomic variation between strains comprised proteins expressed in both strains but associated with strain-specific protein isoforms. Collectively, >65 hypothetical genes were transcriptionally or proteomically expressed, supporting their bona fide biological presence. Our results provide, for the first time, an integrated framework for classifying the repertoire of natural variations existing at distinct molecular levels for an important human pathogen.",,"['Ou, Keli', 'Ong, Catherine', 'Koh, Shze Yung', 'Rodrigues, Fiona', 'Sim, Siew Hoon', 'Wong, Daniel', 'Ooi, Chia Huey', 'Ng, Kim Chong', 'Jikuya, Hiroyuki', 'Yau, Chin Chin', 'Soon, Sou Yen', 'Kesuma, Djohan', 'Lee, May Ann', 'Tan, Patrick']",,,,
,PMC,"Identification, Molecular Characterization, and Experimental Transmission of a New Hemoplasma Isolate from a Cat with Hemolytic Anemia in Switzerland",http://dx.doi.org/10.1128/JCM.43.6.2581-2585.2005,PMC1151947,,,"Recently, there has been a growing interest in hemotropic mycoplasmal species (also known as the hemoplasmas), the causative agents of infectious anemia in several mammalian species. In felids, two different hemoplasma species have been recognized: Mycoplasma haemofelis (formerly Haemobartonella felis) and “Candidatus Mycoplasma haemominutum.” Recently developed molecular methods have allowed sensitive and specific identification and quantification of these agents in feline blood samples. In applying these methods to an epidemiological study surveying the Swiss pet cat population for hemoplasma infection, we discovered a third novel and unique feline hemoplasma isolate in a blood sample collected from a cat that had exhibited clinical signs of severe hemolytic anemia. This agent was readily transmitted via intravenous inoculation to two specific-pathogen-free cats. One of these cats was immunocompromised by the administration of methylprednisolone acetate prior to inoculation, and this cat developed severe anemia. The other immunocompetent cat showed a moderate decrease in packed cell volume. Additionally, an increase in red blood cell osmotic fragility was observed. Sequencing of the entire 16S rRNA gene of the new hemoplasma isolate and phylogenetic analysis showed that the isolate was most closely related to two rodent hemotropic mycoplasmal species, M. coccoides and M. haemomuris. A quantitative real-time PCR assay specific for this newly discovered agent was developed, which will be a prerequisite for the diagnosis of infections with the new hemoplasma isolate.",,"['Willi, Barbara', 'Boretti, Felicitas S.', 'Cattori, Valentino', 'Tasker, Séverine', 'Meli, Marina L.', 'Reusch, Claudia', 'Lutz, Hans', 'Hofmann-Lehmann, Regina']",,,,
,PMC,Rapid Detection and Differentiation of Dengue Virus Serotypes by a Real-Time Reverse Transcription-Loop-Mediated Isothermal Amplification Assay,http://dx.doi.org/10.1128/JCM.43.6.2895-2903.2005,PMC1151941,,,"The development and validation of a one-step, real-time, and quantitative dengue virus serotype-specific reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay targeting the 3′ noncoding region for the rapid detection and differentiation of dengue virus serotypes are reported. The RT-LAMP assay is very simple and rapid, wherein the amplification can be obtained in 30 min under isothermal conditions at 63°C by employing a set of four serotype-specific primer mixtures through real-time monitoring in an inexpensive turbidimeter. The evaluation of the RT-LAMP assay for use for clinical diagnosis with a limited number of patient serum samples, confirmed to be infected with each serotype, revealed a higher sensitivity by picking up 100% samples as positive, whereas 87% and 81% of the samples were positive by reverse transcription-PCR and virus isolation, respectively. The sensitivity and specificity of the RT-LAMP assay for the detection of viral RNA in patient serum samples with reference to virus isolation were 100% and 93%, respectively. The optimal assay conditions with zero background and no cross-reaction with other closely related members of the Flavivirus family (Japanese encephalitis, West Nile, and St. Louis encephalitis viruses) as well as within the four serotypes of dengue virus were established. None of the serum samples from healthy individuals screened in this study showed any cross-reaction with the four dengue virus serotype-specific RT-LAMP assay primers. These findings demonstrate that RT-LAMP assay has the potential clinical application for detection and differentiation of dengue virus serotypes, especially in developing countries.",,"['Parida, Manmohan', 'Horioke, Kouhei', 'Ishida, Hiroyuki', 'Dash, Paban Kumar', 'Saxena, Parag', 'Jana, Asha Mukul', 'Islam, Mohammed Alimul', 'Inoue, Shingo', 'Hosaka, Norimitsu', 'Morita, Kouichi']",,,,
,PMC,Dissemination of Multisusceptible Methicillin-Resistant Staphylococcus aureus in Singapore,http://dx.doi.org/10.1128/JCM.43.6.2923-2925.2005,PMC1151929,,,Analysis of hospital-acquired methicillin-resistant Staphylococcus aureus strains isolated from a tertiary public hospital in Singapore revealed that multisusceptible strains had gradually started to replace the endemic multiresistant strain (ST239-MRSA-III) since 2002. Molecular typing showed that this was a predominantly clonal outbreak of a UK-EMRSA-15 strain (ST22-MRSA-IV).,,"['Hsu, Li-Yang', 'Koh, Tse-Hsien', 'Singh, Kamaljit', 'Kang, Mei-Ling', 'Kurup, Asok', 'Tan, Ban-Hock']",,,,
,PMC,Complement Activation Is Required for Induction of a Protective Antibody Response against West Nile Virus Infection,http://dx.doi.org/10.1128/JVI.79.12.7466-7477.2005,PMC1143684,,,"Infection with West Nile virus (WNV) causes a severe infection of the central nervous system (CNS) with higher levels of morbidity and mortality in the elderly and the immunocompromised. Experiments with mice have begun to define how the innate and adaptive immune responses function to limit infection. Here, we demonstrate that the complement system, a major component of innate immunity, controls WNV infection in vitro primarily in an antibody-dependent manner by neutralizing virus particles in solution and lysing WNV-infected cells. More decisively, mice that genetically lack the third component of complement or complement receptor 1 (CR1) and CR2 developed increased CNS virus burdens and were vulnerable to lethal infection at a low dose of WNV. Both C3-deficient and CR1- and CR2-deficient mice also had significant deficits in their humoral responses after infection with markedly reduced levels of specific anti-WNV immunoglobulin M (IgM) and IgG. Overall, these results suggest that complement controls WNV infection, in part through its ability to induce a protective antibody response.",,"['Mehlhop, Erin', 'Whitby, Kevin', 'Oliphant, Theodore', 'Marri, Anantha', 'Engle, Michael', 'Diamond, Michael S.']",,,,
,PMC,Murine Coronavirus Evolution In Vivo: Functional Compensation of a Detrimental Amino Acid Substitution in the Receptor Binding Domain of the Spike Glycoprotein,http://dx.doi.org/10.1128/JVI.79.12.7629-7640.2005,PMC1143675,,,"Murine coronavirus A59 strain causes mild to moderate hepatitis in mice. We have previously shown that mutants of A59, unable to induce hepatitis, may be selected by persistent infection of primary glial cells in vitro. These in vitro isolated mutants encoded two amino acids substitutions in the spike (S) gene: Q159L lies in the putative receptor binding domain of S, and H716D, within the cleavage signal of S. Here, we show that hepatotropic revertant variants may be selected from these in vitro isolated mutants (Q159L-H716D) by multiple passages in the mouse liver. One of these mutants, hr2, was chosen for more in-depth study based on a more hepatovirulent phenotype. The S gene of hr2 (Q159L-R654H-H716D-E1035D) differed from the in vitro isolates (Q159L-H716D) in only 2 amino acids (R654H and E1035D). Using targeted RNA recombination, we have constructed isogenic recombinant MHV-A59 viruses differing only in these specific amino acids in S (Q159L-R654H-H716D-E1035D). We demonstrate that specific amino acid substitutions within the spike gene of the hr2 isolate determine the ability of the virus to cause lethal hepatitis and replicate to significantly higher titers in the liver compared to wild-type A59. Our results provide compelling evidence of the ability of coronaviruses to rapidly evolve in vivo to highly virulent phenotypes by functional compensation of a detrimental amino acid substitution in the receptor binding domain of the spike glycoprotein.",,"['Navas-Martin, Sonia', 'Hingley, Susan T.', 'Weiss, Susan R.']",,,,
,PMC,Cytokine Responses in Severe Acute Respiratory Syndrome Coronavirus-Infected Macrophages In Vitro: Possible Relevance to Pathogenesis,http://dx.doi.org/10.1128/JVI.79.12.7819-7826.2005,PMC1143636,,,"The pathogenesis of severe acute respiratory syndrome (SARS) remains unclear. Macrophages are key sentinel cells in the respiratory system, and it is therefore relevant to compare the responses of human macrophages to infections with the SARS coronavirus (SARS-CoV) and other respiratory viruses. Primary human monocyte-derived macrophages were infected with SARS-CoV in vitro. Virus replication was monitored by measuring the levels of positive- and negative-strand RNA, by immunofluorescence detection of the SARS-CoV nucleoprotein, and by titration of the infectious virus. The gene expression profiles of macrophages infected with SARS-CoV, human coronavirus 229E, and influenza A (H1N1) virus were compared by using microarrays and real-time quantitative reverse transcriptase PCR. Secreted cytokines were measured with an enzyme-linked immunosorbent assay. SARS-CoV initiated viral gene transcription and protein synthesis in macrophages, but replication was abortive and no infectious virus was produced. In contrast to the case with human coronavirus 229E and influenza A virus, there was little or no induction of beta interferon (IFN-β) in SARS-CoV-infected macrophages. Furthermore, SARS-CoV induced the expression of chemokines such as CXCL10/IFN-γ-inducible protein 10 and CCL2/monocyte chemotactic protein 1. The poor induction of IFN-β, a key component of innate immunity, and the ability of the virus to induce chemokines could explain aspects of the pathogenesis of SARS.",,"['Cheung, Chung Y.', 'Poon, Leo L. M.', 'Ng, Iris H. Y.', 'Luk, Winsie', 'Sia, Sin-Fun', 'Wu, Mavis H. S.', 'Chan, Kwok-Hung', 'Yuen, Kwok-Yung', 'Gordon, Siamon', 'Guan, Yi', 'Peiris, Joseph S. M.']",,,,
,PMC,Characterization of the Tupaia Rhabdovirus Genome Reveals a Long Open Reading Frame Overlapping with P and a Novel Gene Encoding a Small Hydrophobic Protein,http://dx.doi.org/10.1128/JVI.79.11.6781-6790.2005,PMC1112159,,,"Rhabdoviruses are negative-stranded RNA viruses of the order Mononegavirales and have been isolated from vertebrates, insects, and plants. Members of the genus Lyssavirus cause the invariably fatal disease rabies, and a member of the genus Vesiculovirus, Chandipura virus, has recently been associated with acute encephalitis in children. We present here the complete genome sequence and transcription map of a rhabdovirus isolated from cultivated cells of hepatocellular carcinoma tissue from a moribund tree shrew. The negative-strand genome of tupaia rhabdovirus is composed of 11,440 nucleotides and encodes six genes that are separated by one or two intergenic nucleotides. In addition to the typical rhabdovirus genes in the order N-P-M-G-L, a gene encoding a small hydrophobic putative type I transmembrane protein of approximately 11 kDa was identified between the M and G genes, and the corresponding transcript was detected in infected cells. Similar to some Vesiculoviruses and many Paramyxovirinae, the P gene has a second overlapping reading frame that can be accessed by ribosomal choice and encodes a protein of 26 kDa, predicted to be the largest C protein of these virus families. Phylogenetic analyses of the tupaia rhabdovirus N and L genes show that the virus is distantly related to the Vesiculoviruses, Ephemeroviruses, and the recently characterized Flanders virus and Oita virus and further extends the sequence territory occupied by animal rhabdoviruses.",,"['Springfeld, Christoph', 'Darai, Gholamreza', 'Cattaneo, Roberto']",,,,
,PMC,Viral Expression of CCL2 Is Sufficient To Induce Demyelination in RAG1(−/−) Mice Infected with a Neurotropic Coronavirus,http://dx.doi.org/10.1128/JVI.79.11.7113-7120.2005,PMC1112157,,,"Mouse hepatitis virus strain JHM causes a chronic demyelinating disease in susceptible strains of rodents. Demyelination does not develop in infected RAG1(−/−) (recombination activation gene-deficient) mice but can be induced by several experimental interventions, including adoptive transfer of virus-specific T cells or antibodies. A common feature of demyelination in these models is extensive infiltration of macrophages/microglia into the white matter. The data obtained thus far do not indicate whether macrophage/microglia infiltration, in the absence of T cells or antibody, is sufficient to mediate demyelination. To determine whether the expression of a single macrophage chemoattractant, in the context of virus infection, could initiate the demyelinating process, we engineered a recombinant coronavirus that expressed the chemokine CCL2/monocyte chemoattractant protein-1. CCL2 has been implicated in macrophage infiltration into the central nervous system and is involved in demyelination in many experimental models of demyelination. Extensive macrophage/microglia infiltration and demyelination has developed in RAG1(−/−) mice infected with this recombinant virus. Thus, these results suggest that the minimal requirement for demyelination is increased expression of a single macrophage-attracting chemokine in the context of an inflammatory milieu, such as that induced by a viral infection.",,"['Kim, Taeg S.', 'Perlman, Stanley']",,,,
,PMC,Regulated and Liver-Specific Tamarin Alpha Interferon Gene Delivery by a Helper-Dependent Adenoviral Vector,http://dx.doi.org/10.1128/JVI.79.11.6772-6780.2005,PMC1112151,,,"Gene therapy approaches based on liver-restricted and regulated alpha interferon (IFN-α) expression, recently shown to be effective in different murine hepatitis models, appear promising alternatives to inhibit hepatitis C virus (HCV) replication in patients and minimize side effects. Tamarins (Saguinus species) infected by GB virus B (GBV-B) are considered a valid surrogate model for hepatitis C to study the biology of HCV infection and the development of new antiviral drugs. To test the efficacy of local delivery and expression of IFN-α in this model, we have developed HD-TET-tIFN, a helper-dependent adenovirus vector expressing tamarin IFN-α (tIFN) under the control of the tetracycline-inducible transactivator rtTA2(s)-S2. Expression of tIFN was successfully induced both in vitro and in vivo in rodents by doxycycline administration with consequent activation of IFN-responsive genes. More importantly, tIFN efficiently inhibited GBV-B replicon in a Huh-7 hepatoma cell line at low HD-TET-tIFN doses. A certain degree of transcriptional control of tIFN was achieved in tamarins injected with HD-TET-tIFN, but under the conditions used in this study, infection and replication of GBV-B were only delayed and not totally abrogated upon virus challenge. Hepatic delivery and regulated expression of IFN-α appear to be a possible approach for the cure of hepatitis, but this approach requires more studies to increase its efficacy. To our knowledge, this is the first report showing a regulated gene expression in a nonhuman primate hepatitis model.",,"['Aurisicchio, Luigi', 'De Tomassi, Amedeo', 'La Monica, Nicola', 'Ciliberto, Gennaro', 'Traboni, Cinzia', 'Palombo, Fabio']",,,,
,PMC,Selective Replication of Coronavirus Genomes That Express Nucleocapsid Protein,http://dx.doi.org/10.1128/JVI.79.11.6620-6630.2005,PMC1112145,,,"The coronavirus nucleocapsid (N) protein is a structural protein that forms a ribonucleoprotein complex with genomic RNA. In addition to its structural role, it has been described as an RNA-binding protein that might be involved in coronavirus RNA synthesis. Here, we report a reverse genetic approach to elucidate the role of N in coronavirus replication and transcription. We found that human coronavirus 229E (HCoV-229E) vector RNAs that lack the N gene were greatly impaired in their ability to replicate, whereas the transcription of subgenomic mRNA from these vectors was easily detectable. In contrast, vector RNAs encoding a functional N protein were able to carry out both replication and transcription. Furthermore, modification of the transcription signal required for the synthesis of N protein mRNAs in the HCoV-229E genome resulted in the selective replication of genomes that are able to express the N protein. This genetic evidence leads us to conclude that at least one coronavirus structural protein, the N protein, is involved in coronavirus replication.",,"['Schelle, Barbara', 'Karl, Nadja', 'Ludewig, Burkhard', 'Siddell, Stuart G.', 'Thiel, Volker']",,,,
,PMC,Identification and Characterization of the Putative Fusion Peptide of the Severe Acute Respiratory Syndrome-Associated Coronavirus Spike Protein,http://dx.doi.org/10.1128/JVI.79.11.7195-7206.2005,PMC1112137,,,"Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is a newly identified member of the family Coronaviridae and poses a serious public health threat. Recent studies indicated that the SARS-CoV viral spike glycoprotein is a class I viral fusion protein. A fusion peptide present at the N-terminal region of class I viral fusion proteins is believed to initiate viral and cell membrane interactions and subsequent fusion. Although the SARS-CoV fusion protein heptad repeats have been well characterized, the fusion peptide has yet to be identified. Based on the conserved features of known viral fusion peptides and using Wimley and White interfacial hydrophobicity plots, we have identified two putative fusion peptides (SARS(WW-I) and SARS(WW-II)) at the N terminus of the SARS-CoV S2 subunit. Both peptides are hydrophobic and rich in alanine, glycine, and/or phenylalanine residues and contain a canonical fusion tripeptide along with a central proline residue. Only the SARS(WW-I) peptide strongly partitioned into the membranes of large unilamellar vesicles (LUV), adopting a β-sheet structure. Likewise, only SARS(WW-I) induced the fusion of LUV and caused membrane leakage of vesicle contents at peptide/lipid ratios of 1:50 and 1:100, respectively. The activity of this synthetic peptide appeared to be dependent on its amino acid (aa) sequence, as scrambling the peptide rendered it unable to partition into LUV, assume a defined secondary structure, or induce both fusion and leakage of LUV. Based on the activity of SARS(WW-I), we propose that the hydrophobic stretch of 19 aa corresponding to residues 770 to 788 is a fusion peptide of the SARS-CoV S2 subunit.",,"['Sainz, Bruno', 'Rausch, Joshua M.', 'Gallaher, William R.', 'Garry, Robert F.', 'Wimley, William C.']",,,,
,PMC,Cinanserin Is an Inhibitor of the 3C-Like Proteinase of Severe Acute Respiratory Syndrome Coronavirus and Strongly Reduces Virus Replication In Vitro,http://dx.doi.org/10.1128/JVI.79.11.7095-7103.2005,PMC1112131,,,"The 3C-like proteinase (3CL(pro)) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one of the most promising targets for anti-SARS-CoV drugs due to its crucial role in the viral life cycle. In this study, a database containing structural information of more than 8,000 existing drugs was virtually screened by a docking approach to identify potential binding molecules of SARS-CoV 3CL(pro). As a target for screening, both a homology model and the crystallographic structure of the binding pocket of the enzyme were used. Cinanserin (SQ 10,643), a well-characterized serotonin antagonist that has undergone preliminary clinical testing in humans in the 1960s, showed a high score in the screening and was chosen for further experimental evaluation. Binding of both cinanserin and its hydrochloride to bacterially expressed 3CL(pro) of SARS-CoV and the related human coronavirus 229E (HCoV-229E) was demonstrated by surface plasmon resonance technology. The catalytic activity of both enzymes was inhibited with 50% inhibitory concentration (IC(50)) values of 5 μM, as tested with a fluorogenic substrate. The antiviral activity of cinanserin was further evaluated in tissue culture assays, namely, a replicon system based on HCoV-229E and quantitative test assays with infectious SARS-CoV and HCoV-229E. All assays revealed a strong inhibition of coronavirus replication at nontoxic drug concentrations. The level of virus RNA and infectious particles was reduced by up to 4 log units, with IC(50) values ranging from 19 to 34 μM. These findings demonstrate that the old drug cinanserin is an inhibitor of SARS-CoV replication, acting most likely via inhibition of the 3CL proteinase.",,"['Chen, Lili', 'Gui, Chunshan', 'Luo, Xiaomin', 'Yang, Qingang', 'Günther, Stephan', 'Scandella, Elke', 'Drosten, Christian', 'Bai, Donglu', 'He, Xichang', 'Ludewig, Burkhard', 'Chen, Jing', 'Luo, Haibin', 'Yang, Yiming', 'Yang, Yifu', 'Zou, Jianping', 'Thiel, Volker', 'Chen, Kaixian', 'Shen, Jianhua', 'Shen, Xu', 'Jiang, Hualiang']",,,,
,PMC,Articles of Significant Interest Selected from This Issue by the Editors,http://dx.doi.org/10.1128/JVI.79.11.6575-6576.2005,PMC1112094,,,,,,,,,
,PMC,Pulmonary artery thrombosis in a patient with severe acute respiratory syndrome,http://dx.doi.org/10.1136/pgmj.2004.030049,PMC1743280,,,"Severe acute respiratory syndrome (SARS) is an emerging infectious disease with both pulmonary and extra-pulmonary manifestations. Although coagulation abnormalities are common in these patients, clinically overt thromboembolic events are rarely reported. This report describes the first case of pulmonary artery thrombosis in a patient with laboratory confirmed SARS.",,"['Ng, K', 'Wu, A', 'Cheng, V', 'Tang, B', 'Chan, C', 'Yung, C', 'Luk, S', 'Lee, T', 'Chow, L', 'Yuen, K']",,,,
,PMC,Smoking attributable mortality for Taiwan and its projection to 2020 under different smoking scenarios,http://dx.doi.org/10.1136/tc.2004.007955,PMC1766186,,,"Objectives: To estimate smoking attributable mortality (SAM) in Taiwan for the years 2001 through 2020 under scenarios of reductions in smoking rates by 0%, 2%, 4%, and 10% per year. Method: The smoking attributable fraction (SAF) was used to calculate SAM from the risk experience in following up a large cohort (86 580 people) in Taiwan. Smoking rates were based on the 2001 National Health Interview Survey and other national surveys. An average 10 year lag was assumed between smoking rates and subsequent mortality. Results: In 2001, 18 803 deaths, or 1 out of 4 deaths (27%), in middle aged men (35–69 years old) were attributable to smoking. SAM has been increasing and will continue to increase if smoking rates remain constant or even if reduced annually by 2%. SAM would begin to decrease only if rates were to be reduced by at least 4% a year. Conclusions: The projected SAM in this study illustrates the seriousness of smoking caused mortality. Current efforts in tobacco control would lead to a progressive increase in SAM, unless efforts were doubled and smoking rates reduced by more than 4% a year. The urgency in requiring stronger tobacco control programmes to attenuate the staggering death tolls is compelling.",,"['Wen, C', 'Tsai, S', 'Chen, C', 'Cheng, T', 'Tsai, M', 'Levy, D']",,,,
,PMC,Reducing health disparity in Taiwan: quantifying the role of smoking,http://dx.doi.org/10.1136/tc.2003.005546,PMC1766179,,,"Objective: To assess the impact of smoking disparities on health disparities, in terms of gap in life expectancy, in Taiwan cities and counties. Methods: Using the decomposition method of life expectancy, the contribution of each disease category to the life expectancy gap was quantitatively expressed as the number of years of life. The smoking attributable fraction (SAF) was calculated for each city and county based on their respective smoking prevalence and relative risk for each smoking related disease. The smoking attributable gap (SAG) in life expectancy between two sites is the sum of the difference in SAF between two sites for each smoking related disease multiplied by the number of years this disease contributed to the life expectancy gap. Results: Significant health and smoking disparities were present among the 23 cities and counties in Taiwan. These health disparities and smoking disparities were highly correlated (R(2) = 0.3676). Generally, the health gap increased with increasing smoking disparity. The disparity in smoking prevalence and intensity among cities and counties in Taiwan was responsible for up to 19% of the health disparity. The health disparity is also highly correlated (R(2) = 0.3745) with SAG in life expectancy. Conclusions: Reducing smoking is important to health, and reducing the smoking disparity is also important for reducing the health disparity observed in Taiwan. The larger the health disparity is, the more important the smoking attributable disparity could be. The reduction of smoking disparities could be a realistic and cost effective way toward reducing health disparities.",,"['Cheng, T', 'Wen, C', 'Tsai, S', 'Chung, W', 'Hsu, C']",,,,
,PMC,Humanized mice develop coronavirus respiratory disease,http://dx.doi.org/10.1073/pnas.0503091102,PMC1149438,,,,,"['Baric, Ralph S.', 'Sims, Amy C.']",,,,
,PMC,Health assembly adopts new regulations for tackling emergencies,,PMC558127,,,,,"Ress, Paul",,,,
,PMC,Development of a transgenic mouse model susceptible to human coronavirus 229E,http://dx.doi.org/10.1073/pnas.0408589102,PMC1140478,,,"Human coronavirus (HCoV) 229E is a group 1 coronavirus and is specific to humans. So far, no animal model is available to study the pathogenesis of infection by HCoV-229E. We show here that the expression of aminopeptidase N (APN, also termed CD13), the receptor for HCoV-229E, is required but not sufficient to confer susceptibility in vivo. HCoV-229E infection was facilitated by crossing APN transgenic mice into signal transducers and activators of transcription (Stat) 1 null mice and by adaptation of HCoV-229E to grow in primary APN transgenic, Stat1 null fibroblasts. Double transgenic mice allow the study of human coronavirus group 1 infections in an animal model, in particular, viral tropism, replication, recombination, and spread in an immunocompromised situation. Furthermore, these mice provide an important tool for the evaluation of biosafety and efficacy of coronavirus-based vectors.",,"['Lassnig, Caroline', 'Sanchez, Carlos M.', 'Egerbacher, Monika', 'Walter, Ingrid', 'Majer, Susanne', 'Kolbe, Thomas', 'Pallares, Pilar', 'Enjuanes, Luis', 'Müller, Mathias']",,,,
,PMC,TEB4 is a C4HC3 RING finger-containing ubiquitin ligase of the endoplasmic reticulum,http://dx.doi.org/10.1042/BJ20041241,PMC1138973,,,"In the present study, the human TEB4 is identified as a novel ER (endoplasmic reticulum)-resident ubiquitin ligase. TEB4 has homologues in many species and has a number of remarkable properties. TEB4 contains a conserved RING (really interesting new gene) finger and 13 predicted transmembrane domains. The RING finger of TEB4 and its homologues is situated at the N-terminus and has the unconventional C4HC3 configuration. The N-terminus of TEB4 is located in the cytosol. We show that the isolated TEB4 RING domain catalyses ubiquitin ligation in vitro in a reaction that is ubiquitin Lys(48)-specific and involves UBC7 (ubiquitin-conjugating enzyme 7). These properties are reminiscent of E3 enzymes, which are involved in ER-associated protein degradation. TEB4 is an ER degradation substrate itself, promoting its own degradation in a RING finger- and proteasome-dependent manner.",,"['Hassink, Gerco', 'Kikkert, Marjolein', 'Voorden, Sjaak\xa0van', 'Lee, Shiow-Ju', 'Spaapen, Robbert', 'Laar, Theo\xa0van', 'Coleman, Catherine\xa0S.', 'Bartee, Eric', 'Früh, Klaus', 'Chau, Vincent', 'Wiertz, Emmanuel']",,,,
,PMC,"The worldwide air transportation network: Anomalous centrality, community structure, and cities' global roles",http://dx.doi.org/10.1073/pnas.0407994102,PMC1142352,,,"We analyze the global structure of the worldwide air transportation network, a critical infrastructure with an enormous impact on local, national, and international economies. We find that the worldwide air transportation network is a scale-free small-world network. In contrast to the prediction of scale-free network models, however, we find that the most connected cities are not necessarily the most central, resulting in anomalous values of the centrality. We demonstrate that these anomalies arise because of the multicommunity structure of the network. We identify the communities in the air transportation network and show that the community structure cannot be explained solely based on geographical constraints and that geopolitical considerations have to be taken into account. We identify each city's global role based on its pattern of intercommunity and intracommunity connections, which enables us to obtain scale-specific representations of the network.",,"['Guimerà, R.', 'Mossa, S.', 'Turtschi, A.', 'Amaral, L. A. N.']",,,,
,PMC,Clinical features of probable severe acute respiratory syndrome in Beijing,http://dx.doi.org/10.3748/wjg.v11.i19.2971,PMC4305670,,,"AIM: To summarize clinical features of probable severe acute respiratory syndrome (SARS) in Beijing. METHODS: Retrospective cases involving 801 patients admitted to hospitals in Beijing between March and June 2003, with a diagnosis of probable SARS, moderate type. The series of clinical manifestation, laboratory and radiograph data obtained from 801 cases were analyzed. RESULTS: One to three days after the onset of SARS, the major clinical symptoms were fever (in 88.14% of patients), fatigue, headache, myalgia, arthralgia (25-36%), etc. The counts of WBC (in 22.56% of patients) lymphocyte (70.25%) and CD3, CD4, CD8 positive T cells (70%) decreased. From 4-7 d, the unspecific symptoms became weak; however, the rates of low respiratory tract symptoms, such as cough (24.18%), sputum production (14.26%), chest distress (21.04%) and shortness of breath (9.23%) increased, so did the abnormal rates on chest radiograph or CT. The low counts of WBC, lymphocyte and CD3, CD4, CD8 positive T cells touched bottom. From 8 to 16 d, the patients presented progressive cough (29.96%), sputum production (13.09%), chest distress (29.96%) and shortness of breath (35.34%). All patients had infiltrates on chest radiograph or CT, some even with multi-infiltrates. Two weeks later, patients’ respiratory symptoms started to alleviate, the infiltrates on the lung began to absorb gradually, the counts of WBC, lymphocyte and CD3, CD4, CD8 positive T cells were restored to normality. CONCLUSION: The data reported here provide evidence that the course of SARS could be divided into four stages, namely the initial stage, progressive stage, fastigium and convalescent stage.",,"['Lu, Hai-Ying', 'Xu, Xiao-Yuan', 'Lei, Yu', 'Wu, Yang-Feng', 'Chen, Bo-Wen', 'Xiao, Feng', 'Xie, Gao-Qiang', 'Han, De-Min']",,,,
,PMC,International Electives: Maximizing the Opportunity to Learn and Contribute,,PMC1681550,,,,,"['Gupta, Rajesh', 'Farmer, Paul E.']",,,,
,PMC,Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry,http://dx.doi.org/10.1073/pnas.0409465102,PMC1142358,,,"Coronavirus (CoV) infection of humans is usually not associated with severe disease. However, discovery of the severe acute respiratory syndrome (SARS) CoV revealed that highly pathogenic human CoVs (HCoVs) can evolve. The identification and characterization of new HCoVs is, therefore, an important task. Recently, a HCoV termed NL63 was discovered in patients with respiratory tract illness. Here, cell tropism and receptor usage of HCoV-NL63 were analyzed. The NL63 spike (S) protein mediated infection of different target cells compared with the closely related 229E-S protein but facilitated entry into cells known to be permissive to SARS-CoV-S-driven infection. An analysis of receptor engagement revealed that NL63-S binds angiotensin-converting enzyme (ACE) 2, the receptor for SARS-CoV, and HCoV-NL63 uses ACE2 as a receptor for infection of target cells. Potent neutralizing activity directed against NL63- but not 229E-S protein was detected in virtually all sera from patients 8 years of age or older, suggesting that HCoV-NL63 infection of humans is common and usually acquired during childhood. Here, we show that SARS-CoV shares its receptor ACE2 with HCoV-NL63. Because the two viruses differ dramatically in their ability to induce disease, analysis of HCoV-NL63 might unravel pathogenicity factors in SARS-CoV. The frequent HCoV-NL63 infection of humans suggests that highly pathogenic variants have ample opportunity to evolve, underlining the need for vaccines against HCoVs.",,"['Hofmann, Heike', 'Pyrc, Krzysztof', 'van der Hoek, Lia', 'Geier, Martina', 'Berkhout, Ben', 'Pöhlmann, Stefan']",,,,
,PMC,Yeast genome-wide screen reveals dissimilar sets of host genes affecting replication of RNA viruses,http://dx.doi.org/10.1073/pnas.0502604102,PMC1129141,,,"Viruses are devastating pathogens of humans, animals, and plants. To further our understanding of how viruses use the resources of infected cells, we systematically tested the yeast single-gene-knockout library for the effect of each host gene on the replication of tomato bushy stunt virus (TBSV), a positive-strand RNA virus of plants. The genome-wide screen identified 96 host genes whose absence either reduced or increased the accumulation of the TBSV replicon. The identified genes are involved in the metabolism of nucleic acids, lipids, proteins, and other compounds and in protein targeting/transport. Comparison with published genome-wide screens reveals that the replication of TBSV and brome mosaic virus (BMV), which belongs to a different supergroup among plus-strand RNA viruses, is affected by vastly different yeast genes. Moreover, a set of yeast genes involved in vacuolar targeting of proteins and vesicle-mediated transport both affected replication of the TBSV replicon and enhanced the cytotoxicity of the Parkinson's disease-related α-synuclein when this protein was expressed in yeast. In addition, a set of host genes involved in ubiquitin-dependent protein catabolism affected both TBSV replication and the cytotoxicity of a mutant huntingtin protein, a candidate agent in Huntington's disease. This finding suggests that virus infection and disease-causing proteins might use or alter similar host pathways and may suggest connections between chronic diseases and prior virus infection.",,"['Panavas, Tadas', 'Serviene, Elena', 'Brasher, Jeremy', 'Nagy, Peter D.']",,,,
,PMC,Cytokine Profiles in Human Immunodeficiency Virus-Infected Children Treated With Highly Active Antiretroviral Therapy,,PMC1681548,,,"ABSTRACT: CONTEXT: There have been few longitudinal studies of cytokine production in neonatally acquired HIV-1 infection and none in Asian or Chinese children. OBJECTIVE: To determine whether monitoring cytokine production could contribute to the better management of pediatric patients with HIV-1 infection. SETTING: Clinical Immunology Laboratory and Pediatrics Department, University Hospital, Hong Kong. PATIENTS: Ten Asian and 2 Eurasian children infected with HIV-1 by mother-to-child transmission were followed for up to 5 years while on treatment with highly active antiretroviral therapy (HAART). MAIN OUTCOME MEASURES: Numbers of unstimulated and mitogen-activated cytokine-secreting cells (IFN-gamma, interleukin [IL]-2, IL-4, IL-6, IL-10, IL-12, and TNF-alpha) were measured by ELISPOT assay at frequent intervals, and correlations were sought with CD4+ and CD8+ cell counts and viral loads. RESULTS: Mitogen-stimulated IL-2-secreting cells were directly associated with recovery of CD4+ cells. Correlations with viral load were found for Con A-induced IFN-gamma, Con A-induced IL-4, and unstimulated IL-10, suggesting that these cytokines were either suppressed by high virus levels or that higher cytokine levels suppressed virus. IFN-gamma, IL-2-, IL-4-, and IL-12-secreting cells induced by PHA, Con A, and/or SAC tended to increase for the first 3–4 years of treatment but declined thereafter. CONCLUSIONS: Alterations in cytokine profiles were not associated with adverse clinical events and there was little evidence to indicate that monitoring cytokine enzyme-linked immunospots (ELISPOTs) could contribute to pediatric patient management. INTRODUCTION: With the advent of highly active antiretroviral therapy (HAART), human immunodeficiency virus type 1 (HIV-1) can be controlled for prolonged periods,[1] although the virus cannot be eliminated[2] and treatment failures occur due to development of drug-resistant mutations.[3] Chronic immune hyperactivation and raised T-cell turnover due to continued viral replication and antigenic stimulation are present even after HAART has decreased the viral load to undetectable levels.[4] Both proinflammatory and regulatory cytokines are produced during chronic immune stimulation. Proinflammatory cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-alpha), contribute to tissue pathology, especially in the brain,[5] and can induce transcription of latent HIV-1.[6,7] Type 2 or regulatory cytokines, such as IL-4, IL-6, and IL-10, can suppress type 1 cytokines and induce polyclonal B-cell activation,[8] lymphomagenesis,[9] autoantibody production,[10] and manifestations of allergy.[11] Type 1 cytokines, such as IL-12, interferon (IFN) gamma, and IL-2, are important for antiviral cell-mediated immunity.[12] During the long course of HIV-1 infection, type 2 cytokines gradually come to predominate over type 1 cytokines,[13–16] although this finding is not universally accepted.[17] There have been few studies of in vitro cytokine production in neonatally acquired HIV-1 infection in Asian or Chinese children. The enzyme-linked immunospot (ELISPOT) system for measuring unstimulated or mitogen-activated cytokine secreting cells has not been evaluated in this context. We wished to know whether monitoring cytokine production in addition to CD4+ cell counts and viral load could provide additional useful information in pediatric patients with HIV-1 infection being treated with HAART. We hoped to identify cytokine profiles that are characteristic of either clinical improvement or disease progression, so that manipulation towards the desirable profile might be attempted.",,"['Jones, Brian M.', 'Chiu, Susan S.S.', 'Wong, Wilfred H.S.', 'Lim, Wilina W.L.', 'Lau, Yu-lung']",,,,
,PMC,Evaluating the Safety of New Vaccines: Summary of a Workshop,http://dx.doi.org/10.2105/AJPH.2004.039438,PMC1449258,,,"Public concerns about the safety of vaccines arise on a regular basis. In November 2000, a workshop titled “Evaluation of New Vaccines: How Much Safety Data?” was convened by US Public Health Service agencies, including the Food and Drug Administration, the National Institutes of Health, the Centers for Disease Control and Prevention, and the Health Resources and Services Administration, to discuss appropriate methods for evaluating the safety of new vaccines. Workshop presentations addressed the current standards and approaches for new vaccine evaluation and postlicensure surveillance, as well as public views about vaccine safety and alternative approaches that could be considered. The advantages and disadvantages of conducting large controlled trials before licensure or widespread use of a new vaccine were discussed. We summarize these presentations and discussions.",,"['Ellenberg, Susan S.', 'Foulkes, Mary A.', 'Midthun, Karen', 'Goldenthal, Karen L.']",,,,
,PMC,Detection of coronavirus in cases of tracheobronchitis in dogs: a retrospective study from 1971 to 2003.,,PMC2831589,,,,,"['Ellis, John A.', 'McLean, Nikki', 'Hupaelo, Richard', 'Haines, Deborah M.']",,,,
,PMC,Blind omphalitis and palatine abscess in a bull calf,,PMC1090452,,,"Neurological, respiratory, and gastrointestinal signs in a 2-month-old veal calf were suggestive of a possible herd problem. Autopsy revealed an umbilical abscess, an abscess on the soft palate, and mild chronic enteritis and pulmonary edema. Virologic and bacteriologic investigations did not provide a definitive diagnosis.",,"Dittenhoffer, Christian",,,,
,PMC,The effect of treatment duration on weaning weights in a cow-calf herd with a protracted severe outbreak of diarrhea in calves,,PMC1090447,,,"The objective of this study was to describe a multiyear outbreak of calf diarrhea in an Alberta cow-calf herd and the impact of severe diarrhea on calf productivity. A retrospective analysis was performed through the use of detailed individual animal records and laboratory reports. The most significant laboratory finding was Salmonella Typhimurium isolated from the fecal samples of 2 ill members of the treatment crew and from 3 calves on postmortem examination. In 2002, at the peak of the outbreak, 90.3% (325/360) of the calves required treatment and 8.9% (32/360) of the calves died. In 2003, the severity of the problem had declined with only 20.9% (47/225) of the calves requiring treatment and 3.1% (7/225) of the calves dying. In both years, the weaning weights of treated calves were significantly reduced compared with those of nontreated calves. For calves weaned in 2002, after adjusting for the effect of calf sex, calves treated more than 6 times had 200-day adjusted weaning weights that were 15.2 kg (95% CI; 5.8 to 24.4 kg) lighter than of those calves treated only once or not at all (P = 0.0015, n = 321). For calves weaned in 2003, calves were 5.5 kg (95% CI; 0.23 to 10.8, P = 0.04, n = 207) lighter per treatment day with electrolytes, when calf sex and dam age were controlled for. Assuming that increased days of treatment or number of treatments is representative of disease severity, long-term calf performance is negatively affected by severe calfhood disease. The estimated lost revenue and treatment expenses, excluding the cost of labor, cow feed, and maintenance, was $22 800 in 2002 and $1589 in 2003.",,"['Gow, Sheryl', 'Waldner, Cheryl', 'Ross, Carol']",,,,
,PMC,Human Metapneumovirus: An Important Cause of Respiratory Disease in Children and Adults,,PMC3347970,,,"Human metapneumovirus is a paramyxovirus that was discovered in 2001 in the Netherlands. Epidemiologic studies have shown it to be a major cause of acute respiratory tract disease in normal infants and children worldwide, with a seasonal occurrence and spectrum of clinical illness most similar to the closely related respiratory syncytial virus. The greatest prevalence of severe disease requiring hospitalization in otherwise healthy children appears to be in those aged between 6 and 12 months, older than the peak age of hospitalizations for respiratory syncytial virus. Human metapneumovirus is also a significant cause of acute respiratory disease in adults, particularly the elderly and those with comorbid conditions such as chronic obstructive pulmonary disease, asthma, and cancer. Because there is no rapid diagnostic assay, reverse transcriptase polymerase chain reaction is most widely used. Animal models have been developed, and candidate live-attenuated vaccines are in preclinical trials, offering the potential for future interventions in high-risk groups.",,"Williams, John V.",,,,
,PMC,"Dengue Fever, Hawaii, 2001–2002",http://dx.doi.org/10.3201/eid1105.041063,PMC3320380,15890132,NO-CC CODE,"Autochthonous dengue infections were last reported in Hawaii in 1944. In September 2001, the Hawaii Department of Health was notified of an unusual febrile illness in a resident with no travel history; dengue fever was confirmed. During the investigation, 1,644 persons with locally acquired denguelike illness were evaluated, and 122 (7%) laboratory-positive dengue infections were identified; dengue virus serotype 1 was isolated from 15 patients. No cases of dengue hemorrhagic fever or shock syndrome were reported. In 3 instances autochthonous infections were linked to a person who reported denguelike illness after travel to French Polynesia. Phylogenetic analyses showed the Hawaiian isolates were closely associated with contemporaneous isolates from Tahiti. Aedes albopictus was present in all communities surveyed on Oahu, Maui, Molokai, and Kauai; no Ae. aegypti were found. This outbreak underscores the importance of maintaining surveillance and control of potential disease vectors even in the absence of an imminent disease threat.",2005 May,"['Effler, Paul V.', 'Pang, Lorrin', 'Kitsutani, Paul', 'Vorndam, Vance', 'Nakata, Michele', 'Ayers, Tracy', 'Elm, Joe', 'Tom, Tammy', 'Reiter, Paul', 'Rigau-Perez, José G.', 'Hayes, John M.', 'Mills, Kristin', 'Napier, Mike', 'Clark, Gary G.', 'Gubler, Duane J.', None]",Emerg Infect Dis,,,
,PMC,Rapid and Sensitive Detection of Severe Acute Respiratory Syndrome Coronavirus by Rolling Circle Amplification,http://dx.doi.org/10.1128/JCM.43.5.2339-2344.2005,PMC1153787,,,"The severe acute respiratory syndrome (SARS) epidemic of 2003 was responsible for 774 deaths and caused significant economic damage worldwide. Since July 2003, a number of SARS cases have occurred in China, raising the possibility of future epidemics. We describe here a rapid, sensitive, and highly efficient assay for the detection of SARS coronavirus (SARS-CoV) in cultured material and a small number (n = 7) of clinical samples. Using rolling circle amplification (RCA), we were able to achieve sensitive detection levels of SARS-CoV RNA in both solid and liquid phases. The main advantage of RCA is that it can be performed under isothermal conditions with minimal reagents and avoids the generation of false-positive results, a problem that is frequently encountered in PCR-based assays. Furthermore, the RCA technology provides a faster, more sensitive, and economical option to currently available PCR-based methods.",,"['Wang, Bin', 'Potter, Simon J.', 'Lin, Yiguang', 'Cunningham, Anthony L.', 'Dwyer, Dominic E.', 'Su, Yuelong', 'Ma, Xuejun', 'Hou, Yunde', 'Saksena, Nitin K.']",,,,
,PMC,Development and Evaluation of a Multitarget Real-Time Taqman Reverse Transcription-PCR Assay for Detection of the Severe Acute Respiratory Syndrome-Associated Coronavirus and Surveillance for an Apparently Related Coronavirus Found in Masked Palm Civets,http://dx.doi.org/10.1128/JCM.43.5.2041-2046.2005,PMC1153763,,,"Severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) is the etiological agent of SARS. It is believed that SARS-CoV originates from wild animals. We have developed a multitarget real-time Taqman reverse transcription-PCR (RT-PCR) assay for the quantitative detection of SARS-CoV. The sequences of the Taqman probes with a minor groove binder and the corresponding primers were based on the sequences of the N gene, open reading frame (ORF) 3, and ORF 8. The overall linear range of this assay was from at least 10(1) to 10(6) copies per reaction, and the detection limit could reach less than 10 copies per reaction. The quantification results for SARS-CoV from cell culture correlated well with those of the RT-PCR by using any two of the three sets of primer and probe used in this assay. However, the results of quantification of SARS-CoV obtained by using a few available throat swab specimens from SARS patients and the N gene as the target were almost 10 times higher than those obtained by using ORF 3 and ORF 8. Using this assay, we also detected an apparently SARS-CoV-related coronavirus in the throat swab specimens from masked palm civets in the west part of Hubei Province, People's Republic of China.",,"['Hu, Wenqian', 'Bai, Bingke', 'Hu, Zhihong', 'Chen, Ze', 'An, Xuefang', 'Tang, Lijun', 'Yang, Jihong', 'Wang, Hualin', 'Wang, Hanzhong']",,,,
,PMC,Immunofluorescence Assay for Detection of the Nucleocapsid Antigen of the Severe Acute Respiratory Syndrome (SARS)-Associated Coronavirus in Cells Derived from Throat Wash Samples of Patients with SARS,http://dx.doi.org/10.1128/JCM.43.5.2444-2448.2005,PMC1153760,,,"An antigen detection assay for severe acute respiratory syndrome (SARS) coronavirus was established in this study by an indirect immunofluorescence test, which utilized cells derived from throat wash samples of patients with SARS and a rabbit serum that recognized the nucleocapsid protein of SARS-associated coronavirus (SARS-CoV) but not that of other human coronavirus tested. It detected SARS-CoV in 11 of 17 (65%) samples from SARS patients as early as day 2 of illness but in none of the 10 samples from healthy controls. Compared with other diagnostic modalities for detecting SARS-CoV, this assay is simpler, more convenient, and economical. It could be an alternative for early and rapid diagnosis, should SARS return in the future.",,"['Liu, I-Jung', 'Chen, Pei-Jer', 'Yeh, Shiou-Hwei', 'Chiang, Yu-Ping', 'Huang, Li-Min', 'Chang, Ming-Fu', 'Chen, Shey-Ying', 'Yang, Pan-Chyr', 'Chang, Shan-Chwen', 'Wang, Wei-Kung', None]",,,,
,PMC,Medical Education and JGIM,http://dx.doi.org/10.1111/j.1525-1497.2005.41009.x,PMC1490124,,,,,"['Williams, Brent C', 'Gerrity, Martha S']",,,,
,PMC,The Impact of Severe Acute Respiratory Syndrome on Medical House Staff: A Qualitative Study,http://dx.doi.org/10.1111/j.1525-1497.2005.0099.x,PMC1490116,,,"OBJECTIVE: To explore the impact of severe acute respiratory syndrome (SARS) on a medical training program and to develop principles for professional training programs to consider in dealing with future, similar crises. DESIGN: Qualitative interviews analyzed using grounded theory methodology. SETTING: University-affiliated hospitals in Toronto, Canada during the SARS outbreak in 2003. PARTICIPANTS: Medical house staff who were allocated to a general internal medicine clinical teaching unit, infectious diseases consultation service, or intensive care unit. RESULTS: Seventeen medical residents participated in this study. Participants described their experiences during the outbreak and highlighted several themes including concerns about their personal safety and about the negative impact of the outbreak on patient care, house staff education, and their emotional well-being. CONCLUSION: The ability of residents to cope with the stress of the SARS outbreak was enhanced by the communication of relevant information and by the leadership of their supervisors and infection control officers. It is hoped that training programs for health care professionals will be able to implement these tenets of crisis management as they develop strategies for dealing with future health threats.",,"['Rambaldini, Gloria', 'Wilson, Kumanan', 'Rath, Darlyne', 'Lin, Yulia', 'Gold, Wayne L', 'Kapral, Moira K', 'Straus, Sharon E']",,,,
,PMC,A single immunization with a rhabdovirus-based vector expressing severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high levels of SARS-CoV-neutralizing antibodies,http://dx.doi.org/10.1099/vir.0.80844-0,PMC1361274,,,"Foreign viral proteins expressed by rabies virus (RV) have been shown to induce potent humoral and cellular immune responses in immunized animals. In addition, highly attenuated and, therefore, very safe RV-based vectors have been constructed. Here, an RV-based vaccine vehicle was utilized as a novel vaccine against severe acute respiratory syndrome coronavirus (SARS-CoV). For this approach, the SARS-CoV nucleocapsid protein (N) or envelope spike protein (S) genes were cloned between the RV glycoprotein G and polymerase L genes. Recombinant vectors expressing SARS-CoV N or S protein were recovered and their immunogenicity was studied in mice. A single inoculation with the RV-based vaccine expressing SARS-CoV S protein induced a strong SARS-CoV-neutralizing antibody response. The ability of the RV-SARS-CoV S vector to confer immunity after a single inoculation makes this live vaccine a promising candidate for eradication of SARS-CoV in animal reservoirs, thereby reducing the risk of transmitting the infection to humans.",,"['Faber, Milosz', 'Lamirande, Elaine W.', 'Roberts, Anjeanette', 'Rice, Amy B.', 'Koprowski, Hilary', 'Dietzschold, Bernhard', 'Schnell, Matthias J.']",,,,
,PMC,Infectious Bronchitis Virus 3a Protein Localizes to a Novel Domain of the Smooth Endoplasmic Reticulum,http://dx.doi.org/10.1128/JVI.79.10.6142-6151.2005,PMC1091725,,,"All coronaviruses possess small open reading frames (ORFs) between structural genes that have been hypothesized to play important roles in pathogenesis. Infectious bronchitis virus (IBV) ORF 3a is one such gene. It is highly conserved among group 3 coronaviruses, suggesting that it has an important function in infection. IBV 3a protein is expressed in infected cells but is not detected in virions. Sequence analysis predicted that IBV 3a was a membrane protein; however, only a fraction behaved like an integral membrane protein. Microscopy and immunoprecipitation studies demonstrated that IBV 3a localized to the cytoplasm in a diffuse pattern as well as in sharp puncta in both infected and transfected cells. These puncta did not overlap cellular organelles or other punctate structures. Confocal microscopy demonstrated that IBV 3a puncta lined up along smooth endoplasmic reticulum (ER) tubules and, in a significant number of instances, were partially surrounded by these tubules. Our results suggest that IBV 3a is partially targeted to a novel domain of the smooth ER.",,"['Pendleton, Amanda R.', 'Machamer, Carolyn E.']",,,,
,PMC,Comparative Host Gene Transcription by Microarray Analysis Early after Infection of the Huh7 Cell Line by Severe Acute Respiratory Syndrome Coronavirus and Human Coronavirus 229E,http://dx.doi.org/10.1128/JVI.79.10.6180-6193.2005,PMC1091719,,,"The pathogenesis of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) at the cellular level is unclear. No human cell line was previously known to be susceptible to both SARS-CoV and other human coronaviruses. Huh7 cells were found to be susceptible to both SARS-CoV, associated with SARS, and human coronavirus 229E (HCoV-229E), usually associated with the common cold. Highly lytic and productive rates of infections within 48 h of inoculation were reproducible with both viruses. The early transcriptional profiles of host cell response to both types of infection at 2 and 4 h postinoculation were determined by using the Affymetrix HG-U133A microarray (about 22,000 genes). Much more perturbation of cellular gene transcription was observed after infection by SARS-CoV than after infection by HCoV-229E. Besides the upregulation of genes associated with apoptosis, which was exactly opposite to the previously reported effect of SARS-CoV in a colonic carcinoma cell line, genes related to inflammation, stress response, and procoagulation were also upregulated. These findings were confirmed by semiquantitative reverse transcription-PCR, reverse transcription-quantitative PCR for mRNA of genes, and immunoassays for some encoded proteins. These transcriptomal changes are compatible with the histological changes of pulmonary vasculitis and microvascular thrombosis in addition to the diffuse alveolar damage involving the pneumocytes.",,"['Tang, Bone S. F.', 'Chan, Kwok-hung', 'Cheng, Vincent C. C.', 'Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Lam, Clarence C. K.', 'Chan, Tsun-leung', 'Wu, Alan K. L.', 'Hung, Ivan F. N.', 'Leung, Suet-yi', 'Yuen, Kwok-yung']",,,,
,PMC,Receptor-Independent Spread of a Highly Neurotropic Murine Coronavirus JHMV Strain from Initially Infected Microglial Cells in Mixed Neural Cultures,http://dx.doi.org/10.1128/JVI.79.10.6102-6110.2005,PMC1091713,,,"Although neurovirulent mouse hepatitis virus (MHV) strain JHMV multiplies in a variety of brain cells, expression of its receptor carcinoembryonic antigen cell adhesion molecule 1 (CEACAM 1) (MHVR) is restricted only in microglia. The present study was undertaken to clarify the mechanism of an extensive JHMV infection in the brain by using neural cells isolated from mouse brain. In contrast to wild-type (wt) JHMV, a soluble-receptor-resistant mutant (srr7) infects and spreads solely in an MHVR-dependent fashion (F. Taguchi and S. Matsuyama, J. Virol. 76:950-958, 2002). In mixed neural cell cultures, srr7 infected a limited number of cells and infection did not spread, although wt JHMV induced syncytia in most of the cells. srr7-infected cells were positive for GS-lectin, a microglia marker. Fluorescence-activated cell sorter analysis showed that about 80% of the brain cells stained with anti-MHVR antibody (CC1) were also positive for GS-lectin. Pretreatment of those cells with CC1 prevented virus attachment to the cell surface and also blocked virus infection. These results show that microglia express functional MHVR that mediates JHMV infection. As expected, in microglial cell-enriched cultures, both srr7and wt JHMV produced syncytia in a majority of cells. Treatment with CC1 of mixed neural cell cultures and microglia cultures previously infected with wt virus failed to block the spread of infection, indicating that wt infection spreads in an MHVR-independent fashion. Thus, the present study indicates that microglial cells are the major population of the initial target for MHV infection and that the wt spreads from initially infected microglia to a variety of cells in an MHVR-independent fashion.",,"['Nakagaki, Keiko', 'Nakagaki, Kazuhide', 'Taguchi, Fumihiro']",,,,
,PMC,"Evaluation of Human Monoclonal Antibody 80R for Immunoprophylaxis of Severe Acute Respiratory Syndrome by an Animal Study, Epitope Mapping, and Analysis of Spike Variants",http://dx.doi.org/10.1128/JVI.79.10.5900-5906.2005,PMC1091676,,,"In this report, the antiviral activity of 80R immunoglobulin G1 (IgG1), a human monoclonal antibody against severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) protein that acts as a viral entry inhibitor in vitro, was investigated in vivo in a mouse model. When 80R IgG1 was given prophylactically to mice at doses therapeutically achievable in humans, viral replication was reduced by more than 4 orders of magnitude to below assay limits. The essential core region of S protein required for 80R binding was identified as a conformationally sensitive fragment (residues 324 to 503) that overlaps the receptor ACE2-binding domain. Amino acids critical for 80R binding were identified. In addition, the effects of various 80R-binding domain amino acid substitutions which occur in SARS-like-CoV from civet cats, and which evolved during the 2002/2003 outbreak and in a 2003/2004 Guangdong index patient, were analyzed. The results demonstrated that the vast majority of SARS-CoVs are sensitive to 80R. We propose that by establishing the susceptibility and resistance profiles of newly emerging SARS-CoVs through early S1 genotyping of the core 180-amino-acid neutralizing epitope of 80R, an effective immunoprophylaxis strategy with 80R should be possible in an outbreak setting. Our study also cautions that for any prophylaxis strategy based on neutralizing antibody responses, whether by passive or active immunization, a genotyping monitor will be necessary for effective use.",,"['Sui, Jianhua', 'Li, Wenhui', 'Roberts, Anjeanette', 'Matthews, Leslie J.', 'Murakami, Akikazu', 'Vogel, Leatrice', 'Wong, Swee Kee', 'Subbarao, Kanta', 'Farzan, Michael', 'Marasco, Wayne A.']",,,,
,PMC,Exploiting cis-Acting Replication Elements To Direct Hepatitis C Virus-Dependent Transgene Expression,http://dx.doi.org/10.1128/JVI.79.10.5923-5932.2005,PMC1091670,,,"We describe here a novel targeting gene therapy strategy to direct gene expression responsive to hepatitis C virus (HCV). The goal was approached by engineering a construct containing the antisense sequence of the transgene and internal ribosome entry site of encephalomyocarditis virus flanked by 5′- and 3′-end sequences of HCV cDNA that contain cis-acting replication elements. Thus, expression of the transgene is only promoted when the minus-strand RNA has been synthesized by the functional replication machinery present in infected cells. Reporter assay and strand-specific reverse transcription-PCR showed selective transgene expression in Huh-7 cells harboring an autonomously replicating HCV subgenome but remaining silent in uninfected cells. Furthermore, using the cytosine deaminase suicide gene as a transgene coupled with recombinant adenovirus delivery, we demonstrated that cytosine deaminase was specifically expressed in replicon cells, resulting in marked chemosensitization of replicon cells to the cytotoxic effects of flucytosine. This new targeting strategy could be extended to other single-stranded RNA viruses encoding the unique RNA-dependent RNA polymerase that has no parallel in mammalian cells.",,"['Zhang, Jing', 'Yamada, Osamu', 'Sakamoto, Takashi', 'Yoshida, Hiroshi', 'Araki, Hiromasa', 'Shimotohno, Kunitada']",,,,
,PMC,Identification of Novel Subgenomic RNAs and Noncanonical Transcription Initiation Signals of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.79.9.5288-5295.2005,PMC1082772,,,"The expression of the genomic information of severe acute respiratory syndrome coronavirus (SARS CoV) involves synthesis of a nested set of subgenomic RNAs (sgRNAs) by discontinuous transcription. In SARS CoV-infected cells, 10 sgRNAs, including 2 novel ones, were identified, which were predicted to be functional in the expression of 12 open reading frames located in the 3′ one-third of the genome. Surprisingly, one new sgRNA could lead to production of a truncated spike protein. Sequence analysis of the leader-body fusion sites of each sgRNA showed that the junction sequences and the corresponding transcription-regulatory sequence (TRS) are unique for each species of sgRNA and are consistent after virus passages. For the two novel sgRNAs, each used a variant of the TRS that has one nucleotide mismatch in the conserved hexanucleotide core (ACGAAC) in the TRS. Coexistence of both plus and minus strands of SARS CoV sgRNAs and evidence for derivation of the sgRNA core sequence from the body core sequence favor the model of discontinuous transcription during minus-strand synthesis. Moreover, one rare species of sgRNA has the junction sequence AAA, indicating that its transcription could result from a noncanonical transcription signal. Taken together, these results provide more insight into the molecular mechanisms of genome expression and subgenomic transcription of SARS CoV.",,"['Hussain, Snawar', ""Pan, Ji'an"", 'Chen, Yu', 'Yang, Yalin', 'Xu, Jing', 'Peng, Yu', 'Wu, Ying', 'Li, Zhaoyang', 'Zhu, Ying', 'Tien, Po', 'Guo, Deyin']",,,,
,PMC,Aged BALB/c Mice as a Model for Increased Severity of Severe Acute Respiratory Syndrome in Elderly Humans,http://dx.doi.org/10.1128/JVI.79.9.5833-5838.2005,PMC1082763,,,"Advanced age has repeatedly been identified as an independent correlate of adverse outcome and a predictor of mortality in cases of severe acute respiratory syndrome (SARS). SARS-associated mortality may exceed 50% for persons aged 60 years or older. Heightened susceptibility of the elderly to severe SARS and the ability of SARS coronavirus to replicate in mice led us to examine whether aged mice might be susceptible to disease. We report here that viral replication in aged mice was associated with clinical illness and pneumonia, demonstrating an age-related susceptibility to SARS disease in animals that parallels the human experience.",,"['Roberts, Anjeanette', 'Paddock, Christopher', 'Vogel, Leatrice', 'Butler, Emily', 'Zaki, Sherif', 'Subbarao, Kanta']",,,,
,PMC,Homologous Crossovers among Molecules of Brome Mosaic Bromovirus RNA1 or RNA2 Segments In Vivo,http://dx.doi.org/10.1128/JVI.79.9.5732-5742.2005,PMC1082739,,,"Previously we demonstrated frequent homologous crossovers among molecules of the RNA3 segment in the tripartite brome mosaic bromovirus (BMV) RNA genome (A. Bruyere, M. Wantroba, S. Flasinski, A. Dzianott, and J. J. Bujarski, J. Virol. 74:4214-4219, 2000). To further our knowledge about mechanisms of viral RNA genome variability, in this paper we have studied homologous recombination in BMV RNA1 and RNA2 components during infection. We have found that basal RNA-RNA crossovers could occur within coding regions of both RNAs, although recombination frequencies slightly varied at different RNA sections. In all cases, the frequencies were much lower than the rate observed for the intercistronic recombination hot spot in BMV RNA3. Probability calculations accounted for at least one homologous crossover per RNA molecule per replication cycle. In addition, we have demonstrated an efficient repair of mutations within the conserved 3′ and 5′ noncoding regions, most likely due to error-prone BMV RNA replication. Overall, our data verify that homologous crossovers are common events a during virus life cycle, and we discuss their importance for viral RNA genetics.",,"['Urbanowicz, Anna', 'Alejska, Magdalena', 'Formanowicz, Piotr', 'Błażewicz, Jacek', 'Figlerowicz, Marek', 'Bujarski, Jozef J.']",,,,
,PMC,"Gamma Interferon-Dependent, Noncytolytic Clearance of Sindbis Virus Infection from Neurons In Vitro",http://dx.doi.org/10.1128/JVI.79.9.5374-5385.2005,PMC1082728,,,"Due to the nonrenewable nature of neurons, recovery from viral infection of the central nervous system requires noncytopathic mechanisms for control of virus replication. Recovery from alphavirus encephalitis can occur without apparent neurological damage through the effects of antibody and gamma interferon (IFN-γ). To establish an in vitro cell culture system that will allow the study of mechanisms of IFN-γ-mediated control of Sindbis virus (SINV) replication in neurons, we have characterized the susceptibility to SINV infection and IFN-γ responsiveness of two neuronal cell lines that can be differentiated in vitro: CSM14.1, a rat nigral cell line, and NSC34, a mouse motor neuron cell line. Undifferentiated CSM14.1 and NSC34 cells were permissive for SINV and susceptible to virus-induced cell death. With differentiation, CSM14.1 cells reduced virus replication and became progressively resistant to virus-induced cell death, resulting in prolonged virus replication. NSC34 cells did not differentiate completely and became only partially resistant to SINV infection. Both CSM14.1 and NSC34 cells responded to pretreatment with IFN-γ by decreasing SINV replication. Differentiated CSM14.1 cells treated 24 h after infection with IFN-γ responded with increased cell viability and clearance of infectious virus. IFN-γ treatment sequentially altered the ratio of genomic to subgenomic viral RNA synthesis, promoted recovery of cellular protein synthesis, reduced viral protein synthesis, and inhibited viral RNA transcription within 24 h after treatment. We conclude that CSM14.1 cells provide an excellent model for the study of IFN-γ-mediated noncytolytic clearance of SINV from mature neurons.",,"['Burdeinick-Kerr, Rebeca', 'Griffin, Diane E.']",,,,
,PMC,Baculovirus as versatile vectors for protein expression in insect and mammalian cells,http://dx.doi.org/10.1038/nbt1095,PMC3610534,,,"Today, many thousands of recombinant proteins, ranging from cytosolic enzymes to membrane-bound proteins, have been successfully produced in baculovirus-infected insect cells. Yet, in addition to its value in producing recombinant proteins in insect cells and larvae, this viral vector system continues to evolve in new and unexpected ways. This is exemplified by the development of engineered insect cell lines to mimic mammalian cell glycosylation of expressed proteins, baculovirus display strategies and the application of the virus as a mammalian-cell gene delivery vector. Novel vector design and cell engineering approaches will serve to further enhance the value of baculovirus technology.",,"['Kost, Thomas A', 'Condreay, J Patrick', 'Jarvis, Donald L']",,,,
,PMC,Circulating endothelial progenitor cells in pulmonary inflammation,http://dx.doi.org/10.1136/thx.2004.037796,PMC1758908,,,,,"Doerschuk, C",,,,
,PMC,"Impact of severe acute respiratory syndrome (SARS) on pulmonary function, functional capacity and quality of life in a cohort of survivors",http://dx.doi.org/10.1136/thx.2004.030205,PMC1758905,,,"Objective: To examine the impact of severe acute respiratory syndrome (SARS) on pulmonary function, exercise capacity, and health-related quality of life (HRQoL) among survivors. Methods: 110 survivors with confirmed SARS were evaluated at the Prince of Wales Hospital, HK at the end of 3 and 6 months after symptom onset. The assessment included lung volumes (TLC, VC, RV, FRC), spirometry (FVC, FEV(1)), carbon monoxide transfer factor (TLCO adjusted for haemoglobin), inspiratory and expiratory respiratory muscle strength (Pimax and Pemax), 6 minute walk distance (6MWD), chest radiographs, and HRQoL by SF-36 questionnaire. Results: There were 44 men and 66 women with a mean (SD) age of 35.6 (9.8) years and body mass index of 23.1 (4.8) kg/m(2). Seventy (64%) were healthcare workers. At 6 months 33 subjects (30%) had abnormal chest radiographs; four (3.6%), eight (7.4%), and 17 (15.5%) patients had FVC, TLC, and TLCO below 80% of predicted values; and 15 (13.9%) and 24 (22.2%) had Pimax and Pemax values below 80 cm H(2)O, respectively. The 6MWD increased from a mean (SD) of 464 (83) m at 3 months to 502 (95) m (95% CI 22 to 54 m, p<0.001), but the results were lower than normal controls in the same age groups. There was impairment of HRQoL at 6 months. Patients who required ICU admission (n = 31) had significantly lower FVC, TLC, and TLCO than those who did not. Conclusion: The exercise capacity and health status of SARS survivors was considerably lower than that of a normal population at 6 months. Significant impairment in surface area for gas exchange was noted in 15.5% of survivors. The functional disability appears out of proportion to the degree of lung function impairment and may be related to additional factors such as muscle deconditioning and steroid myopathy.",,"['Hui, D', 'Joynt, G', 'Wong, K', 'Gomersall, C', 'Li, T', 'Antonio, G', 'Ko, F', 'Chan, M', 'Chan, D', 'Tong, M', 'Rainer, T', 'Ahuja, A', 'Cockram, C', 'Sung, J']",,,,
,PMC,Recovery pathway of post-SARS patients,http://dx.doi.org/10.1136/thx.2004.035972,PMC1758902,,,,,"Chan, J",,,,
,PMC,Surveying the literature from animal experiments: Critical reviews may be helpful—not systematic ones,,PMC557132,,,,,"['Lemon, Roger', 'Dunnett, Stephen B']",,,,
,PMC,Clinical significance of hepatic derangement in severe acute respiratory syndrome,http://dx.doi.org/10.3748/wjg.v11.i14.2148,PMC4305785,,,"AIM: Elevation of alanine aminotransferase (ALT) level is commonly seen among patients suffering from severe acute respiratory syndrome (SARS). We report the progression and clinical significance of liver derangement in a large cohort of SARS patient. METHODS: Serial assay of serum ALT was followed in patients who fulfilled the WHO criteria of SARS. Those with elevated ALT were compared with those with normal liver functions for clinical outcome. Serology for hepatitis B virus (HBV) infection was checked. Adverse outcomes were defined as oxygen desaturation, need of intensive care unit (ICU) and mechanical ventilation and death. RESULTS: Two hundred and ninety-four patients were included in this study. Seventy (24%) patients had elevated serum ALT on admission and 204 (69%) patients had elevated ALT during the subsequent course of illness. Using peak ALT > 5×ULN as a cut-off and after adjusting for potential confounding factors, the odds ratio of peak ALT > 5×ULN for oxygen desaturation was 3.24 (95%CI 1.23-8.59, P = 0.018), ICU care was 3.70 (95%CI 1.38-9.89, P = 0.009), mechanical ventilation was 6.64 (95%CI 2.22-19.81, P = 0.001) and death was 7.34 (95%CI 2.28-24.89, P = 0.001). Ninety-three percent of the survived patients had ALT levels normalized or were on the improving trend during follow-up. Chronic hepatitis B was not associated with worse clinical outcomes. CONCLUSION: Reactive hepatitis is a common complication of SARS-coronavirus infection. Those patients with severe hepatitis had worse clinical outcome.",,"['Chan, Henry Lik-Yuen', 'Kwan, Ambrose Chi-Pong', 'To, Ka-Fai', 'Lai, Sik-To', 'Chan, Paul Kay-Sheung', 'Leung, Wai-Keung', 'Lee, Nelson', 'Wu, Alan', 'Sung, Joseph Jao-Yiu']",,,,
,PMC,Macrophages Rapidly Transfer Pathogens from Lipid Raft Vacuoles to Autophagosomes,,PMC1584280,,,"Macrophages activate autophagy as an immediate response to Legionella pneumophila infection, but what marks the pathogen phagosome as a target for the autophagy machinery is not known. Because a variety of bacteria, parasites, viruses, and toxins that associate with the endoplasmic reticulum enter host cells by a cholesterol-dependent route, we tested the hypothesis that autophagy is triggered when microbes engage components of lipid raft domains. As the intracellular respiratory pathogen L. pneumophila or the extracellular uropathogen FimH(+) Escherichia coli entered macrophages by a cholesterol-sensitive mechanism, they immediatezly resided in vacuoles rich in glycosylphosphatidylinositol moieties and the autophagy enzyme Atg7. As expected for autophagosomes, the vacuoles sequentially acquired the endoplasmic reticulum protein BiP, the autophagy markers Atg8 and monodansyl-cadaverine, and the lysosomal protein LAMP-1. A robust macrophage response to the pathogens was cholesterol-dependent, since fewer Atg7-rich vacuoles were observed when macrophages were pretreated with methyl-β-cyclodextrin or filipin. A model in which macrophages exploit autophagy to capture pathogens within the lipid raft pathway for antigen presentation prior to disposal in lysosomes is discussed.",,"['Amer, Amal O.', 'Byrne, Brenda G.', 'Swanson, Michele S.']",,,,
,PMC,In brief,,PMC555869,,,,,,,,,
,PMC,Jacobson v Massachusetts: It’s Not Your Great-Great-Grandfather’s Public Health Law,http://dx.doi.org/10.2105/AJPH.2004.055160,PMC1449224,,,"Jacobson v Massachusetts, a 1905 US Supreme Court decision, raised questions about the power of state government to protect the public’s health and the Constitution’s protection of personal liberty. We examined conceptions about state power and personal liberty in Jacobson and later cases that expanded, superseded, or even ignored those ideas. Public health and constitutional law have evolved to better protect both health and human rights. States’ sovereign power to make laws of all kinds has not changed in the past century. What has changed is the Court’s recognition of the importance of individual liberty and how it limits that power. Preserving the public’s health in the 21st century requires preserving respect for personal liberty.",,"['Mariner, Wendy K.', 'Annas, George J.', 'Glantz, Leonard H.']",,,,
,PMC,"Manifold Restraints: Liberty, Public Health, and the Legacy of Jacobson v Massachusetts",http://dx.doi.org/10.2105/AJPH.2004.055145,PMC1449222,,,"February 2005 marks the centenary of one of the most important pieces of public health jurisprudence, the US Supreme Court case of Jacobson v Massachusetts, which upheld the authority of states to pass compulsory vaccination laws. The Court’s decision articulated the view that the freedom of the individual must sometimes be subordinated to the common welfare. We examined the relationship between the individual and society in 20th-century public health practice and law and the ways that compulsory measures have been used to constrain personal liberty for the sake of protecting the public health. (Am J Public Health.",,"['Colgrove, James', 'Bayer, Ronald']",,,,
,PMC,Talking About Public Health: Developing America’s “Second Language”,http://dx.doi.org/10.2105/AJPH.2004.043844,PMC1449221,,,"The mission of public health—improving the health of populations—is difficult to advance in public discourse because a language to express the values animating that mission has not been adequately developed. Following on the work of Robert Bellah, Dan Beauchamp, and others, we argue that the first “language” of American culture is individualism. A second American language of community—rooted in egalitarianism, humanitarianism, and human interconnection—serves as the first language of public health. These values resonate with many Americans but are not easily articulated. Consequently, reductionist, individualistic understandings of public health problems prevail. Advancing the public health approach to the nation’s health challenges requires invigorating America’s second language by recognizing the human interconnection underlying the core social justice values of public health.",,"['Wallack, Lawrence', 'Lawrence, Regina']",,,,
,PMC,Chemokine response in children with SARS,http://dx.doi.org/10.1136/adc.2004.053660,PMC1720352,,,,,"['Ng, P', 'Lam, C', 'Li, A', 'Wong, C', 'Leung, T', 'Cheng, F', 'Hon, K', 'Chan, I', 'Wong, E', 'Fok, T']",,,,
,PMC,Retrospective Serological Investigation of Severe Acute Respiratory Syndrome Coronavirus Antibodies in Recruits from Mainland China,http://dx.doi.org/10.1128/CDLI.12.4.552-554.2005,PMC1074388,,,"Different assays were used to analyze 1,621 serum specimens collected from military recruits from the People's Republic of China in 2002 for severe acute respiratory syndrome (SARS) coronavirus antibodies. The results demonstrated that the subjects either had rarely been exposed to the virus before the 2003 SARS outbreak or had not been exposed but the nucleocapsid protein cross-reacted with other antibodies in humans.",,"['Yu, Sumeng', 'Qiu, Maofeng', 'Chen, Zeliang', 'Ye, Xiaobo', 'Gao, Yaling', 'Wei, Aimin', 'Wang, Xiaoyi', 'Yang, Ling', 'Wang, Jin', 'Wen, Jie', 'Song, Yajun', 'Pei, Decui', 'Dai, Erhei', 'Guo, Zhaobiao', 'Cao, Cheng', 'Wang, Jian', 'Yang, Ruifu']",,,,
,PMC,Pathogenesis of Afa/Dr Diffusely Adhering Escherichia coli,http://dx.doi.org/10.1128/CMR.18.2.264-292.2005,PMC1082796,,,"Over the last few years, dramatic increases in our knowledge about diffusely adhering Escherichia coli (DAEC) pathogenesis have taken place. The typical class of DAEC includes E. coli strains harboring AfaE-I, AfaE-II, AfaE-III, AfaE-V, Dr, Dr-II, F1845, and NFA-I adhesins (Afa/Dr DAEC); these strains (i) have an identical genetic organization and (ii) allow binding to human decay-accelerating factor (DAF) (Afa/Dr(DAF) subclass) or carcinoembryonic antigen (CEA) (Afa/Dr(CEA) subclass). The atypical class of DAEC includes two subclasses of strains; the atypical subclass 1 includes E. coli strains that express AfaE-VII, AfaE-VIII, AAF-I, AAF-II, and AAF-III adhesins, which (i) have an identical genetic organization and (ii) do not bind to human DAF, and the atypical subclass 2 includes E. coli strains that harbor Afa/Dr adhesins or others adhesins promoting diffuse adhesion, together with pathogenicity islands such as the LEE pathogenicity island (DA-EPEC). In this review, the focus is on Afa/Dr DAEC strains that have been found to be associated with urinary tract infections and with enteric infection. The review aims to provide a broad overview and update of the virulence aspects of these intriguing pathogens. Epidemiological studies, diagnostic techniques, characteristic molecular features of Afa/Dr operons, and the respective role of Afa/Dr adhesins and invasins in pathogenesis are described. Following the recognition of membrane-bound receptors, including type IV collagen, DAF, CEACAM1, CEA, and CEACAM6, by Afa/Dr adhesins, activation of signal transduction pathways leads to structural and functional injuries at brush border and junctional domains and to proinflammatory responses in polarized intestinal cells. In addition, uropathogenic Afa/Dr DAEC strains, following recognition of β(1) integrin as a receptor, enter epithelial cells by a zipper-like, raft- and microtubule-dependent mechanism. Finally, the presence of other, unknown virulence factors and the way that an Afa/Dr DAEC strain emerges from the human intestinal microbiota as a “silent pathogen” are discussed.",,"Servin, Alain L.",,,,
,PMC,SARS Coronaviruses and Highly Pathogenic Influenza Viruses: Safety and Occupational Health for Laboratory Workers,http://dx.doi.org/10.3201/eid1104.041304,PMC3320340,,NO-CC CODE,,2005 Apr,"['Taylor, Jill', 'Wentworth, David E.', 'Bernard, Kristen A.', 'Masters, Paul S.', 'Trimarchi, Charles V.']",Emerg Infect Dis,,,
,PMC,Emergence and Control of Viral Respiratory Diseases,http://dx.doi.org/10.3201/eid1104.050076,PMC3320327,,NO-CC CODE,,2005 Apr,"['Webster, Robert', 'Plotkin, Stanley', 'Dodet, Betty']",Emerg Infect Dis,,,
,PMC,Third Congress for the European Society for Emerging Infections,http://dx.doi.org/10.3201/eid1104.041297,PMC3320324,,NO-CC CODE,,2005 Apr,"['Mavris, Maria', 'Halos, Lénaïg']",Emerg Infect Dis,,,
,PMC,"Human coronavirus OC43 causes influenza-like illness in residents and staff of aged-care facilities in Melbourne, Australia.",,PMC2870246,,,"Three outbreaks of respiratory illness associated with human coronavirus HCoV-OC43 infection occurred in geographically unrelated aged-care facilities in Melbourne, Australia during August and September 2002. On clinical and epidemiological grounds the outbreaks were first thought to be caused by influenza virus. HCoV-OC43 was detected by RT-PCR in 16 out of 27 (59%) specimens and was the only virus detected at the time of sampling. Common clinical manifestations were cough (74%), rhinorrhoea (59%) and sore throat (53%). Attack rates and symptoms were similar in residents and staff across the facilities. HCoV-OC43 was also detected in surveillance and diagnostic respiratory samples in the same months. These outbreaks establish this virus as a cause of morbidity in aged-care facilities and add to increasing evidence of the significance of coronavirus infections.",,"['Birch, C. J.', 'Clothier, H. J.', 'Seccull, A.', 'Tran, T.', 'Catton, M. C.', 'Lambert, S. B.', 'Druce, J. D.']",,,,
,PMC,Immune responses induced by intranasal imiquimod and implications for therapeutics in rhinovirus infections,http://dx.doi.org/10.1111/j.1582-4934.2005.tb00370.x,PMC6740272,,,"Notwithstanding the progress recently made in immunology and virology, there is yet no effective, specific treatment for the common cold. Symptomatic treatment is minimally effective. An anecdotal report of rapid clearing of the common cold of recent onset after intranasal application of imiquimod in several subjects by one of the authors, made us test the hypothesis that this treatment works through the secretion of interferon by the nasal mucosa. We decided to do an animal study in primates (Indian Macaca Mulata): 5 treatment and 3 control animals were used. Imiquimod or placebo was massaged into the nares of the animals and periodic samples of post‐nasal fluid were taken and measurements for Interferon α (IFNα) and Tumor Necrosis Factor α (TNFα) were made by ELISA methods, and kinetic studies. IFNα mRNA was also isolated and analyzed by quantitative competitive RT‐PCR. The internal standard was constructed to be complementary to and compete with oligonucleotide primers and for amplification of target sequences. One intranasal application of imiquimod rapidly (1–4 h) induced high levels of mRNA for IFNα, and minimal levels in the control animals. Rapid induction of INFα, and proportional increase of TNFα sustained for 4 and 6 h respectively were noted. No adverse reactions to treatment were found in macaques during this short period of intranasal imiquimod usage (except in one macaque with a short period of lacrimation). No animal had cytotoxic effects when examined at 6 h, 12 h, 24 h or 48 h, except one animal, which had an episode of lacrimation for 6hr post treatment. Thus both safety and efficacy of short treatment with imiquimod is proven in this animal model. Proof of principle for intranasal treatment of the common cold with imiquimod is shown. We think that this work will encourage a number of double blind clinical trials to confirm the effectiveness of the intranasal treatment of the common cold with imiquimod.",,"['Clejan, Sanda', 'Mandrea, E.', 'Pandrea, Ivona V.', 'Dufour, J.', 'Japa, S.', 'Veazey, R. S.']",,,,
,PMC,Development and Application of a Saccharomyces cerevisiae-Expressed Nucleocapsid Protein-Based Enzyme-Linked Immunosorbent Assay for Detection of Antibodies against Infectious Bronchitis Virus,http://dx.doi.org/10.1128/JCM.43.4.1982-1984.2005,PMC1081331,,,"A Saccharomyces cerevisiae-expressed nucleocapsid (N) polypeptide of the M41 strain of infectious bronchitis virus (IBV) was used as antigen in a recombinant yeast-expressed N protein-based enzyme-linked immunosorbent assay (Y-N-ELISA). The Y-N-ELISA was rapid, sensitive, and specific for detecting chicken serum antibodies to IBV, and it compared favorably with a commercial ELISA.",,"['Gibertoni, Aliandra M.', 'Montassier, Maria de Fátima S.', 'Sena, Janete A. D.', 'Givisiez, Patrícia E. N.', 'Furuyama, Cibele R. A. G.', 'Montassier, Hélio J.']",,,,
,PMC,System To Assess Genome Sequencing Needs for Viral Protein Diagnostics and Therapeutics,http://dx.doi.org/10.1128/JCM.43.4.1807-1817.2005,PMC1081307,,,"Computational analyses of genome sequences may elucidate protein signatures unique to a target pathogen. We constructed a Protein Signature Pipeline to guide the selection of short peptide sequences to serve as targets for detection and therapeutics. In silico identification of good target peptides that are conserved among strains and unique compared to other species generates a list of peptides. These peptides may be developed in the laboratory as targets of antibody, peptide, and ligand binding for detection assays and therapeutics or as targets for vaccine development. In this paper, we assess how the amount of sequence data affects our ability to identify conserved, unique protein signature candidates. To determine the amount of sequence data required to select good protein signature candidates, we have built a computationally intensive system called the Sequencing Analysis Pipeline (SAP). The SAP performs thousands of Monte Carlo simulations, each calling the Protein Signature Pipeline, to assess how the amount of sequence data for a target organism affects the ability to predict peptide signature candidates. Viral species differ substantially in the number of genomes required to predict protein signature targets. Patterns do not appear based on genome structure. There are more protein than DNA signatures due to greater intraspecific conservation at the protein than at the nucleotide level. We conclude that it is necessary to use the SAP as a dynamic system to assess the need for continued sequencing for each species individually and to update predictions with each additional genome that is sequenced.",,"['Gardner, Shea N.', 'Kuczmarski, Thomas A.', 'Zhou, Carol E.', 'Lam, Marisa W.', 'Slezak, Tom R.']",,,,
,PMC,Using volunteers in Ontario hospital libraries: views of library managers,,PMC1082943,,,"Background: Volunteers have been a resource for all types of libraries for many years. Little research has been done to describe the attitudes librarians have toward library volunteers. More specifically, the attitudes of hospital librarians toward volunteers have never been studied. Objective: The objective was to explore and describe the extent of volunteer use and to determine library managers' attitudes toward volunteers. Design, Setting, and Participants: An anonymous, self-report 38-item questionnaire was mailed to the target population of 89 hospital library managers in Ontario. Seventy-nine useable questionnaires were analyzed from an adjusted sample of 86 eligible respondents, resulting in a response rate of 92%. SPSS 11.5 was used to analyze the data. Findings: The data revealed the attitudes of managers using volunteers did not differ significantly from the attitudes of managers not using volunteers. The findings showed that a majority of managers did not believe their libraries were adequately staffed with paid employees. Sufficient evidence was found of an association between a manager's belief in the adequacy of staffing in the library and the use of volunteers in the library (χ(2)(1, N = 76) = 4.11, P = 0.043). Specifically, volunteers were more likely to be used by managers who did not believe their libraries were adequately staffed. The presence of a union in the library and the use of volunteers were also associated (χ(2)(1, N = 77) = 4.77, P = 0.029). When unions were present in the library, volunteers were less likely to be used. Implications: This research has implications for hospital library managers in the management of volunteers. Volunteers should not be viewed as a quick fix or as a long-term solution for a library's understaffing problem.",,"['McDiarmid, Mary', 'Auster, Ethel']",,,,
,PMC,Expression of Matrix Metalloproteinases and Their Tissue Inhibitor during Viral Encephalitis,http://dx.doi.org/10.1128/JVI.79.8.4764-4773.2005,PMC1069551,,,"Matrix metalloproteinases (MMPs) participate in remodeling the extracellular matrix and facilitate entry of inflammatory cells into tissues. Infection of the murine central nervous system (CNS) with a neurotropic coronavirus induces encephalitis associated with increased levels of mRNA encoding MMP-3 and MMP-12. Whereas virus-induced MMP-3 expression was restricted to CNS resident astrocytes, MMP-12 mRNA was expressed by both inflammatory cells and CNS resident cells. Immunosuppression increased both MMP-3 and MMP-12 mRNA levels in CNS resident cells, suggesting that the presence of virus rather than inflammation induced protease up-regulation. MMP activity is partially regulated by a small family of genes encoding tissue inhibitors of matrix metalloproteinases (TIMPs); among the TIMPs, only TIMP-1 mRNA expression increased in the CNS following coronavirus infection. During inflammation TIMP-1 mRNA was most prominently expressed by infiltrating cells. By contrast, in the immunosuppressed host TIMP-1 mRNA was expressed by CNS resident cells. Analysis of cytokine and chemokine mRNA induction within the infected CNS of healthy and immunocompromised mice suggested a possible correlation between increased viral replication and increased levels of beta interferon, MMP-3, MMP-12, and TIMP-1 mRNA. CD4(+) T cells which localize to the perivascular and subarachnoid spaces were identified as the primary source of TIMP-1 protein. By contrast, protein expression was undetectable in astrocytes or CD8(+) T cells, the primary antiviral effectors that localize to the CNS parenchyma in response to infection. These data suggest that in contrast to the results seen with MMPs, inhibition of protease activity via TIMP-1 expression correlates with the differential tissue distribution of T-cell subsets during acute coronavirus-induced encephalitis.",,"['Zhou, Jiehao', 'Marten, Norman W.', 'Bergmann, Cornelia C.', 'Macklin, Wendy B.', 'Hinton,  David R.', 'Stohlman, Stephen A.']",,,,
,PMC,Virus-Specific and Bystander CD8 T Cells Recruited during Virus-Induced Encephalomyelitis,http://dx.doi.org/10.1128/JVI.79.8.4700-4708.2005,PMC1069536,,,"Neurotropic coronavirus-induced encephalitis was used to evaluate recruitment, functional activation, and retention of peripheral bystander memory CD8(+) T cells. Mice were first infected with recombinant vaccinia virus expressing a non-cross-reactive human immunodeficiency virus (HIV) epitope, designated p18. Following establishment of an endogenous p18-specific memory CD8(+) T-cell population, mice were challenged with coronavirus to directly compare recruitment, longevity, and activation characteristics of both primary coronavirus-specific and bystander memory populations trafficking into the central nervous system (CNS). HIV-specific memory CD8(+) T cells were recruited early into the CNS as components of the innate immune response, preceding CD8(+) T cells specific for the dominant coronavirus epitope, designated pN. Although pN-specific T-cell numbers gradually exceeded bystander p18-specific CD8(+) T-cell numbers, both populations peaked concurrently within the CNS. Nevertheless, coronavirus-specific CD8(+) T cells were preferentially retained. By contrast, bystander CD8(+) T-cell numbers declined to background numbers following control of CNS virus replication. Furthermore, in contrast to highly activated pN-specific CD8(+) T cells, bystander p18-specific CD8(+) T cells recruited to the site of inflammation maintained a nonactivated memory phenotype and did not express ex vivo cytolytic activity. Therefore, analysis of host CD8(+) T-cell responses to unrelated infections demonstrates that bystander memory CD8(+) T cells can comprise a significant proportion of CNS inflammatory cells during virus-induced encephalitis. However, transient CNS retention and the absence of activation suggest that memory bystander CD8(+) T cells may not overtly contribute to pathology in the absence of antigen recognition.",,"['Chen, Audrey M.', 'Khanna, Nivedita', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.']",,,,
,PMC,"Deubiquitination, a New Function of the Severe Acute Respiratory Syndrome Coronavirus Papain-Like Protease?",http://dx.doi.org/10.1128/JVI.79.7.4550-4551.2005,PMC1061586,,,,,"['Sulea, Traian', 'Lindner, Holger A.', 'Purisima, Enrico O.', 'Ménard, Robert']",,,,
,PMC,Viral Induction of Central Nervous System Innate Immune Responses,http://dx.doi.org/10.1128/JVI.79.7.4369-4381.2005,PMC1061546,,,"The ability of the central nervous system (CNS) to generate innate immune responses was investigated in an in vitro model of CNS infection. Cultures containing CNS cells were infected with mouse hepatitis virus-JHM, which causes fatal encephalitis in mice. Immunostaining indicated that viral infection had a limited effect on culture characteristics, overall cell survival, or cell morphology at the early postinfection times studied. Results from Affymetrix gene array analysis, assessed on RNA isolated from virally and sham-infected cultures, were compared with parallel protein assays for cytokine, chemokine, and cell surface markers. Of the 126 transcripts found to be differentially expressed between viral and sham infections, the majority were related to immunological responses. Virally induced increases in interleukin-6 and tumor necrosis factor alpha mRNA and protein expression correlated with the genomic induction of acute-phase proteins. Genomic and protein analysis indicated that viral infection resulted in prominent expression of neutrophil and macrophage chemotactic proteins. In addition, mRNA expression of nonclassical class I molecules H2-T10, -T17, -M2, and -Q10, were enhanced three- to fivefold in virus-infected cells compared to sham-infected cells. Thus, upon infection, resident brain cells induced a breadth of innate immune responses that could be vital in directing the outcome of the infection and, in vivo, would provide signals which would summon the peripheral immune system to respond to the infection. Further understanding of how these innate responses participate in immune protection or immunopathology in the CNS will be critical in efforts to intervene in severe encephalitis.",,"['Rempel, J. D.', 'Quina, L. A.', 'Blakely-Gonzales, P. K.', 'Buchmeier, M. J.', 'Gruol, D. L.']",,,,
,PMC,Facts and ideas from anywhere,,PMC1200725,,,,,"Roberts, William Clifford",,,,
,PMC,Plague: from natural disease to bioterrorism,,PMC1200711,,,"Yersinia pestis is the causative agent of plague, an enzootic vectorborne disease usually infecting rodents (rats) and fleas. Humans can become infected after being bitten by fleas that have fed on infected rodents. In humans, the disease usually occurs in the form of bubonic plague. In rare cases, the infection spreads to the lungs via the bloodstream and causes secondary pneumonic plague. Person-to-person transmission has been described for pneumonic plague but is rare in primary bubonic plague. Bubonic plague can usually be treated successfully with antibiotics; however, pneumonic plague develops rapidly and carries a high fatality rate despite immediate treatment with antibiotics. Plague is also recognized as a potential agent of bioterrorism. It has been used, or considered for use, as a biologic weapon on several occasions. It is important for the medical community to be familiar with the epidemiology, diagnosis, and symptoms of plague so it can deliver an appropriate and calm response should the unthinkable happen.",,"Riedel, Stefan",,,,
,PMC,Democracy and health,http://dx.doi.org/10.1093/qjmed/hci042,PMC4006218,,,,,"RUGER, J.P.",,,,
,PMC,Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2,http://dx.doi.org/10.1038/sj.emboj.7600640,PMC1142572,,,"Human angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS coronavirus (SARS-CoV). Here we identify the SARS-CoV spike (S)-protein-binding site on ACE2. We also compare S proteins of SARS-CoV isolated during the 2002–2003 SARS outbreak and during the much less severe 2003–2004 outbreak, and from palm civets, a possible source of SARS-CoV found in humans. All three S proteins bound to and utilized palm-civet ACE2 efficiently, but the latter two S proteins utilized human ACE2 markedly less efficiently than did the S protein obtained during the earlier human outbreak. The lower affinity of these S proteins could be complemented by altering specific residues within the S-protein-binding site of human ACE2 to those of civet ACE2, or by altering S-protein residues 479 and 487 to residues conserved during the 2002–2003 outbreak. Collectively, these data describe molecular interactions important to the adaptation of SARS-CoV to human cells, and provide insight into the severity of the 2002–2003 SARS epidemic.",,"['Li, Wenhui', 'Zhang, Chengsheng', 'Sui, Jianhua', 'Kuhn, Jens H', 'Moore, Michael J', 'Luo, Shiwen', 'Wong, Swee-Kee', 'Huang, I-Chueh', 'Xu, Keming', 'Vasilieva, Natalya', 'Murakami, Akikazu', 'He, Yaqing', 'Marasco, Wayne A', 'Guan, Yi', 'Choe, Hyeryun', 'Farzan, Michael']",,,,
,PMC,WHO reinvigorates role to fight 'big three' diseases.,,PMC2624207,,,,,"Chow, Jack C.",,,,
,PMC,"Virus-Specific Antibody, in the Absence of T Cells, Mediates Demyelination in Mice Infected with a Neurotropic Coronavirus",,PMC1602352,,,"Mice infected with mouse hepatitis virus strain JHM develop an inflammatory demyelinating disease in the central nervous system with many similarities to human multiple sclerosis. The mouse disease is primarily immune-mediated because demyelination is not detected in JHM-infected mice lacking T or B cells but does occur after transfer of JHM-specific T cells. Although less is known about the ability of antibodies to mediate demyelination, the presence of oligoclonally expanded B cells and high concentrations of antibodies (against self or infectious agents) in the central nervous system of many multiple sclerosis patients suggests that antibodies may also contribute to myelin destruction. Here, we show that anti-JHM antibodies, in the absence of T or B cells, caused demyelination in JHM-infected mice. Anti-JHM antibody was detected adjacent to areas of demyelination, consistent with a direct interaction between antibody and infected cells. Demyelination was reduced by 85 to 90% in infected RAG1(−/−) mice lacking normal expression of activating Fc receptors (FcRγ(−/−)) and by ∼76% when complement was depleted by treatment with cobra venom factor. These data demonstrate that JHM-specific antibodies are sufficient to cause demyelination and that myelin destruction in the presence of anti-virus antibodies results from a combination of complement- and Fc receptor-dependent mechanisms.",,"['Kim, Taeg S.', 'Perlman, Stanley']",,,,
,PMC,Ecological Change and the Future of the Human Species: Can Physicians Make a Difference?,http://dx.doi.org/10.1370/afm.271,PMC1466851,,,"Global environmental change is occurring so rapidly that it is affecting the health and threatening the future of many of Earth’s inhabitants, including human beings. Global warming; contamination of the air, water, and soil; and rampant deforestation have led to a collapse in biodiversity that threatens the integrity of the biophysical systems upon which all organisms depend. A basic cause of environmental degradation is human overpopulation and the nonsustainable consumption of natural resources by the human community. Everything that we have accomplished in the fields of medicine and public health could be undermined if we do not pay attention to these rapid environmental changes. As healers, human beings, and members of the biological community, we need to broaden our perspective on health and disease. Unless we devote our attention to stabilizing and repairing the ecosystem, our professional and personal accomplishments as health professionals may be swept away. Health care providers—particularly physicians—can play a role by adopting an ecosystem health perspective as we ply our trade. By helping people avoid unwanted pregnancies, by using resources parsimoniously, and by staying engaged in the natural world, we can help to prevent the collapse of the biological systems upon which we all depend.",,"Rosenblatt, Roger A.",,,,
,PMC,The severe acute respiratory syndrome coronavirus in tears,http://dx.doi.org/10.1136/bjo.2004.054130,PMC1772561,,,,,"['Tong, T', 'Lai, T Sik-to']",,,,
,PMC,Use of the COOH Portion of the Nucleocapsid Protein in an Antigen-Capturing Enzyme-Linked Immunosorbent Assay for Specific and Sensitive Detection of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/CDLI.12.3.474-476.2005,PMC1065208,,,"Antibody detection with a recombinant COOH portion of the severe acute respiratory syndrome (SARS) coronavirus nucleocapsid (N) protein, N13 (amino acids 221 to 422), was demonstrated to be more specific and sensitive than that with the full-length N protein, and an N13-based antigen-capturing enzyme-linked immunosorbent assay providing a convenient and specific test for serodiagnosis and epidemiological study of SARS was developed.",,"['Qiu, Maofeng', 'Wang, Jin', 'Wang, Hongxia', 'Chen, Zeliang', 'Dai, Erhei', 'Guo, Zhaobiao', 'Wang, Xiaoyi', 'Pang, Xin', 'Fan, Baoxing', 'Wen, Jie', 'Wang, Jian', 'Yang, Ruifu']",,,,
,PMC,Author Index,http://dx.doi.org/10.1111/j.1365-2249.2004.02787.x,PMC1809317,,,,,,,,,
,PMC,Licking latency with licorice,http://dx.doi.org/10.1172/JCI200524507,PMC1052015,,,"Numerous viruses cause latent infections in humans, and reactivation often results in pain and suffering. While vaccines for several of these viruses are available or currently being studied in clinical trials, and antiviral therapies have been successful in preventing or treating active infection, therapy to eradicate latent infection has lagged behind. A new study reported in this issue of the JCI shows that treatment of cells latently infected with Kaposi sarcoma–associated herpesvirus (KSHV) with glycyrrhizic acid, a component of licorice, reduces synthesis of a viral latency protein and induces apoptosis of infected cells. This finding suggests a novel way to interrupt latency.",,"Cohen, Jeffrey I.",,,,
,PMC,"Glycyrrhizic acid alters Kaposi sarcoma–associated herpesvirus latency, triggering p53-mediated apoptosis in transformed B lymphocytes",http://dx.doi.org/10.1172/JCI200523334,PMC1051998,,,"Kaposi sarcoma–associated herpesvirus (KSHV) is linked with all clinical forms of Kaposi sarcoma and several lymphoproliferative disorders. Like other herpesviruses, KSHV becomes latent in the infected cells, expressing only a few genes that are essential for the establishment and maintenance of its latency and for the survival of the infected cells. Inhibiting the expression of these latent genes should lead to eradication of herpesvirus infection. All currently available drugs are ineffective against latent infection. Here we show, for the first time to our knowledge, that latent infection with KSHV in B lymphocytes can be terminated by glycyrrhizic acid (GA), a triterpenoid compound earlier shown to inhibit the lytic replication of other herpesviruses. We demonstrate that GA disrupts latent KSHV infection by downregulating the expression of latency-associated nuclear antigen (LANA) and upregulating the expression of viral cyclin and selectively induces cell death of KSHV-infected cells. We show that reduced levels of LANA lead to p53 reactivation, an increase in ROS, and mitochondrial dysfunction, which result in G(1) cell cycle arrest, DNA fragmentation, and oxidative stress–mediated apoptosis. Latent genes are involved in KSHV-induced oncogenesis, and strategies to interfere with their expression might prove useful for eradicating latent KSHV infection and have future therapeutic implications.",,"['Curreli, Francesca', 'Friedman-Kien, Alvin E.', 'Flore, Ornella']",,,,
,PMC,Detection of Human Metapneumovirus RNA Sequences in Nasopharyngeal Aspirates of Young French Children with Acute Bronchiolitis by Real-Time Reverse Transcriptase PCR and Phylogenetic Analysis,http://dx.doi.org/10.1128/JCM.43.3.1411-1414.2005,PMC1081260,,,"Human metapneumovirus (HMPV) was the unique viral pathogen detected by a real-time reverse transcriptase PCR (RT-PCR) assay in 6 (6.4%) of 94 consecutive French children hospitalized for acute bronchiolitis from September 2001 to June 2002. This virus was identified as the third etiological cause of bronchiolitis, after respiratory syncytial virus and rhinovirus (35 [37%] and 21 [22%] of 94 cases, respectively). Phylogenetic analysis of F-gene sequences demonstrated the cocirculation of distinct HMPV genotypes during this study. These findings highlight the need to implement a rapid HMPV RT-PCR detection assay for the clinical diagnosis of respiratory infections in pediatric patients with bronchiolitis.",,"['Bouscambert-Duchamp, Maude', 'Lina, Bruno', 'Trompette, Aurélien', 'Moret, Hélène', 'Motte, Jacques', 'Andréoletti, Laurent']",,,,
,PMC,Fatal Peritonitis Caused by Pasteurella multocida Capsular Type F in Calves,http://dx.doi.org/10.1128/JCM.43.3.1480-1483.2005,PMC1081243,,,"A fatal case of atypical septicemia of pasteurellosis in veal calves is described. The causative organism was identified as a multiresistant Pasteurella multocida capsular type F isolate. The outbreak was characterized by fibrinous peritonitis and mortality, which are hitherto unreported features of P. multocida capsular type F infections.",,"['Catry, Boudewijn', 'Chiers, Koen', 'Schwarz, Stefan', 'Kehrenberg, Corinna', 'Decostere, Annemie', 'de Kruif, Aart']",,,,
,PMC,Development of a quantitative assay for SARS coronavirus and correlation of GAPDH mRNA with SARS coronavirus in clinical specimens,http://dx.doi.org/10.1136/jcp.2004.016592,PMC1770583,,,"Aims: To develop a quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR) for severe acute respiratory syndrome coronavirus (SARS-CoV) detection and explore the potential of using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA as an internal control to exclude false negative results. Methods: SARS-CoV and GAPDH mRNA were both measured in 26 specimens from 16 patients with SARS, 40 follow up specimens from the same batch of patients, and appropriate control subjects. The relation between SARS positivity and GAPDH mRNA concentration was investigated using the χ(2) test. Increasing the sensitivity for SARS-CoV and GAPDH mRNA detection was investigated in follow up specimens in which SARS-CoV and GAPDH mRNA were not detected initially. Results: Varying amounts of SARS-CoV were found in the 26 SARS-CoV positive specimens and SARS-CoV was not detected in the 40 follow up specimens and controls. In addition, concentrations of GAPDH mRNA were significantly different between the patients with SARS, follow up specimens, and healthy controls (Kruskal-Wallis test, p<0.05). Moreover, GAPDH mRNA concentrations were highly correlated with SARS-CoV positivity (χ(2) = 5.43; p<0.05). Finally, SARS-CoV and GAPDH mRNA were both detected in three follow up urine specimens that were initially negative when the amount of cDNA used was increased from 5 μl to 10 and 15 μl. Conclusions: This Q-RT-PCR assay can be used to detect SARS-CoV. Moreover, GAPDH mRNA may be useful to rule out false negative results in SARS-CoV detection, and the current extraction method for urine may not be sensitive enough to detect low titres of SARS-CoV.",,"['Wong, S C C', 'Chan, J K C', 'Lee, K C', 'Lo, E S F', 'Tsang, D N C']",,,,
,PMC,An initial investigation of the association between the SARS outbreak and weather: with the view of the environmental temperature and its variation,http://dx.doi.org/10.1136/jech.2004.020180,PMC1733040,,,"Objective: To understand the association between the SARS outbreak and the environmental temperature, and to provide a scientific basis for prevention and control measures against it. Methods: The daily numbers of the probable SARS patients and the daily meteorological factors during the SARS outbreak period in Hong Kong, Guangzhou, Beijing, and Taiyuan were used in the data analysis. Ecological analysis was conducted to explore the association between the daily numbers of probable SARS patients and the environmental temperature and its variations. Results: There was a significant correlation between the SARS cases and the environmental temperature seven days before the onset and the seven day time lag corresponds well with the known incubation period for SARS. The optimum environmental temperature associated with the SARS cases was between 16°C to 28°C, which may encourage virus growth. A sharp rise or decrease in the environmental temperature related to the cold spell led to an increase of the SARS cases because of the possible influence of the weather on the human immune system. This study provided some evidence that there is a higher possibility for SARS to reoccur in spring than that in autumn and winter. Conclusion: Current knowledge based on case studies of the SARS outbreak in the four cities suggested that the SARS outbreaks were significantly associated with the temperature and its variations. However, because the fallacy and the uncontrolled confounding effects might have biased the results, the possibility of other meteorological factors having an affect on the SARS outbreaks deserves further investigation.",,"['Tan, J.', 'Mu, L.', 'Huang, J.', 'Yu, S.', 'Chen, B.', 'Yin, J.']",,,,
,PMC,Nuclear Localization of Japanese Encephalitis Virus Core Protein Enhances Viral Replication,http://dx.doi.org/10.1128/JVI.79.6.3448-3458.2005,PMC1075736,,,"Japanese encephalitis virus (JEV) core protein was detected in both the nucleoli and cytoplasm of mammalian and insect cell lines infected with JEV or transfected with the expression plasmid of the core protein. Mutation analysis revealed that Gly(42) and Pro(43) in the core protein are essential for the nuclear and nucleolar localization. A mutant M4243 virus in which both Gly(42) and Pro(43) were replaced by Ala was recovered by plasmid-based reverse genetics. In C6/36 mosquito cells, the M4243 virus exhibited RNA replication and protein synthesis comparable to wild-type JEV, whereas propagation in Vero cells was impaired. The mutant core protein was detected in the cytoplasm but not in the nucleus of either C6/36 or Vero cell lines infected with the M4243 virus. The impaired propagation of M4243 in mammalian cells was recovered by the expression of wild-type core protein in trans but not by that of the mutant core protein. Although M4243 mutant virus exhibited a high level of neurovirulence comparable to wild-type JEV in spite of the approximately 100-fold-lower viral propagation after intracerebral inoculation to 3-week-old mice of strain Jcl:ICR, no virus was recovered from the brain after intraperitoneal inoculation of the mutant. These results indicate that nuclear localization of JEV core protein plays crucial roles not only in the replication in mammalian cells in vitro but also in the pathogenesis of encephalitis induced by JEV in vivo.",,"['Mori, Yoshio', 'Okabayashi, Tamaki', 'Yamashita, Tetsuo', 'Zhao, Zijiang', 'Wakita, Takaji', 'Yasui, Kotaro', 'Hasebe, Futoshi', 'Tadano, Masayuki', 'Konishi, Eiji', 'Moriishi, Kohji', 'Matsuura, Yoshiharu']",,,,
,PMC,Amino Acids 1055 to 1192 in the S2 Region of Severe Acute Respiratory Syndrome Coronavirus S Protein Induce Neutralizing Antibodies: Implications for the Development of Vaccines and Antiviral Agents,http://dx.doi.org/10.1128/JVI.79.6.3289-3296.2005,PMC1075733,,,"The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) interacts with cellular receptors to mediate membrane fusion, allowing viral entry into host cells; hence it is recognized as the primary target of neutralizing antibodies, and therefore knowledge of antigenic determinants that can elicit neutralizing antibodies could be beneficial for the development of a protective vaccine. Here, we expressed five different fragments of S, covering the entire ectodomain (amino acids 48 to 1192), as glutathione S-transferase fusion proteins in Escherichia coli and used the purified proteins to raise antibodies in rabbits. By Western blot analysis and immunoprecipitation experiments, we showed that all the antibodies are specific and highly sensitive to both the native and denatured forms of the full-length S protein expressed in virus-infected cells and transfected cells, respectively. Indirect immunofluorescence performed on fixed but unpermeabilized cells showed that these antibodies can recognize the mature form of S on the cell surface. All the antibodies were also able to detect the maturation of the 200-kDa form of S to the 210-kDa form by pulse-chase experiments. When the antibodies were tested for their ability to inhibit SARS-CoV propagation in Vero E6 culture, it was found that the anti-SΔ10 antibody, which was targeted to amino acid residues 1029 to 1192 of S, which include heptad repeat 2, has strong neutralizing activities, suggesting that this region of S carries neutralizing epitopes and is very important for virus entry into cells.",,"['Keng, Choong-Tat', 'Zhang, Aihua', 'Shen, Shuo', 'Lip, Kuo-Ming', 'Fielding, Burtram C.', 'Tan, Timothy H. P.', 'Chou, Chih-Fong', 'Loh, Chay Boon', 'Wang, Sifang', 'Fu, Jianlin', 'Yang, Xiaoming', 'Lim, Seng Gee', 'Hong, Wanjin', 'Tan, Yee-Joo']",,,,
,PMC,Single-Amino-Acid Substitutions in Open Reading Frame (ORF) 1b-nsp14 and ORF 2a Proteins of the Coronavirus Mouse Hepatitis Virus Are Attenuating in Mice,http://dx.doi.org/10.1128/JVI.79.6.3391-3400.2005,PMC1075728,,,"A reverse genetic system was recently established for the coronavirus mouse hepatitis virus strain A59 (MHV-A59), in which cDNA fragments of the RNA genome are assembled in vitro into a full-length genome cDNA, followed by electroporation of in vitro-transcribed genome RNA into cells with recovery of viable virus. The “in vitro-assembled” wild-type MHV-A59 virus (icMHV-A59) demonstrated replication identical to laboratory strains of MHV-A59 in tissue culture; however, icMHV-A59 was avirulent following intracranial inoculation of C57BL/6 mice. Sequencing of the cloned genome cDNA fragments identified two single-nucleotide mutations in cloned genome fragment F, encoding a Tyr6398His substitution in open reading frame (ORF) 1b p59-nsp14 and a Leu94Pro substitution in the ORF 2a 30-kDa protein. The mutations were repaired individually and together in recombinant viruses, all of which demonstrated wild-type replication in tissue culture. Following intracranial inoculation of mice, the viruses encoding Tyr6398His/Leu94Pro substitutions and the Tyr6398His substitution alone demonstrated log(10) 50% lethal dose (LD(50)) values too great to be measured. The Leu94Pro mutant virus had reduced but measurable log(10) LD(50), and the “corrected” Tyr6398/Leu94 virus had a log(10) LD(50) identical to wild-type MHV-A59. The experiments have defined residues in ORF 1b and ORF 2a that attenuate virus replication and virulence in mice but do not affect in vitro replication. The results suggest that these proteins serve roles in pathogenesis or virus survival in vivo distinct from functions in virus replication. The study also demonstrates the usefulness of the reverse genetic system to confirm the role of residues or proteins in coronavirus replication and pathogenesis.",,"['Sperry, Steven M.', 'Kazi, Lubna', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Weiss, Susan R.', 'Denison, Mark R.']",,,,
,PMC,Increased Epitope-Specific CD8(+) T Cells Prevent Murine Coronavirus Spread to the Spinal Cord and Subsequent Demyelination,http://dx.doi.org/10.1128/JVI.79.6.3370-3381.2005,PMC1075721,,,"CD8(+) T cells are important for clearance of neurotropic mouse hepatitis virus (MHV) strain A59, although their possible role in A59-induced demyelination is not well understood. We developed an adoptive-transfer model to more clearly elucidate the role of virus-specific CD8(+) T cells during the acute and chronic phases of infection with A59 that is described as follows. C57BL/6 mice were infected with a recombinant A59 virus expressing the gp33 epitope, an H-2D(b)-restricted CD8(+) T-cell epitope encoded in the glycoprotein of lymphocytic choriomeningitis virus, as a fusion with the enhanced green fluorescent protein (RA59-gfp/gp33). P14 splenocytes (transgenic for a T-cell receptor specific for the gp33 epitope) were transferred at different times pre- and postinfection (p.i.). Adoptive transfer of P14 splenocytes 1 day prior to infection with RA59-gfp/gp33, but not control virus lacking the gp33 epitope, RA59-gfp, reduced weight loss and viral replication and spread in the brain and to the spinal cord. Furthermore, demyelination was significantly reduced compared to that in nonrecipients. However, when P14 cells were transferred on day 3 or 5 p.i., no difference in acute or chronic disease was observed compared to that in nonrecipients. Protection in mice receiving P14 splenocytes prior to infection correlated with a robust gp33-specific immune response that was not observed in mice receiving the later transfers. Thus, an early robust CD8(+) T-cell response was necessary to reduce virus replication and spread, specifically to the spinal cord, which protected against demyelination in the chronic phase of the disease.",,"['MacNamara, Katherine C.', 'Chua, Ming Ming', 'Nelson, Peter T.', 'Shen, Hao', 'Weiss, Susan R.']",,,,
,PMC,Exogenous ACE2 Expression Allows Refractory Cell Lines To Support Severe Acute Respiratory Syndrome Coronavirus Replication,http://dx.doi.org/10.1128/JVI.79.6.3846-3850.2005,PMC1075706,,,"Of 30 cell lines and primary cells examined, productive severe acute respiratory syndrome coronavirus (Urbani strain) (SARS-CoV) infection after low-multiplicity inoculation was detected in only six: three African green monkey kidney epithelial cell lines (Vero, Vero E6, and MA104), a human colon epithelial line (CaCo-2), a porcine kidney epithelial line [PK(15)], and mink lung epithelial cells (Mv 1 Lu). SARS-CoV produced a lytic infection in Vero, Vero E6, and MA104 cells, but there was no visible cytopathic effect in Caco-2, Mv 1 Lu, or PK(15) cells. Multistep growth kinetics were identical in Vero E6 and MA104 cells, with maximum titer reached 24 h postinoculation (hpi). Virus titer was maximal 96 hpi in CaCo-2 cells, and virus was continually produced from infected CaCo-2 cells for at least 6 weeks after infection. CaCo-2 was the only human cell type of 13 tested that supported efficient SARS-CoV replication. Expression of the SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2), resulted in SARS-CoV replication in all refractory cell lines examined. Titers achieved were variable and dependent upon the method of ACE2 expression.",,"['Mossel, Eric C.', 'Huang, Cheng', 'Narayanan, Krishna', 'Makino, Shinji', 'Tesh, Robert B.', 'Peters, C. J.']",,,,
,PMC,B-Cell Responses in Patients Who Have Recovered from Severe Acute Respiratory Syndrome Target a Dominant Site in the S2 Domain of the Surface Spike Glycoprotein,http://dx.doi.org/10.1128/JVI.79.6.3401-3408.2005,PMC1075701,,,"Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel strain of coronavirus. Examination of the immune responses of patients who have recovered from SARS should provide important information for design of a safe and effective vaccine. We determined the continuous viral epitopes targeted by antibodies in plasma samples from convalescent SARS patients through biopanning with a vast M13 phage display dodecapeptide library. These epitopes converged to very short peptide fragments, one on each of the structural proteins spike and nucleocapsid and the nonstructural proteins 3a, 9b, and nsp 3. Immunoassays found that most of the patients who had recovered from SARS developed complementary antibodies to the epitope-rich region on the spike S2 protein, indicating that this is an immunodominant site on the viral envelope comprising the spike, matrix, and small envelope glycoproteins. These S2-targeting antibodies were shown to effectively neutralize the coronavirus, indicating that they provided protective immunity to help the patients recover from the viral infection. These results suggest that the SARS coronavirus might have an antigenic profile distinct from those of other human or animal coronaviruses. Due to the tested safety and protective effects of the convalescent-phase serological antibodies, identification of their complementary antigens may enable the design of an epitope-based vaccine to prevent potential antibody-mediated immunuopathology.",,"['Zhong, Xiaofen', 'Yang, Huanghao', 'Guo, Zu-Feng', 'Sin, Wan-Yee Fion', 'Chen, Wei', 'Xu, Junjie', 'Fu, Ling', 'Wu, Jie', 'Mak, Chun-Kit Gannon', 'Cheng, Chak-Sum Samuel', 'Yang, Yanzhen', 'Cao, Shuyong', 'Wong, Tin-Yau', 'Lai, Sik-To', 'Xie, Yong', 'Guo, Zhihong']",,,,
,PMC,Complementarity in the Supramolecular Design of Arenaviruses and Retroviruses Revealed by Electron Cryomicroscopy and Image Analysis,http://dx.doi.org/10.1128/JVI.79.6.3822-3830.2005,PMC1075687,,,"Arenaviruses are rodent-borne agents of diseases, including potentially lethal human hemorrhagic fevers. These enveloped viruses encapsidate a bisegmented ambisense single-stranded RNA genome that can be packaged in variable copy number. Electron cryomicroscopy and image analysis of New World Pichinde and Tacaribe arenaviruses and Old World lymphocytic choriomeningitis virus revealed pleomorphic enveloped particles ranging in diameter from ∼400 to ∼2,000 Å. The surface spikes were spaced ∼100 Å apart and extended ∼90 Å from the maximum phospholipid headgroup density of the outer bilayer leaflet. Distinctive stalk and head regions extended radially ∼30 and ∼60 Å from the outer bilayer leaflet, respectively. Two interior layers of density apposed to the inner leaflet of the viral lipid bilayer were assigned as protein Z and nucleoprotein (NP) molecules on the basis of their appearance, spacing, and projected volume. Analysis of en face views of virions lacking the GP-C spikes showed reflections consistent with paracrystalline packing of the NP molecules in a lattice with edges of ∼57 and ∼74 Å. The structural proteins of retroviruses and arenaviruses assemble with similar radial density distributions, using common cellular components.",,"['Neuman, Benjamin W.', 'Adair, Brian D.', 'Burns, John W.', 'Milligan, Ronald A.', 'Buchmeier, Michael J.', 'Yeager, Mark']",,,,
,PMC,Genetic Variability of Human Respiratory Coronavirus OC43,http://dx.doi.org/10.1128/JVI.79.5.3223-3225.2005,PMC548474,,,,,"['Vijgen, Leen', 'Lemey, Philippe', 'Keyaerts, Els', 'Ranst, Marc Van']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus 3a Protein Is a Viral Structural Protein,http://dx.doi.org/10.1128/JVI.79.5.3182-3186.2005,PMC548460,,,"The present study showed the association of a severe acute respiratory syndrome coronavirus (SCoV) accessory protein, 3a, with plasma membrane and intracellular SCoV particles in infected cells. 3a protein appeared to undergo posttranslational modifications in infected cells and was incorporated into SCoV particles, establishing that 3a protein was a SCoV structural protein.",,"['Ito, Naoto', 'Mossel, Eric C.', 'Narayanan, Krishna', 'Popov, Vsevolod L.', 'Huang, Cheng', 'Inoue, Taisuke', 'Peters, Clarence J.', 'Makino, Shinji']",,,,
,PMC,"Recombinant Mouse Hepatitis Virus Strain A59 from Cloned, Full-Length cDNA Replicates to High Titers In Vitro and Is Fully Pathogenic In Vivo",http://dx.doi.org/10.1128/JVI.79.5.3097-3106.2005,PMC548458,,,"Mouse hepatitis virus (MHV) is the prototype of group II coronaviruses and one of the most extensively studied coronaviruses. Here, we describe a reverse genetic system for MHV (strain A59) based upon the cloning of a full-length genomic cDNA in vaccinia virus. We show that the recombinant virus generated from cloned cDNA replicates to the same titers as the parental virus in cell culture (∼10(9) PFU/ml), has the same plaque morphology, and produces the same amounts and proportions of genomic and subgenomic mRNAs in virus-infected cells. In a mouse model of neurological infection, the recombinant and parental viruses are equally virulent, they replicate to the same titers in brain and liver, and they induce similar patterns of acute hepatitis, acute meningoencephalitis, and chronic demyelination. We also describe improvements in the use of the coronavirus reverse genetic system based on vaccinia virus cloning vectors. These modifications facilitate (i) the mutagenesis of cloned cDNA by using vaccinia virus-mediated homologous recombination and (ii) the rescue of recombinant coronaviruses by using a stable nucleocapsid protein-expressing cell line for the electroporation of infectious full-length genomes. Thus, our system represents a versatile and universal tool to study all aspects of MHV molecular biology and pathogenesis. We expect this system to provide valuable insights into the replication of group II coronaviruses that may lead to the development of novel strategies against coronavirus infections, including the related severe acute respiratory syndrome coronavirus.",,"['Coley, Scott E.', 'Lavi, Ehud', 'Sawicki, Stanley G.', 'Fu, Li', 'Schelle, Barbara', 'Karl, Nadja', 'Siddell, Stuart G.', 'Thiel, Volker']",,,,
,PMC,Cellular and Humoral Immunity following Snow Mountain Virus Challenge,http://dx.doi.org/10.1128/JVI.79.5.2900-2909.2005,PMC548455,,,"Little is known about the immune response to noroviruses. To elucidate the immunobiology of norovirus infection in humans, 15 volunteers were challenged with Snow Mountain virus (SMV), a genogroup 2 norovirus. We assessed the cellular and humoral immune response and infection by analyzing stool, serum, saliva, and peripheral blood mononuclear cell (PBMC) responses pre- and postchallenge. In contrast to Norwalk virus (NV), SMV infection was not dependent upon blood group secretor status. Nine of 15 volunteers were infected and showed a ≥4-fold increase over the prechallenge anti-SMV serum immunoglobulin G (IgG) titer, mostly subclass IgG1. Although serum IgG elicited by SMV infection was cross-reactive with Hawaii virus (HV), another genogroup 2 norovirus, salivary IgA was less cross-reactive. Neither SMV-elicited serum IgG nor salivary IgA cross-reacted with NV, a genogroup 1 norovirus. Significant increases in serum gamma interferon (IFN-γ) and IL-2, but not IL-6 or IL-10, were noted on day 2 postchallenge. For the majority of volunteers, both infected and uninfected, PBMCs stimulated with norovirus virus-like particles secreted IFN-γ and other Th1 cytokines, suggesting previous norovirus exposure in most volunteers. Like the IgG antibodies, the SMV-activated T cells were cross-reactive with HV but not NV. IFN-γ production was dependent upon CD4(+) cells, consistent with a predominant, but not exclusive, Th1 response. To our knowledge, this is the first report characterizing T-cell and cytokine responses following live norovirus challenge.",,"['Lindesmith, Lisa', 'Moe, Christine', 'LePendu, Jacques', 'Frelinger, Jeffrey A.', 'Treanor, John', 'Baric, Ralph S.']",,,,
,PMC,Recombinant Modified Vaccinia Virus Ankara Expressing the Spike Glycoprotein of Severe Acute Respiratory Syndrome Coronavirus Induces Protective Neutralizing Antibodies Primarily Targeting the Receptor Binding Region,http://dx.doi.org/10.1128/JVI.79.5.2678-2688.2005,PMC548443,,,"Immunization with a killed or inactivated viral vaccine provides significant protection in animals against challenge with certain corresponding pathogenic coronaviruses (CoVs). However, the promise of this approach in humans is hampered by serious concerns over the risk of leaking live severe acute respiratory syndrome (SARS) viruses. In this study, we generated a SARS vaccine candidate by using the live-attenuated modified vaccinia virus Ankara (MVA) as a vector. The full-length SARS-CoV envelope Spike (S) glycoprotein gene was introduced into the deletion III region of the MVA genome. The newly generated recombinant MVA, ADS-MVA, is replication incompetent in mammalian cells and highly immunogenic in terms of inducing potent neutralizing antibodies in mice, rabbits, and monkeys. After two intramuscular vaccinations with ADS-MVA alone, the 50% inhibitory concentration in serum was achieved with reciprocal sera dilutions of more than 1,000- to 10,000-fold in these animals. Using fragmented S genes as immunogens, we also mapped a neutralizing epitope in the region of N-terminal 400 to 600 amino acids of the S glycoprotein (S400-600), which overlaps with the angiotensin-converting enzyme 2 (ACE2) receptor-binding region (RBR; S318-510). Moreover, using a recombinant soluble RBR-Fc protein, we were able to absorb and remove the majority of the neutralizing antibodies despite observing that the full S protein tends to induce a broader spectrum of neutralizing activities in comparison with fragmented S proteins. Our data suggest that a major mechanism for neutralizing SARS-CoV likely occurs through blocking the interaction between virus and the cellular receptor ACE2. In addition, ADS-MVA induced potent immune responses which very likely protected Chinese rhesus monkeys from pathogenic SARS-CoV challenge.",,"['Chen, Zhiwei', 'Zhang, Linqi', 'Qin, Chuan', 'Ba, Lei', 'Yi, Christopher E.', 'Zhang, Fengwen', 'Wei, Qiang', 'He, Tian', 'Yu, Wenjie', 'Yu, Jian', 'Gao, Hong', 'Tu, Xinming', 'Gettie, Agegnehu', 'Farzan, Michael', 'Yuen, Kwok-yung', 'Ho, David D.']",,,,
,PMC,POXVIRUS TROPISM,http://dx.doi.org/10.1038/nrmicro1099,PMC4382915,,,"Despite the success of the WHO-led smallpox eradication programme a quarter of a century ago, there remains considerable fear that variola virus, or other related pathogenic poxviruses such as monkeypox, could re-emerge and spread disease in the human population. Even today, we are still mostly ignorant about why most poxvirus infections of vertebrate hosts show strict species specificity, or how zoonotic poxvirus infections occur when poxviruses occasionally leap into novel host species. Poxvirus tropism at the cellular level seems to be regulated by intracellular events downstream of virus binding and entry, rather than at the level of specific host receptors as is the case for many other viruses. This review summarizes our current understanding of poxvirus tropism and host range, and discusses the prospects of exploiting host-restricted poxvirus vectors for vaccines, gene therapy or tissue-targeted oncolytic viral therapies for the treatment of human cancers.",,"McFadden, Grant",,,,
,PMC,A differential proteome in tumors suppressed by an adenovirus-based skin patch vaccine encoding human carcinoembryonic antigen,http://dx.doi.org/10.1002/pmic.200401114,PMC3035721,,,"We created an anti-tumor vaccine by using adenovirus as a vector which contains a cytomegalovirus early promoter-directed human carcinoembryonic antigen gene (AdCMV-hCEA). In an attempt to develop the skin patch vaccine, we epicutaneously vaccinated Balb/c mice with AdCMV-hCPA. After nine weeks post-immunization, vaccinated mice evoked a robust antibody titer to CEA and demonstrated the capability of suppressing in vivo growth of implanted murine mammay adenocarioma cell line (JC-hCEA) tumor cells derived from a female Balb/c mouse. Proteomic analysis of the tumor masses in the non-vaccinated naïve and vaccinated mice reveal that six proteins change their abundance in the tumor mass. The levels of adenylate kinase 1, β-enolase, creatine kinase M chain, hemoglobin beta chain and prohibitin were statistically increased whereas the level of a creatine kinase fragment, which is undocumented, was decreased in the tumor of vaccinated mice. These proteins may provide a vital link between early-stage tumor suppression and immune response of skin patch vaccination.",,"['Huang, Chun-Ming', 'Shi, Zhongkai', 'DeSilva, Tivanka S.', 'Yamamoto, Masato', 'Van Kampen, Kent R.', 'Elmets, Craig A.', 'Tang, De-chu C.']",,,,
,PMC,Detection of CK20mRNA in peripheral blood of pancreatic cancer and its clinical significance,http://dx.doi.org/10.3748/wjg.v11.i7.1023,PMC4250764,,,"AIM: To detect the expression of CK20mRNA in peripheral blood of pancreatic cancer and evaluate its clinical significance. METHODS: Expression of CK20mRNA in peripheral blood was detected by fluorogenic qualitative reverse transcription-polymerase chain reaction (RT-PCR) in 40 cases of pancreatic cancer at the night before operation, in 5 cases of benign pancreatic diseases, in 5 cases of healthy individuals. The relationships were investigated between CK20mRNA expression and the clinicopathological variables, and clinical follow-up outcome in those patients with pancreatic cancer having undergone radical resection. RESULTS: Of the 40 patients with pancreatic cancer, 23 (57.5%) cases were positive for CK20mRNA expression. CK20mRNA expression was significantly correlated with lymphatic metastasis (P = 0.008), histopathological grading (P = 0.009), and pathological stage (P = 0.021); there was no significant correlation between CK20mRNA expression and age, gender, tumor diameter, and depth of invasion. The cumulative metastasis rates of patients with CK20mRNA expression were higher than those of patients with no CK20mRNA expression within 6 mo (34.7% vs 5.9%, P = 0.043) or 12 mo (73.9% vs 35.3%, P = 0.02) after operation. CK20mRNA expression in peripheral blood of pancreatic cancer indicated poorer prognosis. The survival rate of patients with CK20mRNA expression was lower than that of patients with negative CK20mRNA expression (Log-Rank = 13.31, P = 0.0003). CONCLUSION: CK20mRNA is a sensitive and specific molecular marker for the detection of micrometastasis in peripheral blood of patients with pancreatic cancer. The CK20mRNA expression in peripheral blood is correlated with biological characteristic of pancreatic cancer. It can help to predict the prognosis of pancreatic cancer after operation, and to determine which patient will benefit from aggressive adjuvant therapies.",,"['Zhang, Yun-Li', 'Feng, Jian-Guo', 'Gou, Jian-Min', 'Zhou, Li-Xin', 'Wang, Ping']",,,,
,PMC,The community-wide dilemma of hospital-acquired drug resistance,http://dx.doi.org/10.1073/pnas.0500088102,PMC549469,,,,,"Real, Leslie A.",,,,
,PMC,Proposed new International Health Regulations: Agreement must be reached to protect the global village from pandemic influenza,,PMC548715,,,,,"['Nicoll, Angus', 'Jones, Jane', 'Aavitsland, Preben', 'Giesecke, Johan']",,,,
,PMC,Quebec increases funding to fight infections in hospitals,,PMC548171,,,,,"Spurgeon, David",,,,
,PMC,Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human,http://dx.doi.org/10.1073/pnas.0409608102,PMC548959,,,"The genomic sequences of severe acute respiratory syndrome coronaviruses from human and palm civet of the 2003/2004 outbreak in the city of Guangzhou, China, were nearly identical. Phylogenetic analysis suggested an independent viral invasion from animal to human in this new episode. Combining all existing data but excluding singletons, we identified 202 single-nucleotide variations. Among them, 17 are polymorphic in palm civets only. The ratio of nonsynonymous/synonymous nucleotide substitution in palm civets collected 1 yr apart from different geographic locations is very high, suggesting a rapid evolving process of viral proteins in civet as well, much like their adaptation in the human host in the early 2002–2003 epidemic. Major genetic variations in some critical genes, particularly the Spike gene, seemed essential for the transition from animal-to-human transmission to human-to-human transmission, which eventually caused the first severe acute respiratory syndrome outbreak of 2002/2003.",,"['Song, Huai-Dong', 'Tu, Chang-Chun', 'Zhang, Guo-Wei', 'Wang, Sheng-Yue', 'Zheng, Kui', 'Lei, Lian-Cheng', 'Chen, Qiu-Xia', 'Gao, Yu-Wei', 'Zhou, Hui-Qiong', 'Xiang, Hua', 'Zheng, Hua-Jun', 'Chern, Shur-Wern Wang', 'Cheng, Feng', 'Pan, Chun-Ming', 'Xuan, Hua', 'Chen, Sai-Juan', 'Luo, Hui-Ming', 'Zhou, Duan-Hua', 'Liu, Yu-Fei', 'He, Jian-Feng', 'Qin, Peng-Zhe', 'Li, Ling-Hui', 'Ren, Yu-Qi', 'Liang, Wen-Jia', 'Yu, Ye-Dong', 'Anderson, Larry', 'Wang, Ming', 'Xu, Rui-Heng', 'Wu, Xin-Wei', 'Zheng, Huan-Ying', 'Chen, Jin-Ding', 'Liang, Guodong', 'Gao, Yang', 'Liao, Ming', 'Fang, Ling', 'Jiang, Li-Yun', 'Li, Hui', 'Chen, Fang', 'Di, Biao', 'He, Li-Juan', 'Lin, Jin-Yan', 'Tong, Suxiang', 'Kong, Xiangang', 'Du, Lin', 'Hao, Pei', 'Tang, Hua', 'Bernini, Andrea', 'Yu, Xiao-Jing', 'Spiga, Ottavia', 'Guo, Zong-Ming', 'Pan, Hai-Yan', 'He, Wei-Zhong', 'Manuguerra, Jean-Claude', 'Fontanet, Arnaud', 'Danchin, Antoine', 'Niccolai, Neri', 'Li, Yi-Xue', 'Wu, Chung-I', 'Zhao, Guo-Ping']",,,,
,PMC,The Transmembrane Oligomers of Coronavirus Protein E,http://dx.doi.org/10.1529/biophysj.104.051730,PMC1305130,,,"We have tested the hypothesis that severe acute respiratory syndrome (SARS) coronavirus protein E (SCoVE) and its homologs in other coronaviruses associate through their putative transmembrane domain to form homooligomeric α-helical bundles in vivo. For this purpose, we have analyzed the results of molecular dynamics simulations where all possible conformational and aggregational space was systematically explored. Two main assumptions were considered; the first is that protein E contains one transmembrane α-helical domain, with its N- and C-termini located in opposite faces of the lipid bilayer. The second is that protein E forms the same type of transmembrane oligomer and with identical backbone structure in different coronaviruses. The models arising from the molecular dynamics simulations were tested for evolutionary conservation using 13 coronavirus protein E homologous sequences. It is extremely unlikely that if any of our assumptions were not correct we would find a persistent structure for all the sequences tested. We show that a low energy dimeric, trimeric and two pentameric models appear to be conserved through evolution, and are therefore likely to be present in vivo. In support of this, we have observed only dimeric, trimeric, and pentameric aggregates for the synthetic transmembrane domain of SARS protein E in SDS. The models obtained point to residues essential for protein E oligomerization in the life cycle of the SARS virus, specifically N15. In addition, these results strongly support a general model where transmembrane domains transiently adopt many aggregation states necessary for function.",,"['Torres, Jaume', 'Wang, Jifeng', 'Parthasarathy, Krupakar', 'Liu, Ding Xiang']",,,,
,PMC,Human metapneumovirus,,PMC1463211,,,,,"Harnden, Anthony",,,,
,PMC,Elective and emergency surgery in patients with severe acute respiratory syndrome (SARS),,PMC3211568,,,,,"['Tien, Homer (Maj.) C.', 'Chughtai, Talat', 'Jogeklar, Amit', 'Cooper, Andrew B.', 'Brenneman, Frederick']",,,,
,PMC,Open tracheostomy in a suspect severe acute respiratory syndrome (SARS) patient: brief technical communication,,PMC3211558,,,,,"['Ahmed, Najma', 'Hare, Gregory M.T.', 'Merkley, Jane', 'Devlin, Roslyn', 'Baker, Andrew']",,,,
,PMC,Efficacy of a saponin-adjuvanted inactivated respiratory syncytial virus vaccine in calves,,PMC1082864,,,"The objective of this study was to determine whether a commercially available, saponin-adjuvanted, inactivated bovine respiratory syncytial virus (BRSV) vaccine would protect calves from experimental infection with virulent BRSV. This was a randomized controlled trial comprising 14, 8- to 9-week-old calves seronegative for BRSV. Group 1 calves (n = 8) were not vaccinated and group 2 calves (n = 6) were vaccinated on days 0 and 19 with an inactivated BRSV vaccine. All calves were challenged with virulent BRSV on day 46. Clinical signs, arterial PO(2), and immune responses were monitored after challenge. Calves were euthanatized on day 54 (8 d after challenge) and lungs were examined for lesions. Vaccination elicited increases in BRSV-specific immunoglobulin (Ig) G and virus neutralizing antibody titers. Challenge with BRSV resulted in severe respiratory tract disease and extensive pulmonary lesions in control calves, but no signs of clinical disease and minimal or no pulmonary lesions in vaccinated calves. Arterial blood oxygen values on day 53 (7 d after challenge) in control calves were significantly lower than those in vaccinated calves, which remained within normal limits. Control calves shed BRSV for several days after challenge, whereas BRSV was not detected on deep nasal swabs from vaccinated calves. In summary, the results indicated that this inactivated BRSV vaccine provided clinical protection from experimental infection with virulent virus 27 d after vaccination and significantly decreased the prevalence and severity of pulmonary lesions. Efficacy was similar to that reported for other commercial inactivated and modified-live BRSV vaccines.",,"['Ellis, John A.', 'West, Keith H.', 'Waldner, Cheryl', 'Rhodes, Carrie']",,,,
,PMC,Development and Validation of an Enzyme-Linked Immunosorbent Assay for Human Metapneumovirus Serology Based on a Recombinant Viral Protein,http://dx.doi.org/10.1128/CDLI.12.2.249-253.2005,PMC549303,,,"The human metapneumovirus (hMPV) is a newly reported respiratory virus belonging to the Paramyxoviridae family that has been associated with bronchiolitis and pneumonia in young children. We developed a simple enzyme-linked immunosorbent assay (ELISA) for hMPV serological testing using the nucleoprotein (N) from group A or B (N-A or N-B) as the antigen, and we evaluated it in both children and adults. The N proteins were first used in a Western immunoblot assay to identify hMPV-negative sera, which were then used to determine the cutoff value of the ELISA test. Subsequent evaluation of the ELISA-N test revealed that the mean reciprocal antibody titer of 20 randomly selected seropositive children was 143, compared to 69 for 20 seropositive adults. In a prospective evaluation of 71 adults with acute exacerbations of chronic obstructive pulmonary disease, 58 (81.6%) had prior hMPV antibodies and 3 (4.2%) had evidence of recent hMPV infection. In testing paired sera from adults (n = 4) with recent hMPV group A infection confirmed by reverse transcriptase PCR (RT-PCR), ELISAs using the N-A or N-B proteins were able to detect hMPV seroconversion. Moreover, testing of paired sera from three adults with a recent infection by the human respiratory syncytial virus confirmed by RT-PCR and serology did not reveal any increase in hMPV antibodies over time. The ELISA-N is a simple, objective, and specific serological test useful for detecting anti-hMPV antibodies following group A or B viral infections, which should permit a better understanding of the epidemiology of this virus.",,"['Hamelin, Marie-Ève', 'Boivin, Guy']",,,,
,PMC,Novel Immunofluorescence Assay Using Recombinant Nucleocapsid-Spike Fusion Protein as Antigen To Detect Antibodies against Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/CDLI.12.2.321-328.2005,PMC549298,,,"Severe acute respiratory syndrome (SARS) is caused by a novel and highly infectious virus named SARS coronavirus (SARS-CoV). Among the serological tests currently available for the detection of SARS-CoV, a whole-virus-based immunofluorescence assay (IFA) was considered one of the most sensitive assays and served as a “gold standard” during the SARS epidemic in Singapore in 2003. However, the need to manipulate live SARS-CoV in the traditional IFA limits its wide application due to the requirement for a biosafety level 3 laboratory and the risk of laboratory infection. Previously, we have identified two immunodominant epitopes, named N195 and Sc, in the two major structural proteins, the N and S proteins, of SARS-CoV (Q. He, K. H. Chong, H. H. Chng, B. Leung, A. E. Ling, T. Wei, S. W. Chan, E. E. Ooi, and J. Kwang, Clin. Diagn. Lab. Immunol., 11:417-422, 2004; L. Lu, I. Manopo, B. P. Leung, H. H. Chng, A. E. Ling, L. L. Chee, E. E. Ooi, S. W. Chan, and J. Kwang, J. Clin. Microbiol. 42:1570-1576, 2004). In the present study, the N195-Sc fusion protein was highly expressed in insect (Sf9) cells infected with a recombinant baculovirus bearing the hybrid gene under the control of a polyhedrin promoter. An IFA based on Sf9 cells producing the fusion protein was standardized with 23 serum samples from patients with SARS, 20 serum samples from patients with autoimmune diseases, and 43 serum samples from healthy blood donors. The detection rates were comparable to those obtained with a commercial SARS-CoV IFA kit (EUROIMMUN, Gross Groenau, Germany) and a conventional IFA performed at the Singapore General Hospital. Our data showed that the newly developed IFA could detect SARS-CoV in 22 of the 23 SARS-CoV-positive serum samples and gave no false-positive results when the sera from patients with autoimmune diseases and healthy individuals were tested. The detection rate was identical to those of the two whole-virus-based IFAs. Thus, the novel N-S fusion antigen-based IFA could be an attractive alternative to present whole-virus-based IFAs for the diagnosis of SARS-CoV infection.",,"['He, Qigai', 'Manopo, Ivanus', 'Lu, Liqun', 'Leung, Bernard P.', 'Chng, Hiok Hee', 'Ling, Ai Ee', 'Chee, Li Lian', 'Chan, Shzu-Wei', 'Ooi, Eng Eong', 'Sin, Yeo Lee', 'Ang, Brenda', 'Kwang, Jimmy']",,,,
,PMC,Scientists for a better world,http://dx.doi.org/10.1038/sj.embor.7400338,PMC1299248,,,"Science and technology could solve some of the developing world's most pressing problems. Individual scientists, by some modest efforts, could help as well.",,"Reynaud, Emmanuel G.",,,,
,PMC,Evaluation of a Multiplex Real-Time Reverse Transcriptase PCR Assay for Detection and Differentiation of Influenza Viruses A and B during the 2001-2002 Influenza Season in Israel,http://dx.doi.org/10.1128/JCM.43.2.589-595.2005,PMC548105,,,"The ability to rapidly diagnose influenza virus infections is of the utmost importance in the evaluation of patients with upper respiratory tract infections. It is also important for the influenza surveillance activities performed by national influenza centers. In the present study we modified a multiplex real-time reverse transcriptase PCR (RT-PCR) assay (which uses TaqMan chemistry) and evaluated it for its ability to detect and concomitantly differentiate influenza viruses A and B in 370 patient samples collected during the 2001-2002 influenza season in Israel. The performance of the TaqMan assay was compared to those of a multiplex one-step RT-PCR with gel detection, a shell vial immunofluorescence assay, and virus isolation in tissue culture. The TaqMan assay had an excellent sensitivity for the detection of influenza viruses compared to that of tissue culture. The overall sensitivity and specificity of the TaqMan assay compared to the results of culture were 98.4 and 85.5%, respectively. The sensitivity and specificity of the TaqMan assay for the detection of influenza virus A alone were 100 and 91.1%, respectively. On the other hand, the sensitivity and specificity for the detection of influenza virus B alone were 95.7 and 98.7%, respectively. The rapid turnaround time for the performance of the TaqMan assay (4.5 h) and the relatively low direct cost encourage the routine use of this assay in place of tissue culture. We conclude that the multiplex TaqMan assay is highly suitable for the rapid diagnosis of influenza virus infections both in well-established molecular biology laboratories and in reference clinical laboratories.",,"['Hindiyeh, Musa', 'Levy, Virginia', 'Azar, Roberto', 'Varsano, Noemi', 'Regev, Liora', 'Shalev, Yael', 'Grossman, Zehava', 'Mendelson, Ella']",,,,
,PMC,Detection of Severe Acute Respiratory Syndrome Coronavirus RNA in Plasma during the Course of Infection,http://dx.doi.org/10.1128/JCM.43.2.962-965.2005,PMC548103,,,"We examined severe acute respiratory syndrome-associated coronavirus (SARS-CoV) RNA in plasma of 32 patients (probable SARS cases) by a quantitative real-time reverse transcription-PCR assay and reported that the highest detection rate, 75%, was found between day 5 and day 7 of illness, followed by rates of 64, 50, and 38% found between day 8 and day 11, day 2 and day 4, and day 12 and day 16, respectively. Analysis of sequential SARS-CoV load in plasma from six cases revealed different patterns of viremia, with the peak between day 4 and day 8. Our findings of the high detection rate of SARS-CoV RNA in plasma before day 11, together with the relative convenience of collecting and handling plasma, suggest that plasma can be used for early diagnosis of SARS.",,"['Wang, Wei-Kung', 'Fang, Chi-Tai', 'Chen, Hui-Ling', 'Yang, Chao-Fu', 'Chen, Yee-Chun', 'Chen, Mei-Ling', 'Chen, Shey-Ying', 'Yang, Jyh-Yuan', 'Lin, Jih-Hui', 'Yang, Pan-Chyr', 'Chang, Shan-Chwen', None]",,,,
,PMC,Emergence of a Nephropathogenic Avian Infectious Bronchitis Virus with a Novel Genotype in India,http://dx.doi.org/10.1128/JCM.43.2.916-918.2005,PMC548090,,,We describe the emergence of a nephropathogenic avian infectious bronchitis virus (IBV) with a novel genotype in India. The Indian IBV isolate exhibited a relatively high degree of sequence divergence with reference strains. The highest homology was observed with strain 6/82 (68%) and the least homology with strain Mex/1765/99 (34.3%).,,"['Bayry, Jagadeesh', 'Goudar, Mallikarjun S.', 'Nighot, Prashant K.', 'Kshirsagar, Supriya G.', 'Ladman, Brian S.', 'Gelb, Jack', 'Ghalsasi, Govind R.', 'Kolte, Gopal N.']",,,,
,PMC,Self-Assembly of the Recombinant Capsid Protein of a Bovine Norovirus (BoNV) into Virus-Like Particles and Evaluation of Cross-Reactivity of BoNV with Human Noroviruses,http://dx.doi.org/10.1128/JCM.43.2.778-785.2005,PMC548067,,,"None of the enteric caliciviruses except Po/Sapo/GIII/Cowden/80/US replicates in cell culture, which complicates efforts to develop control strategies or to study viral replication. To develop serological assays for bovine noroviruses (BoNVs) and to determine the cross-reactivity of BoNV with human noroviruses, we generated two recombinant baculoviruses, rCV186-OH and rJNCV, to express the capsid genes of Bo/CV186-OH/00/US (Norovirus genogroup III [GIII], genotype 2 [GIII/2]). rCV186-OH expressed the expected 57-kDa capsid protein, but rJNCV expressed a truncated capsid protein of 35 kDa. Sequence analysis of rJNCV identified a single nucleotide deletion in the P domain of the capsid gene, which introduced a stop codon at amino acid 323. The recombinant capsid protein produced by rCV186-OH but not that produced by rJNCV self-assembled into virus-like particles (VLPs) similar to native BoNV. An antibody-capture enzyme-linked immunosorbent assay (ELISA) and antigen-capture ELISA (Ag-ELISA) detected serum antibody and antigen, respectively, from calves infected with Bo/CV186-OH/00/US but not antibodies or antigens to other enteric viruses. In other tests of the GIII/2 BoNV Ag-ELISA, no cross-reactivity was observed with VLPs from one GI and four GII human noroviruses and porcine sapovirus Cowden strain. Because, like human noroviruses, BoNVs do not grow in cell culture, the BoNV VLPs will be useful in the serological assays described for the detection of BoNV antibody and antigen. Consistent with the phylogenetic analysis of the capsid genes of bovine and human noroviruses (M. G. Han, J. R. Smiley, C. Thomas, and L. J. Saif, J. Clin. Microbiol. 42:5214-5224, 2004), the results suggest that GIII/2 BoNV does not share significant antigenic relationships with the five characterized human noroviruses tested.",,"['Han, M. G.', 'Wang, Q.', 'Smiley, J. R.', 'Chang, K. O.', 'Saif, L. J.']",,,,
,PMC,"The Pneumoplex Assays, a Multiplex PCR-Enzyme Hybridization Assay That Allows Simultaneous Detection of Five Organisms, Mycoplasma pneumoniae, Chlamydia (Chlamydophila) pneumoniae, Legionella pneumophila, Legionella micdadei, and Bordetella pertussis, and Its Real-Time Counterpart",http://dx.doi.org/10.1128/JCM.43.2.565-571.2005,PMC548062,,,"Respiratory disease caused by atypical bacteria remains an important cause of morbidity and mortality for adults and children, despite the widespread use of effective antimicrobials agents. Culture remains the “gold standard” for the detection of these agents. However, culture is labor-intensive, takes several days to weeks for growth, and can be very insensitive for the detection of some of these organisms. Newer singleplex PCR diagnostic tests are sensitive and specific, but multiple assays would be needed to detect all of the common pathogens. Therefore, we developed the Pneumoplex assays, a multiplex PCR-enzyme hybridization assay (the standard assay) and a multiplex real-time assay to detect the most common atypical pathogens in a single test. Primer and probe sequences were designed from conserved regions of specific genes for each of these organisms. The limits of detection were as follows: for Bordetella pertussis, 2 CFU/ml; for Legionella pneumophila (serotypes 1 to 15) and Legionella micdadei, 9 and 80 CFU/ml, respectively; for Mycoplasma pneumoniae, 5 CFU/ml; and for Chlamydia (Chlamydophila) pneumoniae, 0.01 50% tissue culture infective doses. Recombinant DNA controls for each of these organisms were constructed, and the number of copies for each DNA control was calculated. The Pneumoplex could detect each DNA control down to 10 copies/ml. The analytical specificity demonstrated no cross-reactivity between 23 common respiratory pathogens. One hundred twenty-five clinical bronchoalveolar lavage fluid samples tested by the standard assay demonstrated that the Pneumoplex yielded a sensitivity and a specificity of 100 and 98.5%, respectively. This test has the potential to assist clinicians in establishing a specific etiologic diagnosis before initiating therapy, to decrease hospital costs, and to prevent inappropriate antimicrobial therapy.",,"['Khanna, M.', 'Fan, J.', 'Pehler-Harrington, K.', 'Waters, C.', 'Douglass, P.', 'Stallock, J.', 'Kehl, S.', 'Henrickson, K. J.']",,,,
,PMC,Characterization of Virus Isolates by Particle-Associated Nucleic Acid PCR,http://dx.doi.org/10.1128/JCM.43.2.716-720.2005,PMC548055,,,"Diagnostic virus isolation is still frequently used, particularly from respiratory tract secretions. Testing positive virus cultures for all possible viruses is time-consuming, and unexpected or unknown viruses may escape detection. Therefore, a novel random PCR approach was developed that allows sequence-independent amplification of viral nucleic acids from virus isolation-positive cultures. Selectivity for viral sequences is obtained by preferential isolation of nucleic acids that are particle associated and resistant to nucleases. Using primers with a degenerated 3′ end, the isolated nucleic acids are amplified and the randomly amplified PCR products are cloned and sequenced. As proof of the concept, the PAN-PCR approach was applied to supernatants of coxsackievirus B3 and murine adenovirus type 1-infected cells. Enterovirus and adenovirus sequences were obtained, demonstrating that the random PCR approach allows detection of RNA and DNA viruses. As a first application of this PAN-PCR approach, we characterized a virus isolate from mouth-washing material of a patient with chronic fatigue syndrome and high antibody titers to coxsackievirus B2. The virus isolate had tested negative for enteroviruses and respiratory viruses (influenza viruses A and B, parainfluenza virus types 1 to 3, respiratory syncytial virus, and adenovirus) by immunofluorescence and PCR. Particle-associated, nuclease-resistant RNA and DNA were prepared from the supernatant of infected cells. The DNA and the reverse-transcribed RNA were randomly amplified, and PCR products were cloned and sequenced. Of 25 sequences obtained from the DNA preparation, 24 contained herpes simplex virus type 1 (HSV-1) sequences from 14 different loci spread over the HSV-1 genome. This result was confirmed by using a standard diagnostic HSV-PCR, demonstrating that the PAN-PCR correctly identified the virus isolate. Although the identification of HSV-1 in mouth-washing material is not surprising in retrospect, it clearly demonstrates the applicability of the PAN-PCR approach. This method should be particularly useful for characterizing virus isolates that have tested negative for all expected viruses and for identifying unknown viruses.",,"['Stang, Alexander', 'Korn, Klaus', 'Wildner, Oliver', 'Überla, Klaus']",,,,
,PMC,Identification of a Novel Coronavirus in Bats,http://dx.doi.org/10.1128/JVI.79.4.2001-2009.2005,PMC546586,,,"Exotic wildlife can act as reservoirs of diseases that are endemic in the area or can be the source of new emerging diseases through interspecies transmission. The recent emergence of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) highlights the importance of virus surveillance in wild animals. Here, we report the identification of a novel bat coronavirus through surveillance of coronaviruses in wildlife. Analyses of the RNA sequence from the ORF1b and S-gene regions indicated that the virus is a group 1 coronavirus. The virus was detected in fecal and respiratory samples from three bat species (Miniopterus spp.). In particular, 63% (12 of 19) of fecal samples from Miniopterus pusillus were positive for the virus. These findings suggest that this virus might be commonly circulating in M. pusillus in Hong Kong.",,"['Poon, L. L. M.', 'Chu, D. K. W.', 'Chan, K. H.', 'Wong, O. K.', 'Ellis, T. M.', 'Leung, Y. H. C.', 'Lau, S. K. P.', 'Woo, P. C. Y.', 'Suen, K. Y.', 'Yuen, K. Y.', 'Guan, Y.', 'Peiris, J. S. M.']",,,,
,PMC,Role of Nucleotides Immediately Flanking the Transcription-Regulating Sequence Core in Coronavirus Subgenomic mRNA Synthesis,http://dx.doi.org/10.1128/JVI.79.4.2506-2516.2005,PMC546574,,,"The generation of subgenomic mRNAs in coronavirus involves a discontinuous mechanism of transcription by which the common leader sequence, derived from the genome 5′ terminus, is fused to the 5′ end of the mRNA coding sequence (body). Transcription-regulating sequences (TRSs) precede each gene and include a conserved core sequence (CS) surrounded by relatively variable sequences (5′ TRS and 3′ TRS). Regulation of transcription in coronaviruses has been studied by reverse-genetics analysis of the sequences immediately flanking a unique CS in the Transmissible gastroenteritis virus genome (CS-S2), located inside the S gene, that does not lead to detectable amounts of the corresponding mRNA, in spite of its canonical sequence. The transcriptional inactivity of CS-S2 was genome position independent. The presence of a canonical CS was not sufficient to drive transcription, but subgenomic synthesis requires a minimum base pairing between the leader TRS (TRS-L) and the complement of the body TRS (cTRS-B) provided by the CS and its adjacent nucleotides. A good correlation was observed between the free energy of TRS-L and cTRS-B duplex formation and the levels of subgenomic mRNA S2, demonstrating that base pairing between the leader and body beyond the CS is a determinant regulation factor in coronavirus transcription. In TRS mutants with increasing complementarity between TRS-L and cTRS-B, a tendency to reach a plateau in ΔG values was observed, suggesting that a more precise definition of the TRS limits might be proposed, specifically that it consists of the central CS and around 4 nucleotides flanking 5′ and 3′ the CS. Sequences downstream of the CS exert a stronger influence on the template-switching decision according to a model of polymerase strand transfer and template switching during minus-strand synthesis.",,"['Sola, Isabel', 'Moreno, José L.', 'Zúñiga, Sonia', 'Alonso, Sara', 'Enjuanes, Luis']",,,,
,PMC,Civets Are Equally Susceptible to Experimental Infection by Two Different Severe Acute Respiratory Syndrome Coronavirus Isolates,http://dx.doi.org/10.1128/JVI.79.4.2620-2625.2005,PMC546564,,,"Severe acute respiratory syndrome (SARS) was caused by a novel virus now known as SARS coronavirus (SARS-CoV). The discovery of SARS-CoV-like viruses in masked palm civets (Paguma larvata) raises the possibility that civets play a role in SARS-CoV transmission. To test the susceptibility of civets to experimental infection by different SARS-CoV isolates, 10 civets were inoculated with two human isolates of SARS-CoV, BJ01 (with a 29-nucleotide deletion) and GZ01 (without the 29-nucleotide deletion). All inoculated animals displayed clinical symptoms, such as fever, lethargy, and loss of aggressiveness, and the infection was confirmed by virus isolation, detection of viral genomic RNA, and serum-neutralizing antibodies. Our data show that civets were equally susceptible to SARS-CoV isolates GZ01 and BJ01.",,"['Wu, Donglai', 'Tu, Changchun', 'Xin, Chaoan', 'Xuan, Hua', 'Meng, Qingwen', 'Liu, Yonggang', 'Yu, Yedong', 'Guan, Yuntao', 'Jiang, Yu', 'Yin, Xunnan', 'Crameri, Gary', 'Wang, Muping', 'Li, Changwen', 'Liu, Shengwang', 'Liao, Ming', 'Feng, Li', 'Xiang, Hua', 'Sun, Jinfu', 'Chen, Jinding', 'Sun, Yanwei', 'Gu, Shoulin', 'Liu, Nihong', 'Fu, Dexia', 'Eaton, Bryan T.', 'Wang, Lin-Fa', 'Kong, Xiangang']",,,,
,PMC,"Genomic and Bioinformatics Analysis of HAdV-4, a Human Adenovirus Causing Acute Respiratory Disease: Implications for Gene Therapy and Vaccine Vector Development",http://dx.doi.org/10.1128/JVI.79.4.2559-2572.2005,PMC546560,,,"Human adenovirus serotype 4 (HAdV-4) is a reemerging viral pathogenic agent implicated in epidemic outbreaks of acute respiratory disease (ARD). This report presents a genomic and bioinformatics analysis of the prototype 35,990-nucleotide genome (GenBank accession no. AY594253). Intriguingly, the genome analysis suggests a closer phylogenetic relationship with the chimpanzee adenoviruses (simian adenoviruses) rather than with other human adenoviruses, suggesting a recent origin of HAdV-4, and therefore species E, through a zoonotic event from chimpanzees to humans. Bioinformatics analysis also suggests a pre-zoonotic recombination event, as well, between species B-like and species C-like simian adenoviruses. These observations may have implications for the current interest in using chimpanzee adenoviruses in the development of vectors for human gene therapy and for DNA-based vaccines. Also, the reemergence, surveillance, and treatment of HAdV-4 as an ARD pathogen is an opportunity to demonstrate the use of genome determination as a tool for viral infectious disease characterization and epidemic outbreak surveillance: for example, rapid and accurate low-pass sequencing and analysis of the genome. In particular, this approach allows the rapid identification and development of unique probes for the differentiation of family, species, serotype, and strain (e.g., pathogen genome signatures) for monitoring epidemic outbreaks of ARD.",,"['Purkayastha, Anjan', 'Ditty, Susan E.', 'Su, Jing', 'McGraw, John', 'Hadfield, Ted L.', 'Tibbetts, Clark', 'Seto, Donald']",,,,
,PMC,Inhibition of Beta Interferon Induction by Severe Acute Respiratory Syndrome Coronavirus Suggests a Two-Step Model for Activation of Interferon Regulatory Factor 3,http://dx.doi.org/10.1128/JVI.79.4.2079-2086.2005,PMC546554,,,"Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus termed SARS-CoV. We and others have previously shown that the replication of SARS-CoV can be suppressed by exogenously added interferon (IFN), a cytokine which is normally synthesized by cells as a reaction to virus infection. Here, we demonstrate that SARS-CoV escapes IFN-mediated growth inhibition by preventing the induction of IFN-β. In SARS-CoV-infected cells, no endogenous IFN-β transcripts and no IFN-β promoter activity were detected. Nevertheless, the transcription factor interferon regulatory factor 3 (IRF-3), which is essential for IFN-β promoter activity, was transported from the cytoplasm to the nucleus early after infection with SARS-CoV. However, at a later time point in infection, IRF-3 was again localized in the cytoplasm. By contrast, IRF-3 remained in the nucleus of cells infected with the IFN-inducing control virus Bunyamwera delNSs. Other signs of IRF-3 activation such as hyperphosphorylation, homodimer formation, and recruitment of the coactivator CREB-binding protein (CBP) were found late after infection with the control virus but not with SARS-CoV. Our data suggest that nuclear transport of IRF-3 is an immediate-early reaction to virus infection and may precede its hyperphosphorylation, homodimer formation, and binding to CBP. In order to escape activation of the IFN system, SARS-CoV appears to block a step after the early nuclear transport of IRF-3.",,"['Spiegel, Martin', 'Pichlmair, Andreas', 'Martínez-Sobrido, Luis', 'Cros, Jerome', 'García-Sastre, Adolfo', 'Haller, Otto', 'Weber, Friedemann']",,,,
,PMC,Molecular and Biological Characterization of Human Monoclonal Antibodies Binding to the Spike and Nucleocapsid Proteins of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.79.3.1635-1644.2005,PMC544131,,,"Human monoclonal antibodies (MAbs) were selected from semisynthetic antibody phage display libraries by using whole irradiated severe acute respiratory syndrome (SARS) coronavirus (CoV) virions as target. We identified eight human MAbs binding to virus and infected cells, six of which could be mapped to two SARS-CoV structural proteins: the nucleocapsid (N) and spike (S) proteins. Two MAbs reacted with N protein. One of the N protein MAbs recognized a linear epitope conserved between all published human and animal SARS-CoV isolates, and the other bound to a nonlinear N epitope. These two N MAbs did not compete for binding to SARS-CoV. Four MAbs reacted with the S glycoprotein, and three of these MAbs neutralized SARS-CoV in vitro. All three neutralizing anti-S MAbs bound a recombinant S1 fragment comprising residues 318 to 510, a region previously identified as the SARS-CoV S receptor binding domain; the nonneutralizing MAb did not. Two strongly neutralizing anti-S1 MAbs blocked the binding of a recombinant S fragment (residues 1 to 565) to SARS-CoV-susceptible Vero cells completely, whereas a poorly neutralizing S1 MAb blocked binding only partially. The MAb ability to block S1-receptor binding and the level of neutralization of the two strongly neutralizing S1 MAbs correlated with the binding affinity to the S1 domain. Finally, epitope mapping, using recombinant S fragments (residues 318 to 510) containing naturally occurring mutations, revealed the importance of residue N479 for the binding of the most potent neutralizing MAb, CR3014. The complete set of SARS-CoV MAbs described here may be useful for diagnosis, chemoprophylaxis, and therapy of SARS-CoV infection and disease.",,"['van den Brink, Edward N.', 'ter Meulen, Jan', 'Cox, Freek', 'Jongeneelen, Mandy A. C.', 'Thijsse, Alexandra', 'Throsby, Mark', 'Marissen, Wilfred E.', 'Rood, Pauline M. L.', 'Bakker, Alexander B. H.', 'Gelderblom, Hans R.', 'Martina, Byron E.', 'Osterhaus, Albert D. M. E.', 'Preiser, Wolfgang', 'Doerr, Hans Wilhelm', 'de Kruif, John', 'Goudsmit, Jaap']",,,,
,PMC,Identification of Two Neutralizing Regions on the Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Produced from the Mammalian Expression System,http://dx.doi.org/10.1128/JVI.79.3.1906-1910.2005,PMC544123,,,"The Spike (S) protein of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) plays important roles in viral pathogenesis and potentially in the development of an effective vaccine against this virulent infectious disease. In this study, the codon-optimized S gene of SARS-CoV was synthesized to construct DNA vaccine plasmids expressing either the full-length or segments of the S protein. High titer S-specific immunoglobulin G antibody responses were elicited in rabbits immunized with DNA against various segments of the S protein. Two neutralizing domains were identified on the S protein, one at the N terminus (Ser12-Thr535) and the other near the C terminus (Arg797-Ile1192).",,"['Wang, Shixia', 'Chou, Te-hui W.', 'Sakhatskyy, Pavlo V.', 'Huang, Song', 'Lawrence, John M.', 'Cao, Hong', 'Huang, Xiaoyun', 'Lu, Shan']",,,,
,PMC,Identification of the Membrane-Active Regions of the Severe Acute Respiratory Syndrome Coronavirus Spike Membrane Glycoprotein Using a 16/18-Mer Peptide Scan: Implications for the Viral Fusion Mechanism,http://dx.doi.org/10.1128/JVI.79.3.1743-1752.2005,PMC544113,,,"We have identified the membrane-active regions of the severe acute respiratory syndrome coronavirus (SARS CoV) spike glycoprotein by determining the effect on model membrane integrity of a 16/18-mer SARS CoV spike glycoprotein peptide library. By monitoring the effect of this peptide library on membrane leakage in model membranes, we have identified three regions on the SARS CoV spike glycoprotein with membrane-interacting capabilities: region 1, located immediately upstream of heptad repeat 1 (HR1) and suggested to be the fusion peptide; region 2, located between HR1 and HR2, which would be analogous to the loop domain of human immunodeficiency virus type 1; and region 3, which would correspond to the pretransmembrane region. The identification of these membrane-active regions, which are capable of modifying the biophysical properties of phospholipid membranes, supports their direct role in SARS CoV-mediated membrane fusion, as well as facilitating the future development of SARS CoV entry inhibitors.",,"['Guillén, Jaime', 'Pérez-Berná, Ana J.', 'Moreno, Miguel R.', 'Villalaín, José']",,,,
,PMC,Complete Genomic Sequence of Human Coronavirus OC43: Molecular Clock Analysis Suggests a Relatively Recent Zoonotic Coronavirus Transmission Event,http://dx.doi.org/10.1128/JVI.79.3.1595-1604.2005,PMC544107,,,"Coronaviruses are enveloped, positive-stranded RNA viruses with a genome of approximately 30 kb. Based on genetic similarities, coronaviruses are classified into three groups. Two group 2 coronaviruses, human coronavirus OC43 (HCoV-OC43) and bovine coronavirus (BCoV), show remarkable antigenic and genetic similarities. In this study, we report the first complete genome sequence (30,738 nucleotides) of the prototype HCoV-OC43 strain (ATCC VR759). Complete genome and open reading frame (ORF) analyses were performed in comparison to the BCoV genome. In the region between the spike and membrane protein genes, a 290-nucleotide deletion is present, corresponding to the absence of BCoV ORFs ns4.9 and ns4.8. Nucleotide and amino acid similarity percentages were determined for the major HCoV-OC43 ORFs and for those of other group 2 coronaviruses. The highest degree of similarity is demonstrated between HCoV-OC43 and BCoV in all ORFs with the exception of the E gene. Molecular clock analysis of the spike gene sequences of BCoV and HCoV-OC43 suggests a relatively recent zoonotic transmission event and dates their most recent common ancestor to around 1890. An evolutionary rate in the order of 4 × 10(−4) nucleotide changes per site per year was estimated. This is the first animal-human zoonotic pair of coronaviruses that can be analyzed in order to gain insights into the processes of adaptation of a nonhuman coronavirus to a human host, which is important for understanding the interspecies transmission events that led to the origin of the severe acute respiratory syndrome outbreak.",,"['Vijgen, Leen', 'Keyaerts, Els', 'Moës, Elien', 'Thoelen, Inge', 'Wollants, Elke', 'Lemey, Philippe', 'Vandamme, Anne-Mieke', 'Van Ranst, Marc']",,,,
,PMC,Nitric Oxide Inhibits the Replication Cycle of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.79.3.1966-1969.2005,PMC544093,,,"Nitric oxide (NO) is an important signaling molecule between cells which has been shown to have an inhibitory effect on some virus infections. The purpose of this study was to examine whether NO inhibits the replication cycle of the severe acute respiratory syndrome coronavirus (SARS CoV) in vitro. We found that an organic NO donor, S-nitroso-N-acetylpenicillamine, significantly inhibited the replication cycle of SARS CoV in a concentration-dependent manner. We also show here that NO inhibits viral protein and RNA synthesis. Furthermore, we demonstrate that NO generated by inducible nitric oxide synthase, an enzyme that produces NO, inhibits the SARS CoV replication cycle.",,"['Åkerström, Sara', 'Mousavi-Jazi, Mehrdad', 'Klingström, Jonas', 'Leijon, Mikael', 'Lundkvist, Åke', 'Mirazimi, Ali']",,,,
,PMC,Mutual Interference between Genomic RNA Replication and Subgenomic mRNA Transcription in Brome Mosaic Virus,http://dx.doi.org/10.1128/JVI.79.3.1438-1451.2005,PMC544081,,,"Replication by many positive-strand RNA viruses includes genomic RNA amplification and subgenomic mRNA (sgRNA) transcription. For brome mosaic virus (BMV), both processes occur in virus-induced, membrane-associated compartments, require BMV replication factors 1a and 2a, and use negative-strand RNA3 as a template for genomic RNA3 and sgRNA syntheses. To begin elucidating their relations, we examined the interaction of RNA3 replication and sgRNA transcription in Saccharomyces cerevisiae expressing 1a and 2a, which support the full RNA3 replication cycle. Blocking sgRNA transcription stimulated RNA3 replication by up to 350%, implying that sgRNA transcription inhibits RNA3 replication. Such inhibition was independent of the sgRNA-encoded coat protein and operated in cis. We further found that sgRNA transcription inhibited RNA3 replication at a step or steps after negative-strand RNA3 synthesis, implying competition with positive-strand RNA3 synthesis for negative-strand RNA3 templates, viral replication factors, or common host components. Consistent with this, sgRNA transcription was stimulated by up to 400% when mutations inhibiting positive-strand RNA3 synthesis were introduced into the RNA3 5′-untranslated region. Thus, BMV subgenomic and genomic RNA syntheses mutually interfered with each other, apparently by competition for one or more common factors. In plant protoplasts replicating all three BMV genomic RNAs, mutations blocking sgRNA transcription often had lesser effects on RNA3 accumulation, possibly because RNA3 also competed with RNA1 and RNA2 replication templates and because any increase in RNA3 replication at the expense of RNA1 and RNA2 would be self-limited by decreased 1a and 2a expression from RNA1 and RNA2.",,"['Grdzelishvili, Valery Z.', 'Garcia-Ruiz, Hernan', 'Watanabe, Tokiko', 'Ahlquist, Paul']",,,,
,PMC,Avian Flu – A Bird's Eye View,http://dx.doi.org/10.1016/S0377-1237(05)80016-4,PMC4922980,,,"Influenza A (H5N1) virus infects a variety of animals, birds and humans. Present ongoing epidemic of this deadly virus in poultry livestock and humans has had major economic and health repercussions. It causes a wide spectrum of clinical features in human beings ranging from mild respiratory tract infection to a fatal pneumonia leading to multi organ system failure. Diagnosis is mainly clinical, aided by lab features like lymphopaenia and non-specific chest X-ray findings. Diagnostic tests are being evolved for rapid and specific diagnosis. Management is mainly symptomatic. Newer and effective antivirals, i.e. amantadine, zanamivir etc are also being tried.",,"['Mehta, SR', 'Singh, VP', 'Kumar, Suman', 'Kapoor, Rajan', 'Ananthakrishnan, R']",,,,
,PMC,Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses,http://dx.doi.org/10.1073/pnas.0409065102,PMC545557,,,"Molecular characterization of the severe acute respiratory syndrome coronavirus has revealed genetic diversity among isolates. The spike (S) glycoprotein, the major target for vaccine and immune therapy, shows up to 17 substitutions in its 1,255-aa sequence; however, the biologic significance of these changes is unknown. Here, the functional effects of S mutations have been determined by analyzing their affinity for a viral receptor, human angiotensin-converting enzyme 2 (hACE-2), and their sensitivity to Ab neutralization with viral pseudotypes. Although minor differences among eight strains transmitted during human outbreaks in early 2003 were found, substantial functional changes were detected in S derived from a case in late 2003 from Guangdong province [S(GD03T0013)] and from two palm civets, S(SZ3) and S(SZ16). S(GD03T0013) depended less on the hACE-2 receptor and was markedly resistant to Ab inhibition. Unexpectedly, Abs that neutralized most human S glycoproteins enhanced entry mediated by the civet virus S glycoproteins. The mechanism of enhancement involved the interaction of Abs with conformational epitopes in the hACE-2-binding domain. Finally, improved immunogens and mAbs that minimize this complication have been defined. These data show that the entry of severe acute respiratory syndrome coronaviruses can be enhanced by Abs, and they underscore the need to address the evolving diversity of this newly emerged virus for vaccines and immune therapies.",,"['Yang, Zhi-yong', 'Werner, Heidi C.', 'Kong, Wing-pui', 'Leung, Kwanyee', 'Traggiai, Elisabetta', 'Lanzavecchia, Antonio', 'Nabel, Gary J.']",,,,
,PMC,"Expanding Access to Antiretroviral Therapy in Sub-Saharan Africa: Avoiding the Pitfalls and Dangers, Capitalizing on the Opportunities",http://dx.doi.org/10.2105/AJPH.2004.040121,PMC1449845,,,"We describe a number of pitfalls that may occur with the push to rapidly expand access to antiretroviral therapy in sub-Saharan Africa. These include undesirable opportunity costs, the fragmentation of health systems, worsening health care inequities, and poor and unsustained treatment outcomes. On the other hand, AIDS “treatment activism” provides an opportunity to catalyze comprehensive health systems development and reduce health care inequities. However, these positive benefits will only happen if we explicitly set out to achieve them. We call for a greater commitment toward health activism that tackles the broader political and economic constraints to human and health systems development in Africa, as well as toward the resuscitation of inclusive and equitable public health systems.",,"['McCoy, David', 'Chopra, Mickey', 'Loewenson, Rene', 'Aitken, Jean-Marion', 'Ngulube, Thabale', 'Muula, Adamson', 'Ray, Sunanda', 'Kureyi, Tendayi', 'Ijumba, Petrida', 'Rowson, Mike']",,,,
,PMC,Application of Graphical Relational Representation Techniques in Healthcare Website : Taking SARS Website Information Query and Representaion as an Example,,PMC1560848,,,,,"['Hsu, Chia-Jung', 'Lu, Chia-Lien', 'Chen, Wen-Chih', 'Chang, Polun']",,,,
,PMC,How to approach major surgery where patients refuse blood transfusion (including Jehovah's Witnesses).,http://dx.doi.org/10.1308/1478708051414,PMC1963852,,,"Jehovah's Witnesses do not permit the use of allogeneic blood products. An increasing number of patients are refusing blood transfusion for non-religious reasons. In addition, blood stores are decreasing, and costs are increasing. Transfusion avoidance strategies are, therefore, desirable. Bloodless surgery refers to the co-ordinated peri-operative care of patients aiming to avoid blood transfusion, and improve patient outcomes. These principles are likely to gain popularity, and become standard practice for all patients. This review offers a practical approach to the surgical management of Jehovah's Witnesses, and an introduction to the principles of bloodless surgery that can be applied to the management of all patients.",,"['Gohel, M. S.', 'Bulbulia, R. A.', 'Slim, F. J.', 'Poskitt, K. R.', 'Whyman, M. R.']",,,,
,PMC,SARS: Lessons To Learn For GPs When Handling A Public Health Crisis,,PMC1266255,,,,,"['Wong, William CW', 'Wong, Samuel YS', 'Jaakkimainen, Liisa', 'Bondy, Susan', 'Tsang, Kwong KA', 'Lee, Albert']",,,,
,PMC,Sexually transmitted infections,,PMC2095008,,,,,"Nicolle, LE",,,,
,PMC,The Financial Impact of Controlling a Respiratory Virus Outbreak in a Teaching Hospital: Lessons Learned from SARS,http://dx.doi.org/10.1007/BF03404018,PMC6975983,,,"BACKGROUND: Outbreaks of Severe Acute Respiratory Syndrome (SARS) in 2003 and renewed concerns regarding pandemic influenza have resulted in widespread planning for future respiratory disease outbreaks. Such planning should include accurate cost estimates for any proposed disease control strategies. From the acute care hospital perspective, such estimates typically take into account the cost of supplies and equipment, but rarely consider indirect costs such as lost revenue due to the scaling down of programs. METHODS: Retrospective cost analysis. Costs and savings were calculated from the hospital perspective using financial records. Costs were categorized to determine the major areas of expenditure and savings. RESULTS: We report that controlling a SARS outbreak in a teaching hospital over an 8-week period cost $12 million Canadian. Lost revenue and labour accounted for two thirds of the costs incurred while excess spending on services, materials, supplies and renovation of existing space accounted for the remaining one third. CONCLUSIONS: Cost estimates that consider only excess expenditures may considerably underestimate the true cost of infection control strategies.",,"['Achonu, Camille', 'Laporte, Audrey', 'Gardam, Michael A.']",,,,
,PMC,Prevalence of Giardia and Cryptosporidium in beef cows in southern Ontario and in beef calves in southern British Columbia,,PMC1082856,,,"In 1998 and 1999, fecal samples were collected from 669 beef cows on 39 farms located within 10 counties of Ontario. Overall prevalences of Giardia, Cryptosporidium muris, and Cryptosporidium parvum in cows were 8.7%, 10.6%, and 18.4%, respectively. Of the 39 farms sampled, Giardia was detected on 64%, Cr. muris on 72%, and Cr. parvum on 90%. Cryptosporidium parvum was detected in 28% of the cows in 1998 and in 5.2% in 1999. Differences between the 2 y were attributed to sampling during calving in 1998 and during gestation in 1999. In 1998, Giardia, Cr. muris, and Cr. parvum were detected in herds provided with municipal water. In 1998, 193 calves were sampled from 10 farms, representing 4 watersheds, in British Columbia. Thirty-six percent of the calves exhibited signs of diarrhea. Overall prevalences of Giardia and Cryptosporidium spp. in calves were 36% and 13%, respectively. There was evidence that calves with Giardia were more likely to develop scours. Restricting cattle from surface water during periods of high shedding may reduce watershed contamination.",,"['McAllister, Tim A.', 'Olson, Merle E.', 'Fletch, Andy', 'Wetzstein, Merv', 'Entz, Toby']",,,,
,PMC,Monoclonal Antibody-Based Antigen Capture Enzyme-Linked Immunosorbent Assay Reveals High Sensitivity of the Nucleocapsid Protein in Acute-Phase Sera of Severe Acute Respiratory Syndrome Patients,http://dx.doi.org/10.1128/CDLI.12.1.135-140.2005,PMC540218,,,"Accurate and timely diagnosis of severe acute respiratory syndrome coronavirus (SARS-CoV) infection is a critical step in preventing another global outbreak. In this study, 829 serum specimens were collected from 643 patients initially reported to be infected with SARS-CoV. The sera were tested for the N protein of SARS-CoV by using an antigen capture enzyme-linked immunosorbent assay (ELISA) based on monoclonal antibodies against the N protein of SARS-CoV and compared to 197 control serum samples from healthy donors and non-SARS febrile patients. The results of the N protein detection analysis were directly related to the serological analysis data. From 27 SARS patients who tested positive with the neutralization test, 100% of the 24 sera collected from 1 to 10 days after the onset of symptoms were positive for the N protein. N protein was not detected beyond day 11 in this group. The positive rates of N protein for sera collected at 1 to 5, 6 to 10, 11 to 15, and 16 to 20 days after the onset of symptoms for 414 samples from 298 serologically confirmed patients were 92.9, 69.8, 36.4, and 21.1%, respectively. For 294 sera from 248 serological test-negative patients, the rates were 25.6, 16.7, 9.3, and 0%, respectively. The N protein was not detected in 66 patients with cases of what was initially suspected to be SARS but serologically proven to be negative for SARS and in 197 serum samples from healthy donors and non-SARS febrile patients. The specificity of the assay was 100%. Furthermore, of 16 sera collected from four patients during the SARS recurrence in Guangzhou, 5 sera collected from 7 to 9 days after the onset of symptoms were positive for the N protein. N protein detection exhibited a high positive rate, 96 to 100%, between day 3 and day 5 after the onset of symptoms for 27 neutralization test-positive SARS patients and 298 serologically confirmed patients. The N protein detection rate continually decreased beginning with day 10, and N protein was not detected beyond day 19 after the onset of symptoms. In conclusion, an antigen capture ELISA reveals a high N protein detection rate in acute-phase sera of patients with SARS, which makes it useful for early diagnosis of SARS.",,"['Di, Biao', 'Hao, Wei', 'Gao, Yang', 'Wang, Ming', 'Wang, Ya-di', 'Qiu, Li-wen', 'Wen, Kun', 'Zhou, Duan-hua', 'Wu, Xin-wei', 'Lu, En-jie', 'Liao, Zhi-yong', 'Mei, Ya-bo', 'Zheng, Bo-jian', 'Che, Xiao-yan']",,,,
,PMC,"Acquired but reversible loss of erythrocyte complement receptor 1 (CR1, CD35) and its longitudinal alteration in patients with severe acute respiratory syndrome",http://dx.doi.org/10.1111/j.1365-2249.2005.02681.x,PMC1809271,,,"This longitudinal study investigates the change of erythrocyte complement receptor (E-CR1) expression in patients with severe acute respiratory syndrome (SARS). Circulating E-CR1 expression was semiquantified by flow cytometric analyses in 54 SARS patients and in 212 healthy individuals as a control. Since E-CR1 expression is influenced by the genetic polymorphisms in the CR1 gene, a major genetic polymorphism located within intron 27 of the CR1 gene was simultaneously analysed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The results showed that the expression level of E-CR1 (referred to as net fluorescence intensity values, NFI) was statistically correlated with the relevant genetic genotypes among the Chinese population including the healthy individuals (NFI: 5·14 ± 0·82, 3·57 ± 0·66 and 2·67 ± 0·32 for HH, HL and LL genotypes, respectively) and SARS patients (NFI: 3·52 ± 0·91 and 2·63 ± 0·70 for HH and HL genotypes, respectively). Interestingly, the expression density of E-CR1 was found to fall significantly during the initiation and progressive phases (weeks 1 and 2 after the disease onset) and gradually returned close to normal through their whole convalescent phase (beginning from weeks 2 or 3 to weeks 7 or 8) in SARS patients irrespective CR1 genotype. In conclusion, our findings, at least, suggest that E-CR1 is likely involved in immune pathogenesis of SARS disease.",,"['Wang, F S', 'Chu, F L', 'Jin, L', 'Li, Y G', 'Zhang, Z', 'Xu, D', 'Shi, M', 'Wu, H', 'Moulds, J-M']",,,,
,PMC,The Role of Bystander T Cells in CNS Pathology and Pathogen Clearance,,PMC5292138,,,"It is generally accepted that both self- and pathogen-specific T lymphocytes have the potential to mediate immunopathogenesis and contribute to a variety of human ailments. Despite this unfortunate tendency to induce tissue injury, these cells are guided by interactions with peptide-loaded major histocompatibility complexes (MHC) and adhere appropriately to a vital evolutionary constraint imposed by the host: specificity. More recently, a series of studies have demonstrated that bystander T cells of an irrelevant specificity can bypass peptide/MHC restriction and become active participants in immunopathology. This review critically evaluates the role of bystander T cells in immunopathogenesis and pathogen clearance in the periphery as well as the central nervous system and attempts to establish the likelihood of their participation in human disease.",,"McGavern, Dorian B.",,,,
,PMC,"SARS, Mars and chocolate bars",http://dx.doi.org/10.1038/sj.embor.7400326,PMC1299236,,,,,"Gannon, Frank",,,,
,PMC,Pushing and pulling,http://dx.doi.org/10.1038/sj.embor.7400320,PMC1299230,,,,,"Kaplan, Warren A.",,,,
,PMC,Enhanced viral clearance in interleukin-18 gene-deficient mice after pulmonary infection with influenza A virus,http://dx.doi.org/10.1111/j.1365-2567.2004.02000.x,PMC1782065,,,"T helper 1 driven immune responses facilitate host defence during viral infections. Because interleukin-18 (IL-18) mediates T helper 1 driven immune responses, and since mature IL-18 is up-regulated in human macrophages after influenza virus infection in vitro, it has been suggested that IL-18 plays an important role in the immune response to influenza. To determine the role of IL-18 in respiratory tract infection with influenza, IL-18 gene-deficient (IL-18(–/–)) and normal wildtype mice were intranasally inoculated with influenza A virus. Influenza resulted in an increase in constitutively expressed IL-18 in the lungs of wildtype mice. The clearance of influenza A was inhibited by IL-18, as indicated by reduced viral loads on day 8 and day 12 after infection in IL-18(–/–) mice. This enhanced viral clearance correlated with increased CD4(+) T-cell activation in the lungs as reflected by CD69 expression on the cell surface. Surprisingly, interferon-γ (IFN-γ) levels were similar in the lungs of IL-18(–/–) mice and wildtype mice. Intracellular IFN-γ staining revealed similar expression levels in lung-derived natural killer cells, CD4(+) and CD8(+) T cells, indicating that IFN-γ production is IL-18-independent during influenza virus infection. Tumour necrosis factor-α production by CD4(+) T cells was significantly lower in IL-18(–/–) mice than in wildtype mice. Our data indicate that endogenous IL-18 impairs viral clearance during influenza A infection.",,"['Van Der Sluijs, Koenraad F', 'Van Elden, Leontine J R', 'Arens, Ramon', 'Nijhuis, Monique', 'Schuurman, Rob', 'Florquin, Sandrine', 'Kwakkel, Joan', 'Akira, Shizuo', 'Jansen, Henk M', 'Lutter, René', 'Van Der Polls, Tom']",,,,
,PMC,Detection of Human Influenza A Viruses by Loop-Mediated Isothermal Amplification,http://dx.doi.org/10.1128/JCM.43.1.427-430.2005,PMC540134,,,"Here we describe the use of the loop-mediated isothermal amplification (LAMP) method to detect human influenza viruses (H1 to H3). Our results were correlated 100% with results deduced from routine clinical diagnostic tests. In addition, we also developed a LAMP assay specific for human β-actin cDNA as a quality control test.",,"['Poon, Leo L. M.', 'Leung, Cynthia S. W.', 'Chan, Kwok H.', 'Lee, Jack H. C.', 'Yuen, Kwok Y.', 'Guan, Yi', 'Peiris, Joseph S. M.']",,,,
,PMC,High Prevalence of Respiratory Viral Infections in Patients Hospitalized in an Intensive Care Unit for Acute Respiratory Infections as Detected by Nucleic Acid-Based Assays,http://dx.doi.org/10.1128/JCM.43.1.455-457.2005,PMC540110,,,"Forty-seven bronchoalveolar lavages (BAL) were obtained from 41 patients with acute pneumonia attending an intensive care unit. By molecular diagnosis, 30% of total BAL and 63% of bacteria-negative BAL were positive for respiratory viruses. Molecular detection allows for high-rate detection of respiratory viral infections in adult patients suffering from severe pneumonia.",,"['Legoff, Jérôme', 'Guérot, Emmanuel', 'Ndjoyi-Mbiguino, Angélique', 'Matta, Mathieu', 'Si-Mohamed, Ali', 'Gutmann, Laurent', 'Fagon, Jean-Yves', 'Bélec, Laurent']",,,,
,PMC,"Proceedings, 104th Annual Meeting Medical Library Association, Inc., Washington, DC, May 21–26, 2004",,PMC545145,,,,,"['Fulda, Pauline O.', 'Satterthwaite, Rebecca K.']",,,,
,PMC,Constructing a concise medical taxonomy,,PMC545132,,,,,"McGregor, Bruce",,,,
,PMC,"Research Gaps in Protecting Healthcare Workers From SARS and Other Respiratory Pathogens: An Interdisciplinary, Multi-Stakeholder, Evidence-Based Approach",,PMC4880470,,,"OBJECTIVE: To identify priorities for further research in protecting healthcare workers (HCWs) from severe acute respiratory syndrome (SARS) and other respiratory pathogens by summarizing the basic science of infectious bioaerosols and the efficacy of facial protective equipment; the organizational, environmental, and individual factors that influence the success of infection control and occupational health programs; and factors identified by HCWs as important. METHOD: An extensive literature review was conducted and 15 focus groups held, mostly with frontline HCWs in Toronto. Critical gaps in knowledge were identified and prioritized. RESULTS: Highest priority was given to organizational factors that create a climate of safety. Other priority areas included understanding aerosolization risks and practical measures to control bioaerosols at the source. CONCLUSIONS: Further research is warranted to improve safety climate in health care and, specifically, to provide greater protection against respiratory pathogens.",,"['Yassi, Annalee', 'Moore, David', 'FitzGerald, J. Mark', 'Bigelow, Philip', 'Hon, Chun-Yip', 'Bryce, Elizabeth', None]",,,,
,PMC,Expression of Cellular Oncogene Bcl-xL Prevents Coronavirus-Induced Cell Death and Converts Acute Infection to Persistent Infection in Progenitor Rat Oligodendrocytes,http://dx.doi.org/10.1128/JVI.79.1.47-56.2005,PMC538726,,,"Murine coronavirus mouse hepatitis virus (MHV) causes persistent infection of the central nervous system (CNS) in rodents, which has been associated with demyelination. However, the precise mechanism of MHV persistence in the CNS remains elusive. Here we show that the progenitor oligodendrocytes (central glial 4 [CG-4] cells) derived from newborn rat brain were permissive to MHV infection, which resulted in cell death, although viral replication was restricted. Interestingly, treatment with fetal bovine serum or exogenous expression of cellular oncogene Bcl-xL prevented CG-4 cells from MHV-induced cell death. Significantly, overexpression of Bcl-xL alone was sufficient to convert acute to persistent, nonproductive infection in CG-4 cells. This finding indicates that intracellular factors rather than viral components play a critical role in establishing viral persistence in CNS cells. Although viral genomic RNAs continuously persisted in Bcl-xL-expressing CG-4 cells over 10 passages, infectious virus could no longer be isolated beyond 2 passages of the cell. Such a phenomenon resembles the persistent MHV infection in animal CNS. Thus, the establishment of a persistent, nonproductive infection in CG-4 cells may provide a useful in vitro model for studying viral persistence in animal CNS. The data also suggest that direct virus-host cell interaction is one of the underlying mechanisms that regulate viral persistence in CNS cells.",,"['Liu, Yin', 'Zhang, Xuming']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Infection of Golden Syrian Hamsters,http://dx.doi.org/10.1128/JVI.79.1.503-511.2005,PMC538722,,,"Small animal models are needed in order to evaluate the efficacy of candidate vaccines and antivirals directed against the severe acute respiratory syndrome coronavirus (SARS CoV). We investigated the ability of SARS CoV to infect 5-week-old Golden Syrian hamsters. When administered intranasally, SARS CoV replicates to high titers in the lungs and nasal turbinates. Peak replication in the lower respiratory tract was noted on day 2 postinfection (p.i.) and was cleared by day 7 p.i. Low levels of virus were present in the nasal turbinates of a few hamsters at 14 days p.i. Viral replication in epithelial cells of the respiratory tract was accompanied by cellular necrosis early in infection, followed by an inflammatory response coincident with viral clearance, focal consolidation in pulmonary tissue, and eventual pulmonary tissue repair. Despite high levels of virus replication and associated pathology in the respiratory tract, the hamsters showed no evidence of disease. Neutralizing antibodies were detected in sera at day 7 p.i., and mean titers at day 28 p.i. exceeded 1:400. Hamsters challenged with SARS CoV at day 28 p.i. were completely protected from virus replication and accompanying pathology in the respiratory tract. Comparing these data to the mouse model, SARS CoV replicates to a higher titer and for a longer duration in the respiratory tract of hamsters and is accompanied by significant pathology that is absent in mice. Viremia and extrapulmonary spread of SARS CoV to liver and spleen, which are seen in hamsters, were not detected in mice. The hamster, therefore, is superior to the mouse as a model for the evaluation of antiviral agents and candidate vaccines against SARS CoV replication.",,"['Roberts, Anjeanette', 'Vogel, Leatrice', 'Guarner, Jeannette', 'Hayes, Norman', 'Murphy, Brian', 'Zaki, Sherif', 'Subbarao, Kanta']",,,,
,PMC,Short Internal Sequences Involved in Replication and Virion Accumulation in a Subviral RNA of Turnip Crinkle Virus,http://dx.doi.org/10.1128/JVI.79.1.512-524.2005,PMC538713,,,"cis-acting sequences and structural elements in untranslated regions of viral genomes allow viral RNA-dependent RNA polymerases to correctly initiate and transcribe asymmetric levels of plus and minus strands during replication of plus-sense RNA viruses. Such elements include promoters, enhancers, and transcriptional repressors that may require interactions with distal RNA sequences for function. We previously determined that a non-sequence-specific hairpin (M1H) in the interior of a subviral RNA (satC) associated with Turnip crinkle virus is required for fitness and that its function might be to bridge flanking sequences (X. Sun and A. E. Simon, J. Virol. 77:7880-7889, 2003). To establish the importance of the flanking sequences in replication and satC-specific virion repression, segments on both sides of M1H were randomized and subjected to in vivo functional selection (in vivo SELEX). Analyses of winning (functional) sequences revealed three different conserved elements within the segments that could be specifically assigned roles in replication, virion repression, or both. One of these elements was also implicated in the molecular switch that releases the 3′ end from its interaction with the repressor hairpin H5, which is possibly involved in controlling the level of minus-strand synthesis.",,"['Sun, Xiaoping', 'Zhang, Guohua', 'Simon, Anne E.']",,,,
,PMC,Prevention of Virus Persistence and Protection against Immunopathology after Borna Disease Virus Infection of the Brain by a Novel Orf Virus Recombinant,http://dx.doi.org/10.1128/JVI.79.1.314-325.2005,PMC538698,,,"The Parapoxvirus Orf virus represents a promising candidate for novel vector vaccines due to its immune modulating properties even in nonpermissive hosts such as mouse or rat. The highly attenuated Orf virus strain D1701 was used to generate a recombinant virus (D1701-VrVp40) expressing nucleoprotein p40 of Borna disease virus, which represents a major antigen for the induction of a Borna disease virus-specific humoral and cellular immune response. Infection with Borna disease virus leads to distinct neurological symptoms mediated by the invasion of activated specific CD8(+) T cells into the infected brain. Usually, Borna disease virus is not cleared from the brain but rather persists in neural cells. In the present study we show for the first time that intramuscular application of the D1701-VrVp40 recombinant protected rats against Borna disease, and importantly, virus clearance from the infected brain was demonstrated in immunized animals. Even 4 and 8 months after the last immunization, all immunized animals were still protected against the disease. Initial characterization of the immune cells attracted to the infected brain areas suggested that D1701-VrVp40 mediated induction of B cells and antibody-producing plasma cells as well as T cells. These findings suggest the induction of various defense mechanisms against Borna disease virus. First studies on the role of antiviral cytokines indicated that D1701-VrVp40 immunization did not lead to an enhanced early response of gamma or alpha interferon or tumor necrosis factor alpha. Collectively, this study describes the potential of the Orf virus vector system in mediating long-lasting, protective antiviral immunity and eliminating this persistent virus infection without provoking massive neuronal damage.",,"['Henkel, Marco', 'Planz, Oliver', 'Fischer, Timo', 'Stitz, Lothar', 'Rziha, Hanns-Joachim']",,,,
,PMC,The Ubiquitin-Proteasome System Facilitates the Transfer of Murine Coronavirus from Endosome to Cytoplasm during Virus Entry,http://dx.doi.org/10.1128/JVI.79.1.644-648.2005,PMC538694,,,"The ubiquitin-proteasome system is involved in cellular endocytosis and maturation of some viruses. In this study, we found that proteasome inhibitors blocked mouse hepatitis virus replication at an early step in the viral life cycle. In the presence of MG132, the entering viruses accumulated in both the endosome and denser lysosome, suggesting that the ubiquitin-proteasome system is involved in the release of virus from the endosome to the cytosol during the virus entry step.",,"['Yu, Guann-Yi', 'Lai, Michael M. C.']",,,,
,PMC,Mass Spectroscopic Characterization of the Coronavirus Infectious Bronchitis Virus Nucleoprotein and Elucidation of the Role of Phosphorylation in RNA Binding by Using Surface Plasmon Resonance,http://dx.doi.org/10.1128/JVI.79.2.1164-1179.2005,PMC538594,,,"Phosphorylation of the coronavirus nucleoprotein (N protein) has been predicted to play a role in RNA binding. To investigate this hypothesis, we examined the kinetics of RNA binding between nonphosphorylated and phosphorylated infectious bronchitis virus N protein with nonviral and viral RNA by surface plasmon resonance (Biacore). Mass spectroscopic analysis of N protein identified phosphorylation sites that were proximal to RNA binding domains. Kinetic analysis, by surface plasmon resonance, indicated that nonphosphorylated N protein bound with the same affinity to viral RNA as phosphorylated N protein. However, phosphorylated N protein bound to viral RNA with a higher binding affinity than nonviral RNA, suggesting that phosphorylation of N protein determined the recognition of virus RNA. The data also indicated that a known N protein binding site (involved in transcriptional regulation) consisting of a conserved core sequence present near the 5′ end of the genome (in the leader sequence) functioned by promoting high association rates of N protein binding. Further analysis of the leader sequence indicated that the core element was not the only binding site for N protein and that other regions functioned to promote high-affinity binding.",,"['Chen, Hongying', 'Gill, Andrew', 'Dove, Brian K.', 'Emmett, Stevan R.', 'Kemp, C. Fred', 'Ritchie, Mark A.', 'Dee, Michael', 'Hiscox, Julian A.']",,,,
,PMC,"Characterization and Complete Genome Sequence of a Novel Coronavirus, Coronavirus HKU1, from Patients with Pneumonia",http://dx.doi.org/10.1128/JVI.79.2.884-895.2005,PMC538593,,,"Despite extensive laboratory investigations in patients with respiratory tract infections, no microbiological cause can be identified in a significant proportion of patients. In the past 3 years, several novel respiratory viruses, including human metapneumovirus, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and human coronavirus NL63, were discovered. Here we report the discovery of another novel coronavirus, coronavirus HKU1 (CoV-HKU1), from a 71-year-old man with pneumonia who had just returned from Shenzhen, China. Quantitative reverse transcription-PCR showed that the amount of CoV-HKU1 RNA was 8.5 to 9.6 × 10(6) copies per ml in his nasopharyngeal aspirates (NPAs) during the first week of the illness and dropped progressively to undetectable levels in subsequent weeks. He developed increasing serum levels of specific antibodies against the recombinant nucleocapsid protein of CoV-HKU1, with immunoglobulin M (IgM) titers of 1:20, 1:40, and 1:80 and IgG titers of <1:1,000, 1:2,000, and 1:8,000 in the first, second and fourth weeks of the illness, respectively. Isolation of the virus by using various cell lines, mixed neuron-glia culture, and intracerebral inoculation of suckling mice was unsuccessful. The complete genome sequence of CoV-HKU1 is a 29,926-nucleotide, polyadenylated RNA, with G+C content of 32%, the lowest among all known coronaviruses with available genome sequence. Phylogenetic analysis reveals that CoV-HKU1 is a new group 2 coronavirus. Screening of 400 NPAs, negative for SARS-CoV, from patients with respiratory illness during the SARS period identified the presence of CoV-HKU1 RNA in an additional specimen, with a viral load of 1.13 × 10(6) copies per ml, from a 35-year-old woman with pneumonia. Our data support the existence of a novel group 2 coronavirus associated with pneumonia in humans.",,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Chu, Chung-ming', 'Chan, Kwok-hung', 'Tsoi, Hoi-wah', 'Huang, Yi', 'Wong, Beatrice H. L.', 'Poon, Rosana W. S.', 'Cai, James J.', 'Luk, Wei-kwang', 'Poon, Leo L. M.', 'Wong, Samson S. Y.', 'Guan, Yi', 'Peiris, J. S. Malik', 'Yuen, Kwok-yung']",,,,
,PMC,A Complex Zinc Finger Controls the Enzymatic Activities of Nidovirus Helicases,http://dx.doi.org/10.1128/JVI.79.2.696-704.2005,PMC538568,,,"Nidoviruses (Coronaviridae, Arteriviridae, and Roniviridae) encode a nonstructural protein, called nsp10 in arteriviruses and nsp13 in coronaviruses, that is comprised of a C-terminal superfamily 1 helicase domain and an N-terminal, putative zinc-binding domain (ZBD). Previously, mutations in the equine arteritis virus (EAV) nsp10 ZBD were shown to block arterivirus reproduction by disrupting RNA synthesis and possibly virion biogenesis. Here, we characterized the ATPase and helicase activities of bacterially expressed mutant forms of nsp10 and its human coronavirus 229E ortholog, nsp13, and correlated these in vitro activities with specific virus phenotypes. Replacement of conserved Cys or His residues with Ala proved to be more deleterious than Cys-for-His or His-for-Cys replacements. Furthermore, denaturation-renaturation experiments revealed that, during protein refolding, Zn(2+) is essential for the rescue of the enzymatic activities of nidovirus helicases. Taken together, the data strongly support the zinc-binding function of the N-terminal domain of nidovirus helicases. nsp10 ATPase/helicase deficiency resulting from single-residue substitutions in the ZBD or deletion of the entire domain could not be complemented in trans by wild-type ZBD, suggesting a critical function of the ZBD in cis. Consistently, no viral RNA synthesis was detected after transfection of EAV full-length RNAs encoding ATPase/helicase-deficient nsp10 into susceptible cells. In contrast, diverse phenotypes were observed for mutants with enzymatically active nsp10, which in a number of cases correlated with the activities measured in vitro. Collectively, our data suggest that the ZBD is critically involved in nidovirus replication and transcription by modulating the enzymatic activities of the helicase domain and other, yet unknown, mechanisms.",,"['Seybert, Anja', 'Posthuma, Clara C.', 'van Dinten, Leonie C.', 'Snijder, Eric J.', 'Gorbalenya, Alexander E.', 'Ziebuhr, John']",,,,
,PMC,Natural History of a Recurrent Feline Coronavirus Infection and the Role of Cellular Immunity in Survival and Disease,http://dx.doi.org/10.1128/JVI.79.2.1036-1044.2005,PMC538555,,,"We describe the natural history, viral dynamics, and immunobiology of feline infectious peritonitis (FIP), a highly lethal coronavirus infection. A severe recurrent infection developed, typified by viral persistence and acute lymphopenia, with waves of enhanced viral replication coinciding with fever, weight loss, and depletion of CD4(+) and CD8(+) T cells. Our combined observations suggest a model for FIP pathogenesis in which virus-induced T-cell depletion and the antiviral T-cell response are opposing forces and in which the efficacy of early T-cell responses critically determines the outcome of the infection. Rising amounts of viral RNA in the blood, consistently seen in animals with end-stage FIP, indicate that progression to fatal disease is the direct consequence of a loss of immune control, resulting in unchecked viral replication. The pathogenic phenomena described here likely bear relevance to other severe coronavirus infections, in particular severe acute respiratory syndrome, for which multiphasic disease progression and acute T-cell lymphopenia have also been reported. Experimental FIP presents a relevant, safe, and well-defined model to study coronavirus-mediated immunosuppression and should provide an attractive and convenient system for in vivo testing of anticoronaviral drugs.",,"['de Groot-Mijnes, Jolanda D. F.', 'van Dun, Jessica M.', 'van der Most, Robbert G.', 'de Groot, Raoul J.']",,,,
,PMC,Quantitation of Adenovirus Genome During Acute Infection in Normal Children,,PMC2891530,,,"BACKGROUND: Adenovirus infection causes a wide range of clinical illness in normal children. New molecular techniques allow quantitation of viral genome to study the natural history of adenovirus infection and viral load in normal children. METHODS: Clinical samples were collected from 38 previously healthy, febrile children, and viral cultures were performed. Quantitative polymerase chain reaction (PCR) was used to detect adenovirus genome and to determine viral load. Adenovirus isolates were genotyped with a PCR-based assay. RESULTS: Adenovirus culture was positive in 6 children who were diagnosed with acute adenovirus infection. Throat swabs contained high copy numbers of adenovirus genome (1.6 × 10(6)–6 × 10(7) copies/swab) from 4 of 4 adenovirus culture-positive children. Only 2 of 32 adenovirus culture-negative children had detectable adenovirus genome from throat swabs, but with a lower copy number (8 × 10(2) copies/swab). Adenovirus genome was not detected in blood samples from 5 of 6 adenovirus culture-positive children with uncomplicated upper respiratory tract infection and from all adenovirus culture-negative children. High level viremia (1.8 × 10(8)/ml) was detected in an adenovirus culture-positive 6-month-old infant with fever, pneumonia, conjunctivitis and hepatitis. Subsequent reduction in viral load paralleled her clinical recovery. Adenovirus viruria (1 × 10(9) copies/ml) with normal urinanalysis was detected in another adenovirus culture-positive child. All 6 adenovirus isolates were genotyped as adenovirus type 7h. CONCLUSION: Viral load assessment in clinical samples determined by quantitative PCR can be useful in the diagnosis of adenovirus infection in immunocompetent, febrile children.",,"['Shike, Hiroko', 'Shimizu, Chisato', 'Kanegaye, John', 'Foley, Jennifer L.', 'Burns, Jane C.']",,,,
,PMC,Development of an Interactive Bioterrorism and Emerging Infections Curriculum for Medical Students and Internal Medicine Residents,,PMC2569989,,,"While awareness of bioterrorism threats and emerging infectious diseases has resulted in an increased sense of urgency to improve the knowledge base and response capability of physicians, few medical schools and residency programs have curricula in place to teach these concepts. Public health agencies are an essential component of a response to these types of emergencies. Public health education during medical school is usually limited to the non-clinical years. With collaboration from our local public health agency, the Emory University School of Medicine developed a curriculum in bioterrorism and emerging infections. By implementing this curriculum in the clinical years of medical school and residency programs, we seek to foster improved interactions between clinicians and their local public health agencies.",,"['Cassoobhoy, Murtaza', 'Wetterhall, Scott F.', 'Collins, Darren F.', 'Cantey, Paul T.', 'Iverson, Christopher J.', 'Rudnick, Judith R.', 'Del Rio, Carlos']",,,,
,PMC,Team Epi-Aid: Graduate Student Assistance with Urgent Public Health Response,,PMC2569985,,,"Team Epi-Aid provides graduate students with practical public health experience through participation in outbreak investigations and other applied projects with state and local health departments in North Carolina. It is an initiative of the North Carolina Center for Public Health Preparedness in the North Carolina Institute for Public Health at the University of North Carolina School of Public Health. The program allows state and local health departments access to volunteers and technical expertise from the university when they need assistance. It requires close collaboration with state and county health departments. Team Epi-Aid provides the opportunity for integrated learning with students and faculty within the departments of the School of Public Health, and through recent expansion, within the schools of Medicine and Pharmacy. Orientations are conducted each semester and formal training is provided as needed. Team Epi-Aid has been popular, with 58 active student participants contributing 1,465 hours of service during the initiative's first 21 months.",,"MacDonald, Pia D.M.",,,,
,PMC,Public Health Strategy and the Police Powers of the State,,PMC2569983,,,,,"['Galva, Jorge E.', 'Atchison, Christopher', 'Levey, Samuel']",,,,
,PMC,Identification of Structural Domains Involved in Astrovirus Capsid Biology,http://dx.doi.org/10.1089/vim.2005.18.17,PMC1393289,,,"Coat proteins of non-enveloped, icosahedral viruses must perform a variety of functions during their life cycle such as assembly of the coat protein subunits into a closed shell, specific encapsidation of the viral nucleic acid, maturation of the capsid, interaction with host receptors and disassembly to deliver the genetic information into the newly-infected cell. A thorough understanding of the multiple capsid properties at the molecular level is required in order to identify potential targets for antiviral therapy and the prevention of viral disease. The system we have chosen for study are the astroviruses, a family of icosahedral, single-stranded RNA viruses that cause disease in mammals and birds. Very little is known about what regions of the coat protein contribute to the diverse capsid functions. This review will present novel structural predictions for the coat protein sequence of different astrovirus family members. Based on these predictions, we hypothesize that the assembly and RNA packaging functions of the astrovirus coat protein constitutes an individual domain distinct from the determinants required for receptor binding and internalization. Information derived from these structural predictions will serve as an important tool in designing experiments to understand astrovirus biology.",,"Krishna, Neel K.",,,,
,PMC,High rate of viral evolution associated with the emergence of carnivore parvovirus,http://dx.doi.org/10.1073/pnas.0406765102,PMC544290,,,"Canine parvovirus (CPV) is an emerging DNA virus that was first observed to cause disease in canines in 1978 and has since become a ubiquitous pathogen worldwide. CPV emerged from feline panleukopenia parvovirus (FPLV) or a closely related virus, differing at several key amino acid residues. Here we characterize the evolutionary processes underlying the emergence of CPV. Although FPLV has remained an endemic infection in its host populations, we show that, since the 1970s, the newly emerged CPV has undergone an epidemic-like pattern of logistic/exponential growth, effectively doubling its population size every few years. This rapid population growth was associated with a lineage of CPV that acquired a broader host range and greater infectivity. Recombination played no role in the emergence of CPV. Rather, any preexisting variation in the donor species and the subsequent rapid adaptation of the virus to canines were likely dependent on a high rate of mutation and the positive selection of mutations in the major capsid gene. Strikingly, although these single-stranded viruses have a DNA genome and use cellular replication machinery, their rate of nucleotide substitution is closer to that of RNA viruses than to that of double-stranded DNA viruses.",,"['Shackelton, Laura A.', 'Parrish, Colin R.', 'Truyen, Uwe', 'Holmes, Edward C.']",,,,
,PMC,Effect of restricted freedom on health in China,,PMC535962,,,"China has shown how a non-democratic system can benefit the health of the population, but can health gains be sustained as the country becomes freer?",,"['Hesketh, Therese', 'Zhu, Wei Xing']",,,,
,PMC,The structure of the TrmE GTP-binding protein and its implications for tRNA modification,http://dx.doi.org/10.1038/sj.emboj.7600507,PMC544919,,,"TrmE is a 50 kDa guanine nucleotide-binding protein conserved between bacteria and man. It is involved in the modification of uridine bases (U34) at the first anticodon (wobble) position of tRNAs decoding two-family box triplets. The precise role of TrmE in the modification reaction is hitherto unknown. Here, we report the X-ray structure of TrmE from Thermotoga maritima. The structure reveals a three-domain protein comprising the N-terminal α/β domain, the central helical domain and the G domain, responsible for GTP binding and hydrolysis. The N-terminal domain induces dimerization and is homologous to the tetrahydrofolate-binding domain of N,N-dimethylglycine oxidase. Biochemical and structural studies show that TrmE indeed binds formyl-tetrahydrofolate. A cysteine residue, necessary for modification of U34, is located close to the C1-group donor 5-formyl-tetrahydrofolate, suggesting a direct role of TrmE in the modification analogous to DNA modification enzymes. We propose a reaction mechanism whereby TrmE actively participates in the formylation reaction of uridine and regulates the ensuing hydrogenation reaction of a Schiff's base intermediate.",,"['Scrima, Andrea', 'Vetter, Ingrid R', 'Armengod, M Eugenia', 'Wittinghofer, Alfred']",,,,
,PMC,Structure of a proteolytically resistant core from the severe acute respiratory syndrome coronavirus S2 fusion protein,http://dx.doi.org/10.1073/pnas.0406128102,PMC539766,,,"A coronavirus (CoV) has recently been identified as the causative agent of the severe acute respiratory syndrome (SARS) in humans. CoVs enter target cells through fusion of viral and cellular membranes mediated by the viral envelope glycoprotein S. We have determined by x-ray crystallography the structure of a proteolytically stable core fragment from the heptad repeat (HR) regions HR1 and HR2 of the SARS-CoV S protein. We have also determined the structure of an HR1-HR2 S core fragment, containing a shorter HR1 peptide and a C-terminally longer HR2 peptide that extends up to the transmembrane region. In these structures, three HR1 helices form a parallel coiled-coil trimer, whereas three HR2 peptides pack in an oblique and antiparallel fashion into the coiled-coil hydrophobic grooves, adopting mixed extended and α-helical conformations as in postfusion paramyxoviruses F proteins structures. Our structure positions a previously proposed internal fusion peptide adjacent to the N-terminus of HR1. Peptides from the HR2 region of SARS-CoV S have been shown to inhibit viral entry and infection in vitro. The structures presented here can thus open the path to the design of small-molecule inhibitors of viral entry and candidate vaccine antigens against this virus.",,"['Supekar, Vinit M.', 'Bruckmann, Chiara', 'Ingallinella, Paolo', 'Bianchi, Elisabetta', 'Pessi, Antonello', 'Carfí, Andrea']",,,,
,PMC,Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap,http://dx.doi.org/10.1073/pnas.0406927102,PMC539790,,,"The eukaryotic translation initiation factor eIF4E is deregulated in many human cancers, and its overexpression in cells leads to malignant transformation. Oncogenic properties of eIF4E are directly linked to its ability to bind 7-methyl guanosine of the 5′ mRNA. Here, we observe that the antiviral guanosine analogue ribavirin binds to eIF4E with micromolar affinity at the functional site used by 7-methyl guanosine mRNA cap, competes with eIF4E:mRNA binding, and, at low micromolar concentrations, selectively disrupts eIF4E subcellular organization and transport and translation of mRNAs posttranscriptionally regulated by eIF4E, thereby reducing levels of oncogenes such as cyclin D1. Ribavirin potently suppresses eIF4E-mediated oncogenic transformation of murine cells in vitro, of tumor growth of a mouse model of eIF4E-dependent human squamous cell carcinoma in vivo, and of colony formation of eIF4E-dependent acute myelogenous leukemia cells derived from human patients. These findings describe a specific, potent, and unforeseen mechanism of action of ribavirin. Quantum mechanical and NMR structural studies offer directions for the development of derivatives with improved cytostatic and antiviral properties. In all, ribavirin's association with eIF4E may provide a pharmacologic means for the interruption of posttranscriptional networks of oncogenes that maintain and enhance neoplasia and malignancy in human cancer.",,"['Kentsis, Alex', 'Topisirovic, Ivan', 'Culjkovic, Biljana', 'Shao, Ling', 'Borden, Katherine L. B.']",,,,
,PMC,High-yield expression of recombinant SARS coronavirus nucleocapsid protein in methylotrophic yeast Pichia pastoris,http://dx.doi.org/10.3748/wjg.v10.i24.3602,PMC4612000,,,"AIM: Nucleocapsid (N) protein plays an important role in reproduction and pathological reaction of severe acute respiratory syndrome (SARS) coronavirus (SCoV), the antigenicity of the protein is better than spike (S) protein. This study was to find a highly specific and antigenic recombinant SCoV nucleocapsid (rSCoVN) protein, and to provide a basis for further researches on early diagnosis of SARS. METHODS: Full length cDNA of SCoV nucleocapsid (SCoVN) protein was amplified through polymerase chain reaction (PCR) and cloned into yeast expression vector pPIC3.5K to construct plasmid of pPIC3.5K-SCoVN. The plasmid was linearized and then transformed into Pichia pastoris (P.pastoris) GS115 (His(-)Mut(+)) by electroporation. His(+)Mut(+) recombinant strains were identified by PCR and cultivated on MM/MD plates. The influence of different factors on biomass and rSCoVN protein production during induction phase, such as various induction media, dissolved oxygen (DO) and different final concentrations of methanol, was subsequently studied. The expression level and activation were detected by SDS-PAGE and Western-blot respectively. RESULTS: All of the recombinants were His(+)Mut(+) after transformation of P.pastoris with linearized plasmids. The BMMY medium was optimal for recombinant ScoVN (rSCoVN) protein expression and growth of the recombinant strains. The final optimal concentration of methanol was 20 mL/L, the DO had a significant effect on rSCoVN protein expression and growth of recombinant strains. The rSCoVN protein expressed in recombinant strains was about 8% of the total cell protein, 520 mg/L of rSCoVN protein was achieved, and a maximum cell A at 600 nm of 62 was achieved in shake flask culture. The rSCoVN protein had a high specificity against mouse-anti-SARS-CoVN-mAb and SARS positive sera, but had no cross-reaction with normal human serum. The biological activity of rSCoVN expressed in P.pastoris was about 4-fold higher than that expressed in E.coli when the same rSCoVN protein quantity was used. CONCLUSION: Active recombinant severe acute respiratory syndrome (SARS) coronavirus nucleocapsid (rSCoVN) protein can be successfully expressed in recombinant methylotrophic yeast P.pastoris GS115. The rSCoVN protein has a high specificity against SARS-CoVN-mAb and SARS positive sera, but has no cross-reaction with normal human serum. This provides a basis for further researches on the early diagnosis of SARS and the mechanism of SCoV.",,"['Liu, Ru-Shi', 'Yang, Kun-Yu', 'Lin, Jian', 'Lin, Yi-Wei', 'Zhang, Zhi-Hong', 'Zhang, Jun', 'Xia, Ning-Shao']",,,,
,PMC,Inhaling to mitigate exhaled bioaerosols,http://dx.doi.org/10.1073/pnas.0408159101,PMC536048,,,"Humans commonly exhale aerosols comprised of small droplets of airway-lining fluid during normal breathing. These “exhaled bioaerosols” may carry airborne pathogens and thereby magnify the spread of certain infectious diseases, such as influenza, tuberculosis, and severe acute respiratory syndrome. We hypothesize that, by altering lung airway surface properties through an inhaled nontoxic aerosol, we might substantially diminish the number of exhaled bioaerosol droplets and thereby provide a simple means to potentially mitigate the spread of airborne infectious disease independently of the identity of the airborne pathogen or the nature of any specific therapy. We find that some normal human subjects expire many more bioaerosol particles than other individuals during quiet breathing and therefore bear the burden of production of exhaled bioaerosols. Administering nebulized isotonic saline to these “high-producer” individuals diminishes the number of exhaled bioaerosol particles expired by 72.10 ± 8.19% for up to 6 h. In vitro and in vivo experiments with saline and surfactants suggest that the mechanism of action of the nebulized saline relates to modification of the physical properties of the airway-lining fluid, notably surface tension.",,"['Edwards, David A.', 'Man, Jonathan C.', 'Brand, Peter', 'Katstra, Jeffrey P.', 'Sommerer, K.', 'Stone, Howard A.', 'Nardell, Edward', 'Scheuch, Gerhard']",,,,
,PMC,Novel Nonnucleoside Inhibitor of Hepatitis C Virus RNA-Dependent RNA Polymerase,http://dx.doi.org/10.1128/AAC.48.12.4813-4821.2004,PMC529219,,,"A novel nonnucleoside inhibitor of hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp), [(1R)-5-cyano-8-methyl-1-propyl-1,3,4,9-tetrahydropyano[3,4-b]indol-1-yl] acetic acid (HCV-371), was discovered through high-throughput screening followed by chemical optimization. HCV-371 displayed broad inhibitory activities against the NS5B RdRp enzyme, with 50% inhibitory concentrations ranging from 0.3 to 1.8 μM for 90% of the isolates derived from HCV genotypes 1a, 1b, and 3a. HCV-371 showed no inhibitory activity against a panel of human polymerases, including mitochondrial DNA polymerase gamma, and other unrelated viral polymerases, demonstrating its specificity for the HCV polymerase. A single administration of HCV-371 to cells containing the HCV subgenomic replicon for 3 days resulted in a dose-dependent reduction of the steady-state levels of viral RNA and protein. Multiple treatments with HCV-371 for 16 days led to a >3-log(10) reduction in the HCV RNA level. In comparison, multiple treatments with a similar inhibitory dose of alpha interferon resulted in a 2-log(10) reduction of the viral RNA level. In addition, treatment of cells with a combination of HCV-371 and pegylated alpha interferon resulted in an additive antiviral activity. Within the effective antiviral concentrations of HCV-371, there was no effect on cell viability and metabolism. The intracellular antiviral specificity of HCV-371 was demonstrated by its lack of activity in cells infected with several DNA or RNA viruses. Fluorescence binding studies show that HCV-371 binds the NS5B with an apparent dissociation constant of 150 nM, leading to high selectivity and lack of cytotoxicity in the antiviral assays.",,"['Howe, Anita Y. M.', 'Bloom, Johnathan', 'Baldick, Carl J.', 'Benetatos, Christopher A.', 'Cheng, Huiming', 'Christensen, Joel S.', 'Chunduru, Srinivas K.', 'Coburn, Glen A.', 'Feld, Boris', 'Gopalsamy, Ariamala', 'Gorczyca, William P.', 'Herrmann, Steve', 'Johann, Stephen', 'Jiang, Xiaoqun', 'Kimberland, Michelle L.', 'Krisnamurthy, Girija', 'Olson, Matthew', 'Orlowski, Mark', 'Swanberg, Steve', 'Thompson, Ian', 'Thorn, Megan', 'Del Vecchio, Alfred', 'Young, Dorothy C.', 'van Zeijl, Marja', 'Ellingboe, John W.', 'Upeslacis, Janis', 'Collett, Marc', 'Mansour, Tarek S.', ""O'Connell, John F.""]",,,,
,PMC,False-Positive Results in a Recombinant Severe Acute Respiratory Syndrome-Associated Coronavirus (SARS-CoV) Nucleocapsid Enzyme-Linked Immunosorbent Assay Due to HCoV-OC43 and HCoV-229E Rectified by Western Blotting with Recombinant SARS-CoV Spike Polypeptide,http://dx.doi.org/10.1128/JCM.42.12.5885-5888.2004,PMC535232,,,"Using paired serum samples obtained from patients with illness associated with increases in anti-human coronavirus OC43 (HCoV-OC43) or anti-HCoV-229E antibodies, we examined the possibility of false-positive results detected in a recombinant severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein immunoglobulin G enzyme-linked immunosorbent assay (ELISA). Three of the 21 and 1 of the 7 convalescent-phase serum samples from persons with increases in antibodies against HCoV-OC43 and HCoV-229E, respectively, tested positive by the recombinant SARS-CoV nucleocapsid protein-based ELISA. None of these samples were found to contain a specific antibody in the recombinant SARS-CoV spike polypeptide-based Western blot assay.",,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Wong, Beatrice H. L.', 'Chan, Kwok-Hung', 'Hui, Wai-Ting', 'Kwan, Grace S. W.', 'Peiris, J. S. Malik', 'Couch, Robert B.', 'Yuen, Kwok-Yung']",,,,
,PMC,Sequencing Needs for Viral Diagnostics,http://dx.doi.org/10.1128/JCM.42.12.5472-5476.2004,PMC535215,,,"We built a system to guide decisions regarding the amount of genomic sequencing required to develop diagnostic DNA signatures, which are short sequences that are sufficient to uniquely identify a viral species. We used our existing DNA diagnostic signature prediction pipeline, which selects regions of a target species genome that are conserved among strains of the target (for reliability, to prevent false negatives) and unique relative to other species (for specificity, to avoid false positives). We performed simulations, based on existing sequence data, to assess the number of genome sequences of a target species and of close phylogenetic relatives (near neighbors) that are required to predict diagnostic signature regions that are conserved among strains of the target species and unique relative to other bacterial and viral species. For DNA viruses such as variola (smallpox), three target genomes provide sufficient guidance for selecting species-wide signatures. Three near-neighbor genomes are critical for species specificity. In contrast, most RNA viruses require four target genomes and no near-neighbor genomes, since lack of conservation among strains is more limiting than uniqueness. Severe acute respiratory syndrome and Ebola Zaire are exceptional, as additional target genomes currently do not improve predictions, but near-neighbor sequences are urgently needed. Our results also indicate that double-stranded DNA viruses are more conserved among strains than are RNA viruses, since in most cases there was at least one conserved signature candidate for the DNA viruses and zero conserved signature candidates for the RNA viruses.",,"['Gardner, Shea N.', 'Lam, Marisa W.', 'Mulakken, Nisha J.', 'Torres, Clinton L.', 'Smith, Jason R.', 'Slezak, Tom R.']",,,,
,PMC,SARS related preventive and risk behaviours practised by Hong Kong-mainland China cross border travellers during the outbreak of the SARS epidemic in Hong Kong,http://dx.doi.org/10.1136/jech.2003.017483,PMC1732647,,,"Objectives: To investigate patterns of behaviours and attitudes related to SARS prevention in the Hong Kong cross border traveller population. Settings: A survey was carried out at the Hong Kong-China cross border checkpoint in the middle of the epidemic. Participants: A total of 839 Hong Kong adult residents returning to Hong Kong from mainland China were surveyed. Main outcome measures: Practice of preventive measures and relevant behaviours and attitudes. Results: Around 40% of the respondents were using masks all or most of the time in public places or washing their hands frequently (>10 times per day) and about one third avoided visiting crowded places in mainland China. Such figures were however lower than those practised by the general public in Hong Kong. SARS related perceptions, such as perceived risk of transmission and efficacy, etc, were associated with mask use and not visiting crowded places, but not with hand washing, which was associated with duration of stay. Gender differences were also observed. Around 70% of the travellers would have delayed medical consultation for influenza-like illness in China; 12.7% would not wear masks during such episodes of illness. Furthermore, about 30% of the respondents used to wear masks in Hong Kong but not in mainland China. Conclusions: The findings have implications on cross border prevention of SARS. It seems that those travelling during the SARS epidemic were a ""self selected"" group, and they were using less preventive measures. Special attention and intervention need to be provided to travellers to prevent a second wave cross border transmission of the disease.",,"['Lau, J.', 'Yang, X.', 'Tsui, H', 'Pang, E.']",,,,
,PMC,Lead free,,PMC1732642,,,,,"Tafari, L.",,,,
,PMC,"Overexpression of 7a, a Protein Specifically Encoded by the Severe Acute Respiratory Syndrome Coronavirus, Induces Apoptosis via a Caspase-Dependent Pathway",http://dx.doi.org/10.1128/JVI.78.24.14043-14047.2004,PMC533950,,,"Besides genes that are homologous to proteins found in other coronaviruses, the severe acute respiratory syndrome coronavirus genome also contains nine other potential open reading frames. Previously, we have characterized the expression and cellular localization of two of these “accessory” viral proteins, 3a (previously termed U274) and 7a (previously termed U122). In this study, we further examined whether they can induce apoptosis, which has been observed clinically. We showed that the overexpression of 7a, but not of 3a or the viral structural proteins, nucleocapsid, membrane, and envelope, induces apoptosis. 7a induces apoptosis via a caspase-dependent pathway and in cell lines derived from different organs, including lung, kidney, and liver.",,"['Tan, Yee-Joo', 'Fielding, Burtram C.', 'Goh, Phuay-Yee', 'Shen, Shuo', 'Tan, Timothy H. P.', 'Lim, Seng Gee', 'Hong, Wanjin']",,,,
,PMC,Nucleolar Localization of Human Hepatitis B Virus Capsid Protein,http://dx.doi.org/10.1128/JVI.78.24.13653-13668.2004,PMC533942,,,"Wild-type human hepatitis B virus (HBV) exhibits selective export of virions containing mature genomes. In contrast, changing an isoleucine to a leucine at amino acid 97 (I97L) of the HBV core antigen (HBcAg) causes it to release immature genomes. To elucidate the structure-function relationship of HBcAg at amino acid 97, we systematically replaced the isoleucine residue at this position with 18 other amino acids via mutagenesis. Twelve of the 18 mutants exhibited no significant phenotype, while five new mutants displayed strong phenotypes. The I97D mutant had a near lethal phenotype, the I97P mutant exhibited a significantly reduced level of virion secretion, and the I97G mutant lacked the full-length relaxed circular form of viral DNA. The tip of the spike of the capsid particle is known to contain a predominant B-cell epitope. However, the recognition of this exposed epitope by an anti-HBc antibody appeared to be affected by the I97E mutation or by histidine tagging at the C terminus of mutant HBcAg, which is presumably in the capsid interior. Surprisingly, the nuclear HBcAg of mutants I97E and I97W, produced from either a replicon or an expression vector, was found to be colocalized with nucleolin and B23 at a frequency of nearly 100% by confocal immunofluorescence microscopy. In contrast, this colocalization occurred with wild-type HBcAg only to a limited extent. We also noted that nucleolin-colocalizing cells were often binucleated or apoptotic, suggesting that the presence of HBcAg in the nucleolus may perturb cytokinesis. The mechanism of this phenomenon and its potential involvement in liver pathogenesis are discussed. To our knowledge, this is the first report of nucleolar HBcAg in culture.",,"['Ning, Bo', 'Shih, Chiaho']",,,,
,PMC,A Conserved Histidine in the ij Loop of the Semliki Forest Virus E1 Protein Plays an Important Role in Membrane Fusion,http://dx.doi.org/10.1128/JVI.78.24.13543-13552.2004,PMC533937,,,"The enveloped alphavirus Semliki Forest virus (SFV) infects cells via a low pH-triggered membrane fusion reaction mediated by the E1 protein. E1 is a class II fusion protein that contains the hydrophobic fusion peptide loop and converts to a stable homotrimer during the fusion reaction. Intriguingly, the fusion loop is closely associated with a loop connecting the i and j β-strands. This ij loop plays a role in the cholesterol dependence of membrane fusion and is specifically susceptible to proteolysis in the protease-resistant E1 homotrimer. The SFV ij loop contains a histidine residue at position 230. Sequence comparisons revealed that an analogous histidine is completely conserved in all alphavirus and flavivirus fusion proteins. An E1 H230A mutant was constructed using the SFV infectious clone. Although cells infected with H230A RNA produced virus particles, these virions were completely noninfectious and were blocked in both cell-cell fusion and lipid mixing assays. The H230A virions efficiently bound to cell surface receptors and responded to low pH by undergoing acid-dependent conformational changes including dissociation of the E1/E2 dimer, exposure of the fusion loop, association with target liposomes, exposure of acid-conformation-specific epitopes, and formation of the stable E1 homotrimer. Studies with a soluble fragment of E1 showed that the mutant protein was defective in lipid-dependent conformational changes. Our results indicate that the E1 ij loop and the conserved H230 residue play a critical role in alphavirus-membrane fusion and suggest the presence of a previously undescribed late intermediate in the fusion reaction.",,"['Chanel-Vos, Chantal', 'Kielian, Margaret']",,,,
,PMC,Identification of Severe Acute Respiratory Syndrome Coronavirus Replicase Products and Characterization of Papain-Like Protease Activity,http://dx.doi.org/10.1128/JVI.78.24.13600-13612.2004,PMC533933,,,"Gene 1 of the coronavirus associated with severe acute respiratory syndrome (SARS) encodes replicase polyproteins that are predicted to be processed into 16 nonstructural proteins (nsps 1 to 16) by two viral proteases, a papain-like protease (PLpro) and a 3C-like protease (3CLpro). Here, we identify SARS coronavirus amino-terminal replicase products nsp1, nsp2, and nsp3 and describe trans-cleavage assays that characterize the protease activity required to generate these products. We generated polyclonal antisera to glutathione S-transferase-replicase fusion proteins and used the antisera to detect replicase intermediates and products in pulse-chase experiments. We found that nsp1 (p20) is rapidly processed from the replicase polyprotein. In contrast, processing at the nsp2/3 site is less efficient, since a ≈300-kDa intermediate (NSP2-3) is detected, but ultimately nsp2 (p71) and nsp3 (p213) are generated. We found that SARS coronavirus replicase products can be detected by 4 h postinfection in the cytoplasm of infected cells and that nsps 1 to 3 colocalize with newly synthesized viral RNA in punctate, perinuclear sites consistent with their predicted role in viral RNA synthesis. To determine if PLpro is responsible for processing these products, we cloned and expressed the PLpro domain and the predicted substrates and established PLpro trans-cleavage assays. We found that the PLpro domain is sufficient for processing the predicted nsp1/2 and nsp2/3 sites. Interestingly, expression of an extended region of PLpro that includes the downstream hydrophobic domain was required for processing at the predicted nsp3/4 site. We found that the hydrophobic domain is inserted into membranes and that the lumenal domain is glycosylated at asparagine residues 2249 and 2252. Thus, the hydrophobic domain may anchor the replication complex to intracellular membranes. These studies revealed that PLpro can cleave in trans at the three predicted cleavage sites and that it requires membrane association to process the nsp3/4 cleavage site.",,"['Harcourt, Brian H.', 'Jukneliene, Dalia', 'Kanjanahaluethai, Amornrat', 'Bechill, John', 'Severson, Kari M.', 'Smith, Catherine M.', 'Rota, Paul A.', 'Baker, Susan C.']",,,,
,PMC,Genetic Screen for Monitoring Severe Acute Respiratory Syndrome Coronavirus 3C-Like Protease,http://dx.doi.org/10.1128/JVI.78.24.14057-14061.2004,PMC533918,,,"A novel coronavirus (SCoV) is the etiological agent of severe acute respiratory syndrome. Site-specific proteolysis plays a critical role in regulating a number of cellular and viral processes. Since the main protease of SCoV, also termed 3C-like protease, is an attractive target for drug therapy, we have developed a safe, simple, and rapid genetic screen assay to monitor the activity of the SCoV 3C-like protease. This genetic system is based on the bacteriophage lambda regulatory circuit, in which the viral repressor cI is specifically cleaved to initiate the lysogenic-to-lytic switch. A specific target for the SCoV 3C-like protease, P1/P2 (SAVLQ/SGFRK), was inserted into the lambda phage cI repressor. The target specificity of the SCoV P1/P2 repressor was evaluated by coexpression of this repressor with a chemically synthesized SCoV 3C-like protease gene construct. Upon infection of Escherichia coli cells containing the two plasmids encoding the cI. SCoV P1/P2-cro and the β-galactosidase-SCoV 3C-like protease constructs, lambda phage replicated up to 2,000-fold more efficiently than in cells that did not express the SCoV 3C-like protease. This simple and highly specific assay can be used to monitor the activity of the SCoV 3C-like protease, and it has the potential to be used for screening specific inhibitors.",,"['Parera, Mariona', 'Clotet, Bonaventura', 'Martinez, Miguel Angel']",,,,
,PMC,Recombinant Infectious Bronchitis Coronavirus Beaudette with the Spike Protein Gene of the Pathogenic M41 Strain Remains Attenuated but Induces Protective Immunity,http://dx.doi.org/10.1128/JVI.78.24.13804-13811.2004,PMC533908,,,"We have replaced the ectodomain of the spike (S) protein of the Beaudette strain (Beau-R; apathogenic for Gallus domesticus chickens) of avian infectious bronchitis coronavirus (IBV) with that from the pathogenic M41 strain to produce recombinant IBV BeauR-M41(S). We have previously shown that this changed the tropism of the virus in vitro (R. Casais, B. Dove, D. Cavanagh, and P. Britton, J. Virol. 77:9084-9089, 2003). Herein we have assessed the pathogenicity and immunogenicity of BeauR-M41(S). There were no consistent differences in pathogenicity between the recombinant BeauR-M41(S) and its apathogenic parent Beau-R (based on snicking, nasal discharge, wheezing, watery eyes, rales, and ciliostasis in trachea), and both replicated poorly in trachea and nose compared to M41; the S protein from the pathogenic M41 had not altered the apathogenic nature of Beau-R. Both Beau-R and BeauR-M41(S) induced protection against challenge with M41 as assessed by absence of recovery of challenge virus and nasal exudate. With regard to snicking and ciliostasis, BeauR-M41(S) induced greater protection (seven out of nine chicks [77%]; assessed by ciliostasis) than Beau-R (one out of nine; 11%) but less than M41 (100%). The greater protection induced by BeauR-M41(S) against M41 may be related to the ectodomain of the spike protein of Beau-R differing from that of M41 by 4.1%; a small number of epitopes on the S protein may play a disproportionate role in the induction of immunity. The results are promising for the prospects of S-gene exchange for IBV vaccine development.",,"['Hodgson, Teri', 'Casais, Rosa', 'Dove, Brian', 'Britton, Paul', 'Cavanagh, Dave']",,,,
,PMC,"SYNCRIP, a Member of the Heterogeneous Nuclear Ribonucleoprotein Family, Is Involved in Mouse Hepatitis Virus RNA Synthesis",http://dx.doi.org/10.1128/JVI.78.23.13153-13162.2004,PMC525026,,,"Several cellular proteins, including several heterogeneous nuclear ribonucleoproteins (hnRNPs), have been shown to function as regulatory factors for mouse hepatitis virus (MHV) RNA synthesis as a result of their binding to the 5′ and 3′ untranslated regions (UTRs) of the viral RNA. Here, we identified another cellular protein, p70, which has been shown by UV cross-linking to bind both the positive- and negative-strand UTRs of MHV RNA specifically. We purified p70 with a a one-step RNA affinity purification procedure with the biotin-labeled 5′-UTR. Matrix-assisted laser desorption ionization (MALDI)-mass spectrometry identified it as synaptotagmin-binding cytoplasmic RNA-interacting protein (SYNCRIP). SYNCRIP is a member of the hnRNP family and localizes largely in the cytoplasm. The p70 was cross-linked to the MHV positive- or negative-strand UTR in vitro and in vivo. The bacterially expressed SYNCRIP was also able to bind to the 5′-UTR of both strands. The SYNCRIP-binding site was mapped to the leader sequence of the 5′-UTR, requiring the UCUAA repeat sequence. To investigate the functional significance of SYNCRIP in MHV replication, we expressed a full-length or a C-terminally truncated form of SYNCRIP in mammalian cells expressing the MHV receptor. The overexpression of either form of SYNCRIP inhibited syncytium formation induced by MHV infection. Furthermore, downregulation of the endogenous SYNCRIP with a specific short interfering RNA delayed MHV RNA synthesis; in contrast, overexpression or downregulation of SYNCRIP did not affect MHV translation. These results suggest that SYNCRIP may be directly involved in MHV RNA replication as a positive regulator. This study identified an additional cellular hnRNP as an MHV RNA-binding protein potentially involved in viral RNA synthesis.",,"['Choi, Keum S.', 'Mizutani, Akihiro', 'Lai, Michael M. C.']",,,,
,PMC,"Mechanisms in photodynamic therapy: part one—-photosensitizers, photochemistry and cellular localization",http://dx.doi.org/10.1016/S1572-1000(05)00007-4,PMC4108220,,,"The use of non-toxic dyes or photosensitizers (PS) in combination with harmless visible light that is known as photodynamic therapy (PDT) has been known for over a hundred years, but is only now becoming widely used. Originally developed as a tumor therapy, some of its most successful applications are for non-malignant disease. In a series of three reviews we will discuss the mechanisms that operate in the field of PDT. Part one discusses the recent explosion in discovery and chemical synthesis of new PS. Some guidelines on how to choose an ideal PS for a particular application are presented. The photochemistry and photophysics of PS and the two pathways known as Type I (radicals and reactive oxygen species) and Type II (singlet oxygen) photochemical processes are discussed. To carry out PDT effectively in vivo, it is necessary to ensure sufficient light reaches all the diseased tissue. This involves understanding how light travels within various tissues and the relative effects of absorption and scattering. The fact that most of the PS are also fluorescent allows various optical imaging and monitoring strategies to be combined with PDT. The most important factor governing the outcome of PDT is how the PS interacts with cells in the target tissue or tumor, and the key aspect of this interaction is the subcellular localization of the PS. Examples of PS that localize in mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes are given. Finally the use of 5-aminolevulinic acid as a natural precursor of the heme biosynthetic pathway, stimulates accumulation of the PS protoporphyrin IX is described.",,"['Castano, Ana P.', 'Demidova, Tatiana N.', 'Hamblin, Michael R.']",,,,
,PMC,Readmission rates and life threatening events in COPD survivors treated with non-invasive ventilation for acute hypercapnic respiratory failure,http://dx.doi.org/10.1136/thx.2004.024307,PMC1746916,,,"Background: Non-invasive ventilation (NIV) has been shown to reduce intubation and in-hospital mortality in patients with chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure (AHRF). However, little information exists on the outcomes following discharge. A study was undertaken to examine the rates of readmission, recurrent AHRF, and death following discharge and the risk factors associated with them. Methods: A cohort of COPD patients with AHRF who survived after treatment with NIV in a respiratory high dependency unit was prospectively followed from July 2001 to October 2002. The times to readmission, first recurrent AHRF, and death were recorded and analysed against potential risk factors collected during the index admission. Results: One hundred and ten patients (87 men) of mean (SD) age 73.2 (7.6) years survived AHRF after NIV during the study period. One year after discharge 79.9% had been readmitted, 63.3% had another life threatening event, and 49.1% had died. Survivors spent a median of 12% of the subsequent year in hospital. The number of days in hospital in the previous year (p = 0.016) and a low Katz score (p = 0.018) predicted early readmission; home oxygen use (p = 0.002), APACHE II score (p = 0.006), and a lower body mass index (p = 0.041) predicted early recurrent AHRF or death; the MRC dyspnoea score (p<0.001) predicted early death. Conclusions: COPD patients with AHRF who survive following treatment with NIV have a high risk of readmission and life threatening events. Further studies are urgently needed to devise strategies to reduce readmission and life threatening events in this group of patients.",,"['Chu, C', 'Chan, V', 'Lin, A', 'Wong, I', 'Leung, W', 'Lai, C']",,,,
,PMC,Effect of integrated traditional Chinese and Western medicine on SARS: A review of clinical evidence,http://dx.doi.org/10.3748/wjg.v10.i23.3500,PMC4576235,,,"AIM: To assess the possible effect of integrated traditional Chinese and Western medicine on severe acute respiratory syndromes. METHODS: The current available randomized controlled trials of integrated traditional Chinese and Western medicine on SARS were identified through systematically searching literature in any languages or any types of publications. Additional studies of gray literature were also collected. The quality of studies was evaluated by two investigators independently based largely on the quality criteria specified CONSORT. Statistical analysis of the results was performed using RevMan 4.2.0 software developed by the Cochrane Collaboration. RESULTS: Six studies (n = 366) fulfilling the inclusion criteria were found, of which the quality of one study was graded as B, the remaining five were graded as C. Two studies were performed with meta-analysis, the other four studies existed some heterogeneity for which meta-analysis could not be performed, a significant effect on lung infiltrate absorption was found in the treatment groups of these two studies [RR 6.68, 95%CI (2.93, 15.24), P < 0.01], there was no significant differences between the mortality [RR 0.86, 95%CI (0.22, 3.29), P = 0.82] and the average dosage of corticosteroid [WMD -39.65, 95%CI (-116.84, 37.54), P = 0.31]. The other three studies also showed significant differences in infiltrate absorption, including national drug No. 2. 3. 4 in combination with Western medicine [RR 5.45, 95%CI (1.54, 19.26)], compound formulas NO. 1 combined with Western medicine [WMD 0.24, 95%CI (0.02, 0.46)], compound formulas combined with Western medicine [RR 8.06, 95%CI (0.40, 163.21)]. Kangfeidian No.4 in combination with Western medicine had no significant effect on symptom improvement such as loss of dyspnea and cough [RR 1.50, 95%CI (0.41, 5.43)] and [RR 1.29, 95%CI (0.30, 5.43)]. CONCLUSION: Integrated traditional Chinese and Western medicines has some positive effects on lung infiltrate absorption in SARS patients, and is recommended as an adjunct treatment for SARS. However, its effect on SARS requires further careful study due to limited available randomized control trials.",,"['Zhang, Ming-Ming', 'Liu, Xue-Mei', 'He, Lin']",,,,
,PMC,Plasma proteome of severe acute respiratory syndrome analyzed by two-dimensional gel electrophoresis and mass spectrometry,http://dx.doi.org/10.1073/pnas.0407992101,PMC535397,,,"We have investigated the plasma proteome by using 2D gel electrophoresis and MS from patients with severe acute respiratory syndrome (SARS). A complete proteomic analysis was performed on four patients with SARS in different time courses, and a total of 38 differential spots were selected for protein identification. Most of the proteins identified are acute phase proteins, and their presence represents the consequence of serial cascades initiated by SARS-coronavirus infection. There are several proteins that have never been identified in plasma before using 2D gel electrophoresis, among which peroxiredoxin II was chosen for further study by analyzing additional 20 plasma samples from patients with probable and suspected SARS and patients with fever, respectively. The results showed that the level of plasma peroxiredoxin II in patients with SARS is significantly high and could be secreted by T cells. Taken together, our findings indicate that active innate immune responses, along with the oxidation-associated injuries, may play a major role in the pathogenesis of SARS.",,"['Chen, Jenn-Han', 'Chang, Yu-Wang', 'Yao, Chen-Wen', 'Chiueh, Tzong-Shi', 'Huang, Su-Chin', 'Chien, Ko-Yi', 'Chen, An', 'Chang, Feng-Yee', 'Wong, Chi-Huey', 'Chen, Yu-Ju']",,,,
,PMC,"The protein structures that shape caspase activity, specificity, activation and inhibition",http://dx.doi.org/10.1042/BJ20041142,PMC1134104,,,"The death morphology commonly known as apoptosis results from a post-translational pathway driven largely by specific limited proteolysis. In the last decade the structural basis for apoptosis regulation has moved from nothing to ‘quite good’, and we now know the fundamental structures of examples from the initiator phase, the pre-mitochondrial regulator phase, the executioner phase, inhibitors and their antagonists, and even the structures of some substrates. The field is as well advanced as the best known of proteolytic pathways, the coagulation cascade. Fundamentally new mechanisms in protease regulation have been disclosed. Structural evidence suggests that caspases have an unusual catalytic mechanism, and that they are activated by apparently unrelated events, depending on which position in the apoptotic pathway they occupy. Some naturally occurring caspase inhibitors have adopted classic inhibition strategies, but other have revealed completely novel mechanisms. All of the structural and mechanistic information can, and is, being applied to drive therapeutic strategies to combat overactivation of apoptosis in degenerative disease, and underactivation in neoplasia. We present a comprehensive review of the caspases, their regulators and inhibitors from a structural and mechanistic point of view, and with an aim to consolidate the many threads that define the rapid growth of this field.",,"['Fuentes-Prior, Pablo', 'Salvesen, Guy\xa0S.']",,,,
,PMC,The impact of SARS on a tertiary care pediatric emergency department,http://dx.doi.org/10.1503/cmaj.1031257,PMC527337,,,"BACKGROUND: The Greater Toronto Area (GTA) was considered a “hot zone” for severe acute respiratory syndrome (SARS) in 2003. In accordance with mandated city-wide infection control measures, the Hospital for Sick Children (HSC) drastically reduced all services while maintaining a fully operational emergency department. Because of the GTA health service suspensions and the overlap of SARS-like symptoms with many common childhood illnesses, this introduced the potential for a change in the volumes of patients visiting the emergency department of the only regional tertiary care children's hospital. METHODS: We compared HSC emergency department patient volumes, admission rates and length of stay in the emergency department in the baseline years of 2000–2002 (non-SARS years) with those in 2003 (SARS year). The data from the prior years were modeled as a time series. Using an interrupted time series analysis, we compared the 2003 data for the periods before, during and after the SARS periods with the modeled data for significant differences in the 3 aforementioned outcomes of interest. RESULTS: Compared with the 2000–2002 data, we found no differences in visits, admission rates or length of stay in the pre-SARS period in 2003. There were significant decreases in visits and length of stay (p < 0.001) and increases in admission rates (p < 0.001) during the periods in 2003 when there were new and active cases of SARS in the GTA. All 3 outcomes returned to expected estimates coincident with the absence of SARS cases from September to December 2003. INTERPRETATION: During the SARS outbreak in the GTA, the HSC emergency department experienced significantly reduced volumes of patients with low-acuity complaints. This gives insight into utilization rates of a pediatric emergency department during a time when there was additional perceived risk in using emergency department services and provides a foundation for emergency department preparedness policies for SARS-like public health emergencies.",,"['Boutis, Kathy', 'Stephens, Derek', 'Lam, Kelvin', 'Ungar, Wendy J.', 'Schuh, Suzanne']",,,,
,PMC,Initial viral load and the outcomes of SARS,http://dx.doi.org/10.1503/cmaj.1040398,PMC527336,,,"BACKGROUND: Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus. It may progress to respiratory failure, and a significant proportion of patients die. Preliminary data suggest that a high viral load of the SARS coronavirus is associated with adverse outcomes in the intensive care unit, but the relation of viral load to survival is unclear. METHODS: We prospectively studied an inception cohort of 133 patients with virologically confirmed SARS who were admitted to 2 general acute care hospitals in Hong Kong from Mar. 24 to May 4, 2003. The patients were followed until death or for a minimum of 90 days. We used Cox proportional hazard modelling to analyze potential predictors of survival recorded at the time of presentation, including viral load from nasopharyngeal specimens (measured by quantitative reverse transcriptase polymerase chain reaction [PCR] of the SARS-associated coronavirus). RESULTS: Thirty-two patients (24.1%) met the criteria for acute respiratory distress syndrome, and 24 patients (18.0%) died. The following baseline factors were independently associated with worse survival: older age (61–80 years) (adjusted hazard ratio [HR] 5.24, 95% confidence interval [CI] 2.03–13.53), presence of an active comorbid condition (adjusted HR 3.36, 95% CI 1.44–7.82) and higher initial viral load of SARS coronavirus, according to quantitative PCR of nasopharyngeal specimens (adjusted HR 1.21 per log(10) increase in number of RNA copies per millilitre, 95% CI 1.06–1.39). INTERPRETATION: We found preliminary evidence that higher initial viral load is independently associated with worse prognosis in SARS. Mortality data for patients with SARS should be interpreted in light of age, comorbidity and viral load. These considerations will be important in future studies of SARS.",,"['Chu, Chung-Ming', 'Poon, Leo L.M.', 'Cheng, Vincent C.C.', 'Chan, Kin-Sang', 'Hung, Ivan F.N.', 'Wong, Maureen M.L.', 'Chan, Kwok-Hung', 'Leung, Wah-Shing', 'Tang, Bone S.F.', 'Chan, Veronica L.', 'Ng, Woon-Leung', 'Sim, Tiong-Chee', 'Ng, Ping-Wing', 'Law, Kin-Ip', 'Tse, Doris M.W.', 'Peiris, Joseph S.M.', 'Yuen, Kwok-Yung']",,,,
,PMC,SARS outbreak in the Greater Toronto Area: the emergency department experience,http://dx.doi.org/10.1503/cmaj.1031580,PMC527332,,,,,"['Borgundvaag, Bjug', 'Ovens, Howard', 'Goldman, Brian', 'Schull, Michael', 'Rutledge, Tim', 'Boutis, Kathy', 'Walmsley, Sharon', 'McGeer, Allison', 'Rachlis, Anita', 'Farquarson, Carolyn']",,,,
,PMC,Highlights of this issue,,PMC527299,,,,,,,,,
,PMC,Systematic analysis of bicistronic reporter assay data,http://dx.doi.org/10.1093/nar/gnh157,PMC534638,,,"Bicistronic reporter assay systems have become a mainstay of molecular biology. While the assays themselves encompass a broad range of diverse and unrelated experimental protocols, the numerical data garnered from these experiments often have similar statistical properties. In general, a primary dataset measures the paired expression of two internally controlled reporter genes. The expression ratio of these two genes is then normalized to an external control reporter. The end result is a ‘ratio of ratios’ that is inherently sensitive to propagation of the error contributed by each of the respective numerical components. The statistical analysis of this data therefore requires careful handling in order to control for the propagation of error and its potentially misleading effects. A careful survey of the literature found no consistent method for the statistical analysis of data generated from these important and informative assay systems. In this report, we present a detailed statistical framework for the systematic analysis of data obtained from bicistronic reporter assay systems. Specifically, a dual luciferase reporter assay was employed to measure the efficiency of four programmed −1 frameshift signals. These frameshift signals originate from the L-A virus, the SARS-associated Coronavirus and computationally identified frameshift signals from two Saccharomyces cerevisiae genes. Furthermore, these statistical methods were applied to prove that the effects of anisomycin on programmed −1 frameshifting are statistically significant. A set of Microsoft Excel spreadsheets, which can be used as templates for data generated by dual reporter assay systems, and an online tutorial are available at our website (http://dinmanlab.umd.edu/statistics). These spreadsheets could be easily adapted to any bicistronic reporter assay system.",,"['Jacobs, Jonathan L.', 'Dinman, Jonathan D.']",,,,
,PMC,Modelling strategies for minimizing the impact of an imported exotic infection.,,PMC1691871,,,"The global epidemic of severe acute respiratory syndrome (SARS) in 2003 demonstrated the need to determine control strategies for exotic infections. The prior determination of such strategies, and the use of mathematical models to assist this, is hampered by the obvious lack of data. We propose an integral equation model of Kermack-McKendrick type that may be used to compare strategies based on the isolation of infectious individuals. The model structures the incidence of infection according to the location of an infected individual at exposure, and requires knowledge of the infectivity kernel and the initial rate of exponential increase of cases. The model's use in the design of strategies to minimize the risk of SARS in a previously unexposed community is demonstrated.",,"Roberts, M. G.",,,,
,PMC,Coroner criticised over conduct of SARS inquest,,PMC529389,,,,,"Parry, Jane",,,,
,PMC,Learning from low income countries: what are the lessons?: Sources of information should focus on developing countries,,PMC527743,,,,,"['Newell, James N', 'Furber, Andrew S']",,,,
,PMC,In brief,,PMC527677,,,,,,,,,
,PMC,Health and economic benefits of an accelerated program of research to combat global infectious diseases,http://dx.doi.org/10.1503/cmaj.1041634,PMC524952,,,,,,,,,
,PMC,SARS silver lining: a renewal of public health,http://dx.doi.org/10.1503/cmaj.1041624,PMC524940,,,,,"Sornberger, Joe",,,,
,PMC,Transgenic mice expressing a soluble form of porcine nectin-1/herpesvirus entry mediator C as a model for pseudorabies-resistant livestock,http://dx.doi.org/10.1073/pnas.0405816101,PMC528950,,,"An approach to genetically engineered resistance to pseudorabies virus (PRV) infection was examined by using a transgene encoding a soluble form of nectin-1, also known as herpesvirus entry mediator C. Nectin-1 is an α-herpesvirus receptor that binds to virion glycoprotein D. Nectin-1 mediates entry of PRV, herpes simplex virus types 1 and 2, and bovine herpesvirus type 1. To assess the antiviral potential of an ectopic expression of the nectin-1 ectodomain in vivo, six transgenic mouse lines expressing a soluble form of nectin-1, consisting of an extracellular domain of porcine nectin-1 and the Fc portion of human IgG1, were generated. All of the transgenic mouse lines showed nearly complete resistance to PRV infection by means of both i.p. and intranasal routes. These results suggest that the introduction into farm animals of a transgene encoding a soluble form of nectin-1 would offer a potent biological approach to generating α-herpesvirus-resistant livestock.",,"['Ono, Etsuro', 'Amagai, Keiko', 'Taharaguchi, Satoshi', 'Tomioka, Yukiko', 'Yoshino, Saori', 'Watanabe, Yuki', 'Cherel, Pierre', 'Houdebine, Louis-Marie', 'Adam, Micheline', 'Eloit, Marc', 'Inobe, Manabu', 'Uede, Toshimitsu']",,,,
,PMC,Modelling strategies for controlling SARS outbreaks.,http://dx.doi.org/10.1098/rspb.2004.2800,PMC1691853,,,"Severe acute respiratory syndrome (SARS), a new, highly contagious, viral disease, emerged in China late in 2002 and quickly spread to 32 countries and regions causing in excess of 774 deaths and 8098 infections worldwide. In the absence of a rapid diagnostic test, therapy or vaccine, isolation of individuals diagnosed with SARS and quarantine of individuals feared exposed to SARS virus were used to control the spread of infection. We examine mathematically the impact of isolation and quarantine on the control of SARS during the outbreaks in Toronto, Hong Kong, Singapore and Beijing using a deterministic model that closely mimics the data for cumulative infected cases and SARS-related deaths in the first three regions but not in Beijing until mid-April, when China started to report data more accurately. The results reveal that achieving a reduction in the contact rate between susceptible and diseased individuals by isolating the latter is a critically important strategy that can control SARS outbreaks with or without quarantine. An optimal isolation programme entails timely implementation under stringent hygienic precautions defined by a critical threshold value. Values below this threshold lead to control, but those above are associated with the incidence of new community outbreaks or nosocomial infections, a known cause for the spread of SARS in each region. Allocation of resources to implement optimal isolation is more effective than to implement sub-optimal isolation and quarantine together. A community-wide eradication of SARS is feasible if optimal isolation is combined with a highly effective screening programme at the points of entry.",,"['Gumel, Abba B.', 'Ruan, Shigui', 'Day, Troy', 'Watmough, James', 'Brauer, Fred', 'van den Driessche, P.', 'Gabrielson, Dave', 'Bowman, Chris', 'Alexander, Murray E.', 'Ardal, Sten', 'Wu, Jianhong', 'Sahai, Beni M.']",,,,
,PMC,Global spending on health research still skewed towards wealthy nations,,PMC526148,,,,,"White, Caroline",,,,
,PMC,Monitoring global health: time for new solutions,,PMC526127,,,"Improved global health monitoring requires new technologies and methods, strengthened national capacity, norms and standards, and gold standard global reporting. The World Health Organization's many functions limit its capacity for global reporting, and a new global health monitoring organisation is needed to provide independent gold standard health information to the world",,"['Murray, Christopher J L', 'Lopez, Alan D', 'Wibulpolprasert, Suwit']",,,,
,PMC,Research and Development of New Vaccines Against Infectious Diseases,,PMC1448562,,,"Infectious diseases are responsible for approximately 25% of global mortality, especially in children aged younger than 5 years. Much of the burden of infectious diseases could be alleviated if appropriate mechanisms could be put in place to ensure access for all children to basic vaccines, regardless of geographical location or economic status. In addition, new safe and effective vaccines should be developed for a variety of infections against which no effective preventive intervention measure is either available or practical. The public, private, and philanthropic sectors need to join forces to ensure that these new or improved vaccines are fully developed and become accessible to the populations in need as quickly as possible.",,"['Kieny, Marie Paule', 'Excler, Jean-Louis', 'Girard, Marc']",,,,
,PMC,Perspectives on emerging zoonotic disease research and capacity building in Canada,,PMC2094993,,,"Zoonoses are fundamental determinants of community health. Preventing, identifying and managing these infections must be a central public health focus. Most current zoonoses research focuses on the interface of the pathogen and the clinically ill person, emphasizing microbial detection, mechanisms of pathogenicity and clinical intervention strategies, rather than examining the causes of emergence, persistence and spread of new zoonoses. There are gaps in the understanding of the animal determinants of emergence and the capacity to train highly qualified individuals; these are major obstacles to preventing new disease threats. The ability to predict the emergence of zoonoses and their resulting public health and societal impacts are hindered when insufficient effort is devoted to understanding zoonotic disease epidemiology, and when zoonoses are not examined in a manner that yields fundamental insight into their origin and spread. Emerging infectious disease research should rest on four pillars: enhanced communications across disciplinary and agency boundaries; the assessment and development of surveillance and disease detection tools; the examination of linkages between animal health determinants of human health outcomes; and finally, cross-disciplinary training and research. A national strategy to predict, prevent and manage emerging diseases must have a prominent and explicit role for veterinary and biological researchers. An integrated health approach would provide decision makers with a firmer foundation from which to build evidence-based disease prevention and control plans that involve complex human/animal/environmental systems, and would serve as the foundation to train and support the new cadre of individuals ultimately needed to maintain and apply research capacity in this area.",,"['Stephen, Craig', 'Artsob, Harvey', 'Bowie, William R', 'Drebot, Michael', 'Fraser, Erin', 'Leighton, Ted', 'Morshed, Muhammad', 'Ong, Corinne', 'Patrick, David']",,,,
,PMC,Severe acute respiratory syndrome: What have we learned two years later?,,PMC2094990,,,,,"['Johnston, Lynn B', 'Conly, John M']",,,,
,PMC,Use of Viral Lysate Antigen Combined with Recombinant Protein in Western Immunoblot Assay as Confirmatory Test for Serodiagnosis of Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1128/CDLI.11.6.1148-1153.2004,PMC524763,,,"A Western immunoblot assay for confirmatory serodiagnosis of severe acute respiratory syndrome (SARS) was developed utilizing viral lysate antigens combined with a recombinant nucleocapsid protein, GST-N (glutathione S-transferase-nucleocapsid) of the SARS coronavirus (SARS-CoV). The viral lysate antigens were separated by electrophoresis and transblotted onto nitrocellulose membranes. The resultant membrane was subsequently added with the GST-N recombinant protein at a specific location. The positions of bands corresponding to some of the structural proteins immobilized on the membrane were then located and verified with mouse or rabbit antisera specific to the respective proteins. The Western immunoblot assay was able to detect antibodies to SARS-CoV in all 40 serum specimens from SARS patients and differentiate the SARS-positive samples from those of the healthy donor or non-SARS patient controls (150 samples) when set criteria were followed. In addition, when the immunoblot was used to test samples considered falsely positive by an in-house-developed SARS-specific enzyme-linked immunosorbent assay, band patterns different from those with samples from SARS patients were obtained.",,"['Guan, Ming', 'Chen, Hsiao Ying', 'Tan, Phuay Heng', 'Shen, Shuo', 'Goh, Phuay-Yee', 'Tan, Yee-Joo', 'Pang, Peow Hoon', 'Lu, Yang', 'Fong, Priscilla Yiquan', 'Chin, Daria']",,,,
,PMC,Specific Immunoglobulin G Antibody Detected in Umbilical Blood and Amniotic Fluid from a Pregnant Woman Infected by the Coronavirus Associated with Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1128/CDLI.11.6.1182-1184.2004,PMC524739,,,"Specific immunoglobulin G antibody for severe acute respiratory syndrome (SARS) coronavirus was detected in maternal blood, umbilical blood, and amniotic fluid from a pregnant SARS patient. Potential protection of fetus from infection was suggested.",,"['Jiang, Xiugao', 'Gao, Xing', 'Zheng, Han', 'Yan, Meiying', 'Liang, Weili', 'Shao, Zhujun', 'Li, Wei', 'Zhang, Enmin', 'Hu, Yuan', 'Hai, Rong', 'Yu, Dongzheng', 'Kan, Biao', 'Xu, Jianguo']",,,,
,PMC,Exceptional Matters: clinical research from bedside to bench,http://dx.doi.org/10.7861/clinmedicine.4-6-551,PMC4951994,,,,,"Peters, Keith",,,,
,PMC,The returned traveller,http://dx.doi.org/10.7861/clinmedicine.4-6-505,PMC4951985,,,,,"Ellis, Christopher",,,,
,PMC,Fashion of the times,http://dx.doi.org/10.1038/sj.embor.7400288,PMC1299183,,,"The emergence and evolution of new research fields is as much determined by scientific interest as it is by social, political and economic pressures",,"Weigmann, Katrin",,,,
,PMC,"SARS, the First Pandemic of the 21st Century",http://dx.doi.org/10.3201/eid1011.040797_02,PMC3329048,,NO-CC CODE,,2004 Nov,"['LeDuc, James W.', 'Barry, M. Anita']",Emerg Infect Dis,,,
,PMC,Infectious Diseases and Maternal Morbidity and Mortality,http://dx.doi.org/10.3201/eid1011.040624_05,PMC3329032,,NO-CC CODE,,2004 Nov,"['Finnegan, Loretta P.', 'Sheffield, Jeanne', 'Sanghvi, Harshad', 'Anker, Martha']",Emerg Infect Dis,,,
,PMC,Women and Infectious Disease—Chronic Disease Interactions,http://dx.doi.org/10.3201/eid1011.040623_14,PMC3329027,,NO-CC CODE,,2004 Nov,"[""O'Connor, Siobhán"", 'West, Sheila K.', 'Lorntz, Breyette', 'Vinicor, Frank', 'Jorgensen, Cynthia']",Emerg Infect Dis,,,
,PMC,Healthcare-related Infectious Diseases,http://dx.doi.org/10.3201/eid1011.040622_03,PMC3329010,,NO-CC CODE,,2004 Nov,"['Swanson, Naomi', 'Ross, Clara Sue', 'Fennelly, Kevin']",Emerg Infect Dis,,,
,PMC,Impact of a severe acute respiratory syndrome outbreak in the emergency department: an experience in Taiwan,http://dx.doi.org/10.1136/emj.2003.010678,PMC1726484,,,"Objectives: To evaluate the impact of a severe acute respiratory syndrome (SARS) outbreak in the emergency department (ED). Methods: Computerised records of all ED visits in January and May 2003 were analysed and compared, representing before and during the SARS epidemic respectively. Data were grouped into two categories. Group 1 was the indicators of impact on patients, including visitor's condition classification, number of patients that died on arrival (DOA), received cardiopulmonary resuscitation, underwent endotracheal intubation, needed mechanical ventilation, discharged against medical advice (AAD), died in the ED, and the admission rate to wards. Group 2 was the indicators of impact on the quality of medical care, including number of visits that returned within 72 hours (early returns), underwent chest radiography, upper abdomen sonography or computed tomography, and the length of stay. Results: There were 6650 and 3901 consecutive encounters in January and May 2003 respectively. There were significant differences on condition classifications (p = 0.000), increased rate of patients that underwent endotracheal intubation (p = 0.003), needed mechanical ventilation (p = 0.020), and admission (p = 0.000). The rate of AAD decreased significantly (p = 0.024). There was no significant difference on early returns, although the length of stay in the ED increased (p = 0.043). The number of visits that underwent chest radiological examination increased (p = 0.000) and upper abdomen sonography (p = 0.007) decreased significantly in May. Conclusions: SARS had an impact on the medical service system and decreased visits by 40% in the ED. Patients visiting the ED had more severe conditions than before. The impact of SARS on quality of medical care can be minimised when adequate infection control measures are applied.",,"['Chen, T', 'Lai, K', 'Chang, H']",,,,
,PMC,Palindromes in SARS and Other Coronaviruses,,PMC4066412,,,"With the identification of a novel coronavirus associated with the severe acute respiratory syndrome (SARS), computational analysis of its RNA genome sequence is expected to give useful clues to help elucidate the origin, evolution, and pathogenicity of the virus. In this paper, we study the collective counts of palindromes in the SARS genome along with all the completely sequenced coronaviruses. Based on a Markov-chain model for the genome sequence, the mean and standard deviation for the number of palindromes at or above a given length are derived. These theoretical results are complemented by extensive simulations to provide empirical estimates. Using a z score obtained from these mathematical and empirical means and standard deviations, we have observed that palindromes of length four are significantly underrepresented in all the coronaviruses in our data set. In contrast, length-six palindromes are significantly underrepresented only in the SARS coronavirus. Two other features are unique to the SARS sequence. First, there is a length-22 palindrome TCTTTAACAAGCTTGTTAAAGA spanning positions 25962–25983. Second, there are two repeating length-12 palindromes TTATAATTATAA spanning positions 22712–22723 and 22796–22807. Some further investigations into possible biological implications of these palindrome features are proposed.",,"['Chew, David S. H.', 'Choi, Kwok Pui', 'Heidner, Hans', 'Leung, Ming-Ying']",,,,
,PMC,Mapping of Antigenic Sites on the Nucleocapsid Protein of the Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JCM.42.11.5309-5314.2004,PMC525273,,,"Antigenic sites on the nucleocapsid (N) protein of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) were mapped by Pepscan analysis with overlapping peptides that span the N protein sequence. Two major immunodominant epitopes located in the C-terminal region (amino acids [aa] 362 to 412) and middle region (aa 153 to 178) reacted with more than 75% of sera from SARS patients. Several minor immunodominant epitopes were reactive with about 50% of the SARS sera. Antisera from mice immunized with inactivated SARS-CoV recognized the two major immunodominant epitopes and one antigenic site located adjacent to the N-terminal region (aa 76 to 101), which did not react with the sera from SARS patients. Several monoclonal antibodies against SARS-CoV bound to the N- or C-terminal antigenic sites. These results suggest that the above antigenic sites on the N protein are important in eliciting humoral immune response against SARS-CoV in humans and animals and can be used as antigens for developing diagnostic tests.",,"['He, Yuxian', 'Zhou, Yusen', 'Wu, Hao', 'Kou, Zhihua', 'Liu, Shuwen', 'Jiang, Shibo']",,,,
,PMC,Immunization with Modified Vaccinia Virus Ankara-Based Recombinant Vaccine against Severe Acute Respiratory Syndrome Is Associated with Enhanced Hepatitis in Ferrets,http://dx.doi.org/10.1128/JVI.78.22.12672-12676.2004,PMC525089,,,"Severe acute respiratory syndrome (SARS) caused by a newly identified coronavirus (SARS-CoV) is a serious emerging human infectious disease. In this report, we immunized ferrets (Mustela putorius furo) with recombinant modified vaccinia virus Ankara (rMVA) expressing the SARS-CoV spike (S) protein. Immunized ferrets developed a more rapid and vigorous neutralizing antibody response than control animals after challenge with SARS-CoV; however, they also exhibited strong inflammatory responses in liver tissue. Inflammation in control animals exposed to SARS-CoV was relatively mild. Thus, our data suggest that vaccination with rMVA expressing SARS-CoV S protein is associated with enhanced hepatitis.",,"['Weingartl, Hana', 'Czub, Markus', 'Czub, Stefanie', 'Neufeld, James', 'Marszal, Peter', 'Gren, Jason', 'Smith, Greg', 'Jones, Shane', 'Proulx, Roxanne', 'Deschambault, Yvonne', 'Grudeski, Elsie', 'Andonov, Anton', 'He, Runtao', 'Li, Yan', 'Copps, John', 'Grolla, Allen', 'Dick, Daryl', 'Berry, Jody', 'Ganske, Shelley', 'Manning, Lisa', 'Cao, Jingxin']",,,,
,PMC,The Severe Acute Respiratory Syndrome Coronavirus Nsp15 Protein Is an Endoribonuclease That Prefers Manganese as a Cofactor,http://dx.doi.org/10.1128/JVI.78.22.12218-12224.2004,PMC525082,,,"Nonstructural protein 15 (Nsp15) of the severe acute respiratory syndrome coronavirus (SARS-CoV) produced in Escherichia coli has endoribonuclease activity that preferentially cleaved 5′ of uridylates of RNAs. Blocking either the 5′ or 3′ terminus did not affect cleavage. Double- and single-stranded RNAs were both substrates for Nsp15 but with different kinetics for cleavage. Mn(2+) at 2 to 10 mM was needed for optimal endoribonuclease activity, but Mg(2+) and several other divalent metals were capable of supporting only a low level of activity. Concentrations of Mn(2+) needed for endoribonuclease activity induced significant conformation change(s) in the protein, as measured by changes in tryptophan fluorescence. A similar endoribonucleolytic activity was detected for the orthologous protein from another coronavirus, demonstrating that the endoribonuclease activity of Nsp15 may be common to coronaviruses. This work presents an initial biochemical characterization of a novel coronavirus endoribonuclease.",,"['Bhardwaj, Kanchan', 'Guarino, Linda', 'Kao, C. Cheng']",,,,
,PMC,The Nucleoprotein Is Required for Efficient Coronavirus Genome Replication,http://dx.doi.org/10.1128/JVI.78.22.12683-12688.2004,PMC525053,,,"The construction of a set of transmissible gastroenteritis coronavirus (TGEV)-derived replicons as bacterial artificial chromosomes is reported. These replicons were generated by sequential deletion of nonessential genes for virus replication, using a modified TGEV full-length cDNA clone containing unique restriction sites between each pair of consecutive genes. Efficient activity of TGEV replicons was associated with the presence of the nucleoprotein provided either in cis or in trans. TGEV replicons were functional in several cell lines, including the human cell line 293T, in which no or very low cytopathic effect was observed, and expressed high amounts of heterologous protein.",,"['Almazán, Fernando', 'Galán, Carmen', 'Enjuanes, Luis']",,,,
,PMC,Generation of Synthetic Severe Acute Respiratory Syndrome Coronavirus Pseudoparticles: Implications for Assembly and Vaccine Production,http://dx.doi.org/10.1128/JVI.78.22.12557-12565.2004,PMC525052,,,"The recently emerged severe acute respiratory syndrome coronavirus (SARS-CoV) contains four structural genes, two replicase-transcriptase open reading frames, and more than five potential genes of unknown function. Despite this relative simplicity, the molecular regulation of SARS-CoV replication and assembly is not understood. Here, we report that two viral genes, encoding the SARS-CoV membrane (M) and nucleocapsid (N) proteins, are necessary and sufficient for formation of virus-like particles. Expression vectors encoding these two proteins were synthesized by using preferred human codons. When M and N expression plasmids were cotransfected into human 293 renal epithelial cells, pseudoparticles formed readily. The addition of a third gene, encoding the spike (S) glycoprotein, facilitated budding of particles that contained a corona-like halo resembling SARS-CoV when examined by transmission electron microscopy, with a buoyant density characteristic of coronaviruses. Specific biochemical interactions of these proteins were also shown in vitro. The S, M, and N proteins of the SARS-CoV are, therefore, necessary and sufficient for pseudovirus assembly. These findings advance the understanding of the morphogenesis of SARS-CoV and enable the generation of safe, conformational mimetics of the SARS virus that may facilitate the development of vaccines and antiviral drugs.",,"['Huang, Yue', 'Yang, Zhi-yong', 'Kong, Wing-pui', 'Nabel, Gary J.']",,,,
,PMC,DC-SIGN and DC-SIGNR Interact with the Glycoprotein of Marburg Virus and the S Protein of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.78.21.12090-12095.2004,PMC523257,,,"The lectins DC-SIGN and DC-SIGNR can augment viral infection; however, the range of pathogens interacting with these attachment factors is incompletely defined. Here we show that DC-SIGN and DC-SIGNR enhance infection mediated by the glycoprotein (GP) of Marburg virus (MARV) and the S protein of severe acute respiratory syndrome coronavirus and might promote viral dissemination. SIGNR1, a murine DC-SIGN homologue, also enhanced infection driven by MARV and Ebola virus GP and could be targeted to assess the role of attachment factors in filovirus infection in vivo.",,"['Marzi, Andrea', 'Gramberg, Thomas', 'Simmons, Graham', 'Möller, Peggy', 'Rennekamp, Andrew J.', 'Krumbiegel, Mandy', 'Geier, Martina', 'Eisemann, Jutta', 'Turza, Nadine', 'Saunier, Bertrand', 'Steinkasserer, Alexander', 'Becker, Stephan', 'Bates, Paul', 'Hofmann, Heike', 'Pöhlmann, Stefan']",,,,
,PMC,Infection of Specific Dendritic Cells by CCR5-Tropic Human Immunodeficiency Virus Type 1 Promotes Cell-Mediated Transmission of Virus Resistant to Broadly Neutralizing Antibodies,http://dx.doi.org/10.1128/JVI.78.21.11980-11987.2004,PMC523246,,,"The tropism of human immunodeficiency virus type 1 for chemokine receptors plays an important role in the transmission of AIDS. Although CXCR4-tropic virus is more cytopathic for T cells, CCR5-tropic strains are transmitted more frequently in humans for reasons that are not understood. Phenotypically immature myeloid dendritic cells (mDCs) are preferentially infected by CCR5-tropic virus, in contrast to mature mDCs, which are not susceptible to infection but instead internalize virus into a protected intracellular compartment and enhance the infection of T cells. Here, we define a mechanism to explain preferential transmission of CCR5-tropic viruses based on their interaction with mDCs and sensitivity to neutralizing antibodies. Infected immature mDCs differentiated normally and were found to enhance CCR5-tropic but not CXCR4-tropic virus infection of T cells even in the continuous presence of neutralizing antibodies. Infectious synapses also formed normally in the presence of such antibodies. Infection of immature mDCs by CCR5-tropic virus can therefore establish a pool of infected cells that can efficiently transfer virus at the same time that they protect virus from antibody neutralization. This property of DCs may enhance infection, contribute to immune evasion, and could provide a selective advantage for CCR5-tropic virus transmission.",,"['Ganesh, Lakshmanan', 'Leung, Kwanyee', 'Loré, Karin', 'Levin, Reuven', 'Panet, Amos', 'Schwartz, Owen', 'Koup, Richard A.', 'Nabel, Gary J.']",,,,
,PMC,Intracellular Localization and Protein Interactions of the Gene 1 Protein p28 during Mouse Hepatitis Virus Replication,http://dx.doi.org/10.1128/JVI.78.21.11551-11562.2004,PMC523235,,,"Coronaviruses encode the largest replicase polyprotein of any known positive-strand RNA virus. Replicase protein precursors and mature products are thought to mediate the formation and function of viral replication complexes on the surfaces of intracellular double-membrane vesicles. However, the functions of only a few of these proteins are known. For the coronavirus mouse hepatitis virus (MHV), the first proteolytic processing event of the replicase polyprotein liberates an amino-terminal 28-kDa product (p28). While previous biochemical studies have suggested that p28 is associated with viral replication complexes, the intracellular localization and interactions of p28 with other proteins during the course of MHV replication have not been defined. We used immunofluorescence confocal microscopy to show that p28 localizes to viral replication complexes in the cytoplasm during early times postinfection. However, at late times postinfection, p28 localizes to sites of M accumulation distinct from the replication complex. Furthermore, by yeast two-hybrid and coimmunoprecipitation analyses, we demonstrate that p28 specifically binds to p10 and p15, two coronavirus replicase proteins of unknown function. Deletion mutagenesis experiments determined that the carboxy terminus of p28 is not required for its interactions with p10 and p15. These results suggest that p28 may play a part at the replication complex by interacting with p10 and p15. Moreover, our findings highlight a potential role for p28 at virion assembly sites.",,"['Brockway, Sarah M.', 'Lu, Xiao Tao', 'Peters, Timothy R.', 'Dermody, Terence S.', 'Denison, Mark R.']",,,,
,PMC,Minisymposium 7,,PMC1757874,,,,,,,,,
,PMC,Novel application of sRNA: Stimulation of ribosomal frameshifting,http://dx.doi.org/10.1261/rna.7139704,PMC1370657,,,"Small RNAs play an important role in regulation of gene expression in eukaryotic and eubacterial cells by modulating gene expression both at the level of transcription and translation. Here, we show that short complementary RNAs can also affect gene expression by stimulating ribosomal frameshifting in vitro. This finding has important implications for understanding the process of ribosomal frameshifting and for the potential application of small RNAs in the treatment of diseases that are due to frameshift mutations.",,"['OLSTHOORN, R.C.L.', 'LAURS, M.', 'SOHET, F.', 'HILBERS, C.W.', 'HEUS, H.A.', 'PLEIJ, C.W.A.']",,,,
,PMC,What happens to patients with respiratory disease when they fly?,http://dx.doi.org/10.1136/thx.2004.025940,PMC1746885,,,,,"['Coker, R', 'Partridge, M']",,,,
,PMC,Three distinct suppressors of RNA silencing encoded by a 20-kb viral RNA genome,http://dx.doi.org/10.1073/pnas.0404940101,PMC524217,,,"Viral infection in both plant and invertebrate hosts requires a virus-encoded function to block the RNA silencing antiviral defense. Here, we report the identification and characterization of three distinct suppressors of RNA silencing encoded by the ≈20-kb plus-strand RNA genome of citrus tristeza virus (CTV). When introduced by genetic crosses into plants carrying a silencing transgene, both p20 and p23, but not coat protein (CP), restored expression of the transgene. Although none of the CTV proteins prevented DNA methylation of the transgene, export of the silencing signal (capable of mediating intercellular silencing spread) was detected only from the F(1) plants expressing p23 and not from the CP- or p20-expressing F(1) plants, demonstrating suppression of intercellular silencing by CP and p20 but not by p23. Thus, intracellular and intercellular silencing are each targeted by a CTV protein, whereas the third, p20, inhibits silencing at both levels. Notably, CP suppresses intercellular silencing without interfering with intracellular silencing. The novel property of CP suggests a mechanism distinct to p20 and all of the other viral suppressors known to interfere with intercellular silencing and that this class of viral suppressors may not be consistently identified by Agrobacterium coinfiltration because it also induces RNA silencing against the infiltrated suppressor transgene. Our analyses reveal a sophisticated viral counter-defense strategy that targets the silencing antiviral pathway at multiple steps and may be essential for protecting CTV with such a large RNA genome from antiviral silencing in the perennial tree host.",,"['Lu, Rui', 'Folimonov, Alexey', 'Shintaku, Michael', 'Li, Wan-Xiang', 'Falk, Bryce W.', 'Dawson, William O.', 'Ding, Shou-Wei']",,,,
,PMC,CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus,http://dx.doi.org/10.1073/pnas.0403812101,PMC524836,,,"Angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV, the novel coronavirus that causes severe acute respiratory syndrome [Li, W. Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., et al. (2003) Nature 426, 450–454]. We have identified a different human cellular glycoprotein that can serve as an alternative receptor for SARS-CoV. A human lung cDNA library in vesicular stomatitis virus G pseudotyped retrovirus was transduced into Chinese hamster ovary cells, and the cells were sorted for binding of soluble SARS-CoV spike (S) glycoproteins, S(590) and S(1180). Clones of transduced cells that bound SARS-CoV S glycoprotein were inoculated with SARS-CoV, and increases in subgenomic viral RNA from 1–16 h or more were detected by multiplex RT-PCR in four cloned cell lines. Sequencing of the human lung cDNA inserts showed that each of the cloned cell lines contained cDNA that encoded human CD209L, a C-type lectin (also called L-SIGN). When the cDNA encoding CD209L from clone 2.27 was cloned and transfected into Chinese hamster ovary cells, the cells expressed human CD209L glycoprotein and became susceptible to infection with SARS-CoV. Immunohistochemistry showed that CD209L is expressed in human lung in type II alveolar cells and endothelial cells, both potential targets for SARS-CoV. Several other enveloped viruses including Ebola and Sindbis also use CD209L as a portal of entry, and HIV and hepatitis C virus can bind to CD209L on cell membranes but do not use it to mediate virus entry. Our data suggest that the large S glycoprotein of SARS-CoV may use both ACE2 and CD209L in virus infection and pathogenesis.",,"['Jeffers, Scott A.', 'Tusell, Sonia M.', 'Gillim-Ross, Laura', 'Hemmila, Erin M.', 'Achenbach, Jenna E.', 'Babcock, Gregory J.', 'Thomas, William D.', 'Thackray, Larissa B.', 'Young, Mark D.', 'Mason, Robert J.', 'Ambrosino, Donna M.', 'Wentworth, David E.', 'DeMartini, James C.', 'Holmes, Kathryn V.']",,,,
,PMC,In brief,,PMC523101,,,,,,,,,
,PMC,Rebuilding an Immune-Mediated Central Nervous System Disease: Weighing the Pathogenicity of Antigen-Specific versus Bystander T Cells(),,PMC5319420,,,"Although both self- and pathogen-specific T cells can participate in tissue destruction, recent studies have proposed that after viral infection, bystander T cells of an irrelevant specificity can bypass peptide-MHC restriction and contribute to undesired immunopathological consequences. To evaluate the importance of this mechanism of immunopathogenesis, we determined the relative contributions of Ag-specific and bystander CD8(+) T cells to the development of CNS disease. Using lymphocytic choriomeningitis virus (LCMV) as a stimulus for T cell recruitment into the CNS, we demonstrate that bystander CD8(+) T cells with an activated surface phenotype can indeed be recruited into the CNS over a chronic time window. These cells become anatomically positioned in the CNS parenchyma, and a fraction aberrantly acquires the capacity to produce the effector cytokine, IFN-β. However, when directly compared with their virus-specific counterparts, the contribution of bystander T cells to CNS damage was insignificant in nature (even when specifically activated). Although bystander T cells alone failed to cause tissue injury, transferring as few as 1000 naive LCMV-specific CD8(+) T cells into a restricted repertoire containing only bystander T cells was sufficient to induce immune-mediated pathology and reconstitute a fatal CNS disease. These studies underscore the importance of specific T cells in the development of immunopathology and subsequent disease. Because of highly restrictive constraints imposed by the host, it is more likely that specific, rather than nonspecific, bystander T cells are the active participants in T cell-mediated diseases that afflict humans.",,"['McGavern, Dorian B.', 'Truong, Phi']",,,,
,PMC,Forecast and control of epidemics in a globalized world,http://dx.doi.org/10.1073/pnas.0308344101,PMC524041,,,"The rapid worldwide spread of severe acute respiratory syndrome demonstrated the potential threat an infectious disease poses in a closely interconnected and interdependent world. Here we introduce a probabilistic model that describes the worldwide spread of infectious diseases and demonstrate that a forecast of the geographical spread of epidemics is indeed possible. This model combines a stochastic local infection dynamics among individuals with stochastic transport in a worldwide network, taking into account national and international civil aviation traffic. Our simulations of the severe acute respiratory syndrome outbreak are in surprisingly good agreement with published case reports. We show that the high degree of predictability is caused by the strong heterogeneity of the network. Our model can be used to predict the worldwide spread of future infectious diseases and to identify endangered regions in advance. The performance of different control strategies is analyzed, and our simulations show that a quick and focused reaction is essential to inhibiting the global spread of epidemics.",,"['Hufnagel, L.', 'Brockmann, D.', 'Geisel, T.']",,,,
,PMC,"Cross-scale interactions, nonlinearities, and forecasting catastrophic events",http://dx.doi.org/10.1073/pnas.0403822101,PMC523446,,,"Catastrophic events share characteristic nonlinear behaviors that are often generated by cross-scale interactions and feedbacks among system elements. These events result in surprises that cannot easily be predicted based on information obtained at a single scale. Progress on catastrophic events has focused on one of the following two areas: nonlinear dynamics through time without an explicit consideration of spatial connectivity [Holling, C. S. (1992) Ecol. Monogr. 62, 447–502] or spatial connectivity and the spread of contagious processes without a consideration of cross-scale interactions and feedbacks [Zeng, N., Neeling, J. D., Lau, L. M. & Tucker, C. J. (1999) Science 286, 1537–1540]. These approaches rarely have ventured beyond traditional disciplinary boundaries. We provide an interdisciplinary, conceptual, and general mathematical framework for understanding and forecasting nonlinear dynamics through time and across space. We illustrate the generality and usefulness of our approach by using new data and recasting published data from ecology (wildfires and desertification), epidemiology (infectious diseases), and engineering (structural failures). We show that decisions that minimize the likelihood of catastrophic events must be based on cross-scale interactions, and such decisions will often be counterintuitive. Given the continuing challenges associated with global change, approaches that cross disciplinary boundaries to include interactions and feedbacks at multiple scales are needed to increase our ability to predict catastrophic events and develop strategies for minimizing their occurrence and impacts. Our framework is an important step in developing predictive tools and designing experiments to examine cross-scale interactions.",,"['Peters, Debra P. C.', 'Pielke, Roger A.', 'Bestelmeyer, Brandon T.', 'Allen, Craig D.', 'Munson-McGee, Stuart', 'Havstad, Kris M.']",,,,
,PMC,Strategies and mechanisms for host and pathogen survival in acute and persistent viral infections,http://dx.doi.org/10.1073/pnas.0404758101,PMC521982,,,"Persistent viral infections causing serious diseases derive, primarily, from altered function of the immune system. Knowledge of the very complex composition and function of the innate and adaptive branches of the immune system is essential to understanding persistent infection. The best solution to the problem of persistent infection is by prevention using prophylactic vaccines. Hit and run viruses evade immune destruction by infecting new hosts and rarely persist. Hit and stay viruses evade immune control by sequestration, blockade of antigen presentation, cytokine escape, evasion of natural killer cell activities, escape from apoptosis, and antigenic change. Twelve prophylactic vaccines against hit and run agents exist, and there are only three vaccines against hit and stay viruses, all of which are of DNA composition. Several new vaccines against hit and stay viruses are feasible, but protective vaccines against RNA HIV and hepatitis C agents are highly unlikely, short of a major breakthrough. Therapeutic vaccines are very improbable without a magnitude of favorable new discoveries. In the meantime, antiviral chemotherapy, chemotherapy/prophylactic vaccination, and short interfering RNA silencing are worthy of intense investigation.",,"Hilleman, Maurice R.",,,,
,PMC,Rural Public Health Service Delivery: Promising New Directions,,PMC1448514,,,"I describe variations in the structure and in the practice of rural public health and how rural communities meet the challenges of current public health practice, including primary methods of service delivery and partnership development. I present examples of promising models for the creation of rural public health capacity—the ability of local health departments to carry out core public health responsibilities.",,"Berkowitz, Bobbie",,,,
,PMC,Immunological response to Mycobacterium avium subsp. paratuberculosis in chickens,,PMC1111362,,,"Enzyme-linked immunosorbent assay (ELISA) and culture are 2 common diagnostic tests for detecting Mycobacterium avium subsp. paratuberculosis (Map) in Johne’s disease, but they are not as sensitive as polymerase chain reaction (PCR). However, inhibitors can coextract with the target DNA and cause interference in PCR. Development of an immune capture assay followed by PCR amplification can alleviate this problem. In this study, we were able to induce an immune response in chickens using heat or formalin inactivated Map. The purified immunoglobulin (Ig)Y has a molecular weight of 160 kDa. The titers were at 1:6400 and 1:12 800 at weeks 5 to 6 and 8 to 9, respectively, as determined by the IDEXX modified ELISA kit for Johne’s disease. The IgY produced from inactivated bacterial cells had no effect on its ability to recognize live Map cells as illustrated by immunofluorescence assay and immune capture PCR results.",,"['Chui, Linda W.', 'King, Robin', 'Chow, Eva Y.W.', 'Sim, Jeong']",,,,
,PMC,Epidemiologic Background of Hand Hygiene and Evaluation of the Most Important Agents for Scrubs and Rubs,http://dx.doi.org/10.1128/CMR.17.4.863-893.2004,PMC523567,,,"The etiology of nosocomial infections, the frequency of contaminated hands with the different nosocomial pathogens, and the role of health care workers' hands during outbreaks suggest that a hand hygiene preparation should at least have activity against bacteria, yeasts, and coated viruses. The importance of efficacy in choosing the right hand hygiene product is reflected in the new Centers for Disease Control and Prevention guideline on hand hygiene (J. M. Boyce and D. Pittet, Morb. Mortal. Wkly. Rep. 51:1-45, 2002). The best antimicrobial efficacy can be achieved with ethanol (60 to 85%), isopropanol (60 to 80%), and n-propanol (60 to 80%). The activity is broad and immediate. Ethanol at high concentrations (e.g., 95%) is the most effective treatment against naked viruses, whereas n-propanol seems to be more effective against the resident bacterial flora. The combination of alcohols may have a synergistic effect. The antimicrobial efficacy of chlorhexidine (2 to 4%) and triclosan (1 to 2%) is both lower and slower. Additionally, both agents have a risk of bacterial resistance, which is higher for chlorhexidine than triclosan. Their activity is often supported by the mechanical removal of pathogens during hand washing. Taking the antimicrobial efficacy and the mechanical removal together, they are still less effective than the alcohols. Plain soap and water has the lowest efficacy of all. In the new Centers for Disease Control and Prevention guideline, promotion of alcohol-based hand rubs containing various emollients instead of irritating soaps and detergents is one strategy to reduce skin damage, dryness, and irritation. Irritant contact dermatitis is highest with preparations containing 4% chlorhexidine gluconate, less frequent with nonantimicrobial soaps and preparations containing lower concentrations of chlorhexidine gluconate, and lowest with well-formulated alcohol-based hand rubs containing emollients and other skin conditioners. Too few published data from comparative trials are available to reliably rank triclosan. Personnel should be reminded that it is neither necessary nor recommended to routinely wash hands after each application of an alcohol-based hand rub. Long-lasting improvement of compliance with hand hygiene protocols can be successful if an effective and accessible alcohol-based hand rub with a proven dermal tolerance and an excellent user acceptability is supplied, accompanied by education of health care workers and promotion of the use of the product.",,"['Kampf, Günter', 'Kramer, Axel']",,,,
,PMC,When even the 'best-laid' plans go wrong,http://dx.doi.org/10.1038/sj.embor.7400257,PMC1299213,,,Strategic risk communication for new and emerging risks,,"McComas, Katherine",,,,
,PMC,The consequences of fear,http://dx.doi.org/10.1038/sj.embor.7400228,PMC1299209,,,Our modern world is a risky place and evokes many well-founded fears. But these fears themselves create a new risk for our health and well-being that needs to be addressed,,"Ropeik, David",,,,
,PMC,Globalization and risks to health,http://dx.doi.org/10.1038/sj.embor.7400226,PMC1299207,,,"As borders disappear, people and goods are increasingly free to move, creating new challenges to global health. These cannot be met by national governments alone but must be dealt with instead by international organizations and agreements",,"['Pang, Tikki', 'Guindon, G. Emmanuel']",,,,
,PMC,Factors associated with transmission of severe acute respiratory syndrome among health-care workers in Singapore.,,PMC2870165,,,"Between 1 and 22 March 2003, a nosocomial outbreak of Severe Acute Respiratory Syndrome (SARS) occurred at the Communicable Disease Centre in Tan Tock Seng Hospital, Singapore, the national treatment and isolation facility for patients with SARS. A case-control study with 36 cases and 50 controls was conducted of factors associated with the transmission of SARS within the hospital. In univariate analysis, contact with respiratory secretions elevated the odds ratio to 6.9 (95 % CI 1.4-34.6, P= 0.02). Protection was conferred by hand washing (OR 0.06, 95% CI 0.007-0.5, P=0.03) and wearing of N95 masks (OR 0.1, 95% CI 0.03-0.4, P=0.001). Use of gloves and gowns had no effect. Multivariate analysis confirmed the strong role of contact with respiratory secretions (adjusted OR 21.8, 95 % CI 1.7 274.8, P=0.017). Both hand washing (adjusted OR 0.07, 95 % CI 0.008-0.66, P=0.02) and wearing of N95 masks (adjusted OR 0.1, 95% CI 0.02-0.86, P=0.04) remained strongly protective but gowns and gloves had no effect.",,"['Teleman, M. D.', 'Boudville, I. C.', 'Heng, B. H.', 'Zhu, D.', 'Leo, Y. S.']",,,,
,PMC,The epidemiology of the outbreak of severe acute respiratory syndrome (SARS) in Hong Kong--what we do know and what we don't.,,PMC2870163,,,"Severe acute respiratory syndrome (SARS) struck Hong Kong bitterly in the spring of 2003, infecting 1755 persons and claiming nearly 300 lives. The epidemic was introduced by travellers from southern China, where the disease had originated. It started in late February and lasted until early June. Two notable 'super-spreading' events were reported, one inside a teaching hospital and the other in a private housing estate. Other than in the super-spreading events, the infectivity in the community appeared to be low, and there were few, if any, asymptomatic or subclinical infections. Health-care workers were at particular risk and accounted for 22 % of all probable cases. The main modes of transmission were through droplet spread and close/direct contacts, but situations conducive to aerosol generation appeared to be associated with higher risk. Our review suggests that there are still many unknown factors concerning the mode of transmission and environmental risk that need to be clarified.",,"['Yu, I. T. S.', 'Sung, J. J. Y.']",,,,
,PMC,Longitudinal Study of Viruses Associated with Canine Infectious Respiratory Disease,http://dx.doi.org/10.1128/JCM.42.10.4524-4529.2004,PMC522361,,,"In this investigation a population of dogs at a rehoming center was monitored over a period of 2 years. Despite regular vaccination of incoming dogs against distemper, canine adenovirus type 2 (CAV-2), and canine parainfluenza virus (CPIV), respiratory disease was endemic. Tissue samples from the respiratory tract as well as paired serum samples were collected for analysis. The development of PCR assays for the detection of CPIV, canine adenovirus types 1 and 2, and canine herpesvirus (CHV) is described. Surprisingly, canine adenovirus was not detected in samples from this population, whereas 19.4% of tracheal and 10.4% of lung samples were positive for CPIV and 12.8% of tracheal and 9.6% of lung samples were positive for CHV. As reported previously, a novel canine respiratory coronavirus (CRCoV) was detected in this population (K. Erles, C. Toomey, H. W. Brooks, and J. Brownlie, Virology 310:216-223, 2003). Infections with CRCoV occurred mostly during the first week of a dog's stay at the kennel, whereas CPIV and CHV were detected at later time points. Furthermore, the evaluation of an enzyme-linked immunosorbent assay for detection of antibodies to CPIV and an immunofluorescence assay for detection of antibodies to CHV is described. This study shows that CPIV is present at kennels despite vaccination. In addition, other agents such as CHV and CRCoV may play a role in the pathogenesis of canine respiratory disease, whereas CAV-2 and canine distemper virus were not present in this population, indicating that their prevalence in the United Kingdom is low due to widespread vaccination of dogs.",,"['Erles, Kerstin', 'Dubovi, Edward J.', 'Brooks, Harriet W.', 'Brownlie, Joe']",,,,
,PMC,Isolation of Shiga Toxin-Producing Escherichia coli from a South American Camelid (Lama guanicoe) with Diarrhea,http://dx.doi.org/10.1128/JCM.42.10.4809-4811.2004,PMC522311,,,"Shiga toxin-producing Escherichia coli belonging to serotype O26:H11 was isolated from a 2-month-old guanaco with severe watery diarrhea. E. coli colonies carried the stx(1) and eae genes, showed localized adherence to HEp-2 cells, and produced enterohemolysin. A serological response to lipopolysaccharide O26 was observed at the onset of diarrhea.",,"['Mercado, E. C.', 'Rodríguez, S. M.', 'Elizondo, A. M.', 'Marcoppido, G.', 'Parreño, V.']",,,,
,PMC,Prospective Study of Human Metapneumovirus Infection in Children Less Than 3 Years of Age,http://dx.doi.org/10.1128/JCM.42.10.4632-4635.2004,PMC522293,,,"Most lower respiratory tract infections (LRTIs) in children under the age of 3 years are due to respiratory syncytial virus (RSV). Epidemiological, host, and viral factors eventually account for the severity of LRTIs, but they do not completely explain it. Human metapneumovirus (hMPV) was recently identified in children with LRTIs. In a population-based prospective multicenter study (the PRI.DE study, conducted in Germany over 2 years), we tested 3,369 nasopharyngeal secretions from children younger than 3 years of age with LRTIs for RSV A and B, influenza viruses (IVs) A and B, and parainfluenza viruses (PIVs) 1 to 3. Of the children requiring intensive care (n = 85), 18% had hMPV infections, and 60% of these children were infected with hMPV in combination with RSV. We did not detect hMPV in a randomly selected subset of RSV-positive nasopharyngeal secretions (n = 120) from children not requiring intensive care support. hMPV was detected in <1% of virus-negative samples from patients without intensive care support (n = 620). Our data support the hypothesis that coinfections with RSV and hMPV are more severe than infections with either RSV or hMPV alone, at least in children younger than 3 years of age.",,"['König, Brigitte', 'König, Wolfgang', 'Arnold, Ralf', 'Werchau, Herrmann', 'Ihorst, Gabriele', 'Forster, Johannes']",,,,
,PMC,"Detection of U.S., Lelystad, and European-Like Porcine Reproductive and Respiratory Syndrome Viruses and Relative Quantitation in Boar Semen and Serum Samples by Real-Time PCR",http://dx.doi.org/10.1128/JCM.42.10.4453-4461.2004,PMC522289,,,"Transmission of porcine reproductive and respiratory syndrome virus (PRRSV) via boar semen has been documented. Since semen is widely disseminated for artificial insemination and the virus can cause significant health and economic consequences, it is essential to have well-validated, rapid diagnostic techniques to detect and quantitate the virus for diagnostic and research purposes. Previously, boar semen was tested by a nested PCR (nPCR) assay which was compared to the “gold standard” swine bioassay. A correlation of 94% was observed, indicating that, most of the time, PCR detected infectious virus. Subsequently, a real-time PCR targeting the 3′ untranslated region of the PRRSV genome was compared with nPCR by testing 413 serum and semen samples from PRRSV-inoculated and control boars. There was 95% agreement between the results of the two tests, with the majority of samples with discordant results containing virus at the lower range of detection by the assays. The virus in all samples was quantitated by using a standard curve obtained by serial dilution of an in vitro transcript. By using the in vitro transcript, the lower limit of sensitivity was observed to be approximately 33 copies/ml. Reactivity with a panel of more than 100 PRRSV isolates from various geographical regions in the United States was also documented. No reactivity with nine nonrelated swine viruses was noted. A real-time PCR was also developed for the detection of the European Lelystad virus and the European-like PRRSV now found in the United States. In six of six PRRSV-inoculated boars, peak levels of viremia occurred at 5 days postinoculation (DPI) and were most consistently detectable throughout 22 DPI. In five of six boars, PRRSV was shed in semen for 0 to 2 days during the first 10 DPI; however, one of six boars shed the virus in semen through 32 DPI. Therefore, in general, the concentration and duration of PRRSV shedding in semen did not correlate with the quantity or duration of virus in serum. These differences warrant further studies into the factors that prevent viral replication in the reproductive tract.",,"['Wasilk, A.', 'Callahan, J. D.', 'Christopher-Hennings, J.', 'Gay, T. A.', 'Fang, Y.', 'Dammen, M.', 'Reos, M. E.', 'Torremorell, M.', 'Polson, D.', 'Mellencamp, M.', 'Nelson, E.', 'Nelson, W. M.']",,,,
,PMC,Avian influenza: a human pandemic threat?,http://dx.doi.org/10.1136/jech.2004.022079,PMC1763342,,,,,"Rezza, G.",,,,
,PMC,The morality of inclusion: A response to Duffy,http://dx.doi.org/10.1136/jme.2003.006403,PMC1733952,,,,,"Tsai, D",,,,
,PMC,WHO membership: the plight of Taiwan,http://dx.doi.org/10.1136/jme.2002.000794,PMC1733920,,,,,"Duffy, T",,,,
,PMC,Calling the Shots: Immunization Finance Policies and Practices,,PMC2568513,,,,,"Shurin, Paul A.",,,,
,PMC,Complement C3 and C5 play critical roles in traumatic brain cryoinjury: blocking effects on neutrophil extravasation by C5a receptor antagonist(),http://dx.doi.org/10.1016/j.jneuroim.2004.06.003,PMC4766842,,,"The role of complement components in traumatic brain injury is poorly understood. Here we show that secondary damage after acute cryoinjury is significantly reduced in C3(−/−) or C5(−/−) mice or in mice treated with C5a receptor antagonist peptides. Injury sizes and neutrophil extravasation were compared. While neutrophil density increased following traumatic brain injury in wild type (C57BL/6) mice, C3-deficient mice demonstrated lower neutrophil extravasation and injury sizes in the brain. RNase protection assay indicated that C3 contributes to the induction of brain inflammatory mediators, MIF, RANTES (CCL5) and MCP-1 (CCL2). Intracranial C3 injection induced neutrophil extravasation in injured brains of C3(−/−) mice suggesting locally produced C3 is important in brain inflammation. We show that neutrophil extravasation is significantly reduced in both C5(−/−) mice and C5a receptor antagonist treated cryoinjured mice suggesting that one of the possible mechanisms of C3 effect on neutrophil extravasation is mediated via downstream complement activation products such as C5a. Our data indicates that complement inhibitors may ameliorate traumatic brain injury.",,"['Sewell, Diane L.', 'Nacewicz, Brendon', 'Liu, Frances', 'Macvilay, Sinarack', 'Erdei, Anna', 'Lambris, John D.', 'Sandor, Matyas', 'Fabry, Zsuzsa']",,,,
,PMC,Efficient Replication of Severe Acute Respiratory Syndrome Coronavirus in Mouse Cells Is Limited by Murine Angiotensin-Converting Enzyme 2,http://dx.doi.org/10.1128/JVI.78.20.11429-11433.2004,PMC521845,,,"Replication of viruses in species other than their natural hosts is frequently limited by entry and postentry barriers. The coronavirus that causes severe acute respiratory syndrome (SARS-CoV) utilizes the receptor angiotensin-converting enzyme 2 (ACE2) to infect cells. Here we compare human, mouse, and rat ACE2 molecules for their ability to serve as receptors for SARS-CoV. We found that, compared to human ACE2, murine ACE2 less efficiently bound the S1 domain of SARS-CoV and supported less-efficient S protein-mediated infection. Rat ACE2 was even less efficient, at near background levels for both activities. Murine 3T3 cells expressing human ACE2 supported SARS-CoV replication, whereas replication was less than 10% as efficient in the same cells expressing murine ACE2. These data imply that a mouse transgenically expressing human ACE2 may be a useful animal model of SARS.",,"['Li, Wenhui', 'Greenough, Thomas C.', 'Moore, Michael J.', 'Vasilieva, Natalya', 'Somasundaran, Mohan', 'Sullivan, John L.', 'Farzan, Michael', 'Choe, Hyeryun']",,,,
,PMC,Resolution of Primary Severe Acute Respiratory Syndrome-Associated Coronavirus Infection Requires Stat1,http://dx.doi.org/10.1128/JVI.78.20.11416-11421.2004,PMC521834,,,"Intranasal inhalation of the severe acute respiratory syndrome coronavirus (SARS CoV) in the immunocompetent mouse strain 129SvEv resulted in infection of conducting airway epithelial cells followed by rapid clearance of virus from the lungs and the development of self-limited bronchiolitis. Animals resistant to the effects of interferons by virtue of a deficiency in Stat1 demonstrated a markedly different course following intranasal inhalation of SARS CoV, one characterized by replication of virus in lungs and progressively worsening pulmonary disease with inflammation of small airways and alveoli and systemic spread of the virus to livers and spleens.",,"['Hogan, Robert J.', 'Gao, Guangping', 'Rowe, Thomas', 'Bell, Peter', 'Flieder, Douglas', 'Paragas, Jason', 'Kobinger, Gary P.', 'Wivel, Nelson A.', 'Crystal, Ronald G.', 'Boyer, Julie', 'Feldmann, Heinz', 'Voss, Thomas G.', 'Wilson, James M.']",,,,
,PMC,Macaque Model for Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1128/JVI.78.20.11401-11404.2004,PMC521815,,,Rhesus and cynomolgus macaques were challenged with 10(7) PFU of a clinical isolate of the severe acute respiratory syndrome (SARS) coronavirus. Some of the animals developed a mild self-limited respiratory infection very different from that observed in humans with SARS. The macaque model as it currently exists will have limited utility in the study of SARS and the evaluation of therapies.,,"['Rowe, Thomas', 'Gao, Guangping', 'Hogan, Robert J.', 'Crystal, Ronald G.', 'Voss, Thomas G.', 'Grant, Rebecca L.', 'Bell, Peter', 'Kobinger, Gary P.', 'Wivel, Nelson A.', 'Wilson, James M.']",,,,
,PMC,Lentivirus-Mediated RNA Interference of DC-SIGN Expression Inhibits Human Immunodeficiency Virus Transmission from Dendritic Cells to T Cells,http://dx.doi.org/10.1128/JVI.78.20.10848-10855.2004,PMC521813,,,"In the early events of human immunodeficiency virus type 1 (HIV-1) infection, immature dendritic cells (DCs) expressing the DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) receptor capture small amounts of HIV-1 on mucosal surfaces and spread viral infection to CD4(+) T cells in lymph nodes (22, 34, 45). RNA interference has emerged as a powerful tool to gain insight into gene function. For this purpose, lentiviral vectors that express short hairpin RNA (shRNA) for the delivery of small interfering RNA (siRNA) into mammalian cells represent a powerful tool to achieve stable gene silencing. In order to interfere with DC-SIGN function, we developed shRNA-expressing lentiviral vectors capable of conditionally suppressing DC-SIGN expression. Selectivity of inhibition of human DC-SIGN and L-SIGN and chimpanzee and rhesus macaque DC-SIGN was obtained by using distinct siRNAs. Suppression of DC-SIGN expression inhibited the attachment of the gp120 envelope glycoprotein of HIV-1 to DC-SIGN transfectants, as well as transfer of HIV-1 to target cells in trans. Furthermore, shRNA-expressing lentiviral vectors were capable of efficiently suppressing DC-SIGN expression in primary human DCs. DC-SIGN-negative DCs were unable to enhance transfer of HIV-1 infectivity to T cells in trans, demonstrating an essential role for the DC-SIGN receptor in transferring infectious viral particles from DCs to T cells. The present system should have broad applications for studying the function of DC-SIGN in the pathogenesis of HIV as well as other pathogens also recognized by this receptor.",,"['Arrighi, Jean-François', 'Pion, Marjorie', 'Wiznerowicz, Maciej', 'Geijtenbeek, Teunis B.', 'Garcia, Eduardo', 'Abraham, Shahnaz', 'Leuba, Florence', 'Dutoit, Valérie', 'Ducrey-Rundquist, Odile', 'van Kooyk, Yvette', 'Trono, Didier', 'Piguet, Vincent']",,,,
,PMC,Small Molecules Blocking the Entry of Severe Acute Respiratory Syndrome Coronavirus into Host Cells,http://dx.doi.org/10.1128/JVI.78.20.11334-11339.2004,PMC521800,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) is the pathogen of SARS, which caused a global panic in 2003. We describe here the screening of Chinese herbal medicine-based, novel small molecules that bind avidly with the surface spike protein of SARS-CoV and thus can interfere with the entry of the virus to its host cells. We achieved this by using a two-step screening method consisting of frontal affinity chromatography-mass spectrometry coupled with a viral infection assay based on a human immunodeficiency virus (HIV)-luc/SARS pseudotyped virus. Two small molecules, tetra-O-galloyl-β-d-glucose (TGG) and luteolin, were identified, whose anti-SARS-CoV activities were confirmed by using a wild-type SARS-CoV infection system. TGG exhibits prominent anti-SARS-CoV activity with a 50% effective concentration of 4.5 μM and a selective index of 240.0. The two-step screening method described here yielded several small molecules that can be used for developing new classes of anti-SARS-CoV drugs and is potentially useful for the high-throughput screening of drugs inhibiting the entry of HIV, hepatitis C virus, and other insidious viruses into their host cells.",,"['Yi, Ling', 'Li, Zhengquan', 'Yuan, Kehu', 'Qu, Xiuxia', 'Chen, Jian', 'Wang, Guangwen', 'Zhang, Hong', 'Luo, Hongpeng', 'Zhu, Lili', 'Jiang, Pengfei', 'Chen, Lirong', 'Shen, Yan', 'Luo, Min', 'Zuo, Guoying', 'Hu, Jianhe', 'Duan, Deliang', 'Nie, Yuchun', 'Shi, Xuanling', 'Wang, Wei', 'Han, Yang', 'Li, Taisheng', 'Liu, Yuqing', 'Ding, Mingxiao', 'Deng, Hongkui', 'Xu, Xiaojie']",,,,
,PMC,cis-Acting RNA Signals in the NS5B C-Terminal Coding Sequence of the Hepatitis C Virus Genome,http://dx.doi.org/10.1128/JVI.78.20.10865-10877.2004,PMC521798,,,"The cis-replicating RNA elements in the 5′ and 3′ nontranslated regions (NTRs) of the hepatitis C virus (HCV) genome have been thoroughly studied before. However, no cis-replicating elements have been identified in the coding sequences of the HCV polyprotein until very recently. The existence of highly conserved and stable stem-loop structures in the RNA polymerase NS5B coding sequence, however, has been previously predicted (A. Tuplin, J. Wood, D. J. Evans, A. H. Patel, and P. Simmonds, RNA 8:824-841, 2002). We have selected for our studies a 249-nt-long RNA segment in the C-terminal NS5B coding region (NS5BCR), which is predicted to form four stable stem-loop structures (SL-IV to SL-VII). By deletion and mutational analyses of the RNA structures, we have determined that two of the stem-loops (SL-V and SL-VI) are essential for replication of the HCV subgenomic replicon in Huh-7 cells. Mutations in the loop and the top of the stem of these RNA elements abolished replicon RNA synthesis but had no effect on translation. In vitro gel shift and filter-binding assays revealed that purified NS5B specifically binds to SL-V. The NS5B-RNA complexes were specifically competed away by unlabeled homologous RNA, to a small extent by 3′ NTR RNA, and only poorly by 5′ NTR RNA. The other two stem-loops (SL-IV and SL-VII) of the NS5BCR domain were found to be important but not essential for colony formation by the subgenomic replicon. The precise function(s) of these cis-acting RNA elements is not known.",,"['Lee, Haekyung', 'Shin, Hyukwoo', 'Wimmer, Eckard', 'Paul, Aniko V.']",,,,
,PMC,"Synthesis and Characterization of a Native, Oligomeric Form of Recombinant Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein",http://dx.doi.org/10.1128/JVI.78.19.10328-10335.2004,PMC516425,,,"We have expressed and characterized the severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein in cDNA-transfected mammalian cells. The full-length spike protein (S) was newly synthesized as an endoglycosidase H (endo H)-sensitive glycoprotein (gp170) that is further modified into an endo H-resistant glycoprotein (gp180) in the Golgi apparatus. No substantial proteolytic cleavage of S was observed, suggesting that S is not processed into head (S1) and stalk (S2) domains as observed for certain other coronaviruses. While the expressed full-length S glycoprotein was exclusively cell associated, a truncation of S by excluding the C-terminal transmembrane and cytoplasmic tail domains resulted in the expression of an endoplasmic reticulum-localized glycoprotein (gp160) as well as a Golgi-specific form (gp170) which was ultimately secreted into the cell culture medium. Chemical cross-linking, thermal denaturation, and size fractionation analyses suggested that the full-length S glycoprotein of SARS-CoV forms a higher order structure of ∼500 kDa, which is consistent with it being an S homotrimer. The latter was also observed in purified virions. The intracellular form of the C-terminally truncated S protein (but not the secreted form) also forms trimers, but with much less efficiency than full-length S. Deglycosylation of the full-length homotrimer with peptide N-glycosidase-F under native conditions abolished recognition of the protein by virus-neutralizing antisera raised against purified virions, suggesting the importance of the carbohydrate in the correct folding of the S protein. These data should aid in the design of recombinant vaccine antigens to prevent the spread of this emerging pathogen.",,"['Song, Hyun Chul', 'Seo, Mi-Young', 'Stadler, Konrad', 'Yoo, Byoung J.', 'Choo, Qui-Lim', 'Coates, Stephen R.', 'Uematsu, Yasushi', 'Harada, Takashi', 'Greer, Catherine E.', 'Polo, John M.', 'Pileri, Piero', 'Eickmann, Markus', 'Rappuoli, Rino', 'Abrignani, Sergio', 'Houghton, Michael', 'Han, Jang H.']",,,,
,PMC,Murine Coronavirus Nonstructural Protein p28 Arrests Cell Cycle in G(0)/G(1) Phase,http://dx.doi.org/10.1128/JVI.78.19.10410-10419.2004,PMC516409,,,"Murine coronavirus mouse hepatitis virus (MHV) gene 1 encodes several nonstructural proteins. The functions are unknown for most of these nonstructural proteins, including p28, which is encoded at the 5′ end of the MHV genome. Transient expression of cloned p28 in several different cultured cells inhibited cell growth, indicating that p28 expression suppressed cell proliferation. Expressed p28 was exclusively localized in the cytoplasm. Cell cycle analysis by flow cytometry demonstrated that p28 expression induced G(0)/G(1) cell cycle arrest. Characterization of various cellular proteins that are involved in regulating cell cycle progression demonstrated that p28 expression resulted in an accumulation of hypophosphorylated retinoblastoma protein (pRb), tumor suppressor p53, and cyclin-dependent kinase (Cdk) inhibitor p21(Cip1). Expression of p28 did not alter the amount of p53 transcripts yet increased the amount of p21(Cip1) transcripts, suggesting that p28 expression increased p53 stability and that p21(Cip1) was transcriptionally activated in a p53-dependent manner. Our present data suggest the following model of p28-induced G(0)/G(1) cell cycle arrest. Expressed cytoplasmic p28 induces the stabilization of p53, and accumulated p53 causes transcriptional upregulation of p21(Cip1). The increased amount of p21(Cip1) suppresses cyclin E/Cdk2 activity, resulting in the inhibition of pRb hyperphosphorylation. Accumulation of hypophosphorylated pRb thus prevents cell cycle progression from G(0)/G(1) to S phase.",,"['Chen, Chun-Jen', 'Sugiyama, Kazuo', 'Kubo, Hideyuki', 'Huang, Cheng', 'Makino, Shinji']",,,,
,PMC,Infectious Entry of West Nile Virus Occurs through a Clathrin-Mediated Endocytic Pathway,http://dx.doi.org/10.1128/JVI.78.19.10543-10555.2004,PMC516396,,,"The pathway of West Nile flavivirus early internalization events was mapped in detail in this study. Overexpression of dominant-negative mutants of Eps15 strongly inhibits West Nile virus (WNV) internalization, and pharmacological drugs that blocks clathrin also caused a marked reduction in virus entry but not caveola-dependent endocytosis inhibitory agent, filipin. Using immunocryoelectron microscopy, WNV particles were seen within clathrin-coated pits after 2 min postinfection. Double-labeling immunofluorescence assays and immunoelectron microscopy performed with anti-WNV envelope or capsid proteins and cellular markers (EEA1 and LAMP1) revealed the trafficking pathway of internalized virus particles from early endosomes to lysosomes and finally the uncoating of the virus particles. Disruption of host cell cytoskeleton (actin filaments and microtubules) with cytochalasin D and nocodazole showed significant reduction in virus infectivity. Actin filaments are shown to be essential during the initial penetration of the virus across the plasma membrane, whereas microtubules are involved in the trafficking of internalized virus from early endosomes to lysosomes for uncoating. Cells treated with lysosomotropic agents were largely resistant to infection, indicating that a low-pH-dependent step is required for WNV infection. In situ hybridization of DNA probes specific for viral RNA demonstrated the trafficking of uncoated viral RNA genomes to the endoplasmic reticulum.",,"['Chu, J. J. H.', 'Ng, M. L.']",,,,
,PMC,Retroviruses Pseudotyped with the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Efficiently Infect Cells Expressing Angiotensin-Converting Enzyme 2,http://dx.doi.org/10.1128/JVI.78.19.10628-10635.2004,PMC516384,,,"Infection of receptor-bearing cells by coronaviruses is mediated by their spike (S) proteins. The coronavirus (SARS-CoV) that causes severe acute respiratory syndrome (SARS) infects cells expressing the receptor angiotensin-converting enzyme 2 (ACE2). Here we show that codon optimization of the SARS-CoV S-protein gene substantially enhanced S-protein expression. We also found that two retroviruses, simian immunodeficiency virus (SIV) and murine leukemia virus, both expressing green fluorescent protein and pseudotyped with SARS-CoV S protein or S-protein variants, efficiently infected HEK293T cells stably expressing ACE2. Infection mediated by an S-protein variant whose cytoplasmic domain had been truncated and altered to include a fragment of the cytoplasmic tail of the human immunodeficiency virus type 1 envelope glycoprotein was, in both cases, substantially more efficient than that mediated by wild-type S protein. Using S-protein-pseudotyped SIV, we found that the enzymatic activity of ACE2 made no contribution to S-protein-mediated infection. Finally, we show that a soluble and catalytically inactive form of ACE2 potently blocked infection by S-protein-pseudotyped retrovirus and by SARS-CoV. These results permit studies of SARS-CoV entry inhibitors without the use of live virus and suggest a candidate therapy for SARS.",,"['Moore, Michael J.', 'Dorfman, Tatyana', 'Li, Wenhui', 'Wong, Swee Kee', 'Li, Yanhan', 'Kuhn, Jens H.', 'Coderre, James', 'Vasilieva, Natalya', 'Han, Zhongchao', 'Greenough, Thomas C.', 'Farzan, Michael', 'Choe, Hyeryun']",,,,
,PMC,Mad cow and other maladies: update on emerging infectious diseases,,PMC1200681,,,,,"Columbus, Cristie",,,,
,PMC,Six month radiological and physiological outcomes in severe acute respiratory syndrome (SARS) survivors,http://dx.doi.org/10.1136/thx.2004.023762,PMC1746851,,,"Background: The long term physiological and radiological outcomes of SARS survivors and their possible determinants are uncertain. Methods: SARS survivors in a follow up clinic in a regional hospital underwent high resolution computed tomography (HRCT) of the thorax and lung function tests 6 months after admission to hospital. The associations between the clinical and demographic data of the patients and the physiological and radiological outcomes were examined. Results: Fifty seven patients took part in the study. Lung function abnormalities were detected in 43 patients (75.4%), with restrictive defects (n = 16) being most common (28.1%). Radiological abnormalities of any degree were detected in 43 patients (75.4%). Only the use of pulse corticosteroids was associated with the presence of CT abnormalities (p = 0.043, OR 6.65, 95% CI 1.06 to 41.73). Conclusions: Physiological and radiological abnormalities are still present in a considerable proportion of SARS survivors at 6 months.",,"['Ng, C', 'Chan, J', 'Kwan, T', 'To, T', 'Chan, Y', 'Ng, F', 'Mok, T']",,,,
,PMC,The SARS coronavirus nucleocapsid protein induces actin reorganization and apoptosis in COS-1 cells in the absence of growth factors,http://dx.doi.org/10.1042/BJ20040984,PMC1134038,,,"In March 2003, a novel coronavirus was isolated from patients exhibiting atypical pneumonia, and was subsequently proven to be the causative agent of the disease now referred to as SARS (severe acute respiratory syndrome). The complete genome of the SARS-CoV (SARS coronavirus) has since been sequenced. The SARS-CoV nucleocapsid (SARS-CoV N) protein shares little homology with other members of the coronavirus family. In the present paper, we show that SARS-CoV N is capable of inducing apoptosis of COS-1 monkey kidney cells in the absence of growth factors by down-regulating ERK (extracellular-signal-regulated kinase), up-regulating JNK (c-Jun N-terminal kinase) and p38 MAPK (mitogen-activated protein kinase) pathways, and affecting their downstream effectors. SARS-CoV N expression also down-regulated phospho-Akt and Bcl-2 levels, and activated caspases 3 and 7. However, apoptosis was independent of the p53 and Fas signalling pathways. Furthermore, activation of the p38 MAPK pathway was found to induce actin reorganization in cells devoid of growth factors. At the cytoskeletal level, SARS-CoV N down-regulated FAK (focal adhesion kinase) activity and also down-regulated fibronectin expression. This is the first report showing the ability of the N protein of SARS-CoV to induce apoptosis and actin reorganization in mammalian cells under stressed conditions.",,"['Surjit, Milan', 'Liu, Boping', 'Jameel, Shahid', 'Chow, Vincent\xa0T.\xa0K.', 'Lal, Sunil\xa0K.']",,,,
,PMC,Colorimetric detection of DNA sequences based on electrostatic interactions with unmodified gold nanoparticles,http://dx.doi.org/10.1073/pnas.0406115101,PMC521116,,,"We find that single- and double-stranded oligonucleotides have different propensities to adsorb on gold nanoparticles in colloidal solution. We use this observation to design a hybridization assay based on color changes associated with gold aggregation. Because the underlying adsorption mechanism is electrostatic, no covalent functionalization of the gold, the probe, or the target DNA is required. Hybridization conditions can be optimized because it is completely separated from the detection step. The assay is complete within 5 min, and <100 femtomoles of target produces color changes observable without instrumentation. Single-base-pair mismatches are easily detected.",,"['Li, Huixiang', 'Rothberg, Lewis']",,,,
,PMC,How to deal with influenza?: Real time surveillance providing information on circulating agents is the key,,PMC517626,,,,,"Jefferson, Tom",,,,
,PMC,Health and social justice,http://dx.doi.org/10.1016/S0140-6736(04)17064-5,PMC4006198,,,,,"Ruger, Jennifer Prah",,,,
,PMC,Predicting genes expressed via −1 and +1 frameshifts,http://dx.doi.org/10.1093/nar/gkh829,PMC519117,,,"Computational identification of ribosomal frameshift sites in genomic sequences is difficult due to their diverse nature, yet it provides useful information for understanding the underlying mechanisms and discovering new genes. We have developed an algorithm that searches entire genomic or mRNA sequences for frameshifting sites, and implements the algorithm as a web-based program called FSFinder (Frameshift Signal Finder). The current version of FSFinder is capable of finding −1 frameshift sites on heptamer sequences X XXY YYZ, and +1 frameshift sites for two genes: protein chain release factor B (prfB) and ornithine decarboxylase antizyme (oaz). We tested FSFinder on ∼190 genomic and partial DNA sequences from a number of organisms and found that it predicted frameshift sites efficiently and with greater sensitivity and specificity than existing approaches. It has improved sensitivity because it considers many known components of a frameshifting cassette and searches these components on both + and − strands, and its specificity is increased because it focuses on overlapping regions of open reading frames and prioritizes candidate frameshift sites. FSFinder is useful for discovering unknown genes that utilize alternative decoding, as well as for analyzing frameshift sites. It is freely accessible at http://wilab.inha.ac.kr/FSFinder/.",,"['Moon, Sanghoon', 'Byun, Yanga', 'Kim, Hong-Jin', 'Jeong, Sunjoo', 'Han, Kyungsook']",,,,
,PMC,Roundtable. Strategies to discourage brain drain.,,PMC2622924,,,"Building health research expertise in developing countries often requires personnel to receive training beyond national borders. For research funding agencies that sponsor this type of training, a major goal is to ensure that trainees return to their country of origin: attaining this objective requires the use of proactive strategies. The strategies described were developed under the extramural acquired immunodeficiency syndrome (AIDS) International Training and Research Program (AITRP) funded by the Fogarty International Center (FIC) at the National Institutes of Health, United States. This programme supports universities in the United States that provide research training to scientists from developing countries to enable them to address the global epidemic of human immunodeficiency virus (HIV)/AIDS and the related tuberculosis (TB) epidemic. This paper describes the strategies employed to discourage brain drain by the principle investigators (PIs) of five of the longest-funded AITRPs (funded for 15 years). Long-term trainees in these programmes spent from 11 to 96 months (an average of 26 months) studying. Using scientific, political and economic strategies that address brain drain issues, PIs working in AITRPs have attained an average rate of return home for their trainees of 80%.",,"['Kupfer, Linda', 'Hofman, Karen', 'Jarawan, Raya', 'McDermott, Jeanne', 'Bridbord, Ken']",,,,
,PMC,Membrane-bound carboxypeptidase E facilitates the entry of eosinophil cationic protein into neuroendocrine cells,http://dx.doi.org/10.1042/BJ20040894,PMC1133959,,,"ECP (eosinophil cationic protein) is a major component of eosinophil granule proteins, and is used as a clinical biomarker for asthma and allergic inflammatory disease. ECP has been implicated in damage to the cell membrane of many tissue types, but the mechanism is not well known. In the present study, mECP–eGFP–6H, a recombinant fusion protein containing mature ECP (mECP), enhanced green fluorescence protein (eGFP) and a His(6) tag (6H), has been expressed, purified and added to GH3 neuroendocrine cells to study the internalization ability of ECP. We found that mECP–eGFP–6H entered into GH3 neuroendocrine cells and inhibited the growth of the cells with an IC(50) of 0.8 μM. By yeast two-hybrid screening and immunoprecipitation, we have identified a specific protein–protein interaction between mECP and CPE (carboxypeptidase E), a well characterized metalloprotease. Further in vivo yeast two-hybrid screening has also revealed that residues 318–387 located in a region of unknown function in mature CPE are indispensable for association with mECP. In addition, the uptake of mECP–eGFP–6H is suppressed by dominant-negative expression of the recycling defect mutant pre-pro-HA–CPE(S471A,E472A) in GH3 cells, suggesting that the entry of mECP–eGFP–6H is associated with the recycling of CPE in GH3 cells. Taken together, we have demonstrated that CPE possesses a novel function to facilitate the entry of ECP to neuroendocrine cells, and such an endocytotic process allows the cytotoxic ECP to inhibit growth of the target cells.",,"['Wu, Chia-Mao', 'Chang, Hao-Teng', 'Chang, Margaret\xa0Dah-Tsyr']",,,,
,PMC,United States prepares for another flu pandemic,,PMC516142,,,,,"Charatan, Fred",,,,
,PMC,To Test Or Not To Test?,,PMC3564298,,,"The use of genetic tests to improve diagnosis and to screen out potential non-responders to costly biologic therapies would seem like a prudent investment, but the practice is far from mainstream. To payers, the issue is more than black and white.",,"SILVERMAN, ED",,,,
,PMC,CORRECTION,http://dx.doi.org/10.1136/bjo.2003.035931.corr1,PMC1772329,,,,,,,,,
,PMC,Eradication versus control: the economics of global infectious disease policies.,,PMC2622975,,,"A disease is controlled if, by means of a public policy, the circulation of an infectious agent is restricted below the level that would be sustained by individuals acting independently to control the disease. A disease is eliminated if it is controlled sufficiently to prevent an epidemic from occurring in a given geographical area. Control and elimination are achieved locally, but a disease can only be eradicated if it is eliminated everywhere. Eradication is plainly a more demanding goal, but it has two advantages over control. First, the economics of eradication can be very favourable when eradication not only reduces infections but also avoids the need for vaccinations in future. Indeed, when eradication is feasible, it will either pay to control it to a fairly low level or to eradicate it. This suggests that, from an economics perspective, diseases that are eliminated in high-income countries are prime candidates for future eradication efforts. Second, the incentives for countries to participate in an eradication initiative can be strong; indeed they can be even stronger than an international control programme. Moreover, high-income countries typically benefit so much that they will be willing to finance elimination in developing countries. Full financing of an eradication effort by nation-states is not always guaranteed, but it can be facilitated by a variety of means. Hence, from the perspective of economics and international relations, eradication has a number of advantages over control. The implications for smallpox and polio eradication programmes are discussed.",,"Barrett, Scott",,,,
,PMC,Senescent BALB/c Mice Are Able To Develop Resistance to Leishmania major Infection,http://dx.doi.org/10.1128/IAI.72.9.5106-5114.2004,PMC517419,,,"Aging has been associated with a decline in immunocompetence and resistance to infections, partially due to dysregulated NO production by macrophages and deficits in mounting Th2 cell responses. We wondered if these alterations would reverse the immune response in experimental leishmaniasis. Bone-marrow-derived macrophages from 2- and 18-month-old (senescent) C57BL/6 or BALB/c mice showed no marked difference in leishmanicidal functions. In vivo infections of resistant C57BL/6 mice with Leishmania major revealed no difference between senescent and young mice. However, among susceptible BALB/c mice, senescent animals showed less foot-pad swelling than young mice, and 40 to 60% of them even showed healing of ulcers, reduced parasite dissemination, and a Th1 cell response. These changes were associated with a spontaneous release of interleukin-12 (IL-12) by macrophages from aged but not from young mice. Since exogenous microbial stimulation can influence immune responses during aging, we also infected senescent mice who were raised under specific-pathogen-free (SPF) conditions. They showed neither resistance nor a Th1 response, but their macrophages still spontaneously released IL-12. A microbiological analysis showed that conventionally kept mice, but not SPF mice, had experienced infection with murine hepatitis virus (MHV), an infection associated with a Th1-like response. We conclude that for the reversal of the immune response, senescence is the premier requirement but needs to be completed by another mandatory event such as microbial stimulation. One of the age-related, but not environment-related, factors is the spontaneous release of IL-12 by macrophages, while confrontation with MHV presents an environment-related difference, with both having the potential to support a Th1 response.",,"['Ehrchen, Jan', 'Sindrilaru, Anca', 'Grabbe, Stephan', 'Schönlau, Frank', 'Schlesiger, Christian', 'Sorg, Clemens', 'Scharffetter-Kochanek, Karin', 'Sunderkötter, Cord']",,,,
,PMC,Dangerous liaisons at the virological synapse,http://dx.doi.org/10.1172/JCI200422812,PMC514595,,,Cell-to-cell viral transmission facilitates the propagation of HIV-1 and human T cell leukemia virus type 1. Mechanisms of cell-to-cell transmission by retroviruses were not well understood until the recent description of virological synapses (VSs). VSs function as specialized sites of immune cell-to-cell contact that direct virus infection. Deciphering the molecular mechanisms of VS formation provides a fascinating insight into how pathogens subvert immune cell communication programs and achieve viral spread.,,"['Piguet, Vincent', 'Sattentau, Quentin']",,,,
,PMC,SARS coronavirus in tears,,PMC1770424,,,,,,,,,
,PMC,Is the inverse care law no longer operating?,,PMC1732897,,,,,"['Adams, J.', 'White, M.']",,,,
,PMC,Epidemiology of SARS: the missing pathogen?,http://dx.doi.org/10.1136/jech.2003.015040,PMC1732895,,,,,"Frizzell, R.",,,,
,PMC,Do socioeconomic conditions reflect a high exposure to air pollution or more sensitive health conditions?,,PMC1732873,,,,,"['Filleul, L.', 'Harrabi, I.', 'Braga, A.', 'Martins, M. C.', 'Pereira, L. A.', 'Martins, M.']",,,,
,PMC,Ceacam1a(−/−) Mice Are Completely Resistant to Infection by Murine Coronavirus Mouse Hepatitis Virus A59,http://dx.doi.org/10.1128/JVI.78.18.10156-10165.2004,PMC515023,,,"CEACAM1a glycoproteins are members of the immunoglobulin (Ig) superfamily and the carcinoembryonic antigen family. Isoforms expressing either two or four alternatively spliced Ig-like domains in mice have been found in a number of epithelial, endothelial, or hematopoietic tissues. CEACAM1a functions as an intercellular adhesion molecule, an angiogenic factor, and a tumor cell growth inhibitor. Moreover, the mouse and human CEACAM1a proteins are targets of viral or bacterial pathogens, respectively, including the murine coronavirus mouse hepatitis virus (MHV), Haemophilus influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis, as well as Moraxella catarrhalis in humans. We have shown that targeted disruption of the Ceacam1a (MHVR) gene resulting in a partial ablation of the protein in mice (p/p mice) led to reduced susceptibility to MHV-A59 infection of the modified mice in the BALB/c background. We have now engineered and produced a Ceacam1a(−/−) mouse that exhibits complete ablation of the CEACAM1a protein in every tissue where it is normally expressed. We report that 3-week-old Ceacam1a(−/−) mice in the C57BL/6 genetic background are fully resistant to MHV-A59 infection by both intranasal and intracerebral routes. Whereas virus-inoculated wild-type +/+ C57BL/6 mice showed profound liver damage and spinal cord demyelination under these conditions, Ceacam1a(−/−) mice displayed normal livers and spinal cords. Virus was recovered from liver and spinal cord tissues of +/+ mice but not of −/− mice. These results indicate that CEACAM1a is the sole receptor for MHV-A59 in both liver and brain and that its deletion from the mouse renders the mouse completely resistant to infection by this virus.",,"['Hemmila, Erin', 'Turbide, Claire', 'Olson, Melanie', 'Jothy, Serge', 'Holmes, Kathryn V.', 'Beauchemin, Nicole']",,,,
,PMC,Cytoplasmic Dynein Mediates Adenovirus Binding to Microtubules,http://dx.doi.org/10.1128/JVI.78.18.10122-10132.2004,PMC515014,,,"During infection, adenovirus (Ad) capsids undergo microtubule-dependent retrograde transport as part of a program of vectorial transport of the viral genome to the nucleus. The microtubule-associated molecular motor, cytoplasmic dynein, has been implicated in the retrograde movement of Ad. We hypothesized that cytoplasmic dynein constituted the primary mode of association of Ad with microtubules. To evaluate this hypothesis, an Ad-microtubule binding assay was established in which microtubules were polymerized with taxol, combined with Ad in the presence or absence of microtubule-associated proteins (MAPs), and centrifuged through a glycerol cushion. The addition of purified bovine brain MAPs increased the fraction of Ad in the microtubule pellet from 17.3% ± 3.5% to 80.7% ± 3.8% (P < 0.01). In the absence of tubulin polymerization or in the presence of high salt, no Ad was found in the pellet. Ad binding to microtubules was not enhanced by bovine brain MAPs enriched for tau protein or by the addition of bovine serum albumin. Enhanced Ad-microtubule binding was also observed by using a fraction of MAPs purified from lung A549 epithelial cell lysate which contained cytoplasmic dynein. Ad-microtubule interaction was sensitive to the addition of ATP, a hallmark of cytoplasmic dynein-dependent microtubule interactions. Immunodepletion of cytoplasmic dynein from the A549 cell lysate abolished the MAP-enhanced Ad-microtubule binding. The interaction of Ad with both dynein and dynactin complexes was demonstrated by coimmunoprecipitation. Partially uncoated capsids isolated from cells 40 min after infection also exhibited microtubule binding. In summary, the primary mode of Ad attachment to microtubules occurs though cytoplasmic dynein-mediated binding.",,"['Kelkar, Samir A.', 'Pfister, K. Kevin', 'Crystal, Ronald G.', 'Leopold, Philip L.']",,,,
,PMC,Genetic Analysis of Determinants for Spike Glycoprotein Assembly into Murine Coronavirus Virions: Distinct Roles for Charge-Rich and Cysteine-Rich Regions of the Endodomain,http://dx.doi.org/10.1128/JVI.78.18.9904-9917.2004,PMC514984,,,"The coronavirus spike protein (S) forms the distinctive virion surface structures that are characteristic of this viral family, appearing in negatively stained electron microscopy as stems capped with spherical bulbs. These structures are essential for the initiation of infection through attachment of the virus to cellular receptors followed by fusion to host cell membranes. The S protein can also mediate the formation of syncytia in infected cells. The S protein is a type I transmembrane protein that is very large compared to other viral fusion proteins, and all except a short carboxy-terminal segment of the S molecule constitutes the ectodomain. For the prototype coronavirus mouse hepatitis virus (MHV), it has previously been established that S protein assembly into virions is specified by the carboxy-terminal segment, which comprises the transmembrane domain and the endodomain. We have genetically dissected these domains in the MHV S protein to localize the determinants of S incorporation into virions. Our results establish that assembly competence maps to the endodomain of S, which was shown to be sufficient to target a heterologous integral membrane protein for incorporation into MHV virions. In particular, mutational analysis indicated a major role for the charge-rich carboxy-terminal region of the endodomain. Additionally, we found that the adjacent cysteine-rich region of the endodomain is critical for fusion of infected cells, confirming results previously obtained with S protein expression systems.",,"['Ye, Rong', 'Montalto-Morrison, Cynthia', 'Masters, Paul S.']",,,,
,PMC,Identification and Characterization of Severe Acute Respiratory Syndrome Coronavirus Replicase Proteins,http://dx.doi.org/10.1128/JVI.78.18.9977-9986.2004,PMC514967,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) encodes proteins required for RNA transcription and genome replication as large polyproteins that are proteolytically processed by virus-encoded proteinases to produce mature replicase proteins. In this report, we generated antibodies against SARS-CoV predicted replicase protein and used the antibodies to identify and characterize 12 of the 16 predicted mature replicase proteins (nsp1, nsp2, nsp3, nsp4, nsp5, nsp8, nsp9, nsp12, nsp13, nsp14, nsp15, and nsp16) in SARS-CoV-infected Vero cells. Immunoblot analysis of infected-cell lysates identified proteins of the predicted sizes. Immunofluorescence microscopy detected similar patterns of punctate perinuclear and distributed cytoplasmic foci with all replicase antibodies and as early as 6 h postinfection. Dual-labeling studies demonstrated colocalization of replicase protein nsp8 with nsp2 and nsp3 in cytoplasmic complexes and also with LC3, a protein marker for autophagic vacuoles. Antibodies directed against mouse hepatitis virus (MHV) virions and against the putative RNA-dependent RNA polymerase (Pol) detected SARS-CoV nucleocapsid and nsp12 (Pol), respectively, in SARS-CoV-infected Vero cells. These results confirm the predicted protein processing pattern for mature SARS-CoV replicase proteins, demonstrate localization of replicase proteins to cytoplasmic complexes containing markers for autophagosome membranes, and suggest conservation of protein epitopes in the replicase and nucleocapsid of SARS-CoV and the group II coronavirus, MHV. Further, the results demonstrate the ability of replicase antibodies to detect SARS-CoV-infected cells as early as 6 h postinfection and thus represent important tools for studies of SARS-CoV replication, inhibition, and diagnosis.",,"['Prentice, Erik', 'McAuliffe, Josephine', 'Lu, Xiaotao', 'Subbarao, Kanta', 'Denison, Mark R.']",,,,
,PMC,Retroviral Vectors Pseudotyped with Severe Acute Respiratory Syndrome Coronavirus S Protein,http://dx.doi.org/10.1128/JVI.78.17.9007-9015.2004,PMC506966,,,"The worldwide outbreak of severe acute respiratory syndrome (SARS) was shown to be associated with a novel coronavirus (CoV) now called SARS CoV. We report here the generation of SARS CoV S protein-pseudotyped murine leukemia virus (MLV) vector particles. The wild-type S protein pseudotyped MLV vectors, although at a low efficiency. Partial deletion of the cytoplasmic tail of S dramatically increased infectivity of pseudotypes, with titers only two- to threefold lower than those of pseudotypes generated in parallel with the vesicular stomatitis virus G protein. S-pseudotyped MLV particles were used to analyze viral tropism. MLV(SARS) pseudotypes and wild-type SARS CoV displayed similar cell types and tissue and host restrictions, indicating that the expression of a functional receptor is the major restraint in permissiveness to SARS CoV infection. Efficient gene transfer could be detected in Vero and CaCo2 cells, whereas the level of gene marking of 293T, HeLa, and HepG2 cells was only slightly above background levels. A cat cell line and a dog cell line were not susceptible. Interestingly, PK-15, a porcine kidney cell line, and primary porcine kidney cells were also highly permissive for SARS S pseudotypes and wild-type SARS CoV. This finding suggests that swine may be susceptible to SARS infection and may be a source for infection of humans. Taken together, these results indicate that MLV(SARS) pseudotypes are highly valuable for functional studies of viral tropism and entry and, in addition, can be a powerful tool for the development of therapeutic entry inhibitors without posing a biohazard to human beings.",,"['Giroglou, Tsanan', 'Cinatl, Jindrich', 'Rabenau, Holger', 'Drosten, Christian', 'Schwalbe, Harald', 'Doerr, Hans Wilhelm', 'von Laer, Dorothee']",,,,
,PMC,The N-Terminal Region of the Murine Coronavirus Spike Glycoprotein Is Associated with the Extended Host Range of Viruses from Persistently Infected Murine Cells,http://dx.doi.org/10.1128/JVI.78.17.9073-9083.2004,PMC506962,,,"Although murine coronaviruses naturally infect only mice, several virus variants derived from persistently infected murine cell cultures have an extended host range. The mouse hepatitis virus (MHV) variant MHV/BHK can infect hamster, rat, cat, dog, monkey, and human cell lines but not the swine testis (ST) porcine cell line (J. H. Schickli, B. D. Zelus, D. E. Wentworth, S. G. Sawicki, and K. V. Holmes, J. Virol. 71:9499-9507, 1997). The spike (S) gene of MHV/BHK had 63 point mutations and a 21-bp insert that encoded 56 amino acid substitutions and a 7-amino-acid insert compared to the parental MHV strain A59. Recombinant viruses between MHV-A59 and MHV/BHK were selected in hamster cells. All of the recombinants retained 21 amino acid substitutions and a 7-amino-acid insert found in the N-terminal region of S of MHV/BHK, suggesting that these residues were responsible for the extended host range of MHV/BHK. Flow cytometry showed that MHV-A59 bound only to cells that expressed the murine glycoprotein receptor CEACAM1a. In contrast, MHV/BHK and a recombinant virus, k6c, with the 21 amino acid substitutions and 7-amino-acid insert in S bound to hamster (BHK) and ST cells as well as murine cells. Thus, 21 amino acid substitutions and a 7-amino-acid insert in the N-terminal region of the S glycoprotein of MHV/BHK confer the ability to bind and in some cases infect cells of nonmurine species.",,"['Schickli, Jeanne H.', 'Thackray, Larissa B.', 'Sawicki, Stanley G.', 'Holmes, Kathryn V.']",,,,
,PMC,Influenza: Emergence and Control,http://dx.doi.org/10.1128/JVI.78.17.8951-8959.2004,PMC506949,,,,,"['Lipatov, Aleksandr S.', 'Govorkova, Elena A.', 'Webby, Richard J.', 'Ozaki, Hiroichi', 'Peiris, Malik', 'Guan, Yi', 'Poon, Leo', 'Webster, Robert G.']",,,,
,PMC,Emotional and Behavioral Consequences of Bioterrorism: Planning a Public Health Response,http://dx.doi.org/10.1111/j.0887-378X.2004.00317.x,PMC2690224,,,Millions of dollars have been spent improving the public health system's bioterrorism response capabilities. Yet relatively little attention has been paid to precisely how the public will respond to bioterrorism and how emotional and behavioral responses might complicate an otherwise successful response. This article synthesizes the available evidence about the likely emotional and behavioral consequences of bioterrorism to suggest what decision makers can do now to improve that response. It examines the emotional and behavioral impact of previous “bioterrorism-like” events and summarizes interviews with experts who have responded to such events or conducted research on the effects of communitywide disasters. The article concludes by reflecting on the evidence and experts’ perspectives to suggest actions to be taken now and future policy and research priorities.,,"['Stein, Bradley D', 'Tanielian, Terri L', 'Eisenman, David P', 'Keyser, Donna J', 'Burnam, M Audrey', 'Pincus, Harold A']",,,,
,PMC,Chronic obstructive pulmonary disease: the clinical management of an acute exacerbation,http://dx.doi.org/10.1136/pgmj.2004.019182,PMC1743105,,,"Exacerbations of chronic obstructive pulmonary disease impose a considerable burden of morbidity, mortality, and health care cost. Management guidelines outlining best practice, based largely on consensus expert opinion, were produced by a number of organisations during the last decade. Current interest in the field is high. This has resulted in the publication of many further studies which have extended our understanding of the pathology involved and provided, for the first time, an evidence base for many of the therapeutic options. In this review we aim to bring the non-specialist reader up to date with current management principles and the evidence underlying such interventions.",,"['Hurst, J', 'Wedzicha, J']",,,,
,PMC,Contacting passengers after exposure to measles on an international flight: Implications for responding to new disease threats and bioterrorism.,http://dx.doi.org/10.1016/j.phr.2004.07.002,PMC1497663,,,"On May 21, 2000, a passenger with measles traveled from Japan to Hawai'i on a seven-hour flight. When the flight landed, the U.S. Public Health Service (USPHS) Quarantine Station in Honolulu alerted passengers that a suspected case of measles had been identified, but they were not detained. The next day, to offer appropriate post-exposure prophylaxis, the Hawai'i Department of Health (HDOH) attempted to contact all passengers from the flight using information from the airline, U.S. Customs declaration forms, and tour agencies. Of 335 total passengers, 270 (81%) were successfully reached and provided complete information. The mean time from exposure to contact for all respondents was 61 hours (95% confidence interval 57, 66). A total of 202 (75%) of the responding passengers were contacted within 72 hours after exposure, the time period during which administration of measles vaccine would have provided protection for susceptible individuals. The time-to-contact was significantly longer for passengers who did not stay in hotels than for hotel guests. Customs forms proved to be of limited utility in contacting international travelers. This experience highlights the need for more complete and timely methods of contacting passengers potentially exposed to infectious agents aboard flights.",,"['Lasher, Lara E.', 'Ayers, Tracy L.', 'Amornkul, Pauli N.', 'Nakatab, Michele N.', 'Effler, Paul V.']",,,,
,PMC,How outbreaks of infectious disease are detected: a review of surveillance systems and outbreaks.,http://dx.doi.org/10.1016/j.phr.2004.07.003,PMC1497658,,,"To learn how outbreaks of infectious disease are detected and to describe the entities and information systems that together function to identify outbreaks in the U.S., the authors drew on multiple sources of information to create a description of existing surveillance systems and how they interact to detect outbreaks. The results of this analysis were summarized in a system diagram. The authors reviewed a sample of recent outbreaks to determine how they were detected, with reference to the system diagram. The de facto U.S. system for detection of outbreaks consists of five components: the clinical health care system, local/state health agencies, federal agencies, academic/professional organizations, and collaborating governmental organizations. Primary data collection occurs at the level of clinical health care systems and local health agencies. The review of a convenience sample of outbreaks showed that all five components of the system participated in aggregating, analyzing, and sharing data. The authors conclude that the current U.S. approach to detection of disease outbreaks is complex and involves many organizations interacting in a loosely coupled manner. State and local health departments and the health care system are major components in the detection of outbreaks.",,"['Dato, Virginia', 'Wagner, Michael M.', 'Fapohunda, Abi']",,,,
,PMC,Multiplexed Genetic Analysis Using an Expanded Genetic Alphabet,http://dx.doi.org/10.1373/clinchem.2004.034330,PMC1592527,,,"BACKGROUND: All states require some kind of testing for newborns, but the policies are far from standardized. In some states, newborn screening may include genetic tests for a wide range of targets, but the costs and complexities of the newer genetic tests inhibit expansion of newborn screening. We describe the development and technical evaluation of a multiplex platform that may foster increased newborn genetic screening. METHODS: MultiCode(®) PLx involves three major steps: PCR, target-specific extension, and liquid chip decoding. Each step is performed in the same reaction vessel, and the test is completed in ~3 h. For site-specific labeling and room-temperature decoding, we use an additional base pair constructed from isoguanosine and isocytidine. We used the method to test for mutations within the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The developed test was performed manually and by automated liquid handling. Initially, 225 samples with a range of genotypes were tested retrospectively with the method. A prospective study used samples from >400 newborns. RESULTS: In the retrospective study, 99.1% of samples were correctly genotyped with no incorrect calls made. In the perspective study, 95% of the samples were correctly genotyped for all targets, and there were no incorrect calls. CONCLUSIONS: The unique genetic multiplexing platform was successfully able to test for 31 targets within the CFTR gene and provides accurate genotype assignments in a clinical setting.",,"['Johnson, Scott C.', 'Marshall, David J.', 'Harms, Gerda', 'Miller, Christie M.', 'Sherrill, Christopher B.', 'Beaty, Edward L.', 'Lederer, Scott A.', 'Roesch, Eric B.', 'Madsen, Gary', 'Hoffman, Gary L.', 'Laessig, Ronald H.', 'Kopish, Greg J.', 'Baker, Mei Wang', 'Benner, Steven A.', 'Farrell, Philip M.', 'Prudent, James R.']",,,,
,PMC,VITAMIN E AND RESPIRATORY INFECTIONS AMONG ELDERLY NURSING HOME RESIDENTS: A RANDOMIZED CONTROLLED TRIAL,http://dx.doi.org/10.1001/jama.292.7.828,PMC2377357,,,"CONTEXT: Respiratory infections are prevalent in the elderly, resulting in increased morbidity, mortality, and utilization of health care services. Vitamin E supplementation has been shown to improve immune response in the elderly. However, the clinical importance of these findings has not been determined. OBJECTIVE: To investigate the effect of 1-year vitamin E supplementation on respiratory infections in elderly nursing home residents DESIGN: A randomized, double-blind, placebo-controlled trial conducted from April 1998 to August 2001 SETTING: 33 long-term care facilities in the Boston, Massachusetts area PARTICIPANTS: 617 subjects ≥65 years old, who met the study’s eligibility criteria were enrolled, 73% of whom completed the study. The follow-up time (mean ± SD) was 317±104 and 321±97 days, E and placebo respectively, for all subjects enrolled in the study. INTERVENTION: A daily vitamin E (200 IU) or placebo capsule; all subjects received a capsule containing 1/2 the Recommended Daily Allowance of essential vitamins and minerals. MAIN OUTCOME MEASURES: Incidence, number of subjects and number of days with respiratory infections (upper and lower), and number of new antibiotic prescriptions. RESULTS: There was no statistically significant effect of vitamin E on incidence or number of days with infection for all, upper, or lower respiratory infections. However, fewer vitamin E-supplemented subjects acquired one or more respiratory infections (65% vs 74%, risk ratio=0.88, 95% CI=0.75–0.99, p=0.036 for completed subjects; 60% vs 68%, risk ratio=0.88, 95% CI=0.76–1.00, p=0.048 for all subjects), or upper respiratory infections (50% vs 62%, risk ratio = 0.81, 95% CI=0.66–0.96, p=0.013 for completed subjects; 44% vs 52%, risk ratio=0.84, 95% CI=0.69–1.00, p=0.051 for all subjects). Post hoc sub-group analysis on common colds indicated that the vitamin E group had a lower incidence of common cold (0.66 vs 0.83 per subject-year, rate ratio=0.80, 95% CI=0.64–0.98, p=0.035 for completed subjects; 0.67 vs 0.81 per subject-year, rate ratio=0.83, 95% CI=0.68–1.01, p=0.057 for all subjects) and fewer subjects in the vitamin E group acquired one or more colds (46% vs 57%, risk ratio=0.80, 95% CI=0.64–0.96, p=0.016 for completed subjects; 40% vs 48%, risk ratio=0.83, 95% CI=0.67–1.00, p=0.052 for all subjects). There was no statistically significant vitamin E effect on antibiotic use. CONCLUSIONS: Supplementation with 200 IU per day vitamin E did not have a statistically significant effect on lower respiratory infections in elderly nursing home residents. However, we observed a protective effect of vitamin E supplementation on upper respiratory infections, particularly the common cold, that merits further investigation.",,"['Meydani, Simin Nikbin', 'Leka, Lynette S.', 'Fine, Basil C.', 'Dallal, Gerard E.', 'Keusch, Gerald T.', 'Singh, Maria Fiatarone', 'Hamer, Davidson H.']",,,,
,PMC,SARS vaccine undergoing animal testing,http://dx.doi.org/10.1503/cmaj.1041149,PMC509036,,,,,"Tamburri, Rosanna",,,,
,PMC,Interfacing between primary and secondary care is needed,,PMC509389,,,,,"['Lee, Albert', 'Wong, William', 'Wong, Samuel Yeung Shan', 'Tsang, Kwong Ka']",,,,
,PMC,In brief,,PMC509335,,,,,,,,,
,PMC,Major genetic marker of nidoviruses encodes a replicative endoribonuclease,http://dx.doi.org/10.1073/pnas.0403127101,PMC514660,,,"Coronaviruses are important pathogens that cause acute respiratory diseases in humans. Replication of the ≈30-kb positive-strand RNA genome of coronaviruses and discontinuous synthesis of an extensive set of subgenome-length RNAs (transcription) are mediated by the replicase-transcriptase, a barely characterized protein complex that comprises several cellular proteins and up to 16 viral subunits. The coronavirus replicase-transcriptase was recently predicted to contain RNA-processing enzymes that are extremely rare or absent in other RNA viruses. Here, we established and characterized the activity of one of these enzymes, replicative nidoviral uridylate-specific endoribonuclease (NendoU). It is considered a major genetic marker that discriminates nidoviruses (Coronaviridae, Arteriviridae, and Roniviridae) from all other RNA virus families. Bacterially expressed forms of NendoU of severe acute respiratory syndrome coronavirus and human coronavirus 229E were revealed to cleave single-stranded and double-stranded RNA in a Mn(2+)-dependent manner. Single-stranded RNA was cleaved less specifically and effectively, suggesting that double-stranded RNA is the biologically relevant NendoU substrate. Double-stranded RNA substrates were cleaved upstream and downstream of uridylates at GUU or GU sequences to produce molecules with 2′-3′ cyclic phosphate ends. 2′-O-ribose-methylated RNA substrates proved to be resistant to cleavage by NendoU, indicating a functional link with the 2′-O-ribose methyltransferase located adjacent to NendoU in the coronavirus replicative polyprotein. A mutagenesis study verified potential active-site residues and allowed us to inactivate NendoU in the full-length human coronavirus 229E clone. Substitution of D6408 by Ala was shown to abolish viral RNA synthesis, demonstrating that NendoU has critical functions in viral replication and transcription.",,"['Ivanov, Konstantin A.', 'Hertzig, Tobias', 'Rozanov, Mikhail', 'Bayer, Sonja', 'Thiel, Volker', 'Gorbalenya, Alexander E.', 'Ziebuhr, John']",,,,
,PMC,Inhibition of Hepatitis C Virus Replication by Arsenic Trioxide,http://dx.doi.org/10.1128/AAC.48.8.2876-2882.2004,PMC478516,,,"Hepatitis C virus (HCV) is a serious global problem, and present therapeutics are inadequate to cure HCV infection. In the present study, various antiviral assays show that As(2)O(3) at submicromolar concentrations is capable of inhibiting HCV replication. The 50% effective concentration (EC(50)) of As(2)O(3) required to inhibit HCV replication was 0.35 μM when it was determined by a reporter-based HCV replication assay, and the EC(50) was below 0.2 μM when it was determined by quantitative reverse transcription-PCR analysis. As(2)O(3) did not cause cellular toxicity at this concentration, as revealed by an MTS [3-(4,5-dimethylthiozol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay. A combination of As(2)O(3) and alpha interferon exerted synergistic effects against HCV, as revealed by a multiple linear logistic model and isobologram analysis. Furthermore, in an alternative HCV antiviral system that may recapitulate additional steps involved in HCV infection and replication, As(2)O(3) at 0.3 μM totally abolished the HCV signal, whereas alpha interferon at a high dose (5,000 IU/ml) only partially suppressed the HCV signal. The study highlights the indications for use of a novel class of anti-HCV agent. Further elucidation of the exact antiviral mechanism of As(2)O(3) may lead to the development of agents with potent activities against HCV or related viruses.",,"['Hwang, Der-Ren', 'Tsai, Yuan-Chin', 'Lee, Jin-Ching', 'Huang, Kuo-Kuei', 'Lin, Ren-Kuo', 'Ho, Chia-Hua', 'Chiou, Jeng-Min', 'Lin, Ying-Ting', 'Hsu, John T. A.', 'Yeh, Chau-Ting']",,,,
,PMC,Hypoxaemia in sickle cell disease,,PMC1720037,,,,,,,,,
,PMC,Mandatory temperature monitoring in schools during SARS,http://dx.doi.org/10.1136/adc.2003.047084,PMC1720033,,,,,"['Chng, S', 'Chia, F', 'Leong, K', 'Kwang, Y', 'Ma, S', 'Lee, B', 'Vaithinathan, R', 'Tan, C']",,,,
,PMC,A randomised trial comparing 0.02% mitomycin C and limbal conjunctival autograft after excision of primary pterygium,http://dx.doi.org/10.1136/bjo.2003.036830,PMC1772290,,,"Background: Mitomycin C (MMC) and limbal conjunctival autograft (LCAU) are two known useful adjuvants in the prevention of pterygial recurrence. This study was conducted to compare the outcome of these two treatments. Methods: Prospective study on consecutive cases of primary pterygium (February 2001 to March 2002) randomised into two adjuvant groups: (1) intraoperative 0.02% MMC for 5 minutes or (2) LCAU. Patients were followed for recurrence (defined as fibrovascular tissue invading the cornea >1.5mm) and complications for a period of one year. Results: 115 eyes in 114 patients who completed the study were randomised to receive MMC (n = 63) and LCAU (n = 52). There were 10 recurrences (15.9%) in the MMC group and only one recurrence (1.9%) in the LCAU group. There was a statistically significant difference in the recurrence rate between the two groups (p = 0.04). There were a total of three conjunctival cysts, three symblephara, one granuloma, and one dellen. No other visually significant complications were encountered in either group. Conclusion: Although LCAU resulted in better one year success rates, it is technically more difficult and inapplicable in cases with previous limbal disturbance. Simple excision followed by MMC or LCAU are both safe and acceptable adjuvants for pterygium excision. Choice of adjuvant should be carefully made based on assessment of recurrence risk, local practices, and surgeon’s expertise.",,"['Young, A L', 'Leung, G Y S', 'Wong, A K K', 'Cheng, L L', 'Lam, D S C']",,,,
,PMC,Estimating SARS Incubation Period,http://dx.doi.org/10.3201/eid1008.040284,PMC3320416,15503397,NO-CC CODE,,2004 Aug,"['Wong, Tze-wai', 'Tam, Wilson']",Emerg Infect Dis,,,
,PMC,SARS Outbreak in Taiwan,http://dx.doi.org/10.3201/eid1008.040115,PMC3320396,15503404,NO-CC CODE,,2004 Aug,"['Hsueh, Po-Ren', 'Yang, Pan-Chyr']",Emerg Infect Dis,,,
,PMC,SARS preventive and risk behaviours of Hong Kong air travellers.,,PMC2870154,,,"This study aims to investigate Severe Acute Respiratory Syndrome (SARS)-related behaviours of travellers returning to Hong Kong by air. A total of 820 travellers returning to Hong Kong by air were interviewed about their SARS-related behaviours in April 2003. Three quarters of the respondents wore a mask most/all of the time on board, 15% did so in public places at the travel destination. Perceived susceptibility to SARS at the destination predicted mask-wearing in public places and avoidance of crowded places, and perceived efficacy was a predictor for mask-wearing during flight. Approximately 16% of the respondents stated that they would delay their medical consultation for flu-like symptoms until returning to Hong Kong. Nearly 18.2% stated that they would not wear a mask in public places at the destination if they had flu-like symptoms. Education programmes, special services and effective thermal screening are required to minimize the chance of the spread of SARS by air travellers.",,"['Lau, Joseph T. F.', 'Yang, Xilin', 'Tsui, Hiyi', 'Pang, Ellie', 'Kim, Jean H.']",,,,
,PMC,Analysis of Serum Cytokines in Patients with Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1128/IAI.72.8.4410-4415.2004,PMC470699,,,"Severe acute respiratory syndrome (SARS) is an acute infectious disease of the respiratory system. Although a novel coronavirus has been identified as the causative agent of SARS, the pathogenic mechanisms of SARS are not understood. In this study, sera were collected from healthy donors, patients with SARS, patients with severe SARS, and patients with SARS in convalescence. The serum concentrations of interleukin-1 (IL-1), IL-4, IL-6, IL-8, IL-10, tumor growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) were measured by enzyme-linked immunosorbent assays (ELISA). The concentrations of IL-1 and TNF-α were not significantly different in different groups. The IL-6 concentration was increased in SARS patients and was significantly elevated in severe SARS patients, but the IL-6 concentrations were similar in convalescent patients and control subjects, suggesting that there was a positive relationship between the serum IL-6 concentration and SARS severity. The concentrations of IL-8 and TGF-β were decreased in SARS patients and significantly reduced in severe SARS patients, but they were comparable in convalescent SARS patients and control subjects, suggesting that there was a negative relationship between the IL-8 and TGF-β concentrations and SARS severity. The concentrations of IFN-γ, IL-4, and IL-10 showed significant changes only in convalescent SARS patients. The IFN-γ and IL-4 levels were decreased, while the levels of IL-10 were increased, and the differences between convalescent SARS patients and other patient groups were statistically significant. These results suggest that there are different immunoregulatory events during and after SARS and may contribute to our understanding of the pathogenesis of this syndrome.",,"['Zhang, Yuanchun', 'Li, Jing', 'Zhan, Yuliang', 'Wu, Lianqiu', 'Yu, Xueying', 'Zhang, Wenjian', 'Ye, Liya', 'Xu, Shiqing', 'Sun, Ruihua', 'Wang, Yunting', 'Lou, Jinning']",,,,
,PMC,Comparison of the Directigen Flu A+B Membrane Enzyme Immunoassay with Viral Culture for Rapid Detection of Influenza A and B Viruses in Respiratory Specimens,http://dx.doi.org/10.1128/JCM.42.8.3707-3710.2004,PMC497654,,,"The performance of a commercially available, rapid membrane enzyme immunoassay for influenza A and B virus detection was compared to that of viral culture in 4,092 respiratory specimens collected from patients presenting with respiratory symptoms during the 2002-2003 influenza season. The test's overall sensitivity was 43.83%, lower than previously reported but similar for detection of both influenza A and B viruses (42.98 versus 44.76%). However, specificity, 99.74%, was excellent for both influenza A and B viruses (99.82 versus 99.92%). These values make this test a very good confirmatory test when clinical suspicion is high, but a less accurate screening test for large populations.",,"['Cazacu, Andreea C.', 'Chung, Sooyoung E.', 'Greer, Jewel', 'Demmler, Gail J.']",,,,
,PMC,Comparison of a New Lateral-Flow Chromatographic Membrane Immunoassay to Viral Culture for Rapid Detection and Differentiation of Influenza A and B Viruses in Respiratory Specimens,http://dx.doi.org/10.1128/JCM.42.8.3661-3664.2004,PMC497609,,,"The performance of a new rapid lateral-flow chromatographic membrane immunoassay test kit for detection of influenza virus was evaluated and compared to that of viral culture in respiratory secretions collected from 400 adults and children seen at three large university hospitals during the recent 2003 influenza season. The rapid test provided results in 15 min, with excellent overall performance statistics (sensitivity, 94.4%; specificity, 100%; positive predictive value, 100%; negative predictive value, 97.5%). Both influenza A and B type viruses were reliably detected, with no significant difference in performance statistics noted by influenza virus type or by the center performing the test.",,"['Cazacu, Andreea C.', 'Demmler, Gail J.', 'Neuman, Mark A.', 'Forbes, Betty A.', 'Chung, Sooyoung', 'Greer, Jewel', 'Alvarez, Ana E.', 'Williams, Robin', 'Bartholoma, Nadine Y.']",,,,
,PMC,Scale of levels of care versus DNR orders,http://dx.doi.org/10.1136/jme.2003.002436,PMC1733901,,,,,"['Vanpee, D', 'Swine, C']",,,,
,PMC,Human Coronavirus 229E Binds to CD13 in Rafts and Enters the Cell through Caveolae,http://dx.doi.org/10.1128/JVI.78.16.8701-8708.2004,PMC479086,,,"CD13, a receptor for human coronavirus 229E (HCoV-229E), was identified as a major component of the Triton X-100-resistant membrane microdomain in human fibroblasts. The incubation of living fibroblasts with an anti-CD13 antibody on ice gave punctate labeling that was evenly distributed on the cell surface, but raising the temperature to 37°C before fixation caused aggregation of the labeling. The aggregated labeling of CD13 colocalized with caveolin-1 in most cells. The HCoV-229E virus particle showed a binding and redistribution pattern that was similar to that caused by the anti-CD13 antibody: the virus bound to the cell evenly when incubated on ice but became colocalized with caveolin-1 at 37°C; importantly, the virus also caused sequestration of CD13 to the caveolin-1-positive area. Electron microscopy confirmed that HCoV-229E was localized near or at the orifice of caveolae after incubation at 37°C. The depletion of plasmalemmal cholesterol with methyl β-cyclodextrin significantly reduced the HCoV-229E redistribution and subsequent infection. A caveolin-1 knockdown by RNA interference also reduced the HCoV-229E infection considerably. The results indicate that HCoV-229E first binds to CD13 in the Triton X-100-resistant microdomain, then clusters CD13 by cross-linking, and thereby reaches the caveolar region before entering cells.",,"['Nomura, Ryuji', 'Kiyota, Asuka', 'Suzaki, Etsuko', 'Kataoka, Katsuko', 'Ohe, Yoshihide', 'Miyamoto, Kaoru', 'Senda, Takao', 'Fujimoto, Toyoshi']",,,,
,PMC,Development of a DNA Vaccine Targeting Human Papillomavirus Type 16 Oncoprotein E6,http://dx.doi.org/10.1128/JVI.78.16.8468-8476.2004,PMC479075,,,"Human papillomavirus (HPV), particularly type 16 (HPV-16), is present in more than 99% of cervical cancers. The HPV oncoproteins E6 and E7 are constantly expressed and therefore represent ideal targets for HPV vaccine development. We previously developed DNA vaccines encoding calreticulin (CRT) linked to HPV-16 E7 and generated potent E7-specific CD8(+) T-cell immune responses and antitumor effects against an E7-expressing tumor. Since vaccines targeting E6 also represent an important strategy for controlling HPV-associated lesions, we developed a DNA vaccine encoding CRT linked to E6 (CRT/E6). Our results indicated that the CRT/E6 DNA vaccine, but not a wild-type E6 DNA vaccine, generated significant E6-specific CD8(+) T-cell immune responses in vaccinated mice. Mapping of the immunodominant epitope of E6 revealed that an E6 peptide comprising amino acids (aa) 48 to 57 (E6 aa48-57), presented by H-2K(b), is the optimal peptide and that the region of E6 comprising aa 50 to 57 represents the minimal core sequence required for activating E6-specific CD8(+) T lymphocytes. We also demonstrated that E6 aa48-57 contains cytotoxic T-lymphocyte epitopes naturally presented by E6-expressing TC-1 cells. Vaccination with a CRT/E6 but not a CRT/mtE6 (lacking aa 50 to 57 of E6) DNA vaccine could protect vaccinated mice from challenge with E6-expressing TC-1 tumors. Thus, our data indicate that E6 aa48-57 contains the immunodominant epitope and that a CRT/E6 DNA vaccine may be useful for control of HPV infection and HPV-associated lesions.",,"['Peng, Shiwen', 'Ji, Hongxiu', 'Trimble, Cornelia', 'He, Liangmei', 'Tsai, Ya-Chea', 'Yeatermeyer, Jessica', 'Boyd, David A. K.', 'Hung, Chien-Fu', 'Wu, T.-C.']",,,,
,PMC,Human Respiratory Coronavirus OC43: Genetic Stability and Neuroinvasion,http://dx.doi.org/10.1128/JVI.78.16.8824-8834.2004,PMC479063,,,"The complete genome sequences of the human coronavirus OC43 (HCoV-OC43) laboratory strain from the American Type Culture Collection (ATCC), and a HCoV-OC43 clinical isolate, designated Paris, were obtained. Both genomes are 30,713 nucleotides long, excluding the poly(A) tail, and only differ by 6 nucleotides. These six mutations are scattered throughout the genome and give rise to only two amino acid substitutions: one in the spike protein gene (I958F) and the other in the nucleocapsid protein gene (V81A). Furthermore, the two variants were shown to reach the central nervous system (CNS) after intranasal inoculation in BALB/c mice, demonstrating neuroinvasive properties. Even though the ATCC strain could penetrate the CNS more effectively than the Paris 2001 isolate, these results suggest that intrinsic neuroinvasive properties already existed for the HCoV-OC43 ATCC human respiratory isolate from the 1960s before it was propagated in newborn mouse brains. It also demonstrates that the molecular structure of HCoV-OC43 is very stable in the environment (the two variants were isolated ca. 40 years apart) despite virus shedding and chances of persistence in the host. The genomes of the two HCoV-OC43 variants display 71, 53.1, and 51.2% identity with those of mouse hepatitis virus A59, severe acute respiratory syndrome human coronavirus Tor2 strain (SARS-HCoV Tor2), and human coronavirus 229E (HCoV-229E), respectively. HCoV-OC43 also possesses well-conserved motifs with regard to the genome sequence of the SARS-HCoV Tor2, especially in open reading frame 1b. These results suggest that HCoV-OC43 and SARS-HCoV may share several important functional properties and that HCoV-OC43 may be used as a model to study the biology of SARS-HCoV without the need for level three biological facilities.",,"['St-Jean, Julien R.', 'Jacomy, Hélène', 'Desforges, Marc', 'Vabret, Astrid', 'Freymuth, François', 'Talbot, Pierre J.']",,,,
,PMC,Caspases Mediate Processing of the Capsid Precursor and Cell Release of Human Astroviruses,http://dx.doi.org/10.1128/JVI.78.16.8601-8608.2004,PMC479052,,,"In this work we have shown that astrovirus infection induces apoptosis of Caco-2 cells, since fragmentation of cellular DNA, cleavage of cellular proteins which are substrate of activated caspases, and a change in the mitochondrial transmembrane potential occur upon virus infection. The human astrovirus Yuc8 polyprotein capsid precursor VP90 is initially processed to yield VP70, and we have shown that this processing is trypsin independent and occurs intracellularly through four cleavages at its carboxy-terminal region. We further showed that VP90-VP70 processing is mediated by caspases, since it was blocked by the pancaspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (z-VAD-fmk), and it was promoted by the apoptosis inducer TNF-related apoptosis-inducing ligand (TRAIL). Although the cell-associated virus produced in the presence of these compounds was not affected, the release of infectious virus to the cell supernatant was drastically reduced in the presence of z-VAD-fmk and increased by TRAIL, indicating that VP90-VP70 cleavage is important for the virus particles to be released from the cell. This is the first report that describes the induction and utilization of caspase activity by a virus to promote processing of the capsid precursor and dissemination of the viral particles.",,"['Méndez, Ernesto', 'Salas-Ocampo, Elizabeth', 'Arias, Carlos F.']",,,,
,PMC,Regulation of Relative Abundance of Arterivirus Subgenomic mRNAs,http://dx.doi.org/10.1128/JVI.78.15.8102-8113.2004,PMC446141,,,"The subgenomic (sg) mRNAs of arteriviruses (order Nidovirales) form a 5′- and 3′-coterminal nested set with the viral genome. Their 5′ common leader sequence is derived from the genomic 5′-proximal region. Fusion of sg RNA leader and “body” segments involves a discontinuous transcription step. Presumably during minus-strand synthesis, the nascent RNA strand is transferred from one site in the genomic template to another, a process guided by conserved transcription-regulating sequences (TRSs) at these template sites. Subgenomic RNA species are produced in different but constant molar ratios, with the smallest RNAs usually being most abundant. Factors thought to influence sg RNA synthesis are size differences between sg RNA species, differences in sequence context between body TRSs, and the mutual influence (or competition) between strand transfer reactions occurring at different body TRSs. Using an Equine arteritis virus infectious cDNA clone, we investigated how body TRS activity affected sg RNA synthesis from neighboring body TRSs. Flanking sequences were standardized by head-to-tail insertion of several copies of an RNA7 body TRS cassette. A perfect gradient of sg RNA abundance, progressively favoring smaller RNA species, was observed. Disruption of body TRS function by mutagenesis did not have a significant effect on the activity of other TRSs. However, deletion of body TRS-containing regions enhanced synthesis of sg RNAs from upstream TRSs but not of those produced from downstream TRSs. The results of this study provide considerable support for the proposed discontinuous extension of minus-strand RNA synthesis as a crucial step in sg RNA synthesis.",,"['Pasternak, Alexander O.', 'Spaan, Willy J. M.', 'Snijder, Eric J.']",,,,
,PMC,Porcine Arterivirus Infection of Alveolar Macrophages Is Mediated by Sialic Acid on the Virus,http://dx.doi.org/10.1128/JVI.78.15.8094-8101.2004,PMC446125,,,"Recently, we showed that porcine sialoadhesin (pSn) mediates internalization of the arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) in alveolar macrophages (Vanderheijden et al., J. Virol. 77:8207-8215, 2003). In rodents and humans, sialoadhesin, or Siglec-1, has been described as a macrophage-restricted molecule and to specifically bind sialic acid moieties. In the current study, we investigated whether pSn is a sialic acid binding protein and, whether so, whether this property is important for its function as a PRRSV receptor. Using untreated and neuraminidase-treated sheep erythrocytes, we showed that pSn binds sialic acid. Furthermore, pSn-specific monoclonal antibody 41D3, which blocks PRRSV infection, inhibited this interaction. PRRSV attachment to and infection of porcine alveolar macrophages (PAM) were both shown to be dependent on the presence of sialic acid on the virus: neuraminidase treatment of virus but not of PAM blocked infection and reduced attachment. Enzymatic removal of all N-linked glycans on the virus with N-glycosidase F reduced PRRSV infection, while exclusive removal of nonsialylated N-linked glycans of the high-mannose type with endoglycosidase H had no significant effect. Free sialyllactose and sialic acid containing (neo)glycoproteins reduced infection, while lactose and (neo)glycoproteins devoid of sialic acids had no significant effect. Studies with linkage-specific neuraminidases and lectins indicated that α2-3- and α2-6-linked sialic acids on the virion are important for PRRSV infection of PAM. From these results, we conclude that pSn is a sialic acid binding lectin and that interactions between sialic acid on the PRRS virion and pSn are essential for PRRSV infection of PAM.",,"['Delputte, Peter L.', 'Nauwynck, Hans J.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Phylogeny: toward Consensus,http://dx.doi.org/10.1128/JVI.78.15.7863-7866.2004,PMC446116,,,,,"['Gorbalenya, Alexander E.', 'Snijder, Eric J.', 'Spaan, Willy J. M.']",,,,
,PMC,Epitope Mapping of the Major Capsid Protein of Type 2 Porcine Circovirus (PCV2) by Using Chimeric PCV1 and PCV2,http://dx.doi.org/10.1128/JVI.78.15.8135-8145.2004,PMC446101,,,"Type 2 porcine circovirus (PCV2) is associated with postweaning multisystemic wasting syndrome in pigs, whereas the genetically related type 1 PCV (PCV1) is nonpathogenic. In this study, seven monoclonal antibodies (MAbs) against PCV2-ORF2 capsid protein were generated, biologically characterized, and subsequently used to map the antigenic sites of PCV2 capsid protein by using infectious PCV DNA clones containing PCV1/PCV2-ORF2 chimeras. The PCV1/PCV2-ORF2 chimeras were constructed by serial deletions of PCV2-ORF2 and replacement with the corresponding sequences of the PCV1-ORF2. The reactivities of chimeric PCV1/PCV2 clones in transfected PK-15 cells with the seven MAbs were detected by an immunofluorescence assay (IFA). The chimera (r140) with a deletion of 47 amino acids at the N terminus of PCV2-ORF2 reacted strongly to all seven MAbs. Expanding the deletion of PCV2-ORF2 from residues 47 to 57 (r175) abolished the recognition of MAb 3B7, 3C11, 4A10, 6H2, or 8F6 to the chimera. Further deletion of PCV2-ORF2 to 62 residues disrupted the binding of this chimera to all seven MAbs. IFA reactivities with all MAbs were absent when residues 165 to 233 at the C terminus of PCV2-ORF2 was replaced with that of PCV1-ORF2. Extending the sequence of PCV2-ORF2 from residues 165 (r464) to 185 (r526), 200 (r588), or 224 (r652) restored the ability of the three chimeras to react with MAbs 3C11, 6H2, 9H7, and 12G3 but not with 8F6, 3B7, or 4A10. When the four amino acids at the C terminus of r588 were replaced with that of PCV2-ORF2, the resulting chimera (r588F) reacted with all seven MAbs. The results from this study suggest that these seven MAbs recognized at least five different but overlapping conformational epitopes within residues 47 to 63 and 165 to 200 and the last four amino acids at the C terminus of the PCV2 capsid protein.",,"['Lekcharoensuk, Porntippa', 'Morozov, Igor', 'Paul, Prem S.', 'Thangthumniyom, Nattarat', 'Wajjawalku, Worawidh', 'Meng, X. J.']",,,,
,PMC,Functional Antagonism of Chemokine Receptor CCR1 Reduces Mortality in Acute Pneumovirus Infection In Vivo,http://dx.doi.org/10.1128/JVI.78.15.7984-7989.2004,PMC446089,,,"We present an antiviral-immunomodulatory therapeutic strategy involving the chemokine receptor antagonist Met-RANTES, which yields significant survival in the setting of an otherwise fatal respiratory virus infection. In previous work, we demonstrated that infection with the natural rodent pathogen pneumonia virus of mice involves robust virus replication accompanied by cellular inflammation modulated by the CC chemokine macrophage inflammatory protein 1α (MIP-1α). We found that the antiviral agent ribavirin limited virus replication in vivo but had no impact on morbidity and mortality associated with this disease in the absence of immunomodulatory control. We show here that ribavirin reduces mortality, from 100% to 10 and 30%, respectively, in gene-deleted CCR1(−/−) mice and in wild-type mice treated with the small-molecule chemokine receptor antagonist, Met-RANTES. As MIP-1α-mediated inflammation is a common response to several distantly related respiratory virus pathogens, specific antiviral therapy in conjunction with blockade of the MIP-1α/CCR1 inflammatory cascade may ultimately prove to be a useful, generalized approach to severe respiratory virus infection and its pathological sequelae in human subjects.",,"['Bonville, Cynthia A.', 'Lau, Vincent K.', 'DeLeon, Jordana M.', 'Gao, Ji-Liang', 'Easton, Andrew J.', 'Rosenberg, Helene F.', 'Domachowske, Joseph B.']",,,,
,PMC,Consumption of milk fat and reduced asthma risk in pre-school children,,PMC1747115,,,,,"['Karmaus, W', 'Fussman, C', 'Wijga, A', 'Boshuizen, H', 'Smit, H', 'Kerkhof, M', 'Gerritsen, J', 'de Jongste, J C', 'Neijens, H', 'Brunekreef, B']",,,,
,PMC,Antiviral agents and corticosteroids in the treatment of severe acute respiratory syndrome (SARS),http://dx.doi.org/10.1136/thx.2003.017665,PMC1747111,,,,,"['Yu, W', 'Hui, D', 'Chan-Yeung, M']",,,,
,PMC,Regulation: the art of control? Regulatory T cells and asthma and allergy,http://dx.doi.org/10.1136/thx.2003.019166,PMC1747096,,,,,"Robinson, D",,,,
,PMC,Urinary leukotriene LTE(4) levels in non-responders to antileukotriene therapy,,PMC1747093,,,,,"['Lee, D', 'Green, S']",,,,
,PMC,BIS/BTS SARS guidelines,,PMC1747089,,,,,"['Lange, J', 'Anderson, S', 'Lim, W']",,,,
,PMC,In brief,,PMC498014,,,,,,,,,
,PMC,A complex network of RNA–RNA interactions controls subgenomic mRNA transcription in a tombusvirus,http://dx.doi.org/10.1038/sj.emboj.7600336,PMC514510,,,"Eukaryotic (+)-strand RNA viruses utilize a wide variety of gene expression strategies to achieve regulated production of their viral proteins. A common mechanism used by many is to transcribe viral subgenomic (sg) mRNAs. Transcription of sg mRNA2 in tombusviruses allows for expression of the p19 suppressor of gene silencing and p22 movement proteins. We have investigated the mechanism of transcription of this sg mRNA in Tomato bushy stunt virus and have determined that this process is facilitated by no less than three different RNA modules that are located throughout the viral genome. These RNA units perform distinct tasks and function via long-distance RNA–RNA interactions. Systematic deconstruction of the RNA network and analysis of related RNA promoter elements allowed us to identify fundamental properties necessary for productive sg mRNA2 transcription. Collectively, our results (i) establish specific roles for the different RNA components of a multipartite RNA-based control system, (ii) support a premature termination mechanism for tombusvirus sg mRNA transcription and (iii) reveal a close mechanistic relationship between sg mRNA transcription, viral RNA replication and RNA recombination.",,"['Lin, Han-Xin', 'White, K Andrew']",,,,
,PMC,Influenza as a model system for studying the cross-species transfer and evolution of the SARS coronavirus.,http://dx.doi.org/10.1098/rstb.2004.1481,PMC1693400,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) moved into humans from a reservoir species and subsequently caused an epidemic in its new host. We know little about the processes that allowed the cross-species transfer of this previously unknown virus. I discuss what we have learned about the movement of viruses into humans from studies of influenza A, both how it crossed from birds to humans and how it subsequently evolved within the human population. Starting with a brief review of severe acute respiratory syndrome to highlight the kinds of problems we face in learning about this viral disease, I then turn to influenza A, focusing on three topics. First, I present a reanalysis of data used to test the hypothesis that swine served as a ""mixing vessel"" or intermediate host in the transmission of avian influenza to humans during the 1918 ""Spanish flu"" pandemic. Second, I review studies of archived viruses from the three recent influenza pandemics. Third, I discuss current limitations in using molecular data to study the evolution of infectious disease. Although influenza A and SARS-CoV differ in many ways, our knowledge of influenza A may provide important clues about what limits or favours cross-species transfers and subsequent epidemics of newly emerging pathogens.",,"Bush, Robin M",,,,
,PMC,Laboratory diagnosis of SARS.,http://dx.doi.org/10.1098/rstb.2004.1493,PMC1693399,,,"The emergence of new viral infections of man requires the development of robust diagnostic tests that can be applied in the differential diagnosis of acute illness, or to determine past exposure, so as to establish the true burden of disease. Since the recognition in April 2003 of the severe acute respiratory syndrome coronavirus (SARS-CoV) as the causative agent of severe acute respiratory syndrome (SARS), enormous efforts have been applied to develop molecular and serological tests for SARS which can assist rapid detection of cases, accurate diagnosis of illness and the application of control measures. International progress in the laboratory diagnosis of SARS-CoV infection during acute illness has led to internationally agreed World Health Organization criteria for the confirmation of SARS. Developments in the dissection of the human immune response to SARS indicate that serological tests on convalescent sera are essential to confirm SARS infection, given the sub-optimal predictive value of molecular detection tests performed during acute SARS illness.",,"['Bermingham, A', 'Heinen, P', 'Iturriza-Gómara, M', 'Gray, J', 'Appleton, H', 'Zambon, M C']",,,,
,PMC,Management and prevention of SARS in China.,http://dx.doi.org/10.1098/rstb.2004.1491,PMC1693398,,,"The case fatality was the lowest (3.8%) among 1512 cases with severe acute respiratory syndrome (SARS) in Guangdong Province, China. Rational use of corticosteroid, non-invasive ventilation and the integration of traditional Chinese medicine and modern medicine may partly have contributed to the lowest fatality figure. There was a close linkage between civet cats and humans in terms of transmission of SARS. Strict control of the wild-animal market may be significant in preventing a new outbreak of SARS this year.",,"Zhong, Nanshan",,,,
,PMC,Introduction. Emerging infections: what have we learnt from SARS?,http://dx.doi.org/10.1098/rstb.2004.1488,PMC1693397,,,,,"['McLean, A R', 'May, R M', 'Pattison, J', 'Weiss, R A']",,,,
,PMC,Preparedness for SARS in the UK in 2003.,http://dx.doi.org/10.1098/rstb.2004.1485,PMC1693396,,,"Severe acute respiratory syndrome (SARS) has been described as the first major emerging infectious disease of the twenty-first century. Having initially emerged, almost unnoticed, in southern China, it rapidly spread across the globe. It severely tested national public health and health systems. However, it also resulted in rapid, intensive international collaboration, led by the World Health Organization, to elucidate its characteristics and cause and to contain its spread. The UK mounted a vigorous public health response. Some particular issues concerned: the practicalities of implementing exit screening had this been required; the likely efficacy of this and other control measures; the legal base for public health action; and the surge capacity in all systems should the disease have taken hold in the UK. We have used this experience of 2003 to inform our preparation of a framework for an integrated, escalating response to a future re-emergence of SARS according to the levels of disease activity worldwide. Recent cases confirm that SARS has not ""gone away"". We cannot be complacent about our contingency planning.",,"Harper, David R",,,,
,PMC,Viral evolution and the emergence of SARS coronavirus.,http://dx.doi.org/10.1098/rstb.2004.1478,PMC1693395,,,"The recent appearance of severe acute respiratory syndrome coronavirus (SARS-CoV) highlights the continual threat to human health posed by emerging viruses. However, the central processes in the evolution of emerging viruses are unclear, particularly the selection pressures faced by viruses in new host species. We outline some of the key evolutionary genetic aspects of viral emergence. We emphasize that, although the high mutation rates of RNA viruses provide them with great adaptability and explain why they are the main cause of emerging diseases, their limited genome size means that they are also subject to major evolutionary constraints. Understanding the mechanistic basis of these constraints, particularly the roles played by epistasis and pleiotropy, is likely to be central in explaining why some RNA viruses are more able than others to cross species boundaries. Viral genetic factors have also been implicated in the emergence of SARS-CoV, with the suggestion that this virus is a recombinant between mammalian and avian coronaviruses. We show, however, that the phylogenetic patterns cited as evidence for recombination are more probably caused by a variation in substitution rate among lineages and that recombination is unlikely to explain the appearance of SARS in humans.",,"['Holmes, Edward C', 'Rambaut, Andrew']",,,,
,PMC,The aetiology of SARS: Koch's postulates fulfilled.,http://dx.doi.org/10.1098/rstb.2004.1489,PMC1693394,,,"Proof that a newly identified coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV) is the primary cause of severe acute respiratory syndrome (SARS) came from a series of studies on experimentally infected cynomolgus macaques (Macaca fascicularis). SARS-CoV-infected macaques developed a disease comparable to SARS in humans; the virus was re-isolated from these animals and they developed SARS-CoV-specific antibodies. This completed the fulfilment of Koch's postulates, as modified by Rivers for viral diseases, for SARS-CoV as the aetiological agent of SARS. Besides the macaque model, a ferret and a cat model for SARS-CoV were also developed. These animal models allow comparative pathogenesis studies for SARS-CoV infections and testing of different intervention strategies. The first of these studies has shown that pegylated interferon-alpha, a drug approved for human use, limits SARS-CoV replication and lung damage in experimentally infected macaques. Finally, we argue that, given the worldwide nature of the socio-economic changes that have predisposed for the emergence of SARS and avian influenza in Southeast Asia, such changes herald the beginning of a global trend for which we are ill prepared.",,"['Osterhaus, A D M E', 'Fouchier, R A M', 'Kuiken, T']",,,,
,PMC,Animal origins of SARS coronavirus: possible links with the international trade in small carnivores.,http://dx.doi.org/10.1098/rstb.2004.1492,PMC1693393,,,"The search for animal host origins of severe acute respiratory syndrome (SARS) coronavirus has so far remained focused on wildlife markets, restaurants and farms within China. A significant proportion of this wildlife enters China through an expanding regional network of illegal, international wildlife trade. We present the case for extending the search for ancestral coronaviruses and their hosts across international borders into countries such as Vietnam and Lao People's Democratic Republic, where the same guilds of species are found on sale in similar wildlife markets or food outlets. The three species that have so far been implicated, a viverrid, a mustelid and a canid, are part of a large suite of small carnivores distributed across this region currently overexploited by this international wildlife trade. A major lesson from SARS is that the underlying roots of newly emergent zoonotic diseases may lie in the parallel biodiversity crisis of massive species loss as a result of overexploitation of wild animal populations and the destruction of their natural habitats by increasing human populations. To address these dual threats to the long-term future of biodiversity, including man, requires a less anthropocentric and more interdisciplinary approach to problems that require the combined research expertise of ecologists, conservation biologists, veterinarians, epidemiologists, virologists, as well as human health professionals.",,"['Bell, Diana', 'Roberton, Scott', 'Hunter, Paul R']",,,,
,PMC,The international response to the outbreak of SARS in 2003.,http://dx.doi.org/10.1098/rstb.2004.1484,PMC1693392,,,"The sudden arrival of an internationally spreading outbreak of a newly identified infectious disease in early 2003, severe acute respiratory syndrome (SARS), provided an opportunity for a coordinated international response based on information and evidence obtained in real time through standard and electronic communications. Its containment represents a new way of working internationally, and demonstrates how intense collaboration in virology, clinical medicine and epidemiology can rapidly provide the information necessary to create and implement evidence-based control measures. The SARS outbreak serves as a reminder of the need for a strong national surveillance and response to infectious diseases, evidence-based international travel recommendations, and a global alert and response network to serve as a safety net when national surveillance fails.",,"Heymann, David L",,,,
,PMC,What have we learnt from SARS?,http://dx.doi.org/10.1098/rstb.2004.1487,PMC1693391,,,"With outbreaks of infectious disease emerging from animal sources, we have learnt to expect the unexpected. We were, and are, expecting a new influenza A pandemic, but no one predicted the emergence of an unknown coronavirus (CoV) as a deadly human pathogen. Thanks to the preparedness of the international network of influenza researchers and laboratories, the cause of severe acute respiratory syndrome (SARS) was rapidly identified, but there is no complacency over the global or local management of the epidemic in terms of public health logistics. The human population was lucky that only a small proportion of infected persons proved to be highly infectious to others, and that they did not become so before they felt ill. These were the features that helped to make the outbreak containable. The next outbreak of another kind of transmissible disease may well be quite different.",,"['Weiss, Robin A', 'McLean, Angela R']",,,,
,PMC,Confronting SARS: a view from Hong Kong.,http://dx.doi.org/10.1098/rstb.2004.1482,PMC1693390,,,"Severe acute respiratory syndrome (SARS) emerged as a new disease in Guangdong Province, People's Republic of China in late 2002. Within weeks it had spread to Hong Kong and thence globally to affect over 25 countries across five continents. The disease had the propensity to cause clusters of pneumonia, particularly in healthcare workers or close family contacts. A global effort coordinated by the World Health Organization successfully defined the aetiology, epidemiology and clinical characteristics of the disease, and the implementation of case identification, isolation and infection control measures led to the interruption of the global outbreak by July 2003. The pattern of disease emergence and strategies for control of SARS provides lessons for coping with future emerging infectious disease threats.",,"['Peiris, J S M', 'Guan, Y']",,,,
,PMC,"Epidemiology, transmission dynamics and control of SARS: the 2002-2003 epidemic.",http://dx.doi.org/10.1098/rstb.2004.1490,PMC1693389,,,"This paper reviews current understanding of the epidemiology, transmission dynamics and control of the aetiological agent of severe acute respiratory syndrome (SARS). We present analyses of data on key parameters and distributions and discuss the processes of data capture, analysis and public health policy formulation during the SARS epidemic are discussed. The low transmissibility of the virus, combined with the onset of peak infectiousness following the onset of clinical symptoms of disease, transpired to make simple public health measures, such as isolating patients and quarantining their contacts, very effective in the control of the SARS epidemic. We conclude that we were lucky this time round, but may not be so with the next epidemic outbreak of a novel aetiological agent. We present analyses that help to further understanding of what intervention measures are likely to work best with infectious agents of defined biological and epidemiological properties. These lessons learnt from the SARS experience are presented in an epidemiological and public health context.",,"['Anderson, Roy M', 'Fraser, Christophe', 'Ghani, Azra C', 'Donnelly, Christl A', 'Riley, Steven', 'Ferguson, Neil M', 'Leung, Gabriel M', 'Lam, T H', 'Hedley, Anthony J']",,,,
,PMC,The experience of the 2003 SARS outbreak as a traumatic stress among frontline healthcare workers in Toronto: lessons learned.,http://dx.doi.org/10.1098/rstb.2004.1483,PMC1693388,,,"The outbreak of severe acute respiratory syndrome (SARS) in the first half of 2003 in Canada was unprecedented in several respects. Understanding the psychological impact of the outbreak on healthcare workers, especially those in hospitals, is important in planning for future outbreaks of emerging infectious diseases. This review draws upon qualitative and quantitative studies of the SARS outbreak in Toronto to outline the factors that contributed to healthcare workers' experiencing the outbreak as a psychological trauma. Overall, it is estimated that a high degree of distress was experienced by 29-35% of hospital workers. Three categories of contributory factors were identified. Relevant contextual factors were being a nurse, having contact with SARS patients and having children. Contributing attitudinal factors and processes were experiencing job stress, perceiving stigmatization, coping by avoiding crowds and colleagues, and feeling scrutinized. Pre-existing trait factors also contributed to vulnerability. Lessons learned from the outbreak include: (i) that effort is required to mitigate the psychological impact of infection control procedures, especially the interpersonal isolation that these procedures promote; (ii) that effective risk communication is a priority early in an outbreak; (iii) that healthcare workers may have a role in influencing patterns of media coverage that increase or decrease morale; (iv) that healthcare workers benefit from resources that facilitate reflection on the effects of extraordinary stressors; and (v) that healthcare workers benefit from practical interventions that demonstrate tangible support from institutions.",,"Maunder, Robert",,,,
,PMC,"Environmental and social influences on emerging infectious diseases: past, present and future.",http://dx.doi.org/10.1098/rstb.2004.1480,PMC1693387,,,"During the processes of human population dispersal around the world over the past 50 000-100 000 years, along with associated cultural evolution and inter-population contact and conflict, there have been several major transitions in the relationships of Homo sapiens with the natural world, animate and inanimate. Each of these transitions has resulted in the emergence of new or unfamiliar infectious diseases.The three great historical transitions since the initial advent of agriculture and livestock herding, from ca. 10 000 years ago, occurred when: (i) early agrarian-based settlements enabled sylvatic enzootic microbes to make contact with Homo sapiens; (ii) early Eurasian civilizations (such as the Greek and Roman empires, China and south Asia) came into military and commercial contact, ca. 3000-2000 years ago, swapping their dominant infections; and (iii) European expansionism, over the past five centuries, caused the transoceanic spread of often lethal infectious diseases. This latter transition is best known in relation to the conquest of the Americas by Spanish conquistadores, when the inadvertent spread of measles, smallpox and influenza devastated the Amerindian populations.Today, we are living through the fourth of these great transitional periods. The contemporary spread and increased lability of various infectious diseases, new and old, reflect the combined and increasingly widespread impacts of demographic, environmental, behavioural, technological and other rapid changes in human ecology. Modern clinical medicine has, via blood transfusion, organ transplantation, and the use of hypodermic syringes, created new opportunities for microbes. These have contributed to the rising iatrogenic problems of hepatitis C, HIV/AIDS and several other viral infections. Meanwhile, the injudicious use of antibiotics has been a rare instance of human action actually increasing 'biodiversity'.Another aspect of this fourth transition is that modern hyper-hygienic living restricts microbial exposure in early life. This, in the 1950s, may have contributed to an epidemic of more serious, disabling, poliomyelitis, affecting older children than those affected in earlier, more endemic decades. As with previous human-microbe transitions, a new equilibrial state may lie ahead. However, it certainly will not entail a world free of infectious diseases. Any mature, sustainable, human ecology must come to terms with both the need for, and the needs of, the microbial species that help to make up the interdependent system of life on Earth. Humans and microbes are not ""at war""; rather, both parties are engaged in amoral, self-interested, coevolutionary struggle. We need to understand better, and therefore anticipate, the dynamics of that process.",,"McMichael, A J",,,,
,PMC,Informed consent and public health.,http://dx.doi.org/10.1098/rstb.2004.1486,PMC1693386,,,"During the past 25 years, medical ethics has concentrated largely on clinical medicine and the treatment of individual patients. This focus permits a view of medical provision as a (quasi-) consumer good, whose distribution can be or should be contingent on individual choice. The approach cannot be extended to public health provision. Public health provision, including measures for limiting the spread of infectious diseases, is a public good and can be provided for some only if provided for many. The provision or non-provision of public goods cannot be contingent on individual informed consent, so must be in some respects compulsory. An adequate ethics of public health needs to set aside debates about informed consent and to consider the permissible limits of just compulsion for various types of public good. It will therefore gain more from engaging with work in political philosophy than with individualistic work in ethics.",,"O'Neill, Onora",,,,
,PMC,"Alternate, virus-induced membrane rearrangements support positive-strand RNA virus genome replication",http://dx.doi.org/10.1073/pnas.0404157101,PMC509192,,,"All positive-strand RNA [(+)RNA] viruses replicate their RNA on intracellular membranes, often in association with spherular invaginations of the target membrane. For brome mosaic virus, we previously showed that such spherules serve as compartments or mini-organelles for RNA replication and that their assembly, structure, and function have similarities to the replicative cores of retrovirus and double-stranded RNA virus virions. Some other (+)RNA viruses conduct RNA replication in association with individual or clustered double-membrane vesicles, appressed double membranes, or other structures whose possible relationships to the spherular invaginations are unclear. Here we show that modulating the relative levels and interactions of brome mosaic virus replication factors 1a and 2a polymerase (2a(pol)) shifted the membrane rearrangements associated with RNA replication from small invaginated spherules to large, karmellae-like, multilayer stacks of appressed double membranes that supported RNA replication as efficiently as spherules. Spherules were induced by expressing 1a, which has functional similarities to retrovirus virion protein Gag, or 1a plus low levels of 2a(pol). Double-membrane layers were induced by 1a plus higher levels of 2a(pol) and were suppressed by deleting the major 1a-interacting domain from 2a(pol). The stacked, double-membrane layers alternated with spaces that, like spherule interiors, were 50–60 nm wide, connected to the cytoplasm, and contained 1a and 2a(pol). These and other results suggest that seemingly diverse membrane rearrangements associated with RNA replication by varied (+)RNA viruses may represent topologically and functionally related structures formed by similar protein–protein and protein–membrane interactions and interconverted by altering the balances among those interactions.",,"['Schwartz, Michael', 'Chen, Jianbo', 'Lee, Wai-Ming', 'Janda, Michael', 'Ahlquist, Paul']",,,,
,PMC,Chinese government detains doctor who criticised it,,PMC478255,,,,,"Parry, Jane",,,,
,PMC,Two Hong Kong politicians resign in wake of SARS report,,PMC478253,,,,,"Parry, Jane",,,,
,PMC,The manipulation of immunity,http://dx.doi.org/10.1038/sj.embor.7400204,PMC1299115,,,Conference on From Allergy to Cancer: New Perspectives for Therapeutic Vaccination,,"['von Boehmer, Harald', 'Nussenzweig, Michel C.']",,,,
,PMC,Discovery of antivirals against smallpox,http://dx.doi.org/10.1073/pnas.0403600101,PMC509180,,,,,"['Harrison, Stephen C.', 'Alberts, Bruce', 'Ehrenfeld, Ellie', 'Enquist, Lynn', 'Fineberg, Harvey', 'McKnight, Steven L.', 'Moss, Bernard', ""O'Donnell, Michael"", 'Ploegh, Hidde', 'Schmid, Sandra L.', 'Walter, K. Peter', 'Theriot, Julie']",,,,
,PMC,Harnessing new science is vital for biodefense and global health,http://dx.doi.org/10.1073/pnas.0404433101,PMC509179,,,,,"['Alberts, Bruce', 'Fineberg, Harvey V.']",,,,
,PMC,The New Global Threat: Severe Acute Respiratory Syndrome and its Impacts,,PMC449834,,,,,"Kirk, Richard",,,,
,PMC,Severe acute respiratory syndrome and its impact on professionalism: qualitative study of physicians' behaviour during an emerging healthcare crisis,http://dx.doi.org/10.1136/bmj.38127.444838.63,PMC449811,,,"Objective To explore issues of medical professionalism in the context of severe acute respiratory syndrome (SARS), a new emerging health threat. Design Qualitative interviews analysed with grounded theory methodology. Setting University hospitals in Toronto, Canada, during the SARS outbreak in 2003. Participants 14 staff physicians from divisions of infectious diseases, general internal medicine, and critical care medicine. Results Of 14 attending physicians, four became ill during the outbreak. Participants described their experiences during the outbreak and highlighted several themes about values inherent to medical professionalism that arose during this crisis including the balance between care of patients and accepted personal risk, confidentiality, appropriate interactions between physicians and patients, ethical research conduct, and role modelling of professionalism for junior doctors. Conclusion Despite concerns raised by professional societies about the erosion of professionalism, participants in this study amply demonstrated the necessary qualities during the recent healthcare crisis. However, there were several examples of strained professional behaviour witnessed by the participants and these examples highlight aspects of medical professionalism that medical educators and professional organisations should address in the future, including the balance between personal safety and duty of care.",,"['Straus, Sharon E', 'Wilson, Kumanan', 'Rambaldini, Gloria', 'Rath, Darlyne', 'Lin, Yulia', 'Gold, Wayne L', 'Kapral, Moira K']",,,,
,PMC,Ethical Challenges in Preparing for Bioterrorism: Barriers Within the Health Care System,,PMC1448404,,,"Preparedness for bioterrorism poses significant ethical challenges. Although public health ethics and preparedness have received attention recently, health care ethics must also be considered. In epidemics, the health care system assists public health in 3 tasks: detection, containment, and treatment. Detection might fail if all patients do not have access to care, or if physicians do not understand their obligation to report infectious diseases to public health authorities. Containment might fail if physicians view themselves only as advocates for individual patients, ignoring their social obligations as health professionals. Treatment might fail if physicians do not accept their professional duty to treat patients during epidemics. Each of these potential ethical barriers to preparedness must be addressed by physicians and society.",,"['Wynia, Matthew K.', 'Gostin, Lawrence O.']",,,,
,PMC,Legal and Public Policy Responses of States to Bioterrorism,,PMC1448403,,,"In late 2001, during the aftermath of the anthrax letter attacks, model legislation was proposed to relevant state agencies to update their states’ public health laws to meet the threat of bioterrorism. This legislation was the Model State Emergency Health Powers Act. A concern underlying this and related efforts to address future bioterrorism threats was the perceived inadequacy of state laws to respond effectively when such threats occur. We evaluated how 4 states—Utah, Maine, South Dakota, and Indiana—addressed this concern in the context of the model legislation. The conclusion is that the model legislation generally served as an important catalyst for state action in the field of bioterrorism preparation.",,"Martin, William",,,,
,PMC,Inhibition of Severe Acute Respiratory Syndrome Coronavirus Replication by Niclosamide,http://dx.doi.org/10.1128/AAC.48.7.2693-2696.2004,PMC434198,,,"Antiviral agents are urgently needed to fight severe acute respiratory syndrome (SARS). We showed that niclosamide, an existing antihelminthic drug, was able to inhibit replication of a newly discovered coronavirus, SARS-CoV; viral antigen synthesis was totally abolished at a niclosamide concentration of 1.56 μM, as revealed by immunoblot analysis. Thus, niclosamide represents a promising drug candidate for the effective treatment of SARS-CoV infection.",,"['Wu, Chang-Jer', 'Jan, Jia-Tsrong', 'Chen, Chi-Min', 'Hsieh, Hsing-Pang', 'Hwang, Der-Ren', 'Liu, Hwan-Wun', 'Liu, Chiu-Yi', 'Huang, Hui-Wen', 'Chen, Su-Chin', 'Hong, Cheng-Fong', 'Lin, Ren-Kuo', 'Chao, Yu-Sheng', 'Hsu, John T. A.']",,,,
,PMC,Tears and conjunctival scrapings for coronavirus in patients with SARS,http://dx.doi.org/10.1136/bjo.2003.039461,PMC1772218,,,,,"['Chan, W M', 'Yuen, K S C', 'Fan, D S P', 'Lam, D S C', 'Chan, P K S', 'Sung, J J Y']",,,,
,PMC,BJO at a glance,,PMC1772217,,,,,"Hoyt, Creig",,,,
,PMC,The severe acute respiratory syndrome coronavirus in tears,http://dx.doi.org/10.1136/bjo.2003.035931,PMC1772213,,,"Background: Severe acute respiratory syndrome (SARS) is a new infectious disease that caused a global outbreak in 2003. Research has shown that it is caused by a novel coronavirus. A series of cases is reported where polymerase chain reaction (PCR) testing on tears had demonstrated the presence of the virus. Detection of ocular infection from tears using the PCR technique has been widely used by ophthalmologists to diagnose infections for other viruses. Methods: This is a case series report from cases classified as probable or suspect SARS cases. Tear samples were collected from 36 consecutive patients who were suspected of having SARS in Singapore over a period of 12 days (7–18 April 2003), and analysed by PCR using protocols developed by the WHO network of laboratories. Results: Three patients with probable SARS (one female and two male patients) had positive results from their tear samples. Tear samples were used to confirm SARS in the female patient, who was positive only from her tears. The positive specimens were found in cases sampled early in their course of infection. Conclusions: This is the first case series reported with the detection of the SARS coronavirus from tears, and has important implications for the practice of ophthalmology and medicine. The ability to detect and isolate the virus in the early phase of the disease may be an important diagnostic tool for future patients and tear sampling is both simple and easily repeatable. Many healthcare workers are in close proximity to the eyes of patients and this may be a source of spread among healthcare workers and inoculating patients. Ophthalmic practices may need to change as more stringent barrier methods, appropriate quarantine, and isolation measures are vital when managing patients with SARS.",,"['Loon, S-C', 'Teoh, S C B', 'Oon, L L E', 'Se-Thoe, S-Y', 'Ling, A-E', 'Leo, Y-S', 'Leong, H-N']",,,,
,PMC,Changing virulence of the SARS virus: the epidemiological evidence.,,PMC2622914,,,,,"['Wang, Ming-Dong', 'Jolly, Ann Margaret']",,,,
,PMC,Financing and organization of China's health care.,,PMC2622900,,,,,"Hu, Teh-wei",,,,
,PMC,China's public health-care system: facing the challenges.,,PMC2622899,,,"The severe acute respiratory syndrome (SARS) crisis in China revealed not only the failures of the Chinese health-care system but also some fundamental structural deficiencies. A decentralized and fragmented health system, such as the one found in China, is not well-suited to making a rapid and coordinated response to public health emergencies. The commercial orientation of the health sector on the supply-side and lack of health insurance coverage on the demand-side further exacerbate the problems of the under-provision of public services, such as health surveillance and preventive care. For the past 25 years, the Chinese Government has kept economic development at the top of the policy agenda at the expense of public health, especially in terms of access to health care for the 800 million people living in rural areas. A significant increase in government investment in the public health infrastructure, though long overdue, is not sufficient to solve the problems of the health-care system. China needs to reorganize its public health system by strengthening both the vertical and horizontal connections between its various public health organizations. China's recent policy of establishing a matching-fund financed rural health insurance system presents an exciting opportunity to improve people's access to health care.",,"Liu, Yuanli",,,,
,PMC,The costs and consequences of methicillin-resistant Staphylococcus aureus infection treatments in Canada,,PMC2094976,,,"BACKGROUND: A multinational randomized controlled trial has shown a trend toward early discharge of patients taking oral linezolid versus intravenous vancomycin (IV) in the treatment of methicillinresistant Staphylococcus aureus (MRSA) infections. Infection treatments resulting in shorter hospitalization durations are associated with cost savings from the hospital perspective. OBJECTIVE: To determine whether similar economic advantages are associated with oral linezolid, the costs and consequences of linezolid use following vancomycin IV versus the existing practice in the treatment of infections caused by MRSA were compared. METHODS: The charts of all patients admitted to one of three tertiary care teaching hospitals between January 1, 1997 and August 31, 2000 and treated with vancomycin IV for an active MRSA infection (skin and soft tissue only) were reviewed. Based on the vancomycin IV chart review data set and a simulated linezolid data set, the clinical consequences and the associated costs of MRSA treatment with vancomycin IV, and oral and IV forms of linezolid were quantified and compared within the framework of a cost-consequence analysis. RESULTS: Patients treated with oral and IV forms of linezolid compared with the existing practice had a shorter length of stay and required fewer home IV care services, which resulted in a cost savings of $750 (2001 values) to the Canadian health care perspective. CONCLUSIONS: The estimated cost savings associated with linezolid use not only offset the higher acquisition cost of the anti-infective, but may be substantial to health care systems across Canada, especially as the incidence of MRSA continues to rise.",,"['Rosner, Andrew J', 'Becker, Debbie L', 'Wong, Angelina H', 'Miller, Elizabeth', 'Conly, John M']",,,,
,PMC,Severe acute respiratory syndrome: Did quarantine help?,,PMC2094974,,,,,"Schabas, Richard",,,,
,PMC,Wearing Masks in a Pediatric Hospital: Developing Practical Guidelines,http://dx.doi.org/10.1007/BF03405126,PMC6976022,,,,,"['Beck, Marcia', 'Antle, Beverley J.', 'Berlin, Deborah', 'Granger, Miriam', 'Meighan, Kimberley', 'Neilson, Barbara J.', 'Shama, Wendy', 'Westland, John', 'Kaufman, Miriam']",,,,
,PMC,Eucaryotic Expression of the Nucleocapsid Protein Gene of Porcine Circovirus Type 2 and Use of the Protein in an Indirect Immunofluorescence Assay for Serological Diagnosis of Postweaning Multisystemic Wasting Syndrome in Pigs,http://dx.doi.org/10.1128/CDLI.11.4.736-741.2004,PMC440625,,,"The purpose of this study was to develop a sensitive, rapid, and inexpensive immunofluorescence assay (IFA) using a recombinant porcine circovirus type 2 (PCV2) nucleocapsid protein for the serological detection of PCV2-specific antibodies in pig sera. The viral nucleocapsid protein encoded by the PCV2 ORF2 gene has recently been identified as the most immunoreactive viral protein that carries type-specific antigenic determinants. The ORF2 sequence of the IAF-2897 strain of PCV2 has been cloned into a pCEP5 eucaryotic expression vector under the control of the cytomegalovirus promoter, downstream of a polyhistidine sequence tag. The recombinant plasmid was used in transfection experiments with human epithelial kidney 293 cells that were further tested, and positive expression of the viral nucleocapsid protein was confirmed by IFA and Western blotting. Strong, specific fluorescence was observed in the nuclei of transfected cells. Test specificity to PCV2 was verified with several related infectious agents. Sensitivity was compared to that of standard IFA using PCV2-infected cells by evaluating the reactivities of 44 field serum samples from pigs on farms with a porcine population suffering from postweaning multisystemic wasting syndrome. The recombinant nucleocapsid-based test was able to detect 15 more positive-testing pigs than the PCV2-based IFA. Therefore, the relative sensitivity of the latter test was estimated at only 57.1% compared to that of the recombinant nucleocapsid-based test. The recombinant fusion protein has been purified by affinity chromatography and is being used to develop further sensitive serological tests.",,"['Racine, Sébastien', 'Kheyar, Ali', 'Gagnon, Carl A.', 'Charbonneau, Benoît', 'Dea, Serge']",,,,
,PMC,Kinetics of Severe Acute Respiratory Syndrome (SARS) Coronavirus-Specific Antibodies in 271 Laboratory-Confirmed Cases of SARS,http://dx.doi.org/10.1128/CDLI.11.4.792-794.2004,PMC440623,,,"The sensitivities and specificities of an immunofluorescence assay and an enzyme immunoassay for detection of antibodies specific for severe acute respiratory syndrome coronavirus (SARS-CoV) were compared for 148 laboratory-confirmed SARS cases. The appearance and persistence of SARS-CoV-specific antibodies were assessed, with immunoglobulin G detected in 59% of samples collected within 14 days and persisting for 60 to 95 days after the onset of illness.",,"['He, Zhongping', 'Dong, Qingming', 'Zhuang, Hui', 'Song, Shujing', 'Peng, Guoai', 'Luo, Guangxiang', 'Dwyer, Dominic E.']",,,,
,PMC,Evaluation and Validation of an Enzyme-Linked Immunosorbent Assay and an Immunochromatographic Test for Serological Diagnosis of Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1128/CDLI.11.4.699-703.2004,PMC440612,,,"A newly developed severe acute respiratory syndrome (SARS)-specific enzyme-linked immunosorbent assay (ELISA) was further validated to confirm cutoff values and evaluate its diagnostic performance with clinical samples. In parallel, an immunochromatographic test was also evaluated. A total of 227 clinical serum specimens collected from SARS patients were used in the study, together with 385 samples from healthy donors. By use of an immunofluorescent (IF) test as the “gold standard, ” both the ELISA and the immunochromatographic test were able to detect immunoglobulin G antibodies to SARS not only from late-convalescent-stage samples (>21 days from the onset of clinical symptoms), as previously established, but also from early-acute-phase samples (1 to 10 days from onset). The ELISA, using an optical density (OD) of 0.25 as its cutoff value, produced the best sensitivity while maintaining high specificity. It detected SARS-specific antibodies in 58, 70, 75, and 95%, respectively, of the four groups of samples collected from patients 1 to 10 days, 11 to 20 days, 21 to 30 days, and more than 30 days after the onset of clinical symptoms. Similarly, the immunochromatographic test detected SARS-specific antibodies in 55, 68, 81, and 79% of the four groups, respectively. The overall specificities for the ELISA and the rapid test were 99.5 and 97.7%, respectively. Although the positive correlation observed between the ELISA OD values and the IF titers was moderate (r = 0.6915; P < 0.001), the detection rates of both the ELISA and the rapid test were found well in agreement with the IF titers.",,"['Guan, Ming', 'Chan, Kwok Hung', 'Peiris, J. S. Malik', 'Kwan, See Wai', 'Lam, Siu Yan', 'Pang, Chiu Mei', 'Chu, Ka Wing', 'Chan, Kit Man', 'Chen, Hsiao Ying', 'Phuah, Ewe Beng', 'Wong, Caiqin Jane']",,,,
,PMC,"Longitudinal Profile of Immunoglobulin G (IgG), IgM, and IgA Antibodies against the Severe Acute Respiratory Syndrome (SARS) Coronavirus Nucleocapsid Protein in Patients with Pneumonia Due to the SARS Coronavirus",http://dx.doi.org/10.1128/CDLI.11.4.665-668.2004,PMC440610,,,"By using a recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid protein-based enzyme-linked immunosorbent assay (ELISA) and serum specimens serially collected (from day 0 to day 240 after symptom onset) from patients with pneumonia due to SARS-CoV, we analyzed the longitudinal profiles of immunoglobulin G (IgG), IgM, and IgA antibodies against the SARS-CoV nucleocapsid protein in patients with pneumonia due to SARS-CoV. For IgG, the median optical density at 450 nm (OD(450)) turned positive at day 17 and a biphasic response was observed. At day 240, all patients were still positive for anti-nucleocapsid protein IgG antibody. For IgM, the median OD(450) turned positive at day 20.5, peaked at about day 80, and fell to below the baseline level at about day 180. At day 240, 36% of the patients were still positive for anti-nucleocapsid protein IgM antibody. For IgA, the median OD(450) turned positive at day 17, peaked at about day 50, and fell to below the baseline level at about day 180. At day 240, 36% of the patients were still positive for anti-nucleocapsid protein IgA antibody. The time of seroconversion detected by the recombinant SARS-CoV nucleocapsid protein-based ELISA and that detected by indirect immunofluorescence assay were similar. The median times of seroconversion for IgG, IgM, and IgA detected by the indirect immunofluorescence assay were 17 days (17 days by ELISA), 16.5 days (20.5 days by ELISA), and 17.5 days (17 days by ELISA), respectively, after disease onset. One, four, and one of the six patients who died did not produce any IgG, IgM, and IgA antibodies against the nucleocapsid protein of SARS-CoV, respectively, although these antibodies were detected in all six patients by the indirect immunofluorescence assay. Further studies should be performed to see whether SARS-CoV nucleocapsid protein antibody positivity has any prognostic significance.",,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Wong, Beatrice H. L.', 'Chan, Kwok-hung', 'Chu, Chung-ming', 'Tsoi, Hoi-wah', 'Huang, Yi', 'Peiris, J. S. Malik', 'Yuen, Kwok-yung']",,,,
,PMC,Ménage à trois of bacterial and viral pulmonary pathogens delivers coup de grace to the lung,http://dx.doi.org/10.1111/j.1365-2249.2004.02526.x,PMC1809084,,,,,"['HUSSELL, T', 'WILLIAMS, A']",,,,
,PMC,Lymphocyte apoptosis in acute respiratory syncytial virus bronchiolitis,http://dx.doi.org/10.1111/j.1365-2249.2004.02512.x,PMC1809083,,,"Respiratory syncytial virus (RSV) infection may have an effect on the development of T cell memory responses. RSV bronchiolitis in infants is associated with a transient decline in circulating lymphocytes. We hypothesized that the mechanism underlying this lymphopenia is apoptosis. Blood was taken from 32 infants during primary RSV bronchiolitis and three months later. Using flow cytometry, we found that absolute numbers of both CD3+/CD4+ T-helper lymphocytes (P = 0·029) and CD3+/CD8+ cytotoxic lymphocytes (CTL) (P = 0·043) were significantly reduced during acute infection. Up-regulated expression both of Fas (P < 0·001) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor (P < 0·001) was found during acute illness on both CD3+/CD4+ and CD3+/CD8+ lymphocytes, when compared with convalescent samples. Expression of Fas on CD4+ lymphocytes was inversely related to CD4+ number (P = 0·03). Plasma levels of soluble Fas ligand (P = 0·028) and caspase-1 (P = 0·037), determined by enzyme-linked immunosorbent assay, were increased during bronchiolitis. Plasma interleukin-18, a product of caspase-1 activity, was not raised. Taken together, these data suggest that in acute RSV infection, CD4+ helper lymphocytes and CD8+ cytotoxic lymphocytes are primed to undergo apoptosis. This is a mechanism through which lymphopenia may occur and T cell memory may be altered.",,"['ROE, M F E', 'BLOXHAM, D M', 'WHITE, D K', 'ROSS-RUSSELL, R I', 'TASKER, R T C', ""O'DONNELL, D R""]",,,,
,PMC,Murine viral hepatitis involves NK cell depletion associated with virus-induced apoptosis,http://dx.doi.org/10.1111/j.1365-2249.2004.02501.x,PMC1809074,,,"Mouse hepatitis virus type 3 (MHV3), a coronavirus, is an excellent animal model for the study of immunological disorders related to acute and chronic hepatitis. In this study, we have verified if the fulminant hepatitis induced by MHV3 could be related to an impairment of innate immunity. Groups of three C57BL/6 mice were infected with the pathogenic L2-MHV3 or attenuated YAC-MHV3 viruses, and the natural killer (NK) cell populations from liver, spleen and bone marrow were analysed. The percentage of intrahepatic NK1·1(+)T cell receptor (TCR)(−) cells did not increase while NK1·1(+)TCR(inter) cells decreased in both L2-MHV3- and YAC-MHV3-infected mice. Concurrently, splenic and myeloid NK1·1(+) cells decreased in L2-MHV3-infected mice. However, the cytotoxic activity of NK cells increased in liver and decreased in bone marrow from pathogenic L2-MHV3-infected mice while no modification was detected in YAC-MHV3-infected mice. Flow cytometric analysis revealed that both normal and larger splenic or myeloid NK cells decreased more in pathogenic L2-MHV3-infected mice than in attenuated YAC-MHV3-infected mice. In vitro viral infections of interleukin (IL)-15-stimulated lymphoid cells from liver and bone marrow revealed that L2-MHV3 induced higher decreases in cell viability of NK1·1(+) cells than the YAC-MHV3 variant. The NK cell decreases were due to the viral permissivity leading to cytopathic effects characterized by cell rounding, syncytia formation and apoptosis. Larger NK(+) syncytia were observed in L2-MHV3-infected cells than in YAC-MHV3-infected cells. These results suggest that NK cell production is impaired by viral infection favouring fulminant hepatitis.",,"['LEHOUX, M', 'JACQUES, A', 'LUSIGNAN, S', 'LAMONTAGNE, L']",,,,
,PMC,Pathogenesis of Malaria and Clinically Similar Conditions,http://dx.doi.org/10.1128/CMR.17.3.509-539.2004,PMC452556,,,"There is now wide acceptance of the concept that the similarity between many acute infectious diseases, be they viral, bacterial, or parasitic in origin, is caused by the overproduction of inflammatory cytokines initiated when the organism interacts with the innate immune system. This is also true of certain noninfectious states, such as the tissue injury syndromes. This review discusses the historical origins of these ideas, which began with tumor necrosis factor (TNF) and spread from their origins in malaria research to other fields. As well the more established proinflammatory mediators, such as TNF, interleukin-1, and lymphotoxin, the roles of nitric oxide and carbon monoxide, which are chiefly inhibitory, are discussed. The established and potential roles of two more recently recognized contributors, overactivity of the enzyme poly(ADP-ribose) polymerase 1 (PARP-1) and the escape of high-mobility-group box 1 (HMGB1) protein from its normal location into the circulation, are also put in context. The pathogenesis of the disease caused by falciparum malaria is then considered in the light of what has been learned about the roles of these mediators in these other diseases, as well as in malaria itself.",,"['Clark, Ian A.', 'Alleva, Lisa M.', 'Mills, Alison C.', 'Cowden, William B.']",,,,
,PMC,A Consensus Action Agenda for Achieving the National Health Information Infrastructure,http://dx.doi.org/10.1197/jamia.M1616,PMC436084,,,"Background: Improving the safety, quality, and efficiency of health care will require immediate and ubiquitous access to complete patient information and decision support provided through a National Health Information Infrastructure (NHII). Methods: To help define the action steps needed to achieve an NHII, the U.S. Department of Health and Human Services sponsored a national consensus conference in July 2003. Results: Attendees favored a public–private coordination group to guide NHII activities, provide education, share resources, and monitor relevant metrics to mark progress. They identified financial incentives, health information standards, and overcoming a few important legal obstacles as key NHII enablers. Community and regional implementation projects, including consumer access to a personal health record, were seen as necessary to demonstrate comprehensive functional systems that can serve as models for the entire nation. Finally, the participants identified the need for increased funding for research on the impact of health information technology on patient safety and quality of care. Individuals, organizations, and federal agencies are using these consensus recommendations to guide NHII efforts.",,"['Yasnoff, William A.', 'Humphreys, Betsy L.', 'Overhage, J. Marc', 'Detmer, Don E.', 'Brennan, Patricia Flatley', 'Morris, Richard W.', 'Middleton, Blackford', 'Bates, David W.', 'Fanning, John P.']",,,,
,PMC,Discovery of Novel Human and Animal Cells Infected by the Severe Acute Respiratory Syndrome Coronavirus by Replication-Specific Multiplex Reverse Transcription-PCR,http://dx.doi.org/10.1128/JCM.42.7.3196-3206.2004,PMC446305,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) is the causative agent of the recent outbreak of severe acute respiratory syndrome. VeroE6 cells, fetal rhesus monkey kidney cells, and human peripheral blood mononuclear cells were the only cells known to be susceptible to SARS-CoV. We developed a multiplex reverse transcription-PCR assay to analyze the susceptibility of cells derived from a variety of tissues and species to SARS-CoV. Additionally, productive infection was determined by titration of cellular supernatants. Cells derived from three species of monkey were susceptible to SARS-CoV. However, the levels of SARS-CoV produced differed by 4 log(10). Mink lung epithelial cells (Mv1Lu) and R-Mix, a mixed monolayer of human lung-derived cells (A549) and mink lung-derived cells (Mv1Lu), are used by diagnostic laboratories to detect respiratory viruses (e.g., influenza virus); they were also infected with SARS-CoV, indicating that the practices of diagnostic laboratories should be examined to ensure appropriate biosafety precautions. Mv1Lu cells produce little SARS-CoV compared to that produced by VeroE6 cells, which indicates that they are a safer alternative for SARS-CoV diagnostics. Evaluation of cells permissive to other coronaviruses indicated that these cell types are not infected by SARS-CoV, providing additional evidence that SARS-CoV binds an alternative receptor. Analysis of human cells derived from lung, kidney, liver, and intestine led to the discovery that human cell lines were productively infected by SARS-CoV. This study identifies new cell lines that may be used for SARS-CoV diagnostics and/or basic research. Our data and other in vivo studies indicate that SARS-CoV has a wide host range, suggesting that the cellular receptor(s) utilized by SARS-CoV is highly conserved and is expressed by a variety of tissues.",,"['Gillim-Ross, Laura', 'Taylor, Jill', 'Scholl, David R.', 'Ridenour, Jared', 'Masters, Paul S.', 'Wentworth, David E.']",,,,
,PMC,Amplicon Sequencing and Improved Detection of Human Rhinovirus in Respiratory Samples,http://dx.doi.org/10.1128/JCM.42.7.3212-3218.2004,PMC446277,,,"Improved knowledge of the genotypic characteristics of human rhinovirus (HRV) is required, as are nucleic detection assays with the capacity to overcome both the similarities between members of the family Picornaviridae and the wide diversity of different HRV serotypes. The goal of the present study was to investigate the variability and the genotypic diversity of clinical strains circulating in the community. Since most reverse transcription (RT)-PCR assays available cannot differentiate HRV from other members of the family Picornaviridae, we also validated an assay specific for HRV detection. The 5′ noncoding regions of 87 different HRV serotypes and clinical isolates were sequenced. On the basis of sequence analysis and phylogenetic determination, we first confirmed that all clinical isolates were HRV. We then validated a real-time RT-PCR assay that was able not only to detect all HRV serotypes and all clinical isolates tested but also to accurately discriminate between rhinovirus and other viruses from the family Picornaviridae. This assay was negative with isolates of coxsackievirus (types A and B), echovirus, enterovirus, parechovirus, and poliovirus, as well as nonpicornaviruses. Among a series of bronchoalveolar lavage specimens, 4% (7 of 161) were positive by culture, whereas 13% (21 of 161) were positive by RT-PCR. In the present study we showed that to specifically identify HRV in clinical specimens, diagnostic assays need to overcome both the diversities and the similarities of picornaviruses. By sequencing the 5′ noncoding regions of rhinoviruses recovered from clinical specimens, we designed probes that could specifically detect rhinovirus.",,"['Deffernez, Christelle', 'Wunderli, Werner', 'Thomas, Yves', 'Yerly, Sabine', 'Perrin, Luc', 'Kaiser, Laurent']",,,,
,PMC,Detection of Severe Acute Respiratory Syndrome (SARS) Coronavirus Nucleocapsid Protein in SARS Patients by Enzyme-Linked Immunosorbent Assay,http://dx.doi.org/10.1128/JCM.42.7.2884-2889.2004,PMC446266,,,"We report the development of an enzyme-linked immunosorbent assay (ELISA) for the detection of severe acute respiratory syndrome (SARS) coronavirus (CoV) nucleocapsid protein. The assay was carried out with hyperimmune polyclonal nucleocapsid-specific antibodies from guinea pigs and rabbits immunized with recombinant His(6)-tagged SARS CoV nucleocapsid protein. The assay was used for the detection of SARS CoV nucleocapsid protein in nasopharyngeal aspirate, urine, and fecal samples collected from patients with confirmed SARS between days 2 and 33 after the onset of illness. The ELISA was capable of detecting this protein in SARS CoV cell culture lysates at 15 50% tissue culture infective doses/ml but did not produce positive signals when tested with cell culture lysates of human coronaviruses OC43 and 229E. When tested with 120 nasopharyngeal aspirate, 100 urine, and 100 fecal specimens from hospitalized patients without SARS, the assay was shown to have high specificities—96.7, 99, and 96%, respectively. In an evaluation of clinical specimens from SARS patients, 34 (52%) of 66 nasopharyngeal aspirate samples from 50 patients, 5 (5%) of 94 urine samples from 94 patients, and 36 (55%) of 65 fecal samples from 65 patients tested positive for SARS CoV nucleocapsid protein. Nucleocapsid protein could be detected from days 6 to 24 in nasopharyngeal aspirate specimens, from days 11 to 31 in urine specimens, and from days 8 to 32 in fecal specimens after the onset of illness. Moreover, the protein could be detected in 25 (83%) of 30 nasopharyngeal aspirate specimens obtained from days 11 to 15 and in all 7 fecal specimens obtained from days 21 to 32. Since the present ELISA is more convenient and economical than reverse transcription-PCR, it may serve as an alternative tool for the early diagnosis of SARS CoV infection in laboratories with limited resources and expertise and for mass screening for the reservoir of SARS CoV. Further studies on serial clinical specimens should reveal the duration of nucleocapsid protein shedding and may reveal a higher detection rate in SARS patients.",,"['Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Wong, Beatrice H. L.', 'Tsoi, Hoi-Wah', 'Woo, Gibson K. S.', 'Poon, Rosana W. S.', 'Chan, Kwok-Hung', 'Wei, William I.', 'Peiris, J. S. Malik', 'Yuen, Kwok-Yung']",,,,
,PMC,Identification of the Severe Acute Respiratory Syndrome Coronavirus by Simultaneous Multigene DNA Sequencing,http://dx.doi.org/10.1128/JCM.42.7.3291-3294.2004,PMC446234,,,"The recent severe acute respiratory syndrome (SARS) outbreak resulted in calls for an accurate diagnostic test that can be used not only for routine testing but also for generating nucleotide sequences to monitor the epidemic. Although the identity of the SARS coronavirus (SARS-CoV) genome was confirmed by DNA sequencing, it is impractical to sequence the entire 29-kb SARS-CoV genome on a routine basis. Therefore, alternative assay methods such as the enzyme-linked immunosorbent assay and PCR have been pursued for routine testing, primarily to resolve probable cases. We report here a modification of standard DNA sequencing technology for accurate identification of SARS-CoV in routine testing. Instead of requiring the sequencing of the whole SARS-CoV genome, our modification enables the simultaneous sequencing of three regions of the SARS-CoV genome, the spike protein-encoding gene (35 nucleotides), gene M (43 nucleotides), and gene N (45 nucleotides), in a single electropherogram. Comparing these nucleotide sequences to DNA databank entries (National Institutes of Health) conclusively identified them as SARS-CoV sequences.",,"['Vinayagamoorthy, T.', 'Mulatz, Kirk', 'Hodkinson, Roger']",,,,
,PMC,T-Cell Epitopes in Severe Acute Respiratory Syndrome (SARS) Coronavirus Spike Protein Elicit a Specific T-Cell Immune Response in Patients Who Recover from SARS,http://dx.doi.org/10.1128/JVI.78.14.7861.2004,PMC434133,,,,,"['Wang,1,2†, Yue-Dan', 'Sin,2†, Wan-Yee Fion', 'Xu,3†, Guo-Bing', 'Yang,4, Huang-Hao', 'Wong,5, Tin-yau', 'Pang,1, Xue-Wen', 'He,1, Xiao-Yan', 'Zhang,1, Hua-Gang', 'Lee Ng,4, Joice Na', 'Cheng,2, Chak-Sum Samuel', 'Yu,2, Jing', 'Meng,2, Li', 'Yang,3, Rui-Feng', 'Lai,5, Sik-To', 'Guo,4, Zhi-Hong', 'Xie,2*, Yong', 'Chen1*, Wei-Feng']",,,,
,PMC,Expression of the Mouse Hepatitis Virus Receptor by Central Nervous System Microglia,http://dx.doi.org/10.1128/JVI.78.14.7828-7832.2004,PMC434127,,,"Detection of the mouse hepatitis virus receptor within the central nervous system (CNS) has been elusive. Receptor expression on microglia was reduced during acute infection and restored following immune-mediated virus control. Receptor down regulation was independent of neutrophils, NK cells, gamma interferon, or perforin. Infection of mice devoid of distinct inflammatory cells revealed CD4(+) T cells as the major cell type influencing receptor expression by microglia. In addition to demonstrating receptor expression on CNS resident cells, these data suggest that transient receptor down regulation on microglia aids in establishing persistence in the CNS by assisting virus infection of other glial cell types.",,"['Ramakrishna, Chandran', 'Bergmann, Cornelia C.', 'Holmes, Kathryn V.', 'Stohlman, Stephen A.']",,,,
,PMC,National Center for Biotechnology Information Viral Genomes Project,http://dx.doi.org/10.1128/JVI.78.14.7291-7298.2004,PMC434121,,,,,"['Bao, Yiming', 'Federhen, Scott', 'Leipe, Detlef', 'Pham, Vyvy', 'Resenchuk, Sergei', 'Rozanov, Mikhail', 'Tatusov, Roman', 'Tatusova, Tatiana']",,,,
,PMC,Inhibition of Severe Acute Respiratory Syndrome Virus Replication by Small Interfering RNAs in Mammalian Cells,http://dx.doi.org/10.1128/JVI.78.14.7523-7527.2004,PMC434119,,,"Severe acute respiratory syndrome (SARS) is an acute respiratory infectious disease that spread worldwide in early 2003. The cause was determined as a novel coronavirus (CoV), SARS-associated CoV (SARS-CoV), with a single-stranded, plus-sense RNA. To date, no effective specific treatment has been identified. To exploit the possibility of using RNA interference as a therapeutic approach to fight the disease, plasmid-mediated small interfering RNAs (siRNAs) were generated to target the SARS-CoV genome. The expression of siRNAs from two plasmids, which specifically target the viral RNA polymerase, effectively blocked the cytopathic effects of SARS-CoV on Vero cells. These two plasmids also inhibited viral replication as shown by titer assays and by an examination of viral RNA and protein levels. Thus, our results demonstrated the feasibility of developing siRNAs as effective anti-SARS drugs.",,"['Wang, Zhi', 'Ren, Lili', 'Zhao, Xingang', 'Hung, Tao', 'Meng, Anming', 'Wang, Jianwei', 'Chen, Ye-Guang']",,,,
,PMC,"Coronavirus Spike Glycoprotein, Extended at the Carboxy Terminus with Green Fluorescent Protein, Is Assembly Competent",http://dx.doi.org/10.1128/JVI.78.14.7369-7378.2004,PMC434101,,,"Due to the limited ultrastructural information about the coronavirion, little is known about the interactions acting at the interface between nucleocapsid and viral envelope. Knowing that subtle mutations in the carboxy-terminal endodomain of the M protein are already lethal, we have now probed the equivalent domain of the spike (S) protein by extending it terminally with a foreign sequence of 27 kDa: the green fluorescent protein (GFP). When expressed individually in murine cells, the S-GFP chimeric protein induced the formation of fluorescent syncytia, indicating that it was synthesized and folded properly, trimerized, and transported to the plasma membrane, where it exhibited the two key S protein functions, i.e., interaction with virus receptor molecules and membrane fusion. Incorporation into virus-like particles demonstrated the assembly competence of the chimeric spike protein. The wild-type S gene of mouse hepatitis coronavirus (MHV) was subsequently replaced by the chimeric construct through targeted recombination. A viable MHV-SGFP was obtained, infection by which could be visualized by the fluorescence induced. The efficiency of incorporation of the chimeric protein into particles was, however, reduced relative to that in wild-type particles which may explain, at least in part, the reduced infectivity produced by MHV-SGFP infection. We conclude that the incorporation of spikes carrying the large GFP moiety is apparently impaired by geometrical constraints and selected against during the assembly of virions. Probably due to this disadvantage, deletion mutants, having lost the foreign sequences, rapidly evolved and outcompeted the chimeric viruses during virus propagation. The fluorescent MHV-SGFP will now be a convenient tool to study coronaviral cell entry.",,"['Bosch, Berend Jan', 'de Haan, Cornelis A. M.', 'Rottier, Peter J. M.']",,,,
,PMC,The 3′ cis-Acting Genomic Replication Element of the Severe Acute Respiratory Syndrome Coronavirus Can Function in the Murine Coronavirus Genome,http://dx.doi.org/10.1128/JVI.78.14.7846-7851.2004,PMC434098,,,"The 3′ untranslated region (3′ UTR) of the genome of the severe acute respiratory syndrome coronavirus can functionally replace its counterpart in the prototype group 2 coronavirus mouse hepatitis virus (MHV). By contrast, the 3′ UTRs of representative group 1 or group 3 coronaviruses cannot operate as substitutes for the MHV 3′ UTR.",,"['Goebel, Scott J.', 'Taylor, Jill', 'Masters, Paul S.']",,,,
,PMC,Characterization of a Unique Group-Specific Protein (U122) of the Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.78.14.7311-7318.2004,PMC434096,,,"A novel coronavirus (CoV) has been identified as the etiological agent of severe acute respiratory syndrome (SARS). The SARS-CoV genome encodes the characteristic essential CoV replication and structural proteins. Additionally, the genome contains six group-specific open reading frames (ORFs) larger than 50 amino acids, with no known homologues. As with the group-specific genes of the other CoVs, little is known about the SARS-CoV group-specific genes. SARS-CoV ORF7a encodes a putative unique 122-amino-acid protein, designated U122 in this study. The deduced sequence contains a probable cleaved signal sequence and a C-terminal transmembrane helix, indicating that U122 is likely to be a type I membrane protein. The C-terminal tail also contains a typical endoplasmic reticulum (ER) retrieval motif, KRKTE. U122 was expressed in SARS-CoV-infected Vero E6 cells, as it could be detected by Western blot and immunofluorescence analyses. U122 is localized to the perinuclear region of both SARS-CoV-infected and transfected cells and colocalized with ER and intermediate compartment markers. Mutational analyses showed that both the signal peptide sequence and ER retrieval motif were functional.",,"['Fielding, Burtram C.', 'Tan, Yee-Joo', 'Shuo, Shen', 'Tan, Timothy H. P.', 'Ooi, Eng-Eong', 'Lim, Seng Gee', 'Hong, Wanjin', 'Goh, Phuay-Yee']",,,,
,PMC,"Human Coronavirus 229E Nonstructural Protein 13: Characterization of Duplex-Unwinding, Nucleoside Triphosphatase, and RNA 5′-Triphosphatase Activities",http://dx.doi.org/10.1128/JVI.78.14.7833-7838.2004,PMC434081,,,"The human coronavirus 229E (HCoV-229E) replicase gene-encoded nonstructural protein 13 (nsp13) contains an N-terminal zinc-binding domain and a C-terminal superfamily 1 helicase domain. A histidine-tagged form of nsp13, which was expressed in insect cells and purified, is reported to unwind efficiently both partial-duplex RNA and DNA of up to several hundred base pairs. Characterization of the nsp13-associated nucleoside triphosphatase (NTPase) activities revealed that all natural ribonucleotides and nucleotides are substrates of nsp13, with ATP, dATP, and GTP being hydrolyzed most efficiently. Using the NTPase active site, HCoV-229E nsp13 also mediates RNA 5′-triphosphatase activity, which may be involved in the capping of viral RNAs.",,"['Ivanov, Konstantin A.', 'Ziebuhr, John']",,,,
,PMC,"A Novel Severe Acute Respiratory Syndrome Coronavirus Protein, U274, Is Transported to the Cell Surface and Undergoes Endocytosis",http://dx.doi.org/10.1128/JVI.78.13.6723-6734.2004,PMC421683,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) genome contains open reading frames (ORFs) that encode for several genes that are homologous to proteins found in all known coronaviruses. These are the replicase gene 1a/1b and the four structural proteins, nucleocapsid (N), spike (S), membrane (M), and envelope (E), and these proteins are expected to be essential for the replication of the virus. In addition, this genome also contains nine other potential ORFs varying in length from 39 to 274 amino acids. The largest among these is the first ORF of the second longest subgenomic RNA, and this protein (termed U274 in the present study) consists of 274 amino acids and contains three putative transmembrane domains. Using antibody specific for the C terminus of U274, we show U274 to be expressed in SARS-CoV-infected Vero E6 cells and, in addition to the full-length protein, two other processed forms were also detected. By indirect immunofluorescence, U274 was localized to the perinuclear region, as well as to the plasma membrane, in both transfected and infected cells. Using an N terminus myc-tagged U274, the topology of U274 and its expression on the cell surface were confirmed. Deletion of a cytoplasmic domain of U274, which contains Yxxφ and diacidic motifs, abolished its transport to the cell surface. In addition, U274 expressed on the cell surface can internalize antibodies from the culture medium into the cells. Coimmunoprecipitation experiments also showed that U274 could interact specifically with the M, E, and S structural proteins, as well as with U122, another protein that is unique to SARS-CoV.",,"['Tan, Yee-Joo', 'Teng, Eileen', 'Shen, Shuo', 'Tan, Timothy H. P.', 'Goh, Phuay-Yee', 'Fielding, Burtram C.', 'Ooi, Eng-Eong', 'Tan, Hwee-Cheng', 'Gee Lim, Seng', 'Hong, Wanjin']",,,,
,PMC,Identification of an Antigenic Determinant on the S2 Domain of the Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Capable of Inducing Neutralizing Antibodies,http://dx.doi.org/10.1128/JVI.78.13.6938-6945.2004,PMC421668,,,"Severe acute respiratory syndrome (SARS) is a life-threatening disease caused by a newly identified coronavirus (CoV), SARS-CoV. The spike (S) glycoprotein of CoV is the major structural protein responsible for induction of host immune response and virus neutralization by antibodies. Hence, knowledge of neutralization determinants on the S protein is helpful for designing protective vaccines. To analyze the antigenic structure of the SARS-CoV S2 domain, the carboxyl-terminal half of the S protein, we first used sera from convalescent SARS patients to test the antigenicity of 12 overlapping fragments spanning the entire S2 and identified two antigenic determinants (Leu 803 to Ala 828 and Pro 1061 to Ser 1093). To determine whether neutralizing antibodies can be elicited by these two determinants, we immunized animals and found that both of them could induce the S2-specific antisera. In some animals, however, only one determinant (Leu 803 to Ala 828) was able to induce the antisera with the binding ability to the native S protein and the neutralizing activity to the SARS-CoV pseudovirus. This determinant is highly conserved across different SARS-CoV isolates. Identification of a conserved antigenic determinant on the S2 domain of the SARS-CoV S protein, which has the potential for inducing neutralizing antibodies, has implications in the development of effective vaccines against SARS-CoV.",,"['Zhang, Hong', 'Wang, Guangwen', 'Li, Jian', 'Nie, Yuchun', 'Shi, Xuanling', 'Lian, Gewei', 'Wang, Wei', 'Yin, Xiaolei', 'Zhao, Yang', 'Qu, Xiuxia', 'Ding, Mingxiao', 'Deng, Hongkui']",,,,
,PMC,An Exposed Domain in the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Induces Neutralizing Antibodies,http://dx.doi.org/10.1128/JVI.78.13.7217-7226.2004,PMC421657,,,"Exposed epitopes of the spike protein may be recognized by neutralizing antibodies against severe acute respiratory syndrome (SARS) coronavirus (CoV). A protein fragment (S-II) containing predicted epitopes of the spike protein was expressed in Escherichia coli. The properly refolded protein fragment specifically bound to the surface of Vero cells. Monoclonal antibodies raised against this fragment recognized the native spike protein of SARS CoV in both monomeric and trimeric forms. These monoclonal antibodies were capable of blocking S-II attachment to Vero cells and exhibited in vitro antiviral activity. These neutralizing antibodies mapped to epitopes in two peptides, each comprising 20 amino acids. Thus, this region of the spike protein might be a target for generation of therapeutic neutralizing antibodies against SARS CoV and for vaccine development to elicit protective humoral immunity.",,"['Zhou, Tong', 'Wang, Hong', 'Luo, Danlin', 'Rowe, Thomas', 'Wang, Zheng', 'Hogan, Robert J.', 'Qiu, Shihong', 'Bunzel, Robert J.', 'Huang, Guoqiang', 'Mishra, Vinod', 'Voss, Thomas G.', 'Kimberly, Robert', 'Luo, Ming']",,,,
,PMC,CVTree: a phylogenetic tree reconstruction tool based on whole genomes,http://dx.doi.org/10.1093/nar/gkh362,PMC441500,,,"Composition Vector Tree (CVTree) implements a systematic method of inferring evolutionary relatedness of microbial organisms from the oligopeptide content of their complete proteomes (http://cvtree.cbi.pku.edu.cn). Since the first bacterial genomes were sequenced in 1995 there have been several attempts to infer prokaryote phylogeny from complete genomes. Most of them depend on sequence alignment directly or indirectly and, in some cases, need fine-tuning and adjustment. The composition vector method circumvents the ambiguity of choosing the genes for phylogenetic reconstruction and avoids the necessity of aligning sequences of essentially different length and gene content. This new method does not contain ‘free’ parameter and ‘fine-tuning’. A bootstrap test for a phylogenetic tree of 139 organisms has shown the stability of the branchings, which support the small subunit ribosomal RNA (SSU rRNA) tree of life in its overall structure and in many details. It may provide a quick reference in prokaryote phylogenetics whenever the proteome of an organism is available, a situation that will become commonplace in the near future.",,"['Qi, Ji', 'Luo, Hong', 'Hao, Bailin']",,,,
,PMC,Severe acute respiratory syndrome (SARS): epidemiology and clinical features,http://dx.doi.org/10.1136/pgmj.2004.020263,PMC1743054,,,"Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease with a significant morbidity and mortality. The major clinical features include persistent fever, chills/rigor, myalgia, malaise, dry cough, headache, and dyspnoea. Older subjects may present without the typical febrile response. Common laboratory features include lymphopenia, thrombocytopenia, raised alanine transaminases, lactate dehydrogenase, and creatine kinase. The constellation of compatible clinical and laboratory findings, together with certain characteristic radiological features and lack of clinical response to broad spectrum antibiotics, should arouse suspicion of SARS. Measurement of serum RNA by real time reverse transcriptase-polymerase chain reaction technique has a detection rate of 75%–80% in the first week of the illness.",,"['Hui, D', 'Chan, M', 'Wu, A', 'Ng, P']",,,,
,PMC,Small molecules targeting severe acute respiratory syndrome human coronavirus,http://dx.doi.org/10.1073/pnas.0403596101,PMC454157,,,"Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel human coronavirus. Currently, no effective antiviral agents exist against this type of virus. A cell-based assay, with SARS virus and Vero E6 cells, was developed to screen existing drugs, natural products, and synthetic compounds to identify effective anti-SARS agents. Of >10,000 agents tested, ≈50 compounds were found active at 10 μM; among these compounds, two are existing drugs (Reserpine 13 and Aescin 5) and several are in clinical development. These 50 active compounds were tested again, and compounds 2–6, 10, and 13 showed active at 3 μM. The 50% inhibitory concentrations for the inhibition of viral replication (EC(50)) and host growth (CC(50)) were then measured and the selectivity index (SI = CC(50)/EC(50)) was determined. The EC(50), based on ELISA, and SI for Reserpine, Aescim, and Valinomycin are 3.4 μM (SI = 7.3), 6.0 μM (SI = 2.5), and 0.85 μM (SI = 80), respectively. Additional studies were carried out to further understand the mode of action of some active compounds, including ELISA, Western blot analysis, immunofluorescence and flow cytometry assays, and inhibition against the 3CL protease and viral entry. Of particular interest are the two anti-HIV agents, one as an entry blocker and the other as a 3CL protease inhibitor (K(i) = 0.6 μM).",,"['Wu, Chung-Yi', 'Jan, Jia-Tsrong', 'Ma, Shiou-Hwa', 'Kuo, Chih-Jung', 'Juan, Hsueh-Fen', 'Cheng, Yih-Shyun E.', 'Hsu, Hsien-Hua', 'Huang, Hsuan-Cheng', 'Wu, Douglass', 'Brik, Ashraf', 'Liang, Fu-Sen', 'Liu, Rai-Shung', 'Fang, Jim-Min', 'Chen, Shui-Tein', 'Liang, Po-Huang', 'Wong, Chi-Huey']",,,,
,PMC,Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity,http://dx.doi.org/10.1073/pnas.0403492101,PMC470755,,,"We investigated the contributions of the structural proteins of severe acute respiratory syndrome (SARS) coronavirus (CoV) to protective immunity by expressing them individually and in combinations from a recombinant parainfluenza virus (PIV) type 3 vector called BHPIV3. This vector provided direct immunization of the respiratory tract, the major site of SARS transmission, replication, and disease. The BHPIV3/SARS recombinants were evaluated for immunogenicity and protective efficacy in hamsters, which support a high level of pulmonary SARS-CoV replication. A single intranasal administration of BHPIV3 expressing the SARS-CoV spike protein (S) induced a high titer of SARS-CoV-neutralizing serum antibodies, only 2-fold less than that induced by SARS-CoV infection. The expression of S with the two other putative virion envelope proteins, the matrix M and small envelope E proteins, did not augment the neutralizing antibody response. In absence of S, expression of M and E or the nucleocapsid protein N did not induce a detectable serum SARS-CoV-neutralizing antibody response. Immunization with BHPIV3 expressing S provided complete protection against SARS-CoV challenge in the lower respiratory tract and partial protection in the upper respiratory tract. This was augmented slightly by coexpression with M and E. Expression of M, E, or N in the absence of S did not confer detectable protection. These results identify S among the structural proteins as the only significant SARS-CoV neutralization antigen and protective antigen and show that a single mucosal immunization is highly protective in an experimental animal that supports efficient replication of SARS-CoV.",,"['Buchholz, Ursula J.', 'Bukreyev, Alexander', 'Yang, Lijuan', 'Lamirande, Elaine W.', 'Murphy, Brian R.', 'Subbarao, Kanta', 'Collins, Peter L.']",,,,
,PMC,Canadian hospitals fight a rise in infections with Clostridium difficile,,PMC428509,,,,,"Spurgeon, David",,,,
,PMC,Tackling the next influenza pandemic: “Ring” prophylaxis of close contacts with antivirals may be an effective strategy,,PMC421767,,,,,"['Balicer, Ran D', 'Huerta, Michael', 'Grotto, Itamar']",,,,
,PMC,Using conservation of pattern to estimate spatial parameters from a single snapshot,http://dx.doi.org/10.1073/pnas.0400335101,PMC428489,,,"Rapid reaction in the face of an epidemic is a key element in effective and efficient control; this is especially important when the disease has severe public health or economic consequences. Determining an appropriate level of response requires rapid estimation of the rate of spread of infection from limited disease distribution data. Generally, the techniques used to estimate such spatial parameters require detailed spatial data at multiple time points; such data are often time-consuming and expensive to collect. Here we present an alternative approach that is computationally efficient and only requires spatial data from a single time point, hence saving valuable time at the start of the epidemic. By assuming that fundamental spatial statistics are near equilibrium, parameters can be estimated by minimizing the expected rate of change of these statistics, hence conserving the general spatial pattern. Although applicable to both ecological and epidemiological data, here we focus on disease data from computer simulations and real epidemics to show that this method produces reliable results that could be used in practical situations.",,"['Keeling, Matt J.', 'Brooks, Stephen P.', 'Gilligan, Christopher A.']",,,,
,PMC,New guidelines aim to improve management of COPD,,PMC420316,,,,,"Mayor, Susan",,,,
,PMC,Experimental Human Metapneumovirus Infection of Cynomolgus Macaques (Macaca fascicularis) Results in Virus Replication in Ciliated Epithelial Cells and Pneumocytes with Associated Lesions throughout the Respiratory Tract,,PMC1615765,,,"A substantial proportion of hitherto unexplained respiratory tract illnesses is associated with human metapneumovirus (hMPV) infection. This virus also was found in patients with severe acute respiratory syndrome (SARS). To determine the dynamics and associated lesions of hMPV infection, six cynomolgus macaques (Macaca fascicularis) were inoculated with hMPV and examined by pathological and virological assays. They were euthanized at 5 (n = 2) or 9 (n = 2) days post-infection (dpi), or monitored until 14 dpi (n = 2). Viral excretion peaked at 4 dpi and decreased to zero by 10 dpi. Viral replication was restricted to the respiratory tract and associated with minimal to mild, multi-focal erosive and inflammatory changes in conducting airways, and increased numbers of macrophages in alveoli. Viral expression was seen mainly at the apical surface of ciliated epithelial cells throughout the respiratory tract, and less frequently in type 1 pneumocytes and alveolar macrophages. Both cell tropism and respiratory lesions were distinct from those of SARS-associated coronavirus infection, excluding hMPV as the primary cause of SARS. This study demonstrates that hMPV is a respiratory pathogen and indicates that viral replication is short-lived, polarized to the apical surface, and occurs primarily in ciliated respiratory epithelial cells.",,"['Kuiken, Thijs', 'van den Hoogen, Bernadette G.', 'van Riel, Debby A.J.', 'Laman, Jon D.', 'van Amerongen, Geert', 'Sprong, Leo', 'Fouchier, Ron A.M.', 'Osterhaus, Albert D.M.E.']",,,,
,PMC,Uncertain Benefit: The Public Policy of Approving Smallpox Vaccine Research,,PMC1448369,,,"Without an accurate assessment of the prospect of bioterrorist attack, it is especially challenging to evaluate the protocols for testing smallpox vaccines in the pediatric population. Usual regulatory mechanisms cannot shepherd research protocols with benefits that can only be characterized as “uncertain” in the face of more than minimal risk. When a protocol is placed in a government forum for analysis, the public has a unique opportunity to debate the balancing of research risks and benefits on behalf of children who are unable to assent to research themselves, as well as to express views about vaccination policy broadly. This model for review of pediatric research that may be without benefit will be especially important as challenging studies of various vaccines against a range of infectious properties, such as anthrax and severe acute respiratory syndrome (SARS), emerge.",,"Quigley, Rosemary B",,,,
,PMC,Severe acute respiratory syndrome in Singapore,http://dx.doi.org/10.1136/adc.2003.039420,PMC1719957,,,"Aims: To describe the epidemiological and clinical features of paediatric severe acute respiratory syndrome (SARS) in Singapore. Methods: The following data were retrospectively collected from the case records of all 71 patients (aged 7 months to 14 years) admitted from 23 March to 22 May 2003 to the SARS paediatric unit: patient demographics, contact history, clinical features, physiological parameters, investigations, treatment, and outcome. Using WHO criteria there were seven probable (P), 23 suspect (S), and 41 observe (O) cases. Results: Compared to the O cases P patients had a longer mean duration of fever (3.66 (SD 2.3) v 8.57 (SD 2.44) days), lower mean thrombocytopenia (248.3 (SD 82.7) v 173.7 (SD 49.0)x10(9)/l), leucopenia (8.19 (SD 4.45) v 3.06 (SD 1.02)x10(9)/l), lymphopenia (2.79 (SD 1.97) v 1.44 (SD 0.75)x10(9)/l), and neutropenia (4.48 (SD 2.88) v 1.24 (SD 0.43)x10(9)/l). Chest auscultation was abnormal in 71% of P patients, with mild crepitations detected. All had abnormal chest radiographs versus 39% of S cases, and 27% of O cases. Conclusions: There are no distinguishing clinical features of paediatric SARS. The diagnosis is suggested by the paucity of clinical signs with an abnormal chest radiograph, and laboratory evidence of leucopenia, lymphopenia, and thrombocytopenia.",,"['Puthucheary, J', 'Lim, D', 'Chan, I', 'Chay, O', 'Choo, P']",,,,
,PMC,"SARS outbreak over, but concerns for lab safety remain.",,PMC2622862,,,,,"Fleck, Fiona",,,,
,PMC,In Beijing during the SARS outbreak.,,PMC2214625,,,,,"Borwein, Sarah",,,,
,PMC,Author index,http://dx.doi.org/10.1111/j.1365-2249.2004.02516.x,PMC1809049,,,,,,,,,
,PMC,Subject index,http://dx.doi.org/10.1111/j.1365-2249.2004.02517.x,PMC1809043,,,,,,,,,
,PMC,Overcoming resistance,http://dx.doi.org/10.1038/sj.embor.7400181,PMC1299089,,,"Rather than waiting for new drugs, surveillance and education might be more efficient strategies to combat rising antimicrobial resistance",,"Hadley, Caroline",,,,
,PMC,"An epidemic of gastroenteritis and mild necrotizing enterocolitis in two neonatal units of a University Hospital in Rome, Italy.",,PMC2870125,,,"In the summer of 1999 a cluster of 18 cases of necrotizing enterocolitis (NEC) occurred in a University Hospital in Rome, Italy. The cases presented with mild clinical and radiological signs, and none died. Seventy-two per cent had a birth weight of > 2500 g, 66.7% had a gestational age of > 37 weeks, 30% presented with respiratory diseases and/or hypoglycaemia. All cases occurred within 10 days of birth and between 5 and 7 days after two clusters of diarrhoea (14 cases). The NEC outbreak had two phases; most cases in the first phase occurred in the at-risk unit, whereas those in the second phase occurred in the full-term unit. In the multivariate analysis, invasive therapeutic procedures, pathological conditions and formula feeding were associated with NEC. Although no predominant common bacteria were isolated, we suggest an infective origin of this outbreak.",,"['Faustini, A.', 'Forastiere, F.', 'Giorgi Rossi, P.', 'Perucci, C. A.']",,,,
,PMC,Hospitalized patients with bacterial infections: a potential focus of SARS transmission during an outbreak.,,PMC2870119,,,,,"['Wilder-Smith, A.', 'Green, J. A.', 'Paton, N. I.']",,,,
,PMC,Sensitive and Specific Monoclonal Antibody-Based Capture Enzyme Immunoassay for Detection of Nucleocapsid Antigen in Sera from Patients with Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1128/JCM.42.6.2629-2635.2004,PMC427886,,,"A rapid antigen test for the diagnosis of severe acute respiratory syndrome (SARS) is essential for control of this disease at the point of management. The nucleocapsid (N) protein of SARS-associated coronavirus (SARS-CoV) is abundantly expressed in infected-cell culture filtrate as demonstrable by Western blotting using convalescent-phase sera from patients with SARS. We used monoclonal antibodies specifically directed against N protein to establish a sensitive antigen capture sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of SARS-CoV. The assay employed a mixture of three monoclonal antibodies for capture and rabbit polyclonal antibodies for detection of serum antigen in 32 cases of clinically probable SARS as defined by the World Health Organization during the epidemic in Guangzhou, China. Recombinant N protein was used as a standard to establish a detection sensitivity of approximated 50 pg/ml. The linear range of detection in clinical specimens was from 100 pg/ml to 3.2 ng/ml. Using a panel of sera collected at different points in time, the amount of circulating N antigen was found to peak 6 to 10 days after the onset of symptoms. The sensitivity of the assay was 84.6% in 13 serologically confirmed SARS patients with blood taken during the first 10 days after the onset of symptoms (11 of 13). The specificity of the assay was 98.5% in 1,272 healthy individuals (1,253 of 1,272). There was no cross-reaction with other human and animal coronaviruses in this assay. In conclusion, a sensitive and quantitative antigen capture ELISA was established for the early diagnosis and disease monitoring of SARS-CoV infection.",,"['Che, Xiao-yan', 'Qiu, Li-wen', 'Pan, Yu-xian', 'Wen, Kun', 'Hao, Wei', 'Zhang, Li-ya', 'Wang, Ya-di', 'Liao, Zhi-yong', 'Hua, Xu', 'Cheng, Vincent C. C.', 'Yuen, Kwok-yung']",,,,
,PMC,Response of the Clinical Microbiology Laboratory to Emerging (New) and Reemerging Infectious Diseases,http://dx.doi.org/10.1128/JCM.42.6.2359-2365.2004,PMC427820,,,,,"['Cockerill, Franklin R.', 'Smith, Thomas F.']",,,,
,PMC,High-Efficiency Detection of Severe Acute Respiratory Syndrome Virus Genetic Material,http://dx.doi.org/10.1128/JCM.42.6.2771-2773.2004,PMC427811,,,A Taqman amplicon targeting the nucleocapsid gene of severe acute respiratory syndrome coronavirus (SARS-CoV) is 5 log(10) times more sensitive for SARS-CoV target RNA extracted from infected cells and 2.79 log(10) times more sensitive for RNA extracted from patient material of the index case in Frankfurt than an amplicon targeting the polymerase gene.,,"['Weidmann, Manfred', 'Zanotto, Paolo M. D. A.', 'Weber, Friedemann', 'Spiegel, Martin', 'Brodt, Hans Rheinhard', 'Hufert, Frank T.']",,,,
,PMC,Requirements for Brome Mosaic Virus Subgenomic RNA Synthesis In Vivo and Replicase-Core Promoter Interactions In Vitro,http://dx.doi.org/10.1128/JVI.78.12.6091-6101.2004,PMC416551,,,"Based solely on in vitro results, two contrasting models have been proposed for the recognition of the brome mosaic virus (BMV) subgenomic core promoter by the replicase. The first posits that the replicase recognizes at least four key nucleotides in the core promoter, followed by an induced fit, wherein some of the nucleotides base pair prior to the initiation of RNA synthesis (S. Adkins and C. C. Kao, Virology 252:1-8, 1998). The second model posits that a short RNA hairpin in the core promoter serves as a landing pad for the replicase and that at least some of the key nucleotides help form a stable hairpin (P. C. J. Haasnoot, F. Brederode, R. C. L. Olsthoorn, and J. Bol, RNA 6:708-716, 2000; P. C. J. Haasnoot, R. C. L. Olsthoorn, and J. Bol, RNA 8:110-122, 2002). We used transfected barley protoplasts to examine the recognition of the subgenomic core promoter by the BMV replicase. Key nucleotides required for subgenomic initiation in vitro were found to be important for RNA4 levels in protoplasts. In addition, additional residues not required in vitro and the formation of an RNA hairpin within the core promoter were correlated with wild-type RNA4 levels in cells. Using a template competition assay, the core promoter of ca. 20 nucleotides was found to be sufficient for replicase binding. Mutations of the key residues in the core promoter reduced replicase binding, but deletions that disrupt the predicted base pairing in the proposed stem retained binding at wild-type levels. Together, these results indicate that key nucleotides in the BMV subgenomic core promoter direct replicase recognition but that the formation of a stem-loop is required at a step after binding. Additional functional characterization of the subgenomic core promoter was performed. A portion of the promoter for BMV minus-strand RNA synthesis could substitute for the subgenomic core promoter in transfected cells. The comparable sequence from Cowpea Chlorotic Mottle Virus (CCMV) could also substitute for the BMV subgenomic core promoter. However, nucleotides in the CCMV core required for RNA synthesis are not identical to those in BMV, suggesting that the subgenomic core promoter can induce the BMV replicase in interactions needed for subgenomic RNA transcription in vivo.",,"['Sivakumaran, K.', 'Choi, Seung-Kook', 'Hema, Masarapu', 'Kao, C. Cheng']",,,,
,PMC,S Protein of Severe Acute Respiratory Syndrome-Associated Coronavirus Mediates Entry into Hepatoma Cell Lines and Is Targeted by Neutralizing Antibodies in Infected Patients,http://dx.doi.org/10.1128/JVI.78.12.6134-6142.2004,PMC416513,,,"The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes severe pneumonia with a fatal outcome in approximately 10% of patients. SARS-CoV is not closely related to other coronaviruses but shares a similar genome organization. Entry of coronaviruses into target cells is mediated by the viral S protein. We functionally analyzed SARS-CoV S using pseudotyped lentiviral particles (pseudotypes). The SARS-CoV S protein was found to be expressed at the cell surface upon transient transfection. Coexpression of SARS-CoV S with human immunodeficiency virus-based reporter constructs yielded viruses that were infectious for a range of cell lines. Most notably, viral pseudotypes harboring SARS-CoV S infected hepatoma cell lines but not T- and B-cell lines. Infection of the hepatoma cell line Huh-7 was also observed with replication-competent SARS-CoV, indicating that hepatocytes might be targeted by SARS-CoV in vivo. Inhibition of vacuolar acidification impaired infection by SARS-CoV S-bearing pseudotypes, indicating that S-mediated entry requires low pH. Finally, infection by SARS-CoV S pseudotypes but not by vesicular stomatitis virus G pseudotypes was efficiently inhibited by a rabbit serum raised against SARS-CoV particles and by sera from SARS patients, demonstrating that SARS-CoV S is a target for neutralizing antibodies and that such antibodies are generated in SARS-CoV-infected patients. Our results show that viral pseudotyping can be employed for the analysis of SARS-CoV S function. Moreover, we provide evidence that SARS-CoV infection might not be limited to lung tissue and can be inhibited by the humoral immune response in infected patients.",,"['Hofmann, Heike', 'Hattermann, Kim', 'Marzi, Andrea', 'Gramberg, Thomas', 'Geier, Martina', 'Krumbiegel, Mandy', 'Kuate, Seraphin', 'Überla, Klaus', 'Niedrig, Matthias', 'Pöhlmann, Stefan']",,,,
,PMC,Intracellular Targeting Signals Contribute to Localization of Coronavirus Spike Proteins near the Virus Assembly Site,http://dx.doi.org/10.1128/JVI.78.11.5913-5922.2004,PMC415842,,,"Coronavirus budding at the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) requires accumulation of the viral envelope proteins at this point in the secretory pathway. Here we demonstrate that the spike (S) protein from the group 3 coronavirus infectious bronchitis virus (IBV) contains a canonical dilysine endoplasmic reticulum retrieval signal (-KKXX-COOH) in its cytoplasmic tail. This signal can retain a chimeric reporter protein in the ERGIC and when mutated allows transport of the full-length S protein as well as the chimera to the plasma membrane. Interestingly, the IBV S protein also contains a tyrosine-based endocytosis signal in its cytoplasmic tail, suggesting that any S protein that escapes the ERGIC will be rapidly endocytosed when it reaches the plasma membrane. We also identified a novel dibasic motif (-KXHXX-COOH) in the cytoplasmic tails of S proteins from group 1 coronaviruses and from the newly identified coronavirus implicated in severe acute respiratory syndrome. This dibasic motif also retained a reporter protein in the ERGIC, similar to the dilysine motif in IBV S. The cytoplasmic tails of S proteins from group 2 coronaviruses lack an intracellular localization signal. The inherent differences in S-protein trafficking could point to interesting variations in pathogenesis of coronaviruses, since increased levels of surface S protein could promote syncytium formation and direct cell-to-cell spread of the infection.",,"['Lontok, Erik', 'Corse, Emily', 'Machamer, Carolyn E.']",,,,
,PMC,pH-Dependent Entry of Severe Acute Respiratory Syndrome Coronavirus Is Mediated by the Spike Glycoprotein and Enhanced by Dendritic Cell Transfer through DC-SIGN,http://dx.doi.org/10.1128/JVI.78.11.5642-5650.2004,PMC415834,,,"The severe acute respiratory syndrome coronavirus (SARS-CoV) synthesizes several putative viral envelope proteins, including the spike (S), membrane (M), and small envelope (E) glycoproteins. Although these proteins likely are essential for viral replication, their specific roles in SARS-CoV entry have not been defined. In this report, we show that the SARS-CoV S glycoprotein mediates viral entry through pH-dependent endocytosis. Further, we define its cellular tropism and demonstrate that virus transmission occurs through cell-mediated transfer by dendritic cells. The S glycoprotein was used successfully to pseudotype replication-defective retroviral and lentiviral vectors that readily infected Vero cells as well as primary pulmonary and renal epithelial cells from human, nonhuman primate, and, to a lesser extent, feline species. The tropism of this reporter virus was similar to that of wild-type, replication-competent SARS-CoV, and binding of purified S to susceptible target cells was demonstrated by flow cytometry. Although myeloid dendritic cells were able to interact with S and to bind virus, these cells could not be infected by SARS-CoV. However, these cells were able to transfer the virus to susceptible target cells through a synapse-like structure. Both cell-mediated infection and direct infection were inhibited by anti-S antisera, indicating that strategies directed toward this gene product are likely to confer a therapeutic benefit for antiviral drugs or the development of a SARS vaccine.",,"['Yang, Zhi-Yong', 'Huang, Yue', 'Ganesh, Lakshmanan', 'Leung, Kwanyee', 'Kong, Wing-Pui', 'Schwartz, Owen', 'Subbarao, Kanta', 'Nabel, Gary J.']",,,,
,PMC,Multiple Enzymatic Activities Associated with Severe Acute Respiratory Syndrome Coronavirus Helicase,http://dx.doi.org/10.1128/JVI.78.11.5619-5632.2004,PMC415832,,,"Severe acute respiratory syndrome coronavirus (SARS-CoV), a newly identified group 2 coronavirus, is the causative agent of severe acute respiratory syndrome, a life-threatening form of pneumonia in humans. Coronavirus replication and transcription are highly specialized processes of cytoplasmic RNA synthesis that localize to virus-induced membrane structures and were recently proposed to involve a complex enzymatic machinery that, besides RNA-dependent RNA polymerase, helicase, and protease activities, also involves a series of RNA-processing enzymes that are not found in most other RNA virus families. Here, we characterized the enzymatic activities of a recombinant form of the SARS-CoV helicase (nonstructural protein [nsp] 13), a superfamily 1 helicase with an N-terminal zinc-binding domain. We report that nsp13 has both RNA and DNA duplex-unwinding activities. SARS-CoV nsp13 unwinds its substrates in a 5′-to-3′ direction and features a remarkable processivity, allowing efficient strand separation of extended regions of double-stranded RNA and DNA. Characterization of the nsp13-associated (deoxy)nucleoside triphosphatase ([dNTPase) activities revealed that all natural nucleotides and deoxynucleotides are substrates of nsp13, with ATP, dATP, and GTP being hydrolyzed slightly more efficiently than other nucleotides. Furthermore, we established an RNA 5′-triphosphatase activity for the SARS-CoV nsp13 helicase which may be involved in the formation of the 5′ cap structure of viral RNAs. The data suggest that the (d)NTPase and RNA 5′-triphosphatase activities of nsp13 have a common active site. Finally, we established that, in SARS-CoV-infected Vero E6 cells, nsp13 localizes to membranes that appear to be derived from the endoplasmic reticulum and are the likely site of SARS-CoV RNA synthesis.",,"['Ivanov, Konstantin A.', 'Thiel, Volker', 'Dobbe, Jessika C.', 'van der Meer, Yvonne', 'Snijder, Eric J.', 'Ziebuhr, John']",,,,
,PMC,Murine Coronavirus Replication Induces Cell Cycle Arrest in G(0)/G(1) Phase,http://dx.doi.org/10.1128/JVI.78.11.5658-5669.2004,PMC415820,,,"Mouse hepatitis virus (MHV) replication in actively growing DBT and 17Cl-1 cells resulted in the inhibition of host cellular DNA synthesis and the accumulation of infected cells in the G(0)/G(1) phase of the cell cycle. UV-irradiated MHV failed to inhibit host cellular DNA synthesis. MHV infection in quiescent 17Cl-1 cells that had been synchronized in the G(0) phase by serum deprivation prevented infected cells from entering the S phase after serum stimulation. MHV replication inhibited hyperphosphorylation of the retinoblastoma protein (pRb), the event that is necessary for cell cycle progression through late G(1) and into the S phase. While the amounts of the cellular cyclin-dependent kinase (Cdk) inhibitors p21(Cip1), p27(Kip1), and p16(INK4a) did not change in infected cells, MHV infection in asynchronous cultures induced a clear reduction in the amounts of Cdk4 and G(1) cyclins (cyclins D1, D2, D3, and E) in both DBT and 17Cl-1 cells and a reduction in Cdk6 levels in 17Cl-1 cells. Infection also resulted in a decrease in Cdk2 activity in both cell lines. MHV infection in quiescent 17Cl-1 cells prevented normal increases in Cdk4, Cdk6, cyclin D1, and cyclin D3 levels after serum stimulation. The amounts of cyclin D2 and cyclin E were not increased significantly after serum stimulation in mock-infected cells, whereas they were decreased in MHV-infected cells, suggesting the possibility that MHV infection may induce cyclin D2 and cyclin E degradation. Our data suggested that a reduction in the amounts of G(1) cyclin-Cdk complexes in MHV-infected cells led to a reduction in Cdk activities and insufficient hyperphosphorylation of pRb, resulting in inhibition of the cell cycle in the G(0)/G(1) phase.",,"['Chen, Chun-Jen', 'Makino, Shinji']",,,,
,PMC,T-Cell Epitopes in Severe Acute Respiratory Syndrome (SARS) Coronavirus Spike Protein Elicit a Specific T-Cell Immune Response in Patients Who Recover from SARS,http://dx.doi.org/10.1128/JVI.78.11.5612-5618.2004,PMC415819,,,"The immunogenicity of HLA-A2-restricted T-cell epitopes in the S protein of the Severe acute respiratory syndrome coronavirus (SARS-CoV) and of human coronavirus strain 229e (HCoV-229e) was analyzed for the elicitation of a T-cell immune response in donors who had fully recovered from SARS-CoV infection. We employed online database analysis to compare the differences in the amino acid sequences of the homologous T epitopes of HCoV-229e and SARS-CoV. The identified T-cell epitope peptides were synthesized, and their binding affinities for HLA-A2 were validated and compared in the T2 cell system. The immunogenicity of all these peptides was assessed by using T cells obtained from donors who had fully recovered from SARS-CoV infection and from healthy donors with no history of SARS-CoV infection. HLA-A2 typing by indirect immunofluorescent antibody staining showed that 51.6% of SARS-CoV-infected patients were HLA-A2 positive. Online database analysis and the T2 cell binding test disclosed that the number of HLA-A2-restricted immunogenic epitopes of the S protein of SARS-CoV was decreased or even lost in comparison with the homologous sequences of the S protein of HCoV-229e. Among the peptides used in the study, the affinity of peptides from HCoV-229e (H77 and H881) and peptides from SARS-CoV (S978 and S1203) for binding to HLA-A2 was higher than that of other sequences. The gamma interferon (IFN-γ) release Elispot assay revealed that only SARS-CoV-specific peptides S1203 and S978 induced a high frequency of IFN-γ-secreting T-cell response in HLA-A2(+) donors who had fully recovered from SARS-CoV infection; such a T-cell epitope-specific response was not observed in HLA-A2(+) healthy donors or in HLA-A2(−) donors who had been infected with SARS-CoV after full recovery. Thus, T-cell epitopes S1203 and S978 are immunogenic and elicit an overt specific T-cell response in HLA-A2(+) SARS-CoV-infected patients.",,"['Wang, Yue-Dan', 'Sin, Wan-Yee Fion', 'Xu, Guo-Bing', 'Yang, Huang-Hua', 'Wong, Tin-yau', 'Pang, Xue-Wen', 'He, Xiao-Yan', 'Zhang, Hua-Gang', 'Ng, Joice Na Lee', 'Cheng, Chak-Sum Samuel', 'Ju, Jing', 'Meng, Li', 'Yang, Rui-Feng', 'Lai, Sik-To', 'Guo, Zhi-Hong', 'Xie, Yong', 'Chen, Wei-Feng']",,,,
,PMC,Cleavage Inhibition of the Murine Coronavirus Spike Protein by a Furin-Like Enzyme Affects Cell-Cell but Not Virus-Cell Fusion,http://dx.doi.org/10.1128/JVI.78.11.6048-6054.2004,PMC415802,,,"Cleavage of the mouse hepatitis coronavirus strain A59 spike protein was blocked in a concentration-dependent manner by a peptide furin inhibitor, indicating that furin or a furin-like enzyme is responsible for this process. While cell-cell fusion was clearly affected by preventing spike protein cleavage, virus-cell fusion was not, indicating that these events have different requirements.",,"['de Haan, Cornelis A. M.', 'Stadler, Konrad', 'Godeke, Gert-Jan', 'Bosch, Berend Jan', 'Rottier, Peter J. M.']",,,,
,PMC,Cleavage between Replicase Proteins p28 and p65 of Mouse Hepatitis Virus Is Not Required for Virus Replication,http://dx.doi.org/10.1128/JVI.78.11.5957-5965.2004,PMC415798,,,"The p28 and p65 proteins of mouse hepatitis virus (MHV) are the most amino-terminal protein domains of the replicase polyprotein. Cleavage between p28 and p65 has been shown to occur in vitro at cleavage site 1 (CS1), (247)Gly↓Val(248), in the polyprotein. Although critical residues for CS1 cleavage have been mapped in vitro, the requirements for cleavage have not been studied in infected cells. To define the determinants of CS1 cleavage and the role of processing at this site during MHV replication, mutations and deletions were engineered in the replicase polyprotein at CS1. Mutations predicted to allow cleavage at CS1 yielded viable virus that grew to wild-type MHV titers and showed normal expression and processing of p28 and p65. Mutant viruses containing predicted noncleaving mutations or a CS1 deletion were also viable but demonstrated delayed growth kinetics, reduced peak titers, decreased RNA synthesis, and small plaques compared to wild-type controls. No p28 or p65 was detected in cells infected with predicted noncleaving CS1 mutants or the CS1 deletion mutant; however, a new protein of 93 kDa was detected. All introduced mutations and the deletion were retained during repeated virus passages in culture, and no phenotypic reversion was observed. The results of this study demonstrate that cleavage between p28 and p65 at CS1 is not required for MHV replication. However, proteolytic separation of p28 from p65 is necessary for optimal RNA synthesis and virus growth, suggesting important roles for these proteins in the formation or function of viral replication complexes.",,"['Denison, Mark R.', 'Yount, Boyd', 'Brockway, Sarah M.', 'Graham, Rachel L.', 'Sims, Amy C.', 'Lu, XiaoTao', 'Baric, Ralph S.']",,,,
,PMC,Reverse Genetic Analysis of the Transcription Regulatory Sequence of the Coronavirus Transmissible Gastroenteritis Virus,http://dx.doi.org/10.1128/JVI.78.11.6061-6066.2004,PMC415797,,,"Coronavirus discontinuous transcription uses a highly conserved sequence (CS) in the joining of leader and body RNAs. Using a full-length infectious construct of transmissable gastroenteritis virus, the present study demonstrates that subgenomic transcription is heavily influenced by upstream flanking sequences and supports a mechanism of transcription attenuation that is regulated in part by a larger domain composed of primarily upstream flanking sequences which select appropriately positioned CS elements for synthesis of subgenomic RNAs.",,"['Curtis, Kristopher M.', 'Yount, Boyd', 'Sims, Amy C.', 'Baric, Ralph S.']",,,,
,PMC,Antisense Morpholino-Oligomers Directed against the 5′ End of the Genome Inhibit Coronavirus Proliferation and Growth†,http://dx.doi.org/10.1128/JVI.78.11.5891-5899.2004,PMC415795,,,"Conjugation of a peptide related to the human immunodeficiency virus type 1 Tat represents a novel method for delivery of antisense morpholino-oligomers. Conjugated and unconjugated oligomers were tested to determine sequence-specific antiviral efficacy against a member of the Coronaviridae, Mouse hepatitis virus (MHV). Specific antisense activity designed to block translation of the viral replicase polyprotein was first confirmed by reduction of luciferase expression from a target sequence-containing reporter construct in both cell-free and transfected cell culture assays. Peptide-conjugated morpholino-oligomers exhibited low toxicity in DBT astrocytoma cells used for culturing MHV. Oligomer administered at micromolar concentrations was delivered to >80% of cells and inhibited virus titers 10- to 100-fold in a sequence-specific and dose-responsive manner. In addition, targeted viral protein synthesis, plaque diameter, and cytopathic effect were significantly reduced. Inhibition of virus infectivity by peptide-conjugated morpholino was comparable to the antiviral activity of the aminoglycoside hygromycin B used at a concentration fivefold higher than the oligomer. These results suggest that this composition of antisense compound has therapeutic potential for control of coronavirus infection.",,"['Neuman, Benjamin W.', 'Stein, David A.', 'Kroeker, Andrew D.', 'Paulino, Amy D.', 'Moulton, Hong M.', 'Iversen, Patrick L.', 'Buchmeier, Michael J.']",,,,
,PMC,Serum hepatic enzyme manifestations in patients with severe acute respiratory syndrome: Retrospective analysis,http://dx.doi.org/10.3748/wjg.v10.i11.1652,PMC4572772,,,"AIM: To evaluate the hepatic function in patients with severe acute respiratory syndrome (SARS) and possible causes of hepatic disorder in these patients. METHODS: One hundred and eighty-two patients with SARS were employed in a retrospective study that investigated hepatic dysfunction. Liver alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactic dehydrogenase (LDH) were analyzed in these patients. Patients with different hospital treatments were further investigated. RESULTS: Of the 182 patients, 128 (70.3%) had abnormal ALT activity, 57 (31.3%) had abnormal AST activity and 87 (47.8%) had abnormal LDH activity. The peak of elevated hepatic enzyme activities occurred between the sixth day and the tenth day after the first day of reported fever. Of the 182 patients, 160 (87.9%) had been treated with antibiotics, 137 (75.2%) with Ribavirin, and 115 (63.2%) with methylpredisolone. There was no statistically significant correlation between the duration of Ribavirin treatement and hepatic dysfunction. CONCLUSION: Abnormal liver functions were common in patients with SARS and could be associated with virus replication in the liver.",,"['Cui, Hui-Juan', 'Tong, Xiao-Lin', 'Li, Ping', 'Hao, Ying-Xu', 'Chen, Xiao-Guang', 'Li, Ai-Guo', 'Zhang, Zhi-Yuan', 'Duan, Jun', 'Zhen, Min', 'Zhang, Bin', 'Hua, Chuan-Jin', 'Gong, Yue-Wen']",,,,
,PMC,In brief,,PMC420159,,,,,,,,,
,PMC,Structural characterization of the fusion-active complex of severe acute respiratory syndrome (SARS) coronavirus,http://dx.doi.org/10.1073/pnas.0402753101,PMC423260,,,"The causative agent of a recent outbreak of an atypical pneumonia, known as severe acute respiratory syndrome (SARS), has been identified as a coronavirus (CoV) not belonging to any of the previously identified groups. Fusion of coronaviruses with the host cell is mediated by the envelope spike protein. Two regions within the spike protein of SARS-CoV have been identified, showing a high degree of sequence conservation with the other CoV, which are characterized by the presence of heptad repeats (HR1 and HR2). By using synthetic and recombinant peptides corresponding to the HR1 and HR2 regions, we were able to characterize the fusion-active complex formed by this novel CoV by CD, native PAGE, proteolysis protection analysis, and size-exclusion chromatography. HR1 and HR2 of SARS-CoV associate into an antiparallel six-helix bundle, with structural features typical of the other known class I fusion proteins. We have also mapped the specific boundaries of the region, within the longer HR1 domain, making contact with the shorter HR2 domain. Notably, the inner HR1 coiled coil is a stable α-helical domain even in the absence of interaction with the HR2 region. Inhibitors binding to HR regions of fusion proteins have been shown to be efficacious against many viruses, notably HIV. Our results may help in the design of anti-SARS therapeutics.",,"['Ingallinella, Paolo', 'Bianchi, Elisabetta', 'Finotto, Marco', 'Cantoni, Giovanna', 'Eckert, Debra M.', 'Supekar, Vinit M.', 'Bruckmann, Chiara', 'Carfi, Andrea', 'Pessi, Antonello']",,,,
,PMC,"Breaches of safety regulations are probable cause of recent SARS outbreak, WHO says",,PMC416634,,,,,"Parry, Jane",,,,
,PMC,Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides,http://dx.doi.org/10.1073/pnas.0400576101,PMC420415,,,"The coronavirus SARS-CoV is the primary cause of the life-threatening severe acute respiratory syndrome (SARS). With the aim of developing therapeutic agents, we have tested peptides derived from the membrane-proximal (HR2) and membrane-distal (HR1) heptad repeat region of the spike protein as inhibitors of SARS-CoV infection of Vero cells. It appeared that HR2 peptides, but not HR1 peptides, were inhibitory. Their efficacy was, however, significantly lower than that of corresponding HR2 peptides of the murine coronavirus mouse hepatitis virus (MHV) in inhibiting MHV infection. Biochemical and electron microscopical analyses showed that, when mixed, SARS-CoV HR1 and HR2 peptides assemble into a six-helix bundle consisting of HR1 as a central triple-stranded coiled coil in association with three HR2 α-helices oriented in an antiparallel manner. The stability of this complex, as measured by its resistance to heat dissociation, appeared to be much lower than that of the corresponding MHV complex, which may explain the different inhibitory potencies of the HR2 peptides. Analogous to other class I viral fusion proteins, the six-helix complex supposedly represents a postfusion conformation that is formed after insertion of the fusion peptide, proposed here for coronaviruses to be located immediately upstream of HR1, into the target membrane. The resulting close apposition of fusion peptide and spike transmembrane domain facilitates membrane fusion. The inhibitory potency of the SARS-CoV HR2-peptides provides an attractive basis for the development of a therapeutic drug for SARS.",,"['Bosch, Berend Jan', 'Martina, Byron E. E.', 'van der Zee, Ruurd', 'Lepault, Jean', 'Haijema, Bert Jan', 'Versluis, Cees', 'Heck, Albert J. R.', 'de Groot, Raoul', 'Osterhaus, Albert D. M. E.', 'Rottier, Peter J. M.']",,,,
,PMC,H5N1 influenza: A protean pandemic threat,http://dx.doi.org/10.1073/pnas.0402443101,PMC419573,,,"Infection with avian influenza A virus of the H5N1 subtype (isolates A/HK/212/03 and A/HK/213/03) was fatal to one of two members of a family in southern China in 2003. This incident was preceded by lethal outbreaks of H5N1 influenza in waterfowl, which are the natural hosts of these viruses and, therefore, normally have asymptomatic infection. The hemagglutinin genes of the A/HK/212/03-like viruses isolated from humans and waterfowl share the lineage of the H5N1 viruses that caused the first known cases of human disease in Hong Kong in 1997, but their internal protein genes originated elsewhere. The hemagglutinin of the recent human isolates has undergone significant antigenic drift. Like the 1997 human H5N1 isolates, the 2003 human H5N1 isolates induced the overproduction of proinflammatory cytokines by primary human macrophages in vitro, whereas the precursor H5N1 viruses and other H5N1 reassortants isolated in 2001 did not. The acquisition by the viruses of characteristics that enhance virulence in humans and waterfowl and their potential for wider distribution by infected migrating birds are causes for renewed pandemic concern.",,"['Guan, Y.', 'Poon, L. L. M.', 'Cheung, C. Y.', 'Ellis, T. M.', 'Lim, W.', 'Lipatov, A. S.', 'Chan, K. H.', 'Sturm-Ramirez, K. M.', 'Cheung, C. L.', 'Leung, Y. H. C.', 'Yuen, K. Y.', 'Webster, R. G.', 'Peiris, J. S. M.']",,,,
,PMC,Experts urge action to stop animal diseases infecting humans,,PMC411137,,,,,"Fleck, Fiona",,,,
,PMC,The Return of the White Plague: Global Poverty and the New Tuberculosis,,PMC411117,,,,,"Mitchell, David",,,,
,PMC,Critical care medicine mailing list: growth of an online forum,,PMC411101,,,,,"['DeWitt, Anthony L', 'Gunn, Scott R', 'Hopkins, Phil', 'Streat, Stephen']",,,,
,PMC,The professor of “telepreventive medicine”,,PMC411088,,,"The Supercourse website collects hundreds of lectures on public health delivered by a global faculty of experts. Its founder, Ron LaPorte, tells Gavin Yamey about running a “university without walls”",,"Yamey, Gavin",,,,
,PMC,A lawyer with the Hygeia touch,,PMC406316,,,Health professionals were initially disappointed when the top public health job in Europe went to a lawyer. But David Byrne's commitment has won them over. Rory Watson reports,,"Watson, Rory",,,,
,PMC,In brief,,PMC406312,,,,,,,,,
,PMC,What’s New About the “New Public Health”?,,PMC1448321,,,"From its origins, when public health was integral to societies’ social structures, through the sanitary movement and contagion eras, when it evolved as a separate discipline, to the “new public health” era, when health promotion projects like Healthy Cities appear to be steering the discipline back to society’s social structure, public health seems to have come full circle. It is this observation that has led some to ask, “What’s new about the ‘new public health’?” This article addresses the question by highlighting what is new about the health promotion era—including adapted components of previous eras that have been incorporated into its core activities—and its suitability in addressing established and emerging public health threats.",,"Awofeso, Niyi",,,,
,PMC,Chinese authorities on alert as SARS breaks out again,,PMC403836,,,,,"Parry, Jane",,,,
,PMC,Innovation and challenges in funding rapid research responses to emerging infectious diseases: Lessons learned from the outbreak of severe acute respiratory syndrome,,PMC2094971,,,"Although the local public health response to the severe acute respiratory syndrome outbreak in Canada was critical to the diagnosis, management and treatment of patients, such a rapid research response required a national effort to engage the research and stakeholder communities. The Canadian research effort, coordinated through the Institute of Infection and Immunity of the Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research, has provided insight into the mechanisms required to ensure the rapid development of strategical initiatives in response to emerging infectious diseases. It has also provided a rational basis to set up a national network to be engaged if needed in the future.",,"Singh, Bhagirath",,,,
,PMC,HIV: A journey just begun,,PMC2094968,,,,,"Nicolle, Lindsay E",,,,
,PMC,Severe Acute Respiratory Syndrome: Clinical and Laboratory Manifestations,,PMC1904416,,,"Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease with significant morbidity and mortality. An epidemic in 2003 affected 8,098 patients in 29 countries with 774 deaths. The aetiological agent is a new coronavirus spread by droplet transmission. Clinical and general laboratory manifestations included fever, chills, rigor, myalgia, malaise, diarrhoea, cough, dyspnoea, pneumonia, lymphopenia, neutrophilia, thrombocytopenia, and elevated serum lactate dehydrogenase (LD), alanine aminotransferase (ALT) and creatine kinase (CK) activities. Treatment has been empirical; initial potent antibiotic cover, followed by simultaneous ribavirin and corticosteroids, with or without pulse high-dose methylprednisolone, have been used. The postulated disease progression comprises (1) active viral infection, (2) hyperactive immune response, and (3) recovery or pulmonary destruction and death. We investigated serum LD isoenzymes and blood lymphocyte subsets of SARS patients, and found LD1 activity as the best biochemical prognostic indicator for death, while CD3+, CD4+, CD8+ and natural killer cell counts were promising predictors for intensive care unit (ICU) admission. Plasma cytokine and chemokine profiles showed markedly elevated Th1 cytokine interferon (IFN)-γ, inflammatory cytokines interleukin (IL)-1β, IL-6 and IL-12, neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-γ-inducible protein-10 (IP-10) for at least two weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumor necrosis factor (TNF)-α and anti-inflammatory cytokine IL-10. Corticosteroid reduced IL-8, MCP-1 and IP-10 concentrations from 5–8 days after treatment. Measurement of biochemical markers of bone metabolism demonstrated significant but transient increase in bone resorption from Day 28–44 after onset of fever, when pulse steroid was most frequently given. With tapering down of steroid therapy, there was a decrease in bone resorption marker together with an increase in bone formation markers round Day 50, suggesting that some of the bone loss might be reversed. Our research studies on the chemical pathology and clinical immunology of SARS should have implications for the pathophysiology and therapy of this potentially lethal infection.",,"['Lam, Christopher W K', 'Chan, Michael H M', 'Wong, Chun K']",,,,
,PMC,The Laboratory Diagnosis of Severe Acute Respiratory Syndrome: Emerging Laboratory Tests for an Emerging Pathogen,,PMC1904415,,,"The 2003 pandemic of Severe Acute Respiratory Syndrome (SARS) profiled the ability of modern diagnostic microbiology and molecular biology to identify, isolate and characterize, within weeks, a previously unknown viral infectious pathogen. The culprit, SARS coronavirus (SARS-CoV), was detected in patient specimens by traditional cell culture using an unusual cell line for respiratory viruses, Vero E6, and by reverse transcriptase polymerase chain reaction (RT-PCR) targeting the polymerase 1 B region of the genome. In addition, serologic assays were rapidly developed, and the genome of this large virus was sequenced within one month of its spread to North America. At the present time, diagnostics have progressed to the point that RT-PCR has a sensitivity approaching 80% within the first few days of onset of illness, while serology has a sensitivity close to 100% on convalescent sera taken >21 days after illness onset. Viral culture remains a method confined to biosafety level III laboratories. The specificity of RT-PCR and serology remains to be conclusively defined, but in most studies to date seems to be >90%. Serologic cross-reactivity with human coronaviruses causing the common cold may be a problem with some serologic assays. The early development of SARS-CoV diagnostics is now being replaced by refinement and optimization of these assays. Although at the present time we do not have a test that will definitively rule in or rule out SARS at the time of initial presentation of a patient with a respiratory infection, modifications of existing assays will hopefully result in our ability to make this diagnosis with a high degree of accuracy in the future.",,"['Richardson, Susan E.', 'Tellier, Raymond', 'Mahony, James']",,,,
,PMC,Molecular Epidemiology of the Coronavirus Associated with Severe Acute Respiratory Syndrome: A Review of Data from The Chinese University of Hong Kong,,PMC1904414,,,"The epidemic of the severe acute respiratory syndrome (SARS) has swept through the globe with more than 8000 reported probable cases. In Hong Kong, the hardest hit areas included our teaching hospital and the Amoy Gardens apartment complex. A novel coronavirus, SARS-coronavirus (SARS-CoV), with a single-stranded plus sense RNA genome, was promptly implicated as the causative agent and subsequently fulfilled Koch's postulates. To aid the understanding of SARS-CoV, groups of investigators rapidly sequenced viral isolates around the world. We were the third group in the world to release the complete SARS-CoV genome sequence (isolate CUHK-W1) on the world-wide web. With other isolates from patients of distinct epidemiological backgrounds, we additionally sequenced four complete (CUHK-Su10, CUHK-AG01, CUHK-AG02, CUHK-AG03) and two partial SARS-CoV genomes. The reviewed data obtained from representative patients from the hospital and community outbreaks has documented the evolution of the virus in this epidemic. Their sequence variations also revealed a remarkable epidemiological correlation. We demonstrate that sequence variations in the SARS-CoV genome can be applied as a powerful molecular tool in tracing the route of transmission, when used adjunctively with standard epidemiology.",,"['Chim, Stephen S.C.', 'Lo, Y.M. Dennis', None]",,,,
,PMC,Heat Shock Protein and Gliadin Peptide Promote Development of Peptidase Antibodies in Children with Autism and Patients with Autoimmune Disease,http://dx.doi.org/10.1128/CDLI.11.3.515-524.2004,PMC404567,,,"Searching for a mechanism underlying autoimmunity in autism, we postulated that gliadin peptides, heat shock protein 60 (HSP-60), and streptokinase (SK) bind to different peptidases resulting in autoantibody production against these components. We assessed this hypothesis in patients with autism and in those with mixed connective tissue diseases. Associated with antigliadin and anti-HSP antibodies, children with autism and patients with autoimmune disease developed anti-dipeptidylpeptidase I (DPP I), anti-dipeptidylpeptidase IV (DPP IV [or CD26]) and anti-aminopeptidase N (CD13) autoantibodies. A significant percentage of autoimmune and autistic sera were associated with elevated immunoglobulin G (IgG), IgM, or IgA antibodies against three peptidases, gliadin, and HSP-60. These antibodies are specific, since immune absorption demonstrated that only specific antigens (e.g., DPP IV absorption of anti-DPP IV), significantly reduced IgG, IgM, and IgA antibody levels. For direct demonstration of SK, HSP-60, and gliadin peptide binding to DPP IV, microtiter wells coated with DPP IV were reacted with SK, HSP-60, and gliadin. They were then reacted with anti-DPP IV or anti-SK, anti-HSP, and antigliadin antibodies. Adding SK, HSP-60, and gliadin peptides to DPP IV resulted in 27 to 43% inhibition of the DPP IV-anti-DPP IV reaction, but DPP IV-positive peptides caused 18 to 20% enhancement of antigen-antibody reactions. We propose that (i) superantigens (e.g., SK and HSP-60) and dietary proteins (e.g., gliadin peptides) in individuals with predisposing HLA molecules bind to aminopeptidases and (ii) they induce autoantibodies to peptides and tissue antigens. Dysfunctional membrane peptidases and autoantibody production may result in neuroimmune dysregulation and autoimmunity.",,"['Vojdani, Aristo', 'Bazargan, Mohsen', 'Vojdani, Elroy', 'Samadi, John', 'Nourian, Alen A.', 'Eghbalieh, Navid', 'Cooper, Edwin L.']",,,,
,PMC,"Impact of an outbreak of severe acute respiratory syndrome on a hospital in Taiwan, ROC",http://dx.doi.org/10.1136/emj.2003.011122,PMC1726342,,,"Study objective: To estimate the impact of the severe acute respiratory syndrome (SARS) outbreak in early 2003 on a tertiary care hospital in Taiwan, ROC. Methods: The study estimated the utilisation of resources related to infection control, SARS related medical services, and routine medical services, and SARS related medical outcomes at National Cheng Kung University Hospital (NCKUH) from 25 March to 16 June 2003 through a cross sectional survey of hospital records. Results: A mean of 5100 persons per day (95%CI 4580 to 5610) underwent fever screening at the outpatient and emergency department (ED) entrances to the hospital, of which 35 per day (95% CI 30 to 40) were referred for further evaluation for suspected or probable SARS. ED isolation surge capacity was created via 12 new beds outside the ED: eight for SARS assessment, three for patients awaiting inhospital bed assignment, and one for resuscitation. A total of 382 patients were fully evaluated for suspected or probable SARS outside the ED, of which 27 were admitted. The mean numbers of outpatient clinic patient visits, ED visits, ED trauma patient visits, ED admissions, hospital admissions, and operative procedures decreased during the outbreak. Thirty eight patients were hospitalised with suspected SARS, of which three received the final diagnosis of probable SARS. Two patients with probable SARS died. No cases of nosocomial SARS transmission occurred. Conclusions: This SARS outbreak was associated with substantial use of hospital and ED resources aimed at infection control, comparatively less use of resources related to the medical care of patients with suspected or probable SARS, and decreased use of routine medical services.",,"['Tsai, M', 'Arnold, J', 'Chuang, C', 'Chi, C', 'Liu, C', 'Yang, Y']",,,,
,PMC,Sockeye: A 3D Environment for Comparative Genomics,http://dx.doi.org/10.1101/gr.1890304,PMC479126,,,"Comparative genomics techniques are used in bioinformatics analyses to identify the structural and functional properties of DNA sequences. As the amount of available sequence data steadily increases, the ability to perform large-scale comparative analyses has become increasingly relevant. In addition, the growing complexity of genomic feature annotation means that new approaches to genomic visualization need to be explored. We have developed a Java-based application called Sockeye that uses three-dimensional (3D) graphics technology to facilitate the visualization of annotation and conservation across multiple sequences. This software uses the Ensembl database project to import sequence and annotation information from several eukaryotic species. A user can additionally import their own custom sequence and annotation data. Individual annotation objects are displayed in Sockeye by using custom 3D models. Ensembl-derived and imported sequences can be analyzed by using a suite of multiple and pair-wise alignment algorithms. The results of these comparative analyses are also displayed in the 3D environment of Sockeye. By using the Java3D API to visualize genomic data in a 3D environment, we are able to compactly display cross-sequence comparisons. This provides the user with a novel platform for visualizing and comparing genomic feature organization.",,"['Montgomery, Stephen B.', 'Astakhova, Tamara', 'Bilenky, Mikhail', 'Birney, Ewan', 'Fu, Tony', 'Hassel, Maik', 'Melsopp, Craig', 'Rak, Marcin', 'Robertson, A. Gordon', 'Sleumer, Monica', 'Siddiqui, Asim S.', 'Jones, Steven J.M.']",,,,
,PMC,"Type-A CpG oligonucleotides activate exclusively porcine natural interferon-producing cells to secrete interferon-α, tumour necrosis factor-α and interleukin-12",http://dx.doi.org/10.1111/j.1365-2567.2004.01856.x,PMC1782461,,,"Natural interferon-producing cells (NIPC), also referred to as immature plasmacytoid dendritic cells (PDC), constitute a small population of leucocytes secreting high levels of type I interferons in response to certain danger signals. Amongst these signals are those from DNA containing unmethylated CpG motifs. The present work demonstrated that the CpG oligonucleotides (CpG-ODN) 2216, D32 and D19 induce high amounts of interferon-α (IFN-α), tumour-necrosis factor-α (TNF-α) and interleukin (IL)-12 in porcine peripheral blood mononuclear cells (PBMCs). Swine workshop cluster 3 (SWC3)(1ow) CD4(high) cells, with high IL-3-binding activity, representing NIPC, were the exclusive cytokine-producing cells responding to the CpG-ODN. These cells did not express CD6, CD8 or CD45RA. Importantly, monocyte-derived DC did not respond to CpG-ODN by secretion of IFN-α or TNF-α or by the up-regulation of costimulatory molecule expression. CpG-ODN up-regulated MHC class II and CD80/86 expression on the NIPC, but were unable to promote NIPC survival. Interestingly, certain CpG-ODN, incapable of inducing NIPC to secrete IFN-α or up-regulate MHC class II and CD80/86, did promote NIPC viability. Taken together, the influence of CpG-ODN on porcine NIPC, monocytes and myeloid DCs relates to that observed with their human equivalents. These results represent an important basis for the application of CpG-ODN as adjuvants for the formulation of novel vaccines and demonstrate the importance of the pig as an alternative animal model for this approach.",,"['Guzylack-Piriou, Laurence', 'Balmelli, Carole', 'McCullough, Kenneth C', 'Summerfield, Artur']",,,,
,PMC,Detection of Specific Antibodies to Severe Acute Respiratory Syndrome (SARS) Coronavirus Nucleocapsid Protein for Serodiagnosis of SARS Coronavirus Pneumonia,http://dx.doi.org/10.1128/JCM.42.5.2306-2309.2004,PMC404667,,,"We report the evaluation of recombinant severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) nucleocapsid protein enzyme-linked immunosorbent assay (ELISA)-based antibody tests for serodiagnosis of SARS-CoV pneumonia and compare the sensitivities and specificities of this ELISA for detection of immunoglobulin G (IgG), IgM, IgA, and their combinations with serum samples from 149 healthy blood donors who donated blood 3 years ago as controls and 106 SARS-CoV pneumonia patients in Hong Kong. The specificities of the ELISA for IgG, IgM, and IgA detection were 95.3, 96.6, and 96.6%, respectively, with corresponding sensitivities of 94.3, 59.4, and 60.4%, respectively. The present ELISA appears to be a sensitive test for serodiagnosis of SARS-CoV pneumonia, is much more economical and less labor-intensive than the indirect immunofluorescence assay, and does not require cultivation of SARS-CoV.",,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Wong, Beatrice H. L.', 'Tsoi, Hoi-wah', 'Fung, Ami M. Y.', 'Chan, Kwok-hung', 'Tam, Victoria K. P.', 'Peiris, J. S. Malik', 'Yuen, Kwok-yung']",,,,
,PMC,Development and Evaluation of a Novel Loop-Mediated Isothermal Amplification Method for Rapid Detection of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JCM.42.5.1956-1961.2004,PMC404656,,,"The development and evaluation of a one-step single-tube accelerated real-time quantitative reverse transcription (RT) loop-mediated isothermal amplification (LAMP) assay is reported for rapid detection of the severe acute respiratory syndrome coronavirus (SARS-CoV) replicase gene. A total of 49 samples (15 throat washes, 13 throat swabs, and 21 combined throat and nasal swabs) collected from patients admitted to the Hanoi-French and Ninhbinh hospitals in Vietnam during the SARS epidemic were evaluated and compared to conventional RT-PCR. The RT-LAMP assay demonstrated 100-fold-greater sensitivity, with a detection limit of 0.01 PFU. The sensitivity and specificity of RT-LAMP assay for detecting viral RNA in clinical specimens with regard to RT-PCR were 100 and 87%, respectively. The specificity of the RT-LAMP assay was further validated by restriction analysis as well as nucleotide sequencing of the amplified product. The concentration of virus in most of the clinical samples was 0.1 PFU (0.1 to 10(2) PFU), as determined from the standard curve of SARS RT-LAMP and based on the time of positivity. The assay procedure is quite simple, wherein the amplification is carried out in a single tube under isothermal conditions at 63°C, and the result can be obtained in less than 1 h (as early as 11 min). Thus, the RT-LAMP assay reported here has the advantages of rapid amplification, simple operation, and easy detection and will be useful for rapid and reliable clinical diagnosis of SARS-CoV in developing countries.",,"['Thai, Hong Thi Cam', 'Le, Mai Quynh', 'Vuong, Cuong Duc', 'Parida, Manmohan', 'Minekawa, Harumi', 'Notomi, Tsugunori', 'Hasebe, Futoshi', 'Morita, Kouichi']",,,,
,PMC,Comparison of Two Real-Time Quantitative Assays for Detection of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JCM.42.5.2094-2100.2004,PMC404649,,,"The new severe acute respiratory syndrome (SARS) coronavirus (CoV), described in February 2003, infected a total of 8,439 people. A total of 812 people died due to respiratory insufficiency. Close contact with symptomatic patients appeared to be the main route of transmission. However, potential transmission by blood transfusion could not be definitely excluded. Two real-time SARS-specific PCR assays were assessed for their sensitivities, agreement of test results, and intra-assay variabilities. Both assays rely on reverse transcription and amplification of extracted RNA. Dilutions of gamma-irradiated cell culture supernatants of SARS CoV-infected Vero E6 cells were prepared to determine the precisions, linear ranges, and accuracies of the assays. The linear range for the Artus RealArt HPA-Coronavirus assay (Artus assay) was 1 × 10(2) to 1 × 10(7) copies/ml, and that for the Roche LightCycler SARS CoV Quantification kit (Roche assay) was 1 × 10(4) to 2 × 10(8) copies/ml. The detection limit of the Roche assay was 3,982.1 copies/ml, whereas that of the Artus assay was 37.8 copies/ml. Detection limits were calculated with a standard preparation that was recommended for use by the World Health Organization. However, quantification of CoV in this preparation may be imprecise. In summary, both assays are suitable for quantitative measurement of SARS CoV at the high concentrations expected in sputum samples. The Artus assay is also suitable for detection of SARS CoV at the low concentrations found in serum samples.",,"['Hourfar, Michael K.', 'Roth, W. Kurt', 'Seifried, Erhard', 'Schmidt, Michael']",,,,
,PMC,Evaluation of Advanced Reverse Transcription-PCR Assays and an Alternative PCR Target Region for Detection of Severe Acute Respiratory Syndrome-Associated Coronavirus,http://dx.doi.org/10.1128/JCM.42.5.2043-2047.2004,PMC404639,,,"First-generation reverse transcription-PCR (RT-PCR) assays for severe acute respiratory syndrome-associated coronavirus (SARS-CoV) gave false-negative results in a considerable fraction of patients. In the present study, we evaluated two second-generation, replicase (R) gene-based, real-time RT-PCR test kits—the RealArt HPA coronavirus LC kit (Artus, Hamburg, Germany) and the LightCycler SARS-CoV quantification kit (Roche, Penzberg, Germany)—and a real-time RT-PCR assay for the nucleocapsid (N) gene. Detecting the N-gene RNA might be advantageous due to its high abundance in cells. The kits achieved sensitivities of 70.8% (Artus) and 67.1% (Roche) in 66 specimens from patients with confirmed SARS (samples primarily from the upper and lower respiratory tract and stool). The sensitivity of the N-gene assay was 74.2%. The differences in all of the sensitivities were not statistically significant (P = 0.680 [analysis of variance]). Culture cells initially contained five times more N- than R-gene RNA, but the respective levels converged during 4 days of virus replication. In clinical samples the median concentrations of R- and N-gene RNA, respectively, were 1.2 × 10(6) and 2.8 × 10(6) copies/ml (sputum and endotracheal aspirates), 4.3 × 10(4) and 5.5 × 10(4) copies/ml (stool), and 5.5 × 10(2) and 5.2 × 10(2) copies/sample (throat swabs and saliva). Differences between the samples types were significant but not between the types of target RNA. All (n = 12) samples from the lower respiratory tract tested positive in all tests. In conclusion, the novel assays are more sensitive than the first-generation tests, but they still do not allow a comprehensive ruling out of SARS. Methods for the routine sampling of sputum without infection risk are needed to improve SARS RT-PCR.",,"['Drosten, Christian', 'Chiu, Lily-Lily', 'Panning, Marcus', 'Leong, Hoe Nam', 'Preiser, Wolfgang', 'Tam, John S.', 'Günther, Stephan', 'Kramme, Stefanie', 'Emmerich, Petra', 'Ng, Wooi Loon', 'Schmitz, Herbert', 'Koay, Evelyn S. C.']",,,,
,PMC,"Use of the DNA Flow-Thru Chip, a Three-Dimensional Biochip, for Typing and Subtyping of Influenza Viruses",http://dx.doi.org/10.1128/JCM.42.5.2173-2185.2004,PMC404638,,,"Influenza A viruses, which are further subtyped on the basis of antigenic differences in external hemagglutinin and neuraminidase glycoproteins, and influenza B viruses are prominent among the viral causes of respiratory diseases and can cause a wide spectrum of illness. Each year these viruses are responsible for recurrent epidemics, frequently in association with genetic variation. There is a requirement for sensitive and rapid diagnostic techniques in order to improve both the diagnosis of infections and the quality of surveillance systems. A new three-dimensional biochip platform (Flow-Thru Chip; MetriGenix) was used to develop a rapid and reliable molecular method for the typing and subtyping of influenza viruses. Oligonucleotide probes immobilized in microchannels of a silicon wafer were selected to recognize multiple fragments of the influenza A virus matrix protein gene; the influenza B virus NS gene; the H1, H3, and H5 hemagglutinin genes; and the N1 and N2 neuraminidase genes. Biotinylated amplicons resulting from either multiplex or random reverse transcription-PCR were hybridized to arrayed oligonucleotides on the influenza virus chip before they were stained with horseradish peroxidase-streptavidin and were imaged by use of a chemiluminescent substrate. The chip analysis procedure, from the time of pipetting of the sample into the chip cartridge to the time of analysis of the results, was performed in less than 5 h. The random PCR exhibited a higher level of performance than the multiplex PCR in terms of the specificity of product hybridization to the influenza virus chip. Analysis of influenza A viruses (H1N1, H3N2, H1N2, and H5N1) and influenza B viruses showed that this microarray-based method is capable of the rapid and unambiguous identification of all types and subtypes of viruses by use of random PCR products. The redundancy of the probes designed for each gene selected yielded an additional criterion of confidence for the subtyping of viruses which are known for antigenic variations in some of their components.",,"['Kessler, Nicole', 'Ferraris, Olivier', 'Palmer, Kevin', 'Marsh, Wayne', 'Steel, Adam']",,,,
,PMC,Reverse Transcriptase PCR Diagnostic Assay for the Coronavirus Associated with Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1128/JCM.42.5.1994-1999.2004,PMC404607,,,"Recent outbreaks of severe acute respiratory syndrome (SARS) have spurred intense research efforts around the world to deal with the serious threat to health posed by this novel coronavirus. A rapid, reliable diagnostic assay is needed for monitoring the spread of the disease. Here we report a method for eliminating false-negative results and increasing test sensitivity, based on the hypothesis that the message encoded by the nucleocapsid (N) gene is the most abundant during viral infection. Nasopharyngeal aspirates and stool samples were obtained from suspected SARS patients with major clinical symptoms and a significant history of close contact with infected patients. Total RNAs were extracted in a 96-well format, together with pig kidney epithelial (PK-15) cells as an internal control for extraction efficiency. PCR inhibitors were removed by ethanol precipitation, and a PCR for the pig β-actin gene was used as a positive control for all clinical samples. Samples were analyzed by a reverse transcriptase PCR assay. Northern blot analysis was performed to demonstrate differences in subgenomic transcripts of the virus, and a real-time quantitative PCR was employed to compare the sensitivities of two loci (1b and N). The detection rate of the assay reached 44.4% on day 9 after the onset of the disease. The diagnostic PCR amplifying the N gene gave an average of a 26.0% (6.3 to 60.0%) stronger intensity signal than that for the 1b gene. In conclusion, the nucleocapsid gene represents an additional sensitive molecular marker for the diagnosis of the SARS coronavirus and can be further adapted for use in a high-throughput platform assay.",,"['Hui, Raymond K. H.', 'Zeng, Fanya', 'Chan, Charis M. N.', 'Yuen, K. Y.', 'Peiris, Joseph S. M.', 'Leung, Frederick C. C.']",,,,
,PMC,Antigenic Cross-Reactivity between the Nucleocapsid Protein of Severe Acute Respiratory Syndrome (SARS) Coronavirus and Polyclonal Antisera of Antigenic Group I Animal Coronaviruses: Implication for SARS Diagnosis,http://dx.doi.org/10.1128/JCM.42.5.2351-2352.2004,PMC404591,,,,,"['Sun, Z. F.', 'Meng, X. J.']",,,,
,PMC,Use of disposable face masks for public health protection against SARS,,PMC1732776,,,,,"Lange, J",,,,
,PMC,Violence against women: the health sector responds,,PMC1732761,,,,,"Vives, C",,,,
,PMC,ActivEpi CD ROM and ActivEpi companion textbook,,PMC1732755,,,,,"de los, Angeles Ro... M",,,,
,PMC,Receptor-Dependent Coronavirus Infection of Dendritic Cells,http://dx.doi.org/10.1128/JVI.78.10.5486-5490.2004,PMC400329,,,"In several mammalian species, including humans, coronavirus infection can modulate the host immune response. We show a potential role of dendritic cells (DC) in murine coronavirus-induced immune modulation and pathogenesis by demonstrating that the JAW SII DC line and primary DC from BALB/c mice and p/p mice with reduced expression of the murine coronavirus receptor, murine CEACAM1a, are susceptible to murine coronavirus infection by a receptor-dependent pathway.",,"['Turner, Brian C.', 'Hemmila, Erin M.', 'Beauchemin, Nicole', 'Holmes, Kathryn V.']",,,,
,PMC,Generation and Characterization of DNA Vaccines Targeting the Nucleocapsid Protein of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.78.9.4638-4645.2004,PMC387705,,,"Severe acute respiratory syndrome (SARS) is a serious threat to public health and the economy on a global scale. The SARS coronavirus (SARS-CoV) has been identified as the etiological agent for SARS. Thus, vaccination against SARS-CoV may represent an effective approach to controlling SARS. DNA vaccines are an attractive approach for SARS vaccine development, as they offer many advantages over conventional vaccines, including stability, simplicity, and safety. Our investigators have previously shown that DNA vaccination with antigen linked to calreticulin (CRT) dramatically enhances major histocompatibility complex class I presentation of linked antigen to CD8(+) T cells. In this study, we have employed this CRT-based enhancement strategy to create effective DNA vaccines using SARS-CoV nucleocapsid (N) protein as a target antigen. Vaccination with naked CRT/N DNA generated the most potent N-specific humoral and T-cell-mediated immune responses in vaccinated C57BL/6 mice among all of the DNA constructs tested. Furthermore, mice vaccinated with CRT/N DNA were capable of significantly reducing the titer of challenging vaccinia virus expressing the N protein of the SARS virus. These results show that a DNA vaccine encoding CRT linked to a SARS-CoV antigen is capable of generating strong N-specific humoral and cellular immunity and may potentially be useful for control of infection with SARS-CoV.",,"['Kim, Tae Woo', 'Lee, Jin Hyup', 'Hung, Chien-Fu', 'Peng, Shiwen', 'Roden, Richard', 'Wang, Mei-Cheng', 'Viscidi, Raphael', 'Tsai, Ya-Chea', 'He, Liangmei', 'Chen, Pei-Jer', 'Boyd, David A. K.', 'Wu, T.-C.']",,,,
,PMC,Smallpox DNA Vaccine Protects Nonhuman Primates against Lethal Monkeypox,http://dx.doi.org/10.1128/JVI.78.9.4433-4443.2004,PMC387704,,,"Two decades after a worldwide vaccination campaign was used to successfully eradicate naturally occurring smallpox, the threat of bioterrorism has led to renewed vaccination programs. In addition, sporadic outbreaks of human monkeypox in Africa and a recent outbreak of human monkeypox in the U.S. have made it clear that naturally occurring zoonotic orthopoxvirus diseases remain a public health concern. Much of the threat posed by orthopoxviruses could be eliminated by vaccination; however, because the smallpox vaccine is a live orthopoxvirus vaccine (vaccinia virus) administered to the skin, the vaccine itself can pose a serious health risk. Here, we demonstrate that rhesus macaques vaccinated with a DNA vaccine consisting of four vaccinia virus genes (L1R, A27L, A33R, and B5R) were protected from severe disease after an otherwise lethal challenge with monkeypox virus. Animals vaccinated with a single gene (L1R) which encodes a target of neutralizing antibodies developed severe disease but survived. This is the first demonstration that a subunit vaccine approach to smallpox-monkeypox immunization is feasible.",,"['Hooper, J. W.', 'Thompson, E.', 'Wilhelmsen, C.', 'Zimmerman, M.', 'Ichou, M. Ait', 'Steffen, S. E.', 'Schmaljohn, C. S.', 'Schmaljohn, A. L.', 'Jahrling, P. B.']",,,,
,PMC,Amino Acids 270 to 510 of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Are Required for Interaction with Receptor,http://dx.doi.org/10.1128/JVI.78.9.4552-4560.2004,PMC387703,,,"A novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), has recently been identified as the causative agent of severe acute respiratory syndrome (SARS). SARS-CoV appears similar to other coronaviruses in both virion structure and genome organization. It is known for other coronaviruses that the spike (S) glycoprotein is required for both viral attachment to permissive cells and for fusion of the viral envelope with the host cell membrane. Here we describe the construction and expression of a soluble codon-optimized SARS-CoV S glycoprotein comprising the first 1,190 amino acids of the native S glycoprotein (S(1190)). The codon-optimized and native S glycoproteins exhibit similar molecular weight as determined by Western blot analysis, indicating that synthetic S glycoprotein is modified correctly in a mammalian expression system. S(1190) binds to the surface of Vero E6 cells, a cell permissive to infection, as demonstrated by fluorescence-activated cell sorter analysis, suggesting that S(1190) maintains the biologic activity present in native S glycoprotein. This interaction is blocked with serum obtained from recovering SARS patients, indicating that the binding is specific. In an effort to map the ligand-binding domain of the SARS-CoV S glycoprotein, carboxy- and amino-terminal truncations of the S(1190) glycoprotein were constructed. Amino acids 270 to 510 were the minimal receptor-binding region of the SARS-CoV S glycoprotein as determined by flow cytometry. We speculate that amino acids 1 to 510 of the SARS-CoV S glycoprotein represent a unique domain containing the receptor-binding site (amino acids 270 to 510), analogous to the S1 subunit of other coronavirus S glycoproteins.",,"['Babcock, Gregory J.', 'Esshaki, Diana J.', 'Thomas, William D.', 'Ambrosino, Donna M.']",,,,
,PMC,Norwalk Virus N-Terminal Nonstructural Protein Is Associated with Disassembly of the Golgi Complex in Transfected Cells,http://dx.doi.org/10.1128/JVI.78.9.4827-4837.2004,PMC387691,,,"Norwalk virus is the prototype strain for members of the genus Norovirus in the family Caliciviridae, which are associated with epidemic gastroenteritis in humans. The nonstructural protein encoded in the N-terminal region of the first open reading frame (ORF1) of the Norwalk virus genome is analogous in gene order to proteins 2A and 2B of the picornaviruses; the latter is known for its membrane-associated activities. Confocal microscopy imaging of cells transfected with a vector plasmid that provided expression of the entire Norwalk virus N-terminal protein (amino acids 1 to 398 of the ORF1 polyprotein) showed colocalization of this protein with cellular proteins of the Golgi apparatus. Furthermore, this colocalization was characteristically associated with a visible disassembly of the Golgi complex into discrete aggregates. Deletion of a predicted hydrophobic region (amino acids 360 to 379) in a potential 2B-like (2BL) region (amino acids 301 to 398) near the C terminus of the Norwalk virus N-terminal protein reduced Golgi colocalization and disassembly. Confocal imaging was conducted to examine the expression characteristics of fusion proteins in which the 2BL region from the N-terminal protein of Norwalk virus (a genogroup I norovirus) or MD145 (a genogroup II norovirus) was fused to the C terminus of enhanced green fluorescent protein. Expression of each fusion protein in cells showed evidence for its colocalization with the Golgi apparatus. These data indicate that the N-terminal protein of Norwalk virus interacts with the Golgi apparatus and may play a 2BL role in the induction of intracellular membrane rearrangements associated with positive-strand RNA virus replication in cells.",,"['Fernandez-Vega, Virneliz', 'Sosnovtsev, Stanislav V.', 'Belliot, Gaël', 'King, Adriene D.', 'Mitra, Tanaji', 'Gorbalenya, Alexander', 'Green, Kim Y.']",,,,
,PMC,Abstracts / Résumés,,PMC2726570,,,,,,,,,
,PMC,Child injury prevention in Canada: Where we stand,,PMC2721179,,,,,"Pless, Barry",,,,
,PMC,tRNA slippage at the tmRNA resume codon,http://dx.doi.org/10.1261/rna.7010904,PMC1370571,,,"The bacterial ribosome does not initiate translation on the mRNA portion of tmRNA; instead translation that had begun on a separate mRNA molecule resumes at a particular triplet on tmRNA (the resume codon). For at least two tRNAs that could pair with both the resume and −2 triplets on mutant tmRNAs, UAA (stop) as the second codon induced high-frequency −2 slippage on the resume codon in the P site. The frameshift product was not detected when the −2 base was altered. Deficiency for ribosomal L9 protein, which affects other cases of frameshifting, had no significant effect. A special feature of this frameshifting is its dependence on a particular context, that of the tmRNA resume codon; it failed on the same sequence in a regular mRNA, and, more strikingly, at the second tmRNA codon. This focuses attention on the peculiar features expected of the slippage-prone state, such as unusual E-site filling, that might make the P-site resume codon:anticodon interaction especially unstable. Keywords: tmRNA; ribosome; frameshift; E site; translation",,"['TRIMBLE, MICHAEL J.', 'MINNICUS, AMY', 'WILLIAMS, KELLY P.']",,,,
,PMC,2004 update of BTS pneumonia guidelines: what's new?,http://dx.doi.org/10.1136/thx.2004.024992,PMC1747016,,,,,"['Macfarlane, J', 'Boldy, D']",,,,
,PMC,Chronic occupational exposure to nitrogen dioxide is associated with decline in lung function,http://dx.doi.org/10.1136/thx.2004.la0088,PMC1747012,,,,,"Johns, R",,,,
,PMC,α(1)-Antitrypsin: more than just deficiency,http://dx.doi.org/10.1136/thx.2004.023572,PMC1747011,,,,,"Stockley, R",,,,
,PMC,Severe acute respiratory syndrome: report of treatment and outcome after a major outbreak,http://dx.doi.org/10.1136/thx.2003.014076,PMC1746995,,,"Background: The outcome is reported of a prospective uncontrolled study based on a stepwise treatment protocol during an outbreak of severe acute respiratory syndrome (SARS) in Hong Kong. Method: One hundred and thirty eight patients were treated with broad spectrum antibiotics, a combination of ribavirin and low dose corticosteroid, and then intravenous high dose methylprednisolone according to responses. Sustained response to treatment was defined as (1) defervescence for ⩾4 consecutive days, (2) resolution of lung consolidation by >25%, and (3) oxygen independence by the fourth day without fever. Patients with defervescence who achieved either criterion 2 or 3 were classified as partial responders. Patients who fell short of criteria 2 and 3 were non-responders. Results: Laboratory confirmation of SARS coronavirus infection was established in 132 (95.7%). None responded to antibiotics but 25 (18.1%) responded to ribavirin + low dose corticosteroid. Methylprednisolone was used in 107 patients, of whom 95 (88.8%) responded favourably. Evidence of haemolytic anaemia was observed in 49 (36%). A high level of C-reactive protein at presentation was the only independent predictor for use of methylprednisolone (odds ratio 2.18 per 10 mg/dl increase, 95% confidence interval 1.12 to 4.25, p = 0.02). Thirty seven patients (26.8%) required admission to the intensive care unit and 21 (15.2%) required invasive mechanical ventilation. There were 15 deaths (mortality rate 10.9%), most with significant co-morbidities, whereas 122 (88.4%) had been discharged home 4 months after the outbreak onset. Conclusion: The use of high dose pulse methylprednisolone during the clinical course of a SARS outbreak was associated with clinical improvement, but randomised controlled trials are needed to ascertain its efficacy in this condition.",,"['Sung, J', 'Wu, A', 'Joynt, G', 'Yuen, K', 'Lee, N', 'Chan, P', 'Cockram, C', 'Ahuja, A', 'Yu, L', 'Wong, V', 'Hui, D']",,,,
,PMC,,,PMC404520,,,,,,,,,
,PMC,In brief,,PMC404486,,,,,,,,,
,PMC,Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice,http://dx.doi.org/10.1073/pnas.0401939101,PMC404098,,,"The spike protein (S), a membrane component of severe acute respiratory syndrome coronavirus (SARS-CoV) is anticipated to be an important component of candidate vaccines. We constructed recombinant forms of the highly attenuated modified vaccinia virus Ankara (MVA) containing the gene encoding full-length SARS-CoV S with and without a C-terminal epitope tag called MVA/S-HA and MVA/S, respectively. Cells infected with MVA/Sor MVA/S-HA synthesized a 200-kDa protein, which was recognized by antibody raised against a synthetic peptide of SARS-CoV S or the epitope tag in Western blot analyses. Further studies indicated that S was N-glycosylated and migrated in SDS polyacrylamide gels with an apparent mass of ≈160 kDa after treatment with peptide N-glycosidase F. The acquisition of resistance to endoglycosidase H indicated trafficking of S to the medial Golgi compartment, and confocal microscopy showed that S was transported to the cell surface. Intranasal or intramuscular inoculations of BALB/c mice with MVA/S produced serum antibodies that recognized the SARS S in ELISA and neutralized SARS-CoV in vitro. Moreover, MVA/S administered by either route elicited protective immunity, as shown by reduced titers of SARS-CoV in the upper and lower respiratory tracts of mice after challenge. Passive transfer of serum from mice immunized with MVA/S to naïve mice also reduced the replication of SARS-CoV in the respiratory tract after challenge, demonstrating a role for antibody to S in protection. The attenuated nature of MVA and the ability of MVA/S to induce neutralizing antibody that protects mice support further development of this candidate vaccine.",,"['Bisht, Himani', 'Roberts, Anjeanette', 'Vogel, Leatrice', 'Bukreyev, Alexander', 'Collins, Peter L.', 'Murphy, Brian R.', 'Subbarao, Kanta', 'Moss, Bernard']",,,,
,PMC,Role of protein kinase R in double-stranded RNA-induced expression of nitric oxide synthase in human astroglia,http://dx.doi.org/10.1016/S0014-5793(04)00302-3,PMC1986658,,,"Environmental factor(s), such as viral infection, has been implicated as one of the triggering events leading to neuroinflammation in multiple sclerosis. This study underlines the importance of double-stranded RNA (dsRNA), the active component of a viral infection, in inducing the expression of inducible nitric oxide synthase (iNOS) in human astroglia. DsRNA in the form of synthetic polyinosinic-polycytidylic acid (poly IC) induced expression of iNOS and iNOS promoter-driven luciferase activity through activation of nuclear factor (NF)-κB and CCAAT/enhancer-binding proteinβ (C/EBPβ). In addition, we show that inhibitors of protein kinase R attenuated iNOS by suppressing the activation of NF-κB but not C/EBPβ. In contrast, knock down of p38 mitogen-activated protein kinase (MAPK) attenuated iNOS by suppressing the activation of C/EBPβ but not NF-κB. This study delineates a novel role of dsRNA in inducing the expression of iNOS through dsRNA-activated protein kinase (PKR)-mediated activation of NF-κB and p38-mediated activation of C/EBPβ in human astroglia that may participate in virus-induced neurological abnormalities.",,"['Auch, Corey J.', 'Saha, Ramendra N.', 'Sheikh, Faruk G.', 'Liu, Xiaojuan', 'Jacobs, Bertram L.', 'Pahan, Kalipada']",,,,
,PMC,A previously undescribed coronavirus associated with respiratory disease in humans,http://dx.doi.org/10.1073/pnas.0400762101,PMC395948,,,"The etiology of acute respiratory tract illnesses is sometimes unclear due to limitations of diagnostic tests or the existence of as-yet-unidentified pathogens. Here we describe the identification and characterization of a not previously recognized coronavirus obtained from an 8-mo-old boy suffering from pneumonia. This coronavirus replicated efficiently in tertiary monkey kidney cells and Vero cells, in contrast to human coronaviruses (HCoV) 229E and OC43. The entire cDNA genome sequence of the previously undescribed coronavirus was determined, revealing that it is most closely related to porcine epidemic diarrhea virus and HCoV 229E. The maximum amino acid sequence identity between ORFs of the newly discovered coronavirus and related group 1 coronaviruses ranged from 43% to 67%. Real-time RT-PCR assays were designed to test for the prevalence of the previously undescribed coronavirus in humans. Using these tests, the virus was detected in four of 139 individuals (3%) who were suffering from respiratory illness with unknown etiology. All four patients suffered from fever, runny nose, and dry cough, and all four had underlying or additional morbidity. Our data will enable the development of diagnostic tests to study the prevalence and clinical impact of this virus in humans in more detail. Moreover, it will be important to discriminate this previously undescribed coronavirus from HCoV 229E and OC43 and the severe acute respiratory syndrome coronavirus.",,"['Fouchier, Ron A. M.', 'Hartwig, Nico G.', 'Bestebroer, Theo M.', 'Niemeyer, Berend', 'de Jong, Jan C.', 'Simon, James H.', 'Osterhaus, Albert D. M. E.']",,,,
,PMC,Factors that make an infectious disease outbreak controllable,http://dx.doi.org/10.1073/pnas.0307506101,PMC395937,,,"The aim of this study is to identify general properties of emerging infectious agents that determine the likely success of two simple public health measures in controlling outbreaks, namely (i) isolating symptomatic individuals and (ii) tracing and quarantining their contacts. Because these measures depend on the recognition of specific disease symptoms, we investigate the relative timing of infectiousness and the appearance of symptoms by using a mathematical model. We show that the success of these control measures is determined as much by the proportion of transmission occurring prior to the onset of overt clinical symptoms (or via asymptomatic infection) as the inherent transmissibility of the etiological agent (measured by the reproductive number R(0)). From published studies, we estimate these quantities for two moderately transmissible viruses, severe acute respiratory syndrome coronavirus and HIV, and for two highly transmissible viruses, smallpox and pandemic influenza. We conclude that severe acute respiratory syndrome and smallpox are easier to control using these simple public health measures. Direct estimation of the proportion of asymptomatic and presymptomatic infections is achievable by contact tracing and should be a priority during an outbreak of a novel infectious agent.",,"['Fraser, Christophe', 'Riley, Steven', 'Anderson, Roy M.', 'Ferguson, Neil M.']",,,,
,PMC,Canadian doctors welcome public health initiatives in wake of SARS,,PMC383399,,,,,"Kermode-Scott, Barbara",,,,
,PMC,Burden of infectious diseases in South Asia,,PMC383379,,,"Infectious diseases are a major cause of death in South Asia, with children incurring a disproportionate share of the burden. This review discusses the underlying causes of some of the more common diseases and strategies to improve their detection and control",,"['Zaidi, Anita K M', 'Awasthi, Shally', 'deSilva, H Janaka']",,,,
,PMC,The Impact of the SARS Epidemic on the Utilization of Medical Services: SARS and the Fear of SARS,,PMC1448298,,,"Using interrupted time-series analysis and National Health Insurance data between January 2000 and August 2003, this study assessed the impacts of the severe acute respiratory syndrome (SARS) epidemic on medical service utilization in Taiwan. At the peak of the SARS epidemic, significant reductions in ambulatory care (23.9%), inpatient care (35.2%), and dental care (16.7%) were observed. People’s fears of SARS appear to have had strong impacts on access to care. Adverse health outcomes resulting from accessibility barriers posed by the fear of SARS should not be overlooked.",,"['Chang, Hong-Jen', 'Huang, Nicole', 'Lee, Cheng-Hua', 'Hsu, Yea-Jen', 'Hsieh, Chi-Jeng', 'Chou, Yiing-Jenq']",,,,
,PMC,Injury Prevention Research at the Centers for Disease Control and Prevention,,PMC1448287,,,,,"['Doll, Lynda', 'Binder, Sue']",,,,
,PMC,Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome,http://dx.doi.org/10.1111/j.1365-2249.2004.02415.x,PMC1808997,,,"Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel coronavirus, but its immunopathological mechanisms have not yet been fully elucidated. We investigated changes in plasma T helper (Th) cell cytokines, inflammatory cytokines and chemokines in 20 patients diagnosed with SARS. Cytokine profile of SARS patients showed marked elevation of Th1 cytokine interferon (IFN)-γ, inflammatory cytokines interleukin (IL)-1, IL-6 and IL-12 for at least 2 weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumour necrosis factor (TNF)-α, anti-inflammatory cytokine IL-10, Th1 cytokine IL-2 and Th2 cytokine IL-4. The chemokine profile demonstrated significant elevation of neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-γ-inducible protein-10 (IP-10). Corticosteroid reduced significantly IL-8, MCP-1 and IP-10 concentrations from 5 to 8 days after treatment (all P < 0·001). Together, the elevation of Th1 cytokine IFN-γ, inflammatory cytokines IL-1, IL-6 and IL-12 and chemokines IL-8, MCP-1 and IP-10 confirmed the activation of Th1 cell-mediated immunity and hyperinnate inflammatory response in SARS through the accumulation of monocytes/macrophages and neutrophils.",,"['WONG, C K', 'LAM, C W K', 'WU, A K L', 'IP, W K', 'LEE, N L S', 'CHAN, I H S', 'LIT, L C W', 'HUI, D S C', 'CHAN, M H M', 'CHUNG, S S C', 'SUNG, J J Y']",,,,
,PMC,What does the peripheral blood tell you in SARS?,http://dx.doi.org/10.1111/j.1365-2249.2004.02448.x,PMC1808995,,,,,"OPENSHAW, P J M",,,,
,PMC,Immunological Characterization of the Spike Protein of the Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JCM.42.4.1570-1576.2004,PMC387621,,,"Severe acute respiratory syndrome (SARS) is a novel infectious disease caused by the SARS-associated coronavirus (SARS-CoV). There are four major structural proteins in the SARS-CoV, including the nucleocapsid, spike, membrane, and small envelope proteins. In this study, two sets of truncated fragments of spike protein were generated, the first were approximately 210-bp nonoverlapping fragments and the second were overlapping segments of 750 to 900 bp. From these 23 fragments, we identified a fragment of 259 amino acids (amino acids 441 to 700) that is a major immunodominant epitope. This fragment was highly expressed, and the purified fragment C could detect all 33 SARS patient serum samples tested, collected from 7 to 60 days after the onset of fever, but had no reactivity with all 66 healthy human serum samples tested. Thus, fragment C of spike protein was identified as an immunodominant antigen and could be used for serological detection of SARS-CoV infection.",,"['Lu, Liqun', 'Manopo, Ivanus', 'Leung, Bernard P.', 'Chng, Hiok Hee', 'Ling, Ai Ee', 'Chee, Li Lian', 'Ooi, Eng Eong', 'Chan, Shzu-Wei', 'Kwang, Jimmy']",,,,
,PMC,SYBR Green-Based Real-Time Quantitative PCR Assay for Detection of West Nile Virus Circumvents False-Negative Results Due to Strain Variability,http://dx.doi.org/10.1128/JCM.42.4.1511-1518.2004,PMC387603,,,"Real-time quantitative PCR is used routinely for the high-throughput diagnosis of viral pathogens, such as West Nile virus (WNV). Rapidly evolving RNA viruses present a challenge for diagnosis because they accumulate mutations that may render them undetectable. To explore the effect of sequence variations on assay performance, we generated every possible single point mutation within the target region of the widely used TaqMan assay for WNV and found that the TaqMan assay failed to detect 47% of possible single nucleotide variations in the probe-binding site and was unable to detect any targets with more than two mutations. In response, we developed and validated a less expensive assay with the intercalating dye SYBR green. The SYBR green-based assay was as sensitive as the TaqMan assay for WNV. Importantly, it detected 100% of possible WNV target region variants. The assay developed here adds an additional layer of protection to guard against false-negative results that result from natural variations or drug-directed selection and provides a rapid means to identify such variants for subsequent detailed analysis.",,"['Papin, James F.', 'Vahrson, Wolfgang', 'Dittmer, Dirk P.']",,,,
,PMC,Performance and Cost Evaluation of One Commercial and Six In-House Conventional and Real-Time Reverse Transcription-PCR Assays for Detection of Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JCM.42.4.1471-1476.2004,PMC387602,,,"We evaluated seven reverse transcription-PCR (RT-PCR) assays, including six in-house assays and one commercial assay for the detection of severe acute respiratory syndrome coronavirus (SARS-CoV) RNA in clinical specimens. RT-PCR assays targeted different genomic regions and included three conventional assays (one nested and two non-nested) run on a conventional heat block and four real-time assays performed in a LightCycler (LC; Roche Diagnostics). All in-house assays were optimized for assay parameters, including MgCl(2), primer, and probe concentrations. The commercial assay was the RealArt HPA CoV RT-PCR assay (Artus), which was run in the LC. Testing serial dilutions of cultured SARS-CoV showed that the analytical sensitivity of the assays ranged from 10(−8) to 10(−6), corresponding to 1 and 100 copies of viral RNA, respectively. Significant differences in analytical sensitivities were observed between assays (P < 0.01, probit regression analysis for 50% sensitivity levels for the top two assays versus the others). Testing 68 clinical specimens (including 17 respiratory tract specimens, 29 urine samples, and 22 stools or rectal swabs) demonstrated that six of the seven assays detected at least 17 of 18 positives (defined as positive in at least two assays), and two of the assays had a sensitivity of 100%. There were no significant differences in sensitivity between the assays (P = 0.5 [Cochrance Q test, least sensitive 15 of 18 versus 18 of 18]). The specificities of the assays ranged from 94.0 to 100% without significant differences (P = 0.25 to 0.5 [McNemar test]). The reagent and technologist cost of performing the in-house PCR assays ranged from $5.46 to $9.81 Canadian dollars (CDN) per test. The commercial assay cost was considerably higher at $40.37 per test. The results demonstrated good performance for all assays, providing laboratories that need to do SARS RNA testing with a choice of assay formats.",,"['Mahony, James B.', 'Petrich, Astrid', 'Louie, Lisa', 'Song, Xinyu', 'Chong, Sylvia', 'Smieja, Marek', 'Chernesky, Max', 'Loeb, Mark', 'Richardson, Susan', None]",,,,
,PMC,"Rapid and Sensitive Method Using Multiplex Real-Time PCR for Diagnosis of Infections by Influenza A and Influenza B Viruses, Respiratory Syncytial Virus, and Parainfluenza Viruses 1, 2, 3, and 4",http://dx.doi.org/10.1128/JCM.42.4.1564-1569.2004,PMC387552,,,"Laboratory diagnosis of viral respiratory infections is generally performed by virus isolation in cell culture and immunofluorescent assays. Reverse transcriptase PCR is now recognized as a sensitive and specific alternative for detection of respiratory RNA viruses. A rapid real-time multiplex PCR assay was developed for the detection of influenza A and influenza B viruses, human respiratory syncytial virus (RSV), parainfluenza virus 1 (PIV1), PIV2, PIV3, and PIV4 in a two-tube multiplex reaction which used molecular beacons to discriminate the pathogens. A total of 358 respiratory samples taken over a 1-year period were analyzed by the multiplex assay. The incidence of respiratory viruses detected in these samples was 67 of 358 (19%) and 87 of 358 (24%) by culture and real-time PCR, respectively. Culture detected 3 influenza A virus, 2 influenza B virus, 57 RSV, 2 PIV1, and 2 PIV3 infections. All of these culture-positive samples and an additional 5 influenza A virus, 6 RSV, 2 PIV1, 1 PIV2, 1 PIV3, and 3 PIV4 infections were detected by the multiplex real-time PCR. The application of real-time PCR to clinical samples increases the sensitivity for respiratory viral diagnosis. In addition, results can be obtained within 6 h, which increases clinical relevance. Therefore, use of this real-time PCR assay would improve patient management and infection control.",,"['Templeton, Kate E.', 'Scheltinga, Sitha A.', 'Beersma, Matthias F. C.', 'Kroes, Aloys C. M.', 'Claas, Eric C. J.']",,,,
,PMC,Molecular Diagnosis of Human Adenoviruses D and E by a Phylogeny-Based Classification Method Using a Partial Hexon Sequence,http://dx.doi.org/10.1128/JCM.42.4.1577-1584.2004,PMC387551,,,"Human adenoviruses (HAdVs) are the major causes of a variety of acute illnesses. Virus isolation and neutralization tests are usually done to identify the causative virus, but these tests are labor-intensive and time-consuming, and standardized antisera are in limited supply. This study investigated a rapid and reliable method of virus identification based on PCR and phylogenetic analysis. The phylogenetic tree constructed by neighbor joining on the basis of the newly determined partial hexon sequences from 33 prototypes of HAdV-D and -E, along with 11 available prototypes of HAdV-A to -C and -F from GenBank, allowed HAdVs to be grouped into six distinct clusters. These clusters correspond closely to the six newly designated species, HAdV-A to -F. The partial hexon sequences of 57 isolates from patients with acute conjunctivitis obtained over 20 years plus those of 44 prototype strains were analyzed. Each isolate formed a monophyletic cluster along with its respective prototype strain, allowing serotype identification. Partial-hexon-based classification appears to be an effective tool for studying the molecular epidemiology of HAdVs.",,"['Shimada, Yasushi', 'Ariga, Toshihide', 'Tagawa, Yoshitsugu', 'Aoki, Koki', 'Ohno, Shigeaki', 'Ishiko, Hiroaki']",,,,
,PMC,Two Genotypes of Canine Coronavirus Simultaneously Detected in the Fecal Samples of Dogs with Diarrhea,http://dx.doi.org/10.1128/JCM.42.4.1797-1799.2004,PMC387541,,,"Sixty-nine fecal samples from diarrheic puppies were examined by reverse transcription-PCR assays for the M and the S genes of canine coronaviruses (CCoVs). The isolates in 10 samples were recognized as CCoV type I, and the isolates in 6 samples were recognized as CCoV type II, while isolates of both genotypes were simultaneously detected in 53 samples.",,"['Pratelli, Annamaria', 'Decaro, Nicola', 'Tinelli, Antonella', 'Martella, Vito', 'Elia, Gabriella', 'Tempesta, Maria', 'Cirone, Francesco', 'Buonavoglia, Canio']",,,,
,PMC,What are the chances? Evaluating risk and benefit information in consumer health materials,,PMC385301,,,"Much consumer health information addresses issues of disease risk or treatment risks and benefits, addressing questions such as “How effective is this treatment?” or “What is the likelihood that this test will give a false positive result?” Insofar as it addresses outcome likelihood, this information is essentially quantitative in nature, which is of critical importance, because quantitative information tends to be difficult to understand and therefore inaccessible to consumers. Information professionals typically examine reading level to determine the accessibility of consumer health information, but this measure does not adequately reflect the difficulty of quantitative information, including materials addressing issues of risk and benefit. As a result, different methods must be used to evaluate this type of consumer health material. There are no standard guidelines or assessment tools for this task, but research in cognitive psychology provides insight into the best ways to present risk and benefit information to promote understanding and minimize interpretation bias. This paper offers an interdisciplinary bridge that brings these results to the attention of information professionals, who can then use them to evaluate consumer health materials addressing risks and benefits.",,"Burkell, Jacquelyn",,,,
,PMC,Development of Gastrointestinal Function: Risk Factors for Necrotizing Enterocolitis,http://dx.doi.org/10.5863/1551-6776-9.2.96,PMC3469134,,,"The intestinal tract of the fetus matures rapidly in the third trimester of the pregnancy. The premature infant has decreased intestinal motility, limited digestion, absorption and excretion, and poor intestinal barrier defense. These limitations place the infant at high risk for acute intestinal injury, necrotizing enterocolitis. This article reviews the development of the gastrointestinal tract in the fetus, the barriers to feeding the high risk, premature infant, and the most serious intestinal disease, necrotizing enterocolitis.",,"['Clark, David A.', 'Mitchell, Amy L.']",,,,
,PMC,Rapid Diagnosis of Ebola Hemorrhagic Fever by Reverse Transcription-PCR in an Outbreak Setting and Assessment of Patient Viral Load as a Predictor of Outcome,http://dx.doi.org/10.1128/JVI.78.8.4330-4341.2004,PMC374287,,,"The largest outbreak on record of Ebola hemorrhagic fever (EHF) occurred in Uganda from August 2000 to January 2001. The outbreak was centered in the Gulu district of northern Uganda, with secondary transmission to other districts. After the initial diagnosis of Sudan ebolavirus by the National Institute for Virology in Johannesburg, South Africa, a temporary diagnostic laboratory was established within the Gulu district at St. Mary's Lacor Hospital. The laboratory used antigen capture and reverse transcription-PCR (RT-PCR) to diagnose Sudan ebolavirus infection in suspect patients. The RT-PCR and antigen-capture diagnostic assays proved very effective for detecting ebolavirus in patient serum, plasma, and whole blood. In samples collected very early in the course of infection, the RT-PCR assay could detect ebolavirus 24 to 48 h prior to detection by antigen capture. More than 1,000 blood samples were collected, with multiple samples obtained from many patients throughout the course of infection. Real-time quantitative RT-PCR was used to determine the viral load in multiple samples from patients with fatal and nonfatal cases, and these data were correlated with the disease outcome. RNA copy levels in patients who died averaged 2 log(10) higher than those in patients who survived. Using clinical material from multiple EHF patients, we sequenced the variable region of the glycoprotein. This Sudan ebolavirus strain was not derived from either the earlier Boniface (1976) or Maleo (1979) strain, but it shares a common ancestor with both. Furthermore, both sequence and epidemiologic data are consistent with the outbreak having originated from a single introduction into the human population.",,"['Towner, Jonathan S.', 'Rollin, Pierre E.', 'Bausch, Daniel G.', 'Sanchez, Anthony', 'Crary, Sharon M.', 'Vincent, Martin', 'Lee, William F.', 'Spiropoulou, Christina F.', 'Ksiazek, Thomas G.', 'Lukwiya, Mathew', 'Kaducu, Felix', 'Downing, Robert', 'Nichol, Stuart T.']",,,,
,PMC,"Live, Attenuated Coronavirus Vaccines through the Directed Deletion of Group-Specific Genes Provide Protection against Feline Infectious Peritonitis",http://dx.doi.org/10.1128/JVI.78.8.3863-3871.2004,PMC374255,,,"Feline infectious peritonitis (FIP) is a fatal immunity-mediated disease caused by mutants of a ubiquitous coronavirus. Since previous attempts to protect cats under laboratory and field conditions have been largely unsuccessful, we used our recently developed system of reverse genetics (B. J. Haijema, H. Volders, and P. J. M. Rottier, J. Virol. 77:4528-4538, 2003) for the development of a modified live FIP vaccine. With this objective, we deleted the group-specific gene cluster open reading frame 3abc or 7ab and obtained deletion mutant viruses that not only multiplied well in cell culture but also showed an attenuated phenotype in the cat. At doses at which the wild-type virus would be fatal, the mutants with gene deletions did not cause any clinical symptoms. They still induced an immune response, however, as judged from the high levels of virus-neutralizing antibodies. The FIP virus (FIPV) mutant lacking the 3abc cluster and, to a lesser extent, the mutant missing the 7ab cluster, protected cats against a lethal homologous challenge; no protection was obtained with the mutant devoid of both gene clusters. Our studies show that the deletion of group-specific genes from the coronavirus genome results in live attenuated candidate vaccines against FIPV. More generally, our approach may allow the development of vaccines against infections with other pathogenic coronaviruses, including that causing severe acute respiratory syndrome in humans.",,"['Haijema, Bert Jan', 'Volders, Haukeline', 'Rottier, Peter J. M.']",,,,
,PMC,Prior Infection and Passive Transfer of Neutralizing Antibody Prevent Replication of Severe Acute Respiratory Syndrome Coronavirus in the Respiratory Tract of Mice,http://dx.doi.org/10.1128/JVI.78.7.3572-3577.2004,PMC371090,,,"Following intranasal administration, the severe acute respiratory syndrome (SARS) coronavirus replicated to high titers in the respiratory tracts of BALB/c mice. Peak replication was seen in the absence of disease on day 1 or 2, depending on the dose administered, and the virus was cleared within a week. Viral antigen and nucleic acid were detected in bronchiolar epithelial cells during peak viral replication. Mice developed a neutralizing antibody response and were protected from reinfection 28 days following primary infection. Passive transfer of immune serum to naïve mice prevented virus replication in the lower respiratory tract following intranasal challenge. Thus, antibodies, acting alone, can prevent replication of the SARS coronavirus in the lung, a promising observation for the development of vaccines, immunotherapy, and immunoprophylaxis regimens.",,"['Subbarao, Kanta', 'McAuliffe, Josephine', 'Vogel, Leatrice', 'Fahle, Gary', 'Fischer, Steven', 'Tatti, Kathleen', 'Packard, Michelle', 'Shieh, Wun-Ju', 'Zaki, Sherif', 'Murphy, Brian']",,,,
,PMC,Coronavirus Neurovirulence Correlates with the Ability of the Virus To Induce Proinflammatory Cytokine Signals from Astrocytes and Microglia,http://dx.doi.org/10.1128/JVI.78.7.3398-3406.2004,PMC371061,,,"The molecular and cellular basis of coronavirus neurovirulence is poorly understood. Since neurovirulence may be determined at the early stages of infection of the central nervous system (CNS), we hypothesize that it may depend on the ability of the virus to induce proinflammatory signals from brain cells for the recruitment of blood-derived inflammatory cells. To test this hypothesis, we studied the interaction between coronaviruses (mouse hepatitis virus) of different neurovirulences with primary cell cultures of brain immune cells (astrocytes and microglia) and mouse tissues. We found that the level of neurovirulence of the virus correlates with its differential ability to induce proinflammatory cytokines (interleukin 12 [IL-12] p40, tumor necrosis factor alpha, IL-6, IL-15, and IL-1β) in astrocytes and microglia and in mouse brains and spinal cords. These findings suggest that coronavirus neurovirulence may depend on a novel discriminatory ability of astrocytes and microglia to induce a proinflammatory response in the CNS.",,"['Li, Yun', 'Fu, Li', 'Gonzales, Donna M.', 'Lavi, Ehud']",,,,
,PMC,SARS virus returns to China as scientists race to find effective vaccine.,,PMC2585904,,,,,"Fleck, Fiona",,,,
,PMC,SARS and the removal of personal protective equipment,http://dx.doi.org/10.1503/cmaj.1031700,PMC359412,,,,,"['Puro, Vincenzo', 'Nicastri, Emanuele']",,,,
,PMC,Mild SARS in elderly patients,http://dx.doi.org/10.1503/cmaj.1031734,PMC359408,,,,,"['Cheng, Hing Ming', 'Kwok, Timothy']",,,,
,PMC,Emerging infectious diseases,http://dx.doi.org/10.1172/JCI200421370,PMC362132,,,"Human population growth, technological advances, and changing social behaviors lead to the selection of new microbial pathogens. Antimicrobial drugs, vaccines, diagnostics, and treatments for emerging infectious diseases must be developed. The selective forces that drive the emergence of new infectious diseases, and the implications for our survival, are just beginning to be understood.",,"Racaniello, Vincent R.",,,,
,PMC,"Germs, governance, and global public health in the wake of SARS",http://dx.doi.org/10.1172/JCI200421328,PMC362129,,,"A revolution in the governance of global infectious disease threats is under way, accelerated by events triggered by the outbreak of SARS in 2003. This review article analyzes pre-SARS trends in the governance of infectious diseases, examines the impact of the SARS outbreak on these trends, and posits that germ governance is now a criterion of “good governance” in world affairs.",,"Fidler, David P.",,,,
,PMC,Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry,http://dx.doi.org/10.1073/pnas.0306446101,PMC384725,,,"Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is a rapidly emerging pathogen with potentially serious consequences for public health. Here we describe conditions that result not only in the efficient expression of the SARS-CoV spike (S) protein on the surface of cells, but in its incorporation into lentiviral particles that can be used to transduce cells in an S glycoprotein-dependent manner. We found that although some primate cell lines, including Vero E6, 293T and Huh-7 cells, could be efficiently transduced by SARS-CoV S glycoprotein pseudoviruses, other cells lines were either resistant or very poorly permissive to virus entry. Infection by pseudovirions could be inhibited by several lysosomotropic agents, suggesting a requirement for acidification of endosomes for efficient S-mediated viral entry. In addition, we were able to develop a cell–cell fusion assay that could be used to monitor S glycoprotein-dependent membrane fusion. Although proteolysis did not enhance the infectivity of cell-free pseudovirions, trypsin activation is required for cell–cell fusion. Additionally, there was no apparent pH requirement for S glycoprotein-mediated cell–cell fusion. Together, these studies describe important tools that can be used to study SARS-CoV S glycoprotein structure and function, including approaches that can be used to identify inhibitors of the entry of SARS-CoV into target cells.",,"['Simmons, Graham', 'Reeves, Jacqueline D.', 'Rennekamp, Andrew J.', 'Amberg, Sean M.', 'Piefer, Andrew J.', 'Bates, Paul']",,,,
,PMC,The severe acute respiratory syndrome-coronavirus replicative protein nsp9 is a single-stranded RNA-binding subunit unique in the RNA virus world,http://dx.doi.org/10.1073/pnas.0307877101,PMC374323,,,"The recently identified etiological agent of the severe acute respiratory syndrome (SARS) belongs to Coronaviridae (CoV), a family of viruses replicating by a poorly understood mechanism. Here, we report the crystal structure at 2.7-Å resolution of nsp9, a hitherto uncharacterized subunit of the SARS-CoV replicative polyproteins. We show that SARS-CoV nsp9 is a single-stranded RNA-binding protein displaying a previously unreported, oligosaccharide/oligonucleotide fold-like fold. The presence of this type of protein has not been detected in the replicative complexes of RNA viruses, and its presence may reflect the unique and complex CoV viral replication/transcription machinery.",,"['Egloff, Marie-Pierre', 'Ferron, François', 'Campanacci, Valérie', 'Longhi, Sonia', 'Rancurel, Corinne', 'Dutartre, Hélène', 'Snijder, Eric J.', 'Gorbalenya, Alexander E.', 'Cambillau, Christian', 'Canard, Bruno']",,,,
,PMC,The Internet as a Vehicle to Communicate Health Information During a Public Health Emergency: A Survey Analysis Involving the Anthrax Scare of 2001,http://dx.doi.org/10.2196/jmir.6.1.e8,PMC1550585,15111274,CC BY,"BACKGROUND: The recent public health risks arising from bioterrorist threats and outbreaks of infectious diseases like SARS (Severe Acute Respiratory Syndrome) highlight the challenges of effectively communicating accurate health information to an alarmed public. OBJECTIVE: To evaluate use of the Internet in accessing information related to the anthrax scare in the United States in late 2001, and to strategize about the most effective use of this technology as a communication vehicle during times of public health crises. METHODS: A paper-based survey to assess how individuals obtained health information relating to bioterrorism and anthrax during late 2001.We surveyed 500 randomly selected patients from two ambulatory primary care clinics affiliated with the Brigham and Women's Hospital in Boston, Massachusetts. RESULTS: The response rate was 42%. While traditional media provided the primary source of information on anthrax and bioterrorism, 21% (95% CI, 15% - 27%) of respondents reported searching the Internet for this information during late 2001. Respondents reported trusting information from physicians the most, and information from health websites slightly more than information from any traditional media source. Over half of those searching the Internet reported changing their behavior as a result of information found online. CONCLUSIONS: Many people already look to the Internet for information during a public health crisis, and information found online can positively influence behavioral responses to such crises. However, the potential of the Internet to convey accurate health information and advice has not yet been realized. In order to enhance the effectiveness of public-health communication, physician practices could use this technology to pro-actively e-mail their patients validated information. Still, unless Internet access becomes more broadly available, its benefits will not accrue to disadvantaged populations.",2004 Mar 3,"['Kittler, Anne F', 'Hobbs, John', 'Volk, Lynn A', 'Kreps, Gary L', 'Bates, David W']",J Med Internet Res,,,
,PMC,The psychological impact of SARS: a matter of heart and mind,http://dx.doi.org/10.1503/cmaj.1032003,PMC343855,,,,,"['Sim, Kang', 'Chua, Hong Choon']",,,,
,PMC,Psychosocial effects of SARS on hospital staff: survey of a large tertiary care institution,http://dx.doi.org/10.1503/cmaj.1031077,PMC343853,,,"BACKGROUND: The outbreak of SARS in 2003 had a dramatic effect on the health care system in Toronto. The main objective of this study was to investigate the psychosocial effects associated with working in a hospital environment during this outbreak. METHODS: Questionnaires were distributed to all willing employees of Sunnybrook and Women's College Health Sciences Centre between Apr. 10 and 22, 2003. The survey included questions regarding concern about SARS, precautionary measures, personal well-being and sociodemographic characteristics; a subsample also received the 12-item version of the General Health Questionnaire (GHQ-12). RESULTS: Of the 4283 questionnaires distributed, 2001 (47%) were returned, representing 27% of the total hospital employee population of 7474. The proportions of respondents who were allied health care professionals, nurses and doctors and who worked in areas other than patient care were representative of the hospital staff population as a whole. Of the 2001 questionnaires, 510 contained the GHQ-12. Two-thirds of the respondents reported SARS-related concern for their own or their family's health. A total of 148 respondents (29%) scored above the threshold point on the GHQ-12, indicating probable emotional distress; the rate among nurses was 45%. Masks were reported to be the most bothersome infection control precaution. Logistic regression analysis identified 4 factors as being significantly associated with increased levels of concern for personal or family health: perception of a greater risk of death from SARS (adjusted odds ratio [OR] 5.0, 95% confidence interval [CI] 2.6–9.6), living with children (adjusted OR 1.8, 95% CI 1.5–2.3), personal or family lifestyle affected by SARS outbreak (adjusted OR 3.3, 95% CI 2.5–4.3) and being treated differently by people because of working in a hospital (adjusted OR 1.6, 95% CI 1.2–2.1). Four factors were identified as being significantly associated with the presence of emotional distress: being a nurse (adjusted OR 2.8, 95% CI 1.5–5.5), part-time employment status (adjusted OR 2.6, 95% CI 1.2–5.4), lifestyle affected by SARS outbreak (adjusted OR 2.2, 95% CI 1.4–3.5) and ability to do one's job affected by the precautionary measures (adjusted OR 2.9, 95% CI 1.9–4.6). INTERPRETATION: Our findings indicate that the SARS outbreak had significant psychosocial effects on hospital staff. These effects differed with respect to occupation and risk perception. The effect on families and lifestyle was also substantial. These findings highlight the need for interventions to address psychosocial distress and concern and to provide support for employees during such crises.",,"['Nickell, Leslie A.', 'Crighton, Eric J.', 'Tracy, C. Shawn', 'Al-Enazy, Hadi', 'Bolaji, Yemisi', 'Hanjrah, Sagina', 'Hussain, Ayesha', 'Makhlouf, Samia', 'Upshur, Ross E.G.']",,,,
,PMC,The high impact of an influenza pandemic,http://dx.doi.org/10.1503/cmaj.1040167,PMC343832,,,,,"Skowronski, Danuta",,,,
,PMC,When surgeons become SARS patients.,,PMC1964158,,,,,"['Wan, Innes Y. P.', 'Wan, Song', 'Arifi, Ahmed A.', 'Yim, Anthony P. C.']",,,,
,PMC,Pancreatic debridement in a district general hospital--viable or vulnerable?,,PMC1964155,,,,,"Ammori, Basil J.",,,,
,PMC,Referral guidelines for colorectal cancer--do they work?,http://dx.doi.org/10.1308/003588404322827581,PMC1964154,,,,,"['Adair, A.', 'Bennis, M.', 'Clifton, M. A.']",,,,
,PMC,Erosive adenomatosis of the nipple--a report of three cases.,,PMC1964152,,,,,"['Davies, G. L. S.', 'Sacks, N. P. M.', 'Gordon, A. B.', 'Trott, P. A.']",,,,
,PMC,"Geldanamycin, a Ligand of Heat Shock Protein 90, Inhibits the Replication of Herpes Simplex Virus Type 1 In Vitro",http://dx.doi.org/10.1128/AAC.48.3.867-872.2004,PMC353133,,,"Geldanamycin (GA) is an antibiotic targeting the ADP/ATP binding site of heat shock protein 90 (Hsp90). In screening for anti-herpes simplex virus type 1 (HSV-1) candidates, we found GA active against HSV-1. HSV-1 replication in vitro was significantly inhibited by GA with an 50% inhibitory concentration of 0.093 μM and a concentration that inhibited cellular growth 50% in comparison with the results seen with untreated controls of 350 μM. The therapeutic index of GA was over 3,700 (comparable to the results seen with acyclovir). GA did not inhibit HSV-1 thymidine kinase. Cells infected with HSV-1 demonstrated cell cycle arrest at the G(1)/S transition; however, treatment with GA resulted in a cell cycle distribution pattern identical to that of untreated cells, indicating a restoration of cell growth in HSV-1-infected cells by GA treatment. Accordingly, HSV-1 DNA synthesis was suppressed in HSV-1(+) cells treated with GA. The antiviral mechanism of GA appears to be associated with Hsp90 inactivation and cell cycle restoration, which indicates that GA exhibits broad-spectrum antiviral activity. Indeed, GA exhibited activities in vitro against other viruses, including severe acute respiratory syndrome coronavirus. Since GA inhibits HSV-1 through a cellular mechanism unique among HSV-1 agents, we consider it a new candidate agent for HSV-1.",,"['Li, Yu-Huan', 'Tao, Pei-Zhen', 'Liu, Yu-Zhen', 'Jiang, Jian-Dong']",,,,
,PMC,Shaping the future of global health.,,PMC2572381,,,,,"Haines, Andy",,,,
,PMC,Transfusion and risk of infection in Canada: UPDATE 2004,,PMC2094962,,,,,,,,,
,PMC,"Immunohistochemical study of Hemophilus somnus, Mycoplasma bovis, Mannheimia hemolytica, and bovine viral diarrhea virus in death losses due to myocarditis in feedlot cattle",,PMC548609,,,"The purpose of this study was to determine the presence of Hemophilus somnus, Mycoplasma bovis, Mannheimia hemolytica, and bovine viral diarrhea virus (BVDV) in lesional tissues of feeder calves dying with myocarditis. Tissues from the heart and lungs of 92 calves dying with myocarditis in Alberta feedlots were immunohistochemically stained for the antigens of these agents. Tissues from 44 calves dying from noninfectious causes and 35 calves dying with pneumonia were tested as controls. Hemophilus somnus was found in cardiac lesions in the majority of myocarditis cases (70/92). Mycoplasma bovis was concurrently demonstrated in the hearts of 4/92 affected calves. No bacterial pathogens were found in heart tissues from the control groups of calves. Bovine viral diarrhea virus was demonstrated in the tissues of 4/92 myocarditis cases compared with those of 13/35 calves dying from pneumonia and 0/44 calves dying from noninfectious causes. The results demonstrate that H. somnus is the principle pathogen associated with myocarditis in feedlot calves and that the presence of BVDV is more common in these calves compared with calves dying of noninfectious causes. The findings also suggest that BVDV is an important pathogen in calves dying with gross postmortem lesions of pneumonia.",,"['Haines, Deborah M.', 'Moline, Karen M.', 'Sargent, Ron A.', 'Campbell, John R.', 'Myers, Douglas J.', 'Doig, Paul A.']",,,,
,PMC,Recombinant Protein-Based Enzyme-Linked Immunosorbent Assay and Immunochromatographic Tests for Detection of Immunoglobulin G Antibodies to Severe Acute Respiratory Syndrome (SARS) Coronavirus in SARS Patients,http://dx.doi.org/10.1128/CDLI.11.2.287-291.2004,PMC371224,,,"An enzyme-linked immunosorbent assay (ELISA) and a rapid immunochromatographic test for detection of immunoglobulin G (IgG) antibodies in severe acute respiratory syndrome (SARS) patients were developed by utilizing the well-characterized recombinant proteins Gst-N and Gst-U274. The ELISA detected IgG antibodies to SARS-CoV in all 74 convalescent-phase samples from SARS patients while weakly cross-reacting to only 1 of the 210 control sera from healthy donors. This finding thus led to a kit sensitivity, specificity, and accuracy of 100, 99.5, and 99.6%, respectively. The test thus provided a positive predictive value (PPV) of 98.7% and a negative predictive value (NPV) of 100%. In addition, the ELISA gave a positive delta of 5.4 and a negative delta of 3.6, indicating an excellent differentiation between positives and negatives. The same recombinant proteins were also applied to a newly developed platform for the development of a 15-min rapid test. The resulting rapid test has an excellent agreement of 99.6%, with a kappa value of 1.00, with the ELISA. Again, this rapid test was able to detect 100% of the samples tested (n = 42) while maintaining a specificity of 99.0% (n = 210). The PPV and NPV for the rapid test thus reached 95.3 and 100%, respectively.",,"['Guan, Ming', 'Chen, Hsiao Ying', 'Yun Foo, Shen', 'Tan, Yee-Joo', 'Goh, Phuay-Yee', 'Wee, Shock Hwa']",,,,
,PMC,Effects of Infection with Transmissible Gastroenteritis Virus on Concomitant Immune Responses to Dietary and Injected Antigens,http://dx.doi.org/10.1128/CDLI.11.2.337-343.2004,PMC371216,,,"Normal piglets weaned onto soy- or egg-based diets generated antibody responses to fed protein. Concurrent infection with transmissible gastroenteritis virus (TGEV) did not affect the responses to dietary antigens at weaning, nor did it affect the subsequent development of tolerance. However, TGEV infection did enhance the primary immunoglobulin M (IgM) and IgG1, but not IgG2, antibody responses to injected soy in comparison to those of uninfected animals. Paradoxically, TGEV-infected animals showed an enhanced primary IgG1 antibody response to injected soy at 4 weeks of age, but they subsequently showed a reduced secondary response after an intraperitoneal challenge at 9 weeks of age in comparison to uninfected animals. The results suggest that an enteric virus, either used as a vaccine vector or present as a subclinical infection, may not have significant effects on the development of dietary allergies but may have effects both on the primary response and on the subsequent recall response to systemic antigens to which the animal is exposed concurrently with virus antigens.",,"['Bailey, Michael', 'Haverson, Karin', 'Miller, Bevis', 'Jones, Philip', 'Sola, Isabel', 'Enjuanes, Luis', 'Stokes, Christopher R.']",,,,
,PMC,Profiles of Antibody Responses against Severe Acute Respiratory Syndrome Coronavirus Recombinant Proteins and Their Potential Use as Diagnostic Markers,http://dx.doi.org/10.1128/CDLI.11.2.362-371.2004,PMC371215,,,"A new coronavirus (severe acute respiratory syndrome coronavirus [SARS-CoV]) has been identified to be the etiological agent of severe acute respiratory syndrome. Given the highly contagious and acute nature of the disease, there is an urgent need for the development of diagnostic assays that can detect SARS-CoV infection. For determination of which of the viral proteins encoded by the SARS-CoV genome may be exploited as diagnostic antigens for serological assays, the viral proteins were expressed individually in mammalian and/or bacterial cells and tested for reactivity with sera from SARS-CoV-infected patients by Western blot analysis. A total of 81 sera, including 67 from convalescent patients and seven pairs from two time points of infection, were analyzed, and all showed immunoreactivity towards the nucleocapsid protein (N). Sera from some of the patients also showed immunoreactivity to U274 (59 of 81 [73%]), a protein that is unique to SARS-CoV. In addition, all of the convalescent-phase sera showed immunoreactivity to the spike (S) protein when analyzed by an immunofluorescence method utilizing mammalian cells stably expressing S. However, samples from the acute phase (2 to 9 days after the onset of illness) did not react with S, suggesting that antibodies to N may appear earlier than antibodies to S. Alternatively, this could be due to the difference in the sensitivities of the two methods. The immunoreactivities to these recombinant viral proteins are highly specific, as sera from 100 healthy donors did not react with any of them. These results suggest that recombinant N, S, and U274 proteins may be used as antigens for the development of serological assays for SARS-CoV.",,"['Tan, Yee-Joo', 'Goh, Phuay-Yee', 'Fielding, Burtram C.', 'Shen, Shuo', 'Chou, Chih-Fong', 'Fu, Jian-Lin', 'Nam Leong, Hoe', 'Sin Leo, Yee', 'Eong Ooi, Eng', 'Ee Ling, Ai', 'Gee Lim, Seng', 'Hong, Wanjin']",,,,
,PMC,Development of a Western Blot Assay for Detection of Antibodies against Coronavirus Causing Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1128/CDLI.11.2.417-422.2004,PMC371214,,,"To identify a major antigenic determinant for use in the development of a rapid serological diagnostic test for severe acute respiratory syndrome (SARS) coronavirus infection and to study the immune response during SARS coronavirus infection in humans, we cloned the full length and six truncated fragments of the nucleocapsid gene, expressed them, and purified them as glutathione S-transferase-tagged recombinant proteins. The reactivities of the recombinant proteins to a panel of antibodies containing 33 SARS coronavirus-positive sera and 66 negative sera and to antibodies against other animal coronaviruses were screened. A truncated 195-amino-acid fragment from the C terminus of the nucleocapsid protein (N195) was identified that had a strong ability to detect antibodies against SARS coronavirus. No cross-reaction was found between the N195 protein and antibodies against chicken, pig, and canine coronaviruses. The N195 protein was used to develop a Western blot assay to detect antibodies against SARS coronavirus in 274 clinically blinded samples. The specificity and sensitivity of this test were 98.3 and 90.9%, respectively. The correlation between our Western blotting assay and an immunofluorescence assay (IFA) was also analyzed. The results of our Western blot assay and IFA for the detection of SARS coronavirus-positive sera were the same. Thus, the N195 protein was identified as a suitable protein to be used as an antigen in Western blot and other possible assays for the detection of SARS coronavirus infection.",,"['He, Qigai', 'Chong, Kooi Hoong', 'Hee Chng, Hiok', 'Leung, Bernard', 'Ee Ling, Ai', 'Wei, Ting', 'Chan, Shzu-Wei', 'Eong Ooi, Eng', 'Kwang, Jimmy']",,,,
,PMC,Prolonged disturbances of in vitro cytokine production in patients with severe acute respiratory syndrome (SARS) treated with ribavirin and steroids,http://dx.doi.org/10.1111/j.1365-2249.2003.02391.x,PMC1808981,,,"Severe acute respiratory syndrome (SARS) is a new disease which has spread rapidly and widely. We wished to know whether evaluation of in vitro cytokine production could contribute to improved understanding of disease pathogenesis and to better patient management. Numbers of unstimulated and mitogen-stimulated cytokine-secreting peripheral blood mononuclear cells were measured repeatedly during and after hospitalization in 13 patients with SARS using enzyme-linked immunospot technology. Numbers of interferon-gamma, interleukin (IL)-2, IL-4, IL-10 and IL-12 secreting cells induced by T cell activators were below normal in many or most patients before and during treatment with corticosteroids and ribavirin but returned essentially to normal after completion of treatment. Staphylococcus aureus Cowan 1 (SAC)-stimulated IL-10 secreting cells were increased in early SARS but fell during treatment. SAC-induced IL-12 secreting cells were deficient before, during and long after treatment. Numbers of cells induced to produce IL-6 and tumour necrosis factor-alpha by T cell or monocyte activators were higher than normal in many early SARS patients and were still increased in some during and after treatment. We conclude that prolonged dysregulated cytokine production occurs in SARS and that future studies should be directed at improving anti-inflammatory and antiviral therapies in order to limit cytokine impairment.",,"['JONES, B M', 'MA, E S K', 'PEIRIS, J S M', 'WONG, P C', 'HO, J C M', 'LAM, B', 'LAI, K N', 'TSANG, K W T']",,,,
,PMC,Severe acute respiratory syndrome (SARS): a review,http://dx.doi.org/10.7861/clinmedicine.4-2-152,PMC4954004,,,"Severe acute respiratory syndrome (SARS) is a newly emerged disease that rapidly spread around the world. The disease originated in southern China and a novel coronavirus (SARS CoV) has been implicated as the causative organism. The path this virus took to set up human infection remains a mystery, though preliminary data point to origins in an animal reservoir. Nosocomial transmission of SARS CoV has been a striking feature in this epidemic. The clinical illness is similar to many acute respiratory infections, although a large proportion of patients show a rapid deterioration with respiratory distress towards the end of the second week of illness. The management principles are broadly similar to treating any community acquired pneumonia but the infection control measures take a pivotal role. There is no proven antiviral agent against SARS CoV. The most remarkable feature about the SARS epidemic was the speed with which the global community acted in a coordinated way to control it.",,"['Vijayanand, Pandurangan', 'Wilkins, Ed', 'Woodhead, Mark']",,,,
,PMC,"The Faculty of Accident & Emergency Medicine Tenth Anniversary Meeting, 13–15 November 2003, Royal College of Surgeons of England, London, WC2A 3PE",,PMC1726249,,,,,,,,,
,PMC,"Tracking the Evolution of the SARS Coronavirus Using High-Throughput, High-Density Resequencing Arrays",http://dx.doi.org/10.1101/gr.2141004,PMC353227,,,"Mutations in the SARS-Coronavirus (SARS-CoV) can alter its clinical presentation, and the study of its mutation patterns in human populations can facilitate contact tracing. Here, we describe the development and validation of an oligonucleotide resequencing array for interrogating the entire 30-kb SARS-CoV genome in a rapid, cost-effective fashion. Using this platform, we sequenced SARS-CoV genomes from Vero cell culture isolates of 12 patients and directly from four patient tissues. The sequence obtained from the array is highly reproducible, accurate (>99.99% accuracy) and capable of identifying known and novel variants of SARS-CoV. Notably, we applied this technology to a field specimen of probable SARS and rapidly deduced its infectious source. We demonstrate that array-based resequencing-by-hybridization is a fast, reliable, and economical alternative to capillary sequencing for obtaining SARS-CoV genomic sequence on a population scale, making this an ideal platform for the global monitoring of SARS-CoV and other small-genome pathogens.",,"['Wong, Christopher W.', 'Albert, Thomas J.', 'Vega, Vinsensius B.', 'Norton, Jason E.', 'Cutler, David J.', 'Richmond, Todd A.', 'Stanton, Lawrence W.', 'Liu, Edison T.', 'Miller, Lance D.']",,,,
,PMC,"Preclinical Evaluation of Two Real-Time, Reverse Transcription-PCR Assays for Detection of the Severe Acute Respiratory Syndrome Coronavirus",http://dx.doi.org/10.1128/JCM.42.3.987-991.2004,PMC356893,,,"We verified the analytical performance characteristics of a previously described real-time reverse transcription-PCR (RT-PCR) assay targeting the open reading frame (ORF) 1b region of the severe acute respiratory syndrome coronavirus (SARS-CoV) with RNA transcripts. We then compared it to a novel nucleocapsid gene real-time RT-PCR assay with genomic RNA. The assays differed only in the primer and probe sequences and final concentrations. A commercially available armored RNA (Ambion, Austin, Tex.) was evaluated as positive control for the ORF 1b assay. The analytical sensitivity, reproducibility, amplification efficiency, and dynamic range of the assays were similar. Both were specific for SARS-CoV as determined by testing against human CoV 229E and OC43, specimens from patients without SARS, and by BLAST searches of GenBank for primer and probe sequence homology. The armored RNA was found to be a suitable positive control for the ORF 1b assay that could be reliably recovered and amplified from a variety of clinical specimens.",,"['Bressler, Adam M.', 'Nolte, Frederick S.']",,,,
,PMC,Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS),http://dx.doi.org/10.1136/jcp.2003.013276,PMC1770245,,,"Background: Severe acute respiratory syndrome (SARS) became a worldwide outbreak with a mortality of 9.2%. This new human emergent infectious disease is dominated by severe lower respiratory illness and is aetiologically linked to a new coronavirus (SARS-CoV). Methods: Pulmonary pathology and clinical correlates were investigated in seven patients who died of SARS in whom there was a strong epidemiological link. Investigations include a review of clinical features, morphological assessment, histochemical and immunohistochemical stainings, ultrastructural study, and virological investigations in postmortem tissue. Results: Positive viral culture for coronavirus was detected in most premortem nasopharyngeal aspirate specimens (five of six) and postmortem lung tissues (two of seven). Viral particles, consistent with coronavirus, could be detected in lung pneumocytes in most of the patients. These features suggested that pneumocytes are probably the primary target of infection. The pathological features were dominated by diffuse alveolar damage, with the presence of multinucleated pneumocytes. Fibrogranulation tissue proliferation in small airways and airspaces (bronchiolitis obliterans organising pneumonia-like lesions) in subpleural locations was also seen in some patients. Conclusions: Viable SARS-CoV could be isolated from postmortem tissues. Postmortem examination allows tissue to be sampled for virological investigations and ultrastructural examination, and when coupled with the appropriate lung morphological changes, is valuable to confirm the diagnosis of SARS-CoV, particularly in clinically unapparent or suspicious but unconfirmed cases.",,"['Tse, G M-K', 'To, K-F', 'Chan, P K-S', 'Lo, A W I', 'Ng, K-C', 'Wu, A', 'Lee, N', 'Wong, H-C', 'Mak, S-M', 'Chan, K-F', 'Hui, D S C', 'Sung, J J-Y', 'Ng, H-K']",,,,
,PMC,Sputum cytology of patients with severe acute respiratory syndrome (SARS),http://dx.doi.org/10.1136/jcp.2003.012948,PMC1770235,,,"Background: Severe acute respiratory syndrome (SARS) is a newly described form of atypical pneumonia linked to a novel coronavirus. Aims: To review the sputum cytology of 15 patients who fulfilled the World Health Organisation clinical criteria for SARS in an attempt to evaluate whether early diagnosis is feasible with routine sputum examination. Methods: All sputum samples from patients with SARS from the four major hospitals in Hong Kong were reviewed; abnormalities were sought in the cellular component, including abnormal numbers and morphology of the component cells compared with those from age matched controls taken over the same period one year ago. Results: Fifteen sputum samples from patients were compared with 25 control samples. In the patients with SARS, loose aggregates of macrophages were seen more frequently in the sputum. These macrophages frequently showed morphological changes, such as cytoplasmic foaminess, vacuole formation, and nuclear changes (including multinucleation and a ground glass appearance) when compared with the control samples. Conclusions: The cytological features of SARS are non-specific, but the observation of any of the described features should prompt further investigations, especially in patients with suspicious clinical features.",,"['Tse, G M K', 'Hui, P-K', 'Ma, T K F', 'Lo, A W I', 'To, K-F', 'Chan, W Y', 'Chow, L T C', 'Ng, H-K']",,,,
,PMC,"How did general practitioners protect themselves, their family, and staff during the SARS epidemic in Hong Kong?",http://dx.doi.org/10.1136/jech.2003.015594,PMC1732708,,,"Context: Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease and how the frontline community doctors respond to it is not known. Objectives: To explore the impact of SARS on general practitioners (GPs) in Hong Kong. Design: A cross sectional survey. Setting: Community based primary care clinics. Participants: 183 family medicine tutors affiliated with a local university. Postal survey sent to all tutors with a 74.8% response rate. Main outcome measures: Change of clinical behaviour and practices during the epidemic; anxiety level of primary care doctors. Results: All agreed SARS had changed their clinical practices. Significant anxiety was found in family doctors. Three quarters of respondents recalled requesting more investigations while a quarter believed they had over-prescribed antibiotics. GPs who were exposed to SARS or who had worked in high infection districts were less likely to quarantine themselves (10.8% versus 33.3%; p<0.01; 6.5% versus 27.5%; p<0.01 respectively). Exposure to SARS, the infection rates in their working district, and anxiety levels had significant impact on the level of protection or prescribing behaviour. Conclusion: The clinical practice of GPs changed significantly as a result of SARS. Yet, those did not quarantine themselves suggesting other factors may have some part to play. As failure to apply isolation precautions to suspected cases of SARS was one major reason for its spread, a contingency plan from the government to support family doctors is of utmost importance. Interface between private and public sectors are needed in Hong Kong to prepare for any future epidemics.",,"['Wong, W', 'Lee, A', 'Tsang, K', 'Wong, S']",,,,
,PMC,"Modelling potential responses to severe acute respiratory syndrome in Japan: the role of initial attack size, precaution, and quarantine",http://dx.doi.org/10.1136/jech.2003.014894,PMC1732706,,,"Background: There has been an outbreak of the severe acute respiratory syndrome (SARS) worldwide. With the use of detailed epidemiological data from other countries, this article describes the possible reason for the SARS epidemic not appearing in Japan, and simulates the impact of different control strategies that can break the transmission cycle of SARS associated coronavirus. Method: Mathematical modelling is used for predicting the epidemiological outcome and simultaneously for evaluating the effect of interventions on SARS. The study estimates the initial attack size that would result in failed invasion. Three different interventions have been incorporated into the public health response policies; precautionary public health measures, isolation of infected people, and quarantine of exposed humans. Results: The maximum number of humans newly infected could be roughly estimated on the basis of the initial attack size, using simple formulas. It is seen that the introduction of only a few cases into certain communities would not lead easily to an epidemic. The possible trajectories of SARS epidemic depend on the levels of public health interventions as quarantine and precautionary public health measures greatly affected the transmissibility of the disease. It is shown that there exist threshold levels of interventions at which the SARS epidemic settles down. Conclusion: Initial attack size is one of the determinants of whether SARS can successfully invade the community or not. Two of the most effective policy procedures to prevent new infections would be to apply stringent precautionary measures and to impose quicker and more effective quarantine of the exposed populace.",,"['Nishiura, H', 'Patanarapelert, K', 'Sriprom, M', 'Sarakorn, W', 'Sriyab, S', 'Ming, T']",,,,
,PMC,5-Minute Clinical Consults,http://dx.doi.org/10.1111/j.1525-1497.2004.Review.x,PMC1492161,,,,,"Watkins, Raquel S",,,,
,PMC,Live Poultry Markets Raised Flu and SARS Concern,,PMC2594892,,,,,"Dawson, George",,,,
,PMC,Identification and Characterization of Viral Structural Proteins of Infectious Salmon Anemia Virus,http://dx.doi.org/10.1128/JVI.78.6.3063-3071.2004,PMC353767,,,"Infectious salmon anemia virus (ISAV) is an unclassified Orthomyxovirus that has been shown to contain a segmented genome with eight single-stranded RNA species coding for 10 viral proteins. Four major structural proteins were characterized in the present study: two glycosylated proteins with estimated molecular masses of 42 and 50 kDa, one 66-kDa phosphoprotein, and one 22-kDa protein. Examination of lysed virions revealed the two glycoproteins and the 22-kDa protein in the soluble fraction, while the 66-kDa phosphoprotein and a minor part of the 22-kDa protein were found in the pelleted fraction. Immunofluorescence staining of infected cells demonstrated that the 22-kDa protein was a late protein accumulating in the nucleus. We conclude that the 66-kDa protein is the nucleoprotein, the 22-kDa protein is the matrix protein, and the 42- and 50-kDa proteins are the surface proteins. Radioimmunoprecipitation analysis of the 42-kDa glycoprotein, which was previously shown to represent the ISAV hemagglutinin, indicated that this protein exists at least as dimers. Further, by labeling of purified ISAV with [1,3-(3)H]diisopropyl fluorophosphate, it was also demonstrated that the viral esterase is located with the hemagglutinin. This finding was confirmed by demonstration of acetylesterase activity in affinity-purified hemagglutinin preparations. Finally, the active-site serine residue could be tentatively identified at position 32 within the amino acid sequence of the hemagglutinin of ISAV strain Glesvaer/2/90. It is proposed that the ISAV vp66 protein be termed nucleoprotein, the gp42 protein be termed HE protein, and the vp22 protein be termed matrix protein.",,"['Falk, Knut', 'Aspehaug, Vidar', 'Vlasak, Reinhard', 'Endresen, Curt']",,,,
,PMC,Infectious Salmon Anemia Virus Specifically Binds to and Hydrolyzes 4-O-Acetylated Sialic Acids,http://dx.doi.org/10.1128/JVI.78.6.3055-3062.2004,PMC353765,,,"Infectious salmon anemia virus (ISAV) is the causative agent of infections in farmed Atlantic salmon. ISAV presumably represents a new genus within the Orthomyxoviridae. ISAV has been shown earlier to exhibit a receptor-destroying activity, which was defined as an acetylesterase with unknown specificity. We have analyzed the substrate specificity of the ISAV esterase in detail. Purified ISAV hydrolyzed free 5-N-acetyl-4-O-acetyl neuraminic acid. In addition, the purified 9-O-acetylated sialic acid derivative was also hydrolyzed, but at lower rates. When we used a glycosidically bound substrate, ISAV was unable to hydrolyze 9-O-acetylated sialic acid, which represents the major substrate for the influenza C virus esterase. ISAV completely de-O-acetylated glycoprotein-bound 5-N-acetyl-4-O-acetyl neuraminic acid. Thus, the enzymatic activity of the hemagglutinin-esterase of ISAV is comparable to that of the sialate-4-O-esterases of murine coronaviruses and related group 2 coronaviruses. In addition, we found that ISAV specifically binds to glycoproteins containing 4-O-acetylated sialic acids. Both the ISAV esterase and recombinant rat coronavirus esterase specific for 4-O-acetylated sialic acids hydrolyzed ISAV receptors on horse and rabbit erythrocytes, indicating that this sialic acid represents a receptor determinant for ISAV.",,"['Hellebø, Audny', 'Vilas, Ulrike', 'Falk, Knut', 'Vlasak, Reinhard']",,,,
,PMC,Requirements for CEACAMs and Cholesterol during Murine Coronavirus Cell Entry,http://dx.doi.org/10.1128/JVI.78.6.2682-2692.2004,PMC353758,,,"Previous reports have documented that cholesterol supplementations increase cytopathic effects in tissue culture and also intensify in vivo pathogenicities during infection by the enveloped coronavirus murine hepatitis virus (MHV). To move toward a mechanistic understanding of these phenomena, we used growth media enriched with methyl-β-cyclodextrin or cholesterol to reduce or elevate cellular membrane sterols, respectively. Cholesterol depletions reduced plaque development 2- to 20-fold, depending on the infecting MHV strain, while supplementations increased susceptibility 2- to 10-fold. These various cholesterol levels had no effect on the binding of viral spike (S) proteins to cellular carcinoembryonic antigen-related cell adhesion molecule (CEACAM) receptors, rather they correlated directly with S-protein-mediated membrane fusion activities. We considered whether cholesterol was indirectly involved in membrane fusion by condensing CEACAMs into “lipid raft” membrane microdomains, thereby creating opportunities for simultaneous binding of multiple S proteins that subsequently cooperate in the receptor-triggered membrane fusion process. However, the vast majority of CEACAMs were solubilized by cold Triton X-100 (TX-100), indicating their absence from lipid rafts. Furthermore, engineered CEACAMs appended to glycosylphosphatidylinositol anchors partitioned with TX-100-resistant lipid rafts, but cells bearing these raft-associated CEACAMs were not hypersensitive to MHV infection. These findings argued against the importance of cholesterol-dependent CEACAM localizations into membrane microdomains for MHV entry, instead suggesting that cholesterol had a more direct role. Indeed, we found that cholesterol was required even for those rare S-mediated fusions taking place in the absence of CEACAMs. We conclude that cholesterol is an essential membrane fusion cofactor that can act with or without CEACAMs to promote MHV entry.",,"['Thorp, Edward B.', 'Gallagher, Thomas M.']",,,,
,PMC,Presence of an Encephalomyocarditis Virus Internal Ribosome Entry Site Sequence in Avian Infectious Bronchitis Virus Defective RNAs Abolishes Rescue by Helper Virus,http://dx.doi.org/10.1128/JVI.78.6.2711-2721.2004,PMC353753,,,"Avian infectious bronchitis virus (IBV) defective RNAs (D-RNAs) have been used for the expression of heterologous genes in a helper-virus-dependent expression system. The heterologous genes were expressed under the control of an IBV transcription-associated sequence (TAS) derived from gene 5 of IBV Beaudette. However, coronavirus D-RNA expression vectors display an inherent instability following serial passage with helper virus, resulting in the eventual loss of the heterologous genes. The use of the picornavirus encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES) sequence to initiate gene translation was investigated as an alternative method to the coronavirus-mediated TAS-controlled heterologous gene expression system. IBV D-RNAs containing the chloramphenicol acetyltransferase (CAT) reporter gene, under EMCV IRES control, were assessed for IRES-mediated CAT protein translation. CAT protein was detected from T7-derived IBV D-RNA transcripts in a cell-free protein synthesis system and in situ in avian chick kidney (CK) cells following T7-derived D-RNA synthesis from a recombinant fowlpox virus expressing the bacteriophage T7 DNA-dependent RNA polymerase. However, CAT protein was not detected in CK cells from IRES-containing IBV D-RNAs, in which the IRES-CAT construct was inserted at two different positions within the D-RNA, in the presence of helper IBV. Northern blot analysis demonstrated that the IRES-containing D-RNAs were not rescued on serial passage with helper virus, indicating that the EMCV IRES sequence had a detrimental effect on IBV D-RNA rescue.",,"['Dove, Brian', 'Cavanagh, David', 'Britton, Paul']",,,,
,PMC,Transfusion and risk of infection in Canada: UPDATE 2004,,PMC2720478,,,,,,,,,
,PMC,Overlapping agendas or serendipitous synergism,,PMC2720477,,,,,"Stanwick, Richard",,,,
,PMC,Secondary structure and function of the 5′-proximal region of the equine arteritis virus RNA genome,http://dx.doi.org/10.1261/rna.5174804,PMC1370938,,,"Nidoviruses produce an extensive 3′-coterminal nested set of subgenomic mRNAs, which are used to express their structural proteins. In addition, arterivirus and coronavirus mRNAs contain a common 5′ leader sequence, derived from the genomic 5′ end. The joining of this leader sequence to different segments (mRNA bodies) from the genomic 3′-proximal region presumably involves a unique mechanism of discontinuous minus-strand RNA synthesis. Key elements in this process are the so-called transcription-regulating sequences (TRSs), which determine a base-pairing interaction between sense and antisense viral RNA that is essential for leader-to-body joining. To identify RNA structures in the 5′-proximal region of the equine arteritis virus genome that may be involved in subgenomic mRNA synthesis, a detailed secondary RNA structure model was established using bioinformatics, phylogenetic analysis, and RNA structure probing. According to this structure model, the leader TRS is located in the loop of a prominent hairpin (leader TRS hairpin; LTH). The importance of the LTH was supported by the results of a mutagenesis study using an EAV molecular clone. Besides evidence for a direct role of the LTH in subgenomic RNA synthesis, indications for a role of the LTH region in genome replication and/or translation were obtained. Similar LTH structures could be predicted for the 5′-proximal region of all arterivirus genomes and, interestingly, also for most coronaviruses. Thus, we postulate that the LTH is a key structural element in the discontinuous subgenomic RNA synthesis and is likely critical for leader TRS function.",,"['VAN DEN BORN, ERWIN', 'GULTYAEV, ALEXANDER P.', 'SNIJDER, ERIC J.']",,,,
,PMC,Prediction of RNA-binding proteins from primary sequence by a support vector machine approach,http://dx.doi.org/10.1261/rna.5890304,PMC1370931,,,"Elucidation of the interaction of proteins with different molecules is of significance in the understanding of cellular processes. Computational methods have been developed for the prediction of protein–protein interactions. But insufficient attention has been paid to the prediction of protein–RNA interactions, which play central roles in regulating gene expression and certain RNA-mediated enzymatic processes. This work explored the use of a machine learning method, support vector machines (SVM), for the prediction of RNA-binding proteins directly from their primary sequence. Based on the knowledge of known RNA-binding and non-RNA-binding proteins, an SVM system was trained to recognize RNA-binding proteins. A total of 4011 RNA-binding and 9781 non-RNA-binding proteins was used to train and test the SVM classification system, and an independent set of 447 RNA-binding and 4881 non-RNA-binding proteins was used to evaluate the classification accuracy. Testing results using this independent evaluation set show a prediction accuracy of 94.1%, 79.3%, and 94.1% for rRNA-, mRNA-, and tRNA-binding proteins, and 98.7%, 96.5%, and 99.9% for non-rRNA-, non-mRNA-, and non-tRNA-binding proteins, respectively. The SVM classification system was further tested on a small class of snRNA-binding proteins with only 60 available sequences. The prediction accuracy is 40.0% and 99.9% for snRNA-binding and non-snRNA-binding proteins, indicating a need for a sufficient number of proteins to train SVM. The SVM classification systems trained in this work were added to our Web-based protein functional classification software SVMProt, at http://jing.cz3.nus.edu.sg/cgi-bin/svmprot.cgi. Our study suggests the potential of SVM as a useful tool for facilitating the prediction of protein–RNA interactions.",,"['HAN, LIAN YI', 'CAI, CONG ZHONG', 'LO, SIEW LIN', 'CHUNG, MAXEY C.M.', 'CHEN, YU ZONG']",,,,
,PMC,Management of exacerbations of COPD,,PMC1766023,,,,,,,,,
,PMC,Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings,http://dx.doi.org/10.1136/thorax.2003.012658,PMC1746980,,,"Background: The clinical response of patients with severe acute respiratory syndrome (SARS) to a combination of lopinavir/ritonavir and ribavirin was examined after establishing the in vitro antiviral susceptibility of the SARS associated coronavirus to a panel of antiviral agents. Methods: The in vitro susceptibility of the prototype of SARS associated coronavirus to a panel of nucleoside analogues and protease inhibitors currently licensed for clinical use was studied. Forty one patients with SARS followed for 3 weeks were treated with a combination of lopinavir/ritonavir and ribavirin. The clinical progress and virological outcomes were monitored and compared with 111 patients treated with ribavirin only who served as historical controls. Results: In vitro antiviral activity against SARS associated coronavirus was demonstrated for lopinavir and ribavirin at concentrations of 4 µg/ml and 50 µg/ml, respectively, only at 48 hours. The adverse clinical outcome (ARDS or death) was significantly lower in the treatment group than in the historical controls (2.4% v 28.8%, p<0.001) at day 21 after the onset of symptoms. The adverse outcome remained significantly lower in the treatment group than in the controls—both those diagnosed early (p<0.001) and those diagnosed later in the course of the epidemic (p = 0.002)—but there was no significant difference in adverse outcome rates between the two time periods (p = 0.548). No time related difference in outcome was observed in the control groups. A reduction in steroid usage and nosocomial infections was seen in patients initially treated with lopinavir/ritonavir, and these patients had a decreasing viral load and rising peripheral lymphocyte count. Multivariate analysis showed that age, hepatitis B carrier status, and lack of treatment with this antiviral combination were independent predictors of an adverse outcome. Lopinavir/ritonavir treatment was associated with a better outcome even when adjusted for baseline lactate dehydrogenase level. Conclusions: The apparent favourable clinical response with lopinavir/ritonavir and ribavirin supports further randomised placebo controlled trials in patients with SARS.",,"['Chu, C', 'Cheng, V', 'Hung, I', 'Wong, M', 'Chan, K', 'Chan, K', 'Kao, R', 'Poon, L', 'Wong, C', 'Guan, Y', 'Peiris, J', 'Yuen, K']",,,,
,PMC,Respiratory medical societies and the threat of bioterrorism,http://dx.doi.org/10.1136/thorax.2003.015321,PMC1746971,,,,,"[""O'Riordan, T"", 'Smaldone, G']",,,,
,PMC,In brief,,PMC351835,,,,,,,,,
,PMC,WHO hopes 3-by-5 plan will reverse Africa's HIV/AIDS epidemic.,,PMC2585877,,,,,"Fleck, Fiona",,,,
,PMC,Polio control after certification: major issues outstanding.,,PMC2585872,,,"Now that the global eradication of wild poliovirus is almost within sight, planning for the post-certification era is becoming a priority issue. It is agreed that a stockpile of appropriate polio vaccines will need to be established, and a surveillance and response capacity will need to be maintained, in order to protect the world against any possible future outbreaks attributable either to the persistence of wild poliovirus or vaccine-derived polioviruses (VDPVs) or to the unintentional or intentional release of poliovirus from a laboratory or vaccine store. Although it has been suggested that the stockpile should consist of monovalent oral poliovirus vaccine (mOPV), many questions remain concerning its nature, financing, management, and use--in particular, because of uncertainties over future national vaccination policies, and over the availability of different vaccines, after the certification of wild poliovirus eradication. There are further uncertainties concerning the possible role and efficacy of inactivated poliovirus vaccine (IPV) used either routinely or in outbreak control in low-hygiene settings, the potential for rapid geographical spread of polioviruses should an outbreak occur after certification, and the risks inherent in introducing additional oral polio vaccine (OPV) viruses into populations in which the vaccine coverage and prevalence of immunity have declined, and which may thus favour the spread of VDPVs. Given these important gaps in knowledge, no country should discontinue polio vaccination until a coordinated policy for the post-certification era has been developed and the recommended measures have been put in place.",,"['Fine, Paul E. M.', 'Oblapenko, George', 'Sutter, Roland W.']",,,,
,PMC,Europe to have its own centre for disease control,,PMC344300,,,,,"Watson, Rory",,,,
,PMC,SARS respiratory protection: update,,PMC332692,,,,,"Lange, John H.",,,,
,PMC,Characterization of severe acute respiratory syndrome coronavirus genomes in Taiwan: Molecular epidemiology and genome evolution,http://dx.doi.org/10.1073/pnas.0307904100,PMC356986,,,"Since early March 2003, the severe acute respiratory syndrome (SARS) coronavirus (CoV) infection has claimed 346 cases and 37 deaths in Taiwan. The epidemic occurred in two stages. The first stage caused limited familial or hospital infections and lasted from early March to mid-April. All cases had clear contact histories, primarily from Guangdong or Hong Kong. The second stage resulted in a large outbreak in a municipal hospital, and quickly spread to northern and southern Taiwan from late April to mid-June. During this stage, there were some sporadic cases with untraceable contact histories. To investigate the origin and transmission route of SARS-CoV in Taiwan's epidemic, we conducted a systematic viral lineage study by sequencing the entire viral genome from ten SARS patients. SARS-CoV viruses isolated from Taiwan were found closely related to those from Guangdong and Hong Kong. In addition, all cases from the second stage belonged to the same lineage after the municipal hospital outbreak, including the patients without an apparent contact history. Analyses of these full-length sequences showed a positive selection occurring during SARS-CoV virus evolution. The mismatch distribution indicated that SARS viral genomes did not reach equilibrium and suggested a recent introduction of the viruses into human populations. The estimated genome mutation rate was ≈0.1 per genome, demonstrating possibly one of the lowest rates among known RNA viruses.",,"['Yeh, Shiou-Hwei', 'Wang, Hurng-Yi', 'Tsai, Ching-Yi', 'Kao, Chuan-Liang', 'Yang, Jyh-Yuan', 'Liu, Hwan-Wun', 'Su, Ih-Jen', 'Tsai, Shih-Feng', 'Chen, Ding-Shinn', 'Chen, Pei-Jer', None]",,,,
,PMC,Flu: A Medical Mystery,,PMC338121,,,"BBC Radio 4, 2 February at 8 pm Rating: ★★★",,"Katikireddi, Vittal",,,,
,PMC,In brief,,PMC338088,,,,,,,,,
,PMC,"A 9,000-year record of Chagas' disease",http://dx.doi.org/10.1073/pnas.0307312101,PMC357047,,,"Tissue specimens from 283 principally spontaneously (naturally) desiccated human mummies from coastal and low valley sites in northern Chile and southern Peru were tested with a DNA probe directed at a kinetoplast DNA segment of Trypanosoma cruzi. The time interval spanned by the eleven major cultural groups represented in the sample ranged from ≈9,000 years B.P. (7050 B.C.) to approximately the time of the Spanish conquest, ≈450 B.P. (≈1500 A.D.). Forty-one percent of the tissue extracts, amplified by the PCR reacted positively (i.e., hybridized) with the probe. Prevalence patterns demonstrated no statistically significant differences among the individual cultural groups, nor among subgroups compared on the basis of age, sex, or weight of specimen tested. These results suggest that the sylvatic (animal-infected) cycle of Chagas' disease was probably well established at the time that the earliest humans (members of the Chinchorro culture) first peopled this segment of the Andean coast and inadvertently joined the many other mammal species acting as hosts for this parasite.",,"['Aufderheide, Arthur C.', 'Salo, Wilmar', 'Madden, Michael', 'Streitz, John', 'Buikstra, Jane', 'Guhl, Felipe', 'Arriaza, Bernardo', 'Renier, Colleen', 'Wittmers, Lorentz E.', 'Fornaciari, Gino', 'Allison, Marvin']",,,,
,PMC,Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association,http://dx.doi.org/10.1073/pnas.0307140101,PMC356985,,,"Effective prophylaxis and antiviral therapies are urgently needed in the event of reemergence of the highly contagious and often fatal severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) infection. We have identified eight recombinant human single-chain variable region fragments (scFvs) against the S1 domain of spike (S) protein of the SARS-CoV from two nonimmune human antibody libraries. One scFv 80R efficiently neutralized SARS-CoV and inhibited syncytia formation between cells expressing the S protein and those expressing the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2). Mapping of the 80R epitope showed it is located within the N-terminal 261–672 amino acids of S protein and is not glycosylation-dependent. 80R scFv competed with soluble ACE2 for association with the S1 domain and bound S1 with high affinity (equilibrium dissociation constant, K(d) = 32.3 nM). A human IgG1 form of 80R bound S1 with a 20-fold higher affinity of 1.59 nM comparable to that of ACE2 (K(d) = 1.70 nM), and neutralized virus 20-fold more efficiently than the 80R scFv. These data suggest that the 80R human monoclonal antibody may be a useful viral entry inhibitor for the emergency prophylaxis and treatment of SARS, and that the ACE2-binding site of S1 could be an attractive target for subunit vaccine and drug development.",,"['Sui, Jianhua', 'Li, Wenhui', 'Murakami, Akikazu', 'Tamin, Azaibi', 'Matthews, Leslie J.', 'Wong, Swee Kee', 'Moore, Michael J.', 'Tallarico, Aimee St. Clair', 'Olurinde, Mobolaji', 'Choe, Hyeryun', 'Anderson, Larry J.', 'Bellini, William J.', 'Farzan, Michael', 'Marasco, Wayne A.']",,,,
,PMC,Differential Distribution of the JC Virus Receptor-Type Sialic Acid in Normal Human Tissues,,PMC1602281,,,"JC virus (JCV), a member of the polyomavirus family, causes a demyelinating disease of the central nervous system (CNS) in humans known as progressive multifocal leukoencephalopathy. Although glial cells are the principal target of JCV productive infection in progressive multifocal leukoencephalopathy patients, little is known regarding the site of JCV persistence and the mechanisms by which the virus spreads to the CNS to cause disease. Previous work has demonstrated the presence of replicating JCV DNA in B lymphocytes from peripheral blood, tonsil, and spleen and it has been hypothesized that lymphocytes may be one site of JCV persistence. Detection of viral gene products in renal tubules and excretion of JC virions in the urine suggests JCV persistence in the kidney. A respiratory route of viral transmission has also been hypothesized implicating the lung as another possible site of persistent JCV infection. Earlier studies from our laboratory have shown that terminal α2,6-linked sialic acid is a critical component of the JCV receptor. In this report we examined the tissue distribution of this JCV receptor-type sialic acid in a panel of normal human tissues. Our results demonstrate that in normal brain JCV receptor-type sialic acids are expressed on oligodendrocytes and astrocytes, but not on cortical neurons. The receptor-type sialic acid is also more highly expressed on B lymphocytes than on T lymphocytes in normal human spleen and tonsil. In addition, both the kidney and lung express abundant levels of α2-6-linked sialic acids. Our data show a striking correlation between the expression of the JCV receptor-type sialic acid on cells and their susceptibility to infection by the virus. These findings also support the hypothesis of JCV persistence in lymphoid tissue and B-cell-facilitated viral dissemination to the CNS.",,"['Eash, Sylvia', 'Tavares, Rosemarie', 'Stopa, Edward G.', 'Robbins, Scott H.', 'Brossay, Laurent', 'Atwood, Walter J.']",,,,
,PMC,Bystander CD8 T-Cell-Mediated Demyelination is Interferon-γ-Dependent in a Coronavirus Model of Multiple Sclerosis,,PMC1602263,,,"Mice infected with the coronavirus mouse hepatitis virus, strain JHM (JHM) develop a disease that shares many histological characteristics with multiple sclerosis. We previously demonstrated that JHM-infected mice that only have CD8 T cells specific for an epitope not in the virus develop demyelination on specific activation of these cells. Herein we show that this process of bystander T-cell-mediated demyelination is interferon-γ (IFN-γ)-dependent. The absence of IFN-γ abrogated demyelination but did not change T-cell infiltration or expression levels of inflammatory cytokines or chemokines in the spinal cord. These results are consistent with models in which IFN-γ contributes to CD8 T-cell-mediated demyelination by activation of macrophages/microglia, the final effector cells in the disease process.",,"['Dandekar, Ajai A.', 'Anghelina, Daniela', 'Perlman, Stanley']",,,,
,PMC,Application of data mining techniques in pharmacovigilance,http://dx.doi.org/10.1046/j.1365-2125.2003.01968.x,PMC1884444,,,"AIMS: To discuss the potential use of data mining and knowledge discovery in databases for detection of adverse drug events (ADE) in pharmacovigilance. METHODS: A literature search was conducted to identify articles, which contained details of data mining, signal generation or knowledge discovery in relation to adverse drug reactions or pharmacovigilance in medical databases. RESULTS: ADEs are common and result in significant mortality, and despite existing systems drugs have been withdrawn due to ADEs many years after licensing. Knowledge discovery in databases (KDD) is a technique which may be used to detect potential ADEs more efficiently. KDD involves the selection of data variables and databases, data preprocessing, data mining and data interpretation and utilization. Data mining encompasses a number of statistical techniques including cluster analysis, link analysis, deviation detection and disproportionality assessment which can be utilized to determine the presence of and to assess the strength of ADE signals. Currently the only data mining methods to be used in pharmacovigilance are those of disproportionality, such as the Proportional Reporting Ratio and Information Component, which have been used to analyse the UK Yellow Card Scheme spontaneous reporting database and the WHO Uppsala Monitoring Centre database. The association of pericarditis with practolol but not with other β-blockers, the association of captopril and other angiotensin-converting enzymes with cough, and the association of terfenadine with heart rate and rhythm disorders could be identified by mining the WHO database. CONCLUSION: In view of the importance of ADEs and the development of massive data storage systems and powerful computer systems, the use of data mining techniques in knowledge discovery in medical databases is likely to be of increasing importance in the process of pharmacovigilance as they are likely to be able to detect signals earlier than using current methods.",,"['Wilson, Andrew M', 'Thabane, Lehana', 'Holbrook, Anne']",,,,
,PMC,"Monkeypox, Marshfield Clinic and the Internet: Leveraging Information Technology for Public Health",,PMC1069065,,,,,"Reed, Kurt D.",,,,
,PMC,Perforin and Gamma Interferon-Mediated Control of Coronavirus Central Nervous System Infection by CD8 T Cells in the Absence of CD4 T Cells,http://dx.doi.org/10.1128/JVI.78.4.1739-1750.2004,PMC369505,,,"Infection of the central nervous system (CNS) with the neurotropic JHM strain of mouse hepatitis virus produces acute and chronic demyelination. The contributions of perforin-mediated cytolysis and gamma interferon (IFN-γ) secretion by CD8(+) T cells to the control of infection and the induction of demyelination were examined by adoptive transfer into infected SCID recipients. Untreated SCID mice exhibited uncontrolled virus replication in all CNS cell types but had little or no demyelination. Memory CD8(+) T cells from syngeneic wild-type (wt), perforin-deficient, or IFN-γ-deficient (GKO) donors all trafficked into the infected CNS in the absence of CD4(+) T cells and localized to similar areas. Although CD8(+) T cells from all three donors suppressed virus replication in the CNS, GKO CD8(+) T cells expressed the least antiviral activity. A distinct viral antigen distribution in specific CNS cell types revealed different mechanisms of viral control. While wt CD8(+) T cells inhibited virus replication in all CNS cell types, cytolytic activity in the absence of IFN-γ suppressed the infection of astrocytes, but not oligodendroglia. In contrast, cells that secreted IFN-γ but lacked cytolytic activity inhibited replication in oligodendroglia, but not astrocytes. Demyelination was most severe following viral control by wt CD8(+) T cells but was independent of macrophage infiltration. These data demonstrate the effective control of virus replication by CD8(+) T cells in the absence of CD4(+) T cells and support the necessity for the expression of distinct effector mechanisms in the control of viral replication in distinct CNS glial cell types.",,"['Bergmann, Cornelia C.', 'Parra, Beatriz', 'Hinton, David R.', 'Ramakrishna, Chandran', 'Dowdell, Konechi C.', 'Stohlman, Stephen A.']",,,,
,PMC,The Human Immunodeficiency Virus Type 1 Ribosomal Frameshifting Site Is an Invariant Sequence Determinant and an Important Target for Antiviral Therapy,http://dx.doi.org/10.1128/JVI.78.4.2082-2087.2004,PMC369415,,,"Human immunodeficiency virus type 1 (HIV-1) utilizes a distinctive form of gene regulation as part of its life cycle, termed programmed −1 ribosomal frameshifting, to produce the required ratio of the Gag and Gag-Pol polyproteins. We carried out a sequence comparison of 1,000 HIV-1 sequences at the slippery site (UUUUUUA) and found that the site is invariant, which is somewhat surprising for a virus known for its variability. This prompted us to prepare a series of mutations to examine their effect upon frameshifting and viral infectivity. Among the series of mutations were changes of the HIV-1 slippery site to those effectively utilized by other viruses, because such mutations would be anticipated to have a relatively mild effect upon frameshifting. The results demonstrate that any change to the slippery site reduced frameshifting levels and also dramatically inhibited infectivity. Because ribosomal frameshifting is essential for HIV-1 replication and it is surprisingly resistant to mutation, modulation of HIV-1 frameshifting efficiency potentially represents an important target for the development of novel antiviral therapeutics.",,"['Biswas, Preetha', 'Jiang, Xi', 'Pacchia, Annmarie L.', 'Dougherty, Joseph P.', 'Peltz, Stuart W.']",,,,
,PMC,Severe Acute Respiratory Syndrome Coronavirus Sequence Characteristics and Evolutionary Rate Estimate from Maximum Likelihood Analysis,http://dx.doi.org/10.1128/JVI.78.3.1602-1603.2004,PMC321409,,,,,"['Salemi, Marco', 'Fitch, Walter M.', 'Ciccozzi, Massimo', 'Ruiz-Alvarez, Maria Jose', 'Rezza, Giovanni', 'Lewis, Martha J.']",,,,
,PMC,Effects of an Epitope-Specific CD8(+) T-Cell Response on Murine Coronavirus Central Nervous System Disease: Protection from Virus Replication and Antigen Spread and Selection of Epitope Escape Mutants,http://dx.doi.org/10.1128/JVI.78.3.1150-1159.2004,PMC321401,,,"Both CD4(+) and CD8(+) T cells are required for clearance of the murine coronavirus mouse hepatitis virus (MHV) during acute infection. We investigated the effects of an epitope-specific CD8(+) T-cell response on acute infection of MHV, strain A59, in the murine CNS. Mice with CD8(+) T cells specific for gp33-41 (an H-2D(b)-restricted CD8(+) T-cell epitope derived from lymphocytic choriomeningitis glycoprotein) were infected with a recombinant MHV-A59, also expressing gp33-41, as a fusion protein with enhanced green fluorescent protein (EGFP). By 5 days postinfection, these mice showed significantly (approximately 20-fold) lower titers of infectious virus in the brain compared to control mice. Furthermore mice with gp33-41-specific CD8(+) cells exhibited much reduced levels of viral antigen in the brain as measured by immunohistochemistry using an antibody directed against viral nucleocapsid. More than 90% of the viruses recovered from brain lysates of such protected mice, at 5 days postinfection, had lost the ability to express EGFP and had deletions in their genomes encompassing EGFP and gp33-41. In addition, genomes of viruses from about half the plaques that retained the EGFP gene had mutations within the gp33-41 epitope. On the other hand, gp33-41-specific cells failed to protect perforin-deficient mice from infection by the recombinant MHV expressing gp33, indicating that perforin-mediated mechanisms were needed. Virus recovered from perforin-deficient mice did not exhibit loss of EGFP expression and the gp33-41 epitope. These observations suggest that the cytotoxic T-cell response to gp33-41 exerts a strong immune pressure that quickly selects epitope escape mutants to gp33-41.",,"['Chua, Ming Ming', 'MacNamara, Katherine C.', 'San Mateo, Lani', 'Shen, Hao', 'Weiss, Susan R.']",,,,
,PMC,An Acidic Cluster of Human Cytomegalovirus UL99 Tegument Protein Is Required for Trafficking and Function,http://dx.doi.org/10.1128/JVI.78.3.1488-1502.2004,PMC321399,,,"The human cytomegalovirus (HCMV) virion is comprised of a linear double-stranded DNA genome, proteinaceous capsid and tegument, and a lipid envelope containing virus-encoded glycoproteins. Of these components, the tegument is the least well defined in terms of both protein content and function. Several of the major tegument proteins are phosphoproteins (pp), including pp150, pp71, pp65, and pp28. pp28, encoded by the UL99 open reading frame (ORF), traffics to vacuole-like cytoplasmic structures and was shown recently to be essential for envelopment. To elucidate the UL99 amino acid sequences necessary for its trafficking and function in the HCMV replication cycle, two types of viral mutants were analyzed. Using a series of recombinant viruses expressing various UL99-green fluorescent protein fusions, we demonstrate that myristoylation at glycine 2 and an acidic cluster (AC; amino acids 44 to 57) are required for the punctate perinuclear and cytoplasmic (vacuole-like) localization observed for wild-type pp28. A second approach involving the generation of several UL99 deletion mutants indicated that at least the C-terminal two-thirds of this ORF is nonessential for viral growth. Furthermore, the data suggest that an N-terminal region of UL99 containing the AC is required for viral growth. Regarding virion incorporation or UL99-encoded proteins, we provide evidence that suggests that a hypophosphorylated form of pp28 is incorporated, myristoylation is required, and sequences within the first 57 amino acids are sufficient.",,"['Jones, Thomas R.', 'Lee, Shi-Wu']",,,,
,PMC,Human Cytomegalovirus Elicits a Coordinated Cellular Antiviral Response via Envelope Glycoprotein B,http://dx.doi.org/10.1128/JVI.78.3.1202-1211.2004,PMC321386,,,"Previous studies have shown that human cytomegalovirus (CMV) is a potent elicitor of interferon-stimulated gene (ISG) expression. Induction of the interferon pathway does not require replication-competent virus, and envelope glycoprotein B (gB) from CMV is a viral structural component that can directly induce transcription of ISGs. Here we extend these earlier findings by defining the consequences of inducing the interferon pathway. We found that cells respond to CMV or soluble gB by establishing a functional antiviral state within cell types critical in CMV biology, such as fibroblasts and endothelial cells. We have also discovered new insights into the mechanism by which the pathway is initiated. Interferon regulatory factor 3 (IRF3), a key transcriptional regulator of cellular interferon responses, is activated by CMV virions and soluble gB. Thus, IRF3 becomes activated via “outside-in” signal transduction events. This is a novel mechanism of activation of this key transcription factor by viruses. In comparison to soluble gB (gB(1-750)), which comprises the entire ectodomain of gB, a truncation mutant encompassing only the amino-terminal region of gB (gB(1-460)) was markedly less effective at inducing antiviral responses. This indicates that the region of gB from residues 461 to 750 is important for initiation of the antiviral response. In addition, CMV and gB establish an antiviral state in alpha/beta interferon null cells, illustrating that primary induction of ISGs by CMV and gB is sufficient to establish the antiviral response and that interferon secretion is not necessary for the antiviral effect. Taken together, our findings reveal that CMV initiates a coordinated antiviral response through contact between gB and an as-yet-unidentified cell surface receptor(s).",,"['Boehme, Karl W.', 'Singh, Jasbir', 'Perry, Stuart T.', 'Compton, Teresa']",,,,
,PMC,Neonatal congenital microvillus atrophy,http://dx.doi.org/10.1136/pmj.2003.007930,PMC1742937,,,"Congenital microvillous atrophy (CMVA) is the leading cause of neonatal secretory diarrhoea with onset either in the first 72 hours of life (early onset) or at 6–8 weeks after birth (late onset). To date over 30 cases have been reported worldwide. The prognosis for this life threatening condition continues to be poor. Therapeutic agents like somatostatin and epidermal growth factor are either ineffective or of marginal benefit. Overall five year survival after small bowel transplantation is currently ∼50%. The following brief review is aimed towards helping neonatologists/perinatologists in the early diagnosis, and management of CMVA and in counselling the parents appropriately.",,"['Pecache, N', 'Patole, S', 'Hagan, R', 'Hill, D', 'Charles, A', 'Papadimitriou, J']",,,,
,PMC,State-of-the-art psychiatric diagnosis,,PMC1414657,,,,,"Regier, Darrel A",,,,
,PMC,Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome,http://dx.doi.org/10.1073/pnas.0308352100,PMC337057,,,"Highly pathogenic avian influenza A viruses of subtypes H5 and H7 are the causative agents of fowl plague in poultry. Influenza A viruses of subtype H5N1 also caused severe respiratory disease in humans in Hong Kong in 1997 and 2003, including at least seven fatal cases, posing a serious human pandemic threat. Between the end of February and the end of May 2003, a fowl plague outbreak occurred in The Netherlands. A highly pathogenic avian influenza A virus of subtype H7N7, closely related to low pathogenic virus isolates obtained from wild ducks, was isolated from chickens. The same virus was detected subsequently in 86 humans who handled affected poultry and in three of their family members. Of these 89 patients, 78 presented with conjunctivitis, 5 presented with conjunctivitis and influenza-like illness, 2 presented with influenza-like illness, and 4 did not fit the case definitions. Influenza-like illnesses were generally mild, but a fatal case of pneumonia in combination with acute respiratory distress syndrome occurred also. Most virus isolates obtained from humans, including probable secondary cases, had not accumulated significant mutations. However, the virus isolated from the fatal case displayed 14 amino acid substitutions, some of which may be associated with enhanced disease in this case. Because H7N7 viruses have caused disease in mammals, including horses, seals, and humans, on several occasions in the past, they may be unusual in their zoonotic potential and, thus, form a pandemic threat to humans.",,"['Fouchier, Ron A. M.', 'Schneeberger, Peter M.', 'Rozendaal, Frans W.', 'Broekman, Jan M.', 'Kemink, Stiena A. G.', 'Munster, Vincent', 'Kuiken, Thijs', 'Rimmelzwaan, Guus F.', 'Schutten, Martin', 'van Doornum, Gerard J. J.', 'Koch, Guus', 'Bosman, Arnold', 'Koopmans, Marion', 'Osterhaus, Albert D. M. E.']",,,,
,PMC,New infectious diseases will continue to emerge,,PMC1140655,,,,,"Singh, Debashis",,,,
,PMC,"Outbreak of severe acute respiratory syndrome in a tertiary hospital in Singapore, linked to an index patient with atypical presentation: epidemiological study",http://dx.doi.org/10.1136/bmj.37939.465729.44,PMC318482,,,"Objective To describe an outbreak of severe acute respiratory syndrome (SARS) in a tertiary hospital in Singapore, linked to an index patient with atypical presentation, and the lessons learnt from it. Design Descriptive study. Setting A tertiary hospital in Singapore. Participants Patients, healthcare workers, and visitors who contracted SARS in Singapore General Hospital. Main outcome measures Probable SARS as defined by the World Health Organization. Results The index patient presented with gastrointestinal bleeding, initially without changes to his chest radiograph. Altogether 24 healthcare workers, 15 patients, and 12 family members and visitors were infected. The incubation period ranged from three to eight days. Only 13 patients were isolated on their dates of onset. Conclusions Atypical presentation of SARS infection must be taken into consideration when managing patients with a history of contact with SARS patients. The main gap in the containment strategy in this outbreak was the failure to identify the index patient as someone who had been discharged from a ward in another hospital that managed probable SARS cases. Strict infection control measures, a good surveillance system, early introduction of isolation procedures, and vigilant healthcare professionals are essential for controlling outbreaks.",,"['Chow, Khuan Yew', 'Lee, Chien Earn', 'Ling, Moi Lin', 'Heng, Derrick Mok Kwee', 'Yap, Soon Ghee']",,,,
,PMC,In brief,,PMC318477,,,,,,,,,
,PMC,Atypical presentation of SARS may generate an outbreak,,PMC318467,,,,,,,,,
,PMC,Intense selection in an age-structured population.,,PMC1691582,,,"In a population with overlapping generations, intense selection can perturb the age distribution and thus affect the rate of increase of an advantageous allele. We found that the age-specific nature of intense selection, such as that generated by many diseases, can affect the outcome of selection on loci, such as those conferring disease resistance. We also found that the temporal dynamics of selection alter the speed of evolution, particularly when selection is intense, and even more so when it is age-specific. We relate our model and results to selection for disease resistance, although the results have broader implications for inferences about past selection pressures in general.",,"['Galvani, Alison P.', 'Slatkin, Montgomery']",,,,
,PMC,Expert Committee finds little fault in Hong Kong's response to SARS.,,PMC2572353,,,,,"Marshall, Sarah Jane",,,,
,PMC,A Canadian Agency for Public Health: Could it work?,,PMC315528,,,,,"Wilson, Kumanan",,,,
,PMC,Canadian researchers testing SARS vaccine in China,,PMC315515,,,,,"Kondro, Wayne",,,,
,PMC,WHO queries culling of civet cats,,PMC1150312,,,,,"Parry, Jane",,,,
,PMC,In brief,,PMC314498,,,,,,,,,
,PMC,WHO confirms SARS in Chinese journalist,,PMC314040,,,,,"Parry, Jane",,,,
,PMC,Why SARS will not return: a polemic,,PMC305318,,,,,"Low, Donald E.",,,,
,PMC,Laboratory tests for SARS: Powerful or peripheral?,,PMC305315,,,,,"['Fouchier, Ron A.M.', 'Osterhaus, Ab D.M.E.']",,,,
,PMC,Interpretation of diagnostic laboratory tests for severe acute respiratory syndrome: the Toronto experience,,PMC305313,,,"BACKGROUND: An outbreak of severe acute respiratory syndrome (SARS) began in Canada in February 2003. The initial diagnosis of SARS was based on clinical and epidemiological criteria. During the outbreak, molecular and serologic tests for the SARS-associated coronavirus (SARS-CoV) became available. However, without a “gold standard,” it was impossible to determine the usefulness of these tests. We describe how these tests were used during the first phase of the SARS outbreak in Toronto and offer some recommendations that may be useful if SARS returns. METHODS: We examined the results of all diagnostic laboratory tests used in 117 patients admitted to hospitals in Toronto who met the Health Canada criteria for suspect or probable SARS. Focusing on tests for SARS-CoV, we attempted to determine the optimal specimen types and timing of specimen collection. RESULTS: Diagnostic test results for SARS-CoV were available for 110 of the 117 patients. SARS-CoV was detected by means of reverse-transcriptase polymerase chain reaction (RT-PCR) in at least one specimen in 59 (54.1%) of 109 patients. Serologic test results of convalescent samples were positive in 50 (96.2%) of 52 patients for whom paired serum samples were collected during the acute and convalescent phases of the illness. Of the 110 patients, 78 (70.9%) had specimens that tested positive by means of RT-PCR, serologic testing or both methods. The proportion of RT-PCR test results that were positive was similar between patients who met the criteria for suspect SARS (50.8%, 95% confidence interval [CI] 38.4%–63.2%) and those who met the criteria for probable SARS (58.0%, 95% CI 44.2%–70.7%). SARS-CoV was detected in nasopharyngeal swabs in 33 (32.4%) of 102 patients, in stool specimens in 19 (63.3%) of 30 patients, and in specimens from the lower respiratory tract in 10 (58.8%) of 17 patients. INTERPRETATION: These findings suggest that the rapid diagnostic tests in use at the time of the initial outbreak lack sufficient sensitivity to be used clinically to rule out SARS. As tests for SARS-CoV continue to be optimized, evaluation of the clinical presentation and elucidation of a contact history must remain the cornerstone of SARS diagnosis. In patients with SARS, specimens taken from the lower respiratory tract and stool samples test positive by means of RT-PCR more often than do samples taken from other areas.",,"['Tang, Patrick', 'Louie, Marie', 'Richardson, Susan E.', 'Smieja, Marek', 'Simor, Andrew E.', 'Jamieson, Frances', 'Fearon, Margaret', 'Poutanen, Susan M.', 'Mazzulli, Tony', 'Tellier, Raymond', 'Mahony, James', 'Loeb, Mark', 'Petrich, Astrid', 'Chernesky, Max', 'McGeer, Allison', 'Low, Donald E.', 'Phillips, Elizabeth', 'Jones, Steven', 'Bastien, Nathalie', 'Li, Yan', 'Dick, Daryl', 'Grolla, Allen', 'Fernando, Lisa', 'Booth, Timothy F.', 'Henry, Bonnie', 'Rachlis, Anita R.', 'Matukas, Larissa M.', 'Rose, David B.', 'Lovinsky, Reena', 'Walmsley, Sharon', 'Gold, Wayne L.', 'Krajden, Sigmund', None]",,,,
,PMC,New guidelines for severe respiratory infections,,PMC305300,,,,,"Gandey, Allison",,,,
,PMC,Prehospital intubation and SARS,,PMC305291,,,,,"Hutcheon, David J.",,,,
,PMC,Prehospital intubation and SARS,,PMC305290,,,,,"Urszenyi, Stephen L.",,,,
,PMC,Prehospital intubation and SARS,,PMC305289,,,,,"Ovens, Howard J.",,,,
,PMC,Prehospital intubation and SARS,,PMC305288,,,,,"Schabas, Richard E.",,,,
,PMC,Highlights of this issue,,PMC305276,,,,,,,,,
,PMC,WHO report says AIDS offers healthcare opportunity,,PMC313893,,,,,"Fleck, Fiona",,,,
,PMC,Blood transfusion,,PMC1755885,,,,,"['Bolton-Maggs, P', 'Murphy, M']",,,,
,PMC,"48th Annual Meeting February 14-18, 2004 Baltimore, Maryland: February 15, 2004 Sunday Posters, Part 2",,PMC1913839,,,,,,,,,
,PMC,Will the three steps for containment of poliovirus be enough to convince policy-makers?,,PMC2585889,,,,,"Schoub, BD.",,,,
,PMC,Containment of wild poliovirus in the laboratory is a realistic goal.,,PMC2585886,,,,,"Deshpande, JM.",,,,
,PMC,Can effective containment of wild polioviruses in laboratories and inactivated poliovirus vaccine production sites ever be achieved?,,PMC2585874,,,,,"Van Loon, AM.",,,,
,PMC,Poliovirus vaccine strains will continue to circulate long after wild strains have been eradicated.,,PMC2585871,,,,,"Schatzmayr, HG.",,,,
,PMC,SARS: A Local Public Health Perspective,http://dx.doi.org/10.1007/BF03403628,PMC6976208,,,,,"['Basrur, Sheela V.', 'Yaffe, Barbara', 'Henry, Bonnie']",,,,
,PMC,SARS: Lessons Learned from a Provincial Perspective,http://dx.doi.org/10.1007/BF03403629,PMC6976128,,,,,"D’Cunha, Colin",,,,
,PMC,Effect on hematopoietic tissue of experimental infection of calves with noncytopathic type 2 bovine viral diarrhea virus,,PMC1142128,,,"To investigate the hematologic abnormalities observed with noncytopathic type 2 bovine viral diarrhea virus (ncpBVDV-2), calves 6 to 8 mo old were inoculated with an isolate of either high virulence (HV24515) or low virulence (LV11Q); control animals received the same volume of uninfected cell-culture supernatant. Peripheral blood neutrophil, lymphocyte, and platelet counts decreased in all the virus-inoculated calves but were significantly lower and remained decreased longer in the calves given HV24515. For each isolate, a decrease in the number of mature myeloid cells in the bone marrow coincided with the development of neutropenia, but the depletion persisted significantly longer (4 to 6 d) in the calves given HV24515. In the bone marrow of calves given LV11Q, the number of proliferating myeloid cells increased in proportion to the decrease in the number of mature myeloid cells. In the calves inoculated with HV24515, BVDV antigen was observed in bone marrow cells when the peripheral blood counts were lowest. Megakaryocytes were the predominant cell type exhibiting positive BVDV staining; myeloid cells rarely stained positively. Viral antigen was not observed in the bone marrow of calves given LV11Q. These experiments demonstrated that ncpBVDV-2 isolates of both high and low virulence caused decreased leukocyte and platelet counts, but only the high-virulence HV24515 isolate caused a delay in the production of myeloid proliferating cells. The delay may contribute to the ability of certain ncpBVDV-2 isolates to induce severe disease.",,"['Wood, R. Darren', 'Goens, S. Denise', 'Carman, P. Suzanne', 'Deregt, Dirk', 'Jefferson, Barbara', 'Jacobs, Robert M.']",,,,
,PMC,Proceedings of the 10th Asian Pacific Congress of Clinical Biochemistry in conjunction with the Australasian Association of Clinical Biochemists' 42nd Annual Scientific Conference,,PMC1934963,,,,,,,,,
,PMC,Profile of Antibodies to the Nucleocapsid Protein of the Severe Acute Respiratory Syndrome (SARS)-Associated Coronavirus in Probable SARS Patients,http://dx.doi.org/10.1128/CDLI.11.1.227-228.2004,PMC321358,,,"Profiles of antibodies to the nucleocapsid protein of the severe acute respiratory syndrome (SARS)-associated coronavirus in 445 probable SARS patients and 3,749 healthy people or non-SARS patients were analyzed by antigen-capturing enzyme-linked immunosorbent assay. Antinucleocapsid antibodies were elucidated in 17.5% of the probable SARS patients 1 to 7 days after the onset of symptoms and in 80% of the patients 8 to 14 days after the onset. About 90% of the probable SARS patients were positive 15 or more days after illness. Antibody titers increased up to 70 days, and high antibody titers were maintained at least for another 3 months. Of the healthy people and non-SARS patients, only seven (0.187%) were weakly positive.",,"['Liu, Xuan', 'Shi, Yulin', 'Li, Ping', 'Li, Linhai', 'Yi, Yanping', 'Ma, Qingjun', 'Cao, Cheng']",,,,
,PMC,Fecal Immunoglobulin A Antibodies in Dogs Infected or Vaccinated with Canine Coronavirus,http://dx.doi.org/10.1128/CDLI.11.1.102-105.2004,PMC321341,,,"Fecal secretory immunoglobulin A (IgA) antibodies in dogs infected or vaccinated with canine coronavirus (CCV) were evaluated by an enzyme-linked immunosorbent assay. The study was carried out with 32 fecal samples collected just before inoculation and at 28 days postinoculation. Five groups were studied: naturally infected dogs, experimentally infected dogs, dogs inoculated with a modified live (ML) CCV vaccine by the intramuscular route, dogs inoculated with an ML CCV vaccine by the oronasal route, and dogs given an inactivated CCV vaccine. Both the naturally and the experimentally infected dogs developed high levels of fecal IgAs. Interestingly, dogs inoculated with the ML CCV vaccine by the oronasal route developed levels of fecal IgA that were higher than those observed in the dogs inoculated with the same CCV vaccine by the intramuscular route or those observed in dogs inoculated with the inactivated vaccine. A relationship between the level of fecal IgAs to CCV and the degree of protection against CCV infection was observed.",,"['Decaro, Nicola', 'Pratelli, Annamaria', 'Tinelli, Antonella', 'Martella, Vito', 'Camero, Michele', 'Buonavoglia, Domenico', 'Tempesta, Maria', 'Caroli, Anna Maria', 'Buonavoglia, Canio']",,,,
,PMC,Theiler's Virus Infection: a Model for Multiple Sclerosis,http://dx.doi.org/10.1128/CMR.17.1.174-207.2004,PMC321460,,,"Both genetic background and environmental factors, very probably viruses, appear to play a role in the etiology of multiple sclerosis (MS). Lessons from viral experimental models suggest that many different viruses may trigger inflammatory demyelinating diseases resembling MS. Theiler's virus, a picornavirus, induces in susceptible strains of mice early acute disease resembling encephalomyelitis followed by late chronic demyelinating disease, which is one of the best, if not the best, animal model for MS. During early acute disease the virus replicates in gray matter of the central nervous system but is eliminated to very low titers 2 weeks postinfection. Late chronic demyelinating disease becomes clinically apparent approximately 2 weeks later and is characterized by extensive demyelinating lesions and mononuclear cell infiltrates, progressive spinal cord atrophy, and axonal loss. Myelin damage is immunologically mediated, but it is not clear whether it is due to molecular mimicry or epitope spreading. Cytokines, nitric oxide/reactive nitrogen species, and costimulatory molecules are involved in the pathogenesis of both diseases. Close similarities between Theiler's virus-induced demyelinating disease in mice and MS in humans, include the following: major histocompatibility complex-dependent susceptibility; substantial similarities in neuropathology, including axonal damage and remyelination; and paucity of T-cell apoptosis in demyelinating disease. Both diseases are immunologically mediated. These common features emphasize the close similarities of Theiler's virus-induced demyelinating disease in mice and MS in humans.",,"['Oleszak, Emilia L.', 'Chang, J. Robert', 'Friedman, Herman', 'Katsetos, Christos D.', 'Platsoucas, Chris D.']",,,,
,PMC,"Effects and cost of glycyrrhizin in the treatment of upper respiratory tract infections in members of the Japanese maritime self-defense force: Preliminary report of a prospective, randomized, double-blind, controlled, parallel-group, alternate-day treatment assignment clinical trial",http://dx.doi.org/10.1016/S0011-393X(04)90002-1,PMC4052969,,,"Background: Upper respiratory tract infections (URTIs) account for at least half of all acute illnesses. Specific antiviral therapy has not been developed against most respiratory viruses thought to cause URTIs. The pharmacologic action of glycyrrhizin has been shown to produce anti-inflammatory activity, modulation of the immune system, inhibition of virus growth, and inactivation of viruses. Objective: The aim of this study was to assess the tolerability, efficacy, and cost of glycyrrhizin in improving the severity and duration of signs and symptoms of URTIs. The primary end point was tolerability, and the secondary and points included improvement in signs and symptoms of URTI and cost. Methods: Members of the Japanese Maritime Self-Defense Force (SDF) treated for URTIs from January 2002 to May 2002 in the SDF Etajima Hospital (Hiroshima, Japan) were eligible for this prospective, randomized, double-blind, controlled, parallel-group, alternate-day treatment assignment study. All patients in this study fulfilled the following enrollment criteria: admitted to the hospital on the first arrival day as an outpatient; fever (body temperature <38.0°C) with signs and symptoms of URTI (headache, sore throat, rhinorrhea, pharyngitis); and had not received antibiotics or oseltamivir phosphate for 4 weeks before the study. Patients who were admitted on an even day received an IV drip infusion of 40 mL of glycyrrhizin (0.2%) and 500 mL of lactated Ringer's solution daily during hospitalization (glycyrrhizin group). Patients who were admitted on an odd day received an IV drip infusion of 500 mL/d of lactated Ringer's solution only (control group). Adverse effects were assessed by the physicians during hospitalization, using patient interview and laboratory analysis. Results: Forty-one consecutive patients entered the study; 15 patients (15 men, 0 women; mean [SD] age, 25.2 [1.5] years) were assigned to the glycyrrhizin group and 269 patients (24 men, 2 women; mean [SD] age, 22.6 [0.9] years) were assigned to the control group. The 2 groups were similar in terms of baseline characteristics. The mean duration of hospitalization was shorter (P = 0.01), the mean maximum body temperature 24 to 48 hours after admission was less (P = 0.05), and the cost of therapy (P = 0.03) was less in the glycyrrhizin group than the control group. No AEs were reported. Conclusions: In this study of hospitalized patients with URTIs, glycyrrhizin therapy was associated with a shorter hospitalization, lower-grade fever, and lower cost of therapy compared with controls, showing that it may be beneficial to patients with URTIs without acute bacterial infections.",,"['Yanagawa, Youichi', 'Ogura, Masatsune', 'Fujimoto, Eita', 'Shono, Satoshi', 'Okuda, Eriya']",,,,
,PMC,Managing change in the emergency department: a personal view,http://dx.doi.org/10.1136/emj.2003.007559,PMC1756356,,,,,"Seow, E",,,,
,PMC,DIFFERENTIATED CULTURES OF PRIMARY HAMSTER TRACHEAL AIRWAY EPITHELIAL CELLS,http://dx.doi.org/10.1290/0408056.1,PMC1592688,,,"Primary airway epithelial cell cultures can provide a faithful representation of the in vivo airway while allowing for a controlled nutrient source and isolation from other tissues or immune cells. The methods used have significant differences based on tissue source, cell isolation, culture conditions, and assessment of culture purity. We modified and optimized a method for generating tracheal epithelial cultures from Syrian golden hamsters and characterized the cultures for cell composition and function. Soon after initial plating, the epithelial cells reached a high transepithelial resistance and formed tight junctions. The cells differentiated into a heterogeneous, multicellular culture containing ciliated, secretory, and basal cells after culture at an air–liquid interface (ALI). The secretory cell populations initially consisted of MUC5AC-positive goblet cells and MUC5AC/CCSP double-positive cells, but the makeup changed to predominantly Clara cell secretory protein (CCSP)–positive Clara cells after 14 d. The ciliated cell populations differentiated rapidly after ALI, as judged by the appearance of β tubulin IV–positive cells. The cultures produced mucus, CCSP, and trypsin-like proteases and were capable of wound repair as judged by increased expression of matrilysin. Our method provides an efficient, high-yield protocol for producing differentiated hamster tracheal epithelial cells that can be used for a variety of in vitro studies including tracheal cell differentiation, airway disease mechanisms, and pathogen–host interactions.",,"['ROWE, REGINA K.', 'BRODY, STEVEN L.', 'PEKOSZ, ANDREW']",,,,
,PMC,Stat-3 is required for pulmonary homeostasis during hyperoxia,http://dx.doi.org/10.1172/JCI200419491,PMC300770,,,"Acute lung injury syndromes remain common causes of morbidity and mortality in adults and children. Cellular and physiologic mechanisms maintaining pulmonary homeostasis during lung injury remain poorly understood. In the present study, the Stat-3 gene was selectively deleted in respiratory epithelial cells by conditional expression of Cre-recombinase under control of the surfactant protein C gene promoter. Cell-selective deletion of Stat-3 in respiratory epithelial cells did not alter prenatal lung morphogenesis or postnatal lung function. However, exposure of adult Stat-3–deleted mice to 95% oxygen caused a more rapidly progressive lung injury associated with alveolar capillary leak and acute respiratory distress. Epithelial cell injury and inflammatory responses were increased in the Stat-3–deleted mice. Surfactant proteins and lipids were decreased or absent in alveolar lavage material. Intratracheal treatment with exogenous surfactant protein B improved survival and lung histology in Stat-3–deleted mice during hyperoxia. Expression of Stat-3 in respiratory epithelial cells is not required for lung formation, but plays a critical role in maintenance of surfactant homeostasis and lung function during oxygen injury.",,"['Hokuto, Isamu', 'Ikegami, Machiko', 'Yoshida, Mitsuhiro', 'Takeda, Kiyoshi', 'Akira, Shizuo', 'Perl, Anne-Karina T.', 'Hull, William M.', 'Wert, Susan E.', 'Whitsett, Jeffrey A.']",,,,
,PMC,Human Metapneumovirus Infection in Japanese Children,http://dx.doi.org/10.1128/JCM.42.1.126-132.2004,PMC321731,,,"Human metapneumovirus (hMPV) has been recently discovered as an etiological agent of acute respiratory infections. Our purpose was to asses the virological and clinical features of children with respiratory infections caused by hMPV. We examined 658 nasopharyngeal swab samples obtained from 637 children with respiratory infections for hMPV by using reverse transcription-PCR (RT-PCR). A total of 268 samples from 637 children were inoculated onto tertiary monkey kidney cells. A total of 36 serum samples (26 in the acute phase and 10 in the convalescent phase) from the 26 hMPV-positive children were tested for immunoglobulin G (IgG) and IgM antibodies to hMPV by using an indirect immunofluorescence assay. We detected hMPV in 57 (8.9%) of the 637 samples by using RT-PCR and isolated 7 (2.6%) hMPV strains of the 268 samples in cell cultures. A total of 12 (46.2%) of 26 hMPV-positive children were suspected to have primary infection with hMPV as determined by an indirect immunofluorescence assay. The infected children were diagnosed as having wheezy bronchitis (36.8%), upper respiratory tract infection (26.3%), bronchitis (22.8%), and pneumonia (14.0%). We showed that two hMPV groups were circulating in different regions during the same period and that reinfection with hMPV frequently occurs in childhood. The RT-PCR test is the most sensitive test for detection of hMPV, and a serological test may be useful to differentiate between primary infection and reinfection with hMPV.",,"['Ebihara, Takashi', 'Endo, Rika', 'Kikuta, Hideaki', 'Ishiguro, Nobuhisa', 'Ishiko, Hiroaki', 'Hara, Michimaru', 'Takahashi, Yutaka', 'Kobayashi, Kunihiko']",,,,
,PMC,Detection of Severe Acute Respiratory Syndrome Coronavirus in Blood of Infected Patients,http://dx.doi.org/10.1128/JCM.42.1.347-350.2004,PMC321706,,,"Severe acute respiratory syndrome (SARS) has caused major outbreaks worldwide, resulting in an urgent need to obtain sensitive and accurate diagnosis of this disease. PCR-based detection methods were developed for use on a variety of samples, including blood. Eighteen subjects were investigated, and results indicated that blood samples contain sufficient virus for detection by using quantitative real-time PCR.",,"['Ng, Lisa F. P.', 'Wong, Michelle', 'Koh, Susie', 'Ooi, Eng-Eong', 'Tang, King-Fai', 'Leong, Hoe-Nam', 'Ling, Ai-Ee', 'Agathe, Lora V.', 'Tan, Jenny', 'Liu, Edison T.', 'Ren, Ee-Chee', 'Ng, Lee-Ching', 'Hibberd, Martin L.']",,,,
,PMC,Best Practice No 175: Guidelines for virological and non-viral serological examination of specimens in routine diagnostic microbiological laboratories,,PMC1770154,,,"Viral examination is routinely carried out in most routine diagnostic microbiology laboratories. Most often, this comprises the detection of viral antigens and antibodies, and less commonly the isolation of viruses and the detection of viral nucleic acids. However, there are no standards or guidelines available for processing these specimens in routine diagnostic laboratories or for referral to specialist virology centres or units. Clinical Pathology Accreditation (CPA) has defined standards for assessing the quality of service provided by laboratories, but these do not include the scientific and technical aspects of provision of service. The Association of Medical Microbiologists has recently published Standards for Laboratory practice in medical microbiology, which covers scientific and technical aspects of provision of microbiology service, mainly bacteriological examination of specimens in routine diagnostic microbiology laboratories. These guidelines are complementary to the CPA guidelines and aim to ensure a consistent and high quality service. This article presents guidelines for the examination of specimens for the diagnosis of viral infections.",,"['Francis, J', 'Barrett, S P', 'Ogilvie, M M', 'Sutherland, S']",,,,
,PMC,GFSWeb: A web tool for genome-based identification of proteins from mass spectrometric samples,http://dx.doi.org/10.1021/pr049879y,PMC1351070,,,"The interpretation of mass spectrometry data for protein identification has become a vital component of proteomics research. However, since most existing software tools rely on protein databases, their success is limited, especially as the pace of annotation efforts fails to keep pace with sequencing. We present a publicly available, web-based version of a software tool that maps peptide mass fingerprint data directly to their genomic origin, allowing for genome-based, annotation-independent protein identification.",,"['Wisz, Michael S.', 'Suarez, Melissa Kimball', 'Holmes, Mark R.', 'Giddings, Morgan C.']",,,,
,PMC,CXC Chemokine Ligand 10 Controls Viral Infection in the Central Nervous System: Evidence for a Role in Innate Immune Response through Recruitment and Activation of Natural Killer Cells,http://dx.doi.org/10.1128/JVI.78.2.585-594.2004,PMC368822,,,"How chemokines shape the immune response to viral infection of the central nervous system (CNS) has largely been considered within the context of recruitment and activation of antigen-specific lymphocytes. However, chemokines are expressed early following viral infection, suggesting an important role in coordinating innate immune responses. Herein, we evaluated the contributions of CXC chemokine ligand 10 (CXCL10) in promoting innate defense mechanisms following coronavirus infection of the CNS. Intracerebral infection of RAG1(−/−) mice with a recombinant CXCL10-expressing murine coronavirus (mouse hepatitis virus) resulted in protection from disease and increased survival that correlated with a significant increase in recruitment and activation of natural killer (NK) cells within the CNS. Accumulation of NK cells resulted in a reduction in viral titers that was dependent on gamma interferon secretion. These results indicate that CXCL10 expression plays a pivotal role in defense following coronavirus infection of the CNS by enhancing innate immune responses.",,"['Trifilo, Matthew J.', 'Montalto-Morrison, Cynthia', 'Stiles, Linda N.', 'Hurst, Kelley R.', 'Hardison, Jenny L.', 'Manning, Jerry E.', 'Masters, Paul S.', 'Lane, Thomas E.']",,,,
,PMC,Sequence Motifs Involved in the Regulation of Discontinuous Coronavirus Subgenomic RNA Synthesis,http://dx.doi.org/10.1128/JVI.78.2.980-994.2004,PMC368802,,,"Coronavirus transcription leads to the synthesis of a nested set of mRNAs with a leader sequence derived from the 5′ end of the genome. The mRNAs are produced by a discontinuous transcription in which the leader is linked to the mRNA coding sequences. This process is regulated by transcription-regulating sequences (TRSs) preceding each mRNA, including a highly conserved core sequence (CS) with high identity to sequences present in the virus genome and at the 3′ end of the leader (TRS-L). The role of TRSs was analyzed by reverse genetics using a full-length infectious coronavirus cDNA and site-directed mutagenesis of the CS. The canonical CS-B was nonessential for the generation of subgenomic mRNAs (sgmRNAs), but its presence led to transcription levels at least 10(3)-fold higher than those in its absence. The data obtained are compatible with a transcription mechanism including three steps: (i) formation of 5′-3′ complexes in the genomic RNA, (ii) base-pairing scanning of the nascent negative RNA strand by the TRS-L, and (iii) template switching during synthesis of the negative strand to complete the negative sgRNA. This template switch takes place after copying the CS sequence and was predicted in silico based on high base-pairing score between the nascent negative RNA strand and the TRS-L and minimum ΔG.",,"['Zúñiga, Sonia', 'Sola, Isabel', 'Alonso, Sara', 'Enjuanes, Luis']",,,,
,PMC,Characterization of the RNA Components of a Putative Molecular Switch in the 3′ Untranslated Region of the Murine Coronavirus Genome,http://dx.doi.org/10.1128/JVI.78.2.669-682.2004,PMC368785,,,"RNA virus genomes contain cis-acting sequence and structural elements that participate in viral replication. We previously identified a bulged stem-loop secondary structure at the upstream end of the 3′ untranslated region (3′ UTR) of the genome of the coronavirus mouse hepatitis virus (MHV). This element, beginning immediately downstream of the nucleocapsid gene stop codon, was shown to be essential for virus replication. Other investigators discovered an adjacent downstream pseudoknot in the 3′ UTR of the closely related bovine coronavirus (BCoV). This pseudoknot was also shown to be essential for replication, and it has a conserved counterpart in every group 1 and group 2 coronavirus. In MHV and BCoV, the bulged stem-loop and pseudoknot are, in part, mutually exclusive, because of the overlap of the last segment of the stem-loop and stem 1 of the pseudoknot. This led us to hypothesize that they form a molecular switch, possibly regulating a transition occurring during viral RNA synthesis. We have now performed an extensive genetic analysis of the two components of this proposed switch. Our results define essential and nonessential components of these structures and establish the limits to which essential parts of each element can be destabilized prior to loss of function. Most notably, we have confirmed the interrelationship of the two putative switch elements. Additionally, we have identified a pseudoknot loop insertion mutation that appears to point to a genetic interaction between the pseudoknot and a distant region of the genome.",,"['Goebel, Scott J.', 'Hsue, Bilan', 'Dombrowski, Todd F.', 'Masters, Paul S.']",,,,
,PMC,N-Terminal Domain of the Murine Coronavirus Receptor CEACAM1 Is Responsible for Fusogenic Activation and Conformational Changes of the Spike Protein,http://dx.doi.org/10.1128/JVI.78.1.216-223.2004,PMC303413,,,"The mouse hepatitis virus (MHV) receptor (MHVR), CEACAM1, has two different functions for MHV entry into cells: binding to MHV spike protein (S protein) and activation of the S protein to execute virus-cell membrane fusion, the latter of which is accompanied by conformational changes of the S protein. The MHVR comprising the N-terminal and fourth domains [R1(1,4)] displays these two activities, and the N domain is thought to be critical for binding to MHV. In this study, we have addressed whether or not the N domain alone is sufficient for these activities. We examined three types of soluble form MHVR (soMHVR), one consisting of the N domain alone [soR1(1)], one with the N and second domains [soR1(1,2)], and one [soR1(1,4)] expressed by recombinant baculoviruses. We assessed the abilities of these three types of soMHVR to bind to MHV, activate fusogenicity, and induce conformational changes of the S protein. All three types of soMHVR similarly bound to MHV, as examined by a solid-phase binding assay and neutralized MHV infectivity. They also activated S protein fusogenicity and induced its conformational changes with similar levels of efficiency. However, R1(1) expressed on the BHK cell surface failed to serve as a receptor in spite of a sufficient level of expression. The inability of expressed R1(1) to work as a receptor was due to the inaccessibility of virions to R1(1); however, these were accessible using the MHVR-specific monoclonal antibody CC1. These results collectively indicated that the N domain retains all biological activities necessary for receptor function.",,"['Miura, Hideka S.', 'Nakagaki, Keiko', 'Taguchi, Fumihiro']",,,,
,PMC,Inefficient Signalase Cleavage Promotes Efficient Nucleocapsid Incorporation into Budding Flavivirus Membranes,http://dx.doi.org/10.1128/JVI.78.1.178-186.2004,PMC303399,,,"The mechanism for efficient nucleocapsid (NC) uptake into flavivirus particles which form by budding through the membranes of the endoplasmic reticulum (ER) was investigated by using Murray Valley encephalitis virus as a model. Budding of flavivirus membranes is driven by the viral transmembrane proteins prM and E independently of NC interaction. We show that control of signalase cleavage of the multimembrane-spanning flavivirus polyprotein by the catalytic function of the viral protease is critical for efficient virus morphogenesis. In wild-type virus, signalase cleavage of prM remains inefficient until cleavage of capsid at the cytosolic side of the signal sequence separating the two proteins has occurred. This obligatory sequence of cleavages was uncoupled in a mutant virus with the consequence of greatly reduced incorporation of NC into budding membranes and augmented release of NC-free virus-like particles. Efficient signalase cleavage of prM in the mutant virus resulted in partial inhibition of cleavage of capsid by the viral NS2B-3 protease. Our results support a model for flavivirus morphogenesis involving temporal and spatial coordination of NC assembly and envelopment by regulated cleavages of an ER membrane-spanning capsid-prM intermediate.",,"['Lobigs, Mario', 'Lee, Eva']",,,,
,PMC,Mosaic Evolution of the Severe Acute Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1128/JVI.78.1.76-82.2004,PMC303383,,,"Severe acute respiratory syndrome (SARS) is a deadly form of pneumonia caused by a novel coronavirus, a viral family responsible for mild respiratory tract infections in a wide variety of animals including humans, pigs, cows, mice, cats, and birds. Analyses to date have been unable to identify the precise origin of the SARS coronavirus. We used Bayesian, neighbor-joining, and split decomposition phylogenetic techniques on the SARS virus replicase, surface spike, matrix, and nucleocapsid proteins to reveal the evolutionary origin of this recently emerging infectious agent. The analyses support a mammalian-like origin for the replicase protein, an avian-like origin for the matrix and nucleocapsid proteins, and a mammalian-avian mosaic origin for the host-determining spike protein. A bootscan recombination analysis of the spike gene revealed high nucleotide identity between the SARS virus and a feline infectious peritonitis virus throughout the gene, except for a 200- base-pair region of high identity to an avian sequence. These data support the phylogenetic analyses and suggest a possible past recombination event between mammalian-like and avian-like parent viruses. This event occurred near a region that has been implicated to be the human receptor binding site and may have been directly responsible for the switch of host of the SARS coronavirus from animals to humans.",,"['Stavrinides, John', 'Guttman, David S.']",,,,
,PMC,VirGen: a comprehensive viral genome resource,http://dx.doi.org/10.1093/nar/gkh098,PMC308832,,,"VirGen is a comprehensive viral genome resource that organizes the ‘sequence space’ of viral genomes in a structured fashion. It has been developed with the objective of serving as an annotated and curated database comprising complete genome sequences of viruses, value-added derived data and data mining tools. The current release (v1.1) contains 559 complete genomes in addition to 287 putative genomes of viruses belonging to eight viral families for which the host range includes animals and plants. Viral genomes in VirGen are annotated using sequence-based Bioinformatics approaches. The genomic data is also curated to identify ‘alternate names’ of viral proteins, where available. VirGen archives the results of comparisons of genomes, proteomes and individual proteins within and between viral species. It is the first resource to provide phylogenetic trees of viral species computed using whole-genome sequence data. The module of predicted B-cell antigenic determinants in VirGen is an attempt to link the genome to its vaccinome. Comparative genome analysis data facilitate the study of genome organization and evolution of viruses, which would have implications in applied research to identify candidates for the design of vaccines and antiviral drugs. VirGen is a relational database and is available at http://bioinfo.ernet.in/virgen/virgen.html.",,"['Kulkarni-Kale, Urmila', 'Bhosle, Shriram', 'Manjari, G. Sunitha', 'Kolaskar, A. S.']",,,,
,PMC,Database resources of the National Center for Biotechnology Information: update,http://dx.doi.org/10.1093/nar/gkh073,PMC308807,,,"In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval resources for the data in GenBank and other biological data made available through NCBI’s website. NCBI resources include Entrez, PubMed, PubMed Central, LocusLink, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosome Aberration Project (CCAP), Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups (COGs) database, Retroviral Genotyping Tools, SARS Coronavirus Resource, SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man (OMIM), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD) and the Conserved Domain Architecture Retrieval Tool (CDART). Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at: http://www.ncbi.nlm.nih.gov.",,"['Wheeler, David L.', 'Church, Deanna M.', 'Edgar, Ron', 'Federhen, Scott', 'Helmberg, Wolfgang', 'Madden, Thomas L.', 'Pontius, Joan U.', 'Schuler, Gregory D.', 'Schriml, Lynn M.', 'Sequeira, Edwin', 'Suzek, Tugba O.', 'Tatusova, Tatiana A.', 'Wagner, Lukas']",,,,
,PMC,Severe acute respiratory syndrome (SARS),,PMC1757795,,,,,"Wong, O",,,,
,PMC,The quarantine war: the burning of the New York Marine Hospital in 1858.,http://dx.doi.org/10.1016/j.phr.2004.03.014,PMC1502261,,,,,"Stephenson, Kathryn",,,,
,PMC,Industry and Government Perspective in Influenza Control,,PMC387432,,,"We have had recent reminders of the threats posed by naturally occurring and bioengineered pandemic respiratory infections. It is estimated that if a pandemic infection were to arise anywhere in the world, such an infection would become widespread within 3 months and would have its maximum effect within 6 months. At present, the fastest that a vaccine effective against a new combination of antigens can be developed, purified, and produced is 9–12 months, not counting time for mass production. The current rate at which the production of influenza vaccines can be accelerated is limited by the fact that production is carried out in eggs. Therefore, there is urgent need for cell-based vaccine technologies. These are under way in several centers, yet attainment of a safe product remains several years away. Furthermore, there is need for public and private investment in manufacturing surge capacity and/or dedicated National Institutes of Health facilities to enable accelerated production. We must support efforts to shorten development time by developing and approving subunit antigens and immunogens that anticipate the most virulent viral mutations. Surveillance sites and their electronic interconnections must be expanded. Another component still lacking is funding for laboratories with high throughput screening and strong informatics capabilities to enable the fingerprinting and cataloguing of all known specimens of influenza and other pathogenic organisms for rapid identification of emerging or bioengineered pathogens. In all these efforts, we look to the federal government and to the biomedical research community in both public and private sectors.",,"Slater, Eve E.",,,,
,PMC,SARS: An Emerging Global Microbial Threat.,,PMC2263793,,,"In March 2003, the Institute of Medicine published an update to its 1992 landmark report on emerging infections. The new report, Microbial Threats to Health: Emergence, Detection, and Response, describes the current spectrum of global microbial threats, factors affecting their emergence or resurgence, and measures that should be undertaken to effectively address them. Coincident with this publication came increasing reports of severe atypical pneumonia of unknown etiology among persons in southeast Asia. This new disease, designated severe acute respiratory syndrome (SARS), spread globally in a matter of weeks, infecting primarily close contacts of index patients (e.g., household members and healthcare workers caring for index patients) but also resulting in community transmission in some areas. An unprecedented worldwide collaborative effort was undertaken to determine the cause of the illness and implement prevention measures. A previously unrecognized coronavirus was identified as the causative agent, and health officials throughout the world struggled to implement measures to contain its spread, including isolation of suspect SARS cases and quarantine of exposed persons. The emergence of SARS is a timely reminder of the need to expect the unexpected and to ensure strong national and global public health partnerships when preparing for and responding to infectious diseases. Effectively addressing the threat of SARS will require enhanced global infectious disease surveillance, the development of rapid diagnostics, new therapies, and vaccines, implementation of aggressive evidence-based infection control strategies, and effective communication.",,"Hughes, James M.",,,,
,PMC,Houston biosecurity: building a national model.,,PMC2263787,,,"On September 11, 2001, Al Qaeda terrorists committed an atrocity when they used domestic jetliners to crash into buildings in New York City and Washington, DC, killing thousands of people. In October 2001, another act of savagery occurred, this time using anthrax, not airplanes, to take innocent lives. Each incident demonstrates the vulnerability of an open society, and Americans are left to wonder how such acts can be prevented. Two years later, Al Qaeda operatives are reportedly regrouping, recruiting, and changing their tactics to distribute money and messages to operatives around the world. Many experts believe that terrorist attacks are inevitable. Every city is vulnerable to an attack, and none are fully prepared to handle the residual impact of a biological or chemical attack. A survey conducted by the Cable News Network (CNN) in January 2002, studied 30 major US cities, ranking them based on 6 statistical indices of vulnerability. Thirteen cities were deemed better prepared than Houston, 10 were in a similar state of preparedness, and only 6 were less prepared than Houston. We will discuss the protective measures that have been put in place in Houston, and future steps to take. Other cities can model Houston's experience to develop similar plans nation-wide.",,"['Casscells, Ward', 'Mirhaji, Parsa', 'Lillibridge, Scott', 'Madjid, Mohammad']",,,,
,PMC,Contact tracing and disease control.,http://dx.doi.org/10.1098/rspb.2003.2554,PMC1691540,,,"Contact tracing, followed by treatment or isolation, is a key control measure in the battle against infectious diseases. It is an extreme form of locally targeted control, and as such has the potential to be highly efficient when dealing with low numbers of cases. For this reason it is frequently used to combat sexually transmitted diseases and new invading pathogens. Accurate modelling of contact tracing requires explicit information about the disease-transmission pathways from each individual, and hence the network of contacts. Here, pairwise-approximation methods and full stochastic simulations are used to investigate the utility of contact tracing. A simple relationship is found between the efficiency of contact tracing necessary for eradication and the basic reproductive ratio of the disease. This holds for a wide variety of realistic situations including heterogeneous networks containing core-groups or super-spreaders, and asymptomatic individuals. Clustering (transitivity) within the transmission network is found to destroy the relationship, requiring lower efficiency than predicted.",,"['Eames, Ken T D', 'Keeling, Matt J']",,,,
,PMC,Molecular model of SARS coronavirus polymerase: implications for biochemical functions and drug design,http://dx.doi.org/10.1093/nar/gkg916,PMC291860,,,"The causative agent of severe acute respiratory syndrome (SARS) is a previously unidentified coronavirus, SARS-CoV. The RNA-dependent RNA polymerase (RdRp) of SARS-CoV plays a pivotal role in viral replication and is a potential target for anti-SARS therapy. There is a lack of structural or biochemical data on any coronavirus polymerase. To provide insights into the structure and function of SARS-CoV RdRp, we have located its conserved motifs that are shared by all RdRps, and built a three-dimensional model of the catalytic domain. The structural model permits us to discuss the potential functional roles of the conserved motifs and residues in replication and their potential interactions with inhibitors of related enzymes. We predict important structural attributes of potential anti-SARS-CoV RdRp nucleotide analog inhibitors: hydrogen-bonding capability for the 2′ and 3′ groups of the sugar ring and C3′ endo sugar puckering, and the absence of a hydrophobic binding pocket for non-nucleoside analog inhibitors similar to those observed in hepatitis C virus RdRp and human immunodeficiency virus type 1 reverse transcriptase. We propose that the clinically observed resistance of SARS to ribavirin is probably due to perturbation of the conserved motif A that controls rNTP binding and fidelity of polymerization. Our results suggest that designing anti-SARS therapies can benefit from successful experiences in design of other antiviral drugs. This work should also provide guidance for future biochemical experiments.",,"['Xu, Xiang', 'Liu, Yunqing', 'Weiss, Susan', 'Arnold, Eddy', 'Sarafianos, Stefan G.', 'Ding, Jianping']",,,,
,PMC,Real time assay of Aspergillus should be used in SARS patients receiving corticosteroids,,PMC293004,,,,,"['Wu, Ya Ping', 'Wei, Ran', 'Verhoef, Jan']",,,,
,PMC,"Systematic, genome-wide identification of host genes affecting replication of a positive-strand RNA virus",http://dx.doi.org/10.1073/pnas.2536857100,PMC307642,,,"Positive-strand RNA viruses are the largest virus class and include many pathogens such as hepatitis C virus and the severe acute respiratory syndrome coronavirus (SARS). Brome mosaic virus (BMV) is a representative positive-strand RNA virus whose RNA replication, gene expression, and encapsidation have been reproduced in the yeast Saccharomyces cerevisiae. By using traditional yeast genetics, host genes have been identified that function in controlling BMV translation, selecting BMV RNAs as replication templates, activating the replication complex, maintaining a lipid composition required for membrane-associated RNA replication, and other steps. To more globally and systematically identify such host factors, we used engineered BMV derivatives to assay viral RNA replication in each strain of an ordered, genome-wide set of yeast single-gene deletion mutants. Each deletion strain was transformed to express BMV replicase proteins and a BMV RNA replication template with the capsid gene replaced by a luciferase reporter. Luciferase expression, which is dependent on viral RNA replication and RNA-dependent mRNA synthesis, was measured in intact yeast cells. Approximately 4,500 yeast deletion strains (≈80% of yeast genes) were screened in duplicate and selected strains analyzed further. This functional genomics approach revealed nearly 100 genes whose absence inhibited or stimulated BMV RNA replication and/or gene expression by 3- to >25-fold. Several of these genes were shown previously to function in BMV replication, validating the approach. Newly identified genes include some in RNA, protein, or membrane modification pathways and genes of unknown function. The results further illuminate virus and cell pathways. Further refinement of virus screening likely will reveal contributions from additional host genes.",,"['Kushner, David B.', 'Lindenbach, Brett D.', 'Grdzelishvili, Valery Z.', 'Noueiry, Amine O.', 'Paul, Scott M.', 'Ahlquist, Paul']",,,,
,PMC,Worry,,PMC280584,,,,,"Ruskin, Ronald",,,,
,PMC,My experience with SARS,,PMC280583,,,,,"Cheung, C. Mark",,,,
,PMC,The new normal: a SARS diary,,PMC280582,,,,,"Greiver, Michelle",,,,
,PMC,,,PMC286345,,,,,,,,,
,PMC,Ethics and SARS: lessons from Toronto,,PMC286332,,,The SARS epidemic showed how easy it is for infectious diseases to spread round the world. Ethical as well as clinical issues need to be resolved to improve the response to the next epidemic,,"['Singer, Peter A', 'Benatar, Solomon R', 'Bernstein, Mark', 'Daar, Abdallah S', 'Dickens, Bernard M', 'MacRae, Susan K', 'Upshur, Ross E G', 'Wright, Linda', 'Shaul, Randi Zlotnik']",,,,
,PMC,Public Health in China: The Shanghai CDC Perspective,,PMC1448136,,,,,"['Peng, Jing', 'Zhang, Sheng Nian', 'Lu, Wei', 'Chen, Andrew T. L.']",,,,
,PMC,Detection of leptospirosis in India,http://dx.doi.org/10.1136/adc.88.12.1033,PMC1719381,,,,,"Vinetz, J",,,,
,PMC,Safety of herbal medicines in children,http://dx.doi.org/10.1136/adc.88.12.1032,PMC1719375,,,,,"Choonara, I",,,,
,PMC,Porcine peripheral blood dendritic cells and natural interferon-producing cells,http://dx.doi.org/10.1111/j.1365-2567.2003.01755.x,PMC1783075,,,"Peripheral blood contains two major particular infrequent dendritic cells (DC) subsets linking the innate and specific immune system, the myeloid DC and plasmacytoid DC equivalent to the natural interferon-producing cells (NIPC). The functional characterization of these cells demands large volumes of blood, making a large animal model more appropriate and beneficial for certain studies. Here, two subsets of porcine blood mononuclear cells expressing swine workshop cluster 3 (SWC3, a SIRP family member), are described and compared to monocytes. The blood DC specialized in T-cell stimulation were major histocompatibility complex (MHC) class II(+), CD80/86(+), CD1(+/–), CD4(−), and in contrast to monocytes CD14(−). A CD16(−) and a CD16(+) subset could be discriminated. Granulocyte–macrophage colony-stimulating factor and interleukin-3 were survival factors for this DC subset, and culture induced an up-regulation of MHC class II and CD80/86. The second subset described, are porcine NIPC, typically CD4(++), MHC class II(low), CD80/86(low), CD1(−), CD8(−/low), CD16(−/low) and CD45RA(−/low). Porcine NIPC had high interleukin-3 binding capacity, and survived in response to this cytokine. Their unique function was strong interferon type I secretion after virus stimulation. Both subsets were endocytically active when freshly isolated, and down-regulated this activity after in vitro maturation. Taken together, the present report has delineated porcine blood DC and NIPC, permitting a more detailed understanding of innate immune defences, particularly in response to infections.",,"['Summerfield, Artur', 'Guzylack-Piriou, Laurence', 'Schaub, Alexander', 'Carrasco, Carlos P', 'Tâche, Valerie', 'Charley, Bernard', 'McCullough, Kenneth C']",,,,
,PMC,Diagnosis of Severe Acute Respiratory Syndrome (SARS) by Detection of SARS Coronavirus Nucleocapsid Antibodies in an Antigen-Capturing Enzyme-Linked Immunosorbent Assay,http://dx.doi.org/10.1128/JCM.41.12.5781-5782.2003,PMC309018,,,"Recombinant severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein was employed to establish an antigen-capturing enzyme-linked immunosorbent assay (ELISA). Antinucleocapsid protein antibodies could be detected in 68.4% of probable SARS patients 6 to 10 days after illness and in 89.6% of the patients 11 to 61 days after illness. No false-positive results were observed in 20 non-SARS fever patients, 24 non-SARS respiratory illness patients, and 20 health care workers. Among 940 other non-SARS clinical serum samples, only 1 was found to be weakly positive. This method provides a new, sensitive, and specific approach for SARS diagnosis.",,"['Shi, Yuling', 'Yi, Yanping', 'Li, Ping', 'Kuang, Tieji', 'Li, Linhai', 'Dong, Mei', 'Ma, Qingjun', 'Cao, Cheng']",,,,
,PMC,How would schools step up public health measures to control spread of SARS?,http://dx.doi.org/10.1136/jech.57.12.945,PMC1732341,,,"The severe acute respiratory syndrome (SARS) is a rapidly progressive, and sometime fatal disease with more than 1800 patients in over a dozen countries in Asia, Europe, and North America (including the United States and Canada) within two months. On 12 March 2003, the World Health Organisation (WHO) issued a global alert about SARS so it became a global challenge. Strengthening the public health measures at schools would protect children as well as providing the students an opportunity to learn about infectious disease control through life event approach. The public health measures at schools include two important components: basic understanding of the disease so schools would put on high alert on caution cases, and the measures to improve environmental hygiene at schools and preventive measures to stop infectious disease transmission. This will help to empower the whole community the readiness to deal with other outbreaks in the future.",,"['Lee, A', 'Cheng, F', 'Yuen, H', 'Ho, M']",,,,
,PMC,Neutralization of Enteric Coronaviruses with Escherichia coli Cells Expressing Single-Chain Fv-Autotransporter Fusions,http://dx.doi.org/10.1128/JVI.77.24.13396-13398.2003,PMC296075,,,We report here that fusions of single-chain antibodies (scFvs) to the autotransporter β domain of the IgA protease of Neisseria gonorrhoeae are instrumental in locating virus-neutralizing activity on the cell surface of Escherichia coli. E. coli cells displaying scFvs against the transmissible gastroenteritis coronavirus on their surface blocked in vivo the access of the infectious agent to cultured epithelial cells. This result raises prospects for antiviral strategies aimed at hindering the entry into target cells by bacteria that naturally colonize the same intestinal niches.,,"['Veiga, Esteban', 'de Lorenzo, Víctor', 'Fernández, Luis Angel']",,,,
,PMC,Bioprospecting for Microbial Endophytes and Their Natural Products,http://dx.doi.org/10.1128/MMBR.67.4.491-502.2003,PMC309047,,,"Endophytic microorganisms are to be found in virtually every plant on earth. These organisms reside in the living tissues of the host plant and do so in a variety of relationships, ranging from symbiotic to slightly pathogenic. Because of what appears to be their contribution to the host plant, the endophytes may produce a plethora of substances of potential use to modern medicine, agriculture, and industry. Novel antibiotics, antimycotics, immunosuppressants, and anticancer compounds are only a few examples of what has been found after the isolation, culture, purification, and characterization of some choice endophytes in the recent past. The potential prospects of finding new drugs that may be effective candidates for treating newly developing diseases in humans, plants, and animals are great.",,"['Strobel, Gary', 'Daisy, Bryn']",,,,
,PMC,The SARS outbreak and community paediatrics,,PMC2795282,,,,,"Tolkin, Jonathan",,,,
,PMC,Community-acquired pneumonia in children,,PMC2795279,,,"Community acquired pneumonia (CAP) is common in childhood. Viruses account for most cases of CAP during the first two years of life. After this period, bacteria such as Streptococcus pneumoniae, Mycoplasma pneumoniae and Chlamydia pneumoniae become more frequent. CAP symptoms are nonspecific in younger infants, but cough and tachypnea are usually present in older children. Chest x-ray is useful for confirming the diagnosis. Most children can be managed empirically with oral antibiotics as outpatients without specific laboratory investigations. Those with severe infections or with persistent or worsening symptoms need more intensive investigations and may need admission to hospital. The choice and dosage of antibiotics should be based on the age of the patient, severity of the pneumonia and knowledge of local antimicrobial resistance patterns. The Canadian Paediatric Society recommends the use of the heptavalent conjugate pneumococcal vaccine, which is efficacious in reducing chest x-ray positive pneumonia by up to 20%.",,"Davies, H Dele",,,,
,PMC,"For coughs, colds and SARS, wear a mask",,PMC2795275,,,,,"Scheifele, David",,,,
,PMC,SARS and the maternal neonatal unit,,PMC2795274,,,,,"['Whyte, Hilary', 'Tai, Kin Fan Young', 'Dunn, Michael']",,,,
,PMC,Metapneumovirus and its place in childhood,,PMC2795268,,,"Human metapneumovirus (hMPV) was recently identified as a cause of acute upper and lower respiratory tract infection in children and adults. The epidemiology is similar to that exhibited by respiratory syncytial virus, with most episodes occurring during the winter months. The virus likely has a worldwide distribution. Almost all children have been infected by five years of age. The suspicion of hMPV infection should be higher in infants or children presenting with symptoms compatible with a viral etiology and in whom screening tests for other common viral pathogens have been negative. Clinical manifestations may be subtle or severe, including life-threatening bronchiolitis or pneumonia. Fever, rhinorrhea, cough, retractions, tachypnea and wheezing are common findings. Bronchiolitis is perhaps the most common manifestation among hospitalized children. Currently, there is no antiviral treatment or vaccine available and management is simply supportive.",,"Ulloa-Gutierrez, Rolando",,,,
,PMC,Smallpox and bioterrorism.,,PMC2572332,,,"Smallpox was declared to be eradicated on 8 May 1980, during the Thirty-third World Health Assembly. However, concerns about the possible use of the virus as a weapon of bioterrorism have increased in recent years. Governments have responded by initiating selective vaccination programmes and other public health measures. This review uses historical data from 20th century outbreaks to assess the risks to current populations (which have declining immunity) from a deliberate release of virus. The data presented supports the conclusion of a previous reviewer (Mack) that ""smallpox cannot be said to live up to its reputation. Far from being a quick-footed menace, it has appeared as a plodding nuisance with more bark than bite."" Its R value (the average number of secondary cases infected by a primary case) is lower than that for measles, human parvovirus, chickenpox, mumps, rubella, and poliomyelitis; only the value for severe acute respiratory syndrome (SARS) is lower. Like SARS, close person-to-person contact is required for effective spread of the disease, and exposure to the virus in hospitals has played an important role in transmission for both viruses. In the present paper the dangers of mass vaccination are emphasized, along with the importance of case isolation, contact tracing, and quarantine of close contacts for outbreak control. The need for rapid diagnosis and the continued importance of maintaining a network of electron microscopes for this purpose are also highlighted.",,"Pennington, Hugh",,,,
,PMC,Antiviral treatment of SARS: Can we draw any conclusions?,,PMC264956,,,,,"Zhaori, Getu",,,,
,PMC,SARS in health care workers,,PMC264945,,,,,"Farrow, Gordon",,,,
,PMC,Highlights of this issue,,PMC264938,,,,,,,,,
,PMC,In brief,,PMC261804,,,,,,,,,
,PMC,SARS war: combating the disease,,PMC259137,,,,,"Saiman, Lisa",,,,
,PMC,SURVEY AND SUMMARY: Roles of 5-substituents of tRNA wobble uridines in the recognition of purine-ending codons,http://dx.doi.org/10.1093/nar/gkg839,PMC275538,,,"Many tRNA molecules that recognize the purine-ending codons but not the pyrimidine-ending codons have a modified uridine at the wobble position, in which a methylene carbon is attached directly to position 5 of the uracil ring. Although several models have been proposed concerning the mechanism by which the 5-substituents regulate codon-reading properties of the tRNAs, none could explain recent results of the experiments utilizing well-characterized modification-deficient strains of Escherichia coli. Here, we first summarize previous studies on the codon-reading properties of tRNA molecules with a U derivative at the wobble position. Then, we propose a hypothetical mechanism of the reading of the G-ending codons by such tRNA molecules that could explain the experimental results. The hypothesis supposes unconventional base pairs between a protonated form of the modified uridines and the G at the third position of the codon stabilized by two direct hydrogen bonds between the bases. The hypothesis also addresses differences between the prokaryotic and eukaryotic decoding systems.",,"['Takai, Kazuyuki', 'Yokoyama, Shigeyuki']",,,,
,PMC,Road traffic injuries--a neglected pandemic.,,PMC2572538,,,,,"Mohan, Dinesh",,,,
,PMC,"WHO lacks teeth on international health issues, says professor",,PMC1126854,,,,,"Eaton, Lynn",,,,
,PMC,Reframing HIV and AIDS,,PMC261752,,,Last month WHO declared the HIV/AIDS epidemic a global health emergency. Should governments go one step further and treat it as a disaster?,,"['Stabinski, Lara', 'Pelley, Karen', 'Jacob, Shevin T', 'Long, Jason M', 'Leaning, Jennifer']",,,,
,PMC,"An Outbreak of the Severe Acute Respiratory Syndrome: Predictors of Health Behaviors and Effect of Community Prevention Measures in Hong Kong, China",,PMC1448068,,,,,"['Tang, Catherine S. K.', 'Wong, Chi-yan']",,,,
,PMC,Characterization of a Lactococcus lactis Strain That Secretes a Major Epitope of Bovine Beta-Lactoglobulin and Evaluation of Its Immunogenicity in Mice,http://dx.doi.org/10.1128/AEM.69.11.6620-6627.2003,PMC262270,,,"Bovine β-lactoglobulin (Blg) is one of the major cow's milk allergens. Peptide 41-60 of Blg (Blg41-60) was described as a murine T-cell determinant and a murine, rat, and human immunoglobulin E (IgE) epitope. The aim of this study was the expression of Blg41-60 as a fusion protein in the food-grade bacterium Lactococcus lactis and the characterization of its immunogenicity in mice. We constructed a recombinant strain of L. lactis capable of inducible production and secretion of Blg41-60::Nuc, a fusion protein between Blg41-60 and the mature part of the staphylococcal nuclease (Nuc). The highest production yield of Blg41-60::Nuc (32.5 mg/liter) was reached 4 h after induction. At this time, up to 75% of Blg41-60::Nuc was secreted. When monoclonal antibodies specific for Blg41-60 were used, purified Blg41-60::Nuc and synthetic Blg41-60 exhibited very similar immunoreactivities. Subcutaneous coadministration of purified Blg41-60::Nuc and killed nonrecombinant L. lactis resulted in the induction of specific anti-Blg41-60 IgG2a and IgG1. The IgG1/IgG2a ratio and the lack of specific IgE suggest a Th1-type immune response, i.e., a nonallergic response. Similar administrations of the killed Blg41-60::Nuc-producing L. lactis strain did not elicit a specific immune response, whereas a transitory mucosal IgA-specific immune response was induced in mice after oral administration of the live Blg41-60::Nuc-producing L. lactis strain.",,"['Chatel, Jean-Marc', 'Nouaille, Sebastien', 'Adel-Patient, Karine', 'Le Loir, Yves', 'Boe, Herman', 'Gruss, Alexandra', 'Wal, Jean-Michel', 'Langella, Philippe']",,,,
,PMC,"Public health doctors ""hopeless"" at using media",,PMC261718,,,PR chief says they must learn how to present their stories,,"Ferriman, Annabel",,,,
,PMC,Witnesses,,PMC2094955,,,,,"Nicolle, Lindsay",,,,
,PMC,Immuno-Chromatographic Assay for Diagnosis of Feline Leukemia Virus Infection,http://dx.doi.org/10.1023/B:CYTO.0000039900.04798.d1,PMC3449601,,,"Feline leukemia virus (FeLV) infectious disease is one of feline infection diseases spreading broadly all over the world. For bedside diagnosis of FeLV infectious disease, an immuno-chromatographic assay was investigated. Five different monoclonal antibodies were developed against the major core protein FeLV-p27. Among them, the combination of FL6 and FL12, which had little epitopic overlap each other, showed the highest sensitivity with no cross-reaction to the other feline virus antigens when they were employed to the immuno-chromatographic assay. The system had a practical detection limit of 0.5 ng of FeLV-p27 per 0.1 ml of feline sera within 15 min. In comparison with clinical standard methods, the system gave rapidly and accurately the same diagnosis with neither false negative nor false positive. Moreover, it did not need any pretreatment of blood specimen.",,"['Eto, Nozomu', 'Yazaki-Takayama, Nobiko', 'Takayama, Yoshikazu', 'Yoshino-Nakamura, Tomoko', 'Kobayashi, Yukuharu']",,,,
,PMC,"SARS: experience from the emergency department, Tan Tock Seng Hospital, Singapore",http://dx.doi.org/10.1136/emj.20.6.501,PMC1726235,,,,,"Seow, E",,,,
,PMC,Conjunctiva-Upper Respiratory Tract Irrigation for Early Diagnosis of Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1128/JCM.41.11.5352.2003,PMC262542,,,,,"['Tong, Tommy R.', 'Lam, Bosco H.', 'Ng, Tak-keung', 'Lai, Sik-to', 'Tong, Matthew K.', 'Chau, Tai-nin']",,,,
,PMC,Capnocytophaga sp. Isolated from a Cat with Chronic Sinusitis and Rhinitis,http://dx.doi.org/10.1128/JCM.41.11.5321-5324.2003,PMC262471,,,"A Capnocytophaga sp. was inadvertently isolated from a cat with chronic sinusitis and rhinitis when cytopathic effects were observed in Crandall-Reese feline kidney cells that had been inoculated with oropharyngeal swab samples. Although Capnocytophaga spp. are of considerable zoonotic importance, their clinical relevance for dogs or cats has not been established. However, failure to do so may be attributed to the infrequent use of specialized isolation techniques that are required to grow Capnocytophaga spp. To our knowledge, successful isolation of these organisms from a cat with nasopharyngeal disease has not been reported.",,"['Frey, Erin', 'Pressler, Barrak', 'Guy, James', 'Pitulle, Christian', 'Breitschwerdt, Edward']",,,,
,PMC,The impact of community psychological responses on outbreak control for severe acute respiratory syndrome in Hong Kong,http://dx.doi.org/10.1136/jech.57.11.857,PMC1732323,,,"Objective: To examine the public's knowledge and perception of SARS and the extent to which various precautionary measures have been adopted. Design: Cross sectional survey. Setting: General population of Hong Kong at the height of the SARS outbreak (29 March to 6 April 2003). Participants: 1115 ethnic Chinese adults. Main results: Forty per cent did not recognise fomites as a possible mode of transmission whereas 55.1% believed that the infection could be transmitted airborne. A large proportion (30.1%) believed they were very or somewhat likely to contract SARS while only one quarter believed they were very likely to survive if they contracted the disease, benchmarked against an actual case fatality ratio of 2.8% at the time of the survey and 15%–20% according to current best estimates. Precautionary measures directed against person to person droplet spread were generally adopted by most while the prevention of transmission through fomites was not practised as frequently. Respondents with higher risk perceptions and a moderate level of anxiety were most likely to take comprehensive precautionary measures against the infection, as were older, female, more educated people as well as those with a positive contact history and SARS-like symptoms. Conclusions: The findings demonstrate that the promotion of protective personal health practices to interrupt the self sustaining transmission of the SARS virus in the community must take into account background perceptions of risk and anxiety levels of the public at large. Continuing public education about preventive measures should be targeted at the identified groups with low current uptake of precautions.",,"['Leung, G', 'Lam, T', 'Ho, L', 'Ho, S', 'Chan, B', 'Wong, I', 'Hedley, A']",,,,
,PMC,Monitoring community responses to the SARS epidemic in Hong Kong: from day 10 to day 62,http://dx.doi.org/10.1136/jech.57.11.864,PMC1732318,,,"Study Objective: To report the evolution in perceptions and behaviours of the general public in response to the severe acute respiratory syndrome (SARS) epidemic in Hong Kong. Design: Ten similar and sequential telephone surveys were conducted during outbreak of SARS, which are classified as belonging to the first and second phases of the epidemic. Setting: Hong Kong, China. Participants: 1397 Hong Kong residents between 18 and 60 years of age. Main outcome measures: Perceptions and behaviours to SARS and its prevention. Results: Most of the respondents believed that SARS could be transmitted via direct body contact and droplets. About half of respondents believed that SARS was curable, which increased in the initial phase and decreased in the second phase. Perceived chance of infection was low (9%) but fear of infection in public places was high (48%). Perceived efficacy of hygiene measures (wearing a mask: 82%, hand washing: 93%, and home disinfection: 75%) remained high in both phases and the perceived efficacy of avoiding crowded place, and using public transportation, etc, increased initially and decreased in the second phase. In parallel, use of the three hygiene measures increased significantly in the first phase and remained high for wearing a mask and washing hands in the second phase. Percentages of people avoiding crowded place and public transportation significantly increased initially and decreased in the second phase. Conclusion: SARS related perceptions and behaviours evolved rapidly during the epidemic and Hong Kong residents quickly adopted appropriate SARS prevention measures. Timely dissemination of information seems effective in public health crises management.",,"['Lau, J', 'Yang, X', 'Tsui, H', 'Kim, J']",,,,
,PMC,Will the severe acute respiratory syndrome epidemic recur?,http://dx.doi.org/10.1136/jech.57.11.840,PMC1732316,,,,,"['Carmo, E', 'Barreto, M']",,,,
,PMC,Behind the mask. Journey through an epidemic: some observations of contrasting public health responses to SARS,http://dx.doi.org/10.1136/jech.57.11.855,PMC1732315,,,"SARS has been called the first global epidemic of the 21st century and has been the cause of a massive and varied public health response in many countries of the world. This report describes observations made by two authors on a journey from Manchester in the United Kingdom to Chiang Mai in Thailand during the peak of global transmission. The public response to SARS, particularly characterised by the wearing of face masks, seemed to outstrip official guidance. Though of uncertain protective benefit, the wearing of masks may have contributed to the awareness of the collective and personal responsibility in combating infectious disease. Active and empowered involvement of the general public in implementing and cooperating with public health control measures supported by national and international authorities has clearly helped to bring SARS under control. The public health significance of such potent symbols as the face mask may be considered in strategies to tackle other emerging infections.",,"['Syed, Q', 'Sopwith, W', 'Regan, M', 'Bellis, M']",,,,
,PMC,Antibody-Mediated Protection against Cytotoxic T-Cell Escape in Coronavirus-Induced Demyelination,http://dx.doi.org/10.1128/JVI.77.22.11867-11874.2003,PMC254260,,,"C57BL/6 (B6) mice infected with mouse hepatitis virus (MHV) strain JHM develop a clinically evident, demyelinating encephalomyelitis. Infectious virus can be isolated from the spinal cords of these mice and is invariably mutated in the immunodominant CD8 T-cell epitope recognized in this strain. We showed previously that these persistently infected mice did not mount a measurable serum anti-MHV neutralizing antibody response. Here we show that cytotoxic T-lymphocyte (CTL) escape was not detected in MHV-infected BALB/b mice (H-2(b) haplotype), even though the same CD8 T-cell epitopes were recognized as in B6 mice. BALB/b mice had 25-fold more MHV-specific antibody-secreting cells in the central nervous system, the site of infection, than B6 mice, suggesting that local production of anti-MHV antibody contributed to this absence of CTL escape. Additionally, administration of anti-MHV neutralizing antibody to infected B6 mice suppressed the development of CTL escape mutants. These findings indicate a key role for the anti-MHV antibody response in suppressing virus replication, thereby minimizing the emergence and competitive advantage of CTL escape mutants.",,"['Dandekar, Ajai A.', 'Jacobsen, Gary', 'Waldschmidt, Thomas J.', 'Perlman, Stanley']",,,,
,PMC,Induction of Caspase-Dependent Apoptosis in Cultured Rat Oligodendrocytes by Murine Coronavirus Is Mediated during Cell Entry and Does Not Require Virus Replication,http://dx.doi.org/10.1128/JVI.77.22.11952-11963.2003,PMC254259,,,"Murine coronavirus mouse hepatitis virus (MHV) causes demyelination of the central nervous system (CNS) in rats and mice. Apoptotic oligodendrocytes have been detected in the vicinity of the CNS demyelinating lesions in these animals. However, whether MHV can directly induce oligodendrocyte apoptosis has not been documented. Here, we established a rat oligodendrocyte culture that is morphologically and phenotypically indistinguishable from the primary rat oligodendrocytes. Using this culture, we showed that mature rat oligodendrocytes were permissive to MHV infection but did not support productive virus replication. Significantly, oligodendrocytes infected with both live and ultraviolet light-inactivated viruses underwent apoptosis to a similar extent, which was readily detectable at 24 h postinfection as revealed by apoptotic bodies and DNA fragmentation, indicating that MHV-induced apoptosis is mediated during the early stages of the virus life cycle and does not require virus replication. Prior treatment of cells with the lysosomotropic agents NH(4)Cl and chloroquine as well as the vacuolar proton pump-ATPase inhibitor bafilomycin A1, all of which block the acidification of the endosome, prevented oligodendrocytes from succumbing to apoptosis induced by MHV mutant OBLV60, which enters cells via endocytosis, indicating that fusion between the viral envelope and cell membranes triggers the apoptotic cascade. Treatment with the pan-caspase inhibitor Z-VAD-fmk blocked MHV-induced apoptosis, suggesting an involvement of the caspase-dependent pathway. Our results, thus, for the first time provide unequivocal evidence that infection of oligodendrocytes with MHV directly results in apoptosis. This finding provides an explanation for the destruction of oligodendrocytes and the damage of myelin sheath in MHV-infected CNS and suggests that oligodendrocyte apoptosis may be one of the underlying mechanisms for the pathogenesis of MHV-induced demyelinating diseases in animals.",,"['Liu, Yin', 'Cai, Yingyun', 'Zhang, Xuming']",,,,
,PMC,Binding of Transmissible Gastroenteritis Coronavirus to Brush Border Membrane Sialoglycoproteins,http://dx.doi.org/10.1128/JVI.77.21.11846-11848.2003,PMC229351,,,"Transmissible gastroenteritis coronavirus (TGEV) is a porcine pathogen causing enteric infections that are lethal for suckling piglets. The enterotropism of TGEV is connected with the sialic acid binding activity of the viral surface protein S. Here we show that, among porcine intestinal brush border membrane proteins, TGEV recognizes a mucin-type glycoprotein designated MGP in a sialic acid-dependent fashion. Virus binding assays with cryosections of the small intestine from a suckling piglet revealed the binding of TGEV to mucin-producing goblet cells. A nonenteropathogenic mutant virus that lacked a sialic acid binding activity was unable to bind to MGP and to attach to goblet cells. Our results suggest a role of MGP in the enteropathogenicity of TGEV.",,"['Schwegmann-Wessels, Christel', 'Zimmer, Gert', 'Schröder, Bernd', 'Breves, Gerhard', 'Herrler, Georg']",,,,
,PMC,Two Distinct Size Classes of Immature and Mature Subviral Particles from Tick-Borne Encephalitis Virus,http://dx.doi.org/10.1128/JVI.77.21.11357-11366.2003,PMC229348,,,"Flaviviruses assemble in the endoplasmic reticulum by a mechanism that appears to be driven by lateral interactions between heterodimers of the envelope glycoproteins E and prM. Immature intracellular virus particles are then transported through the secretory pathway and converted to their mature form by cleavage of the prM protein by the cellular protease furin. Earlier studies showed that when the prM and E proteins of tick-borne encephalitis virus are expressed together in mammalian cells, they assemble into membrane-containing, icosahedrally symmetrical recombinant subviral particles (RSPs), which are smaller than whole virions but retain functional properties and undergo cleavage maturation, yielding a mature form in which the E proteins are arranged in a regular T = 1 icosahedral lattice. In this study, we generated immature subviral particles by mutation of the furin recognition site in prM. The mutation resulted in the secretion of two distinct size classes of particles that could be separated by sucrose gradient centrifugation. Electron microscopy showed that the smaller particles were approximately the same size as the previously described mature RSPs, whereas the larger particles were approximately the same size as the virus. Particles of the larger size class were also detected with a wild-type construct that allowed prM cleavage, although in this case the smaller size class was far more prevalent. Subtle differences in endoglycosidase sensitivity patterns suggested that, in contrast to the small particles, the E glycoproteins in the large subviral particles and whole virions might be in nonequivalent structural environments during intracellular transport, with a portion of them inaccessible to cellular glycan processing enzymes. These proteins thus appear to have the intrinsic ability to form alternative assembly products that could provide important clues about the role of lateral envelope protein interactions in flavivirus assembly.",,"['Allison, Steven L.', 'Tao, Yizhi J.', ""O'Riordain, Gabriel"", 'Mandl, Christian W.', 'Harrison, Stephen C.', 'Heinz, Franz X.']",,,,
,PMC,Coronaviruses as Vectors: Position Dependence of Foreign Gene Expression,http://dx.doi.org/10.1128/JVI.77.21.11312-11323.2003,PMC229330,,,"Coronaviruses are the enveloped, positive-stranded RNA viruses with the largest RNA genomes known. Several features make these viruses attractive as vaccine and therapeutic vectors: (i) deletion of their nonessential genes is strongly attenuating; (ii) the genetic space thus created allows insertion of foreign information; and (iii) their tropism can be modified by manipulation of the viral spike. We studied here their ability to serve as expression vectors by inserting two different foreign genes and evaluating systematically the genomic position dependence of their expression, using a murine coronavirus as a model. Renilla and firefly luciferase expression cassettes, each provided with viral transcription regulatory sequences (TRSs), were inserted at several genomic positions, both independently in different viruses and combined within one viral genome. Recombinant viruses were generated by using a convenient method based on targeted recombination and host cell switching. In all cases high expression levels of the foreign genes were observed without severe effects on viral replication in vitro. The expression of the inserted gene appeared to be dependent on its genomic position, as well as on the identity of the gene. Expression levels increased when the luciferase gene was inserted closer to the 3′ end of the genome. The foreign gene insertions generally reduced the expression of upstream viral genes. The results are consistent with coronavirus transcription models in which the transcription from upstream TRSs is attenuated by downstream TRSs. Altogether, our observations clearly demonstrate the potential of coronaviruses as (multivalent) expression vectors.",,"['de Haan, Cornelis A. M.', 'van Genne, Linda', 'Stoop, Jeroen N.', 'Volders, Haukeline', 'Rottier, Peter J. M.']",,,,
,PMC,Astrovirus Induces Diarrhea in the Absence of Inflammation and Cell Death,http://dx.doi.org/10.1128/JVI.77.21.11798-11808.2003,PMC229260,,,"Astroviruses are a leading cause of infantile viral gastroenteritis worldwide. Very little is known about the mechanisms of astrovirus-induced diarrhea. One reason for this is the lack of a small-animal model. Recently, we isolated a novel strain of astrovirus (TAstV-2) from turkeys with the emerging infectious disease poult enteritis mortality syndrome. In the present studies, we demonstrate that TAstV-2 causes growth depression, decreased thymus size, and enteric infection in infected turkeys. Infectious TAstV-2 can be recovered from multiple tissues, including the blood, suggesting that there is a viremic stage during infection. In spite of the severe diarrhea, histopathologic changes in the intestine were mild and there was a surprising lack of inflammation. This may be due to the increased activation of the potent immunosuppressive cytokine transforming growth factor beta during astrovirus infection. These studies suggest that the turkey will be a useful small-animal model with which to study astrovirus pathogenesis and immunity.",,"['Koci, Matthew D.', 'Moser, Lindsey A.', 'Kelley, Laura A.', 'Larsen, Diane', 'Brown, Corrie C.', 'Schultz-Cherry, Stacey']",,,,
,PMC,Severe acute respiratory syndrome (SARS),http://dx.doi.org/10.1136/thorax.58.11.919,PMC1746506,,,,,"['Muller, N', 'FitzGerald, J']",,,,
,PMC,The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor,http://dx.doi.org/10.1073/pnas.1835675100,PMC263746,,,"A newly identified severe acute respiratory syndrome coronavirus (SARS-CoV), is the etiological agent responsible for the outbreak of SARS. The SARS-CoV main protease, which is a 33.8-kDa protease (also called the 3C-like protease), plays a pivotal role in mediating viral replication and transcription functions through extensive proteolytic processing of two replicase polyproteins, pp1a (486 kDa) and pp1ab (790 kDa). Here, we report the crystal structures of the SARS-CoV main protease at different pH values and in complex with a specific inhibitor. The protease structure has a fold that can be described as an augmented serine-protease, but with a Cys-His at the active site. This series of crystal structures, which is the first, to our knowledge, of any protein from the SARS virus, reveal substantial pH-dependent conformational changes, and an unexpected mode of inhibitor binding, providing a structural basis for rational drug design.",,"['Yang, Haitao', 'Yang, Maojun', 'Ding, Yi', 'Liu, Yiwei', 'Lou, Zhiyong', 'Zhou, Zhe', 'Sun, Lei', 'Mo, Lijuan', 'Ye, Sheng', 'Pang, Hai', 'Gao, George F.', 'Anand, Kanchan', 'Bartlam, Mark', 'Hilgenfeld, Rolf', 'Rao, Zihe']",,,,
,PMC,WHO inquiry into SARS leaves questions unanswered,,PMC1140348,,,,,"Fleck, Fiona",,,,
,PMC,"Disseminated intravascular coagulation: old disease, new hope",,PMC259170,,,"Disseminated intravascular coagulation has long been associated with increased mortality in patients with sepsis. An effective treatment is now available, and the authors of this review describe how improved understanding and earlier diagnosis could lead to targeted treatment and improved prognosis",,"['Toh, Cheng Hock', 'Dennis, Michael']",,,,
,PMC,The virus hunter,,PMC259160,,,The scientist who helped to confirm the identity of the SARS virus is now asking countries to stockpile antiviral drugs in case of an influenza pandemic,,"Sheldon, Tony",,,,
,PMC,Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus,http://dx.doi.org/10.1073/pnas.1735582100,PMC240733,,,"A previously undescribed coronavirus (CoV) is the etiologic agent responsible for severe acute respiratory syndrome (SARS). Using a panel of contiguous cDNAs that span the entire genome, we have assembled a full-length cDNA of the SARS-CoV Urbani strain, and have rescued molecularly cloned SARS viruses (infectious clone SARS-CoV) that contained the expected marker mutations inserted into the component clones. Recombinant viruses replicated as efficiently as WT virus and both were inhibited by treatment with the cysteine proteinase inhibitor (2S,3S)-transepoxysuccinyl-l-leucylamido-3-methylbutane ethyl ester. In addition, subgenomic transcripts were initiated from the consensus sequence ACGAAC in both the WT and infectious clone SARS-CoV. Availability of a SARS-CoV full-length cDNA provides a template for manipulation of the viral genome, allowing for the rapid and rational development and testing of candidate vaccines and therapeutics against this important human pathogen.",,"['Yount, Boyd', 'Curtis, Kristopher M.', 'Fritz, Elizabeth A.', 'Hensley, Lisa E.', 'Jahrling, Peter B.', 'Prentice, Erik', 'Denison, Mark R.', 'Geisbert, Thomas W.', 'Baric, Ralph S.']",,,,
,PMC,Digital archive of Lancet is launched,,PMC1140359,,,,,"Ferriman, Annabel",,,,
,PMC,How SARS changed the world in less than six months.,,PMC2572529,,,,,"Fleck, Fiona",,,,
,PMC,"The Costa Rican health system: low cost, high value.",,PMC2572522,,,,,"Bertodano Id, Isabel de",,,,
,PMC,Canada's approach to public health must be reinvented: SARS report,,PMC203299,,,,,"Gandey, Allison",,,,
,PMC,New SARS recommendations to be released this month,,PMC203294,,,,,"Gandey, Allison",,,,
,PMC,Is it flu or SARS? MDs gear up for a difficult winter,,PMC203292,,,,,"Gandey, Allison",,,,
,PMC,A practical approach to airway management in patients with SARS,,PMC203281,,,,,"['Cooper, Andrew', 'Joglekar, Amit', 'Adhikari, Neill']",,,,
,PMC,Physician supply: future tense,,PMC203266,,,,,"Dawes, C.R.S.",,,,
,PMC,Word watch,,PMC203265,,,,,"['Schull, Michael J.', 'Redelmeier, Donald A.']",,,,
,PMC,Word watch,,PMC203264,,,,,"Pekeles, Gary",,,,
,PMC,"A Canadian agency for public health: If not now, when?",,PMC203262,,,,,,,,,
,PMC,Hong Kong hampered in fight against SARS by lack of cooperation from mainland,,PMC1140385,,,,,"Parry, Jane",,,,
,PMC,Curtailing transmission of severe acute respiratory syndrome within a community and its hospital.,http://dx.doi.org/10.1098/rspb.2003.2481,PMC1691475,,,"Severe acute respiratory syndrome (SARS) has been transmitted extensively within hospitals, and healthcare workers (HCWs) have comprised a large proportion of SARS cases worldwide. We present a stochastic model of a SARS outbreak in a community and its hospital. For a range of basic reproductive numbers (R(0)) corresponding to conditions in different cities (but with emphasis on R(0) approximately 3 as reported for Hong Kong and Singapore), we evaluate contact precautions and case management (quarantine and isolation) as containment measures. Hospital-based contact precautions emerge as the most potent measures, with hospital-wide measures being particularly important if screening of HCWs is inadequate. For R(0) = 3, case isolation alone can control a SARS outbreak only if isolation reduces transmission by at least a factor of four and the mean symptom-onset-to-isolation time is less than 3 days. Delays of a few days in contact tracing and case identification severely degrade the utility of quarantine and isolation, particularly in high-transmission settings. Still more detrimental are delays between the onset of an outbreak and the implementation of control measures; for given control scenarios, our model identifies windows of opportunity beyond which the efficacy of containment efforts is reduced greatly. By considering pathways of transmission in our system, we show that if hospital-based transmission is not halted, measures that reduce community-HCW contact are vital to preventing a widespread epidemic. The implications of our results for future emerging pathogens are discussed.",,"['Lloyd-Smith, James O', 'Galvani, Alison P', 'Getz, Wayne M']",,,,
,PMC,In brief,,PMC214064,,,,,,,,,
,PMC,"A Global Network for Early Warning and Response to Infectious Diseases and Bioterrorism: Applied Epidemiology and Training Programs, 2001",,PMC1448027,,,"In many ministries of health, applied epidemiology and training programs (AETPs) are responsible for detecting and responding to acute health events, including bioterrorism. In November 2001, we assessed the bioterrorism response capacity of 29 AETPs; 17 (59%) responded. Fifteen countries (88%) had bioterrorism response plans; in 6 (40%), AETPs took the lead in preparation and in 6 (40%) they assisted. Between September 11 and November 29, 2001, 12 AETPs (71%) responded to a total of 3024 bioterrorism-related phone calls. Six programs (35%) responded to suspected bioterrorism events. AETPs play an important role in bioterrorism surveillance and response. Support for this global network by various health agencies is beneficial for all developed and developing countries.",,"['Sandhu, Hardeep S.', 'Thomas, Christopher', 'Nsubuga, Peter', 'White, Mark E.']",,,,
,PMC,Eliminating Health Inequalities,,PMC1448019,,,,,"Ibrahim, Said A.",,,,
,PMC,From the library,,PMC1920782,,,,,,,,,
,PMC,Canadian surgery and the events of 2003,,PMC3211716,,,,,"Warnock, Garth L.",,,,
,PMC,The 2nd Meeting of the Canadian Animal Health Laboratorians Network,,PMC340303,,,,,,,,,
,PMC,"SseG, a virulence protein that targets Salmonella to the Golgi network",http://dx.doi.org/10.1093/emboj/cdg517,PMC204495,,,"Intracellular replication of the bacterial pathogen Salmonella enterica occurs in membrane-bound compartments called Salmonella-containing vacuoles (SCVs). Maturation of the SCV has been shown to occur by selective interactions with the endocytic pathway. We show here that after invasion of epithelial cells and migration to a perinuclear location, the majority of SCVs become surrounded by membranes of the Golgi network. This process is dependent on the Salmonella pathogenicity island 2 type III secretion system effector SseG. In infected cells, SseG was associated with the SCV and peripheral punctate structures. Only bacterial cells closely associated with the Golgi network were able to multiply; furthermore, mutation of sseG or disruption of the Golgi network inhibited intracellular bacterial growth. When expressed in epithelial cells, SseG co-localized extensively with markers of the trans-Golgi network. We identify a Golgi-targeting domain within SseG, and other regions of the protein that are required for localization of bacteria to the Golgi network. Therefore, replication of Salmonella in epithelial cells is dependent on simultaneous and selective interactions with both endocytic and secretory pathways.",,"['Salcedo, Suzana P.', 'Holden, David W.']",,,,
,PMC,Fierce creatures,http://dx.doi.org/10.1038/sj.embor.embor949,PMC1326407,,,"Zoonoses, diseases that jump from animals to humans, are a growing health problem around the world. Understanding their causes and their effects on humans have therefore become an important topic for global public health",,"Breithaupt, Holger",,,,
,PMC,Evaluation of Reverse Transcription-PCR Assays for Rapid Diagnosis of Severe Acute Respiratory Syndrome Associated with a Novel Coronavirus,http://dx.doi.org/10.1128/JCM.41.10.4521-4524.2003,PMC254368,,,"The reverse transcription (RT)-PCR protocols of two World Health Organization (WHO) severe acute respiratory syndrome (SARS) network laboratories (WHO SARS network laboratories at The University of Hong Kong [WHO-HKU] and at the Bernhard-Nocht Institute in Hamburg, Germany [WHO-Hamburg]) were evaluated for rapid diagnosis of a novel coronavirus (CoV) associated with SARS in Hong Kong. A total of 303 clinical specimens were collected from 163 patients suspected to have SARS. The end point of both WHO-HKU and WHO-Hamburg RT-PCR assays was determined to be 0.1 50% tissue culture infective dose. Using seroconversion to CoV as the “gold standard” for SARS CoV diagnosis, WHO-HKU and WHO-Hamburg RT-PCR assays exhibited diagnostic sensitivities of 61 and 68% (nasopharyngeal aspirate specimens), 65 and 72% (throat swab specimens), 50 and 54% (urine specimens), and 58 and 63% (stool specimens), respectively, with an overall specificity of 100%. For patients confirmed to have SARS CoV and from whom two or more respiratory specimens were collected, testing the second specimen increased the sensitivity from 64 and 71% to 75 and 79% for the WHO-HKU and WHO-Hamburg RT-PCR assays, respectively. Testing more than one respiratory specimen will maximize the sensitivity of PCR assays for SARS CoV.",,"['Yam, W. C.', 'Chan, K. H.', 'Poon, L. L. M.', 'Guan, Y.', 'Yuen, K. Y.', 'Seto, W. H.', 'Peiris, J. S. M.']",,,,
,PMC,Molecular Detection and Identification of Influenza Viruses by Oligonucleotide Microarray Hybridization,http://dx.doi.org/10.1128/JCM.41.10.4542-4550.2003,PMC254299,,,"Microarrays of virus-specific oligonucleotides may provide a method of screening samples for the presence or absence of a large variety of viruses simultaneously. Influenza viruses are ideal for evaluating such microarrays because of their genetic and host diversity, and the availability of an extensive sequence database. A collection of 476 influenza virus-specific oligonucleotides was spotted onto glass slides as probes. Viral RNAs were reverse transcribed and amplified by PCR, and the products were labeled with cyanine dyes. The presence of viruses and their identities were determined by hybridization. The fluorescence intensities of oligonucleotide spots were highly reproducible within each slide and satisfactorily proportional between experiments. However, the intensities of probe spots completely complementary to target sequences varied from background to saturation. The variations did not correlate with base composition, nucleotide sequence, or internal secondary structures. Therefore, thresholds for determining whether hybridization to a spot should be judged as positive were assigned individually. Considering only positive spots from probes predicted to be monospecific for influenza virus species, subtype, host source, or gene segment, this method made correct identifications at the species, hemagglutinin subtype, and gene segment levels. Monospecific neuraminidase (NA) subtype probes were insufficiently diverse to allow confident NA subtype assignment. Incorporating positive spots from polyspecific probes into the identification scheme gave similar results. Overall, the results demonstrate the potential of microarray-based oligonucleotide hybridization for multiple virus detection.",,"['Sengupta, Srikumar', 'Onodera, Kenji', 'Lai, Alexander', 'Melcher, Ulrich']",,,,
,PMC,Future outbreaks will be less dramatic,http://dx.doi.org/10.1136/jech.57.10.773,PMC1732312,,,,,"['Hsu, L', 'Paton, N']",,,,
,PMC,Identification and control are the priority,http://dx.doi.org/10.1136/jech.57.10.772,PMC1732309,,,,,"Rezza, G",,,,
,PMC,Virus pathogens suggest an autumn return,http://dx.doi.org/10.1136/jech.57.10.770-a,PMC1732306,,,,,"Abdullah, A",,,,
,PMC,Learn from influenza epidemiology,http://dx.doi.org/10.1136/jech.57.10.777,PMC1732301,,,,,"Regan, M",,,,
,PMC,Host and environment are key factors,http://dx.doi.org/10.1136/jech.57.10.770,PMC1732298,,,,,"Lee, A",,,,
,PMC,Out of the woods or in the eye of the storm?,http://dx.doi.org/10.1136/jech.57.10.776,PMC1732297,,,,,"Chotani, R",,,,
,PMC,Avoid complacency—prepare for the worst,http://dx.doi.org/10.1136/jech.57.10.775,PMC1732292,,,,,"Sung, J",,,,
,PMC,Monitoring the severe acute respiratory syndrome epidemic and assessing effectiveness of interventions in Hong Kong Special Administrative Region,http://dx.doi.org/10.1136/jech.57.10.766,PMC1732291,,,Objective: To estimate the infection curve of severe acute respiratory syndrome (SARS) using the back projection method and to assess the effectiveness of interventions. Design: Statistical method. Data: The daily reported number of SARS and interventions taken by Hong Kong Special Administrative Region (HKSAR) up to 24 June 2003 are used. Method: To use a back projection technique to construct the infection curve of SARS in Hong Kong. The estimated epidemic curve is studied to identify the major events and to assess the effectiveness of interventions over the course of the epidemic. Results: The SARS infection curve in Hong Kong is constructed for the period 1 March 2003 to 24 June 2003. Some interventions seem to be effective while others apparently have little or no effect. The infections among the medical and health workers are high. Conclusions: Quarantine of the close contacts of confirmed and suspected SARS cases seems to be the most effective intervention against spread of SARS in the community. Thorough disinfection of the infected area against environmental hazards is helpful. Infections within hospitals can be reduced by better isolation measures and protective equipments.,,"['Chau, P', 'Yip, P']",,,,
,PMC,Sporadic contact with unfamiliar source makes epidemic unlikely,http://dx.doi.org/10.1136/jech.57.10.772-a,PMC1732286,,,,,"Wong, T",,,,
,PMC,Vigorous controls minimise risk,http://dx.doi.org/10.1136/jech.57.10.774,PMC1732285,,,,,"Lee, S",,,,
,PMC,A simple approximate mathematical model to predict the number of severe acute respiratory syndrome cases and deaths,http://dx.doi.org/10.1136/jech.57.10.831,PMC1732283,,,"Background: Severe acute respiratory syndrome (SARS) is currently spreading in many countries. This paper proposes a simple approximate mathematical model for public health practitioners to predict the number of SARS cases and deaths. Methods: The model is based on four parameters: R(o) (basic reproductive number), F (case-fatality rate), i (incubation period), and d (duration of disease). The calculations can be done by hand or by using a computer spreadsheet. Results: The best parameters to fit Canadian data as of 6 April 2003 (before infection controls took effect) are R(o) = 1.5, F = 30%, i = 5 days, d = 14 days. On 6 April (day 40) there were 74 cases and 7 deaths. If this trend continues, SARS numbers in Canada are predicted to be as follows: 387 cases and 34 deaths by 26 April (day 60), 4432 cases and 394 deaths by 26 May (day 90), and 50 500 cases and 4489 deaths by 25 June (day 120). By comparison, the best parameters to fit Hong Kong data as of 10 April 2003 are R(o) = 2.0, F = 20%, i = 5 days, d = 14 days. Conclusions: Using the proposed mathematical model, it was estimated that about 1.5 to 2 new infectious cases were produced per infectious case every five days. Also, about 20% to 30% of the cases die within 14 days. The case-fatality may therefore be considerably higher than initially thought. The model indicates that SARS can spread very fast when there are no interventions.",,"['Choi, B', 'Pak, A']",,,,
,PMC,"Enhanced Virulence Mediated by the Murine Coronavirus, Mouse Hepatitis Virus Strain JHM, Is Associated with a Glycine at Residue 310 of the Spike Glycoprotein",http://dx.doi.org/10.1128/JVI.77.19.10260-10269.2003,PMC228498,,,"The coronavirus, mouse hepatitis virus strain JHM, causes acute and chronic neurological diseases in rodents. Here we demonstrate that two closely related virus variants, both of which cause acute encephalitis in susceptible strains of mice, cause markedly different diseases if mice are protected with a suboptimal amount of an anti-JHM neutralizing antibody. One strain, JHM.SD, caused acute encephalitis, while infection with JHM.IA resulted in no acute disease. Using recombinant virus technology, we found that the differences between the two viruses mapped to the spike (S) glycoprotein and that the two S proteins differed at four amino acids. By engineering viruses that differed by only one amino acid, we identified a serine-to-glycine change at position 310 of the S protein (S310G) that recapitulated the more neurovirulent phenotype. The increased neurovirulence mediated by the virus encoding glycine at position S310 was not associated with a different tropism within the central nervous system (CNS) but was associated with increased lateral spread in the CNS, leading to significantly higher brain viral titers. In vitro studies revealed that S310G was associated with decreased S1-S2 stability and with enhanced ability to mediate infection of cells lacking the primary receptor for JHM (“receptor-independent spread”). These enhanced fusogenic properties of viruses encoding a glycine at position 310 of the S protein may contribute to spread within the CNS, a tissue in which expression of conventional JHM receptors is low.",,"['Ontiveros, Evelena', 'Kim, Taeg S.', 'Gallagher, Thomas M.', 'Perlman, Stanley']",,,,
,PMC,"Characterization of the Expression, Intracellular Localization, and Replication Complex Association of the Putative Mouse Hepatitis Virus RNA-Dependent RNA Polymerase",http://dx.doi.org/10.1128/JVI.77.19.10515-10527.2003,PMC228489,,,"Mouse hepatitis virus (MHV) RNA synthesis is mediated by a viral RNA-dependent RNA polymerase (RdRp) on membrane-bound replication complexes in the host cell cytoplasm. However, it is not known how the putative MHV RdRp (Pol) is targeted to and retained on cellular membranes. In this report, we show that a 100-kDa protein was stably detected by an anti-Pol antiserum as a mature product throughout the virus life cycle. Gradient fractionation and biochemical extraction experiments demonstrated that Pol was not an integral membrane protein but was tightly associated with membranes and coimmunoprecipitated with the replicase proteins 3CLpro, p22, and p12. By immunofluorescence confocal microscopy, Pol colocalized with viral proteins at replication complexes, distinct from sites of virion assembly, over the entire course of infection. To determine if Pol associated with cellular membranes in the absence of other viral factors, the pol domain of gene 1 was cloned and expressed in cells as a fusion with green fluorescent protein, termed Gpol. In Gpol-expressing cells that were infected with MHV, but not in mock-infected cells, Gpol relocalized from a diffuse distribution in the cytoplasm to punctate foci that colocalized with markers for replication complexes. Expression of Gpol deletion mutants established that the conserved enzymatic domains of Pol were dispensable for replication complex association, but a 38-amino-acid domain in the RdRp unique region of Pol was required. This study demonstrates that viral or virus-induced factors are necessary for Pol to associate with membranes of replication complexes, and it identifies a defined region of Pol that may mediate its interactions with those factors.",,"['Brockway, Sarah M.', 'Clay, Corrie T.', 'Lu, Xiao Tao', 'Denison, Mark R.']",,,,
,PMC,Multiple Type A/B Heterogeneous Nuclear Ribonucleoproteins (hnRNPs) Can Replace hnRNP A1 in Mouse Hepatitis Virus RNA Synthesis,http://dx.doi.org/10.1128/JVI.77.19.10584-10593.2003,PMC228381,,,"Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 has previously been shown to bind mouse hepatitis virus (MHV) RNA at the 3′ end of both plus and minus strands and modulate MHV RNA synthesis. However, a mouse erythroleukemia cell line, CB3, does not express hnRNP A1 but still supports MHV replication, suggesting that alternative proteins can replace hnRNP A1 in cellular functions and viral infection. In this study, we set out to identify these proteins. UV cross-linking experiments revealed that several CB3 cellular proteins similar in size to hnRNP A1 interacted with the MHV RNA. These proteins were purified by RNA affinity column with biotinylated negative-strand MHV leader RNA and identified by mass spectrometry to be hnRNP A2/B1, hnRNP A/B, and hnRNP A3, all of which belong to the type A/B hnRNPs. All of these proteins contain amino acid sequences with strong similarity to the RNA-binding domains of hnRNP A1. Some of these hnRNPs have previously been shown to replace hnRNP A1 in regulating RNA splicing. These proteins displayed MHV RNA-binding affinity and specificity similar to those of hnRNP A1. hnRNP A2/B1, which is predominantly localized to the nucleus and shuttles between the nucleus and the cytoplasm, was shown to relocalize to the cytoplasm in MHV-infected CB3 cells. Furthermore, overexpression of hnRNP A/B in cells enhanced MHV RNA synthesis. Our findings demonstrate that the functions of hnRNP A1 in MHV RNA synthesis can be replaced by other closely related hnRNPs, further supporting the roles of cellular proteins in MHV RNA synthesis.",,"['Shi, Stephanie T.', 'Yu, Guann-Yi', 'Lai, Michael M. C.']",,,,
,PMC,Profile–profile comparisons by COMPASS predict intricate homologies between protein families,,PMC2366929,,,"Recently we proposed a novel method of alignment–alignment comparison, COMPASS (the tool for COmparison of Multiple Protein Alignments with Assessment of Statistical Significance). Here we present several examples of the relations between PFAM protein families that were detected by COMPASS and that lead to the predictions of presently unresolved protein structures. We discuss relatively straightforward COMPASS predictions that are new and interesting to us, and that would require a substantial time and effort to justify even for a skilled PSI-BLAST user. All of the presented COMPASS hits are independently confirmed by other methods, including the ab initio structure-prediction method ROSETTA. The tertiary structure predictions made by ROSETTA proved to be useful for improving sequence-derived alignments, because they are based on a reasonable folding of the polypeptide chain rather than on the information from sequence databases. The ability of COMPASS to predict new relations within the PFAM database indicates the high sensitivity of COMPASS searches and substantiates its potential value for the discovery of previously unknown similarities between protein families.",,"['Sadreyev, Ruslan I.', 'Baker, David', 'Grishin, Nick V.']",,,,
,PMC,Using research knowledge to improve health care,http://dx.doi.org/10.1136/qhc.12.5.322,PMC1743767,,,,,"Buchan, H",,,,
,PMC,A tragic death: a time to blame or a time to learn?,http://dx.doi.org/10.1136/qhc.12.5.321,PMC1743757,,,,,"['Runciman, W', 'Merry, A']",,,,
,PMC,SARS linked genetically to animals in China,,PMC202293,,,,,"Gandey, Allison",,,,
,PMC,SARS had immense impact on some MDs' practices,,PMC202292,,,,,"Mackay, Brad",,,,
,PMC,WHO issues global alert after grim report on HIV/AIDS,,PMC200831,,,,,"Fleck, Fiona",,,,
,PMC,Communicating risks: Means that patients too have to learn to live with uncertainty,,PMC200790,,,,,"Edwards, Adrian",,,,
,PMC,"News skews health priorities, study claims",,PMC196447,,,,,"Jackson, Trevor",,,,
,PMC,In brief,,PMC196386,,,,,,,,,
,PMC,SARS respiratory protection,,PMC191266,,,,,"Lange, John H.",,,,
,PMC,Asymptomatic animal traders prove positive for SARS virus,,PMC1140695,,,,,"Parry, Jane",,,,
,PMC,SARS: understanding the coronavirus: Apoptosis may explain lymphopenia of SARS,,PMC194123,,,,,"[""O'Donnell, Roddy"", 'Tasker, Robert C', 'Roe, Michael F E']",,,,
,PMC,SARS: understanding the coronavirus: Accuracy of WHO criteria was similar in a “non-SARS” hospital in Singapore,,PMC194122,,,,,"['Tambyah, Paul Ananth', 'Singh, Kamaljit S', 'Habib, Abdul G']",,,,
,PMC,Drug users in China tested for HIV without consent,,PMC194076,,,,,"Mayor, Susan",,,,
,PMC,In brief,,PMC194075,,,,,,,,,
,PMC,Molecular epidemiology of infectious diseases: a case for increased surveillance.,,PMC2572505,,,,,"Hasnain, Seyed E.",,,,
,PMC,Infection control for SARS in a tertiary neonatal centre,http://dx.doi.org/10.1136/fn.88.5.F405,PMC1721604,,,"The Severe Acute Respiratory Syndrome (SARS) is a newly discovered infectious disease caused by a novel coronavirus, which can readily spread in the healthcare setting. A recent community outbreak in Hong Kong infected a significant number of pregnant women who subsequently required emergency caesarean section for deteriorating maternal condition and respiratory failure. As no neonatal clinician has any experience in looking after these high risk infants, stringent infection control measures for prevention of cross infection between patients and staff are important to safeguard the wellbeing of the work force and to avoid nosocomial spread of SARS within the neonatal unit. This article describes the infection control and patient triage policy of the neonatal unit at the Prince of Wales Hospital, Hong Kong. We hope this information is useful in helping other units to formulate their own infection control plans according to their own unit configuration and clinical needs.",,"['Ng, P', 'So, K', 'Leung, T', 'Cheng, F', 'Lyon, D', 'Wong, W', 'Cheung, K', 'Fung, K', 'Lee, C', 'Li, A', 'Hon, K', 'Li, C', 'Fok, T']",,,,
,PMC,Editorial freedom in Focus.,,PMC1314702,,,,,"Church, David",,,,
,PMC,Primary care during the SARS outbreak.,,PMC1314701,,,,,"['Lee, Albert', 'Wong, William']",,,,
,PMC,Appraisal of family doctors.,,PMC1314700,,,,,"['McKinstry, Brian', 'Peacock, Heather']",,,,
,PMC,The blind alley of decision analysis.,,PMC1314699,,,,,"Kernick, D P",,,,
,PMC,The ILS course: an answer for MRCGP basic life support?,,PMC1314698,,,,,"['Moody-Jones, W D', 'Stevens, H']",,,,
,PMC,From the Library,,PMC1771855,,,,,,,,,
,PMC,Retrospective analysis of etiologic agents associated with respiratory diseases in pigs,,PMC340270,,,"Twenty-eight hundred and seventy-two cases of respiratory disease in pigs were analyzed for their etiologic agents. Two or more pathogens were detected from 88.2% of the cases, indicating that porcine reproductive and respiratory syndrome virus (PRRSV) or swine influenza virus (SIV) combined with other bacterial agents was a common cause for porcine respiratory diseases in the mid-western USA.",,"['Choi, Young Ki', 'Goyal, Sagar M.', 'Joo, Han Soo']",,,,
,PMC,Singapore's experience of SARS,http://dx.doi.org/10.7861/clinmedicine.3-5-448,PMC4953642,,,"The coronavirus that causes severe acute respiratory syndrome (SARS) is transmitted mainly via respiratory droplets. Typical presenting symptoms are akin to those of ordinary pneumonia. Young patients start with fever, chills, malaise, headache, or myalgia; cough and dyspnoea follow. Older persons and those taking corticosteroids may have neither fever nor respiratory symptoms. Exceptional suspicion is needed to identify SARS early in the illness. During an outbreak, even patients with low suspicion of SARS should be promptly isolated, and all contacts quarantined. Health workers need training in the use of appropriate barriers against droplets and other body fluids. Any fever cluster in patients or carers requires immediate action: discharges, visits, and transfers between wards and hospitals should be stopped. Halting hospital admissions and ten-day quarantine of suspected cases create wide buffer zones. To counter a possible resurgence of SARS, a system of prepared isolation and quarantine facilities is important.",,"['Oh, Vernon MS', 'Lim, TK']",,,,
,PMC,"Sex, SARS, and the Holy Grail",http://dx.doi.org/10.1136/emj.20.5.400,PMC1726213,,,,,"Schull, M",,,,
,PMC,"Health care policy makers, we have a problem",http://dx.doi.org/10.1136/emj.20.5.399,PMC1726186,,,,,"['Wardrope, J', 'Driscoll, P']",,,,
,PMC,Primary Survey,http://dx.doi.org/10.1136/emj.20.5.397,PMC1726178,,,,,"['Driscoll, P.', 'Wardope, J.']",,,,
,PMC,JournalScan,http://dx.doi.org/10.1136/emj.20.5.471,PMC1726176,,,,,"['Wyatt, J', 'Jones, L']",,,,
,PMC,Technical Description of RODS: A Real-time Public Health Surveillance System,http://dx.doi.org/10.1197/jamia.M1345,PMC212776,,,"This report describes the design and implementation of the Real-time Outbreak and Disease Surveillance (RODS) system, a computer-based public health surveillance system for early detection of disease outbreaks. Hospitals send RODS data from clinical encounters over virtual private networks and leased lines using the Health Level 7 (HL7) message protocol. The data are sent in real time. RODS automatically classifies the registration chief complaint from the visit into one of seven syndrome categories using Bayesian classifiers. It stores the data in a relational database, aggregates the data for analysis using data warehousing techniques, applies univariate and multivariate statistical detection algorithms to the data, and alerts users of when the algorithms identify anomalous patterns in the syndrome counts. RODS also has a Web-based user interface that supports temporal and spatial analyses. RODS processes sales of over-the-counter health care products in a similar manner but receives such data in batch mode on a daily basis. RODS was used during the 2002 Winter Olympics and currently operates in two states—Pennsylvania and Utah. It has been and continues to be a resource for implementing, evaluating, and applying new methods of public health surveillance.",,"['Tsui, Fu-Chiang', 'Espino, Jeremy U.', 'Dato, Virginia M.', 'Gesteland, Per H.', 'Hutman, Judith', 'Wagner, Michael M.']",,,,
,PMC,GeneScan Reverse Transcription-PCR Assay for Detection of Six Common Respiratory Viruses in Young Children Hospitalized with Acute Respiratory Illness,http://dx.doi.org/10.1128/JCM.41.9.4298-4303.2003,PMC193844,,,"A reverse transcription-PCR (RT-PCR) assay based on automated fluorescent capillary electrophoresis and GeneScan software analysis was developed to detect six common respiratory viruses in clinical specimens from young children. Assays for human respiratory syncytial virus (HRSV); human parainfluenza viruses 1, 2, and 3 (HPIV1, -2, and -3, respectively); and influenza A and B viruses were incorporated into a single standard assay format. The optimized assay panel was used to test 470 respiratory specimens obtained from 462 children hospitalized with acute respiratory illness that had been previously tested by viral culture (405 specimens) or direct immunofluorescence staining (DIF) (65 specimens). Of 93 specimens positive for respiratory viruses by culture or DIF, 86 (92%) were positive by RT-PCR, including 66 HRSV, 2 HPIV2, 5 HPIV3, 3 influenza A virus, and 10 influenza B virus specimens. An additional 119 respiratory viruses were identified by RT-PCR in 116 patients for whom results were negative by viral isolation or DIF. We conclude that the GeneScan RT-PCR panel can markedly improve detection of acute respiratory virus infections in young children.",,"['Erdman, Dean D.', 'Weinberg, Geoffrey A.', 'Edwards, Kathryn M.', 'Walker, Frances J.', 'Anderson, Barbara C.', 'Winter, Jörn', 'González, Monica', 'Anderson, Larry J.']",,,,
,PMC,Severe acute respiratory syndrome and Toronto,http://dx.doi.org/10.1136/jech.57.9.642,PMC1732595,,,,,"Regan, M",,,,
,PMC,Severe acute respiratory syndrome: a challenge for public health practice in Hong Kong,http://dx.doi.org/10.1136/jech.57.9.655,PMC1732589,,,"Severe acute respiratory syndrome (SARS) is now a global challenge affecting more than 8000 patients in different continents. The dictum of public health practice especially for infectious disease is ""prevention better than cure"". It is especially true for SARS as the treatment strategies remain diverse and experimental. Maintaining a healthy and hygienic environment can be one of the effective public health measures to combat infectious disease. The major challenge is that some of the most important public health measures are to be taken outside the health sector. The community also needs to be strengthened and equipped with the health skills to promote better health and hygiene. There is also the need to create a supportive environment conducive to health for long term sustainability. The WHO approach of promoting health through setting approach would be one possible solution to face the challenge. This paper will describe some of the public health initiatives in Hong Kong through ""setting approach"" and ""community development model"" in helping the society fight against SARS. With the emergence of SARS, this might be the time to globalise public health medicine as an important component of medical practice.",,"['Lee, A', 'Abdullah, A']",,,,
,PMC,The SARS epidemic in Hong Kong,http://dx.doi.org/10.1136/jech.57.9.652,PMC1732583,,,,,"Lee, S",,,,
,PMC,"Science, policy, politics, a complex and unequal world and the emerging of a new infectious disease",http://dx.doi.org/10.1136/jech.57.9.644,PMC1732567,,,,,"Barreto, M",,,,
,PMC,Severe acute respiratory syndrome,http://dx.doi.org/10.1136/jech.57.9.643,PMC1732565,,,,,"Rezza, G",,,,
,PMC,Functional Analysis of Mosquito-Borne Flavivirus Conserved Sequence Elements within 3′ Untranslated Region of West Nile Virus by Use of a Reporting Replicon That Differentiates between Viral Translation and RNA Replication,http://dx.doi.org/10.1128/JVI.77.18.10004-10014.2003,PMC224605,,,"We have developed a reporting replicon of West Nile virus (WNV) that could be used to quantitatively distinguish viral translation and RNA replication. A Renilla luciferase (Rluc) gene was fused in-frame with the open reading frame of a subgenomic replicon in the position where the viral structural region was deleted, resulting in RlucRep. Transfection of BHK cells with RlucRep RNA yielded two distinctive Rluc signal peaks, one between 2 and 10 h and the other after 26 h posttransfection. By contrast, only the 2- to 10-h Rluc signal peak was observed in cells transfected with a mutant replicon containing an inactivated viral polymerase NS5 (RlucRep-NS5mt). Immunofluorescence and real-time reverse transcriptase PCR assays showed that the levels of viral protein expression and RNA replication increased in cells transfected with the RlucRep but not in those transfected with the RlucRep-NS5mt. These results suggest that the Rluc signal that occurred at 2 to 10 h posttransfection reflects viral translation of the input replicon, while the Rluc activity after 26 h posttransfection represents RNA replication. Using this system, we showed that mutations of conserved sequence (CS) elements within the 3′ untranslated region of the mosquito-borne flaviviruses did not significantly affect WNV translation but severely diminished or completely abolished RNA replication. Mutations of CS1 that blocked the potential base pairing with a conserved sequence in the 5′ region of the capsid gene (5′CS) abolished RNA replication. Restoration of the 5′CS-CS1 interaction rescued viral replication. Replicons containing individual deletions of CS2, repeated CS2 (RCS2), CS3, or RCS3 were viable, but their RNA replication was dramatically compromised. These results demonstrate that genome cyclization through the 5′CS-CS1 interaction is essential for WNV RNA replication, whereas CS2, RCS2, CS3, and RCS3 facilitate, but are dispensable for, WNV replication.",,"['Lo, Michael K.', 'Tilgner, Mark', 'Bernard, Kristen A.', 'Shi, Pei-Yong']",,,,
,PMC,Multigene RNA Vector Based on Coronavirus Transcription,http://dx.doi.org/10.1128/JVI.77.18.9790-9798.2003,PMC224574,,,"Coronavirus genomes are the largest known autonomously replicating RNAs with a size of ca. 30 kb. They are of positive polarity and are translated to produce the viral proteins needed for the assembly of an active replicase-transcriptase complex. In addition to replicating the genomic RNA, a key feature of this complex is a unique transcription process that results in the synthesis of a nested set of six to eight subgenomic mRNAs. These subgenomic mRNAs are produced in constant but nonequimolar amounts and, in general, each is translated to produce a single protein. To take advantage of these features, we have developed a multigene expression vector based on human coronavirus 229E. We have constructed a prototype RNA vector containing the 5′ and 3′ ends of the human coronavirus genome, the entire human coronavirus replicase gene, and three reporter genes (i.e., the chloramphenicol acetyltransferase [CAT] gene, the firefly luciferase [LUC] gene, and the green fluorescent protein [GFP] gene). Each reporter gene is located downstream of a human coronavirus transcription-associated sequence, which is required for the synthesis of individual subgenomic mRNAs. The transfection of vector RNA and human coronavirus nucleocapsid protein mRNA into BHK-21 cells resulted in the expression of the CAT, LUC, and GFP reporter proteins. Sequence analysis confirmed the synthesis of coronavirus-specific mRNAs encoding CAT, LUC, and GFP. In addition, we have shown that human coronavirus-based vector RNA can be packaged into virus-like particles that, in turn, can be used to transduce immature and mature human dendritic cells. In summary, we describe a new class of eukaryotic, multigene expression vectors that are based on the human coronavirus 229E and have the ability to transduce human dendritic cells.",,"['Thiel, Volker', 'Karl, Nadja', 'Schelle, Barbara', 'Disterer, Petra', 'Klagge, Ingo', 'Siddell, Stuart G.']",,,,
,PMC,Phylogenetic and Evolutionary Relationships among Torovirus Field Variants: Evidence for Multiple Intertypic Recombination Events,http://dx.doi.org/10.1128/JVI.77.17.9567-9577.2003,PMC187415,,,"Toroviruses (family Coronaviridae, order Nidovirales) are enveloped, positive-stranded RNA viruses that have been implicated in enteric disease in cattle and possibly in humans. Despite their potential veterinary and clinical relevance, little is known about torovirus epidemiology and molecular genetics. Here, we present the first study into the diversity among toroviruses currently present in European swine and cattle herds. Comparative sequence analysis was performed focusing on the genes for the structural proteins S, M, HE, and N, with fecal specimens serving as sources of viral RNA. Sequence data published for animal and human torovirus variants were included. Four genotypes, displaying 30 to 40% divergence, were readily distinguished, exemplified by bovine torovirus (BToV) Breda, porcine torovirus (PToV) Markelo, equine torovirus Berne, and the putative human torovirus. The ungulate toroviruses apparently display host species preference. In phylogenetic analyses, all PToV variants clustered, while the recent European BToVs mostly resembled the New World BToV variant Breda, identified 19 years ago. However, we found ample evidence for recurring intertypic recombination. All newly characterized BToV variants seem to have arisen from a genetic exchange, during which the 3′ end of the HE gene, the N gene, and the 3′ nontranslated region of a Breda virus-like parent had been swapped for those of PToV. Moreover, some PToV and BToV variants carried chimeric HE genes, which apparently resulted from recombination events involving hitherto unknown toroviruses. From these observations, the existence of two additional torovirus genotypes can be inferred. Toroviruses may be even more promiscuous than their closest relatives, the coronaviruses and arteriviruses.",,"['Smits, S. L.', 'Lavazza, A.', 'Matiz, K.', 'Horzinek, M. C.', 'Koopmans, M. P.', 'de Groot, R. J.']",,,,
,PMC,"Antiviral Activity of Limitin against Encephalomyocarditis Virus, Herpes Simplex Virus, and Mouse Hepatitis Virus: Diverse Requirements by Limitin and Alpha Interferon for Interferon Regulatory Factor 1",http://dx.doi.org/10.1128/JVI.77.17.9622-9631.2003,PMC187381,,,"Limitin has sequence homology with alpha interferon (IFN-α) and IFN-β and utilizes the IFN-α/β receptor. However, it has no influence on the proliferation of normal myeloid and erythroid progenitors. In this study, we show that limitin has antiviral activity in vitro as well as in vivo. Limitin inhibited not only cytopathic effects in encephalomyocarditis virus- or herpes simplex virus (HSV) type 1-infected L929 cells, but also plaque formation in mouse hepatitis virus (MHV) type 2-infected DBT cells. In addition, administration of limitin to mice suppressed MHV-induced hepatitis and HSV-induced death. The antiviral activity may be mediated in part by 2′,5′-oligoadenylate synthetase, RNA-dependent protein kinase, and Mx protein, which inhibit viral replication or degrade viral components, because limitin induced their mRNA expression and enzyme activity. While limitin has antiviral activity as strong as that of IFN-α in vitro (the concentration that provided 50% inhibition of cytopathic effect is ∼30 pg/ml), IFN regulatory factor 1 (IRF-1) dependencies for induction of an antiviral state were different for limitin and IFN-α. In IRF-1-deficient fibroblasts, a higher concentration of limitin than of IFN-α was required for the induction of antiviral activity and the transcription of proteins from IFN-stimulated response element. The unique signals and the fewer properties of myelosuppression suggest that a human homolog of limitin may be used as a new antiviral drug.",,"['Kawamoto, Shin-Ichiro', 'Oritani, Kenji', 'Asada, Hideo', 'Takahashi, Isao', 'Ishikawa, Jun', 'Yoshida, Hitoshi', 'Yamada, Masahide', 'Ishida, Naoko', 'Ujiie, Hidetoshi', 'Masaie, Hiroaki', 'Tomiyama, Yoshiaki', 'Matsuzawa, Yuji']",,,,
,PMC,WHO relaunches polio campaign,,PMC188376,,,,,"Fleck, Fiona",,,,
,PMC,WHO issues guidelines to manage any future SARS outbreak,,PMC188486,,,,,"Parry, Jane",,,,
,PMC,Should paramedics intubate patients with SARS-like symptoms?,,PMC180653,,,,,"['Verbeek, P. Richard', 'Schwartz, Brian', 'Burgess, Robert J.']",,,,
,PMC,"Investigation of a nosocomial outbreak of severe acute respiratory syndrome (SARS) in Toronto, Canada",,PMC180651,,,"BACKGROUND: Severe acute respiratory syndrome (SARS) was introduced into Canada by a visitor to Hong Kong who returned to Toronto on Feb. 23, 2003. Transmission to a family member who was later admitted to a community hospital in Toronto led to a large nosocomial outbreak. In this report we summarize the preliminary results of the epidemiological investigation into the transmission of SARS between 128 cases associated with this hospital outbreak. METHODS: We collected epidemiologic data on 128 probable and suspect cases of SARS associated with the hospital outbreak, including those who became infected in hospital and the next generation of illness arising among their contacts. Incubation periods were calculated based on cases with a single known exposure. Transmission chains from the index family to hospital contacts and within the hospital were mapped. Attack rates were calculated for nurses in 3 hospital wards where transmission occurred. RESULTS: The cases ranged in age from 21 months to 86 years; 60.2% were female. Seventeen deaths were reported (case-fatality rate 13.3%). Of the identified cases, 36.7% were hospital staff. Other cases were household or social contacts of SARS cases (29.6%), hospital patients (14.1%), visitors (14.1%) or other health care workers (5.5%). Of the 128 cases, 120 (93.8%) had documented contact with a SARS case or with a ward where there was a known SARS case. The remaining 8 cases without documented exposure are believed to have had exposure to an unidentified case and remain under investigation. The attack rates among nurses who worked in the emergency department, intensive care unit and coronary care unit ranged from 10.3% to 60.0%. Based on 42 of the 128 cases with a single known contact with a SARS case, the mean incubation period was 5 days (range 2 to 10 days). INTERPRETATION: Evidence to date suggests that SARS is a severe respiratory illness spread mainly by respiratory droplets. There has been no evidence of further transmission within the hospital after the elapse of 2 full incubation periods (20 days).",,"['Varia, Monali', 'Wilson, Samantha', 'Sarwal, Shelly', 'McGeer, Allison', 'Gournis, Effie', 'Galanis, Eleni', 'Henry, Bonnie', None]",,,,
,PMC,SARS case-fatality rates,,PMC180638,,,,,"['Fung, Wing K.', 'Yu, Philip L.H.']",,,,
,PMC,Lessons from Taiwan,,PMC180637,,,,,"['Chien, Li-chien', 'Yeh, Wen-Bin', 'Chang, Hong-Tai']",,,,
,PMC,Highlights of this issue,,PMC180636,,,,,,,,,
,PMC,"Second Opinion: Doctors, Diseases and Decisions in Modern Medicine",,PMC1126826,,,,,"Derbyshire, Stuart W G",,,,
,PMC,US army investigates unrelated pneumonia cases in troops in Iraq,,PMC1126784,,,,,"Gottlieb, Scott",,,,
,PMC,Current status of severe acute respiratory syndrome in China,http://dx.doi.org/10.3748/wjg.v9.i8.1635,PMC4611517,,,"Severe acute respiratory syndrome (SARS), also called infectious atypical pneumonia, is an emerging infectious disease caused by a novel variant of coronavirus (SARS-associated coronavirus, SARS-CoV). It is mainly characterized by pulmonary infection with a high infectivity and fatality. SARS is swept across almost all the continents of the globe, and has currently involved 33 countries and regions, including the mainland China, Hong Kong, Taiwan, North America and Europe. On June 30, 2003, an acumulative total reached 8450 cases with 810 deaths. SARS epidemic was very rampant in March, April and May 2003 in the mainland of China and Hong Kong. Chinese scientists and healthcare workers cooperated closely with other scientists from all over the world to fight the disease. On April 16, 2003, World Health Organization (WHO) formally declared that SARS-CoV was an etiological agent of SARS. Currently, there is no specific and effective therapy and prevention method for SARS. The main treatments include corticosteroid therapy, anti-viral agents, anti-infection, mechanical ventilation and isolation. This disease can be prevented and controlled, and it is also curable. Under the endeavor of the Chinese Government, medical staffs and other related professionals, SARS has been under control in China, and Chinese scientists have also made a great contribution to SARS research. Other studies in developing new detection assays and therapies, and discovering new drugs and vaccines are in progress. In this paper, we briefly review the current status of SARS in China.",,"['Nie, Qing-He', 'Luo, Xin-Dong', 'Zhang, Jian-Zhong', 'Su, Qin']",,,,
,PMC,New public health agency sets out its stall,,PMC1142512,,,,,"Pincock, Stephen",,,,
,PMC,Hong Kong under WHO spotlight after flu outbreak,,PMC1126722,,,,,"Parry, Jane",,,,
,PMC,EU health minister renews calls for specialist disease control centre,,PMC1150906,,,,,"Watson, Rory",,,,
,PMC,Childhood SARS in Singapore,http://dx.doi.org/10.1136/adc.88.8.742,PMC1719611,,,,,"['Van Bever, H', 'Hia, C', 'Swee, C']",,,,
,PMC,Food allergy in childhood,http://dx.doi.org/10.1136/adc.88.8.742-a,PMC1719583,,,,,"['Colver, A', 'Macdougall, C', 'Cant, A']",,,,
,PMC,SARS wars: family physicians undeployed soldiers.,,PMC2214280,,,,,"Leong, Renata M. W.",,,,
,PMC,Lack of interest in family medicine also in the United States.,,PMC2214276,,,,,"Grief, Samuel N.",,,,
,PMC,Where is the primary care viewpoint?,,PMC2214267,,,,,"['Murphy, David', 'Marshall, Lynn']",,,,
,PMC,Prokaryotic-style frameshifting in a plant translation system: conservation of an unusual single-tRNA slippage event,http://dx.doi.org/10.1093/emboj/cdg365,PMC169038,,,"Ribosomal frameshifting signals are found in mobile genetic elements, viruses and cellular genes of prokaryotes and eukaryotes. Typically they comprise a slippery sequence, X XXY YYZ, where the frameshift occurs, and a stimulatory mRNA element. Here we studied the influence of host translational environment and the identity of slippery sequence-decoding tRNAs on the frameshift mechanism. By expressing candidate signals in Escherichia coli, and in wheatgerm extracts depleted of endogenous tRNAs and supplemented with prokaryotic or eukaryotic tRNA populations, we show that when decoding AAG in the ribosomal A-site, E.coli tRNA(Lys) promotes a highly unusual single-tRNA slippage event in both prokaryotic and eukaryotic ribosomes. This event does not appear to require slippage of the adjacent P-site tRNA, although its identity is influential. Conversely, asparaginyl-tRNA promoted a dual slippage event in either system. Thus, the tRNAs themselves are the main determinants in the selection of single- or dual-tRNA slippage mechanisms. We also show for the first time that prokaryotic tRNA(Asn) is not inherently ‘unslippery’ and induces efficient frameshifting when in the context of a eukaryotic translation system.",,"['Napthine, Sawsan', 'Vidakovic, Marijana', 'Girnary, Roseanne', 'Namy, Olivier', 'Brierley, Ian']",,,,
,PMC,A global player for public health,http://dx.doi.org/10.1038/sj.embor.embor915,PMC1326351,,,"An interview with Tikki Pang, Director of Research Policy and Cooperation at the World Health Organization",,,,,,
,PMC,"Construction, Characterization, and Immunogenicity of an Attenuated Salmonella enterica Serovar Typhimurium pgtE Vaccine Expressing Fimbriae with Integrated Viral Epitopes from the spiC Promoter",http://dx.doi.org/10.1128/IAI.71.8.4664-4673.2003,PMC165986,,,"Transmissible gastroenteritis virus (TGEV) is a porcine coronavirus that causes diarrhea, leading to near 100% mortality in neonatal piglets with corresponding devastating economic consequences. For the protection of neonatal and older animals, oral live vaccines present the attractive property of inducing desired mucosal immune responses, including colostral antibodies in sows—an effective means to passively protect suckling piglets. Newly attenuated Salmonella vaccine constructs expressing TGEV S protein epitopes were studied and evaluated for improved humoral immune response to TGEV. The macrophage-inducible Salmonella ssaH and spiC/ssaB promoters were compared for their ability to express the TGEV C and A epitopes in the context of the heterologous 987P fimbriae on Salmonella vaccines. Compared to the ssaH promoter, the Salmonella cya crp vector elicited significantly higher levels of mucosal and systemic antibodies in orally immunized mice when the chimeric fimbriae were expressed from the spiC promoter. The Salmonella spiC promoter construct induced the highest level of chimeric fimbriae after being taken up by the J774A.1 macrophagelike cells. The Salmonella cya crp vaccine vector was shown to incorporate into 987P partially degraded chimeric subunits lacking the TGEV epitopes. In contrast, its isogenic pgtE mutant produced fimbriae consisting exclusively of intact chimeric subunits. Mice immunized orally with the Salmonella pgtE vaccine expressing chimeric fimbriae from the spiC promoter elicited significantly higher systemic and mucosal antibody titers against the TGEV epitopes compared to the parental vaccine. This study indicates that the Salmonella cya crp pgtE vector and the spiC promoter can be used successfully to improve immune responses toward heterologous antigens.",,"['Chen, Huaiqing', 'Schifferli, Dieter M.']",,,,
,PMC,Role of the Microbiology Laboratory in Diagnosis and Management of Pharyngitis,http://dx.doi.org/10.1128/JCM.41.8.3467-3472.2003,PMC179871,,,,,"Bourbeau, Paul P.",,,,
,PMC,The SARS epidemic in Hong Kong: what lessons have we learned?,,PMC539564,,,,,"Hung, Lee Shiu",,,,
,PMC,Epidemic infections and their relevance to the Gulf and other Arabian Peninsula countries,,PMC3174724,,,,,"Scrimgeour, Euan M.",,,,
,PMC,Recombinant Avian Infectious Bronchitis Virus Expressing a Heterologous Spike Gene Demonstrates that the Spike Protein Is a Determinant of Cell Tropism,http://dx.doi.org/10.1128/JVI.77.16.9084-9089.2003,PMC167237,,,"A recombinant infectious bronchitis virus (IBV), BeauR-M41(S), was generated using our reverse genetics system (R. Casais, V. Thiel, S. G. Siddell, D. Cavanagh, and P. Britton, J. Virol. 75:12359-12369, 2001), in which the ectodomain region of the spike gene from IBV M41-CK replaced the corresponding region of the IBV Beaudette genome. BeauR-M41(S) acquired the same cell tropism phenotype as IBV M41-CK in four different cell types, demonstrating that the IBV spike glycoprotein is a determinant of cell tropism.",,"['Casais, Rosa', 'Dove, Brian', 'Cavanagh, David', 'Britton, Paul']",,,,
,PMC,Residues in the Apical Domain of the Feline and Canine Transferrin Receptors Control Host-Specific Binding and Cell Infection of Canine and Feline Parvoviruses,http://dx.doi.org/10.1128/JVI.77.16.8915-8923.2003,PMC167234,,,"Canine parvovirus (CPV) and feline panleukopenia virus (FPV) capsids bind to the transferrin receptors (TfRs) of their hosts and use these receptors to infect cells. The binding is partially host specific, as FPV binds only to the feline TfR, while CPV binds to both the canine and feline TfRs. The host-specific binding is controlled by a combination of residues within a raised region of the capsid. To define the TfR structures that interact with the virus, we altered the apical domain of the feline or canine TfR or prepared chimeras of these receptors and tested the altered receptors for binding to FPV or CPV capsids. Most changes in the apical domain of the feline TfR did not affect binding, but replacing Leu221 with Ser or Asp prevented receptor binding to either FPV or CPV capsids, while replacing Leu221 with Lys resulted in a receptor that bound only to CPV but not to FPV. Analysis of recombinants of the feline and canine TfRs showed that sequences controlling CPV-specific binding were within the apical domain and that more than one difference between these receptors determined the CPV-specific binding of the canine TfR. Single changes within the canine TfR which removed a single amino acid insertion or which eliminated a glycosylation site gave that receptor the expanded ability to bind to FPV and CPV. In some cases, binding of capsids to mutant receptors did not result in infection, suggesting a structural role for the receptor in cell infection by the viruses.",,"['Palermo, Laura M.', 'Hueffer, Karsten', 'Parrish, Colin R.']",,,,
,PMC,A Hepadnavirus Regulatory Element Enhances Expression of a Type 2 Bovine Viral Diarrhea Virus E2 Protein from a Bovine Herpesvirus 1 Vector,http://dx.doi.org/10.1128/JVI.77.16.8775-8782.2003,PMC167231,,,"Recently, the possibility of using virus vectors to immunize cattle against selected bovine viral diarrhea virus (BVDV) genes has gained widespread interest. However, when we attempted to express the E2 protein from type 2 (890 strain) BVDV in a bovine herpesvirus 1 (BHV1) vector, we observed that expression was poor. This often happens when genes from a cytoplasmic virus are expressed in the cell nucleus. To counter this effect, we attempted to enhance expression by a strategy employed by viruses. RNAs of retroviruses and hepadnaviruses contain cis-acting elements that facilitate expression of RNAs that otherwise are degraded or retained within the nucleus. In Mason-Pfizer monkey virus, the required RNA sequence element is known as a constitutive transport element (CTE). A related element from woodchuck hepatitis virus is known as the woodchuck posttranscriptional regulatory element (WPRE). We tested the ability of the CTE, the WPRE, and introns to enhance expression of E2. All three elements stimulated expression of E2 from plasmids. The combination of the WPRE and an intron yielded the highest level of E2 expression in plasmids. However, when E2 was expressed from a BHV1 vector, the presence of an intron was inhibitory. In contrast, the WPRE was very efficient at stimulating E2 expression from a BHV1 vector. This result represents the first expression of a type 2 BVDV E2 protein from a mammalian virus vector and raises the possibility that the WPRE may provide a general method of enhancing foreign gene expression from BHV1 and other herpesvirus vectors.",,"['Wang, Lingshu', 'Menon, Sreekumar', 'Bolin, Steven R.', 'Bello, Leonard J.']",,,,
,PMC,Expression of Immunogenic S1 Glycoprotein of Infectious Bronchitis Virus in Transgenic Potatoes,http://dx.doi.org/10.1128/JVI.77.16.9090-9093.2003,PMC167223,,,"The expression of infectious bronchitis virus (IBV) S1 glycoprotein in potatoes and its immunogenicity in mice and chickens were investigated. Potato plants were genetically transformed with a cDNA construct encoding the IBV S1 glycoprotein with the Agrobacterium system. Genomic DNA and mRNA analyses of the transformed plantlets confirmed the integration of the foreign cDNA into the potato genome, as well as its transcription. Mice and chickens vaccinated with the expressed IBV S1 glycoprotein produced antibodies that neutralized IBV infectivity. After three immunizations, vaccinated chickens were completely protected from virulent IBV infection. These results demonstrate that transgenic potatoes expressing IBV S1 glycoprotein can be used as a source of recombinant antigen for vaccine production.",,"['Zhou, Ji-Yong', 'Wu, Jian-Xiang', 'Cheng, Li-Qin', 'Zheng, Xiao-Juan', 'Gong, Hui', 'Shang, Shao-Bin', 'Zhou, En-Min']",,,,
,PMC,The Coronavirus Spike Protein Is a Class I Virus Fusion Protein: Structural and Functional Characterization of the Fusion Core Complex,http://dx.doi.org/10.1128/JVI.77.16.8801-8811.2003,PMC167208,,,"Coronavirus entry is mediated by the viral spike (S) glycoprotein. The 180-kDa oligomeric S protein of the murine coronavirus mouse hepatitis virus strain A59 is posttranslationally cleaved into an S1 receptor binding unit and an S2 membrane fusion unit. The latter is thought to contain an internal fusion peptide and has two 4,3 hydrophobic (heptad) repeat regions designated HR1 and HR2. HR2 is located close to the membrane anchor, and HR1 is some 170 amino acids (aa) upstream of it. Heptad repeat (HR) regions are found in fusion proteins of many different viruses and form an important characteristic of class I viral fusion proteins. We investigated the role of these regions in coronavirus membrane fusion. Peptides HR1 (96 aa) and HR2 (39 aa), corresponding to the HR1 and HR2 regions, were produced in Escherichia coli. When mixed together, the two peptides were found to assemble into an extremely stable oligomeric complex. Both on their own and within the complex, the peptides were highly alpha helical. Electron microscopic analysis of the complex revealed a rod-like structure ∼14.5 nm in length. Limited proteolysis in combination with mass spectrometry indicated that HR1 and HR2 occur in the complex in an antiparallel fashion. In the native protein, such a conformation would bring the proposed fusion peptide, located in the N-terminal domain of HR1, and the transmembrane anchor into close proximity. Using biological assays, the HR2 peptide was shown to be a potent inhibitor of virus entry into the cell, as well as of cell-cell fusion. Both biochemical and functional data show that the coronavirus spike protein is a class I viral fusion protein.",,"['Bosch, Berend Jan', 'van der Zee, Ruurd', 'de Haan, Cornelis A. M.', 'Rottier, Peter J. M.']",,,,
,PMC,Host Factors in Positive-Strand RNA Virus Genome Replication,http://dx.doi.org/10.1128/JVI.77.15.8181-8186.2003,PMC165243,,,,,"['Ahlquist, Paul', 'Noueiry, Amine O.', 'Lee, Wai-Ming', 'Kushner, David B.', 'Dye, Billy T.']",,,,
,PMC,SARS and occupational health in the air,http://dx.doi.org/10.1136/oem.60.8.539,PMC1740596,,,,,"['Lim, M', 'Koh, D']",,,,
,PMC,Decreased peptidyltransferase activity correlates with increased programmed −1 ribosomal frameshifting and viral maintenance defects in the yeast Saccharomyces cerevisiae,http://dx.doi.org/10.1261/rna.2165803,PMC1240118,,,"Increased efficiencies of programmed −1 ribosomal frameshifting in yeast cells expressing mutant forms of ribosomal protein L3 are unable to maintain the dsRNA “Killer” virus. Here we demonstrate that changes in frameshifting and virus maintenance in these mutants correlates with decreased peptidyltransferase activities. The mutants did not affect Ty1-directed programmed +1 ribosomal frameshifting or nonsense-mediated mRNA decay. Independent experiments demonstrate similar programmed −1 ribosomal frameshifting specific defects in cells lacking ribosomal protein L41, which has previously been shown to result in peptidyltransferase defects in yeast. These findings are consistent with the hypothesis that decreased peptidyltransferase activity should result in longer ribosome pause times after the accommodation step of the elongation cycle, allowing more time for ribosomal slippage at programmed −1 ribosomal frameshift signals.",,"['MESKAUSKAS, ARTURAS', 'HARGER, JASON W.', 'MULDOON JACOBS, KRISTI L.', 'DINMAN, JONATHAN D.']",,,,
,PMC,Short term outcome and risk factors for adverse clinical outcomes in adults with severe acute respiratory syndrome (SARS),http://dx.doi.org/10.1136/thorax.58.8.686,PMC1746764,,,"Background: Severe acute respiratory syndrome (SARS) was diagnosed in Hong Kong in over 1700 patients between March and early June 2003. Methods: 115 patients diagnosed with SARS were admitted to Queen Elizabeth Hospital, a large regional hospital in Hong Kong, from March 2003, of whom 100 were either discharged or were dead at 31 May. The patients were prospectively studied after admission to assess their short term outcomes and the risk factors associated with adverse outcomes, defined as death or the need for mechanical ventilation Results: At the time of writing 18 patients had died, with a crude mortality rate of 15.7% and a 21 day mortality of 10% (standard error 3%). Thirty nine patients (34%) were admitted to the intensive care unit, 30 of whom (26%) required mechanical ventilation. Multivariate analysis showed that age above 60 (hazards ratio (HR) 3.5, 95% CI 1.2 to 10.2; p=0.02), presence of diabetes mellitus or heart disease (HR 9.1, 95% CI 2.8 to 29.1; p<0.001), and the presence of other comorbid conditions (HR 5.2, 95% CI 1.4 to 19.7; p=0.01) were independently associated with mortality. However, only the presence of diabetes mellitus and/or cardiac disease (HR 7.3, 95% CI 3.1 to 17.4; p<0.001) was associated with adverse outcomes as a whole. Conclusion: SARS is a new disease entity that carries significant morbidity and mortality. Specific clinical and laboratory parameters predicting unfavourable outcomes have been identified.",,"['Chan, J', 'Ng, C', 'Chan, Y', 'Mok, T', 'Lee, S', 'Chu, S', 'Law, W', 'Lee, M', 'Li, P']",,,,
,PMC,Breathing exercises and asthma,http://dx.doi.org/10.1136/thorax.58.8.649,PMC1746759,,,,,"Thomas, M",,,,
,PMC,Closing the NETT on lung volume reduction surgery,http://dx.doi.org/10.1136/thorax.58.8.651,PMC1746757,,,,,"Calverley, P",,,,
,PMC,Where is SARS now?,http://dx.doi.org/10.1136/thorax.58.8.650,PMC1746755,,,,,"Openshaw, P",,,,
,PMC,eCMAJ's top 10 — May,,PMC164992,,,,,,,,,
,PMC,Right to refuse work becomes another SARS issue,,PMC164991,,,,,"Sibbald, Barbara",,,,
,PMC,Infection control for the disinterested,,PMC164978,,,,,"['Schull, Michael J.', 'Redelmeier, Donald A.']",,,,
,PMC,WHO Framework Convention on Tobacco Control: development of an evidence  based global public health treaty,,PMC1126513,,,"Many health problems require international action, but getting governments to agree on strategies for prevention or treatment is difficult. By making use of scientific evidence on the effects of tobacco, the member states of WHO have negotiated their first global health treaty. If the treaty can be implemented effectively, it could act as a possible model for tackling other health issues",,"['Shibuya, Kenji', 'Ciecierski, Christina', 'Guindon, Emmanuel', 'Bettcher, Douglas W', 'Evans, David B', 'Murray, Christopher J L']",,,,
,PMC,Lords committee warns of gaps in infection control measures,,PMC1126500,,,,,"Eaton, Lynn",,,,
,PMC,Severe acute respiratory syndrome: patients were epidemiologically  linked,,PMC165702,,,,,,,,,
,PMC,Doctors criticise preparations for bioterrorist attacks,,PMC1150952,,,,,"Beecham, Linda",,,,
,PMC,"WHO says SARS outbreak is over, but fight should go on",,PMC1150938,,,,,"Fleck, Fiona",,,,
,PMC,Homelessness and health,,PMC1126482,,,,,"Tayal, Upasana",,,,
,PMC,A step backward,,PMC164934,,,,,"Gorodzinsky, F.P.",,,,
,PMC,What's in a name?,,PMC164931,,,,,"Sullivan, Patrick",,,,
,PMC,What's in a name?,,PMC164930,,,,,"Nadasdi, Miklos",,,,
,PMC,Viral lower respiratory tract infection in infants and young children,,PMC1126381,,,,,"['van Woensel, J B M', 'van Aalderen, W M C', 'Kimpen, J L L']",,,,
,PMC,In brief,,PMC1126373,,,,,,,,,
,PMC,John Lawson--an appreciation.,,PMC1314668,,,,,"McKinlay, David",,,,
,PMC,The future of academic primary care.,,PMC1314664,,,,,"Hannay, David",,,,
,PMC,SARS revisited.,,PMC1314663,,,,,"Moore, Michael",,,,
,PMC,Primary care is cost-effective care.,,PMC1314662,,,,,"Ashworth, Andrew J",,,,
,PMC,Special non-clinical interests as career development.,,PMC1314661,,,,,"Carelli, Francesco",,,,
,PMC,Homelessness and primary care.,,PMC1314660,,,,,"Wright, Nat",,,,
,PMC,Recruitment strategies for research.,,PMC1314659,,,,,"['Cross, Pamela L', 'Parsons, Suzanne', 'Letley, Louise']",,,,
,PMC,Definition of diabetes mellitus.,,PMC1314658,,,,,"al-Hassan, Nader",,,,
,PMC,Breach of confidentiality?,,PMC1314657,,,,,"Clarke, Eamonn",,,,
,PMC,Opening Pandora's box.,,PMC1314656,,,,,"Wong, Geoff",,,,
,PMC,Diagnosis of pneumonia.,,PMC1314655,,,,,"Gunstone, Chris",,,,
,PMC,Diagnosis of pneumonia.,,PMC1314654,,,,,"['Brindle, Peter', 'Hay, Alastair D', 'Fahey, Tom']",,,,
,PMC,Infection in Hong Kong.,,PMC1314653,,,,,"Mackay, John",,,,
,PMC,Do patients want copies of referral letters?,,PMC1314651,,,,,"Morrow, Gerry",,,,
,PMC,"New contract, new dilemmas.",,PMC1314650,,,,,"Horne, Dominic",,,,
,PMC,Reflecting on a week just past.,,PMC2214261,,,,,"Rachlis, Val",,,,
,PMC,"Christopher Columbus, King Canute and SARS: the name does matter",http://dx.doi.org/10.7861/clinmedicine.3-4-389,PMC5351963,,,,,,,,,
,PMC,Helicases as Antiviral Drug Targets,,PMC3571683,,,"Helicases catalytically unwind duplex DNA or RNA using energy derived from the hydrolysis of nucleoside triphosphates and are attractive drug targets because they are required for viral replication. This review discusses methods for helicase identification, classification and analysis, and presents an overview of helicases that are necessary for the replication of human pathogenic viruses. Newly developed methods to analyze helicases, coupled with recently determined atomic structures, have led to a better understanding of their mechanisms of action. The majority of this research has concentrated on enzymes encoded by the herpes simplex virus (HSV) and the hepatitis C virus (HCV). Helicase inhibitors that target the HSV helicase–primase complex comprised of the UL5, UL8 and UL52 proteins have recently been shown to effectively control HSV infection in animal models. In addition, several groups have reported structures of the HCV NS3 helicase at atomic resolutions, and mechanistic studies have uncovered characteristics that distinguish the HCV helicase from related cellular proteins. These new developments should eventually lead to new antiviral medications.",,"Frick, David N.",,,,
,PMC,Health is a global issue,http://dx.doi.org/10.1038/sj.embor.embor892,PMC1326331,,,The SARS epidemic was a wake-up call for public health authorities worldwide about the threat of emerging infectious diseases,,"Brower, Vicki",,,,
,PMC,A new infectious disease challenge: Urbani severe acute respiratory syndrome (SARS) associated coronavirus,http://dx.doi.org/10.1046/j.1365-2567.2003.01684.x,PMC1782984,,,,,"['Oxford, J S', 'Bossuyt, S', 'Lambkin, R']",,,,
,PMC,DNA vaccines and apoptosis: to kill or not to kill?,http://dx.doi.org/10.1172/JCI200319069,PMC162296,,,"The apoptotic machinery has become the latest target of vaccinologists attempting to improve the efficacy of DNA vaccines. While workers have previously sought to induce apoptotic death in transfected DCs as a means to activate immunity, a new approach (see related article on pages 109–117) instead seeks to delay apoptosis in host DCs after DNA vaccination.",,"['Leitner, Wolfgang W.', 'Restifo, Nicholas P.']",,,,
,PMC,The Fgl2/fibroleukin prothrombinase contributes to immunologically mediated thrombosis in experimental and human viral hepatitis,http://dx.doi.org/10.1172/JCI200318114,PMC162293,,,"Fibrin deposition and thrombosis within the microvasculature is now appreciated to play a pivotal role in the hepatocellular injury observed in experimental and human viral hepatitis. Importantly, the pathways by which fibrin generation is elicited in viral hepatitis may be mechanistically distinct from the classical pathways of coagulation induced by mechanical trauma or bacterial lipopolysaccharide (LPS). In the setting of murine hepatitis virus strain-3 (MHV-3) infection, a member of the Coronaviridae, activated endothelial cells and macrophages express distinct cell-surface procoagulants, including a novel prothrombinase, Fgl2/fibroleukin, which are important for both the initiation and localization of fibrin deposition. To assess the role of Fgl2/fibroleukin in murine viral hepatitis we generated a Fgl2/fibroleukin–deficient mouse. Peritoneal macrophages isolated from Fgl2/fibroleukin(–/–) mice did not generate a procoagulant response when infected with MHV-3. Fibrin deposition and liver necrosis were markedly reduced, and survival was increased in mice infected with MHV-3. To address the relevance of Fgl2/fibroleukin in human chronic viral hepatitis we studied patients with minimal and marked chronic hepatitis B. We detected robust expression of Fgl2/fibroleukin mRNA transcripts and protein in liver tissue isolated from patients with marked chronic hepatitis B. Fibrin deposition was strongly associated with Fgl2/fibroleukin expression. Collectively, these data indicate a critical role for Fgl2/fibroleukin in the pathophysiology of experimental and human viral hepatitis.",,"['Marsden, Philip A.', 'Ning, Qin', 'Fung, Laisum S.', 'Luo, Xioping', 'Chen, Yue', 'Mendicino, Michael', 'Ghanekar, Anand', 'Scott, Jeremy A.', 'Miller, Teresa', 'Chan, Camie W.Y.', 'Chan, Mathew W.C.', 'He, Wei', 'Gorczynski, Reginald M.', 'Grant, David R.', 'Clark, David A.', 'Phillips, M. James', 'Levy, Gary A.']",,,,
,PMC,Reverse Transcription-PCR Assays for Detection of Bovine Enteric Caliciviruses (BEC) and Analysis of the Genetic Relationships among BEC and Human Caliciviruses,http://dx.doi.org/10.1128/JCM.41.7.3089-3099.2003,PMC165218,,,"Two genetically distinct bovine enteric caliciviruses (BECs) have been identified: the norovirus (NLV) Jena and Newbury Agent-2 (NA-2) BECs, which are genetically related to human noroviruses, and the Nebraska (NB) BECs, which is related to sapoviruses and lagoviruses but may also represent a new calicivirus genus. The prevalence of these two BEC genotypes in cattle is unknown. Although reverse transcription-PCR (RT-PCR) primers for human NLV recognize NLV-BECs, the genetic relationships between NLV from humans and the NLV-BECs commonly circulating in cattle is undefined. In the present study, veal calf fecal samples were assayed for enteric caliciviruses by using six RT-PCR primer sets designed for the detection of human NLVs or BECs. Caliciviruses genetically related to the NLV-BEC Jena and NA-2 strains or to the recently characterized NB BEC strain were identified in three of four and four of four sampled veal herds, respectively. Extended 3′-terminal genome sequences of two NLV-BECs, designated CV95-OH and CV186-OH, encoding the RNA-dependent RNA polymerase (RdRp; open reading frame 1 [ORF-1]), VP1 (ORF-2), and VP2 (ORF-3) genes were determined. Phylogenetic and sequence identity analyses of each genome region demonstrated these viruses to be most closely related to the NLV-BEC Jena and NA-2 strains. In initial testing, the human P289-P290 (P289/290) primer set was found to be the most sensitive for calicivirus detection. However, its failure to identify all positive fecal pools (as determined by other assays) led us to design two new primer sets, CBECU-F/R and NBU-F/R, for the sensitive and specific detection of NLV-BEC (NLV-BEC Jena and NA-2) and BEC-NB-like viruses, respectively. The RT-PCR assays with the new primers were compared against other primer sets, including P289/290. Composite results of the tests completed by using the new assays identified 72% (54 of 75) of veal calf fecal samples as positive, with 21 of 21 sequenced reaction products specific for the target RdRp gene. The same design strategy used for the new BEC assays may also be applicable to the design of similar assays for the detection of human caliciviruses (HuCVs). Our data support the genetic relationship between NLV-BECs and NLV-HuCVs but with the NLV-BECs comprising two clusters within a third NLV genogroup.",,"['Smiley, J. R.', 'Hoet, A. E.', 'Tråvén, M.', 'Tsunemitsu, H.', 'Saif, L. J.']",,,,
,PMC,In the Wake of Terror,,PMC539550,,,,,"Kessel, Ross",,,,
,PMC,Identification of the Murine Coronavirus MP1 Cleavage Site Recognized by Papain-Like Proteinase 2,http://dx.doi.org/10.1128/JVI.77.13.7376-7382.2003,PMC164800,,,"The replicase polyprotein of murine coronavirus is extensively processed by three proteinases, two papain-like proteinases (PLPs), termed PLP1 and PLP2, and a picornavirus 3C-like proteinase (3CLpro). Previously, we established a trans-cleavage assay and showed that PLP2 cleaves the replicase polyprotein between p210 and membrane protein 1 (MP1) (A. Kanjanahaluethai and S. C. Baker, J. Virol. 74:7911-7921, 2000). Here, we report the results of our studies identifying and characterizing this cleavage site. To determine the approximate position of the cleavage site, we expressed constructs that extended various distances upstream from the previously defined C-terminal end of MP1. We found that the construct extending from the putative PLP2 cleavage site at glycine 2840-alanine 2841 was most similar in size to the processed MP1 replicase product generated in a trans-cleavage assay. To determine which amino acids are critical for PLP2 recognition and processing, we generated 14 constructs with amino acid substitutions upstream and downstream of the putative cleavage site and assessed the effects of the mutations in the PLP2 trans-cleavage assay. We found that substitutions at phenylalanine 2835, glycine 2839, or glycine 2840 resulted in a reduction in cleavage of MP1. Finally, to unequivocally identify this cleavage site, we isolated radiolabeled MP1 protein and determined the position of [(35)S]methionine residues released by Edman degradation reaction. We found that the amino-terminal residue of MP1 corresponds to alanine 2841. Therefore, murine coronavirus PLP2 cleaves the replicase polyprotein between glycine 2840 and alanine 2841, and the critical determinants for PLP2 recognition and processing occupy the P6, P2, and P1 positions of the cleavage site. This study is the first report of the identification and characterization of a cleavage site recognized by murine coronavirus PLP2 activity.",,"['Kanjanahaluethai, Amornrat', 'Jukneliene, Dalia', 'Baker, Susan C.']",,,,
,PMC,Variable Sensitivity to Substitutions in the N-Terminal Heptad Repeat of Mason-Pfizer Monkey Virus Transmembrane Protein,http://dx.doi.org/10.1128/JVI.77.14.7779-7785.2003,PMC161947,,,"The transmembrane protein of Mason-Pfizer monkey virus contains two heptad repeats that are predicted to form amphipathic α-helices that mediate the conformational change necessary for membrane fusion. To analyze the relative sensitivity of the predicted hydrophobic face of the N-terminal heptad repeat to the insertion of uncharged, polar, and charged substitutions, mutations that introduced alanine, serine, or glutamic acid into positions 436, 443, 450, and 457 of the envelope protein were examined. Novel systems using Tat protein and the GHOST cell line were developed to test and quantitate the effects of the mutations on Env-mediated fusion and infectivity of the virus. While no single amino acid change at any of the positions interfered significantly with the synthesis, processing, or transport to the plasma membrane of glycoprotein complexes, 9 of the 12 nonconservative mutations in these residues completely abolished fusion activity and virus infectivity. Mutations in the central positions (443 and 450) of the heptad repeat region were the most detrimental to Env function, and even single alanine substitutions in these positions dramatically altered the fusogenicity of the protein. These results demonstrate that this N-terminal heptad repeat plays a critical role in Env-mediated membrane fusion and highlight the key function of central hydrophobic residues in this process and the sensitivity of all positions to charge substitutions.",,"['Song, Chisu', 'Hunter, Eric']",,,,
,PMC,Transmissible Gastroenteritis Coronavirus Packaging Signal Is Located at the 5′ End of the Virus Genome,http://dx.doi.org/10.1128/JVI.77.14.7890-7902.2003,PMC161917,,,"To locate the transmissible gastroenteritis coronavirus (TGEV) packaging signal, the incorporation of TGEV subgenomic mRNAs (sgmRNAs) into virions was first addressed. TGEV virions were purified by three different techniques, including an immunopurification using an M protein-specific monoclonal antibody. Detection of sgmRNAs in virions by specific reverse transcription-PCRs (RT-PCRs) was related to the purity of virus preparations. Interestingly, virus mRNAs were detected in partially purified virus but not in virus immunopurified using stringent conditions. Analyses by quantitative RT-PCR confirmed that virus mRNAs were not present in highly purified preparations. Lack of sgmRNA encapsidation was probably due to the absence of a packaging signal (Ψ) within these mRNAs. This information plus that from the encapsidation of a collection of TGEV-derived minigenomes suggested that Ψ is located at the 5′ end of the genome. To confirm that this was the case, a set of minigenomes was expressed that included an expression cassette for an mRNA including the β-glucuronidase gene (GUS) plus variable sequence fragments from the 5′ end of the virus genome potentially including Ψ. Insertion of the first 649 nucleotides (nt) of the TGEV genome led to the specific encapsidation of the mRNA, indicating that a Ψ was located within this region which was absent from all of the other virus mRNAs. The presence of this packaging signal was further confirmed by showing the expression and rescue of the mRNA including the first 649 nt of the TGEV genome under control of the cytomegalovirus promoter in TGEV-infected cells. This mRNA was successfully amplified and encapsidated, indicating that the first 649 nt of TGEV genome also contained the 5′ cis-acting replication signals. The encapsidation efficiency of this mRNA was about 30-fold higher than the genome encapsidation efficiency, as estimated by quantitative RT-PCR. In contrast, viral mRNAs presented significantly lower encapsidation efficiencies (about 100-fold) than those of the virus genome, strongly suggesting that TGEV mRNAs in fact lacked an alternative TGEV Ψ.",,"['Escors, David', 'Izeta, Ander', 'Capiscol, Carmen', 'Enjuanes, Luis']",,,,
,PMC,An outbreak of SARS among healthcare workers,http://dx.doi.org/10.1136/oem.60.7.528,PMC1740572,,,,,"Wong, T. W.",,,,
,PMC,Facts and ideas from anywhere,,PMC1200797,,,,,"Roberts, William C.",,,,
,PMC,Invited commentary: Preventing colon cancer: looking over the horizon,,PMC1200790,,,,,"['Boland, C. Richard', 'Demarco, Daniel C.']",,,,
,PMC,Role of the endothelium and nitric oxide synthases in modulating superoxide formation induced by endotoxin and cytokines in porcine pulmonary arteries,http://dx.doi.org/10.1136/thorax.58.7.598,PMC1746752,,,"Methods: Intrapulmonary artery (PA) segments were obtained from White Landrace pigs (25–35 kg) and incubated with LPS, IL-1α, and TNF-α and O(2)(• -) release was measured by the superoxide dismutase (SOD) inhibitable reduction of ferricytochrome c. The source of O(2)(• -) formation was determined using a number of enzyme inhibitors. The role of NO was explored using NO synthase (NOS) inhibitors and the distribution of NOS isoforms and peroxynitrite (ONOO(-), an index of NO–O(2)(• -) interactions) assessed by immunocytochemistry. Results: LPS, IL-1α, and TNF-α promoted the formation of O(2)(• -) from PA compared with untreated controls in a time and dose dependent manner, an effect markedly enhanced by removal of the endothelium but completely inhibited by the NADPH oxidase inhibitor diphenylene iodonium chloride (DPI). L-NAME and the eNOS inhibitor N(5)-(1-iminoethyl)-ornithine (L-NIO) enhanced O(2)(• -) formation from PA (with endothelium) in response to IL-1α and TNF-α but had no effect on LPS mediated O(2)(• -) formation, whereas L-NAME and the iNOS inhibitor L-N(6)-(1-iminoethyl)-lysine-HCl (L-NIL) enhanced O(2)(• -) formation only in response to LPS. Conclusions: LPS, IL-1α, and TNF-α promote O(2)(• -) formation through an upregulation of NADPH oxidase activity which is augmented by removal of the endothelium, as well as the inhibition of eNOS (in the case of cytokines) and iNOS (in the case of LPS). The concomitant expression of NOS isoforms (and NO formation) with that of NADPH oxidase may therefore constitute a protective system designed to remove O(2)(• -) through the formation of ONOO(-). If this is so, the integrity of the endothelium may be axiomatic in the progression and severity of ARDS.",,"['Muzaffar, S', 'Jeremy, J', 'Angelini, G', 'Stuart-Smith, K', 'Shukla, N']",,,,
,PMC,ACE in COPD: a therapeutic target?,http://dx.doi.org/10.1136/thorax.58.7.556,PMC1746750,,,,,"['Forth, R', 'Montgomery, H']",,,,
,PMC,The SARS epidemic: emergence of a new respiratory virus?,http://dx.doi.org/10.1136/thorax.58.7.604,PMC1746748,,,,,"Seemungal, T",,,,
,PMC,"Severe acute respiratory syndrome (SARS): epidemiology, diagnosis and management",http://dx.doi.org/10.1136/thorax.58.7.558,PMC1746727,,,,,"['Wong, G', 'Hui, D']",,,,
,PMC,SARS and Population Health Technology,http://dx.doi.org/10.2196/jmir.5.2.e14,PMC1550560,12857670,CC BY,"The recent global outbreak of SARS (severe acute respiratory syndrome) provides an opportunity to study the use and impact of public health informatics and population health technology to detect and fight a global epidemic. Population health technology is the umbrella term for technology applications that have a population focus and the potential to improve public health. This includes the Internet, but also other technologies such as wireless devices, mobile phones, smart appliances, or smart homes. In the context of an outbreak or bioterrorism attack, such technologies may help to gather intelligence and detect diseases early, and communicate and exchange information electronically worldwide. Some of the technologies brought forward during the SARS epidemic may have been primarily motivated by marketing efforts, or were more directed towards reassuring people that ""something is being done,"" ie, fighting an ""epidemic of fear."" To understand ""fear epidemiology"" is important because early warning systems monitoring data from a large number of people may not be able to discriminate between a biological epidemic and an epidemic of fear. The need for critical evaluation of all of these technologies is stressed.",2003 Jun 30,"Eysenbach, Gunther",J Med Internet Res,,,
,PMC,NETLINES,,PMC1126352,,,,,"Brown, Harry",,,,
,PMC,Clinical course and management of SARS in health care workers in Toronto: a case series,,PMC161610,,,"BACKGROUND: Severe acute respiratory syndrome (SARS) has only recently been described. We provide individual patient data on the clinical course, treatment and complications experienced by 14 front-line health care workers and hospital support staff in Toronto who were diagnosed with SARS, and we provide follow-up information for up to 3 weeks after their discharge from hospital. METHODS: As part of the initial response to the SARS outbreak in Toronto, our health care centre was asked to establish a SARS unit for health care workers who were infected. Patients were admitted to this unit and were closely monitored and treated until they were well enough to be discharged. We prospectively compiled information on their clinical course, management and complications and followed them for 3 weeks after discharge. RESULTS: The 11 women and 3 men described here (mean age 42 [standard deviation {SD} 9] years) were all involved in providing medical or ancillary hospital services to patients who were later found to have SARS. Onset of symptoms in 4 of our patients who could clearly identify only a single contact with a patient with SARS occurred on average 4 (SD 3) days after exposure. For the remaining 10 patients with multiple patient contacts, symptom onset followed exposure by a mean of 3.5 (SD 3) days after their exposure. All patients were treated with ribavirin, and all patients received levofloxacin. Many experienced major complications. Dyspnea was present in 12 patients during their stay in hospital, and all developed abnormalities on chest radiograph; 3 patients developed severe hypoxemia (PaO(2) < 50 mm Hg). All patients experienced a drop in hemoglobin. Nine patients had hemolytic anemia. Three patients experienced numbness and tingling in their hands and feet, and 2 developed frank tetany. All 3 had magnesium levels that were less than 0.1 mmol/L. All patients recovered and were discharged home. At a follow-up examination 3 weeks after discharge (5 weeks after onset of illness), all patients were no longer weak but continued to become fatigued easily and had dyspnea on minimal exertion. For 5 patients, chest radiographs still showed residual disease. INTERPRETATION: SARS is a very serious illness even in healthy, relatively young people. The clinical course in our patients, all of whom met the case definition for SARS (which requires pulmonary involvement), resulted in dyspnea and, in some individuals, severe hypoxemia. Severe hemolytic anemia may be a feature of SARS or may be a complication of therapy, possibly with ribavirin.",,"['Avendano, Monica', 'Derkach, Peter', 'Swan, Susan']",,,,
,PMC,Highlights of this issue,,PMC161598,,,,,,,,,
,PMC,Scientific publishing picks up speed,,PMC161597,,,,,,,,,
,PMC,WHO praises China's control measures for SARS,,PMC1151021,,,,,"Parry, Jane",,,,
,PMC,SARS art,,PMC1126290,,,,,"Jackson, Trevor",,,,
,PMC,SARS Reference,,PMC1126287,,,"Eds Bernd Sebastian Kamps, Christian Hoffmann Flying Publisher, pp 85 Available to download for free at http://SARSreference.com/ Rating: ★★★",,"Maskalyk, James",,,,
,PMC,Severe acute respiratory syndrome: Threat of tuberculosis  persists,,PMC1126267,,,,,"Davies, Peter D O",,,,
,PMC,Severe acute respiratory syndrome: Lessons may be learnt from the  outbreak of legionnaires' disease in Barrow in Furness,,PMC1126266,,,,,"['Smith, Andrew F', 'Wild, Cathy', 'Law, John']",,,,
,PMC,Severe acute respiratory syndrome: Capture-recapture method should be  used to count how many cases of SARS really exist,,PMC1126265,,,,,"['Lange, John H', 'LaPorte, Ronald E']",,,,
,PMC,Severe acute respiratory syndrome: Numbers do not tell whole  story,,PMC1126264,,,,,"['Hsieh, Ying-Hen', 'Chen, Cathy Woan-Shu']",,,,
,PMC,Severe acute respiratory syndrome: Guidelines were drawn up  collaboratively to protect healthcare workers in British Columbia,,PMC1126263,,,,,"['Yassi, Annalee', 'Noble, Michael A', 'Daly, Patricia', 'Bryce, Elizabeth']",,,,
,PMC,Severe acute respiratory syndrome: Private hospital in Singapore took  effective control measures,,PMC1126262,,,,,"['Yeoh, S C', 'Lee, E', 'Lee, B W', 'Goh, D L']",,,,
,PMC,Severe acute respiratory syndrome: Clinical outcome after inpatient  outbreak of SARS in Singapore,,PMC1126261,,,,,"['Tan, Yu-Meng', 'Chow, Pierce KH', 'Soo, Khee-Chee']",,,,
,PMC,Severe acute respiratory syndrome: Imported cases of severe acute  respiratory syndrome to Singapore had impact on national epidemic,,PMC1126260,,,,,"['Wilder-Smith, Annelies', 'Paton, Nicholas I']",,,,
,PMC,Severe acute respiratory syndrome: Patients were epidemiologically  linked,,PMC1126259,,,,,"['Chan-Yeung, Moira', 'Seto, Wing Hong', 'Sung, Joseph J Y']",,,,
,PMC,Haematological manifestations in patients with severe acute respiratory  syndrome: retrospective analysis,,PMC162124,,,"Objectives To evaluate the haematological findings of patients with severe acute respiratory syndrome (SARS). Design Analysis of the demographic, clinical, and laboratory characteristics of patients with SARS. Setting Prince of Wales Hospital, Hong Kong. Subjects All patients with a diagnosis of SARS between 11 March and 29 March 2003 who had no pre-existing haematological disorders. Main outcome measures Clinical end points included the need for intensive care and death. Univariate and multivariate analyses were performed to examine factors associated with adverse outcome. Results 64 male and 93 female patients were included in this study. The most common findings included lymphopenia in 153 (98%) of the 157 patients, neutrophilia in 129 (82%), thrombocytopenia in 87 patients (55%), followed by thrombocytosis in 77 (49%), and isolated prolonged activated partial thromboplastin time in 96 patients (63%). The haemoglobin count dropped by more than 20 g/l from baseline in 95 (61%) patients. Four patients (2.5%) developed disseminated intravascular coagulation. Lymphopenia was shown in haemato-lymphoid organs at postmortem examination. Multivariate analysis showed that advanced age and a high concentration of lactate dehydrogenase at presentation were independent predictors of an adverse outcome. Subsets of peripheral blood lymphocytes were analysed in 31 patients. The counts of CD4 positive and CD8 positive T cells fell early in the course of illness. Low counts of CD4 and CD8 cells at presentation were associated with adverse outcomes. Conclusions Abnormal haematological variables were common among patients with SARS. Lymphopenia and the depletion of T lymphocyte subsets may be associated with disease activity.",,"['Wong, Raymond S M', 'Wu, Alan', 'To, K F', 'Lee, Nelson', 'Lam, Christopher W K', 'Wong, C K', 'Chan, Paul K S', 'Ng, Margaret H L', 'Yu, L M', 'Hui, David S', 'Tam, John S', 'Cheng, Gregory', 'Sung, Joseph J Y']",,,,
,PMC,Evaluation of WHO criteria for identifying patients with severe acute  respiratory syndrome out of hospital: prospective observational study,,PMC162123,,,"Objectives To determine the clinical and radiological features of severe acute respiratory syndrome (SARS) and to evaluate the accuracy of the World Health Organization's guidelines on defining cases of SARS. Design Prospective observational study. Setting A newly set up SARS screening clinic in the emergency department of a university hospital in Hong Kong's New Territories. Participants 556 hospital staff, patients, and relatives who attended the screening clinic and who had had contact with someone with SARS. Main outcome measure Number of confirmed cases of SARS. Results Of the 556 people, 141 were admitted to hospital, and 97 had confirmed SARS. Fever, chills, malaise, myalgia, rigor, loss of appetite, vomiting, diarrhoea, and neck pain but not respiratory tract symptoms were significantly more common among the 97 patients than among the other patients. The overall accuracy of the WHO guidelines for identifying suspected SARS was 83% and their negative predictive value was 86% (95% confidence interval 83% to 89%). They had a sensitivity of 26% (17% to 36%) and a specificity of 96% (93% to 97%). Conclusions Current WHO guidelines for diagnosing suspected SARS may not be sufficiently sensitive in assessing patients before admission to hospital. Daily follow up, evaluation of non-respiratory, systemic symptoms, and chest radiography would be better screening tools.",,"['Rainer, Timothy H', 'Cameron, Peter A', 'Smit, DeVilliers', 'Ong, Kim L', 'Hung, Alex Ng Wing', 'Nin, David Chan Po', 'Ahuja, Anil T', 'Si, Louis Chan Yik', 'Sung, Joseph J Y']",,,,
,PMC,Advances in clinical diagnosis and treatment of severe acute respiratory syndrome,http://dx.doi.org/10.3748/wjg.v9.i6.1139,PMC4611773,,,"It has been proved that severe acute respiratory syndrome (SARS) is caused by SARS-associated coronavirus, a novel coronavirus. SARS originated in Guangdong Province, the People's Republic of China at the end of 2002. At present, it has spread to more than 33 countries or regions all over the world and affected 8360 people and killed 764 by May 31, 2003. Identification of the SARS causative agent and development of a diagnostic test are important. Detecting disease in its early stage, understanding its pathways of transmission and implementing specific prevention measures for the disease are dependent upon swift progress. Due to the efforts of the WHO-led network of laboratories testing for SARS, tests for the novel coronavirus have been developed with unprecedented speed. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses. WHO established the definitions of suspected and confirmed and probable cases. But the laboratory tests and definitions are limited. Until now, the primary measures included isolation, ribavirin and corticosteroid therapy, mechanical ventilation, etc. Other therapies such as convalescent plasma are being explored. It is necessary to find more effective therapy. There still are many problems to be solved in the course of conquering SARS.",,"['Nie, Qing-He', 'Luo, Xin-Dong', 'Hui, Wu-Li']",,,,
,PMC,Severe acute respiratory syndrome and its lesions in digestive system,http://dx.doi.org/10.3748/wjg.v9.i6.1135,PMC4611772,,,"Severe acute respiratory syndrome (SARS) is an infectious atypical pneumonia that has recently been recognized in the patients in 32 countries and regions. This brief review summarizes some of the initial etiologic findings, pathological description, and its lesions of digestive system caused by SARS virus. It is an attempt to draw gastroenterologists and hepatologists' attention to this fatal illness, especially when it manifests itself initially as digestive symptoms.",,"Zhang, Jian-Zhong",,,,
,PMC,WHO investigates China's fall in SARS cases,,PMC1126174,,,,,"Parry, Jane",,,,
,PMC,Will SARS crisis give Canada its own CDC?,,PMC156698,,,,,"Wharry, Steve",,,,
,PMC,Updated SARS case definition using laboratory criteria,,PMC156690,,,,,"Hoey, John",,,,
,PMC,The best protection,,PMC156669,,,,,"Lange, John H.",,,,
,PMC,Bush legislates for $15bn to be spent on AIDS,,PMC1150998,,,,,"Gottlieb, Scott",,,,
,PMC,Spread of SARS slows,,PMC1150996,,,,,"Parry, Jane",,,,
,PMC,The Back Pages,,PMC1314638,,,,,,,,,
,PMC,"Special non-clinical interests--GPs in education, research, and management.",,PMC1314616,,,,,"['Howe, Amanda', 'Baker, Maureen', 'Field, Steve', 'Pringle, Mike']",,,,
,PMC,Re-evaluating revalidation and appraisal.,,PMC1314615,,,,,"Pringle, Mike",,,,
,PMC,The doctor as an educator.,,PMC1314614,,,,,"Dawes, Martin",,,,
,PMC,"Severe acute respiratory syndrome--novel virus, recurring theme.",,PMC1314613,,,,,"['Harnden, Anthony', 'Mayon-White, Richard']",,,,
,PMC,"Out with the old, in with the new!",,PMC2214239,,,,,"Malkin, Lilia",,,,
,PMC,Answers to Quiz Corner,,PMC340184,,,,,,,,,
,PMC,QUIZ CORNER,,PMC340161,,,,,,,,,
,PMC,HIV and AIDS in relation to other pandemics,http://dx.doi.org/10.1038/sj.embor.embor857,PMC1326444,,,"Among the viruses plaguing humans, HIV is a recent acquisition. Its outstanding success as an infection poses immense scientific challenges to human health and raises the question “What comes next?”",,"Weiss, Robin A.",,,,
,PMC,SARS coronavirus: a new challenge for prevention and therapy,http://dx.doi.org/10.1172/JCI200318819,PMC156116,,,,,"Holmes, Kathryn V.",,,,
,PMC,SARS has Health Officials Worried,,PMC2594529,,,,,"Dawson, George A.",,,,
,PMC,The Impact of SARS on Childbirth Education,http://dx.doi.org/10.1624/105812403X106919,PMC1595163,,,The SARS (Severe Acute Respiratory Syndrome) crisis in Toronto in the spring of 2003 had major consequences for prenatal learners. Classes in hospitals were cancelled; many couples were left without any prenatal education. This paper outlines the decision-making process of one programme that was determined to keep classes open. The impact of SARS on hospital procedures is also described. Childbirth educators are encouraged to prepare for future public health emergencies. Strategies to prepare for conducting childbirth education classes during times of crisis are outlined.,,"Midmer, Deana",,,,
,PMC,Stem-Loop III in the 5′ Untranslated Region Is a cis-Acting Element in Bovine Coronavirus Defective Interfering RNA Replication,http://dx.doi.org/10.1128/JVI.77.12.6720-6730.2003,PMC156170,,,"Higher-order structures in the 5′ untranslated region (UTR) of plus-strand RNA viruses are known in many cases to function as cis-acting elements in RNA translation, replication, or transcription. Here we describe evidence supporting the structure and a cis-acting function in defective interfering (DI) RNA replication of stem-loop III, the third of four predicted higher-order structures mapping within the 210-nucleotide (nt) 5′ UTR of the 32-kb bovine coronavirus (BCoV) genome. Stem-loop III maps at nt 97 through 116, has a calculated free energy of −9.1 kcal/mol in the positive strand and −3.0 kcal/mol in the negative strand, and has associated with it beginning at nt 100 an open reading frame (ORF) potentially encoding an 8-amino-acid peptide. Stem-loop III is presumed to function in the positive strand, but its strand of action has not been established. Stem-loop III (i) shows phylogenetic conservation among group 2 coronaviruses and appears to have a homolog in coronavirus groups 1 and 3, (ii) has in all coronaviruses for which sequence is known a closely associated short, AUG-initiated intra-5′ UTR ORF, (iii) is supported by enzyme structure-probing evidence in BCoV RNA, (iv) must maintain stem integrity for DI RNA replication in BCoV DI RNA, and (v) shows a positive correlation between maintenance of the short ORF and maximal DI RNA accumulation in BCoV DI RNA. These results indicate that stem-loop III in the BCoV 5′ UTR is a cis-acting element for DI RNA replication and that its associated intra-5′ UTR ORF may function to enhance replication. It is postulated that these two elements function similarly in the virus genome.",,"['Raman, Sharmila', 'Bouma, Peter', 'Williams, Gwyn D.', 'Brian, David A.']",,,,
,PMC,A New Sendai Virus Vector Deficient in the Matrix Gene Does Not Form Virus Particles and Shows Extensive Cell-to-Cell Spreading,http://dx.doi.org/10.1128/JVI.77.11.6419-6429.2003,PMC155001,,,"A new recombinant Sendai virus vector (SeV/ΔM), in which the gene encoding matrix (M) protein was deleted, was recovered from cDNA and propagated in a packaging cell line expressing M protein by using a Cre/loxP induction system. The titer of SeV/ΔM carrying the enhanced green fluorescent protein gene in place of the M gene was 7 × 10(7) cell infectious units/ml or more. The new vector showed high levels of infectivity and gene expression, similar to those of wild-type SeV vector, in vitro and in vivo. Virus maturation into a particle was almost completely abolished in cells infected with SeV/ΔM. Instead, SeV/ΔM infection brought about a significant increase of syncytium formation under conditions in which the fusion protein was proteolytically cleaved and activated by trypsin-like protease. This shows that SeV/ΔM spreads markedly to neighboring cells in a cell-to-cell manner, because both hemagglutinin-neuraminidase and active fusion proteins are present at very high levels on the surface of cells infected with SeV/ΔM. Thus, SeV/ΔM is a novel type of vector with the characteristic features of loss of virus particle formation and gain of cell-to-cell spreading via a mechanism dependent on the activation of the fusion protein.",,"['Inoue, Makoto', 'Tokusumi, Yumiko', 'Ban, Hiroshi', 'Kanaya, Takumi', 'Shirakura, Masayuki', 'Tokusumi, Tsuyoshi', 'Hirata, Takahiro', 'Nagai, Yoshiyuki', 'Iida, Akihiro', 'Hasegawa, Mamoru']",,,,
,PMC,West Nile Virus Infection in the United States: Overview as a Public Health Issue,,PMC3111822,,,"In August 1999, West Nile virus (WNV), a mosquito-transmitted flavivirus, appeared in New York City. This represented the first time a major outbreak of this Old World virus caused an epidemic in the western hemisphere. By December 2002, the outbreak had spread, probably via avian migratory flyways, to involve 44 states and the District of Columbia. The future epidemiology of WNV infection in the United States will be difficult to forecast. In the absence of an effective human vaccine, the only means of prevention and control is reducing contact between humans and infected mosquitoes. An effective public health infrastructure will be critical in monitoring the progress of this epidemic and developing a strategy to control it.",,"Dalovisio, Joseph R.",,,,
,PMC,New WHO chief pledges to expand network to stem disease outbreaks,,PMC1174774,,,,,"Fleck, Fiona",,,,
,PMC,WHO continues fight against SARS,,PMC1174770,,,,,"González Aguirre,  Adrián",,,,
,PMC,Data show that SARS is gradually coming under control,,PMC1174769,,,,,"Parry, Jane",,,,
,PMC,Toronto succumbs to SARS a second time,,PMC1126042,,,,,"Spurgeon, David",,,,
,PMC,"SARS may have a silver lining, WHO says",,PMC155978,,,,,"Nadamuni, Sridhar",,,,
,PMC,SARS poses challenges for MDs treating pediatric patients,,PMC155976,,,,,"Mackay, Brad",,,,
,PMC,"As SARS toll climbed, so did economic cost to Toronto",,PMC155974,,,,,"Mackay, Brad",,,,
,PMC,Why was Toronto included in the World Health Organization's SARS-related travel advisory?,,PMC155962,,,,,"Rodier, Guénaël R.M.",,,,
,PMC,"SARS: prudence, not panic",,PMC155961,,,,,"Schabas, Richard",,,,
,PMC,Identification and containment of an outbreak of SARS in a community hospital,,PMC155957,,,"BACKGROUND: Severe acute respiratory syndrome (SARS) is continuing to spread around the world. All hospitals must be prepared to care for patients with SARS. Thus, it is important to understand the transmission of this disease in hospitals and to evaluate methods for its containment in health care institutions. We describe how we cared for the first 2 patients with SARS admitted to our 419-bed community hospital in Richmond Hill, Ont., and the response to a SARS outbreak within our institution. METHODS: We collected clinical and epidemiological data about patients and health care workers at our institution who during a 13-day period had a potential unprotected exposure to 2 patients whose signs and symptoms were subsequently identified as meeting the case definition for probable SARS. The index case at our hospital was a patient who was transferred to our intensive care unit (ICU) from a referral hospital on Mar. 16, 2003, where he had been in close proximity to the son of the individual with the first reported case of SARS in Toronto. After 13 days in the ICU, a diagnosis of probable SARS was reached for our index case. Immediately upon diagnosis of our index case, respiratory isolation and barrier precautions were instituted throughout our hospital and maintained for a period of 10 days, which is the estimated maximum incubation period reported for this disease. Aggressive surveillance measures among hospital staff, patients and visitors were also maintained during this time. RESULTS: During the surveillance period, 15 individuals (10 hospital staff, 3 patients and 2 visitors) were identified as meeting the case definition for probable or suspected SARS, in addition to our index case. All but 1 individual had had direct contact with a symptomatic patient with SARS during the period of unprotected exposure. No additional cases were identified after infection control precautions had been implemented for 8 days. No cases of secondary transmission were identified in the 21 days following the implementation of these precautions at our institution. INTERPRETATION: SARS can easily be spread by direct personal contact in the hospital setting. We found that the implementation of aggressive infection control measures is effective in preventing further transmission of this disease.",,"['Dwosh, Hy A.', 'Hong, Harry H.L.', 'Austgarden, Douglas', 'Herman, Stanley', 'Schabas, Richard']",,,,
,PMC,Highlights of this issue,,PMC155938,,,,,,,,,
,PMC,Lessons from SARS,,PMC155937,,,,,,,,,
,PMC,Chinese scientists must test wild animals to find the host of SARS,,PMC1150989,,,,,"Gottlieb, Scott",,,,
,PMC,SARS revisited,,PMC514082,,,,,"Waechter, Fabian",,,,
,PMC,Chinese scientists must test wild animals to find the host of SARS,,PMC514042,,,,,"Gottlieb, Scott",,,,
,PMC,United Kingdom has its first confirmed case of SARS,,PMC514033,,,,,"Parry, Jane",,,,
,PMC,US and Germany give late support to WHO tobacco accord,,PMC514032,,,,,"Fleck, Fiona",,,,
,PMC,Transmission Dynamics and Control of Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1126/science.1086616,PMC2760158,,,"Severe acute respiratory syndrome (SARS) is a recently described illness of humans that has spread widely over the past 6 months. With the use of detailed epidemiologic data from Singapore and epidemic curves from other settings, we estimated the reproductive number for SARS in the absence of interventions and in the presence of control efforts. We estimate that a single infectious case of SARS will infect about three secondary cases in a population that has not yet instituted control measures. Public-health efforts to reduce transmission are expected to have a substantial impact on reducing the size of the epidemic.",,"['Lipsitch, Marc', 'Cohen, Ted', 'Cooper, Ben', 'Robins, James M.', 'Ma, Stefan', 'James, Lyn', 'Gopalakrishna, Gowri', 'Chew, Suok Kai', 'Tan, Chorh Chuan', 'Samore, Matthew H.', 'Fisman, David', 'Murray, Megan']",,,,
,PMC,SARS in China spreads from Beijing to poorer inland provinces,,PMC1150975,,,,,"Parry, Jane",,,,
,PMC,United States and Germany are keen to see tobacco agreement watered down,,PMC1150972,,,,,"Watson, Rory",,,,
,PMC,China in the grip of SARS,,PMC1126024,,,,,"Hesketh, Therese",,,,
,PMC,Hit Parade,,PMC1126021,,,,,,,,,
,PMC,Medicine in the time of SARS,,PMC1125986,,,,,"Hui, Andrew C F",,,,
,PMC,"China is still not open enough about SARS, says WHO",,PMC1125983,,,,,"Parry, Jane",,,,
,PMC,SARS' financial impact on hospitals still being tallied,,PMC154207,,,,,"Mackay, Brad",,,,
,PMC,SARS: “a domino effect through entire system”,,PMC154202,,,,,"Mackay, Brad",,,,
,PMC,SARS update,,PMC154192,,,,,"Hoey, John",,,,
,PMC,Ribavirin in the treatment of SARS: A new trick for an old drug?,,PMC154189,,,,,"['Koren, Gideon', 'King, Susan', 'Knowles, Sandra', 'Phillips, Elizabeth']",,,,
,PMC,The race to outpace severe acute respiratory syndrome (SARS),,PMC154183,,,,,"Patrick, David M.",,,,
,PMC,Containing a new infection with new technology: a Web-based response to SARS,,PMC154181,,,,,"['VanDenKerkhof, Elizabeth G.', 'Goldstein, David H.', 'Rimmer, Michael J.']",,,,
,PMC,The immediate psychological and occupational impact of the 2003 SARS outbreak in a teaching hospital,,PMC154178,,,"BACKGROUND: The outbreak of severe acute respiratory syndrome (SARS) in Toronto, which began on Mar. 7, 2003, resulted in extraordinary public health and infection control measures. We aimed to describe the psychological and occupational impact of this event within a large hospital in the first 4 weeks of the outbreak and the subsequent administrative and mental health response. METHODS: Two principal authors met with core team members and mental health care providers at Mount Sinai Hospital, Toronto, to compile retrospectively descriptions of the experiences of staff and patients based on informal observation. All authors reviewed and analyzed the descriptions in an iterative process between Apr. 3 and Apr. 13, 2003. RESULTS: In a 4-week period, 19 individuals developed SARS, including 11 health care workers. The hospital's response included establishing a leadership command team and a SARS isolation unit, implementing mental health support interventions for patients and staff, overcoming problems with logistics and communication, and overcoming resistance to directives. Patients with SARS reported fear, loneliness, boredom and anger, and they worried about the effects of quarantine and contagion on family members and friends. They experienced anxiety about fever and the effects of insomnia. Staff were adversely affected by fear of contagion and of infecting family, friends and colleagues. Caring for health care workers as patients and colleagues was emotionally difficult. Uncertainty and stigmatization were prominent themes for both staff and patients. INTERPRETATION: The hospital's response required clear communication, sensitivity to individual responses to stress, collaboration between disciplines, authoritative leadership and provision of relevant support. The emotional and behavioural reactions of patients and staff are understood to be a normal, adaptive response to stress in the face of an overwhelming event.",,"['Maunder, Robert', 'Hunter, Jonathan', 'Vincent, Leslie', 'Bennett, Jocelyn', 'Peladeau, Nathalie', 'Leszcz, Molyn', 'Sadavoy, Joel', 'Verhaeghe, Lieve M.', 'Steinberg, Rosalie', 'Mazzulli, Tony']",,,,
,PMC,Highlights of this issue,,PMC154160,,,,,,,,,
,PMC,SARS: the struggle for containment,,PMC154159,,,,,,,,,
,PMC,Toronto strives for normality after WHO lifts travel warning,,PMC1169358,,,,,"Spurgeon, David",,,,
,PMC,Containment of SARS depends on how it is handled in China,,PMC1169357,,,,,"Parry, Jane",,,,
,PMC,WHO warns that death rate from SARS could reach 10%,,PMC1125964,,,,,"Parry, Jane",,,,
,PMC,Two strains of the SARS virus sequenced,,PMC1125963,,,,,"Dyer, Owen",,,,
,PMC,,,PMC1125910,,,,,,,,,
,PMC,"SARS could still affect the United Kingdom, health secretary warns",,PMC1125874,,,,,"Eaton, Lynn",,,,
,PMC,Canada insists that it is a safe place to visit,,PMC1125873,,,,,"Spurgeon, David",,,,
,PMC,"SARS may have peaked in Canada, Hong Kong, and Vietnam",,PMC1125871,,,,,"Parry, Jane",,,,
,PMC,Tropical Travel and Life-Threatening Disease: Preventing Malaria Misadventures,,PMC2094933,,,,,"McCarthy, Anne E",,,,
,PMC,A SARS commentary,,PMC2094928,,,,,"Nicolle, Lindsay",,,,
,PMC,SARS : A Tale of Two Epidemics,,PMC2094926,,,,,"['Conly, John M', 'Johnston, B Lynn']",,,,
,PMC,In Vitro and In Ovo Expression of Chicken Gamma Interferon by a Defective RNA of Avian Coronavirus Infectious Bronchitis Virus,http://dx.doi.org/10.1128/JVI.77.10.5694-5702.2003,PMC154032,,,"Coronavirus defective RNAs (D-RNAs) have been used for site-directed mutagenesis of coronavirus genomes and for expression of heterologous genes. D-RNA CD-61 derived from the avian coronavirus infectious bronchitis virus (IBV) was used as an RNA vector for the expression of chicken gamma interferon (chIFN-γ). D-RNAs expressing chIFN-γ were shown to be capable of rescue, replication, and packaging into virions in a helper virus-dependent system following electroporation of in vitro-derived T7 RNA transcripts into IBV-infected cells. Secreted chIFN-γ, under the control of an IBV transcription-associated sequence derived from gene 5 of the Beaudette strain, was expressed from two different positions within CD-61 and shown to be biologically active. In addition, following infection of 10-day-old chicken embryos with IBV containing D-RNAs expressing chIFN-γ, the allantoic fluid was shown to contain biologically active chIFN-γ, demonstrating that IBV D-RNAs can express heterologous genes in vivo.",,"['Hackney, Karen', 'Cavanagh, Dave', 'Kaiser, Pete', 'Britton, Paul']",,,,
,PMC,Topology of the Membrane-Associated Hepatitis C Virus Protein NS4B,http://dx.doi.org/10.1128/JVI.77.9.5428-5438.2003,PMC153960,,,"Hepatitis C virus (HCV) belongs to the Hepacivirus genus in the Flaviviridae family. Among the least known viral proteins in this family is the nonstructural protein NS4B, which has been suggested to be a part of the replication complex. Hydrophobicity plots indicate a common profile among the NS4B proteins from different members of the Flaviviridae family, suggesting a common function. In order to gain a deeper understanding of the nature of HCV NS4B, we have determined localization and topology of this protein by using recombinant HCV NS4B constructs. The protein localized to the endoplasmic reticulum (ER), but also induced a pattern of cytoplasmic foci positive for markers of the ER. Computer predictions of the membrane topology of NS4B suggested that it has four transmembrane segments. The N and C termini were anticipated to be localized in the cytoplasm, because they are processed by the cytoplasmic NS3 protein. By introducing glycosylation sites at various positions in HCV NS4B, we show that the C terminus is cytoplasmic and the loop around residue 161 is lumenal as predicted. Surprisingly, the N-terminal tail was translocated into the lumen in a considerable fraction of the NS4B molecules, most likely by a posttranslational process. Interestingly, NS4B proteins of the yellow fever and dengue viruses also have their N termini located in the ER lumen due to an N-terminal signal peptide not found in NS4B of HCV. A shared topology achieved in two different ways supports the notion of a common function for NS4B in Flaviviridae.",,"['Lundin, Marika', 'Monné, Magnus', 'Widell, Anders', 'von Heijne, Gunnar', 'Persson, Mats A. A.']",,,,
,PMC,Human Papillomavirus Type 16 E7 Peptide-Directed CD8(+) T Cells from Patients with Cervical Cancer Are Cross-Reactive with the Coronavirus NS2 Protein,http://dx.doi.org/10.1128/JVI.77.9.5464-5474.2003,PMC153943,,,"Human papillomavirus type 16 (HPV16) E6 and E7 oncoproteins are required for cellular transformation and represent candidate targets for HPV-specific and major histocompatibility complex class I-restricted CD8(+)-T-cell responses in patients with cervical cancer. Recent evidence suggests that cross-reactivity represents the inherent nature of the T-cell repertoire. We identified HLA-A2 binding HPV16 E7 variant peptides from human, bacterial, or viral origin which are able to drive CD8(+)-T-cell responses directed against wild-type HPV16 E7 amino acid 11 to 19/20 (E7(11-19/20)) epitope YMLDLQPET(T) in vitro. CD8(+) T cells reacting to the HLA-A2-presented peptide from HPV16 E7(11-19(20)) recognized also the HLA-A2 binding peptide TMLDIQPED (amino acids 52 to 60) from the human coronavirus OC43 NS2 gene product. Establishment of coronavirus NS2-specific, HLA-A2-restricted CD8(+)-T-cell clones and ex vivo analysis of HPV16 E7 specific T cells obtained by HLA-A2 tetramer-guided sorting from PBL or tumor-infiltrating lymphocytes obtained from patients with cervical cancer showed that cross-reactivity with HPV16 E7(11-19(20)) and coronavirus NS2(52-60) represents a common feature of this antiviral immune response defined by cytokine production. Zero of 10 patients with carcinoma in situ neoplasia and 3 of 18 patients with cervical cancer showed ≥0.1% HPV16 E7-reactive T cells in CD8(+) peripheral blood lymphocytes. In vivo priming with HPV16 was confirmed in patients with cervical cancer or preinvasive HPV16-positive lesions using HLA-A2 tetramer complexes loaded with the E6-derived epitope KLPQLCTEL. In contrast, we could not detect E6-reactive T cells in healthy individuals. These data imply that the measurement of the HPV16 E7(11-19(20)) CD8(+)-T-cell response may reflect cross-reactivity with a common pathogen and that variant peptides may be employed to drive an effective cellular immune response against HPV.",,"['Nilges, Katja', 'Höhn, Hanni', 'Pilch, Henryk', 'Neukirch, Claudia', 'Freitag, Kirsten', 'Talbot, P. J.', 'Maeurer, Markus J.']",,,,
,PMC,eCMAJ's SARS section proves popular,,PMC153698,,,,,,,,,
,PMC,Explosion of internet advertisements for protection against SARS,,PMC1157071,,,,,"Charatan, Fred",,,,
,PMC,How popular perceptions of risk from SARS  are fermenting discrimination,,PMC1125856,,,,,"Schram, Justin",,,,
,PMC,Time to show unity against SARS,,PMC1125854,,,,,"Chao, David",,,,
,PMC,Severe acute respiratory syndrome,,PMC1125853,,,,,"Jackson, Trevor",,,,
,PMC,The other war,,PMC1125852,,,,,"Kirk, Richard",,,,
,PMC,Policies on SARS in UK boarding schools are confused,,PMC1125832,,,,,"Wong, Ian",,,,
,PMC,Canada reports more than 300 suspected cases of SARS,,PMC1125815,,,,,"Spurgeon, David",,,,
,PMC,"SARS virus identified, but the disease is still spreading",,PMC1125814,,,,,"Parry, Jane",,,,
,PMC,SARS shows no sign of coming under control,,PMC1125766,,,,,"Parry, Jane",,,,
,PMC,"Severe acute respiratory syndrome revisited : Coronavirus may be responsible, but new information arrives every day",,PMC1125755,,,,,"Zambon, Maria",,,,
,PMC,"After war, plague",,PMC1125753,,,,,"Smith, Richard",,,,
,PMC,Severe acute respiratory syndrome demands strict control,,PMC1125747,,,,,,,,,
,PMC,Outbreak of severe acute respiratory syndrome in Hong Kong Special Administrative Region: case report,,PMC153470,,,"OBJECTIVE: To describe the outbreak of severe acute respiratory syndrome in Hong Kong. DESIGN: Descriptive case series. SETTING: Hong Kong, Special Administrative Region, China RESULTS: The outbreak started with a visitor from southern China on 21 February. At the hospitals where the first cases were treated the disease spread quickly among healthcare workers, and then out into the community as family members became infected. By 1 April, 685 cases had been reported with 16 deaths. Symptoms include high fever and one or more respiratory symptoms (including cough, shortness of breath, and difficulty breathing). Changes in lung tissue suggest that part of the lung damage is due to cytokines induced by the microbial agent, which has led to empirical treatment with corticosteroids, broad spectrum antiviral agent, and antibacterial cover. There is strong evidence that a novel coronavirus is the pathogen. Precautions for droplet infection should be instituted, including the wearing of masks and rigorous disinfection and hygiene procedures. On 27 March the Department of Health announced drastic measures, including vigorous contact tracing and examination, quarantine of contacts in their homes, and closure of all schools and universities. CONCLUSION: The rapidity of the spread of the disease and the morbidity indicate that the agent responsible is highly infectious and virulent. Strict infection control measures for droplet and contact transmission by healthcare workers, a vigilant healthcare profession, and public education are essential for disease prevention.",,"['Chan-Yeung, Moira', 'Yu, W C']",,,,
,PMC,Severe acute respiratory syndrome,,PMC152686,,,,,"Hoey, John",,,,
,PMC,Fear of SARS thwarts medical education in Toronto,,PMC1169342,,,,,"Clark, Jocalyn",,,,
,PMC,Carlo Urbani,,PMC1125733,,,,,"Fleck, Fiona",,,,
,PMC,China joins global effort over pneumonia virus,,PMC1125705,,,,,"Parry, Jane",,,,
,PMC,Hong Kong and US scientists believe illness is a coronavirus,,PMC1125641,,,,,"Parry, Jane",,,,
,PMC,Krüppel Cripples Prostate Cancer : KLF6 Progress and Prospects,,PMC1851219,,,,,"['Narla, Goutham', 'Friedman, Scott L.', 'Martignetti, John A.']",,,,
,PMC,Importance of Respiratory Viruses in Acute Otitis Media,http://dx.doi.org/10.1128/CMR.16.2.230-241.2003,PMC153141,,,"Acute otitis media is usually considered a simple bacterial infection that is treated with antibiotics. However, ample evidence derived from studies ranging from animal experiments to extensive clinical trials supports a crucial role for respiratory viruses in the etiology and pathogenesis of acute otitis media. Viral infection of the upper respiratory mucosa initiates the whole cascade of events that finally leads to the development of acute otitis media as a complication. The pathogenesis of acute otitis media involves a complex interplay between viruses, bacteria, and the host’s inflammatory response. In a substantial number of children, viruses can be found in the middle-ear fluid either alone or together with bacteria, and recent studies indicate that at least some viruses actively invade the middle ear. Viruses appear to enhance the inflammatory process in the middle ear, and they may significantly impair the resolution of otitis media. Prevention of the predisposing viral infection by vaccination against the major viruses would probably be the most effective way to prevent acute otitis media. Alternatively, early treatment of the viral infection with specific antiviral agents would also be effective in reducing the occurrence of acute otitis media.",,"['Heikkinen, Terho', 'Chonmaitree, Tasnee']",,,,
,PMC,Murine Coronavirus-Induced Hepatitis: JHM Genetic Background Eliminates A59 Spike-Determined Hepatotropism,http://dx.doi.org/10.1128/JVI.77.8.4972-4978.2003,PMC152168,,,"Recombinant murine coronaviruses, differing only in the spike gene and containing the strain A59 (moderately hepatotropic) and JHM (neurotropic) spike genes in the background of the JHM genome, were compared for the ability to replicate in the liver and induce hepatitis in weanling C57BL/6 mice. Interestingly, expression of the A59 spike glycoprotein within the background of the neurotropic JHM strain does not reproduce the A59 hepatotropic phenotype. Thus, the JHM genetic background plays a dominant role over the spike in the determination of hepatotropism.",,"['Navas, Sonia', 'Weiss, Susan R.']",,,,
,PMC,Homo-Oligomerization of the Porcine Reproductive and Respiratory Syndrome Virus Nucleocapsid Protein and the Role of Disulfide Linkages,http://dx.doi.org/10.1128/JVI.77.8.4546-4557.2003,PMC152152,,,"As a step toward understanding the assembly pathway of the porcine reproductive and respiratory syndrome virus (PRRSV), the oligomeric properties of the nucleocapsid (N) protein were investigated. In this study, we have demonstrated that under nonreducing conditions the N protein forms disulfide-linked homodimers. However, inclusion of an alkylating agent (N-ethylmaleimide [NEM]) prevented disulfide bond formation, suggesting that these intermolecular disulfide linkages were formed as a result of spurious oxidation during cell lysis. In contrast, N protein homodimers isolated from extracellular virions were shown to have formed NEM-resistant intermolecular disulfide linkages, the function of which is probably to impart stability to the virion. Pulse-chase analysis revealed that N protein homodimers become specifically disulfide linked within the virus-infected cell, albeit at the later stages of infection, conceivably when the virus particle buds into the oxidizing environment of the endoplasmic reticulum. Moreover, NEM-resistant disulfide linkages were shown to occur only during productive PRRSV infection, since expression of recombinant N protein did not result in the formation of NEM-resistant disulfide-linked homodimers. Mutational analysis indicated that of the three conserved cysteine residues in the N protein, only the cysteine at position 23 was involved in the formation of disulfide linkages. The N protein dimer was shown to be stable both in the presence and absence of intermolecular disulfide linkages, indicating that noncovalent interactions also play a role in dimerization. Non-disulfide-mediated N protein interactions were subsequently demonstrated both in vitro by the glutathione S-transferase (GST) pull-down assay and in vivo by the mammalian two-hybrid assay. Using a series of N protein deletion mutants fused to GST, amino acids 30 to 37 were shown to be essential for N-N interactions. Furthermore, since RNase A treatment markedly decreased N protein-binding affinity, it appears that at least in vitro, RNA may be involved in bridging N-N interactions. In cross-linking experiments, the N protein was shown to assemble into higher-order structures, including dimers, trimers, tetramers, and pentamers. Together, these findings demonstrate that the N protein possesses self-associative properties, and these likely provide the basis for PRRSV nucleocapsid assembly.",,"['Wootton, Sarah K.', 'Yoo, Dongwan']",,,,
,PMC,Control of Central Nervous System Viral Persistence by Neutralizing Antibody,http://dx.doi.org/10.1128/JVI.77.8.4670-4678.2003,PMC152147,,,"Replication of the neurotropic JHM strain of mouse hepatitis virus within the central nervous system is controlled by cellular immunity. However, following initial clearance, virus reactivates in the absence of humoral immunity. Viral recrudescence is prevented by the transfer of antiviral antibody (Ab). To characterize the specificity and biological functions of Ab critical for maintaining viral persistence, monoclonal Abs specific for the viral spike, matrix, and nucleocapsid proteins were transferred into infected B-cell-deficient mice following initial virus clearance. Neutralizing immunoglobulin G (IgG) but not IgA anti-spike Ab suppressed virus recrudescence, reduced viral antigen in most cell types except oligodendroglia, and was associated with reduced demyelination. Nonneutralizing monoclonal Abs specific for the spike, matrix, and nucleocapsid proteins did not prevent recrudescence, demonstrating that neutralization is critical for maintaining JHM mouse hepatitis virus persistence within the central nervous system. Ab-mediated protection was not associated with alterations in virus-specific T-cell function or inflammation. Furthermore, neutralizing Ab delayed but did not prevent virus recrudescence. These data indicate that following acute viral clearance cellular immunity is ineffective in controlling virus recrudescence and suggest that the continued presence of neutralizing Ab is the essential effector in maintaining viral persistence within the central nervous system.",,"['Ramakrishna, Chandran', 'Bergmann, Cornelia C.', 'Atkinson, Roscoe', 'Stohlman, Stephen A.']",,,,
,PMC,The Small Envelope Protein E Is Not Essential for Murine Coronavirus Replication,http://dx.doi.org/10.1128/JVI.77.8.4597-4608.2003,PMC152126,,,"The importance of the small envelope (E) protein in the assembly of coronaviruses has been demonstrated in several studies. While its precise function is not clearly defined, E is a pivotal player in the morphogenesis of the virion envelope. Expression of the E protein alone results in its incorporation into vesicles that are released from cells, and the coexpression of the E protein with the membrane protein M leads to the assembly of coronavirus-like particles. We have previously generated E gene mutants of mouse hepatitis virus (MHV) that had marked defects in viral growth and produced virions that were aberrantly assembled in comparison to wild-type virions. We have now been able to obtain a viable MHV mutant in which the entire E gene, as well as the nonessential upstream genes 4 and 5a, has been deleted. This mutant (ΔE) was obtained by a targeted RNA recombination method that makes use of a powerful host range-based selection system. The ΔE mutant produces tiny plaques with an unusual morphology compared to plaques formed by wild-type MHV. Despite its low growth rate and low infectious titer, the ΔE mutant is genetically stable, showing no detectable phenotypic changes after several passages. The properties of this mutant provide further support for the importance of E protein in MHV replication, but surprisingly, they also show that E protein is not essential.",,"['Kuo, Lili', 'Masters, Paul S.']",,,,
,PMC,Switching Species Tropism: an Effective Way To Manipulate the Feline Coronavirus Genome,http://dx.doi.org/10.1128/JVI.77.8.4528-4538.2003,PMC152114,,,"Feline infectious peritonitis virus (FIPV), a coronavirus, is the causative agent of an invariably lethal infection in cats. Like other coronaviruses, FIPV contains an extremely large positive-strand RNA genome of ca. 30 kb. We describe here the development and use of a reverse genetics strategy for FIPV based on targeted RNA recombination that is analogous to what has been described for the mouse hepatitis virus (MHV) (L. Kuo et al., J. Virol. 74:1393-1406, 2000). In this two-step process, we first constructed by targeted recombination a mutant of FIPV, designated mFIPV, in which the ectodomain of the spike glycoprotein was replaced by that of MHV. This switch allowed for the selection of the recombinant virus in murine cells: mFIPV grows to high titers in these cells but has lost the ability to grow in feline cells. In a second, reverse process, mFIPV was used as the recipient, and the reintroduction of the FIPV spike now allowed for selection of candidate recombinants by their regained ability to grow in feline cells. In this fashion, we reconstructed a wild-type recombinant virus (r-wtFIPV) and generated a directed mutant FIPV in which the initiation codon of the nonstructural gene 7b had been disrupted (FIPVΔ7b). The r-wtFIPV was indistinguishable from its parental virus FIPV 79-1146 not only for its growth characteristics in tissue culture but also in cats, exhibiting a highly lethal phenotype. FIPVΔ7b had lost the expression of its 7b gene but grew unimpaired in cell culture, confirming that the 7b glycoprotein is not required in vitro. We establish the second targeted RNA recombination system for coronaviruses and provide a powerful tool for the genetic engineering of the FIPV genome.",,"['Haijema, Bert Jan', 'Volders, Haukeliene', 'Rottier, Peter J. M.']",,,,
,PMC,Engineering the Transmissible Gastroenteritis Virus Genome as an Expression Vector Inducing Lactogenic Immunity,http://dx.doi.org/10.1128/JVI.77.7.4357-4369.2003,PMC150661,,,"The genome of the coronavirus transmissible gastroenteritis virus (TGEV) has been engineered as an expression vector with an infectious cDNA. The vector led to the efficient (>40 μg/10(6) cells) and stable (>20 passages) expression of a heterologous gene (green fluorescent protein [GFP]), driven by the transcription-regulating sequences (TRS) of open reading frame (ORF) 3a inserted in the site previously occupied by the nonessential ORFs 3a and 3b. Expression levels driven by this TRS were higher than those of an expression cassette under the control of regulating sequences engineered with the N gene TRS. The recombinant TGEV including the GFP gene was still enteropathogenic, albeit with a 10- to 10(2)-fold reduction in enteric tissue growth. Interestingly, a specific lactogenic immune response against the heterologous protein has been elicited in sows and their progeny. The engineering of an additional insertion site for the heterologous gene between viral genes N and 7 led to instability and to a new genetic organization of the 3′ end of the recombinant viruses. As a consequence, a major species of subgenomic mRNA was generated from a TRS with the noncanonical core sequence 5′-CUAAAA-3′. Extension of the complementarity between the TRS and sequences at the 3′ end of the viral leader was associated with transcriptional activation of noncanonical core sequences. The engineered vector led to expression levels as high as those of well-established vectors and seems very promising for the development of vaccines and, possibly, for gene therapy.",,"['Sola, Isabel', 'Alonso, Sara', 'Zúñiga, Sonia', 'Balasch, Mónica', 'Plana-Durán, Juan', 'Enjuanes, Luis']",,,,
,PMC,Human Coronavirus 229E: Receptor Binding Domain and Neutralization by Soluble Receptor at 37°C,http://dx.doi.org/10.1128/JVI.77.7.4435-4438.2003,PMC150646,,,"Truncated human coronavirus HCoV-229E spike glycoproteins containing amino acids 407 to 547 bound to purified, soluble virus receptor, human aminopeptidase N (hAPN). Soluble hAPN neutralized the infectivity of HCoV-229E virions at 37°C, but not 4°C. Binding of hAPN may therefore trigger conformational changes in the viral spike protein at 37°C that facilitate virus entry.",,"['Breslin, Jamie J.', 'Mørk, Irene', 'Smith, M. K.', 'Vogel, Lotte K.', 'Hemmila, Erin M.', 'Bonavia, Aurelio', 'Talbot, Pierre J.', 'Sjöström, Hans', 'Norén, Ove', 'Holmes, Kathryn V.']",,,,
,PMC,CC Chemokine Ligand 3 (CCL3) Regulates CD8(+)-T-Cell Effector Function and Migration following Viral Infection,http://dx.doi.org/10.1128/JVI.77.7.4004-4014.2003,PMC150617,,,"Chemokines induce the directional migration of targeted populations of leukocytes during periods of inflammation. Moreover, these molecules also regulate T-cell activation and differentiation following antigenic stimulation. In the present study, the contributions of the CC chemokine ligand 3 (CCL3) to the differentiation and migration of effector T cells in response to viral infection of the central nervous system (CNS) were analyzed. CCL3(−/−) mice infected with mouse hepatitis virus exhibited a significant reduction of virus-specific CD8(+) T cells within the CNS, correlating with delayed viral clearance. Decreased infiltration of CD8(+) T cells into infected CCL3(−/−) mice was associated with enhanced accumulation of primed CD8(+) T cells in cervical lymph nodes. Although virus-specific CD8(+) T cells from CCL3(−/−) mice were CD44(high), they remained CD62L(high) and CD25(low), retained CCR7 expression, and contained limited transcripts of the proinflammatory chemokine receptors CCR5 and CXCR3 compared with virus-specific CD8(+) T cells from CCL3(+/+) mice. Furthermore, the absence of CCL3 impaired the cytokine production and cytolytic activity of CD8(+) T cells. In addition, macrophage accumulation within the CNS was significantly decreased in infected CCL3(−/−) mice, correlating with reduced demyelination. These results suggest that CCL3 not only mediates macrophage chemotaxis but also significantly enhances differentiation of primed CD8(+) T cells into effector cells and their release into circulation, thus potentiating effective migration to the site of infection.",,"['Trifilo, Matthew J.', 'Bergmann, Cornelia C.', 'Kuziel, William A.', 'Lane, Thomas E.']",,,,
,PMC,Improving the care for patients with acute severe respiratory disease,http://dx.doi.org/10.1136/thorax.58.4.285,PMC1746652,,,,,"Elliott, M",,,,
,PMC,Functional analysis of cilia and ciliated epithelial ultrastructure in healthy children and young adults,http://dx.doi.org/10.1136/thorax.58.4.333,PMC1746630,,,"Methods: Ciliated epithelial samples were obtained from 76 children and adult volunteers aged 6 months to 43 years by brushing the inferior nasal turbinate. Beating cilia were recorded using a digital high speed video camera which allowed analysis of ciliary beat pattern and beat frequency. Tissue was fixed for transmission electron microscopy. Results: The mean ciliary beat frequency for the paediatric population (12.8 Hz (95% CI 12.3 to 13.3)) was higher than for the adult group (11.5 Hz (95% CI 10.3 to 12.7 Hz), p<0.01, t test); 10% (range 6–24%) of ciliated edges were found to have areas of dyskinetically beating cilia. All samples had evidence of mild epithelial damage. This reflected changes found in all measurements used for assessment of epithelial damage. Ciliary ultrastructural defects were found in less than 5% of cilia. Conclusion: Normal age related reference ranges have been established for ciliary structure and beat frequency. In a healthy population localised epithelial damage may be present causing areas of ciliary dyskinesia.",,"['Chilvers, M', 'Rutman, A', ""O'Callaghan, C""]",,,,
,PMC,US public health service needs strengthening to fight infectious disease,,PMC1169322,,,,,"Marwick, Charles",,,,
,PMC,Hong Kong virus spreads worldwide,,PMC1125594,,,,,"Parry, Jane",,,,
,PMC,Sudden acute respiratory syndrome : May be a rehearsal for the next influenza pandemic,,PMC1125584,,,,,"['Zambon, Maria', 'Nicholson, Karl G']",,,,
,PMC,UK travellers warned after first suspected case of new syndrome,,PMC1125524,,,,,"Ellis, Anna",,,,
,PMC,WHO issues global alert on respiratory syndrome,,PMC1125523,,,,,"Parry, Jane",,,,
,PMC,Regulation of N-glycolylneuraminic acid biosynthesis in developing pig small intestine.,http://dx.doi.org/10.1042/BJ20021049,PMC1223197,,,"N -Glycolylneuraminic acid (Neu5Gc), an abundant sialic acid in animal glycoconjugates, is formed by the enzyme CMP-N-acetylneuraminic acid (CMP-Neu5Ac) hydroxylase. The amount of Neu5Gc relative to other sialic acids is highly dependent on the species, tissue and developmental stage. Although the activity of the hydroxylase is a key factor in controlling Neu5Gc incorporation in adult animals, little is known about the regulation of hydroxylase expression and the role of this enzyme in determining changes in Neu5Gc during development. Using pig small intestine as a model system, the appearance of total sialic acid and the regulation of Neu5Gc biosynthesis during development were studied in various regions of this tissue. The amount of total sialic acid and Neu5Gc declined markedly in 2 weeks after birth. Although in subsequent developmental phases there were no positional differences in total sialic acid, a significant proximal-to-distal increase in Neu5Gc was detected. In all cases, a good correlation between the amount of Neu5Gc, the activity of the hydroxylase and the level of hydroxylase mRNA was observed. However, Western-blot analysis revealed considerable accumulation of less active enzyme in the post partum period, which persisted until adulthood. No evidence for cytosolic factors influencing the hydroxylase activity or for the formation of truncated enzyme was found, raising the possibility that other regulatory mechanisms are involved. The relevance of these results in the formation of Neu5Gc as a receptor for certain pig enteric pathogens is also discussed.",,"['Malykh, Yanina N', 'King, Timothy P', 'Logan, Elizabeth', 'Kelly, Denise', 'Schauer, Roland', 'Shaw, Lee']",,,,
,PMC,Memory T-cell competition for bone marrow seeding,http://dx.doi.org/10.1046/j.1365-2567.2003.01593.x,PMC1782895,,,"The presence in the bone marrow of memory CD8 T cells is well recognized. However, it is still largely unclear how T-cell migration from the lymphoid periphery to the bone marrow is regulated. In the present report, we show that antigen-specific CD4 T cells, as well as antigen-specific CD8 T cells, localize to the bone marrow of immunized mice, and are sustained there over long periods of time. To investigate the rules governing T-cell migration to the bone marrow, we generated chimeric mice in which the lymphoid periphery contained two genetically or phenotypically distinct groups of T cells, one of which was identical to the host. We then examined whether a distinct type of T cell had an advantage over the others in the colonization of bone marrow. Our results show that whereas ICAM1 and CD18 molecules are both involved in homing to lymph nodes, neither is crucial for T-cell bone marrow colonization. We also observed that memory-phenotype CD44(high) T cells, but not virgin-type CD44(−/low) T cells, preferentially home to the bone marrow upon adoptive transfer to normal young mice, but not to thymectomized old recipients where an existing memory T-cell pool precludes their free access. Thus, T-cell colonization of the bone marrow uses distinct molecules from those implicated in lymph node homing, and is regulated both by the properties of the T cell and by the competitive efficacy of other T cells inhabiting the same, saturable niche. This implies that the homing potential of an individual lymphocyte is not merely an intrinsic property of the cell, but rather a property of the lymphoid system taken as a whole.",,"['Di Rosa, Francesca', 'Santoni, Angela']",,,,
,PMC,Interaction between Porcine Reproductive-Respiratory Syndrome Virus and Bacterial Endotoxin in the Lungs of Pigs: Potentiation of Cytokine Production and Respiratory Disease,http://dx.doi.org/10.1128/JCM.41.3.960-966.2003,PMC150282,,,"Porcine reproductive-respiratory syndrome virus (PRRSV) is a key agent in multifactorial respiratory disease of swine. Intratracheal administration of bacterial lipopolysaccharides (LPSs) to PRRSV-infected pigs results in markedly enhanced respiratory disease, whereas the inoculation of each component alone results in largely subclinical disease. This study examines whether PRRSV-LPS-induced respiratory disease is associated with the excessive production of proinflammatory cytokines in the lungs. Gnotobiotic pigs were inoculated intratracheally with PRRSV and then with LPS at 3, 5, 7, 10, or 14 days of infection and euthanatized 6 h after LPS inoculation. Controls were inoculated with PRRSV or LPS only or with phosphate-buffered saline. Virus titers, (histo)pathological changes in the lungs, numbers of inflammatory cells, and bioactive tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), and IL-6 levels in bronchoalveolar lavage fluids were examined. All pigs inoculated with PRRSV-LPS developed severe respiratory disease, whereas the controls that were inoculated with PRRSV or LPS alone did not. PRRSV infection significantly enhanced cytokine production in response to LPS. Peak TNF-α, IL-1, and IL-6 titers were 10 to 100 times higher in the PRRSV-LPS-inoculated pigs than in the pigs inoculated with PRRSV or LPS alone; and the titers correlated with the respiratory signs. The levels of neutrophil infiltration and the pathological changes detected in the lungs of PRRSV-LPS-inoculated pigs resembled those detected when the effects of PRRSV and LPS inoculated alone are combined, but with no synergistic effects between PRRSV and LPS. These data demonstrate a synergism between PRRSV and LPS in the induction of proinflammatory cytokines and an association between induction of these cytokines and disease.",,"['Van Gucht, Steven', 'Van Reeth, Kristien', 'Pensaert, Maurice']",,,,
,PMC,Nucleocapsid-Independent Specific Viral RNA Packaging via Viral Envelope Protein and Viral RNA Signal,http://dx.doi.org/10.1128/JVI.77.5.2922-2927.2003,PMC149775,,,"For any of the enveloped RNA viruses studied to date, recognition of a specific RNA packaging signal by the virus's nucleocapsid (N) protein is the first step described in the process of viral RNA packaging. In the murine coronavirus a selective interaction between the viral transmembrane envelope protein M and the viral ribonucleoprotein complex, composed of N protein and viral RNA containing a short cis-acting RNA element, the packaging signal, determines the selective RNA packaging into virus particles. In this report we show that expressed coronavirus envelope protein M specifically interacted with coexpressed noncoronavirus RNA transcripts containing the short viral packaging signal in the absence of coronavirus N protein. Furthermore, this M protein-packaging signal interaction led to specific packaging of the packaging signal-containing RNA transcripts into coronavirus-like particles in the absence of N protein. These findings not only highlight a novel RNA packaging mechanism for an enveloped virus, where the specific RNA packaging can occur without the core or N protein, but also point to a new, biologically important general model of precise and selective interaction between transmembrane proteins and specific RNA elements.",,"['Narayanan, Krishna', 'Chen, Chun-Jen', 'Maeda, Junko', 'Makino, Shinji']",,,,
,PMC,"The 5′-End Sequence of the Genome of Aichi Virus, a Picornavirus, Contains an Element Critical for Viral RNA Encapsidation",http://dx.doi.org/10.1128/JVI.77.6.3542-3548.2003,PMC149490,,,"Picornavirus positive-strand RNAs are selectively encapsidated despite the coexistence of viral negative-strand RNAs and cellular RNAs in infected cells. However, the precise mechanism of the RNA encapsidation process in picornaviruses remains unclear. Here we report the first identification of an RNA element critical for encapsidation in picornaviruses. The 5′ end of the genome of Aichi virus, a member of the family Picornaviridae, folds into three stem-loop structures (SL-A, SL-B, and SL-C, from the most 5′ end). In the previous study, we constructed a mutant, termed mut6, by exchanging the seven-nucleotide stretches of the middle part of the stem in SL-A with each other to maintain the base pairings of the stem. mut6 exhibited efficient RNA replication and translation but formed no plaques. The present study showed that in cells transfected with mut6 RNA, empty capsids were accumulated, but few virions containing RNA were formed. This means that mut6 has a severe defect in RNA encapsidation. Site-directed mutational analysis indicated that as the mutated region was narrowed, the encapsidation was improved. As a result, the mutation of the 7 bp of the middle part of the stem in SL-A was required for abolishing the plaque-forming ability. Thus, the 5′-end sequence of the Aichi virus genome was shown to play an important role in encapsidation.",,"['Sasaki, Jun', 'Taniguchi, Koki']",,,,
,PMC,Pneumonia causes panic in Guangdong province,,PMC1125313,,,,,"['Rosling, Lesley', 'Rosling, Mark']",,,,
,PMC,Amino Acid Substitutions in VP2 Residues Contacting Sialic Acid in Low-Neurovirulence BeAn Virus Dramatically Reduce Viral Binding and Spread of Infection,http://dx.doi.org/10.1128/JVI.77.4.2709-2716.2003,PMC141107,,,"Theiler's murine encephalomyelitis viruses (TMEV) consist of two groups, the high- and low-neurovirulence groups, based on lethality in intracerebrally inoculated mice. Low-neurovirulence TMEV result in a persistent central nervous system infection in mice, leading to an inflammatory demyelinating pathology and disease. Low- but not high-neurovirulence strains use sialic acid as an attachment factor. The recent resolution of the crystal structure of the low-neurovirulence DA virus in complex with the sialic acid mimic sialyllactose demonstrated that four capsid residues make contact with sialic acid through noncovalent hydrogen bonds. To systematically test the importance of these sialic acid-binding residues in viral entry and infection, we mutated three VP2 puff B amino acids proposed to make contact with sialic acid and analyzed the consequences of each amino acid substitution on viral entry and spread. The fourth residue is in the VP3-VP1 cleavage dipeptide and could not be mutated. Our data suggest that residues Q2161 and G2174 are directly involved in BeAn virus attachment to sialic acid and that substitutions of these two residues result in the loss of or reduced viral binding and hemagglutination and in the inability to spread among BHK-21 cells. In addition, a gain of function-revertant virus was recovered with the Q2161A mutation after prolonged passage in cells.",,"['Kumar, A. S. Manoj', 'Kallio, Patricia', 'Luo, Ming', 'Lipton, Howard L.']",,,,
,PMC,An Alternate Pathway for Recruiting Template RNA to the Brome Mosaic Virus RNA Replication Complex,http://dx.doi.org/10.1128/JVI.77.4.2568-2577.2003,PMC141102,,,"The multidomain RNA replication protein 1a of brome mosaic virus (BMV), a positive-strand RNA virus in the alphavirus-like superfamily, plays key roles in assembly and function of the viral RNA replication complex. 1a, which encodes RNA capping and helicase-like domains, localizes to endoplasmic reticulum membranes, recruits BMV 2a polymerase and viral RNA templates, and forms membrane-bound, capsid-like spherules in which RNA replication occurs. cis-acting signals necessary and sufficient for RNA recruitment by 1a have been mapped in BMV genomic RNA2 and RNA3. Both signals comprise an extended stem-loop whose apex matches the conserved sequence and structure of the TΨC stem-loop in tRNAs (box B). Mutations show that this box B motif is crucial to 1a responsiveness of wild-type RNA2 and RNA3. We report here that, unexpectedly, some chimeric mRNAs expressing the 2a polymerase open reading frame from RNA2 were recruited by 1a to the replication complex and served as templates for negative-strand RNA synthesis, despite lacking the normally essential, box B-containing 5′ signal. Further studies showed that this template recruitment required high-efficiency translation of the RNA templates. Moreover, multiple small frameshifting insertion or deletion mutations throughout the N-terminal region of the open reading frame inhibited this template recruitment, while an in-frame insertion did not. Providing 2a in trans did not restore template recruitment of RNAs with frameshift mutations. Only those deletions in the N-terminal region of 2a that abolished 2a interaction with 1a abolished template recruitment of the RNA. These and other results indicate that this alternate pathway for 1a-dependent RNA recruitment involves 1a interaction with the translating mRNA via the 1a-interactive N-terminal region of the nascent 2a polypeptide. Interaction with nascent 2a also may be involved in 1a recruitment of 2a polymerase to membranes.",,"['Chen, Jianbo', 'Noueiry, Amine', 'Ahlquist, Paul']",,,,
,PMC,Kinetics of Virus-Specific CD8(+)-T-Cell Expansion and Trafficking following Central Nervous System Infection,http://dx.doi.org/10.1128/JVI.77.4.2775-2778.2003,PMC141092,,,"CD8(+) T cells control acute infection of the central nervous system (CNS) by neurotropic mouse hepatitis virus but do not suffice to achieve sterile immunity. To determine the lag between T-cell priming and optimal activity within the CNS, the accumulation of virus-specific CD8(+) T cells in the CNS relative to that in peripheral lymphoid organs was assessed by using gamma interferon-specific ELISPOT assays and class I tetramer staining. Virus-specific CD8(+) T cells were first detected in the cervical lymph nodes. Expansion in the spleen was delayed and less pronounced but also preceded accumulation in the CNS. The data further suggest peripheral acquisition of cytolytic function, thus enhancing CD8(+)-T-cell effector function upon cognate antigen recognition in the CNS.",,"['Marten, Norman W.', 'Stohlman, Stephen A.', 'Zhou, Jiehao', 'Bergmann, Cornelia C.']",,,,
,PMC,Identification of a Receptor-Binding Domain of the Spike Glycoprotein of Human Coronavirus HCoV-229E,http://dx.doi.org/10.1128/JVI.77.4.2530-2538.2003,PMC141070,,,"Human coronavirus HCoV-229E uses human aminopeptidase N (hAPN) as its receptor (C. L. Yeager et al., Nature 357:420-422, 1992). To identify the receptor-binding domain of the viral spike glycoprotein (S), we expressed soluble truncated histidine-tagged S glycoproteins by using baculovirus expression vectors. Truncated S proteins purified by nickel affinity chromatography were shown to be glycosylated and to react with polyclonal anti-HCoV-229E antibodies and monoclonal antibodies to the viral S protein. A truncated protein (S(547)) that contains the N-terminal 547 amino acids bound to 3T3 mouse cells that express hAPN but not to mouse 3T3 cells transfected with empty vector. Binding of S(547) to hAPN was blocked by an anti-hAPN monoclonal antibody that inhibits binding of virus to hAPN and blocks virus infection of human cells and was also blocked by polyclonal anti-HCoV-229E antibody. S proteins that contain the N-terminal 268 or 417 amino acids did not bind to hAPN-3T3 cells. Antibody to the region from amino acid 417 to the C terminus of S blocked binding of S(547) to hAPN-3T3 cells. Thus, the data suggest that the domain of the spike protein between amino acids 417 and 547 is required for the binding of HCoV-229E to its hAPN receptor.",,"['Bonavia, Aurelio', 'Zelus, Bruce D.', 'Wentworth, David E.', 'Talbot, Pierre J.', 'Holmes, Kathryn V.']",,,,
,PMC,Alphavirus Minus-Strand Synthesis and Persistence in Mouse Embryo Fibroblasts Derived from Mice Lacking RNase L and Protein Kinase R,http://dx.doi.org/10.1128/JVI.77.3.1801-1811.2003,PMC140908,,,"We report our studies to probe the possible role of the host response to double-stranded RNA in cessation of alphavirus minus-strand synthesis. Mouse embryo fibroblasts (MEF) from Mx1-deficient mice that also lack either the protein kinase R (PKR) or the latent RNase L or both PKR and RNase L were screened. In RNase L-deficient but not wild-type or PKR-deficient MEF, there was continuous synthesis of minus-strand templates and the formation of new replication complexes producing viral plus strands. Inhibiting translation caused minus-strand synthesis to stop and a loss of transcription activity of the mature replication complexes. This turnover of replication complexes that were stable in cells containing RNase L suggested that RNase L plays some role, albeit possibly indirect, in the formation of stable replication complexes during alphavirus infection. In addition, confluent monolayers of RNase L-deficient murine cells readily established persistent infections and were not killed. This phenotype is contrary to what has been observed for infection in vertebrate cells with a presumably functional RNase L gene and more resembled alphavirus replication in Aedes mosquito cells, in which the activity of replication complexes making plus stands was also found to decay with inhibition of translation.",,"['Sawicki, Dorothea L.', 'Silverman, Robert H.', 'Williams, Bryan R.', 'Sawicki, Stanley G.']",,,,
,PMC,Interleukin-6 Protects Anterior Horn Neurons from Lethal Virus-Induced Injury,http://dx.doi.org/10.1523/JNEUROSCI.23-02-00481.2003,PMC6741877,,,"We evaluated the role of interleukin-6 (IL-6) in neuronal injury after CNS infection. IL-6(−)(/)(−) and IL-6(+/+) mice of resistant major histocompatibility complex (MHC) H-2(b) haplotype intracerebrally infected with Theiler's virus cleared the infection normally without development of viral persistence, lethal neuronal infection, or late phase demyelination. In contrast, infection of IL-6(−)(/)(−) mice on a susceptible H-2(q) haplotype resulted in frequent deaths and severe neurologic deficits within 2 weeks of infection as compared with infected IL-6(+/+)H-2(q) littermate controls. Morphologic analysis demonstrated dramatic injury to anterior horn neurons of IL-6(−)(/)(−)H-2(q) mice at 12 d after infection. Infectious viral titers in the CNS (brain and spinal cord combined) were equivalent between IL-6(−)(/)(−)H-2(q) and IL-6(+/+)H-2(q) mice. In contrast, more viral RNA was detected in the spinal cord of IL-6(−)(/)(−) mice compared with IL-6(+/+) H-2(q) mice. Virus antigen was localized predominantly to anterior horn cells in infected IL-6(−)(/)(−)H-2(q) mice. IL-6 deletion did not affect the humoral response directed against virus, nor did it affect the expression of CD4, CD8, MHC class I, or MHC class II in the CNS. Importantly, IL-6 was expressed by astrocytes of infected IL-6(+/+)mice but not in astrocytes of IL-6(−)(/)(−) mice or uninfected IL-6(+/+) mice. Furthermore, expression of various chemokines was robust at 12 d after infection in both H-2(b) and H-2(q)IL-6(−)(/)(−)mice, indicating that intrinsic CNS inflammatory responses did not depend on the presence of IL-6. Finally, in vitroanalysis of virus-induced death in neuroblastoma-spinal cord-34 motor neurons and primary anterior horn cell neurons showed that IL-6 exerted a neuroprotective effect. These data support the hypothesis that IL-6 plays a critical role in protecting specific populations of neurons from irreversible injury.",,"['Pavelko, Kevin D.', 'Howe, Charles L.', 'Drescher, Kristen M.', 'Gamez, Jeff D.', 'Johnson, Aaron J.', 'Wei, Tao', 'Ransohoff, Richard M.', 'Rodriguez, Moses']",,,,
,PMC,WHO News.,,PMC2572466,,,,,,,,,
,PMC,Index to volume 81.,,PMC2572390,,,,,,,,,
,PMC,Interferon-gamma levels in nasopharyngeal secretions of infants with respiratory syncytial virus and other respiratory viral infections,http://dx.doi.org/10.1046/j.1365-2249.2003.02039.x,PMC1808612,,,"Respiratory syncytial virus (RSV) infection, one of the most common causes of hospitalization of children in developed countries, has been implicated as a cause of asthma. We aimed to characterize the cytokine profile in nasopharyngeal aspirates (NPAs) taken from infants during upper respiratory tract infection to investigate whether RSV induced a unique immune response as compared with other viruses. Additionally, we sought to determine whether this profile was influenced by the infants' atopic status. A prospective birth cohort of babies at high risk of atopy was recruited. Ratios of a T-helper 1 (Th1) cytokine, interferon gamma (IFN-γ) and a T-helper 2 (Th2)-like cytokine, interleukin-10 (IL-10), in NPAs were determined during episodes of respiratory tract infections in the first year. The viral aetiology of the respiratory tract infections was determined using polymerase chain reaction (PCR), culture and immunofluorescence. Atopic status was ascertained at 1 year of age using skin prick tests. Participants were recruited antenatally and subsequently followed in the community. Sixty babies with one or both parents atopic were enrolled into the study. IFN-γ : IL-10 ratios in NPAs during upper respiratory tract infections and their correlation with viral aetiology and atopic status were the main outcome measures. The mean IFN-γ : IL-10 ratio was significantly lower (due to lower IFN-γ) during RSV infections than during infections with other viruses (P = 0·035). The cytokine ratio, however, did not differ between infants with or without wheeze during URTIs (P = 0·44), or between infants who were atopic or non-atopic (P = 0·49). This study suggests that RSV is associated with lower IFN-γ production in young babies, regardless of their atopic status, compared to upper respiratory tract infections where either another virus is detected or where no viral identification is made.",,"['JOSHI, P', 'SHAW, A', 'KAKAKIOS, A', 'ISAACS, D']",,,,
,PMC,Evaluation of a Human Group A Rotavirus Assay for On-Site Detection of Bovine Rotavirus,http://dx.doi.org/10.1128/JCM.41.1.290-294.2003,PMC149593,,,"Neonatal diarrhea induced by bovine group A rotavirus causes significant economic loss in the dairy and beef industry due to increased morbidity and mortality, treatment costs, and reduced growth rates. The objective of this study was to evaluate a human group A rotavirus assay (ImmunoCardSTAT Rotavirus [ICS-RV]) as an on-site diagnostic test for bovine rotavirus. When used with a collection of bovine diarrhea samples submitted to the Virology Section of the Diagnostic Center for Population and Animal Health at Michigan State University and compared to a bovine group A rotavirus-specific reverse transcription-PCR (RT-PCR), the ICS-RV assay had a sensitivity and specificity of 87.0 and 93.6%, respectively. A commercially available group A rotavirus enzyme-linked immunosorbent assay (ELISA) (Pathfinder; Sanofi Diagnostics, Redmond, Wash.), when used with the same fecal sample collection and compared to the same RT-PCR, had a sensitivity and specificity of 78.3 and 67.7%, respectively. Subsequently, the ICS-RV assay, RT-PCR, and a different commercially available group A rotavirus ELISA (Rotaclone; Meridian Diagnostics, Cincinnati, Ohio) were used to evaluate fecal samples collected from neonatal calves experimentally infected with bovine rotavirus. When diarrheic fecal samples that were positive for bovine rotavirus by RT-PCR were evaluated, the ICS-RV assay and the Rotaclone assay detected bovine rotavirus 85 and 95% of the time, respectively. Based on these studies, the ICS-RV assay appears to be an excellent test for detecting group A bovine rotaviruses. This assay may be useful as an on-site diagnostic test for veterinarians as an aid in the management of bovine neonatal diarrhea.",,"['Maes, Roger K.', 'Grooms, Daniel L.', 'Wise, Annabel G.', 'Han, Cunqin', 'Ciesicki, Valerie', 'Hanson, Lora', 'Vickers, Mary Lynne', 'Kanitz, Charles', 'Holland, Robert']",,,,
,PMC,Molecular Assays for Detection of Human Metapneumovirus,http://dx.doi.org/10.1128/JCM.41.1.100-105.2003,PMC149567,,,"The recent description of the respiratory pathogen human metapneumovirus (hMPV) has highlighted a deficiency in current diagnostic techniques for viral agents associated with acute lower respiratory tract infections. We describe two novel approaches to the detection of viral RNA by use of reverse transcriptase PCR (RT-PCR). The PCR products were identified after capture onto a solid-phase medium by hybridization with a sequence-specific, biotinylated oligonucleotide probe. The assay was applied to the screening of 329 nasopharyngeal aspirates sampled from patients suffering from respiratory tract disease. These samples were negative for other common microbial causes of respiratory tract disease. We were able to detect hMPV sequences in 32 (9.7%) samples collected from Australian patients during 2001. To further reduce result turnaround times we designed a fluorogenic TaqMan oligoprobe and combined it with the existing primers for use on the LightCycler platform. The real-time RT-PCR proved to be highly reproducible and detected hMPV in an additional 6 out of 62 samples (9.6%) tested during the comparison of the two diagnostic approaches. We found the real-time RT-PCR to be the test of choice for future investigation of samples for hMPV due to its speed, reproducibility, specificity, and sensitivity.",,"['Mackay, Ian M.', 'Jacob, Kevin C.', 'Woolhouse, Daniel', 'Waller, Katharine', 'Syrmis, Melanie W.', 'Whiley, David M.', 'Siebert, David J.', 'Nissen, Michael', 'Sloots, Theo P.']",,,,
,PMC,The Stability of the Duplex between Sense and Antisense Transcription-Regulating Sequences Is a Crucial Factor in Arterivirus Subgenomic mRNA Synthesis,http://dx.doi.org/10.1128/JVI.77.2.1175-1183.2003,PMC140805,,,"Subgenomic mRNAs of nidoviruses (arteriviruses and coronaviruses) are composed of a common leader sequence and a “body” part of variable size, which are derived from the 5′- and 3′-proximal part of the genome, respectively. Leader-to-body joining has been proposed to occur during minus-strand RNA synthesis and to involve transfer of the nascent RNA strand from one site in the template to another. This discontinuous step in subgenomic RNA synthesis is guided by short transcription-regulating sequences (TRSs) that are present at both these template sites (leader TRS and body TRS). Sense-antisense base pairing between the leader TRS in the plus strand and the body TRS complement in the minus strand is crucial for strand transfer. Here we show that extending the leader TRS-body TRS duplex beyond its wild-type length dramatically enhanced the subgenomic mRNA synthesis of the arterivirus Equine arteritis virus (EAV). Generally, the relative amount of a subgenomic mRNA correlated with the calculated stability of the corresponding leader TRS-body TRS duplex. In addition, various leader TRS mutations induced the generation of minor subgenomic RNA species that were not detected upon infection with wild-type EAV. The synthesis of these RNA species involved leader-body junction events at sites that bear only limited resemblance to the canonical TRS. However, with the mutant leader TRS, but not with the wild-type leader TRS, these sequences could form a duplex that was stable enough to direct subgenomic RNA synthesis, again demonstrating that the stability of the leader TRS-body TRS duplex is a crucial factor in arterivirus subgenomic mRNA synthesis.",,"['Pasternak, Alexander O.', 'van den Born, Erwin', 'Spaan, Willy J. M.', 'Snijder, Eric J.']",,,,
,PMC,The 3C-Like Proteinase of an Invertebrate Nidovirus Links Coronavirus and Potyvirus Homologs,http://dx.doi.org/10.1128/JVI.77.2.1415-1426.2003,PMC140795,,,"Gill-associated virus (GAV), a positive-stranded RNA virus of prawns, is the prototype of newly recognized taxa (genus Okavirus, family Roniviridae) within the order Nidovirales. In this study, a putative GAV cysteine proteinase (3C-like proteinase [3CL(pro)]), which is predicted to be the key enzyme involved in processing of the GAV replicase polyprotein precursors, pp1a and pp1ab, was characterized. Comparative sequence analysis indicated that, like its coronavirus homologs, 3CL(pro) has a three-domain organization and is flanked by hydrophobic domains. The putative 3CL(pro) domain including flanking regions (pp1a residues 2793 to 3143) was fused to the Escherichia coli maltose-binding protein (MBP) and, when expressed in E. coli, was found to possess N-terminal autoprocessing activity that was not dependent on the presence of the 3CL(pro) C-terminal domain. N-terminal sequence analysis of the processed protein revealed that cleavage occurred at the location (2827)LVTHE↓VRTGN(2836). The trans-processing activity of the purified recombinant 3CL(pro) (pp1a residues 2832 to 3126) was used to identify another cleavage site, (6441)KVNHE↓LYHVA(6450), in the C-terminal pp1ab region. Taken together, the data tentatively identify VxHE↓(L,V) as the substrate consensus sequence for the GAV 3CL(pro). The study revealed that the GAV and potyvirus 3CL(pro)s possess similar substrate specificities which correlate with structural similarities in their respective substrate-binding sites, identified in sequence comparisons. Analysis of the proteolytic activities of MBP-3CL(pro) fusion proteins carrying replacements of putative active-site residues provided evidence that, in contrast to most other 3C/3CL(pro)s but in common with coronavirus 3CL(pro)s, the GAV 3CL(pro) employs a Cys(2968)-His(2879) catalytic dyad. The properties of the GAV 3CL(pro) define a novel RNA virus proteinase variant that bridges the gap between the distantly related chymotrypsin-like cysteine proteinases of coronaviruses and potyviruses.",,"['Ziebuhr, John', 'Bayer, Sonja', 'Cowley, Jeff A.', 'Gorbalenya, Alexander E.']",,,,
,PMC,The N-Terminal Domain of the Murine Coronavirus Spike Glycoprotein Determines the CEACAM1 Receptor Specificity of the Virus Strain,http://dx.doi.org/10.1128/JVI.77.2.841-850.2003,PMC140794,,,"Using isogenic recombinant murine coronaviruses expressing wild-type murine hepatitis virus strain 4 (MHV-4) or MHV-A59 spike glycoproteins or chimeric MHV-4/MHV-A59 spike glycoproteins, we have demonstrated the biological functionality of the N-terminus of the spike, encompassing the receptor binding domain (RBD). We have used two assays, one an in vitro liposome binding assay and the other a tissue culture replication assay. The liposome binding assay shows that interaction of the receptor with spikes on virions at 37°C causes a conformational change that makes the virions hydrophobic so that they bind to liposomes (B. D. Zelus, J. H. Schickli, D. M. Blau, S. R. Weiss, and K. V. Holmes, J. Virol. 77: 830-840, 2003). Recombinant viruses with spikes containing the RBD of either MHV-A59 or MHV-4 readily associated with liposomes at 37°C in the presence of soluble mCEACAM1(a), except for S(4)R, which expresses the entire wild-type MHV-4 spike and associated only inefficiently with liposomes following incubation with soluble mCEACAM1(a). In contrast, soluble mCEACAM1(b) allowed viruses with the MHV-A59 RBD to associate with liposomes more efficiently than did viruses with the MHV-4 RBD. In the second assay, which requires virus entry and replication, all recombinant viruses replicated efficiently in BHK cells expressing mCEACAM1(a). In BHK cells expressing mCEACAM1(b), only viruses expressing chimeric spikes with the MHV-A59 RBD could replicate, while replication of viruses expressing chimeric spikes with the MHV-4 RBD was undetectable. Despite having the MHV-4 RBD, S(4)R replicated in BHK cells expressing mCEACAM1(b); this is most probably due to spread via CEACAM1 receptor-independent cell-to-cell fusion, an activity displayed only by S(4)R among the recombinant viruses studied here. These data suggest that the RBD domain and the rest of the spike must coevolve to optimize function in viral entry and spread.",,"['Tsai, Jean C.', 'Zelus, Bruce D.', 'Holmes, Kathryn V.', 'Weiss, Susan R.']",,,,
,PMC,Conformational Changes in the Spike Glycoprotein of Murine Coronavirus Are Induced at 37°C either by Soluble Murine CEACAM1 Receptors or by pH 8,http://dx.doi.org/10.1128/JVI.77.2.830-840.2003,PMC140793,,,"The spike glycoprotein (S) of the murine coronavirus mouse hepatitis virus (MHV) binds to viral murine CEACAM receptor glycoproteins and causes membrane fusion. On virions, the 180-kDa S glycoprotein of the MHV-A59 strain can be cleaved by trypsin to form the 90-kDa N-terminal receptor-binding subunit (S1) and the 90-kDa membrane-anchored fusion subunit (S2). Incubation of virions with purified, soluble CEACAM1a receptor proteins at 37°C and pH 6.5 neutralizes virus infectivity (B. D. Zelus, D. R. Wessner, R. K. Williams, M. N. Pensiero, F. T. Phibbs, M. deSouza, G. S. Dveksler, and K. V. Holmes, J. Virol. 72:7237-7244, 1998). We used liposome flotation and protease sensitivity assays to investigate the mechanism of receptor-induced, temperature-dependent virus neutralization. After incubation with soluble receptor at 37°C and pH 6.5, virions became hydrophobic and bound to liposomes. Receptor binding induced a profound, apparently irreversible conformational change in S on the viral envelope that allowed S2, but not S1, to be degraded by trypsin at 4°C. Various murine CEACAM proteins triggered conformational changes in S on recombinant MHV strains expressing S glycoproteins of MHV-A59 or MHV-4 (MHV-JHM) with the same specificities as seen for virus neutralization and virus-receptor activities. Increased hydrophobicity of virions and conformational change in S2 of MHV-A59 could also be induced by incubating virions at pH 8 and 37°C, without soluble receptor. Surprisingly, the S protein of recombinant MHV-A59 virions with a mutation, H716D, that precluded cleavage between S1 and S2 could also be triggered to undergo a conformational change at 37°C by soluble receptor at neutral pH or by pH 8 alone. A novel 120-kDa subunit was formed following incubation of the receptor-triggered S(A59)H716D virions with trypsin at 4°C. The data show that unlike class 1 fusion glycoproteins of other enveloped viruses, the murine coronavirus S protein can be triggered to a membrane-binding conformation at 37°C either by soluble receptor at neutral pH or by alkaline pH alone, without requiring previous activation by cleavage between S1 and S2.",,"['Zelus, Bruce D.', 'Schickli, Jeanne H.', 'Blau, Dianna M.', 'Weiss, Susan R.', 'Holmes, Kathryn V.']",,,,
,PMC,Functional Expression of Chemokine Receptor CCR5 on CD4(+) T Cells during Virus-Induced Central Nervous System Disease,http://dx.doi.org/10.1128/JVI.77.1.191-198.2003,PMC140629,,,"Intracranial infection of C57BL/6 mice with mouse hepatitis virus (MHV) results in an acute encephalomyelitis followed by a demyelinating disease similar in pathology to the human disease multiple sclerosis (MS). CD4(+) T cells are important in amplifying demyelination by attracting macrophages into the central nervous system (CNS) following viral infection; however, the mechanisms governing the entry of these cells into the CNS are poorly understood. The role of chemokine receptor CCR5 in trafficking of virus-specific CD4(+) T cells into the CNS of MHV-infected mice was investigated. CD4(+) T cells from immunized CCR5(+/+) and CCR5(−/−) mice were expanded in the presence of the immunodominant epitope present in the MHV transmembrane (M) protein encompassing amino acids 133 to 147 (M133-147). Adoptive transfer of CCR5(+/+)-derived CD4(+) T cells to MHV-infected RAG1(−/−) mice resulted in CD4(+)-T-cell entry into the CNS and clearance of virus from the brain. These mice also displayed robust demyelination correlating with macrophage accumulation within the CNS. Conversely, CD4(+) T cells from CCR5(−/−) mice displayed an impaired ability to traffic into the CNS of MHV-infected RAG1(−/−) recipients, which correlated with increased viral titers, diminished macrophage accumulation, and limited demyelination. Analysis of chemokine receptor mRNA expression by M133-147-expanded CCR5(−/−)-derived CD4(+) T cells revealed reduced expression of CCR1, CCR2, and CXCR3, indicating that CCR5 signaling is important in increased expression of these receptors, which aid in trafficking of CD4(+) T cells into the CNS. Collectively these results demonstrate that CCR5 signaling is important to migration of CD4(+) T cells to the CNS following MHV infection.",,"['Glass, William G.', 'Lane, Thomas E.']",,,,
,PMC,Discontinuous and non-discontinuous subgenomic RNA transcription in a nidovirus,http://dx.doi.org/10.1093/emboj/cdf635,PMC136939,,,"Arteri-, corona-, toro- and roniviruses are evolutionarily related positive-strand RNA viruses, united in the order Nidovirales. The best studied nidoviruses, the corona- and arteriviruses, employ a unique transcription mechanism, which involves discontinuous RNA synthesis, a process resembling similarity-assisted copy-choice RNA recombination. During infection, multiple subgenomic (sg) mRNAs are transcribed from a mirror set of sg negative-strand RNA templates. The sg mRNAs all possess a short 5′ common leader sequence, derived from the 5′ end of the genomic RNA. The joining of the non-contiguous ‘leader’ and ‘body’ sequences presumably occurs during minus-strand synthesis. To study whether toroviruses use a similar transcription mechanism, we characterized the 5′ termini of the genome and the four sg mRNAs of Berne virus (BEV). We show that BEV mRNAs 3–5 lack a leader sequence. Surprisingly, however, RNA 2 does contain a leader, identical to the 5′-terminal 18 residues of the genome. Apparently, BEV combines discontinuous and non-discontinous RNA synthesis to produce its sg mRNAs. Our findings have important implications for the understanding of the mechanism and evolution of nidovirus transcription.",,"['van Vliet, A.L.W.', 'Smits, S.L.', 'Rottier, P.J.M.', 'de Groot, R.J.']",,,,
,PMC,Replication and Clearance of Respiratory Syncytial Virus : Apoptosis Is an Important Pathway of Virus Clearance after Experimental Infection with Bovine Respiratory Syncytial Virus,,PMC1850917,,,"Human respiratory syncytial virus is an important cause of severe respiratory disease in young children, the elderly, and in immunocompromised adults. Similarly, bovine respiratory syncytial virus (BRSV) is causing severe, sometimes fatal, respiratory disease in calves. Both viruses are pneumovirus and the infections with human respiratory syncytial virus and BRSV have similar clinical, pathological, and epidemiological characteristics. In this study we used experimental BRSV infection in calves as a model of respiratory syncytial virus infection to demonstrate important aspects of viral replication and clearance in a natural target animal. Replication of BRSV was demonstrated in the luminal part of the respiratory epithelial cells and replication in the upper respiratory tract preceded the replication in the lower respiratory tract. Virus excreted to the lumen of the respiratory tract was cleared by neutrophils whereas apoptosis was an important way of clearance of BRSV-infected epithelial cells. Neighboring cells, which probably were epithelial cells, phagocytized the BRSV-infected apoptotic cells. The number of both CD4(+) and CD8+ T cells increased during the course of infection, but the T cells were not found between the epithelial cells of the bronchi up until apoptosis was no longer detected, thus in the bronchi there was no indication of direct contact-dependent T-cell-mediated cytotoxicity in the primary infection.",,"['Viuff, Birgitte', 'Tjørnehøj, Kirsten', 'Larsen, Lars E.', 'Røntved, Christine M.', 'Uttenthal, Åse', 'Rønsholt, Leif', 'Alexandersen, Soren']",,,,
,PMC,Binding of Norwalk Virus-Like Particles to ABH Histo-Blood Group Antigens Is Blocked by Antisera from Infected Human Volunteers or Experimentally Vaccinated Mice,http://dx.doi.org/10.1128/JVI.76.23.12335-12343.2002,PMC136916,,,"Attachment of Norwalk (NV), Snow Mountain (SMV), and Hawaii (HV) virus-like particles (VLPs) to specific ABH histo-blood group antigens was investigated by using human saliva and synthetic biotinylated carbohydrates. The three distinct Norwalk-like viruses (NLVs) have various capacities for binding ABH histo-blood group antigens, suggesting that different mechanisms for NLV attachment likely exist. Importantly, antisera from NV-infected human volunteers, as well as from mice inoculated with packaged Venezuelan equine encephalitis virus replicons expressing NV VLPs, blocked the ability of NV VLPs to bind synthetic H type 1, Le(b), and H type 3, suggesting a potential mechanism for antibody-mediated neutralization of NV.",,"['Harrington, Patrick R.', 'Lindesmith, Lisa', 'Yount, Boyd', 'Moe, Christine L.', 'Baric, Ralph S.']",,,,
,PMC,Receptor-Induced Conformational Changes of Murine Coronavirus Spike Protein,http://dx.doi.org/10.1128/JVI.76.23.11819-11826.2002,PMC136913,,,"Although murine coronavirus mouse hepatitis virus (MHV) enters cells by virus-cell membrane fusion triggered by its spike (S) protein, it is not well known how the S protein participates in fusion events. We reported that the soluble form of MHV receptor (soMHVR) transformed a nonfusogenic S protein into a fusogenic one (F. Taguchi and S. Matsuyama, J. Virol. 76:950-958, 2002). In the present study, we demonstrate that soMHVR induces the conformational changes of the S protein, as shown by the proteinase digestion test. A cl-2 mutant, srr7, of the MHV JHM virus (JHMV) was digested with proteinase K after treatment with soMHVR, and the resultant S protein was analyzed by Western blotting using monoclonal antibody (MAb) 10G, specific for the membrane-anchored S2 subunit. A 58-kDa fragment, encompassing the two heptad repeats in S2, was detected when srr7 was digested after soMHVR treatment, while no band was seen when the virus was untreated. The appearance of the proteinase-resistant fragment was dependent on the temperature and time of srr7 incubation with soMHVR and also on the concentration of soMHVR. Coimmunoprecipitation indicated that the direct binding of soMHVR to srr7 S protein induced these conformational changes; this was also suggested by the inhibition of the changes following pretreatment of soMHVR with anti-MHVR MAb CC1. soMHVR induced conformational changes of the S proteins of wild-type (wt) JHMV cl-2, as well as revertants from srr7, srr7A and srr7B; however, a major proportion of these S proteins were resistant to proteinase K even without soMHVR treatment. The implications of this proteinase-resistant fraction are discussed. This is the first report on receptor-induced conformational changes of the membrane-anchored fragment of the coronavirus S protein.",,"['Matsuyama, Shutoku', 'Taguchi, Fumihiro']",,,,
,PMC,Induction of Autoreactive CD8(+) Cytotoxic T Cells during Theiler's Murine Encephalomyelitis Virus Infection: Implications for Autoimmunity,http://dx.doi.org/10.1128/JVI.76.24.12834-12844.2002,PMC136689,,,"Theiler's murine encephalomyelitis virus (TMEV) belongs to the family Picornaviridae and causes demyelinating disease in the spinal cords of infected mice. Although immune responses have been shown to play an important role in demyelination, the precise effector mechanism(s) is unknown. Potentially autoreactive cytotoxic cells could contribute to the destruction. We tested whether an autoreactive cell induced by TMEV infection mediated cytotoxicity by using a 5-h (51)Cr release assay in SJL/J mice. Spleen cells from TMEV-infected mice were stimulated with irradiated TMEV antigen-presenting cells and used as effector cells. The effector cells differed from conventional cytotoxic T cells since these cells could kill both TMEV-infected and uninfected syngeneic or semisyngenic cell lines (PSJLSV and BxSF11gSV) but could not kill an allogeneic cell line (C57SV). The TMEV-induced autoreactive cells were also different from conventional natural killer (NK) cells or lymphokine-activated killer (LAK) cells, because they could kill neither NK cell-sensitive YAC-1 nor NK cell-resistant P815 and EL4 cells. Induction of autoreactive cells was not detected in vaccinia virus infection. The autoreactive killing required direct cell-to-cell contact and was mediated by a Fas-FasL pathway but not by a perforin pathway. The phenotype of the killer cells was CD3(+) CD4(−) CD8(+). Intracerebral inoculation of the effector cells into naive mice caused meningitis and perivascular cuffing not only in the brain parenchyma but also in the spinal cord, with no evidence of viral antigen-positive cells. This is the first report demonstrating that TMEV can induce autoreactive cytotoxic cells that induce central nervous system pathology.",,"['Tsunoda, Ikuo', 'Kuang, Li-Qing', 'Fujinami, Robert S.']",,,,
,PMC,Coronaviruses Maintain Viability despite Dramatic Rearrangements of the Strictly Conserved Genome Organization,http://dx.doi.org/10.1128/JVI.76.24.12491-12502.2002,PMC136672,,,"Despite their high frequency of RNA recombination, the plus-strand coronaviruses have a characteristic, strictly conserved genome organization with the essential genes occurring in the order 5′-polymerase (pol)-S-E-M-N-3′. We have investigated the significance of this remarkable conservation by rearrangement of the murine coronavirus genome through targeted recombination. Thus, viruses were prepared with the following gene order: 5′-pol-S-M-E-N-3′, 5′-pol-S-N-E-M-3′, 5′-pol-M-S-E-N-3′, and 5′-pol-E-M-S-N-3′. All of these viruses were surprisingly viable, and most viruses replicated in cell culture with growth characteristics similar to those of the parental virus. The recombinant virus with the gene order 5′-pol-E-M-S-N-3′ was also tested for the ability to replicate in the natural host, the mouse. The results indicate that the canonical coronavirus genome organization is not essential for replication in vitro and in vivo. Deliberate rearrangement of the viral genes may be useful in the generation of attenuated coronaviruses, which due to their reduced risk of generating viable viruses by recombination with circulating field viruses, would make safer vaccines.",,"['de Haan, Cornelis A. M.', 'Volders, Haukeline', 'Koetzner, Cheri A.', 'Masters, Paul S.', 'Rottier, Peter J. M.']",,,,
,PMC,"Detection of novel members, structure–function analysis and evolutionary classification of the 2H phosphoesterase superfamily",,PMC137960,,,"2′,3′ Cyclic nucleotide phosphodiesterases are enzymes that catalyze at least two distinct steps in the splicing of tRNA introns in eukaryotes. Recently, the biochemistry and structure of these enzymes, from yeast and the plant Arabidopsis thaliana, have been extensively studied. They were found to share a common active site, characterized by two conserved histidines, with the bacterial tRNA-ligating enzyme LigT and the vertebrate myelin-associated 2′,3′ phosphodiesterases. Using sensitive sequence profile analysis methods, we show that these enzymes define a large superfamily of predicted phosphoesterases with two conserved histidines (hence 2H phosphoesterase superfamily). We identify several new families of 2H phosphoesterases and present a complete evolutionary classification of this superfamily. We also carry out a structure– function analysis of these proteins and present evidence for diverse interactions for different families, within this superfamily, with RNA substrates and protein partners. In particular, we show that eukaryotes contain two ancient families of these proteins that might be involved in RNA processing, transcriptional co-activation and post-transcriptional gene silencing. Another eukaryotic family restricted to vertebrates and insects is combined with UBA and SH3 domains suggesting a role in signal transduction. We detect these phosphoesterase modules in polyproteins of certain retroviruses, rotaviruses and coronaviruses, where they could function in capping and processing of viral RNAs. Furthermore, we present evidence for multiple families of 2H phosphoesterases in bacteria, which might be involved in the processing of small molecules with the 2′,3′ cyclic phosphoester linkages. The evolutionary analysis suggests that the 2H domain emerged through a duplication of a simple structural unit containing a single catalytic histidine prior to the last common ancestor of all life forms. Initially, this domain appears to have been involved in RNA processing and it appears to have been recruited to perform various other functions in later stages of evolution.",,"['Mazumder, Raja', 'Iyer, Lakshminarayan M.', 'Vasudevan, Sona', 'Aravind, L.']",,,,
,PMC,Infection as a cause of multiple sclerosis : Theories abound because no one knows the answers yet,,PMC1124624,,,,,"Murray, Jock",,,,
,PMC,Microarray-based detection and genotyping of viral pathogens,http://dx.doi.org/10.1073/pnas.242579699,PMC137777,,,"The detection of viral pathogens is of critical importance in biology, medicine, and agriculture. Unfortunately, existing techniques to screen for a broad spectrum of viruses suffer from severe limitations. To facilitate the comprehensive and unbiased analysis of viral prevalence in a given biological setting, we have developed a genomic strategy for highly parallel viral screening. The cornerstone of this approach is a long oligonucleotide (70-mer) DNA microarray capable of simultaneously detecting hundreds of viruses. Using virally infected cell cultures, we were able to efficiently detect and identify many diverse viruses. Related viral serotypes could be distinguished by the unique pattern of hybridization generated by each virus. Furthermore, by selecting microarray elements derived from highly conserved regions within viral families, individual viruses that were not explicitly represented on the microarray were still detected, raising the possibility that this approach could be used for virus discovery. Finally, by using a random PCR amplification strategy in conjunction with the microarray, we were able to detect multiple viruses in human respiratory specimens without the use of sequence-specific or degenerate primers. This method is versatile and greatly expands the spectrum of detectable viruses in a single assay while simultaneously providing the capability to discriminate among viral subtypes.",,"['Wang, David', 'Coscoy, Laurent', 'Zylberberg, Maxine', 'Avila, Pedro C.', 'Boushey, Homer A.', 'Ganem, Don', 'DeRisi, Joseph L.']",,,,
,PMC,QUIZ CORNER,,PMC339747,,,,,,,,,
,PMC,In Vitro Detection of Apoptosis in Monocytes/Macrophages Infected with Human Coronavirus,http://dx.doi.org/10.1128/CDLI.9.6.1392-1395.2002,PMC130109,,,"Human coronavirus (HCoV) strain 229E infection, but not HCoV strain OC43 infection, of monocytes/macrophages from healthy donors and patients with multiple sclerosis in remission resulted in increased apoptosis, as measured by DNA changes and annexin V staining. Apoptosis correlated with the differential release of infectious virus. HCoV strain 229E titers were 10(3.5) to 10(6) 50% tissue culture-infective doses (TCID(50))/ml, and HCoV strain OC43 titers were only 10(1.2) to 10(2.7) TCID(50)/ml.",,"Collins, Arlene R.",,,,
,PMC,Nucleocapsid Protein-Based Enzyme-Linked Immunosorbent Assay for Detection and Differentiation of Antibodies against European and North American Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1128/CDLI.9.6.1183-1191.2002,PMC130101,,,"Two types of porcine reproductive and respiratory syndrome virus (PRRSV) have been reported, the European type (EU PRRSV) and the North American type (US PRRSV). We developed a dual enzyme-linked immunosorbent assay (ELISA) for the simultaneous detection and differentiation of serum antibodies directed against either of the two PRRSV types. This tandem PRRS ELISA is based on affinity-purified recombinant nucleocapsid protein expressed in Escherichia coli. Sensitivity and specificity were assessed by using the IDEXX HerdChek PRRS ELISA and the indirect immunofluorescence assay as reference tests. A total of 1,571 sera originating from the United States, Europe, and two PRRS-free countries, i.e., Switzerland and New Zealand, were used for validation of the tandem PRRS ELISA. The new test performed at least as well as the reference tests in regard to sensitivity (0.94 for the US PRRS ELISA and 0.93 for the EU PRRS ELISA) and specificity (0.96 for the US PRRS ELISA and 0.99 for the EU PRRS ELISA). Positive sera were correctly differentiated in 582 of 591 cases, indicating a high differentiation capability of this dual ELISA. The robustness and repeatability of the test were assessed and found to be appropriate for diagnostic applications. Taken together, the data indicate that the tandem PRRS ELISA described here is the first differentiation ELISA for PRRSV serology based on recombinant antigen. It is convenient with respect to antigen production, and it is reliable, economical, and highly sensitive and specific. Thus, it is considered to be a powerful tool for routine diagnostics, epidemiological surveys, and outbreak investigations.",,"['Seuberlich, Torsten', 'Tratschin, Jon-Duri', 'Thür, Barbara', 'Hofmann, Martin A.']",,,,
,PMC,The iddm4 Locus Segregates With Diabetes Susceptibility in Congenic WF.iddm4 Rats,,PMC4034451,,,"Viral antibody–free BBDR and WF rats never develop spontaneous diabetes. BBDR rats, however, develop autoimmune diabetes after perturbation of the immune system, e.g., by viral infection. We previously identified a disease-susceptibility locus in the BBDR rat, iddm4, which is associated with the development of autoimmune diabetes after treatment with polyinosinic:polycytidylic acid and an antibody that depletes ART2(+) regulatory cells. We have now developed lines of congenic WF.iddm4 rats and report that in an intercross of N5 generation WF.iddm4 rats, ∼70% of animals either homozygous or heterozygous for the BBDR origin allele of iddm4 became hyperglycemic after treatment to induce diabetes. Fewer than 20% of rats expressing the WF origin allele of iddm4 became diabetic. Testing the progeny of various recombinant N5 WF.iddm4 congenic rats for susceptibility to diabetes suggests that iddm4 is centered on a small segment of chromosome 4 bounded by the proximal marker D4Rat135 and the distal marker D4Got51, an interval of <2.8 cM. The allele at iddm4 has 79% sensitivity and 80% specificity in prediction of diabetes in rats that are segregating for this locus. These characteristics suggest that iddm4 is one of the most powerful non–major histocompatibility complex determinants of susceptibility to autoimmune diabetes described to date.",,"['Mordes, John P.', 'Leif, Jean', 'Novak, Stephen', 'DeScipio, Cheryl', 'Greiner, Dale L.', 'Blankenhorn, Elizabeth P.']",,,,
,PMC,"The Drosophila slamdance gene: a mutation in an aminopeptidase can cause seizure, paralysis and neuronal failure.",,PMC1462322,,,"We report here the characterization of slamdance (sda), a Drosophila melanogaster ""bang-sensitive"" (BS) paralytic mutant. This mutant exhibits hyperactive behavior and paralysis following a mechanical ""bang"" or electrical shock. Electrophysiological analyses have shown that this mutant is much more prone to seizure episodes than normal flies because it has a drastically lowered seizure threshold. Through genetic mapping, molecular cloning, and RNA interference, we have demonstrated that the sda phenotype can be attributed to a mutation in the Drosophila homolog of the human aminopeptidase N (APN) gene. Furthermore, using mRNA in situ hybridization and LacZ staining, we have found that the sda gene is expressed specifically in the central nervous system at particular developmental stages. Together, these results suggest that the bang sensitivity in sda mutants is caused by a defective APN gene that somehow increases seizure susceptibility. Finally, by using the sda mutation as a sensitized background, we have been able to identify a rich variety of sda enhancers and other independent BS mutations.",,"['Zhang, HaiGuang', 'Tan, Jeff', 'Reynolds, Elaine', 'Kuebler, Daniel', 'Faulhaber, Sally', 'Tanouye, Mark']",,,,
,PMC,Clinical Microbiology in the Year 2025,http://dx.doi.org/10.1128/JCM.40.11.3889-3893.2002,PMC139721,,,,,"['Dunne, Jr., W. Michael', 'Pinckard, J.Keith', 'Hooper, Lora V.']",,,,
,PMC,Virologic and Serologic Identification of Minute Virus of Canines (Canine Parvovirus Type 1) from Dogs in Japan,http://dx.doi.org/10.1128/JCM.40.11.3993-3998.2002,PMC139639,,,"Minute virus of canines (MVC), also known as canine parvovirus type 1, was initially believed to be a nonpathogenic agent, since it was first isolated from canine fecal specimens in the late 1960s. However, subsequent pathological as well as epidemiological studies suggested that MVC is a pathogen of neonatal puppies and is widely distributed among domestic dogs in the United States. The virus also has been shown to cause fetal deaths. Nevertheless, the virus was not detected in dogs outside the United States until recently, presumably because of a lack of widespread availability of the only susceptible canine cell line, WRCC/3873D, used for MVC isolation. We examined 470 clinical specimens from 346 dogs by PCR and detected MVC-specific gene fragments from four diseased puppies (positive rate, 1.2%). Viruses were recovered from three PCR-positive rectal specimens by using WRCC/3873D and MDCK cells. The isolates possessed antigenic and genomic properties similar to those of the U.S. reference strain GA3 and were identified as MVC. In addition, seroepidemiological evidence that 5.0% of dogs possessed anti-MVC antibodies also indicated the presence of MVC infection among dogs in Japan. From this study and several recent European reports describing MVC field cases, it is evident that MVC is distributed among domestic dogs worldwide.",,"['Mochizuki, Masami', 'Hashimoto, Michiru', 'Hajima, Takayuki', 'Takiguchi, Mitsuyoshi', 'Hashimoto, Akira', 'Une, Yumi', 'Roerink, Frank', 'Ohshima, Takahisa', 'Parrish, Colin R.', 'Carmichael, Leland E.']",,,,
,PMC,"Generation of a Replication-Competent, Propagation-Deficient Virus Vector Based on the Transmissible Gastroenteritis Coronavirus Genome",http://dx.doi.org/10.1128/JVI.76.22.11518-11529.2002,PMC136772,,,"Replication-competent propagation-deficient virus vectors based on the transmissible gastroenteritis coronavirus (TGEV) genome that are deficient in the essential E gene have been developed by complementation within E(+) packaging cell lines. Cell lines expressing the TGEV E protein were established using the noncytopathic Sindbis virus replicon pSINrep21. In addition, cell lines stably expressing the E gene under the CMV promoter have been developed. The Sindbis replicon vector and the ectopic TGEV E protein did not interfere with the rescue of infectious TGEV from full-length cDNA. Recombinant TGEV deficient in the nonessential 3a and 3b genes and the essential E gene (rTGEV-Δ3abΔE) was successfully rescued in these cell lines. rTGEV-Δ3abΔE reached high titers (10(7) PFU/ml) in baby hamster kidney cells expressing porcine aminopeptidase N (BHK-pAPN), the cellular receptor for TGEV, using Sindbis replicon and reached titers up to 5 × 10(5) PFU/ml in cells stably expressing E protein under the control of the CMV promoter. The virus titers were proportional to the E protein expression level. The rTGEV-Δ3abΔE virions produced in the packaging cell line showed the same morphology and stability under different pHs and temperatures as virus derived from the full-length rTGEV genome, although a delay in virus assembly was observed by electron microscopy and virus titration in the complementation system in relation to the wild-type virus. These viruses were stably grown for >10 passages in the E(+) packaging cell lines. The availability of packaging cell lines will significantly facilitate the production of safe TGEV-derived vectors for vaccination and possibly gene therapy.",,"['Ortego, Javier', 'Escors, David', 'Laude, Hubert', 'Enjuanes, Luis']",,,,
,PMC,Sialic Acid Functions in Enterovirus 70 Binding and Infection,http://dx.doi.org/10.1128/JVI.76.22.11265-11272.2002,PMC136758,,,"The interaction of viruses with host cell receptors is the initial step in viral infection and is an important determinant of virus host range, tissue tropism, and pathogenesis. The complement regulatory protein decay-accelerating factor (DAF/CD55) is an attachment receptor for enterovirus 70 (EV70), a member of the Picornaviridae, commonly associated with an eye infection in humans known as acute hemorrhagic conjunctivitis. In early work, the EV70 receptor on erythrocytes, responsible for its hemagglutinating activity, was shown to be sensitive to neuraminidase, implying an essential role for sialic acid in virus attachment. Here, we extend these results to show that cell surface sialic acid is required for EV70 binding to nucleated cells susceptible to virus infection and that sialic acid binding is important in productive infection. Through the use of site-directed mutagenesis to eliminate the single N-linked glycosylation site of DAF and of a chimeric receptor protein in which the O-glycosylated domain of DAF was replaced by a region of the HLA-B44 molecule, a role in EV70 binding for the sialic acid residues of DAF was excluded, suggesting the existence of at least one additional, sialylated EV70-binding factor at the cell surface. Treatment of cells with metabolic inhibitors of glycosylation excluded a role for the N-linked oligosaccharides of glycoproteins but suggested that O-linked glycosylation is important for EV70 binding.",,"['Alexander, David A.', 'Dimock, Kenneth']",,,,
,PMC,Immunization of Macaques with Formalin-Inactivated Respiratory Syncytial Virus (RSV) Induces Interleukin-13-Associated Hypersensitivity to Subsequent RSV Infection,http://dx.doi.org/10.1128/JVI.76.22.11561-11569.2002,PMC136757,,,"Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and the elderly. RSV vaccine development has been hampered by results of clinical trials in the 1960s, when formalin-inactivated whole-RSV preparations adjuvated with alum (FI-RSV) were found to predispose infants for enhanced disease following subsequent natural RSV infection. We have reproduced this apparently immunopathological phenomenon in infant cynomolgus macaques and identified immunological and pathological correlates. Vaccination with FI-RSV induced specific virus-neutralizing antibody responses accompanied by strong lymphoproliferative responses. The vaccine-induced RSV-specific T cells predominantly produced the Th2 cytokines interleukin-13 (IL-13) and IL-5. Intratracheal challenge with a macaque-adapted wild-type RSV 3 months after the third vaccination elicited a hypersensitivity response associated with lung eosinophilia. The challenge resulted in a rapid boosting of IL-13-producing T cells in the FI-RSV-vaccinated animals but not in the FI-measles virus-vaccinated control animals. Two out of seven FI-RSV-vaccinated animals died 12 days after RSV challenge with pulmonary hyperinflation. Surprisingly, the lungs of these two animals did not show overt inflammatory lesions. However, upon vaccination the animals had shown the strongest lymphoproliferative responses associated with the most pronounced Th2 phenotype within their group. We hypothesize that an IL-13-associated asthma-like mechanism resulted in airway hyperreactivity in these animals. This nonhuman primate model will be an important tool to assess the safety of nonreplicating candidate RSV vaccines.",,"['de Swart, Rik L.', 'Kuiken, Thijs', 'Timmerman, Helga H.', 'Amerongen, Geert van', 'van den Hoogen, Bernadette G.', 'Vos, Helma W.', 'Neijens, Herman J.', 'Andeweg, Arno C.', 'Osterhaus, Albert D. M. E.']",,,,
,PMC,The Transmembrane Domain and Cytoplasmic Tail of Herpes Simplex Virus Type 1 Glycoprotein H Play a Role in Membrane Fusion,http://dx.doi.org/10.1128/JVI.76.21.10708-10716.2002,PMC136627,,,"Herpes simplex virus glycoprotein H (gH) is one of the four virion envelope proteins which are required for virus entry and for cell-cell fusion in a transient system. In this report, the role of the transmembrane and cytoplasmic tail domains of gH in membrane fusion was investigated by generating chimeric constructs in which these regions were replaced with analogous domains from other molecules and by introducing amino acid substitutions within the membrane-spanning sequence. gH molecules which lack the authentic transmembrane domain or cytoplasmic tail were unable to mediate cell-cell fusion when coexpressed with gB, gD, and gL and were unable to rescue the infectivity of a gH-null virus as efficiently as a wild-type gH molecule. Many amino acid substitutions of specific amino acid residues within the transmembrane domain also affected cell-cell fusion, in particular, those introduced at a conserved glycine residue. Some gH mutants that were impaired in cell-cell fusion were nevertheless able to rescue the infectivity of a gH-negative virus, but these pseudotyped virions entered cells more slowly than wild-type virions. These results indicate that the fusion event mediated by the coexpression of gHL, gB, and gD in cells shares common features with the fusion of the virus envelope with the plasma membrane, they point to a likely role for the membrane-spanning and cytoplasmic tail domains of gH in both processes, and they suggest that a conserved glycine residue in the membrane-spanning sequence is crucial for efficient fusion.",,"['Harman, Andrew', 'Browne, Helena', 'Minson, Tony']",,,,
,PMC,Mutations Conferring Resistance to Neutralization by a Soluble Form of the Neurotrophin Receptor (p75NTR) Map outside of the Known Antigenic Sites of the Rabies Virus Glycoprotein,http://dx.doi.org/10.1128/JVI.76.21.10756-10765.2002,PMC136618,,,"The neurotrophin receptor (p75NTR) serves as a receptor for rabies virus (RV). We expressed and purified a soluble chimera consisting of the p75NTR ectodomain fused to the human immunoglobulin G1 (IgG1) Fc fragment (p75-Fc). Although p75-Fc interacts with RV, the infectivity of RV did not decrease significantly when it was incubated in the presence of the soluble receptor alone. However, when it was subsequently incubated with an antihuman IgG directed against the Fc fragment of p75-Fc, the infectivity of RV was significantly lowered (>90%), whereas incubation with antihuman IgG alone had no effect. We then selected eight independent RV mutants that were not neutralized by p75-Fc and antihuman IgG (srr [soluble receptor resistant] mutants). Each mutant carried a single mutation in the glycoprotein gene leading to one amino acid substitution in the protein. A total of four different substitutions were found. Two of the mutations were located at position 318 (phenylalanine replaced by a serine or a valine residue), and two were located at position 352 (histidine replaced by a tyrosine or an arginine residue). All of the mutations prevented the interaction with p75NTR as either a soluble or a membrane-anchored form. Two mutants (F318S) and (H352R) resulted in the formation of small plaques on BSR cells, probably due to the slower maturation of the glycoprotein. Immunoprecipitation, immunofluorescence, and neutralization assays showed that the four mutated glycoproteins still interacted with representative anti-RV glycoprotein monoclonal antibodies (MAbs), indicating that p75NTR binds outside of the known RV glycoprotein antigenic sites.",,"['Langevin, Christelle', 'Tuffereau, Christine']",,,,
,PMC,"Characterization of Two New Structural Glycoproteins, GP(3) and GP(4), of Equine Arteritis Virus",http://dx.doi.org/10.1128/JVI.76.21.10829-10840.2002,PMC136612,,,"Equine arteritis virus (EAV) is an enveloped, positive-stranded RNA virus belonging to the family Arteriviridae of the order Nidovirales. Four envelope proteins have hitherto been identified in EAV particles: the predominant membrane proteins M and G(L), the unglycosylated small envelope protein E, and the nonabundant membrane glycoprotein G(S). In this study, we established that the products of EAV open reading frame 3 (ORF3) and ORF4 (designated GP(3) and GP(4), respectively) are also minor structural glycoproteins. The proteins were first characterized by various analyses after in vitro translation of RNA transcripts in a rabbit reticulocyte lysate in the presence and absence of microsomal membranes. We subsequently expressed ORF3 and -4 in baby hamster kidney cells by using the vaccinia virus expression system and, finally, analyzed the GP(3) and GP(4) proteins synthesized in EAV-infected cells. The results showed that GP(4) is a class I integral membrane protein of 28 kDa with three functional N-glycosylation sites and with little, if any, of its carboxy terminus exposed. Both after independent expression and in EAV-infected cells, the protein localizes in the endoplasmic reticulum (ER), as demonstrated biochemically by analysis of its oligosaccharide side chains and as visualized directly by immunofluorescence studies. GP(3), on the other hand, is a heavily glycosylated protein whose hydrophobic amino terminus is not cleaved off. It is an integral membrane protein anchored by either or both of its hydrophobic terminal domains and with no parts detectably exposed cytoplasmically. Also, GP(3) localizes in the ER when expressed independently and in the context of an EAV infection. Only a small fraction of the GP(3) and GP(4) proteins synthesized in infected cells ends up in virions. Most, but not all, of the oligosaccharides of these virion glycoproteins are biochemically mature. Our results bring the number of EAV envelope proteins to six.",,"['Wieringa, Roeland', 'de Vries, Antoine A. F.', 'Raamsman, Martin J. B.', 'Rottier, Peter J. M.']",,,,
,PMC,Systematic Assembly of a Full-Length Infectious cDNA of Mouse Hepatitis Virus Strain A59,http://dx.doi.org/10.1128/JVI.76.21.11065-11078.2002,PMC136593,,,"A novel method was developed to assemble a full-length infectious cDNA of the group II coronavirus mouse hepatitis virus strain A59 (MHV-A59). Seven contiguous cDNA clones that spanned the 31.5-kb MHV genome were isolated. The ends of the cDNAs were engineered with unique junctions and assembled with only the adjacent cDNA subclones, resulting in an intact MHV-A59 cDNA construct of ∼31.5 kb in length. The interconnecting restriction site junctions that are located at the ends of each cDNA are systematically removed during the assembly of the complete full-length cDNA product, allowing reassembly without the introduction of nucleotide changes. RNA transcripts derived from the full-length MHV-A59 construct were infectious, although transfection frequencies were enhanced 10- to 15-fold in the presence of transcripts encoding the nucleocapsid protein N. Plaque-purified virus derived from the infectious construct replicated efficiently and displayed similar growth kinetics, plaque morphology, and cytopathology in murine cells as did wild-type MHV-A59. Molecularly cloned viruses recognized the MHV receptor (MHVR) for docking and entry, and pretreatment of cells with monoclonal antibodies against MHVR blocked virus entry and replication. Cells infected with molecularly cloned MHV-A59 virus expressed replicase (gene 1) proteins identical to those of laboratory MHV-A59. Importantly, the molecularly cloned viruses contained three marker mutations that had been derived from the engineered component clones. Full-length infectious constructs of MHV-A59 will permit genetic modifications of the entire coronavirus genome, particularly in the replicase gene. The method has the potential to be used to construct viral, microbial, or eukaryotic genomes approaching several million base pairs in length and used to insert restriction sites at any given nucleotide in a microbial genome.",,"['Yount, Boyd', 'Denison, Mark R.', 'Weiss, Susan R.', 'Baric, Ralph S.']",,,,
,PMC,Preparation of human single chain Fv antibody against hepatitis C virus E2 protein and its identification in immunohistochemistry,http://dx.doi.org/10.3748/wjg.v8.i5.863,PMC4656576,,,"AIM: To screen human single chain Fv antibody (scFv) against hepatitis C virus E2 antigen and identify its application in immunohistochemistry. METHODS: The phage antibody library was panned by HCV E2 antigen, which was coated in microtiter plate. After five rounds of biopanning, 56 phage clones were identified specific to HCV E2 antigen. The selected scFv clones were digested by Sfi I/Not I and DNA was sequenced. Then it was subcloned into the vector pCANTAB5E for expression as E-tagged soluble scFv. The liver tissue sections from normal person and patients with chronic hepatitis B and chronic hepatitis C were immunostained with HCV E2 scFv antibody. RESULTS: The data of scFv-E2 DNA digestion and DNA sequencing showed that the scFv gene is composed of 750 bp. ELISA and immunohistochemistry demonstrated that the human single chain Fv antibody against hepatitis C E2 antigen has a specific binding character with hepatitis virus E2 antigen and paraffin-embedded tissue, but did not react with liver tissues from healthy persons or patients with chronic hepatitis B. CONCLUSION: We have successfully screened and identified HCV E2 scFv and the scFv could be used in the immunostaining of liver tissue sections from patients with chronic hepatitis C.",,"['Zhong, Yan-Wei', 'Cheng, Jun', 'Wang, Gang', 'Shi, Shuang-Shuang', 'Li, Li', 'Zhang, Ling-Xia', 'Chen, Ju-Mei']",,,,
,PMC,A nucleolar TAR decoy inhibitor of HIV-1 replication,http://dx.doi.org/10.1073/pnas.212229599,PMC137834,,,"Tat is a critical regulatory factor in HIV-1 gene expression. It mediates the transactivation of transcription from the HIV-1 LTR by binding to the transactivation response (TAR) element in a complex with cyclin T1. Because of its critical and early role in HIV gene expression, Tat and its interaction with the TAR element constitute important therapeutic targets for the treatment of HIV-1 infection. Based on the known nucleolar localization properties of Tat, we constructed a chimeric small nucleolar RNA-TAR decoy that localizes to the nucleoli of human cells and colocalizes in the nucleolus with a Tat-enhanced GFP fusion protein. When the chimeric RNA was stably expressed in human T lymphoblastoid CEM cells it potently inhibited HIV-1 replication. These results demonstrate that the nucleolar trafficking of Tat is critical for HIV-1 replication and suggests a role for the nucleolus in HIV-1 viral replication.",,"['Michienzi, Alessandro', 'Li, Shirley', 'Zaia, John A.', 'Rossi, John J.']",,,,
,PMC,Virus-Induced Demyelination in Nude Mice Is Mediated by γδ T Cells,,PMC1867296,,,"Infection of mice with mouse hepatitis virus (MHV), strain JHM, results in acute and chronic demyelination with many similarities to the human disease multiple sclerosis. This pathological process is primarily T cell-mediated and MHV infection of mice lacking B and T cells does not result in demyelination. In apparent contradiction to these results, robust demyelination is detected in MHV-infected young nude (athymic) mice. Herein, we show that demyelination in nude mice was mediated by γδ T cells. These cells, but not conventional CD4 or CD8 αβ T cells, were detected in the central nervous system of MHV-infected nude mice and their depletion with neutralizing antibody resulted in an 80% reduction in demyelination. These results show, for the first time, that γδ T cells can substitute for αβ T cells in a virus model of demyelination and further support a pathological role for γδ T cells in patients with multiple sclerosis.",,"['Dandekar, Ajai A.', 'Perlman, Stanley']",,,,
,PMC,Field study of bovine coronavirus vaccine enriched with hemagglutinating antigen for winter dysentery in dairy cows,,PMC227016,,,"A field study of a vaccine; prepared by solubilizing cells infected with bovine coronavirus, Triton X-100, and mixing with an oil adjuvant, was performed at 9 farms over 4 prefectures. The cattle tested were Holstein dairy cows aged 2 to 10 years. A vaccination group consisted of 157 animals (including 132 pregnant cows) and a non-vaccinated control group consisted of 50 animals. The cows received 2 intramuscular injections of vaccine (2 mL) at 3-week intervals. Vaccinated cows did not develop abnormalities, such as a decrease in milk production volume, and all pregnant animals calved normally. The geometric mean of the hemagglutination inhibition antibody titer was 34.2 before vaccination in test cows. The titer had increased to 105.6, 3 weeks after the 1st injection and peaked at 755.6, 1 month after the 2nd injection. A high antibody titer persisted at 396.0; 241.0; and 201.5, at 3, 6, and 9 months after the 2nd injection, respectively. This confirms the safety and high antibody-response induced by this prototype vaccine. Therefore, this vaccine may be useful for the prevention of winter dysentery caused by bovine coronavirus infection.",,"['Takamura, Keizo', 'Matsumoto, Yuichi', 'Shimizu, Yukio']",,,,
,PMC,Absence of Fibroblast Growth Factor 2 Promotes Oligodendroglial Repopulation of Demyelinated White Matter,http://dx.doi.org/10.1523/JNEUROSCI.22-19-08574.2002,PMC6757804,,,"This study takes advantage of fibroblast growth factor 2 (FGF2) knock-out mice to determine the contribution of FGF2 to the regeneration of oligodendrocytes in the adult CNS. The role of FGF2 during spontaneous remyelination was examined using two complementary mouse models of experimental demyelination. The murine hepatitis virus strain A59 (MHV-A59) model produces focal areas of spinal cord demyelination with inflammation. The cuprizone neurotoxicant model causes extensive corpus callosum demyelination without a lymphocytic cell response. In both models, FGF2 expression is upregulated in areas of demyelination in wild-type mice. Surprisingly, in both models, oligodendrocyte repopulation of demyelinated white matter was significantly increased in FGF2 −/− mice compared with wild-type mice and even surpassed the oligodendrocyte density of nonlesioned mice. This dramatic result indicated that the absence of FGF2 promoted oligodendrocyte regeneration, possibly by enhancing oligodendrocyte progenitor proliferation and/or differentiation. FGF2 −/− and +/+ mice had similar oligodendrocyte progenitor densities in normal adult CNS, as well as similar progenitor proliferation and accumulation during demyelination. To directly analyze progenitor differentiation, glial cultures from spinal cords of wild-type mice undergoing remyelination after MHV-A59 demyelination were treated for 3 d with either exogenous FGF2 or an FGF2 neutralizing antibody. Elevating FGF2 favored progenitor proliferation, whereas attenuating endogenous FGF2 activity promoted the differentiation of progenitors into oligodendrocytes. Thesein vitro results are consistent with enhanced progenitor differentiation in FGF2 −/− mice. These studies demonstrate that the FGF2 genotype regulates oligodendrocyte regeneration and that FGF2 appears to inhibit oligodendrocyte lineage differentiation during remyelination.",,"['Armstrong, Regina C.', 'Le, Tuan Q.', 'Frost, Emma E.', 'Borke, Rosemary C.', 'Vana, Adam C.']",,,,
,PMC,Phosphorylation of the Porcine Reproductive and Respiratory Syndrome Virus Nucleocapsid Protein,http://dx.doi.org/10.1128/JVI.76.20.10569-10576.2002,PMC136587,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) is a cytoplasmic RNA virus with the unique or unusual feature of having a nucleocapsid (N) protein that is specifically transported to the nucleolus of virus-infected cells. In this communication, we show that the N protein is a phosphoprotein. Phosphoamino acid analysis of authentic and recombinant N proteins demonstrated that serine residues were exclusively phosphorylated. The pattern of phosphorylated N protein cellular distribution in comparison with that of [(35)S]methionine-labeled N protein suggested that phosphorylation does not influence subcellular localization of the protein. Time course studies showed that phosphorylation occurred during, or shortly after, synthesis of the N protein and that the protein remained stably phosphorylated throughout the life cycle of the virus to the extent that phosphorylated N protein was found in the mature virion. Two-dimensional electrophoresis and acid-urea gel electrophoresis showed that one species of the N protein is predominant in virus-infected cells, suggesting that multiple phosphorylated isoforms of N do not exist.",,"['Wootton, Sarah K.', 'Rowland, Raymond R. R.', 'Yoo, Dongwan']",,,,
,PMC,Newcastle Disease Virus (NDV) Marker Vaccine: an Immunodominant Epitope on the Nucleoprotein Gene of NDV Can Be Deleted or Replaced by a Foreign Epitope,http://dx.doi.org/10.1128/JVI.76.20.10138-10146.2002,PMC136582,,,"The nucleoprotein (NP) of Newcastle disease virus (NDV) functions primarily to encapsidate the virus genome for the purpose of RNA transcription, replication, and packaging. This conserved multifunctional protein is also efficient in inducing NDV-specific antibody in chickens. Here, we localized a conserved B-cell immunodominant epitope (IDE) spanning residues 447 to 455 and successfully generated a recombinant NDV lacking the IDE by reverse genetics. Despite deletion of NP residues 443 to 460 encompassing the NP-IDE, the mutant NDV propagated in embryonated specific-pathogen-free chicken eggs to a level comparable to that of the parent virus. In addition, a B-cell epitope of the S2 glycoprotein of murine hepatitis virus (MHV) was inserted in-frame to replace the NP-IDE. Recombinant viruses properly expressing the introduced MHV epitope were successfully generated, demonstrating that the NP-IDE not only is dispensable for virus replication but also can be replaced by foreign sequences. Chickens immunized with the hybrid recombinants produced specific antibodies against the S2 glycoprotein of MHV and completely lacked antibodies directed against the NP-IDE. These marked-NDV recombinants, in conjunction with a diagnostic test, enable serological differentiation of vaccinated animals from infected animals and may be useful tools in ND eradication programs. The identification of a mutation-permissive region on the NP gene allows a rational approach to the insertion of protective epitopes and may be relevant for the design of NDV-based cross-protective marker vaccines.",,"['Mebatsion, Teshome', 'Koolen, Marck J. M.', 'de Vaan, Leonie T. C.', 'de Haas, Niels', 'Braber, Marian', 'Römer-Oberdörfer, Angela', 'van den Elzen, Paul', 'van der Marel, Pieter']",,,,
,PMC,Characterization of an Enteropathogenic Bovine Calicivirus Representing a Potentially New Calicivirus Genus,http://dx.doi.org/10.1128/JVI.76.20.10089-10098.2002,PMC136553,,,"Bovine enteric caliciviruses (BEC) are associated with diarrhea in young calves. The BEC strains detected in Europe form a third genogroup within the genus “Norwalk-like viruses” (NLV) of the family Caliciviridae. In this report, we present sequence, clinical, and histological data characterizing a novel enteropathogenic BEC strain, NB, detected in fecal specimens from calves in the United States. The complete RNA genome of the NB virus is 7,453 bases long and is organized into two open reading frames (ORFs). ORF-1 is 2,210 amino acids long and encodes a large nonstructural polyprotein contiguous with the major capsid protein (VP1), similar to the lagoviruses and “Sapporo-like viruses” (SLV). The conserved calicivirus motifs were identified in the nonstructural proteins. ORF-2 is located at the 3′ end of the genome and encodes a small basic protein (VP2) of 225 amino acids. The 5′ and 3′ untranslated regions are 74 and 67 bases long, respectively. Among caliciviruses, NB virus shows amino acid identities of 14.1 to 22.6% over the entire ORF-1 nonstructural-protein sequence with NLV, SLV, vesivirus, and lagovirus strains, while the overall sequence identity of the complete NB VP-1 with other caliciviruses is low, varying between 14.6 and 26.7%. Phylogenetic analysis of the complete VP1 protein, including strains from all four calicivirus genera, showed the closest grouping of NB virus to be with viruses in the genus Lagovirus, which cause liver infections and systemic hemorrhage in rabbits. In gnotobiotic calves, however, NB virus elicited only diarrhea and intestinal lesions that were most severe in the upper small intestine (duodenum and jejunum), similar to the NLV BEC strains. The tissues of major organs, including the lung, liver, kidney, and spleen, had no visible microscopic lesions.",,"['Smiley, J. R.', 'Chang, K. O.', 'Hayes, J.', 'Vinjé, J.', 'Saif, L. J.']",,,,
,PMC,Antibody Responses of Cattle with Respiratory Coronavirus Infections during Pathogenesis of Shipping Fever Pneumonia Are Lower with Antigens of Enteric Strains than with Those of a Respiratory Strain,http://dx.doi.org/10.1128/CDLI.9.5.1010-1013.2002,PMC120065,,,"The serum antibody responses of cattle with respiratory coronavirus infections during the pathogenesis of shipping fever pneumonia were analyzed with different bovine coronavirus antigens, including those from a wild-type respiratory bovine coronavirus (RBCV) strain (97TXSF-Lu 15-2) directly isolated from lung tissue from a fatally infected bovine, a wild-type enteropathogenic bovine coronavirus (EBCV) strain (Ly 138-3), and the highly cell culture-adapted, enteric prototype strain (EBCV L9-81). Infectivity-neutralizing (IN) and hemagglutinin-inhibiting (HAI) activities were tested. Sequential serum samples, collected during the onset of the respiratory coronavirus infection and at weekly intervals for 5 weeks thereafter, had significantly higher IN and HAI titers for antigens of RBCV strain 97TXSF-Lu15-2 than for the wild-type and the highly cell culture-adapted EBCV strains, with P values ranging from <0.0001 to 0.0483. The IN and HAI antibody responses against the two EBCV strains did not differ significantly, but the lowest titers were detected with EBCV strain L9-81.",,"['Lin, Xiao-Qing', ""O'Reilly, Kathy L."", 'Storz, Johannes']",,,,
,PMC,Molecular Characterization Confirms the Presence of a Divergent Strain of Canine Coronavirus (UWSMN-1) in Australia,http://dx.doi.org/10.1128/JCM.40.9.3518-3522.2002,PMC130832,,,"Canine coronavirus (CCV) UWSMN-1 was originally identified from an outbreak of fatal gastroenteritis in breeding colonies. In this report, we examined whether UWSMN-1 represents a novel divergent strain or is the result of recombination events between canine and feline coronavirus strains. Sequencing of various regions of the spike and polymerase genes confirms that UWSMN-1 is widely divergent from other CCV and feline coronavirus strains. These data raise the possibility that this strain is the first member of a novel third subtype of CCV.",,"['Naylor, Matthew J.', 'Walia, Charanjiv S.', 'McOrist, Steven', 'Lehrbach, Philip R.', 'Deane, Elizabeth M.', 'Harrison, Gavan A.']",,,,
,PMC,Laboratory Diagnosis of Lower Respiratory Tract Infections: Controversy and Conundrums,http://dx.doi.org/10.1128/JCM.40.9.3115-3120.2002,PMC130746,,,,,"Carroll, Karen C.",,,,
,PMC,Inhibition of Nuclear Import and Alteration of Nuclear Pore Complex Composition by Rhinovirus,http://dx.doi.org/10.1128/JVI.76.17.8787-8796.2002,PMC136411,,,"Nucleocytoplasmic trafficking pathways and the status of nuclear pore complex (NPC) components were examined in cells infected with rhinovirus type 14. A variety of shuttling and nonshuttling nuclear proteins, using multiple nuclear import pathways, accumulated in the cytoplasm of cells infected with rhinovirus. An in vitro nuclear import assay with semipermeabilized infected cells confirmed that nuclear import was inhibited and that docking of nuclear import receptor-cargo complexes at the cytoplasmic face of the NPC was prevented in rhinovirus-infected cells. The relocation of cellular proteins and inhibition of nuclear import correlated with the degradation of two NPC components, Nup153 and p62. The degradation of Nup153 and p62 was not due to induction of apoptosis, because p62 was not proteolyzed in apoptotic HeLa cells, and Nup153 was cleaved to produce a 130-kDa cleavage product that was not observed in cells infected with poliovirus or rhinovirus. The finding that both poliovirus and rhinovirus cause inhibition of nuclear import and degradation of NPC components suggests that this may be a common feature of the replicative cycle of picornaviruses. Inhibition of nuclear import is predicted to result in the cytoplasmic accumulation of a large number of nuclear proteins that could have functions in viral translation, RNA synthesis, packaging, or assembly. Additionally, inhibition of nuclear import also presents a novel strategy whereby cytoplasmic RNA viruses can evade host immune defenses by preventing signal transduction into the nucleus.",,"['Gustin, Kurt E.', 'Sarnow, Peter']",,,,
,PMC,Human Immunodeficiency Virus Type 1 (HIV-1) Tat Induces Nitric-oxide Synthase in Human Astroglia,http://dx.doi.org/10.1074/jbc.M205107200,PMC2041896,,,"Human immunodeficiency virus type 1 (HIV-1) infection is known to cause neuronal injury and dementia in a significant proportion of patients. However, the mechanism by which HIV-1 mediates its deleterious effects in the brain is poorly defined. The present study was undertaken to investigate the effect of the HIV-1 tat gene on the expression of inducible nitric-oxide synthase (iNOS) in human U373MG astroglial cells and primary astroglia. Expression of the tat gene as RSV-tat but not that of the CAT gene as RSV-CAT in U373MG astroglial cells led to the induction of NO production and the expression of iNOS protein and mRNA. Induction of NO production by recombinant HIV-1 Tat protein and inhibition of RSV-tat-induced NO production by anti-Tat antibodies suggest that RSV-tat-induced production of NO is dependent on Tat and that Tat is secreted from RSV-tat-transfected astroglia. Similar to U373MG astroglial cells, RSV-tat also induced the production of NO in human primary astroglia. The induction of human iNOS promoter-derived luciferase activity by the expression of RSV-tat suggests that RSV-tat induces the transcription of iNOS. To understand the mechanism of induction of iNOS, we investigated the role of NF-κB and C/EBPβ, transcription factors responsible for the induction of iNOS. Activation of NF-κB as well as C/EBPβ by RSV-tat, stimulation of RSV-tat-induced production of NO by the wild type of p65 and C/EBPβ, and inhibition of RSV-tat-induced production of NO by Δp65, a dominant-negative mutant of p65, and ΔC/EBPβ, a dominant-negative mutant of C/EBPβ, suggest that RSV-tat induces iNOS through the activation of NF-κB and C/EBPβ. In addition, we show that extracellular signal-regulated kinase (ERK) but not that p38 mitogen-activated protein kinase (MAPK) is involved in RSV-tat induced production of NO. Interestingly, PD98059, an inhibitor of the ERK pathway, and ΔERK2, a dominant-negative mutant of ERK2, inhibited RSV-tat-induced production of NO through the inhibition of C/EBPβ but not that of NF-κB. This study illustrates a novel role for HIV-1 tat in inducing the expression of iNOS in human astrocytes that may participate in the pathogenesis of HIV-associated dementia.",,"['Liu, Xiaojuan', 'Jana, Malabendu', 'Dasgupta, Subhajit', 'Koka, Sreenivas', 'He, Jun', 'Wood, Charles', 'Pahan, Kalipada']",,,,
,PMC,A long-term study on the prevalence of shiga toxin-producing Escherichia coli (STEC) on four German cattle farms.,,PMC2869863,,,"The occurrence of Shiga toxin-producing Escherichia coli (STEC) was studied on four cattle farms. STEC were detected in 29-82% of the cattle. STEC with additional EHEC markers were detected on all farms. The occurrence of the complete virulence marker pattern (stx1 and/or stx2, eae, EHEC(hlyA), katP, espP) was correlated with the presence of known STEC serotypes. STEC O26:H11 and O165:H25 with the complete pattern of virulence markers were the most prevalent. STEC O157 (H7/H-) STEC O103:H2 and STEC O145:H- were found sporadically. Five clonal subgroups of the STEC O26:H11 isolates were identified by pulsed-field gel electrophoresis. STEC O26:H11 were present in three groups of cattle. This serotype was detected in a single group over the entire fattening period. Most STEC O26:H11 with the complete pattern of potential virulence markers were found in clinically healthy cattle. These animals may represent a risk factor for farmers and consumers.",,"['Geue, L.', 'Segura-Alvarez, M.', 'Conraths, F. J.', 'Kuczius, T.', 'Bockemühl, J.', 'Karch, H.', 'Gallien, P.']",,,,
,PMC,Matrix Metalloproteinase Expression Correlates with Virulence following Neurotropic Mouse Hepatitis Virus Infection,http://dx.doi.org/10.1128/JVI.76.15.7374-7384.2002,PMC136378,,,"The relationship(s) between viral virulence and matrix metalloproteinase (MMP) expression in the central nervous system (CNS) of mice undergoing lethal and sublethal infections with neurotropic mouse hepatitis virus was investigated. Lethal infection induced increased levels of MMP-3 and MMP-12 mRNAs as well as that of tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) compared to sublethal infection. Increased induction of MMP, TIMP, and chemokine expression correlated with increased virus replication but not with inflammatory cell infiltration. Infection of immunosuppressed mice suggested that expression of most MMP, TIMP, and chemokine mRNA was induced primarily in CNS-resident cells. By contrast, MMP-9 protein activity was associated with the infiltration of neutrophils into the CNS. These data indicate an association between the magnitude of inflammatory gene expression within the CNS and viral virulence.",,"['Zhou, Jiehao', 'Stohlman, Stephen A.', 'Atkinson, Roscoe', 'Hinton, David R.', 'Marten, Norman W.']",,,,
,PMC,Comparative studies of frameshifting and nonframeshifting RNA pseudoknots: a mutational and NMR investigation of pseudoknots derived from the bacteriophage T2 gene 32 mRNA and the retroviral gag-pro frameshift site.,,PMC1370320,,,"Mutational and NMR methods were used to investigate features of sequence, structure, and dynamics that are associated with the ability of a pseudoknot to stimulate a -1 frameshift. In vitro frameshift assays were performed on retroviral gag-pro frameshift-stimulating pseudoknots and their derivatives, a pseudoknot from the gene 32 mRNA of bacteriophage T2 that is not naturally associated with frameshifting, and hybrids of these pseudoknots. Results show that the gag-pro pseudoknot from human endogenous retrovirus-K10 (HERV) stimulates a -1 frameshift with an efficiency similar to that of the closely related retrovirus MMTV. The bacteriophage T2 mRNA pseudoknot was found to be a poor stimulator of frameshifting, supporting a hypothesis that the retroviral pseudoknots have distinctive properties that make them efficient frameshift stimulators. A hybrid, designed by combining features of the bacteriophage and retroviral pseudoknots, was found to stimulate frameshifting while retaining significant structural similarity to the nonframeshifting bacteriophage pseudoknot. Mutational analyses of the retroviral and hybrid pseudoknots were used to evaluate the effects of an unpaired (wedged) adenosine at the junction of the pseudoknot stems, changing the base pairs near the junction of the two stems, and changing the identity of the loop 2 nucleotide nearest the junction of the stems. Pseudoknots both with and without the wedged adenosine can stimulate frameshifting, though the identities of the nucleotides near the stem1/stem2 junction do influence efficiency. NMR data showed that the bacteriophage and hybrid pseudoknots are similar in their local structure at the junction of the stems, indicating that pseudoknots that are similar in this structural feature can differ radically in their ability to stimulate frameshifting. NMR methods were used to compare the internal motions of the bacteriophage T2 pseudoknot and representative frameshifting pseudoknots. The stems of the investigated pseudoknots are similarly well ordered on the time scales to which nitrogen-15 relaxation data are sensitive; however, solvent exchange rates for protons at the junction of the two stems of the nonframeshifting bacteriophage pseudoknot are significantly slower than the analogous protons in the representative frameshifting pseudoknots.",,"['Wang, Yue', 'Wills, Norma M', 'Du, Zhihua', 'Rangan, Anupama', 'Atkins, John F', 'Gesteland, Raymond F', 'Hoffman, David W']",,,,
,PMC,Physiology and behavior of dogs during air transport,,PMC227007,,,"Twenty-four beagles were used to measure physiological and behavioral reactions to air transport. Each of 3 groups of 4 sedated (with 0.5 mg/kg body weight of acepromazine maleate) and 4 non-sedated (control) dogs was flown on a separate flight between Montreal, Quebec, and Toronto, Ontario, after being transported by road from Quebec City to Montreal. Saliva and blood samples were taken before ground and air transport and after air transport. The heart rate was monitored during the whole experiment except during ground transport, and behavior was monitored by video during air transport. Sedation did not affect any of the variables measured. The mean plasma cortisol concentration was significantly higher (P < 0.05) after ground transport than at baseline (225.3 vs 134.5 nmol/L); the mean salivary cortisol concentration was significantly higher (P < 0.05) after both ground and air transport than at baseline (16.2 and 14.8, respectively, vs 12.6 nmol/L). The mean neutrophil count was significantly higher (P < 0.05) after both ground and air transport than at baseline (80.6 and 81.4, respectively, vs 69.5 per 100 white blood cells), whereas the mean lymphocyte count was significantly lower (P < 0.05) (13.2 and 13.7, respectively, vs 22.4 per 100 white blood cells). Loading and unloading procedures caused the largest increase in heart rate. On average, the dogs spent more than 50% of the time lying down, and they remained inactive for approximately 75% of the time, except during take-off. These results suggest that transportation is stressful for dogs and that sedation with acepromazine, at the dosage and timing used, does not affect the physiological and behavioral stress responses of dogs to air transport.",,"['Bergeron, Renée', 'Scott, Shannon L.', 'Émond, Jean-Pierre', 'Mercier, Florent', 'Cook, Nigel J.', 'Schaefer, Al L.']",,,,
,PMC,Complement-Mediated Neutralization of Canine Distemper Virus In Vitro: Cross-Reaction between Vaccine Onderstepoort and Field KDK-1 Strains with Different Hemagglutinin Gene Characteristics,http://dx.doi.org/10.1128/CDLI.9.4.921-924.2002,PMC120046,,,"The properties of neutralization of antigens of canine distemper virus Onderstepoort and a recent field isolate, KDK-1, were investigated with strain-specific dog sera. A conventional neutralization assay indicated antigenic dissimilarity between the strains; however, when guinea pig complement was included in the reaction mixture, the strains were neutralized with not only the homologous but also the heterologous antibodies.",,"['Mochizuki, Masami', 'Motoyoshi, Megumi', 'Maeda, Ken', 'Kai, Kazunari']",,,,
,PMC,Screening of Neonatal Calves for Persistent Infection with Bovine Viral Diarrhea Virus by Immunohistochemistry on Skin Biopsy Samples,http://dx.doi.org/10.1128/CDLI.9.4.898-900.2002,PMC120018,,,"Detection and elimination of cattle that are persistently infected with bovine viral diarrhea virus (BVDV) is important for controlling the transmission of this virus. Colostrum-derived antibodies make the detection of persistently BVDV-infected neonatal calves cumbersome and expensive. The objective of this study was to evaluate the use of immunohistochemical staining of skin biopsy samples from neonatal calves as a method for the early detection of persistent BVDV infection. Three hundred thirty-two 1- to 4-week-old dairy calves were screened for BVDV as part of a routine control program. Formalin-fixed skin biopsy samples were stained for BVDV antigen by immunohistochemistry (IHC), and the results were compared to those of virus isolation (VI) from white blood cell preparations. Six calves were positive by both IHC and VI and remained positive for BVDV upon subsequent follow-up testing; thus, they were classified as persistently infected with BVDV. One calf was positive by VI but negative by IHC. On subsequent testing, the calf was negative by VI, suggesting that the initial VI result was due to an acute BVDV infection. One calf was positive by IHC but negative by VI. This calf remained negative by VI on follow-up testing. Immunohistochemical staining of skin biopsy samples is a reliable method for screening neonatal calves for persistent BVDV infection and would be a useful management tool as an aid for controlling and preventing BVDV infection.",,"['Grooms, Daniel L.', 'Keilen, Eric D.']",,,,
,PMC,Virus contaminations of cell cultures – A biotechnological view,http://dx.doi.org/10.1023/A:1022969101804,PMC3463984,,,"In contrast to contamination by microbes and mycoplasma, which can be relatively easily detected, viral contamination present a serious threat because of the difficulty in detecting some viruses and the lack of effective methods of treating infected cell cultures. While some viruses are capable of causing morphological changes to infected cells (e.g. cytopathic effect)which are detectable by microscopy some viral contaminations result in the integration of the viral genome as provirus, this causes no visual evidence, by means of modification of the cellular morphology. Virus production from such cell lines, are potentially dangerous for other cell cultures (in research labs)by cross contaminations, or for operators and patients (in the case of the production of injectable biologicals) because of potential infection. The only way to keep cell cultures for research, development, and the biotech industry virus-free is the prevention of such contaminations. Cell cultures can become contaminated by the following means: firstly, they may already be contaminated as primary cultures (because the source of the cells was already infected), secondly, they were contaminated due to the use of contaminated raw materials, or thirdly, they were contaminated via an animal passage. This overview describes the problems and risks associated with viral contaminations in animal cell culture, describes the origins of these contaminations as well as the most important virsuses associated with viral contaminations in cell culture. In addition, ways to prevent viral contaminations as well as measures undertaken to avoid and assess risks for viral contaminations as performed in the biotech industry are briefly described.",,"Merten, O.-W.",,,,
,PMC,Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra α-helical domain,http://dx.doi.org/10.1093/emboj/cdf327,PMC126080,,,"The key enzyme in coronavirus polyprotein processing is the viral main proteinase, M(pro), a protein with extremely low sequence similarity to other viral and cellular proteinases. Here, the crystal structure of the 33.1 kDa transmissible gastroenteritis (corona)virus M(pro) is reported. The structure was refined to 1.96 Å resolution and revealed three dimers in the asymmetric unit. The mutual arrangement of the protomers in each of the dimers suggests that M(pro) self-processing occurs in trans. The active site, comprised of Cys144 and His41, is part of a chymotrypsin-like fold that is connected by a 16 residue loop to an extra domain featuring a novel α-helical fold. Molecular modelling and mutagenesis data implicate the loop in substrate binding and elucidate S1 and S2 subsites suitable to accommodate the side chains of the P1 glutamine and P2 leucine residues of M(pro) substrates. Interactions involving the N-terminus and the α-helical domain stabilize the loop in the orientation required for trans-cleavage activity. The study illustrates that RNA viruses have evolved unprecedented variations of the classical chymotrypsin fold.",,"['Anand, Kanchan', 'Palm, Gottfried J.', 'Mesters, Jeroen R.', 'Siddell, Stuart G.', 'Ziebuhr, John', 'Hilgenfeld, Rolf']",,,,
,PMC,Molecular and Seroepidemiological Evidence of Canine Calicivirus Infections in Japan,http://dx.doi.org/10.1128/JCM.40.7.2629-2631.2002,PMC120604,,,"Calicivirus infection of dogs was epidemiologically investigated by using canine calicivirus (CaCV) strain 48 as a reference. Similar RNA polymerase gene sequences and neutralizing antibodies against CaCV were detected in 1.7% of clinical specimens and 57% of serum samples, respectively, suggesting a high prevalence of CaCV in dog populations.",,"['Mochizuki, Masami', 'Hashimoto, Michiru', 'Roerink, Frank', 'Tohya, Yukinobu', 'Matsuura, Yuichi', 'Sasaki, Nobuo']",,,,
,PMC,Helicobacter marmotae sp. nov. Isolated from Livers of Woodchucks and Intestines of Cats,http://dx.doi.org/10.1128/JCM.40.7.2513-2519.2002,PMC120550,,,"Woodchucks (Marmota monax) have a high incidence of hepatocellular carcinoma (HCC) associated with chronic infection with woodchuck hepatitis virus (WHV) and serve as a model of hepatitis B virus-associated HCC in humans. Helicobacter hepaticus, an enterohepatic helicobacter in mice, is known to cause hepatocellular adenomas and carcinomas in susceptible mouse strains. In long-term chemical bioassays conducted with B6C3F(1) mice, H. hepaticus has been regarded as a confounding factor because of its tumor-promoting activity. In order to determine if woodchucks harbor a Helicobacter sp. that might play a role in potentiating hepatic inflammation or neoplasia, a study was undertaken to determine whether woodchucks' livers were infected with a Helicobacter sp. Frozen liver samples from 20 (17 WHV-infected and 3 noninfected) woodchucks, 10 with WHV-associated hepatic tumors and 10 without tumors, were cultured by microaerobic techniques and analyzed by using genus- and species-specific helicobacter PCR primers. A 1,200-bp Helicobacter sp.-specific sequence was amplified from 14 liver samples. Southern hybridization confirmed the specific identity of the PCR products. Nine of the 10 livers with tumors had positive Helicobacter sp. identified by PCR, whereas 5 of the 10 livers without tumors were positive. By use of 16S rRNA species-specific primers for H. marmotae, two additional liver samples from the nontumor group had positive PCR amplicons confirmed by Southern hybridization. A urease-, catalase-, and oxidase-positive bacterium was isolated from one liver sample from a liver tumor-positive woodchuck. By 16S rRNA analysis and biochemical and phenotypic characteristics, the organism was classified as a novel Helicobacter sp. Subsequently, four additional bacterial strains isolated from feces of cats and characterized by biochemical, phenotypic, and 16S rRNA analysis were determined to be identical to the woodchuck isolate. We propose the name Helicobacter marmotae sp. nov. for these organisms. Further studies are required to ascertain if this novel Helicobacter sp. plays a tumor promotion role in hepadnavirus-associated tumors in woodchucks or causes enterohepatic disease in cats.",,"['Fox, James G.', 'Shen, Zeli', 'Xu, Shilu', 'Feng, Yan', 'Dangler, Charles A.', 'Dewhirst, Floyd E.', 'Paster, Bruce J.', 'Cullen, John M.']",,,,
,PMC,CD4 T-Cell-Mediated Demyelination Is Increased in the Absence of Gamma Interferon in Mice Infected with Mouse Hepatitis Virus,http://dx.doi.org/10.1128/JVI.76.14.7329-7333.2002,PMC136326,,,"Mice infected with the murine coronavirus, mouse hepatitis virus, strain JHM (MHV) develop an immune-mediated demyelinating encephalomyelitis. Adoptive transfer of MHV-immune splenocytes depleted of either CD4 or CD8 T cells to infected mice deficient in recombination activation gene 1 resulted in demyelination. We showed previously that the process of CD8 T-cell-mediated demyelination was strongly dependent on the expression of gamma interferon (IFN-γ) by donor cells. In this report, we show, in contrast, that demyelination and lymphocyte infiltration were increased in recipients of IFN-γ(−/−) CD4 T cells when compared to levels in mice receiving C57BL/6 CD4 T cells.",,"['Pewe, Lecia', 'Haring, Jodie', 'Perlman, Stanley']",,,,
,PMC,Perineuronal Oligodendrocytes Protect against Neuronal Apoptosis through the Production of Lipocalin-Type Prostaglandin D Synthase in a Genetic Demyelinating Model,http://dx.doi.org/10.1523/JNEUROSCI.22-12-04885.2002,PMC6757748,,,"The genetic demyelinating mouse “twitcher” is a model of the human globoid cell leukodystrophy, caused by galactosylceramidase (GALC) deficiency. Demyelination in the twitcher brain is secondary to apoptotic death of oligodendrocytes (OLs). Lipocalin-type prostaglandin (PG) D synthase (L-PGDS), a protein expressed in mature OLs, was progressively upregulated in twitcher OLs; whereas expression of OL-associated proteins such as carbonic anhydrase II, myelin basic protein, and myelin-associated glycoprotein was downregulated during demyelination in twitcher brains. The upregulation of L-PGDS was more remarkable in perineuronal OLs than in interfascicular OLs. A larger number of L-PGDS-positive OLs was found in selected fiber tracts of twitcher brains where fewer apoptotic cells were detected. The distribution of L-PGDS-positive OLs was inversely related to the severity of demyelination, as assessed by accumulation of scavenger macrophages. Mice doubly deficient for L-PGDS and GALC disclosed a large number of apoptotic neurons, which were never seen in twitcher brains, in addition to an increased number of apoptotic OLs. A linear positive correlation was observed between the population of L-PGDS-positive OLs in the twitcher brain and the ratio of apoptotic nuclei in the double mutant versus those in the twitcher, suggesting a dose-dependent effect of L-PGDS against apoptosis. These lines of evidence suggest that L-PGDS is an anti-apoptotic molecule protecting neurons and OLs from apoptosis in the twitcher mouse. This is a novel example of OL–neuronal interaction.",,"['Taniike, Masako', 'Mohri, Ikuko', 'Eguchi, Naomi', 'Beuckmann, Carsten T.', 'Suzuki, Kinuko', 'Urade, Yoshihiro']",,,,
,PMC,Salmonella Muenster infection in a dairy herd,,PMC339296,,,"The overall purpose of this study was to provide information on animal and occupational health associated with the infection of a dairy herd with Salmonella Muenster that would be useful in the management of dairy herds so infected. This retrospective, longitudinal report records a 2-year infection of a 140-cow dairy herd with S. Muenster, which was likely introduced by additions to the herd. Six cows aborted or had diarrhea due to salmonellosis in the last trimester of pregnancy. Additions to the herd and the presence of animals that had not received an Escherichia coli bacterin-toxoid were risk factors for salmonellosis. One neonate died, and 24 of 36 calves born between November 1998 and May 1999 had diarrhea by 1 mo of age. Initially, over 60% of the cows were fecal positive; within 6 months, all cows but 1 had become infected. The intermittent shedding of the organism and the eventual zero prevalence highlight the inappropriateness of extensive culling as an eradication strategy. Cultures of the bulk-tank milk filters were more sensitive than cultures of the bulk-tank milk samples at detecting S. Muenster. Two months after the index case, S. Muenster was cultured from the milk of 7.8% of the cows. Positive fecal or milk cultures were not associated with impaired health or production. The herd's milk was a zoonotic risk, but contact with infected animals was not. The organism spread easily between operations, likely via manure-contaminated clothing and footwear.",,"['Radke, Brian R.', 'McFall, Margaret', 'Radostits, Steve M.']",,,,
,PMC,"Effectiveness of Reverse Transcription-PCR, Virus Isolation, and Enzyme-Linked Immunosorbent Assay for Diagnosis of Influenza A Virus Infection in Different Age Groups",http://dx.doi.org/10.1128/JCM.40.6.2051-2056.2002,PMC130702,,,"The degrees of effectiveness of reverse transcription (RT)-PCR, virus isolation, and antigen enzyme-linked immunosorbent assay (ELISA) for the detection of influenza A virus were evaluated with nasopharyngeal swabs from 150 patients (1 week to 86 years old) with influenza A virus infection. RT-PCR had a sensitivity for influenza A virus in stock virus preparations 10(3) times higher than virus isolation and 10(6) to 10(7) times higher than ELISA. The detection rate achieved by RT-PCR in clinical samples was clearly higher (93%) than that by virus isolation (80%) and ELISA (62%). Despite low overall detection rates achieved by antigen ELISA, samples from patients younger than 5 years old yielded higher-than-average rates in this rapid assay (88%). The likelihood of negative results in the ELISA increased significantly with increasing age of the patient (P < 0.01). The degrees of effectiveness of RT-PCR and virus isolation were not influenced by the age of the patient. Neither influenza immunizations nor the interval between onset of symptoms and laboratory investigation (mean, 4.7 days; standard deviation, 3.3 days) affected results obtained by the three test systems. Our results demonstrate that the ELISA is reliable for rapid laboratory diagnosis of influenza in infants and young children, but for older patients application of RT-PCR or virus isolation is necessary to avoid false negative results.",,"['Steininger, Christoph', 'Kundi, Michael', 'Aberle, Stephan W.', 'Aberle, Judith H.', 'Popow-Kraupp, Theresia']",,,,
,PMC,Skin tumors in aging Long Evans rats.,,PMC2594380,,,"We report 25 cases of skin neoplasm observed among 30 Long Evans rats serving as controls in a psychosocial behavioral study conducted in the Vivarium at Charles R. Drew University, Los Angeles, CA. The animals were 10 weeks old at the beginning of the study. All the skin tumors developed at 18 to 26 months of age and slowly enlarged over a period of 9 months. Multiple nodules occurred in 8 males and 6 females. None of the tumors regressed. The tumors were located around the hind leg and dorso-medial area and measured 1 to 2 cm. Physical examination revealed firm well demarcated dermal masses. Most of the tumor nodules were intradermal, and some had a central ulcerated or keratin-filled core. Microscopic examination performed on some of the tumors showed findings of classic Keratoacanthoma, whereas others showed histologic features suggestive of squamous cell carcinoma. These findings indicate a high rate (83%) of spontaneous skin neoplasms among aging Long Evans rats. To our knowledge, such a high rate of skin neoplasms in aged rodents has not been described in the literature. Furthermore, further studies should be undertaken to confirm these findings and to assess whether these rodents might serve as a model for studying the alterations in the immune system with aging.",,"['Esfandiari, Adeleh', 'Loya, Theresa', 'Lee, Jeffrey L.']",,,,
,PMC,"Respiratory Syncytial Virus Infection of Human Airway Epithelial Cells Is Polarized, Specific to Ciliated Cells, and without Obvious Cytopathology",http://dx.doi.org/10.1128/JVI.76.11.5654-5666.2002,PMC137037,,,"Gene therapy for cystic fibrosis (CF) lung disease requires efficient gene transfer to airway epithelial cells after intralumenal delivery. Most gene transfer vectors so far tested have not provided the efficiency required. Although human respiratory syncytial virus (RSV), a common respiratory virus, is known to infect the respiratory epithelium, the mechanism of infection and the epithelial cell type targeted by RSV have not been determined. We have utilized human primary airway epithelial cell cultures that generate a well-differentiated pseudostratified mucociliary epithelium to investigate whether RSV infects airway epithelium via the lumenal (apical) surface. A recombinant RSV expressing green fluorescent protein (rgRSV) infected epithelial cell cultures with high gene transfer efficiency when applied to the apical surface but not after basolateral inoculation. Analyses of the cell types infected by RSV revealed that lumenal columnar cells, specifically ciliated epithelial cells, were targeted by RSV and that cultures became susceptible to infection as they differentiated into a ciliated phenotype. In addition to infection of ciliated cells via the apical membrane, RSV was shed exclusively from the apical surface and spread to neighboring ciliated cells by the motion of the cilial beat. Gross histological examination of cultures infected with RSV revealed no evidence of obvious cytopathology, suggesting that RSV infection in the absence of an immune response can be tolerated for >3 months. Therefore, rgRSV efficiently transduced the airway epithelium via the lumenal surface and specifically targeted ciliated airway epithelial cells. Since rgRSV appears to breach the lumenal barriers encountered by other gene transfer vectors in the airway, this virus may be a good candidate for the development of a gene transfer vector for CF lung disease.",,"['Zhang, Liqun', 'Peeples, Mark E.', 'Boucher, Richard C.', 'Collins, Peter L.', 'Pickles, Raymond J.']",,,,
,PMC,"Membrane Association and Dimerization of a Cysteine-Rich, 16-Kilodalton Polypeptide Released from the C-Terminal Region of the Coronavirus Infectious Bronchitis Virus 1a Polyprotein",http://dx.doi.org/10.1128/JVI.76.12.6257-6267.2002,PMC136229,,,"More than 10 mature proteins processed from coronavirus gene 1-encoded polyproteins have been identified in virus-infected cells. Here, we report the identification of the most C-terminal cleavage product of the 1a polyprotein as a 16-kDa protein in infectious bronchitis virus-infected Vero cells. Indirect immunofluorescence demonstrated that the protein exhibits a distinct perinuclear punctate staining pattern, suggesting that it is associated with cellular membranes. Positive staining observed on nonpermeabilized cells indicates that the protein may get transported to the cell surface, but no secretion of the protein out of the cells was observed. Treatment of the membrane fraction prepared from cells expressing the 16-kDa protein with Triton X-100, a high pH, and a high concentration of salts showed that the protein may be tightly associated with intracellular membranes. Dual-labeling experiments demonstrated that the 16-kDa protein colocalized with the 5′-bromouridine 5′-triphosphate-labeled viral RNA, suggesting that it may be associated with the viral replication machinery. Sequence comparison of the 16-kDa protein with the equivalent products of other coronaviruses showed multiple conserved cysteine residues, and site-directed mutagenesis studies revealed that these conserved residues may contribute to dimerization of the 16-kDa protein. Furthermore, increased accumulation of the 16-kDa protein upon stimulation with epidermal growth factor was observed, providing preliminary evidence that the protein might be involved in the growth factor signaling pathway.",,"['Ng, Lisa F. P.', 'Liu, D. X.']",,,,
,PMC,The Synthesis of Minus-Strand RNA of Bamboo Mosaic Potexvirus Initiates from Multiple Sites within the Poly(A) Tail,http://dx.doi.org/10.1128/JVI.76.12.6114-6120.2002,PMC136226,,,"The 3′ terminus of the bamboo mosaic potexvirus (BaMV) contains a poly(A) tail, the 5′ portion of which participates in the formation of an RNA pseudoknot required for BaMV RNA replication. Recombinant RNA-dependent RNA polymerase (RdRp) of BaMV binds to the pseudoknot poly(A) tail in gel mobility shift assays (C.-Y. Huang, Y.-L. Huang, M. Meng, Y.-H. Hsu, and C.-H. Tsai, J. Virol. 75:2818-2824, 2001). Approximately 20 nucleotides of the poly(A) tail adjacent to the 3′ untranslated region (UTR) are protected from diethylpyrocarbonate modification, suggesting that this region may be used to initiate minus-strand RNA synthesis. The 5′ terminus of the minus-strand RNA synthesized by the RdRp in vitro was examined using 5′ rapid amplification of cDNA ends (RACE) and DNA sequencing. Minus-strand RNA synthesis was found to initiate from several positions within the poly(A) tail, with the highest frequency of initiation being from the 7th to the 10th adenylates counted from the 5′-most adenylate of the poly(A) tail. Sequence analyses of BaMV progeny RNAs recovered from Nicotiana benthamiana protoplasts which were inoculated with mutants containing a mutation at the 1st, 4th, 7th, or 16th position of the poly(A) tail suggested the existence of variable initiation sites, similar to those found in 5′ RACE experiments. We deduce that the initiation site for minus-strand RNA synthesis is not fixed at one position but resides opposite one of the 15 adenylates of the poly(A) tail immediately downstream of the 3′ UTR of BaMV genomic RNA.",,"['Cheng, Jai-Hong', 'Peng, Chi-Weng', 'Hsu, Yau-Heiu', 'Tsai, Ching-Hsiu']",,,,
,PMC,Murine Coronavirus Replication-Induced p38 Mitogen-Activated Protein Kinase Activation Promotes Interleukin-6 Production and Virus Replication in Cultured Cells,http://dx.doi.org/10.1128/JVI.76.12.5937-5948.2002,PMC136219,,,"Analyses of mitogen-activated protein kinases (MAPKs) in a mouse hepatitis virus (MHV)-infected macrophage-derived J774.1 cell line showed activation of two MAPKs, p38 MAPK and c-Jun N-terminal kinase (JNK), but not of extracellular signal-regulated kinase (ERK). Activation of MAPKs was evident by 6 h postinfection. However, UV-irradiated MHV failed to activate MAPKs, which demonstrated that MHV replication was necessary for their activation. Several other MHV-permissive cell lines also showed activation of both p38 MAPK and JNK, which indicated that the MHV-induced stress-kinase activation was not restricted to any particular cell type. The upstream kinase responsible for activating MHV-induced p38 MAPK was the MAPK kinase 3. Experiments with a specific inhibitor of p38 MAPK, SB 203580, demonstrated that MHV-induced p38 MAPK activation resulted in the accumulation of interleukin-6 (IL-6) mRNAs and an increase in the production of IL-6, regardless of MHV-induced general host protein synthesis inhibition. Furthermore, MHV production was suppressed in SB 203580-treated cells, demonstrating that activated p38 MAPK played a role in MHV replication. The reduced MHV production in SB 203580-treated cells was, at least in part, due to a decrease in virus-specific protein synthesis and virus-specific mRNA accumulation. Interestingly, there was a transient increase in the amount of phosphorylation of the translation initiation factor 4E (eIF4E) in infected cells, and this eIF4E phosphorylation was p38 MAPK dependent; it is known that phosphorylated eIF4E enhances translation rates of cap-containing mRNAs. Furthermore, the upstream kinase responsible for eIF4E phosphorylation, MAPK-interacting kinase 1, was also phosphorylated and activated in response to MHV infection. Our data suggested that host cells, in response to MHV replication, activated p38 MAPK, which subsequently phosphorylated eIF4E to efficiently translate certain host proteins, including IL-6, during virus-induced severe host protein synthesis inhibition. MHV utilized this p38 MAPK-dependent increase in eIF4E phosphorylation to promote virus-specific protein synthesis and subsequent progeny virus production. Enhancement of virus-specific protein synthesis through virus-induced eIF4E activation has not been reported in any other viruses.",,"['Banerjee, Sangeeta', 'Narayanan, Krishna', 'Mizutani, Tetsuya', 'Makino, Shinji']",,,,
,PMC,Binding of Transmissible Gastroenteritis Coronavirus to Cell Surface Sialoglycoproteins,http://dx.doi.org/10.1128/JVI.76.12.6037-6043.2002,PMC136196,,,"The surface glycoprotein S of transmissible gastroenteritis virus (TGEV) has two binding activities. (i) Binding to porcine aminopeptidase N (pAPN) is essential for the initiation of infection. (ii) Binding to sialic acid residues on glycoproteins is dispensable for the infection of cultured cells but is required for enteropathogenicity. By comparing parental TGEV with mutant viruses deficient in the sialic acid binding activity, we determined the contributions of both binding activities to the attachment of TGEV to cultured cells. In the presence of a functional sialic acid binding activity, the amount of virus bound to two different porcine cell lines was increased sixfold compared to the binding of the mutant viruses. The attachment of parental virus was reduced to levels observed with the mutants when sialic acid containing inhibitors was present or when the cells were pretreated with neuraminidase. In virus overlay binding assays with immobilized cell surface proteins, the mutant virus only recognized pAPN. In addition, the parental virus bound to a high-molecular-mass sialoglycoprotein. The recognition of pAPN was sensitive to reducing conditions and was not dependent on sialic acid residues. On the other hand, binding to the sialic acid residues of the high-molecular-mass glycoprotein was observed regardless of whether the cellular proteins had been separated under reducing or nonreducing conditions. We propose that binding to a surface sialoglycoprotein is required for TGEV as a primary attachment site to initiate infection of intestinal cells. This concept is discussed in the context of other viruses that use two different receptors to infect cells.",,"['Schwegmann-Weßels, Christel', 'Zimmer, Gert', 'Laude, Hubert', 'Enjuanes, Luis', 'Herrler, Georg']",,,,
,PMC,Thermodynamic and phylogenetic prediction of RNA secondary structures in the coding region of hepatitis C virus.,,PMC1370300,,,"The existence and functional importance of RNA secondary structure in the replication of positive-stranded RNA viruses is increasingly recognized. We applied several computational methods to detect RNA secondary structure in the coding region of hepatitis C virus (HCV), including thermodynamic prediction, calculation of free energy on folding, and a newly developed method to scan sequences for covariant sites and associated secondary structures using a parsimony-based algorithm. Each of the prediction methods provided evidence for complex RNA folding in the core- and NS5B-encoding regions of the genome. The positioning of covariant sites and associated predicted stem-loop structures coincided with thermodynamic predictions of RNA base pairing, and localized precisely in parts of the genome with marked suppression of variability at synonymous sites. Combined, there was evidence for a total of six evolutionarily conserved stem-loop structures in the NS5B-encoding region and two in the core gene. The virus most closely related to HCV, GB virus-B (GBV-B) also showed evidence for similar internal base pairing in its coding region, although predictions of secondary structures were limited by the absence of comparative sequence data for this virus. While the role(s) of stem-loops in the coding region of HCV and GBV-B are currently unknown, the structure predictions in this study could provide the starting point for functional investigations using recently developed self-replicating clones of HCV.",,"['Tuplin, Andrew', 'Wood, Jonny', 'Evans, David J', 'Patel, Arvind H', 'Simmonds, Peter']",,,,
,PMC,"Crystal structure of murine sCEACAM1a[1,4]: a coronavirus receptor in the CEA family",http://dx.doi.org/10.1093/emboj/21.9.2076,PMC125375,,,"CEACAM1 is a member of the carcinoembryonic antigen (CEA) family. Isoforms of murine CEACAM1 serve as receptors for mouse hepatitis virus (MHV), a murine coronavirus. Here we report the crystal structure of soluble murine sCEACAM1a[1,4], which is composed of two Ig-like domains and has MHV neutralizing activity. Its N-terminal domain has a uniquely folded CC′ loop that encompasses key virus-binding residues. This is the first atomic structure of any member of the CEA family, and provides a prototypic architecture for functional exploration of CEA family members. We discuss the structural basis of virus receptor activities of murine CEACAM1 proteins, binding of Neisseria to human CEACAM1, and other homophilic and heterophilic interactions of CEA family members.",,"['Tan, Kemin', 'Zelus, Bruce D.', 'Meijers, Rob', 'Liu, Jin-huan', 'Bergelson, Jeffrey M.', 'Duke, Norma', 'Zhang, Rongguang', 'Joachimiak, Andrzej', 'Holmes, Kathryn V.', 'Wang, Jia-huai']",,,,
,PMC,Evaluation of the Directigen FluA+B Test for Rapid Diagnosis of Influenza Virus Type A and B Infections,http://dx.doi.org/10.1128/JCM.40.5.1675-1680.2002,PMC130655,,,"Directigen FluA+B (BD Diagnostic Systems, Sparks, Md.), a new rapid test for the detection of influenza virus types A and B, was evaluated with nasopharyngeal aspirate specimens collected from 250 patients in comparison with culture and direct fluorescent antigen (DFA) detection tests. The patients studied were predominantly children, 80% being ≤6 years old. Specimens negative by culture but positive by the Directigen FluA+B or DFA tests were analyzed by reverse transcription-PCR to resolve the discrepant results. The resolved sensitivity, specificity, and positive and negative predictive values of the Directigen FluA+B test for influenza virus type A were 96%, 99.6%, 96%, and 99.6%, respectively, and for influenza virus type B they were 87.5%, 96.8%, 80%, and 98%, respectively. Storage of nasopharyngeal aspirates in virus transport medium at 2 to 8°C for 48 h had little adverse effect on the detection of influenza virus type A, but diagnosis of influenza virus type B is best carried out with fresh specimens. The test detected a range of human and animal influenza virus A subtypes, including the H5N1 and H9N2 viruses that recently caused human disease in Hong Kong.",,"['Chan, K. H.', 'Maldeis, N.', 'Pope, W.', 'Yup, A.', 'Ozinskas, A.', 'Gill, J.', 'Seto, W. H.', 'Shortridge, K. F.', 'Peiris, J. S. M.']",,,,
,PMC,Stabilization of a Full-Length Infectious cDNA Clone of Transmissible Gastroenteritis Coronavirus by Insertion of an Intron,http://dx.doi.org/10.1128/JVI.76.9.4655-4661.2002,PMC155106,,,The stable propagation of a full-length transmissible gastroenteritis coronavirus (TGEV) cDNA in Escherichia coli cells as a bacterial artificial chromosome has been considerably improved by the insertion of an intron to disrupt a toxic region identified in the viral genome. The viral RNA was expressed in the cell nucleus under the control of the cytomegalovirus promoter and the intron was efficiently removed during translocation of this RNA to the cytoplasm. The insertion in two different positions allowed stable plasmid amplification for at least 200 generations. Infectious TGEV was efficiently recovered from cells transfected with the modified cDNAs.,,"['González, José M.', 'Pénzes, Zoltan', 'Almazán, Fernando', 'Calvo, Enrique', 'Enjuanes, Luis']",,,,
,PMC,Interaction of the Coronavirus Nucleoprotein with Nucleolar Antigens and the Host Cell,http://dx.doi.org/10.1128/JVI.76.10.5233-5250.2002,PMC136173,,,"Coronavirus nucleoproteins (N proteins) localize to the cytoplasm and the nucleolus, a subnuclear structure, in both virus-infected primary cells and in cells transfected with plasmids that express N protein. The nucleolus is the site of ribosome biogenesis and sequesters cell cycle regulatory complexes. Two of the major components of the nucleolus are fibrillarin and nucleolin. These proteins are involved in nucleolar assembly and ribosome biogenesis and act as chaperones for the import of proteins into the nucleolus. We have found that fibrillarin is reorganized in primary cells infected with the avian coronavirus infectious bronchitis virus (IBV) and in continuous cell lines that express either IBV or mouse hepatitis virus N protein. Both N protein and a fibrillarin-green fluorescent protein fusion protein colocalized to the perinuclear region and the nucleolus. Pull-down assays demonstrated that IBV N protein interacted with nucleolin and therefore provided a possible explanation as to how coronavirus N proteins localize to the nucleolus. Nucleoli, and proteins that localize to the nucleolus, have been implicated in cell growth-cell cycle regulation. Comparison of cells expressing IBV N protein with controls indicated that cells expressing N protein had delayed cellular growth. This result could not to be attributed to apoptosis. Morphological analysis of these cells indicated that cytokinesis was disrupted, an observation subsequently found in primary cells infected with IBV. Coronaviruses might therefore delay the cell cycle in interphase, where maximum translation of viral mRNAs can occur.",,"['Chen, Hongying', 'Wurm, Torsten', 'Britton, Paul', 'Brooks, Gavin', 'Hiscox, Julian A.']",,,,
,PMC,Genetic Evidence for a Structural Interaction between the Carboxy Termini of the Membrane and Nucleocapsid Proteins of Mouse Hepatitis Virus,http://dx.doi.org/10.1128/JVI.76.10.4987-4999.2002,PMC136159,,,"The coronavirus membrane (M) protein is the most abundant virion protein and the key component in viral assembly and morphogenesis. The M protein of mouse hepatitis virus (MHV) is an integral membrane protein with a short ectodomain, three transmembrane segments, and a large carboxy-terminal endodomain facing the interior of the viral envelope. The carboxy terminus of MHV M has previously been shown to be extremely sensitive to mutation, both in a virus-like particle expression system and in the intact virion. We have constructed a mutant, MΔ2, containing a two-amino-acid truncation of the M protein that was previously thought to be lethal. This mutant was isolated by means of targeted RNA recombination with a powerful host range-based selection allowed by the interspecies chimeric virus fMHV (MHV containing the ectodomain of the feline infectious peritonitis virus S protein). Analysis of multiple second-site revertants of the MΔ2 mutant has revealed changes in regions of both the M protein and the nucleocapsid (N) protein that can compensate for the loss of the last two residues of the M protein. Our data thus provide the first genetic evidence for a structural interaction between the carboxy termini of the M and N proteins of MHV. In addition, this work demonstrates the efficacy of targeted recombination with fMHV for the systematic genetic analysis of coronavirus structural protein interactions.",,"['Kuo, Lili', 'Masters, Paul S.']",,,,
,PMC,Disease in endangered metapopulations: the importance of alternative hosts.,http://dx.doi.org/10.1098/rspb.2001.1667,PMC1690941,,,"Conventional applications of metapopulation theory have suggested that increasing migration between patches is usually good for conservation. A recent analysis by Hess has pointed out a possible exception to this: when infectious disease is present, migration may promote disease spread and therefore increase local extinction. We extend Hess's model to discuss this problem: when infections have spilled over from more abundant alternative hosts. This is often the case for species of conservation concern, and we find that Hess's conclusions must be substantially modified. We use deterministic analytic and stochastic numerical approaches to show that movement between patches will rarely have a negative impact, even when the probability of external infection is low.",,"['Gog, Julia', 'Woodroffe, Rosie', 'Swinton, Jonathan']",,,,
,PMC,"Comparison of reverse transcription polymerase chain reaction, immunohistochemistry, and in situ hybridization for the detection of porcine epidemic diarrhea virus in pigs",,PMC226992,,,"Reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry, and in situ hybridization were compared for the detection of porcine epidemic diarrhea virus (PEDV). Fifteen piglets experimentally infected with PEDV were used in the study. In addition, 94 diarrheic piglets submitted to the Department of Veterinary Pathology in Seoul National University for diagnosis of PEDV infection were used to compare the 3 methods. Antigen and nucleic acid of PEDV were detected in 15/15, 13/15, and 14/15 of the intestinal and fecal samples from the PEDV-inoculated pigs by RT-PCR, immunohistochemistry, and in situ hybridization, respectively. The virus was isolated from 15/15 of the jejunal samples from the PEDV-inoculated pigs. Neither PEDV antigen nor PEDV nucleic acid was detected in the intestinal and fecal samples from mock-infected control pigs. Of the 94 samples, 63 were positive for PEDV by all 3 techniques. Six samples were positive for PEDV by immunohistochemistry and in situ hybridization. Three samples were positive for PEDV by in situ hybridization and RT-PCR. Seven samples were positive for PEDV by RT-PCR. Although RT-PCR identified the presence of PEDV more frequently than the other methods, when only formalin-fixed tissues are submitted, immunohistochemistry and in situ hybridization would be useful methods for the detection of PEDV antigen and nucleic acid.",,"['Kim, Okjin', 'Chae, Chanhee']",,,,
,PMC,RNA Replication of Mouse Hepatitis Virus Takes Place at Double-Membrane Vesicles,http://dx.doi.org/10.1128/JVI.76.8.3697-3708.2002,PMC136101,,,"The replication complexes (RCs) of positive-stranded RNA viruses are intimately associated with cellular membranes. To investigate membrane alterations and to characterize the RC of mouse hepatitis virus (MHV), we performed biochemical and ultrastructural studies using MHV-infected cells. Biochemical fractionation showed that all 10 of the MHV gene 1 polyprotein products examined pelleted with the membrane fraction, consistent with membrane association of the RC. Furthermore, MHV gene 1 products p290, p210, and p150 and the p150 cleavage product membrane protein 1 (MP1, also called p44) were resistant to extraction with Triton X-114, indicating that they are integral membrane proteins. The ultrastructural analysis revealed double-membrane vesicles (DMVs) in the cytoplasm of MHV-infected cells. The DMVs were found either as separate entities or as small clusters of vesicles. To determine whether MHV proteins and viral RNA were associated with the DMVs, we performed immunocytochemistry electron microscopy (IEM). We found that the DMVs were labeled using an antiserum directed against proteins derived from open reading frame 1a of MHV. By electron microscopy in situ hybridization (ISH) using MHV-specific RNA probes, DMVs were highly labeled for both gene 1 and gene 7 sequences. By combined ISH and IEM, positive-stranded RNA and viral proteins localized to the same DMVs. Finally, viral RNA synthesis was detected by labeling with 5-bromouridine 5′-triphosphate. Newly synthesized viral RNA was found to be associated with the DMVs. We conclude from these data that the DMVs carry the MHV RNA replication complex and are the site of MHV RNA synthesis.",,"['Gosert, Rainer', 'Kanjanahaluethai, Amornrat', 'Egger, Denise', 'Bienz, Kurt', 'Baker, Susan C.']",,,,
,PMC,Experimental Inoculation of Conventional Pigs with Porcine Reproductive and Respiratory Syndrome Virus and Porcine Circovirus 2,http://dx.doi.org/10.1128/JVI.76.7.3232-3239.2002,PMC136035,,,"Postweaning multisystemic wasting syndrome (PMWS) is a disease of nursery and fattening pigs characterized by growth retardation, paleness of the skin, dyspnea, and increased mortality rates. Porcine circovirus 2 (PCV2) has been demonstrated to be the cause of PMWS. However, other factors are needed for full development of the syndrome, and porcine reproductive and respiratory syndrome virus (PRRSV) infection has been suggested to be one of them. Twenty-four conventional 5-week-old pigs were distributed in four groups: control (n = 5), PRRSV inoculated (n = 5), PCV2 inoculated (n = 7), and PRRSV and PCV2 inoculated (n = 7). The two groups inoculated with PRRSV showed growth retardation. Pigs inoculated with both PRRSV and PCV2 had increased rectal temperature. One of these pigs developed wasting, had severe respiratory distress, and died. The most important microscopic lesion in pigs inoculated with PCV2 was lymphocyte depletion with histiocytic infiltration of the lymphoid organs, more severe and in a wider range of tissues in doubly inoculated pigs. Interstitial pneumonia was observed in the three inoculated groups. PCV2 nucleic acid was found by in situ hybridization in larger amounts and in a wider range of lymphoid tissues in PRRSV- and PCV2-inoculated than in PCV2-inoculated pigs. TaqMan PCR was performed to quantify the PCV2 loads in serum during the experiment. PCV2 loads were higher in doubly inoculated pigs than in pigs inoculated with PCV2 alone. These findings indicate that severe disease can be reproduced in conventional 5-week-old pigs by inoculation of PRRSV and PCV2. Moreover, these results support the hypothesis that PRRSV infection enhances PCV2 replication.",,"['Rovira, A.', 'Balasch, M.', 'Segalés, J.', 'García, L.', 'Plana-Durán, J.', 'Rosell, C.', 'Ellerbrok, H.', 'Mankertz, A.', 'Domingo, M.']",,,,
,PMC,Apical Budding of a Recombinant Influenza A Virus Expressing a Hemagglutinin Protein with a Basolateral Localization Signal,http://dx.doi.org/10.1128/JVI.76.7.3544-3553.2002,PMC136015,,,"Influenza virions bud preferentially from the apical plasma membrane of infected epithelial cells, by enveloping viral nucleocapsids located in the cytosol with its viral integral membrane proteins, i.e., hemagglutinin (HA), neuraminidase (NA), and M2 proteins, located at the plasma membrane. Because individually expressed HA, NA, and M2 proteins are targeted to the apical surface of the cell, guided by apical sorting signals in their transmembrane or cytoplasmic domains, it has been proposed that the polarized budding of influenza virions depends on the interaction of nucleocapsids and matrix proteins with the cytoplasmic domains of HA, NA, and/or M2 proteins. Since HA is the major protein component of the viral envelope, its polarized surface delivery may be a major force that drives polarized viral budding. We investigated this hypothesis by infecting MDCK cells with a transfectant influenza virus carrying a mutant form of HA (C560Y) with a basolateral sorting signal in its cytoplasmic domain. C560Y HA was expressed nonpolarly on the surface of infected MDCK cells. Interestingly, viral budding remained apical in C560Y virus-infected cells, and so did the location of NP and M1 proteins at late times of infection. These results are consistent with a model in which apical viral budding is a shared function of various viral components rather than a role of the major viral envelope glycoprotein HA.",,"['Mora, Rosalia', 'Rodriguez-Boulan, Enrique', 'Palese, Peter', 'García-Sastre, Adolfo']",,,,
,PMC,Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study,,PMC100316,,,"OBJECTIVE: To investigate the importance of sensitisation and exposure to allergens and viral infection in precipitating acute asthma in adults resulting in admission to hospital. DESIGN: Case-control study. SETTING: Large district general hospital. PARTICIPANTS: 60 patients aged 17-50 admitted to hospital over a year with acute asthma, matched with two controls: patients with stable asthma recruited from the outpatient department and patients admitted to hospital with non-respiratory conditions (inpatient controls). MAIN OUTCOME MEASURES: Atopic status (skin testing and total and specific IgE), presence of common respiratory viruses and atypical bacteria (polymerase chain reaction), dust samples from homes, and exposure to allergens (enzyme linked immunosorbent assay (ELISA): Der p 1, Fel d 1, Can f 1, and Bla g 2). RESULTS: Viruses were detected in 31 of 177 patients. The difference in the frequency of viruses detected between the groups was significant (admitted with asthma 26%, stable asthma 18%, inpatient controls 9%; P=0.04). A significantly higher proportion of patients admitted with asthma (66%) were sensitised and exposed to either mite, cat, or dog allergen than patients with stable asthma (37%) and inpatient controls (15%; P<0.001). Being sensitised and exposed to allergens was an independent associate of the group admitted to hospital (odds ratio 2.3, 95% confidence interval 1.0 to 5.4; P=0.05), whereas the combination of sensitisation, high exposure to one or more allergens, and viral detection considerably increased the risk of being admitted with asthma (8.4, 2.1 to 32.8; P=0.002). CONCLUSIONS: Allergens and viruses may act together to exacerbate asthma.",,"['Green, Rosalind M', 'Custovic, Adnan', 'Sanderson, Gwen', 'Hunter, Jenny', 'Johnston, Sebastian L', 'Woodcock, Ashley']",,,,
,PMC,Measles Virus Preferentially Transduces the Basolateral Surface of Well-Differentiated Human Airway Epithelia,,PMC153805,,,"Measles virus (MV) is typically spread by aerosol droplets and enters via the respiratory tract. The progression of MV infection has been widely studied; yet, the pathway for virus entry in polarized human airway epithelia has not been investigated. Herein we report the use of a replication-competent Edmonston vaccine strain of MV expressing enhanced green fluorescent protein (MV-eGFP) to infect primary cultures of well-differentiated human airway epithelia. Previous studies with polarized Caco-2 cells (intestine-derived human epithelia) and MDCK cells (kidney-derived canine epithelia) demonstrated that MV primarily infected and exited the apical surface. In striking contrast, our results indicate that MV preferentially transduces human airway cells from the basolateral surface; however, virus release remains in an apical direction. When MV-eGFP was applied apically or basolaterally to primary cultures of airway epithelia, discrete foci of eGFP expression appeared and grew; however, the cell layer integrity was maintained for the duration of the study (7 days). Interestingly, utilizing immunohistochemistry and confocal microscopy, we observed widespread expression of the receptor for the vaccine strain of MV (CD46) at greatest abundance on the apical surface of the differentiated human airway epithelia as well as in human tracheal tissue sections. These data suggest that the progression of MV infection through the respiratory epithelium may involve pathways other than direct binding and entry through the apical surface of airway epithelia.",,"['Sinn, Patrick L.', 'Williams, Greg', 'Vongpunsawad, Sompong', 'Cattaneo, Roberto', 'McCray, Paul B.']",,,,
,PMC,"The C-terminal domain, but not the interchain disulphide, is required for the activity and intracellular trafficking of aminopeptidase A.",,PMC1222376,,,"Mammalian aminopeptidase A (APA; glutamyl aminopeptidase; EC 3.4.11.7) is a type II membrane-spanning protein consisting of a short N-terminal cytosolic domain, a single transmembrane domain and a large extracellular C-terminal domain containing the active site. The extracellular domain consists of a 107 kDa domain, containing the zinc-binding motif and all the residues involved in catalysis, separated by a protease-susceptible hinge region from the 45 kDA C-terminal domain of unknown function. To investigate the role of the 45 kDa domain, a construct of murine APA (G594Delta) lacking this C-terminal domain was expressed in COS-1 cells. This truncated form of APA, although expressed, lacked enzymic activity and failed to reach the cell surface. Confocal immunofluorescence microscopy revealed that G594Delta co-localized with the lectin concanavalin A and had a similar staining pattern as protein disulphide-isomerase, indicating that it was retained in the endoplasmic reticulum. Thus the C-terminal 45 kDa domain appears to be acting like a pro-domain and seems to be required for the correct folding and trafficking of APA. In contrast, mutation of cysteine-43 to serine, which is involved in the disulphide-linkage of the APA homodimer, did not affect the enzymic activity, cellular location or rate of trafficking through the secretory pathway of APA.",,"['Ofner, Lisa D', 'Hooper, Nigel M']",,,,
,PMC,Experimental Infection of Domestic Cats with Bartonella koehlerae and Comparison of Protein and DNA Profiles with Those of Other Bartonella Species Infecting Felines,http://dx.doi.org/10.1128/JCM.40.2.466-474.2002,PMC153398,,,"Bartonella koehlerae, a recently described feline Bartonella species, was isolated from two naturally infected cats in northern California. We experimentally infected domestic cats with B. koehlerae to establish the microbiological and immunological characteristics of this infection in cats and to compare it to infections with those caused by B. henselae and B. clarridgeiae. Four cats were inoculated intradermally with B. koehlerae (8.6 × 10(7) to 3.84 × 10(8) CFU/ml). None of the cats presented any obvious clinical signs, but all cats developed bacteremia, which peaked at 3.36 × 10(4) to 1.44 × 10(6) CFU/ml of blood between day 14 and day 36 postinoculation. B. koehlerae-inoculated cats had a bacteremia duration (mean, 74 days) shorter than did cats inoculated with B. clarridgeiae (mean, 324 days) (P = 0.03). None of the four cats inoculated with B. koehlerae had bacteremia relapse. As shown by enzyme-linked immunosorbent assay (ELISA) using B. koehlerae outer membrane protein (OMP) antigens, the four cats developed a species-specific antibody response, and ELISA testing using other feline Bartonella OMP antigens showed statistically lower optical density values. All four cats developed similar antibody reactivity patterns to B. koehlerae OMP antigens as seen by Western blotting, each with at least 20 seroreactive protein bands. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, protein profile differences were observed for both whole-cell lysate and OMPs from B. koehlerae, compared with B. henselae and B. clarridgeiae. B. koehlerae was more closely related to B. henselae than to B. clarridgeiae by protein profile, and this relatedness was also confirmed by analysis of the genomic DNA profiles by pulsed-field gel electrophoresis.",,"['Yamamoto, Kazuhiro', 'Chomel, Bruno B.', 'Kasten, Rickie W.', 'Hew, Carrie M.', 'Weber, David K.', 'Lee, Wilson I.', 'Droz, Sara', 'Koehler, Jane E.']",,,,
,PMC,The Cytoplasmic Tail of Infectious Bronchitis Virus E Protein Directs Golgi Targeting,http://dx.doi.org/10.1128/JVI.76.3.1273-1284.2002,PMC135861,,,"We have previously shown that the E protein of the coronavirus infectious bronchitis virus (IBV) is localized to the Golgi complex when expressed exogenously from cDNA. Here, we report that neither the transmembrane domain nor the short lumenal domain of IBV E is required for Golgi targeting. However, an N-terminal truncation containing only the cytoplasmic domain (CTE) was efficiently localized to the Golgi complex, and this domain could retain a reporter protein in the Golgi. Thus, the cytoplasmic tail of the E protein is necessary and sufficient for Golgi targeting. The IBV E protein is palmitoylated on one or two cysteine residues adjacent to its transmembrane domain, but palmitoylation was not required for proper Golgi targeting. Using C-terminal truncations, we determined that the IBV E Golgi targeting information is present between tail amino acids 13 and 63. Upon treatment with brefeldin A, both the E and CTE proteins redistributed to punctate structures that colocalized with the Golgi matrix proteins GM130 and p115 instead of being localized to the endoplasmic reticulum like Golgi glycosylation enzymes. This suggests that IBV E is associated with the Golgi matrix through interactions of its cytoplasmic tail and may have interesting implications for coronavirus assembly in early Golgi compartments.",,"['Corse, Emily', 'Machamer, Carolyn E.']",,,,
,PMC,Soluble Receptor Potentiates Receptor-Independent Infection by Murine Coronavirus,http://dx.doi.org/10.1128/JVI.76.3.950-958.2002,PMC135807,,,"Mouse hepatitis virus (MHV) infection spreads from MHV-infected DBT cells, which express the MHV receptor CEACAM1 (MHVR), to BHK cells, which are devoid of the receptor, by intercellular membrane fusion (MHVR-independent fusion). This mode of infection is a property of wild-type (wt) JHMV cl-2 virus but is not seen in cultures infected with the mutant virus JHMV srr7. In this study, we show that soluble MHVR (soMHVR) potentiates MHVR-independent fusion in JHMV srr7-infected cultures. Thus, in the presence of soMHVR, JHMV srr7-infected DBT cells overlaid onto BHK cells induce BHK cell syncytia and the spread of JHMV srr7 infection. This does not occur in the absence of soMHVR. soMHVR also enhanced wt virus MHVR-independent fusion. These effects were dependent on the concentration of soMHVR in the culture and were specifically blocked by the anti-MHVR monoclonal antibody CC1. Together with these observations, direct binding of soMHVR to the virus spike (S) glycoprotein as revealed by coimmunoprecipitation demonstrated that the effect is mediated by the binding of soMHVR to the S protein. Furthermore, fusion of BHK cells expressing the JHMV srr7 S protein was also induced by soMHVR. These results indicated that the binding of soMHVR to the S protein expressed on the DBT cell surface potentiates the fusion of MHV-infected DBT cells with nonpermissive BHK cells. We conclude that the binding of soMHVR to the S protein converts the S protein to a fusion-active form competent to mediate cell-cell fusion, in a fashion similar to the fusion of virus and cell membranes.",,"['Taguchi, Fumihiro', 'Matsuyama, Shutoku']",,,,
,PMC,Heterologous Gene Expression from Transmissible Gastroenteritis Virus Replicon Particles,http://dx.doi.org/10.1128/JVI.76.3.1422-1434.2002,PMC135785,,,"We have recently isolated a transmissible gastroenteritis virus (TGEV) infectious construct designated TGEV 1000 (B. Yount, K. M. Curtis, and R. S. Baric, J. Virol. 74:10600–10611, 2000). Using this construct, a recombinant TGEV was constructed that replaced open reading frame (ORF) 3A with a heterologous gene encoding green fluorescent protein (GFP). Following transfection of baby hamster kidney (BHK) cells, a recombinant TGEV (TGEV-GFP2) was isolated that replicated efficiently and expressed GFP. Replicon constructs were constructed that lacked either the ORF 3B and E genes or the ORF 3B, E, and M genes [TGEV-Rep(AvrII) and TGEV-Rep(EcoNI), respectively]. As the E and M proteins are essential for TGEV virion budding, these replicon RNAs should replicate but not result in the production of infectious virus. Following cotransfection of BHK cells with the replicon RNAs carrying gfp, GFP expression was evident by fluorescent microscopy and leader-containing transcripts carrying gfp were detected by reverse transcription-PCR (RT-PCR). Subsequent passage of cell culture supernatants onto permissive swine testicular (ST) cells did not result in the virus, GFP expression, or the presence of leader-containing subgenomic transcripts, demonstrating the single-hit nature of the TGEV replicon RNAs. To prepare a packaging system to assemble TGEV replicon particles (TGEV VRP), the TGEV E gene was cloned into a Venezuelan equine encephalitis (VEE) replicon expression vector and VEE replicon particles encoding the TGEV E protein were isolated [VEE-TGEV(E)]. BHK cells were either cotransfected with TGEV-Rep(AvrII) (E gene deletion) and VEE-TGEV(E) RNA transcripts or transfected with TGEV-Rep(AvrII) RNA transcripts and subsequently infected with VEE VRPs carrying the TGEV E gene. In both cases, GFP expression and leader-containing GFP transcripts were detected in transfected cells. Cell culture supernatants, collected ∼36 h posttransfection, were passed onto fresh ST cells where GFP expression was evident ∼18 h postinfection. Leader-containing GFP transcripts containing the ORF 3B and E gene deletions were detected by RT-PCR. Recombinant TGEV was not released from these cultures. Under identical conditions, TGEV-GFP2 spread throughout ST cell cultures, expressed GFP, and formed viral plaques. The development of infectious TGEV replicon particles should assist studies of TGEV replication and assembly as well as facilitate the production of novel swine candidate vaccines.",,"['Curtis, Kristopher M.', 'Yount, Boyd', 'Baric, Ralph S.']",,,,
,PMC,Transcription Regulatory Sequences and mRNA Expression Levels in the Coronavirus Transmissible Gastroenteritis Virus,http://dx.doi.org/10.1128/JVI.76.3.1293-1308.2002,PMC135778,,,"The transcription regulatory sequences (TRSs) of the coronavirus transmissible gastroenteritis virus (TGEV) have been characterized by using a helper virus-dependent expression system based on coronavirus-derived minigenomes to study the synthesis of subgenomic mRNAs. The TRSs are located at the 5′ end of TGEV genes and include a highly conserved core sequence (CS), 5′-CUAAAC-3′, that is essential for mediating a 100- to 1,000-fold increase in mRNA synthesis when it is located in the appropriate context. The relevant sequences contributing to TRS activity have been studied by extending the CS 5′ upstream and 3′ downstream. Sequences from virus genes flanking the CS influenced transcription levels from moderate (10- to 20-fold variation) to complete mRNA synthesis silencing, as shown for a canonical CS at nucleotide (nt) 120 from the initiation codon of the S gene that did not lead to the production of the corresponding mRNA. An optimized TRS has been designed comprising 88 nt from the N gene TRS, the CS, and 3 nt 3′ to the M gene CS. Further extension of the 5′-flanking nucleotides (i.e., by 176 nt) decreased subgenomic RNA levels. The expression of a reporter gene (β-glucuronidase) by using the selected TRS led to the production of 2 to 8 μg of protein per 10(6) cells. The presence of an appropriate Kozak context led to a higher level of protein expression. Virus protein levels were shown to be dependent on transcription and translation regulation.",,"['Alonso, Sara', 'Izeta, Ander', 'Sola, Isabel', 'Enjuanes, Luis']",,,,
,PMC,"Extra-articular cartilage affected in collagen-induced, but not pristane-induced, arthritis models",http://dx.doi.org/10.1046/j.1365-2249.2002.01712.x,PMC1906294,,,"Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily affecting cartilaginous joints but also extra-articular tissues such as the nose and upper respiratory tract. We have investigated extra-articular cartilage involvement in two commonly used animal models for RA, collagen-induced and pristane-induced arthritis, by immunizing rats with different susceptibility to disease (LEW.1 A, LEW.1F and DA rats). We found that nasal and tracheolaryngeal cartilage is affected in LEW.1 A and DA rats to varying degrees in collagen-induced arthritis but not in any strain in the pristane-induced model. Antibodies to matrilin-1, a cartilage-specific protein expressed mainly in tracheolaryngeal and nasal cartilage but not in joints, were positively associated with the presence of inflammation in nasal cartilage. In contrast, no antibody response to matrilin-1 could be detected in pristane-induced arthritis. In addition, nasal vaccination with collagen type II prior to immunization in DA rats significantly decreased the antibody response to matrilin-1 at day 56, but not at earlier time points, indicating a late protective effect on extra-articular cartilage. We conclude that pristane-induced arthritis is a joint-specific model whereas collagen-induced arthritis affect joints as well as extra-articular cartilage. Furthermore, collagen immunization induces an antibody response to matrilin-1.",,"['Hansson, A-S', 'Lu, S', 'Holmdahl, R']",,,,
,PMC,The p23 Protein of Citrus Tristeza Virus Controls Asymmetrical RNA Accumulation,http://dx.doi.org/10.1128/JVI.76.2.473-483.2002,PMC136848,,,"Citrus tristeza virus (CTV), a member of the Closteroviridae, has a 19.3-kb positive-stranded RNA genome that is organized into 12 open reading frames (ORFs) with the 10 3′ genes expressed via a nested set of nine or ten 3′-coterminal subgenomic mRNAs (sgRNAs). Relatively large amounts of negative-stranded RNAs complementary to both genomic and sgRNAs accumulate in infected cells. As is characteristic of RNA viruses, wild-type CTV produced more positive than negative strands, with the plus-to-minus ratios of genomic and sgRNAs estimated at 10 to 20:1 and 40 to 50:1, respectively. However, a mutant with all of the 3′ genes deleted replicated efficiently, but produced plus to minus strands at a markedly decreased ratio of 1 to 2:1. Deletion analysis of 3′-end genes revealed that the p23 ORF was involved in asymmetric RNA accumulation. A mutation which caused a frameshift after the fifth codon resulted in nearly symmetrical RNA accumulation, suggesting that the p23 protein, not a cis-acting element within the p23 ORF, controls asymmetric accumulation of CTV RNAs. Further in-frame deletion mutations in the p23 ORF suggested that amino acid residues 46 to 180, which contained RNA-binding and zinc finger domains, were indispensable for asymmetrical RNA accumulation, while the N-terminal 5 to 45 and C-terminal 181 to 209 amino acid residues were not absolutely required. Mutation of conserved cysteine residues to alanines in the zinc finger domain resulted in loss of activity of the p23 protein, suggesting involvement of the zinc finger in asymmetric RNA accumulation. The absence of p23 gene function was manifested by substantial increases in accumulation of negative-stranded RNAs and only modest decreases in positive-stranded RNAs. Moreover, the substantial decrease in the accumulation of negative-stranded coat protein (CP) sgRNA in the presence of the functional p23 gene resulted in a 12- to 15-fold increase in the expression of the CP gene. Apparently the excess negative-stranded sgRNA reduces the availability of the corresponding positive-stranded sgRNA as a messenger. Thus, the p23 protein controls asymmetric accumulation of CTV RNAs by downregulating negative-stranded RNA accumulation and indirectly increases expression of 3′ genes.",,"['Satyanarayana, Tatineni', 'Gowda, Siddarame', 'Ayllón, María A.', 'Albiach-Martí, María R.', 'Rabindran, Shailaja', 'Dawson, William O.']",,,,
,PMC,VirOligo: a database of virus-specific oligonucleotides,,PMC99087,,,"VirOligo is a database of virus-specific oligonucleotides. The VirOligo database consists of two tables, Common data and Oligo data. The Oligo data table contains PCR primers and hybridization probes used for detection of viral nucleic acids and the Common data table contains the experimental conditions used in their detection. Each oligonucleotide entry contains links to PubMed, GenBank, NCBI Taxonomy databases and BLAST. As of July 2001, the VirOligo database contains a complete listing of oligonucleotides specific to viral agents associated with bovine respiratory disease that were published in English in peer-reviewed journals. The viruses are bovine herpes virus types 1, 3, 4 and 5, bovine viral diarrhea virus, bovine parainfluenza 3 virus, bovine respiratory syncytial virus, bovine adenovirus, bovine rhinovirus, bovine coronavirus, bovine reovirus, bovine enterovirus and alcelaphine herpesvirus-1. The VirOligo database is being expanded to other viruses and can be accessed through the Internet at http://viroligo.okstate.edu/.",,"['Onodera, Kenji', 'Melcher, Ulrich']",,,,
,PMC,The Brome mosaic virus subgenomic promoter hairpin is structurally similar to the iron-responsive element and functionally equivalent to the minus-strand core promoter stem-loop C.,,PMC1370233,,,"In the Bromoviridae family of plant viruses, trinucleotide hairpin loops play an important role in RNA transcription. Recently, we reported that Brome mosaic virus (BMV) subgenomic (sg) transcription depended on the formation of an unusual triloop hairpin. By native gel electrophoresis, enzymatic structure probing, and NMR spectroscopy it is shown here that in the absence of viral replicase the hexanucleotide loop 5'C1AUAG5A3' of this RNA structure can adopt a pseudo trinucleotide loop conformation by transloop base pairing between C1 and G5. By means of in vitro replication assays using partially purified BMV RNA-dependent RNA polymerase (RdRp) it was found that other base pairs contribute to sg transcription, probably by stabilizing the formation of this pseudo triloop, which is proposed to be the primary element recognized by the viral replicase. The BMV pseudo triloop structure strongly resembles iron-responsive elements (IREs) in cellular messenger RNAs and may represent a general protein-binding motif. In addition, in vitro replication assays showed that the BMV sg hairpin is functionally equivalent to the minus-strand core promoter hairpin stem-loop C at the 3' end of BMV RNAs. Replacement of the sg hairpin by stem-loop C yielded increased sg promoter activity whereas replacement of stem-loop C by the sg hairpin resulted in reduced minus-strand promoter activity. We conclude that AUA triloops represent the common motif in the BMV sg and minus-strand promoters required for recruitment of the viral replicase. Additional sequence elements of the minus-strand promoter are proposed to direct the RdRp to the initiation site at the 3' end of the genomic RNA.",,"['Joost Haasnoot, P C', 'Olsthoorn, René C L', 'Bol, John F']",,,,
,PMC,Influence of the stacking potential of the base 3' of tandem shift codons on -1 ribosomal frameshifting used for gene expression.,,PMC1370227,,,"Translating ribosomes can shift reading frame at specific sites with high efficiency for gene expression purposes. The most common type of shift to the -1 frame involves a tandem realignment of two anticodons from pairing with mRNA sequence of the form X XXY YYZ to XXX YYY Z where the spaces indicate the reading frame. The predominant -1 shift site of this type in eubacteria is A AAA AAG. The present work shows that in Escherichia coli the identity of the 6 nt 3' of this sequence can be responsible for a 14-fold variation in frameshift frequency. The first 3' nucleotide has the primary effect, with, in order of decreasing efficiency, U > C > A > G. This effect is independent of other stimulators of frameshifting. It is detected with other X XXA AAG sequences, but not with several other heptameric -1 shift sites. Pairing of E. coli tRNALYS with AAG is especially weak at the third codon position. We propose that strong stacking of purines 3' of AAG stabilizes pairing of tRNALys, diminishing the chance of codon:anticodon dissociation that is a prerequisite for the realignment involved in frameshifting.",,"['Bertrand, Claire', 'Prère, Marie Françoise', 'Gesteland, Raymond F', 'Atkins, John F', 'Fayet, Olivier']",,,,
,PMC,A flu optical immunoassay (ThermoBioStar's FLU OIA): a diagnostic tool for improved influenza management.,http://dx.doi.org/10.1098/rstb.2001.1005,PMC1088569,,,"ThermoBioStar's and Biota's flu optical immunoassay (FLU OIA) is a rapid test designed to diagnose influenza A and B infection using a variety of specimen types. The assay uses highly sensitive thin-film detection methods, coupled with specific monoclonal antibodies to the nucleoprotein. The test is simple to perform, requires no instrumentation and is intended to provide a result within 15 min of test initiation in the 'point-of-care' environment. In initial clinical studies, the assay was demonstrated to be equivalent to culture in identifying infected individuals. Subsequent independent studies using a variety of sample types have demonstrated sensitivity ranging from 48 to 100% and specificities ranging from 93 to 97%. In addition to detecting human strains, this assay has been demonstrated to be capable of detecting a variety of avian and non-human mammalian influenza viruses. The FLU OIA test has been used in large-scale surveillance schemes intended to provide rapid epidemiological data during normal influenza seasons and has demonstrated the potential for fulfilling a similar role for multispecies surveillance in, for example, conditions that offer challenges for conventional virus isolation methods. Conceivably, such use should facilitate the timely recognition of influenza outbreaks and prioritization of positive specimens for more conventional, laboratory characterization, leading to improved interpandemic surveillance and rapid reaction in the face of the next pandemic.",,"['Tucker, S P', 'Cox, C', 'Steaffens, J']",,,,
,PMC,Sequence requirements for RNA strand transfer during nidovirus discontinuous subgenomic RNA synthesis,http://dx.doi.org/10.1093/emboj/20.24.7220,PMC125340,,,"Nidovirus subgenomic mRNAs contain a leader sequence derived from the 5′ end of the genome fused to different sequences (‘bodies’) derived from the 3′ end. Their generation involves a unique mechanism of discontinuous subgenomic RNA synthesis that resembles copy-choice RNA recombination. During this process, the nascent RNA strand is transferred from one site in the template to another, during either plus or minus strand synthesis, to yield subgenomic RNA molecules. Central to this process are transcription-regulating sequences (TRSs), which are present at both template sites and ensure the fidelity of strand transfer. Here we present results of a comprehensive co-variation mutagenesis study of equine arteritis virus TRSs, demonstrating that discontinuous RNA synthesis depends not only on base pairing between sense leader TRS and antisense body TRS, but also on the primary sequence of the body TRS. While the leader TRS merely plays a targeting role for strand transfer, the body TRS fulfils multiple functions. The sequences of mRNA leader–body junctions of TRS mutants strongly suggested that the discontinuous step occurs during minus strand synthesis.",,"['Pasternak, Alexander O.', 'van den Born, Erwin', 'Spaan, Willy J.M.', 'Snijder, Eric J.']",,,,
,PMC,A retrospective study of neonatal mortality in farmed elk.,,PMC1476682,,,"Despite the increasing importance of the Canadian elk industry, the veterinary literature concerning diseases of elk is sparse, in particular for the neonatal period. This study summarizes necropsy findings in 111 farmed elk calves, up to 30 days of age, submitted to the diagnostic laboratory of the Western College of Veterinary Medicine over a 9-year period (990 to 1998). Causes of mortality fit into 3 categories: infectious disease, noninfectious disease, and undetermined. Organisms causing disease included Escherichia coli, Listeria monocytogenes, and Cryptosporidium sp. Starvation, including dehydration, was also a significant cause of mortality. Necropsy records are a useful source of information, but their scope is limited. There is a need for research that determines the prevalence of neonatal elk diseases and identifies risk factors for morbidity and mortality.",,"['Pople, N C', 'Allen, A L', 'Woodbury, M R']",,,,
,PMC,Evaluation of Cholera Vaccines Formulated with Toxin-Coregulated Pilin Peptide Plus Polymer Adjuvant in Mice,http://dx.doi.org/10.1128/IAI.69.12.7695-7702.2001,PMC98864,,,"Cholera is an acute diarrheal disease that is caused by the gram-negative bacterium Vibrio cholerae. The low efficacy of currently available killed-whole-cell vaccines and the reactinogenicity coupled with potential reversion of live vaccines have thus far precluded widespread vaccination for the control of cholera. Recent studies on the molecular nature of the virulence components that contribute to V. cholerae pathogenesis have provided insights into possible approaches for the development of a defined subunit cholera vaccine. Genetic analysis has demonstrated that the toxin-coregulated pilus (TCP) is the major factor that contributes to colonization of the human intestine by V. cholerae. In addition, polyclonal and several monoclonal antibodies directed against TCP have been shown to provide passive immunity to disease in the infant mouse cholera model. In the present study, synthetic peptides corresponding to portions of the C-terminal disulfide region of TcpA pilin were formulated with polymer adjuvants currently in clinical trials and used to actively immunize adult female CD-1 mice. The experimental vaccine formulations elicited high levels of antigen-specific immunoglobulin G (IgG), including a broad spectrum of subclasses (IgG1, IgG2a, IgG2b, and IgG3), and lower levels of IgA. Infant mice born to the immunized mothers showed 100% protection against a 50% lethal dose (1 LD(50)) challenge and 50% protection against a 10-LD(50) challenge with virulent strain O395. These results indicate that specific regions of TcpA, including those delineated by the peptides used in this study, have the potential to be incorporated into an effective defined subunit vaccine for cholera.",,"['Wu, Jia-Yan', 'Wade, William F.', 'Taylor, Ronald K.']",,,,
,PMC,Reverse Genetics System for the Avian Coronavirus Infectious Bronchitis Virus,http://dx.doi.org/10.1128/JVI.75.24.12359-12369.2001,PMC116132,,,"Major advances in the study of the molecular biology of RNA viruses have resulted from the ability to generate and manipulate full-length genomic cDNAs of the viral genomes with the subsequent synthesis of infectious RNA for the generation of recombinant viruses. Coronaviruses have the largest RNA virus genomes and, together with genetic instability of some cDNA sequences in Escherichia coli, this has hampered the generation of a reverse-genetics system for this group of viruses. In this report, we describe the assembly of a full-length cDNA from the positive-sense genomic RNA of the avian coronavirus, infectious bronchitis virus (IBV), an important poultry pathogen. The IBV genomic cDNA was assembled immediately downstream of a T7 RNA polymerase promoter by in vitro ligation and cloned directly into the vaccinia virus genome. Infectious IBV RNA was generated in situ after the transfection of restricted recombinant vaccinia virus DNA into primary chick kidney cells previously infected with a recombinant fowlpox virus expressing T7 RNA polymerase. Recombinant IBV, containing two marker mutations, was recovered from the transfected cells. These results describe a reverse-genetics system for studying the molecular biology of IBV and establish a paradigm for generating genetically defined vaccines for IBV.",,"['Casais, Rosa', 'Thiel, Volker', 'Siddell, Stuart G.', 'Cavanagh, David', 'Britton, Paul']",,,,
,PMC,Organization of Two Transmissible Gastroenteritis Coronavirus Membrane Protein Topologies within the Virion and Core,http://dx.doi.org/10.1128/JVI.75.24.12228-12240.2001,PMC116120,,,"The difference in membrane (M) protein compositions between the transmissible gastroenteritis coronavirus (TGEV) virion and the core has been studied. The TGEV M protein adopts two topologies in the virus envelope, a Nexo-Cendo topology (with the amino terminus exposed to the virus surface and the carboxy terminus inside the virus particle) and a Nexo-Cexo topology (with both the amino and carboxy termini exposed to the virion surface). The existence of a population of M molecules adopting a Nexo-Cexo topology in the virion envelope was demonstrated by (i) immunopurification of (35)S-labeled TGEV virions using monoclonal antibodies (MAbs) specific for the M protein carboxy terminus (this immunopurification was inhibited only by deletion mutant M proteins that maintained an intact carboxy terminus), (ii) direct binding of M-specific MAbs to the virus surface, and (iii) mass spectrometry analysis of peptides released from trypsin-treated virions. Two-thirds of the total number of M protein molecules found in the virion were associated with the cores, and one-third was lost during core purification. MAbs specific for the M protein carboxy terminus were bound to native virions through the M protein in a Nexo-Cexo conformation, and these molecules were removed when the virus envelope was disrupted with NP-40 during virus core purification. All of the M protein was susceptible to N-glycosidase F treatment of the native virions, which indicates that all the M protein molecules are exposed to the virus surface. Cores purified from glycosidase-treated virions included M protein molecules that completely or partially lost the carbohydrate moiety, which strongly suggests that the M protein found in the cores was also exposed in the virus envelope and was not present exclusively in the virus interior. A TGEV virion structure integrating all the data is proposed. According to this working model, the TGEV virion consists of an internal core, made of the nucleocapsid and the carboxy terminus of the M protein, and the envelope, containing the spike (S) protein, the envelope (E) protein, and the M protein in two conformations. The two-thirds of the molecules that are in a Nexo-Cendo conformation (with their carboxy termini embedded within the virus core) interact with the internal core, and the remaining third of the molecules, whose carboxy termini are in a Nexo-Cexo conformation, are lost during virus core purification.",,"['Escors, David', 'Camafeita, Emilio', 'Ortego, Javier', 'Laude, Hubert', 'Enjuanes, Luis']",,,,
,PMC,Secondary Structural Elements within the 3′ Untranslated Region of Mouse Hepatitis Virus Strain JHM Genomic RNA,http://dx.doi.org/10.1128/JVI.75.24.12105-12113.2001,PMC116106,,,"Previously, we characterized two host protein binding elements located within the 3′-terminal 166 nucleotides of the mouse hepatitis virus (MHV) genome and assessed their functions in defective-interfering (DI) RNA replication. To determine the role of RNA secondary structures within these two host protein binding elements in viral replication, we explored the secondary structure of the 3′-terminal 166 nucleotides of the MHV strain JHM genome using limited RNase digestion assays. Our data indicate that multiple stem-loop and hairpin-loop structures exist within this region. Mutant and wild-type DIssEs were employed to test the function of secondary structure elements in DI RNA replication. Three stem structures were chosen as targets for the introduction of transversion mutations designed to destroy base pairing structures. Mutations predicted to destroy the base pairing of nucleotides 142 to 136 with nucleotides 68 to 74 exhibited a deleterious effect on DIssE replication. Destruction of base pairing between positions 96 to 99 and 116 to 113 also decreased DI RNA replication. Mutations interfering with the pairing of nucleotides 67 to 63 with nucleotides 52 to 56 had only minor effects on DIssE replication. The introduction of second complementary mutations which restored the predicted base pairing of positions 142 to 136 with 68 to 74 and nucleotides 96 to 99 with 116 to 113 largely ameliorated defects in replication ability, restoring DI RNA replication to levels comparable to that of wild-type DIssE RNA, suggesting that these secondary structures are important for efficient MHV replication. We also identified a conserved 23-nucleotide stem-loop structure involving nucleotides 142 to 132 and nucleotides 68 to 79. The upstream side of this conserved stem-loop is contained within a host protein binding element (nucleotides 166 to 129).",,"['Liu, Qi', 'Johnson, Reed F.', 'Leibowitz, Julian L.']",,,,
,PMC,SJL/J Mice Are Highly Susceptible to Infection by  Mouse Adenovirus Type 1,http://dx.doi.org/10.1128/JVI.75.24.12039-12046.2001,PMC116099,,,"Mouse adenovirus type 1 (MAV-1) targets endothelial and monocyte/macrophage cells throughout the mouse. Depending on the strain of mouse and dose or strain of virus, infected mice may survive, become persistently infected, or die. We surveyed inbred mouse strains and found that for the majority tested the 50% lethal doses (LD(50)s) were >10(4.4) PFU. However, SJL/J mice were highly susceptible to MAV-1, with a mean LD(50) of 10(−0.32) PFU. Infected C3H/HeJ (resistant) and SJL/J (susceptible) mice showed only modest differences in histopathology. Susceptible mice had significantly higher viral loads in the brain and spleen at 8 days postinfection than resistant mice. Infection of primary macrophages or mouse embryo fibroblasts from SJL/J and C3H/HeJ mice gave equivalent yields of virus, suggesting that a receptor difference between strains is not responsible for the susceptibility difference. When C3H/HeJ mice were subjected to sublethal doses of gamma irradiation, they became susceptible to MAV-1, with an LD(50) like that of SJL/J mice. Antiviral immunoglobulin G (IgG) levels were measured in susceptible and resistant mice infected by an early region 1A null mutant virus that is less virulent that wild-type virus. The antiviral IgG levels were high and similar in the two strains of mice. Taken together, these results suggest that immune response differences may in part account for differences in susceptibility to MAV-1 infection.",,"['Spindler, Katherine R.', 'Fang, Lei', 'Moore, Martin L.', 'Hirsch, Gwen N.', 'Brown, Corrie C.', 'Kajon, Adriana']",,,,
,PMC,"Molecular Determinants of Virulence, Cell Tropism, and Pathogenic Phenotype of Infectious Bursal Disease Virus",http://dx.doi.org/10.1128/JVI.75.24.11974-11982.2001,PMC116092,,,"Infectious bursal disease viruses (IBDVs), belonging to the family Birnaviridae, exhibit a wide range of immunosuppressive potential, pathogenicity, and virulence for chickens. The genomic segment A encodes all the structural (VP2, VP4, and VP3) and nonstructural proteins, whereas segment B encodes the viral RNA-dependent RNA polymerase (VP1). To identify the molecular determinants for the virulence, pathogenic phenotype, and cell tropism of IBDV, we prepared full-length cDNA clones of a virulent strain, Irwin Moulthrop (IM), and constructed several chimeric cDNA clones of segments A and B between the attenuated vaccine strain (D78) and the virulent IM or GLS variant strain. Using the cRNA-based reverse-genetics system developed for IBDV, we generated five chimeric viruses after transfection by electroporation procedures in Vero or chicken embryo fibroblast (CEF) cells, one of which was recovered after propagation in embryonated eggs. To evaluate the characteristics of the recovered viruses in vivo, we inoculated 3-week-old chickens with D78, IM, GLS, or chimeric viruses and analyzed their bursae for pathological lesions 3 days postinfection. Viruses in which VP4, VP4-VP3, and VP1 coding sequences of the virulent strain IM were substituted for the corresponding region in the vaccine strain failed to induce hemorrhagic lesions in the bursa. In contrast, viruses in which the VP2 coding region of the vaccine strain was replaced with the variant GLS or virulent IM strain caused rapid bursal atrophy or hemorrhagic lesions in the bursa, as seen with the variant or classical virulent strain, respectively. These results show that the virulence and pathogenic-phenotype markers of IBDV reside in VP2. Moreover, one of the chimeric viruses containing VP2 sequences of the virulent strain could not be recovered in Vero or CEF cells but was recovered in embryonated eggs, suggesting that VP2 contains the determinants for cell tropism. Similarly, one of the chimeric viruses containing the VP1 segment of the virulent strain could not be recovered in Vero cells but was recovered in CEF cells, suggesting that VP1 contains the determinants for cell-specific replication in Vero cells. By comparing the deduced amino acid sequences of the D78 and IM strains and their reactivities with monoclonal antibody 21, which binds specifically to virulent IBDV, the putative amino acids involved in virulence and cell tropism were identified. Our results indicate that residues Gln at position 253 (Gln253), Asp279, and Ala284 of VP2 are involved in the virulence, cell tropism, and pathogenic phenotype of virulent IBDV.",,"['Brandt, Meggin', 'Yao, Kun', 'Liu, Meihong', 'Heckert, Robert A.', 'Vakharia, Vikram N.']",,,,
,PMC,Ribosomal Pausing at a Frameshifter RNA Pseudoknot Is Sensitive to Reading Phase but Shows Little Correlation with Frameshift Efficiency,http://dx.doi.org/10.1128/MCB.21.24.8657-8670.2001,PMC100026,,,"Here we investigated ribosomal pausing at sites of programmed −1 ribosomal frameshifting, using translational elongation and ribosome heelprint assays. The site of pausing at the frameshift signal of infectious bronchitis virus (IBV) was determined and was consistent with an RNA pseudoknot-induced pause that placed the ribosomal P- and A-sites over the slippery sequence. Similarly, pausing at the simian retrovirus 1 gag/pol signal, which contains a different kind of frameshifter pseudoknot, also placed the ribosome over the slippery sequence, supporting a role for pausing in frameshifting. However, a simple correlation between pausing and frameshifting was lacking. Firstly, a stem-loop structure closely related to the IBV pseudoknot, although unable to stimulate efficient frameshifting, paused ribosomes to a similar extent and at the same place on the mRNA as a parental pseudoknot. Secondly, an identical pausing pattern was induced by two pseudoknots differing only by a single loop 2 nucleotide yet with different functionalities in frameshifting. The final observation arose from an assessment of the impact of reading phase on pausing. Given that ribosomes advance in triplet fashion, we tested whether the reading frame in which ribosomes encounter an RNA structure (the reading phase) would influence pausing. We found that the reading phase did influence pausing but unexpectedly, the mRNA with the pseudoknot in the phase which gave the least pausing was found to promote frameshifting more efficiently than the other variants. Overall, these experiments support the view that pausing alone is insufficient to mediate frameshifting and additional events are required. The phase dependence of pausing may be indicative of an activity in the ribosome that requires an optimal contact with mRNA secondary structures for efficient unwinding.",,"['Kontos, Harry', 'Napthine, Sawsan', 'Brierley, Ian']",,,,
,PMC,Evaluation of Two Enzyme-Linked Immunosorbent Assays for Detecting Salmonella enterica subsp. enterica Serovar Dublin  Antibodies in Bulk Milk,http://dx.doi.org/10.1128/CDLI.8.6.1049-1055.2001,PMC96224,,,"Two enzyme-linked immunosorbent assays (ELISAs) for the detecting Salmonella enterica subsp. enterica serovar Dublin antibodies in bulk milk were developed and evaluated for potential use in control programs. The ELISAs were based on either lipopolysacharide (LPS ELISA) or flagellar antigen (GP ELISA). Sensitivity was determined with 79 case herds with a wide range of clinical signs. Specificity was determined with 125 Dutch and 200 Swedish control herds. The relation between antibodies in bulk milk, antibodies in serum, and the level of milk production of individual cows was studied with 61 case herds. The optimal optical density (OD) values of the LPS ELISA and the GP ELISA were determined to be 0.2 and 0.5, respectively. The sensitivities of the LPS ELISA and the GP ELISA were 54 and 63%, respectively, with a specificity of 98% for both ELISAs with samples from the Dutch control herds. The specificities for samples from the Swedish herds were 100% for the LPS ELISA and 95% for the GP ELISA. The sensitivity of the combination of tests was 65% when samples were run in parallel, and the specificity was 100% when samples were run in series, irrespective of whether the samples came from Dutch or Swedish control herds. The variance (R(2)) in the OD value for bulk milk samples could be explained by the percentage of seropositive lactating cows in a herd with the LPS ELISA for 51% of the samples and with the GP ELISA for 72%. The variance in the OD value was best explained by the combination of the percentage of seropositive lactating cows in the herd and the mean log(10) serum antibody titer for that herd (R(2) = 62% for the LPS ELISA and R(2) = 75% for the GP ELISA). Case herds more often tested negative by the ELISA with bulk milk when the percentage of seropositive lactating cows was less than 5%. It is concluded that both ELISAs with bulk milk can be used in control programs to distinguish between infected and noninfected herds. Specificity can be increased by using the two tests in combination. Sensitivity was relatively low for both single tests and both tests combined.",,"['Veling, J.', 'van Zijderveld, F. G.', 'van Zijderveld-van Bemmel, A. M.', 'Schukken, Y. H.', 'Barkema, H. W.']",,,,
,PMC,Fv-4: Identification of the Defect in Env and the Mechanism of Resistance to Ecotropic Murine Leukemia Virus,http://dx.doi.org/10.1128/JVI.75.22.11244-11248.2001,PMC114706,,,"Mice expressing the Fv-4 gene are resistant to infection by ecotropic murine leukemia viruses (MuLVs). The Fv-4 gene encodes an envelope (Env) protein whose putative receptor-binding domain resembles that of ecotropic MuLV Env protein. Resistance to ecotropic MuLVs appears to result from viral interference involving binding of the endogenously expressed Fv-4 env-encoded protein to the ecotropic receptor, although the immune system also plays a role in resistance. The Fv-4 env-encoded protein is processed normally and can be incorporated into virus particles but is unable to promote viral entry. Among the many sequence variations between the transmembrane (TM) subunit of the Fv-4 env-encoded protein and the TM subunits of other MuLV Env proteins, there is a substitution of an arginine residue in the Fv-4 env-encoded protein for a glycine residue (gly-491 in Moloney MuLV Env) that is otherwise conserved in all of the other MuLVs. This residue is present in the MuLV TM fusion peptide sequence. In this study, gly-491 of Moloney MuLV Env has been replaced with other residues and a mutant Env bearing a substitution for gly-487 was also created. G491R recapitulates the Fv-4 Env phenotype in cell culture, indicating that this substitution is sufficient for creation of an Env protein that can establish the interference-mediated resistance to ecotropic viruses produced by the Fv-4 gene. Analysis of the mutant MuLV Env proteins also has implications for an understanding of the role of conserved glycine residues in fusion peptides and for the engineering of organismal resistance to retroviruses.",,"['Taylor, Gwen M.', 'Gao, Yi', 'Sanders, David Avram']",,,,
,PMC,Poliovirus 5′-Terminal Cloverleaf RNA Is Required in cis for VPg Uridylylation and the Initiation of Negative-Strand RNA Synthesis,http://dx.doi.org/10.1128/JVI.75.22.10696-10708.2001,PMC114651,,,"Chimeric poliovirus RNAs, possessing the 5′ nontranslated region (NTR) of hepatitis C virus in place of the 5′ NTR of poliovirus, were used to examine the role of the poliovirus 5′ NTR in viral replication. The chimeric viral RNAs were incubated in cell-free reaction mixtures capable of supporting the sequential translation and replication of poliovirus RNA. Using preinitiation RNA replication complexes formed in these reactions, we demonstrated that the 3′ NTR of poliovirus RNA was insufficient, by itself, to recruit the viral replication proteins required for negative-strand RNA synthesis. The 5′-terminal cloverleaf of poliovirus RNA was required in cis to form functional preinitiation RNA replication complexes capable of uridylylating VPg and initiating the synthesis of negative-strand RNA. These results are consistent with a model in which the 5′-terminal cloverleaf and 3′ NTRs of poliovirus RNA interact via temporally dynamic ribonucleoprotein complexes to coordinately mediate and regulate the sequential translation and replication of poliovirus RNA.",,"['Lyons, Traci', 'Murray, Kenneth E.', 'Roberts, Allan W.', 'Barton, David J.']",,,,
,PMC,Structural Analysis of the −1 Ribosomal Frameshift  Elements in Giardiavirus mRNA,http://dx.doi.org/10.1128/JVI.75.22.10612-10622.2001,PMC114643,,,"The RNA polymerase of giardiavirus (GLV) is synthesized as a fusion protein through a −1 ribosomal frameshift in a region where gag and pol open reading frames (ORFs) overlap. A heptamer, CCCUUUA, and a potential pseudoknot found in the overlap were predicted to be required for the frameshift. A 68-nucleotide (nt) cDNA fragment containing these elements was inserted between the GLV 5′ 631-nt cDNA and the out-of-frame luciferase gene that required a −1 frameshift within the 68-nt fragment for expression. Giardia lamblia trophozoites transfected with the transcript of this construct showed a frameshift frequency at 1.7%, coinciding with the polymerase-to-capsid protein ratio in GLV. The heptamer is required for the frameshift but can be replaced with other sequences of the same motif. Mutations placing stop codons in the 0 or −1 frame, located directly before or after the heptamer, implicated the latter as the site for the −1 frameshift. Shortening or destroying the putative stem decreased the frameshift efficiency threefold; the efficiency was fully recovered by mutations to restore the stem. Deleting 18 nt from the 3′ end of the 68-nt fragment, which formed the second stem in the putative pseudoknot, had no effect on the frequency of the frameshift. Chemical probing of the RNA secondary structure in the frameshift region showed that bases resistant to chemical modification were clustered in the putative stem structures, thus confirming the presence of the postulated stem-loop, while all the bases in the loop were chemically modified, thus ruling out their capability of forming a pseudoknot. These results confirmed the conclusion based on data from the mutation study that there is but a simple stem-loop downstream from the heptamer. Together, they constitute the structural elements for a −1 ribosomal frameshift in the GLV transcript.",,"['Li, Lei', 'Wang, Alice L.', 'Wang, Ching C.']",,,,
,PMC,CD8(+) T Lymphocytes Mediate Borna Disease Virus-Induced Immunopathology Independently of Perforin,http://dx.doi.org/10.1128/JVI.75.21.10460-10466.2001,PMC114620,,,"Perforin-mediated lysis of target cells is the major antiviral effector mechanism of CD8(+) T lymphocytes. We have analyzed the role of perforin in a mouse model for CD8(+) T-cell-mediated central nervous system (CNS) immunopathology induced by Borna disease virus. When a defective perforin gene was introduced into the genetic background of the Borna disease-susceptible mouse strain MRL, the resulting perforin-deficient mice developed strong neurological disease in response to infection indistinguishable from that of their perforin-expressing littermates. The onset of disease was slightly delayed. Brains of diseased perforin-deficient mice showed similar amounts and a similar distribution of CD8(+) T cells as wild-type animals. Perforin deficiency had no impact on the kinetics of viral spread through the CNS. Unlike brain lymphocytes from diseased wild-type mice, lymphocytes from perforin-deficient MRL mice showed no in vitro cytolytic activity towards target cells expressing the nucleoprotein of Borna disease virus. Taken together, these results demonstrate that CD8(+) T cells mediate Borna disease independent of perforin. They further suggest that the pathogenic potential of CNS-infiltrating CD8(+) T cells does not primarily reside in their lytic activity but rather in other functions.",,"['Hausmann, Jürgen', 'Schamel, Karin', 'Staeheli, Peter']",,,,
,PMC,Hemagglutinin 1-Specific Immunoglobulin G and Fab Molecules Mediate Postattachment Neutralization of Influenza A Virus by Inhibition of an Early Fusion Event,http://dx.doi.org/10.1128/JVI.75.21.10208-10218.2001,PMC114595,,,"In standard neutralization (STAN), virus and antibody are reacted together before inoculation of target cells, and inhibition of almost any of the processes concerned in the early interaction of virus and cell, including inhibition of virus attachment to cell receptors, can be the cause of neutralization by a particular monoclonal antibody (MAb). To simplify the interpretation of antibody action, we carried out a study of postattachment neutralization (PAN), where virus is allowed to attach to target cells before neutralizing antibody is introduced. We used influenza virus A/PR/8/34 (H1N1) and monoclonal immunoglobulin G (IgG) molecules and their Fabs specific to antigenic sites Sb (tip), Ca2 (loop), and Cb (hinge) of the hemagglutinin 1 (HA1) protein. All IgGs and Fabs gave PAN, although with reduced efficiency compared with STAN. Thus, bivalent binding of antibody was not essential for PAN. By definition, none of these MAbs gave PAN by inhibiting virus attachment, and they did not elute attached virus from the target cell or inhibit endocytosis of virus. However, virus-cell fusion, as demonstrated by R18 fluorescence dequenching or hemolysis of red blood cells, was inhibited in direct proportion to neutralization and in a dose-dependent manner and was thus likely to be responsible for the observed neutralization. However, to get PAN, it was necessary to inhibit the activation of the prefusion intermediate, the earliest known form on the fusion pathway that is created when virus is incubated at pH 5 and 4°C. PAN antibodies may act by binding HA trimers in contact with the cell and/or trimers in the immediate vicinity of the virus-cell contact point and so inhibit the recruitment of additional receptor-HA complexes.",,"['Edwards, M. J.', 'Dimmock, N. J.']",,,,
,PMC,Glycoprotein D-Independent Infectivity of Pseudorabies Virus Results in an Alteration of In Vivo Host Range and Correlates  with Mutations in Glycoproteins B and H,http://dx.doi.org/10.1128/JVI.75.21.10054-10064.2001,PMC114580,,,"Infection of cells by herpesviruses is initiated by the interaction of viral envelope glycoproteins with cellular receptors. In the alphaherpesvirus pseudorabies virus (PrV), the causative agent of Aujeszky's disease in pigs, the essential glycoprotein D (gD) mediates secondary attachment of virions to target cells by binding to newly identified cellular receptors (R. J. Geraghty, C. Krummenacher, G. H. Cohen, R. J. Eisenberg, and P. G. Spear, Science 280:1618–1620, 1998). However, in the presence of compensatory mutations, infection can also occur in the absence of gD, as evidenced by the isolation in cell culture of an infectious gD-negative PrV mutant (PrV-gD(−) Pass) (J. Schmidt, B. G. Klupp, A. Karger, and T. C. Mettenleiter, J. Virol. 71:17–24, 1997). PrV-gD(−) Pass is replication competent with an only moderate reduction in specific infectivity but appears to bind to receptors different from those recognized by wild-type PrV (A. Karger, J. Schmidt, and T. C. Mettenleiter, J. Virol. 72:7341–7348, 1998). To analyze whether this alteration in receptor usage in vitro influences infection in vivo, the model host mouse and the natural host pig were intranasally infected with PrV-gD(−) Pass and were compared to animals infected by wild-type PrV. For mice, a comparable progress of disease was observed, and all animals infected with mutant virus died, although they exhibited a slight delay in the onset of symptoms and, correspondingly, a longer time to death. In contrast, whereas wild-type PrV-infected pigs showed clinical signs and histological and histopathological findings typical of PrV infection, no signs of disease were observed after infection with PrV-gD(−) Pass. Moreover, in these animals, virus-infected cells were not detectable by immunohistochemical staining of different organ samples and no virus could be isolated from nasal swabs. Mutations in glycoproteins B and H were found to correlate with, and probably contribute to, gD-independent infectivity. In conclusion, although PrV-gD(−) Pass is virulent in mice, it is apparently unable to infect the natural host, the pig. This altered host range in vivo correlates with a difference of receptor usage in vitro and demonstrates for the first time the importance of gD receptors in alphaherpesvirus infection of an animal host.",,"['Schmidt, Jerg', 'Gerdts, Volker', 'Beyer, Jörg', 'Klupp, Barbara G.', 'Mettenleiter, Thomas C.']",,,,
,PMC,A Well-Connected and Conserved Nucleoplasmic Helicase Is Required for Production of Box C/D and H/ACA snoRNAs and Localization of snoRNP Proteins,http://dx.doi.org/10.1128/MCB.21.22.7731-7746.2001,PMC99944,,,"Biogenesis of small nucleolar RNA-protein complexes (snoRNPs) consists of synthesis of the snoRNA and protein components, snoRNP assembly, and localization to the nucleolus. Recently, two nucleoplasmic proteins from mice were observed to bind to a model box C/D snoRNA in vitro, suggesting that they function at an early stage in snoRNP biogenesis. Both proteins have been described in other contexts. The proteins, called p50 and p55 in the snoRNA binding study, are highly conserved and related to each other. Both have Walker A and B motifs characteristic of ATP- and GTP-binding and nucleoside triphosphate-hydrolyzing domains, and the mammalian orthologs have DNA helicase activity in vitro. Here, we report that the Saccharomyces cerevisiae ortholog of p50 (Rvb2, Tih2p, and other names) is required for production of C/D snoRNAs in vivo and, surprisingly, H/ACA snoRNAs as well. Point mutations in the Walker A and B motifs cause temperature-sensitive or lethal growth phenotypes and severe defects in snoRNA accumulation. Notably, depletion of p50 (called Rvb2 in this study) also impairs localization of C/D and H/ACA core snoRNP proteins Nop1p and Gar1p, suggesting a defect(s) in snoRNP assembly or trafficking to the nucleolus. Findings from other studies link Rvb2 orthologs with chromatin remodeling and transcription. Taken together, the present results indicate that Rvb2 is involved in an early stage of snoRNP biogenesis and may play a role in coupling snoRNA synthesis with snoRNP assembly and localization.",,"['King, Thomas H.', 'Decatur, Wayne A.', 'Bertrand, Edouard', 'Maxwell, E. Stuart', 'Fournier, Maurille J.']",,,,
,PMC,Cis-acting RNA elements at the 5' end of Sindbis virus genome RNA regulate minus- and plus-strand RNA synthesis.,,PMC1370205,,,"Alphavirus genome replication is a multistep asymmetric process. Several lines of evidence suggest that the template preference of the RNA replicase is regulated by proteolytic cleavage of the viral nonstructural polyprotein. Cis-acting RNA elements in the viral genome also play crucial roles in regulating genome replication and subgenomic RNA transcription. In this report, a series of RNA templates were analyzed in vitro and in vivo to define functional elements in the 5' end of the genome. The 5' UTR was shown to contain distinct core promoter elements for both minus- and plus-strand synthesis. In addition, two conserved stem-loop structures within the nsP1 coding sequence enhanced RNA replication but were not required. Studies with chimeric templates and trans-competition experiments suggest that the 5' determinant for minus-strand initiation can differ among alphaviruses and binds to one or more limiting replicase components. The results provide compelling evidence that the 5' and 3' ends of alphavirus genome RNAs must interact to initiate replication and we propose one model for how this interaction might occur. In addition to providing new insight into the initiation of alphavirus genome replication, these results have implications for the development of improved alphavirus vector systems with reduced recombination potential.",,"['Frolov, I', 'Hardy, R', 'Rice, C M']",,,,
,PMC,In Vivo Expression of Major Histocompatibility Complex Molecules on Oligodendrocytes and Neurons during Viral Infection,,PMC1850521,,,"Demyelination in multiple sclerosis and in animal models is associated with infiltrating CD8+ and CD4+ T cells. Although oligodendrocytes and axons are damaged in these diseases, the roles T cells play in the demyelination process are not completely understood. Antigen-specific CD8+ T cell lysis of target cells is dependent on interactions between the T cell receptor and major histocompatibility complex (MHC) class I-peptide complexes on the target cell. In the normal central nervous system, expression of MHC molecules is very low but often increases during inflammation. We set out to precisely define which central nervous system cells express MHC molecules in vivo during infection with a strain of murine hepatitis virus that causes a chronic, inflammatory demyelinating disease. Using double immunofluorescence labeling, we show that during acute infection with murine hepatitis virus, MHC class I is expressed in vivo by oligodendrocytes, neurons, microglia, and endothelia, and MHC class II is expressed only by microglia. These data indicate that oligodendrocytes and neurons have the potential to present antigen to T cells and thus be damaged by direct antigen-specific interactions with CD8+ T lymphocytes.",,"['Redwine, Jeffrey M.', 'Buchmeier, Michael J.', 'Evans, Claire F.']",,,,
,PMC,Direct Activation of Innate and Antigen-Presenting Functions of Microglia following Infection with Theiler's Virus,http://dx.doi.org/10.1128/JVI.75.20.9780-9789.2001,PMC114550,,,"Microglia are resident central nervous system (CNS) macrophages. Theiler's murine encephalomyelitis virus (TMEV) infection of SJL/J mice causes persistent infection of CNS microglia, leading to the development of a chronic-progressive CD4(+) T-cell-mediated autoimmune demyelinating disease. We asked if TMEV infection of microglia activates their innate immune functions and/or activates their ability to serve as antigen-presenting cells for activation of T-cell responses to virus and endogenous myelin epitopes. The results indicate that microglia lines can be persistently infected with TMEV and that infection significantly upregulates the expression of cytokines involved in innate immunity (tumor necrosis factor alpha, interleukin-6 [IL-6], IL-18, and, most importantly, type I interferons) along with upregulation of major histocompatibility complex class II, IL-12, and various costimulatory molecules (B7-1, B7-2, CD40, and ICAM-1). Most significantly, TMEV-infected microglia were able to efficiently process and present both endogenous virus epitopes and exogenous myelin epitopes to inflammatory CD4(+) Th1 cells. Thus, TMEV infection of microglia activates these cells to initiate an innate immune response which may lead to the activation of naive and memory virus- and myelin-specific adaptive immune responses within the CNS.",,"['Olson, Julie K.', 'Girvin, Ann M.', 'Miller, Stephen D.']",,,,
,PMC,Molecular Determinants of Species Specificity in the Coronavirus Receptor Aminopeptidase N (CD13):  Influence of N-Linked Glycosylation,http://dx.doi.org/10.1128/JVI.75.20.9741-9752.2001,PMC114546,,,"Aminopeptidase N (APN), a 150-kDa metalloprotease also called CD13, serves as a receptor for serologically related coronaviruses of humans (human coronavirus 229E [HCoV-229E]), pigs, and cats. These virus-receptor interactions can be highly species specific; for example, the human coronavirus can use human APN (hAPN) but not porcine APN (pAPN) as its cellular receptor, and porcine coronaviruses can use pAPN but not hAPN. Substitution of pAPN amino acids 283 to 290 into hAPN for the corresponding amino acids 288 to 295 introduced an N-glycosylation sequon at amino acids 291 to 293 that blocked HCoV-229E receptor activity of hAPN. Substitution of two amino acids that inserted an N-glycosylation site at amino acid 291 also resulted in a mutant hAPN that lacked receptor activity because it failed to bind HCoV-229E. Single amino acid revertants that removed this sequon at amino acids 291 to 293 but had one or five pAPN amino acid substitution(s) in this region all regained HCoV-229E binding and receptor activities. To determine if other N-linked glycosylation differences between hAPN, feline APN (fAPN), and pAPN account for receptor specificity of pig and cat coronaviruses, a mutant hAPN protein that, like fAPN and pAPN, lacked a glycosylation sequon at 818 to 820 was studied. This sequon is within the region that determines receptor activity for porcine and feline coronaviruses. Mutant hAPN lacking the sequon at amino acids 818 to 820 maintained HCoV-229E receptor activity but did not gain receptor activity for porcine or feline coronaviruses. Thus, certain differences in glycosylation between coronavirus receptors from different species are critical determinants in the species specificity of infection.",,"['Wentworth, David E.', 'Holmes, Kathryn V.']",,,,
,PMC,"Localization to the Nucleolus Is a Common Feature of Coronavirus Nucleoproteins, and the Protein May Disrupt  Host Cell Division",http://dx.doi.org/10.1128/JVI.75.19.9345-9356.2001,PMC114503,,,"The subcellular localization of transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) (group I and group II coronaviruses, respectively) nucleoproteins (N proteins) were examined by confocal microscopy. The proteins were shown to localize either to the cytoplasm alone or to the cytoplasm and a structure in the nucleus. This feature was confirmed to be the nucleolus by using specific antibodies to nucleolin, a major component of the nucleolus, and by confocal microscopy to image sections through a cell expressing N protein. These findings are consistent with our previous report for infectious bronchitis virus (group III coronavirus) (J. A. Hiscox et al., J. Virol. 75:506–512, 2001), indicating that nucleolar localization of the N protein is a common feature of the coronavirus family and is possibly of functional significance. Nucleolar localization signals were identified in the domain III region of the N protein from all three coronavirus groups, and this suggested that transport of N protein to the nucleus might be an active process. In addition, our results suggest that the N protein might function to disrupt cell division. Thus, we observed that approximately 30% of cells transfected with the N protein appeared to be undergoing cell division. The most likely explanation for this is that the N protein induced a cell cycle delay or arrest, most likely in the G(2)/M phase. In a fraction of transfected cells expressing coronavirus N proteins, we observed multinucleate cells and dividing cells with nucleoli (which are only present during interphase). These findings are consistent with the possible inhibition of cytokinesis in these cells.",,"['Wurm, Torsten', 'Chen, Hongying', 'Hodgson, Teri', 'Britton, Paul', 'Brooks, Gavin', 'Hiscox, Julian A.']",,,,
,PMC,Protective Immunity and Antibody-Secreting Cell Responses Elicited by Combined Oral Attenuated Wa Human Rotavirus and Intranasal Wa 2/6-VLPs with Mutant Escherichia coli Heat-Labile  Toxin in Gnotobiotic Pigs,http://dx.doi.org/10.1128/JVI.75.19.9229-9238.2001,PMC114490,,,"Two combined rotavirus vaccination regimens were evaluated in a gnotobiotic pig model of rotavirus infection and disease and were compared to previously tested rotavirus vaccination regimens. The first (AttHRV/VLP2×) involved oral inoculation with one dose of attenuated (Att) Wa human rotavirus (HRV), followed by two intranasal (i.n.) doses of a rotavirus-like particle (2/6-VLPs) vaccine derived from Wa (VP6) and bovine RF (VP2) rotavirus strains. The 2/6-VLPs were coadministered with a mutant Escherichia coli heat-labile toxin, LT-R192G (mLT) adjuvant. For the second regimen (VLP2×/AttHRV), two i.n. doses of 2/6-VLPs+mLT were given, followed by one oral dose of attenuated Wa HRV. To compare the protective efficacy and immune responses induced by the combined vaccine regimens with individual rotavirus vaccine regimens, we included in the experiments the following vaccine groups: one oral dose of attenuated Wa HRV (AttHRV1× and Mock2×/AttHRV, respectively), three oral doses of attenuated Wa HRV (AttHRV3×), three i.n. doses of 2/6-VLPs plus mLT (VLP3×), three i.n. doses of purified double-layered inactivated Wa HRV plus mLT (InactHRV3×), mLT alone, and mock-inoculated pigs. The isotype, magnitude, and tissue distribution of antibody-secreting cells (ASCs) in the intestinal and systemic lymphoid tissues were evaluated using an enzyme-linked immunospot assay. The AttHRV/VLP2× regimen stimulated the highest mean numbers of intestinal immunoglobulin A (IgA) ASCs prechallenge among all vaccine groups. This regimen induced partial protection against virus shedding (58%) and diarrhea (44%) upon challenge of pigs with virulent Wa HRV. The reverse VLP2×/AttHRV regimen was less efficacious than the AttHRV/VLP2× regimen in inducing IgA ASC responses and protection against diarrhea (25% protection rate) but was more efficacious than VLP3× or InactHRV3× (no protection). In conclusion, the AttHRV/VLP2× vaccination regimen stimulated the strongest B-cell responses in the intestinal mucosal immune system at challenge and conferred a moderately high protection rate against rotavirus disease, indicating that priming of the mucosal inductive site at the portal of natural infection with a replicating vaccine, followed by boosting with a nonreplicating vaccine at a second mucosal inductive site, may be a highly effective approach to stimulate the mucosal immune system and induce protective immunity against various mucosal pathogens.",,"['Yuan, Lijuan', 'Iosef, Cristiana', 'Azevedo, Marli S. P.', 'Kim, Yunjeong', 'Qian, Yuan', 'Geyer, Annelise', 'Nguyen, Trang Van', 'Chang, Kyeong-Ok', 'Saif, Linda J.']",,,,
,PMC,Cooperation of an RNA Packaging Signal and a Viral Envelope Protein in Coronavirus RNA Packaging,http://dx.doi.org/10.1128/JVI.75.19.9059-9067.2001,PMC114474,,,"Murine coronavirus mouse hepatitis virus (MHV) produces a genome-length mRNA, mRNA 1, and six or seven species of subgenomic mRNAs in infected cells. Among these mRNAs, only mRNA 1 is efficiently packaged into MHV particles. MHV N protein binds to all MHV mRNAs, whereas envelope M protein interacts only with mRNA 1. This M protein-mRNA 1 interaction most probably determines the selective packaging of mRNA 1 into MHV particles. A short cis-acting MHV RNA packaging signal is necessary and sufficient for packaging RNA into MHV particles. The present study tested the possibility that the selective M protein-mRNA 1 interaction is due to the packaging signal in mRNA 1. Regardless of the presence or absence of the packaging signal, N protein bound to MHV defective interfering RNAs and intracellularly expressed non-MHV RNA transcripts to form ribonucleoprotein complexes; M protein, however, interacted selectively with RNAs containing the packaging signal. Moreover, only the RNA that interacted selectively with M protein was efficiently packaged into MHV particles. Thus, it was the packaging signal that mediated the selective interaction between M protein and viral RNA to drive the specific packaging of RNA into virus particles. This is the first example for any RNA virus in which a viral envelope protein and a known viral RNA packaging signal have been shown to determine the specificity and selectivity of RNA packaging into virions.",,"['Narayanan, Krishna', 'Makino, Shinji']",,,,
,PMC,Toxic effects in dairy cattle following the ingestion of a large volume of canola oil.,,PMC1476612,,,"The clinical and laboratory findings of a group of 9 dairy cattle that accidentally ingested large volumes of canola oil are described. Four of the animals died, and 3 were necropsied. No specific cause of death was found, although a number of theories are advanced. This is the first report of such an occurrence.",,"['Clark, C', 'Radostits, O', 'Petrie, L', 'Allen, A']",,,,
,PMC,Presence of Oligoclonal T Cells in Cerebrospinal Fluid of a Child with Multiphasic Disseminated Encephalomyelitis  following Hepatitis A Virus Infection,http://dx.doi.org/10.1128/CDLI.8.5.984-992.2001,PMC96183,,,"We have investigated the clonality of β-chain T-cell receptor (TCR) transcripts from the cerebrospinal fluid (CSF) and peripheral blood from a 7-year old child who developed a multiphasic disseminated encephalomyelitis following an infection with hepatitis A virus. We amplified β-chain TCR transcripts by nonpalindromic adaptor (NPA)-PCR–Vβ-specific PCR. TCR transcripts from only five Vβ families (Vβ13, Vβ3, Vβ17, Vβ8, and Vβ20) were detected in CSF. The amplified products were combined, cloned, and sequenced. Sequence analysis revealed in the CSF substantial proportions of identical β-chain of TCR transcripts, demonstrating oligoclonal populations of T cells. Seventeen of 35 (48%) transcripts were 100% identical, demonstrating a major Vβ13.3 Dβ2.1 Jβ1.3 clonal expansion. Six of 35 (17%) transcripts were also 100% identical, revealing a second Vβ13 clonal expansion (Vβ13.1 Dβ2.1 Jβ1.2). Clonal expansions were also found within the Vβ3 family (transcript Vβ3.1 Dβ2.1 Jβ1.5 accounted for 5 of 35 transcripts [14%]) and within the Vβ20 family (transcript Vβ20.1 Dβ1.1 Jβ2.4 accounted for 3 of 35 transcripts [8%]). These results demonstrate the presence of T-cell oligoclonal expansions in the CSF of this patient following infection with hepatitis A virus. Analysis of the CDR3 motifs revealed that two of the clonally expanded T-cell clones exhibited substantial homology to myelin basic protein-reactive T-cell clones. In contrast, all Vβ TCR families were expressed in peripheral blood lymphocytes. Oligoclonal expansions of T cells were not detected in the peripheral blood of this patient. It remains to be determined whether these clonally expanded T cells are specific for hepatitis A viral antigen(s) or host central nervous system antigen(s) and whether molecular mimicry between hepatitis A viral protein and a host protein is responsible for demyelinating disease in this patient.",,"['Oleszak, Emilia L.', 'Lin, Wan Lu', 'Legido, Agustin', 'Melvin, Joseph', 'Hardison, Huntley', 'Hoffman, Brad E.', 'Katsetos, Christos D.', 'Platsoucas, Chris D.']",,,,
,PMC,Retinopathies Associated with Antiretinal Antibodies,http://dx.doi.org/10.1128/CDLI.8.5.853-858.2001,PMC96159,,,,,"['Hooks, John J.', 'Tso, Mark O. M.', 'Detrick, Barbara']",,,,
,PMC,RNA Splicing at Human Immunodeficiency Virus Type 1  3′ Splice Site A2 Is Regulated by Binding of hnRNP A/B Proteins to an Exonic Splicing Silencer Element,http://dx.doi.org/10.1128/JVI.75.18.8487-8497.2001,PMC115094,,,"The synthesis of human immunodeficiency virus type 1 (HIV-1) mRNAs is a complex process by which more than 30 different mRNA species are produced by alternative splicing of a single primary RNA transcript. HIV-1 splice sites are used with significantly different efficiencies, resulting in different levels of mRNA species in infected cells. Splicing of Tat mRNA, which is present at relatively low levels in infected cells, is repressed by the presence of exonic splicing silencers (ESS) within the two tat coding exons (ESS2 and ESS3). These ESS elements contain the consensus sequence PyUAG. Here we show that the efficiency of splicing at 3′ splice site A2, which is used to generate Vpr mRNA, is also regulated by the presence of an ESS (ESSV), which has sequence homology to ESS2 and ESS3. Mutagenesis of the three PyUAG motifs within ESSV increases splicing at splice site A2, resulting in increased Vpr mRNA levels and reduced skipping of the noncoding exon flanked by A2 and D3. The increase in Vpr mRNA levels and the reduced skipping also occur when splice site D3 is mutated toward the consensus sequence. By in vitro splicing assays, we show that ESSV represses splicing when placed downstream of a heterologous splice site. A1, A1(B), A2, and B1 hnRNPs preferentially bind to ESSV RNA compared to ESSV mutant RNA. Each of these proteins, when added back to HeLa cell nuclear extracts depleted of ESSV-binding factors, is able to restore splicing repression. The results suggest that coordinate repression of HIV-1 RNA splicing is mediated by members of the hnRNP A/B protein family.",,"['Bilodeau, Patricia S.', 'Domsic, Jeffrey K.', 'Mayeda, Akila', 'Krainer, Adrian R.', 'Stoltzfus, C. Martin']",,,,
,PMC,Targeted Disruption of the Ceacam1 (MHVR) Gene Leads to Reduced Susceptibility of Mice to Mouse Hepatitis Virus Infection,http://dx.doi.org/10.1128/JVI.75.17.8173-8186.2001,PMC115062,,,"The CEACAM1 glycoproteins (formerly called biliary glycoproteins; BGP, C-CAM, CD66a, or MHVR) are members of the carcinoembryonic antigen family of cell adhesion molecules. In the mouse, splice variants of CEACAM1 have either two or four immunoglobulin (Ig) domains linked through a transmembrane domain to either a short or a long cytoplasmic tail. CEACAM1 has cell adhesion activity and acts as a signaling molecule, and long-tail isoforms inhibit the growth of colon and prostate tumor cells in rodents. CEACAM1 isoforms serve as receptors for several viral and bacterial pathogens, including the murine coronavirus mouse hepatitis virus (MHV) and Haemophilus influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis in humans. To elucidate the mechanisms responsible for the many biological activities of CEACAM1, we modified the expression of the mouse Ceacam1 gene in vivo. Manipulation of the Ceacam1 gene in mouse embryonic stem cells that contained the Ceacam1a allele yielded a partial knockout. We obtained one line of mice in which the insert in the Ceacam1a gene had sustained a recombination event. This resulted in the markedly reduced expression of the two CEACAM1a isoforms with four Ig domains, whereas the expression of the two isoforms with two Ig domains was doubled relative to that in wild-type BALB/c (+/+) mice. Homozygous (p/p) Ceacam1a-targeted mice (Ceacam1aΔ4D) had no gross tissue abnormalities and were viable and fertile; however, they were more resistant to MHV A59 infection and death than normal (+/+) mice. Following intranasal inoculation with MHV A59, p/p mice developed markedly fewer and smaller lesions in the liver than +/+ or heterozygous (+/p) mice. The titers of virus produced in the livers were 50- to 100-fold lower in p/p mice than in +/p or +/+ mice. p/p mice survived a dose 100-fold higher than the lethal dose of virus for +/+ mice. +/p mice were intermediate between +/+ and p/p mice in susceptibility to liver damage, virus growth in liver, and susceptibility to killing by MHV. Ceacam1a-targeted mice provide a new model to study the effects of modulation of receptor expression on susceptibility to MHV infection in vivo.",,"['Blau, Dianna M.', 'Turbide, Claire', 'Tremblay, Michel', 'Olson, Melanie', 'Létourneau, Stéphanie', 'Michaliszyn, Eva', 'Jothy, Serge', 'Holmes, Kathryn V.', 'Beauchemin, Nicole']",,,,
,PMC,Expression of the Native Cholera Toxin B Subunit Gene and Assembly as Functional Oligomers in Transgenic Tobacco Chloroplasts,http://dx.doi.org/10.1006/jmbi.2001.4921,PMC3473180,,,"The B subunits of enterotoxigenic Escherichia coli (LTB) and cholera toxin of Vibrio cholerae (CTB) are candidate vaccine antigens. Integration of an unmodified CTB-coding sequence into chloroplast genomes (up to 10,000 copies per cell), resulted in the accumulation of up to 4.1% of total soluble tobacco leaf protein as functional oligomers (410-fold higher expression levels than that of the unmodified LTB gene expressed via the nuclear genome). However, expresssion levels reported are an underestimation of actual accumulation of CTB in transgenic chloroplasts, due to aggregation of the oligomeric forms in unboiled samples similar to the aggregation observed for purified bacterial antigen. PCR and Southern blot analyses confirmed stable integration of the CTB gene into the chloroplast genome. Western blot analysis showed that the chloroplast-synthesized CTB assembled into oligomers and were antigenically identical with purified native CTB. Also, binding assays confirmed that chloroplast- synthesized CTB binds to the intestinal membrane GM1-ganglioside receptor, indicating correct folding and disulfide bond formation of CTB pentamers within transgenic chloroplasts. In contrast to stunted nuclear transgenic plants, chloroplast transgenic plants were morphologically indistinguishable from untransformed plants, when CTB was constitutively expressed in chloroplasts. Introduced genes were inherited stably in subsequent generations, as confirmed by PCR and Southern blot analyses. Increased production of an efficient transmucosal carrier molecule and delivery system, like CTB, in transgenic chloroplasts makes plant-based oral vaccines and fusion proteins with CTB needing oral administration commercially feasible. Successful expression of foreign genes in transgenic chromoplasts and availability of marker-free chloroplast transformation techniques augurs well for development of vaccines in edible parts of transgenic plants. Furthermore, since the quaternary structure of many proteins is essential for their function, this investigation demonstrates the potential for other foreign multimeric proteins to be properly expressed and assembled in transgenic chloroplasts.",,"['Daniell, Henry', 'Lee, Seung-Bum', 'Panchal, Tanvi', 'Wiebe, Peter O.']",,,,
,PMC,Steady-state localization of a medial-Golgi glycosyltransferase involves transit through the trans-Golgi network.,,PMC1222029,,,"The steady-state localization of medial-Golgi enzymes is likely to involve retrograde transport pathways; however, the trafficking of these resident enzymes through the Golgi stack is unclear. To investigate if the medial-Golgi enzyme beta-1,2-N-acetylglucosaminyltransferase I (GlcNAc-TI) is transported to the late Golgi, a modified GlcNAc-TI bearing an N-glycan site on the C-terminus was constructed. The modified GlcNAc-TI was demonstrated to be functionally active in vivo, and was localized to the Golgi stack of transfected cells. In stable Chinese-hamster ovary (CHO) cell clones, the N-glycosylated GlcNAc-TI carried sialylated complex N-glycan chains. Pulse-chase studies showed that the majority of GlcNAc-TI was sialylated within 60 min of synthesis. Treatment of transfected CHO cells with Brefeldin A resulted in the glycosylated GlcNAc-TI bearing endo-beta-N-acetylglucosaminidase H resistant chains; however, the sialylation of glycosylated GlcNAc-TI was dramatically reduced. These data imply that, in CHO cells, newly synthesized GlcNAc-TI is transported rapidly through the Golgi stack to the trans-Golgi network, suggesting that GlcNAc-TI continuously recycles from the late Golgi. Furthermore, this data suggests that retrograde transport pathways play an important role in establishing the asymmetric distribution of GlcNAc-TI within the Golgi stack.",,"['Opat, A S', 'Houghton, F', 'Gleeson, P A']",,,,
,PMC,Clinical diagnosis of influenza virus infection: evaluation of diagnostic tools in general practice.,,PMC1314072,,,"BACKGROUND: With the development of new antiviral agents for influenza, the urge for rapid and reliable diagnosis of influenza becomes increasingly important. Respiratory virus infections are difficult to distinguish on clinical grounds. General practitioners (GPs) however, still depend on their clinical judgement. AIM: To evaluate the importance of clinical symptoms in the diagnosis of influenza virus infection. DESIGN OF STUDY: A multicentre questionnaire study. SETTING: Eighty-one patients from 14 general practices. METHOD: Patients with fever and at least one constitutional symptom and one respiratory symptom were included. A questionnaire with the medical history and clinical symptoms was completed and a combined nose-throat swab was taken. Virus culture, rapid culture, and polymerase chain reaction (PCR) amplification were performed on each specimen. Multivariate analysis was used to obtain the best predictive model. RESULTS: By using PCR, an increase was seen in the detection of the viral pathogens compared with the results of culture. In 42 out of 81 patients PCR was positive for influenza. A positive predictive value (PPV) of 75% was observed for the combination of headache at onset, feverishness at onset, cough, and vaccination status during the period of increase influenza activity. Criteria used by the ICHPPC-2 resulted in a PPV of 54%. The PPV for diagnosis made by the GP was 76%. CONCLUSION: Although influenza is difficult to diagnose on clinical grounds, the GPs in this study were able to diagnose influenza as such more accurately on their judgement than by the other criteria.",,"['van Elden, L J', 'van Essen, G A', 'Boucher, C A', 'van Loon, A M', 'Nijhuis, M', 'Schipper, P', 'Verheij, T J', 'Hoepelman, I M']",,,,
,PMC,Sindbis Virus Variant with a Deletion in the 6K Gene Shows Defects in Glycoprotein Processing and Trafficking: Lack of Complementation by a Wild-Type 6K Gene in trans,http://dx.doi.org/10.1128/JVI.75.16.7778-7784.2001,PMC115018,,,"A Sindbis virus (SV) variant with a 6K gene partially deleted has been obtained. This SV Del6K virus is defective in the proteolytic processing of virus glycoprotein precursor, transport of glycoproteins to the plasma membrane, and plaque phenotype. A revertant virus (SV Del6K-revQ21L) containing a point mutation in the deleted 6K gene was isolated and characterized. SV Del6K-revQ21L has corrected the defects of proteolytic processing and transport of virus glycoproteins to the plasma membrane, but it still remains attenuated compared to wild-type (wt) SV, exhibiting defects in virus budding. Neither mutant nor revertant viruses are complemented by the coexpression in trans of a wt SV 6K gene.",,"['Sanz, Miguel Angel', 'Carrasco, Luis']",,,,
,PMC,Downstream Sequences Influence the Choice between a Naturally Occurring Noncanonical and Closely Positioned Upstream  Canonical Heptameric Fusion Motif during Bovine  Coronavirus Subgenomic mRNA Synthesis,http://dx.doi.org/10.1128/JVI.75.16.7362-7374.2001,PMC114971,,,"Mechanisms leading to subgenomic mRNA (sgmRNA) synthesis in coronaviruses are poorly understood but are known to involve a heptameric signaling motif, originally called the intergenic sequence. The intergenic sequence is the presumed crossover region (fusion site) for RNA-dependent RNA polymerase (RdRp) during discontinuous transcription, a process leading to sgmRNAs that are both 5′ and 3′ coterminal. In the bovine coronavirus, the major fusion site for synthesis of mRNA 5 (GGUAGAC) does not conform to the canonical motif (UC[U,C]AAAC) at three positions (underlined), yet it lies just 14 nucleotides downstream from such a sequence (UCCAAAC). The infrequently used canonical sequence, by computer prediction, is buried within the stem of a stable hairpin (−17.2 kcal/mol). Here we document the existence of this stem by enzyme probing and examine its influence and that of neighboring sequences on the unusual choice of fusion sites by analyzing transcripts made in vivo from mutated defective interfering RNA constructs. We learned that (i) mutations that were predicted to unfold the stem-loop in various ways did not switch RdRp crossover to the upstream canonical site, (ii) a totally nonconforming downstream motif resulted in no measurable transcription from either site, (iii) the canonical upstream site does not function ectopically to lend competence to the downstream noncanonical site, and (iv) altering flanking sequences downstream of the downstream noncanonical motif in ways that diminish sequence similarity with the virus genome 5′ end caused a dramatic switch to the upstream canonical site. These results show that sequence elements downstream of the noncanonical site can dramatically influence the choice of fusion sites for synthesis of mRNA 5 and are interpreted as being most consistent with a mechanism of similarity-assisted RdRp strand switching during minus-strand synthesis.",,"['Ozdarendeli, Aykut', 'Ku, Seulah', 'Rochat, Sylvie', 'Williams, Gwyn D.', 'Senanayake, Savithra D.', 'Brian, David A.']",,,,
,PMC,Transcription Factor AP-2α Is Preferentially Cleaved by Caspase 6 and Degraded by Proteasome during Tumor Necrosis Factor  Alpha-Induced Apoptosis in Breast Cancer Cells,http://dx.doi.org/10.1128/MCB.21.15.4856-4867.2001,PMC87191,,,"Several reports have linked activating protein 2α (AP-2α) to apoptosis, leading us to hypothesize that AP-2α is a substrate for caspases. We tested this hypothesis by examining the effects of tumor necrosis factor alpha (TNF-α) on the expression of AP-2 in breast cancer cells. Here, we provide evidence that TNF-α downregulates AP-2α and AP-2γ expression posttranscriptionally during TNF-α-induced apoptosis. Both a general caspase antagonist (zVADfmk) and a caspase 6-preferred antagonist (zVEIDfmk) inhibited TNF-α-induced apoptosis and AP-2α downregulation. In vivo tests showed that AP-2α was cleaved by caspases ahead of the DNA fragmentation phase of apoptosis. Recombinant caspase 6 cleaved AP-2α preferentially, although caspases 1 and 3 also cleaved it, albeit at 50-fold or higher concentrations. Activated caspase 6 was detected in TNF-α-treated cells, thus confirming its involvement in AP-2α cleavage. All three caspases cleaved AP-2α at asp(19) of the sequence asp-arg-his-asp (DRHD(19)). Mutating D(19) to A(19) abrogated AP-2α cleavage by all three caspases. TNF-α-induced cleavage of AP-2α in vivo led to AP-2α degradation and loss of DNA-binding activity, both of which were prevented by pretreatment with zVEIDfmk. AP-2α degradation but not cleavage was inhibited in vivo by PS-431 (a proteasome antagonist), suggesting that AP-2α is degraded subsequent to cleavage by caspase 6 or caspase 6-like enzymes. Cells transfected with green fluorescent protein-tagged mutant AP-2α are resistant to TNF-α-induced apoptosis, further demonstrating the link between caspase-mediated cleavage of AP-2α and apoptosis. This is the first report to demonstrate that degradation of AP-2α is a critical event in TNF-α-induced apoptosis. Since the DRHD sequence in vertebrate AP-2 is widely conserved, its cleavage by caspases may represent an important mechanism for regulating cell survival, proliferation, differentiation, and apoptosis.",,"['Nyormoi, Okot', 'Wang, Zhi', 'Doan, Dao', 'Ruiz, Maribelis', 'McConkey, David', 'Bar-Eli, Menashe']",,,,
,PMC,Ribosomal protein L5 helps anchor peptidyl-tRNA to the P-site in Saccharomyces cerevisiae.,,PMC1307509,,,"Our previous demonstration that mutants of 5S rRNA called mof9 can specifically alter efficiencies of programmed ribosomal frameshifting (PRF) suggested a role for this ubiquitous molecule in the maintenance of translational reading frame, though the repetitive nature of the 5S rDNA gene (>100 copies/cell) inhibited more detailed analyses. However, given the known interactions between 5S rRNA and ribosomal protein L5 (previously called L1 or YL3) encoded by an essential, single-copy gene, we monitored the effects of a series of well-defined rpl5 mutants on PRF and virus propagation. Consistent with the mof9 results, we find that the rpl5 mutants promoted increased frameshifting efficiencies in both the -1 and +1 directions, and conferred defects in the ability of cells to propagate two endogenous viruses. Biochemical analyses demonstrated that mutant ribosomes had decreased affinities for peptidyl-tRNA. Pharmacological studies showed that sparsomycin, a peptidyltransferase inhibitor that specifically increases the binding of peptidyl-tRNA with ribosomes, was antagonistic to the frameshifting defects of the most severe mutant, and the extent of sparsomycin resistance correlated with the severity of the frameshifting defects in all of the mutants. These results provide biochemical and physiological evidence that one function of L5 is to anchor peptidyl-tRNA to the P-site. A model is presented describing how decreased affinity of ribosomes for peptidyl-tRNA can affect both -1 and +1 frameshifting, and for the effects of sparsomycin.",,"['Meskauskas, A', 'Dinman, J D']",,,,
,PMC,The relationship between the occurrence of undifferentiated bovine respiratory disease and titer changes to Haemophilus somnus and Mannheimia haemolytica at 3 Ontario feedlots.,,PMC1189667,,,"The association between exposure to Haemophilus somnus and Mannheimia haemolytica (formerly Pasteurella haemolytica) and the risk of undifferentiated bovine respiratory disease (UBRD) was investigated using serological evidence of exposure coupled with a factorial design vaccine field trial. Measures of previous exposure (titer at arrival) and current exposure (titer increase in the study period) to these agents were used. The vaccine field trial involved systematic allocation of animals into groups that received either a M. haemolytica vaccine, an H. somnus vaccine, a combined M. haemolytica and H. somnus vaccine, and an unvaccinated control group. Serum was collected from the 852 animals enrolled to determine titers to H. somnus, M. haemolytica, bovine coronavirus and bovine viral diarrhea virus. Vaccination with H. somnus in combination with M. haemolytica and with M. haemolytica alone reduced the risk of UBRD. The odds ratio for vaccination with H. somnus alone and UBRD risk suggested some sparing effect, but the 95% confidence limits included unity. There was no association between serological evidence of concurrent exposure to M. haemolytica and UBRD occurrence. There was an association between titer change to H. somnus and UBRD risk. However, the association changed with time of BRD treatment; animals diagnosed and treated for UBRD on or after day 10 showed little evidence of exposure to H. somnus, despite evidence of natural H. somnus exposure in the unvaccinated group. The association between titer change to H. somnus and UBRD occurrence seen in this study may be a consequence of prolonged exposure to antibiotics, rather than a causal association.",,"[""O'Connor, A"", 'Martin, S W', 'Harland, R', 'Shewen, P', 'Menzies, P']",,,,
,PMC,The relationship between the occurrence of undifferentiated bovine respiratory disease and titer changes to bovine coronavirus and bovine viral diarrhea virus in 3 Ontario feedlots.,,PMC1189666,,,"Serological evidence of previous viral exposure (titer at arrival) and current viral exposure (titer increase) during a 28-day study period, was used to determine if bovine coronavirus (BCV) or bovine viral diarrhea virus (BVDV) was associated with the occurrence of undifferentiated bovine respiratory disease (UBRD) in feedlot calves. Neutralizing antibody titers to BCV and BVDV were determined for 852 animals from 3 Ontario feedlots. Calves at 2 of the 3 feedlots (n = 753) received a modified live 4-way viral vaccine containing BVDV. On arrival at the feedlots, 90% of animals were seropositive for BCV, while 39% of animals were seropositive for BVDV. This evidence of previous exposure to both viruses was associated with reduced subsequent UBRD risk. Evidence of exposure to BCV during the study period was common, as 50% of animals showed a 16-fold or greater titer increase; however, treatment for UBRD was not associated with titer change. Although the majority of animals were vaccinated for BVDV at arrival, within a feedlot, animals treated for UBRD had larger titer increases to BVDV than non-treated animals. Based on our findings we infer that BCV was not causally related to UBRD occurrence, however consistent with other literature, BVDV may be causally related to UBRD occurrence.",,"[""O'Connor, A"", 'Martin, S W', 'Nagy, E', 'Menzies, P', 'Harland, R']",,,,
,PMC,Interaction between Mycoplasma hyopneumoniae and  Swine Influenza Virus,http://dx.doi.org/10.1128/JCM.39.7.2525-2530.2001,PMC88180,,,"An experimental respiratory model was used to investigate the interaction between Mycoplasma hyopneumoniae and swine influenza virus (SIV) in the induction of pneumonia in susceptible swine. Previous studies demonstrated that M. hyopneumoniae, which produces a chronic bronchopneumonia in swine, potentiates a viral pneumonia induced by the porcine reproductive and respiratory syndrome virus (PRRSV). In this study, pigs were inoculated with M. hyopneumoniae 21 days prior to inoculation with SIV. Clinical disease as characterized by the severity of cough and fever was evaluated daily. Percentages of lung tissue with visual lesions and microscopic lesions were assessed upon necropsy at 3, 7, 14, and 21 days following SIV inoculation. Clinical observations revealed that pigs infected with both SIV and M. hyopneumoniae coughed significantly more than pigs inoculated with a single agent. Macroscopic pneumonia on necropsy at days 3 and 7 was greatest in both SIV-infected groups, with minimal levels of pneumonia in the M. hyopneumoniae-only-infected pigs. At 14 days post-SIV inoculation, pneumonia was significantly more severe in pigs infected with both pathogens. However, by 21 days postinoculation, the level of pneumonia in the dual-infected pigs was similar to that of the M. hyopneumoniae-only-infected group, and the pneumonia in the pigs inoculated with only SIV was nearly resolved. Microscopically, there was no apparent increase in the severity of pneumonia in pigs infected with both agents compared to that of single-agent-challenged pigs. The results of this study found that while pigs infected with both agents exhibited more severe clinical disease, the relationship between the two pathogens lacked the profound potentiation found with dual infection with M. hyopneumoniae and PRRSV. These findings demonstrate that the relationship between mycoplasmas and viruses varies with the individual agent.",,"['Thacker, Eileen L.', 'Thacker, Brad J.', 'Janke, Bruce H.']",,,,
,PMC,Viral Replicase Gene Products Suffice for Coronavirus Discontinuous Transcription,http://dx.doi.org/10.1128/JVI.75.14.6676-6681.2001,PMC114390,,,"We have used vaccinia virus as a vector to clone a 22.5-kbp cDNA that represents the 5′ and 3′ ends of the human coronavirus 229E (HCoV 229E) genome, the HCoV 229E replicase gene, and a single reporter gene (coding for green fluorescent protein [GFP]) located downstream of a regulatory element for coronavirus mRNA transcription. When RNA transcribed from this cDNA was transfected into BHK-21 cells, a small percentage of cells displayed strong fluorescence. A region of the mRNA encoding GFP was amplified by PCR and shown to have the unique mRNA leader-body junction indicative of coronavirus-mediated transcription. These data show that the coronavirus replicase gene products suffice for discontinuous subgenomic mRNA transcription.",,"['Thiel, Volker', 'Herold, Jens', 'Schelle, Barbara', 'Siddell, Stuart G.']",,,,
,PMC,Induction of Caspase-Dependent Apoptosis in Cultured Cells by the Avian Coronavirus Infectious Bronchitis Virus,http://dx.doi.org/10.1128/JVI.75.14.6402-6409.2001,PMC114363,,,"Avian coronavirus infectious bronchitis virus (IBV) is the causative agent of chicken infectious bronchitis, an acute, highly contagious viral respiratory disease. Replication of IBV in Vero cells causes extensive cytopathic effects (CPE), leading to destruction of the entire monolayer and the death of infected cells. In this study, we investigated the cell death processes during acute IBV infection and the underlying mechanisms. The results show that both necrosis and apoptosis may contribute to the death of infected cells in lytic IBV infection. Caspase-dependent apoptosis, as characterized by chromosomal condensation, DNA fragmentation, caspase-3 activation, and poly(ADP-ribose) polymerase degradation, was detected in IBV-infected Vero cells. Addition of the general caspase inhibitor z-VAD-FMK to the culture media showed inhibition of the hallmarks of apoptosis and increase of the release of virus to the culture media at 16 h postinfection. However, neither the necrotic process nor the productive replication of IBV in Vero cells was severely affected by the inhibition of apoptosis. Screening of 11 IBV-encoded proteins suggested that a 58-kDa mature cleavage product could induce apoptotic changes in cells transiently expressing the protein. This study adds one more example to the growing list of animal viruses that induce apoptosis during their replication cycles.",,"['Liu, C.', 'Xu, H. Y.', 'Liu, D. X.']",,,,
,PMC,Axonal Damage Is T Cell Mediated and Occurs Concomitantly with Demyelination in Mice Infected with a Neurotropic Coronavirus,http://dx.doi.org/10.1128/JVI.75.13.6115-6120.2001,PMC114327,,,"Mice infected with mouse hepatitis virus (MHV) strain JHM develop primary demyelination. Herein we show that axonal damage occurred in areas of demyelination and also in adjacent areas devoid of myelin damage. Immunodeficient MHV-infected RAG1−/− mice (mice defective in recombinase activating gene 1 expression) do not develop demyelination unless they receive splenocytes from a mouse previously immunized against MHV (G. F. Wu, A. Dandekar, L. Pewe, and S. Perlman, J. Immunol. 165:2278–2286, 2000). In the present study, we show that adoptive transfer of T cells was also required for the majority of the axonal injury observed in these animals. Both demyelination and axonal damage were apparent by 7 days posttransfer. Recent data suggest that axonal injury is a major factor in the long-term disability observed in patients with multiple sclerosis. Our data demonstrate that immune system-mediated damage to axons is also a common feature in mice with MHV-induced demyelination. Remarkably, there appeared to be a minimal, if any, interval of time between the appearance of demyelination and that of axonal injury.",,"['Dandekar, Ajai A.', 'Wu, Gregory F.', 'Pewe, Lecia', 'Perlman, Stanley']",,,,
,PMC,The Major Core Protein P4a (A10L Gene) of Vaccinia Virus Is Essential for Correct Assembly of Viral DNA into the Nucleoprotein Complex To Form Immature Viral Particles,http://dx.doi.org/10.1128/JVI.75.13.5778-5795.2001,PMC114294,,,"The vaccinia virus (VV) A10L gene codes for a major core protein, P4a. This polypeptide is synthesized at late times during viral infection and is proteolytically cleaved during virion assembly. To investigate the role of P4a in the virus life cycle and morphogenesis, we have generated an inducer-dependent conditional mutant (VVindA10L) in which expression of the A10L gene is under the control of the Escherichia coli lacI operator/repressor system. Repression of the A10L gene severely impairs virus growth, as observed by both the inability of the virus to form plaques and the 2-log reduction of viral yields. This defect can be partially overcome by addition of the inducer isopropyl-β-d-thiogalactopyranoside (IPTG). Synthesis of viral proteins other than P4a occurred, although early shutoff of host protein synthesis and expression of viral late polypeptides are clearly delayed, both in the absence and in the presence of IPTG, compared with cells infected with the parental virus. Viral DNA replication and concatemer resolution appeared to proceed normally in the absence of the A10L gene product. In cells infected with VVindA10L in the absence of the inducer virion assembly is blocked, as defined by electron microscopy. Numerous spherical immature viral particles that appear devoid of dense viroplasmic material together with highly electron-dense regular structures are abundant in VVindA10L-infected cells. These regularly spaced structures can be specifically labeled with anti-DNA antibodies as well as with a DNase-gold conjugate, indicating that they contain DNA. Some images suggest that these DNA structures enter into spherical immature viral particles. In this regard, although it has not been firmly established, it has been suggested that DNA uptake occurs after formation of spherical immature particles. Overall, our results showed that P4a and/or its cleaved products are essential for the correct assembly of the nucleoprotein complex within immature viral particles.",,"['Heljasvaara, Ritva', 'Rodríguez, Dolores', 'Risco, Cristina', 'Carrascosa, José L.', 'Esteban, Mariano', 'Rodríguez, Juan Ramón']",,,,
,PMC,Genomic Features of Intertypic Recombinant Sabin Poliovirus Strains Excreted by Primary Vaccinees,http://dx.doi.org/10.1128/JVI.75.13.5740-5751.2001,PMC114290,,,"The trivalent oral poliomyelitis vaccine (OPV) contains three different poliovirus serotypes. It use therefore creates particularly favorable conditions for mixed infection of gut cells, and indeed intertypic vaccine-derived recombinants (VdRec) have been frequently found in patients with vaccine-associated paralytic poliomyelitis. Nevertheless, there have not been extensive searches for VdRec in healthy vaccinees following immunization with OPV. To determine the incidence of VdRec and their excretion kinetics in primary vaccinees, and to establish the general genomic features of the corresponding recombinant genomes, we characterized poliovirus isolates excreted by vaccinees following primary immunization with OPV. Isolates were collected from 67 children 2 to 60 days following vaccination. Recombinant strains were identified by multiple restriction fragment length polymorphism assays. The localization of junction sites in recombinant genomes was also determined. VdRec excreted by vaccinees were first detected 2 to 4 days after vaccination. The highest rate of recombinants was on day 14. The frequency of VdRec depends strongly on the serotype of the analyzed isolates (2, 53, and 79% of recombinant strains in the last-excreted type 1, 2, and 3 isolates, respectively). Particular associations of genomic segments were preferred in the recombinant genomes, and recombination junctions were found in the genomic region encoding the nonstructural proteins. Recombination junctions generally clustered in particular subgenomic regions that were dependent on the serotype of the isolate and/or on the associations of genomic segments in recombinants. Thus, VdRec are frequently excreted by vaccinees, and the poliovirus replication machinery requirements or selection factors appear to act in vivo to shape the features of the recombinant genomes.",,"['Cuervo, Nancy Stella', 'Guillot, Sophie', 'Romanenkova, Natalia', 'Combiescu, Mariana', 'Aubert-Combiescu, André', 'Seghier, Mohamed', 'Caro, Valérie', 'Crainic, Radu', 'Delpeyroux, Francis']",,,,
,PMC,The packaging signal of influenza viral RNA molecules.,,PMC1370150,,,"The packaging signal present in influenza viral RNA molecules is shown not to constitute a separate structural element, but to reside within the 5'-bulged promoter structure, as caused by the central unpaired residue A10 in its 5' branch. Upon insertion of two uridine residues in the 3' branch opposite A10, the minus-strand viral RNA (vRNA) promoter is converted into a 3'-bulged structure, whereas the plus-strand cRNA promoter instead adopts the 5'-bulged conformation. In this promoter variant it is exclusively the cRNA that is found packaged in the progeny virions. Upon insertion of only a single uridine nucleotide opposite 5'A10, the two debulged structures of the vRNA and cRNA promoters are rendered identical, and both vRNA and cRNA molecules are packaged indiscriminately, in a 1:1 ratio, but at lower rates. We propose that the binding interactions of viral polymerase with either of the two differently bulged vRNA and cRNA promoter structures result in two different conformations of the enzyme protein. Only the 5' bulged RNA-associated polymerase conformation appears to be recognized for nuclear export, which depends on nuclear matrix protein M1 and nonstructural protein NS2. And the respective wild-type vRNP- or insertion mutant cRNP complex is observed to enter the cytoplasm and hence is included in the viral encapsidation process, which takes place at the plasma membrane.",,"['Tchatalbachev, S', 'Flick, R', 'Hobom, G']",,,,
,PMC,Weimaraner warning.,,PMC1476540,,,,,"McMurray, M",,,,
,PMC,Short-term immunoglobulin A B-cell memory resides in intestinal lymphoid tissues but not in bone marrow of gnotobiotic pigs inoculated with Wa human rotavirus,http://dx.doi.org/10.1046/j.1365-2567.2001.01229.x,PMC1783226,,,"Immunological memory is important for protecting the host from reinfection. To investigate the development and sites of residence of intestinal memory B cells, and their role in protective immunity to reinfection with an enteric virus, we assessed the association between memory B cell and antibody-secreting cell (ASC) responses and protection using a gnotobiotic pig model for human rotavirus (HRV) infection and diarrhoea. The isotypes, quantities and tissue distribution of rotavirus-specific memory B cells and ASC were evaluated prechallenge (28 and 83 postinoculation days [PID]) and postchallenge (7 postchallenge days [PCD]), using enzyme-linked immunospot (ELISPOT) assay, in gnotobiotic pigs inoculated once with virulent or three times with attenuated HRV and challenged at PID 28 with the corresponding virulent HRV. Complete protection against HRV shedding and diarrhoea was associated with significantly higher numbers of immunoglobulin A (IgA) and immunoglobulin G (IgG) memory B cells and ASC in the ileum of virulent HRV-inoculated pigs at challenge. In contrast, pigs inoculated with attenuated HRV had lower numbers of IgA and IgG memory B cells and ASC in intestinal lymphoid tissues, but higher numbers in the spleen. The bone marrow had the lowest mean numbers of IgA and IgG memory B cells and ASC prechallenge in both groups of HRV-inoculated pigs. Therefore, bone marrow was not a site for IgA and IgG rotavirus-specific antibody production or for memory B cells after inoculation with live rotavirus, from 28 PID up to at least 83 PID. The effect of in vitro antigen dose was examined and it was determined to play an important role in the development of ASC from memory B cells for the different tissues examined.",,"['Yuan, Lijuan', 'Geyer, Annelize', 'Saif, Linda J']",,,,
,PMC,"HreP, an In Vivo-Expressed Protease of Yersinia enterocolitica, Is a New Member of the Family of Subtilisin/Kexin-Like Proteases",http://dx.doi.org/10.1128/JB.183.12.3556-3563.2001,PMC95231,,,"The role of proteases in pathogenesis is well established for several microorganisms but has not been described for Yersinia enterocolitica. Previously, we identified a gene, hreP, which showed significant similarity to proteases in a screen for chromosomal genes of Y. enterocolitica that were exclusively expressed during an infection of mice. We cloned this gene by chromosome capture and subsequently determined its nucleotide sequence. Like inv, the gene encoding the invasin protein of Y. enterocolitica, hreP is located in a cluster of flagellum biosynthesis and chemotaxis genes. The genomic organization of this chromosomal region is different in Escherichia coli, Salmonella, and Yersinia pestis than in Y. enterocolitica. Analysis of the distribution of hreP between different Yersinia isolates and the relatively low G+C content of the gene suggests acquisition by horizontal gene transfer. Sequence analysis also revealed that HreP belongs to a family of eukaryotic subtilisin/kexin-like proteases. Together with the calcium-dependent protease PrcA of Anabaena variabilis, HreP forms a new subfamily of bacterial subtilisin/kexin-like proteases which might have originated from a common eukaryotic ancestor. Like other proteases of this family, HreP is expressed with an N-terminal prosequence. Expression of an HreP-His(6) tag fusion protein in E. coli revealed that HreP undergoes autocatalytic processing at a consensus cleavage site of subtilisin/kexin-like proteases, thereby releasing the proprotein.",,"['Heusipp, Gerhard', 'Young, Glenn M.', 'Miller, Virginia L.']",,,,
,PMC,Coinfection of Enteric Helicobacter spp. and Campylobacter spp. in Cats,http://dx.doi.org/10.1128/JCM.39.6.2166-2172.2001,PMC88106,,,"During a 6-year period, 64 of 227 commercially reared cats had microaerobic bacteria isolated from their feces. All the isolates were initially identified as Campylobacter-like organisms based on biochemical and phenotypic characteristics. DNA extractions from 51 of these isolates were subjected to PCR using primers specific for Helicobacter spp. and Campylobacter spp. Of the isolates, 92% (47 of 51 isolates) were positive for Campylobacter spp., 41% (21 of 51 isolates) were positive for Helicobacter spp., 33% (17 of 51 isolates) were positive for both genera, 59% (30 of 51 isolates) were positive only for Campylobacter spp., and 8% (4 of 51) were positive only for Helicobacter spp. Sixteen of the 47 Campylobacter-positive cultures were positive for more than one Campylobacter spp. Based on a species-specific PCR assay, 83% of the isolates were identified as Campylobacter helveticus, 47% of the isolates were identified as Campylobacter upsaliensis, and 6% of the isolates were classified as Campylobacter jejuni. The 1.2-kb PCR products of the 16S rRNA genes of 19 Helicobacter species isolates were subjected to restriction fragment length polymorphism (RFLP) analysis. Of the five different RFLP patterns obtained, two clustered with Helicobacter (“Flexispira”) taxon 8, one clustered with Helicobacter bilis, one clustered with Helicobacter canis, and the remaining pattern was closely related to a novel Helicobacter sp. strain isolated from a woodchuck. The sequence data for the 16S rRNA genes of 10 Helicobacter spp. validated the RFLP-based identification of these isolates. This study demonstrated that biochemical and phenotypic characteristics of microaerobic organisms in cat feces were insufficient to characterize mixed Helicobacter and Campylobacter infections. Molecular structure-based diagnostics using genus- and species-specific PCR, RFLP analysis, and 16S rRNA sequence analysis enabled the identification of multiple microaerobic species in individual animals. The clinical relevance of enteric Helicobacter and Campylobacter coinfection in cats will require further studies.",,"['Shen, Z.', 'Feng, Y.', 'Dewhirst, F. E.', 'Fox, J. G.']",,,,
,PMC,Heterogeneous Nuclear Ribonucleoprotein A1 Binds to the  3′-Untranslated Region and Mediates Potential 5′-3′-End  Cross Talks of Mouse Hepatitis Virus RNA,http://dx.doi.org/10.1128/JVI.75.11.5009-5017.2001,PMC114904,,,"The 3′-untranslated region (3′-UTR) of mouse hepatitis virus (MHV) RNA regulates the replication of and transcription from the viral RNA. Several host cell proteins have previously been shown to interact with this regulatory region. By immunoprecipitation of UV-cross-linked cellular proteins and in vitro binding of the recombinant protein, we have identified the major RNA-binding protein species as heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1). A strong hnRNP A1-binding site was located 90 to 170 nucleotides from the 3′ end of MHV RNA, and a weak binding site was mapped at nucleotides 260 to 350 from the 3′ end. These binding sites are complementary to the sites on the negative-strand RNA that bind another cellular protein, polypyrimidine tract-binding protein (PTB). Mutations that affect PTB binding to the negative strand of the 3′-UTR also inhibited hnRNP A1 binding on the positive strand, indicating a possible relationship between these two proteins. Defective-interfering RNAs containing a mutated hnRNP A1-binding site have reduced RNA transcription and replication activities. Furthermore, hnRNP A1 and PTB, both of which also bind to the complementary strands at the 5′ end of MHV RNA, together mediate the formation of an RNP complex involving the 5′- and 3′-end fragments of MHV RNA in vitro. These studies suggest that hnRNP A1-PTB interactions provide a molecular mechanism for potential 5′-3′ cross talks in MHV RNA, which may be important for RNA replication and transcription.",,"['Huang, Peiyong', 'Lai, Michael M. C.']",,,,
,PMC,Modulation of Transporter Associated with Antigen Processing (TAP)-Mediated Peptide Import into the Endoplasmic Reticulum by Flavivirus Infection,http://dx.doi.org/10.1128/JVI.75.12.5663-5671.2001,PMC114279,,,"In contrast to many other viruses that escape the cellular immune response by downregulating major histocompatibility complex (MHC) class I molecules, flavivirus infection can upregulate their cell surface expression. Previously we have presented evidence that during flavivirus infection, peptide supply to the endoplasmic reticulum is increased (A. Müllbacher and M. Lobigs, Immunity 3:207–214, 1995). Here we show that during the early phase of infection with different flaviviruses, the transport activity of the peptide transporter associated with antigen processing (TAP) is augmented by up to 50%. TAP expression is unaltered during infection, and viral but not host macromolecular synthesis is required for enhanced peptide transport. This study is the first demonstration of transient enhancement of TAP-dependent peptide import into the lumen of the endoplasmic reticulum as a consequence of a viral infection. We suggest that the increased supply of peptides for assembly with MHC class I molecules in flavivirus-infected cells accounts for the upregulation of MHC class I cell surface expression with the biological consequence of viral evasion of natural killer cell recognition.",,"['Momburg, Frank', 'Müllbacher, Arno', 'Lobigs, Mario']",,,,
,PMC,Causes of death in captive Vancouver Island marmots (Marmota vancouverensis) including presumptive pulmonary mycoplasmosis.,,PMC1476496,,,,,"['Raverty, S', 'Black, S']",,,,
,PMC,Evaluation of a Latex Agglutination Kit (Virogen Rotatest) for Detection of Bovine Rotavirus in Fecal Samples,http://dx.doi.org/10.1128/CDLI.8.3.496-498.2001,PMC96089,,,"The performance of the Virogen Rotatest latex agglutination test (LAT) was evaluated for detection of bovine rotavirus antigen. Sixty-three fecal samples from diarrheic calves were collected from November 1999 to May 2000 and screened by LAT, the Rotazyme II enzyme-linked immunosorbent assay (ELISA), and virus isolation (VI) followed by an anti-rotavirus fluorescent-antibody (FA) test to detect the presence of group A rotavirus antigen. Of the 63 samples screened by VI-FA, 33 (58%) tested positive for rotavirus antigen. When the results from the LAT were compared to those from VI-FA, the “gold standard” for detection of bovine rotavirus in fecal samples, the sensitivity and specificity were found to be 87.8 and 73.3%, respectively. Latex agglutination compared with ELISA (the reference method) showed 100% sensitivity and 96.3% specificity, and when ELISA was compared with VI, the sensitivity was 84.8% and the specificity was 73.3%. Latex agglutination is easy to perform in a short time and does not require expensive equipment or skilled personnel, and the reagents have long shelf lives. These factors make the LAT suitable and highly efficient for use in a clinical laboratory as a rapid screening test for bovine rotavirus.",,"['Al-Yousif, Yousif', 'Anderson, Joe', 'Chard-Bergstrom, Cindy', 'Bustamante, Adrian', 'Muenzenberger, Margaret', 'Austin, Kimberly', 'Kapil, Sanjay']",,,,
,PMC,In Utero Infection by Porcine Reproductive and Respiratory Syndrome Virus Is Sufficient To Increase Susceptibility of Piglets to Challenge by Streptococcus suis Type II,http://dx.doi.org/10.1128/JVI.75.10.4889-4895.2001,PMC114243,,,"Porcine reproductive and respiratory syndrome (PRRS) consistently elevates the frequency of disease and mortality in young pigs. Many different secondary bacterial diseases occur in PRRS virus (PRRSV)-infected pigs. However, to date, establishing a reproducible experimental model of PRRSV infection in weaned pigs, with subsequent clinical disease following secondary bacterial challenge, has been difficult. PRRSV is frequently isolated during outbreaks from weak-born piglets affected by secondary bacterial diseases. This study was performed to investigate the potential role of intrauterine PRRSV infection on piglet susceptibility to secondary bacterial infection. PRRSV-free pregnant sows were intranasally infected at 98 days of gestation with PRRSV strain SD 23983. All piglets born to the PRRSV-infected sows were viremic. Piglets were removed from the sows at birth and deprived of colostrum. Piglets from PRRSV-infected and noninfected sows were randomly assigned to Streptococcus suis challenge or control subgroups. At 5 days of age, piglets were challenged intranasally with strain MN 87555 of S. suis type II. Total and differential leukocyte counts were performed on blood samples collected at 3 days of age. The numbers of leukocytes, lymphocytes, and monocytes were significantly reduced in the PRRSV-infected piglets. Lesions were observed in bone marrow, brain, lung, heart, spleen, lymph node, tonsil, and thymus of PRRSV-infected piglets. Thymus/body weight ratios of in utero PRRSV-infected piglets were significantly reduced compared to those of non-PRRSV-infected piglets, and thymic lesions were characterized by severe cortical depletion of thymocytes. Lesions were not observed in piglets born to PRRSV-free sows. Overall, 20 out of 22 piglets in the PRRSV-S. suis dual-infection group died within 1 week after challenge with S. suis (10 of 11 in each of two trials). This contrasts with 1 of 18 piglets in the PRRSV-infection-only group and 5 of 23 piglets in the S. suis-challenge-only group (1 of 12 in trial 1 and 4 of 11 in trial 2). No piglets died in the uninfected control groups. Most of the piglets in the PRRSV-S. suis dual-infection group developed suppurative meningitis. S. suis type II was recovered from their brains and joints. These results indicate that in utero infection by PRRSV makes piglets more susceptible to infection and disease following challenge by S. suis type II. In utero infection by PRRSV may provide a useful model to study the interaction between PRRSV and bacterial coinfections in piglets.",,"['Feng, Wen-hai', 'Laster, S. M.', 'Tompkins, M.', 'Brown, T.', 'Xu, J.-S.', 'Altier, C.', 'Gomez, W.', 'Benfield, D.', 'McCaw, M. B.']",,,,
,PMC,Reovirus Binding to Cell Surface Sialic Acid Potentiates Virus-Induced Apoptosis,http://dx.doi.org/10.1128/JVI.75.9.4029-4039.2001,PMC114148,,,"Reovirus induces apoptosis in cultured cells and in vivo. Genetic studies indicate that the efficiency with which reovirus strains induce apoptosis is determined by the viral S1 gene, which encodes attachment protein ς1. However, the biochemical properties of ς1 that influence apoptosis induction are unknown. To determine whether the capacity of ς1 to bind cell surface sialic acid determines the magnitude of the apoptotic response, we used isogenic reovirus mutants that differ in the capacity to engage sialic acid. We found that T3SA+, a virus capable of binding sialic acid, induces high levels of apoptosis in both HeLa cells and L cells. In contrast, non-sialic-acid-binding strain T3SA− induces little or no apoptosis in these cell types. Differences in the capacity of T3SA− and T3SA+ to induce apoptosis are not due to differences in viral protein synthesis or production of viral progeny. Removal of cell surface sialic acid with neuraminidase abolishes the capacity of T3SA+ to induce apoptosis. Similarly, incubation of T3SA+ with sialyllactose, a trisaccharide comprised of lactose and sialic acid, blocks apoptosis. These findings demonstrate that reovirus binding to cell surface sialic acid is a critical requirement for the efficient induction of apoptosis and suggest that virus receptor utilization plays an important role in regulating cell death.",,"['Connolly, Jodi L.', 'Barton, Erik S.', 'Dermody, Terence S.']",,,,
,PMC,Development of a tRNA-dependent in vitro translation system.,,PMC1370128,,,"A method is described for depleting rabbit reticulocyte lysates and wheat germ extracts of endogenous tRNAs by affinity chromatography using a matrix generated by coupling ethanolamine to epoxy-activated Sepharose 6B. Greater than 90% depletion of tRNA is achieved with the result that translation becomes in effect absolutely dependent on added tRNA. This depletion procedure should prove very useful for studying the influence of tRNA concentration, and the spectrum of the tRNA population, on recoding events such as programmed frameshifting and readthrough of termination codons.",,"['Jackson, R J', 'Napthine, S', 'Brierley, I']",,,,
,PMC,"Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants",,PMC5496653,,,"The use of plants for medicinal purposes dates back thousands of years but genetic engineering of plants to produce desired biopharmaceuticals is much more recent. As the demand for biopharmaceuticals is expected to increase, it would be wise to ensure that they will be available in significantly larger amounts, on a cost-effective basis. Currently, the cost of biopharmaceuticals limits their availability. Plant-derived biopharmaceuticals are cheap to produce and store, easy to scale up for mass production, and safer than those derived from animals. Here, we discuss recent developments in this field and possible environmental concerns.",,"['Daniell, Henry', 'Streatfield, Stephen J.', 'Wycoff, Keith']",,,,
,PMC,Specific Inhibition of Coxsackievirus B3 Translation and Replication by Phosphorothioate Antisense Oligodeoxynucleotides,http://dx.doi.org/10.1128/AAC.45.4.1043-1052.2001,PMC90423,,,"The 5′ and 3′ untranslated regions (UTRs) of coxsackievirus B3 (CVB3) RNA form highly ordered secondary structures that have been confirmed to play important regulatory roles in viral cap-independent internal translation initiation and RNA replication. We previously demonstrated that deletions in different regions of the 5′ UTR significantly reduced viral RNA translation and infectivity. Such observations suggested strongly that viral RNA translation and replication could be blocked if highly specific antisense oligodeoxynucleotides (AS-ODNs) were applied to target crucial sites within the 5′ and 3′ UTRs. In this study, seven phosphorothioate AS-ODNs were synthesized, and the antiviral activity was evaluated by Lipofectin transfection of HeLa cells with AS-ODNs followed by infection of CVB3. Analysis by Western blotting, reverse transcription-PCR, and viral plaque assay demonstrated that viral protein synthesis, genome replication, and infectivity of CVB3 were strongly inhibited by the AS-ODNs complementary to different regions of the 5′ and 3′ UTRs. The most effective sites are located at the proximate terminus of the 5′ UTR (AS-1), the proximate terminus of the 3′ UTR (AS-7), the core sequence of the internal ribosome entry site (AS-2), and the translation initiation codon region (AS-4). These AS-ODNs showed highly sequence-specific and dose-dependent inhibitory effects on both viral protein synthesis and RNA replication. It is noteworthy that the highest inhibitory activities were obtained with AS-1 and AS-7 targeting the termini of the 5′ and 3′ UTRs. The percent inhibition values of AS-1 and AS-7 for CVB3 protein VP1 synthesis and RNA replication were 70.6 and 79.6 for AS-1 and 73.7 and 79.7 for AS-7, respectively. These data suggest that CVB3 infectivity can be inhibited effectively by AS-ODNs.",,"['Wang, Aikun', 'Cheung, Paul K. M.', 'Zhang, Huifang', 'Carthy, Christopher M.', 'Bohunek, Lubos', 'Wilson, Janet E.', 'McManus, Bruce M.', 'Yang, Decheng']",,,,
,PMC,Secretion of Recombinant Proteins via the Chaperone/Usher Pathway in Escherichia coli,http://dx.doi.org/10.1128/AEM.67.4.1805-1814.2001,PMC92801,,,"F1 antigen (Caf1) of Yersinia pestis is assembled via the Caf1M chaperone/Caf1A usher pathway. We investigated the ability of this assembly system to facilitate secretion of full-length heterologous proteins fused to the Caf1 subunit in Escherichia coli. Despite correct processing of a chimeric protein composed of a modified Caf1 signal peptide, mature human interleukin-1β (hIL-1β), and mature Caf1, the processed product (hIL-1β:Caf1) remained insoluble. Coexpression of this chimera with a functional Caf1M chaperone led to the accumulation of soluble hIL-1β:Caf1 in the periplasm. Soluble hIL-1β:Caf1 reacted with monoclonal antibodies directed against structural epitopes of hIL-1β. The results indicate that Caf1M-induced release of hIL-1β:Caf1 from the inner membrane promotes folding of the hIL-1β domain. Similar results were obtained with the fusion of Caf1 to hIL-1β receptor antagonist or to human granulocyte-macrophage colony-stimulating factor. Following coexpression of the hIL-1β:Caf1 precursor with both the Caf1M chaperone and Caf1A outer membrane protein, hIL-1β:Caf1 could be detected on the cell surface of E. coli. These results demonstrate for the first time the potential application of the chaperone/usher secretion pathway in the transport of subunits with large heterogeneous N-terminal fusions. This represents a novel means for the delivery of correctly folded heterologous proteins to the periplasm and cell surface as either polymers or cleavable monomeric domains.",,"['Zavialov, Anton V.', 'Batchikova, Natalia V.', 'Korpela, Timo', 'Petrovskaya, Lada E.', 'Korobko, Vyacheslav G.', 'Kersley, Joanne', 'MacIntyre, Sheila', ""Zav'yalov, Vladimir P.""]",,,,
,PMC,Bovine Rotavirus Nonstructural Protein 4 Produced by Lactococcus lactis Is Antigenic and Immunogenic,http://dx.doi.org/10.1128/AEM.67.4.1423-1428.2001,PMC92750,,,"Rotavirus nonstructural protein 4 (NSP4) can induce diarrhea in mice. To get insight into the biological effects of NSP4, production of large quantities of this protein is necessary. We first tried to produce the protein in Escherichia coli, but the nsp4 gene proved to be unstable. The capacity of the generally regarded as safe organism Lactococcus lactis to produce NSP4 either intra- or extracellularly was then investigated by using the nisin-controlled expression system. Production of recombinant NSP4 (rNSP4) was observed in L. lactis for both locations. In spite of a very low secretion efficiency, the highest level of production was obtained with the fusion between a lactococcal signal peptide and rNSP4. Cultures of the rNSP4-secreting strain were injected into rabbits, and a specific immune response was elicited. The anti-rNSP4 antibodies produced in these rabbits recognized NSP4 in MA104 cells infected by rotavirus. We showed that L. lactis is able to produce antigenic and immunogenic rNSP4 and thus is a good organism for producing viral antigens.",,"['Enouf, Vincent', 'Langella, Philippe', 'Commissaire, Jacqueline', 'Cohen, Jean', 'Corthier, Gérard']",,,,
,PMC,Expression and Self-Assembly in Baculovirus of Porcine Enteric Calicivirus Capsids into Virus-Like Particles and Their Use in an Enzyme-Linked Immunosorbent Assay for Antibody Detection in Swine,http://dx.doi.org/10.1128/JCM.39.4.1487-1493.2001,PMC87958,,,"Porcine enteric calicivirus (PEC) causes diarrhea and intestinal lesions in pigs. PEC strain Cowden grows to low to moderate titers in cell culture but only with the addition of intestinal contents from uninfected gnotobiotic pigs (W. T. Flynn and L. J. Saif, J. Clin. Microbiol. 26:206–212, 1988; A. V. Parwani, W. T. Flynn, K. L. Gadfield, and L. J. Saif, Arch. Virol. 120:115–122, 1991). Cloning and sequence analysis of the PEC Cowden full-length genome revealed that it is most closely related genetically to the human Sapporo-like viruses. In this study, the complete PEC capsid gene was subcloned into the plasmid pBlueBac4.5 and the recombinant baculoviruses were identified by plaque assay and PCR. The PEC capsid protein was expressed in insect (Sf9) cells inoculated with the recombinant baculoviruses, and the recombinant capsid proteins self- assembled into virus-like particles (VLPs) that were released into the cell supernatant and purified by CsCl gradient centrifugation. The PEC VLPs had the same molecular mass (58 kDa) as the native virus capsid and reacted with pig hyperimmune and convalescent-phase sera to PEC Cowden in enzyme-linked immunosorbent assay (ELISA) and Western blotting. The PEC capsid VLPs were morphologically and antigenically similar to the native virus by immune electron microscopy. High titers (1:102,400 to 204,800) of PEC-specific antibodies were induced in guinea pigs inoculated with PEC VLPs, suggesting that the VLPs could be useful for future candidate PEC vaccines. A fixed-cell ELISA and VLP ELISA were developed to detect PEC serum antibodies in pigs. For the fixed-cell ELISA, Sf9 cells were infected with recombinant baculoviruses expressing PEC capsids, followed by cell fixation with formalin. For the VLP ELISA, the VLPs were used for the coating antigen. Our data indicate that both tests were rapid, specific, and reproducible and might be used for large-scale serological investigations of PEC antibodies in swine.",,"['Guo, Mingzhang', 'Qian, Yuan', 'Chang, Kyeong-Ok', 'Saif, Linda J.']",,,,
,PMC,Biogenesis of the Semliki Forest Virus RNA Replication Complex,http://dx.doi.org/10.1128/JVI.75.8.3873-3884.2001,PMC114878,,,"The nonstructural (ns) proteins nsP1 to -4, the components of Semliki Forest virus (SFV) RNA polymerase, were localized in infected cells by confocal microscopy using double labeling with specific antisera against the individual ns proteins. All ns proteins were associated with large cytoplasmic vacuoles (CPV), the inner surfaces of which were covered by small invaginations, or spherules, typical of alphavirus infection. All ns proteins were localized by immuno-electron microscopy (EM) to the limiting membranes of CPV and to the spherules, together with newly labeled viral RNA. Along with earlier observations by EM-autoradiography (P. M. Grimley, I. K. Berezesky, and R. M. Friedman, J. Virol. 2:326–338, 1968), these results suggest that individual spherules represent template-associated RNA polymerase complexes. Immunoprecipitation of radiolabeled ns proteins showed that each antiserum precipitated the other three ns proteins, implying that they functioned as a complex. Double labeling with organelle-specific and anti-ns-protein antisera showed that CPV were derivatives of late endosomes and lysosomes. Indeed, CPV frequently contained endocytosed bovine serum albumin-coated gold particles, introduced into the medium at different times after infection. With time, increasing numbers of spherules were also observed on the cell surfaces; they were occasionally released into the medium, probably by secretory lysosomes. We suggest that the spherules arise by primary assembly of the RNA replication complexes at the plasma membrane, guided there by nsP1, which has affinity to lipids specific for the cytoplasmic leaflet of the plasma membrane. Endosomal recycling and fusion of CPV with the plasma membrane can circulate spherules between the plasma membrane and the endosomal-lysosomal compartment.",,"['Kujala, Pekka', 'Ikäheimonen, Anne', 'Ehsani, Neda', 'Vihinen, Helena', 'Auvinen, Petri', 'Kääriäinen, Leevi']",,,,
,PMC,Mitochondrial Aconitase Binds to the 3′ Untranslated Region of the Mouse Hepatitis Virus Genome,http://dx.doi.org/10.1128/JVI.75.7.3352-3362.2001,PMC114128,,,"Mouse hepatitis virus (MHV), a member of the Coronaviridae, contains a polyadenylated positive-sense single-stranded genomic RNA which is 31 kb long. MHV replication and transcription take place via the synthesis of negative-strand RNA intermediates from a positive-strand genomic template. A cis-acting element previously identified in the 3′ untranslated region binds to trans-acting host factors from mouse fibroblasts and forms at least three RNA-protein complexes. The largest RNA-protein complex formed by the cis-acting element and the lysate from uninfected mouse fibroblasts has a molecular weight of about 200 kDa. The complex observed in gel shift assays has been resolved by second-dimension sodium dodecyl sulfate-polyacrylamide gel electrophoresis into four proteins of approximately 90, 70, 58, and 40 kDa after RNase treatment. Specific RNA affinity chromatography also has revealed the presence of a 90-kDa protein associated with RNA containing the cis-acting element bound to magnetic beads. The 90-kDa protein has been purified from uninfected mouse fibroblast crude lysates. Protein microsequencing identified the 90-kDa protein as mitochondrial aconitase. Antibody raised against purified mitochondrial aconitase recognizes the RNA-protein complex and the 90-kDa protein, which can be released from the complex by RNase digestion. Furthermore, UV cross-linking studies indicate that highly purified mitochondrial aconitase binds specifically to the MHV 3′ protein-binding element. Increasing the intracellular level of mitochondrial aconitase by iron supplementation resulted in increased RNA-binding activity in cell extracts and increased virus production as well as viral protein synthesis at early hours of infection. These results are particularly interesting in terms of identification of an RNA target for mitochondrial aconitase, which has a cytoplasmic homolog, cytoplasmic aconitase, also known as iron regulatory protein 1, a well-recognized RNA-binding protein. The binding properties of mitochondrial aconitase and the functional relevance of RNA binding appear to parallel those of cytoplasmic aconitase.",,"['Nanda, Santosh K.', 'Leibowitz, Julian L.']",,,,
,PMC,Epitope Mapping Porcine Reproductive and Respiratory Syndrome Virus by Phage Display: the nsp2 Fragment of the Replicase Polyprotein Contains a Cluster of B-Cell Epitopes,http://dx.doi.org/10.1128/JVI.75.7.3277-3290.2001,PMC114121,,,"We screened phage display libraries of porcine reproductive and respiratory syndrome virus (PRRSV) protein fragments with sera from experimentally infected pigs to identify linear B-cell epitopes that are commonly recognized during infection in vivo. We identified 10 linear epitope sites (ES) 11 to 53 amino acids in length. In the replicase polyprotein, a total of eight ES were identified, six of which localized to the Nsp2 replicase polyprotein processing end product. In the structural proteins, a total of two ES were identified, in the ORF3 and ORF4 minor envelope glycoproteins. The ORF4 ES was previously identified by monoclonal antibody mapping (J. J. M. Meulenberg, A. P. van Nieuwstadt, A. van Essen-Zandenbergen, and J. P. M. Langeveld, J. Virol. 71:6061–6067, 1997), but its immunogenicity had not been examined in pigs. We found that six experimentally PRRSV-infected pigs consistently had very high antibody titers against the ORF4 ES. In some animals, sera diluted 1:62,500 still gave weak positive enzyme immunoassay reactivity against the ORF4 ES. This hitherto unrecognized immunodominance likely caused phages displaying the ORF4 ES to outcompete phages displaying other ES during library screening with porcine sera and accounted for our failure to identify more than two ES in the structural genes of PRRSV. Genetic analysis showed that variable ES were also the most immunogenic in vivo. Serological analysis indicated differences in the immunoglobulin A responses between short-term and longer-term viremic pigs towards some ES. The implications of these findings for PRRSV diagnostics and immunopathogenesis are discussed.",,"['Oleksiewicz, M. B.', 'Bøtner, A.', 'Toft, P.', 'Normann, P.', 'Storgaard, T.']",,,,
,PMC,Herpes Simplex Virus-Induced Keratitis: Evaluation of the Role of Molecular Mimicry in Lesion Pathogenesis,http://dx.doi.org/10.1128/JVI.75.7.3077-3088.2001,PMC114101,,,"Viruses are suspected but usually unproven triggering factors in autoimmunity. One favored mechanism to explain the role of viruses in the genesis of autoimmunity is molecular mimicry. An immunoinflammatory blinding lesion called herpetic stromal keratitis (HSK) that follows ocular infection with herpes simplex virus (HSV) is suggested to result from a CD4(+) T-cell response to a UL6 peptide of HSV that cross-reacts with a corneal autopeptide shared with the immunoglobulin G2a(b) (IgG2a(b)) isotype. The present report reevaluates the molecular mimicry hypothesis to explain HSK pathogenesis. Our results failed to reveal cross-reactivity between the UL6 and IgG2a(b) peptides or between peptide reactive T cells and HSV antigens. More importantly, animals infected with HSV failed to develop responses that reacted with either peptide, and infection with a recombinant vaccinia UL6 vector failed to cause HSK, in spite of generating UL6 reactivity. Other lines of evidence also failed to support the molecular mimicry hypothesis, such as the failure to affect HSK severity upon tolerization of susceptible BALB/c and B-cell-deficient mice with IgG2a(b) or UL6 peptides. An additional study system revealed that HSK could be induced in mouse strains, such as the OT2 × RAG1(−/−) mice (T cell receptor transgenic recognizing OVA(323–339)) that were unable to produce CD4(+) T-cell responses to any detectable HSV antigens. Our results cast doubt on the molecular mimicry hypothesis as an explanation for the pathogenesis of HSK and indicate that if autoimmunity is involved its likely proceeds via a bystander activation mechanism.",,"['Deshpande, Shilpa P.', 'Lee, Sujin', 'Zheng, Mei', 'Song, Byeongwoon', 'Knipe, David', 'Kapp, Judith A.', 'Rouse, Barry T.']",,,,
,PMC,Antigen-specific IgG antibodies in stage IV long-time survival breast cancer patients.,,PMC1950034,,,"BACKGROUND: Profiling the immune responses in patients with cancer is expected to facilitate the design of diagnostic tests and therapeutic vaccines. Such studies usually require the parental antigens. We attempted to profile the immune responses in patients with breast cancer using a peptide phage display selection strategy, which identifies antibody specificities whether or not the antigens are known. MATERIALS AND METHODS: A panel of random peptide phage libraries was panned on serum IgG antibodies from breast cancer patients with stage IV, seeking for disease specific IgG epitopes. ELISA, immunoscreening, and Western blotting techniques were the main approaches used. RESULTS: Phage-displayed peptides were specifically enriched for binding to IgG antibodies from patients with breast cancer. Several peptides have been identified, in particular the SQRIPARIHHFPTSI peptide, which was recognized by IgG antibodies from breast cancer patients, but not from normals (p < 0.0004). In patients who responded to the selected peptides, in particular the SQRIPARIHHFPTSI peptide, antibodies against a 66 kDa cellular protein were found. Interestingly, three out of six patients with the strongest immunoreactivity are still alive, with a mean survival time from first recurrence until now of 2553 days. In contrast, all the nonresponders (n = 10) are deceased. The mean survival time of these patients was 784 days, whereas the mean survival time of the three deceased responders was 1050 days (p < 0.02). CONCLUSIONS: The data provide the first example in which panning of peptide phage display libraries on patient IgG antibodies results in the isolation of breast cancer specific IgG epitopes, some of which correlate with patient survival time. Thus, the identified B-cell epitopes should be of great interest in vaccine development.",,"['Hansen, M. H.', 'Ostenstad, B.', 'Sioud, M.']",,,,
,PMC,Infectivity-Neutralizing and Hemagglutinin-Inhibiting Antibody Responses to Respiratory Coronavirus Infections of Cattle in Pathogenesis of Shipping Fever Pneumonia,http://dx.doi.org/10.1128/CDLI.8.2.357-362.2001,PMC96063,,,"Respiratory bovine coronaviruses (RBCV) emerged as an infectious agent most frequently isolated from respiratory tract samples of cattle with acute respiratory tract diseases. Infectivity-neutralizing (IN) and hemagglutinin-inhibiting (HAI) antibodies induced by RBCV infections were monitored in sequential serum samples collected from cattle during a naturally evolving and experimentally monitored epizootic of shipping fever pneumonia (SFP). Cattle nasally shedding RBCV at the beginning of the epizootic started with low levels of serum IN and HAI antibodies. An increase in serum IN antibody after day 7 led to reduction of virus shedding in nasal secretions by the majority of the cattle between days 7 and 14. A substantial rise in the serum HAI antibody was observed during the initial phase among the sick but not the clinically normal cattle which were infected with RBCV. The RBCV isolation-positive cattle that developed fatal SFP had minimal serum IN and HAI antibodies during the course of disease development. Cattle that remained negative in RBCV isolation tests entered this epizootic with high levels of serum IN and HAI antibodies, which dramatically increased during the next two weeks. Protection against SFP was apparently associated with significantly higher levels of serum IN antibodies at the beginning of the epizootic. The RBCV-neutralizing activity is associated with serum immunoglobulin G (IgG), particularly the IgG2 subclass, while RBCV-specific HAI antibody is related to both serum IgG and IgM fractions.",,"['Lin, Xiaoqing', ""O'Reilly, Kathy L."", 'Burrell, Mamie L.', 'Storz, Johannes']",,,,
,PMC,A Single Amino Acid Change within Antigenic Domain II of the Spike Protein of Bovine Coronavirus Confers  Resistance to Virus Neutralization,http://dx.doi.org/10.1128/CDLI.8.2.297-302.2001,PMC96053,,,"The spike glycoprotein is a major neutralizing antigen of bovine coronavirus (BCV). Conformational neutralizing epitopes of group A and group B monoclonal antibodies (MAbs) have previously been mapped to two domains at amino acids 351 to 403 (domain I) and amino acids 517 to 621 (domain II). To further map antigenic sites, neutralization escape mutants of BCV were selected with a group A MAb which has both in vitro and in vivo virus-neutralizing ability. The escape mutants were demonstrated to be neutralization resistant to the selecting group A MAb and remained sensitive to neutralization by a group B MAb. In radioimmunoprecipitation assays, the spike proteins of neutralization escape mutants were shown to have lost their reactivities with the selecting group A MAb. Sequence analysis of the spike protein genes of the escape mutants identified a single nucleotide substitution of C to T at position 1583, resulting in the change of alanine to valine at amino acid position 528 (A528V). The mutation occurs in domain II and in a location which corresponds to the hypervariable region of the spike protein of the coronavirus mouse hepatitis virus. Experimental introduction of the A528V mutation into the wild-type spike protein resulted in the loss of MAb binding of the mutant protein, confirming that the single point mutation was responsible for the escape of BCV from immunological selective pressure.",,"['Yoo, Dongwan', 'Deregt, Dirk']",,,,
,PMC,Identification of Canine Coronavirus Strains from Feces by S Gene Nested PCR and Molecular Characterization of  a New Australian Isolate,http://dx.doi.org/10.1128/JCM.39.3.1036-1041.2001,PMC87870,,,"A nested PCR (nPCR) assay for the detection of canine coronavirus (CCV) in fecal samples is described. The target sequence for the assay was a 514-bp fragment within the spike (S) glycoprotein gene. The sensitivity of the assay is extremely high, detecting as little as 25 50% tissue culture infective doses per g of unprocessed feces. A clinical trial using dogs challenged orally with CCV SA4 and CCV NVSL was used to compare viral isolation and the nPCR assay as detection techniques over a 2-week period of infection. Virus isolation detected CCV shedding from day 4 to 9 postchallenge, while the nPCR assay detected CCV shedding from day 4 to 13 postchallenge. Cloning and sequencing of the nPCR assay product enabled investigation of the evolutionary relationships between strains within the S gene. The simple and rapid procedure described here makes this assay an ideal alternative technique to electron microscopy and viral isolation in cell culture for detection of CCV shedding in feces. The described assay also provides a method of identifying new strains of CCV without the complicated and time-consuming practice of raising antibodies to individual strains. This is illustrated by the identification, for the first time, of an Australian isolate of CCV (UWSMN-1).",,"['Naylor, Matthew J.', 'Harrison, Gavan A.', 'Monckton, Robert P.', 'McOrist, Steven', 'Lehrbach, Philip R.', 'Deane, Elizabeth M.']",,,,
,PMC,"High-Magnitude, Virus-Specific CD4 T-Cell Response in the Central Nervous System of Coronavirus-Infected Mice",http://dx.doi.org/10.1128/JVI.75.6.3043-3047.2001,PMC115934,,,"The neurotropic JHM strain of mouse hepatitis virus (MHV) causes acute encephalitis and chronic demyelinating encephalomyelitis in rodents. Previous results indicated that CD8 T cells infiltrating the central nervous system (CNS) were largely antigen specific in both diseases. Herein we show that by 7 days postinoculation, nearly 30% of the CD4 T cells in the acutely infected CNS were MHV specific by using intracellular gamma interferon (IFN-γ) staining assays. In mice with chronic demyelination, 10 to 15% of the CD4 T cells secreted IFN-γ in response to MHV-specific peptides. Thus, these results show that infection of the CNS is characterized by a large influx of CD4 T cells specific for MHV and that these cells remain functional, as measured by cytokine secretion, in mice with chronic demyelination.",,"['Haring, Jodie S.', 'Pewe, Lecia L.', 'Perlman, Stanley']",,,,
,PMC,Sequences at the 3′ Untranslated Region of Bamboo Mosaic Potexvirus RNA Interact with the Viral RNA-Dependent RNA Polymerase,http://dx.doi.org/10.1128/JVI.75.6.2818-2824.2001,PMC115907,,,"The 3′ untranslated region (UTR) of bamboo mosaic potexvirus (BaMV) genomic RNA was found to fold into a series of stem-loop structures including a pseudoknot structure. These structures were demonstrated to be important for viral RNA replication and were believed to be recognized by the replicase (C.-P. Cheng and C.-H. Tsai, J. Mol. Biol. 288:555–565, 1999). Electrophoretic mobility shift and competition assays have now been used to demonstrate that the Escherichia coli-expressed RNA-dependent RNA polymerase domain (Δ893) derived from BaMV open reading frame 1 could specifically bind to the 3′ UTR of BaMV RNA. No competition was observed when bovine liver tRNAs or poly(I)(C) double-stranded homopolymers were used as competitors, and the cucumber mosaic virus 3′ UTR was a less efficient competitor. Competition analysis with different regions of the BaMV 3′ UTR showed that Δ893 binds to at least two independent RNA binding sites, stem-loop D and the poly(A) tail. Footprinting analysis revealed that Δ893 could protect the sequences at loop D containing the potexviral conserved hexamer motif and part of the stem of domain D from chemical cleavage.",,"['Huang, Cheng-Yen', 'Huang, Yih-Leh', 'Meng, Menghsiao', 'Hsu, Yau-Heiu', 'Tsai, Ching-Hsiu']",,,,
,PMC,Virus-Neutralizing Monoclonal Antibody Expressed in Milk  of Transgenic Mice Provides Full Protection against Virus-Induced Encephalitis,http://dx.doi.org/10.1128/JVI.75.6.2803-2809.2001,PMC115905,,,"Neutralizing antibodies represent a major host defense mechanism against viral infections. In mammals, passive immunity is provided by neutralizing antibodies passed to the offspring via the placenta or the milk as immunoglobulin G and secreted immunoglobulin A. With the long-term goal of producing virus-resistant livestock, we have generated mice carrying transgenes that encode the light and heavy chains of an antibody that is able to neutralize the neurotropic JHM strain of murine hepatitis virus (MHV-JHM). MHV-JHM causes acute encephalitis and acute and chronic demyelination in susceptible strains of mice and rats. Transgene expression was targeted to the lactating mammary gland by using the ovine β-lactoglobulin promoter. Milk from these transgenic mice contained up to 0.7 mg of recombinant antibody/ml. In vitro analysis of milk derived from different transgenic lines revealed a linear correlation between antibody expression and virus-neutralizing activity, indicating that the recombinant antibody is the major determinant of MHV-JHM neutralization in murine milk. Offspring of transgenic and control mice were challenged with a lethal dose of MHV-JHM. Litters suckling nontransgenic dams succumbed to fatal encephalitis, whereas litters suckling transgenic dams were fully protected against challenge, irrespective of whether they were transgenic. This demonstrates that a single neutralizing antibody expressed in the milk of transgenic mice is sufficient to completely protect suckling offspring against MHV-JHM-induced encephalitis.",,"['Kolb, Andreas F.', 'Pewe, Lecia', 'Webster, John', 'Perlman, Stanley', 'Whitelaw, C. Bruce A.', 'Siddell, Stuart G.']",,,,
,PMC,Variations in Disparate Regions of the Murine Coronavirus Spike Protein Impact the Initiation of Membrane Fusion,http://dx.doi.org/10.1128/JVI.75.6.2792-2802.2001,PMC115904,,,"The prototype JHM strain of murine hepatitis virus (MHV) is an enveloped, RNA-containing coronavirus that has been selected in vivo for extreme neurovirulence. This virus encodes spike (S) glycoproteins that are extraordinarily effective mediators of intercellular membrane fusion, unique in their ability to initiate fusion even without prior interaction with the primary MHV receptor, a murine carcinoembryonic antigen-related cell adhesion molecule (CEACAM). In considering the possible role of this hyperactive membrane fusion activity in neurovirulence, we discovered that the growth of JHM in tissue culture selected for variants that had lost murine CEACAM-independent fusion activity. Among the collection of variants, mutations were identified in regions encoding both the receptor-binding (S1) and fusion-inducing (S2) subunits of the spike protein. Each mutation was separately introduced into cDNA encoding the prototype JHM spike, and the set of cDNAs was expressed using vaccinia virus vectors. The variant spikes were similar to that of JHM in their assembly into oligomers, their proteolysis into S1 and S2 cleavage products, their transport to cell surfaces, and their affinity for a soluble form of murine CEACAM. However, these tissue culture-adapted spikes were significantly stabilized as S1-S2 heteromers, and their entirely CEACAM-dependent fusion activity was delayed or reduced relative to prototype JHM spikes. The mutations that we have identified therefore point to regions of the S protein that specifically regulate the membrane fusion reaction. We suggest that cultured cells, unlike certain in vivo environments, select for S proteins with delayed, CEACAM-dependent fusion activities that may increase the likelihood of virus internalization prior to the irreversible uncoating process.",,"['Krueger, Dawn K.', 'Kelly, Sean M.', 'Lewicki, Daniel N.', 'Ruffolo, Rosanna', 'Gallagher, Thomas M.']",,,,
,PMC,Murine Coronavirus Spike Protein Determines the Ability of  the Virus To Replicate in the Liver and Cause Hepatitis,http://dx.doi.org/10.1128/JVI.75.5.2452-2457.2001,PMC114828,,,"Recombinant mouse hepatitis viruses (MHV) differing only in the spike gene, containing A59, MHV-4, and MHV-2 spike genes in the background of the A59 genome, were compared for their ability to replicate in the liver and induce hepatitis in weanling C57BL/6 mice infected with 500 PFU of each virus by intrahepatic injection. Penn98-1, expressing the MHV-2 spike gene, replicated to high titer in the liver, similar to MHV-2, and induced severe hepatitis with extensive hepatocellular necrosis. S(A59)R13, expressing the A59 spike gene, replicated to a somewhat lower titer and induced moderate to severe hepatitis with zonal necrosis, similar to MHV-A59. S(4)R21, expressing the MHV-4 spike gene, replicated to a minimal extent and induced few if any pathological changes, similar to MHV-4. Thus, the extent of replication and the degree of hepatitis in the liver induced by these recombinant viruses were determined largely by the spike protein.",,"['Navas, Sonia', 'Seo, Su-Hun', 'Chua, Ming Ming', 'Sarma, Jayasri Das', 'Lavi, Ehud', 'Hingley, Susan T.', 'Weiss, Susan R.']",,,,
,PMC,Generation and Characterization of a Mammalian Cell Line Continuously Expressing Japanese Encephalitis Virus Subviral Particles,http://dx.doi.org/10.1128/JVI.75.5.2204-2212.2001,PMC114804,,,"We have generated a cell line (F cells) producing a secreted form of Japanese encephalitis virus (JEV) subviral particle (extracellular particles [EPs]) that contains the JEV envelope glycoprotein (E) and a precursor (prM) of the virion membrane protein (M). The F cells were engineered to synthesize these JEV products from a cDNA encoding a mutated (furin proteinase resistant) form of prM, since stable cell lines expressing E and the authentic form of prM could not be obtained, due (in part) to the cell-fusing ability of EPs containing E and M. Our biochemical alteration of the prM protein was critical for the successful production of EP-producing cell lines. EPs produced by F cells share the biochemical properties of empty viral particles produced by JEV-infected cells, except that the F-cell EPs lack hemagglutinating activity and M. F-cell EPs were recognized by a panel of monoclonal antibodies to E, and EPs were shown to be useful as vaccine candidates in mice and as diagnostic reagents in evaluating human immune responses to JE vaccination. The amounts of E antigen released into the culture fluid of F cells were similar to those found in virion fractions of JEV-infected cell culture fluids or JEV-infected weanling mouse brains (the current source of antigen used to produce human vaccines for JE). Thus, the F-cell line would appear to be a useful source of antigen for JE vaccines and diagnostics.",,"['Konishi, Eiji', 'Fujii, Atsuko', 'Mason, Peter W.']",,,,
,PMC,Yellow Fever Virus Encephalitis: Properties of the Brain-Associated T-Cell Response during Virus Clearance in  Normal and Gamma Interferon-Deficient Mice and Requirement for CD4(+) Lymphocytes,http://dx.doi.org/10.1128/JVI.75.5.2107-2118.2001,PMC114795,,,"Viral encephalitis caused by neuroadapted yellow fever 17D virus (PYF) was studied in parental and gamma interferon (IFN-γ)-deficient (IFN-γ knockout [GKO]) C57BL/6 mice. The T-cell responses which enter the brain during acute fatal encephalitis of nonimmunized mice, as well as nonfatal encephalitis of immunized mice, were characterized for relative proportions of CD4(+) and CD8(+) cells, their proliferative responses, and antigen-specific expression of cytokines during stimulation in vitro. Unimmunized mice accumulated only low levels of T cells within the brain during fatal disease, whereas the brains of immunized mice contained higher levels of both T-cell subsets in response to challenge, with CD8(+) cells increased relative to the CD4(+) subset. The presence of T cells correlated with the time at which virus was cleared from the central nervous system in both parental and GKO mice. Lymphocytes isolated from the brains of challenged immunized mice failed to proliferate in vitro in response to T-cell mitogens or viral antigens; however, IFN-γ, interleukin 4 (IL-4), and, to a lesser extent, IL-2 were detectable after stimulation. The levels of IFN-γ, but not IL-2 or IL-4, were augmented in response to viral antigen, and this specificity was detectable in the CD4(+) compartment. When tested for the ability to survive both immunization and challenge with PYF virus, GKO and CD8 knockout mice did not differ from parental mice (80 to 85% survival), although GKO mice exhibited a defect in virus clearance. In contrast, CD4 knockout and Igh-6 mice were unable to resist challenge. The data implicate antibody in conjunction with CD4(+) lymphocytes bearing a Th1 phenotype as the critical factors involved in virus clearance in this model.",,"['Liu, Ting', 'Chambers, Thomas J.']",,,,
,PMC,Mutation of Host Δ9 Fatty Acid Desaturase Inhibits Brome Mosaic Virus RNA Replication between Template  Recognition and RNA Synthesis,http://dx.doi.org/10.1128/JVI.75.5.2097-2106.2001,PMC114794,,,"All positive-strand RNA viruses assemble their RNA replication complexes on intracellular membranes. Brome mosaic virus (BMV) replicates its RNA in endoplasmic reticulum (ER)-associated complexes in plant cells and the yeast Saccharomyces cerevisiae. BMV encodes RNA replication factors 1a, with domains implicated in RNA capping and helicase functions, and 2a, with a central polymerase-like domain. Factor 1a interacts independently with the ER membrane, viral RNA templates, and factor 2a to form RNA replication complexes on the perinuclear ER. We show that BMV RNA replication is severely inhibited by a mutation in OLE1, an essential yeast chromosomal gene encoding Δ9 fatty acid desaturase, an integral ER membrane protein and the first enzyme in unsaturated fatty acid synthesis. OLE1 deletion and medium supplementation show that BMV RNA replication requires unsaturated fatty acids, not the Ole1 protein, and that viral RNA replication is much more sensitive than yeast growth to reduced unsaturated fatty acid levels. In ole1 mutant yeast, 1a still becomes membrane associated, recruits 2a to the membrane, and recognizes and stabilizes viral RNA templates normally. However, RNA replication is blocked prior to initiation of negative-strand RNA synthesis. The results show that viral RNA synthesis is highly sensitive to lipid composition and suggest that proper membrane fluidity or plasticity is essential for an early step in RNA replication. The strong unsaturated fatty acid dependence also demonstrates that modulating fatty acid balance can be an effective antiviral strategy.",,"['Lee, Wai-Ming', 'Ishikawa, Masayuki', 'Ahlquist, Paul']",,,,
,PMC,Comparative mutational analysis  of cis-acting RNA signals for translational frameshifting  in HIV-1 and HTLV-2,,PMC29715,,,"Human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia virus type II (HTLV-2) use a similar mechanism for –1 translational frameshifting to overcome the termination codon in viral RNA at the end of the gag gene. Previous studies have identified two important RNA signals for frameshifting, the slippery sequence and a downstream stem–loop structure. However, there have been somewhat conflicting reports concerning the individual contributions of these sequences. In this study we have performed a comprehensive mutational analysis of the cis-acting RNA sequences involved in HIV-1 gag–pol and HTLV-2 gag–pro frameshifting. Using an in vitro translation system we determined frameshifting efficiencies for shuffled HIV-1/HTLV-2 RNA elements in a background of HIV-1 or HTLV-2 sequences. We show that the ability of the slippery sequence and stem–loop to promote ribosomal frameshifting is influenced by the flanking upstream sequence and the nucleotides in the spacer element. A wide range of frameshift efficiency rates was observed for both viruses when shuffling single sequence elements. The results for HIV-1/HTLV-2 chimeric constructs represent strong evidence supporting the notion that the viral wild-type sequences are not designed for maximal frameshifting activity but are optimized to a level suited to efficient viral replication.",,"['Kim, Yang-Gyun', 'Maas, Stefan', 'Rich, Alexander']",,,,
,PMC,Evaluation of the role of heterogeneous nuclear ribonucleoprotein  A1 as a host factor in murine coronavirus discontinuous transcription  and genome replication,http://dx.doi.org/10.1073/pnas.031424298,PMC30205,,,"Viruses with RNA genomes often capture and redirect host cell components to assist in mechanisms particular to RNA-dependent RNA synthesis. The nidoviruses are an order of positive-stranded RNA viruses, comprising coronaviruses and arteriviruses, that employ a unique strategy of discontinuous transcription, producing a series of subgenomic mRNAs linking a 5′ leader to distal portions of the genome. For the prototype coronavirus mouse hepatitis virus (MHV), heterogeneous nuclear ribonucleoprotein (hnRNP) A1 has been shown to be able to bind in vitro to the negative strand of the intergenic sequence, a cis-acting element found in the leader RNA and preceding each downstream ORF in the genome. hnRNP A1 thus has been proposed as a host factor in MHV transcription. To test this hypothesis genetically, we initially constructed MHV mutants with a very high-affinity hnRNP A1 binding site inserted in place of, or adjacent to, an intergenic sequence in the MHV genome. This inserted hnRNP A1 binding site was not able to functionally replace, or enhance transcription from, the intergenic sequence. This finding led us to test more directly the role of hnRNP A1 by analysis of MHV replication and RNA synthesis in a murine cell line that does not express this protein. The cellular absence of hnRNP A1 had no detectable effect on the production of infectious virus, the synthesis of genomic RNA, or the quantity or quality of subgenomic mRNAs. These results strongly suggest that hnRNP A1 is not a required host factor for MHV discontinuous transcription or genome replication.",,"['Shen, Xiaolan', 'Masters, Paul S.']",,,,
,PMC,The protective effect of childhood infections : The next challenge is to mimic safely this protection against allergy and asthma,,PMC1119618,,,,,"['Johnston, Sebastian L', 'Openshaw, Peter J M']",,,,
,PMC,A zinc finger-containing papain-like protease couples subgenomic  mRNA synthesis to genome translation in a positive-stranded  RNA virus,,PMC29352,,,"The genome expression of positive-stranded RNA viruses starts with translation rather than transcription. For some viruses, the genome is the only viral mRNA and expression is regulated primarily at the translational level and by limited proteolysis of polyproteins. Other virus groups also generate subgenomic mRNAs later in the reproductive cycle. For nidoviruses, subgenomic mRNA synthesis (transcription) is discontinuous and yields a 5′ and 3′ coterminal nested set of mRNAs. Nidovirus transcription is not essential for genome replication, which relies on the autoprocessing products of two replicase polyproteins that are translated from the genome. We now show that the N-terminal replicase subunit, nonstructural protein 1 (nsp1), of the nidovirus equine arteritis virus is in fact dispensable for replication but crucial for transcription, thereby coupling replicase expression and subgenomic mRNA synthesis in an unprecedented manner. Nsp1 is composed of two papain-like protease domains and a predicted N-terminal zinc finger, which was implicated in transcription by site-directed mutagenesis. The structural integrity of nsp1 is essential, suggesting that the protease domains form a platform for the zinc finger to operate in transcription.",,"['Tijms, Marieke A.', 'van Dinten, Leonie C.', 'Gorbalenya, Alexander E.', 'Snijder, Eric J.']",,,,
,PMC,Serological survey of parapoxvirus infection in wild ruminants in Japan in 1996-9.,,PMC2869667,,,"The prevalence of parapoxvirus infection was examined in free-ranging wild ruminants in Japan, Japanese serow (Capricornis crispus) and Japanese deer (Cervus nippon centralis), in 1996-9. We collected a total of 151 serum samples from 101 Japanese serows and 50 Japanese deer and tested for antibodies against parapoxvirus by an enzyme-linked immunosorbent assay and an agar gel immunodiffusion test. Overall seroprevalences among Japanese serows were 5/25 (20.0%) in 1996, 4/14 (28.6%) in 1997, 5/32 (15.6%) in 1998 and 2/30 (6.7%) in 1999, respectively. The seroprevalence increased with age but was not affected by sex. No antibodies were detected from any of 50 serum samples taken from Japanese deer. Our results in this study suggest that parapoxvirus infection is widespread among the population of Japanese serows, however, Japanese deer appear to be still free of the disease.",,"['Inoshima, Y.', 'Yamamoto, Y.', 'Takahashi, T.', 'Shino, M.', 'Katsumi, A.', 'Shimizu, S.', 'Sentsui, H.']",,,,
,PMC,"Ebola Virus Glycoprotein: Proteolytic Processing, Acylation, Cell Tropism, and Detection of Neutralizing Antibodies",http://dx.doi.org/10.1128/JVI.75.3.1576-1580.2001,PMC114066,,,"Using the vesicular stomatitis virus (VSV) pseudotype system, we studied the functional properties of the Ebola virus glycoprotein (GP). Amino acid substitutions at the GP cleavage site, which reduce glycoprotein cleavability and viral infectivity in some viruses, did not appreciably change the infectivity of VSV pseudotyped with GP. Likewise, removal of two acylated cysteine residues in the transmembrane region of GP showed no discernible effects on infectivity. Although most filoviruses are believed to target endothelial cells and hepatocytes preferentially, the GP-carrying VSV showed greater affinity for epithelial cells than for either of these cell types, indicating that Ebola virus GP does not necessarily have strong tropism toward endothelial cells and hepatocytes. Finally, when it was used to screen for neutralizing antibodies against Ebola virus GP, the VSV pseudotype system allowed us to detect strain-specific neutralizing activity that was inhibited by secretory GP (SGP). This finding provides evidence of shared neutralizing epitopes on GP and SGP molecules and indicates the potential of SGP to serve as a decoy for neutralizing antibodies.",,"['Ito, Hiroshi', 'Watanabe, Shinji', 'Takada, Ayato', 'Kawaoka, Yoshihiro']",,,,
,PMC,The Membrane M Protein Carboxy Terminus Binds to Transmissible Gastroenteritis Coronavirus Core and Contributes to Core Stability,http://dx.doi.org/10.1128/JVI.75.3.1312-1324.2001,PMC114037,,,"The architecture of transmissible gastroenteritis coronavirus includes three different structural levels, the envelope, an internal core, and the nucleocapsid that is released when the core is disrupted. Starting from purified virions, core structures have been reproducibly isolated as independent entities. The cores were stabilized at basic pH and by the presence of divalent cations, with Mg(2+) ions more effectively contributing to core stability. Core structures showed high resistance to different concentrations of detergents, reducing agents, and urea and low concentrations of monovalent ions (<200 mM). Cores were composed of the nucleoprotein, RNA, and the C domain of the membrane (M) protein. At high salt concentrations (200 to 300 mM), the M protein was no longer associated with the nucleocapsid, which resulted in destruction of the core structure. A specific ionic interaction between the M protein carboxy terminus and the nucleocapsid was demonstrated using three complementary approaches: (i) a binding assay performed between a collection of M protein amino acid substitution or deletion mutants and purified nucleocapsids that led to the identification of a 16-amino-acid (aa) domain (aa 237 to 252) as being responsible for binding the M protein to the nucleocapsid; (ii) the specific inhibition of this binding by monoclonal antibodies (MAbs) binding to a carboxy-terminal M protein domain close to the indicated peptide but not by MAbs specific for the M protein amino terminus; and (iii) a 26-residue peptide, including the predicted sequence (aa 237 to 252), which specifically inhibited the binding. Direct binding of the M protein to the nucleoprotein was predicted, since degradation of the exposed RNA by RNase treatment did not affect the binding. It is proposed that the M protein is embedded within the virus membrane and that the C region, exposed to the interior face of the virion in a population of these molecules, interacts with the nucleocapsid to which it is anchored, forming the core. Only the C region of the M protein is part of the core.",,"['Escors, David', 'Ortego, Javier', 'Laude, Hubert', 'Enjuanes, Luis']",,,,
,PMC,A Di-Leucine Sequence and a Cluster of Acidic Amino Acids Are  Required for Dynamic Retention in the Endosomal Recycling Compartment  of Fibroblasts,,PMC30949,,,"Insulin-regulated aminopeptidase (IRAP), a transmembrane aminopeptidase, is dynamically retained within the endosomal compartment of fibroblasts. The characteristics of this dynamic retention are rapid internalization from the plasma membrane and slow recycling back to the cell surface. These specialized trafficking kinetics result in <15% of IRAP on the cell surface at steady state, compared with 35% of the transferrin receptor, another transmembrane protein that traffics between endosomes and the cell surface. Here we demonstrate that a 29-amino acid region of IRAP's cytoplasmic domain (residues 56–84) is necessary and sufficient to promote trafficking characteristic of IRAP. A di-leucine sequence and a cluster of acidic amino acids within this region are essential elements of the motif that slows IRAP recycling. Rapid internalization requires any two of three distinct motifs: M(15,16), DED(64–66), and LL(76,77). The DED and LL sequences are part of the motif that regulates recycling, demonstrating that this motif is bifunctional. In this study we used horseradish peroxidase quenching of fluorescence to demonstrate that IRAP is dynamically retained within the transferrin receptor-containing general endosomal recycling compartment. Therefore, our data demonstrate that motifs similar to those that determine targeting among distinct membrane compartments can also regulate the rate of transport of proteins from endosomal compartments. We propose a model for dynamic retention in which IRAP is transported from the general endosomal recycling compartment in specialized, slowly budding recycling vesicles that are distinct from those that mediate rapid recycling back to the surface (e.g., transferrin receptor-containing transport vesicles). It is likely that the dynamic retention of IRAP is an example of a general mechanism for regulating the distribution of proteins between the surface and interior of cells.",,"['Johnson, Amy O.', 'Lampson, Michael A.', 'McGraw, Timothy E.']",,,,
,PMC,Programmed +1 frameshifting stimulated by complementarity between a downstream mRNA sequence and an error-correcting region of rRNA.,,PMC1370085,,,"Like most retroviruses and retrotransposons, the retrotransposon Ty3 expresses its pol gene analog (POL3) as a translational fusion to the upstream gag analog (GAG3). The Gag3-Pol3 fusion occurs by frameshifting during translation of the mRNA that encodes the two separate but overlapping ORFs. We showed previously that the shift occurs by out-of-frame binding of a normal aminoacyl-tRNA in the ribosomal A site caused by an aberrant codonoanticodon interaction in the P site. This event is unlike all previously described programmed translational frameshifts because it does not require tRNA slippage between cognate or near-cognate codons in the mRNA. A sequence of 15 nt distal to the frameshift site stimulates frameshifting 7.5-fold. Here we show that the Ty3 stimulator acts as an unstructured region to stimulate frameshifting. Its function depends on strict spacing from the site of frameshifting. Finally, the stimulator increases frameshifting dependent on sense codon-induced pausing, but has no effect on frameshifting dependent on pauses induced by nonsense codons. Complementarity between the stimulator and a portion of the accuracy center of the ribosome, Helix 18, implies that the stimulator may directly disrupt error correction by the ribosome.",,"['Li, Z', 'Stahl, G', 'Farabaugh, P J']",,,,
,PMC,"Prospective study of the incidence, aetiology and outcome of adult lower respiratory tract illness in the community",http://dx.doi.org/10.1136/thorax.56.2.109,PMC1746009,,,"BACKGROUND—Acute lower respiratory tract illness in previously well adults is usually labelled as acute bronchitis and treated with antibiotics without establishing the aetiology. Viral infection is thought to be the cause in most cases. We have investigated the incidence, aetiology, and outcome of this condition.
METHODS—Previously well adults from a stable suburban population consulting over one year with a lower respiratory tract illness were studied. For the first six months detailed investigations identified predetermined direct and indirect markers of infection. Evidence of infection was assessed in relation to presenting clinical features, indirect markers of infection, antibiotic use, and outcome.
RESULTS—Consultations were very common, particularly in younger women (70/1000 per year in previously well women aged 16-39 years), mainly in the winter months; 638 patients consulted, of whom 316were investigated. Pathogens were identified in 173 (55%) cases: bacteria in 82 (Streptococcus pneumoniae 54, Haemophilus influenzae 31, Moraxella catarrhalis 7), atypical organisms in 75 (Chlamydia pneumoniae 55, Mycoplasma pneumoniae 23), and viruses in 61 (influenza 23). Seventy nine (24%) had indirect evidence of infection. Bacterial and atypical infection correlated with changes in the chest radiograph and high levels of C reactive protein but not with (a) the GP's clinical assessment of whether infection was present, (b) clinical features other than focal chest signs, and (c) outcome, whether or not appropriate antibiotics were prescribed.
CONCLUSIONS—Over 50% of patients have direct and/or indirect evidence of infection, most commonly bacterial and atypical pathogens, but the outcome is unrelated to the identified pathogens. Many patients improve without antibiotics and investigations do not help in the management of these patients. GPs can reassure patients of the causes and usual outcome of this self-limiting condition.",,"['Macfarlane, J', 'Holmes, W', 'Gard, P', 'Macfarlane, R', 'Rose, D', 'Weston, V', 'Leinonen, M', 'Saikku, P', 'Myint, S']",,,,
,PMC,In situ hybridization for the detection of transmissible gastroenteritis virus in pigs and comparison with other methods.,,PMC1189639,,,"Archived formalin-fixed, paraffin-embedded tissues from 25 pigs naturally infected with transmissible gastroenteritis virus (TGEV) were examined by in situ hybridization for TGEV nucleic acid using a nonradioactive digoxigenin-labeled cDNA probe that targeted the nucleocapsid sequence of TGEV strains. The results of in situ hybridization for the detection of TGEV were compared with virus isolation (VI), a fluorescent antibody test (FAT), and transmission electron microscopy (TEM). VI, FAT, and TEM were tested over a course of time before the in situ hybridization was performed. Positive hybridization signals were detected in duodenal, jejunal, and ileal enterocytes from 21 pigs. Hybridization signals were confined to the cytoplasm. Intestinal specimens from 25 piglets were evaluated by 4 tests. Twenty-one of 25 were positive by in situ hybridization. Of these 21 samples, 5 (24%) were positive for TGEV by all 4 tests, 15 (71%) were positive by FAT, 14 (67%) were positive by VI, and 6 (29%) were positive by TEM. In situ hybridization for the detection of TGEV in formalin-fixed, paraffin-embedded tissues provides a rapid means of confirmation of a histopathological diagnosis of TGEV without virus isolation, or when only formalin-fixed intestinal specimens were available.",,"['Kim, B', 'Chae, C']",,,,
,PMC,Efficacy of a transmissible gastroenteritis coronavirus with an altered ORF-3 gene.,,PMC1189638,,,Serial passage of virulent transmissible gastroenteritis virus through cell culture reduced its virulence in 3-day-old piglets. Intramuscular inoculation of pregnant gilts with 2 doses of this modified-live virus elicited a level of lactogenic immunity that protected their nursing piglets against a lethal dose of challenge virus. Sequence analysis of a 637-bp fragment of the spike gene containing most of the aminopeptidase receptor and the 4 major antigenic sites from the original and the serially passed viruses were nearly identical. Gel analysis revealed that the fragment from the ORF-3 gene of virulent virus was smaller than the corresponding fragment from the serially passed virus. Sequence analysis of the fragment from the passed virus revealed that the sequence between nt 5310 and nt 5434 was replaced by a 636-bp fragment from the polymerase 1A gene. This replacement resulted in the loss of the CTAAACTT leader RNA-binding site and ATG start codon for the ORF-3A gene but it did not affect the ORF-3B gene.,,"Woods, R D",,,,
,PMC,"Diagnosis of Noncultivatable Gastroenteritis Viruses, the Human Caliciviruses",http://dx.doi.org/10.1128/CMR.14.1.15-37.2001,PMC88960,,,"Gastroenteritis is one of the most common illnesses of humans, and many different viruses have been causally associated with this disease. Of those enteric viruses that have been established as etiologic agents of gastroenteritis, only the human caliciviruses cannot be cultivated in vitro. The cloning of Norwalk virus and subsequently of other human caliciviruses has led to the development of several new diagnostic assays. Antigen detection enzyme immunoassays (EIAs) using polyclonal hyperimmune animal sera and antibody detection EIAs using recombinant virus-like particles have supplanted the use of human-derived reagents, but the use of these assays has been restricted to research laboratories. Reverse transcription-PCR assays for the detection of human caliciviruses are more widely available, and these assays have been used to identify virus in clinical specimens as well as in food, water, and other environmental samples. The application of these newer assays has significantly increased the recognition of the importance of human caliciviruses as causes of sporadic and outbreak-associated gastroenteritis.",,"['Atmar, Robert L.', 'Estes, Mary K.']",,,,
,PMC,Single-Tube Single-Enzyme Reverse Transcriptase PCR Assay for Detection of Bovine Viral Diarrhea Virus in  Pooled Bovine Serum,http://dx.doi.org/10.1128/JCM.39.1.343-346.2001,PMC87727,,,"A reverse transcriptase PCR (RT-PCR) was developed for use as a diagnostic screening test for the detection of bovine viral diarrhea virus (BVDV) in pooled bovine serum samples. Individual serum samples from 60 dairy cattle herds located in Pennsylvania were evaluated by the microplate virus isolation method, and pooled sera were analyzed by RT-PCR. RT-PCR was sensitive and specific and detected a single viremic serum sample in up to 100 pooled serum samples. RT-PCR analysis of pooled sera provides a rapid and cost-effective method for the screening of cattle herds for the presence of animals persistently infected with BVDV.",,"['Weinstock, Daniel', 'Bhudevi, Bodreddigari', 'Castro, Anthony E.']",,,,
,PMC,Outbreak of Necrotizing Enterocolitis Associated with  Enterobacter sakazakii in Powdered Milk Formula,http://dx.doi.org/10.1128/JCM.39.1.293-297.2001,PMC87717,,,"We describe an outbreak of necrotizing enterocolitis (NEC) that occurred in the neonatal intensive care unit of our hospital. A total of 12 neonates developed NEC in June-July 1998. For two of them, twin brothers, the NEC turned out to be fatal. Enterobacter sakazakii, a known contaminant of powdered milk formula, was isolated from a stomach aspirate, anal swab, and/or blood sample for 6 of the 12 neonates. A review of feeding procedures revealed that 10 of the 12 patients were fed orally with the same brand of powdered milk formula. E. sakazakii was isolated from the implicated prepared formula milk as well as from several unopened cans of a single batch. Molecular typing by arbitrarily primed PCR (AP-PCR) confirmed, although partially, strain similarity between milk and patient isolates. No further cases of NEC were observed after the use of the contaminated milk formula was stopped. With this outbreak we show that intrinsic microbiological contamination of powdered milk formula can be a possible contributive factor in the development of NEC, a condition encountered almost exclusively in formula-fed premature infants. The use of sterilized liquid milk formula in neonatal care could prevent problems with intrinsic and extrinsic contamination of powdered milk formula.",,"['van Acker, Jos', 'de Smet, Francis', 'Muyldermans, Gaëtan', 'Bougatef, Adel', 'Naessens, Anne', 'Lauwers, Sabine']",,,,
,PMC,Simultaneous Detection of Influenza Viruses A and B Using Real-Time Quantitative PCR,http://dx.doi.org/10.1128/JCM.39.1.196-200.2001,PMC87701,,,"Since influenza viruses can cause severe illness, timely diagnosis is important for an adequate intervention. The available rapid detection methods either lack sensitivity or require complex laboratory manipulation. This study describes a rapid, sensitive detection method that can be easily applied to routine diagnosis. This method simultaneously detects influenza viruses A and B in specimens of patients with respiratory infections using a TaqMan-based real-time PCR assay. Primers and probes were selected from highly conserved regions of the matrix protein gene of influenza virus A and the hemagglutinin gene segment of influenza virus B. The applicability of this multiplex PCR was evaluated with 27 influenza virus A and 9 influenza virus B reference strains and isolates. In addition, the specificity of the assay was assessed using eight reference strains of other respiratory viruses (parainfluenza viruses 1 to 3, respiratory syncytial virus Long strain, rhinoviruses 1A and 14, and coronaviruses OC43 and 229E) and 30 combined nose and throat swabs from asymptomatic subjects. Electron microscopy-counted stocks of influenza viruses A and B were used to develop a quantitative PCR format. Thirteen copies of viral RNA were detected for influenza virus A, and 11 copies were detected for influenza virus B, equaling 0.02 and 0.006 50% tissue culture infective doses, respectively. The diagnostic efficacy of the multiplex TaqMan-based PCR was determined by testing 98 clinical samples. This real-time PCR technique was found to be more sensitive than the combination of conventional viral culturing and shell vial culturing.",,"['van Elden, L. J. R.', 'Nijhuis, M.', 'Schipper, P.', 'Schuurman, R.', 'van Loon, A. M.']",,,,
,PMC,Pathogenesis of Primary Respiratory Disease Induced by Isolates from a New Genetic Cluster of Bovine  Viral Diarrhea Virus Type I,http://dx.doi.org/10.1128/JCM.39.1.146-153.2001,PMC87694,,,"The pathogenesis of infection induced by cytopathogenic isolates from the newly identified genetic cluster Id of bovine viral diarrhea virus (BVDV) type I was studied in two experimental infections of previously seronegative, immunocompetent calves. Experiment 1 focused on the evaluation of clinical patterns, viremia, and serological responses. All infected calves in this experiment developed respiratory symptoms and seroconverted to BVDV positivity. Contact calves also contracted a respiratory tract infection following exposure to infected animals. Viremia was demonstrated between postinfection days 2 and 17, and the virus was detected in organ specimens of all but one each of the infected and contact calves. In experiment 2, the distribution of BVDV in various tissues of calves euthanized at defined days postinfection was studied. In two of these calves recurrent shedding of BVDV in nasal secretions was shown. BVDV was detected in various tissues of all infected calves throughout the experiment and also following seroconversion and the clearance of BVDV from the circulatory system. Despite the widespread distribution of the virus in various organs, significant tissue damage was found mainly in respiratory tract and lymphoid tissues. These experiments revealed that viruses from cluster Id of BVDV are able to induce primary respiratory disease in previously seronegative, immunocompetent calves. Contact transmission and virus recurrence, contrary to observations from acute experimental infections with noncytopathogenic BVDV, are likely to reflect differences in biological features of these cytopathogenic isolates. Virus shedding and its presence in tissues following peripheral clearance and in the presence of antibodies may have implications in the diagnosis, pathogenesis, and epidemiology of BVDV-induced syndromes in cattle.",,"['Baule, C.', 'Kulcsár, G.', 'Belák, K.', 'Albert, M.', 'Mittelholzer, C.', 'Soós, T.', 'Kucsera, L.', 'Belák, S.']",,,,
,PMC,Early Detection of Acute Rhinovirus Infections by a Rapid Reverse Transcription-PCR Assay,http://dx.doi.org/10.1128/JCM.39.1.129-133.2001,PMC87691,,,"The development of a rhinovirus (RV)-RNA-specific reverse transcription (RT)-PCR assay is complicated by the close homology between the RV and enterovirus (EV) genomes in the highly conserved 5′-noncoding region, which is chosen for primer design in most RT-PCR assays. We have developed a sensitive, rapid, and RV-specific nested RT-PCR assay and have used it to test nasopharyngeal aspirates from 556 patients presenting with acute respiratory tract infections. RV RNA was detected by nested RT-PCR not only in all of 52 samples that were RV positive by virus isolation methods but also in 124 of 367 samples that were negative by virus isolation methods and enzyme-linked immunosorbent assay (ELISA). In addition, in 23 of 137 samples that were positive for a different respiratory virus by virus isolation and/or ELISA, RV RNA was detected by RT-PCR. EVs, adenoviruses, respiratory syncytial viruses, coronaviruses, and influenza and parainfluenza viruses, including clinical isolates as well as stock viruses, were not amplified in our RV-specific RT-PCR assay, indicating that this assay was highly specific. The processing time was less than 2 days for the RT-PCR, as opposed to up to 2 weeks for virus isolation. These results indicate that nested RT-PCR is more sensitive than conventional methods for the detection of RV in patients experiencing acute respiratory tract infections and represents the only reliable tool for the early laboratory diagnosis of RV infections. This is especially important in light of new opportunities for therapy currently being developed.",,"['Steininger, Christoph', 'Aberle, Stephan W.', 'Popow-Kraupp, Theresia']",,,,
,PMC,Respiratory Viral Infections among Pediatric Inpatients and Outpatients in Taiwan from 1997 to 1999,http://dx.doi.org/10.1128/JCM.39.1.111-118.2001,PMC87689,,,"The present study examined the association of specific virus infections with acute respiratory tract conditions among hospitalized and outpatient children in a subtropical country. A total of 2,295 virus infections were detected in 6,986 patients between 1997 and 1999, including infections caused by respiratory syncytial virus (RSV) (1.7%), parainfluenza virus (2.0%), influenza B virus (2.6%), adenovirus (4.0%), herpes simplex virus type 1 (4.4%), influenza A virus (5.5%), and enterovirus (12.7%). There were 61 mixed infections, and no consistent seasonal variation was found. One or more viruses were detected among 24.8% of hospitalized patients and 35.0% of outpatients. The frequencies and profiles of detection of various viruses among in- and outpatients were different. The occurrence of enterovirus infections exceeded that of other viral infections detected in 1998 and 1999 due to outbreaks of enterovirus 71 and coxsackievirus A10. RSV was the most prevalent virus detected among hospitalized children, whereas influenza virus was the most frequently isolated virus in the outpatient group. Most respiratory viral infections (39.3%) occurred in children between 1 and 3 years old. RSV (P < 0.025) and influenza A virus (P < 0.05) infections were dominant in the male inpatient group. In addition, most pneumonia and bronchiolitis (48.4%) was caused by RSV among hospitalized children less than 6 months old. Adenovirus was the most common agent associated with pharyngitis and tonsilitis (45.5%). These data expand our understanding of the etiology of acute respiratory tract viral infections among in- and outpatients in a subtropical country and may contribute to the prevention and control of viral respiratory tract infections.",,"['Tsai, Huey-Pin', 'Kuo, Pin-Hwa', 'Liu, Ching-Chuan', 'Wang, Jen-Ren']",,,,
,PMC,Sialic Acid Binding Activity of Transmissible Gastroenteritis Coronavirus Affects Sedimentation Behavior of Virions and Solubilized Glycoproteins,http://dx.doi.org/10.1128/JVI.75.2.844-849.2001,PMC113980,,,"The sedimentation behavior of transmissible gastroenteritis coronavirus (TGEV) was analyzed. Upon sucrose gradient centrifugation, the major virus band was found at a density of 1.20 to 1.22 g/cm(3). This high density was observed only when TGEV with a functional sialic acid binding activity was analyzed. Mutants of TGEV that lacked sialic acid binding activity due to a point mutation in the sialic acid binding site of the S protein were mainly recovered at a lower-density position on the sucrose gradient (1.18 to 1.19 g/cm(3)). Neuraminidase treatment of purified virions resulted in a shift of the sedimentation value from the higher to the lower density. These results suggest that binding of sialoglycoproteins to the virion surface is responsible for the sedimentation behavior of TGEV. When purified virions were treated with octylglucoside to solubilize viral glycoproteins, ultracentrifugation resulted in sedimentation of the S protein of TGEV. However, when neuraminidase-treated virions or mutants with a defective sialic acid binding activity were analyzed, the S protein remained in the supernatant rather than in the pellet fraction. These results indicate that the interaction of the surface protein S with sialoglycoconjugates is maintained after solubilization of this viral glycoprotein by detergent treatment.",,"['Krempl, Christine', 'Herrler, Georg']",,,,
,PMC,Identification of Key Residues in Subgroup A Avian Leukosis Virus Envelope Determining Receptor Binding Affinity and Infectivity of Cells Expressing Chicken or Quail Tva Receptor,http://dx.doi.org/10.1128/JVI.75.2.726-737.2001,PMC113969,,,"To better understand retroviral entry, we have characterized the interactions between subgroup A avian leukosis virus [ALV(A)] envelope glycoproteins and Tva, the receptor for ALV(A), that result in receptor interference. We have recently shown that soluble forms of the chicken and quail Tva receptor (sTva), expressed from genes delivered by retroviral vectors, block ALV(A) infection of cultured chicken cells (∼200-fold antiviral effect) and chickens (>98% of the birds were not infected). We hypothesized that inhibition of viral replication by sTva would select virus variants with mutations in the surface glycoprotein (SU) that altered the binding affinity of the subgroup A SU for the sTva protein and/or altered the normal receptor usage of the virus. Virus propagation in the presence of quail sTva-mIgG, the quail Tva extracellular region fused to the constant region of the mouse immunoglobulin G (IgG) protein, identified viruses with three mutations in the subgroup A hr1 region of SU, E149K, Y142N, and Y142N/E149K. These mutations reduced the binding affinity of the subgroup A envelope glycoproteins for quail sTva-mIgG (32-, 324-, and 4,739-fold, respectively) but did not alter their binding affinity for chicken sTva-mIgG. The ALV(A) mutants efficiently infected cells expressing the chicken Tva receptor but were 2-fold (E149K), 10-fold (Y142N), and 600-fold (Y142N/E149K) less efficient at infecting cells expressing the quail Tva receptor. These mutations identify key determinants of the interaction between the ALV(A) glycoproteins and the Tva receptor. We also conclude from these results that, at least for the wild-type and variant ALV(A)s tested, the receptor binding affinity was directly related to infection efficiency.",,"['Holmen, Sheri L.', 'Melder, Deborah C.', 'Federspiel, Mark J.']",,,,
,PMC,The Coronavirus Infectious Bronchitis Virus Nucleoprotein Localizes to the Nucleolus,http://dx.doi.org/10.1128/JVI.75.1.506-512.2001,PMC113943,,,The coronavirus nucleoprotein (N) has been reported to be involved in various aspects of virus replication. We examined by confocal microscopy the subcellular localization of the avian infectious bronchitis virus N protein both in the absence and in the context of an infected cell and found that N protein localizes both to the cytoplasmic and nucleolar compartments.,,"['Hiscox, Julian A.', 'Wurm, Torsten', 'Wilson, Louise', 'Britton, Paul', 'Cavanagh, David', 'Brooks, Gavin']",,,,
,PMC,cis-Acting Sequences Required for Coronavirus Infectious Bronchitis Virus Defective-RNA Replication and Packaging,http://dx.doi.org/10.1128/JVI.75.1.125-133.2001,PMC113905,,,"The parts of the RNA genome of infectious bronchitis virus (IBV) required for replication and packaging of the RNA were investigated using deletion mutagenesis of a defective RNA (D-RNA) CD-61 (6.1 kb) containing a chloramphenicol acetyltransferase reporter gene. A D-RNA with the first 544, but not as few as 338, nucleotides (nt) of the 5′ terminus was replicated; the 5′ untranslated region (UTR) comprises 528 nt. Region I of the 3′ UTR, adjacent to the nucleocapsid protein gene, comprised 212 nt and could be removed without impairment of replication or packaging of D-RNAs. A D-RNA with the final 338 nt, including the 293 nt in the highly conserved region II of the 3′ UTR, was replicated. Thus, the 5′-terminal 544 nt and 3′-terminal 338 nt contained the necessary signals for RNA replication. Phylogenetic analysis of 19 strains of IBV and 3 strains of turkey coronavirus predicted a conserved stem-loop structure at the 5′ end of region II of the 3′ UTR. Removal of the predicted stem-loop structure abolished replication of the D-RNAs. D-RNAs in which replicase gene 1b-derived sequences had been removed or replaced with all the downstream genes were replicated well but were rescued poorly, suggesting inefficient packaging. However, no specific part of the 1b gene was required for efficient packaging.",,"['Dalton, Kevin', 'Casais, Rosa', 'Shaw, Kathy', 'Stirrups, Kathleen', 'Evans, Sharon', 'Britton, Paul', 'Brown, T. David K.', 'Cavanagh, Dave']",,,,
,PMC,VIDA: a virus database system  for the organization of animal virus genome open reading frames,,PMC29831,,,"VIDA is a new virus database that organizes open reading frames (ORFs) from partial and complete genomic sequences from animal viruses. Currently VIDA includes all sequences from GenBank for Herpesviridae, Coronaviridae and Arteriviridae. The ORFs are organized into homologous protein families, which are identified on the basis of sequence similarity relationships. Conserved sequence regions of potential functional importance are identified and can be retrieved as sequence alignments. We use a controlled taxonomical and functional classification for all the proteins and protein families in the database. When available, protein structures that are related to the families have also been included. The database is available for online search and sequence information retrieval at http://www.biochem.ucl.ac.uk/bsm/virus_database/VIDA.html.",,"['Albà, M. Mar', 'Lee, David', 'Pearl, Frances\n M. G.', 'Shepherd, Adrian\n J.', 'Martin, Nigel', 'Orengo, Christine\n A.', 'Kellam, Paul']",,,,
,PMC,"Viral myocarditis and dilated cardiomyopathy: mechanisms, manifestations, and management",http://dx.doi.org/10.1136/pmj.77.903.4,PMC1741887,,,"Viral infection of the heart is relatively common and usually of little consequence. It can, however, lead to substantial cardiac damage and severe acute heart failure. It can also evolve into the progressive syndrome of chronic heart failure. Recent studies have gone some way towards unravelling the complex mechanisms underlying the heart muscle damage that occurs after viral infection. These studies have lent support to both immune and viral mediated (independent of an immune response) cardiac damage. Acute myocarditis can present in various ways, and it may be a cause of sudden death in an otherwise healthy young adult. New treatments for viral heart disease are awaited. In the meanwhile, the haemodynamic support of patients with acute left ventricular failure caused by myocarditis should be aggressive, to allow for the possibility of spontaneous recovery. Contemporary trials of treatment in chronic heart failure secondary to dilated cardiomyopathy support the use of angiotensin converting enzyme inhibitors, β adrenoceptor blockers, and spironolactone in such patients.


Keywords: myocarditis; heart failure; coxsackie B virus; dilated cardiomyopathy",,"['Kearney, M', 'Cotton, J', 'Richardson, P', 'Shah, A']",,,,
,PMC,Correlation of Susceptibility of Immature Mice to Fungal Infection (Blastomycosis) and Effector Cell Function,,PMC97787,,,"Immature mice are highly susceptible to blastomycosis, which is similar to other mycoses and has parallels in humans. The murine susceptibility is noteworthy in that it persists beyond the development of resistance to other, nonfungal pathogens and the maturation of most immune functions. As the susceptibility to blastomycosis appeared to be related to an early event after infection, primary effector cell function was studied. We found that peritoneal inflammatory cells, enriched for neutrophils, from immature (3-week-old) mice killed nonphagocytizable Blastomyces dermatitidis cells less (25%) than did cells from mature (8-week) mice (70%) (P < 0.01), a defect intrinsic to the neutrophils. This correlated with an impaired immature cell oxidative burst. Killing of phagocytizable Candida albicans was not significantly different, 73 versus 87%. Thioglycolate-elicited cells were more impaired; killing of B. dermatitidis was insignificant, and killing of C. albicans was more impaired in immature (16% killing) than in mature (45%) cells (P < 0.02). Peripheral blood neutrophils from mature animals killed B. dermatitidis (41%) more than did those from immature animals (10%) (P < 0.02); C. albicans was killed efficiently by both. Resting or activated peritoneal macrophages from both types of animals showed no differences in B. dermatitidis killing. These results suggest that the susceptibility of immature mice is related at least in part to the depressed capacity of their neutrophils to kill B. dermatitidis.",,"['Ganer, Ari', 'Brummer, Elmer', 'Stevens, David A.']",,,,
,PMC,Characterization of a Coronavirus Isolated from a Diarrheic Foal,,PMC87631,,,"A coronavirus was isolated from feces of a diarrheic foal and serially propagated in human rectal adenocarcinoma (HRT-18) cells. Antigenic and genomic characterizations of the virus (isolate NC99) were based on serological comparison with other avian and mammalian coronaviruses and sequence analysis of the nucleocapsid (N) protein gene. Indirect fluorescent-antibody assay procedures and virus neutralization assays demonstrated a close antigenic relationship with bovine coronavirus (BCV) and porcine hemagglutinating encephalomyelitis virus (mammalian group 2 coronaviruses). Using previously described BCV primers, the N protein gene of isolate NC99 was amplified by a reverse transcriptase PCR (RT-PCR) procedure. The RT-PCR product was cloned into pUC19 and sequenced; the complete N protein of NC99 (446 amino acids) was then compared with published N protein sequences of other avian and mammalian coronaviruses. A high degree of identity (89.0 to 90.1%) was observed between the N protein sequence of NC99 and published sequences of BCV (Mebus and F15 strains) and human coronavirus (strain OC43); only limited identity (<25%) was observed with group 1 and group 3 coronaviruses. Based on these findings, the virus has been tentatively identified as equine coronavirus (ECV). ECV NC99 was determined to have close antigenic and/or genetic relationships with mammalian group 2 coronaviruses, thus identifying it as a member of this coronavirus antigenic group.",,"['Guy, James S.', 'Breslin, Jamie J.', 'Breuhaus, Babetta', 'Vivrette, Sally', 'Smith, Lynda G.']",,,,
,PMC,"DNA-Directed Expression of Functional Flock House Virus RNA1 Derivatives in Saccharomyces cerevisiae, Heterologous Gene Expression, and Selective Effects on  Subgenomic mRNA Synthesis",,PMC112455,,,"Flock house virus (FHV), a positive-strand RNA animal virus, is the only higher eukaryotic virus shown to undergo complete replication in yeast, culminating in production of infectious virions. To facilitate studies of viral and host functions in FHV replication in Saccharomyces cerevisiae, yeast DNA plasmids were constructed to inducibly express wild-type FHV RNA1 in vivo. Subsequent translation of FHV replicase protein A initiated robust RNA1 replication, amplifying RNA1 to levels approaching those of rRNA, as in FHV-infected animal cells. The RNA1-derived subgenomic mRNA, RNA3, accumulated to even higher levels of >100,000 copies per yeast cell, compared to 10 copies or less per cell for 95% of yeast mRNAs. The time course of RNA1 replication and RNA3 synthesis in induced yeast paralleled that in yeast transfected with natural FHV virion RNA. As in animal cells, RNA1 replication and RNA3 synthesis depended on FHV RNA replicase protein A and 3′-terminal RNA1 sequences but not viral protein B2. Additional plasmids were engineered to inducibly express RNA1 derivatives with insertions of the green fluorescent protein (GFP) gene in subgenomic RNA3. These RNA1 derivatives were replicated, synthesized RNA3, and expressed GFP when provided FHV polymerase in either cis or trans, providing the first demonstration of reporter gene expression from FHV subgenomic RNA. Unexpectedly, fusing GFP to the protein A C terminus selectively inhibited production of positive- and negative-strand subgenomic RNA3 but not genomic RNA1 replication. Moreover, changing the first nucleotide of the subgenomic mRNA from G to T selectively inhibited production of positive-strand but not negative-strand RNA3, suggesting that synthesis of negative-strand subgenomic RNA3 may precede synthesis of positive-strand RNA3.",,"['Price, B. Duane', 'Roeder, Mark', 'Ahlquist, Paul']",,,,
,PMC,Genetic Manipulation of Arterivirus Alternative mRNA Leader-Body Junction Sites Reveals Tight Regulation of Structural Protein Expression,,PMC112446,,,"To express its structural proteins, the arterivirus Equine arteritis virus (EAV) produces a nested set of six subgenomic (sg) RNA species. These RNA molecules are generated by a mechanism of discontinuous transcription, during which a common leader sequence, representing the 5′ end of the genomic RNA, is attached to the bodies of the sg RNAs. The connection between the leader and body parts of an mRNA is formed by a short, conserved sequence element termed the transcription-regulating sequence (TRS), which is present at the 3′ end of the leader as well as upstream of each of the structural protein genes. With the exception of RNA3, only one body TRS was previously assumed to be used to join the leader and body of each EAV sg RNA. Here we show that for the synthesis of two other sg RNAs, RNA4 and RNA5, alternative leader-body junction sites that differ substantially in transcriptional activity are used. By site-directed mutagenesis of an EAV infectious cDNA clone, the alternative TRSs used to generate RNA3, -4, and -5 were inactivated, which strongly influenced the corresponding RNA levels and the production of infectious progeny virus. The relative amounts of RNA produced from alternative TRSs differed significantly and corresponded to the relative infectivities of the virus mutants. This strongly suggested that the structural proteins that are expressed from these RNAs are limiting factors during the viral life cycle and that the discontinuous step in sg RNA synthesis is crucial for the regulation of their expression. On the basis of a theoretical analysis of the predicted RNA structure of the 3′ end of the EAV genome, we propose that the local secondary RNA structure of the body TRS regions is an important factor in the regulation of the discontinuous step in EAV sg mRNA synthesis.",,"['Pasternak, Alexander O.', 'Gultyaev, Alexander P.', 'Spaan, Willy J. M.', 'Snijder, Eric J.']",,,,
,PMC,Influenza Virus Matrix Protein Is the Major Driving  Force in Virus Budding,,PMC112434,,,"To get insights into the role played by each of the influenza A virus polypeptides in morphogenesis and virus particle assembly, the generation of virus-like particles (VLPs) has been examined in COS-1 cell cultures expressing, from recombinant plasmids, different combinations of the viral structural proteins. The presence of VLPs was examined biochemically, following centrifugation of the supernatants collected from transfected cells through sucrose cushions and immunoblotting, and by electron-microscopic analysis. It is demonstrated that the matrix (M1) protein is the only viral component which is essential for VLP formation and that the viral ribonucleoproteins are not required for virus particle formation. It is also shown that the M1 protein, when expressed alone, assembles into virus-like budding particles, which are released in the culture medium, and that the recombinant M1 protein accumulates intracellularly, forming tubular structures. All these results are discussed with regard to the roles played by the virus polypeptides during virus assembly.",,"['Gómez-Puertas, Paulino', 'Albo, Carmen', 'Pérez-Pastrana, Esperanza', 'Vivo, Amparo', 'Portela, Agustín']",,,,
,PMC,Intracellular Hepadnavirus Nucleocapsids Are Selected for Secretion by Envelope Protein-Independent Membrane Binding,,PMC112426,,,"Hepadnaviruses are DNA viruses but, as pararetroviruses, their morphogenesis initiates with the encapsidation of an RNA pregenome, and these viruses have therefore evolved mechanisms to exclude nucleocapsids that contain incompletely matured genomes from participating in budding and secretion. We provide here evidence that binding of hepadnavirus core particles from the cytosol to their target membranes is a distinct step in morphogenesis, discriminating among different populations of intracellular capsids. Using the duck hepatitis B virus (DHBV) and a flotation assay, we found about half of the intracellular capsids to be membrane associated due to an intrinsic membrane-binding affinity. In contrast to free cytosolic capsids, this subpopulation contained largely mature, double-stranded DNA genomes and lacked core protein hyperphosphorylation, both features characteristic for secreted virions. Against expectation, however, the selective membrane attachment observed did not require the presence of the large DHBV envelope protein, which has been considered to be crucial for nucleocapsid-membrane interaction. Furthermore, removal of surface-exposed phosphate residues from nonfloating capsids by itself did not suffice to confer membrane affinity and, finally, hyperphosphorylation was absent from nonenveloped nucleocapsids that were released from DHBV-transfected cells. Collectively, these observations argue for a model in which nucleocapsid maturation, involving the viral genome, capsid structure, and capsid dephosphorylation, leads to the exposure of a membrane-binding signal as a step crucial for selecting the matured nucleocapsid to be incorporated into the capsid-independent budding of virus particles.",,"['Mabit, Hélène', 'Schaller, Heinz']",,,,
,PMC,Specific Secretion of Active Single-Chain Fv Antibodies  into the Supernatants of Escherichia coli Cultures  by Use of the Hemolysin System,,PMC92415,,,"A simple method for the nontoxic, specific, and efficient secretion of active single-chain Fv antibodies (scFvs) into the supernatants of Escherichia coli cultures is reported. The method is based on the well-characterized hemolysin transport system (Hly) of E. coli that specifically secretes the target protein from the bacterial cytoplasm into the extracellular medium without a periplasmic intermediate. The culture media that accumulate these Hly-secreted scFv's can be used in a variety of immunoassays without purification. In addition, these culture supernatants are stable over long periods of time and can be handled basically as immune sera.",,"['Fernández, Luis A.', 'Sola, Isabel', 'Enjuanes, Luis', 'de Lorenzo, Víctor']",,,,
,PMC,Streptococcus pneumoniae and Mycoplasma pneumoniae coinfection in community acquired pneumonia,http://dx.doi.org/10.1136/adc.83.5.413,PMC1718558,,,The characteristics of nine children with community acquired pneumonia with evidence of Streptococcus pneumoniae and Mycoplasma pneumoniae coinfection are described.,,"['Toikka, P', 'Juven, T', 'Virkki, R', 'Leinonen, M', 'Mertsola, J', 'Ruuskanen, O']",,,,
,PMC,Abstracts,,PMC312880,,,,,,,,,
,PMC,Nitric oxide and virus infection,http://dx.doi.org/10.1046/j.1365-2567.2000.00142.x,PMC2327086,,,"Nitric oxide (NO) has complex and diverse functions in physiological and pathophysiological phenomena. The mechanisms of many events induced by NO are now well defined, so that a fundamental understanding of NO biology is almost established. Accumulated evidence suggests that NO and oxygen radicals such as superoxide are key molecules in the pathogenesis of various infectious diseases. NO biosynthesis, particularly through expression of an inducible NO synthase (iNOS), occurs in a variety of microbial infections. Although antimicrobial activity of NO is appreciated for bacteria and protozoa, NO has opposing effects in virus infections such as influenza virus pneumonia and certain other neurotropic virus infections. iNOS produces an excessive amount of NO for long periods, which allows generation of a highly reactive nitrogen oxide species, peroxynitrite, via a radical coupling reaction of NO with superoxide. Thus, peroxynitrite causes oxidative tissue injury through potent oxidation and nitration reactions of various biomolecules. NO also appears to affect a host's immune response, with immunopathological consequences. For example, overproduction of NO in virus infections in mice is reported to suppress type 1 helper T-cell-dependent immune responses, leading to type 2 helper T-cell-biased immunological host responses. Thus, NO may be a host response modulator rather than a simple antiviral agent. The unique biological properties of NO are further illustrated by our recent data suggesting that viral mutation and evolution may be accelerated by NO-induced oxidative stress. Here, we discuss these multiple roles of NO in pathogenesis of virus infections as related to both non-specific inflammatory responses and immunological host reactions modulated by NO during infections in vivo.",,"['Akaike, T', 'Maeda, H']",,,,
,PMC,Toxoplasma gondii: from animals to humans,,PMC3109627,,,"Toxoplasmosis is one of the more common parasitic zoonoses world-wide. Its causative agent, Toxoplasma gondii, is a facultatively heteroxenous, polyxenous protozoon that has developed several potential routes of transmission within and between different host species. If first contracted during pregnancy, T. gondii may be transmitted vertically by tachyzoites that are passed to the foetus via the placenta. Horizontal transmission of T. gondii may involve three life-cycle stages, i.e. ingesting infectious oocysts from the environment or ingesting tissue cysts or tachyzoites which are contained in meat or primary offal (viscera) of many different animals. Transmission may also occur via tachyzoites contained in blood products, tissue transplants, or unpasteurised milk. However, it is not known which of these routes is more important epidemiologically. In the past, the consumption of raw or undercooked meat, in particular of pigs and sheep, has been regarded as a major route of transmission to humans. However, recent studies showed that the prevalence of T. gondii in meat-producing animals decreased considerably over the past 20 years in areas with intensive farm management. For example, in several countries of the European Union prevalences of T. gondii in fattening pigs are now <1%. Considering these data it is unlikely that pork is still a major source of infection for humans in these countries. However, it is likely that the major routes of transmission are different in human populations with differences in culture and eating habits. In the Americas, recent outbreaks of acute toxoplasmosis in humans have been associated with oocyst contamination of the environment. Therefore, future epidemiological studies on T. gondii infections should consider the role of oocysts as potential sources of infection for humans, and methods to monitor these are currently being developed. This review presents recent epidemiological data on T. gondii, hypotheses on the major routes of transmission to humans in different populations, and preventive measures that may reduce the risk of contracting a primary infection during pregnancy.",,"['Tenter, Astrid M.', 'Heckeroth, Anja R.', 'Weiss, Louis M.']",,,,
,PMC,Cytokine/neurotrophin interaction in the aged central nervous system,http://dx.doi.org/10.1046/j.1469-7580.2000.19740543.x,PMC1468169,,,"Age-associated neurodegenerative diseases such as Alzheimer's disease are characterised by neuronal impairment that leads to cognitive deficits. As certain affected neurons depend on trophic factors such as neurotrophins (NTs), impairment in NT function has been suggested to be a component of neuronal damage associated with such disorders. Age-related neurodegenerative diseases are also characterised by high levels of proinflammatory cytokines such as tumour necrosis factor alpha (TNFα) in the CNS. Because TNFα receptors and certain NT receptors share a high degree of homology and are capable of activating similar signalling pathways, one possibility is that altered cytokine levels may affect NT function in the aged or diseased CNS. Here we wish briefly to review the evidence suggesting a role for cytokine and NT in the onset of age-associated neurodegenerative diseases. We propose that cytokine/NT interactions may alter neuronal homeostasis, thus possibly contributing to some of the neuronal degeneration occurring during such age-associated CNS diseases.",,"['MACDONALD, NANCY J.', 'DECORTI, FRANCESCO', 'PAPPAS, TODD C.', 'TAGLIALATELA, GIULIO']",,,,
,PMC,Coyotes (Canis latrans) as the Reservoir for a Human Pathogenic Bartonella sp.: Molecular Epidemiology of Bartonella vinsonii subsp. berkhoffii Infection in Coyotes from Central Coastal California,,PMC87562,,,"Bartonella vinsonii subsp. berkhoffii was originally isolated from a dog suffering infectious endocarditis and was recently identified as a zoonotic agent causing human endocarditis. Following the coyote bite of a child who developed clinical signs compatible with Bartonella infection in Santa Clara County, Calif., this epidemiological study was conducted. Among 109 coyotes (Canis latrans) from central coastal California, 31 animals (28%) were found to be bacteremic with B. vinsonii subsp. berkhoffii and 83 animals (76%) had B. vinsonii subsp. berkhoffii antibodies. These findings suggest these animals could be the wildlife reservoir of B. vinsonii subsp. berkhoffii. PCR-restriction fragment length polymorphism (PCR-RFLP) analysis of the gltA and 16S rRNA genes for these 31 isolates yielded similar profiles that were identical to those of B. vinsonii subsp. berkhoffii. Partial sequencing of the gltA and 16S rRNA genes, respectively, indicated 99.5 and 100% homology between the coyote isolate and B. vinsonii subsp. berkhoffii (ATCC 51672). PCR-RFLP analysis of the 16S-23S intergenic spacer region showed the existence of two different strain profiles, as has been reported in dogs. Six (19%) of 31 Bartonella bacteremic coyotes exhibited the strain profile that was identified in the type strain of a canine endocarditis case (B. vinsonii subsp. berkhoffii ATCC 51672). The other 25 bacteremic coyotes were infected with a strain that was similar to the strains isolated from healthy dogs. Based on whole bacterial genome analysis by pulsed-field gel electrophoresis (PFGE) with SmaI restriction endonuclease, there was more diversity in fingerprints for the coyote isolates, which had at least 10 major variants compared to the two variants described for domestic dog isolates from the eastern United States. By PFGE analysis, three Bartonella bacteremic coyotes were infected by a strain identical to the one isolated from three healthy dog carriers. Further studies are necessary to elucidate the mode of transmission of B. vinsonii subsp. berkhoffii, especially to identify potential vectors, and to determine how humans become infected.",,"['Chang, Chao-Chin', 'Kasten, Rickie W.', 'Chomel, Bruno B.', 'Simpson, Darren C.', 'Hew, Carrie M.', 'Kordick, Dorsey L.', 'Heller, Remy', 'Piemont, Yves', 'Breitschwerdt, Edward B.']",,,,
,PMC,Characterization of a Borrelia burgdorferi VlsE Invariable Region Useful in Canine Lyme Disease Serodiagnosis by  Enzyme-Linked Immunosorbent Assay,,PMC87557,,,"Sera collected from dogs experimentally infected with Borrelia burgdorferi by tick inoculation were analyzed for an antibody response to each of the six invariable regions (IRs; i.e., IR(1) to IR(6)) of VlsE, the variable surface antigen of B. burgdorferi. Six synthetic peptides (C(1) to C(6)), which reproduced the six IR sequences were used as peptide-based, enzyme-linked immunosorbent assay (ELISA) antigens. Two IRs, IR(2) and IR(6), were found to be immunodominant. Studies with serially collected serum samples from experimentally infected dogs revealed that the antibody response to IR(6) appears earlier and is stronger than that to IR(2). Thus, the IR(6) sequence alone appeared to be sufficient for serodiagnosis. When C(6) alone was used as antigen, the peptide-based ELISA was positive in 7 of 23 dogs (30%) as early as 3 weeks postinfection. All dogs (n = 33) became strongly positive 1 or 2 weeks later, and this response persisted for the entire study, which lasted for 69 weeks. Of 55 sera submitted by veterinarians from dogs suspected of having Lyme disease, 19 were also positive by the C(6) ELISA, compared to 20 positives detected by immunoblot analysis using cultured B. burgdorferi lysates as antigen. The sensitivity of using C(2) and C(6) together for detecting specific antibody in both experimentally infected and clinically diagnosed dogs was not better than sensitivity with C(6) alone, confirming that C(6) suffices as a diagnostic probe. Moreover, the C(6) ELISA yielded 100% specificity with serum samples collected from 70 healthy dogs, 14 dogs with infections other than B. burgdorferi, and 15 animals vaccinated with either outer surface protein A, whole-spirochete vaccines, or the common puppy-vaccines. Therefore, this C(6) ELISA was both sensitive and specific for the serodiagnosis of canine Lyme disease and could be used with vaccinated dogs.",,"['Liang, Fang Ting', 'Jacobson, Richard H.', 'Straubinger, Reinhard K.', 'Grooters, Amy', 'Philipp, Mario T.']",,,,
,PMC,Porcine Reproductive and Respiratory Syndrome Virus: Description of Persistence in Individual Pigs upon Experimental Infection,,PMC110963,,,"We studied the persistence of porcine reproductive and respiratory syndrome virus (PRRSV) in individual experimentally infected pigs, during a period of up to 150 days postinfection (dpi). The results of this study suggest that the persistence of PRRSV involves continuous viral replication but that it is not a true steady-state persistent infection. The virus eventually clears the body and seems to do it in most of the animals by 150 dpi or shortly thereafter. High genetic stability was seen for several regions of the persistent PRRSV's genome, although some consistent mutations in the genes of envelope glycoproteins and M protein were also observed.",,"['Allende, R.', 'Laegreid, W. W.', 'Kutish, G. F.', 'Galeota, J. A.', 'Wills, R. W.', 'Osorio, F. A.']",,,,
,PMC,Expression of the Two Major Envelope Proteins of Equine Arteritis Virus as a Heterodimer Is Necessary for Induction of Neutralizing Antibodies in Mice Immunized with Recombinant Venezuelan Equine Encephalitis Virus Replicon Particles,,PMC110936,,,"RNA replicon particles derived from a vaccine strain of Venezuelan equine encephalitis virus (VEE) were used as a vector for expression of the major envelope proteins (G(L) and M) of equine arteritis virus (EAV), both individually and in heterodimer form (G(L)/M). Open reading frame 5 (ORF5) encodes the G(L) protein, which expresses the known neutralizing determinants of EAV (U. B. R. Balasuriya, J. F. Patton, P. V. Rossitto, P. J. Timoney, W. H. McCollum, and N. J. MacLachlan, Virology 232:114–128, 1997). ORF5 and ORF6 (which encodes the M protein) of EAV were cloned into two different VEE replicon vectors that contained either one or two 26S subgenomic mRNA promoters. These replicon RNAs were packaged into VEE replicon particles by VEE capsid protein and glycoproteins supplied in trans in cells that were coelectroporated with replicon and helper RNAs. The immunogenicity of individual replicon particle preparations (pVR21-G(L), pVR21-M, and pVR100-G(L)/M) in BALB/c mice was determined. All mice developed antibodies against the recombinant proteins with which they were immunized, but only the mice inoculated with replicon particles expressing the G(L)/M heterodimer developed antibodies that neutralize EAV. The data further confirmed that authentic posttranslational modification and conformational maturation of the recombinant G(L) protein occur only in the presence of the M protein and that this interaction is necessary for induction of neutralizing antibodies.",,"['Balasuriya, Udeni B. R.', 'Heidner, Hans W.', 'Hedges, Jodi F.', 'Williams, Jacqueline C.', 'Davis, Nancy L.', 'Johnston, Robert E.', 'MacLachlan, N. James']",,,,
,PMC,Strategy for Systematic Assembly of Large RNA and DNA Genomes: Transmissible Gastroenteritis Virus Model,,PMC110934,,,"A systematic method was developed to assemble functional full-length genomes of large RNA and DNA viruses. Coronaviruses contain the largest single-stranded positive-polarity RNA genome in nature. The ∼30-kb genome, coupled with regions of genomic instability, has hindered the development of a full-length infectious cDNA construct. We have assembled a full-length infectious construct of transmissible gastroenteritis virus (TGEV), an important pathogen in swine. Using a novel approach, six adjoining cDNA subclones that span the entire TGEV genome were isolated. Each clone was engineered with unique flanking interconnecting junctions which determine a precise systematic assembly with only the adjacent cDNA subclones, resulting in an intact TGEV cDNA construct of ∼28.5 kb in length. Transcripts derived from the full-length TGEV construct were infectious, and progeny virions were serially passaged in permissive host cells. Viral antigen production and subgenomic mRNA synthesis were evident during infection and throughout passage. Plaque-purified virus derived from the infectious construct replicated efficiently and displayed similar plaque morphology in permissive host cells. Host range phenotypes of the molecularly cloned and wild-type viruses were similar in cells of swine and feline origin. The recombinant viruses were sequenced across the unique interconnecting junctions, conclusively demonstrating the marker mutations and restriction sites that were engineered into the component clones. Full-length infectious constructs of TGEV will permit the precise genetic modification of the coronavirus genome. The method that we have designed to generate an infectious cDNA construct of TGEV could theoretically be used to precisely reconstruct microbial or eukaryotic genomes approaching several million base pairs in length.",,"['Yount, Boyd', 'Curtis, Kristopher M.', 'Baric, Ralph S.']",,,,
,PMC,The Leader RNA of Coronavirus Mouse Hepatitis Virus Contains an Enhancer-Like Element for Subgenomic mRNA Transcription,,PMC110931,,,"While the 5′ cis-acting sequence of mouse hepatitis virus (MHV) for genomic RNA replication has been determined in several defective interfering (DI) RNA systems, it remains elusive for subgenomic RNA transcription. Previous studies have shown that the leader RNA in the DI genome significantly enhances the efficiency of DI subgenomic mRNA transcription, indicating that the leader RNA is a cis-acting sequence for mRNA transcription. To further characterize the cis-acting sequence, we made a series of deletion mutants, all but one of which have an additional deletion of the cis-acting signal for replication in the 5′ untranslated region. This deletion effectively eliminated the replication of the DI-chloramphenicol acetyltransferase (CAT)-reporter, as demonstrated by the sensitive reverse transcription (RT)-PCR. The ability of these replication-minus mutants to transcribe subgenomic mRNAs was then assessed using the DI RNA-CAT reporter system. Results from both CAT activity and mRNA transcripts detected by RT-PCR showed that a 5′-proximal sequence of 35 nucleotides (nt) at nt 25 to 59 is a cis-acting sequence required for subgenomic RNA transcription, while the consensus repeat sequence of the leader RNA does not have such effect. Analyses of the secondary structure indicate that this 35-nt sequence forms two stem-loops conserved among MHVs. Deletion of this sequence abrogated transcriptional activity and disrupted the predicted stem-loops and overall RNA secondary structure at the 5′ untranslated region, suggesting that the secondary structure formed by this 35-nt sequence may facilitate the downstream consensus sequence accessible for the discontinuous RNA transcription. This may provide a mechanism by which the 5′ cis-acting sequence regulates subgenomic RNA transcription. The 5′-most 24 nt are not essential for transcription, while the 9 nt immediately downstream of the leader enhances RNA transcription. The sequence between nt 86 and 135 had little effect on transcription. This study thus defines the cis-acting transcription signal at the 5′ end of the DI genome.",,"['Wang, Yicheng', 'Zhang, Xuming']",,,,
,PMC,Generation of Subgenomic RNA Directed by a Satellite RNA Associated with Bamboo Mosaic Potexvirus: Analyses of Potexvirus Subgenomic RNA Promoter,,PMC110908,,,"Satellite RNA of bamboo mosaic potexvirus (satBaMV), a single-stranded positive-sense RNA encoding a nonstructural protein of 20 kDa (P20), depends on bamboo mosaic potexvirus (BaMV) for replication and encapsidation. A full-length cDNA clone of satBaMV was used to examine the sequences required for the synthesis of potexvirus subgenomic RNAs (sgRNAs). Subgenomic promoter-like sequences (SGPs), 107 nucleotides (nt) upstream from the capsid protein (CP) gene of BaMV-V, were inserted upstream of the start codon of the P20 gene of satBaMV. Insertion of SGPs gave rise to the synthesis of sgRNA of satBaMV in protoplasts of Nicotiana benthamiana and leaves of Chenopodium quinoa when coinoculated with BaMV-V genomic RNA. Moreover, both the satBaMV cassette and its sgRNA were encapsidated. From analysis of the SGPs by deletion mutation, we concluded that an SGP contains one core promoterlike sequence (nt −30 through +16), two upstream enhancers (nt −59 through −31 and −91 through −60), and one downstream enhancer (nt +17 through +52), when the transcription initiation site is taken as +1. Site-directed mutagenesis and compensatory mutation to disrupt and restore potential base pairing in the core promoter-like sequence suggest that the stem-loop structure is important for the function of SGP in vivo. Likewise, the insertion of a putative SGP of the BaMV open reading frame 2 gene or a heterologous SGP of potato virus X resulted in generation of an sgRNA. The satBaMV cassette should be a useful tool to gain insight into sequences required for the synthesis of potexvirus sgRNAs.",,"['Lee, Yun-Shien', 'Hsu, Yau-Heiu', 'Lin, Na-Sheng']",,,,
,PMC,Functional Importance of the Coiled-Coil of the Ebola Virus Glycoprotein,,PMC102058,,,"Ebola virus contains a single glycoprotein (GP) that is responsible for receptor binding and membrane fusion and is proteolytically cleaved into disulfide-linked GP1 and GP2 subunits. The GP2 subunit possesses a coiled-coil motif, which plays an important role in the oligomerization and fusion activity of other viral GPs. To determine the functional significance of the coiled-coil motif of GP2, we examined the effects of peptides corresponding to the coiled-coil motif of GP2 on the infectivity of a mutant vesicular stomatitis virus (lacking the receptor-binding/fusion protein) pseudotyped with the Ebola virus GP. A peptide corresponding to the C-terminal helix reduced the infectivity of the pseudotyped virus. We next introduced alanine substitutions into hydrophobic residues in the coiled-coil motif to identify residues important for GP function. None of the substitutions affected GP oligomerization, but some mutations, two in the N-terminal helix and all in the C-terminal helix, reduced the ability of GP to confer infectivity to the mutant vesicular stomatitis virus without affecting the transport of GP to the cell surface, its incorporation into virions, and the production of virus particles. These results indicate that the coiled-coil motif of GP2 plays an important role in facilitating the entry of Ebola virus into host cells and that peptides corresponding to this region could act as efficient antiviral agents.",,"['Watanabe, Shinji', 'Takada, Ayato', 'Watanabe, Tokiko', 'Ito, Hiroshi', 'Kida, Hiroshi', 'Kawaoka, Yoshihiro']",,,,
,PMC,Soluble isoforms of CEACAM1 containing the A2 domain: increased serum levels in patients with obstructive jaundice and differences in 3-fucosyl-N-acetyl-lactosamine moiety,http://dx.doi.org/10.1046/j.1365-2567.2000.00113.x,PMC2327077,,,"CEACAM1 (biliary glycoprotein or CD66a) is a member of the carcinoembryonic antigen (CEA) subgroup of the CEA family. Eleven RNA isoforms derived from the splicing of a single CEACAM1 gene have been described. Some of the CEACAM1 isoforms have been recognized by the CD66 antibodies in T and B lymphocytes, natural killer cells, granulocytes and epithelial cells in several human tissues. Although it is also present in soluble form in bile and serum, and elevated levels have been found in the serum of patients with liver diseases, it is not known which isoforms are primarily involved. In order to learn more about the distribution and properties of particular CEACAM1 isoforms, we have prepared a monoclonal antibody specific for the A2 domain of CEACAM1, designated TEC-11. This antibody does not cross-react with other members of the CEA family. Immunoblotting analysis revealed that the TEC-11 epitope was present in all cell types expressing CEACAM1 containing the A2 domain [CEACAM1(A2)], including granulocytes (160 000 MW isoform) and sperm cells (140 000 MW isoform). A 115 000 MW isoform of CEACAM1(A2) was present in human serum, bile, saliva and seminal fluid. Human bile, saliva and seminal fluid also contained the 160 000 MW CEACAM1(A2) isoform. Significantly higher serum levels of the 115 000 MW CEACAM1(A2) isoform were detected in patients with obstructive jaundice. The 160 000 MW isoform of CEACAM1(A2) in bile, but not a 115 000 MW isoform in serum and bile, carried the 3-fucosyl-N-acetyl-lactosamine moiety. The combined data indicate that various isoforms of CEACAM1(A2) are present in different body fluids where they could take part in different CEACAM1-mediated functions.",,"['Dráberová, L', 'Černá, H', 'Brodská, H', 'Boubelík, M', 'Watt, S M', 'Stanners, C P', 'Dráber, P']",,,,
,PMC,Alphavirus RNA Genome Repair and Evolution: Molecular Characterization of Infectious Sindbis Virus Isolates Lacking a  Known Conserved Motif at the 3′ End of the Genome,,PMC112414,,,"The 3′ nontranslated region of the genomes of Sindbis virus (SIN) and other alphaviruses carries several repeat sequence elements (RSEs) as well as a 19-nucleotide (nt) conserved sequence element (3′CSE). The 3′CSE and the adjoining poly(A) tail of the SIN genome are thought to act as viral promoters for negative-sense RNA synthesis and genome replication. Eight different SIN isolates that carry altered 3′CSEs were studied in detail to evaluate the role of the 3′CSE in genome replication. The salient findings of this study as it applies to SIN infection of BHK cells are as follows: i) the classical 19-nt 3′CSE of the SIN genome is not essential for genome replication, long-term stability, or packaging; ii) compensatory amino acid or nucleotide changes within the SIN genomes are not required to counteract base changes in the 3′ terminal motifs of the SIN genome; iii) the 5′ 1-kb regions of all SIN genomes, regardless of the differences in 3′ terminal motifs, do not undergo any base changes even after 18 passages; iv) although extensive addition of AU-rich motifs occurs in the SIN genomes carrying defective 3′CSE, these are not essential for genome viability or function; and v) the newly added AU-rich motifs are composed predominantly of RSEs. These findings are consistent with the idea that the 3′ terminal AU-rich motifs of the SIN genomes do not bind directly to the viral polymerase and that cellular proteins with broad AU-rich binding specificity may mediate this interaction. In addition to the classical 3′CSE, other RNA motifs located elsewhere in the SIN genome must play a major role in template selection by the SIN RNA polymerase.",,"['George, Jyothi', 'Raju, Ramaswamy']",,,,
,PMC,Biochemical Characterization of the Equine Arteritis Virus Helicase Suggests a Close Functional Relationship between  Arterivirus and Coronavirus Helicases,,PMC112390,,,"The arterivirus equine arteritis virus nonstructural protein 10 (nsp10) has previously been predicted to contain a Zn finger structure linked to a superfamily 1 (SF1) helicase domain. A recombinant form of nsp10, MBP-nsp10, was produced in Escherichia coli as a fusion protein with the maltose-binding protein. The protein was partially purified by affinity chromatography and shown to have ATPase activity that was strongly stimulated by poly(dT), poly(U), and poly(dA) but not by poly(G). The protein also had both RNA and DNA duplex-unwinding activities that required the presence of 5′ single-stranded regions on the partial-duplex substrates, indicating a 5′-to-3′ polarity in the unwinding reaction. Results of this study suggest a close functional relationship between the arterivirus nsp10 and the coronavirus helicase, for which NTPase and duplex-unwinding activities were recently demonstrated. In a number of biochemical properties, both arterivirus and coronavirus SF1 helicases differ significantly from the previously characterized RNA virus SF1 and SF2 enzymes. Thus, the combined data strongly support the idea that nidovirus helicases may represent a separate group of RNA virus-encoded helicases with distinct properties.",,"['Seybert, Anja', 'van Dinten, Leonie C.', 'Snijder, Eric J.', 'Ziebuhr, John']",,,,
,PMC,Passage of Classical Swine Fever Virus in Cultured Swine Kidney Cells Selects Virus Variants That Bind to Heparan Sulfate due to  a Single Amino Acid Change in Envelope Protein E(rns),,PMC112386,,,"Infection of cells with Classical swine fever virus (CSFV) is mediated by the interaction of envelope glycoprotein E(rns) and E2 with the cell surface. In this report we studied the role of the cell surface glycoaminoglycans (GAGs), chondroitin sulfates A, B, and C (CS-A, -B, and -C), and heparan sulfate (HS) in the initial binding of CSFV strain Brescia to cells. Removal of HS from the surface of swine kidney cells (SK6) by heparinase I treatment almost completely abolished infection of these cells with virus that was extensively passaged in swine kidney cells before it was cloned (clone C1.1.1). Infection with C1.1.1 was inhibited completely by heparin (a GAG chemically related to HS but sulfated to a higher extent) and by dextran sulfate (an artificial highly sulfated polysaccharide), whereas HS and CS-A, -B, and -C were unable to inhibit infection. Bound C1.1.1 virus particles were released from the cell surface by treatment with heparin. Furthermore, C1.1.1 virus particles and CSFV E(rns) purified from insect cells bound to immobilized heparin, whereas purified CSFV E2 did not. These results indicate that initial binding of this virus clone is accomplished by the interaction of E(rns) with cell surface HS. In contrast, infection of SK6 cells with virus clones isolated from the blood of an infected pig and minimally passaged in SK6 cells was not affected by heparinase I treatment of cells and the addition of heparin to the medium. However, after one additional round of amplification in SK6 cells, infection with these virus clones was affected by heparinase I treatment and heparin. Sequence analysis of the E(rns) genes of these virus clones before and after amplification in SK6 cells showed that passage in SK6 cells resulted in a change of an Ser residue to an Arg residue in the C terminus of E(rns) (amino acid 476 in the polyprotein of CSFV). Replacement of the E(rns) gene of an infectious DNA copy of C1.1.1 with the E(rns) genes of these virus variants proved that acquisition of this Arg was sufficient to alter an HS-independent virus to a virus that uses HS as an E(rns) receptor.",,"['Hulst, M. M.', 'van Gennip, H. G. P.', 'Moormann, R. J. M.']",,,,
,PMC,E2-p7 Region of the Bovine Viral Diarrhea Virus Polyprotein: Processing and Functional Studies,,PMC112379,,,"The genes encoding pestivirus E2 and NS2-3 are separated by a sequence that encodes a small hydrophobic polypeptide with an apparent molecular mass of 6 to 7 kDa (p7). It has been shown that cleavage between E2 and p7 is incomplete, resulting in proteins E2-p7, E2, and p7. We found no precursor-product relationship between E2-p7 and E2, which indicates a stable nature of E2-p7. To study the function of the E2-p7 region of the polyprotein, mutations were introduced into an infectious cDNA of bovine viral diarrhea virus (BVDV). When cleavage between E2 and p7 was abolished, viral RNA replication occurred; however, no infectious virus could be recovered. A corresponding result was obtained with a construct encompassing a large in-frame deletion of p7. To prevent synthesis of E2-p7, a translational stop codon was introduced after the last codon of the E2 gene and an internal ribosome entry site element followed by a signal peptide coding sequence was inserted upstream of the p7 gene. Transfection of RNA transcribed from the bicistronic construct led to the release of infectious virus particles. Thus, synthesis of E2-p7 is not essential for the generation of infectious virions. Cell lines constitutively expressing BVDV p7 and/or E2 were generated for complementation studies. Transfection of BVDV RNAs with point mutations or a deletion in the E2-p7 region into the complementing cell lines led to the generation of infectious virions. According to our studies, p7 as well as E2 can be complemented in trans.",,"['Harada, Takashi', 'Tautz, Norbert', 'Thiel, Heinz-Jürgen']",,,,
,PMC,Human Coronavirus 229E Infects Polarized Airway Epithelia from the Apical Surface,,PMC102122,,,"Gene transfer to differentiated airway epithelia with existing viral vectors is very inefficient when they are applied to the apical surface. This largely reflects the polarized distribution of receptors on the basolateral surface. To identify new receptor-ligand interactions that might be used to redirect vectors to the apical surface, we investigated the process of infection of airway epithelial cells by human coronavirus 229E (HCoV-229E), a common cause of respiratory tract infections. Using immunohistochemistry, we found the receptor for HCoV-229E (CD13 or aminopeptidase N) localized mainly to the apical surface of airway epithelia. When HCoV-229E was applied to the apical or basolateral surface of well-differentiated primary cultures of human airway epithelia, infection primarily occurred from the apical side. Similar results were noted when the virus was applied to cultured human tracheal explants. Newly synthesized virions were released mainly to the apical side. Thus, HCoV-229E preferentially infects human airway epithelia from the apical surface. The spike glycoprotein that mediates HCoV-229E binding and fusion to CD13 is a candidate for pseudotyping retroviral envelopes or modifying other viral vectors.",,"['Wang, Guoshun', 'Deering, Camille', 'Macke, Michael', 'Shao, Jianqiang', 'Burns, Royce', 'Blau, Dianna M.', 'Holmes, Kathryn V.', 'Davidson, Beverly L.', 'Perlman, Stanley', 'McCray, Paul B.']",,,,
,PMC,Demyelination Determinants Map to the Spike Glycoprotein Gene of Coronavirus Mouse Hepatitis Virus,,PMC102119,,,"Demyelination is the pathologic hallmark of the human immune-mediated neurologic disease multiple sclerosis, which may be triggered or exacerbated by viral infections. Several experimental animal models have been developed to study the mechanism of virus-induced demyelination, including coronavirus mouse hepatitis virus (MHV) infection in mice. The envelope spike (S) glycoprotein of MHV contains determinants of properties essential for virus-host interactions. However, the molecular determinants of MHV-induced demyelination are still unknown. To investigate the mechanism of MHV-induced demyelination, we examined whether the S gene of MHV contains determinants of demyelination and whether demyelination is linked to viral persistence. Using targeted RNA recombination, we replaced the S gene of a demyelinating virus (MHV-A59) with the S gene of a closely related, nondemyelinating virus (MHV-2). Recombinant viruses containing an S gene derived from MHV-2 in an MHV-A59 background (Penn98-1 and Penn98-2) exhibited a persistence-positive, demyelination-negative phenotype. Thus, determinants of demyelination map to the S gene of MHV. Furthermore, viral persistence is insufficient to induce demyelination, although it may be a prerequisite for the development of demyelination.",,"['Das Sarma, Jayasri', 'Fu, Li', 'Tsai, Jean C.', 'Weiss, Susan R.', 'Lavi, Ehud']",,,,
,PMC,Efficient Homologous RNA Recombination and Requirement for an Open Reading Frame during Replication of Equine Arteritis Virus Defective Interfering RNAs,,PMC102103,,,"Equine arteritis virus (EAV), the prototype arterivirus, is an enveloped plus-strand RNA virus with a genome of approximately 13 kb. Based on similarities in genome organization and protein expression, the arteriviruses have recently been grouped together with the coronaviruses and toroviruses in the newly established order Nidovirales. Previously, we reported the construction of pEDI, a full-length cDNA copy of EAV DI-b, a natural defective interfering (DI) RNA of 5.6 kb (R. Molenkamp et al., J. Virol. 74:3156–3165, 2000). EDI RNA consists of three noncontiguous parts of the EAV genome fused in frame with respect to the replicase gene. As a result, EDI RNA contains a truncated replicase open reading frame (EDI-ORF) and encodes a truncated replicase polyprotein. Since some coronavirus DI RNAs require the presence of an ORF for their efficient propagation, we have analyzed the importance of the EDI-ORF in EDI RNA replication. The EDI-ORF was disrupted at different positions by the introduction of frameshift mutations. These were found either to block DI RNA replication completely or to be removed within one virus passage, probably due to homologous recombination with the helper virus genome. Using recombination assays based on EDI RNA and full-length EAV genomes containing specific mutations, the rates of homologous RNA recombination in the 3′- and 5′-proximal regions of the EAV genome were studied. Remarkably, the recombination frequency in the 5′-proximal region was found to be approximately 100-fold lower than that in the 3′-proximal part of the genome.",,"['Molenkamp, Richard', 'Greve, Sophie', 'Spaan, Willy J. M.', 'Snijder, Eric J.']",,,,
,PMC,Neuroinvasion by Human Respiratory Coronaviruses,,PMC102086,,,"Human coronaviruses (HCoV) cause common colds but can also infect neural cell cultures. To provide definitive experimental evidence for the neurotropism and neuroinvasion of HCoV and its possible association with multiple sclerosis (MS), we have performed an extensive search and characterization of HCoV RNA in a large panel of human brain autopsy samples. Very stringent reverse transcription-PCR with two primer pairs for both viral strains (229E and OC43), combined with Southern hybridization, was performed on samples from 90 coded donors with various neurological diseases (39 with MS and 26 with other neurological diseases) or normal controls (25 patients). We report that 44% (40 of 90) of donors were positive for 229E and that 23% (21 of 90) were positive for OC43. A statistically significant higher prevalence of OC43 in MS patients (35.9%; 14 of 39) than in controls (13.7%; 7 of 51) was observed. Sequencing of nucleocapsid protein (N) gene amplicons revealed point mutations in OC43, some consistently found in three MS patient brains and one normal control but never observed in laboratory viruses. In situ hybridization confirmed the presence of viral RNA in brain parenchyma, outside blood vessels. The presence of HCoV in human brains is consistent with neuroinvasion by these respiratory pathogens. Further studies are needed to distinguish between opportunistic and disease-associated viral presence in human brains.",,"['Arbour, Nathalie', 'Day, Robert', 'Newcombe, Jia', 'Talbot, Pierre J.']",,,,
,PMC,Intranasal Administration of 2/6-Rotavirus-Like Particles with Mutant Escherichia coli Heat-Labile Toxin (LT-R192G) Induces  Antibody-Secreting Cell Responses but Not Protective  Immunity in Gnotobiotic Pigs,,PMC102078,,,"We investigated the immunogenicity of recombinant double-layered rotavirus-like particle (2/6-VLPs) vaccines derived from simian SA11 or human (VP6) Wa and bovine RF (VP2) rotavirus strains. The 2/6-VLPs were administered to gnotobiotic pigs intranasally (i.n.) with a mutant Escherichia coli heat-labile toxin, LT-R192G (mLT), as mucosal adjuvant. Pigs were challenged with virulent Wa (P1A[8],G1) human rotavirus at postinoculation day (PID) 21 (two-dose VLP regimen) or 28 (three-dose VLP regimen). In vivo antigen-activated antibody-secreting cells (ASC) (effector B cells) and in vitro antigen-reactivated ASC (derived from memory B cells) from intestinal and systemic lymphoid tissues (duodenum, ileum, mesenteric lymph nodes [MLN], spleen, peripheral blood lymphocytes [PBL], and bone marrow lymphocytes) collected at selected times were quantitated by enzyme-linked immunospot assays. Rotavirus-specific immunoglobulin M (IgM), IgA, and IgG ASC and memory B-cell responses were detected by PID 21 or 28 in intestinal and systemic lymphoid tissues after i.n. inoculation with two or three doses of 2/6-VLPs with or without mLT. Greater mean numbers of virus-specific ASC and memory B cells in all tissues prechallenge were induced in pigs inoculated with two doses of SA11 2/6-VLPs plus mLT compared to SA11 2/6-VLPs without mLT. After challenge, anamnestic IgA and IgG ASC and memory B-cell responses were detected in intestinal lymphoid tissues of all VLP-inoculated groups, but serum virus-neutralizing antibody titers were not significantly enhanced compared to the challenged controls. Pigs inoculated with Wa-RF 2/6-VLPs (with or without mLT) developed higher anamnestic IgA and IgG ASC responses in ileum after challenge compared to pigs inoculated with SA11 2/6-VLPs (with or without mLT). Three doses of SA 11 2/6-VLP plus mLT induced the highest mean numbers of IgG memory B cells in MLN, spleen, and PBL among all groups postchallenge. However, no significant protection against diarrhea or virus shedding was evident in any of the 2/6-VLP (with or without mLT)-inoculated pigs after challenge with virulent Wa human rotavirus. These results indicate that 2/6-VLP vaccines are immunogenic in gnotobiotic pigs when inoculated i.n. and that the adjuvant mLT enhanced their immunogenicity. However, i.n. inoculation of gnotobiotic pigs with 2/6-VLPs did not confer protection against human rotavirus challenge.",,"['Yuan, Lijuan', 'Geyer, Annelise', 'Hodgins, Douglas C.', 'Fan, Zhiqian', 'Qian, Yuan', 'Chang, Kyeong-Ok', 'Crawford, Sue E.', 'Parreño, Viviana', 'Ward, Lucy A.', 'Estes, Mary K.', 'Conner, Margaret E.', 'Saif, Linda J.']",,,,
,PMC,"Helicase and Capping Enzyme Active Site Mutations in Brome Mosaic Virus Protein 1a Cause Defects in Template Recruitment,  Negative-Strand RNA Synthesis, and  Viral RNA Capping",,PMC102074,,,"Brome mosaic virus (BMV) encodes two RNA replication proteins: 1a, which contains RNA capping and helicase-like domains, and 2a, which is related to polymerases. BMV 1a and 2a can direct virus-specific RNA replication in the yeast Saccharomyces cerevisiae, which reproduces the known features of BMV replication in plant cells. We constructed single amino acid point mutations at the predicted capping and helicase active sites of 1a and analyzed their effects on BMV RNA3 replication in yeast. The helicase mutants showed no function in any assays used: they were strongly defective in template recruitment for RNA replication, as measured by 1a-induced stabilization of RNA3, and they synthesized no detectable negative-strand or subgenomic RNA. Capping domain mutants divided into two groups. The first exhibited increased template recruitment but nevertheless allowed only low levels of negative-strand and subgenomic mRNA synthesis. The second was strongly defective in template recruitment, made very low levels of negative strands, and made no detectable subgenomes. To distinguish between RNA synthesis and capping defects, we deleted chromosomal gene XRN1, encoding the major exonuclease that degrades uncapped mRNAs. XRN1 deletion suppressed the second but not the first group of capping mutants, allowing synthesis and accumulation of large amounts of uncapped subgenomic mRNAs, thus providing direct evidence for the importance of the viral RNA capping function. The helicase and capping enzyme mutants showed no complementation. Instead, at high levels of expression, a helicase mutant dominantly interfered with the function of the wild-type protein. These results are discussed in relation to the interconnected functions required for different steps of positive-strand RNA virus replication.",,"['Ahola, Tero', 'den Boon, Johan A.', 'Ahlquist, Paul']",,,,
,PMC,RNase L-Independent Specific 28S rRNA Cleavage in Murine Coronavirus-Infected Cells,,PMC102073,,,"We characterized a novel 28S rRNA cleavage in cells infected with the murine coronavirus mouse hepatitis virus (MHV). The 28S rRNA cleavage occurred as early as 4 h postinfection (p.i.) in MHV-infected DBT cells, with the appearance of subsequent cleavage products and a decrease in the amount of intact 28S rRNA with increasing times of infection; almost all of the intact 28S rRNA disappeared by 24 h p.i. In contrast, no specific 18S rRNA cleavage was detected in infected cells. MHV-induced 28S rRNA cleavage was detected in all MHV-susceptible cell lines and all MHV strains tested. MHV replication was required for the 28S rRNA cleavage, and mature cytoplasmic 28S rRNA underwent cleavage. In certain combination of cells and viruses, pretreatment of virus-infected cells with interferon activates a cellular endoribonuclease, RNase L, that causes rRNA degradation. No interferon was detected in the inoculum used for MHV infection. Addition of anti-interferon antibody to MHV-infected cells did not inhibit 28S rRNA cleavage. Furthermore, 28S rRNA cleavage occurred in an MHV-infected mouse embryonic fibroblast cell line derived from RNase L knockout mice. Thus, MHV-induced 28S rRNA cleavage was independent of the activation of RNase L. MHV-induced 28S rRNA cleavage was also different from apoptosis-related rRNA degradation, which usually occurs concomitantly with DNA fragmentation. In MHV-infected 17Cl-1 cells, 28S rRNA cleavage preceded DNA fragmentation by at least 18 h. Blockage of apoptosis in MHV-infected 17Cl-1 cells by treatment with a caspase inhibitor did not block 28S rRNA cleavage. Furthermore, MHV-induced 28S rRNA cleavage occurred in MHV-infected DBT cells that do not show apoptotic signs, including activation of caspase-3 and DNA fragmentation. Thus, MHV-induced 28S rRNA cleavage appeared to differ from any rRNA degradation mechanism described previously.",,"['Banerjee, Sangeeta', 'An, Sungwhan', 'Zhou, Aimin', 'Silverman, Robert H.', 'Makino, Shinji']",,,,
,PMC,Heterogeneous nuclear ribonucleoprotein A1 regulates RNA synthesis of a cytoplasmic virus,http://dx.doi.org/10.1093/emboj/19.17.4701,PMC302072,,,"Heterogeneous nuclear ribonucleoprotein (hnRNP A1) is involved in pre-mRNA splicing in the nucleus and translational regulation in the cytoplasm. In the present study, we demonstrate that hnRNP A1 also participates in the transcription and replication of a cytoplasmic RNA virus, mouse hepatitis virus (MHV). Overexpression of hnRNP A1 accelerated the kinetics of viral RNA synthesis, whereas the expression in the cytoplasm of a dominant-negative hnRNP A1 mutant that lacks the nuclear transport domain significantly delayed it. The hnRNP A1 mutant caused a global inhibition of viral mRNA transcription and genomic replication, and also a preferential inhibition of the replication of defective-interfering RNAs. Similar to the wild-type hnRNP A1, the hnRNP A1 mutant complexed with an MHV polymerase gene product, the nucleocapsid protein and the viral RNA. However, in contrast to the wild-type hnRNP A1, the mutant protein failed to bind a 250 kDa cellular protein, suggesting that the recruitment of cellular proteins by hnRNP A1 is important for MHV RNA synthesis. Our findings establish the importance of cellular factors in viral RNA-dependent RNA synthesis.",,"['Shi, Stephanie T.', 'Huang, Peiyong', 'Li, Hsin-Pai', 'Lai, Michael M.C.']",,,,
,PMC,Coronavirus and Pasteurella Infections in Bovine Shipping Fever Pneumonia and Evans' Criteria for Causation,,PMC87376,,,"Respiratory tract infections with viruses and Pasteurella spp. were determined sequentially among 26 cattle that died during two severe epizootics of shipping fever pneumonia. Nasal swab and serum samples were collected prior to onset of the epizootics, during disease progression, and after death, when necropsies were performed and lung samples were collected. Eighteen normal control cattle also were sampled at the beginning of the epizootics as well as at weekly intervals for 4 weeks. Respiratory bovine coronaviruses (RBCV) were isolated from nasal secretions of 21 and 25 cattle before and after transport. Two and 17 cattle nasally shed Pasteurella spp. before and after transport, respectively. RBCV were isolated at titers of 1 × 10(3) to 1.2 × 10(7) PFU per g of lung tissue from 18 cattle that died within 7 days of the epizootics, but not from the lungs of the remaining cattle that died on days 9 to 36. Twenty-five of the 26 lung samples were positive for Pasteurella spp., and their CFU ranged between 4.0 × 10(5) and 2.3 × 10(9) per g. Acute and subacute exudative, necrotizing lobar pneumonia characterized the lung lesions of these cattle with a majority of pneumonic lung lobes exhibiting fibronecrotic and exudative changes typical of pneumonic pasteurellosis, but other lung lobules had histological changes consisting of bronchiolitis and alveolitis typical of virus-induced changes. These cattle were immunologically naive to both infectious agents at the onset of the epizootics, but those that died after day 7 had rising antibody titers against RBCV and Pasteurella haemolytica. In contrast, the 18 clinically normal and RBCV isolation-negative cattle had high hemagglutinin inhibition antibody titers to RBCV from the beginning, while their antibody responses to P. haemolytica antigens were delayed. Evans' criteria for causation were applied to our findings because of the multifactorial nature of shipping fever pneumonia. This analysis identified RBCV as the primary inciting cause in these two epizootics. These viruses were previously not recognized as a causative agent in this complex respiratory tract disease of cattle.",,"['Storz, Johannes', 'Lin, Xiaoqing', 'Purdy, Charles W.', 'Chouljenko, Vladimir N.', 'Kousoulas, Konstantin G.', 'Enright, Frederick M.', 'Gilmore, William C.', 'Briggs, Robert E.', 'Loan, Raymond W.']",,,,
,PMC,Avian Nephritis Virus (ANV) as a New Member of the Family Astroviridae and Construction of Infectious ANV cDNA,,PMC116360,,,"The complete RNA genome of the avian nephritis virus (ANV) associated with acute nephritis in chickens has been molecularly cloned and sequenced. Excluding the poly(A) tail, the genome comprises 6,927 nucleotides and contains three sequential open reading frames (ORFs). The first ORF (ORF 1a) contains a sequence encoding a serine protease motif, and the second ORF (ORF 1b) has a sequence encoding an RNA-dependent RNA polymerase. ORF 1a may be linked to the second ORF by a ribosomal frameshifting mechanism. The third ORF (ORF 2) may encode the virion structural proteins as a polyprotein precursor. Two RNAs, probably genonic and subgenonic RNA (7.5 and 3.0 kb), were detected in the cytoplasm of ANV-infected cells. ANV and human astroviruses have the same genonic organization, and both are characterized by the presence of two RNA bands. The amino acid homologies of the products of ORF 1a, 1b, and 2 were 20.3, 41.9, and 25.8% to products of the corresponding ORFs of human astrovirus serotype 1 (A/88 Newcastle strain). We have constructed a genonic-length cDNA clone of ANV to test whether the in vitro transcript is infectious. When a chicken kidney cell culture was transfected with RNA transcribed in vitro and the cDNA clone, infectious virus was produced with cytopathic effects in the absence of trypsin. These observations suggested that the ANV (G-4260 strain) is a new genus of the family Astroviridae.",,"['Imada, Tadao', 'Yamaguchi, Shigeo', 'Mase, Masaji', 'Tsukamoto, Kenji', 'Kubo, Masanori', 'Morooka, Akira']",,,,
,PMC,Characterization of the Coronavirus M Protein and Nucleocapsid Interaction in Infected Cells,,PMC112346,,,"Coronavirus contains three envelope proteins, M, E and S, and a nucleocapsid, which consists of genomic RNA and N protein, within the viral envelope. We studied the macromolecular interactions involved in coronavirus assembly in cells infected with a murine coronavirus, mouse hepatitis virus (MHV). Coimmunoprecipitation analyses demonstrated an interaction between N protein and M protein in infected cells. Pulse-labeling experiments showed that newly synthesized, unglycosylated M protein interacted with N protein in a pre-Golgi compartment, which is part of the MHV budding site. Coimmunoprecipitation analyses further revealed that M protein interacted with only genomic-length MHV mRNA, mRNA 1, while N protein interacted with all MHV mRNAs. These data indicated that M protein interacted with the nucleocapsid, consisting of N protein and mRNA 1, in infected cells. The M protein-nucleocapsid interaction occurred in the absence of S and E proteins. Intracellular M protein-N protein interaction was maintained after removal of viral RNAs by RNase treatment. However, the M protein-N protein interaction did not occur in cells coexpressing M protein and N protein alone. These data indicated that while the M protein-N protein interaction, which is independent of viral RNA, occurred in the M protein-nucleocapsid complex, some MHV function(s) was necessary for the initiation of M protein-nucleocapsid interaction. The M protein-nucleocapsid interaction, which occurred near or at the MHV budding site, most probably represented the process of specific packaging of the MHV genome into MHV particles.",,"['Narayanan, Krishna', 'Maeda, Akihiko', 'Maeda, Junko', 'Makino, Shinji']",,,,
,PMC,Identification of Mouse Hepatitis Virus Papain-Like  Proteinase 2 Activity,,PMC112322,,,"Mouse hepatitis virus (MHV) is a 31-kb positive-strand RNA virus that is replicated in the cytoplasm of infected cells by a viral RNA-dependent RNA polymerase, termed the replicase. The replicase is encoded in the 5′-most 22 kb of the genomic RNA, which is translated to produce a polyprotein of >800 kDa. The replicase polyprotein is extensively processed by viral and perhaps cellular proteinases to give rise to a functional replicase complex. To date, two of the MHV replicase-encoded proteinases, papain-like proteinase 1 (PLP1) and the poliovirus 3C-like proteinase (3CLpro), have been shown to process the replicase polyprotein. In this report, we describe the cloning, expression, and activity of the third MHV proteinase domain, PLP2. We show that PLP2 cleaves a substrate encoding the first predicted membrane-spanning domain (MP1) of the replicase polyprotein. Cleavage of MP1 and release of a 150-kDa intermediate, p150, are likely to be important for embedding the replicase complex in cellular membranes. Using an antiserum (anti-D11) directed against the C terminus of the MP1 domain, we verified that p150 encompasses the MP1 domain and identified a 44-kDa protein (p44) as a processed product of p150. Pulse-chase experiments showed that p150 is rapidly generated in MHV-infected cells and that p44 is processed from the p150 precursor. Protease inhibitor studies revealed that unlike 3CLpro activity, PLP2 activity is not sensitive to cysteine protease inhibitor E64d. Furthermore, coexpression studies using the PLP2 domain and a substrate encoding the MP1 cleavage site showed that PLP2 acts efficiently in trans. Site-directed mutagenesis studies confirmed the identification of cysteine 1715 as a catalytic residue of PLP2. This study is the first to report enzymatic activity of the PLP2 domain and to demonstrate that three distinct viral proteinase activities process the MHV replicase polyprotein.",,"['Kanjanahaluethai, Amornrat', 'Baker, Susan C.']",,,,
,PMC,Role of Viral Persistence in Retaining CD8(+) T Cells within the Central Nervous System,,PMC112321,,,"The continued presence of virus-specific CD8(+) T cells within the central nervous system (CNS) following resolution of acute viral encephalomyelitis implicates organ-specific retention. The role of viral persistence in locally maintaining T cells was investigated by infecting mice with either a demyelinating, paralytic (V-1) or nonpathogenic (V-2) variant of a neurotropic mouse hepatitis virus, which differ in the ability to persist within the CNS. Class I tetramer technology revealed more infiltrating virus-specific CD8(+) T cells during acute V-1 compared to V-2 infection. However, both total and virus-specific CD8(+) T cells accumulated at similar peak levels in spinal cords by day 10 postinfection (p.i.). Decreasing viral RNA levels in both brains and spinal cords following initial virus clearance coincided with an overall progressive loss of both total and virus-specific CD8(+) T cells. By 9 weeks p.i., T cells had largely disappeared from brains of both infected groups, consistent with the decline of viral RNA. T cells also completely disappeared from V-2-infected spinal cords coincident with the absence of viral RNA. By contrast, a significant number of CD8(+) T cells which contained detectable viral RNA were recovered from spinal cords of V-1-infected mice. The data indicate that residual virus from a primary CNS infection is a vital component in mediating local retention of both CD8(+) and CD4(+) T cells and that once minimal thresholds of stimuli are lost, T cells within the CNS cannot survive in an autonomous fashion.",,"['Marten, Norman W.', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.']",,,,
,PMC,"Antizyme expression: a subversion of triplet decoding, which is remarkably conserved by evolution, is a sensor for an autoregulatory circuit",,PMC110703,,,The efficiency of programmed ribosomal frameshifting in decoding antizyme mRNA is the sensor for an autoregulatory circuit that controls cellular polyamine levels in organisms ranging from the yeast Schizosaccharomyces pombe to Drosophila to mammals. Comparison of the frameshift sites and flanking stimulatory signals in many organisms now permits a reconstruction of the likely evolutionary path of the remarkably conserved mRNA sequences involved in the frameshifting.,,"['Ivanov, Ivaylo P.', 'Gesteland, Raymond F.', 'Atkins, John F.']",,,,
,PMC,Quantitative analysis of the CD8+ T-cell response to readily eliminated and persistent viruses.,,PMC1692813,,,"The recent development of techniques for the direct staining of peptide-specific CD8+ T cells has revolutionized the analysis of cell-mediated immunity (CMI) in virus infections. This approach has been used to quantify the acute and long-term consequences of infecting laboratory mice with the readily eliminated influenza A viruses (fluA) and a persistent gammaherpesvirus (gammaHV). It is now, for the first time, possible to work with real numbers in the analysis of CD8+ T CMI, and to define various characteristics of the responding lymphocytes both by direct flow cytometric analysis and by sorting for further in vitro manipulation. Relatively little has yet been done from the latter aspect, though we are rapidly accumulating a mass of numerical data. The acute, antigen-driven phases of the fluA and gammaHV-specific response look rather similar, but CD8+ T-cell numbers are maintained in the long term at a higher 'set point' in the persistent infection. Similarly, these 'memory' T cells continue to divide at a much greater rate in the gammaHV-infected mice. New insights have also been generated on the nature of the recall response following secondary challenge in both experimental systems, and the extent of protection conferred by large numbers of virus-specific CD8+ T cells has been determined. However, there are still many parameters that have received little attention, partly because they are difficult to measure. These include the rate of antigen-specific CD8+ T-cell loss, the extent of the lymphocyte 'diaspora' to other tissues, and the diversity of functional characteristics, turnover rates, clonal life spans and recirculation profiles. The basic question for immunologists remains how we reconcile the extraordinary plasticity of the immune system with the mechanisms that maintain a stable milieu interieur. This new capacity to quantify CD8+ T-cell responses in readily manipulated mouse models has obvious potential for illuminating homeostatic control, particularly if the experimental approaches to the problem are designed in the context of appropriate predictive models.",,"['Doherty, P C', 'Riberdy, J M', 'Belz, G T']",,,,
,PMC,Molecular ophthalmology: an update on animal models for retinal degenerations and dystrophies,http://dx.doi.org/10.1136/bjo.84.8.922,PMC1723576,,,,,"['HAFEZI, F', 'GRIMM, C', 'SIMMEN, B', 'WENZEL, A', 'REME, C']",,,,
,PMC,Vaccinia virus infection disrupts microtubule organization and centrosome function,http://dx.doi.org/10.1093/emboj/19.15.3932,PMC306617,,,"We examined the role of the microtubule cytoskeleton during vaccinia virus infection. We found that newly assembled virus particles accumulate in the vicinity of the microtubule-organizing centre in a microtubule- and dynein–dynactin complex-dependent fashion. Microtubules are required for efficient intracellular mature virus (IMV) formation and are essential for intracellular enveloped virus (IEV) assembly. As infection proceeds, the microtubule cytoskeleton becomes dramatically reorganized in a fashion reminiscent of overexpression of microtubule-associated proteins (MAPs). Consistent with this, we report that the vaccinia proteins A10L and L4R have MAP-like properties and mediate direct binding of viral cores to microtubules in vitro. In addition, vaccinia infection also results in severe reduction of proteins at the centrosome and loss of centrosomal microtubule nucleation efficiency. This represents the first example of viral-induced disruption of centrosome function. Further studies with vaccinia will provide insights into the role of microtubules during viral pathogenesis and regulation of centrosome function.",,"['Ploubidou, Aspasia', 'Moreau, Violaine', 'Ashman, Keith', 'Reckmann, Inge', 'González, Cayetano', 'Way, Michael']",,,,
,PMC,Coronavirus-Induced Demyelination Occurs in the Absence of Inducible Nitric Oxide Synthase,,PMC112293,,,"Demyelination induced by mouse hepatitis virus (MHV), strain JHM, is in large part immune mediated, but little is known about the mechanisms involved in this process. Previous results suggest that inducible nitric oxide synthase (NOS2) contributes transiently to MHV-induced demyelination. Herein, we show that equivalent amounts of demyelination were evident at day 12 after MHV infection in mice genetically deficient in NOS2 (NOS2(−/−)) and in C57BL/6 mice. Furthermore, using an established adoptive transfer model and pharmacological inhibitors of NOS2 function, we could demonstrate no effect on MHV-induced demyelination. These results indicate that NOS2 function is not required for demyelination in mice infected with MHV.",,"['Wu, Gregory F.', 'Pewe, Lecia', 'Perlman, Stanley']",,,,
,PMC,Characterization of an Essential RNA Secondary Structure in the 3′ Untranslated Region of the Murine Coronavirus Genome,,PMC112208,,,"We have previously identified a functionally essential bulged stem-loop in the 3′ untranslated region of the positive-stranded RNA genome of mouse hepatitis virus. This 68-nucleotide structure is composed of six stem segments interrupted by five bulges, and its structure, but not its primary sequence, is entirely conserved in the related bovine coronavirus. The functional importance of individual stem segments of this stem-loop was characterized by genetic analysis using targeted RNA recombination. We also examined the effects of stem segment mutations on the replication of mouse hepatitis virus defective interfering RNAs. These studies were complemented by enzymatic and chemical probing of the stem-loop. Taken together, our results confirmed most of the previously proposed structure, but they revealed that the terminal loop and an internal loop are larger than originally thought. Three of the stem segments were found to be essential for viral replication. Further, our results suggest that the stem segment at the base of the stem-loop is an alternative base-pairing structure for part of a downstream, and partially overlapping, RNA pseudoknot that has recently been shown to be necessary for bovine coronavirus replication.",,"['Hsue, Bilan', 'Hartshorne, Toinette', 'Masters, Paul S.']",,,,
,PMC,Mutational study reveals that tertiary interactions are conserved in ribosomal frameshifting pseudoknots of two luteoviruses.,,PMC1369989,,,"Expression of the putative replicase of potato leafroll virus (PLRV) is regulated by -1 ribosomal frameshifting in which a primary viral transcript has two overlapping open reading frames (ORFs). A region of 39 nt at the junction of the two ORFs is essential for frameshifting to occur. It has been shown to harbor two signals, one active on the level of the primary structure, termed the slippery sequence, and one component that forms a secondary or tertiary level structure, described as either a pseudoknot or a stem-loop motif. We have performed extensive site-directed mutagenesis of the frameshifting region and analyzed individual mutants for their ability to promote -1 frameshifting in vitro. Detailed comparison of our results with analogous mutants in the frameshifting region of the evolutionarily related beet western yellow virus, for which a crystal structure is available, unequivocally argues for the pseudoknot to be the structural motif necessary for the frameshifting function in PLRV transcripts. Mutations in PLRV that affect putative pseudoknot-specific tertiary-base interactions drastically affect frameshifting activity. In addition, a specific deletion mutant was identified that displayed PLRV wild-type frameshifting activity with only 22 nt available for pseudoknot formation.",,"['Kim, Y G', 'Maas, S', 'Wang, S C', 'Rich, A']",,,,
,PMC,Comparison of Cryptosporidium parvum Viability and Infectivity Assays following Ozone Treatment of Oocysts,,PMC92099,,,"Several in vitro surrogates have been developed as convenient, user-friendly alternatives to mouse infectivity assays for determining the viability of Cryptosporidium parvum oocysts. Such viability assays have been used increasingly to determine oocyst inactivation following treatment with chemical, physical, or environmental stresses. Defining the relationship between in vitro viability assays and oocyst infectivity in susceptible hosts is critical for determining the significance of existing oocyst inactivation data for these in vitro assays and their suitability in future studies. In this study, four viability assays were compared with mouse infectivity assays, using neonatal CD-1 mice. Studies were conducted in the United States and United Kingdom using fresh (<1 month) or environmentally aged (3 months at 4°C) oocysts, which were partially inactivated by ozonation before viability and/or infectivity analyses. High levels of variability were noted within and between the viability and infectivity assays in the U.S. and United Kingdom studies despite rigorous control over oocyst conditions and disinfection experiments. Based on the viability analysis of oocyst subsamples from each ozonation experiment, SYTO-59 assays demonstrated minimal change in oocyst viability, whereas 4′,6′-diamidino-2-phenylindole–propidium iodide assays, in vitro excystation, and SYTO-9 assays showed a marginal reduction in oocyst viability. In contrast, the neonatal mouse infectivity assay demonstrated significantly higher levels of oocyst inactivation in the U.S. and United Kingdom experiments. These comparisons illustrate that four in vitro viability assays cannot be used to reliably predict oocyst inactivation following treatment with low levels of ozone. Neonatal mouse infectivity assays should continue to be regarded as a “gold standard” until suitable alternative viability surrogates are identified for disinfection studies.",,"['Bukhari, Z.', 'Marshall, M. M.', 'Korich, D. G.', 'Fricker, C. R.', 'Smith, H. V.', 'Rosen, J.', 'Clancy, J. L.']",,,,
,PMC,Retrospective serological survey of antibodies to porcine circovirus type 1 and type 2.,,PMC1189611,,,"A retrospective serological survey was performed to determine the presence of antibodies to porcine circovirus type 1 (PCV1) and porcine circovirus type 2 (PCV2) in serum samples collected from sows at slaughterhouses in Canada in 1985, 1989, and 1997. Each serum sample was tested by indirect immunofluorescence on PCV-free PK15 cells, on PCV1-infected PK15 cells and on PCV2-infected PK15 cells. For the 3 years studied, sera positive to PCV1 and PCV2 were identified and the number of sera positive for PCV2 was greater than the number of sera positive for PCV1. The results indicated 1) that PCV2 appears to be the main PCV type circulating in the Canadian pig population, 2) that PCV2 had been circulating in the Canadian pig population at least 10 years before the postweaning multisystemic wasting syndrome (PMWS) was reported, and 3) that serological evaluation using PCV1 underestimates the seroprevalence of PCV2.",,"['Magar, R', 'Müller, P', 'Larochelle, R']",,,,
,PMC,"Bovine viral diarrhea viral infections in feeder calves with respiratory disease: interactions with Pasteurella spp., parainfluenza-3 virus, and bovine respiratory syncytial virus.",,PMC1189606,,,"The prevalence of bovine viral diarrhea virus (BVDV) infections was determined in a group of stocker calves suffering from acute respiratory disease. The calves were assembled after purchase from Tennessee auctions and transported to western Texas. Of the 120 calves, 105 (87.5%) were treated for respiratory disease. Sixteen calves died during the study (13.3%). The calves received a modified live virus BHV-1 vaccine on day 0 of the study. During the study, approximately 5 wk in duration, sera from the cattle, collected at weekly intervals, were tested for BVDV by cell culture. Sera were also tested for neutralizing antibodies to BVDV types 1 and 2, bovine herpesvirus-1 (BHV-1), parainfluenza-3 virus (PI-3V), and bovine respiratory syncytial virus (BRSV). The lungs from the 16 calves that died during the study were collected and examined by histopathology, and lung homogenates were inoculated onto cell cultures for virus isolation. There were no calves persistently infected with BVDV detected in the study, as no animals were viremic on day 0, nor were any animals viremic at the 2 subsequent serum collections. There were, however, 4 animals with BVDV type 1 noncytopathic (NCP) strains in the sera from subsequent collections. Viruses were isolated from 9 lungs: 7 with PI-3V, 1 with NCP BVDV type 1, and 1 with both BVHV-1 and BVDV. The predominant bacterial species isolated from these lungs was Pasteurella haemolytica serotype 1. There was serologic evidence of infection with BVDV types 1 and 2, PI-3V, and BRSV, as noted by seroconversion (> or = 4-fold rise in antibody titer) in day 0 to day 34 samples collected from the 104 survivors: 40/104 (38.5%) to BVDV type 1; 29/104 (27.9%) to BVDV type 2; 71/104 (68.3%) to PI-3V; and 81/104 (77.9%) to BRSV. In several cases, the BVDV type 2 antibody titers may have been due to crossreacting BVDV type 1 antibodies; however, in 7 calves the BVDV type 2 antibodies were higher, indicating BVDV type 2 infection. At the outset of the study, the 120 calves were at risk (susceptible to viral infections) on day 0 because they were seronegative to the viruses: 98/120 (81.7%), < 1:4 to BVDV type 1; 104/120 (86.7%) < 1:4 to BVDV type 2; 86/120 (71.7%) < 1:4 to PI-3V; 87/120 (72.5%) < 1:4 to BRSV; and 111/120 (92.5%) < 1:10 to BHV-1. The results of this study indicate that BVDV types 1 and 2 are involved in acute respiratory disease of calves with pneumonic pasteurellosis. The BVDV may be detected by virus isolation from sera and/or lung tissues and by serology. The BVDV infections occurred in conjunction with infections by other viruses associated with respiratory disease, namely, PI-3V and BRSV. These other viruses may occur singly or in combination with each other. Also, the study indicates that purchased calves may be highly susceptible, after weaning, to infections by BHV-1, BVDV types 1 and 2, PI-3V, and BRSV early in the marketing channel.",,"['Fulton, R W', 'Purdy, C W', 'Confer, A W', 'Saliki, J T', 'Loan, R W', 'Briggs, R E', 'Burge, L J']",,,,
,PMC,Development of a Recombinant Nucleoprotein-Based Enzyme-Linked Immunosorbent Assay for Quantification of Antibodies against  Porcine Reproductive and Respiratory Syndrome Virus,,PMC95938,,,"A rapid, inexpensive enzyme-linked immunosorbent assay (ELISA) to quantitate antibodies to porcine respiratory and reproductive syndrome virus (PRRSV) in serum was developed using a recombinant PRRSV nucleoprotein (rN). The sensitivity (85.3%) and specificity (81.7%) of the Kansas State University ELISA were good, correlating well (82.4%) with the IDEXX HerdChek ELISA.",,"['Witte, Steven B.', 'Chard-Bergstrom, Cindy', 'Loughin, Thomas A.', 'Kapil, Sanjay']",,,,
,PMC,Primary Structure of the Sialodacryoadenitis Virus Genome: Sequence of the Structural-Protein Region and Its Application for Differential Diagnosis,,PMC95915,,,"Sialodacryoadenitis virus (SDAV) is a coronavirus that is commonly found in laboratory rats and that causes sialodacryoadenitis and respiratory illness. We cloned and sequenced the 3′ terminal 9.8 kb of the genomic RNA and analyzed the structure of the viral genome. As with mouse hepatitis coronaviruses (MHVs), the SDAV genome was able to code for a spike protein, a small membrane protein, a membrane-associated protein, and a nucleocapsid protein. In addition, the hemagglutinin-esterase gene capable of encoding a protein of 439 amino acids (aa) was identified. The putative functional site for acetylesterase activity was present in the HE protein as Phe-Gly-Asp-Ser (FGDS), suggesting that the SDAV HE protein might have retained the esterase activity. Immediately upstream of the HE gene and downstream of the polymerase 1b gene, the NS2 nonstructural-protein gene was identified with a coding capacity of 274 aa. A motif of UCUAAAC was identified as a potential transcription signal for subgenomic mRNA synthesis. Large insertions of 172, 127, and 44 aa were detected in the N-terminal half of the predicted S protein of SDAV when its sequence was compared to the sequences of MHV 2, MHV JHM, and MHV A59, respectively. The sequence information on the SDAV S-protein gene was applied to a differential diagnostic PCR to detect and distinguish the rat coronavirus from mouse coronaviruses. This is the first report on the comprehensive genetic information of any rat coronavirus.",,"['Yoo, Dongwan', 'Pei, Yanlong', 'Christie, Natasha', 'Cooper, Melissa']",,,,
,PMC,"Full Capacity of Recombinant Escherichia coli Heat-Stable Enterotoxin Fusion Proteins for Extracellular Secretion, Antigenicity, Disulfide Bond Formation, and Activity",,PMC101696,,,"We have successfully used the major subunit ClpG of Escherichia coli CS31A fimbriae as an antigenic and immunogenic exposure-delivery vector for various heterologous peptides varying in nature and length. However, the ability of ClpG as a carrier to maintain in vitro and in vivo the native biological properties of passenger peptide has not yet been reported. To address this possibility, we genetically fused peptides containing all or part of the E. coli human heat-stable enterotoxin (STh) sequence to the amino or carboxyl ends of ClpG. Using antibodies to the ClpG and STh portions for detecting the hybrids; AMS (4-acetamido-4′-maleimidylstilbene-2,2′-disulfonate), a potent free thiol-trapping reagent, for determining the redox state of STh in the fusion; and the suckling mouse assay for enterotoxicity, we demonstrated that all ClpG-STh proteins were secreted in vitro and in vivo outside the E. coli cells in a heat-stable active oxidized (disulfide-bonded) form. Indeed, in contrast to many earlier studies, blocking the natural NH(2) or COOH extremities of STh had, in all cases, no drastic effect on cell release and toxin activity. Only antigenicity of STh C-terminally extended with ClpG was strongly affected in a conformation-dependent manner. These results suggest that the STh activity was not altered by the chimeric structure, and therefore that, like the natural toxin, STh in the fusion had a spatial structure flexible enough to be compatible with secretion and enterotoxicity (folding and STh receptor recognition). Our study also indicates that disulfide bonds were essential for enterotoxicity but not for release, that spontaneous oxidation by molecular oxygen occurred in vitro in the medium, and that the E. coli cell-bound toxin activity in vivo resulted from an effective export processing of hybrids and not cell lysis. None of the ClpG-STh subunits formed hybrid CS31A-STh fimbriae at the cell surface of E. coli, and a strong decrease in the toxin activity was observed in the absence of CS31A helper proteins. In fact, chimeras translocated across the outer membrane as a free folded monomer once they were guided into the periplasm by the ClpG leader peptide through the CS31A-dependent secretory pathway. In summary, ClpG appears highly attractive as a carrier reporter protein for basic and applied research through the engineering of E. coli for culture supernatant delivery of an active cysteine-containing protein, such as the heat-stable enterotoxin.",,"['Batisson, Isabelle', 'Der Vartanian, Maurice', 'Gaillard-Martinie, Brigitte', 'Contrepois, Michel']",,,,
,PMC,Molecular Characterization of an Avian Astrovirus,,PMC112117,,,"Astroviruses are known to cause enteric disease in several animal species, including turkeys. However, only human astroviruses have been well characterized at the nucleotide level. Herein we report the nucleotide sequence, genomic organization, and predicted amino acid sequence of a turkey astrovirus isolated from poults with an emerging enteric disease.",,"['Koci, Matthew D.', 'Seal, Bruce S.', 'Schultz-Cherry, Stacey']",,,,
,PMC,Depletion of Lymphocytes and Diminished Cytokine Production in Mice Infected with a Highly Virulent Influenza A (H5N1) Virus Isolated from Humans,,PMC112109,,,"Previously, we observed that several virulent influenza A (H5N1) viruses which caused severe or fatal disease in humans were also lethal in BALB/c mice following dissemination of the virus to solid organs, including the brain. In contrast, one particular human H5N1 virus was nonlethal in mice and showed no evidence of systemic spread. To compare H5N1 viruses of varying pathogenicity for their ability to alter the mammalian immune system, mice were infected with either influenza A/Hong Kong/483/97 (HK/483) (lethal) or A/Hong Kong/486/97 (HK/486) (nonlethal) virus and monitored for lymphocyte depletion in the blood, lungs, and lymphoid tissue. Intranasal infection with HK/483 resulted in a significant decrease in the total number of circulating leukocytes evident as early as day 2 postinfection. Differential blood counts demonstrated up to an 80% drop in lymphocytes by day 4 postinfection. In contrast, nonlethal HK/486-infected mice displayed only a transient drop of lymphocytes during the infectious period. Analysis of lung and lymphoid tissue from HK/483-infected mice demonstrated a reduction in the number of CD4(+) and CD8(+) T cells and reduced synthesis of the cytokines interleukin-1β and gamma interferon and the chemokine macrophage inflammatory protein compared with HK/486-infected mice. In contrast, the cytokine and chemokine levels were increased in the brains of mice infected with HK/483 but not HK/486. Evidence of apoptosis in the spleen and lung of HK/483-infected mice was detected in situ, suggesting a mechanism for lymphocyte destruction. These results suggest that destructive effects on the immune system may be one factor that contributes to the pathogenesis of H5N1 viruses in mammalian hosts.",,"['Tumpey, Terrence M.', 'Lu, Xiuhua', 'Morken, Timothy', 'Zaki, Sherif R.', 'Katz, Jacqueline M.']",,,,
,PMC,Exacerbation of Autoantibody-Mediated Hemolytic  Anemia by Viral Infection,,PMC112102,,,"Strong enhancement of the pathogenicity of an antierythrocyte monoclonal antibody was observed after infection of mice with lactate dehydrogenase-elevating virus. While injection of the antierythrocyte antibody alone induced only moderate anemia, concomitant infection with this virus, which is harmless in most normal mice, led to a dramatic drop in the hematocrit and to death of infected animals. In vitro and in vivo analyses showed a dramatic increase in the ability of macrophages from infected mice to phagocytose antibody-coated erythrocytes. These results indicate that viruses can trigger the onset of autoimmune disease by enhancing the pathogenicity of autoantibodies. They may explain how unrelated viruses could be implicated in the etiology of autoantibody-mediated autoimmune diseases.",,"['Meite, Mory', 'Léonard, Sabine', 'Idrissi, Mohammed El Azami El', 'Izui, Shozo', 'Masson, Pierre L.', 'Coutelier, Jean-Paul']",,,,
,PMC,A Positive-Strand RNA Virus with Three Very Different Subgenomic RNA Promoters,,PMC112095,,,"Numerous RNA viruses generate subgenomic mRNAs (sgRNAs) for expression of their 3′-proximal genes. A major step in control of viral gene expression is the regulation of sgRNA synthesis by specific promoter elements. We used barley yellow dwarf virus (BYDV) as a model system to study transcriptional control in a virus with multiple sgRNAs. BYDV generates three sgRNAs during infection. The sgRNA1 promoter has been mapped previously to a 98-nucleotide (nt) region which forms two stem-loop structures. It was determined that sgRNA1 is not required for BYDV RNA replication in oat protoplasts. In this study, we show that neither sgRNA2 nor sgRNA3 is required for BYDV RNA replication. The promoters for sgRNA2 and sgRNA3 synthesis were mapped by using deletion mutagenesis. The minimal sgRNA2 promoter is approximately 143 nt long (nt 4810 to 4952) and is located immediately downstream of the putative sgRNA2 start site (nt 4809). The minimal sgRNA3 core promoter is 44 nt long (nt 5345 to 5388), with most of the sequence located downstream of sgRNA3 start site (nt 5348). For both promoters, additional sequences upstream of the start site enhanced sgRNA promoter activity. These promoters contrast to the sgRNA1 promoter, in which almost all of the promoter is located upstream of the transcription initiation site. Comparison of RNA sequences and computer-predicted secondary structures revealed little or no homology between the three sgRNA promoter elements. Thus, a small RNA virus with multiple sgRNAs can have very different subgenomic promoters, which implies a complex system for promoter recognition and regulation of subgenomic RNA synthesis.",,"['Koev, Gennadiy', 'Miller, W. Allen']",,,,
,PMC,"Growth, Adipose, Brain, and Skin Alterations Resulting from Targeted Disruption of the Mouse Peroxisome  Proliferator-Activated Receptor β(δ)",,PMC85961,,,"To determine the physiological roles of peroxisome proliferator-activated receptor β (PPARβ), null mice were constructed by targeted disruption of the ligand binding domain of the murine PPARβ gene. Homozygous PPARβ-null term fetuses were smaller than controls, and this phenotype persisted postnatally. Gonadal adipose stores were smaller, and constitutive mRNA levels of CD36 were higher, in PPARβ-null mice than in controls. In the brain, myelination of the corpus callosum was altered in PPARβ-null mice. PPARβ was not required for induction of mRNAs involved in epidermal differentiation induced by O-tetradecanoylphorbol-13-acetate (TPA). The hyperplastic response observed in the epidermis after TPA application was significantly greater in the PPARβ-null mice than in controls. Inflammation induced by TPA in the skin was lower in wild-type mice fed sulindac than in similarly treated PPARβ-null mice. These results are the first to provide in vivo evidence of significant roles for PPARβ in development, myelination of the corpus callosum, lipid metabolism, and epidermal cell proliferation.",,"['Peters, Jeffrey M.', 'Lee, Susanna S. T.', 'Li, Wen', 'Ward, Jerrold M.', 'Gavrilova, Oksana', 'Everett, Carrie', 'Reitman, Marc L.', 'Hudson, Lynn D.', 'Gonzalez, Frank J.']",,,,
,PMC,The human coronavirus 229E superfamily 1 helicase has RNA and DNA duplex-unwinding activities with 5'-to-3' polarity.,,PMC1369980,,,"The human coronavirus 229E replicase gene encodes a protein, p66HEL, that contains a putative zinc finger structure linked to a putative superfamily (SF) 1 helicase. A histidine-tagged form of this protein, HEL, was expressed using baculovirus vectors in insect cells. The purified recombinant protein had in vitro ATPase activity that was strongly stimulated by poly(U), poly(dT), poly(C), and poly(dA), but not by poly(G). The recombinant protein also had both RNA and DNA duplex-unwinding activities with 5'-to-3' polarity. The DNA helicase activity of the enzyme preferentially unwound 5'-oligopyrimidine-tailed, partial-duplex substrates and required a tail length of at least 10 nucleotides for effective unwinding. The combined data suggest that the coronaviral SF1 helicase functionally differs from the previously characterized RNA virus SF2 helicases.",,"['Seybert, A', 'Hegyi, A', 'Siddell, S G', 'Ziebuhr, J']",,,,
,PMC,The burden of childhood asthma,http://dx.doi.org/10.1136/adc.82.suppl_2.ii2,PMC1765082,,,"Paediatric asthma is a major clinical concern worldwide and represents a huge burden on family and society. It accounts for a large number of lost school days and may deprive the child of both academic achievement and social interaction. Childhood asthma also places strain on healthcare resources as a result of doctor and hospital visits and the cost of treatment. The prevalence of asthma varies worldwide, possibly because of different exposure to respiratory infection, indoor and outdoor pollution, and diet. Certain risk factors appear to predispose children to developing asthma and atopic disease, including incidence and severity of wheezing, atopy, maternal smoking, and number of fever episodes. This paper discusses the burden, prevalence, and risk factors associated with paediatric asthma.",,"von Mutius, E.",,,,
,PMC,QUIZ CORNER,,PMC1476222,,,,,,,,,
,PMC,Mucosal and Systemic Immune Responses to Chimeric Fimbriae Expressed by Salmonella enterica Serovar  Typhimurium Vaccine Strains,,PMC97544,,,"Recombinant live oral vaccines expressing pathogen-derived antigens offer a unique set of attractive properties. Among these are the simplicity of administration, the capacity to induce mucosal and systemic immunity, and the advantage of permitting genetic manipulation for optimal antigen presentation. In this study, the benefit of having a heterologous antigen expressed on the surface of a live vector rather than intracellularly was evaluated. Accordingly, the immune response of mice immunized with a Salmonella enterica serovar Typhimurium vaccine strain expressing the Escherichia coli 987P fimbrial antigen on its surface (Fas(+)) was compared with the expression in the periplasmic compartment (Fas(−)). Orally immunized BALB/c mice showed that 987P fimbriated Salmonella serovar Typhimurium CS3263 (aroA asd) with pCS151 (fas(+) asd(+)) elicited a significantly higher level of 987P-specific systemic immunoglobulin G (IgG) and mucosal IgA than serovar Typhimurium CS3263 with pCS152 (fasD mutant, asd(+)) expressing 987P periplasmic antigen. Further studies were aimed at determining whether the 987P fimbriae expressed by serovar Typhimurium χ4550 (cya crp asd) could be used as carriers of foreign epitopes. For this, the vaccine strain was genetically engineered to express chimeric fimbriae carrying the transmissible gastroenteritis virus (TGEV) C (379-388) and A (521-531) epitopes of the spike protein inserted into the 987P major fimbrial subunit FasA. BALB/c mice administered orally serovar Typhimurium χ4550 expressing the chimeric fimbriae from the tet promoter in pCS154 (fas(+) asd(+)) produced systemic antibodies against both fimbria and the TGEV C epitope but not against the TGEV A epitope. To improve the immunogenicity of the chimeric fimbriae, the in vivo inducible nirB promoter was inserted into pCS154, upstream of the fas genes, to create pCS155. In comparison with the previously used vaccine, BALB/c mice immunized orally with serovar Typhimurium χ4550/pCS155 demonstrated significantly higher levels of serum IgG and mucosal IgA against 987P fimbria. Moreover, mucosal IgA against the TGEV C epitope was only detected with serovar Typhimurium χ4550/pCS155. The induced antibodies also recognized the epitopes in the context of the full-length TGEV spike protein. Hence, immune responses to heterologous chimeric fimbriae on Salmonella vaccine vectors can be optimized by using promoters known to be activated in vivo.",,"['Chen, Huaiqing', 'Schifferli, Dieter M.']",,,,
,PMC,Mouse Hepatitis Virus Replicase Proteins Associate with Two Distinct Populations of Intracellular Membranes,,PMC112052,,,"The coronavirus replicase gene (gene 1) is translated into two co-amino-terminal polyproteins that are proteolytically processed to yield more than 15 mature proteins. Several gene 1 proteins have been shown to localize at sites of viral RNA synthesis in the infected cell cytoplasm, notably on late endosomes at early times of infection. However, both immunofluorescence and electron microscopic studies have also detected gene 1 proteins at sites distinct from the putative sites of viral RNA synthesis or virus assembly. In this study, mouse hepatitis virus (MHV)-infected cells were fractionated and analyzed to determine if gene 1 proteins segregated to more than one membrane population. Following differential centrifugation of lysates of MHV-infected DBT cells, gene 1 proteins as well as the structural N and M proteins were detected almost exclusively in a high-speed small membrane pellet. Following fractionation of the small membrane pellet on an iodixanol density gradient, the gene 1 proteins p28 and helicase cofractionated with dense membranes (1.12 to 1.13 g/ml) that also contained peak concentrations of N. In contrast, p65 and p1a-22 were detected in a distinct population of less dense membranes (1.05 to 1.09 g/ml). Viral RNA was detected in membrane fractions containing helicase, p28, and N but not in the fractions containing p65 and p1a-22. LAMP-1, a marker for late endosomes and lysosomes, was detected in both membrane populations. These results demonstrate that multiple gene 1 proteins segregate into two biochemically distinct but tightly associated membrane populations and that only one of these populations appears to be a site for viral RNA synthesis. The results further suggest that p28 is a component of the viral replication complex whereas the gene 1 proteins p1a-22 and p65 may serve roles during infection that are distinct from viral RNA transcription or replication.",,"['Sims, Amy C.', 'Ostermann, Joachim', 'Denison, Mark R.']",,,,
,PMC,Identification by Phage Display and Characterization of Two Neutralizing Chimpanzee Monoclonal Antibodies  to the Hepatitis E Virus Capsid Protein,,PMC112041,,,"Two monoclonal antibodies (MAbs) against the ORF2 protein of the SAR-55 strain of hepatitis E virus (HEV) were isolated by phage display from a cDNA library of chimpanzee (Pan troglodytes) γ1/κ antibody genes. Both MAbs, HEV#4 and HEV#31, bound to reduced, denatured open reading frame 2 (ORF2) protein in a Western blot, suggesting that they recognize linear epitopes. The affinities (equilibrium dissociation constants, K(d)) for the SAR-55 ORF2 protein were 1.7 nM for HEV#4 and 5.4 nM for HEV#31. The two MAbs also reacted in an enzyme-linked immunosorbent assay with recombinant ORF2 protein from a heterologous HEV, the Meng strain. Each MAb blocked the subsequent binding of the other MAb to homologous ORF2 protein in indirect competition assays, suggesting that they recognize the same or overlapping epitopes. Radioimmunoprecipitation assays suggested that at least part of the linear epitope(s) recognized by the two MAbs is located between amino acids 578 and 607. MAbs were mixed with homologous HEV in vitro and then inoculated into rhesus monkeys (Macaca mulatta) to determine their neutralizing ability. Whereas all control animals developed hepatitis (elevated liver enzyme levels in serum) and seroconverted to HEV, those receiving an inoculum incubated with either HEV#4 or HEV#31 were not infected. Therefore, each MAb neutralized the SAR-55 strain of HEV in vitro.",,"['Schofield, D. J.', 'Glamann, J.', 'Emerson, S. U.', 'Purcell, R. H.']",,,,
,PMC,Rubella Virus Nonstructural Protein Protease Domains Involved in trans- and cis-Cleavage Activities,,PMC112025,,,"Rubella virus (RV) genomic RNA contains two large open reading frames (ORFs): a 5′-proximal ORF encoding nonstructural proteins (NSPs) that function primarily in viral RNA replication and a 3′-proximal ORF encoding the viral structural proteins. Proteolytic processing of the RV NSP ORF translation product p200 is essential for viral replication. Processing of p200 to two mature products (p150 and p90) in the order NH(2)-p150-p90-COOH is carried out by an RV-encoded protease residing in the C-terminal region of p150. The RV nonstructural protease (NS-pro) belongs to a viral papain-like protease family that cleaves the polyprotein both in trans and in cis. A conserved X domain of unknown function was found from previous sequence analysis to be associated with NS-pro. To define the domains responsible for cis- and trans-cleavage activities and the function of the X domain in terms of protease activity, an in vitro translation system was employed. We demonstrated that the NSP region from residue 920 to 1296 is necessary for trans-cleavage activity. The domain from residue 920 to 1020 is not required for cis-cleavage activity. The X domain located between residues 834 and 940, outside the regions responsible for both cis- and trans-cleavage activities of NS-pro, was found to be important for NS-pro trans-cleavage activity but not for cis-cleavage activity. Analysis of sequence homology and secondary structure of the RV NS-pro catalytic region reveals a folding structure similar to that of papain.",,"['Liang, Yuying', 'Yao, Jiansheng', 'Gillam, Shirley']",,,,
,PMC,"The Predicted Metal-Binding Region of the Arterivirus Helicase Protein Is Involved in Subgenomic mRNA Synthesis,  Genome Replication, and Virion Biogenesis",,PMC110875,,,"Equine arteritis virus (EAV), the prototype Arterivirus, is a positive-stranded RNA virus that expresses its replicase in the form of two large polyproteins of 1,727 and 3,175 amino acids. The functional replicase subunits (nonstructural proteins), which drive EAV genome replication and subgenomic mRNA transcription, are generated by extensive proteolytic processing. Subgenomic mRNA transcription involves an unusual discontinuous step and generates the mRNAs for structural protein expression. Previously, the phenotype of mutant EAV030F, which carries a single replicase point mutation (Ser-2429→Pro), had implicated the nsp10 replicase subunit (51 kDa) in viral RNA synthesis, and in particular in subgenomic mRNA transcription. nsp10 contains an N-terminal (putative) metal-binding domain (MBD), located just upstream of the Ser-2429→Pro mutation, and a helicase activity in its C-terminal part. We have now analyzed the N-terminal domain of nsp10 in considerable detail. A total of 38 mutants, most of them carrying specific single point mutations, were tested in the context of an EAV infectious cDNA clone. Variable effects on viral genome replication and subgenomic mRNA transcription were observed. In general, our results indicated that the MBD region, and in particular a set of 13 conserved Cys and His residues that are assumed to be involved in zinc binding, is essential for viral RNA synthesis. On the basis of these data and comparative sequence analyses, we postulate that the MBD may employ a rather unusual mode of zinc binding that could result in the association of up to four zinc cations with this domain. The region containing residue Ser-2429 may play the role of “hinge spacer,” which connects the MBD to the rest of nsp10. Several mutations in this region specifically affected subgenomic mRNA synthesis. Furthermore, one of the MBD mutants was replication and transcription competent but did not produce infectious progeny virus. This suggests that nsp10 is involved in an as yet unidentified step of virion biogenesis.",,"['van Dinten, Leonie C.', 'van Tol, Hans', 'Gorbalenya, Alexander E.', 'Snijder, Eric J.']",,,,
,PMC,Host Protein Interactions with the 3′ End of Bovine Coronavirus  RNA and the Requirement of the Poly(A) Tail for Coronavirus Defective Genome Replication,,PMC110857,,,"RNA viruses have 5′ and 3′ untranslated regions (UTRs) that contain specific signals for RNA synthesis. The coronavirus genome is capped at the 5′ end and has a 3′ UTR that consists of 300 to 500 nucleotides (nt) plus a poly(A) tail. To further our understanding of coronavirus replication, we have begun to examine the involvement of host factors in this process for two group II viruses, bovine coronavirus (BCV) and mouse hepatitis coronavirus (MHV). Specific host protein interactions with the BCV 3′ UTR [287 nt plus poly(A) tail] were identified using gel mobility shift assays. Competition with the MHV 3′ UTR [301 nt plus poly(A) tail] suggests that the interactions are conserved for the two viruses. Proteins with molecular masses of 99, 95, and 73 kDa were detected in UV cross-linking experiments. Less heavily labeled proteins were also detected in the ranges of 40 to 50 and 30 kDa. The poly(A) tail was required for binding of the 73-kDa protein. Immunoprecipitation of UV-cross-linked proteins identified the 73-kDa protein as the cytoplasmic poly(A)-binding protein (PABP). Replication of the defective genomes BCV Drep and MHV MIDI-C, along with several mutants, was used to determine the importance of the poly(A) tail. Defective genomes with shortened poly(A) tails consisting of 5 or 10 A residues were replicated after transfection into helper virus-infected cells. BCV Drep RNA that lacked a poly(A) tail did not replicate, whereas replication of MHV MIDI-C RNA with a deleted tail was detected after several virus passages. All mutants exhibited delayed kinetics of replication. Detectable extension or addition of the poly(A) tail to the mutants correlated with the appearance of these RNAs in the replication assay. RNAs with shortened poly(A) tails exhibited less in vitro PABP binding, suggesting that decreased interactions with the protein may affect RNA replication. The data strongly indicate that the poly(A) tail is an important cis-acting signal for coronavirus replication.",,"['Spagnolo, Jeannie F.', 'Hogue, Brenda G.']",,,,
,PMC,Assembly of the Coronavirus Envelope: Homotypic Interactions between the M Proteins,,PMC110848,,,"The viral membrane proteins M and E are the minimal requirements for the budding of coronavirus particles. Since the E protein occurs in particles only in trace amounts, the lateral interactions between the M proteins apparently generate the major driving force for envelope formation. By using coimmunoprecipitation and envelope incorporation assays, we provide extensive evidence for the existence of such M-M interactions. In addition, we determined which domains of the M protein are involved in this homotypic association, using a mutagenetic approach. Mutant M proteins which were not able to assemble into viruslike particles (VLPs) by themselves (C. A. M. de Haan, L. Kuo, P. S. Masters, H. Vennema, and P. J. M. Rottier, J. Virol. 72:6838–6850, 1998) were tested for the ability to associate with other M proteins and to be rescued into VLPs formed by assembly-competent M proteins. We found that M proteins lacking parts of the transmembrane cluster, of the amphipathic domain, or of the hydrophilic carboxy-terminal tail, or M proteins that had their luminal domain replaced by heterologous ectodomains, were still able to associate with assembly-competent M proteins, resulting in their coincorporation into VLPs. Only a mutant M protein in which all three transmembrane domains had been replaced lost this ability. The results indicate that M protein molecules interact with each other through multiple contact sites, particularly at the transmembrane level. Finally, we tested the stringency with which membrane proteins are selected for incorporation into the coronavirus envelope by probing the coassembly of some foreign proteins. The observed efficient exclusion from budding of the vesicular stomatitis virus G protein and the equine arteritis virus M protein indicates that envelope assembly is indeed a highly selective sorting process. The low but detectable incorporation of CD8 molecules, however, demonstrated that this process is not perfect.",,"['de Haan, Cornelis A. M.', 'Vennema, Harry', 'Rottier, Peter J. M.']",,,,
,PMC,Translational Control of Viral Gene Expression in Eukaryotes,,PMC98994,,,"As obligate intracellular parasites, viruses rely exclusively on the translational machinery of the host cell for the synthesis of viral proteins. This relationship has imposed numerous challenges on both the infecting virus and the host cell. Importantly, viruses must compete with the endogenous transcripts of the host cell for the translation of viral mRNA. Eukaryotic viruses have thus evolved diverse mechanisms to ensure translational efficiency of viral mRNA above and beyond that of cellular mRNA. Mechanisms that facilitate the efficient and selective translation of viral mRNA may be inherent in the structure of the viral nucleic acid itself and can involve the recruitment and/or modification of specific host factors. These processes serve to redirect the translation apparatus to favor viral transcripts, and they often come at the expense of the host cell. Accordingly, eukaryotic cells have developed antiviral countermeasures to target the translational machinery and disrupt protein synthesis during the course of virus infection. Not to be outdone, many viruses have answered these countermeasures with their own mechanisms to disrupt cellular antiviral pathways, thereby ensuring the uncompromised translation of virion proteins. Here we review the varied and complex translational programs employed by eukaryotic viruses. We discuss how these translational strategies have been incorporated into the virus life cycle and examine how such programming contributes to the pathogenesis of the host cell.",,"['Gale, Michael', 'Tan, Seng-Lai', 'Katze, Michael G.']",,,,
,PMC,CHARACTERIZATION OF MURINE CORONAVIRUS NEUTRALIZATION EPITOPES WITH PHAGE-DISPLAYED PEPTIDES,http://dx.doi.org/10.1006/viro.2000.0310,PMC3987775,,,"Phage-displayed peptide libraries were used to map immunologically-relevant epitopes on the surface (S) glycoprotein of a neurotropic murine coronavirus (MHV-A59). Three in vitro virus-neutralizing and in vivo protective mAbs against either continuous or discontinuous epitopes on the S glycoprotein were used to screen twelve different peptide libraries expressed on the pVIII major coat protein of the fd filamentous bacteriophage. Consensus sequences were identified that matched short sequences within the S glycoprotein. The sequence of a tight-binding, mAb-selected peptide suggested the location of a discontinuous epitope within the N-terminal S1 subunit. Several tightly-binding phage were amplified and used directly as immunogens in BALB/c and C57BL/6 mice. Partial protection of C57BL/6 mice against a lethal acute virus infection was achieved with a phage preparation that displayed a linear epitope. Protection correlated with the presence of sufficient levels of specific antiviral antibodies recognizing the same immunodominant domain and 13-mer peptide, located within the C-terminal S2 subunit, as the selecting mAb. Thus, the direct use of phage-displayed peptides to evaluate protective anti-viral immune responses complements their use to characterize antibody-binding epitopes. This is the first evaluation of protective immunization induced by mAb-selected phage-displayed peptides.",,"['Yu, Mathilde W. N.', 'Scott, Jamie K.', 'Fournier, Alain', 'Talbot, Pierre J.']",,,,
,PMC,The making of infectious viral RNA: No size limit in sight,,PMC33981,,,,,"Lai, Michael M. C.",,,,
,PMC,Engineering the largest RNA virus genome as an infectious bacterial artificial chromosome,,PMC25860,,,"The construction of cDNA clones encoding large-size RNA molecules of biological interest, like coronavirus genomes, which are among the largest mature RNA molecules known to biology, has been hampered by the instability of those cDNAs in bacteria. Herein, we show that the application of two strategies, cloning of the cDNAs into a bacterial artificial chromosome and nuclear expression of RNAs that are typically produced within the cytoplasm, is useful for the engineering of large RNA molecules. A cDNA encoding an infectious coronavirus RNA genome has been cloned as a bacterial artificial chromosome. The rescued coronavirus conserved all of the genetic markers introduced throughout the sequence and showed a standard mRNA pattern and the antigenic characteristics expected for the synthetic virus. The cDNA was transcribed within the nucleus, and the RNA translocated to the cytoplasm. Interestingly, the recovered virus had essentially the same sequence as the original one, and no splicing was observed. The cDNA was derived from an attenuated isolate that replicates exclusively in the respiratory tract of swine. During the engineering of the infectious cDNA, the spike gene of the virus was replaced by the spike gene of an enteric isolate. The synthetic virus replicated abundantly in the enteric tract and was fully virulent, demonstrating that the tropism and virulence of the recovered coronavirus can be modified. This demonstration opens up the possibility of employing this infectious cDNA as a vector for vaccine development in human, porcine, canine, and feline species susceptible to group 1 coronaviruses.",,"['Almazán, Fernando', 'González, José M.', 'Pénzes, Zoltan', 'Izeta, Ander', 'Calvo, Enrique', 'Plana-Durán, Juan', 'Enjuanes, Luis']",,,,
,PMC,Liver-Specific Alpha 2 Interferon Gene Expression Results in Protection from Induced Hepatitis,,PMC112004,,,"The current therapy for hepatitis B and C is based on systemic administration of recombinant human alpha interferon (r-hIFN-α). However, systemic delivery of r-hIFN-α is associated with severe side effects, but more importantly, it is effective in only a small percentage of patients. In an effort to maximize IFN-α antiviral efficacy, we have explored the therapeutic potential of murine IFN-α2 (mIFNα2) selectively expressed in the liver. To this end, we have developed a helper-dependent adenovirus vector (HD) containing the mIFN-α2 gene under the control of the liver-specific transthyretin promoter (HD-IFN). Comparison with a first-generation adenovirus carrying the same mIFN-α2 expression cassette indicates that at certain HD-IFN doses, induction of antiviral genes can be achieved in the absence of detectable circulating mIFN-α2. Challenge of injected mice with mouse hepatitis virus type 3 showed that HD-IFN provides high liver protection. Moreover, liver protection was also observed in acute nonviral liver inflammation hepatitis induced by concanavalin A at 1 month postinfection. These results hold promise for the development of a gene therapy treatment for chronic viral hepatitis based on liver-restricted expression of IFN-α2.",,"['Aurisicchio, Luigi', 'Delmastro, Paola', 'Salucci, Valentina', 'Paz, Odalys Gonzalez', 'Rovere, Patrizia', 'Ciliberto, Gennaro', 'La Monica, Nicola', 'Palombo, Fabio']",,,,
,PMC,Identification of a Key Target Sequence To Block Human Immunodeficiency Virus Type 1 Replication  within the gag-pol Transframe Domain,,PMC111982,,,"Although the full sequence of the human immunodeficiency virus type 1 (HIV-1) genome has been known for more than a decade, effective genetic antivirals have yet to be developed. Here we show that, of 22 regions examined, one highly conserved sequence (ACTCTTTGGCAACGA) near the 3′ end of the HIV-1 gag-pol transframe region, encoding viral protease residues 4 to 8 and a C-terminal Vpr-binding motif of p6(Gag) protein in two different reading frames, can be successfully targeted by an antisense peptide nucleic acid oligomer named PNA(PR2). A disrupted translation of gag-pol mRNA induced at the PNA(PR2)-annealing site resulted in a decreased synthesis of Pr160(Gag-Pol) polyprotein, hence the viral protease, a predominant expression of Pr55(Gag) devoid of a fully functional p6(Gag) protein, and the excessive intracellular cleavage of Gag precursor proteins, hindering the processes of virion assembly. Treatment with PNA(PR2) abolished virion production by up to 99% in chronically HIV-1-infected H9 cells and in peripheral blood mononuclear cells infected with clinical HIV-1 isolates with the multidrug-resistant phenotype. This particular segment of the gag-pol transframe gene appears to offer a distinctive advantage over other regions in invading viral structural genes and restraining HIV-1 replication in infected cells and may potentially be exploited as a novel antiviral genetic target.",,"['Sei, Shizuko', 'Yang, Quan-en', ""O'Neill, Dennis"", 'Yoshimura, Kazuhisa', 'Nagashima, Kunio', 'Mitsuya, Hiroaki']",,,,
,PMC,Identification of a cis-Acting Replication Element within  the Poliovirus Coding Region,,PMC111979,,,"The replication of poliovirus, a positive-stranded RNA virus, requires translation of the infecting genome followed by virus-encoded VPg and 3D polymerase-primed synthesis of a negative-stranded template. RNA sequences involved in the latter process are poorly defined. Since many sequences involved in picornavirus replication form RNA structures, we searched the genome, other than the untranslated regions, for predicted local secondary structural elements and identified a 61-nucleotide (nt) stem-loop in the region encoding the 2C protein. Covariance analysis suggested the structure was well conserved in the Enterovirus genus of the Picornaviridae. Site-directed mutagenesis, disrupting the structure without affecting the 2C product, destroyed genome viability and suggested that the structure was required in the positive sense for function. Recovery of revertant viruses suggested that integrity of the structure was critical for function, and analysis of replication demonstrated that nonviable mutants did not synthesize negative strands. Our conclusion, that this RNA secondary structure constitutes a novel poliovirus cis-acting replication element (CRE), is supported by the demonstration that subgenomic replicons bearing lethal mutations in the native structure can be restored to replication competence by the addition of a second copy of the 61-nt wild-type sequence at another location within the genome. This poliovirus CRE functionally resembles an element identified in rhinovirus type 14 (K. L. McKnight and S. M. Lemon, RNA 4:1569–1584, 1998) and the cardioviruses (P. E. Lobert, N. Escriou, J. Ruelle, and T. Michiels, Proc. Natl. Acad. Sci. USA 96:11560–11565, 1999) but differs in sequence, structure, and location. The functional role and evolutionary significance of CREs in the replication of positive-sense RNA viruses is discussed.",,"['Goodfellow, Ian', 'Chaudhry, Yasmin', 'Richardson, Andrew', 'Meredith, Janet', 'Almond, Jeffrey W.', 'Barclay, Wendy', 'Evans, David J.']",,,,
,PMC,Infectious Bronchitis Virus E Protein Is Targeted to the Golgi Complex and Directs Release of Virus-Like Particles,,PMC111949,,,"The coronavirus E protein is a poorly characterized small envelope protein present in low levels in virions. We are interested in the role of E in the intracellular targeting of infectious bronchitis virus (IBV) membrane proteins. We generated a cDNA clone of IBV E and antibodies to the E protein to study its cell biological properties in the absence of virus infection. We show that IBV E is an integral membrane protein when expressed in cells from cDNA. Epitope-specific antibodies revealed that the C terminus of IBV E is cytoplasmic and the N terminus is translocated. The short luminal N terminus of IBV E contains a consensus site for N-linked glycosylation, but the site is not used. When expressed using recombinant vaccinia virus, the IBV E protein is released from cells at low levels in sedimentable particles that have a density similar to that of coronavirus virions. The IBV M protein is incorporated into these particles when present. Indirect immunofluorescence microscopy showed that E is localized to the Golgi complex in cells transiently expressing IBV E. When coexpressed with IBV M, both from cDNA and in IBV infection, the two proteins are colocalized in Golgi membranes, near the coronavirus budding site. Thus, even though IBV E is present at low levels in virions, it is apparently expressed at high levels in infected cells near the site of virus assembly.",,"['Corse, Emily', 'Machamer, Carolyn E.']",,,,
,PMC,Frequent Homologous Recombination Events between Molecules of One RNA Component in a  Multipartite RNA Virus,,PMC111936,,,"Brome mosaic bromovirus (BMV), a tripartite plus-sense RNA virus, has been used as a model system to study homologous RNA recombination among molecules of the same RNA component. Pairs of BMV RNA3 variants carrying marker mutations at different locations were coinoculated on a local lesion host, and the progeny RNA3 in a large number of lesions was analyzed. The majority of doubly infected lesions accumulated the RNA3 recombinants. The distribution of the recombinant types was relatively even, indicating that both RNA3 counterparts could serve as donor or as acceptor molecules. The frequency of crossovers between one pair of RNA3 variants, which possessed closely located markers, was similar to that of another pair of RNA3 variants with more distant markers, suggesting the existence of an internal recombination hot spot. The majority of crossovers were precise, but some recombinants had minor sequence modifications, possibly marking the sites of imprecise homologous crossovers. Our results suggest discontinuous RNA replication, with the replicase changing among the homologous RNA templates and generating RNA diversity. This approach can be easily extended to other RNA viruses for identification of homologous recombination hot spots.",,"['Bruyere, A.', 'Wantroba, M.', 'Flasinski, S.', 'Dzianott, A.', 'Bujarski, J. J.']",,,,
,PMC,Subgenomic Negative-Strand RNA Function during Mouse Hepatitis Virus Infection,,PMC111917,,,"Mouse hepatitis virus (MHV)-infected cells contain full-length and subgenomic-length positive- and negative-strand RNAs. The origin and function of the subgenomic negative-strand RNAs is controversial. In this report we demonstrate that the synthesis and molar ratios of subgenomic negative strands are similar in alternative host cells, suggesting that these RNAs function as important mediators of positive-strand synthesis. Using kinetic labeling experiments, we show that the full-length and subgenomic-length replicative form RNAs rapidly accumulate and then saturate with label, suggesting that the subgenomic-length negative strands are the principal mediators of positive-strand synthesis. Using cycloheximide, which preferentially inhibits negative-strand and to a lesser extent positive-strand synthesis, we demonstrate that cycloheximide treatment equally inhibits full-length and subgenomic-length negative-strand synthesis. Importantly, following treatment, previously transcribed negative strands remain in transcriptionally active complexes even in the absence of new negative-strand synthesis. These findings indicate that the subgenomic-length negative strands are the principal templates of positive-strand synthesis during MHV infection.",,"['Baric, Ralph S.', 'Yount, Boyd']",,,,
,PMC,The Viral Nucleocapsid Protein of Transmissible Gastroenteritis Coronavirus (TGEV) Is Cleaved by Caspase-6 and -7  during TGEV-Induced Apoptosis,,PMC111911,,,"The transmissible gastroenteritis coronavirus (TGEV), like many other viruses, exerts much of its cytopathic effect through the induction of apoptosis of its host cell. Apoptosis is coordinated by a family of cysteine proteases, called caspases, that are activated during apoptosis and participate in dismantling the cell by cleaving key structural and regulatory proteins. We have explored the caspase activation events that are initiated upon infection of the human rectal tumor cell line HRT18 with TGEV. We show that TGEV infection results in the activation of caspase-3, -6, -7, -8, and -9 and cleavage of the caspase substrates eIF4GI, gelsolin, and α-fodrin. Surprisingly, the TGEV nucleoprotein (N) underwent proteolysis in parallel with the activation of caspases within the host cell. Cleavage of the N protein was inhibited by cell-permeative caspase inhibitors, suggesting that this viral structural protein is a target for host cell caspases. We show that the TGEV nucleoprotein is a substrate for both caspase-6 and -7, and using site-directed mutagenesis, we have mapped the cleavage site to VVPD(359)↓. These data demonstrate that viral proteins can be targeted for destruction by the host cell death machinery.",,"['Eléouët, Jean-François', 'Slee, Elizabeth A.', 'Saurini, Françoise', 'Castagné, Nathalie', 'Poncet, Didier', 'Garrido, Carmen', 'Solary, Eric', 'Martin, Seamus J.']",,,,
,PMC,Chimeric Matrix Proteins Encoded by Defective Proviruses with Large Internal Deletions in Human T-Cell Leukemia  Virus Type 1-Infected Humans,,PMC111906,,,"Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and other diseases. The mechanisms of virus pathogenesis are still obscure. The occurrence of defective proviruses in HTLV-1-infected cell lines and the peripheral blood mononuclear cells (PBMC) of infected individuals is a frequent feature of virus infection. We detected defective proviruses with large internal deletions in PBMC from ATLL and HAM/TSP patients and in asymptomatic HTLV-1 carriers. Seventeen PCR-amplified defective proviruses were sequenced, and three types of deletions were found. Besides truncated MA and the 5′ end of the genome, truncated CA, truncated SU, and more frequently truncated TM linked to the pX region were detected. Reverse transcription-PCR analysis of PBMC from ATLL patients and asymptomatic carriers also revealed RNA transcripts with large internal deletions. Analysis of two RT-PCR cDNA clones confirmed a Gag-TM-pX structure of the transcripts. Most defective proviruses contained numerous internal stop codons, but some were capable of coding for the truncated MA linked to a variable out-of-frame peptide. Cloned defective proviruses with long open reading frames were subjected to in vitro transcription-translation followed by radioimmunoprecipitation, which showed expression of chimeric proteins between 8 and 12 kDa. Possible roles of defective proviruses and chimeric proteins are discussed, although there is no firm association with pathogenesis.",,"['Morozov, Vladimir A.', 'Lagaye, Sylvie', 'Taylor, Graham P.', 'Matutes, Estella', 'Weiss, Robin A.']",,,,
,PMC,A conserved hairpin structure in Alfamovirus and Bromovirus subgenomic promoters is required for efficient RNA synthesis in vitro.,,PMC1369951,,,"The coat protein gene in RNA 3 of alfalfa mosaic virus (AMV; genus Alfamovirus, family Bromoviridae) is translated from the subgenomic RNA 4. Analysis of the subgenomic promoter (sgp) in minus-strand RNA 3 showed that a sequence of 37 nt upstream of the RNA 4 start site (nt +1) was sufficient for full sgp activity in an in vitro assay with the purified viral RNA-dependent RNA-polymerase (RdRp). The sequence of nt -6 to -29 could be folded into a potential hairpin structure with a loop represented by nt -16, -17, and -18, and a bulge involving nt -23. By introducing mutations that disrupted base pairing and compensatory mutations that restored base pairing, it was shown that base pairing in the top half of the putative stem (between the loop and bulge) was essential for sgp activity, whereas base pairing in the bottom half of the stem was less stringently required. Deletion of the bulged residue A-23 or mutation of this residue into a C strongly reduced sgp activity, but mutation of A-23 into U or G had little effect on sgp activity. Mutation of loop residues A-16 and A-17 affected sgp activity, whereas mutation of U-18 did not. Using RNA templates corresponding to the sgp of brome mosaic virus (BMV; genus Bromovirus, family Bromoviridae) and purified BMV RdRp, evidence was obtained indicating that also in BMV RNA a triloop hairpin structure is required for sgp activity.",,"['Haasnoot, P C', 'Brederode, F T', 'Olsthoorn, R C', 'Bol, J F']",,,,
,PMC,Etiology and evaluation of diarrhea in AIDS: A global perspective at the millennium,http://dx.doi.org/10.3748/wjg.v6.i2.177,PMC4723481,,,,,"Wilcox, C. Mel",,,,
,PMC,Molecular and Functional Analysis of the Human Prothrombinase Gene (HFGL2) and Its Role in Viral Hepatitis,,PMC1876871,,,"In the present studies, we report the cloning and structural characterization of the HFGL2 gene and its functional role in human fulminant hepatitis. The HFGL2 gene is approximately 7 kb in length with 2 exons. The putative promoter contains cis element consensus sequences that strongly suggest the inducibility of its expression. From the nucleotide sequence of the human gene, a 439-amino acid long protein is predicted. The overall identity between the murine fgl2 and hfgl2 coded proteins is over 70%. About 225 amino acids at the carboxyl end of these molecules are almost 90% identical, and correspond to a well-conserved fibrinogen-related domain. Both HFGL2 and FGL2 encode a type II transmembrane protein with a predicted catalytic domain toward the amino terminus of the protein. Transient transfection of Chinese hamster ovary (CHO) cells with a full-length cDNA of HFGL2 coding region resulted in high levels of prothrombinase activity. Livers from 8 patients transplanted for fulminant viral hepatitis were examined for extent of necrosis, inflammation, fibrin deposition, and HFGL2 induction. In situ hybridization showed positive staining of macrophages in areas of active hepatocellular necrosis. Fibrin stained positively in these areas and was confirmed by electron microscopy. These studies define a unique prothrombinase gene (HFGL2) and implicate its importance in the pathogenesis of fulminant viral hepatitis.",,"['Levy, Gary A.', 'Liu, Mingfeng', 'Ding, Jinwen', 'Yuwaraj, Shankary', 'Leibowitz, Julian', 'Marsden, Philip A.', 'Ning, Qin', 'Kovalinka, Ana', 'Phillips, M. James']",,,,
,PMC,Protection studies on winter dysentery caused by bovine coronavirus in cattle using antigens prepared from infected cell lysates.,,PMC1189599,,,"Cells infected with bovine coronavirus (BCV) were solubilized with Triton X-100 to yield a cell lysate (CL) antigen having high hemagglutinating (HA) titers. The antigen gave high HA titers using rat erythrocytes, suggesting that it contained large amounts of hemagglutinin esterase (HE) antigen. The CL antigen, combined with an oil adjuvant, was tested for protective and antibody-inducing activities in cattle. Four groups (2 cattle/group) of cattle were inoculated with CL antigen having HA titers of 16 000, 4000, 1000, and 250. Another group served as untreated controls. Two intramuscular inoculations were given at an interval of 3 wk. The animals were challenged with virus 1 wk after the second inoculation. The groups immunized with the CL antigen having an HA titer of 4000 or 16 000 produced hemagglutination inhibition (HI) antibody titers of > 320 and serum neutralizing (SN) antibody titers of > 1280. These groups of animals showed no clinical abnormalities after challenge. In the groups immunized with CL antigen at an HA titer of 1000 or 250, HI antibody titers were 40 to 160 and SN titers were 80 to 640. The cattle with HI antibody titers of > or = 160 and the SN titers of > or = 640 showed no clinical signs, but the cattle with the HI antibody titer < 80 and the SN antibody titer < 160 developed watery diarrhea and fever after challenge. These results indicate that CL antigen with high HA titer induces antibody production in cattle that provides effective protection against winter dysentery.",,"['Takamura, K', 'Okada, N', 'Ui, S', 'Hirahara, T', 'Shimizu, Y']",,,,
,PMC,"Charged Residues in the Transmembrane Domains of Hepatitis C Virus Glycoproteins Play a Major Role in the Processing, Subcellular Localization, and Assembly of These Envelope Proteins",,PMC111872,,,"For most membrane proteins, the transmembrane domain (TMD) is more than just an anchor to the membrane. The TMDs of hepatitis C virus (HCV) envelope proteins E1 and E2 are extreme examples of the multifunctionality of such membrane-spanning sequences. Indeed, they possess a signal sequence function in their C-terminal half, play a major role in endoplasmic reticulum localization of E1 and E2, and are potentially involved in the assembly of these envelope proteins. These multiple functions are supposed to be essential for the formation of the viral envelope. As for the other viruses of the family Flaviviridae, these anchor domains are composed of two stretches of hydrophobic residues separated by a short segment containing at least one fully conserved charged residue. Replacement of these charged residues by an alanine in HCV envelope proteins led to an alteration of all of the functions performed by their TMDs, indicating that these functions are tightly linked together. These data suggest that the charged residues of the TMDs of HCV glycoproteins play a key role in the formation of the viral envelope.",,"['Cocquerel, Laurence', 'Wychowski, Czeslaw', 'Minner, Frederic', 'Penin, François', 'Dubuisson, Jean']",,,,
,PMC,Four Proteins Processed from the Replicase Gene Polyprotein of Mouse Hepatitis Virus Colocalize in the Cell Periphery and Adjacent to Sites of Virion Assembly,,PMC111839,,,"The replicase gene (gene 1) of the coronavirus mouse hepatitis virus (MHV) encodes two co-amino-terminal polyproteins presumed to incorporate all the virus-encoded proteins necessary for viral RNA synthesis. The polyproteins are cotranslationally processed by viral proteinases into at least 15 mature proteins, including four predicted cleavage products of less than 25 kDa that together would comprise the final 59 kDa of protein translated from open reading frame 1a. Monospecific antibodies directed against the four distinct domains detected proteins of 10, 12, and 15 kDa (p1a-10, p1a-12, and p1a-15) in MHV-A59-infected DBT cells, in addition to a previously identified 22-kDa protein (p1a-22). When infected cells were probed by immunofluorescence laser confocal microscopy, p1a-10, -22, -12, and -15 were detected in discrete foci that were prominent in the perinuclear region but were widely distributed throughout the cytoplasm as well. Dual-labeling experiments demonstrated colocalization of the majority of p1a-22 in replication complexes with the helicase, nucleocapsid, and 3C-like proteinase, as well as with p1a-10, -12, and -15. p1a-22 was also detected in separate foci adjacent to the replication complexes. The majority of complexes containing the gene 1 proteins were distinct from sites of accumulation of the M assembly protein. However, in perinuclear regions the gene 1 proteins and nucleocapsid were intercalated with sites of M protein localization. These results demonstrate that the complexes known to be involved in RNA synthesis contain multiple gene 1 proteins and are closely associated with structural proteins at presumed sites of virion assembly.",,"['Bost, Anne Gibson', 'Carnahan, Robert H.', 'Lu, Xiao Tao', 'Denison, Mark R.']",,,,
,PMC,cis- and trans-Acting Elements in Flavivirus RNA Replication,,PMC111826,,,"Most of the seven flavivirus nonstructural proteins (NS1 to NS5) encoded in the distal two-thirds of the RNA positive-sense genome are believed to be essential components of RNA replication complexes. To explore the functional relationships of these components in RNA replication, we used trans-complementation analysis of full-length infectious RNAs of Kunjin (KUN) virus with a range of lethal in-frame deletions in the nonstructural coding region, using as helper a repBHK cell line stably producing functional replication complexes from KUN replicon RNA. Recently we showed that replication of KUN RNAs with large carboxy-terminal deletions including the entire RNA polymerase region in the NS5 gene, representing 34 to 75% of the NS5 coding content, could be complemented after transfection into repBHK cells. In this study we have demonstrated that KUN RNAs with deletions of 84 to 97% of the NS1 gene, or of 13 to 63% of the NS3 gene including the entire helicase region, were also complemented in repBHK cells with variable efficiencies. In contrast, KUN RNAs with deletions in any of the other four nonstructural genes NS2A, NS2B, NS4A, and NS4B were not complemented. We have also demonstrated successful trans complementation of KUN RNAs containing either combined double deletions in the NS1 and NS5 genes or triple deletions in the NS1, NS3, and NS5 genes comprising as much as 38% of the entire nonstructural coding content. Based on these and our previous complementation results, we have generated a map of cis- and trans-acting elements in RNA replication for the nonstructural coding region of the flavivirus genome. These results are discussed in the context of our model on formation and composition of the flavivirus replication complex, and we suggest molecular mechanisms by which functions of some defective components of the replication complex can be complemented by their wild-type counterparts expressed from another (helper) RNA molecule.",,"['Khromykh, Alexander A.', 'Sedlak, Petra L.', 'Westaway, Edwin G.']",,,,
,PMC,Isolation and Characterization of an Arterivirus Defective Interfering RNA Genome,,PMC111816,,,"Equine arteritis virus (EAV), the type member of the family Arteriviridae, is a single-stranded RNA virus with a positive-stranded genome of approximately 13 kb. EAV uses a discontinuous transcription mechanism to produce a nested set of six subgenomic mRNAs from which its structural genes are expressed. We have generated the first documented arterivirus defective interfering (DI) RNAs by serial undiluted passaging of a wild-type EAV stock in BHK-21 cells. A cDNA copy of the smallest DI RNA (5.6 kb) was cloned. Upon transfection into EAV-infected BHK-21 cells, transcripts derived from this clone (pEDI) were replicated and packaged. Sequencing of pEDI revealed that the DI RNA was composed of three segments of the EAV genome (nucleotides 1 to 1057, 1388 to 1684, and 8530 to 12704) which were fused in frame with respect to the replicase reading frame. Remarkably, this DI RNA has retained all of the sequences encoding the structural proteins. By insertion of the chloramphenicol acetyltransferase reporter gene in the DI RNA genome, we were able to delimitate the sequences required for replication/DI-based transcription and packaging of EAV DI RNAs and to reduce the maximal size of a replication-competent EAV DI RNA to approximately 3 kb.",,"['Molenkamp, Richard', 'Rozier, Babette C. D.', 'Greve, Sophie', 'Spaan, Willy J. M.', 'Snijder, Eric J.']",,,,
,PMC,A Single-Amino-Acid Substitution of a Tyrosine Residue in the Rubella Virus E1 Cytoplasmic Domain Blocks Virus Release,,PMC111801,,,"Rubella virus particles, consisting of a nucleocapsid surrounded by a lipid envelope in which two virus-encoded glycoproteins E1 and E2 are embedded, assemble on intracellular membranes and are secreted from cells, possibly via the cellular secretory pathway. We have recently demonstrated that the cytoplasmic domain of E1 (residues 469 to 481, KCLYYLRGAIAPR) is required for virus release. Alteration of cysteine 470 to alanine did not affect virus release, whereas mutation of leucine 471 to alanine reduced virus production by 90%. In the present study, substitutions of remaining amino acids in the E1 cytoplasmic domain were made in order to investigate the role of each amino acid in regulating rubella virus release. Generated mutants were analyzed in the context of infectious full-length cDNA clone and virus-like particles using combined genetic, biochemical, and electron microscopic approaches. Substitution of a single residue of tyrosine 472 to alanine or tyrosine 473 to serine resulted in a block in virus release without affecting protein transport and virus budding into the lumen of the Golgi complexes. Infectious RNA transcripts bearing these mutations were incapable of forming plaques. Mutants with substitutions at the amino-terminal region (leucine 474, arginine 475, and glycine 476) in the E1 cytoplasmic domain had reduced virus release and small-plaque phenotype, while mutants with substitutions at the carboxy-terminal region (alanine 477, isoleucine 478, alanine 479, proline 480, and arginine 481) had only marginal defects in virus release. Plaque-forming revertants could be isolated from mutants Y472A and Y473S. Sequencing analysis revealed that the substituted serine residue in mutant Y473S reverted to the original tyrosine residue, whereas the substituted alanine residue in mutant Y472A was retained. These results indicate that the E1 cytoplasmic domain modulates virus release in a sequence-dependent manner and that the tyrosine residues are critical for this function. We postulate that residues YYLRG constitute a domain in the E1 tail that may interact with other proteins and this interaction is involved in regulating virus release.",,"['Yao, Jiansheng', 'Gillam, Shirley']",,,,
,PMC,"Development, Characterization, and Diagnostic Applications of Monoclonal Antibodies against Bovine Rotavirus",,PMC95862,,,"Hybridomas secreting monoclonal antibodies (MAbs) against the Nebraska calf diarrhea strain of bovine rotavirus (BRV) were characterized. Indirect fluorescent-antibody assay, immunodot assay, and immunoprecipitation were used to select hybridomas that produced anti-BRV MAbs. Seven of the MAbs were shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot assay to be reactive with the BRV outer capsid protein, VP7, which has a molecular mass of 37.5 kDa. None of the seven MAbs were reactive with canine rotavirus, bovine coronavirus, or uninfected Madin-Darby bovine kidney cells. Two clones, 8B4 (immunoglobulin G2a [IgG2a]) and 2B11 (IgG1), were found suitable for use in an antigen capture enzyme-linked immunosorbent assay for detecting BRV in bovine fecal samples. Both were subtype A specific (G6 subtype) but did not react with all isolates of BRV group A.",,"['Al-Yousif, Yousif', 'Al-Majhdi, Fahad', 'Chard-Bergstrom, Cindy', 'Anderson, Joe', 'Kapil, Sanjay']",,,,
,PMC,Cocaine Causes Increased Type I Interferon Secretion by both L929 Cells and Murine Macrophages,,PMC95856,,,"Cocaine has been demonstrated to have a number of different effects on immune cell functions. We have reported alterations of cellular functions by macrophages (Mφ) exposed to cocaine in vitro, including the inhibition of mouse hepatitis virus replication. Here, we present evidence that cocaine stimulates the secretion of an antiviral product that is neutralized by anti-interferon (anti-IFN). A dose-dependent increase in the secretion of IFN by both Mφ and L929 cells incubated with cocaine, with a concomitant decrease in virus replication, is also reported. The increase in IFN secretion was most pronounced when cells were cultured in the presence of the IFN inducer poly(I·C). The effect of cocaine on IFN production was found to be primarily at the transcript level in both Mφ and L929 cells. These findings further support our previous research demonstrating an antiviral activity of cocaine in vitro. The relevance of this activity to viral infections in general remains to be determined.",,"['Grattendick, K.', 'Jansen, D. B.', 'Lefkowitz, D. L.', 'Lefkowitz, S. S.']",,,,
,PMC,Diagnostic and Public Health Dilemma of Lactose-Fermenting Salmonella enterica Serotype Typhimurium in Cattle  in the Northeastern United States,,PMC86381,,,The presence of lactose-fermenting Salmonella strains in clinical case materials presented to microbiology laboratories presents problems in detection and identification. Failure to detect these strains also presents a public health problem. The laboratory methods used in detecting lactose-fermenting Salmonella enterica serotype Typhimurium from six outbreaks of salmonellosis in veal calves are described. Each outbreak was caused by a multiply-resistant and lactose-fermenting strain of S. enterica serotype Typhimurium. The use of Levine eosin-methylene blue agar in combination with screening of suspect colonies for C8 esterase enzyme and inoculation of colonies into sulfide-indole-motility medium for hydrogen sulfide production was particularly effective for their detection. A hypothesis for the creation of lactose-fermenting salmonellae in the environment is presented. It is proposed that the environment and husbandry practices of veal-raising barns provide a unique niche in which lactose-fermenting salmonellae may arise.,,"['McDonough, Patrick L.', 'Shin, Sang J.', 'Lein, Donald H.']",,,,
,PMC,Contributions of Fas-Fas Ligand Interactions to the Pathogenesis  of Mouse Hepatitis Virus in the Central Nervous System,,PMC111729,,,"The pathogenesis of the neurotropic strain of mouse hepatitis virus in Fas-deficient mice suggested that Fas-mediated cytotoxicity may be required during viral clearance after the loss of perforin-mediated cytotoxicity. The absence of both Fas- and perforin-mediated cytolysis resulted in an uncontrolled infection, suggesting a redundancy of cytolytic pathways to control virus replication.",,"['Parra, Beatriz', 'Lin, Mark T.', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Atkinson, Roscoe', 'Hinton, David R.']",,,,
,PMC,Characterization of the Coronavirus Mouse Hepatitis Virus Strain A59 Small Membrane Protein E,,PMC111715,,,"The small envelope (E) protein has recently been shown to play an essential role in the assembly of coronaviruses. Expression studies revealed that for formation of the viral envelope, actually only the E protein and the membrane (M) protein are required. Since little is known about this generally low-abundance virion component, we have characterized the E protein of mouse hepatitis virus strain A59 (MHV-A59), an 83-residue polypeptide. Using an antiserum to the hydrophilic carboxy terminus of this otherwise hydrophobic protein, we found that the E protein was synthesized in infected cells with similar kinetics as the other viral structural proteins. The protein appeared to be quite stable both during infection and when expressed individually using a vaccinia virus expression system. Consistent with the lack of a predicted cleavage site, the protein was found to become integrated in membranes without involvement of a cleaved signal peptide, nor were any other modifications of the polypeptide observed. Immunofluorescence analysis of cells expressing the E protein demonstrated that the hydrophilic tail is exposed on the cytoplasmic side. Accordingly, this domain of the protein could not be detected on the outside of virions but appeared to be inside, where it was protected from proteolytic degradation. The results lead to a topological model in which the polypeptide is buried within the membrane, spanning the lipid bilayer once, possibly twice, and exposing only its carboxy-terminal domain. Finally, electron microscopic studies demonstrated that expression of the E protein in cells induced the formation of characteristic membrane structures also observed in MHV-A59-infected cells, apparently consisting of masses of tubular, smooth, convoluted membranes. As judged by their colabeling with antibodies to E and to Rab-1, a marker for the intermediate compartment and endoplasmic reticulum, the E protein accumulates in and induces curvature into these pre-Golgi membranes where coronaviruses have been shown earlier to assemble by budding.",,"['Raamsman, Martin J. B.', 'Locker, Jacomine Krijnse', 'de Hooge, Alphons', 'de Vries, Antoine A. F.', 'Griffiths, Gareth', 'Vennema, Harry', 'Rottier, Peter J. M.']",,,,
,PMC,Contribution of the intercalated adenosine at the helical junction to the stability of the gag-pro frameshifting pseudoknot from mouse mammary tumor virus.,,PMC1369923,,,"The mouse mammary tumor virus (MMTV) gag-pro frameshifting pseudoknot is an H-type RNA pseudoknot that contains an unpaired adenosine (A14) at the junction of the two helical stems required for efficient frameshifting activity. The thermodynamics of folding of the MMTV vpk pseudoknot have been compared with a structurally homologous mutant RNA containing a G x U to G-C substitution at the helical junction (U13C RNA), and an A14 deletion mutation in that context (U13CdeltaA14 RNA). Dual wavelength optical melting and differential scanning calorimetry reveal that the unpaired adenosine contributes 0.7 (+/-0.2) kcal mol(-1) at low salt and 1.4 (+/-0.2) kcal mol(-1) to the stability (deltaG(0)37) at 1 M NaCl. This stability increment derives from a favorable enthalpy contribution to the stability deltadeltaH = 6.6 (+/-2.1) kcal mol(-1) with deltadeltaG(0)37 comparable to that predicted for the stacking of a dangling 3' unpaired adenosine on a G-C or G x U base pair. Group 1A monovalent ions, NH4+, Mg2+, and Co(NH3)6(3+) ions stabilize the A14 and deltaA14 pseudoknots to largely identical extents, revealing that the observed differences in stability in these molecules do not derive from a differential or specific accumulation of ions in the A14 versus deltaA14 pseudoknots. Knowledge of this free energy contribution may facilitate the prediction of RNA pseudoknot formation from primary nucleotide sequence (Gultyaev et al., 1999, RNA 5:609-617).",,"['Theimer, C A', 'Giedroc, D P']",,,,
,PMC,RNA motifs mediating in vivo site-specific nonhomologous recombination in (+) RNA virus enforce in vitro nonhomologous crossovers with HIV-1 reverse transcriptase.,,PMC1369917,,,"There are several lines of evidence that both RNA viruses and retroviruses recombine according to a copy choice mechanism. Using the brome mosaic virus (BMV)-based system, we recognized elements in the RNA structure that enhance nonhomologous crossovers within or near the local heteroduplex formed by recombining molecules. The same structural motifs were employed in vitro to test the ability of human immunodeficiency virus reverse transcriptase (HIV-RT) to switch templates during DNA synthesis. We demonstrated that a specific combination of the local double-stranded region with short homologous sequences and a hairpin structure allows template switching by HIV-RT. In contrast to BMV replicase, HIV-RT does not mediate the detectable level of recombination using only the heteroduplex structure, though local hybridization between RNA molecules efficiently pauses primer extension. Moreover, the presented data suggest that a proper arrangement of identified structural motifs can ensure site specificity of RNA-RNA recombination. These results indicate that HIV-RT utilizes the same or a very similar mechanism as BMV replicase to change nonhomologous RNA templates in a site-specific manner.",,"['Figlerowicz, M', 'Bibiłło, A']",,,,
,PMC,"Measles Virus Spread between Neurons Requires Cell Contact but Not CD46 Expression, Syncytium Formation, or Extracellular Virus Production",,PMC111669,,,"In patients with subacute sclerosing panencephalitis (SSPE), which is associated with persistent measles virus (MV) infection in the brain, little infectious virus can be recovered despite the presence of viral RNA and protein. Based on studies of brain tissue from SSPE patients and our work with MV-infected NSE-CD46(+) mice, which express the measles receptor CD46 on neurons, several lines of evidence suggest that the mechanism of viral spread in the central nervous system differs from that in nonneuronal cells. To examine this alternate mechanism of viral spread, as well as the basis for the loss of normal transmission mechanisms, infection and spread of MV Edmonston was evaluated in primary CD46(+) neurons from transgenic mice and differentiated human NT2 neurons. As expected, unlike that between fibroblasts, viral spread between neurons occurred in the absence of syncytium formation and with minimal extracellular virus. Electron microscopy analysis showed that viral budding did not occur from the neuronal surface, although nucleocapsids were present in the cytoplasm and aligned at the cell membrane. We observed many examples of nucleocapsids present in the neuronal processes and aligned at presynaptic neuronal membranes. Cocultures of CD46(+) and CD46(−) neurons showed that cell contact but not CD46 expression is required for MV spread between neurons. Collectively, these results suggest that the neuronal environment prevents the normal mechanisms of MV spread between neurons at the level of viral assembly but allows an alternate, CD46-independent mechanism of viral transmission, possibly through the synapse.",,"['Lawrence, Diane M. P.', 'Patterson, Catherine E.', 'Gales, Tracy L.', ""D'Orazio, Joseph L."", 'Vaughn, Melinda M.', 'Rall, Glenn F.']",,,,
,PMC,Identification of a Novel Cleavage Activity of the First Papain-Like  Proteinase Domain Encoded by Open Reading Frame 1a of the Coronavirus Avian Infectious Bronchitis Virus and Characterization of the Cleavage Products,,PMC111642,,,"The coronavirus Avian infectious bronchitis virus (IBV) employs polyprotein processing as a strategy to express its gene products. Previously we identified the first cleavage event as proteolysis at the Gly(673)-Gly(674) dipeptide bond mediated by the first papain-like proteinase domain (PLPD-1) to release an 87-kDa mature protein. In this report, we demonstrate a novel cleavage activity of PLPD-1. Expression, deletion, and mutagenesis studies showed that the product encoded between nucleotides 2548 and 8865 was further cleaved by PLPD-1 at the Gly(2265)-Gly(2266) dipeptide bond to release an N-terminal 195-kDa and a C-terminal 41-kDa cleavage product. Characterization of the cleavage activity revealed that the proteinase is active on this scissile bond when expressed in vitro in rabbit reticulocyte lysates and can act on the same substrate in trans when expressed in intact cells. Both the N- and C-terminal cleavage products were detected in virus-infected cells and were found to be physically associated. Glycosidase digestion and site-directed mutagenesis studies of the 41-kDa protein demonstrated that it is modified by N-linked glycosylation at the Asn(2313) residue encoded by nucleotides 7465 to 7467. By using a region-specific antiserum raised against the IBV sequence encoded by nucleotides 8865 to 9786, we also demonstrated that a 33-kDa protein, representing the 3C-like proteinase (3CLP), was specifically immunoprecipitated from the virus-infected cells. Site-directed mutagenesis and expression studies showed that a previously predicted cleavage site (Q(2583)-G(2584)) located within the 41-kDa protein-encoding region was not utilized by 3CLP, supporting the conclusion that the 41-kDa protein is a mature viral product.",,"['Lim, K. P.', 'Ng, Lisa F. P.', 'Liu, D. X.']",,,,
,PMC,Biochemical Consequences of a Mutation That Controls the Cholesterol Dependence of Semliki Forest Virus Fusion,,PMC111636,,,"The enveloped alphavirus Semliki Forest virus (SFV) infects cells via a low-pH-triggered membrane fusion reaction that requires cholesterol and sphingolipid in the target membrane. Cholesterol-depleted insect cells are highly resistant to alphavirus infection and were used to select srf-3, an SFV mutant that is ∼100-fold less cholesterol dependent for infection due to a single amino acid change in the E1 spike subunit, proline 226 to serine. Sensitive lipid-mixing assays here demonstrated that the in vitro fusion of srf-3 and wild-type (wt) virus with cholesterol-containing liposomes had comparable kinetics, activation energies, and sphingolipid dependence. In contrast, srf-3 fusion with sterol-free liposomes was significantly more efficient than that of wt virus. Thus, the srf-3 mutation does not affect its general fusion properties with purified lipid bilayers but causes a marked and specific reduction in cholesterol dependence. Upon exposure to low pH, the E1 spike subunit undergoes distinct conformational changes, resulting in the exposure of an acid conformation-specific epitope and formation of an E1 homotrimer. These conformational changes were strongly cholesterol and sphingolipid dependent for wt SFV and strikingly less cholesterol dependent for srf-3. Our results thus demonstrate the functional importance of fusogenic E1 conformational changes in the control of SFV cholesterol dependence.",,"['Chatterjee, Prodyot K.', 'Vashishtha, Malini', 'Kielian, Margaret']",,,,
,PMC,Assembly of Spikes into Coronavirus Particles Is Mediated by the Carboxy-Terminal Domain of the Spike Protein,,PMC111495,,,"The type I glycoprotein S of coronavirus, trimers of which constitute the typical viral spikes, is assembled into virions through noncovalent interactions with the M protein. Here we demonstrate that incorporation is mediated by the short carboxy-terminal segment comprising the transmembrane and endodomain. To this aim, we used the virus-like particle (VLP) system that we developed earlier for the mouse hepatitis virus strain A59 (MHV-A59) and which we describe now also for the unrelated coronavirus feline infectious peritonitis virus (FIPV; strain 79-1146). Two chimeric MHV-FIPV S proteins were constructed, consisting of the ectodomain of the one virus and the transmembrane and endodomain of the other. These proteins were tested for their incorporation into VLPs of either species. They were found to assemble only into viral particles of the species from which their carboxy-terminal domain originated. Thus, the 64-terminal-residue sequence suffices to draw the 1308 (MHV)- or 1433 (FIPV)-amino-acid-long mature S protein into VLPs. Both chimeric S proteins appeared to cause cell fusion when expressed individually, suggesting that they were biologically fully active. This was indeed confirmed by incorporating one of the proteins into virions which thereby acquired a new host cell tropism, as will be reported elsewhere.",,"['Godeke, Gert-Jan', 'de Haan, Cornelis A. M.', 'Rossen, John W. A.', 'Vennema, Harry', 'Rottier, Peter J. M.']",,,,
,PMC,A Central Role for CD4(+) T Cells and RANTES in Virus-Induced Central Nervous System Inflammation and Demyelination,,PMC111476,,,"Infection of C57BL/6 mice with mouse hepatitis virus (MHV) results in a demyelinating encephalomyelitis characterized by mononuclear cell infiltration and white matter destruction similar to the pathology of the human demyelinating disease multiple sclerosis. The contributions of CD4(+) and CD8(+) T cells in the pathogenesis of the disease were investigated. Significantly less severe inflammation and demyelination were observed in CD4(−/−) mice than in CD8(−/−) and C57BL/6 mice (P ≤ 0.002 and P ≤ 0.001, respectively). Immunophenotyping of central nervous system (CNS) infiltrates revealed that CD4(−/−) mice had a significant reduction in numbers of activated macrophages/microglial cells in the brain compared to the numbers in CD8(−/−) and C57BL/6 mice, indicating a role for these cells in myelin destruction. Furthermore, CD4(−/−) mice displayed lower levels of RANTES (a C-C chemokine) mRNA transcripts and protein, suggesting a role for this molecule in the pathogenesis of MHV-induced neurologic disease. Administration of RANTES antisera to MHV-infected C57BL/6 mice resulted in a significant reduction in macrophage infiltration and demyelination (P ≤ 0.001) compared to those in control mice. These data indicate that CD4(+) T cells have a pivotal role in accelerating CNS inflammation and demyelination within infected mice, possibly by regulating RANTES expression, which in turn coordinates the trafficking of macrophages into the CNS, leading to myelin destruction.",,"['Lane, Thomas E.', 'Liu, Michael T.', 'Chen, Benjamin P.', 'Asensio, Valérie C.', 'Samawi, Roger M.', 'Paoletti, Alyssa D.', 'Campbell, Iain L.', 'Kunkel, Stephen L.', 'Fox, Howard S.', 'Buchmeier, Michael J.']",,,,
,PMC,Retargeting of Coronavirus by Substitution of the Spike Glycoprotein Ectodomain: Crossing the Host Cell Species Barrier,,PMC111474,,,"Coronaviruses generally have a narrow host range, infecting one or just a few species. Using targeted RNA recombination, we constructed a mutant of the coronavirus mouse hepatitis virus (MHV) in which the ectodomain of the spike glycoprotein (S) was replaced with the highly divergent ectodomain of the S protein of feline infectious peritonitis virus. The resulting chimeric virus, designated fMHV, acquired the ability to infect feline cells and simultaneously lost the ability to infect murine cells in tissue culture. This reciprocal switch of species specificity strongly supports the notion that coronavirus host cell range is determined primarily at the level of interactions between the S protein and the virus receptor. The isolation of fMHV allowed the localization of the region responsible for S protein incorporation into virions to the carboxy-terminal 64 of the 1,324 residues of this protein. This establishes a basis for further definition of elements involved in virion assembly. In addition, fMHV is potentially the ideal recipient virus for carrying out reverse genetics of MHV by targeted RNA recombination, since it presents the possibility of selecting recombinants, no matter how defective, that have regained the ability to replicate in murine cells.",,"['Kuo, Lili', 'Godeke, Gert-Jan', 'Raamsman, Martin J. B.', 'Masters, Paul S.', 'Rottier, Peter J. M.']",,,,
,PMC,Kinetics of Ribosomal Pausing during Programmed −1 Translational Frameshifting,,PMC85227,,,"In the Saccharomyces cerevisiae double-stranded RNA virus, programmed −1 ribosomal frameshifting is responsible for translation of the second open reading frame of the essential viral RNA. A typical slippery site and downstream pseudoknot are necessary for this frameshifting event, and previous work has demonstrated that ribosomes pause over the slippery site. The translational intermediate associated with a ribosome paused at this position is detected, and, using in vitro translation and quantitative heelprinting, the rates of synthesis, the ribosomal pause time, the proportion of ribosomes paused at the slippery site, and the fraction of paused ribosomes that frameshift are estimated. About 10% of ribosomes pause at the slippery site in vitro, and some 60% of these continue in the −1 frame. Ribosomes that continue in the −1 frame pause about 10 times longer than it takes to complete a peptide bond in vitro. Altering the rate of translational initiation alters the rate of frameshifting in vivo. Our in vitro and in vivo experiments can best be interpreted to mean that there are three methods by which ribosomes pass the frameshift site, only one of which results in frameshifting.",,"['Lopinski, John D.', 'Dinman, Jonathan D.', 'Bruenn, Jeremy A.']",,,,
,PMC,"Associations between ambient ozone, hydrocarbons, and childhood wheezy episodes: a prospective observational study in south east London",http://dx.doi.org/10.1136/oem.57.2.86,PMC1739904,,,"OBJECTIVES—To explore the hypothesis that hydrocarbon species and other air pollutants which accumulate at low and high concentrations of ozone are more directly associated with childhood wheezy episodes than ozone.
METHODS—Prospective observational study over 1 year set in the Lewisham district of south east London. The daily attendance rate of children with acute wheeze at the accident and emergency department of Lewisham Hospital was related to local measurements of ozone, hydrocarbon species, nitrogen dioxide (NO(2)), sulphur dioxide (SO(2)) and small particulate matter with diameter <10µm (PM(10)).
RESULTS—An inverse relation was found between the air pollutants and ozone. After seasonal and meteorological adjustment a non-linear U shaped trend was found between incidence of wheeze and ozone. The trend was significant in children <2 years of age but not in older children. In the younger age group, after adjustment for season, temperature, wind speed, and respiratory infection, the incidence relative to that at the mean daily ozone concentration of 32.7 µg/m(3), was estimated to increase by 65% (95% confidence interval (95% CI) 22% to 122%) at an ozone concentration of 5 µg/m(3) (1.5 SDs below the mean) and by 63% (95%CI −6% to 184%) at 80( )µg/m(3) (2.5 SDs above the mean). For several hydrocarbons there were significant positive linear relations found, again in children <2 years of age but not older children. For benzene, the incidence increased by 8% (95% CI 2 to 13%) per SD (SD 2.8 µg/m(3)) increase in benzene concentration. A same day association between incidence and ozone was found to be the most significant but for other pollutants a lag of 2 days gave the most significant associations. No significant association was found for the non-hydrocarbon pollutants including SO(2), NO(2), and PM(10).
CONCLUSIONS—A U shaped relation was found between ozone and the incidence of wheezy episodes in young children. Certain hydrocarbon pollutants accumulate in the atmosphere when ozone concentrations are low, and are associated with childhood wheezy episodes. However, the U shaped association of ozone on incidence cannot be explained by these other pollutants. The finding supports an earlier finding that incidences of wheeze are at a minimum when ozone concentrations are 30-40 µg/m(3).


Keywords: air pollution; ozone; hydrocarbons; childhood wheezing",,"['Buchdahl, R.', 'Willems, C. D.', 'Vander, M.', 'Babiker, A.']",,,,
,PMC,Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations,http://dx.doi.org/10.1136/thorax.55.2.114,PMC1745686,,,"BACKGROUND—Although it is presumed that exacerbations of chronic obstructive pulmonary disease (COPD) are associated with increased airway inflammation, there is little information available on inflammatory markers during an exacerbation and the relationship with severity or time course of recovery. A study was undertaken to investigate the sputum cell and cytokine characteristics of COPD when stable and during an exacerbation.
METHODS—Induced sputum samples from 57 patients with moderate to severe COPD were analysed (44 samples were taken during a stable period and 37 during an exacerbation). The patients recorded daily symptoms on diary cards. Cell counts and sputum levels of interleukin (IL)-6 and IL-8 were measured.
RESULTS—Patients with ⩾3 exacerbations/year had higher median stable sputum levels of IL-6 (110 (95% CI 11 to 215) pg/ml) and IL-8 (6694 (95% CI 3120 to 11995) pg/ml) than those with ⩽2 exacerbations/year (22 (95% CI 12 to 93) and 1628 (95% CI 607 to 4812) pg/ml, respectively). Median IL-6 levels were increased during exacerbations compared with stable conditions. The levels of IL-6 during exacerbations were related to the presence of a cold and to the total cell count and eosinophil and lymphocyte numbers, while IL-8 was positively correlated with all sputum cell counts. Sputum cell counts and cytokine levels during an exacerbation did not predict the size and duration of lung function changes in the exacerbation.
CONCLUSIONS—Patients with more frequent exacerbations have higher baseline sputum cytokine levels, which may predict the frequency of future exacerbations.",,"['Bhowmik, A.', 'Seemungal, T.', 'Sapsford, R.', 'Wedzicha, J.']",,,,
,PMC,Bovine respiratory disease: commercial vaccines currently available in Canada.,,PMC1476343,,,"Bovine respiratory disease (BRD) remains a significant cost to both the beef and dairy industries. In the United States, an estimated 640 million dollars is lost annually due to BRD. Losses are largely a result of pneumonic pasteurellosis (""shipping fever""), enzootic pneumonia of calves, and atypical interstitial pneumonia. In Canada, over 80% of the biologics licensed for use in cattle are against agents associated with BRD. The objectives of this paper were (a) to summarize information available concerning commercial vaccines currently used in Canada for protection against BRD, and (b) to provide an easily accessible resource for veterinary practitioners and researchers. Information from the most recent Compendium of Veterinary Products has been tabulated for each vaccine by trade name, according to vaccine type, and the pathogens against which they are designed to protect. Additional information from published articles (peer-reviewed and other) has been provided and referenced.",,"['Bowland, S L', 'Shewen, P E']",,,,
,PMC,Characterization of a Monoclonal Antibody and Its  Single-Chain Antibody Fragment Recognizing the Nucleoside  Triphosphatase/Helicase Domain of the Hepatitis C Virus Nonstructural 3 Protein,,PMC95823,,,"We have produced a murine monoclonal antibody (MAb), ZX10, recognizing the NTPase/helicase domain of the hepatitis C virus (HCV) nonstructural 3 protein (NS3), from which we designed a single-chain variable fragment (ScFv). The ZX10 MAb recognized a discontinuous epitope of the NTPase/helicase domain, of which the linear sequence GEIPFYGKAIPL at residues 1371 to 1382 constitutes one part. cDNAs from variable regions coding for the heavy and light chains were cloned, sequenced, and assembled into the NS3-ScFv, which was inserted into procaryotic and eucaryotic expression vectors. Escherichia coli-expressed NS3-ScFv inhibited the binding of the ZX10 MAb to NS3, confirming a retained specificity. However, the ability to bind the peptide 1371–1382 had been lost. In vitro-translated NS3-ScFv and HCV NS3/NS4A were coprecipitated by antibodies to HCV NS4A, confirming the in vitro activity of the NS3 ScFv. Thus, we have designed a functional NS3 NTPase/helicase domain-specific ScFv which should be evaluated further with respect to disturbing enzymatic functions of the NS3 protein.",,"['Zhang, Zhu-Xu', 'Lazdina, Una', 'Chen, Margaret', 'Peterson, Darrell L.', 'Sällberg, Matti']",,,,
,PMC,"VP7 and VP4 Genotyping of Human Group A Rotavirus in Buenos Aires, Argentina",,PMC88704,,,"Specific and sensitive tests for the detection and typing of group A rotavirus strains are needed for a more comprehensive knowledge of the epidemiology of rotaviral infection. In this study 500 stool specimens taken from 1996 to 1998 from children with acute diarrhea in Buenos Aires were examined. Group A rotavirus was unequivocally demonstrated in 62% of the samples tested by enzyme-linked immunosorbent assay (ELISA) for detection of VP6 antigen, polyacrylamide gel electrophoresis of double-stranded RNA, and reverse transcription-PCR (RT-PCR) for amplification of the VP7:G (1,062 bp) and VP4:P (876 bp) genes. Only five positive specimens were found by RT-PCR but not by ELISA. G and P typing was carried out by nested amplification of variable sequences of the VP7 and the VP4 genes with six G- and five P-type-specific primers (multiplex PCR). Results obtained by this method showed the prevalence of the following G and P types: G1, 39%; G2, 43%; G4, 4%; P[8], 16%; P[4], 71%. Unexpectedly, the G-P type combination most frequently found was G2P[4] (43%) rather than G1P[8] (12%), which is the most commonly found worldwide. Unusual strains of the type G1P[4] accounted for 14% of the total, while mixed infections with more than one type were found in 10% of the samples. Detection of fecal rotavirus-specific immunoglobulin M (IgM) and IgA antibodies in consecutive samples of two patients taken at daily intervals demonstrated that high levels of IgM and IgA antibodies were detected on day 1 after the onset of disease and that the samples remained positive for about 10 days, after which virus shedding was no longer observed. Multiplex PCR offers a sensitive and specific alternative to determine the prevalence of group A rotavirus G and P types and to identify the emergence of uncommon strains, whereas detection of fecal IgM and IgA antibodies represents a useful supplement to virus detection for the diagnosis of current or recently acquired infections.",,"['Argüelles, M. H.', 'Villegas, G. A.', 'Castello, A.', 'Abrami, A.', 'Ghiringhelli, P. D.', 'Semorile, L.', 'Glikmann, G.']",,,,
,PMC,Pseudorabies Virus Expressing Bovine Herpesvirus 1 Glycoprotein B Exhibits Altered Neurotropism  and Increased Neurovirulence,,PMC111602,,,"Herpesvirus glycoproteins play dominant roles in the initiation of infection of target cells in culture and thus may also influence viral tropism in vivo. Whereas the relative contribution of several nonessential glycoproteins to neurovirulence and neurotropism of Pseudorabies virus (PrV), an alphaherpesvirus which causes Aujeszky's disease in pigs, has recently been uncovered in studies using viral deletion mutants, the importance of essential glycoproteins is more difficult to assess. We isolated an infectious PrV mutant, PrV-9112C2, which lacks the gene encoding the essential PrV glycoprotein B (gB) but stably carries in its genome and expresses the homologous gene of bovine herpesvirus 1 (BHV-1) (A. Kopp and T. C. Mettenleiter, J. Virol. 66:2754–2762, 1992). Apart from exhibiting a slight delay in penetration kinetics, PrV-9112C2 was similar in its growth characteristics in cell culture to wild-type PrV. To analyze the effect of the exchange of these homologous glycoproteins in PrV's natural host, swine, 4-week-old piglets were intranasally infected with 10(6) PFU of either wild-type PrV strain Kaplan (PrV-Ka), PrV-9112C2, or PrV-9112C2R, in which the PrV gB gene was reinserted instead of the BHV-1 gB gene. Animals infected with PrV-Ka and PrV-9112C2R showed a similar course of disease, i.e., high fever, marked respiratory symptoms but minimal neurological disorders, and excretion of high amounts of virus. All animals survived the infection. In contrast, animals infected with PrV-9112C2 showed no respiratory symptoms and developed only mild fever. However, on day 5 after infection, all piglets developed severe central nervous system (CNS) symptoms leading to death within 48 to 72 h. Detailed histological analyses showed that PrV-9112C2R infected all regions of the nasal mucosa and subsequently spread to the CNS preferentially by the trigeminal route. In contrast, PrV-9112C2 primarily infected the olfactory epithelium and spread via the olfactory route. In the CNS, more viral antigen and significantly more pronounced histological changes resulting in more severe encephalitis were found after PrV-9112C2 infection. Thus, our results demonstrate that replacement of PrV gB by the homologous BHV-1 glycoprotein resulted in a dramatic increase in neurovirulence combined with an alteration in the route of neuroinvasion, indicating that the essential gB is involved in determining neurotropism and neurovirulence of PrV.",,"['Gerdts, Volker', 'Beyer, Jörg', 'Lomniczi, Béla', 'Mettenleiter, Thomas C.']",,,,
,PMC,Identification of a Bovine Coronavirus Packaging Signal,,PMC111575,,,"A region of the bovine coronavirus (BCV) genome that functions as a packaging signal has been cloned. The 291-nucleotide clone shares 72% homology with the region of mouse hepatitis coronavirus (MHV) gene 1b that contains the packaging signal. RNA transcripts were packaged into both BCV and MHV virions when the cloned region was appended to a noncoronavirus RNA. This is the first identification of a BCV packaging signal. The data demonstrate that the BCV genome contains a sequence that is conserved at both the sequence and functional levels, thus broadening our insight into coronavirus packaging.",,"['Cologna, Raymond', 'Hogue, Brenda G.']",,,,
,PMC,The CEACAM1-L Glycoprotein Associates with the Actin Cytoskeleton and Localizes to Cell–Cell Contact through Activation of Rho-like GTPases,,PMC14757,,,"Associations between plasma membrane-linked proteins and the actin cytoskeleton play a crucial role in defining cell shape and determination, ensuring cell motility and facilitating cell–cell or cell–substratum adhesion. Here, we present evidence that CEACAM1-L, a cell adhesion molecule of the carcinoembryonic antigen family, is associated with the actin cytoskeleton. We have delineated the regions involved in actin cytoskeleton association to the distal end of the CEACAM1-L long cytoplasmic domain. We have demonstrated that CEACAM1-S, an isoform of CEACAM1 with a truncated cytoplasmic domain, does not interact with the actin cytoskeleton. In addition, a major difference in subcellular localization of the two CEACAM1 isoforms was observed. Furthermore, we have established that the localization of CEACAM1-L at cell–cell boundaries is regulated by the Rho family of GTPases. The retention of the protein at the sites of intercellular contacts critically depends on homophilic CEACAM1–CEACAM1 interactions and association with the actin cytoskeleton. Our results provide new evidence on how the Rho family of GTPases can control cell adhesion: by directing an adhesion molecule to its proper cellular destination. In addition, these results provide an insight into the mechanisms of why CEACAM1-L, but not CEACAM1-S, functions as a tumor cell growth inhibitor.",,"['Sadekova, Svetlana', 'Lamarche-Vane, Nathalie', 'Li, Xiaodong', 'Beauchemin, Nicole']",,,,
,PMC,Efficient Export of the Vesicular Stomatitis Virus G Protein from the Endoplasmic Reticulum Requires a Signal in the Cytoplasmic Tail That Includes Both Tyrosine-based and Di-acidic Motifs,,PMC14753,,,"The vesicular stomatitis virus (VSV) G protein is a model transmembrane glycoprotein that has been extensively used to study the exocytotic pathway. A signal in the cytoplasmic tail of VSV G (DxE or Asp-x-Glu, where x is any amino acid) was recently proposed to mediate efficient export of the protein from the endoplasmic reticulum (ER). In this study, we show that the DxE motif only partially accounts for efficient ER exit of VSV G. We have identified a six-amino-acid signal, which includes the previously identified Asp and Glu residues, that is required for efficient exit of VSV G from the ER. This six-residue signal also includes the targeting sequence YxxØ (where x is any amino acid and Ø is a bulky, hydrophobic residue) implicated in several different sorting pathways. The only defect in VSV G proteins with mutations in the six-residue signal is slow exit from the ER; folding and oligomerization in the ER are normal, and the mutants eventually reach the plasma membrane. Addition of this six-residue motif to an inefficiently transported reporter protein is sufficient to confer an enhanced ER export rate. The signal we have identified is highly conserved among divergent VSV G proteins, and we suggest this reflects the importance of this motif in the evolution of VSV G as a proficient exocytic protein.",,"['Sevier, Carolyn S.', 'Weisz, Ora A.', 'Davis, Mollie', 'Machamer, Carolyn E.']",,,,
,PMC,Biologic functions of the IFN-γ receptors,,PMC4154595,,,"Interferon-gamma (IFN-γ) is a cytokine that plays an important role in inducing and modulating an array of immune responses. Cellular responses to IFN-γ are mediated by its heterodimeric cell-surface receptor (IFN-γR), which activates downstream signal transduction cascades, ultimately leading to the regulation of gene expression. In order to study the role of IFN-γ in a number of immune responses and pathways, researchers have generated mice with altered patterns of IFN-γR gene expression. These studies, together with analyses of naturally occurring mutations of the IFN-γR in man, have been instrumental in elucidating the diverse functions of IFN-γ, and are the subject of this review.",,"['Tau, G.', 'Rothman, P.']",,,,
,PMC,Multiplex PCR for Detection and Typing of Porcine Circoviruses,,PMC85845,,,"Sets of oligonucleotide primers were designed according to the sequences of the open reading frames (ORFs) ORF1 and ORF2 of the prototype nonpathogenic PK-15 strain of porcine circovirus (PCV) type 1 (PCV-1). By the PCR performed with the various primer sets, genomic DNA or RNA from other bacterial or viral pathogens of the respiratory tracts of pigs could not be amplified. A positive amplification reaction could be visualized with DNA extracted from a viral suspension containing as few as 10 viral particles per ml. No DNA fragment could be amplified from lysates of continuous porcine cell lines (PT, ST, and PFT cells) known to be negative for PCV. When tested with clinical samples from pigs, the results of the single PCR method showed nearly 93% (13 of 14 samples) correlation with histopathological and immunohistochemical findings. Interestingly, subclinical PCV infections could be detected by single PCR with clinical samples that have been submitted from animals with irrelevant cases of respiratory and/or enteric problems. On the basis of the nucleotide sequences of PCV strains (PCV-2) recently associated with outbreaks of postweaning multisystemic wasting syndrome (PWMS) in Quebec, Canada, pig farms, other primers were designed from the PCV-1 genome, and these primers failed to amplify genomic fragments specific to the ORF1 or ORF2 genes of clinical isolates associated with PWMS but amplified DNA from the PCV-1 strain. Two rapid multiplex PCR (mPCR) methods have been developed to distinguish between both genotypes of PCV. By those two mPCR methods, (i) species-specific primer pairs were used to amplify a DNA fragment of 488 bp specific for the ORF2 genes of both genotypes, whereas a 375-bp fragment was amplified from the ORF1 gene of the PCV-1 strain only, or (ii) species-specific primer pairs were used to amplify a DNA fragment of 646 bp specific for the ORF1 genes of both genotypes, whereas a 425-bp fragment was amplified from the ORF2 gene of the PCV-1 strain only. By both mPCR methods, a PCV-2 infection was demonstrated in tissues of 94.2% (33 of 35) of the sick pigs tested, in agreement with previous findings showing the close association of this new genotype of PCV with outbreaks of PMWS in Europe and North America. On the other hand, a PCV-1 infection was confirmed in only 5.7% (2 of 35) of the pigs, and confirmation of a mixed infection with PCV-2 was obtained by a single PCR with PCV-2-specific primers.",,"['Ouardani, M.', 'Wilson, L.', 'Jetté, R.', 'Montpetit, C.', 'Dea, S.']",,,,
,PMC,Determination of Bovine Rotavirus G and P Serotypes in Italy by PCR,,PMC85835,,,"Determination of the G and P serotypes of group A bovine rotaviruses from 149 samples of feces or intestinal contents collected from calves showing clinical signs of neonatal diarrhea was performed by a nested reverse transcription-PCR typing assay. The G6 serotype was the most prevalent, accounting for viruses in 55.7% of the samples; viruses of the G10 and G8 serotypes were found in 34.9 and 4.7% of the samples, respectively. The virus in one sample (0.7%) was not classified due to concomitant infection with G6 and G8 strains, whereas viruses in six samples (4.0%) could not be characterized with any of the three G serotype-specific primers selected for the present study. When examined for their P-serotype specificities, viruses in 55 and 42.3% of the samples were characterized as P[11] and P[5], respectively, no P[1] serotype was identified, and viruses in 2.7% of the samples could not be classified due to multiple reactivity with both P[5]- and P[11]-specific primers. Various combinations of G and P serotypes were observed, the most frequent being G6,P[5] (38.3%), G10,P[11] (31.5%), and G6,P[11] (15.4%). The results of the present study, while contributing to a better understanding of the epidemiology of bovine rotaviruses in Italy, address the relevance of serotype specificity with regard to the constancy of the quality of bovine rotavirus vaccines under different field conditions.",,"['Falcone, E.', 'Tarantino, M.', 'Di Trani, L.', 'Cordioli, P.', 'Lavazza, A.', 'Tollis, M.']",,,,
,PMC,Baculovirus Stimulates Antiviral Effects in Mammalian Cells,,PMC113044,,,"Herein, we report that Autographa californica nucleopolyhedrovirus, a member of the Baculoviridae family, is capable of stimulating antiviral activity in mammalian cells. Baculoviruses are not pathogenic to mammalian cells. Nevertheless, live baculovirus is shown here to induce interferons (IFN) from murine and human cell lines and induces in vivo protection of mice from encephalomyocarditis virus infection. Monoclonal antibodies specific for the baculovirus envelope gp67 neutralize baculovirus-dependent IFN production. Moreover, UV treatment of baculovirus eliminates both infectivity and IFN-inducing activity. In contrast, the IFN-inducing activity of the baculovirus was unaffected by DNase or RNase treatment. These data demonstrate that IFN production can be induced in mammalian cells by baculovirus even though the cells fail to serve as a natural host for an active viral infection. Baculoviruses, therefore, provide a novel model in which to study at least one alternative mechanism for IFN induction in mammalian cells.",,"['Gronowski, Ann M.', 'Hilbert, David M.', 'Sheehan, Kathleen C. F.', 'Garotta, Gianni', 'Schreiber, Robert D.']",,,,
,PMC,Interaction of Hepatitis C Virus Core Protein with Viral Sense RNA and Suppression of Its Translation,,PMC113018,,,"To clarify the binding properties of hepatitis C virus (HCV) core protein and its viral RNA for the encapsidation, morphogenesis, and replication of HCV, the specific interaction of HCV core protein with its genomic RNA synthesized in vitro was examined in an in vivo system. The positive-sense RNA from the 5′ end to nucleotide (nt) 2327, which covers the 5′ untranslated region (5′UTR) and a part of the coding region of HCV structural proteins, interacted with HCV core protein, while no interaction was observed in the same region of negative-sense RNA and in other regions of viral and antiviral sense RNAs. The internal ribosome entry site (IRES) exists around the 5′UTR of HCV; therefore, the interaction of the core protein with this region of HCV RNA suggests that there is some effect on its cap-independent translation. Cells expressing HCV core protein were transfected with reporter RNAs consisting of nt 1 to 709 of HCV RNA (the 5′UTR of HCV and about two-thirds of the core protein coding regions) followed by a firefly luciferase gene (HCV07Luc RNA). The translation of HCV07Luc RNA was suppressed in cells expressing the core protein, whereas no significant suppression was observed in the case of a reporter RNA possessing the IRES of encephalomyocarditis virus followed by a firefly luciferase. This suppression by the core protein occurred in a dose-dependent manner. The expression of the E1 envelope protein of HCV or β-galactosidase did not suppress the translation of both HCV and EMCV reporter RNAs. We then examined the regions that are important for suppression of translation by the core protein and found that the region from nt 1 to 344 was enough to exert this suppression. These results suggest that the HCV core protein interacts with viral genomic RNA at a specific region to form nucleocapsids and regulates the expression of HCV by interacting with the 5′UTR.",,"['Shimoike, Takashi', 'Mimori, Shigetaka', 'Tani, Hideki', 'Matsuura, Yoshiharu', 'Miyamura, Tatsuo']",,,,
,PMC,Decreased metastatic spread in mice homozygous for a null allele of the cystatin C protease inhibitor gene.,,PMC395718,,,"AIMS: Increased or altered activities of cysteine proteases have been implicated in serious human disorders such as cancer, rheumatoid arthritis, sepsis, and osteoporosis. To improve the current knowledge of the regulatory role of a major mammalian cysteine protease inhibitor, cystatin C, in such disease processes, a cystatin C deficient mouse was generated and characterized. METHODS: The mouse cystatin C gene was inactivated by insertion of a bacterial neo gene through homologous recombination in 129/Sv embryonic stem cells. Embryonic stem cell clones were injected into C57BL/6J blastocysts followed by injection of the blastocysts into pseudopregnant female mice. F1 offspring with agouti coat colour after mating of chimaeric males with C57BL/6J females were examined by DNA analysis, and mice carrying the targeted mutation were intercrossed to obtain homozygous cystatin C deficient (CysC-/-) mice. To study the role of cysteine proteases and their inhibitors in metastasis, the spread of B16-F10 melanoma cells in CysC-/- and wild-type mice was compared. Analysis of the formation of remote metastases was carried out by intravenous injection of beta-galactosidase transfected B16-F10 cells and subsequent determination of cancer cell colonies in the lungs. RESULTS: Cystatin C deficient mice were fertile and showed no gross pathological abnormality up to 6 months of age. Compared with wild-type mice, seven times fewer large metastatic colonies were counted by means of a dissecting microscope in CysC-/- mice two weeks after tail vein injection of B16-F10 cells. At all of eight time points from 15 minutes to two weeks after intravenous injection of tumour cells, the CysC-/- mice had significantly fewer lung metastases. The observed differences were smaller when beta-galactosidase transfected cells were used to allow counting of small colonies. Subcutaneous and intracerebral tumour growth was not different in the CysC-/- mice. CONCLUSIONS: Cystatin C concentrations in vivo might influence metastasis in some tissues. The decreased metastatic spread of B16-F10 cells in CysC-/- mice is the result of both reduced seeding and reduced growth of tumour cells in their lungs.",,"['Huh, C G', 'Håkansson, K', 'Nathanson, C M', 'Thorgeirsson, U P', 'Jonsson, N', 'Grubb, A', 'Abrahamson, M', 'Karlsson, S']",,,,
,PMC,In vitro selection identifies key determinants for loop-loop interactions: RNA aptamers selective for the TAR RNA element of HIV-1.,,PMC1369882,,,"We selected RNA aptamers specific for the trans-activation responsive (TAR) RNA, a stem-loop structure crucial for the transcription of the integrated genome of the human immunodeficiency virus. Most of the selected sequences could be folded as imperfect hairpins and displayed a 5'-GUCCCAGA-3' consensus motif constituting the apical loop. The six central bases of this consensus sequence are complementary to the entire TAR loop, leading to the formation of TAR RNA-aptamer ""kissing"" complexes. The consensus G and A residues closing the aptamer loop contributed to the high affinity (Kd = 30 nM at 23 degrees C) of the aptamers for the TAR RNA. This G A pair was shown to be crucial for binding to TAR at a low magnesium concentration. The selection also identified 5'-PuPy and 5'-PyPu base pairs at alpha and beta positions of the stem, next to the loop, respectively. This strategy offered a way to identify key determinants of loop-loop interactions and to generate high affinity ligands of TAR RNA structure.",,"['Ducongé, F', 'Toulmé, J J']",,,,
,PMC,QUIZ CORNER,,PMC1540000,,,,,,,,,
,PMC,Nitric oxide and macrophage antiviral extrinsic activity,http://dx.doi.org/10.1046/j.1365-2567.1999.00864.x,PMC2326934,,,"In this study we evaluated the relationship between nitric oxide (NO) and macrophage antiviral extrinsic activity. Macrophages activated by intraperitoneal injection of herpes simplex virus-2 (HSV-2), showed both extrinsic antiviral activity and high nitrite production in contrast to non-activated, resident macrophages. The extrinsic antiviral activity was observed in cultures of Vero cells infected with HSV-1 and HSV-2. The NO inhibitor N-monomethyl-l-arginine acetate (l-NMA) impaired the antiviral activity of HSV-elicited macrophages. The effect was dose dependent and correlated with a reduction of nitrite in the culture media. The effect of l-NMA was reversed by the addition of l-arginine. These data indicate that NO could be responsible for the described activity. Furthermore, l-NMA treatment resulted in the aggravation of HSV-1-induced keratitis in the mouse model, supporting a defensive role of NO in the pathogenesis of HSV-1 corneal infection.",,"['Benencia, F', 'Courreges, M C']",,,,
,PMC,Dual Infection of Gnotobiotic Calves with Bovine Strains of Group A and Porcine-Like Group C Rotaviruses Influences Pathogenesis of the Group C Rotavirus,,PMC112963,,,"There is serological evidence that bovine group C rotaviruses exist in the United States, but there are no reports of their isolation. Ninety fecal samples from calves with diarrhea, 81 samples from adult cows with diarrhea (winter dysentery), and 20 fecal samples from healthy adult cows were tested for group C rotaviruses by polyacrylamide gel electrophoresis, immune electron microscopy, and reverse transcription-PCR (RT-PCR). Three samples from adult cow diarrhea cases were positive only by RT-PCR, and a group C rotavirus was isolated from a positive sample in monkey kidney (MA104) cells (WD534tc/C). Genetically and serologically, the WD534tc/C strain was more closely related to the Cowden porcine group C strain than to the Shintoku bovine strain. Because the original cow feces also contained a group A rotavirus (detected after passage in cell culture), we hypothesized that such dual-rotavirus infections might play a role in the pathogenesis and host adaptation of rotaviruses. Thus, we examined the pathogenesis of WD534tc/C alone or combined with virulent (IND/A) or attenuated (NCDV/A) bovine group A rotaviruses in gnotobiotic calves. WD534tc/C alone induced diarrhea without (or with limited) virus shedding in inoculated calves (n = 3). In contrast, all calves coinfected with WD534tc/C and IND/A (n = 2) developed diarrhea and shed both viruses, whereas calves coinfected with WD534tc/C and NCDV/A (n = 3) developed diarrhea but did not shed either virus. Infection with WD534tc/C or NCDV/A alone caused only mild villous atrophy (jejunum and/or ileum), whereas dual infection with both viruses induced lesions throughout the small intestine. Although IND/A alone caused villous atrophy, more-widespread small intestinal lesions occurred in calves coinfected with WD534tc/C and IND/A. In conclusion, coinfection of calves with group A rotaviruses enhanced fecal shedding of a bovine group C rotavirus and the extent of histopathological lesions in the small intestines. Thus, our findings suggest a potential novel hypothesis involving dual infections for the adaptation of heterologous rotaviruses to new host species.",,"['Chang, K. O.', 'Nielsen, P. R.', 'Ward, L. A.', 'Saif, L. J.']",,,,
,PMC,Replication-Defective Bovine Adenovirus Type 3 as an Expression Vector,,PMC112946,,,"Although recombinant human adenovirus (HAV)-based vectors offer several advantages for somatic gene therapy and vaccination over other viral vectors, it would be desirable to develop alternative vectors with prolonged expression and decreased toxicity. Toward this objective, a replication-defective bovine adenovirus type 3 (BAV-3) was developed as an expression vector. Bovine cell lines designated VIDO R2 (HAV-5 E1A/B-transformed fetal bovine retina cell [FBRC] line) and 6.93.9 (Madin-Darby bovine kidney [MDBK] cell line expressing E1 proteins) were developed and found to complement the E1A deletion in BAV-3. Replication-defective BAV-3 with a 1.7-kb deletion removing most of the E1A and E3 regions was constructed. This virus could be grown in VIDO R2 or 6.93.9 cells but not in FBRC or MDBK cells. The results demonstrated that the E1 region of HAV-5 has the capacity to transform bovine retina cells and that the E1A region of HAV-5 can complement that of BAV-3. A replication-defective BAV-3 vector expressing bovine herpesvirus type 1 glycoprotein D from the E1A region was made. A similar replication-defective vector expressing the hemagglutinin-esterase gene of bovine coronavirus from the E3 region was isolated. Although these viruses grew less efficiently than the replication-competent recombinant BAV-3 (E3 deleted), they are suitable for detailed studies with animals to evaluate the safety, duration of foreign gene expression, and ability to induce immune responses. In addition, a replication-competent recombinant BAV-3 expressing green fluorescent protein was constructed and used to evaluate the host range of BAV-3 under cell culture conditions. The development of bovine E1A-complementing cell lines and the generation of replication-defective BAV-3 vectors is a major technical advancement for defining the use of BAV-3 as vector for vaccination against diseases of cattle and somatic gene therapy in humans.",,"['Reddy, P. Seshidhar', 'Idamakanti, Neeraja', 'Chen, Yan', 'Whale, Tyler', 'Babiuk, Lorne A.', 'Mehtali, Majid', 'Tikoo, Suresh Kumar']",,,,
,PMC,"Polypyrimidine Tract-Binding Protein Binds to the Complementary Strand of the Mouse Hepatitis Virus 3′ Untranslated Region,  Thereby Altering RNA Conformation",,PMC112943,,,"Mouse hepatitis virus (MHV) RNA transcription is regulated mainly by the leader and intergenic (IG) sequences. However, a previous study has shown that the 3′ untranslated region (3′-UTR) of the viral genome is also required for subgenomic mRNA transcription; deletion of nucleotides (nt) 270 to 305 from the 3′-UTR completely abolished subgenomic mRNA transcription without affecting minus-strand RNA synthesis (Y.-J. Lin, X. Zhang, R.-C. Wu, and M. M. C. Lai, J. Virol. 70:7236–7240, 1996), suggesting that the 3′-UTR affects positive-strand RNA synthesis. In this study, by UV-cross-linking experiments, we found that several cellular proteins bind specifically to the minus-strand 350 nucleotides complementary to the 3′-UTR of the viral genome. The major protein species, p55, was identified as the polypyrimidine tract-binding protein (PTB, also known as heterogeneous nuclear RNP I) by immunoprecipitation of the UV-cross-linked protein and binding of the recombinant PTB. A strong PTB-binding site was mapped to nt 53 to 149, and another weak binding site was mapped to nt 270 to 307 on the complementary strand of the 3′-UTR (c3′-UTR). Partial substitutions of the PTB-binding nucleotides reduced PTB binding in vitro. Furthermore, defective interfering (DI) RNAs harboring these mutations showed a substantially reduced ability to synthesize subgenomic mRNA. By enzymatic and chemical probing, we found that PTB binding to nt 53 to 149 caused a conformational change in the neighboring RNA region. Partial deletions within the PTB-binding sequence completely abolished the PTB-induced conformational change in the mutant RNA even when the RNA retained partial PTB-binding activity. Correspondingly, the MHV DI RNAs containing these deletions completely lost their ability to transcribe mRNAs. Thus, the conformational change in the c3′-UTR caused by PTB binding may play a role in mRNA transcription.",,"['Huang, Peiyong', 'Lai, Michael M. C.']",,,,
,PMC,Arterivirus discontinuous mRNA transcription is guided by base pairing between sense and antisense transcription-regulating sequences,,PMC18411,,,"To generate an extensive set of subgenomic (sg) mRNAs, nidoviruses (arteriviruses and coronaviruses) use a mechanism of discontinuous transcription. During this process, mRNAs are generated that represent the genomic 5′ sequence, the so-called leader RNA, fused at specific positions to different 3′ regions of the genome. The fusion of the leader to the mRNA bodies occurs at a short, conserved sequence element, the transcription-regulating sequence (TRS), which precedes every transcription unit in the genome and is also present at the 3′ end of the leader sequence. Here, we have used site-directed mutagenesis of the infectious cDNA clone of the arterivirus equine arteritis virus to show that sg mRNA synthesis requires a base-pairing interaction between the leader TRS and the complement of a body TRS in the viral negative strand. Mutagenesis of the body TRS of equine arteritis virus RNA7 reduced sg RNA7 transcription severely or abolished it completely. Mutations in the leader TRS dramatically influenced the synthesis of all sg mRNAs. The construction of double mutants in which a mutant leader TRS was combined with the corresponding mutant RNA7 body TRS resulted in the specific restoration of mRNA7 synthesis. The analysis of the mRNA leader–body junctions of a number of mutants with partial transcriptional activity provided support for a mechanism of discontinuous minus-strand transcription that resembles similarity-assisted, copy-choice RNA recombination.",,"['van Marle, Guido', 'Dobbe, Jessika C.', 'Gultyaev, Alexander P.', 'Luytjes, Willem', 'Spaan, Willy J. M.', 'Snijder, Eric J.']",,,,
,PMC,Early life origins of asthma,,PMC408565,,,,,"['Gern, James E.', 'Lemanske, Robert F.', 'Busse, William W.']",,,,
,PMC,Human major group rhinoviruses downmodulate the accessory function of monocytes by inducing IL-10,,PMC408557,,,"Human rhinoviruses (HRVs) are the predominant cause of the common cold. Although this disease is per se rather harmless, HRV infection is considered to set the stage for more dangerous pathogens in vivo. Here we demonstrate that HRV-14, a member of the major group HRV family, can efficiently inhibit antigen-induced T-cell proliferation and T-cell responses to allogeneic monocytes. HRV-14 triggered a significant downregulation of MHC class II molecules on monocytes. Moreover, supernatants from monocytes cultured in the presence of HRV-14 strongly reduced the allogeneic T-cell stimulatory property of untreated monocytes and monocyte-derived dendritic cells (md-DCs), whereas Epstein Barr virus–transformed B-lymphoblastoid cells were not sensitive. Analysis of the supernatant revealed that HRV-14 induced the production of significant amounts of the immunosuppressive cytokine IL-10. The important T-cell stimulatory cytokine IL-12 or the proinflammatory cytokines IL-1β or TNF-α were not detected or were only minimally detected. Finally, monocytes pretreated with HRV-14 were greatly inhibited in their production of IL-12 upon stimulation with IFN-γ/LPS. These observations suggest that altered cytokine production in mononuclear phagocytes upon interaction with HRV downmodulates appropriate immune responses during the viral infection.",,"['Stöckl, Johannes', 'Vetr, Helga', 'Majdic, Otto', 'Zlabinger, Gerhard', 'Kuechler, Ernst', 'Knapp, Walter']",,,,
,PMC,Isolation of Helicobacter canis from a Colony of Bengal Cats with Endemic Diarrhea,,PMC85546,,,"On the basis of biochemical, phenotypic, and 16S rRNA analyses, Helicobacter canis was isolated from Bengal cats with and without chronic diarrhea. Because the cats were coinfected with other potential pathogens, including Campylobacter helveticus, and because H. canis was isolated from nondiarrheic cats, the causal role of H. canis in producing the diarrhea could not be proven. Histologically, the colons of the four affected cats were characterized by mild to moderate neutrophilic, plasmacytic, and histocytic infiltrates in the lamina propria. Rare crypt abscesses were also noted for three cats but were a more prominent feature of the colonic lesions noted for the fourth cat. This is the first observation of H. canis in cats and raises the possibility that H. canis, like H. hepaticus and H. bilis in mice, can cause inflammation of the colon, particularly in hosts with immune dysregulation. Further studies are needed to determine the importance of H. canis as a primary enteric pathogen in cats and the role of cats in the possible zoonotic spread of H. canis to humans.",,"['Foley, Janet E.', 'Marks, Stanley L.', 'Munson, Linda', 'Melli, Ann', 'Dewhirst, Floyd E.', 'Yu, Shilu', 'Shen, Zeli', 'Fox, James G.']",,,,
,PMC,Mutational Analysis of the Putative Fusion Domain of Ebola Virus Glycoprotein,,PMC112919,,,"Ebola viruses contain a single glycoprotein (GP) spike, which functions as a receptor binding and membrane fusion protein. It contains a highly conserved hydrophobic region (amino acids 524 to 539) located 24 amino acids downstream of the N terminus of the Ebola virus GP2 subunit. Comparison of this region with the structural features of the transmembrane subunit of avian retroviral GPs suggests that the conserved Ebola virus hydrophobic region may, in fact, serve as the fusion peptide. To test this hypothesis directly, we introduced conservative (alanine) and nonconservative (arginine) amino acid substitutions at eight positions in this region of the GP2 molecule. The effects of these mutations were deduced from the ability of the Ebola virus GP to complement the infectivity of a vesicular stomatitis virus (VSV) lacking the receptor-binding G protein. Some mutations, such as Ile-to-Arg substitutions at positions 532 (I532R), F535R, G536A, and P537R, almost completely abolished the ability of the GP to support VSV infectivity without affecting the transport of GP to the cell surface and its incorporation into virions or the production of virus particles. Other mutations, such as G528R, L529A, L529R, I532A, and F535A, reduced the infectivity of the VSV-Ebola virus pseudotypes by at least one-half. These findings, together with previous reports of liposome association with a peptide corresponding to positions 524 to 539 in the GP molecule, offer compelling support for a fusion peptide role for the conserved hydrophobic region in the Ebola virus GP.",,"['Ito, Hiroshi', 'Watanabe, Shinji', 'Sanchez, Anthony', 'Whitt, Michael A.', 'Kawaoka, Yoshihiro']",,,,
,PMC,"Macrophage Infiltration, but Not Apoptosis, Is Correlated with Immune-Mediated Demyelination following Murine  Infection with a Neurotropic Coronavirus",,PMC112898,,,"Mice infected with mouse hepatitis virus strain JHM (MHV-JHM) develop a chronic demyelinating encephalomyelitis that is in large part immune mediated. Potential mechanisms of immune activity were assessed using an adoptive transfer system. Mice deficient in recombinase-activating gene function (RAG1(−/−)), defective in B- and T-cell maturation, become persistently infected with MHV but do not develop demyelination. Adoptive transfer of splenocytes from mice immunized to MHV into RAG1(−/−) mice infected with an attenuated strain of the virus results in the rapid and progressive development of demyelination. Most striking, adoptive transfer resulted, within 5 to 6 days, in extensive recruitment of activated macrophages/microglia to sites of demyelination within the spinal cord. Clearance of virus antigen occurred preferentially from the gray matter of the spinal cord. Apoptotic cells were identified in both the gray and white matter of the central nervous system (CNS) from RAG1(−/−) mice before and after adoptive transfer, with a moderate increase in number, but not distribution, of apoptotic cells following the development of demyelination. These results suggest that apoptosis following MHV-JHM infection of the murine CNS is not sufficient to cause demyelination. These results, showing that macrophage recruitment and myelin destruction occur rapidly after immune reconstitution of RAG(−/−) mice, suggest that this will be a useful system for investigating MHV-induced demyelination.",,"['Wu, Gregory F.', 'Perlman, Stanley']",,,,
,PMC,Carboxypeptidase D Is an Avian Hepatitis B Virus Receptor,,PMC112890,,,"The receptor molecules for human and animal hepatitis B viruses have not been defined. Previous studies have described a 170 to 180 kDa molecule (p170 or gp180) that binds in vitro to the pre-S domain of the large envelope protein of duck hepatitis B virus (DHBV); cDNA cloning revealed the binding protein to be duck carboxypeptidase D (DCPD). In the present study, the DCPD cDNA was transfected into several nonpermissive human-, monkey-, and avian species-derived cell lines. Cells transfected with a plasmid encoding the full-length DCPD protein bound DHBV particles, whereas cells expressing truncated versions of DCPD protein that fail to bind the pre-S protein did not. The DHBV binding to DCPD-reconstituted cells was blocked by a monoclonal antibody that neutralizes DHBV infection of primary duck hepatocytes (PDH) and also by a pre-S peptide previously shown to inhibit DHBV infection of PDH. In addition to promoting virus binding, DCPD expression was associated with internalization of viral particles. The entry process was prevented by incubation of reconstituted cells with DHBV at 4°C and by the addition of energy-depleting agents known to block DHBV entry into PDH. These results demonstrated that DCPD is a DHBV receptor. However, the lack of complete viral replication in DCPD-reconstituted cells suggested that additional factors are required for postentry events in immortalized cell lines.",,"['Tong, Shuping', 'Li, Jisu', 'Wands, Jack R.']",,,,
,PMC,A Phylogenetically Conserved Hairpin-Type 3′ Untranslated Region Pseudoknot Functions in Coronavirus RNA Replication,,PMC112852,,,"Secondary and tertiary structures in the 3′ untranslated region (UTR) of plus-strand RNA viruses have been postulated to function as control elements in RNA replication, transcription, and translation. Here we describe a 54-nucleotide (nt) hairpin-type pseudoknot within the 288-nt 3′ UTR of the bovine coronavirus genome and show by mutational analysis of both stems that the pseudoknotted structure is required for the replication of a defective interfering RNA genome. The pseudoknot is phylogenetically conserved among coronaviruses both in location and in shape but only partially in nucleotide sequence, and evolutionary covariation of bases to maintain G · U pairings indicates that it functions in the plus strand. RNase probing of synthetic transcripts provided additional evidence of its tertiary structure and also identified the possible existence of two conformational states. These results indicate that the 3′ UTR pseudoknot is involved in coronavirus RNA replication and lead us to postulate that it functions as a regulatory control element.",,"['Williams, Gwyn D.', 'Chang, Ruey-Yi', 'Brian, David A.']",,,,
,PMC,Amino Acid Substitutions within the Leucine Zipper Domain of the Murine Coronavirus Spike Protein Cause Defects in Oligomerization and the Ability To Induce  Cell-to-Cell Fusion,,PMC112832,,,"The murine coronavirus spike (S) protein contains a leucine zipper domain which is highly conserved among coronaviruses. To assess the role of this leucine zipper domain in S-induced cell-to-cell fusion, the six heptadic leucine and isoleucine residues were replaced with alanine by site-directed mutagenesis. The mutant S proteins were analyzed for cell-to-cell membrane fusion activity as well as for progress through the glycoprotein maturation process, including intracellular glycosylation, oligomerization, and cell surface expression. Single-alanine-substitution mutations had minimal, if any, effects on S-induced cell-to-cell fusion. Significant reduction in fusion activity was observed, however, when two of the four middle heptadic leucine or isoleucine residues were replaced with alanine. Double alanine substitutions that involved either of the two end heptadic leucine residues did not significantly affect fusion. All double-substitution mutant S proteins displayed levels of endoglycosidase H resistance and cell surface expression similar to those of the wild-type S. However, fusion-defective double-alanine-substitution mutants exhibited defects in S oligomerization. These results indicate that the leucine zipper domain plays a role in S-induced cell-to-cell fusion and that the ability of S to induce fusion may be dependent on the oligomeric structure of S.",,"['Luo, Zongli', 'Matthews, Avery M.', 'Weiss, Susan R.']",,,,
,PMC,"The First Immunoglobulin-Like Domain of HveC Is Sufficient To Bind Herpes Simplex Virus gD with Full Affinity, While the Third  Domain Is Involved in Oligomerization of HveC",,PMC112829,,,"The human herpesvirus entry mediator C (HveC/PRR1) is a member of the immunoglobulin family used as a cellular receptor by the alphaherpesviruses herpes simplex virus (HSV), pseudorabies virus, and bovine herpesvirus type 1. We previously demonstrated direct binding of the purified HveC ectodomain to purified HSV type 1 (HSV-1) and HSV-2 glycoprotein D (gD). Here, using a baculovirus expression system, we constructed and purified truncated forms of the receptor containing one [HveC(143t)], two [HveC(245t)], or all three immunoglobulin-like domains [HveC(346t)] of the extracellular region. All three constructs were equally able to compete with HveC(346t) for gD binding. The variable domain bound to virions and blocked HSV infection as well as HveC(346t). Thus, all of the binding to the receptor occurs within the first immunoglobulin-like domain, or V-domain, of HveC. These data confirm and extend those of Cocchi et al. (F. Cocchi, M. Lopez, L. Menotti, M. Aoubala, P. Dubreuil, and G. Campadelli-Fiume, Proc. Natl. Acad. Sci. USA 95:15700, 1998). Using biosensor analysis, we measured the affinity of binding of gD from HSV strains KOS and rid1 to two forms of HveC. Soluble gDs from the KOS strain of HSV-1 had the same affinity for HveC(346t) and HveC(143t). The mutant gD(rid1t) had an increased affinity for HveC(346t) and HveC(143t) due to a faster rate of complex formation. Interestingly, we found that HveC(346t) was a tetramer in solution, whereas HveC(143t) and HveC(245t) formed dimers, suggesting a role for the third immunoglobulin-like domain of HveC in oligomerization. In addition, the stoichiometry between gD and HveC appeared to be influenced by the level of HveC oligomerization.",,"['Krummenacher, Claude', 'Rux, Ann H.', 'Whitbeck, J. Charles', 'Ponce-de-Leon, Manuel', 'Lou, Huan', 'Baribaud, Isabelle', 'Hou, Wangfang', 'Zou, Changhua', 'Geraghty, Robert J.', 'Spear, Patricia G.', 'Eisenberg, Roselyn J.', 'Cohen, Gary H.']",,,,
,PMC,"Translation from the 5′ Untranslated Region (UTR) of mRNA 1 Is Repressed, but That from the 5′ UTR of mRNA 7  Is Stimulated in Coronavirus-Infected Cells",,PMC112815,,,"Viral gene products are generally required in widely differing amounts for successful virus growth and assembly. For coronaviruses, regulation of transcription is a major contributor to these differences, but regulation of translation may also be important. Here, we examine the possibility that the 5′ untranslated regions (UTRs), unique for each of the nine species of mRNA in the bovine coronavirus and ranging in length from 70 nucleotides (nt) to 210 nt (inclusive of the common 5′-terminal 65-nt leader), can differentially affect the rate of protein accumulation. When the natural 77-nt 5′ UTR on synthetic transcripts of mRNA 7 (mRNA for N and I proteins) was replaced with the 210-nt 5′ UTR from mRNA 1 (genomic RNA, mRNA for viral polymerase), approximately twofold-less N, or (N) CAT fusion reporter protein, was made in vitro. Twofold less was also made in vivo in uninfected cells when a T7 RNA polymerase-driven transient-transfection system was used. In coronavirus-infected cells, this difference surprisingly became 12-fold as the result of both a stimulated translation from the 77-nt 5′ UTR and a repression of translation from the 210-nt 5′ UTR. These results reveal that a differential 5′ UTR-directed regulation of translation can occur in coronavirus-infected cells and lead us to postulate that the direction and degree of regulation is carried out by viral or virally induced cellular factors acting in trans on cis-acting elements within the 5′ UTR.",,"['Senanayake, Savithra D.', 'Brian, David A.']",,,,
,PMC,Regulation of Closterovirus Gene Expression Examined by Insertion of a Self-Processing Reporter and by Northern Hybridization,,PMC112813,,,"A reporter open reading frame (ORF) coding for a fusion of bacterial β-glucuronidase (GUS) with a proteinase domain (Pro) derived from tobacco etch potyvirus was utilized for tagging individual genes of beet yellows closterovirus (BYV). Insertion of this reporter ORF between the first and second codons of the BYV ORFs encoding the HSP70 homolog (HSP70h), a major capsid protein (CP), and a 20-kDa protein (p20) resulted in the expression of the processed GUS-Pro reporter from corresponding subgenomic RNAs. The high sensitivity of GUS assays permitted temporal analysis of reporter accumulation, revealing early expression from the HSP70h promoter, followed by the CP promoter and later the p20 promoter. The kinetics of transcription of the remaining BYV genes encoding a 64-kDa protein (p64), a minor capsid protein (CPm), and a 21-kDa protein (p21) were examined via Northern blot analysis. Taken together, the data indicated that the temporal regulation of BYV gene expression includes early (HSP70h, CPm, CP, and p21 promoters) and late (p64 and p20 promoters) phases. It was also demonstrated that the deletion of six viral genes that are nonessential for RNA amplification resulted in a dramatic increase in the level of transcription from one of the two remaining subgenomic promoters. Comparison with other positive-strand RNA viruses producing multiple subgenomic RNAs showed the uniqueness of the pattern of closterovirus transcriptional regulation.",,"['Hagiwara, Yuka', 'Peremyslov, Valery V.', 'Dolja, Valerian V.']",,,,
,PMC,Structural Maturation of the Transmissible Gastroenteritis Coronavirus,,PMC112809,,,"During the life cycle of the transmissible gastroenteritis coronavirus (TGEV), two types of virus-related particles are detected in infected swine testis cells: large annular viruses and small dense viruses. We have studied the relationships between these two types of particles. Immunoelectron microscopy showed that they are closely related, since both large and small particles reacted equally with polyclonal and monoclonal antibodies specific for TGEV proteins. Monensin, a drug that selectively affects the Golgi complex, caused an accumulation of large annular viral particles in perinuclear elements of the endoplasmic reticulum-Golgi intermediate compartment. A partial reversion of the monensin blockade was obtained in both the absence and presence of cycloheximide, a drug that prevented the formation of new viral particles. After removal of monensin, the Golgi complex recovered its perinuclear location, and a decrease in the number of perinuclear large viral particles was observed. The release of small dense viral particles into secretory vesicles and the extracellular medium was also observed, as was a partial recovery of infectivity in culture supernatants. Small viral particles started to be seen between the third and the fourth Golgi cisternae of normally infected cells. All of these data strongly indicate that the large annular particles are the immature precursors of the small dense viruses, which are the infectious TGEV virions. The immature viral particles need to reach a particular location at the trans side of the Golgi stack to complete their morphological maturation.",,"['Salanueva, Iñigo J.', 'Carrascosa, José L.', 'Risco, Cristina']",,,,
,PMC,A coding RNA sequence acts as a replication signal in cardioviruses,,PMC18073,,,"Theiler’s virus and Mengo virus are representatives of the Cardiovirus genus within the picornavirus family. Their genome is an 8-kilobase long positive strand RNA molecule. This RNA molecule plays three roles in infected cells: It serves as a messenger RNA, acts as a template for genome replication, and is encapsidated to form progeny virions. We observed that a cis-acting signal required for replication of Theiler’s virus was contained within a 130-nt stretch of the region encoding the capsid protein VP2. This RNA sequence does not influence internal ribosome entry site-mediated translation initiation and thus likely acts directly as a signal for the replication complex. We found a similar signal in the VP2-coding sequence of Mengo virus, and both signals could be functionally exchanged. Within the replication element, a 9-nt sequence that is highly conserved among cardioviruses was shown to be essential for replication. This conserved sequence was contained in mostly unpaired regions of the RNA secondary structure predicted for the replication elements of the various cardioviruses. Interestingly, a similar replication element has been reported to occur in the distantly related human rhinovirus type 14, suggesting that such elements could be conserved throughout the picornavirus family. However, the different location of the replication elements in rhinovirus and cardioviruses, and the fact that they were not functionally exchangeable, is raising intriguing questions about the evolution of such signals in picornaviruses.",,"['Lobert, Pierre-Emmanuel', 'Escriou, Nicolas', 'Ruelle, Jean', 'Michiels, Thomas']",,,,
,PMC,"A questionnaire on the health, management, and performance of cow-calf herds in Québec.",,PMC1539859,,,"Questionnaires were mailed to 520 cow-calf producers in Québec in order to compare management practices and herd performance according to herd size (small: < 40 females, or large: > or = 40 females) and in 4 geographic areas for the 1995 calving season. Owners of large herds adopted management practice and preventive measures more often than did owners of small herds. Average calving and weaning rates were 95% and 87% respectively. Average perinatal and preweaning mortality rates were between 4.9% and 5.6%. A greater percentage of owners with large herds than owners of small herds reported diarrhea and pneumonia problems. Among large herds, the number of herds experiencing pneumonia and calf mortality associated with diarrhea tended to be higher in areas of the northwest. Calf mortality due to pneumonia was higher in the northeast. No regional variation was found among small herds. Further research is needed to identify diseases risk factors.",,"['Dutil, L', 'Fecteau, G', 'Bouchard, E', 'Dutremblay, D', 'Paré, J']",,,,
,PMC,"A new animal model for relapsing polychondritis, induced by cartilage matrix protein (matrilin-1)",,PMC408533,,,"Relapsing polychondritis (RP) differs from rheumatoid arthritis (RA) in that primarily cartilage outside diarthrodial joints is affected. The disease usually involves trachea, nose, and outer ears. To investigate whether the tissue distribution of RP may be explained by a specific immune response, we immunized rats with cartilage matrix protein (matrilin-1), a protein predominantly expressed in tracheal cartilage. After 2–3 weeks, some rats developed a severe inspiratory stridor. They had swollen noses and/or epistaxis, but showed neither joint nor outer ear affection. The inflammatory lesions involved chronic active erosions of cartilage. Female rats were more susceptible than males. The disease susceptibility was controlled by both MHC genes (f, l, d, and a haplotypes are high responders, and u, n, and c are resistant) and non-MHC genes (the LEW strain is susceptible; the DA strain is resistant). However, all strains mounted a pronounced IgG response to cartilage matrix protein. The initiation and effector phase of the laryngotracheal involvement causing the clinical symptoms were shown to depend on αβ T cells. Taken together, these results represent a novel model for RP: matrilin-1–induced RP. Our findings also suggest that different cartilage proteins are involved in pathogenic models of RP and RA.",,"['Hansson, Ann-Sofie', 'Heinegård, Dick', 'Holmdahl, Rikard']",,,,
,PMC,Genotypes of Canine Distemper Virus Determined by Analysis of the Hemagglutinin Genes of Recent Isolates  from Dogs in Japan,,PMC85418,,,"Canine distemper of domestic dogs is caused by canine distemper virus (CDV), a member of the morbilliviruses. It has been a highly contagious disease of great veterinary importance for centuries, but for the last several decades it has been controlled satisfactorily by modified live vaccines. In the 1990s, however, it was described that CDV strains genetically different from vaccine strains may have caused the disease in vaccinated dogs. The highest antigenic variation is found in the H protein. Therefore, in the present study, hemagglutinin (H) genes obtained from current vaccines and field isolates and amplified directly from clinical specimens were genetically analyzed by restriction fragment length polymorphism assay and sequencing. Phylogenetic analysis of the H-gene amino acid sequences revealed that at least two CDV genotypes are circulating among dogs in Japan; one is a genotype to which almost all Japanese CDV isolates belong and the other has not been previously described. Both are separate and independent from the other lineages or genotypes of vaccine strains, as well as European and U.S. CDV isolates. The results suggest that CDV has also evolved in Japan, and further studies will be needed for an evaluation and possible improvement of the efficacies of current CDV vaccines.",,"['Mochizuki, Masami', 'Hashimoto, Michiru', 'Hagiwara, Shigeyuki', 'Yoshida, Yoshio', 'Ishiguro, Shinryo']",,,,
,PMC,Induction of Apoptosis in Murine Coronavirus-Infected Cultured Cells and Demonstration of E Protein as an Apoptosis Inducer,,PMC104316,,,"We demonstrated that infection of 17Cl-1 cells with the murine coronavirus mouse hepatitis virus (MHV) induced caspase-dependent apoptosis. MHV-infected DBT cells did not show apoptotic changes, indicating that apoptosis was not a universal mechanism of cell death in MHV-infected cells. Expression of MHV structural proteins by recombinant vaccinia viruses showed that expression of MHV E protein induced apoptosis in DBT cells, whereas expression of other MHV structural proteins, including S protein, M protein, N protein, and hemagglutinin-esterase protein, failed to induce apoptosis. MHV E protein-mediated apoptosis was suppressed by a high level of Bcl-2 oncogene expression. Our data showed that MHV E protein is a multifunctional protein; in addition to its known function in coronavirus envelope formation, it also induces apoptosis.",,"['An, Sungwhan', 'Chen, Chun-Jen', 'Yu, Xin', 'Leibowitz, Julian L.', 'Makino, Shinji']",,,,
,PMC,Pathogenesis of Chimeric MHV4/MHV-A59 Recombinant Viruses:  the Murine Coronavirus Spike Protein Is a Major  Determinant of Neurovirulence,,PMC104302,,,"The mouse hepatitis virus (MHV) spike glycoprotein, S, has been implicated as a major determinant of viral pathogenesis. In the absence of a full-length molecular clone, however, it has been difficult to address the role of individual viral genes in pathogenesis. By using targeted RNA recombination to introduce the S gene of MHV4, a highly neurovirulent strain, into the genome of MHV-A59, a mildly neurovirulent strain, we have been able to directly address the role of the S gene in neurovirulence. In cell culture, the recombinants containing the MHV4 S gene, S4R22 and S4R21, exhibited a small-plaque phenotype and replicated to low levels, similar to wild-type MHV4. Intracranial inoculation of C57BL/6 mice with S4R22 and S4R21 revealed a marked alteration in pathogenesis. Relative to wild-type control recombinant viruses (wtR13 and wtR9), containing the MHV-A59 S gene, the MHV4 S gene recombinants exhibited a dramatic increase in virulence and an increase in both viral antigen staining and inflammation in the central nervous system. There was not, however, an increase in the level of viral replication in the brain. These studies demonstrate that the MHV4 S gene alone is sufficient to confer a highly neurovirulent phenotype to a recombinant virus deriving the remainder of its genome from a mildly neurovirulent virus, MHV-A59. This definitively confirms previous findings, suggesting that the spike is a major determinant of pathogenesis.",,"['Phillips, Joanna J.', 'Chua, Ming Ming', 'Lavi, Ehud', 'Weiss, Susan R.']",,,,
,PMC,Fish Rhabdovirus Cell Entry Is Mediated by Fibronectin,,PMC104297,,,"Three monoclonal antibodies (MAbs) generated against rainbow trout gonad cells (RTG-2) have been selected for their ability to protect cells from the viral hemorrhagic septicemia virus (VHSV) infection, a salmonid rhabdovirus. Protection from infection was restricted to the salmonid-derived cell lines indicating species specificity of the blocking MAbs. Surprisingly, the blocking activity of these MAbs was also effective against other nonantigenically related fish rhabdoviruses. Indirect immunofluorescence and immunoelectron microscopy observations demonstrated that the three MAbs were all directed against an abundant cell plasma membrane component, and immunoprecipitation studies indicated that the target consisted of a heterodimeric complex with molecular masses of 200 and 44 kDa. Biochemical data provided the following evidence that fibronectin is part of this complex and that it could represent the main receptor for fish rhabdoviruses. (i) An antiserum generated against the 200-kDa protein reacted against the recombinant rainbow trout fibronectin expressed in Escherichia coli. (ii) The purified rainbow trout fibronectin was able to bind specifically to VHSV. To our knowledge, this is the first identification of a cellular component acting as a primary receptor for a virus replicating in lower vertebrates and, more interestingly, for viruses belonging to the Rhabdoviridae family.",,"['Bearzotti, Monique', 'Delmas, Bernard', 'Lamoureux, Annie', 'Loustau, Anne-Marie', 'Chilmonczyk, Stefan', 'Bremont, Michel']",,,,
,PMC,A Recombinant Hepatitis C Virus RNA-Dependent RNA Polymerase Capable of Copying the Full-Length Viral RNA,,PMC104296,,,"All of the previously reported recombinant RNA-dependent RNA polymerases (RdRp), the NS5B enzymes, of hepatitis C virus (HCV) could function only in a primer-dependent and template-nonspecific manner, which is different from the expected properties of the functional viral enzymes in the cells. We have now expressed a recombinant NS5B that is able to synthesize a full-length HCV genome in a template-dependent and primer-independent manner. The kinetics of RNA synthesis showed that this RdRp can initiate RNA synthesis de novo and yield a full-length RNA product of genomic size (9.5 kb), indicating that it did not use the copy-back RNA as a primer. This RdRp was also able to accept heterologous viral RNA templates, including poly(A)- and non-poly(A)-tailed RNA, in a primer-independent manner, but the products in these cases were heterogeneous. The RdRp used some homopolymeric RNA templates only in the presence of a primer. By using the 3′-end 98 nucleotides (nt) of HCV RNA, which is conserved in all genotypes of HCV, as a template, a distinct RNA product was generated. Truncation of 21 nt from the 5′ end or 45 nt from the 3′ end of the 98-nt RNA abolished almost completely its ability to serve as a template. Inclusion of the 3′-end variable sequence region and the U-rich tract upstream of the X region in the template significantly enhanced RNA synthesis. The 3′ end of minus-strand RNA of HCV genome also served as a template, and it required a minimum of 239 nt from the 3′ end. These data defined the cis-acting sequences for HCV RNA synthesis at the 3′ end of HCV RNA in both the plus and minus senses. This is the first recombinant HCV RdRp capable of copying the full-length HCV RNA in the primer-independent manner expected of the functional HCV RNA polymerase.",,"['Oh, Jong-Won', 'Ito, Takayoshi', 'Lai, Michael M. C.']",,,,
,PMC,Localization of Mouse Hepatitis Virus Nonstructural Proteins and RNA Synthesis Indicates a Role for Late  Endosomes in Viral Replication,,PMC104292,,,"The aim of the present study was to define the site of replication of the coronavirus mouse hepatitis virus (MHV). Antibodies directed against several proteins derived from the gene 1 polyprotein, including the 3C-like protease (3CLpro), the putative polymerase (POL), helicase, and a recently described protein (p22) derived from the C terminus of the open reading frame 1a protein (CT1a), were used to probe MHV-infected cells by indirect immunofluorescence (IF) and electron microscopy (EM). At early times of infection, all of these proteins showed a distinct punctate labeling by IF. Antibodies to the nucleocapsid protein also displayed a punctate labeling that largely colocalized with the replicase proteins. When infected cells were metabolically labeled with 5-bromouridine 5′-triphosphate (BrUTP), the site of viral RNA synthesis was shown by IF to colocalize with CT1a and the 3CLpro. As shown by EM, CT1a localized to LAMP-1 positive late endosomes/lysosomes while POL accumulated predominantly in multilayered structures with the appearance of endocytic carrier vesicles. These latter structures were also labeled to some extent with both anti-CT1a and LAMP-1 antibodies and could be filled with fluid phase endocytic tracers. When EM was used to determine sites of BrUTP incorporation into viral RNA at early times of infection, the viral RNA localized to late endosomal membranes as well. These results demonstrate that MHV replication occurs on late endosomal membranes and that several nonstructural proteins derived from the gene 1 polyprotein may participate in the formation and function of the viral replication complexes.",,"['van der Meer, Yvonne', 'Snijder, Eric J.', 'Dobbe, Jessika C.', 'Schleich, Sibylle', 'Denison, Mark R.', 'Spaan, Willy J. M.', 'Locker, Jacomine Krijnse']",,,,
,PMC,Targeted Recombination Demonstrates that the Spike Gene of Transmissible Gastroenteritis Coronavirus Is a Determinant  of Its Enteric Tropism and Virulence,,PMC104288,,,"Targeted recombination within the S (spike) gene of transmissible gastroenteritis coronavirus (TGEV) was promoted by passage of helper respiratory virus isolates in cells transfected with a TGEV-derived defective minigenome carrying the S gene from an enteric isolate. The minigenome was efficiently replicated in trans and packaged by the helper virus, leading to the formation of true recombinant and pseudorecombinant viruses containing the S proteins of both enteric and respiratory TGEV strains in their envelopes. The recombinants acquired an enteric tropism, and their analysis showed that they were generated by homologous recombination that implied a double crossover in the S gene resulting in replacement of most of the respiratory, attenuated strain S gene (nucleotides 96 to 3700) by the S gene of the enteric, virulent isolate. The recombinant virus was virulent and rapidly evolved in swine testis cells by the introduction of point mutations and in-phase codon deletions in a domain of the S gene (nucleotides 217 to 665) previously implicated in the tropism of TGEV. The helper virus, with an original respiratory tropism, was also found in the enteric tract, probably because pseudorecombinant viruses carrying the spike proteins from the respiratory strain and the enteric virus in their envelopes were formed. These results demonstrated that a change in the tropism and virulence of TGEV can be engineered by sequence changes in the S gene.",,"['Sánchez, Carlos M.', 'Izeta, Ander', 'Sánchez-Morgado, Jose M.', 'Alonso, Sara', 'Sola, Isabel', 'Balasch, Mónica', 'Plana-Durán, Juan', 'Enjuanes, Luis']",,,,
,PMC,Mapping of the Coronavirus Membrane Protein Domains Involved in Interaction with the Spike Protein,,PMC104271,,,"The coronavirus membrane (M) protein is the key player in virion assembly. One of its functions is to mediate the incorporation of the spikes into the viral envelope. Heterotypic interactions between M and the spike (S) protein can be demonstrated by coimmunoprecipitation and by immunofluorescence colocalization, after coexpression of their genes in eukaryotic cells. Using these assays in a mutagenetic approach, we have mapped the domains in the M protein that are involved in complex formation between M and S. It appeared that the 25-residue luminally exposed amino-terminal domain of the M protein is not important for M-S interaction. A 15-residue deletion, the insertion of a His tag, and replacement of the ectodomain by that of another coronavirus M protein did not affect the ability of the M protein to associate with the S protein. However, complex formation was sensitive to changes in the transmembrane domains of this triple-spanning protein. Deletion of either the first two or the last two transmembrane domains, known not to affect the topology of the protein, led to a considerable decrease in complex formation, but association was not completely abrogated. Various effects of changes in the part of the M protein that is located at the cytoplasmic face of the membrane were observed. Deletions of the extreme carboxy-terminal tail appeared not to interfere with M-S complex formation. However, deletions in the amphipathic domain severely affected M-S interaction. Interestingly, changes in the amino-terminal and extreme carboxy-terminal domains of M, which did not disrupt the interaction with S, are known to be fatal to the ability of the protein to engage in virus particle formation (C. A. M. de Haan, L. Kuo, P. S. Masters, H. Vennema, and P. J. M. Rottier, J. Virol. 72:6838–6850, 1998). Apparently, the structural requirements of the M protein for virus particle assembly differ from the requirements for the formation of M-S complexes.",,"['de Haan, Cornelis A. M.', 'Smeets, M.', 'Vernooij, F.', 'Vennema, H.', 'Rottier, P. J. M.']",,,,
,PMC,Inhibitory Activity of Constitutive Nitric Oxide on the Expression of Alpha/Beta Interferon Genes in Murine Peritoneal Macrophages,,PMC104258,,,"We investigated the role of the constitutive nitric oxide (NO) in the expression of interferon (IFN) genes in mouse peritoneal macrophages (PM). The treatment of PM with l-arginine-N(G)-amine (AA), a potent inhibitor of NO-producing enzymes, resulted in a marked accumulation of IFN-α4 mRNA and, to a minor extent, of IFN-β mRNA. In contrast, the expression of IFN-γ mRNA, as well as tumor necrosis factor alpha and interleukin-6 mRNA, was not affected. Furthermore, a remarkable increase in the expression of the IFN regulating factor 1 (IRF-1), but not of IRF-2, mRNA was detected in AA-treated PM. To investigate whether the AA-induced activation of the IFN system correlates with the production and antiviral activity of IFN, the extent of encephalomyocarditis virus (EMCV) replication was monitored in AA-treated PM with respect to control cultures. AA treatment strongly inhibited, in a dose-dependent manner, EMCV yields in PM. Likewise, similar results were obtained by the addition of the NO-scavenger carboxyphenyl-tetramethylimidazoline-oxyl-oxide. In addition, inhibition of NO synthesis by N(G)-mono-methyl-l-arginine in PM strongly decreased virus replication in coculture of PM and EMCV-infected L929 cells, whereas no antiviral effect was observed in L929 cells alone. Moreover, the AA-mediated antiviral activity was abrogated in the presence of antibody to IFN-α/β, whereas antibody to IFN-γ was completely ineffective. Taken together, these results indicate that low levels of NO, constitutively released by resting PM, negatively regulate the expression and activity of IFN-α/β in PM. We suggest that NO acts as a homeostatic agent in the regulation of IFN pathway expression in macrophages.",,"['Guillemard, Eric', 'Varano, Barbara', 'Belardelli, Filippo', 'Quero, A. M.', 'Gessani, Sandra']",,,,
,PMC,The associations of viral and mycoplasmal antibody titers with respiratory disease and weight gain in feedlot calves.,,PMC1539768,,,"Blood samples from 32 groups of calves (n = 700) were taken on arrival and after 28-35 days at the feedlot. Eleven groups were housed in feedlots in Ontario, and 21 groups in feedlots in Alberta. Serum antibody titers to bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), parainfluenza virus type 3 (PIV-3), infectious bovine rhinotracheitis virus (IBRV), Mycoplasma dispar and M. bovis, plus data on bovine corona virus (BCV) from a previous study were investigated for their association with the risk of bovine respiratory disease (BRD), and with 28-day weight change, both before and after controlling for titers to Pasteurella haemolytica and Haemophilus somnus. Exposure to IBRV and M. bovis was infrequent, and although exposure to PIV-3 was more common, none of these agents had important associations with BRD. Higher titers to BVDV, BRSV, and BCV on arrival were associated with reduced risks of BRD and increased weight gains. However, there was some variation in these relationships and higher arrival titers to BVDV and BRSV in a subset of the calves were associated with increased risks of BRD. Titer increases to BVDV were associated with a higher risk of BRD and lower weight gains. Titer increases to BRSV were not usually associated with the occurrence of BRD, but titer increases to BRSV in a subset of calves that were vaccinated against BRSV, on arrival, were associated with an elevated risk of BRD. Of all the agents studied, BVDV had the most consistent associations with elevated risk of BRD and lower weight gains. Higher BRSV arrival titers were related to lower risk of BRD and higher weight gains; in some instances titer increases to BRSV were associated with higher BRD risk. Higher titers to BCV on arrival were related to reduced risks of BRD. Practical ways of adequately preventing the negative effects of these agents are still needed.",,"['Martin, S W', 'Nagy, E', 'Armstrong, D', 'Rosendal, S']",,,,
,PMC,Influenza A among community-dwelling elderly persons in Leicestershire during winter 1993-4; cigarette smoking as a risk factor and the efficacy of influenza vaccination.,,PMC2810733,,,"In a prospective study of community-dwelling people 60-90 years of age, we examined the coverage of influenza vaccine during 1992-3 and 1993-4, the efficacy of vaccination in reducing serologically-confirmed clinical episodes of influenza A during 1993, and the effect of cigarette smoking. During 1992 and 1993, influenza vaccine was given to 106/215 (49%) and 120/204 (59%) people with risk conditions, and 84/225 (37%) and 103/235 (44%) without risk conditions. Influenza vaccination and general practitioner consultations during 1992 were independent predictors of vaccination in 1993, but current smoking was a negative predictor. Of 209 unimmunized people, 8/35 (23%) smokers had clinical influenza as compared with 11/174 (6%) non-smokers (OR 4.4, 95% CI 1.6 to 11.9). Of 371 non-smokers, 1/197 (0.5%) vaccinees had influenza as compared with 11/174 (6%) non-vaccinees (OR 0.075, 95% CI 0.587 to 0.009). No cases of influenza occurred among 21 current smokers who were vaccinated.",,"['Nicholson, K. G.', 'Kent, J.', 'Hammersley, V.']",,,,
,PMC,Specific Interaction between the Hepatitis C Virus NS5B RNA Polymerase and the 3′ End of the Viral RNA,,PMC112794,,,"Hepatitis C virus (HCV) NS5B protein is the viral RNA-dependent RNA polymerase capable of directing RNA synthesis. In this study, an electrophoretic mobility shift assay demonstrated the interaction between a partially purified recombinant NS5B protein and a 3′ viral genomic RNA with or without the conserved 98-nucleotide tail. The NS5B-RNA complexes were specifically competed away by the unlabeled homologous RNA but not by the viral 5′ noncoding region and very poorly by the 3′ conserved 98-nucleotide tail. A 3′ coding region with conserved stem-loop structures rather than the 3′ noncoding region of the HCV genome is critical for the specific binding of NS5B. Nevertheless, no direct interaction between the 3′ coding region and the HCV NS5A protein was detected. Furthermore, two independent RNA-binding domains (RBDs) of NS5B were identified, RBD1, from amino acid residues 83 to 194, and RBD2, from residues 196 to 298. Interestingly, the conserved motifs of RNA-dependent RNA polymerase for putative RNA binding (220-DxxxxD-225) and template/primer position (282-S/TGxxxTxxxNS/T-292) are present in the RBD2. Nevertheless, the RNA-binding activity of RBD2 was abolished when it was linked to the carboxy-terminal half of the NS5B. These results provide some clues to understanding the initiation of HCV replication.",,"['Cheng, Ju-Chien', 'Chang, Ming-Fu', 'Chang, Shin C.']",,,,
,PMC,The Putative Helicase of the Coronavirus Mouse Hepatitis Virus Is Processed from the Replicase Gene Polyprotein  and Localizes in Complexes That Are Active in Viral RNA Synthesis,,PMC112771,,,"The coronavirus mouse hepatitis virus (MHV) translates its replicase gene (gene 1) into two co-amino-terminal polyproteins, polyprotein 1a and polyprotein 1ab. The gene 1 polyproteins are processed by viral proteinases to yield at least 15 mature products, including a putative RNA helicase from polyprotein 1ab that is presumed to be involved in viral RNA synthesis. Antibodies directed against polypeptides encoded by open reading frame 1b were used to characterize the expression and processing of the MHV helicase and to define the relationship of helicase to the viral nucleocapsid protein (N) and to sites of viral RNA synthesis in MHV-infected cells. The antihelicase antibodies detected a 67-kDa protein in MHV-infected cells that was translated and processed throughout the virus life cycle. Processing of the 67-kDa helicase from polyprotein 1ab was abolished by E64d, a known inhibitor of the MHV 3C-like proteinase. When infected cells were probed for helicase by immunofluorescence laser confocal microscopy, the protein was detected in patterns that varied from punctate perinuclear complexes to large structures that occupied much of the cell cytoplasm. Dual-labeling studies of infected cells for helicase and bromo-UTP-labeled RNA demonstrated that the vast majority of helicase-containing complexes were active in viral RNA synthesis. Dual-labeling studies for helicase and the MHV N protein showed that the two proteins almost completely colocalized, indicating that N was associated with the helicase-containing complexes. This study demonstrates that the putative RNA helicase is closely associated with MHV RNA synthesis and suggests that complexes containing helicase, N, and new viral RNA are the viral replication complexes.",,"['Denison, Mark R.', 'Spaan, Willy J. M.', 'van der Meer, Yvonne', 'Gibson, C. Anne', 'Sims, Amy C.', 'Prentice, Erik', 'Lu, Xiao Tao']",,,,
,PMC,Identification of a Novel Structural Protein of Arteriviruses,,PMC112712,,,"Arteriviruses are positive-stranded RNA viruses with an efficiently organized, polycistronic genome. A short region between the replicase gene and open reading frame (ORF) 2 of the equine arteritis virus (EAV) genome was previously assumed to be untranslated. However, here we report that this segment of the EAV genome contains the 5′ part of a novel gene (ORF 2a) which is conserved in all arteriviruses. The 3′ part of EAV ORF 2a overlaps with the 5′ part of the former ORF 2 (now renamed ORF 2b), which encodes the G(S) glycoprotein. Both ORF 2a and ORF 2b appear to be expressed from mRNA 2, which thereby constitutes the first proven example of a bicistronic mRNA in arteriviruses. The 67-amino-acid protein encoded by EAV ORF 2a, which we have provisionally named the envelope (E) protein, is very hydrophobic and has a basic C terminus. An E protein-specific antiserum was raised and used to demonstrate the expression of the novel gene in EAV-infected cells. The EAV E protein proved to be very stable, did not form disulfide-linked oligomers, and was not N-glycosylated. Immunofluorescence and immunoelectron microscopy studies showed that the E protein associates with intracellular membranes both in EAV-infected cells and upon independent expression. An analysis of purified EAV particles revealed that the E protein is a structural protein. By using reverse genetics, we demonstrated that both the EAV E and G(S) proteins are essential for the production of infectious progeny virus.",,"['Snijder, Eric J.', 'van Tol, Hans', 'Pedersen, Ketil W.', 'Raamsman, Martin J. B.', 'de Vries, Antoine A. F.']",,,,
,PMC,Depletion of Blood-Borne Macrophages Does Not Reduce  Demyelination in Mice Infected with a  Neurotropic Coronavirus,,PMC112711,,,"Mice infected with the neurotropic coronavirus mouse hepatitis virus strain JHM (MHV-JHM) develop a chronic demyelinating disease with symptoms of hindlimb paralysis. Histological examination of the brains and spinal cords of these animals reveals the presence of large numbers of activated macrophages/microglia. In two other experimental models of demyelination, experimental allergic encephalomyelitis and Theiler’s murine encephalomyelitis virus-induced demyelination, depletion of hematogenous macrophages abrogates the demyelinating process. In both of these diseases, early events in the demyelinating process are inhibited by macrophage depletion. From these studies, it was not possible to determine whether infiltrating macrophages were required for late steps in the process, such as myelin removal. In this study, we show that when macrophages are depleted with either unmodified or mannosylated liposomes encapsulating dichloromethylene diphosphate, the amount of demyelination detected in MHV-infected mice is not affected. At a time when these cells were completely depleted from the liver, approximately equivalent numbers of macrophages were present in the spinal cords of control and drug-treated animals. These results suggest that blood-borne macrophages are not required for MHV-induced demyelination and also suggest that other cells, such as perivascular macrophages or microglia, perform the function of these cells in the presence of drug.",,"['Xue, Shurong', 'Sun, Ning', 'Van Rooijen, Nico', 'Perlman, Stanley']",,,,
,PMC,Protective immunity against murine hepatitis virus (MHV) induced by intranasal or subcutaneous administration of hybrids of tobacco mosaic virus that carries an MHV epitope,,PMC22137,,,"Hybrids of tobacco mosaic virus (TMV) were constructed with the use of fusion to the coat protein peptides of 10 or 15 amino acids, containing the 5B19 epitope from the spike protein of murine hepatitis virus (MHV) and giving rise to TMV-5B19 and TMV-5B19L, respectively. The TMV hybrids were propagated in tobacco plants, and the virus particles were purified. Immunogold labeling, with the use of the monoclonal MAb5B19 antibody, showed specific decoration of hybrid TMV particles, confirming the expression and display of the MHV epitope on the surface of the TMV. Mice were immunized with purified hybrid viruses after several regimens of immunization. Mice that received TMV-5B19L intranasally developed serum IgG and IgA specific for the 5B19 epitope and for the TMV coat protein. Hybrid TMV-5B19, administered by subcutaneous injections, elicited high titers of serum IgG that was specific for the 5B19 epitope and for coat protein, but IgA that was specific against 5B19 was not observed. Mice that were immunized with hybrid virus by subcutaneous or intranasal routes of administration survived challenge with a lethal dose (10 × LD(50)) of MHV strain JHM, whereas mice administered wild-type TMV died 10 d post challenge. Furthermore, there was a positive correlation between the dose of administered immunogen and protection against MHV infection. These studies show that TMV can be an effective vaccine delivery vehicle for parenteral and mucosal immunization and for protection from challenge with viral infection.",,"['Koo, Moses', 'Bendahmane, Mohammed', 'Lettieri, Gerard A.', 'Paoletti, Alyssa D.', 'Lane, Thomas E.', 'Fitchen, John H.', 'Buchmeier, Michael J.', 'Beachy, Roger N.']",,,,
,PMC,Development of an Antigen Spot Test for Detection  of Coronavirus in Bovine Fecal Samples,,PMC95724,,,"We have developed a rapid and sensitive microimmunodot blot assay, the antigen spot test (AST), for the detection of bovine coronavirus (BCV) antigen from neonatal calf fecal samples. The AST procedure can be completed in 3.5 h, whereas the previously reported immunodot blot assays require 10 to 12 h. Ninety-six samples can be tested per membrane, and 10 membranes (960 samples) may be processed by a single technologist in 1 working day. The effects of detergents, oxidizing chemicals, chaotropic agents, and enzyme substrates in improving the sensitivity and signal-to-noise ratio of the AST were studied. Finally, the sensitivity and specificity of AST for the detection of BCV antigen were compared to those of a sandwich enzyme-linked immunosorbant assay (ELISA) and a hemagglutination assay (HA). Of 347 field samples tested by all three methods, 94.2% were positive by AST, 91.4% were positive by ELISA, and 86.7% were positive by HA. The sensitivity of the AST was determined to be 100% compared to the results of the ELISA reference method. The specificity of the AST was 67%, which reflects a lower limit of detection of 10(4) viral particles per ml in a 10% fecal suspension.",,"['Gaber, Fathy', 'Kapil, Sanjay']",,,,
,PMC,Evaluation of Newly Developed Immunoperoxidase  Monolayer Assays for Detection of Antibodies against  Bovine  Herpesvirus 4,,PMC95706,,,"This study describes the evaluation of immunoperoxidase monolayer assays (IPMAs) for detection of antibodies against bovine herpesvirus 4 (BHV4) DN-599 or BHV4 LVR 140 in sera of cattle. We compared the quality of these IPMAs with the quality of a BHV4 indirect enzyme-linked immunosorbent assay (ELISA). In addition, a preliminary serological survey of BHV4 antibodies was carried out to estimate the seroprevalence of BHV4 in Dutch cattle at different ages. The specificities of both BHV4 IPMAs were 1.00. The geometrical mean titers (detection limit) of the BHV4 IPMAs were twice as high as that of the BHV4 indirect ELISA. In experimentally infected cattle, BHV4 antibodies were detectable by IPMAs 16 to 18 days postinfection, which was almost 2 weeks earlier than in the indirect ELISA. The reproducibility of the BHV4 DN-599 IPMA ((κ)D value, 0.92) and of the BHV4 LVR 140 IPMA ((κ)D value, 0.87) were good. For field sera the overall agreement between the BHV4 indirect ELISA and the two BHV4 IPMAs, DN-599 and LVR 140, was 95 and 96%, respectively. The serological-survey study showed that the estimated seroprevalence of BHV4 in Dutch cattle was 16 to 18% and that the percentage of BHV4-positive animals varied by age category (between 6 and 43%). In summary, the two BHV4 IPMA formats have several advantages that make IPMA a useful alternative to the BHV4 indirect ELISA for detecting BHV4 antibodies in cattle.",,"['Wellenberg, G. J.', 'van Rooij, E. M. A.', 'Maissan, J.', 'Van\n Oirschot, J. T.']",,,,
,PMC,Production of high titre disabled infectious single cycle (DISC) HSV from a microcarrier culture,http://dx.doi.org/10.1023/A:1008005200711,PMC3449936,,,Disabled Infectious Single Cycle (DISC) HSV-2 has been cultured in the complimentary cell line CR2 to provide high titre bulk material suitable for the purification of the virus as a live viral vaccine. CR2 cells are cultured on the microcarrier Cytodex-1 at 5 g l-1 in small scale (1 l) and larger scale (15 l) reactors. The cells are infected at an MOI of 0.01 pfu cell-1 and the culture harvested 60–72 h later. The infected cells are removed from the microcarriers by the addition of a hypotonic saline and the virus released by low-pressure disruption techniques. Virus titres achieved are compared to the standard roller bottle process. The resulting material is the starting point for the purification of the DISC-HSV virus.,,"['Zecchini, T.A.', 'Smith, R.J.']",,,,
,PMC,Insertion of a New Transcriptional Unit into the Genome of Mouse Hepatitis Virus,,PMC112680,,,"The subgenomic mRNAs of the coronavirus mouse hepatitis virus (MHV) are composed of a leader sequence, identical to the 5′ 70 nucleotides of the genome, joined at distant downstream sites to a stretch of sequence that is identical to the 3′ end of the genome. The points of fusion occur at intergenic sequences (IGSs), loci on the genome that contain a tract of sequence homologous to the 3′ end of the leader RNA. We have constructed a mutant of MHV-A59 containing an extra IGS inserted into the genome immediately downstream of the 3′-most gene, that encoding the nucleocapsid (N) protein. We show that in cells infected with the mutant, there is synthesis of an additional leader-containing subgenomic RNA of the predicted size. Our study demonstrates that (i) an IGS can be a sufficient cis-acting element to dictate MHV transcription, (ii) the relative efficiency of an IGS must be influenced by factors other than the nucleotides immediately adjacent to the 5′AAUCUAAAC3′ core consensus sequence or its position relative to the 3′ end of the genome, (iii) a downstream IGS can exert a polar attenuating effect on upstream IGSs, and (iv) unknown factors prevent the insertion of large exogenous elements between the N gene and the 3′ untranslated region of MHV. These results confirm and extend conclusions previously derived from the analysis of defective interfering RNAs.",,"['Hsue, Bilan', 'Masters, Paul S.']",,,,
,PMC,Colocalization and Membrane Association of Murine Hepatitis Virus Gene 1 Products and De Novo-Synthesized Viral RNA  in Infected Cells,,PMC112657,,,"Murine hepatitis virus (MHV) gene 1, the 22-kb polymerase (pol) gene, is first translated into a polyprotein and subsequently processed into multiple proteins by viral autoproteases. Genetic complementation analyses suggest that the majority of the gene 1 products are required for viral RNA synthesis. However, there is no physical evidence supporting the association of any of these products with viral RNA synthesis. We have now performed immunofluorescent-staining studies with four polyclonal antisera to localize various MHV-A59 gene 1 products in virus-infected cells. Immunoprecipitation experiments showed that these antisera detected proteins representing the two papain-like proteases and the 3C-like protease encoded by open reading frame (ORF) 1a, the putative polymerase (p100) and a p35 encoded by ORF 1b, and their precursors. De novo-synthesized viral RNA was labeled with bromouridine triphosphate in lysolecithin-permeabilized MHV-infected cells. Confocal microscopy revealed that all of the viral proteins detected by these antisera colocalized with newly synthesized viral RNA in the cytoplasm, particularly in the perinuclear region of infected cells. Several cysteine and serine protease inhibitors, i.e., E64d, leupeptin, and zinc chloride, inhibited viral RNA synthesis without affecting the localization of viral proteins, suggesting that the processing of the MHV gene 1 polyprotein is tightly associated with viral RNA synthesis. Dual labeling with antibodies specific for cytoplasmic membrane structures showed that MHV gene 1 products and RNA colocalized with the Golgi apparatus in HeLa cells. However, in murine 17CL-1 cells, the viral proteins and viral RNA did not colocalize with the Golgi apparatus but, instead, partially colocalized with the endoplasmic reticulum. Our results provide clear physical evidence that several MHV gene 1 products, including the proteases and the polymerase, are associated with the viral RNA replication-transcription machinery, which may localize to different membrane structures in different cell lines.",,"['Shi, Stephanie T.', 'Schiller, Jennifer J.', 'Kanjanahaluethai, Amornrat', 'Baker, Susan C.', 'Oh, Jong-Won', 'Lai, Michael M. C.']",,,,
,PMC,Differential Regulation of D(k) and K(k) Major Histocompatibility Complex Class I Proteins on the Cell Surface after  Infection of Murine Cells by Pseudorabies Virus,,PMC112635,,,"After pseudorabies virus (PRV) infection of murine L929 cells, the cell surface expression of major histocompatibility complex (MHC) class I proteins changes such that the total amount of MHC class I molecules remains relatively constant but the levels of the individual alleles D(k) and K(k) vary. This is an active process involving at least three PRV gene products that act in an allele-specific manner such that cell surface expression of MHC class I D(k) is decreased and that of K(k) is increased. Our results indicate that an early gene product mediates the overall reduction in D(k) protein and a late gene product which is mutant in the attenuated PRV strain Bartha mediates the increase in K(k) protein. We provide additional evidence for a third gene product involved in the regulation of the synthesis of both the D(k) and K(k) proteins. In addition, we show that the early decrease in the D(k) protein is not due to a block in synthesis or processing of the complex through the secretory system.",,"['Sparks-Thissen, R. L.', 'Enquist, L. W.']",,,,
,PMC,The Versatility of Paramyxovirus RNA Polymerase Stuttering,,PMC112614,,,"Paramyxoviruses cotranscriptionally edit their P gene mRNAs by expanding the number of Gs of a conserved A(n)G(n) run. Different viruses insert different distributions of guanylates, e.g., Sendai virus inserts a single G, whereas parainfluenza virus type 3 inserts one to six Gs. The sequences conserved at the editing site, as well as the experimental evidence, suggest that the insertions occur by a stuttering process, i.e., by pseudotemplated transcription. The number of times the polymerase “stutters” at the editing site before continuing strictly templated elongation is directed by a cis-acting sequence found upstream of the insertions. We have examined the stuttering process during natural virus infections by constructing recombinant Sendai viruses with mutations in their cis-acting sequences. We found that the template stutter site is precisely determined (C(1052)) and that a relatively short region (∼6 nucleotides) just upstream of the A(n)G(n) run can modulate the overall frequency of mRNA editing as well as the distribution of the nucleotide insertions. The positions more proximal to the 5′ A(n)G(n) run are the most important in this respect. We also provide evidence that the stability of the mRNA/template hybrid plays a determining role in the overall frequency and range of mRNA editing. When the template U run is extended all the way to the stutter site, adenylates rather than guanylates are added at the editing site and their distribution begins to resemble the polyadenylation associated with mRNA 3′ end formation by the viral polymerase. Our data suggest how paramyxovirus mRNA editing and polyadenylation are related mechanistically and how editing sites may have evolved from poly(A)-termination sites or vice versa.",,"['Hausmann, Stéphane', 'Garcin, Dominique', 'Delenda, Christophe', 'Kolakofsky, Daniel']",,,,
,PMC,Characterization of an Equine Arteritis Virus Replicase Mutant Defective in Subgenomic mRNA Synthesis,,PMC112582,,,"Equine arteritis virus (EAV) is a positive-stranded RNA virus that synthesizes a 5′- and 3′-coterminal nested set of six subgenomic mRNAs. These mRNAs all contain a common leader sequence which is derived from the 5′ end of the genome. Subgenomic mRNA transcription and genome replication are directed by the viral replicase, which is expressed in the form of two polyproteins and subsequently processed into smaller nonstructural proteins (nsps). During the recent construction of an EAV infectious cDNA clone (pEAV030 [L. C. van Dinten, J. A. den Boon, A. L. M. Wassenaar, W. J. M. Spaan, and E. J. Snijder, Proc. Natl. Acad. Sci. USA 94:991–996, 1997]), a mutant cDNA clone (pEAV030F) which carries a single replicase point mutation was obtained. This substitution (Ser-2429→Pro) is located in the nsp10 subunit and renders the EAV030F virus deficient in subgenomic mRNA synthesis. To obtain more insight into the role of nsp10 in transcription and the nature of the transcriptional defect, we have now analyzed the EAV030F mutant in considerable detail. The Ser-2429→Pro mutation does not affect the proteolytic processing of the replicase but apparently affects the function of nsp10 in transcription. Furthermore, our study showed that EAV030F still produces subgenomic positive and negative strands, albeit at a very low level. Both subgenomic positive-strand synthesis and negative-strand synthesis are equally affected by the Ser-2429→Pro mutation, suggesting that nsp10 plays an important role in an early step of EAV mRNA transcription.",,"['van Marle, Guido', 'van Dinten, Leonie C.', 'Spaan, Willy J. M.', 'Luytjes, Willem', 'Snijder, Eric J.']",,,,
,PMC,Pigs with highly prevalent antibodies to human coronavirus and swine haemagglutinating encephalomyelitis virus in the Tohoku District of Japan.,,PMC2809651,,,"From 1985 to 1988, a total of 2496 swine sera from 60 farms in the Tohoku District of the Honshu Island of Japan were examined for antibodies to swine haemagglutinating encephalomyelitis virus (HEV), human coronavirus (HCV) and bovine coronavirus (BCV) by haemagglutination-inhibition (HI) test. Antibodies to HEV 67N strain and HCV OC43 strain were highly prevalent with positivity rates of 82.1 and 91.4%, respectively, while seropositivity rate to BCV Kakegawa strain was 44.2%. No clinical signs of HEV infection were noticed in any farms including farms with relatively high seropositivity. The results suggested that HCV or antigenitically related virus(es) as well as HEV might be perpetuated in swine in the Tohoku District.",,"['Hirano, N.', 'Suzuki, Y.', 'Haga, S.']",,,,
,PMC,Typing of Bovine Viral Diarrhea Viruses Directly from Blood of Persistently Infected Cattle by Multiplex PCR,,PMC85017,,,"A nested multiplex PCR was developed for genotyping of bovine viral diarrhea viruses (BVDVs). The assay could detect as little as 3 50% tissue culture infective doses of BVDV per ml and typed 42 out of 42 cell culture isolates. BVDV was also successfully typed, with or without RNA extraction, from all 27 whole-blood samples examined from 22 carriers or probable carriers and 5 experimentally infected cattle.",,"['Gilbert, S. A.', 'Burton, K. M.', 'Prins, S. E.', 'Deregt, D.']",,,,
,PMC,Evaluation of the ImmunoCardSTAT! Rotavirus Assay for Detection of Group A Rotavirus in Fecal Specimens,,PMC85001,,,"Rapid detection of group A rotavirus was performed by using ImmunoCardStat! Rotavirus (ICS-RV) (which uses immunogold-based, horizontal-flow membrane technology), two commercial enzyme immunoassays (Premier Rotaclone and TestPack Rotavirus), and electron microscopy. A total of 249 stool specimens collected from children with gastroenteritis between February and April 1997 were tested. After resolution of 19 of the 22 discordant results by reverse transcription-PCR for group A rotavirus, ICS-RV detected 125 positives while Rotaclone and TestPack detected 127 and 129 positives, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value were 94.0, 100, 100, and 93.4% for ICS-RV; 95.5, 100, 100, and 95.0% for Rotaclone; and 97.0, 96.5, 97.0, and 96.5% for TestPack. ICS-RV was sensitive and specific and was relatively simple to perform and interpret.",,"['Dennehy, Penelope H.', 'Hartin, Michele', 'Nelson, Sara M.', 'Reising, Shirley F.']",,,,
,PMC,"Incidence of Upper Respiratory Tract Mycoplasma pneumoniae Infections among Outpatients in Rhône-Alpes, France,  during Five Successive Winter Periods",,PMC84933,,,"In this prospective study, nasal swab samples from patients with acute respiratory infections were evaluated for the presence of Mycoplasma pneumoniae. This PCR-plus-hybridization-based detection was associated with the detection of other viral agents. During the five winter surveillance periods, 3,897 samples were collected by 75 medical practitioners participating in the Groupe Régional d’Observation de la Grippe surveillance network in Rhône-Alpes (France). M. pneumoniae was detected in 283 samples (7.3%); its rate of detection ranged from 10.1 to 2.0% over the five periods, and it was the second most frequently isolated pathogen during the survey, after influenza A. Three high-prevalence winters were observed, yielding an early winter peak of M. pneumoniae infection which was observed in all age groups. No statistically significant difference was detected between rates of infections in the different age groups, but M. pneumoniae infection was significantly related to lower respiratory tract infection during periods of high prevalence. This study defined the frequency of M. pneumoniae detection from nasal swab specimens in patients with acute respiratory infections, confirming its high prevalence and the presence of large outbreaks due to this pathogen.",,"['Layani-Milon, Marie-Paule', 'Gras, Isabelle', 'Valette, Martine', 'Luciani, Jacques', 'Stagnara, Jean', 'Aymard, Michèle', 'Lina, Bruno']",,,,
,PMC,Role of the Individual Interferon Systems and Specific Immunity in Mice in Controlling Systemic Dissemination of Attenuated Pseudorabies Virus Infection,,PMC112517,,,"The importance of each of the two interferon (IFN) systems in impeding herpesvirus replication and in stimulating virus-specific lymphocytes to control an acute systemic infection is not completely understood. To further our knowledge, pseudorabies virus, attenuated by deletion of the glycoprotein E gene to impair its neurovirulence and by deletion of the thymidine kinase gene (gE(−)TK(−)PRV), was used to infect wild-type 129Sv/Ev and congenic mice with immune system-associated genetic deficiencies. Mice with mature B and T lymphocytes but lacking either one or both functional receptors for members of each of the two IFN families were infected with gE(−)TK(−)PRV. At 3 and 7 but not 14 days after infection, replicating gE(−)TK(−)PRV could be isolated only from livers or spleens of mice lacking the receptors for both IFN families, and these mice survived the infection. Therefore, functional IFN receptors were not required to induce a protective immune response against an acute infection with gE(−)TK(−)PRV. Furthermore, PRV-specific antibodies of all immunoglobulin G isotypes were produced in these mice. Mice without mature B and T lymphocytes and lacking either one or both functional receptors for members of each of the two IFN families were also infected with gE(−)TK(−)PRV. Three days after infection, replicating virus could be isolated only from mice lacking both mature B and T lymphocytes and functional IFN receptors, and these mice were not able to clear the virus. We present evidence that mice with an intact gamma IFN system but without mature B and T cells were able to prevent systemic dissemination of gE(−)TK(−)PRV.",,"['Grob, Philipp', 'Schijns, Virgil E. C. J.', 'van den Broek, Maries F.', 'Cox, Silvie P. J.', 'Ackermann, Mathias', 'Suter, Mark']",,,,
,PMC,The Hemagglutinin-Esterase of Mouse Hepatitis Virus Strain S Is a Sialate-4-O-Acetylesterase,,PMC112514,,,"By comparative analysis of the hemagglutinin-esterase (HE) protein of mouse hepatitis virus strain S (MHV-S) and the HE protein of influenza C virus, we found major differences in substrate specificities. In striking contrast to the influenza C virus enzyme, the MHV-S esterase was unable to release acetate from bovine submandibulary gland mucin. Furthermore, MHV-S could not remove influenza C virus receptors from erythrocytes. Analysis with free sialic acid derivatives revealed that the MHV-S HE protein specifically de-O-acetylates 5-N-acetyl-4-O-acetyl sialic acid (Neu4,5Ac(2)) but not 5-N-acetyl-9-O-acetyl sialic acid (Neu5,9Ac(2)), which is the major substrate for esterases of influenza C virus and bovine coronaviruses. In addition, the MHV-S esterase converted glycosidically bound Neu4,5Ac(2) of guinea pig serum glycoproteins to Neu5Ac. By expression of the MHV esterase with recombinant vaccinia virus and incubation with guinea pig serum, we demonstrated that the viral HE possesses sialate-4-O-acetylesterase activity. In addition to observed enzymatic activity, MHV-S exhibited affinity to guinea pig and horse serum glycoproteins. Binding required sialate-4-O-acetyl groups and was abolished by chemical de-O-acetylation. Since Neu4,5Ac(2) has not been identified in mice, the nature of potential substrates and/or secondary receptors for MHV-S in the natural host remains to be determined. The esterase of MHV-S is the first example of a viral enzyme with high specificity and affinity toward 4-O-acetylated sialic acids.",,"['Regl, Gerhard', 'Kaser, Alexandra', 'Iwersen, Matthias', 'Schmid, Hiltrud', 'Kohla, Guido', 'Strobl, Birgit', 'Vilas, Ulrike', 'Schauer, Roland', 'Vlasak, Reinhard']",,,,
,PMC,"Production, Characterization, and Uses of  Monoclonal Antibodies against Recombinant Nucleoprotein of  Elk Coronavirus",,PMC103720,,,"This is the first report of the production of monoclonal antibodies against elk coronavirus. The nucleoprotein gene of elk coronavirus was amplified by PCR and was cloned and expressed in a prokaryotic expression vector. Recombinant nucleocapsid protein was used to immunize mice for the production of hybridomas. Twelve hybridomas that produced monoclonal antibodies against the nucleocapsid protein of elk coronavirus were selected by an indirect fluorescent-antibody test, an enzyme-linked immunosorbent assay, and a Western blot assay. Ten of the monoclonal antibodies were of the immunoglobulin G1 (IgG1) isotype, one was IgG2a, and one was IgM. All had kappa light chains. By immunohistochemistry four monoclonal antibodies detected bovine coronavirus and elk coronavirus in formalin-fixed intestinal tissues. Antinucleoprotein monoclonal antibodies were found to be better at ruminant coronavirus detection than the anti-spike protein monoclonal antibodies. Because nucleoprotein is a more abundant antigen than spike protein in infected cells, this was not an unexpected finding.",,"['Daginakatte, Girish C.', 'Chard-Bergstrom, Cindy', 'Andrews, Gordon A.', 'Kapil, Sanjay']",,,,
,PMC,Identification of Putative Programmed −1 Ribosomal Frameshift Signals in Large DNA Databases,,PMC310776,,,"The cis-acting elements that promote efficient ribosomal frameshifting in the −1 (5′) direction have been well characterized in several viral systems. Results from many studies have convincingly demonstrated that the basic molecular mechanisms governing programmed −1 ribosomal frameshifting are almost identical from yeast to humans. We are interested in testing the hypothesis that programmed −1 ribosomal frameshifting can be used to control cellular gene expression. Toward this end, a computer program was designed to search large DNA databases for consensus −1 ribosomal frameshift signals. The results demonstrated that consensus programmed −1 ribosomal frameshift signals can be identified in a substantial number of chromosomally encoded mRNAs and that they occur with frequencies from two- to sixfold greater than random in all of the databases searched. A preliminary survey of the databases resulting from the computer searches found that consensus frameshift signals are present in at least 21 homologous genes from different species, 2 of which are nearly identical, suggesting evolutionary conservation of function. We show that four previously described missense alleles of genes that are linked to human diseases would disrupt putative programmed −1 ribosomal frameshift signals, suggesting that the frameshift signal may be involved in the normal expression of these genes. We also demonstrate that signals found in the yeast RAS1 and the human CCR5 genes were able to promote significant levels of programmed −1 ribosomal frameshifting. The significance of these frameshifting signals in controlling gene expression is not known, however.",,"['Hammell, Amy B.', 'Taylor, Ronald C.', 'Peltz, Stuart W.', 'Dinman, Jonathan D.']",,,,
,PMC,Multicenter Quality Assessment of PCR Methods for  Detection of Enteroviruses,,PMC84788,,,"We conducted a multicenter evaluation of commercial and in-house PCR methods for the detection of enteroviruses. Three coded panels of test and control RNA samples, artificial clinical specimens, and representative enterovirus serotypes were used to assess amplification methods, RNA extraction methods, and reactivities with different enterovirus serotypes. Despite several differences between PCR methods, there was good agreement, although some variation in sensitivity was observed. Most PCR methods were able to detect enterovirus RNA derived from 0.01 50% tissue culture infective dose (TCID(50)) and were able to detect at least 1 TCID(50) of enterovirus in cerebrospinal fluid, stool, or throat swab specimens. Most were also able to detect a wide range of enterovirus serotypes, although serotypic identification was not possible. Some laboratories experienced false-positive results due to PCR contamination, which appeared to result mainly from cross-contamination of specimens during RNA extraction. Provided that this problem is overcome, these PCR methods will prove to be a sensitive and rapid alternative to cell culture for the diagnosis of enterovirus infection.",,"['Muir, Peter', 'Ras, Albert', 'Klapper, Paul E.', 'Cleator, Graham M.', 'Korn, Klaus', 'Aepinus, Christian', 'Fomsgaard, Anders', 'Palmer, Pierre', 'Samuelsson, Agneta', 'Tenorio, Antonio', 'Weissbrich, Benedikt', 'van Loon, A. M.']",,,,
,PMC,Identification of a Coronavirus Hemagglutinin-Esterase with a Substrate Specificity Different from Those of Influenza C  Virus and Bovine Coronavirus,,PMC104150,,,"We have characterized the hemagglutinin-esterase (HE) of puffinosis virus (PV), a coronavirus closely related to mouse hepatitis virus (MHV). Analysis of the cloned gene revealed approximately 85% sequence identity to HE proteins of MHV and approximately 60% identity to the corresponding esterase of bovine coronavirus. The HE protein exhibited acetylesterase activity with synthetic substrates p-nitrophenyl acetate, α-naphthyl acetate, and 4-methylumbelliferyl acetate. In contrast to other viral esterases, no activity was detectable with natural substrates containing 9-O-acetylated sialic acids. Furthermore, PV esterase was unable to remove influenza C virus receptors from human erythrocytes, indicating a substrate specificity different from HEs of influenza C virus and bovine coronavirus. Solid-phase binding assays revealed that purified PV was unable to bind to sialic acid-containing glycoconjugates like bovine submaxillary mucin, mouse α(1) macroglobulin or bovine brain extract. Because of the close relationship to MHV, possible implications on the substrate specificity of MHV esterases are suggested.",,"['Klausegger, Alfred', 'Strobl, Birgit', 'Regl, Gerhard', 'Kaser, Alexandra', 'Luytjes, Willem', 'Vlasak, Reinhard']",,,,
,PMC,Role of Rubella Virus Glycoprotein Domains in Assembly of Virus-Like Particles,,PMC104124,,,"Rubella virus is a small enveloped positive-strand RNA virus that assembles on intracellular membranes in a variety of cell types. The virus structural proteins contain all of the information necessary to mediate the assembly of virus-like particles in the Golgi complex. We have recently identified intracellular retention signals within the two viral envelope glycoproteins. E2 contains a Golgi retention signal in its transmembrane domain, whereas a signal for retention in the endoplasmic reticulum has been localized to the transmembrane and cytoplasmic domains of E1 (T. C. Hobman, L. Woodward, and M. G. Farquhar, Mol. Biol. Cell 6:7–20, 1995; T. C. Hobman, H. F. Lemon, and K. Jewell, J. Virol. 71:7670–7680, 1997). In the present study, we have analyzed the role of these retention signals in the assembly of rubella virus-like particles. Deletion or replacement of these domains with analogous regions from other type I membrane glycoproteins resulted in failure of rubella virus-like particles to be secreted from transfected cells. The E1 transmembrane and cytoplasmic domains were not required for targeting of the structural proteins to the Golgi complex and, surprisingly, assembly and budding of virus particles into the lumen of this organelle; however, the resultant particles were not secreted. In contrast, replacement or alteration of the E2 transmembrane or cytoplasmic domain, respectively, abrogated the targeting of the structural proteins to the budding site, and consequently, no virion formation was observed. These results indicate that the transmembrane and cytoplasmic domains of E2 and E1 are required for early and late steps respectively in the viral assembly pathway and that rubella virus morphogenesis is very different from that of the structurally similar alphaviruses.",,"['Garbutt, Mike', 'Law, Lok Man J.', 'Chan, Honey', 'Hobman, Tom C.']",,,,
,PMC,Long-distance RNA-RNA interactions and conserved sequence elements affect potato virus X plus-strand RNA accumulation.,,PMC1369791,,,"Conserved octanucleotide sequences located upstream of two major potato virus X (PVX) subgenomic RNAs (sgRNAs), as well as elements in the 5' end of the genome, affect accumulation of sgRNA. To determine if complementarity between these sequences is important for PVX RNA accumulation, we analyzed the effects of mutations within these elements and compensatory mutations in a tobacco protoplast system and in plants. Mutations in the 5' nontranslated region (NTR mutants) that reduced complementarity resulted in lower genomic RNA (gRNA) and sgRNA levels, whereas mutations to the octanucleotide elements affected only the corresponding sgRNA levels. However, for both the NTR and octanucleotide mutants, the extent of reductions in RNA levels did not directly correlate with the degree of complementarity, suggesting that the sequences of these elements are also important. Mutants containing changes in the NTR and compensatory changes in one of the octanucleotide elements restored levels of gRNA and the other sgRNA species with an unaltered octanucleotide element to those of wild-type. Although compensatory changes significantly increased levels of the sgRNA species with the modified octanucleotide element, levels were not restored to those of wild-type. Our data indicate that long distance RNA-RNA interactions and the sequences of the interacting elements are required for PVX plus-strand RNA accumulation.",,"['Kim, K H', 'Hemenway, C L']",,,,
,PMC,An approximation of loop free energy values of RNA H-pseudoknots.,,PMC1369787,,,A set of free energy values is suggested for RNA H-pseudoknot loops. The parameters are adjusted to be consistent with the theory of polymer thermodynamics and known data on pseudoknots. The values can be used for estimates of pseudoknot stabilities and computer predictions of RNA structures.,,"['Gultyaev, A P', 'van Batenburg, F H', 'Pleij, C W']",,,,
,PMC,Mutagenic Analysis of the 3′ cis-Acting Elements  of the Rubella Virus Genome,,PMC104103,,,"Thermodynamically predicted secondary structure analysis of the 3′-terminal 305 nucleotides (nt) of the rubella virus (RUB) genome, a region conserved in all RUB defective interfering RNAs, revealed four stem-loop (SL) structures; SL1 and SL2 are both located in the E1 coding region, while SL3 and SL4 are within the 59-nt 3′ untranslated region (UTR) preceding the poly(A) tract. SL2 is a structure shown to interact with human calreticulin (CAL), an autoantigen potentially involved in RUB RNA replication and pathogenesis. RNase mapping indicated that SL2 and SL3 are in equilibrium between two conformations, in the second of which the previously proposed CAL binding site in SL2, a U-U bulge, is not formed. Site-directed mutagenesis of the 3′ UTR with a RUB infectious clone, Robo302, revealed that most of the 3′ UTR is required for viral viability except for the 3′-terminal 5 nt and the poly(A) tract, although poly(A) was rapidly regenerated during subsequent replication. Maintenance of the overall SL3 structure, the 11-nt single-stranded sequence between SL3 and SL4, and the sequences forming SL4 were all important for viral viability. Studies on the interaction between host factors and the 3′ UTR showed the formation of three RNA-protein complexes by gel mobility shift assay, and UV-induced cross-linking detected six host protein species, with molecular masses of 120, 80, 66, 55, 48, and 36 kDa, interacting with the 3′ UTR. Site-directed mutagenesis of SL2 by nucleotide substitutions showed that maintenance of SL2 stem rather than the U-U bulge was critical in CAL binding since mutants having the U-U bulge base paired had a similar binding activity for CAL as the native structure whereas mutants having the SL2 stem destabilized had much lower binding activity. However, all of these mutations gave rise to viable viruses when introduced into Robo302, indicating that binding of CAL to SL2 is independent of viral viability.",,"['Chen, Min-Hsin', 'Frey, Teryl K.']",,,,
,PMC,Acute and Persistent Infection of Human Neural Cell Lines by Human Coronavirus OC43,,PMC104098,,,"Human coronaviruses (HuCV) are recognized respiratory pathogens. Data accumulated by different laboratories suggest their neurotropic potential. For example, primary cultures of human astrocytes and microglia were shown to be susceptible to an infection by the OC43 strain of HuCV (A. Bonavia, N. Arbour, V. W. Yong, and P. J. Talbot, J. Virol. 71:800–806, 1997). We speculate that the neurotropism of HuCV will lead to persistence within the central nervous system, as was observed for murine coronaviruses. As a first step in the verification of our hypothesis, we have characterized the susceptibility of various human neural cell lines to infection by HuCV-OC43. Viral antigen, infectious virus progeny, and viral RNA were monitored during both acute and persistent infections. The astrocytoma cell lines U-87 MG, U-373 MG, and GL-15, as well as neuroblastoma SK-N-SH, neuroglioma H4, oligodendrocytic MO3.13, and the CHME-5 immortalized fetal microglial cell lines, were all susceptible to an acute infection by HuCV-OC43. Viral antigen and RNA and release of infectious virions were observed during persistent HuCV-OC43 infections (∼130 days of culture) of U-87 MG, U-373 MG, MO3.13, and H4 cell lines. Nucleotide sequences of RNA encoding the putatively hypervariable viral S1 gene fragment obtained after 130 days of culture were compared to that of initial virus input. Point mutations leading to amino acid changes were observed in all persistently infected cell lines. Moreover, an in-frame deletion was also observed in persistently infected H4 cells. Some point mutations were observed in some molecular clones but not all, suggesting evolution of the viral population and the emergence of viral quasispecies during persistent infection of H4, U-87 MG, and MO3.13 cell lines. These results are consistent with the potential persistence of HuCV-OC43 in cells of the human nervous system, accompanied by the production of infectious virions and molecular variation of viral genomic RNA.",,"['Arbour, Nathalie', 'Côté, Geneviève', 'Lachance, Claude', 'Tardieu, Marc', 'Cashman, Neil R.', 'Talbot, Pierre J.']",,,,
,PMC,Persistent Infection of Human Oligodendrocytic and Neuroglial Cell Lines by Human Coronavirus 229E,,PMC104097,,,"Human coronaviruses (HuCV) cause common colds. Previous reports suggest that these infectious agents may be neurotropic in humans, as they are for some mammals. With the long-term aim of providing experimental evidence for the neurotropism of HuCV and the establishment of persistent infections in the nervous system, we have evaluated the susceptibility of various human neural cell lines to acute and persistent infection by HuCV-229E. Viral antigen, infectious virus progeny and viral RNA were monitored during both acute and persistent infections. The astrocytoma cell lines U-87 MG, U-373 MG, and GL-15, as well as neuroblastoma SK-N-SH, neuroglioma H4, and oligodendrocytic MO3.13 cell lines, were all susceptible to an acute infection by HuCV-229E. The CHME-5 immortalized fetal microglial cell line was not susceptible to infection by this virus. The MO3.13 and H4 cell lines also sustained a persistent viral infection, as monitored by detection of viral antigen and infectious virus progeny. Sequencing of the S1 gene from viral RNA after ∼130 days of infection showed two point mutations, suggesting amino acid changes during persistent infection of MO3.13 cells but none for H4 cells. Thus, persistent in vitro infection did not generate important changes in the S1 portion of the viral spike protein, which was shown for murine coronaviruses to bear hypervariable domains and to interact with cellular receptor. These results are consistent with the potential persistence of HuCV-229E in cells of the human nervous system, such as oligodendrocytes and possibly neurons, and the virus’s apparent genomic stability.",,"['Arbour, Nathalie', 'Ekandé, Sophie', 'Côté, Geneviève', 'Lachance, Claude', 'Chagnon, Fanny', 'Tardieu, Marc', 'Cashman, Neil R.', 'Talbot, Pierre J.']",,,,
,PMC,"Production and Characterization of a Soluble, Active Form of Tva,  the Subgroup A Avian Sarcoma and Leukosis Virus Receptor",,PMC104065,,,"The receptor for the subgroup A avian sarcoma and leukosis viruses [ASLV(A)] is the cellular glycoprotein Tva. A soluble form of Tva, sTva, was produced and purified with a baculovirus expression system. Using this system, 7 to 10 mg of purified sTva per liter of cultured Sf9 cells was obtained. Characterization of the carbohydrate modification of sTva revealed that the three N glycosylation sites in sTva were differentially utilized; however, the O glycosylation common to Tva produced in mammalian and avian cells was not observed. Purified sTva demonstrates significant biological activity, specifically blocking infection of avian cells by ASLV(A) with a 90% inhibitory concentration of ∼25 pM. A quantitative enzyme-linked immunosorbent assay, developed to assess the binding of sTva to ASLV envelope glycoprotein, demonstrates that sTva has a high affinity for EnvA, with an apparent dissociation constant of approximately 0.3 nM. Once they are bound, a very stable complex is formed between EnvA and sTva, with an estimated complex half-life of 6 h. The soluble receptor protein described here represents a valuable tool for analysis of the receptor-envelope glycoprotein interaction and for structural analysis of Tva.",,"['Balliet, John W.', 'Berson, Joanne', 'D’Cruz, Celina M.', 'Huang, Julie', 'Crane, Joanne', 'Gilbert, Joanna M.', 'Bates, Paul']",,,,
,PMC,Primary and Secondary Structural Elements Required for Synthesis  of Barley Yellow Dwarf Virus Subgenomic RNA1,,PMC104045,,,"Barley yellow dwarf luteovirus (BYDV) generates three 3′-coterminal subgenomic RNAs (sgRNAs) in infected cells. The promoter of sgRNA1 is a putative hot spot for RNA recombination in luteovirus evolution. The sgRNA1 transcription start site was mapped previously to either nucleotide 2670 or nucleotide 2769 of BYDV genomic RNA (gRNA) in two independent studies. Our data support the former initiation site. The boundaries of the sgRNA1 promoter map between nucleotides 2595 and 2692 on genomic RNA. Computer prediction, phylogenetic comparison, and structural probing revealed two stem-loops (SL1 and SL2) in the sgRNA1 promoter region on the negative strand. Promoter function was analyzed by inoculating protoplasts with a full-length infectious clone of the BYDV genome containing mutations in the sgRNA promoter. Because the promoter is located in an essential coding region of the replicase gene, we duplicated it in a nonessential part of the genome from which a new sgRNA was expressed. Mutational analysis revealed that secondary structure, but not the nucleotide sequence, was important at the base of SL1. Regions with both RNA primary and secondary structural features that contributed to transcription initiation were found at the top of SL1. Primary sequence, but not the secondary structure, was required in SL2, which includes the initiation site. Disruption of base pairing near the sgRNA1 start site increased the level of transcription three- to fourfold. We propose that both primary and secondary structures of the sgRNA1 promoter of BYDV play unique roles in sgRNA1 promoter recognition and transcription initiation.",,"['Koev, Gennadiy', 'Mohan, B. R.', 'Miller, W. Allen']",,,,
,PMC,Expression of Murine Coronavirus Recombinant Papain-Like Proteinase: Efficient Cleavage Is Dependent on the Lengths  of both the Substrate and the Proteinase Polypeptides,,PMC104021,,,"Proteolytic processing of the replicase gene product of mouse hepatitis virus (MHV) is essential for viral replication. In MHV strain A59 (MHV-A59), the replicase gene encodes two predicted papain-like proteinase (PLP) domains, PLP-1 and PLP-2. Previous work using viral polypeptide substrates synthesized by in vitro transcription and translation from the replicase gene demonstrated both cis and trans cleavage activities for PLP-1. We have cloned and overexpressed the PLP-1 domain in Escherichia coli by using a T7 RNA polymerase promoter system or as a maltose-binding protein (MBP) fusion protein. With both overexpression systems, the recombinant PLP-1 exhibited trans cleavage activity when incubated with in vitro-synthesized viral polypeptide substrates. Subsequent characterization of the recombinant PLP-1 revealed that in vitro trans cleavage is more efficient at 22°C than at higher temperatures. Using substrates of increasing lengths, we observed efficient cleavage by PLP-1 requires a substrate greater than 69 kDa. In addition, when PLP-1 was expressed as a polypeptide that included additional viral sequences at the carboxyl terminus of the predicted PLP-1 domain, a fivefold increase in proteolytic activity was observed. The data presented here support previous data suggesting that in vitro and in vivo cleavage of the ORF 1a polyprotein by PLP-1 can occur in both in cis and in trans. In contrast to the cleavage activity demonstrated for PLP-1, no in vitro cleavage in cis or in trans could be detected with PLP-2 expressed either as a polypeptide, including flanking viral sequences, or as an MBP fusion enzyme.",,"['Teng, Henry', 'Piñón, Josefina D.', 'Weiss, Susan R.']",,,,
,PMC,The Transmembrane Domain of Hepatitis C Virus Glycoprotein E1 Is a Signal for Static Retention in the Endoplasmic Reticulum,,PMC104019,,,"Hepatitis C virus (HCV) glycoproteins E1 and E2 assemble to form a noncovalent heterodimer which, in the cell, accumulates in the endoplasmic reticulum (ER). Contrary to what is observed for proteins with a KDEL or a KKXX ER-targeting signal, the ER localization of the HCV glycoprotein complex is due to a static retention in this compartment rather than to its retrieval from the cis-Golgi region. A static retention in the ER is also observed when E2 is expressed in the absence of E1 or for a chimeric protein containing the ectodomain of CD4 in fusion with the transmembrane domain (TMD) of E2. Although they do not exclude the presence of an intracellular localization signal in E1, these data do suggest that the TMD of E2 is an ER retention signal for HCV glycoprotein complex. In this study chimeric proteins containing the ectodomain of CD4 or CD8 fused to the C-terminal hydrophobic sequence of E1 were shown to be localized in the ER, indicating that the TMD of E1 is also a signal for ER localization. In addition, these chimeric proteins were not processed by Golgi enzymes, indicating that the TMD of E1 is responsible for true retention in the ER, without recycling through the Golgi apparatus. Together, these data suggest that at least two signals (TMDs of E1 and E2) are involved in ER retention of the HCV glycoprotein complex.",,"['Cocquerel, Laurence', 'Duvet, Sandrine', 'Meunier, Jean-Christophe', 'Pillez, André', 'Cacan, René', 'Wychowski, Czeslaw', 'Dubuisson, Jean']",,,,
,PMC,Viral movement proteins as probes for intracellular and intercellular trafficking in plants,,PMC144200,,,,,"['Lazarowitz, SG', 'Beachy, RN']",,,,
,PMC,Subgenomic mRNA regulation by a distal RNA element in a (+)-strand RNA virus.,,PMC1369781,,,"Subgenomic (sg) mRNAs are synthesized by (+)-strand RNA viruses to allow for efficient translation of products encoded 3' in their genomes. This strategy also provides a means for regulating the expression of such products via modulation of sg mRNA accumulation. We have studied the mechanism by which sg mRNAs levels are controlled in tomato bushy stunt virus, a small (+)-strand RNA virus which synthesizes two sg mRNAs during infections. Neither the viral capsid nor movement proteins were found to play any significant role in modulating the accumulation levels of either sg mRNA. Deletion analysis did, however, identify a 12-nt-long RNA sequence located approximately 1,000 nt upstream from the site of initiation of sg mRNA2 synthesis that was required specifically for accumulation of sg mRNA2. Further analysis revealed a potential base-pairing interaction between this sequence and a sequence located just 5' to the site of initiation for sg mRNA2 synthesis. Mutant genomes in which this interaction was either disrupted or maintained were analyzed and the results indicated a positive correlation between the predicted stability of the base-pairing interaction and the efficiency of sg mRNA2 accumulation. The functional significance of the long-distance interaction was further supported by phylogenetic sequence analysis which revealed conservation of base-pairing interactions of similar stability and relative position in the genomes of different tombusviruses. It is proposed that the upstream sequence represents a cis-acting RNA element which facilitates sg mRNA accumulation by promoting efficient synthesis of sg mRNA2 via a long-distance RNA-RNA interaction.",,"['Zhang, G', 'Slowinski, V', 'White, K A']",,,,
,PMC,Interference of natural mouse hepatitis virus infection with cytokine production and susceptibility to Trypanosoma cruzi,http://dx.doi.org/10.1046/j.1365-2567.1999.00719.x,PMC2326758,,,"Mouse hepatitis virus (MHV) infection can have a pronounced impact on several investigation areas. Reports on natural MHV outbreaks are rare and most studies have been conducted by deliberately infecting mice with MHV laboratory strains that cause moderate to severe disturbances to the immune system. We have investigated the effects of a natural acute outbreak of MHV in our otherwise specific-pathogen-free (SPF) inbred mouse colonies, and of enzootic chronic MHV infection on cytokine production and resistance to the intracellular pathogen Trypanosoma cruzi. We found that BALB/c and/or C57BL/6 SPF mice that had been injected with T. cruzi blood trypomastigotes from recently MHV-contaminated (MHV(+)) mice developed significantly higher parasite blood counts, accelerated death, and showed higher IL-10 production by spleen cells than their counterparts whose T. cruzi inoculum was derived from MHV-negative (MHV(−)) donors. Interferon-γ (IFN-γ) production by MHV(+) and MHV(−) mice was not significantly different. In contrast, T. cruzi infection of chronically MHV-infected mice did not result in major changes in the course of infection when compared with that observed in mice from MHV(−) colonies, although a trend to higher parasitaemia levels was observed in BALB/c MHV(+) mice. Nevertheless, both BALB/c and C57BL/6 T. cruzi-infected MHV(+) mice had diminished IFN-γ production to parasite-antigen stimulation in comparison with similarly infected MHV(−) mice. Interleukin-10 (IL-10) production levels by spleen cells did not differ between chronic MHV(+) and MHV(−) mice, but IFN-γ neutralization by monoclonal antibody treatment of anti-CD3-stimulated spleen cell cultures showed higher levels of IL-10 synthesis in MHV(+) BALB/c mice.",,"['Torrecilhas, A C T', 'Faquim-Mauro, E', 'Da Silva, A V', 'Abrahamsohn, I A']",,,,
,PMC,Modulation of Nuclear Localization of the Influenza Virus Nucleoprotein through Interaction with Actin Filaments,,PMC104467,,,"The influenza virus genome is transcribed in the nuclei of infected cells but assembled into progeny virions in the cytoplasm. This is reflected in the cellular distribution of the virus nucleoprotein (NP), a protein which encapsidates genomic RNA to form ribonucleoprotein structures. At early times postinfection NP is found in the nucleus, but at later times it is found predominantly in the cytoplasm. NP contains several sequences proposed to act as nuclear localization signals (NLSs), and it is not clear how these are overridden to allow cytoplasmic accumulation of the protein. We find that NP binds tightly to filamentous actin in vitro and have identified a cluster of residues in NP essential for the interaction. Complexes containing RNA, NP, and actin could be formed, suggesting that viral ribonucleoproteins also bind actin. In cells, exogenously expressed NP when expressed at a high level partitioned to the cytoplasm, where it associated with F-actin stress fibers. In contrast, mutants unable to bind F-actin efficiently were imported into the nucleus even under conditions of high-level expression. Similarly, nuclear import of NLS-deficient NP molecules was restored by concomitant disruption of F-actin binding. We propose that the interaction of NP with F-actin causes the cytoplasmic retention of influenza virus ribonucleoproteins.",,"['Digard, Paul', 'Elton, Debra', 'Bishop, Konrad', 'Medcalf, Elizabeth', 'Weeds, Alan', 'Pope, Brian']",,,,
,PMC,Proteolytic Processing of the Open Reading Frame 1b-Encoded Part of Arterivirus Replicase Is Mediated by nsp4 Serine Protease and Is Essential for Virus Replication,,PMC104445,,,"The open reading frame (ORF) 1b-encoded part of the equine arteritis virus (EAV) replicase is expressed by ribosomal frameshifting during genome translation, which results in the production of an ORF1ab fusion protein (345 kDa). Four ORF1b-encoded processing products, nsp9 (p80), nsp10 (p50), nsp11 (p26), and nsp12 (p12), have previously been identified in EAV-infected cells (L. C. van Dinten, A. L. M. Wassenaar, A. E. Gorbalenya, W. J. M. Spaan, and E. J. Snijder, J. Virol. 70:6625–6633, 1996). In the present study, the generation of these four nonstructural proteins was shown to be mediated by the nsp4 serine protease, which is the main viral protease (E. J. Snijder, A. L. M. Wassenaar, L. C. van Dinten, W. J. M. Spaan, and A. E. Gorbalenya, J. Biol. Chem. 271:4864–4871, 1996). Mutagenesis of candidate cleavage sites revealed that Glu-2370/Ser, Gln-2837/Ser, and Glu-3056/Gly are the probable nsp9/10, nsp10/11, and nsp11/12 junctions, respectively. Mutations which abolished ORF1b protein processing were introduced into a recently developed infectious cDNA clone (L. C. van Dinten, J. A. den Boon, A. L. M. Wassenaar, W. J. M. Spaan, and E. J. Snijder, Proc. Natl. Acad. Sci. USA 94:991–997, 1997). An analysis of these mutants showed that the selective blockage of ORF1b processing affected different stages of EAV reproduction. In particular, the mutant with the nsp10/11 cleavage site mutation Gln-2837→Pro displayed an unusual phenotype, since it was still capable of RNA synthesis but was incapable of producing infectious virus.",,"['van Dinten, Leonie C.', 'Rensen, Sietske', 'Gorbalenya, Alexander E.', 'Snijder, Eric J.']",,,,
,PMC,Open Reading Frame 1a-Encoded Subunits of the Arterivirus Replicase Induce Endoplasmic Reticulum-Derived  Double-Membrane Vesicles Which Carry the  Viral Replication Complex,,PMC104444,,,"The replicase of equine arteritis virus (EAV; family Arteriviridae, order Nidovirales) is expressed in the form of two polyproteins (the open reading frame 1a [ORF1a] and ORF1ab proteins). Three viral proteases cleave these precursors into 12 nonstructural proteins, which direct both genome replication and subgenomic mRNA transcription. Immunofluorescence assays showed that most EAV replicase subunits localize to membranes in the perinuclear region of the infected cell. Using replicase-specific antibodies and cryoimmunoelectron microscopy, unusual double-membrane vesicles (DMVs) were identified as the probable site of EAV RNA synthesis. These DMVs were previously observed in cells infected with different arteriviruses but were never implicated in viral RNA synthesis. Extensive electron microscopic analysis showed that they appear to be derived from paired endoplasmic reticulum membranes and that they are most likely formed by protrusion and detachment of vesicular structures with a double membrane. Interestingly, very similar membrane rearrangements were observed upon expression of ORF1a-encoded replicase subunits nsp2 to nsp7 from an alphavirus-based expression vector. Apparently, the formation of a membrane-bound scaffold for the replication complex is a distinct step in the arterivirus life cycle, which is directed by the ORF1a protein and does not depend on other viral proteins and/or EAV-specific RNA synthesis.",,"['Pedersen, Ketil W.', 'van der Meer, Yvonne', 'Roos, Norbert', 'Snijder, Eric J.']",,,,
,PMC,"vig-1, a New Fish Gene Induced by the Rhabdovirus Glycoprotein, Has a Virus-Induced Homologue in Humans  and Shares Conserved Motifs with the MoaA Family",,PMC104424,,,"We used mRNA differential display methodology to analyze the shift of transcription profile induced by the fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV), in rainbow trout leukocytes. We identified and characterized a new gene which is directly induced by VHSV. This VHSV-induced gene (vig-1) encodes a 348-amino-acid protein. vig-1 is highly expressed during the experimental disease in lymphoid organs of the infected fish. Intramuscular injection of a plasmid vector expressing the viral glycoprotein results in vig-1 expression, showing that the external virus protein is sufficient for the induction. vig-1 expression is also obtained by a rainbow trout interferon-like factor, indicating that vig-1 can be induced through different pathways. Moreover, vig-1 is homologous to a recently described human cytomegalovirus-induced gene. Accordingly, vig-1 activation may represent a new virus-induced activation pathway highly conserved in vertebrates. The deduced amino acid sequence of vig-1 is significantly related to sequences required for the biosynthesis of metal cofactors. This suggests that the function of vig-1 may be involved in the nonspecific virus-induced synthesis of enzymatic cofactors of the nitric oxide pathway.",,"['Boudinot, Pierre', 'Massin, Pascale', 'Blanco, Mar', 'Riffault, Sabine', 'Benmansour, Abdenour']",,,,
,PMC,The disulfide-bonded loop of chromogranin B mediates membrane binding and directs sorting from the trans-Golgi network to secretory granules.,http://dx.doi.org/10.1093/emboj/18.4.1059,PMC1171197,,,"The disulfide-bonded loop of chromogranin B (CgB), a regulated secretory protein with widespread distribution in neuroendocrine cells, is known to be essential for the sorting of CgB from the trans-Golgi network (TGN) to immature secretory granules. Here we show that this loop, when fused to the constitutively secreted protein alpha1-antitrypsin (AT), is sufficient to direct the fusion protein to secretory granules. Importantly, the sorting efficiency of the AT reporter protein bearing two loops (E2/3-AT-E2/3) is much higher compared with that of AT with a single disulfide-bonded loop. In contrast to endogenous CgB, E2/3-AT-E2/3 does not undergo Ca2+/pH-dependent aggregation in the TGN. Furthermore, the disulfide-bonded loop of CgB mediates membrane binding in the TGN and does so with 5-fold higher efficiency if two loops are present on the reporter protein. The latter finding supports the concept that under physiological conditions, aggregates of CgB are the sorted units of cargo which have multiple loops on their surface leading to high membrane binding and sorting efficiency of CgB in the TGN.",,"['Glombik, M M', 'Krömer, A', 'Salm, T', 'Huttner, W B', 'Gerdes, H H']",,,,
,PMC,Surgical sterilization of free-ranging wolves.,,PMC1539566,,,"The objective of the study was to determine whether surgical sterilization of both males and females in wolf pairs alters basic wolf social and territorial behaviors. Wolves were located from the air by snow-tracking methods and were tranquilizer-darted from a helicopter. Surgeries were performed either in a tent at the capture site or in a heated building in a nearby village. Six vasectomies and seven uterine horn ligations were performed in January and February of 1996 and 1997. Two females died: one likely related to the capture procedure, the other of a peritonitis unrelated to the surgery. One wolf had a litter. None of the wolves have shown changes in behavioral patterns. Surgical sterilization can be effective, but other, less invasive, fertility control techniques should be investigated.",,"['Spence, C E', 'Kenyon, J E', 'Smith, D R', 'Hayes, R D', 'Baer, A M']",,,,
,PMC,Gamma Interferon Is a Major Suppressive Factor Produced by Activated Human Peripheral Blood Lymphocytes That Is  Able To Inhibit Foamy Virus-Induced Cytopathic Effects,,PMC104007,,,"The activation of human peripheral blood lymphocytes by mitogens or by triggering the T-cell receptor with anti-CD3 antibodies leads to the production of a potent soluble inhibitory activity against foamy virus-induced cytopathic effects in vitro. The inhibitory activity acts in a species-specific manner. As a consequence, the isolation of foamy viruses from blood lymphocytes of infected humans is accelerated in a heterologous coculture system. Antibodies against gamma interferon (IFN-γ) are able to suppress most of the inhibitory activity, suggesting that IFN-γ is the dominant component.",,"['Falcone, Valeria', 'Schweizer, Matthias', 'Toniolo, Antonio', 'Neumann-Haefelin, Dieter', 'Meyerhans, Andreas']",,,,
,PMC,Replication and Packaging of Transmissible Gastroenteritis Coronavirus-Derived Synthetic Minigenomes,,PMC103978,,,"The sequences involved in the replication and packaging of transmissible gastroenteritis virus (TGEV) RNA have been studied. The structure of a TGEV defective interfering RNA of 9.7 kb (DI-C) was described previously (A. Mendez, C. Smerdou, A. Izeta, F. Gebauer, and L. Enjuanes, Virology 217: 495–507, 1996), and a cDNA with the information to encode DI-C RNA was cloned under the control of the T7 promoter. The molecularly cloned DI-C RNA was replicated in trans upon transfection of helper virus-infected cells and inhibited 20-fold the replication of the parental genome. A collection of 14 DI-C RNA deletion mutants (TGEV minigenomes) was synthetically generated and tested for their ability to be replicated and packaged. The smallest minigenome (M33) that was replicated by the helper virus and efficiently packaged was 3.3 kb. A minigenome of 2.1 kb (M21) was also replicated, but it was packaged with much lower efficiency than the M33 minigenome, suggesting that it had lost either the sequences containing the main packaging signal or the required secondary structure in the packaging signal due to alteration of the flanking sequences. The low packaging efficiency of the M21 minigenome was not due to minimum size restrictions. The sequences essential for minigenome replication by the helper virus were reduced to 1,348 nt and 492 nt at the 5′ and 3′ ends, respectively. The TGEV-derived RNA minigenomes were successfully expressed following a two-step amplification system that couples pol II-driven transcription in the nucleus to replication supported by helper virus in the cytoplasm, without any obvious splicing. This system and the use of the reporter gene β-glucuronidase (GUS) allowed minigenome detection at passage zero, making it possible to distinguish replication efficiency from packaging capability. The synthetic minigenomes have been used to design a helper-dependent expression system that produces around 1.0 μg/10(6) cells of GUS.",,"['Izeta, Ander', 'Smerdou, Cristian', 'Alonso, Sara', 'Penzes, Zoltan', 'Mendez, Ana', 'Plana-Durán, Juan', 'Enjuanes, Luis']",,,,
,PMC,Endoproteolytic Processing of the Ebola Virus Envelope Glycoprotein: Cleavage Is Not Required for Function,,PMC103966,,,"Proteolytic processing is required for the activation of numerous viral glycoproteins. Here we show that the envelope glycoprotein from the Zaire strain of Ebola virus (Ebo-GP) is proteolytically processed into two subunits, GP(1) and GP(2), that are likely covalently associated through a disulfide linkage. Murine leukemia virions pseudotyped with Ebo-GP contain almost exclusively processed glycoprotein, indicating that this is the mature form of Ebo-GP. Mutational analysis identified a dibasic motif, reminiscent of furin-like protease processing sites, as the Ebo-GP cleavage site. However, analysis of Ebo-GP processing in LoVo cells that lack the proprotein convertase furin demonstrated that furin is not required for processing of Ebo-GP. In sharp contrast to other viral systems, we found that an uncleaved mutant of Ebo-GP was able to mediate infection of various cell lines as efficiently as the wild-type, proteolytically cleaved glycoprotein, indicating that cleavage is not required for the activation of Ebo-GP despite the conservation of a dibasic cleavage site in all filoviral envelope glycoproteins.",,"['Wool-Lewis, Rouven J.', 'Bates, Paul']",,,,
,PMC,Development and Applications of a Bovine Coronavirus Antigen Detection Enzyme-Linked  Immunosorbent Assay,,PMC95672,,,"We developed a monoclonal antibody-based, antigen capture sandwich enzyme-linked immunosorbent assay (ELISA) for bovine coronavirus. We compared the ELISA with electron microscopy and the hemagglutination test and found a close correlation between them. The sensitivity of the ELISA was 10(4) bovine coronavirus particles per ml of 10% fecal suspension. Compared with electron microscopy, bovine coronavirus ELISA had 96% specificity.",,"['Schoenthaler, S. L.', 'Kapil, S.']",,,,
,PMC,Polymeric Display of Immunogenic Epitopes from Herpes Simplex Virus and Transmissible Gastroenteritis Virus  Surface Proteins on an Enteroadherent Fimbria,,PMC95656,,,"The strong immunogenicity of bacterial fimbriae results from their polymeric and proteinaceous nature, and the protective role of these immunogens in experimental or commercial vaccines is associated with their capacity to induce antiadhesive antibodies. Fimbria-mediated intestinal colonization by enteropathogens typically leads to similar antibody responses. The possibility of taking advantage of these properties was investigated by determining whether enteroadhesive fimbriae, like the 987P fimbriae of enterotoxigenic Escherichia coli, can serve as carriers for foreign antigens without losing their adhesive characteristics. Random linker insertion mutagenesis of the fasA gene encoding the major 987P subunit identified five different mutants expressing wild-type levels of fimbriation. The linker insertion sites of these mutants were used to introduce three continuous segments of viral surface glycoproteins known to be accessible to antibodies. These segments encode residues 11 to 19 or 272 to 279 of herpes simplex virus type 1 (HSV-1) glycoprotein D [gD(11–19) and gD(272–279), respectively] or residues 379 to 388 of the transmissible gastroenteritis virus (TGEV) spike protein [S(379–388)]. Studies of bacteria expressing fimbriae incorporating mutated FasA subunits alone or together with wild-type FasA subunits (hybrid fimbriae) indicated that foreign epitopes were best exported and displayed on assembled fimbriae when they were inserted near the amino terminus of FasA. Fimbriated bacteria expressing FasA subunits carrying the HSV gD(11–19) or the TGEV S(379–388) epitope inserted between the second and third residues of mature FasA elicited high levels of foreign epitope antibodies in all rabbits immunized parenterally. Antibodies against the HSV epitope were also shown to recognize the epitope in the context of the whole gD protein. Because the 987P adhesive subunit FasG was shown to be present on mutated fimbriae and to mediate bacterial attachment to porcine intestinal receptors, polymeric display of foreign epitopes on 987P offers new opportunities to test the potential beneficial effect of enteroadhesion for mucosal immunization and protection against various enteric pathogens.",,"['Rani, D. B. Rajini', 'Bayer, Manfred E.', 'Schifferli, Dieter M.']",,,,
,PMC,T-cell populations in the pig intestinal lamina propria: memory cells with unusual phenotypic characteristics,http://dx.doi.org/10.1046/j.1365-2567.1999.00658.x,PMC2326712,,,"We have previously presented evidence of a highly organized and compartmentalized structure of the small intestinal lamina propria of the pig. In this study, we conducted a detailed analysis of the T-cell populations found at this site, and compared these T cells with cell populations found in other tissue sites and the periphery. We showed that the CD4(+) and CD8(+) T-cell populations found in the pig gut are of memory phenotype, defined by CD45 isoform expression, but show few signs of recent activation. They show a high degree of phenotypic and therefore presumably functional homogeneity. Both CD4- and CD8-positive cells show strong parallels in the patterns of surface molecule expression, suggesting similar pressures on differentiation. The unique combination of surface molecules found on lamina propria T cells is found only infrequently on cells in other lymphoid sites.",,"['Haverson, K', 'Bailey, M', 'Stokes, C R']",,,,
,PMC,Molecular Characterization of a Bovine Enteric Calicivirus: Relationship to the Norwalk-Like Viruses,,PMC103897,,,"Jena virus (JV) is a noncultivatable bovine enteric calicivirus associated with diarrhea in calves and was first described in Jena, Germany. The virus was serially passaged 11 times in colostrum-deprived newborn calves and caused diarrheal disease symptoms at each passage. The complete JV genome sequence was determined by using cDNA made from partially purified virus obtained from a single stool sample. JV has a positive-sense single-stranded RNA genome which is 7,338 nucleotides in length, excluding the poly(A) tail. JV genome organization is similar to that of the human Norwalk-like viruses (NLVs), with three separate open reading frames (ORFs) and a 24-nucleotide sequence motif located at the 5′ terminus of the genome and at the start of ORF 2. The polyprotein (ORF 1) consists of 1,680 amino acids and has the characteristic 2C helicase, 3C protease, and 3D RNA polymerase motifs also found in the NLVs. However, comparison of the N-terminal 100 amino acids of the JV polyprotein with those of the group 1 and group 2 NLVs showed a considerable divergence in sequence. The capsid protein (ORF 2) at 519 amino acids is smaller than that of all other caliciviruses. JV ORF 2 was translated in vitro to produce a 55-kDa protein that reacted with postinfection serum but not preinfection serum. Phylogenetic studies based on partial RNA polymerase sequences indicate that within the Caliciviridae JV is most closely related to the group 1 NLVs.",,"['Liu, B. L.', 'Lambden, P. R.', 'Günther, H.', 'Otto, P.', 'Elschner, M.', 'Clarke, I. N.']",,,,
,PMC,Polypyrimidine Tract-Binding Protein Binds to the Leader RNA of Mouse Hepatitis Virus and Serves as a Regulator of Viral Transcription,,PMC103887,,,"A cellular protein, previously described as p55, binds specifically to the plus strand of the mouse hepatitis virus (MHV) leader RNA. We have purified this protein and determined by partial peptide sequencing that it is polypyrimidine tract-binding protein (PTB) (also known as heterogeneous nuclear ribonucleoprotein [hnRNP] I), a nuclear protein which shuttles between the nucleus and cytoplasm. PTB plays a role in the regulation of alternative splicing of pre-mRNAs in normal cells and translation of several viruses. By UV cross-linking and immunoprecipitation studies using cellular extracts and a recombinant PTB, we have established that PTB binds to the MHV plus-strand leader RNA specifically. Deletion analyses of the leader RNA mapped the PTB-binding site to the UCUAA pentanucleotide repeats. Using a defective-interfering RNA reporter system, we have further shown that the PTB-binding site in the leader RNA is critical for MHV RNA synthesis. This and our previous study (H.-P. Li, X. Zhang, R. Duncan, L. Comai, and M. M. C. Lai, Proc. Natl. Acad. Sci. USA 94:9544–9549, 1997) combined thus show that two cellular hnRNPs, PTB and hnRNP A1, bind to the transcription-regulatory sequences of MHV RNA and may participate in its transcription.",,"['Li, Hsin-Pai', 'Huang, Peiyong', 'Park, Sungmin', 'Lai, Michael M. C.']",,,,
,PMC,Persistent Infection Promotes Cross-Species Transmissibility  of Mouse Hepatitis Virus,,PMC103870,,,"Persistent infection with mouse hepatitis virus (MHV) strain A59 in murine DBT (delayed brain tumor) cells resulted in the emergence of host range variants, designated V51A and V51B, at 210 days postinfection. These host range mutants replicated efficiently in normally nonpermissive Chinese hamster ovary (CHO), in human hepatocarcinoma (HepG2), and to a lesser extent in human breast carcinoma (MCF7) cell lines. Little if any replication was noted in baby hamster kidney (BHK), green African monkey kidney (COS-7), feline kidney (CRFK), and swine testicular (ST) cell lines. By fluorescent antibody (FA) staining, persistent viruses V10B and V30B, isolated at days 38 and 119 days postinfection, also demonstrated very low levels of replication in human HepG2 cells. These data suggest that persistence may rapidly select for host range expansion of animal viruses. Pretreatment of HepG2 cells with a polyclonal antibody directed against human carcinoembryonic antigens (CEA) or with some monoclonal antibodies (Col-1, Col-4, Col-12, and Col-14) that bind human CEA significantly inhibited V51B infection. Under identical conditions, little or no blockade was evident with other monoclonal antibodies (kat4c or Col-6) which also bind the human CEA glycoproteins. In addition, an antibody (EDDA) directed against irrelevant antigens did not block V51B replication. Pretreatment with the Col-4 and Col-14 antibodies did not block Sindbis virus replication in HepG2 cells or MHV infection in DBT cells, suggesting that one or more CEA glycoproteins likely functioned as receptors for V51B entry into human cell lines. To test this hypothesis, the human biliary glycoprotein (Bgp) and CEA genes were cloned and expressed in normally nonpermissive BHK cell lines by using noncytopathic Sindbis virus replicons (pSinRep19). By growth curves and FA staining, human CEA and to a much lesser extent human Bgp functioned as receptors for V51B entry. Furthermore, V51B replication was blocked with polyclonal antiserum directed against human CEA and Bgp. Under identical conditions, the parental MHV strain A59 failed to replicate in BHK cells expressing human Bgp or CEA. These data suggest that MHV persistence may promote virus cross-species transmissibility by selecting for virus variants that recognize phylogenetic homologues of the normal receptor.",,"['Baric, Ralph S.', 'Sullivan, Eileen', 'Hensley, Lisa', 'Yount, Boyd', 'Chen, Wan']",,,,
,PMC,Two Nucleotides Immediately Upstream of the Essential A(6)G(3) Slippery Sequence Modulate the Pattern of G Insertions  during Sendai Virus mRNA Editing,,PMC103839,,,"Editing of paramyxovirus P gene mRNAs occurs cotranscriptionally and functions to fuse an alternate downstream open reading frame to the N-terminal half of the P protein. G residues are inserted into a short G run contained within a larger purine run (A(n)G(n)) in this process, by a mechanism whereby the transcribing polymerase stutters (i.e., reads the same template cytosine more than once). Although Sendai virus (SeV) and bovine parainfluenza virus type 3 (bPIV3) are closely related, the G insertions in their P mRNAs are distributed differently. SeV predominantly inserts a single G residue within the G run of the sequence 5′ AACAAAAAAGGG, whereas bPIV3 inserts one to six G’s at roughly equal frequency within the sequence 5′ AUUAAAAAAGGGG (differences are underlined). We have examined how the cis-acting editing sequence determines the number of G’s inserted, both in a transfected cell system using minigenome analogues and by generating recombinant viruses. We found that the presence of four rather than three G’s in the purine run did not affect the distribution of G insertions. However, when the underlined AC of the SeV sequence was replaced by the UU found in bPIV3, the editing phenotype from both the minigenome and the recombinant virus resembled that found in natural bPIV3 infections (i.e., a significant fraction of the mRNAs contained two to six G insertions). The two nucleotides located just upstream of the polypurine tract are thus key determinants of the editing phenotype of these viruses. Moreover, the minimum number of A residues that will promote SeV editing phenotype is six but can be reduced to five when the upstream AC is replaced by UU. A model for how the upstream dinucleotide controls the insertion phenotype is presented.",,"['Hausmann, Stéphane', 'Garcin, Dominique', 'Morel, Anne-Sophie', 'Kolakofsky, Daniel']",,,,
,PMC,Porcine Reproductive and Respiratory Syndrome Virus Comparison: Divergent Evolution on Two Continents,,PMC103831,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) is a recently described arterivirus responsible for disease in swine worldwide. Comparative sequence analysis of 3′-terminal structural genes of the single-stranded RNA viral genome revealed the presence of two genotypic classes of PRRSV, represented by the prototype North American and European strains, VR-2332 and Lelystad virus (LV), respectively. To better understand the evolution and pathogenicity of PRRSV, we obtained the 12,066-base 5′-terminal nucleotide sequence of VR-2332, encoding the viral replication activities, and compared it to those of LV and other arteriviruses. VR-2332 and LV differ markedly in the 5′ leader and sections of the open reading frame (ORF) 1a region. The ORF 1b sequence was nearly colinear but varied in similarity of proteins encoded in identified regions. Furthermore, molecular and biochemical analysis of subgenomic mRNA (sgmRNA) processing revealed extensive variation in the number of sgmRNAs which may be generated during infection and in the lengths of noncoding sequence between leader-body junctions and the translation-initiating codon AUG. In addition, VR-2332 and LV select different leader-body junction sites from a pool of similar candidate sites to produce sgmRNA 7, encoding the viral nucleocapsid protein. The presence of substantial variations across the entire genome and in sgmRNA processing indicates that PRRSV has evolved independently on separate continents. The near-simultaneous global emergence of a new swine disease caused by divergently evolved viruses suggests that changes in swine husbandry and management may have contributed to the emergence of PRRS.",,"['Nelsen, Chris J.', 'Murtaugh, Michael P.', 'Faaberg, Kay S.']",,,,
,PMC,Processing of the Human Coronavirus 229E Replicase Polyproteins by the Virus-Encoded 3C-Like Proteinase: Identification of Proteolytic Products and Cleavage Sites Common to pp1a and pp1ab,,PMC103821,,,"Replicase gene expression by the human coronavirus 229E involves the synthesis of two large polyproteins, pp1a and pp1ab. Experimental evidence suggests that these precursor molecules are subject to extensive proteolytic processing. In this study, we show that a chymotrypsin-like enzyme, the virus-encoded 3C-like proteinase (3CL(pro)), cleaves within a common region of pp1a and pp1ab (amino acids 3490 to 4068) at four sites. trans-cleavage assays revealed that polypeptides of 5, 23, 12, and 16 kDa are processed from pp1a/pp1ab by proteolysis of the peptide bonds Q3546/S3547, Q3629/S3630, Q3824/N3825, and Q3933/A3934. Relative rate constants for the 3CL(pro)-mediated cleavages Q2965/A2966, Q3267/S3268, Q3824/N3825, and Q3933/A3934 were derived by competition experiments using synthetic peptides and recombinant 3CL(pro). The results indicate that coronavirus cleavage sites differ significantly with regard to their susceptibilities to proteolysis by 3CL(pro). Finally, immunoprecipitation with specific rabbit antisera was used to detect the pp1a/pp1ab processing end products in virus-infected cells, and immunofluorescence data that suggest an association of these polypeptides with intracellular membranes were obtained.",,"['Ziebuhr, John', 'Siddell, Stuart G.']",,,,
,PMC,Ribosomal Protein L3 Mutants Alter Translational Fidelity and Promote Rapid Loss of the Yeast Killer Virus,,PMC83896,,,"Programmed −1 ribosomal frameshifting is utilized by a number of RNA viruses as a means of ensuring the correct ratio of viral structural to enzymatic proteins available for viral particle assembly. Altering frameshifting efficiencies upsets this ratio, interfering with virus propagation. We have previously demonstrated that compounds that alter the kinetics of the peptidyl-transfer reaction affect programmed −1 ribosomal frameshift efficiencies and interfere with viral propagation in yeast. Here, the use of a genetic approach lends further support to the hypothesis that alterations affecting the ribosome’s peptidyltransferase activity lead to changes in frameshifting efficiency and virus loss. Mutations in the RPL3 gene, which encodes a ribosomal protein located at the peptidyltransferase center, promote approximately three- to fourfold increases in programmed −1 ribosomal frameshift efficiencies and loss of the M(1) killer virus of yeast. The mak8-1 allele of RPL3 contains two adjacent missense mutations which are predicted to structurally alter the Mak8-1p. Furthermore, a second allele that encodes the N-terminal 100 amino acids of L3 (called L3Δ) exerts a trans-dominant effect on programmed −1 ribosomal frameshifting and killer virus maintenance. Taken together, these results support the hypothesis that alterations in the peptidyltransferase center affect programmed −1 ribosomal frameshifting.",,"['Peltz, Stuart W.', 'Hammell, Amy B.', 'Cui, Ying', 'Yasenchak, Jason', 'Puljanowski, Lara', 'Dinman, Jonathan D.']",,,,
,PMC,Chronic airway disease: the infection connection.,,PMC2194299,,,,,"['Greenberg, S. B.', 'Atmar, R. L.']",,,,
,PMC,Formation and Amplification of a Novel Tombusvirus Defective RNA Which Lacks the 5′ Nontranslated Region  of the Viral Genome,,PMC110502,,,"Defective interfering (DI) RNAs of tomato bushy stunt virus (TBSV) are small, subgenomic, helper-dependent replicons that are believed to be generated primarily by aberrant events during replication of the plus-sense RNA genome. Prototypical TBSV DI RNAs contain four noncontiguous segments (regions I through IV) derived from the 5′ nontranslated region (NTR) (I), an internal section (II), and the 3′-terminal portion (III and IV) of the viral genome. We have studied the formation of these molecules by using engineered precursor DI RNA transcripts and report here the consistent accumulation of a novel defective RNA species, designated RNA B. Northern blot, primer extension, and sequence analyses indicated that, unlike prototypical DI RNAs, RNA B lacks region I. In vitro transcripts corresponding to the region II-III-IV structure of RNA B were amplified when coinoculated with helper, indicating that the 5′ NTR of the genome does not harbor cis-acting replication elements essential for viral RNA replication. Region I is, however, important for DI RNA fitness, since molecules lacking it accumulated to significantly lower levels (∼10-fold reduction). Analysis of the minus-strand sequence of region I led to the identification of an RNA undecamer sequence, arranged in tandem, at its very 3′ terminus. Additional variants of the undecamer motif were also identified at internal positions in region I and in the negative strands of regions II, III, and IV. Features of the undecamer motif, the consensus of which is (−)3′-CCCAAAGAGAG, are consistent with a role as a cis-acting replication element. It is proposed that the ability of RNA B to be amplified is due, in part, to compensatory effects of a strategically positioned undecamer motif in region II. Possible replicase-mediated mechanisms for the generation of this novel viral RNA are also presented.",,"['Wu, Baodong', 'White, K. Andrew']",,,,
,PMC,Targeted Recombination within the Spike Gene of Murine Coronavirus Mouse Hepatitis Virus-A59: Q159 Is a Determinant of Hepatotropism,,PMC110472,,,"Previous studies of a group of mutants of the murine coronavirus mouse hepatitis virus (MHV)-A59, isolated from persistently infected glial cells, have shown a strong correlation between a Q159L amino acid substitution in the S1 subunit of the spike gene and a loss in the ability to induce hepatitis and demyelination. To determine if Q159L alone is sufficient to cause these altered pathogenic properties, targeted RNA recombination was used to introduce a Q159L amino acid substitution into the spike gene of MHV-A59. Recombination was carried out between the genome of a temperature-sensitive mutant of MHV-A59 (Alb4) and RNA transcribed from a plasmid (pFV1) containing the spike gene as well as downstream regions, through the 3′ end, of the MHV-A59 genome. We have selected and characterized two recombinant viruses containing Q159L. These recombinant viruses (159R36 and 159R40) replicate in the brains of C57BL/6 mice and induce encephalitis to a similar extent as wild-type MHV-A59. However, they exhibit a markedly reduced ability to replicate in the liver or produce hepatitis compared to wild-type MHV-A59. These viruses also exhibit reduced virulence and reduced demyelination. A recombinant virus containing the wild-type MHV-A59 spike gene, wtR10, behaved essentially like wild-type MHV-A59. This is the first report of the isolation of recombinant viruses containing a site-directed mutation, encoding an amino acid substitution, within the spike gene of any coronavirus. This technology will allow us to begin to map the molecular determinants of pathogenesis within the spike glycoprotein.",,"['Leparc-Goffart, Isabelle', 'Hingley, Susan T.', 'Chua, Ming Ming', 'Phillips, Joanna', 'Lavi, Ehud', 'Weiss, Susan R.']",,,,
,PMC,Targeting of a Short Peptide Derived from the Cytoplasmic Tail of the G1 Membrane Glycoprotein of Uukuniemi Virus (Bunyaviridae) to the Golgi Complex,,PMC110468,,,"Members of the Bunyaviridae family acquire an envelope by budding through the lipid bilayer of the Golgi complex. The budding compartment is thought to be determined by the accumulation of the two heterodimeric membrane glycoproteins G1 and G2 in the Golgi. We recently mapped the retention signal for Golgi localization in one Bunyaviridae member (Uukuniemi virus) to the cytoplasmic tail of G1. We now show that a myc-tagged 81-residue G1 tail peptide expressed in BHK21 cells is efficiently targeted to the Golgi complex and retained there during a 3-h chase. Green-fluorescence protein tagged at either end with this peptide or with a C-terminally truncated 60-residue G1 tail peptide was also efficiently targeted to the Golgi. The 81-residue peptide colocalized with mannosidase II (a medial Golgi marker) and partially with p58 (an intermediate compartment marker) and TGN38 (a trans-Golgi marker). In addition, the 81-residue tail peptide induced the formation of brefeldin A-resistant vacuoles that did not costain with markers for other membrane compartments. Removal of the first 10 N-terminal residues had no effect on the Golgi localization but abolished the vacuolar staining. The shortest peptide still able to become targeted to the Golgi encompassed residues 10 to 40. Subcellular fractionation showed that the 81-residue tail peptide was associated with microsomal membranes. Removal of the two palmitylation sites from the tail peptide did not affect Golgi localization and had only a minor effect on the association with microsomal membranes. Taken together, the results provide strong evidence that Golgi retention of the heterodimeric G1-G2 spike protein complex of Uukuniemi virus is mediated by a short region in the cytoplasmic tail of the G1 glycoprotein.",,"['Andersson, Agneta M.', 'Pettersson, Ralf F.']",,,,
,PMC,Cytokine Response in Multiple Lymphoid Tissues during the Primary Phase of Feline Immunodeficiency Virus Infection,,PMC110431,,,"Type 1 and 2 cytokine mRNA responses were measured at various time periods and in various lymphoid compartments during the acute stage (first 4 months) of feline immunodeficiency virus (FIV) infection in laboratory cats. Cytokine responses were correlated with virus replication. Virus was detected in plasma and tissue from day 14 postinfection (p.i.) onward, peaked at 56 to 70 days, and declined greatly by 70 days. Virus replication was highest in the thymus, followed by spleen, mesenteric lymph nodes, and cervical lymph nodes. Baseline cytokine levels were highest in the mesenteric lymph nodes and lowest in the cervical lymph nodes. Cytokine upregulation after FIV infection was most dramatic in the cervical lymph nodes, with the greatest increase in interleukin-10 (IL-10) and gamma interferon (IFN-γ). Cytokine transcription in the mesenteric lymph node increased above baseline by day 14 p.i. for IFN-γ, IL-12p40, IL-4, and IL-10, while elevations in the spleen were mainly for IFN-γ, IL-12p40 and IL-10. An increase in IFN-γ, IL-10, and IL-12p40 occurred in the thymus at day 56 p.i., concomitant with the onset of thymitis. In general, type 2 cytokines (IL-4 and IL-10) were increased greater than 1 log over baseline, while the elevations in type 1 cytokines were less than 1 log. In the tissues tested, CD4(+) cells were the primary source of IL-2, IL-4, and IL-10. Both CD4(+) and CD8(+) cells produced IFN-γ, while no cytokine mRNA was detected in B cells. These results demonstrate the presence of a heterogeneous cytokine response in lymphoid tissues during the primary stage of FIV infection. The nature and intensity of the response differed from one compartment to the other and, in the case of the thymus, also with inflammatory changes. Although limited in scope, the present study confirms the usefulness of the FIV infection model in studying early cytokine events that lead to the secondary subclinical carrier state typical of most lentivirus infections.",,"['Dean, Gregg A.', 'Pedersen, Niels C.']",,,,
,PMC,Posttranscriptional Control of Gene Expression in Yeast,,PMC98953,,,"Studies of the budding yeast Saccharomyces cerevisiae have greatly advanced our understanding of the posttranscriptional steps of eukaryotic gene expression. Given the wide range of experimental tools applicable to S. cerevisiae and the recent determination of its complete genomic sequence, many of the key challenges of the posttranscriptional control field can be tackled particularly effectively by using this organism. This article reviews the current knowledge of the cellular components and mechanisms related to translation and mRNA decay, with the emphasis on the molecular basis for rate control and gene regulation. Recent progress in characterizing translation factors and their protein-protein and RNA-protein interactions has been rapid. Against the background of a growing body of structural information, the review discusses the thermodynamic and kinetic principles that govern the translation process. As in prokaryotic systems, translational initiation is a key point of control. Modulation of the activities of translational initiation factors imposes global regulation in the cell, while structural features of particular 5′ untranslated regions, such as upstream open reading frames and effector binding sites, allow for gene-specific regulation. Recent data have revealed many new details of the molecular mechanisms involved while providing insight into the functional overlaps and molecular networking that are apparently a key feature of evolving cellular systems. An overall picture of the mechanisms governing mRNA decay has only very recently begun to develop. The latest work has revealed new information about the mRNA decay pathways, the components of the mRNA degradation machinery, and the way in which these might relate to the translation apparatus. Overall, major challenges still to be addressed include the task of relating principles of posttranscriptional control to cellular compartmentalization and polysome structure and the role of molecular channelling in these highly complex expression systems.",,"McCarthy, John E. G.",,,,
,PMC,Virus Maturation by Budding,,PMC98943,,,"Enveloped viruses mature by budding at cellular membranes. It has been generally thought that this process is driven by interactions between the viral transmembrane proteins and the internal virion components (core, capsid, or nucleocapsid). This model was particularly applicable to alphaviruses, which require both spike proteins and a nucleocapsid for budding. However, genetic studies have clearly shown that the retrovirus core protein, i.e., the Gag protein, is able to form enveloped particles by itself. Also, budding of negative-strand RNA viruses (rhabdoviruses, orthomyxoviruses, and paramyxoviruses) seems to be accomplished mainly by internal components, most probably the matrix protein, since the spike proteins are not absolutely required for budding of these viruses either. In contrast, budding of coronavirus particles can occur in the absence of the nucleocapsid and appears to require two membrane proteins only. Biochemical and structural data suggest that the proteins, which play a key role in budding, drive this process by forming a three-dimensional (cage-like) protein lattice at the surface of or within the membrane. Similarly, recent electron microscopic studies revealed that the alphavirus spike proteins are also engaged in extensive lateral interactions, forming a dense protein shell at the outer surface of the viral envelope. On the basis of these data, we propose that the budding of enveloped viruses in general is governed by lateral interactions between peripheral or integral membrane proteins. This new concept also provides answers to the question of how viral and cellular membrane proteins are sorted during budding. In addition, it has implications for the mechanism by which the virion is uncoated during virus entry.",,"['Garoff, Henrik', 'Hewson, Roger', 'Opstelten, Dirk-Jan E.']",,,,
,PMC,The rhinovirus type 14 genome contains an internally located RNA structure that is required for viral replication.,,PMC1369726,,,"Cis-acting RNA signals are required for replication of positive-strand viruses such as the picornaviruses. Although these generally have been mapped to the 5' and/or 3' termini of the viral genome, RNAs derived from human rhinovirus type 14 are unable to replicate unless they contain an internal cis-acting replication element (cre) located within the genome segment encoding the capsid proteins. Here, we show that the essential cre sequence is 83-96 nt in length and located between nt 2318-2413 of the genome. Using dicistronic RNAs in which translation of the P1 and P2-P3 segments of the polyprotein were functionally dissociated, we further demonstrate that translation of the cre sequence is not required for RNA replication. Thus, although it is located within a protein-coding segment of the genome, the cre functions as an RNA entity. Computer folds suggested that cre sequences could form a stable structure in either positive- or minus-strand RNA. However, an analysis of mutant RNAs containing multiple covariant and non-covariant nucleotide substitutions within these putative structures demonstrated that only the predicted positive-strand structure is essential for efficient RNA replication. The absence of detectable minus-strand synthesis from RNAs that lack the cre suggests that the cre is required for initiation of minus-strand RNA synthesis. Since a lethal 3' noncoding region mutation could be partially rescued by a compensating mutation within the cre, the cre appears to participate in a long-range RNA-RNA interaction required for this process. These data provide novel insight into the mechanisms of replication of a positive-strand RNA virus, as they define the involvement of an internally located RNA structure in the recognition of viral RNA by the viral replicase complex. Since internally located RNA replication signals have been shown to exist in several other positive-strand RNA virus families, these observations are potentially relevant to a wide array of related viruses.",,"['McKnight, K L', 'Lemon, S M']",,,,
,PMC,Antigenic Structure of the Nucleocapsid Protein of Porcine Reproductive and Respiratory Syndrome Virus,,PMC96200,,,"A collection of 12 monoclonal antibodies (MAbs) raised against porcine reproductive and respiratory syndrome (PRRS) virus was used to study the antigenic structure of the virus nucleocapsid protein (N). The full-length N gene, encoded by open reading frame 7, was cloned from the Canadian PRRS virus, PA-8. Deletions were introduced into the N gene to produce a series of nine overlapping protein fragments ranging in length from 25 to 112 amino acids. The individual truncated genes were cloned as glutathione S-transferase fusions into a eukaryotic expression vector downstream of the T7 RNA polymerase promoter. HeLa cells infected with recombinant vaccinia virus expressing T7 RNA polymerase were transfected with plasmid DNA encoding the N protein fragments, and the antigenicity of the synthesized proteins was analyzed by immunoprecipitation. Based on the immunoreactivities of the N protein deletion mutants with the panel of N-specific MAbs, five domains of antigenic importance were identified. MAbs SDOW17, SR30, and 5H2.3B12.1C9 each identified independent domains defined by amino acids 30 to 52, 69 to 123, and 37 to 52, respectively. Seven of the MAbs tested specifically recognized the local protein conformation formed in part by the amino acid residues 52 to 69. Furthermore, deletion of 11 amino acids from the carboxy terminus of the nucleocapsid protein disrupted the epitope configuration recognized by all of the conformation-dependent MAbs, suggesting that the carboxy-terminal region plays an important role in maintaining local protein conformation.",,"['Wootton, Sarah K.', 'Nelson, Eric A.', 'Yoo, Dongwan']",,,,
,PMC,Regulated multicistronic expression technology for mammalian metabolic engineering,http://dx.doi.org/10.1023/A:1008037916674,PMC3449837,,,"Contemporary basic research is rapidly revealing increasingly complex molecular regulatory networks which are often interconnected via key signal integrators. These connections among regulatory and catalytic networks often frustrate bioengineers as promising metabolic engineering strategies are bypassed by compensatory metabolic responses or cause unexpected, undesired outcomes such as apoptosis, product protein degradation or inappropriate post- translational modification. Therefore, for metabolic engineering to achieve greater success in mammalian cell culture processes and to become important for future applications such as gene therapy and tissue engineering, this technology must be enhanced to allow simultaneous, in cases conditional, reshaping of metabolic pathways to access difficult-to-attain cell states. Recent advances in this new territory of multigene metabolic engineering are intimately linked to the development of multicistronic expression technology which allows the simultaneous, and in some cases, regulated expression of several genes in mammalian cells. Here we review recent achievements in multicistronic expression technology in view of multigene metabolic engineering.",,"['Fussenegger, Martin', 'Moser, Samuel', 'Bailey, James E.']",,,,
,PMC,Murine Coronavirus-Induced Subacute Fatal Peritonitis in C57BL/6 Mice Deficient in Gamma Interferon,,PMC110348,,,"Gamma interferon-deficient (IFN-γ−/−) mice with a C57BL/6 background were infected intraperitoneally with mouse hepatitis virus strain JHM (JHMV). In contrast to IFN-γ-+/− and IFN-γ+/+ mice, JHMV persisted in IFN-γ−/− mice and induced death during the subacute phase of the infection. Unexpectedly, infected IFN-γ−/− mice showed severe peritonitis accompanying the accumulation of a viscous fluid in the abdominal and thoracic cavities in the subacute phase. Destructive changes of hepatocytes were not observed. Administration of recombinant IFN-γ protracted the survival time of IFN-γ−/− mice after JHMV infection. These results demonstrate that IFN-γ plays a critical role in viral clearance in JHMV infection. They also show that a resultant persistent JHMV infection induces another form of disease in IFN-γ−/− mice, which bears a resemblance to feline infectious peritonitis in cats.",,"['Kyuwa, Shigeru', 'Tagawa, Yoh-ichi', 'Shibata, Shinwa', 'Doi, Kunio', 'Machii, Kenji', 'Iwakura, Yoichiroh']",,,,
,PMC,Mutations in the N Terminus of the Brome Mosaic Virus Polymerase Affect Genetic RNA-RNA Recombination,,PMC110338,,,"Previously, we have observed that mutations in proteins 1a and 2a, the two virally encoded components of the brome mosaic virus (BMV) replicase, can affect the frequency of recombination and the locations of RNA recombination sites (P. D. Nagy, A. Dzianott, P. Ahlquist, and J. J. Bujarski, J. Virol. 69:2547–2556, 1995; M. Figlerowicz, P. D. Nagy, and J. J. Bujarski, Proc. Natl. Acad. Sci. USA 94:2073–2078, 1997). Also, it was found before that the N-terminal domain of 2a, the putative RNA polymerase protein, participates in the interactions between 1a and 2a (C. C. Kao, R. Quadt, R. P. Hershberger, and P. Ahlquist, J. Virol. 66:6322–6329, 1992; E. O’Reilly, J. Paul, and C. C. Kao, J. Virol. 71:7526–7532, 1997). In this work, we examine how mutations within the N terminus of 2a influence RNA recombination in BMV. Because of the likely electrostatic character of 1a-2a interactions, five 2a mutants, MF1 to MF5, were generated by replacing clusters of acidic amino acids with their neutral counterparts. MF2 and MF5 retained nearly wild-type levels of 1a-2a interaction and were infectious in Chenopodium quinoa. However, compared to that in wild-type virus, the frequency of nonhomologous recombination in both MF2 and MF5 was markedly decreased. Only in MF2 was the frequency of homologous recombination reduced and the occurrence of imprecise homologous recombination increased. In MF5 there was also a 3′ shift in the positions of homologous crossovers. The observed effects of MF2 and MF5 reveal that the 2a N-terminal domain participates in different ways in homologous and in nonhomologous BMV RNA recombination. This work maps specific locations within the N terminus involved in 1a-2a interaction and in recombination and further suggests that the mechanisms of the two types of crossovers in BMV are different.",,"['Figlerowicz, M.', 'Nagy, P. D.', 'Tang, N.', 'Kao, C. C.', 'Bujarski, J. J.']",,,,
,PMC,Cytotoxic T-Lymphocyte Precursor Frequencies in BALB/c Mice after Acute Respiratory Syncytial Virus (RSV) Infection or Immunization with a Formalin-Inactivated RSV Vaccine,,PMC110314,,,"A better understanding of the immune response to live and formalin-inactivated respiratory syncytial virus (RSV) is important for developing nonlive vaccines. In this study, major histocompatibility complex (MHC) class I- and II-restricted, RSV-specific cytotoxic T-lymphocyte precursor (CTLp) frequencies were determined in bronchoalveolar lavage (BAL) samples and spleen lymphocytes of BALB/c mice intranasally infected with live RSV or intramuscularly inoculated with formalin-inactivated RSV (FI-RSV). After RSV infection, both class I- and class II-restricted CTLps were detected by day 4 or 5 postinfection (p.i.). Peak CTLp frequencies were detected by day 7 p.i. The class II-restricted CTLp frequencies in the BAL following RSV infection were less than class I-restricted CTLp frequencies through day 14 p.i., during which class I-restricted CTLp frequencies remained elevated, but then declined by 48 days p.i. The frequencies of class II-restricted CTLps in the BAL were 2- to 10-fold less than those of class I-restricted CTLps. For spleen cells, frequencies of both MHC class I- and II-restricted CTLps to live RSV were similar. In contrast, class II-restricted CTLps predominated in FI-RSV-vaccinated mice. RSV challenge of vaccinated mice resulted in an increase in the frequency of class I-restricted CTLps at day 3 p.i. but did not enhance class II-restricted CTLp frequencies. These studies demonstrate differences in the CTLp response to live RSV infection compared with FI-RSV immunization and help define possible mechanisms of enhanced disease after FI-RSV immunization. In addition, these studies provide a quantitative means to address potential vaccine candidates by examining both MHC class I- and II-restricted CTLp frequencies.",,"['Tripp, Ralph A.', 'Anderson, Larry J.']",,,,
,PMC,The 3′-Untranslated Region of Hepatitis C Virus RNA  Enhances Translation from an Internal Ribosomal  Entry Site,,PMC110295,,,"Translation of most eukaryotic mRNAs and many viral RNAs is enhanced by their poly(A) tails. Hepatitis C virus (HCV) contains a positive-stranded RNA genome which does not have a poly(A) tail but has a stretch of 98 nucleotides (X region) at the 3′-untranslated region (UTR), which assumes a highly conserved stem-loop structure. This X region binds a polypyrimidine tract-binding protein (PTB), which also binds to the internal ribosome entry site (IRES) in HCV 5′-UTR. These RNA-protein interactions may regulate its translation. We generated a set of HCV RNAs differing only in their 3′-UTRs and compared their translation efficiencies. HCV RNA containing the X region was translated three- to fivefold more than the corresponding RNAs without this region. Mutations that abolished PTB binding in the X region reduced, but did not completely abolish, enhancement in translation. The X region also enhanced translation from another unrelated IRES (from encephalomyocarditis virus RNA), but did not affect the 5′-end-dependent translation of globin mRNA in either monocistronic or bicistronic RNAs. It did not appear to affect RNA stability. The free X region added in trans, however, did not enhance translation, indicating that the translational enhancement by the X region occurs only in cis. These results demonstrate that the highly conserved 3′ end of HCV RNA provides a novel mechanism for enhancement of HCV translation and may offer a target for antiviral agents.",,"['Ito, Takayoshi', 'Tahara, Stanley M.', 'Lai, Michael M. C.']",,,,
,PMC,Coronavirus Pseudoparticles Formed with Recombinant M and E Proteins Induce Alpha Interferon Synthesis by Leukocytes,,PMC110275,,,"Transmissible gastroenteritis virus (TGEV), an enteric coronavirus of swine, is a potent inducer of alpha interferon (IFN-α) both in vivo and in vitro. Incubation of peripheral blood mononuclear cells with noninfectious viral material such as inactivated virions or fixed, infected cells leads to early and strong IFN-α synthesis. Previous studies have shown that antibodies against the virus membrane glycoprotein M blocked the IFN induction and that two viruses with a mutated protein exhibited a decreased interferogenic activity, thus arguing for a direct involvement of M protein in this phenomenon. In this study, the IFN-α-inducing activity of recombinant M protein expressed in the absence or presence of other TGEV structural proteins was examined. Fixed cells coexpressing M together with at least the minor structural protein E were found to induce IFN-α almost as efficiently as TGEV-infected cells. Pseudoparticles resembling authentic virions were released in the culture medium of cells coexpressing M and E proteins. The interferogenic activity of purified pseudoparticles was shown to be comparable to that of TGEV virions, thus establishing that neither ribonucleoprotein nor spikes are required for IFN induction. The replacement of the externally exposed, N-terminal domain of M with that of bovine coronavirus (BCV) led to the production of chimeric particles with no major change in interferogenicity, although the structures of the TGEV and BCV ectodomains markedly differ. Moreover, BCV pseudoparticles also exhibited interferogenic activity. Together these observations suggest that the ability of coronavirus particles to induce IFN-α is more likely to involve a specific, multimeric structure than a definite sequence motif.",,"['Baudoux, Pierre', 'Carrat, Charles', 'Besnardeau, Lydia', 'Charley, Bernard', 'Laude, Hubert']",,,,
,PMC,Coronavirus Transcription Early in Infection,,PMC110261,,,"We studied the accumulation kinetics of murine coronavirus mouse hepatitis virus (MHV) RNAs early in infection by using cloned MHV defective interfering (DI) RNA that contained an intergenic sequence from which subgenomic DI RNA is synthesized in MHV-infected cells. Genomic DI RNA and subgenomic DI RNA accumulated at a constant ratio from 3 to 11 h postinfection (p.i.) in the cells infected with MHV-containing DI particles. Earlier, at 1 h p.i., this ratio was not constant; only genomic DI RNA accumulated, indicating that MHV RNA replication, but not MHV RNA transcription, was active during the first hour of MHV infection. Negative-strand genomic DI RNA and negative-strand subgenomic DI RNA were first detectable at 1 and 3 h p.i., respectively, and the amounts of both RNAs increased gradually until 6 h p.i. These data showed that at 2 h p.i., subgenomic DI RNA was undergoing synthesis in the cells in which negative-strand subgenomic DI RNA was undetectable. These data, therefore, signify that negative-strand genomic DI RNA, but not negative-strand subgenomic DI RNA, was an active template for subgenomic DI RNA synthesis early in infection.",,"['An, Sungwhan', 'Maeda, Akihiko', 'Makino, Shinji']",,,,
,PMC,The RafC1 Cysteine-Rich Domain Contains Multiple  Distinct Regulatory Epitopes Which Control  Ras-Dependent Raf Activation,,PMC109253,,,"Activation of c-Raf-1 (referred to as Raf) by Ras is a pivotal step in mitogenic signaling. Raf activation is initiated by binding of Ras to the regulatory N terminus of Raf. While Ras binding to residues 51 to 131 is well understood, the role of the RafC1 cysteine-rich domain comprising residues 139 to 184 has remained elusive. To resolve the function of the RafC1 domain, we have performed an exhaustive surface scanning mutagenesis. In our study, we defined a high-resolution map of multiple distinct functional epitopes within RafC1 that are required for both negative control of the kinase and the positive function of the protein. Activating mutations in three different epitopes enhanced Ras-dependent Raf activation, while only some of these mutations markedly increased Raf basal activity. One contiguous inhibitory epitope consisting of S177, T182, and M183 clearly contributed to Ras-Raf binding energy and represents the putative Ras binding site of the RafC1 domain. The effects of all RafC1 mutations on Ras binding and Raf activation were independent of Ras lipid modification. The inhibitory mutation L160A is localized to a position analogous to the phorbol ester binding site in the protein kinase C C1 domain, suggesting a function in cofactor binding. Complete inhibition of Ras-dependent Raf activation was achieved by combining mutations K144A and L160A, which clearly demonstrates an absolute requirement for correct RafC1 function in Ras-dependent Raf activation.",,"['Daub, Martina', 'Jöckel, Johannes', 'Quack, Thomas', 'Weber, Christoph K.', 'Schmitz, Frank', 'Rapp, Ulf R.', 'Wittinghofer, Alfred', 'Block, Christoph']",,,,
,PMC,"The association of titers to Haemophilus somnus, and other putative pathogens, with the occurrence of bovine respiratory disease and weight gain in feedlot calves.",,PMC1189492,,,"Serum samples were obtained from 602 calves (from 19 groups in four feedlots: three in Ontario, and one in Alberta) upon arrival at the feedlot and 28 d later. Of these calves, 202 developed bovine respiratory disease (BRD) and 400 did not develop BRD. Based on high antibody titers noted upon arrival, we infer that most calves were exposed to Haemophilus somnus prior to arrival at the feedlot. Within a group, calves with high titers on arrival had a reduced risk of developing BRD later. Most calves did not experience titer increases after arrival; however, calves that had stable or increasing titers had a relatively low risk of contracting BRD. The calves at greatest risk of BRD were those with titers on arrival of less than 6.8 units and subsequent titer decreases of more than 1 unit. The effects of both the titer on arrival and the titer change after arrival were stable when the serologic effects of a number of viruses and Mycoplasma agents were considered. Neither antibody titer on arrival nor titer change was related to weight gain differences among calves. Calves with BRD or calves with lower weight on arrival had decreased weight gains in the first 28-day feeding period. The high titers on arrival may have protected most calves against further infection with H. somnus. However, since the calves that developed BRD had large titer increases to a number of viruses and to Pasteurella haemolytica, while having decreased antibody titers to H. somnus, we infer that the existing antibodies were ""used up"" in combatting the agents, including H. somnus, which may have ""caused"" the BRD. Calves which were able to increase their antibody levels to H. somnus tended to have a reduced risk of BRD.",,"['Martin, S W', 'Harland, R J', 'Bateman, K G', 'Nagy, E']",,,,
,PMC,The association of titers to bovine coronavirus with treatment for bovine respiratory disease and weight gain in feedlot calves.,,PMC1189491,,,"The association between bovine respiratory disease (BRD) and antibody titers to bovine coronavirus (BCV) was studied in 604 calves (19 different groups in 4 different feedlots from 2 provinces). Almost all calves had antibody titers on arrival in the Alberta feedlot and 82% of the calves had an antibody titer on arrival at the Ontario feedlots; titers in calves in Alberta were almost twice as high as those in calves in Ontario. The incidence of infection, in the first mo after arrival as judged by seroconversion, ranged from 61% to 100%; titer increases were much greater in calves in Ontario feedlots. Titer variables were not significantly related to BRD, except on a within-group basis (group was a confounding variable for BCV-BRD associations). Given control of group effects, calves with an antibody titer on arrival appeared to be protected against BRD for the first 28 d in the feedlot, and the association was reasonably linear over the range of titers. Each titer unit on arrival decreased the risk of BRD by about 0.8x (odds ratio). Titer change was not strongly related to the risk of BRD and the relationship was not linear over the range of titer changes. Titer change was strongly and negatively correlated with titer on arrival, and titer change was not significantly related to BRD in the presence of arrival titers. Arrival titer retained its relationship with BRD in the presence of titer data for other putative pathogens. Each higher unit of titer to BCV on arrival increased the 28-day weight gain (controlling for group, initial weight and the occurrence of BRD) by slightly more than 1 kg. Titer change was associated with decreased weight gain, when initial titer was not in the model. The lack of a linear or multivariable association between BCV titer change and BRD, and weight gain, may indicate that BCV is not a major pathogen; or, its lack of significance may merely be due to its strong correlation with arrival titer. Given the associations found in this study, particularly the interprovincial differences in arrival titers, more and different approaches to studying the possible effects of BCV on BRD are in order.",,"['Martin, S W', 'Nagy, E', 'Shewen, P E', 'Harland, R J']",,,,
,PMC,trans-Encapsidation of a Poliovirus Replicon by Different Picornavirus Capsid Proteins,,PMC110132,,,"A trans-encapsidation assay was established to study the specificity of picornavirus RNA encapsidation. A poliovirus replicon with the luciferase gene replacing the capsid protein-coding region was coexpressed in transfected HeLa cells with capsid proteins from homologous or heterologous virus. Successful trans-encapsidation resulted in assembly and production of virions whose replication, upon subsequent infection of HeLa cells, was accompanied by expression of luciferase activity. The amount of luciferase activity was proportional to the amount of trans-encapsidated virus produced from the cotransfection. When poliovirus capsid proteins were supplied in trans, >2 × 10(6) infectious particles/ml were produced. When coxsackievirus B3, human rhinovirus 14, mengovirus, or hepatitis A virus (HAV) capsid proteins were supplied in trans, all but HAV showed some encapsidation of the replicon. The overall encapsidation efficiency of the replicon RNA by heterologous capsid proteins was significantly lower than when poliovirus capsid was used. trans-encapsidated particles could be completely neutralized with specific antisera against each of the donor virus capsids. The results indicate that encapsidation is regulated by specific viral nucleic acid and protein sequences.",,"['Jia, Xi-Yu', 'Van Eden, Marc', 'Busch, Marc G.', 'Ehrenfeld, Ellie', 'Summers, Donald F.']",,,,
,PMC,Importance of the Positive-Strand RNA Secondary Structure of a Murine Coronavirus Defective Interfering RNA Internal Replication Signal in Positive-Strand RNA Synthesis,,PMC110123,,,"The RNA elements that are required for replication of defective interfering (DI) RNA of the JHM strain of mouse hepatitis virus (MHV) consist of three discontinuous genomic regions: about 0.46 to 0.47 kb from both terminal sequences and an internal 58-nucleotide (nt)-long sequence (58-nt region) present at about 0.9 kb from the 5′ end of the DI genome. The internal region is important for positive-strand DI RNA synthesis (Y. N. Kim and S. Makino, J. Virol. 69:4963–4971, 1995). We further characterized the 58-nt region in the present study and obtained the following results. (i) The positive-strand RNA structure in solution was comparable with that predicted by computer modeling. (ii) Positive-strand RNA secondary structure, but not negative-strand RNA structure, was important for the biological function of the region. (iii) The biological function had a sequence-specific requirement. We discuss possible mechanisms by which the internal cis-acting signal drives MHV positive-strand DI RNA synthesis.",,"['Repass, John F.', 'Makino, Shinji']",,,,
,PMC,Analysis of Constructed E Gene Mutants of Mouse Hepatitis Virus Confirms a Pivotal Role for E Protein in Coronavirus Assembly,,PMC110113,,,"Expression studies have shown that the coronavirus small envelope protein E and the much more abundant membrane glycoprotein M are both necessary and sufficient for the assembly of virus-like particles in cells. As a step toward understanding the function of the mouse hepatitis virus (MHV) E protein, we carried out clustered charged-to-alanine mutagenesis on the E gene and incorporated the resulting mutations into the MHV genome by targeted recombination. Of the four possible clustered charged-to-alanine E gene mutants, one was apparently lethal and one had a wild-type phenotype. The two other mutants were partially temperature sensitive, forming small plaques at the nonpermissive temperature. Revertant analyses of these two mutants demonstrated that the created mutations were responsible for the temperature-sensitive phenotype of each and provided support for possible interactions among E protein monomers. Both temperature-sensitive mutants were also found to be markedly thermolabile when grown at the permissive temperature, suggesting that there was a flaw in their assembly. Most significantly, when virions of one of the mutants were examined by electron microscopy, they were found to have strikingly aberrant morphology in comparison to the wild type: most mutant virions had pinched and elongated shapes that were rarely seen among wild-type virions. These results demonstrate an important, probably essential, role for the E protein in coronavirus morphogenesis.",,"['Fischer, Françoise', 'Stegen, Carola F.', 'Masters, Paul S.', 'Samsonoff, William A.']",,,,
,PMC,Characterization of and Functional Antigen Presentation by Central Nervous System Mononuclear Cells from Mice Infected with Theiler’s Murine Encephalomyelitis Virus,,PMC110086,,,"We examined the phenotype and function of cells infiltrating the central nervous system (CNS) of mice persistently infected with Theiler’s murine encephalomyelitis virus (TMEV) for evidence that viral antigens are presented to T cells within the CNS. Expression of major histocompatibility complex (MHC) class II in the spinal cords of mice infected with TMEV was found predominantly on macrophages in demyelinating lesions. The distribution of I-A(s) staining overlapped that of the macrophage marker sialoadhesin in frozen sections and coincided with that of another macrophage/microglial cell marker, F4/80, by flow cytometry. In contrast, astrocytes, identified by staining with glial fibrillary acidic protein, rarely expressed detectable MHC class II, although fibrillary gliosis associated with the CNS damage was clearly seen. The costimulatory molecules B7-1 and B7-2 were expressed on the surface of most MHC class II-positive cells in the CNS, at levels exceeding those found in the spleens of the infected mice. Immunohistochemistry revealed that B7-1 and B7-2 colocalized on large F4/80(+) macrophages/microglia in the spinal cord lesions. In contrast, CD4(+) T cells in the lesions expressed mainly B7-2, which was found primarily on blastoid CD4(+) T cells located toward the periphery of the lesions. Most interestingly, plastic-adherent cells freshly isolated from the spinal cords of TMEV-infected mice were able to process and present TMEV and horse myoglobin to antigen-specific T-cell lines. Furthermore, these cells were able to activate a TMEV epitope-specific T-cell line in the absence of added antigen, providing conclusive evidence for the endogenous processing and presentation of virus epitopes within the CNS of persistently infected SJL/J mice.",,"['Pope, Jonathan G.', 'Vanderlugt, Carol L.', 'Rahbe, Sandra M.', 'Lipton, Howard L.', 'Miller, Stephen D.']",,,,
,PMC,Targeting of active sialyltransferase to the plant Golgi apparatus.,,PMC143948,,,"Glycosyltransferases in the Golgi apparatus synthesize cell wall polysaccharides and elaborate the complex glycans of glycoproteins. To investigate the targeting of this type of enzyme to plant Golgi compartments, we generated transgenic Arabidopsis plants expressing alpha-2,6-sialyltransferase, a glycosyltransferase of the mammalian trans-Golgi cisternae and the trans-Golgi network. Biochemical analysis as well as immunolight and immunoelectron microscopy of these plants indicate that the protein is targeted specifically to the Golgi apparatus. Moreover, the protein is predominantly localized to the cisternae and membranes of the trans side of the organelle. When supplied with the appropriate substrates, the enzyme has significant alpha-2,6-sialyltransferase activity. These results indicate a conservation of glycosyltransferase targeting mechanisms between plant and mammalian cells and also demonstrate that glycosyltransferases can be subcompartmentalized to specific cisternae of the plant Golgi apparatus.",,"['Wee, E G', 'Sherrier, D J', 'Prime, T A', 'Dupree, P']",,,,
,PMC,Immunosuppressive effect of Cryptosporidium baileyi infection on vaccination against avian infectious bronchitis in chicks,http://dx.doi.org/10.3347/kjp.1998.36.3.203,PMC2732932,,,Two-day-old commercial chicks were inoculated orally with 2 × 10(6) oocysts of Cryptosporidium baileyi and vaccinated with 10(3.5) EID(50)/head of a commercially available avian infectious bronchitis (IB) live virus vaccine at 4 and 14 days following inoculation. Chicks infected with C. baileyi were shown to have an immunosuppressive effect on IB virus. It is concluded that infection with the protozoon in early life may increase their susceptibility to IB.,,"['Rhee, Jae Ku', 'Yang, Hong Ji', 'Yook, Sim Yong', 'Kim, Hyeon Cheol']",,,,
,PMC,Detection of a Novel Strain of Porcine Circovirus in Pigs with Postweaning Multisystemic Wasting Syndrome,,PMC105158,,,"Swine infectious agents, especially viruses, are potential public health risks associated with the use of pig organs for xenotransplantation in humans. Therefore, there is a need for better characterization of swine viruses and for the development of diagnostic tests for their detection. We report here isolation of a novel strain of porcine circovirus (PCV) from pigs with postweaning multisystemic wasting syndrome (PMWS). Affected pigs exhibited severe interstitial pneumonia and lymphoid depletion. The complete nucleotide sequence (1,768 nucleotides) of the genome of the PCV isolate was determined and compared with the sequence of the PCV strain isolated from PK-15 cells. Sequence comparison revealed significant differences between the two PCV strains, with an overall DNA homology of 76%. Two major open reading frames (ORFs) were identified. ORF1 was more conserved between the two strains, with 83% nucleotide homology and 86% amino acid homology. ORF2 was more variable, with nucleotide homology of 67% and amino acid homology of 65%. PCR and in situ hybridization demonstrated abundant viral DNA in various organs of pigs with PMWS. In situ hybridization demonstrated that this strain of PCV targets multiple organs and infects macrophages, lymphocytes, endothelial cells, and epithelial cells.",,"['Morozov, Igor', 'Sirinarumitr, Theerapol', 'Sorden, Steven D.', 'Halbur, Patrick G.', 'Morgan, Marsha K.', 'Yoon, Kyoung-Jin', 'Paul, Prem S.']",,,,
,PMC,CrFK Feline Kidney Cells Produce an RD114-Like Endogenous Virus  That Can Package Murine Leukemia Virus-Based Vectors,,PMC110043,,,"The feline kidney cell line CrFK is used extensively for viral infectivity assays and for study of the biology of various retroviruses and derived vectors. We demonstrate the production of an endogenous, RD114-like, infectious retrovirus from CrFK cells. This virus also is shown to efficiently package Moloney murine leukemia virus vectors.",,"['Baumann, Jörg G.', 'Günzburg, Walter H.', 'Salmons, Brian']",,,,
,PMC,"Purified, Soluble Recombinant Mouse Hepatitis Virus Receptor, Bgp1(b), and Bgp2 Murine Coronavirus Receptors Differ in Mouse Hepatitis Virus Binding and Neutralizing Activities",,PMC109946,,,"Mouse hepatitis virus receptor (MHVR) is a murine biliary glycoprotein (Bgp1(a)). Purified, soluble MHVR expressed from a recombinant vaccinia virus neutralized the infectivity of the A59 strain of mouse hepatitis virus (MHV-A59) in a concentration-dependent manner. Several anchored murine Bgps in addition to MHVR can also function as MHV-A59 receptors when expressed at high levels in nonmurine cells. To investigate the interactions of these alternative MHVR glycoproteins with MHV, we expressed and purified to apparent homogeneity the extracellular domains of several murine Bgps as soluble, six-histidine-tagged glycoproteins, using a baculovirus expression system. These include MHVR isoforms containing four or two extracellular domains and the corresponding Bgp1(b) glycoproteins from MHV-resistant SJL/J mice, as well as Bgp2 and truncation mutants of MHVR and Bgp1(b) comprised of the first two immunoglobulin-like domains. The soluble four-domain MHVR glycoprotein (sMHVR[1-4]) had fourfold more MHV-A59 neutralizing activity than the corresponding soluble Bgp1(b) (sBgp1(b)) glycoprotein and at least 1,000-fold more neutralizing activity than sBgp2. Although virus binds to the N-terminal domain (domain 1), soluble truncation mutants of MHVR and Bgp1(b) containing only domains 1 and 2 bound virus poorly and had 10- and 300-fold less MHV-A59 neutralizing activity than the corresponding four-domain glycoproteins. In contrast, the soluble MHVR glycoprotein containing domains 1 and 4 (sMHVR[1,4]) had as much neutralizing activity as the four-domain glycoprotein, sMHVR[1-4]. Thus, the virus neutralizing activity of MHVR domain 1 appears to be enhanced by domain 4. The sBgp1(b)[1-4] glycoprotein had 500-fold less neutralizing activity for MHV-JHM than for MHV-A59. Thus, MHV strains with differences in S-glycoprotein sequence, tissue tropism, and virulence can differ in the ability to utilize the various murine Bgps as receptors.",,"['Zelus, Bruce D.', 'Wessner, David R.', 'Williams, Richard K.', 'Pensiero, Michael N.', 'Phibbs, Fenna T.', 'deSouza, Mark', 'Dveksler, Gabriela S.', 'Holmes, Kathryn V.']",,,,
,PMC,Resistance to Murine Hepatitis Virus Strain 3 Is Dependent on Production of Nitric Oxide,,PMC109929,,,"The strain-specific spectrum of liver disease following murine hepatitis virus type 3 (MHV-3) infection is dependent on inflammatory mediators released by macrophages. Production of nitric oxide (NO) by macrophages has been implicated in resistance to a number of viruses, including ectromelia virus, vaccinia virus, and herpes simplex virus type 1. This study was undertaken to define the role of NO in MHV-3 infection. Gamma interferon-induced production of NO inhibited growth of MHV-3 in a murine macrophage cell line (RAW 264.7). Viral inhibitory activity was reproduced by the NO donor S-nitroso-N-acetyl-dl-penicillamine (SNAP), whereas N-acetyl-dl-pencillamine (NAP), an inactive analog of SNAP, had no effect. Electron microscopy studies confirmed the inhibitory effects of NO on viral replication. Peritoneal macrophages isolated from A/J mice known to be resistant to MHV-3 produced a fivefold-higher level of NO and higher levels of mRNA transcripts of inducible NO synthase in response to gamma interferon than macrophages from susceptible BALB/cJ mice. SNAP inhibited growth of MHV-3 in macrophages from both strains of mice to similar degrees. In vivo inhibition of NO by N-monomethyl-l-arginine resulted in loss of resistance to MHV-3 in A/J mice. These results collectively demonstrate a defect in the production of NO in macrophages from susceptible BALB/cJ mice and define the importance of endogenous NO in resistance to MHV-3 infection in resistant A/J mice.",,"['Pope, M.', 'Marsden, P. A.', 'Cole, E.', 'Sloan, S.', 'Fung, L. S.', 'Ning, Q.', 'Ding, J. W.', 'Leibowitz, J. L.', 'Phillips, M. J.', 'Levy, G. A.']",,,,
,PMC,Recombination in the 5′ Leader of Murine Leukemia Virus Is Accurate and Influenced by Sequence Identity with a Strong  Bias toward the Kissing-Loop Dimerization Region,,PMC109916,,,"Retroviral recombination occurs frequently during reverse transcription of the dimeric RNA genome. By a forced recombination approach based on the transduction of Akv murine leukemia virus vectors harboring a primer binding site knockout mutation and the entire 5′ untranslated region, we studied recombination between two closely related naturally occurring retroviral sequences. On the basis of 24 independent template switching events within a 481-nucleotide target sequence containing multiple sequence identity windows, we found that shifting from vector RNA to an endogenous retroviral RNA template during minus-strand DNA synthesis occurred within defined areas of the genome and did not lead to misincorporations at the crossover site. The nonrandom distribution of recombination sites did not reflect a bias for specific sites due to selection at the level of marker gene expression. We address whether template switching is affected by the length of sequence identity, by palindromic sequences, and/or by putative stem-loop structures. Sixteen of 24 sites of recombination colocalized with the kissing-loop dimerization region, and we propose that RNA-RNA interactions between palindromic sequences facilitate template switching. We discuss the putative role of the dimerization domain in the overall structure of the reverse-transcribed RNA dimer and note that related mechanisms of template switching may be found in remote RNA viruses.",,"['Mikkelsen, Jacob Giehm', 'Lund, Anders H.', 'Duch, Mogens', 'Pedersen, Finn Skou']",,,,
,PMC,Phage-displayed peptide libraries,,PMC3987777,,,"Over the past year, significant advances have been achieved through the use of phage-displayed peptide libraries. A wide variety of bioactive molecules, including antibodies, receptors and enzymes, have selected high-affinity and/or highly-specific peptide ligands from a number of different types of peptide library. The demonstrated therapeutic potential of some of these peptides, as well as new insights into protein structure and function that peptide ligands have provided, highlight the progress made within this rapidly-expanding field.",,"['Zwick, Michael B', 'Shen, Juqun', 'Scott, Jamie K']",,,,
,PMC,At-risk individuals in Feline Immunodeficiency Virus epidemiology: evidence from a multivariate approach in a natural population of domestic cats (Felis catus).,,PMC2809496,,,"Prevalence of Feline Immunodeficiency Virus (FIV) infection was measured during 6 consecutive years in a natural rural population of domestic cats. Sex, age, weight, origin, group size and presence of antibodies to FIV were recorded for each sampled cat. Logistic regressions were used to estimate the influence of the recorded parameters on infection. FIV prevalence rates are as high as 19.6% in the total population, and do not statistically change between years, after controlling for changes in samples' age structure. FIV infection is characterized by risk factors linked to aggressive behaviour: old mature male adults having dispersed are more likely to be infected. A study of the cats group size and of the spatial distribution of infected individuals indicates the absence of infection clusters in males, and suggests the importance of roaming in the spreading of FIV. In conclusion, FIV infection spreads, with low contagiousness, mainly between particularly aggressive individuals, and the virus is endemic in this population.",,"['Courchamp, F.', 'Yoccoz, N. G.', 'Artois, M.', 'Pontier, D.']",,,,
,PMC,Coronavirus Particle Assembly: Primary Structure Requirements of the Membrane Protein,,PMC109893,,,"Coronavirus-like particles morphologically similar to normal virions are assembled when genes encoding the viral membrane proteins M and E are coexpressed in eukaryotic cells. Using this envelope assembly assay, we have studied the primary sequence requirements for particle formation of the mouse hepatitis virus (MHV) M protein, the major protein of the coronavirion membrane. Our results show that each of the different domains of the protein is important. Mutations (deletions, insertions, point mutations) in the luminal domain, the transmembrane domains, the amphiphilic domain, or the carboxy-terminal domain had effects on the assembly of M into enveloped particles. Strikingly, the extreme carboxy-terminal residue is crucial. Deletion of this single residue abolished particle assembly almost completely; most substitutions were strongly inhibitory. Site-directed mutations in the carboxy terminus of M were also incorporated into the MHV genome by targeted recombination. The results supported a critical role for this domain of M in viral assembly, although the M carboxy terminus was more tolerant of alteration in the complete virion than in virus-like particles, likely because of the stabilization of virions by additional intermolecular interactions. Interestingly, glycosylation of M appeared not essential for assembly. Mutations in the luminal domain that abolished the normal O glycosylation of the protein or created an N-glycosylated form had no effect. Mutant M proteins unable to form virus-like particles were found to inhibit the budding of assembly-competent M in a concentration-dependent manner. However, assembly-competent M was able to rescue assembly-incompetent M when the latter was present in low amounts. These observations support the existence of interactions between M molecules that are thought to be the driving force in coronavirus envelope assembly.",,"['de Haan, Cornelis A. M.', 'Kuo, Lili', 'Masters, Paul S.', 'Vennema, Harry', 'Rottier, Peter J. M.']",,,,
,PMC,ORF1a-Encoded Replicase Subunits Are Involved in the Membrane Association of the Arterivirus Replication Complex,,PMC109868,,,"Among the functions of the replicase of equine arteritis virus (EAV; family Arteriviridae, order Nidovirales) are important viral enzyme activities such as proteases and the putative RNA polymerase and RNA helicase functions. The replicase is expressed in the form of two polyproteins (open reading frame 1a [ORF1a] and ORF1ab), which are processed into 12 nonstructural proteins by three viral proteases. In immunofluorescence assays, the majority of these cleavage products localized to the perinuclear region of the cell. A dense granular and vesicular staining was observed, which strongly suggested membrane association. By using confocal microscopy and double-label immunofluorescence, the distribution of the EAV replicase was shown to overlap with that of PDI, a resident protein of the endoplasmic reticulum and intermediate compartment. An in situ labeling of nascent viral RNA with bromo-UTP demonstrated that the membrane-bound complex in which the replicase subunits accumulate is indeed the site of viral RNA synthesis. A number of ORF1a-encoded hydrophobic domains were postulated to be involved in the membrane association of the arterivirus replication complex. By using various biochemical methods (Triton X-114 extraction, membrane purification, and sodium carbonate treatment), replicase subunits containing these domains were shown to behave as integral membrane proteins and to be membrane associated in infected cells. Thus, contribution to the formation of a membrane-bound scaffold for the viral replication-transcription complex appears to be an important novel function for the arterivirus ORF1a replicase polyprotein.",,"['van der Meer, Yvonne', 'van Tol, Hans', 'Krijnse Locker, Jacomine', 'Snijder, Eric J.']",,,,
,PMC,"Moloney Murine Leukemia Virus Envelope Protein Subunits, gp70 and Pr15E, Form a Stable Disulfide-Linked Complex",,PMC109824,,,"The nature and stability of the interactions between the gp70 and Pr15E/p15E molecules of murine leukemia virus (MLV) have been disputed extensively. To resolve this controversy, we have performed quantitative biochemical analyses on gp70-Pr15E complexes formed after independent expression of the amphotropic and ecotropic Moloney MLV env genes in BHK-21 cells. We found that all cell-associated gp70 molecules are disulfide linked to Pr15E whereas only a small amount of free gp70 is released by the cells. The complexes were resistant to treatment with reducing agents in vivo, indicating that the presence and stability of the disulfide interaction between gp70 and Pr15E are not dependent on the cellular redox state. However, disulfide-bonded Env complexes were disrupted in lysates of nonalkylated cells in a time-, temperature-, and pH-dependent fashion. Disruption seemed not to be caused by a cellular factor but is probably due to a thiol-disulfide exchange reaction occurring within the Env complex after solubilization. The possibility that alkylating agents induce the formation of the intersubunit disulfide linkage was excluded by showing that disulfide-linked gp70-Pr15E complexes exist in freshly made lysates of nonalkylated cells and that disruption of the complexes can be prevented by lowering the pH. Together, these data establish that gp70 and Pr15E form a stable disulfide-linked complex in vivo.",,"['Opstelten, Dirk-Jan E.', 'Wallin, Michael', 'Garoff, Henrik']",,,,
,PMC,Involvement of Aminopeptidase N (CD13) in Infection of Human Neural Cells by Human Coronavirus 229E,,PMC109818,,,"Attachment to a cell surface receptor can be a major determinant of virus tropism. Previous studies have shown that human respiratory coronavirus HCV-229E uses human aminopeptidase N (hAPN [CD13]) as its cellular receptor for infection of lung fibroblasts. Although human coronaviruses are recognized respiratory pathogens, occasional reports have suggested their possible neurotropism. We have previously shown that human neural cells, including glial cells in primary cultures, are susceptible to human coronavirus infection in vitro (A. Bonavia, N. Arbour, V. W. Yong, and P. J. Talbot, J. Virol. 71:800–806, 1997). However, the only reported expression of hAPN in the nervous system is at the level of nerve synapses. Therefore, we asked whether hAPN is utilized as a cellular receptor for infection of these human neural cell lines. Using flow cytometry, we were able to show the expression of hAPN on the surfaces of various human neuronal and glial cell lines that are susceptible to HCV-229E infection. An hAPN-specific monoclonal antibody (WM15), but not control antibody, inhibited the attachment of radiolabeled HCV-229E to astrocytic, neuronal, and oligodendrocytic cell lines. A correlation between the apparent amount of cell surface hAPN and the level of virus attachment was observed. Furthermore, the presence of WM15 inhibited virus infection of these cell lines, as detected by indirect immunofluorescence. These results indicate that hAPN (CD13) is expressed on neuronal and glial cell lines in vitro and serves as the receptor for infection by HCV-229E. This further strengthens the neurotropic potential of this human respiratory virus.",,"['Lachance, Claude', 'Arbour, Nathalie', 'Cashman, Neil R.', 'Talbot, Pierre J.']",,,,
,PMC,Intestinal Intraepithelial Lymphocytes Are Primed for Gamma Interferon and MIP-1β Expression and Display Antiviral Cytotoxic Activity despite Severe CD4(+) T-Cell Depletion in Primary Simian Immunodeficiency Virus Infection,,PMC109797,,,"Intraepithelial lymphocytes (IEL) are a critical effector component of the gut-associated lymphoid tissue (GALT) and play an important role in mucosal immunity as well as in the maintenance of the epithelial cell integrity and barrier function. The objective of this study was to determine whether simian immunodeficiency virus (SIV) infection of rhesus macaques would cause alterations in the immunophenotypic profiles of IEL and their mitogen-specific cytokine (gamma interferon [IFN-γ] and MIP-1β) responses (by flow cytometry) and virus-specific cytotoxic T-cell (CTL) activity (by the chromium release assay). Virally infected IEL were detected through the entire course of SIV infection by in situ hybridization. Severe depletion of CD4(+) single-positive and CD4(+)CD8(+) double-positive T cells occurred early in primary SIV infection, which was coincident with an increased prevalence of CD8(+) T cells. This was in contrast to a gradual depletion of CD4(+) T cells in peripheral blood. The CD8(+) IEL were the primary producers of IFN-γ and MIP-1β and were found to retain their potential to produce both IFN-γ and MIP-1β through the entire course of SIV infection. SIV-specific CTL activity was detected in primary IEL at 1, 2, and 4 weeks post-SIV infection. These results demonstrated that IEL may be involved in generating antiviral immune responses early in SIV infection and in suppressing viral infection thereafter. Alterations in homeostasis in epithelia due to severe CD4(+) T-cell depletion accompanied by changes in the cytokine and chemokine production by IEL may play a role in the enteropathogenesis of SIV infection.",,"['Mattapallil, Joseph J.', 'Smit-McBride, Zeljka', 'McChesney, Michael', 'Dandekar, Satya']",,,,
,PMC,A Subset of Porcine Reproductive and Respiratory Syndrome Virus GP(3) Glycoprotein Is Released into the Culture  Medium of Cells as a Non-Virion-Associated  and Membrane-Free (Soluble) Form,,PMC109768,,,"The GP(3) protein of the IAF-Klop strain of porcine reproductive and respiratory syndrome virus (PRRSV) was expressed in 293 cells by a recombinant human type 5 adenovirus carrying the open reading frame 3 gene. The protein exhibited a molecular mass of 42 kDa and comigrated with GP(3) expressed in PRRSV-infected MARC-145 cells. Removal of N-linked glycans from GP(3) resulted in a 27-kDa protein (P3), confirming its highly glycosylated nature. Pulse-chase experiments carried out either in the context of PRRSV infection or upon individual expression of GP(3) in 293 cells showed that the protein remains completely endo-β-N-acetylglucosaminidase H-sensitive even after 4 h of synthesis. Thus, the transport of GP(3) was restricted to the premedial Golgi compartment, presumably the endoplasmic reticulum (ER). However, a minor fraction of GP(3) was found to be secreted in the culture medium as a soluble membrane-free form. This released protein (sGP(3)) was readily identified upon individual expression of GP(3) in 293 cells as well as in the context of PRRSV infection, albeit at lower levels. The sGP(3) migrated as a smear and displayed a molecular mass ranging from 43 to 53 kDa. The unglycosylated form of sGP(3) comigrated with its intracellular deglycosylated counterpart, suggesting that the release from the cell of a subset of GP(3) did not result from cleavage of a putative membrane-anchor sequence. Strikingly, unlike GP(3), the sGP(3) acquired Golgi-specific modifications of its carbohydrate side chains and folded into a disulfide-linked homodimer. Brefeldin A treatment completely abolished the release of sGP(3), suggesting that the ER-to-Golgi compartment is an obligatory step in cellular secretion of sGP(3). In contrast, 10 mM monensin did not prevent sGP(3) release but inhibited the terminal glycosylation that confers on the protein its diffuse pattern. Since GP(3) was found to be nonstructural in the case of the North American strain, secretion of a minor fraction of GP(3) might be an explanation for its high degree of immunogenicity in infected pigs. Furthermore, this secreted protein might be relevant as a model for further studies on the cellular subcompartments involved in the sorting of proteins to the extracellular milieu.",,"['Mardassi, Helmi', 'Gonin, Patrick', 'Gagnon, Carl A.', 'Massie, Bernard', 'Dea, Serge']",,,,
,PMC,"Nucleotide sequence and genetic analysis of the leader region of Canadian, American and European equine arteritis virus isolates.",,PMC1189480,,,"The extreme 5' end, the entire leader sequence of the Arvac vaccine strain, and 10 equine arteritis virus (EAV) isolates, including the ATCC Bucyrus reference strain and 5 Canadian field isolates, were determined and compared at the primary nucleotide and secondary structure levels. The leader sequence of eight EAV isolates, including the Bucyrus reference strain, and the leader sequence of the Arvac vaccine strain was determined to be 206 nt in length (not including the putative 5' cap structure-associated nucleotide) whereas those of the 86AB-A1 and 86NY-A1 isolates were found to be 205 and 207 nt in length, respectively. The sequence identity of the leader sequences, between the different isolates and the Bucyrus reference strain, ranged from 94.2 to 98.5%. Phylogenetic analysis and estimation of genetic distances, based on the leader nucleic acid sequences, showed that all EAV isolates/strains are likely to represent a large phylogenetically-related group. An AUG start codon found at position 14 in all EAV isolates/strains could initiate an open reading frame (ORF) that could produce a polypeptide of 37 amino acids, except for the 86NY-A1 isolate where the intraleader polypeptide would contain 54 amino acids. Computer-predicted RNA secondary structures were identified in the 11 EAV leader regions analyzed. All EAV isolates/strains showed 3 conserved stem-loops (designated A, B and C). An additional conserved stem-loop (D) was observed in 7 EAV isolates, including the Bucyrus reference strain. The leader region distal to stem-loop D did not contain conserved sequences or stem-loop structures common to the EAV isolates/strains.",,"['Kheyar, A', 'St-Laurent, G', 'Diouri, M', 'Archambault, D']",,,,
,PMC,"A reliable, practical, and economical protocol for inducing diarrhea and severe dehydration in the neonatal calf.",,PMC1189477,,,"Fifteen healthy, colostrum-fed, male dairy calves, aged 2 to 7 d were used in a study to develop a diarrhea protocol for neonatal calves that is reliable, practical, and economical. After instrumentation and recording baseline data, diarrhea and dehydration were induced by administering milk replacer [16.5 mL/kg of body weight (BW), PO], sucrose (2 g/kg in a 20% aqueous solution, p.o.), spironolactone and hydrochlorothiazide (1 mg/kg, PO) every 8 h, and furosemide (2 mg/kg, i.m., q6h). Calves were administered sucrose and diuretic agents for 48 h to induce diarrhea and severe dehydration. Clinical changes after 48 h were severe watery diarrhea, severe depression, and marked dehydration (mean, 14% BW loss). Cardiac output, stroke volume, mean central venous pressure, plasma volume, thiocyanate space, blood pH and bicarbonate concentration, base excess, serum chloride concentration, and fetlock temperature were decreased. Plasma lactate concentration, hematocrit, and serum potassium, creatinine, phosphorus, total protein and albumin concentrations were increased. This non-infectious calf diarrhea protocol has a 100% response rate, while providing a consistent and predictable hypovolemic state with diarrhea that reflects most of the clinicopathologic changes observed in osmotic/maldigestive diarrhea caused by infection with rotavirus, coronavirus or cryptosporidia. Limitations of the protocol, when compared to infectious diarrhea models, include failure to induce a severe metabolic acidosis, absence of hyponatremia, renal instead of enteric loss of chloride, renal as well as enteric loss of free water, absence of profound clinical depression and suspected differences in the morphologic and functional effect on intestinal epithelium. Despite these differences, the sucrose/diuretic protocol should be useful in the initial screening of new treatment modalities for calf diarrhea. To confirm their efficacy, the most effective treatment methods should then be examined in calves with naturally-acquired diarrhea.",,"['Walker, P G', 'Constable, P D', 'Morin, D E', 'Drackley, J K', 'Foreman, J H', 'Thurmon, J C']",,,,
,PMC,Vaccination of dogs and cats: general principles and duration of immunity.,,PMC1539523,,,,,"['Kruth, S A', 'Ellis, J A']",,,,
,PMC,Interpretations of Antibody Responses to Salmonella enterica Serotype Enteritidis gm Flagellin in Poultry Flocks Are Enhanced by a Kinetics-Based Enzyme-Linked Immunosorbent Assay,,PMC95616,,,"Many regulatory and diagnostic programs for the detection of Salmonella enterica serotype Enteritidis infection in commercial poultry flocks have relied on rapid Pullorum agglutination tests to screen birds because of the shared antigens of S. enterica Enteritidis and S. enterica Pullorum and Gallinarum; however, the use of the enzyme-linked immunosorbent assay (ELISA) format affords better analytical sensitivity than crude agglutination tests. In this study, we adapted our earlier conventional indirect ELISA, using gm flagellin as the antigen, to a kinetics-based, computer-controlled ELISA (KELA). The KELA was used to screen for flagellin antibody from three commercial flocks: (i) a large flock involved in a U.S. Department of Agriculture trace back from a human S. enterica Enteritidis foodborne outbreak (n = 3,209), (ii) a flock infected with the endemic S. enterica Enteritidis serotype but which also had multiple other salmonella serotypes (n = 65), and (iii) an S. enterica Pullorum-infected flock (n = 12). The first flock (S. enterica Enteritidis prevalence of 2.45% based on culture) provided a field test of the KELA and allowed the calculation of diagnostic sensitivity (D-Sn) and diagnostic specificity (D-Sp). With a cutoff of 10 (used for screening flocks [i.e., high sensitivity]), the KELA has a D-Sn of 95.2% and a D-Sp of 18.5%; with a cutoff of 140 (used in confirmatory flock testing [i.e., high specificity]), the KELA has a D-Sn of 28.0% and a D-Sp of 99.1%. We found that with a cutoff of 60 (D-Sn = 63.1%; D-Sp = 91.6%), we could eliminate reactions in the KELA caused by other non-S. enterica Enteritidis salmonellae. The KELA was also compared to two commercial rapid Pullorum tests, the Solvay (D-Sn = 94.9%; D-Sp = 55.5%) and the Vineland (D-Sn = 62.0%; D-Sp = 75.3%).",,"['McDonough, Patrick L.', 'Jacobson, Richard H.', 'Timoney, John F.', 'Mutalib, Ahmed', 'Kradel, David C.', 'Chang, Yung-fu', 'Shin, Sang J.', 'Lein, Donald H.', 'Trock, Susan', 'Wheeler, Kaye']",,,,
,PMC,"Inducible Nitric Oxide Synthase and Nitrotyrosine Are Found in Monocytes/Macrophages and/or Astrocytes in Acute, but  Not in Chronic, Multiple Sclerosis",,PMC95596,,,"We have examined the localization of inducible nitric oxide synthase (iNOS) and nitrotyrosine (the product of nitration of tyrosine by peroxynitrite, a highly reactive derivative of nitric oxide [NO]) in demyelinating lesions from (i) two young adult patients with acute multiple sclerosis (MS), (ii) a child with MS (consistent with diffuse sclerosis), and (iii) five adult patients with chronic MS. Previous reports have suggested a possible correlation between iNOS, peroxynitrite, related nitrogen-derived oxidants, and the demyelinating processes in MS. We have demonstrated iNOS-immunoreactive cells in both acute-MS and diffuse-sclerosis-type lesions. In acute-MS lesions, iNOS was localized in both monocytes/macrophages and reactive astrocytes. However, foamy (myelin-laden) macrophages and the majority of reactive astrocytes were iNOS negative. In specimens from the childhood MS patient, iNOS protein was present only in a subpopulation of reactive or hypertrophic astrocytes. In contrast, no iNOS staining was detected in chronic-MS lesions. Immunohistochemical staining of acute-MS lesions with an antibody to nitrotyrosine revealed codistribution of iNOS- and nitrotyrosine-positive cells, although nitrotyrosine staining was more widespread in cells of the monocyte/macrophage lineage. In diffuse-sclerosis-type lesions, nitrotyrosine staining was present in hypertrophic astrocytes, whereas it was absent in chronic-MS lesions. These results suggest that NO and nitrogen-derived oxidants may play a role in the initiation of demyelination in acute-MS lesions but not in the later phase of the disease.",,"['Oleszak, Emilia L.', 'Zaczynska, Ewa', 'Bhattacharjee, Meena', 'Butunoi, Catalin', 'Legido, Agustin', 'Katsetos, Christos D.']",,,,
,PMC,Molecular approach to find target(s) for oligoclonal bands in multiple sclerosis,,PMC2170146,,,"OBJECTIVES—Oligoclonal bands are a characteristic finding in the CSF of patients with multiple sclerosis, yet their target antigen(s) remain unknown. The objective was to determine whether a filamentous phage peptide library could be employed to allow the oligoclonal bands to select their own target epitopes.
METHODS—CSF IgG antibody from 14 patients with multiple sclerosis and 14 controls was used to select individual phage clones from a bacteriophage library containing≈4 × 10(7) different hexamers expressed on its surface pIII protein. The amino acid sequence selected was deduced by sequencing the DNA of the genetically engineered insert.
RESULTS—In general, after three rounds of selection, CSF from both patients with multiple sclerosis and controls selected one to two consistent peptide motifs. Five out of 14 patients with multiple sclerosis, and one control, selected the amino acid sequence motif, RRPFF. Given 20 possible amino acids per position, the likelihood of five patients selecting the same linear five amino acid sequence is at most 1.6 × 10(-13), corrected for the number of clones sequenced. A GenBank computer search showed that this sequence is found in the Epstein-Barr Virus nuclear antigen (EBNA-1), and a heat shock protein αB crystallin. Human serum antibodies to a synthetic peptide containing RRPFF were virtually exclusively found in patients with prior infection by Epstein-Barr virus. Other studies have suggested a relation between Epstein-Barr virus infection and multiple sclerosis, including nearly 100% Epstein-Barr virus seropositivity among patients with multiple sclerosis and increased concentrations of antibody to EBNA in CSF of patients with multiple sclerosis. By antigen specific immunoblotting, antibodies to the RRPFF motif in the CSF were shown to correspond to a subset of oligoclonal bands in the CSF from the same patient.
CONCLUSION—This study shows that phage epitope display libraries may be used to select amino acid motifs which are potentially relevant to the pathogenesis of multiple sclerosis.",,"['Rand, K.', 'Houck, H.', 'Denslow, N.', 'Heilman, K.']",,,,
,PMC,Novel Gag-Pol Frameshift Site in Human Immunodeficiency Virus Type 1 Variants Resistant to Protease Inhibitors,,PMC110421,,,"Human immunodeficiency virus type 1 (HIV-1) variants resistant to protease inhibitors have been shown to contain a mutation in the p1/p6 Gag precursor cleavage site. At the messenger RNA level, this mutation generates a U UUU UUU sequence that is reminiscent of the U UUU UUA sequence required for ribosomal frameshifting and Gag-Pol synthesis. To test whether the p1/p6 cleavage site mutation was generating a novel frameshift site, HIV sequences were inserted in translation vectors containing a chloramphenicol acetyltransferase (CAT) reporter gene requiring −1 frameshifting for expression. All sequences containing the original HIV frameshift site supported the synthesis of CAT but expression was increased 3- to 11-fold in the presence of the mutant p1/p6 sequence. When the original frameshift site was abolished by mutation, expression remained unchanged when using constructs containing the mutant p1/p6 sequence, whereas it was decreased 2- to 4.5-fold when using wild-type p1/p6 constructs. Similarly, when introduced into HIV molecular clones, the p1/p6 mutant sequence supported Gag-Pol synthesis and protease activity in the absence of the original frameshift site, indicating that this sequence could also promote ribosomal frameshifting in virus-expressing cells.",,"['Doyon, Louise', 'Payant, Catherine', 'Brakier-Gingras, Léa', 'Lamarre, Daniel']",,,,
,PMC,Infection with Cytotoxic T-Lymphocyte Escape Mutants Results in Increased Mortality and Growth Retardation in Mice Infected with a Neurotropic Coronavirus,,PMC110395,,,"C57BL/6 mice infected with mouse hepatitis virus strain JHM (MHV-JHM) develop a chronic demyelinating encephalomyelitis several weeks after inoculation. Previously, we showed that mutations in the immunodominant CD8 T-cell epitope (S-510-518) could be detected in nearly all samples of RNA and virus isolated from these mice. These mutations abrogated recognition by T cells harvested from the central nervous systems of infected mice in direct ex vivo cytotoxicity assays. These results suggested that cytotoxic T-lymphocyte (CTL) escape mutants contributed to virus amplification and the development of clinical disease in mice infected with wild-type virus. In the present study, the importance of these mutations was further evaluated by infecting naive mice with MHV-JHM variants isolated from infected mice and in which epitope S-510-518 was mutated. Compared to mice infected with wild-type virus, variant virus-infected animals showed higher mortality and morbidity manifested by decreased weight gain and neurological signs. Although a delay in the kinetics of virus clearance has been demonstrated in previous studies of CTL escape mutants, this is the first illustration of significant changes in clinical disease resulting from infection with viruses able to evade the CD8 T-cell immune response.",,"['Pewe, Lecia', 'Xue, Shurong', 'Perlman, Stanley']",,,,
,PMC,Genes Required for Replication of the 15.5-Kilobase RNA Genome of a Plant Closterovirus,,PMC110390,,,"A full-length cDNA clone of beet yellows closterovirus (BYV) was engineered and used to map functions involved in the replication of the viral RNA genome and subgenomic RNA formation. Among 10 open reading frames (ORFs) present in BYV, ORFs 1a and 1b suffice for RNA replication and transcription. The proteins encoded in these ORFs harbor putative methyltransferase, RNA helicase, and RNA polymerase domains common to Sindbis virus-like viruses and a large interdomain region that is unique to closteroviruses. The papain-like leader proteinase (L-Pro) encoded in the 5′-proximal region of ORF 1a was found to have a dual function in genome amplification. First, the autocatalytic cleavage between L-Pro and the remainder of the ORF 1a product was essential for replication of RNA. Second, an additional L-Pro function that was separable from proteolytic activity was required for efficient RNA accumulation. The deletion of a large, ∼5.6-kb, 3′-terminal region coding for a 6-kDa hydrophobic protein, an HSP70 homolog, a 64-kDa protein, minor and major capsid proteins, a 20-kDa protein, and a 21-kDa protein (p21) resulted in replication-competent RNA. However, examination of mutants with replacements of start codons in each of these seven 3′-terminal ORFs revealed that p21 functions as an enhancer of genome amplification. The intriguing analogies between the genome organization and replicational requirements of plant closteroviruses and animal coronavirus-like viruses are discussed.",,"['Peremyslov, Valery V.', 'Hagiwara, Yuka', 'Dolja, Valerian V.']",,,,
,PMC,Cleavage of Rhesus Rotavirus VP4 after Arginine 247 Is Essential for Rotavirus-Like Particle-Induced Fusion from Without,,PMC116396,,,"We recently described our finding that recombinant baculovirus-produced virus-like particles (VLPs) can induce cell-cell fusion similar to that induced by intact rotavirus in our assay for viral entry into tissue culture cells (J. M. Gilbert and H. B. Greenberg, J. Virol. 71:4555–4563, 1997). The conditions required for syncytium formation are similar to those for viral penetration of the plasma membrane during the course of viral infection. This VLP-mediated fusion activity was dependent on the presence of the outer-layer proteins, viral protein 4 (VP4) and VP7, and on the trypsinization of VP4. Fusion activity occurred only with cells that are permissive for rotavirus infection. Here we begin to dissect the role of VP4 in rotavirus entry by examining the importance of the precise trypsin cleavage of VP4 and the activation of VP4 function related to viral entry. We present evidence that the elimination of the three trypsin-susceptible arginine residues of VP4 by specific site-directed mutagenesis prevents syncytium formation. Two of the three arginine residues in VP4 are dispensable for syncytium formation, and only the arginine residue at site 247 appears to be required for activation of VP4 functions and cell-cell fusion. Using the recombinant VLPs in our syncytium assay will aid in understanding the conformational changes that occur in VP4 involved in rotavirus penetration into host cells.",,"['Gilbert, Joanna M.', 'Greenberg, Harry B.']",,,,
,PMC,Transmissible Gastroenteritis Coronavirus Induces Programmed Cell Death in Infected Cells through a Caspase-Dependent Pathway,,PMC110052,,,"In this report, we show that apoptosis (or programmed cell death) is induced in different cell lines infected with a coronavirus, the porcine transmissible gastroenteritis virus (TGEV). Kinetic analysis of internucleosomal DNA cleavage by agarose gel electrophoresis and flow cytometry or cytometric monitoring of the mitochondrial transmembrane potential showed that, for ST cells infected with TGEV, the first overt signs of apoptosis appeared from 10 to 12 h postinfection on. They preceded morphological changes characteristic of cells undergoing apoptosis, as observed by light and electron microscopy. The tripeptide pan-ICE (caspase) inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone blocked TGEV-induced apoptosis with no effect on virus production. The thiol agent pyrrolidine dithiocarbamate inhibited apoptosis, suggesting that TGEV infection may lead to apoptosis via cellular oxidative stress. The effect of TGEV infection on activation of NF-κB, a transcription factor known to be activated by oxidative stress, was examined. NF-κB DNA binding was shown to be strongly and quickly induced by TGEV infection. However, transcription factor decoy experiments showed that NF-κB activation is not critical for TGEV-induced apoptosis.",,"['Eleouet, Jean-François', 'Chilmonczyk, Stefan', 'Besnardeau, Lydia', 'Laude, Hubert']",,,,
,PMC,Does Nitric Oxide Play a Critical Role in Viral Infections?,,PMC109964,,,,,"['Reiss, Carol Shoshkes', 'Komatsu, Takashi']",,,,
,PMC,Immunohistochemical Detection of Porcine Epidemic Diarrhea Virus Compared to Other Methods,,PMC104535,,,"An immunohistochemistry method using formalin-fixed tissues, a direct immunofluorescence method using cryostat sections, an enzyme-linked immunosorbent assay (ELISA), and a PCR method were compared for diagnosis in a litter of weaned pigs that had been experimentally inoculated with wild-type porcine epidemic diarrhea virus (PEDV) and killed between 6 and 60 h after onset of diarrhea. The immunohistochemistry method proved to be as reliable as direct immunofluorescence for diagnosis of PEDV in tissues collected postmortem. The good reliability of ELISA for investigating clinical samples was confirmed, whereas the PCR method used was ineffective.",,"['Guscetti, Franco', 'Bernasconi, Curzio', 'Tobler, Kurt', 'Van Reeth, Kristien', 'Pospischil, Andreas', 'Ackermann, Mathias']",,,,
,PMC,Detection of Bovine Torovirus in Fecal Specimens of Calves with Diarrhea from Ontario Farms,,PMC104812,,,"Breda virus (BRV), a member of the genus Torovirus, is an established etiological agent of disease in cattle. BRV isolates have been detected in the stools of neonatal calves with diarrhea in both Iowa and Ohio and in several areas of Europe. However, this virus has been reported only once in Canada. Therefore, a study was performed to determine the extent to which bovine torovirus is present in calves with diarrhea from farms in southern Ontario. A total of 118 fecal samples from symptomatic calves and 43 control specimens from asymptomatic calves were examined by electron microscopy (EM) and reverse transcription-PCR (RT-PCR) for the presence of torovirus. Torovirus RNA was detected in 43 of the 118 diarrheic samples (36.4%) by RT-PCR with primers designed in the conserved 3′ end of the torovirus genome. By EM, torovirus particles were observed in 37 of the 118 specimens (31.4%). All but one of these samples were also positive by RT-PCR. The incidence of torovirus in the asymptomatic control specimens by RT-PCR was only 11.6%. To establish the identity of the particles observed in the diarrheic specimens, five of the amplicons from samples positive by both RT-PCR and EM were cloned and sequenced. Nucleotide sequence analysis revealed that the bovine torovirus found in southern Ontario manifests between 96 and 97% sequence identity to the BRV type 1 strain found in Iowa. This study shows that bovine torovirus is a common virus in the fecal specimens of calves with diarrhea from farms in southern Ontario and thus may be an important pathogen of cattle.",,"['Duckmanton, Lynn', 'Carman, Susy', 'Nagy, Éva', 'Petric, Martin']",,,,
,PMC,Feline Coronavirus Type II Strains 79-1683 and 79-1146 Originate from a Double Recombination between Feline Coronavirus  Type I and Canine Coronavirus,,PMC109693,,,"Recent evidence suggests that the type II feline coronavirus (FCoV) strains 79-1146 and 79-1683 have arisen from a homologous RNA recombination event between FCoV type I and canine coronavirus (CCV). In both cases, the template switch apparently took place between the S and M genes, giving rise to recombinant viruses which encode a CCV-like S protein and the M, N, 7a, and 7b proteins of FCoV type I (K. Motowaka, T. Hoh- datsu, H. Hashimoto, and H. Koyama, Microbiol. Immunol. 40:425–433, 1996; H. Vennema, A. Poland, K. Floyd Hawkins, and N. C. Pedersen, Feline Pract. 23:40–44, 1995). In the present study, we have looked for additional FCoV-CCV recombination sites. Four regions in the pol gene were selected for comparative sequence analysis of the type II FCoV strains 79-1683 and 79-1146, the type I FCoV strains TN406 and UCD1, the CCV strain K378, and the TGEV strain Purdue. Our data show that the type II FCoVs have arisen from double recombination events: additional crossover sites were mapped in the ORF1ab frameshifting region of strain 79-1683 and in the 5′ half of ORF1b of strain 79-1146.",,"['Herrewegh, Arnold A. P. M.', 'Smeenk, Ingrid', 'Horzinek, Marian C.', 'Rottier, Peter J. M.', 'de Groot, Raoul J.']",,,,
,PMC,The Rubella Virus Nonstructural Protease Requires Divalent Cations for Activity and Functions in trans,,PMC109682,,,"The rubella virus (RUB) nonstructural (NS) protease is a papain-like cysteine protease (PCP) located in the NS-protein open reading frame (NSP-ORF) that cleaves the NSP-ORF translation product at a single site to produce two products, P150 (the N-terminal product) and P90 (the C-terminal product). The RUB NS protease was found not to function following translation in vitro in a standard rabbit reticulocyte lysate system, although all of the other viral PCPs do so. However, in the presence of divalent cations such as Zn(2+), Cd(2+), and Co(2+), the RUB NS protease functioned efficiently, indicating that these cations are required either as direct cofactors in catalytic activity or for correct acquisition of three-dimensional conformation of the protease. Since other viral and cell PCPs do not require cations for activity and the RUB NS protease contains a putative zinc binding motif, the latter possibility is more likely. Previous in vivo expression studies of the RUB NS protease failed to demonstrate trans cleavage activity (J.-P. Chen et al., J. Virol. 70:4707–4713, 1996). To study whether trans cleavage could be detected in vitro, a protease catalytic site mutant and a mutant in which the C-terminal 31 amino acids of P90 were deleted were independently introduced into plasmid constructs that express the complete NSP-ORF. Cotranslation of these mutants in vitro yielded both the native and the mutated forms of P90, indicating that the protease present in the mutated construct cleaved the catalytic-site mutant precursor. Thus, RUB NS protease can function in trans.",,"['Liu, Xin', 'Ropp, Susan L.', 'Jackson, Richard J.', 'Frey, Teryl K.']",,,,
,PMC,A 68-Nucleotide Sequence within the 3′ Noncoding Region of Simian Hemorrhagic Fever Virus Negative-Strand  RNA Binds to Four MA104 Cell Proteins,,PMC109664,,,"The 3′ noncoding region (NCR) of the negative-strand RNA [3′(−)NCR RNA] of the arterivirus simian hemorrhagic fever virus (SHFV) is 209 nucleotides (nt) in length. Since this 3′ region, designated 3′(−)209, is the site of initiation of full-length positive-strand RNA and is the template for the synthesis of the 5′ leader sequence, which is found on both full-length and subgenomic mRNAs, it is likely to contain cis-acting signals for RNA synthesis and to interact with cellular and viral proteins to form replication complexes. Gel mobility shift assays showed that cellular proteins in MA104 S100 cytoplasmic extracts formed two complexes with the SHFV 3′(−)209 RNA, and results from competition gel mobility shift assays demonstrated that these interactions were specific. Four proteins with molecular masses of 103, 86, 55, and 36 kDa were detected in UV-induced cross-linking assays, and three of these proteins (103, 55, and 36 kDa) were also detected by Northwestern blotting assays. Identical gel mobility shift and UV-induced cross-linking patterns were obtained with uninfected and SHFV-infected extracts, indicating that the four proteins detected are cellular, not viral, proteins. The binding sites for the four cellular proteins were mapped to the region between nt 117 and 184 (68-nt sequence) from the 3′ end of the SHFV negative-strand RNA. This 68-nt sequence was predicted to form two stem-loops, SL4 and SL5. The 3′(−)NCR RNA of another arterivirus, lactate dehydrogenase-elevating virus C (LDV-C), competed with the SHFV 3′(−)209 RNA in competition gel mobility shift assays. UV-induced cross-linking assays showed that four MA104 cellular proteins with the same molecular masses as those that bind to the SHFV 3′(−)209 RNA also bind to the LDV-C 3′(−)NCR RNA and equine arteritis virus 3′(−)NCR RNA. However, each of these viral RNAs also bound to an additional MA104 protein. The binding sites for the MA104 cellular proteins were shown to be located in similar positions in the LDV-C 3′(−)NCR and SHFV 3′(−)209 RNAs. These data suggest that the binding sites for a set of the cellular proteins are conserved in all arterivirus RNAs and that these cell proteins may be utilized as components of viral replication complexes.",,"['Hwang, You-Kyung', 'Brinton, Margo A.']",,,,
,PMC,Deletion Analysis of a Defective Interfering Semliki Forest Virus RNA Genome Defines a Region in the nsP2 Sequence That Is Required for Efficient Packaging of the Genome into Virus Particles,,PMC109662,,,"The 1,244-nucleotide genome of Semliki Forest virus (SFV) defective interfering (DI) RNA 19 (DI-19) is coterminal with the infectious genome and contains two major deletions. One deletion removes the end of the nsP1 gene and the beginning of the nsP2 gene, and the other removes the end of the nsP2 gene, the nsP3 and nsP4 genes, and all of the structural protein genes (M. Thomson and N. J. Dimmock, Virology 199:354–365, 1994). Like all DI SFV RNAs, DI-19 contains three regions that are conserved. Region a comprises the 5′ terminus continuous with part of the nsP1 gene, region b comprises a central part of the nsP2 gene, and region c comprises the 3′ terminus and the associated untranslated region. A deletion analysis of the 265-nucleotide b region (nucleotides 679 to 943, inclusive) was undertaken to determine its role in genome replication and packaging into DI virus particles. Deleted plasmids were constructed and transcribed, and the resulting DI RNAs were transfected into SFV-infected BHK cells. Putative progeny DI virus particles that had been released into the tissue culture fluid were then serially passaged in new monolayers together with added high-multiplicity SFV, and cells and tissue culture fluids were tested for the presence of DI RNA by reverse transcription-PCR. DI RNA that had all of the b region deleted was replicated well in BHK-21 cells, as shown by the presence of large amounts of negative-sense DI RNA and an increase in the amount of positive-sense RNA in the cytoplasm, but was packaged very inefficiently, as indicated by very low amounts of DI RNA in the tissue culture fluid. The genome of a deletion mutant that retained the 3′ 224 nucleotides of region b was packaged successfully, but one that retained only the 5′ 41 nucleotides was not detected in the tissue culture fluid. These and other data suggest that nucleotides 720 to 777 of region b are of particular importance in the packaging process. This finding agrees with data obtained with Ross River virus and contrasts with the well-studied Sindbis alphavirus major packaging signal that is located within the nsP1 gene.",,"['White, Christine L.', 'Thomson, Michael', 'Dimmock, Nigel J.']",,,,
,PMC,Secondary Structures in the Capsid Protein Coding Sequence and 3′ Nontranslated Region Involved in Amplification  of the Tobacco Etch Virus Genome,,PMC109636,,,"The 3′-terminal 350 nucleotides of the tobacco etch potyvirus (TEV) genome span the end of the capsid protein (CP)-coding sequence and the 3′ nontranslated region (NTR). The CP-coding sequence within this region contains a 105-nucleotide cis-active element required for genome replication (S. Mahajan, V. V. Dolja, and J. C. Carrington, J. Virol. 70:4370–4379, 1996). To investigate the sequence and secondary structure requirements within the CP cis-active region and the 3′ NTR, a systematic linker-scanning mutagenesis analysis was done. Forty-six mutations, each with two to six nucleotide substitutions, were introduced at consecutive hexanucleotide positions in the genome of a recombinant TEV strain expressing a reporter protein (β-glucuronidase). Genome amplification activity of each mutant in the protoplast cell culture system was measured. Mutations that severely debilitated genome amplification were identified throughout the CP-coding cis-active sequence and at several distinct locations within the 3′ NTR. However, based on a computer model of RNA folding, mutations that had the most severe effects mapped to regions that were predicted to form base-paired secondary structures. Linker-scanning mutations predicted to affect either strand of a base-paired structure within the CP-coding cis-active sequence, a base-paired structure between two segments of the CP-coding cis-active sequence and a contiguous 14-nucleotide segment of the 3′ NTR, and a base-paired structure near the 3′ terminus of the 3′ NTR inactivated genome amplification. Compensatory mutations that restored base pair interactions in each of these regions restored amplification activity, although to differing levels depending on the structure restored. These data reveal that the 3′ terminus of the TEV genome consists of a series of functionally discrete sequences and secondary structures and that the CP-coding sequence and 3′ NTR are coadapted for genome amplification function through a requirement for base pair interactions.",,"['Haldeman-Cahill, Ruth', 'Daròs, José-Antonio', 'Carrington, James C.']",,,,
,PMC,Two Types of Virus-Related Particles Are Found during Transmissible Gastroenteritis Virus Morphogenesis,,PMC109630,,,"The intracellular assembly of the transmissible gastroenteritis coronavirus (TGEV) was studied in infected swine testis (ST) cells at different postinfection times by using ultrathin sections of conventionally embedded infected cells, freeze-substitution, and methods for detecting viral proteins and RNA at the electron microscopy level. This ultrastructural analysis was focused on the identification of the different viral components that assemble in infected cells, in particular the spherical, potentially icosahedral internal core, a new structural element of the extracellular infectious coronavirus recently characterized by our group. Typical budding profiles and two types of virion-related particles were detected in TGEV-infected cells. While large virions with an electron-dense internal periphery and a clear central area are abundant at perinuclear regions, smaller viral particles, with the characteristic morphology of extracellular virions (exhibiting compact internal cores with polygonal contours) accumulate inside secretory vesicles that reach the plasma membrane. The two types of virions coexist in the Golgi complex of infected ST cells. In nocodazole-treated infected cells, the two types of virions coexist in altered Golgi stacks, while the large secretory vesicles filled with virions found in normal infections are not detected in this case. Treatment of infected cells with the Golgi complex-disrupting agent brefeldin A induced the accumulation of large virions in the cisternae that form by fusion of different membranous compartments. These data, together with the distribution of both types of virions in different cellular compartments, strongly suggest that the large virions are the precursors of the small viral particles and that their transport through a functional Golgi complex is necessary for viral maturation.",,"['Risco, Cristina', 'Muntión, María', 'Enjuanes, Luis', 'Carrascosa, José L.']",,,,
,PMC,Transgenic Mice Secreting Coronavirus Neutralizing  Antibodies into the Milk,,PMC109598,,,"Ten lines of transgenic mice secreting transmissible gastroenteritis coronavirus (TGEV) neutralizing recombinant monoclonal antibodies (rMAbs) into the milk were generated. The rMAb light- and heavy-chain genes were assembled by fusing the genes encoding the variable modules of the murine MAb 6A.C3, which binds an interspecies conserved coronavirus epitope essential for virus infectivity, and a constant module from a porcine myeloma with the immunoglobulin A (IgA) isotype. The chimeric antibody led to dimer formation in the presence of J chain. The neutralization specific activity of the recombinant antibody produced in transiently or stably transformed cells was 50-fold higher than that of a monomeric rMAb with the IgG1 isotype and an identical binding site. This rMAb had titers of up to 10(4) by radioimmunoassay (RIA) and neutralized virus infectivity up to 10(4)-fold. Of 23 transgenic mice, 17 integrated both light and heavy chains, and at least 10 of them transmitted both genes to the progeny, leading to 100% of animals secreting functional TGEV neutralizing antibody during lactation. Selected mice produced milk with TGEV-specific antibody titers higher than 10(6) as determined by RIA, neutralized virus infectivity by 10(6)-fold, and produced up to 6 mg of antibody per ml. Antibody expression levels were transgene copy number independent and integration site dependent. Comicroinjection of the genomic β-lactoglobulin gene with rMAb light- and heavy-chain genes led to the generation of transgenic mice carrying the three transgenes. The highest antibody titers were produced by transgenic mice that had integrated the antibody and β-lactoglobulin genes, although the number of transgenic animals generated does not allow a definitive conclusion on the enhancing effect of β-lactoglobulin cointegration. This approach may lead to the generation of transgenic animals providing lactogenic immunity to their progeny against enteric pathogens.",,"['Sola, Isabel', 'Castilla, Joaquín', 'Pintado, Belén', 'Sánchez-Morgado, José M.', 'Whitelaw, C. Bruce A.', 'Clark, A. John', 'Enjuanes, Luis']",,,,
,PMC,Collaboration of Antibody and Inflammation in Clearance of Rabies Virus from the Central Nervous System,,PMC109593,,,"To investigate the involvement of various cellular and humoral aspects of immunity in the clearance of rabies virus from the central nervous system, (CNS), we studied the development of clinical signs and virus clearance from the CNS in knockout mice lacking either B and T cells, CD8(+) cytotoxic T cells, B cells, alpha/beta interferon (IFN-α/β) receptors, IFN-γ receptors, or complement components C3 and C4. Following intranasal infection with the attenuated rabies virus CVS-F3, normal adult mice of different genetic backgrounds developed a transient disease characterized by loss of body weight and appetite depression which peaked at 13 days postinfection (p.i.). While these animals had completely recovered by day 21 p.i., mice lacking either B and T cells or B cells alone developed a progressive disease and succumbed to infection. Mice lacking either CD8(+) T cells, IFN receptors, or complement components C3 and C4 showed no significant differences in the development of clinical signs by comparison with intact counterparts having the same genetic background. However, while infectious virus and viral RNA could be detected in normal control mice only until day 8 p.i., in all of the gene knockout mice studied except those lacking C3 and C4, virus infection persisted through day 21 p.i. Analysis of rabies virus-specific antibody production together with histological assessment of brain inflammation in infected animals revealed that clearance of CVS-F3 by 21 days p.i. correlated with both a strong inflammatory response in the CNS early in the infection (day 8 p.i.), and the rapid (day 10 p.i.) production of significant levels of virus-neutralizing antibody (VNA). These studies confirm that rabies VNA is an absolute requirement for clearance of an established rabies virus infection. However, for the latter to occur in a timely fashion, collaboration between VNA and inflammatory mechanisms is necessary.",,"['Hooper, D. Craig', 'Morimoto, Kinjiro', 'Bette, Michael', 'Weihe, Eberhard', 'Koprowski, Hilary', 'Dietzschold, Bernhard']",,,,
,PMC,Identification and Characterization of a Porcine Torovirus,,PMC109568,,,"A porcine torovirus (PoTV) was identified and characterized; it is a novel member of the genus Torovirus (family Coronaviridae, order Nidovirales), closely related to but clearly distinct from the already recognized equine torovirus (ETV) and bovine torovirus (BoTV) representatives. Immunoelectron microscopy of feces from piglets revealed elongated, 120- by 55-nm particles which were recognized by a torovirus-specific antiserum. Amplification by reverse transcriptase (RT) PCR with primers designed to detect conserved regions (on the basis of the genomes of BoTV strain Breda and ETV strain Berne) resulted in the identification of the 489-bp nucleocapsid gene, encoding a 18.7-kDa protein. The sequence identity in this region between PoTV and both ETV and BoTV was only about 68%, whereas the latter two show 81% identity. Neutralizing antibodies directed against ETV were found in sera of adult and young pigs. In all 10 herds sampled, seropositive animals were present, and 81% of randomly selected adult sows possessed antibodies. A longitudinal study with RT PCR showed that piglets shed virus in the feces for 1 or more days, starting 4 to 14 days after weaning.",,"['Kroneman, A.', 'Cornelissen, L. A. H. M.', 'Horzinek, M. C.', 'de Groot, R. J.', 'Egberink, H. F.']",,,,
,PMC,MHC-genotype of progeny influenced by parental infection.,,PMC1689024,,,"In a previous series of in vitro fertilization experiments with mice we found non-random combination of major histocompatibility complex (MHC) haplotypes in the very early embryos. Our results suggested that two selection mechanisms were operating: (i) the eggs selected specific sperm; and (ii) the second meiotic division in the eggs was influenced by the type of sperm that entered the egg. Furthermore, the proportion of MHC-heterozygous embryos varied over time, suggesting that non-random fertilization was dependent on an external factor that changed over time. As a higher frequency of heterozygous individuals correlated with an uncontrolled epidemic by MHV (mouse hepatitis virus), we suggested that MHV-infection might have influenced the outcome of fertilization. Here, we present an experiment that tests this hypothesis. We infected randomly chosen mice with MHV and sham-infected control mice five days before pairing. We recovered the two-cell embryos from the oviduct, cultured them until the blastocyst stage, and determined the genotype of each resulting blastocyst by polymerase chain reaction. We found the pattern that we expected from our previous experiments: virus-infected mice produced more MHC-heterozygous embryos than sham-infected ones. This suggests that parents are able to promote specific combinations of MHC-haplotypes during fertilization according to the presence or absence of a viral infection.",,"['Rülicke, T', 'Chapuisat, M', 'Homberger, F R', 'Macas, E', 'Wedekind, C']",,,,
,PMC,Dissecting RNA recombination in vitro: role of RNA sequences and the viral replicase.,http://dx.doi.org/10.1093/emboj/17.8.2392,PMC1170582,,,"Molecular mechanisms of RNA recombination were studied in turnip crinkle carmovirus (TCV), which has a uniquely high recombination frequency and non-random crossover site distribution among the recombining TCV-associated satellite RNAs. To test the previously proposed replicase-driven template-switching mechanism for recombination, a partially purified TCV replicase preparation (RdRp) was programed with RNAs resembling the putative in vivo recombination intermediates. Analysis of the in vitro RdRp products revealed efficient generation of 3'-terminal extension products. Initiation of 3'-terminal extension occurred at or close to the base of a hairpin that was a recombination hotspot in vivo. Efficient generation of the 3'-terminal extension products depended on two factors: (i) a hairpin structure in the acceptor RNA region and (ii) a short base-paired region formed between the acceptor RNA and the nascent RNA synthesized from the donor RNA template. The hairpin structure bound to the RdRp, and thus is probably involved in its recruitment. The probable role of the base-paired region is to hold the 3' terminus near the RdRp bound to the hairpin structure to facilitate 3'-terminal extension. These regions were also required for in vivo RNA recombination between TCV-associated sat-RNA C and sat-RNA D, giving crucial and direct support for a replicase-driven template-switching mechanism of RNA recombination.",,"['Nagy, P D', 'Zhang, C', 'Simon, A E']",,,,
,PMC,"Natural Pathogens of Laboratory Mice, Rats, and  Rabbits and Their Effects on Research",,PMC106832,,,"Laboratory mice, rats, and rabbits may harbor a variety of viral, bacterial, parasitic, and fungal agents. Frequently, these organisms cause no overt signs of disease. However, many of the natural pathogens of these laboratory animals may alter host physiology, rendering the host unsuitable for many experimental uses. While the number and prevalence of these pathogens have declined considerably, many still turn up in laboratory animals and represent unwanted variables in research. Investigators using mice, rats, and rabbits in biomedical experimentation should be aware of the profound effects that many of these agents can have on research.",,"Baker, David G.",,,,
,PMC,Investigation of the role of delayed-type-hypersensitivity responses to myelin in the pathogenesis of Theiler's virus-induced demyelinating disease.,,PMC1364124,,,"The contribution of autoimmune responses to the pathogenesis of Theiler's virus-induced demyelinating disease was investigated. Delayed-type hypersensitivity responses to myelin were examined in both symptomatic and asymptomatic mice at different times post-infection, in order to determine whether autoreactivity correlates with the development of demyelination. The results indicate that although autoimmune responses probably do not play a major role in the initiation of demyelination at early times post-infection, autoreactivity to myelin antigens dose eventually develop in symptomatic animals, perhaps through the mechanism of epitope spreading. Autoimmunity to myelin components is therefore an additional factor that may contribute to lesion progression in chronically diseased animals.",,"['Borrow, P', 'Welsh, C J', 'Tonks, P', 'Dean, D', 'Blakemore, W F', 'Nash, A A']",,,,
,PMC,Identification of a Novel Enteric Helicobacter Species in a Kitten with Severe Diarrhea,,PMC104659,,,"A previously undescribed Helicobacter sp. was recovered from a cat with severe diarrhea. Based upon the absence of any other identifiable cause of diarrhea, this helicobacter may be involved in the development of the disease signs. The organism could not be cultured but was described on the basis of 16S rRNA gene sequence analysis and morphology and appeared to be a new species, with Helicobacter canis being the most genetically similar species. The presence of a diarrhea-inducing helicobacter in a companion animal may pose a risk of zoonosis.",,"['Foley, Janet E.', 'Solnick, Jay V.', 'Lapointe, Jean-Martin', 'Jang, Spencer', 'Pedersen, Niels C.']",,,,
,PMC,Acceleration in the Rate of CNS Remyelination in Lysolecithin-Induced Demyelination,http://dx.doi.org/10.1523/JNEUROSCI.18-07-02498.1998,PMC6793082,,,"One important therapeutic goal during CNS injury from trauma or demyelinating diseases such as multiple sclerosis is to develop methods to promote remyelination. We tested the hypothesis that spontaneous remyelination in the toxic nonimmune model of lysolecithin-induced demyelination can be enhanced by manipulating the inflammatory response. In PBS-treated SJL/J mice, the number of remyelinating axons per square millimeter of lesion area increased significantly 3 and 5 weeks after lysolecithin injection in the spinal cord. However, methylprednisolone or a monoclonal antibody (mAb), SCH94.03, developed for its ability to promote remyelination in the Theiler’s virus murine model of demyelination, further increased the number of remyelinating axons per lesion area at 3 weeks by a factor of 2.6 and 1.9, respectively, but did not increase the ratio of myelin sheath thickness to axon diameter or the number of cells incorporating tritiated thymidine in the lesion. After 3 weeks, the number of remyelinating axons in the methylprednisolone or mAb SCH94.03 treatment groups was similar to the spontaneous remyelination in the 5 week PBS control-treated group, indicating that these treatments promoted remyelination by increasing its rate rather than its extent. To address a mechanism for promoting remyelination, through an effect on scavenger function, we assessed morphometrically the number of macrophages in lesions after methylprednisolone and mAb SCH94.03 treatment. Methylprednisolone reduced the number of macrophages, but SCH94.03 did not, although both enhanced remyelination. This study supports the hypothesis that even in toxic nonprimary immune demyelination, manipulating the inflammatory response is a benefit in myelin repair.",,"['Pavelko, Kevin D.', 'van Engelen, Baziel G. M.', 'Rodriguez, Moses']",,,,
,PMC,Monitoring and management of acidosis in calf diarrhoea.,,PMC1296639,,,,,"Grove-White, D H",,,,
,PMC,Intracellular Complexes of Viral Spike and Cellular Receptor Accumulate during Cytopathic Murine Coronavirus Infections,,PMC109802,,,"Murine hepatitis virus (MHV) infections exhibit remarkable variability in cytopathology, ranging from acutely cytolytic to essentially asymptomatic levels. In this report, we assess the role of the MHV receptor (MHVR) in controlling this variable virus-induced cytopathology. We developed human (HeLa) cell lines in which the MHVR was produced in a regulated fashion by placing MHVR cDNA under the control of an inducible promoter. Depending on the extent of induction, MHVR levels ranged from less than ∼1,500 molecules per cell (designated R(lo)) to ∼300,000 molecules per cell (designated R(hi)). Throughout this range, the otherwise MHV-resistant HeLa cells were rendered susceptible to infection. However, infection in the R(lo) cells occurred without any overt evidence of cytopathology, while the corresponding R(hi) cells died within 14 h after infection. When the HeLa-MHVR cells were infected with vaccinia virus recombinants encoding MHV spike (S) proteins, the R(hi) cells succumbed within 12 h postinfection; R(lo) cells infected in parallel were intact, as judged by trypan blue exclusion. This acute cytopathology was not due solely to syncytium formation between the cells producing S and MHVR, because fusion-blocking antiviral antibodies did not prevent it. These findings raised the possibility of an intracellular interaction between S and MHVR in the acute cell death. Indeed, we identified intracellular complexes of S and MHVR via coimmunoprecipitation of endoglycosidase H-sensitive forms of the two proteins. We suggest that MHV infections can become acutely cytopathic once these intracellular complexes rise above a critical threshold level.",,"['Rao, Pasupuleti V.', 'Gallagher, Thomas M.']",,,,
,PMC,Viruses and Cells with Mutations Affecting Viral Entry  Are Selected during Persistent Rotavirus  Infections of MA104 Cells,,PMC109759,,,"To better understand mechanisms of persistent rotavirus infections of cultured cells, we established independent, persistently infected cultures of MA104 cells, using rotavirus strain SA11. The cultures were either passaged when the cells reached confluence or supplemented with fresh medium every 7 days. Viral titers in culture lysates varied from 10(4) to 10(7) PFU per ml during 350 days of culture maintenance. Trypan blue staining indicated that 72 to 100% of cells in the cultures were viable, and immunocytochemical staining using a monoclonal antibody directed against viral protein VP6 demonstrated that 38 to 63% of the cells contained rotavirus antigen. We tested the capacity of rotaviruses isolated from the persistently infected cultures (PI viruses) to infect cells cured of persistent infection. Although wild-type (wt) and PI viruses produced equivalent yields in parental MA104 cells, PI viruses produced greater yields than wt virus in cured cells, which indicates that viruses and cells coevolve during persistent rotavirus infections of MA104 cells. To determine whether mutations in viruses and cells selected during these persistent infections affect viral entry, we tested the effect of trypsin treatment of the viral inoculum on growth of wt and PI viruses. Trypsin pretreatment is required for postattachment penetration of rotavirus virions into cells. In contrast to the case with wt virus, PI viruses produced equivalent yields with and without trypsin pretreatment in parental MA104 cells. However, PI viruses required trypsin pretreatment for efficient growth in cured cells. These results indicate that mutant viruses and cells are selected during maintenance of persistent rotavirus infections of MA104 cells and suggest that mutations in each affect trypsin-dependent steps in rotavirus entry.",,"['Mrukowicz, Jacek Z.', 'Wetzel, J. Denise', 'Goral, Mehmet I.', 'Fogo, Agnes B.', 'Wright, Peter F.', 'Dermody, Terence S.']",,,,
,PMC,A Single Amino Acid Change in the Hemagglutinin Protein of Measles Virus Determines Its Ability To Bind CD46 and Reveals Another Receptor on Marmoset B Cells,,PMC109736,,,"This paper provides evidence for a measles virus receptor other than CD46 on transformed marmoset and human B cells. We first showed that most tissues of marmosets are missing the SCR1 domain of CD46, which is essential for the binding of Edmonston measles virus, a laboratory strain that has been propagated in Vero monkey kidney cells. In spite of this deletion, the common marmoset was shown to be susceptible to infections by wild-type isolates of measles virus, although they did not support Edmonston measles virus production. As one would expect from these results, measles virus could not be propagated in owl monkey or marmoset kidney cell lines, but surprisingly, both a wild-type isolate (Montefiore 89) and the Edmonston laboratory strain of measles virus grew efficiently in B95-8 marmoset B cells. In addition, antibodies directed against CD46 had no effect on wild-type infections of marmoset B cells and only partially inhibited the replication of the Edmonston laboratory strain in the same cells. A direct binding assay with insect cells expressing the hemagglutinin (H) proteins of either the Edmonston or Montefiore 89 measles virus strains was used to probe the receptors on these B cells. Insect cells expressing Edmonston H but not the wild-type H bound to rodent cells with CD46 on their surface. On the other hand, both the Montefiore 89 H and Edmonston H proteins adhered to marmoset and human B cells. Most wild-type H proteins have asparagine residues at position 481 and can be converted to a CD46-binding phenotype by replacement of the residue with tyrosine. Similarly, the Edmonston H protein did not bind CD46 when its Tyr481 was converted to asparagine. However, this mutation did not affect the ability of Edmonston H to bind marmoset and human B cells. The preceding results provide evidence, through the use of a direct binding assay, that a second receptor for measles virus is present on primate B cells.",,"['Hsu, Eric C.', 'Sarangi, Farida', 'Iorio, Caterina', 'Sidhu, Mohinderjit S.', 'Udem, Stephen A.', 'Dillehay, Dirck L.', 'Xu, Wenbo', 'Rota, Paul A.', 'Bellini, William J.', 'Richardson, Christopher D.']",,,,
,PMC,Inhibition of Hepatitis B Virus Replication during Adenovirus and Cytomegalovirus Infections in Transgenic Mice,,PMC109701,,,"We have previously demonstrated that hepatitis B virus (HBV) replication and gene expression are abolished in the livers of HBV transgenic mice by cytotoxic T lymphocytes (CTLs) and during lymphocytic choriomeningitis virus (LCMV) infection, stimuli that trigger the production of alpha/beta interferon, gamma interferon, and tumor necrosis factor alpha in the liver. We now report that hepatic HBV replication and gene expression are inhibited by the local induction of these cytokines during adenovirus- and murine cytomegalovirus (MCMV)-induced hepatitis. Further, we show that MCMV also blocks HBV replication and gene expression in the proximal convoluted tubules of the kidney by causing interstitial nephritis and inducing the same cytokines in the renal parenchyma. These results suggest that inflammatory cytokines probably contribute to viral clearance during acute viral hepatitis in humans, and they imply that induction of these cytokines in the liver and other infected tissues of chronically infected patients might have therapeutic value.",,"['Cavanaugh, Victoria J.', 'Guidotti, Luca G.', 'Chisari, Francis V.']",,,,
,PMC,"Pathogenesis of lower respiratory tract infections due to Chlamydia, Mycoplasma, Legionella and viruses",,PMC1745181,,,,,"Andersen, P.",,,,
,PMC,Quantitative systematic review of randomised controlled trials comparing antibiotic with placebo for acute cough in adults,,PMC28496,,,"Objectives: To assess whether antibiotic treatment for acute cough is effective and to measure the side effects of such treatment. Design: Quantitative systematic review of randomised placebo controlled trials. Data sources: Nine trials (8 published, 1 unpublished) retrieved from a systematic search (electronic databases, contact with authors, contact with drug manufacturers, reference lists); no restriction on language. Main outcome measures: Proportion of subjects with productive cough at follow up (7-11 days after consultation with general practitioner); proportion of subjects who had not improved clinically at follow up; proportion of subjects who reported side effects from taking antibiotic or placebo. Results: Eight trials contributed to the meta-analysis. Resolution of cough was not affected by antibiotic treatment (relative risk 0.85 (95% confidence interval 0.73 to 1.00)), neither was clinical improvement at re-examination (relative risk 0.62 (0.36 to 1.09)). The side effects of antibiotic were more common in the antibiotic group when compared to placebo (relative risk 1.51 (0.86 to 2.64)). Conclusions: Treatment with antibiotic does not affect the resolution of cough or alter the course of illness. The benefits of antibiotic treatment are marginal for most patients with acute cough and may be outweighed by the side effects of treatment.",,"['Fahey, Tom', 'Stocks, Nigel', 'Thomas, Toby']",,,,
,PMC,Brome mosaic virus RNA replication protein 1a dramatically  increases in vivo stability but not translation  of viral genomic RNA3,,PMC19301,,,"Brome mosaic virus (BMV), a positive-strand RNA virus in the alphavirus-like superfamily, encodes two RNA replication proteins: 1a, which contains a helicase-like domain and a domain implicated in RNA capping, and 2a, which contains a polymerase-like domain. To further explore their functions, we expressed 1a and 2a individually and together in yeast also expressing replicatable transcripts of BMV genomic RNA3. Complementing prior results that 1a and 2a are required jointly for positive-strand RNA synthesis, both also were required for negative-strand RNA synthesis. Nevertheless, in the absence of 2a, 1a expression increased the accumulation of DNA-derived RNA3 transcripts 8-fold. Increased accumulation was specific for RNA3: none of a diverse set of yeast mRNAs tested showed increased accumulation in the presence of 1a. Increased RNA3 accumulation was not due to increased DNA transcription, but to a 20- to 40-fold increase in the in vivo half-life of RNA3 from 5–10 min in the absence of 1a to more than 3 hr in the presence of 1a. Although (1a+2a)-dependent RNA replication selectively amplified the natural viral 5′ end from among multiple transcription starts of DNA-derived RNA3 transcripts, 1a-induced stabilization affected all RNA3 transcripts, without specificity for the precise viral 5′ end. Increased RNA3 accumulation did not increase expression of a directly translatable, 5′-proximal gene in RNA3, implying that 1a-induced stabilization blocked rather than facilitated RNA3 translation. These and other results suggest that the striking, 1a-induced stabilization of RNA3 may reflect an interaction involved in recruiting viral RNA templates into RNA replication while diverting them from the competing processes of translation and degradation.",,"['Janda, Michael', 'Ahlquist, Paul']",,,,
,PMC,Immunodepression Induced by Trypanosoma cruzi and Mouse Hepatitis Virus Type 3 Is Associated with Thymus Apoptosis,,PMC121356,,,"Trypanosoma cruzi-infected mice show disturbance in the peripheral immune system such as polyclonal lymphocyte activation, autoantibody production, and immunosuppression of T lymphocytes. Previous observations in our laboratory showed that some stocks of T. cruzi can be contaminated with mouse hepatitis virus type 3 (MHV-3). Literature has shown that MHV-3 infection induces immunologic disorders characterized by thymic involution with marked cell depletion. However, the effects of interactions between MHV-3 and the parasite on the immune system are not well understood. In the present study specific-pathogen-free CBA mice were inoculated with MHV-3, alone or associated with different stocks of T. cruzi. Concurrent murine virus infection resulted in increased pathogenicity of T. cruzi infection shown by profound thymic atrophy; loss of cortical thymocytes; depletion of Thy1.2(+), CD4(+), and CD8(+) cells; enhancement of in situ labeling of nuclear DNA fragmentation; and eventually, death of the animals. Such lines of evidence show that the mechanism underlying this thymic atrophy is associated with apoptosis. These results also suggest that MHV-3 can account for the increased immunosuppression observed during experimental infection with the parasite.",,"['Verinaud, Liana', 'Da Cruz-Höfling, Maria Alice', 'Sakurada, Júlia K.', 'Rangel, Humberto A.', 'Vassallo, José', 'Wakelin, Derek', 'Sewell, Herb F.', 'Camargo, Irineu J. B.']",,,,
,PMC,Increased immunoglobulin G production by short term cultured duodenal biopsy samples from HIV infected patients,,PMC1727036,,,"Background—Secretory immunity is a major defence mechanism against infections at mucosal surfaces which are common in HIV infected patients. 
Aims—To analyse intestinal immunoglobulin production in HIV infection in comparison with that in saliva and serum. 
Patients and methods—Immunoglobulin G (IgG), A (IgA), and M (IgM) concentrations were determined in supernatants of short term cultured duodenal biopsy samples, serum, and saliva from HIV infected patients (n = 28) and controls (n = 14) by radial immunodiffusion. 
Results—IgG was increased in the supernatants of short term cultured biopsy samples and saliva from HIV infected patients compared with controls (p<0.01), but IgA and IgM levels were normal. In contrast, both IgG and IgA concentrations in serum were higher in HIV infected patients than in controls (p<0.002). No correlation was found between IgA produced by duodenal biopsy specimens and serum IgA. 
Conclusion—Abnormalities in mucosal immunoglobulin production in HIV infection were suprisingly small, indicating that specific secretory immunity rather than quantitative immunoglobulin production may be impaired. However, increased production of IgG could contribute to mucosal inflammation by complement activation. Our findings of normal mucosal IgA production and the lack of correlation between serum and mucosal IgA argues against an intestinal origin for the increased serum IgA levels in HIV infected patients. 

 Keywords: mucosal immunity; HIV infection; intestinal antibodies",,"['Schneider, T', 'Zippel, T', 'Schmidt, W', 'Pauli, G', 'Wahnschaffe, U', 'Chakravarti, S', 'Heise, W', 'Riecken, E', 'Zeitz, M', 'Ullrich, R']",,,,
,PMC,Reduction of Carriage of Enterohemorrhagic Escherichia coli  O157:H7 in Cattle by Inoculation with Probiotic Bacteria,,PMC104601,,,"Bacteria inhibitory to Escherichia coli O157:H7 were isolated from cattle and evaluated for their potential for reducing carriage of E. coli O157:H7 in calves. Eighteen of 1,200 bacterial isolates from cattle feces and intestinal tissue samples were screened and determined to inhibit the growth of E. coli O157:H7 in vitro. Seventeen of the isolates were E. coli and one was Proteus mirabilis. None produced Shiga toxin. Genomic DNA fingerprinting by pulsed-field gel electrophoresis revealed 13 distinguishable profiles among the 18 isolates. Two calves inoculated perorally with a mixture of all 18 isolates (10(10) CFU) appeared to be normal and did not develop signs of clinical disease throughout a 25- to 27-day observation period. These bacteria colonized segments of the gastrointestinal tract and were in feces at the termination of the experiment (25 and 27 days postinoculation) at levels of 50 to 200 CFU/g. Fifteen cannulated calves were studied to determine the efficiency of the probiotic bacteria in reducing or eliminating the carriage of E. coli O157:H7. Nine calves served as controls, with each animal receiving perorally 10(10) CFU of E. coli O157:H7. E. coli O157:H7 was detected intermittently in the rumen samples from all control animals throughout 3 weeks postinoculation, whereas E. coli O157:H7 was shed at various levels in feces continuously throughout the experiment (mean, 28 days). E. coli O157:H7 was isolated from the rumens and colons of eight of nine and nine of nine calves, respectively, at the termination of the study. Six calves each received perorally 10(10) CFU of probiotic bacteria and then 2 days later received 10(10) CFU of E. coli O157:H7. E. coli O157:H7 was detected in the rumen for only 9 days postinoculation in two animals, for 16 days in one animal, for 17 days in two animals, and for 29 days in one animal. E. coli O157:H7 was detected in feces for only 11 days postinoculation in one animal, for 15 days in one animal, for 17 days in one animal, for 18 days in one animal, for 19 days in one animal, and for 29 days in one animal. At the end of the experiment (mean, 30 days), E. coli O157:H7 was not recovered from the rumen of any of the six animals treated with probiotic bacteria; however, E. coli O157:H7 was recovered from the feces of one of the animals. This animal was fasted twice postinoculation. These studies indicate that selected probiotic bacteria administered to cattle prior to exposure to E. coli O157:H7 can reduce the level of carriage of E. coli O157:H7 in most animals.",,"['Zhao, Tong', 'Doyle, Michael P.', 'Harmon, Barry G.', 'Brown, Cathy A.', 'Mueller, P. O. Eric', 'Parks, Andrew H.']",,,,
,PMC,Effect of Nitric Oxide on Poliovirus Infection of Two Human Cell Lines,,PMC109559,,,"The role of nitric oxide after poliovirus infection of the human HeLa (carcinoma) and U937 (promonocytic) cell lines has been analyzed. Both types of cells produced detectable levels of nitric oxide after poliovirus infection. However, this production was not sufficient to limit viral productivity. On the other hand, pretreatment with the nitric oxide donor glycerine trinitrate lengthened the course of poliovirus infection.",,"['López-Guerrero, José A.', 'Carrasco, Luis']",,,,
,PMC,Mouse Hepatitis Virus 3C-Like Protease Cleaves a 22-Kilodalton Protein from the Open Reading Frame 1a Polyprotein  in Virus-Infected Cells and In Vitro,,PMC109524,,,"The 3C-like proteinase (3CLpro) of mouse hepatitis virus (MHV) is predicted to cleave at least 11 sites in the 803-kDa gene 1 polyprotein, resulting in maturation of proteinase, polymerase, and helicase proteins. However, most of these cleavage sites have not been experimentally confirmed and the proteins have not been identified in vitro or in virus-infected cells. We used specific antibodies to identify and characterize a 22-kDa protein (p1a-22) expressed from gene 1 in MHV A59-infected DBT cells. Processing of p1a-22 from the polyprotein began immediately after translation, but some processing continued for several hours. Amino-terminal sequencing of p1a-22 purified from MHV-infected cells showed that it was cleaved at a putative 3CLpro cleavage site, Gln_Ser(4014) (where the underscore indicates the site of cleavage), that is located between the 3CLpro domain and the end of open reading frame (ORF) 1a. Subclones of this region of gene 1 were used to express polypeptides in vitro that contained one or more 3CLpro cleavage sites, and cleavage of these substrates by recombinant 3CLpro in vitro confirmed that amino-terminal cleavage of p1a-22 occurred at Gln_Ser(4014). We demonstrated that the carboxy-terminal cleavage of the p1a-22 protein occurred at Gln_Asn(4208), a sequence that had not been predicted as a site for cleavage by MHV 3CLpro. Our results demonstrate the usefulness of recombinant MHV 3CLpro in identifying and confirming cleavage sites within the gene 1 polyprotein. Based on our results, we predict that at least seven mature proteins are processed from the ORF 1a polyprotein by 3CLpro and suggest that additional noncanonical cleavage sites may be used by 3CLpro during processing of the gene 1 polyprotein.",,"['Lu, Xiao Tao', 'Sims, Amy C.', 'Denison, Mark R.']",,,,
,PMC,A Retention Signal Necessary and Sufficient for Endoplasmic Reticulum Localization Maps to the Transmembrane  Domain of Hepatitis C Virus Glycoprotein E2,,PMC109514,,,"The hepatitis C virus (HCV) genome encodes two envelope glycoproteins (E1 and E2). These glycoproteins interact to form a noncovalent heterodimeric complex which is retained in the endoplasmic reticulum (ER). To identify whether E1 and/or E2 contains an ER-targeting signal potentially involved in ER retention of the E1-E2 complex, these proteins were expressed alone and their intracellular localization was studied. Due to misfolding of E1 in the absence of E2, no conclusion on the localization of its native form could be drawn from the expression of E1 alone. E2 expressed in the absence of E1 was shown to be retained in the ER similarly to E1-E2 complex. Chimeric proteins in which E2 domains were exchanged with corresponding domains of a protein normally transported to the plasma membrane (CD4) were constructed to identify the sequence responsible for its ER retention. The transmembrane domain (TMD) of E2 (C-terminal 29 amino acids) was shown to be sufficient for retention of the ectodomain of CD4 in the ER compartment. Replacement of the E2 TMD by the anchor signal of CD4 or a glycosyl phosphatidylinositol (GPI) moiety led to its expression on the cell surface. In addition, replacement of the E2 TMD by the anchor signal of CD4 or a GPI moiety abolished the formation of E1-E2 complexes. Together, these results suggest that, besides having a role as a membrane anchor, the TMD of E2 is involved in both complex formation and intracellular localization.",,"['Cocquerel, Laurence', 'Meunier, Jean-Christophe', 'Pillez, André', 'Wychowski, Czeslaw', 'Dubuisson, Jean']",,,,
,PMC,Functional Characterization of Naturally Occurring Variants of Human Hepatitis B Virus Containing the Core Internal Deletion Mutation,,PMC109512,,,"Naturally occurring variants of human hepatitis B virus (HBV) containing the core internal deletion (CID) mutation have been found frequently in HBV carriers worldwide. Despite numerous sequence analysis reports of CID variants in patients, in the past decade, CID variants have not been characterized functionally, and thus their biological significance to HBV infection remains unclear. We report here two different CID variants identified from two patients that are replication defective, most likely due to the absence of detectable core protein. In addition, we were unable to detect the presence of the precore protein and e antigen from CID variants. However, the production of polymerase appeared to be normal. The replication defect of the CID variants can be rescued in trans by complementation with wild-type core protein. The rescued CID variant particles, which utilize the wild-type core protein, presumably are enveloped properly since they can be secreted into the medium and band at a position similar to that of mature wild-type Dane particles, as determined by gradient centrifugation analysis. Our results also provide an explanation for the association of CID variants with helper or wild-type HBV in nature. The significance of CID variants in HBV infection and pathogenesis is discussed.",,"['Yuan, Thomas Ta-Tung', 'Lin, Min-Hui', 'Qiu, Sui Min', 'Shih, Chiaho']",,,,
,PMC,"Mutational Analysis of the Virus and Monoclonal Antibody Binding Sites in MHVR, the Cellular Receptor of the Murine Coronavirus Mouse Hepatitis Virus Strain A59",,PMC109486,,,"The primary cellular receptor for mouse hepatitis virus (MHV), a murine coronavirus, is MHVR (also referred to as Bgp1(a) or C-CAM), a transmembrane glycoprotein with four immunoglobulin-like domains in the murine biliary glycoprotein (Bgp) subfamily of the carcinoembryonic antigen (CEA) family. Other murine glycoproteins in the Bgp subfamily, including Bgp1(b) and Bgp2, also can serve as MHV receptors when transfected into MHV-resistant cells. Previous studies have shown that the 108-amino-acid N-terminal domain of MHVR is essential for virus receptor activity and is the binding site for monoclonal antibody (MAb) CC1, an antireceptor MAb that blocks MHV infection in vivo and in vitro. To further elucidate the regions of MHVR required for virus receptor activity and MAb CC1 binding, we constructed chimeras between MHVR and other members of the CEA family and tested them for MHV strain A59 (MHV-A59) receptor activity and MAb CC1 binding activity. In addition, we used site-directed mutagenesis to introduce selected amino acid changes into the N-terminal domains of MHVR and these chimeras and tested the abilities of these mutant glycoproteins to bind MAb CC1 and to function as MHV receptors. Several recombinant glycoproteins exhibited virus receptor activity but did not bind MAb CC1, indicating that the virus and MAb binding sites on the N-terminal domain of MHVR are not identical. Analysis of the recombinant glycoproteins showed that a short region of MHVR, between amino acids 34 and 52, is critical for MHV-A59 receptor activity. Additional regions of the N-terminal variable domain and the constant domains, however, greatly affected receptor activity. Thus, the molecular context in which the amino acids critical for MHV-A59 receptor activity are found profoundly influences the virus receptor activity of the glycoprotein.",,"['Wessner, David R.', 'Shick, Paul C.', 'Lu, Jin-Hua', 'Cardellichio, Christine B.', 'Gagneten, Sara E.', 'Beauchemin, Nicole', 'Holmes, Kathryn V.', 'Dveksler, Gabriela S.']",,,,
,PMC,The Mof2/Sui1 Protein Is a General Monitor of Translational Accuracy,,PMC108865,,,"Although it is essential for protein synthesis to be highly accurate, a number of cases of directed ribosomal frameshifting have been reported in RNA viruses, as well as in procaryotic and eucaryotic genes. Changes in the efficiency of ribosomal frameshifting can have major effects on the ability of cells to propagate viruses which use this mechanism. Furthermore, studies of this process can illuminate the mechanisms involved in the maintenance of the normal translation reading frame. The yeast Saccharomyces cerevisiae killer virus system uses programmed −1 ribosomal frameshifting to synthesize its gene products. Strains harboring the mof2-1 allele demonstrated a fivefold increase in frameshifting and prevented killer virus propagation. In this report, we present the results of the cloning and characterization of the wild-type MOF2 gene. mof2-1 is a novel allele of SUI1, a gene previously shown to play a role in translation initiation start site selection. Strains harboring the mof2-1 allele demonstrated a mutant start site selection phenotype and increased efficiency of programmed −1 ribosomal frameshifting and conferred paromomycin sensitivity. The increased frameshifting observed in vivo was reproduced in extracts prepared from mof2-1 cells. Addition of purified wild-type Mof2p/Sui1p reduced frameshifting efficiencies to wild-type levels. Expression of the human SUI1 homolog in yeast corrects all of the mof2-1 phenotypes, demonstrating that the function of this protein is conserved throughout evolution. Taken together, these results suggest that Mof2p/Sui1p functions as a general modulator of accuracy at both the initiation and elongation phases of translation.",,"['Cui, Ying', 'Dinman, Jonathan D.', 'Kinzy, Terri Goss', 'Peltz, Stuart W.']",,,,
,PMC,Experimental evolution of complexity: in vitro emergence of intermolecular ribozyme interactions.,,PMC1369616,,,"In the course of evolving variants of the Tetrahymena thermophila Group I ribozyme for improved DNA cleavage in vitro, we witnessed the unexpected emergence of a derived molecular species, capable of acting as a partner for the ribozyme, but no longer autocatalytic. This new RNA species exhibits a deletion in the catalytic core and participates in a productive intermolecular interaction with an active ribozyme, thus insuring its survival in the population. These novel RNA molecules have evolved a precise catalytic interaction with the Group I ribozyme and depend for their survival on the continued presence of active catalysts. This interaction hints at the complexity that may inevitably arise even in simple evolving systems.",,"['Hanczyc, M M', 'Dorit, R L']",,,,
,PMC,Comparative genetics of resistance to viruses.,,PMC1376908,,,,,"Brownstein, D G",,,,
,PMC,Increased tumor necrosis factor-alpha (TNF-alpha) gene expression in parainfluenza type 1 (Sendai) virus-induced bronchiolar fibrosis.,,PMC1857970,,,"Increased airway resistance and airway hyperresponsiveness induced in rats by infection with parainfluenza type I (Sendai) virus is associated with bronchiolar fibrosis. To determine whether increased tumor necrosis factor (TNF)-alpha gene expression is an important regulatory event in virus-induced bronchiolar fibrosis, pulmonary TNF-alpha mRNA and protein expression was assessed in rat strains that are susceptible (Brown Norway; BN) and resistant (Fischer 344; F344) to virus-induced bronchiolar fibrosis. Virus-inoculated BN rats had increased TNF-alpha pulmonary mRNA levels (P < 0.05) and increased numbers of bronchiolar macrophages and fibroblasts expressing TNF-alpha protein compared with virus-inoculated F344 rats (P < 0.05). Virus inoculation also induced elevated TNF-alpha mRNA and protein levels (P < 0.05) in cultured rat alveolar macrophages (NR8383 cells). A 55-kd soluble TNF receptor-immunoglobulin G fusion protein (sTNFR-IgG) was used to inhibit TNF-alpha bioactivity in virus-inoculated BN rats. Treated rats had fewer proliferating bronchiolar fibroblasts, as detected by bromodeoxyuridine incorporation, compared with virus-inoculated control rats (P < 0.05). There was also increased mortality in p55sTNFR-IgG-treated virus-inoculated rats associated with increased viral replication and decreased numbers of macrophages and lymphocytes in bronchoalveolar lavage fluid (P < 0.05). The results of this study indicate that 1) Sendai virus can directly up-regulate TNF-alpha mRNA and protein expression in macrophages, 2) TNF-alpha is an important mediator of virus-induced bronchiolar fibrosis, and 3) TNF-alpha has a critical role in the termination of Sendai viral replication in the lung.",,"['Uhl, E. W.', 'Moldawer, L. L.', 'Busse, W. W.', 'Jack, T. J.', 'Castleman, W. L.']",,,,
,PMC,Viruses and Bacteria in the Etiology of the Common Cold,,PMC104573,,,"Two hundred young adults with common colds were studied during a 10-month period. Virus culture, antigen detection, PCR, and serology with paired samples were used to identify the infection. Viral etiology was established for 138 of the 200 patients (69%). Rhinoviruses were detected in 105 patients, coronavirus OC43 or 229E infection was detected in 17, influenza A or B virus was detected in 12, and single infections with parainfluenza virus, respiratory syncytial virus, adenovirus, and enterovirus were found in 14 patients. Evidence for bacterial infection was found in seven patients. Four patients had a rise in antibodies against Chlamydia pneumoniae, one had a rise in antibodies against Haemophilus influenzae, one had a rise in antibodies against Streptococcus pneumoniae, and one had immunoglobulin M antibodies against Mycoplasma pneumoniae. The results show that although approximately 50% of episodes of the common cold were caused by rhinoviruses, the etiology can vary depending on the epidemiological situation with regard to circulating viruses. Bacterial infections were rare, supporting the concept that the common cold is almost exclusively a viral disease.",,"['Mäkelä, Mika J.', 'Puhakka, Tuomo', 'Ruuskanen, Olli', 'Leinonen, Maija', 'Saikku, Pekka', 'Kimpimäki, Marko', 'Blomqvist, Soile', 'Hyypiä, Timo', 'Arstila, Pertti']",,,,
,PMC,The Spike Protein of Murine Coronavirus Mouse Hepatitis Virus Strain A59 Is Not Cleaved in Primary Glial Cells and Primary Hepatocytes,,PMC124642,,,"Mouse hepatitis virus strain A59 (MHV-A59) produces meningoencephalitis and severe hepatitis during acute infection. Infection of primary cells derived from the central nervous system (CNS) and liver was examined to analyze the interaction of virus with individual cell types derived from the two principal sites of viral replication in vivo. In glial cell cultures derived from C57BL/6 mice, MHV-A59 produces a productive but nonlytic infection, with no evidence of cell-to-cell fusion. In contrast, in continuously cultured cells, this virus produces a lytic infection with extensive formation of syncytia. The observation of few and delayed syncytia following MHV-A59 infection of hepatocytes more closely resembles infection of glial cells than that of continuously cultured cell lines. For MHV-A59, lack of syncytium formation correlates with lack of cleavage of the fusion glycoprotein, or spike (S) protein. The absence of cell-to-cell fusion following infection of both primary cell types prompted us to examine the cleavage of the spike protein. Cleavage of S protein was below the level of detection by Western blot analysis in MHV-A59-infected hepatocytes and glial cells. Furthermore, no cleavage of this protein was detected in liver homogenates from C57BL/6 mice infected with MHV-A59. Thus, cleavage of the spike protein does not seem to be essential for entry and spread of the virus in vivo, as well as for replication in vitro.",,"['Hingley, Susan T.', 'Leparc-Goffart, Isabelle', 'Weiss, Susan R.']",,,,
,PMC,Neuronal Cell Surface Molecules Mediate Specific Binding to Rabies Virus Glycoprotein Expressed by a Recombinant Baculovirus on the Surfaces of Lepidopteran Cells,,PMC124581,,,"The existence of specific rabies virus (RV) glycoprotein (G) binding sites on the surfaces of neuroblastoma cells is demonstrated. Spodoptera frugiperda (Sf21) cells expressing G of the RV strain CVS (Gcvs-Sf21 cells) bind specifically to neuroblastoma cells of different species but not to any other cell type (fibroblast, myoblast, epithelial, or glioma). Attachment to mouse neuroblastoma NG108-15 cells is abolished by previous treatment of Gcvs-Sf21 cells with anti-G antibody. Substitutions for lysine at position 330 and for arginine at position 333 in RV G greatly reduce interaction between Gcvs-Sf21 cells and NG108-15 cells. These data are consistent with in vivo results: an avirulent RV mutant bearing the same double mutation is not able to infect sensory neurons or motoneurons (P. Coulon, J.-P. Ternaux, A. Flamand, and C. Tuffereau, J. Virol. 72:273–278, 1998) after intramuscular inoculation into a mouse. Furthermore, infection of NG108-15 cells by RV but not by vesicular stomatitis virus leads to a reduction of the number of binding sites at the neuronal-cell surface. Our data strongly suggest that these specific attachment sites on neuroblastoma cells represent a neuronal receptor(s) used by RV to infect certain types of neurons in vivo.",,"['Tuffereau, Christine', 'Benejean, Jacqueline', 'Alfonso, Anne-Marie Roque', 'Flamand, Anne', 'Fishman, Mark C.']",,,,
,PMC,The Pokeweed Antiviral Protein Specifically Inhibits  Ty1-Directed +1 Ribosomal Frameshifting and  Retrotransposition in Saccharomyces cerevisiae,,PMC124575,,,"Programmed ribosomal frameshifting is a molecular mechanism that is used by many RNA viruses to produce Gag-Pol fusion proteins. The efficiency of these frameshift events determines the ratio of viral Gag to Gag-Pol proteins available for viral particle morphogenesis, and changes in ribosomal frameshift efficiencies can severely inhibit virus propagation. Since ribosomal frameshifting occurs during the elongation phase of protein translation, it is reasonable to hypothesize that agents that affect the different steps in this process may also have an impact on programmed ribosomal frameshifting. We examined the molecular mechanisms governing programmed ribosomal frameshifting by using two viruses of the yeast Saccharomyces cerevisiae. Here, we present evidence that pokeweed antiviral protein (PAP), a single-chain ribosomal inhibitory protein that depurinates an adenine residue in the α-sarcin loop of 25S rRNA and inhibits translocation, specifically inhibits Ty1-directed +1 ribosomal frameshifting in intact yeast cells and in an in vitro assay system. Using an in vivo assay for Ty1 retrotransposition, we show that PAP specifically inhibits Ty1 retrotransposition, suggesting that Ty1 viral particle morphogenesis is inhibited in infected cells. PAP does not affect programmed −1 ribosomal frameshift efficiencies, nor does it have a noticeable impact on the ability of cells to maintain the M(1)-dependent killer virus phenotype, suggesting that −1 ribosomal frameshifting does not occur after the peptidyltransferase reaction. These results provide the first evidence that PAP has viral RNA-specific effects in vivo which may be responsible for the mechanism of its antiviral activity.",,"['Tumer, Nilgun E.', 'Parikh, Bijal A.', 'Li, Ping', 'Dinman, Jonathan D.']",,,,
,PMC,Proteolytic Processing at the Amino Terminus of Human Coronavirus 229E Gene 1-Encoded Polyproteins: Identification of  a Papain-Like Proteinase and Its Substrate,,PMC124560,,,"Expression of the coronavirus gene 1-encoded polyproteins, pp1a and pp1ab, is linked to a series of proteolytic events involving virus-encoded proteinases. In this study, we used transfection and immunoprecipitation assays to show that the human coronavirus 229E-encoded papain-like cysteine proteinase, PCP1, is responsible for the release of an amino-terminal protein, p9, from the gene 1-encoded polyproteins. The same protein, p9, has also been identified in virus-infected cells. Furthermore, using an in vitro trans-cleavage assay, we defined the proteolytic cleavage site at the carboxyl terminus of p9 as pp1a-pp1ab amino acids Gly-111 and Asn-112. These results and a comparative sequence analysis suggest that substrate positions P1 and P5 seem to be the major determinants of the PCP1 cleavage site and that the latter can occupy a variable position at the amino terminus of the coronavirus pp1a and pp1ab polyproteins. By combining the trans-cleavage assay with deletion mutagenesis, we were also able to locate the boundaries of the active PCP1 domain between pp1a-pp1ab amino acids Gly-861–Glu-975 and Asn-1209–Gln-1285. Finally, codon mutagenesis was used to show that Cys-1054 and His-1205 are essential for PCP1 proteolytic activity, suggesting that these amino acids most likely have a catalytic function.",,"['Herold, Jens', 'Gorbalenya, Alexander E.', 'Thiel, Volker', 'Schelle, Barbara', 'Siddell, Stuart G.']",,,,
,PMC,Invading the Yeast Nucleus: a Nuclear Localization Signal at the C Terminus of Ty1 Integrase Is Required  for Transposition In Vivo,,PMC108824,,,"Retrotransposon Ty1 faces a formidable cell barrier during transposition—the yeast nuclear membrane which remains intact throughout the cell cycle. We investigated the mechanism by which transposition intermediates are transported from the cytoplasm (the presumed site of Ty1 DNA synthesis) to the nucleus, where they are integrated into the genome. Ty1 integrase has a nuclear localization signal (NLS) at its C terminus. Both full-length integrase and a C-terminal fragment localize to the nucleus. C-terminal deletion mutants in Ty1 integrase were used to map the putative NLS to the last 74 amino acid residues of integrase. Mutations in basic segments within this region decreased retrotransposition at least 50-fold in vivo. Furthermore, these mutant integrase proteins failed to localize to the nucleus. Production of virus-like particles, reverse transcriptase activity, and complete in vitro Ty1 integration resembled wild-type levels, consistent with failure of the mutant integrases to enter the nucleus.",,"['Kenna, Margaret A.', 'Brachmann, Carrie Baker', 'Devine, Scott E.', 'Boeke, Jef D.']",,,,
,PMC,Characterization of the interaction between VP8 of bovine rotavirus C486 and cellular components on MA-104 cells and erythrocytes.,,PMC1189443,,,"Rotavirus VP8*, the N-terminal trypsin cleavage product of VP4, has been shown to bind to MA-104 cells and human O type erythrocytes. To examine whether bacterially expressed VP8* binds to cellular components of MA-104 cells, the VP8* (aa 1-247) was expressed in E. coli and radiolabelled with 35S-methionine. The radiolabelled rVP8* was immunoprecipitated with antiserum to bovine rotavirus C486 (BRV). The rVP8* was found to bind to MA-104 cells and its binding was competed by BRV. To study the interaction between VP8* and receptors of erythrocytes, hemagglutination (HA) and hemagglutination inhibition (HI) assays were carried out using solubilized rVP8*. rVP8* showed HA which could be inhibited by antiserum to BRV. This interaction was also inhibited by gangliosides, demonstrating a sialic acid dependent interaction. To study the contribution of the C-terminal region of VP8* to HA, a number of approaches were used. First, a peptide spanning aa 230-247 was synthesized and antisera was raised against the peptide to see whether it could inhibit HA of rVP8*. Second, a truncated form of VP8* (tVP8*: aa 1-229) was expressed to examine its hemagglutinating activity. Third, the dimerization of rVP8* and tVP8* was compared by Western-blotting following electrophoresis using native SDS-PAGE. The results indicated that antibody to aa 230-247 inhibits hemagglutination by preventing dimerization of VP8* which in turn allows the molecule to cause HA. To characterize the interaction between the HA domain and sialic acid receptors, erythrocytes were treated with sialidases of different specificities. Arthrobacter ureafaciens, Clostridium perfringens and alpha 2-8 linkage-specific neuraminidase destroyed the ability of sialic acid of erythrocytes to interact with rVP8*, indicating that bovine rotavirus C486 binding requires an alpha 2-8 linkage but acetylation of the sialic acid is not necessary.",,"['Lee, J', 'Yoo, D', 'Redmond, M J', 'Attah-Poku, S K', 'van den Hurk, J V', 'Babiuk, L A']",,,,
,PMC,Identification of the Leader-Body Junctions for the Viral Subgenomic mRNAs and Organization of the Simian Hemorrhagic Fever  Virus Genome: Evidence for Gene Duplication  during Arterivirus Evolution,,PMC109450,,,"Simian hemorrhagic fever virus (SHFV) was recently reclassified and assigned to the new virus family Arteriviridae. During replication, arteriviruses produce a 3′ coterminal, nested set of subgenomic mRNAs (sgRNAs). These sgRNAs arise by discontinuous transcription, and each contains a 5′ leader sequence which is joined to the body of the mRNA through a conserved junction sequence. Only the 5′-most open reading frame (ORF) is believed to be transcribed from each sgRNA. The SHFV genome encodes nine ORFs that are presumed to be expressed from sgRNAs. However, reverse transcription-PCR analysis with leader- and ORF-specific primers identified only eight sgRNA species. The consensus sequence 5′-UCNUUAACC-3′ was identified as the junction motif. Our data suggest that sgRNA 2 may be bicistronic, expressing both ORF 2a and ORF 2b. SHFV encodes three more ORFs on its genome than the other arteriviruses. Comparative sequence analysis suggested that SHFV ORFs 2a, 2b, and 3 are related to ORFs 2 through 4 of the other arteriviruses. Evidence which suggests that SHFV ORFs 4 through 6 are related to ORFs 2a through 3 and may have resulted from a recombination event during virus evolution is presented.",,"['Godeny, E. K.', 'de Vries, A. A. F.', 'Wang, X. C.', 'Smith, S. L.', 'de Groot, R. J.']",,,,
,PMC,The Coronavirus Transmissible Gastroenteritis Virus Causes Infection after Receptor-Mediated Endocytosis and Acid-Dependent Fusion with an Intracellular Compartment,,PMC109404,,,"Aminopeptidase N is a species-specific receptor for transmissible gastroenteritis virus (TGEV), which infects piglets, and for the 229E virus, which infects humans. It is not known whether these coronaviruses are endocytosed before fusion with a membrane of the target cell, causing a productive infection, or whether they fuse directly with the plasma membrane. We have studied the interaction between TGEV and a cell line (MDCK) stably expressing recombinant pig aminopeptidase N (pAPN). By electron microscopy and flow cytometry, TGEV was found to be associated with the plasma membrane after adsorption to the pAPN-MDCK cells. TGEV was also observed in endocytic pits and apical vesicles after 3 to 10 min of incubation at 38°C. The number of pits and apical vesicles was increased by the TGEV incubation, indicating an increase in endocytosis. After 10 min of incubation, a distinct TGEV-pAPN-containing population of large intracellular vesicles, morphologically compatible with endosomes, was found. A higher density of pAPN receptors was observed in the pits beneath the virus particles than in the surrounding plasma membrane, indicating that TGEV recruits pAPN receptors before endocytosis. Ammonium chloride and bafilomycin A(1) markedly inhibited the TGEV infection as judged from virus production and protein biosynthesis analyses but did so only when added early in the course of the infection, i.e., about 1 h after the start of endocytosis. Together our results point to an acid intracellular compartment as the site of fusion for TGEV.",,"['Hansen, G. H.', 'Delmas, B.', 'Besnardeau, L.', 'Vogel, L. K.', 'Laude, H.', 'Sjöström, H.', 'Norén, O.']",,,,
,PMC,The Viral Spike Protein Is Not Involved in the Polarized Sorting of Coronaviruses in Epithelial Cells,,PMC109400,,,"Coronaviruses are assembled by budding into a pre-Golgi compartment from which they are transported along the secretory pathway to leave the cell. In cultured epithelial cells, they are released in a polarized fashion; depending on the virus and cell type, they are sorted preferentially either to the apical domain or to the basolateral plasma membrane domain. In this study, we investigated the role of the coronavirus spike protein, because of its prominent position in the virion the prime sorting candidate, in the directionality of virus release. Three independent approaches were taken. (i) The inhibition of N glycosylation by tunicamycin resulted in the synthesis of spikeless virions. The absence of spikes, however, did not influence the polarity in the release of virions. Thus, murine hepatitis virus strain A59 (MHV-A59) was still secreted from the basolateral membranes of mTAL and LMR cells and from the apical sides of MDCK(MHVR) cells, whereas transmissible gastroenteritis virus (TGEV) was still released from the apical surfaces of LMR cells. (ii) Spikeless virions were also studied by using the MHV-A59 temperature-sensitive mutant Albany 18. When these virions were produced in infected LMR and MDCK(MHVR) cells at the nonpermissive temperature, they were again preferentially released from basolateral and apical membranes, respectively. (iii) We recently demonstrated that coronavirus-like particles resembling normal virions were assembled and released when the envelope proteins M and E were coexpressed in cells (H. Vennema, G.-J. Godeke, J. W. A. Rossen, W. F. Voorhout, M. C. Horzinek, D.-J. E. Opstelten, and P. J. M. Rottier, EMBO J. 15:2020–2028, 1996). The spikeless particles produced in mTAL cells by using recombinant Semliki Forest viruses to express these two genes of MHV-A59 were specifically released from basolateral membranes, i.e., with the same polarity as that of wild-type MHV-A59. Our results thus consistently demonstrate that the spike protein is not involved in the directional sorting of coronaviruses in epithelial cells. In addition, our observations with tunicamycin show that contrary to the results with some secretory proteins, the N-linked oligosaccharides present on the viral M proteins of coronaviruses such as TGEV also play no role in viral sorting. The implications of these conclusions are discussed.",,"['Rossen, J. W. A.', 'de Beer, R.', 'Godeke, G.-J.', 'Raamsman, M. J. B.', 'Horzinek, M. C.', 'Vennema, H.', 'Rottier, P. J. M.']",,,,
,PMC,Infectious Transcripts from Cloned Genome-Length cDNA of Porcine Reproductive and Respiratory Syndrome Virus,,PMC109385,,,"The 5′-terminal end of the genomic RNA of the Lelystad virus isolate (LV) of porcine reproductive and respiratory syndrome virus was determined. To construct full-length cDNA clones, the 5′-terminal sequence was ligated to cDNA clones covering the complete genome of LV. When RNA that was transcribed in vitro from these full-length cDNA clones was transfected into BHK-21 cells, infectious LV was produced and secreted. The virus was rescued by passage to porcine alveolar lung macrophages or CL2621 cells. When infectious transcripts were transfected to porcine alveolar lung macrophages or CL2621 cells, no infectious virus was produced due to the poor transfection efficiency of these cells. The growth properties of the viruses produced by BHK-21 cells transfected with infectious transcripts of LV cDNA resembled the growth properties of the parental virus from which the cDNA was derived. Two nucleotide changes leading to a unique PacI restriction site directly downstream of the ORF7 gene were introduced in the genome-length cDNA clone. The virus recovered from this mutated cDNA clone retained the PacI site, which confirmed the de novo generation of infectious LV from cloned cDNA. These results indicate that the infectious clone of LV enables us to mutagenize the viral genome at specific sites and that it will therefore be useful for detailed molecular characterization of the virus, as well as for the development of a safe and effective live vaccine for use in pigs.",,"['Meulenberg, J. J. M.', 'Bos-de Ruijter, J. N. A.', 'van de Graaf, R.', 'Wensvoort, G.', 'Moormann, R. J. M.']",,,,
,PMC,Antibody-Secreting Cell Responses and Protective Immunity Assessed in Gnotobiotic Pigs Inoculated Orally or Intramuscularly with Inactivated Human Rotavirus,,PMC109380,,,"Newborn gnotobiotic pigs were inoculated twice perorally (p.o.) (group 1) or intramuscularly (i.m.) (group 2) or three times i.m. (group 3) with inactivated Wa strain human rotavirus and challenged with virulent Wa human rotavirus 20 to 24 days later. To assess correlates of protection, antibody-secreting cells (ASC) were enumerated in intestinal and systemic lymphoid tissues from pigs in each group at selected postinoculation days (PID) or postchallenge days. Few virus-specific ASC were detected in any tissues of group 1 pigs prior to challenge. By comparison, groups 2 and 3 had significantly greater numbers of virus-specific immunoglobulin M (IgM) ASC in intestinal and splenic tissues at PID 8 and significantly greater numbers of virus-specific IgG ASC and IgG memory B cells in spleen and blood at challenge. However, as for group 1, few virus-specific IgA ASC or IgA memory B cells were detected in any tissues of group 2 and 3 pigs. Neither p.o. nor i.m. inoculation conferred significant protection against virulent Wa rotavirus challenge (0 to 6% protection rate), and all groups showed significant anamnestic virus-specific IgG and IgA ASC responses. Hence, high numbers of IgG ASC or memory IgG ASC in the systemic lymphoid tissues at the time of challenge did not correlate with protection. Further, our findings suggest that inactivated Wa human rotavirus administered either p.o. or parenterally is significantly less effective in inducing intestinal IgA ASC responses and conferring protective immunity than live Wa human rotavirus inoculated orally, as reported earlier (L. Yuan, L. A. Ward, B. I. Rosen, T. L. To, and L. J. Saif, J. Virol. 70:3075–3083, 1996). Thus, more efficient mucosal delivery systems and rotavirus vaccination strategies are needed to induce intestinal IgA ASC responses, identified previously as a correlate of protective immunity to rotavirus.",,"['Yuan, Lijuan', 'Kang, S.-Y.', 'Ward, Lucy A.', 'To, Thanh L.', 'Saif, Linda J.']",,,,
,PMC,Involvement of a subgenomic mRNA in the generation of a variable population of defective citrus tristeza virus molecules.,,PMC230293,,,"The fusion sites between the termini of naturally occurring defective RNAs (D-RNAs) from three citrus tristeza virus (CTV) isolates were sequenced. Seven of eight clones showed a common 3' terminus of 940 nucleotides (nt) fused to 5' termini with different sizes. An extra cytosine nucleotide was found at the junction site of the majority of the common 3' D-RNAs. Molecular analysis of the plus and minus strands of the 0.9-kbp double-stranded RNA, corresponding to the CTV open reading frame 11 subgenomic RNA (sgRNA), showed that they were identical in length and sequence to the common 3' sequence of the D-RNAs. These results imply that viral sgRNA messengers also function as building components for genomic rearrangement and exchange of complete viral genes.",,"['Yang, G', 'Mawassi, M', 'Gofman, R', 'Gafny, R', 'Bar-Joseph, M']",,,,
,PMC,Poliovirus-encoded 2C polypeptide specifically binds to the 3'-terminal sequences of viral negative-strand RNA.,,PMC230265,,,"The poliovirus-encoded, membrane-associated polypeptide 2C is believed to be required for initiation and elongation of RNA synthesis. We have expressed and purified recombinant, histidine-tagged 2C and examined its ability to bind to the first 100 nucleotides of the poliovirus 5' untranslated region of the positive strand and its complementary 3'-terminal negative-strand RNA sequences. Results presented here demonstrate that the 2C polypeptide specifically binds to the 3'-terminal sequences of poliovirus negative-strand RNA. Since this region is believed to form a stable cloverleaf structure, a number of mutations were constructed to examine which nucleotides and/or structures within the cloverleaf are essential for 2C binding. Binding of 2C to the 3'-terminal cloverleaf of the negative-strand RNA is greatly affected when the conserved sequence, UGUUUU, in stem a of the cloverleaf is altered. Mutational studies suggest that interaction of 2C with the 3'-terminal cloverleaf of negative-strand RNA is facilitated when the sequence UGUUUU is present in the context of a double-stranded structure. The implication of 2C binding to negative-strand RNA in viral replication is discussed.",,"['Banerjee, R', 'Echeverri, A', 'Dasgupta, A']",,,,
,PMC,The murine coronavirus mouse hepatitis virus strain A59 from persistently infected murine cells exhibits an extended host range.,,PMC230256,,,"In murine 17 Cl 1 cells persistently infected with murine coronavirus mouse hepatitis virus strain A59 (MHV-A59), expression of the virus receptor glycoprotein MHVR was markedly reduced (S. G. Sawicki, J. H. Lu, and K. V. Holmes, J. Virol. 69:5535-5543, 1995). Virus isolated from passage 600 of the persistently infected cells made smaller plaques on 17 Cl 1 cells than did MHV-A59. Unlike the parental MHV-A59, this variant virus also infected the BHK-21 (BHK) line of hamster cells. Virus plaque purified on BHK cells (MHV/BHK) grew more slowly in murine cells than did MHV-A59, and the rate of viral RNA synthesis was lower and the development of the viral nucleocapsid (N) protein was slower than those of MHV-A59. MHV/BHK was 100-fold more resistant to neutralization with the purified soluble recombinant MHV receptor glycoprotein (sMHVR) than was MHV-A59. Pretreatment of 17 Cl 1 cells with anti-MHVR monoclonal antibody CC1 protected the cells from infection with MHV-A59 but only partially protected them from infection with MHV/BHK. Thus, although MHV/BHK could still utilize MHVR as a receptor, its interactions with the receptor were significantly different from those of MHV-A59. To determine whether a hemagglutinin esterase (HE) glycoprotein that could bind the virions to 9-O-acetylated neuraminic acid moieties on the cell surface was expressed by MHV/BHK, an in situ esterase assay was used. No expression of HE activity was detected in 17 Cl 1 cells infected with MHV/BHK, suggesting that this virus, like MHV-A59, bound to cell membranes via its S glycoprotein. MHV/BHK was able to infect cell lines from many mammalian species, including murine (17 Cl 1), hamster (BHK), feline (Fcwf), bovine (MDBK), rat (RIE), monkey (Vero), and human (L132 and HeLa) cell lines. MHV/BHK could not infect dog kidney (MDCK I) or swine testis (ST) cell lines. Thus, in persistently infected murine cell lines that express very low levels of virus receptor MHVR and which also have and may express alternative virus receptors of lesser efficiency, there is a strong selective advantage for virus with altered interactions with receptor (D. S. Chen, M. Asanaka, F. S. Chen, J. E. Shively, and M. M. C. Lai, J. Virol. 71:1688-1691, 1997; D. S. Chen, M. Asanaka, K. Yokomori, F.-I. Wang, S. B. Hwang, H.-P. Li, and M. M. C. Lai, Proc. Natl. Acad. Sci. USA 92:12095-12099, 1995; P. Nedellec, G. S. Dveksler, E. Daniels, C. Turbide, B. Chow, A. A. Basile, K. V. Holmes, and N. Beauchemin, J. Virol. 68:4525-4537, 1994). Possibly, in coronavirus-infected animals, replication of the virus in tissues that express low levels of receptor might also select viruses with altered receptor recognition and extended host range.",,"['Schickli, J H', 'Zelus, B D', 'Wentworth, D E', 'Sawicki, S G', 'Holmes, K V']",,,,
,PMC,The function of the spike protein of mouse hepatitis virus strain A59 can be studied on virus-like particles: cleavage is not required for infectivity.,,PMC230247,,,"The spike protein (S) of the murine coronavirus mouse hepatitis virus strain A59 (MHV-A59) induces both virus-to-cell fusion during infection and syncytium formation. Thus far, only syncytium formation could be studied after transient expression of S. We have recently described a system in which viral infectivity is mimicked by using virus-like particles (VLPs) and reporter defective-interfering (DI) RNAs (E. C. W. Bos, W. Luytjes, H. Van der Meulen, H. K. Koerten, and W. J. M. Spaan, Virology 218:52-60, 1996). Production of VLPs of MHV-A59 was shown to be dependent on the expression of M and E. We now show in several ways that the infectivity of VLPs is dependent on S. Infectivity was lost when spikeless VLPs were produced. Infectivity was blocked upon treatment of the VLPs with MHV-A59-neutralizing anti-S monoclonal antibody (MAb) A2.3 but not with nonneutralizing anti-S MAb A1.4. When the target cells were incubated with antireceptor MAb CC1, which blocks MHV-A59 infection, VLPs did not infect the target cells. Thus, S-mediated VLP infectivity resembles MHV-A59 infectivity. The system can be used to identify domains in S that are essential for infectivity. As a first application, we investigated the requirements of cleavage of S for the infectivity of MHV-A59. We inserted three mutant S proteins that were previously shown to be uncleaved (E. C. W. Bos, L. Heijnen, W. Luytjes, and W. J. M. Spaan, Virology 214:453-463, 1995) into the VLPs. Here we show that cleavage of the spike protein of MHV-A59 is not required for infectivity.",,"['Bos, E C', 'Luytjes, W', 'Spaan, W J']",,,,
,PMC,Protein interactions during coronavirus assembly.,,PMC230230,,,"Coronaviruses assemble and obtain their envelope at membranes of the intermediate compartment between the endoplasmic reticulum and Golgi complex. Like other enveloped viruses, coronavirus assembly is presumably dependent on protein localization and protein-protein as well as protein-RNA interactions. We have used the bovine coronavirus (BCV) as a model to study interactions between the viral proteins in virus-infected cells that are important for coronavirus assembly. BCV is a prototype for the coronaviruses that express an additional major structural protein, the hemagglutinin esterase (HE), in addition to the spike (S) glycoprotein, membrane (M) glycoprotein, and nucleocapsid (N) protein. Complexes consisting of the M, S, and HE proteins were detected in virus-infected cells by coimmunoprecipitations. Kinetic analyses demonstrated that S protein and HE each quickly formed a complex with M protein after synthesis, whereas heterocomplexes consisting of all three proteins formed more slowly. The kinetics of HE biosynthesis revealed that the half-life of oligomerization was approximately 30 min, which correlated with the appearance of complexes consisting of M, HE, and S proteins, suggesting that oligomerization and/or conformational changes may be important for the S-M-HE protein complexes to form. Only HE dimers were found associated with the heterocomplexes consisting of all three proteins. S-M-HE protein complexes were detected prior to processing of the oligosaccharide chains on HE, indicating that these protein complexes formed in a premedial Golgi compartment before trimming of sugar chains. Transient coexpressions and double-labeling immunofluorescence demonstrated that HE and S proteins colocalized with M protein. This was further supported by coimmunoprecipitation of specific HE-M and S-M protein complexes from transfected cells, indicating that these proteins can form complexes in the absence of other viral proteins.",,"['Nguyen, V P', 'Hogue, B G']",,,,
,PMC,Fulminant hepatic failure in murine hepatitis virus strain 3 infection: tissue-specific expression of a novel fgl2 prothrombinase.,,PMC230225,,,"Activation of the immune coagulation system has been implicated in the pathogenesis of fulminant liver failure caused by murine hepatitis virus strain 3 (MHV-3). The recent discovery of the fgl2 gene, which encodes for MHV-3-induced prothrombinase (fgl2 prothrombinase), allows for fundamental studies to determine the molecular basis for fulminant liver failure. Transcription of the fgl2 gene and translation of the protein it encodes were examined in the liver and other organs of susceptible mice following MHV-3 infection. No constitutive expression of the fgl2 gene or the fgl2 prothrombinase was detected. Within 12 to 24 h of MHV-3 infection, however, fgl2 gene transcripts were detected in large amounts in the liver, spleen, and lungs, all of which are rich in reticuloendothelial cells, but were only focally present in small amounts in the kidney and brain. There was sequential detection of fgl2 prothrombinase in the liver, where it was localized specifically to the endothelium of intrahepatic veins and hepatic sinusoids; this was allowed by fibrin deposition, which resulted in confluent hepatocellular necrosis. These results provide further evidence for the role of the selective expression of this novel fgl2 prothrombinase in the pathogenesis of MHV-3-induced fulminant liver failure.",,"['Ding, J W', 'Ning, Q', 'Liu, M F', 'Lai, A', 'Leibowitz, J', 'Peltekian, K M', 'Cole, E H', 'Fung, L S', 'Holloway, C', 'Marsden, P A', 'Yeger, H', 'Phillips, M J', 'Levy, G A']",,,,
,PMC,Identification of spike protein residues of murine coronavirus responsible for receptor-binding activity by use of soluble receptor-resistant mutants.,,PMC230203,,,"We previously demonstrated by site-directed mutagenesis analysis that the amino acid residues at positions 62 and 214 to 216 in the N-terminal region of mouse hepatitis virus (MHV) spike (S) protein are important for receptor-binding activity (H. Suzuki and F. Taguchi, J. Virol. 70:2632-2636, 1996). To further identify the residues responsible for the activity, we isolated the mutant viruses that were not neutralized with the soluble form of MHV receptor proteins, since such mutants were expected to have mutations in amino acids responsible for receptor-binding activity. Five soluble-receptor-resistant (srr) mutants isolated had mutations in a single amino acid at three different positions: one was at position 65 (Leu to His) (srr11) in the S1 subunit and three were at position 1114 (Leu to Phe) (srr3, srr4, and srr7) and one was at position 1163 (Cys to Phe) (srr18) in the S2 subunit. The receptor-binding activity examined by a virus overlay protein blot assay and by a coimmunoprecipitation assay showed that srr11 S protein had extremely reduced binding activity, while the srr7 and srr18 proteins had binding activity similar to that of wild-type cl-2 protein. However, when cell surface receptors were used for the binding assay, all srr mutants showed activity similar to that of the wild type or only slightly reduced activity. These results, together with our previous observations, suggest that amino acids located at positions 62 to 65 of S1, a region conserved among the MHV strains examined, are important for receptor-binding activity. We also discuss the mechanism by which srr mutants with a mutation in S2 showed high resistance to neutralization by a soluble receptor, despite their sufficient level of binding to soluble receptors.",,"['Saeki, K', 'Ohtsuka, N', 'Taguchi, F']",,,,
,PMC,Hygromycin B resistance mediates elimination of Leishmania virus from persistently infected parasites.,,PMC230199,,,"A series of pX63-HYG derivatives encoding Leishmania RNA virus 1-4 (LRV1-4) sequences were electroporated into cells of Leishmania strain M4147, a virus-infected strain of L. guyanensis. After 6 weeks of drug selection (hygromycin B), transfected parasites lacked detectable quantities of viral genomic double-stranded RNA, viral capsid protein, and RNA-dependent RNA polymerase (RDRP) activity. Evidence of viral infection was not recovered upon removal of the drug. While viral RNA transcripts were produced from electroporated expression vectors, as determined by reverse transcription-PCR, viral antigens were not detected, suggesting that the antiviral effects of hygromycin B are mediated through translation inhibition. A short-term selection study suggests that the LRV1-4 elimination may not only be a function of hygromycin B as a protein synthesis inhibitor but also possibly related to the mechanism of hygromycin B resistance in Leishmania strains.",,"['Ro, Y T', 'Scheffter, S M', 'Patterson, J L']",,,,
,PMC,Prospective case-control study of role of infection in patients who reconsult after initial antibiotic treatment for lower respiratory tract infection in primary care.,,PMC2127769,,,"OBJECTIVE: To assess direct and indirect evidence of active infection which may benefit from further antibiotics in adults who reconsult within 4 weeks of initial antibiotic management of acute lower respiratory tract infection in primary care. DESIGN: Observational study with a nested case-control group. SETTING: Two suburban general practices in Arnold, Nottingham, over 7 winter months. SUBJECTS: 367 adults aged 16 years and over fulfilling a definition of lower respiratory tract infection and treated with antibiotics. 74 (20%) patients who reconsulted within 4 weeks for the same symptoms and 82 ""control"" patients who did not were investigated in detail at fallow up. MAIN OUTCOME MEASURES: Direct and indirect evidence of active infection at the time of the reconsultation or the follow up visit with the research nurse for the controls. Investigations performed included sputum culture, pneumococcal antigen detection, serial serology for viral and atypical pathogens and C reactive protein, throat swabs for detecting viral and atypical pathogens by culture and polymerase chain reaction, and chest radiographs. RESULTS: Demographic and clinical features of the groups were similar. Two thirds of the 74 patients who reconsulted received another antibiotic because the general practitioner suspected continuing infection. Any evidence of infection warranting antibiotic treatment was uncommon at reconsultation. The findings for the two groups were similar for the occurrence of identified pathogens; chest x ray changes of infection (present in 13%); and C reactive protein concentrations, which had nearly all fallen towards normal. Only three patients in the reconsultation group had concentrations > or = 40 mg/l. Pathogens identified at follow up in the 156 patients in both groups included ampicillin sensitive bacteria in six. Atypical infections diagnosed in 27 (Chlamydia pneumoniae in 22) and viral infections in 54 had probably been present at the initial presentation. CONCLUSION: Our study suggests that active infection, which may benefit from further antibiotics, is uncommon in patients who reconsult after a lower respiratory tract infection, and a repeat antibiotic prescription should be the exception rather than the rule. Other factors, such as patients' perception of their illness, may be more important than disease and infection in their decision to reconsult.",,"['Macfarlane, J.', 'Prewett, J.', 'Rose, D.', 'Gard, P.', 'Cunningham, R.', 'Saikku, P.', 'Euden, S.', 'Myint, S.']",,,,
,PMC,Influence of patients' expectations on antibiotic management of acute lower respiratory tract illness in general practice: questionnaire study.,,PMC2127752,,,"OBJECTIVE: To assess patients' views and expectations when they consult their general practitioner with acute lower respiratory symptoms and the influence these have on management. DESIGN: General practitioners studied consecutive, previously well adults and recorded clinical data, the certainty regarding their prescribing decision, and the influence of non-clinical factors on that decision. Patients completed a questionnaire at home after the consultation. SETTING: 76 doctors from suburban, inner city, and rural practices. SUBJECTS: 1014 eligible patients entered; 787 (78%) returned the questionnaire. MAIN OUTCOME MEASURES: The views of the patient, the views of and antibiotic prescription by the doctor. RESULTS: Most patients thought that their symptoms were caused by an infection (662) and that antibiotics would help (656) and had both wanted (564) and expected (561) such a prescription. 146 requested an antibiotic, 587 received one. Of the 643 patients who thought they had an infection, 582 wanted an antibiotic and thought it would help. Severity of symptoms did not relate to wanting antibiotics. For those prescribed antibiotics, their doctor thought they were definitely indicated in only 116 cases and not indicated in 126. Patient pressure most commonly influenced the decision to prescribe even when the doctor thought antibiotics were not indicated. Doctors considered antibiotics definitely indicated in only 1% of the group in whom patient pressure influenced the prescribing decision. Patients who did not receive an antibiotic that they wanted were much more likely to express dissatisfaction. Dissatisfied patients reconsulted for the same symptoms twice as often as satisfied patients. CONCLUSION: Patients presenting with acute lower respiratory symptoms often believe that infection is the problem and antibiotics the answer. Patients' expectations have a significant influence on prescribing, even when their doctor judges that antibiotics are not indicated.",,"['Macfarlane, J.', 'Holmes, W.', 'Macfarlane, R.', 'Britten, N.']",,,,
,PMC,Expression cloning and humoral immune response to the nucleocapsid and membrane proteins of equine arteritis virus.,,PMC170634,,,"To provide a convenient and sensitive method for the detection of equine arteritis virus (EAV)-specific serum antibodies, we developed an immunoblot assay employing the EAV nucleocapsid (N) and membrane (M) proteins expressed in a procaryotic expression vector (pMAL-c2) for the production of recombinant maltose-binding (MBP) fusion proteins (MBP-N and MBP-M). The antigenic reactivity of the recombinant fusion proteins and their Xa factor cleavage EAV products was confirmed by immunoblot using horse antisera to EAV. Some horse sera, however, showed immune reactivity to the MBP fusion partner protein. Based on a total of 32 horse sera analyzed for the presence of EAV antibodies by immunoblot, using the MBP-N or -M fusion proteins and the Xa factor cleavage EAV products, and in the serum neutralization test, there was 100% concordance between the assays. Sera from horses experimentally infected with EAV were reactive in the immunoblot test with both the MBP-N and the MBP-M fusion proteins by day 14 after EAV exposure. The reactivity continued to the end of the experiment at day 145 after infection. This immune reactivity correlated with the detection of neutralizing antibodies in the serum samples. Based on these findings, the recombinant N and M proteins might be useful for serodetection of EAV-infected animals.",,"['Kheyar, A', 'Martin, S', 'St-Laurent, G', 'Timoney, P J', 'McCollum, W H', 'Archambault, D']",,,,
,PMC,"Application of immunohistochemistry and in situ hybridization for detection of bovine coronavirus in paraffin-embedded, formalin-fixed intestines.",,PMC230096,,,A monoclonal antibody (MAb) (Z3A5) against spike protein subunit of bovine coronavirus (BCV) reacted with the virus in formalin-fixed intestines in an immunoperoxidase test. We found an 88% correlation between immunohistochemistry with Z3A5 and in situ hybridization with a BCV nucleoprotein cDNA probe. MAb Z3A5 reacted with 90 BCV isolates from the United States and was an effective reagent for the diagnosis of BCV.,,"['Zhang, Z', 'Andrews, G A', 'Chard-Bergstrom, C', 'Minocha, H C', 'Kapil, S']",,,,
,PMC,Isolation and characterization of a coronavirus from elk calves with diarrhea.,,PMC230091,,,"This is the first report of the isolation of a coronavirus from elk calves. Two fecal samples from elk calves with diarrhea were shown to be positive for coronavirus-like particles by electron microscopy, and the particles were propagated in the human rectal tumor-18 cell line. After 24 h, syncytia were observed, and cell culture supernatants from both samples showed hemagglutinating activity with mouse erythrocytes. Cells infected with both elk coronavirus (ECV) isolates reacted with Z3A5, a monoclonal antibody against the spike protein of bovine coronavirus (BCV), on an indirect fluorescent antibody test. The protein profiles of both ECV isolates were similar to that of BCV as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. On Northern blot analysis, the transcriptional pattern of ECV was typical of coronaviruses, with a nested set of transcripts with common 3' end sequences. Based on a published nucleoprotein gene sequence for BCV (Mebus isolate), we arbitrarily designed two primers for amplification by PCR. After cloning, the nucleoprotein was sequenced and a high degree of homology (99%) between the nucleoprotein gene sequences of ECV and BCV was observed. Thus, ECV is closely related genetically and antigenically to BCV and will be a new member of antigenic group 2 of the mammalian coronaviruses, which possess hemagglutinin-esterase protein.",,"['Majhdi, F', 'Minocha, H C', 'Kapil, S']",,,,
,PMC,Seroprevalence of Bartonella henselae infection and correlation with disease status in cats in Switzerland.,,PMC230080,,,"The prevalence of infection with Bartonella henselae was investigated in cats from different areas of Switzerland. Serum samples of 728 cats were examined for antibodies to B. henselae by immunofluorescent antibody testing, and the results were analyzed with a view to a possible correlation between a positive titer and signalment, clinical signs, infection with feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), feline coronavirus (FCoV), or feline spumavirus (FeSFV), and the living environments of the cats. The seroprevalence in all cats was 8.3%. No significantly different prevalence was found in sick versus healthy cats (9.2 versus 7.2%); however, in sick cats seropositive for B. henselae, there was an increased frequency of stomatitis and a variety of diseases of the kidneys and the urinary tract. There was an increased prevalence of B. henselae in cats positive for FCoV (P = 0.0185) or FeSFV (P = 0.0235) and no statistically significant increased prevalence in cats infected with FeLV or FIV. There was no correlation between a positive titer and sex or breed. The same prevalence of B. henselae antibodies was found in cats with and without access to the outdoors and in cats from single- and multicat households. The seroprevalence was increased in cats living south of the Alps (12.1%); however, this difference was not significant (P = 0.0616).",,"['Glaus, T', 'Hofmann-Lehmann, R', 'Greene, C', 'Glaus, B', 'Wolfensberger, C', 'Lutz, H']",,,,
,PMC,Frequency and natural history of rhinovirus infections in adults during autumn.,,PMC230076,,,"Human rhinovirus (HRV) accounts for a significant portion of common-cold illness, with the peak incidence being in the early fall. Three hundred forty-six adults who had self-diagnosed colds of 48 h or less were enrolled in a study during September and October 1994 to determine the frequency and clinical course of HRV infections. Nasal wash specimens for viral culture and reverse transcription-PCR (RT-PCR) for HRV RNA and human coronavirus OC43 and 229E RNA detection were collected on enrollment, and participants recorded their symptoms twice daily for 14 days. Middle ear pressure (MEP) was measured with a digital tympanometer on days 1 and 7. Picornaviruses (224 HRV and 7 enterovirus isolates) were detected by culture in 67% (231 of 346) of the subjects. Among 114 samples negative by culture, HRV was detected by RT-PCR in 52 (46%) for an overall picornavirus infection rate of 82% (283 of 346 subjects). Among the remaining 62 negative samples, human coronavirus RNA was detected by RT-PCR in 5 patients, so that 288 (83%) of patients had documented viral infection. The first symptom noticed most often was sore throat (40%) in HRV culture- or PCR-positive patients and stuffy nose in HRV-negative patients (27%). No differences in symptom scores over time or in the presence of individual symptoms were noted between groups. The median duration of the cold episodes was 11 days in HRV culture-positive patients, 9.5 days in HRV RT-PCR-positive patients, and 11.5 days in HRV-negative patients. On enrollment, abnormal MEPs (< or = -100 or > or = +100 mm of H2O) were found for 21% of HRV culture-positive patients, 14% of HRV RT-PCR-positive patients, and 10% of HRV-negative patients. No important differences in the clinical course of HRV culture-positive, HRV culture-negative and RT-PCR-positive, or HRV-negative colds were found. These results represent the highest frequency of virologically confirmed natural colds to date and document the importance of rhinoviruses as the cause of colds during fall months.",,"['Arruda, E', 'Pitkäranta, A', 'Witek, T J', 'Doyle, C A', 'Hayden, F G']",,,,
,PMC,Mouse susceptibility to mouse hepatitis virus infection is linked to viral receptor genotype.,,PMC192354,,,"We have reported that the receptor for mouse hepatitis virus (MHV) expressed in MHV-susceptible BALB/c mice (MHVR1) has 10 to 30 times the virus-binding activity of the MHV receptor expressed in MHV-resistant SJL mice (MHVR2) (N. Ohtsuka, Y. K. Yamada, and F. Taguchi, J. Gen. Virol. 77:1683-1992, 1996). This fact indicates the possibility that the difference in MHV susceptibility between BALB/c and SJL mice is determined by the virus-binding activity of the receptor. To test this possibility, we have examined MHV susceptibility in mice with the homozygous MHVR1 gene (R1/R1 genotype), mice with the MHVR1 and MHVR2 genes (R1/R2 genotype), and mice with the homozygous MHVR2 gene (R2/R2 genotype) produced by cross and backcross mating between BALB/c and SJL mice. All 63 F2 and backcrossed mice with the MHVR1 gene (R1/R1 and R1/R2) were susceptible to MHV infection, and all 57 with the homozygous MHVR2 gene (R2/R2) were resistant. We have also examined the MHV receptor genotypes of several mouse strains that were reported to be susceptible to MHV infection. All of those mice had the MHVR1 gene. These results suggest the possibility that the viral receptor determines the susceptibility of the whole animal to MHV infection.",,"['Ohtsuka, N', 'Taguchi, F']",,,,
,PMC,Rotavirus virus-like particles administered mucosally induce protective immunity.,,PMC192335,,,"We have evaluated the immunogenicity and protective efficacy of rotavirus subunit vaccines administered by mucosal routes. Virus-like particles (VLPs) produced by self-assembly of individual rotavirus structural proteins coexpressed by baculovirus recombinants in insect cells were the subunit vaccine tested. We first compared the immunogenicities and protective efficacies of VLPs containing VP2 and VP6 (2/6-VLPs) and G3 2/6/7-VLPs mixed with cholera toxin and administered by oral and intranasal routes in the adult mouse model of rotavirus infection. VLPs administered orally induced serum antibody and intestinal immunoglobulin A (IgA) and IgG. The highest oral dose (100 microg) of VLPs induced protection from rotavirus challenge (> or = 50% reduction in virus shedding) in 50% of the mice. VLPs administered intranasally induced higher serum and intestinal antibody responses than VLPs administered orally. All mice receiving VLPs intranasally were protected from challenge; no virus was shed after challenge. Since there was no difference in immunogenicity or protective efficacy between 2/6- and 2/6/7-VLPs, protection was achieved without inclusion of the neutralization antigens VP7 and VP4. We also tested the immunogenicities and protective efficacies of 2/6-VLPs administered intranasally without the addition of cholera toxin. 2/6-VLPs administered intranasally without cholera toxin induced lower serum and intestinal antibody titers than 2/6-VLPs administered with cholera toxin. The highest dose (100 microg) of 2/6-VLPs administered intranasally without cholera toxin resulted in a mean reduction in shedding of 38%. When cholera toxin was added, higher levels of protection were achieved with 10-fold less immunogen. VLPs administered mucosally offer a promising, safe, nonreplicating vaccine for rotavirus.",,"[""O'Neal, C M"", 'Crawford, S E', 'Estes, M K', 'Conner, M E']",,,,
,PMC,"Structure-function analysis of the gE-gI complex of feline herpesvirus: mapping of gI domains required for gE-gI interaction, intracellular transport, and cell-to-cell spread.",,PMC192302,,,"Alphaherpesvirus glycoproteins gE and gI form a noncovalently associated hetero-oligomeric complex, which is involved in cell-to-cell spread. In the absence of gI, feline herpesvirus (FHV) gE is transport incompetent and fully retained in the endoplasmic reticulum. Here, we assess the effect of progressive C-terminal truncations of FHV gI on the biosynthesis, intracellular transport, and function of the gE-gI complex. The truncated gI proteins were coexpressed with gE in the vaccinia virus-based vTF7-3 expression system. The results were corroborated and extended by studying FHV recombinants expressing truncated gI derivatives. The following conclusions can be drawn. (i) Deletion of the cytoplasmic tail, the transmembrane region plus the C-terminal half of the ectodomain of gI, does not affect intracellular transport of gE. Apparently, the N-terminal 166 residues of gI constitute a domain involved in gE-gI interaction. (ii) A region mediating stable association with gE is located within the N-terminal 93 residues of gI. (iii) The cytoplasmic domain of gI is not essential for gE-gI-mediated cell-to-cell transmission of FHV, as judged from plaque morphology. Deletion of the cytoplasmic tail of gI reduced plaque size by only 35%. (iv) Recombinants expressing the N-terminal 166 residues of gI display a small-plaque phenotype but produce larger plaques than recombinants with a disrupted gI gene. Thus, a complex consisting of gE and the N-terminal half of the gI ectodomain may retain residual biological activity. The implications of these findings for gE-gI interaction and function are discussed.",,"['Mijnes, J D', 'Lutters, B C', 'Vlot, A C', 'van Anken, E', 'Horzinek, M C', 'Rottier, P J', 'de Groot, R J']",,,,
,PMC,Rotavirus is released from the apical surface of cultured human intestinal cells through nonconventional vesicular transport that bypasses the Golgi apparatus.,,PMC192285,,,"Rotaviruses are nonenveloped viruses that infect enterocytes of the small intestine and cause severe infantile gastroenteritis. It was previously thought that rotavirus exits cells by lysis, but this behavior does not match the local pathogenesis of the virus. In this study, we have investigated the release of the simian rotavirus strain (RRV) from the polarized intestinal Caco-2 cells. We found that RRV is released almost exclusively from the apical pole of Caco-2 cells before any cells lyse. Using confocal laser scanning microscopy and drugs that inhibit vesicular transport, we studied the RRV transport route from the endoplasmic reticulum (ER) to the apical side of intestinal cells. We demonstrated that RRV exits from the ER through a carbonyl cyanide m-chlorophenylhydrazone-sensitive vesicular transport. RRV staining was never found within the Golgi apparatus or lysosomes, suggesting that the RRV intracellular pathway does not involve these organelles. This finding was confirmed by treatment with monensin or NH4Cl, which do not affect release of RRV. Electron microscopic analysis revealed RRV containing small smooth vesicles in the apical area and free virions outside the cell in the brush border, consistent with a vesicular vectorial transport of virus. These results may provide, for the first time, a cellular explanation of the pathogenesis of rotavirus.",,"['Jourdan, N', 'Maurice, M', 'Delautier, D', 'Quero, A M', 'Servin, A L', 'Trugnan, G']",,,,
,PMC,Heterogeneous Distribution of the Unusual Phospholipid  Semilysobisphosphatidic Acid through the Golgi Complex,,PMC25704,,,"To investigate the distribution of lipids through the Golgi complex, we analyzed the envelopes of several viruses that assemble in different subcompartments of the Golgi, as well as subcellular fractions. Our results indicate that each Golgi subcompartment has a distinct phospholipid composition due mainly to differences in the relative amounts of semilysobisphosphatidic acid (SLBPA), sphingomyelin, phosphatidylserine, and phosphatidylinositol. Interestingly, SLBPA is enriched in the adjacent Golgi networks compared with the Golgi stack, and this enrichment varies with cell type. The heterogeneous distribution of SLBPA through the Golgi complex suggests it may play an important role in the structure and/or function of this organelle.",,"['Cluett, Edward B.', 'Kuismanen, Esa', 'Machamer, Carolyn E.']",,,,
,PMC,Distinct Molecular Events during Secretory Granule Biogenesis  Revealed by Sensitivities to Brefeldin A,,PMC25700,,,"The biogenesis of peptide hormone secretory granules involves a series of sorting, modification, and trafficking steps that initiate in the trans-Golgi and trans-Golgi network (TGN). To investigate their temporal order and interrelationships, we have developed a pulse–chase protocol that follows the synthesis and packaging of a sulfated hormone, pro-opiomelanocortin (POMC). In AtT-20 cells, sulfate is incorporated into POMC predominantly on N-linked endoglycosidase H-resistant oligosaccharides. Subcellular fractionation and pharmacological studies confirm that this sulfation occurs at the trans-Golgi/TGN. Subsequent to sulfation, POMC undergoes a number of molecular events before final storage in dense-core granules. The first step involves the transfer of POMC from the sulfation compartment to a processing compartment (immature secretory granules, ISGs): Inhibiting export of pulse-labeled POMC by brefeldin A (BFA) or a 20°C block prevents its proteolytic conversion to mature adrenocorticotropic hormone. Proteolytic cleavage products were found in vesicular fractions corresponding to ISGs, suggesting that the processing machinery is not appreciably activated until POMC exits the sulfation compartment. A large portion of the labeled hormone is secreted from ISGs as incompletely processed intermediates. This unregulated secretory process occurs only during a limited time window: Granules that have matured for 2 to 3 h exhibit very little unregulated release, as evidenced by the efficient storage of the 15-kDa N-terminal fragment that is generated by a relatively late cleavage event within the maturing granule. The second step of granule biogenesis thus involves two maturation events: proteolytic activation of POMC in ISGs and a transition of the organelle from a state of high unregulated release to one that favors intracellular storage. By using BFA, we show that the two processes occurring in ISGs may be uncoupled: although the unregulated secretion from ISGs is impaired by BFA, proteolytic processing of POMC within this organelle proceeds unaffected. The finding that BFA impairs constitutive secretion from both the TGN and ISGs also suggests that these secretory processes may be related in mechanism. Finally, our data indicate that the unusually high levels of unregulated secretion often associated with endocrine tumors may result, at least in part, from inefficient storage of secretory products at the level of ISGs.",,"['Fernandez, Carlos J.', 'Haugwitz, Michael', 'Eaton, Benjamin', 'Moore, Hsiao-Ping H.']",,,,
,PMC,"Effects of inhaled histamine, methacholine and capsaicin on sputum levels of alpha 2-macroglobulin",,PMC1758451,,,"BACKGROUND: Plasma exudation-derived proteins and peptides contribute significantly to inflammation in the airway mucosa in vivo. In the guinea pig trachea both histamine and the neurogenic stimulant capsaicin produce acute mucosal tissue distribution and luminal entry of bulk plasma, whereas cholinergic agonists fail to produce this effect. Of these agents, only histamine induces mucosal exudation of plasma in human nasal airways. The exudative effect of the above agents on human bronchi remains unknown. METHODS: The bronchial exudative responses to inhalation of histamine, methacholine, and capsaicin were examined in two groups of healthy volunteers. Sputum was induced on three occasions in each study group by inhalation of hypertonic saline (4.5%) given as an aerosol for 40 minutes using an ultrasonic nebuliser. The second and third occasions were preceded by histamine and capsaicin challenges in the first study group, and by histamine and methacholine challenges in the second study group. Histamine and methacholine were given in cumulative doses (total doses 3160 micrograms, respectively) or until a 20% reduction in forced expiratory volume in one second (FEV1) was achieved. Cumulative doses of capsaicin were inhaled until coughing prevented the subjects from drawing a full breath. Sputum levels of alpha 2-macroglobulin (729 kDa) were measured as an index of mucosal exudation of bulk plasma. RESULTS: Histamine increased mean (SE) sputum levels of alpha 2-macroglobulin from 2.72 (1.01) micrograms/ml (95% confidence interval (CI) 0.49 to 4.94) to 18.38 (8.03) micrograms/ml (95% CI 0.49 to 36.27) in the first group, and from 1.66 (0.84) micrograms/ml (95% CI -0.18 to 3.49) to 9.43 (3.63) micrograms/ml (95% CI 1.59 to 17.27) in the second group. In contrast, capsaicin evoked no exudation (sputum levels of alpha 2- macroglobulin 1.21 (0.28) micrograms/ml (95% CI 0.59 to 1.83)) and methacholine produced a minor increase in sputum levels of alpha 2- macroglobulin (2.90 (0.92) micrograms/ml (95% CI 0.90 to 4.89)). CONCLUSIONS: These results indicate that histamine is a useful agent for studying bronchial exudative responsiveness in man and that exudative effects are only of marginal importance in the cough and bronchoconstriction produced by capsaicin and methacholine.",,"['Halldorsdottir, H.', 'Greiff, L.', 'Wollmer, P.', 'Andersson, M.', 'Svensson, C.', 'Alkner, U.', 'Persson, C. G.']",,,,
,PMC,Effectiveness of influenza vaccination policy at targeting patients at high risk of complications during winter 1994-5: cross sectional survey.,,PMC2127699,,,,,"Watkins, J.",,,,
,PMC,Randomised controlled trial of a general practice programme of home based exercise to prevent falls in elderly women.,,PMC2127698,,,"OBJECTIVE: To assess the effectiveness of a home exercise programme of strength and balance retraining exercises in reducing falls and injuries in elderly women. DESIGN: Randomised controlled trial of an individually tailored programme of physical therapy in the home (exercise group, n = 116) compared with the usual care and an equal number of social visits (control group, n = 117). SETTING: 17 general practices in Dunedin, New Zealand. SUBJECTS: Women aged 80 years and older living in the community and registered with a general practice in Dunedin. MAIN OUTCOME MEASURES: Number of falls and injuries related to falls and time between falls during one year of follow up; changes in muscle strength and balance measures after six months. RESULTS: After one year there were 152 falls in the control group and 88 falls in the exercise group. The mean (SD) rate of falls was lower in the exercise than the control group (0.87 (1.29) v 1.34 (1.93) falls per year respectively; difference 0.47; 95% confidence interval 0.04 to 0.90). The relative hazard for the first four falls in the exercise group compared with the control group was 0.68 (0.52 to 0.90). The relative hazard for a first fall with injury in the exercise group compared with the control group was 0.61 (0.39 to 0.97). After six months, balance had improved in the exercise group (difference between groups in change in balance score 0.43 (0.21 to 0.65). CONCLUSIONS: An individual programme of strength and balance retraining exercises improved physical function and was effective in reducing falls and injuries in women 80 years and older.",,"['Campbell, A. J.', 'Robertson, M. C.', 'Gardner, M. M.', 'Norton, R. N.', 'Tilyard, M. W.', 'Buchner, D. M.']",,,,
,PMC,"Acute viral infections of upper respiratory tract in elderly people living in the community: comparative, prospective, population based study of disease burden.",,PMC2127683,,,"OBJECTIVE: To evaluate the disease burden of upper respiratory infections in elderly people living at home. DESIGN: Prospective surveillance of elderly people. INTERVENTION: None. SETTING: Leicestershire, England SUBJECTS: 533 subjects 60 to 90 years of age. MAIN OUTCOME MEASURES: Pathogens, symptoms, restriction of activity, duration of illness, medical consultations, interval between onset of illness and medical consultation, antibiotic use, admission to hospital, and death. RESULTS: 231 pathogens were identified for 211 (43%) of 497 episodes for which diagnostic specimens were available: 121 (52%) were rhinoviruses, 59 (26%) were coronaviruses, 22 (9.5%) were influenza A or B, 17 (7%) were respiratory syncytial virus, 7 (3%) were parainfluenza viruses, and 3 (1%) were Chlamydia species; an adenovirus and Mycoplasma pneumoniae caused one infection each. Infections occurred at a rate of 1.2 episodes per person per annum (95% confidence interval 1.0 to 1.7; range 0-10) and were clinically indistinguishable. Lower respiratory tract symptoms complicated 65% of upper respiratory infections and increased the medical consultation rate 2.4-fold (chi 2 test P < 0.001). The median interval between onset of illness and medical consultation was 3 days for influenza and 5 days for other infections. Rhinoviruses caused the greatest disease burden overall followed by episodes of unknown aetiology, coronaviruses, influenza A and B, and respiratory syncytial virus. CONCLUSIONS: Respiratory viruses cause substantial morbidity in elderly people. Although respiratory syncytial virus and influenza cause considerable individual morbidity, the burden of disease from rhinovirus infections and infections of unknown aetiology seems greater overall. The interval between onset of illness and consultation together with diagnostic difficulties raises concern regarding the role of antiviral drugs in treating influenza.",,"['Nicholson, K. G.', 'Kent, J.', 'Hammersley, V.', 'Cancio, E.']",,,,
,PMC,Prevalence of coronavirus antibodies in Iowa swine.,,PMC1189426,,,"Three hundred and forty-seven serum samples from 22 Iowa swine herds were screened for TGEV/PRCV neutralizing antibody. Ninety-one percent of the sera and all 22 herds were positive. These sera were then tested by the blocking ELISA test to distinguish TGEV and PRCV antibody. The ELISA test confirmed the high percentage of TGEV/PRCV positive sera. By the blocking ELISA test, 12 herds were PRCV positive, 6 herds were TGEV positive and 4 herds were mixed with sera either positive for TGEV or PRCV antibody. The results suggest a recent increase in TGEV/PRCV seroprevalence in Iowa swine most likely due to subclinical PRCV infections.",,"['Wesley, R D', 'Woods, R D', 'McKean, J D', 'Senn, M K', 'Elazhary, Y']",,,,
,PMC,Uses of inorganic hypochlorite (bleach) in health-care facilities.,,PMC172936,,,"Hypochlorite has been used as a disinfectant for more than 100 years. It has many of the properties of an ideal disinfectant, including a broad antimicrobial activity, rapid bactericidal action, reasonable persistence in treated potable water, ease of use, solubility in water, relative stability, relative nontoxicity at use concentrations, no poisonous residuals, no color, no staining, and low cost. The active species is undissociated hypochlorous acid (HOCl). Hypochlorites are lethal to most microbes, although viruses and vegetative bacteria are more susceptible than endospore-forming bacteria, fungi, and protozoa. Activity is reduced by the presence of heavy metal ions, a biofilm, organic material, low temperature, low pH, or UV radiation. Clinical uses in health-care facilities include hyperchlorination of potable water to prevent Legionella colonization, chlorination of water distribution systems used in hemodialysis centers, cleaning of environmental surfaces, disinfection of laundry, local use to decontaminate blood spills, disinfection of equipment, decontamination of medical waste prior to disposal, and dental therapy. Despite the increasing availability of other disinfectants, hypochlorites continue to find wide use in hospitals.",,"['Rutala, W A', 'Weber, D J']",,,,
,PMC,Role of spleen macrophages in innate and acquired immune responses against mouse hepatitis virus strain A59.,,PMC1364066,,,"Owing to their scavenging and phagocytic functions, spleen macrophages are regarded to be important in the induction and maintenance of both innate and acquired immune defence mechanisms. In this study, we investigated the role of spleen macrophages in immunity against mouse hepatitis virus strain A59 (MHV-A59). Previous studies showed that spleen and liver macrophages are the first target cells for infection by MHV-A59 in vivo, suggesting that they could be involved in the induction of immune responses against MHV-A59. We used a macrophage depletion technique to deplete macrophages in vivo and studied the induction of virus-specific antibody and cytotoxic T-cell (CTL) responses and non-immune resistance against MHV-A59 in normal and macrophage-depleted mice. Virus titres in spleen and liver increased rapidly in macrophage-depleted mice, resulting in death of mice within 4 days after infection. Elimination of macrophages before immunization with MHV-A59 resulted in increased virus-specific humoral and T-cell proliferative responses. However, virus-specific CTL responses were not altered in macrophage-depleted mice. Our results show that spleen macrophages are of major importance as scavenger cells during MHV-A59 infection and are involved in clearance of virus from the host. In addition, macrophages may be involved in the regulation of acquired immune responses. In the absence of macrophages, increased virus-specific T-cell and antibody responses are detectable, suggesting that macrophages suppress MHV-A59-specific T- and B-cell responses and that other cells serve as antigen-presenting cells.",,"['Wijburg, O L', 'Heemskerk, M H', 'Boog, C J', 'Van Rooijen, N']",,,,
,PMC,Risk of Upper Respiratory Tract Infection in Athletes: An Epidemiologic and Immunologic Perspective,,PMC1320353,,,"OBJECTIVE: The chronic and acute immune responses to both heavy and moderate exercise are reviewed, with guidelines provided for the prevention and management of upper respiratory tract infection (URTI) in athletes. DATA SOURCES: Epidemiologic and experimental exercise immunology research data were used. The MEDLINE database was searched for the years 1970 to 1997 with the terms “exercise,” “immune,” “infection,” “lymphocyte,” and “neutrophil.” DATA SYNTHESIS: A descriptive review with summary figures and one table. CONCLUSIONS/RECOMMENDATIONS: The epidemiologic data suggest that endurance athletes are at increased risk for URTI during periods of heavy training and the 1-to 2-week period after marathon-type race events. Several researchers have reported a diminished neutrophil function in athletes during periods of intense and heavy training. Following each bout of prolonged heavy endurance exercise, several components of the immune system appear to demonstrate suppressed function for several hours. This has led to the concept of the “open window,” described as the 3- to 12-hour time period after prolonged endurance exercise when host defense is decreased and the risk of URTI is elevated. There is sufficient evidence for sports medicine professionals to encourage athletes to practice various hygienic measures to lower their risk of URTI and to avoid heavy exertion during systemic illness.",,"Nieman, David C.",,,,
,PMC,The carboxyl-terminal 120-residue polypeptide of infectious bronchitis virus nucleocapsid induces cytotoxic T lymphocytes and protects chickens from acute infection.,,PMC192145,,,"Specific cytotoxic T-lymphocyte (CTL) responses to nucleocapsid of infectious bronchitis virus (IBV) were identified by using target cells infected with a Semliki Forest virus (SFV) vector. Effector cells for CTL assays were collected from chickens infected with the Gray strain of IBV or inoculated with a DNA plasmid encoding nucleocapsid proteins. IBV-specific CTL epitopes were mapped within the carboxyl-terminal 120 amino acids of the nucleocapsid protein. CTL lysis of target cells infected with SFV encoding nucleocapsid was major histocompatibility complex restricted and mediated by CD8+ T cells. In addition, splenic T cells collected from chickens inoculated in the breast muscle with a DNA plasmid encoding this CTL epitope(s) recognized target cells infected with wild-type virus or an SFV vector encoding nucleocapsid proteins. CTL activity of splenic T cells collected from chicks immunized with a DNA plasmid encoding CTL epitopes was cross-reactive, in that lysis of target cells infected with serologically distinct strains of IBV was dose responsive in a manner similar to that for lysis of target cells infected with the homologous strain of IBV. Furthermore, chickens immunized with a DNA plasmid encoding a CTL epitope(s) were protected from acute viral infection.",,"['Seo, S H', 'Wang, L', 'Smith, R', 'Collisson, E W']",,,,
,PMC,Coronavirus genomic and subgenomic minus-strand RNAs copartition in membrane-protected replication complexes.,,PMC192126,,,"The majority of porcine transmissible gastroenteritis coronavirus plus-strand RNAs (genome and subgenomic mRNAs), at the time of peak RNA synthesis (5 h postinfection), were not found in membrane-protected complexes in lysates of cells prepared by Dounce homogenization but were found to be susceptible to micrococcal nuclease (85%) or to sediment to a pellet in a cesium chloride gradient (61%). They therefore are probably free molecules in solution or components of easily dissociable complexes. By contrast, the majority of minus-strand RNAs (genome length and subgenomic mRNA length) were found to be resistant to micrococcal nuclease (69%) or to remain suspended in association with membrane-protected complexes following isopycnic sedimentation in a cesium chloride gradient (85%). Furthermore, 35% of the suspended minus strands were in a dense complex (1.20 to 1.24 g/ml) that contained an RNA plus-to-minus-strand molar ratio of approximately 8:1 and viral structural proteins S, M, and N, and 65% were in a light complex (1.15 to 1.17 g/ml) that contained nearly equimolar amounts of plus- and minus-strand RNAs and only trace amounts of proteins M and N. In no instance during fractionation were genome-length minus strands found segregated from sub-genome-length minus strands. These results indicate that all minus-strand species are components of similarly structured membrane-associated replication complexes and support the concept that all are active in the synthesis of plus-strand RNAs.",,"['Sethna, P B', 'Brian, D A']",,,,
,PMC,Characterization of an endoplasmic reticulum retention signal in the rubella virus E1 glycoprotein.,,PMC192117,,,"Rubella virus contains three structural proteins, capsid, E2, and E1. E2 and E1 are type I membrane glycoproteins that form a heterodimer in the endoplasmic reticulum (ER) before they are transported to and retained in the Golgi complex, where virus assembly occurs. The bulk of unassembled E2 and E1 subunits are not transported to the Golgi complex. We have recently shown that E2 contains a Golgi-targeting signal that mediates retention of the E2-E1 complex (T. C. Hobman, L. Woodward, and M. G. Farquhar, Mol. Biol. Cell 6:7-20, 1995). The focus of this study was to determine if E1 glycoprotein also contains intracellular targeting information. We constructed a series of chimeric reporter proteins by fusing domains from E1 to the ectodomains of two other type I membrane proteins which are normally transported to the cell surface, vesicular stomatitis virus G protein (G) and CD8. Fusion of the E1 transmembrane and cytoplasmic regions, but not analogous domains from two control membrane proteins, to the ectodomains of G and CD8 proteins caused the resulting chimeras to be retained in the ER. Association of the ER-retained chimeras with known ER chaperone proteins was not detected. ER localization required both the transmembrane and cytoplasmic regions of E1, since neither of these domains alone was sufficient to retain the reporter proteins. Increasing the length of the E1 cytoplasmic domain by 10 amino acids completely abrogated ER retention. This finding also indicated that the chimeras were not retained as a result of misfolding. In summary, we have identified a new type of ER retention signal that may function to prevent unassembled E1 subunits and/or immature E2-E1 dimers from reaching the Golgi complex, where they could interfere with viral assembly. Accordingly, assembly of E2 and E1 would mask the signal, thereby allowing transport of the heterodimer from the ER.",,"['Hobman, T C', 'Lemon, H F', 'Jewell, K']",,,,
,PMC,Cytotoxic T-cell-resistant variants arise at early times after infection in C57BL/6 but not in SCID mice infected with a neurotropic coronavirus.,,PMC192113,,,"Under certain conditions, C57BL/6 mice persistently infected with mouse hepatitis virus strain JHM (MHV-JHM) develop clinical disease and histological evidence of demyelination several weeks after inoculation with virus. In a previous report, we showed that mutations in the RNA encoding an immunodominant CD8 T-cell epitope within the surface glycoprotein (epitope S-510-518) were present in all persistently infected animals and that these mutations abrogated recognition by virus-specific cytotoxic T cells (CTLs) in direct ex vivo cytotoxicity assays. To obtain further evidence that these mutations were necessary for the development of clinical disease, the temporal course of their appearance was determined. Mutations in the epitope were identified by 10 to 12 days after inoculation, and in some mice, virus containing mutated epitope was the dominant species detected by 15 days. In addition, most mice that remain asymptomatic at 80 days after inoculation, a time after which clinical disease almost never develops, were infected with only wild-type virus. Finally, analysis of virus isolated from mice with severe combined immunodeficiency (SCID) revealed the presence only of wild-type epitope S-510-518. These results, by showing that mutations are not selected in SCID mice and occur at early times after inoculation in C57BL/6 mice, support the view that they result from immune pressure and contribute to virus persistence and demyelination in mice infected persistently with MHV-JHM.",,"['Pewe, L', 'Xue, S', 'Perlman, S']",,,,
,PMC,A bulged stem-loop structure in the 3' untranslated region of the genome of the coronavirus mouse hepatitis virus is essential for replication.,,PMC192104,,,"The 3' untranslated region (UTR) of the positive-sense RNA genome of the coronavirus mouse hepatitis virus (MHV) contains sequences that are necessary for the synthesis of negative-strand viral RNA as well as sequences that may be crucial for both genomic and subgenomic positive-strand RNA synthesis. We have found that the entire 3' UTR of MHV could be replaced by the 3' UTR of bovine coronavirus (BCV), which diverges overall by 31% in nucleotide sequence. This exchange between two viruses that are separated by a species barrier was carried out by targeted RNA recombination. Our results define regions of the two 3' UTRs that are functionally equivalent despite having substantial sequence substitutions, deletions, or insertions with respect to each other. More significantly, our attempts to generate an unallowed substitution of a particular portion of the BCV 3' UTR for the corresponding region of the MHV 3' UTR led to the discovery of a bulged stem-loop RNA secondary structure, adjacent to the stop codon of the nucleocapsid gene, that is essential for MHV viral RNA replication.",,"['Hsue, B', 'Masters, P S']",,,,
,PMC,Vaccinia virus membrane proteins p8 and p16 are cotranslationally inserted into the rough endoplasmic reticulum and retained in the intermediate compartment.,,PMC192086,,,"The use of two-dimensional gel electrophoresis has identified the gene products A14L (p16) and A13L (p8) as abundant membrane proteins of the first infectious form of vaccinia virus, the intracellular mature virus (IMV; O. N. Jensen, T. Houthaeve, A. Shevchenko, S. Cudmore, T. Ashford, M. Mann, G. Griffiths, J. Krijnse Locker, J. Virol. 70:7485-7497, 1996). In this study, these two proteins were characterized in detail. In infected cells, both proteins localize not only to the viral membranes but also to tubular-cisternal membranes of the intermediate compartment, defined by the use of antibodies to either rab1A or p21, which colocalize with rab1A (J. Krijnse Locker, S. Schleich, D. Rodriguez, B. Goud, E. J. Snijder, and G. Griffiths, J. Biol. Chem. 271:14950-14958, 1996). Both proteins appear to reach this destination via cotranslational insertion into the rough endoplasmic reticulum, as shown by in vitro translation and translocation experiments. Whereas p16 probably spans the membrane twice, p8 is inserted into the membrane by means of its single NH2-terminal hydrophobic domain, adopting a topology which leaves the C terminus exposed to the cytoplasm. Combined immunocytochemical and biochemical data show that p16 is a member of the inner of the two IMV membrane layers, whereas p8 localizes to both the inner and the outer membrane. These findings are discussed with respect to our model of IMV membrane assembly.",,"['Salmons, T', 'Kuhn, A', 'Wylie, F', 'Schleich, S', 'Rodriguez, J R', 'Rodriguez, D', 'Esteban, M', 'Griffiths, G', 'Locker, J K']",,,,
,PMC,Ambisense gene expression from recombinant rabies virus: random packaging of positive- and negative-strand ribonucleoprotein complexes into rabies virions.,,PMC192070,,,"We have recovered from cDNA a rabies virus (RV) containing identical, transcriptionally active promoters at its genome (negative-strand) and antigenome RNA and directing efficient expression of a chloramphenicol acetyltransferase (CAT) reporter gene from the antigenome. Transcription of the antigenome CAT gene was terminated by a modified RV gene junction able to mediate transcription stop and polyadenylation but not reinitiation of downstream transcripts. While in standard RV-infected cells genome and antigenome RNAs were present in a 49:1 ratio, the ambisense virus directed synthesis of equal amounts of genome and antigenome RNA (1:1). Total replicative synthesis was reduced by a factor of less than 2, revealing an unexpectedly high level of replication activity of the transcriptionally active promoter in the absence of the parental antigenome promoter. Successful packaging of ambisense ribonucleoprotein complexes (RNPs) into virions demonstrated that the parental 5' end of the RV genome RNA does not contain putative signals required for incorporation into virions. As determined both for standard RV and ambisense RV, virus particles contained genome and antigenome RNPs in the same ratios as those present in infected cells (49:1 and 1:1, respectively), indicating indiscriminate incorporation of RNPs independent of signals in the RNA. Ambisense expression of multiple foreign genes from RV vectors may circumvent problems with transcriptional attenuation of rhabdovirus housekeeping genes.",,"['Finke, S', 'Conzelmann, K K']",,,,
,PMC,The ectodomain of the human T-cell leukemia virus type 1 TM glycoprotein is involved in postfusion events.,,PMC192057,,,"To examine the contribution of the transmembrane envelope glycoprotein (TM) to the infectivity of the human T-cell leukemia virus type 1 (HTLV-1), single amino acid substitutions were introduced throughout its ectodomain. The mutated envelopes were tested for intracellular maturation and for functions, including ability to elicit syncytium formation and ability to mediate cell-to-cell transmission of the virus. Three major phenotypes, defining three functionally distinct regions, were identified. (i) Mutations causing defects in intracellular maturation of the envelope precursor are mostly distributed in the central portion of the TM ectodomain, containing the immunosuppressive peptide. This region, which includes vicinal cysteines thought to form an intramolecular disulfide bridge, is probably essential for correct folding of the protein. (ii) Mutations resulting in reduced syncytium-forming ability despite correct intracellular maturation are clustered in the amino-terminal part of the TM ectodomain, within the leucine zipper-like motif. Similar motifs with a propensity to form coiled-coil structures have been implicated in the fusion process driven by other viral envelope proteins, and HTLV-1 may thus conform to this general rule for viral fusion. (iii) Mutants with increased syncytium-forming ability define a region immediately amino-terminal to the membrane-spanning domain. Surprisingly, these mutants exhibited severe defects in infectivity, despite competence for fusion. Existence of this phenotype indicates that capacity for cell-to-cell fusion is not sufficient to ensure viral entry, even in cell-to-cell transmission. The ectodomain of the TM glycoprotein thus may be involved in postfusion events required for full infectivity of HTLV-1, which perhaps represents a unique feature of this poorly infectious retrovirus.",,"['Rosenberg, A R', 'Delamarre, L', 'Pique, C', 'Pham, D', 'Dokhélar, M C']",,,,
,PMC,Heterogeneous nuclear ribonucleoprotein A1 binds to the transcription-regulatory region of mouse hepatitis virus RNA,,PMC23214,,,"A cellular protein, previously described as p35/38, binds to the complementary (−)-strand of the leader RNA and intergenic (IG) sequence of mouse hepatitis virus (MHV) RNA. The extent of the binding of this protein to IG sites correlates with the efficiency of the subgenomic mRNA transcription from that IG site, suggesting that it is a requisite transcription factor. We have purified this protein and determined by partial peptide sequencing that it is heterogeneous nuclear ribonucleoprotein (hnRNP) A1, an abundant, primarily nuclear protein. hnRNP A1 shuttles between the nucleus and cytoplasm and plays a role in the regulation of alternative RNA splicing. The MHV(−)-strand leader and IG sequences conform to the consensus binding motifs of hnRNP A1. Recombinant hnRNP A1 bound to these two RNA regions in vitro in a sequence-specific manner. During MHV infection, hnRNP A1 relocalizes from the nucleus to the cytoplasm, where viral replication occurs. These data suggest that hnRNP A1 is a cellular factor that regulates the RNA-dependent RNA transcription of the virus.",,"['Li, Hsin-Pai', 'Zhang, Xuming', 'Duncan, Roger', 'Comai, Lucio', 'Lai, Michael M. C.']",,,,
,PMC,Use of synthetic antigens improves detection by enzyme-linked immunosorbent assay of antibodies against abortigenic Chlamydia psittaci in ruminants.,,PMC229957,,,"Synthetic peptide antigens were prepared for use in enzyme-linked immunosorbent assays (ELISAs) to detect serum antibodies against abortigenic strains of Chlamydia psittaci in livestock. Peptide antigens were identified with C. psittaci B577-immune sera by solid-phase scanning of overlapping octapeptides of variable domains (VDs) of the major outer membrane protein of C. psittaci serovar 1 (omp1 type C. psittaci B577). Two VD 4 regions and one VD 2 region were strongly reactive with all C. psittaci B577 antisera. Peptides encompassing these regions were synthesized with biotin and a serine-glycine-serine-glycine spacer at the N terminus and were attached to streptavidin-coated microtiter plates. In direct ELISAs with these plates, the synthetic peptides reacted with C. psittaci B577 antisera, but not with sera from specific-pathogen-free animals. Serum specimens from 40 sheep and 40 cattle, obtained from herds with abortion problems, were screened for antibodies by these C. psittaci B577 peptide ELISAs and an ELISA with recombinant, genus-specific Chlamydia lipopolysaccharide (LPS) antigen. Results from these newly developed ELISAs were compared to those from the reference C. psittaci B577 elementary body (EB) ELISA and the Chlamydia complement fixation test (CFT). The C. psittaci B577 peptide ELISAs, the LPS ELISA, and the EB ELISA correctly identified the presence or absence of antibodies against chlamydiae in all sheep and bovine sera. The Chlamydia CFT, which is the most widely accepted serodiagnostic method for chlamydial infections in animals, correctly identified the presence or absence of antibodies against chlamydiae in only 78 and 4.9% of sheep and bovine sera, respectively. These results suggest that the C. psittaci B577-peptide and Chlamydia LPS ELISAs are superior for the serodiagnosis of ruminant infections with abortigenic chlamydiae, since they are more sensitive than the CFT, they are easy to standardize, and they use readily available synthetic antigens instead of organism-derived CFT antigen.",,"['Kaltenboeck, B', 'Heard, D', 'DeGraves, F J', 'Schmeer, N']",,,,
,PMC,Primary demyelination in transgenic mice expressing interferon-γ,,PMC5321678,,,"Ever since the use of interferon-γ to treat patients with multiple sclerosis resulted in enhanced disease, the role of IFN-γ in demyelinatlon has been under question. To address this issue directly, transgenic mice were generated that expressed the cDNA of murlne IFN-γ in the central nervous system by using an oligodendrocyte-specific promoter. Expression of the transgene occurred after 8 weeks of age, at which time the murlne immune and central nervous systems are both fully developed. Directly associated with transgene expression, primary demyelination occurred and was accompanied by clinical abnormalities consistent with CNS disorders. Additionally, multiple hallmarks of immune-mediated CNS disease were observed including upregulation of MHC molecules, gliosis and lymphocytlc infiltration. These results demonstrate a direct role for IFN-γ as an Inducer of CNS demyellnatlon leading to disease and provide new opportunities for dissecting the mechanism of demyelinatlon.",,"['Horwitz, Marc S.', 'Evans, Claire F.', 'Mcgavern, Dorian B.', 'Rodriguez, Moses', 'Oldstone, Michael B.A.']",,,,
,PMC,Cough receptor sensitivity in children with acute and non-acute asthma,,PMC1758646,,,"BACKGROUND: Cough is a major symptom in some children with asthma. The relationship between cough and the severity of asthma is ill defined. A study was undertaken to test the hypotheses that, in children with asthma who cough as a major part of their asthma symptoms, cough receptor sensitivity (CRS) is heightened during an acute severe exacerbation of asthma but not in the non-acute phase and airway calibre or its change correlates with CRS. METHODS: Spirometric measurements and the capsaicin CRS test were performed on children admitted to hospital for an acute severe exacerbation of asthma. Nasal secretions were tested for viruses. The children were grouped into those who usually cough with asthma episodes and those who do not. The tests were repeated 7-10 days and 4-6 weeks later. The CRS outcome measure used was the concentration of capsaicin required to stimulate two (Cth) and five coughs (C5). RESULTS: The CRS of the group who coughed (n = 15) was significantly higher than those who did not cough (n = 16) (mean difference log Cth 0.77 mumol (95% CI 0.35 to 1.18), C5 0.72 mumol (95% CI 0.26 to 1.18)) during acute asthma but not after the exacerbation. CRS was not significantly different between groups based on the presence of a viral infection. Neither forced expiratory volume in one second (FEV1) nor its change correlated with CRS nor its change. CONCLUSIONS: In children with asthma CRS is heightened in acute severe asthma in the subgroup of children who have cough as a significant symptom with their asthma episodes. In acute and non-acute asthma CRS does not correlate with FEV1.",,"['Chang, A. B.', 'Phelan, P. D.', 'Robertson, C. F.']",,,,
,PMC,Timed appearance of lymphocytic choriomeningitis virus after gastric inoculation of mice.,,PMC1857995,,,"Arenaviruses present an emerging health threat in agrarian areas of Africa and South America; however, the natural routes of arenaviral infections are not clearly understood. Our previous studies with lymphocytic choriomeningitis virus (LCMV), the prototype arenavirus, implicate oral and intragastric routes as natural routes of infection. Our studies raised many questions about the primary site of infection and the route of dissemination after gastric infection. In this report, we use in situ hybridization to detect LCMV in various organs at different time points (0 to 96 hours). After gastric inoculation, the gastric mucosa is the initial site of viral infection, followed by infection of the spleen and liver, then ileum and last, lung, kidney, brain, and esophagus. Furthermore, our observations suggest that virus is disseminated lymphatically rather than by a hematogenous route. Infectious center assays using mononuclear cells from stomach, blood, and spleen of mice infected by the gastric route confirmed active infection with LCMV and the presence of mononuclear cells producing infectious virus in these tissues. This is the first identification of gastric epithelia as a primary site of virus infection.",,"['Rai, S. K.', 'Micales, B. K.', 'Wu, M. S.', 'Cheung, D. S.', 'Pugh, T. D.', 'Lyons, G. E.', 'Salvato, M. S.']",,,,
,PMC,Detection of group B rotaviruses in fecal samples from diarrheic calves and adult cows and characterization of their VP7 genes.,,PMC229912,,,"Groups A, B, and C rotaviruses have been identified in cattle. Group B rotaviruses are associated with sporadic cases of diarrhea in calves and adult cows. From diagnostic submissions to our laboratory, 90 fecal samples from cases of calf diarrhea, 81 fecal samples from cases of adult cow diarrhea (winter dysentery), and 20 fecal samples from case control normal adult cows were tested for group B rotaviruses by polyacrylamide gel electrophoresis (PAGE), and reverse transcription (RT)-PCR (targeting 279 bp of the VP7 gene). In addition, 53 fecal samples from diarrheic adult cows were tested for group B rotaviruses by immune electron microscopy (IEM). By RT-PCR, five samples from calves were group B rotavirus positive (5.6%). Fifteen samples from adult cows with diarrhea were group B rotavirus positive (18.5%), and none of the control fecal samples from normal cows were positive for group B rotaviruses. By PAGE, one calf sample (RT-PCR positive) was group B rotavirus positive (short electropherotype), but none of the adult cow samples were positive for group B rotaviruses. By IEM, 5 (9.4%) of the 53 fecal samples from diarrheic adult cows were group B positive (all were also RT-PCR positive). The VP7 genes of three strains (WD653 from an adult cow and the ATI and Mebus calf strains) were sequenced. The VP7 genes from the three bovine strains showed high (over 90%) nucleotide and deduced amino acid homologies, but lower homologies (48 to 61%) were seen between these genes and the genes from rodent (IDIR) and human (ADRV) group B rotaviruses. Although there were some differences of degree, all inoculated gnotobiotic calves (n = 6) showed abnormal feces between 1 and 3 days after inoculation with each of three strains of group B bovine rotaviruses, and group B rotaviruse, were detected in the feces for up to 2 weeks by RT-PCR but for shorter periods by PAGE or IEM.",,"['Chang, K O', 'Parwani, A V', 'Smith, D', 'Saif, L J']",,,,
,PMC,Transcriptional strategy of closteroviruses: mapping the 5' termini of the citrus tristeza virus subgenomic RNAs.,,PMC191890,,,"Citrus tristeza virus (CTV) induces formation of a nested set of at least nine 3' coterminal subgenomic RNAs (sgRNAs) in infected tissue. The organization and expression of the 19,296-nucleotide (nt) CTV genome resembles that of coronaviruses, with polyprotein processing, translational frameshifting, and multiple sgRNA formation, but phylogenetically the CTV polymerase, like polymerases of other closteroviruses, belongs to the Sindbis virus-like lineage of RNA virus polymerases. Both positive-strand RNA virus supergroups, coronaviruses and Sindbis-like viruses, utilize different mechanisms of transcription. To address the mechanism of CTV transcription, 5' termini for the two most abundant sgRNAs, 1.5 and 0.9 kb, respectively, were mapped by runoff reverse transcription. The two sgRNAs were demonstrated to have 48- and 38-nt 5' untranslated regions (5'-UTRs), respectively. The 5'-UTR for the 1.5-kb RNA was cloned, sequenced, and demonstrated to be colinear with the 48-nt genomic sequence upstream of the initiator codon of the respective open reading frame 10, i.e., to be of continuous template origin. The data obtained suggest that the sgRNA transcription of CTV is dissimilar from the coronavirus transcription and consistent with the transcriptional mechanism of other Sindbis-like viruses. Thus, the Sindbis virus-like mechanism of transcription of the positive-strand RNA genomes might be successfully utilized by the closterovirus genome of up to 19.3 kb with multiple sgRNAs.",,"['Karasev, A V', 'Hilf, M E', 'Garnsey, S M', 'Dawson, W O']",,,,
,PMC,Generation of coronavirus spike deletion variants by high-frequency recombination at regions of predicted RNA secondary structure.,,PMC191880,,,"Coronavirus RNA evolves in the central nervous systems (CNS) of mice during persistent infection. This evolution can be monitored by detection of a viral quasispecies of spike deletion variants (SDVs) (C. L. Rowe, S. C. Baker, M. J. Nathan, and J. O. Fleming, J. Virol. 71:2959-2969, 1997). We and others have found that the deletions cluster in the region from 1,200 to 1,800 nucleotides from the 5' end of the spike gene sequence, termed the ""hypervariable"" region. To address how SDVs might arise, we generated the predicted folding structures of the positive- and negative-strand senses of the entire 4,139-nt spike RNA sequence. We found that a prominent, isolated stem-loop structure is coincident with the hypervariable region in each structure. To determine if this predicted stem-loop is a ""hot spot"" for RNA recombination, we assessed whether this region of the spike is more frequently deleted than three other selected regions of the spike sequence in a population of viral sequences isolated from the CNS of acutely and persistently infected mice. Using differential colony hybridization of cloned spike reverse transcription-PCR products, we detected SDVs in which the hot spot was deleted but did not detect SDVs in which other regions of the spike sequence were exclusively deleted. Furthermore, sequence analysis and mapping of the crossover sites of 25 distinct patterns of SDVs showed that the majority of crossover sites clustered to two regions at the base of the isolated stem-loop, which we designated as high-frequency recombination sites 1 and 2. Interestingly, the majority of the left and right crossover sites of the SDVs were directly across from or proximal to one another, suggesting that these SDVs are likely generated by intramolecular recombination. Overall, our results are consistent with there being an important role for the spike RNA secondary structure as a contributing factor in the generation of SDVs during persistent infection.",,"['Rowe, C L', 'Fleming, J O', 'Nathan, M J', 'Sgro, J Y', 'Palmenberg, A C', 'Baker, S C']",,,,
,PMC,Specific infection and destruction of dopaminergic neurons in the substantia nigra by Theiler's virus.,,PMC191879,,,"Theiler's murine encephalomyelitis virus was stereotaxically inoculated unilaterally into the substantia nigra of the mouse brain. Virus specifically infected tyrosine hydroxylase-positive neurons and spread rostrocaudally throughout this subpopulation of neurons, resulting in impaired function and degeneration of the substantia nigra. The spread of the virus to other areas of the brain was minimal and rare.",,"['Oliver, K R', 'Brennan, P', 'Fazakerley, J K']",,,,
,PMC,Posttranslational processing and identification of a neutralization domain of the GP4 protein encoded by ORF4 of Lelystad virus.,,PMC191865,,,"GP4 is a minor structural glycoprotein encoded by ORF4 of Lelystad virus (LV). When it was immunoprecipitated from cell lysates and extracellular virus of CL2621 cells infected with LV, it was shown to have an apparent molecular mass of approximately 28 and 31 kDa, respectively. This difference in size occurred because its core N-glycans were modified to complex type N-glycans during the transport of the protein through the endoplasmic reticulum and Golgi compartment. A panel of 15 neutralizing monoclonal antibodies (MAbs) reacted with the native GP4 protein expressed by LV and the recombinant GP4 protein expressed in a Semliki Forest virus expression system. However, these MAbs did not react with the GP4 protein of U.S. isolate VR2332. To map the binding site of the MAbs, chimeric constructs composed of ORF4 of LV and VR2332 were generated. The reactivity of these constructs indicated that all the MAbs were directed against a region spanning amino acids 40 to 79 of the GP4 protein of LV. Six MAbs reacted with solid-phase synthetic dodecapeptides. The core of this site consists of amino acids 59 to 67 (SAAQEKISF). Comparison of the amino acid sequences of GP4 proteins from various European and North American isolates indicated that the neutralization domain spanning amino acids 40 to 79 is the most variable region of GP4. The neutralization domain of GP4, described here, is the first identified for LV.",,"['Meulenberg, J J', 'van Nieuwstadt, A P', 'van Essen-Zandbergen, A', 'Langeveld, J P']",,,,
,PMC,Decreased serum apolipoprotein A-I concentrations in cows infected with Salmonella typhimurium.,,PMC1189401,,,"Serum apolipoprotein A-I concentrations in cows infected with Salmonella Typhimurium were evaluated to assess its relevance in salmonellosis. Apolipoprotein A-I has been shown in rats to be secreted by the intestine as well as the liver. Clinical symptoms such as diarrhea revealed an outbreak of salmonellosis in 22 cows on a farm, and sera were obtained at 6 (acute phase), 16, 28 (convalescent period) and 42 d (postconvalescent period) after the outbreak. Apolipoprotein A-I concentrations (mean +/- SD, mg/mL), determined by ELISA, were 0.598 +/- 0.497 (day 6), 0.111 +/- 0.060 (day 16), 0.432 +/- 0.311 (day 28) and 0.727 +/- 0.516 (day 42). Compared with the concentration at day 42, those at 16 and 28 d were significantly (P < 0.01, P < 0.05) lower, but that at day 6 was not. The serum concentration of apolipoprotein B-100 (of liver origin in cattle) was unaltered during the course of salmonellosis. The concentration of apolipoprotein A-I was positively correlated with those of serum total cholesterol (r = 0.589, P < 0.01) and phospholipids (r = 0.590, P < 0.01). These results suggest that apolipoprotein A-I in cattle is in part of intestinal origin, and also that its decreased serum concentration in salmonellosis can be attributed to the reduced intestinal synthesis or secretion of this apolipoprotein. Moreover, as a potential carrier for dietary lipids such as cholesterol, determination of serum apolipoprotein A-I concentration is suggested to be useful when assessing the nutritional status of the affected cows.",,"['Oikawa, S', 'Katoh, N', 'Itoh, H', 'Miyamoto, T', 'Konno, M', 'Kajita, T']",,,,
,PMC,Development of PCR-based techniques to identify porcine transmissible gastroenteritis coronavirus isolates.,,PMC1189399,,,"Sixteen isolates of transmissible gastroenteritis virus and one isolate of porcine respiratory coronavirus were characterized using RT-PCR amplification of 4 antigenic subsites in the site A epitope on the TGEV spike gene. The PCR products were digested with restriction enzymes Sau3AI and SspI and the sizes of the fragments were determined. Three different digestion patterns were observed with each enzyme. The recognition site for Sau3AI was missing in 1 isolate, was present in 13 isolates and 3 isolates had 2 sites. PCR-products with a single site had 3 different fragment sizes and the other isolates produced 2 fragments with different sizes. The SspI recognition site was not present in 5 isolates and 12 isolates had a single site that produced 2 fragments of different sizes. Based on the restriction fragment sizes, the 17 isolates were separated into 7 groups. Direct sequencing of the 455 bp nested set fragments demonstrated greater than 96% sequence homology among the 16 isolates and 100% homology in the 4 antigenic subsites in the conserved site A epitope. The groups are discussed in relation to their sequence homology and virulence. In vitro procedures have been developed to identify several porcine enteric coronavirus isolates at the strain level.",,"Woods, R D",,,,
,PMC,Formation of plant RNA virus replication complexes on membranes: role of an endoplasmic reticulum-targeted viral protein.,http://dx.doi.org/10.1093/emboj/16.13.4049,PMC1170028,,,"The mechanisms that direct positive-stranded RNA virus replication complexes to plant and animal cellular membranes are poorly understood. We describe a specific interaction between a replication protein of an RNA plant virus and membranes in vitro and in live cells. The tobacco etch virus (TEV) 6 kDa protein associated with membranes as an integral protein via a central 19 amino acid hydrophobic domain. In the presence or absence of other viral proteins, fluorescent fusion proteins containing the 6 kDa protein associated with large vesicular compartments derived from the endoplasmic reticulum (ER). Infection by TEV was associated with a collapse of the ER network into a series of discrete aggregated structures. Viral RNA replication complexes from infected cells were also associated with ER-like membranes. Targeting of TEV RNA replication complexes to membranous sites of replication is proposed to involve post-translational interactions between the 6 kDa protein and the ER.",,"['Schaad, M C', 'Jensen, P E', 'Carrington, J C']",,,,
,PMC,Respiratory syncytial virus infection results in airway hyperresponsiveness and enhanced airway sensitization to allergen.,,PMC508183,,,"Viral respiratory infections can predispose to the development of asthma by mechanisms that are presently undetermined. Using a murine model of respiratory syncytial virus (RSV) infection, acute infection is associated with airway hyperresponsiveness as well as enhanced responses to subsequent sensitization to allergen. We demonstrate that acute viral infection results in increased airway responsiveness to inhaled methacholine and pulmonary neutrophilic and eosinophilic inflammation. This response is associated with predominant production of Th-1-type cytokines in peribronchial lymph node cells in vitro. Mice sensitized to ovalbumin via the airways after RSV infection developed increased airway responsiveness to methacholine and pulmonary eosinophilic and neutrophilic inflammation, associated with the predominant production of Th-2-type cytokines. Treatment of the mice with anti-IL-5 antibody abolished airway hyperresponsiveness and eosinophilic but not neutrophilic inflammation in both acutely infected mice and mice sensitized after infection. We conclude that RSV infection results in airway hyperresponsiveness in the acute phase and leads to changes in immune function that can enhance the effects of airway sensitization to antigen after infection. In both situations, airway hyperresponsiveness is closely associated with pulmonary eosinophilic inflammation. This model provides a means for further analyzing the influence of viral respiratory infections on airway sensitization and the development of altered airway responsiveness.",,"['Schwarze, J', 'Hamelmann, E', 'Bradley, K L', 'Takeda, K', 'Gelfand, E W']",,,,
,PMC,Detection of rhinovirus in sinus brushings of patients with acute community-acquired sinusitis by reverse transcription-PCR.,,PMC229843,,,"Of 20 adults with acute community-acquired sinusitis (ACAS), rhinovirus was detected in specimens from 10 (50%) patients, including maxillary aspirates from 8 (40%) patients and nasal swabs from 9 (45%) patients, by reverse transcription-PCR (RT-PCR). Human coronavirus was detected by RT-PCR in nasal swabs from 3 of 20 patients but in no sinus secretions. These findings suggest that rhinovirus is an important cause of ACAS and that viral invasion of the sinus cavity itself may be a common event during the disease.",,"['Pitkäranta, A', 'Arruda, E', 'Malmberg, H', 'Hayden, F G']",,,,
,PMC,A subgenomic mRNA transcript of the coronavirus mouse hepatitis virus strain A59 defective interfering (DI) RNA is packaged when it contains the DI packaging signal.,,PMC191817,,,"In infected cells, only the genomic RNA of the coronavirus mouse hepatitis virus strain A59 (MHV-A59) is packaged into the virions. In this study, we show that a subgenomic (sg) defective interfering (DI) RNA can be packaged into virions when it contains the DI RNA packaging signal (DI RNA-Ps). However, the sg DI RNA is packaged less efficiently than the DI genomic RNA. Thus, while specificity of packaging of RNAs into MHV-A59 virions is determined by the DI RNA-Ps, efficiency of packaging is determined by additional factors.",,"['Bos, E C', 'Dobbe, J C', 'Luytjes, W', 'Spaan, W J']",,,,
,PMC,Identification of an ATPase activity associated with a 71-kilodalton polypeptide encoded in gene 1 of the human coronavirus 229E.,,PMC191807,,,"Human coronavirus 229E gene expression involves proteolytic processing of the gene 1-encoded polyproteins pp1a and pp1ab. In this study, we have detected a 71-kDa polypeptide in virus-infected cells that is released from pp1ab by the virus-encoded 3C-like proteinase and that has been predicted to contain both metal-binding and helicase domains. The polypeptide encompasses amino acids Ala-4996 to Gln-5592 of pp1ab and exhibits nucleic acid-stimulated ATPase activity when expressed as a fusion protein with the Escherichia coli maltose-binding protein. These data provide the first identification of a coronavirus open reading frame 1b-encoded enzymatic activity.",,"['Heusipp, G', 'Harms, U', 'Siddell, S G', 'Ziebuhr, J']",,,,
,PMC,"Hemagglutinin-esterase, a novel structural protein of torovirus.",,PMC191764,,,"We have characterized the 3'-most 3 kb of the genome of bovine torovirus (BoTV) strain Breda. A novel 1.2-kb gene, located between the genes for the membrane and nucleocapsid proteins, was identified. This gene, the 3'-most 0.5 kb of which is also present in the genome of the equine torovirus isolate Berne virus (BEV), codes for a class I membrane protein displaying 30% sequence identity with the hemagglutinin-esterases (HEs) of coronaviruses and influenza C viruses. Heterologous expression of the BoTV HE gene yielded a 65,000-molecular weight N-glycosylated protein displaying acetylesterase activity. Serologic evidence indicates that the HE homolog is expressed during the natural infection and represents a prominent antigen. By using an antiserum raised against residues 13 to 130 of HE, the HE protein was detected in radioiodinated, sucrose gradient-purified BoTV preparations. Formal evidence that HE is a structural protein was provided by immunoelectron microscopy. In addition to the large, 17- to 20-nm spikes, BoTV virions possess shorter surface projections (6 nm on average). We postulate that these surface projections, which are absent from the BEV virion, are composed of the BoTV HE homolog. The HE gene, which has now been demonstrated in three different virus genera, is a showpiece example of modular evolution.",,"['Cornelissen, L A', 'Wierda, C M', 'van der Meer, F J', 'Herrewegh, A A', 'Horzinek, M C', 'Egberink, H F', 'de Groot, R J']",,,,
,PMC,Interference of coronavirus infection by expression of immunoglobulin G (IgG) or IgA virus-neutralizing antibodies.,,PMC191761,,,"Immunoglobulin gene fragments encoding the variable modules of the heavy and light chains of a transmissible gastroenteritis coronavirus (TGEV)-neutralizing monoclonal antibody (MAb) have been cloned and sequenced. The selected MAb recognizes a highly conserved viral epitope and does not lead to the selection of neutralization escape mutants. The sequences of MAb 6A.C3 kappa and gamma 1 modules were identified as subgroup V and subgroup IIIC, respectively. The chimeric immunoglobulin genes encoding the variable modules from the murine MAb and constant modules of human gamma 1 and kappa chains were constructed by reverse transcriptase PCR. Chimeric immunoglobulins were stably or transiently expressed in murine myelomas or COS cells, respectively. The secreted recombinant antibodies had radioimmunoassay titers (i.e., the highest dilution giving a threefold increase over the background) higher than 10(3) and reduced the infectious virus more than 10(4)-fold. Recombinant dimeric immunoglobulin A (IgA) showed a 50-fold enhanced neutralization of TGEV relative to a recombinant monomeric IgG1 which contained the identical antigen binding site. Stably transformed epithelial cell lines which expressed either recombinant IgG or IgA TGEV-neutralizing antibodies reduced virus production by > 10(5)-fold after infection with homologous virus, although a residual level of virus production (< 10(2) PFU/ml) remained in less than 0.1% of the cells. This low-level persistent infection was shown not to be due to the selection of neutralization escape mutants. The implications of these findings for somatic gene therapy with recombinant antibodies are discussed.",,"['Castilla, J', 'Sola, I', 'Enjuanes, L']",,,,
,PMC,Specific cytotoxic T lymphocytes are involved in in vivo clearance of infectious bronchitis virus.,,PMC191752,,,"Cytotoxic T-lymphocyte (CTL) responses to infectious bronchitis virus (IBV) were determined at regular intervals between 3 and 30 days postinfection (p.i.). The maximum response with 82% lysis of labeled target cells was detected at 10 days p.i. The specific CTL response did not begin to decline until the amount of virus, which peaked at day 8 p.i. in both the kidneys and lungs, started to decrease. Clinical respiratory signs of illness also correlated with amount of virus. CTL activity was shown to be major histocompatibility complex (MHC) class restricted because the lysis of MHC-mismatched targets was negligible, and lysis was mediated by CD8+ CD4- T cells, as the CTL response could be abolished with removal of CD8+ CD4- but not CD4+ CD8- lymphocytes. In contrast, immunoglobulin M (IgM) antibody was not detected until day 10 p.i., and levels peaked at day 12 p.i.; IgG antibody levels were minimal until day 15 p.i. but continued to increase exponentially until day 30 p.i., the last day examined. In summary, CTL responses correlated with initial decreases in infection and illness.",,"['Seo, S H', 'Collisson, E W']",,,,
,PMC,Analysis of a recombinant mouse hepatitis virus expressing a foreign gene reveals a novel aspect of coronavirus transcription.,,PMC191750,,,"We have inserted heterologous genetic material into the nonessential gene 4 of the coronavirus mouse hepatitis virus (MHV) in order to test the applicability of targeted RNA recombination for site-directed mutagenesis of the MHV genome upstream of the nucleocapsid (N) gene and to develop further genetic tools for site-directed mutagenesis of structural genes other than N. Initially, a 19-nucleotide tag was inserted into the start of gene 4a of MHV strain A59 with the N gene deletion mutant Alb4 as the recipient virus. In further work, the entire gene for the green fluorescent protein (GFP) was inserted in place of gene 4, creating the currently largest known RNA virus. The expression of GFP was demonstrated by Western blot analysis of infected cell lysates; however, the level of GFP expression was not sufficient to allow detection of fluorescence of viral plaques. Northern blot analysis of transcripts of GFP recombinants showed the expected alteration of the pattern of the nested MHV subgenomic mRNAs. Surprisingly, though, GFP recombinants also produced an RNA species that was the same size as wild-type mRNA4. Analysis of the 5' end of this species revealed that it was actually a collection of mRNAs originating from 10 different genomic fusion sites, none possessing a canonical intergenic sequence. The finding of these aberrant mRNAs suggests that long-range RNA or the ribonucleoprotein structure of the MHV genome can sometimes be the sole determinant of the site of initiation of transcription.",,"['Fischer, F', 'Stegen, C F', 'Koetzner, C A', 'Masters, P S']",,,,
,PMC,A novel a-factor-related peptide of Saccharomyces cerevisiae that exits the cell by a Ste6p-independent mechanism.,,PMC276152,,,"Many secreted signaling molecules are synthesized as precursors that undergo multiple maturation steps to generate their mature forms. The Saccharomyces cerevisiae mating pheromone a-factor is a C-terminally isoprenylated and carboxylmethylated dodecapeptide that is initially synthesized as a larger precursor containing 36 or 38 amino acids. We have previously shown that the maturation of a-factor occurs by an ordered biogenesis pathway involving 1) three C-terminal modification steps, 2) two N-terminal proteolytic processing events, and 3) a nonclassical export mechanism mediated by the ATP-binding-cassette (ABC) transporter Ste6p. In the present study, we demonstrate that an unexpected and abundant a-factor-related peptide (AFRP) exists in the culture fluid of MATa cells and that its biogenesis is integrally related to that of mature a-factor itself. We show by purification followed by mass spectrometry that AFRP corresponds to the C-terminal 7 amino acids (VFWDPAC) of mature a-factor (YIIKGVFWDPAC), including both the farnesyl- and carboxylmethylcysteine modifications. The formation and export of AFRP displays three striking features. First, we show that AFRP is produced intracellularly and that mutants (ste24 and axl1) that cannot produce mature a-factor due to an N-terminal processing defect are nevertheless normal for AFRP production. Thus, AFRP is not derived from mature a-factor but, instead, from the P1 form of the a-factor precursor. Second, fusion constructs with foreign amino acids substituted for authentic a-factor residues still yield AFRP-sized molecules; however, the composition of these corresponds to the altered residues instead of to AFRP residues. Thus, AFRP may be generated by a sequence-dependent but length-specific proteolytic activity. Third, a-factor and AFRP use distinct cellular machinery for their secretion. Whereas a-factor export is Ste6p-dependent, AFRP is secreted normally even in a ste6 deletion mutant. Thus, AFRP may exit the cell by another ATP-binding-cassette transporter, a different type of transporter altogether, or possibly by diffusion. Taken together, these studies indicate that the biogenesis of AFRP involves novel mechanisms and machinery, distinct from those used to generate mature a-factor. Because AFRP neither stimulates nor inhibits mating or a-factor halo activity, its function remains an intriguing question.",,"['Chen, P', 'Choi, J D', 'Wang, R', 'Cotter, R J', 'Michaelis, S']",,,,
,PMC,QUIZ CORNER,,PMC1576896,,,,,,,,,
,PMC,Dissemination of Chlamydia trachomatis chronic genital tract infection in gamma interferon gene knockout mice.,,PMC175296,,,"Mice (C57BL/6), treated with progesterone and infected intravaginally with the mouse pneumonitis strain of Chlamydia trachomatis (MoPn), acquired genital tract disease that ascended from the endocervix to the uterine horns, oviducts, and ovaries in a temporal fashion before the occurrence of spontaneous microbiological resolution by about 28 days after infection. Surprisingly, dissemination of MoPn in small numbers to draining lymph nodes, the peritoneal cavity, spleen, liver, kidneys, and lungs occurred in normal mice during the early stages of disease (7 to 14 days) in a portion of infected animals but resolved from these tissues, by microbiological criteria, prior to resolution of genital tract involvement. In contrast, gamma interferon knockout (IFN-gamma KO) mice exhibited dissemination of infection to a greater extent and for longer periods in a variety of tissues, and a portion of infected IFN-gamma KO mice failed to microbiologically resolve their genital tract disease. By comparison, C57BL/6 SCID mice uniformly failed to resolve their genital tract disease and exhibited high levels of dissemination to all tissues tested for extended (50-day) periods of times. Interestingly, although IFN-gamma KO mice failed to completely clear organisms from their genital tracts, they exhibited an attenuated infection indistinguishable from that of heterozygous littermates when challenged 112 days after primary infection. These data support a role for IFN-gamma in containing dissemination of MoPn from the genital tract to extragenital sites and in the microbiological resolution of infection. Data also indicate that IFN-gamma is not required for modulating reinfections, which normally follow a shorter and less dramatic course.",,"['Cotter, T W', 'Ramsey, K H', 'Miranpuri, G S', 'Poulsen, C E', 'Byrne, G I']",,,,
,PMC,A retention signal necessary and sufficient for Golgi localization maps to the cytoplasmic tail of a Bunyaviridae (Uukuniemi virus) membrane glycoprotein.,,PMC191693,,,"Members of the Bunyaviridae family mature by a budding process in the Golgi complex. The site of maturation is thought to be largely determined by the accumulation of the two spike glycoproteins, G1 and G2, in this organelle. Here we show that the signal for localizing the Uukuniemi virus (a phlebovirus) spike protein complex to the Golgi complex resides in the cytoplasmic tail of G1. We constructed chimeric proteins in which the ectodomain, transmembrane domain (TMD), and cytoplasmic tail (CT) of Uukuniemi virus G1 were exchanged with the corresponding domains of either vesicular stomatitis virus G protein (VSV G), chicken lysozyme, or CD4, all proteins readily transported to the plasma membrane. The chimeras were expressed in HeLa or BHK-21 cells by using either the T7 RNA polymerase-driven vaccinia virus system or the Semliki Forest virus system. The fate of the chimeric proteins was monitored by indirect immunofluorescence, and their localizations were compared by double labeling with markers specific for the Golgi complex. The results showed that the ectodomain and TMD (including the 10 flanking residues on either side of the membrane) of G1 played no apparent role in targeting chimeric proteins to the Golgi complex. Instead, all chimeras containing the CT of G1 were efficiently targeted to the Golgi complex and colocalized with mannosidase II, a Golgi-specific enzyme. Conversely, replacing the CT of G1 with that from VSV G resulted in the efficient transport of the chimeric protein to the cell surface. Progressive deletions of the G1 tail suggested that the Golgi retention signal maps to a region encompassing approximately residues 10 to 50, counting from the proposed border between the TMD and the tail. Both G1 and G2 were found to be acylated, as shown by incorporation of [3H]palmitate into the viral proteins. By mutational analyses of CD4-G1 chimeras, the sites for palmitylation were mapped to two closely spaced cysteine residues in the G1 tail. Changing either or both of these cysteines to alanine had no effect on the targeting of the chimeric protein to the Golgi complex.",,"['Andersson, A M', 'Melin, L', 'Bean, A', 'Pettersson, R F']",,,,
,PMC,The amphotropic murine leukemia virus receptor gene encodes a 71-kilodalton protein that is induced by phosphate depletion.,,PMC191678,,,"The amphotropic murine leukemia virus (MuLV) can infect cells from a number of mammals, including humans, via its specific receptor. Basic knowledge of amphotropic MuLV receptor expression is likely to be useful in the development and improvement of gene therapy protocols based on amphotropic-pseudotyped vectors. To investigate the expression of the human receptor for the amphotropic MuLV (GLVR-2, newly termed Pit2), we determined its mRNA levels in several cell lines and found them to vary significantly. Induction of increased levels of mRNA after removal of phosphate from the media was observed in two osteosarcoma cell lines. The increase in GLVR-2 mRNA resulted in a concomitant rise in the levels of a 71-kDa protein specifically recognized by affinity-purified antibodies against GLVR-2. Using these antibodies, we were able to confirm the intracellular topology of the large hydrophilic domain between the proposed sixth and seventh transmembrane domains of the GLVR-2 protein. This assignment is in agreement with the fourth extracellular loop being outside the cell, consistent with the proposal that the fourth extracellular loop of GLVR-2 contains the envelope binding site.",,"['Chien, M L', 'Foster, J L', 'Douglas, J L', 'Garcia, J V']",,,,
,PMC,Sequence and overexpression of GPP130/GIMPc: evidence for saturable pH-sensitive targeting of a type II early Golgi membrane protein.,,PMC305715,,,"It is thought that residents of the Golgi stack are localized by a retention mechanism that prevents their forward progress. Nevertheless, some early Golgi proteins acquire late Golgi modifications. Herein, we describe GPP130 (Golgi phosphoprotein of 130 kDa), a 130-kDa phosphorylated and glycosylated integral membrane protein localized to the cis/medial Golgi. GPP130 appears to be the human counterpart of rat Golgi integral membrane protein, cis (GIMPc), a previously identified early Golgi antigen that acquires late Golgi carbohydrate modifications. The sequence of cDNAs encoding GPP130 indicate that it is a type II membrane protein with a predicted molecular weight of 81,880 and an unusually acidic lumenal domain. On the basis of the alignment with several rod-shaped proteins and the presence of multiple predicted coiled-coil regions, GPP130 may form a flexible rod in the Golgi lumen. In contrast to the behavior of previously studied type II Golgi proteins, overexpression of GPP130 led to a pronounced accumulation in endocytotic vesicles, and endogenous GPP130 reversibly redistributed to endocytotic vesicles after chloroquine treatment. Thus, localization of GPP130 to the early Golgi involves steps that are saturable and sensitive to lumenal pH, and GPP130 contains targeting information that specifies its return to the Golgi after chloroquine washout. Given that GIMPc acquires late Golgi modifications in untreated cells, it seems likely that GPP130/GIMPc continuously cycles between the early Golgi and distal compartments and that an unidentified retrieval mechanism is important for its targeting.",,"['Linstedt, A D', 'Mehta, A', 'Suhan, J', 'Reggio, H', 'Hauri, H P']",,,,
,PMC,"Biosynthesis, purification, and characterization of the human coronavirus 229E 3C-like proteinase.",,PMC191551,,,"Coronavirus gene expression involves proteolytic processing of the gene 1-encoded polyprotein(s), and a key enzyme in this process is the viral 3C-like proteinase. In this report, we describe the biosynthesis of the human coronavirus 229E 3C-like proteinase in Escherichia coli and the enzymatic properties, inhibitor profile, and substrate specificity of the purified protein. Furthermore, we have introduced single amino acid substitutions and carboxyl-terminal deletions into the recombinant protein and determined the ability of these mutant 3C-like proteinases to catalyze the cleavage of a peptide substrate. Using this approach, we have identified the residues Cys-3109 and His-3006 as being indispensable for catalytic activity. Our results also support the involvement of His-3127 in substrate recognition, and they confirm the requirement of the carboxyl-terminal extension found in coronavirus 3C-like proteinases for enzymatic activity. These data provide experimental evidence for the relationship of coronavirus 3C-like proteinases to other viral chymotrypsin-like enzymes, but they also show that the coronavirus proteinase has additional, unique properties.",,"['Ziebuhr, J', 'Heusipp, G', 'Siddell, S G']",,,,
,PMC,Assembled coronavirus from complementation of two defective interfering RNAs.,,PMC191544,,,"In the presence of an RNA- temperature-sensitive (ts) mutant helper virus, two coronavirus mouse hepatitis virus (MHV) defective interfering (DI) RNAs complemented each other, resulting in the assembly of MHV particles; we used this ability to complement as a means to study coronavirus assembly. One of the two DI RNAs was DIssA, a naturally occurring self-replicating DI RNA encoding N protein and the gene 1 proteins that encode RNA polymerase function; DIssA supports the replication and transcription of other non-self-replicating DI RNAs. The other DI was a genetically engineered DI RNA that encoded sM and M proteins. Coinfection of these two DIs at the nonpermissive temperature for the ts helper virus resulted in replication and transcription of both DI RNAs but not in synthesis of the helper virus RNAs. MHV particles containing DI RNAs, N protein, and M protein, all of which were exclusively derived from the two DI RNAs, were released from the coinfected cells; the amount of sM protein was below the limits of detection. Analyses of DI RNAs with mutations in the two envelope protein genes demonstrated that M and sM proteins appeared to be required for assembly and release of MHV particles that contained DI RNAs and N protein, while S protein was not required for assembly and release of MHV particles.",,"['Kim, K H', 'Narayanan, K', 'Makino, S']",,,,
,PMC,"RNA-protein interactions: involvement of NS3, NS5, and 3' noncoding regions of Japanese encephalitis virus genomic RNA.",,PMC191493,,,"The mechanism of replication of the flavivirus Japanese encephalitis virus (JEV) is not well known. The structures at the 3' end of the viral genome are highly conserved among divergent flaviviruses, suggesting that they may function as cis-acting signals for RNA replication and, as such, might specifically bind to cellular or viral proteins. UV cross-linking experiments were performed to identify the proteins that bind with the JEV plus-strand 3' noncoding region (NCR). Two proteins, p71 and p110, from JEV-infected but not from uninfected cell extracts were shown to bind specifically to the plus-strand 3' NCR. The quantities of these binding proteins increased during the course of JEV infection and correlated with the levels of JEV RNA synthesis in cell extracts. UV cross-linking coupled with Western blot and immunoprecipitation analysis showed that the p110 and p71 proteins were JEV NS5 and NS3, respectively, which are proposed as components of the RNA replicase. The putative stem-loop structure present within the plus-strand 3' NCR was required for the binding of these proteins. Furthermore, both proteins could interact with each other and form a protein-protein complex in vivo. These findings suggest that the 3' NCR of JEV genomic RNA may form a replication complex together with NS3 and NS5; this complex may be involved in JEV minus-strand RNA synthesis.",,"['Chen, C J', 'Kuo, M D', 'Chien, L J', 'Hsu, S L', 'Wang, Y M', 'Lin, J H']",,,,
,PMC,Transmembrane domain-dependent sorting of proteins to the ER and plasma membrane in yeast.,http://dx.doi.org/10.1093/emboj/16.8.1832,PMC1169786,,,"Sorting of membrane proteins between compartments of the secretory pathway is mediated in part by their transmembrane domains (TMDs). In animal cells, TMD length is a major factor in Golgi retention. In yeast, the role of TMD signals is less clear; it has been proposed that membrane proteins travel by default to the vacuole, and are prevented from doing so by cytoplasmic signals. We have investigated the targeting of the yeast endoplasmic reticulum (ER) t-SNARE Ufe1p. We show that the amino acid sequence of the Ufe1p TMD is important for both function and ER targeting, and that the requirements for each are distinct. Targeting is independent of Rer1p, the only candidate sorting receptor for TMD sequences currently known. Lengthening the Ufe1p TMD allows transport along the secretory pathway to the vacuole or plasma membrane. The choice between these destinations is determined by the length and composition of the TMD, but not by its precise sequence. A longer TMD is required to reach the plasma membrane in yeast than in animal cells, and shorter TMDs direct proteins to the vacuole. TMD-based sorting is therefore a general feature of the yeast secretory pathway, but occurs by different mechanisms at different points.",,"['Rayner, J C', 'Pelham, H R']",,,,
,PMC,Relevance of nucleic acid amplification techniques for diagnosis of respiratory tract infections in the clinical laboratory.,,PMC172918,,,"Clinical laboratories are increasingly receiving requests to perform nucleic acid amplification tests for the detection of a wide variety of infectious agents. In this paper, the efficiency of nucleic acid amplification techniques for the diagnosis of respiratory tract infections is reviewed. In general, these techniques should be applied only for the detection of microorganisms for which available diagnostic techniques are markedly insensitive or nonexistent or when turnaround times for existing tests (e.g., viral culture) are much longer than those expected with amplification. This is the case for rhinoviruses, coronaviruses, and hantaviruses causing a pulmonary syndrome, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Coxiella burnetii. For Legionella spp. and fungi, contamination originating from the environment is a limiting factor in interpretation of results, as is the difficulty in differentiating colonization and infection. Detection of these agents in urine or blood by amplification techniques remains to be evaluated. In the clinical setting, there is no need for molecular diagnostic tests for the diagnosis of Pneumocystis carinii. At present, amplification methods for Mycobacterium tuberculosis cannot replace the classical diagnostic techniques, due to their lack of sensitivity and the absence of specific internal controls for the detection of inhibitors of the reaction. Also, the results of interlaboratory comparisons are unsatisfactory. Furthermore, isolates are needed for susceptibility studies. Additional work remains to be done on sample preparation methods, comparison between different amplification methods, and analysis of results. The techniques can be useful for the rapid identification of M. tuberculosis in particular circumstances, as well as the rapid detection of most rifampin-resistant isolates. The introduction of diagnostic amplification techniques into a clinical laboratory implies a level of proficiency for excluding false-positive and false-negative results.",,"['Ieven, M', 'Goossens, H']",,,,
,PMC,Point mutations in the S protein connect the sialic acid binding activity with the enteropathogenicity of transmissible gastroenteritis coronavirus.,,PMC191465,,,"Enteropathogenic transmissible gastroenteritis virus (TGEV), a porcine coronavirus, is able to agglutinate erythrocytes because of sialic acid binding activity. Competitive inhibitors that may mask the sialic acid binding activity can be inactivated by sialidase treatment of virions. Here, we show that TGEV virions with efficient hemagglutinating activity were also obtained when cells were treated with sialidase prior to infection. This method was used to analyze TGEV mutants for hemagglutinating activity. Recently, mutants with strongly reduced enteropathogenicity that have point mutations or a deletion of four amino acids within residues 145 to 155 of the S protein have been described. Here, we show that in addition to their reduced pathogenicity, these mutants also have lost hemagglutinating activity. These results connect sialic acid binding activity with the enteropathogenicity of TGEV.",,"['Krempl, C', 'Schultze, B', 'Laude, H', 'Herrler, G']",,,,
,PMC,Inducible nitric oxide synthase in Theiler's murine encephalomyelitis virus infection.,,PMC191455,,,"We investigated the role of inducible nitric oxide synthase (iNOS) in Theiler's murine encephalomyelitis virus (TMEV) infection of susceptible (SJL) and resistant (C57BL/6 [B6]) strains of mice. TMEV is an excellent model of virus-induced demyelinating disease, such as multiple sclerosis (MS). Previous studies of others have suggested that NO may play a role in the pathogenesis of demyelinating disease. The presence and level of iNOS were determined in the brains and spinal cords of SJL and B6 TMEV-infected mice by the following methods: (i) PCR amplification of iNOS transcripts, followed by Southern blotting with an iNOS-specific probe, and (ii) immunohistochemical staining with an anti-iNOS-specific affinity-purified rabbit antibody. iNOS-specific transcripts were determined in the brains and spinal cord of both SJL and B6 TMEV-infected mice on days 0 (control), days 3, 6, and 10 (encephalitic stage of disease), and days 39 to 42, 66, and 180 (demyelinating phase) postinfection (p.i.). iNOS-specific transcripts were found in the brains and spinal cords of both SJL and B6 TMEV-infected mice at 6, 10, and 39 (SJL) days p.i., but they were absent in mock-infected mice and in TMEV-infected SJL and B6 mice at 0, 3, 66, and 180 days p.i. Immunohistochemical staining confirmed the presence of iNOS protein in both TMEV-infected SJL and B6 mice at days 6 and 10 p.i., but not at days 0, 3, 66, and 180 days p.i. Weak iNOS staining was also observed in TMEV-infected SJL mice at 42 days p.i. iNOS-positive staining was found in reactive astrocytes surrounding areas of necrotizing inflammation, particularly in the midbrain. Weak iNOS staining was also observed in cells of the monocyte/macrophage lineage in areas of parenchymal inflammation and necrosis (mesencephalon) and in leptomeningeal and white matter perivascular infiltrates of the spinal cord. Rod-shaped microglia-like cells and foamy macrophages (myelin-laden) were iNOS negative. These results suggest that NO does not play a direct role in the late phase of demyelinating disease in TMEV-infected mice.",,"['Oleszak, E L', 'Katsetos, C D', 'Kuzmak, J', 'Varadhachary, A']",,,,
,PMC,A role for naturally occurring variation of the murine coronavirus spike protein in stabilizing association with the cellular receptor.,,PMC191445,,,"Murine hepatitis virus (MHV), a coronavirus, initiates infection by binding to its cellular receptor (MHVR) via spike (S) proteins projecting from the virion membrane. The structures of these S proteins vary considerably among MHV strains, and this variation is generally considered to be important in determining the strain-specific pathologies of MHV infection, perhaps by affecting the interaction between MHV and the MHVR. To address the relationships between S variation and receptor binding, assays capable of measuring interactions between MHV and MHVR were developed. The assays made use of a novel soluble form of the MHVR, sMHVR-Ig, which comprised the virus-binding immunoglobulin-like domain of MHVR fused to the Fc portion of human immunoglobulin G1. sMHVR-Ig was stably expressed as a disulfide-linked dimer in human 293 EBNA cells and was immobilized to Sepharose-protein G via the Fc domain. The resulting Sepharose beads were used to adsorb radiolabelled MHV particles. At 4 degrees C, the beads specifically adsorbed two prototype MHV strains, MHV JHM (strain 4) and a tissue culture-adapted mutant of MHV JHM, the JHMX strain. A shift to 37 degrees C resulted in elution of JHM but not JHMX. This in vitro observation of JHM (but not JHMX) elution from its receptor at 37 degrees C was paralleled by a corresponding 37 degrees C elution of receptor-associated JHM (but not JHMX) from tissue culture cells. The basis for this difference in maintenance of receptor association was correlated with a large deletion mutation present within the JHMX S protein, as sMHVR-Ig exhibited relatively thermostable binding to vaccinia virus-expressed S proteins containing the deletion. These results indicate that naturally occurring mutations in the coronavirus S protein affect the stability of the initial interaction with the host cell and thus contribute to the likelihood of successful infection by incoming virions. These changes in virus entry features may result in coronaviruses with novel pathogenic properties.",,"Gallagher, T M",,,,
,PMC,Evolution of mouse hepatitis virus: detection and characterization of spike deletion variants during persistent infection.,,PMC191424,,,"High-frequency RNA recombination has been proposed as an important mechanism for generating viral deletion variants of murine coronavirus. Indeed, a number of variants with deletions in the spike glycoprotein have been isolated from persistently infected animals. However, the significance of generating and potentially accumulating deletion variants in the persisting viral RNA population is unclear. To study this issue, we evaluated the evolution of spike variants by examining the population of spike RNA sequences detected in the brains and spinal cords of mice inoculated with coronavirus and sacrificed at 4, 42, or 100 days postinoculation. We focused on the S1 hypervariable region since previous investigators had shown that this region is subject to recombination and deletion. RNA isolated from the brains or spinal cords of infected mice was rescued by reverse transcription-PCR, and the amplified products were cloned and used in differential colony hybridizations to identify individual isolates with deletions. We found that 11 of 20 persistently infected mice harbored spike deletion variants (SDVs), indicating that deletions are common but not required for persistent infection. To determine if a specific type of SDV accumulated during persistence, we sequenced 106 of the deletion isolates. We identified 23 distinct patterns of SDVs, including 5 double-deletion variants. Furthermore, we found that each mouse harbored distinct variants in its central nervous system (CNS), suggesting that SDVs are generated during viral replication in the CNS. Interestingly, mice with the most severe and persisting neurological disease harbored the most prevalent and diverse quasispecies of SDVs. Overall, these findings illustrate the complexity of the population of persisting viral RNAs which may contribute to chronic disease.",,"['Rowe, C L', 'Baker, S C', 'Nathan, M J', 'Fleming, J O']",,,,
,PMC,Coexistence in lactate dehydrogenase-elevating virus pools of variants that differ in neuropathogenicity and ability to establish a persistent infection.,,PMC191418,,,"Neuropathogenic isolates of lactate dehydrogenase-elevating virus (LDV) differ from nonneuropathogenic isolates in their unique ability to infect anterior horn neurons of immunosuppressed C58 and AKR mice and cause paralytic disease (age-dependent poliomyelitis [ADPM]). However, we and others have found that neuropathogenic LDVs fail to retain their neuropathogenicity during persistent infections of both ADPM-susceptible and nonsusceptible mice. On the basis of a segment in open reading frame 2 that differs about 60% between the neuropathogenic LDV-C and the nonneuropathogenic LDV-P, we have developed a reverse transcription-PCR assay that distinguishes between the genomes of the two LDVs and detects as little as 10 50% infectious doses (ID50) of LDV. With this assay, we found that LDV-P and LDV-C coexist in most available pools of LDV-C and LDV-P. For example, various plasma pools of 10(9.5) ID50 of LDV-C/ml contained about 10(5) ID50 of LDV-P/ml. Injection of such an LDV-C pool into mice of various strains resulted in the rapid displacement in the circulation of LDV-C by LDV-P as the predominant LDV, but LDV-C also persisted in the mice at a low level along with LDV-P. We have freed LDV-C of LDV-P by endpoint dilution (LDV-C-EPD). LDV-C-EPD infected mice as efficiently as did LDV-P, but its level of viremia during the persistent phase was only 1/10,000 that observed for LDV-P. LDV-permissive macrophages accumulated and supported the efficient replication of superinfecting LDV-P. Therefore, although neuropathogenic LDVs possess the unique ability to infect anterior horn neurons of ADPM-susceptible mice, they exhibit a reduced ability to establish a persistent infection in peripheral tissues of mice regardless of the strain. The specific suppression of LDV-C replication in persistently infected mice is probably due in part to a more efficient neutralization of LDV-C than LDV-P by antibodies to the primary envelope glycoprotein, VP-3P. Both neuropathogenicity and the higher sensitivity to antibody neutralization correlated with the absence of two of three N-linked polylactosaminoglycan chains on the ca. 30-amino-acid ectodomain of VP-3P, which seems to carry the neutralization epitope(s) and forms part of the virus receptor attachment site.",,"['Chen, Z', 'Rowland, R R', 'Anderson, G W', 'Palmer, G A', 'Plagemann, P G']",,,,
,PMC,The abundant latency-associated transcripts of herpes simplex virus type 1 are bound to polyribosomes in cultured neuronal cells and during latent infection in mouse trigeminal ganglia.,,PMC191416,,,"During herpes simplex virus type 1 (HSV-1) latency, limited viral transcription takes place. This transcription has been linked to the ability of the HSV-1 genome to reactivate and consists of abundant 2.0- and 1.5-kb collinear latency-associated transcripts (LATs), spanned by minor hybridizing RNA (mLAT). The 1.5-kb LAT is derived from the 2.0-kb LAT by splicing, and both transcripts contain two large overlapping open reading frames. The molecular action mechanisms of the latency-associated gene expression are unknown, and no HSV-1 latency-encoded proteins have been convincingly demonstrated. We have cloned the entire latency-associated transcriptionally active HSV-1 DNA fragment (10.4 kb) under control of a constitutive promoter and generated a neuronal cell line (NA4) stably transfected with the viral LAT's region. NA4 cells produced the 2.0- and the 1.5-kb LATs. Northern blotting and reverse transcription-PCR analysis of RNA from NA4 cells and from trigeminal ganglia of mice latently infected with HSV-1 revealed that the two abundant LAT species were present in the polyribosomal RNA fractions. After addition of EDTA, which causes dissociation of mRNA-ribosome complexes, both LATs could be detected only in subpolyribosomal, but not in polyribosomal fractions. These results show that (i) HSV-1 LATs are bound to polyribosomes during latency in vivo, as well as in neuronal cells in vitro, and therefore might be translated, and that (ii) the NA4 cell line is a suitable tool with which to look for HSV-1 latency-encoded gene products.",,"['Goldenberg, D', 'Mador, N', 'Ball, M J', 'Panet, A', 'Steiner, I']",,,,
,PMC,"RNA-RNA recombination in Sindbis virus: roles of the 3' conserved motif, poly(A) tail, and nonviral sequences of template RNAs in polymerase recognition and template switching.",,PMC191391,,,"Sindbis virus (SIN), a mosquito-transmitted animal RNA virus, carries a 11.7-kb positive-sense RNA genome which is capped and polyadenylated. We recently reported that the SIN RNA-dependent RNA polymerase (RdRp) could initiate negative-strand RNA synthesis from a 0.3-kb 3'-coterminal SIN RNA fragment and undergo template switching in vivo (M. Hajjou, K. R. Hill, S. V. Subramaniam, J. Y. Hu, and R. Raju, J. Virol. 70:5153-5164, 1996). To identify and characterize the viral and nonviral sequences which regulate SIN RNA synthesis and recombination, a series of SIN RNAs carrying altered 3' ends were tested for the ability to produce infectious virus or to support recombination in BHK cells. The major findings of this report are as follows: (i) the 3'-terminal 20-nucleotides (nt) sequence along with the abutting poly(A) tail of the SIN genome fully supports negative-strand synthesis, genome replication, and template switching; (ii) a full-length SIN RNA carrying the 3'-terminal 24 nt but lacking the poly(A) tail is noninfectious; (iii) SIN RNAs which carry 3' 64 nt or more without the poly(A) tail are infectious and regain their poly(A) tail in vivo; (iv) donor templates lacking the poly(A) tail do not support template switching; (v) full-length SIN RNAs lacking the poly(A) tail but carrying 3' nonviral extensions, although debilitated to begin with, evolve into rapidly growing poly(A)-carrying mutants; (vi) poly(A) or poly(U) motifs positioned internally within the acceptor templates, in the absence of other promoter elements within the vicinity, do not induce the jumping polymerase to reinitiate at these sites; and (vii) the junction site selection on donor templates occurs independently of the sequences around the acceptor sites. In addition to furthering our understanding of RNA recombination, these studies give interesting clues as to how the alphavirus polymerase interacts with its 3' promoter elements of genomic RNA and nonreplicative RNAs. This is the first report that an in vitro-synthesized alphavirus RNA lacking a poly(A) tail can initiate infection and produce 3' polyadenylated viral genome in vivo.",,"['Hill, K R', 'Hajjou, M', 'Hu, J Y', 'Raju, R']",,,,
,PMC,Virus-encoded RNA helicases.,,PMC191378,,,,,"['Kadaré, G', 'Haenni, A L']",,,,
,PMC,The Drosophila suppressor of sable protein binds to RNA and associates with a subset of polytene chromosome bands.,,PMC232078,,,"Mutations of the Drosophila melanogaster suppressor of sable [su(s)] gene, which encodes a 150-kDa nuclear protein [Su(s)], increase the accumulation of specific transcripts in a manner that is not well understood but that appears to involve pre-mRNA processing. Here, we report biochemical analysis of purified, recombinant Su(s) [rSu(s)] expressed in baculovirus and in Escherichia coli as maltose binding protein (MBP) fusions and immunocytochemical analysis of endogenous Su(s). This work has shown that purified, baculovirus-expressed rSu(s) binds to RNA in vitro with a high affinity and limited specificity. Systematic evolution of ligands by exponential enrichment was used to identify preferred RNA targets of rSu(s), and a large proportion of RNAs isolated contain a full or partial match to the consensus sequence UCAGUAGUCU, which was confirmed to be a high-affinity rSu(s) binding site. An MBP-Su(s) fusion protein containing the N-terminal third of Su(s) binds RNAs containing this sequence with a higher specificity than full-length, baculovirus-expressed rSu(s). The consensus sequence resembles both a cryptic 5' splice site and a sequence that is found near the 5' end of some Drosophila transcripts. Immunolocalization studies showed that endogenous Su(s) is distributed in a reticulated pattern in Drosophila embryo and salivary gland nuclei. In salivary gland cells, Su(s) is found both in the nucleoplasm and in association with a subset of polytene chromosome bands. Considering these and previous results, we propose two models to explain how su(s) mutations affect nuclear pre-mRNA processing.",,"['Murray, M V', 'Turnage, M A', 'Williamson, K J', 'Steinhauer, W R', 'Searles, L L']",,,,
,PMC,Mechanisms of virus induced exacerbations of asthma,,PMC1758527,,,,,"['Corne, J. M.', 'Holgate, S. T.']",,,,
,PMC,An NMR and mutational study of the pseudoknot within the gene 32 mRNA of bacteriophage T2: insights into a family of structurally related RNA pseudoknots.,,PMC146565,,,"NMR methods were used to investigate a series of mutants of the pseudoknot within the gene 32 messenger RNA of bacteriophage T2, for the purpose of investigating the range of sequences, stem and loop lengths that can form a similar pseudoknot structure. This information is of particular relevance since the T2 pseudoknot has been considered a representative of a large family of RNA pseudoknots related by a common structural motif, previously referred to as 'common pseudoknot motif 1' or CPK1. In the work presented here, a mutated sequence with the potential to form a pseudoknot with a 6 bp stem2 was shown to adopt a pseudoknot structure similar to that of the wild-type sequence. This result is significant in that it demonstrates that pseudoknots with 6 bp in stem2 and a single nucleotide in loop1 are indeed feasible. Mutated sequences with the potential to form pseudoknots with either 5 or 8 bp in stem2 yielded NMR spectra that could not confirm the formation of a pseudoknot structure. Replacing the adenosine nucleotide in loop1 of the wild-type pseudoknot with any one of G, C or U did not significantly alter the pseudoknot structure. Taken together, the results of this study provide support for the existence of a family of similarly structured pseudoknots with two coaxially stacked stems, either 6 or 7 bp in stem2, and a single nucleotide in loop1. This family includes many of the pseudoknots predicted to occur downstream of the frameshift or readthrough sites in a significant number of viral RNAs.",,"['Du, Z', 'Hoffman, D W']",,,,
,PMC,A practical guide for the diagnosis and treatment of pediatric pneumonia,,PMC1232848,,,,,"['Jadavji, T.', 'Law, B.', 'Lebel, M. H.', 'Kennedy, W. A.', 'Gold, R.', 'Wang, E. E. L.']",,,,
,PMC,Mouse hepatitis viral infection induces an extrathymic differentiation of the specific intrahepatic alpha beta-TCRintermediate LFA-1high T-cell population.,,PMC1456597,,,"Mouse hepatitis virus type 3 (MHV3), a coronavirus, is an excellent model for the study of thymic and extrathymic T-cell subpopulation disorders induced during viral hepatitis. It was recently reported that, in addition to the intrathymic T-cell differentiation pathway, an extrathymic differentiation pathway of alpha beta-T-cell receptor (TCR) T lymphocytes exists in the liver, and becomes important under pathological situations such as autoimmune diseases, malignancies or hepatic bacterial infections. In the present study, we compared the phenotypes of resident hepatic, splenic or thymic T-cell subpopulations during the acute viral hepatitis induced by HMV3 in susceptible C57BL/6 mice. The number of liver-resident mononuclear cells (MNC) increased during the viral infection, while cellularity decreased. Single positive (SP) CD4+ cells strongly increased in both the liver and thymus, while double positive (DP) (CD4+ CD8+) cells, present in the liver and thymus of mock-infected mice, decreased in C57BL/6 mice during the viral infection. A shift of alpha beta-TCRintermediate T cells toward alpha beta-TCRhigh was evidenced in the liver and thymus of infected mice, but not in the spleen. The few alpha beta-TCRint double negative (DN) (CD4-CD8-) cells also decreased following viral infection. alpha beta-TCRint or high lymphocytes expressing high levels of leucocyte function antigen-1 (LFA-1) increased in the liver of MHV3-infected mice. In addition, liver-resident T cells expressed strongly the CD44 (Pgp-1) activation marker, suggesting that they were either activated or antigen experienced during the viral infection. No significant change in T-cell subpopulations was detected in the spleen, suggesting that MHV3 infection could induce an early in situ differentiation of resident hepatic T cells rather than a recruitment of lymphocytes from peripheral lymphoid organs.",,"['Lamontagne, L', 'Massicotte, E', 'Page, C']",,,,
,PMC,Development of a nested PCR assay for detection of feline infectious peritonitis virus in clinical specimens.,,PMC229648,,,"A diagnostic test for feline infectious peritonitis virus (FIPV) infection based on a nested PCR (nPCR) assay was developed and tested with FIPV, feline enteric coronavirus (FECV), canine coronavirus (CCV), and transmissible gastroenteritis virus (TGEV) and clinical fluid samples from cats with effusive feline infectious peritonitis (FIP). The target sequence for the assay is in the S1 region of the peplomer protein E2 gene. A vaccine strain of FIPV and two wild-type FIPV strains tested positive, but FECV, TGEV, and CCV tested negative. Preliminary tests with 12 cats with clinical evidence of effusive FIP and 11 cats with an illness associated with effusions, but attributed to other causes, were performed. Eleven of the 12 cats with effusive FIP tested positive, while 1 was negative. Ten of the 11 cats ill from other causes tested negative, while 1 was positive. On the basis of clinical laboratory and histopathologic criteria, the preliminary sensitivity and specificity of the assay were 91.6 and 94%, respectively.",,"['Gamble, D A', 'Lobbiani, A', 'Gramegna, M', 'Moore, L E', 'Colucci, G']",,,,
,PMC,An RNA tertiary structure in the 3' untranslated region of enteroviruses is necessary for efficient replication.,,PMC191346,,,"RNA tertiary structures, such as pseudoknots, are known to be biologically significant in a number of virus systems. The 3' untranslated regions of the RNA genomes of all members of the Enterovirus genus of Picornaviridae exhibit a potential, pseudoknot-like, tertiary structure interaction of an unusual type. This is formed by base pairing between loop regions of two secondary structure domains. It is distinct from a potential, conventional pseudoknot, studied previously in poliovirus, which is less conserved phylogenetically. We have analyzed the tertiary structure feature in one enterovirus, coxsackievirus A9, using specific mutagenesis. A double mutant in which the potential interaction was destroyed was nonviable, and viability was restored by introducing compensating mutations, predicted to allow the interaction to reform. Phenotypic pseudorevertants of virus mutants, having mutations designed to disrupt the interaction, were all found to have acquired nucleotide changes which restored the potential interaction. Analysis of one mutant containing a single-base mutation indicated a greatly increased temperature sensitivity due to a step early in replication. The results show that, in addition to secondary structures, tertiary RNA structural interactions can play an important role in the biology of picornaviruses.",,"['Mirmomeni, M H', 'Hughes, P J', 'Stanway, G']",,,,
,PMC,Disassociation between the in vitro and in vivo effects of nitric oxide on a neurotropic murine coronavirus.,,PMC191327,,,"Intranasal inoculation of the neuroattenuated OBLV60 strain of mouse hepatitis virus results in infection of mitral neurons in the olfactory bulb, followed by spread along olfactory and limbic pathways to the brain. Immunocompetent BALB/c mice were able to clear virus by 11 days postinfection (p.i.). Gamma interferon (IFN-gamma) may play a role in clearance of OBLV60 from infected immunocompetent BALB/c mice through a nonlytic mechanism. Among the variety of immunomodulatory activities of IFN-gamma is the induction of expression of inducible nitric oxide synthase (iNOS), an enzyme responsible for the production of nitric oxide (NO). Studies were undertaken to investigate the role of IFN-gamma and NO in host defense and clearance of OBLV60 from the central nervous system (CNS). Exposure of OBLV60-infected OBL21a cells, a mouse neuronal cell line, to the NO-generating compound S-nitroso-L-acetyl penicillamine resulted in a significant decrease in viral replication, indicating that NO interfered with viral replication. Furthermore, infection of IFN-gamma knockout (GKO) mice and athymic nude mice with OBLV60 resulted in low-level expression of iNOS mRNA and protein in the brains compared to that of OBLV60-infected BALB/c mice. Nude mice were unable to clear virus and eventually died between days 11 and 14 p.i. (B. D. Pearce, M. V. Hobbs, T. S. McGraw, and M. J. Buchmeier, J. Virol. 68:5483-5495, 1994); however, GKO mice survived infection and cleared virus by day 18 p.i. These data suggest that IFN-gamma production in the olfactory bulb contributed to but may not be essential for clearance of OBLV60 from the brain. In addition, treatment of OBLV60-infected BALB/c mice with aminoguanidine, a selective inhibitor of iNOS activity, did not result in any increase in mortality, and the mice cleared the virus by 11 days p.i. These data suggest that although NO was able to block replication of virus in vitro, expression of iNOS with NO release in vivo did not appear to be the determinant factor in clearance of OBLV60 from CNS neurons.",,"['Lane, T E', 'Paoletti, A D', 'Buchmeier, M J']",,,,
,PMC,Site-directed and linker insertion mutagenesis of herpes simplex virus type 1 glycoprotein H.,,PMC191323,,,"The gH-gL complex of herpes simplex virus type 1 (HSV-1) is essential for virion infectivity and virus-induced cell fusion, but functional domains of the gH molecule remain to be defined. We have addressed this question by mutagenesis. A set of linker insertion mutants in HSV-1 gH was generated and tested in transient assays for their ability to complement a gH-negative virus. Insertions at three sites in the C-terminal third of the external domain affected the ability of gH to function in cell-cell fusion and virus entry, while insertions at six sites in the N-terminal half of the external domain induced conformational changes in gH such that it was not recognized by monoclonal antibody LP11, although expression at the cell surface was unchanged. A recombinant virus in which a potential integrin-binding motif, RGD, in gH was changed to the triplet RGE entered cells as efficiently as the wild type, indicating that HSV-1 entry is not mediated by means of the gH-RGD motif binding to cell surface integrins. Furthermore, mutagenesis of the glycosylation site which is positionally conserved in all herpesvirus gH sequences in close proximity to the transmembrane domain generated a recombinant virus that grew in vitro with wild-type single-step kinetics.",,"['Galdiero, M', 'Whiteley, A', 'Bruun, B', 'Bell, S', 'Minson, T', 'Browne, H']",,,,
,PMC,Episodic evolution mediates interspecies transfer of a murine coronavirus.,,PMC191277,,,"Molecular mechanisms permitting the establishment and dissemination of a virus within a newly adopted host species are poorly understood. Mouse hepatitis virus (MHV) strains (MHV-A59, MHV-JHM, and MHV-A59/MHV-JHM) were passaged in mixed cultures containing progressively increasing concentrations of nonpermissive Syrian baby hamster kidney (BHK) cells and decreasing concentrations of permissive murine DBT cells. From MHV-A59/MHV-JHM mixed infection, variant viruses (MHV-H1 and MHV-H2) which replicated efficiently in BHK cells were isolated. Under identical treatment conditions, the parental MHV-A59 or MHV-JHM strains failed to produce infectious virus or transcribe detectable levels of viral RNA or protein. The MHV-H isolates were polytrophic, replicating efficiently in normally nonpermissive Syrian hamster smooth muscle (DDT-1), Chinese hamster ovary (CHO), human adenocarcinoma (HRT), primate kidney (Vero), and murine 17Cl-1 cell lines. Little if any virus replication was detected in feline kidney (CRFK) and porcine testicular (ST) cell lines. The variant virus, MHV-H2, transcribed seven mRNAs equivalent in relative abundance and size to those synthesized by the parental virus strains. MHV-H2 was an RNA recombinant virus containing a crossover site in the S glycoprotein gene. At the molecular level, episodic evolution and positive Darwinian natural selection were apparent within the MHV-H2 S and HE glycoprotein genes. These findings differ from the hypothesis that neutral changes are the predominant feature of molecular evolution and argue that changing ecologies actuate episodic evolution in the MHV spike glycoprotein genes that govern interspecies transfer and spread into alternative hosts.",,"['Baric, R S', 'Yount, B', 'Hensley, L', 'Peel, S A', 'Chen, W']",,,,
,PMC,Characterization of early stages in vaccinia virus membrane biogenesis: implications of the 21-kilodalton protein and a newly identified 15-kilodalton envelope protein.,,PMC191252,,,"Vaccinia virus (VV) membrane biogenesis is a poorly understood process. It has been proposed that cellular membranes derived from the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) are incorporated in the early stages of virion assembly. We have recently shown that the VV 21-kDa (A17L gene) envelope protein is essential for the formation of viral membranes. In the present work, we identify a 15-kDa VV membrane protein encoded by the A14L gene. This protein is phosphorylated and myristylated during infection and is incorporated into the virion envelope. Both the 21- and 15-kDa proteins are found associated with cellular tubulovesicular elements related to the ERGIC, suggesting that these proteins are transported in these membranes to the nascent viral factories. When synthesis of the 21-kDa protein is repressed, organized membranes are not formed but numerous ERGIC-derived tubulovesicular structures containing the 15-kDa protein accumulate in the boundaries of the precursors of the viral factories. These data suggest that the 21-kDa protein is involved in organizing the recruited viral membranes, while the 15-kDa protein appears to be one of the viral elements participating in the membrane recruitment process from the ERGIC, to initiate virus formation.",,"['Rodríguez, J R', 'Risco, C', 'Carrascosa, J L', 'Esteban, M', 'Rodríguez, D']",,,,
,PMC,Proteolytic processing of the coronavirus infectious bronchitis virus 1a polyprotein: identification of a 10-kilodalton polypeptide and determination of its cleavage sites.,,PMC191251,,,"Proteolytic processing of the polyprotein encoded by mRNA 1 is an essential step in coronavirus RNA replication and gene expression. We have previously reported that an open reading frame (ORF) 1a-specific proteinase of the picornavirus 3C proteinase group is involved in processing of the coronavirus infectious bronchitis virus (IBV) 1a/1b polyprotein, leading to the formation of a mature viral protein of 100 kDa. We report here the identification of a novel 10-kDa polypeptide and the involvement of the 3C-like proteinase in processing of the ORF 1a polyprotein to produce the 10-kDa protein species. By using a region-specific antiserum, V47, raised against a bacterial-viral fusion protein containing IBV sequence encoded between nucleotides 11488 and 12600, the 10-kDa polypeptide was detected in lysates from both IBV-infected and plasmid DNA-transfected Vero cells. Coexpression, deletion, and mutagenesis studies showed that this novel polypeptide was encoded by ORF 1a from nucleotide 11545 to 11878 and was cleaved from the 1a polyprotein by the 3C-like proteinase domain. Evidence presented suggested that a previously predicted Q-S (Q3783 S3784) dipeptide bond encoded by ORF 1a between nucleotides 11875 and 11880 was responsible for the release of the C terminus of the 10-kDa polypeptide and that a novel Q-N (Q3672 N3673) dipeptide bond encoded between nucleotides 11542 and 11547 was responsible for the release of the N terminus of the 10-kDa polypeptide.",,"['Liu, D X', 'Xu, H Y', 'Brown, T D']",,,,
,PMC,Antiviral immune responses in CTLA4 transgenic mice.,,PMC191249,,,"The role of B7 binding CD28 in the regulation of T- and B-cell responses against viral antigens was assessed in transgenic mice expressing soluble CTLA4-Hgamma1 (CTLA4-Ig tg mice) that blocks B7-CD28 interactions. The results indicate that transgenic soluble CTLA4 does not significantly alter cytotoxic T-cell responses against replicating lymphocytic choriomeningitis virus (LCMV) or vaccinia virus but drastically impairs the induction of cytotoxic T-cell responses against abortively replicating vesicular stomatitis virus (VSV). While the T-independent neutralizing immunoglobulin M (IgM) responses were within normal ranges, the switch to IgG was reduced 4- to 16-fold after immunization with abortively replicating VSV and more than 30-fold after immunization with an inert VSV glycoprotein antigen in transgenic mice. IgG antibody responses to LCMV, as detected by enzyme-linked immunosorbent assay and by neutralizing action, were reduced about 3- to 20-fold and more than 50-fold, respectively. These results suggest that responses in CTLA4-Ig tg mice are mounted according to their independence of T help. While immune responses to nonreplicating or poorly replicating antigens are in general most dependent on T help and B7-CD28 interactions, they are most impaired in CTLA4-Ig tg mice. The results of the present experiments also indicate that highly replicating viruses, because of greater quantities of available antigens and by inducing as-yet-undefined factors and/or cell surface changes, are capable of compensating for the decrease in T help caused by the blocking effects of soluble CTLA4.",,"['Zimmermann, C', 'Seiler, P', 'Lane, P', 'Zinkernagel, R M']",,,,
,PMC,An infectious arterivirus cDNA clone: Identification of a replicase point mutation that abolishes discontinuous mRNA transcription,,PMC19627,,,"Equine arteritis virus (EAV) is a positive-strand RNA virus that uses a discontinuous transcription mechanism to generate a nested set of six subgenomic mRNAs from which its structural genes are expressed. A stable bacterial plasmid (pEAV030) containing a full-length cDNA copy of the 12.7-kb EAV genome was constructed. After removal of a single point mutation in the replicase gene, RNA transcripts generated in vitro from pEAV030 were shown to be infectious upon electroporation into BHK-21 cells. A genetic marker mutation was introduced at the cDNA level and recovered from the genome of the progeny virus. The potential of pEAV030 as a tool to express foreign genes was demonstrated by the efficient expression of the chloramphenicol acetyltransferase (CAT) reporter gene from two different subgenomic mRNAs. The point mutation that initially rendered the full-length clone noninfectious was found to result in a particularly intriguing phenotype: RNA carrying this mutation can replicate efficiently but does not produce the subgenomic mRNAs required for structural protein expression. To our knowledge, this mutant provides the first evidence that the requirements for arterivirus genome replication and discontinuous mRNA synthesis are, at least partially, different and that these processes may be separated experimentally.",,"['van Dinten, Leonie\u2009C.', 'den Boon, Johan\u2009A.', 'Wassenaar, Alfred\u2009L.\u2009M.', 'Spaan, Willy\u2009J.\u2009M.', 'Snijder, Eric\u2009J.']",,,,
,PMC,Isolation of Streptococcus suis from a young wild boar.,,PMC1576536,,,,,"['Higgins, R', 'Lagacé, A', 'Messier, S', 'Julien, L']",,,,
,PMC,Human carcinoembryonic antigen and biliary glycoprotein can serve as mouse hepatitis virus receptors.,,PMC191232,,,"Receptors for murine coronavirus mouse hepatitis virus (MHV) are members of the murine carcinoembryonic antigen (CEA) gene family. Since MHV can also infect primates and cause central nervous system lesions (G. F. Cabirac et al., Microb. Pathog. 16:349-357, 1994; R. S. Murray et al., Virology 188:274-284, 1992), we examined whether human CEA-related molecules can be used by MHV as potential receptors. Transfection of plasmids expressing human carcinoembryonic antigen (hCEA) and human biliary glycoprotein into COS-7 cells, which lack a functional MHV receptor, conferred susceptibility to two MHV strains, A59 and MHV-2. Domain exchange experiments between human and murine CEA-related molecules identified the immunoglobulin-like loop I of hCEA as the region conferring the virus-binding specificity. This finding expands the potential MHV receptors to primate species.",,"['Chen, D S', 'Asanaka, M', 'Chen, F S', 'Shively, J E', 'Lai, M M']",,,,
,PMC,Persistent poliovirus infection in mouse motoneurons.,,PMC191220,,,"Poliovirus (PV) is the causal agent of paralytic poliomyelitis. Many survivors of the acute disease, after decades of clinical stability, develop new muscular symptoms called postpolio syndrome. It has been hypothesized that the persistence of PV in the spinal cord is involved in the etiology of this syndrome. To investigate the ability of PV to persist in the spinal cord after the onset of paralysis, we exploited a mouse model in which most animals inoculated with a mouse-adapted mutant survived after the onset of paralysis. Light microscopy and ultrastructural immunohistochemical studies and reverse transcription followed by nested PCR performed on spinal cord from paralyzed mice demonstrated that PV persisted in the mouse spinal cord for at least 12 months after the onset of paralysis. This mouse model provides a new tool for studying poliomyelitis evolution after the onset of paralysis.",,"['Destombes, J', 'Couderc, T', 'Thiesson, D', 'Girard, S', 'Wilt, S G', 'Blondel, B']",,,,
,PMC,Identification and characterization of a G protein-coupled receptor homolog encoded by murine cytomegalovirus.,,PMC191209,,,"This report describes the identification of a murine cytomegalovirus (MCMV) G protein-coupled receptor (GCR) homolog. This open reading frame (M33) is most closely related to, and collinear with, human cytomegalovirus UL33, and homologs are also present in human herpesvirus 6 and 7 (U12 for both viruses). Conserved counterparts in the sequenced alpha- or gammaherpesviruses have not been identified to date, suggesting that these genes encode proteins which are important for the biological characteristics of betaherpesviruses. We have detected transcripts for both UL33 and M33 as early as 3 or 4 h postinfection, and these reappear at late times. In addition, we have identified N-terminal splicing for both the UL33 and M33 RNA transcripts. For both open reading frames, splicing results in the introduction of amino acids which are highly conserved among known GCRs. To characterise the function of the M33 in the natural host, two independent MCMV recombinant viruses were prepared, each of which possesses an M33 open reading frame which has been disrupted with the beta-galactosidase gene. While the recombinant M33 null viruses showed no phenotypic differences in replication from wild-type MCMV in primary mouse embryo fibroblasts in vitro, they showed severely restricted growth in the salivary glands of infected mice. These data suggest that M33 plays an important role in vivo, in particular in the dissemination to or replication in the salivary gland, and provide the first evidence for the function of a viral GCR homolog in vivo.",,"['Davis-Poynter, N J', 'Lynch, D M', 'Vally, H', 'Shellam, G R', 'Rawlinson, W D', 'Barrell, B G', 'Farrell, H E']",,,,
,PMC,Reovirus variants selected during persistent infections of L cells contain mutations in the viral S1 and S4 genes and are altered in viral disassembly.,,PMC191191,,,"Reoviruses isolated from persistently infected cultures (PI viruses) can grow in the presence of ammonium chloride, a weak base that blocks acid-dependent proteolysis of viral outer-capsid proteins during viral entry into cells. We used reassortant viruses isolated from crosses of wild-type (wt) reovirus strain, type 1 Lang, and three independent PI viruses, L/C, PI 2A1, and PI 3-1, to identify viral genes that segregate with the capacity of PI viruses to grow in cells treated with ammonium chloride. Growth of reassortant viruses in ammonium chloride-treated cells segregated with the S1 gene of L/C and the S4 gene of PI 2A1 and PI 3-1. The S1 gene encodes viral attachment protein sigma1, and the S4 gene encodes outer-capsid protein sigma3. To identify mutations in sigma3 selected during persistent reovirus infection, we determined the S4 gene nucleotide sequences of L/C, PI 2A1, PI 3-1, and four additional PI viruses. The deduced amino acid sequences of sigma3 protein of six of these PI viruses contained a tyrosine-to-histidine substitution at residue 354. To determine whether mutations selected during persistent infection alter cleavage of the viral outer capsid, the fate of viral structural proteins was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after treatment of virions of wt and PI viruses with chymotrypsin in vitro. Proteolysis of PI virus outer-capsid proteins sigma3 and mu1C occurred with faster kinetics than proteolysis of wt virus outer-capsid proteins. These results demonstrate that mutations in either the S1 or S4 gene alter acid-dependent disassembly of the reovirus outer capsid and suggest that increased efficiency of proteolysis of viral outer-capsid proteins is important for maintenance of persistent reovirus infections of cultured cells.",,"['Wetzel, J D', 'Wilson, G J', 'Baer, G S', 'Dunnigan, L R', 'Wright, J P', 'Tang, D S', 'Dermody, T S']",,,,
,PMC,Immunocytochemical analysis of Uukuniemi virus budding compartments: role of the intermediate compartment and the Golgi stack in virus maturation.,,PMC191169,,,"Previous studies have suggested that Uukuniemi virus, a bunyavirus, matures at the membranes of the Golgi complex. In this study we have employed immunocytochemical techniques to analyze in detail the budding compartment(s) of the virus. Electron microscopy of infected BHK-21 cells showed that virus particles are found in the cisternae throughout the Golgi stack. Within the cisternae, the virus particles were located preferentially in the dilated rims. This would suggest that virus budding may begin at or before the cis Golgi membranes. The virus budding compartment was studied further by immunoelectron microscopy with a pre-Golgi intermediate compartment marker, p58, and a Golgi stack marker protein, mannosidase II (ManII). Virus particles and budding virus were detected in ManII-positive Golgi stack membranes and, interestingly, in both juxtanuclear and peripheral p58-positive elements of the intermediate compartment. In cells incubated at 15 degrees C the nucleocapsid and virus envelope proteins were seen to accumulate in the intermediate compartment. Immunoelectron microscopy demonstrated that at 15 degrees C the nucleocapsid is associated with membranes that show a characteristic distribution and tubulo-vesicular morphology of the pre-Golgi intermediate compartment. These membranes contained virus particles in the lumen. The results indicate that the first site of formation of Uukuniemi virus particles is the pre-Golgi intermediate compartment and that virus budding continues in the Golgi stack. The results raise questions about the intracellular transport pathway of the virus particles, which are 100 to 120 nm in diameter and are therefore too large to be transported in the 60-nm-diameter vesicles postulated to function in the intra-Golgi transport. The distribution of the virus in the Golgi stack may imply that the cisternae themselves have a role in the vectorial transport of virus particles.",,"['Jäntti, J', 'Hildén, P', 'Rönkä, H', 'Mäkiranta, V', 'Keränen, S', 'Kuismanen, E']",,,,
,PMC,The internal open reading frame within the nucleocapsid gene of mouse hepatitis virus encodes a structural protein that is not essential for viral replication.,,PMC191149,,,"The coronavirus mouse hepatitis virus (MHV) contains a large open reading frame embedded entirely within the 5' half of its nucleocapsid (N) gene. This internal gene (designated I) is in the +1 reading frame with respect to the N gene, and it encodes a mostly hydrophobic 23-kDa polypeptide. We have found that this protein is expressed in MHV-infected cells and that it is a previously unrecognized structural protein of the virion. To analyze the potential biological importance of the I gene, we disrupted its expression by site-directed mutagenesis using targeted RNA recombination. The start codon for I was replaced by a threonine codon, and a stop codon was introduced at a short interval downstream. Both alterations created silent changes in the N reading frame. In vitro translation studies showed that these mutations completely abolished synthesis of I protein, and immunological analysis of infected cell lysates confirmed this conclusion. The MHV I mutant was viable and grew to high titer. However, the I mutant had a reduced plaque size in comparison with its isogenic wild-type counterpart, suggesting that expression of I confers some minor growth advantage to the virus. The engineered mutations were stable during the course of experimental infection in mice, and the I mutant showed no significant differences from wild type in its ability to replicate in the brains or livers of infected animals. These results demonstrate that I protein is not essential for the replication of MHV either in tissue culture or in its natural host.",,"['Fischer, F', 'Peng, D', 'Hingley, S T', 'Weiss, S R', 'Masters, P S']",,,,
,PMC,Characterization of two temperature-sensitive mutants of coronavirus mouse hepatitis virus strain A59 with maturation defects in the spike protein.,,PMC191143,,,"Two temperature-sensitive (ts) mutants of mouse hepatitis virus strain A59, ts43 and ts379, have been described previously to be ts in infectivity but unaffected in RNA synthesis (M. J. M. Koolen, A. D. M. E. Osterhaus, G. van Steenis, M. C. Horzinek, and B. A. M. van der Zeijst, Virology 125:393-402, 1983). We present a detailed analysis of the protein synthesis of the mutant viruses at the permissive (31 degrees C) and nonpermissive (39.5 degrees C) temperatures. It was found that synthesis of the nucleocapsid protein N and the membrane protein M of both viruses was insensitive to temperature. However, the surface protein S of both viruses was retained in the endoplasmic reticulum at the nonpermissive temperature. This was shown first by analysis of endoglycosidase H-treated and immunoprecipitated labeled S proteins. The mature Golgi form of S was not present at the nonpermissive temperature for the ts viruses, in contrast to wild-type (wt) virus. Second, gradient purification of immunoprecipitated S after pulse-chase labeling showed that only wt virus S was oligomerized. We conclude that the lack of oligomerization causes the retention of the ts S proteins in the endoplasmic reticulum. As a result, ts virus particles that were devoid of S were produced at the nonpermissive temperature. This result could be confirmed by biochemical analysis of purified virus particles and by electron microscopy.",,"['Luytjes, W', 'Gerritsma, H', 'Bos, E', 'Spaan, W']",,,,
,PMC,Characterization of a second cleavage site and demonstration of activity in trans by the papain-like proteinase of the murine coronavirus mouse hepatitis virus strain A59.,,PMC191137,,,"The 21.7-kb replicase locus of mouse hepatitis virus strain A59 (MHV-A59) encodes several putative functional domains, including three proteinase domains. Encoded closest to the 5' terminus of this locus is the first papain-like proteinase (PLP-1) (S. C. Baker et al., J. Virol. 67:6056-6063, 1993; H.-J. Lee et al., Virology 180:567-582, 1991). This cysteine proteinase is responsible for the in vitro cleavage of p28, a polypeptide that is also present in MHV-A59-infected cells. Cleavage at a second site was recently reported for this proteinase (P. J. Bonilla et al., Virology 209:489-497, 1995). This new cleavage site maps to the same region as the predicted site of the C terminus of p65, a viral polypeptide detected in infected cells. In this study, microsequencing analysis of the radiolabeled downstream cleavage product and deletion mutagenesis analysis were used to identify the scissile bond of the second cleavage site to between Ala832 and Gly833. The effects of mutations between the P5 and P2' positions on the processing at the second cleavage site were analyzed. Most substitutions at the P4, P3, P2, and P2' positions were permissive for cleavage. With the exceptions of a conservative P1 mutation, Ala832Gly, and a conservative P5 mutation, Arg828Lys, substitutions at the P5, P1, and P1' positions severely diminished second-site proteolysis. Mutants in which the p28 cleavage site (Gly247 / Val248) was replaced by the Ala832 / Gly833 cleavage site and vice versa were found to retain processing activity. Contrary to previous reports, we determined that the PLP-1 has the ability to process in trans at either the p28 site or both cleavage sites, depending on the choice of substrate. The results from this study suggest a greater role by the PLP-1 in the processing of the replicase locus in vivo.",,"['Bonilla, P J', 'Hughes, S A', 'Weiss, S R']",,,,
,PMC,Prednisolone at anti-inflammatory or immunosuppressive dosages in conjunction with doxycycline does not potentiate the severity of Rickettsia rickettsii infection in dogs.,,PMC163675,,,"Dogs were experimentally inoculated with Rickettsia rickettsii to determine if anti-inflammatory or immunosuppressive dosages of prednisolone, when administered in conjunction with an antirickettsial antibiotic (doxycycline), induced therapeutically relevant pathophysiological consequences that ultimately influence disease outcome. Although the duration of rickettsemia was prolonged in dogs receiving immunosuppressive, but not anti-inflammatory, corticosteroids, concurrent administration of doxycycline and corticosteroids conferred no other detected detrimental effects. Treatment with doxycycline or doxycycline in conjunction with prednisolone resulted in decreased R. rickettsii-specific antibody titers; however, examination of appropriately timed acute- and convalescent-phase serum samples would have facilitated an accurate diagnosis of Rocky Mountain spotted fever (RMSF) in all 16 dogs. We conclude that the concurrent use of anti-inflammatory or immunosuppressive doses of prednisolone in conjunction with doxycycline, early in the course of experimental RMSF, confers no clinically relevant detrimental effects and that additional studies might be indicated to detect possible beneficial effects in cases of severe or potentially fulminant RMSF. However, because the illness induced in these dogs was of mild to moderate severity, the results of this study should definitely not be construed as supporting the safety or efficacy of prednisolone for treatment of severe canine or human RMSF.",,"['Breitschwerdt, E B', 'Davidson, M G', 'Hegarty, B C', 'Papich, M G', 'Grindem, C B']",,,,
,PMC,Experimental Escherichia coli O157:H7 carriage in calves.,,PMC168298,,,"Nine weaned calves (6 to 8 weeks of age) were given 10(10) CFU of a five-strain mixture of enterohemorrhagic Escherichia coli O157:H7 by oral-gastric intubation. After an initial brief period of pyrexia in three calves and transient mild diarrhea in five calves, calves were clinically normal throughout the 13- to 27-day study. The population of E. coli O157:H7 in the faces decreased dramatically in all calves during the first 2 weeks after inoculation. Thereafter, small populations of E. coli O157:H7 persisted in all calves, where they were detected intermittently in the feces and rumen contents. While withholding food increased fecal shedding of E. coli O157:H7 by 1 to 2 log10/g in three of four calves previously shedding small populations of E. coli O157:H7, the effect of fasting on fecal shedding of E. coli O157:H7 was variable in calves shedding larger populations. At necropsy, E. coli O157:H7 was not isolated from sites outside the alimentary tract. E. coli O157:H7 was isolated from the forestomach or colon of all calves at necropsy. Greater numbers of E. coli O157:H7 were present in the gastrointestinal contents than in the corresponding mucosal sections, and there was no histologic or immunohistochemical evidence of E. coli O157:H7 adhering to the mucosa. In conclusion, under these experimental conditions, E. coli O157:H7 is not pathogenic in weaned calves, and while it does not appear to colonize mucosal surfaces for extended periods, E. coli O157:H7 persists in the contents of the rumen and colon as a source for fecal shedding.",,"['Brown, C A', 'Harmon, B G', 'Zhao, T', 'Doyle, M P']",,,,
,PMC,"Genetic and amino acid analysis of the GL protein of Canadian, American and European equine arteritis virus isolates.",,PMC1189375,,,"The genetic variation in equine arteritis virus (EAV) GL protein encoding gene was investigated. Nucleic and deduced amino acid sequences from 7 different EAV isolates, including 4 eastern Canadian field isolates, were compared with those of the Bucyrus reference strain. Nucleotide sequence identities between these isolates and the Bucyrus reference strain ranged from 87.5% (Vienna isolate) to 93.9% (11958 isolate). Amino acid identities with the Bucyrus reference strain varied from 90.2% (Vienna isolate) to 95.1% (19933 isolate). A 2nd potential N-linked glycosylation site was found at position 81 in the GL protein of all EAV isolates. Three amino acid substitutions at residue position 90 (Glu-->Val), position 101 (Ala-->Val or Thr), and position 119 (Val-->Leu, Phe or Ser) were also found in all EAV isolates. Phylogenetic analysis showed that the North American EAV isolates, including the Canadian isolates, and the European prototype Vienna isolate could be classified in 2 distinct groups. Three putative sequential antigenic sites were predicted in EAV GL protein. The 1st antigenic site (TAQRFT) was located at positions 24 to 29, and the 2nd antigenic site (RYDEHTA) at positions 47 to 53. The 3rd antigenic site was predicted to be located at positions 78 to 84 and showed the less conserved amino acid sequence.",,"['St-Laurent, G', 'Lepage, N', 'Carman, S', 'Archambault, D']",,,,
,PMC,"Effect of glutamine or glycine containing oral electrolyte solutions on mucosal morphology, clinical and biochemical findings, in calves with viral induced diarrhea.",,PMC1189368,,,"Twenty-one diarrheic calves were randomly assigned to 1 of 3 oral electrolyte treatments. The treatments were either a conventional oral electrolyte containing glycine (40 mmol/L) as the amino acid, an oral electrolyte in which glutamine (40 mmol/L) replaced glycine or an electrolyte in which high concentrations of glutamine (400 mmol/L) replaced glycine. The calves were monitored while on trial and at the end of the treatment they were euthanized and a necropsy was immediately performed. Calves fed the high glutamine electrolyte had more treatment failures (2/7 versus 0/7 for each of the other 2 treatments). There was a significant effect of type of electrolyte on fecal consistency. Calves fed the glycine containing electrolyte had the most solid feces. Duodenal villus height was significantly affected by the type of electrolyte: values (mean +/- 1 SEM) were 0.61 +/- 0.09, 0.46 +/- 0.05, and 0.59 +/- 0.07 mm for high glutamine, low glutamine and glycine electrolytes respectively. There was no significant difference in small intestinal surface area between groups. High glutamine treated calves had the greatest capacity to absorb xylose from the small intestine but this difference was not statistically significant. Overall, this trial does not suggest that substituting glutamine for glycine in oral electrolyte solutions improves treatment of diarrheic calves or speeds mucosal healing.",,"['Naylor, J M', 'Leibel, T', 'Middleton, D M']",,,,
,PMC,"Parameters of disease progression in long-term experimental feline retrovirus (feline immunodeficiency virus and feline leukemia virus) infections: hematology, clinical chemistry, and lymphocyte subsets.",,PMC170472,,,"After several years of latency, feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) cause fatal disease in the cat. The aim of this study was to determine laboratory parameters characteristic of disease progression which would allow a better description of the asymptomatic phase and a better understanding of the pathogenesis of the two infections. Therefore, experimentally infected cats (FIV and/or FeLV positive) and control animals were observed over a period of 6.5 years under identical conditions. Blood samples were analyzed for the following: complete hematology, clinical chemistry, serum protein electrophoresis, and determination of CD4+ and CD8+ lymphocyte subsets. The following hematological and clinical chemistry parameters were markedly changed in the FIV-infected animals from month 9 onwards: glucose, serum protein, gamma globulins, sodium, urea, phosphorus, lipase, cholesterol, and triglyceride. In FeLV infection, the markedly changed parameters were mean corpuscular volume, mean corpuscular hemoglobin, aspartate aminotransferase, and urea. In contrast to reports of field studies, neither FIV-positive nor FeLV-positive animals developed persistent leukopenia, lymphopenia, or neutropenia. A significant decrease was found in the CD4+/CD8+ ratio in FIV-positive and FIV-FeLV-positive animals mainly due to loss of CD4+ lymphocytes. In FeLV-positive cats, both CD4+ and, to a lesser degree, CD8+ lymphocytes were decreased in long-term infection. The changes in FIV infection may reflect subclinical kidney dysfunction, changes in energy and lipid metabolism, and transient activation of the humoral immune response as described for human immunodeficiency virus (HIV) infections. The changes in FeLV infection may also reflect subclinical kidney dysfunction and, in addition, changes in erythrocyte and immune function of the animals. No severe clinical signs were observed in the FIV-positive cats, while FeLV had a severe influence on the life expectancy of persistently positive cats. In conclusion, several parameters of clinical chemistry and hematology were changed in FIV and FeLV infection. Monitoring of these parameters may prove useful for the evaluation of candidate FIV vaccines and antiretroviral drugs in cats. The many parallels between laboratory parameters in FIV and HIV infection further support the importance of FIV as a model for HIV.",,"['Hofmann-Lehmann, R', 'Holznagel, E', 'Ossent, P', 'Lutz, H']",,,,
,PMC,Activation of intestinal intraepithelial T lymphocytes in calves infected with Cryptosporidium parvum.,,PMC174574,,,"The objective of this study was to identify disease-related changes in lymphocyte populations within ileal mucosae of calves with cryptosporidiosis. Groups of five neonatal calves were orally infected at 3 days of age with 10(8) oocysts and maintained in enteric-pathogen-free conditions until clinical disease was established or until the animals had recovered from disease. Age-matched uninfected calves were used for comparison. Ileal mucosal lymphocytes were collected, quantitated, and phenotyped to determine whether changes in lymphocyte composition occurred in infected animals. We observed significantly larger numbers of intraepithelial CD8+ T lymphocytes in ileal mucosae from acutely infected calves compared with those from control animals. In addition, a proportion of intraepithelial CD4+ T cells from acutely infected calves coexpressed CD25, whereas there was an absence of coexpressed CD25 on CD4+ T cells from control calves. Ex vivo reverse transcriptase PCR of RNA from intraepithelial lymphocytes from control calves showed a cytokine expression pattern consisting of tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma), while intraepithelial lymphocytes from calves with cryptosporidiosis expressed IFN-gamma but not TNF-alpha. Together, the results indicate that changes occur in the ileal intraepithelial lymphocyte population coincidently with Cryptosporidium parvum-induced enteric disease.",,"['Wyatt, C R', 'Brackett, E J', 'Perryman, L E', 'Rice-Ficht, A C', 'Brown, W C', ""O'Rourke, K I""]",,,,
,PMC,Characterization of monoclonal antibodies to the hemagglutinin-esterase glycoprotein of a bovine coronavirus associated with winter dysentery and cross-reactivity to field isolates.,,PMC229508,,,"Seven hybridoma cell lines producing monoclonal antibodies (MAbs) to the hemagglutinin-esterase (HE) glycoprotein of bovine coronavirus (BCV) were obtained from BALB/c mice that were immunized with an enriched peplomeric fraction of the winter dysentery (WD)-associated strain BCQ.2590. The specificities of these MAbs to either the dimeric (140-kDa) or the monomeric (65-kDa) form of the HE glycoprotein were determined by Western immunoblotting experiments with purified virus and immunoprecipitation tests with [35S]methionine-labelled infected cell extracts. Four of these anti-HE MAbs inhibited the hemagglutinating activity of the virus and three weakly neutralized its infectivity in vitro. In addition, competition binding assays allowed for the definition of two independent antigenic domains (domains A and D) and two overlapping antigenic domains (domains B and C) for the HE glycoprotein of the WD-associated strain; epitopes located within antigenic domain A were not associated with hemagglutination inhibition (HAI) and virus neutralization activities. In HAI tests, the four anti-HA MAbs defined two distinct antigenic subgroups among 24 BCV field isolates that have been associated with either typical outbreaks of WD or neonatal calf diarrhea (NCD) in Quebec dairy herds from 1986 to 1996. The Quebec WD-associated strains of BCV, as well as some of the NCD-associated strains isolated since 1991, fell within a subgroup distinct from that of the prototype Mebus strain.",,"['Milane, G', 'Kourtesis, A B', 'Dea, S']",,,,
,PMC,Murine coronavirus packaging signal confers packaging to nonviral RNA.,,PMC191125,,,"Studies of defective interfering (DI) RNAs of the murine coronavirus mouse hepatitis virus (MHV) suggest that a 69-nucleotide-long packaging signal is necessary for MHV genomic RNA packaging into MHV particles. In this study we showed that when RNA transcripts that consisted of a non-MHV sequence and the packaging signal were expressed in MHV-infected cells, they were packaged into MHV particles. Those RNA transcripts that lacked the packaging signal or those containing a mutated packaging signal did not package efficiently. Thus, the presence of the packaging signal was sufficient for RNA packaging into MHV particles.",,"['Woo, K', 'Joo, M', 'Narayanan, K', 'Kim, K H', 'Makino, S']",,,,
,PMC,Infection of primary cultures of human neural cells by human coronaviruses 229E and OC43.,,PMC191121,,,"We evaluated the ability of human coronaviruses to infect primary cultures of human neural cells. Double immunofluorescence with antibodies to virus and cell markers showed infection of fetal astrocytes and of adult microglia and astrocytes by strain OC43. RNA amplification revealed infection of fetal astrocytes, adult microglia, and a mixed culture of adult oligodendrocytes and astrocytes by strain 229E. Infectious virus was released only from fetal astrocytes, with higher titers for OC43. Human coronaviruses have the capacity to infect some cells of the central nervous system, although infection of adult cells appears abortive.",,"['Bonavia, A', 'Arbour, N', 'Yong, V W', 'Talbot, P J']",,,,
,PMC,A sorting motif localizes the foamy virus glycoprotein to the endoplasmic reticulum.,,PMC191117,,,"We recently identified an endoplasmic reticulum (ER) retrieval signal-the dilysine motif-in the glycoproteins of all five foamy viruses (FVs) for which sequences were available (P. A. Goepfert, G. Wang, and M. J. Mulligan, Cell 82:543-544, 1995). In the present study, expression of recombinant human FV (HFV) glycoprotein and analyses of oligosaccharide modifications and precursor cleavage indicated that the protein was localized to the ER. HFV glycoproteins encoding seven different dilysine motif mutations were then expressed. The results indicated that disruptions of the dilysine motif resulted in higher levels of forward transport of the HFV glycoprotein from the ER through the Golgi apparatus to the plasma membrane. We conclude that the dilysine motif is responsible for ER sorting of the FV glycoprotein. Signal-mediated ER localization has not previously been described for a retroviral glycoprotein.",,"['Goepfert, P A', 'Shaw, K L', 'Ritter, G D', 'Mulligan, M J']",,,,
,PMC,"Interspecies aminopeptidase-N chimeras reveal species-specific receptor recognition by canine coronavirus, feline infectious peritonitis virus, and transmissible gastroenteritis virus.",,PMC191108,,,"We report that cells refractory to canine coronavirus (CCV) and feline infectious peritonitis virus (FIPV) became susceptible when transfected with a chimeric aminopeptidase-N (APN) cDNA containing a canine domain between residues 643 and 841. This finding shows that APN recognition by these viruses is species related and associated with this C-terminal domain. The human/canine APN chimera was also able to confer susceptibility to the porcine transmissible gastroenteritis virus (TGEV), whereas its human/porcine homolog failed to confer susceptibility to CCV and FIPV. A good correlation was observed between the capacity of CCV, FIPV, and TGEV to recognize the different interspecies APN chimeras and their ability to infect cells derived from the relevant species. As an exception, TGEV was found to use a human/bovine APN chimera as a receptor although itself unable to replicate in bovine cells.",,"['Benbacer, L', 'Kut, E', 'Besnardeau, L', 'Laude, H', 'Delmas, B']",,,,
,PMC,Processing of a cellular polypeptide by 3CD proteinase is required for poliovirus ribonucleoprotein complex formation.,,PMC191087,,,"Poliovirus interactions with host cells were investigated by studying the formation of ribonucleoprotein complexes at the 3' end of poliovirus negative-strand RNA which are presumed to be involved in viral RNA synthesis. It was previously shown that two host cell proteins with molecular masses of 36 and 38 kDa bind to the 3' end of viral negative-strand RNA at approximately 3 to 4 h after infection. We tested the hypothesis that preexisting cellular proteins are modified during the course of infection and are subsequently recruited to play a role in viral replication. It was demonstrated that the 38-kDa protein, either directly or indirectly, is the product of processing by poliovirus 3CD/3C proteinase. Only the modified 38-kDa protein, not its precursor protein, has a high affinity for binding to the 3' end of viral negative-strand RNA. This modification depends on proteolytically active proteinase, and a direct correlation between the levels of 3CD proteinase and the 38-kDa protein was demonstrated in infected tissue culture cells. The nucleotide (nt) 5-10 region (positive-strand numbers) of poliovirus negative-strand RNA is important for binding of the 38-kDa protein. Deletion of the nt 5-10 region in full-length, positive-strand RNA renders the RNA noninfectious in transfection experiments. These results suggest that poliovirus 3CD/3C proteinase processes a cellular protein which then plays an essential role during the viral life cycle.",,"['Roehl, H H', 'Parsley, T B', 'Ho, T V', 'Semler, B L']",,,,
,PMC,Mouse hepatitis virus is cleared from the central nervous systems of mice lacking perforin-mediated cytolysis.,,PMC191062,,,"Perforin-deficient [perforin (-/-)] mice were infected with two strains of JHM virus (JHMV) to analyze the role of perforin-mediated cytotoxicity in acute lethal and subacute central nervous system (CNS) infections. During both acute and subacute infections, the overall mortality of the perforin (-/-) mice was not different from that of the controls. Perforin (-/-) mice survived longer than the controls, consistent with reduced morbidity. Both strains of virus were cleared from the perforin (-/-) mice as in the controls; however, the rate of clearance was delayed in the perforin (-/-) mice, indicating that perforin-mediated cytolysis is involved in viral clearance. The absence of perforin-mediated cytolysis did not prevent encephalomyelitis or extensive demyelination. Cells undergoing apoptosis were detected in the CNS of both the perforin (-/-) and control groups, indicating that perforin is not essential for programmed cell death. Neutralizing antibodies were not detected in either group of mice until day 9 postinfection, when the majority of the virus had been cleared. These data further confirm the importance of cell-mediated cytotoxicity and suggest that additional components of the immune response contribute to the clearance of JHMV from the CNS.",,"['Lin, M T', 'Stohlman, S A', 'Hinton, D R']",,,,
,PMC,Preformed cytoplasmic nucleocapsids are not necessary for alphavirus budding.,,PMC452474,,,"According to the present model for assembly of alphaviruses, e.g. Semliki Forest virus (SFV), the viral genome is first encapsidated into a nucleocapsid (NC) in cytoplasm and this is then used for budding at plasma membrane (PM). The preformed NC is thought to act as a template on which the viral envelope can be organized. In the present work we have characterized two SFV deletion mutants which did not assemble NCs in the cytoplasm but which instead appeared to form NCs at the PM simultaneously with virus budding. The deletions were introduced in a conserved 14 residue long linker peptide that joins the amino-terminal RNA-binding domain with the carboxy-terminal serine-protease domain of the capsid protein. Despite the deletions and the change in morphogenesis, wild-type (wt)-like particles were produced with almost wt efficiency. It is suggested that the NC assembly defect of the mutants is rescued through spike-capsid interactions at PM. The results show that the preassembly of NCs in the cytoplasm is not a prerequisite for alphavirus budding. The apparent similarities of the morphogenesis pathways of wt and mutant SFV with those of type D and type C retroviruses are discussed.",,"['Forsell, K', 'Griffiths, G', 'Garoff, H']",,,,
,PMC,Investigation of chronic diarrhoea in acquired immunodeficiency syndrome. A prospective study of 155 patients.,,PMC1383454,,,"BACKGROUND AND AIMS: The optimum diagnostic investigation for patients with acquired immunodeficiency syndrome (AIDS) and diarrhoea is not known. Often no pathogen is detected and it is unclear whether this is because pathogens are absent in some patients or the investigations used fail to detect them. The hypothesis that AIDS related diarrhoea is usually due to an infection, which can be identified by a simple diagnostic strategy based on the results of intensive investigation of a cohort of such patients, was investigated. METHODS: 155 patients with AIDS and chronic diarrhoea underwent contemporaneous examination of stools, duodenal, jejunal, and rectal biopsy specimens and duodenal aspirate for bacterial, protozoal, and viral pathogens. A decision tree analysis was used to determine the best sequential diagnostic strategy for clinicians. RESULTS: 128 of 155 patients investigated (83%) had at least one potential pathogen. The presenting clinical features could not predict the presence or site of the pathogens. Stool analysis identified the most pathogens (93 of 199, 47%). Rectal biopsy was essential for the diagnosis of cytomegalovirus and adenovirus. Duodenal biopsy was as helpful as jejunal biopsy and detected some treatable pathogens missed by other methods. Electron microscopy, impression smears, and duodenal aspirate yielded little extra information. If gut biopsy was reserved for patients without a stool pathogen, some treatable pathogens would have been missed. CONCLUSION: Most patients with AIDS and chronic diarrhoea have at least one gut pathogen, which can be identified by stool analysis and light microscopic examination of duodenal and rectal biopsies. Some pathogens will be missed unless all these investigations are done on all such patients.",,"['Blanshard, C', 'Francis, N', 'Gazzard, B G']",,,,
,PMC,Two related strains of feline infectious peritonitis virus isolated from immunocompromised cats infected with a feline enteric coronavirus.,,PMC229479,,,"Two groups of cats were experimentally infected orally with the cat-passaged RM strain of feline enteric coronavirus (FECV-RM). One group of cats (n = 19) had been chronically infected with feline immunodeficiency virus (FIV) for over 6 years, while a second control group (n = 20) consisted of FIV-naive siblings. Fecal virus shedding of FECV occurred in both groups starting on day 3 postinfection, nearly ceased by 4 weeks in FIV-uninfected cats, but remained at high levels in FIV-infected animals. FIV-infected cats shed virus for a longer period of time and at levels 10 to 100 times greater than those for FIV-uninfected cats. The coronavirus antibody response of the FIV-infected cats was delayed and of reduced titer compared with that of the FIV-uninfected animals. Cats in both groups remained asymptomatic for the first two months following FECV-RM infection; however, 8 to 10 weeks postinfection two cats in the FIV-infected group developed feline infectious peritonitis (FIP). The FIP viruses (designated FIPV-UCD9 and -UCD10) isolated from these two cats had almost complete genetic homology to each other and to the infecting FECV-RM. However, unlike FECV-RM, they readily induced FIP when inoculated intraperitoneally into specific-pathogen-free cats. This study confirms that FIPVs are frequently and rapidly arising mutants of FECV. Immunosuppression caused by chronic FIV infection may have enhanced the creation and selection of FIPV mutants by increasing the rate of FECV replication in the bowel and inhibiting the host's ability to combat the mutant viruses once they occurred.",,"['Poland, A M', 'Vennema, H', 'Foley, J E', 'Pedersen, N C']",,,,
,PMC,Surveillance of community-acquired viral infections due to respiratory viruses in Rhone-Alpes (France) during winter 1994 to 1995.,,PMC229450,,,"Nasal swab from patients with acute flu-like illness were evaluated for the presence of respiratory viruses in the Rhone-Alpes region of France from 1 October 1994 through 2 May 1995. The relative frequencies and seasonal distributions of the specific viruses were assessed. In addition, virus type was correlated with specific clinical signs and symptoms. During the study, 962 samples were collected by 75 medical practitioners participating in the Groupe Regional d'Observation de la Grippe surveillance network. One or more viruses were detected from 348 samples (36.1%), including 108 respiratory syncytial virus (RSV), 64 influenza virus A type H3N2, 47 influenza virus B, 64 coronavirus, 35 rhinovirus, 22 adenovirus, 5 enterovirus, and 3 parainfluenza-fluenza strains. There were 16 mixed infections. RSV infections peaked in the early winter, and influenza viruses A and B infections peaked during the late winter and early spring. There were two peaks of coronavirus infections (late fall and late winter). Other viruses were detected at lower levels throughout the study period. Patients from whom adenovirus was isolated were significantly more likely to have a fever of > 39.5 degrees C than were patients with other detectable viruses (P < 0.001). Furthermore, there was a significant correlation between influenza and cough (P < 0.01) and RSV and bronchiolitis (P < .001). Thus, the current study defined the overall and relative frequencies of respiratory virus detection from nasal swab specimens in patients with an acute flu-like illness in the Rhone-Alpes region of France during a 7-month period. Correlation with clinical signs and symptoms and provisional conclusions regarding seasonality were also determined.",,"['Lina, B', 'Valette, M', 'Foray, S', 'Luciani, J', 'Stagnara, J', 'See, D M', 'Aymard, M']",,,,
,PMC,Apoptosis and T-cell depletion during feline infectious peritonitis.,,PMC190995,,,"Cats that have succumbed to feline infectious peritonitis, an immune-mediated disease caused by variants of feline coronaviruses, show apoptosis and T-cell depletion in their lymphoid organs. The ascitic fluid that develops in the course of the condition causes apoptosis in vitro but only in activated T cells. Since feline infectious peritonitis virus does not infect T cells, and viral proteins did not inhibit T-cell proliferation, we postulate that soluble mediators released during the infection cause apoptosis and T-cell depletion.",,"['Haagmans, B L', 'Egberink, H F', 'Horzinek, M C']",,,,
,PMC,"Feline aminopeptidase N serves as a receptor for feline, canine, porcine, and human coronaviruses in serogroup I.",,PMC190961,,,"Two members of coronavirus serogroup I, human respiratory coronavirus HCV-229E and porcine transmissible gastroenteritis virus (TGEV), use aminopeptidase N (APN) as their cellular receptors. These viruses show marked species specificity in receptor utilization, as HCV-229E can utilize human but not porcine APN, while TGEV can utilize porcine but not human APN. To determine whether feline APN could serve as a receptor for two feline coronaviruses in serogroup I, feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FeCV), we cloned the cDNA encoding feline APN (fAPN) by PCR from cDNA isolated from a feline cell line and stably expressed it in FIPV- and FeCV-resistant mouse and hamster cells. The predicted amino acid sequence of fAPN shows 78 and 77% identity with human and porcine APN, respectively. When inoculated with either of two biologically different strains of FIPV or with FeCV, fAPN-transfected mouse and hamster cells became infected and viral antigens developed in the cytoplasm. Infectious FIPV was released from hamster cells stably transfected with fAPN. The fAPN-transfected mouse and hamster cells were challenged with other coronaviruses in serogroup I including canine coronavirus, porcine coronavirus TGEV, and human coronavirus HCV-229E. In addition to serving as a receptor for the feline coronaviruses, fAPN also served as a functional receptor for each of these serogroup I coronaviruses as shown by development of viral antigens in the cytoplasm of infected mouse or hamster cells stably transfected with fAPN. In contrast, fAPN did not serve as a functional receptor for mouse hepatitis virus (MHV-A59), which is in serogroup II and utilizes mouse biliary glycoprotein receptors unrelated to APN. Thus, fAPN serves as a receptor for a much broader range of group I coronaviruses than human and porcine APNs. The human, porcine, and canine coronaviruses in serogroup I that are able to use fAPN as a receptor have previously been shown to infect cats without causing disease. Therefore, host factors in addition to receptor specificity apparently affect the virulence and transmissibility of nonfeline serogroup I coronaviruses in the cat.",,"['Tresnan, D B', 'Levis, R', 'Holmes, K V']",,,,
,PMC,Replication and packaging of coronavirus infectious bronchitis virus defective RNAs lacking a long open reading frame.,,PMC190960,,,"The construction of a full-length clone of the avian coronavirus infectious bronchitis virus (IBV) defective RNA (D-RNA), CD-91 (9,080 nucleotides [Z. Penzes et al., Virology 203:286-293]), downstream of the bacteriophage T7 promoter is described. Electroporation of in vitro T7-transcribed CD-91 RNA into IBV helper virus-infected primary chick kidney cells resulted in the production of CD-91 RNA as a replicating D-RNA in subsequent passages. Three CD-91 deletion mutants were constructed--CD-44, CD-58, and CD-61--in which 4,639, 3,236, and 2,953 nucleotides, respectively, were removed from CD-91, resulting in the truncation of the CD-91 long open reading frame (ORF) from 6,465 to 1,311, 1,263, or 2,997 nucleotides in CD-44, CD-58, or CD-61, respectively. Electroporation of in vitro T7-transcribed RNA from the three constructs into IBV helper virus-infected cells resulted in the replication and packaging of CD-58 and CD-61 but not CD-44 RNA. The ORF of CD-61 was further truncated by the insertion of stop codons into the CD-61 sequence by PCR mutagenesis, resulting in constructs CD-61T11 (ORF: nucleotides 996 to 1,058, encoding 20 amino acids), CD-61T22 (ORF: nucleotides 996 to 2,294, encoding 432 amino acids), and CD-61T24 (ORF: nucleotides 996 to 2,450, encoding 484 amino acids), all of which were replicated and packaged to the same levels as observed for either CD-61 or CD-91. Analysis of the D-RNAs showed that the CD-91- or CD-61-specific long ORFs had not been restored. Our data indicate that IBV D-RNAs based on the natural D-RNA, CD-91, do not require a long ORF for efficient replication. In addition, a 1.4-kb sequence, corresponding to IBV sequence at the 5' end of the 1b gene, may be involved in the packaging of IBV D-RNAs or form part of a cis-acting replication element.",,"['Pénzes, Z', 'Wroe, C', 'Brown, T D', 'Britton, P', 'Cavanagh, D']",,,,
,PMC,An IkappaB homolog encoded by African swine fever virus provides a novel mechanism for downregulation of proinflammatory cytokine responses in host macrophages.,,PMC190944,,,"Cytokines stimulate inflammatory defenses against viral infections. In order to evade host defenses, viruses have developed strategies to counteract antiviral cytokines. African swine fever virus (ASFV) is a large, double-stranded DNA virus that infects macrophages. This study demonstrates that ASFV effectively inhibited phorbol myristic acid-induced synthesis of antiviral, proinflammatory cytokines alpha interferon, tumor necrosis factor alpha, and interleukin-8 in infected macrophages as assessed by enzyme-linked immunosorbent assay and reverse transcriptase PCR. In contrast, levels of mRNA and protein for transforming growth factor beta, an anti-inflammatory cytokine, were increased by ASFV infection, suggesting that ASFV-induced inhibition of cytokine synthesis may be limited to cytokines activated by NFkappaB. An interleukin-8 promoter, containing an NFkappaB enhancer site, driving expression of a luciferase reporter gene was used to show that NFkappaB-dependent transcription was inhibited by the virus and by a cloned ASFV gene, A238L. This gene encodes a protein with homology to IkappaB, the inhibitor of NFkappaB. Electrophoretic mobility shift assay showed that cells expressing the A238L gene inhibited NFkappaB binding to DNA. These results suggest that the A238L gene product interacts with NFkappaB to prevent transcription and downregulate proinflammatory cytokine production. This novel viral evasion strategy encoded in a single IkappaB-like protein may be capable of inhibiting most macrophage NFkappaB-dependent antiviral mechanisms and may provide insights into how ASFV causes a fatal hemorrhagic disease of domestic pigs and a persistent infection in the African warthog, which is its natural permissive host.",,"['Powell, P P', 'Dixon, L K', 'Parkhouse, R M']",,,,
,PMC,Involvement of the endoplasmic reticulum in the assembly and envelopment of African swine fever virus.,,PMC190927,,,"African swine fever (ASF) virus is a large enveloped DNA virus assembled in the cytoplasm of cells. In this study, the membrane compartments involved in the envelopment of ASF virus were investigated. A monoclonal antibody recognizing p73, the major structural protein of ASF virus, was generated to analyze the binding of p73 to membranes during the assembly of the virus. Approximately 50% of the intracellular pool of p73 associated with membranes as a peripheral membrane protein. Binding was rapid and complete within 15 min of synthesis. Subcellular membrane fractionation showed that newly synthesized p73 molecules cosedimented with endoplasmic reticulum (ER) membranes and remained associated with the ER during a 2-h chase. A similar distribution on gradients was recorded for p17, a structural membrane protein of ASF virus. The results suggested that the ER was involved in the assembly of ASF virus. A protease protection assay demonstrated a time-dependent envelopment of the membrane bound, but not cytosolic, pool of p73. Envelopment of p73 took place 1 h after binding to membranes and was completed 1 h before the first detection of p73 in virions secreted from cells. Envelopment was unaffected by brefeldin A and monensin, drugs that block membrane transport between the ER and Golgi. Taken together the results provide evidence for the binding of ASF virus structural proteins to a specific membrane compartment and implicate a role for the ER in the assembly and envelopment of ASF virus.",,"['Cobbold, C', 'Whittle, J T', 'Wileman, T']",,,,
,PMC,Interaction of measles virus glycoproteins with the surface of  uninfected peripheral blood lymphocytes induces immunosuppression  in vitro,,PMC24069,,,"A marked suppression of immune function has long been recognized as a major cause of the high morbidity and mortality rate associated with acute measles. As a hallmark of measles virus (MV)-induced immunosuppression, peripheral blood lymphocytes (PBLs) isolated from patients exhibit a significantly reduced capacity to proliferate in response to mitogens, allogens, or recall antigens. In an in vitro system we show that proliferation of naive PBLs [responder cells (RCs)] in response to a variety of stimuli was significantly impaired after cocultivation with MV-infected, UV-irradiated autologous PBLs [presenter cells (PCs)]. We further observed that a 50% reduction in proliferation of RCs could still be observed when the ratio of PC to RC was 1:100. The effect was completely abolished after physical separation of the two populations, which suggests that soluble factors were not involved. Proliferative inhibition of the RCs was observed after short cocultivation with MV-infected cells, which indicates that surface contact between one or more viral proteins and the RC population was required. We identified that the complex of both MV glycoproteins, F and H, is critically involved in triggering MV-induced suppression of mitogen-dependent proliferation, since the effect was not observed (i) using a recombinant MV in which F and H were replaced with vesicular stomatitis virus G or (ii) when either of these proteins was expressed alone. Coexpression of F and H, however, lead to a significant proliferative inhibition in the RC population. Our data indicate that a small number of MV-infected PBLs can induce a general nonresponsiveness in uninfected PBLs by surface contact, which may, in turn, account for the general suppression of immune responses observed in patients with acute measles.",,"['Schlender, Jörg', 'Schnorr, Jens-Jörg', 'Spielhofer, Pius', 'Cathomen, Toni', 'Cattaneo, Roberto', 'Billeter, Martin\u2009A.', 'ter\u2009Meulen, Volker', 'Schneider-Schaulies, Sibylle']",,,,
,PMC,Pristane-induced arthritis in rats: a new model for rheumatoid arthritis with a chronic disease course influenced by both major histocompatibility complex and non-major histocompatibility complex genes.,,PMC1865278,,,"We present a novel animal model for rheumatoid arthritis induced with a well defined synthetic adjuvant oil, pristane. Two weeks after a single intradermal injection of 150 microliters of pristane, the rats developed severe and chronic arthritis. The inflammation was restricted to the joints and involved pannus formation, major histocompatibility complex (MHC) class II expression, and T lymphocyte infiltration. The initial development as well as the chronic stage of pristane-induced arthritis was ameliorated by treatment with antibodies to the alpha beta-T-cell receptor showing that the disease is T cell dependent. Increased levels of interleukin in serum was seen after pristane injection but not during the chronic stage of arthritis. Joint erosions were accompanied by elevated serum levels of cartilage oligomeric matrix protein. Comparison of MHC congenic LEW strains showed that the severity and chronicity of arthritis varied among the different MHC haplotypes. Rats with RT1f haplotype showed a significantly higher susceptibility to pristane-induced arthritis. A strong influence of non-MHC genes was also suggested by the variability of arthritis susceptibility among different strains with the same MHC haplotype; the most susceptible background was the DA and the least susceptible was the E3. Arthritis induced with a well defined nonimmunogenic adjuvant, with a disease course that closely resembles that of rheumatoid arthritis, makes a suitable animal model for future studies of the pathology and genetics of rheumatoid arthritis.",,"['Vingsbo, C.', 'Sahlstrand, P.', 'Brun, J. G.', 'Jonsson, R.', 'Saxne, T.', 'Holmdahl, R.']",,,,
,PMC,Induction of the membrane alanyl aminopeptidase gene and surface expression in human T-cells by mitogenic activation.,,PMC1217861,,,"The metal-dependent membrane alanyl aminopeptidase (amino-peptidase N, APN, CD13; EC 3.4.11.2) is a well-established marker of normal and malignant cells of the myelo-monocytic lineage. It is also expressed by leukaemic blasts of a small group of patients suffering from acute or chronic lymphoid leukaemia. CD13-specific monoclonal antibodies do not bind to the surface of normal B lymphocytes, and APN mRNA was not detectable by Northern analysis in normal lymphocytes or in T-cell lines. Recently the expression of the APN gene in T-cell lines as well as the ability of these cells to cleave chromogenic substrates preferred by APN have been demonstrated [Lendeckel, Wex, Kähne, Frank, Reinhold and Ansorge (1994) Cell. Immunol. 153, 214-226]. Here, by means of dot-blot hybridization and RNase protection assay, evidence is provided that human peripheral T-cells as well as derived cell lines contain significant amounts of APN mRNA, comparable to that in the promyeloic cell line U937, and that mitogenic activation of peripheral human T-cells leads to a more than 4-fold increase in their APN mRNA content. In the course of activation, T-cells increase their total alanine p-nitroanilide-hydrolysing activity to approx. 7-fold that of resting cells. Furthermore these cells become immunoreactive towards CD13 to a significant extent (up to 51%) as shown by surface staining and confirmed by activity staining and immunostaining after isoelectric focusing (pI of T-cell APN = 4.6). In addition it is demonstrated by fluorescence microscopy that viable, activated T-cells effectively cleave the fluorogenic aminopeptidase substrate bis-glycyl-rhodamine 110 and that the corresponding aminopeptidase activity is associated with the cell surface. We show that specific inhibitors of APN, probestin and actinonin, strongly decrease DNA synthesis in phytohaemagglutinin (PHA)-stimulated T-cells. In summary, evidence is presented that in the course of mitogenic activation human peripheral T-cells increase the expression of APN both at the transcriptional level and at the cell surface. This has been demonstrated both at the APN mRNA level and at the protein level with respect to aminopeptidase enzymic activity and CD13 immunoreactivity.",,"['Lendeckel, U', 'Wex, T', 'Reinhold, D', 'Kähne, T', 'Frank, K', 'Faust, J', 'Neubert, K', 'Ansorge, S']",,,,
,PMC,Chronic fibrinous and necrotic orchitis in a cat.,,PMC1576509,,,,,"['Foster, R A', 'Caswell, J L', 'Rinkardt, N']",,,,
,PMC,Polycistronic (tri- or bicistronic) phytoreoviral segments translatable in both plant and insect cells.,,PMC190894,,,"Genomic segment S12 of rice dwarf virus and segment S9 of wound tumor virus, both members of the genus Phytoreovirus, have small out-of-phase overlapping open reading frames (ORFs). Western blot (immunoblot) analysis revealed that rice dwarf virus S12 mRNA specified translation products from the large ORF and two overlapping small ORFs both in rice plant hosts and in Spodoptera frugiperda insect cells. These results provide the first example of a tricistronic mRNA for a segmented double-stranded RNA virus. Similarly, wound tumor virus S9 mRNA was found to direct the synthesis of protein products from both the large ORF and small out-of-frame ORF in S. frugiperda cells. Results of site-specific and deletion mutagenesis studies were consistent with a leaky scanning translation mechanism for the synthesis of the small ORFs.",,"['Suzuki, N', 'Sugawara, M', 'Nuss, D L', 'Matsuura, Y']",,,,
,PMC,Structural requirements for low-pH-induced rearrangements in the envelope glycoprotein of tick-borne encephalitis virus.,,PMC190891,,,"The exposure of the flavivirus tick-borne encephalitis (TBE) virus to an acidic pH is necessary for virus-induced membrane fusion and leads to a quantitative and irreversible conversion of the envelope protein E dimers to trimers. To study the structural requirements for this oligomeric rearrangement, the effect of low-pH treatment on the oligomeric state of different isolated forms of protein E was investigated. Full-length E dimers obtained by solubilization of virus with the detergent Triton X-100 formed trimers at low pH, whereas truncated E dimers lacking the stem-anchor region underwent a reversible dissociation into monomers without forming trimers. These data suggest that the low-pH-induced rearrangement in virions is a two-step process involving a reversible dissociation of the E dimers followed by an irreversible formation of trimers, a process which requires the stem-anchor portion of the protein. This region contains potential amphipathic alpha-helical and conserved structural elements whose interactions may contribute to the rearrangements which initiate the fusion process.",,"['Stiasny, K', 'Allison, S L', 'Marchler-Bauer, A', 'Kunz, C', 'Heinz, F X']",,,,
,PMC,A primary production deficit in the thrombocytopenia of equine infectious anemia.,,PMC190855,,,"The purpose of this study was to identify the mechanisms responsible for the thrombocytopenia that develops following infection of horses by the lentivirus equine infectious anemia virus (EIAV). Immunocompetent Arabian foals and Arabian foals with severe combined immunodeficiency (SCID), which lack functional B and T lymphocytes, were experimentally infected with EIAV. Levels of viremia and a number of clinical and hematologic parameters were examined prior to and following infection. Thrombocytopenia was not dependent on the immune response: SCID foals were affected as severely as immunocompetent foals. Production of platelets, measured by metabolic incorporation of radioactive label, was significantly reduced. The decrease ranged from 35 to 89% in three SCID and two immunocompetent foals examined. Platelet survival, measured by 51Cr labeling, also declined following infection in both SCID and immunocompetent foals: 51 and 68%, respectively, relative to the preinfection life spans. The difference between immunocompetent and immunodeficient foals was not statistically significant. The number of megakaryocytes (MK) per square millimeter of bone marrow, determined by digitizing morphometry, was not significantly altered in either SCID or immunocompetent thrombocytopenic foals. Numbers of denuded MK nuclei per unit area increased, but the elevation was not statistically significant. No evidence for viral replication in MK was found. Three different parameters of intravascular coagulation (activated prothombin time, fibrin degradation products, and one-step prothombin time) remained normal until after platelet numbers had declined significantly, arguing against an important role for disseminated intravascular coagulation. The findings indicate that EIAV induces thrombocytopenia principally through an indirect, noncytocidal suppressive effect on platelet production, the mechanism of which is unknown. A shortening of platelet life span apparently contributes moderately to the platelet deficit as well. The shortening of platelet life span is multifactorial in origin, including both mechanisms that depend on an active immune response and those that do not.",,"['Crawford, T B', 'Wardrop, K J', 'Tornquist, S J', 'Reilich, E', 'Meyers, K M', 'McGuire, T C']",,,,
,PMC,Inducible expression of the vaccinia virus A17L gene provides a synchronized system to monitor sorting of viral proteins during morphogenesis.,,PMC190833,,,"The vaccinia virus (VV) A17L gene encodes a 21- to 23-kDa virion component that forms a stable complex with the 14-kDa envelope protein (A27L gene). In a previous report, we described the construction of a VV recombinant, VVindA17L, in which the expression of the A17L gene is inducibly regulated by isopropyl-beta-D-thiogalactoside (IPTG). We demonstrated that shutoff of the A17L gene results in a blockade of virion morphogenesis at a very early stage (D. Rodríguez, M. Esteban, and J. R. Rodríguez, J. Virol. 69:4640-4648, 1995). In the present study, we show that virus growth is restored if the inducer is provided not later than 6 h postinfection. Immunofluorescence and immunoelectron microscopy analysis of VVindA17L-infected cells revealed that in the absence of the 21- to 23-kDa protein, the 14-kDa protein is distributed throughout the cytoplasm. After IPTG addition, the 14-kDa protein can be detected around viral factories and immature virions; at later times, it localizes in the external membranes of intracellular mature virions. Immunoelectron microscopy with anti-21- to 23-kDa antibodies showed that soon after induction, the protein accumulates in membranes of the rough endoplasmic reticulum and in the nuclear envelope. With time, the protein localizes in viral crescents and subsequently associates to the membranes of immature and intracellular mature virions. These results are consistent with a model in which the 21- to 23-kDa protein would be synthesized at the endoplasmic reticulum, from where the protein could be translocated to the membranes of the intermediate compartment to generate the precursors of the viral membranes. Also, these results argue that 14-kDa envelope protein becomes posttranslationally associated to viral membranes through its interaction with the 21-kDa protein.",,"['Rodríguez, D', 'Risco, C', 'Rodríguez, J R', 'Carrascosa, J L', 'Esteban, M']",,,,
,PMC,Uptake and incorporation of an epitope-tagged sialic acid donor into intact rat liver Golgi compartments. Functional localization of sialyltransferase overlaps with beta-galactosyltransferase but not with sialic acid O-acetyltransferase.,,PMC276019,,,"The transfer of sialic acids (Sia) from CMP-sialic acid (CMP-Sia) to N-linked sugar chains is thought to occur as a final step in their biosynthesis in the trans portion of the Golgi apparatus. In some cell types such Sia residues can have O-acetyl groups added to them. We demonstrate here that rat hepatocytes express 9-O-acetylated Sias mainly at the plasma membranes of both apical (bile canalicular) and basolateral (sinusoidal) domains. Golgi fractions also contain 9-O-acetylated Sias on similar N-linked glycoproteins, indicating that O-acetylation may take place in the Golgi. We show here that CMP-Sia-FITC (with a fluorescein group attached to the Sia) is taken up by isolated intact Golgi compartments. In these preparations, Sia-FITC is transferred to endogenous glycoprotein acceptors and can be immunochemically detected in situ. Addition of unlabeled UDP-Gal enhances Sia-FITC incorporation, indicating a substantial overlap of beta-galactosyltransferase and sialyltransferase machineries. Moreover, the same glycoproteins that incorporate Sia-FITC also accept [3H]galactose from the donor UDP-[3H]Gal. In contrast, we demonstrate with three different approaches (double-labeling, immunoelectron microscopy, and addition of a diffusible exogenous acceptor) that sialyltransferase and O-acetyltransferase machineries are much more separated from one another. Thus, 9-O-acetylation occurs after the last point of Sia addition in the trans-Golgi network. Indeed, we show that 9-O-acetylated sialoglycoproteins are preferentially segregated into a subset of vesicular carriers that concentrate membrane-bound, but not secretory, proteins.",,"['Chammas, R', 'McCaffery, J M', 'Klein, A', 'Ito, Y', 'Saucan, L', 'Palade, G', 'Farquhar, M G', 'Varki, A']",,,,
,PMC,"Isotype-specific antibody responses to foot-and-mouth disease virus in sera and secretions of ""carrier' and ""non-carrier' cattle.",,PMC2271708,,,"Isotype-specific antibody responses to foot-and-mouth disease virus (FMDV) were measured in the sera and upper respiratory tract secretions of vaccinated and susceptible cattle challenged with FMDV by direct contact or by intranasal inoculation. A comparison was made between cattle that eliminated FMDV and those that developed and maintained a persistent infection. Serological and mucosal antibody responses were detected in all animals after challenge. IgA and IgM were detected before the development of IgG1 and IgG2 responses. IgM was not detected in vaccinated cattle. Challenge with FMDV elicited a prolonged biphasic secretory antibody response in FMDV ""carrier' animals only. The response was detected as FMDV-specific IgA in both mucosal secretions and serum samples, which gained statistical significance (P < 0.05) by 5 weeks after challenge. This observation could represent the basis of a test to differentiate vaccinated and/or recovered convalescent cattle from FMDV ""carriers'.",,"['Salt, J. S.', 'Mulcahy, G.', 'Kitching, R. P.']",,,,
,PMC,Comparison of reverse transcription-PCR with tissue culture and other rapid diagnostic assays for detection of type A influenza virus.,,PMC229331,,,"We applied a reverse transcription (RT)-PCR assay for influenza A virus to combined nasal wash-throat swab specimens previously obtained from an outpatient pediatric population with acute respiratory illness during concurrent epidemics of influenza A virus and respiratory syncytial virus. The results of the RT-PCR assay were compared with those previously reported with virus cultivation and commercially available rapid diagnostic kits (E.A. Dominguez, L.H. Taber, and R.B. Couch, J. Clin. Microbiol. 31:2286-2290, 1993). With virus cultivation as the ""gold standard"", the RT-PCR assay had a sensitivity, specificity, and efficiency of 95, 98, and 97%, respectively, compared with 75, 100, and 93%, respectively, for the best diagnostic kit (Becton Dickinson Directigen). RT-PCR is an effective alternative to virus isolation for the detection of influenza A virus in clinical specimens.",,"['Atmar, R L', 'Baxter, B D', 'Dominguez, E A', 'Taber, L H']",,,,
,PMC,Analysis of the serotype-specific epitopes of avian infectious bronchitis virus strains Ark99 and Mass41.,,PMC190784,,,"The Ark and Mass serotype-specific epitopes of infectious bronchitis virus were studied by immunofluorescence and immunoprecipitation of mutant and recombinant spike glycoproteins (S protein) expressed in mouse L cells. Serotype-specific monoclonal antibodies could bind to the recombinant proteins of Ark99 and Mass41 expressed from the chimeras in which the N-terminal thirds of the S1 sequences were reciprocally exchanged. Therefore, it appears that the respective serotype-specific epitopes of both strains were localized within the C-terminal two-thirds of the S1 proteins. Deletion and insertion of a five-amino-acid fragment on the S1 proteins of Ark99 and Mass41, altered the serotype-specific epitopes. This result implies that the five-amino-acid insertion on the S1 protein of the Ark serotype was involved in determining the conformation of the protein, probably acting as a spacer. In addition, it appears that an interaction between sequences of the N-terminal third and the remaining portion of the S1 protein determines the tertiary structure of the protein as well as the conformation of the serotype-specific epitope.",,"['Jia, W', 'Wang, X', 'Parrish, C R', 'Naqi, S A']",,,,
,PMC,The 3' untranslated region of coronavirus RNA is required for subgenomic mRNA transcription from a defective interfering RNA.,,PMC190780,,,"The 3'-end of mouse hepatitis virus (MHV) genomic RNA contains a recognition sequence (55 nucleotides [nt]) required for minus-strand RNA synthesis. To determine whether the 3'-end sequence is also involved in subgenomic mRNA transcription, we have constructed MHV defective interfering (DI) RNAs which contain a chloramphenicol acetyltransferase (CAT) gene placed behind an intergenic sequence and a 3'-end sequence with various degrees of internal deletions. The DI RNAs were transfected into MHV-infected cells, and CAT activities, which represent subgenomic mRNA transcription from the intergenic site, were determined. The results demonstrated that the deletions of sequence upstream of the 350 nt at the 3'-end, which include the 3'-untranslated region (3'-UTR), of MHV genomic RNA did not affect subgenomic mRNA transcription. However, deletions that reduced the 3'-end sequences to 270 nt or less completely abolished the mRNA transcription despite the fact that all of these clones synthesized minus-strand RNAs. These results indicated that mRNA transcription from an intergenic site in the MHV DI RNA requires most of the 3'-UTR as a cis-acting signal, which likely exerts its effects during plus-strand RNA synthesis. A substitution of the corresponding bovine coronavirus sequence for the MHV sequence within nt 270 to 305 from the 3'-end abrogated the CAT gene expression, suggesting a very rigid sequence requirement in this region. The deletion of a putative pseudoknot structure within the 3'-UTR also abolished the CAT gene expression. These findings suggest that the 3'-UTR may interact with the other RNA regulatory elements to regulate mRNA transcription.",,"['Lin, Y J', 'Zhang, X', 'Wu, R C', 'Lai, M M']",,,,
,PMC,Murine infection with lymphocytic choriomeningitis virus following gastric inoculation.,,PMC190775,,,"Laboratory studies of arenaviruses have been limited to parenteral routes of infection; however, recent epidemiological studies implicate virus ingestion as a natural route of infection. Accordingly, we developed a model for oral and gastric infection with lymphocytic choriomeningitis virus to enable studies of mucosal transmission and vaccination by this additional route.",,"['Rai, S K', 'Cheung, D S', 'Wu, M S', 'Warner, T F', 'Salvato, M S']",,,,
,PMC,"A vaccinia virus core protein, p39, is membrane associated.",,PMC190740,,,"We describe herein the characterization of p39, the product of the A4L gene of vaccinia virus. By immunolabelling of thawed cryosections from infected HeLa cells, we show that this protein is initially located in the central region, or viroplasm, of the viral factories, as well as in the immature virions, with very small amounts of labelling observed on the surrounding membranes. The localization of p39 changes dramatically during the transition of the immature virion to the intracellular mature virus (IMV), coincident with the appearance of the core structure in the center of the IMV, with p39 located between this core and the surrounding membranes. Complementary biochemical data, such as partitioning into the Triton X-114 detergent phase and stripping of the viral membranes with Nonidet P-40 and dithiothreitol, suggest that p39 is associated with the innermost of the two membranes surrounding the core. Sodium carbonate treatment also indicates that p39 is associated with membranes, even at the early stages of viral assembly. However, following in vitro translation of p39 in the presence of microsomal membranes, we failed to detect any association of the independently expressed protein with membranes. We also failed to detect any posttranslational acylation of p39 with myristate or palmitate, suggesting that p39 does not achieve its membrane association through lipid anchors. Therefore, p39 is most likely membrane associated through an interaction with an integral membrane protein(s) present in the innermost of the two membranes surrounding the IMV. These data, together with our recent data showing that p39 colocalizes with the spike-like protrusions on the IMV core (N. Roos, M. Cyrklaff, S. Cudmore, R. Blasco, J. Krijnse-Locker, and G. Griffiths, EMBO J. 15:2343-2355, 1996), suggest that p39 may form part of this spike and that it possibly functions as a matrix-like linker protein between the core and the innermost of the two membranes surrounding the IMV.",,"['Cudmore, S', 'Blasco, R', 'Vincentelli, R', 'Esteban, M', 'Sodeik, B', 'Griffiths, G', 'Krijnse Locker, J']",,,,
,PMC,Processing of the equine arteritis virus replicase ORF1b protein: identification of cleavage products containing the putative viral polymerase and helicase domains.,,PMC190703,,,"The replicase open reading frame lb (ORF1b) protein of equine arteritis virus (EAV) is expressed from the viral genome as an ORF1ab fusion protein (345 kDa) by ribosomal frameshifting. Processing of the ORF1b polyprotein was predicted to be mediated by the nsp4 serine protease, the main EAV protease. Several putative cleavage sites for this protease were detected in the ORF1b polyprotein. On the basis of this tentative processing scheme, peptides were selected to raise rabbit antisera that were used to study the processing of the EAV replicase ORF1b polyprotein (158 kDa). In immunoprecipitation and immunoblotting experiments, processing products of 80, 50, 26, and 12 kDa were detected. Of these, the 80-kDa and the 50-kDa proteins contain the putative viral polymerase and helicase domains, respectively. Together, the four cleavage products probably cover the entire ORF1b-encoded region of the EAV replicase, thereby representing the first complete processing scheme of a coronaviruslike ORF1b polyprotein. Pulse-chase analysis revealed that processing of the ORF1b polyprotein is slow and that several large precursor proteins containing both ORF1a- and ORF1b-encoded regions are generated. The localization of ORF1b-specific proteins in the infected cell was studied by immunofluorescence. A perinuclear staining was observed, which suggests association with a membranous compartment.",,"['van Dinten, L C', 'Wassenaar, A L', 'Gorbalenya, A E', 'Spaan, W J', 'Snijder, E J']",,,,
,PMC,Persistent reovirus infections of L cells select mutations in viral attachment protein sigma1 that alter oligomer stability.,,PMC190700,,,"During maintenance of L-cell cultures persistently infected with reovirus, mutations are selected in viruses and cells. Cells cured of persistent infection support growth of viruses isolated from persistently infected cultures (PI viruses) significantly better than that of wild-type (wt) viruses. In a previous study, the capacity of PI virus strain L/C to grow better than wt strain type 1 Lang (T1L) in cured cells was mapped genetically to the S1 gene (R. S. Kauffman, R. Ahmed, and B. N. Fields, Virology 131:79-87, 1983), which encodes viral attachment protein sigma1. To investigate mechanisms by which mutations in S1 confer growth of PI viruses in cured cells, we determined the S1 gene nucleotide sequences of L/C virus and six additional PI viruses isolated from independent persistently infected L-cell cultures. The S1 sequences of these viruses contained from one to three mutations, and with the exception of PI 2A1 mutations in each S1 gene resulted in changes in the deduced amino acid sequence of sigma1 protein. Using electrophoresis conditions that favor migration of sigma1 oligomers, we found that sigma1 proteins of L/C, PI 1A1, PI 3-1, and PI 5-1 migrated as monomers, whereas sigma1 proteins of wt reovirus and PI 2A1 migrated as oligomers. These findings suggest that mutations in sigma1 protein affecting stability of sigma1 oligomers are important for the capacity of PI viruses to infect mutant cells selected during persistent infection. Since no mutation was found in the deduced amino acid sequence of PI 2A1 sigma1 protein, we used T1L X PI 2A1 reassortant viruses to identify viral genes associated with the capacity of this PI virus to grow better than wt in cured cells. The capacity of PI 2A1 to grow better than T1L in cured cells was mapped to the S4 gene, which encodes outer-capsid protein sigma3. This finding suggests that in some cases, mutations in sigma3 protein in the absence of sigma1 mutations confer growth of PI viruses in mutant cells. To confirm the importance of the S1 gene in PI virus growth in cured cells, we used T1L X PI 3-1 reassortant viruses to genetically map the capacity of this PI virus to grow better than wt in cured cells. In contrast to our results using PI 2A1, we found that growth of PI 3-1 in cured cells was determined by the sigma1-encoding S1 gene. Given that the sigma1 and sigma3 proteins play important roles in reovirus disassembly, findings made in this study suggest that stability of the viral outer capsid is an important determinant of the capacity of reoviruses to adapt to host cells during persistent infection.",,"['Wilson, G J', 'Wetzel, J D', 'Puryear, W', 'Bassel-Duby, R', 'Dermody, T S']",,,,
,PMC,Attachment and entry of recombinant Norwalk virus capsids to cultured human and animal cell lines.,,PMC190699,,,"Norwalk virus (NV) is the prototype strain of a group of noncultivable human caliciviruses responsible for epidemic outbreaks of acute gastroenteritis. While these viruses do not grow in tissue culture cells or animal models, expression of the capsid protein in insect cells results in the self-assembly of recombinant Norwalk virus-like particles (rNV VLPs) that are morphologically and antigenically similar to native NV. We have used these rNV VLPs to examine virus-cell interactions. Binding and internalization of VLPs to cultured human and animal cell lines were studied in an attempt to identify potentially susceptible cell lines for virus propagation in vitro and to determine if early events in the replication cycle were responsible for the narrow host range and restriction of virus growth in cell culture. Radiolabeled VLPs specifically bound to a saturable number of binding molecules on the cell surface of 13 cell lines from different origins, including human intestine (differentiated and undifferentiated Caco-2) and insect (Spodoptera frugiperda 9) ovary. Differentiated Caco-2 cells bound significantly more rNV VLPs than the other cell lines. Variations in the amount of bound VLPs among the different cell lines did not correlate with the tissue or species of origin. VLP binding was specific, as determined by competition experiments with unlabeled rNV VLPs; however, only 1.4 to 6.8% of the specifically prebound radiolabeled VLPs became internalized into cells. Blocking experiments using polygonal and monoclonal anti-rNV sera and specific antipeptide sera were performed to map the domains on rNV VLPs involved in binding to cells. One monoclonal antibody (NV8812) blocked binding of rNV VLPs to human and animal cell lines. The binding site of monoclonal antibody NV8812 was localized to the C-terminal 300 to 384 residues of the capsid protein by immunoprecipitation with truncated and cleaved forms of the capsid protein. These data suggest that the C-terminal region of the capsid protein is involved in specific binding of rNV VLPs to cells.",,"['White, L J', 'Ball, J M', 'Hardy, M E', 'Tanaka, T N', 'Kitamoto, N', 'Estes, M K']",,,,
,PMC,Cellular origin and ultrastructure of membranes induced during poliovirus infection.,,PMC190698,,,"Poliovirus RNA replicative complexes are associated with cytoplasmic membranous structures that accumulate during viral infection. These membranes were immunoisolated by using a monoclonal antibody against the viral nonstructural protein 2C. Biochemical analysis of the isolated membranes revealed that several organelles of the host cell (lysosomes, trans-Golgi stack and trans-Golgi network, and endoplasmic reticulum) contributed to the virus-induced membranous structures. Electron microscopy of infected cells preserved by high-pressure freezing revealed that the virus-induced membranes contain double lipid bilayers that surround apparently cytosolic material. Immunolabeling experiments showed that poliovirus proteins 2C and 3D were localized to the same membranes as the cellular markers tested. The morphological and biochemical data are consistent with the hypothesis that autophagy or a similar host process is involved in the formation of the poliovirus-induced membranes.",,"['Schlegel, A', 'Giddings, T H', 'Ladinsky, M S', 'Kirkegaard, K']",,,,
,PMC,Viability and infectivity of Cryptosporidium parvum oocysts are retained upon intestinal passage through a refractory avian host.,,PMC168119,,,"Six Cryptosporidium-free Peking ducks (Anas platyrhynchos) were each orally inoculated with 2.0 x 10(6) Cryptosporidium parvum oocysts infectious to neonatal BALB/c mice. Histological examination of the stomachs jejunums, ilea, ceca, cloacae, larynges, tracheae, and lungs of the ducks euthanized on day 7 postinoculation (p.i.) revealed no life-cycle stages of C. parvum. However, inoculum-derived oocysts extracted from duck feces established severe infection in eight neonatal BALB/c mice (inoculum dose, 2.5 x 10(5) per mouse). On the basis of acid-fast stained direct wet smears, 73% of the oocysts in duck feces were intact (27% were oocyst shells), and their morphological features conformed to those of viable and infectious oocysts of the original inoculum. The fluorescence scores of the inoculated oocysts, obtained by use of the MERIFLUOR test, were identical to those obtained for the feces-recovered oocysts (the majority were 3+ to 4+). The dynamics of oocyst shedding showed that the birds released a significantly higher number of intact oocysts than the oocyst shells (P < 0.01). The number of intact oocysts shed (87%) during the first 2 days p.i. was significantly higher than the number shed during the remaining 5 days p.i. (P < 0.01) and significantly decreased from day 1 to day 2 p.i. (P < 0.01). The number of oocyst shells shed during 7 days p.i. did not vary significantly (P > 0.05). The retention of infectivity of C. parvum oocysts after intestinal passage through an aquatic bird has serious epidemiological and epizootiological implications. Waterfowl may serve as mechanical vectors for the waterborne oocysts and may enhance contamination of surface waters with C. parvum. As the concentration of Cryptosporidium oocysts in source waters is attributable to watershed management practices, the watershed protection program should consider waterfowl as a potential factor enhancing contamination of the source water with C. parvum.",,"['Graczyk, T K', 'Cranfield, M R', 'Fayer, R', 'Anderson, M S']",,,,
,PMC,"Prevalence of antibodies to feline parvovirus, calicivirus, herpesvirus, coronavirus, and immunodeficiency virus and of feline leukemia virus antigen and the interrelationship of these viral infections in free-ranging lions in east Africa.",,PMC170405,,,"While viral infections and their impact are well studied in domestic cats, only limited information is available on their occurrence in free-ranging lions. The goals of the present study were (i) to investigate the prevalence of antibodies to feline calicivirus (FCV), herpesvirus (FHV), coronavirus (FCoV), parvovirus (FPV), and immunodeficiency virus (FIV) and of feline leukemia virus (FeLV) antigen in 311 serum samples collected between 1984 and 1991 from lions inhabiting Tanzania's national parks and (ii) to evaluate the possible biological importance and the interrelationship of these viral infections. Antibodies to FCV, never reported previously in free-ranging lions, were detected in 70% of the sera. In addition, a much higher prevalence of antibodies to FCoV (57%) was found than was previously reported in Etosha National Park and Kruger National Park. Titers ranged from 25 to 400. FeLV antigen was not detectable in any of the serum samples. FCoV, FCV, FHV, and FIV were endemic in the Serengeti, while a transient elevation of FPV titers pointed to an outbreak of FPV infection between 1985 and 1987. Antibody titers to FPV and FCV were highly prevalent in the Serengeti (FPV, 75%; FCV, 67%) but not in Ngorongoro Crater (FPV, 27%; FCV, 2%). These differences could be explained by the different habitats and biological histories of the two populations and by the well-documented absence of immigration of lions from the Serengeti plains into Ngorongoro Crater after 1965. These observations indicate that, although the pathological potential of these viral infections seemed not to be very high in free-ranging lions, relocation of seropositive animals by humans to seronegative lion populations must be considered very carefully.",,"['Hofmann-Lehmann, R', 'Fehr, D', 'Grob, M', 'Elgizoli, M', 'Packer, C', 'Martenson, J S', ""O'Brien, S J"", 'Lutz, H']",,,,
,PMC,Antibody responses against the G and F proteins of bovine respiratory syncytial virus after experimental and natural infections.,,PMC170396,,,"Antibodies against the two major surface glycoproteins of bovine respiratory syncytial virus (BRSV), G and F, play a role in protection against BRSV-associated disease, but only the antibody response against the F protein has been well described. Therefore, we used a novel peptide-based enzyme-linked immunosorbent assay (G peptide-ELISA) to compare immunoglobulin G (IgG) and IgG subclass antibody responses against the G protein with the antibody response against the F protein, as measured by a conventional BRSV ELISA (F-ELISA). Experimental infection of cattle induced significantly lower antibody titers than did natural infection. After natural primary infection, G peptide-specific antibodies declined more rapidly and to lower levels than the F protein-specific antibodies. As a consequence, the G peptide-ELISA detected more reinfections than did the F-ELISA. Ratios of G- and F-specific IgG1/IgG2 antibody titers did not differ markedly after infection or vaccination. Interestingly, after natural infection calves did not develop an IgG2 response to the complete G protein. In contrast, adult cattle had high IgG2 titers against this protein. Vaccination with a live vaccine induced low antibody titers, similar to the titers after experimental infection, whereas vaccination with an inactivated vaccine induced high titers. The results indicate that the kinetics of the G- and F-specific antibody responses differ. Furthermore, the IgG subclass response against the unglycosylated central region of the G protein is similar to the IgG subclass response to the F protein, but the IgG subclass response differs from the response to the complete G protein.",,"['Schrijver, R S', 'Langedijk, J P', 'van der Poel, W H', 'Middel, W G', 'Kramps, J A', 'van Oirschot, J T']",,,,
,PMC,Serological and molecular evidence of enterovirus infection in patients with end-stage dilated cardiomyopathy.,,PMC484515,,,"OBJECTIVE: To study the relative diagnostic value of enterovirus-specific molecular biological and serological assays in patients with end-stage dilated cardiomyopathy, and to investigate the possible role of other cardiotropic viruses in dilated cardiomyopathy. DESIGN: Analysis of recipient myocardial tissue and serum from patients with dilated cardiomyopathy and controls undergoing cardiac transplantation for end-stage cardiac disease. SETTING: University virology department and transplantation unit. METHODS: Reverse transcriptase-polymerase chain reaction and nucleotide sequence analysis of myocardial RNA and DNA; enterovirus-specific in situ hybridization; enterovirus-specific immunoglobulin M detection. RESULTS: Enterovirus RNA was detected in myocardial tissue from only a small proportion of (five of 75) hearts. However, although enterovirus-specific immunoglobulin M responses were detected in 22 (28%) of 39 controls patients, a significantly higher prevalence was observed among patients with dilated cardiomyopathy (22 (56%) of 39 patients; P < 0.005). All enteroviruses detected in myocardium showed greatest nucleotide sequence homology with coxsackievirus type B3. Detection of enterovirus RNA in myocardium by the polymerase chain reaction and by in situ hybridisation gave comparable results. Other potentially cardiotropic virus genomes, including human cytomegalovirus, influenzaviruses, and coronaviruses were not detected in myocardium. CONCLUSION: This study found that enterovirus-specific immunoglobulin M responses provided the strongest evidence of enterovirus involvement in patients with end-stage dilated cardiomyopathy. However, the high background prevalence of these responses limits their diagnostic value. The finding that enteroviruses detected in myocardium were coxsackievirus type B3 accords with recent findings in patients with acute myocarditis, and indicates that this serotype is the major cardiotropic human enterovirus.",,"['Muir, P.', 'Nicholson, F.', 'Illavia, S. J.', 'McNeil, T. S.', 'Ajetunmobi, J. F.', 'Dunn, H.', 'Starkey, W. G.', 'Reetoo, K. N.', 'Cary, N. R.', 'Parameshwar, J.', 'Banatvala, J. E.']",,,,
,PMC,Replication of murine coronavirus defective interfering RNA from negative-strand transcripts.,,PMC190590,,,"The positive-strand defective interfering (DI) RNA of the murine coronavirus mouse hepatitis virus (MHV), when introduced into MHV-infected cells, results in DI RNA replication and accumulation. We studied whether the introduction of negative-strand transcripts of MHV DI RNA would also result in replication. At a location downstream of the T7 promoter and upstream of the human hepatitis delta virus ribozyme domain, we inserted a complete cDNA clone of MHV DI RNA in reverse orientation; in vitro-synthesized RNA from this plasmid yielded a negative-strand RNA copy of the MHV DI RNA. When the negative-strand transcripts of the DI RNA were expressed in MHV-infected cells by a vaccinia virus T7 expression system, positive-strand DI RNAs accumulated in the plasmid-transfected cells. DI RNA replication depended on the expression of T7 polymerase and on the presence of the T7 promoter. Transfection of in vitro-synthesized negative-strand transcripts into MHV-infected cells and serial passage of virus samples from RNA-transfected cells also resulted in accumulation of the DI RNA. Positive-strand DI RNA transcripts were undetectable in sample preparations of the in vitro-synthesized negative-strand DI RNA transcripts, and DI RNA did not accumulate after cotransfection of a small amount of positive-strand DI RNA and truncated-replication-disabled negative-strand transcripts; clearly, the DI RNA replicated from the transfected negative-strand transcripts and not from minute amounts of positive-strand DI RNAs that might be envisioned as artifacts of T7 transcription. Sequence analysis of positive-strand DI RNAs in the cells transfected with negative-strand transcripts showed that DI RNAs maintained the DI-specific unique sequences introduced within the leader sequence. These data indicated that positive-strand DI RNA synthesis occurred from introduced negative-strand transcripts in the MHV-infected cells; this demonstration, using MHV, of DI RNA replication from transfected negative-strand DI RNA transcripts is the first such demonstration among all positive-stranded RNA viruses.",,"['Joo, M', 'Banerjee, S', 'Makino, S']",,,,
,PMC,RNA-protein interactions in regulation of picornavirus RNA translation.,,PMC239454,,,"The translation of picornavirus RNA occurs by a cap-independent mechanism directed by a region of about 450 nucleotides from the 5' untranslated region, termed an internal ribosome entry site (IRES). Internal initiation of protein synthesis occurs without any requirement for viral proteins. Furthermore, it is maintained when host cell protein synthesis is almost abolished. By using in vitro translation systems, two distinct families of IRES elements which have very different predicted RNA secondary structures have been defined. The cardiovirus and aphthovirus elements function very efficiently in rabbit reticulocyte lysate, whereas the enterovirus and rhinovirus elements function poorly in this system. However, supplementation of this translation system with additional cellular proteins can stimulate translation directed by the enterovirus and rhinovirus RNAs and reduce production of aberrant initiation products. The characterization of cellular proteins interacting with the picornavirus IRES is a major focus of research. Many different protein species can be observed to interact with regions of the IRES by in vitro analyses, e.g., UV cross-linking. However, the function and significance of many of these interactions are not always known. For two proteins, La and the polypyrimidine tract-binding protein, evidence has been obtained for a functional role of their interaction with IRES elements.",,"['Belsham, G J', 'Sonenberg, N']",,,,
,PMC,Surprising deficiency of CENP-B binding sites in African green monkey alpha-satellite DNA: implications for CENP-B function at centromeres.,,PMC231516,,,"Centromeres of mammalian chromosomes are rich in repetitive DNAs that are packaged into specialized nucleoprotein structures called heterochromatin. In humans, the major centromeric repetitive DNA, alpha-satellite DNA, has been extensively sequenced and shown to contain binding sites for CENP-B, an 80-kDa centromeric autoantigen. The present report reveals that African green monkey (AGM) cells, which contain extensive alpha-satellite arrays at centromeres, appear to lack the well-characterized CENP-B binding site (the CENP-B box). We show that AGM cells express a functional CENP-B homolog that binds to the CENP-B box and is recognized by several independent anti-CENP-B antibodies. However, three independent assays fail to reveal CENP-B binding sites in AGM DNA. Methods used include a gel mobility shift competition assay using purified AGM alpha-satellite, a novel kinetic electrophoretic mobility shift assay competition protocol using bulk genomic DNA, and bulk sequencing of 76 AGM alpha-satellite monomers. Immunofluorescence studies reveal the presence of significant levels of CENP-B antigen dispersed diffusely throughout the nuclei of interphase cells. These experiments reveal a paradox. CENP-B is highly conserved among mammals, yet its DNA binding site is conserved in human and mouse genomes but not in the AGM genome. One interpretation of these findings is that the role of CENP-B may be in the maintenance and/or organization of centromeric satellite DNA arrays rather than a more direct involvement in centromere structure.",,"['Goldberg, I G', 'Sawhney, H', 'Pluta, A F', 'Warburton, P E', 'Earnshaw, W C']",,,,
,PMC,Role of enteric pathogens in the aetiology of neonatal diarrhoea in lambs and goat kids in Spain.,,PMC2271684,,,"Faeces samples from diarrhoeic and non-diarrhoeic lambs and goat kids aged 1-45 days were examined for enteric pathogens. Cryptosporidium parvum was detected in both diarrhoeic lambs (45%) and goat kids (42%) but not in non-diarrhoeic animals. F5+ (K99+) and/or F41+ Escherichia coli strains were isolated from 26% and 22% of the diarrhoeic lambs and goat kids, respectively, although these strains, which did not produce enterotoxins ST I or LT I, were found with similar frequencies in non-diarrhoeic animals. A F5-F41-ST I+ E. coli strain was isolated from a diarrhoeic lamb (0.6%). Verotoxigenic E. coli was isolated from both diarrhoeic and non-diarrhoeic lambs (4.1% and 8.2%, respectively) and there was no association between infection and diarrhoea. The prevalence of group A rotavirus infection in diarrhoeic lambs was very low (2.1%). Groups A and B rotaviruses were detected in three (8.1%) and five (13.5%) diarrhoeic goat kids from two single outbreaks. Group C rotaviruses were detected in four non-diarrhoeic goat kids. An association of diarrhoea and infection was demonstrated only for group B rotavirus. Clostridium perfringens was isolated from 10.8% of the diarrhoeic goat kids but not from non-diarrhoeic goat kids or lambs. Salmonella arizonae was isolated from a diarrhoeic goat kid (2.7%) and the clinical characteristics of the outbreaks where these two latter enteropathogens were found different from the rest. Picobirnaviruses were detected in a diarrhoeic lamb. No coronaviruses were detected using a bovine coronavirus ELISA. No evidence was found of synergistic effect between the agents studied. Enteric pathogens were not found in four (8.7%) and three (20%) outbreaks of diarrhoea in lambs and goat kids, respectively.",,"['Muñoz, M.', 'Alvarez, M.', 'Lanza, I.', 'Cármenes, P.']",,,,
,PMC,A conserved motif in S-layer proteins is involved in peptidoglycan binding in Thermus thermophilus.,,PMC178255,,,"There is experimental evidence to suggest that the 100-kDa S-layer protein from Thermus thermophilus HB8 binds to the peptidoglycan cell wall. This property could be related to the presence of a region (SLH) of homology with other S-layer proteins and extracellular enzymes (A. Lupas, H. Engelhardt, J. Peters, U. Santarius, S. Volker, and W. Baumeister, J. Bacteriol. 176:1224-1233, 1994). By using specific monoclonal antibodies, we show that similar regions are present in different members of the Deinococcus-Thermus phylogenetic group. To analyze the role that the SLH domain plays in vivo and in vitro in T. thermophilus, we have obtained a mutant form (slpA.X) of the S-layer gene (slpA) in which the SLH domain was deleted. The slpA.X gene was inserted into the chromosome of the thermophile by gene replacement, resulting in a mutant which expressed a major membrane protein with the size expected from the construction (90 kDa). This protein was identified as the product of slpA.X by its differential reaction with monoclonal antibodies. Mutants expressing the SlpA.X protein grow as groups of cells, surrounded by a common external envelope of trigonal symmetry that contains the SlpA.X protein as a main component, thus showing the inability of the SLH-defective protein to attach to the underlying material in vivo. In addition, averaged images of SlpA.X-rich fractions showed a regular arrangement, identical to that built up by the wild-type (SlpA) protein in the absence of peptidoglycan. Finally, we demonstrate by Western blotting (immunoblotting) the direct role of the SLH domain in the binding of the S-layer of T. thermophilus HB8 to the peptidoglycan layer.",,"['Olabarría, G', 'Carrascosa, J L', 'de Pedro, M A', 'Berenguer, J']",,,,
,PMC,Rabbit sucrase-isomaltase contains a functional intestinal receptor for Clostridium difficile toxin A.,,PMC507473,,,"The intestinal effects of Clostridium difficile toxin A are inidated by toxin binding to luminal enterocyte receptors. We reported previously that the rabbit ileal brush border (BB) receptor is a glycoprotein with an alpha-d-galactose containing trisaccharide in the toxin-binding domain (1991. J. Clin. Invest. 88:119-125). In this study we characterized the rabbit ileal BB receptor for this toxin. Purified toxin receptor peptides of 19 and 24 amino acids showed 100% homology with rabbit sucrase-isomaltase (SI). Guinea pig receptor antiserum reacted in Western blots with rabbit SI and with the purified toxin receptor. Antireceptor IgG blocked in vitro binding of toxin A to rabbit ileal villus cell BB. Furthermore, anti-SI IgG inhibited toxin A-induced secretion (by 78.1%, P < 0.01), intestinal permeability (by 80.8%, P < 0.01), and histologic injury (P < 0.01) in rabbit ileal loops in vivo. Chinese hamster ovary cells transfected with SI cDNA showed increased intracellular calcium increase in response to native toxin (holotoxin) or to a recombinant 873-amino acid peptide representing the receptor binding domain of toxin A. These data suggest that toxin A binds specifically to carbohydrate domains on rabbit ileal SI, and that such binding is relevant to signal transduction mechanisms that mediate in vitro and in vivo toxicity.",,"['Pothoulakis, C', 'Gilbert, R J', 'Cladaras, C', 'Castagliuolo, I', 'Semenza, G', 'Hitti, Y', 'Montcrief, J S', 'Linevsky, J', 'Kelly, C P', 'Nikulasson, S', 'Desai, H P', 'Wilkins, T D', 'LaMont, J T']",,,,
,PMC,Neutralizing antibodies to different proteins of African swine fever virus inhibit both virus attachment and internalization.,,PMC190536,,,"African swine fever virus induces in convalescent pigs antibodies that neutralized the virus before and after binding to susceptible cells, inhibiting both virus attachment and internalization. A further analysis of the neutralization mechanisms mediated by the different viral proteins showed that antibodies to proteins p72 and p54 are involved in the inhibition of a first step of the replication cycle related to virus attachment, while antibodies to protein p30 are implicated in the inhibition of virus internalization.",,"['Gómez-Puertas, P', 'Rodríguez, F', 'Oviedo, J M', 'Ramiro-Ibáñez, F', 'Ruiz-Gonzalvo, F', 'Alonso, C', 'Escribano, J M']",,,,
,PMC,"Transmissible gastroenteritis coronavirus, but not the related porcine respiratory coronavirus, has a sialic acid (N-glycolylneuraminic acid) binding activity.",,PMC190524,,,"The hemagglutinating activity of transmissible gastroenteritis virus (TGEV), an enteric porcine coronavirus, was analyzed and found to be dependent on the presence of alpha-2,3-linked sialic acid on the erythrocyte surface. N-Glycolylneuraminic acid was recognized more efficiently by TGEV than was N-acetylneuraminic acid. For an efficient hemagglutination reaction the virions had to be treated with sialidase. This result suggests that the sialic acid binding site is blocked by virus-associated competitive inhibitors. Porcine respiratory coronavirus (PRCV), which is serologically related to TGEV but not enteropathogenic, was found to be unable to agglutinate erythrocytes. Incubation with sialidase did not induce a hemagglutinating activity of PRCV, indicating that the lack of this activity is an intrinsic property of the virus and not due to the presence of competitive inhibitors. Only monoclonal antibodies to an antigenic site that is absent from the S protein of PRCV were able to prevent TGEV from agglutinating erythrocytes. The epitope recognized by these antibodies is located within a stretch of 224 amino acids that is missing in the S protein of PRCV. Our results indicate that the sialic acid binding activity is also located in that portion of the S protein. The presence of a hemagglutinating activity in TGEV and its absence in PRCV open the possibility that the sialic acid binding activity contributes to the enterotropism of TGEV.",,"['Schultze, B', 'Krempl, C', 'Ballesteros, M L', 'Shaw, L', 'Schauer, R', 'Enjuanes, L', 'Herrler, G']",,,,
,PMC,The 5' nontranslated region of potato virus X RNA affects both genomic and subgenomic RNA synthesis.,,PMC190512,,,"A tobacco protoplast system was developed to analyze cis-acting sequences required for potato virus X (PVX) replication. Protoplasts inoculated with transcripts derived from a PVX cDNA clone or from clones containing mutations in their 5' nontranslated regions (NTRs) were assayed for RNA production by S1 nuclease protection assays. A time course of plus- and minus-strand-RNA accumulation indicated that both minus- and plus-strand PVX RNAs were detectable at 0.5 h postinoculation. Although minus-strand RNAs accumulated more rapidly than plus-strand RNAs, maximum levels of plus-strand RNAs were 40- to 80-fold higher. On the basis of these data, time points were chosen for determination of RNA levels in protoplasts inoculated with PVX clones containing deletions or an insertion in their 5' NTRs. Deletions of more than 12 nucleotides from the 5' end, internal deletions, and one insertion in the 5' NTR resulted in substantially decreased levels of plus-strand-RNA production. In contrast, all modified transcripts were functional for minus-strand-RNA synthesis, suggesting that elements in the 5' NTR were not essential for minus-strand-RNA synthesis. Further analysis of the 5' NTR deletion mutants indicated that all mutations that decreased genomic plus-strand-RNA synthesis also decreased synthesis of the two major subgenomic RNAs. These data indicate that cis-acting elements from different regions of the 5' NTR are required for plus-strand-RNA synthesis and that this process may be linked to synthesis of subgenomic RNAs.",,"['Kim, K H', 'Hemenway, C']",,,,
,PMC,Biosynthesis of glycoproteins E and I of feline herpesvirus: gE-gI interaction is required for intracellular transport.,,PMC190504,,,"The biosynthesis of glycoproteins E and I of feline herpesvirus was studied by using the vaccinia virus vTF7-3 expression system. gE and gI were synthesized as N-glycosylated, endoglycosidase H (EndoH)-sensitive precursors with Mrs of 83,000 and 67,000, respectively. When coexpressed, gE and gI formed sodium dodecyl sulfate-sensitive hetero-oligomeric complexes that were readily transported from the endoplasmic reticulum (ER). Concomitantly, the glycoproteins acquired extensive posttranslational modifications, including O glycosylation, leading to an increase in their apparent molecular weights to 95,000 and 80,000 to 100,000 for gE and gI, respectively. In the absence of gE, most gI remained EndoH sensitive. Only a minor population became EndoH resistant, but these molecules were processed aberrantly as indicated by their Mrs (100,000 to 120,000). By immunofluorescence microscopy, gI was detected primarily in the ER but also at the plasma membrane. gE, when expressed by itself, remained EndoH sensitive and was found only in the ER and the nuclear envelope. These results were corroborated by studying the biosynthesis of gE in feline herpesvirus (FHV)-infected cells. In cells infected with wild-type FHV, gE acquired the same co- and posttranslational modifications as during vTF7-3-driven expression. However, an FHV mutant lacking gI failed to produce mature gE. We conclude that gE is retained in the ER, presumably by associating with molecular chaperones, and becomes transport competent only when in a complex with gI.",,"['Mijnes, J D', 'van der Horst, L M', 'van Anken, E', 'Horzinek, M C', 'Rottier, P J', 'de Groot, R J']",,,,
,PMC,"Anterograde, transneuronal transport of herpes simplex virus type 1 strain H129 in the murine visual system.",,PMC190498,,,"Herpes simplex virus (HSV) undergoes retrograde and anterograde axonal transport as it establishes latency and later intermittently reactivates. Most strains of HSV show preferential retrograde transport within the central nervous system (CNS), however. Previous experiments suggest that an exception to this is HSV type 1 (HSV-1) strain H129, since this virus appears to spread primarily in the CNS via anterograde, transneuronal movement. The objective of the present study was to test how specifically this virus spreads in the visual system, a system with well-described neuronal connections. In the present study, the pattern of viral spread was examined following inoculation into the murine vitreous body. Virus was initially detected in the retina and optic tract. Virus then appeared in all known primary targets of the retina, including those in the thalamus (e.g., lateral geniculate complex), hypothalamus (suprachiasmatic nucleus), and superior colliculus (superficial layers). In previous studies, many strains of HSV were shown to infect these structures, even though they spread predominantly in a retrograde direction. However, the H129 strain was unique in then spreading, via anterograde transport, to the primary visual cortex (layer 4 of area 17) via thalamocortical connections. At later times after infection, specific labeling was also detected in other cortical and subcortical areas known to receive projections from the visual cortex. No labeling was ever detected in the contralateral retina, which is consistent with a lack of retrograde spread of HSV-1 strain H129. These results demonstrate the specific anterograde movement of this virus from the retina to subcortical and cortical regions, with no clear evidence for retrograde spread. HSV-1 strain H129 should be generally useful for tracing sensory pathways and may provide the basis for designing a virus vector capable of delivering genetic material via anterograde pathways within the CNS.",,"['Sun, N', 'Cassell, M D', 'Perlman, S']",,,,
,PMC,An eight-nucleotide sequence in the potato virus X 3' untranslated region is required for both host protein binding and viral multiplication.,,PMC190483,,,"Gel retardation and UV-cross-linking techniques were used to demonstrate that two tobacco proteins, with approximate molecular masses of 28 and 32 kDa, bind to a site within the 3' region of potato virus X (PVX) genomic RNA. The protein binding is specific, in that a 50-fold excess of unlabeled probe prevents formation of the complexes but no reduction is observed with a 2,000-fold molar excess of yeast tRNA. Complex formation is inhibited by poly(U) but is relatively unaffected by poly(A), poly(G), or poly(C-I). PVX RNA-host protein complex formation occurs in vitro at salt concentrations up to 400 mM. Deletion mapping indicates that the proteins bind within the 3' untranslated region (UTR) of PVX genomic RNA and that an 8-nucleotide U-rich sequence (5'-UAUUUUCU) is required for the binding. Deletion of the 8-nucleotide U-rich region from the 3' UTR of a sensitive PVX reporter virus that carries the luciferase gene in place of the PVX coat protein gene results in a more than 70,000-fold reduction in luciferase expression in tobacco protoplasts. RNA probes carrying the sequence GCGC in place of the central four contiguous uridines of the 8-nucleotide U-rich motif fail to bind host protein at detectable levels, and the same mutation, when introduced into the PVX reporter virus, eliminates viral multiplication. Mutations of 1 or 2 nucleotides within the same four uridines reduced both binding of host proteins and replication of reporter virus. These results indicate that the 8-nucleotide U-rich motif within the PVX 3' UTR is important for some aspect of viral multiplication and suggest that host protein binding plays a role in the process.",,"['Sriskanda, V S', 'Pruss, G', 'Ge, X', 'Vance, V B']",,,,
,PMC,Nonhomologous RNA-RNA recombination events at the 3' nontranslated region of the Sindbis virus genome: hot spots and utilization of nonviral sequences.,,PMC190470,,,"The mechanism of RNA-RNA recombination at the 3' nontranslated region (3'NTR) of the Sindbis virus (SIN) genome was studied by using nonreplicative RNA precursors. The 11.7-kb SIN genome was transcribed in vitro as two nonoverlapping RNA fragments. RNA-1 contained the entire 11.4-kb protein coding sequence of SIN and also carried an additional 1.8-kb nonviral sequence at its 3' end. RNA-2 carried the remaining 0.26 or 0.3 kb of the SIN genome containing the 3'NTR. Transfection of these two fragments into BHK cells resulted in vivo RNA-RNA recombination and release of infectious SIN recombinants. Eighteen plaque-purified recombinant viruses were sequenced to precisely map the RNA-RNA crossover sites at the 3'NTR. Sixteen of the 18 recombinants were found to be genetically heterogeneous at the 3'NTR. Two major clustered sites within the 3'NTR of RNA-2 were found to be fused to multiple locations on the nonviral sequence of RNA-1, resulting in insertions of 10 to 1,085 nucleotides at the 3'NTR. Sequence analysis of crossover sites suggested only limited homology and heteroduplex-forming capability between substrate RNAs. Analysis of additional 23 recombinant viruses generated by mutagenized donor and acceptor templates supports the occurrence of recombination hot spots on donor templates. Introduction of a 17-nucleotide rudimentary replicase recognition signal in the acceptor template alone did not induce the polymerase to reinitiate at the 17-nucleotide signal. Interestingly, deletion of a 24-nucleotide hot spot locus on the donor template abolished crossover events at one of the two sites and allowed the polymerase to reinitiate at the 17-nucleotide replicase recognition signal inserted at the acceptor template. The possible roles of RNA-protein and RNA-RNA interactions in the differential regulation of apparent pausing, template selection, and reinitiation are discussed.",,"['Hajjou, M', 'Hill, K R', 'Subramaniam, S V', 'Hu, J Y', 'Raju, R']",,,,
,PMC,Accumulation of alfalfa mosaic virus RNAs 1 and 2 requires the encoded proteins in cis.,,PMC190464,,,"RNAs 1 and 2 of the tripartite genome of alfalfa mosaic virus (A1MV) encode the replicase proteins P1 and P2, respectively. P1 expressed in transgenic plants (P1 plants) can be used in trans to support replication of A1MV RNAs 2 and 3, and P2 expressed in transgenic plants (P2 plants) can be used in trans to support replication of A1MV RNAs 1 and 3. Wild-type RNA 1 was able to coreplicate with RNAs 2 and 3 in P1 plants, but this ability was abolished by frameshifts or deletions in the P1 gene of RNA 1. Similarly, wild-type RNA 2 coreplicated with RNAs 1 and 3 in P2 plants, but frameshifts or deletions in the P2 gene of RNA 2 interfered with this replication. Apparently, the P1 and P2 genes are required in cis for the accumulation of RNAs 1 and 2, respectively. Point mutations in the GDD motif of the P2 gene in RNA 2 interfered with accumulation of RNA 2 in P2 plants, indicating that replication of RNA 2 is linked to its translation into a functional protein. Plants transformed with both the P1 and P2 genes (P12 plants) accumulate replicase activity that is able to replicate RNA 3 in trans. An analysis of the time course of the accumulation of RNAs 1, 2, and 3 in protoplasts of P12 plants supported the conclusion that translation and replication are tightly coupled for A1MV RNAs 1 and 2 but not for RNA 3.",,"['van Rossum, C M', 'Garcia, M L', 'Bol, J F']",,,,
,PMC,Comparisons of the F and HN gene sequences of different strains of bovine parainfluenza virus type 3: relationship to phenotype and pathogenicity.,,PMC1263838,,,"The genes for the F and HN glycoprotein of a pathogenic field isolate of bovine parainfluenza virus type 3 (BPIV3) were isolated, converted to cDNA, and sequenced using dideoxynucleotides. The resulting nucleotide sequences were converted to protein sequence and were compared to previously sequenced glycoprotein genes with amino acid differences in the glycoproteins of isolates expressing different phenotypes. The HN glycoprotein, involved in the attachment and release of the virus, and the F glycoprotein, involved in penetration and spread of the virus, have been shown to affect pathogenicity of the virus and are the immunodominant proteins of the virus. Both the F and HN proteins have been shown to be required for syncytium formation. Our results suggest that BPIV3 viruses that exhibit greater syncytium-inducing activity in vitro have greater pathogenicity in vivo. By determining which epitopes are involved in syncytium formation and comparing the sequences and enzymatic activities of different strains of virus, it may be possible to design subunit vaccines that protect against disease.",,"['Breker-Klassen, M M', 'Yoo, D', 'Babiuk, L A']",,,,
,PMC,Comparison of efficacy of sulbactam: ampicillin to ampicillin and saline for treatment of experimentally induced Escherichia coli diarrhea in neonatal calves.,,PMC1263835,,,"A study was conducted to compare the efficacy of sulbactam: ampicillin (SAMP) (3.3:6.6 mg/kg body weight (BW), IM, q24 h) to that of ampicillin trihydrate (AMP) (6 mg/kg BW, IM, q24 h) and 0.9% saline (SAL) (3 mL IM, q24 h) for the treatment of diarrhea in calves induced by oral inoculation with Escherichia coli strain B44 (O9:K30:K99:H-). Treatment was initiated when severe diarrhea was noted (T0) and continued for at least 3 d; or for 24 h after clinical signs resolved; or for a maximum duration of 7 d. Starting at T0, calves were examined twice daily: appetite; rectal temperature (TEMP); and fecal consistency (FECAL), mental status (ATTD), eye position (EYE), and skin elasticity (SKIN) scores were recorded. Feces collected at T0 were submitted for bacteriology, electron microscopy, and parasitology. A complete blood count was performed at T0 and T3 (24 h after third treatment). Severely dehydrated, depressed, and anorexic calves were euthanized and considered mortalities. Cause of death was determined by post mortem examination. A total of 30 calves were included in the study. Three calves were excluded from final analysis. E. coli strain B44 was cultured from feces of all calves at T0. At T2 (24 h after second treatment) mean TEMP of SAMP calves was significantly higher (P < 0.05) than mean TEMP of SAL calves; EYE and SKIN scores of SAMP calves were significantly lower (P < alpha beta = 0.025) than those of SAL and AMP calves; and ATTD and FECAL scores of SAMP calves were significantly lower (P < alpha beta = 0.025) than in SAL calves. At T3, SAMP calves had significantly lower (P < 0.05) mean hematocrit than SAL calves and lower mean total plasma protein concentration than AMP and SAL calves. Mean fibrinogen concentration in SAMP calves at T3 was significantly lower (P < 0.05) than that of calves receiving either SAL or AMP. The number of surviving SAMP calves (10/10) was significantly higher (P < alpha beta = 0.025) than the number of surviving SAL calves (2/9), but not significantly different from the surviving AMP calves (3/8).",,"['Lofstedt, J', 'Miller, L', 'Duizer, G', 'Daley, J']",,,,
,PMC,Definition of cotton rat immunoglobulins: sigmodon species differ in expression of IgG isotypes and production of respiratory syncytial virus antibody.,,PMC1456358,,,"The cotton rat (Sigmodon species) is the preferred animal model for experiments with a number of human pathogens, especially the respiratory viruses. The cotton rat is classified in the family Cricetidae (with hamsters and gerbils) and is a distant cousin of the common laboratory rat (Rattus) classified in the family Muridae (with the common laboratory mouse, Mus). Antibody reagents that are specific for cotton rat immunoglobulins have not been described. To enhance the usefulness of this model, four immunoglobulins in Sigmodon serum were characterized (IgG1, IgG2, IgA, IgM) and antisera specific for each immunoglobulin were made. Sera from three different species of Sigmodon were examined, S. hispidus (SH), S. arizoni (SA) and S. fulviventer (SF). Although IgA and IgM appeared similar in all three species, the IgG were expressed differently because normal serum levels of IgG2 were deficient in SH when compared with SA and SF and to other rodents. Similarly, IgG2 antibody response to purified protein antigen was deficient in SH although the IgG1 antibody response was superior to that in SF and SA. The three cotton rat species were infected with respiratory syncytial virus, and the kinetics of the antibody response was measured. Neutralizing antibody developed faster and to a higher titre in SH than in SA and SF. The enhanced immunoresponsiveness in SH may compensate for the IgG2 deficiency in SH and these changes appear to be relatively recent events in the evolution of this most populous species of Sigmodon.",,"['Coe, J E', 'Prince, G A']",,,,
,PMC,The transmissible gastroenteritis coronavirus contains a spherical core shell consisting of M and N proteins.,,PMC190415,,,"Coronaviruses are enveloped RNA viruses involved in a variety of pathologies that affect animals and humans. Existing structural models of these viruses propose a helical nucleocapsid under the virion envelope as the unique internal structure. In the present work, we have analyzed the structure of the transmissible gastroenteritis coronavirus. The definition of its organization supports a new structural model for coronaviruses, since a spherical, probably icosahedral, internal core has been characterized. Disruption of these cores induces the release of N-protein-containing helical nucleocapsids. Immunogold mapping and protein analysis of purified cores showed that they consist of M and N proteins, M being the main core shell component. This surprising finding, together with the fact that M protein molecules are also located in the virion envelope, indicates that a reconsideration of the assembly and maturation of coronaviruses, as well as a study of potential M-protein subclasses, is needed.",,"['Risco, C', 'Antón, I M', 'Enjuanes, L', 'Carrascosa, J L']",,,,
,PMC,Proteins encoded by open reading frames 3 and 4 of the genome of Lelystad virus (Arteriviridae) are structural proteins of the virion.,,PMC190414,,,"Four structural proteins of Lelystad virus (Arteriviridae) were recognized by monoclonal antibodies in a Western immunoblotting experiment with purified virus. In addition to the 18-kDa integral membrane protein M and the 15-kDa nucleocapsid protein N, two new structural proteins with molecular masses of 45 to 50 kDa and 31 to 35 kDa, respectively, were detected. Monoclonal antibodies that recognized proteins of 45 to 50 kDa and 31 to 35 kDa immunoprecipitated similar proteins expressed from open reading frames (ORFs) 3 and 4 in baculovirus recombinants, respectively. Therefore, the 45- to 50-kDa protein is encoded by ORF3 and the 31- to 35-kDa protein is encoded by ORF4. Peptide-N-glycosidase F digestion of purified virus reduced the 45- to 50-kDa and 31- to 35-kDa proteins to core proteins of 29 and 16 kDa, respectively, which indicates N glycosylation of these proteins in the virion. Monoclonal antibodies specific for the 31- to 35-kDa protein neutralized Lelystad virus, which indicates that at least part of this protein is exposed at the virion surface. We propose that the 45- to 50-kDa and 31- to 35-kDa structural proteins of Lelystad virus be named GP3 and GP4, to reflect their glycosylation and the ORFs from which they are expressed. Antibodies specific for GP3 and GP4 were detected by a Western immunoblotting assay in swine serum after an infection with Lelystad virus.",,"['van Nieuwstadt, A P', 'Meulenberg, J J', 'van Essen-Zanbergen, A', 'Petersen-den Besten, A', 'Bende, R J', 'Moormann, R J', 'Wensvoort, G']",,,,
,PMC,Characterization of the rubella virus nonstructural protease domain and its cleavage site.,,PMC190407,,,"The region of the rubella virus nonstructural open reading frame that contains the papain-like cysteine protease domain and its cleavage site was expressed with a Sindbis virus vector. Cys-1151 has previously been shown to be required for the activity of the protease (L. D. Marr, C.-Y. Wang, and T. K Frey, Virology 198:586-592, 1994). Here we show that His-1272 is also necessary for protease activity, consistent with the active site of the enzyme being composed of a catalytic dyad consisting of Cys-1151 and His-1272. By means of radiochemical amino acid sequencing, the site in the polyprotein cleaved by the nonstructural protease was found to follow Gly-1300 in the sequence Gly-1299-Gly-1300-Gly-1301. Mutagenesis studies demonstrated that change of Gly-1300 to alanine or valine abrogated cleavage. In contrast, Gly-1299 and Gly-1301 could be changed to alanine with retention of cleavage, but a change to valine abrogated cleavage. Coexpression of a construct that contains a cleavage site mutation (to serve as a protease) together with a construct that contains a protease mutation (to serve as a substrate) failed to reveal trans cleavage. Coexpression of wild-type constructs with protease-mutant constructs also failed to reveal trans cleavage, even after extended in vitro incubation following lysis. These results indicate that the protease functions only in cis, at least under the conditions tested.",,"['Chen, J P', 'Strauss, J H', 'Strauss, E G', 'Frey, T K']",,,,
,PMC,Murine coronavirus membrane fusion is blocked by modification of thiols buried within the spike protein.,,PMC190404,,,"The envelopes of murine hepatitis virus (MHV) particles are studded with glycoprotein spikes that function both to promote virion binding to its cellular receptor and to mediate virion-cell membrane fusion. In this study, the cysteine-rich spikes were subjected to chemical modification to determine whether such structural alterations impact the virus entry process. Ellman reagent, a membrane-impermeant oxidizing agent which reacts with exposed cysteine residues to effect covalent addition of large thionitrobenzoate moieties, was incubated at 37 degrees C with the JHM strain of MHV. Relative to untreated virus, 1 mM Ellman reagent reduced infectivity by 2 log(10) after 1 h. This level of inhibition was not observed at incubation temperatures below 21 degrees C, suggesting that virion surface proteins undergo thermal transitions that expose cysteine residues to modification by the reagent. Quantitative receptor binding and membrane fusion assays were developed and used to show that Ellman reagent specifically inhibited membrane fusion induced by the MHV JHM spike protein. However, this inhibition was strain specific, because the closely related MHV strain A59 was unaffected. To identify the basis for this strain specificity, spike cDNAs were prepared in which portions encoded either JHM or A59 residues. cDNAs were expressed with vaccinia virus vectors and tested for sensitivity to Ellman reagent in the fusion assays. The results revealed a correlation between the severity of inhibition mediated by Ellman reagent and the presence of a JHM-specific cysteine (Cys-1163). Thus, the presence of this cysteine increases the availability of spikes for a thiol modification that ultimately prevents fusion competence.",,"Gallagher, T M",,,,
,PMC,Roles of the sequence encoding tobacco etch virus capsid protein in genome amplification: requirements for the translation process and a cis-active element.,,PMC190370,,,"The roles of the capsid protein (CP) and the CP coding sequence of tobacco etch potyvirus (TEV) in genome amplification were analyzed. A series of frameshift-stop codon mutations that interrupted translation of the CP coding sequence at various positions were introduced into the TEV genome. A series of 3' deletion mutants that lacked the CP coding sequence beyond each of the frameshift-stop codon mutations were also produced. In addition, a series of 5' CP deletion mutants were generated. Amplification of genomes containing either frameshift-stop codon insertions after codons 1, 59, 103, and 138 or genomes containing the corresponding 3' deletions of the CP coding sequence was reduced by 100- to 1,000-fold relative to that of the parental genome in inoculated protoplasts. In contrast, a mutant containing a frameshift-stop codon after CP position 189 was amplified to 27% of the level of the parental virus, but the corresponding 3' deletion mutant lacking codons 190 to 261 was nonviable. Deletion mutants lacking CP codons 2 to 100, 2 to 150, 2 to 189, and 2 to 210 were amplified relatively efficiently in protoplasts, but a deletion mutant lacking codons 2 to 230 was nonviable. None of the amplification-defective frameshift-stop codon or deletion mutants was rescued in transgenic cells expressing TEV CP, although the transgenic CP was able to rescue intercellular movement defects of replication-competent CP mutants. Coupled with previous results, these data led to the conclusions that (i) TEV genome amplification requires translation to a position between CP codons 138 and 189 but does not require the CP product and (ii) the TEV CP coding sequence contains a cis-active RNA element between codons 211 and 246. The implications of these findings on mechanisms of RNA replication and genome evolution are discussed.",,"['Mahajan, S', 'Dolja, V V', 'Carrington, J C']",,,,
,PMC,Equine arteritis virus subgenomic mRNA synthesis: analysis of leader-body junctions and replicative-form RNAs.,,PMC190361,,,"In addition to the genomic RNA, a 3' coterminal nested set of six subgenomic mRNAs is produced in equine arteritis virus (EAV)-infected cells. The seven viral RNAs are also 5' coterminal, since they all contain a 206-nucleotide common leader sequence which is identical to the 5' end of the genome. A conserved penta-nucleotide sequence motif, 5' UCAAC 3', was shown to be present at the junctions between the leader and body sequences in each of the mRNAs. In addition, two alternative junction sites were detected for mRNA 3. Seven replicative-form (RF) RNAs (RFs I to VII), corresponding to the genomic RNA and each of the subgenomic EAV mRNAs, could be prepared from lysates of infected cells. The minus-strand RNA contents of these RF RNAs were analyzed by using an RNase protection assay with an RNA probe containing the mRNA 2 leader-body junction. It was established that RF II contained a negative-stranded copy of mRNA 2, including a complementary leader sequence. The presence of subgenomic minus-strand RNA in RFs is indicative of a function as a transcription template during the production of EAV subgenomic mRNAs.",,"['den Boon, J A', 'Kleijnen, M F', 'Spaan, W J', 'Snijder, E J']",,,,
,PMC,Loss of resistance to murine hepatitis virus strain 3 infection after treatment with corticosteroids is associated with induction of macrophage procoagulant activity.,,PMC190359,,,"Activation of the immune coagulation system has been implicated in the pathogenesis of liver injury following infection of inbred mice with murine hepatitis virus strain 3 (MHV-3). Following MHV-3 infection, macrophages isolated from MHV-3-susceptible and -semisusceptible inbred strains of mice express increased procoagulant activity (PCA), whereas macrophages from resistant strains express no increase in PCA over basal levels. The PCA induced by MHV-3 is a prothrombinase, encoded by the gene Fgl-2, which encodes a fibrinogen-like protein (musfiblp). In this study, MHV-3-resistant A/J mice treated with methylprednisolone prior to infection with MHV-3 developed elevated levels of alanine aminotransferase in serum and died within 10 days of infection, with histological findings of fulminant hepatitis. In vitro, macrophages isolated from A/J mice and pretreated with methylprednisolone produced a marked increase in functional PCA following infection with MHV-3. The PCA was shown to be a prothrombinase by its ability to cleave 125I-prothrombin. Northern blot analysis of RNA transcripts from these macrophages demonstrated increased transcription of the Fgl-2 gene relative to that in macrophages which had not been pretreated with methylprednisolone prior to MHV-3 infection. Methylprednisolone pretreatment of MHV-3-infected macrophages stabilized the Fgl-2 mRNA. Thus, loss of resistance to MHV-3 secondary to methylprednisolone therapy is associated with increased transcription and stability of Fgl-2 mRNA resulting in expression of the Fgl-2 gene product, musfiblp. These results provide further insight into mechanisms of PCA regulation in response to MHV-3 infection in inbred strains of mice.",,"['Fingerote, R J', 'Abecassis, M', 'Phillips, M J', 'Rao, Y S', 'Cole, E H', 'Leibowitz, J', 'Levy, G A']",,,,
,PMC,Identification of overlapping DNA-binding and centromere-targeting domains in the human kinetochore protein CENP-C.,,PMC231353,,,"The kinetochore in eukaryotes serves as the chromosomal site of attachment for microtubules of the mitotic spindle and directs the movements necessary for proper chromosome segregation. In mammalian cells, the kinetochore is a highly differentiated trilaminar structure situated at the surface of the centromeric heterochromatin. CENP-C is a basic, DNA-binding protein that localizes to the inner kinetochore plate, the region that abuts the heterochromatin. Microinjection experiments using antibodies specific for CENP-C have demonstrated that this protein is required for the assembly and/or stability of the kinetochore as well as for a timely transition through mitosis. From these observations, it has been suggested that CENP-C is a structural protein that is involved in the organization or the kinetochore. In this report, we wished to identify and map the functional domains of CENP-C. Analysis of CENP-C truncation mutants expressed in vivo demonstrated that CENP-C possesses an autonomous centromere-targeting domain situated at the central region of the CENP-C polypeptide. Similarly, in vitro assays revealed that a region of CENP-C with the ability to bind DNA is also located at the center of the CENP-C molecule, where it overlaps the centromere-targeting domain.",,"['Yang, C H', 'Tomkiel, J', 'Saitoh, H', 'Johnson, D H', 'Earnshaw, W C']",,,,
,PMC,Ontogeny and immunohistochemical localization of thymus-dependent and thymus-independent RT6+ cells in the rat.,,PMC1861642,,,"RT6 is a cell surface alloantigen that identifies a regulatory subset of peripheral T cells in the rat. Diabetes-prone BB rats are deficient in peripheral RT6+ T cells and develop spontaneous autoimmune insulin-dependent diabetes mellitus. Diabetes-resistant BB rats have normal numbers of RT6+ T cells, and insulin-dependent diabetes mellitus can be induced in these animals by in vivo depletion of peripheral RT6+ cells. Athymic rats are also severely deficient in peripheral RT6+ T cells. Although very different with respect to the peripheral RT6+ cell compartment, normal, athymic, and diabetes-prone BB rats all generate RT6+ intestinal epithelial lymphocytes (IELs). The goal of these studies was to analyze the ontogeny of RT6+ IELs and peripheral lymphoid cells by in situ immunohistochemistry. We observed the following. 1) RT6+ IELs appear before alpha(beta) T-cell-receptor- expressing IELs in diabetes-prone BB, diabetes-resistant BB, and athymic WAG rats. 2) In vivo depletion of peripheral RT6+ T cells in diabetes-resistant BB rats using a cytotoxic monoclonal antibody is not accompanied by depletion of RT6+ IELs. 3) A population of RT6+ T-cell-receptor-negative IELs is present in normal, euthymic diabetes-resistant BB rats, constitutes a larger percentage of the euthymic but lymphopenic diabetes-prone BB rat IEL population, and is the predominant IEL phenotype in athymic WAG rats. These results suggest that RT6+ cells are composed of both thymus-dependent and thymus-independent cell subsets that have different developmental characteristics and may differ in function.",,"['Waite, D. J.', 'Appel, M. C.', 'Handler, E. S.', 'Mordes, J. P.', 'Rossini, A. A.', 'Greiner, D. L.']",,,,
,PMC,"Effect of adoptive transfer of CD4, CD8 and B cells on recovery from MHV3-induced immunodeficiencies.",,PMC1456434,,,"A chronic viral infection can occur when the host fails to mount an effective immune response to clear the virus. Mouse hepatitis virus type 3 (MHV3) appears to be an excellent model for the study of the relationship between viral-induced immunodeficiency and chronic disease development. (C57BL/6 x A/J)F1 mice surviving acute hepatitis develop a chronic disease characterized by T- and B-cell immunodeficiencies, viral persistence in various organs including the brain, spleen and thymus, and death within 3 months postinfection (p.i.). We have reported that T- or B-cell deficiencies, observed in MHV3 chronically infected (C57BL/6 x A/J)F1 mice, can be partially or totally thwarted by adoptive transfer of CD4+, CD8+ and/or B cells, at 15 days p.i. in mice surviving the acute phase of the disease. Adoptive transfer of syngeneic CD4+ and/or CD8+ allowed a partial restoration of the T-cell deficiencies, as characterized by thymic atrophy, decrease in splenic T cells, and in all thymocyte subpopulations. B-cell immunodeficiency, as defined by a decrease in splenic B cells, as well as in the bone marrow pre-B- and B-cell compartments, and the occurrence of abnormally larger forms of bone marrow pre-B and B cells, were partially thwarted by B-cell treatment only. Splenic B cells and the bone marrow B-cell compartment, respectively, returned partially or totally to normal values, whereas the pre-B-cell compartment remained depleted in infected mice treated with B cells. Levels of all immunoglobulin classes returned to normal values in MHV3 chronically infected mice when treated with CD4+ in combination with CD8+ cells. All T- and/or B-cell treatments, however, were sufficient to thwart the process of the chronic disease, and favoured the survival of mice for up to 6 months p.i.",,"['Lamontagne, L', 'Jolicoeur, P', 'Decarie, D', 'Menezes, J']",,,,
,PMC,Experimental genital mycoplasmosis: time of infection influences pregnancy outcome.,,PMC174072,,,"Genital infection of rats with Mycoplasma pulmonis causes adverse pregnancy outcome and can result in in utero spread of infection to the fetus. The current study was designed to determine whether the stage of pregnancy when infection occurs influences pregnancy outcome. Rats were inoculated with 3 X 10(7) CFU of M. pulmonis at 10 days prior to breeding (-10) or at gestational day (gd) 11 or 14 and were necropsied at gd 11, 14, or 18 or within 24 h of parturition (term). Control rats received sterile broth. M. pulmonis was isolated from the placenta, amniotic fluid, or fetal tissues only from rats infected prior to breeding (P < 0.001). All infected rats had significantly more loss of pups than did control rats (P < 0.006), but rats infected prior to breeding or at the beginning of the third trimester (gd 14) were much more likely to have fetal losses. Rats infected in the early second trimester after implantation (gd 11) did not experience severe losses. Litter sizes, total litter weight, and individual pup weight from all infected rats, regardless of gestational stage when infected, were significantly smaller than those of control rats (P < 0.001). On the basis of the results of this study, we conclude that the time of infection plays a major role in determination of pregnancy outcome and spread of infection from the genital tract to the respiratory tract.",,"['Brown, M B', 'Steiner, D A']",,,,
,PMC,Antigenic variability among North American and European strains of porcine reproductive and respiratory syndrome virus as defined by monoclonal antibodies to the matrix protein.,,PMC229047,,,"Two hybridoma cell lines producing monoclonal antibodies (Mabs) to the 19-kDa matrix (M) protein of porcine reproductive and respiratory syndrome virus (PRRSV) were obtained from BALB/c mice that were immunized with a reference Quebec tissue culture-adapted strain (strain IAF-Klop). The polypeptide specificities of the MAbs were determined by immunoblotting and immunoprecipitation tests with concentrated and purified preparations of the virus and by determining their reactivities with the Escherichia coli-expressed gene products of open reading frames 5 to 7. The two anti-M protein MAbs (MAbs IAFK3 and IAFK6) and another MAb (MAb IAFK8) directed to the 15-kDa nucleocapsid (N) protein were devoid of virus-neutralizing activity. A library of four anti-N protein MAbs (MAbs IAFK8, SDOW17, VO17, and EP147) and two anti-M protein MAbs (MAbs IAFK6 and IAFK3) was used to investigate, by an indirect fluorescent-antibody assay, the antigenic diversity of 15 Canadian PRRSV isolates, in comparison with those of the U.S. ATCC VR2332 attenuated vaccine strain and two reference European (Lelystad and Weybridge) PRRSV strains. The North American and European PRRSV isolates tested shared the epitopes recognized by anti-N protein MAbs IAFK8 and SDOW17, but three distinct patterns could be identified on the basis of their reactivities with the other anti-PRRSV MAbs. No reactivity to the anti-M protein MAbs was observed by either European PRRSV isolate or the attenuated U.S. vaccine strain.",,"['Dea, S', 'Gagnon, C A', 'Mardassi, H', 'Milane, G']",,,,
,PMC,Maintenance of pluripotency in mouse embryonic stem cells persistently infected with murine coronavirus.,,PMC190306,,,"A persistently coronavirus-infected embryonic stem (ES) cell line A3/MHV was established by infecting an ES cell line, A3-1, with mouse hepatitis virus type-2. Although almost all A3/MHV cells were found infected, both A3/MHV and A3-1 cells expressed comparable levels of cell surface differentiation markers. In addition, A3/MHV cells retained the ability to form embryoid bodies. These results suggest that persistent coronavirus infection does not affect the differentiation of ES cells.",,"['Okumura, A', 'Machii, K', 'Azuma, S', 'Toyoda, Y', 'Kyuwa, S']",,,,
,PMC,Expression of the recombinant anchorless N-terminal domain of mouse hepatitis virus (MHV) receptor makes hamster of human cells susceptible to MHV infection.,,PMC190304,,,"Mouse hepatitis virus (MHV) receptor, the receptor for the murine coronavirus MHV, was expressed in MHV-resistant hamster and human cells as a series of mutant, recombinant glycoproteins with carboxy-terminal deletions lacking the cytoplasmic tail, transmembrane domain, and various amounts of the immunoglobulin constant-region-like domains. The soluble receptor glycoproteins containing the N-terminal virus-binding domain were released into the supernatant medium and inactivated the infectivity of MHV-A59 virions in a concentration-dependent manner. Surprisingly, some of the anchorless glycoproteins were found on the plasma membranes of transfected cells by flow cytometry, and these cells were rendered susceptible to infection with three strains of MHV. Thus, in the cells in which the anchorless, recombinant receptor glycoprotein is synthesized, some of the protein is bound to an unidentified moiety on the plasma membrane, which allows it to serve as a functional virus receptor.",,"['Dveksler, G S', 'Gagneten, S E', 'Scanga, C A', 'Cardellichio, C B', 'Holmes, K V']",,,,
,PMC,Molecular anatomy of mouse hepatitis virus persistence: coevolution of increased host cell resistance and virus virulence.,,PMC190273,,,"Persistent infection of murine astrocytoma (DBT) cells with mouse hepatitis virus (MHV) has been established. From this in vitro virus-host system, persistence is mediated at the level of cellular MHV receptor (MHVR) expression and increased virus virulence. MHV persistence selects for resistant host cell populations which abate virus replication. Reductions in MHVR expression were significantly associated with increased host resistance, and transfection of MHVR into resistant host cells completely restored the capacity of cells to support efficient replication of MHV strain A59. The emergence of resistant host cells coselected for variant viruses that had increased avidity for MHVR and also recognized different receptors for entry into resistant cells. These data illustrate that MHV persistence in vitro provides a model to identify critical sites of virus-host interaction at the cellular level which are altered during the evolution of host cell resistance to viral infection and the coevolution of virus virulence.",,"['Chen, W', 'Baric, R S']",,,,
,PMC,Tropism of human adenovirus type 5-based vectors in swine and their ability to protect against transmissible gastroenteritis coronavirus.,,PMC190253,,,"The infection of epithelia] swine testicle and intestinal porcine epithelial (IPEC-1) cell lines by adenovirus type 5 (Ad5) has been studied in vitro by using an Ad5-luciferase recombinant containing the firefly luciferase gene as a reporter. Porcine cell lines supported Ad5 replication, showing virus titers, kinetics of virus production, and luciferase expression levels similar to those obtained in human 293 cells, which constitutively express the 5'-end 11% of the Ad5 genome. The tropism of Ad5-based vectors in swine and its ability to induce an efficient immune response against heterologous antigens expressed by foreign genes inserted in these vectors has been determined. Ad5 vectors replicate and express heterologous antigens in porcine lungs and mediastinal and mesenteric lymph nodes. Significant levels of heterologous antigen expression were also demonstrated in the small intestine (jejunum and ileum), but Ad5 replication in this organ was very poor, suggesting that Ad vectors undergo an abortive replication in the porcine small intestine. The tissues infected by Ad5 were dependent on the inoculation route. The oronasal route appeared to be best for inoculation of bronchus-associated lymphoid tissue infection, while the intraperitoneal route was best for gut-associated lymphoid tissue infection. Epithelial cells of bronchioles, macrophages, type II pneumocytes, and follicular dendritic cells were identified as targets for Ad5, while epithelial cells of the intestine were not infected by Ad5. Viruses with a deletion from 79.5 to 84.8 map units in the E3 region, with or without heterologous inserted genes, replicated to lower levels in porcine tissues than did wild-type Ad5. It was also shown that an Ad5 recombinant expressing the four antigenic sites (A, B, C, and D) of transmissible gastroenteritis coronavirus (TGEV) spike protein induced in swine immune responses which neutralized TGEV infectivity. In addition, porcine serum from Ad-TGEV-immune animals provide passive protection when mixed with fully virulent TGEV and orally administered to highly susceptible newborn piglets. These results taken together indicate that swine may be a good animal model for human Ad5 lung infection to aid in the evaluation of candidate adenovirus vaccines and that Ad5 may be suitable as a recombinant viral vaccine or for other applications in swine.",,"['Torres, J M', 'Alonso, C', 'Ortega, A', 'Mittal, S', 'Graham, F', 'Enjuanes, L']",,,,
,PMC,Adenovirus uncoating and nuclear establishment are not affected by weak base amines.,,PMC190220,,,"We have used four established lysosomotropic agents, ammonium chloride, amantadine, chloroquine, and methylamine, to monitor the possible interference with an early low-pH-dependent step during adenovirus replication. Two concentrations of each of the different agents were selected; one was essentially nontoxic to uninfected HeLa cells, and the other resulted in some toxicity as measured by trypan blue staining and by interference with cell monolayer establishment, cell proliferation, and radioisotope labelling. It was separately determined that these concentrations displayed pH-raising effects of the same magnitude as higher concentrations previously used in similar studies. Adenovirus uncoating in vivo, normally reaching its maximum within 1 h after infection, was not affected by any of the agents. The subsequent levels of successful nuclear entry events by the parental genomes were monitored by measuring the extent of transcription of an mRNA species coding for the early 72-kDa DNA-binding protein at 10 to 12 h postinfection. In HeLa, KB, HEp-2, and A549 cells, none of the agents were able to affect the levels of early transcription after administration at the point of infection or at 3 h after infection. The cumulative synthesis of the hexon antigen was assessed late in infection, and inhibitory effects were revealed upon administration of 10, 20, and 40 mM ammonium chloride, 10 mM methylamine, and 0.5 mM amantadine, irrespective of the time point of addition. Ammonium chloride at 5 mM reduced the hexon yield by 20% at the most when added within 50 min after infection. Chloroquine at concentrations of 2.5 and 5 microM specifically reduced the hexon yields by 30 to 40% when administered within the first 50 min of infection. On the basis of the lack of effects of nontoxic concentrations of the four agents on the early virus-cell interactive event of uncoating and the early virus-specified transcription, we conclude that a low-pH-dependent step early in the adenovirus replication cycle is not mandatory for a successful infection.",,"['Rodríguez, E', 'Everitt, E']",,,,
,PMC,"Folding, assembly, and intracellular trafficking of the human immunodeficiency virus type 1 envelope glycoprotein analyzed with monoclonal antibodies recognizing maturational intermediates.",,PMC190213,,,"Monoclonal antibodies (MAbs) that bind linear or conformational epitopes on monomeric or oligomeric human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins were screened for their recognition of maturational intermediates. On the basis of reactivities with gp160 at different times after pulse-labeling, the MAbs were sorted into groups that exhibited binding which was immediate and constant, immediate but transient, delayed, late, or very late. This grouping was consistent with the selectivity of the MAbs for structural features of gp160. Thus, a MAb to the V3 loop reacted with envelope proteins at all times, in accord with the relative conformational independence and accessibility of the epitope. Several MAbs that preferentially react with monomeric gp160 exhibited diminished binding after the pulse. A 10-min tag occurred before gp160 reacted with conformational MAbs that inhibited CD4 binding. The availability of epitopes for other conformational MAbs, including some that react equally with monomeric and oligomeric gp160 and some that react better with oligomeric forms, was half-maximal in 30 min and closely followed the kinetics of gp160 oligomerization. Remarkably, there was a 1- to 2-h delay before gp160 reacted with stringent oligomer-specific MAbs. After 4 h, approximately 20% of the gp160 was recognized by these MAbs. Epitopes recognized by monomerspecific or CD4-blocking MAbs but not by oligomer-dependent MAbs were present on gp160 molecules associated with the molecular chaperone BiP/GRP78. MAbs with a preference for monomers reacted with recombinant or HIV-1 envelope proteins in the endoplasmic reticulum, whereas the oligomer-specific MAbs recognized them in the Golgi complex. Additional information regarding gp160 maturation and intracellular trafficking was obtained by using brefeldin A, dithiothreitol, and a low temperature.",,"['Otteken, A', 'Earl, P L', 'Moss, B']",,,,
,PMC,Development of mucosal and systemic lymphoproliferative responses and protective immunity to human group A rotaviruses in a gnotobiotic pig model.,,PMC170344,,,"Gnotobiotic pigs were orally inoculated with virulent Wa strain (G1P1A[8]) human rotavirus (group 1), attenuated Wa rotavirus (group 2) or diluent (controls) and were challenged with virulent Wa rotavirus 21 days later. On various postinoculation or postchallenge days, virus-specific responses of systemic (blood and spleen) and intestinal (mesenteric lymph node and ileal lamina propria) mononuclear cells (MNC) were assessed by lymphoproliferative assays (LPA). After inoculation, 100% of group 1 pigs and 6% of group 2 pigs shed virus. Diarrhea occurred in 95, 12, and 13% of group 1, group 2, and control pigs, respectively. Only groups 1 and 2 developed virus-specific LPA responses prior to challenge. Group 1 developed significantly greater mean virus-specific LPA responses prior to challenge and showed no significant changes in tissue mean LPA responses postchallenge, and 100% were protected against virulent virus challenge. By comparison, both group 2 and controls had significantly lower LPA responses at challenge and both groups showed significant increases in mean LPA responses postchallenge. Eighty-one percent of group 2 and 100% of control pigs shed challenge virus, and both groups developed diarrhea that was similar in severity postchallenge. The virus-specific LPA responses of blood MNC mirrored those of intestinal MNC, albeit at a reduced level and only at early times postinoculation or postchallenge in all pigs. In a separate study evaluating antibody-secreting-cell responses of these pigs (L. Yuan, L.A. Ward, B.I. Rosen, T.L. To, and L.J. Saif, J. Virol. 70:3075-3083, 1996), we found that the magnitude of a tissue's LPA response positively correlated with the numbers of virus-specific antibody-secreting cells for that tissue, supporting the hypothesis that the LPA assesses T-helper-cell function. The magnitude of LPA responses in systemic and intestinal tissues also strongly correlated with the degree of protective immunity elicited by the inoculum (p = 0.81). We conclude that blood may provide a temporary ""window"" for monitoring intestinal T cells and that the LPA can be used to assess protective immunity to human rotaviruses.",,"['Ward, L A', 'Yuan, L', 'Rosen, B I', 'Tô, T L', 'Saif, L J']",,,,
,PMC,Identification of group B rotaviruses with short genome electropherotypes from adult cows with diarrhea.,,PMC229005,,,"Two field strains (BB-RVLV and KD) of group B rotaviruses from adult dairy cows with diarrhea displayed short genome electropherotypes. Gnotobiotic calves inoculated with fecal filtrates of each group B rotavirus developed diarrhea, and only group B rotaviruses or antigens were detected in the feces by immunoelectron microscopy and in intestinal epithelial cells by immunofluorescent staining, respectively. The feces or intestinal contents of the cows and inoculated calves were negative for group A and C rotaviruses by enzyme-linked immunosorbent assay, immunoelectron microscopy, or cell culture immunofluorescence assays. Comparison of the genome electropherotypes of the calf-passaged BB-RVLV and KD strains with the original samples and reference bovine group A, B, and C rotaviruses revealed conservative of their short-genome electropherotypes and double-stranded RNA migration patterns characteristics of group B rotaviruses. To our knowledge, our previous study (L.J. Saif, K.V. Brock, D.R. Redman, and E.M. Kohler, Vet. Rec. 128:447-449, 1991) and this report are the first description of bovine group B rotaviruses (in a mixed infection with bovine coronavirus or singly in fecal contents) in adult cows with diarrhea and this is the first report of short-genome electropherotypes among group B rotaviruses.",,"['Parwani, A V', 'Lucchelli, A', 'Saif, L J']",,,,
,PMC,"Immunological Instability of Persistent Adenovirus Vectors in the Brain: Peripheral Exposure to Vector Leads to Renewed Inflammation, Reduced Gene Expression, and Demyelination",http://dx.doi.org/10.1523/JNEUROSCI.16-09-03045.1996,PMC6579058,,,"Nonreplicating adenovirus vectors are being developed as vehicles for the delivery of therapeutic genes in vivo. Whereas in many organs an antiviral T cell response eliminates the vector and damages local tissue, when adenovirus vectors are injected into the brain the subsequent immune attack can be ineffective, allowing the vector to persist. In the present study, E1-deleted human adenovirus vectors were injected into the caudate nucleus of rats. Two months later, expression of protein from the vector was still evident and little inflammation was seen. A subcutaneous injection of adenovirus vector at this time, however, led within 2 weeks to severe mononuclear inflammation and microglial activation in the caudate. This caused local demyelination and a decrease in detectable protein expression from the vector. Interestingly, intense microglial activation and numerous lymphocytes and monocytes were also seen in brain areas containing neurons capable of retrogradely transporting the adenovirus vector from the caudate. Control experiments established that this inflammation in distant brain areas was not a nonspecific consequence of degeneration. These experiments demonstrate that although adenovirus vectors can persist in the brain without causing chronic inflammation, they remain the potential target of a damaging cell-mediated immune response brought about by a subsequent peripheral exposure to vector. The finding of lymphocytes in brain areas that project to the caudate further shows that viral antigens that are retrogradely transported by neurons can also be the target of a T cell attack.",,"['Byrnes, Andrew P.', 'MacLaren, Robert E.', 'Charlton, Harry M.']",,,,
,PMC,Cytokine production in the immune response to murine gammaherpesvirus 68.,,PMC190192,,,"Cytokine profiles were determined following intranasal infection of C57BL/6J mice with murine gammaherpesvirus 68 (MHV-68). Spleen, mediastinal, and cervical lymph node cells from infected mice produced high levels of interleukin 6 (IL-6) and gamma interferon (IFN-gamma) and lower levels of IL-2 and IL-10 following in vitro restimulation. Little or no IL-4 or IL-5 was detected. Cytokine production was generally maximal at 10 days after infection, correlating with viral clearance from the lung, although significant levels were seen as early as 3 days after administration of the virus. In vitro infection of naive splenocytes induced B-cell- dependent secretion of IL-6 and IL-10, whereas IFN-gamma and IL-2 were produced only by cells that had been primed in vivo. Depletion of B lymphocytes from primed splenocyte populations did not, however, abrogate IL-6 and IL-10 production. Highly purified immune T cells made IL-6, IL-10. and IFN-gamma following in vitro restimulation with MHV-68. Thus, IL-6 and IL-10 are components of both the acquired and the innate host response. These cytokines have potential roles in the establishment and maintenance of persistent infection.",,"['Sarawar, S R', 'Cardin, R D', 'Brooks, J W', 'Mehrpooya, M', 'Tripp, R A', 'Doherty, P C']",,,,
,PMC,Specificity of the H-2 L(d)-restricted cytotoxic T-lymphocyte response to the mouse hepatitis virus nucleocapsid protein.,,PMC190190,,,"Cytotoxic T lymphocytes provide protection against persistent infection of the central nervous system by the JHM strain of mouse hepatitis virus. In BALB/c (H-2d) mice, the dominant response is directed against an Ld-restricted peptide in the nucleocapsid protein (APTAGAFFF). Characterization of the fine specificity of this response revealed that the predicted anchor residues at positions 2 and 9 were the most critical for class I binding. Amino acids at positions 7 and 8 were identified as T-cell receptor contact residues. Virus-induced cytotoxic T lymphocytes to other Ld motif-containing nucleocapsid peptides were not detected, despite the identification of two epitopes with reduced Ld affinity. These data suggest that mutations within four residues of the dominant epitope could contribute to the persistence of the JHM strain of mouse hepatitis virus.",,"['Bergmann, C C', 'Stohlman, S A']",,,,
,PMC,Systematic and intestinal antibody-secreting cell responses and correlates of protective immunity to human rotavirus in a gnotobiotic pig model of disease.,,PMC190169,,,"Neonatal gnotobiotic pigs orally inoculated with virulent (intestinal-suspension) Wa strain human rotavirus (which mimics human natural infection) developed diarrhea, and most pigs which recovered (87% protection rate) were immune to disease upon homologous virulent virus challenge at postinoculation day (PID) 21. Pigs inoculated with cell culture-attenuated Wa rotavirus (which mimics live oral vaccines) developed subclinical infections and seroconverted but were only partially protected against challenge (33% protection rate). Isotype-specific antibody-secreting cells (ASC were enumerated at selected PID in intestinal (duodenal and ileal lamina propria and mesenteric lymph node [MLN]) and systemic (spleen and blood) lymphoid tissues by using enzyme-linked immunospot assays. At challenge (PID 21), the numbers of virus-specific immunoglobulin A (IgA) ASC, but not IgG ASC, in intestines and blood were significantly greater in virulent-Wa rotavirus-inoculated pigs than in attenuated-Wa rotavirus-inoculated pigs and were correlated (correlation coefficients: for duodenum and ileum, 0.9; for MLN, 0.8; for blood, 0.6) with the degree of protection induced. After challenge, the numbers of IgA and IgG virus-specific ASC and serum-neutralizing antibodies increased significantly in the attenuated-Wa rotavirus-inoculated pigs but not in the virulent-Wa rotavirus-inoculated pigs (except in the spleen and except for IgA ASC in the duodenum). The transient appearance of IgA ASC in the blood mirrored the IgA ASC responses in the gut, albeit at a lower level, suggesting that IgA ASC in the blood of humans could serve as an indicator for IgA ASC responses in the intestine after rotavirus infection. To our knowledge, this is the first report to study and identify intestinal IgA ASC as a correlate of protective active immunity in an animal model of human-rotavirus-induced disease.",,"['Yuan, L', 'Ward, L A', 'Rosen, B I', 'To, T L', 'Saif, L J']",,,,
,PMC,Biophysical characterization of recombinant proteins expressing the leucine zipper-like domain of the human immunodeficiency virus type 1 transmembrane protein gp41.,,PMC190157,,,"Envelope oligomerization is thought to serve several crucial functions during the life cycle of human immunodeficiency virus type 1 (HIV-1). We recently reported that virus entry requires coiled-coil formation of the leucine zipper-like domain of the HIV-1 transmembrane envelope glycoprotein gp41 (C. Wild, T. Oas, C. McDanal, D. Bolognesi, and T. Matthews, Proc. Natl. Acad. Sci. USA 89:10537-10541, 1992; C. Wild, J. W. Dubay, T. Greenwell, T. Baird, Jr., T. G. Oas, C. McDanal, E. Hunter, and T. Matthews, Proc. Natl. Acad. Sci. USA 91:12676-12680, 1994). To determine the oligomeric state mediated by this region of the envelope, we have expressed the zipper motif as a fusion partner with the monomeric maltose-binding protein of Escherichia coli. The biophysical properties of this protein were characterized by velocity and equilibrium sedimentation, size exclusion chromatography, light scattering, and chemical cross-linking analyses. Results indicate that the leucine zipper sequence from HIV-1 is capable of multimerizing much larger and otherwise monomeric proteins into extremely stable tetramers. Recombinant proteins containing an alanine or a serine substitution at a critical isoleucine residue within the zipper region were also generated and similarly analyzed. The alanine- and serine-substituted proteins behaved as tetrameric and monomeric species, respectively, consistent with the influence of these same substitutions on the helical coiled-coil structure of synthetic peptide models. On the basis of these findings, we propose that the fusogenic gp4l structure involves tetramerization of the leucine zipper domain which is situated approximately 30 residues from the N-terminal fusion peptide sequence.",,"['Shugars, D C', 'Wild, C T', 'Greenwell, T K', 'Matthews, T J']",,,,
,PMC,Astrovirus ribosomal frameshifting in an infection-transfection transient expression system.,,PMC190144,,,"Different regions of the human astrovirus frameshift signal were cloned into the rhesus rotavirus VP4 gene and evaluated in an infection-transfection transient expression cell culture system. BHK-21 cells, infected with a vaccinia virus that expresses T7 RNA polymerase (vTF7-3), were transfected with the various astrovirus-VP4 constructs. All constructs were driven by a T7 promoter and contained an internal ribosome entry site. Frameshifted and nonframeshifted protein products were immunoprecipitated with VP4 amino- and carboxy-terminal-specific monoclonal antibodies, and their ratios were determined by PhosphorImager analysis. The efficiency of frameshifting was 25 to 28%, significantly greater than the 5 to 7% efficiency reported previously in a cell-free translation system. Coupling of transcription and translation in a cell-free system yielded frameshifting efficiencies threefold greater than that of the uncoupled in vitro system. The presence of the shifty heptamer was an absolute requirement for frameshifting in both cell-free and intact-cell systems, while deletion of the potential downstream pseudoknot region did not affect the efficiency of frameshifting.",,"['Lewis, T L', 'Matsui, S M']",,,,
,PMC,The UCUAAAC promoter motif is not required for high-frequency leader recombination in bovine coronavirus defective interfering RNA.,,PMC190128,,,"The 65-nucleotide leader on the cloned bovine coronavirus defective interfering (DI) RNA, when marked by mutations, has been shown to rapidly convert to the wild-type leader of the helper virus following DI RNA transfection into helper virus-infected cells. A model of leader-primed transcription in which free leader supplied in trans by the helper virus interacts by way of its flanking 5'UCUAAAC3' sequence element with the 3'-proximal 3'AGAUUUG5' promoter on the DI RNA minus strand to prime RNA replication has been used to explain this phenomenon. To test this model, the UCUAAAC element which occurs only once in the BCV 5' untranslated region was either deleted or completely substituted in input DI RNA template, and evidence of leader conversion was sought. In both cases, leader conversion occurred rapidly, indicating that this element is not required on input RNA for the conversion event. Substitution mutations mapped the crossover region to a 24-nucleotide segment that begins within the UCUAAAC sequence and extends downstream. Although structure probing of the bovine coronavirus 5' untranslated region indicated that the UCUAAAC element is in the loop of a prominent stem and thus theoretically available for base pair-directed priming, no evidence of an unattached leader early in infection that might have served as a primer for transcription was found by RNase protection studies. These results together suggest that leader conversion on the DI RNA 5' terminus is not guided by the UCUAAAC element and might arise instead from a high-frequency, region-specific, homologous recombination event perhaps during minus-strand synthesis rather than by leader priming during plus-strand synthesis.",,"['Chang, R Y', 'Krishnan, R', 'Brian, D A']",,,,
,PMC,Nucleocapsid-independent assembly of coronavirus-like particles by co-expression of viral envelope protein genes.,,PMC450121,,,"Budding of enveloped viruses has been shown to be driven by interactions between a nucleocapsid and a proteolipid membrane. By contrast, we here describe the assembly of viral envelopes independent of a nucleocapsid. Membrane particles containing coronaviral envelope proteins were assembled in and released from animal cells co-expressing these proteins' genes from transfected plasmids. Of the three viral membrane proteins only two were required for particle formation, the membrane glycoprotein (M) and the small envelope protein (E). The spike (S) protein was dispensable but was incorporated when present. Importantly, the nucleocapsid protein (N) was neither required not taken into the particles when present. The E protein, recently recognized to be a structural protein, was shown to be an integral membrane protein. The envelope vesicles were found by immunogold labelling and electron microscopy to form a homogeneous population of spherical particles indistinguishable from authentic coronavirions in size (approximately 100 nm in diameter) and shape. They were less dense than virions and sedimented slightly slower than virions in sucrose velocity gradients. The nucleocapsid-independent formation of apparently bona fide viral envelopes represents a novel mode of virus assembly.",,"['Vennema, H', 'Godeke, G J', 'Rossen, J W', 'Voorhout, W F', 'Horzinek, M C', 'Opstelten, D J', 'Rottier, P J']",,,,
,PMC,"Parasite prevalence in free-ranging farm cats, Felis silvestris catus.",,PMC2271614,,,"No animals tested were positive for feline leukemia virus antigen and Chlamydia psittaci antibodies, but all were positive for antibodies to feline calicivirus (FCV), feline herpesvirus 1 (FHV1) and rotavirus. They had antibodies to feline parvovirus (96%), feline coronavirus (84% and cowpox virus (2%). Antibody to feline immunodeficiency virus (FIV) was found in 53% of animals, which were less likely to be infected with Haemobartonella felis, and had higher FHV antibody titres than cats without FIV. FCV was isolated from 51% cats and FHV1 and feline reovirus each from 4%. H. felis was present in 42% of animals, and antibody to Toxoplasma gondii in 62%. Clinical abnormality had a significant association with FIV and feline calicivirus infections, but sex, age, social status and feeding group had no significant association with prevalence of any parasites. Toxocara cati and Toxascaris leonina eggs were found, respectively, in 91% and 82% of animals tested.",,"['Yamaguchi, N.', 'Macdonald, D. W.', 'Passanisi, W. C.', 'Harbour, D. A.', 'Hopper, C. D.']",,,,
,PMC,"Sport, Exercise, and the Common Cold",,PMC1318446,,,"Upper respiratory illness may cause more disability among athletes than all other diseases combined. This paper presents the essential epidemiology, risks of infection, and transmission features of upper respiratory illness. Those who provide health care for athletes must understand the subsequent implications of an upper respiratory illness on sport performance and should be familiar with participation and clinical management guidelines for athletes with an upper respiratory illness. The literature suggests that regular, rigorous exercise increases both the incidence and severity of upper respiratory illness, yet the immune system appears to have a distinct level at which moderate exercise promotes optimum health. Although research indicates that upper respiratory illness infections are surprisingly reluctant transmitters, upper respiratory illness transmission may escalate during winter sports seasons. The impact of upper respiratory illness on selected pulmonary, cardiac, and skeletal muscle functions may lead to illness complications in athletes, and sport performance during illness may also decline. Athletes should monitor symptoms, adjust training schedules, and rest during an upper respiratory illness.",,"['Weidner, Thomas G.', 'Sevier, Thomas L.']",,,,
,PMC,Analysis of the receptor-binding site of murine coronavirus spike protein.,,PMC190114,,,"It has been found that a domain composed of 330 amino acids of the N terminus of murine coronavirus spike protein [S1N(330)] is involved in receptor-binding activity (H. Kubo, Y.K. Yamada, and F. Taguchi, J. Virol. 68:5403-5410, 1994). To delineate the amino acid sequences involved in receptor-binding activity, we have compared the S1N(330) proteins of seven different mouse hepatitis virus MHV strains that are able to utilize the MHV receptor protein. Three conserved regions (sites I, II, and III) were found to consist of more than 10 identical amino acids, and they were analyzed for receptor-binding activity by site-directed mutagenesis. S1N(330) with a substitution at position 62 from the N terminus of S1 in region I and that with substitutions at positions 212, 214, and 216 in region II showed no receptor-binding activity. The S1N(330) mutants without receptor-binding activity were not able to prevent virus binding to the receptor. These results suggest that the receptor-binding site on S1N(330) is composed of regions located apart from each other in the protein's primary structure, in which Thr at position 62 as well as amino acids located at positions 212, 214, and 216 are particularly important.",,"['Suzuki, H', 'Taguchi, F']",,,,
,PMC,cis Requirement for N-specific protein sequence in bovine coronavirus defective interfering RNA replication.,,PMC190059,,,"A naturally occurring 2.2-kb defective interfering (DI) RNA of the bovine coronavirus, structurally a simple fusion of the genomic termini, contains a single contiguous open reading frame (ORF) or 1.7 kb composed of the 5'-terminal 288 nucleotides of polymerase gene 1a and all 1,344 nucleotides of the nucleocapsid protein (N) gene. The ORF must remain open throughout most of its sequence for replication to occur. To determine the qualitative importance of the N portion of the chimeric ORF in DI RNA replication, transcripts of mutated reporter-containing constructs were tested for replication in helper virus-infected cells. It was determined that the N ORF could not be replaced by the naturally occurring internal I protein ORF, accomplished by deleting the first base in the N start codon which leads to a +1 frameshift, nor could it be replaced by the chloramphenicol acetyltransferase ORF. Furthermore, 3'-terminal truncations of the N gene leaving less than 85% of its total length were likewise not tolerated. Small in-frame deletions and in-frame foreign sequence insertions of up to 99 nucleotides within certain regions of the N ORF were tolerated, however, but the rate of DI RNA accumulation in these cases was lower. These results indicate that there is a requirement for translation of most if not all of the N protein in cis for optimal replication of the bovine coronavirus DI RNA and suggest that a similar requirement may exist for viral genome replication.",,"['Chang, R Y', 'Brian, D A']",,,,
,PMC,Identification of domains in rubella virus genomic RNA and capsid protein necessary for specific interaction.,,PMC190057,,,"In rubella virus-infected cells, genomic 40S and subgenomic 24S RNAs are present in the cytoplasm of infected cells. However, encapsidation by rubella virus capsid protein is specific for 40S genomic RNA. As a first step toward understanding the assembly of rubella virus nucleocapsid at the molecular level, the interaction between capsid protein and genomic RNA was studied by Northwestern (RNA-protein) blot analysis. RNA probes prepared by in vitro transcription were used to localize the RNA sequence that participates in binding to the capsid protein. We have identified a 29-nucleotide RNA sequence (nucleotides 347 to 375) that is essential for the binding. By using overlapping synthetic peptides of capsid protein, a peptide domain (residues 28 to 56) that displays specific RNA-binding activity of capsid protein has been located. This result suggests that the specific recognition of viral RNA during rubella virus assembly involves, at least in part, the nucleocapsid protein.",,"['Liu, Z', 'Yang, D', 'Qiu, Z', 'Lim, K T', 'Chong, P', 'Gillam, S']",,,,
,PMC,Pneumocystis carinii in a patient with pulmonary sarcoidosis and idiopathic CD4+ T lymphocytopenia.,,PMC1090687,,,A case of pulmonary sarcoidosis and idiopathic CD4+ T lymphocytopenia is reported. Pneumocystis carinii was detected in the bronchoalveolar lavage fluid of a young homosexual man who was asymptomatic without any evidence of congenital or acquired immunodeficiency but with a low CD4+ cell count. A clinical and histological diagnosis of pulmonary sarcoidosis was made. During follow up the patient had oral candidiasis and a CD4+ cell count persistently below 300/microliters. This case is highly suggestive of concurrent pulmonary sarcoidosis and idiopathic CD4+ T lymphocytopenia.,,"['Sinicco, A.', 'Maiello, A.', 'Raiteri, R.', 'Sciandra, M.', 'Dassio, G.', 'Zamprogna, C.', 'Mecozzi, B.']",,,,
,PMC,Reading two bases twice: mammalian antizyme frameshifting in yeast.,,PMC450040,,,"Programmed translational frameshifting is essential for the expression of mammalian ornithine decarboxylase antizyme, a protein involved in the regulation of intracellular polyamines. A cassette containing antizyme frameshift signals is found to direct high-level (16%) frameshifting in yeast, Saccharomyces cerevisiae. In contrast to +1 frameshifting in the mammalian system, in yeast the same frame is reached by -2 frameshifting. Two bases are read twice. The -2 frameshifting is likely to be mediated by slippage of mRNA and re-pairing with the tRNA in the P-site. The downstream pseudoknot stimulates frameshifting by 30-fold compared with 2.5-fold in reticulocyte lysates. When the length of the spacer between the shift site and the pseudoknot is extended by three nucleotides, +1 and -2 frameshifting become equal.",,"['Matsufuji, S', 'Matsufuji, T', 'Wills, N M', 'Gesteland, R F', 'Atkins, J F']",,,,
,PMC,Z-membranes: artificial organelles for overexpressing recombinant integral membrane proteins.,,PMC39938,,,We have expressed a fusion protein formed between the avian infectious bronchitis virus M protein and the bacterial enzyme beta-glucuronidase in transgenic tobacco cells. Electron microscope images of such cells demonstrate that overexpression of this fusion protein gives rise to a type of endoplasmic reticulum membrane domain in which adjacent membranes become zippered together apparently as a consequence of the oligomerizing action of beta-glucuronidase. These zippered (Z-) membranes lack markers of the endoplasmic reticulum (NADH cytochrome c reductase and ribosomes) and accumulate in the cells in the form of multilayered scroll-like structures (up to 2 micrometers in diameter; 20-50 per cell) without affecting plant growth. The discovery of Z-membranes has broad implications for biology and biotechnology in that they provide a means for accumulating large quantities of recombinant membrane proteins within discrete domains of native membranes.,,"['Gong, F C', 'Giddings, T H', 'Meehl, J B', 'Staehelin, L A', 'Galbraith, D W']",,,,
,PMC,Peptides from conserved regions of paramyxovirus fusion (F) proteins are potent inhibitors of viral fusion.,,PMC39932,,,"The synthetic peptides DP-107 and DP-178 (T-20), derived from separate domains within the human immunodeficiency virus type 1 (HIV-1) transmembrane (TM) protein, gp4l, are stable and potent inhibitors of HIV-1 infection and fusion. Using a computer searching strategy (computerized antiviral searching technology, C.A.S.T.) based on the predicted secondary structure of DP-107 and DP-178 (T-20), we have identified conserved heptad repeat domains analogous to the DP-107 and DP-178 regions of HIV-1 gp41 within the glycoproteins of other fusogenic viruses. Here we report on antiviral peptides derived from three representative paramyxoviruses, respiratory syncytial virus (RSV), human parainfluenza virus type 3 (HPIV-3), and measles virus (MV). We screened crude preparations of synthetic 35-residue peptides, scanning the DP-178-like domains, in antiviral assays. Peptide preparations demonstrating antiviral activity were purified and tested for their ability to block syncytium formation. Representative DP-178-like peptides from each paramyxovirus blocked homologous virus-mediated syncytium formation and exhibited EC50 values in the range 0.015-0.250 microM. Moreover, these peptides were highly selective for the virus of origin. Identification of biologically active peptides derived from domains within paramyxovirus F1 proteins analogous to the DP-178 domain of HIV-1 gp4l is compelling evidence for equivalent structural and functional features between retroviral and paramyxoviral fusion proteins. These antiviral peptides provide a novel approach to the development of targeted therapies for paramyxovirus infections.",,"['Lambert, D M', 'Barney, S', 'Lambert, A L', 'Guthrie, K', 'Medinas, R', 'Davis, D E', 'Bucy, T', 'Erickson, J', 'Merutka, G', 'Petteway, S R']",,,,
,PMC,"Growth of influenza A virus in primary, differentiated epithelial cells derived from adenoids.",,PMC190039,,,"Epithelial cells of adenoid origin were grown in tissue culture to examine viral replication in cells that are the primary target of many human pathogens. These cells remained highly differentiated, with subpopulations of cells which retained active ciliary motility and others which demonstrated specialized secretory functions. The epithelial cells were permissive for growth of influenza A virus. Primary respiratory epithelial cells provide a model system for examining virulence, cell tropism, and receptors which replicate in the nasopharynx.",,"['Endo, Y', 'Carroll, K N', 'Ikizler, M R', 'Wright, P F']",,,,
,PMC,Capsid coding sequence is required for efficient replication of human rhinovirus 14 RNA.,,PMC190023,,,"Mechanisms by which the plus-sense RNA genomes of picornaviruses are replicated remain poorly defined, but existing models do not suggest a role for sequences encoding the capsid proteins. However, candidate RNA replicons (delta P1 beta gal and delta P1Luc), representing the sequence of human rhinovirus 14 virus (HRV-14) with reporter protein sequences (beta-galactosidase or luciferase, respectively) replacing most of the P1 capsid-coding region, failed to replicate in transfected H1-HeLa cells despite efficient primary cleavage of the polyprotein. To determine which P1 sequences might be required for RNA replication, HRV-14 mutants in which segments of the P1 region were removed to frame from the genome were constructed. Mutants with deletions involving the 5'proximal 1,489 nucleotides of the P1 region replicated efficiently, while those with deletions involving the 3' 1,079 nucleotides did not. Reintroduction of the 3' P1 sequence into the nonreplicating delta P1Luc construct resulted in a new candidate replicon, delta P1Luc/VP3, which replicated well and expressed luciferase efficiently. Capsid proteins provided in trans by helper virus failed to rescue the nonreplicating delta P1Luc genome but were able to package the larger-than-genome-length delta P1Luc/VP3 replicon. Thus, a 3'-distal P1 capsid-coding sequence has a previously unrecognized cis-active function related to replication of HRV-14 RNA.",,"['McKnight, K L', 'Lemon, S M']",,,,
,PMC,Characterization in vitro of an autocatalytic processing activity associated with the predicted 3C-like proteinase domain of the coronavirus avian infectious bronchitis virus.,,PMC190021,,,"A region of the infectious bronchitis virus (IBV) genome between nucleotide positions 8693 and 10927 which encodes the predicted 3C-like proteinase (3CLP) domain and several potential cleavage sites has been clones into a T7 transcription vector. In vitro translation of synthetic transcripts generated from this plasmid was not accompanied by detectable processing activity of the nascent polypeptide unless the translation was carried out in the presence of microsomal membrane preparations. The processed products so obtained closely resembled in size those expected from cleavage at predicted glutamine-serine (Q/S) dipeptides and included a protein with a size of 35 kDa (p35) that corresponds to the predicted size of 3CLP. Efficient processing was dependent on the presence of membranes during translation; processing was found to occur when microsomes were added posttranslationally, but only after extended periods of incubation. C-terminal deletion analysis of the encoded polyprotein fragment revealed that cleavage activity was dependent on the presence of most but not all of the downstream and adjacent hydrophobic region MP2. Dysfunctional mutagenesis of the putative active-site cysteine residue of 3CLP to either serine or alanine resulted in polypeptides that were impaired for processing, while mutagenesis at the predicted Q/S release sites implicated them in the release of the p35 protein. Processed products of the wild-type protein were active in trans cleavage assays, which were used to demonstrate that the IBV 3CLP is sensitive to inhibition by both serine and cysteine protease class-specific inhibitors. These data reveal the identity of the IBV 3C-like proteinase, which exhibits characteristics in common with the 3C proteinases of picornaviruses.",,"['Tibbles, K W', 'Brierley, I', 'Cavanagh, D', 'Brown, T D']",,,,
,PMC,Inhibition of Nef- and phorbol ester-induced CD4 degradation by macrolide antibiotics.,,PMC189974,,,"Human immunodeficiency virus type 1 (HIV-1) is the causative agent of AIDS. The simian immunodeficiency virus (SIV) causes a similar syndrome in macaques. The product of the nef gene of SIV has been shown to be important for virus replication and disease progression in vivo. In vitro, both SIV and HIV Nef downregulate surface expression of CD4 and accelerate total CD4 turnover. The mechanism by which Nef downregulates CD4 has not been established. A current model suggests that Nef enhances cell surface CD4 endocytosis and degradation in lysosomes. However, this was recently challenged when CD4 was found to accumulate in early endosomes of cells expressing Nef. Because inhibition of Nef function might halt virus replication and disease progression, we tested two macrolide antibiotics for their ability to inhibit Nef function. Concanamycin B (ConB) and bafilomycin A1 (BFLA1) are specific inhibitors of acidification of cell endosomes and lysosomes and, unlike other inhibitors, do not affect transport. Although ConB (25 nM) and BFLA1 (100 nM) blocked phorbol myristate acetate- and Nef-induced CD4 degradation in human monocyte U937 cells, CD4 surface expression was not recovered. Instead, CD4 accumulated in lysosomes. To determine if Nef is directly responsible for CD4 degradation or if they bind to each other in a manner similar to Vpu, transcripts of human CD4 and HIV-1 nef were cotranslated in vitro. Our results indicate that under our experimental conditions, Nef does not affect CD4 stability and does not associate with CD4 in this in vitro system. Our data suggest that (i) CD4 downregulation by Nef results in degradation of CD4 in lysosomes, (ii) inhibition of CD4 degradation by macrolide antibiotics does not restore surface expression, and (iii) the inhibition of CD4 expression by Nef appears to be indirect and is likely to involve cellular factors.",,"['Luo, T', 'Anderson, S J', 'Garcia, J V']",,,,
,PMC,Double-stranded RNA viruses of Saccharomyces cerevisiae.,,PMC239427,,,,,"Wickner, R B",,,,
,PMC,Programmed translational frameshifting.,,PMC239420,,,,,"Farabaugh, P J",,,,
,PMC,Interleukin-11: stimulation in vivo and in vitro by respiratory viruses and induction of airways hyperresponsiveness.,,PMC507136,,,"To address the role of IL-11 in viral airways dysfunction, we determined whether infectious agents that exacerbate asthma stimulate stromal cell IL-11 production, determined whether IL-11 could be detected at sites of viral infection and evaluated the effects of IL-11 on airway physiology. Respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV3), and rhinovirus (RV) 14 were potent stimulators while cytomegalovirus and adenovirus only weakly stimulated and herpes simplex virus type 2 and bacteria did not stimulate IL-11 elaboration. IL-11 was not detected or barely detected in nasal aspirates from children without, but was detected in aspirates from children with viral upper respiratory tract infections. The levels of IL-11 were highest in patients with clinically detectable wheezing. IL-11 also caused nonspecific airways hyperresponsiveness in BALB/c mice. These studies demonstrate that three major causes of viral-induced asthma, RSV, RV, and PIV, in contrast to other viruses and bacteria, share the ability to induce stromal cell IL-11 production. They also demonstrate that IL-11 can be detected in vivo during viral respiratory infections, that the presence of IL-11 correlates with clinical bronchospasm and that IL-11 is a potent inducer of airways hyperresponsiveness. IL-11 may be an important mediator in viral airways disorders.",,"['Einarsson, O', 'Geba, G P', 'Zhu, Z', 'Landry, M', 'Elias, J A']",,,,
,PMC,Impact of influenza and respiratory syncytial virus on mortality in England and Wales from January 1975 to December 1990.,,PMC2271234,,,"The effects of influenza A and B and RSV on mortality in England and Wales were assessed by regression analysis for the period 1975-90. Morbidity data from sentinel practices were used to calculate 4-weekly rates of aggregated upper respiratory tract infections (URTI); PHLS laboratory reports were used as indices of infection, and 4-weekly death rates from all causes, excluding childbirths, were used to study relationships with mortality. Deaths correlated strongly with influenza A and B reports, temperature, and interactions between aggregated URTI and temperature, and RSV outbreaks and temperature. Estimates of 'seasonal' 4-weekly mortality associated with URTI were made by substituting into primary regression models the mean of annual trough consultation rates for aggregated URTI and baseline values for RSV and influenza. Peak 4-weekly mortality associated with URTIs was estimated at c. 24000 and c. 28000 during combined influenza and RSV epidemics of 1975-6 and 1989-90 respectively. Secondary regression analysis was carried out with the estimated 'seasonal' 4-weekly deaths associated with URTI as dependent variable and laboratory data as regressors. Estimated excess mortality associated with influenza was considerable even during years without major epidemics. Overall during the 15 winters the estimated mortality associated with RSV was 60-80% more than that associated with influenza. The modelling permits only a crude estimate of RSV associated mortality. None the less it suggests that RSV is an important cause of winter mortality.",,"Nicholson, K. G.",,,,
,PMC,A 5'-proximal RNA sequence of murine coronavirus as a potential initiation site for genomic-length mRNA transcription.,,PMC189870,,,"Coronavirus transcription is a discontinuous process, involving interactions between a trans-acting leader and the intergenic transcription initiation sequences. A 9-nucleotide (nt) sequence (UUUAUAAAC), which is located immediately downstream of the leader at the 5' terminus of the mouse hepatitis virus (MHV) genomic RNA, contains a sequence resembling the consensus intergenic sequence (UCUAAAC). It has been shown previously that the presence of the 9-nt sequence facilitates leader RNA switching and may enhance subgenomic mRNA transcription. It is unclear how the 9-nt sequence exerts these functions. In this study, we inserted the 9-nt sequence into a defective interfering (DI) RNA reporter system and demonstrated that mRNA transcription could be initiated from the 9-nt sequence almost as efficiently as from the intergenic sequence between genes 6 and 7. Sequence analysis of the mRNAs showed that the 9-nt sequence served as a site of fusion between the leaders and mRNA. The transcription initiation function of the 9-nt sequence could not be substituted by other 5'-terminal sequences. When the entire 5'-terminal sequence, including four copies of the UCUAA sequence plus the 9-nt sequence, was present, transcription could be initiated from any of the UCUAA copies or the 9-nt sequence, resulting in different copy numbers of the UCUAA sequence and the deletion of the 9-nt sequence in some mRNAs. All of these heterogeneous RNA species were also detected from the 5'-terminal region of the viral genomic-length RNA in MHV-infected cells. These results thus suggest tha the heterogeneity of the copy number of UCUAA sequences at the 5' end, the deletion of the 9-nt sequence in viral and DI RNAs, and the leader RNA switching are the results of transcriptional initiation from the 9-nt site. They also show that an mRNA species (mRNA 1) that lacks the 9-nt sequence can be synthesized during MHV infection. Therefore, MHV genomic RNA replication and mRNA 1 transcription may be distinguishable.",,"['Zhang, X', 'Lai, M M']",,,,
,PMC,The signal recognition particle receptor alpha subunit assembles co-translationally on the endoplasmic reticulum membrane during an mRNA-encoded translation pause in vitro.,,PMC449929,,,"Many proteins, including the alpha subunit of the signal recognition particle receptor (SR alpha), are targeted within the cell by poorly defined mechanisms. A 140 residue N-terminal domain of SR alpha targets and anchors the polypeptide to the endoplasmic reticulum membrane by a mechanism independent of the pathway involving the signal recognition particle. To investigate the mechanism of membrane anchoring, translation pause sites on the SR alpha mRNA were used to examine the targeting of translation intermediates. A strong pause site at nucleotide 507 of the mRNA open reading frame corresponded with the shortest nascent SR alpha polypeptide able to assemble on membranes. An mRNA sequence at this pause site that resembles a class of viral -1 frameshift sequences caused translation pausing when transferred into another mRNA context. Site-directed mutagenesis of the mRNA greatly reduced translation pausing without altering the polypeptide sequence, demonstrating unambiguously a role for this mRNA sequence in translation pausing. SR alpha polypeptides synthesized from the non-pausing mRNA were impaired in co-translational membrane anchoring. Furthermore, co-translational membrane assembly of SR alpha appears to anchor polysomes translating SR alpha to membranes.",,"['Young, J C', 'Andrews, D W']",,,,
,PMC,Nondisruptive detection of activity of catabolic promoters of Pseudomonas putida with an antigenic surface reporter system.,,PMC167789,,,"A simple procedure to detect the switching on and off of catabolic promoters of Pseudomonas putida, at the level of single cells based on the immunodetection of a reporter epitope expressed on the surface of bacterial cells, has been developed. To do this, the antigenic sequence Asp-Leu-Pro-Pro-Asn-Ser-Asp-Val-Val-Asp, from a coronavirus, was inserted genetically in the permissive site around amino acid position 153 of the LamB protein (maltose and lambda phage receptor) of Escherichia coli. When the hybrid lamB gene is transcribed, the epitope becomes presented on the surface of the bacterial cells in a configuration available to specific antibodies. To validate this notion in nonenteric bacteria, the expression and correct processing of LamB were confirmed by coupling the lamB gene to the salicylate-responsive Psa1 promoter of the NAH7 (naphthalene degradation) plasmid in Pseudomonas putida. Subsequently, a hybrid lamB gene carrying the sequence of the coronavirus antigen was placed downstream of the m-toluate-responsive Pm promoter of the TOL (toluene degradation) plasmid. Exposure of the epitope on the Pseudomonas cell surface was monitored through fluorescence of whole cells treated with a monoclonal antibody against the heterologous antigen. Fluorescence emission was dependent on the presence of m-toluate in the medium, thus permitting detection of the Pm promoter switching on by simple optical inspection of individual cells, even in situations when these are a very minor component of a complex bacterial community.",,"['Cebolla, A', 'Guzmán, C', 'de Lorenzo, V']",,,,
,PMC,QUIZ CORNER,,PMC1576599,,,,,,,,,
,PMC,Infections and antibiotic resistance in nursing homes.,,PMC172878,,,"Infections occur frequently in nursing home residents. The most common infections are pneumonia, urinary tract infection, and skin and soft tissue infection. Aging-associated physiologic and pathologic changes, functional disability, institutionalization, and invasive devices all contribute to the high occurrence of infection. Antimicrobial agent use in nursing homes is intense and usually empiric. All of these factors contribute to the increasing frequency of antimicrobial agent-resistant organisms in nursing homes. Programs that will limit the emergence and impact of antimicrobial resistance and infections in nursing homes need to be developed.",,"['Nicolle, L E', 'Strausbaugh, L J', 'Garibaldi, R A']",,,,
,PMC,Identification of a molecule uniquely expressed on a gamma/delta TCR+ subset within bovine intestinal intraepithelial lymphocytes.,,PMC1383969,,,"An antigen has been identified, recognized by a novel monoclonal antibody CC45, which is expressed by a subpopulation of bovine gamma/delta T-cell receptor-positive (gamma/delta TCR+) T cells restricted in their distribution to the intestinal epithelium. This subset of intestinal intraepithelial lymphocytes (iIEL) which represented 8-29% of gamma/delta TCR+ T cells in the gut epithelium expressed CD45, CD3 and L-selectin; most of these cells were CD2- and CD8-. Electron microscopic studies of CC45+ cells revealed that they were large mononuclear leucocytes containing numerous mitochondria and smooth vesicles; a proportion of these contained membrane-bound dense granules. Immunoprecipitation of 125I-labelled iIEL analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis under reducing and non-reducing conditions revealed polypeptides of 60,000 and 200,000 molecular weights, respectively indicating that the antigen, which appears distinct from molecules described in other species, is expressed on the cell surface as a complex.",,"['Parsons, K R', 'Sopp, P', 'Jones, B V', 'Bland, P', 'Howard, C J']",,,,
,PMC,Role of virus-specific CD4+ cytotoxic T cells in recovery from mouse hepatitis virus infection.,,PMC1383965,,,"Macrophages and T lymphocytes play an important role in recovery from viral infections. During mouse hepatitis virus (MHV-A59) infection, a clear virus-specific class II-restricted cytotoxic T-cell response is generated. Transfer of these CD4+ cytotoxic T cells (CTL) into naive mice protects against a lethal challenge with MHV. However, their in vivo antiviral effector mechanism is not yet clear. To further investigate a possible effector mechanism, we studied the effect of adoptive transfer of CD4+ CTL on virus localization in spleen and liver. We showed that adoptive transfer of virus-specific T cells does not affect localization of MHV-A59 in different macrophage subsets. Interestingly, a rapid and large infiltrate of CD4+ T cells in and around MHV-A59-infected foci in the liver was observed early in infection, whereas no CD8+ T cells were detectable. Moreover, transfer of virus-specific T cells resulted in significantly decreased viral titres in the liver and spleen and a marginally increased anti-MHV-A59 IgM production. These results imply an important role for virus-specific CD4+ CTL in elimination of infectious MHV-A59 and induction of an effective immune response in the absence of CD8+ CTL.",,"['Wijburg, O L', 'Heemskerk, M H', 'Sanders, A', 'Boog, C J', 'Van Rooijen, N']",,,,
,PMC,In vivo restoration of biologically active 3' ends of virus-associated RNAs by nonhomologous RNA recombination and replacement of a terminal motif.,,PMC189836,,,"Sequences at the 3' ends of plus-strand RNA viruses and their associated subviral RNAs are important cis elements for the synthesis of minus strands in vivo and in vitro. All RNAs associated with turnip crinkle virus (TCV), including the genomic RNA (4,054 bases) and satellite RNAs (sat-RNAs) such as sat-RNA D (194 bases), terminate with the motif CCUGCCC. While investigating the ability of in vivo-generated recombinants between sat-RNA D and TCV to be amplified in plants, we discovered that sat-RNA D, although truncated by as many as 15 bases in the chimeric molecules, was released from the chimeric transcripts and amplified to high levels. The ""new"" sat-RNA D molecules nearly all terminated with the motif (C1-2)UG(C1-3) (which may begin with 1 or 2 cytosines and end with 1, 2, or 3 cytosines), which was similar or identical to the natural sat-RNA D 3' end. The new sat-RNA D also contained between 1 and 22 bases of heterogeneous sequence upstream from the terminal motif, which, in some cases, was apparently derived from internal regions of either the plus or minus strand of the TCV genomic RNA. Since most of these internal genomic RNA sequences within TCV were not adjacent to (C1-2)UG(C1-3), at least two steps were required to produce new sat-RNA D 3' ends: nonhomologous recombination with the TCV genomic RNA followed by the addition or modification of the terminus to generate the (C1-2)UG(C1-3) motif.",,"['Carpenter, C D', 'Simon, A E']",,,,
,PMC,Homologous RNA recombination in brome mosaic virus: AU-rich sequences decrease the accuracy of crossovers.,,PMC189831,,,"Brome mosaic virus, a tripartite positive-stranded RNA virus of plants, was used for the determination of sequence requirements of imprecise (aberrant) homologous recombination. A 23-nucleotide (nt) region that included a 6-nt UUAAAA sequence (designated the AU sequence) common between wild-type RNA2 and mutant RNA3 supported both precise and imprecise homologous recombination, though the latter occurred with lower frequency. Doubling the length of the 6-nt AU sequence in RNA3 increased the incidence of imprecise crossovers by nearly threefold. Duplication or triplication of the length of the AU sequence in both RNA2 and RNA3 further raised the frequency of imprecise crossovers. The majority of imprecise crosses were located within or close to the extended AU sequence. Imprecise recombinants contained either nucleotide substitutions, nontemplated nucleotides, small deletions, or small sequence duplications within the region of crossovers. Deletion of the AU sequence from the homologous region in RNA3 resulted in the accumulation of only precise homologous recombinants. Our results provide experimental evidence that AU sequences can facilitate the formation of imprecise homologous recombinants. The generation of small additions or deletions can be explained by a misannealing mechanism within the AU sequences, while replicase errors during RNA copying might explain the occurrence of nucleotide substitutions or nontemplated nucleotides.",,"['Nagy, P D', 'Bujarski, J J']",,,,
,PMC,Saccharomyces cerevisiae L-BC double-stranded RNA virus replicase recognizes the L-A positive-strand RNA 3' end.,,PMC189816,,,"L-A and L-BC are two double-stranded RNA viruses present in almost all strains of Saccharomyces cerevisiae. L-A, the major species, has been extensively characterized with in vitro systems established, but little is known about L-BC. Here we report in vitro template-dependent transcription, replication, and RNA recognition activities of L-BC. The L-BC replicase activity converts positive, single-stranded RNA to double-stranded RNA by synthesis of the complementary RNA strand. Although L-A and L-BC do not interact in vivo, in vitro L-BC virions can replicate the positive, single-stranded RNA of L-A and its satellite, M1, with the same 3' end sequence and stem-loop requirements shown by L-A virions for its own template. However, the L-BC virions do not recognize the internal replication enhancer of the L-A positive strand. In a direct comparison of L-A and L-BC virions, each preferentially recognizes its own RNA for binding, replication, and transcription. These results suggest a close evolutionary relation of these two viruses, consistent with their RNA-dependent RNA polymerase sequence similarities.",,"['Ribas, J C', 'Wickner, R B']",,,,
,PMC,A pregnancy-specific glycoprotein is expressed in the brain and serves as a receptor for mouse hepatitis virus.,,PMC40303,,,"Mouse hepatitis virus (MHV), a murine coronavirus known to cause encephalitis and demyelination, uses murine homologues of carcinoembryonic antigens as receptors. However, the expression of these receptors is extremely low in the brain. By low-stringency screening of a mouse brain cDNA library, we have identified a member of the pregnancy-specific glycoprotein (PSG) subgroup of the carcinoembryonic antigen gene family. Unlike other PSG that are expressed in the placenta, it is expressed predominantly in the brain. Transfection of the cDNA into COS-7 cells, which lack a functional MHV receptor, conferred susceptibility to infection by some MHV strains, including A59, MHV-2, and MHV-3, but not JHM. Thus, this is a virus strain-specific receptor. The detection of multiple receptors for MHV suggests the flexibility of this virus in receptor utilization. The identification of this virus in receptor utilization. The identification of a PSG predominantly expressed in the brain also expands the potential functions of these molecules.",,"['Chen, D S', 'Asanaka, M', 'Yokomori, K', 'Wang, F', 'Hwang, S B', 'Li, H P', 'Lai, M M']",,,,
,PMC,Unique features of internal initiation of hepatitis C virus RNA translation.,,PMC394721,,,"The question of whether hepatitis C virus (HCV) RNA is translated by a mechanism of internal ribosome entry has been examined by testing whether insertion of HCV sequences between the two cistrons of a dicistronic mRNA promotes translation of the downstream cistron in rabbit reticulocyte lysates. Deletion analysis showed that efficient internal initiation required a segment of the HCV genome extending from about nucleotides 40-370 and that deletions from the 3'-end of this element were highly deleterious. As the authentic initiation codon for HCV polyprotein synthesis is at nucleotide 342, this demonstrates that, besides 5'-UTR sequences, a short length of HCV coding sequences is required for internal initiation. This finding was confirmed in transfection assays of BT7-H cells and was shown to be independent of the nature of the downstream reporter cistron. The strong requirement for coding sequences is in sharp contrast to internal initiation of picornavirus RNA translation. As a probable correlate with this, it was also found that the efficiency of internal initiation was only marginally compromised when the authentic initiation codon was mutated to a non-AUG codon, again in sharp contrast with the picornaviruses. The finding that coding sequences are required for internal initiation has important implications for the design of experiments to test for internal initiation of translation of cellular mRNAs.",,"['Reynolds, J E', 'Kaminski, A', 'Kettinen, H J', 'Grace, K', 'Clarke, B E', 'Carroll, A R', 'Rowlands, D J', 'Jackson, R J']",,,,
,PMC,Virology research and virulent human pandemics.,,PMC2271593,,,"The possibility that a devastating human pandemic could arise, causing massive loss of human life, is discussed. Such a major threat to the human species is likely to be a virus, and would spread by the respiratory route. It need not necessarily cause massive loss of life, but if it caused serious illness or incapacity it would still have a major impact. A possible source is from an existing respiratory pathogen, but it would more probably arise from an infection that is maintained in an arthropod or vertebrate host, but which at present either does not infect humans, or if it does it fails to be effectively transmitted between them. More research should therefore focus on the pathogenetic factors and the viral determinants that promote respiratory transmission.",,"Mims, C. A.",,,,
,PMC,Sexual and in-contact transmission of asinine strain of equine arteritis virus among donkeys.,,PMC228691,,,"Two in a group of five naturally seropositive donkey stallions were found to shed equine arteritis virus (EAV) in their semen as demonstrated by virus isolation. Direct intramuscular inoculation of sonicated semen from one virus-shedding stallion (S3) caused clinical disease in two donkeys from which virus was recovered and in which seroconversion was detected. Sexual transmission was confirmed in two mares mated to S3 when after a febrile response during which EAV was isolated from huffy coats and nasal and ocular exudates, both mares were found to have seroconverted. In-contact transmission in a susceptible stallion was demonstrated after its exposure to a sexually infected mare. The 3' end of the asinine virus was amplified directly from donkey semen with EAV-specific primers, and its nucleotide sequence was found to be homologous to that of the prototype Bucyrus virus isolated from horses. These results indicate that EAV and its disease transmission are analogous in donkeys and horses.",,"['Paweska, J T', 'Volkmann, D H', 'Barnard, B J', 'Chirnside, E D']",,,,
,PMC,Isolation of coronaviruses antigenically indistinguishable from bovine coronavirus from wild ruminants with diarrhea.,,PMC228685,,,"Diarrheal feces from three sambar deer and one waterbuck in a wild animal habitat and one white-tailed deer on a wildlife farm in Ohio contained coronavirus particles which were agglutinated by antiserum to bovine coronavirus (BCV) in immune electron microscopy. Three coronavirus strains were isolated in human rectal tumor cells from the feces of the sambar and white-tailed deer and the waterbuck, respectively. Hemagglutination, receptor-destroying enzyme activity, indirect immunofluorescence, hemagglutination inhibition, virus neutralization, and Western blot (immunoblot) tests showed close biological and antigenic relationships among the isolates and with selected BCV strains. Gnotobiotic and colostrum-deprived calves inoculated with each of these isolates developed diarrhea and shed coronavirus in their feces and from their nasal passages. In a serological survey of coronavirus infections among wild deer, 8.7 and 6.6% of sera from mule deer in Wyoming and from white-tailed deer in Ohio, respectively, were seropositive against both of the isolates and selected BCV isolates by indirect immunofluorescence tests. These results confirm the existence of coronaviruses in wild ruminants and suggest that these species may harbor coronavirus strains transmissible to cattle.",,"['Tsunemitsu, H', 'el-Kanawati, Z R', 'Smith, D R', 'Reed, H H', 'Saif, L J']",,,,
,PMC,CD8+ T-cell epitopes within the surface glycoprotein of a neurotropic coronavirus and correlation with pathogenicity.,,PMC189767,,,"CD8+ T cells with cytotoxic activity against the surface glycoprotein (S) of mouse hepatitis virus, strain JHM, have been identified in the central nervous system (CNS) of both acutely and chronically infected C57BL/6 mice. In this report, two specific epitopes recognized by these CNS-derived cells were identified, using a panel of peptides chosen because they conformed to the allele-specific binding motif for MHC class I H-2Kb and H-2Db. The active peptides encompassed residues 510 to 518 (CSLWNGPHL, H-2Db) and 598 to 605 (RCQIFANI, H-2Kb). Both epitopes are located within the region of the S protein previously shown to be prone to deletion after passage in animals. These deleted strains are generally less neurovirulent than the wild-type virus but still are able to cause demyelination. Since C57BL/6 mice become persistently infected more commonly than many other strains of mice, these data are consistent with a role for CD8+ T-cell escape mutants in the pathogenesis of the demyelinating disease. This is the first report of CD8+ T-cell epitope localization within the S protein, the protein most strongly implicated thus far in pathogenesis in the host.",,"['Castro, R F', 'Perlman, S']",,,,
,PMC,Susceptibility and signs associated with mouse adenovirus type 1 infection of adult outbred Swiss mice.,,PMC189759,,,"Adult Swiss outbred mice from two sources had a nearly 6,000-fold difference in susceptibility to mouse adenovirus type 1-induced disease. This difference was not attributable to differential organ tropism. Signs associated with mouse adenovirus type 1 infection that have not been previously reported are described at the clinical, gross pathological, and histological levels.",,"['Kring, S C', 'King, C S', 'Spindler, K R']",,,,
,PMC,Envelopment of varicella-zoster virus: targeting of viral glycoproteins to the trans-Golgi network.,,PMC189740,,,"Previous studies suggested that varicella-zoster virus derives its final envelope from the trans-Golgi network (TGN) and that envelope glycoproteins (gps) are transported to the TGN independently of nucleocapsids. We tested the hypothesis that gpI is targeted to the TGN as a result of a signal sequence or patch encoded in its cytosolic domain. cDNAs encoding gpI wild type (wt) and a truncated mutant gpI(trc) lacking transmembrane and cytosolic domains were cloned by using the PCR. Cells transfected with cDNA encoding gpI(wt) or gpI(trc) synthesized and N glycosylated the proteins. gpI(wt) accumulated in the TGN, some reached the plasmalemma, but none was secreted. In contrast, gpI(trc) was retained and probably degraded in the endoplasmic reticulum; none was found on cell surfaces, but some was secreted. The distribution of gpI(trc) was not affected by deletion of potential glycosylation sites. To locate a potential gpI-targeting sequence, cells were transfected with cDNA encoding chimeric proteins in which the ectodomain of a plasmalemmal marker, the interleukin-2 receptor (tac), was fused to different domains of gpI. A chimeric protein in which tac was fused with the transmembrane and cytoplasmic domains of gpI was targeted to the TGN. In contrast, a chimeric protein in which tac was fused only with the gpI transmembrane domain passed through the TGN and concentrated in endosomes. We conclude that gpI is targeted to the TGN as a result of a targeting sequence or patch in its cytosolic domain.",,"['Zhu, Z', 'Gershon, M D', 'Hao, Y', 'Ambron, R T', 'Gabel, C A', 'Gershon, A A']",,,,
,PMC,Regulation of coronavirus mRNA transcription.,,PMC189729,,,"Coronaviruses synthesize a nested set of six to eight subgenomic (sg) mRNAs in infected cells. These mRNAs are produced in different, but constant, molar ratios. It is unclear which factors control the different levels of sg mRNAs. To determine whether the intergenic sequence (IS) involved in sg mRNA synthesis could affect the transcription efficiencies of other ISs and in this way regulate transcription levels, we inserted multiple ISs at different positions into a mouse hepatitis virus defective interfering RNA. Quantitation of the sg RNAs produced by identical ISs in different sequence contexts led to the following conclusions: (i) transcription efficiency depends on the location of the IS in the defective interfering virus genome, (ii) downstream ISs have a negative effect on transcription levels from upstream ISs, and (iii) upstream ISs have little or no effect on downstream ISs. The observation that a downstream IS downregulates the amounts of sg RNA produced by an upstream IS explains why the smaller sg RNAs are, in general, produced in larger quantities than the larger sg RNAs. Our data are consistent with coronavirus transcription models in which ISs attenuate transcription. In these models, larger sg RNAs are synthesized in smaller amounts because they encounter more attenuating ISs during their synthesis.",,"['van Marle, G', 'Luytjes, W', 'van der Most, R G', 'van der Straaten, T', 'Spaan, W J']",,,,
,PMC,Mouse adenovirus type 1 causes a fatal hemorrhagic encephalomyelitis in adult C57BL/6 but not BALB/c mice.,,PMC189708,,,"Mouse adenovirus type 1 (MAV-1) produces a lethal disease in newborn or suckling mice characterized by infectious virus and viral lesions in multiple organs. Previous reports of MAV-1 infection of adult mice generally described serologic evidence of infection without morbidity or mortality. However, our current results demonstrate that MAV-1 causes a fatal illness in adult C57BL/6(B6) mice (50% lethal dose, [LD50], 10(3.0) PFU) but not in adult BALB/c mice at all of the doses tested (LD50, > or = 10(5.0) PFU). Adult (BALB/c x B6)F1 mice were intermediately susceptible (LD50, 10(4.5) PFU). Clinically, the sensitive B6 mice showed symptoms of acute central nervous system (CNS) disease, including tremors, seizures, ataxia, and paralysis. Light microscopic examination of CNS tissue from the B6 animals revealed petechial hemorrhages, edema, neovascularization, and mild inflammation in the brain and spinal cord. Analysis by electron microscopy showed evidence of inflammation, such as activated microglia, as well as swollen astrocytic endfeet and perivascular lipid deposition indicative of blood-brain barrier dysfunction. Outside of the CNS, the only significant pathological findings were foci of cytolysis in the splenic white pulp. Assessment of viral replication from multiple tissues was performed by using RNase protection assays with an antisense MAV-1 early region 1a probe. The greatest amounts of viral mRNA in MAV-1-infected B6 animals were located in the brain and spinal cord. Less viral message was detected in the spleen, lungs, and heart. No viral mRNA was detected in BALB/c mouse tissue, with the exception of low levels in the heart. Viral titers of organ tissues were also determined and were concordant with RNase protection findings on the brain and spinal cord but failed to demonstrate significant infectious virus in additional organs. Our experiments demonstrate that MAV-1 has a striking tropism for the CNS that is strain dependent, and this provides an informative in vivo model for the study of adenoviral pathogenesis.",,"['Guida, J D', 'Fejer, G', 'Pirofski, L A', 'Brosnan, C F', 'Horwitz, M S']",,,,
,PMC,Function of a 5'-end genomic RNA mutation that evolves during persistent mouse hepatitis virus infection in vitro.,,PMC189691,,,"Persistently infected cultures of DBT cells were established with mouse hepatitis virus strain A59 (MHV-A59), and the evolution of the MHV leader RNA and 5' end of the genome was studied through 119 days postinfection. Sequence analysis of independent clones demonstrated an overall mutation frequency approaching 1.2 x 10(-3) to 6.7 x 10(-3). The rate of fixation of mutations was about 1.2 x 10(-5) to 7.6 x 10(-5) per nucleotide (nt) per day. In contrast to finding in bovine coronavirus, the MHV leader RNA sequences were extremely stable and did not evolve significantly during persistent infection. Rather, a 5' untranslated region (UTR) A-to-G mutation at nt 77 in the genomic RNA emerged by day 56 and accumulated until 50 to 80% of the genome-length molecules retained the mutation by 119 days postinfection. Although other 5'-end mutations were noted, only the nt 77 mutation was significantly associated with viral persistence in vitro. Mutations were also found in the 5' end of the p28 coding region, but no specific alterations accumulated in genome-length molecules through 119 days postinfection. The 5' UTR nt 77 mutation resulted in an 18-amino-acid open reading frame (ORF) upstream of the ORF 1a AUG start site. By in vitro translation assays, the small ORF was not translated into detectable product but the mutation significantly enhanced translation of the downstream p28 ORF about 2.5-fold. Variant viruses, containing either the nt 77 A-to-G mutation (V16-ATG+) or wild-type sequences at this locus (V1-ATG-), were isolated at 119 days postinfection. The variant viruses replicated more efficiently than wild-type virus and were extremely cytolytic in DBT cells, suggesting that the A-to-G mutation did not encode a nonlytic or attenuated phenotype. Consistent with the in vitro translation results, a significant increase (approximately 3.5-fold) in p28 expression was also observed with the mutant virus (V16-ATG+) in DBT cells compared with that in wild-type controls. These data indicate that MHV persistence was significantly associated with mutation and evolution in the 5'-end UTR which enhanced the translation of the ORF 1a and potentially ORF 1b polyproteins which function in virus transcription and replication.",,"['Chen, W', 'Baric, R S']",,,,
,PMC,Genesis of Sindbis virus by in vivo recombination of nonreplicative RNA precursors.,,PMC189675,,,"Genetically engineered RNA transcripts coding for various Sindbis virus (SIN) genes were used to study structure and sequence requirements of RNA recombination in BHK cells. Three different groups of RNA transcripts were made: (i) RNAs which retain the ability to replicate and which carry sequences coding for either viral polymerase or viral structural proteins; (ii) RNAs which lack the complete 3' end of the SIN genome and thus are incapable of replicating; and (iii) RNAs which lack the complete 5' end of the SIN genome and also are incapable of replicating. BHK cells were transfected with specific combinations of these precursor RNAs, and virus production and RNA synthetic abilities of the released virus were determined. We demonstrate in vivo generation of infectious SIN by fusion of (i) replicative RNAs to nonreplicative RNAs and (ii) two nonreplicative RNA precursors. Both homologous and nonhomologous types of recombinations were observed. In the homologous type of recombination, a 694-nucleotide overlap at the crossover region of the first pair of precursors resulted in the addition of an A residue converting the UAG stop codon of nonstructural protein P4 to a UAA stop codon. In the nonhomologous type of recombination, the crossover sites contained deletion of up to 76 nucleotides from one of the precursors and complete preservation of junction sequence from the other precursor. This is also the first report that a cytoplasmic RNA virus can be generated from biologically nonreplicative RNA precursors. These results have implications for initiation of viral RNA synthesis and recombination between RNA viral genomes in general. We favor template switching as a mechanism for the fusion events described here and suggest inclusion of polymerase scanning of diverse nonreplicative RNAs as an inherent feature of the copy choice model of RNA recombination. Very importantly, the facile nature of RNA recombination occurring between nonreplicative RNA precursors should speed up the production and analysis of targeted mutants of SIN and possibly other RNA viruses.",,"['Raju, R', 'Subramaniam, S V', 'Hajjou, M']",,,,
,PMC,Genetic elements of plant viruses as tools for genetic engineering.,,PMC239387,,,"Viruses have developed successful strategies for propagation at the expense of their host cells. Efficient gene expression, genome multiplication, and invasion of the host are enabled by virus-encoded genetic elements, many of which are well characterized. Sequences derived from plant DNA and RNA viruses can be used to control expression of other genes in vivo. The main groups of plant virus genetic elements useful in genetic engineering are reviewed, including the signals for DNA-dependent and RNA-dependent RNA synthesis, sequences on the virus mRNAs that enable translational control, and sequences that control processing and intracellular sorting of virus proteins. Use of plant viruses as extrachromosomal expression vectors is also discussed, along with the issue of their stability.",,"['Mushegian, A R', 'Shepherd, R J']",,,,
,PMC,QUIZ CORNER,,PMC1687021,,,,,,,,,
,PMC,The S2 subunit of the murine coronavirus spike protein is not involved in receptor binding.,,PMC189649,,,"The receptor-binding capacity of the S2 subunit of the murine coronavirus S protein was examined by testing the inhibition of virus-receptor binding. Sp-4 virus and S1N(330), which consists of the N-terminal 330 amino acids of the S1 protein, both of which exhibited receptor-binding capacity, were able to prevent the binding of cl-2 virus to the receptor, while the mutant protein S1N(330)-159, which failed to bind to the receptor protein, and S2TM-, which lacks the transmembrane and cytoplasmic domains normally existing in the S2, were unable to prevent the binding of cl-2. By using cultured DBT cells, it was revealed that the infection of cells by cl-2 virus was significantly inhibited by S1N(330) but not by S2TM-. These results indicate that the S2 protein is not involved in the receptor binding of murine coronaviruses.",,"Taguchi, F",,,,
,PMC,3C-like protease of rabbit hemorrhagic disease virus: identification of cleavage sites in the ORF1 polyprotein and analysis of cleavage specificity.,,PMC189637,,,"Rabbit hemorrhagic disease virus, a positive-stranded RNA virus of the family Caliciviridae, encodes a trypsin-like cysteine protease as part of a large polyprotein. Upon expression in Escherichia coli, the protease releases itself from larger precursors by proteolytic cleavages at its N and C termini. Both cleavage sites were determined by N-terminal sequence analysis of the cleavage products. Cleavage at the N terminus of the protease occurred with high efficiency at an EG dipeptide at positions 1108 and 1109. Cleavage at the C terminus of the protease occurred with low efficiency at an ET dipeptide at positions 1251 and 1252. To study the cleavage specificity of the protease, amino acid substitutions were introduced at the P2, P1, and P1' positions at the cleavage site at the N-terminal boundary of the protease. This analysis showed that the amino acid at the P1 position is the most important determinant for substrate recognition. Only glutamic acid, glutamine, and aspartic acid were tolerated at this position. At the P1' position, glycine, serine, and alanine were the preferred substrates of the protease, but a number of amino acids with larger side chains were also tolerated. Substitutions at the P2 position had only little effect on the cleavage efficiency. Cell-free expression of the C-terminal half of the ORF1 polyprotein showed that the protease catalyzes cleavage at the junction of the RNA polymerase and the capsid protein. An EG dipeptide at positions 1767 and 1768 was identified as the putative cleavage site. Our data show that rabbit hemorrhagic disease virus encodes a trypsin-like cysteine protease that is similar to 3C proteases with regard to function and specificity but is more similar to 2A proteases with regard to size.",,"['Wirblich, C', 'Sibilia, M', 'Boniotti, M B', 'Rossi, C', 'Thiel, H J', 'Meyers, G']",,,,
,PMC,"Characterization of ts 16, a temperature-sensitive mutant of vaccinia virus.",,PMC189627,,,"We have characterized a temperature-sensitive mutant of vaccinia virus, ts16, originally isolated by Condit et al. (Virology 128:429-443, 1983), at the permissive and nonpermissive temperatures. In a previous study by Kane and Shuman (J. Virol 67:2689-2698, 1993), the mutation of ts16 was mapped to the I7 gene, encoding a 47-kDa protein that shows partial homology to the type II topoisomerase of Saccharomyces cerevisiae. The present study extends previous electron microscopy analysis, showing that in BSC40 cells infected with ts16 at the restrictive temperature (40 degrees C), the assembly was arrested at a stage between the spherical immature virus and the intracellular mature virus (IMV). In thawed cryosections, a number of the major proteins normally found in the IMV were subsequently localized to these mutant particles. By using sucrose density gradients, the ts16 particles were purified from cells infected at the permissive and nonpermissive temperatures. These were analyzed by immunogold labelling and negative-staining electron microscopy, and their protein composition was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. While the ts16 virus particles made at the permissive temperature appeared to have a protein pattern identical to that of wild-type IMV, in the mutant particles the three core proteins, p4a, p4b, and 28K, were not proteolytically processed. Consistent with previous data the sucrose-purified particles could be labelled with [3H]thymidine. In addition, anti-DNA labelling on thawed cryosections suggested that most of the mutant particles had taken up DNA. On thawed cryosections of cells infected at the permissive temperature, antibodies to I7 labelled the virus factories, the immature viruses, and the IMVs, while under restrictive conditions these structures were labelled much less, if at all. Surprisingly, however, by Western blotting (immunoblotting) the I7 protein was present in similar amounts in the defective particles and in the IMVs isolated at the permissive temperature. Finally, our data suggest that at the nonpermissive temperature the assembly of ts16 is irreversibly arrested in a stage at which the DNA is in the process of entering but before the particle has completely sealed, as monitored by protease experiments.",,"['Ericsson, M', 'Cudmore, S', 'Shuman, S', 'Condit, R C', 'Griffiths, G', 'Locker, J K']",,,,
,PMC,Fast and high-affinity binding of B-lymphotropic papovavirus to human B-lymphoma cell lines.,,PMC189591,,,"Binding of B-lymphotropic papovavirus (LPV) to host cells differing in susceptibility to viral infection was determined by a newly established, direct, nonradioactive virus binding assay, which allows quantitative description of the binding characteristics by receptor saturation and Scatchard analysis. LPV binding to the highly susceptible human B-lymphoma cell line BJA-B K88 is specific, saturable, and noncooperative. Binding occurs very fast, with an association rate constant (k1) of 6.7 x 10(7) M-1s-1, and is of high affinity, with a dissociation constant (Kd) of 2.9 x 10(-12) M; and the virus-receptor complex is stable, with a half life of 70 min. The binding affinities of receptors on four other highly, moderately, or weakly susceptible human B-lymphoma cell lines were similar, with up to twofold variation around a mean Kd value of 3 x 10(-12) M, suggesting the presence of the same LPV receptor on all of these cell lines. This view is further supported by the finding that in all cases a terminal sialic acid is necessary for LPV binding. Tunicamycin has been shown to drastically induce LPV susceptibility and LPV binding in weakly and moderately susceptible B-lymphoma cell lines (O.T. Keppler, M. Herrmann, M. Oppenländer, W. Meschede, and M. Pawlita, J. Virol. 68:6933-6939, 1994). The hypothesis that the constitutively expressed and tunicamycin-induced LPV receptors are identical is strengthened by our finding that both receptor types displayed the same high affinity. LPV susceptibility of different B-lymphoma cell lines was correlated with receptor number but not with receptor affinity. The numbers of receptors per cell on highly and moderately susceptible cell lines ranged from 2,000 to 400 and were directly proportional to LPV susceptibility. This indicates that the number of high-affinity receptors per cell is a key regulating factor for the LPV host range.",,"['Herrmann, M', 'Oppenländer, M', 'Pawlita, M']",,,,
,PMC,Ribosomal frameshifting during translation of measles virus P protein mRNA is capable of directing synthesis of a unique protein.,,PMC189585,,,"Members of the Paramyxoviridae family utilize a variety of different strategies to increase coding capacity within their P cistrons. Translation initiation at alternative 5'-proximal AUG codons is used by measles virus (MV) to express the virus-specific P and C proteins from overlapping reading frames on their mRNAs. Additional species of mRNAs are transcribed from the MV P cistron by the insertion of extra nontemplated G residues at a specific site within the P transcript. Addition of only a single nontemplated G residue results in the expression of the V protein, which contains a unique carboxyl terminus. We have used an Escherichia coli system to express MV P cistron-related mRNAs and proteins. We have found that ribosomal frameshifting on the MV P protein mRNA is capable of generating a previously unrecognized P cistron-encoded protein that we have designated R. Some ribosomes which have initiated translation of the P protein mRNA use the sequence TCC CCG AG (24 nucleotides upstream of the V protein stop codon) to slip into the -1 reading frame, thus translating the sequence as TC CCC GAG. The resulting R protein terminates five codons downstream of the frameshift site at the V protein stop codon. We have gone on to use a chloramphenicol acetyltransferase reporter system to demonstrate that this MV-specific sequence is capable of directing frameshifting during in vivo translation in eukaryotic cells. Analysis of immunoprecipitated proteins from MV-infected cells by two-dimensional gel electrophoresis allowed detection of a protein species consistent with R protein in MV-infected cells. Quantitation of this protein species allowed a rough estimation of frameshift frequency of approximately 1.8%. Significant stimulation of ribosomal frameshift frequency at this locus of the MV P mRNA was mediated by a downstream stimulator element which, although not yet fully defined, appeared to be neither a conventional stem-loop nor an RNA pseudoknot structure.",,"['Liston, P', 'Briedis, D J']",,,,
,PMC,An investigation of the role of transmembrane domains in Golgi protein retention.,,PMC394566,,,"The single transmembrane domains (TMDs) of the resident glycosylation enzymes of the Golgi apparatus are involved in preventing these proteins moving beyond the Golgi. It has been proposed that either the TMDs associate, resulting in the formation of large oligomers of Golgi enzymes, or that they mediate the lateral segregation of the enzymes between lipid microdomains. Evidence for either type of interaction has been sought by examining the retention of sialyltransferase (ST), an enzyme of the mammalian trans Golgi. No evidence could be obtained for specific interactions or 'kin recognition' between ST and other proteins of the trans Golgi. Moreover, it is shown that the previously described kin recognition between enzymes of the medial Golgi involves the lumenal portions of these proteins rather than their TMDs. To investigate further the role of the ST TMD, the effects on Golgi retention of various alterations in the TMD were examined. The addition or removal of residues showed that the efficiency of retention of ST is related to TMD length. Moreover, when a type I plasma membrane protein was expressed with a synthetic TMD of 23 leucines it appeared on the cell surface, but when the TMD was shortened to 17 leucines accumulation in the Golgi was observed. These observations are more consistent with lipid-based sorting of ST TMD, but they also allow for reconciliation with the kin recognition model which appears to act on sequences outside of the TMD.",,"Munro, S",,,,
,PMC,Detection of toxin genes in Escherichia coli isolated from normal dogs and dogs with diarrhea.,,PMC1263780,,,"The etiology of acute, nonviral diarrhea in dogs is poorly understood. Enterotoxigenic and verotoxigenic Escherichia coli are causal agents of diarrhea in humans, pigs, and cattle, but the association of these toxigenic E. coli with diarrhea in dogs has not been explored to a significant extent. In this study, DNA hybridization and PCR amplification were used to identify the frequency with which the genes for E. coli enterotoxins (STap, STb, and LTI) and verotoxins (VT1 and VT2) occur in association with diarrhea in dogs. Genes for VT1 (8.9%), VT2 (22.2%), STa (26.7%), and STb (4.4%) were identified in E. coli cultured from feces of 20 of 45 dogs (44.4%) with diarrhea. Genes for VT2, STa, and STb were not identified in feces from normal dogs. Genes for VT1 were observed in similar proportions in fecal samples from diarrheic (8.9%) and normal (12.3%) dogs. Heat labile enterotoxin (LTI) was not detected in fecal samples from either diarrheic or normal dogs. Our results suggest that heat stable enterotoxins and VT2 may be causally associated with diarrhea in dogs. Dogs appear to be able to carry VT1-producing E. coli without showing overt signs of disease.",,"['Hammermueller, J', 'Kruth, S', 'Prescott, J', 'Gyles, C']",,,,
,PMC,QUIZ CORNER,,PMC1687116,,,,,,,,,
,PMC,Expression of interferon-gamma receptors on murine oligodendrocytes and its regulation by cytokines and mitogens.,,PMC1384003,,,"Interferon-gamma (IFN-gamma) is a cytokine known to exert an important immunological role on astrocytes and oligodendrocytes. As a receptor for IFN-gamma has been demonstrated on murine astrocytes, we have searched for a specific receptor on the cell surface of pure mouse oligodendrocytes maintained in tissue culture. Using recombinant murine IFN-gamma labelled with 125I, we have established the basic physicochemical parameters of the binding. A single receptor was found with a Kd of 1 x 10(-9) M. The number of receptors per cell was 3000-4000 and its molecular weight, as determined by cross-linking experiments, is 87,000. The binding of IFN-gamma to its oligodendrocyte receptor is saturable, specific and temperature-dependent. The receptor-IFN-gamma complex is quickly endocytosed at 37 degrees (the half-time of maximal internalization is around 1 min). Some cytokines, such as interleukin-1 alpha and interleukin-6, up-regulated the expression of the oligodendrocyte receptor, but others, such as tumour necrosis factor-alpha, did not. A dramatic increase in receptor expression is induced by lipopolysaccharide but it is not detectable after treatment with concanavalin A.",,"['Torres, C', 'Aránguez, I', 'Rubio, N']",,,,
,PMC,Nocardia species as an etiologic agent in Parkinson's disease: serological testing in a case-control study.,,PMC228573,,,"To test the hypothesis that Nocardia spp. may be an etiologic factor in Parkinson's disease (PD), we used a serodiagnostic panel to determine if PD patients had antibodies specific for Nocardia spp. To validate the serological test panel, sera from healthy volunteers and from patients with culture-proven nocardiosis (n = 307) were compared in part 1 of the study. The sensitivity of the panel was 88% for detection of culture-proven nocardial infections, and specificity was 85% (excluding cross-reactive leprosy cases). In part 2, no difference in seropositivity was found when PD patients were compared with their age- and gender-matched controls (n = 140). We found a high exposure rate of humans to nocardial antigens, especially among men and older individuals. Our results offer no support to the hypothesis that Nocardia spp. are causative in PD; however, it is possible that serological testing may not be optimal for detection of nocardial central nervous system infection.",,"['Hubble, J P', 'Cao, T', 'Kjelstrom, J A', 'Koller, W C', 'Beaman, B L']",,,,
,PMC,Thymus involution induced by mouse hepatitis virus A59 in BALB/c mice.,,PMC189556,,,"Mouse hepatitis virus A59 (MHV-A59) infection of adult BALB/c mice induced a severe, transient atrophy of the thymus. The effect was maximal at 1 week after infection, and thymuses returned to normal size by 2 weeks after infection. There was no effect of glucocorticoids, since thymus atrophy was also found in adrenalectomized, infected mice. In infected thymus, immature CD4+ CD8+ lymphocytes were selectively depleted, and apoptosis of lymphocytes was increased. The MHV receptor glycoprotein MHVR was detected on thymus epithelial cells but not on T lymphocytes. In a small number of stromal epithelial cells, but in very few lymphocytes, the viral genome was detectable by in situ hybridization. These observations suggested that MHV-A59-induced thymic atrophy results not from a generalized lytic infection of T lymphocytes but rather from apoptosis of immature double-positive T cells that might be caused by infection of a small proportion of thymus epithelial cells or from inappropriate secretion of some factor, such as a cytokine.",,"['Godfraind, C', 'Holmes, K V', 'Coutelier, J P']",,,,
,PMC,Investigation of the control of coronavirus subgenomic mRNA transcription by using T7-generated negative-sense RNA transcripts.,,PMC189519,,,"The subgenomic mRNAs of the coronavirus transmissible gastroenteritis virus (TGEV) are not produced in equimolar amounts. We have developed a reporter gene system to investigate the control of this differential subgenomic mRNA synthesis. Transcription of mRNAs by the TGEV polymerase was obtained from negative-sense RNA templates generated in situ from DNA containing a T7 promoter. A series of gene cassettes was produced; these cassettes comprised the reporter chloramphenicol acetyltransferase (CAT) gene downstream of transcription-associated sequences (TASs) (also referred to as intergenic sequences and promoters) believed to be involved in the synthesis of TGEV subgenomic mRNAs 6 and 7. The gene cassettes were designed so that negative-sense RNA copies of the CAT gene with sequences complementary to the TGEV TASs, or modified versions, at the 3' end would be synthesized in situ by T7 RNA polymerase. Using this system, we have demonstrated that CAT was expressed from mRNAs derived from the T7-generated negative-sense RNA transcripts only in TGEV-infected cells and only from transcripts possessing a TGEV negative-sense TAS. Analysis of the CAT mRNAs showed the presence of the TGEV leader RNA sequence at the 5' end, in keeping with observations that all coronavirus mRNAs have a 5' leader sequence corresponding to the 5' end of the genomic RNA. Our results indicated that the CAT mRNAs were transcribed from the in situ-synthesized negative-sense RNA templates without the requirement of TGEV genomic 5' or 3' sequences on the T7-generated negative-sense transcripts (3'-TAS-CAT-5'). Modification of the TGEV TASs indicated (i) that the degree of potential base pairing between the 3' end of the leader RNA and the TGEV negative-sense TAS was not the sole determinant of the amount of subgenomic mRNA transcribed and (ii) that other factors, including nucleotides flanking the TAS, are involved in the regulation of transcription of TGEV subgenomic mRNAs.",,"['Hiscox, J A', 'Mawditt, K L', 'Cavanagh, D', 'Britton, P']",,,,
,PMC,Mutational analysis of the leucine zipper motif in the Newcastle disease virus fusion protein.,,PMC189495,,,"The paramyxovirus fusion proteins have a highly conserved leucine zipper motif immediately upstream from the transmembrane domain of the F1 subunit (R. Buckland and F. Wild, Nature [London] 338:547, 1989). To determine the role of the conserved leucines in the oligomeric structure and biological activity of the Newcastle disease virus (NDV) fusion protein, the heptadic leucines at amino acids 481, 488, and 495 were changed individually and in combination to an alanine residue. While single amino acid changes had little effect on fusion, substitution of two or three leucine residues abolished the fusogenic activity of the protein, although cell surface expression of the mutants was higher than that of the wild-type protein. Substitution of all three leucine residues with alanine did not alter the size of the fusion protein oligomer as determined by sedimentation in sucrose gradients. Furthermore, deletion of the C-terminal 91 amino acids, including the leucine zipper motif and transmembrane domain, resulted in secretion of an oligomeric polypeptide. These results indicate that the conserved leucines are not necessary for oligomer formation but are required for the fusogenic ability of the protein. When the polar face of the potential alpha helix was altered by nonconservative changes of serine to alanine (position 473), glutamic acid to lysine or alanine (position 482), asparagine to lysine (position 485), or aspartic acid to alanine (position 489), the fusogenic ability of the protein was not significantly disrupted. In addition, a double mutant (E482A,D489A) which removed negative charges along one side of the helix had negligible effects on fusion activity.",,"['Reitter, J N', 'Sergel, T', 'Morrison, T G']",,,,
,PMC,The organization of the endoplasmic reticulum and the intermediate compartment in cultured rat hippocampal neurons.,,PMC301290,,,"The boundaries of the organelles of the biosynthetic endomembrane system are still controversial. In this paper we take advantage of the unique architectural organization of neurons to investigate the localization of a spectrum of compartment-specific markers with the goal of defining the location of the rough endoplasmic reticulum (ER), smooth ER, intermediate compartment, and the Golgi complex. Markers of the rough ER (signal sequence receptor), Golgi complex (mannosidase II), and the trans Golgi network (TGN38) were essentially restricted to the cell body and the initial segment of one of the cell's dendrites. In contrast the cytochemical reaction product for glucose 6 phosphate, a classical ER marker, in addition to staining ER structures in the cell body also reacted with smooth ER elements that extended into both axons and dendrites. These peripheral smooth ER elements also reacted at the immunofluorescence level for ER marker 3-hydroxy-3-methylglutaryl-coenzyme A reductase, as well as for calnexin and protein disulfide isomerase. We also analyzed the location of rab1, rab2, p58, the KDEL receptor, and beta-subunit of coatomer. These intermediate compartment markers were found predominantly in the cell body but also extended to the proximal parts of the dendrites. Collectively, our data argue that the ER of hippocampal neurons consists of functionally and spatially distinct and separated domains, and they stress the power of the hippocampal neuron system for investigations of the organization of the ER by light microscopy.",,"['Krijnse-Locker, J', 'Parton, R G', 'Fuller, S D', 'Griffiths, G', 'Dotti, C G']",,,,
,PMC,5 S Rrna Is Involved in Fidelity of Translational Reading Frame,,PMC1206744,,,"Chromosomal mutants (maintenance of frame = mof) in which the efficiency of -1 ribosomal frame-shifting is increased can be isolated using constructs in which lacZ expression is dependent upon a -1 shift of reading frame. We isolate a new mof mutation, mof9, in Saccharomyces cerevisiae and show that it is complemented by both single and multi-copy 5 S rDNA clones. Two independent insertion mutations in the rDNA locus (rDNA::LEU2 and rDNA::URA3) also display the Mof(-) phenotype and are also complemented by single and multi-copy 5 S rDNA clones. Mutant 5 S rRNAs expressed from a plasmid as 20-50% of total 5 S rRNA in a wild-type host also induced the Mof(-) phenotype. The increase in frameshifting is greatest when the lacZ reporter gene is expressed on a high copy, episomal vector. No differences were found in 5 S rRNA copy number or electrophoretic mobilities in mof9 strains. Both mof9 and rDNA::LEU2 increase the efficiency of +1 frameshifting as well but have no effect on readthrough of UAG or UAA termination codons, indicating that not all translational specificity is affected. These data suggest a role for 5 S rRNA in the maintenance of frame in translation.",,"['Dinman, J. D.', 'Wickner, R. B.']",,,,
,PMC,Induction of mucosal immunity in cotton rats to haemagglutinin-esterase glycoprotein of bovine coronavirus by recombinant adenovirus.,,PMC1383821,,,"An effective vaccine against enteric bovine coronavirus (BCV) must be able to induce mucosal immunity. We recently described the construction of recombinant human adenovirus type 5 (hAd5) carrying the BCV haemagglutinin-esterase (HE) gene in the early transcription region 3 of the adenovirus genome. In this study, we examined the induction of systemic and mucosal immune responses to the hAd5 vector carrying the BCV HE gene (AdBcHE) following intranasal or enteric immunization of cotton rats. Regardless of the route of administration, mucosal immunization with AdBcHE induced significant levels of anti-HE IgG antibodies in serum. In addition, following intranasal immunization with AdBcHE, significant levels of anti-HE IgA antibodies were found in lung washes of immunized cotton rats. Furthermore, the specific anti-HE antibodies in sera and mucosal secretions efficiently neutralized BCV infectivity in vitro. T-cell proliferation and cell-mediated cytotoxic responses against the BCV HE were elicited in the spleen of intranasally immunized animals. The results demonstrate that mucosal immunization with AdBcHE is capable of inducing both systemic and mucosal immunity to the BCV HE. These immune responses may be important in protecting animals from BCV infection.",,"['Baca-Estrada, M E', 'Liang, X', 'Babiuk, L A', 'Yoo, D']",,,,
,PMC,Tumor necrosis factor expression during mouse hepatitis virus-induced demyelinating encephalomyelitis.,,PMC189470,,,"Neutralizing anti-tumor necrosis factor alpha (TNF-alpha) antibody treatment of mice infected with the neurotropic JHMV strain of mouse hepatitis virus showed no reduction of either virus-induced encephalomyelitis or central nervous system demyelination. TNF-alpha-positive cells were present in the central nervous system during infection; however, TNF-alpha could not be colocalized with JHMV-infected cells. In vitro, TNF-alpha mRNA rapidly accumulated following JHMV infection; however, no TNF-alpha was secreted because of inhibition of translation. Both live and UV-inactivated virus inhibited TNF-alpha secretion induced by lipopolysaccharide. These data show that TNF-alpha is not secreted from infected cells and indicate that if contributes to either JHMV-induced acute encephalomyelitis nor primary demyelination.",,"['Stohlman, S A', 'Hinton, D R', 'Cua, D', 'Dimacali, E', 'Sensintaffar, J', 'Hofman, F M', 'Tahara, S M', 'Yao, Q']",,,,
,PMC,Induction of macrophage procoagulant activity by murine hepatitis virus strain 3: role of tyrosine phosphorylation.,,PMC189451,,,The induction of a unique macrophage procoagulant molecule by murine hepatitis virus strain 3 correlates with the severity of viral hepatitis. The role of tyrosine phosphorylation in the signalling pathway leading to procoagulant expression was studied. Murine hepatitis virus strain 3 initiated a rapid increase in phosphotyrosine accumulation. Tyrosine kinase inhibition precluded this increase and abrogated expression of the virus-induced procoagulant mouse fibrinogen-like protein (musfiblp) gene. These findings suggest that manipulation of this signalling pathway in vivo might represent a novel approach to treating this disease.,,"['Dackiw, A P', 'Zakrzewski, K', 'Nathens, A B', 'Cheung, P Y', 'Fingerote, R', 'Levy, G A', 'Rotstein, O D']",,,,
,PMC,The alpha-glucosidase inhibitor N-butyldeoxynojirimycin inhibits human immunodeficiency virus entry at the level of post-CD4 binding.,,PMC189444,,,"The alpha-glucosidase inhibitor N-butyldeoxynojirimycin (NB-DNJ) is a potent inhibitor of human immunodeficiency virus (HIV) replication and syncytium formation in vitro. However, the exact mechanism of action of NB-DNJ remains to be determined. In this study we have examined the impairment of HIV infectivity mediated by NB-DNJ. By two independent HIV entry assays [PCR-based HIV entry assay and entry of Cocal(HIV) pseudotypes], the reduction in infectivity was found to be due to an impairment of viral entry. No effect of NB-DNJ treatment was seen on the kinetics of the interaction between gp120 and CD4 (surface plasmon resonance; BIAcore) or on the binding of virus particles to H9 cells (using radiolabeled virions). We therefore conclude that a major mechanism of action of NB-DNJ as an inhibitor of HIV replication is the impairment of viral entry at the level of post-CD4 binding, due to an effect on viral envelope components.",,"['Fischer, P B', 'Collin, M', 'Karlsson, G B', 'James, W', 'Butters, T D', 'Davis, S J', 'Gordon, S', 'Dwek, R A', 'Platt, F M']",,,,
,PMC,The neurovirulent GDVII strain of Theiler's virus can replicate in glial cells.,,PMC189416,,,"The distribution, spread, neuropathology, tropism, and persistence of the neurovirulent GDVII strain of Theiler's virus in the central nervous system (CNS) was investigated in mice susceptible and resistant to chronic demyelinating infection with TO strains. Following intracerebral inoculation, the virus spread rapidly to specific areas of the CNS. There were, however, specific structures in which infection was consistently undetectable. Virus spread both between adjacent cell bodies and along neuronal pathways. The distribution of the infection was dependent on the site of inoculation. The majority of viral RNA-positive cells were neurons. Many astrocytes were also positive. Infection of both of these cell types was lytic. In contrast, viral RNA-positive oligodendrocytes were rare and were observed only in well-established areas of infection. The majority of oligodendrocytes in these areas were viral RNA negative and were often the major cell type remaining; however, occasional destruction of these cells was observed. No differences in any of the above parameters were observed between CBA and BALB/c mice, susceptible and resistant, respectively, to chronic CNS demyelinating infection with TO strains of Theiler's virus. By using Southern blot hybridization to detect reverse-transcribed PCR-amplified viral RNA sequences, no virus persistence could be detected in the CNS of immunized mice surviving infection with GDVII. In conclusion, the GDVII strain of Theiler's murine encephalomyelitis virus cannot persist in the CNS, but this is not consequent upon an inability to infect glial cells, including oligodendrocytes.",,"['Simas, J P', 'Dyson, H', 'Fazakerley, J K']",,,,
,PMC,Rotavirus-induced fusion from without in tissue culture cells.,,PMC189413,,,"We present the first evidence of fusion from without induced in tissue culture cells by a nonenveloped virus. Electron micrographs of two strains of rotavirus, bovine rotavirus C486 and rhesus rotavirus, show that virally mediated cell-cell fusion occurs within 1 h postinfection. Trypsin activation is necessary for rotavirus to mediate cell-cell fusion. The extent of fusion is relative to the amount of virus used, and maximum fusion occurs between pHs 6.5 and 7.5. Fusion does not require virus-induced protein synthesis, as virus from both an empty capsid preparation and from an EDTA-treated preparation, which is noninfectious, can induce fusion. Incubation of rotavirus with neutralizing and nonneutralizing monoclonal antibodies before addition to cells indicates that viral protein 4 (VP4; in the form of VP5* and VP8*) and VP7 are involved in fusion. Light and electron micrographs document this fusion, including the formation of pores or channels between adjacent fused cells. These data support direct membrane penetration as a possible route of infection. Moreover, the assay should be useful in determining the mechanisms of cell entry by rotavirus.",,"['Falconer, M M', 'Gilbert, J M', 'Roper, A M', 'Greenberg, H B', 'Gavora, J S']",,,,
,PMC,Persistent infection of cultured cells with mouse hepatitis virus (MHV) results from the epigenetic expression of the MHV receptor.,,PMC189405,,,"The A59 strain of murine coronavirus mouse hepatitis virus (MHV) can cause persistent infection of 17C1-1 cells and other murine cell lines. Persistently infected cultures released large amounts of virus (10(7) to 10(8) PFU/ml) and were resistant to superinfection with MHV but not to infection with unrelated Semliki Forest and vesicular stomatitis viruses. The culture medium from persistently infected cultures did not contain a soluble inhibitor such as interferon that protected uninfected cells from infection by MHV or vesicular stomatitis virus. The persistent infection was cured if fewer than 100 cells were transferred during subculturing, and such cured cultures were susceptible to reinfection and the reestablishment of persistent infection. Cultures of 17C1-1 cells that had been newly cloned from single cells consisted of a mixture of MHV-resistant and -susceptible cells. 17C1-1/#97 cells, which were cured by subcloning after 97 passages of a persistently infected culture over a 1-year period, contained 5 to 10% of their population as susceptible cells, while 17C1-1/#402 cells, which were cured by subcloning after 402 passages over a 3-year period, had less than 1% susceptible cells. Susceptibility to infection correlated with the expression of MHV receptor glycoprotein (MHVR [Bgp1a]). Fluorescence-activated cell sorter analysis with antibody to MHVR showed that 17C1-1/#97 cells contained a small fraction of MHVR-expressing cells. These MHVR-expressing cells were selectively eliminated within 24 h after challenge with MHV-A59, and pretreatment of 17C1-1/#97 cells with monoclonal antibody CC1, which binds to the N-terminal domain of MHVR, blocked infection. We conclude that the subpopulation of MHVR-expressing cells were infected and killed in acutely or persistently infected cultures, while the subpopulation of MHVR-nonexpressing cells survived and proliferated. The subpopulation of MHVR-negative cells produced a small proportion of progeny cells that expressed MHVR and became infected, thereby maintaining the persistent infection as a steady-state carrier culture. Thus, in 17C1-1 cell cultures, the unstable or epigenetic expression of MHVR permitted the establishment of a persistent, chronic infection.",,"['Sawicki, S G', 'Lu, J H', 'Holmes, K V']",,,,
,PMC,Construction of murine coronavirus mutants containing interspecies chimeric nucleocapsid proteins.,,PMC189397,,,"Targeted RNA recombination was used to construct mouse hepatitis virus (MHV) mutants containing chimeric nucleocapsid (N) protein genes in which segments of the bovine coronavirus N gene were substituted in place of their corresponding MHV sequences. This defined portions of the two N proteins that, despite evolutionary divergence, have remained functionally equivalent. These regions included most of the centrally located RNA-binding domain and two putative spacers that link the three domains of the N protein. By contrast, the amino terminus of N, the acidic carboxy-terminal domain, and a serine- and arginine-rich segment of the central domain could not be transferred from bovine coronavirus to MHV, presumably because these parts of the molecule participate in protein-protein interactions that are specific for each virus (or, possibly, each host). Our results demonstrate that targeted recombination can be used to make extensive substitutions in the coronavirus genome and can generate recombinants that could not otherwise be made between two viruses separated by a species barrier. The implications of these findings for N protein structure and function as well as for coronavirus RNA recombination are discussed.",,"['Peng, D', 'Koetzner, C A', 'McMahon, T', 'Zhu, Y', 'Masters, P S']",,,,
,PMC,Membrane protein molecules of transmissible gastroenteritis coronavirus also expose the carboxy-terminal region on the external surface of the virion.,,PMC189361,,,"The binding domains of four monoclonal antibodies (MAbs) specific for the M protein of the PUR46-MAD strain of transmissible gastroenteritis coronavirus (TGEV) have been located in the 46 carboxy-terminal amino acids of the protein by studying the binding of MAbs to recombinant M protein fragments. Immunoelectron microscopy using these MAbs demonstrated that in a significant proportion of the M protein molecules, the carboxy terminus is exposed on the external surface both in purified viruses and in nascent TGEV virions that recently exited infected swine testis cells. The same MAbs specifically neutralized the infectivity of the PUR46-MAD strain, indicating that the C-terminal domain of M protein is exposed on infectious viruses. This topology of TGEV M protein probably coexists with the structure currently described for the M protein of coronaviruses, which consists of an exposed amino terminus and an intravirion carboxy-terminal domain. The presence of a detectable number of M protein molecules with their carboxy termini exposed on the surface of the virion has relevance for viral function, since it has been shown that the carboxy terminus of M protein is immunodominant and that antibodies specific for this domain both neutralize TGEV and mediate the complement-dependent lysis of TGEV-infected cells.",,"['Risco, C', 'Antón, I M', 'Suñé, C', 'Pedregosa, A M', 'Martín-Alonso, J M', 'Parra, F', 'Carrascosa, J L', 'Enjuanes, L']",,,,
,PMC,Pattern of disease after murine hepatitis virus strain 3 infection correlates with macrophage activation and not viral replication.,,PMC189358,,,"Murine hepatitis virus strain (MHV-3) produces a strain-dependent pattern of disease which has been used as a model for fulminant viral hepatitis. This study was undertaken to examine whether there was a correlation between macrophage activation and susceptibility or resistance to MHV-3 infection. Peritoneal macrophages were isolated from resistant A/J and susceptible BALB/cJ mice and, following stimulation with MHV-3 or lipopolysaccharide (LPS), analyzed for transcription of mRNA and production of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), mouse fibrinogen-like protein (musfiblp), tissue factor (TF), leukotriene B4, and prostaglandin E2 (PGE2). Macrophages from BALB/cJ mice produced greater amounts of IL-1, TNF-alpha, TGF-beta, leukotriene B4, and musfiblp following MHV-3 infection than macrophages from resistant A/J mice, whereas in response to LPS, equivalent amounts of IL-1, TNF-alpha, TGF-beta, and TF were produced by macrophages from both strains of mice. Levels of mRNA of IL-1, TNF-alpha, and musfiblp were greater and more persistent in BALB/cJ than in A/J macrophages, whereas the levels and kinetics of IL-1, TNF-alpha, and TF mRNA following LPS stimulation were identical in macrophages from both strains of mice. Levels of production of PGE2 by MHV-3-stimulated macrophages from resistant and susceptible mice were equivalent; however, the time course for induction of PGE2, differed, but the total quantity of PGE2 produced was insufficient to inhibit induction of musfiblp, a procoagulant known to correlate with development of fulminant hepatic necrosis in susceptible mice. These results demonstrate marked differences in production of inflammatory mediators to MHV-3 infection in macrophages from resistant A/J and susceptible BALB/cJ mice, which may explain the marked hepatic necrosis and fibrin deposition and account for the lethality of MHV-3 in susceptible mice.",,"['Pope, M', 'Rotstein, O', 'Cole, E', 'Sinclair, S', 'Parr, R', 'Cruz, B', 'Fingerote, R', 'Chung, S', 'Gorczynski, R', 'Fung, L']",,,,
,PMC,The N-terminal hydrophobic region of the mature phosphate translocator is sufficient for targeting to the chloroplast inner envelope membrane.,http://dx.doi.org/10.1105/tpc.7.9.1421,PMC160965,,,"To locate the sequence required for directing the phosphate translocator to the chloroplast inner envelope membrane, a series of chimeric proteins constituting parts of the phosphate translocator and the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase, which is normally located in the stroma, has been produced. Reciprocal exchanges of the presequences and mature sequences of the phosphate translocator and the small subunit indicated that the phosphate translocator presequence contains stromal targeting information and that the mature protein is responsible for inner envelope membrane targeting. Chimeric proteins containing the N-terminal 46 amino acid residues of the phosphate translocator were directed to the inner envelope membrane. Subdivision of this region into its composite hydrophilic and hydrophobic regions showed that the hydrophobic region alone, which consists of amino acid residues 24 to 45, was able to direct the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase to the inner envelope membrane.",,"['Knight, J S', 'Gray, J C']",,,,
,PMC,Canine Lyme borreliosis in Ontario--a case report.,,PMC1687013,,,,,"Wiebe, K R",,,,
,PMC,Differential activation of mouse hepatitis virus-specific CD4+ cytotoxic T cells is defined by peptide length.,,PMC1383777,,,"In this study we have characterized the core epitope recognized by the MHV-A59-specific CD4+ cytotoxic T lymphocyte (CTL) clones HS1 and B6.1, derived from BALB/c and C57/BL6 mice, respectively. These CD4+ clones respond to the promiscuous peptide fragment S-329-343 of the glycoprotein S of MHV-A59. The results indicate that the core peptides of both clones overlap but are not identical. The core region of the HS1 clone is an 8-mer, and comprises the amino acid residues S-332-339, whereas the minimal epitope for clone B6.1 is a 9-mer and comprises the amino acid residues S-334-342. The peptide fragment S-329-343 activates all T-cell effector functions, including proliferation, cytokine secretion and cytolysis. However, in the present study we show that T-cell activation is not an all-or-none phenomenon, in which T-cell stimulation leads to activation of all T-cell effector functions. It appears that changes in the length of a peptide ligand can differentially activate the cytolytic machinery from proliferation and cytokine secretion. Furthermore, the results indicate that, in our case, modulation of the flanking residues of the core epitopes did not convert the cytokine profile of polarized T-helper type-1 (Th1) clones into a Th2-type pattern.",,"['Heemskerk, M H', 'Schoemaker, H M', 'De Jong, I', 'Schijns, V E', 'Spaan, W J', 'Boog, C J']",,,,
,PMC,Immunomodulation in the treatment of multiple sclerosis and amyotrophic lateral sclerosis: a model for autoimmune disorders.,,PMC2607874,,,"Seventeen multiple sclerosis (MS) patients progressing under conventional therapy (average treatment duration: 3 years) with performance status 3-4 (mean Disability Status Scale [DSS]: 82) who demonstrated circulating lymphokine inhibitor factors were selected for a monthly immunomodulatory protocol using plasmapheresis, followed by 3 days of human intravenous immunoglobulin, and low-dose methylprednisolone, cyclophosphamide, interferon-a, and interferon-g, as well as octreide. Twelve of the 17 patients presented with visual problems, 12 had lower extremity weakness or paraperesis/paralysis, and 6 had bladder/bowel dysfunction. Following 4 months of therapy, 4 recovered completely, 7 showed loss of paralysis/paraparesis, and 5 had improvement in lower extremity weakness. One patient progressed (mean DSS: 51). Lymphokine inhibitor factors declined in 14 patients with concomitant normalization of circulating immune complexes. Eight patients experienced rises in CD4 levels with stabilization of CD8 levels. Hypotension and hypocalcemia were observed during plasmapheresis. Twelve patients with amyotrophic lateral sclerosis with poor performance status also were studied. Four of the 12 improved with the regimen, whereas six stabilized disease. Similar alterations in laboratory parameters were described. The rationale for this approach is discussed.",,"['Alonso, K.', 'Medenica, R.']",,,,
,PMC,Infectious subvirion particles of reovirus type 3 Dearing exhibit a loss in infectivity and contain a cleaved sigma 1 protein.,,PMC189323,,,"Mammalian reoviruses exhibit differences in the capacity to grow in intestinal tissue: reovirus type 1 Lang (T1L), but not type 3 Dearing (T3D), can be recovered in high titer from intestinal tissue of newborn mice after oral inoculation. We investigated whether in vitro protease treatment of virions of T1L and T3D, using conditions to generate infectious subvirion particles (ISVPs) as occurs in the intestinal lumen of mice (D. K. Bodkin, M. L. Nibert, and B. N. Fields, J. Virol. 63:4676-4681, 1989), affects viral infectivity. Chymotrypsin treatment of T1L was associated with a 2-fold increase in viral infectivity, whereas identical treatment of T3D resulted in a 10-fold decrease in infectivity. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we found that loss of T3D infectivity was correlated with cleavage of its sigma 1 protein. We used reassortant viruses to identify viral determinants of infectivity loss and sigma 1 cleavage and found that both phenotypes segregate with the sigma 1-encoding S1 gene. Comparable results were obtained when trypsin treatment of virions of T1L and T3D was used. In experiments to determine the fate of sigma 1 fragments following cleavage, the capacity of anti-sigma 1 monoclonal antibody G5 to neutralize infectivity of T3D ISVPs was significantly decreased in comparison with its capacity to neutralize infectivity of virions, suggesting that a sigma 1 domain bound by G5 is lost from viral particles after proteolytic digestion. In contrast to the decrease in infectivity, chymotrypsin treatment of T3D virions leading to generation of ISVPs resulted in a 10-fold increase in their capacity to produce hemagglutination, indicating that a domain of sigma 1 important for binding to sialic acid remains associated with viral particles after sigma 1 cleavage. Neuraminidase treatment of L cells substantially decreased the yield of T3D ISVPs in comparison with the yield of virions, indicating that a sigma 1 domain important for binding sialic acid also can mediate attachment of T3D ISVPs to L cells and lead to productive infection. These results suggest that cleavage of T3D sigma 1 protein following oral inoculation of newborn mice is at least partly responsible for the decreased growth of T3D in the intestine and provide additional evidence that T3D sigma 1 contains more than a single receptor-binding domain.",,"['Nibert, M L', 'Chappell, J D', 'Dermody, T S']",,,,
,PMC,Association of mouse fibrinogen-like protein with murine hepatitis virus-induced prothrombinase activity.,,PMC189320,,,"Previously, we demonstrated induction of a unique macrophage prothrombinase during infection of BALB/cJ mice by mouse hepatitis virus strain 3 (MHV-3). By immunologic screening, a clone representing this prothrombinase was isolated from a cDNA library and sequenced. The sequence identified this clone as representing part of a gene, musfiblp, that encodes a fibrinogen-like protein. Six additional clones were isolated, and one clone, p11-3-1, encompassed the entire coding region of musfiblp. Murine macrophages did not constitutively express musfiblp but, when infected with MHV-3, synthesized musfiblp-specific mRNA. musfiblp mRNA induction was earlier and significantly greater in BALB/cJ than A/J macrophages. Prothrombinase activity was demonstrated when musfiblp was expressed from p11-3-1 in RAW 264.7 cells. These data suggest that musfiblp encodes the MHV-induced prothrombinase.",,"['Parr, R L', 'Fung, L', 'Reneker, J', 'Myers-Mason, N', 'Leibowitz, J L', 'Levy, G']",,,,
,PMC,Characterization of a murine coronavirus defective interfering RNA internal cis-acting replication signal.,,PMC189312,,,"The mouse hepatitis virus (MHV) sequences required for replication of the JHM strain of MHV defective interfering (DI) RNA consist of three discontinuous genomic regions: about 0.47 kb from both terminal sequences and a 0.13-kb internal region present at about 0.9 kb from the 5' end of the DI genome. In this study, we investigated the role of the internal 0.13-kb region in MHV RNA replication. Overall sequences of the 0.13-kb regions from various MHV strains were similar to each other, with nucleotide substitutions in some strains; MHV-A59 was exceptional, with three nucleotide deletions. Computer-based secondary-structure analysis of the 0.13-kb region in the positive strand revealed that most of the MHV strains formed the same or a similar main stem-loop structure, whereas only MHV-A59 formed a smaller main stem-loop structure. The RNA secondary structures in the negative strands were much less uniform among the MHV strains. A series of DI RNAs that contained MHV-JHM-derived 5'- and 3'-terminal sequences plus internal 0.13-kb regions derived from various MHV strains were constructed. Most of these DI RNAs replicated in MHV-infected cells, except that MRP-A59, with a 0.13-kb region derived from MHV-A59, failed to replicate. Interestingly, replication of MRP-A59 was temperature dependent; it occurred at 39.5 degrees C but not at 37 or 35 degrees C, whereas a DI RNA with an MHV-JHM-derived 0.13-kb region replicated at all three temperatures. At 37 degrees C, synthesis of MRP-A59 negative-strand RNA was detected in MHV-infected and MRP-A59 RNA-transfected cells. Another DI RNA with the internal 0.13-kb region deleted also synthesized negative-strand RNA in MHV-infected cells. MRP-A59-transfected cells were shifted from 39.5 to 37 degrees C at 5.5 h postinfection, a time when most MHV negative-strand RNAs have already accumulated; after the shift, MRP-A59 positive-strand RNA synthesis ceased. The minimum sequence required for maintenance of the positive-strand major stem-loop structure and biological function of the MHV-JHM 0.13-kb region was about 57 nucleotides. Function was lost in the 50-nucleotide sequence that formed a positive-strand stem-loop structure identical to that of MHV-A59. These studies suggested that the RNA structure made by the internal sequence was important for positive-strand MHV RNA synthesis.",,"['Kim, Y N', 'Makino, S']",,,,
,PMC,Picornavirus-specific CD4+ T lymphocytes possessing cytolytic activity confer protection in the absence of prophylactic antibodies.,,PMC189306,,,"Picornaviruses are a family of positive-strand RNA viruses that are responsible for a variety of devastating human and animal diseases. An attenuated strain of mengovirus (vMC24) is serologically indistinguishable from the lethal murine wild-type mengovirus and encephalomyocarditis virus (EMCV). Immunogen-specific stimulation of vMC24-immune splenocytes in vitro demonstrates preferential activation of CD4+ lymphocytes. vMC24-immune splenocytes adoptively transferred to naive recipients conferred protection against lethal EMCV challenge. Immune splenocytes, expanded in vitro, were > 92% CD4+ T lymphocytes. Interestingly, adoptive transfer of these expanded cells engendered protection against lethal challenge. In vivo depletion of CD4+ T lymphocytes prior to lethal challenge abrogated survival of transfer recipients, confirming that CD4+ T lymphocytes were essential for protection. Subsequent rechallenge of vMC24-immune splenocyte recipients with a greater EMCV dose elicited serum neutralizing antibody titers paralleling the high titers observed in vMC24-immunized mice. Unexpectedly, an augmented humoral response was absent in vMC24-specific CD4+ T-cell recipients after the secondary challenge. Moreover, comparably low serum neutralizing antibody titers failed to protect passive transfer recipients when correspondingly challenged. vMC24-immune splenocytes expanded in vitro (> 94% CD4+) lysed vMC24-infected A20.J target cells. The ability to transfer protection with primed CD4+ T cells, in the absence of primed B lymphocytes or immune sera, is novel for picornaviral infections. Consequently, mechanisms such as CD4+ cytolytic T-lymphocyte activity are implicated in mediating protection.",,"['Neal, Z C', 'Splitter, G A']",,,,
,PMC,The two major envelope proteins of equine arteritis virus associate into disulfide-linked heterodimers.,,PMC189270,,,"In a coimmunoprecipitation assay with monospecific antisera, the two major envelope proteins GL and M of equine arteritis virus were found to occur in heteromeric complexes in virions and infected cells. While the GL protein associated with M rapidly and efficiently, newly synthesized M protein was incorporated into complexes at a slower rate, which implies that it interacts with GL molecules synthesized earlier. Analysis under nonreducing conditions revealed that the GL/M complexes consist of disulfide-linked heterodimeric structures. Pulse-chase experiments showed that virtually all GL monomers ended up in heterodimers, whereas a fraction of the M protein persisted as monomers. The M protein also formed covalently linked homodimers, but only the heterodimers were incorporated into virus particles.",,"['de Vries, A A', 'Post, S M', 'Raamsman, M J', 'Horzinek, M C', 'Rottier, P J']",,,,
,PMC,"Structural analysis of TRAS1, a novel family of telomeric repeat-associated retrotransposons in the silkworm, Bombyx mori.",,PMC230694,,,"We characterized TRAS1, a retrotransposable element which was inserted into the telomeric repetitive sequence (CCTAA)n of the silkworm, Bombyx mori. The complete sequence of TRAS1, a stretch of 7.8 kb with a poly(A) tract at the 3' end, was determined. No long terminal repeat (LTR) was found at the termini of the element. TRAS1 contains gag- and pol-like open reading frames (ORFs) which are similar to those of non-LTR retrotransposons. The two ORFs overlap but are one nucleotide out of frame (+1 frameshift). Most of the approximately 250 copies of TRAS1 elements in the genome were highly conserved in the structure. Chromosomal in situ hybridization showed that TRAS1 elements are clustered at the telomeres of Bombyx chromosomes. A phylogenetic analysis using the amino acid sequence of the reverse transcriptase domain within the pol-like ORF revealed that TRAS1 falls into one lineage with R1, which is a family of non-LTR retrotransposons inserted into the same site within the 28S ribosomal DNA unit in most insects. TRAS1 may have been derived from R1 and changed the target specificity so that TRAS1 inserts into the telomeric repetitive sequence (CCTAA)n. Southern hybridization and Bal 31 exonuclease analyses showed that TRAS1 elements are clustered proximal to the terminal long tract of (CCTAA)n. TRAS1 is a novel family of non-LTR retrotransposons which are inserted into the telomeric repetitive sequences as target sites.",,"['Okazaki, S', 'Ishikawa, H', 'Fujiwara, H']",,,,
,PMC,Unconventional Agents and Unclassified Viruses: Recent Advances in Biology and Epidemiology,,PMC1686979,,,,,"Jordan, Lorne",,,,
,PMC,Dynamics of the intracerebral and splenic cytokine mRNA production in Toxoplasma gondii-resistant and -susceptible congenic strains of mice.,,PMC1383914,,,"Oral infection with a low-virulence strain of Toxoplasma gondii (Tg) induced a persisting encephalitis in resistant strains of mice. In the present study we have examined transcripts of various cytokines during acute and chronic stages of murine Tg encephalitis. In the brain of infected animals, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-6, IL-10 and IL-12 mRNA were induced to a significant extent, but only low levels of IL-4 mRNA were detectable. A similar cytokine profile was observed in the spleen. However, in contrast to the brain, the increase of IL-2 mRNA was particularly pronounced in the spleen, whereas the opposite was found for IFN-gamma and TNF-alpha mRNA. Thus, cytokines involved in T-cell proliferation were more prevalent in the spleen, but in the brain, where Tg actively multiplies, the effector molecules IFN-gamma and TNF-alpha were preferentially up-regulated. In addition, a detailed analysis of cytokine mRNA levels in major histocompatibility complex (MHC)-congenic strains of BALB and B10 mice revealed that the genetically regulated susceptibility to Tg was correlated with the amount of intracerebrally produced cytokine mRNA for IFN-gamma, TNF-alpha and IL-6. Mice with a strong increase of these cytokine mRNA were significantly better protected against Tg. This indicates that the outcome of toxoplasmosis may be critically dependent on an adequately regulated intracerebral immune response.",,"['Deckert-Schlüter, M', 'Albrecht, S', 'Hof, H', 'Wiestler, O D', 'Schlüter, D']",,,,
,PMC,Detection of porcine reproductive and respiratory syndrome virus in boar semen by PCR.,,PMC228258,,,"Porcine reproductive and respiratory syndrome virus (PRRSV) causes a devastating disease in swine. The presence and transmission of PRRSV by boar semen has been demonstrated by using a swine bioassay. In this assay, 4- to 8-week-old pigs were inoculated intraperitoneally with semen from PRRSV-infected boars. Seroconversion of these piglets indicated the presence of PRRSV in semen. Seroconversion in gilts has also been demonstrated following artificial insemination with semen from PRRSV-infected boars. These methods of detecting PRRSV in boar semen are time-consuming, laborious, and expensive. The objective of this study was to develop a reliable and sensitive PCR assay to directly detect PRRSV in boar semen. Primers from open reading frames 1b and 7 of the PRRSV genome were used in nested PCRs. Virus was detected at concentrations as low as 10 infectious virions per ml in PRRSV-spiked semen. Specificity was confirmed by using a nested PCR and a 32P-labeled oligonucleotide probe. The primers did not react with related arteriviruses or other swine viruses. The PCR assay showed good correlation with the swine bioassay, and both methods were superior to virus isolation. To consistently identify PRRSV in boar semen, the cell fraction was separated by centrifugation at 600 x g for 20 min, a lysis buffer without a reducing agent (2-mercaptoethanol) was used, and nondiluted and 1:20-diluted cell fractions were evaluated by PCR. PRRSV was not reliably detected in the seminal plasma fraction of boar semen.",,"['Christopher-Hennings, J', 'Nelson, E A', 'Nelson, J K', 'Hines, R J', 'Swenson, S L', 'Hill, H T', 'Zimmerman, J J', 'Katz, J B', 'Yaeger, M J', 'Chase, C C']",,,,
,PMC,Processing and evolution of the N-terminal region of the arterivirus replicase ORF1a protein: identification of two papainlike cysteine proteases.,,PMC189193,,,"Two adjacent papainlike cysteine protease (PCP) domains, PCP alpha and PCP beta, were identified in the N-terminal region of the open reading frame 1a replicase proteins of the arteriviruses porcine reproductive and respiratory syndrome virus and lactate dehydrogenase-elevating virus. The replicase of the related virus equine arteritis virus contains only one active PCP in the corresponding region. Sequence comparison revealed that the equine arteritis virus PCP alpha counterpart probably was inactivated by loss of its catalytic Cys residue. For both porcine reproductive and respiratory syndrome virus and lactate dehydrogenase-elevating virus, the generation of two processing products, nsp1 alpha and nsp1 beta, was demonstrated by in vitro translation. Site-directed mutagenesis and sequence comparison were used to identify the putative active-site residues of the PCP alpha and PCP beta protease domains and to show that they mediate the nsp1 alpha/1 beta and nsp1 beta/2 cleavages, respectively.",,"['den Boon, J A', 'Faaberg, K S', 'Meulenberg, J J', 'Wassenaar, A L', 'Plagemann, P G', 'Gorbalenya, A E', 'Snijder, E J']",,,,
,PMC,Characterization of a human coronavirus (strain 229E) 3C-like proteinase activity.,,PMC189173,,,"The RNA polymerase gene of human coronavirus (HCV) 229E encodes a large polyprotein that contains domains with motifs characteristic of both papain-like cysteine proteinases and proteinases with homology to the 3C proteinase of picornaviruses. In this study, we have, first, expressed the putative HCV 229E 3C-like proteinase domain as part of a beta-galactosidase fusion protein in Escherichia coli and have shown that the expressed protein has proteolytic activity. The substitution of one amino acid within the predicted proteinase domain (His-3006-->Asp-3006) abolishes, or at least significantly reduces, this activity. Amino-terminal sequence analysis of a purified, 34-kDa cleavage product shows that the bacterial fusion protein is cleaved at the dipeptide Gln-2965-Ala-2966, which is the predicted amino-terminal end of the putative 3C-like proteinase domain. Second, we have confirmed the proteolytic activity of a bacterially expressed polypeptide with the amino acid sequence of the predicted HCV 229E 3C-like proteinase by trans cleavage of an in vitro translated polypeptide encoded within open reading frame 1b of the RNA polymerase gene. Finally, using fusion protein-specific antiserum, we have identified a 34-kDa, 3C-like proteinase polypeptide in HCV 229E-infected MRC-5 cells. This polypeptide can be detected as early as 3 to 5 h postinfection but is present in the infected cell in very low amounts. These data contribute to the characterization of the 3C-like proteinase activity of HCV 229E.",,"['Ziebuhr, J', 'Herold, J', 'Siddell, S G']",,,,
,PMC,Pseudotype virions formed between mouse hepatitis virus and lactate dehydrogenase-elevating virus (LDV) mediate LDV replication in cells resistant to infection by LDV virions.,,PMC189161,,,"Infection of cultures of peritoneal macrophages with both lactate dehydrogenase-elevating virus (LDV) and mouse hepatitis virus (MHV) resulted in the formation of pseudotype virions containing LDV RNA which productively infected cells that are resistant to infection by intact LDV virions but not to infection by MHV. These cells were mouse L-2 and 3T3-17Cl-1 cells as well as residual peritoneal macrophages from persistently LDV-infected mice. Productive LDV infection of these cells via pseudotype virions was inhibited by antibodies to the MHV spike protein or to the MHV receptor, indicating that LDV RNA entered the cells via particles containing the MHV envelope. Simultaneous exposure of L-2 cells to both LDV and MHV resulted in infection by MHV but not by LDV. The results indicate that an internal block to LDV replication is not the cause of the LDV nonpermissiveness of many cell types, including the majority of the macrophages in an adult mouse. Instead, LDV permissiveness is restricted to a subpopulation of mouse macrophages because only these cells possess a surface component that acts as an LDV receptor.",,"['Even, C', 'Plagemann, P G']",,,,
,PMC,"Sorting of yeast alpha 1,3 mannosyltransferase is mediated by a lumenal domain interaction, and a transmembrane domain signal that can confer clathrin-dependent Golgi localization to a secreted protein.",,PMC301242,,,"alpha 1,3 mannosyltransferase (Mnn1p) is a type II integral membrane protein that is localized to the yeast Golgi complex. We have examined the signals within Mnn1p that mediate Golgi localization by expression of fusion proteins comprised of Mnn1p and the secreted protein invertase. The N-terminal transmembrane domain (TMD) of Mnn1p is sufficient to localize invertase to the Golgi complex by a mechanism that is not saturable by approximately 15-20 fold overexpression. Furthermore, the TMD-mediated localization mechanism is clathrin dependent, as an invertase fusion protein bearing only the Mnn1p TMD is mislocalized to the plasma membrane of a clathrin heavy chain mutant. The Mnn1-invertase fusion proteins are not retained in the Golgi complex as efficiently as Mnn1p, suggesting that other signals may be present in the wild-type protein. Indeed, the Mnn1p lumenal domain (Mnn1-s) is also localized to the Golgi complex when expressed as a functional, soluble protein by exchanging its TMD for a cleavable signal sequence. In contrast to the Mnn1-invertase fusion proteins, overexpression of Mnn1-s saturates its retention mechanism, and results in the partial secretion of this protein. These data indicate that Mnn1p has separable Golgi localization signals within both its transmembrane and lumenal domains.",,"['Graham, T R', 'Krasnov, V A']",,,,
,PMC,An RNA pseudoknot is an essential structural element of the internal ribosome entry site located within the hepatitis C virus 5' noncoding region.,,PMC1482419,,,"Translation of the human hepatitis C virus (HCV) RNA genome occurs by a mechanism known as ""internal ribosome entry."" This unusual strategy of translation is employed by naturally uncapped picornaviral genomic RNAs and several cellular mRNAs. A common feature of these RNAs is a relatively long 5' noncoding region (NCR) that folds into a complex secondary structure harboring an internal ribosome entry site (IRES). Evidence derived from the use of dicistronic expression systems, combined with an extensive mutational analysis, demonstrated the presence of an IRES within the HCV 5'NCR. The results of our continued mutational analysis to map the critical structural elements of the HCV IRES has led to the identification of a pseudoknot structure upstream of the initiator AUG. The evidence presented in this study is based upon the mutational analysis of the putative pseudoknot structure. This is further substantiated by biochemical and enzymatic probing of the wild-type and mutant 5'NCR. Further, the thermodynamic calculations, based upon a modified RNAKNOT program, are consistent with the presence of a pseudoknot structure located upstream of the initiator AUG. Maintenance of this structural element is critical for internal initiation of translation. The pseudoknot structure in the 5'NCR represents a highly conserved feature of all HCV subtypes and members of the pestivirus family, including hog cholera virus and bovine viral diarrhea virus.",,"['Wang, C', 'Le, S Y', 'Ali, N', 'Siddiqui, A']",,,,
,PMC,Two independent targeting signals in the cytoplasmic domain determine trans-Golgi network localization and endosomal trafficking of the proprotein convertase furin.,,PMC398356,,,"Furin, a subtilisin-like eukaryotic endoprotease, is responsible for proteolytic cleavage of cellular and viral proteins transported via the constitutive secretory pathway. Cleavage occurs at the C-terminus of basic amino acid sequences, such as R-X-K/R-R and R-X-X-R. Furin was found predominantly in the trans-Golgi network (TGN), but also in clathrin-coated vesicles dispatched from the TGN, on the plasma membrane as an integral membrane protein and in the medium as an anchorless enzyme. When furin was vectorially expressed in normal rat kidney (NRK) cells it accumulated in the TGN similarly to the endogenous glycoprotein TGN38, often used as a TGN marker protein. The signals determining TGN targeting of furin were investigated by mutational analysis of the cytoplasmic tail of furin and by using the hemagglutinin (HA) of fowl plague virus, a protein with cell surface destination, as a reporter molecule, in which membrane anchor and cytoplasmic tail were replaced by the respective domains of furin. The membrane-spanning domain of furin grafted to HA does not localize the chimeric molecule to the TGN, whereas the cytoplasmic domain does. Results obtained on furin mutants with substitutions and deletions of amino acids in the cytoplasmic tail indicate that wild-type furin is concentrated in the TGN by a mechanism involving two independent targeting signals, which consist of the acidic peptide CPSDSEEDEG783 and the tetrapeptide YKGL765. The acidic signal in the cytoplasmic domain of a HA-furin chimera is necessary and sufficient to localize the reporter molecule to the TGN, whereas YKGL is a determinant for targeting to the endosomes. The data support the concept that the acidic signal, which is the dominant one, retains furin in the TGN, whereas the YKGL motif acts as a retrieval signal for furin that has escaped to the cell surface.",,"['Schäfer, W', 'Stroh, A', 'Berghöfer, S', 'Seiler, J', 'Vey, M', 'Kruse, M L', 'Kern, H F', 'Klenk, H D', 'Garten, W']",,,,
,PMC,Translation but not the encoded sequence is essential for the efficient propagation of the defective interfering RNAs of the coronavirus mouse hepatitis virus.,,PMC189091,,,"The defective interfering (DI) RNA MIDI of mouse hepatitis virus strain A59 (MHV-A59) contains a large open reading frame (ORF) spanning almost its entire genome. This ORF consists of sequences derived from ORF1a, ORF1b, and the nucleocapsid gene. We have previously demonstrated that mutations that disrupt the ORF decrease the fitness of MIDI and its derivatives (R. J. de Groot, R. G. van der Most, and W. J. M. Spaan, J. Virol. 66:5898-5905, 1992). To determine whether translation of the ORF per se is required or whether the encoded polypeptide or a specific sequence is involved, we analyzed sets of related DI RNAs containing different ORFs. After partial deletion of ORF1b and nucleocapsid gene sequences, disruption of the remaining ORF is still lethal; translation of the entire ORF is not essential, however. When a large fragment of the MHV-A59 spike gene, which is not present in any of the MHV-A59 DI RNAs identified so far, was inserted in-frame into a MIDI derivative, translation across this sequence was vital to DI RNA survival. Thus, the translated sequence is irrelevant, indicating that translation per se plays a crucial role in DI virus propagation. Next, it was examined during which step of the viral life cycle translation plays its role. Since the requirement for translation also exists in DI RNA-transfected and MHV-infected cells, it follows that either the synthesis or degradation of DI RNAs is affected by translation.",,"['van der Most, R G', 'Luytjes, W', 'Rutjes, S', 'Spaan, W J']",,,,
,PMC,Identification and characterization of a serine-like proteinase of the murine coronavirus MHV-A59.,,PMC189070,,,"Gene 1 of the murine coronavirus, MHV-A59, encodes approximately 800 kDa of protein products within two overlapping open reading frames (ORFs 1a and 1b). The gene is expressed as a polyprotein that is processed into individual proteins, presumably by virus-encoded proteinases. ORF 1a has been predicted to encode proteins with similarity to viral and cellular proteinases, such as papain, and to the 3C proteinases of the picornaviruses (A. E. Gorbalenya, A. P. Donchenko, V. M. Blinov, and E. V. Koonin, FEBS Lett. 243:103-114, 1989; A. E. Gorbalenya, E. V. Koonin, A. P. Donchenko, and V. M. Blinov, Nucleic Acids Res. 17:4847-4861, 1989). We have cloned into a T7 transcription vector a cDNA fragment containing the putative 3C-like proteinase domain of MHV-A59, along with portions of the flanking hydrophobic domains. The construct was used to express a polypeptide in a combined in vitro transcription-translation system. Major polypeptides with molecular masses of 38 and 33 kDa were detected at early times, whereas polypeptides with molecular masses of 32 and 27 kDa were predominant after 30 to 45 min and appeared to be products of specific proteolysis of larger precursors. Mutations at the putative catalytic histidine and cysteine residues abolished the processing of the 27-kDa protein. Translation products of the pGpro construct were able to cleave the 27-kDa protein in trans from polypeptides expressed from the noncleaving histidine or cysteine mutants. The amino-terminal cleavage of the 27-kDa protein occurred at a glutamine-serine dipeptide as previously predicted. This study provides experimental confirmation that the coronaviruses express an active proteinase within the 3C-like proteinase domain of gene 1 ORF 1a and that this proteinase utilizes at least one canonical QS dipeptide as a cleavage site in vitro.",,"['Lu, Y', 'Lu, X', 'Denison, M R']",,,,
,PMC,Analysis of second-site revertants of a murine coronavirus nucleocapsid protein deletion mutant and construction of nucleocapsid protein mutants by targeted RNA recombination.,,PMC189057,,,"The Alb4 mutant of the coronavirus mouse hepatitis virus (MHV) is both temperature sensitive and thermolabile owing to a deletion in the gene encoding its nucleocapsid (N) protein. The deletion removes 29 amino acids that constitute a putative spacer region preceding the carboxyl-terminal domain of the protein. As a step toward understanding the structure and function of the MHV N protein, we isolated multiple independent revertants of Alb4 that totally or partially regained the ability to form large (wild-type-sized) plaques at the nonpermissive temperature. The N proteins of these revertant viruses concomitantly regained the ability to bind to RNA in vitro at a temperature that was restrictive for RNA binding by Alb4 N protein. Sequence analysis of the N genes of the revertants revealed that each contained a single second-site point mutation that compensated for the effects of the deletion. All reverting mutations were clustered within a stretch of 40 amino acids centered some 80 residues on the amino side of the Alb4 deletion, within a domain to which the RNA-binding activity of N had been previously mapped. By means of a targeted RNA recombination method that we have recently developed, two of the reverting mutations were introduced into a wild-type MHV genomic background. The resulting recombinants were stable and showed no gross phenotypic differences from the wild type. A detailed analysis of one, however, revealed that it was at a selective disadvantage with respect to the wild type.",,"['Peng, D', 'Koetzner, C A', 'Masters, P S']",,,,
,PMC,Formation of brome mosaic virus RNA-dependent RNA polymerase in yeast requires coexpression of viral proteins and viral RNA.,,PMC41813,,,"In this report we show that yeast expressing brome mosaic virus (BMV) replication proteins 1a and 2a and replicating a BMV RNA3 derivative can be extracted to yield a template-dependent BMV RNA-dependent RNA polymerase (RdRp) able to synthesize (-)-strand RNA from BMV (+)-strand RNA templates added in vitro. This virus-specific yeast-derived RdRp mirrored the template selectivity and other characteristics of RdRp from BMV-infected plants. Equivalent extracts from yeast expressing 1a and 2a but lacking RNA3 contained normal amounts of 1a and 2a but had no RdRp activity on BMV RNAs added in vitro. To determine which RNA3 sequences were required in vivo to yield RdRp activity, we tested deletions throughout RNA3, including the 5',3', and intercistronic noncoding regions, which contain the cis-acting elements required for RNA3 replication in vivo. RdRp activity was obtained only from cells expressing 1a, 2a, and RNA3 derivatives retaining both 3' and intercistronic noncoding sequences. Strong correlation between extracted RdRp activity and BMV (-)-strand RNA accumulation in vivo was found for all RNA3 derivatives tested. Thus, extractable in vitro RdRp activity paralleled formation of a complex capable of viral RNA synthesis in vivo. The results suggest that assembly of active RdRp requires not only viral proteins but also viral RNA, either to directly contribute some nontemplate function or to recruit essential host factors into the RdRp complex and that sequences at both the 3'-terminal initiation site and distant internal sites of RNA3 templates may participate in RdRp assembly and initiation of (-)-strand synthesis.",,"['Quadt, R', 'Ishikawa, M', 'Janda, M', 'Ahlquist, P']",,,,
,PMC,Community study of role of viral infections in exacerbations of asthma in 9-11 year old children.,,PMC2549614,,,"OBJECTIVE--To study the association between upper and lower respiratory viral infections and acute exacerbations of asthma in schoolchildren in the community. DESIGN--Community based 13 month longitudinal study using diary card respiratory symptom and peak expiratory flow monitoring to allow early sampling for viruses. SUBJECTS--108 Children aged 9-11 years who had reported wheeze or cough, or both, in a questionnaire. SETTING--Southampton and surrounding community. MAIN OUTCOME MEASURES--Upper and lower respiratory viral infections detected by polymerase chain reaction or conventional methods, reported exacerbations of asthma, computer identified episodes of respiratory tract symptoms or peak flow reductions. RESULTS--Viruses were detected in 80% of reported episodes of reduced peak expiratory flow, 80% of reported episodes of wheeze, and in 85% of reported episodes of upper respiratory symptoms, cough, wheeze, and a fall in peak expiratory flow. The median duration of reported falls in peak expiratory flow was 14 days, and the median maximum fall in peak expiratory flow was 81 l/min. The most commonly identified virus type was rhinovirus. CONCLUSIONS--This study supports the hypothesis that upper respiratory viral infections are associated with 80-85% of asthma exacerbations in school age children.",,"['Johnston, S. L.', 'Pattemore, P. K.', 'Sanderson, G.', 'Smith, S.', 'Lampe, F.', 'Josephs, L.', 'Symington, P.', ""O'Toole, S."", 'Myint, S. H.', 'Tyrrell, D. A.']",,,,
,PMC,"Sequence comparison of porcine respiratory coronavirus isolates reveals heterogeneity in the S, 3, and 3-1 genes.",,PMC189021,,,"Four new porcine respiratory coronavirus (PRCV) isolates were genetically characterized. Subgenomic mRNA patterns and the nucleotide sequences of the 5' ends of the S genes, the open reading frame (ORF) 3/3a genes, and the ORF 3-1/3b genes of these PRCV isolates were determined and compared with those of other PRCV and transmissible gastroenteritis virus (TGEV) isolates. The S, ORF 3/3a, and ORF 3-1/3b genes are under intense study because of their possible roles in determining tissue tropism and virulence. Northern (RNA) blot analysis of subgenomic mRNAs revealed that mRNA 2, which encodes for the S gene, of the PRCV isolates migrated faster than the mRNA 2 of TGEV. The PRCV isolates AR310 and LEPP produced eight subgenomic mRNA species, the same number as produced by the virulent Miller strain of TGEV. However, the PRCV isolates IA1894 and ISU-1 produced only seven subgenomic mRNA species. All four of the PRCV isolates were found to have a large in-frame deletion in the 5' end of the S gene; however, the size and location of the deletion varied. Analysis of the ORF 3/3a gene nucleotide sequences from the four PRCV isolates also showed a high degree of variability in this area. The ORF 3 gene of the PRCV isolates AR310 and LEPP was preceded by a CTAAAC leader RNA-binding site, and the ORF 3 gene was predicted to yield a protein of 72 amino acids, the same size as that of the virulent Miller strain of TGEV. The PRCV isolates AR310 and LEPP are the first PRCV isolates found to have an intact ORF 3 gene. The ORF 3a gene of the PRCV isolate IA1894 was preceded by a CTAAAC leader RNA-binding site and was predicted to yield a truncated protein of 54 amino acids due to a 23-nucleotide deletion. The CTAAAC leader RNA-binding site and ATG start codon of ORF 3 gene of the PRCV isolate ISU-1 were removed because of a 168-nucleotide deletion. Analysis of the ORF 3-1/3b gene nucleotide sequences from the four PRCV nucleotides isolates also showed variability.",,"['Vaughn, E M', 'Halbur, P G', 'Paul, P S']",,,,
,PMC,Poliovirus infection enhances the formation of two ribonucleoprotein complexes at the 3' end of viral negative-strand RNA.,,PMC188994,,,"To identify proteins involved in the formation of replication complexes at the 3' end of poliovirus negative-strand RNA, a combined in vitro biochemical and in vivo genetic approach was used. Five subgenomic cDNA constructs were generated to transcribe different negative-strand RNA fragments. In UV cross-linking assays, distinct differences in binding of proteins in extracts from poliovirus-infected and uninfected cells to virus-specific, radiolabeled transcripts were observed. Two proteins present in extracts from poliovirus-infected cells with approximate molecular masses of 36 and 38 kDa were shown to cross-link to the 3' end of poliovirus negative-strand RNA. Appearance of the 36- and 38-kDa proteins in UV cross-linking assays can be detected 3 to 3.5 h after infection, and cross-linking reaches maximum levels by 5 h after infection. The binding site for the 36-kDa protein overlaps with the computer-predicted loop b region of stem-loop I, the so-called cloverleaf structure, and the RNA sequence of this region is required for efficient binding. Transfection of full-length, positive-sense RNA containing a five-nucleotide substitution (positions 20 to 25) in the loop b region of stem-loop I into tissue culture cells yielded only viral isolates with a reversion at position 24 (U-->C). This finding demonstrates that the wild-type cytidine residue at position 24 is essential for virus replication. RNA binding studies with transcripts corresponding to the 3' end of negative-strand RNA suggest that complex formation with the 36-kDa protein plays an essential role during the viral life cycle.",,"['Roehl, H H', 'Semler, B L']",,,,
,PMC,Localization of antigenic sites of the S glycoprotein of feline infectious peritonitis virus involved in neutralization and antibody-dependent enhancement.,,PMC188981,,,"The S glycoprotein of feline infectious peritonitis virus (FIPV) has been shown to contain the antigenic sites responsible for eliciting both neutralization and antibody-dependent enhancement. To determine the region of S responsible, overlapping DNA fragments spanning the entire S gene were cloned and expressed as fusion proteins by in vitro transcription and translation. Fusion proteins containing relevant epitopes were identified by radioimmunoprecipitation with neutralizing and enhancing FIPV-specific monoclonal antibodies (MAbs). A region spanning residues 509 to 673 reacted with most MAbs tested. Translation in the presence of microsomal membranes did not enhance reactivity, suggesting that glycosylation is not essential for recognition by the MAbs. To localize the antigenic sites further, several MAb-resistant (mar) mutants of FIPV were cloned and sequenced. Amino acid residues that contribute to the neutralizing and enhancing epitopes were localized to two regions, designated A1 and A2, which show partial overlap with the homologous antigenic site A of transmissible gastroenteritis virus. Site A1 contains residues 568 and 591 and is homologous with part of subsite Aa of transmissible gastroenteritis virus. Site A2 contains residues 643, 649, and 656. Double mutations in sites A1 and A2 were found in mar mutants derived from neutralizing and enhancing MAbs 23F4.5 and 18A7.4, while a single mutation in site A2 was found in a mar mutant derived from MAb 24H5.4, which is neutralizing but not enhancing. The data suggest that site A2, which includes residues 643 to 656, is a dominant neutralizing site of FIPV and that sites A1 and A2 may act in concert to induce antibody-dependent enhancement.",,"['Corapi, W V', 'Darteil, R J', 'Audonnet, J C', 'Chappuis, G E']",,,,
,PMC,Yeast virus propagation depends critically on free 60S ribosomal subunit concentration.,,PMC230508,,,"Over 30 MAK (maintenance of killer) genes are necessary for propagation of the killer toxin-encoding M1 satellite double-stranded RNA of the L-A virus. Sequence analysis revealed that MAK7 is RPL4A, one of the two genes encoding ribosomal protein L4 of the 60S subunit. We further found that mutants with mutations in 18 MAK genes (including mak1 [top1], mak7 [rpl4A], mak8 [rpl3], mak11, and mak16) had decreased free 60S subunits. Mutants with another three mak mutations had half-mer polysomes, indicative of poor association of 60S and 40S subunits. The rest of the mak mutants, including the mak3 (N-acetyltransferase) mutant, showed a normal profile. The free 60S subunits, L-A copy number, and the amount of L-A coat protein in the mak1, mak7, mak11, and mak16 mutants were raised to the normal level by the respective normal single-copy gene. Our data suggest that most mak mutations affect M1 propagation by their effects on the supply of proteins from the L-A virus and that the translation of the non-poly(A) L-A mRNA depends critically on the amount of free 60S ribosomal subunits, probably because 60S association with the 40S subunit waiting at the initiator AUG is facilitated by the 3' poly(A).",,"['Ohtake, Y', 'Wickner, R B']",,,,
,PMC,Decoying the cap- mRNA degradation system by a double-stranded RNA virus and poly(A)- mRNA surveillance by a yeast antiviral system.,,PMC230507,,,"The major coat protein of the L-A double-stranded RNA virus of Saccharomyces cerevisiae covalently binds m7 GMP from 5' capped mRNAs in vitro. We show that this cap binding also occurs in vivo and that, while this activity is required for expression of viral information (killer toxin mRNA level and toxin production) in a wild-type strain, this requirement is suppressed by deletion of SKI1/XRN1/SEP1. We propose that the virus creates decapped cellular mRNAs to decoy the 5'-->3' exoribonuclease specific for cap- RNA encoded by XRN1. The SKI2 antiviral gene represses the copy numbers of the L-A and L-BC viruses and the 20S RNA replicon, apparently by specifically blocking translation of viral RNA. We show that SKI2, SKI3, and SKI8 inhibit translation of electroporated luciferase and beta-glucuronidase mRNAs in vivo, but only if they lack the 3' poly(A) structure. Thus, L-A decoys the SKI1/XRN1/SEP1 exonuclease directed at 5' uncapped ends, but translation of the L-A poly(A)- mRNA is repressed by Ski2,3,8p. The SKI2-SKI3-SKI8 system is more effective against cap+ poly(A)- mRNA, suggesting a (nonessential) role in blocking translation of fragmented cellular mRNAs.",,"['Masison, D C', 'Blanc, A', 'Ribas, J C', 'Carroll, K', 'Sonenberg, N', 'Wickner, R B']",,,,
,PMC,Virus receptors: implications for pathogenesis and the design of antiviral agents.,,PMC172860,,,"A virus initiates infection by attaching to its specific receptor on the surface of a susceptible host cell. This prepares the way for the virus to enter the cell. Consequently, the expression of the receptor on specific cells and tissues of the host is a major determinant of the route of entry of the virus into the host and of the patterns of virus spread and pathogenesis in the host. This review emphasizes the virus-receptor interactions of human immunodeficiency virus, the rhinoviruses, the herpesviruses, and the coronaviruses. These interactions are often found to be complex and dynamic, involving multiple sites or factors on both the virus and the host cell. Also, the receptor may play an important role in virus entry per se in addition to its role in virus binding. In the cases of human immunodeficiency virus and the rhinoviruses, ingenious approaches to therapeutic strategies based on inhibiting virus attachment and entry are under development and in clinical trials.",,"Norkin, L C",,,,
,PMC,A pilot study of infectious intestinal disease in England.,,PMC2271284,,,"Pilot studies to test methods to determine the incidence, agents, risk factors and socioeconomic costs of infectious intestinal disease (IID) in England were carried out as recommended by the Committee on the Microbiological Safety of Food (the Richmond Committee) by eight general practices. There were case control and enumeration studies of patients presenting to general practice with IID, a population-based prospective cohort study, and a survey of socioeconomic costs of cases of IID. Information on risk factors was obtained by questionnaire (self-administered compared with interview) and a stool sample was requested on all cases and controls. Response rates in the GP case control study were 75% for case questionnaires and 74% for stools; for controls the figures were 70% and 68% respectively. The acceptance rate into the cohort study was 49%; this was significantly higher where phone contact was made. The rate was similar if recruitment was by individual or household. Follow-up of the cohort by negative reporting was complete for up to 6 months. Direct postage by subject was required to obtain fresh stool specimens. Estimates were obtained of presentation rates of IID and the distribution of risk factors which were used to plan the main study. The pilot study demonstrated that it is possible to undertake a national study based in general practice to determine the incidence of IID in the population and presenting to GPs and its agents, risk factors and costs.",,"['Roderick, P.', 'Wheeler, J.', 'Cowden, J.', 'Sockett, P.', 'Skinner, R.', 'Mortimer, P.', 'Rowe, B.', 'Rodriques, L.']",,,,
,PMC,Predominance of MHC class II-restricted CD4+ cytotoxic T cells against mouse hepatitis virus A59.,,PMC1415158,,,"Coronavirus-induced acute hepatitis is a complex event and the role of different components of the immune system with regard to defined viral proteins and the course of the infection is not yet clear. We have analysed the cytotoxic T-lymphocyte (CTL) response in mouse hepatitis virus (MHV-A59) infection. Surprisingly, we detected only a very clear virus-specific major histocompatibility complex (MHC) class II-restricted cytotoxicity in mice infected with MHV-A59. We found no evidence of activation of the classical CD8+ MHC class I-restricted CTL. The virus-specific CD4+ CTL derived from two different mouse strains having different MHC haplotypes recognized the same immunodominant epitope. This epitope, comprising the amino acid residues 329-343 of the viral S-glycoprotein, was recognized both at the polyclonal level and by virus-specific CTL clones. Transfer studies using a MHV-A59-specific CD4+ CTL clone showed significant protection against a lethal challenge with MHV-A59, implicating that these CD4+ CTL play a pivotal role in the protection against MHV-A59 infections.",,"['Heemskerk, M H', 'Schoemaker, H M', 'Spaan, W J', 'Boog, C J']",,,,
,PMC,Effect of experimental influenza A virus infection on isolation of Streptococcus pneumoniae and other aerobic bacteria from the oropharynges of allergic and nonallergic adult subjects.,,PMC173127,,,"Intranasal challenge with both influenza A virus and Streptococcus pneumoniae promotes otitis media with S. pneumoniae in chinchillas. We investigated whether influenza A virus infection promotes oropharyngeal colonization with S. pneumoniae and other middle ear pathogens by selectively inhibiting commensal bacteria. On study day 0, 12 allergic and 15 nonallergic adult subjects were intranasally inoculated with influenza A/Kawasaki (H1N1) virus. Every subject was infected with the virus as demonstrated by nasal shedding or seroconversion. Average upper respiratory symptom scores and nasal secretion weights from the entire subject group were elevated between days 2 and 6 (acute phase) and were not significantly different between allergic and nonallergic subjects. S. pneumoniae was not isolated from any subject prior to the virus challenge but was isolated in heavy density from 4 (15%) subjects on day 6 (P = 0.055). Staphylococcus aureus was isolated more frequently from the nonallergic subjects than from the allergic subjects on days 2 (80 versus 25%, respectively) 4, (67 versus 17%, respectively), and 6 (73 versus 25%, respectively) (P < 0.05). The isolation rates of other middle ear pathogens were not significantly different before virus challenge and during the acute and resolution phases (days 27 to 30) of the experimental infection for the entire subject group or either the allergic or nonallergic subgroup. Densities and isolation rates of commensal bacteria from the entire subject group were similar throughout the observational period. These results suggest that the virus infection promoted S. pneumoniae colonization of the oropharynx and that nonallergic persons may be more vulnerable to colonization with S. aureus than allergic persons. The altered colonization rates were not attributed to inhibition of commensal bacteria.",,"['Wadowsky, R M', 'Mietzner, S M', 'Skoner, D P', 'Doyle, W J', 'Fireman, P']",,,,
,PMC,Molecular characterization of the 3' terminus of the simian hemorrhagic fever virus genome.,,PMC188954,,,"The 3' end of the simian hemorrhagic fever virus (SHFV) single-stranded RNA genome was cloned and sequenced. Adjacent to the 3' poly(A) tract, we identified a 76-nucleotide noncoding region preceded by two overlapping reading frames (ORFs). The ultimate 3' ORF of the viral genome encodes the capsid protein, and the penultimate ORF encodes the smallest SHFV envelope protein. These two ORFs overlap each other by 26 nucleotides. Northern (RNA) blot hybridization analyses of cytoplasmic RNA extracts from SHFV-infected MA-104 cells with gene-specific probes revealed the presence of full-length genomic RNA as well as six subgenomic SHFV-specific mRNA species. The subgenomic mRNAs are 3' coterminal. In its virion morphology and size, genome structure and length, and replication strategy, SHFV is most similar to lactate dehydrogenase-elevating virus, equine arteritis virus, and porcine reproductive and respiratory syndrome virus.",,"['Godeny, E K', 'Zeng, L', 'Smith, S L', 'Brinton, M A']",,,,
,PMC,Two murine coronavirus genes suffice for viral RNA synthesis.,,PMC188902,,,"We identified two mouse hepatitis virus (MHV) genes that suffice for MHV RNA synthesis by using an MHV-JHM-derived defective interfering (DI) RNA, DIssA. DIssA is a naturally occurring self-replicating DI RNA with nearly intact genes 1 and 7. DIssA interferes with most MHV-JHM-specific RNA synthesis, except for synthesis of mRNA 7, which encodes N protein; mRNA 7 synthesis is not inhibited by DIssA. Coinfection of MHV-JHM containing DIssA DI particles and an MHV-A59 RNA- temperature-sensitive mutant followed by subsequent passage of virus at the permissive temperature resulted in elimination of most of the MHV-JHM helper virus. Analysis of intracellular RNAs at the nonpermissive temperature demonstrated efficient synthesis of DIssA and mRNA 7 but not of the helper virus mRNAs. Oligonucleotide fingerprinting analysis demonstrated that the structure of mRNA 7 was MHV-JHM specific and therefore must have been synthesized from the DIssA template RNA. Sequence analysis revealed that DIssA lacks a slightly heterogeneous sequence, which is found in wild-type MHV from the 3' one-third of gene 2-1 to the 3' end of gene 6. Northern (RNA) blot analysis of intracellular RNA species and virus-specific protein analysis confirmed the sequence data. Replication and transcription of another MHV DI RNA were supported in DIssA-replicating cells. Because the products of genes 2 and 2-1 are not essential for MHV replication, we concluded that expression of gene 1 proteins and N protein was sufficient for MHV RNA replication and transcription.",,"['Kim, K H', 'Makino, S']",,,,
,PMC,Specific binding of host cellular proteins to multiple sites within the 3' end of mouse hepatitis virus genomic RNA.,,PMC188866,,,"The initial step in mouse hepatitis virus (MHV) RNA replication is the synthesis of negative-strand RNA from a positive-strand genomic RNA template. Our approach to begin studying MHV RNA replication is to identify the cis-acting signals for RNA synthesis and the proteins which recognize these signals at the 3' end of genomic RNA of MHV. To determine whether host cellular and/or viral proteins interact with the 3' end of the coronavirus genome, an RNase T1 protection/gel mobility shift electrophoresis assay was used to examine cytoplasmic extracts from mock- and MHV-JHM-infected 17Cl-1 murine cells for the ability to form complexes with defined regions of the genomic RNA. We demonstrated the specific binding of host cell proteins to multiple sites within the 3' end of MHV-JHM genomic RNA. By using a set of RNA probes with deletions at either the 5' or 3' end or both ends, two distinct binding sites were located. The first protein-binding element was mapped in the 3'-most 42 nucleotides of the genomic RNA [3' (+42) RNA], and the second element was mapped within an 86-nucleotide sequence encompassing nucleotides 171 to 85 from the 3' end of the genome (171-85 RNA). A single potential stem-loop structure is predicted for the 3' (+)42 RNA, and two stem-loop structures are predicted for the 171-85 RNA. Proteins interacting with these two elements were identified by UV-induced covalent cross-linking to labeled RNAs followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The RNA-protein complex formed with the 3'-most 42 nucleotides contains approximately five host polypeptides, a highly labeled protein of 120 kDa and four minor species with sizes of 103, 81, 70, and 55 kDa. The second protein-binding element, contained within a probe representing nucleotides 487 to 85 from the 3' end of the genome, also appears to bind five host polypeptides, 142, 120, 100, 55, and 33 kDa in size, with the 120-kDa protein being the most abundant. The RNA-protein complexes observed with MHV-infected cells in both RNase protection/gel mobility shift and UV cross-linking assays were identical to those observed with uninfected cells. The possible involvement of the interaction of host proteins with the viral genome during MHV replication is discussed.",,"['Yu, W', 'Leibowitz, J L']",,,,
,PMC,Stimulation of interferon and cytokine gene expression by imiquimod and stimulation by Sendai virus utilize similar signal transduction pathways.,,PMC230449,,,"The imidazoquinolineamine derivative 1-(2-methyl propyl)-1H-imidazole [4,5-c]quinoline-4-amine (imiquimod) has been shown to induce alpha interferon (IFN-alpha) synthesis both in vivo and in peripheral blood mononuclear cells in vitro. In this study, we show that, in these cells, imiquimod induces expression of several IFNA genes (IFNA1, IFNA2, IFNA5, IFNA6, and IFNA8) as well as the IFNB gene. Imiquimod also induced the expression of interleukin (IL)-6, IL-8, and tumor necrosis factor alpha genes. Expression of all these genes was transient, independent of cellular protein synthesis, and inhibited in the presence of tyrosine kinase and protein kinase C inhibitors. Infection with Sendai virus led to expression of a similar set of cytokine genes and several of the IFNA genes. Imiquimod stimulates binding of several induction-specific nuclear complexes: (i) the NF-kappa B-specific complexes binding to the kappa B enhancer present in the promoters of all cytokine genes, but not in IFNA genes, and (ii) the complex(es) binding to the A4F1 site, 5'-GTAAAGAAAGT-3', conserved in the inducible element of IFNA genes. These results indicate that imiquimod, similar to viral infection, stimulates expression of a large number of cytokine genes, including IFN-alpha/beta, and that the signal transduction pathway induced by both of these stimuli requires tyrosine kinase and protein kinase activity.",,"['Megyeri, K', 'Au, W C', 'Rosztoczy, I', 'Raj, N B', 'Miller, R L', 'Tomai, M A', 'Pitha, P M']",,,,
,PMC,Avridine-induced arthritis in rats; a T cell-dependent chronic disease influenced both by MHC genes and by non-MHC genes.,,PMC1534209,,,"Avridine is a potent synthetic adjuvant that can induce arthritis is most rat strains. The clinical appearance and histopathology of avridine-induced arthritis show great similarity to other arthritis models such as collagen-induced arthritis. In LEW and DA rats the avridine-induced arthritis is severe and long lasting. To investigate a possible genetic influence on the disease we compared LEW, DA and E3 rats, which are of different genetic origins, for their ability to develop arthritis after injection of a low dose of avridine (1.5 mg/rat). The E3 rat was shown to be resistant, whereas all of the DA rats developed arthritis. Recombinant inbred strains derived from DA and E3 parentals varied in susceptibility to avridine. Only strains sharing RT1av1 with DA developed arthritis, indicating a role for the MHC genes. The MHC association was further analysed in a series of Lewis congenic strains using the 1.5 mg avridine dose. All strains developed arthritis. LEW.1C and LEW.1W developed only acute arthritis, whereas LEW.1A, LEW, LEW.1D, LEW.1N and LEW.1F developed chronic arthritis. In particular, the LEW.1F rats developed a chronic severe arthritis of high incidence. The chronic arthritis showed an active, erosive joint inflammation several months after induction. Nude rats are resistant to avridine-induced arthritis, indicating a T cell dependence of the disease which supports the importance of MHC. However, non-MHC genes are also crucial to arthritis development. Recombinants between DA and E3, sharing RT1av1 with DA, showed either a lower incidence or a lower severity of disease than the DA rats. The E3 rat and the recombinants with RT1u were completely resistant, whereas LEW.1W, also RT1u, were highly susceptible.",,"['Vingsbo, C', 'Jonsson, R', 'Holmdahl, R']",,,,
,PMC,"Detection of feline coronavirus RNA in feces, tissues, and body fluids of naturally infected cats by reverse transcriptase PCR.",,PMC228014,,,"A nested reverse transcriptase PCR (RT-nPCR) was developed for the detection of feline coronavirus (FCoV) RNA in the feces, tissues, and body fluids of infected cats. The RT-nPCR was targeted to the highly conserved 3'-untranslated region of the viral genome and will detect most, if not all, feline coronaviruses in the field. With the RT-nPCR, FCoV RNA was detected in plasma samples from experimentally infected cats as early as 2 days postinoculation. FCoV RNA was also detected in serum, plasma, or ascitic fluid samples from 14 of 18 cats (78%) with naturally occurring feline infectious peritonitis (FIP). The use of RT-PCR for FIP diagnosis is limited because of the occurrence of apparently healthy FCoV carriers. These asymptomatic cats shed the virus in the feces and, in a number of cases, also had detectable virus in the plasma. Because of the nature of FCoV infections, our RT-PCR assay with plasma or serum cannot be used to establish a definite diagnosis of FIP. However, this assay does provide a new means to identify asymptomatic FCoV carriers. As such, RT-nPCR will be of use to screen cats before their introduction into FCoV-free catteries. Moreover, this assay provides an important tool to study the epidemiology of FCoV.",,"['Herrewegh, A A', 'de Groot, R J', 'Cepica, A', 'Egberink, H F', 'Horzinek, M C', 'Rottier, P J']",,,,
,PMC,Detection of enteroviruses and rhinoviruses in clinical specimens by PCR and liquid-phase hybridization.,,PMC228007,,,"A sensitive method based on PCR followed by liquid-phase hybridization for detection of enterovirus and rhinovirus RNAs in clinical specimens and cell culture supernatants is described. RNA was extracted from stool samples, throat swabs, nasopharyngeal aspirates, cerebrospinal fluid, urine, and plasma with a commercial phenol-guanidinium-chloroform reagent and purified on a polysulfone membrane, on which the reverse transcriptase reaction was also done. Two sets of oligonucleotide primers from the 5' noncoding region of picornaviruses were selected for DNA amplification of 153-bp (enterovirus) and 120-bp (rhinovirus) regions. Double-stranded amplicons were digested into single strands with T7 gene 6 exonuclease and quantitated by an assay using a europium-labeled probe, streptavidin- and biotinylated probe-coated microtitration wells, and time-resolved fluorometry. The sensitivity of the assay was about one template molecule when purified coxsackievirus A9 RNA was used. All enterovirus prototype strains, except echoviruses 22 and 23, and clinical isolates grown in cell culture or suckling mice were strongly positive by the enterovirus PCR-hybridization, as were selected prototype strains and untyped isolates of rhinoviruses by the rhinovirus PCR-hybridization. In a series of 100 clinical specimens tested, the results for 92 agreed with virus culture results. The detection method described will be useful in etiopathogenic studies on enteroviruses and rhinoviruses.",,"['Halonen, P', 'Rocha, E', 'Hierholzer, J', 'Holloway, B', 'Hyypiä, T', 'Hurskainen, P', 'Pallansch, M']",,,,
,PMC,Interleukin-12 gene expression after viral infection in the mouse.,,PMC188815,,,"Interleukin-12 is a lymphokine that triggers gamma interferon secretion by various cells and differentiation of T-helper lymphocytes towards the Th1 subtype. Since viruses are potent inducers of gamma interferon production and elicit immune responses most probably mediated by Th1 cells, like B-cell immunoglobulin G2a secretion, we analyzed interleukin-12 message expression after infection of mice with lactate dehydrogenase-elevating virus, mouse hepatitis virus, and mouse adenovirus. Our results indicated that the message for the p40 component of interleukin-12 was transiently increased shortly after infection. Interleukin-12 was expressed mainly by macrophages. Therefore, production of interleukin-12 might constitute the initial event that would determine the subsequent characteristics of the immune response elicited by viral infections.",,"['Coutelier, J P', 'Van Broeck, J', 'Wolf, S F']",,,,
,PMC,Interactions between the cytoplasmic proteins and the intergenic (promoter) sequence of mouse hepatitis virus RNA: correlation with the amounts of subgenomic mRNA transcribed.,,PMC188761,,,"Previous studies suggested that coronavirus RNA transcription involves interaction between leader RNA and the intergenic (IG) sequences, probably via protein-RNA interactions (X. M. Zhang, C.-L. Liao, and M. M. C. Lai, J. Virol., 68:4738-4746, 1994; X. M. Zhang and M. M. C. Lai, J. Virol., 68:6626-6633, 1994). To determine whether cellular proteins are involved in this process, we performed UV cross-linking experiments using cytoplasmic extracts of uninfected cells and the IG (promoter) sequence between genes 6 and 7 (IG7) and the 5' untranslational region of mouse hepatitis virus genomic RNA. We demonstrated that three different cellular proteins (p70, p48, and p35/38) bound to the promoter sequence of the template RNA. Deletion analyses of the template RNA mapped the binding site of p35/38 at the consensus transcription initiation signal. In contrast, the binding of p70 and p48 was less specific. p35/38 is the same protein as the one previously identified to bind to the complementary strand of the leader RNA; its binding affinity to the leader was approximately 15 times stronger than that to IG7. Site-directed mutagenesis of the IG sequence revealed that mutations in the consensus sequence of IG7 (UCUAAUCUAAAC to UCGAAAC and GCUAAAG), which resulted in reduced subgenomic mRNA transcription, also caused correspondingly reduced levels of p35/38 binding. These results demonstrated that the extent of protein binding to the IG sequences correlated with the amounts of subgenomic mRNAs transcribed from the IG site. These studies suggest that these RNA-binding proteins are involved in coronavirus RNA transcription and may represent transcription factors.",,"['Zhang, X', 'Lai, M M']",,,,
,PMC,Effects of topical capsaicin in seasonal allergic rhinitis.,,PMC1021182,,,"BACKGROUND--Mucosal exudation (luminal entry) of bulk plasma is a key feature of airway defence and inflammation. In guinea pig and rat airways this response is readily produced by neurogenic irritants, notably capsaicin. Thus ""neurogenic airway inflammation"" has become an established concept. The present study examines whether capsaicin also produces mucosal exudation of plasma in human nasal airways both in health and disease (seasonal allergic rhinitis). METHODS--Pain-producing concentrations of capsaicin (30-300 ng/ml) were applied to the nasal mucosal surface both before and late into the pollen season. Levels of albumin in nasal lavage fluid were measured as an index of mucosal exudation of plasma. In a separate group of patients with seasonal allergic rhinitis nasal challenge with an exudative concentration of histamine was carried out before the birch pollen season and concentrations of albumin in lavage fluid were measured. RESULTS--Pollen counts and symptom scores revealed a mild pollen season. Capsaicin produced considerable nasal pain and this response was augmented late into the season when capsaicin also produced nasal blockage. However, capsaicin failed to produce any mucosal exudation of plasma either before or late into the pollen season. The exudative effect of histamine was confirmed. CONCLUSIONS--The augmented pain response to capsaicin suggests that a sensory nerve hyperresponsiveness may characterise allergic airways disease. In contrast to the effects on animal airways, capsaicin failed to produce mucosal exudation of plasma in the human nasal airway. The animal based neurogenic inflammation concept is therefore not valid for the human nasal airway, not even in inflamed airways when a neural hyperresponsiveness has developed.",,"['Greiff, L.', 'Svensson, C.', 'Andersson, M.', 'Persson, C. G.']",,,,
,PMC,Structural and functional studies of retroviral RNA pseudoknots involved in ribosomal frameshifting: nucleotides at the junction of the two stems are important for efficient ribosomal frameshifting.,,PMC398151,,,"Ribosomal frameshifting, a translational mechanism used during retroviral replication, involves a directed change in reading frame at a specific site at a defined frequency. Such programmed frameshifting at the mouse mammary tumor virus (MMTV) gag-pro shift site requires two mRNA signals: a heptanucleotide shifty sequence and a pseudoknot structure positioned downstream. Using in vitro translation assays and enzymatic and chemical probes for RNA structure, we have defined features of the pseudoknot that promote efficient frameshifting. Heterologous RNA structures, e.g. a hairpin, a tRNA or a synthetic pseudoknot, substituted downstream of the shifty site fail to promote frameshifting, suggesting that specific features of the MMTV pseudoknot are important for function. Site-directed mutations of the MMTV pseudoknot indicate that the pseudoknot junction, including an unpaired adenine nucleotide between the two stems, provides a specific structural determinant for efficient frameshifting. Pseudoknots derived from other retroviruses (i.e. the feline immunodeficiency virus and the simian retrovirus type 1) also promote frameshifting at the MMTV gag-pro shift site, dependent on the same structure at the junction of the two stems.",,"['Chen, X', 'Chamorro, M', 'Lee, S I', 'Shen, L X', 'Hines, J V', 'Tinoco, I', 'Varmus, H E']",,,,
,PMC,Papillomavirus capsid binding and uptake by cells from different tissues and species.,,PMC188663,,,"The inability of papillomaviruses (PV) to replicate in tissue culture cells has hampered the study of the PV life cycle. We investigated virus-cell interactions by the following two methods: (i) using purified bovine PV virions or human PV type 11 (HPV type 11) virus-like particles (VLP) to test the binding to eukaryotic cells and (ii) using different VLP-reporter plasmid complexes of HPV6b, HPV11 L1 or HPV11 L1/L2, and HPV16 L1 or HPV16 L1/L2 to study uptake of particles into different cell lines. Our studies showed that PV capsids bind to a broad range of cells in culture in a dose-dependent manner. Binding of PV capsids to cells can be blocked by pretreating the cells with the protease trypsin. Penetration of PV into cells was monitored by using complexes in which the purified PV capsids were physically linked to DNA containing the gene for beta-galactosidase driven by the human cytomegalovirus promoter. Expression of beta-galactosidase occurred in < 1% of the cells, and the efficiency of PV receptor-mediated gene delivery was greatly enhanced (up to 10 to 20% positive cells) by the use of a replication-defective adenovirus which promotes endosomal lysis. The data generated by this approach further confirmed the results obtained from the binding assays, showing that PV enter a wide range of cells and that these cells have all functions required for the uptake of PV. Binding and uptake of PV particles can be blocked by PV-specific antisera, and different PV particles compete for particle uptake. Our results suggest that the PV receptor is a conserved cell surface molecule(s) used by different PV and that the tropism of infection by different PV is controlled by events downstream of the initial binding and uptake.",,"['Müller, M', 'Gissmann, L', 'Cristiano, R J', 'Sun, X Y', 'Frazer, I H', 'Jenson, A B', 'Alonso, A', 'Zentgraf, H', 'Zhou, J']",,,,
,PMC,Interaction of mouse hepatitis virus (MHV) spike glycoprotein with receptor glycoprotein MHVR is required for infection with an MHV strain that expresses the hemagglutinin-esterase glycoprotein.,,PMC188656,,,"In addition to the spike (S) glycoprotein that binds to carcinoembryonic antigen-related receptors on the host cell membrane, some strains of mouse coronavirus (mouse hepatitis virus [MHV]) express a hemagglutinin esterase (HE) glycoprotein with hemagglutinating and acetylesterase activity. Virions of strains that do not express HE, such as MHV-A59, can infect mouse fibroblasts in vitro, showing that the HE glycoprotein is not required for infection of these cells. The present work was done to study whether interaction of the HE glycoprotein with carbohydrate moieties could lead to virus entry and infection in the absence of interaction of the S glycoprotein with its receptor glycoprotein, MHVR. The DVIM strain of MHV expresses large amounts of HE glycoprotein, as shown by hemadsorption, acetylesterase activity, and immunoreactivity with antibodies directed against the HE glycoprotein of bovine coronavirus. A monoclonal anti-MHVR antibody, MAb-CC1, blocks binding of virus S glycoprotein to MHVR and blocks infection of MHV strains that do not express HE. MAb-CC1 also prevented MHV-DVIM infection of mouse DBT cells and primary mouse glial cell cultures. Although MDCK-I cells express O-acetylated sialic acid residues on their plasma membranes, these canine cells were resistant to infection with MHV-A59 and MHV-DVIM. Transfection of MDCK-I cells with MHVR cDNA made them susceptible to infection with MHV-A59 and MHV-DVIM. Thus, the HE glycoprotein of an MHV strain did not lead to infection of cultured murine neural cells or of nonmurine cells that express the carbohydrate ligand of the HE glycoprotein. Therefore, interaction of the spike glycoprotein of MHV with its carcinoembryonic antigen-related receptor glycoprotein is required for infectivity of MHV strains whether or not they express the HE glycoprotein.",,"['Gagneten, S', 'Gout, O', 'Dubois-Dalcq, M', 'Rottier, P', 'Rossen, J', 'Holmes, K V']",,,,
,PMC,Identification of the murine coronavirus p28 cleavage site.,,PMC188646,,,"Mouse hepatitis virus strain A59 encodes a papain-like cysteine proteinase (PLP-1) that, during translation of ORF1a, cleaves p28 from the amino terminus of the growing polypeptide chain. In order to determine the amino acid sequences surrounding the p28 cleavage site, the first 4.6 kb of murine hepatitis virus strain A59 ORF1a was expressed in a cell-free transcription-translation system. Amino-terminal radiosequencing of the resulting downstream cleavage product demonstrated that cleavage occurs between Gly-247 and Val-248. Site-directed mutagenesis of amino acids surrounding the p28 cleavage site revealed that substitutions of Arg-246 (P2) and Gly-247 (P1) nearly eliminated cleavage of p28. Single-amino-acid substitutions of other residues between P7 and P2' were generally permissive for cleavage, although a few changes did greatly reduce proteolysis. The relationship between the p28 cleavage site and other viral and cellular papain proteinase cleavage sites is discussed.",,"['Hughes, S A', 'Bonilla, P J', 'Weiss, S R']",,,,
,PMC,Mouse hepatitis virus-specific cytotoxic T lymphocytes protect from lethal infection without eliminating virus from the central nervous system.,,PMC188629,,,"Acute infection of the central nervous system by the neurotropic JHM strain of mouse hepatitis virus (JHMV) induces nucleocapsid protein specific cytotoxic T lymphocytes (CTL) not found in the periphery (S. Stohlman, S. Kyuwa, J. Polo, D. Brady, M. Lai, and C. Bergmann, J. Virol. 67:7050-7059, 1993). Peripheral induction of CTL specific for the nucleocapsid protein of JHMV by vaccination with recombinant vaccinia viruses was unable to provide significant protection to a subsequent lethal virus challenge. By contrast, the transfer of nucleoprotein-specific CTL protected mice from a subsequent lethal challenge by reducing virus replication within the central nervous system, demonstrating the importance of the CTL response to this epitope in JHMV infection. Transfer of these CTL directly into the central nervous system was at least 10-fold more effective than peripheral transfer. Histological analysis indicated that the CTL reduced virus replication in ependymal cells, astrocytes, and microglia. Although the CTL were relatively ineffective at reducing virus replication in oligodendroglia, survivors showed minimal evidence of virus persistence within the central nervous system and no evidence of chronic ongoing demyelination.",,"['Stohlman, S A', 'Bergmann, C C', 'van der Veen, R C', 'Hinton, D R']",,,,
,PMC,Spread of a neurotropic coronavirus to spinal cord white matter via neurons and astrocytes.,,PMC188623,,,"Mouse hepatitis virus strain JHM (MHV-JHM) causes a chronic encephalomyelitis in susceptible mice, with histological evidence of demyelination in the spinal cord. After intranasal inoculation, virus spreads retrogradely to several brain structures along neuroanatomic projections to the main olfactory bulb. In the absence of experimental intervention, mice become moribund before the spinal cord is infected. In this study, infusions of anti-MHV neutralizing monoclonal antibodies were administered to protect mice from the MHV-JHM-induced acute encephalitis and to allow survival until virus spread to the spinal cord. Under these conditions, virus was observed to enter specific layers (primarily laminae V to VII) in the gray matter of the upper spinal cord, consistent with transneuronal spread. While the brain structures which are the sources for virus spread to the spinal cord cannot be determined with certainty, the ventral reticular nucleus is likely to be important since it is consistently and extensively labeled in all mice and receives projections from subsequently infected areas of the spinal cord. After initial entry into the gray matter, virus rapidly spread to the white matter of the spinal cord. During the early stages of this process, extensive infection of astrocytes was noted, suggesting that cell-to-cell spread via these glial cells is an important part of this process. Reports from other laboratories using cultured cells strongly suggested that astrocytes serve as important regulators of oligodendrocyte function and, by extrapolation, have a major role in vivo in the processes of both demyelination and remyelination. Thus, our results not only outline the probable pathway used by MHV-JHM to infect the white matter of the spinal cord but also, with the assumption that infection of astrocytes leads to subsequent dysfunction, raise the possibility that infection of these cells contributes to the demyelinating process.",,"['Sun, N', 'Perlman, S']",,,,
,PMC,Molecular dissection of the pseudoknot governing the translational regulation of Escherichia coli ribosomal protein S15.,,PMC306625,,,"The ribosomal protein S15 controls its own translation by binding to a mRNA region overlapping the ribosome binding site. That region of the mRNA can fold in two mutually exclusive conformations that are in dynamic equilibrium: a structure with two hairpins and a pseudoknot. A mutational analysis provided evidence for the existence and requirement of the pseudoknot for translational control in vivo and S15 recognition in vitro. In this study, we used chemical probing to analyze the structural consequences of mutations and their effect on the stem-loop/pseudoknot equilibrium. Interactions between S15 and the pseudoknot structure were further investigated by footprinting experiments. These data, combined with computer modelling and the previously published data on S15 binding and in vivo control, provide important clues on pseudoknot formation and S15 recognition. An unexpected result is that the relevant control element, here the pseudoknot form, can exist in a variety of topologically equivalent structures recognizable and shapable by S15. S15 sits on the deep groove of the co-axial stack and makes contacts with both stems, shielding the bridging adenine. The only specific sequence determinants are found in the helix common to the pseudoknot and the hairpin structures.",,"['Philippe, C', 'Bénard, L', 'Portier, C', 'Westhof, E', 'Ehresmann, B', 'Ehresmann, C']",,,,
,PMC,Passive protection of piglets by recombinant baculovirus induced transmissible gastroenteritis virus specific antibodies.,,PMC1263737,,,"Sera of pigs immunized with parts of the transmissible gastroenteritis virus (TGEV) spike (S) protein expressed by recombinant baculoviruses were tested, together with a TGEV hyperimmune antiserum, for their abilities to protect three-day-old piglets against TGEV infection. The piglets were infected with virulent TGEV and the sera were given orally 3 h before infection, together with the virus, and every 6 h postinfection during the 30 h of the experiment. Virus shedding was monitored by TGEV isolation from rectal swab samples. The sera containing antibodies induced by the complete S protein or the amino terminal half of the S protein showed protective properties, indicated by delayed onset of clinical signs and virus shedding, similar to the TGEV hyperimmune serum. Those immune sera containing antibodies induced by shorter recombinant proteins were not protective.",,"['Tuboly, T', 'Nagy, E', 'Derbyshire, J B']",,,,
,PMC,Effect of time of exposure to rat coronavirus and Mycoplasma pulmonis on respiratory tract lesions in the Wistar rat.,,PMC1263735,,,"The effects of time of exposure on the progression of pulmonary lesions in rats inoculated with Mycoplasma pulmonis and the rat coronavirus, sialodacryoadenitis virus (SDAV) were studied, using six groups of 18 SPF Wistar rats (n = 108). Rats were inoculated intranasally as follows: Group 1, sterile medium only; Group 2, sterile medium followed one week later by 150 TCID50 SDAV; Group 3, sterile medium followed by 10(5.7) colony forming units of M. pulmonis; Group 4, SDAV followed one week later by M. pulmonis; Group 5, M. pulmonis followed one week later by SDAV; Group 6, M. pulmonis followed two weeks later by SDAV. Six rats from each group were euthanized at one, two and three weeks after the final inoculation. In a separate experiment, six additional animals were inoculated in each of groups 3, 5 and 6 (n = 18) and were sampled at five weeks after they had received M. pulmonis. Bronchoalveolar lavage and quantitative lung mycoplasma cultures were conducted on two-thirds of the rats. Histopathological examination and scoring of lesion severity were performed on all animals. Based on the prevalence and extent of histopathological lesions, bronchoalveolar lavage cell numbers, neutrophil differential cell counts and the isolation of M. pulmonis, the most severe disease occurred in the groups that received both agents. There was no significant difference in lesion severity between the groups receiving both agents other than in those examined during the acute stages of SDAV infection. Based on these results, it is evident that SDAV enhances lower respiratory tract disease in Wistar rats whether exposure occurs at one week prior to or at various intervals following M. pulmonis infections.",,"['Schunk, M K', 'Percy, D H', 'Rosendal, S']",,,,
,PMC,A seroepidemiological study of the importance in cow-calf pairs of respiratory and enteric viruses in beef operations from northwestern Quebec.,,PMC1263730,,,"Serum antibody analyses for bovine herpesvirus type 1 (BHV-1), bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), bovine coronavirus (BCV), and bovine rotavirus (BRV) were performed on 527 randomly selected cows, before calving, and on 407 three-week-old calves. In cows and calves, BCV and BRV were the most seroprevalent viruses (80% to 100% according to virus and vaccination status). Bovine respiratory syncytial virus was the least seroprevalent in the cows, independent of the vaccination status. In nonvaccinated cows the seroprevalence to BRSV was 36.7%, and 53.5% in cows vaccinated less than two weeks prior to collecting blood, and 67.6% in cows vaccinated two weeks or more prior to blood collection. In their calves, BHV-1 was the least seroprevalent, independent of the vaccination status. The serological status and antibody titers in calves were generally associated with those of the dam. The occurrence of respiratory diseases in the calves was associated with cow and calf serological profiles (BHV-1, BRSV and BCV in the nonvaccinated group, BHV-1, BVDV and BCV in the vaccinated group). The occurrence of diarrhea was not associated with cow and calf serological profiles but was negatively associated with high level calf serum IgG in the nonvaccinated group (odds ratio = 0.73). Bovine coronavirus and BRV were shed by 1.4% and 4.9% of calves in the nonvaccinated group, and by 0% and 9.9% of calves in the vaccinated group, respectively. Bovine rotavirus shedding was associated with fecal diarrheic consistency at the moment of fecal sampling but not with previous occurrence of diarrhea.",,"['Ganaba, R', 'Bélanger, D', 'Dea, S', 'Bigras-Poulin, M']",,,,
,PMC,An episode of diarrhea in calves of a well-managed dairy herd.,,PMC1687215,,,,,"['Wright, A K', 'Giger, R', 'Arnold, T M', 'Janzen, E D']",,,,
,PMC,Feline immunodeficiency virus: an interesting model for AIDS studies and an important cat pathogen.,,PMC172850,,,"The lentivirus feline immunodeficiency virus (FIV) is a widespread pathogen of the domestic cat that is mainly transmitted through bites, although other means of transmission are also possible. Its prevalence ranges from 1 to 10% in different cat populations throughout the world, thus representing a large reservoir of naturally infected animals. FIV resembles the human immunodeficiency virus (HIV) in many respects. Similarities include the structural features of the virion, the general organization and great variability of the genome, the life cycle in the infected host, and most importantly, the pathogenic potential. Infection is associated with laboratory signs of immunosuppression as well as with a large variety of superinfections, tumors, and neurological manifestations. Our understanding of FIV is steadily improving and is providing important clues to the pathogenesis of immunodeficiency-inducing lentiviruses. The cellular receptor for FIV is different from the feline equivalent of the human CD4 molecule used by HIV; nevertheless, the major hallmark of infection is a progressive loss of CD4+ T lymphocytes as in HIV infection. The mechanisms by which FIV escapes the host's immune responses are being actively investigated. FIV causes lysis of infected T cells and also appears to predispose these cells to apoptosis. Infection of macrophages and other cell types has also been documented. For reasons yet to be understood, antibody-mediated neutralization of fresh FIV isolates is very inefficient both in vitro and in vivo. Vaccination studies have provided some encouraging results, but the difficulties encountered appear to match those met in HIV vaccine development. FIV susceptibility to antiviral agents is similar to that of HIV, thus providing a valuable system for in vivo preclinical evaluation of therapies. It is concluded that in many respects FIV is an ideal model for AIDS studies.",,"['Bendinelli, M', 'Pistello, M', 'Lombardi, S', 'Poli, A', 'Garzelli, C', 'Matteucci, D', 'Ceccherini-Nelli, L', 'Malvaldi, G', 'Tozzini, F']",,,,
,PMC,Abstracts: Part II,,PMC1382850,,,,,,,,,
,PMC,Disulfide bonds between two envelope proteins of lactate dehydrogenase-elevating virus are essential for viral infectivity.,,PMC188620,,,"Disulfide bonds were found to link the nonglycosylated envelope protein VP-2/M (19 kDa), encoded by open reading frame 6, and the major envelope glycoprotein VP-3 (25 to 42 kDa), encoded by open reading frame 5, of lactate dehydrogenase-elevating virus (LDV). The two proteins comigrated in a complex of 45 to 55 kDa when the virion proteins were electrophoresed under nonreducing conditions but dissociated under reducing conditions. Furthermore, VP-2/M was quantitatively precipitated along with VP-3 in this complex by three neutralizing monoclonal antibodies to VP-3. The infectivity of LDV was rapidly and irreversibly lost during incubation with 5 to 10 mM dithiothreitol (> 99% in 6 h at room temperature), which is known to reduce disulfide bonds. LDV inactivation correlated with dissociation of VP-2/M and VP-3. The results suggest that disulfide bonds between VP-2/M and VP-3 are important for LDV infectivity. Hydrophobic moment analyses of the predicted proteins suggest that VP-2/M and VP-3 both possess three adjacent transmembrane segments and only very short ectodomains (10 and 32 amino acids, respectively) with one and two cysteines, respectively. Inactivation of LDV by dithiothreitol and dissociation of the two envelope proteins were not associated with alterations in LDV's density or sedimentation coefficient.",,"['Faaberg, K S', 'Even, C', 'Palmer, G A', 'Plagemann, P G']",,,,
,PMC,Mouse hepatitis virus receptor activities of an MHVR/mph chimera and MHVR mutants lacking N-linked glycosylation of the N-terminal domain.,,PMC188607,,,"Mouse hepatitis virus binds to the N-terminal domain of its receptor, MHVR, a murine biliary glycoprotein with four immunoglobulin-like domains (G.S. Dveksler, M. N. Pensiero, C. W. Dieffenbach, C. B. Cardellichio, A.A. Basile, P.E. Elia, and K. V. Holmes, Proc. Natl. Acad. Sci. USA 90:1716-1720, 1993). A recombinant protein with only the anchored N-terminal domain was not a functional receptor, but a recombinant protein with the N-terminal domain of MHVR linked to the second and third immunoglobulin-like domains and anchor from the mouse poliovirus receptor homolog, mph, was a functional receptor for mouse hepatitis virus. The native four-domain MHVR has 16 potential N-linked glycosylation sites, including three on the N-terminal domain. Recombinant proteins lacking each one of these three sites or all three of them were functional receptors. Thus, glycosylation of the N-terminal domain is not required, but a glycoprotein longer than the N-terminal domain is required for virus receptor activity.",,"['Dveksler, G S', 'Basile, A A', 'Cardellichio, C B', 'Holmes, K V']",,,,
,PMC,Isolation of a monoclonal antibody which blocks vaccinia virus infection.,,PMC188602,,,"We have isolated a monoclonal antibody, B2, that neutralizes vaccinia virus infection. B2 reacts with a trypsin-sensitive cell surface epitope. B2 does not neutralize infection of herpes simplex virus, suggesting that the B2-reactive epitope is specifically involved in vaccinia virus entry. A survey of 12 different cell lines reveals a correlation between B2 reactivity and susceptibility to vaccinia virus infection. In addition, B2 interferes with vaccinia virus adsorption to target cells. Taken together, the B2-reactive epitope is part of a receptor that appears important for vaccinia virus entry.",,"['Chang, W', 'Hsiao, J C', 'Chung, C S', 'Bair, C H']",,,,
,PMC,The effect of two closely inserted transcription consensus sequences on coronavirus transcription.,,PMC188573,,,"Insertion of an intergenic region from the murine coronavirus mouse hepatitis virus into a mouse hepatitis virus defective interfering (DI) RNA led to transcription of subgenomic DI RNA in helper virus-infected cells. Using this system, we studied how two intergenic regions in close proximity affected subgenomic RNA synthesis. When two intergenic regions were separated by more than 100 nucleotides, slightly less of the larger subgenomic DI RNA (synthesized from the upstream intergenic region) was made; this difference was significant when the intergenic region separation was less than about 35 nucleotides. Deletion of sequences flanking the two intergenic regions inserted in close proximity did not affect transcription. No significant change in the ratio of the two subgenomic DI RNAs was observed when the sequence between the two intergenic regions was altered. Removal of the downstream intergenic region restored transcription of the larger subgenomic DI RNA. The UCUAAAC consensus sequence was needed for efficient suppression of the larger subgenomic DI RNA synthesis. These results demonstrated that the downstream intergenic sequence was suppressing subgenomic DI RNA synthesis from the upstream intergenic region. We discuss possible mechanisms to account for the regulation of this suppression of subgenomic DI RNA synthesis and the ways in which they relate to the general regulation of coronavirus transcription.",,"['Joo, M', 'Makino, S']",,,,
,PMC,Efficient system of homologous RNA recombination in brome mosaic virus: sequence and structure requirements and accuracy of crossovers.,,PMC188556,,,"Brome mosaic virus (BMV), a tripartite positive-stranded RNA virus of plants engineered to support intersegment RNA recombination, was used for the determination of sequence and structural requirements of homologous crossovers. A 60-nucleotide (nt) sequence, common between wild-type RNA2 and mutant RNA3, supported efficient repair (90%) of a modified 3' noncoding region in the RNA3 segment by homologous recombination with wild-type RNA2 3' noncoding sequences. Deletions within this sequence in RNA3 demonstrated that a nucleotide identity as short as 15 nt can support efficient homologous recombination events, while shorter (5-nt) sequence identity resulted in reduced recombination frequency (5%) within this region. Three or more mismatches within a downstream portion of the common 60-nt RNA3 sequence affected both the incidence of recombination and the distribution of crossover sites, suggesting that besides the length, the extent of sequence identity between two recombining BMV RNAs is an important factor in homologous recombination. Site-directed mutagenesis of the common sequence in RNA3 did not reveal a clear correlation between the stability of predicted secondary structures and recombination activity. This indicates that homologous recombination does not require similar secondary structures between two recombining RNAs at the sites of crossovers. Nearly 20% of homologous recombinants were imprecise (aberrant), containing either nucleotide mismatches, small deletions, or small insertions within the region of crossovers. This implies that homologous RNA recombination is not as accurate as proposed previously. Our results provide experimental evidence that the requirements and thus the mechanism of homologous recombination in BMV differ from those of previously described heteroduplex-mediated nonhomologous recombination (P. D. Nagy and J. J. Bujarski, Proc. Natl. Acad. Sci. USA 90:6390-6394, 1993).",,"['Nagy, P D', 'Bujarski, J J']",,,,
,PMC,Targeting of a heterodimeric membrane protein complex to the Golgi: rubella virus E2 glycoprotein contains a transmembrane Golgi retention signal.,,PMC275811,,,"Rubella virus (RV) envelope glycoproteins, E2 and E1, form a heterodimeric complex that is targeted to medial/trans-Golgi cisternae. To identify the Golgi targeting signal(s) for the E2/E1 spike complex, we constructed chimeric proteins consisting of domains from RV glycoproteins and vesicular stomatitis virus (VSV) G protein. The location of the chimeric proteins in stably transfected Chinese hamster ovary cells was determined by immunofluorescence, immunoelectron microscopy, and by the extent of processing of their N-linked glycans. A trans-dominant Golgi retention signal was identified within the C-terminal region of E2. When the transmembrane (TM) and cytoplasmic (CT) domains of VSV G were replaced with those of RV E2, the hybrid protein (G-E2TMCT+) was retained in the Golgi. Transport of G-E2TMCT+ to the Golgi was rapid (t1/2 = 10-20 min). The G-E2TMCT+ protein was determined to be distal to or within the medial Golgi based on acquisition of endo H resistance but proximal to the trans-Golgi network since it lacked sialic acid. Deletion analysis revealed that only the TM domain of E2 was required for Golgi targeting. Although the cytoplasmic domain of E2 was not necessary for Golgi retention, it was required for efficient transport of VSV G-RV chimeras out of the endoplasmic reticulum. When assayed in sucrose velocity sedimentations gradients, the Golgi-retained G-E2TMCT+ protein behaved as a dimer. Unlike virtually all other Golgi targeting signals, the E2 TM domain does not contain any polar amino acids. The TM and CT domains of E1 were not required for targeting of E2 and E1 to the Golgi indicating that a heterodimer of two integral membrane proteins can be retained in the Golgi by a single retention signal.",,"['Hobman, T C', 'Woodward, L', 'Farquhar, M G']",,,,
,PMC,Thymic epithelial defects and predisposition to autoimmune disease in BB rats.,,PMC1887500,,,"We report an association between thymic epithelial defects and predisposition to autoimmunity. Diabetes-prone (DP) BB rats develop spontaneous hyperglycemia and are deficient in T cell subsets expressing the RT6 alloantigen. Diabetes resistant (DR) BB rats become diabetic if depleted of RT6+ T cells. The inciting immune system defects are unknown. We made the following observations: 1) Regions of thymic cortex and medulla devoid of thymic epithelium exist in DP-BB, DR-BB, and Lewis rats, all of which are susceptible to autoimmune disorders. Such defects were absent in eight normal rat strains. 2) Thymic epithelial defects are absent at birth, but present in BB rats at 4 weeks of age. 3) The genetic predisposition to thymic epithelial defects is an autosomal dominant trait. 4) The observation of thymic defects in (DP x WF)F1 rats led to the prediction that such animals, which never develop spontaneous autoimmunity, might be susceptible to its induction. Following depletion of RT6+ T cells we observed diabetes in 91%, and thyroiditis in 43%, of treated F1 animals (n = 23). Pancreatic insulitis was uniformly present. Because thymic epithelium participates in the positive and negative selection of developing thymocytes, we propose that thymic epithelial defects may play an important role in the predisposition of BB rats to autoimmunity.",,"['Doukas, J.', 'Mordes, J. P.', 'Swymer, C.', 'Niedzwiecki, D.', 'Mason, R.', 'Rozing, J.', 'Rossini, A. A.', 'Greiner, D. L.']",,,,
,PMC,"Inhibition of human cytomegalovirus in culture by alkenyl guanine analogs of the thiazolo[4,5-d]pyrimidine ring system.",,PMC188302,,,"A series of alkyl and alkenyl guanine analogs containing a thiazolo[4,5-d]pyrimidine ring system were prepared by reaction of the appropriate alkyl halide with the sodium salt of the heterocycle. In preliminary antiviral efficacy evaluations against laboratory strains of both human cytomegalovirus (HCMV) and herpes simplex virus types 1 and 2, it was determined that two of the compounds (T70072 and T01132) were more active and less toxic in stationary-phase cell monolayers than were the other derivatives tested. T01132 and T70072, which have 2-pentenyl and 3-methyl-2-butenyl moieties attached to position 3 of the 5-aminothiazolo[4,5-d]pyrimidine-2,7-dione, respectively, were then more extensively evaluated for anti-HCMV activity. The concentrations of T01132 and T70072 required to inhibit HCMV by 50% in plaque reduction assays were approximately 0.5 and 6.8 microM, respectively. These two compounds inhibited the growth of KB, MRC-5, or Vero cells at concentrations of 75 to 150 microM, depending upon the cell line. In bone marrow progenitor cells T01132 was slightly less toxic than ganciclovir (DHPG). The 50% inhibitory concentrations of T01132 against clinical isolates and DHPG-resistant strains of HCMV were approximately the same as those obtained for laboratory strains of HCMV (approximately 0.5 microM). When tested in combination with DHPG, the resultant antiviral activity was determined to be additive but not synergistic. Experiments performed using variations of the viral multiplicity of infection (MOI) demonstrated that T01132 was more active than DHPG at a low MOI (0.002 or 0.02). However, when a higher MOI (0.2 or 2.0) was used, DHPG was more efficacious than T01132. In experiments in which drug was added at various times post-viral infection, T01132 was most effective when added within the first 24 h post-HCMV infection while DHPG was able to protect cells in this assay system when added up to 48 h postinfection, indicating that T01132 is exerting its antiviral effect on events leading up to and possibly including viral DNA synthesis. The data presented in this report suggest that the antiviral activity of alkenyl-substituted thiazolopyrimidine derivatives may represent a mechanism of action against herpesviruses alternative to that of classical nucleoside analogs such as acyclovir or DHPG.",,"['Lewis, A F', 'Drach, J C', 'Fennewald, S M', 'Huffman, J H', 'Ptak, R G', 'Sommadossi, J P', 'Revankar, G R', 'Rando, R F']",,,,
,PMC,Effect of template size on accumulation of defective interfering RNAs in protoplasts.,,PMC237324,,,"A turnip protoplast system has been used to study the effects of template size and sequence on the replication and/or stability of a small defective interfering (DI) RNA associated with turnip crinkle virus. Our results indicated that as little as a single base difference in the size of the molecule in some regions, rather than the specific sequence, affected the level of DI RNA accumulating in protoplasts.",,"['Zhang, C', 'Simon, A E']",,,,
,PMC,A cis-acting function for the coronavirus leader in defective interfering RNA replication.,,PMC237289,,,"To test the hypothesis that the 65-nucleotide (nt) leader on subgenomic mRNAs suffices as a 5'-terminal cis-acting signal for RNA replication, a corollary to the notion that coronavirus mRNAs behave as replicons, synthetic RNA transcripts of a cloned, reporter-containing N mRNA (mRNA 7) of the bovine coronavirus with a precise 5' terminus and a 3' poly(A) of 68 nt were tested for replication after being transfected into helper virus-infected cells. No replication was observed, but synthetic transcripts of a cloned reporter-containing defective interfering (DI) RNA differing from the N mRNA construct by 433 nt of continuous 5'-proximal genomic sequence between the leader and the N open reading frame did replicate and become packaged, indicating the insufficiency of the leader alone as a 5' signal for replication of transfected RNA molecules. The leader was shown to be a necessary part of the cis-acting signal for DI RNA replication, however, since removal of terminal bases that destroyed a predicted intraleader stem-loop also destroyed replicating ability. Surprisingly, when the same stem-loop was disrupted by base substitutions, replication appeared only minimally impaired and the leader was found to have rapidly reverted to wild type during DI RNA replication, a phenomenon reminiscent of high-frequency leader switching in the mouse hepatitis coronavirus. These results suggest that once a minimal structural requirement for leader is fulfilled for initiation of DI RNA replication, the wild-type leader is strongly preferred for subsequent replication. They also demonstrate that, in contrast to reported natural mouse hepatitis coronavirus DI RNAs, the DI RNA of the bovine coronavirus does not require sequence elements originating from discontinuous downstream regions within the polymerase gene for replication or for packaging.",,"['Chang, R Y', 'Hofmann, M A', 'Sethna, P B', 'Brian, D A']",,,,
,PMC,Genetics of mouse hepatitis virus transcription: evidence that subgenomic negative strands are functional templates.,,PMC237282,,,"Mouse hepatitis virus (MHV) A59 temperature-sensitive (ts) mutants belonging to complementation group C were characterized and mapped by standard genetic recombination techniques. Temperature shift experiments early in infection suggested that the group C allele can be divided into two phenotypically distinct subgroups, designated C1 and C2. Since previous data indicated that the group C1 mutants probably contained an early defect which affects negative-strand synthesis, RNA synthesis was further examined by analyzing replicative-form (RF) RNA. Full-length as well as subgenomic-length RF RNAs were radiolabeled from 3 to 12 h postinfection (p.i.) and labeled late in infection after shift to the nonpermissive temperature (39.5 degrees C). The relative percent molar ratios of each mRNA and corresponding RF RNA were roughly equivalent throughout infection. Temperature shift experiments at 5.5 or 6.0 h p.i. resulted in an 83 to 92% reduction in the amount of total RF RNA at 39.5 degrees C. Radiolabeling time course experiments after temperature shift to 39.5 degrees C also demonstrated incorporation (6 to 9 h p.i.) into both subgenomic-length and full-length RF RNAs, suggesting that previously transcribed negative strands were functional templates throughout infection. To determine if the reduction in RF RNA was due to a decrease in positive- or negative-strand RNA synthesis, rates of mRNA synthesis were calculated from both full-length and subgenomic-length templates. The rate of mRNA synthesis after the shift was increased at 39.5 degrees C compared with that at 32 degrees C regardless of the template used; however, transcription rates calculated from subgenomic-length templates were similar to those of other viral and eukaryotic polymerases. These findings support the notion that the group C1 allele regulates negative-strand RNA synthesis and strongly suggest that the subgenomic negative-strand RNAs are probably the predominant functional templates for the synthesis of positive-strand RNAs late in infection.",,"['Schaad, M C', 'Baric, R S']",,,,
,PMC,Identification of the cis-acting signal for minus-strand RNA synthesis of a murine coronavirus: implications for the role of minus-strand RNA in RNA replication and transcription.,,PMC237278,,,"Minus-strand RNA is the first RNA species made by plus-strand RNA viruses, such as mouse hepatitis virus (MHV), and serves as a template for subsequent RNA replication and transcription. The regulation of minus-strand RNA synthesis has been difficult to study because of the paucity of minus-strand RNA. We have optimized a ribonuclease (RNase) protection assay which enabled the detection of minus-strand RNA synthesis from nonreplicating RNAs, thus clearly separating minus-strand from plus-strand RNA synthesis. We used an MHV defective interfering (DI) RNA containing a chloramphenicol acetyltransferase gene as a reporter to determine the cis-acting signal for MHV minus-strand RNA synthesis. It was found that minus-strand RNAs existed in double-stranded RNA form in the cell. By using various deletion clones, we demonstrated that the cis-acting signal for minus-strand RNA synthesis resides in the 55 nucleotides from the 3' end plus poly(A) tail of the MHV genome. This is much shorter than the 436 nucleotides previously reported for the 3'-end replication signal. No specific upstream MHV sequence was required for the initiation of minus-strand RNA synthesis. This finding suggests that the requirement for minus-strand RNA synthesis is much less stringent than that for genomic and subgenomic plus-strand RNA synthesis and that some of the minus-strand RNAs made may not be functional since they may lack the recognition signals for RNA replication or transcription. We further showed that the DI clones which actively transcribed a subgenomic mRNA from an internal intergenic sequence synthesized much less minus-strand RNA than those clones which did not transcribe subgenomic mRNAs, indicating that minus-strand RNA synthesis was inhibited by transcription from an internal promoter of the same DI RNA. This result also suggests that the regulation of the quantities of subgenomic mRNAs is not at the point of minus-strand RNA synthesis but rather at plus-strand RNA synthesis. Furthermore, the finding that the leader sequence was not required for minus-strand RNA synthesis suggests that the leader RNA regulates mRNA transcription during plus-strand RNA synthesis.",,"['Lin, Y J', 'Liao, C L', 'Lai, M M']",,,,
,PMC,Major receptor-binding and neutralization determinants are located within the same domain of the transmissible gastroenteritis virus (coronavirus) spike protein.,,PMC237264,,,"The spike glycoprotein (S) of coronavirus, the major target for virus-neutralizing antibodies, is assumed to mediate the attachment of virions to the host cell. A 26-kilodalton fragment proteolytically cleaved from transmissible gastroenteritis virus (TGEV) S protein was previously shown to bear two adjacent antigenic sites, A and B, both defined by high-titer neutralizing antibodies. Recombinant baculoviruses expressing C-terminal truncations of the 26-kilodalton region were used to localize functionally important determinants in the S protein primary structure. Two overlapping 223- and 150-amino-acid-long products with serine 506 as a common N terminus expressed all of the site A and B epitopes and induced virus-binding antibodies. Coexpression of one of these truncated protein S derivatives with aminopeptidase N (APN), a cell surface molecule acting as a receptor for TGEV, led to the formation of a complex which could be immunoprecipitated by anti-S antibodies. These data provide evidence that major neutralization-mediating and receptor-binding determinants reside together within a domain of the S protein which behaves like an independent module. In spite of their ability to prevent S-APN interaction, the neutralizing antibodies appeared to recognize a preformed complex, thus indicating that antibody- and receptor-binding determinants should be essentially distinct. Together these findings bring new insight into the molecular mechanism of TGEV neutralization.",,"['Godet, M', 'Grosclaude, J', 'Delmas, B', 'Laude, H']",,,,
,PMC,Entry and release of transmissible gastroenteritis coronavirus are restricted to apical surfaces of polarized epithelial cells.,,PMC237259,,,"The transmissible gastroenteritis coronavirus (TGEV) infects the epithelial cells of the intestinal tract of pigs, resulting in a high mortality rate in piglets. This study shows the interaction of TGEV with a porcine epithelial cell line. To determine the site of viral entry, LLC-PK1 cells were grown on permeable filter supports and infected with TGEV from the apical or basolateral side. Initially after plating, the virus was found to enter the cells from both sides. During further development of cell polarity, however, the entry became restricted to the apical membrane. Viral entry could be blocked by a monoclonal antibody to the viral receptor aminopeptidase N. Confocal laser scanning microscopy showed that this receptor protein was present at both the apical and basolateral plasma membrane domains just after plating of the cells but that it became restricted to the apical plasma membrane during culture. To establish the site of viral release, the viral content of the apical and basolateral media of apically infected LLC-PK1 cells was measured by determining the amount of radioactively labelled viral proteins and infectious viral particles. We found that TGEV was preferentially released from the apical plasma membrane. This conclusion was confirmed by electron microscopy, which demonstrated that newly synthesized viral particles attached to the apical membrane. The results support the idea that the rapid lateral spread of TGEV infection over the intestinal epithelia occurs by the preferential release of virus from infected epithelial cells into the gut lumen followed by efficient infection of nearby cells through the apical domain.",,"['Rossen, J W', 'Bekker, C P', 'Voorhout, W F', 'Strous, G J', 'van der Ende, A', 'Rottier, P J']",,,,
,PMC,Special peptidyl-tRNA molecules can promote translational frameshifting without slippage.,,PMC359349,,,"Recently we described an unusual programmed +1 frameshift event in yeast retrotransposon Ty3. Frameshifting depends on the presence of peptidyl-tRNA(AlaCGC) on the GCG codon in the ribosomal P site and on a translational pause stimulated by the slowly decoded AGU codon. Frameshifting occurs on the sequence GCG-AGU-U by out-of-frame binding of a valyl-tRNA to GUU without slippage of peptidyl-tRNA(AlaCGC). This mechanism challenges the conventional understanding that frameshift efficiency must correlate with the ability of mRNA-bound tRNA to slip between cognate or near-cognate codons. Though frameshifting does not require slippery tRNAs, it does require special peptidyl-tRNAs. We show that overproducing a second isoacceptor whose anticodon had been changed to CGC eliminated frameshifting; peptidyl-tRNA(AlaCGC) must have a special capacity to induce +1 frameshifting in the adjacent ribosomal A site. In order to identify other special peptidyl-tRNAs, we tested the ability of each of the other 63 codons to replace GCG in the P site. We found no correlation between the ability to stimulate +1 frameshifting and the ability of the cognate tRNA to slip on the mRNA--several codons predicted to slip efficiently do not stimulate frameshifting, while several predicted not to slip do stimulate frameshifting. By inducing a severe translational pause, we identified eight tRNAs capable of inducing measurable +1 frameshifting, only four of which are predicted to slip on the mRNA. We conclude that in Saccharomyces cerevisiae, special peptidyl-tRNAs can induce frameshifting dependent on some characteristic(s) other than the ability to slip on the mRNA.",,"['Vimaladithan, A', 'Farabaugh, P J']",,,,
,PMC,Rotavirus-specific intestinal immune response in mice assessed by enzyme-linked immunospot assay and intestinal fragment culture.,,PMC368401,,,"Primate rotavirus strain RRV and bovine strain WC3 or reassortants made between these animal viruses and human rotaviruses have been administered to infants as candidate vaccines. We compared RRV and WC3 in a murine model of oral infection. We determined the relative capacities of these viruses to induce a virus-specific humoral immune response by intestinal lymphocytes as tested by enzyme-linked immunospot assay, intestinal fragment culture, and enzyme-linked immunosorbent assay of intestinal contents. We found that inoculation of mice with RRV induced higher frequencies of virus-specific immunoglobulin A (IgA)-secreting cells in the lamina propria, greater quantities of virus-specific IgA in intestinal fragment cultures, and greater quantities of virus-specific IgA in intestinal secretions than did inoculation with WC3 or inactivated RRV (iRRV). The induction of an IgA response in serum was predictive of an IgA response among intestinal lymphocytes after inoculation with RRV but not WC3. In addition, large quantities of IgG, IgA, and IgM not specific for rotavirus were produced in fragment cultures from mice inoculated with RRV but not in cultures from mice inoculated with WC3 or iRRV. Possible mechanisms of RRV-induced polyclonal stimulation of intestinal B cells are discussed.",,"['Khoury, C A', 'Brown, K A', 'Kim, J E', 'Offit, P A']",,,,
,PMC,A Th1 cell line (3E9.1) from resistant A/J mice inhibits induction of macrophage procoagulant activity in vitro and protects against MHV-3 mortality in vivo.,,PMC1415033,,,"Induction of immune coagulants has been implicated in the pathogenesis of murine hepatitis virus strain 3 (MHV-3)-induced fulminant hepatic necrosis. Previous work from our laboratory has shown that the induction of procoagulant activity (PCA) correlates with the resistance/susceptibility to disease in inbred and recombinant inbred (RI) strains of mice. Macrophages from susceptible, but not resistant, strains of mice expressed increased levels of PCA in response to MHV-3 stimulation. T lymphocytes, however, had a marked regulatory role in the final expression of macrophage PCA. CD3+ CD4+ CD8- lymphocytes from RI H-2 compatible susceptible mice were able to instruct macrophages from susceptible mice to express significantly augmented levels of PCA, whereas CD3+ lymphocytes from RI H-2 compatible MHV-3-immunized resistant mice were able to suppress induction of PCA. In this present study, T-cell lines were derived from draining popliteal lymph nodes from resistant A/J mice, which had been immunized with MHV-3. All T-cell lines showed marked proliferation to MHV-3 and MHV-JHM which was major histocompatibility complex (MHC) restricted. All cell lines were CD3+, four of these were CD4+ and one was CD8+. All of the CD4+ cell lines produced IL-2 and two produced interferon-gamma (IFN-gamma), consistent with the Th1 cytokine profile. One cell line (3E9.1) was able to inhibit the induction of macrophage PCA through production of a soluble factor although cell-to-cell contact could not be excluded. This CD4+ T-cell line conferred protection to infected and susceptible AXB8 mice. These results demonstrate that the existence of a Th1 subpopulation of cells with a regulatory effect on macrophage PCA induction in MHV-3-infected mice contributes to the resistance of the A/J strain of mice to MHV-3 infection.",,"['Chung, S', 'Gorczynski, R', 'Cruz, B', 'Fingerote, R', 'Skamene, E', 'Perlman, S', 'Leibowitz, J', 'Fung, L', 'Flowers, M', 'Levy, G']",,,,
,PMC,The impact of the intracerebral antibody response on the clinical course of a virus-induced demyelination in a rat model system.,,PMC1016717,,,,,"['Dörries, R', 'Imrich, H', 'Hein, A', 'Czub, S', 'Schwender, S']",,,,
,PMC,Apoptosis induced in mouse hepatitis virus-infected cells by a virus-specific CD8+ cytotoxic T-lymphocyte clone.,,PMC237198,,,"Morphological changes of mouse hepatitis virus-infected J774.1 cells cocultured with cloned mouse hepatitis virus-specific CD8+ cytotoxic T lymphocytes were examined by electron microscopy. Condensation and margination of chromatin, cellular shrinkage with severe vacuolar degeneration, and blebbing were observed. In addition, fragmentation of cellular DNA was observed, and a decrease in virus titer was accompanied by those changes. These findings show that the cloned cytotoxic T lymphocytes induce in the target cell an internal degradation program termed apoptosis, which results in virus clearance.",,"['Shibata, S', 'Kyuwa, S', 'Lee, S K', 'Toyoda, Y', 'Goto, N']",,,,
,PMC,Map locations of mouse hepatitis virus temperature-sensitive mutants: confirmation of variable rates of recombination.,,PMC237188,,,"Using standard genetic recombination techniques, studies in our laboratory suggest that recombination rates are very high and vary in different portions of the mouse hepatitis virus (MHV) genome. To determine the actual recombination frequencies in the MHV genome and localize the nucleotide boundaries of individual viral genes, we have sequenced temperature-sensitive and revertant viruses to identify the location of specific mutant alleles. Complementation group F RNA+ ts mutants (LA7, NC6, and NC16) each contained a unique mutation which was tightly linked to the ts phenotype and resulted in a conservative or nonconservative amino acid change in the MHV S glycoprotein gene. In agreement with previous recombination mapping studies, the mutation in LA7 and NC6 mapped within the S1 domain while NC16 mapped within the S2 domain. To determine the map coordinates of the MHV polymerase genes, several RNA- mutants and their revertants belonging to complementation groups C (NC3 and LA9) and E (LA18 and NC4) were also sequenced. Mutations were identified in each virus that were tightly linked to the ts phenotype and resulted in either a conservative or nonconservative amino acid change. The group C allele spanned the ORF 1a/ORF 1b junction, while the group E mutants mapped at the C terminus of ORF 1b about 20 to 22 kb from the 5' end of the genome. Mutation rates, calculated from the reversion frequencies of plaque-purified ts viruses requiring a single nucleotide alteration for reversion, approached 1.32 (+/- 0.89) x 10(-4) substitutions per nucleotide site per round of template copying. Detailed recombination mapping studies across known distances between these different ts alleles has confirmed that homologous recombination rates approached 25% and varied within different portions of the MHV genome.",,"['Fu, K', 'Baric, R S']",,,,
,PMC,Expression of alpha/beta interferons (IFN-alpha/beta) and their relationship to IFN-alpha/beta-induced genes in lymphocytic choriomeningitis.,,PMC237178,,,"Expression of alpha interferon (IFN-alpha)-, IFN-beta-, and IFN-alpha/beta-induced genes was monitored during the development of lymphocytic choriomeningitis (LCM) to assess whether a restricted influence of these antiviral cytokines could be found in the central nervous system (CNS). High levels of IFN-alpha (83 +/- 42 U/ml) were present in the blood of LCM virus-infected mice 3 days postinfection, whereas IFN-beta was not detected (< 1.0 U/ml) at any time point. Spleens contained high levels of IFN-alpha and IFN-beta mRNAs at days 1 and 3 postinfection, whereas no IFN-alpha mRNA and only low levels of IFN-beta mRNA were detected in brains. In situ hybridization showed IFN-alpha mRNA-expressing cells in the marginal zones of the spleen and in the subcapsular sinus and outer cortex of cervical lymph nodes. The expression of 2',5'-oligoadenylate synthetase (2',5'-OAS) mRNA followed the expression of IFN-beta mRNA in the brain, whereas 2',5'-OAS mRNA in the periphery was associated with systemic IFN-alpha. The localization of IFN-alpha-expressing cells in the spleen and lymph nodes in proximity to T- and B-cell compartments is consistent with a role for these cytokines in immune regulation. Furthermore, the absence of IFN-alpha and the relatively low level and delayed expression of IFN-beta in the brain suggest that the CNS is an especially vulnerable organ for virus replication. With certain strains of LCM virus, the absence of early antiviral IFN-alpha/beta activity and preferential virus growth in the brain might lead to targeted T-cell inflammation of the CNS, resulting in death of the animal.",,"['Sandberg, K', 'Eloranta, M L', 'Campbell, I L']",,,,
,PMC,Evidence for a putative second receptor for porcine transmissible gastroenteritis virus on the villous enterocytes of newborn pigs.,,PMC237165,,,"Aminopeptidase-N (APN) has been identified [B. Delmas, J. Gelfi, R. L'Haridon, L. K. Vogel, H. Sjostrom, O. Noren, and H. Laude, Nature (London) 357:417-420, 1992] as a major receptor for porcine transmissible gastroenteritis virus (TGEV). Binding of TGEV to villous enterocytes from the jejuna of newborn pigs is saturable and at a higher level than that of binding of virus to newborn cryptal enterocytes or to enterocytes from older piglets (H. M. Weingartl and J. B. Derbyshire, Vet. Microbiol. 35:23-32, 1993). The distribution of APN in enterocytes in the jejuna of neonatal and 3 week-old-piglets, as determined by the measurement of enzymatic activity and by labeling of the cells with an anti-APN monoclonal antibody, did not correspond with the reported distribution of saturable binding sites on enterocytes. Monoclonal antibodies, which were prepared against plasma membranes derived from enterocytes harvested from the upper villi of newborn pigs, blocked the replication of TGEV, but not the porcine respiratory coronavirus, in ST cells and immunoprecipitated a 200-kDa protein in ST cell lysates. This protein was demonstrated by immunohistochemistry and by fluorescence-activated cell scanning to be present on the villous enterocytes of newborn pigs but to be lacking on the cryptal enterocytes of newborn pigs and on the villous and cryptal enterocytes of 3-week-old piglets. Since this distribution of the protein corresponds to the previously demonstrated distribution of saturable binding sites, we conclude that the 200-kDa protein may be an additional receptor for TGEV which is restricted to the villous enterocytes of newborn pigs and which contributes to the age sensitivity of these animals to the virus.",,"['Weingartl, H M', 'Derbyshire, J B']",,,,
,PMC,Regulation of susceptibility and cell surface receptor for the B-lymphotropic papovavirus by N glycosylation.,,PMC237129,,,"The host range of the B-lymphotropic papovavirus (LPV) in cultured human cells is limited to a few B-lymphoma-derived cell lines. The constitutively expressed cell surface receptor for the virus is a major determinant restricting the LPV host range (G. Haun, O. T. Keppler, C. T. Bock, M. Herrmann, H. Zentgraf, and M. Pawlita, J. Virol. 67:7482-7492, 1993). Here we show that human B-lymphoma cells with low-level susceptibility are rendered highly susceptible to LPV infection by pretreatment with the N glycosylation inhibitor tunicamycin but remain nonsusceptible to infection by the related polyomavirus simian virus 40. Among the selective N glycosylation processing inhibitors, deoxymannojirimycin, but not deoxynojirimycin, swainsonine, or castanospermine, could mimic the effect of tunicamycin. Tunicamycin treatment also induced a drastic enhancement of the cells' LPV-binding capacity, indicating that the induction of LPV susceptibility might be mediated by an increase in the number of functional cell surface receptors and/or by increased receptor affinity. Sialidase sensitivity of the tunicamycin-induced LPV receptor showed that oligosaccharides carrying terminal sialic acids are necessary for binding and are likely to be O linked. The constitutive LPV receptor is also sialic acid dependent, which points to a possible identity with the sialic acid-dependent tunicamycin-induced LPV receptor. We conclude that removal or modification of certain N-linked oligosaccharides in human B-lymphoma cells can enhance expression or functional activity of the sialylated LPV receptor.",,"['Keppler, O T', 'Herrmann, M', 'Oppenländer, M', 'Meschede, W', 'Pawlita, M']",,,,
,PMC,"Characterization of a Borna disease virus glycoprotein, gp18.",,PMC237127,,,"Borna disease virus is a nonsegmented negative-strand RNA virus that causes neurologic disease in a wide variety of animal hosts. Here we describe identification and characterization of the first glycoprotein in this viral system. The 18-kDa glycoprotein, gp18, has been purified from infected rat brain. Isolation and microsequencing of this protein allowed identification of a 16.2-kDa open reading frame in the viral antigenome. Lectin binding and endoglycosidase sensitivity assays indicate that gp18 is an unusual N-linked glycoprotein.",,"['Kliche, S', 'Briese, T', 'Henschen, A H', 'Stitz, L', 'Lipkin, W I']",,,,
,PMC,Persistence of porcine reproductive and respiratory syndrome virus infection in a swine operation.,,PMC1263716,,,"A herd of Quebec seedstock pigs experienced in early 1992 a typical outbreak of porcine reproductive and respiratory syndrome (PRRS) associated with lesions of interstitial, proliferative and necrotizing pneumonia in weaned piglets. The nature of the infection was confirmed by serology using indirect immunofluorescence (IIF) and virus isolation in primary cultures of porcine alveolar macrophages (PAM). Farm production recovered after eight weeks of losses. In order to evaluate the persistence of infection in the herd, five SPF-piglets were introduced in two different sections of the PRRS-affected barn four months after the disappearance of clinical symptoms, and two others were placed in a neighboring building with apparently healthy farrow-to-finnish pigs. Clinical signs, body temperature, humoral immune response, virological and histopathological findings were recorded over a 42-day period. Clinical signs were evident in all of the sentinels and prolonged fever (> or = 40 degrees C) was recorded one day post-exposure (PE). Antibody titers to PRRS virus could be detected by IIF on PAM seven days PE, and reached 1:1024 by day 21 PE. Three of the sentinels developed significant virus neutralizing antibody titers (> 1:8 to < or = 1:128) by day 35 PE. In all cases, the virus could be isolated from the serum between day 7 and 42 PE. Thus, the virus and specific antibodies coexisted for several weeks. Lesions of interstitial pneumonia was demonstrated in few animals. In experimental inoculation studies, the viral strain isolated from the sentinel pigs produced severe reproductive disorders in two sows inoculated at 95 days of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)",,"['Bilodeau, R', 'Archambault, D', 'Vézina, S A', 'Sauvageau, R', 'Fournier, M', 'Dea, S']",,,,
,PMC,VETERINARY MEDICAL ETHICS,,PMC1686798,,,,,,,,,
,PMC,Equine rotaviruses with G14 serotype specificity circulate among venezuelan horses.,,PMC264117,,,Two group A rotavirus strains isolated from diarrheic foals in Venezuela were classified as belonging to G14 serotype by cross-neutralization tests and on the basis of the homology of the sequenced VP7 gene. This report confirms that rotavirus strains of G14 serotype specificity circulate among equine populations.,,"['Ciarlet, M', 'Reggeti, F', 'Piña, C I', 'Liprandi, F']",,,,
,PMC,Development and application of an enzyme immunoassay for coronavirus OC43 antibody in acute respiratory illness.,,PMC264068,,,"Study of coronavirus OC43 infections has been limited because of the lack of sensitive cell culture systems and serologic assays. To improve this circumstance, we developed an indirect enzyme immunoassay (EIA) to detect serum antibody to OC43. Antigen (100 ng) prepared by polyethylene glycol precipitation provided optimal results without a postcoat procedure. Evaluation of intraplate variation indicated that a > or = 2.5-fold increase in serum titer was significant. Sixteen of 18 (89%) paired serum samples with previously identified, reproducible increases in the level of hemagglutination inhibition (HAI) antibody to OC43 also showed significant increases as detected by EIA. Specificity for the EIA was established with paired sera obtained from persons given influenza immunizations or experiencing a respiratory infection. No rise in antibody titers occurred among 33 persons with documented coronavirus 229E infection. EIA was then performed on each of 419 paired serum samples from ambulatory chronic obstructive pulmonary disease patients and healthy older adults, from asthmatic adults presenting for emergency room treatment, and from persons hospitalized with acute respiratory symptoms. Twenty-three antibody rises to OC43 were detected; only nine of these were detected by the HAI test, and the HAI test did not detect any increases in antibody titers that were not detected by EIA. Nineteen of 25 coronavirus OC43 infections for which a month of infection could be assigned occurred between November and February. Overall, 4.4% of acute respiratory illnesses in the studied populations were associated with a coronavirus OC43 infection.",,"['Gill, E P', 'Dominguez, E A', 'Greenberg, S B', 'Atmar, R L', 'Hogue, B G', 'Baxter, B D', 'Couch, R B']",,,,
,PMC,Modulation of cellular macromolecular synthesis by coronavirus: implication for pathogenesis.,,PMC237110,,,"Infection with the murine coronavirus strain JHM decreases cell surface expression of major histocompatibility complex class I antigens. Northern blots showed that JHM virus infection rapidly reduced the level of actin mRNA, whereas the levels of major histocompatibility complex class I and tubulin mRNAs were reduced only slightly. By contrast, the mRNA levels of interleukin 1 beta, colony-stimulating factor 1 receptor, and tumor necrosis factor alpha increased following infection.",,"['Kyuwa, S', 'Cohen, M', 'Nelson, G', 'Tahara, S M', 'Stohlman, S A']",,,,
,PMC,Recombinant rabbit hemorrhagic disease virus capsid protein expressed in baculovirus self-assembles into viruslike particles and induces protection.,,PMC237106,,,"VP60, the unique component of rabbit hemorrhagic disease virus capsid, was expressed in the baculovirus system. The recombinant VP60, released in the supernatant of infected insect cells, assembled without the need of any other viral component to form viruslike particles (VLPs), structurally and immunologically indistinguishable from the rabbit hemorrhagic disease virion. Intramuscular vaccination of rabbits with the VLPs conferred complete protection in 15 days; this protection was found to be effective from the fifth day after VLP injection and was accompanied by a strong humoral response.",,"['Laurent, S', 'Vautherot, J F', 'Madelaine, M F', 'Le Gall, G', 'Rasschaert, D']",,,,
,PMC,Unusual heterogeneity of leader-mRNA fusion in a murine coronavirus: implications for the mechanism of RNA transcription and recombination.,,PMC237083,,,"Coronavirus mRNA transcription was thought to be regulated by the interaction between the leader RNA and the intergenic sequence (IS), probably involving direct RNA-RNA interactions between complementary sequences. In this study, we found that a particular strain of mouse hepatitis virus, JHM2c, which has a deletion of a 9-nucleotide (nt) sequence (UUUAUAAAC) immediately downstream of the leader RNA, transcribed subgenomic mRNA species containing a whole array of heterogeneous leader fusion sites. Using a transfected defective interfering RNA which contains an IS and a reporter (chloramphenicol acetyltransferase) gene and JHM2c as a helper virus, we demonstrated that subgenomic mRNAs transcribed from the defective interfering RNAs were extremely heterogeneous. The leader-mRNA fusion sites in this virus can be grouped into five types. In type I, the leader is fused with the consensus IS of the template RNA at a site within the UCUAA repeats, consistent with the classical model of discontinuous transcription. In type II, the leader is fused with the consensus IS as in type I, but the leader of mRNA contains some nucleotide substitutions within the UCUAA repeats. In type III, the leader is fused with mRNAs at a site either upstream or downstream of the consensus IS. The sequences around the fusion sites bear little or no homology to the leader. As a result, mRNAs contain sequences complementary to the template sequences upstream of the IS or have sequence deletions downstream of the IS. In type IV, the leader is fused to the IS at the 9-nt sequence immediately downstream of the UCUAA repeats. In type V, the leader-mRNA fusion site contains a duplication of a portion of the leader sequence or an insertion of nontemplated sequences which are not present in either leader or template RNA. These patterns of leader-mRNA fusion resemble the aberrant homologous recombination frequently seen in other RNA viruses. The degree of heterogeneity of leader fusion sites is dependent on the sequences of both the leader RNA and IS. These results suggest that leader-mRNA fusion in coronavirus transcription does not require direct RNA-RNA interaction between complementary sequences. A modified model of RNA transcription and recombination based on protein-RNA and protein-protein interactions is proposed. This study also provides a paradigm for aberrant homologous recombination.",,"['Zhang, X', 'Lai, M M']",,,,
,PMC,Coronavirus M proteins accumulate in the Golgi complex beyond the site of virion budding.,,PMC237073,,,"The prevailing hypothesis is that the intracellular site of budding of coronaviruses is determined by the localization of its membrane protein M (previously called E1). We tested this by analyzing the site of budding of four different coronaviruses in relation to the intracellular localization of their M proteins. Mouse hepatitis virus (MHV) and infectious bronchitis virus (IBV) grown in Sac(-) cells, and feline infectious peritonitis virus (FIPV) and transmissible gastroenteritis virus (TGEV) grown in CrFK cells, all budded exclusively into smooth-walled, tubulovesicular membranes located intermediately between the rough endoplasmic reticulum and Golgi complex, identical to the so-called budding compartment previously identified for MHV. Indirect immunofluorescence staining of the infected cells showed that all four M proteins accumulated in a perinuclear region. Immunogold microscopy localized MHV M and IBV M in the budding compartment; in addition, a dense labeling in the Golgi complex occurred, MHV M predominantly in trans-Golgi cisternae and trans-Golgi reticulum and IBV M mainly in the cis and medial Golgi cisternae. The corresponding M proteins of the four viruses, when independently expressed in a recombinant vaccinia virus system, also accumulated in the perinuclear area. Quantitative pulse-chase analysis of metabolically labeled cells showed that in each case the majority of the M glycoproteins carried oligosaccharide side chains with Golgi-specific modifications within 4 h after synthesis. Immunoelectron microscopy localized recombinant MHV M and IBV M to the same membranes as the respective proteins in coronavirus-infected cells, with the same cis-trans distribution over the Golgi complex. Our results demonstrate that some of the M proteins of the four viruses are transported beyond the budding compartment and are differentially retained by intrinsic retention signals; in addition to M, other viral and/or cellular factors are probably required to determine the site of budding.",,"['Klumperman, J', 'Locker, J K', 'Meijer, A', 'Horzinek, M C', 'Geuze, H J', 'Rottier, P J']",,,,
,PMC,Binding of measles virus to membrane cofactor protein (CD46): importance of disulfide bonds and N-glycans for the receptor function.,,PMC237050,,,"Two cellular proteins, membrane cofactor protein (MCP) and moesin, were reported recently to be functionally associated with the initiation of a measles virus infection. We have analyzed the interaction of measles virus with cell surface proteins, using an overlay binding assay with cellular proteins immobilized on nitrocellulose. Among surface-biotinylated proteins from a human rectal tumor cell line (HRT), measles virus was able to bind only to a 67-kDa protein that was identified as MCP. The virus recognized different isoforms of MCP expressed from human (HRT and HeLa) and simian (Vero) cell lines. The binding of measles virus to MCP was abolished after cleavage of the disulfide bonds by reducing agents as well as after enzymatic release of N-linked oligosaccharides. By contrast, removal of sialic acid or O-linked oligosaccharides did not affect the recognition of MCP measles virus. These data indicate that the receptor determinant of MCP is dependent on a conformation of the protein that is maintained by disulfide bonds and N-glycans present in the complement binding domains. Our results are consistent with a role of MCP as primary attachment site for measles virus in the initial stage of an infection. The functional relationship between MCP and moesin in a measles virus infection is discussed.",,"['Maisner, A', 'Schneider-Schaulies, J', 'Liszewski, M K', 'Atkinson, J P', 'Herrler, G']",,,,
,PMC,Peripheral blood mononuclear phagocytes mediate dissemination of murine cytomegalovirus.,,PMC237044,,,"Cytomegalovirus is transmitted with blood and organs from seropositive individuals, although the particular leukocyte population harboring latent or persistent virus remains poorly characterized. Murine cytomegalovirus, tagged with the Escherichia coli lacZ gene, was used to identify cells in which virus replicates during acute infection of immunocompetent mice. Recombinant murine cytomegaloviruses, RM461, RM460, and RM427, were constructed to express beta-galactosidase under control of the human cytomegalovirus ie1/ie2 promoter/enhancer. The lacZ gene was inserted between the ie2 and sgg1 genes in RM461 and RM460, disrupting a 0.85-kb late transcript that was found to be dispensable for replication in cultured cells as well as for infection of mice. In BALB/c mice, lacZ-tagged and wild-type viruses exhibited a similar 50% lethal dose and all had the capacity to latently infect the spleen. Peripheral blood mononuclear phagocytes were the major infected leukocyte cell type, as demonstrated by the ability of infected cells to adhere to glass and to phagocytize latex beads; however, these cells did not exhibit typical monocyte markers. Plaque assay for virus and 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining of frozen sections of organs from infected mice revealed that the major target organs included the spleen, adrenal glands, liver, and salivary glands, although tissues as diverse as brown fat and lungs were also involved. Individual blue-staining cells were readily identified in all infected tissues. These studies identified a mononuclear phagocyte, possibly a macrophage or dendritic cell precursor, as the vehicle of virus dissemination during acute infection, and demonstrate the utility of using lacZ-tagged murine cytomegalovirus for tropism, pathogenesis, and latency studies.",,"['Stoddart, C A', 'Cardin, R D', 'Boname, J M', 'Manning, W C', 'Abenes, G B', 'Mocarski, E S']",,,,
,PMC,Viral cell recognition and entry.,,PMC2142612,,,"Rhinovirus infection is initiated by the recognition of a specific cell-surface receptor. The major group of rhinovirus serotypes attach to intercellular adhesion molecule-1 (ICAM-1). The attachment process initiates a series of conformational changes resulting in the loss of genomic RNA from the virion. X-ray crystallography and sequence comparisons suggested that a deep crevice or canyon is the site on the virus recognized by the cellular receptor molecule. This has now been verified by electron microscopy of human rhinovirus 14 (HRV14) and HRV16 complexed with a soluble component of ICAM-1. A hydrophobic pocket underneath the canyon is the site of binding of various hydrophobic drug compounds that can inhibit attachment and uncoating. This pocket is also associated with an unidentified, possibly cellular in origin, ""pocket factor."" The pocket factor binding site overlaps the binding site of the receptor. It is suggested that competition between the pocket factor and receptor regulates the conformational changes required for the initiation of the entry of the genomic RNA into the cell.",,"Rossmann, M. G.",,,,
,PMC,The nucleic acid-binding zinc finger protein of potato virus M is translated by internal initiation as well as by ribosomal frameshifting involving a shifty stop codon and a novel mechanism of P-site slippage.,,PMC308388,,,"The genes for the capsid protein CP and the nucleic acid-binding 12K protein (pr12) of potato virus M (PVM) constitute the 3' terminal gene cluster of the PVM RNA genome. Both proteins are presumably translated from a single subgenomic RNA. We have identified two translational strategies operating in pr12 gene expression. Internal initiation at the first and the second AUG codon of the pr12 coding sequence results in the synthesis of the 12K protein. In addition the protein is produced as a CP/12K transframe protein by ribosomal frameshifting. For these studies parts of the CP and pr12 coding sequences including the putative frameshift region were introduced into an internal position of the beta-glucuronidase gene. Mutational analyses in conjunction with in vitro translation experiments identified a homopolymeric string of four adenosine nucleotides which together with a 3' flanking UGA stop codon were required for efficient frameshifting. The signal AAAAUGA is the first frameshift signal with a shifty stop codon to be analyzed in the eukaryotic system. Substitution of the four consecutive adenosine nucleotides by UUUU increased the efficiency of frameshifting, while substitution by GGGG or CCCC dramatically reduced the synthesis of the transframe protein. Also, UAA and UAG could replace the opal stop codon without effect on the frameshifting event, but mutation of UGA to the sense codon UGG inhibited transframe protein formation. These findings suggest that the mechanism of ribosomal frameshifting at the PVM signal is different from the one described by the 'simultaneous slippage' model in that only the string of four adenosine nucleotides represents the slippery sequence involved in a -1 P-site slippage.",,"['Gramstat, A', 'Prüfer, D', 'Rohde, W']",,,,
,PMC,Genetic control of bacterial suicide: regulation of the induction of PBSX in Bacillus subtilis.,,PMC196787,,,"PBSX is a phage-like bacteriocin (phibacin) of Bacillus subtilis 168. Bacteria carrying the PBSX genome are induced by DNA-damaging agents to lyse and produce PBSX particles. The particles cannot propagate the PBSX genome. The particles produced by this suicidal response kill strains nonlysogenic for PBSX. A 5.2-kb region which controls the induction of PBSX has been sequenced. The genes identified include the previously identified repressor gene xre and a positive control factor gene, pcf. Pcf is similar to known sigma factors and acts at the late promoter PL, which has been located distal to pcf. The first two genes expressed from the late promoter show homology to genes encoding the subunits of phage terminases.",,"['McDonnell, G E', 'Wood, H', 'Devine, K M', 'McConnell, D J']",,,,
,PMC,Development of nested PCR assays for detection of bovine respiratory syncytial virus in clinical samples.,,PMC263972,,,"Two nested PCR assays were developed for the detection of bovine respiratory syncytial virus (BRSV). Primers were selected from the gene encoding the F fusion protein (PCR-F) and the gene encoding the G attachment protein (PCR-G). Biotinylated oligonucleotide probes, termed F and G, were selected for the hybridization of the respective PCR products. The sensitivities of the PCR-F and PCR-G assays were similar, both detecting 0.1 tissue culture infective dose of the virus. The PCR-F assay amplified all bovine strains and one human strain (RS32) tested. No cross-reactions were observed with nine heterologous respiratory viruses. PCR-F products of bovine and human RSV strains were discriminated by using endonuclease restriction enzyme ScaI, which specifically cleaved, products of BRSV. Oligonucleotide probe F was also specific for products of BRSV. The PCR-G assay detected all bovine strains and none of the human strains tested. A faint electrophoretic band was also observed with products of Sendai virus. However, probe G did not hybridize with this product, only with products of BRSV. Nasal swabs collected from cattle with no symptoms and cattle in the acute stage of respiratory disease were analyzed for BRSV by the immunofluorescence (IF) method and by the PCR-F and PCR-G assays. The virus was detected by the PCR assays in 31 of 35 (89%) samples tested. Only 23 samples (66%) were positive by the IF method, and these samples were also positive by both the PCR-F and PCR-G assays. The 31 samples detected as positive by PCR originated from cattle presenting clinical signs of acute respiratory disease; the four PCR-negative samples originated from clinically asymptomatic neighboring cattle. All sampled animals subsequently seroconverted and became reactive to BRSV. Thus, the detection of BRSV by PCR correlated with clinical observations and was considerably more sensitive (66 versus 89%) than IF. These results indicate that both nested PCR assays provide rapid and sensitive means for the detection of BRSV infection in cattle. Considering its higher specificity, the PCR-F assay can be recommended as the method of choice in the analysis of clinical specimens of BRSV.",,"['Vilcek, S', 'Elvander, M', 'Ballagi-Pordány, A', 'Belák, S']",,,,
,PMC,Detection of porcine reproductive and respiratory syndrome virus and efficient differentiation between Canadian and European strains by reverse transcription and PCR amplification.,,PMC263966,,,"Two sets of oligonucleotide primers (1008PS-1009PR and 1010PLS-1011PLR) were designed according to the sequence of the nucleocapsid protein (N) gene of Quebec reference strain IAF-exp91 of porcine reproductive and respiratory syndrome virus (PRRSV). The primers were used in reverse transcription and PCR (RT-PCR) experiments for detection of viral genomic RNA either from infected porcine alveolar macrophages (PAM) or tissues from experimentally infected specific-pathogen-free pigs. Considering the high degree of variation detected between the nucleotide sequences of the N genes of IAF-exp91 and Lelystad virus (LV) strains of PRRSV, the primers 1008PS-1009PR were referred to as the specific primers, since they were chosen in such a manner that they could amplify only sequences from IAF-exp91 RNA and not from LV. On the other hand, the primer pair 1010PLS-1011PLR was common to both strains of PRRSV. When analyzed by agarose gel electrophoresis, the products of RT-PCR from each set of primers were resolved as single band of the predicted size, the specificity of amplified products being confirmed by Southern blotting with a specific IAF-exp91 N gene probe. No amplification was observed when RNA was extracted from uninfected PAM or from other porcine viruses. As expected, only the common primer pair was able to amplify RNA from the Quebec reference strain and two European strains (LV and Weybridge). The resulting bands displayed differences in electrophoretic mobilities due to the absence of 37 nucleotides in both European strains, thus allowing their differentiation from the IAF-exp91 strain. Most of the tissue culture-adapted Quebec isolates were detected with both primer pairs. The sensitivity of the enzymatic amplification method for detection of PRRSV from lung tissues was a 50% tissue culture infective dose of 5. RT-PCR was found to be more sensitive than indirect immunofluorescence assay for detection of PRRSV in tissues from experimentally infected pigs and as sensitive as virus isolation in PAM, especially when combined with Southern blotting with the digoxigenin-labeled N probe and chemiluminescence detection.",,"['Mardassi, H', 'Wilson, L', 'Mounir, S', 'Dea, S']",,,,
,PMC,Enhanced competitiveness of tomato bushy stunt virus defective interfering RNAs by segment duplication or nucleotide insertion.,,PMC237020,,,"We have analyzed atypical tomato bushy stunt virus defective interfering (DI) RNA species which accumulated during a passage series in protoplasts. We present a rationale for the order of appearance of these molecules and show, using competition assays, that either segment duplication or single nucleotide insertion can enhance DI RNA competitiveness. Possible mechanisms for the introduction of the modifications observed in these DI RNAs are discussed.",,"['White, K A', 'Morris, T J']",,,,
,PMC,The sequences of and distance between two cis-acting signals determine the efficiency of ribosomal frameshifting in human immunodeficiency virus type 1 and human T-cell leukemia virus type II in vivo.,,PMC237019,,,"We have analyzed in cell culture the sequence elements that control the level of ribosomal frameshifting in the human T-cell leukemia virus type II (HTLV-2) gag-pro junction. The slippery sequence of HTLV-2 is sufficient to dictate a basal level of frameshifting. This level is enhanced by its upstream sequence context and by the downstream stem-loop structure which is located at an optimal distance of 7 bases. Frameshifting in human immunodeficiency virus gag-pol is similar to that of HTLV-2 gag-pro. However, experiments using hybrid cassettes of HTLV-2 and human immunodeficiency virus type 1 frameshift elements show that while the slippery sequence of HTLV-2 is less efficient, the stem-loop structure is a more efficient enhancer.",,"['Kollmus, H', 'Honigman, A', 'Panet, A', 'Hauser, H']",,,,
,PMC,Genetic analysis of the nsP3 region of Sindbis virus: evidence for roles in minus-strand and subgenomic RNA synthesis.,,PMC236982,,,"Sindbis virus nonstructural polyproteins and their cleavage products are believed to be essential components of viral RNA replication and transcription complexes. Although numerous studies have investigated the effect of mutations in nsP1-, nsP2-, and nsP4-coding regions on Sindbis virus-specific RNA synthesis, relatively little is known about the function of the region encoding nsP3. nsP3 is a phosphoprotein comprising two regions: an N-terminal portion which is highly conserved among alphaviruses and a C-terminal portion which is not conserved, varying both in sequence and in length. We have constructed a library of random linker insertion mutations in the nsP3-coding region and characterized selected viable mutants. Initially, 126 mutants containing insertions in the conserved region and 23 with insertions in the nonconserved region were screened for temperature-sensitive (ts) plaque formation or for significant differences in plaque morphology. All nonconserved-region mutants were similar to the parental virus, whereas 13 of those in the conserved region were either ts or exhibited altered plaque phenotypes. Ten of these 13 mutants were ts for plaque formation as well as RNA accumulation at 40 degrees C. Highly ts mutants CR3.36 and CR3.39 were defective in their ability to synthesize minus-strand RNAs at the nonpermissive temperature. The CR3.36 and CR3.39 insertion mutations localized to different regions near nsP3 residues 58 and 226, respectively. CR3.39 was able to complement ts mutants from Sindbis virus complementation groups A, B, F, and G. Another mutant isolated from the library, CR3.34, while not ts for plaque formation or RNA synthesis, formed smaller plaques and was defective in subgenomic RNA synthesis at all temperatures examined. These results suggest a role for nsP3 or nsP3-containing polyproteins in the synthesis of viral minus-strand and subgenomic RNAs.",,"['LaStarza, M W', 'Lemm, J A', 'Rice, C M']",,,,
,PMC,A 100-kilodalton polypeptide encoded by open reading frame (ORF) 1b of the coronavirus infectious bronchitis virus is processed by ORF 1a products.,,PMC236981,,,"The genome-length mRNA (mRNA 1) of the coronavirus infectious bronchitis virus (IBV) contains two large open reading frames (ORFs), 1a and 1b, with the potential to encode polypeptides of 441 and 300 kDa, respectively. The downstream ORF, ORF 1b, is expressed by a ribosomal frameshifting mechanism. In an effort to detect viral polypeptides encoded by ORF 1b in virus-infected cells, immunoprecipitations were carried out with a panel of region-specific antisera. A polypeptide of approximately 100 kDa was precipitated from IBV-infected, but not mock-infected, Vero cells by one of these antisera (V58). Antiserum V58 was raised against a bacterially expressed fusion protein containing polypeptide sequences encoded by ORF 1b nucleotides 14492 to 15520; it recognizes specifically the corresponding in vitro-synthesized target protein. A polypeptide comigrating with the 100,000-molecular-weight protein (100K protein) identified in infected cells was also detected when the IBV sequence from nucleotides 8693 to 16980 was expressed in Vero cells by using a vaccinia virus-T7 expression system. Deletion analysis revealed that the sequence encoding the C terminus of the 100K polypeptide lies close to nucleotide 15120; it may therefore be generated by proteolysis at a potential QS cleavage site encoded by nucleotides 15129 to 15135. In contrast, expression of IBV sequences from nucleotides 10752 to 16980 generated two polypeptides of approximately 62 and 235 kDa, which represent the ORF 1a stop product and the 1a-1b fused product generated by a frameshifting mechanism, respectively, but no processed products were observed. Since the putative picornavirus 3C-like proteinase domain is located in ORF 1a between nucleotides 8937 and 9357, this observation suggests that deletion of the picornavirus 3C-like proteinase domain and surrounding regions abolishes processing of the 1b polyprotein. In addition, the in vitro translation and in vivo transfection studies also indicate that the ORF 1a region between nucleotides 8763 and 10720 contains elements that down-regulate the expression of ORF 1b.",,"['Liu, D X', 'Brierley, I', 'Tibbles, K W', 'Brown, T D']",,,,
,PMC,Proteolytic processing of the replicase ORF1a protein of equine arteritis virus.,,PMC236979,,,"To study the proteolytic processing of the equine arteritis virus (EAV) replicase open reading frame 1a (ORF1a) protein, specific antisera were raised in rabbits, with six synthetic peptides and a bacterial fusion protein as antigens. The processing of the EAV ORF1a product in infected cells was analyzed with Western blot (immunoblot) and immunoprecipitation techniques. Additional information was obtained from transient expression of ORF1a cDNA constructs. The 187-kDa ORF1a protein was found to be subject to at least five proteolytic cleavages. The processing scheme, which covers the entire ORF1a protein, results in cleavage products of approximately 29, 61, 22, 31, 41, and 3 kDa, which were named nonstructural proteins (nsps) 1 through 6, respectively. Pulse-chase experiments revealed that the cleavages at the nsp1/2 and nsp2/3 junctions are the most rapid processing steps. The remaining nsp3456 precursor is first cleaved at the nsp4/5 site. Final processing of the nsp34 and nsp56 intermediates is extremely slow. As predicted from previous in vitro translation experiments (E. J. Snijder, A. L. M. Wassenaar, and W. J. M. Spaan, J. Virol. 66:7040-7048, 1992), a cysteine protease domain in nsp1 was shown to be responsible for the nsp1/2 cleavage. The other processing steps are carried out by the putative EAV serine protease in nsp4 and by a third protease, which remains to be identified.",,"['Snijder, E J', 'Wassenaar, A L', 'Spaan, W J']",,,,
,PMC,Swine testis cells contain functional heparan sulfate but are defective in entry of herpes simplex virus.,,PMC236968,,,"Herpes simplex virus (HSV) enters and infects most cultured cells. We have found that swine testis cells (ST) produce yields of infectious HSV-1 up to four orders of magnitude lower than those of human embryonic lung (HEL) and HEp-2 cells because of a defect in virus entry. For ST cells, virus binding is reduced, DNA from input virus cannot be detected, and virus proteins are not synthesized. Polyethylene glycol treatment of ST cells after exposure to HSV allows viral entry, protein synthesis, and productive infection. Transfection of viral genomic DNA that bypasses the normal entry process produces similar yields of infectious virus from ST, HEL, and HEp-2 cells. Therefore, all three cell lines can support the HSV replicative cycle. Biochemical analyses and inhibition of sulfation by sodium chlorate treatment show that ST cells contain amounts and types of heparan sulfate (HS) similar to those of highly susceptible cells. HSV infection of sodium chlorate-treated HEL and ST cells indicates the presence of a second, non-HS receptor(s) on susceptible HEp-2 and HEL cells that is missing, or not functional, on poorly susceptible ST cells. We conclude that ST cells are defective in HSV entry, contain functional HS, but lack a functional non-HS receptor(s) required for efficient HSV-1 entry. Further, ST cells provide a novel resource that can be used to identify, isolate, and characterize an HSV non-HS receptor(s) and its role in the entry and tropism of this important human pathogen.",,"['Subramanian, G', 'McClain, D S', 'Perez, A', 'Fuller, A O']",,,,
,PMC,The human astrovirus RNA-dependent RNA polymerase coding region is expressed by ribosomal frameshifting.,,PMC236959,,,"The genomic RNA of human astrovirus serotype 1 (HAst-1) contains three open reading frames (ORFs), 1a, 1b, and 2. ORF 1b is located downstream of, and overlaps, 1a, and it has been suggested on the basis of sequence analysis that expression of ORF 1b is mediated through -1 ribosomal frameshifting. To examine this possibility, a cDNA fragment containing the 1a-1b overlap region was cloned within a reporter gene and placed under the control of the bacteriophage SP6 promoter in a recombinant plasmid. Synthetic transcripts derived from this plasmid, when translated in the rabbit reticulocyte lysate cell-free system, specified the synthesis of polypeptides whose size and antibody reactivity were consistent with an efficient -1 ribosomal frameshift event at the overlap region. The HAst-1 frameshift signal has two essential components, a heptanucleotide slippery sequence, A6C, and a stem-loop structure in the RNA. The presence of this structure was confirmed by complementary and compensatory mutation analysis and by direct structure probing with single- and double-stranded RNA-specific reagents. The HAst-1 frameshift signal, like that present at the overlap of the gag and pro genes of the retrovirus human T-cell lymphotrophic virus type II, does not involve the formation of an RNA pseudoknot.",,"['Marczinke, B', 'Bloys, A J', 'Brown, T D', 'Willcocks, M M', 'Carter, M J', 'Brierley, I']",,,,
,PMC,Cytokine induction during T-cell-mediated clearance of mouse hepatitis virus from neurons in vivo.,,PMC236949,,,"To investigate the mechanism by which viruses are cleared from neurons in the central nervous system, we have utilized a mouse model involving infection with a neurotropic variant of mouse hepatitis virus (OBLV60). After intranasal inoculation, OBLV60 grew preferentially in the olfactory bulbs of BALB/c mice. Using in situ hybridization, we found that viral RNA localized primarily in the outer layers of the olfactory bulb, including neurons of the mitral cell layer. Virus was cleared rapidly from the olfactory bulb between 5 and 11 days. Athymic nude mice failed to eliminate the virus, demonstrating a requirement for T lymphocytes. Immunosuppression of normal mice with cyclophosphamide also prevented clearance. Both CD4+ and CD8+ T-cell subsets were important, as depletion of either of these subsets delayed viral clearance. Gliosis and infiltrates of CD4+ and CD8+ cells were detected by immunohistochemical analysis at 6 days. The role of cytokines in clearance was investigated by using an RNase protection assay for interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, tumor necrosis factor alpha (TNF-alpha), TNF-beta, and gamma interferon (IFN-gamma). In immunocompetent mice there was upregulation of RNA for IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, and IFN-gamma at the time of clearance. Nude mice had comparable increases in these cytokine messages, with the exception of IFN-gamma. Induction of major histocompatibility complex class I (MHC-I) molecules on cells in infected brains was demonstrated by immunohistochemical analyses in normal and nude mice, suggesting that IFN-gamma may not be necessary for induction of MHC-I on neural cells in vivo.",,"['Pearce, B D', 'Hobbs, M V', 'McGraw, T S', 'Buchmeier, M J']",,,,
,PMC,Localization of neutralizing epitopes and the receptor-binding site within the amino-terminal 330 amino acids of the murine coronavirus spike protein.,,PMC236940,,,"To localize the epitopes recognized by monoclonal antibodies (MAbs) specific for the S1 subunit of the murine coronavirus JHMV spike protein, we have expressed S1 proteins with different deletions from the C terminus of S1. S1utt is composed of the entire 769-amino-acid (aa) S1 protein; S1NM, S1N, S1n(330), and S1n(220) are deletion mutants with 594, 453, 330, and 220 aa from the N terminus of the S1 protein. The expressed S1 deletion mutant proteins were examined for reactivities to a panel of MAbs. All MAbs classified in groups A and B, those reactive to most mouse hepatitis virus (MHV) strains and those specific for isolate JHMV, respectively, recognized S1N(330) and the larger S1 deletion mutants but failed to react with S1N(220). MAbs in group C, specific for the larger S protein of JHMV, reacted only with the S1utt protein without any deletion. These results indicated that the domain composed of the N-terminal 330 aa comprised the cluster of conformational epitopes recognized by MAbs in groups A and B. It was also shown that the epitopes of MAbs in group C were not restricted to the region missing in the smaller S protein. These results together with the fact that all MAbs in group B retained high neutralizing activity suggested the possibility that the N-terminal 330 aa are responsible for binding to the MHV-specific receptors. In investigate this possibility, we expressed the receptor protein and examined the binding of each S1 deletion mutant to the receptor. It was demonstrated that the S1N(330) protein as well as other S1 deletion mutants larger than S1N(330) bound to the receptor. These results indicated that a domain composed of 330 aa at the N terminus of the S1 protein is responsible for binding to the MHV-specific receptor.",,"['Kubo, H', 'Yamada, Y K', 'Taguchi, F']",,,,
,PMC,Immunohistochemical detection of swine influenza virus and porcine reproductive and respiratory syndrome virus in porcine proliferative and necrotizing pneumonia cases from Québec.,,PMC1686704,,,,,"['Larochelle, R', 'Sauvageau, R', 'Magar, R']",,,,
,PMC,"Identification of astrovirus serotypes from children treated at the Hospitals for Sick Children, London 1981-93.",,PMC2271231,,,"An enzyme immunoassay (EIA) for astrovirus type 1 together with immune electronmicroscopy (IEM) was used to type a collection of 162 astroviruses obtained from 1981-93 from children with diarrhoea. The EIA was found to be specific for astrovirus type 1. Astrovirus types 2-4 were typed by IEM. Astrovirus type 1 was the prevalent serotype 107/125 (86%), followed by type 3 (8%), type 4 (6%) and type 2 (1%). Six samples containing astrovirus could not be typed or detected by EIA because they were coated with coproantibodies; 11 others were not identified. Virus particles could no longer be detected in 15/162 (9%) samples following storage for > or = 2 years. Selected samples containing astrovirus types 1-4 were passaged in CaCO2 cells and their identity confirmed by one or both assays. One sample was shown to have remained viable for 10 years when stored as an aqueous suspension at -20 degrees C. Two patients with severe combined immune deficiency disease (SCID) were shown to be excreting astrovirus type 1 for 32 and 102 days respectively. One child was simultaneously shedding rotavirus and the other child was excreting adenovirus.",,"['Noel, J.', 'Cubitt, D.']",,,,
,PMC,A mathematical model of detection and dynamics of porcine transmissible gastroenteritis.,,PMC2271214,,,"Transmissible gastroenteritis (TGE) is a viral disease causing dehydration, diarrhoea and death in pigs. The disease is widespread in pig-producing areas of the world but does not occur in Australia. A mathematical model of TGE spread within a pig herd is proposed and calibrated by reference to published data. The model is then applied to two situations of special interest; first to estimate the delay before detection of TGE (6 to over 30 days) when infection is first introduced into a herd of domestic or feral pigs, and second the effect of the disease in a population of feral pigs (could become endemic if transmission is high).",,"Hone, J.",,,,
,PMC,Determinants essential for the transmissible gastroenteritis virus-receptor interaction reside within a domain of aminopeptidase-N that is distinct from the enzymatic site.,,PMC236465,,,"The swine-specific coronavirus transmissible gastroenteritis virus (TGEV) uses pig aminopeptidase-N (pAPN) as a cellular receptor. We showed that the human aminopeptidase-N (hAPN) cannot substitute for pAPN in this respect, although the two enzymes have 80% amino acid sequence identity. In order to map the TGEV binding site on pAPN, we constructed a series of APN cDNA chimeras between pAPN and hAPN and analyzed them for their capacity to confer infectivity. The region between residues 717 and 813 was found to be essential for infectivity. This region also contains the epitopes for three TGEV-blocking monoclonal antibodies directed against pAPN. These data support the view that the catalytic site and the TGEV receptor site are located in different domains. Moreover, APN inhibitors and mutations in the catalytic site had no obvious effect on permissiveness for virus, thus providing evidence that the APN enzymatic activity is not involved in the process of infection.",,"['Delmas, B', 'Gelfi, J', 'Kut, E', 'Sjöström, H', 'Noren, O', 'Laude, H']",,,,
,PMC,Intracellular manipulation of disulfide bond formation in rotavirus proteins during assembly.,,PMC236464,,,"Rotavirus undergoes a unique mode of assembly in the rough endoplasmic reticulum (RER) of infected cells. Luminal RER proteins undergo significant cotranslational and posttranslational modifications, including disulfide bond formation. Addition of a reducing agent (dithiothreitol [DTT]) to rotavirus-infected cells did not significantly inhibit translation or disrupt established disulfide bonds in rotavirus proteins but prevented the formation of new disulfide bonds and infectious viral progeny. In DTT-treated, rotavirus-infected cells, all vp4, vp6, and ns28 epitopes but no vp7 epitopes were detected by immunohistochemical staining with a panel of monoclonal antibodies. When oxidizing conditions were reestablished in DTT-treated cells, intramolecular disulfide bonds in vp7 were rapidly and correctly established with the restoration of antigenicity, although prolonged DTT treatment led to the accumulation of permanently misfolded vp7. Electron microscopy revealed that cytosolic assembly of single-shelled particles and budding into the ER was not affected by DTT treatment but that outer capsid assembly was blocked, leading to the accumulation of single-shelled and enveloped intermediate subviral particles in the RER lumen.",,"['Svensson, L', 'Dormitzer, P R', 'von Bonsdorff, C H', 'Maunula, L', 'Greenberg, H B']",,,,
,PMC,Coronavirus leader RNA regulates and initiates subgenomic mRNA transcription both in trans and in cis.,,PMC236413,,,"Mouse hepatitis virus (MHV), a coronavirus, utilizes a discontinuous transcription mechanism for subgenomic mRNA synthesis. Previous studies (C.-L. Liao and M. C. C. Lai, J. Virol. 68:4727-4737, 1994) have demonstrated that an upstream cis-acting leader sequence serves as a transcriptional enhancer, but the mechanism of transcriptional regulation is not clear. In this study, we constructed a series of defective interfering (DI) RNAs containing the chloramphenicol acetyltransferase (CAT) gene behind a differentially expressed transcription initiation (intergenic) sequence (for mRNA2-1). These DI RNAs had different copy numbers of the UCUAA pentanucleotide sequence at the 3' end of the leader. Transfection of these DI RNA constructs into cells infected with a helper MHV, which contains either two or three UCUAA copies at the 3' end of the leader, resulted in differential expression of CAT activities. We demonstrated that the copy number of UCUAA repeats in the leaders of both helper viral and DI RNAs affected the level of CAT activity, suggesting that MHV leader RNA could regulate both in trans and in cis the transcription of subgenomic mRNAs. The leader RNA of subgenomic mRNAs was derived from either the trans- or the cis-acting leader. Furthermore, insertion of a UA-rich sequence (UUUAUAAAC) immediately downstream of the leader in DI RNA, to match the sequence of helper viral RNA, enhanced the CAT activity by threefold, suggesting that this nine-nucleotide sequence is a cis-acting element. Interestingly, when the nine-nucleotide sequence was absent in DI RNA, the leaders of subgenomic mRNAs were exclusively derived from the helper virus. In contrast, when the nine-nucleotide sequence was present in DI RNA, the leaders were derived from both helper viral and DI RNAs. These results suggest that the nine-nucleotide sequence either is required for the leader RNA to initiate mRNA synthesis or, alternatively, serves as a transcription terminator for the leader RNA synthesis. However, when a constitutively expressed intergenic sequence (for mRNA7) was used, no difference in transcription efficiency was noted, regardless of the copy number of UCUAA in the DI RNA and helper virus. This study thus indicates that MHV subgenomic RNA transcription requires the interaction among the intergenic (promoter) sequence, a trans-acting leader, and a cis-acting leader sequence. A novel model of transcriptional regulation of coronavirus subgenomic mRNAs is presented.",,"['Zhang, X', 'Liao, C L', 'Lai, M M']",,,,
,PMC,Requirement of the 5'-end genomic sequence as an upstream cis-acting element for coronavirus subgenomic mRNA transcription.,,PMC236412,,,"We have developed a defective interfering (DI) RNA containing a chloramphenicol acetyltransferase reporter gene, placed behind an intergenic sequence, for studying subgenomic mRNA transcription of mouse hepatitis virus (MHV), a prototype coronavirus. Using this system, we have identified the sequence requirement for MHV subgenomic mRNA transcription. We show that this sequence requirement differs from that for RNA replication. In addition to the previously identified requirement for an intergenic (promoter) sequence, additional sequences from the 5' end of genomic RNA are required for subgenomic mRNA transcription. These upstream sequences include the leader RNA and a spacer sequence between the leader and intergenic sequence, which is derived from the 5' untranslated region and part of gene 1. The spacer sequence requirement is specific, since only the sequence derived from the 5' end of RNA genome, but not from other MHV genomic regions or heterologous sequences, could initiate subgenomic transcription from the intergenic sequence. These results strongly suggest that the wild-type viral subgenomic mRNAs (mRNA2 to mRNA7) and probably their counterpart subgenomic negative-sense RNAs cannot be utilized for mRNA amplification. Furthermore, we have demonstrated that a partial leader sequence present at the 5' end of genome, which lacks the leader-mRNA fusion sequence, could still support subgenomic mRNA transcription. In this case, the leader sequences of the subgenomic transcripts were derived exclusively from the wild-type helper virus, indicating that the MHV leader RNA initiates in trans subgenomic mRNA transcription. Thus, the leader sequence can enhance subgenomic transcription even when it cannot serve as a primer for mRNA synthesis. These results taken together suggest that the 5'-end leader sequence of MHV not only provides a trans-acting primer for mRNA initiation but also serves as a cis-acting element required for the transcription of subgenomic mRNAs. The identification of an upstream cis-acting element for MHV subgenomic mRNA synthesis defines a novel sequence requirement for regulating mRNA synthesis in RNA viruses.",,"['Liao, C L', 'Lai, M M']",,,,
,PMC,Coronavirus infections in the laboratory rat: degree of cross protection following immunization with a heterologous strain.,,PMC1263700,,,"One hundred and twenty-one specific pathogen-free male Wistar rats eight to ten weeks of age were used to evaluate the efficacy of Parker's rat coronavirus (PRC) in affording cross protection on subsequent challenge with virulent sialodacryoadenitis (SDA) virus. Sixty-two animals were inoculated intranasally on day 0 and 21 days later with approximately 10(2) median tissue culture infective doses (TCID50) of the tenth passage of PRC replicated in L-2 cells. Animals were selected at random postvaccination to evaluate the safety and efficacy of PRC by histopathology, immunohistochemistry and serology. At three and six months postvaccination (PV), vaccinated and seronegative control rats were inoculated intranasally with approximately 10(3) TCID50 doses of virulent SDA virus. Challenged rats were then killed at 6, 10 and 14 days postchallenge and necropsied. Evaluations were based on lesion indices in lacrimal and salivary glands and respiratory tract, the presence of viral antigen by immunohistochemistry, and antibody response. Lesions were observed in rats killed PV, but in general, they were significantly reduced compared with those present in seronegative animals post-exposure to virulent SDA virus (p < or = 0.05). However, they were still considered to be an unacceptable level for a routine vaccination procedure. Potvaccination antibody titers to rat coronavirus were evident in all animals tested at three or six months prior to challenge with SDA virus.(ABSTRACT TRUNCATED AT 250 WORDS)",,"['Bihun, C G', 'Percy, D H']",,,,
,PMC,Mutational analysis of sequences in the recF gene of Escherichia coli K-12 that affect expression.,,PMC205599,,,"The level of translation of recF-lacZ fusions is reduced 20-fold by nucleotides 49 to 146 of recF. In this region of recF, we found a previously described ribosome-interactive sequence called epsilon and a hexapyrimidine tract located just upstream of the epsilon sequence. Mutational studies indicate that the hexapyrimidine sequence is involved in at least some of the reduced translation. When the hexapyrimidine sequence is mutant, mutating epsilon increases the level of translation maximally. We ruled out the possibility that ribosome frameshifting explains most of the effect of these two sequences on expression and suspect that multiple mechanisms may be responsible. In a separate report, we show that mutations in the hexapyrimidine tract and epsilon increase expression of the full-sized recF gene.",,"['Sandler, S J', 'Clark, A J']",,,,
,PMC,Three new isolates of porcine respiratory coronavirus with various pathogenicities and spike (S) gene deletions.,,PMC263803,,,"Three new isolates of porcine respiratory coronavirus (PRCV) were isolated and partially characterized. These PRCV isolates showed a selective tropism for respiratory tissue and were antigenically related to transmissible gastroenteritis virus. PCR amplification of the 5' half of the spike (S) genes of the three PRCV isolates indicated that a large deletion, characteristic of PRCV, was present. By using cDNA probes specific for the transmissible gastroenteritis virus S gene, the PCR products were shown to be specific in a Southern blot. The three new PRCV isolates were shown to vary in S gene deletion size. In a separate study, these isolates have also been shown to vary in pathogenicity. These new PRCV isolates should serve as important tools in gaining a better understanding of the pathogenesis of coronavirus infections.",,"['Vaughn, E M', 'Halbur, P G', 'Paul, P S']",,,,
,PMC,"Bgp2, a new member of the carcinoembryonic antigen-related gene family, encodes an alternative receptor for mouse hepatitis viruses.",,PMC236379,,,"Murine coronaviruses such as mouse hepatitis virus (MHV) infect mouse cells via cellular receptors that are isoforms of biliary glycoprotein (Bgp) of the carcinoembryonic antigen gene family (G. S. Dveksler, C. W. Dieffenbach, C. B. Cardellichio, K. McCuaig, M. N. Pensiero, G.-S. Jiang, N. Beauchemin, and K. V. Holmes, J. Virol. 67:1-8, 1993). The Bgp isoforms are generated through alternative splicing of the mouse Bgp1 gene that has two allelic forms called MHVR (or mmCGM1), expressed in MHV-susceptible mouse strains, and mmCGM2, expressed in SJL/J mice, which are resistant to MHV. We here report the cloning and characterization of a new Bgp-related gene designated Bgp2. The Bgp2 cDNA allowed the prediction of a 271-amino-acid glycoprotein with two immunoglobulin domains, a transmembrane, and a putative cytoplasmic tail. There is considerable divergence in the amino acid sequences of the N-terminal domains of the proteins coded by the Bgp1 gene from that of the Bgp2-encoded protein. RNase protection assays and RNA PCR showed that Bgp2 was expressed in BALB/c kidney, colon, and brain tissue, in SJL/J colon and liver tissue, in BALB/c and CD1 spleen tissue, in C3H macrophages, and in mouse rectal carcinoma CMT-93 cells. When Bgp2-transfected hamster cells were challenged with MHV-A59, MHV-JHM, or MHV-3, the Bgp2-encoded protein served as a functional MHV receptor, although with a lower efficiency than that of the MHVR glycoprotein. The Bgp2-mediated virus infection could not be inhibited by monoclonal antibody CC1 that is specific for the N-terminal domain of MHVR. Although CMT-93 cells express both MHVR and Bgp2, infection with the three strains of MHV was blocked by pretreatment with monoclonal antibody CC1, suggesting that MHVR was the only functional receptor in these cells. Thus, a novel murine Bgp gene has been identified that can be coexpressed in inbred mice with the Bgp1 glycoproteins and that can serve as a receptor for MHV strains when expressed in transfected hamster cells.",,"['Nédellec, P', 'Dveksler, G S', 'Daniels, E', 'Turbide, C', 'Chow, B', 'Basile, A A', 'Holmes, K V', 'Beauchemin, N']",,,,
,PMC,First peptide vaccine providing protection against viral infection in the target animal: studies of canine parvovirus in dogs.,,PMC236377,,,"A synthetic peptide vaccine which protects dogs against challenge with virulent canine parvovirus is described. The amino acid sequence used was discovered in previous studies on the immunogenic properties of previously mapped antigenic sites and represents the amino-terminal region of viral protein VP2. As with marker vaccines, it is possible to discriminate between vaccinated dogs that have not been exposed to the virus and dogs that have been infected with the virus. The protective mechanism can be explained by a humoral response against the peptide aided by T-cell epitopes contained in the carrier protein used for peptide coupling. This is the first example of a synthetic peptide vaccine that induces protection in target animals.",,"['Langeveld, J P', 'Casal, J I', 'Osterhaus, A D', 'Cortés, E', 'de Swart, R', 'Vela, C', 'Dalsgaard, K', 'Puijk, W C', 'Schaaper, W M', 'Meloen, R H']",,,,
,PMC,Identification and analysis of the pseudoknot-containing gag-pro ribosomal frameshift signal of simian retrovirus-1.,,PMC523688,,,"The pro and pol genes of simian retrovirus-1 (SRV-1) are expressed as parts of a fusion protein generated by -1 ribosomal frameshifting. To investigate the requirements for frameshifting at the gag-pro overlap, we have inserted a stretch of 58 nucleotides containing the proposed frameshift signal into a plasmid that allows monitoring of translation in all three reading frames. In vitro translation of mRNAs derived from this plasmid indicated that the 58 nucleotides from the SRV-1 gag-pro overlap were sufficient to induce an efficient -1 shift in a heterologous context. Mutational analysis demonstrated that the slip site is formed at the heptanucleotide G GGA AAC. The frameshift efficiency of the wild type sequence in rabbit reticulocyte lysate was 23%. A second component of the frameshift signal is formed by a pseudoknot seven bases downstream of the slip site. The presence of this pseudoknot was confirmed by mutational analysis, employing complementary and compensatory base changes, and by probing the structure of short RNA transcripts containing the frameshift signal. Adding increasing amounts of an SRV-1 pseudoknot containing RNA transcript to a translation reaction programmed with an SRV-1 frameshift reporter mRNA had no effect on the frameshift efficiency, arguing against the role of a specific pseudoknot-recognising factor in the frameshifting process.",,"['ten Dam, E', 'Brierley, I', 'Inglis, S', 'Pleij, C']",,,,
,PMC,CS31A capsule-like antigen as an exposure vector for heterologous antigenic determinants.,,PMC186544,,,"CS31A is a multimeric surface protein surrounding certain enterotoxigenic and septicemic bovine Escherichia coli strains. The possibility of using CS31A as a carrier of foreign antigenic determinants was investigated. Introduction of heterologous viral epitopes into the CS31A major subunit, ClpG, was successfully performed in the V3 region of the molecule which encodes for an immunodominant linear epitope. E. coli K-12 strains producing the hybrid CS31A molecules or the purified chimeric proteins were used for mice immunization. By using the C epitope derived from the S protein of the porcine transmissible gastroenteritis virus, significant antiviral antibody titers were elicited and seroneutralization of the virus was demonstrated, confirming that the molecular environment in V3 is favorable for antigen presentation. These results indicate that synthesis of CS31A hybrid proteins by the wild-type strain 31A could become a powerful tool for the development of oral vaccines directed against mucosal pathogens.",,"['Bousquet, F', 'Martin, C', 'Girardeau, J P', 'Méchin, M C', 'Der Vartanian, M', 'Laude, H', 'Contrepois, M']",,,,
,PMC,Subgenomic RNA synthesis directed by a synthetic defective interfering RNA of mouse hepatitis virus: a study of coronavirus transcription initiation.,,PMC236870,,,"We have used a full-length cDNA clone of a mouse hepatitis virus strain A59 defective interfering (DI) RNA, pMIDI-C, and cassette mutagenesis to study the mechanism of coronavirus subgenomic mRNA synthesis. Promoter sequences closely resembling those of subgenomic mRNAs 3 and 7 were inserted into MIDI-C. Both subgenomic RNA promoters gave rise to the synthesis of a subgenomic DI RNA in virus-infected and DI RNA-transfected cells. From a mutagenic analysis of the promoters we concluded the following. (i) The extent of base pairing between the leader RNA and the intergenic promoter sequence does not control subgenomic RNA abundance. (ii) Promoter recognition does not rely on base pairing only. Presumably, transcription initiation requires recognition of the promoter sequence by the transcriptase. (iii) Fusion of leader and body sequences takes place at multiple--possibly random--sites within the intergenic promoter sequence. A model is presented in which, prior to elongation, the leader RNA is trimmed by a processive 3'-->5' nuclease.",,"['van der Most, R G', 'de Groot, R J', 'Spaan, W J']",,,,
,PMC,Identification of minireovirus as a Norwalk-like virus in pediatric patients with gastroenteritis.,,PMC236832,,,"In 1977, 30- to 32-nm virus-like particles, named minireovirus because of their unique morphologic appearance, were detected by electron microscopy in the stools of infants and young children with gastroenteritis. Sequence analysis of approximately 2,800 consecutive bases derived from overlapping PCR clones of a recent minireovirus clinical isolate showed 52% nucleotide sequence identity with the Norwalk virus sequence and, in addition, demonstrated that the genomic organizations of these two viruses were similar. Our data show that minireovirus is a Norwalk-like virus and should now also be included in the Caliciviridae family.",,"['Lew, J F', 'Petric, M', 'Kapikian, A Z', 'Jiang, X', 'Estes, M K', 'Green, K Y']",,,,
,PMC,Distribution and trafficking of JHM coronavirus structural proteins and virions in primary neurons and the OBL-21 neuronal cell line.,,PMC236780,,,"The neurotropic murine coronavirus JHM is capable of inducing various forms of neurologic diseases, including demyelination. Neurons have been shown to act as a repository site at the early stages of the disease process (O. Sorensen and S. Dales, J. Virol. 56:434-438, 1985). JHM virus (JHMV) replication and trafficking of viral proteins and virions in cultured rat hippocampal neurons and a neuronal cell line, OBL-21, were examined, with an emphasis placed on the role of the microtubular network. We show here that JHMV spread within the central nervous system occurs transneuronally and that virus protein trafficking was dependent upon microtubules. Viral trafficking occurred asymmetrically, involving both the somatodendritic and the axonal domains. Thus coronavirus can be disseminated from neurons at either the basolateral or the apical domains. A specific interaction between antibodies derived against the microtubule-associated protein tau and JHMV nucleocapsid protein (N) was observed, which can presumably be explained by an overall amino acid similarity of 44% and an identity of 20% between proteins N and tau, with optimal alignment at the microtubule binding domain of tau. Collectively, our data suggest an important role of the microtubule network in viral protein trafficking and distribution. They also draw attention to protein sequence mimicry of a cell component by this coronavirus as one strategy for making use of the host's functions on behalf of the virus.",,"['Pasick, J M', 'Kalicharran, K', 'Dales, S']",,,,
,PMC,Why is CpG suppressed in the genomes of virtually all small eukaryotic viruses but not in those of large eukaryotic viruses?,,PMC236777,,,"Dinucleotide over- and underrepresentation is evaluated in all available completely sequenced DNA or RNA viral genomes, ranging in size from 3 to 250 kb (available RNA viruses fall into the small-virus category). The dinucleotide CpG is statistically underrepresented (suppressed) in all but four of the small viruses (more than 75 with lengths of < 30 kb) but has normal relative abundances in most large viruses (> or = 30 kb). Most retrotransposons in eukaryotic species also show low CpG relative abundances. Interpretations, especially in some cases of DNA viruses or viruses with a DNA intermediate, might relate to methylation effects and modes of viral integration and excision. Other possible contributing factors relate to dinucleotide stacking energies, special mutation mechanisms, and evolutionary events.",,"['Karlin, S', 'Doerfler, W', 'Cardon, L R']",,,,
,PMC,Modulation of major histocompatibility complex antigen expression by viral infection.,,PMC1887252,,,,,"Rinaldo, C. R.",,,,
,PMC,"Preliminary characterization of the structural proteins of the coronaviruses, sialodacryoadenitis virus and Parker's rat coronavirus.",,PMC1263673,,,"A procedure was developed for the partial purification of the rat coronaviruses, sialodacryoadenitis virus (SDAV) and Parker's rat coronavirus (PRC). The SDAV and PRC were replicated in L-2 cell monolayer cultures, precipitated with ammonium sulphate, and further concentrated using sucrose density gradient centrifugation. The major SDAV and PRC proteins were identified by immunoblotting and compared with those of the JHM strain of mouse hepatitis virus (MHV-JHM). Monoclonal antibodies (MAb) against the M protein of JHM recognized proteins interpreted to be slightly smaller in immunoblots of SDAV and PRC (22.8 vs 23K for JHM). Similarly, a monoclonal antibody against the JHM N protein reacted with proteins of 53K in SDAV and PRC (vs 56 K for JHM). Polyclonal antisera to all three viruses also cross-reacted with the M and N proteins. Some cross-reactivity amongst the S proteins was observed. Based on these data, the structural proteins of the rat coronaviruses, SDAV and PRC are closely related to those of MHV-JHM.",,"['Barker, M G', 'Percy, D H', 'Hovland, D J', 'MacInnes, J I']",,,,
,PMC,Psychoneuroimmunology: stress effects on pathogenesis and immunity during infection.,,PMC358318,,,"The mammalian response to stress involves the release of soluble products from the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. Cells of the immune system respond to many of the hormones, neurotransmitters, and neuropeptides through specific receptors. The function of the immune system is critical in the mammalian response to infectious disease. A growing body of evidence identifies stress as a cofactor in infectious disease susceptibility and outcomes. It has been suggested that effects of stress on the immune system may mediate the relationship between stress and infectious disease. This article reviews recent psychoneuroimmunology literature exploring the effects of stress on the pathogenesis of, and immune response to, infectious disease in mammals.",,"['Sheridan, J F', 'Dobbs, C', 'Brown, D', 'Zwilling, B']",,,,
,PMC,Expression of the Prevotella loescheii adhesin gene (plaA) is mediated by a programmed frameshifting hop.,,PMC205298,,,"The 2.4-kb plaA gene, which encodes a Prevotella loescheii galactoside-specific adhesin, contains a programmed frameshifting hop. The frameshift region consists of two UAA termination codons, two repeats of four identical bases between the terminators, and a stem-loop structure that has the potential to form a pseudoknot located downstream from the second UAA. The stem-loop and pseudoknot are features found in a number of retroviruses where frameshifting is a more common occurrence. The terminators, sequence repeats, and secondary structures were identified in both the P. loescheii plaA gene and the mRNA transcript. An in-frame fusion of the entire plaA frameshift region between codons 9 and 10 of the lacZ gene permitted relatively efficient expression (4 to 25% of that of the control) of beta-galactosidase in Escherichia coli.",,"['Manch-Citron, J N', 'London, J']",,,,
,PMC,Lethality of PE2 incorporation into Sindbis virus can be suppressed by second-site mutations in E3 and E2.,,PMC236746,,,"Sindbis virions contain two glycoproteins, E1 and E2. E2 is produced initially as a precursor, PE2, from which the amino-terminal 64 amino acids are cleaved by a cellular protease at a late stage in virion maturation. A mutation at E2 position 1 (Arg to Asn) was placed into Sindbis virus AR339 by site-directed mutagenesis of a full-length AR339 cDNA clone, pTRSB, to produce pTRSB-N. The mutation created a signal for N-linked glycosylation immediately adjacent to the PE2 cleavage signal. Virions derived from pTRSB-N were glycosylated at E2 position 1, and they quantitatively incorporated PE2 in place of E2. When pTRSB-N transcripts were electroporated into BHK-21 cells, TRSB-N particles were released with nearly normal efficiency; however, the specific infectivity of TRSB-N particles was very low. Analysis of seven infectious revertants of TRSB-N revealed that reversion was linked to (i) mutations that eliminated the signal for N-linked glycosylation and thus restored the PE2 cleavage phenotype or (ii) conservation of the PE2 cleavage defect combined with incorporation of suppressor mutations in E3 or E2. The genotype of each revertant was reconstructed in the genetic background of TRSB-N, and each reverting mutation also was replaced individually into the genetic background of wild-type virus (TRSB). Each PE2-containing revertant was attenuated in newborn CD-1 mice and replicated poorly in cultured mosquito cells (C6/36). Reverting mutations in the genetic background of TRSB did not reduce virulence in mice or growth in mosquito cells, suggesting that the phenotypes of attenuation in mice and reduced growth in mosquito cells were linked to failure of PE2 cleavage and not to the reverting mutations themselves.",,"['Heidner, H W', 'McKnight, K L', 'Davis, N L', 'Johnston, R E']",,,,
,PMC,Evidence for coronavirus discontinuous transcription.,,PMC236739,,,"Coronavirus subgenomic mRNA possesses a 5'-end leader sequence which is derived from the 5' end of genomic RNA and is linked to the mRNA body sequence. This study examined whether coronavirus transcription involves a discontinuous transcription step; the possibility that a leader sequence from mouse hepatitis virus (MHV) genomic RNA could be used for MHV subgenomic defective interfering (DI) RNA transcription was examined. This was tested by using helper viruses and DI RNAs that were easily distinguishable. MHV JHM variant JHM(2), which synthesizes a subgenomic mRNA encoding the HE gene, and variant JHM(3-9), which does not synthesize this mRNA, were used. An MHV DI RNA, DI(J3-9), was constructed to contain a JHM(3-9)-derived leader sequence and an inserted intergenic region derived from the region preceding the MHV JHM HE gene. DI(J3-9) replicated efficiently in JHM(2)- or JHM(3-9)-infected cells, whereas synthesis of subgenomic DI RNAs was observed only in JHM(2)-infected cells. Sequence analyses demonstrated that the 5' regions of both helper virus genomic RNAs and genomic DI RNAs maintained their original sequences in DI RNA-replicating cells, indicating that the genomic leader sequences derived from JHM(2) functioned for subgenomic DI RNA transcription. Replication and transcription of DI(J3-9) were observed in cells infected with an MHV A59 strain whose leader sequence was similar to that of JHM(2), except for one nucleotide substitution within the leader sequence. The 5' region of the helper virus genomic RNA and that of the DI RNA were the same as their original structures in virus-infected cells, and the leader sequence of DI(J3-9) subgenomic DI RNA contained the MHV A59-derived leader sequence. The leader sequence of subgenomic DI RNA was derived from that of helper virus; therefore, the genomic leader sequence had a trans-acting property indicative of a discontinuous step in coronavirus transcription.",,"['Jeong, Y S', 'Makino, S']",,,,
,PMC,Membrane anchoring domain of herpes simplex virus glycoprotein gB is sufficient for nuclear envelope localization.,,PMC236703,,,"We have used the glycoprotein gB of herpes simplex virus type 1 (gB-1), which buds from the inner nuclear membrane, as a model protein to study localization of membrane proteins in the nuclear envelope. To determine whether specific domains of gB-1 glycoprotein are involved in localization in the nuclear envelope, we have used deletion mutants of gB-1 protein as well as chimeric proteins constructed by replacing the domains of the cell surface glycoprotein G of vesicular stomatitis virus with the corresponding domains of gB. Mutant and chimeric proteins expressed in COS cells were localized by immunoelectron microscopy. A chimeric protein (gB-G) containing the ectodomain of gB and the transmembrane and cytoplasmic domains of G did not localize in the nuclear envelope. When the ectodomain of G was fused to the transmembrane and cytoplasmic domains of gB, however, the resulting chimeric protein (G-gB) was localized in the nuclear envelope. Substitution of the transmembrane domain of G with the 69 hydrophobic amino acids containing the membrane anchoring domain of gB allowed the hybrid protein (G-tmgB) to be localized in the nuclear envelope, suggesting that residues 721 to 795 of gB can promote retention of proteins in the nuclear envelope. Deletion mutations in the hydrophobic region further showed that a transmembrane segment of 21 hydrophobic amino acids, residues 774 to 795 of gB, was sufficient for localization in the nuclear envelope. Since wild-type gB and the mutant and chimeric proteins that were localized in the nuclear envelope were also retained in the endoplasmic reticulum, the membrane spanning segment of gB could also influence retention in the endoplasmic reticulum.",,"['Gilbert, R', 'Ghosh, K', 'Rasile, L', 'Ghosh, H P']",,,,
,PMC,Detection of bovine coronavirus and type A rotavirus in neonatal calf diarrhea and winter dysentery of cattle in Quebec: evaluation of three diagnostic methods.,,PMC1686320,,,"The use of direct electron microscopy, enzyme-linked immunosorbent assay, and protein A-gold immunoelectron microscopy for the identification of bovine coronavirus and type A rotavirus were examined. Two hundred and forty-nine samples from diarrheic calves and winter dysenteric cattle from seven geographic areas in Quebec were examined for the presence of viruses by direct electron microscopy of negatively stained preparations. In addition, all the samples were analyzed by enzyme-linked immunosorbent assay, and a random selection of 47 samples were also analyzed by protein A-gold immunoelectron microscopy. Thirty-nine percent of samples examined by direct electron microscopy contained viral particles; bovine coronavirus and type A rotavirus were the most common viruses involved. Overall agreement between any two of the methods used compared favorably with results obtained by others using similar methods. The presence of coronavirus and rotavirus in fecal samples obtained from neonatal calves and the presence of coronavirus in samples from winter dysenteric adult cattle suggested their etiological roles in the respective diseases. Furthermore, results from protein A-gold immunoelectron microscopy of coronavirus-like particles implied that a different coronavirus or some other viruses might be involved in these diseases. Finally, the efficiency of direct electron microscopy, enzyme-linked immunosorbent assay and protein A-gold immunoelectron microscopy as diagnostic tools is discussed.",,"['Athanassious, R', 'Marsolais, G', 'Assaf, R', 'Dea, S', 'Descôteaux, J P', 'Dulude, S', 'Montpetit, C']",,,,
,PMC,"Abnormalities in subset distribution, activation, and differentiation of T cells isolated from large intestine biopsies in HIV infection. The Berlin Diarrhoea/Wasting Syndrome Study Group.",,PMC1535074,,,"Intestinal T cells have a unique state of activation and differentiation which might specifically affect or be affected by HIV infection. Lymphocyte subsets in the peripheral blood are well characterized, but our knowledge about intestinal lymphocytes in HIV infection is incomplete. We therefore analysed lymphocytes isolated from large intestine biopsies of AIDS patients and controls by three-colour cytofluorometry. In the large intestine of HIV-infected patients CD4 T cells were reduced and CD8 T cells were increased compared with controls. Most of the CD8 T cells in the colorectal mucosa of AIDS patients were of the cytotoxic phenotype. Activated and resting CD4 T cells were similarly reduced, the expression of CD25 and HLA-DR of CD8 T cells was unaltered and increased, respectively. In intestinal CD4 T cells the expression of CD29 was decreased, but the expression of CD45RO and HML-1 was normal. CD8 T cells had a decreased expression of all these differentiation markers. Our findings demonstrate substantial alterations in subset distribution, activation, and differentiation of large intestine T cells, which may contribute to the secondary infections and malignancies commonly observed in the gut of AIDS patients.",,"['Schneider, T', 'Ullrich, R', 'Bergs, C', 'Schmidt, W', 'Riecken, E O', 'Zeitz, M']",,,,
,PMC,Proteolytic cleavage of bovine herpesvirus 1 (BHV-1) glycoprotein gB is not necessary for its function in BHV-1 or pseudorabies virus.,,PMC236625,,,"Glycoprotein B homologs represent the most highly conserved group of herpesvirus glycoproteins. They exist in oligomeric forms based on a dimeric structure. Despite the high degree of sequence and structural conservation, differences in posttranslational processing are observed. Whereas gB of herpes simplex virus is not proteolytically processed after oligomerization, most other gB homologs are cleaved by a cellular protease into subunits that remain linked via disulfide bonds. Proteolytic cleavage is common for activation of viral fusion proteins, and it has been shown that herpesvirus gB homologs are essential for membrane fusion events during infection, e.g., virus penetration and direct viral cell-to-cell spread. To analyze the importance of proteolytic cleavage for the function of gB homologs, we isolated a mutant bovine herpesvirus 1 (BHV-1) expressing a BHV-1 gB that is no longer proteolytically processed because of a deletion of the proteolytic cleavage site and analyzed its phenotype in cell culture. We showed previously that BHV-1 gB can functionally substitute for the homologous glycoprotein in pseudorabies virus (PrV), based on the isolation of a PrV gB-negative PrV recombinant that expresses BHV-1 gB (A. Kopp and T. C. Mettenleiter, J. Virol, 66:2754-2762, 1992). Therefore, we also isolated a mutant PrV lacking PrV gB but expressing a noncleavable BHV-1 gB. Our results show that cleavage of BHV-1 gB is not essential for its function in either a BHV-1 or a PrV background. Compared with the PrV recombinant expressing cleavable BHV-1 gB, deletion of the cleavage site in the recombinant PrV did not detectably alter the viral phenotype, as analyzed by plaque assays, one-step growth kinetics, and penetration kinetics. In the BHV-1 mutant, the uncleaved BHV-1 gB was functionally equivalent to the wild-type protein with regard to penetration and showed only slightly delayed one-step growth kinetics compared with parental wild-type BHV-1. However, the resulting plaques were significantly smaller, indicating a role for proteolytic cleavage of BHV-1 gB in cell-to-cell spread of BHV-1.",,"['Kopp, A', 'Blewett, E', 'Misra, V', 'Mettenleiter, T C']",,,,
,PMC,Translational frameshifting at the gag-pol junction of human immunodeficiency virus type 1 is not increased in infected T-lymphoid cells.,,PMC236606,,,"A frameshift event is necessary for expression of the products of the pol gene in a number of retroviruses, including human immunodeficiency virus type 1 (HIV-1). The basic signals necessary for frameshifting consist of a shifty sequence in which the ribosome slips and a downstream stimulatory structure which can be either a stem-loop or a pseudoknot. In HIV-1, much attention has been paid to the frameshift site itself, and only recently has the role of the downstream structure been examined. Here we used a luciferase-based experimental system to analyze in vivo the cis and trans factors potentially involved in controlling frameshifting efficiency at the gag-pol junction of HIV-1. We demonstrated that high-level frameshifting is dependent on the presence of a palindromic region located downstream of the site where the frameshift event takes place. Frameshifting efficiencies were found to be identical in mouse fibroblasts and the natural host cells of the virus, i.e., CD4+ human lymphoid cells. Furthermore, no increase in frameshifting was observed upon virus infection. Previous observations have shown that viral infection leads to specific alteration of tRNAs involved in translation of shifty sites (D. Hatfield, Y.-X. Feng, B.J. Lee, A. Rein, J.G. Levin, and S. Oroszlan, Virology 173:736-742, 1989). The results presented here strongly suggest that these modifications do not affect frameshifting efficiency.",,"['Cassan, M', 'Delaunay, N', 'Vaquero, C', 'Rousset, J P']",,,,
,PMC,How N-linked oligosaccharides affect glycoprotein folding in the endoplasmic reticulum.,,PMC301034,,,,,"Helenius, A",,,,
,PMC,Crystal structure of an idiotype-anti-idiotype Fab complex.,,PMC43211,,,"Anti-idiotypic monoclonal antibody 409.5.3 is raised against an antibody that neutralizes feline infectious peritonitis virus. This antibody, used as an immunogen, elicits the production of anti-anti-idiotypic antibodies that in turn neutralize the virus. The crystal structure of the complex between anti-idiotypic Fab 409.5.3 and idiotypic Fab fragment of virus-neutralizing antibody has been solved by molecular replacement using real-space Patterson search and filtering by Patterson correlation-coefficient refinement. The structure has been refined to an R value of 0.21 based on 21,310 unique reflections between 40.0 and 2.9 A. The three-dimensional structure reveals extensive, specific interactions that involve 118 van der Waals contacts and at least 9 probable hydrogen bonds. The two Fabs are rotated 61 degrees with respect to each other around the approximate long axis of the complex and are within 26 degrees being aligned along their major axes.",,"['Ban, N', 'Escobar, C', 'Garcia, R', 'Hasel, K', 'Day, J', 'Greenwood, A', 'McPherson, A']",,,,
,PMC,Pathogenicity of porcine respiratory coronavirus isolated in Québec.,,PMC1686726,,,"Porcine respiratory coronavirus (PRCV) is present in many countries, including Canada, but controversy still exists concerning its pathogenicity. Eight-week-old piglets were inoculated intratracheally with a Quebec PRCV isolate (1Q90). Two contact piglets were kept with the inoculated animals. Three animals served as control. Polypnea and dyspnea were the main clinical signs observed. Diffuse bronchioloalveolar damage occurred 24 hours postinoculation. Changes compatible with bronchointerstitial pneumonia were present six days postinoculation. The inoculated virus was recovered from the respiratory tract and mesenteric lymph nodes, but not from the digestive tract, of the inoculated as well as the contact piglets. No virus was isolated from the control piglets. The development of clinical signs and histopathological changes in inoculated as well as in contact piglets and the reisolation of the inoculated virus demonstrated that PRCV can be an important respiratory pathogen.",,"['Jabrane, A', 'Girard, C', 'Elazhary, Y']",,,,
,PMC,"Clinical, cerebrospinal fluid, and histological data from twenty-seven cats with primary inflammatory disease of the central nervous system.",,PMC1686724,,,"The purpose of this report is to present the clinical, cerebrospinal fluid (CSF) and histological data from 27 cats with inflammatory disease of the central nervous system (CNS). The cats were part of a study of 61 cats admitted to two university clinics over an eight-year period because of signs of CNS disease. The most frequent diseases were feline infectious peritonitis (FIP) (12/27) and suspected viral disease other than FIP (10/27). Typical CSF findings in cats with FIP were a protein concentration of greater than 2 g/L (200 mg/dL) and a white cell count of over 100 cells/microL, which consisted predominantly of neutrophils. In contrast, the CSF of cats with suspected viral disease had a protein concentration of less than 1 g/L (100 mg/dL) and a total white cell count of less than 50 cells/microL. In general, cats with FIP or suspected viral disease were less than four years of age. Neurological signs were usually multifocal in cats with FIP, but focal in cats with suspected viral disease. The CSF findings were variable in five other inflammatory diseases represented. Two cats with protozoan infection had normal CSF total cell counts but abnormal differential counts. The CSF findings were invaluable in differentiating FIP from other causes of inflammatory CNS disease.",,"['Rand, J S', 'Parent, J', 'Percy, D', 'Jacobs, R']",,,,
,PMC,Kin recognition between medial Golgi enzymes in HeLa cells.,,PMC394845,,,"The medial Golgi enzymes, N-acetylglucosaminyltransferase I (NAGT I) and mannosidase II (Mann II), and the trans Golgi enzyme, beta-1,4-galactosyltransferase (GalT) were each retained in the endoplasmic reticulum (ER) by grafting on the cytoplasmic tail of the p33 invariant chain. Transient and stable expression of p33/NAGT I in HeLa cells caused relocation of endogenous Mann II to the ER and transient expression of p33/Mann II had a similar effect on endogenous NAGT I. Neither of these endogenous medial enzymes were affected by transient expression of p33/GalT. These data provide strong evidence for kin recognition between medial Golgi enzymes and suggest a role for them in the organization of the Golgi stack.",,"['Nilsson, T', 'Hoe, M H', 'Slusarewicz, P', 'Rabouille, C', 'Watson, R', 'Hunte, F', 'Watzele, G', 'Berger, E G', 'Warren, G']",,,,
,PMC,Mimicry of a neutralizing epitope of the major outer membrane protein of Chlamydia trachomatis by anti-idiotypic antibodies.,,PMC186113,,,"The major outer membrane protein (MOMP) is a primary target antigen for the development of chlamydial vaccine. This protein is composed of four variable domains (I to IV) flanked by constant regions. Some of the variable domains contain antigenic determinants that elicit a neutralizing antibody response. Murine monoclonal antibodies (MAbs) against three nonoverlapping epitopes of MOMP were developed. One of these, called DP10, bound to all serovars, as shown by immunoblot analysis, and neutralized chlamydial infectivity for hamster kidney (HaK) cells in a complement-independent in vitro assay. Furthermore, analysis of the fine specificity of this MAb showed that it recognized a synthetic peptide contained within variable domain IV of the MOMP. Anti-idiotypic antibodies (aId) directed against this anti-MOMP MAb were produced in rabbits. These aId specifically bound to the relevant idiotype (DP10) and inhibited the binding of anti-MOMP MAb (DP10) to MOMP preparations in a dose-dependent fashion. The specificity of our aId for the binding site of anti-MOMP MAb is further suggested by the binding inhibition of affinity-purified aId to DP10 by the synthetic peptide defined by the idiotype. In addition, these aId also reacted with anti-MOMP antisera from rats and mice, suggesting an idiotypic cross-reactivity between these species. Finally, immunization of naive mice with aId induced an antibody response directed against the peptide defined by our anti-MOMP MAb and with neutralizing activity. Taken together, these data suggest that aId mimic a neutralization site on MOMP and could serve as a surrogate antigen to induce protective immunity against Chlamydia trachomatis.",,"['Brossay, L', 'Villeneuve, A', 'Paradis, G', 'Coté, L', 'Mourad, W', 'Hébert, J']",,,,
,PMC,Microvascular exudative hyperresponsiveness in human coronavirus-induced common cold.,,PMC474322,,,"BACKGROUND--The inflammatory response of the airway microcirculation in rhinitis and asthma may be recorded as luminal entry of plasma macromolecules (mucosal exudation). This study examines the exudative responsiveness of the subepithelial microvessels in subjects with and without common cold after inoculation with coronavirus. METHODS--The airway mucosa was exposed to exudative concentrations of histamine (40 and 400 micrograms/ml) before and six days after inoculation. To assess whether mucosal penetration of a topically applied agent was altered, nasal absorption of chromium-51 labelled ethylene diamine tetraacetic acid (51Cr-EDTA, MW 372) was also examined. A nasal pool technique kept the challenge and tracer solutes in contact with the same ipsilateral mucosal surface. Concentrations of albumin in lavage fluids were measured as an index of mucosal exudation of plasma. Nasal absorption of 51Cr-EDTA was determined by the cumulated 24 hour urinary excretion of radioactivity. RESULTS--Nine subjects developed common cold after coronavirus inoculation and 10 remained healthy. Histamine produced concentration dependent mucosal exudation of plasma in all subjects before and after coronavirus inoculation. In subjects with common cold, however, the histamine-induced mucosal exudation was significantly augmented compared with the group without common cold. This exudative hyperresponsiveness is not explained by an increased baseline exudation because the lavage regimen used produced comparably low baseline exudation in both groups of subjects, nor is it explained by an increased penetration of topical histamine because the ability of the nasal mucosa to absorb 51Cr-EDTA was not significantly increased in the subjects with common cold. CONCLUSIONS--An increased proclivity of the airway subepithelial microcirculation to respond with plasma exudation develops during coronavirus-induced common cold. This specific exudative hyperresponsiveness may be a feature of inflammatory airway diseases.",,"['Greiff, L.', 'Andersson, M.', 'Akerlund, A.', 'Wollmer, P.', 'Svensson, C.', 'Alkner, U.', 'Persson, C. G.']",,,,
,PMC,Crystallographic and cryo EM analysis of virion-receptor interactions,,PMC4140090,,,"Cryoelectron microscopy has been used to determine the first structure of a virus when complexed with its glycoprotein cellular receptor. Human rhinovirus 16 (HRV16) complexed with the two amino-terminal, immunoglobulin-like domains of the intercellular adhesion molecule-1 (ICAM-1) shows that ICAM-1 binds into the 12Å deep “canyon” on the surface of the virus. This is consistent with the prediction that the viral receptor attachment site lies in a cavity inaccessible to the host's antibodies. The atomic structures of HRV14 and CD4, homologous to HRV16 and ICAM-1, showed excellent correspondence with observed density, thus establishing the virus-receptor interactions.",,"['Rossmann, M. G.', 'Olson, N. H.', 'Kolatkar, P. R.', 'Oliveira, M. A.', 'Cheng, R. H.', 'Greve, J. M.', 'McClelland, A.', 'Baker, T. S.']",,,,
,PMC,"Porcine reproductive and respiratory syndrome virus: morphological, biochemical and serological characteristics of Quebec isolates associated with acute and chronic outbreaks of porcine reproductive and respiratory syndrome.",,PMC1263660,,,"Cytolytic and noncytolytic strains of the porcine reproductive and respiratory syndrome virus (PRRSV) were isolated in primary cultures of porcine alveolar macrophages (PAM) from lung homogenates of stillborn fetuses or blood samples of dyspneic piglets collected from Quebec pig farms having experienced acute or chronic outbreaks of PRRS. Serological identification of the virus was confirmed by indirect immunofluorescence and indirect protein A-gold immunoelectron microscopy using reference antiserum prepared from experimentally-infected specific pathogen free (SPF) piglets and monoclonal antibodies (MoAbs) directed against the p15 nucleocapsid (N) protein of the reference ATCC-VR2332 isolate. Intracytoplasmic enveloped viral particles that tended to accumulate into cytoplasmic vesicles were observed in the infected PAM; no budding was demonstrated at the level of the cytoplasmic membrane. The extracellular virions appeared as pleomorphic but mostly spherical enveloped particles, 50-72 nm in diameter (averaged diameter of 50 particles was 58.3 nm), with an isometric core about 25-30 nm. Buoyant density of the virus in CsCL density gradients was estimated to 1.18-1.20 g/mL. No hemagglutinating activity was demonstrated. Analysis of semipurified virions of isolate IAF-exp91 by radioimmunoprecipitation (RIPA) and Western immunoblotting experiments, using reference rabbit and porcine hyperimmune sera, revealed four major viral proteins, a predominant 15 kD N protein and three other proteins with predicted M(r_ of 19, 26 and 42 kD. Progeny viral particles produced in PRRSV-infected PAM in the presence of tunicamycin lacked the 42 kD protein, thus confirming its N-glycosylated nature. Immunoprecipitation experiments using the anti-ATCC-VR2332 MoAbs confirmed the close antigenic relationships between Quebec and American reference isolates of PRRSV.",,"['Mardassi, H', 'Athanassious, R', 'Mounir, S', 'Dea, S']",,,,
,PMC,Interaction of bovine respiratory syncytial virus with bovine alveolar macrophages in vivo: effects of virus infection upon selected cell functions.,,PMC1263658,,,"The effect of bovine respiratory syncytial virus (BRSV) upon alveolar macrophage (AM) function was investigated using an in vivo calf inoculation model. Alveolar macrophages were collected sequentially from live calves at multiple time points during the 14 day period following viral inoculation. Alveolar macrophages from bronchoalveolar lavage fluids were purified by density gradient centrifugation (> 95% AM) prior to in vitro evaluation of cell functions. There were significant but variable and inconsistent differences in the functions of AM from the BRSV inoculated calves compared to the control calves. Fc-receptor mediated phagocytosis was either increased or unchanged by BRSV inoculation. Nonopsonized phagocytosis was decreased during the early postinoculation period and later increased. There was a variable effect on AM phagosome lysosome fusion with increased fusion activity on postinoculation days 2 through 5, 7 and 12 but reduced activity on days 6 and 10. The AM respiratory burst, as measured by nitroblue tetrazolium dye reduction, was essentially unaffected with a reduction in activity on day 10 only. In this model, BRSV inoculation of calves primarily resulted in an alteration of the membrane associated phagocytic functions of the alveolar macrophages (p < 0.05).",,"['Olchowy, T W', 'Ames, T R', 'Molitor, T W']",,,,
,PMC,Congenital cardiac rhabdomyomas in red wattle pigs.,,PMC1686235,,,,,"McEwen, B J",,,,
,PMC,Translational Maintenance of Frame: Mutants of Saccharomyces Cerevisiae with Altered -1 Ribosomal Frameshifting Efficiences,,PMC1205794,,,"A special site on the (+) strand of the L-A dsRNA virus induces about 2% of ribosomes translating the gag open reading frame to execute a -1 frameshift and thus produce the viral gag-pol fusion protein. Using constructs in which a -1 ribosomal frameshift at this site was necessary for expression of lacZ we isolated chromosomal mutants in which the efficiency of frameshifting was increased. These mutants comprise eight genes, named mof (maintenance of frame). The mof1-1, mof2-1, mof4-1, mof5-1 and mof6-1 strains cannot maintain M(1) dsRNA at 30°, but, paradoxically, do not lose L-A. The mof2-1, mof5-1 and mof6-1 strains are temperature sensitive for growth at 37°, and all three show striking cell cycle phenotypes. The mof2-1 strains arrest with mother and daughter cells almost equal in size, mof5-1 arrests with multiple buds and mof6-1 arrests as single large unbudded cells. mof2-1 and mof5-1 strains are also Pet(-). The mof mutations show differential effects on various frameshifting signals.",,"['Dinman, J. D.', 'Wickner, R. B.']",,,,
,PMC,Expression of aminopeptidase-n (CD 13) in normal tissues and malignant neoplasms of epithelial and lymphoid origin.,,PMC501755,,,"AIMS--To provide a detailed knowledge of the distribution of the CD13 molecule, also known as the protease aminopeptidase-N, on both normal tissues and malignant neoplasms of epithelial and lymphoid origin. METHODS--CD13 antigen was examined by immunocytochemistry, using a recently produced antibody (VS5E) alongside a commercially available anti-CD13 monoclonal antibody. The VS5E recognising CD13 was produced by immunising a doxorubicin resistant breast cancer cell line (MCF-7-ADr). A striking feature of this antibody was that it stained the doxorubicin resistant cells but not the parental cell line. Both antibodies were tested on a broad range of normal tissues and three common types of epithelial malignancy (colon n = 28, lung n = 30, breast n = 35), and 12 cases of Hodgkin's and 52 of non-Hodgkin's lymphomas. RESULTS--CD13 was expressed on many tissue and cell types outside the haematopoietic system. In particular it was present on breast epithelium and in 20% (seven of 35) of breast carcinomas, but absent in normal and neoplastic colonic and bronchial tissues and lymphomas. CONCLUSIONS--This study provides not only detailed information about the expression of the CD13 antigen, but also raises the important possibility that CD13 expression may correlate with drug resistance in breast carcinomas.",,"['Dixon, J', 'Kaklamanis, L', 'Turley, H', 'Hickson, I D', 'Leek, R D', 'Harris, A L', 'Gatter, K C']",,,,
,PMC,Optimization of targeted RNA recombination and mapping of a novel nucleocapsid gene mutation in the coronavirus mouse hepatitis virus.,,PMC236292,,,"We have recently described a method of introducing site-specific mutations into the genome of the coronavirus mouse hepatitis virus (MHV) by RNA recombination between cotransfected genomic RNA and a synthetic subgenomic mRNA (C. A. Koetzner, M. M. Parker, C. S. Ricard, L. S. Sturman, and P. S. Masters, J. Virol. 66:1841-1848, 1992). By using a thermolabile N protein mutant of MHV (Alb4) as the recipient virus and synthetic RNA7 (the mRNA for the nucleocapsid protein N) as the donor, we selected engineered recombinant viruses as heat-stable progeny resulting from cotransfection. We have now been able to greatly increase the efficiency of targeted recombination in this process by using a synthetic defective interfering (DI) RNA in place of RNA7. The frequency of recombination is sufficiently high that, with Alb4 as the recipient, recombinants can be directly identified without using thermal selection. The synthetic DI RNA has been used to demonstrate that the lesion in another temperature-sensitive and thermolabile MHV mutant, Alb1, maps to the N gene. Sequencing of the Alb1 N gene revealed two closely linked point mutations that fall in a region of the N molecule previously noted as being the most highly conserved region among all of the coronavirus N proteins. Analysis of revertants of the Alb1 mutant revealed that one of the two mutations is critical for the temperature-sensitive phenotype; the second mutation is phenotypically silent.",,"['Masters, P S', 'Koetzner, C A', 'Kerr, C A', 'Heo, Y']",,,,
,PMC,Assembly of vaccinia virus: the second wrapping cisterna is derived from the trans Golgi network.,,PMC236272,,,"During the assembly of vaccinia virus, the intracellular mature virus becomes enwrapped by a cellular cisterna to form the intracellular enveloped virus (IEV), the precursor of the extracellular enveloped virus (EEV). In this study, we have characterized the origin of this wrapping cisterna by electron microscopic immunocytochemistry using lectins, antibodies against endocytic organelles, and recombinant vaccinia viruses expressing proteins which behave as Golgi resident proteins. No labelling for endocytic marker proteins could be detected on the wrapping membrane. However, the wrapping membrane labelled significantly for a trans Golgi network (TGN) marker protein. The recycling pathway from endosomes to the TGN appears to be greatly increased following vaccinia virus infection, since significant amounts of endocytic fluid-phase tracers were found in the lumen of the TGN, Golgi complex, and the wrapping cisternae. Using immunoelectron microscopy, we localized the vaccinia virus membrane proteins VV-p37, VV-p42, VV-p21, and VV-hemagglutinin (VV-HA) in large amounts in the wrapping cisternae, in the outer membranes of the IEV, and in the outermost membrane of the EEV. The bulk of the cellular VV-p37, VV-p21, and VV-p42 were in the TGN, whereas VV-HA was also found in large amounts on the plasma membrane and in endosomes. Collectively, these data argue that the TGN becomes enriched in vaccinia virus membrane proteins that facilitate the wrapping event responsible for the formation of the IEV.",,"['Schmelz, M', 'Sodeik, B', 'Ericsson, M', 'Wolffe, E J', 'Shida, H', 'Hiller, G', 'Griffiths, G']",,,,
,PMC,"Analysis of astrovirus serotype 1 RNA, identification of the viral RNA-dependent RNA polymerase motif, and expression of a viral structural protein.",,PMC236266,,,"We report the results from sequence analysis and expression studies of the gastroenteritis agent astrovirus serotype 1. We have cloned and sequenced 5,944 nucleotides (nt) of the estimated 7.2-kb RNA genome and have identified three open reading frames (ORFs). ORF-3, at the 3' end, is 2,361 nt in length and is fully encoded in both the genomic and subgenomic viral RNAs. Expression of ORF-3 in vitro yields an 87-kDa protein that is immunoprecipitated with a monoclonal antibody specific for viral capsids. This protein comigrates with an authentic 87-kDa astrovirus protein immunoprecipitated from infected cells, indicating that this region encodes a viral structural protein. The adjacent upstream ORF (ORF-2) is 1,557 nt in length and contains a viral RNA-dependent RNA polymerase motif. The viral RNA-dependent RNA polymerase motifs from four astrovirus serotypes are compared. Partial sequence (2,018 nt) of the most 5' ORF (ORF-1) reveals a 3C-like serine protease motif. The ORF-1 sequence is incomplete. These results indicate that the astrovirus genome is organized with nonstructural proteins encoded at the 5' end and structural proteins at the 3' end. ORF-2 has no start methionine and is in the -1 frame compared with ORF-1. We present sequence evidence for a ribosomal frameshift mechanism for expression of the viral polymerase.",,"['Lewis, T L', 'Greenberg, H B', 'Herrmann, J E', 'Smith, L S', 'Matsui, S M']",,,,
,PMC,Nonhomologous RNA recombination in tombusviruses: generation and evolution of defective interfering RNAs by stepwise deletions.,,PMC236259,,,"We used a protoplast system to study the mechanisms involved in the generation and evolution of defective interfering (DI) RNAs of tomato bushy stunt tombusvirus (TBSV). Synthetic transcripts corresponding to different naturally occurring TBSV DI RNAs, or to various artificially constructed TBSV defective RNAs, were analyzed. The relative levels of competitiveness of different DI RNAs were determined by coinoculating their corresponding transcripts into protoplasts along with helper genomic RNA transcripts and monitoring the level of DI RNA accumulation. Further studies were performed to assess the contribution of naked DI RNA stability and DI RNA encapsidation efficiency to the observed levels of competitiveness. In addition, the ability of various defective RNAs to evolve to alternative forms was tested by serially passaging protoplast infections initiated with transcripts corresponding to helper genomic RNA and a single type of defective RNA. These studies, and the analysis of the sequences of observed recombinants, indicate that (i) replication competence is a major factor dictating DI RNA competitiveness and is likely a primary determinant in DI RNA evolution, (ii) DI RNAs are capable of evolving to both smaller and larger forms, and the rates at which various transitions occur differ, (iii) DI RNA-DI RNA recombination and/or rearrangement is responsible for the formation of the evolved RNA molecules which were examined, and (iv) sequence complementarities between positive- and negative-sense strands in the regions of the junctions suggest that, in some cases, base pairing between an incomplete replicase-associated nascent strand and acceptor template may mediate selection of recombination sites. On the basis of our data, we propose a stepwise deletion model to describe the temporal order of events leading to the formation of tombusvirus DI RNAs.",,"['White, K A', 'Morris, T J']",,,,
,PMC,"Virus receptors: binding, adhesion strengthening, and changes in viral structure.",,PMC236257,,,,,"Haywood, A M",,,,
,PMC,An 'elaborated' pseudoknot is required for high frequency frameshifting during translation of HCV 229E polymerase mRNA.,,PMC310462,,,"The RNA polymerase gene (gene 1) of the human coronavirus 229E is approximately 20 kb in length and is located at the 5' end of the positive-strand genomic RNA. The coding sequence of gene 1 is divided into two large open reading frames, ORF1a and ORF1b, that overlap by 43 nucleotides. In the region of the ORF1a/ORF1b overlap, the genomic RNA displays two elements that are known to mediate (-1) ribosomal frameshifting. These are the slippery sequence, UUUAAAC, and a 3' pseudoknot structure. By introducing site-specific mutations into synthetic mRNAs, we have analysed the predicted structure of the HCV 229E pseudoknot and shown that besides the well-known stem structures, S1 and S2, a third stem structure, S3, is required for a high frequency of frameshifting. The requirement for an S3 stem is independent of the length of loop 2.",,"['Herold, J', 'Siddell, S G']",,,,
,PMC,CD4 cell surface downregulation in HIV-1 Nef transgenic mice is a consequence of intracellular sequestration.,,PMC413753,,,"The Nef gene product is a regulatory protein of HIV whose biological function is poorly understood. Nef has been thought to have a negative effect on viral replication in vitro but has been shown in studies with SIV to be necessary in the establishment of viraemia in vivo. In vitro studies in various human cell lines have shown that Nef downregulates the expression of cell surface CD4 and thus could have effects on the immune response. We have generated four transgenic mouse lines, with constructs containing two different Nef alleles under the control of CD2 regulatory elements to examine the interaction of Nef with the host immune system in vivo. In adult transgenic mice we have found marked downregulation in the level of CD4 on the surface of double positive thymocytes and a decrease in the number of CD4+ T cells in the thymus. Functional analyses have revealed a decrease in the total activation of transgenic thymocytes by anti-CD3 epsilon antibody. By specific intracellular staining of T cells in such mice we have found CD4 colocalizing with a Golgi-specific marker. These results strongly suggest a Nef mediated effect on developing CD4 thymocytes resulting from interference of Nef in the intracellular trafficking or post-translational modification of CD4.",,"['Brady, H J', 'Pennington, D J', 'Miles, C G', 'Dzierzak, E A']",,,,
,PMC,A translation-attenuating intraleader open reading frame is selected on coronavirus mRNAs during persistent infection.,,PMC48058,,,"Short open reading frames within the 5' leader of some eukaryotic mRNAs are known to regulate the rate of translation initiation on the downstream open reading frame. By employing the polymerase chain reaction, we learned that the 5'-terminal 5 nt on the common leader sequence of bovine coronavirus subgenomic mRNAs were heterogeneous and hypervariable throughout early infection in cell culture and that as a persistent infection became established, termini giving rise to a common 33-nt intraleader open reading frame were selected. Since the common leader is derived from the genomic 5' end during transcription, a common focus of origin for the heterogeneity is expected. The intraleader open reading frame was shown by in vitro translation studies to attenuate translation of downstream open reading frames in a cloned bovine coronavirus mRNA molecule. Selection of an intraleader open reading frame resulting in a general attenuation of mRNA translation and a consequent attenuation of virus replication may, therefore, be a mechanism by which coronaviruses and possibly other RNA viruses with a similar transcriptional strategy maintain a persistent infection.",,"['Hofmann, M A', 'Senanayake, S D', 'Brian, D A']",,,,
,PMC,Myelin basic protein-specific T lymphocyte repertoire in multiple sclerosis. Complexity of the response and dominance of nested epitopes due to recruitment of multiple T cell clones.,,PMC288460,,,"The human T cell response to the myelin basic protein (MBP) has been studied with respect to T cell receptor (TCR) usage, HLA class II restriction elements, and epitope specificity using a total of 215 long-term MBP-specific T cell lines (TCL) isolated from the peripheral blood of 13 patients with multiple sclerosis (MS) and 10 healthy donors. In most donors, the anti-MBP response was exceedingly heterogeneous. Using a panel of overlapping synthetic peptides spanning the entire length of human MBP, at least 26 epitopes recognized by human TCL could be distinguished. The MBP domain most commonly recognized was sequence 80-105 (31% of MS TCL, and 24% of control TCL). Sequence 29-48 was recognized more frequently by control-derived TCL (24%) than by TCL from MS patients (5%). The MBP epitopes were recognized in the context of DRB1 *0101, DRB5*0101, DRB1*1501, DRB1*0301, DRB1*0401, DRB1*1402, and DRB3*0102, as demonstrated using a panel of DR gene-transfected L cells. The TCR gene usage was also heterogeneous. V beta 5.2, a peptide of which is currently being used in a clinical trial for treatment of MS patients, was expressed by only one of our TCL. However, within this complex pattern of MBP-specific T cell responses, a minority of MS patients were found to exhibit a more restricted response with respect to their TCL epitope specificity. In these patients 75-87% of the TCL responded to a single, patient-specific cluster of immunodominant T cell epitopes located within a small (20-amino acid) domain of MBP. These nested clusters of immunodominant epitopes were noted within the amino acids 80-105, 108-131, and 131-153. The T cell response to the immunodominant epitopes was not monoclonal, but heterogeneous, with respect to fine specificity, TCR usage, and even HLA restriction. In one patient (H.K.), this restricted epitope profile remained stable for > 2 yr. The TCR beta chain sequences of TCL specific for the immunodominant region of HK are consistent with an oligoclonal response against the epitopes of this region (80-105). Further, two pairs of identical sequences were established from TCL generated from this patient at different times (June 1990 and June 1991), suggesting that some TCL specific for the immunodominant region persisted in the peripheral repertoire. The possible role of persistent immunodominant epitope clusters in the pathogenesis of MS remains to be established.",,"['Meinl, E', 'Weber, F', 'Drexler, K', 'Morelle, C', 'Ott, M', 'Saruhan-Direskeneli, G', 'Goebels, N', 'Ertl, B', 'Jechart, G', 'Giegerich, G']",,,,
,PMC,The cell surface receptor is a major determinant restricting the host range of the B-lymphotropic papovavirus.,,PMC238214,,,"The B-lymphotropic papovavirus (LPV) productively infects only a subset of human B-lymphoma-derived cell lines while transfection of the viral genome yields infectious viral particles in a much wider variety of human hematopoietic cell lines. We have analyzed the contribution of a putative LPV receptor on the cell surface of B-cell lines in restricting the virus host range. In order to establish a quantitative virus binding assay for LPV, infectious virus particles were highly purified by metrizamide equilibrium density centrifugation and used as immunogens to raise seven mouse monoclonal antibodies specific for LPV VP1. Virus particle binding was quantitated in an indirect, nonradioactive assay with an LPV VP1-specific enzyme-linked immunosorbent assay. Binding of LPV particles to permissive human B-lymphoma cell line BJA-B occurred within minutes. Kinetics and capacity of binding were similar at 4 and 37 degrees C. A BJA-B cell was estimated to bind approximately 600 virus particles at conditions under which 50% of the administered virus was bound. The sialidase and trypsin sensitivities of the cellular virus binding moiety show that sialylated and proteinaceous components are necessary components of the LPV receptor on BJA-B cells. Despite a high binding capacity of BJA-B cells for simian virus 40, LPV binding was not significantly affected by a 20-fold excess of simian virus 40 particles, indicating that these related polyomaviruses do not bind to the same receptor on BJA-B cells. Reduction of LPV binding to sialidase-pretreated BJA-B cells was accompanied by a similar reduction of infection, indicating that virus binding may be a limiting factor in the LPV replicative cycle. The two highly LPV-permissive human B-lymphoma cell lines BJA-B and Namalwa displayed high virus binding whereas low and nonpermissive hematopoietic cell lines showed reduced or undetectable virus binding. We conclude that the inability of LPV particles to productively infect the nonpermissive human hematopoietic cell lines analyzed is probably due to the absence or insufficient expression of a functional cell surface receptor.",,"['Haun, G', 'Keppler, O T', 'Bock, C T', 'Herrmann, M', 'Zentgraf, H', 'Pawlita, M']",,,,
,PMC,Disulfide bonds in folding and transport of mouse hepatitis coronavirus glycoproteins.,,PMC238203,,,"We have analyzed the effects of reducing conditions on the folding of the spike (S) protein and on the intracellular transport of the membrane (M) protein of the mouse hepatitis coronavirus. These proteins differ in their potential to form disulfide bonds in the lumen of the endoplasmic reticulum (ER). Intrachain disulfide bonds are formed in the S protein but not in M, which was demonstrated in a pulse-chase experiment by analyzing the viral proteins under nonreducing conditions. To reduce disulfide bonds in vivo, we added dithiothreitol (DTT) to the culture medium of mouse hepatitis coronavirus-infected cells following a procedure recently described by Braakman et al. (I. Braakman, J. Helenius, and A. Helenius, EMBO J. 11:1717-1722, 1992). Short exposure to DTT resulted in the complete reduction of newly synthesized S protein and affected its conformation as judged by the change in mobility in nonreducing gels and by the loss of recognition by a conformation-specific monoclonal antibody. Using this antibody in an immunofluorescence assay, we monitored the reducing effect of DTT in situ. DTT was found to initially affect only the S protein present in the ER; also, after longer treatment, the remaining signal also gradually disappeared. In contrast, folding and transport of the M protein were not inhibited by DTT. Under reducing conditions, M was transported efficiently to the trans side of the Golgi complex, indicating that cellular processes such as ER-to-Golgi transport, O-glycosylation, and Golgi retention were unaffected. In the presence of DTT, the M protein even moved at an increased rate to the Golgi complex, which is probably because of its failure to interact with unfolded S protein. The effects of in vivo reduction were reversible. When DTT was removed from pulse-labeled cells, the S protein folded posttranslationally and aberrantly; during its oxidation, most of S now transiently aggregated into large disulfide-linked complexes from which subsequently folded S molecules dissociated.",,"['Opstelten, D J', 'de Groote, P', 'Horzinek, M C', 'Vennema, H', 'Rottier, P J']",,,,
,PMC,Three different cellular proteins bind to complementary sites on the 5'-end-positive and 3'-end-negative strands of mouse hepatitis virus RNA.,,PMC238183,,,"The termini of viral genomic RNA and its complementary strand are important in the initiation of viral RNA replication, which probably involves both viral and cellular proteins. To detect the possible cellular proteins involved in the replication of mouse hepatitis virus RNA, we performed RNA-protein binding studies with RNAs representing both the 5' and 3' ends of the viral genomic RNA and the 3' end of the negative-strand complementary RNA. Gel-retardation assays showed that both the 5'-end-positive- and 3'-end-negative-strand RNA formed an RNA-protein complex with cellular proteins from the uninfected cells. UV cross-linking experiments further identified a 55-kDa protein bound to the 5' end of the positive-strand viral genomic RNA and two proteins 35 and 38 kDa in size bound to the 3' end of the negative-strand cRNA. The results of the competition assay confirmed the specificity of this RNA-protein binding. No proteins were found to bind to the 3' end of the viral genomic RNA under the same conditions. The binding site of the 55-kDa protein was mapped within the 56-nucleotide region from nucleotides 56 to 112 from the 5' end of the positive-strand RNA, and the 35- and 38-kDa proteins bound to the complementary region on the negative-strand RNA. The 38-kDa protein was detected only in DBT cells but was not detected in HeLa or COS cells, while the 35-kDa protein was found in all three cell types. The juxtaposition of the different cellular proteins on the complementary sites near the ends of the positive- and negative-strand RNAs suggests that these proteins may interact with each other and play a role in mouse hepatitis virus RNA replication.",,"['Furuya, T', 'Lai, M M']",,,,
,PMC,Characterization of mouse hepatitis virus-specific cytotoxic T cells derived from the central nervous system of mice infected with the JHM strain.,,PMC238166,,,"The cytotoxic T lymphocyte (CTL) activity of spleen cells from BALB/c (H-2d) mice immunized with the neurotropic JHM strain of mouse hepatitis virus (JHMV) was stimulated in vitro for 7 days. CTL were tested for recognition of target cells infected with either JHMV or vaccinia virus recombinants expressing the four virus structural proteins. Only target cells infected with either JHMV or the vaccinia virus recombinant expressing the JHMV nucleocapsid protein were recognized. Cytotoxic T cell lines were established by limiting dilution from the brains of mice undergoing acute demyelinating encephalomyelitis after infection with JHMV. Twenty of the 22 lines recognized JHMV-infected but not uninfected syngeneic target cells, indicating that they are specific for JHMV. All T-cell lines except one were CD8+. The specificity of the CTL lines was examined by using target cells infected with vaccinia virus recombinants expressing the JHMV nucleocapsid, spike, membrane, and hemagglutinin-esterase structural proteins. Seventeen lines recognized target cells expressing the nucleocapsid protein. Three of the JHMV-specific T-cell lines were unable to recognize target cells expressing any of the JHMV structural proteins, indicating that they are specific for an epitope of a nonstructural protein(s) of JHMV. These data indicate that the nucleocapsid protein induces an immunodominant CTL response. However, no CTL activity specific for the nucleocapsid protein could be detected in either the spleens or cervical lymph nodes of mice 4, 5, 6, or 7 days after intracranial infection, suggesting that the CTL response to JHMV infection within the central nervous system may be induced or expanded locally.",,"['Stohlman, S A', 'Kyuwa, S', 'Polo, J M', 'Brady, D', 'Lai, M M', 'Bergmann, C C']",,,,
,PMC,Characterization of the Ld-restricted cytotoxic T-lymphocyte epitope in the mouse hepatitis virus nucleocapsid protein.,,PMC238165,,,"The mouse hepatitis virus (MHV) JHM strain (JHMV) produces primary demyelination in the central nervous system associated with acute encephalomyelitis. Humoral and cellular immune responses both participate in controlling the development of chronic MHV-induced demyelination. A subset of the CD8+ cytotoxic T lymphocytes (CTL) induced by immunization of BALB/c (H-2d) mice with JHMV is specific for the viral nucleocapsid protein. This CTL population recognizes an epitope located within the carboxy-terminal 149 amino acids in association with the Ld class I molecule (S. A. Stohlman, S. Kyuwa, M. Cohen, C. Bergmann, J. P. Polo, J. Yeh, R. Anthony, and J. G. Keck, Virology 189:217-224, 1992). Using a panel of vaccinia virus recombinants expressing truncated forms of the nucleocapsid protein and a series of overlapping synthetic peptides, we mapped the response to 15 amino acids. This sequence, encompassing the MHV epitope, contains the Ld-specific binding motif. The predicted 9-mer peptide (residues 318 to 326: APTAGAFFF) was sufficient and highly active in sensitizing target cells for CTL recognition when either added exogenously or synthesized intracellularly. Cross-reactivity of JHMV nucleocapsid protein-specific CTL with six other MHV strains indicated that natural sequence variations within the 9-mer epitope are tolerated in positions 4 and 5, whereas all other amino acids are conserved. These data define a novel 9-mer Ld-restricted CTL epitope which represents the first MHV CTL epitope. Characterization of this epitope provides a molecular basis to study the role of nucleocapsid protein-specific CTL in the clearance of JHMV from the central nervous system.",,"['Bergmann, C', 'McMillan, M', 'Stohlman, S']",,,,
,PMC,Expression of virus-encoded proteinases: functional and structural similarities with cellular enzymes.,,PMC372939,,,"Many viruses express their genome, or part of their genome, initially as a polyprotein precursor that undergoes proteolytic processing. Molecular genetic analyses of viral gene expression have revealed that many of these processing events are mediated by virus-encoded proteinases. Biochemical activity studies and structural analyses of these viral enzymes reveal that they have remarkable similarities to cellular proteinases. However, the viral proteinases have evolved unique features that permit them to function in a cellular environment. In this article, the current status of plant and animal virus proteinases is described along with their role in the viral replication cycle. The reactions catalyzed by viral proteinases are not simple enzyme-substrate interactions; rather, the processing steps are highly regulated, are coordinated with other viral processes, and frequently involve the participation of other factors.",,"['Dougherty, W G', 'Semler, B L']",,,,
,PMC,Genetic stability and diversity of Pneumocystis carinii infecting rat colonies.,,PMC281237,,,"There is increasing molecular and antigenic evidence that Pneumocystis carinii organisms isolated from humans, ferrets, and rats are different species. In contrast, little is known about the extent of genetic diversity among P. carinii strains found within a single mammalian species. In the present study, electrophoretic karyotypes were obtained from P. carinii prepared from 10 chronically immunosuppressed rat colonies to investigate diversity at the chromosomal level. Most organism preparations produced patterns with 13 to 15 bands, but as many as 24 bands were observed in a few preparations. All bands separated between 700 and 300 kbp. Four distinct karyotype forms emerged from among the 13- to 15-band karyotypes of the 10 colonies sampled. Form 1 was shared by five rat strains from two vendors; form 2 was shared by two rat strains from the same vendor; and forms 3 and 4 were unique to their vendor colonies. Within a given rat colony, most rats harbored the same P. carinii karyotype. A survey of selected rat colonies showed that the karyotype within a vendor colony could remain stable over a period of 2 to 3 years. Hybridization of the blotted karyotypes with a repetitive DNA element isolated from rat-derived P. carinii and with single-copy gene probes showed that every chromosome in the karyotypes contained some repetitive DNA, and there was a general size concordance among the chromosomes carrying the unique gene loci. Differences in gene sequences, electrophoretic karyotypes, and hybridization profiles suggested that the immunosuppressed rats were infected by genetically distinct P. carinii strains. A provisional system of nomenclature for P. carinii that will permit differentiation of P. carinii organisms from the same mammalian host is discussed. These data show that all rats were not infected by a single type of P. carinii, that pulsed-field gradient electrophoresis can detect sufficient genetic diversity among the organism preparations to allow for characterization of the organisms, and that the genome of the organism within the rat host is relatively stable over time.",,"['Cushion, M T', 'Kaselis, M', 'Stringer, S L', 'Stringer, J R']",,,,
,PMC,Anti-idiotypic mimicry of a neutralizing epitope on the glycoprotein B complex of human cytomegalovirus.,,PMC238124,,,"Experiments were carried out to investigate the ability of rabbit anti-idiotype antibodies (Ab2), directed against an anti-human cytomegalovirus monoclonal antibody (Ab1), to induce neutralizing antibodies specific for the immunodominant glycoprotein B viral complex. Mice immunized with Ab2 produced anti-Ab2 (Ab3) that was both antigen and idiotype specific with regard to Ab1. We conclude that the Ab2 antibodies mimicked a neutralizing epitope and acted as a network antigen for inducing a specific anti-human cytomegalovirus antibody response in this experimental system.",,"['Tackaberry, E S', 'Hamel, J', 'Larose, Y', 'Brodeur, B R']",,,,
,PMC,CD13 (human aminopeptidase N) mediates human cytomegalovirus infection.,,PMC238095,,,"Human cytomegalovirus (HCMV) infects cells by a series of processes including attachment, penetration via fusion of the envelope with the plasma membrane, and transport of the viral DNA to the nucleus. The details of the early events of HCMV infection are poorly understood. We have recently reported that CD13, human aminopeptidase N, a metalloprotease, is present on blood cells susceptible in vitro to HCMV infection (C. Söderberg, S. Larsson, S. Bergstedt-Lindqvist, and E. Möller, J. Virol. 67:3166-3175, 1993). Here we report that human CD13 is involved in HCMV infection. Antibodies directed against human CD13 not only inhibit infection but also block binding of HCMV virions to susceptible cells. Compounds known to inhibit aminopeptidase activity block HCMV infection. HCMV-resistant murine fibroblasts have heightened susceptibility to HCMV infection after transfection with complementary DNA encoding human CD13. A significant increase in binding of HCMV was observed in the CD13-expressing transfectants compared with neomycin-resistant control mouse cells. However, murine fibroblasts transfected with mutant CD13, lacking a portion of the aminopeptidase active site, remained susceptible to HCMV infection. Thus, human CD13 appears to mediate HCMV infection by a process that increases binding, but its enzymatic domain is not necessary for infection.",,"['Söderberg, C', 'Giugni, T D', 'Zaia, J A', 'Larsson, S', 'Wahlberg, J M', 'Möller, E']",,,,
,PMC,Ribosomal pausing during translation of an RNA pseudoknot.,,PMC364755,,,"The genomic RNA of the coronavirus infectious bronchitis virus contains an efficient ribosomal frameshift signal which comprises a heptanucleotide slippery sequence followed by an RNA pseudoknot structure. The presence of the pseudoknot is essential for high-efficiency frameshifting, and it has been suggested that its function may be to slow or stall the ribosome in the vicinity of the slippery sequence. To test this possibility, we have studied translational elongation in vitro on mRNAs engineered to contain a well-defined pseudoknot-forming sequence. Insertion of the pseudoknot at a specific location within the influenza virus PB1 mRNA resulted in the production of a new translational intermediate corresponding to the size expected for ribosomal arrest at the pseudoknot. The appearance of this protein was transient, indicating that it was a true paused intermediate rather than a dead-end product, and mutational analysis confirmed that its appearance was dependent on the presence of a pseudoknot structure within the mRNA. These observations raise the possibility that a pause is required for the frameshift process. The extent of pausing at the pseudoknot was compared with that observed at a sequence designed to form a simple stem-loop structure with the same base pairs as the pseudoknot. This structure proved to be a less effective barrier to the elongating ribosome than the pseudoknot and in addition was unable to direct efficient ribosomal frameshifting, as would be expected if pausing plays an important role in frameshifting. However, the stem-loop was still able to induce significant pausing, and so this effect alone may be insufficient to account for the contribution of the pseudoknot to frameshifting.",,"['Somogyi, P', 'Jenner, A J', 'Brierley, I', 'Inglis, S C']",,,,
,PMC,Respiratory viruses and exacerbations of asthma in adults.,,PMC1679193,,,"OBJECTIVE--To study the role of respiratory viruses in exacerbations of asthma in adults. DESIGN--Longitudinal study of 138 adults with asthma. SETTING--Leicestershire Health Authority. SUBJECTS--48 men and 90 women 19-46 years of age with a mean duration of wheeze of 19.6 years. 75% received regular treatment with bronchodilators; 89% gave a history of eczema, hay fever, allergic rhinitis, nasal polyps, or allergies; 38% had been admitted to hospital with asthma. MAIN OUTCOME MEASURES--Symptomatic colds and asthma exacerbations; objective exacerbations of asthma with > or = 50 l/min reduction in mean peak expiratory flow rate when morning and night time readings on days 1-7 after onset of symptoms were compared with rates during an asymptomatic control period; laboratory confirmed respiratory tract infections. RESULTS--Colds were reported in 80% (223/280) of episodes with symptoms of wheeze, chest tightness, or breathlessness, and 89% (223/250) of colds were associated with asthma symptoms. 24% of 115 laboratory confirmed non-bacterial infections were associated with reductions in mean peak expiratory flow rate > or = 50 l/min through days 1-7 and 48% had mean decreases > or = 25 l/min. 44% of episodes with mean decreases in flow rate > or = 50 l/min were associated with laboratory confirmed infections. Infections with rhinoviruses, coronaviruses OC43 and 229E, influenza B, respiratory syncytial virus, parainfluenza virus, and chlamydia were all associated with objective evidence of an exacerbation of asthma. CONCLUSIONS--These findings show that asthma symptoms and reductions in peak flow are often associated with colds and respiratory viruses; respiratory virus infections commonly cause or are associated with exacerbations of asthma in adults.",,"['Nicholson, K G', 'Kent, J', 'Ireland, D C']",,,,
,PMC,8-aminoquinolines effective against Pneumocystis carinii in vitro and in vivo.,,PMC192245,,,"The activities of 25 8-aminoquinolines were compared in tests assessing the ability of the compounds to inhibit the growth of Pneumocystis carinii in culture. Six compounds were effective at or below 0.03 microM: CDRI 80/53, NSC19894, NSC305805, NSC305812, WR182234, and primaquine. Four others were effective at between 0.2 and 0.03 microM: NSC305835, WR225448, WR238605, and WR242511. Fourteen drugs were also tested in a standard model of P. carinii pneumonia in rats at daily doses of 2 mg/kg of body weight in drinking water. CDRI 80/53, NSC305805, NSC305835, and WR225448 were extremely effective in the animal model. The effectiveness of WR238605, WR242511, and primaquine in the rat model has been reported elsewhere (M. S. Bartlett, S. F. Queener, R. R. Tidwell, W. K. Milhouse, J. D. Berman, W. Y. Ellis, and J. W. Smith, Antimicrob. Agents Chemother. 35:277-282, 1991). The length of the alkyl chain separating the nitrogens in the substituent at position 8 of the quinoline ring was a strong determinant of anti-P. carinii activity.",,"['Queener, S F', 'Bartlett, M S', 'Nasr, M', 'Smith, J W']",,,,
,PMC,Impact of respiratory virus infection in patients with chronic chest disease.,,PMC2271374,,,"This study investigated the morbidity associated with respiratory virus infections in patients with well-documented chest disease, and the risk of transmission between close contacts. Patients informed the study team if they were exposed to a family member or colleague with a cold. Patients and symptomatic index cases recorded respiratory symptoms during the study period. Acute nasopharyngeal swabs and paired sera were obtained for viral diagnosis. Twenty-five (43%) of 58 recorded exposures resulted in a symptomatic illness and 16 (28%) patients developed lower respiratory tract symptoms. Sixteen (64%) of the 25 symptomatic patients contacted their general practitioner, 14 (56%) received antibiotics and 4 (16%) were hospitalized. Mean duration of illness was 10.6 days in symptomatic patients and 5.7 days in their corresponding index cases (P < 0.005). Mean symptom scores were 100.6 in symptomatic patients and 62.2 in index cases (P < 0.01). Respiratory viruses were identified in 19 (33%) episodes. Rhinovirus, coronavirus and respiratory syncytial virus infections were all associated with lower respiratory tract exacerbations. Respiratory tract symptoms following exposure to a cold were comparatively severe in these patients with chronic chest disease. This group of patients might gain particular benefit from the introduction of effective vaccines or antiviral therapy.",,"['Wiselka, M. J.', 'Kent, J.', 'Cookson, J. B.', 'Nicholson, K. G.']",,,,
,PMC,Two cis-acting signals control ribosomal frameshift between human T-cell leukemia virus type II gag and pro genes.,,PMC238052,,,"The open reading frame of the human T-cell leukemia virus type II pro gene is arranged at a -1 position relative to the gag gene. Synthesis of the Gag-Pro fusion polyprotein is facilitated by ribosomal frameshift into the reading frame of the pro gene. Cloning of a synthetic 41-bp oligonucleotide corresponding to the gag-pro junction within a heterologous gene (nef of human immunodeficiency virus type I) and mutation analysis revealed that two cis-acting signals, an adenosine residue stretch and a dyad symmetry sequence, flanking the UAA termination codon, are required for efficient ribosomal frameshifting between gag and pro. The stability of the stem-loop structure is crucial for frameshifting.",,"['Falk, H', 'Mador, N', 'Udi, R', 'Panet, A', 'Honigman, A']",,,,
,PMC,Deletion mapping of a mouse hepatitis virus defective interfering RNA reveals the requirement of an internal and discontiguous sequence for replication.,,PMC238033,,,"All of the defective interfering (DI) RNAs of mouse hepatitis virus (MHV) contain both the 5' and 3' ends of the viral genomic RNA, which presumably include the cis sequences required for RNA replication. To define the replication signal of MHV RNA, we have used a vaccinia virus-T7 polymerase-transcribed MHV DI RNA to study the effects of sequence deletion on DI RNA replication. Following infection of susceptible cells with a recombinant vaccinia virus expressing T7 RNA polymerase, various cDNA clones derived from a DI RNA (DIssF) of the JHM strain of MHV, which is a 3.5-kb naturally occurring DI RNA, behind a T7 promoter were transfected. On superinfection with a helper MHV, the ability of various DI RNAs to replicate was determined. Serial deletions from the middle of the RNA toward both the 5' and 3' ends demonstrated that 859 nucleotides from the 5' end and 436 nucleotides from the 3' end of the MHV RNA genome were necessary for RNA replication. Surprisingly, an additional stretch of 135 nucleotides located at 3.1 to 3.3 kb from the 5' end of the genome was also required. This stretch is discontiguous from the 5'-end cis replication signal and is present in all of the naturally occurring DI RNAs studied so far. The requirement for a long stretch of 5'- and 3'-end sequences predicts that the subgenomic MHV mRNAs cannot replicate. The efficiency of RNA replication varied with different cDNA constructs, suggesting possible interaction between different regions of DI RNA. The identification of MHV RNA replication signals allowed the construction of an MHV DI-based expression vector, which can express foreign genes, such as the chloramphenicol acetyltransferase gene.",,"['Lin, Y J', 'Lai, M M']",,,,
,PMC,Identification of the catalytic sites of a papain-like cysteine proteinase of murine coronavirus.,,PMC238026,,,"The murine coronavirus mouse hepatitis virus gene 1 is expressed as a polyprotein, which is cleaved into multiple proteins posttranslationally. One of the proteins is p28, which represents the amino-terminal portion of the polyprotein and is presumably generated by the activity of an autoproteinase domain of the polyprotein (S. C. Baker, C. K. Shieh, L. H. Soe, M.-F. Chang, D. M. Vannier, and M. M. C. Lai, J. Virol. 63:3693-3699, 1989). In this study, the boundaries and the critical amino acid residues of this putative proteinase domain were characterized by deletion analysis and site-directed mutagenesis. Proteinase activity was monitored by examining the generation of p28 during in vitro translation in rabbit reticulocyte lysates. Deletion analysis defined the proteinase domain to be within the sequences encoded from the 3.6- to 4.4-kb region from the 5' end of the genome. A 0.7-kb region between the substrate (p28) and proteinase domain could be deleted without affecting the proteolytic cleavage. However, a larger deletion (1.6 kb) resulted in the loss of proteinase activity, suggesting the importance of spacing sequences between proteinase and substrate. Computer-assisted analysis of the amino acid sequence of the proteinase domain identified potential catalytic cysteine and histidine residues in a stretch of sequence distantly related to papain-like cysteine proteinases. The role of these putative catalytic residues in the proteinase activity was studied by site-specific mutagenesis. Mutations of Cys-1137 or His-1288 led to a complete loss of proteinase activity, implicating these residues as essential for the catalytic activity. In contrast, most mutations of His-1317 or Cys-1172 had no or only minor effects on proteinase activity. This study establishes that mouse hepatitis virus gene 1 encodes a proteinase domain, in the region from 3.6 to 4.4 kb from the 5' end of the genome, which resembles members of the papain family of cysteine proteinases and that this proteinase domain is responsible for the cleavage of the N-terminal peptide.",,"['Baker, S C', 'Yokomori, K', 'Dong, S', 'Carlisle, R', 'Gorbalenya, A E', 'Koonin, E V', 'Lai, M M']",,,,
,PMC,Spontaneous mutagenesis of a plant potyvirus genome after insertion of a foreign gene.,,PMC238018,,,"The RNA genome of tobacco etch potyvirus (TEV) was engineered to express bacterial beta-glucuronidase (GUS) fused to the virus helper component proteinase (HC-Pro). It was shown previously that prolonged periods (approximately 1 month) of TEV-GUS propagation in plants resulted in the appearance of spontaneous deletion variants. Nine deletion mutants were identified by nucleotide sequence analysis of 40 cDNA clones obtained after polymerase chain reaction amplification. The mutants were missing between 1,741 and 2,074 nucleotides from TEV-GUS, including the sequences coding for most of GUS and the N-terminal region of HC-Pro. This region of HC-Pro contains determinants involved in helper component activity during aphid transmission, as well as a highly conserved series of cysteine residues. The deletion variants were shown to replicate and move systemically without the aid of a helper virus. Infectious viruses harboring the two largest HC-Pro deletions (termed TEV-2del and TEV-7del) were reconstructed by subcloning the corresponding mutated regions into full-length DNA copies of the TEV genome. Characterization of these and additional variants derived by site-directed mutagenesis demonstrated that deletion of sequences coding for the HC-Pro N-terminal domain had a negative effect on accumulation of viral RNA and coat protein. The TEV-2del variant possessed an aphid-nontransmissible phenotype that could be rescued partially by prefeeding of aphids on active HC-Pro from another potyvirus. These data suggest that the N-terminal domain of HC-Pro or its coding sequence enhances virus replication or genome expression but does not provide an activity essential for these processes. The function of this domain, as well as a proposed deletion mechanism involving nonhomologous recombination, is discussed.",,"['Dolja, V V', 'Herndon, K L', 'Pirone, T P', 'Carrington, J C']",,,,
,PMC,"ADA3: a gene, identified by resistance to GAL4-VP16, with properties similar to and different from those of ADA2.",,PMC364647,,,"We describe the isolation of a yeast gene, ADA3, mutations in which prevent the toxicity of GAL4-VP16 in vivo. Toxicity was previously proposed to be due to the trapping of general transcription factors required at RNA polymerase II promoters (S. L. Berger, B. Piña, N. Silverman, G. A. Marcus, J. Agapite, J. L. Regier, S. J. Triezenberg, and L. Guarente, Cell 70:251-265, 1992). trans activation by VP16 as well as the acidic activation domain of GCN4 is reduced in the mutant. Other activation domains, such as those of GAL4 and HAP4, are only slightly affected in the mutant. This spectrum is similar to that observed for mutants with lesions in ADA2, a gene proposed to encode a transcriptional adaptor. The ADA3 gene is not absolutely essential for cell growth, but gene disruption mutants grow slowly and are temperature sensitive. Strains doubly disrupted for ada2 and ada3 grow no more slowly than single mutants, providing further evidence that these genes function in the same pathway. Selection of initiation sites by the general transcriptional machinery in vitro is altered in the ada3 mutant, providing a clue that ADA3 could be a novel general transcription factor involved in the response to acidic activators.",,"['Piña, B', 'Berger, S', 'Marcus, G A', 'Silverman, N', 'Agapite, J', 'Guarente, L']",,,,
,PMC,Proceedings of the British Thoracic Society,,PMC464852,,,,,,,,,
,PMC,Minerva,,PMC1679006,,,,,,,,,
,PMC,"Smoking, alcohol consumption, and susceptibility to the common cold.",,PMC1694990,,,"OBJECTIVES. This study was conducted to test the supposition that both smoking and consuming alcohol suppress host resistance to viral infections. METHODS. The relations between smoking, alcohol consumption, and the incidence of documented clinical colds were prospectively studied among 391 subjects intentionally exposed to one of five respiratory viruses and 26 subjects given saline. Clinical colds were defined as clinical symptoms verified by the isolation of virus or by an increase in virus-specific antibody titer. Analyses included control variables for demographics; body weight; virus; and environmental, immunological and psychological factors. RESULTS. Smokers were at greater risk for developing colds than nonsmokers because smokers were more likely both to develop infections and to develop illness following infection. Greater numbers of alcoholic drinks (up to three or four per day) were associated with decreased risk for developing colds because drinking was associated with decreased illness following infection. However, the benefits of drinking occurred only among nonsmokers. CONCLUSIONS. Susceptibility to colds was increased by smoking. Although alcohol consumption did not influence risk of clinical illness for smokers, moderate alcohol consumption was associated with decreased risk for nonsmokers.",,"['Cohen, S', 'Tyrrell, D A', 'Russell, M A', 'Jarvis, M J', 'Smith, A P']",,,,
,PMC,T cell memory specific for self and non-self antigens in rats persistently infected with Borna disease virus.,,PMC1554921,,,"We have studied CD4+ Th1 T cell responses in Borna disease (BD), a virus-mediated immune disease of the central nervous system (CNS), and demonstrate the priming of virus-specific as well as autoreactive T cells specific for myelin antigens in the course of viral infection. The fate of these in vivo generated T cells was subsequently assessed by in vitro proliferation assays with lymphocytes from different lymphoid organs of diseased animals over a long period of time. Virus-specific T cell responses continuously decreased during the establishment of persistent infection and could no longer be detected after 5-6 months post infectionem, when inflammatory reactions in the brain had ceased. By contrast, autoantigen-specific T cells kept their ability to mount characteristic secondary responses--although at an overall rather low level--over long periods of time; these autoreactive T cells homed to a specific lymphoid organ, the perithymic lymph node. Our study thus describes for the first time a complete decline of virus-specific T cell memory in a persistent viral infection, and raises the question how long-lasting T cell autoreactivity is controlled.",,"['Rott, O', 'Herzog, S', 'Cash, E']",,,,
,PMC,A heptanucleotide sequence mediates ribosomal frameshifting in mammalian cells.,,PMC237961,,,"Ribosomal frameshifting is an essential requirement for replication of many viruses and retrovirus-like elements. It is regarded as a potential target for antiretroviral therapy. It has been shown that the frameshifting event takes place in the -1 direction within a sequence, the slippery sequence, which is usually followed by structured RNA. To distinguish between the basic sequence requirements and the modulating elements in intact cells, we have established a sensitive assay system for quantitative determination of ribosomal frameshifting in mammalian cell culture. In this assay system, the gag and pol genes of human immunodeficiency virus type 1 are replaced by the genes for the functional enzymes beta-galactosidase and luciferase, respectively. The sensitivity of the test system allows us to demonstrate for the first time that the slippery sequence, a heptanucleotide, is sufficient to mediate a basal level of ribosomal frameshifting independent of its position within a gene. The stem-loop sequence serves only as a positive modulator. These data indicate that frameshifting could also occur during translation of cellular genes in which a slippery sequence is present within the reading frame. The resulting putative transframe proteins might have a functional importance for cellular processes.",,"['Reil, H', 'Kollmus, H', 'Weidle, U H', 'Hauser, H']",,,,
,PMC,Sindbis virus membrane fusion is mediated by reduction of glycoprotein disulfide bridges at the cell surface.,,PMC237952,,,"We have examined the role of thiol-disulfide exchange reactions during the penetration of cells by Sindbis virus. The protein-protein association that form the rigid icosahedral lattice of the Sindbis virus envelope have been shown to be stabilized by disulfide bridges, and reduction of these critical disulfide bridges during cell penetration may be the mechanism by which the rigid protein lattice is disrupted prior to fusion (R. Anthony and D. T. Brown, J. Virol. 65:1187-1194, 1991; R. Anthony, A. Paredes, and D. T. Brown, Virology 190:330-336, 1992). Reduction of disulfide bridges occurs at near neutral pHs via thiol-disulfide exchange reactions, and these reactions can be blocked by covalent modification of the thiol involved. In this study, the effects of the reducing agent 2-mercaptoethanol on Sindbis virus-mediated cell-cell fusion from without and the effects of the membrane-impermeable thiol-alkylating reagent 5,5'-dithiobis(2-nitrobenzoic acid) on Sindbis virus penetration were determined. The presence of exogenous reducing agent was found to induce fusion from without under conditions unfavorable to both typical Sindbis virus-mediated fusion from without and cysteine-mediated thiol-disulfide exchange reactions. In addition, the thiol-alkylating reagent was found to inhibit Sindbis virus entry when present during infection. These results are consistent with a model for Sindbis virus entry in which reduction of critical disulfide bridges at the cell surface disrupts the rigid protein-protein associations of the envelope, allowing membrane fusion and release of the viral genome into the cell.",,"['Abell, B A', 'Brown, D T']",,,,
,PMC,Inhibition of African swine fever virus binding and infectivity by purified recombinant virus attachment protein p12.,,PMC237948,,,"The African swine fever virus protein p12, involved in virus attachment to the host cell, has an apparent molecular mass of 17 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions. We have also identified 12- and 10-kDa forms of the p12 protein in infected Vero cells and found that the mature 17-kDa protein is the only form present in virus particles. The p12 protein has been produced in large amounts in Spodoptera frugiperda insect cells infected with a recombinant baculovirus. A 17-kDa protein that possessed the biological properties of the viral protein was produced, since it bound to susceptible Vero cells and not to receptor-negative L cells, which do not support virus replication. The binding of the baculovirus-expressed protein p12 to Vero cells was specifically blocked by virus particles. In addition, the recombinant protein purified by immunoaffinity chromatography blocked the specific binding of virus particles to susceptible cells and prevented infection, demonstrating that the p12 protein mediates the attachment of virions to specific receptors and indicating that blocking the p12-mediated interaction between African swine fever virus and receptors in Vero cells can inhibit infection. However, although antibodies specific for protein p12 are induced in natural infections and in animals inoculated with inactivated virus or recombinant protein p12, these antisera did not inhibit virus binding to the host cell or neutralize virus infectivity.",,"['Angulo, A', 'Viñuela, E', 'Alcamí, A']",,,,
,PMC,Glycoprotein E1 of hog cholera virus expressed in insect cells protects swine from hog cholera.,,PMC237945,,,"The processing and protective capacity of E1, an envelope glycoprotein of hog cholera virus (HCV), were investigated after expression of different versions of the protein in insect cells by using a baculovirus vector. Recombinant virus BacE1[+] expressed E1, including its C-terminal transmembrane region (TMR), and generated a protein which was similar in size (51 to 54 kDa) to the size of E1 expressed in swine kidney cells infected with HCV. The protein was not secreted from the insect cells, and like wild-type E1, it remained sensitive to endo-beta-N-acetyl-D-glucosaminidase H (endo H). This indicates that E1 with a TMR accumulates in the endoplasmic reticulum or cis-Golgi region of the cell. In contrast, recombinant virus BacE1[-], which expressed E1 without a C-terminal TMR, generated a protein that was secreted from the cells. The fraction of this protein that was found to be cell associated had a slightly lower molecular mass (49 to 52 kDa) than wild-type E1 and remained endo H sensitive. The high-mannose units of the secreted protein were trimmed during transport through the exocytotic pathway to endo H-resistant glycans, resulting in a protein with a lower molecular mass (46 to 48 kDa). Secreted E1 accumulated in the medium to about 30 micrograms/10(6) cells. This amount was about 3-fold higher than that of cell-associated E1 in BacE1[-] and 10-fold higher than that of cell-associated E1 in BacE1[+]-infected Sf21 cells. Intramuscular vaccination of pigs with immunoaffinity-purified E1 in a double water-oil emulsion elicited high titers of neutralizing antibodies between 2 and 4 weeks after vaccination at the lowest dose tested (20 micrograms). The vaccinated pigs were completely protected against intranasal challenge with 100 50% lethal doses of HCV strain Brescia, indicating that E1 expressed in insect cells is an excellent candidate for development of a new, safe, and effective HCV subunit vaccine.",,"['Hulst, M M', 'Westra, D F', 'Wensvoort, G', 'Moormann, R J']",,,,
,PMC,Herpes simplex virus type 1 and pseudorabies virus bind to a common saturable receptor on Vero cells that is not heparan sulfate.,,PMC237906,,,"Herpes simplex virus type 1 (HSV-1) and pseudorabies virus (PRV) infect different natural hosts but are very similar in structure, replicative cycle, and entry into cultured cells. We determined whether HSV-1 and PRV use the same cellular components during entry into Vero cells, which are highly susceptible to each virus but are not from native hosts for either. UV-inactivated virions of either HSV-1 or PRV could saturate cell surfaces to block infection of challenge HSV-1 or PRV. In the presence of saturating levels for infection of either virus, radiolabeled virus bound well and in a heparin-sensitive manner. This result shows that heparan sulfate proteoglycans on Vero cells are not the limiting cellular component. To identify the virus component required for blocking, we used an HSV-1 null mutant virus lacking gB, gD, or gH as blocking virus. Virions lacking gB were able to block infection of challenge virus to the same level as did virus containing gB. In contrast, virions lacking gD lost all and most of the ability to block infection of HSV-1 and PRV, respectively. HSV-1 lacking gH and PRV lacking gp50 also were less competent in blocking infection of challenge virus. We conclude that HSV-1 and PRV bind to a common receptor for infection of Vero cells. Although both viruses bind a heparin-like cell component on many cells, including Vero cells, they also attach to a different and limited cell surface component that is bound at least by HSV-1 gD and possibly gH and to some degree by PRV gp50 but not gB. These results clearly demonstrate binding of both HSV-1 and PRV to a common cell receptor that is not heparan sulfate and demonstrate that several types of attachment occur for both viruses during infectious entry.",,"['Lee, W C', 'Fuller, A O']",,,,
,PMC,Signs and symptoms in common colds.,,PMC2271186,,,"The patterns of disease caused by five common viruses which infect the respiratory tract are described. The viruses were strains of rhinovirus types 2, 9, and 14, a strain of coronavirus type 229E and of respiratory syncytial virus. Volunteers were given nasal drops containing a low infectious dose of one of the viruses, quarantined from 2 days before to 5 days after inoculation, and examined daily by a clinician using a standard checklist of respiratory signs and symptoms. Only subjects who developed clinical illness accompanied by viral shedding and/or specific antibody production were analysed [n = 116]. The results confirm indication from earlier studies that the main difference between colds induced by different viruses is in duration of the incubation period. Patterns of symptom development were not substantially different with different viruses. Analyses of signs and symptoms in different categories, e.g. nasal symptoms v. coughing, justify treatment with different drugs either successively or simultaneously.",,"['Tyrrell, D. A.', 'Cohen, S.', 'Schlarb, J. E.']",,,,
,PMC,Secretory protein traffic. Chromogranin A contains a dominant targeting signal for the regulated pathway.,,PMC294945,,,"Secretory proteins are targeted into either constitutive (secreted upon synthesis) or regulated (stored in vesicles and released in response to a secretagogue) pathways. To investigate mechanisms of protein targeting into catecholamine storage vesicles (CSV), we stably expressed human chromogranin A (CgA), the major soluble protein in human CSV, in the rat pheochromocytoma PC-12 cell line. Chromaffin cell secretagogues (0.1 mM nicotinic cholinergic agonist, 55 mM K+, or 2 mM Ba++) caused cosecretion of human CgA and catecholamines from human CgA-expressing cells. Sucrose gradients colocalized human CgA and catecholamines to subcellular particles of the same buoyant density. Chimeric proteins, in which human CgA (either full-length [457 amino acids] or truncated [amino-terminal 226 amino acids]) was fused in-frame to the ordinarily nonsecreted protein chloramphenicol acetyltransferase (CAT), were expressed transiently in PC-12 cells. Both constructs directed CAT activity into regulated secretory vesicles, as judged by secretagogue-stimulated release. These data demonstrate that human CgA expressed in PC-12 cells is targeted to regulated secretory vesicles. In addition, human CgA can divert an ordinarily non-secreted protein into the regulated secretory pathway, consistent with the operation of a dominant targeting signal for the regulated pathway within the peptide sequence of CgA.",,"['Parmer, R J', 'Xi, X P', 'Wu, H J', 'Helman, L J', 'Petz, L N']",,,,
,PMC,The signal for translational readthrough of a UGA codon in Sindbis virus RNA involves a single cytidine residue immediately downstream of the termination codon.,,PMC237898,,,"The nucleotide sequences surrounding termination codons influence the efficiency of translational readthrough. In this report, we examined the sequence requirement for efficient readthrough of the UGA codon in the Sindbis virus genomic RNA which regulates production of the putative viral RNA polymerase, nsP4. The UGA codon and its neighboring nucleotide sequences were subcloned into a heterologous coding context, and readthrough efficiency was measured by cell-free translation of RNA transcripts in rabbit reticulocyte lysates. The CUA codon immediately downstream of the UGA codon was found to be sufficient for efficient translational readthrough. Further mutagenesis of residues in the CUA triplet demonstrated that mutations at the second or third residues following the UGA codon (U and A, respectively) had little effect on readthrough efficiency. In contrast, replacement of the cytidine residue immediately downstream of the UGA codon with any of the other three nucleotides (U, A, or G) dramatically reduced the readthrough efficiency from approximately 10% to less than 1%. These results show that a simple sequence context can allow efficient readthrough of UGA codons in a mammalian translation system. Interestingly, compilation studies of nucleotide sequences surrounding eukaryotic termination codons indicate a strong bias against cytidine residues immediately 3' to UGA termination codons. Taken together with our results, this bias may reflect a selective pressure for efficient translation termination for most eukaryotic gene products.",,"['Li, G', 'Rice, C M']",,,,
,PMC,Human immunodeficiency virus type 1 Vpu protein is an oligomeric type I integral membrane protein.,,PMC237897,,,"The human immunodeficiency virus type 1 Vpu protein is a 16-kDa phosphoprotein which enhances the efficiency of virion production and induces rapid degradation of CD4, the cellular receptor for human immunodeficiency virus. The topology of membrane-inserted Vpu was investigated by using in vitro-synthesized Vpu cotranslationally inserted into canine microsomal membranes. Proteolytic digestion and immunoprecipitation studies revealed that Vpu was a type I integral membrane protein, with the hydrophilic domain projecting from the cytoplasmic membrane face. In addition, several high-molecular-weight proteins containing Vpu were identified by chemical cross-linking. Such complexes also formed when wild-type Vpu and a Tat-Vpu fusion protein were coexpressed. Subsequent analysis by one- and two-dimensional electrophoresis revealed that these high-molecular-weight complexes consisted of homo-oligomers of Vpu. These findings indicate that Vpu is a type I integral membrane protein capable of multimerization.",,"['Maldarelli, F', 'Chen, M Y', 'Willey, R L', 'Strebel, K']",,,,
,PMC,In vivo role of lymphocyte subpopulations in the control of virus excretion and mucosal antibody responses of cattle infected with rotavirus.,,PMC237889,,,"T-cell control of primary rotavirus infection and mucosal antibody responses to rotavirus was studied with monoclonal antibodies (MAb) to deplete gnotobiotic calves of CD4+, CD8+, BoWC1+, or both CD4+ and CD8+ lymphocytes prior to infection with rotavirus. Injection of these MAb produced specific reductions in circulating and tissue lymphocyte subpopulations. Following infection, control calves developed fecal immunoglobulin M (IgM) and IgA antibodies and serum IgM and IgG1 antibodies; there was no IgG2 antibody produced. Anti-CD4-treated calves had reduced fecal and serum antibody responses to rotavirus compared with control calves. The IgM response was less affected than the other isotypes. Calves concurrently injected with MAb to CD4 and CD8 had antibody responses similar to those of calves injected with anti-CD4 antibody alone. No effect on serum or fecal antibody levels was seen when MAb to CD8 or BoWC1 were injected alone. Virus excretion was significantly increased in calves depleted of CD8+ cells. Depletion of CD4+ cells or BoWC1+ cells had no effect on virus excretion. Calves depleted of both CD4+ and CD8+ cells excreted amounts of virus similar to those of calves depleted of CD8+ cells alone. Onset and duration of virus excretion were not affected by any of the MAb treatments. We conclude that a CD8+ cell population is involved in limiting primary rotavirus infection, while CD4+ or BoWC1+ (gamma/delta+ TcR) lymphocytes are not. Furthermore, CD4+ lymphocytes (but not CD8+ or BoWC1+ lymphocytes) were shown to be important in the generation of mucosal, as well as systemic, antibody responses.",,"['Oldham, G', 'Bridger, J C', 'Howard, C J', 'Parsons, K R']",,,,
,PMC,RNA structure and heterologous recombination in the double-stranded RNA bacteriophage phi 6.,,PMC237879,,,"Bacteriophage phi 6 has a genome of three segments of double-stranded RNA, designated L, M, and S. A 1.2-kbp kanamycin resistance gene was inserted into segment M but was shown to be genetically unstable because of a high recombination rate between segment M and the 3' ends of segments S and L. The high rate of recombination is due to complementary homopolymer tracts bounding the kan gene. Removal of one arm of this potential hairpin stabilizes the insertion. The insertion of a 241- or 427-bp lacZ' gene into segment M leads to a stable Lac+ phage. The insertion of the same genes bounded by complementary homopolymer arms leads to recombinational instability. A stable derivative of this phage was shown to have lost one of the homopolymer arms. Several other conditions foster recombination. The truncation of a genomic segment at the 3' end prevents replication, but such a damaged molecule can be rescued by recombination. Similarly, insertion of the entire 3-kb lacZ gene prevents normal formation of virus, but the viral genes can be rescued by recombination. It appears that conditions leading to the retardation or absence of replication of a particular genomic segment facilitate recombinational rescue.",,"['Onodera, S', 'Qiao, X', 'Gottlieb, P', 'Strassman, J', 'Frilander, M', 'Mindich, L']",,,,
,PMC,Effects of deletions in the carboxy-terminal hydrophobic region of herpes simplex virus glycoprotein gB on intracellular transport and membrane anchoring.,,PMC237873,,,"The gB glycoprotein of herpes simplex virus type 1 is involved in viral entry and fusion and contains a predicted membrane-anchoring sequence of 69 hydrophobic amino acids, which can span the membrane three times, near the carboxy terminus. To define the membrane-anchoring sequence and the role of this hydrophobic stretch, we have constructed deletion mutants of gB-1, lacking one, two, or three predicted membrane-spanning segments within the 69 amino acids. Expression of the wild-type and mutant glycoproteins in COS-1 cells show that mutant glycoproteins lacking segment 3 (amino acids 774 to 795 of the gB-1 protein) were secreted from the cells. Protease digestion and alkaline extraction of microsomes containing labeled mutant proteins further showed that segment 3 was sufficient for stable membrane anchoring of the glycoproteins, indicating that this segment may specify the transmembrane domain of the gB glycoprotein. Also, the mutant glycoproteins containing segment 3 were localized in the nuclear envelop, which is the site of virus budding. Deletion of any of the hydrophobic segments, however, affected the intracellular transport and processing of the mutant glycoproteins. The mutant glycoproteins, although localized in the nuclear envelope, failed to complement the gB-null virus (K082). These results suggest that the carboxy-terminal hydrophobic region contains essential structural determinants of the functional gB glycoprotein.",,"['Rasile, L', 'Ghosh, K', 'Raviprakash, K', 'Ghosh, H P']",,,,
,PMC,MxA-dependent inhibition of measles virus glycoprotein synthesis in a stably transfected human monocytic cell line.,,PMC237862,,,"The alpha/beta (type I) interferon-inducible human MxA protein confers resistance to vesicular stomatitis virus (VSV) and influenza A virus in MxA-transfected mouse 3T3 cells (3T3/MxA). We investigated the inhibitory effects of the MxA protein on measles virus (MV) and VSV in the human monocytic cell line U937. In transfected U937 clones which constitutively express MxA (U937/MxA), the release of infectious MV and VSV was reduced approximately 100-fold in comparison with control titers. Transcription of VSV was inhibited similar to that observed for 3T3/MxA cells, whereas no difference was detected for MV in the rates of transcription or the levels of MV-specific mRNAs. In contrast, analysis of MV protein expression by immunofluorescence and immunoprecipitation revealed a significant reduction in the synthesis of MV glycoproteins F and H in U937/MxA cells. These data demonstrate a virus-specific effect of MxA which may, in the case of MV, contribute to the establishment of a persistent infection in human monocytic cells.",,"['Schnorr, J J', 'Schneider-Schaulies, S', 'Simon-Jödicke, A', 'Pavlovic, J', 'Horisberger, M A', 'ter Meulen, V']",,,,
,PMC,Fusion-defective mutants of mouse hepatitis virus A59 contain a mutation in the spike protein cleavage signal.,,PMC237834,,,"Infection of primary mouse glial cell cultures with mouse hepatitis virus strain A59 results in a productive, persistent infection, but without any obvious cytopathic effect. Mutant viruses isolated from infected glial cultures 16 to 18 weeks postinfection replicate with kinetics similar to those of wild-type virus but produce small plaques on fibroblasts and cause only minimal levels of cell-to-cell fusion under conditions in which wild type causes nearly complete cell fusion. However, since extensive fusion is present in mutant-infected cells at late times postinfection, the defect is actually a delay in kinetics rather than an absolute block in activity. Addition of trypsin to mutant-infected fibroblast cultures enhanced cell fusion a small (two- to fivefold) but significant degree, indicating that the defect could be due to a lack of cleavage of the viral spike (fusion) protein. Sequencing of portions of the spike genes of six fusion-defective mutants revealed that all contained the same single nucleotide mutation resulting in a substitution of aspartic acid for histidine in the spike cleavage signal. Mutant virions contained only the 180-kDa form of spike protein, suggesting that this mutation prevented the normal proteolytic cleavage of the 180-kDa protein into the 90-kDa subunits. Examination of revertants of the mutants supports this hypothesis. Acquisition of fusion competence correlates with the replacement of the negatively charged aspartic acid with either the wild-type histidine or a nonpolar amino acid and the restoration of spike protein cleavage. These data confirm and extend previous reports concluding cleavage of S is required for efficient cell-cell fusion by mouse hepatitis virus but not for virus-cell fusion (infectivity).",,"['Gombold, J L', 'Hingley, S T', 'Weiss, S R']",,,,
,PMC,Targeting the site of RNA-RNA recombination in brome mosaic virus with antisense sequences.,,PMC46937,,,"It has been postulated that local hybridizations between viral RNAs can mediate recombination in brome mosaic virus (BMV) and in poliovirus. To test this model, a 3' fragment of BMV RNA1 was inserted into the 3' noncoding sequence of BMV RNA3 in an antisense orientation. This resulted in high-frequency nonhomologous crossovers at or near the hybridized region. Insertion of the same RNA1 fragment in a positive-sense orientation did not promote recombination. Modification of the antisense insert by deletion of 3' portions did not affect the sites of crossover. However, modification of the 5' portion shifted the crossovers toward the central part of the heteroduplex region. Our results provide experimental evidence that recombinant crosses can be primed by hybridization between viral RNA molecules.",,"['Nagy, P D', 'Bujarski, J J']",,,,
,PMC,Determination of lactose and xylose malabsorption in preruminant diarrheic calves.,,PMC1263616,,,"In preliminary studies feeding the poorly absorbed carbohydrate sorbitol at 2.3 g/kg body weight as an indication of maximal fermentative capacity failed to produce the expected large increase in breath hydrogen excretion but did produce a transient diarrhea in five out of six control calves. Twelve healthy control and eighteen diarrheic calves were fed lactose or D-xylose on consecutive days at 1.15 g/kg body weight and a concentration of 46 g/L. Breath and blood samples were collected at 1 h intervals from 0 to 7 h. After administration of lactose, there was a significant increase in breath hydrogen excretion in diarrheic versus control calves. The increase in plasma glucose concentrations was delayed in diarrheic calves but the area under the absorption curve was similar in control and diarrheic calves. After administration of D-xylose, breath hydrogen excretion did not increase significantly but plasma D-xylose concentrations were significantly reduced in diarrheic calves. The pathogens commonly isolated from the feces were Cryptosporidium species, rotavirus and coronavirus. The number of pathogens and the severity of the calves' acid-base deficit were not related to the severity of carbohydrate malabsorption. Decreased absorption of lactose and D-xylose may be the result of intestinal villous atrophy caused by viral or parasite infection. It was concluded that carbohydrate malabsorption rather than a specific lactose maldigestion is a significant problem in diarrheic calves. Diarrheic calves appear to digest and absorb lactose when fed in small amounts.",,"['Nappert, G', 'Hamilton, D', 'Petrie, L', 'Naylor, J M']",,,,
,PMC,In utero transmission of Mycoplasma pulmonis in experimentally infected Sprague-Dawley rats.,,PMC280949,,,"Genital mycoplasmosis is important as an animal model for the interaction between infectious agents and the host during pregnancy as well as in its own right as a confounding variable affecting research projects in which the rat is used as a model to study reproductive function and physiology. We report the in utero transmission of Mycoplasma pulmonis and the development of placentitis, amnionitis, and mild fetal bronchopneumonia in Sprague-Dawley rats. A minimum of 10 days prior to breeding, specific-pathogen-free female Sprague-Dawley rats were infected by intravaginal inoculation with 3 x 10(7) CFU of M. pulmonis X1048 or with an equal volume of sterile broth. Rats and fetuses were subjected to necropsy at days 11, 14, and 18 of gestation. M. pulmonis was able to invade the placenta, cross the placental barrier, and establish an amniotic fluid infection by gestational day 14. It was isolated from the oropharynx and lungs of fetuses at gestational day 18. The placenta was more frequently colonized than amniotic fluid, followed by the fetal oropharynx and lungs, supporting an ascending route of infection. Histopathological evidence also support an active infection, with lesions compatible with placentitis, amnionitis, and mild fetal bronchopneumonia. M. pulmonis can traverse the placenta, resulting in infection of the amniotic fluid and in utero transmission of the microorganism to the developing fetus.",,"['Steiner, D A', 'Uhl, E W', 'Brown, M B']",,,,
,PMC,NS3 is a serine protease required for processing of hepatitis C virus polyprotein.,,PMC237769,,,"Hepatitis C virus (HCV) possesses a positive-sense RNA genome which encodes a large polyprotein of 3,010 amino acids. Previous data and sequence analysis have indicated that this polyprotein is processed by cellular proteases and possibly by a virally encoded serine protease localized in the N-terminal domain of nonstructural protein NS3. To characterize the molecular aspects of HCV protein biogenesis and to clearly identify the protein products derived from the HCV genome, we have examined HCV polyprotein expression by using the vaccinia virus T7 transient expression system in transfected cells and by cell-free translation studies. HCV proteins were identified by immunoprecipitation with region-specific antisera. Here we show that the amino-terminal region of the HCV polyprotein is processed in vitro by cellular proteases releasing three structural proteins: p21 (core), gp37 (E1), and gp61 (E2). Processing of the nonstructural region of HCV was evident in transfected cells. Two proteins of 24 and 68 kDa were immunoprecipitated with anti-NS2 and NS3 antisera, respectively. Antiserum against NS4 recognized three proteins of 6, 26, and 31 kDa, while antisera specific for NS5 immunoprecipitated two polypeptides of 56 and 65 kDa, indicating that each of these two genes encodes at least two different proteins. When the NS3 protease domain was inactivated by replacing the proposed catalytic Ser-1165 with Ala, processing at several sites was abolished. When Ser-1164 was mutated to Ala, no effect on the processing was observed. Cleavage activities at three of the four sites affected by NS3 were shown to occur in trans, while processing at the carboxy terminus of NS3 could not be mediated in trans. These results provide a detailed description of the protein products obtained from the processing of the HCV polyprotein. Furthermore, the data obtained implicate NS3 as a serine protease and demonstrate that a catalytically active NS3 is necessary for cleavage of the nonstructural region of HCV.",,"['Tomei, L', 'Failla, C', 'Santolini, E', 'De Francesco, R', 'La Monica, N']",,,,
,PMC,Nonhomologous RNA recombination during negative-strand synthesis of flock house virus RNA.,,PMC237750,,,"During sequential replicative passages of viral RNA from the nodavirus flock house virus, spontaneous deletion of RNA sequences occurred frequently. Families of deleted RNA molecules were derived from both segments of the bipartite viral genome and found to contain single, double, or triple deletions. These deletions were attributed to template switching by the flock house virus RNA replicase, resulting in recombination between distant sequences and excision of the intervening nucleotides. From sequence analysis of the recombination junctions, we concluded that the process of template switching was influenced by both the primary sequence and the secondary structure of the RNA and that it occurred predominantly during synthesis of RNA negative strands.",,"['Li, Y', 'Ball, L A']",,,,
,PMC,Retention of a cis Golgi protein requires polar residues on one face of a predicted alpha-helix in the transmembrane domain.,,PMC300979,,,"The first membrane-spanning domain (m1) of the model cis Golgi protein M (formerly called E1) from the avian coronavirus infectious bronchitis virus is required for targeting to the Golgi complex. When inserted in place of the membrane-spanning domain of a plasma membrane protein (vesicular stomatitis virus G protein), the chimeric protein (""Gm1"") is retained in the Golgi complex of transfected cells. To determine the precise features of the m1 domain responsible for Golgi targeting, we produced single amino acid substitutions in m1 and analyzed their effects on localization of Gm1. Expression at the plasma membrane was used as the criterion for loss of Golgi retention. Rates of oligosaccharide processing were used as a measure of rate and efficiency of transport through the Golgi complex. We identified four uncharged polar residues that are critical for Golgi retention of Gm1 (Asn465, Thr469, Thr476, and Gln480). These residues line one face of a predicted alpha-helix. Interestingly, when the m1 domain of the homologous M protein from mouse hepatitis virus is inserted into the G protein reporter, the chimeric protein is not efficiently retained in the Golgi complex, but transported to the cell surface. Although it possesses three of the four residues we identified as important in the avian m1 sequence, other residues in the membrane-spanning domain from the mouse protein must prevent efficient recognition of the polar face within the lipid bilayer of the cis Golgi.",,"['Machamer, C E', 'Grim, M G', 'Esquela, A', 'Chung, S W', 'Rolls, M', 'Ryan, K', 'Swift, A M']",,,,
,PMC,"On the directional specificity of ribosome frameshifting at a ""hungry"" codon.",,PMC46742,,,"Limitation for aminoacyl-tRNA promotes ribosome frameshifting at certain sites. We have previously demonstrated ribosome frameshifting to the right (3') at an AAG site in one context, and to the left (5') at an AAG site in a different context. Here, we demonstrate that the ""rightwing"" context is largely specific for frameshifting to the right, and the ""leftwing"" context is largely specific for frameshifting to the left. Analysis of these context rules, and the conversion of a sequence that promotes leftward frameshifting to one that promotes rightward frameshifting, demonstrated here, permits us to define a minimal heptanucleotide sequence sufficient for shiftiness in each direction at an AAG codon whose lysyl-tRNA is in short supply.",,"['Lindsley, D', 'Gallant, J']",,,,
,PMC,Identification of B-cell epitopes on the S4 subunit of pertussis toxin.,,PMC280863,,,"The main purpose of the present study was to identify B-cell epitopes on the S4 subunit of pertussis toxin (PT) by the synthetic peptide approach. Two strategies were followed: (i) screening of two series of overlapping peptides (12- and 25-residue peptides) covering the entire S4 sequence by a panel of murine monoclonal anti-PT antibodies and various polyclonal anti-PT antisera in an enzyme-linked immunosorbent assay (ELISA), and (ii) analysis of the S4 amino acid sequence by a predictive algorithm followed by synthesis and immunization of mice with the predicted peptides coupled to diphtheria toxoid. The anti-peptide conjugate antisera were tested in an ELISA for cross-reactivity with native PT, B oligomer, and S4. Screening of the free peptides in an ELISA by the PT antisera indicated the presence of six B-cell epitope-containing domains covered by residues 18 to 32, 33 to 46, 39 to 52, 51 to 65, 71 to 84, and 91 to 106. None of the peptides, however, were recognized by the monoclonal anti-PT antibodies in an ELISA. Immunization with six computer-predicted peptides (B1 to B6) and three potential T-cell epitopes (T1 to T3) gave rise to very high antibody responses towards the homologous conjugates. With the exception of the anti-T1/diphtheria toxoid antisera, all anti-peptide conjugate antisera cross-reacted with PT in an ELISA at different levels. None of these anti-peptide conjugate antisera, however, showed any PT-neutralizing effect as measured by the Chinese hamster ovary cell assay and the leukocytosis-promoting activity test. The results of the present study suggest that discontinuous epitopes are predominant in the S4 subunit of native PT.",,"['Ibsen, P H', 'Holm, A', 'Petersen, J W', 'Olsen, C E', 'Heron, I']",,,,
,PMC,Sensitivity of NCI-H292 human lung mucoepidermoid cells for respiratory and other human viruses.,,PMC265568,,,"NCI-H292 mucoepidermoid carcinoma cells from human lungs were shown in an earlier report to be a fully adequate substitute for primary rhesus monkey kidney (MK) cells for the isolation and propagation of the human paramyxoviruses. Although sensitivity for ortho- and paramyxoviruses was the principal reason for using MK cells, the cells were also sensitive to many other viruses, which constituted another important value of MK cells. That MK cells supported the initial isolation and growth of so many respiratory viruses made it a mandatory cell type for any clinical laboratory. We therefore felt it was imperative to evaluate the virus spectrum of NCI-H292 cells, which are being used as a substitute for MK cells in many laboratories. In the present report, we show that NCI-H292 cells are sensitive for vaccinia virus, herpes simplex virus, adenoviruses, BK polyomavirus, reoviruses, measles virus, respiratory syncytial virus, some strains of influenza virus type A, most enteroviruses, and rhinoviruses, in addition to the parainfluenza and mumps viruses originally reported. Furthermore, these viruses replicate in NCI-H292 cells to the same virus and antigen titers and at the same speed of replication as they do in their usually preferred cells. The NCI-H292 cells are therefore an excellent substitute for MK cells in terms of laboratory safety, ease of availability, paramyxovirus isolation, and broad virus spectrum but cannot substitute for MK cells for the isolation of influenza viruses.",,"['Hierholzer, J C', 'Castells, E', 'Banks, G G', 'Bryan, J A', 'McEwen, C T']",,,,
,PMC,Cross-protection against lymphocytic choriomeningitis virus mediated by a CD4+ T-cell clone specific for an envelope glycoprotein epitope of Lassa virus.,,PMC237696,,,"Recombinant vaccinia virus expressing the Lassa virus (LV) envelope glycoprotein precursor, V-LSGPC, was used to study the basis of LV-induced cross-protective immunity against the closely related arenavirus lymphocytic choriomeningitis virus (LCMV). C3H/HeJ mice primed with V-LSGPC developed neither circulating antibodies nor CD8+ cytotoxic T cells specific for LCMV, yet they resisted a normally lethal LCMV challenge. Spleen cells from such mice gave a proliferative response to LCMV in vitro that was inhibitable by anti-CD4 antibody. Synthetic peptides corresponding to predicted T-cell sites common to the envelope glycoprotein precursor (GP-C) of LV and that of LCMV were used to map the specificity of the proliferative response to an epitope located between amino acids 403 and 417 of LV GP-C. Several CD4+ T-cell clones specific for the 403-417 peptide were isolated and found to produce gamma interferon in response to both the peptide and LCMV. One of these clones, C9, was selected for further study. C9 lysed I-AK-bearing target cells, and when adoptively transferred to C3H/HeJ mice, it was capable of mediating both a peptide-specific delayed hypersensitivity reaction and resistance to lethal LCMV challenge. These collective findings demonstrate, for the first time, that CD4+ T cells can play a major role in arenavirus-specific cross-protective immunity.",,"['La Posta, V J', 'Auperin, D D', 'Kamin-Lewis, R', 'Cole, G A']",,,,
,PMC,Effect of intergenic consensus sequence flanking sequences on coronavirus transcription.,,PMC237672,,,"Insertion of a region, including the 18-nucleotide-long intergenic sequence between genes 6 and 7 of mouse hepatitis virus (MHV) genomic RNA, into an MHV defective interfering (DI) RNA leads to transcription of subgenomic DI RNA in helper virus-infected cells (S. Makino, M. Joo, and J. K. Makino, J. Virol. 66:6031-6041, 1991). In this study, the subgenomic DI RNA system was used to determine how sequences flanking the intergenic region affect MHV RNA transcription and to identify the minimum intergenic sequence required for MHV transcription. DI cDNAs containing the intergenic region between genes 6 and 7, but with different lengths of upstream or downstream flanking sequences, were constructed. All DI cDNAs had an 18-nucleotide-long intergenic region that was identical to the 3' region of the genomic leader sequence, which contains two UCUAA repeat sequences. These constructs included 0 to 1,440 nucleotides of upstream flanking sequence and 0 to 1,671 nucleotides of downstream flanking sequence. An analysis of intracellular genomic DI RNA and subgenomic DI RNA species revealed that there were no significant differences in the ratios of subgenomic to genomic DI RNA for any of the DI RNA constructs. DI cDNAs which lacked the intergenic region flanking sequences and contained a series of deletions within the 18-nucleotide-long intergenic sequence were constructed to determine the minimum sequence necessary for subgenomic DI RNA transcription. Small amounts of subgenomic DI RNA were synthesized from genomic DI RNAs with the intergenic consensus sequences UCUAAAC and GCUAAAC, whereas no subgenomic DI RNA transcription was observed from DI RNAs containing UCUAAAG and GCTAAAG sequences. These analyses demonstrated that the sequences flanking the intergenic sequence between genes 6 and 7 did not play a role in subgenomic DI RNA transcription regulation and that the UCUAAAC consensus sequence was sufficient for subgenomic DI RNA transcription.",,"['Makino, S', 'Joo, M']",,,,
,PMC,Definition of a subset of human peripheral blood mononuclear cells that are permissive to human cytomegalovirus infection.,,PMC237655,,,"The identity of cells responsible for transmission of human cytomegalovirus (HCMV) in blood products or bone marrow transplants is unknown. We have tested the capacity of HCMV to in vitro infect human peripheral blood mononuclear cells (PBMC) from healthy donors and found that certain PBMC are permissive to HCMV infection. In vitro-infected viable cells were double stained for surface expression of different HMCV proteins and for cell-type-specific antigens to allow the identification of sensitive cells. All analysis were performed on viable cells, using HCMV-specific monoclonal antibodies and automated flow cytofluorimetry. PBMC were infected either with the laboratory-adapted HCMV strain AD169 or with a virus isolate obtained from a viremic patient. Up to 25% of all PBMC could express the major immediate-early antigen as well as the pp65 antigen, known at the lower matrix protein. Infected cells were mainly CD14+ monocytes, but also a small population of large CD8+ cells were susceptible to HCMV infection. CD19+ B lymphocytes were resistant to HCMV infection. Different populations of infected cells were enriched by using Dynabeads coated with cell-type-specific antibodies, and the presence of infectious virus was demonstrated by incubating the selected and sonicated cell material on human fibroblasts. Only material from infected monocytes and from CD3+ CD8+ cells gave rise to HCMV-specific plaques. The presence of HCMV mRNA as a sign of active viral transcription of the major immediate-early and late pp150 genes in infected cells was demonstrated by using nested reversed polymerase chain reaction. A common denominator was found for all cells that could be infected with HCMV. The CD13 antigen, a 130- to 150-kDa integral membrane protein identical to the enzyme aminopeptidase N, was expressed on all HCMV-permissive cells.",,"['Söderberg, C', 'Larsson, S', 'Bergstedt-Lindqvist, S', 'Möller, E']",,,,
,PMC,Biochemical and genetic evidence for a pseudoknot structure at the 3' terminus of the poliovirus RNA genome and its role in viral RNA amplification.,,PMC237632,,,"The sequences in the plus-stranded poliovirus RNA genome that dictate the specific amplification of viral RNA in infected cells remain unknown. We have analyzed the structure of the 3' noncoding region of the viral genome by thermodynamic-based structure calculation and by chemical and enzymatic probing of in vitro-synthesized RNAs and provide evidence for the existence of an RNA pseudoknot structure in this region. To explore the functional significance of this structure, revertants of a mutant bearing a lesion in the proposed pseudoknot and exhibiting a temperature-sensitive defect in viral RNA synthesis were isolated and mapped. The results of this genetic analysis established a correlation between the structure of the 3' terminus of the viral RNA and its function in vivo in RNA amplification. Furthermore, phylogenetic analysis indicated that a similar structure could be formed in coxsackievirus B1, a related enterovirus, which further supports a role for the pseudoknot structure in viral RNA amplification in infected cells.",,"['Jacobson, S J', 'Konings, D A', 'Sarnow, P']",,,,
,PMC,Schizosaccharomyces pombe ypt5: a homologue of the rab5 endosome fusion regulator.,,PMC300965,,,"The ypt/rab proteins are a family of small GTP-binding proteins thought to be required for different stages of membrane traffic. From the fission yeast Schizosaccharomyces pombe we have isolated and characterized ypt5, a gene encoding a homologue of rab5, a mammalian protein apparently involved in regulating fusion of early endosomes. Recombinant ypt5 protein bound GTP. The ypt5 gene was found to be essential for viability on minimal media, but ypt5-disrupted cells grew slowly on some rich media and accumulated a population of small vesicles not observed in wild-type cells. Canine rab5 cDNA could replace the ypt5 gene in S. pombe and restore normal growth and viability. Ypt5 protein expressed in mammalian cells colocalized with the transferrin receptor to early endosomes. Thus, molecular aspects of the early endocytic pathway may be conserved between mammalian cells and S. pombe and hence may be amenable to genetic analysis.",,"['Armstrong, J', 'Craighead, M W', 'Watson, R', 'Ponnambalam, S', 'Bowden, S']",,,,
,PMC,Structural requirements for efficient translational frameshifting in the synthesis of the putative viral RNA-dependent RNA polymerase of potato leafroll virus.,,PMC309480,,,"The putative RNA-dependent RNA polymerase of potato leafroll luteovirus (PLRV) is expressed by -1 ribosomal frameshifting in the region where the open reading frames (ORF) of proteins 2a and 2b overlap. The signal responsible for efficient frameshift is composed of the slippery site UUUAAAU followed by a sequence that has the potential to adopt two alternative folding patterns, either a structure involving a pseudoknot, or a simple stem-loop structure. To investigate the structure requirements for efficient frameshifting, mutants in the stem-loop or in the potential pseudoknot regions of a Polish isolate of PLRV (PLRV-P) have been analyzed. Mutations that are located in the second stem (S2) of the potential pseudoknot structure, but are located in unpaired regions of the alternative stem-loop structure, reduce frameshift efficiency. Deletion of the 3' end sequence of the alternative stem-loop structure does not reduce frameshift efficiency. Our results confirm that -1 frameshift in the overlap region depends on the slippery site and on the downstream positioned sequence, and propose that in PLRV-P a pseudoknot is required for efficient frameshifting. These results are in agreement with those recently published for the closely related beet western yellows luteovirus (BWYV).",,"['Kujawa, A B', 'Drugeon, G', 'Hulanicka, D', 'Haenni, A L']",,,,
,PMC,Flock house virus: down-regulation of subgenomic RNA3 synthesis does not involve coat protein and is targeted to synthesis of its positive strand.,,PMC237594,,,"Flock house virus is a small insect virus with a bipartite RNA genome consisting of RNA1 and RNA2. RNA3 is a subgenomic element encoded by RNA1, the genomic segment required for viral RNA synthesis (T. M. Gallagher, P. D. Friesen, and R. R. Rueckert, J. Virol. 46:481-489, 1983). Synthesis of RNA3 is strongly inhibited by RNA2, the gene for viral coat protein. Evidence that coat protein is not the regulatory element was obtained by using a defective interfering RNA2 which was messenger inactive. It was also found that RNA2 selectively down-regulated synthesis of positive-strand RNA3 but not of its complementary negative strand. cDNA-generated RNA2 transcripts, carrying four extra nonviral bases at the 3' end, failed to repress synthesis of RNA3 but recovered this activity after a single passage in Drosophila cells in the presence of RNA1, suggesting that down-regulation of RNA3 synthesis is controlled by competition with RNA2 for viral replicase.",,"['Zhong, W', 'Rueckert, R R']",,,,
,PMC,Analysis of effects of tRNA:message stability on frameshift frequency at the Escherichia coli RF2 programmed frameshift site.,,PMC309422,,,"The codon that is in-frame prior to +1 frameshifting at the E.coli prfB (RF2 gene) frameshift site is randomized to create thirty-two variants. These alleles vary 1000-fold in frameshift-dependent expression in fusions to lacZ. Frameshifting is more frequent at sites where the in-frame codon ends in uridine, as if third position wobble pairs to message uridine facilitate slippage into the +1 frame. Consistent with other studies of programmed frameshift sites, efficient frameshifting depends on stable message:tRNA base pairs after rephasing. For complexes with mispairs, frameshift frequency depends on the nature, number, and position of mispairs. Central purine:purine mispairs are especially inhibitory. Relative stabilities of +1 rephased complexes are estimated from published data on the stabilities of tRNA:tRNA complexes. Stability correlates with frameshifting over its entire range, which suggests that stability is an important determinant of the probability of translation of the rephased complex.",,"Curran, J F",,,,
,PMC,Nasal IgA response in wheezy infants.,,PMC1029267,,,"It is unknown why some infants wheeze during upper respiratory tract infections. One possibility is that secretory IgA, which has a major role in mucosal defence against viral infection, might be deficient in wheezy infants. The nasal IgA response to upper respiratory tract infection in 32 wheezy infants (median age 5.8 months) was compared with nine siblings (median age 2.6 years) who had nasal symptoms only. Nasal lavage was performed during infections and on follow up when free from symptoms, using inulin as a marker of dilution to determine absolute concentrations of IgA in the nasal secretions. The two groups showed a similar increase in total IgA and total protein levels during infection, but secretory IgA concentrations were unchanged. This study shows that wheezy infants have a normal nasal IgA response to infection and that the increase in total IgA during early infection is due to plasma exudation rather than increased production of secretory IgA.",,"['Balfour-Lynn, I M', 'Valman, B', 'Silverman, M', 'Webster, A D']",,,,
,PMC,Physical and chemical methods for enhancing rapid detection of viruses and other agents.,,PMC358275,,,"Viral replication events can be enhanced by physical, chemical, or heat treatment of cells. The centrifugation of cells can stimulate them to proliferate, reduce their generation times, and activate gene expression. Human endothelial cells can be activated to release cyclo-oxygenase metabolites after rocking for 5 min, and mechanical stress can stimulate endothelial cells to proliferate. Centrifugation of virus-infected cultures can increase cytopathic effects (CPE), enhance the number of infected cells, increase viral yields, and reduce viral detection times and may increase viral isolation rates. The rolling of virus-infected cells also has an effect similar to that of centrifugation. The continuous rolling of virus-infected cultures at < or = 2.0 rpm can enhance enterovirus, rhinovirus, reovirus, rotavirus, paramyxovirus, herpesvirus, and vaccinia virus CPE or yields or both. For some viruses, the continuous rolling of infected cell cultures at 96 rpm (1.9 x g) is superior to rolling at 2.0 rpm for viral replication or CPE production. In addition to centrifugation and rolling, the treatment of cells with chemicals or heat can also enhance viral yields or CPE. For example, the treatment of virus-infected cells with dimethyl sulfoxide can enhance viral transformation, increase plaque numbers and plaque size, increase the number of cells producing antigens, and increase viral yields. The infectivity of fowl plague virus is increased by 80-fold when 4% dimethyl sulfoxide is added to culture medium immediately after infection. The heat shocking of virus-infected cells also has been shown to have a stimulatory effect on the replication events of cytomegalovirus, Epstein-Barr virus, and human immunodeficiency virus. The effects of motion, chemicals, or heat treatments on viral replication are not well understood. These treatments apparently activate cells to make them more permissive to viral infection and viral replication. Perhaps heat shock proteins or stress proteins are a common factor for this enhancement phenomenon. The utility of these treatments alone or in combination with other methods for enhancing viral isolation and replication in a diagnostic setting needs further investigation.",,"Hughes, J H",,,,
,PMC,Prevalence of viral antibodies and helminths in field populations of house mice (Mus domesticus) in southeastern Australia.,,PMC2272274,,,"A 13-month study of wild mice (Mus domesticus) in wheatlands in southeastern Australia contrasted changes in the seroprevalence of antibody to 13 viruses and the occurrence of helminths with changes in their population dynamics. Mice were seropositive for mouse hepatitis virus (MHV), rotavirus, minute virus of mice (MVM), mouse adenovirus (MAdV), reovirus (reo 3), and murine cytomegalovirus (MCMV). The seroprevalences of all but rotavirus varied significantly with time and increased with host density. Near the end of the study, host density declined rapidly and the seroprevalence of MVM and reo 3 increased significantly. These two viruses had low seroprevalence when host survival was high and high seroprevalence when host survival was low, indicating they may play a role in regulating mouse populations. In the case of MVM, there was evidence of a viral epizootic during the decline in mouse abundance. The prevalence of four helminths (Taenia taeniaeformis, Syphacia obvelata, and Vampirolepis spp.) differed significantly with time but showed no apparent association with host density. These findings highlight the need for further study on the effect of viruses on the population dynamics of mice.",,"['Singleton, G. R.', 'Smith, A. L.', 'Shellam, G. R.', 'Fitzgerald, N.', 'Müller, W. J.']",,,,
,PMC,"Pathological and immunological effects of ingesting L-tryptophan and 1,1'-ethylidenebis (L-tryptophan) in Lewis rats.",,PMC288031,,,"The eosinophilia-myalgia syndrome (EMS) has been associated with ingestion of L-tryptophan (L-TRP) produced by a single manufacturer. Epidemiological data implicated 1,1'-ethylidenebis (L-tryptophan) (EBT) (peak 97 or peak E) as a possible etiologic agent. We showed previously that Lewis rats treated with the L-TRP implicated in EMS develop fasciitis and perimyositis similar to those seen in human EMS. We now report the pathology associated with the treatment of Lewis rats with synthetic EBT and/or L-TRP. All animals treated for 6 wk with case-associated L-TRP or EBT developed significant myofascial thickening, compared with animals in the vehicle control and control L-TRP groups. However, even those animals receiving the control L-TRP showed a mild but significant increase in the thickness of the myofascia, compared with vehicle-treated control animals. All animals except vehicle controls also exhibited significant pancreatic pathology, including fibrosis and acinar changes. Only animals treated with case-associated L-TRP for 6 wk showed evidence of immune activation with increased frequency of CD8, Ia, and IL-2 receptor-positive cells in the peripheral blood. Animals receiving L-TRP or EBT for < 6 wk did not show significant differences in myofascial thickness, although these animals did show pancreatic acinar changes. Although these results demonstrate for the first time the pathological effects of EBT, they do not rule out the possibility that other impurities in the EMS-case-associated L-TRP may also contribute to some of the features of EMS.",,"['Love, L A', 'Rader, J I', 'Crofford, L J', 'Raybourne, R B', 'Principato, M A', 'Page, S W', 'Trucksess, M W', 'Smith, M J', 'Dugan, E M', 'Turner, M L']",,,,
,PMC,A monoclonal antibody which blocks infection with feline immunodeficiency virus identifies a possible non-CD4 receptor.,,PMC237540,,,"Monoclonal antibody vpg15 detects a 24-kDa cell surface protein on feline cells permissive for infection with feline immunodeficiency virus (FIV). The antibody blocks infection of FIV-susceptible cells, and expression of the vpg15 marker is decreased in FIV-infected cells in vitro. These results suggest that the antibody may recognize an FIV receptor distinct from CD4.",,"['Hosie, M J', 'Willett, B J', 'Dunsford, T H', 'Jarrett, O', 'Neil, J C']",,,,
,PMC,Characterization of a glial cell line persistently infected with borna disease virus (BDV): influence of neurotrophic factors on BDV protein and RNA expression.,,PMC237515,,,"Borna disease virus (BDV) infects cells of the nervous system in a wide range of species. Previous work suggests that there are differences in BDV replication in neuronal cells and glial cells. Many neurons are lysed by the immunopathologic response to BDV; lysis of dentate gyrus neurons in the absence of encephalitis is seen in rats inoculated with BDV as neonates. In contrast, persistently BDV-infected astrocytes increase over the course of BDV infection. Therefore, we compared BDV replication in neuronal (SK-N-SH and SK-N-SHEP) and astrocytic (C6) cell lines. While SK-N-SH cells produced more infectious virions per cell, the C6 cells contained more BDV proteins and RNA. BDV sequences in the supernatants of both cell types were identified, despite low titers of infectious virus, suggesting the release of incomplete virions into the medium. C6 cells secreted a factor or factors into the medium that enhanced the production of BDV proteins and RNA in other cell lines. In addition, nerve growth factor treatment produced the same enhancement. Thus, BDV replication in certain neural cells in vitro may be linked to the production of cell-specific factors which affect viral replication.",,"['Carbone, K M', 'Rubin, S A', 'Sierra-Honigmann, A M', 'Lederman, H M']",,,,
,PMC,Fusion formation by the uncleaved spike protein of murine coronavirus JHMV variant cl-2.,,PMC237484,,,"The fusogenic properties of the uncleaved spike (S) protein of murine coronavirus JHMV variant cl-2 were studied by expressing the S protein with a deleted putative cleavage site. The amino acid sequence of the putative cleavage site, Arg-Arg-Ala-Arg-Arg, was replaced by Arg-Thr-Ala-Leu-Glu by in vitro mutagenesis of the cl-2 S protein cDNA. Recombinant vaccinia viruses containing the cl-2 S cDNA [RVV t(+)] or the mutated cDNA [RVV t(-)] were constructed and monitored for fusion formation and cleavage of the expressed S proteins. When cultured DBT cells were infected with RVV t(+) at a multiplicity of infection of 0.5, fusion formation was first observed at 10 to 12 h postinoculation and spread throughout the whole culture by 20 to 24 h postinoculation. In cells infected with RVV t(-) under the same conditions, fusion formation appeared by 12 to 14 h. This result represented a 2- to 4-h delay in the onset of fusion, compared with its appearance in cells expressing the wild-type S protein. By 25 to 30 h, most of the cells infected by RVV t(-) had fused. By immunoprecipitation and Western blotting (immunoblotting), the 170-kDa S protein was detected in DBT cells expressing the wild-type S protein and the mutated S protein. However, interestingly, the cleavage products of the S protein, S1 and S2, were not detected in RVV t(-)-infected cells, producing the mutated S protein, even though fusion was clearly visible. Both products were, of course, detected in RVV t(+)-infected DBT cells, producing the wild-type S protein. The same results concerning the fusion formation and cleavage properties of the S proteins were reproduced by the transiently expressed S proteins. These results suggest that the cleavage event in the S protein of murine coronavirus JHMV is not a prerequisite for fusion formation but that it does facilitate fusion formation.",,"Taguchi, F",,,,
,PMC,Identification of an immunodominant linear neutralization domain on the S2 portion of the murine coronavirus spike glycoprotein and evidence that it forms part of complex tridimensional structure.,,PMC237483,,,"Numerous studies have demonstrated that the spike glycoprotein of coronaviruses bears major determinants of pathogenesis. To elucidate the antigenic structure of the protein, a panel of monoclonal antibodies was studied by competitive ELISA, and their reactivities were assayed against fragments of the murine coronavirus murine hepatitis virus strain A59 S gene expressed in prokaryotic vectors. An immunodominant linear domain was localized within the predicted stalk, S2, of the peplomer. It is recognized by several neutralizing antibodies. Other domains were also identified near the proteolytic cleavage site, in the predicted globular head, S1, and in another part of the stalk. Furthermore, competition results suggest that the immunodominant functional domain forms part of a complex three-dimensional structure. Surprisingly, some antibodies which have no antiviral biological activities were shown to bind the immunodominant neutralization domain.",,"['Daniel, C', 'Anderson, R', 'Buchmeier, M J', 'Fleming, J O', 'Spaan, W J', 'Wege, H', 'Talbot, P J']",,,,
,PMC,Mouse hepatitis virus strain A59 and blocking antireceptor monoclonal antibody bind to the N-terminal domain of cellular receptor.,,PMC45950,,,"Mouse hepatitis virus (MHV) strain A59 uses as cellular receptors members of the carcinoembryonic antigen family in the immunoglobulin superfamily. Recombinant receptor proteins with deletions of whole or partial immunoglobulin domains were used to identify the regions of receptor glycoprotein recognized by virus and by antireceptor monoclonal antibody CC1, which blocks infection of murine cells. Monoclonal antibody CC1 and MHV-A59 virions bound only to recombinant proteins containing the entire first domain of MHV receptor. To determine which of the proteins could serve as functional virus receptors, receptor-negative hamster cells were transfected with recombinant deletion clones and then challenged with MHV-A59 virions. Receptor activity required the entire N-terminal domain with either the second or the fourth domain and the transmembrane and cytoplasmic domains. Recombinant proteins lacking the first domain or its C-terminal portion did not serve as viral receptors. Thus, like other virus receptors in the immunoglobulin superfamily, including CD4, poliovirus receptor, and intercellular adhesion molecule 1, the N-terminal domain of MHV receptor is recognized by the virus and the blocking monoclonal antibody.",,"['Dveksler, G S', 'Pensiero, M N', 'Dieffenbach, C W', 'Cardellichio, C B', 'Basile, A A', 'Elia, P E', 'Holmes, K V']",,,,
,PMC,A role for aminopeptidase N in Na(+)-dependent amino acid transport in bovine renal brush-border membranes.,,PMC1132382,,,"A monoclonal antibody FD19 which removes reconstitutable Na(+)-dependent amino acid transport activity from solubilized bovine renal brush-border membrane vesicles was found to react specifically with the enzyme aminopeptidase N. Cleavage of aminopeptidase N from the membranes with papain inhibited Na(+)-dependent amino acid transport activity without affecting that of alpha-methyl D-glucoside. Removal of aminopeptidase substantially increased the Km values for the Na(+)-dependent transport of alanine, glutamine, leucine and phenylalanine without affecting the Vmax. Both Na(+)-dependent amino acid transport and aminopeptidase activity in intact vesicles were competitively inhibited by amino acids with very similar specificity. These results suggest that the amino acid-binding sites of aminopeptidase N and the transporter interact in some way to increase the Km of the transport process for its substrates. However, independent direct inactivation of the transport system by papain cannot be ruled out.",,"['Plakidou-Dymock, S', 'Tanner, M J', 'McGivan, J D']",,,,
,PMC,Contamination of DNA database sequence entries with Escherichia coli insertion sequences.,,PMC309200,,,,,"Binns, M",,,,
,PMC,Differential response to frameshift signals in eukaryotic and prokaryotic translational systems.,,PMC309131,,,"The genomic RNA of beet western yellows virus (BWYV) contains a potential translational frameshift signal in the overlap region of open reading frames ORF2 and ORF3. The signal, composed of a heptanucleotide slippery sequence and a downstream pseudoknot, is similar in appearance to those identified in retroviral RNAs. We have examined whether the proposed BWYV signal functions in frameshifting in three translational systems, i.c. in vitro in a reticulocyte lysate or a wheat germ extract and in vivo in E. coli. The efficiency of the signal in the eukaryotic system is low but significant, as it responds strongly to changes in either the slip sequence or the pseudoknot. In contrast, in E. coli there is hardly any response to the same changes. Replacing the slip sequence to the typical prokaryotic signal AAAAAAG yields more than 5% frameshift in E. coli. In this organism the frameshifting is highly sensitive to changes in the slip sequence but only slightly to disruption of the pseudoknot. The eukaryotic assay systems are barely sensitive to changes in either AAAAAAG or in the pseudoknot structure in this construct. We conclude that eukaryotic frameshift signals are not recognized by prokaryotes. On the other hand the typical prokaryotic slip sequence AAAAAAG does not lead to significant frameshifting in the eukaryote. In contrast to recent reports on the closely related potato leafroll virus (PLRV) we show that the frameshifting in BWYV is pseudoknot-dependent.",,"['Garcia, A', 'van Duin, J', 'Pleij, C W']",,,,
,PMC,The enteritis complex in domestic rabbits: A field study,,PMC1686380,,,"A study of the causative agents of enteritis in domestic rabbits from 44 different accessions is described. In descending order of frequency, the organisms most commonly demonstrated were intestinal and hepatic coccidia (Eimeria species), Escherichia coli, Clostridium spp., Salmonella, Bacillus piliformis, and rotavirus. The species of Eimeria identified included those moderately pathogenic and coccidia of low pathogenicity. Using seven antisera against known enterpathogenic strains of E. coli, only one strain, O15, was identified in three cases. Clostridium perfringens or C. spiroforme was demonstrated in the intestinal contents in 11 cases, and lesions compatible with clostridial enteropathy were identified on gross and histopathology. In a serological survey, over 50% of 200 fryer rabbits submitted to Ontario abattoirs and of animals from commercial rabbitries had detectable antibody to rotavirus, indicating the widespread distribution of rotaviral infections in this species. In the cases of enteritis studied, two or more potentially pathogenic organisms were frequently identified, emphasizing that several different organisms may be acting in concert to produce clinical disease.",,"['Percy, Dean H.', 'Muckle, C. Anne', 'Hampson, Robert J.', 'Brash, Marina L.']",,,,
,PMC,Acute respiratory illness in the community. Frequency of illness and the agents involved.,,PMC2271959,,,"Investigations of respiratory illnesses and infections in Tecumseh, Michigan, USA, were carried out in two phases, together covering 11 years. During the second phase, there were 5363 person-years of observation. Respiratory illness rates in both males and females peaked in the 1-2 year age group and fell thereafter. Adult females had more frequent illnesses than adult males; illnesses were less common in working women than in women not working outside the home. Isolation of viruses fell with increasing age; rhinoviruses were the most common isolate. Influenza infection rates, determined serologically, suggested relative sparing of young children from infection with type A (H1N1) and type B. Infection rates were highest in adult age groups for type A (H3N2). The isolation and serological infection rates were used to estimate the extent to which laboratory procedures underestimated the proportion of respiratory illnesses caused by each infectious agent; data from other studies were also used in this estimation. Severity of respiratory illnesses was assessed by the proportion of such illnesses that resulted in consultation of a physician. Rhinoviruses produced the greatest number of consultations. Overall, physician consultations were associated with 25.4% of respiratory illnesses.",,"['Monto, A. S.', 'Sullivan, K. M.']",,,,
,PMC,Impact of experimental genital mycoplasmosis on pregnancy outcome in Sprague-Dawley rats.,,PMC302774,,,"Specific-pathogen-free (SPF) female Sprague-Dawley rats were infected by intravaginal inoculation with 3 x 10(7) CFU of Mycoplasma pulmonis X1048 in 0.1 ml of Frey's broth or with an equal volume of sterile Frey's broth. A minimum of 10 days postinfection, rats were bred to noninfected males. Rats were necropsied at days 11, 14, and 18 of gestation and within 24 h of parturition. Throughout pregnancy, at least 50% of rats remained infected in the lower genital tract. At parturition, the major site of colonization was the respiratory tract (P = 0.02). M. pulmonis was not isolated from any site of any control rat. Pregnancy outcome was adversely affected by infection with M. pulmonis. Infected rats had significantly smaller litter sizes at day 18 of gestation (P < or = 0.01) and at term (P < or = 0.004). No statistically significant differences among the gestational stages in infected rats were noted for litter size. Total litter weight is a reflection of individual pup weight and of the number of pups born. Therefore, it was obvious that infected rats would have a significantly lower (P < or = 0.008) total litter weight than noninfected controls. However, when individual pup weights were considered, infected pups (n = 49) also had significantly lower (P < or = 0.0001) birth weights than did noninfected controls (n = 68). The incidence of an adverse pregnancy outcome at term (stillbirths, macerated fetuses, or resorptions) was higher (P < or = 0.01) in infected rats than in noninfected control rats. No stillborn pups or macerated fetuses were observed in any control term rats (n = 5). All control rats had live-born pups. Three infected rats had no live-born offspring. Resorptions were more common in infected rats than in control rats (P < or = 0.01). The mean number of resorptions per rat was greater in rats which went to term than in rats necropsied during gestation, indicating that the severity of disease was progressive. The rat is frequently the laboratory animal of choice for a wide variety of reproductive studies, and the experimental parameters that are most often measured (litter size, pup weight, and neonatal survival) were all adversely affected by genital mycoplasmosis. Genital mycoplasmosis is important as an animal model for the interaction of infectious agents and the host during pregnancy as well as in its own right as a confounding variable affecting research projects which use the rat as a model to study reproductive function and physiology.",,"['Steiner, D A', 'Brown, M B']",,,,
,PMC,Structure of a human rhinovirus complexed with its receptor molecule.,,PMC45692,,,"Cryoelectron microscopy has been used to determine the structure of a virus when complexed with its glycoprotein cellular receptor. Human rhinovirus 16 complexed with the two amino-terminal, immunoglobulin-like domains of the intercellular adhesion molecule 1 shows that the intercellular adhesion molecule 1 binds into the 12-A deep ""canyon"" on the viral surface. This result confirms the prediction that the viral-receptor attachment site lies in a cavity inaccessible to the host's antibodies. The atomic structures of human rhinovirus 14 and CD4, homologous to human rhinovirus 16 and intercellular adhesion molecule 1, showed excellent correspondence with observed density, thus establishing the virus-receptor interactions.",,"['Olson, N H', 'Kolatkar, P R', 'Oliveira, M A', 'Cheng, R H', 'Greve, J M', 'McClelland, A', 'Baker, T S', 'Rossmann, M G']",,,,
,PMC,A comparative evaluation of two sensitive serum neutralization tests for bovine herpesvirus-1 antibodies.,,PMC1263591,,,"Two sensitive serum neutralization (SN) tests for the detection of antibodies to bovine herpesvirus-1 (BHV-1) in bovine sera were evaluated. Both SN tests used a 24 h incubation of test sera with 100 CCID50 of BHV-1 before the addition of susceptible cells. The tests differed in the presence (C test) or absence (D test) of complement and were compared with a standard 1 h incubation SN test and the enzyme-linked immunosorbent assay (ELISA). Although the mean titer of the C test was twofold higher than the mean titer of the D test for 310 sera, the number of samples which were negative was not significantly different between tests. For 100 sera from herds with known reactors, which were negative in a 1 h incubation SN test, 32% tested positive in the C and D tests. Other investigations, including Western immunoblotting and radioimmune precipitation, suggest that the 24 h incubation tests produce some false positive results. In contrast, the 1 h incubation SN test and, to a much lesser extent, the ELISA appear to produce some false negative results. The C test was more sensitive than the D test for detecting an early immune response after experimental infection.",,"['Deregt, D', 'Cho, H J', 'Kozub, G C']",,,,
,PMC,Characterization of ribosomal frameshifting for expression of pol gene products of human T-cell leukemia virus type I.,,PMC237352,,,"For study of the pol gene expression of human T-cell leukemia virus type I (HTLV-I), RNA was transcribed in vitro from proviral DNA and translated in rabbit reticulocyte lysates. This cell-free translation resulted in two major translation products representing the Gag and Gag-Pro polyproteins. By contrast, the Gag-Pro-Pol polyprotein could be readily observed only when translation was performed with mutant mRNA in which the protease (pro) reading frame was aligned to gag to eliminate the frameshifting event in the gag-pro overlap. The results indicated that two independent ribosomal frameshifting events are required for expression of the HTLV-I pol gene product. Studies with mutant DNAs facilitated the characterization of the primary structure of the HTLV-I mRNA responsible for the ribosomal frameshift in the pro-pol overlap and demonstrated that the frameshift occurs at the signal sequence UUUAAAC. Direct amino acid sequencing of the transframe protein localized the site of the frameshift to the asparagine codon AAC.",,"['Nam, S H', 'Copeland, T D', 'Hatanaka, M', 'Oroszlan, S']",,,,
,PMC,Several members of the mouse carcinoembryonic antigen-related glycoprotein family are functional receptors for the coronavirus mouse hepatitis virus-A59.,,PMC237331,,,"Mouse hepatitis virus-A59 (MHV-A59), a murine coronavirus, can utilize as a cellular receptor MHVR, a murine glycoprotein in the biliary glycoprotein (BGP) subfamily of the carcinoembryonic antigen (CEA) family in the immunoglobulin superfamily (G.S. Dveksler, M. N. Pensiero, C. B. Cardellichio, R. K. Williams, G.-S. Jiang, K. V. Holmes, and C. W. Dieffenbach, J. Virol. 65:6881-6891, 1991). Several different BGP isoforms are expressed in tissues of different mouse strains, and we have explored which of these glycoproteins can serve as functional receptors for MHV-A59. cDNA cloning, RNA-mediated polymerase chain reaction analysis, and Western immunoblotting with a monoclonal antibody, CC1, specific for the N-terminal domain of MHVR showed that the inbred mouse strains BALB/c, C3H, and C57BL/6 expressed transcripts and proteins of the MHVR isoform and/or its splice variants but not the mmCGM2 isoform. In contrast, adult SJL/J mice, which are resistant to infection with MHV-A59, express transcripts and proteins only of the mmCGM2-related isoforms, not MHVR. These data are compatible with the hypothesis that the MHVR and mmCGM2 glycoproteins may be encoded by different alleles of the same gene. We studied binding of anti-MHVR antibodies or MHV-A59 virions to proteins encoded by transcripts of MHVR and mmCGM2 and two splice variants of MHVR, one containing two immunoglobulin-like domains [MHVR(2d)] and the other with four domains as in MHVR but with a longer cytoplasmic domain [MHVR(4d)L]. We found that the three isoforms tested could serve as functional receptors for MHV-A59, although only isoforms that include the N-terminal domain of MHVR were recognized by monoclonal antibody CC1 in immunoblots or by MHV-A59 virions in virus overlay protein blot assays. Thus, in addition to MHVR, both the two-domain isoforms, mmCGM2 and MHVR(2d), and the MHVR(4d)L isoform served as functional virus receptors for MHV-A59. This is the first report of multiple related glycoprotein isoforms that can serve as functional receptors for a single enveloped virus.",,"['Dveksler, G S', 'Dieffenbach, C W', 'Cardellichio, C B', 'McCuaig, K', 'Pensiero, M N', 'Jiang, G S', 'Beauchemin, N', 'Holmes, K V']",,,,
,PMC,New nucleotide sequence data on the EMBL File Server.,,PMC334548,,,,,,,,,
,PMC,Swine reproductive and respiratory syndrome in Québec: Isolation of an enveloped virus serologically-related to Lelystad virus,,PMC1481389,,,"Sera were collected from convalescent sows and sick piglets from six pig farms in southern Quebec that have experienced outbreaks of the so-called porcine reproductive and respiratory syndrome. By indirect immunoperoxidase, a few of these sera (4 of 14) (28.6%) were found to be positive for antibody to the Lelystad virus, whereas by indirect immunofluorescence 30 of 36 (83.3%) were positive for antibody to the antigenically-related American isolate ATCC-VR2332. Pregnant sows inoculated intranasally with filtered homogenates prepared from the lungs of necropsied piglets obtained from a seropositive farm developed fever, inappetence, and reproductive failure characterized by stillbirths and various stages of mummification. Lesions of interstitial pneumonia were induced in experimentally-infected specific pathogen-free piglets. A virus, having morphological and biological characteristics of viruses assigned to the family Togaviridae, was isolated from lung tissues of experimentally-infected animals; it could only be propagated in primary cultures of porcine alveolar macrophages. Identification of the virus was confirmed by indirect immunofluorescence using a monoclonal antibody directed against the nucleocapsid protein of the ATCC-VR2332 isolate and porcine sera that were found positive for antibody to both the Lelystad and ATCC-VR2332 isolates.",,"['Dea, Serge', 'Bilodeau, Robert', 'Athanassious, Raffat', 'Sauvageau, René', 'Martineau, Guy Pierre']",,,,
,PMC,Bovine coronavirus infection in Ontario 1990-1991,,PMC1481375,,,,,"['Carman, P. Suzanne', 'Hazlett, Murray J.']",,,,
,PMC,Liposome-mediated transfection of intact viral particles reveals that plasma membrane penetration determines permissivity of tissue culture cells to rotavirus.,,PMC443384,,,"Rotaviruses are an important cause of gastroenteritis in human infants. In vivo, rotavirus displays striking cell tropism with viral replication generally restricted to the villus tip enterocytes of the small intestine. We studied a panel of cell lines that vary significantly in their permissivity to rotavirus infection. L cells and HEp2 cells were relatively resistant to rotavirus infection compared with permissive Ma104 cells and HT29 cells. RNA transcription among the cell lines was proportional to antigen synthesis making a translational or posttranslational block an unlikely source of observed differences in susceptibility. All of the cell lines bound and internalized radiolabeled virus equally well, as measured by escape from surface protease treatment. Analysis of the escape of cell bound virus from neutralizing monoclonal antibody revealed that rotavirus did not immediately enter an eclipse phase in nonpermissive cells, but was internalized in an infectious form for several hours, possibly sequestered within endocytic vacuoles. L cells and HEp2 cells were as permissive as Ma104 and HT29 cells when rotavirus infection was mediated by transfection of single- or double-shelled rotavirus particles with cationic liposomes (Lipofectin). Rotavirus cell tropism in tissue culture cells is determined by the ability of infecting virions to traverse the plasma membrane of the cells into the cytoplasmic compartment.",,"['Bass, D M', 'Baylor, M R', 'Chen, C', 'Mackow, E M', 'Bremont, M', 'Greenberg, H B']",,,,
,PMC,Antibodies to varicella-zoster virus modulate antigen distribution but fail to induce viral persistence in vitro.,,PMC240458,,,"Varicella-zoster virus (VZV) persists in human sensory ganglia. One of the hypotheses to explain the induction or the maintenance of VZV latency is that it could be promoted by the immune response itself. It is known that in the case of viruses which bud off the infected cell membrane, virus-specific antibodies can induce antigenic modulation, i.e., spatial redistribution of viral antigens and modulation of their synthesis. To determine whether antigenic modulation occurs during VZV infection in vitro and could possibly be involved in viral persistence, we have grown infected cells in the presence of anti-VZV antibodies either transiently or permanently. The distribution of immune complexes and viral proteins was then analyzed. In transient immunomodulation experiments, the distribution of one or more viral antigens was modified not only in the cytoplasmic membranes but also in the cytoplasm and nucleoplasm of infected cells. When infected cells were kept permanently in the presence of antibodies, the same pattern of redistribution of immune complexes was observed and the localization of internal viral glycoproteins was significantly modified. However, antibodies did not prevent the lytic effect of infection; they altered neither the infectious virus yield nor the Western immunoblot pattern of viral proteins, suggesting that immunomodulation is not the primary effector of viral persistence.",,"['Sadzot-Delvaux, C', 'Marc, P', 'Lebon, L', 'Merville-Louis, M P', 'Piette, J', 'Rentier, B']",,,,
,PMC,Coronavirus species specificity: murine coronavirus binds to a mouse-specific epitope on its carcinoembryonic antigen-related receptor glycoprotein.,,PMC240449,,,"Like most coronaviruses, the coronavirus mouse hepatitis virus (MHV) exhibits strong species specificity, causing natural infection only in mice. MHV-A59 virions use as a receptor a 110- to 120-kDa glycoprotein (MHVR) in the carcinoembryonic antigen (CEA) family of glycoproteins (G. S. Dveksler, M. N. Pensiero, C. B. Cardellichio, R. K. Williams, G. S. Jiang, K. V. Holmes, and C. W. Dieffenbach, J. Virol. 65:6881-6891, 1991; and R. K. Williams, G. S. Jiang, and K. V. Holmes, Proc. Natl. Acad. Sci. USA 88:5533-5536, 1991). The role of virus-receptor interactions in determining the species specificity of MHV-A59 was examined by comparing the binding of virus and antireceptor antibodies to cell lines and intestinal brush border membranes (BBM) from many species. Polyclonal antireceptor antiserum (anti-MHVR) raised by immunization of SJL/J mice with BALB/c BBM recognized MHVR specifically in immunoblots of BALB/c BBM but not in BBM from adult SJL/J mice that are resistant to infection with MHV-A59, indicating a major difference in epitopes between MHVR and its SJL/J homolog which does not bind MHV (7). Anti-MHVR bound to plasma membranes of MHV-susceptible murine cell lines but not to membranes of human, cat, dog, monkey, or hamster cell lines. Cell lines from these species were resistant to MHV-A59 infection, and only the murine cell lines tested were susceptible. Pretreatment of murine fibroblasts with anti-MHVR prevented binding of radiolabeled virions to murine cells and prevented virus infection. Solid-phase virus-binding assays and virus overlay protein blot assays showed that MHV-A59 virions bound to MHVR on intestinal BBM from MHV-susceptible mouse strains but not to proteins on intestinal BBM from humans, cats, dogs, pigs, cows, rabbits, rats, cotton rats, or chickens. In immunoblots of BBM from these species, both polyclonal and monoclonal antireceptor antibodies that block MHV-A59 infection of murine cells recognized only the murine CEA-related glycoprotein and not homologous CEA-related glycoproteins of other species. These results suggest that MHV-A59 binds to a mouse-specific epitope of MHVR, and they support the hypothesis that the species specificity of MHV-A59 infection may be due to the specificity of the virus-receptor interaction.",,"['Compton, S R', 'Stephensen, C B', 'Snyder, S W', 'Weismiller, D G', 'Holmes, K V']",,,,
,PMC,N glycosylation of the virus binding domain is not essential for function of the human poliovirus receptor.,,PMC240442,,,"The human poliovirus receptor (hPVR) is a glycoprotein with three immunoglobulin-like extracellular domains, of which the N-terminal domain (V-type domain) is necessary and sufficient for virus binding and uptake. The effect of N glycosylation of the V domain of hPVR on binding and entry of poliovirus was studied. Stable mouse L-cell lines were generated that express PVR-specific cDNA. One of the cell lines expressed a mutant of hPVR, in which both asparagine residues of the two N-glycosylation sites of the V domain were changed to aspartate (N105D) and serine (N120S), respectively. In the second mutant cell line, the portion of the cDNA encoding the V domain of hPVR was substituted by the homologous sequence of the recently isolated PVR cDNA from monkey cells. This V domain naturally lacks both N glycosylation sites and encodes D105 and S120 at the respective positions of the open reading frame. Absence of N glycosylation at these sites was demonstrated by in vitro translation of the two mutant coding sequences in the presence of microsomal membranes. Both PVR mutant cell lines were capable of poliovirus binding and replication. However, binding of anti-PVR monoclonal antibody D171 and protection from viral replication by this antibody were observed only with the glycosylation mutant carrying the human V domain. In contrast, infection of the cell line expressing the monkey-human hybrid receptor was not blocked even though monkey cells are fully protected by monoclonal antibody D171. The data suggest that N glycosylation of the V domain of hPVR is not essential for viral replication in human tissues and that differential glycosylation of hPVR at these sites is likely not a determinant of viral tissue tropism. Furthermore, the virus binding site and the epitope recognized by monoclonal antibody D171 do not appear to overlap.",,"['Zibert, A', 'Wimmer, E']",,,,
,PMC,Characterization of lymphocytic choriomeningitis virus-binding protein(s): a candidate cellular receptor for the virus.,,PMC240431,,,"The attachment of lymphocytic choriomeningitis virus (LCMV) to murine and primate cell lines was quantitated by a fluorescence-activated cell sorter assay in which binding of biotinylated virus was detected with streptavidin-fluorescein isothiocyanate. Cell lines that were readily infected by LCMV (e.g., MC57, Rin, BHK, Vero, and HeLa) bound virus in a dose-dependent manner, whereas no significant binding was observed to lymphocytic cell lines (e.g., RMA and WIL 2) that were not readily infected. Binding was specific and competitively blocked by nonbiotinylated LCMV. It was also blocked by LCMV-specific antiserum and a neutralizing monoclonal antibody to the virus glycoprotein GP-1 but not by antibodies specific for GP-2, indicating that attachment was likely mediated by GP-1. Treatment of cells with any of several proteases abolished LCMV binding, whereas phospholipases including phosphatidylinositol-specific phospholipase C had no effect, indicating that one or more membrane proteins were involved in virus attachment. These proteins were characterized with a virus overlay protein blot assay. Virus bound to protein(s) with a molecular mass of 120 to 140 kDa in membranes from cell lines permissive for LCMV but not from nonpermissive cell lines. Binding was specific, since unlabeled LCMV, but not the unrelated enveloped virus herpes simplex virus type 1, competed with 125I-labeled LCMV for binding to the 120- to 140-kDa band. The proteinaceous nature of the LCMV-binding substance was confirmed by the lack of virus binding to proteinase K-treated membrane components. By contrast, glycosidase treatment of membranes did not abolish virus binding. However, in membranes treated with endoglycosidase F/N-glycosidase F, and/or neuraminidase and in membranes from cells grown in tunicamycin, the molecular mass of the LCMV-binding entity was reduced. Hence, LCMV attachment to rodent fibroblastic cell lines is mediated by a glycoprotein(s) with a molecular mass of 120 to 140 kDa, with complex N-linked sugars that are not involved in virus binding.",,"['Borrow, P', 'Oldstone, M B']",,,,
,PMC,The 5' end of the equine arteritis virus replicase gene encodes a papainlike cysteine protease.,,PMC240365,,,"The presence of a papainlike cysteine protease (PCP) domain in the N-terminal region of the equine arteritis virus (EAV) replicase, which had been postulated on the basis of limited sequence similarities with cellular and viral thiol proteases, was confirmed by in vitro translation and mutagenesis studies. The EAV protease was found to direct an autoproteolytic cleavage at its C terminus which leads to the production of an approximately 30-kDa N-terminal replicase product (nsp1) containing the PCP domain. Amino acid residues Cys-164 and His-230 of the EAV replicase polyprotein were identified as the most likely candidates for the role of PCP catalytic residues. By means of N-terminal sequence analysis of a PCP cleavage product, derived from a bacterial expression system, it was shown that cleavage occurs between Gly-260 and Gly-261. No evidence for PCP-directed cleavages at other positions in the EAV replicase was obtained. In cotranslational and posttranslational trans-cleavage assays, neither EAV nsp1 nor its precursor was able to process the PCP cleavage site in trans.",,"['Snijder, E J', 'Wassenaar, A L', 'Spaan, W J']",,,,
,PMC,The receptor for mouse hepatitis virus in the resistant mouse strain SJL is functional: implications for the requirement of a second factor for viral infection.,,PMC240321,,,"The SJL mouse strain is resistant to infection by some strains of the murine coronavirus mouse hepatitis virus (MHV), such as JHM and A59. The block to virus infection has been variously attributed to defects in virus receptors or virus spread. Since the cellular receptors for MHV, mmCGM1 and mmCGM2, have recently been identified as members of the carcinoembryonic antigen family, we reexamined the possible defectiveness of the MHV receptors in SJL mouse strain. Cloning and sequencing of the cDNAs of both mmCGMs RNAs from SJL mice revealed that they were identical in size to those of the susceptible C57BL/6 (B6) mouse. There was some sequence divergence in the N terminus of the mmCGM molecules between the two mouse strains, resulting in a different number of potential glycosylation sites. This was confirmed by in vitro translation of the mmCGM RNAs, which showed that the glycosylated mmCGM2 of SJL was smaller than that of B6 mice. However, transfection of either mmCGM1 or mmCGM2 from SJL mice into MHV-resistant Cos 7 cells rendered the cells susceptible to MHV infection. The ability of the SJL mmCGM molecules to serve as MHV receptors was comparable to that of those from B6. These molecules are expressed in SJL mouse brain and liver in a similar ratio and in amounts equivalent to those in the B6 mouse. Furthermore, we demonstrated that an SJL-derived cell line was susceptible to A59 but resistant to JHM infection. We concluded that the MHV receptor molecules in the SJL mouse are functional and that the resistance of SJL mice to infection by some MHV strains most likely results from some other factor(s) required for virus entry or some other step(s) in virus replication.",,"['Yokomori, K', 'Lai, M M']",,,,
,PMC,Biological control of chestnut blight: an example of virus-mediated attenuation of fungal pathogenesis.,,PMC372888,,,"Environmental concerns have focused attention on natural forms of disease control as potentially safe and effective alternatives to chemical pesticides. This has led to increased efforts to develop control strategies that rely on natural predators and parasites or that involve genetically engineered microbial pest control agents. This review deals with a natural form of biological control in which the virulence of a fungal pathogen is attenuated by an endogenous viral RNA genetic element: the phenomenon of transmissible hypovirulence in the chestnut blight fungus, Cryphonectria parasitica. Recent progress in the molecular characterization of a hypovirulence-associated viral RNA has provided an emerging view of the genetic organization and basic expression strategy of this class of genetic elements. Several lines of evidence now suggest that specific hypovirulence-associated virus-encoded gene products selectively modulate the expression of subsets of fungal genes and the activity of specific regulatory pathways. The construction of an infectious cDNA clone of a hypovirulence-associated viral RNA represents a major advancement that provides exciting new opportunities for examining the molecular basis of transmissible hypovirulence and for engineering hypovirulent strains for improved biocontrol. These developments have significantly improved the prospects of using this system to identify molecular determinants of virulence and elucidate signal transduction pathways involved in pathogenic responses. In addition, novel approaches are now available for extending the application of transmissible hypovirulence for management of chestnut blight and possibly other fungal diseases.",,"Nuss, D L",,,,
,PMC,Expression of antisense or sense RNA of an ankyrin repeat-containing gene blocks chloroplast differentiation in arabidopsis.,,PMC160243,,,"The Arabidopsis AKR gene that encodes a protein with four ankyrin repeats (a 33-amino acid motif that appears in the 89K domain of the human protein ankyrin) was isolated and characterized. A short sequence outside the ankyrin repeats is similar to that of the protein of the Drosophila muscle segment homeobox (msh) gene. The expression of the AKR gene is light dependent, and transgenic Arabidopsis plants with two or more copies of an antisense or sense AKR construct became chlorotic in a developmentally regulated manner. The chlorotic phenotype was genetically transmitted to the next generation, although most chlorotic plants produced much less seed. Reduced presence of thylakoid membranes and loss of grana are found in the plastids of chlorotic leaves, indicating that antisense or sense AKR has blocked chloroplast differentiation. This study indicates the importance of ankyrin repeat-containing proteins, not only in yeast and animals, but in plants as well.",,"['Zhang, H', 'Scheirer, D C', 'Fowle, W H', 'Goodman, H M']",,,,
,PMC,DNA rearrangement causes hepatocarcinogenesis in albumin-plasminogen activator transgenic mice.,,PMC50584,,,"Hepatocyte-directed production of urokinase-type plasminogen activator (uPA) in transgenic mice is hepatotoxic. Infrequently, hepatocytes arise that do not express uPA, due to physical loss of transgene DNA, and these cells clonally repopulate the entire liver within 3 months of birth. Surprisingly, hepatic tumors appear in these mice beginning at 8 months of age despite the fact that uPA is not oncogenic or genotoxic. Analysis of the transgene locus reveals that tumors arise only from a particular subclass of transgene-deficient cells in which the entire transgene array, and possibly a significant amount of flanking DNA, is deleted. Considering that all transgene-deficient regenerative nodules undergo extensive replication but only a subset gives rise to tumors, we propose that loss of genomic DNA, not mitogenesis per se, is a primary carcinogenic determinant in this model of hepatocarcinogenesis.",,"['Sandgren, E P', 'Palmiter, R D', 'Heckel, J L', 'Brinster, R L', 'Degen, J L']",,,,
,PMC,Evidence that the packaging signal for nodaviral RNA2 is a bulged stem-loop.,,PMC50506,,,"Flock house virus is an insect virus belonging to the family Nodaviridae; members of this family are characterized by a small bipartite positive-stranded RNA genome. The larger genomic segment, RNA1, encodes viral replication proteins, whereas the smaller one, RNA2, encodes coat protein. Both RNAs are packaged in a single particle. A defective-interfering RNA (DI-634), isolated from a line of Drosophila cells persistently infected with Flock house virus, was used to show that a 32-base region of RNA2 (bases 186-217) is required for packaging into virions. RNA folding analysis predicted that this region forms a stem-loop structure with a 5-base loop and a 13-base-pair bulged stem.",,"['Zhong, W', 'Dasgupta, R', 'Rueckert, R']",,,,
,PMC,The use of the nose to study the inflammatory response of the respiratory tract.,,PMC1021088,,,,,"['Persson, C G', 'Svensson, C', 'Greiff, L', 'Anderson, M', 'Wollmer, P', 'Alkner, U', 'Erjefält, I']",,,,
,PMC,Porcine respiratory coronavirus in Quebec: Serological studies using a competitive inhibition enzyme-linked immunosorbent assay,,PMC1481437,,,"Porcine respiratory coronavirus (PRCV) was identified for the first time in Quebec, using a blocking enzyme-linked immunosorbent assay (ELISA). Unlike the virus neutralization test (VNT), this ELISA was able to distinguish transmissible gastroenteritis virus (TGEV) from PRCV. Among the 15 seropositive fattening herds from group A, sera containing PRCV antibodies represented 74.8%, whereas those with TGEV antibodies represented only 7.2%. In group B, which consisted of 15 sow herds, nine herds expressed only PRCV-specific antibodies while the other herds had animals positive for TGEV-specific antibodies.",,"['Jabrane, Ahmed', 'Elazhary, Youssef', 'Talbot, Brian G.', 'Ethier, Raymond', 'Dubuc, Claude', 'Assaf, Robert']",,,,
,PMC,Genetic recombination in brome mosaic virus: effect of sequence and replication of RNA on accumulation of recombinants.,,PMC240186,,,"In order to facilitate the isolation of recombinants in brome mosaic virus, a series of duplication mutants with alterations in the RNA3 3' noncoding region has been engineered. The distribution of crossovers, which was observed to be dependent on the parental RNA3 sequence, supported the role of RNA structure in recombination. However, a negative correlation between replication of the parental RNA3 constructs and the accumulation of recombinant progeny confirmed the role of selection.",,"['Nagy, P D', 'Bujarski, J J']",,,,
,PMC,"Identification of T-cell epitopes on E2 protein of rubella virus, as recognized by human T-cell lines and clones.",,PMC240179,,,"T-cell epitopes on the E2 protein of rubella virus were studied by using 15 overlapping synthetic peptides covering the E2 protein sequence. The most frequently recognized epitopes on E2 were E2-4 (residues 54 to 74), with 5 of 10 tested T-cell lines responding to it. Two CD4+ cytotoxic T-cell cloned isolated from one T-cell line responded strongly in proliferation assays with peptide E2-4 and were cytotoxic to target cells presenting the E2-4 determinant. Truncated peptides contained within the E2-4 peptide sequence were used to define the T-cell determinants. Results indicated that amino acid residues 54 to 65 were directly involved. Human cell lines with different HLA phenotypes were tested for the capacity to present the antigenic determinants. The results suggested that recognition of peptide E2-4 by T-cell clones was associated with HLA DR7.",,"['Ou, D', 'Chong, P', 'Choi, Y', 'McVeigh, P', 'Jefferies, W A', 'Koloitis, G', 'Tingle, A J', 'Gillam, S']",,,,
,PMC,Monoclonal antibody analysis of neutralization and antibody-dependent enhancement of feline infectious peritonitis virus.,,PMC240165,,,"Fifty-four monoclonal antibodies (MAbs) to feline infectious peritonitis virus (FIPV) were characterized according to protein specificity, immunoglobulin subclass, virus neutralization, reactivity with different coronaviruses, and ability to induce antibody-dependent enhancement (ADE) of FIPV infection in vitro. The MAbs were found to be specific for one of three structural proteins of FIPV. A total of 47 MAbs were specific for the 205-kDa spike protein (S), 3 MAbs were specific for the 45-kDa nucleocapsid protein (N), and 4 MAbs were specific for the 26- to 28-kDa membrane protein (M). The S-specific MAbs showed various degrees of cross-reactivity with strains of FIPV, feline enteric coronavirus, canine coronavirus, and porcine transmissible gastroenteritis virus. Nineteen S-specific MAbs neutralized FIPV. A total of 15 of the neutralizing MAbs induced ADE, and all but 1 were of the immunoglobulin G2a subclass. The remaining four neutralizing MAbs that did not induce ADE were of the immunoglobulin G1 subclass. Two S-specific MAbs induced ADE but were nonneutralizing. None of the N- or M-specific MAbs was neutralizing or induced ADE. On the basis of the reactivity patterns of the MAbs with FIPV and related coronaviruses, it was concluded that there is a minimum of five neutralizing sites on S. In most instances, neutralizing MAbs were able to induce ADE, demonstrating a direct relationship between neutralization and enhancement. The difference in immunoglobulin subclass between neutralizing MAbs that induced ADE and those that did not induce ADE suggests that there may be a restriction in the immunoglobulin subclasses capable of mediating ADE.",,"['Corapi, W V', 'Olsen, C W', 'Scott, F W']",,,,
,PMC,Epitope specificity of protective lactogenic immunity against swine transmissible gastroenteritis virus.,,PMC240143,,,"The epitope specificity of the protective immune response against swine transmissible gastroenteritis (TGE) has been investigated by using circulating and secretory antibodies. This study was carried out with sows vaccinated with TGEV or the antigenically related porcine respiratory coronavirus (PRCV). TGEV vaccination of sows resulted in greater lactogenic protection of suckling piglets against TGEV challenge and a higher secretory immune response than PRCV vaccination did. These differences in the immune response were conditioned by the route of antigen presentation as a result of the different tropism of each virus. Epitopes on S protein, and in particular those contained in its antigenic site. A, were more immunogenic than epitopes on N and M proteins in both groups of vaccinated sows, as determined by a competitive radioimmunoassay. Minor differences in antibody response against the previously defined antigenic subsites Aa, Ab, and Ac were also detected, with subsite Ab being the most antigenic in both TGEV- and PRCV-immune sows. These findings suggest that antigenic site A on S protein, involved in virus neutralization, is the immunodominant site in pregnant sows that confer lactogenic protection. They also validate, in experiments with secretory antibodies, the antigenic maps made with murine monoclonal antibodies. Therefore, this antigenic site should be considered for vaccine or diagnostic development.",,"['De Diego, M', 'Laviada, M D', 'Enjuanes, L', 'Escribano, J M']",,,,
,PMC,Mutagenic analysis of the coronavirus intergenic consensus sequence.,,PMC240125,,,"Previously, a system in which an intergenic region from mouse hepatitis virus (MHV) inserted into an MHV defective interfering (DI) RNA led to transcription of a subgenomic DI RNA in helper virus-infected cells was established. In the present study, a DI cDNA containing one UCUAAAC consensus sequence in the middle of the 0.3-kb-long intergenic region located between genes 6 and 7 was constructed. From this DI cDNA clone, 21 mutant DI RNAs were constructed so that each of the seven consensus sequence nucleotides was changed individually to the three alternative bases. These mutants were used to define how changes in the integrity of MHV transcription consensus sequence UCUAAAC affected mRNA transcription. Except for two mutants with the sequences UGUAAAC and UCGAAAC, all of the mutants supported efficient subgenomic DI RNA transcription. This indicated that MHV transcription regulation was sufficiently flexible to recognize altered consensus sequences. Next, these and other mutants were used to examine the leader-body fusion site on the subgenomic DI RNAs. Sequence analysis demonstrated that all subgenomic DI RNAs analyzed contained two pentanucleotide sequences; the first sequence seemed to be contributed by the leader, and the leader-body fusion most likely took place at either the first or the second nucleotide of the second sequence. This observation was not consistent with the proposed coronavirus transcription model (S. C. Baker and M. M. C. Lai, EMBO J. 9:4173-4179, 1990) which states that nucleotide mismatch can be corrected by RNA polymerase proofreading activity.",,"['Joo, M', 'Makino, S']",,,,
,PMC,Structural proteins of equine arteritis virus.,,PMC240121,,,"We have recently shown that the genome of equine arteritis virus (EAV) contains seven open reading frames (ORFs). We now present data on the structural proteins of EAV and the assignment of their respective genes. Virions are composed of a 14-kDa nucleocapsid protein (N) and three membrane proteins designated M, GS, and GL. M is an unglycosylated protein of 16 kDa, and GS and GL are N-glycosylated proteins of 25 and 30 to 42 kDa, respectively. The broad size distribution of GL results from heterogeneous N-acetyllactosamine addition since it is susceptible to digestion by endo-beta-galactosidase. Using monospecific antisera as well as an antivirion serum, and by expression of individual ORFs, the genes for the structural proteins were identified: ORF 7 codes for N, ORF 6 for M, ORF 5 for GL, and ORF 2 for GS. With the exception of GS, the proteins are about equally abundant in EAV virions, being present at a molar ratio of 3 (N):2 (M):3 (GL). The GS protein, which is expressed at a level similar to that of M in infected cells, is strikingly underrepresented in virus particles (1 to 2%). Our data justify a distinct taxonomic position for EAV, together with lactate dehydrogenase-elevating virus and simian hemorrhagic fever virus; although coronavirus- and toroviruslike in features of transcription and translation, the virion architecture of EAV is fundamentally different.",,"['de Vries, A A', 'Chirnside, E D', 'Horzinek, M C', 'Rottier, P J']",,,,
,PMC,New nucleotide sequence data on the EMBL File Server.,,PMC334375,,,,,,,,,
,PMC,Mouse hepatitis virus utilizes two carcinoembryonic antigens as alternative receptors.,,PMC283671,,,"The cellular receptor for the murine coronavirus mouse hepatitis virus (MHV) has been identified as a member of the murine carcinoembryonic antigen (CEA) family (R. K. Williams, G. S. Jiang, and K. V. Holmes, Proc. Natl. Acad. Sci. USA 88:5533-5536, 1991). However, the receptor protein was not detected in some of the susceptible mouse tissues. We therefore examined whether other types of MHV receptor might exist. By polymerase chain reaction with the conserved sequences of murine CEA gene family members (mmCGM) as primers, we detected two CEA-encoding RNAs in the mouse liver. One of them (1.3 kb) encodes mmCGM1, which has previously been identified as the receptor for MHV, and the other one (0.8 kb) was shown to encode another member of mouse CGM, mmCGM2. The sequence analysis showed that mmCGM2 lacks 564 nucleotides in the middle of the gene compared with mmCGM1. These two CEA transcripts are probably derived from the same gene by an alternative splicing mechanism. Expression of either of these cDNA clones in COS-7 cells rendered these cells susceptible to MHV infection, suggesting that not only mmCGM1 but also mmCGM2 serves as a receptor for MHV. The mmCGM2 was the major CEA species in the mouse brain, which is a main target organ for the neurotropic strains of MHV. Very little mmCGM1 was detected in the mouse brain or in cells of the susceptible mouse astrocytoma cell line DBT. This result indicates that MHV may utilize different CEA molecules as the major receptor in the mouse brain and in the liver. This is a first identification of multiple receptors for a single virus. The presence of different receptors in different tissues may explain the target cell specificity of certain MHVs.",,"['Yokomori, K', 'Lai, M M']",,,,
,PMC,Internal entry of ribosomes on a tricistronic mRNA encoded by infectious bronchitis virus.,,PMC241492,,,"mRNA3 specified by the coronavirus infectious bronchitis virus appears to be functionally tricistronic, having the capacity to encode three small proteins (3a, 3b, and 3c) from separate open reading frames (ORFs). The mechanism by which this can occur was investigated through in vitro translation studies using synthetic mRNAs containing the 3a, 3b, and 3c ORFs, and the results suggest that translation of the most distal of the three ORFs, that for 3c, is mediated by an unconventional, cap-independent mechanism involving internal initiation. This conclusion is based on several observations. A synthetic mRNA whose peculiar 5' end structure prevents translation of the 5'-proximal ORFs (3a and 3b) directs the synthesis of 3c normally. Translation of 3c, unlike that of 3a and 3b, was insensitive to the presence of the 5' cap analog 7-methyl-GTP, and it was unaffected by alteration of the sequence contexts for initiation on the 3a and 3b ORFs. Finally, an mRNA in which the 3a/b/c infectious bronchitis virus coding region was placed downstream of the influenza A virus nucleocapsid protein gene directed the efficient synthesis of 3c as well as nucleocapsid protein, whereas initiation at 3a and 3b could not be detected. Expression of the 3c ORF from this mRNA, however, was abolished when the 3a and 3b coding region was deleted, indicating that 3c initiation is dependent on upstream sequence elements which together may serve as a ribosomal internal entry site similar to those described for picornaviruses.",,"['Liu, D X', 'Inglis, S C']",,,,
,PMC,RNA recombination in a coronavirus: recombination between viral genomic RNA and transfected RNA fragments.,,PMC241489,,,"Mouse hepatitis virus (MHV), a coronavirus, has been shown to undergo a high frequency of RNA recombination both in tissue culture and in animal infection. So far, RNA recombination has been demonstrated only between genomic RNAs of two coinfecting viruses. To understand the mechanism of RNA recombination and to further explore the potential of RNA recombination, we studied whether recombination could occur between a replicating MHV RNA and transfected RNA fragments. We first used RNA fragments which represented the 5' end of genomic-sense sequences of MHV RNA for transfection. By using polymerase chain reaction amplification with two specific primers, we were able to detect recombinant RNAs which incorporated the transfected fragment into the 5' end of the viral RNA in the infected cells. Surprisingly, even the anti-genomic-sense RNA fragments complementary to the 5' end of MHV genomic RNA could also recombine with the MHV genomic RNAs. This observation suggests that RNA recombination can occur during both positive- and negative-strand RNA synthesis. Furthermore, the recombinant RNAs could be detected in the virion released from the infected cells even after several passages of virus in tissue culture cells, indicating that these recombinant RNAs represented functional virion RNAs. The crossover sites of these recombinants were detected throughout the transfected RNA fragments. However, when an RNA fragment with a nine-nucleotide (CUUUAUAAA) deletion immediately downstream of a pentanucleotide (UCUAA) repeat sequence in the leader RNA was transfected into MHV-infected cells, most of the recombinants between this RNA and the MHV genome contained crossover sites near this pentanucleotide repeat sequence. In contrast, when exogenous RNAs with the intact nine-nucleotide sequence were used in similar experiments, the crossover sites of recombinants in viral genomic RNA could be detected at more-downstream sites. This study demonstrated that recombination can occur between replicating MHV RNAs and RNA fragments which do not replicate, suggesting the potential of RNA recombination for genetic engineering.",,"['Liao, C L', 'Lai, M M']",,,,
,PMC,Transposition of a Ty3 GAG3-POL3 fusion mutant is limited by availability of capsid protein.,,PMC241485,,,"Ty3 encodes structural proteins in its upstream open reading frame (GAG3) and catalytic proteins in an overlapping open reading frame (POL3). As is the case for retroviruses, high levels of structural protein versus catalytic proteins are synthesized and we show here that catalytic proteins are derived from a GAG3-POL3 fusion polyprotein. To evaluate the relative contributions of structural and catalytic components of the Ty3 particle, we perturbed the balance of these proteins by fusing the GAG3 and POL3 frames. This fusion Ty3 was capable of complementing low levels of transposition of a donor Ty3 which contained only cis-acting sequences required for transposition. Examination of extracts of cells expressing the GAG3-POL3 fusion mutant showed that particle formation differed qualitatively and quantitatively from viruslike particle formation by wild-type Ty3. Suprisingly, expression of 238 codons of GAG3, encoding only capsid protein, complemented transposition and particle formation defects of the fusion mutant, showing that the limiting deficiency was in capsid, and not in nucleocapsid, function. In addition, protein containing the capsid domain expressed alone accumulated in the same particulate fraction as viruslike particles, showing that it was sufficient for particle formation. The activity of the Ty3 fusion mutant contrasts with the inviability of mutant retroviruses in which gag and pol frames were fused and argues that retrotransposons tolerate considerable variation in the nucleoprotein complexes that permit replication and integration.",,"['Kirchner, J', 'Sandmeyer, S B', 'Forrest, D B']",,,,
,PMC,The fitness of defective interfering murine coronavirus DI-a and its derivatives is decreased by nonsense and frameshift mutations.,,PMC241466,,,"The genome of the defective interfering (DI) mouse hepatitis virus DI-a carries a large open reading frame (ORF) consisting of ORF1a, ORF1b, and nucleocapsid sequences. To test whether this fusion ORF is important for DI virus replication, we constructed derivatives of the DI-a genome in which the reading frame was truncated by a nonsense codon or a frameshift mutation. In vitro-transcribed DI RNAs were transfected into mouse hepatitis virus-infected cells followed by undiluted passage of the resulting virus-DI virus stocks. The following observations were made. (i) Truncation of the fusion ORF was not lethal but led to reduced accumulation of DI RNA. (ii) When pairs of nearly identical in-frame and out-of-frame DI RNAs were directly compared by cotransfection, DI viruses containing in-frame genomic RNAs prevailed within three successive passage even when the out-of-frame RNAs were transfected in 10-fold molar excess. (iii) When DI viruses containing out-of-frame genomic RNAs were passaged, mutants emerged and were selected for that had restored the reading frame. We conclude that translation of the fusion ORF is indeed required for efficient propagation of DI-a and its derivatives.",,"['de Groot, R J', 'van der Most, R G', 'Spaan, W J']",,,,
,PMC,Deletions in the hepatitis B virus small envelope protein: effect on assembly and secretion of surface antigen particles.,,PMC241459,,,"The small envelope S protein of hepatitis B virus carrying the surface antigen has the unique property of mobilizing cellular lipids into empty envelope particles which are secreted from mammalian cells. We studied the biogenesis of such particles using site-directed mutagenesis. In this study, we describe the effect of deletions in the N-terminal hydrophobic and hydrophilic domains of the S protein. Whereas short overlapping deletions of hydrophilic sequences flanking the first hydrophobic domain were tolerated, larger deletions of the same sequences were not. Conversely, the hydrophilic region preceding the second hydrophobic domain was not permissive for even short deletions. Deletion of part or all of the first hydrophobic domain also completely blocked secretion, confirming that the entire apolar region serves an essential function. Most of the secretion-defective deletion mutants still entered the secretory pathway and translocated at least the second hydrophilic domain across the membrane of the endoplasmic reticulum. These mutants appeared to remain arrested in a membrane-associated configuration in the endoplasmic reticulum or the cis-Golgi compartment but preserved their capacity for oligomerization with the wild-type S protein. While secretion of wild-type S protein was specifically blocked by the formation of intracellularly retained mixed envelope aggregates, secretion of an unrelated protein (interleukin 9) was completely unaffected.",,"['Prange, R', 'Nagel, R', 'Streeck, R E']",,,,
,PMC,Monoclonal anti-idiotypes induce neutralizing antibodies to enterovirus 70 conformational epitopes.,,PMC241449,,,"Monoclonal antibodies (MAbs) directed against the prototype enterovirus 70 (EV-70) strain J670/71 were generated and characterized in order to produce anti-idiotypic MAbs (MAb2s) for use as surrogate immunogens. Western immunoblot and radioimmunoprecipitation assays suggested that all the MAbs recognize conformational epitopes on the virion surface. An EV-70-neutralizing antibody, MAb/ev-12 (MAb1), was selected for the production of MAb2s. Five MAb2s were selected for their capacities to inhibit the interaction of MAb/ev-12 with EV-70 in dot immunobinding inhibition and immunofluorescence assays. In addition, these five MAb2s inhibited virus neutralization mediated by MAb/ev-12, suggesting that they recognize paratope-associated idiotopes. In competition enzyme immunosorbent assays, none of the five MAb2s recognized other neutralizing and nonneutralizing EV-70-specific MAbs, demonstrating that the MAb2s were specific for private idiotopes. Immunization with each of the MAb2s was carried out for the production of anti-anti-idiotypic antibodies (Ab3). All five MAb2s induced an immune response. Moreover, results suggested that they share idiotopes, since MAb2-MAb/ev-12 binding could be inhibited by homologous as well as heterologous Ab3s. Ab3 sera were shown to possess antibodies capable of immunoprecipitating 35S-labeled viral proteins in the same manner as MAb/ev-12. Nine of 15 mice immunized with MAb2s demonstrated Ab3 neutralizing activity specific for the prototype EV-70 strain, J670/71. The potential application of MAb2s to serve as surrogate immunogens for conformational epitopes is substantiated by the results presented in this report.",,"['Wiley, J A', 'Hamel, J', 'Brodeur, B R']",,,,
,PMC,Ribosomal movement impeded at a pseudoknot required for frameshifting.,,PMC49975,,,"Translational frameshifting sometimes occurs when ribosomes encounter a ""shift"" site preceding a region of unusual secondary structure, which in at least three cases is known to be a pseudoknot. We provide evidence that ribosomes have a decreased rate of movement through a pseudoknot required for frameshifting. These paused ribosomes are directly situated over the shift sequence. Ribosomal pausing appears to be necessary but not sufficient for frameshifting.",,"['Tu, C', 'Tzeng, T H', 'Bruenn, J A']",,,,
,PMC,New nucleotide sequence data on the EMBL File Server.,,PMC334213,,,,,,,,,
,PMC,Hematopoietic target cells of anemogenic subgroup C versus nonanemogenic subgroup A feline leukemia virus.,,PMC289115,,,"Feline leukemia viruses (FeLVs) belonging to interference subgroup C induce fatal anemia resembling human pure red cell aplasia (PRCA). Subgroup A FeLVs, although closely related genetically to FeLVs of subgroup C, do not induce PRCA. The determinants for PRCA induction by a molecularly cloned prototype subgroup C virus (FeLV-Sarma-C [FSC]) have been localized to the N-terminal 241 amino acids of the surface glycoprotein (SU) gp70. To investigate whether the anemogenic activity of FSC reflects a unique capacity to infect erythroid progenitor cells, we used correlative immunogold, immunofluorescence, and cytological staining to study prospectively the hemopoietic cell populations infected by either FSC or FeLV-FAIDS-61E-A (F6A), a prototype of subgroup A virus. The results demonstrated that although only FSC-infected animals developed erythrocyte aplasia, the env SU and the major core protein (p27) were expressed in a surprisingly large fraction of the lymphoid, erythroid, and myeloid lineage marrow cells in both FSC- and F6A-infected cats. Between days 8 and 17 postinoculation, gp70 and p27 were detected in 43 to 73% of erythroid, 25 to 75% of lymphoid, and 35 to 50% of myeloid lineage cells, regardless of whether the cats were infected with FSC or F6A. Thus, anemogenic subgroup C and nonanemogenic subgroup A FeLVs have similar hemopoietic cell tropism and infection kinetics, despite their divergent effects on erythroid progenitor cell function. Acute anemia induction by subgroup C FeLV, therefore, does not reflect a unique tropism for marrow erythroid cells but rather indicates a unique cytopathic effect of the SU on erythroid progenitor cells.",,"['Dean, G A', 'Groshek, P M', 'Mullins, J I', 'Hoover, E A']",,,,
,PMC,Induction of feline immunodeficiency virus-specific cytolytic T-cell responses from experimentally infected cats.,,PMC289097,,,"We have examined the in vitro induction and activity of feline immunodeficiency virus (FIV)-specific cytolytic T cells obtained from cats experimentally infected for 7 to 17 weeks or 20 to 22 months with the Petaluma isolate of FIV. Normal or FIV-infected autologous and allogeneic T lymphoblastoid cells were used as target cells in chromium-51 or indium-111 release assays. When effector cells consisted of either fresh peripheral blood mononuclear cells or concanavalin A- and interleukin-2-stimulated cells, only low levels of cytotoxicity were observed. However, the levels of FIV-specific cytotoxicity were consistently higher in both groups of cats following in vitro stimulation of the effector cells with irradiated, FIV-infected autologous T lymphoblastoid cells and interleukin-2. The effector cells lysed autologous but not allogeneic FIV-infected target cells and were composed predominantly of CD8+ T cells, indicating that the FIV-specific cytotoxicity measured in this system is mediated by CD8+, major histocompatibility complex class I-restricted T cells. These studies show that FIV-specific cytolytic T cells can be detected as early as 7 to 9 weeks postinfection, and they define a system to identify virus-encoded epitopes important in the induction of protective immunity against lentiviruses.",,"['Song, W', 'Collisson, E W', 'Billingsley, P M', 'Brown, W C']",,,,
,PMC,Canine and feline host ranges of canine parvovirus and feline panleukopenia virus: distinct host cell tropisms of each virus in vitro and in vivo.,,PMC289096,,,"Canine parvovirus (CPV) emerged as an apparently new virus during the mid-1970s. The origin of CPV is unknown, but a variation from feline panleukopenia virus (FPV) or another closely related parvovirus is suspected. Here we examine the in vitro and in vivo canine and feline host ranges of CPV and FPV. Examination of three canine and six feline cell lines and mitogen-stimulated canine and feline peripheral blood lymphocytes revealed that CPV replicates in both canine and feline cells, whereas FPV replicates efficiently only in feline cells. The in vivo host ranges were unexpectedly complex and distinct from the in vitro host ranges. Inoculation of dogs with FPV revealed efficient replication in the thymus and, to some degree, in the bone marrow, as shown by virus isolation, viral DNA recovery, and Southern blotting and by strand-specific in situ hybridization. FPV replication could not be demonstrated in mesenteric lymph nodes or in the small intestine, which are important target tissues in CPV infection. Although CPV replicated well in all the feline cells tested in vitro, it did not replicate in any tissue of cats after intramuscular or intravenous inoculation. These results indicate that these viruses have complex and overlapping host ranges and that distinct tissue tropisms exist in the homologous and heterologous hosts.",,"['Truyen, U', 'Parrish, C R']",,,,
,PMC,Proteolytic cleavage of the reovirus sigma 3 protein results in enhanced double-stranded RNA-binding activity: identification of a repeated basic amino acid motif within the C-terminal binding region.,,PMC289090,,,"The reovirus capsid protein sigma 3 was examined for double-stranded RNA (dsRNA)-binding activity by Northwestern (RNA-protein) blot analysis. Treatment of virion-derived sigma 3 protein with Staphylococcus aureus V8 protease led to an increase in the dsRNA-binding activity associated with the C-terminal fragment of the protein. Recombinant C-terminal fragments of the sigma 3 protein were expressed in Escherichia coli from the S4 cDNA of reovirus serotype 1. These truncated sigma 3 proteins displayed proteolytic processing and dsRNA-binding activity similar to those observed for native, virion-derived sigma 3 protein as measured by Northwestern blot analysis. Construction of a modified pET3c vector, pET3Exo, allowed the production of 3'-terminal deletions of the S4 cDNA by using exonuclease III and rapid screening of the induced truncated sigma 3 proteins. An 85-amino-acid domain within the C-terminal portion of the sigma 3 protein which was responsible for dsRNA-binding activity was identified. The 85-amino-acid domain possessed a repeated basic amino acid motif which was conserved in all three serotypes of reovirus. Deletion of one of the basic motifs, predicted to be an amphipathic alpha-helix, destroyed dsRNA-binding activity.",,"['Miller, J E', 'Samuel, C E']",,,,
,PMC,The nucleocapsid protein gene of bovine coronavirus is bicistronic.,,PMC289081,,,"For animal RNA viruses that replicate through an RNA intermediate, reported examples of bicistronic mRNAs with overlapping open reading frames in which one cistron is contained entirely within another have been made only for those with negative-strand or double-stranded genomes. In this report, we demonstrate for the positive-strand bovine coronavirus that an overlapping open reading frame potentially encoding a 23-kDa protein (names the I [for internal open reading frame] protein) and lying entirely within the gene for the 49-kDa nucleocapsid phosphoprotein is expressed during virus replication from a single species of unedited mRNA. The I protein was specifically immunoprecipitated from virus-infected cells with an I-specific antipeptide serum and was shown to be membrane associated. Many features of I protein synthesis conform to the leaky ribosomal scanning model for regulation of translation. This, to our knowledge, is the first example of a bicistronic mRNA for a cytoplasmically replicating, positive-strand animal RNA virus in which one cistron entirely overlaps another.",,"['Senanayake, S D', 'Hofmann, M A', 'Maki, J L', 'Brian, D A']",,,,
,PMC,Second-site suppressor mutations assist in studying the function of the 3' noncoding region of turnip yellow mosaic virus RNA.,,PMC289071,,,"The 3' noncoding region of turnip yellow mosaic virus RNA includes an 82-nucleotide-long tRNA-like structure domain and a short upstream region that includes a potential pseudoknot overlapping the coat protein termination codon. Genomic RNAs with point mutations in the 3' noncoding region that result in poor replication in protoplasts and no systemic symptoms in planta were inoculated onto Chinese cabbage plants in an effort to obtain second-site suppressor mutations. Putative second-site suppressor mutations were identified by RNase protection and sequencing and were then introduced into genomic cDNA clones to permit their characterization. A C-57----U mutation in the tRNA-like structure was a strong suppressor of the C-55----A mutation which prevented both systemic infection and in vitro valylation of the viral RNA. Both of these phenotypes were rescued in the double mutant. An A-107----C mutation was a strong second-site suppressor of the U-96----G mutation, permitting the double mutant to establish systemic infection. The C-107 and G-96 mutations are located on opposite strands of one helix of a potential pseudoknot, and the results support a functional role for the pseudoknot structure. A mutation near the 5' end of the genome (G + 92----A), at position -3 relative to the initiation codon of the essential open reading frame 206, was found to be a general potentiator of viral replication, probably as a result of enhanced expression of open reading frame 206. The A + 92 mutation enhanced the replication of mutant TYMC-G96 in protoplasts but was not a sufficiently potent suppressor to permit systemic spread of the A + 92/G-96 double mutant in plants.",,"['Tsai, C H', 'Dreher, T W']",,,,
,PMC,Enhancement of ribosomal frameshifting by oligonucleotides targeted to the HIV gag-pol region.,,PMC334071,,,"The pol gene of all retroviruses is expressed as a gag-pol fusion protein which is proteolytically processed to produce all viral enzymes. In the human immunodeficiency virus (HIV), the gag and pol genes overlap by 241 nucleotides with pol in the -1 phase with respect to gag. The gag-pol fusion is produced via a -1 ribosomal frameshifting event that brings the overlapping, out-of-phase gag and pol genes into translational phase. Frameshifting occurs at a so called 'shift site' 8-10 nucleotides upstream of a hairpin loop which may play a role in the regulation of frameshifting. We have fused this region of HIV-1 to the 5' end of the firefly luciferase reporter gene in order to quantitatively measure ribosomal frameshifting both in cells and by in vitro translation. A series of 2'-O-methyl oligonucleotides was designed to specifically bind the sequences which flank the gag-pol hairpin. Ribosomal frameshifting is enhanced up to 6 fold by those oligonucleotides which bind the area just 3 to the stem. Oligonucleotides which bind 5' to the stem have no effect on frameshift efficiency. In addition, we have constructed a series of fusion genes which mimic the effect of the bound oligonucleotides with intramolecular hairpins. The results suggest that increasing RNA secondary structure downstream of the shift site increases the frequency of ribosomal frameshifting, and that this effect can be mimicked by antisense oligonucleotides.",,"['Vickers, T A', 'Ecker, D J']",,,,
,PMC,Breast Milk: A vital defense against infection,,PMC2145744,,,"The protective agents in colostrum and mature breast milk include specific antibodies, enzymes, leukocytes and their products, antibinding factors, antiviral factors, promoters of a protective intestinal microflora, and immune stimulators. These agents persist through the length of the infant's digestive tract, are unaffected by gastric acid and digestive enzymes, are present throughout lactation, and protect by noninflammatory mechanisms.",,"Joneja, Janice M. Vickerstaff",,,,
,PMC,Experimental autoimmune uveoretinitis (EAU) versus experimental allergic encephalomyelitis (EAE): a comparison of T cell-mediated mechanisms.,,PMC1554436,,,"EAU is a model of ocular inflammatory disease. EAU resembles another T cell-mediated autoimmune disease--experimental allergic encephalomyelitis--since both have increased expression of MHC class II molecules in the target tissue, can be adoptively transferred by activated CD4+ T cells and are inhibited by cyclosporin A. The immunological findings will be compared to find out if the same cellular mechanisms are involved in both diseases.",,"['Calder, V L', 'Lightman, S L']",,,,
,PMC,Gastrointestinal symptoms in patients infected with human immunodeficiency virus: relevance of infective agents isolated from gastrointestinal tract.,,PMC1379446,,,"The correlation of gastrointestinal symptoms and infections in 186 consecutive patients with human immunodeficiency virus (HIV) infection undergoing diagnostic endoscopy (oesophagogastroduodenoscopy, n = 124; colonoscopy, n = 37; both, n = 25) was investigated. Biopsy and stool samples were examined for infective agents. Only weight loss (p = 0.003) and dysphagia (p = 0.027) were more common in patients at stage CDC IV compared with earlier stages. In three of 27 patients at stage II/III and in 93 of 159 patients at stage IV an infective agent was identified in stool or gastrointestinal biopsy specimen (p < 0.001). Cytomegalovirus (n = 35), Candida sp (n = 28), M avium complex (n = 10), and Cryptosporidium (eight) were the most frequent agents detected. At stage IV, diarrhoea was more frequent in infected compared with non-infected patients (p = 0.006); however, an infective agent was also found in 39 of 82 patients at stage IV without diarrhoea. The frequency of gastrointestinal symptoms was not consistently increased in patients harbouring specific infective agents compared with non-infected patients. Our findings indicate that the pathogenic relevance of a gastrointestinal infection in HIV infected patients has to be verified and indirectly support the existence of an HIV associated enteropathy.",,"['Ullrich, R', 'Heise, W', 'Bergs, C', ""L'age, M"", 'Riecken, E O', 'Zeitz, M']",,,,
,PMC,"Inhibition of the serine/threonine protein phosphatases PP1 and PP2A in lymphocytes: effect on mRNA levels for interleukin-2, IL-2R alpha, krox-24, p53, hsc70 and cyclophilin.",,PMC1421563,,,"Lymphocyte activation requires signal transduction mediated by reversible phosphorylation. Changing profiles of phosphorylated intermediates relate to the progressive series of transduction pathways in cells moving from G0 to G1, and thereafter through the cell cycle. We have previously shown that transient inhibition of the serine/threonine protein phosphatases PP1 and PP2A by okadaic acid enhances early mitogenic stimulation. Thus target proteins of PP1/PP2A may be involved in regulation of early mitogenic signalling, with the phosphorylated form(s) being associated with signal enhancement. Later, pathways require dephosphorylation of these proteins, since continuous treatment with okadaic acid blocks lymphocyte progression through the cell cycle. Delayed addition of okadaic acid showed that this blockade occurs between 8 and 24 hr. Here we have furthered these observations to the level of gene induction by measuring messenger RNA (mRNA) levels for the following proteins: interleukin-2 (IL-2) and IL-2R alpha; p53, a tumour suppressor protein; the transcription factor krox-24; and two mediators of protein folding, namely cyclophilin and the heat-shock protein hsc70. An external standard was used to quantitate the mRNA levels per cell. We found that 24 hr exposure to okadaic acid has a general suppressive effect on concanavalin A (Con A)-stimulated gene induction. However, at 4 hr okadaic acid enhanced IL-2 mRNA levels induced by Con A. Moreover, in unstimulated lymphocytes, okadaic acid caused the induction of krox-24, indicating a role for PP1 and PP2A in the regulation of this gene in resting cells.",,"['Richards, F M', 'Milner, J', 'Metcalfe, S']",,,,
,PMC,Presence of parasite antigen on the surface of P388D1 cells infected with Ehrlichia risticii.,,PMC257284,,,"Indirect immunofluorescence staining of macrophages infected with Ehrlichia risticii by anti-E. risticii serum revealed a punctate staining pattern on the surface of the host cell. This pattern was distinguishable by fluorescence microscopy from E. risticii bound to the surface of the macrophage and from intracellular E. risticii. The surface localization of ehrlichial antigen on infected macrophages was confirmed by electron microscopy with immunoferritin labeling. As the intracellular ehrlichial burden increased, the amount of ehrlichial antigen on the host cell surface increased. Prokaryotic protein synthesis was necessary for the maintenance of ehrlichial antigen on the host cell surface, as demonstrated by disappearance of the surface antigen following treatment with oxytetracycline. However, host cell protein synthesis was not required, as demonstrated by the continued presence of ehrlichial antigen on the surface of host cells after cycloheximide treatment. Pronase treatment abolished the ehrlichial antigen present on the cell surface, indicating that this antigen is a protein. Anti-E. risticii serum or immunoglobulin G-mediated antibody-dependent cellular cytotoxicity of infected cells was demonstrated in a chromium release assay. These results imply that the parasite antigen on the host cell surface has a role in the pathogenesis of ehrlichiosis.",,"['Messick, J B', 'Rikihisa, Y']",,,,
,PMC,Human immunodeficiency virus type 1 gag-pol frameshifting is dependent on downstream mRNA secondary structure: demonstration by expression in vivo.,,PMC241392,,,"The human immunodeficiency virus type 1 (HIV-1) Gag-Pol fusion polyprotein is produced via ribosomal frameshifting. Previous studies in vitro and in Saccharomyces cerevisiae have argued against a significant role for RNA secondary structure 3' of the shift site, in contrast with other systems, in which such structure has been shown to be required. Here we show, by expressing the HIV-1 gag-pol domain in cultured vertebrate cells, that a stem-loop structure 3' of the HIV-1 shift site is indeed important for wild-type levels of frameshifting in vivo.",,"['Parkin, N T', 'Chamorro, M', 'Varmus, H E']",,,,
,PMC,Bipartite signal for read-through suppression in murine leukemia virus mRNA: an eight-nucleotide purine-rich sequence immediately downstream of the gag termination codon followed by an RNA pseudoknot.,,PMC241386,,,"The pol gene of murine leukemia virus and other mammalian type C retroviruses is expressed by read-through suppression of an in-frame UAG codon which separates the gag and pol coding regions. In this study, we have analyzed the sequence requirements for read-through suppression by placing different portions of wild-type and mutant viral sequences from the gag-pol junction between reporter genes and testing transcripts of these constructs for suppression in reticulocyte lysates. We find that the read-through signal is contained within the first 57 nucleotides on the 3' side of the UAG codon. Our results indicate that the identities of six conserved bases in the eight-nucleotide, purine-rich sequence immediately downstream of the UAG codon are critical for suppression, as is the existence of a pseudoknot structure spanning the next 49 nucleotides. Thus, read-through suppression depends on a complex, bipartite signal in the mRNA.",,"['Feng, Y X', 'Yuan, H', 'Rein, A', 'Levin, J G']",,,,
,PMC,Herpes simplex virus type 1 entry through a cascade of virus-cell interactions requires different roles of gD and gH in penetration.,,PMC241354,,,"We examined the entry process of herpes simplex virus type 1 (HSV-1) by using infectious virus and previously characterized noninfectious viruses that can bind to cells but cannot penetrate as a result of inactivation of essential viral glycoprotein D (gD) or H (gH). After contact of infectious virus with the cell plasma membrane, discernible changes of the envelope and tegument could be seen by electron microscopy. Noninfectious virions were arrested at distinct steps in interactions with cells. Viruses inactivated by anti-gD neutralizing antibodies attached to cells but were arrested prior to initiation of a visible fusion bridge between the virus and cell. As judged from its increased sensitivity to elution, virus lacking gD was less stably bound to cells than was virus containing gD. Moreover, soluble gD could substantially reduce virus attachment when added to cells prior to or with the addition of virus. Virus inactivated by anti-gH neutralizing antibodies attached and could form a fusion bridge but did not show expansion of the fusion bridge or extensive rearrangement of the envelope and tegument. We propose a model for infectious entry of HSV-1 by a series of interactions between the virion envelope and the cell plasma membrane that trigger virion disassembly, membrane fusion, and capsid penetration. In this entry process, gD mediates a stable attachment that is likely required for penetration, and gH seems to participate in fusion initiation or expansion.",,"['Fuller, A O', 'Lee, W C']",,,,
,PMC,A novel glycoprotein of feline infectious peritonitis coronavirus contains a KDEL-like endoplasmic reticulum retention signal.,,PMC241341,,,"A new protein of feline infectious peritonitis coronavirus (FIPV) was discovered in lysates of [35S]cysteine-labeled infected cells. Expression of open reading frame (ORF) 6b of FIPV in recombinant vaccinia virus-infected cells was used to identify it as the 6b protein. Further characterization revealed that it is a novel type of viral glycoprotein whose function is not clear. It is a soluble protein contained in microsomes; its slow export from the cell is caused by the presence of an endoplasmic reticulum (ER) retention signal at the C terminus. This amino acid sequence, KTEL, closely resembles the consensus KDEL signal of soluble resident ER proteins. A mutant 6b protein with the C-terminal sequence KTEV became resistant to digestion by endo-beta-N-acetylglucosaminidase H with a half-time that was reduced threefold. In contrast, a mutant with the sequence KDEL was completely retained in the ER. The FIPV 6b protein is the first example of a viral protein with a functional KDEL-like ER retention signal.",,"['Vennema, H', 'Heijnen, L', 'Rottier, P J', 'Horzinek, M C', 'Spaan, W J']",,,,
,PMC,The human fibroblast receptor for gp86 of human cytomegalovirus is a phosphorylated glycoprotein.,,PMC241311,,,"A human embryonic lung (HEL) cell receptor for gp86 of human cytomegalovirus that functions in virus-cell fusion was further characterized. Anti-idiotype antibodies that mimic gp86 were used to immunoprecipitate the 92.5-kDa fibroblast membrane receptor for gp86, which was preincubated with various endoglycosidases. The receptor, which has a pI ranging from 5.3 to 5.6, appears to be a glycoprotein with primarily N-linked sugar residues, some of which have high concentrations of mannose and some of which are complex oligosaccharides. Western blots (immunoblots) of electrophoretically transferred receptor incubated with various biotinylated lectins confirmed the presence of sugar moieties, including N-acetylglucosamine, glucose or mannose, and galactose, but not fucose or N-acetylgalactosamine. This gp86 receptor from uninfected HEL cells also incorporated radiolabeled phosphate from orthophosphoric acid, indicating that it is a constitutively phosphorylated receptor.",,"['Keay, S', 'Baldwin, B']",,,,
,PMC,Mutations in the leucine zipper of the human immunodeficiency virus type 1 transmembrane glycoprotein affect fusion and infectivity.,,PMC241301,,,"Many retroviruses, including the human and simian immunodeficiency viruses, contain a leucine zipper-like repeat in a highly conserved region of the external domain of the transmembrane (TM) glycoprotein. This region has been postulated to play a role in stabilizing the oligomeric form of these molecules. To determine what role this region might play in envelope structure and function, several mutations were engineered into the middle isoleucine of the leucine zipper-like repeat of the human immunodeficiency virus type 1 (HIV-1) TM protein. A phenotypic analysis of these mutants demonstrated that conservative mutations (Ile to Val or Leu) did not block the ability of the viral glycoprotein to mediate cell-cell fusion or affect virus infectivity. In contrast, each of the other mutations, except for the Ile-to-Ala change, completely inhibited the ability of the glycoprotein to fuse HeLa-T4 cells and of mutant virions to infect H9 cells. The alanine mutation produced an intermediate phenotype in which both cell fusion and infectivity were significantly reduced. Thus, the biological activity of the glycoprotein titrates with the hydrophobicity of the residue in this position. None of the mutations affected the synthesis, oligomer formation, transport, or processing of the HIV glycoprotein complex. Although these results do not rule out a role for the leucine zipper region in glycoprotein oligomerization, they clearly point to a critical role for it in a post-CD4 binding step in HIV membrane fusion and virus entry.",,"['Dubay, J W', 'Roberts, S J', 'Brody, B', 'Hunter, E']",,,,
,PMC,Coronavirus mRNA transcription: UV light transcriptional mapping studies suggest an early requirement for a genomic-length template.,,PMC241291,,,"Mouse hepatitis virus (MHV) synthesizes seven to eight mRNAs, each of which contains a leader RNA derived from the 5' end of the genome. To understand the mechanism of synthesis of these mRNAs, we studied how the synthesis of each mRNA was affected by UV irradiation at different time points after infection. When MHV-infected cells were UV irradiated at a late time in infection (5 h postinfection), the syntheses of the various mRNAs were inhibited to different extents in proportion to the sizes of the mRNAs. Analysis of the UV inactivation kinetics revealed that the UV target size of each mRNA was equivalent to its own physical size. In contrast, when cells were irradiated at 2.5 or 3 h postinfection, there appeared to be two different kinetics of inhibition of mRNA synthesis: the synthesis of every mRNA was inhibited to the same extent by a small UV dose, but the remaining mRNA synthesis was inhibited by additional UV doses at different rates for different mRNAs in proportion to RNA size. The analysis of the UV inactivation kinetics indicated that the UV target sizes for the majority of mRNAs were equivalent to that of the genomic-size RNA early in the infection. These results suggest that MHV mRNA synthesis requires the presence of a genomic-length RNA template at least early in the infection. In contrast, later in the infection, the sizes of the templates used for mRNA synthesis were equivalent to the physical sizes of each mRNA. The possibility that the genomic-length RNA required early in the infection was used only for the synthesis of a polymerase rather than as a template for mRNA synthesis was ruled out by examining the UV sensitivity of a defective interfering (DI) RNA. We found that the UV target size for the DI RNA early in infection was much smaller than that for mRNAs 6 and 7, which are approximately equal to or smaller in size than the DI RNA. This result indicates that even though DI RNA and viral mRNAs are synthesized by the same polymerase, mRNAs are synthesized from a larger (genomic-length) template. We conclude that a genomic-length RNA template is required for MHV subgenomic mRNA synthesis at least early in infection. Several transcription models are proposed.",,"['Yokomori, K', 'Banner, L R', 'Lai, M M']",,,,
,PMC,New nucleotide sequence data on the EMBL File Server.,,PMC312530,,,,,,,,,
,PMC,Homologous RNA recombination allows efficient introduction of site-specific mutations into the genome of coronavirus MHV-A59 via synthetic co-replicating RNAs.,,PMC312492,,,"We describe a novel strategy to site-specifically mutagenize the genome of an RNA virus by exploiting homologous RNA recombination between synthetic defective interfering (DI) RNA and the viral RNA. The construction of a full-length cDNA clone, pMIDI, of a DI RNA of coronavirus MHV strain A59 was reported previously (R.G. Van der Most, P.J. Bredenbeek, and W.J.M. Spaan (1991). J. Virol. 65, 3219-3226). RNA transcribed from this construct, is replicated efficiently in MHV-infected cells. Marker mutations introduced in MIDI RNA were replaced by the wild-type residues during replication. More importantly, however, these genetic markers were introduced into viral genome: even in the absence of positive selection MHV recombinants could be isolated. This finding provides new prospects for the study of coronavirus replication using recombinant DNA techniques. As a first application, we describe the rescue of the temperature sensitive mutant MHV Albany-4 using DI-directed mutagenesis. Possibilities and limitations of this strategy are discussed.",,"['van der Most, R G', 'Heijnen, L', 'Spaan, W J', 'de Groot, R J']",,,,
,PMC,Development of a biotin-streptavidin-enhanced enzyme-linked immunosorbent assay which uses monoclonal antibodies for detection of group C rotaviruses.,,PMC265361,,,"A biotin-streptavidin-enhanced enzyme-linked immunosorbent assay (ELISA) which uses monoclonal antibodies (MAbs) for the detection of group C rotaviruses was developed. An assay in which plates were coated with three pooled MAbs and biotinylated polyclonal immunoglobulin G (IgG) (polyclonal antibody [PAb]) was used as the detector (MAb capture-PAb detector) was found to be the most sensitive and specific of the assays when it was compared with assays in which plates were coated with polyclonal antiserum and detection was done with either biotinylated polyclonal antiserum (PAb capture-PAb detector) or biotinylated pooled MAbs (PAb capture-MAb detector). The MAb capture-PAb detector ELISA detected 83% of samples confirmed to be positive for group C rotaviruses, whereas the PAb capture-PAb detector assay detected 63% of positive samples and the PAb capture-MAb detector assay detected 65% of positive samples. All three procedures detected both of the bovine and the two human group C rotaviruses, but none of the three procedures detected fecal samples containing group A and B rotaviruses or fecal samples negative for group C rotaviruses used in this study. The sensitivity of the MAb capture-PAb detector ELISA was determined by serially diluting fecal group C rotaviruses; antigens were detected in maximal positive dilution ranges of 1:1,000 to 1:3,000 for the samples tested. On the basis of the cell culture immunofluorescence assay infectivity titer of semipurified cell culture-passaged Cowden group C rotavirus, the sensitivity of the MAb capture-PAb detection ELISA for detection of homologous group C rotavirus was 53 fluorescent focus units per ml. Epitope mapping by use of the biotinylated MAbs in competition assay suggested that our MAbs may bind to three different but overlapping epitopes. These results suggest that the MAb capture-PAb detector ELISA can be used to study the epidemiology of group C rotaviruses in humans and animals.",,"['Ojeh, C K', 'Tsunemitsu, H', 'Simkins, R A', 'Saif, L J']",,,,
,PMC,Localization to the Golgi complex of Uukuniemi virus glycoproteins G1 and G2 expressed from cloned cDNAs.,,PMC241262,,,"The membrane glycoproteins G1 and G2 of Uukuniemi virus, a bunyavirus, accumulate in the Golgi complex (GC) during virus infection. These proteins have therefore been considered to be good models for studying the intracellular transport to and retention in the GC. In this study, I have used indirect immunofluorescence to localize in COS cells the Uukuniemi virus glycoproteins G1 and G2 expressed together or separately from cloned cDNAs with use of simian virus 40-based vectors. When expressed together from the full-length cDNA, G1 and G2 were correctly translocated, processed, and targeted to the GC, indicating that the information for GC targeting resides in the proteins. When the proteins were expressed separately, G1 was transported to the GC and retained there. In contrast, G2 could not be detected in the GC but was most probably retained and finally degraded in the endoplasmic reticulum. However, in cells cotransfected with G1 and G2 cDNAs, the proteins could both again be found in the GC. These results suggest that G1 is a responsible for targeting to and retention of the Uukuniemi virus glycoproteins in the GC. G2 would thus accumulate in the GC by virtue of its binding to G1.",,"Rönnholm, R",,,,
,PMC,Binding of the coronavirus mouse hepatitis virus A59 to its receptor expressed from a recombinant vaccinia virus depends on posttranslational processing of the receptor glycoprotein.,,PMC241205,,,"Recently, we showed that a murine member of the carcinoembryonic antigen family of glycoproteins serves as a cellular receptor (MHVR) for the coronavirus mouse hepatitis virus A59 (MHV-A59) (G. S. Dveksler, M. N. Pensiero, C. B. Cardellichio, R. K. Williams, G.-S. Jiang, K. V. Holmes, and C. W. Dieffenbach, J. Virol. 65:6881-6891, 1991; R. K. Williams, G.-S. Jiang, and K. V. Holmes, Proc. Natl. Acad. Sci. USA 88:5533-5536, 1991). To examine the role of posttranscriptional modification of MHVR on virus-receptor interactions, a vaccinia virus-based expression system was employed. Expression from the vaccinia virus recombinant (Vac-MHVR) in BHK-21 cells resulted in high levels of MHVR glycoprotein on the cell surface and made these cells susceptible to MHV-A59 infection. Nonglycosylated core MHVR proteins were made in Vac-MHVR-infected BHK-21 cells in the presence of tunicamycin by in vitro translation of MHVR mRNA in a rabbit reticulocyte cell-free system in the absence of microsomal membranes and by expression of an N-terminal deletion clone of MHVR lacking its signal peptide. These three nonglycosylated MHVR proteins were recognized by polyclonal antibody against affinity-purified receptor but did not bind antireceptor monoclonal antibody (MAb) CC1 or MHV-A59 virions. Partial glycosylation of MHVR, either expressed in Vac-MHVR-infected cells treated with monensin or synthesized by in vitro translation with microsomal membranes, restored both the MAb CC1- and the virus-binding activities of the MHVR glycoprotein. Deletion of 26 amino acids at the carboxyl terminus of MHVR resulted in a secreted protein which was able to bind MAb CC1 and MHV-A59. These results suggest that either a carbohydrate moiety is an element of the MHVR-binding site(s) for virus and MAb CC1 or a posttranslational membrane-associated process is required for functional conformation of the receptor glycoprotein.",,"['Pensiero, M N', 'Dveksler, G S', 'Cardellichio, C B', 'Jiang, G S', 'Elia, P E', 'Dieffenbach, C W', 'Holmes, K V']",,,,
,PMC,New nucleotide sequence data on the EMBL File Server.,,PMC312473,,,,,,,,,
,PMC,"Arthritis induced in rats with adjuvant oil is a genetically restricted, alpha beta T-cell dependent autoimmune disease.",,PMC1421552,,,"Adjuvant arthritis in rats is usually induced by injection of mycobacterium tubercle cell walls suspended in various adjuvant oils such as Freund's incomplete adjuvant (FIA) or pristane. We have recently shown that injection of adjuvant oils without inclusion of mycobacterium tubercle cell walls triggers arthritis [oil adjuvant-induced arthritis (OIA)] in the DA rat strain. The OIA is a genetically restricted disease since only DA rats are susceptible while Lewis, DA-fostered Lewis and F1 (Lew x DA) rats are relatively resistant. Activated alpha beta T cells infiltrate the affected joints of adjuvant oil-injected DA rats and treatment with monoclonal antibodies to the alpha beta T-cell receptor abrogates development of arthritis. These findings show that alpha beta T-cell activation is a critical event in the development of OIA.",,"['Holmdahl, R', 'Goldschmidt, T J', 'Kleinau, S', 'Kvick, C', 'Jonsson, R']",,,,
,PMC,Evaluation of an enzyme immunoassay kit for detecting cryptosporidium in faeces and environmental samples.,,PMC495218,,,"AIMS: To evaluate a commercially available enzyme immunoassay based on a monoclonal antibody to a genus specific Cryptosporidium (IDEIA Cryptosporidium; Dako) antigen for detecting Cryptosporidium oocysts in faecal and environmental samples. METHODS: 435 human faecal samples and post-filtration deposits from 10 reservoir samples, and from six tap water samples seeded with Cryptosporidium oocysts, were examined by EIA according to the manufacturer's instructions, and by microscopic examination of phenolauramine stained smears. Samples giving discrepant results were examined by specific immunofluorescence, before and after concentration of oocysts. RESULTS: Sixteen (3.6%) faecal samples were positive by both microscopy and EIA; five (1.1%) were positive by microscopy of auramine-phenol stained smears (but were not confirmed by specific immunofluorescence) and negative by EIA; one (0.2%) was positive by EIA alone, but confirmed by specific immunofluorescence; and 362 (83.2%) were negative by both microscopy and EIA. Compared with immunofluorescence positive faecal samples, the sensitivity of conventional microscopy and EIA were 94% and 100%, and specificity 76.4% and 100%, respectively. Fifty one (11.7%) were not examined by microscopy due to detection of other pathogens in a previous sample from that patient, but were found to be negative by EIA. Ten reservoir water samples (not suspected of being linked to cases of cryptosporidiosis) were negative by both microscopy and EIA. Of six samples of tap water seeded with varying concentrations of Cryptosporidium oocysts, two (10(2) and 10(3) oocysts/l) were positive by both microscopy and EIA, two (10 and 1/l) by EIA alone, and two (0.1/l and unseeded water) were negative by both microscopy and EIA. CONCLUSIONS: The kit is simple and rapid to use and offers a less subjective method than microscopy for detecting Cryptosporidium in faecal samples submitted to a busy diagnostic laboratory.",,"['Siddons, C. A.', 'Chapman, P. A.', 'Rush, B. A.']",,,,
,PMC,Ribosomal frameshifting efficiency and gag/gag-pol ratio are critical for yeast M1 double-stranded RNA virus propagation.,,PMC241150,,,"About 1.9% of ribosomes translating the gag open reading frame of the yeast L-A double-stranded RNA virus positive strand undergo a -1 frameshift and continue translating in the pol open reading frame to make a 170-kDa gag-pol fusion protein. The importance of frameshifting efficiency for viral propagation was tested in a system where the M1 (killer toxin-encoding) satellite RNA is supported by a full-length L-A cDNA clone. Either increasing or decreasing the frameshift efficiency more than twofold by alterations in the slippery site disrupted viral propagation. A threefold increase caused by a chromosomal mutation, hsh1 (high shifter), had the same effect. Substituting a +1 ribosomal frameshift site from Ty1 with the correct efficiency also allowed support of M1 propagation. The normal -1 frameshift efficiency is similar to the observed molar ratio in viral particles of the 170-kDa gag-pol protein to the 70-kDa gag gene product, the major coat protein. The results are interpreted in terms of a packaging model for L-A.",,"['Dinman, J D', 'Wickner, R B']",,,,
,PMC,Identification and characterization of a coronavirus packaging signal.,,PMC241133,,,"Previously, a mouse hepatitis virus (MHV) genomic sequence necessary for defective interfering (DI) RNA packaging into MHV particles (packaging signal) was mapped to within a region of 1,480 nucleotides in the MHV polymerase gene by comparison of two DI RNAs. One of these, DIssF, is 3.6 kb in size and exhibits efficient packaging, whereas the other, DIssE, which is 2.3 kb, does not. For more precise mapping, a series of mutant DIssF RNAs with deletions within this 1,480-nucleotide region were constructed. After transfection of in vitro-synthesized mutant DI RNA in MHV-infected cells, the virus product was passaged several times. The efficiency of DI RNA packaging into MHV virions was then estimated by viral homologous interference activity and by analysis of intracellular virus-specific RNAs and virion RNA. The results indicated that an area of 190 nucleotides was necessary for packaging. A computer-generated secondary structural analysis of the A59 and JHM strains of MHV demonstrated that within this 190-nucleotide region a stable stem-loop of 69 nucleotides was common between the two viruses. A DIssE-derived DI DNA which had these 69 nucleotides inserted into the DIssE sequence demonstrated efficient DI RNA packaging. Site-directed mutagenic analysis showed that of these 69 nucleotides, the minimum sequence of the packaging signal was 61 nucleotides and that destruction of the secondary structure abolished packaging ability. These studies demonstrated that an MHV packaging signal was present within the 61 nucleotides, which are located on MHV genomic RNA 1,381 to 1,441 nucleotides upstream of the 3' end of gene 1.",,"['Fosmire, J A', 'Hwang, K', 'Makino, S']",,,,
,PMC,Mechanism of coronavirus transcription: duration of primary transcription initiation activity and effects of subgenomic RNA transcription on RNA replication.,,PMC241112,,,"Previously, we established a system whereby an intergenic region from mouse hepatitis virus (MHV) inserted into an MHV defective interfering (DI) RNA led to transcription of a subgenomic DI RNA in helper virus-infected cells. By using this system, the duration of a primary transcription initiation activity which transcribes subgenomic-size RNAs from the genomic-size RNA template in MHV-infected cells was examined. Efficient DI genomic and subgenomic RNA synthesis was observed when the DI RNA was transfected at 1, 3, 3.5, 5, and 6 h postinfection, indicating that all activities which are necessary for MHV RNA synthesis are present continuously during the first 6 h of infection. The effect of subgenomic DI RNA synthesis on DI genomic RNA replication was then examined. Replication efficiency of the DI genomic RNA which synthesized the subgenomic RNA was approximately 70% lower than that of DI genomic RNA which did not synthesize the subgenomic DI RNA in MHV-infected cells. Cotransfection of two different-size DI RNAs demonstrated that replication of the larger DI RNA was strongly inhibited by replication of the smaller genomic DI RNA. Cotransfection of two DI RNA species of the same length into MHV-infected cells demonstrated that reduced replication of the genomic DI RNA which synthesizes the subgenomic RNA did not affect the replication of cotransfected DI RNA, demonstrating that the reduction in DI genomic RNA replication works only in cis, not in trans. Therefore, the previously proposed hypothesis that coronavirus, subgenomic RNA synthesis may inhibit the replication of genomic RNA by competing for a limited amount of virus-derived factors seems unlikely. Possible mechanisms of coronavirus transcription are discussed.",,"['Jeong, Y S', 'Makino, S']",,,,
,PMC,"Golgi retention of a trans-Golgi membrane protein, galactosyltransferase, requires cysteine and histidine residues within the membrane-anchoring domain.",,PMC49073,,,"Galactosyltransferase (GT; UDPgalactose:beta-D-N-acetylglucosaminide beta-1,4-galactosyltransferase, EC 2.4.1.22) is a type II membrane-anchored protein composed of a short N-terminal cytoplasmic tail, a signal/membrane-anchoring domain, and a stem region followed by a large catalytic domain including the C terminus. To identify the peptide segment and key amino acid residues that are critical for Golgi localization of GT, the expression vector pGT-hCG was designed to encode the entire GT molecule fused to the C-terminal region of human chorionic gonadotropin alpha subunit (hCG alpha) as a reporter. COS-1 cells transfected with pGT-hCG expressed the chimera in the Golgi region, as detected by immunofluorescence microscopy using anti-hCG antibodies. Two deletion mutants, delta tail and delta stem, which are lacking most of the N-terminal cytoplasmic tail or 10 amino acids immediately after the membrane-anchoring domain, were localized in the Golgi. Replacement mutations of the membrane-anchoring domain of GT showed that the second quarter of the transmembrane domain or Cys29-Ala30-Leu31-His32-Leu33 is necessary for GT to be retained in the Golgi. Furthermore, the point mutants Cys29----Ser29 and His32----Leu32 were partially transported to the plasma membrane, whereas an Ala30-Leu31----Phe30-Gly31 mutant was localized in the Golgi. Finally, a double mutant, Cys29/His32----Ser29/Leu32, was found to be transported efficiently to the plasma membrane. The signal-anchoring domain of the transferrin receptor, a type II plasma membrane protein, was then replaced by portions of the GT transmembrane domain. Although the Cys-Xaa-Xaa-His sequence by itself cannot retain the transferrin receptor in the Golgi, the cytoplasmic half of the transmembrane domain of GT was partially capable of retaining the transferrin receptor in the Golgi. These results suggest that the cytoplasmic (or N-terminal) half of the transmembrane domain of GT contributes to the Golgi retention signal and that particularly Cys29 and His32 in this region are critical for GT to be retained in the Golgi.",,"['Aoki, D', 'Lee, N', 'Yamaguchi, N', 'Dubois, C', 'Fukuda, M N']",,,,
,PMC,Susceptibility to Theiler's virus-induced demyelinating disease correlates with astrocyte class II induction and antigen presentation.,,PMC1421736,,,"Theiler's murine encephalomyelitis virus (TMEV) is a picornavirus which induces a chronic demyelinating disease of the central nervous system (CNS) in certain susceptible mouse strains. Demyelination has been shown to result from immunopathological responses mediated by CD4+, major histocompatibility complex (MHC) class II-restricted T cells. As little or no class II is expressed in the normal mouse CNS, the ability of astrocytes to express these proteins and present antigen to T cells from TMEV-infected mice was investigated here. It is shown that astrocytes are capable of presenting TMEV to virus-specific T cells in vitro, and that this ability is dependent on prior induction of MHC class II by interferon-gamma (IFN-gamma) treatment. Unlike other viruses such as murine hepatitis virus-JHM (a coronavirus) and measles, TMEV is not capable of inducing class II on astrocytes directly. There is a correlation between the ease of class II induction on astrocytes from different mouse strains by IFN-gamma and mouse strain susceptibility to TMEV-induced demyelinating disease. These results suggest that following viral infection and initial T-cell infiltration into the CNS, class II induction on astrocytes is a key step allowing local antigen presentation and amplification of immunopathological responses within the CNS and hence the development of demyelinating disease.",,"['Borrow, P', 'Nash, A A']",,,,
,PMC,The full-length transcript of a caulimovirus is a polycistronic mRNA whose genes are trans activated by the product of gene VI.,,PMC241076,,,"Gene expression of figwort mosaic virus (FMV), a caulimovirus, was investigated by electroporation of Nicotiana edwardsonii cell suspension protoplasts with cloned viral constructs in which a reporter gene was inserted at various positions on the genome. The results showed that the genome of FMV contains two promoters; one is used for the production of a full-length RNA and another initiates synthesis of a separate monocistronic RNA for gene VI. Evidence is provided that the full-length transcript, the probable template for reverse transcription, can serve as a polycistronic mRNA for translation of genes I through V and perhaps also gene VI. Expression of all the genes on the polycistronic mRNA is trans activated by the gene VI protein. Reporter gene expression appears most efficient when its start codon is in close proximity to the stop codon of the preceding gene, as for the native genes of caulimoviruses. We propose that the gene VI product enables expression of the polycistronic mRNA by promoting reinitiation of ribosomes to give translational coupling of individual genes.",,"['Scholthof, H B', 'Gowda, S', 'Wu, F C', 'Shepherd, R J']",,,,
,PMC,Coding capacity determines in vivo accumulation of a defective RNA of clover yellow mosaic virus.,,PMC241068,,,"Naturally occurring defective RNAs (D RNAs) derived from the potexvirus clover yellow mosaic virus (CYMV) contain large internal deletions yet maintain a single open reading frame (ORF) representing the in-frame fusion of 5' and 3' terminal ORFs. Capped transcripts of the prototype 1.2-kb D RNA of CYMV were synthesized in vitro and used to inoculate broad bean plants. Progeny D RNA accumulated only if synthetic D RNA transcripts were coinoculated with CYMV RNA. Several experiments showed that helper-dependent accumulation of the D RNA in vivo depended on the maintenance of its encoded fusion ORF. (i) D RNAs with six-residue deletions introduced early in the fusion ORF accumulated, whereas those with four-residue out-of-frame deletions at the same sites were nonviable. (ii) Analysis of D RNAs containing termination codons at different locations showed that only the most 3' stop codon (maintaining over 93% of the fusion ORF) was permissive for D RNA accumulation. (iii) D RNAs with small in-frame deletions and insertions in their 3' coding regions were viable. (iv) Nonviable D RNAs containing disrupted fusion ORFs could not be complemented by the presence in the infection of a D RNA encoding a complete fusion ORF. Taken together, the results indicate that the process of translation, rather than the encoded product, modulates an event(s) which influences the propagation and/or accumulation of this RNA in vivo. This represents a unique requirement among plant virus D RNAs.",,"['White, K A', 'Bancroft, J B', 'Mackie, G A']",,,,
,PMC,Hemagglutinin-esterase-specific monoclonal antibodies alter the neuropathogenicity of mouse hepatitis virus.,,PMC241045,,,"Some of mouse hepatitis virus strains contain an optional envelope glycoprotein, hemagglutinin-esterase (HE) protein. To understand the functional significance of this protein, monoclonal antibodies (MAbs) specific for this protein were generated and used for passive immunization of mice. None of these MAbs showed any virus-neutralizing activity in vitro; however, mice passively immunized with the purified MAbs were protected from lethal infection by the JHM strain of mouse hepatitis virus. Passive immunization altered the pathogenicity such that the virus caused subacute and chronic demyelination instead of acute lethal encephalitis. Virus titers in the brains of the immunized mice were significantly lower than those for the nonimmunized control mice, suggesting that the virus replication or spread was inhibited. In addition, histopathological analysis indicated that the spread of virus in the brain and spinal cord was significantly inhibited in the immunized mice. Furthermore, the mononuclear cell infiltration in the immunized mice appeared earlier than in the nonimmunized mice, suggesting that the exogenous antibody might have activated host immune responses, and thus facilitated clearance of the virus or virus-infected cells. The same protective effects were observed for both JHM(2) and JHM(3) viruses, which expressed different amounts of the HE protein. In contrast, mice infected with At11f, a variant of JHM which does not express the HE protein, were not protected by these MAbs, suggesting that protection was mediated by the specific interaction between the MAb and the HE protein. Thus, the mechanism of protection by the exogenous HE-specific MAbs may represent the early activation of innate immune mechanisms in response to the interaction between the MAbs and the HE protein.",,"['Yokomori, K', 'Baker, S C', 'Stohlman, S A', 'Lai, M M']",,,,
,PMC,Duck hepatitis B virus infection of hepatocytes is not dependent on low pH.,,PMC241040,,,"The pH dependency for initiation of infection by the hepadnavirus duck hepatitis B virus (DHBV) was investigated in primary duck hepatocytes. First, an infection assay was developed using a radioimmunoblot to measure DHBV e antigen secreted into tissue culture fluid from infected hepatocytes. The quantity of this viral marker was proportional to the duration of inoculation and the amount of DHBV used as inoculum. The role of pH in initiation of DHBV infection was investigated by using this assay, but no dependence on low pH was found. DHBV was able to infect hepatocytes in the presence of NH4Cl and monensin, agents that raise the pH in intracellular vesicles and prevent penetration of viruses dependent on low pH in endosomes. In control experiments, infection by Semliki Forest virus, which is low pH dependent, was inhibited, whereas herpes simplex virus type 1 infection, which is pH independent, occurred. Attempts to trigger DHBV-cell fusion by exposure of DHBV prebound to hepatocytes to mildly acidic pH were unsuccessful. In these experiments, it was also observed that internalization of DHBV occurred only between pH 6.8 and 8.0. Additionally, in the absence of cells, infectivity of DHBV was stable at pH 4.6 to 4.8, which is lower than the pH encountered in endosomes (pH 5 to 6.6). Thus, no evidence for a role for mildly acidic pH in the initiation of DHBV infection was found. Therefore, we propose that the infection route followed by DHBV resembles that of the group of enveloped viruses, including herpesviruses, that fuse with their host cells at neutral pH.",,"['Rigg, R J', 'Schaller, H']",,,,
,PMC,New nucleotide sequence data on the EMBL File Server.,,PMC312288,,,,,,,,,
,PMC,Transmissible gastroenteritis virus antibody production in vitro by porcine peripheral blood leukocytes.,,PMC1263529,,,"The purpose of this study was to demonstrate the in vitro production of transmissible gastroenteritis virus (TGEV)-specific antibodies by peripheral blood leukocytes (PBL) harvested from piglets infected with TGEV. Piglets were infected with the virulent Purdue strain of TGEV and at intervals postinfection their PBL were cultivated in the presence of TGEV antigen, control antigen or pokeweed mitogen (PWM). The culture supernatants were tested for TGEV antibodies by a fixed cell enzyme immunoassay. Antibodies were never found in the supernatants of unprimed PBL cultures from control piglets, nor in cultures stimulated with control antigen, and antibodies were produced more frequently in response to stimulation of primed PBL with viral antigen than with PWM. In PBL cultures stimulated with viral antigen, TGEV antibodies of the IgG class were produced more frequently than IgA class antibodies. Optimal antibody responses were produced by PBL harvested two weeks after infection and cultivated at a concentration of 10(7) cells/mL for five days.",,"['Naidoo, D', 'Derbyshire, J B']",,,,
,PMC,Efficacy of antiserum produced in goats and pigs to passively protect piglets against virulent transmissible gastroenteritis virus.,,PMC1263528,,,"The protective effect of sera produced in swine and goats exposed to virulent transmissible gastroenteritis virus (TGEV) or modified-live TGEV was tested in hysterectomy-derived, colostrum-deprived three-day-old pigs. Pigs were given serum with their daily ration of milk, and their immunity to virulent TGEV was determined. The pigs were observed for ten days for clinical signs of TGEV infection. One of nine pigs receiving goat serum was protected whereas all three pigs receiving three doses of swine serum per day were protected. Because virus was not isolated from the goats after oral/intranasal vaccination, it is suggested the virus did not replicate in either the respiratory or digestive tract of the goat.",,"['Woods, R D', 'Wesley, R D']",,,,
,PMC,"Hemorrhagic gastroenteritis caused by Escherichia coli in piglets: Clinical, pathological and microbiological findings",,PMC1481210,,,"A retrospective study (1980-1989) was conducted to describe the clinical, pathological, and bacteriological findings in 55 cases of hemorrhagic gastroenteritis (HGE) caused by Escherichia coli in piglets. The condition occurred in weaned and suckling piglets and was associated with several serogroups of E. coli. Most of the isolates of E. coli possessed the adhesin F4 (K88) and were hemolytic. Only a few of the isolates of E. coli tested produced verotoxins. Clinical signs and pathological findings noted in these cases were compatible with shock.",,"['Faubert, Claude', 'Drolet, Richard']",,,,
,PMC,Vaccination and genetic experiments demonstrate that adjuvant-oil-induced arthritis and homologous type II collagen-induced arthritis in the same rat strain are different diseases.,,PMC1554355,,,"The DA rat is highly susceptible to induction of arthritis after immunization with homologous type II collagen (CII) emulsified in Freund's incomplete adjuvant (FIA), resulting in collagen-induced arthritis (CIA). The DA rat also develops arthritis after injection of FIA alone (oil-induced arthritis (OIA)). This finding allows a direct comparison of two different models for rheumatoid arthritis; one induced with a defined auto-immunogen and one with a pure adjuvant. Both CIA and OIA develop approximately 2 weeks after induction but OIA is a self-limited acute disease whereas CIA induced with homologous CII follows a chronic disease course. Immunization with CII leads to a strong autoantibody response to CII while injection of FIA leads to no or very limited anti-CII antibody response. The Lewis rat develops neither CIA nor OIA while F1 (DA x Lewis) rats develop CIA but not OIA. Olive oil or CII emulsified in olive oil does not induce arthritis in DA rats. Pretreatment with CII in olive oil vaccinates against CIA but not OIA whereas pretreatment with FIA vaccinates against OIA but not CIA. These findings demonstrate that inclusion of CII in the adjuvant leads to a disease distinct from OIA which is characterized by a CII autoimmune response and chronicity of the disease course.",,"['Holmdahl, R', 'Kvick, C']",,,,
,PMC,IgG subclass responses to Theiler's murine encephalomyelitis virus infection and immunization suggest a dominant role for Th1 cells in susceptible mouse strains.,,PMC1384845,,,"Inbred mouse strains differ in susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. A strong correlation between disease susceptibility and delayed-type hypersensitivity (DTH) has been previously demonstrated, but no strong correlation between disease susceptibility and total anti-TMEV ELISA titres was shown. Since both DTH and IgG2a antibody production are regulated by CD4+ Th1 cells, we investigated three strains of mice to determine whether antivirus IgG2a antibody levels, like DTH in previous studies, correlated with disease susceptibility. Susceptible SJL/J, intermediately susceptible C3H/HeJ, and resistant C57BL/6 mice were infected intracerebrally (i.c.) with the BeAn strain of TMEV and monitored for clinical signs of demyelination and for levels of TMEV-specific antibody of different IgG subclasses using a particle concentration fluorescence immunoassay (PCFIA). Resistant C57BL/6 mice were found to have significantly lower concentrations of total anti-TMEV antibody than susceptible SJL/J mice and intermediately susceptible C3H/HeJ mice show variable antibody responses. A predominance of anti-TMEV IgG2a (Th1 regulated) antibody was seen in susceptible and intermediately susceptible mice, whereas resistant mice displayed a predominant anti-TMEV IgG1 (Th2 regulated) response accompanied by a marked deficiency of IgG2a. In contrast, immunization of C57BL/6 mice with UV-inactivated TMEV in adjuvant revealed that this strain was not defective either in its ability to generate high levels of anti-TMEV antibody or in its ability to produce IgG2a antibody. These results suggest that the antivirus IgG subclass profile is dependent upon the immunization route, virus viability and/or the use of adjuvant and that the levels of antivirus subclasses may be predictive of disease susceptibility.",,"['Peterson, J D', 'Waltenbaugh, C', 'Miller, S D']",,,,
,PMC,Reversion of Q beta RNA phage mutants by homologous RNA recombination.,,PMC289039,,,"Q beta phage RNAs with inactivating insertion (8-base) or deletion (17-base) mutations within their replicase genes were prepared from modified Q beta cDNAs and transfected into Escherichia coli spheroplasts containing Q beta replicase provided in trans by a resident plasmid. Replicase-defective (Rep-) Q beta phage produced by these spheroplasts were detected as normal-sized plaques on lawns of cells containing plasmid-derived Q beta replicase, but were unable to form plaques on cells lacking this plasmid. When individual Rep- phage were isolated and grown to high titer in cells containing plasmid-derived Q beta replicase, revertant (Rep+) Q beta phage were obtained at a frequency of ca. 10(-8). To investigate the mechanism of this reversion, a point mutation was placed into the plasmid-derived Q beta replicase gene by site-directed mutagenesis. Q beta mutants amplified on cells containing the resultant plasmid also yielded Rep+ revertants. Genomic RNA was isolated from several of the latter phage revertants and sequenced. Results showed that the original mutation (insertion or deletion) was no longer present in the phage revertants but that the marker mutation placed into the plasmid was now present in the genomic RNAs, indicating that recombination was one mechanism involved in the reversion of the Q beta mutants. Further experiments demonstrated that the 3' noncoding region of the plasmid-derived replicase gene was necessary for the reversion-recombination of the deletion mutant, whereas this region was not required for reversion or recombination of the insertion mutant. Results are discussed in terms of a template-switching model of RNA recombination involving Q beta replicase, the mutant phage genome, and plasmid-derived replicase mRNA.",,"['Palasingam, K', 'Shaklee, P N']",,,,
,PMC,Repair and mutagenesis of the genome of a deletion mutant of the coronavirus mouse hepatitis virus by targeted RNA recombination.,,PMC288970,,,"The genetic characterization of a nucleocapsid (N) protein mutant of the coronavirus mouse hepatitis virus (MHV) is described. The mutant, Albany 4 (Alb4), is both temperature sensitive and thermolabile. Analysis of the progeny of a mixed infection showed that the defective Alb4 allele is recessive to wild type, and its gene product is diffusible. The N protein of Alb4 was found to be smaller than its wild-type counterpart, and sequence analysis of the Alb4 N gene revealed that it contains an internal deletion of 87 nucleotides, producing an in-frame deletion of 29 amino acids. All of these properties of Alb4 made it ideal for use as a recipient in a targeted RNA recombination experiment in which the deletion in Alb4 was repaired by recombination with synthetic RNA7, the smallest MHV subgenomic mRNA. Progeny from a cotransfection of Alb4 genomic RNA and synthetic RNA7 were selected for thermal stability. Polymerase chain reaction analysis of candidate recombinants showed that they had regained the material that is deleted in the Alb4 mutant. They also had acquired a five-nucleotide insertion in the 3' untranslated region, which had been incorporated into the synthetic RNA7 as a molecular tag. The presence of the tag was directly verified, as well, by sequencing the genomic RNA of purified recombinant viruses. This provided a clear genetic proof that the Alb4 phenotype was due to the observed deletion in the N gene. In addition, these results demonstrated that it is possible to obtain stable, independently replicating progeny from recombination between coronavirus genomic RNA and a tailored, synthetic RNA species.",,"['Koetzner, C A', 'Parker, M M', 'Ricard, C S', 'Sturman, L S', 'Masters, P S']",,,,
,PMC,Translational frameshifting mediated by a viral sequence in plant cells.,,PMC48637,,,"It has been proposed that the polymerase gene of barley yellow dwarf virus and related viruses is expressed by a ribosomal frameshift event during translation. The 5' end of this gene overlaps with the 3' end of an upstream gene that is in a different reading frame. The region of overlap is similar to sequences in retro- and coronaviruses that are known to express their polymerase genes by frameshifting. This overlap region includes a ""shifty"" heptanucleotide, followed by a highly structured region that may contain a pseudoknot. Sequences of 115 or 144 base pairs that span this region from barley yellow dwarf virus (PAV serotype) genomic RNA were introduced into a plasmid, so that a reporter gene could be expressed in plant cells only if a minus one (-1) frameshift event occurred. Frameshifting was detected at a rate of approximately 1%. This frameshifting was abolished when the stop codon at the 3' end of the upstream open reading frame was deleted. A sequence expected to form a strong stem-loop immediately upstream of the frameshift site was unnecessary for frameshifting, and initiation at AUG codons within the stem-loop appeared to be inhibited. Like viruses that infect hosts in other kingdoms, plant viruses also can induce frameshifting in translation of their genes.",,"['Brault, V', 'Miller, W A']",,,,
,PMC,Ribosomal frameshifting in plants: a novel signal directs the -1 frameshift in the synthesis of the putative viral replicase of potato leafroll luteovirus.,,PMC556553,,,"The 5.8 kb RNA genome of potato leafroll luteovirus (PLRV) contains two overlapping open reading frames, ORF2a and ORF2b, which are characterized by helicase and RNA polymerase motifs, respectively, and possibly represent the viral replicase. Within the overlap, ORF2b lacks an AUG translational start codon and is therefore presumably translated by -1 ribosomal frameshifting as a transframe protein with ORF2a. This hypothesis was studied by introducing the putative frameshift region into an internal position of the beta-glucuronidase (GUS) gene and testing for the occurrence of frameshifting in vivo by transient expression of GUS activity in potato protoplasts as well as in vitro by translation in the reticulocyte system. Both experimental approaches demonstrate that a -1 frameshift occurs at a frequency of approximately 1%. Site-directed mutagenesis identified the frameshift region and the involvement of the novel heptanucleotide motif UUUAAAU in conjunction with an adjacent stem-loop structure. Part of this stem-loop encodes a basic region in the ORF2b moiety of the transframe protein which was shown by binding experiments with PLRV RNA to represent a nucleic acid-binding domain. These data support a possible biological significance of the frameshift to occur at this position of the large overlap by including the putative RNA template-binding site of the PLRV replicase in the ORF2a/ORF2b transframe protein.",,"['Prüfer, D', 'Tacke, E', 'Schmitz, J', 'Kull, B', 'Kaufmann, A', 'Rohde, W']",,,,
,PMC,Mouse hepatitis virus infection suppresses modulation of mouse spleen T-cell activation.,,PMC1384752,,,"Natural infection by mouse hepatitis virus (MHV) can affect interpretation of immunological studies in mice. MHV, a collective term describing a group of corona viruses, is found in natural infections in over 70% of laboratory mouse populations in the U.S.A. and Canada. Natural outbreaks of MHV in our animal colony afforded us the opportunity to study MHV-induced immunosuppression as well as the effects of MHV infection on neurotransmitter immunomodulation. Concanavalin A (Con A)-stimulated DNA synthesis by spleen T lymphocytes from MHV-infected mice was 20-50% that of non-infected mice. The MHV infection also altered neurotransmitter modulation of spleen T-lymphocyte activation. In contrast to noradrenaline ablation of Con A-activated DNA synthesis by spleen lymphocytes from non-infected mice, DNA synthesis by the infected group was not inhibited by noradrenaline or dibutyryl-cAMP. These effects of MHV infection were specific for spleen T lymphocytes since MHV infection did not alter Con A stimulation of thymocytes, lipopolysaccharide stimulation of spleen B lymphocytes, or noradrenaline inhibition of thymocyte and B-cell DNA synthesis. MHV infection also did not alter spleen T-lymphocyte subset proportions. Thus, MHV infection inhibits spleen T-lymphocyte activation and blocks in vitro catecholamine and cAMP regulation of spleen T-cell activation but does not affect activation of thymic cells or spleen B cells.",,"['Cook-Mills, J M', 'Munshi, H G', 'Perlman, R L', 'Chambers, D A']",,,,
,PMC,Monoclonal antibody solution hybridization assay for detection of mouse hepatitis virus infection.,,PMC265119,,,"A monoclonal antibody solution hybridization (MASH) assay was developed to detect fecal excretion of mouse hepatitis virus (MHV). The assay used a biotinylated cDNA probe to detect viral RNA target sequences by hybridization in solution, capture of hybrids on the solid phase with antibiotin antibody, and immunoassay with an enzyme-labelled monoclonal antibody specific for DNA-RNA hybrids. The MASH assay was used to monitor the time course of enterotropic MHV excretion after oronasal inoculation. Infectivity of the inoculated mice was simultaneously monitored with sentinel animals. The MASH assay detected MHV excretion in all inoculated mice, with the highest mean excretion levels occurring from day 3 through day 9 postinoculation. Mean excretion then decreased gradually to below detection limits by day 21 postinoculation. Sentinels became infected on exposure to inoculated mice up to but not after day 21 postinoculation. Infected sentinel mice showed a time course of virus excretion similar to that of inoculated mice. These results indicate that the MASH assay is useful for rapid, sensitive, and specific detection of MHV in clinical specimens from laboratory mice.",,"['Casebolt, D B', 'Stephensen, C B']",,,,
,PMC,RNA recombination in animal and plant viruses.,,PMC372854,,,"An increasing number of animal and plant viruses have been shown to undergo RNA-RNA recombination, which is defined as the exchange of genetic information between nonsegmented RNAs. Only some of these viruses have been shown to undergo recombination in experimental infection of tissue culture, animals, and plants. However, a survey of viral RNA structure and sequences suggests that many RNA viruses were derived form homologous or nonhomologous recombination between viruses or between viruses and cellular genes during natural viral evolution. The high frequency and widespread nature of RNA recombination indicate that this phenomenon plays a more significant role in the biology of RNA viruses than was previously recognized. Three types of RNA recombination are defined: homologous recombination; aberrant homologous recombination, which results in sequence duplication, insertion, or deletion during recombination; and nonhomologous (illegitimate) recombination, which does not involve sequence homology. RNA recombination has been shown to occur by a copy choice mechanism in some viruses. A model for this recombination mechanism is presented.",,"Lai, M M",,,,
,PMC,Cytoplasmic domain of P-selectin (CD62) contains the signal for sorting into the regulated secretory pathway.,,PMC275532,,,"P-selectin (CD62), formerly called GMP-140 or PADGEM, is a membrane protein located in secretory storage granules of platelets and endothelial cells. To study the mechanisms responsible for the targeting of P-selectin to storage granules, we transfected its cDNA into COS-7 and CHO-K1 cells, which lack a regulated exocytic pathway, or into AtT20 cells, which are capable of regulated secretion. P-selectin was expressed on the plasma membrane of COS-7 and CHO-K1 cells but was concentrated in storage granules of AtT20 cells. Immunogold electron microscopy indicated that the electron-dense granules containing P-selectin in AtT20 cells also stored the endogenous soluble hormone ACTH. Activation of AtT20 cells with 8-Br-cAMP increased the surface expression of P-selectin, consistent with agonist-induced fusion of granule membranes with the plasma membrane. Deletion of the last 23 amino acids of the 35-residue cytoplasmic domain resulted in delivery of P-selectin to the plasma membrane of AtT20 cells. Replacement of the cytoplasmic tail of tissue factor, a plasma membrane protein, with the cytoplasmic domain of P-selectin redirected the chimeric molecule to granules. We conclude that the cytoplasmic domain of P-selectin is both necessary and sufficient for sorting of membrane proteins into the regulated pathway of secretion.",,"['Disdier, M', 'Morrissey, J H', 'Fugate, R D', 'Bainton, D F', 'McEver, R P']",,,,
,PMC,New nucleotide sequence data on the EMBL File Server.,,PMC312073,,,,,,,,,
,PMC,Vaccination guidelines for dogs and cats: 1992 update: CVMA Practice Committee,,PMC1481150,,,,,"['Shacklady, Edward', 'Houle, Louise', 'McKenzie, Neil T.', 'Prowse, Ernest', 'Christmas, Richard']",,,,
,PMC,Paralysis of street rabies virus-infected mice is dependent on T lymphocytes.,,PMC240838,,,"Street rabies virus (SRV)-infected T-lymphocyte-deficient (nude) mice, in contrast to euthymic mice, did not develop hindlimb paralysis prior to death. To document the role of T lymphocytes in rabies virus-associated paralysis, 10(8) spleen cells from normal immunocompetent euthymic mice were transferred to nude mice and the recipient mice were challenged with SRV. One hundred percent of the reconstituted mice developed paralysis and died. Depletion of T cells from the donor spleen suspension prior to transfer abrogated the development of paralysis but did not prevent the deaths of the recipient animals. Mice receiving 10(8) rabies virus-immune spleen cells did not become paralyzed and did not die. Nude mice inoculated with either rabies virus-immune or normal mouse serum prior to and following SRV inoculation did not develop paralysis. Immune serum protected the mice, whereas animals inoculated with normal serum died. Central nervous system inflammatory responses in nude mice immunologically reconstituted with normal spleen cells were characterized by diffuse cellular infiltrates in the parenchyma and extensive perivascular cuffing. Perivascular infiltrates included CD8+ and CD4+ T lymphocytes and Mac-1+ macrophage-microglial cells. Inflammatory cells in the parenchyma were limited to CD8+ lymphocytes and Mac-1+ cells. These observations indicate that paralysis of SRV-infected mice is dependent on T lymphocytes. Whether injury leading to paralysis is mediated by T lymphocytes or by an influence of T lymphocytes on macrophage-microglial cells or other cells remains to be determined.",,"['Sugamata, M', 'Miyazawa, M', 'Mori, S', 'Spangrude, G J', 'Ewalt, L C', 'Lodmell, D L']",,,,
,PMC,Ribosomal frameshifting requires a pseudoknot in the Saccharomyces cerevisiae double-stranded RNA virus.,,PMC240802,,,"The large double-stranded RNA of the Saccharomyces cerevisiae (yeast) virus has two large overlapping open reading frames on the plus strand, one of which is translated via a -1 ribosomal frameshift. Sequences including the overlapping region, placed in novel contexts, can direct ribosomes to make a -1 frameshift in wheat germ extract, Escherichia coli and S. cerevisiae. This sequence includes a consensus slippery sequence, GGGUUUA, and has the potential to form a pseudoknot 3' to the putative frameshift site. Based on deletion analysis, a region of 71 nucleotides including the potential pseudoknot and the putative slippery sequence is sufficient for frameshifting. Site-directed mutagenesis demonstrates that the pseudoknot is essential for frameshifting.",,"['Tzeng, T H', 'Tu, C L', 'Bruenn, J A']",,,,
,PMC,Monoclonal antibodies to the spike protein of feline infectious peritonitis virus mediate antibody-dependent enhancement of infection of feline macrophages.,,PMC240797,,,"Antibody-dependent enhancement of virus infection is a process whereby virus-antibody complexes initiate infection of cells via Fc receptor-mediated endocytosis. We sought to investigate antibody-dependent enhancement of feline infectious peritonitis virus infection of primary feline peritoneal macrophages in vitro. Enhancement of infection was assessed, after indirect immunofluorescent-antibody labelling of infected cells, by determining the ratio between the number of cells infected in the presence and absence of virus-specific antibody. Infection enhancement was initially demonstrated by using heat-inactivated, virus-specific feline antiserum. Functional compatibility between murine immunoglobulin molecules and feline Fc receptors was demonstrated by using murine anti-sheep erythrocyte serum and an antibody-coated sheep erythrocyte phagocytosis assay. Thirty-seven murine monoclonal antibodies specific for the nucleocapsid, membrane, or spike proteins of feline infectious peritonitis virus or transmissible gastroenteritis virus were assayed for their ability to enhance the infectivity of feline infectious peritonitis virus. Infection enhancement was mediated by a subset of spike protein-specific monoclonal antibodies. A distinct correlation was seen between the ability of a monoclonal antibody to cause virus neutralization in a routine cell culture neutralization assay and its ability to mediate infection enhancement of macrophages. Infection enhancement was shown to be Fc receptor mediated by blockade of antibody-Fc receptor interaction using staphylococcal protein A. Our results are consistent with the hypothesis that antibody-dependent enhancement of feline infectious peritonitis virus infectivity is mediated by antibody directed against specific sites on the spike protein.",,"['Olsen, C W', 'Corapi, W V', 'Ngichabe, C K', 'Baines, J D', 'Scott, F W']",,,,
,PMC,Single amino acid changes in the viral glycoprotein M affect induction of alpha interferon by the coronavirus transmissible gastroenteritis virus.,,PMC240773,,,"Transmissible gastroenteritis virus, an enteropathogenic coronavirus of swine, is a potent inducer of alpha interferon (IFN-alpha) both in vitro and in vivo. Previous studies have shown that virus-infected fixed cells or viral suspensions were able to induce an early and strong IFN-alpha synthesis by naive lymphocytes. Two monoclonal antibodies directed against the viral membrane glycoprotein M (29,000; formerly E1) were found to markedly inhibit virus-induced IFN production, thus assigning to M protein a potential effector role in this phenomenon (B. Charley and H. Laude, J. Virol. 62:8-11, 1988). The present report describes the selection and characterization of a collection of 125 mutant viruses which escaped complement-mediated neutralization by two IFN induction-blocking anti-M protein monoclonal antibodies. Two of these mutants, designated H92 and dm49-4, were found to exhibit a markedly reduced interferogenic activity. IFN synthesis by lymphocytes incubated with purified suspensions of these mutants was 30- to 300-fold lower than that of the parental virus. The transcription of IFN-alpha genes following induction by each mutant was decreased proportionally, as evidenced by Northern (RNA) blot analysis. The sequence of the M gene of 20 complement-mediated neutralization-resistant mutants, including the 2 defective mutants, was determined by direct sequencing of genome RNA. Thirteen distinct amino acid changes were predicted, all located at positions 6 to 22 from the N terminus of the mature M protein and within the putative ectodomain of the molecule. Two substitutions, Thr-17 to Ile and Ser-19 to Pro, were assumed to generate the defective phenotypes of mutants dm49-4 and H92, respectively. The alteration of an Asn-Ser-Thr sequence in dm49-4 virus led to the synthesis of an M protein devoid of a glycan side chain, which suggests a possible involvement of this structure in IFN induction. Overall, these data supported the view that an interferogenic determinant resides in the N-terminal, exposed part of the molecule and provided further evidence for the direct role of M protein in the induction of IFN-alpha by transmissible gastroenteritis virus. The acronym VIP (viral interferogenic protein) is proposed as a designation for this particular class of proteins.",,"['Laude, H', 'Gelfi, J', 'Lavenant, L', 'Charley, B']",,,,
,PMC,An RNA pseudoknot and an optimal heptameric shift site are required for highly efficient ribosomal frameshifting on a retroviral messenger RNA.,,PMC48309,,,"Synthesis of the pol gene products of most retroviruses requires ribosomes to shift frame once or twice in the -1 direction while translating gag-pol mRNA. The viral signals for frameshifting include a heptanucleotide sequence on which the shift occurs and higher-order RNA structure just downstream of the shift site. We have made site-directed mutations in two stems (S1 and S2) of a putative RNA pseudoknot that begins 7 nucleotides 3' of the previously identified shift site (A AAA AAC) in the gag-pro region of mouse mammary tumor virus (MMTV) RNA. The mutants confirm the predicted structure, show that loss of either S1 or S2 impairs frameshifting, and exclude alternative RNA structures as significant for frameshifting. The importance of the MMTV pseudoknot has been further demonstrated by showing that shift sites from two other retroviruses function more efficiently in the position of the MMTV site than in their native contexts. However, the MMTV pseudoknot cannot promote detectable frameshifting in the absence of a recognizable upstream shift site. In addition, the species of tRNA that reads the second codon in the shift site appears to be a critical determinant, since changing the 7th nucleotide in the MMTV gag-pro shift site from C to A, U, or G severely impairs frameshifting.",,"['Chamorro, M', 'Parkin, N', 'Varmus, H E']",,,,
,PMC,"In vitro activity of pirodavir (R 77975), a substituted phenoxy-pyridazinamine with broad-spectrum antipicornaviral activity.",,PMC189235,,,"Pirodavir (R 77975) is the prototype of a novel class of broad-spectrum antipicornavirus compounds. Although its predecessor, R 61837, a substituted phenyl-pyridazinamine, was effective in inhibiting 80% of 100 serotypes tested (EC80) at concentrations above 32 micrograms/ml, pirodavir inhibits the same percentage of viruses at 0.064 micrograms/ml. Whereas R 61837 was active almost exclusively against rhinovirus serotypes of antiviral group B, pirodavir is broad spectrum in that it is highly active against both group A and group B rhinovirus serotypes. Pirodavir is also effective in inhibiting 16 enteroviruses, with an EC80 of 1.3 micrograms/ml. Susceptible rhinovirus serotypes were rendered noninfectious by direct contact with the antiviral compound. Their infectivity was not restored by dilution of virus-drug complexes, but was regained by organic solvent extraction of the compound for most serotypes. Neutralized viruses became stabilized to acid and heat, strongly suggesting a direct interaction of the compounds with viral capsid proteins. Mutants resistant to R 61837 (up to 85 times the MIC) were shown to bear some cross-resistance (up to 23 times the MIC) to the new compound, indicating that pirodavir also binds into the hydrophobic pocket beneath the canyon floor of rhinoviruses. Pirodavir acts at an early stage of the viral replication cycle (up to 40 min after infection) and reduces the yield of selected rhinoviruses 1,000- to 100,000-fold in a single round of replication. The mode of action appears to be serotype specific, since pirodavir was able to inhibit the adsorption of human rhinovirus 9 but not that of human rhinovirus 1A. Pirodavir is a novel capsid-binding antipicornavirus agent with potent in vitro activity against both group A and group B rhinovirus serotypes.",,"['Andries, K', 'Dewindt, B', 'Snoeks, J', 'Willebrords, R', 'van Eemeren, K', 'Stokbroekx, R', 'Janssen, P A']",,,,
,PMC,Seroconversion of pigs in contact with dogs exposed to canine coronavirus.,,PMC1263508,,,"In order to determine if canine coronavirus (CCV) could be transmitted to pigs, two dogs were inoculated orally with virulent CCV. After 24 h, the dogs were moved to an isolation room that contained three three-day-old pigs. A wire mesh fence, allowing close contact between the animals, separated the dogs from the pigs. The dogs and pigs were observed for 14 days for clinical signs of disease. Samples of blood were obtained from dogs and pigs immediately before the dogs were inoculated with virus and 14 and 28 days later. The dogs developed mild clinical signs of an infection, but the pigs remained normal throughout the observation period. The dogs shed CCV for eight days after exposure. All three pigs developed neutralizing antibodies against CCV and transmissible gastroenteritis virus by 14 days after they were exposed to the dogs.",,"['Woods, R D', 'Wesley, R D']",,,,
,PMC,Tracheal collapse in a Holstein heifer,,PMC1481158,,,,,"['Ashworth, Chris D.', 'Wallig, Matthew A.', 'Mirsky, Mike L.', 'Smith, Robert M.']",,,,
,PMC,Rapid detection and identification of avian infectious bronchitis virus.,,PMC265000,,,"A rapid and sensitive method for the detection and unambiguous typing of infectious bronchitis virus (IBV) is described. RNA was isolated from IBV-infected allantoic fluid and was transcribed into cDNA. This cDNA was amplified by the polymerase chain reaction. The polymerase chain reaction products were subsequently analyzed on an agarose gel. The presence of IBV-specific RNA in the allantoic fluid then allowed the amplification of a 438-bp DNA fragment from the nucleocapsid (N) gene. For the typing of IBV isolates, we used amplified double-stranded DNA as a template in a sequencing reaction. We report 360 bases of the N gene of 18 IBV isolates. The sequence of the N gene was different between serologically indistinguishable IBV strains and may be a valuable tool in epidemiologic studies. A phylogenetic tree that was based on the sequences obtained did not agree with trees that were based on other parts of the sequence, illustrating the high frequency of recombination between IBV strains.",,"['Zwaagstra, K A', 'van der Zeijst, B A', 'Kusters, J G']",,,,
,PMC,Immunological changes in cats with concurrent Toxoplasma gondii and feline immunodeficiency virus infections.,,PMC264990,,,"To examine the immunological changes in cats concurrently infected with feline immunodeficiency virus (FIV) and Toxoplasma gondii, kittens (four per group) were inoculated with FIV, T. gondii, both agents, or no pathogens. Blood mononuclear cells and plasma were collected weekly for lymphocyte assays and serology. At week 14, spleen and lymph node cells were used for lymphocyte assays; brains and mesenteric lymph nodes were used for isolation of T. gondii. More T. gondii organisms were present in tissues of the dually infected cats than in tissues of cats with toxoplasmosis alone. Two dually infected cats and one cat infected with T. gondii developed chorioretinitis. Spleen, lymph node, and blood mononuclear cells from dually infected cats had the greatest reduction in mitogenic responses. By week 3, cats infected with FIV underwent a decrease in the number of CD4 cells that was not changed by concurrent T. gondii infection; the number of CD8 cells increased only in cats infected with T. gondii alone. For cats infected with T. gondii, the responses of lymphocytes to T. gondii antigen were not affected by FIV infection; the responses to FIV antigen were negligible in all groups. Overall, this study indicates that FIV infection favors T. gondii proliferation. Also, the establishment of toxoplasmosis may enhance FIV-induced immunodeficiency and is likely to cause a more rapid disease progression than that from infection with FIV alone.",,"['Lin, D S', 'Bowman, D D', 'Jacobson, R H']",,,,
,PMC,Rapid and biologically safe diagnosis of African swine fever virus infection by using polymerase chain reaction.,,PMC264988,,,"In order to circumvent the need for infectious virus for the diagnosis of African swine fever (ASF), we established the polymerase chain reaction (PCR) technique for the detection of ASF virus (ASFV) DNA. A 740-bp fragment that originated from the conserved region of the viral genome was partially sequenced. From this sequence, four PCR primers and one oligonucleotide probe were designed and synthesized. A specific 640-bp PCR product was amplified by using oligonucleotides 1 and 5 as primers and extracts of the following samples as templates: organs and plasma obtained from ASFV-infected pigs, ASFV-infected cell cultures, and cloned DNA fragments containing the same conserved genomic region as that in the original 740-bp clone. No specific reaction products were observed in the corresponding controls. The identities of the PCR products were confirmed either by a second amplification with nested primers or by hybridization with a specific, biotinylated oligonucleotide probe. PCR proved to be a quicker and more sensitive method than virus isolation followed by the hemadsorption test when spleen and plasma samples from experimentally ASFV-infected pigs were tested. Furthermore, cloned virus DNA could be used as a positive control in the place of a live virus control. This is advantageous whenever the use of live virus is undesirable.",,"['Steiger, Y', 'Ackermann, M', 'Mettraux, C', 'Kihm, U']",,,,
,PMC,The central hydrophobic domain of the bovine papillomavirus E5 transforming protein can be functionally replaced by many hydrophobic amino acid sequences containing a glutamine.,,PMC238311,,,"The 44-amino-acid E5 transforming protein of bovine papillomavirus can induce growth transformation of cultured rodent fibroblast cell lines. Previous studies revealed that efficient transformation of mouse C127 cells by the E5 protein required a central core of hydrophobic amino acids and several specific carboxyl-terminal amino acids. Although a randomly derived sequence of hydrophobic amino acids could functionally replace the wild-type hydrophobic core, most such sequences could not. We show here that the conserved glutamine at position 17 in the hydrophobic domain is also important for transformation and that insertion of the glutamine can rescue the transforming activity of many but not all otherwise defective mutants containing random hydrophobic sequences. However, a class of mutants was identified that transform efficiently even in the absence of glutamine, demonstrating that the presence of this amino acid is not absolutely required for efficient transformation. E5 proteins containing the glutamine appear to display increased homodimer formation compared with mutant proteins lacking the glutamine, but this amino acid has no apparent effect on protein stability.",,"['Kulke, R', 'Horwitz, B H', 'Zibello, T', 'DiMaio, D']",,,,
,PMC,"Structure of DRE, a retrotransposable element which integrates with position specificity upstream of Dictyostelium discoideum tRNA genes.",,PMC364087,,,"Different Dictyostelium discoideum strains contain between 2 and 200 copies of a retrotransposable element termed DRE (Dictyostelium repetitive element). From the analysis of more than 50 elements, it can be concluded that DRE elements always occur 50 +/- 3 nucleotides upstream of tRNA genes. All analyzed clones contain DRE in a constant orientation relative to the tRNA gene, implying orientation specificity as well as position specificity. DRE contains two open reading frames which are flanked by nonidentical terminal repeats. Long terminal repeats (LTRs) are composed of three distinct modules, called A, B, and C. The tRNA gene-proximal LTR is characterized by one or multiple A modules followed by a single B module (AnB). With respect to the distal LTR, two different subforms of DRE have been isolated. The majority of isolated clones contains a distal LTR composed of a B module followed by a C module (BC), whereas the distal LTR of the other subform contains a consecutive array of a B module, a C module, a slightly altered A module, another B module, and another C module (BC.ABC). Full-length as well as smaller transcripts from DRE elements have been detected, but in comparison with the high copy number in D. discoideum strains derived from the wild-type strain NC4, transcription is rather poor.",,"['Marschalek, R', 'Hofmann, J', 'Schumann, G', 'Gösseringer, R', 'Dingermann, T']",,,,
,PMC,"A highly efficient, cell-free translation/translocation system prepared from Xenopus eggs.",,PMC329185,,,"We describe the use of a Xenopus laevis egg extract for the in vitro translation and post translational modification of membrane and secretory proteins. This extract is capable of the translation and segregation into membranes of microgram per millilitre levels of protein from added mRNAs. Signal sequences of segregated proteins are efficiently cleaved and appropriate N-linked glycosylation patterns are produced. The extract also supports the quantitative assembly of murine immunoglobulin heavy and light chains into tetramers, and two events which take place beyond the endoplasmic reticulum, mannose 6 phosphorylation of murine cathepsin D and O-linked glycosylation of coronavirus E1 protein, also occur, but at reduced efficiency. The stability of the membranes allows protease protection studies and quantitative centrifugal fractionation of segregated and unsegregated proteins to be performed. Conditions for the use of stored extract have also been determined.",,"['Matthews, G', 'Colman, A']",,,,
,PMC,Hygromycin B inhibits synthesis of murine coronavirus RNA.,,PMC245443,,,"The aminoglycoside hygromycin B inhibits the infection of mouse hepatitis virus (MHV) A59 both in vitro and in vivo. In probing the mechanism by which hygromycin B exerts its antiviral effect, we describe here studies which point to inhibition of viral RNA synthesis as the key step in virus replication which is affected by the drug. Cells which are infected with MHV do not take up higher levels of hygromycin B than do uninfected ones. Comparative assays of MHV replication and MHV protein synthesis in the presence of hygromycin B and another aminoglycoside, neomycin, indicate that hygromycin B is the more-effective antiviral agent and that its antiviral activity likely does not involve phosphoinositide-mediated processes such as those inhibited by neomycin.",,"['Macintyre, G', 'Woods, D E', 'Anderson, R']",,,,
,PMC,"Sequences within and adjacent to the transmembrane segment of alpha-2,6-sialyltransferase specify Golgi retention.",,PMC453089,,,"The glycosyltransferase alpha-2,6-sialyltransferase (ST) is a Type II membrane protein localized to the Golgi apparatus. The first 44 amino acids of this protein were able to specify Golgi retention of a fused marker protein, lysozyme. This section of ST contains a transmembrane segment which serves as a non-cleaved signal anchor. When lysozyme was fused to an equivalent region of a cell surface protein it now appeared on the cell surface. Analysis of chimeras between the two proteins revealed that the transmembrane segment of ST specifies Golgi retention. Furthermore, altering this segment in full-length ST results in the protein accumulating on the cell surface. However, the retaining effect of the transmembrane domain of ST is augmented by the presence of adjacent lumenal and cytoplasmic sequences from ST. If these sequences are spaced apart by a transmembrane domain of the same length as that of ST they too can specify Golgi retention. Thus retention in the Golgi of ST appears to involve recognition of an extended region of the protein within and on both sides of the bilayer.",,"Munro, S",,,,
,PMC,Detection of rodent coronaviruses in tissues and cell cultures by using polymerase chain reaction.,,PMC270434,,,"A polymerase chain reaction (PCR) method was developed for the detection of rodent coronaviruses in biological material by using reverse transcriptase and two primers which flanked an M gene sequence of 375 bp. PCR detected all of 11 different strains of mouse hepatitis virus (MHV) as well as rat sialodacryoadenitis virus but not bovine coronavirus or human coronavirus strains OC43 and 229E. The M gene sequences of bovine coronavirus and human coronavirus OC43 are homologous to that of MHV, but minor differences exist in the primer regions, preventing annealing of the primers. For detecting MHV-Y in tissue samples, PCR was faster than and at least as sensitive as either of the two bioassays (infant mouse bioassay and mouse antibody production test) currently used for MHV diagnostic purposes.",,"['Homberger, F R', 'Smith, A L', 'Barthold, S W']",,,,
,PMC,Chloroquine induces empty capsid formation during poliovirus eclipse.,,PMC250817,,,"The poliovirus capsid (160S) is modified during eclipse in HeLa cells, which results in at least three types of particles having sedimentation coefficients of 135, 110, and 80S. The lysosomotropic agent chloroquine redirected the production of eclipse products from 135 and 110S particles (containing RNA) to 80S particles (without RNA). The effect started at 5 microM and was fully developed with 20 microM chloroquine. Viral protein synthesis and virion production remained unaffected. The results show that chloroquine can redirect the processing of input virions without interfering with productive uncoating.",,"['Kronenberger, P', 'Vrijsen, R', 'Boeyé, A']",,,,
,PMC,"A conserved coronavirus epitope, critical in virus neutralization, mimicked by internal-image monoclonal anti-idiotypic antibodies.",,PMC250811,,,"Monoclonal antibody (MAb) 6A.C3 neutralizes transmissible gastroenteritis coronavirus (TGEV) and is specific for a conserved epitope within subsite Ac of the spike (S) glycoprotein of TGEV. Six hybridomas secreting anti-idiotypic (Ab2) MAbs specific for MAb 6A.C3 (Ab1) have been selected. All six MAbs inhibited the binding of Ab1 to TGEV and specifically cross-linked MAb1-6A.C3. Four of these hybridomas secreted gamma-type anti-idiotypic MAbs. The other two Ab2s (MAbs 9A.G3 and 9C.E11) were recognized by TGEV-specific antiserum induced in two species. This binding was inhibited by viruses of the TGEV group but not by serologically unrelated coronaviruses. These results indicate that MAb2-9A.G3 and MAb2-9C.E11 mimic an antigenic determinant present on the TGEV surface, and they were classified as beta-type (""internal-image"") MAbs. TGEV-binding Ab3 antiserum was induced in 100% of mice immunized with the two beta-type MAb2s and in 25 to 50% of mice immunized with gamma-type MAb2. Both beta- and gamma-type Ab2s induced neutralizing Ab3 antibodies in mice that were mainly directed to antigenic subsite Ac of the S protein.",,"['Suñé, C', 'Smerdou, C', 'Antón, I M', 'Abril, P', 'Plana, J', 'Enjuanes, L']",,,,
,PMC,Cloning of the mouse hepatitis virus (MHV) receptor: expression in human and hamster cell lines confers susceptibility to MHV.,,PMC250787,,,"The cellular receptor for murine coronavirus mouse hepatitis virus (MHV)-A59 is a member of the carcinoembryonic antigen (CEA) family of glycoproteins in the immunoglobulin superfamily. We isolated a cDNA clone (MHVR1) encoding the MHV receptor. The sequence of this clone predicts a 424-amino-acid glycoprotein with four immunoglobulinlike domains, a transmembrane domain, and a short intracytoplasmic tail, MHVR1 is closely related to the murine CEA-related clone mmCGM1 (Mus musculus carcinoembryonic antigen gene family member). Western blot (immunoblot) analysis performed with antireceptor antibodies detected a glycoprotein of 120 kDa in BHK cells stably transfected with MHVR1. This corresponds to the size of the MHV receptor expressed in mouse intestine and liver. Human and hamster fibroblasts transfected with MHVR1 became susceptible to infection with MHV-A59. Like MHV-susceptible mouse fibroblasts, the MHVR1-transfected human and hamster cells were protected from MHV infection by pretreatment with monoclonal antireceptor antibody CC1. Thus, the 110- to 120-kDa CEA-related glycoprotein encoded by MHVR1 is a functional receptor for murine coronavirus MHV-A59.",,"['Dveksler, G S', 'Pensiero, M N', 'Cardellichio, C B', 'Williams, R K', 'Jiang, G S', 'Holmes, K V', 'Dieffenbach, C W']",,,,
,PMC,New nucleotide sequence data on the EMBL File Server,,PMC329084,,,,,,,,,
,PMC,Inhibitory effects of recombinant human cystatin C on human coronaviruses.,,PMC245403,,,"Cystatin C, a potent inhibitor of cysteine proteases such as papain and cathepsin B, was examined for its effect on human coronaviruses OC43 and 229e. Both viruses were greater than 99% inhibited by 0.1 mM inhibitor. Endpoint titrations showed that inhibiting activity paralleled that of leupeptin, a serine and cysteine protease inhibitor, and indicated that 1 to 2 microM inhibitor, slightly above physiologic levels, was effective.",,"['Collins, A R', 'Grubb, A']",,,,
,PMC,Population dynamics of lymphocyte subsets in the central nervous system of rats with different susceptibility to coronavirus-induced demyelinating encephalitis.,,PMC1384652,,,"The inflammatory response in the central nervous system (CNS) of rats with differing susceptibility to demyelinating encephalitis induced by coronavirus MHV4 was characterized. Topographical maps showing the arrangement of infiltrating lymphocyte subsets in virus-infected tissue were developed by digital-image processing of immunohistologically stained CNS sections. The kinetics of the inflammatory process was evaluated by flow-cytometry on lymphocytes isolated from the CNS. Cumulative data obtained with these two techniques demonstrated the following features. In susceptible Lewis (LE) rats, viral antigens were disseminated throughout the CNS, including spinal cord. Onset as well as recovery from neurological disease was associated with a steep rise of infiltrating CD8+ T cells, which localized in close contact to virus-infected cells. Accompanying convalescence was a slight increase in B(OX33+) cells in the CNS and the accumulation of immunoglobulin-containing cells in the centre of virus-infected areas. In clinically resistant Brown Norway (BN) rats, virus-infected cells were mainly restricted to small periventricular foci and the extent of lymphocyte infiltration was never as high as that found at any time during the course of infection in LE rats. There were striking differences in the CD8+ T-cell population compared to LE rats. Cells of this phenotype were identified in virus-affected areas of BN rats only early after infection, and their infiltration profile revealed much lower quantities than in the CNS of susceptible LE rats. Although the population dynamics of B(OX33+) lymphocytes were comparable in BN and LE rats, as determined by flow-cytometry, less immunoglobulin-containing B cells were detected in virus-infected areas of BN rats.",,"['Dörries, R', 'Schwender, S', 'Imrich, H', 'Harms, H']",,,,
,PMC,The pathogenic role of virus-specific antibody-secreting cells in the central nervous system of rats with different susceptibility to coronavirus-induced demyelinating encephalitis.,,PMC1384651,,,"The humoral immune response in the central nervous system (CNS) of susceptible Lewis (LE) rats and resistant Brown Norway (BN) rats was analysed after intracerebral infection with the murine coronavirus JHM (MHV4). The subclinical course of the infection in BN rats was characterized by an early rise of neutralizing antibodies in the cerebrospinal fluid (CSF) 7 days post-infection. At this time in LE rats, neutralizing antibodies were not detectable in the CSF and the animals developed neurological signs of infection. Subsequently, LE rats recovered from disease. This process was accompanied by increasing titres of virus-neutralizing antibodies. Within the CNS parenchyma of both rat strains, equivalent numbers of IgM-secreting cells were detected. However, in BN rats, virus-specific IgG secreting cells appeared earlier and in higher numbers. Moreover, based on the size of zones of antibody secreted by single cells in the Spot-ELISA assay, it appeared that cells from BN rats secreted IgG antibody of higher affinity. These data suggest that early maturation of antiviral antibody responses in the resistant BN rat probably restricts the spread of viral infection to small foci within the CNS, resulting in a subclinical level of primary demyelination. In contrast, the absence of neutralizing antibodies in the susceptible LE rats favours spread of the virus throughout the CNS, resulting finally in severe neurological disease.",,"['Schwender, S', 'Imrich, H', 'Dörries, R']",,,,
,PMC,Frameshifting in gene 10 of bacteriophage T7.,,PMC209055,,,"Gene 10 of bacteriophage T7, which encodes the most abundant capsid protein, has two products: a major product, 10A (36 kDa), and a minor product, 10B (41 kDa). 10B is produced by frameshifting into the -1 frame near the end of the 10A coding frame and is incorporated into the capsid. The frameshift occurs at a frequency of about 10% and is conserved in bacteriophage T3. This study shows that sequences important to frameshifting include the originally proposed frameshift site, consisting of overlapping phenylalanine codons and the 3' noncoding region that includes the transcriptional terminator over 200 bases downstream of the frameshift site. The frameshift occurs at the overlapping phenylalanine codons as determined from peptide sequencing data. Complementation studies show that there is only a very weak phenotype associated with phage infections in which there is no 10A frameshifting. Capsids from such infections are devoid of 10B and are as stable as wild-type capsids.",,"['Condron, B G', 'Atkins, J F', 'Gesteland, R F']",,,,
,PMC,"Isolation, characterization, and serial propagation of a bovine group C rotavirus in a monkey kidney cell line (MA104).",,PMC270383,,,"A virus (designated the Shintoku strain) which was morphologically indistinguishable from group A rotaviruses was detected in the feces of adult cows with diarrhea in Japan. The virus contained 11 segments of double-stranded RNA and had an electrophoretic migration pattern in polyacrylamide gels similar to that of other group C rotaviruses (4-3-2-2). Feces containing the bovine virus reacted with antiserum to porcine group C rotavirus (Cowden strain) but not group A or B rotaviruses in immunoelectron microscopy. The virus was adapted to serial propagation in roller tube cultures of a rhesus monkey kidney cell line (MA104) by using high concentrations of trypsin. Evidence for viral replication in MA104 cell cultures was demonstrated by immunoelectron microscopy and indirect immunofluorescence by using antiserum to porcine group C rotavirus and by electrophoretic analysis of extracted viral double-stranded RNA. A significant antibody response against the isolate was detected in convalescent-phase sera of cows which excreted the virus: no increased antibody response to bovine group A rotavirus was observed. To our knowledge, this is the first isolation of a group C rotavirus from cattle.",,"['Tsunemitsu, H', 'Saif, L J', 'Jiang, B M', 'Shimizu, M', 'Hiro, M', 'Yamaguchi, H', 'Ishiyama, T', 'Hirai, T']",,,,
,PMC,The 5' end of coronavirus minus-strand RNAs contains a short poly(U) tract.,,PMC250348,,,"A radiolabeled oligodeoxynucleotide primer that anneals near the common 5' end of bovine coronavirus minus-strand RNAs was extended with reverse transcriptase, and a major product suggesting poly(U) tracts of 8 to 20 nucleotides was found. The extended primer molecules were ligated head to tail, amplified by the polymerase chain reaction, cloned, and sequenced, and poly(U) tracts of 9 to 26 nucleotides were found. Poly(A) tails of 100 to 130 nucleotides on the 3' end of coronavirus plus-strand mRNAs and genome must, therefore, be generated by a mechanism that uses only a short poly(U) template. This pattern contrasts with that of other cytoplasmic, polyadenylated, plus-strand animal RNA viruses which utilize a full-length poly(U) template for poly(A) synthesis.",,"['Hofmann, M A', 'Brian, D A']",,,,
,PMC,The S protein of bovine coronavirus is a hemagglutinin recognizing 9-O-acetylated sialic acid as a receptor determinant.,,PMC250319,,,"The S protein of bovine coronavirus (BCV) has been isolated from the viral membrane and purified by gradient centrifugation. Purified S protein was identified as a viral hemagglutinin. Inactivation of the cellular receptors by sialate 9-O-acetylesterase and generation of receptors by sialylation of erythrocytes with N-acetyl-9-O-acetylneuraminic acid (Neu5,9Ac2) indicate that S protein recognizes 9-O-acetylated sialic acid as a receptor determinant as has been shown previously for intact virions. The second glycoprotein of BCV, HE, which has been thought previously to be responsible for the hemagglutinating activity of BCV, is a less efficient hemagglutinin; it agglutinates mouse and rat erythrocytes, but in contrast to S protein, it is unable to agglutinate chicken erythrocytes, which contain a lower level of Neu5,9Ac2 on their surface. S protein is proposed to be responsible for the primary attachment of virus to cell surface. S protein is proposed to be responsible for the primary attachement of virus to cell surface receptors. The potential of S protein as a probe for the detection of Neu5,9Ac2-containing glycoconjugates is demonstrated.",,"['Schultze, B', 'Gross, H J', 'Brossmer, R', 'Herrler, G']",,,,
,PMC,"A system for study of coronavirus mRNA synthesis: a regulated, expressed subgenomic defective interfering RNA results from intergenic site insertion.",,PMC250269,,,"A system that exploits defective interfering (DI) RNAs of mouse hepatitis virus (MHV) for deciphering the mechanisms of coronavirus mRNA transcription was developed. A complete cDNA clone of MHV DI RNA containing an inserted intergenic region, derived from the area of genomic RNA between genes 6 and 7, was constructed. After transfection of the in vitro-synthesized DI RNA into MHV-infected cells, replication of genomic DI RNA as well as transcription of the subgenomic DI RNA was observed. S1 nuclease protection experiments, sequence analysis, and Northern (RNA) blotting analysis revealed that the subgenomic DI RNA contained the leader sequence at its 5' end and that the body of the subgenomic DI RNA started from the inserted intergenic sequence. Two subgenomic DI RNAs were synthesized after inserting two intergenic sites into the MHV DI RNA. Metabolic labeling of virus-specific protein in DI RNA replicating cells demonstrated that a protein was translated from the subgenomic DI RNA, which can therefore be considered a functional mRNA. Transfection study of gel-purified genomic DI RNA and subgenomic DI RNA revealed that the introduction of the genomic DI RNA, but not subgenomic DI RNA, into MHV-infected cells was required for synthesis of the subgenomic DI RNA. A series of deletion mutations in the intergenic site demonstrated that the sequence flanking the consensus sequence of UCUAAAC affected the efficiency of subgenomic DI RNA transcription and that the consensus sequence was necessary but not sufficient for the synthesis of the subgenomic DI RNA.",,"['Makino, S', 'Joo, M', 'Makino, J K']",,,,
,PMC,"Oligomerization, transport, and Golgi retention of Punta Toro virus glycoproteins.",,PMC250253,,,"We have investigated the oligomerization and intracellular transport of the membrane glycoproteins of Punta Toro virus, a member of the Phlebovirus genus of the family Bunyaviridae, which is assembled by budding in the Golgi complex. By using one- or two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, chemical cross-linking, and sucrose gradient centrifugation, we found that the majority of the G1 and G2 glycoproteins are assembled into noncovalently linked G1-G2 heterodimers. At the same time, a fraction of the G2 protein, possibly produced independently of the G1 protein, is assembled into G2 homodimers. Kinetic analysis indicates that heterodimerization occurs between newly synthesized G1 and G2 within 3 min after protein synthesis, and that the G1 and G2 glycoproteins are associated as dimeric forms both during transport and after accumulation in the Golgi complex. Analysis of a G1-truncated G2 mutant, which is also targeted to the Golgi complex, showed that these molecules also assemble into dimeric forms, which are linked by disulfide bonds. Both the G1-G2 heterodimer and the G2 homodimer were found to be able to exit from the endoplasmic reticulum. Differences in transport kinetics observed for the G1 and G2 proteins may be due to the differences in the transport efficiency between the G1-G2 heterodimer and the G2 homodimer from the endoplasmic reticulum to the Golgi complex. These and previous results (S.-Y. Chen, Y. Matsuoka, and R.W. Compans, Virology 183:351-365, 1991) suggest that Golgi retention of the G2 homodimer occurs by association with the G1-G2 heterodimer, whereas the Golgi targeting of the G1-G2 heterodimer occurs by a specific retention mechanism.",,"['Chen, S Y', 'Compans, R W']",,,,
,PMC,Transgenic mouse model for central nervous system demyelination.,,PMC361917,,,"A common feature of demyelinating diseases such as multiple sclerosis in humans and experimental autoimmune encephalomyelitis in rodents is the marked elevation in the expression of the major histocompatibility complex (MHC) antigens in the involved sites. By specific targeting of a syngeneic MHC class I gene to oligodendrocytes, we have generated transgenic mice which not only exhibit severe involuntary tremors and develop tonic seizures but also show extensive demyelination in both the brain and the spinal cord. The fact that demyelination in these mice occurs in the absence of immune infiltration dismisses an autoimmune involvement but suggests that the MHC class I antigens play a direct role in inducing disease. Our findings lend support to the possibility that demyelinating diseases are induced by infectious agents such as viruses which can either directly activate MHC gene expression in oligodendroglia or indirectly activate expression through the release by reactive T cells of gamma interferon in the brain.",,"['Yoshioka, T', 'Feigenbaum, L', 'Jay, G']",,,,
,PMC,Hygromycin B therapy of a murine coronaviral hepatitis.,,PMC245338,,,"Hepatitis caused by mouse hepatitis virus (MHV-A59), a murine coronavirus, is accompanied by direct infection and replication of virus within the liver. We demonstrate here that the aminoglycoside hygromycin B is able to eliminate MHV-A59 infection from mouse peritoneal macrophages and cultured liver cells in vitro and is also able to reduce levels of virus replication and necrotic liver foci in vivo.",,"['Macintyre, G', 'Curry, B', 'Wong, F', 'Anderson, R']",,,,
,PMC,The role of interferon alpha/beta in the induction of intestinal pathology in mice.,,PMC1384605,,,We have investigated the role of interferon-alpha/beta (IFN-alpha/beta) and IFN-dependent effector cells in causing enteropathy in mice. The IFN-inducer polyinosinic:polycytydylic acid (poly I:C) augmented the natural killer (NK) cell activation normally seen in neonatal (CBA x BALB/c)F1 mice with graft-versus-host reaction (GVHR) and exacerbated the systemic and intestinal consequences of GVHR. Poly I:C itself produced a similar pattern of intestinal pathology when administered to normal mice. The effects of poly I:C on NK cell activity and intestinal architecture in normal mice could be reproduced by a single injection of purified IFN-alpha/beta and the intestinal lesions caused by IFN-alpha/beta were prevented by in vivo depletion of NK cells with anti-asialo GM1. These results indicate that IFN-alpha/beta may play an important role in immunologically mediated enteropathies by virtue of its ability to activate NK cells.,,"['Garside, P', 'Felstein, M V', 'Green, E A', 'Mowat, A M']",,,,
,PMC,Persistent cryptosporidiosis in horses with severe combined immunodeficiency.,,PMC258958,,,"Cryptosporidial infections were established in five young foals with severe combined immunodeficiency following oral administration of 10(8) Cryptosporidium parvum oocysts. All foals shed oocysts (average of 8 x 10(6) to 2 x 10(8)/g of feces) until death. Inflammation and C. parvum organisms were observed in the common bile duct, duodenum, jejunum, and ileum. Since foals with severe combined immunodeficiency lack functional T and B lymphocytes and are incapable of antigen-specific immune responses, they are well suited for evaluating the pathogenesis and treatment of persistent cryptosporidiosis.",,"['Bjorneby, J M', 'Leach, D R', 'Perryman, L E']",,,,
,PMC,Mouse hepatitis virus S RNA sequence reveals that nonstructural proteins ns4 and ns5a are not essential for murine coronavirus replication.,,PMC249076,,,"Genes 4 and 5 of mouse hepatitis virus (MHV) are known to encode nonstructural proteins ns4, ns5a, and ns5b, whose function is unknown. In this study, we demonstrated that one of the MHV strains, MHV-S, did not synthesize mRNA 4 and made a smaller mRNA 5. Sequence analysis showed that the transcription initiation site for gene 4 of MHV-S was mutated from the consensus UCUAAAC to UUUAAAC, consistent with the idea that mutations in this region abolish mRNA synthesis. Furthermore, within gene 5 there were deletions totaling 307 nucleotides which deleted almost all of open reading frame 5a, but preserved open reading frame 5b of gene 5. Comparison of the growth of MHV-S with other MHV strains in DBT cells revealed no significant growth defect in MHV-S. These results suggest that ns4 and ns5a are not essential for viral replication in tissue culture cells, and thus join gene 2 and the hemagglutinin-esterase (HE) gene as nonessential viral genes in MHV.",,"['Yokomori, K', 'Lai, M M']",,,,
,PMC,Nucleotide sequence and expression of the capsid protein gene of feline calicivirus.,,PMC249032,,,"The sequence of the 3'-terminal 2,486 bases of the feline calicivirus (FCV) genome was determined. This region of the FCV genome, from which the 2.4-kb subgenomic RNA is derived, contained two open reading frames. The larger open reading frame, found in the 5' end of the subgenomic mRNA, contained 2,004 bases encoding a polypeptide of 73,467 Da. The smaller open reading frame, encoded in the 3' end of the mRNA, was composed of 318 bases, encoding a polypeptide of 12,185 Da. The AUG initiation codon of the second open reading frame overlapped the UGA termination codon of the first, with the sequence AUGA. The nucleotide sequence of the region containing this overlap resembles the -1 frameshift sequences of the retroviruses. The 5' end of the 2.4-kb subgenomic RNA was mapped by primer extension analysis. There were two apparent transcription initiation points, both of which were 5' to the AUG initiation codon of the large open reading frame. Transcription from these sites yielded RNA transcripts with 5' nontranslated leader regions of 17 and 18 bases. The total length of the 2.4-kb subgenomic RNA was 2,375 bases (from the 5'-most start site) excluding the poly(A) tail. Edman degradation of the purified capsid protein of FCV showed that the capsid protein was encoded by the large open reading frame. Western immunoblot analysis of FCV-infected cells using a feline anti-FCV antiserum demonstrated that translation of the capsid protein was detectable at 3 h postinfection and continued to accumulate until 8 h postinfection, the last time examined.",,"['Neill, J D', 'Reardon, I M', 'Heinrikson, R L']",,,,
,PMC,A bovine papillomavirus E1-related protein binds specifically to bovine papillomavirus DNA.,,PMC249011,,,"The E1 open reading frame of bovine papillomavirus (BPV) was expressed as a RecA-E1 fusion protein in Escherichia coli. The bacterially expressed RecA-E1 protein exhibited sequence-specific DNA binding activity; strong binding to the region from nucleotides 7819 to 93 on the BPV genome (designated region A) and weak binding to the adjacent region from nucleotides 7457 to 7818 (region B) were observed. The interaction between the BPV-derived RecA-E1 protein and region A appeared to be highly specific for BPV DNA, as no comparable binding was detected with heterologous papillomavirus DNAs. Binding to region A was eliminated by digestion of region A at the unique HpaI site, which suggests that the RecA-E1 binding site(s) was at or near the HpaI recognition sequence. Binding to region B but not region A was observed when nuclear extracts from ID13 cells were used as a source of E1 proteins. The absence of region A binding by ID13 extracts may reflect a negative regulation of E1 DNA binding activity.",,"['Wilson, V G', 'Ludes-Meyers, J']",,,,
,PMC,Prophylactic intranasal alpha 2 interferon and viral exacerbations of chronic respiratory disease.,,PMC463387,,,"BACKGROUND As respiratory virus infections often lead to exacerbations of chronic bronchitis and asthma an effective antiviral drug may be helpful in such patients. Alpha 2 interferon has been shown to give protection against rhinovirus infections in field studies. METHODS Patients with chronic respiratory disease exposed to close contacts with symptoms of upper respiratory tract infection were randomly allocated to receive nasal sprays of recombinant alpha 2 interferon (3 x 10(6) IU) or placebo twice daily for five days. Of the 123 patients recruited into the study, 69 took 117 courses of medication; 11 courses were excluded from analysis. RESULTS No important side effects were recorded and the incidence of possible adverse effects was similar in the two groups. Interferon treatment did not reduce the number or severity of symptomatic episodes; 11 of 48 patients given interferon and 16 of 58 given placebo developed lower respiratory symptoms. There were no differences in mean symptom scores (51 interferon and 52 placebo), number of symptomatic days (3.3 interferon and 5.0 placebo), peak flow values, number of general practitioner consultations, or use of antibiotics. CONCLUSION Alpha 2 interferon 3 x 10(6) IU taken twice daily for five days does not protect patients with chronic respiratory disease from exacerbations after they have been in contact with an upper respiratory tract infection.",,"['Wiselka, M J', 'Nicholson, K G', 'Kent, J', 'Cookson, J B', 'Tyrrell, D A']",,,,
,PMC,Localization of a T-cell epitope within the nucleocapsid protein of avian coronavirus.,,PMC1384663,,,"In a previous study, two murine T-cell hybridomas generated after immunization with infectious bronchitis virus (IBV) were shown to be responsive to the internally localized viral nucleocapsid protein. In the present study, the antigenic determinants were mapped using recombinant expression products and synthetic peptides. Both hybridomas recognized the region spanning amino acid residues 71 to 78 of the nucleocapsid protein. The experimentally determined epitope corresponded with predicted motifs. Both an I-Ed binding motif and a predicted cleavage site for the aspartyl protease cathepsin D were contained within the sequence. The epitope was shown to prime cellular immune responses to IBV in the chicken.",,"['Boots, A M', 'Kusters, J G', 'van Noort, J M', 'Zwaagstra, K A', 'Rijke, E', 'van der Zeijst, B A', 'Hensen, E J']",,,,
,PMC,Mechanisms of viral pathogenesis. Distinct forms of reoviruses and their roles during replication in cells and host.,,PMC295447,,,,,"['Nibert, M L', 'Furlong, D B', 'Fields, B N']",,,,
,PMC,Reactivity of monoclonal antibodies to the 41-kilodalton protein of porcine group C rotavirus with homologous and heterologous rotavirus serogroups in immunofluorescence tests.,,PMC270259,,,"Three monoclonal antibodies (MAbs) to porcine group C rotavirus immunoprecipitated the major inner capsid protein (41 kDa) but failed to precipitate group A rotavirus proteins. In immunofluorescence tests of rotavirus-infected cell cultures or pig intestines, the MAbs recognized porcine and bovine group C rotaviruses but not group A or B rotaviruses. These MAbs may recognize the group C rotavirus counterpart to VP6 of group A rotaviruses and may be useful as diagnostic reagents.",,"['Ojeh, C K', 'Jiang, B M', 'Tsunemitsu, H', 'Kang, S Y', 'Weilnau, P A', 'Saif, L J']",,,,
,PMC,A nested set of eight RNAs is formed in macrophages infected with lactate dehydrogenase-elevating virus.,,PMC248981,,,"Total RNA was extracted from primary cultures of mouse macrophages isolated from 10-day-old mice 6 to 12 h postinfection with lactate dehydrogenase-elevating virus (LDV). Poly(A)+ RNA was extracted from spleens of 18-h LDV-infected mice. The RNAs were analyzed by Northern (RNA) blot hybridization with a number of LDV-specific cDNAs as probes. A cDNA representing the nucleocapsid protein (VP-1) gene located at the 3' terminus of the viral genome (E. K. Godeny, D. W. Speicher, and M. A. Brinton, Virology 177:768-771, 1990) hybridized to viral genomic RNA of about 13 kb plus seven subgenomic RNAs ranging in size from about 1 to about 3.6 kb. Two other cDNA clones hybridized only to the four or five largest subgenomic RNAs, respectively. In contrast, two cDNAs encoding continuous open reading frames with replicase and zinc finger motifs hybridized only to the genomic RNA. The replicase motif exhibited 75% amino acid identity to that of the 1b protein of equine arteritis virus (EAV) and 44% amino acid identity to those of the 1b proteins of coronaviruses and Berne virus. Combined, the results indicate that LDV replication involves formation of a 3'-coterminal-nested set of mRNAs as observed for coronaviruses and toroviruses as well as for EAV, with which LDV shares many other properties. Overall, LDV, like EAV, possesses a genome organization resembling that of the coronaviruses and toroviruses. However, EAV and LDV differ from the latter in the size of their genomes, virion size and structure, nature of the structural proteins, and symmetry of the nucleocapsids.",,"['Kuo, L L', 'Harty, J T', 'Erickson, L', 'Palmer, G A', 'Plagemann, P G']",,,,
,PMC,Infection by coronavirus JHM of rat neurons and oligodendrocyte-type-2 astrocyte lineage cells during distinct developmental stages.,,PMC248965,,,"Primary telencephalic cultures derived from neonatal Wistar Furth rats were able to support the growth of coronavirus JHM if a viable neuronal population was maintained. This occurred under serum-free defined, but not serum-supplemented, growth conditions. The importance of neurons in establishing infections in mixed cultures was confirmed by immunocytochemical and electron microscopic studies. Glia, although more abundant than neurons in these cultures, were less frequently infected during the initial 48 h postinoculation. The two glial lineages present in mixed telencephalic cultures were separated into type-1 astrocytes and oligodendrocyte-type-2 astrocyte (O-2A) lineage cells and individually assessed for their ability to support virus growth. Infection could not be established in type-1 astrocytes regardless of the culture conditions employed, consistent with our previous study (S. Beushausen and S. Dales, Virology 141:89-101, 1985). In contrast, infections could be initiated in selected O-2A lineage cells grown in serum-free medium. Virus multiplication was however significantly reduced by preconditioning the medium with mixed telencephalic or enriched type-1 astrocyte cultures, suggesting that intercellular interactions mediated by soluble factor(s) can influence the infectious process in O-2A lineage cells. This presumption was supported by eliciting similar effects with basic fibroblast growth factor and platelet-derived growth factor, two central nervous system cytokines known to control O-2A differentiation. The presence of these cytokines, which synergistically block O-2A cells from differentiating into oligodendrocytes was correlated with specific and reversible resistance to JHM virus (JHMV) infection. These data, combined with our finding that accelerated terminal differentiation of the oligodendrocyte phenotype confers resistance to JHMV (Beushausen and Dales, Virology, 1985), suggest that the permissiveness of O-2A cells for JHMV is restricted to a discrete developmental stage.",,"['Pasick, J M', 'Dales, S']",,,,
,PMC,In vivo accumulation of a turnip crinkle virus defective interfering RNA is affected by alterations in size and sequence.,,PMC248912,,,"Turnip crinkle virus is one of several single-stranded RNA plant viruses associated with defective interfering (DI) RNAs. A complete cDNA copy of a 344-base DI RNA (DI RNA G) was cloned downstream from a T7 RNA polymerase promoter. Transcripts synthesized in vitro were infectious when inoculated with helper virus on turnip plants. Studies of the infectivity of DI transcripts containing deletions, insertions, and single-base changes suggest that (i) in general, only the 5' two-thirds of the molecule can tolerate mutations; (ii) between 52 and 67 bases of terminal 5' sequence are required for infectivity; (iii) nucleotides in positions 68 to 138 are not specifically involved in RNA infectivity; (iv) DI RNA G molecules smaller than 327 bases are not amplified efficiently in plants.",,"['Li, X H', 'Simon, A E']",,,,
,PMC,Annual Review of Microbiology,,PMC2399123,,,,,"Wise, R.",,,,
,PMC,High-level ribosomal frameshifting directs the synthesis of IS150 gene products.,,PMC328623,,,"IS150 contains two tandem, out-of-phase, overlapping genes, ins150A and ins150B, which are controlled by the same promoter. These genes encode proteins of 19 and 31 kD, respectively. A third protein of 49 kD is a transframe gene product consisting of domains encoded by both genes. Specific -1 ribosomal frameshifting is responsible for the synthesis of the large protein. Expression of ins150B also involves frameshifting. The IS150 frameshifting signals operate with a remarkably high efficiency, causing about one third of the ribosomes to switch frame. All of the signals required for this process are encoded in a 83-bp segment of the element. The heptanucleotide A AAA AAG and a potential stem-loop-forming sequence mark the frameshifting site. Similar sequence elements are found in -1 frameshifting regions of bacterial and retroviral genes. A mutation within the stem-loop sequence reduces the rate of frameshifting by about 80%. Artificial transposons carrying this mutation transpose at a normal frequency, but form cointegrates at a approximately 100-fold reduced rate.",,"['Vögele, K', 'Schwartz, E', 'Welz, C', 'Schiltz, E', 'Rak, B']",,,,
,PMC,Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system.,,PMC52311,,,"In addition to the major population of infiltrating leukocytes recovered from inflamed rat central nervous system (CNS), all of which expressed high levels of leukocyte common antigen CD45, many cells were coisolated that were MRC OX42+ (complement receptor 3/CD11b) but expressed low-to-moderate levels of CD45 and major histocompatibility complex (MHC) class I molecules. Most cells from normal CNS, in contrast, lay within this latter, CD45low population. From previous in situ immunohistochemical studies, the fortuitously isolated CD45low cells were probably resident (ramified) microglia. Using irradiation chimeras, we show that resident microglia respond to inflammation by upregulating CD45, CD4, and MHC class I molecules with a minority of these cells increasing their expression of MHC class II molecules. A 3- to 4-fold increase in the number of microglia isolated from inflamed CNS provided indirect evidence that the cells had proliferated. In normal CNS, a very small population of blood-derived CD45high-expressing cells are present; most MHC class II expression is associated with these few cells and not with the resident microglia.",,"['Sedgwick, J D', 'Schwender, S', 'Imrich, H', 'Dörries, R', 'Butcher, G W', 'ter Meulen, V']",,,,
,PMC,Evidence that a downstream pseudoknot is required for translational read-through of the Moloney murine leukemia virus gag stop codon.,,PMC52219,,,"Approximately 5% of the ribosomes translating the gag gene of murine leukemia viruses read through the UAG terminator and translate the in-frame pol gene to produce the gag-pol fusion polyprotein, the sole source of the pol gene products. We show that a pseudoknot located eight nucleotides 3' of the UAG codon in the Moloney murine leukemia virus is required for read-through. This requirement is markedly different from that known to be involved in other cases of read-through but surprisingly similar to some stimulatory sequences known to promote ribosomal frameshifting.",,"['Wills, N M', 'Gesteland, R F', 'Atkins, J F']",,,,
,PMC,"A brief review of infectious and parasitic diseases of wapiti, with emphasis on western Canada and the northwestern United States",,PMC1481009,,,"In this paper I review diseases reported in both captive and free-ranging wapiti in western North America, with some reference to diseases in captive red deer in Great Britain, Europe, New Zealand, and eastern North America. With the exception of coronavirus in neonates, few viral agents are reported to cause serious disease losses in wapiti in North America at this time. Bacterial diseases of current significance include brucellosis (focus in Wyoming), clostridial diseases, coliform enteritis of neonates, pasteurellosis, and necrobacillosis. The endoparasites most likely to be seen causing lesions in wapiti of western North America are lungworm (Dictyocaulus viviparus), arterial worm (Elaeophora schneideri), and, possibly, liver fluke (Fascioloides magna). Ectoparasites of importance to wapiti are Psoroptes cervinus and Dermacentor albipictus. Nutritional diseases are not covered in this review.",,"Smits, Judit E.G.",,,,
,PMC,Chromatographic purification and characterization of antigens A and D from Mycobacterium paratuberculosis and their use in enzyme-linked immunosorbent assays for diagnosis of paratuberculosis in sheep.,,PMC270180,,,"The protein antigens A and D were purified from culture filtrates and sonic extracts of laboratory strains of Mycobacterium paratuberculosis by salt precipitation and chromatography. The characterization of antigen A is shown here, and both antigens were evaluated along with lipoarabinomannan antigen in indirect enzyme-linked immunosorbent assays (ELISA) for the serodiagnosis of ovine paratuberculosis. After anion-exchange (DEAE-5PW) and hydrophobic (phenyl-5PW) chromatography using high-performance liquid chromatography, antigen A showed a prominant band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) at 31 kDa with small amounts of low-molecular-mass proteins but with no evidence of antigen D. A single precipitin arc was evident with purified antigen A in crossed immunoelectrophoresis. The determination of the N-terminal amino acid sequence showed a high degree of homology between the 31-kDa component of antigen A and antigens of the BCG85 complex of Mycobacterium bovis BCG, a total of 24 of 26 residues being identical to those of BCG85C. A prominant SDS-PAGE band at 400 kDa and a single crossed-immunoelectrophoresis arc was also evident for antigen D after gel filtration (Sephacryl S-200), anion-exchange (DEAE-Sephacel), and concanavalin A-Sepharose affinity chromatography. By ELISA, purified antigen A detected antibody in the sera of 18 of 22 paratuberculosis-infected sheep (82% sensitivity), whereas the purified antigen D detected antibody in all 22 infected animals (100% sensitivity). Combined ELISA results showed increased specificity with some loss in sensitivity.",,"['Sugden, E A', 'Brooks, B W', 'Young, N M', 'Watson, D C', 'Nielsen, K H', 'Corner, A H', 'Turcotte, C', 'Michaelides, A', 'Stewart, R B']",,,,
,PMC,Generation and analysis of nonhomologous RNA-RNA recombinants in brome mosaic virus: sequence complementarities at crossover sites.,,PMC248849,,,"All three single-stranded RNAs of the brome mosaic virus (BMV) genome contain a highly conserved, 193-base 3' noncoding region. To study the recombination between individual BMV RNA components, barley plants were infected with a mixture of in vitro-transcribed wild-type BMV RNAs 1 and 2 and an RNA3 mutant that carried a deletion near the 3' end. This generated a population of both homologous and nonhomologous 3' recombinant BMV RNA3 variants. Sequencing revealed that these recombinants were derived by either single or double crossovers with BMV RNA1 or RNA2. The primary sequences at recombinant junctions did not show any similarity. However, they could be aligned to form double-stranded heteroduplexes. This suggested that local hybridizations among BMV RNAs may support intermolecular exchanges.",,"['Bujarski, J J', 'Dzianott, A M']",,,,
,PMC,The antigen of hepatitis delta virus: examination of in vitro RNA-binding specificity.,,PMC248837,,,"The only known protein of hepatitis delta virus (HDV), the delta antigen, is found both within virus particles and within the nucleus of the infected cell, where it has one or more roles essential for RNA genome replication. Others have demonstrated that the antigen has the ability, in vitro, to specifically bind HDV RNA species. We report a further examination of this phenomenon, using partially purified recombinant protein, expressed as a fusion with the staphylococcal protein A. From Northwestern (RNA-immunoblot) analyses with both complete and various subdomains of HDV genomic and antigenomic RNAs, we found that a necessary feature for specific binding was that the RNA be able to fold to some extent into the so-called rodlike structure; this structure is a predicted intramolecular partial base-pairing of the circular RNA, with about 70% of all bases involved, so as to produce an unbranched rodlike structure. Six different subregions of the HDV rodlike structure, three on the genomic RNA and three on its complement, the antigenomic RNA, were tested and found to be sufficient for antigen binding. However, features in addition to the rodlike structure may also be necessary for specific binding, because we found that a similar structure present in the RNA of the potato spindle tuber viroid did not allow binding.",,"['Chao, M', 'Hsieh, S Y', 'Taylor, J']",,,,
,PMC,Recombination between Sindbis virus RNAs.,,PMC248832,,,"The genome (49S RNA) of Sindbis virus is a positive-strand RNA of 11.7 kb that consists of two domains. The 5' two-thirds of the RNA codes for the proteins required for replication and transcription of the RNA. The 3' one-third codes for the structural proteins. The latter are translated from a 26S subgenomic RNA identical in sequence to the 3' one-third of the genome. The 26S RNA is transcribed by initiation from an internal promoter that spans the junction between the nonstructural and structural genes. We have used Sindbis virus RNAs transcribed from cloned cDNAs to demonstrate recombination between Sindbis virus RNAs in cultured cells. Several different combinations of deleted or mutationally altered RNAs gave rise to infectious recombinants. In 7 of 10 different crosses, the infectious recombinant RNAs were larger than wild-type 49S RNA. We sequenced the recombinant RNAs in the region spanning the junction between the nonstructural and structural protein genes from five different crosses. In three of the crosses, this is the only region within which recombination could have taken place to produce an infectious 49S RNA. Recombination also occurred in this region in the other two crosses. The recombinant RNAs were distinct from wild-type RNA and from each other. All contained sequence insertions derived from the parental RNAs. One contained a deletion and a rearrangement, and one also contained a stretch of 11 nucleotides not found in the Sindbis virus genome. When each of the parental RNAs contained a functional subgenomic RNA promoter, both promoters were present and functional in the recombinant RNA. Those recombinants with large sequence insertions showed evidence of evolution toward the wild-type single-junction RNA.",,"['Weiss, B G', 'Schlesinger, S']",,,,
,PMC,Monoclonal antibody-defined epitope map of expressed rubella virus protein domains.,,PMC248828,,,"An expanded library of murine monoclonal antibodies (MAbs) was generated by infecting BALB/C mice with the Therien strain of rubella virus (RV) and selecting secreting hybrids by enzyme-linked immunosorbent assay (ELISA) using purified virion targets. A panel of plasmids containing specified RV cDNA fragments was also constructed by using a variety of strategies with pGE374- and pGE374-derived expression vectors. Hybrid RecA-RV-beta-galactosidase (LacZ)- or RecA-RV-truncated LacZ-containing proteins collectively representing the entire open reading frame of the structural proteins of RV were overexpressed in Escherichia coli. Bacterial lysates were then probed by ELISA with selected MAbs and by immunoblot following separation by electrophoresis under denaturing conditions. With this approach, MAbs that appeared to react with linear determinants defined epitopes localized within the following domains: MAbs C-1, C-2, and C-8 bind epitopes within the predicted amino-terminal 21 amino acids of the capsid region C9 to C29; MAb C-9 binds to a domain bounded by C64 and C97; MAbs E2-1 through E2-6 bind to the E2 glycoprotein backbone region from E2(1) to E2(115); MAbs E1-18 and E1-20 bind to the E1 glycoprotein region from E1(202) to E1(283). MAb E1-18 neutralizes RV infectivity; MAb E1-20 neutralizes infectivity and modestly inhibits hemagglutination. Analyses with selected synthetic peptides have confirmed several of the molecular domains deduced with the expressed proteins. These plasmid constructions and peptides have proven useful in beginning to unravel the molecular organization of several antigenic sites of this human pathogen.",,"['Wolinsky, J S', 'McCarthy, M', 'Allen-Cannady, O', 'Moore, W T', 'Jin, R', 'Cao, S N', 'Lovett, A', 'Simmons, D']",,,,
,PMC,Human influenza virus hemagglutinin with high sensitivity to proteolytic activation.,,PMC241346,,,"To examine the prerequisites for cleavage activation of the hemagglutinin of human influenza viruses, a cDNA clone obtained from strain A/Port Chalmers/1/73 (serotype H3) was subjected to site-directed mutagenesis and expressed in CV-1 cells by using a simian virus 40 vector. The number of basic residues at the cleavage site, which consists of a single arginine with wild-type hemagglutinin, was increased by inserting two, three, or four additional arginines. Like wild-type hemagglutinin, mutants with up to three additional arginines were not cleaved in CV-1 cells, but insertion of four arginines resulted in activation. When the oligosaccharide at asparagine 22 of the HA1 subunit of the hemagglutinin was removed by site-directed mutagenesis of the respective glycosylation site, only three inserted arginines were required to obtain cleavage. Mutants containing a series of four basic residues were also generated by substituting arginine for uncharged amino acids immediately preceding the cleavage site. The observation that these mutants were not cleaved, even when the carbohydrate at asparagine 22 of HA1 was absent, underscores the fact that the basic peptide had to be generated by insertion to obtain cleavage. The data show that the hemagglutinin of a human influenza virus can acquire high cleavability, a property known to be an important determinant for the pathogenicity of avian influenza viruses. Factors important for cleavability are the number of basic residues at the cleavage site, the oligosaccharide at asparagine 22, and the length of the carboxy terminus of HA1.",,"['Ohuchi, R', 'Ohuchi, M', 'Garten, W', 'Klenk, H D']",,,,
,PMC,Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins.,,PMC51911,,,"The receptor for mouse hepatitis virus (MHV), a murine coronavirus, is a 110- to 120-kDa glycoprotein on intestinal brush border membranes and hepatocyte membranes. The N-terminal 25-amino acid sequence of immunoaffinity-purified MHV receptor was identical to the predicted mature N termini of two mouse genes related to human carcinoembryonic antigen (CEA) and was strongly homologous to the N termini of members of the CEA family in humans and rats. Polyclonal antibodies to human CEA recognized the immunoaffinity-purified MHV receptor and the MHV receptor in liver membranes and intestinal brush border membranes from MHV-susceptible mouse strains. In membranes from MHV-resistant SJL/J mice, the anti-CEA antibodies recognized a homologous glycoprotein that failed to bind MHV. The MHV receptor glycoprotein was detected in membranes of BALB/c colon, small intestine, and liver, which are the principal targets for MHV replication in vivo. The MHV receptor glycoprotein resembled members of the human CEA family in molecular weight, acidic pI, extensive glycosylation, solubility in perchloric acid, and tissue distribution. Thus, the MHV receptor is, to our knowledge, the first member of the CEA family of glycoproteins to be identified as a virus receptor.",,"['Williams, R K', 'Jiang, G S', 'Holmes, K V']",,,,
,PMC,Immunoglobulin class- and subclass-specific responses to Mycoplasma pulmonis in sera and secretions of naturally infected Sprague-Dawley female rats.,,PMC257984,,,"Mycoplasma pulmonis causes chronic murine respiratory mycoplasmosis and genital disease in rats. Specific immunoglobulin M (IgM), IgA, and IgG and its subclasses present in sera and tracheal and uterine lavage samples from 36 naturally infected Sprague-Dawley female rats were tested for reactivity with M. pulmonis in an enzyme-linked immunosorbent assay. Ten specific-pathogen-free Sprague-Dawley female rats served as the negative controls. Tracheal and uterine lavage samples were cultured quantitatively for M. pulmonis. M. pulmonis was isolated from the trachea (35 of 36) and uterus (17 of 36) of naturally infected rats; all rats were infected in at least one of the two sites cultured. M. pulmonis was not isolated from any control rat. There was a significant difference in levels of specific antibody of all classes except IgG2c between control and naturally infected animals (P less than 0.001 for IgM, IgG, IgG1, and IgG2a; P less than 0.002 for IgG2b; and P less than 0.02 for IgA). There was no correlation between numbers of M. pulmonis cells isolated and the amount or class of antibody measured in serum or tracheal lavage specimens. The predominant antibodies to M. pulmonis found in the sera of naturally infected rats were IgG and IgM. The IgG2a subclass was responsible for the majority of IgG-positive animals. There were no differences between rats which were positive by culture for M. pulmonis in the uterus (U+) and rats which were negative by culture for M. pulmonis in the uterus (U-) with respect to distribution or amount of antibody classes and subclasses in the serum. However, tracheal wash samples from U+ rats had significantly higher (P less than 0.03) levels of specific IgG1 and IgG2a than those from U- rats. Conversely, IgG2a was present in higher levels in pooled uterine lavage specimens from U- rats than in those from U+ rats.",,"['Brown, M B', 'Reyes, L']",,,,
,PMC,"Genetic analysis of porcine respiratory coronavirus, an attenuated variant of transmissible gastroenteritis virus.",,PMC240999,,,"The genome and transcriptional pattern of a newly identified respiratory variant of transmissible gastroenteritis virus were analyzed and compared with those of classical enterotropic transmissible gastroenteritis virus. The transcriptional patterns of the two viruses indicated that differences occurred in RNAs 1 and 2(S) and that RNA 3 was absent in the porcine respiratory coronavirus (PRCV) variant. The smaller RNA 2(S) of PRCV was due to a 681-nucleotide (nt) deletion after base 62 of the PRCV peplomer or spike (S) gene. The PRCV S gene still retained information for the 16-amino-acid signal peptide and the first 6 amino acid residues at the N terminus of the mature S protein, but the adjacent 227 residues were deleted. Two additional deletions (3 and 5 nt) were detected in the PRCV genome downstream of the S gene. The 3-nt deletion occurred in a noncoding region; however, the 5-nt deletion shortened the potential open reading frame A polypeptide from 72 to 53 amino acid residues. Significantly, a C-to-T substitution was detected in the last base position of the transcription recognition sequence upstream of open reading frame A, which rendered RNA 3 nondetectable in PRCV-infected cell cultures.",,"['Wesley, R D', 'Woods, R D', 'Cheung, A K']",,,,
,PMC,A domain at the 3' end of the polymerase gene is essential for encapsidation of coronavirus defective interfering RNAs.,,PMC240979,,,"Two murine hepatitis virus strain A59 defective interfering (DI) RNAs were generated by undiluted virus passages. The DI RNAs were encapsidated efficiently. The smallest DI particle, DI-a, contained a 5.5-kb RNA consisting of the following three noncontiguous regions from the MHV-A59 genome, which were joined in frame: the 5'-terminal 3.9 kb, a 798-nucleotide fragment from the 3' end of the polymerase gene, and the 3'-terminal 805 nucleotides. A full-length cDNA clone of the DI-a genome was constructed and cloned downstream of the bacteriophage T7 promoter. Transcripts derived from this clone, pMIDI, were used for transfection of MHV-A59-infected cells and found to be amplified and packaged. Deletion analysis of pMIDI allowed us to identify a 650-nucleotide region derived from the 3' end of the second open reading frame of the polymerase gene that was required for efficient encapsidation.",,"['van der Most, R G', 'Bredenbeek, P J', 'Spaan, W J']",,,,
,PMC,Identification of polypeptides encoded in open reading frame 1b of the putative polymerase gene of the murine coronavirus mouse hepatitis virus A59.,,PMC240963,,,"The polypeptides encoded in open reading frame (ORF) 1b of the mouse hepatitis virus A59 putative polymerase gene of RNA 1 were identified in the products of in vitro translation of genome RNA. Two antisera directed against fusion proteins containing sequences encoded in portions of the 3'-terminal 2.0 kb of ORF 1b were used to immunoprecipitate p90, p74, p53, p44, and p32 polypeptides. These polypeptides were clearly different in electrophoretic mobility, antiserum reactivity, and partial protease digestion pattern from viral structural proteins and from polypeptides encoded in the 5' end of ORF 1a, previously identified by in vitro translation. The largest of these polypeptides had partial protease digestion patterns similar to those of polypeptides generated by in vitro translation of a synthetic mRNA derived from the 3' end of ORF 1b. The polypeptides encoded in ORF 1b accumulated more slowly during in vitro translation than polypeptides encoded in ORF 1a. This is consistent with the hypothesis that translation of gene A initiates at the 5' end of ORF 1a and that translation of ORF 1b occurs following a frameshift at the ORF 1a-ORF 1b junction. The use of in vitro translation of genome RNA and immunoprecipitation with antisera directed against various regions of the polypeptides encoded in gene A should make it possible to study synthesis and processing of the putative coronavirus polymerase.",,"['Denison, M R', 'Zoltick, P W', 'Leibowitz, J L', 'Pachuk, C J', 'Weiss, S R']",,,,
,PMC,Equine arteritis virus is not a togavirus but belongs to the coronaviruslike superfamily.,,PMC240924,,,"The nucleotide sequence of the genome of equine arteritis virus (EAV) was determined from a set of overlapping cDNA clones and was found to contain eight open reading frames (ORFs). ORFs 2 through 7 are expressed from six 3'-coterminal subgenomic mRNAs, which are transcribed from the 3'-terminal quarter of the viral genome. A number of these ORFs are predicted to encode structural EAV proteins. The organization and expression of the 3' part of the EAV genome are remarkably similar to those of coronaviruses and toroviruses. The 5'-terminal three-quarters of the genome contain the putative EAV polymerase gene, which also shares a number of features with the corresponding gene of corona- and toroviruses. The gene contains two large ORFs, ORF1a and ORF1b, with an overlap region of 19 nucleotides. The presence of a ""shifty"" heptanucleotide sequence in this region and a downstream RNA pseudoknot structure indicate that ORF1b is probably expressed by ribosomal frameshifting. The frameshift-directing potential of the ORF1a/ORF1b overlap region was demonstrated by using a reporter gene. Moreover, the predicted ORF1b product was found to contain four domains which have been identified in the same relative positions in coronavirus and torovirus ORF1b products. The sequences of the EAV and coronavirus ORF1a proteins were found to be much more diverged. The EAV ORF1a product contains a putative trypsinlike serine protease motif. Our data indicate that EAV, presently considered a togavirus, is evolutionarily related to viruses from the coronaviruslike superfamily.",,"['den Boon, J A', 'Snijder, E J', 'Chirnside, E D', 'de Vries, A A', 'Horzinek, M C', 'Spaan, W J']",,,,
,PMC,Parallel mechanisms in neuropathogenesis of enteric virus infections.,,PMC240889,,,,,"['Morrison, L A', 'Fields, B N']",,,,
,PMC,Murine adenovirus infection of SCID mice induces hepatic lesions that resemble human Reye syndrome.,,PMC51658,,,"Murine adenovirus type 1 (MAV-1) infection of CB-17 SCID mice (which are homozygous for the severe combined immunodeficiency mutation) induces hepatic histopathologic and ultrastructural features that are strikingly similar to human Reye syndrome. Gross pathologic examination of MAV-1-infected mice revealed only pale yellow liver tissue. Histopathologic studies of tissue from MAV-1-infected mice revealed diffuse hepatic injury manifested by microvesicular fatty degenerative changes of hepatocytes and electron microscopic evidence of focal mitochondrial swelling with disruption of cristae and depletion of glycogen. Serum aminotransferase activities increased markedly in the infected animals; however, plasma ammonia levels were not elevated at the times assayed. Although all mice infected with MAV-1 died, neutralizing anti-MAV-1 monoclonal antibodies provided a dose-dependent delay in the appearance of clinical disease and hepatic histopathologic findings. Other findings included rare viral inclusions with only minimal inflammation in spleen, adrenal, and liver of infected mice. Our findings indicate that MAV-1 infection of SCID mice may provide important insights into the pathogenesis of the hepatic lesions of Reye syndrome.",,"['Pirofski, L', 'Horwitz, M S', 'Scharff, M D', 'Factor, S M']",,,,
,PMC,Translational frameshifting in the Escherichia coli dnaX gene in vitro.,,PMC329457,,,"Production of the gamma subunit of Escherichia coli DNA polymerase III holoenzyme is dependent on a very efficient translational frameshif in the dnaX gene. I used an E. coli in vitro translation system to analyze the mechanism of this frameshifting event. In this system, gamma was produced almost to the same extent as the inframe translation product, tau, suggesting that efficient frameshifting was reproduced in vitro. Coupling with transcription was not necessary for frameshifting. Addition of purified tau or gamma had no effect on the frameshifting process suggesting the absence of direct feedback regulation. By use of mutant genes, a strong pausing site was identified at or very close to the frameshift site. This pausing was apparently caused by a potential stem-loop structure which was previously shown to enhance frameshifting. Thus, enhancement of frameshifting by this putative stem-loop seems to be mediated by the translation pausing at the frameshift site. Despite the apparent structural similarity of the dnaX frameshift site to that of the eukaryotic retroviral genes, dnaX mRNA synthesized in vitro failed to direct the production of gamma in eukaryotic translation systems. This suggests that frameshifting in the dnaX gene depends on components specific to the E. coli translation system.",,"Tsuchihashi, Z",,,,
,PMC,Induction of HLA-DR expression on thyroid follicular cells by cytomegalovirus infection in vitro. Evidence for a dual mechanism of induction.,,PMC1886009,,,"Cytomegalovirus (CMV) infection of primary cultures established from human thyroid nodular and normal (paranodular) tissues resulted in induction of human leukocyte antigen (HLA) DR expression on thyroid follicular cells (TFC), as detected by cell-surface immunofluorescence staining with monoclonal antibodies (MAb). Two distinct modalities of induction were observed. The first type occurred in cultures of normal tissue obtained from CMV-seropositive but not seronegative donors, was detected on 30% to 50% of the TFCs, even though the vast majority of these cells failed to show any morphologic or antigenic evidence of individual CMV infection, and was associated with production of gamma-interferon (gamma-IFN) in vitro. The induced molecules displayed the characteristic DR polypeptide profile on immunoprecipitation and electrophoretic analysis. These results demonstrate that CMV infection of normal thyroid cultures may induce DR expression on TFCs in the absence of pre-existing lymphoid infiltrates and suggest that the induction is the result of an in vitro response to CMV by previously sensitized immunocompetent cells present in these primary cultures. Such a response, associated with the release of gamma-IFN, would induce DR expression on neighboring uninfected cells. The second mode of induction occurred in all CMV-infected cultures, regardless of their tissue origin (nodular or normal) or the serologic status of the donors. Up to 50% of infected TFCs at a late stage of infection, having fully developed CMV antigen-positive intranuclear inclusions, also displayed the cell-surface DR-related determinant recognized by one of the four anti-DR MAbs used. This induction was restricted to TFCs, while CMV-infected fibroblastoid cells present in the monolayers were invariably negative. Induction by CMV of major histocompatibility class II antigens on human epithelial cells may have significant implications in the development of normal immune responses against local viral infection, the enhancement of alloimmune rejection of grafted organs, and the generation of organ-specific autoimmune responses.",,"['Khoury, E. L.', 'Pereira, L.', 'Greenspan, F. S.']",,,,
,PMC,Enzyme immunohistochemical staining of formalin-fixed tissues for diagnosis in veterinary pathology,,PMC1481497,,,"Disease diagnosis often relies on the detection of specific antigens in tissue specimens. Enzyme-based immunohistochemical stains of formalin-fixed, paraffin-embedded tissues may be used to identify antigens associated with viral, bacterial and protozoal microorganisms, autoimmunity, and neoplasia. The detection of antigens in routinely fixed tissues offers several advantages over other diagnostic techniques. Sample submission is convenient and facilitates safe handling of potential human pathogens. Retrospective studies of stored specimens are possible. The technique is relatively rapid and enables detection of nonviable microorganisms. In addition, the ability to detect antigens in fixed specimens allows simultaneous visualization of the antigen and the histological lesion which may enhance the accuracy of diagnosis.",,"['Haines, Deborah M.', 'Clark, Edward G.']",,,,
,PMC,Ontario. Proliferative and necrotizing pneumonia (PNP) of swine: the Ontario situation,,PMC1481486,,,,,"['Thomson, Gary', 'Carman, Suzanne']",,,,
,PMC,Analysis of serotypes and electropherotypes of equine rotaviruses isolated in the United States.,,PMC269902,,,"Equine group A rotaviruses isolated over a 10-year period in New York State, New Jersey, Kentucky, and Texas were compared serotypically and electropherotypically. All isolates were determined to be serotype 3 by reaction with hyperimmune antiserum to the serotype 3 H-2 strain of equine rotavirus. All displayed RNA electrophoretic migration patterns related to that of the H-2 strain but distinct from that of serotype 5 strain H-1. A serologic survey of 184 mares in Kentucky, which was done to determine the incidence of H-1 and H-2 infections, showed geometric mean serum neutralizing titers to the H-2 strain of equine rotavirus to be significantly higher than those to the H-1 strain. These data suggest that the serotype 3 H-2 strain is the dominant equine rotavirus in Kentucky and perhaps elsewhere in the United States. We were unable to produce confirmational evidence that the H-1 strain occurs as a natural infection in the United States.",,"['Hardy, M E', 'Woode, G N', 'Xu, Z C', 'Williams, J D', 'Conner, M E', 'Dwyer, R M', 'Powell, D G']",,,,
,PMC,Assembly of empty capsids by using baculovirus recombinants expressing human parvovirus B19 structural proteins.,,PMC240632,,,"Empty parvovirus B19 capsids were isolated from insect cells infected with a recombinant baculovirus expressing parvovirus B19 VP2 alone and also with a double-recombinant baculovirus expressing both VP1 and VP2. That VP2 alone can assemble to form capsids is a phenomenon not previously observed in parvoviruses. The stoichiometry of the capsids containing both VP1 and VP2 was similar to that previously observed in parvovirus B19-infected cells. The capsids were similar to native capsids in size and appearance, and their antigenicity was demonstrated by immunoprecipitation and enzyme-linked immunosorbent assay with B19-specific antibodies.",,"['Brown, C S', 'Van Lent, J W', 'Vlak, J M', 'Spaan, W J']",,,,
,PMC,Age-dependent resistance to murine retrovirus-induced spongiform neurodegeneration results from central nervous system-specific restriction of virus replication.,,PMC240610,,,"The murine retrovirus CasBrE causes a noninflammatory spongiform degeneration of the central nervous system (CNS). Mice inoculated as neonates develop viremia and are susceptible to disease. However, mice inoculated at 10 days of age do not develop viremia and are totally resistant to the neurologic disease. We recently described a highly neurovirulent chimeric virus, FrCasE (J. L. Portis, S. Czub, C. F. Garon, and F. J. McAtee, J. Virol. 64:1648-1656, 1990), which contains the env gene of CasBrE. Mice inoculated at 10 days of age with this virus developed a viremia comparable to that in neonatally inoculated mice but, surprisingly, were still completely resistant to the neurodegenerative disease. A comparison of the tissue distribution of virus replication for mice inoculated at 1 or 10 days of age was determined by Southern blot analysis for the quantification of viral DNA and by infectious-center assay for the quantification of virus-producing cells. The levels of virus replication in the spleens were comparable in the two groups. In contrast, virus replication in the CNS of the resistant 10-day-old mice was markedly restricted (100- to 1,000-fold). Intracerebral inoculation did not overcome this restriction. A similar pattern of CNS-specific restriction of virus replication and resistance to disease was observed in athymic NIH Swiss nude mice inoculated at 10 days of age, suggesting that T-cell immunity was not involved. From our results, we conclude that the age-dependent resistance to disease is a consequence of the restriction of virus replication within the CNS due to the developmental state of the organ.",,"['Czub, M', 'Czub, S', 'McAtee, F J', 'Portis, J L']",,,,
,PMC,Nonsense codons within the Rous sarcoma virus gag gene decrease the stability of unspliced viral RNA.,,PMC360049,,,"The intracellular accumulation of the unspliced RNA of Rous sarcoma virus was decreased when translation was prematurely terminated by the introduction of nonsense codons within its 5' proximal gene, the gag gene. In contrast, the levels of spliced viral RNAs were not affected in our transient expression assays in chicken cells. Experiments using the transcription inhibitor dactinomycin showed that mutant unspliced RNAs were degraded more rapidly than wild-type RNA. Furthermore, mutant RNAs could be partially stabilized by coexpression of wild-type gag proteins in trans; however, intact gag proteins were not required to maintain the stability of RNAs which did not contain premature termination codons. Thus, termination codons seemed to destabilize the RNA not because of their effect on gag protein function but instead because they disrupted the process of translating the gag region of the RNA. Analysis of double-mutant constructs containing both deletions and termination codons within the gag gene also suggested that the stability of the unspliced RNA was affected by a cis-acting interaction between the RNA and ribosomes.",,"['Barker, G F', 'Beemon, K']",,,,
,PMC,"Antiviral activity against transmissible gastroenteritis virus, and cytotoxicity, of natural porcine interferons alpha and beta.",,PMC1263434,,,"Porcine interferon (POIFN)-alpha prepared in primed peripheral blood leukocyte cultures induced with Newcastle disease virus and POIFN-beta from PK-15 cell cultures induced with polyinosinic:polycytidylic acid were partially purified by precipitation with potassium thiocyanate and anion exchange chromatography. Mean purification factors in terms of units of POIFN per mg of protein, of 37 and 12 were obtained for POIFN-alpha and POIFN-beta respectively. In yield reduction assays in swine testis and pig kidney cell cultures, POIFN-alpha and POIFN-beta had greater antiviral activity against vesicular stomatitis virus than against transmissible gastroenteritis virus (TGEV). The antiviral effects were greater at higher concentrations of interferon (IFN), and when the IFN treatments were continued postinfection. Porcine interferon-beta showed greater antiviral activity against TGEV than POIFN-alpha, but this may have been partly due to cytotoxicity. There were no major differences in the antiviral activities of crude and partially purified IFN preparations. Both types of IFN showed antiviral activity against TGEV in yield reduction assays in porcine intestinal explant and intestinal epithelial cell cultures. Crude POIFN-beta was found to be rapidly cytotoxic, especially in porcine cells, and some fractions of partially purified POIFN-beta were also cytotoxic. The cytotoxicity of POIFN-beta was partially neutralized by antibodies against human IFN-beta, but human IFN-beta was not cytotoxic for porcine or bovine cells.",,"['Weingartl, H M', 'Derbyshire, J B']",,,,
,PMC,Dissociation and reassociation of oligomeric viral glycoprotein subunits in the endoplasmic reticulum.,,PMC240033,,,"The vesicular stomatitis virus (VSV) glycoprotein (G) forms noncovalently linked trimers in the endoplasmic reticulum (ER) prior to transport to the cell surface. Here we examined the formation of heterotrimers between wild-type and mutant subunits that were retained in the ER by C-terminal retention signals. When G protein was coexpressed with mutant subunits that formed trimers at the wild-type rate and were transported from the ER at the wild-type rate, heterotrimers were readily detected. In contrast, when G protein was coexpressed with mutant subunits that formed trimers at the wild-type rate, but were retained in the ER, heterotrimers were not detected unless transport of the wild-type molecules from the ER was blocked. After removal of transport block, the heterotrimers then dissociated and reassorted to homotrimers of the mutant protein that were retained in the ER and wild-type trimers that were transported to the cell surface. These and other results presented here indicate that there is an equilibrium between G protein trimers and monomers in vivo, at least in the ER. This equilibrium may function to allow escape of wild-type subunits from aberrant retained subunits.",,"['Zagouras, P', 'Ruusala, A', 'Rose, J K']",,,,
,PMC,Direct evidence of a role for amino acid 101 of VP-1 in central nervous system disease in Theiler's murine encephalomyelitis virus infection.,,PMC240018,,,"The DA virus, a member of the TO subgroup of Theiler's virus, invokes a chronic demyelinating disease in its natural host, the mouse, RNA transcripts from a cDNA clone, pDAFL3, are infectious, and the resulting virus, DAFL3, produces in mice a disease indistinguishable from that caused by the DA virus. Using oligonucleotide-directed site-specific mutagenesis, a single nucleotide, cytosine at position 3305 (viral genome), was changed in this infectious cDNA to a thymine. The mutated nucleotide is located in an area coding for a neutralizing epitope on loop II of VP-1. Virus OSM101, produced from the mutagenized plasmid pDA101, had the same growth characteristics and plaque phenotype in vitro as the virus DAFL3 produced from clone pDAFL3. However, in vivo in the mouse, virus OSM101 was markedly less neurovirulent than DAFL3. Central nervous system tissues from mice infected 4 to 6 weeks previously with the OSM101 virus contained less infectious virus and fewer infected cells than central nervous system tissues from animals infected with the control virus, DAFL3. Thus, we demonstrated that the single nucleotide change resulting in an amino acid substitution at position 101 (threonine to isoleucine) of VP-1 determines one aspect of Theiler's virus persistence and disease in mice.",,"['Zurbriggen, A', 'Thomas, C', 'Yamada, M', 'Roos, R P', 'Fujinami, R S']",,,,
,PMC,Alteration of the pH dependence of coronavirus-induced cell fusion: effect of mutations in the spike glycoprotein.,,PMC240014,,,"Infection of susceptible murine cells with the coronavirus mouse hepatitis virus type 4 (MHV4) results in extensive cell-cell fusion at pHs from 5.5 to 8.5. The endosomotropic weak bases chloroquine and ammonium chloride do not prevent MHV4 infection. In marked contrast, we have selected variants from a neural cell line persistently infected with MHV4 which are entirely dependent on acid pH to fuse host cells and are strongly inhibited by endosomotropic weak bases. Wild-type and variant viruses were compared at the level of the fusion-active surface (S) glycoprotein gene. Cloning and sequencing of each 4,131-base open reading frame predicted a total of eight amino acid differences which fell into three distinct clusters. Each S glycoprotein, when expressed from cDNA, was synthesized in equivalent amounts, and similar proportions were transported to the cell surface. Wild-type S induced cell-cell fusion at neutral pH, whereas variant S required prolonged exposure to acidic pH to induce fusion. Expression of hybrid S genes prepared by exchange of restriction fragments between wild-type and variant cDNAs revealed that elimination of neutral pH fusion was solely dependent on amino acid alterations at positions 1067 (Q to H), 1094 (Q to H), and 1114 (L to R). These changes lie within a predicted heptad repeat region of the transmembrane cleavage fragment of S (S2). These findings demonstrate that the pH dependence of coronavirus fusion is highly variable and that this variability can be determined by as few as three amino acid residues.",,"['Gallagher, T M', 'Escarmis, C', 'Buchmeier, M J']",,,,
,PMC,Induction of self-reactive T cells after murine coronavirus infection.,,PMC239986,,,"We studied the mechanism of in vitro spontaneous lymphokine production by spleen cells from mice injected intraperitoneally with murine coronavirus stain JHM 1 month after infection, when infectious virus had already been cleared from the spleens. Removal of either CD4+ T cells or Ia+ antigen-presenting cells (APC) from the spleen cells abrogated interleukin-2 (IL-2) production. Addition of anti-CD4 or anti-Iad monoclonal antibodies to the culture suppressed IL-2 production. These results suggest that the response involved typical receptor-mediated activation of T cells. Surprisingly, reciprocal mixing experiments with a coculture of T cells from infected mice and APC from either infected or naive mice resulted in the production of IL-2. The absence of viral antigens in spleen cells 1 month after infection, as indicated by their inability to induce the proliferation of T-cell clones specific for the viral antigens, suggest that the T cells from mice 1 month after infection were not responding to the viral antigens. The inoculum components other than the virus did not induce this immune response. We also found that the frequency of self-reactive but not alloreactive IL-2-producing T cells in the spleens of infected mice was 3- to 10-fold higher than that in naive mice. These findings suggest that an increased frequency of self-reactive T cells which secrete IL-2 occurs following murine coronavirus infection. This may have important implications in the development of autoimmunelike phenomena following murine coronavirus infection.",,"['Kyuwa, S', 'Yamaguchi, K', 'Toyoda, Y', 'Fujiwara, K']",,,,
,PMC,Measles virus nucleocapsid protein protects rats from encephalitis.,,PMC239973,,,"Lewis rats immunized with recombinant vaccinia virus expressing the nucleocapsid (N) protein of measles virus were protected from encephalitis when subsequently challenged by intracerebral infection with neurotropic measles virus. Immunized rats revealed polyvalent antibodies to the N protein of measles virus in the absence of any neutralizing antibodies as well as an N protein-specific proliferative lymphocyte response. Depletion of CD8+ T lymphocytes did not abrogate the protective potential of the N protein-specific cell-mediated immune response in rats, while protection could be adoptively transferred with N protein-specific CD4+ T lymphocytes. These results indicate that a CD4+ cell-mediated immune response specific for the N protein of measles virus is sufficient to control measles virus infections of the central nervous system.",,"['Bankamp, B', 'Brinckmann, U G', 'Reich, A', 'Niewiesk, S', 'ter Meulen, V', 'Liebert, U G']",,,,
,PMC,The role of management and the use of vaccines in the control of acute undifferentiated diarrhea of newborn calves,,PMC1480970,,,,,"Radostits, Otto M.",,,,
,PMC,Localization of immunogenic regions on the flagellin proteins of Campylobacter jejuni 81116.,,PMC258373,,,"The purpose of this study was to localize antigenic regions on the flagellin protein of Campylobacter jejuni 81116. This strain has two flagellin genes, flaA and flaB, which are 95% identical; only flaA seems to be expressed in motile C. jejuni 81116 cells. Fragments of flaA and flaB were cloned in the bacterial expression vector pEX, and the expression products were incubated with flagellin-specific antibodies. Monoclonal antibodies to broadly cross-reactive epitopes recognized fragments that are located in the termini (CF16 and CF17) and in the center (CF15) of both flagellin A and B proteins. Most of the serotype-specific monoclonal antibodies (CF1, CF2, CD3, CF4, and CF13) reacted with only the center of flagellin A in an area where flagellin A and B differ in 6 amino acid residues. The epitopes in this area were further characterized by competitive binding experiments. The charge and molecular weight microheterogeneity of flagellin, as determined by two-dimensional gel electrophoresis, were unrelated to the expression of both flagellin genes or parts thereof.",,"['Nuijten, P J', 'van der Zeijst, B A', 'Newell, D G']",,,,
,PMC,Mouse hepatitis virus strain UAB infection enhances resistance to Salmonella typhimurium in mice by inducing suppression of bacterial growth.,,PMC258337,,,"We have previously shown that intranasal infection of mice with mouse hepatitis virus (MHV) strain UAB (MHV-UAB) increases their resistance to Salmonella typhimurium injected intravenously 6 days later. To study how salmonella resistance was induced, BALB/cAnNCr mice were infected with salmonella strains carrying specific genetic alterations. One set of studies compared the effect of MHV infection on subsequent salmonella infections with AroA- (avirulent) and Aro+ (virulent) salmonellae. Unlike its effect on Aro+ salmonellae, MHV failed to reduce the number of AroA- salmonellae recovered from mice. Because AroA- S. typhimurium shows almost no growth in vivo, this failure indicated that the effect of MHV on salmonella resistance required growth of the infecting salmonellae. In other studies, the effect of MHV infection on both growth and killing were monitored simultaneously in mice with growing salmonellae carrying a single copy of the temperature-sensitive pHSG422 plasmid, which is unable to replicate in vivo. MHV infection reduced salmonella growth but caused no increase in salmonella killing. MHV infection of mice given wild-type salmonellae also resulted in no increase in salmonella killing 4 h after salmonella challenge. These studies demonstrate that MHV-UAB infection increases host resistance to salmonellae by enhancing suppression of bacterial growth instead of by increasing the amount of salmonella killing.",,"['Fallon, M T', 'Benjamin, W H', 'Schoeb, T R', 'Briles, D E']",,,,
,PMC,"Experimental infection of newborn pigs with an attaching and effacing Escherichia coli O45:K""E65"" strain.",,PMC258332,,,"The ability of a nonenterotoxigenic, K88-negative porcine Escherichia coli strain of serogroup O45:K""E65"" to induce attaching-effacing lesions was investigated in newborn pigs. Typical attaching-effacing lesions, characterized by intimate adherence of bacteria to mature enterocyte brush borders with effacement of the microvilli, were observed on light and electron microscopy. Bacteria were also seen in intracytoplasmic vacuoles of mature enterocytes and, in areas of heavier colonization, in the lamina propria of the intestinal mucosa. A moderate inflammatory response with mild focal ulceration of the intestinal mucosa was observed. In a sequential study, we observed that the attaching-effacing lesions were well established in the duodenum, jejunum, and ileum at 12 h postinoculation but did not develop in the cecum and colon until 24 to 48 h postinoculation, although bacteria had colonized the latter areas as early as 12 h postinoculation. Initially, bacteria were very intimately attached, with an irregular arrangement on the enterocyte apical cell membrane, and subsequently reoriented to form a typical palisade arrangement with a narrow regular gap between the bacterial cell wall and the enterocyte apical cell membrane. This phenomenon of early intimate attachment of irregularly disposed bacteria has not been reported for human enteropathogenic attaching and effacing E. coli and could represent a new and different mechanism of attachment and effacement to intestinal epithelial cells.",,"['Helie, P', 'Morin, M', 'Jacques, M', 'Fairbrother, J M']",,,,
,PMC,Mycoplasma pulmonis infections cause long-lasting potentiation of neurogenic inflammation in the respiratory tract of the rat.,,PMC329866,,,"These experiments were done to learn whether Mycoplasma pulmonis infections of the respiratory tract of rats can potentiate ""neurogenic inflammation"" and whether this potentiation is amplified by factors that exacerbate the infections. Pathogen-free F344 rats were inoculated intranasally with M. pulmonis or with sterile culture medium and then lived for 4 wk in an ammonia-free atmosphere or in air containing ammonia (100 parts per million). Neurogenic inflammation was evoked by an intravenous injection of capsaicin, and 5 min later the magnitude of the response was quantified by measuring the amount of extravasation of two tracers, Monastral blue pigment and Evans blue dye. We found that vascular permeability in the tracheas of all rats was normal in the absence of capsaicin. However, a 75-micrograms/kg dose of capsaicin, which caused almost no extravasation of Evans blue in the tracheas of pathogen-free controls (17 +/- 3 ng/mg; mean +/- SE), produced extensive extravasation in the infected rats (135 +/- 18 ng/mg; P less than 0.001). Similarly, this dose of capsaicin produced 30 times as much Monastral blue extravasation in the infected rats (area density = 47 +/- 8% of surface area) as it did in the pathogen-free rats (1.6 +/- 0.5%; P less than 0.001), a difference that resulted from increases in the number of Monastral blue-labeled postcapillary venules and in the amount of labeling per venule. Exposure of the infected rats to ammonia exacerbated the infections, further increased the number of Monastral blue-labeled vessels and the amount of labeling per vessel, and made the rats so sensitive to capsaicin that a normally tolerable dose of 150 micrograms/kg i.v. caused fatal apnea. Ammonia did not have these effects in pathogen-free rats. We conclude that M. pulmonis infections of the airway mucosa cause a potent, long-lasting potentiation of neurogenic inflammation, which results in part from an increase in the number and responsiveness of mediator-sensitive postcapillary venules. These changes can be amplified by environmental factors such as ammonia which exacerbate the infections.",,"['McDonald, D M', 'Schoeb, T R', 'Lindsey, J R']",,,,
,PMC,"Outbreak of human calicivirus gastroenteritis in a day-care center in Sydney, Australia.",,PMC269815,,,"Between January and March 1988, an outbreak of gastroenteritis occurred among children and staff at a day-care center in Sydney, New South Wales, Australia. Over an 11-week period, 53 persons had 101 episodes of gastroenteritis; some patients had 5 separate episodes. The principal etiologic agent in the outbreak, human calicivirus (HCV), was detected by electron microscopy in 32% of fecal specimens from children and staff members with symptoms but in only 8% of asymptomatic individuals (P less than 0.01). HCV was confirmed by both an enzyme immunoassay and solid-phase immune electron microscopy. HCV infection was a particular problem in infants, who had the highest age-specific attack rates, had the greatest symptomatic/asymptomatic infection ratio, and were most likely to have a second symptomatic episode. The mode of transmission of this virus was not identified, and extensive efforts to control the 11-week outbreak had little effect. Prolonged excretion of HCV by some symptomatic patients and high rates of asymptomatic infection may have contributed to the extended duration of the outbreak. HCV may be a common cause of gastroenteritis in children that is under-recognized because of insensitive methods of detection.",,"['Grohmann, G', 'Glass, R I', 'Gold, J', 'James, M', 'Edwards, P', 'Borg, T', 'Stine, S E', 'Goldsmith, C', 'Monroe, S S']",,,,
,PMC,cDNA probes for the diagnosis of bovine torovirus (Breda virus) infection.,,PMC269807,,,"A genomic cDNA library of RNA from Breda virus (BRV), a bovine torovirus, was prepared. The nucleotide sequence of the 3' end of the genome was found to be highly conserved (93% identical) between BRV and Berne virus, the torovirus prototype. Cross-hybridization experiments were performed to select Berne virus cDNA clones for use as probes in a dot hybridization assay; the objective was to detect heterologous torovirus RNA in fecal material. A rapid RNA extraction method was employed to make the test applicable for routine diagnosis. Samples from calves after experimental and natural infection with BRV were assayed to establish the sensitivity and specificity of the test and to compare the test with the enzyme-linked immunosorbent assay (ELISA) for antigen detection. For this purpose, 53 samples from seven infected calves were tested with both methods. In the ELISA, BRV was detected in six fecal samples from three inoculated calves. By use of the hybridization test, 16 samples from seven calves reacted positively. With one exception, only postinoculation samples were found positive in hybridization. No signal was seen in feces from uninoculated calves or from calves infected with rotavirus or coronavirus.",,"['Koopmans, M', 'Snijder, E J', 'Horzinek, M C']",,,,
,PMC,Assembly and polarized release of Punta Toro virus and effects of brefeldin A.,,PMC239922,,,"Punta Toro virus (PTV), a member of the sandfly fever group of bunyaviruses, is assembled by budding at intracellular membranes of the Golgi complex. We have examined PTV glycoprotein transport, assembly, and release and the effects of brefeldin A (BFA) on these processes. Both the G1 and G2 proteins were transported out of the endoplasmic reticulum (ER) and retained in the Golgi complex in a stable structure, either during PTV infection or when expressed from a vaccinia virus recombinant. BFA treatment causes a rapid and dramatic change in the distribution of the G1 and G2 proteins, from a Golgi pattern to an ER pattern. The G1 and G2 proteins were found to be modified by medial but not trans Golgi network enzymes, in the presence or absence of BFA. We found that BFA blocks PTV release from cells but does not interfere with the intracellular assembly of infectious virions. Further, the BFA block of virus release is fully reversible, with high levels of virus release occurring upon removal of the inhibitor. It was also found that the release of PTV virions is polarized, occurring exclusively from the basolateral surfaces of the polarized Vero C1008 epithelial cell line.",,"['Chen, S Y', 'Matsuoka, Y', 'Compans, R W']",,,,
,PMC,Efficacy of halofuginone lactate against Cryptosporidium parvum in calves.,,PMC244992,,,"The efficacy of halofuginone lactate against natural Cryptosporidium parvum infection in 150 neonatal market calves of a mixed Belgian breed was tested. The drug was administered orally in the milk replacer over a period of 3 to 14 days at doses ranging from 30 to 500 micrograms/kg of body weight. Over a period of 4 weeks, the animals were examined twice a week for shedding of C. parvum oocysts and were scored semiquantitatively for diarrhea. Weight gain was assessed after 2 and 4 weeks. Subclinical infections by rota-, corona-, and bovine picobirnaviruses were equally distributed in the different groups. In total, 93% of the unmedicated calves eliminated C. parvum within 10 days after arrival at the rearing unit and 62% of them showed diarrhea. Immediately after treatment with halofuginone was started, no more signs of Cryptosporidium-associated diarrhea were established. From the level of 60 micrograms/kg on, oocysts were no longer detected in 98% of animals 5 to 6 days after the start of treatment. Animals remained negative for at least 7 days after withdrawal of the drug. From 7 to 10 days after withdrawal, some animals excreted oocysts again. The number of shedders was closely linked with increasing doses of the drug, which indicates that lower doses do not interrupt infection completely and allow development of immunity. In this respect, a dose of 60 to 125 micrograms/kg over a period of 7 days seems most appropriate in practice. Toxic side effects were noticed only at 500 micrograms/kg.",,"['Villacorta, I', 'Peeters, J E', 'Vanopdenbosch, E', 'Ares-Mazás, E', 'Theys, H']",,,,
,PMC,Restricted virus replication in the spinal cords of nude mice infected with a Theiler's virus variant.,,PMC239852,,,"The Daniels strain of Theiler's murine encephalomyelitis produces a chronic disease which is an animal model for human demyelinating disorders. Previously, we selected a neutralization-resistant virus variant producing an altered and diminished central nervous system disease in immunocompetent mice which was evident during the later stage of infection (after 4 weeks) (A. Zurbriggen and R. S. Fujinami, J. Virol. 63:1505-1513, 1989). The exact epitope determining neurovirulence was precisely mapped to a capsid protein, VP-1, and represents a neutralizing region (A. Zurbriggen, J. M. Hogle, and R. S. Fujinami, J. Exp. Med. 170:2037-2049, 1989). Here, we present experiments with immunoincompetent animals to determine viral replication, spread, and targeting to the central nervous system in the absence of detectable antibodies or functional T cells. Nude mice were infected orally, and the virus was monitored by plaque assay, immunohistochemistry, and in situ hybridization. Early during the infection (1 week), the variant virus induced an acute disease comparable to that induced by the wild-type virus in these nude mice. Alterations in tropism in the central nervous system were not apparent when wild-type parental Daniels strain virus was compared with the variant virus. Moreover, variant virus replicated in tissue culture (BHK-21 cells) to similarly high titers in a time course identical to that of the wild-type virus (A. Zurbriggen and R. S. Fujinami, J. Virol. 63:1505-1513, 1989). However, replication of the variant virus versus the wild-type virus within the spinal cord of athymic nude mice infected per os was substantially restricted by 6 weeks postinfection. Therefore, the reduced neurovirulence in the later stage (6 weeks) of the disease is most likely due to a diminished growth rate or spread of the variant virus in the central nervous system rather than to marked differences in viral tropism.",,"['Zurbriggen, A', 'Yamada, M', 'Thomas, C', 'Fujinami, R S']",,,,
,PMC,An RNA hairpin at the extreme 5' end of the poliovirus RNA genome modulates viral translation in human cells.,,PMC239832,,,"Several mutations were introduced into an infectious poliovirus cDNA clone by inserting different oligodeoxynucleotide linkers into preexisting DNA restriction endonuclease sites in the viral cDNA. Ten mutated DNAs were constructed whose lesions mapped in the 5' noncoding region or in the capsid coding region of the viral genome. Eight of these mutated cDNAs did not give rise to infectious virus upon transfection into human cells, one yielded virus with a wild-type phenotype, and one gave rise to a viral mutant with a small-plaque phenotype. This last mutant, designated 1-5NC-S21, bears a 6-nucleotide insertion in the loop of a stable RNA hairpin at the very 5' end of the viral genome. Detailed analysis of the biological properties of 1-5NC-S21 showed that the primary defect in mutant-infected cells is a fivefold decrease in translation relative to wild-type-infected cells. Transfection into HeLa cells of in vitro-synthesized RNA molecules bearing either the 5' noncoding region of 1-5NC-S21 or wild-type poliovirus upstream of a luciferase reporter gene showed that the mutated RNA hairpin was responsible for the observed decrease in viral translation in mutant-infected cells and conferred this defect to heterologous RNAs. These findings indicate that an RNA hairpin located at the extreme 5' end of the viral RNA and highly conserved among enteroviruses and rhinoviruses profoundly affects the translation efficiency of poliovirus RNA in infected cells.",,"['Simoes, E A', 'Sarnow, P']",,,,
,PMC,New nucleotide sequence data on the EMBL File Server.,,PMC333621,,,,,,,,,
,PMC,Recurrent wheezy bronchitis and viral respiratory infections.,,PMC1793220,,,"Fifty four patients aged from 1 to 6 years who had had recurrent attacks of wheezy bronchitis were prospectively followed up for three months to find out if there was an association between different viral respiratory infections and episodes of wheezing. Of the 115 episodes of upper or lower respiratory tract symptoms, virus or Mycoplasma pneumoniae infection were diagnosed in 52 (45%). Thirty four of rhinoviruses. The patients had an average of 2.1 episodes of respiratory tract symptoms the total mean (SD) duration of which was 30 (2) days of the 92 days that followed. Wheezing occurred during 76 (66%) of the 115 episodes and during a third of these the patient was admitted to hospital because of severe dyspnoea. Wheezing started a mean (SD) of 43 (7) hours after the first symptoms of respiratory infection and persisted for 3.8 (4.2) days in patients in whom virus infection was diagnosed. The incidence of wheezing was not associated with IgE mediated atopy, with positive virological tests, or with fever during virus infection, but was associated with parental smoking and more than one sibling.",,"['Mertsola, J', 'Ziegler, T', 'Ruuskanen, O', 'Vanto, T', 'Koivikko, A', 'Halonen, P']",,,,
,PMC,Experimental sialodacryoadenitis virus infection in severe combined immunodeficient mice.,,PMC1263420,,,"Mice with a severe combined immunodeficiency in B and T lymphocytes and natural killer cells (SCID-beige) were inoculated intranasally with sialodacryoadenitis (SDA) virus, a coronavirus of rats. Animals were killed at designated intervals and tissues were examined for evidence of viral infection by light microscopy and immunofluorescence microscopy. Based on these criteria, there was no evidence that these immunodeficient mice were susceptible to infection with SDA virus.",,"['Percy, D H', 'Williams, K L', 'Croy, B A']",,,,
,PMC,"Jejunal mucosal lactase activity from birth to three weeks in conventionally raised calves fed an electrolyte solution on days 5, 6 and 7 instead of milk.",,PMC1263419,,,"The purpose of this study was to evaluate the effect of withdrawal of lactose from the diet for 72 hours on lactase activity in the jejunal mucosa of conventionally raised calves. The descending portion of the duodenum of six Holstein calves less than 24 hours old was cannulated. The calves were fed milk except on days 5, 6 and 7 when they were given the same volume of an electrolyte solution. Sequential biopsy specimens of the proximal jejunal mucosa were obtained for three weeks and the lactase activity determined. Lactase activity was highest on day 1 and a trend toward decreased lactase activity from birth until three weeks was observed. Mean lactase activity was significantly (p less than 0.05) higher for days 1, and 3 compared to days 9, 13 and 17. The withdrawal of milk and replacement by an electrolyte solution during three days had no significant effect on jejunal mucosal lactase activity in neonatal calves.",,"['St Jean, G D', 'Schmall, L M', 'Rings, D M', 'Hoffsis, G F', 'Hull, B L']",,,,
,PMC,Coronavirus infection in the laboratory rat: immunization trials using attenuated virus replicated in L-2 cells.,,PMC1263415,,,"Sixty-nine specific pathogen-free male Wistar rats approximately eight weeks of age were used to evaluate the efficacy of an attentuated strain of sialodacryoadenitis (SDA) virus in providing protection against infection on subsequent challenge with virulent SDA virus. Fifty-four animals were inoculated intranasally with approximately 10(3.5) median cell culture infectious doses of the 25th passage of SDA virus in L-2 cells. Randomly-selected vaccinated animals were killed in order to evaluate the safety and efficacy of attenuated virus by histopathological examination of the salivary glands, lacrimal glands, and lower respiratory tract, and titration of sera for antibody to SDA virus. At three months and six months postvaccination (pv), animals were selected at random and challenged with virulent SDA virus. Seronegative, age-matched animals were also challenged, and served as controls. In animals examined at six to ten days pv, lesions were absent in submandibular and parotid salivary glands and lacrimal glands, but transient lesions were present in major airways of the lower respiratory tract. In a comparison of the incidence and extent of lesions, and antibody titers in challenged vaccinates and seronegative controls, lesions were minimal or absent in vaccinates compared to challenged naive rats, particularly in animals inoculated at three months pv. In addition, antibody titers in challenged vaccinates were much higher than were postinoculation titers in inoculated controls. In a comparison of lesions in salivary and lacrimal glands in vaccinated and control animals challenged at six months pv, there was a significant reduction in the number of animals without lesions in the vaccinated group (p = less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)",,"['Percy, D H', 'Scott, R A']",,,,
,PMC,Sensitivity and specificity of an enzyme-linked immunosorbent assay for the detection of bovine viral diarrhea virus antibody in cattle.,,PMC1263414,,,"A reliable bovine viral diarrhea (BVD) viral antigen was prepared from BVD virus grown on Madin Darby bovine kidney (MDBK) cells by solubilizing the virus with detergent MEGA-10 (decanoyl-N-methylglucamide) followed by removal of hydrophobic proteins with Triton X-100 treatment. By these treatments, problems of high background associated with BVD viral antigen in the enzyme-linked immunosorbent assay (ELISA) were eliminated. With this new antigen, an ELISA was adapted to detect bovine serum antibody against BVD virus. The diagnostic specificity of the assay in 403 bovine sera collected from a BVD virus-free herd was 100%; in 296 bovine sera with serum neutralizing antibody titers of greater than or equal to 1:2, 289 sera were ELISA positive (relative sensitivity of 97.6%), two sera gave false negative reactions (0.7%) and five sera gave suspicious reactions (1.7%). These interpretations were based on positive/negative (P/N) ratio readings, i.e. a P/N ratio of less than 1.50, 1.50-1.99 and greater than or equal to 2.00 were interpreted as negative, suspicious and positive reactions, respectively. The ELISA results gave excellent agreement with serum neutralization in detecting both seropositive and seronegative animals (Kappa = 0.994). The ELISA assay was considered to be technically superior to the serum neutralization test for the routine detection of BVD viral antibody in bovine sera.",,"['Cho, H J', 'Masri, S A', 'Deregt, D', 'Yeo, S G', 'Thomas, E J']",,,,
,PMC,MHC class II-restricted T-cell hybridomas recognizing the nucleocapsid protein of avian coronavirus IBV.,,PMC1384328,,,"Mice were immunized with purified infectious bronchitis virus (IBV), strain M41. Spleen cells, expanded in vitro by stimulation with M41, were immortalized by fusion to obtain T-cell hybridomas, and two major histocompatability complex (MHC) class II (I-E)-restricted T-cell hybridomas were selected with specificity for IBV. Both hybridomas selectively recognized the internal nucleocapsid protein. The responses to 12 different strains of IBV varied markedly. This demonstrates antigenic variation of the nucleocapsid protein in addition to the known variation of the surface glycoprotein S.",,"['Boots, A M', 'Van Lierop, M J', 'Kusters, J G', 'Van Kooten, P J', 'Van der Zeijst, B A', 'Hensen, E J']",,,,
,PMC,Differentiation of transmissible gastroenteritis virus from porcine respiratory coronavirus and other antigenically related coronaviruses by using cDNA probes specific for the 5' region of the S glycoprotein gene.,,PMC269734,,,"Two cDNA clones prepared from the virulent Miller strain of transmissible gastroenteritis virus (TGEV) were identified, and their nucleotide sequences were determined. The clones were nonoverlapping and located in the 5' region of the S glycoprotein gene. Their nucleotide and predicted amino acid sequences were compared with published sequences of the attenuated Purdue strain of TGEV and feline infectious peritonitis virus (FIPV). TGEV clone pE21 contained 381 bp of the S glycoprotein gene and had greater than 98% nucleotide and amino acid sequence homology with Purdue TGEV and over 87% nucleotide and amino acid sequence homology with FIPV. TGEV clone pD24 contained 267 bp of the S glycoprotein gene. It had greater than 98% nucleotide and amino acid sequence homology with Purdue TGEV but only 54% nucleotide sequence homology and 24% amino acid sequence homology with FIPV. A probe prepared from pD24 could differentiate TGEV from porcine respiratory coronavirus and other antigenically related coronaviruses, FIPV, feline enteric coronavirus, and canine coronavirus in a dot blot hybridization assay.",,"['Bae, I', 'Jackwood, D J', 'Benfield, D A', 'Saif, L J', 'Wesley, R D', 'Hill, H']",,,,
,PMC,Minus-strand copies of replicating coronavirus mRNAs contain antileaders.,,PMC240520,,,"The 5' leader sequence on mRNAs of the porcine transmissible gastroenteritis coronavirus was determined and found to be 90 nucleotides in length. An oligodeoxynucleotide with a sequence from within the leader was used as a probe in Northern analysis on RNA from infected cells, and an antileader (a minus-strand copy of the leader sequence) was shown to be present on all mRNA minus-strand species. RNase protection analysis showed the antileader to be approximately the same length as the leader. The kinetics of antileader appearance was the same as that for the appearance of minus-strand RNA species. This, along with a demonstration that viral mRNAs become packaged, gives further support to the idea that coronavirus mRNAs can undergo replication via subgenomic mRNA-length replicative intermediates, and that input mRNAs from infecting virions may serve as initial templates for their own replication. In this sense, then, coronaviruses behave in part like RNA viruses with segmented genomes.",,"['Sethna, P B', 'Hofmann, M A', 'Brian, D A']",,,,
,PMC,Expression of bovine herpesvirus 1 glycoprotein gIV by recombinant baculovirus and analysis of its immunogenic properties.,,PMC240513,,,"The gene encoding the gIV glycoprotein of bovine herpesvirus 1 has been inserted into the genome of Autographa californica baculovirus in lieu of the coding region of the A. californica baculovirus polyhedrin gene. Recombinant protein was identified by its reactivity with gIV-specific monoclonal antibodies and expressed at high levels (about 85 micrograms per 2.5 x 10(6) cells) in Spodoptera frugiperda (SF9) cells. The recombinant glycoprotein had an apparent molecular mass of 63 kDa, indicating that it was incompletely glycosylated. However, it was transported to and expressed on the cell surface of infected SF9 cells. Furthermore, reactivity with polyclonal and monoclonal antibodies specific for gIV suggested that most epitopes were functionally unaltered on the recombinant gIV. Immunization of cattle with recombinant gIV in crude, partially purified, or pure form resulted in the induction of neutralizing antibodies to BHV-1, which were reactive with authentic gIV. However, the neutralizing antibody titers were lower than those elicited by an equivalent amount of affinity-purified authentic gIV, which appeared to be mainly due to reduced recognition of one of the neutralizing antigenic domains of gIV, designated domain I. The potential use of this recombinant gIV glycoprotein as a vaccine to bovine herpesvirus 1 infection in cattle is discussed.",,"['van Drunen Littel-van den Hurk, S', 'Parker, M D', 'Fitzpatrick, D R', 'Zamb, T J', 'van den Hurk, J V', 'Campos, M', 'Harland, R', 'Babiuk, L A']",,,,
,PMC,Analysis of murine coronavirus surface glycoprotein functions by using monoclonal antibodies.,,PMC240512,,,"The murine coronavirus surface glycoprotein gene was expressed as a fusion protein in bacteria, and the expressed protein was used to generate S protein-specific monoclonal antibodies (MAbs). Three of the MAbs, 11F, 30B, and 10G, were able to neutralize virus infectivity, and two of them, 11F and 10G, were able to block virus-induced, cell-to-cell fusion. The binding sites of the 11F, 30B, and 10G MAbs were determined by Western immunoblotting and epitope mapping. The 11F and 30B MAbs bound to sites located, respectively, between amino acids 33 to 40 and 395 to 406 in the amino-terminal (S1) subunit of the S protein, and the 10G MAb bound to a site located between amino acids 1123 and 1137 in the carboxy-terminal (S2) subunit. These data define more precisely the interactions between the S1 and S2 subunits of the murine coronavirus S protein and provide further insights into its structure and function.",,"['Routledge, E', 'Stauber, R', 'Pfleiderer, M', 'Siddell, S G']",,,,
,PMC,Internally located cleavable signal sequences direct the formation of Semliki Forest virus membrane proteins from a polyprotein precursor.,,PMC240499,,,"The proteolytic processes involved in the cotranslational production of the Semliki Forest virus proteins p62, 6K, and E1 from a common precursor polypeptide were analyzed by an in vitro translation-translocation assay. By studying the behavior of wild-type and mutant variants of the polyprotein, we show that the signal sequences responsible for membrane translocation of the 6K and E1 proteins reside in the C-terminal regions of p62 and 6K, respectively. We present evidence suggesting that the polyprotein is processed on the luminal side by signal peptidase at consensus cleavage sites immediately following the signal sequences. Our results also lead us to conclude that the 6K protein is a transmembrane polypeptide with its N terminus on the luminal side of the membrane (type I). Thus, the production of all three membrane proteins is directed by alternating signal and stop-transfer (anchor) sequences that function in translocation and cleavage of the virus precursor polyprotein. This also shows conclusively that internally located signal sequences can be cleaved by signal peptidase.",,"['Liljeström, P', 'Garoff, H']",,,,
,PMC,"The relationship between viral RNA, myelin-specific mRNAs, and demyelination in central nervous system disease during Theiler's virus infection.",,PMC1877742,,,"The DA strain of Theiler's murine encephalomyelitis virus (DAV) causes a chronic demyelinating disease in susceptible mouse strains. To elucidate the pathogenesis of DAV-induced demyelination, the authors investigated the spatial and chronologic relationship between virus (antigen and RNA), myelin-specific mRNAs, and demyelination in DAV-infected mice using immunohistochemistry, in situ hybridization, and slot blot hybridization analyses. In spinal cord white matter, viral RNA was detected easily in ventral root entry zones 1 to 2 weeks after infection. Viral RNA increased to maximum levels by 4 weeks after infection, which was associated with inflammation and mild demyelination. At 8 to 12 weeks after infection, when demyelination became most extensive, viral RNA was significantly decreased. Demyelination did not chronologically or spatially parallel the presence of viral RNA within the spinal cord. Decrease of myelin-specific mRNAs, including myelin-basic protein and proteolipid protein mRNAs, was observed within the demyelinating lesions with or without detectable viral RNA. These results indicate that a viral infection of white matter in the early phase of the infection initiates spinal cord disease leading to demyelination, but later an ongoing immunopathologic process contributes to the presence of extensive demyelination.",,"['Yamada, M.', 'Zurbriggen, A.', 'Fujinami, R. S.']",,,,
,PMC,Cold comfort for the catarrhal child.,,PMC1793095,,,,,"Isaacs, D",,,,
,PMC,Severe proliferative and necrotizing pneumonia in pigs: A newly recognized disease,,PMC1480892,,,,,"['Morin, Michel', 'Girard, Christiane', 'ElAzhary, Youssef', 'Fajardo, Raoul', 'Drolet, Richard', 'Lagacé, André']",,,,
,PMC,Frame shift mutations as a novel mechanism for the generation of neutralization resistant mutants of human respiratory syncytial virus.,,PMC552194,,,"The genetic characterization of four previously reported mutants of human respiratory syncytial (RS) virus resistant to monoclonal antibody 63G is described. Sequences of the G protein genes were obtained from: (i) mRNA derived cDNA recombinants, (ii) direct mRNA sequencing and (iii) amplified vRNA derived cDNAs. The results obtained indicate that the original escape mutants, recovered from individual plaques, contained heterogeneous viral populations. This heterogeneity affected the number of adenosine residues present after nucleotides 588 or 623 of the G protein gene. Mutant viruses recovered after a second plaque purification step generated homogeneous sequences but contained single adenosine insertions or deletions at those two sites compared with the Long sequence. These genetic alterations introduced frameshift changes which are reflected in both the antigenic and structural properties of the mutant G proteins. The origin and importance of frameshift mutations in the RS virus G protein gene are discussed.",,"['García-Barreno, B', 'Portela, A', 'Delgado, T', 'López, J A', 'Melero, J A']",,,,
,PMC,An in vitro system for the leader-primed transcription of coronavirus mRNAs.,,PMC552193,,,"We have developed an in vitro transcription system which can utilize exogenous leader RNA for mouse hepatitis virus (MHV) 'leader-primed' mRNA transcription. Cytoplasmic extracts containing viral proteins and template RNA were prepared by lysolecithin permeabilization of MHV-infected cells. Synthetic leader RNA which differed in sequence from the endogenous leader RNA was added to the extracts and demonstrated to be incorporated into MHV mRNAs. Irrespective of the size of leader RNAs added, the exogenous leader RNA was joined to the endogenous mRNA at the same site, which corresponds to a UCUAA pentanucleotide repeat region. Only leader RNAs containing the pentanucleotide sequences could be utilized for transcription. Mismatches between the intergenic site and the exogenous leader sequence within the pentanucleotide repeat region were corrected in the in vitro system. This in vitro system thus established a novel mechanism of leader-primed transcription using exogenous RNA in trans, and suggests the involvement of a specific ribonuclease activity during coronavirus mRNA synthesis.",,"['Baker, S C', 'Lai, M M']",,,,
,PMC,Acute upper respiratory tract viral illness and influenza immunization in homes for the elderly.,,PMC2271825,,,"Occupants of 482 long-stay and 33 short-stay beds in 11 Leicester City Council homes for the elderly were studied during a 30-week period from September 1988 to March 1989 to determine the incidence, aetiology, morbidity, and mortality of acute upper respiratory tract viral infections and the use of influenza vaccine. Influenza immunization rates by home ranged from 15.4 to 90% (mean 45%). There were no differences in the distribution of medical conditions by home. The highest immunization rates were seen in people with chest disease (77%), heart disease (60%), diabetes (56%), and those with three medical conditions (75%). There was an average of 0.7 upper respiratory episodes per bed per annum with a mortality of 3.4% (6/179). Half of all episodes were seen by a general medical practitioner and 81 of 90 (90%) referrals were prescribed antibiotics costing approximately 7.50 pounds per patient. Lower respiratory tract complications developed during 45 (25%) of 179 episodes including 3 of 12 coronavirus infections, 3 of 9 respiratory syncytial virus infections, 2 of 4 adenovirus infections, 1 of 11 rhinovirus infections, but none of 5 influenza infections. Respiratory infections were caused mostly by pathogens other than influenza virus during the influenza period documented nationally. This highlights the role of coronaviruses, respiratory syncytial virus, and unidentified agents in the elderly, and questions the assumptions made in American estimates on the impact of influenza and the value of influenza vaccines.",,"['Nicholson, K. G.', 'Baker, D. J.', 'Farquhar, A.', 'Hurd, D.', 'Kent, J.', 'Smith, S. H.']",,,,
,PMC,Immunogenic peptide comprising a mouse hepatitis virus A59 B-cell epitope and an influenza virus T-cell epitope protects against lethal infection.,,PMC248803,,,"The coronavirus spike protein S is responsible for important biological activities including virus neutralization by antibody, cell attachment, and cell fusion. Recently, we have elucidated the amino acid sequence of an S determinant common in murine coronaviruses (W. Luytjes, D. Geerts, W. Posthumus, R. Meloen, and W. Spaan, J. Virol. 63:1408-1412, 1989). A monoclonal antibody directed to this determinant (MAb 5B19.2) protected mice against acute fatal infection. In this study, BALB/c mice were immunized with a synthetic peptide of 13 amino acids corresponding to the binding site of MAb 5B19.2, which was either extended with an amino acid sequence of influenza virus hemagglutinin or conjugated to keyhole limpet hemocyanin. Both immunogens induced S-specific antibodies in mice, but only the hemagglutinin-peptide construct protected them against lethal challenge. In contrast to mouse hepatitis virus type 4 (MHV-4), MHV-A59 was not neutralized in vitro by MAb 5B19.2. Neither MHV-A59 nor MHV-4 was neutralized in vitro by antibodies comprising by the synthetic peptides. Our results demonstrated that antibodies elicited with a synthetic peptide comprising a B-cell epitope and a T-helper cell determinant can protect mice against an acute fetal mouse hepatitis virus infection.",,"['Koolen, M J', 'Borst, M A', 'Horzinek, M C', 'Spaan, W J']",,,,
,PMC,Analysis of efficiently packaged defective interfering RNAs of murine coronavirus: localization of a possible RNA-packaging signal.,,PMC248778,,,"We have previously shown that most of the defective interfering (DI) RNA of mouse hepatitis virus (MHV) are not packaged into virions. We have now identified, after 21 serial undiluted passages of MHV, a small DI RNA, DIssF, which is efficiently packaged into virions. The DIssF RNA replicated at a high efficiency on its transfection into the helper virus-infected cells. The virus released from the transfected cells interfered strongly with mRNA synthesis and growth of helper virus. cDNA cloning and sequence analysis of DIssF RNA revealed that it is 3.6 kb and consists of sequences derived from five discontinuous regions of the genome of the nondefective virus. The first four regions (domains I to IV) from the 5' end are derived from gene 1, which presumably encodes the RNA polymerase of the nondefective virus. The entire domain I (859 nucleotides) and the first 750 nucleotides of domain II are also present in a previously characterized DI RNA, DIssE, which is not efficiently packaged into virions. Furthermore, the junction between these two domains is identical between the two DI RNAs. The remaining 77 nucleotides at the 3' end of domain II and all of domains III (655 nucleotides) and IV (770 nucleotides) are not present in DIssE RNA. These four domains are derived from gene 1. In contrast, the 3'-most domain (domain V, 447 nucleotides) is derived from the 3' end of the genomic RNA and is also present in DIssE. The comparison of primary sequences and packaging properties between DIsse and DIssF RNAs suggested that domains III and IV and part of the 3' end of domain II contain the packaging signal for MHV RNA. This conclusion was confirmed by inserting these DIssF-unique sequences into a DIssE cDNA construct; the in vitro-transcribed RNA from this hybrid construct was efficiently packaged into virion particles. DIssF RNA also contains an open reading frame, which begins from domain I and ends at the 5'-end 20 bases of domain III. In vitro translation of DIssF RNA and metabolic labeling of the virus-infected cells showed that this open reading frame is indeed translated into a 75-kDa protein. The structures of both DIssE and DIssF RNAs suggest that a protein-encoding capability is a common characteristic of MHV DI RNA.",,"['Makino, S', 'Yokomori, K', 'Lai, M M']",,,,
,PMC,Herpes simplex virus particles are unable to traverse the secretory pathway in the mouse L-cell mutant gro29.,,PMC248713,,,"The mouse L-cell mutant gro29 was selected for its ability to survive infection by herpes simplex virus type 1 (HSV-1) and is defective in the propagation of HSV-1 and vesicular stomatitis virus (F. Tufaro, M. D. Snider, and S. L. McKnight, J. Cell Biol. 105:647-657, 1987). In this report, we show that gro29 cells harbor a lesion that inhibits the egress of HSV-1 virions during infection. We also found that HSV-1 glycoprotein D was slow to traverse the secretory pathway en route to the plasma membrane of infected gro29 cells. The movement of glycoproteins was not blocked entirely, however, and immunofluorescence experiments revealed that infected gro29 cells contained roughly 10% of the expected amount of glycoprotein D on their cell surface at 12 h postinfection. Furthermore, nucleocapsids and virions assembled inside the cells during infection, suggesting that the lesion in gro29 cells impinged on a late step in virion maturation. Electron micrographs of infected cells revealed that many of the intracellular virions were contained in irregular cytoplasmic vacuoles, similar to those that accumulate in HSV-1-infected cells treated with the ionophore monensin. We conclude from these results that gro29 harbors a defect that blocks the egress of HSV-1 virions from the infected cell without seriously impeding the flux of individual glycoproteins to the cell surface. We infer that HSV-1 maturation and egress require a host cell component that is either reduced or absent in gro29 cells and that this lesion, although not lethal to the host cell, cannot be tolerated by HSV-1 during its life cycle.",,"['Banfield, B W', 'Tufaro, F']",,,,
,PMC,"Evaluation of the anti-influenza virus activities of 1,3,4-thiadiazol-2-ylcyanamide (LY217896) and its sodium salt.",,PMC172017,,,"1,3,4-Thiadiazol-2-ylcyanamide (LY217896) and its sodium salt were shown to be effective against influenza A and B viruses in vitro and in the mouse model. In nondividing confluent MDCK cells, the 50% inhibitory concentration of LY217896 ranged from 0.37 to 1.19 micrograms/ml against various strains of influenza A virus and from 0.75 to 1.54 micrograms/ml against various strains of influenza B virus, with no apparent cytotoxicity. However, at a concentration of 0.31 microgram/ml, LY217896 inhibited the replication of dividing MDCK cells. LY217896 (9 mg/m2 of body surface area per day) administered in the diet, in the drinking water, by oral gavage, by intraperitoneal injection, or by aerosolization was well tolerated and protected CD-1 mice infected with a lethal dose of influenza A or B virus. Effective administration of the compound could be delayed for up to 96 h postinfection. Virus titer was reduced by 1 to 2 log10 units in lungs of mice given LY217896 in the drinking water. Mice treated initially with protective levels of LY217896 were resistant to a subsequent challenge of influenza virus in the absence of the compound, indicating that the animals were able to develop immunity to the initial infection. Administration of LY217896 to uninfected mice did not induce interferon-like activity or interfere with natural killer cell function. In the ferret, LY217896 was effective in preventing fever induced by influenza virus.",,"['Colacino, J M', 'DeLong, D C', 'Nelson, J R', 'Spitzer, W A', 'Tang, J', 'Victor, F', 'Wu, C Y']",,,,
,PMC,A comparison of three oral electrolyte solutions in the treatment of diarrheic calves,,PMC1480882,,,"Thirty-six diarrheic calves infected with rota- and coronaviruses were randomly allocated to one of three oral electrolyte treatments: Ion-Aid (Syntex Agribusiness), Life-Guard (Norden Inc), or Revibe (Langford Inc). The calves were also allowed voluntary access to milk which was offered at the rate of 5% of body weight per feeding in two feedings daily. There were significant differences in recovery rate among calves treated with the different electrolytes. Only 33% of Ion-Aid-treated calves recovered; Revibe- and Life-Guard-treated calves had high recovery rates of 92% and 83%, respectively. The much higher recovery rates with Life-Guard and Revibe were attributed to the presence of an alkalizing agent in these preparations. Life-Guard uses bicarbonate to counteract acidosis and there was some evidence that this may have interfered with milk digestion. Revibe uses acetate; this was effectively metabolized within the calves' tissues and produced alkalization without interference with milk digestion.",,"['Naylor, Jonathan M.', 'Petrie, Lyall', 'Rodriguez, Maria I.', 'Skilnick, Patricia']",,,,
,PMC,Genetic relationships among strains of avian Escherichia coli associated with swollen-head syndrome.,,PMC313705,,,"Genetic diversity among 22 Escherichia coli strains isolated from chickens with swollen-head syndrome (SHS), an acute respiratory disease of domestic poultry, and 93 strains isolated from birds with colibacillosis was assessed on the basis of allelic variation at 20 enzyme-encoding loci detected by multilocus enzyme electrophoresis. SHS isolates from Spain and Canada were polymorphic at 14 loci and were classified into 19 multilocus genotypes, defining clones that differed on average at 34% of the loci. In most cases, SHS isolates of different clonal genotypes were distinct in O:H serotype and expressed different fimbrial antigens. Comparisons with 93 isolates obtained from birds with colibacillosis revealed enzyme polymorphisms at 17 of 20 loci, with an average of 3.5 alleles per locus. In the total sample, 56 clonal genotypes were distinguished, with 27 (23%) of the isolates belonging to one of three common clones. Both SHS and colibacillosis isolates were genetically diverse, with an average single-locus diversity of 0.36, indicating that a wide variety of naturally occurring bacterial clones is associated with these acute avian infections. Six previously defined groups of clones identified in diseased birds from the United States were represented in isolates from Spain, indicating that similar clones occur in widely separated geographic areas. In addition, one group of SHS isolates was closely related to a recognized widespread clone complex incriminated in human septicemia and meningitis. The results suggest that certain strains implicated in SHS infections belong to a clone complex whose members have special attributes that promote involvement in invasive diseases in humans and animals.",,"['White, D G', 'Wilson, R A', 'Gabriel, A S', 'Saco, M', 'Whittam, T S']",,,,
,PMC,L-tryptophan implicated in human eosinophilia-myalgia syndrome causes fasciitis and perimyositis in the Lewis rat.,,PMC296930,,,"Tryptophan-associated eosinophilia-myalgia syndrome (L-TRP-EMS) is a newly described syndrome which occurred in epidemic fashion in the United States in the summer and fall of 1989. Epidemiologic data has linked the syndrome to intake of L-tryptophan (L-TRP) from one specific manufacturer, but the precise etiologic compound(s) must be established by replication of the syndrome in an appropriate animal model. In this study, implicated L-TRP, United States Pharmacopeia (USP) grade L-TRP, or vehicle was administered by gavage in a blinded fashion for 38 d to female Lewis rats at doses comparable with those ingested by patients who developed the eosinophilia-myalgia syndrome. Animals receiving implicated L-TRP, but not those receiving USP grade L-TRP or vehicle, developed histologic signs consistent with fasciitis and perimyositis, specific pathologic features of human L-TRP-EMS. Peripheral blood eosinophilia was not observed. Hypothalamic corticotropin releasing hormone mRNA levels were lower and plasma corticosterone levels tended to be lower in the animals that received implicated L-TRP. Plasma L-kynurenine was higher in both L-TRP-treated groups compared to the vehicle-treated animals. The female Lewis rat is known to be susceptible to a wide variety of inflammatory diseases. Identification of specific inflammatory changes in this rat following exposure to implicated L-TRP indicates that this animal model will be important in subsequent investigations into the etiology, pathogenesis, and treatment of human L-TRP-EMS.",,"['Crofford, L J', 'Rader, J I', 'Dalakas, M C', 'Hill, R H', 'Page, S W', 'Needham, L L', 'Brady, L S', 'Heyes, M P', 'Wilder, R L', 'Gold, P W']",,,,
,PMC,Glucocorticoids inhibit neurogenic plasma extravasation and prevent virus-potentiated extravasation in the rat trachea.,,PMC296883,,,"Capsaicin increases the permeability of blood vessels in the rat tracheal mucosa through a mechanism involving the release of tachykinins from sensory nerves. This capsaicin-induced increase in vascular permeability is potentiated by viral infections of the respiratory tract. The present study was done to determine whether this ""neurogenic plasma extravasation"" can be inhibited by glucocorticoids, to learn the time course of this inhibition, and to determine whether glucocorticoids can prevent the potentiating effect of viral respiratory infections on neurogenic plasma extravasation. Groups of pathogen-free F344 rats were treated with dexamethasone for 2 or 8 h (4 mg/kg i.p.) or 48 or 120 h (0.5-4 mg/kg per d i.p.). Another group of rats was treated with dexamethasone for 120 h following the intranasal inoculation of Sendai virus. The magnitude of plasma extravasation produced by capsaicin or substance P was assessed after this treatment by using Monastral blue pigment and Evans blue dye as intravascular tracers. We found that dexamethasone reduced, in a dose-dependent fashion, the magnitude of plasma extravasation produced in the rat trachea by capsaicin and substance P. Significant inhibition was produced by a dose of dexamethasone as small as 0.5 mg/kg i.p. The effect of dexamethasone had a latency of several hours and reached a maximum after 2 d of treatment. Furthermore, dexamethasone prevented the potentiation of neurogenic plasma extravasation usually present after 5 d of Sendai virus respiratory infection.",,"['Piedimonte, G', 'McDonald, D M', 'Nadel, J A']",,,,
,PMC,Serotypic differentiation of group A rotaviruses with porcine rotavirus gene 9 probes.,,PMC268219,,,"The serotypic specificities of Gottfried and OSU porcine rotavirus gene 9 probes were investigated in a dot hybridization assay. The probes were reacted with homologous and heterologous serotypes of group A rotaviruses of human and animal origin. Hybridizations were conducted under relatively low-stringency (52 degrees C, no formamide, 5 x SSC) and high-stringency (52 degrees C, 50% formamide, formamide, 5 x SSC) conditions (1 x SSC is 0.15 M NaCl plus 0.015 M sodium citrate). Under conditions of relatively low stringency, the Gottfried and OSU gene 9 probes demonstrated broad cross-reactivity and were useful in the detection of homologous and heterologous serotypes of group A rotaviruses. Under conditions of relatively high stringency, the Gottfried and OSU gene 9 probes were serotype specific. The Gottfried gene 9 probe (serotype 4) hybridized with homologous Gottfried porcine rotavirus as well as the serotype 4 human rotaviruses ST3 and VA70. The OSU gene 9 probe (serotype 5) hybridized with homologous OSU porcine rotavirus and the serotype 5 equine rotavirus H1. Hybridization was not observed with the antigenically distinct group B and C porcine rotaviruses or with other porcine enteric viruses, including calicivirus and a coronavirus, transmissible gastroenteritis virus, regardless of stringency conditions. Analysis of 14 group A rotavirus-positive field samples resulted in the serotypic differentiation, collectively, of six serotype 4 or 5 porcine rotaviruses. No field samples reacted with both the Gottfried and OSU gene 9 probes.",,"['Rosen, B I', 'Saif, L J', 'Jackwood, D J', 'Gorziglia, M']",,,,
,PMC,Lymphocyte subset alterations and viral determinants of immunodeficiency disease induction by the feline leukemia virus FeLV-FAIDS.,,PMC248598,,,"The FeLV-FAIDS strain of feline leukemia virus consistently induces fatal immunodeficiency. To investigate the immunopathogenesis and viral genetic determinants responsible for the induction of immunodeficiency disease in vivo, we have generated chimeras between the two major viral genomes in the original virus isolate, designated common form clone 61E and major variant clone 61C, which were molecularly cloned directly from DNA of the same animal and tissue. Each of three 61E/C chimeras, containing at minimum a 34-amino-acid segment (including a 6-amino-acid insertion and one amino acid substitution) near the C terminus of the 61C surface glycoprotein (gp70), induced fatal immunodeficiency disease in all (12 of 12) infected animals over a course of 33 +/- 10 weeks. By contrast, animals infected with virus 61E, although persistently antigenemic, remained asymptomatic throughout a 48-week observation period. Beginning 14 weeks after infection, a significant decrease (8 to 10%) in the percent of circulating CD4+ T lymphocytes developed in the 61E/C chimera-infected cats, compared with either 61E-infected or control animals. At this time, no significant changes were seen in CD8 cells, B cells, or mitogen-induced blastogenesis. Prior to this initial decline in CD4 cells, the ability of all antigenemic 61E/C-infected cats to generate a primary antibody response to the T-cell-dependent antigen keyhole limpet hemocyanin was markedly impaired, whereas all 61E-infected cats, one 61E/C-infected but nonviremic cat, and all uninfected control cats produced normal antibody responses. The results reported here demonstrate that a major determinant of in vivo immunodeficiency induction by FeLV-FAIDS is contained within a 34-amino-acid C-terminal segment of its surface glycoprotein and that this gp70 alteration determines the early and persistent deficits in CD4+ T lymphocytes and T-cell-dependent antibody responses. We hypothesize that these early immunologic alterations could result from early deletion of a CD4+ helper T-cell subset.",,"['Quackenbush, S L', 'Donahue, P R', 'Dean, G A', 'Myles, M H', 'Ackley, C D', 'Cooper, M D', 'Mullins, J I', 'Hoover, E A']",,,,
,PMC,Assembly of coronavirus spike protein into trimers and its role in epitope expression.,,PMC248586,,,"The folding and oligomerization of coronavirus spike protein were explored using a panel of monoclonal antibodies. Chemical cross-linking and sedimentation experiments showed that the spike of transmissible gastroenteritis virus is a homotrimer of the S membrane glycoprotein. The spike protein was synthesized as a 175,000-apparent-molecular-weight (175K) monomer subunit that is sensitive to endo-beta-N-acetylglucosaminidase H. Assembly of monomers into a trimeric structure was found to occur on a partially trimmed polypeptide and to be a rate-limiting step, since large amounts of monomers failed to trimerize 1 h after completion of synthesis. Terminal glycosylation of newly assembled trimers, resulting in the biosynthesis of three 220K oligomers, occurred with a half time of approximately 20 min. Monomeric (230K to 240K) processed forms were also observed in cells and in virions. The 175K monomeric form expressed four major antigenic sites previously localized within the amino-terminal half of the S polypeptide chain; however, two classes of trimer-restricted epitopes (borne by three 220K and/or three 175K oligomers) were identified. The S glycoprotein of coronavirus might be a valuable model system for discovering new aspects of the maturation of membrane glycoproteins.",,"['Delmas, B', 'Laude, H']",,,,
,PMC,Viral bronchiolitis during early life induces increased numbers of bronchiolar mast cells and airway hyperresponsiveness.,,PMC1877564,,,"The objectives of this study were to determine the kinetics of Sendai virus-induced increases in bronchiolar mast cells and to determine whether virus-induced increases in bronchiolar mast cells were associated with increased airway responsiveness to methacholine and with altered allergic inflammatory responses to antigen stimulation. Mast cell density in intrapulmonary airways was measured in outbred CD (Crl:CDBR) rats by use of morphometric techniques at 7, 15, 30, 60, and 90 days after viral or sham inoculation. Density of bronchiolar mast cells was higher in virus-inoculated rats than in control rats at 30, 60, and 90 days after inoculation (P less than 0.01), but not at 7 or 15 days after inoculation. Total pulmonary mast cell numbers were increased in virus-inoculated rats at 30 days after inoculation. Rats at 42 days after viral inoculation had over a threefold increase in sensitivity to the concentration of nebulized metbacholine that would stimulate a 50% increase in respiratory resistance. Virus-inoculated rats sensitized to ovalbumin had over a 10-fold increase (P less than 0.02) in pulmonary neutrophils that were recovered by bronchoalveolar lavage at 4 hours after ovalbumin aerosol challenge. Virus-inoculated rats at this time also had higher densities of neutrophils in bronchiolar walls than allergen-exposed control rats. The results indicate that Sendai virus induces increases in numbers of bronchiolar mast cells at times from 30 to 90 days after inoculation, and that mast cell increases are associated with airway hyperresponsiveness to methacholine and heightened allergic airway inflammatory reactions.",,"['Castleman, W. L.', 'Sorkness, R. L.', 'Lemanske, R. F.', 'McAllister, P. K.']",,,,
,PMC,Experimental infection of young rabbits with a rabbit enteric coronavirus.,,PMC1255696,,,"The clinical signs and lesions caused by the rabbit enteric coronavirus (RECV) were studied in young rabbits orally inoculated with a suspension containing RECV particles. The inoculated animals were observed daily for evidence of diarrhea. Fecal samples and specimens from the small intestine and from the gut associated lymphoid tissue (GALT) were collected from 2 h to 29 days postinoculation (PI) and processed for immune electron microscopy (IEM) and light microscopy. Coronavirus particles were detected in the cecal contents of most inoculated animals from 6 h to 29 days PI. Lesions were first observed 6 h PI and were characterized by a loss of the brush border of mature enterocytes located at the tips of intestinal villi and by necrosis of these cells. At 48 h PI, short intestinal villi and hypertrophic crypts were noted. In the GALT, complete necrosis of the M cells as well as necrosis of the enterocytes lining the villi above the lymphoid follicules with hypertrophy of the corresponding crypts were observed in all the animals. Five inoculated rabbits had diarrhea three days PI. The presence of RECV particles in the feces of the sick animals and the microscopic lesions observed in the small intestine suggested that the virus was responsible for the clinical signs. A few inoculated rabbits remained free of diarrhea. Fecal material collected at postmortem examination contained RECV particles. The results suggest that the virus could also produce a subclinical infection.",,"['Descôteaux, J P', 'Lussier, G']",,,,
,PMC,Some infectious causes of diarrhea in young farm animals.,,PMC358168,,,"Escherichia coli, rotaviruses, and Cryptosporidium parvum are discussed in this review as they relate to enteric disease in calves, lambs, and pigs. These microorganisms are frequently incriminated as causative agents in diarrheas among neonatal food animals, and in some cases different strains or serotypes of the same organism cause diarrhea in humans. E. coli causes diarrhea by mechanisms that include production of heat-labile or heat-stable enterotoxins and synthesis of potent cytotoxins, and some strains cause diarrhea by yet undetermined mechanisms. Rotaviruses and C. parvum induce various degrees of villous atrophy. Rotaviruses infect and replicate within the cytoplasm of enterocytes, whereas C. parvum resides in an intracellular, extracytoplasmic location. E. coli, rotavirus, and C. parvum infections are of concern to producers, veterinarians, and public health officials. These agents are a major cause of economic loss to the producer because of costs associated with therapy, reduced performance, and high morbidity and mortality rates. Moreover, diarrheic animals may harbor, incubate, and act as a source to healthy animals and humans of some of these agents.",,"Holland, R E",,,,
,PMC,The time course of the immune response to experimental coronavirus infection of man.,,PMC2271881,,,"After preliminary trials, the detailed changes in the concentration of specific circulating and local antibodies were followed in 15 volunteers inoculated with coronavirus 229E. Ten of them, who had significantly lower concentrations of pre-existing antibody than the rest, became infected and eight of these developed colds. A limited investigation of circulating lymphocyte populations showed some lymphocytopenia in infected volunteers. In this group, antibody concentrations started to increase 1 week after inoculation and reached a maximum about 1 week later. Thereafter antibody titres slowly declined. Although concentrations were still slightly raised 1 year later, this did not always prevent reinfection when volunteers were then challenged with the homologous virus. However, the period of virus shedding was shorter than before and none developed a cold. All of the uninfected group were infected on re-challenge although they also appeared to show some resistance to disease and in the extent of infection. These results are discussed with reference to natural infections with coronavirus and with other infections, such as rhinovirus infections.",,"['Callow, K. A.', 'Parry, H. F.', 'Sergeant, M.', 'Tyrrell, D. A.']",,,,
,PMC,Selective modulation of the natural killer activity of murine intestinal intraepithelial leucocytes by the neuropeptide substance P.,,PMC1384303,,,"Neuropeptides can influence immune effector cell function at both systemic and mucosal immune sites. We examined the ability of substance P (SP) to modulate the natural killer (NK) activity of intestinal intraepithelial leucocytes (IEL). Yac-1 killing by IEL but not splenic cells was increased after either 18 hr preincubation or 6 hr of co-incubation with SP. We also examined the NK activity of IEL and spleen isolated from mice treated with SP in vivo. The selective increase in NK activity of IEL occurred without any demonstrable change in the number or phenotype of the IEL. The IEL responsive to SP in vivo and induced in vivo by SP were both Thy-1- and did not kill the NK insensitive mastocytoma cell line P815. Lastly, we examined the ability of SP to induce the release of interleukin-2 (IL-2) and IL-4 from IEL after 6 and 18 hr of in vitro culture. No increase in the release of these cytokines was observed, suggesting that IL-2 and IL4 are not involved in the local augmentation of IEL NK activity by SP. These observations suggest that SP has a selective stimulatory effect on intestinal activity and may play a role in the regulation of intestinal cell-mediated immunity.",,"['Croitoru, K', 'Ernst, P B', 'Bienenstock, J', 'Padol, I', 'Stanisz, A M']",,,,
,PMC,Murine coronavirus nonstructural protein ns2 is not essential for virus replication in transformed cells.,,PMC247966,,,"Two isolates of the murine hepatitis virus (MHV) strain JHM, which differed in their ability to express the nonstructural gene product ns2, were characterized. The MHV Wb3 isolate encodes a 30,000-molecular-weight ns2 protein that can be readily detected in infected cells by using a specific monoclonal antibody, MAb 2A. The MHV Wb1 isolate is a deletion mutant that lacks a functional ns2 gene and the transcriptional signals required for the synthesis of an ns2 mRNA. However, there are no obviously significant differences in the growth of the MHV Wb1 and MHV Wb3 isolates in continuous cell lines or in the synthesis of viral mRNAs or proteins in infected cells. These results demonstrate that the ns2 gene product is not essential for MHV replication in transformed murine cells and suggests that the function of the ns2 gene may only be manifest in vivo.",,"['Schwarz, B', 'Routledge, E', 'Siddell, S G']",,,,
,PMC,Genetic basis for the pathogenesis of transmissible gastroenteritis virus.,,PMC247963,,,"Intracellular RNAs of an avirulent small-plaque (SP) transmissible gastroenteritis virus variant and the parent virulent Miller strain of transmissible gastroenteritis virus were compared. Northern RNA blotting showed that the Miller strain contained eight intracellular RNA species. RNAs 1, 2(S), 5, 6(M), 7(N), and 8 were similar in size for both viruses; however, the SP variant lacked subgenomic RNAs 3 and 4. Instead, the SP virus contained an altered RNA species (delta 4) that was slightly smaller than RNA 4. S1 nuclease protection experiments showed a deletion of approximately 450 nucleotides in the SP genome downstream of the peplomer S gene. Sequencing of cDNA clones confirmed that SP virus contained a 462-nucleotide deletion, eliminating the transcriptional recognition sequences for both RNAs 3 and 4. These RNAs encode open reading frames A and B, respectively. An alternative consensus recognition sequence was not readily apparent for the delta 4 RNA species of SP virus. Since open reading frame A is missing in SP virus, it is not essential for a productive infection. The status of the potential protein encoded by open reading frame B is not clear, because it may be missing or just truncated. Nevertheless, these genes appear to be the contributing entities for transmissible gastroenteritis virus virulence, SP morphology, tissue tropism, and/or persistence in swine leukocytes.",,"['Wesley, R D', 'Woods, R D', 'Cheung, A K']",,,,
,PMC,Effective clearance of mouse hepatitis virus from the central nervous system requires both CD4+ and CD8+ T cells.,,PMC247935,,,"Both CD4+ and CD8+ T cells are required for the clearance of virus from the central nervous system following infection with the JHM strain of mouse hepatitis virus. Development of antiviral antibodies requires the presence of CD4+ T cells but appears to play a minimal role in the reduction of virus. The data presented are consistent with the hypothesis that clearance of JHM virus is mediated by virus-specific CD8+ T cells, which appear to require the presence of CD4+ T cells.",,"['Williamson, J S', 'Stohlman, S A']",,,,
,PMC,"In vitro processing of dengue virus type 2 nonstructural proteins NS2A, NS2B, and NS3.",,PMC247904,,,"We have tested the hypothesis that the flavivirus nonstructural protein NS3 is a viral proteinase that generates the termini of several nonstructural proteins by using an efficient in vitro expression system and monospecific antisera directed against the nonstructural proteins NS2B and NS3. A series of cDNA constructs was transcribed by using T7 RNA polymerase, and the RNA was translated in reticulocyte lysates. The resulting protein patterns indicated that proteolytic processing occurred in vitro to generate NS2B and NS3. The amino termini of NS2B and NS3 produced in vitro were found to be the same as the termini of NS2B and NS3 isolated from infected cells. Deletion analysis of cDNA constructs localized the protease domain within NS3 to the first 184 amino acids but did not eliminate the possibility that sequences within NS2B were also required for proper cleavage. Kinetic analysis of processing events in vitro and experiments to examine the sensitivity of processing to dilution suggested that an intramolecular cleavage between NS2A and NS2B preceded an intramolecular cleavage between NS2B and NS3. The data from these expression experiments confirm that NS3 is the viral proteinase responsible for cleavage events generating the amino termini of NS2B and NS3 and presumably for cleavages generating the termini of NS4A and NS5 as well.",,"['Preugschat, F', 'Yao, C W', 'Strauss, J H']",,,,
,PMC,Inhibition of antigen-induced and interleukin-2-induced proliferation of bovine peripheral blood leukocytes by inactivated bovine herpes virus 1.,,PMC247878,,,"The mechanism by which bovine herpesvirus 1 (BHV-1) predisposes cattle to bacterial pneumonia was investigated by using an in vitro system to demonstrate immunosuppression. At a multiplicity of infection of 0.001, live or inactivated BHV-1 induced a 50% inhibition of the proliferative response of peripheral blood mononuclear leukocytes to antigen (vaccinia virus in vaccinia virus-immunized cattle which were BHV-1 negative) or interleukin-2. At this same multiplicity of infection, the mitogen-induced proliferation of peripheral blood mononuclear leukocytes was unaffected. This inhibition of antigen and interleukin-2-induced proliferative responses could not be reversed by the addition of excess amounts of interleukin-2 and could not be prevented by the addition of indomethacin to block prostaglandin production. Antibodies to BHV-1, especially those specific for glycoproteins gI and gIV, were able to block the inhibitory effect of BHV-1 in these in vitro assays. These results showed that antibody to BHV-1 blocks the immunosuppressive effect of the virus in vitro and suggested that an appropriate antibody response to BHV-1 could protect cattle from virus-induced immunosuppression leading to secondary bacterial pneumonia.",,"['Hutchings, D L', 'Campos, M', 'Qualtiere, L', 'Babiuk, L A']",,,,
,PMC,Bovine coronavirus mRNA replication continues throughout persistent infection in cell culture.,,PMC247873,,,"The existence of viral mRNA replicons was demonstrated in cells infected with the bovine coronavirus by showing a minus-strand counterpart and a corresponding replicative intermediate for each subgenomic mRNA species. mRNA replication is thus a universal property of coronaviruses, since this is now the third coronavirus for which it has been demonstrated. During the acute phase of infection (first 48 h), minus and plus strands accumulated at the same rate initially, but maximal accumulation of minus strands peaked earlier than that for plus strands, indicating that minus- and plus-strand levels are differentially regulated. In addition, packaged (input) mRNAs appeared to serve as templates for their own early replication. mRNA replication continued throughout establishment and maintenance of persistent infection (studied for 120 days), which is consistent with our hypothesis that mRNA replication contributes mechanistically to virus persistence. A replication-defective (potentially interfering) species of RNA existed transiently (beginning at day 2 and ending before day 76 postinfection), but because of its transient nature it cannot be considered essential to the long-term maintenance of virus persistence.",,"['Hofmann, M A', 'Sethna, P B', 'Brian, D A']",,,,
,PMC,Characterization of hepatitis delta antigen: specific binding to hepatitis delta virus RNA.,,PMC247866,,,"It has previously been shown that human hepatitis virus delta antigen has an RNA-binding activity (Chang et al., J. Virol. 62:2403-2410, 1988). In the present study, the specificity of such an RNA-protein interaction was demonstrated by expressing various domains of the delta antigen in Escherichia coli as TrpE fusion proteins and testing their RNA-binding activities in a Northwestern protein-RNA immunoblot assay and RNA gel mobility shift assay. Hepatitis delta virus (HDV) RNA bound specifically to the delta antigen in the presence of an excess amount of unrelated RNAs and a relatively high salt concentration. Both genome- and antigenome-sense HDV RNAs and at least two different regions of HDV genomic RNA bound to the delta antigen. Surprisingly, these two different regions of HDV genomic RNA could compete with each other for delta antigen binding, although they do not have common nucleotide sequences. In contrast, this binding could not be competed with by other viral or cellular RNA. Since both the genomic and antigenomic HDV RNAs had strong intramolecular complementary sequences, these results suggest that the binding of delta antigen is probably specific for a secondary structure unique to the HDV RNA. By expressing different subdomains of the delta antigen, we found that the middle one-third of delta antigen was responsible for binding HDV RNA. Neither the N-terminal nor the C-terminal domain bound HDV RNA. Binding between the delta antigen and HDV RNA was also demonstrated within the HDV particles isolated from the plasma of a human delta hepatitis patient. This in vivo binding resisted treatment with 0.1% sodium dodecyl sulfate and 0.5% Nonidet P-40. In addition, we showed that the antiserum from a human patient with delta hepatitis reacted with all three subdomains of the delta antigen, indicating that all of the domains are immunogenic in vivo. These studies demonstrated the specific interaction between delta antigen and HDV RNA.",,"['Lin, J H', 'Chang, M F', 'Baker, S C', 'Govindarajan, S', 'Lai, M M']",,,,
,PMC,The E1 glycoprotein of an avian coronavirus is targeted to the cis Golgi complex.,,PMC54658,,,"It was previously reported that the E1 protein of an avian coronavirus was targeted to the juxtanuclear region in COS cells expressing the protein from cloned cDNA, suggesting that the protein contains information for targeting to the Golgi complex. The first of three membrane-spanning domains was required for intracellular targeting, because a mutant E1 (delta m1,2) lacking this domain was delivered to the plasma membrane. We have used immunoelectron microscopy to localize the wild-type E1 protein within Golgi elements of COS cells and AtT-20 cells expressing these proteins from recombinant vaccinia vectors. By immunoperoxidase and immunogold labeling, the wild-type E1 protein was localized to one or two cisternae located on one side of the Golgi stack that could be identified as the cis side in AtT-20 cells. In contrast, the mutant E1 protein was detected in all cisternae across the stack as well as at the plasma membrane. When the E1 proteins were immunoprecipitated and subjected to digestion with endoglycosidase H, the majority of the wild-type E1 glycoprotein was endoglycosidase H sensitive, whereas the majority of the mutant E1 was processed to an endoglycosidase H-resistant, polylactosaminoglycan-containing form. The findings indicate that the wild-type E1 protein is specifically targeted to cis Golgi cisternae and are consistent with the assumption that the first membrane-spanning domain is required for targeting to the cis Golgi.",,"['Machamer, C E', 'Mentone, S A', 'Rose, J K', 'Farquhar, M G']",,,,
,PMC,Trans-splicing of pre-mRNA is predicted to occur in a wide range of organisms including vertebrates.,,PMC331928,,,"Several known trans-splicing RNA structures were used to define a canonical trans-splicing structure which was then used to perform a computer search of the EMBL nucleotide database. In addition to most known trans-splicing structures, many putative new trans-splicing sites were detected. These were found in a broad range of organisms including the vertebrates. Control experiments indicate that the search predicts known false positives at a rate of only 20%. Trans-splicing may therefore be a very wide-spread phenomenon.",,"['Dandekar, T', 'Sibbald, P R']",,,,
,PMC,The carboxyl-terminal part of the putative Berne virus polymerase is expressed by ribosomal frameshifting and contains sequence motifs which indicate that toro- and coronaviruses are evolutionarily related.,,PMC331274,,,"Sequence analysis of the 3' part (8 kb) of the polymerase gene of the torovirus prototype Berne virus (BEV) revealed that this area contains at least two open reading frames (provisionally designated ORF1a and ORF1b) which overlap by 12 nucleotides. The complete sequence of ORF1b (6873 nucleotides) was determined. Like the coronaviruses, BEV was shown to express its ORF1b by ribosomal frameshifting during translation of the genomic RNA. The predicted tertiary RNA structure (a pseudoknot) in the toro- and coronaviral frameshift-directing region is similar. Analysis of the amino acid sequence of the predicted BEV ORF1b translation product revealed homology with the ORF1b product of coronaviruses. Four conserved domains were identified: the putative polymerase domain, an area containing conserved cysteine and histidine residues, a putative helicase motif, and a domain which seems to be unique for toro- and coronaviruses. The data on the 3' part of the polymerase gene of BEV supplement previously observed similarities between toro- and coronaviruses at the level of genome organization and expression. The two virus families are more closely related to each other than to other families of positive-stranded RNA viruses.",,"['Snijder, E J', 'den Boon, J A', 'Bredenbeek, P J', 'Horzinek, M C', 'Rijnbrand, R', 'Spaan, W J']",,,,
,PMC,Eukaryotic coupled translation of tandem cistrons: identification of the influenza B virus BM2 polypeptide.,,PMC552297,,,"Previous nucleotide sequence analysis of RNA segment 7 of influenza B virus indicated that, in addition to the reading frame encoding the 248 amino acid M1 protein, there is a second overlapping reading frame (BM2ORF) of 585 nucleotides that has the coding capacity for 195 amino acids. To search for a polypeptide product derived from BM2ORF, a genetically engineered beta-galactosidase-BM2ORF fusion protein was expressed in Escherichia coli and a polyclonal rabbit antiserum was raised to the purified fusion protein. This antiserum was used to identify a polypeptide, designated BM2 protein (Mr approximately equal to 12,000), that is synthesized in influenza B virus-infected cells. To understand the mechanism by which the BM2 protein is generated from influenza B virus RNA segment 7, a mutational analysis of the cloned DNA was performed and the altered DNAs were expressed in eukaryotic cells. The expression patterns of the M1 and BM2 proteins from the altered DNAs indicate that the BM2 protein initiation codon overlaps with the termination codon of the M1 protein in an overlapping translational stop-start pentanucleotide, TAATG, and that the expression of the BM2 protein requires 5'-adjacent termination of M1 synthesis. Our data suggest that a termination-reinitiation scheme is used in translation of a bicistronic mRNA derived from influenza B virus RNA segment 7, and this strategy has some analogy to prokaryotic coupled stop-start translation of tandem cistrons.",,"['Horvath, C M', 'Williams, M A', 'Lamb, R A']",,,,
,PMC,Human T-cell leukemia virus type I trans activator induces class I major histocompatibility complex antigen expression in glial cells.,,PMC249700,,,"Transfection of the tax gene encoding the trans activator of human T-cell leukemia virus type I into glial line cells induced class I major histocompatibility complex (MHC) antigens on these cells. This occurred through the interaction of tax protein with the gene encoding class I MHC antigens but not through any soluble factors, such as interferons, or factors from glial cells. Since neural cells do not usually express MHC antigens, this novel mechanism may be an intermediate event between viral infection and subsequent immune-mediated pathology in the central nervous system.",,"['Sawada, M', 'Suzumura, A', 'Yoshida, M', 'Marunouchi, T']",,,,
,PMC,"Purification of the 110-kilodalton glycoprotein receptor for mouse hepatitis virus (MHV)-A59 from mouse liver and identification of a nonfunctional, homologous protein in MHV-resistant SJL/J mice.",,PMC249677,,,"The receptor for mouse hepatitis virus strain A59 (MHV-A59) is a 110- to 120-kilodalton (kDa) glycoprotein which is expressed in MHV-susceptible mouse strains on the membranes of hepatocytes, intestinal epithelial cells, and macrophages. SJL/J mice, which are highly resistant to MHV-A59, were previously shown to lack detectable levels of receptor by using either solid-phase virus receptor assays or binding of a monoclonal anti-receptor antibody (MAb) which blocks infection of MHV-susceptible mouse cells. This MAb was used for affinity purification of the receptor glycoprotein from livers of MHV-susceptible Swiss Webster mice. The MHV receptor and an antigenically related protein of 48 to 58 kDa were copurified and then separated by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The first 15 amino acids of the receptor were sequenced, and a synthetic peptide of this amino acid sequence was prepared. Rabbit antiserum made against this peptide bound to the MHV receptor glycoprotein and the 48- to 58-kDa protein from livers of MHV-susceptible BALB/c mice and Swiss Webster mice and from the intestinal brush border of BALB/c mice. In immunoblots of intestinal brush border and hepatocyte membranes of MHV-resistant SJL/J mice, the antibody against the amino terminus of the receptor identified proteins that are 5 to 10 kDa smaller than the MHV receptor and the 48- to 58-kDa related protein from Swiss Webster or BALB/c mice. Thus, SJL/J mice express a protein which shares some sequence homology with the MHV receptor but which lacks virus-binding activity and is not recognized by the blocking anti-receptor MAb. These results suggest that resistance of SJL/J mice to MHV-A59 may be due to absence or mutation of the virus-binding domain in the nonfunctional receptor homolog in SJL/J mice.",,"['Williams, R K', 'Jiang, G S', 'Snyder, S W', 'Frana, M F', 'Holmes, K V']",,,,
,PMC,Defective assembly and intracellular transport of mutant paramyxovirus hemagglutinin-neuraminidase proteins containing altered cytoplasmic domains.,,PMC249653,,,"The hemagglutinin-neuraminidase (HN) integral membrane protein of paramyxoviruses is expressed at the cell surface as a tetramer consisting of a pair of disulfide-linked dimers. HN has a large C-terminal ectodomain, a 19-residue uncleaved signal-anchor domain, and a 17-residue N-terminal cytoplasmic tail. Various mutant HN genes were constructed to examine the role of residues flanking the signal-anchor domain, including the cytoplasmic tail, on assembly and intracellular transport of the HN glycoprotein. Expression of the altered genes showed that by 90 min after synthesis the majority of the mutant HN proteins were in a conformationally mature form as assayed by their reactivity with conformation-specific monoclonal antibodies. However, the mutant proteins showed varied endoplasmic reticulum-to-Golgi apparatus transport rates, ranging from that of wild-type HN (t1/2 approximately 90 min) to slowly transported molecules (t1/2 approximately 5 h) and to molecules in which transport was not detected. Pulse-chase experiments indicated that the altered HN molecules had a specific and transient interaction with the resident endoplasmic reticulum protein GRP78-BiP, and thus the altered HN molecules were not retained in the endoplasmic reticulum by a prolonged interaction with GRP78-BiP. Sucrose density gradient sedimentation analysis of the mutant HN molecules indicated that they all had an oligomeric form that differed from that of wild-type HN; most of the molecules were found as disulfide-linked dimers rather than as tetramers. These data suggest that the HN cytoplasmic tail may function in the assembly of the final transport-competent oligomeric form of HN and that mutant HN molecules with seemingly properly folded ectodomains are retained in the endoplasmic reticulum by an as yet unidentified mechanism. The possible role of the HN cytoplasmic tail as a signal for intracellular transport is discussed.",,"['Parks, G D', 'Lamb, R A']",,,,
,PMC,cDNA sequence analysis of a 29-kDa cysteine-rich surface antigen of pathogenic Entamoeba histolytica.,,PMC54533,,,"A gamma gt11 cDNA library was constructed from poly(U)-Sepharose-selected Entamoeba histolytica trophozoite RNA in order to clone and identify surface antigens. The library was screened with rabbit polyclonal anti-E. histolytica serum. A 700-base-pair cDNA insert was isolated and the nucleotide sequence was determined. The deduced amino acid sequence of the cDNA revealed a cysteine-rich protein. DNA hybridizations showed that the gene was specific to E. histolytica since the cDNA probe reacted with DNA from four axenic strains of E. histolytica but did not react with DNA from Entamoeba invadens, Acanthamoeba castellanii, or Trichomonas vaginalis. The insert was subcloned into the expression vector pGEX-1 and the protein was expressed as a fusion with the C terminus of glutathione S-transferase. Purified fusion protein was used to generate 22 monoclonal antibodies (mAbs) and a mouse polyclonal antiserum specific for the E. histolytica portion of the fusion protein. A 29-kDa protein was identified as a surface antigen when mAbs were used to immunoprecipitate the antigen from metabolically 35S-labeled live trophozoites. The surface location of the antigen was corroborated by mAb immunoprecipitation of a 29-kDa protein from surface-125I-labeled whole trophozoites as well as by the reaction of mAbs with live trophozoites in an indirect immunofluorescence assay performed at 4 degrees C. Immunoblotting with mAbs demonstrated that the antigen was present on four axenic isolates tested. mAbs recognized epitopes on the 29-kDa native antigen on some but not all clinical isolates tested.",,"['Torian, B E', 'Flores, B M', 'Stroeher, V L', 'Hagen, F S', 'Stamm, W E']",,,,
,PMC,New nucleotide sequence data on the EMBL File Server,,PMC331241,,,,,,,,,
,PMC,Anti-idiotypic antibodies induce neutralizing antibodies to bovine herpesvirus 1.,,PMC1384154,,,"A neutralizing murine monoclonal antibody (mAb) of the IgG2a isotype (MM-113), specific for bovine herpesvirus 1 (BHV-1) glycoprotein gIV, was used to develop anti-idiotypic antibodies (anti-Id) in a calf. The bovine anti-Id were isolated from the serum of the immunized calf by affinity chromatography on an MM-113-Sepharose column, followed by repeated adsorption on a murine IgG2a column. The anti-Id thus obtained specifically reacted with MM-113, but not with isotype-matched controls. They also inhibited the binding of MM-113 to BHV-1 in a concentration-dependent manner. Mice immunized with the anti-Id produced neutralizing antibodies to BHV-1. The anti-Id bound to cells permissive to BHV-1 in a cell-binding radioimmunoassay (RIA).",,"['Srikumaran, S', 'Onisk, D V', 'Borca, M V', 'Nataraj, C', 'Zamb, T J']",,,,
,PMC,"Transposition in Shigella dysenteriae: isolation and analysis of IS911, a new member of the IS3 group of insertion sequences.",,PMC213396,,,"Twenty-nine clear-plaque mutants of bacteriophage lambda were isolated from a Shigella dysenteriae lysogen. Three were associated with insertions in the cI gene: two were due to insertion of IS600, and the third resulted from insertion of a new element, IS911. IS911 is 1,250 base pairs (bp) long, carries 27-bp imperfect terminal inverted repeats, and generates 3-bp duplications of the target DNA on insertion. It was found in various copy numbers in all four species of Shigella tested and in Escherichia coli K-12 but not in E. coli W. Analysis of IS911-mediated cointegrate molecules indicated that the majority were generated without duplication of IS911. They appeared to result from direct insertion via one end of the element and the neighboring region of DNA, which resembles a terminal inverted repeat of IS911. Nucleotide sequence analysis revealed that IS911 carries two consecutive open reading frames which code for potential proteins showing similarities to those of the IS3 group of elements.",,"['Prère, M F', 'Chandler, M', 'Fayet, O']",,,,
,PMC,Productive infection of isolated human alveolar macrophages by respiratory syncytial virus.,,PMC296697,,,"Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract disease in children and individuals with cell-mediated immunodeficiencies. Airway epithelial cells may be infected with RSV, but it is unknown whether other cells within the lung permit viral replication. We studied whether human alveolar macrophages supported RSV replication in vitro. Alveolar macrophages exposed to RSV demonstrated expression of RSV fusion gene, which increased in a time-dependent manner and correlated with RSV protein expression. RSV-exposed alveolar macrophages produced and released infectious virus into supernatants for at least 25 d after infection. Viral production per alveolar macrophage declined from 0.053 plaque-forming units (pfu)/cell at 24 h after infection to 0.003 pfu/cell by 10 d after infection and then gradually increased. The capability of alveolar macrophages to support prolonged RSV replication may have a role in the pulmonary response to RSV infection.",,"['Panuska, J R', 'Cirino, N M', 'Midulla, F', 'Despot, J E', 'McFadden, E R', 'Huang, Y T']",,,,
,PMC,Inability of mitogen-activated lymphocytes obtained from patients with malignant primary intracranial tumors to express high affinity interleukin 2 receptors.,,PMC296693,,,"Patients with primary malignant brain tumors manifest a variety of abnormalities in cell-mediated and humoral immunity. Diminished T cell reactivity has been shown in these patients to be linked to deficiencies in interleukin 2 (IL-2) production that cannot be overcome by exogenous IL-2. In this study, specific binding of radiolabeled IL-2 to PHA-stimulated lymphocytes from brain tumor patients demonstrates that the number of high affinity interleukin 2 receptors (IL-2R) is greatly reduced. FACS analysis indicates that the relative density of the p55 protein (Tac protein) is lower on the mitogen-activated lymphocytes obtained from patients than on comparably treated lymphocytes from normal individuals. These data indicate that mitogen-stimulated lymphocytes obtained from patients have fewer functional high affinity IL-2R principally because of the failure to express sufficient levels of the p55 protein for association with the p75 protein. Northern analysis of total RNA isolated from mitogen-stimulated T cells from patients demonstrates normal levels of steady state mRNA, which codes for the p55 protein. Moreover, there is no defect in the postranslational processing of the primary translation product of this mRNA suggesting that normal levels of the p55 protein are produced in activated T cells from patients.",,"['Elliott, L H', 'Brooks, W H', 'Roszman, T L']",,,,
,PMC,Analysis and simulation of a neutralizing epitope of transmissible gastroenteritis virus.,,PMC249563,,,"The amino acid sequences recognized by monoclonal antibodies (MAbs) specific for the antigenic site IV of the spike protein S of transmissible gastroenteritis virus were analyzed by PEPSCAN. All MAbs of group IV recognized peptides from the S region consisting of residues 378 to 390. In addition, the neutralizing MAbs (subgroup IV-A) also bound to peptides from the region consisting of residues 1173 to 1184 and to several other peptides with a related amino acid composition. The contribution of the individual residues of both sequences to the binding of a MAb was determined by varying the length of the peptide and by a consecutive deletion or replacement of parental residues by the 19 other amino acids. The sequence consisting of residues 326 to 558, tested as part of a cro-beta-galactosidase hybrid protein, was antigenic, but the sequence consisting of residues 1150 to 1239 was not. Furthermore, antibodies raised in rabbits against the peptide SDSSFFSYGEIPFGN (residues 377 to 391), but not those raised against the peptide VRASRQLAKDKVNEC (residues 1171 to 1185), recognized the virus and had neutralizing activity. We infer that the epitope of the neutralizing MAbs is composite and consists of the linear sequence SFFSYGEI (residues 380 to 387) with contributions of A, D, K, N, Q, or V residues from other parts of the S molecule. The complex epitope was simulated by synthesizing peptides in which the sequences consisting of residues 380 to 387 and 1176 to 1184 were combined. MAbs of subgroup IV-A recognized the combination peptides two to six times better than the individual sequences. These results may offer prospects for the development of an experimental vaccine.",,"['Posthumus, W P', 'Lenstra, J A', 'Schaaper, W M', 'van Nieuwstadt, A P', 'Enjuanes, L', 'Meloen, R H']",,,,
,PMC,Transcriptional slippage occurs during elongation at runs of adenine or thymine in Escherichia coli.,,PMC331007,,,"A run of 11 adenine or thymine residues at the 5' end of an out-of-frame lacZ gene causes a high level of beta-galactosidase expression in E. coli. This effect was not observed for a run of guanine residues. Reverse transcription of mRNA isolated from E. coli containing the run of 11 A's reveals heterogeneity of transcript length while reverse transcription of mRNA isolated from S. cerevisiae containing the same gene shows no heterogeneity. Protein sequencing of the beta-galactosidase molecules derived from the out-of-frame construct containing a run of adenines reveals the addition of a lysine at the run. A new method was developed where messages small enough to allow resolution of single nucleotide differences on an acrylamide gel are electrophoresed, electroblotted onto nylon and probed. This confirmed the reverse transcription results and showed that additional residues can be added to transcripts derived from DNA containing 10 or 11 thymine residues. A mechanism for slippage is discussed where the A-U rich RNA-DNA hybrid can denature during elongation and rehybridize in an offset position, causing the addition of extra residues to the transcript.",,"['Wagner, L A', 'Weiss, R B', 'Driscoll, R', 'Dunn, D S', 'Gesteland, R F']",,,,
,PMC,All subgenomic mRNAs of equine arteritis virus contain a common leader sequence.,,PMC330929,,,During the replication of equine arteritis virus (EAV) six subgenomic mRNAs are synthesized. We present evidence that the viral mRNAs form a 3'-coterminal nested set and contain a common leader sequence of 208 nucleotides which is encoded by the 5'-end of the genome. The leader is joined to the bodies of mRNA 5 and 6 at positions defined by the sequence 5' UCAAC 3'. The part of the leader sequence flanking the UCAAC motif is very similar to the 5'-splice site of the Tetrahymena pre-rRNA. A possible internal guide sequence has been identified 43 nucleotides downstream of the leader sequence on the genome. Hybridization analysis shows that all EAV intracellular RNAs contain the leader sequence. These data imply that the viral subgenomic mRNAs are composed of leader and body sequences which are non-contiguous on the genome.,,"['de Vries, A A', 'Chirnside, E D', 'Bredenbeek, P J', 'Gravestein, L A', 'Horzinek, M C', 'Spaan, W J']",,,,
,PMC,Rapid viral diagnosis in perspective.,,PMC1663153,,,,,"['Lee, P C', 'Hallsworth, P']",,,,
,PMC,Pathogenicity for humans of human rhinovirus type 2 mutants resistant to or dependent on chalcone Ro 09-0410.,,PMC171738,,,"Mutants of human rhinovirus type 2 (HRV-2) resistant to and dependent on the antirhinoviral compound chalcone Ro 09-0410 were selected in cell culture under clean laboratory conditions. A total of 42 volunteers were challenged with either the drug-resistant mutant [SR2-410(r)] (15 volunteers), the drug-dependent mutant [SR2-410(d)] (15 volunteers), or a wild-type HRV-2 which had a similar passage level in vitro as the mutants but without the drug (12 volunteers). Of volunteers challenged with the wild-type HRV-2, 33, 67, and 82% developed cold symptoms, shed virus, and showed serological evidence of infection, respectively. In contrast, only 13, 27, and 23% of volunteers challenged with the drug-resistant mutant developed colds, shed virus, and showed serological evidence of infection, respectively. None of the volunteers challenged with the drug-dependent virus became infected or had symptoms of colds. These results demonstrate that a drug-resistant rhinovirus was capable of infecting humans and producing disease, although its infectivity was reduced when compared with that of the wild type. In contrast, a drug-dependent virus had lost its ability to infect humans.",,"['Yasin, S R', 'al-Nakib, W', 'Tyrrell, D A']",,,,
,PMC,Porcine group C rotavirus as a cause of neonatal diarrhea in a Quebec swine herd.,,PMC1255675,,,"A porcine group C rotavirus was found to be the unique cause of a problem of enzootic neonatal diarrhea in a minimal disease herd composed of 190 sows on a continuous farrowing program. During the outbreaks of diarrhea, 10 to 80% of the litters were affected with a morbidity rate of 100% and case fatality rates of 5 to 10%. Clinical signs began 24 to 48 h after birth and were characterized by a profuse yellow diarrhea lasting a few days. Piglets from different outbreaks of diarrhea were necropsied. They had multifocal villous atrophy in the small intestine, especially in the ileum. Group C rotavirus was demonstrated by direct immunofluorescent staining of frozen intestinal sections and by polyacrylamide gel electrophoresis of viral RNA extracted from the intestinal contents of diarrheic piglets. The infection with clinical illness and lesions was reproduced experimentally in newborn piglets by oral inoculation of a suspension prepared from a pool of intestinal contents from diarrheic piglets.",,"['Morin, M', 'Magar, R', 'Robinson, Y']",,,,
,PMC,Detection of coronavirus-like particles from mink with epizootic catarrhal gastroenteritis.,,PMC1255674,,,Coronavirus-like particles have been detected by electron microscopy in fecal samples from naturally occurring cases of epizootic catarrhal gastroenteritis (ECG) of mink. Preliminary transmission trials with bacteria-free filtrates from mink with ECG suggested that a coronavirus plays a role in the disease syndrome.,,"['Gorham, J R', 'Evermann, J F', 'Ward, A', 'Pearson, R', 'Shen, D', 'Hartsough, G R', 'Leathers, C']",,,,
,PMC,Risk factors for mortality from diarrhea in beef calves in Alberta.,,PMC1255671,,,"A case-study involving 56 randomly selected beef herds in Alberta was conducted to assess the association of a number of suspected risk factors upon the odds of a high mortality from diarrhea among calves less than 30 days of age. Using stepwise logistic regression it was found that an increased percentage of heifers calving in the herd, poor drainage in the nursing area, providing limited shelter in the nursing area, a large calving area, and wintering cows and heifers on the same ground were conditionally associated with an increase in the odds of high mortality from neonatal diarrhea.",,"['Schumann, F J', 'Townsend, H G', 'Naylor, J M']",,,,
,PMC,The induction and characterization of natural porcine interferons alpha and beta.,,PMC1255668,,,"The purpose of this study was to define optimum conditions for the production of high concentrations of natural porcine interferon (POIFN)-alpha and POIFN-beta, and to characterize the IFNs which were produced. The inducers used were Newcastle disease virus (NDV), polyinosinic:polycytidylic acid (poly IC), poly IC complexed with diethylaminoethyl dextran (poly IC-DEAEdx) and poly IC complexed with poly-L-lysine and carboxymethylcellulose. The highest yields of POIFN-alpha were obtained from porcine peripheral blood leukocyte (PBL) cultures induced with NDV. The concentrations of both cells and virus were critical for high yields of IFN, which were also enhanced by priming. Poly IC was found to be a relatively poor IFN inducer in PBL, in which low yields were obtained only after priming or in response to poly IC-DEAEdx. POIFN-beta was prepared by induction of the PK-15 cell line with poly IC or poly IC-DEAEdx. The highest yields were obtained from cultures induced 24 h after seeding, although when poly IC-DEAEdx or superinduction was used, the age of the cells was less critical. Priming had little effect on the yields of POIFN-beta. PK-15 cells induced with NDV gave relatively low yields of IFN. Both POIFN-alpha and POIFN-beta were classified as type I IFN on the basis of their resistance or susceptibility to pH 2.0, ultracentrifugation, 56 degrees C and trypsin treatment. Disulphide bonds essential for antiviral activity were demonstrated in both types of IFN by reduction with 2-beta-mercaptoethanol, and anionic exchange chromatography after treatment with dithiothreitol indicated a second disulphide bond in POIFN-alpha which was not essential for antiviral activity.(ABSTRACT TRUNCATED AT 250 WORDS)",,"['Weingartl, H M', 'Derbyshire, J B']",,,,
,PMC,Monoclonal antibodies to the p80/125 gp53 proteins of bovine viral diarrhea virus: their potential use as diagnostic reagents.,,PMC1255667,,,"Monoclonal antibodies reactive to the bovine viral diarrhea virus (BVDV) protein gp53 were produced and characterized. These antibodies and our panel of anti-p80/125 monoclonal antibodies were tested for their cross-reactivity with 11 different North American and European (Danish) BVDV strains and isolates including viruses of both cytopathic and noncytopathic biotypes. The four anti-gp53 monoclonal antibodies were neutralizing for the homologous Danish cytopathic isolate and cross-reacted with all BVDV strains examined except for the Draper strain. Further, anti-gp53 monoclonal antibodies neutralized the majority of BVDV strains examined. The anti-p80/125 monoclonal antibodies cross-reacted with all eleven strains and isolates tested. This indicated that various strains of BVDV have common epitopes. The broad cross-reactivities demonstrated by these monoclonal antibodies suggest that a pool of these antibodies may be used for detection of BVDV cellular contamination or for virus isolation, in place of polyclonal antiserum.",,"['Deregt, D', 'Masri, S A', 'Cho, H J', 'Bielefeldt Ohmann, H']",,,,
,PMC,Detection of antibody to avian viruses in human populations.,,PMC2271774,,,"The ability of three avian viruses to elicit antibody response in humans was surveyed for the purpose of identifying zoonotic diseases. Antibody levels in people associated with poultry were compared to those in people having limited poultry association. Antibody levels to three avian viruses: infectious bursal disease virus, a birnavirus; Newcastle disease virus, a paramyxovirus; and avian infectious bronchitis virus, a coronavirus were determined by enzyme-linked immunosorbent assays (ELISA). Differences between the two study groups were evident: people having a known association with poultry showed significantly higher levels of antibodies to Newcastle disease and avian infectious bronchitis virus. Antibodies detected may be due to virus exposure rather than zoonoses.",,"['Pedersden, K. A.', 'Sadasiv, E. C.', 'Chang, P. W.', 'Yates, V. J.']",,,,
,PMC,Disparate mechanisms of induction of procoagulant activity by live and inactivated bacteria and viruses.,,PMC258730,,,"This study describes the dose response, time course, and lymphocyte requirements of procoagulant activity (PCA) induction following stimulation of thioglycolate-elicited BALB/c peritoneal macrophages with live and inactivated bacteria (Bacteroides fragilis, Escherichia coli, and Staphylococcus aureus) and murine hepatitis virus type 3 (MHV-3). Induction of PCA by MHV-3 was significantly more rapid and the maximal PCA achieved was significantly greater than by the three bacterial species studied. In relation to induction of PCA by bacteria, the PCA response was more rapid and of greater magnitude with S. aureus and E. coli than with B. fragilis. MHV-3 induced an augmented PCA response at all concentrations of virus studied in a dose-dependent fashion, whereas higher titers of live bacteria (greater than 10(7) CFU/ml) inhibited PCA, suggesting the production of an inhibitory factor. Significant PCA induction was observed when macrophages were incubated with bacteria or virus in the absence of lymphocytes. At low titers of B. fragilis (10(3) CFU/ml), addition of lymphocytes greatly augmented PCA production, whereas at higher titers (10(7) CFU/ml), the addition of lymphocytes only slightly augmented the PCA response. In contrast, MHV-3 induction of PCA was enhanced by the addition of lymphocytes at all concentrations of virus studied, suggesting a lymphocyte-dependent process. Heat-inactivated bacteria were as effective as live bacteria in inducing PCA, suggesting that induction of PCA by bacteria requires only a bacterial surface component. In contrast, UV-inactivated MHV-3 did not induce PCA, suggesting that viral replication is a necessary step in PCA induction. These results suggest that the cellular and metabolic requirements for induction of PCA differ among viral and bacterial pathogens and may partly explain their differences in pathogenicity.",,"['Sinclair, S B', 'Rotstein, O D', 'Levy, G A']",,,,
,PMC,Cell culture propagation of a coronavirus isolated from cows with winter dysentery.,,PMC267955,,,"Fecal filtrates from cows with winter dysentery were inoculated into gnotobiotic and conventional calves, and a coronavirus was isolated from calf feces. Cytopathic effects were observed on human rectal tumor cells but not bovine cell cultures. The winter dysentery isolates morphologically and antigenically resembled the Mebus strain of bovine coronavirus.",,"['Benfield, D A', 'Saif, L J']",,,,
,PMC,Antigenic and genomic relationships among turkey and bovine enteric coronaviruses.,,PMC249505,,,"Antigenic and genomic relationships among tissue culture-adapted turkey enteric coronavirus (TCV) isolates, three strains of avian infectious bronchitis virus (IBV), and mammalian coronaviruses were investigated. Immunoblotting and immunoprecipitation experiments using polyclonal antisera showed that the four major structural proteins of TCV cross-reacted with the four homologous proteins of bovine enteric coronavirus (BCV), the N and M proteins of mouse hepatitis virus serotype 3, and the N protein of IBV. Close antigenic relationships between TCV and BCV were also established by seroneutralization and hemagglutination-inhibition. Of 49 monoclonal antibodies produced against either TCV or BCV, 11 differentiated the two viruses. Five of these monoclonal antibodies had neutralizing activities and were directed to either the peplomeric S (gp200-gp100) or hemagglutinin HE (gp140-gp65) glycoproteins. BCV cDNA probes tested on purified viral preparations and coronavirus-positive (by electron microscopy) fecal samples from diarrheic turkey poults confirmed the relatedness of TCV and BCV. The two viruses produced distinct cytopathic changes in HRT-18 cells in the presence of trypsin, whereas only TCV isolates were able to reproduce the clinical symptoms in turkey poults. Their matrix (M) proteins undergo different glycosylation processes.",,"['Dea, S', 'Verbeek, A J', 'Tijssen, P']",,,,
,PMC,Monoclonal antibodies to the peplomer glycoprotein of coronavirus mouse hepatitis virus identify two subunits and detect a conformational change in the subunit released under mild alkaline conditions.,,PMC249490,,,"Monoclonal antibodies (MAbs) directed against the E2 glycoprotein of mouse hepatitis virus (MHV) have been classified according to their ability to bind to either of the two purified 90,000-molecular-weight subunits (90K subunits) of the 180K peplomeric glycoprotein E2. Correlation with previously reported information about these MAbs suggest that both of the subunits of E2 are important for viral infectivity and cell fusion. Incubation of trypsin-treated virions at pH 8.0 and 37 degrees C released only the E2N subunit from virions. The pattern of MAb reactions suggested that a conformational change occurred in the E2N subunit in association with its release from virions under mildly alkaline conditions at 37 degrees C, the same conditions which are optimal for coronavirus-induced cell fusion.",,"['Weismiller, D G', 'Sturman, L S', 'Buchmeier, M J', 'Fleming, J O', 'Holmes, K V']",,,,
,PMC,Conformational change of the coronavirus peplomer glycoprotein at pH 8.0 and 37 degrees C correlates with virus aggregation and virus-induced cell fusion.,,PMC249489,,,"We have obtained biochemical and electron microscopic evidence of conformational changes at pH 8.0 and 37 degrees C in the coronavirus spike glycoprotein E2 (S). The importance of these changes is reflected in the loss of virus infectivity, the aggregation of virions, and increased virus-induced cell fusion at the same pH. Coronavirus (MHV-A59) infectivity is exquisitely sensitive to pH. The virus was quite stable at pH 6.0 and 37 degrees C (half-life, approximately 24 h) but was rapidly and irreversibly inactivated by brief treatment at pH 8.0 and 37 degrees C (half-life, approximately 30 min). Virions treated at pH 8.0 and 37 degrees C formed clumps and large aggregates. With virions treated at pH 8.0 and 37 degrees C, the amino-terminal peptide E2N (or S1) was released from virions and the remaining peptide, E2C (S2), was aggregated. Viral spikes isolated from detergent-treated virions also aggregated at pH 8.0 and 37 degrees C. Loss of virus infectivity and E2 (S) aggregation at pH 8.0 and 37 degrees C were markedly enhanced in the presence of dithiothreitol. On the basis of the effects of dithiothreitol on the reactions of the peplomer, we propose that release of E2N (S1) and aggregation of E2C (S2) may be triggered by rearrangement of intramolecular disulfide bonds. The aggregation of virions and the isolated E2 (S) glycoprotein at pH 8.0 and 37 degrees C or following treatment with guanidine and urea at pH 6.0 and 37 degrees C indicate that an irreversible conformational change has been induced in the peplomer glycoprotein by these conditions. It is interesting that coronavirus-induced cell fusion also occurred under mildly alkaline conditions and at 37 degrees C. Some enveloped viruses, including influenza viruses and alphaviruses, show conformational changes of spike glycoproteins at a low pH, which correlates with fusion and penetration of those viruses in acidified endocytic vesicles. For coronavirus MHV-A59, comparable conformational change of the spike glycoprotein E2 (S) and cell fusion occurred at a mildly alkaline condition, suggesting that coronavirus infection-penetration, like that of paramyxoviruses and lentiviruses, may occur at the plasma membrane, rather than within endocytic vesicles.",,"['Sturman, L S', 'Ricard, C S', 'Holmes, K V']",,,,
,PMC,Molecular structure of the cell-attachment protein of reovirus: correlation of computer-processed electron micrographs with sequence-based predictions.,,PMC249483,,,"The receptor-recognition interaction that initiates reovirus infection is mediated by the sigma 1 protein, located at the vertices of the icosahedral virion. We have applied computer-based image-averaging techniques to electron micrographs of negatively stained preparations of sigma 1 purified from virions (serotype 2 Jones). Combining these results with inferences based on the amino acid sequence has led to a molecular model in which the overall folding of the chains is described; its conformation embodies motifs, coiled-coil alpha-helices and nodular multichain elements rich in beta-sheets, previously detected in the corresponding proteins of other viruses, but with some novel variations. Sigma 1 is a filamentous lollipop-shaped molecule with an overall length of approximately 48 nm; it has a flexible ""tail,"" approximately 40 nm long by 4 to 6 nm wide, terminating at its distal end in a globular ""head,"" approximately 9.5 nm in diameter. The purified protein is a tetramer (4 by 50 kilodaltons) consisting of two similarly oriented dimers bonded side by side and in register. For each chain, a cluster of hydrophobic residues at its amino terminus resides at the proximal end of the tail; next, an alpha-helical domain (residues 25 to 172) participates in a two-chained coiled coil, 22 nm long, with two such coiled coils pairing laterally to form the proximal half of the tail. The remainder of the tail (residues 173 to approximately 316) is less uniform in width and is expected to be rich in beta-sheet; the interdimer bonding is evidently sustained through this portion of the molecule. Finally, the globular head consists of the carboxy-terminal domains (which contain the receptor-binding sites) folded into compact globular conformations; in appropriate side views, the head is resolved into two subunits, presumably contributed by the respective dimers. This model for how the four sigma 1 polypeptide chains are threaded in parallel through the fiber is supported by the observed match between an empirical curvature profile, which identifies the locations of relatively flexible sites along the tail, and the flexibility profile predicted on the basis of the model. Appraisal of the interactions that stabilize the coiled coils suggests that (i) the alpha-helices are individually only marginally stable, a property that may be of significance with regard to the retracted conformation in which sigma 1 is accommodated in the intact virion, and (ii) the predominant interactions between the two coiled coils are likely to involve hydrogen bonding between patches of uncharged residues.",,"['Fraser, R D', 'Furlong, D B', 'Trus, B L', 'Nibert, M L', 'Fields, B N', 'Steven, A C']",,,,
,PMC,Hemagglutinin mutations related to attenuation and altered cell tropism of a virulent avian influenza A virus.,,PMC249478,,,"The H5 hemagglutinin (HA) of a highly virulent avian influenza virus, A/Turkey Ontario/7732/66 (H5N9), was previously shown to have five neutralizing epitopes, and escape mutants within one epitope (group 1) were markedly attenuated (M. Philpott, B. C. Easterday, and V. S. Hinshaw, J. Virol. 63:3453-3458, 1989). To define the genetic changes related to these antigenic and biologic properties, the HA genes of mutants within each of the epitope groups were sequenced by using the polymerase chain reaction. The mutations in the attenuated group 1 mutants were located near the distal tip of the HA molecule in close proximity to the receptor-binding site, on the basis of alignment with the three-dimensional structure of the H3 HA. All group 1 mutations involved charged amino acids. The group 1 mutants, similar to the wild-type virus, spread systemically and were recovered from the spleens of infected chickens but, unlike the wild-type virus, failed to produce severe necrosis in the spleens. Viral replication in the spleens was investigated by in situ hybridization of spleen sections from chickens infected with the wild-type or attenuated mutants. Wild-type virus replication was demonstrated in large, mononuclear, macrophagelike cells; however, group 1 mutant virus was detected attached only to erythrocytes within the red pulp. These results suggest that the attenuated mutants differ in their cell tropism within the spleen.",,"['Philpott, M', 'Hioe, C', 'Sheerar, M', 'Hinshaw, V S']",,,,
,PMC,Neurovirulence determinants of genetically engineered Theiler viruses.,,PMC54060,,,"Theiler murine encephalomyelitis viruses (TMEVs) are picornaviruses that cause enteric and neurological disease in mice. The GDVII strain and other members of the GDVII subgroup are highly virulent and cause an acute, fatal polioencephalomyelitis following intracerebral inoculation, whereas the DA stain and other members of the TO subgroup cause a persistent, demyelinating infection. We previously produced a full-length, infectious DA cDNA clone. We now describe the generation of a full-length, infectious GDVII cDNA clone and the subsequent production of intratypic chimeric cDNAs and intratypic recombinant viruses. Inoculation of the recombinant viruses into mice demonstrated that a major determinant of TMEV neurovirulence is within the GDVII 1B (capsid protein VP2)-2C coding region, most likely in the GDVII 1B (VP2)-2A coding region. Genomic sequences 5' to this region of GDVII RNA also contribute to expression of the full neurovirulence phenotype. These data demonstrate the multigenic nature of TMEV neurovirulence, as has been reported for other viruses.",,"['Fu, J L', 'Stein, S', 'Rosenstein, L', 'Bodwell, T', 'Routbort, M', 'Semler, B L', 'Roos, R P']",,,,
,PMC,"Nucleotide and amino acid sequence of the S1 subunit of the spike glycoprotein of avian infectious bronchitis virus, strain D3896.",,PMC330853,,,,,"['Koch, G', 'Kant, A']",,,,
,PMC,Campylobacter jejuni abortions in two beef cattle herds in Saskatchewan,,PMC1480707,,,"Abortions, accompanied by placental retention and weight loss, occurred during February and March in 19% of 120 and 10% of 108 beef cows and heifers on two neighboring ranches in southern Saskatchewan. A diagnosis of Campylobacter jejuni abortion was made based on lesions of necrotizing and suppurative placentitis and fetal bronchopneumonia in association with the culture of large numbers of C. jejuni from placentas and fetal tissues. Campylobacter jejuni was isolated with variable frequency from fecal samples of aborting and healthy cows, and scouring and healthy calves. Campylobacter jejuni serotype 2 (Lior) was isolated from fetal tissues and feces of a scouring calf, whereas C. jejuni serotypes 1, 4, 5 and 99 were isolated from feces of in-contact cattle. We hypothesized that the source and mode of transmission of C. jejuni was fecal contamination of water supplies and feeding grounds by carrier cows or wildlife.",,"['Van Donkersgoed, Joyce', 'Janzen, Eugene D.', 'Chirino-Trejo, Manuel', 'Berry, Catherine', 'Clark, Edward G.', 'Haines, Deborah M.']",,,,
,PMC,HPV or human parvovirus?,,PMC502473,,,,,"Ronalds, C J",,,,
,PMC,Prevalence and implications of feline coronavirus infections of captive and free-ranging cheetahs (Acinonyx jubatus).,,PMC249350,,,"The extent and progression of exposure to feline infectious peritonitis (FIP) virus in the cheetah, Acinonyx jubatus, was monitored by a world-wide serological survey with indirect fluorescent antibody titers to coronavirus. The indirect fluorescent antibody assay was validated by Western blots, which showed that all indirect fluorescent antibody-positive cheetah sera detected both domestic cat and cheetah coronavirus structural proteins. There was a poor correlation between indirect fluorescent antibody results and the presence of coronaviruslike particles in cheetah feces, suggesting that electron microscopic detection of shed particles may not be an easily interpreted diagnostic parameter for FIP disease. Low, but verifiable (by Western blots [immunoblots]) antibody titers against coronavirus were detected in eight free-ranging cheetahs from east Africa as well as from captive cheetahs throughout the world. Of 20 North American cheetah facilities screened, 9 had cheetahs with measurable antibodies to feline coronavirus. Five facilities showed patterns of an ongoing epizootic. Retrospective FIP virus titers of an FIP outbreak in a cheetah-breeding facility in Oregon were monitored over a 5-year period and are interpreted here in terms of clinical disease progression. During that outbreak the morbidity was over 90% and the mortality was 60%, far greater than any previously reported epizootic of FIP in any cat species. Age of infection was a significant risk factor in this epizootic, with infants (less than 3 months old) displaying significantly higher risk for mortality than subadults or adults. Based upon these observations, empirical generalizations are drawn which address epidemiologic concerns for cheetahs in the context of this lethal infectious agent.",,"['Heeney, J L', 'Evermann, J F', 'McKeirnan, A J', 'Marker-Kraus, L', 'Roelke, M E', 'Bush, M', 'Wildt, D E', 'Meltzer, D G', 'Colly, L', 'Lukas, J']",,,,
,PMC,Short related sequences in the cytoplasmic domains of CD4 and CD8 mediate binding to the amino-terminal domain of the p56lck tyrosine protein kinase.,,PMC360530,,,"We report that the cytoplasmic domains of the T-lymphocyte glycoproteins CD4 and CD8 alpha contain short related amino acid sequences that are involved in binding the amino-terminal domain of the intracellular tyrosine protein kinase, p56lck. Transfer of as few as six amino acid residues from the cytoplasmic domain of the CD8 alpha protein to the cytoplasmic domain of an unrelated protein conferred p56lck binding to the hybrid protein in HeLa cells. The common sequence motif shared by CD4 and CD8 alpha contains two cysteines, and mutation of either cysteine in the CD4 sequence eliminated binding of p56lck.p56lck also contains two cysteine residues within its CD4-CD8 alpha-binding domain, and both are critical to the interaction with CD4 or CD8 alpha. Because the interaction does not involve disulfide bond formation, a metal ion could stabilize the complex.",,"['Shaw, A S', 'Chalupny, J', 'Whitney, J A', 'Hammond, C', 'Amrein, K E', 'Kavathas, P', 'Sefton, B M', 'Rose, J K']",,,,
,PMC,New nucleotide sequence data on the EMBL File Server,,PMC330735,,,,,,,,,
,PMC,The primary structure and expression of the second open reading frame of the polymerase gene of the coronavirus MHV-A59; a highly conserved polymerase is expressed by an efficient ribosomal frameshifting mechanism.,,PMC330602,,,Sequence analysis of a substantial part of the polymerase gene of the murine coronavirus MHV-A59 revealed the 3' end of an open reading frame (ORF1a) overlapping with a large ORF (ORF1b; 2733 amino acids) which covers the 3' half of the polymerase gene. The expression of ORF1b occurs by a ribosomal frameshifting mechanism since the ORF1a/ORF1b overlapping nucleotide sequence is capable of inducing ribosomal frameshifting in vitro as well as in vivo. A stem-loop structure and a pseudoknot are predicted in the nucleotide sequence involved in ribosomal frameshifting. Comparison of the predicted amino acid sequence of MHV ORF1b with the amino acid sequence deduced from the corresponding gene of the avian coronavirus IBV demonstrated that in contrast to the other viral genes this ORF is extremely conserved. Detailed analysis of the predicted amino acid sequence revealed sequence elements which are conserved in many DNA and RNA polymerases.,,"['Bredenbeek, P J', 'Pachuk, C J', 'Noten, A F', 'Charité, J', 'Luytjes, W', 'Weiss, S R', 'Spaan, W J']",,,,
,PMC,Programmed ribosomal frameshifting generates the Escherichia coli DNA polymerase III gamma subunit from within the tau subunit reading frame.,,PMC330589,,,"The Escherichia coli dnaX gene encodes both the tau and gamma subunits of DNA polymerase III holoenzyme in one reading frame. The 71.1 kDa tau and the shorter gamma share N-terminal sequences. Mutagenesis of a potential ribosomal frameshift signal located at codons 428-430 without changing the amino acid sequence of the tau product, eliminated detectable synthesis of the gamma subunit, suggesting that the reading frame is shifted at that sequence and gamma is terminated by a nonsense codon located in the -1 frame 3 nucleotides downstream of the signal. This seems to be the first known case of a frameshift which is used, along with the termination codon in the -1 frame, to terminate a peptide within a reading frame. [Mutagenesis of a dibasic peptide (lys-lys) at codons 498-499, the site at which a tau'-'LacZ fusion protein was cleaved in vitro (1) had no effect on gamma formation in vivo, suggesting that cleavage observed in vitro is not the mechanism of gamma formation in vivo.",,"['Blinkowa, A L', 'Walker, J R']",,,,
,PMC,Effect of deferoxamine pretreatment on acute pneumonic pasteurellosis and neutrophil oxidative metabolism in calves.,,PMC1255639,,,"Iron plays a central role in bacterial infections, influencing both bacterial virulence and host cellular defense mechanisms. We investigated whether iron chelation might be of benefit in the treatment of pneumonic pasteurellosis of calves. Neutrophils obtained from calves previously treated with the iron chelator, deferoxamine, were studied for their responses to latex and opsonized zymosan by luminol-enhanced chemiluminescence and to phorbol myristate acetate and opsonized zymosan by superoxide generation. Treatment with deferoxamine in vivo failed to influence these in vitro measures of neutrophil oxidative metabolism. Furthermore, iron depletion with deferoxamine failed to modify the pathophysiological derangements that occurred in calves following experimental induction of pneumonia by intratracheal inoculation with Pasteurella haemolytica. These data indicate that iron chelation using deferoxamine cannot be recommended as an adjunct to conventional therapy in the treatment of pneumonic pasteurellosis of cattle.",,"['Slocombe, R F', 'Watson, G L', 'Killingsworth, C R']",,,,
,PMC,Isolation of a previously undescribed rickettsia from an aborted bovine fetus.,,PMC267805,,,"A previously undescribed obligate intracellular bacterium was isolated from an aborted bovine fetus. The organism was resistant to penicillin, replicated within cytoplasmic vacuoles, exhibited structural characteristics compatible with the rickettsias, and shared antigenic determinants with Cowdria ruminantium.",,"['Dilbeck, P M', 'Evermann, J F', 'Crawford, T B', 'Ward, A C', 'Leathers, C W', 'Holland, C J', 'Mebus, C A', 'Logan, L L', 'Rurangirwa, F R', 'McGuire, T C']",,,,
,PMC,Structure and orientation of expressed bovine coronavirus hemagglutinin-esterase protein.,,PMC249325,,,"The sequence of the hemagglutinin-esterase (HE) gene for the Mebus strain of bovine coronavirus was obtained from cDNA clones, and its deduced product is a 47,700-kilodalton apoprotein of 424 amino acids. Expression of the HE protein in vitro in the presence of microsomes revealed N-terminal signal peptide cleavage and C-terminal anchorage but not disulfide-linked dimerization. Dimerization was observed only after expression in vivo, during which HE was also transported to the cell surface.",,"['Kienzle, T E', 'Abraham, S', 'Hogue, B G', 'Brian, D A']",,,,
,PMC,Intraluminal proteolytic activation plays an important role in replication of type 1 reovirus in the intestines of neonatal mice.,,PMC249324,,,"Oral inoculation of suckling mice with reovirus serotype 1 (strain Lang) results in the conversion of intact virions to intermediate subviral particles (ISVPs) in the intestinal lumen. Digestion of virus in vitro with chymotrypsin or trypsin reveals two distinct forms of ISVPs, while the predominant species of ISVPs found in the small intestinal lumen appears to be identical to the chymotrypsin product. The in vivo conversion of virions to ISVPs was blocked by pretreatment of mice with protease inhibitors, resulting in inefficient replication of reovirus in intestinal tissue. The early inhibition of viral replication in suckling mice pretreated with protease inhibitors was not observed when suckling mice were inoculated with ISVPs generated by in vitro digestion with either chymotrypsin or trypsin. However, replication was decreased during secondary rounds of replication in mice receiving repeated doses of protease inhibitors, suggesting that luminal proteolytic digestion is important in rendering progeny virions infectious in the gut.",,"['Bass, D M', 'Bodkin, D', 'Dambrauskas, R', 'Trier, J S', 'Fields, B N', 'Wolf, J L']",,,,
,PMC,Promoter for Sindbis virus RNA-dependent subgenomic RNA transcription.,,PMC249310,,,"Sindbis virus is a positive-strand RNA enveloped virus, a member of the Alphavirus genus of the Togaviridae family. Two species of mRNA are synthesized in cells infected with Sindbis virus; one, the 49S RNA, is the genomic RNA; the other, the 26S RNA, is a subgenomic RNA that is identical in sequence to the 3' one-third of the genomic RNA. Ou et al. (J.-H. Ou, C. M. Rice, L. Dalgarno, E. G. Strauss, and J. H. Strauss, Proc. Natl. Acad. Sci. USA 79:5235-5239, 1982) identified a highly conserved region 19 nucleotides upstream and 2 nucleotides downstream from the start of the 26S RNA and proposed that in the negative-strand template, these nucleotides compose the promoter for directing the synthesis of the subgenomic RNA. Defective interfering (DI) RNAs of Sindbis virus were used to test this proposal. A 227-nucleotide sequence encompassing 98 nucleotides upstream and 117 nucleotides downstream from the start site of the Sindbis virus subgenomic RNA was inserted into a DI genome. The DI RNA containing the insert was replicated and packaged in the presence of helper virus, and cells infected with these DI particles produced a subgenomic RNA of the size and sequence expected if the promoter was functional. The initiating nucleotide was identical to that used for Sindbis virus subgenomic mRNA synthesis. Deletion analysis showed that the minimal region required to detect transcription of a subgenomic RNA from the negative-strand template of a DI RNA was 18 or 19 nucleotides upstream and 5 nucleotides downstream from the start of the subgenomic RNA.",,"['Levis, R', 'Schlesinger, S', 'Huang, H V']",,,,
,PMC,Expression and secretion of the bovine coronavirus hemagglutinin-esterase glycoprotein by insect cells infected with recombinant baculoviruses.,,PMC249298,,,A cDNA fragment representing the hemagglutinin-esterase (HE) gene of bovine coronavirus (BCV) was inserted into the genome of Autographa californica nuclear polyhedrosis virus. Infection of insect cells with the recombinant virus resulted in the production of a 120-kilodalton disulfide-linked dimeric form of the BCV HE polypeptide. Deletion of the carboxy-terminal hydrophobic domain from the HE polypeptide resulted in secretion of a dimeric form of the truncated HE polypeptide. The acetylesterase activity of the BCV HE was detectable in insect cells expressing the BCV hemagglutinin and was inhibited by two monoclonal antibodies which also inhibit hemagglutination.,,"['Parker, M D', 'Yoo, D', 'Babiuk, L A']",,,,
,PMC,Translational frameshifting generates the gamma subunit of DNA polymerase III holoenzyme.,,PMC53720,,,"The dnaX gene (previously called dnaZX) of Escherichia coli has only one open reading frame for a 71-kDa polypeptide from which two distinct DNA polymerase III holoenzyme subunits, tau (71 kDa) and gamma (47 kDa), are produced. To determine how the gamma subunit is generated, we examined the influence of mutations in the dnaX gene on the pattern of tau and gamma production in overproducing cells. Important structural elements in dnaX mRNA include a stretch of six adenines (nucleotides 1425-1430), a stable hairpin structure (nucleotides 1437-1466), and a UGA stop codon in a -1 frame (nucleotides 1434-1436) between the stretch of adenines and the hairpin structure. Disruption of this stop codon generates a slightly larger gamma subunit, indicative of the use of a -1 stop codon farther downstream (nucleotides 1470-1472). These results suggest that a -1 frameshift during translation allows the use of this UGA codon to terminate translation of the gamma polypeptide. The amino acid composition, sequence, and mass spectra of a C-terminal peptide from mild digestion of the purified gamma protein with endoproteinase Lys-C confirms that this frameshift occurs at either of the two lysine codons in the region of the adenine stretch. Remarkable features of this frameshifting are its high frequency (i.e., about 80% in an overproducing cell) and the striking structural similarity to the frameshifting signal responsible for expression of the pol and pro genes in many retroviruses.",,"['Tsuchihashi, Z', 'Kornberg, A']",,,,
,PMC,Nucleotide sequence of the bovine enteric coronavirus BECV F15 mRNA 5 and mRNA 6 unique regions.,,PMC330465,,,,,"['Woloszyn, N', 'Boireau, P', 'Laporte, J']",,,,
,PMC,Early death after feline infectious peritonitis virus challenge due to recombinant vaccinia virus immunization.,,PMC249267,,,"The gene encoding the fusogenic spike protein of the coronavirus causing feline infectious peritonitis was recombined into the genome of vaccinia virus. The recombinant induced spike-protein-specific, in vitro neutralizing antibodies in mice. When kittens were immunized with the recombinant, low titers of neutralizing antibodies were obtained. After challenge with feline infectious peritonitis virus, these animals succumbed earlier than did the control group immunized with wild-type vaccinia virus (early death syndrome).",,"['Vennema, H', 'de Groot, R J', 'Harbour, D A', 'Dalderup, M', 'Gruffydd-Jones, T', 'Horzinek, M C', 'Spaan, W J']",,,,
,PMC,Fusion function of the Semliki Forest virus spike is activated by proteolytic cleavage of the envelope glycoprotein precursor p62.,,PMC249238,,,"The precursor protein p62 of the prototype alphavirus Semliki Forest virus (SFV) undergoes during transport to the cell surface a proteolytic cleavage to form the mature envelope glycoprotein E2. To investigate the biological significance of this cleavage event, single amino acid substitutions were introduced at the cleavages site through mutagenesis of cDNA corresponding to the structural region of the SFV genome. The phenotypes of the cleavage site mutants were studied in BHK cells by using recombinant vaccinia virus vectors. Nonconservative substitutions completely abolished p62 cleavage. Uncleaved p62 was transported with normal kinetics to the cell surface, where it became accessible to low concentrations of exogenous trypsin. The proteolytic cleavage of envelope glycoprotein precursors has been shown to activate the membrane fusion potential of viral spikes in several virus families. Here we demonstrate that the fusion function of the SFV spike is activated by the cleavage of p62. Cleavage-deficient p62 expressed at the cell surface did not function in low-pH-triggered (pH 5.5) cell-cell membrane fusion; however, cleavage of the mutated p62 with exogenous trypsin restored the fusion function. We discuss a model for SFV assembly and fusion where p62 cleavage plays a crucial role in the stability of the multimeric association of the viral envelope glycoproteins.",,"['Lobigs, M', 'Garoff, H']",,,,
,PMC,Coronavirus transcription: subgenomic mouse hepatitis virus replicative intermediates function in RNA synthesis.,,PMC249216,,,"Both genomic and subgenomic replicative intermediates (RIs) and replicative-form (RF) structures were found in 17CL1 mouse cells that had been infected with the A59 strain of mouse hepatitis virus (MHV), a prototypic coronavirus. Seven species of RNase-resistant RF RNAs, whose sizes were consistent with the fact that each was derived from an RI that was engaged in the synthesis of one of the seven MHV positive-strand RNAs, were produced by treatment with RNase A. Because the radiolabeling of the seven RF RNAs was proportional to that of the corresponding seven positive-strand RNAs, the relative rate of synthesis of each of the MHV positive-strand RNAs may be controlled by the relative number of each of the size classes of RIs that are produced. In contrast to alphavirus, which produced its subgenome-length RF RNAs from genome-length RIs, MHV RF RNAs were derived from genome- and subgenome-length RIs. Only the three largest MHV RF RNAs (RFI, RFII, and RFIII) were derived from the RIs that migrated slowest on agarose gels. The four smallest RF RNAs (RFIV, RFV, RFVI, and RFVII) were derived from RIs that migrated in a broad region of the gel that extended from the position of 28S rRNA to the position of the viral single-stranded MHV mRNA-3. Because all seven RIs were labeled during very short pulses with [3H]uridine, we concluded that the subgenome-length RIs are transcriptionally active. These findings, with the recent report of the presence of subgenome-length negative-strand RNAs in cells infected with porcine transmissible gastroenteritis virus (P. B. Sethna, S.-L. Hung, and D. A. Brian, Proc. Natl. Acad. Sci. USA 86: 5626-5630, 1989), strongly suggest that coronaviruses utilize a novel replication strategy that employs the synthesis of subgenomic negative strands to produce subgenomic mRNAs.",,"['Sawicki, S G', 'Sawicki, D L']",,,,
,PMC,Cytopathic astrovirus isolated from porcine acute gastroenteritis in an established cell line derived from porcine embryonic kidney.,,PMC269575,,,"A cytopathic astrovirus was isolated from pigs with acute diarrhea in an established cell line that was derived from porcine embryonic kidneys with the aid of trypsin. The virus showed a distinct cytopathic effect characterized by an enlargement of cells and the appearance of fine granules in the cytoplasm. Porcine astrovirus was shown to have an RNA genome, as determined by the effect of 5-iodo-2'-deoxyuridine on its replication, and five polypeptides with molecular masses of 13,000, 30,000, 31,000, 36,000, and 39,000 daltons; and it was shown to be stable to lipid solvents and heating at 50 degrees C for 30 min but somewhat labile to acid (pH 3.0). The buoyant density of the isolate determined in CsCl was 1.35 g/ml. Seroconversion to the virus was evident in the paired serum specimens obtained from pigs with diarrhea that were housed at the farm where the disease occurred. The neutralization test on serum specimens collected randomly from 128 adult pigs of eight herds revealed that 50 of the serum specimens were positive for antibody to porcine astrovirus, although there was considerable variation in the prevalence among herds, ranging from 0 to 83%. Hysterectomy-produced, colostrum-deprived, 4-day-old pigs developed mild diarrhea after oral exposure to porcine astrovirus propagated in the cell culture; and the virus was isolated again from diarrheal stool specimens.",,"['Shimizu, M', 'Shirai, J', 'Narita, M', 'Yamane, T']",,,,
,PMC,Foot-and-mouth disease virus protease 3C induces specific proteolytic cleavage of host cell histone H3.,,PMC249169,,,"In foot-and-mouth disease virus (FMDV)-infected cells, the disappearance of nuclear protein histone H3 and the simultaneous appearance of a new chromatin-associated protein termed Pi can be observed (P. R. Grigera and S. G. Tisminetzky, Virology 136:10-19, 1984). We sequenced the amino terminus of protein Pi and showed that Pi derives from histone H3 by proteolytic cleavage. The 20 N-terminal amino acid residues of histone H3 are specifically cleaved off early during infection. Truncated histone H3 remains chromatin associated. In addition, we showed that the histone H3-Pi transition is catalyzed by the FMDV 3C protease. The only known function of the viral 3C protease was, until now, the processing of the viral polyprotein. The viral 3C protease is the only FMDV protein required to induce the histone H3-Pi transition, as well as being the only viral protein capable of cleaving histone H3. No viral precursor fusion protein is needed for this specific cleavage as was reported for the processing of the poliovirus P1 precursor polyprotein by 3C/D protease. As the deleted part of the histone H3 corresponds to the presumed regulatory domain involved in the regulation of transcriptionally active chromatin in eucaryotes, it seems possible that this specific cleavage of histone H3 is related to the host cell transcription shutoff reported for several picornaviruses.",,"['Falk, M M', 'Grigera, P R', 'Bergmann, I E', 'Zibert, A', 'Multhaup, G', 'Beck, E']",,,,
,PMC,Neutralization-resistant variants of a neurotropic coronavirus are generated by deletions within the amino-terminal half of the spike glycoprotein.,,PMC249167,,,"Neuroattenuated variants of mouse hepatitis virus type 4 (MHV-4) selected for resistance to neutralizing monoclonal antibodies (R.G. Dalziel, P.W. Lampert, P. J. Talbot, and M. J. Buchmeier, J. Virol. 59:463-471, 1986) were found to harbor large deletions in both mRNA 3 and its protein product, the 180-kilodalton viron spike (S) glycoprotein. By using antipeptide antibodies directed against selected portions of the chain, deletions were mapped to the middle of the amino-terminal S1 fragment, one of the two posttranslational cleavage products of S, and involved omission of 15 kilodaltons of protein. Deletion mutants could be selected only after multiple passage of virus through cultured cell lines; minimally passaged MHV-4 stocks contained putative point mutants selectable by neutralizing monoclonal antibodies but no deletions. Enhanced growth of deletion mutants relative to wild-type virus was observed in four cell lines used for virus propagation and was attributed to delayed and diminished cytopathic effects that allowed cultures to support virus production for prolonged periods. This hypothesis was reinforced by the finding that no selective advantage for the deletion mutants was observed in two cell lines resistant to virus-induced cytopathic effects. These results indicate that the passaging of MHV-4 in culture generates heterogeneity in S structure and eventually selects for rare neutralization-resistant deletion mutants with decreased virulence properties.",,"['Gallagher, T M', 'Parker, S E', 'Buchmeier, M J']",,,,
,PMC,Antibody-induced restriction of viral gene expression in measles encephalitis in rats.,,PMC249164,,,"After infection with the neurotropic CAM/RBH measles virus (MV) strain, newborn Lewis rats succumb to an acute necrotizing encephalopathy. Passive transfer of neutralizing monoclonal antibodies directed against MV hemagglutinin prevented this disease process. Instead, either an antibody-induced acute or subacute measles encephalitis developed after a prolonged incubation period with a restricted expression of MV structural proteins. The molecular biological analysis of MV gene expression in brain tissue of rats treated with MV-neutralizing antibodies revealed a transcriptional restriction of viral mRNAs, particularly for the envelope proteins, leading to a steep expression gradient. Based on in situ hybridization, it was concluded that the efficiency of transcription of viral genes at the single-cell level is reduced compared with that of controls. Passive immunization with monoclonal antibodies directed against other MV structural proteins proved to be ineffective. Similar results were obtained in MV-infected weanling Brown Norway rats. These rats developed a clinically silent encephalitis in the presence of high titers of neutralizing antibodies. In such animals, a pronounced attenuation of the viral gene transcription was observed. These findings indicated that neutralizing antibodies directed against a restricted set of specific antigenic sites on the viral hemagglutinin protein expressed on cell membranes exert a modulating effect on the viral gene expression at the level of transcription. This phenomenon contributes to the switch from the acute cytopathic effect to a persistent infection in the central nervous system.",,"['Liebert, U G', 'Schneider-Schaulies, S', 'Baczko, K', 'ter Meulen, V']",,,,
,PMC,Identification of a locus on mouse chromosome 3 involved in differential susceptibility to Theiler's murine encephalomyelitis virus-induced demyelinating disease.,,PMC249161,,,"Theiler's virus-induced demyelinating disease results from a chronic infection in the white matter of the central nervous system and provides an excellent model for human multiple sclerosis. Like multiple sclerosis, there are genetic risk factors in disease development, including genes associated with the major histocompatibility complex and with those encoding the beta chain of the T-cell receptor. Comparisons of the susceptible DBA/2 and resistant C57BL/6 strains have indicated an important role for the H-2D locus and for a non-H-2 gene (not involving the beta chain of the T-cell receptor) in differential susceptibility. In the present report, analysis of recombinant-inbred strains (BXD) between the DBA/2 and C57BL/6 strains indicated that this non-H-2 locus is located at the centromeric end of chromosome 3 near (4 +/- 4 centimorgans) the carbonic anhydrase-2 (Car-2) enzyme locus.",,"['Melvold, R W', 'Jokinen, D M', 'Miller, S D', 'Dal Canto, M C', 'Lipton, H L']",,,,
,PMC,Feline leukemia virus infection as a potentiating cofactor for the primary and secondary stages of experimentally induced feline immunodeficiency virus infection.,,PMC249149,,,"Preexistent feline leukemia virus (FeLV) infection greatly potentiated the severity of the transient primary and chronic secondary stages of feline immunodeficiency virus (FIV) infection. Of 10 FeLV-FIV carrier cats, 5 died of experimentally induced FIV infection, compared with 2 deaths in 10 cats infected only with FeLV and 1 death in 7 cats infected only with FIV. FIV-infected cats with preexistent FeLV infections developed severe depression, anorexia, fever, diarrhea, dehydration, weight loss, and leukopenia 4 to 6 weeks after infection and were moribund within 2 weeks of the onset of signs, whereas cats infected only with FIV developed much milder self-limiting gross and hematologic abnormalities. Pathologic findings in dually infected cats that died were similar to those observed previously in cats dying from uncomplicated primary FIV infection but were much more widespread and severe. Coinfection of asymptomatic FeLV carrier cats with FIV did not increase the levels of FeLV p27 antigen present in their blood over that seen in cats infected with FeLV alone. The amount of proviral FIV DNA was much higher, however, in dually infected cats than in cats infected only with FIV; there was a greater expression of FIV DNA in lymphoid tissues, where the genome was normally detected, and in nonlymphoid tissues, where FIV DNA was not usually found. Dually infedted cats that recovered from the primary stage of FIV infection remained more leukopenic than cats infected with FIV or FeLV alone, and their CD4+/CD8+ T-lymphocyte ratios were inverted. One of these cats developed what was considered to be an opportunistic infection. It was concluded, therefore, that a preexistent FeLV infection in some way enhanced the expression and spread of FIV in the body and increased the severity of both the resulting transient primary and chronic secondary stages of FIV infection. This study also demonstrated the usefulness of the FIV model in studying the role of incidental infectious diseases as cofactors for immunodeficiency-causing lentiviruses.",,"['Pedersen, N C', 'Torten, M', 'Rideout, B', 'Sparger, E', 'Tonachini, T', 'Luciw, P A', 'Ackley, C', 'Levy, N', 'Yamamoto, J']",,,,
,PMC,Specificities involved in the initiation of retroviral plus-strand DNA.,,PMC249148,,,"Reverse transcription of the retroviral RNA genome begins with tRNA-primed synthesis of a minus-strand DNA, which subsequently acts as the template for the synthesis of plus-strand DNA. This plus-strand DNA is initiated at a unique location and makes use of a purine-rich RNA oligonucleotide derived by RNase H action on the viral RNA. To determine the variables that are relevant to successful specific initiation of plus-strand DNA synthesis, we have used nucleic acid sequences from the genome of Rous sarcoma virus along with three different sources of RNase H: avian myeloblastosis virus DNA polymerase, murine leukemia virus DNA polymerase, and the RNase H of Escherichia coli. Our findings include evidence that specificity is controlled not only by the nucleic acid sequences but also by the RNase H. For example, while the avian reverse transcriptase efficiently and specifically initiates on the sequences of the avian retrovirus, the murine reverse transcriptase initiates specifically but at a location 4 bases upstream of the correct site.",,"['Luo, G X', 'Sharmeen, L', 'Taylor, J']",,,,
,PMC,A rabbit model for mucosal immunity in the bowel. II. Local cellular reactivity to virus infection.,,PMC1385715,,,"An animal model was used to examine local and systemic cellular reactivity against virus infection of bowel mucosa. Firstly, existing techniques for extracting lymphoid cells from the dispersed populations of the bowel mucosa were adapted for use in rabbits and viable lymphocytes were isolated from the lapine ileal mucosa in numbers suitable for assay. Lamina propria lymphocytes (LPL) showed a strong blastogenic response to T-cell mitogens but intra-epithelial lymphocytes (IEL) responded poorly, even in the presence of splenic accessory cells. Next, chronically isolated ileal loops in rabbits were infected with parainfluenzavirus type 3 (PI-3) and isolates from the organized and dispersed lymphoid tissues associated with infected ileal mucosae and those from systemic lymphoid sites were used in in vitro assays of virus-specific lympho-proliferation. A T-cell-mediated immune response against PI-3 was mounted in lymphoid tissues associated with the infected loops, appearing first in loop Peyer's patches (PP) at Day 4 and in mesenteric lymph nodes (MLN) and lamina propriae at Day 7 after infection. The response in PP had waned by 21 days but was sustained in the other sites for at least 42 days. Epithelial lymphocytes were consistently anergic and there was no evidence of specific reactivity at systemic lymphoid sites or elsewhere in the bowel. Thus, a highly localized T-cell-mediated response was sustained, not only in organized lymphoid tissues but also in the bowel wall itself, following infection with a novel antigen.",,"['Ramsay, A J', 'Holmes, M J']",,,,
,PMC,Glycoprotein glycans that inhibit adhesion of Escherichia coli mediated by K99 fimbriae: treatment of experimental colibacillosis.,,PMC258414,,,"Calf diarrhea due to infection by enterotoxigenic Escherichia coli was treated by administration of glycoprotein glycans derived from bovine plasma. The glycan moieties of the nonimmunoglobulin fraction of plasma mimicked the oligosaccharide moiety of intestinal receptors recognized by K99 pili. These glycoprotein glycans inhibited adhesion of E. coli K99+ ST+ to erythrocyte glycoconjugates in vitro, and they protected colostrum-deprived newborn calves against lethal doses of enterotoxigenic E. coli (10(10) bacteria). Adhesion of bacteria to the intestines (duodenum, jejunum, and ileum) was significantly reduced (by 2 orders of magnitude) in treated calves.",,"['Mouricout, M', 'Petit, J M', 'Carias, J R', 'Julien, R']",,,,
,PMC,Intracellular transport of recombinant coronavirus spike proteins: implications for virus assembly.,,PMC249107,,,"Coronavirus spike protein genes were expressed in vitro by using the recombinant vaccinia virus expression system. Recombinant spike proteins were expressed at the cell surface and induced cell fusion in a host-cell-dependent fashion. The intracellular transport of recombinant spike proteins was studied. The half time of acquisition of resistance to endo-beta-N-acetylglucosaminidase H was approximately 3 h for the recombinant feline infectious peritonitis virus S protein. The S protein in feline infectious peritonitis virus-infected cells was found to have a half time of acquisition of resistance to endo-beta-N-acetylglucosaminidase H of approximately 1 h. This difference can be explained by the fact that coronavirus budding takes place at intracellular membranes and that the oligosaccharides of the spike protein are modified after budding. Apparently, spike protein incorporated into budded virions is transported faster through the Golgi apparatus than is spike protein alone. These findings provide new insights into the mechanism of coronavirus budding and are discussed in relation to current models of intracellular transport and sorting of proteins.",,"['Vennema, H', 'Heijnen, L', 'Zijderveld, A', 'Horzinek, M C', 'Spaan, W J']",,,,
,PMC,A 3'-coterminal nested set of independently transcribed mRNAs is generated during Berne virus replication.,,PMC249106,,,"By using poly(A)-selected RNA from Berne virus (BEV)-infected embryonic mule skin cells as a template, cDNA was prepared and cloned in plasmid pUC9. Recombinants covering a contiguous sequence of about 10 kilobases were identified. Northern (RNA) blot hybridizations with various restriction fragments from these clones showed that the five BEV mRNAs formed a 3'-coterminal nested set. Sequence analysis revealed the presence of four complete open reading frames of 4743, 699, 426, and 480 nucleotides, with initiation codons coinciding with the 5' ends of BEV RNAs 2 through 5, respectively. By using primer extension analysis and oligonucleotide hybridizations, RNA 5 was found to be contiguous on the consensus sequence. The transcription of BEV mRNAs was studied by means of UV mapping. BEV RNAs 1, 2, and 3 were shown to be transcribed independently, which is also likely--although not rigorously proven--for RNAs 4 and 5. Upstream of the AUG codon of each open reading frame a conserved sequence pattern was observed which is postulated to function as a core promoter sequence in subgenomic RNA transcription. In the area surrounding the core promoter region of the two most abundant subgenomic BEV RNAs, a number of homologous sequence motifs were identified.",,"['Snijder, E J', 'Horzinek, M C', 'Spaan, W J']",,,,
,PMC,"Space-time clustering of, and risk factors for, farmer-diagnosed winter dysentery in dairy cattle",,PMC1681324,,,"We used two statistical techniques for space-time cluster analysis, the Knox and the Mantel regression methods, for an analysis of whether herd outbreaks of farmer-diagnosed winter dysentery during the winter of 1987-1988 were clustered in space and time more than would be expected by chance. Using the Knox method, there was significant space-time clustering of outbreaks of winter dysentery within a 30 day time and a 5.5 km radius. There was also significant space-time clustering by the Mantel regression method. Logistic regression was used to study risk factors for herd outbreaks of winter dysentery. Large herds (>60 cows) and herds with a history of an outbreak prior to 1987 had increased chances of an outbreak occurring in 1987-1988. These results are compatible with an infectious cause for winter dysentery.",,"['White, Maurice E.', 'Schukken, Ynte Hein', 'Tanksley, Beth']",,,,
,PMC,The time course of the humoral immune response to rhinovirus infection.,,PMC2249538,,,"The specific humoral immune response of 17 volunteers to infection with human rhinovirus type 2 (HRV-2) has been measured both by neutralization and by ELISA. Six volunteers who had HRV-2-specific antibodies in either serum or nasal secretions before HRV-2 inoculation were resistant to infection and illness. Of the remaining 11 volunteers who had little pre-existing HRV-2-specific antibody, one was immune but 10 became infected and displayed increases in HRV-2-specific antibodies. These antibodies first increased 1-2 weeks after infection and reached a maximum at 5 weeks. All six resistant volunteers who had high pre-existing antibody and eight of the volunteers who became infected maintained their HRV-2-specific antibody for at least 1 year. At this time they were protected against reinfection. Two volunteers showed decreases in HRV-2-specific antibodies from either serum or nasal secretions. They became infected but not ill after HRV-2 inoculation 1 year later.",,"['Barclay, W. S.', 'al-Nakib, W.', 'Higgins, P. G.', 'Tyrrell, D. A.']",,,,
,PMC,Infection of peritoneal macrophages in vitro and in vivo with feline immunodeficiency virus.,,PMC251221,,,"Macrophages were harvested from the peritoneal cavities of healthy specific-pathogen-free cats by saline lavage. Three days before collection, the peritoneal cavities were stimulated with glutaraldehyde-fixed Saccharomyces cerevisiae cells to induce greater numbers of macrophages and to begin the activation sequence. Peritoneal macrophages from cats stimulated once with yeast consisted mainly of small macrophages and a smaller number of larger activated macrophages. After several days in culture, many of the small macrophages became activated and a portion of the activated macrophages developed into multinucleated giant cells. Peritoneal cells from cats that were stimulated twice or three times with yeast at 3-week intervals consisted of a higher proportion of activated macrophages initially and produced more and larger multinuclear giant cells with time. Cultures of peritoneal cells stimulated once with yeast were easily infected in vitro with feline immunodeficiency virus (FIV) and produced a transient burst of reverse transcriptase activity. After the initial burst of virus replication, the infection became latent. Even more multinucleated giant cells appeared after infection, and many of these cells fused with each other. Replicating virus could be rescued from the latently infected macrophages after 2 to 3 weeks of phorbol myristate acetate stimulation and cocultivation with T-lymphocyte-enriched peripheral blood mononuclear cells. Multiply stimulated peritoneal cells, which contained a much higher proportion of activated macrophages, could also be infected in vitro with FIV. The infection usually became latent, however, without going through an initial replicative stage. Peritoneal cells from chronically FIV-infected specific-pathogen-free cats contained a higher proportion of activated macrophages and were latently infected with FIV from the outset.",,"['Brunner, D', 'Pedersen, N C']",,,,
,PMC,Evidence for specificity in the encapsidation of Sindbis virus RNAs.,,PMC251197,,,"We investigated the interaction of the capsid protein of Sindbis virus with Sindbis viral RNAs and defined a region of the genome that is required for binding in vitro and for packaging in vivo. The binding studies were performed with purified capsid protein immobilized on nitrocellulose and 32P-labeled RNAs transcribed in vitro from viral and nonspecific cDNAs. Genomic and defective interfering (DI) RNAs bound capsid protein significantly better than either the subgenomic (26S) RNA or nonspecific RNAs. Transcripts prepared from either truncated or deleted cDNAs were used to define the segment required for binding. This segment, which is represented twice in DI RNA, lies between nucleotides 746 and 1226 of the genomic RNA and is within the coding region of the nonstructural protein nsP1. Insertion of a domain covering these sequences into a nonviral RNA was able to convert it from a background level of binding to an activity that was 80% that of the Sindbis virus DI RNA. We analyzed DI RNA transcripts in detail because they could be studied not only for the ability to bind capsid protein in vitro but also for the ability to be replicated and packaged in vivo in the presence of helper virion RNA. The results obtained with three DI RNAs are reported. One (CTS14), which has one copy of the binding domain, bound efficiently to capsid protein in vitro and was packaged in vivo as measured by amplification on passaging. In contrast, a DI RNA (CTS1) which lacked this region did not bind to capsid protein and was not detected on passaging. By using lipofectin (P. L. Felgner, T. R. Gadek, M. Holm, R. Roman, H. W. Chan, M. Wenz, J.P. Northrop, G. M. Ringold, and M. Danielson, Proc. Natl. Acad. Sci. USA 84:7413-7417, 1987) to enhance RNA uptake, we were able to demonstrate that CTS1 RNA was replicated in the transfected cells. It was replicated to the same level as another DI RNA (CTS253) which has only the 3' 279 nucleotides of the binding domain and these are located near the 3' terminus of the RNA. CTS253 bound capsid protein to an intermediate level but was amplified on passaging. The binding studies and the in vivo packaging data, taken together, provide strong support for the conclusion that there is a specific capsid recognition domain in Sindbis virus RNA that plays a role in nucleocapsid assembly.",,"['Weiss, B', 'Nitschko, H', 'Ghattas, I', 'Wright, R', 'Schlesinger, S']",,,,
,PMC,High-frequency leader sequence switching during coronavirus defective interfering RNA replication.,,PMC251194,,,"A system was developed that exploited defective interfering (DI) RNAs of coronavirus to study the role of free leader RNA in RNA replication. A cDNA copy of mouse hepatitis virus DI RNA was placed downstream of the T7 RNA polymerase promoter to generate DI RNAs capable of extremely efficient replication in the presence of a helper virus. We demonstrated that, in the DI RNA-transfected cells, the leader sequence of these DI RNAs was switched to that of the helper virus during one round of replication. This high-frequency leader sequence exchange was not observed if a nine-nucleotide stretch of sequence (UUUAUAAAC) at the junction between the leader and the remaining DI sequence was deleted. This observation suggests that a free leader RNA generated from the genomic RNA of mouse hepatitis virus may participate in the replication of DI RNA.",,"['Makino, S', 'Lai, M M']",,,,
,PMC,La Crosse virus nucleocapsid protein controls its own synthesis in mosquito cells by encapsidating its mRNA.,,PMC251180,,,"Within 24 to 48 h of La Crosse virus infection of mosquito cells, greater than 75% of the S mRNA was found to band in CsCl density gradients at the position of genome or antigenome nucleocapsids. The encapsidation of the S mRNA correlates with the repression of N protein synthesis in vivo, and the encapsidated S mRNA cannot be translated in vitro. Unlike genome and antigenome assembly, S mRNA assembly is a relatively slow process, which is not coupled to its synthesis. Within the encapsidated S mRNA population, three forms could be distinguished, those with intact primers which were or were not also assembled with N protein and those in which the primer and up to 3 template bases had been lost. We suggest that genome replication, but not transcription, is down regulated with time in mosquito cells for reasons that are unclear. The pool of unassembled N protein then increased to the point at which it began to interact with its own mRNA, as this mRNA also contains what is considered to be the assembly site, i.e., the conserved sequences at the 5' ends of all genome and antigenome chains. This lead to the assembly of the entire mRNA, except for the nontemplate primer. Some of the primers were then also assembled with N protein, whereas others were digested to produce truncated mRNAs.",,"['Hacker, D', 'Raju, R', 'Kolakofsky, D']",,,,
,PMC,Rotavirus gene structure and function.,,PMC372748,,,"Knowledge of the structure and function of the genes and proteins of the rotaviruses has expanded rapidly. Information obtained in the last 5 years has revealed unexpected and unique molecular properties of rotavirus proteins of general interest to virologists, biochemists, and cell biologists. Rotaviruses share some features of replication with reoviruses, yet antigenic and molecular properties of the outer capsid proteins, VP4 (a protein whose cleavage is required for infectivity, possibly by mediating fusion with the cell membrane) and VP7 (a glycoprotein), show more similarities with those of other viruses such as the orthomyxoviruses, paramyxoviruses, and alphaviruses. Rotavirus morphogenesis is a unique process, during which immature subviral particles bud through the membrane of the endoplasmic reticulum (ER). During this process, transiently enveloped particles form, the outer capsid proteins are assembled onto particles, and mature particles accumulate in the lumen of the ER. Two ER-specific viral glycoproteins are involved in virus maturation, and these glycoproteins have been shown to be useful models for studying protein targeting and retention in the ER and for studying mechanisms of virus budding. New ideas and approaches to understanding how each gene functions to replicate and assemble the segmented viral genome have emerged from knowledge of the primary structure of rotavirus genes and their proteins and from knowledge of the properties of domains on individual proteins. Localization of type-specific and cross-reactive neutralizing epitopes on the outer capsid proteins is becoming increasingly useful in dissecting the protective immune response, including evaluation of vaccine trials, with the practical possibility of enhancing the production of new, more effective vaccines. Finally, future analyses with recently characterized immunologic and gene probes and new animal models can be expected to provide a basic understanding of what regulates the primary interactions of these viruses with the gastrointestinal tract and the subsequent responses of infected hosts.",,"['Estes, M K', 'Cohen, J']",,,,
,PMC,Expression of dicistronic transcriptional units in transgenic tobacco.,,PMC363739,,,"We investigated whether the two cistrons of a dicistronic mRNA can be translated in plants to yield both gene products. The coding sequences of various reporter genes were combined in dicistronic units, and their expression was analyzed in stably transformed tobacco plants at the RNA and protein levels. The presence of an upstream cistron resulted in all cases in a drastically reduced expression of the downstream cistron. The translational efficiency of the gene located downstream in the dicistronic units was 500- to 1,500-fold lower than that in a monocistronic control; a 500-fold lower value was obtained with a dicistronic unit in which both cistrons were separated by 30 nucleotides, whereas a 1,500-fold lower value was obtained with a dicistronic unit in which the stop codon of the upstream cistron and the start codon of the downstream cistron overlapped. As a strategy to select indirectly for transformants with enhanced levels of expression of a gene which is by itself nonselectable, the gene of interest can be cloned upstream from a selectable marker in a dicistronic configuration. This strategy can be used provided that the amount of dicistronic mRNA is high. If, on the other hand, the expression of the dicistronic unit is too low, selection of the downstream cistron will primarily give clones with rearranged dicistronic units.",,"['Angenon, G', 'Uotila, J', 'Kurkela, S A', 'Teeri, T H', 'Botterman, J', 'Van Montagu, M', 'Depicker, A']",,,,
,PMC,Human cryptosporidiosis associated with an epizootic in calves.,,PMC1349807,,,"An outbreak of human cryptosporidiosis occurred among previously healthy persons in a veterinary medical teaching hospital. Human illness began after admission of calves from a farm which had been experiencing an epizootic of neonatal diarrhea due to Cryptosporidium. The clinical syndrome in humans was characterized by watery diarrhea, abdominal cramping, flatulence, and headache. Cryptosporidiosis was confirmed by zinc sulfate flotation of fecal specimens in four persons, three of whom had been responsible for the care and treatment of infected calves. A fourth patient had washed her husband's soiled clothing and appeared to have been infected indirectly through fomite contamination. Among 112 persons surveyed, 26 (23.2 percent) had a diarrheal illness during the outbreak and nine met the case definition of a diarrheal illness lasting at least three days. These persons were more likely to have had contact with a calf with diarrhea than were 52 referents who did not become ill during the outbreak.",,"['Reif, J S', 'Wimmer, L', 'Smith, J A', 'Dargatz, D A', 'Cheney, J M']",,,,
,PMC,Viruses and virus-like particles detected during examination of feces from calves and piglets with diarrhea,,PMC1681319,,,"A total of 763 fecal or intestinal samples from diarrheic calves and piglets were examined for viral content by immunofluorescence, electron microscopy or cell culture. Routine fluorescent antibody and cultural tests detected rotavirus (n=126), coronavirus (n=80) and bovine viral diarrhea virus (n=13). Electron microscopy detected rotaviruses (n=24) and coronaviruses (n=17) not identified by standard fluorescent antibody tests. Other viruses detected by electron microscopy included Breda virus-like particles (n=49), astroviruses (n=1), caliciviruses (n=1), rhabdoviruses (n=1), parvoviruses (n=2), enteroviruses (n=3), togavirus-like particles (n=2), and “chained” particles (n=5). Mixtures of several of the viruses were detected in a number of fecal samples. The survey emphasized the value of electron microscopy as a broad-spectrum diagnostic tool.",,"['Durham, Peter J.K.', 'Hassard, Lori E.', 'Norman, G.R. (Bob)', 'Yemen, Roberta L.']",,,,
,PMC,Expression of tetanus toxin subfragments in vitro and characterization of epitopes.,,PMC259859,,,"To define epitopes of tetanus toxin, we compared four different in vitro systems in terms of their ability to produce tetanus toxin-specific subfragments from cloned DNA. A transcription-translation system developed from a nontoxigenic strain of Clostridium tetani was found to yield predominantly full-sized peptides. Such peptides were used to map six different epitopes for eight monoclonal antibodies. The toxin-neutralizing properties of the antibodies were determined in an in vitro assay, based on the toxin-mediated inhibition of norepinephrine release from rat brain particles. Two monoclonal antibodies recognizing epitopes within the regions Ser-744 to Ser-864 and Ile-1224 to Asp-1315 could neutralize the toxin. A third nonneutralizing antibody was shown to recognize the synthetic peptide Phe-947 to Glu-967 derived from the tetanus toxin sequence. This peptide contains a human T-cell epitope.",,"['Andersen-Beckh, B', 'Binz, T', 'Kurazono, H', 'Mayer, T', 'Eisel, U', 'Niemann, H']",,,,
,PMC,Detection of infectious bursal disease viruses by using cloned cDNA probes.,,PMC267053,,,"A molecular clone representing 445 base pairs at the 3' end of infectious bursal disease virus (IBDV) genome segment B was used in a dot blot hybridization assay to detect viral RNA from cell culture and from chicken bursa and spleen tissue specimens. The cloned nucleotide sequence represents approximately 14% of the virus-encoded polymerase (VP-1) gene. The lower detection limit of radiolabeled probes prepared from this clone was 0.1 ng of IBDV double-stranded RNA. The probe had broad specificity and was used to detect four serotype 1 IBDV strains and one serotype 2 IBDV strain. This probe, however, did not cross-react with nucleic acid extracted from nine unrelated poultry viruses. A rapid procedure for isolation of IBDV genomic RNA from bursa and spleen tissue specimens was developed and used with the dot blot hybridization assay to detect IBDV strains in tissue samples from experimentally infected and commercially reared chickens.",,"['Jackwood, D J', 'Kibenge, F S', 'Mercado, C C']",,,,
,PMC,"The reovirus M1 gene, encoding a viral core protein, is associated with the myocarditic phenotype of a reovirus variant.",,PMC251123,,,"Reoviruses contain a genome composed of 10 double-stranded RNA gene segments. A reovirus reassortant, 8B, derived from type 1 Lang (T1L) and type 3 Dearing (T3D), displayed a phenotype unlike that of either of its parents in that it efficiently induced numerous macroscopic external cardiac lesions in neonatal mice (B. Sherry, F. J. Schoen, E. Wenske, and B. N. Fields, J. Virol. 63:4840-4849, 1989). A panel of T1L/T3D reassortants and a panel of reassortants derived from 8B were used to determine whether novel T1L/T3D gene associations in 8B were responsible for its myocarditic phenotype. The results eliminated the possibility that any T1L/T3D gene combination found in 8B, from 2 genes to all 10 genes, was the explanation for its induction of cardiac lesions. This suggested that a mutation(s) in an 8B gene(s) might be responsible for induction of the myocarditis. Statistical analysis of experiments with 31 reassortants derived from 8B revealed a highly significant association (P = 0.002) of the 8B M1 gene with induction of cardiac lesions. The reovirus M1 gene encodes a viral core protein of unknown function, although evidence suggests a potential role in core structure and/or viral RNA synthesis. This represents the first report of the association of a viral gene with induction of myocarditis.",,"['Sherry, B', 'Fields, B N']",,,,
,PMC,A recombinant hepatitis B core antigen polypeptide with the protamine-like domain deleted self-assembles into capsid particles but fails to bind nucleic acids.,,PMC251098,,,"We have cloned in Escherichia coli both the complete core gene of hepatitis B virus and a truncated version of it, leading to the synthesis of high levels of a core-antigen-equivalent polypeptide (r-p22) and of an e-antigen-equivalent polypeptide (r-p16), respectively. We then compared the structural and antigenic properties of the two polypeptides, as well as their ability to bind viral nucleic acids. r-p16 was found to self-assemble into capsid-like particles that appeared similar, when observed under the electron microscope, to those formed by r-p22. In r-p16 particles, disulfide bonds linked the truncated polypeptides in dimers, assembled in the particle by noncovalent interactions. In r-p22 capsids, further disulfide bonds, conceivably involving the carboxy-terminal cysteines of r-p22 polypeptides, joined the dimers together, converting the structure into a covalently closed lattice. The protamine-like domain was at least partly exposed on the surface of r-p22 particles, since it was accessible to selective proteolysis. Finally, r-p22, but not r-p16, was shown to bind native and denatured DNA as well as RNA. Taken together, these results suggest that the protamine-like domain in core polypeptides is a nucleic acid-binding domain and is dispensable for the correct folding and assembly of amino-terminal and central regions.",,"['Gallina, A', 'Bonelli, F', 'Zentilin, L', 'Rindi, G', 'Muttini, M', 'Milanesi, G']",,,,
,PMC,Receptor activity of rotavirus nonstructural glycoprotein NS28.,,PMC251088,,,"Rotavirus morphogenesis involves the budding of subviral particles through the rough endoplasmic reticulum (RER) membrane of infected cells. During this process, particles acquire the outer capsid proteins and a transient envelope. Previous immunocytochemical and biochemical studies have suggested that a rotavirus nonstructural glycoprotein, NS28, encoded by genome segment 10, is a transmembrane RER protein and that about 10,000 Mr of its carboxy terminus is exposed on the cytoplasmic side of the RER. We have used in vitro binding experiments to examine whether NS28 serves as a receptor that binds subviral particles and mediates the budding process. Specific binding was observed between purified simian rotavirus SA11 single-shelled particles and RER membranes from SA11-infected monkey kidney cells and from SA11 gene 10 baculovirus recombinant-infected insect cells. Membranes from insect cells synthesizing VP1, VP4, NS53, VP6, VP7, or NS26 did not possess binding activity. Comparison of the binding of single-shelled particles to microsomes from infected monkey kidney cells and from insect cells indicated that a membrane-associated component(s) from SA11-infected monkey kidney cells interfered with binding. Direct evidence showing the interaction of NS28 and its nonglycosylated 20,000-Mr precursor expressed in rabbit reticulocyte lysates and single-shelled particles was obtained by cosedimentation of preformed receptor-ligand complexes through sucrose gradients. The domain on NS28 responsible for binding also was characterized. Reduced binding of single-shelled particles to membranes was seen with membranes treated with (i) a monoclonal antibody previously shown to interact with the C terminus of NS28, (ii) proteases known to cleave the C terminus of NS28, and (iii) the Enzymobead reagent. VP6 on single-shelled particles was suggested to interact with NS28 because (i) a monoclonal antibody to the subgroup I epitope on VP6 reduced particle binding, (ii) a purified polyclonal antiserum raised against recombinant baculovirus-produced VP6 reduced ligand binding, and (iii) a monoclonal antibody to a conserved epitope on VP6 augmented ligand binding. These experimental data provide support for the hypothesized receptor role of NS28 before the budding stage of rotavirus morphogenesis.",,"['Au, K S', 'Chan, W K', 'Burns, J W', 'Estes, M K']",,,,
,PMC,Circumstances and mechanisms of inhibition of translation by secondary structure in eucaryotic mRNAs.,,PMC363665,,,"This paper describes in vitro experiments with two types of intramolecular duplex structures that inhibit translation in cis by preventing the formation of an initiation complex or by causing the complex to be abortive. One stem-loop structure (delta G = -30 kcal/mol) prevented mRNA from engaging 40S subunits when the hairpin occurred 12 nucleotides (nt) from the cap but had no deleterious effect when it was repositioned 52 nt from the cap. This result confirms prior in vivo evidence that the 40S subunit-factor complex, once bound to mRNA, has considerable ability to penetrate secondary structure. Consequently, translation is most sensitive to secondary structure at the entry site for ribosomes, i.e., the 5' end of the mRNA. The second stem-loop structure (hp7; delta G = -61 kcal/mol, located 72 nt from the cap) was too stable to be unwound by 40S ribosomes, hp7 did not prevent a 40S ribosomal subunit from binding but caused the 40S subunit to stall on the 5' side of the hairpin, exactly as the scanning model predicts. Control experiments revealed that 80S elongating ribosomes could disrupt duplex structures, such as hp7, that were too stable to be penetrated by the scanning 40S ribosome-factor complex. A third type of base-paired structure shown to inhibit translation in vivo involves a long-range interaction between the 5' and 3' noncoding sequences.",,"Kozak, M",,,,
,PMC,The effects of feeding milk to diarrheic calves supplemented with oral electrolytes.,,PMC1255580,,,"The effects of feeding different levels of milk to diarrheic calves (n = 19) supplemented with oral electrolytes were investigated. In the early stages of the disease the calves were fed either enough milk to maintain normal growth in a healthy calf, one half that volume or no milk. The three groups were further subdivided according to whether or not the electrolyte solution contained bicarbonate. A full milk ration allowed uninterrupted weight gains of 1% body weight/day (p = 0.003), but caused greater inappetence (p = 0.003 to 0.037) at the beginning of the trial than lower levels of milk intake. Electrolyte solutions with bicarbonate reduced growth rates in milk fed calves (p = 0.014). The density of fat stores increased with the level of milk feeding (p = 0.04 to 0.053). The mitotic index of the duodenal mucosa increased with milk feeding (p = 0.08), indicating a superior mucosal regeneration potential. Thymic atrophy was pronounced in those calves fed no milk (p = 0.001). It was concluded that the continued feeding of milk to diarrheic calves was beneficial. Electrolyte solutions containing bicarbonate should be avoided when milk is fed to diarrheic calves.",,"['Heath, S E', 'Naylor, J M', 'Guedo, B L', 'Petrie, L', 'Rousseaux, C G', 'Radostits, O M']",,,,
,PMC,Coronavirus-associated diarrhea (winter dysentery) in adult cattle,,PMC1681282,,,,,"['Durham, Peter J.K.', 'Hassard, Lori E.', 'Armstrong, Ken R.', 'Naylor, Jonathan M.']",,,,
,PMC,Biochemical and clinical response of fulminant viral hepatitis to administration of prostaglandin E. A preliminary report.,,PMC329761,,,"The effect of PG on patients with fulminant and subfulminant viral hepatitis (FHF) was studied. 17 patients presented with FHF secondary to hepatitis A (n = 3), hepatitis B (n = 6), and non-A, non-B (NANB) hepatitis (n = 8). 14 of the 17 patients had stage III or IV hepatic encephalopathy (HE). At presentation the mean aspartate transaminase (AST) was 1,844 +/- 1,246 U/liter, bilirubin 232 +/- 135 mumol/liter, prothrombin time (PT) 34 +/- 18, partial thromboplastin time (PTT) 73 +/- 26 s, and coagulation Factors V and VII 8 +/- 4 and 9 +/- 5%, respectively. Intravenous PGE1 was initiated 24-48 h later after a rise in AST (2,195 +/- 1,810), bilirubin (341 +/- 148), PT (36 +/- 15), and PTT (75 +/- 18). 12 of 17 responded rapidly with a decrease in AST from 1,540 +/- 833 to 188 +/- 324 U/liter. Improvement in hepatic synthetic function was indicated by a decrease in PT from 27 +/- 7 to 12 +/- 1 s and PTT from 61 +/- 10 to 31 +/- 2 s, and an increase in Factor V from 9 +/- 4 to 69 +/- 18% and Factor VII from 11 +/- 5 to 71 +/- 20%. Five responders with NANB hepatitis relapsed upon discontinuation of therapy, with recurrence of HE and increases in AST and PT, and improvement was observed upon retreatment. After 4 wk of intravenous therapy oral PGE2 was substituted. Two patients with NANB hepatitis recovered completely and remained in remission 6 and 12 mo after cessation of therapy. Two additional patients continued in remission after 2 and 6 mo of PGE2. No relapses were seen in the patients with hepatitis A virus and hepatitis B virus infection. Liver biopsies in all 12 surviving patients returned to normal. In the five nonresponders an improvement in hepatic function was indicated by a fall in AST (3,767 +/- 2,611 to 2,142 +/- 2,040 U/liter), PT (52 +/- 25 to 33 +/- 18 s), and PTT (103 +/- 29 to 77 +/- 44 s), but all deteriorated and died of cerebral edema (n = 3) or underwent liver transplantation (n = 2). These results suggest efficacy of PGE for FHF, and further investigation is warranted.",,"['Sinclair, S B', 'Greig, P D', 'Blendis, L M', 'Abecassis, M', 'Roberts, E A', 'Phillips, M J', 'Cameron, R', 'Levy, G A']",,,,
,PMC,Glycine tRNA mutants with normal anticodon loop size cause -1 frameshifting.,,PMC298196,,,"Mutations in the acceptor stem, the 5-methyluridine-pseudouridine-cytidine (TFC) arm, and the anticodon of Salmonella tRNA2Gly can cause -1 frameshifting. The potential for standard base pairing between acceptor stem positions 1 and 72 is disrupted in the mutant sufS627. This disruption may interfere with the interaction of the tRNA with elongation factor-Tu.GTP or an as-yet-unspecified domain of the ribosome. The potential for standard base pairing in part of the TFC stem is disrupted in mutant sufS625. The nearly universal C-61 base of the TFC stem is altered in mutant sufS617, and the TFC loop is extended in mutant sufS605. These changes are expected to interfere with the stability of the TFC loop and its interaction with the D arm. The mutation in mutant sufS605, and possibly other mutants, alters nucleoside modification in the D arm. Three mutants, sufS601, sufS607, and sufS609, have a cytidine substituted for the modified uridine at position 34, the first anticodon position. None of the alterations grossly disrupts in-frame triplet decoding by the mutant tRNAs. The results show that -1 frameshifting in vivo can be caused by tRNAs with normal anticodon loop size and suggest that alternative conformational states of the mutant tRNAs may allow them to read a codon in frame or to shift reading frame.",,"[""O'Mahony, D J"", 'Mims, B H', 'Thompson, S', 'Murgola, E J', 'Atkins, J F']",,,,
,PMC,New nucleotide sequence data on the EMBL File Server,,PMC318461,,,,,,,,,
,PMC,"Broad-spectrum in vivo antiviral activity of 7-thia-8-oxoguanosine, a novel immunopotentiating agent.",,PMC172688,,,"A novel immunopotentiating agent, 5-amino-3-beta-D-ribofuranosylthiazolo [4,5-d]pyrimidine-2,7(3H,6H)-dione (7-thia-8-oxoguanosine), lacks virus-inhibitory properties in vitro but induces interferon and potentiates immune functions, such as natural killer cell activity. It was evaluated in rodent models to determine the spectrum of antiviral activity and effective treatment regimens. At 50 to 200 mg/kg given as single or divided intraperitoneal (i.p.) doses 1 day before virus inoculation, significant protection was afforded to mice infected i.p. with Semliki Forest, San Angelo, banzi, and encephalomyocarditis viruses. Similarly, suckling rats were protected from an intranasal challenge with rat coronavirus. Against San Angelo virus, treatments could be delayed to 1 day post-virus inoculation and still show a beneficial effect. The compound was moderately effective in mice infected i.p. with herpes simplex virus type 2 or intranasally with vesicular stomatitis virus. No activity was seen against influenza B virus in mice when the analog was administered one time pre-virus inoculation or in multiple doses given before and after the virus inoculation. Nor was there a prophylactic effect against herpetic skin lesions on mice. This immune modulator may have promise for the treatment of a variety of virus infections.",,"['Smee, D F', 'Alaghamandan, H A', 'Cottam, H B', 'Sharma, B S', 'Jolley, W B', 'Robins, R K']",,,,
,PMC,Overlapping genes in a yeast double-stranded RNA virus.,,PMC250995,,,"The Saccharomyces cerevisiae viruses have a large viral double-stranded RNA which encodes the major viral capsid polypeptide. We have previously shown that this RNA (L1) also encodes a putative viral RNA-dependent RNA polymerase (D. F. Pietras, M. E. Diamond, and J. A. Bruenn, Nucleic Acids Res., 16:6226, 1988). The organization and expression of the viral genome is similar to that of the gag-pol region of the retroviruses. The complete sequence of L1 demonstrates two large open reading frames on the plus strand which overlap by 129 bases. The first is the gene for the capsid polypeptide, and the second is the gene for the putative RNA polymerase. One of the products of in vitro translation of the denatured viral double-stranded RNA is a polypeptide of the size expected of a capsid-polymerase fusion protein, resulting from a -1 frameshift within the overlapping region. A polypeptide of the size expected for a capsid-polymerase fusion product was found in virions, and it was recognized in Western blots (immunoblots) by antibodies to a synthetic peptide derived from the predicted polymerase sequence.",,"['Diamond, M E', 'Dowhanick, J J', 'Nemeroff, M E', 'Pietras, D F', 'Tu, C L', 'Bruenn, J A']",,,,
,PMC,Severe thrombocytopenia in young calves experimentally infected with noncytopathic bovine viral diarrhea virus.,,PMC250990,,,"Seven calves between 1 week and 2 months of age were infected with a noncytopathic field isolate of bovine viral diarrhea virus (BDV) in order to evaluate the effect of BDV infection on the concentration of circulating platelets in the blood. All calves were determined to be free of BDV and neutralizing antibodies to BDV before infection. Platelet counts were performed on a daily basis over a 30-day period beginning at the time of infection. By 2 weeks postinfection, all calves showed a significant drop in the number of circulating platelets and a marked hyperplasia of megakaryocytes in the bone marrow. In three of the seven calves, thrombocytopenia was severe (less than or equal to 5,000/microliters) for 1 to 6 days. In two of these three animals, extensive petechial and ecchymotic hemorrhages were observed on all mucosal surfaces and on various internal organs during the period of severe thrombocytopenia. BDV was consistently isolated from the platelets during the early phases of the infection, and viral antigen was occasionally detected on platelets by a fluorescent-antibody assay. The results demonstrate that BDV infection is associated with decreases in platelet numbers and suggest that platelets may serve as carriers of circulating virus.",,"['Corapi, W V', 'French, T W', 'Dubovi, E J']",,,,
,PMC,Identification of a new transcriptional initiation site and the corresponding functional gene 2b in the murine coronavirus RNA genome.,,PMC250964,,,"We have previously shown that some strains of the murine coronavirus mouse hepatitis virus (MHV) synthesize an additional mRNA species (mRNA 2b, previously called mRNA 2a) with a size intermediate between that of mRNAs 2 and 3, suggesting the presence of an optional transcriptional initiation site. This transcriptional start is dependent on the leader sequence of the virus strains. To study the mechanism of coronavirus transcriptional regulation, we have cloned and sequenced the region of the viral genome corresponding to the 5' unique coding region of mRNA 2 of the JHM strain of MHV. In addition to the open reading frame (ORF) predicted to encode the viral nonstructural protein p30, a second complete ORF, with the potential to encode a 439-amino-acid polypeptide, was discovered. The transcriptional initiation sites of both mRNA 2a (formerly called mRNA 2) and mRNA 2b were determined by primer extension studies and RNA sequencing. The data indicated that transcription of mRNA 2a initiated at a site, UCUAUAC, that resembled the consensus intergenic sequence. In contrast, the start signal of the optional mRNA 2b, UAAUAAAC, deviated from the consensus sequence. mRNA 2b is a functional mRNA, as shown by in vitro translation studies of mRNA and ORF 2b and by the detection of an additional viral structural protein, gp65, in the JHM strain that synthesized this mRNA. Although the A59 strain of MHV was found to retain ORF 2b, it lacked the correct transcriptional and translational start signals for this gene. This study has therefore identified an optional gene product for murine coronaviruses and provided insights into the mechanism of regulation of MHV RNA transcription.",,"['Shieh, C K', 'Lee, H J', 'Yokomori, K', 'La Monica, N', 'Makino, S', 'Lai, M M']",,,,
,PMC,Identification of a domain required for autoproteolytic cleavage of murine coronavirus gene A polyprotein.,,PMC250960,,,"The 5'-most gene of the murine coronavirus genome, gene A, is presumed to encode viral RNA-dependent RNA polymerase. It has previously been shown that the N-terminal portion of this gene product is cleaved into a protein of 28 kilodaltons (p28). To further understand the mechanism of synthesis of the p28 protein, cDNA clones representing the 5'-most 5.3 kilobases of murine coronavirus mouse hepatitis virus strain JHM were sequenced and subcloned into pT7 vectors from which RNAs were transcribed and translated in vitro. The sequence was found to encode a single long open reading frame continuing from near the 5' terminus of the genome. Although p28 is encoded from the first 1 kilobase at the 5' end of the genome, translation of in vitro-transcribed RNAs indicated that this protein was not detected unless the product of the entire 5.3-kilobase region was synthesized. Translation of RNAs of 3.9 kilobases or smaller yielded proteins which contained the p28 sequence, but p28 was not cleaved. This suggests that the sequence in the region between 3.9 and 5.3 kilobases from the 5' end of the genomic RNA is essential for proteolytic cleavage and contains autoproteolytic activity. The p28 protein could not be cleaved from the smaller primary translation products of gene A, even in the presence of the larger autocleaving protein. Cleavage of the p28 protein was inhibited by addition of the protease inhibitor ZnCl2. This study thus identified a protein domain essential for autoproteolytic cleavage of the gene A polyprotein.",,"['Baker, S C', 'Shieh, C K', 'Soe, L H', 'Chang, M F', 'Vannier, D M', 'Lai, M M']",,,,
,PMC,"Insertion of proteins into bacterial membranes: mechanism, characteristics, and comparisons with the eucaryotic process.",,PMC372740,,,,,"['Saier, M H', 'Werner, P K', 'Müller, M']",,,,
,PMC,Errors and alternatives in reading the universal genetic code.,,PMC372737,,,,,"Parker, J",,,,
,PMC,"Nucleotide sequence of the gene coding for the peplomer protein (= spike protein) of infectious bronchitis virus, strain D274.",,PMC318367,,,,,"['Jordi, B J', 'Kremers, D A', 'Kusters, H G', 'van der Zeijst, B A']",,,,
,PMC,Nucleotide sequence of the human coronavirus HCV 229E mRNA 4 and mRNA 5 unique regions.,,PMC318288,,,,,"['Raabe, T', 'Siddell, S']",,,,
,PMC,Serodiagnosis of scrub typhus with antigens immobilized on nitrocellulose sheet.,,PMC267681,,,"This study was designed to develop a simple method for serodiagnosis of scrub typhus. The basis of the method is detection of anti-Rickettsia tsutsugamushi antibody in patient serum by reaction with antigens dot blotted on a nitrocellulose sheet (NCS). The final evaluation of the reaction is performed by observing the color intensity which develops as a result of sequential treatments of the NCS with peroxidase-conjugated anti-human immunoglobulin G or immunoglobulin M antibody and with the substrate of the enzyme. After various trials, we found that the best results were obtained by using a purified antigen which adhered to an NCS at 0.2 to 2 micrograms of protein per dot and a test serum diluted 1,000- to 4,000-fold. Under these conditions, almost all antibody-positive sera showed a distinct color at the dot on the NCS, so that a positive reaction could be distinguished by the naked eye from a negative reaction with antibody-negative sera, which developed only a faint color. A comparison of the results of screening of antibody-positive and -negative sera by this method and the immunofluorescence test showed that both methods produced similar results. From these results, it is concluded that this dot immunoassay can be useful for the serodiagnosis of scrub typhus.",,"['Urakami, H', 'Yamamoto, S', 'Tsuruhara, T', 'Ohashi, N', 'Tamura, A']",,,,
,PMC,Isolation of peplomer glycoprotein E2 of transmissible gastroenteritis virus and application in enzyme-linked immunosorbent assay.,,PMC267667,,,"An enzyme-linked immunosorbent assay (ELISA) based on peplomer glycoprotein E2 was developed for the detection of antibodies to transmissible gastroenteritis virus (TGEV). Purified preparations of E2 were isolated by solubilization of the viral membrane with nonion detergent Nonidet P-40, followed by sucrose density gradient sedimentation. ELISA optical density values with E2 antigen significantly exceeded the indices when other TGEV protein or intact virion antigen was used. It was shown that a virus protein concentration in the E2 preparation of 500 ng per well is sufficient to sensitize the solid phase of microplates. A comparison of the ELISA and the virus neutralization test for the detection of TGEV antibodies was conducted. A significant correlation between the ELISA and the virus neutralization test was shown (r = 0.97). This serological test may be successfully used for various immunologic investigations.",,"['Rukhadze, G G', 'Aliper, T I', 'Sergeev, V A']",,,,
,PMC,Interplay between carbohydrate in the stalk and the length of the connecting peptide determines the cleavability of influenza virus hemagglutinin.,,PMC250901,,,"The ability of many viruses to replicate in host cells depends on cleavage of certain viral glycoproteins, including hemagglutinin (HA). By generating site-specific mutant HAs of two highly virulent influenza viruses, we established that the relationship between carbohydrate in the stalk and the length of the connecting peptide is a critical determinant of cleavability. HAs that lacked an oligosaccharide side chain in the stalk were cleaved regardless of the number of basic amino acids at the cleavage site, whereas those with the oligosaccharide side chain resisted cleavage unless additional basic amino acids were inserted. This finding suggests that the oligosaccharide side chain interferes with HA cleavage if the number of basic amino acids at the cleavage site is not adequate to nullify this effect. Similar interplay could influence cleavage of other viral glycoproteins, such as those of human and simian immunodeficiency viruses and paramyxoviruses.",,"['Kawaoka, Y', 'Webster, R G']",,,,
,PMC,Production of tumor necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neurotropic virus.,,PMC297836,,,"Rat astrocytes, immunologically competent glial cells of the central nervous system (CNS), released a variety of cytokines after activation. Lipopolysaccharide-stimulated astrocytes produced tumor necrosis factor (TNF) as demonstrated by Northern blot analysis using a mouse TNF probe and by functional assay. Biological activity of rat astrocyte-derived TNF was neutralized by rabbit antiserum against recombinant murine TNF. Stimulation of astrocytes by lipopolysaccharide also activated the interleukin 1 and interleukin 6 genes. We have also investigated whether a neurotropic paramyxovirus, Newcastle disease virus, triggers cytokine production by astrocytes. This virus induced astrocytes to produce TNF, lymphotoxin, interleukin 6, and alpha- and beta-interferons. Thus, stimulation by endotoxin and virus activated distinct, yet overlapping, sets of cytokine genes. We propose that astrocytes and the cytokines they produce may play a significant role in the pathogenesis of immunologically and/or virally mediated CNS disease, in CNS intercellular communication, and in the interactions between the nervous and immune systems.",,"['Lieberman, A P', 'Pitha, P M', 'Shin, H S', 'Shin, M L']",,,,
,PMC,The sequence of cDNA of bovine coronavirus 32K nonstructural gene.,,PMC318210,,,,,"['Cox, G J', 'Parker, M D', 'Babiuk, L A']",,,,
,PMC,Diagnosis of copper deficiency and effects of supplementation in beef cows.,,PMC1255723,,,"The effects of feeding supplementary dietary copper to a herd of 400 beef cows, were studied over a two year period. In the first year of the trial, the calves showed clinical signs of copper deficiency. There was improved growth following subcutaneous injection of copper ethylenediamine tetraacetate, and the treated calves had a 2.8% increase in adjusted weaning weights. In the second year of the trial pregnant cows were fed a basal ration of bromegrass silage, barley and minerals over the winter feeding period. The feed was supplemented with copper so that half received 5.5 mg/kg of copper on a dry matter basis and half 40 mg/kg. Calving occurred in the spring and half the calves were treated with injectable copper at birth and again at 12 weeks of age. There was no evidence of copper deficiency in the calves and there was no effect of high level copper supplementation on calf birth weight, or neutrophil candidacidal activity. Susceptibility to diarrhea varied in a complex fashion; morbidity was lowest in calves born to dams fed supplementary copper and highest in calves born to supplemented dams and injected with copper at birth. The cows and calves grazed the same copper deficient pasture over the summer. The average daily gain for calves born to supplemented cows was 0.999 +/- 0.010 kg/day (x +/- SEM) which was significantly greater than the 0.972 +/- 0.009 kg/day for calves from nonsupplemented dams (p = 0.044). The benefit of copper supplementation on 200 day weaning weight was estimated at 4.8 kg. Evidence of copper deficiency was seen when a herd test showed mean serum levels below 9 mumol/L and liver values below 0.09 mmol/kg wet matter.",,"['Naylor, J M', 'Kasari, T R', 'Blakley, B R', 'Townsend, H G']",,,,
,PMC,Health and metabolic responses of young calves housed at -30 degrees C to -8 degrees C.,,PMC1255709,,,"Newborn, male, Holstein calves, were continuously housed for three weeks in calf hutches at 17 degrees C or in a thermal environment which varied rhythmically on a daily basis either between -20 degrees C and -8 degrees C (experiment A) or between -30 degrees C and -18 degrees C (experiment B). Compared to warm-housed calves, cold-housed calves in experiment A had metabolic rates which were significantly higher (p less than 0.001) in a standing position but which were not significantly different (p less than 0.05) in a recumbent position. Recumbent and standing cold-housed calves in experiment B had an increased (p less than 0.05) metabolic rate compared to warm-housed controls. Heat loss was less (p less than 0.05) for recumbent cold-housed calves in experiment B than for standing calves in a thermoneutral environment. Localized subcutaneous hemorrhages of hindlimbs were a consistent necropsy finding among all cold-housed calves. Average daily gains of cold-housed calves were not significantly different from warm-housed controls. Clinical, physiological and pathological findings indicated that cold treatments used in the present study did not cause serious harm to calves. It was concluded that calves housed in properly managed hutches are remarkably cold tolerant.",,"['Rawson, R E', 'Dziuk, H E', 'Good, A L', 'Anderson, J F', 'Bates, D W', 'Ruth, G R', 'Serfass, R C']",,,,
,PMC,A retrospective study of the relationship between clinical signs and severity of acidosis in diarrheic calves,,PMC1681086,,,"A retrospective study of 123 calves under two months of age with signs of diarrhea was performed to investigate the relationships among the calf's demeanor, dehydration, rectal temperature, and base deficit. The severity of dehydration, hypothermia, and metabolic acidosis were associated with level of depression. Clinical signs and age of calf could be used to predict the severity of acidosis. Acidosis was more severe in calves over eight days of age and also increased in severity with the degree of depression. The most severe metabolic acidosis was seen in calves over eight days of age presented in sternal or lateral recumbency; the base deficit in these groups was 16.3 ± 8.3 (means ± 1SD) and 20.3 ± 10.1 mmol/L respectively, and on average these calves require 2.4 and 3.0 L respectively of 1.3% sodium bicarbonate solution to correct the acidosis.",,"Naylor, Jonathan M.",,,,
,PMC,Suppression of a -1 frameshift mutation by a recessive tRNA suppressor which causes doublet decoding.,,PMC210131,,,"sufS was found to suppress the only known suppressible-1 frameshift mutation, trpE91, at a site identified as GGA and mapped within the single gene of the only tRNA that can decode GGA in Escherichia coli. It mapped to the same gene in Salmonella typhimurium. sufS alleles were recessive, and dominant alleles could not be isolated. This is in contrast to all other tRNA structural gene mutations identified thus far that cause frameshift suppression. The recessiveness implies that all sufS alleles are poor competitors against their wild-type tRNA(Gly2) counterparts. The base G immediately 5' of the GGA suppression site influenced the level but was not critical for suppression by sufS601. From this result, it is inferred that sufS601 causes frameshifting by doublet decoding.",,"[""O'Mahony, D J"", 'Hughes, D', 'Thompson, S', 'Atkins, J F']",,,,
,PMC,Haemophilus infection in a colony of laboratory rats.,,PMC267629,,,"During routine quality control of laboratory rodents, short gram-negative rods with satellite growth adjacent to a Staphylococcus strain were isolated from rats. They proved to be members of the family Pasteurellaceae. On the basis of their dependence on V factor they were classified as Haemophilus sp. Systematic investigations in our laboratory rat colony revealed a high prevalence of these bacteria. They were isolated from 75 of 446 rats (16.8%) which were monitored by culture during a 2-year investigation. Most strains were isolated from the lungs and the trachea; some were cultured from the nasal cavity and the female genital tract. Antibodies to these bacteria were detected in sera from 385 of 829 rats (46.5%) by using an indirect immunofluorescence test. The majority of culturally and serologically positive animals came from three separate holding areas; they all came from the same breeder. Investigation of rats immediately on receipt from the breeder showed that they were culturally and serologically positive for Haemophilus sp. Histological examination of rats which were monoinfected with Haemophilus sp. showed a mild inflammatory cell infiltration in the lungs and a light diffuse hyperemia. In the physiological and biochemical investigations of 53 isolates, all strains had an identical biochemical profile. On the basis of the 35 criteria examined, a definite classification is not possible. These Haemophilus bacteria are probably members of a hitherto unknown species.",,"Nicklas, W",,,,
,PMC,T-cell-mediated clearance of mouse hepatitis virus strain JHM from the central nervous system.,,PMC250860,,,Clearance of the neurotropic JHM strain of mouse hepatitis virus from the central nervous system was examined by the transfer of spleen cells from immunized donors. A T cell with the surface phenotype of Thy1.2+ CD4+ CD8- asialo-GM1+ Mac-1- was found to be necessary for viral clearance. The surface phenotype and adherence to nylon wool suggest that these cells are activated helper-inducer T cells. Adoptive transfer to congenic histocompatibility strains demonstrated the necessity for compatibility at the D locus of the major histocompatibility complex. The expression of the CD4 surface marker and the requirement for major histocompatibility complex class I were further studied by the transfer of cells to recipients treated with anti-CD4 or anti-CD8 monoclonal antibodies. Treatment of recipients with either the anti-CD8 or the anti-CD4 antibodies inhibited virus clearance from the central nervous system. This suggests that the CD4+ cell acts as a helper and that virus is cleared from the central nervous system. This suggests that the CD4+ cell acts as a helper and that virus is cleared from the central nervous system by CD8+ cells that recognize viral antigen in the context of the H-2Db gene product.,,"['Sussman, M A', 'Shubin, R A', 'Kyuwa, S', 'Stohlman, S A']",,,,
,PMC,Coronavirus subgenomic minus-strand RNAs and the potential for mRNA replicons.,,PMC297677,,,"The genome of the porcine transmissible gastroenteritis coronavirus is a plus-strand, polyadenylylated, infectious RNA molecule of approximately 20 kilobases. During virus replication, seven subgenomic mRNAs are generated by what is thought to be a leader-priming mechanism to form a 3'-coterminal nested set. By using radiolabeled, strand-specific, synthetic oligodeoxynucleotide probes in RNA blot hybridization analyses, we have found a minus-strand counterpart for the genome and for each subgenomic mRNA species in the cytoplasm of infected cells. Subgenomic minus strands were found to be components of double-stranded replicative forms and in numbers that surpass full-length antigenome. We propose that subgenomic mRNA replication, in addition to leader-primed transcription, is a significant mechanism of mRNA synthesis and that it functions to amplify mRNAs. It is a mechanism of amplification that has not been described for any other group of RNA viruses. Subgenomic replicons may also function in a manner similar to genomes of defective interfering viruses to lead to the establishment of persistent infections, a universal property of coronaviruses.",,"['Sethna, P B', 'Hung, S L', 'Brian, D A']",,,,
,PMC,Coronavirus genome: prediction of putative functional domains in the non-structural polyprotein by comparative amino acid sequence analysis.,,PMC318036,,,"Amino acid sequences of 2 giant non-structural polyproteins (F1 and F2) of infectious bronchitis virus (IBV), a member of Coronaviridae, were compared, by computer-assisted methods, to sequences of a number of other positive strand RNA viral and cellular proteins. By this approach, juxtaposed putative RNA-dependent RNA polymerase, nucleic acid binding (""finger""-like) and RNA helicase domains were identified in F2. Together, these domains might constitute the core of the protein complex involved in the primer-dependent transcription, replication and recombination of coronaviruses. In F1, two cysteine protease-like domains and a growth factor-like one were revealed. One of the putative proteases of IBV is similar to 3C proteases of picornaviruses and related enzymes of como- nepo- and potyviruses. Search of IBV F1 and F2 sequences for sites similar to those cleaved by the latter proteases and intercomparison of the surrounding sequence stretches revealed 13 dipeptides Q/S(G) which are probably cleaved by the coronavirus 3C-like protease. Based on these observations, a partial tentative scheme for the functional organization and expression strategy of the non-structural polyproteins of IBV was proposed. It implies that, despite the general similarity to other positive strand RNA viruses, and particularly to potyviruses, coronaviruses possess a number of unique structural and functional features.",,"['Gorbalenya, A E', 'Koonin, E V', 'Donchenko, A P', 'Blinov, V M']",,,,
,PMC,"Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes.",,PMC318027,,,"In the course of systematic analysis of protein sequences containing the purine NTP-binding motif, a new superfamily was delineated which included 25 established or putative helicases of Escherichia coli, yeast, insects, mammals, pox- and herpesviruses, a yeast mitochondrial plasmid and three groups of positive strand RNA viruses. These proteins contained 7 distinct highly conserved segments two of which corresponded to the ""A"" and ""B"" sites of the NTP-binding motif. Typical of the new superfamily was an abridged consensus for the ""A"" site, GxGKS/T, instead of the classical G/AxxxxGKS/T. Secondary structure predictions indicated that each of the conserved segments might constitute a separate structural unit centering at a beta-turn. All previously characterized mutations impairing the function of the yeast helicase RAD3 in DNA repair mapped to one of the conserved segments. A degree of similarity was revealed between the consensus pattern of conserved amino acid residues derived for the new superfamily and that of another recently described protein superfamily including a different set of prokaryotic, eukaryotic and viral (putative) helicases.",,"['Gorbalenya, A E', 'Koonin, E V', 'Donchenko, A P', 'Blinov, V M']",,,,
,PMC,Topology of the non-structural rotavirus receptor glycoprotein NS28 in the rough endoplasmic reticulum.,,PMC401011,,,"The rotavirus non-structural glycoprotein (NS28), the receptor for the virus core during budding into the lumen of the rough endoplasmic reticulum (RER), is 175 amino acids long and possesses an uncleaved signal sequence and two amino-terminal glycosylation sites. Utilizing one of three potential hydrophobic domains, the protein spans the membrane only once, with the glycosylated amino-terminal region oriented to the luminal side of the ER and the carboxy-terminal region to the cytoplasmic side. To localize sequences involved in translocation of NS28, we constructed a series of mutations in the coding regions for the hydrophobic domains of the protein. Mutant protein products were studied by in vitro translation and by transfection in vivo. In transfected cells, all mutant forms localize to the ER, and none are secreted. In vitro, each of the three hydrophobic domains is able to associate with microsomes. However, glycosylation and proteolysis of wild-type and mutant forms of NS28 indicates that the wild-type protein is anchored in the membrane only by the second hydrophobic domain, leaving approximately 131 residues exposed on the cytoplasmic side for receptor - ligand interaction.",,"['Bergmann, C C', 'Maass, D', 'Poruchynsky, M S', 'Atkinson, P H', 'Bellamy, A R']",,,,
,PMC,Chemical disinfection of non-porous inanimate surfaces experimentally contaminated with four human pathogenic viruses.,,PMC2249473,,,"The chemical disinfection of virus-contaminated non-porous inanimate surfaces was investigated using coxsackievirus B3, adenovirus type 5, parainfluenza virus type 3 and coronavirus 229E as representatives of important nosocomial viral pathogens. A 10 microliter amount of the test virus, suspended in either faeces or mucin, was placed onto each stainless steel disk (about 1 cm in diameter) and the inoculum allowed to dry for 1 h under ambient conditions. Sixteen disinfectant formulations were selected for this study based on the findings of an earlier investigation with a human rotavirus. After 1 min exposure to 20 microliters of the disinfectant, the virus from the disks was immediately eluted into tryptose phosphate broth and plaque assayed. Using an efficacy criterion of a 3 log10 or greater reduction in virus infectivity titre and irrespective of the virus suspending medium, only the following five disinfectants proved to be effective against all the four viruses tested: (1) 2% glutaraldehyde normally used as an instrument soak, (2) a strongly alkaline mixture of 0.5% sodium o-benzyl-p-chlorophenate and 0.6% sodium lauryl sulphate, generally used as a domestic disinfectant cleaner for hard surfaces, (3) a 0.04% solution of a quaternary ammonium compound containing 7% hydrochloric acid, which is the basis of many toilet bowl cleaners, (4) chloramine T at a minimum free chlorine level of 3000 p.p.m. and (5) sodium hypochlorite at a minimum free chlorine concentration of 5000 p.p.m. Of those chemicals suitable for use as topical antiseptics, 70% ethanol alone or products containing at least 70% ethanol were ineffective only against coxsackievirus B3. These results emphasize the care needed in selecting chemical disinfectants for routine use in infection control.",,"['Sattar, S. A.', 'Springthorpe, V. S.', 'Karim, Y.', 'Loro, P.']",,,,
,PMC,Antiviral antibodies stimulate production of reactive oxygen species in cultured canine brain cells infected with canine distemper virus.,,PMC250781,,,"Canine distemper is characterized mainly by respiratory, enteric, and nervous symptoms. Infection of the central nervous system results in demyelination, to which inflammation has been shown to contribute significantly. It has been proposed that macrophages play a major role as effector cells in this process. We report that cultured dog brain cells contain a population of macrophages capable of producing reactive oxygen species as measured by luminol-dependent chemiluminescence. In cultures infected with canine distemper virus, a burst of reactive oxygen is triggered by antiviral antibody. This response depends on the presence of viral antigens on the surfaces of infected cells and is mediated by the interaction of antigen-bound antibody with Fc receptors on the macrophages. Since there is no evidence in vitro or in vivo that oligodendrocytes, the cells forming myelin, are infected, our observation supports the hypothesis that ""innocent bystander killing"" is important in demyelination caused by canine distemper virus. Reactive oxygen species released from macrophages may contribute to destruction of myelin.",,"['Bürge, T', 'Griot, C', 'Vandevelde, M', 'Peterhans, E']",,,,
,PMC,"Oligomeric structure of gp41, the transmembrane protein of human immunodeficiency virus type 1.",,PMC250755,,,"We characterized the structural forms of the human immunodeficiency virus env-encoded proteins with a panel of monoclonal and polyclonal antibodies. Western blot (immunoblot) assays with antibodies specific for gp41 invariably recognized a major component of 160 kilodaltons and a less intense component of 120 kilodaltons in viral lysates. We demonstrated that these species are noncovalently associated tetramers and trimers of gp41 which represent the native form of this protein in virions. These complexes were stable when boiled in the presence of low concentrations of sodium dodecyl sulfate but were dissociated to gp41 monomers at high sodium dodecyl sulfate concentrations. Moreover, two human monoclonal antibodies preferentially recognized the oligomeric complexes over monomeric gp41 in Western blots, indicating the presence of epitopes recognized by the human immune system on the gp41 multimers which are not efficiently expressed by the dissociated monomers. The demonstration of the existence of multimeric env complexes and the enhanced and altered antigenicity of such multimers may be relevant to the design of subunit and recombinant human immunodeficiency virus env vaccines.",,"['Pinter, A', 'Honnen, W J', 'Tilley, S A', 'Bona, C', 'Zaghouani, H', 'Gorny, M K', 'Zolla-Pazner, S']",,,,
,PMC,Reactivity of T cells in mycosis fungoides exhibiting marked epidermotropism with the monoclonal antibody HML-1 that defines a membrane molecule on human mucosal lymphocytes.,,PMC1879905,,,"Twenty-eight cases of cutaneous T cell lymphomas of mycosis fungoides type, 8 of which showed a marked epidermotropism, were investigated for their reactivity with the monoclonal antibody HML-1. This reagent selectively recognizes human benign and malignant intestinal T lymphocytes, but not benign or malignant lymph node T cells. In all cases, the majority of nonepithelium-associated T cells present in the corium were HML-1 negative. In the eight cases with marked epidermotropism, the intraepidermal (IED) T cells were HML-1 positive in three cases, and HML-1 negative in the remaining five cases. The HML-1 positive IED T cells tended to be localized preferentially in the basal layers, whereas the HML-1 negative IED T cells were more diffusely distributed throughout all epidermal cell layers or formed intra-epidermal aggregates. These findings provide further evidence that mycosis fungoides is not a single entity, but represents a group of neoplasms originating from different T cell subsets that have in common their tropism to epidermis and/or dermis, and thus have a similar clinical presentation.",,"['Sperling, M.', 'Kaudewitz, P.', 'Braun-Falco, O.', 'Stein, H.']",,,,
,PMC,Replication of parainfluenza (Sendai) virus in isolated rat pulmonary type II alveolar epithelial cells.,,PMC1879904,,,"The major objectives of this study were to determine whether alveolar type II epithelial cells isolated from rat lung and maintained in tissue culture would support productive replication of parainfluenza type 1 (Sendai) virus and to determine whether isolated type II cells from neonatal (5-day-old) rats that are more susceptible to viral-induced alveolar dysplasia supported viral replication to a greater extent than those from weanling (25-day-old) rats. Isolated and cultured type II cells from neonatal and weanling rats that were inoculated with Sendai virus supported productive replication as indicated by ultrastructural identification of budding virions and viral nucleocapsids in type II cells and by demonstration of rising titers of infectious virus from inoculated type II cell cultures. Alveolar macrophages from neonatal and weanling rats also supported viral replication, although infectious viral titers in macrophage cultures were lower than those from type II cell cultures. Only minor differences were detected between viral titers from neonatal and weanling type II epithelial cell cultures. Higher densities of viral nucleocapsids were observed in neonatal type II cells than in those from weanling rats. The results indicate that isolated type II alveolar epithelial cells support productive replication of parainfluenza virus and that type II cells are probably more efficient in supporting productive viral replication than are alveolar macrophages.",,"['Castleman, W. L.', 'Northrop, P. J.', 'McAllister, P. K.']",,,,
,PMC,"Influenza C virus esterase: analysis of catalytic site, inhibition, and possible function.",,PMC250621,,,"The active site serine of the acetylesterase of influenza C virus was localized to amino acid 71 of the hemagglutinin-esterase protein by affinity labeling with 3H-labeled diisopropylfluorophosphate. This serine and the adjacent amino acids (Phe-Gly-Asp-Ser) are part of a consensus sequence motif found in serine hydrolases. Since comparative analysis failed to reveal esterase sequence similarities with other serine hydrolases, we suggest that this viral enzyme is a serine hydrolase constituting a new family of serine esterases. Furthermore, we found that the influenza C virus esterase was inhibited by isocoumarin derivatives, with 3,4-dichloroisocoumarin being the most potent inhibitor. Addition of this compound prevented elution of influenza C virus from erythrocytes and inhibited virus infectivity, possibly through inhibition of virus entry into cells.",,"['Vlasak, R', 'Muster, T', 'Lauro, A M', 'Powers, J C', 'Palese, P']",,,,
,PMC,Why are meaningful field trials difficult to achieve for bovine respiratory disease vaccines?,,PMC1681206,,,,,"Wilson, Susan H.",,,,
,PMC,Herd effects in trials of animal biologics,,PMC1681205,,,,,"Waltner-Toews, David",,,,
,PMC,"Viruses in acute gastroenteritis in children in Pune, India.",,PMC2249429,,,"A 2-year study from January 1981 to December 1982 was undertaken to determine the role of viruses in the causation of diarrhoea in hospitalized children in Pune, Maharashtra State, India. The stool samples of 426 children (213 diarrhoeal and 213 non-diarrhoeal controls) were investigated by electron microscopy and ELISA for the presence of viruses. Six morphologically distinct viruses were visualized: rotavirus, coronavirus-like particles (CVLP), adenovirus, astrovirus, calicivirus and small round virus-like particles (SRV). Rotavirus was detected in 28.6% of the diarrhoeal patients and in 1.4% of the controls. The frequency of infection with rotavirus was highest in the children aged less than 5 years. The mean age of rotavirus-positive patients was 11 months. Although rotavirus was detected in almost every month, there has a seasonal trend for colder months when CVLP cases were fewest. However, the prevalence of CVLP was greater in the control group (23.0%) rather than in those with diarrhoea (8.9%). In the control group, CVLP were detected more frequently during the summer months. An inverse relationship between CVLP and rotavirus was observed in children. Adenovirus, astrovirus, calicivirus and SRV were detected in a small proportion of children with and without clinical symptoms of gastroenteritis.",,"['Singh, P. B.', 'Sreenivasan, M. A.', 'Pavri, K. M.']",,,,
,PMC,In situ Ia expression on brain cells in the rat: autoimmune encephalomyelitis-resistant strain (BN) and susceptible strain (Lewis) compared.,,PMC1385168,,,"In order to examine in situ Ia expression on brain cells of various strains of rat, experimental autoimmune encephalomyelitis (EAE) was induced in both EAE-susceptible (LEW) and EAE-resistant (BN) strains. For induction of EAE in the resistant strain, two methods were applied: one was injection of guinea-pig myelin basic protein (GPBP) in complete Freund's adjuvant into LBNF1----BN chimeras; the other was transfer of GPBP-reactive T-line cells from BN rats into syngeneic rats. LBNF----BN chimeras developed clinical EAE, whereas BN rats that received T-line cells did not. However, histological EAE was apparent in both groups. Immunohistochemical examination using two different monoclonal antibodies (OX3 and OX6) against rat Ia antigens revealed that microglia of LEW, BN and chimera rats expressed Ia antigens in the central nervous system (CNS) with EAE. On the other hand, astrocytes were negative for Ia antigens in all the strains. Furthermore, quantitative analysis was undertaken in order to compare the density of Ia-positive microglia in the BN CNS with that in the LEW CNS. It was revealed that the density of Ia-positive microglia in the vicinity of perivascular inflammatory cell aggregates was essentially the same in both strains regardless of the difference in methods of EAE induction or histological severity of the disease. Ia-positive microglia remote from inflammatory cell aggregates were somewhat fewer in rats with mild histological EAE. However, no strain difference was noted in this analysis. Therefore, we concluded that in situ Ia-inducibility on the brain cells of EAE-resistant rats is not different from that of EAE-susceptible rats. Although Ia-positive microglia in both strains may be involved in the immune responses in the CNS, it is unlikely that the difference in Ia-inducibility on brain cells would contribute to strain-specific susceptibility to EAE.",,"['Matsumoto, Y', 'Kawai, K', 'Fujiwara, M']",,,,
,PMC,Virus Infections and the Developing Nervous System,,PMC1032327,,,,,"Robinson, RO",,,,
,PMC,Recurrent and Chronic Psychoses (British Medical Bulletin Vol 43: No 3),,PMC1032326,,,,,"Treasure, Janet",,,,
,PMC,A neutralization-resistant Theiler's virus variant produces an altered disease pattern in the mouse central nervous system.,,PMC248382,,,"Theiler's murine encephalomyelitis virus infection of mice is an animal model for human demyelinating diseases. To further define the role of this virus in the disease process, we selected a virus variant resistant to neutralization by a monoclonal antibody to VP-1. This virus variant was then injected into SJL/J mice. Central nervous system tissue was compared between variant virus- and wild-type virus-infected mice. Within the brain, no large differences were observed between the two groups as to the distribution of inflammatory infiltrates around the injection site and the number of viral antigen-positive cells during the first weeks of the observation period. In contrast, in the spinal cord major differences were found between variant virus- and wild-type virus-infected mice regarding the number of inflammatory lesions, infected cells, and the size of the areas involved with time. By immunohistochemistry, equivalent numbers of infected cells could be found in the spinal cord 1 week postinfection (p.i.): however, after that time, the number of infected cells in the wild-type virus-infected mice continued to increase, whereas the virus-positive cells from the variant virus-infected mice gradually decreased. Thus, the number of viral antigen-containing cells peaked by 1 week p.i. in the variant virus-infected animals. Conversely, the number of infected cells in the spinal cords from mice inoculated with wild-type virus steadily increased until 8 weeks p.i. At this time (8 weeks p.i.), no more variant virus antigen-positive cells could be observed within the spinal cord. Plaque assay of central nervous system tissue confirmed these differences between the two groups observed by immunohistochemistry. No infectious variant virus could be isolated after 2 weeks p.i. from the brain and 4 weeks p.i. from the spinal cord, whereas infectious wild-type virus could be detected up to the end of the observation period (12 weeks p.i.). Virus which was isolated from variant virus-infected mice still retained the neutralization-resistant phenotype. These studies emphasize the important biological in vivo activity of Theiler's virus VP-1 in determining neurovirulence.",,"['Zurbriggen, A', 'Fujinami, R S']",,,,
,PMC,Acylation of viral and eukaryotic proteins.,,PMC1138413,,,,,"Grand, R J",,,,
,PMC,Safety and tolerance of ocular administration of recombinant alpha interferon.,,PMC171501,,,"The safety, tolerance, and levels of drug in the nasal cavity produced by an ocular formulation of interferon were determined at four dosages in a placebo-controlled, double-masked trial. Interferon given by the ocular route was generally well tolerated, although a dose-related occurrence of subjective symptoms was detected.",,"['Turner, R B', 'Durcan, F J', 'Albrecht, J K', 'Crandall, A S']",,,,
,PMC,Detection of rotavirus and coronavirus shedding in two beef cow herds in Idaho,,PMC1680991,,,"Fecal samples were taken at the time of pregnancy examinations and at parturition from two beef herds. They were also taken from sick calves at the onset of disease, and from 25% of the healthy calves at 15 days of age. All fecal samples were examined by electron microscopy for viruses. Four cows in herd A were detected excreting coronavirus, one at the time of the pregnancy examinations and three at parturition. The first cow was removed from the herd and the others calved at the end of the season. There were no sick calves. No cows in herd B were detected excreting virus at the time of pregnancy checks, but fourteen coronavirus and two rotavirus carrier cows were found at parturition. All but two calves sampled had large numbers of virus particles in their feces. Clinical illness was associated with dams shedding virus and with nightly low temperatures.",,"['Bulgin, Marie S.', 'Ward, Alton C.S.', 'Barrett, Dannie P.', 'Lane, V. Michael']",,,,
,PMC,What's new in the pathogenesis of multiple sclerosis? A review.,,PMC1292042,,,,,"Chataway, S J",,,,
,PMC,Amino acid sequence of a conserved neutralizing epitope of murine coronaviruses.,,PMC247841,,,"We identified the binding site of monoclonal antibody 19.2, which cross-neutralizes several mouse hepatitis virus (MHV) strains, inhibits fusion of MHV-infected cells, and protects against lethal infection (P. J. Talbot and M. J. Buchmeier, Virus Res. 2:317-328, 1985). We used fusion proteins, generated by expression of fragments of the MHV A59 E2 gene in pEX plasmids, and synthetic peptides in a PEPSCAN.",,"['Luytjes, W', 'Geerts, D', 'Posthumus, W', 'Meloen, R', 'Spaan, W']",,,,
,PMC,Herpes simplex virus glycoprotein D mediates interference with herpes simplex virus infection.,,PMC247755,,,"We showed that the expression of a single protein, glycoprotein D (gD-1), specified by herpes simplex virus type 1 (HSV-1) renders cells resistant to infection by HSV but not to infection by other viruses. Mouse (LMtk-) and human (HEp-2) cell lines containing the gene for gD-1 under control of the human metallothionein promoter II expressed various levels of gD-1 constitutively and could be induced to express higher levels with heavy metal ions. Radiolabeled viruses bound equally well to gD-1-expressing and control cell lines. Adsorbed viruses were unable to penetrate cells expressing sufficient levels of gD-1, based on lack of any cytopathic effects of the challenge virus and on failure to detect either the induction of viral protein synthesis or the shutoff of host protein synthesis normally mediated by a virion-associated factor. The resistance to HSV infection conferred by gD-1 expression was not absolute and depended on several variables, including the amount of gD-1 expressed, the dosage of the challenge virus, the serotype of the challenge virus, and the properties of the cells themselves. The interference activity of gD-1 is discussed in relation to the role of gD-1 in virion infectivity and its possible role in permitting escape of progeny HSV from infected cells.",,"['Johnson, R M', 'Spear, P G']",,,,
,PMC,"Genetic characterization of FLA, the cat major histocompatibility complex.",,PMC286595,,,"The major histocompatibility complex (MHC) of the domestic cat (termed FLA) has been refractile to genetic and serological definition largely because of repeated failure to detect cytotoxic antibodies in multiparous cats or to elicit antibody following allogeneic lymphocyte immunization. We have developed a protocol for producing cytotoxic alloantisera in the cat following rejection of multiple surgical skin grafts. Of 59 cats subjected to grafting, 13 produced lymphocytotoxic antisera which had varying specificities among a panel of outbred cat cells. A population cluster analysis of the 13 alloantisera permitted the identification of six clusters of overlapping FLA specificities. Serological analysis of cells from 12 cat kindreds led to the definition of 24 allogeneic haplotypes, which segregate as a single Mendelian complex. Feline FLA antisera were characterized as class I or class II specific by immunoprecipitation of FLA gene products on lymphocyte cell surfaces. Abundant antigenic polymorphisms for both class I and class II MHC determinants were discovered, a result consistent with precedence in other species and the common expectation of the adaptive value of MHC variation. Development of feline MHC typing reagents and the definition of haplotypes for the cat hold promise for experimental analysis of valuable feline models for virus-induced immune deficiencies.",,"['Winkler, C', 'Schultz, A', 'Cevario, S', ""O'Brien, S""]",,,,
,PMC,Vaccins viraux: principes et perspectives,,PMC2491255,,,,,"Melnick, J.L.",,,,
,PMC,The interferon sensitivity of selected porcine viruses.,,PMC1255513,,,"The objective of this study was to compare the sensitivity of 11 porcine viruses to the antiviral effects of porcine interferon-alpha in serum from piglets which had been infected 19 h previously with transmissible gastroenteritis virus, and of porcine interferon-beta prepared in PK-15 cells by induction with polyinosinic:polycytidylic acid, in yield reduction assays in pig kidney cells which were treated with interferon before virus challenge, and both before and after virus challenge. The most sensitive virus to both types of interferon was vesicular stomatitis. A porcine isolate of bovine herpesvirus type 1, hemagglutinating encephalomyelitis virus and porcine enterovirus types 1 and 2 were also highly sensitive to interferon-alpha. There was little reduction in the yield of porcine parvovirus or porcine rotavirus, while swinepox, swine influenza and transmissible gastroenteritis viruses were intermediate in their sensitivity to interferon-alpha. In addition to vesicular stomatitis virus, porcine adenovirus type 3, swine influenza, hemagglutinating encephalomyelitis and porcine rotavirus were highly sensitive to interferon-beta, while swinepox, bovine herpesvirus type 1, porcine parvovirus, transmissible gastroenteritis and porcine enteroviruses were less sensitive than the above viruses to interferon-beta, although all showed significant reductions in virus yield.",,"Derbyshire, J B",,,,
,PMC,Human viral gastroenteritis.,,PMC358100,,,"During the last 15 years, several different groups of fastidious viruses that are responsible for a large proportion of acute viral gastroenteritis cases have been discovered by the electron microscopic examination of stool specimens. This disease is one of the most prevalent and serious clinical syndromes seen around the world, especially in children. Rotaviruses, in the family Reoviridae, and fastidious fecal adenoviruses account for much of the viral gastroenteritis in infants and young children, whereas the small caliciviruses and unclassified astroviruses, and possibly enteric coronaviruses, are responsible for significantly fewer cases overall. In addition to electron microscopy, enzyme immunoassays and other rapid antigen detection systems have been developed to detect rotaviruses and fastidious fecal adenoviruses in the stool specimens of both nonhospitalized patients and those hospitalized for dehydration and electrolyte imbalance. Experimental rotavirus vaccines have also been developed, due to the prevalence and seriousness of rotavirus infection. The small, unclassified Norwalk virus and morphologically similar viruses are responsible for large and small outbreaks of acute gastroenteritis in older children, adolescents, and adults. Hospitalization of older patients infected with these viruses is usually not required, and their laboratory diagnoses have been limited primarily to research laboratories.",,"Christensen, M L",,,,
,PMC,Comparison of isolation in cell culture with conventional and modified mouse antibody production tests for detection of murine viruses.,,PMC267259,,,"The sensitivity of the mouse antibody production test with intraperitoneal or intrasplenic inoculation of mice with reovirus type 3, minute virus of mice, lymphocytic choriomeningitis virus, or mouse hepatitis virus was compared with that of direct isolation in cultured cells. The mouse antibody production test for detection of mouse hepatitis virus was significantly more sensitive than virus isolation in permissive cells, but differences in sensitivity were less marked for the other three viruses. The intrasplenic route of inoculation did not yield seroconversion that occurred earlier or more consistently than that detected after intraperitoneal inoculation.",,"['de Souza, M', 'Smith, A L']",,,,
,PMC,Intrinsic resistance of feline peritoneal macrophages to coronavirus infection correlates with in vivo virulence.,,PMC247703,,,"Cats infected with virulent feline coronavirus strains develop feline infectious peritonitis, an invariably fatal, immunologically mediated disease; avirulent strains cause either clinically inapparent infection or mild enteritis. Four virulent coronavirus isolates and five avirulent isolates were assessed by immunofluorescence and virus titration for their ability to infect and replicate in feline peritoneal macrophages in vitro. The avirulent coronaviruses infected fewer macrophages, produced lower virus titers, were less able to sustain viral replication, and spread less efficiently to other susceptible macrophages than the virulent coronaviruses. Thus, the intrinsic resistance of feline macrophages may play a pivotal role in the outcome of coronavirus infection in vivo.",,"['Stoddart, C A', 'Scott, F W']",,,,
,PMC,"Processing, surface expression, and immunogenicity of carboxy-terminally truncated mutants of G protein of human respiratory syncytial virus.",,PMC247698,,,"Posttranslational processing and cell surface expression were examined for three C-terminally truncated mutants of the G protein of respiratory syncytial virus expressed from engineered cDNAs. The truncated mutants, encoded by cDNAs designated G71, G180, and G230, contained the N-terminal 71, 180, and 230 amino acids, respectively, of the 298-amino-acid G protein. To facilitate detection of G71, which reacted inefficiently with G-specific antisera, we constructed a parallel set of cDNAs, designated G71/13, G180/13, and G230/13, to encode the same truncated species with the addition of a C-terminal 13-amino-acid reporter peptide which could be detected efficiently with an antipeptide serum. G71, G180, and G230 were expressed as species of Mr 7,500, 48,000, and 51,000, respectively, compared with 84,000 for parental G protein. The proteins encoded by G180 and G230, like parental G protein, contained both N-linked and O-linked carbohydrate. Also, the protein encoded by G71/13 appeared to be O glycosylated, showing that even this highly truncated form contained the structural information required to target the protein for O glycosylation. As for parental G protein, the estimated Mrs of the proteins encoded by G180 and G230 were approximately twice the calculated molecular weight of the polypeptide chain. Experiments with monensin showed that most of this difference between the calculated and observed Mr was due to posttranslational processing in or beyond the trans-Golgi compartment, presumably owing to the addition of carbohydrate or aggregation into dimers or both. Like parental G protein, all three truncated forms accumulated abundantly at the cell surface, and in each case the C terminus was extracellular. Thus, the N-terminal 71 amino acids of the G protein contained all the structural information required for efficient membrane insertion and cell surface expression, whereas the extracellular domain was dispensable for these activities. Cotton rats were immunized with recombinant vaccinia viruses expressing the G71, G180, G230, or parental G protein to compare their abilities to induce serum antibodies and resistance to challenge virus replication. The G71 and G180 recombinants failed to induce significant levels of G-specific antibodies or resistance to challenge, whereas the immunogenicity of G230 equaled or exceeded that of parental G protein. This suggested that the C-terminal 68 amino acids of the 236-amino-acid ectodomain do not contribute to the major epitope(s) of the G protein that is involved in inducing protective immunity.",,"['Olmsted, R A', 'Murphy, B R', 'Lawrence, L A', 'Elango, N', 'Moss, B', 'Collins, P L']",,,,
,PMC,Preferred sites of recombination in poliovirus RNA: an analysis of 40 intertypic cross-over sequences.,,PMC339105,,,"The genome of poliovirus consists of a single strand of RNA approximately 7.5 kb long. Analysis of the sequences around 40 unique recombination sites reveals several features that differ significantly from those expected of randomly located sites. These features, which include a broad zone of elevated homology on the 3' side of the cross-over, support the theory that RNA recombination occurs by a template-switching mechanism during synthesis of the complementary strand, and that sites are chosen to minimise the adverse free energy change involved in switching to a heterotypic template. There is also a strong sequence bias, almost two-thirds of cross-overs, according to a computer simulation, occurring immediately after synthesis of UU. These features shed new light on the extent of base-pairing in replicative intermediate RNA, and on the mechanism of chain initiation.",,"King, A M",,,,
,PMC,Acquired hydrocephalus and hydromyelia in a cat with feline infectious peritonitis: A case report and brief review,,PMC1681069,,,"A one-year-old domestic long-haired cat was referred to the New York State College of Veterinary Medicine because of acute onset of paraparesis and hyperesthesia associated with trauma. Myelography and cerebrospinal fluid analysis revealed severe hydromyelia and myelitis, respectively. The definitive diagnosis of feline infectious peritonitis was made by histological examination at necropsy. Lesions were confined exclusively to the brain and spinal cord. Partial occlusion of the third and fourth ventricles with pyogranulomatous debris caused hydrocephalus and subsequent hydromyelia. The hydromyelia may have been the primary means of compensation for the hydrocephalus, thus masking subclinical disease.",,"['Tamke, Patricia G.', 'Petersen, Mark G.', 'Dietze, Amy E.', 'deLahunta, Alexander']",,,,
,PMC,A study of intranasally administered interferon A (rIFN-alpha 2A) for the seasonal prophylaxis of natural viral infections of the upper respiratory tract in healthy volunteers.,,PMC2249423,,,"The efficacy of interferon A (rIFN-alpha 2A), an Escherichia coli-derived interferon, in the prophylaxis of acute upper respiratory tract infection, was evaluated in a community-based double-blind placebo-controlled study in the Australian winter of 1985. The trial population of 412 healthy volunteers (190 males and 222 females, aged 18-65 years) self-administered 1.5, 3.0 and 6.0 megaunits (MU) of interferon A per day or a placebo, intranasally for 28 days. The period of study coincided with an outbreak of H3N2 influenza A (detected in 35 of the 107 acute specimens) as well as substantial numbers of respiratory syncytial virus and adenovirus infections. Rhinoviruses were isolated from only three specimens. In many cases, subjects had laboratory and clinical evidence of having had more than one respiratory tract infection during the period of the study. Viruses were detected in 54 or 107 acute specimens (49%). No statistically significant differences were noted between the various treatment groups in the incidence of laboratory-proven viral infection (virus isolation and/or antibody response). Analysis of reported symptoms indicated that blood-tinged mucus and nasal stuffiness occurred more frequently with higher doses of interferon. There appeared to be no clinical benefit from the use of interferon A in the amelioration of symptoms.",,"['Tannock, G. A.', 'Gillett, S. M.', 'Gillett, R. S.', 'Barry, R. D.', 'Hensley, M. J.', 'Herd, R.', 'Reid, A. L.', 'Saunders, N. A.']",,,,
,PMC,MHC class I and class II antigen expression in normal human corneas and in corneas from cases of herpetic keratitis.,,PMC1385568,,,"The expression of HLA class I and class II antigens in corneas from normal donors and patients with quiescent herpetic keratitis was investigated using specific monoclonal antibodies. Keratocytes from diseased corneas showed aberrant expression of HLA class I and class II (DR, DP and DQ) antigens. The expression of HLA antigens in these corneas was not associated with immune cell infiltrates or viral antigens.",,"['McBride, B W', 'McGill, J I', 'Smith, J L']",,,,
,PMC,Protease inhibitors suppress the in vitro and in vivo replication of rotavirus.,,PMC442783,,,"Rotaviruses are major causes of infectious gastroenteritis in humans and other animals. We found that a variety of protease inhibitors suppressed the replication of the SA-11 strain of rotavirus in MA-104 cell cultures. Three of these compounds, leupeptin, pentamidine, and bis (5-amidino-2-benzimidazolyl) methane (BABIM) also restricted the intestinal replication of the murine strain of rotavirus when protease inhibitor and virus were administered simultaneously to suckling mice. Repeated administration of BABIM resulted in significantly reduced levels of intestinal rotaviral antigen even if administration of the compound was begun as late as 48 h after viral inoculation. Additionally, BABIM-treated animals had significantly less intestinal replication of rotavirus than did placebo-treated controls when placed in a heavily rotavirus-contaminated environment. The use of protease inhibitors represents a novel approach to the control of this important gastrointestinal pathogen and is a potential modality for the prevention and treatment of diseases caused by other enteric viruses, for which proteolytic cleavage is necessary for efficient replication.",,"['Vonderfecht, S L', 'Miskuff, R L', 'Wee, S B', 'Sato, S', 'Tidwell, R R', 'Geratz, J D', 'Yolken, R H']",,,,
,PMC,Tumorigenic potential of a myc-containing strain of feline leukemia virus in vivo in domestic cats.,,PMC253596,,,"The oncogenic capacity of a myc-containing strain of feline leukemia virus (FeLV), termed LC-FeLV, has been examined after inoculation of the virus into neonatal kittens. Like other myc-containing strains of FeLV, LC-FeLV may induce with relatively short latency, but does not necessarily induce, thymic lymphosarcoma in viremic animals. Naturally occurring and experimentally induced tumors are T-cell lymphomas which contain clonally integrated LC-FeLV proviral DNA and which cannot readily be cultivated in vitro in the presence or absence of exogenously supplied interleukin-2. Acquisition of myc by FeLV decreases the period of latency before the appearance of tumors but does not expand the spectrum of tumors induced by FeLV alone.",,"['Levy, L S', 'Fish, R E', 'Baskin, G B']",,,,
,PMC,The E3 protein of bovine coronavirus is a receptor-destroying enzyme with acetylesterase activity.,,PMC253582,,,"In addition to members of the Orthomyxoviridae and Paramyxoviridae, several coronaviruses have been shown to possess receptor-destroying activities. Purified bovine coronavirus (BCV) preparations have an esterase activity which inactivates O-acetylsialic acid-containing receptors on erythrocytes. Diisopropyl fluorophosphate (DFP) completely inhibits this receptor-destroying activity of BCV, suggesting that the viral enzyme is a serine esterase. Treatment of purified BCV with [3H]DFP and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the proteins revealed that the E3 protein was specifically phosphorylated. This finding suggests that the esterase/receptor-destroying activity of BCV is associated with the E3 protein. Furthermore, treatment of BCV with DFP dramatically reduced its infectivity in a plaque assay. It is assumed that the esterase activity of BCV is required in an early step of virus replication, possibly during virus entry or uncoating.",,"['Vlasak, R', 'Luytjes, W', 'Leider, J', 'Spaan, W', 'Palese, P']",,,,
,PMC,Differential premature termination of transcription as a proposed mechanism for the regulation of coronavirus gene expression.,,PMC338943,,,"We propose that the different subgenomic mRNA levels of coronaviruses are controlled through differential premature termination of transcription, and are modulated by the relative strength of transcriptional initiation/blockage events. We present the complete set of sequences covering the leader encoding and intergenic regions of the MHV-A59 strain. A computer-assisted analysis of the two now complete sets of these sequences of strain IBV-M42 and MHV-A59 shows that, in contrast to the previous theory, differences amongst stabilities of intermolecular base-pairings between the leader and the intergenic regions are not sufficient to determine the mRNA gradients in both MHV and IBV infected cells. Neither can the accessibility of the interacting regions on the leader and the negative stranded genome, as revealed by secondary structure analysis, explain the mRNA levels. The nested gene organisation itself, on the other hand, could be responsible for observed mRNA levels gradually increasing with gene order. Relatively slow new initiation events at intergenic regions are proposed to block elongation of passing transcripts which, via temporary pausing, can cause premature termination of transcription. This effects longer transcripts more than shorter ones.",,"['Konings, D A', 'Bredenbeek, P J', 'Noten, J F', 'Hogeweg, P', 'Spaan, W J']",,,,
,PMC,Rapid identification of overlapping cDNA clones by Southern cross-hybridization.,,PMC338890,,,,,"['Jouvenne, P', 'Talbot, P J']",,,,
,PMC,"Drinking water source, diarrheal morbidity, and child growth in villages with both traditional and improved water supplies in rural Lesotho, southern Africa.",,PMC1350237,,,"This study examined the growth and morbidity rates of young children in relation to exclusive and non-exclusive use of improved water supplies in rural Lesotho, southern Africa. Data were collected for 247 children 60 months of age and under between July 1984 and February 1985 in 10 villages that had an improved water supply at least one year prior to investigation. Children whose families relied exclusively on the new water supply for their drinking and cooking needs grew 0.438 cm and 235 g more in six months than children whose families supplemented the new water supply with the use of contaminated traditional water for drinking and cooking. The difference in growth was greater among children over 12 months of age at the start of the evaluation than among infants. This may be explained partly by lower rates for Giardia lamblia, the most commonly identified pathogen in stools in older children. Among infants, similar rates of Campylobacter, the most commonly isolated pathogen among infants, may have prevented larger differences. Results suggest that improved drinking water supplies can benefit preschool children's health after infancy, but only if they are functioning and utilized exclusively for drinking and cooking purposes.",,"['Esrey, S A', 'Habicht, J P', 'Latham, M C', 'Sisler, D G', 'Casella, G']",,,,
,PMC,Propagation of the virus of porcine epidemic diarrhea in cell culture.,,PMC266866,,,"Porcine epidemic diarrhea virus (PEDV) was adapted to serial propagation in Vero cell cultures by adding trypsin to the medium. PEDV-infected cells showed a distinct cytoplasmic fluorescence when examined by a fluorescent-antibody-staining technique. Cytopathic effects, such as vacuolation, formation of syncytia, and fusion of cells, were detected even at passage 1 of the PEDV in Vero cells. Once adapted, the virus induced numerous syncytia containing over 100 nuclei. From virus passage 5 on, all cells forming the monolayer were fused and totally destroyed within 24 h after inoculation. Cell culture-grown PEDV had typical coronavirus morphology when viewed by electron microscopy. Attempts to propagate PEDV in several primary and secondary fetal porcine cell cultures in the presence or absence of trypsin were unsuccessful.",,"['Hofmann, M', 'Wyler, R']",,,,
,PMC,Specific interaction between coronavirus leader RNA and nucleocapsid protein.,,PMC253863,,,"Northwestern blot analysis in the presence of competitor RNA was used to examine the interaction between the mouse hepatitis virus (MHV) nucleocapsid protein (N) and virus-specific RNAs. Our accompanying article demonstrates that anti-N monoclonal antibodies immunoprecipitated all seven MHV-specific RNAs as well as the small leader-containing RNAs from infected cells. In this article we report that a Northwestern blotting protocol using radiolabeled viral RNAs in the presence of host cell competitor RNA can be used to demonstrate a high-affinity interaction between the MHV N protein and the virus-specific RNAs. Further, RNA probes prepared by in vitro transcription were used to define the sequences that participate in such high-affinity binding. A specific interaction occurs between the N protein and sequences contained with the leader RNA which is conserved at the 5' end of all MHV RNAs. We have further defined the binding sites to the area of nucleotides 56 to 65 at the 3' end of the leader RNA and suggest that this interaction may play an important role in the discontinuous nonprocessive RNA transcriptional process unique to coronaviruses.",,"['Stohlman, S A', 'Baric, R S', 'Nelson, G N', 'Soe, L H', 'Welter, L M', 'Deans, R J']",,,,
,PMC,Interactions between coronavirus nucleocapsid protein and viral RNAs: implications for viral transcription.,,PMC253862,,,"The interaction of the mouse hepatitis virus (MHV) nucleocapsid protein (N) and viral RNA was examined. Monoclonal antibody specific for N protein coimmunoprecipitated MHV genomic RNA as well as all six MHV subgenomic mRNAs found in MHV-infected cells. In contrast, monoclonal antibodies to the MHV E2 or E1 envelope glycoproteins, an anti-I-A monoclonal antibody, and serum samples from lupus patients did not immunoprecipitate the MHV mRNAs. Moreover, the anti-N monoclonal antibody did not coimmunoprecipitate vesicular stomatitis virus RNA or host cell RNA under conditions which immunoprecipitated all MHV RNAs. These data suggest a specific interaction between the N protein and the virus-specific mRNAs. Both the membrane-bound and cytosolic small MHV leader-specific RNAs of greater than 65 nucleotides long were immunoprecipitated only by anti-N monoclonal antibody. These data suggest that an N binding site is present within the leader RNA sequences at a site at least 65 nucleotides from the 5' end of genomic RNA and all six subgenomic mRNAs. The larger leader-containing RNAs originating from mRNA 1 and mRNA 6, as well as the MHV negative-stranded RNA, were also immunoprecipitated by the anti-N monoclonal antibody. These data indicate that the MHV N protein is associated with MHV-specific RNAs and RNA intermediates and may play an important functional role during MHV transcription and replication.",,"['Baric, R S', 'Nelson, G W', 'Fleming, J O', 'Deans, R J', 'Keck, J G', 'Casteel, N', 'Stohlman, S A']",,,,
,PMC,Colitis in calves: natural and experimental infection with a verotoxin-producing strain of Escherichia coli O111:NM.,,PMC1255496,,,"Verotoxin-producing Escherichia coli O111:NM were isolated from two five week old Holstein calves with dysentery. On necropsy both calves had pseudomembranous ileitis, mucohemorrhagic colitis and proctitis. Large numbers of E. coli O111:NM were isolated from the colon and lesions typical of attaching-and-effacing E. coli were evident. The isolates from both calves had identical biochemical reactions and antimicrobial resistance patterns. Oral inoculation of a four day old colostrum deprived calf with 1 x 10(10) organisms of E. coli O111:NM produced a mild, focal colitis with typical attachment and effacement lesions. We conclude that the strain of E. coli O111:NM isolated from the clinical cases has the ability to produce colitis characterized by attachment and effacement of the colonic mucosa.",,"['Schoonderwoerd, M', 'Clarke, R C', 'van Dreumel, A A', 'Rawluk, S A']",,,,
,PMC,Characterization of group II avian adenoviruses with a panel of monoclonal antibodies.,,PMC1255491,,,"The interaction between a panel of ten monoclonal antibodies and hemorrhagic enteritis virus, a group II avian adenovirus, was determined. The monoclonal antibodies reacted with all nine isolates of group II avian adenoviruses, but not with any of five types of group I avian adenoviruses. All ten monoclonal antibodies recognized antigenic determinants on the hexon protein of hemorrhagic enteritis virus when analyzed by immunoprecipitation and immunoblotting. They reacted only with the native hexon protein and not with protein denatured by sodium dodecyl sulfate or guanidine-HCl/urea treatment combined with reduction and carboxymethylation. Based on the results of competitive binding assays, the panel of monoclonal antibodies could be subdivided into two groups, which recognized different antigenic domains of the hemorrhagic enteritis virus hexon protein. The monoclonal antibodies in group 1 neutralized hemorrhagic enteritis virus infectivity while the monoclonal antibodies of group 2 did not. Group 1 consisted of eight monoclonal antibodies which could be further subdivided into subgroups 1A, 1B, 1C and 1D. The subdivision of the monoclonal antibodies was based on the degree of blocking in the competitive binding assays and differences in their ability to induce enhancement. In general, the monoclonal antibodies had a higher avidity for the virulent isolate of hemorrhagic enteritis virus than for the avirulent hemorrhagic enteritis virus isolate.",,"['van den Hurk, J V', 'van Drunen Littel-van den Hurk, S']",,,,
,PMC,Molecular cloning of complementary DNA from a pneumopathic strain of bovine viral diarrhea virus and its diagnostic application.,,PMC1255490,,,"A pneumopathic strain of bovine viral diarrhea virus was grown in cell culture and purified. Genomic ribonucleic acid was extracted, polyadenylated at the 3' end, and copied into complementary DNA after oligo-dT priming. Complementary DNA was male double stranded and cloned into the pUC9 plasmid. Approximately 200 complementary DNA clones varying in length from 0.5 to 2.5 kilobases were obtained. Hybridization assays indicated that the sequences isolated were specific for bovine viral diarrhea virus and that at least 5.5 kilobases of bovine viral diarrhea virus genome was represented in the library of complementary DNA clones, the majority of which may have originated from the 3' end of the virus genome. One cloned complementary DNA sequence was used as a 32P-labelled hybridization probe for bovine viral diarrhea virus detection. The probe hybridized with all cytopathic and noncytopathic strains of bovine viral diarrhea virus tested and was 100 times more sensitive than infectivity assays for the detection of bovine viral diarrhea virus. Hybridization did not occur with nucleic acids from bovine coronavirus, bluetongue virus, bovine adenovirus or uninfected cell cultures. Native plasmid DNA sequences, labelled with 32P, did not hybridize with bovine viral diarrhea virus ribonucleic acid.",,"['Brock, K V', 'Brian, D A', 'Rouse, B T', 'Potgieter, L N']",,,,
,PMC,Contemporary issues: diseases with a food vector.,,PMC358061,,,"Foodborne disease has become a contemporary issue. Several large, well-publicized outbreaks of foodborne disease have heightened public awareness that harmful microorganisms may be present in food and that chronic as well as acute disease may be caused by foodborne microbes. The field of food microbiology has likewise experienced a resurgence of interest. New tools, such as recombinant deoxyribonucleic acid technology and monoclonal antibody production, used to elucidate microbial virulence factors have facilitated identification of disease-causing microbes once thought to be harmless and demonstrated the complexity of individual virulence mechanisms previously considered to be well understood. Foodborne pathogens are also causing disease via some surprising food vectors, such as chopped, bottled garlic and sauteed onions. In addition to acute gastrointestinal disturbances, certain microorganisms may, through complex interactions with the human immune response, cause chronic diseases that affect several major organ systems. These microbes are serving as models in studies of molecular mimicry and genetic interrelatedness of procaryotes and eucaryotes. Other recently recognized attributes of foodborne microorganisms, such as the heat shock phenomenon and the possible nonculturability of some bacteria, may affect their ability to cause disease in humans. Because foodborne disease is a major cause of morbidity and mortality, the study of these diseases and their causative microorganisms presents a unique challenge to many professionals in the subdisciplines of microbiology, epidemiology, and clinical medicine.",,"['Archer, D L', 'Young, F E']",,,,
,PMC,Determination of antibody response to influenza virus surface glycoproteins by kinetic enzyme-linked immunosorbent assay.,,PMC266811,,,"We modified an existing enzyme-linked immunosorbent assay (ELISA) to be able to use new spectrophotometers which can measure the rate of color development in microtiter wells. This new kinetic-based ELISA (KELISA) required only a single dilution of specimen rather than the multiple dilutions required with endpoint ELISA. In addition, 10- to 100-fold-less specimen was required to perform the KELISA than the ELISA. The level of serum or nasal wash antibody against surface glycoproteins of influenza A or influenza B viruses determined by KELISA was reproducible and correlated highly with the results of endpoint ELISA or hemagglutination inhibition tests. The difference between the KELISA rates, which indicated than an antibody response to infection had occurred, was defined and was analogous to a 2.2-fold rise in titer for serum and a 3.4-fold rise in titer for nasal wash determined by endpoint ELISA. The KELISA was similar to endpoint ELISAs in its ability to detect rises in antibody level in paired serum or nasal wash specimens obtained from volunteers who received live attenuated influenza A reassortant virus vaccines. By eliminating the need for multiple dilutions, the use of KELISA offers the advantage of increasing the number of assays that can be performed by the same personnel compared with endpoint ELISA, while it maintains sensitivity and specificity.",,"['Snyder, M H', 'Banks, S', 'Murphy, B R']",,,,
,PMC,Discontinuous transcription generates heterogeneity at the leader fusion sites of coronavirus mRNAs.,,PMC253535,,,"Coronavirus mRNA is synthesized by a discontinuous transcription process, which involves a free leader RNA species. As a result, each virus-specific mRNA contains an identical leader RNA derived from the 5', end of the genomic RNA. In this study, we demonstrate by primer extension studies that the leader-fusion sites on a given species of coronavirus subgenomic mRNA are heterogeneous. The heterogeneity was due to variation in the number of pentanucleotide (UCUAA) repeats present at the leader fusion site. This pentanucleotide repeat region was complementary between the free leader RNA and the transcription start sites on the template RNA. This result suggests that the discontinuous transcription of coronavirus mRNAs occurs within the complementary sequences localized in two different RNA segments and that RNA joining occurs at variable sites.",,"['Makino, S', 'Soe, L H', 'Shieh, C K', 'Lai, M M']",,,,
,PMC,Inducible expression of herpes simplex virus type 2 glycoprotein gene gG-2 in a mammalian cell line.,,PMC253509,,,"The gG-2 glycoprotein gene of herpes simplex virus type 2 (HSV-2) was cloned into the mammalian expression vector pMSG under the control of the inducible mouse mammary tumor virus promoter. Transfection of this cloned gG-2 construct into NIH 3T3 cells resulted in the stable expression of gG-2 upon induction with dexamethasone. In addition, the 104,000-molecular-weight (104K) and 72K gG-2 precursors as well as the 34K secreted component were generated in the transformed cells. The synthesis of gG-2 in these transformed cells appeared to follow the same cleavage-processing pathway as gG-2 synthesis during an HSV-2 infection. These results indicate that the processing of gG-2 can occur in the absence of an HSV-2 infection.",,"['Su, H K', 'Courtney, R J']",,,,
,PMC,Expression of Leaf Nitrate Reductase Genes from Tomato and Tobacco in Relation to Light-Dark Regimes and Nitrate Supply,,PMC1055586,,,"The influence of light-dark cycles and nitrate supply on nitrate reductase (NR) mRNA levels was studied in two plant species, tobacco (Nicotiana tabacum) and tomato (Lycopersicon esculentum) using specific NR DNA probes. In the same series of experiments, changes in the levels of NR protein (NRP) by enzyme-linked immunosorbent assay and changes in the level of NADH-nitrate reductase activity (NRA) were also followed. During a light-dark cycle, it was found that in both tomato and tobacco, NR mRNA accumulation increased rapidly during the dark period and reached a maximum at the beginning of the day, while NRP reached a peak 2 and 4 hours after mRNA peaked, for tomato and tobacco, respectively. At the end of the day, the amount of mRNA was decreased by a factor of at least 100 compared to sunrise in both species. These results demonstrate that light is involved, although probably not directly, in the regulation of the NR gene expression at the mRNA level. The peak of NRA in tobacco coincided with the peak in NR mRNA accumulation (i.e. sunrise), whereas in tomato the peak of NRA was approximately 5 to 6 hours after sunrise. There is no obvious correlation between NRP and NRA levels during the day. In nitrogen starvation experiments, a rapid decrease of NRP and NRA was detected, while NR mRNA levels were not significantly altered. Upon nitrate replenishment, nitrogen-starved plants accumulated NR mRNA rapidly. These results suggest that the availability of nitrogen affects the expression of NR activity at the transcriptional as well as at the post-transcriptional levels.",,"['Galangau, Fabienne', 'Daniel-Vedele, Françoise', 'Moureaux, Thérèse', 'Dorbe, Marie-France', 'Leydecker, Marie-Thérèse', 'Caboche, Michel']",,,,
,PMC,Adult onset Still's disease and viral infections.,,PMC1003594,,,"Several micro-organisms, especially viruses, have been associated with juvenile and adult onset Still's disease. In the present study a search for probable triggering viral infections in five consecutive patients with early, active adult onset Still's disease has been made. In one patient echovirus 7 was identified as a probable triggering agent. Evidence of infection with this virus was acquired by virus cultures and serological tests. In two patients the illness was probably initiated by a rubella reinfection. Both had initially high stable monospecific IgG antibody titres but no IgM antibodies to this virus. In the remaining two cases no particular triggering viral infection could be designated. Evidence of a viral infection was thus found in three of these five patients. Adult onset Still's disease may represent a reaction pattern to certain infections.",,"['Wouters, J M', 'van der Veen, J', 'van de Putte, L B', 'de Rooij, D J']",,,,
,PMC,New Products,,PMC1680831,,,,,,,,,
,PMC,Comparison of nine commercial immunoassays for the detection of rotavirus in fecal specimens.,,PMC266685,,,"One hundred fecal specimens obtained from patients with acute gastroenteritis were tested for rotavirus with nine commercial immunoassays to evaluate the sensitivity, specificity, predictive value, and diagnostic accuracy of these assays. Kits evaluated included two monoclonal antibody-based enzyme immunoassays (EIAs) (Rotaclone and Pathfinder Rotavirus), three polyclonal antibody-based EIAs (Rotavirus Immunoassay, Rotazyme II, and Wellcozyme Rotavirus), and four latex agglutination assays (Rotastat, Virogen Rotatest, Meritec-Rotavirus, and The Wellcome Latex Test). Thirty-eight of the 100 specimens were found to contain rotavirus by a reference microplate EIA. The accuracy of the reference assay was determined by RNA electrophoresis and a blocking assay on discordant specimens. The two monoclonal antibody EIAs had superior sensitivities (100%) and identified two positive specimens which were negative by the reference method but positive by the blocking assay. Among the polyclonal EIAs, all had sensitivities of greater than 90%, but specificities were variable; Rotazyme II, with a specificity of 50%, showed considerable discrepancy from other polyclonal EIAs. The latex tests had sensitivities ranging from 70 to 90% and specificities of 80 to 100%. Latex agglutination tests were more rapid than EIAs and did not require expensive equipment. The final choice of assay system will depend on the cost, speed, and accuracy requirements of the clinical laboratory.",,"['Dennehy, P H', 'Gauntlett, D R', 'Tente, W E']",,,,
,PMC,Spontaneous production of interleukin-2 and interleukin-3 by spleen cells from mice infected with mouse hepatitis virus type 4.,,PMC253478,,,"Spleen cells from mice, 4 to 60 days after infection with mouse hepatitis virus type 4, produced interleukin-2, as well as interleukin-3, in the absence of exogenous stimulants in vitro. This unique lymphokine production by mouse hepatitis virus type 4 infection was controlled by host genes.",,"['Kyuwa, S', 'Yamaguchi, K', 'Hayami, M', 'Hilgers, J', 'Fujiwara, K']",,,,
,PMC,In vivo and in vitro models of demyelinating disease: efficiency of virus spread and formation of infectious centers among glial cells is genetically determined by the murine host.,,PMC253460,,,"Resistance or susceptibility of various mouse strains to central nervous system disease caused by different strains of coronavirus is well known. Data from the present study draw attention to an additional, genetically determined mechanism controlling CV infections. The resistance to A59 and JHM virus (JHMV) associated with SJL mice was maintained in explanted glial cultures which, by contrast, fully supported a productive infection by the serorelated mouse hepatitis virus type 3. A comparative analysis of the infectious process in glial cell explants from SJL and CD.1 mice helped to define the stage at which restriction is manifested. Cultures of oligodendrocytes and astrocytes from these strains of mice were challenged with JHMV or mouse hepatitis virus type 3, and cell-virus interactions were monitored, including adsorption, uptake of inoculum, transcription, and cell-to-cell dissemination. The sequence of early events from adsorption to genome activation occurred with about equal efficiency with both viruses and genetically different cells, indicating that SJL resistance is not due to any deficiency in specific receptors or penetration of the inoculum or general expression of viral functions. However, intercellular spread of the infection was restricted in SJL glial cells owing to an as yet undefined component. Since cells from (SJL x CD.1)F1 mice were fully susceptible to JHMV, resistance to virus spread must be due to a deficiency in some factor, perhaps a proteolytic activity necessary for dissemination.",,"['Wilson, G A', 'Dales, S']",,,,
,PMC,Formalin inactivation of the lactate dehydrogenase-elevating virus reveals a major neutralizing epitope not recognized during natural infection.,,PMC253439,,,"Five hybridomas that secrete monoclonal antibodies which neutralize the infectivity of lactate dehydrogenase-elevating virus (LDV) were isolated from BALB/c mice primed with Formalin-inactivated LDV. Competition analyses indicated that all five neutralizing monoclonal antibodies recognize contiguous, if not identical, epitopes on the envelope glycoprotein of LDV (VP-3) which are not recognized by nonneutralizing VP-3-specific monoclonal antibodies isolated from the same fusion. Despite the presence of neutralizing activity, polyclonal anti-LDV antibodies obtained from persistently infected mice did not compete for binding to LDV with four of the five neutralizing monoclonal antibodies tested. The results indicate that the envelope glycoprotein of LDV possesses a major neutralizing epitope which is poorly recognized, if at all, by mice during a natural infection but is rendered immunogenic by Formalin inactivation of the virus. The epitope was also not immunogenic in a rabbit, since its polyclonal LDV-neutralizing antibodies did not inhibit binding of the mouse monoclonal antibodies to LDV. Passive immunization with the neutralizing monoclonal antibodies did not protect mice from LDV infection and did not alter the course of infection. Neutralizing monoclonal antibodies have been used to select a neutralization escape variant by a novel combination of in vitro and in vivo isolation.",,"['Harty, J T', 'Plagemann, P G']",,,,
,PMC,Viral respiratory tract infection and exacerbations of asthma in adult patients.,,PMC461455,,,"The role of viral respiratory tract infections in acute exacerbations of asthma was studied prospectively in 31 patients with atopic asthma aged 15-56 years. Patients recorded symptom scores for asthma and peak expiratory flow rate daily for 11 months. In addition, they reported for detailed clinical, functional, and virological study every four weeks and as soon as possible after the onset of worsening asthma or symptoms suggesting a respiratory tract infection. Thirty viral identifications were made, of which 18 (60%) were associated with an exacerbation of asthma. Viral respiratory tract infection was identified in 18 (10%) of the 178 exacerbations of asthma, and in 10 (36%) of the 28 severe exacerbations. The frequency of viral identifications in 16 non-asthmatic, control subjects during the same period was similar. It is concluded that viral respiratory tract infections may cause or be associated with exacerbations of asthma in adults, and that they are an important factor in severe exacerbations.",,"['Beasley, R', 'Coleman, E D', 'Hermon, Y', 'Holst, P E', ""O'Donnell, T V"", 'Tobias, M']",,,,
,PMC,Vaccination against lethal coronavirus-induced encephalitis with a synthetic decapeptide homologous to a domain in the predicted peplomer stalk.,,PMC253743,,,"A surface probability method was used to select a decapeptide homologous to residues 993 to 1002 of the peplomer protein E2 of murine hepatitis virus strain JHM, a neurotropic coronavirus. This sequence of amino acids corresponded to a minor peak on a hydrophilicity plot. Immunization of mice with the chemically synthesized peptide coupled to keyhole limpet hemocyanin elicited high levels of neutralizing antibody and protected against lethal virus challenge. Protection correlated with a critical level of antipeptide antibody, which could be reached after a single inoculation. These results suggest that an appropriate antibody response to a highly restricted, surface-exposed domain of this viral protein is critical in determining the outcome of infection of the central nervous system. This sequence is located in the C-terminal fifth of the E2 peplomers, between two predicted coiled-coil structures.",,"['Talbot, P J', 'Dionne, G', 'Lacroix, M']",,,,
,PMC,Sequence and organization of barley yellow dwarf virus genomic RNA.,,PMC336850,,,"The nucleotide sequence of the genomic RNA of barley yellow dwarf virus, PAV serotype was determined, except for the 5'-terminal base, and its genome organization deduced. The 5,677 nucleotide genome contains five large open reading frames (ORFs). The genes for the coat protein (1) and the putative viral RNA-dependent RNA polymerase were identified. The latter shows a striking degree of similarity to that of carnation mottle virus (CarMV). By comparison with corona- and retrovirus RNAs, it is proposed that a translational frameshift is involved in expression of the polymerase. An ORF encoding an Mr 49,797 protein (50K ORF) may be translated by in-frame readthrough of the coat protein stop codon. The coat protein, an overlapping 17K ORF, and a 3'6.7K ORF are likely to be expressed via subgenomic mRNAs.",,"['Miller, W A', 'Waterhouse, P M', 'Gerlach, W L']",,,,
,PMC,Experimental sialodacryoadenitis virus infection in athymic CD-1 mice.,,PMC1255465,,,"The purpose of the study was to investigate the susceptibility of nude mice to sialodacryoadenitis virus. Young adult male CD-1 nude mice were inoculated intranasally with virus, killed at 2, 4, 6, 8, 10 and 20 days postinoculation and examined for virus-induced lesions in tissues including respiratory tract. Inoculated and control mice were examined by virus isolation and serology. In a companion study, male Wistar rats were inoculated intranasally with the same inoculum, and examined by histopathology, immunofluorescence microscopy and serology. In virus-inoculated mice, lesions were minimal in the lower respiratory tract, and were absent in other tissues. Virus was isolated from the lower respiratory tract in animals sampled at six or eight days postinoculation. Antiviral antibody was not detected in sera from inoculated and control mice. Virus-associated lesions and antibodies were readily detected in rats following inoculation. Based on this study, there is no evidence that inadvertent exposure to sialodacryoadenitis virus should pose a threat to CD-1 nude mice, and their susceptibility to the disease appears to be similar to that reported in euthymic CD-1 mice.",,"['Percy, D H', 'Bond, S J', 'MacInnes, J I', 'Descôteaux, J P']",,,,
,PMC,Clinical laboratory applications of monoclonal antibodies.,,PMC358053,,,"Monoclonal antibody (MAb) technology is well recognized as a significant development for producing specific serologic reagents to a wide variety of antigens in unlimited amounts. These reagents have provided the means for developing a number of highly specific and reproducible immunological assays for rapid and accurate diagnosis of an extensive list of diseases, including infectious diseases. The impact that MAbs have had in characterizing infectious disease pathogens, as well as their current and future applications for use in clinical microbiology laboratories, is reviewed. In addition, the advantages (and disadvantages) of the use of MAbs in a number of immunoassays, such as particle agglutination, radioimmunoassays, enzyme-linked immunosorbent assays, immunofluorescent-antibody assays, and immunohistology, are explored, including the use of these reagents in novel test system assays. Also, nucleic acid probe technology is compared with the use of MAbs from the perspective of their respective applications in the diagnosis of infectious disease agents. There is no question that hybridoma technology has the potential to alter significantly the methods currently used in most clinical microbiology laboratories.",,"['Payne, W J', 'Marshall, D L', 'Shockley, R K', 'Martin, W J']",,,,
,PMC,Multiple autoantibodies following cytomegalovirus infection: virus distribution and specificity of autoantibodies.,,PMC1385049,,,"Multiple autoantibodies were found in the sera of BALB/c, C57BL/10 and C3H mice following mouse cytomegalovirus (MCMV) infection. The complex pattern of intra-organ, intratissue and intracellular reactivity observed by immunoperoxidase histochemistry suggested that many autoantibodies of varying specificities were elicited. This evidence from immunoperoxidase histochemistry was confirmed by immunoblot, where autoantibodies binding to polypeptides of a variety of sizes and tissues of origin were observed. In addition to these central findings, the tissue and organ distribution of MCMV in three mouse strains of differing genetic resistance were described. No correlation was found between the distribution of virus and the tissue and organ specificity of the autoantibodies produced following infection. Inflammatory responses accompanied MCMV infection in a number of tissues. In BALB/c mice, myocarditis and salivary gland inflammation were evident at Day 56 post-infection in the absence of MCMV, but in the presence of autoantibodies to cardiac muscle and salivary duct epithelium. This model for virus-induced autoimmunity can be applied to studies of the relationship between virus infection, autoimmunity and disease.",,"['Bartholomaeus, W N', ""O'Donoghue, H"", 'Foti, D', 'Lawson, C M', 'Shellam, G R', 'Reed, W D']",,,,
,PMC,Establishment of cytotoxic T-cell clones specific for cells infected with mouse hepatitis virus.,,PMC253411,,,Mouse hepatitis virus (MHV)-specific T-lymphocyte clones were established from MHV-infected BALB/c mice. They expressed Thy1 and Lyt2 antigens but lacked L3T4 and NK1 antigens. The clones killed MHV-infected but not uninfected or influenza virus-infected J774.1 cells. The specificity was further defined by a cold-target competition test.,,"['Yamaguchi, K', 'Kyuwa, S', 'Nakanaga, K', 'Hayami, M']",,,,
,PMC,Human hepatitis delta antigen is a nuclear phosphoprotein with RNA-binding activity.,,PMC253398,,,"The genetic origin, structure, and biochemical properties of the delta antigen (HDAg) of a human hepatitis delta virus (HDV) were investigated. A cDNA fragment containing the open reading frame encoding the HDAg was transcribed into RNA and used for in vitro translation in rabbit reticulocyte lysates. The HDAg open reading frame was also inserted into an expression vector containing a simian virus 40 T-antigen promoter and expressed into COS 7 cells. In both systems, a protein species of 26 kilodaltons was synthesized from this open reading frame and could be specifically immunoprecipitated with antisera obtained from patients with delta hepatitis. A similar protein was also synthesized from antigenomic-sense monomeric HDV RNA in both systems, although the efficiency of translation was lower than that of the isolated open reading frame. This protein was found to be phosphorylated at the serine residues. Immunoperoxidase studies with anti-HDV sera demonstrated that the HDAg was expressed mainly in the nuclei of the transfected COS 7 cells. Moreover, the HDAg was shown to bind the genomic RNA of HDV. These studies indicate that HDAg is encoded by the antigenomic-sense RNA of HDV and is a nuclear phosphoprotein associated with an RNA-binding activity.",,"['Chang, M F', 'Baker, S C', 'Soe, L H', 'Kamahora, T', 'Keck, J G', 'Makino, S', 'Govindarajan, S', 'Lai, M M']",,,,
,PMC,Occupational asthma in a mineral analysis laboratory.,,PMC1009616,,,"An epidemic of symptoms suggestive of occupational asthma in workers in a mineral analysis laboratory necessitating exposure to vapours of hydrochloric, hydrofluoric, nitric, perchloric, and sulphuric acid solutions was investigated. Variable airflow obstruction was confirmed by serial measurement of FEV1 in two subjects who showed 18% and 22% fall in FEV1 during a workshift. Of a workforce of 21 laboratory staff, 20 took part in a study of ventilatory capacity and bronchial reactivity. All but one subject had normal ventilatory capacity but five had bronchial hyperreactivity (PC20 less than or equal to 8 mg/ml histamine). Four of the five with hyperreactivity had a history of chest tightness at work whereas only two subjects with chest tightness had PC20 greater than 8 mg/ml (p less than 0.01). Other work related symptoms were cough (two subjects) and breathlessness (three subjects). Four of the subjects with bronchial hyperreactivity were atopic, suggesting that hyperreactivity may have predated exposure to irritant material at work and resulted in their being susceptible to the development of symptoms and raises the possibility of identifying susceptible subjects by preplacement examination. In two of these subjects, however, bronchial reactivity has returned to normal after 205 and 376 days away from work, suggesting that bronchial inflammation resulted from occupational exposure to acid vapours.",,"['Musk, A W', 'Peach, S', 'Ryan, G']",,,,
,PMC,"New Concepts in the Pathogenesis, Diagnosis and Control of Diseases Caused by the Bovine Viral Diarrhea Virus",,PMC1680792,,,"The new information on the pathogenesis and epidemiology of mucosal disease of cattle is reviewed. It is now known that clinical mucosal disease occurs only in cattle which were infected with a pestivirus in early gestation and were born with persistent viral infection and specific immunotolerance. These animals may be clinically normal at birth but may develop fatal mucosal disease, perhaps following superinfection with another pestivirus, usually between 6 and 24 months of age. They may also remain clinically normal indefinitely and breed successfully. The progeny from persistently infected females will similarly be persistently viremic, and maternal families of such animals may be established. Congenital defects may occur when infection of the fetus occurs in mid-gestation. Although fetuses may be infected in utero in late gestation, the infections do not persist, the fetuses develop antibodies, and they appear to suffer no ill-effects. Postnatal infection can result in subclinical disease (bovine viral diarrhea) with a normal immune response; the virus may also be responsible for enhanced susceptibility to other infections, diarrhea in newborn calves, and reproductive failure. Prevention of the economically important diseases caused by the virus is dependent upon the identification and elimination of persistently viremic animals, which are reservoirs of infection, and the vaccination of immunocompetent females at least three weeks before breeding. However, because of serotypic differences between strains, there is some doubt whether vaccination will reliably provide protection against the transplacental fetal infections that are important in the pathogenesis of this disease. There is no substantial evidence to warrant the vaccination of feedlot cattle.",,"['Radostits, Otto M.', 'Littlejohns, Ian R.']",,,,
,PMC,RNA recombination of murine coronaviruses: recombination between fusion-positive mouse hepatitis virus A59 and fusion-negative mouse hepatitis virus 2.,,PMC253283,,,"It has previously been shown that the murine coronavirus mouse hepatitis virus (MHV) undergoes RNA recombination at a relatively high frequency in both tissue culture and infected animals. Thus far, all of the recombination sites had been localized at the 5' half of the RNA genome. We have now performed a cross between MHV-2, a fusion-negative murine coronavirus, and a temperature-sensitive mutant of the A59 strain of MHV, which is fusion positive at the permissive temperature. By selecting fusion-positive viruses at the nonpermissive temperature, we isolated several recombinants containing multiple crossovers in a single genome. Some of the recombinants became fusion negative during the plaque purification. The fusion ability of the recombinants parallels the presence or absence of the A59 genomic sequences encoding peplomers. Several of the recombinants have crossovers within 3' end genes which encode viral structural proteins, N and E1. These recombination sites were not specifically selected with the selection markers used. This finding, together with results of previous recombination studies, indicates that RNA recombination can occur almost anywhere from the 5' end to the 3' end along the entire genome. The data also show that the replacement of A59 genetic sequences at the 5' end of gene C, which encodes the peplomer protein, with the fusion-negative MHV-2 sequences do not affect the fusion ability of the recombinant viruses. Thus, the crucial determinant for the fusion-inducing capability appears to reside in the more carboxyl portion of the peplomer protein.",,"['Keck, J G', 'Soe, L H', 'Makino, S', 'Stohlman, S A', 'Lai, M M']",,,,
,PMC,Sialic acids on the surface of caprine arthritis-encephalitis virus define the biological properties of the virus.,,PMC253281,,,"The lentivirus caprine arthritis-encephalitis virus (CAEV) is a pathogen of goats. It is transmitted in milk and causes a persistent infection in goats, which often fail to produce neutralizing antibodies to the virus. Native CAEV particles are remarkably resistant to digestion with proteinase K and are neutralized extremely slowly by immune sera. Our studies showed that the virus particles are heavily sialylated. Studies with highly specific sialyltransferase enzymes identified penultimate carbohydrate linkages typical of O- and N-linked oligosaccharides on the virus and suggested that the virus may be more heavily sialylated on O-linked than on N-linked oligosaccharides. Removal of sialic acids from the virus by neuraminidase treatment did not reduce infectivity of the particles. However, desialylation rendered the virus more susceptible to proteolysis by proteinase K. Desialylation also enhanced the kinetics of neutralization of the virus by goat antibodies. These results suggest that the carbohydrates on the viral surface are important both in protecting viral proteins from digestion by proteases and in protecting the virus from rapid neutralization by antibodies.",,"['Huso, D L', 'Narayan, O', 'Hart, G W']",,,,
,PMC,Human and bovine coronaviruses recognize sialic acid-containing receptors similar to those of influenza C viruses.,,PMC280463,,,"Human coronavirus OC43 and bovine coronavirus elute from agglutinated chicken erythrocytes when incubated at 37 degrees C, suggesting the presence of a receptor-destroying enzyme. Moreover, bovine coronavirus exhibits an acetylesterase activity in vitro using bovine submaxillary mucin as substrate similar to the enzymatic activity found in influenza C viruses. Furthermore, pretreatment of erythrocytes with either influenza C virus or bovine coronavirus eliminates subsequent binding and agglutination by either coronaviruses or influenza C virus, whereas binding of influenza A virus remains intact. In addition, hemagglutination by coronaviruses can be inhibited by pretreatment of erythrocytes with Arthrobacter ureafaciens or Clostridium perfringens neuraminidase or by addition of sialic acid-containing gangliosides. These results suggest that, like influenza C viruses, human coronavirus OC43 and bovine coronavirus recognize O-acetylated sialic acid or a similar derivative as cell receptor.",,"['Vlasak, R', 'Luytjes, W', 'Spaan, W', 'Palese, P']",,,,
,PMC,"The response of the rat tracheal epithelium to ozone exposure. Injury, adaptation, and repair.",,PMC1880599,,,"Although acute ozone (O3) exposure injures tracheal epithelium, the response of the tracheal epithelium to prolonged O3 exposure, and the degree of repair following cessation of exposure have not been previously reported. The purpose of this experiment was to characterize the morphologic response of rat tracheal epithelium to acute (3 days) and prolonged (60 days) exposure to 0.96 ppm O3 as well as to evaluate repair in a 7- and 42-day post-60-day exposure period. Quantitative light- and electron-microscopic evaluation and thymidine labeling indices showed that after 3 days of O3 exposure there was ciliary damage, cell necrosis, an increased density of intermediate cells, and an elevated thymidine labeling index. Following 60 days of exposure, the only major change from controls was the presence of ciliated cells with uniformly short cilia. Tracheal superoxide dismutase levels did not differ between control and 60-day exposure groups. Our findings suggest that the tracheal epithelium adapts to prolonged ozone exposure with the exception of cilia formation in ciliated cells. Complete epithelial recovery occurred by 42 days after exposure.",,"['Nikula, K. J.', 'Wilson, D. W.', 'Giri, S. N.', 'Plopper, C. G.', 'Dungworth, D. L.']",,,,
,PMC,New Products,,PMC1680625,,,,,,,,,
,PMC,Minus-strand RNA synthesis in the spinal cords of mice persistently infected with Theiler's virus.,,PMC253240,,,"Theiler's virus, a murine picornavirus, causes a chronic neurological disease characterized by primary demyelination in SJL/J mice. The lesions are very reminiscent of those of multiple sclerosis. Theiler's virus persists in oligodendrocytes and to a lesser extent in astrocytes and macrophages throughout the disease. Viral RNA and capsid protein syntheses are minimal in these cells. This restriction could play a central role in the mechanism of virus persistence. By quantitating plus- and minus-strand RNAs in infected central nervous system cells, we showed that RNA replication was blocked at the level of minus-strand RNA synthesis.",,"['Cash, E', 'Chamorro, M', 'Brahic, M']",,,,
,PMC,In vivo RNA-RNA recombination of coronavirus in mouse brain.,,PMC253235,,,"RNA-RNA recombination between different strains of the murine coronavirus mouse hepatitis virus (MHV) occurs at a very high frequency in tissue culture. To demonstrate that RNA recombination may play a role in the evolution and pathogenesis of coronaviruses, we sought to determine whether MHV recombination could occur during replication in the animal host of the virus. By using two selectable markers, i.e., temperature sensitivity and monoclonal antibody neutralization, we isolated several recombinant viruses from the brains of mice infected with two different strains of MHV. The recombination frequency was very high, and recombination occurred at multiple sites on the viral RNA genome. This finding suggests that RNA-RNA recombination may play a significant role in natural evolution and neuropathogenesis of coronaviruses.",,"['Keck, J G', 'Matsushima, G K', 'Makino, S', 'Fleming, J O', 'Vannier, D M', 'Stohlman, S A', 'Lai, M M']",,,,
,PMC,Chemotherapy of rhinovirus colds.,,PMC172192,,,,,"['Sperber, S J', 'Hayden, F G']",,,,
,PMC,Immunofluorescence of bovine virus diarrhea viral antigen in white blood cells from experimentally infected immunocompetent calves.,,PMC1255445,,,A study to evaluate the detection of bovine virus diarrhea viral antigen using immunofluorescence testing of white blood cells was conducted. Five colostrum-deprived calves were inoculated intravenously with a cytopathic strain of the virus. Lymphocyte and buffy coat smears were prepared daily for direct immunofluorescent staining for detection of antigen. Lymphocytes were separated from heparinized blood using a Ficoll density procedure. Buffy coat smears were prepared from centrifuged blood samples collected using ethylenediaminetetraacetic acid as an anticoagulant. Bovine viral diarrhea virus antigen was detected by immunofluorescence between 3 and 11 days postinfection in lymphocyte smears and 3 to 12 days postinfection in buffy coat smears. Isolation of virus from both lymphocytes and buffy coat preparations correlated with detection of immunofluorescence. Serum neutralizing antibody to bovine virus diarrhea virus was detected on day 10 postinfection. Buffy coat smears were as sensitive as lymphocyte smears for the detection of antigen by immunofluorescence. It appeared that immunofluorescent staining of white blood cells was an effective method of detecting bovine virus diarrhea viral antigen.,,"['Bezek, D M', 'Baker, J C', 'Kaneene, J B']",,,,
,PMC,Vaccinia virus late transcripts generated in vitro have a poly(A) head.,,PMC454454,,,A cell free system mediating accurate transcription of vaccinia virus genes was established using lysates of cells in the late phase of infection. Vaccinia late genes are faithfully transcribed in this extract whereas cellular pol II and pol III promoters are not recognized. The late viral transcripts contain a poly(A) head of approximately 35 nt at the 5' end which is not co-linearly encoded in the externally added template. The transcripts obtained in vitro are indistinguishable from the mature in vivo RNAs. The poly(A) head is synthesized de novo and its formation appears to be directly coupled to the transcription of the gene. The synthesis of the poly(A) head transcripts in vitro is consistent with a proposed slippage model.,,"['Schwer, B', 'Stunnenberg, H G']",,,,
,PMC,A three-year diagnostic and epidemiological study on viral infantile diarrhoea in Rome.,,PMC2249227,,,"Rotavirus infection was demonstrated in 168 (29.3%) of 573 children hospitalized for acute diarrhoea in Rome between January 1982 and December 1984. Laboratory diagnosis of these infections was made by transmission electron microscopy and enzyme immunoassay techniques with an overall agreement of 91.3%. Astroviruses, adenoviruses and small round viruses were detected in the faeces of 36 patients (6.4%). Whereas in 1982 rotavirus positive patients were clustered in the winter and following spring, in the following years cases were recorded all year round. The median age of patients with rotavirus infections was 17, 10 and 11.5 months in 1982, 1983 and 1984, respectively. In addition, a smaller number of rotavirus positive cases were admitted in 1983 when compared to those admitted during the previous as well as the subsequent years. It is suggested that a herd immunity was induced in the population by epidemic spread of rotavirus in the first half of 1982.",,"['Donelli, G.', 'Ruggeri, F. M.', 'Tinari, A.', 'Marziano, M. L.', 'Menichella, D.', 'Caione, D.', 'Concato, C.', 'Rocchi, G.', 'Vella, S.']",,,,
,PMC,Lacteal immunity to enteric cryptosporidiosis in mice: immune dams do not protect their suckling pups.,,PMC259340,,,"The susceptibilities of passively immunized principal and nonimmunized control suckling mice to orogastric challenge with Cryptosporidium parvum oocysts were compared. Principals were suckled by dams that had recovered from C. parvum infection. Controls were suckled by dams reared free of C. parvum infection. Principals and controls were equally susceptible to challenge. Principals were susceptible even when their dams were hyperimmunized by oral and parenteral booster inoculations with C. parvum oocysts. Immune dams produced serum antibody against C. parvum, while nonimmune dams did not. Anti-cryptosporidia immunoglobulin G (IgG) and IgA were demonstrated in whey extracted from the stomachs of principals that had suckled immune dams but not in whey extracted from the stomachs of controls. It was concluded that passive lacteal immunity is not an efficient means of protection against cryptosporidiosis in mice. As in other coccidian infections, protective immunity against cryptosporidiosis may depend more on immune cells than on antibody.",,"['Moon, H W', 'Woodmansee, D B', 'Harp, J A', 'Abel, S', 'Ungar, B L']",,,,
,PMC,Comparison of Track XI fluorometric immunoassay with Bio-EnzaBead enzyme-linked immunosorbent assay for detection of serum antibody to mouse hepatitis virus.,,PMC266335,,,"The Track XI system (Microbiological Associates, Bethesda, Md.) was compared with the Bio-EnzaBead assay (Organon Teknika, Durham, N.C.) for the detection of antibody to mouse hepatitis virus (MHV). Strain A/J mice were inoculated intranasally with MHV type 3. Sera were collected at 1, 2, 4, and 9 weeks postinoculation and tested. Individual serum samples were retested twice by each method. The results suggested that the Track XI system was more sensitive and reliable than the Bio-EnzaBead assay in detecting antibody to MHV type 3 in individual serum samples from A/J mice.",,"['La Regina, M C', 'Lonigro, J', 'Woods, L', 'Hall, W C', 'Doyle, R E']",,,,
,PMC,O-linked glycosylation of retroviral envelope gene products.,,PMC253661,,,"Treatment of [3H]glucosamine-labeled Friend mink cell focus-forming virus (FrMCF) gp70 with excess peptide:N-glycanase F (PNGase F) resulted in removal of the expected seven N-linked oligosaccharide chains; however, approximately 10% of the glucosamine label was retained in the resulting 49,000-Mr (49K) product. For [3H]mannose-labeled gp70, similar treatment led to removal of all the carbohydrate label from the protein. Prior digestion of the PNGase F-treated gp70 with neuraminidase resulted in an additional size shift, and treatment with O-glycanase led to the removal of almost all of the PNGase F-resistant sugars. These results indicate that gp70 possesses sialic acid-containing O-linked oligosaccharides. Analysis of intracellular env precursors demonstrated that O-linked sugars were present in gPr90env, the polyprotein intermediate which contains complex sugars, but not in the primary translation product, gPr80env, and proteolytic digestion studies allowed localization of the O-linked carbohydrates to a 10K region near the center of the gp70 molecule. Similar substituents were detected on the gp70s of ecotropic and xenotropic murine leukemia viruses and two subgroups of feline leukemia virus, indicating that O-linked glycosylation is a conserved feature of retroviral env proteins.",,"['Pinter, A', 'Honnen, W J']",,,,
,PMC,Expression of the Hantaan virus M genome segment by using a vaccinia virus recombinant.,,PMC253622,,,"A cDNA containing the complete open reading frame of the Hantaan virus (HTN) M genome segment has been cloned into vaccinia virus. This recombinant virus expresses two glycoproteins which are similar to the HTN structural glycoproteins, G1 and G2, in molecular weight, cleavage pattern, and cellular distribution. Both HTN and recombinant vaccinia virus glycoproteins are exclusively associated with the Golgi apparatus of the cell. Despite this intracellular restriction, mice inoculated with the recombinant vaccinia virus raised neutralizing antibodies against HTN. The specificity of virus neutralization appears to reside in the HTN glycoproteins, since a vaccinia virus recombinant expressing the HTN nucleocapsid protein was unable to elicit a neutralizing antibody response.",,"['Pensiero, M N', 'Jennings, G B', 'Schmaljohn, C S', 'Hay, J']",,,,
,PMC,Rotavirus diarrhoea in patient with antibody to human immunodeficiency virus (HIV),,PMC1194154,,,,,"['Mifsud, A J', 'Fagan, D']",,,,
,PMC,Demonstration of dose-response relationship in seasonal prophylaxis of respiratory infections with alpha-2b interferon.,,PMC172096,,,"Recombinant alpha-2b interferon was evaluated in two controlled trials, each lasting for 2 months or more, with different dose levels and schedules of administration. The first study was conducted during a period of transmission of type A (H1N1) and type B influenza. At 2.5 x 10(6) IU per day, no effect on influenza infection could be detected, but there appeared to be an effect on rhinovirus isolation. During the subsequent autumn 1.7 x 10(6) IU per day was found to have only a minimal effect on rhinovirus infection (efficacy from 22 to 27%). Under similar circumstances the preceding year, but with a daily dose of 3.0 x 10(6) IU, efficacy had been 76%. Since there was no evidence of change in rhinovirus strains circulating or their interferon susceptibility, this represented a dose-response relationship. It was possible to evaluate side effects in the 1,200 individuals involved. A lower dose was associated with lower frequency of symptoms of blood-tinged mucus. Persons using a placebo spray had a higher frequency of this side effect than an observed control. Using the spray 5 days a week was no less likely to produce symptoms than everyday use. Once-daily use was less likely to produce side effects than twice-daily use. There was no indication of sensitization when interferon was used for two separate periods of 4 weeks.",,"['Monto, A S', 'Albrecht, J K', 'Schwartz, S A']",,,,
,PMC,Viral agents associated with outbreaks of diarrhea in turkey flocks in Quebec.,,PMC1255400,,,"The relative importance of various enteric viruses associated with diarrhea of turkey poults was investigated by an evaluation of specimens received since 1982. Specimens originated from one to eight week old turkey poults, with mild to severe diarrhea, from 114 flocks in 42 commercial operations located in southern Quebec. The acute phase of enteritis occurred usually in poults between two and four weeks of age. Clarified intestinal contents were examined by direct electron microscopy and enzyme immunoassays. Enzyme-linked immunosorbent assays were performed with antisera to bovine rotavirus group antigen, avian reovirus types 1 to 5, and the prototype strain of the turkey enteric coronavirus. The presence of viruses could be demonstrated by electron microscopy in 55.3% of the specimens, and at least five different viruses were incriminated either alone or in combination. The coronavirus was by far the most common enteric virus with a prevalence of 47.5%. By enzyme-linked immunosorbent assay, rotavirus, reovirus and turkey coronavirus were detected in 14.5%, 18.1% and 61.4% of the specimens, respectively. By electron microscopy, 56.6% of these cases were positive for at least one virus.",,"['Dea, S', 'Tijssen, P']",,,,
,PMC,Viral and Mycoplasmal Infections of Laboratory Rodents: Effects on Biomedical Research,,PMC1680735,,,,,"Cross, Brenda",,,,
,PMC,Isolation and functional characterization of chicken intestinal intra-epithelial lymphocytes showing natural killer cell activity against tumour target cells.,,PMC1454689,,,"Intestinal intra-epithelial lymphocytes (IEL) of SC or FP chickens were isolated and examined for their natural killer (NK)-cell activity against chicken tumour cell lines, LSCC-RP9 (RP9), LSCC-RP12 (RP12), MDCC-MSB-1 (MSB-1) and MDCC-CU36 (CU36). In general, IEL of satisfactory yield and of good viability were obtained with EDTA treatment of the gut tissues, followed by rapid passages of the resultant cells through nylon-wool columns and centrifugation on two-step Percoll density gradients (45% and 80%). In 4-hr and 16-hr 51Cr-release assays, the NK-cell activity of chicken IEL depended not only upon the type of target cells but also upon the incubation time and the host genetic background. RP9, MSB-1 and CU36 were susceptible to NK lysis by IEL and by spleen cells, while RP12 was resistant to lysis even after a prolonged incubation. In kinetic studies the cytotoxicity was detactable from 2 hr after incubation and progressively increased up to 16 or 18 hr. The IEL of SC chickens revealed significantly higher levels of NK-cell activity against RP9 than FP-strain chickens, whereas their splenic NK-cell activity was not significantly different. Against MSB-1 targets, however, IEL of SC and FP chickens showed similar levels of NK-cell activity while their spleens did not (being higher in FP). When tested in FP chickens, IEL NK-cell activity was inhibited by the addition of unlabelled homologous target cells. In general, NK-cell activity was higher in the jejunum and ileum than in the duodenum and caecum. Efforts to enrich IEL NK-effector cells by discontinuous Percoll gradients were not successful. The results of the present study show that IEL of chicken intestine contain effector cells that can mediate NK-cell activity against chicken tumour cells.",,"['Chai, J Y', 'Lillehoj, H S']",,,,
,PMC,Recent respiratory and enteric adenovirus infection in children in the Manchester area.,,PMC1291420,,,"Seventy-three group B adenoviruses (29 type 3 and 44 type 7) identified in a recent community outbreak were analysed with restriction endonucleases. Considerable genetic heterogeneity was identified, particularly amongst the type 3 isolates, but this genome variation could not be correlated with either clinical or epidemiological findings. Group F adenoviruses were found in 132 (4.1%) of 3202 stool specimens from children with gastroenteritis and, after rotaviruses, they were the most common viruses identified. Unlike rotaviruses, these enteric adenoviruses were endemic throughout the 3-year study period and the greatest proportion of infections (47.6%) were found in babies under 6 months old.",,"['Richmond, S J', 'Wood, D J', 'Bailey, A S']",,,,
,PMC,Induction of alpha interferon by transmissible gastroenteritis coronavirus: role of transmembrane glycoprotein E1.,,PMC250494,,,"Epithelial cells infected with the coronavirus transmissible gastroenteritis virus (TGEV) and fixed by glutaraldehyde induced a high alpha interferon (IFN-alpha) production in nonimmune porcine as well as human or bovine peripheral blood mononuclear cells (PBMC). IFN-alpha was detected as early as 3 h after exposure of PBMC to infected cells and at producer/inducer cell ratios as low as 1/1. Two of four monoclonal antibodies directed against the viral transmembrane glycoprotein E1 could block the IFN-inducing capacity of both TGEV-infected cells and viral particles. On the other hand, IFN-alpha induction was not markedly affected by monoclonal antibodies directed against other E1 epitopes, against peplomer glycoprotein E2, or against nucleocapsid protein. Thus, these findings strongly imply that IFN induction by TGEV results from interactions between an outer membrane domain of E1 and the PBMC membrane.",,"['Charley, B', 'Laude, H']",,,,
,PMC,Antigenic site II of the rabies virus glycoprotein: structure and role in viral virulence.,,PMC250493,,,"Twelve monoclonal antibodies neutralizing the CVS strain of rabies virus were used to characterize antigenic site II of the viral glycoprotein. Nineteen antigenic mutants resistant to neutralization by some of these antibodies were selected; some continued to normally or partially bind the antibody, whereas others did not. Mutations conferring resistance to neutralization by site II-specific monoclonal antibodies were localized into two clusters, the first between amino acids 34 and 42 (seven groups of mutants) and the second at amino acids 198 and 200 (three groups of mutants). Two intermediate mutations were identified at positions 147 and 184. Four mutations resulted in reduced pathogenicity after intramuscular inoculation of the virus in adult mice. One of the mutants, M23, was 300 times and the others were 10 to 30 times less pathogenic than CVS. In three cases the attenuated phenotype was related to an important modification of antigenic site II, whereas the other known antigenic sites were unchanged.",,"['Prehaud, C', 'Coulon, P', 'LaFay, F', 'Thiers, C', 'Flamand, A']",,,,
,PMC,Distinct binding sites for zinc and double-stranded RNA in the reovirus outer capsid protein sigma 3.,,PMC363116,,,"By atomic absorption analysis, we determined that the reovirus outer capsid protein sigma 3, which binds double-stranded RNA (dsRNA), is a zinc metalloprotein. Using Northwestern blots and a novel zinc blotting technique, we localized the zinc- and dsRNA-binding activities of sigma 3 to distinct V8 protease-generated fragments. Zinc-binding activity was contained within an amino-terminal fragment that contained a transcription factor IIIA-like zinc-binding sequence, and dsRNA-binding activity was associated with a carboxy-terminal fragment. By these techniques, new zinc- and dsRNA-binding activities were also detected in reovirus core proteins. A sequence similarity was observed between the catalytic site of the picornavirus proteases and the transcription factor IIIA-like zinc-binding site within sigma 3. We suggest that the zinc- and dsRNA-binding activities of sigma 3 may be important for its proposed regulatory effects on viral and host cell transcription and translation.",,"['Schiff, L A', 'Nibert, M L', 'Co, M S', 'Brown, E G', 'Fields, B N']",,,,
,PMC,Codon usage tabulated from the GenBank Genetic Sequence Data,,PMC340914,,,,,"['Aota, Shin-ichi', 'Gojobori, Takashi', 'Ishibashi, Fumie', 'Maruyama, Takeo', 'Ikemura, Toshimichi']",,,,
,PMC,An efficient ribosomal frame-shifting signal in the polymerase-encoding region of the coronavirus IBV.,,PMC553849,,,"The polymerase-encoding region of the genomic RNA of the coronavirus infectious bronchitis virus (IBV) contains two very large, briefly overlapping open reading frames (ORF), F1 and F2, and it has been suggested on the basis of sequence analysis that expression of the downstream ORF, F2, might be mediated through ribosomal frame-shifting. To examine this possibility a cDNA fragment containing the F1/F2 overlap region was cloned within a marker gene and placed under the control of the bacteriophage SP6 promoter in a recombinant plasmid. Messenger RNA transcribed from this plasmid, when translated in cell-free systems, specified the synthesis of polypeptides whose size was entirely consistent with the products predicted by an efficient ribosomal frame-shifting event within the overlap region. The nature of the products was confirmed by their reactivity with antisera raised against defined portions of the flanking marker gene. This is the first non-retroviral example of ribosomal frame-shifting in higher eukaryotes.",,"['Brierley, I', 'Boursnell, M E', 'Binns, M M', 'Bilimoria, B', 'Blok, V C', 'Brown, T D', 'Inglis, S C']",,,,
,PMC,Sequence and translation of the murine coronavirus 5'-end genomic RNA reveals the N-terminal structure of the putative RNA polymerase.,,PMC256017,,,"A 28-kilodalton protein has been suggested to be the amino-terminal protein cleavage product of the putative coronavirus RNA polymerase (gene A) (M.R. Denison and S. Perlman, Virology 157:565-568, 1987). To elucidate the structure and mechanism of synthesis of this protein, the nucleotide sequence of the 5' 2.0 kilobases of the coronavirus mouse hepatitis virus strain JHM genome was determined. This sequence contains a single, long open reading frame and predicts a highly basic amino-terminal region. Cell-free translation of RNAs transcribed in vitro from DNAs containing gene A sequences in pT7 vectors yielded proteins initiated from the 5'-most optimal initiation codon at position 215 from the 5' end of the genome. The sequence preceding this initiation codon predicts the presence of a stable hairpin loop structure. The presence of an RNA secondary structure at the 5' end of the RNA genome is supported by the observation that gene A sequences were more efficiently translated in vitro when upstream noncoding sequences were removed. By comparing the translation products of virion genomic RNA and in vitro transcribed RNAs, we established that our clones encompassing the 5'-end mouse hepatitis virus genomic RNA encode the 28-kilodalton N-terminal cleavage product of the gene A protein. Possible cleavage sites for this protein are proposed.",,"['Soe, L H', 'Shieh, C K', 'Baker, S C', 'Chang, M F', 'Lai, M M']",,,,
,PMC,Initiation and termination of duck hepatitis B virus DNA synthesis during virus maturation.,,PMC256000,,,"We characterized a number of important features of the structure of the cohesive overlap region of the DNA genome of duck hepatitis B virus. The 5'-terminal nucleotide of minus-strand DNA was localized to nucleotide 2537, a G residue within the 12-base repeat sequence DR1. This G residue was shown to be the site of a covalent linkage to a protein, consistent with speculation that this protein is the primer of minus-strand synthesis, which occurs by reverse transcription. The 3' terminus of the minus strand was heterogeneous, being mapped to nucleotides 2530 and 2531, indicating that the minus strand is terminally redundant by seven or eight bases and ends at the putative 5' end of the transcribed RNA template (pregenome) for reverse transcription. We previously demonstrated that the presumptive RNA primer of plus-strand synthesis remains attached to plus-strand DNA during virus maturation; moreover, the sequence of this primer suggested an origin from the 5' end of the pregenome (J.-M. Lien, C. E. Aldrich, and W. S. Mason, J. Virol. 57:229-236, 1986). We show here that over 75% of plus-strand primers are capped, further supporting the idea that these primers are uniquely derived from the 5' end of the pregenome. Finally, we found that seemingly mature duck hepatitis B virus genomes are incomplete by at least 12 bases, in that the 12-base repeat sequence DR2 is not copied into plus-strand DNA during virus maturation. Since DR2 in virion DNA is duplexed with the RNA primer of plus-strand synthesis, it is possible that the failure to make complete plus strands is due to an inability of the viral DNA polymerase to carry out a displacement of the bound RNA primer.",,"['Lien, J M', 'Petcu, D J', 'Aldrich, C E', 'Mason, W S']",,,,
,PMC,In vivo and in vitro models of demyelinating disease: activation of the adenylate cyclase system influences JHM virus expression in explanted rat oligodendrocytes.,,PMC255995,,,"The specificity of JHM virus (JHMV) tropism for rat oligodendrocytes, as one of the primary host cells in the central nervous system, is maintained after explanation (S. Beushausen and S. Dales, Virology 141:89-101, 1985). The temporal correlation between onset of resistance to JHMV infection in vivo, completion of myelination, and maturation of the central nervous system can be simulated in vitro by inducers of oligodendrocyte differentiation (Beushausen and Dales, Virology, 1985). Stimulation of differentiation through the elevation of intracellular cyclic AMP (cAMP) levels suggests a possible connection between activation of the adenylate cyclase system and coronavirus expression. Chromatographic analysis of cAMP-dependent protein kinase activity in cytosol extracts prepared from astrocytes or oligodendrocytes revealed that both glial cell types were deficient in protein kinase I, indicating that expression of coronavirus in differentiated cells was not contingent upon the presence of protein kinase I. However, treatment with N6,2'-O-dibutyryladenosine-3',5'-cyclic monophosphate (dbcAMP) resulted in a severalfold enhancement of the free regulatory subunit (RI) in oligodendrocytes but not in astrocytes. The RII subunit in both neural cell types was relatively unaffected. Rapid increase in RI due to dbcAMP treatment was correlated with inhibition of JHMV expression. Other differentiation inducers, including 8-Br cAMP and forskolin which, by contrast, caused a decrease in detectable RI, also blocked JHMV expression. This apparent anomaly can be attributed to an increased turnover of RI due to destabilization of the molecule which occurs upon site-specific binding of the cyclic nucleotides. On the basis of these observations, we conclude that the state of oligodendrocyte differentiation manifested with the modulation of RI regulates JHMV expression. The differentiation process did not affect either virus adsorption or sequestration but appeared to inhibit the expression of viral RNA and proteins, implying that replication was inhibited at some step between penetration and initiation of genomic functions, perhaps at the stage of uncoating. We therefore examined the possibility that protein kinases and phosphatases, which influence cellular regulation during cAMP-induced differentiation, may be responsible for the phenomenon of coronavirus suppression in oligodendrocytes. Evidence was obtained indicating that normal processing of the phosphorylated nucleocapsid protein is inhibited in differentiated oligodendrocytes, consistent with the notion that JHMV replication might be arrested during uncoating.",,"['Beushausen, S', 'Narindrasorasak, S', 'Sanwal, B D', 'Dales, S']",,,,
,PMC,Pathogenesis of bronchiolitis and pneumonia induced in neonatal and weanling rats by parainfluenza (Sendai) virus.,,PMC1899730,,,"The objective of this research was to identify potential mechanisms that might account for the greater susceptibility of neonatal rats (5 days old) as compared with weanling rats (25 days old) to viral-induced lung injury. Sites of viral replication, the sequential development of bronchiolitis and pneumonia, and systemic humoral immune responses were compared between neonatal and weanling rats from 2 to 17 days after being inoculated intranasally with parainfluenza Type 1 (Sendai) virus. In both neonatal and weanling rats, viral antigen was demonstrated by immunoperoxidase technique and viral nucleocapsids, and budding virions were demonstrated by transmission electron microscopy in bronchiolar ciliated and nonciliated epithelial cells as early as 2 days after inoculation. Similar evidence of viral replication was also demonstrated in both ages of rats in alveolar Type I and Type II epithelial cells and in macrophages. Neither virus nor viral antigens was identified in endothelial cells or interstitial cells of interalveolar septa. Bronchiolitis was induced as early as 2 days after inoculation in both ages of rats and was characterized by necrosis, erosion, and hyperplasia of epithelial cells. Multifocal to locally extensive interstitial pneumonia centered on bronchioles, was characterized by alveolar epithelial cell damage and by infiltration of neutrophils, macrophages, and lymphocytes in alveolar septa and spaces and was observed as early as 2 days after inoculation in both age groups of rats. Interstitial pneumonia of maximal severity occurred in weanling rats at 5 days after inoculation, whereas maximal pneumonia of comparable severity occurred in neonatal rats at 8 days after inoculation. Epithelial repair and resolution of bronchiolitis and pneumonia were largely complete in both ages of rats by 17 days after inoculation. Virus was recovered from lung homogenates of neonatal and weanling rats as early as 2 days after inoculation. In weanling rats, infective virus could not be recovered from lung beyond 6 days after inoculation, whereas in neonatal rats virus could be recovered from lung as late as 10 days after inoculation. Viral persistence in neonatal rats was associated with a delayed onset of serum antibody to the virus, compared with weanling rats. The results indicate that the cellular sites of viral replication and the pattern of inflammatory reactions are closely comparable between neonatal and weanling rats inoculated with Sendai virus.(ABSTRACT TRUNCATED AT 400 WORDS)",,"['Castleman, W. L.', 'Brundage-Anguish, L. J.', 'Kreitzer, L.', 'Neuenschwander, S. B.']",,,,
,PMC,Protection of newborn calves against fatal multisystemic infectious bovine rhinotracheitis by feeding colostrum from vaccinated cows.,,PMC1255364,,,"To determine whether consumption of colostrum with high levels of serum neutralizing antibody to bovine herpesvirus 1 would protect neonatal calves from the frequently fatal multisystemic form of infectious bovine rhinotracheitis, Holstein calves were fed for 48 h after birth with either pooled colostrum from seropositive vaccinated cows or colostrum from seronegative unvaccinated cows. The serum neutralizing antibody achieved in the former calves was between 64 and 256 and the titer in the latter calves was below 8. At 48 h of age the calves were challenged by aerosolization with bovine herpesvirus 1. All five seronegative calves died or were euthanized in a moribund state between days 5 and 7 of the trial, whereas all five seropositive animals remained healthy throughout the study. Twice daily clinical examination revealed significantly lower scores in the seronegative group from 60 h postinfection. Relative lung weights were greater in the seronegative group, associated with a severe acute necrotizing bronchiolitis with fibrin exudation. The seronegative group of calves also demonstrated an acute necrotizing rumenitis, pharyngitis, glossitis, esophagitis, laryngitis and tracheitis. The seropositive animals had only small areas of subacute necrotizing fibrinopurulent rhinitis. Bovine herpesvirus 1 virus was isolated from all nasal passages of all calves but isolation of virus in the seronegative calves was made from the trachea (5/5), lung (4/5), bronchial lymph nodes (4/5), spleen (4/5), thymus (3/5), liver (2/5), rumen (2/5) and brain (1/5).(ABSTRACT TRUNCATED AT 250 WORDS)",,"['Mechor, G D', 'Rousseaux, C G', 'Radostits, O M', 'Babiuk, L A', 'Petrie, L']",,,,
,PMC,Amprolium and Furazolidone as Preventive Treatment for Intestinal Coccidiosis of Piglets,,PMC1680524,,,"Two coccidiostats, amprolium and furazolidone, were used as preventive treatments for intestinal coccidiosis in three-day-old piglets experimentally infected with 50,000 sporulated oocysts of Isospora suis. All infected piglets, treated or not, displayed clinical signs compatible with coccidiosis. Diarrhea and anorexia appeared around five days postinoculation in the non-treated and in the amprolium-treated groups; these signs were delayed to days 7 and 8 postinoculation in the furazolidone-treated group. The treatments did not prevent growth retardation. Amprolium seemed to reduce oocyst shedding whereas furazolidone had no effect. Villous atrophy was present in all infected piglets.",,"['Girard, Christiane', 'Morin, Michel']",,,,
,PMC,The Pathogenesis of Multiple Sclerosis: The Bradshaw Lecture 1986,,PMC5379368,,,,,"McDonald, W. I.",,,,
,PMC,Tumor necrosis factor amplifies measles virus-mediated Ia induction on astrocytes.,,PMC299267,,,"We describe the induction of Ia on cultured astrocytes by measles virus and the amplification of this induction by tumor necrosis factor (TNF). Measles virus induces Ia on rat astrocytes by direct interaction with these cells. TNF does not induce significant levels of Ia at any dose from 1 to 10,000 units/ml. As little as 10 units of TNF per ml, however, amplifies Ia-inducing signals generated by measles virus in astrocytes. In contrast, TNF and measles virus induce class I major histocompatibility complex (MHC) antigens, when applied individually, and TNF amplification of measles virus class I MHC induction is not apparent. The induction of either Ia or class I MHC antigens on rat astrocytes by measles virus does not depend on glial-derived soluble factors generated during infection. Since brain cells are normally lacking MHC antigens upon which T cells depend for interaction with antigen presenting cells, these data indicate that the ability of measles virus to directly stimulate MHC antigen expression and the ability of TNF to amplify Ia expression locally in the brain may be important in initiating cell-mediated immune response to viral infection.",,"['Massa, P T', 'Schimpl, A', 'Wecker, E', 'ter Meulen, V']",,,,
,PMC,The influenza hemagglutinin precursor as an acid-sensitive probe of the biosynthetic pathway.,,PMC553685,,,"The hemagglutinin of influenza virus (HA), an acid-activated membrane fusion protein, is synthesized in the endoplasmic reticulum and transported through the Golgi complex to the cell surface of infected cells as an uncleaved, fusion-incompetent precursor, HA0. The mature, proteolytically activated HA is known to undergo a rapid, irreversible, acid-induced conformational change which mediates membrane fusion and virus penetration. On the basis of antigenic modifications and the acquisition of trypsin susceptibility, we demonstrate here that HA0, while unable to cause fusion, is acid sensitive. It undergoes irreversible conformational changes quite similar to those of HA at mildly acidic pH (pH less than 6.0). The ectodomain of HA0 does not, however, acquire hydrophobic properties and the changes occur in a less concerted manner (the pH dependence is much broader and the rate of conversion slower). These differences are likely to account for the inability of acid-treated HA0 to trigger membrane fusion. It was shown, moreover, that HA0 acquired its acid-sensitive properties immediately following trimerization in the endoplasmic reticulum. Since HA0 did not convert to the acid form at any point during its intracellular transport, we concluded that the trans-Golgi compartment, known to be more acidic than the cytosol and involved in constitutive membrane transport, is not likely to have a pH less than 6.0.",,"['Boulay, F', 'Doms, R W', 'Wilson, I', 'Helenius, A']",,,,
,PMC,"16, 16 Dimethyl prostaglandin E2 prevents the development of fulminant hepatitis and blocks the induction of monocyte/macrophage procoagulant activity after murine hepatitis virus strain 3 infection.",,PMC442316,,,"16, 16 Dimethyl prostaglandin E2 (dmPGE2), a known cytoprotective agent, was examined for its ability to alter the course of fulminant hepatitis in an experimental model of fulminant viral hepatitis, murine hepatitis murine hepatitis type 3 (MHV-3). Fully susceptible BALB/cJ mice, infected with 100 50% lethal doses (LD50) of MHV-3 developed histologic and biochemical evidence of fulminant hepatitis, as evidenced by massive hepatic necrosis with hypoglycemia, metabolic acidosis, and a markedly elevated serum alanine aminotransferase (ALT) (mean, 1,402 +/- 619 IU/liter). In contrast, animals treated with dmPGE2 either before or after infection (up to 48 h) demonstrated a marked reduction in both histologic and biochemical evidence of liver damage as characterized by normal blood glucose, total CO2, and ALT determinations (mean ALT, 63 +/- 40 IU/liter). Treatment of infected mice with PGF2 alpha demonstrated no cytoprotective effects. High titers of infectious virus were recovered from the livers of both dmPGE2-treated and -untreated animals throughout the course of infection. In a parallel in vitro study, dmPGE2 (10(-4)-10(-8) M) demonstrated a similar cytoprotective effect on monolayers of isolated cultured hepatocytes from fully susceptible BALB/cJ mice infected at a multiplicity of infection of 0.1, 1.0, and 10.0. In addition, splenic macrophages recovered from infected and untreated BALB/cJ mice demonstrated a marked augmentation in procoagulant activity (PCA) from a basal 10 +/- 5 mU/10(6) splenic macrophages to a maximum of 615 +/- 102 mU/10(6) splenic macrophages, whereas no increase in macrophage PCA was detected in infected animals treated with dmPGE2. These results suggest that dmPGE2, without detectably altering viral replication or infectivity in vivo, confers a marked cytoprotective effect on hepatocytes both in vivo and in vitro, and prevents the induction of macrophage PCA in vivo in fully susceptible BALB/cJ mice after murine hepatitis virus type 3 infection.",,"['Abecassis, M', 'Falk, J A', 'Makowka, L', 'Dindzans, V J', 'Falk, R E', 'Levy, G A']",,,,
,PMC,Diagnosis of porcine and bovine enteric coronavirus infections using cloned cDNA probes.,,PMC269289,,,"Molecular clones representing the first 2,000 bases from the 3' end of the porcine transmissible gastroenteritis coronavirus genome and the first 2,160 bases from the 3' end of the bovine enteric coronavirus genome were used in dot blot hybridization assays to detect viral RNA from cell culture and from fecal specimens. In each case, the cloned DNA represents approximately 10% of the genome. The cloned sequence for each virus encompasses the 3' noncoding region, the nucleocapsid protein gene, and a large portion of the matrix protein gene. 32P-labeled cDNA probes prepared from these clones detected as little as 25 pg of RNA from the parental virus but did not detect RNA from the nonparental virus even when amounts of up to 10 ng per dot were used. This specificity reflects the antigenic diversity between these two coronaviruses. The hybridization assay could also detect coronaviruses antigenically closely related to the parental virus but not coronaviruses belonging to an antigenically unrelated subgroup. Dot blot hybridization for transmissible gastroenteritis coronavirus diagnosis was compared with the routine procedures of virus isolation and electron microscopy as a diagnostic test.",,"['Shockley, L J', 'Kapke, P A', 'Lapps, W', 'Brian, D A', 'Potgieter, L N', 'Woods, R']",,,,
,PMC,RNA recombination of coronaviruses: localization of neutralizing epitopes and neuropathogenic determinants on the carboxyl terminus of peplomers.,,PMC299120,,,"Murine coronaviruses undergo RNA recombination at a very high frequency. We have obtained a series of recombinant viruses using neutralizing monoclonal antibodies in conjunction with temperature-sensitive markers. All of the recombinants obtained have a crossover within gene C, which encodes the peplomer protein of the virus. The genetic structure of these recombinants suggests that the antigenic regions recognized by these neutralizing monoclonal antibodies are localized on the carboxyl-terminal one-third of the peplomer protein. Since the two monoclonal antibodies used are also associated with the critical determinants of virus neuropathogenicity, we conclude that both the neutralizing antibody binding sites and determinants of pathogenicity are localized at the carboxyl-terminal one-third of the peplomer. The variation of crossover sites in different recombinant viruses also allowed precise mapping of additional antigenic sites. RNA recombination thus presents a powerful genetic tool, and the carboxyl-terminal localization of the biological functions of peplomers suggests a distinct conformation of these viral membrane proteins.",,"['Makino, S', 'Fleming, J O', 'Keck, J G', 'Stohlman, S A', 'Lai, M M']",,,,
,PMC,Epitope-specific antibody responses to virulent and avirulent feline infectious peritonitis virus isolates.,,PMC269263,,,"Feline infectious peritonitis virus (FIPV) has been isolated several times from infected cats. Some of these isolates vary markedly in their ability to cause disease. Specific-pathogen-free cats were inoculated with the avirulent FIPV-UCD-2 isolate or the extremely virulent FIPV-79-1146 isolate or both. After 1 month, cats which had received FIPV-79-1146 were either dead or showed clinical signs of FIP. All cats which received only FIPV-UCD-2 remained healthy up to 6 months after inoculation. Antibody-mediated immune enhancement of disease was not observed in cats which received FIPV-UCD-2 before inoculation with FIPV-79-1146. Monoclonal antibodies which recognized type-specific epitopes on each of the structural polypeptides of these two viruses were used in competitive-inhibition enzyme-linked immunosorbent assays to analyze the humoral immune responses of the cats. All cats produced antibodies to epitopes found on the homologous virus. In addition, cats inoculated with FIPV-79-1146 also produced antibodies which inhibited the binding of the anti-FIPV-UCD-2 E1 monoclonal antibody. One cat inoculated twice with FIPV-UCD-2 produced antibodies which inhibited the binding of the anti-FIPV-79-1146 N- and E1-specific monoclonal antibodies. Competitive enzyme-linked immunosorbent assays may prove useful in distinguishing cats which are infected with virulent FIPV isolates from cats infected with avirulent feline coronaviruses.",,"['Fiscus, S A', 'Rivoire, B L', 'Teramoto, Y A']",,,,
,PMC,Functional differences in the peplomer glycoproteins of feline coronavirus isolates.,,PMC255718,,,"The feline coronaviruses can be divided into two distinct antigenic groups on the basis of antigenic differences found on the peplomer (E2) glycoprotein of the virus. Because the E2 glycoprotein is responsible for many of the biological functions of coronaviruses, experiments were done to determine whether there were any E2 functional differences between these two antigenic groups. The avirulent feline infectious peritonitis virus (FIPV) isolate FIPV-UCD-2, which has one antigenic type of E2, was less rapidly internalized and could not spread from cell to cell in the presence of neutralizing antibody. Two virulent isolates, FIPV-DF2 and FIPV-79-1146, as well as the non-FIP-causing feline enteric coronavirus (FECV) isolate FECV-79-1683, all of which have the second antigenic type of E2, were very rapidly internalized and were able to spread from cell to cell despite the presence of neutralizing antibody. The avirulent FIPV-UCD-2 and FECV-79-1683 isolates were more labile at 37 degrees C at pHs of 6.5 and above than were the virulent FIPV-DF2 and FIPV-79-1146 isolates.",,"['Fiscus, S A', 'Teramoto, Y A']",,,,
,PMC,Antigenic comparison of feline coronavirus isolates: evidence for markedly different peplomer glycoproteins.,,PMC255709,,,"The antigenic relationships among seven feline coronavirus isolates were investigated by using a panel of 26 monoclonal antibodies (MAbs). The MAbs were categorized into five immunoreactive groups which were used to delineate two antigenic types of feline coronaviruses. One antigenic type included the more virulent feline infectious peritonitis virus (FIPV) isolates (FIPV-UCD-1, FIPV-UCD-4, FIPV-TN406, FIPV-DF2, and FIPV-79-1146), whereas the second antigenic type was composed of the avirulent isolate FIPV-UCD-2. The feline enteric coronavirus isolate FECV-79-1683 shared some characteristics of both of the major antigenic groups. Epitopes on the nucleocapsid and envelope polypeptides were in general highly conserved among both antigenic types, although a few type-specific antigenic sites were discriminated. The most striking finding was the marked antigenic difference in the peplomer (E2) glycoproteins between the two antigenic types. Seven anti-E2 MAbs reacted with one antigenic type of E2, whereas seven other anti-E2 MAbs recognized a different antigenic form of E2. None of the 14 anti-E2 MAbs reacted with all of the isolates.",,"['Fiscus, S A', 'Teramoto, Y A']",,,,
,PMC,"Inhibition of murine hepatitis virus infections by the immunomodulator 2,3,5,6,7,8-hexahydro-2-phenyl-8,8-dimethoxy-imidazo[1,2a]pyridine (PR-879-317A).",,PMC174883,,,"PR-879-317A (2,3,5,6,7,8-hexahydro-2-phenyl-8,8-dimethoxy-imidazo [1,2a]pyridine) has been found to be a T-cell-selective immunomodulating agent. In the current studies, a series of experiments was designed to determine the potential antiviral activity of this compound in mice infected with murine hepatitis virus. In a comparative antiviral experiment, the activity seen was superior to that of levamisole, a known immunorestorative agent. This activity was characterized by an increase in the 21-day survival frequency, a decrease in hepatic discoloration, a decrease in the amount of infectious virus recoverable from the liver, and normalization of serum glutamic oxalacetate and pyruvate transaminase levels. A comparison of treatment routes indicated the relative efficacies as intraperitoneal greater than per os greater than intramuscular greater than or equal to subcutaneous. Alteration of the treatment schedule markedly affected the antiviral effect; prophylactic or therapeutic treatments once or twice daily for 3 days were usually effective. Single treatments begun 4 h before or 24 h after virus inoculation were highly efficacious. Three treatments administered on alternate days, beginning 48 h before virus inoculation, proved moderately effective. Thrice-daily treatments were ineffective, as were treatments with durations of greater than 3 days. The optimal dosage varied according to the treatment route and dosage schedule. When assessed for direct antiviral activity in vitro, PR-879-317A failed to demonstrate any significant activity against murine hepatitis virus. The positive in vivo activity noted might therefore be the result of immune modulation rather than a direct antiviral effect.",,"['Sidwell, R W', 'Huffman, J H', 'Call, E W', 'Warren, R P', 'Radov, L A', 'Murray, R J']",,,,
,PMC,Susceptibility of Aedes albopictus C6/36 cells to viral infection.,,PMC269180,,,"The susceptibility of the C6/36 clone of Aedes albopictus monolayer cell cultures was determined with 46 prototype viruses passed through three subcultures. Viral growth was confirmed by titration of the passage material in other susceptible host systems. Nineteen viruses demonstrated good growth in C6/36 cells: coxsackievirus group A type 10 and group B types 2, 3, 4, and 5; enterovirus 69; mumps virus; poliovirus types 1 to 3; reovirus types 1 to 3; vaccinia virus; dengue virus type 2; eastern equine encephalomyelitis virus; La Crosse virus; Rocio virus; and St. Louis encephalitis virus. Ten viruses did not adapt to growth in the C6/36 cultures. Seventeen other virus strains displayed only limited growth which was primarily restricted to the initial C6/36 passage or was detected by hemagglutinin reactions without observable cell degeneration. Of the 46 viruses, 33 (72%) were capable of initiating infection with a demonstrable cytopathic effect in the initial C6/36 passage. Hemagglutination or complement fixation titers or both were obtained with dengue virus type 2, eastern equine encephalomyelitis virus, La Crosse virus, mumps virus, reovirus types 1 to 3, and Rocio, St. Louis encephalitis, and vaccinia viruses.",,"White, L A",,,,
,PMC,Some Advances in the Diagnosis of Respiratory Virus Infections,,PMC5379341,,,,,"Tyrrell, D. A. J.",,,,
,PMC,Experimental studies of immunologically mediated enteropathy. II. Role of natural killer cells in the intestinal phase of murine graft-versus-host reaction.,,PMC1453377,,,"This study has investigated whether natural killer (NK) cells play a protective or an effector role in unirradiated mice with graft-versus-host reaction (GvHR). Treatment of (CBA X BALB/c)F1 mice with anti-asialo GM1 (ASGM1) antibody produced a profound depletion of resting NK-cell activity and also inhibited the normal enhancement of NK activity found after induction of a GvHR with CBA spleen cells. Compared with normal hosts, mice treated with anti-AsGM1 developed less splenomegaly in GvHR and did not show the crypt hyperplasia normally found in this model of GvHR. Anti-AsGM1 also produced a small but significant reduction of intraepithelial lymphocyte (IEL) numbers in the jejunum of control mice. We conclude that intestinal NK cells are an essential component of the local delayed-type hypersensitivity (DTH) reaction which is responsible for the intestinal phase of GvHR in unirradiated mice.",,"['Mowat, A M', 'Felstein, M V']",,,,
,PMC,Protection between different serotypes of bovine rotavirus in gnotobiotic calves: specificity of serum antibody and coproantibody responses.,,PMC269135,,,"In a previous study, different U.S. isolates of bovine rotavirus were studied for their serotypes and cross-protective properties (G. N. Woode, N. E. Kelso, T. F. Simpson, S. K. Gaul, L. E. Evans, and L. Babiuk, J. Clin. Microbiol. 18:358-364, 1983). Three viruses belonging to two different serotype groups were used as vaccines in gnotobiotic calves, which were subsequently challenged with B641 or B223, representing the two bovine serotypes. In the present work, the experiments were repeated with more calves and the specificity of their antibody responses was measured and compared with the results of the protection studies. Protection between different serotypes occurred under both homologous and heterologous conditions but was not directly serotype dependent. B223 virus showed both homologous and heterologous protection against B223 and B641 challenge viruses. This was a one-way reaction, as B641 did not induce protection against B223. Neonatal calf diarrhea virus vaccine produced neither homologous (against B641) nor heterologous (against B223) protection. The plaque reduction neutralization titers of serum antibody and coproantibody did not predict a state of protection against the challenge virus. Calves vaccinated with neonatal calf diarrhea virus or B641 developed neutralizing antibodies to their respective heterologous challenge viruses but were not protected. After challenge, the boosted coproantibody plaque reduction neutralization response to the original vaccine virus was greater than that to the challenge virus.",,"['Woode, G N', 'Zheng, S L', 'Rosen, B I', 'Knight, N', 'Gourley, N E', 'Ramig, R F']",,,,
,PMC,Coronavirus E1 glycoprotein expressed from cloned cDNA localizes in the Golgi region.,,PMC254216,,,"Cloned cDNA encoding the membrane glycoprotein E1 of the coronavirus mouse hepatitis virus strain A59 was expressed transiently in a monkey fibroblast cell line (COS) by using a simian virus 40-based vector. As determined by indirect immunofluorescence microscopy, the E1 protein accumulated intracellularly in a perinuclear region coincident with a Golgi marker. The same three species of E1 that occur in virus-infected cells were also found in transfected cells. These are one unglycosylated form and two apparently O-glycosylated forms that could be labeled in a tunicamycin-resistant fashion with [3H]glucosamine. Because O glycosylation occurs posttranslationally in the Golgi apparatus, we could show, by monitoring the rate of acquisition of oligosaccharides, that the transport of E1 from the rough endoplasmic reticulum to the Golgi apparatus had a half time of between 15 and 30 min.",,"['Rottier, P J', 'Rose, J K']",,,,
,PMC,In vitro replication of mouse hepatitis virus strain A59.,,PMC254184,,,"An in vitro replication system for mouse hepatitis virus (MHV) strain A59 was developed using lysolecithin to produce cell extracts. In extracts of MHV-infected cells, radiolabeled UMP was incorporated at a linear rate for up to 1 h into RNA, which hybridized to MHV-specific cDNA probes and migrated in denaturing formaldehyde-agarose gels to the same position as MHV genomic RNA. The incorporation of [32P]UMP into genome-sized RNA in vitro correlated with the observed increase of [3H]uridine incorporation in MHV-infected cells labeled in vivo. Incorporation of [32P]UMP into genome-sized RNA was inhibited when extracts were incubated with puromycin. The addition to the assay of antiserum to the MHV-A59 nucleocapsid protein N inhibited synthesis of genome-sized RNA by 90% compared with the addition of preimmune serum. In contrast, antiserum to the E1 or E2 glycoproteins did not significantly inhibit RNA replication. In vitro-synthesized RNA banded in cesium chloride gradients as a ribonucleoprotein complex with the characteristic density of MHV nucleocapsids isolated from virions. These experiments suggest that ongoing protein synthesis is necessary for replication of MHV genomic RNA and indicate that the N protein plays an important role in MHV replication.",,"['Compton, S R', 'Rogers, D B', 'Holmes, K V', 'Fertsch, D', 'Remenick, J', 'McGowan, J J']",,,,
,PMC,Intratypic recombination of polioviruses: evidence for multiple crossing-over sites on the viral genome.,,PMC254164,,,"Intratypic recombinant polioviruses were isolated from cells that were coinfected with two temperature-sensitive (ts) mutants of poliovirus type 1, ts035Gr and ts247. After phenotypic characterization of these recombinants, their proteins were studied by polyacrylamide gel electrophoresis, and their genomes were analyzed by RNase T1 fingerprinting and partial nucleotide sequencing. Segregation of specific phenotypic and biochemical characteristics inherited from the parental viruses demonstrated that crossing-over could occur in at least four distinct regions of the genome. Possible mechanisms for recombination are discussed.",,"['Agut, H', 'Kean, K M', 'Bellocq, C', 'Fichot, O', 'Girard, M']",,,,
,PMC,Comparative properties of feline coronaviruses in vitro.,,PMC1255305,,,"Two feline coronaviruses were characterized to determine their biological properties in vitro and their antigenic relatedness to a previously recognized feline infectious peritonitis virus and canine coronavirus. The viruses, designated WSU 79-1146 and WSU 79-1683, were shown to have comparable growth curves with the prototype feline infectious peritonitis virus. Treatment of the feline infectious peritonitis virus strains with 0.25% trypsin indicated that they were relatively resistant to proteolytic inactivation when compared with the feline enteric coronavirus strain. This observation may serve as a useful in vitro marker to distinguish closely related members of the feline coronavirus group. Plaque assay results indicated that the feline infectious peritonitis virus strains produced large homogeneous plaques in comparison to the feline enteric coronavirus strain and canine coronavirus, which showed a heterogenous plaque size distribution. No naturally temperature sensitive mutants were detected in either of the feline coronavirus populations. Both of the viruses were antigenically related to feline infectious peritonitis virus and to a lesser extent to canine coronavirus by virus neutralization.",,"['McKeirnan, A J', 'Evermann, J F', 'Davis, E V', 'Ott, R L']",,,,
,PMC,Catabolism of homologous murine monoclonal hybridoma IgG antibodies in mice.,,PMC1453269,,,"Two neutralizing monoclonal hybridoma antibodies to the surface spike glycoprotein E2 of the JHM strain of murine hepatitis virus were injected into homologous BALB/c mice, and their biological half-lives were determined by sequential titration of plasma samples in a virus-specific enzyme immunoassay. Intravascular half-lives of monomeric immunoglobulins were estimated at 8.0 +/- 1.5 days for antibody 5B19.3, an IgG1, and 12.7 +/- 2.4 days for antibody 4B11.6, an IgG2a. These catabolic rates are statistically different from each other (P less than 0.001) and significantly higher than previously reported values, which were all obtained with radiolabelled polyclonal or myeloma immunoglobulins of unknown specificities. Failure to remove aggregated 4B11.6 antibodies by high-speed centrifugation yielded a statistically significant acceleration of biological turnover (half-life 9.9 +/- 1.6 days; P less than 0.01).",,"['Talbot, P J', 'Buchmeier, M J']",,,,
,PMC,"Thymus-dependent and -independent regulation of Ia antigen expression in situ by cells in the synovium of rats with streptococcal cell wall-induced arthritis. Differences in site and intensity of expression in euthymic, athymic, and cyclosporin A-treated LEW and F344 rats.",,PMC424298,,,"Euthymic LEW rats, when injected with streptococcal cell walls, exhibited rapid onset development of acute exudative arthritis coincident with enhanced synovial expression of Ia antigen. By 21 d after injection, the expression of Ia was markedly increased compared with basal conditions and paralleled the severity of the later developing proliferative and erosive disease. Immunodeficient athymic and cyclosporin A-treated LEW rats developed only the early phase arthritis, which was again paralleled by synovial Ia expression. Chronic expression of high levels of Ia antigen was not observed. Histocompatible F344 rats, both athymic and euthymic, developed minimal, if any, clinically significant arthritis and did not exhibit the enhanced Ia expression demonstrated in the LEW rats. Our results indicate that enhanced synovial Ia expression parallels clinical disease severity and varies by rat strain, and that the rapid onset enhanced synovial Ia expression is thymus independent, whereas the markedly enhanced chronic phase Ia expression is thymus dependent.",,"['Wilder, R L', 'Allen, J B', 'Hansen, C']",,,,
,PMC,Detection of Breda virus antigen and antibody in humans and animals by enzyme immunoassay.,,PMC266050,,,"Enzyme immunoassays were developed for the detection of Breda virus antibody and antigen. Cattle sera collected in the United Kingdom were found to have a high prevalence of antibody (55%) to Breda virus when examined in a competitive enzyme-linked immunosorbent assay. A low prevalence of antibody was found in pigs (2.2%), and no antibody was found in sheep or goat sera. No antibody to either Breda virus or Berne virus was detected in human sera collected from veterinarians and farm workers. Only 1 of 430 human fecal specimens (0.2%) contained Breda virus antigen detectable by enzyme-linked immunosorbent assay.",,"['Brown, D W', 'Beards, G M', 'Flewett, T H']",,,,
,PMC,Site-specific antibodies define a cleavage site conserved among arenavirus GP-C glycoproteins.,,PMC254053,,,"Arenaviruses share a common strategy for glycoprotein synthesis and processing in which a mannose-rich precursor glycoprotein, termed GP-C in lymphocytic choriomeningitis virus (LCMV), is posttranslationally processed by oligosaccharide trimming and proteolytic cleavage to yield two structural glycoproteins, GP-1 and GP-2. Mapping the orientation and proteolytic cleavage site(s) in such polyproteins has traditionally required direct protein sequencing of one or more of the cleaved products. This technique requires rigorous purification of the products for sequencing and may be complicated by amino-terminal modifications which interfere with sequence analysis. We used an alternative approach in which synthetic peptides corresponding to sequences bracketing a potential protease cleavage site were used to raise antisera which define the boundaries of the cleaved products. We found that cleavage of LCMV GP-C to yield GP-1 and GP-2 occurs within a 9-amino-acid stretch of GP-C which contains a paired basic amino acid group -Arg-Arg-, corresponding to amino acids 262 to 263 in the LCMV GP-C sequence. By comparison with the predicted amino acid sequences of a second LCMV strain, LCMV-WE, as well as with the deduced amino acid sequences of the New World arenavirus Pichinde and the Old World virus Lassa, we observed similar conservation of paired basic and flanking amino acid sequences among these viruses.",,"['Buchmeier, M J', 'Southern, P J', 'Parekh, B S', 'Wooddell, M K', 'Oldstone, M B']",,,,
,PMC,Seroepidemiological studies on the occurrence of common respiratory infections in paediatric student nurses and medical technology students.,,PMC2235283,,,"The occupational risk of acquiring minor respiratory infections for paediatric student nurses was estimated by performing serological examinations with influenza A, B, C, parainfluenza, mumps, respiratory syncytial virus, adenovirus and Mycoplasma pneumoniae at 6-month intervals over a period of 4 years in paediatric student nurses at two schools of nursing and students at one school of medical technology. Titre increases against all tested agents occurred 1.86 times more often in the student nurses than in the medical technology students, the most frequent agents in both groups being influenza A and B. No difference in the relative distribution of the agents could be verified in the two occupational groups. Data on the protective value of pre-infectious antibody levels for influenza A, B, and coronavirus OC43 and on the importance of the spread of single agents among classmates are presented.",,"['Gerth, H. J.', 'Grüner, C.', 'Müller, R.', 'Dietz, K.']",,,,
,PMC,Monoclonal antibody passive hemagglutination and capture enzyme-linked immunosorbent assays for direct detection and quantitation of F41 and K99 fimbrial antigens in enterotoxigenic Escherichia coli.,,PMC265883,,,"Production of diarrhea in neonatal calves by enterotoxigenic Escherichia coli depends on its ability to attach to the epithelial cells of the intestine via surface adhesins called pili or fimbriae and to secrete enterotoxins. The most important of these fimbriae are designated K99 and F41. We produced and characterized a murine monoclonal antibody specific to F41. This monoclonal antibody and a K99-specific monoclonal antibody were used to develop sensitive and specific passive hemagglutination and capture enzyme-linked immunosorbent assays (ELISAs) for detection and quantitation of F41 and K99 antigens in E. coli cultures and culture supernatants. The capture ELISA systems exhibited excellent sensitivity and specificity, whereas the passive hemagglutination systems appeared to be oversensitive. The ability of the capture ELISAs to detect K99 and F41 fimbrial antigens in fecal specimens from calves was evaluated. Fimbrial antigens were detected in six of six specimens from scouring calves but not in four of four specimens from nonscouring calves.",,"['Raybould, T J', 'Crouch, C F', 'Acres, S D']",,,,
,PMC,Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides.,,PMC174645,,,"Lipids in fresh human milk do not inactivate viruses but become antiviral after storage of the milk for a few days at 4 or 23 degrees C. The appearance of antiviral activity depends on active milk lipases and correlates with the release of free fatty acids in the milk. A number of fatty acids which are normal components of milk lipids were tested against enveloped viruses, i.e., vesicular stomatitis virus, herpes simplex virus, and visna virus, and against a nonenveloped virus, poliovirus. Short-chain and long-chain saturated fatty acids had no or a very small antiviral effect at the highest concentrations tested. Medium-chain saturated and long-chain unsaturated fatty acids, on the other hand, were all highly active against the enveloped viruses, although the fatty acid concentration required for maximum viral inactivation varied by as much as 20-fold. Monoglycerides of these fatty acids were also highly antiviral, in some instances at a concentration 10 times lower than that of the free fatty acids. None of the fatty acids inactivated poliovirus. Antiviral fatty acids were found to affect the viral envelope, causing leakage and at higher concentrations, a complete disintegration of the envelope and the viral particles. They also caused disintegration of the plasma membranes of tissue culture cells resulting in cell lysis and death. The same phenomenon occurred in cell cultures incubated with stored antiviral human milk. The antimicrobial effect of human milk lipids in vitro is therefore most likely caused by disintegration of cellular and viral membranes by fatty acids. Studies are needed to establish whether human milk lipids have an antimicrobial effect in the stomach and intestines of infants and to determine what role, if any, they play in protecting infants against gastrointestinal infections.",,"['Thormar, H', 'Isaacs, C E', 'Brown, H R', 'Barshatzky, M R', 'Pessolano, T']",,,,
,PMC,The kinetics-based enzyme-linked immunosorbent assay for coronavirus antibodies in cats: calibration to the indirect immunofluorescence assay and computerized standardization of results through normalization to control values.,,PMC1255274,,,"The computer-assisted, kinetics-based enzyme-linked immunosorbent assay for coronavirus antibodies in cats was calibrated to the conventional indirect immunofluorescence assay by linear regression analysis and computerized interpolation (generation of ""immunofluorescence assay-equivalent"" titers). Procedures were developed for normalization and standardization of kinetics-based enzyme-linked immunosorbent assay results through incorporation of five different control sera of predetermined (""expected"") titer in daily runs. When used with such sera and with computer assistance, the kinetics-based enzyme-linked immunosorbent assay minimized both within-run and between-run variability while allowing also for efficient data reduction and statistical analysis and reporting of results.",,"['Barlough, J E', 'Jacobson, R H', 'Downing, D R', 'Lynch, T J', 'Scott, F W']",,,,
,PMC,Genetic resistance to mouse hepatitis virus correlates with absence of virus-binding activity on target tissues.,,PMC255233,,,"The molecular mechanism of genetic resistance of inbred mouse strains to mouse hepatitis virus, a murine coronavirus, was studied by comparing virus binding to plasma membranes of intestinal epithelium or liver from susceptible BALB/c and resistant SJL/J mice with a new solid-phase assay for virus-binding activity. Virus bound to isolated membranes from susceptible mice, but not to membranes from resistant mice. F1 progeny of SJL/J X BALB/c mice had an intermediate level of virus-binding activity on their enterocyte and hepatocyte membranes. This correlated well with previous studies showing that susceptibility to mouse hepatitis virus strain A59 is controlled by a single autosomal dominant gene (M. S. Smith, R. E. Click, and P. G. W. Plagemann, J. Immunol. 133:428-432). Because virus binding was not prevented by treating membranes with sodium dodecyl sulfate, the virus-binding molecule could be identified by a virus overlay protein blot assay. Virus bound to a single broad band of Mr 100,000 to 110,000 in membranes from hepatocytes or enterocytes of susceptible BALB/c and semisusceptible C3H mice, but no virus-binding band was detected in comparable preparations of resistant SJL/J mouse membranes. Therefore, SJL/J mice may be resistant to mouse hepatitis virus A59 infection because they lack a specific virus receptor which is present on the plasma membranes of target cells from genetically susceptible BALB/c and semisusceptible C3H mice.",,"['Boyle, J F', 'Weismiller, D G', 'Holmes, K V']",,,,
,PMC,Diarrheal response of gnotobiotic pigs after fetal infection and neonatal challenge with homologous and heterologous human rotavirus strains.,,PMC253357,,,"Pigs exposed in utero to human rotavirus (HRV) strain Wa serotype 1 from 15 to 36 days prior to birth responded immunologically by modifying their clinical response to neonatal oral challenge with a pathogenic dose of homologous Wa or heterologous M serotype 3 HRV. In these cases, diarrhea was prevented in 12 of 14 pigs and greatly reduced in the other two. However, fecal virus shedding was not significantly modified, since it was detected in 12 of 14 pigs. These results suggest the existence of a closer antigenic relationship between these two different HRV serotypes which may only be expressed in an in vivo test system. Exposure of fetal pigs to HRV DS-1 serotype 2 failed to cause infection or to induce any protection when pigs were challenged at birth with HRV Wa. This model for cross-protection studies in gnotobiotic piglets offers good possibilities for the evaluation of potential HRV vaccine candidates, for the in vivo study of antigenic similarities between rotavirus serotypes, and for the understanding of protective immune responses against diarrhea and virus shedding.",,"['Torres, A', 'Ji-Huang, L']",,,,
,PMC,Identification of two epitopes in the carboxyterminal 15 amino acids of the E1 glycoprotein of mouse hepatitis virus A59 by using hybrid proteins.,,PMC253324,,,"cDNA fragments coding for the carboxy terminus of the E1 envelope glycoprotein from mouse hepatitis virus A59, a coronavirus, were cloned into the bacterial expression vector pEX. Clones expressing E1 antigenic determinants were selected with a polyclonal anti-E1 antibody and used for immunization of rabbits and for affinity purification of existing polyclonal antisera. Immunofluorescence testing and immunoperoxidase labeling of coronavirus-infected cells showed that these reagents were monospecific for E1. In addition, by using hybrid proteins containing different lengths of the E1 carboxy terminus to affinity-purify a polyclonal antiserum against E1, we have been able to define two epitopes within the last 15 amino acid residues of the protein. These epitope-specific antibodies bind to E1 in Golgi and perinuclear membranes as well as to budding viruses; they do not, however, label the plasma membrane or the membranes of post-Golgi vesicles transporting virions to the cell surface.",,"['Tooze, S A', 'Stanley, K K']",,,,
,PMC,Cryptosporidium spp. and cryptosporidiosis.,,PMC373083,,,,,"['Fayer, R', 'Ungar, B L']",,,,
,PMC,Remission of diarrhoea due to cryptosporidiosis in an immunodeficient child treated with hyperimmune bovine colostrum.,,PMC1342109,,,"A boy aged 6 months who presented with poor weight gain, diarrhoea, and infection with Pneumocystis carinii was found to have congenital hypogammaglobulinaemia, which did not improve despite monthly treatment with intravenous gammaglobulin. At the age of 3 years and 2 months he developed severe vomiting and diarrhoea due to cryptosporidiosis, which failed to respond to conventional treatment. Infusion of hyperimmune bovine colostrum produced against parasite antigen, given by nasogastric tube, was started after symptoms had persisted for three weeks. His vomiting and diarrhoea resolved within five days of treatment, and oocysts were no longer seen in the stools after eight days. Later, however, he developed a rare complication, and oocysts were found in the common bile duct. Hyperimmune bovine colostrum may be useful in the treatment of many patients with immunodeficiency disorders.",,"['Tzipori, S', 'Roberton, D', 'Chapman, C']",,,,
,PMC,"Selective tropism of a neurotropic coronavirus for ependymal cells, neurons, and meningeal cells.",,PMC288928,,,"The ability of a neurotropic virus, mouse hepatitis virus type 3 (MHV3), to invade the central nervous system (CNS) and to recognize cells selectively within the brain was investigated in vivo and in vitro. In vivo, MHV3 induced in C3H mice a genetically controlled infection of meningeal cells, ependymal cells, and neurons. In vitro, purified MHV3 bound to the surface of isolated ependymal cells and cultured cortical neurons but not to oligodendrocytes or cultured astrocytes. MHV3 replicated within cultured cortical neurons and neuroblastoma cells (NIE 115); infected cultured neurons nonetheless survived and matured normally for a 7-day period postinfection. On the other hand, MHV3 had a low affinity for cortical glial cells or glioma cells (C6 line), both of which appear to be morphologically unaltered by viral infection. Finally, MHV3 infected and disrupted cultured meningeal cells. This suggests that differences in the affinity of cells for MHV3 are determinants of the selective vulnerability of cellular subpopulations within the CNS. In vivo, a higher titer of virus was needed for CNS penetration in the genetically resistant (A/Jx) mice than in the susceptible (C57/BL6) mouse strain. However, in spite of viral invasion, no neuropathological lesions developed. In vitro viral binding to adult ependymal cells of susceptible and resistant strains of mice was identical. Genetic resistance to MHV3-CNS infection appeared to be mediated both by a peripheral mechanism limiting viral penetration into the CNS and by intra-CNS mechanisms, presumably at a stage after viral attachment to target cells.",,"['Tardieu, M', 'Boespflug, O', 'Barbé, T']",,,,
,PMC,The nucleotide sequence of the extreme 5' end of the avian coronavirus genome; implications for the discontinuous mRNA synthesis.,,PMC311800,,,,,"['Bredenbeek, P J', 'Noten, J F', 'Lenstra, J A', 'Horzinek, M C', 'van der Zeijst, B A', 'Spaan, W J']",,,,
,PMC,Morphologic evaluation of the effects of Shiga toxin and E coli Shiga-like toxin on the rabbit intestine.,,PMC1888447,,,"The effects of a Shiga toxin derived from Shigella dysenteriae Type 1, Strain 60R, and a Shiga-like toxin from the enterohemorrhagic Escherichia coli O157:H7, Strain 933, were studied in the in vivo rabbit ileal loop model. The effects of both toxins were similar and resulted in severe villus blunting by 18-24 hours after exposure. With both toxins, a dose effect was noted; and the lesions, first detected at 2 hours after inoculation, became more severe over time. Both toxins appeared to act directly and selectively on the mature columnar absorptive epithelium of the intestinal villus, which resulted in the premature expulsion of these cells from the lateral villus wall, with a decrease in the villus/crypt ratio. The goblet mucous cells remained attached and frequently formed clusters on the blunt villus apices. The crypt epithelium underwent a rapid proliferation and maintained the epithelial integrity. The ultrastructural changes observed in the toxin-injured villus absorptive cells suggested that these cells underwent a process of apoptosis, rather than necrosis. These findings suggest that both toxins act in vivo in the small intestine on a specific cell population, the mature, differentiated absorptive villus epithelium.",,"['Keenan, K. P.', 'Sharpnack, D. D.', 'Collins, H.', 'Formal, S. B.', ""O'Brien, A. D.""]",,,,
,PMC,Enteric coronavirus in symptomless homosexuals.,,PMC500245,,,,,"['Riordan, T', 'Curry, A', 'Bhattacharyya, M N']",,,,
,PMC,Critical epitopes in transmissible gastroenteritis virus neutralization.,,PMC253910,,,"Purified transmissible gastroenteritis (TGE) virus was found to be composed of three major structural proteins having relative molecular weights of 200,000, 48,000, and 28,000. The peplomer glycoprotein was purified by affinity chromatography with the monoclonal antibody (MAb) 1D.G3. A collection of 48 MAbs against TGE virus was developed from which 26, 10, and 3 were specific for proteins E2, N, and E1, respectively. A total of 14 neutralizing MAbs of known reactivity were E2 protein specific. In addition, MAb 1B.C11, of unknown specificity, was also neutralizing. These MAbs reduced the virus titer 10(2)- to 10(9)-fold. Six different epitopes critical in TGE virus neutralization were found, all of which were conformational based on their immunogenicity and antigenicity. Only the epitope defined by MAb 1G.A7 was resistant to sodium dodecyl sulfate treatment, although it was destroyed by incubation in the presence of both the detergent and beta-mercaptoethanol. The frequency of MAb-resistant (mar) mutants selected with four MAbs (1G.A7, 1B.C11, 1G.A6, and 1E.F9) ranged from 10(-6) to 10(-7), whereas the frequency of the putative mar mutant defined by MAb 1B.B11 was lower than 10(-9). Furthermore, the epitopes defined by these MAbs and by MAbs 1H.C2 and 1A.F10, were present in 11 viral isolated with different geographical locations, years of isolation, and passage numbers (with the exception of two epitopes absent or modified in the TOY 56 viral isolate), suggesting that the critical epitopes in TGE virus neutralization were highly conserved.",,"['Jiménez, G', 'Correa, I', 'Melgosa, M P', 'Bullido, M J', 'Enjuanes, L']",,,,
,PMC,Translation and processing of mouse hepatitis virus virion RNA in a cell-free system.,,PMC253896,,,"The first event after infection with mouse hepatitis virus strain A59 (MHV-A59) is presumed to be the synthesis of an RNA-dependent RNA polymerase from the input genomic RNA. The synthesis and processing of this putative polymerase protein was studied in a cell-free translation system utilizing 60S RNA from MHV-A59 virions. The polypeptide products of this reaction included two major species of 220 and 28 kilodaltons. Kinetics experiments indicated that both p220 and p28 appeared after 60 min of incubation and that protein p28 was synthesized initially as the N-terminal portion of a larger precursor protein. When the cell-free translation products were labeled with N-formyl[35S]methionyl-tRNAi, p28 was the predominant radioactive product, confirming its N-terminal location within a precursor protein. Translation in the presence of the protease inhibitors leupeptin and ZnCl2 resulted in the disappearance of p28 and p220 and the appearance of a new protein, p250. This product, which approached the maximal size predicted for a protein synthesized from genomic RNA, was not routinely detected in the absence of inhibitors even under conditions which optimized the translation reaction for elongation of proteins. Subsequent chelation of ZnCl2 resulted in the partial cleavage of the precursor protein and the reappearance of p28. One-dimensional peptide mapping with Staphylococcus aureus V-8 protease confirmed the precursor-product relationship of p250 and p28. The results show that MHV virion RNA, like many other viral RNAs, is translated into a large polyprotein, which is cleaved soon after synthesis into smaller, presumably functional proteins. This is in marked contrast to the synthesis of other MHV proteins, in which minimal proteolytic processing occurs.",,"['Denison, M R', 'Perlman, S']",,,,
,PMC,"In vitro antiviral activity of the 6-substituted 2-(3',4'-dichlorophenoxy)-2H-pyrano[2,3-b]pyridines MDL 20,610, MDL 20,646, and MDL 20,957.",,PMC180594,,,"The 6-substituted 2-(3',4'-dichlorophenoxy)-2H-pyrano[2,3-b]pyridines MDL 20,610 (6-SO2CH3), MDL 20,646 (6-Br), and MDL 20,957 (6-Cl) are potent antirhinovirus compounds with median plaque 50% inhibitory concentrations (IC1/2s) of 0.03, 0.006, and 0.006 micrograms/ml, respectively, against the 32 serotypes evaluated. The 6-halogenated analogs produced 99% reductions in progeny virion yields at concentrations as low as 0.004 micrograms/ml. However, these analogs perturbated HeLa cell metabolism at lower concentrations (at or above 5 micrograms/ml) than did the 6-methylsulfonyl analog (at or above 20 micrograms/ml). Compound MDL 20,610 was also active against human, simian, and bovine rotaviruses (cytopathic effect IC1/2s of 0.8 to 1.5 micrograms/ml) and possessed variable enterovirus and paramyxovirus activity.",,"['Kenny, M T', 'Dulworth, J K', 'Bargar, T M', 'Torney, H L', 'Graham, M C', 'Manelli, A M']",,,,
,PMC,Distempter Vaccination of Dogs: Factors Which Could Cause Vaccine Failure,,PMC1680307,,,"Distemper vaccination failures are uncommon. A number of factors which could cause such failure are discussed. The blocking effect of maternal antibody can be expected in 50% of pups at six weeks but is not important after 12 weeks. Among intercurrent infections, the immunosuppressive effect of parvovirus has the potential to precipitate vaccine-induced distemper. Corticosteroids at levels up to 10 mg/kg do not interfere with successful distemper vaccination. Anesthesia or surgery has little effect but use of chloramphenicol or tetracyclines should be avoided. High environmental temperatures can lead to vaccine failure, as can vitamin E deficiency. Excessive environmental exposure to virulent distemper virus can overcome levels of protection which would be adequate under normal circumstances.",,"Povey, R. Charles",,,,
,PMC,Coronavirus MHV-JHM: nucleotide sequence of the mRNA that encodes the membrane protein.,,PMC311641,,,,,"['Pfleiderer, M', 'Skinner, M A', 'Siddell, S G']",,,,
,PMC,Antibody dependent cellular cytotoxicity against coronavirus 229E-infected cells.,,PMC2013047,,,"An antibody dependent cellular cytotoxic (ADCC) reaction was elicited using human mixed lymphocyte cultures against coronavirus 229E-infected C-16 cells. The response was assayed in microtitre plates by radioactive chromium release. Optimal killing of target cells was achieved using cells labelled 22 h after infection. A prozone was present and the optimal dilution of sera was invariably 1:200. The majority (70%) of sera tested gave a positive ADCC response. These included all sera judged positive by ELISA, but also some which were judged negative. Two experiments using purified IgG from serum which was ADCC and ELISA positive suggested that the response is mediated by an IgG antibody and that the prozone is due to a separate serum component.",,"['Holmes, M. J.', 'Callow, K. A.', 'Childs, R. A.', 'Tyrrell, D. A.']",,,,
,PMC,Natural and experimental infection with an attaching and effacing strain of Escherichia coli in calves.,,PMC260880,,,"Gnotobiotic calves were inoculated with an O5:K4:H-, urease-positive strain of Escherichia coli isolated from a 2-day-old calf with diarrhea. The calves developed elevated temperatures and passed loose mucoid feces, with or without blood. The E. coli strain was negative for heat-stable and heat-labile enterotoxins but produced high levels of Shiga-like toxin. Bacteria attached diffusely to the epithelium of the large intestine and multifocally to the epithelium of the ileum. The duodenum and jejunum were not affected. At the sites of bacterial attachment, microvilli were effaced, enterocytes were degenerate, and necrosis and exfoliation had occurred. These results confirm a previous report from England that calves may naturally contract infections similar to those caused by enteropathogenic E. coli strains pathogenic to humans or rabbits. This suggests that the calf bacterial strains, like some enteropathogenic E. coli strains, produce high levels of Shiga-like toxin and cause attachment and effacement lesions in the colonic epithelium of the infected host.",,"['Moxley, R A', 'Francis, D H']",,,,
,PMC,Site-specific alteration of murine hepatitis virus type 4 peplomer glycoprotein E2 results in reduced neurovirulence.,,PMC253097,,,"Strains of the murine coronavirus mouse hepatitis virus type 4 (MHV-4) which contained a mutation in the E2 peplomer glycoprotein were obtained by selection for resistance to neutralization by monoclonal antibodies. Characterization of six variants representing two independent epitopes on E2, E2B and E2C, by in vitro neutralization and antibody-binding assays demonstrated that selection for an alteration in epitope E2B also resulted in changes in epitope E2C and vice versa. We observed a mutation frequency of approximately 10(-4.3) to 10(-4.6), which is consistent with the expected occurrence of single point mutations. The variant virus strains were attenuated with respect to neurovirulence when compared with wild-type MHV-4. Mice normally develop encephalomyelitis and die after wild-type MHV-4 infection. Mice receiving 2- to 3-log-higher doses of the variant strains survived and developed demyelinating disease. As the disease progressed, evidence of remyelination and ongoing demyelination was observed up to 65 days after infection. Virus reisolated 15 days after infection retained the variant phenotype. The data indicate that the E2 glycoprotein plays a central role in determining the cellular tropism and virulence of MHV-4 in the mouse.",,"['Dalziel, R G', 'Lampert, P W', 'Talbot, P J', 'Buchmeier, M J']",,,,
,PMC,Nucleotide sequence encoding the membrane protein of the IBV strain 6/82.,,PMC311559,,,,,"['Binns, M M', 'Boursnell, M E', 'Tomley, F M', 'Brown, T D']",,,,
,PMC,Myocardial diseases of animals.,,PMC1888177,,,"In this review we have attempted a comprehensive compilation of the cardiac morphologic changes that occur in spontaneous and experimental myocardial diseases of animals. Our coverage addresses diseases of mammals and birds and includes these diseases found in both domesticated and wild animals. A similar review of the myocardial diseases in this broad range of animal species has not been attempted previously. We have summarized and illustrated the gross, microscopic, and ultrastructural alterations for these myocardial diseases; and, whenever possible, we have reviewed their biochemical pathogenesis. We have arranged the myocardial diseases for presentation and discussion according to an etiologic classification with seven categories. These include a group of idiopathic or primary cardiomyopathies recognized in man (hypertrophic, dilated, and restrictive types) and a large group of secondary cardiomyopathies with known causes, such as inherited tendency; nutritional deficiency; toxicity; physical injury and shock; endocrine disorders, and myocarditides of viral, bacterial, and protozoal causation. Considerable overlap exists between each of the etiologic groups in the spectrum of pathologic alterations seen in the myocardium. These include various degenerative changes, myocyte necrosis, and inflammatory lesions. However, some diseases show rather characteristic myocardial alterations such as vacuolar degeneration in anthracycline cardiotoxicity, myofibrillar lysis in furazolidone cardiotoxicity, calcification in calcinosis of mice, glycogen accumulation in the glycogenoses, lipofuscinosis in cattle, fatty degeneration in erucic acid cardiotoxicity, myofiber disarray in hypertrophic cardiomyopathy, and lymphocytic inflammation with inclusion bodies in canine parvoviral myocarditis. The myocardial diseases represent the largest group in the spectrum of spontaneous cardiac diseases of animals. Pericardial and endocardial diseases and congential cardiac diseases are seen less frequently; and, in contrast to man, coronary artery disease and myocardial ischemia are rather infrequent in animals. The present review shows clearly that the spectrum of myocardial diseases in animals is enlarging and that many newly recognized diseases are emerging and assuming considerable importance. For example, various heritable cardiomyopathies have recently been described in the KK mouse, cattle, and rats. Increasingly recognized myocardial diseases include cardiomyopathies in cats, dogs, and birds; anthracycline cardiotoxicity; furazolidone cardiotoxicity; ionophore cardiotoxicity; myocardial damage associated with central nervous system injuries; myocardial hypertrophy in",,"['Van Vleet, J. F.', 'Ferrans, V. J.']",,,,
,PMC,An epidemiological study of selected calf pathogens on Holstein dairy farms in southwestern Ontario.,,PMC1255218,,,"Fecal samples from calves on 78 randomly selected Holstein dairy farms in southwestern Ontario were screened for Salmonella, Campylobacter jejuni/coli, enteropathogenic Escherichia coli, rotavirus and coronavirus. Based on the observed prevalence, 22% of farms had calves infected with Salmonella, 13% with Campylobacter jejuni/coli, 41% with enteropathogenic E. coli, 19% with rotavirus and 5% with coronavirus. These estimates can be modified, using a method developed by Mullen and Prost (1983) for the World Health Organization, to account for the nature of the laboratory test used. If the test is assumed to have no false positives (that is, if an organism is detected it must be there), then the observed prevalence estimates seen on this study may greatly underestimate the true prevalence of infected premises. The use of nipple feeders for calves was associated with an increased probability of farms having calves shedding detectable fecal levels of Salmonella, E. coli, or one of the two viruses. The use of group pens was associated with an increased odds of finding C. jejuni. Calves with diarrhea on these farms tended to have increased odds of shedding rotavirus, and E. coli with the K99 antigen. However, at the farm level, none of the organisms was associated with above median levels of morbidity. Farms positive for one or other of the viruses had increased odds of experiencing calf mortality relative to virus-negative farms, and farms positive for C. jejuni/coli had decreased odds of mortality.(ABSTRACT TRUNCATED AT 250 WORDS)",,"['Waltner-Toews, D', 'Martin, S W', 'Meek, A H']",,,,
,PMC,Aetiological role of viruses in multiple sclerosis: a review.,,PMC1290380,,,,,"Larner, A J",,,,
,PMC,Protective effect of monoclonal antibodies on lethal mouse hepatitis virus infection in mice.,,PMC253053,,,"Neutralizing and nonneutralizing monoclonal antibodies to the peplomer glycoprotein and nucleocapsid protein of a mouse hepatitis virus (MHV), MHV-NuU, protected mice against lethal MHV-2 challenge. Histopathologically, livers of mice receiving protective antibodies showed some focal necrotic lesions with remarkable cellular infiltration instead of fulminant hepatitis caused by MHV-2.",,"['Nakanaga, K', 'Yamanouchi, K', 'Fujiwara, K']",,,,
,PMC,Postmortem findings in four litters of dogs with familial canine dermatomyositis.,,PMC1888266,,,"Postmortem evaluations were performed on 20 juvenile to young adult collie and collie-Labrador retriever crossbred dogs with dermatomyositis and 10 neonatal collies. Cutaneous, muscular, and vascular lesions were present in the juvenile and adult dogs and were most severe in areas of the head and distal extremities. In more severely affected dogs, lesions were more generalized, including myositis of esophageal muscle and arteritis of skin, muscle, bladder, and spermatic cord. Although viruses were not isolated from muscle, crystalline viral-like structures were present in cytoplasm of endothelial cells within skeletal muscle. The dogs with dermatitis and myositis consistently had lymphoid hyperplasia, especially of peripheral lymph nodes. More severely affected dogs were smaller than less severely affected littermates, and the more severely affected males had reduced weight of testicles and prostate glands, compared with body weight. The reduced weight of genital organs correlated positively with reduced fertility. A few lymphoid aggregates were present in or around thyroid glands of 6 of the 20 dogs. There was no histologic evidence of glomerular disease in any of the dogs. The neonatal collies had no evidence of dermatomyositis.",,"['Hargis, A. M.', 'Prieur, D. J.', 'Haupt, K. H.', 'Collier, L. L.', 'Evermann, J. F.', 'Ladiges, W. C.']",,,,
,PMC,"Excretion of faecal viruses during the first year of life including attendance at a day nursery in Lisbon, Portugal.",,PMC2129693,,,"In an attempt to determine the frequency of virus infections of the gastrointestinal tract, the duration of virus shedding in faeces and its relation to outbreaks of illness of any kind, faecal samples were collected from children attending a day nursery at a Lisbon institution. In this study, ten children were surveyed from their enrollment at the nursery, weekly specimens of faeces being collected over a period of 1 year. A total of 459 samples were obtained. In addition four of these children were also followed-up from their first week of life to their enrollment at the nursery, 79 samples being collected during this period. Viruses were detected in a high percentage (44.4%) of these stools, including strains of oral vaccine polioviruses together with viruses isolated in routine cell cultures and by electron microscopy (EM). These viruses were detected in both healthy and ill babies. The possible association between viruses isolated in cell cultures or detected by EM and illness was examined and the results show that the asymptomatic excretion of viruses is frequent, particularly in children within this age group.",,"['Avillez, M. F.', 'Paixão, M. T.']",,,,
,PMC,Intracellular assembly and packaging of hepatitis B surface antigen particles occur in the endoplasmic reticulum.,,PMC252996,,,"Hepatitis B surface antigen (HBsAg) particles are secreted by Chinese hamster ovary cells that are stably transfected with the S gene of hepatitis B virus. The assembly of HBsAg into cylindrical and spherical particles occurred intracellularly within the endoplasmic reticulum. HBsAg particles accumulated within large dilated areas of the endoplasmic reticulum and remained within these structures for most of the time prior to secretion from the cells. Once the particles were formed, the HBsAg polypeptides did not appear to become associated with subsequent intracellular organelle membranes or the plasma membrane. HBsAg within the dilated structures did not bind wheat germ agglutinin, indicating that its oligosaccharide chains had not yet been processed to the complex form (containing terminal sialic acid-N-acetylglucosamine residues). The oligosaccharide chains of HBsAg are processed to the complex form and can be detected on the HBsAg after secretion, but this event was not detected within cells. In addition, HBsAg was not observed on the cell surface by indirect immunofluorescence or immunoprecipitation, although immunoelectron microscopy revealed some staining at or near the cell surface. These results suggested that HBsAg was either secreted from cells without being incorporated into the plasma membrane, or that the levels of HBsAg in the plasma membrane were below the limits of detection.",,"['Patzer, E J', 'Nakamura, G R', 'Simonsen, C C', 'Levinson, A D', 'Brands, R']",,,,
,PMC,Pathogenicity of antigenic variants of murine coronavirus JHM selected with monoclonal antibodies.,,PMC252994,,,"To analyze the pathogenesis of the neurotropic murine coronavirus JHMV, we used monoclonal antibodies to the E2 viral glycoprotein to select antigenic variant viruses. Monoclonal antibodies J.7.2 and J.2.2 were shown to bind to topographically distinct regions of the E2 molecule, and the variants selected with the two antibodies demonstrated very different disease pictures in mice. Variants selected with J.7.2 were, like the parental virus, highly virulent and caused an acute encephalitic illness. By contrast, J.2.2-selected variants predominantly caused a subacute paralytic disease clinically and extensive demyelination histologically. Antigenic differences among the variants and parental virus were readily demonstrable with anti-E2 monoclonal antibodies. However, no differences between the viruses could be shown in binding studies with monoclonal antibodies directed against either E1 or N, the other two JHMV structural proteins. Since only J.2.2 selected demyelinating variants with reduced neurovirulence, it is likely that this monoclonal antibody recognizes a subregion of the E2 molecule that is particularly important in JHMV pathogenesis.",,"['Fleming, J O', 'Trousdale, M D', 'el-Zaatari, F A', 'Stohlman, S A', 'Weiner, L P']",,,,
,PMC,Immunological Comparisons of Nitrate Reductase of Different Plant Species Using Monoclonal Antibodies,,PMC1075343,,,"Six monoclonal antibodies against different epitopes of maize leaf nitrate reductase were used to compare plant nitrate reductases in enzyme linked immunosorbent assay and enzyme activity inhibition tests. The number of cross-reacting antibodies was shown to vary with species according to phylogenetic classification, ranging from five (sugarcane) to one (dicotyledonous species). Cross-reactions were restricted to higher plant nitrate reductases.",,"['Cherel, Isabelle', 'Marion-Poll, Annie', 'Meyer, Christian', 'Rouze, Pierre']",,,,
,PMC,Leader sequences of murine coronavirus mRNAs can be freely reassorted: evidence for the role of free leader RNA in transcription.,,PMC323700,,,"Mouse hepatitis virus (MHV), which replicates in cytoplasm of infected cells, contains an identical leader RNA sequence at the 5' end of each of the virus-specific mRNAs. Previous studies suggested that the synthesis of these mRNAs does not involve conventional RNA splicing and may instead require priming by a free leader RNA. In this communication, we demonstrate that, during a mixed infection with two different MHVs, the leader RNA sequences from one virus could be detected on the mRNAs of the coinfecting virus at a high frequency, as if the leader sequence and mRNAs were joined together from two randomly segregating RNA segments. This finding demonstrates that MHV mRNA transcription utilizes independently transcribed leader RNA species that possess the trans-acting property. This study thus provides further evidence in support of the unique model of ""leader-primed transcription"" for coronavirus mRNA synthesis.",,"['Makino, S', 'Stohlman, S A', 'Lai, M M']",,,,
,PMC,Interfering with the real cold.,,PMC1340425,,,,,"Scott, G",,,,
,PMC,Relationships between rotavirus diarrhea and intestinal microflora establishment in conventional and gnotobiotic mice.,,PMC268738,,,"Intestinal microflora did not play a role in the intensity or course of EDIM rotavirus-induced diarrhea, since similar results were observed in axenic and conventional mice. In conventional mice, rotavirus-induced diarrhea did not modify the establishment of Lactobacillus spp. and Escherichia coli before weaning. The consequences of diarrhea on the establishment of strictly anaerobic bacteria after weaning were studied through the measurement of two bacterial functions, the microbial barrier effect against E. coli and the development of the immunoglobulin A intestinal immune system. These two bacterial functions were expressed in a similar way in diarrheic and control mice. In young gnotobiotic mice inoculated with Clostridium perfringens or C. difficile, rotavirus infection led to an earlier development of both strains, as compared with controls. This effect was more pronounced with C. difficile. These results suggest that rotavirus infections might enhance opportunistic bacterial infections.",,"['Moreau, M C', 'Corthier, G', 'Muller, M C', 'Dubos, F', 'Raibaud, P']",,,,
,PMC,Jejunal myoelectrical activity in the conscious neonatal pig.,,PMC1182724,,,"The purpose of this study was to define and quantify patterns of normal jejunal myoelectrical activity in the conscious neonatal pig. Twelve 3-day-old piglets were obtained from a local herd. At 7 days of age four bipolar Ag-AgCl electrodes were surgically implanted at 5 cm intervals on the jejunum. Piglets were divided into fed (n = 7) and fasted (n = 5) groups and a minimum of four daily recordings were made from each pig between 7 and 14 days of age. Slow wave and spike activity were seen in all animals. Slow waves occurred at a frequency of 17.0 +/- 0.3 cycles/min (c.p.m.) in fed and 16.8 +/- 0.2 c.p.m. in fasted piglets. Spike activity predominated, occurring in characteristic migrating myoelectrical complexes (m.m.c.s.) and occupying 79% of the recording time in fed and 73% in fasted piglets (P less than 0.05). The activity front (phase 3) of the m.m.c. recurred every 47.7 +/- 2.4 min in fed, and 50.9 +/- 2.3 min in fasted piglets. The m.m.c. periodicity in both groups was irregular, with a range of 4-145 min in fed, and 8-104 min in fasted piglets. Activity fronts lasted 4.8 +/- 0.1 min in fed and 4.4 +/- 0.1 min in fasted piglets. All piglets demonstrated intense, short (2.5-5.0 s), distinct bursts of intense spike activity (migrating action potential complexes, m.a.p.c.s.). These were rapidly conducted in an aboral direction at a velocity of 1.8 cm/s in fed, and 0.8 cm/s in fasted piglets (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)",,"['Burrows, C F', 'Merritt, A M', 'Tash, J']",,,,
,PMC,RNA-binding proteins of bovine rotavirus.,,PMC252945,,,"Two major bovine rotavirus proteins have RNA-binding activity as shown by an RNA overlay-protein blot assay. Of the six proteins in purified virions, only one showed RNA-binding activity. This 92,000-molecular-weight (92K) protein was present in both single- and double-shelled particles. Its RNA-binding activity was blocked by preincubation with monospecific antibody to VP2. Thus, the 92K RNA-binding protein in rotavirus virions is VP2, the second most abundant protein in single-shelled particles. In infected cell extracts, numerous cellular RNA-binding proteins and two virus-specific RNA-binding proteins were detected, VP2 and a 31K nonstructural (NS31) protein. VP2 bound single-stranded RNA in preference to double-stranded RNA, whereas NS31 bound both single- and double-stranded RNA equally well. Binding did not appear to be nucleotide sequence specific, because RNA from uninfected cells and an unrelated RNA virus bound to VP2 and to NS31 as did rotavirus RNA. This technique showed that both cellular and rotavirus RNA-binding proteins also bound DNA. VP2 interacted with rotavirus RNA over a broad pH range, with an optimum at pH 6.4 to 6.8, and at NaCl concentrations between 0 and 100 mM. The RNA-binding activity of NS31 exhibited similar pH and NaCl dependency. Sequence-specific nucleic acid binding could be detected by this method. When labeled synthetic oligodeoxyribonucleotides corresponding to the 3' and 5' plus-sense terminal sequences of rotavirus gene segments were used as probes, the 3' synthetic oligodeoxyribonucleotide bound to one 48K protein in control and infected cells. This suggests that there may be a specific functional interaction between the 48K cellular protein and this 3'-terminal noncoding region of the rotavirus genome or mRNA. These data show that the RNA overlay-protein blot assay is a useful test to identify some cellular and viral proteins with RNA-binding activity. For bovine rotavirus, the evidence suggests that, of all the virus-specific proteins, VP2 and NS31 are most likely to interact with RNA during transcription and replication or virus assembly or both.",,"['Boyle, J F', 'Holmes, K V']",,,,
,PMC,Restricted replication of mouse hepatitis virus A59 in primary mouse brain astrocytes correlates with reduced pathogenicity.,,PMC252928,,,"Temperature-sensitive (ts) mutants of mouse hepatitis virus A59 (MHV-A59) are drastically attenuated in their pathogenic properties. Intracerebral inoculation of mice with 10(5) PFU of mutant ts342 results in prolonged infection of the central nervous system, whereas 100 PFU of wild-type virus are lethal (M. J. M. Koolen, A. D. M. E. Osterhaus, G. van Steenis, M. C. Horzinek, and B. A. M. van der Zeijst, Virology 125:393-402, 1983). In the Sac(-) cell line ts342 grows as well at 37 degrees C (the body temperature of mice) as at 31 degrees C (the permissive temperature). There is, however, a difference in primary cultures of mouse brain astrocytes. After infection with ts342, astrocytes produced low levels of infectious virus (5.2 +/- 3.7%) compared with virus yields after infection with wild-type virus. The fraction of wild-type virus- and ts342-infected cells was similar. Electron microscopy showed in wild-type virus-infected cells abundant virions in smooth vesicles usually closely associated with a well-developed Golgi apparatus. In mutant-infected cells no mature ts342 virus particles were found. There was no difference between ts342 and wild-type virus regarding the intracellular virus-specific RNAs. In ts342-infected cells the viral glycoproteins E2 and E1 were not detectable or were barely detectable. Either the mRNAs for the glycoproteins are not translated or the proteins are rapidly broken down. Revertants of ts342 were isolated. They grew as well as wild-type virus in astrocytes, indicating that they apparently produced sufficient amounts of E2 and E1, the ts defect itself rather than a second site mutation is responsible for the defect in replication, and the ts defect acts in unison with host-cell factors. The revertants also regained the lethal properties of wild-type virus.",,"['van Berlo, M F', 'Wolswijk, G', 'Calafat, J', 'Koolen, M J', 'Horzinek, M C', 'van der Zeijst, B A']",,,,
,PMC,Infectious bronchitis virus RNA D encodes three potential translation products.,,PMC339728,,,,,"['Niesters, H G', 'Zijderveld, A J', 'Seifert, W F', 'Lenstra, J A', 'Bleumink-Pluym, N M', 'Horzinek, M C', 'van der Zeijst, B A']",,,,
,PMC,Infection with Cryptosporidium spp. in humans and cattle in Manitoba.,,PMC1255185,,,"Between October 1, 1983 and October 31, 1984, fecal specimens from 3656 persons with enteritis and 182 calves, representing 148 herds having a neonatal diarrhea problem, were examined for oocysts of Cryptosporidium spp. Oocysts were found in 1% of human and 25% of bovine specimens. All infected persons were immunocompetent. Children under five years of age had an infection rate of 25/100,000 compared to 1.4/100,000 in older people (p less than 0.005). Rates in northern communities were four to seven times as high as those in southern Manitoba. Human infections occurred most commonly in late summer and fall. In beef calves infection occurred in winter and spring, the calving season in Manitoba. Epidemiological association between the infection in people and in cattle could not be established.",,"['Mann, E D', 'Sekla, L H', 'Nayar, G P', 'Koschik, C']",,,,
,PMC,Variation in virulence of bovine rotaviruses.,,PMC2129655,,,"Forty-six gnotobiotic calves aged less than 16 days or 42-116 days were infected with three strains of bovine rotavirus designated C3-160, CP-1 and PP-1. Each virus was passaged and cloned in cell culture (cloned viruses) but CP-1 and PP-1 were also used before culture (faecal viruses). Infection of calves aged less than 16 days with faecal or cloned CP-1 caused disease whereas cloned C3-160 and faecal or cloned PP-1 caused subclinical infections. The clinical signs of disease were change in faecal colour to pale yellow or cream, increase of 2- to 7-fold in the volume of faecal output and, usually, anorexia. With the virulent CP-1 virus and the avirulent C3-160, similar amounts of virus were excreted in the faeces for 4-6 days. Infection of calves aged 56-116 days with faecal CP-1 produced disease of similar severity to that seen in calves aged 7-10 days infected with the same virus. No differences in clinical signs, virus excretion or levels of convalescent antibody were seen between the two groups. With cloned CP-1, 5 of 8 older calves developed disease but 3 showed only mild signs of infection. It was concluded that two strains of rotavirus caused sub-clinical infections in young calves while a third was virulent in calves up to at least 116 days of age.",,"['Bridger, J. C.', 'Pocock, D. H.']",,,,
,PMC,Viruses and Demyelinating Diseases,,PMC1680146,,,,,"Orr, J. P.",,,,
,PMC,Characterization and translation of transmissible gastroenteritis virus mRNAs.,,PMC252834,,,"Three protein species were identified in purified transmissible gastroenteritis virus particles (strain Purdue). They are thought to represent constituents of the peplomer (E2; molecular weights of 280,000 and 240,000), the envelope (E1; molecular weights of 28,000, 31,500, and 33,000), and the nucleocapsid (N; molecular weight of 48,000). In infected cells, proteins with molecular weights of 195,000 (E2), 48,000 (N), and 28,000 (E1) were detected. Tunicamycin, an inhibitor of N glycosylation, prevented the appearance of polypeptides with molecular weights of 195,000 and 28,000 in infected cells; instead, proteins with molecular weights of 160,000 and 25,000 were observed. One minor and five major mRNA species were detected in porcine cells after infection. Their size was determined to be 23.6 kilobases (kb) (RNA1), 8.4 kb (RNA3), 3.8 kb (RNA4), 3.0 kb (RNA5), 2.6 kb (RNA6), and 1.9 kb (RNA7). The RNAs were translated in vitro. RNA7 was shown to code for the N protein. Although complete separation of RNA6 could not be achieved, it was shown to encode an unglycosylated (molecular weight of 25,000) precursor of E1 (molecular weight of 28,000). RNA4 was translated into a nonstructural protein with a molecular weight of 24,000. Translation of RNA3 resulted in proteins with molecular weights of 250,000 and 130,000 and smaller molecules which could be precipitated with a monoclonal antibody directed against E2.",,"['Jacobs, L', 'van der Zeijst, B A', 'Horzinek, M C']",,,,
,PMC,High-frequency RNA recombination of murine coronaviruses.,,PMC252799,,,"The RNA genome of coronaviruses consists of a single species of nonsegmented RNA. In this communication, we demonstrate that the RNA genomes of different strains of murine coronaviruses recombine during mixed infection at a very high frequency. Susceptible cells were coinfected with a temperature-sensitive mutant of one strain of mouse hepatitis virus (MHV) and a wild-type virus of a different strain. Of 21 randomly isolated viruses released from the coinfected cells at the nonpermissive temperature, 2 were recombinants which differed in the site of recombination. After three serial passages of the original virus pool derived from the mixed infection, the majority of the progeny viruses were recombinants. These recombinant viruses represented at least five different recombination sites between the two parental MHV strains. Such a high-frequency recombination between nonsegmented RNA genomes of MHV suggests that segmented RNA intermediates might be generated during MHV replication. We propose that the RNA replication of MHV proceeds in a discontinuous and nonprocessive manner, thus generating free segmented RNA intermediates, which could be used in RNA recombination via a copy-choice mechanism.",,"['Makino, S', 'Keck, J G', 'Stohlman, S A', 'Lai, M M']",,,,
,PMC,La gestion sanitaire des élevages de rongeurs utilisés en recherche biomédicale: III. Le programme de surveillance des infections,,PMC1680196,,,HEALTH SURVEILLANCE PROGRAM: This article outlines the principal components of quality control of laboratory rodents.,,,,,,
,PMC,La gestion sanitaire des élevages de rongeurs utilisés en recherche biomédicale: I. La nécessité de disposer d'animaux homogènes dans leur réaction,,PMC1680183,,,THE NECESSITY FOR THE DISPOSAL OF HOMOGENEOUS REACTING ANIMALS: This paper points out the principal factors that may influence the course of experimentation using laboratory animals. Particular attention is given to extrinsic factors and to infectious agents.,,"Lussier, G.",,,,
,PMC,Viruses and Demyelinating Diseases,,PMC1028703,,,,,"Compston, Alastair",,,,
,PMC,Relation between genomic and capsid structures in RNA viruses.,,PMC339422,,,"We described a new computer program for calculation of RNA secondary structure. Calculation of 20 viral RNAs with this program showed that genomes of the icosahedral capsid viruses had higher folding probabilities than those of the helical capsid viruses. As this explains virus assembly quite well, the information of capsid structure must be imprinted not only in the capsid protein structures but also in the base sequence of the whole genome. We compared folding probability of the original sequence with that of the random sequence in which base composition was the same as the original. All the actual genomes of RNA viruses were more folded than the corresponding random sequences, even though most transcripts of chromosomal genes tended to be less folded. The data can be related to encapsidation of viral genomes. It was thus suggested that there exists a relation between actual sequences and random sequences with the same base ratios, and that the base ratio itself has some evolutional meaning.",,"['Yamamoto, K', 'Yoshikura, H']",,,,
,PMC,"Single-radial-haemolysis test for diagnosing flavivirus infections, particularly Japanese encephalitis",,PMC2490953,,,"Use of the single-radial-haemolysis (SRH) technique for the diagnosis of flavivirus infections is described. A large number of paired and single convalescent serum samples collected from cases of encephalitis during two major outbreaks in Kolar district of Karnataka State in India during 1977 and 1979 were tested by this technique. The results were compared with those obtained in the haemagglutination inhibition (HI) test in all cases, and the complement fixation (CF) and neutralization tests in some cases. Japanese encephalitis virus was shown by the SRH test to be the major etiologic agent responsible for both epidemics. This was corroborated by the HI, CF and neutralization test results. The single-radial-haemolysis test was found to be simpler and more specific and sensitive than the haemagglutination inhibition test.",,"['George, Samuel', 'Pavri, Khorshed']",,,,
,PMC,Distinct serotypes of porcine rotavirus associated with diarrhea in suckling piglets in southern Quebec.,,PMC1255175,,,"Cytopathic rotavirus strains were isolated in cell cultures from the intestinal contents of diarrheic piglets on Quebec pig farms where repeated outbreaks of enteritis occurred. All the isolates shared the common group antigens of rotaviruses as revealed by immunofluorescence and counterimmunoelectrophoresis. A hemagglutinating activity was demonstrated with human group O, porcine and guinea pig erythrocytes. At least one of the isolates was clearly distinguished from the American prototype of porcine rotavirus (strain OSU) by neutralization and hemagglutination inhibition tests; a third serotype was also suspected. By polyacrylamide gel electrophoresis of RNA, it was not possible to differentiate these isolates.",,"['Dea, S', 'Elazhary, M A', 'Roy, R S']",,,,
,PMC,Genomic variations and antigenic relationships among cytopathic rotavirus strains isolated in Quebec dairy herds.,,PMC1255174,,,"Twelve isolates of bovine rotavirus, originating from eight dairy herds in Quebec known to have frequent epizootics of diarrhea in young calves in the last five years, were successfully propagated in cell cultures. The 12 isolates produced clear-cut plaques in BSC-1 cells and, except for one isolate, agglutinated human group ""O"" erythrocytes to an higher titer than bovine erythrocytes. Antisera to each isolate were produced in rabbits and used to study their antigenic relationships. All the isolates shared the group-specific immunofluorescent antigen and were antigenically related as demonstrated by the seroneutralization and hemagglutination-inhibition tests. However, the relationships to the Nebraska rotavirus was quite weak in cases of two Quebec isolates. When the genomes of the various isolates were compared by polyacrylamide gel electrophoresis, at least three different reproducible fractionation patterns could be identified.",,"['Dea, S', 'Archambault, D', 'Elazhary, M A', 'Roy, R S']",,,,
,PMC,Coronavirus minus-strand RNA synthesis and effect of cycloheximide on coronavirus RNA synthesis.,,PMC252730,,,"The temporal sequence of coronavirus plus-strand and minus-strand RNA synthesis was determined in 17CL1 cells infected with the A59 strain of mouse hepatitis virus (MHV). MHV-induced fusion was prevented by keeping the pH of the medium below pH 6.8. This had no effect on the MHV replication cycle, but gave 5- to 10-fold-greater titers of infectious virus and delayed the detachment of cells from the monolayer which permitted viral RNA synthesis to be studied conveniently until at least 10 h postinfection. Seven species of poly(A)-containing viral RNAs were synthesized at early and late times after infection, in nonequal but constant ratios. MHV minus-strand RNA synthesis was first detected at about 3 h after infection and was found exclusively in the viral replicative intermediates and was not detected in 60S single-stranded form in infected cells. Early in the replication cycle, from 45 to 65% of the [3H]uridine pulse-labeled RF core of purified MHV replicative intermediates was in minus-strand RNA. The rate of minus-strand synthesis peaked at 5 to 6 h postinfection and then declined to about 20% of the maximum rate. The addition of cycloheximide before 3 h postinfection prevented viral RNA synthesis, whereas the addition of cycloheximide after viral RNA synthesis had begun resulted in the inhibition of viral RNA synthesis. The synthesis of both genome and subgenomic mRNAs and of viral minus strands required continued protein synthesis, and minus-strand RNA synthesis was three- to fourfold more sensitive to inhibition by cycloheximide than was plus-strand synthesis.",,"['Sawicki, S G', 'Sawicki, D L']",,,,
,PMC,Isolation of a monoclonal antibody that blocks attachment of the major group of human rhinoviruses.,,PMC252692,,,"Reciprocal competition binding assays have previously demonstrated that 20 of 24 human rhinovirus serotypes tested compete for a single cellular receptor. These studies suggested that the vast majority of rhinovirus serotypes utilize a single cellular receptor. With HeLa cells as an immunogen, a mouse monoclonal antibody was isolated which had the precise specificity predicted by the competition binding study. The receptor antibody was shown to protect HeLa cells from infection by 78 of 88 human rhinovirus serotypes assayed. In addition, the receptor antibody protects HeLa cells from infection by three coxsackievirus A serotypes. The receptor antibody was unable to protect cells from infection by a wide range of other RNA and DNA viruses. Using the receptor antibody and human rhinovirus type 15, we determined that the cellular receptor utilized by the vast number of human rhinovirus serotypes is present only on cells of human origin, with the exception of chimpanzee-derived cells. The receptor antibody has a strong affinity for the cellular receptor as evidenced by its rapid binding kinetics and ability to displace previously bound human rhinovirus virions from receptors. No viral variants were identified which could bypass the receptor blockage.",,"['Colonno, R J', 'Callahan, P L', 'Long, W J']",,,,
,PMC,The harderian gland: its tumors and its relevance to humans.,,PMC1298742,,,,,"['Albert, D M', 'Frayer, W C', 'Black, H E', 'Massicotte, S J', 'Sang, D N', 'Soque, J']",,,,
,PMC,Polymicrobial infection in enteritis.,,PMC1418437,,,,,"['Ellis, M E', 'Mandal, B K', 'Brennand, J']",,,,
,PMC,Microneutralization test for respiratory syncytial virus based on an enzyme immunoassay.,,PMC271877,,,"Virus infectivity and antibody neutralization titers for respiratory syncytial virus were determined in cell cultures in microtiter plates. After an appropriate incubation period, the cells were fixed, and an enzyme-linked immunosorbent assay was performed directly in the microtiter plates for detection of virus. Results could be read and recorded automatically, which is especially helpful when running large numbers of tests.",,"['Anderson, L J', 'Hierholzer, J C', 'Bingham, P G', 'Stone, Y O']",,,,
,PMC,Aspects of colibacillosis in farm animals.,,PMC2129572,,,,,"['Wray, C.', 'Morris, J. A.']",,,,
,PMC,Proteolytic cleavage of the E2 glycoprotein of murine coronavirus: host-dependent differences in proteolytic cleavage and cell fusion.,,PMC252664,,,"Cell fusion induced by infection with mouse hepatitis virus strain A59 (MHV-A59) varied markedly in extent and time course in four different murine cell lines. When inoculated at a multiplicity of 3 to 5 PFU per cell, the Sac-, L2, and DBT cell lines began to fuse by 7 h, were fused into confluent syncytia by 9 to 12 h, and peeled from the substrate by 10 to 14 h. These virulent virus-cell interactions were in striking contrast to the moderate interaction of MHV-A59 with the 17 Cl 1 cell line, in which only small syncytia were observed 18 h postinoculation, and greater than 50% of the cells remained unfused by 24 h. The yield of infectious virus produced by 17 Cl 1 cells was 10-fold higher than the yields from the other three cell lines. The processing of the nucleocapsid protein, the membrane glycoprotein E1, and the peplomeric glycoprotein E2 were found to differ significantly in the four cell lines. Since the E2 glycoprotein is responsible for virus-induced cell fusion, we attempted to correlate differences in cellular processing of E2 with differences in fusion of infected cells. The predominant intracellular form of E2 in all cell lines was the 180K species. Pulse-chase experiments showed that a small portion of the 17 Cl 1 cell-associated 180K E2 was cleaved by 1 h after synthesis to yield 90K E2, shown in the preceding paper to consist of two different glycoproteins called 90A and 90B (L. S. Sturman, C. S. Ricard, and K. V. Holmes, J. Virol. 56:904-911, 1985). This cleavage occurred shortly before the release of virions from cells, as shown by pulse-chase experiments. After budding at intracellular membranes, virions released into the medium by the four cell lines contained different ratios of 180K to 90K E2. Virions from Sac- cells, which contained 100% 90K E2, fused L2 cells rapidly without requiring virus replication, whereas virions from 17 Cl 1 cells, which had 50% 90K E2, required trypsin activation to induce rapid fusion (Sturman et al., J. Virol. 56:904-911, 1985). The addition of protease inhibitors to the medium markedly delayed L2 cell fusion induced by MHV infection. The extent of coronavirus-induced cell fusion does not depend solely upon the percent cleavage of the E2 glycoprotein by cellular proteases, since extensive fusion was induced by infection of L2 and DBT cells but not 17 Cl 1 cells, although all three cell lines cleaved E2 to the same extent.(ABSTRACT TRUNCATED AT 400 WORDS)",,"['Frana, M F', 'Behnke, J N', 'Sturman, L S', 'Holmes, K V']",,,,
,PMC,Proteolytic cleavage of the E2 glycoprotein of murine coronavirus: activation of cell-fusing activity of virions by trypsin and separation of two different 90K cleavage fragments.,,PMC252663,,,"In the murine coronavirus mouse hepatitis virus, a single glycoprotein, E2, is required both for attachment to cells and for cell fusion. Cell fusion induced by infection with mouse hepatitis virus strain A59 was inhibited by the addition of monospecific anti-E2 antibody after virus adsorption and penetration. Adsorption of concentrated coronavirions to uninfected cells did not cause cell fusion in the presence of cycloheximide. Thus, cell fusion was induced by E2 on the plasma membrane of infected 17 Cl 1 cells but not by E2 on virions grown in these cells. Trypsin treatment of virions purified from 17 Cl 1 cells quantitatively cleaved 180K E2 to 90K E2 and activated cell-fusing activity of the virions. This proteolytic cleavage yielded two different 90K species which were separable by sodium dodecyl sulfate-hydroxyapatite chromatography. One of the trypsin cleavage products, 90A, was acylated and may be associated with the lipid bilayer. The other, 90B, was not acylated and yielded different peptides than did 90A upon limited digestion with thermolysin or staphylococcal V8 protease. Thus, the cell-fusing activity of a coronavirus required proteolytic cleavage of the E2 glycoprotein, either by the addition of a protease to virions or by cellular proteases acting on E2, which was transported to the plasma membrane during virus maturation. There is a striking functional similarity between the E2 glycoprotein of coronavirus, which is a positive-strand RNA virus, and the hemagglutinin glycoprotein of negative-strand orthomyxoviruses, in that a single glycoprotein has both attachment and protease-activated cell-fusing activities.",,"['Sturman, L S', 'Ricard, C S', 'Holmes, K V']",,,,
,PMC,"Survey of neuraminidase production by Clostridium butyricum, Clostridium beijerinckii, and Clostridium difficile strains from clinical and nonclinical sources.",,PMC268550,,,"Neuraminidase production was investigated in 57 Clostridium butyricum strains, 16 Clostridium beijerinckii strains, and 25 Clostridium difficile strains. Neuraminidase activity was found only in C. butyricum strains originating from one human newborn with neonatal necrotizing enterocolitis, two newborns with hemorrhagic colitis, one infected placenta, and one adult with peritonitis, It was concluded that neuraminidase was not a major virulence factor in C. butyricum strains.",,"['Popoff, M R', 'Dodin, A']",,,,
,PMC,Recombination between nonsegmented RNA genomes of murine coronaviruses.,,PMC252599,,,"We have isolated a recombinant virus between the A59 and JHM strains of mouse hepatitis virus, which contain a single species of nonsegmented RNA genome. This recombinant was derived by mixed infection of DBT cells with temperature-sensitive mutants of A59 and JHM at nonpermissive temperature. Viruses recovered at this temperature were screened by oligonucleotide fingerprinting of their genomic RNAs. One recombinant virus, B1, was found to contain mostly A59-derived sequences, but the 3 kilobases at the 5' end of the genomic RNA was derived from JHM. Thus, the crossover point in the B1 genome is located within gene A, which codes for the viral RNA polymerases. The study of the intracellular RNA species of B1 virus revealed that probably all of the virus-specific subgenomic mRNA species contained the body sequences of strain A59 but the leader sequences of JHM. This result indicates that the JHM leader RNA, which differs from the A59 leader RNA, could be fused to the mRNAs of a different virus strain during RNA transcription. Furthermore, B1 virus-infected cells contain an additional subgenomic mRNA species which is transcribed from a new initiation site within gene C, suggesting that the leader RNA could determine the site of initiation for coronavirus mRNAs. These data represent a first report of RNA recombination between viruses, other than picornaviruses, which contain nonsegmented RNA genomes.",,"['Lai, M M', 'Baric, R S', 'Makino, S', 'Keck, J G', 'Egbert, J', 'Leibowitz, J L', 'Stohlman, S A']",,,,
,PMC,In vivo and in vitro models of demyelinating disease: JHM virus in the rat central nervous system localized by in situ cDNA hybridization and immunofluorescent microscopy.,,PMC252597,,,"In situ probing of central nervous system (CNS) tissues has made it possible to associate the presence of JHM virus (JHMV) RNA with individual cells in the rat CNS. The presence of viral RNA was not always associated with antigen expression. The in situ hybridization revealed that cerebellar Purkinje cells and hippocampal neurons were highly susceptible to JHMV infection during either acute or paralytic disease. In the paralytic disease, Purkinje cell neurons frequently contained viral RNA. This observation suggests that these neurons, and perhaps others, may be repositories for JHMV in rats that undergo prolonged infections.",,"['Sorensen, O', 'Dales, S']",,,,
,PMC,Sugar intolerance complicating acute gastroenteritis.,,PMC1777522,,,"Sugar intolerance occurred in 31 of 200 children admitted to hospital with acute gastroenteritis. In 28 this was transient and settled rapidly, but in the remaining three it indicated a more serious and persistent problem. The most important predisposing factor was viral infection, in particular with rotavirus. The current regimen for the management of sugar intolerance complicating acute gastroenteritis at this hospital is outlined.",,"['Trounce, J Q', 'Walker-Smith, J A']",,,,
,PMC,INFECTION AND IMMUNITY IN FARM ANIMALS,,PMC1236211,,,,,"Clark, E.G.",,,,
,PMC,Cell surface influenza haemagglutinin can mediate infection by other animal viruses.,,PMC554532,,,"We have used filter-grown Madin-Darby canine kidney (MDCK) cells to explore the mechanism by which influenza virus facilitates secondary virus infection. Vesicular stomatitis virus (VSV) and Semliki Forest virus (SFV) infect only through the basolateral surface of these polarized epithelial cells and not through the apical surface. Prior infection with influenza virus rendered the cell susceptible to infection by VSV or SFV through either surface. The presence of both a permissive and a restrictive surface for virus entry in the same cell allowed us to determine how the influenza infection enhanced the subsequent infection of a second virus. Biochemical and morphological evidence showed that influenza haemagglutinin on the apical surface serves as a receptor for the superinfecting virus by binding to its sialic acid-bearing envelope proteins. Influenza virus also facilitates secondary virus infection in non-epithelial cells; baby hamster kidney cells (BHK-21), which are normally resistant to infection by the coronavirus (mouse hepatitis virus MHV-A59), could be infected via the haemagglutinin-sialic acid interaction. Facilitation of secondary virus infection requires only the sialic acid-binding properties of the haemagglutinin since the uncleaved haemagglutinin could also mediate virus entry.",,"['Fuller, S D', 'von Bonsdorff, C H', 'Simons, K']",,,,
,PMC,Serotypes of bovine astrovirus.,,PMC268492,,,"Three isolates of bovine astrovirus, one from the United Kingdom and two from the United States, possessed common antigens by immunofluorescence and strain-specific antigens by neutralization and were designated as two, and probably three, distinct serotypes. The isolate US2, despite being a different serotype, possessed the same restrictive cell tropism and cytopathology as previously reported for isolate US1, of the M cells of the dome epithelium of the Peyer's patches. Serotyping of 16 field isolates indicated the presence of more undefined serotypes.",,"['Woode, G N', 'Gourley, N E', 'Pohlenz, J F', 'Liebler, E M', 'Mathews, S L', 'Hutchinson, M P']",,,,
,PMC,Ultrastructural study of ehrlichial organisms in the large colons of ponies infected with Potomac horse fever.,,PMC261190,,,"Potomac horse fever is characterized by fever, anorexia, leukopenia, profuse watery diarrhea, dehydration, and high mortality. An ultrastructural investigation was made to search for any unusual microorganisms in the digestive system, lymphatic organs, and blood cells of ponies that had developed clinical signs after transfusion with whole blood from horses naturally infected with Potomac horse fever. A consistent finding was the presence of rickettsial organisms in the wall of the intestinal tract of these ponies. The organisms were found mostly in the wall of the large colon, but fewer organisms were found in the small colon, jejunum, and cecum. The organisms were also detected in cultured blood monocytes. In the intestinal wall, many microorganisms were intracytoplasmic in deep glandular epithelial cells and mast cells. Microorganisms were also found in macrophages migrating between glandular epithelial cells in the lamina propria and submucosa. The microorganisms were round, very pleomorphic, and surrounded by a host membrane. They contained fine strands of DNA and ribosomes and were surrounded by double bileaflet membranes. Their ultrastructure was very similar to that of the genus Ehrlichia, a member of the family Rickettsiaceae. The high frequency of detection of the organism in the wall of the intestinal tract, especially in the large colon, indicates the presence of organotrophism in this organism. Infected blood monocytes may be the vehicle for transmission between organs and between animals. The characteristic severe diarrhea may be induced by the organism directly by impairing epithelial cell functions or indirectly by perturbing infected macrophages and mast cells in the intestinal wall or by both.",,"['Rikihisa, Y', 'Perry, B D', 'Cordes, D O']",,,,
,PMC,Role of the thymus in streptococcal cell wall-induced arthritis and hepatic granuloma formation. Comparative studies of pathology and cell wall distribution in athymic and euthymic rats.,,PMC423980,,,"Systemic administration of an aqueous suspension of group A streptococcal cell wall fragments to susceptible rats induces acute and chronic polyarthritis, as well as noncaseating hepatic granulomas. To gain insight into the role of the thymus in the pathogenesis of this experimental model, pathologic responses and cell wall tissue distribution were compared in congenitally athymic rats (rnu/rnu) and their euthymic littermates (NIH/rnu). Within 24 h, both rat strains developed acute arthritis, characterized by polymorphonuclear leukocytic exudate in the synovium and joint spaces. This acute process was maximal at day 3 and gradually subsided. Beginning 2-3 wk after injection, the euthymic, but not the athymic, rats developed the typical exacerbation of arthritis, characterized by synovial cell hyperplasia with villus formation and T helper/inducer lymphocyte-rich mononuclear cell infiltration. This process eventually resulted in marginal erosions and destruction of periarticular bone and cartilage. Parallel development of acute and chronic hepatic lesions was observed. Bacterial cell wall antigen distribution and persistence were similar in the athymic and euthymic rats. Cell wall antigens were demonstrated in the cytoplasm of cells within subchondral bone marrow, synovium, liver, and spleen, coincident with the development of the acute lesions, and persisted in these sites, although in decreasing amounts, for the duration of the experiment. Our findings provide evidence that the acute and chronic phases of the experimental model are mechanistically distinct. The thymus and functional thymus derived-lymphocytes appear not to be required for the development of the acute exudative disease but are essential for the development of chronic proliferative and erosive disease. Induction of disease is dependent upon cell wall dissemination to and persistence in the affected tissues.",,"['Allen, J B', 'Malone, D G', 'Wahl, S M', 'Calandra, G B', 'Wilder, R L']",,,,
,PMC,Competitive enzyme immunoassays for the rapid detection of antibodies to feline infectious peritonitis virus polypeptides.,,PMC268418,,,"Monoclonal antibodies specific for the envelope (E1), peplomer (E2), and nucleocapsid (N) polypeptides of feline infectious peritonitis virus (FIPV) were used in rapid, competitive enzyme-linked immunosorbent assays (ELISA) to study the humoral immune response of cats to FIPV infection. Results from the competitive ELISAs were correlated with those from immunofluorescent antibody assays (IFAs) on 203 samples obtained from 64 individual cats. The IFA results correlated best with those obtained with the anti-E1 specific competitive ELISA (85.7%). In contrast, anti-N and anti-E2 competitive ELISA results correlated with IFA results only 65.5 and 2.4% of the time, respectively. The results of the anti-E1 specific competitive ELISA were not influenced by the total immunoglobulin concentration or the possible presence of free viral antigens in the serum. These results suggest that a competitive ELISA involving the use of enzyme-conjugated monoclonal antibody to the E1 glycoprotein of FIPV is a simple and rapid replacement for the more cumbersome IFA.",,"['Fiscus, S A', 'Teramoto, Y A', 'Mildbrand, M M', 'Knisley, C V', 'Winston, S E', 'Pedersen, N C']",,,,
,PMC,Effect of monensin on the assembly of Uukuniemi virus in the Golgi complex.,,PMC255066,,,"The effect of the carboxylic ionophore monensin on the maturation of Uukuniemi virus, a bunyavirus, and the transport of its two membrane glycoproteins, G1 and G2, were studied in chicken embryo fibroblasts and baby hamster kidney cells. Virus maturation, which occurs in the Golgi complex (E. Kuismanen, K. Hedman, J. Saraste, and R. F. Pettersson, Mol. Cell. Biol. 2:1444-1458, 1982; E. Kuismanen, B. Bång, M. Hurme, and R. F. Pettersson, J. Virol. 51:137-146, 1984), was effectively inhibited by the drug (1 or 10 microM) as studied by electron microscopy and by assaying the release of infectious or radiolabeled virus. Immunoelectron microscopy showed that association of viral nucleocapsids with the cytoplasmic surface of glycoprotein-containing Golgi membranes, a prerequisite for virus budding, was unaffected by monensin. In the presence of the drug, the virus glycoproteins assembled into long, tubular structures extending into the lumen of Golgi-derived vacuoles, suggesting that monensin inhibited a terminal step in the assembly of the virus. Intracellular transport and expression of the virus membrane glycoproteins G1 and G2 at the cell surface were not inhibited by monensin as studied by immunocytochemical and radiolabeling techniques. Pulse-chase experiments in the presence of monensin showed that intracellular G1 acquired only partially endo-H-resistant glycans. The sialylation of G1 appearing on the cell surface in the presence of the drug was decreased, whereas sialylation of G2 apparently was inhibited to a lesser extent, as shown by external labeling of the cells with the periodate-boro[3H]hydride method. Thus, monensin exerted a differential effect on the terminal glycosylation of G1 and G2. Unlike several membrane and secretory glycoproteins, both G1 and G2 could enter a functional transport pathway in the presence of monensin and become expressed at the cell surface.",,"['Kuismanen, E', 'Saraste, J', 'Pettersson, R F']",,,,
,PMC,Experimental reproduction of Potomac horse fever in horses with a newly isolated Ehrlichia organism.,,PMC268372,,,"Potomac horse fever, a recently recognized disease of equines, characterized by high fever, leukopenia, and a profuse diarrhea, was studied for its etiology. An Ehrlichia organism was isolated in equine macrophage-fibroblast cell cultures and mouse macrophage cell cultures from the mononuclear cells of blood of infected horses. The agent was continuously propagated in mouse macrophage cell cultures. The organism multiplied in the cytoplasm of mouse macrophage cells and was identified by Giemsa staining, acridine orange staining, and by indirect immunofluorescence with convalescent sera from infected horses. The disease was experimentally reproduced in horses inoculated with Ehrlichia-infected cell culture material. The Ehrlichia organism was reisolated from the blood of these infected horses during the course of the disease. Antibody against the organism was detected in the sera of experimentally infected horses. This study confirmed that the new Ehrlichia organism is the etiological agent of Potomac horse fever.",,"['Dutta, S K', 'Myrup, A C', 'Rice, R M', 'Robl, M G', 'Hammond, R C']",,,,
,PMC,Effect of specific humoral immunity and some non-specific factors on resistance of volunteers to respiratory coronavirus infection.,,PMC2129501,,,"Thirty-three volunteers were inoculated intranasally with coronavirus 229 E, and their responses monitored by antibody rises, symptomatology and virus excretion. These were related to their pre-trial immune status as indicated by concentrations of specific antibodies and non-specific proteins in serum and nasal washings. Both circulating and local specific antibodies were associated with protection from infection and disease, but only specific IgA antibodies of either type appeared to shorten the period of virus shedding. Although total secretory IgA was significantly associated only with reduction of symptoms, total protein in nasal washings appeared to protect against infection also, indicating that other locally produced proteins, not identified, may be associated with resistance. Two of the many factors which may affect the concentration of circulating and local protective proteins and thus influence the outcome of virus inoculation, namely, sex of the volunteer and the interval since the previous cold, were examined. Male volunteers or volunteers who had had evidence of a recent respiratory infection were less likely to be infected, but if they were infected, they had lower clinical scores and stopped shedding virus earlier than the rest. These groups possessed higher concentrations of specific antibodies and non-specific proteins in their pre-challenge sera and/or nasal washings. The significance of these findings is discussed.",,"Callow, K. A.",,,,
,PMC,Parvovirus-like particles associated with diarrhea in unweaned piglets.,,PMC1236185,,,"Numerous parvovirus-like particles, 18 to 26 nm in diameter, were detected by electron microscopy in the intestinal contents of two to three week old piglets with mild to severe diarrhea, in six Quebec pig herds. Hemagglutination of guinea pig and African green monkey red blood cells was obtained with clarified intestinal contents. Two isolates were found to be antigenically related to porcine and canine parvoviruses, while another differed from the porcine parvovirus using the hemagglutination-inhibition test. Three isolates could be cultivated in cell cultures as demonstrated by the development of a cytopathic effect, hemagglutination activity, immunofluorescence and identification of the virions in the cell culture fluids by electron microscopy. The possibility of a primary etiological role for these parvoviruses in diarrhea of unweaned piglets is discussed.",,"['Dea, S', 'Elazhary, M A', 'Martineau, G P', 'Vaillancourt, J']",,,,
,PMC,Experimental inoculation of cats with human coronavirus 229E and subsequent challenge with feline infectious peritonitis virus.,,PMC1236175,,,"Minimal-disease cats exposed to live human coronavirus 229E developed homologous antibody responses that suggested little or no replication of the virus in inoculated animals. Oronasal and subcutaneous inoculation of coronavirus 229E did not elicit an antibody response by heterologous (transmissible gastroenteritis virus, canine coronavirus) neutralization or by heterologous (transmissible gastroenteritis virus) kinetics-based enzyme-linked immunosorbent assay. No clinical signs attributable to coronavirus 229E were seen in inoculated cats. Although the number of animals in each of the five experimental groups was small (n = 2), antibodies produced in response to the virus did not appear to sensitize cats to subsequent feline infectious peritonitis virus challenge, but neither did they cross-protect cats against the challenge dose.",,"['Barlough, J E', 'Johnson-Lussenburg, C M', 'Stoddart, C A', 'Jacobson, R H', 'Scott, F W']",,,,
,PMC,Diagnosis of TGE Virus Infection in Swine Herds,,PMC1680090,,,,,"['Bauck, S.', 'Stone, M.W.']",,,,
,PMC,Influences of nutrition on immunity and susceptibility to mouse hepatitis virus type 2.,,PMC1453636,,,"Resistance to mouse hepatitis virus (MHV) in C3H mice is a genetic trait which appears 3-4 weeks after birth. However, when these animals were weaned on a low protein diet (8% casein), they remained susceptible to MHV-2 infection until they reached 8-9 weeks of age. During this period, the protein-restricted C3H mice were as susceptible to MHV-2 as the genetically susceptible congenic C3Hss strain. The delay in the emergence of resistance in the protein-restricted mice could be corrected by injecting these animals with spleen cells from 6-week-old C3H mice. Thymocytes from normal C3H mice, and splenocytes and thymocytes from protein-restricted C3H mice, were not protective. However, spleen cells from the protein-restricted mice were more responsive to phytohaemagglutinin, lipopolysaccharide and concanavalin A than spleen cells from normal C3H. The enhanced lymphoproliferative response in spleen cells from protein-restricted mice was abrogated by the addition of plastic-adherent cells obtained from normal C3H spleens. Spleen cells from protein-restricted and from genetically susceptible C3Hss mice also possessed more spontaneous cytotoxicity against MHV-infected 3T3 fibroblasts.",,"['Esa, A H', 'Reissig, M']",,,,
,PMC,Triggering infections in reactive arthritis.,,PMC1001660,,,"Certain microbes like yersinia, salmonella, shigella, campylobacter, chlamydia, and possibly gonococcus can trigger reactive arthritis especially in patients of the HLA-B27 type. In the present study we have used serological and culture methods to identify the probable triggering infection in 50 consecutive HLA-B27 positive patients diagnosed as having reactive arthritis. The two most common triggering agents thus identified were Yersinia enterocolitica (12 patients) and Chlamydia trachomatis (11 patients). In addition six patients had high antistreptolysin O titres and two high teichoic acid antibody titres suggesting group A streptococci and Staphylococcus aureus as triggering agents. In 13 patients no preceding infection could be identified. The identity of the infective agent seems to have very little effect on the clinical picture of the reactive arthritis - the only difference between the various aetiological groups in the present material was absence of fever in the patients with a preceding C. trachomatis infection, of whom only one out of 11 had a temperature greater than or equal to 38 degrees C, whereas 13 of 16 patients with a preceding enterobacterial, and five of the eight patients with a streptococcal or staphylococcal infection had raised temperatures.",,"['Valtonen, V V', 'Leirisalo, M', 'Pentikäinen, P J', 'Räsänen, T', 'Seppälä, I', 'Larinkari, U', 'Ranki, M', 'Koskimies, S', 'Malkamäki, M', 'Mäkelä, P H']",,,,
,PMC,"In vitro activity of WIN 51711, a new broad-spectrum antipicornavirus drug.",,PMC180179,,,"WIN 51711 (5-[7-[4-(4,5-dihydro-2-oxazolyl)phenoxy]heptyl]-3-methylisoxazole), a new antipicornavirus drug, is a potent inhibitor of human entero- and rhinoviruses at concentrations not inhibitory to HeLa cell growth. In plaque reduction assays, WIN 51711 reduced plaque formation by 9 enteroviruses and 33 rhinoviruses, with MICs of 0.004 to 0.17 and 0.004 to 6.2 micrograms/ml, respectively. Addition of WIN 51711 to infected cells at concentrations of 0.02 to 5.0 micrograms/ml reduced the yield of picornaviruses by 90%. Other RNA viruses (nonpicornaviruses) and DNA viruses were unaffected by the compound.",,"['Otto, M J', 'Fox, M P', 'Fancher, M J', 'Kuhrt, M F', 'Diana, G D', 'McKinlay, M A']",,,,
,PMC,An avirulent G1 glycoprotein variant of La Crosse bunyavirus with defective fusion function.,,PMC254862,,,"La Crosse virus, a member of the California serogroup of the family Bunyaviridae, causes encephalitis in humans and laboratory rodents. A variant virus (V22) selected with a monoclonal antibody against the large (G1) glycoprotein showed diminished neuroinvasiveness after peripheral inoculation. This variant has an alteration in its fusion function, requiring a lower pH for the activation of fusion and demonstrating reduced efficiency of cell-to-cell fusion of BHK-21 cultures. V22 was studied in detail following the infection by intraperitoneal or intracerebral routes in suckling, weanling, or adult CD-1 mice. It exhibited a marked reduction in its ability to replicate in striated muscle and to produce viremia; however, after intracerebral injection V22 virus replicated almost as rapidly in brain as its parent, La Crosse virus. V22 virus thus represents an example of reduced neuroinvasiveness associated with an alteration at a specific epitope of the G1 glycoprotein. This same epitope also influences the fusion activity of the glycoprotein.",,"['Gonzalez-Scarano, F', 'Janssen, R S', 'Najjar, J A', 'Pobjecky, N', 'Nathanson, N']",,,,
,PMC,Nucleotide sequence of the G protein gene of human respiratory syncytial virus reveals an unusual type of viral membrane protein.,,PMC397937,,,"The major surface glycoprotein (G) of human respiratory syncytial (RS) virus has an estimated mature Mr of 84,000-90,000. Among a library of cDNA clones prepared from RS virus mRNAs, we identified clones that hybridized to a message that encoded a Mr 36,000 polypeptide that was specifically immunoprecipitated with anti-G antiserum. The amino acid sequence of the G protein backbone was determined by nucleotide sequence analysis of several of the cDNA clones. It contains a combination of structural features that make it unique among the known viral glycoproteins. The G mRNA is 918 nucleotides long and contains a single major open reading frame that encodes a polypeptide having 298 amino acid residues with a Mr of 32,587, a finding consistent with the Mr 36,000 estimate for the in vitro translation product of the G mRNA. This suggests that greater than 50% of the molecular weight of the mature glycoprotein may be contributed by carbohydrate. Glycosylation of G is largely resistant to tunicamycin, an inhibitor of the attachment of N-linked oligosaccharides, suggesting that the majority of the carbohydrate residues are attached via O-glycosidic bonds. In accordance with this, serine and threonine residues, the acceptor sites for O-linked oligosaccharides, comprise 30.6% of the total amino acid composition. There are also four potential acceptor sites for N-linked oligosaccharides. The amino acid sequence lacks both an NH2-terminal hydrophobic signal sequence and a COOH-terminal hydrophobic region. Instead, a strongly hydrophobic region is located between amino acid residues 38 and 66. This region may serve as both the signal to insert the nascent polypeptide through the membrane and as the membrane anchor site.",,"['Wertz, G W', 'Collins, P L', 'Huang, Y', 'Gruber, C', 'Levine, S', 'Ball, L A']",,,,
,PMC,"United Kingdom scheme for external quality assessment in virology. Part II. Specimen distribution, performance assessment, and analyses of participants' methods in detection of rubella antibody, hepatitis B markers, general virus serology, virus identification, and electron microscopy.",,PMC499205,,,"Methods for the preparation and pre-distribution testing of specimens for external quality assessment in virology have been defined and criteria for allocation of scores for participants' reports on each category of specimen have been established. Specimens for detection of rubella antibody or markers of hepatitis B infection consist of human serum samples, which are distributed after detailed assessment of the expected results. In testing for rubella antibody or hepatitis B surface antigen (HBsAg) the scores given for reports of positive, equivocal, or negative depend on the specimen's content of antibody or HBsAg as established in the external quality assessment laboratory. For general virus serology two serum samples must be tested against a designated antigen by the complement fixation method; the score allocated for each participant's results depends on the ratio of the two titres he records, which is then compared with a target value derived from the results of a panel of participating laboratories. In virus identification and electron microscopy specimens are prepared from cultures or from clinical samples, and scores depend on the accuracy of identification. The pre-distribution tests necessary to establish the virus content and stability of these specimens have been defined, and media suitable for transporting specimens for virus culture, fluorescent antibody staining, or electron microscopy have been developed. A participant's overall success rate for each specimen is judged from the mean score (maximum 2) calculated from the scores of all participants examining the specimen. Mean scores were highest for detection of rubella antibody or HBsAg (from 1.67 to 1.96) and lowest for specimens containing certain small enteric viruses distributed for electron microscopy (0.82 to 1.12). Participants' reports on the methods used for each specimen have been analysed. Current changes and developments in methods have been recorded, and attempts have been made to relate the use of various techniques and test kits to successes or failures with various types of specimen.",,"['Reed, S E', 'Gardner, P S', 'Stanton, J']",,,,
,PMC,Characterization of a variant virus selected in rat brains after infection by coronavirus mouse hepatitis virus JHM.,,PMC254814,,,"The intracerebral inoculation of Lewis rats with the murine coronavirus MHV-JHM leads in the majority of animals to acute encephalitis and death within 14 days. Viral RNAs isolated from the brains of animals 5 to 7 days after infection were compared by Northern blot analysis with the RNAs produced during the lytic infection of Sac(-) or DBT cells with wild-type MHV-JHM (wt virus). Reproducibly, the subgenomic mRNAs 2 and 3 but no other viral RNAs were significantly larger in the brain-derived material. All viruses isolated from infected brain material displayed and maintained this altered mRNA profile when cultivated in Sac(-) or DBT cells. A virus isolated from the infected brain material, MHV-JHM clone 2 (cl-2 virus), has been further characterized. This isolate grew in tissue culture and induced cytopathic effects comparable to those induced by wt virus. However, the mRNAs 2 and 3 produced in cl-2 virus-infected cells had molecular weights ca. 150,000 larger than those produced in cells infected with wt virus. There was no detectable difference in genome-sized RNA (mRNA 1) or subgenomic mRNAs 4, 5, 6, and 7 as determined by electrophoresis in agarose gels. T1-resistant oligonucleotide analysis of genomic RNA revealed one additional and one missing oligonucleotide in the fingerprint of cl-2 virus compared with wt virus. The oligonucleotide fingerprints of intracellular mRNA 3 were identical for both viruses. Pulse-labeling with [35S]methionine in the presence of tunicamycin showed that the primary translation product of mRNA 3, the E2 apoprotein, was ca. 15,000 larger in molecular weight in cl-2 virus-infected cells. These data show that viruses with larger mRNAs 2 and 3 (the latter encoding an altered E2 glycoprotein) are selected for multiplication in rat brains. Mechanisms for the generation of such variants and the possible nature of their selective advantage are considered.",,"['Taguchi, F', 'Siddell, S G', 'Wege, H', 'ter Meulen, V']",,,,
,PMC,Structure of the intracellular defective viral RNAs of defective interfering particles of mouse hepatitis virus.,,PMC254801,,,"The intracellular defective RNAs generated during high-multiplicity serial passages of mouse hepatitis virus JHM strain on DBT cells were examined. Seven novel species of single-stranded polyadenylic acid-containing defective RNAs were identified from passages 3 through 22. The largest of these RNAs, DIssA (molecular weight [mw], 5.2 X 10(6)), is identical to the genomic RNA packaged in the defective interfering particles produced from these cells. Other RNA species, DIssB1 (mw, 1.9 X 10(6) to 1.6 X 10(6)), DIssB2 (mw, 1.6 X 10(6)), DIssC (mw, 2.8 X 10(6)) DIssD (mw, 0.82 X 10(6)), DIssE (mw, 0.78 X 10(6)), and DIssF (mw, 1.3 X 10(6)) were detected at different passage levels. RNase T1-resistant oligonucleotide fingerprinting demonstrated that all these RNAs were related and had multiple deletions of the genomic sequences. They contained different subsets of the genomic sequences from those of the standard intracellular mRNAs of nondefective mouse hepatitis virus JHM strain. Thus these novel intracellular viral RNAs were identified as defective interfering RNAs of mouse hepatitis virus JHM strain. The synthesis of six of the seven normal mRNA species specific to mouse hepatitis virus JHM strain was completely inhibited when cells were infected with viruses of late-passage levels. However, the synthesis of RNA7 and its product, viral nucleoprotein, was not significantly altered in late passages. The possible mechanism for the generation of defective interfering RNAs was discussed.",,"['Makino, S', 'Fujioka, N', 'Fujiwara, K']",,,,
,PMC,Acute otitis media: a new treatment strategy.,,PMC1418336,,,"The incidence of acute otitis media and its response to treatment only with nose drops and analgesics (but without antibiotics or myringotomy) were assessed over three months by 45 doctors in and around Tilburg. In addition, over 17 months 60 general practitioners assessed the effects of this limited treatment in children aged 2 to 12 years and referred all those in whom the condition took an unsatisfactory course (either a severe course--illness continuing beyond three to four days with high temperature or pain, or both--or persistent discharge after 14 days) to an ear, nose, and throat specialist. Those referred because of appreciable illness continuing beyond three or four days were entered into a further study, comparing the effects of myringotomy alone, antibiotics alone, and myringotomy and antibiotics combined. Bacteriology was assessed in all children in whom the course of the condition was unsatisfactory. More than 90% of an estimated 4860 children seen over 17 months (estimation based on incidence of severe course in the three month study) recovered within a few days. The course of the condition was severe in only 126 (2.7%) patients; haemolytic streptococci group A were identified in 30 of these 126 patients but Haemophilus influenzae in only one. One hundred of these patients with a severe course entered the trial of treatment, which showed antimicrobial treatment either alone or in combination to be more effective than myringotomy alone. Whether combined treatment was more effective than antibiotics alone remained unconfirmed. Acute otitis media in children can be treated with nose drops and analgesics alone for the first three to four days. Patients in whom this regimen is not accompanied by satisfactory recovery can be recognised within a short time and treated by the general practitioner.",,"['van Buchem, F L', 'Peeters, M F', ""van 't Hof, M A""]",,,,
,PMC,Clinicopathologic responses in cats with feline leukemia virus-associated leukemia-lymphoma treated with staphylococcal protein A.,,PMC1887935,,,"Purified protein A from Staphylococcus aureus Cowan I was injected intraperitoneally or was incorporated in filters ex vivo through which plasma from cats with feline leukemia virus (FeLV)-associated leukemia-lymphoma was passed. Before treatment, 65% of the FeLV-infected cats were anemic, and 70% were thrombocytopenic. Concomitant infections, or immune-mediated disease, was common. During treatment 50% of the cats with FeLV-associated disease improved objectively with normal posttreatment hematocrits, thrombocyte and leukocyte counts, disappearance of dysplastic hematologic elements, and correction of marrow dyscrasias. A 33% response to treatment occurred in cats with unequivocal manifestations of malignant disease and was characterized by reductions in tumor size and marrow and peripheral blood neoplastic cell populations. Clearance of FeLV viremia was documented in 28% of the treated cats. The several possible mechanisms by which treatment with staphylococcal protein A causes reduction in the extent of malignant disease are considered.",,"['Engelman, R. W.', 'Tyler, R. D.', 'Trang, L. Q.', 'Liu, W. T.', 'Good, R. A.', 'Day, N. K.']",,,,
,PMC,An Outbreak of Diarrhea in Piglets Caused by a Coronavirus Antigenically Distinct from Transmissible Gastroenteritis Virus,,PMC1679994,,,Coronavirus-like particles were visualized by electron microscopy in the intestinal contents of piglets during a diarrheal outbreak on a Quebec pig farm. The precipitating antigens of transmissible gastroenteritis virus were not detected in the intestinal contents of diarrheic animals by counter-immunoelectrophoresis. Insignificant antibody titers against transmissible gastroenteritis virus were demonstrated in the sera of convalescent pigs by indirect immunofluorescence and these sera did not react with transmissible gastroenteritis virus when tested by immunoelectron microscopy. The causative agent could not be isolated in cell cultures. It was concluded that a coronavirus antigenically distinct from transmissible gastroenteritis virus was responsible for the enteric problems observed on this farm. The outbreak was controlled after oral inoculation of adult pigs with infected intestinal contents.,,"['Dea, S.', 'Vaillancourt, J.', 'Elazhary, Y.', 'Martineau, G. P.']",,,,
,PMC,Experimental cecitis in gnotoxenic chickens monoassociated with Clostridium butyricum strains isolated from patients with neonatal necrotizing enterocolitis.,,PMC261361,,,"An animal model for Clostridium butyricum necrotizing cecitis has been developed in axenic chickens inoculated orally between 2 and 50 days of life. Cecitis was obtained with two C. butyricum strains isolated from neonatal necrotizing enterocolitis and not with a Clostridium beijerinckii strain from dairy products; the rate of colonization of the intestinal tract by this strain was lower than that obtained with C. butyricum strains. The clinical findings showed a slow gain in body weight. The cecitis lesions were well developed 3 and 4 weeks after oral inoculation, including enlargement with an increase of the cecum weight-body weight ratio, a marked hyperplasia, congestion, inflammatory infiltrate and pneumatosis of the cecal wall and mesentery, hemorrhage in the lamina propria and submucosa, and ulcerations and necrotic areas in the mucosa. By immunofluorescence and electron microscopy, the bacterial cells were located in the cecal lumen and in necrotic areas of the mucosa. The presence of 4% lactose in the diet seemed to be a prerequisite for the development of cecitis in chickens. A gradual rise of fluorescent antibodies in the sera was observed.",,"['Popoff, M R', 'Szylit, O', 'Ravisse, P', 'Dabard, J', 'Ohayon, H']",,,,
,PMC,Differential susceptibility of cultured neural cells to the human coronavirus OC43.,,PMC254747,,,"By using cell-type-specific markers and neural cultures derived from various areas of the nervous system, it has been possible to identify various interactions between OC43 virus and mouse oligodendrocytes, neurons, astrocytes, and fibroblasts. Neurons derived from dorsal root ganglia produced viral antigen and infectious virus. Astrocytes and fibroblasts both produced viral antigen but not infectious virus. Oligodendrocytes produced neither infectious virus nor viral antigen. Human embryo brain cells, including astrocytes, were susceptible to OC43 infection but did not produce infectious virus.",,"['Pearson, J', 'Mims, C A']",,,,
,PMC,Three intergenic regions of coronavirus mouse hepatitis virus strain A59 genome RNA contain a common nucleotide sequence that is homologous to the 3' end of the viral mRNA leader sequence.,,PMC254715,,,"cDNA clones that represent various portions of the coronavirus mouse hepatitis virus strain A59 genome RNA have been constructed. cDNAs were synthesized by transcription of genome RNA by using either oligo(dT) or random oligomers of calf thymus DNA as primers. These cDNAs were converted into double-stranded DNA and cloned into pBR322 by standard techniques. The resulting cloned viral DNA fragments were mapped to viral genes by hybridization with Northern blots of intracellular RNA from mouse hepatitis virus strain A59-infected cells. These cDNA clones map in six of the seven viral genes. Clone g344, 1.8 kilobases, is the largest and encompasses gene 5 (which encodes a nonstructural protein) and gene 6 (which encodes the E1 viral glycoprotein) as well as the intergenic regions preceding genes 5, 6, and 7. Sequencing of parts of this cloned DNA show that these three intergenic regions contain a common 11-nucleotide sequence. This sequence shares homology with the 3' end of the viral mRNA leader sequence. Thus, this common intergenic sequence may contain a binding site for a leader RNA that hybridizes to negative-strand viral RNA at the beginning of each gene to prime mRNA synthesis. The different degrees of homology between the leader and its putative binding site may influence the differential rates of transcription of the various viral mRNAs.",,"['Budzilowicz, C J', 'Wilczynski, S P', 'Weiss, S R']",,,,
,PMC,"Experimental Allergic Encephalomyelitis: A Useful Model for Multiple Sclerosis: Progress in Clinical and Biological Research, vol 146",,PMC1289610,,,,,"Hughes, Richard A C",,,,
,PMC,Virus infections in immunocompromised patients: their importance and their management.,,PMC1289576,,,"Opportunistic viral infections were investigated in 156 adult patients admitted over one year to a medical oncology service: 35% of the total group and 65% of those with acute leukaemia experienced viral infections, 79% of which were with viruses of the herpes group. Surprisingly few enteric viruses were recovered. Reactivation of herpes simplex virus in the brains of these immunosuppressed patients was suggested by the demonstration by nucleic acid hybridization of herpes simplex virus DNA sequences in neurones and endothelial cells in patients with evidence of past infection with virus. Acyclovir was effective in therapy and prophylaxis. Twenty-three strains from 7 patients were tested for sensitivity to this antiviral: in 3 instances clinical resistance was observed but the strains were fully sensitive in vitro, as were all other strains tested.",,"['Sutton, R N', 'Itzhaki, R F', 'Christophers, J', 'Saldanha, J', 'Gannicliffe, A', 'Anderson, H']",,,,
,PMC,Reovirus serotype 1 intestinal infection: a novel replicative cycle with ileal disease.,,PMC254649,,,"After oral inoculation, reovirus serotype 1 strain Lang was shown to specifically infect the epithelial cells of the ileum, while sparing the epithelial cells in the duodenum, jejunum, and colon. The initial site of replication was localized in cells of the crypts of Lieberkühn adjacent to Peyer's patches. Virus was subsequently found by immunoperoxidase staining in cells migrating up the crypt-villus complex throughout the ileum. The severity of the pathological changes in the ileum was proportional to the concentration of the viral inoculum. This site-specific infection of the ileum by reovirus may provide a model for diseases that are restricted to specific sites in the intestine.",,"['Rubin, D H', 'Kornstein, M J', 'Anderson, A O']",,,,
,PMC,The use of the single radial haemolysis technique in the serological diagnosis of dengue and Japanese encephalitis virus infections,,PMC2536462,,,"The single radial haemolysis test for the serological diagnosis of suspected dengue and Japanese encephalitis virus infections uses crude virus antigens with a haemagglutinin titre of 1:320 or 1:640. The results, which may be read 3 hours after the addition of a patient's serum, showed a general agreement between this test and haemagglutination-inhibition tests in the number of case diagnoses that were confirmed. The antibody responses of individual patients shown by the two tests, however, were different, which suggests that the two tests may not be measuring the same antibody. The single radial haemolysis test can distinguish between dengue and Japanese encephalitis viruses using specific mouse hyperimmune sera. Tests on a limited number of sera from Japanese encephalitis patients also showed no cross-reactions with dengue virus antigens in those cases having a low-titred but significant fourfold antibody rise to Japanese encephalitis antigen.",,"['Chan, Y. C.', 'Tan, H. C.', 'Tan, S. H.', 'Balachandran, K.']",,,,
,PMC,Recombinant vaccinia viruses as live virus vectors for vaccine antigens: Memorandum from a WHO/USPHS/NIBSC Meeting,,PMC2536414,,,"A scientific workshop sponsored by the World Health Organization, the US Public Health Service, and the National Institute for Biological Standards and Control, London, was held in Bethesda, MD, USA, on 13 and 14 November 1984 to review progress in research relevant to the development of genetically and antigenically modified vaccinia viruses as live vaccines for human and veterinary use. The meeting was followed by an informal consultation convened by WHO to consider the advantages and disadvantages of this approach to vaccine design and production. The needs for further research and the potential role of WHO in coordinating and encouraging international activities in this area were discussed. This report summarizes the proceedings of the scientific workshop and the recommendations made by the WHO consultation.",,,,,,
,PMC,Des formes recombinantes du virus de la vaccine utilisées comme vecteurs viraux vivants pour des antigènes vaccinaux: Mémorandum d'une Réunion OMS/USPHS/NIBSC,,PMC2536375,,,,,,,,,
,PMC,"Progress in enzyme immunoassays: production of reagents, experimental design, and interpretation",,PMC2536367,,,"Enzyme immunoassays represent in many cases the preferred procedure for the detection of antigens or corresponding antibodies. However, many of the current procedures are performed suboptimally. This article reviews the available designs, auxiliary recognition systems, production and purification of antibodies, conjugation procedures, solid-phase materials, recording and interpretation of results, and quality control and standardization of procedures to improve the reproducibility of tests.",,"Kurstak, Edouard",,,,
,PMC,A field trial to evaluate the efficacy of a combined rotavirus-coronavirus/Escherichia coli vaccine in dairy cattle.,,PMC1236108,,,"A field trial was designed to determine the efficacy of a combination rotavirus-coronavirus/Escherichia coli vaccine on dairy farms in southwestern Ontario. In Part A of the trial, 321 cows on 15 farms were randomly assigned to either vaccination or placebo groups. On eight farms, 50% of the dams were vaccinated, while on the other seven farms, 80% of the dams were vaccinated. In Part B of the trial, 26 farms were randomly assigned to either a total vaccination program or to no vaccination program. Mortality, disease occurrence and weight gains were recorded on all calves for the first two weeks of life. In Part A, 23.5% of all calves were treated in the first two weeks of life, 20.9% were treated specifically for scours and 3.6% of live-born calves died. Enteropathogenic E. coli was identified on 13 of the 15 farms, rotavirus on 11 and coronavirus on ten. At least one of the three potential pathogens was found on every farm. There were no significant differences between calves from placebo-treated and vaccine-treated dams with regard to the proportion treated for all diseases, or for scours, or the proportion which died. Neither were there differences in days to first treatment for all diseases (seven days on average), days to first scour (6.7 days), duration of treatments (3.9 days for all diseases, 3.7 days for scours), or estimated weight gains (0.5 kg/day to 14 days). These results were not altered when the presence or absence of enteropathogenic E. coli, rotavirus or coronavirus on the premises was accounted for.(ABSTRACT TRUNCATED AT 250 WORDS)",,"['Waltner-Toews, D', 'Martin, S W', 'Meek, A H', 'McMillan, I', 'Crouch, C F']",,,,
,PMC,Anatomy of the herpes simplex virus 1 strain F glycoprotein B gene: primary sequence and predicted protein structure of the wild type and of monoclonal antibody-resistant mutants.,,PMC255021,,,"In this paper we report the nucleotide sequence and predicted amino acid sequence of glycoprotein B of herpes simplex virus 1 strain F and the amino acid substitutions in the domains of the glycoprotein B gene of three mutants selected for resistance to monoclonal antibody H126-5 or H233 but not to both. Analyses of the amino acid sequence with respect to hydropathicity and secondary structure yielded a two-dimensional model of the protein. The model predicts an N-terminal, 29-amino-acid cleavable signal sequence, a 696-amino-acid hydrophilic surface domain containing six potential sites for N-linked glycosylation, a 69-amino-acid hydrophobic domain containing three segments traversing the membrane, and a charged 109-amino-acid domain projecting into the cytoplasm and previously shown to marker rescue glycoprotein B syn mutations. The nucleotide sequence of the mutant glycoprotein B DNA fragments previously shown to marker transfer or rescue the mutations revealed that the amino acid substitutions cluster in the hydrophilic surface domain between amino acids 273 and 305. Analyses of the secondary structure of these regions, coupled with the experimentally derived observation that the H126-5- and H233-antibody cognitive sites do not overlap, indicate the approximate locations of the epitopes of these neutralizing, surface-reacting, and immune-precipitating monoclonal antibodies. The predicted perturbations in the secondary structure introduced by the amino acid substitutions correlate with the extent of loss of reactivity with monoclonal antibodies in various immunoassays.",,"['Pellett, P E', 'Kousoulas, K G', 'Pereira, L', 'Roizman, B']",,,,
,PMC,The Jeremiah Metzger lecture. Climatology and the common cold.,,PMC2279651,,,,,"Gwaltney, J. M.",,,,
,PMC,Who should be immunised against hepatitis B?,,PMC1443502,,,,,"Zuckerman, A J",,,,
,PMC,Medicine and Books,,PMC1443201,,,,,,,,,
,PMC,Central serous chorioretinopathy: a seasonal variation?,,PMC1040453,,,"A review of 345 consecutive cases of patients under the age of 40 years with central serous chorioretinopathy seen between 1969 and 1979 was performed in order to define temporal patterns of occurrence. The monthly distribution of cases significantly differed (p less than 0.01) from an expected random distribution. Although a statistical trend analysis failed to confirm a definite seasonal variation (p less than 0.01), an increased number of cases were seen in March and April.",,"['Cassel, G. H.', 'Brown, G. C.', 'Annesley, W. H.']",,,,
,PMC,Metabolic Acidosis Without Clinical Signs of Dehydration in Young Calves,,PMC1790659,,,"Metabolic acidosis without clinical signs of dehydration was diagnosed in four calves between nine and 21 days of age. In each calf either coma or depression with weakness and ataxia was observed. Two calves had slow deep respirations. Treatment with intravenous administration of solutions of sodium bicarbonate was accompanied by a rise in blood pH and a return to normal demeanor, ambulation and appetites, allowing these calves to return to their respective herds.",,"['Kasari, T. R.', 'Naylor, J. M.']",,,,
,PMC,Bluetongue virus type 17 can exist in a latent state in MDBK cells.,,PMC254518,,,"An infection with bluetongue virus type 17 can be regulated by the temperature of incubation to be either persistent, producing low levels of virus; lytic, producing a high titer of released virus; or latent, producing no detectable virus. The persistent and latent states are reversible.",,"['Hallum, J V', 'DeWan, P C', 'Boone, M A']",,,,
,PMC,Infectious diarrhea of infant rats produced by a rotavirus-like agent.,,PMC254494,,,"During the investigation of an outbreak of diarrhea in suckling rats, a virus morphologically identical to but antigenically distinct from rotaviruses was identified. The disease was characterized clinically by erythema and cracking and bleeding of the perianal skin associated with the excretion of poorly formed fecal pellets, liquid, and gas. Light microscopy-observable changes consisted of small intestinal villous atrophy, villous epithelial necrosis, and villous epithelial syncytial cell formation. The cytoplasm of the epithelial syncytial cells contained large numbers of 80-nm viral particles that were often associated with reticular aggregates of electron-dense material. Viral infection principally involved the luminal one-fourth to one-third of the intestinal villi as determined by indirect immunofluorescence. This rotavirus-like agent contained 11 double-stranded RNA segments; however, the migration pattern of these segments in polyacrylamide gels differed from the electrophoretic pattern which is characteristic of the typical rotaviruses. The agent had a buoyant density in CsCl of 1.36 to 1.4 g/cm3 and was labile at pH 3 and at 56 degrees C; however, infectivity of viral inocula was not altered by extensive treatment with ether or by pH 5 buffers. This disease, which we have named infectious diarrhea of infant rats, is the first recognized viral diarrhea of rats and appears to be a good model for the study of the recently recognized group of atypical rotaviruses.",,"['Vonderfecht, S L', 'Huber, A C', 'Eiden, J', 'Mader, L C', 'Yolken, R H']",,,,
,PMC,Micro-organisms in gastroenteritis.,,PMC1628695,,,"We present bacteriological and virological findings together with salient clinical features from a prospective study of 447 children aged under 2 years admitted to hospital with infectious gastroenteritis. Putative pathogenic micro-organisms were identified in the stools of 75% of these children. Eight identifiably distinct groups of viruses, found on electron microscopy and tissue culture were present in 67% of patients--rotavirus was detected most frequently. Pathogenic bacteria (salmonellas, shigellas, Escherichia coli, and Campylobacter jejuni--but excluding Clostridium difficile) were found in 16% only. Altogether 4 X 9% of 390 patients had gastroenteritis associated with Cl difficile toxin. The mean duration of diarrhoea was shortest in patients with identifiable virus, with rotavirus having a mean of 5 X 01 days, and was longest in patients with pathogenic bacteria in the stools (11 X 14 days). The finding of more than one type of virus did not seem to be associated with a significantly increased duration of diarrhoea. There are few clinical features which can be associated specifically with any particular micro-organism or groups of these. Multiple organism isolation was common, but the severity of the illness in those patients with at least two types of organism was not greater. Certain viruses, including the norwalk-like virus, known to be associated with outbreaks of gastroenteritis were found as frequently in a group of patients who did not have diarrhoea studied for comparison. Virus was still detectable in the stools of up to 40% of asymptomatic children on the day of discharge.",,"['Ellis, M E', 'Watson, B', 'Mandal, B K', 'Dunbar, E M', 'Craske, J', 'Curry, A', 'Roberts, J', 'Lomax, J']",,,,
,PMC,Latex immunoassay for rapid detection of rotavirus.,,PMC271347,,,"A latex agglutination (LA) test was evaluated for the detection of human rotaviruses in stool specimens. Both antiserum and immunoglobulin G (IgG)-sensitized latex particles were used, with IgG-coated beads being more sensitive for human rotavirus antigen detection. Latex beads sensitized with anti-simian-SA-11 IgG were stable for at least 8 months when stored at 4 degrees C. The sensitivity of the test was compared with that of the Rotazyme (Abbott Laboratories, Diagnostics Div., North Chicago, Ill.) test. The least number of particles detected was 9.0 X 10(5) particles by the LA test versus 4.5 X 10(5) particles by the Rotazyme test. When 10 stool specimens were serially diluted for antigen endpoint determinations, the geometric mean titer by the LA test was 592 versus 1,280 by the Rotazyme test. Forty-three stool samples positive by the Rotazyme test were all positive by the LA test, and no false negative results were detected. Unconfirmed false positive reactions ranged between 8 and 24%. The LA test for rotavirus antigen detection is direct, easy to perform, sensitive, quick, and may have application for use in diagnostic laboratories, emergency rooms, and physician's offices.",,"['Hughes, J H', 'Tuomari, A V', 'Mann, D R', 'Hamparian, V V']",,,,
,PMC,"Comparison of enzyme-linked immunosorbent assay, DNA hybridization, hemagglutination, and electron microscopy for detection of canine parvovirus infections.",,PMC271332,,,"Canine fecal samples were analyzed by enzyme-linked immunosorbent assays (ELISA) by using monoclonal antibodies to the canine parvovirus hemagglutinating protein. These data were compared with results obtained with DNA hybridization assays, hemagglutination assays, and electron microscopy. The highest correlation was observed between the ELISA and the hemagglutination tests, with 94.4% of samples showing agreement. Lower correlation was obtained between ELISA and DNA hybridization tests (73.3%). Correlation between ELISA and electron microscopy was 60.9%. The studies indicated that the ELISA can be used as a sensitive and specific diagnostic assay for canine parvovirus infections.",,"['Teramoto, Y A', 'Mildbrand, M M', 'Carlson, J', 'Collins, J K', 'Winston, S']",,,,
,PMC,Isolation of cold-sensitive mutants of measles virus from persistently infected murine neuroblastoma cells.,,PMC255853,,,"Clone NS20Y of the mouse neuroblastoma C1300 was infected with wild-type Edmonston measles virus, and, after a transition to a carrier culture, became persistently infected. Persistently infected clones were derived and characterized morphologically by the appearance of multinucleate giant cells and nucleocapsid matrices in cytoplasm and nucleus, but very few budding virus particles. Antimeasles antibodies markedly suppressed the expression of viral antigens and giant cells, and the effect was totally reversible. When the cells were cultured at 33 degrees C, the number of giant cells began to diminish and ultimately disappeared; in contrast, when cultured at 39 degrees C, the cultures invariably lysed. Yields at 33 degrees C were ca. 2 logs lower than those at 39 degrees C. Cells cultured at 33 degrees C produced relatively high levels of interferon, whereas those at 39 degrees C produced little or no interferon. When the persistently infected cultures were exposed to anti-interferon alpha/beta serum at a nonpermissive temperature, there was a marked increase in multinucleate cells, suggesting that maintenance of the persistence state and its regulation by temperature may be related to the production of interferon. Viral isolates from cells cultured at 39 degrees C were obtained, and 90% of viral clones were found to be cold sensitive. Complementation studies with different viral clones indicated that the cold-sensitive defect was probably associated with the same genetic function. Western blot analysis of the persistently infected cells indicated a significant diminution and expression of all measles-specific proteins at a nonpermissive temperature. Infection of NS20Y neuroblastoma cells with the cold-sensitive virus isolates resulted in the development of an immediate persistent infection, whereas infection of Vero or HeLa cells resulted in a characteristic lytic infection, suggesting that the cold-sensitive mutants may be selected or adapted for persistent infection in cells of neural origin.",,"['Rager-Zisman, B', 'Egan, J E', 'Kress, Y', 'Bloom, B R']",,,,
,PMC,Antigenic characterization of human coronaviruses 229E and OC43 by enzyme-linked immunosorbent assay.,,PMC271280,,,"Human coronaviruses 229E and OC43 possess three distinct antigens each which are located in peplomer, membrane, and nucleoprotein virion subcomponents. Although specific antigens are associated with similar polypeptides in both viruses, neither shared antigens nor serological cross-reactions have been observed. These findings were confirmed by enzyme-linked immunosorbent assay; rabbit whole-virus-specific antisera reacted with dissociated homologous virus and each of its subcomponents, whereas antisera monospecific to separate subcomponents (peplomers, membrane, or core) recognized only their respective components. Since neither shared antigens nor serological cross-reactions were seen between the two viruses, the specificity of the assay was similar to that of crossed-immunoelectrophoresis, virus neutralization, and complement fixation assays. However, sensitivity was increased at least 1,000-fold; complement fixation antibody titers of 2,000 corresponded to enzyme-linked immunosorbent assay titers of 3,200,000. Similar results were obtained with human convalescent-phase sera. In addition, the most prevalent human antibodies were found to be directed against virion peplomers. However, specific antibodies to core antigens and lesser amounts to membrane antigens were found in the sera of patients, which showed significant antibody rises when purified virion subcomponents were used as antigens. Importantly, rises and declines in titers of antibody to one virus and its specific antigens were independent from levels of titers of antibody to the other virus.",,"Schmidt, O W",,,,
,PMC,Nephropathia epidemica in Norway: antigen and antibodies in rodent reservoirs and antibodies in selected human populations.,,PMC2129280,,,"Nephropathia epidemica (NE) antigen was detected by IFAT (indirect fluorescent antibody technique) in the lungs of 14 of 97 bank voles (Clethrionomys glareolus) collected in three endemic areas. The distribution of antigen positive voles within an endemic location was scattered. Antibodies to Korean hemorrhagic fever (KHF) virus antigens were detected by IFAT in 12 of 14 NE antigen positive bank voles and in 15 of 83 that were antigen negative. NE antigen positive voles exhibited higher antibody titres. Antibodies to KHF were demonstrated in sera from C. rutilus and C. rufocanus collected more than 200 km north of the distribution area for C. glareolus. It appears likely that these vole species can serve as virus vectors for NE cases occurring north of the bank vole area. NE antibodies cross-reacting with KHF virus seem to diminish with time after infection in some NE patients, while for others such cross-reacting antibodies were detected up to 12 years after the disease. Antibodies to KHF were detected in eight of 106 healthy forestry workers with no clinical history of NE. No serological cross-reactions were detected between NE/KHF antigens and representative Bunyaviridae present in Norway. NE/KHF-like viruses appear widespread in Norway, both within and outside of the distribution area of the bank vole.",,"['Traavik, T.', 'Sommer, A. I.', 'Mehl, R.', 'Berdal, B. P.', 'Stavem, K.', 'Hunderi, O. H.', 'Dalrymple, J. M.']",,,,
,PMC,Persistence of mouse hepatitis virus A59 RNA in a slow virus demyelinating infection in mice as detected by in situ hybridization.,,PMC254475,,,"Mouse hepatitis virus strain A59 produces chronic central nervous system demyelination in rodents. As late as 6 months after intracerebral inoculation of mice 4 to 6 weeks old, when infectious virus cannot be recovered and viral antigens cannot be detected in the central nervous systems and livers of these animals, primary demyelination is still evident. Using cloned virus-specific DNAs and the highly sensitive and specific technique of in situ hybridization, we have detected low levels of mouse hepatitis virus A59 RNA in the central nervous systems and livers of mice 10 months after inoculation. We suggest that viral persistence may play a role in mouse hepatitis virus A59-induced chronic demyelination.",,"['Lavi, E', 'Gilden, D H', 'Highkin, M K', 'Weiss, S R']",,,,
,PMC,"Antigenic relationships among proteins of bovine coronavirus, human respiratory coronavirus OC43, and mouse hepatitis coronavirus A59.",,PMC254449,,,"Antisera prepared against each of three single and one pair of major structural proteins of the bovine coronavirus (Mebus strain) were used in immunoblotting studies to measure cross-reactivity with the structural proteins of the human coronavirus OC43 and the mouse hepatitis coronavirus A59. We conclude that the bovine coronavirus is comprised of four major structural proteins, gp190 (normally present as 120- and 100-kilodalton subunits), gp140, pp52, and gp26. The human coronavirus OC43 has an antigenically homologous counterpart of similar molecular mass to each of these proteins. The mouse hepatitis coronavirus A59 has an antigenically homologous counterpart to only three of these proteins: gp190, pp52 and gp26. There is no counterpart in the mouse virus to the 140-kilodalton glycoprotein, the apparent hemagglutinin of the bovine coronavirus.",,"['Hogue, B G', 'King, B', 'Brian, D A']",,,,
,PMC,Biosynthesis of microvillar proteins.,,PMC1143996,,,,,"['Danielsen, E M', 'Cowell, G M', 'Norén, O', 'Sjöström, H']",,,,
,PMC,Prevalence of rotavirus and coronavirus antigens in the feces of normal cows.,,PMC1236076,,,"The prevalence of rotavirus and coronavirus shedding by adult cows was investigated using capture enzyme-linked immunosorbent assays. Fecal samples from 121 cows in a single herd were tested for the presence of rotavirus and coronavirus, either free or complexed with immunoglobulin. Free rotavirus was not detected in any samples while rotavirus-immunoglobulin complexes were detected in 53 of 121 (44%) samples tested. In contrast, free coronavirus was detected in six (5%) samples and coronavirus-immunoglobulin complexes were detected in 85 (70%) of the samples tested. Thus it appears that subclinical infection of cows by either of these viruses is common, possibly providing a source for infection of the neonate. These assays may therefore provide important information regarding the epidemiology of enteric virus infections and suggest means of improving management to prevent epidemics of neonatal diarrhea.",,"['Crouch, C F', 'Acres, S D']",,,,
,PMC,Comparative study of bovine rotavirus isolates by plaque assay.,,PMC1236062,,,"Rotaviruses were isolated on BSC-1 cells from counterimmunoelectrophoresis and/or electron microscopy positive intestinal contents from two asymptomatic and six diarrheic calves from Quebec. The plaque assay was performed using these lines and agar overlay medium containing trypsin and DEAE-dextran. This assay was used to compare the Quebec isolates to an attenuated American strain (NCDV) and another strain (TH) obtained from France. The NCDV strain produced plaques that were significantly larger than those produced by the TH strain. Three Quebec isolates produced plaques similar in size to TH strain, one isolate was similar to NCDV strain and another isolate produced larger plaques than those of both NCDV and TH strains. The other isolates induced the production of plaques that were not significantly different from those of NCDV or TH strains.",,"['Archambault, D', 'Roy, R S', 'Dea, S', 'Elazhary, M A']",,,,
,PMC,Hypoglycemia: a factor associated with low survival rate of neonatal piglets infected with transmissible gastroenteritis virus.,,PMC1236061,,,"The main purpose of this work was to study changes in the balance of fluids, electrolytes and blood metabolites in neonatal piglets with severe transmissible gastroenteritis. Six two day old conventional piglets were infected with transmissible gastroenteritis virus while six others were used as normal controls. Blood samples were collected in heparin when the infected piglets were moribund. The following variables were measured: packed red cell volume, total plasma protein and bicarbonate, blood pH, blood urea nitrogen and plasma glucose, creatinine, chloride, inorganic phosphorus, sodium, potassium, magnesium and calcium. Vomiting and diarrhea appeared 12 to 24 hours postinoculation in the infected piglets and they were moribund one or two days later. Before becoming moribund, most of the piglets fell rapidly into a lethargic and comatose state. The most evident changes in their blood variables were an increase in packed cell volume, total protein, blood urea nitrogen, phosphorus and magnesium levels and a decrease in pH and bicarbonate concentration as well as a severe hypoglycemia. The results suggest that severe hypoglycemia coupled with metabolic acidosis and dehydration might be an important factor contributing to the high mortality rates caused by transmissible gastroenteritis in neonatal piglets. The hypoglycemia results from a combination of the inadequate glucose metabolism inherent to neonatal piglets and the acute maldigestion and malabsorption resulting from the diffuse and severe villous atrophy induced by the virus.",,"['Drolet, R', 'Morin, M', 'Fontaine, M']",,,,
,PMC,"Antibody-dependent and spontaneous cell-mediated cytotoxicity against transmissible gastroenteritis virus infected cells by lymphocytes from sows, fetuses and neonatal piglets.",,PMC1236056,,,"The purpose of this study was to investigate the ontogeny in the pig of effector lymphocytes mediating antibody-dependent and spontaneous cell-mediated cytotoxicity against target cells infected with transmissible gastroenteritis virus. The same activities were also studied in sows in late pregnancy and early lactation. Peripheral blood lymphocytes and intraepithelial lymphocytes collected from piglets during the first week of life failed to mediate cytolysis as determined by chromium release assays, but significant activities developed during the second week and usually increased further by the sixth week. Peripheral blood lymphocytes collected from fetuses on the 109th gestation day failed to produce spontaneous cell-mediated cytotoxicity and only reacted in antibody-dependent cell-mediated cytotoxicity when contaminated with macrophages. The cytotoxic activities of peripheral blood lymphocytes from sows were lowest at parturition. It was concluded that impaired lymphocyte cytotoxicity in newborn piglets and parturient sows may contribute to their relatively high susceptibility to transmissible gastroenteritis.",,"['Cepica, A', 'Derbyshire, J B']",,,,
,PMC,Persistent infection with mouse hepatitis virus 3 in mouse lymphoid cell lines.,,PMC263677,,,"The sensitivity of mice to mouse hepatitis virus 3 (MHV3) varies according to strain, age, and immune status of the animals. In semisusceptible strains, mice surviving the acute phase of infection develop a chronic disease characterized by the occurrence of paralysis, virus persistence, and immunodeficiency. Persistent MHV3 infections established in vitro in YAC and RDM -4 mouse lymphoid cell lines were characterized by virus production, presence of cytoplasmic viral antigens, and cell lysis. The occurrence of cell ""crisis"" in YAC cells was manifested by a sharp increase in cell lysis and in the number of fluorescent cells and, concomitantly, by a marked decrease in virus titers. A relationship was observed among the percentage of fluorescent cells, cell lysis, and virus yield and was modulated by renewal of culture media, change in temperature, or inhibition of cellular RNA synthesis. Cell cloning and antibody treatment experiments indicated that viral transmission was performed by viral infection of newly permissive cells produced by the division of uninfected cells in the culture and not by transmission of viral information by infected dividing cells. The biological and biochemical properties of MHV3 variants derived from persistently infected YAC lymphoid cells were characterized. Thermosensitivity and thermolability of cloned viruses originating from persistently infected YAC cells, as well as parent virus suspensions, were studied. A similar heterogeneity was observed when YAC-derived cloned substrains (YAC-MHV3) were compared with parent-derived cloned viruses, indicating that no selection of temperature-sensitive mutants was induced in persistently infected YAC cells. However, the capacity of MHV3 to induce a lethal acute disease when injected into susceptible mice was lost very rapidly. The absence of pathogenicity was related to the induction of a subclinical infection which elicited defense mechanisms. These data suggest, therefore, that MHV3 replication in lymphoid cell lines leads to induction or selection of variants which maintain pathogenicity in vitro but display reduced pathogenic effects in vivo.",,"['Lamontagne, L M', 'Dupuy, J M']",,,,
,PMC,Localisation of enteropathogens in paraffin embedded tissue by immunoperoxidase.,,PMC498838,,,"An indirect immunoperoxidase technique has been used to identify enteropathogens in formol-sublimate fixed paraffin embedded sections of calf intestine. Infections with bovine rotavirus, bovine coronavirus, Newbury agent SRV -1, and K99+ Escherichia coli have been detected in the intestines from experimentally infected and conventially reared diarrhoeic or normal calves. The ability to visualize enteropathogenic agents in histological sections resulted in the demonstration of virus infected cells at sites not previously shown to be infected using the immunofluorescence technique.",,"['Parsons, K R', 'Wilson, A M', 'Hall, G A', 'Bridger, J C', 'Chanter, N', 'Reynolds, D J']",,,,
,PMC,Antibody against viruses in maternal and cord sera: non-specific inhibitors are found to higher titre on the maternal side of the circulation.,,PMC2129316,,,"Pregnancies were identified in which maternal IgG antibodies against rubella virus were not detectable by single radial haemolysis. Twenty paired maternal/cord sera were then tested for haemagglutination-inhibiting (HI) activity against rubella virus without kaolin pretreatment of the sera. In the absence of specific antibody, the HI activity observed could thus be ascribed to the effect of non-specific inhibitors. The HI activity in maternal sera was significantly (P less than 0.001) higher than that in cord sera. The 20 pairs of sera were similarly tested against a bunyavirus, an alphavirus and a flavivirus, both with and without kaolin pretreatment. The results showed non-specific inhibitors were found to higher titre in maternal sera, with the difference being statistically significant (P less than 0.001) for each of the three viruses.",,"['Griffiths, P. D.', 'Girdhar, D.', 'Fisher-Hoch, S.', 'Race, M. W.', 'Heath, R. B.']",,,,
,PMC,Human viral gastroenteritis.,,PMC373217,,,,,"['Cukor, G', 'Blacklow, N R']",,,,
,PMC,"Characterization of leader RNA sequences on the virion and mRNAs of mouse hepatitis virus, a cytoplasmic RNA virus.",,PMC345271,,,"Mouse hepatitis virus, which replicates in cytoplasm, contains leader RNA sequences at the 5' end of the virus-specific mRNAs. We have sequenced this leader RNA by synthesizing cDNA from a synthetic oligodeoxyribonucleotide primer (15-mer) that is complementary to the sequences at the junction site between the leader and body sequences of the mRNAs. The leader sequences on each mRNA have exactly the same size, which span approximately equal to 70 nucleotides. Leader cDNA fragments obtained from several mRNA species were sequenced and found to be identical. Computer analysis of the leader RNA sequences shows that they share extensive sequence homology with the long-terminal-repeat region of several mammalian sarcoma viruses, suggesting possible common functions. This is a novel case of spliced leader sequences in the mRNAs of a cytoplasmic virus. An identical leader sequence is also present at the 5' end of the virion genomic RNA. The leader RNA is thus probably encoded by the virion genomic RNA template and is fused to the different body sequences of the various mRNAs. Since conventional RNA splicing is not involved, a novel mechanism for fusing two noncontiguous RNA segments in the cytoplasm must be utilized during viral transcription. Several minor cDNA bands longer than the leader were also synthesized, suggesting the possible presence of partially homologous sequences in other parts of the genome RNA.",,"['Lai, M M', 'Baric, R S', 'Brayton, P R', 'Stohlman, S A']",,,,
,PMC,Astrovirus and Breda virus infections of dome cell epithelium of bovine ileum.,,PMC271143,,,"A bovine enteric virus antigenically related to the United Kingdom isolate of bovine astrovirus was isolated from diarrheic feces, also containing rotavirus, of a calf in Florida. The astrovirus infected cell cultures and the epithelial cells of domes in the ileum, and there was cross-immunofluorescence with antiserum to the United Kingdom astrovirus. Calves infected with astrovirus alone did not develop clinical disease, but when astrovirus was mixed with rotavirus or Breda virus 2, the calves developed severe diarrhea and more extensive astrovirus infection of the dome epithelium. The dome epithelial cells showed degeneration associated with astrovirus infection, and a few cells showed degeneration with Breda virus 2 infection. Virions with a 30-nm diameter were seen in astrovirus-infected dome cells, and Breda virus 2 virions were also observed either in separate cells or, on occasion, with both viruses in one cell.",,"['Woode, G N', 'Pohlenz, J F', 'Gourley, N E', 'Fagerland, J A']",,,,
,PMC,Respiratory virus infections and aeroallergens in acute bronchial asthma.,,PMC1628687,,,"Two hundred and fifty six attacks of acute bronchial asthma occurring in 169 children aged over 2 years were studied during a two year period. More attacks occurred during spring and autumn than at other times of the year. In 73 patients (29%) a respiratory virus infection was diagnosed, with the same seasonal variation as the asthmatic attacks. Most of the virus infections were caused by rhinovirus (45%) and respiratory syncytial virus (19%). There was no significant correlation between asthmatic attacks in patients with birch pollen, grass pollen, or Cladosporium herbarum allergy and counts of the respective pollen or spores in the air. More seasonal attacks occurred in patients with cladosporium allergy than in patients without cladosporium allergy but there was no seasonal variation among birch or grass pollen allergic patients. Information about exposure to animals was obtained in only 12% of attacks occurring in 121 patients with allergy to animal dander. The single precipitating factor most frequently associated with acute asthma was respiratory virus infection.",,"['Carlsen, K H', 'Orstavik, I', 'Leegaard, J', 'Høeg, H']",,,,
,PMC,Production of cattle immunotolerant to bovine viral diarrhea virus.,,PMC1236029,,,"Inoculation of bovine virus diarrhea virus into 58 to 125 day old fetuses of bovine virus diarrhea virus seropositive pregnant cows, or inoculation of bovine virus diarrhea virus into seronegative cows 42 to 114 days pregnant, may produce clinically normal calves which are persistently infected with the specific isolate of bovine virus diarrhea virus yet seronegative to the homologous and heterologous isolates. Reinoculation of these persistently infected cattle with their homologous isolate produced no neutralizing antibody response to bovine virus diarrhea virus. These persistently infected cattle were immunocompetent as they developed neutralizing serotiters to infectious bovine rhinotracheitis, parainfluenza-3 viruses and agglutinating serotiters to Pasteurella hemolytica .",,"['McClurkin, A W', 'Littledike, E T', 'Cutlip, R C', 'Frank, G H', 'Coria, M F', 'Bolin, S R']",,,,
,PMC,Coronavirus multiplication: locations of genes for virion proteins on the avian infectious bronchitis virus genome.,,PMC255576,,,"Six overlapping viral RNAs are synthesized in cells infected with the avian coronavirus infectious bronchitis virus (IBV). These RNAs contain a 3'-coterminal nested sequence set and were assumed to be viral mRNAs. The seven major IBV virion proteins are all produced by processing of three polypeptides of ca. 23, 51, and 115 kilodaltons. These are the core polypeptides of the small membrane proteins, the nucleocapsid protein, and the 155-kilodalton precursor to the large membrane proteins GP90 and GP84, respectively. To determine which mRNAs specify these polypeptides, we isolated RNA from infected cells and translated it in a messenger-dependent rabbit reticulocyte lysate. Proteins of 23, 51, and 110 kilodaltons were produced. Two-dimensional tryptic peptide mapping demonstrated that these proteins were closely related to the major virion proteins. Fractionation of the RNA before cell-free translation permitted the correlation of messenger activities for synthesis of the proteins with the presence of specific mRNAs. We found that the smallest RNA, RNA A, directs the synthesis of P51, the nucleocapsid protein. RNA C, which contains the sequences of RNA A, directs the synthesis of the small membrane protein P23. RNA E directs the synthesis of the large virion glycoproteins. These results supported a model in which only the unique 5'-terminal domain of each IBV mRNA is active in translation and enabled us to localize genes for virion proteins on the IBV genome.",,"['Stern, D F', 'Sefton, B M']",,,,
,PMC,The carbohydrates of mouse hepatitis virus (MHV) A59: structures of the O-glycosidically linked oligosaccharides of glycoprotein E1.,,PMC557404,,,"Two size classes of O-glycosidically linked oligosaccharides were liberated from glycoprotein E1 of mouse hepatitis virus (MHV) A59 by reductive beta-elimination and separated by h.p.l.c. The structures of the reduced oligosaccharides were determined by successive exoglycosidase digestions and by methylation analyses involving combined capillary gas chromatography-mass spectrometry and mass fragmentography after chemical ionization with ammonia. Oligosaccharide A (Neu5Ac alpha 2----3 Gal beta 1----3 GalNAc) comprised 35% of the total carbohydrate side chains, while the remaining 65% of the oligosaccharides of E1 had the branched structure B: Neu5Ac alpha 2----3 Gal beta 1----3 (Neu5Ac alpha 2----6) GalNAc. Both oligosaccharides were linked to the E1 polypeptide via N-acetylgalactosamine, and 20% of the sialic acids present in E1 glycopeptides were found to consist of N-acetyl-9-mono-O-acetylneuraminic acid. The reported structures of the O-linked glycans are discussed in the context of the amino acid sequence of E1, which exhibits a cluster of four hydroxyamino acids (Ser-Ser-Thr-Thr) as potential O-glycosylation sites at the amino terminus. Oligosaccharides with identical structures and an identical O-glycosylated tetrapeptide sequence are present in the blood group M-active glycophorin A of the human erythrocyte membrane.",,"['Niemann, H', 'Geyer, R', 'Klenk, H D', 'Linder, D', 'Stirm, S', 'Wirth, M']",,,,
,PMC,Effects of environmental and dietary factors on human rotavirus infection in gnotobiotic piglets.,,PMC264269,,,"The addition of proteolytic enzyme to diets fed to newborn gnotobiotic piglets exacerbated their diarrheal response after oral infection with human rotaviruses. Supplementation of diets with proteolytic enzyme and reduced ambient temperature were evaluated for effects upon the clinical response of gnotobiotic piglets infected with human rotavirus Wa strain, type 2. Piglets were divided into four treatment groups combining two variables: ambient temperature of 35 or 26 degrees C, with and without proteolytic enzyme supplementation of the diet. Infected piglets maintained at 26 degrees C with and without enzyme supplementation had 90 and 70% mortality, respectively. No mortality was observed in infected piglets maintained at 35 degrees C. Protease supplementation of diets fed to piglets kept at 35 degrees C resulted in more uniform onset of diarrhea of greater severity than in littermates fed diets without the supplementation.",,"['Steel, R B', 'Torres-Medina, A']",,,,
,PMC,Role of recent vaccination in production of false-positive coronavirus antibody titers in cats.,,PMC271086,,,"Statistical support was obtained for an association between recent vaccination of cats and the presence of elevated background (i.e., anti-cell culture) reactivity in certain of their sera, as detected with a kinetics-based enzyme-linked immunosorbent assay for coronavirus antibodies, implicating routine vaccination as a potential cause of false-positive antibody test results.",,"['Barlough, J E', 'Jacobson, R H', 'Pepper, C E', 'Scott, F W']",,,,
,PMC,Monoclonal antibody capture enzyme-linked immunosorbent assay for detection of bovine enteric coronavirus.,,PMC271071,,,"Monoclonal antibodies reactive with three different viral polypeptides were evaluated singly and in combination as the capture antibody(s) in an enzyme-linked immunosorbent assay system for the detection of bovine enteric coronavirus. Similar levels of sensitivity were found for all combinations tested. A sensitive, highly specific, and reproducible assay for the detection of bovine enteric coronavirus was developed, using a mixture of two of these monoclonal antibodies reactive with antigenic components either external or internal to the virion. These monoclonal antibodies were bound indirectly to 96-well plates via rabbit anti-mouse immunoglobulin. After sample application and incubation, virus was detected by using rabbit anti-coronavirus peroxidase conjugate followed by enzyme substrate and chromagen. Fecal samples from a single herd of cows were screened for the presence of coronavirus by this assay. Five percent of clinically normal cows were found to be shedding coronavirus.",,"['Crouch, C F', 'Raybould, T J', 'Acres, S D']",,,,
,PMC,Assembly in vitro of a spanning membrane protein of the endoplasmic reticulum: the E1 glycoprotein of coronavirus mouse hepatitis virus A59.,,PMC344847,,,"The E1 glycoprotein of coronavirus mouse hepatitis virus A59 was synthesized in vitro by translation of viral mRNA in the presence of dog pancreatic microsomes. Its disposition in the membrane was investigated by digestion with proteases and by selective NH2-terminal labeling. The protein spans the membrane, but only small portions from the NH2 and COOH terminus are exposed respectively in the lumenal and cytoplasmic domains; the bulk of the molecule is apparently buried in the membrane. The protein lacks a cleavable leader sequence and does not acquire its characteristic O-linked oligosaccharides in rough microsomes. It may enter the membrane at any stage during synthesis of the first 150 amino acid residues. These unusual features of the protein might help to explain why it is not transported to the cell surface in vivo but remains in intracellular membranes, causing the virus to bud there.",,"['Rottier, P', 'Brandenburg, D', 'Armstrong, J', 'van der Zeijst, B', 'Warren, G']",,,,
,PMC,Infection and interferon production in systemic juvenile chronic arthritis: a prospective study.,,PMC1001206,,,"Twenty-four episodes of disease exacerbation in 19 children suffering from systemic juvenile chronic arthritis were studied. Sixteen of these were preceded by an infection (chi 2 = 20.14, p less than 0.001), mostly of the upper respiratory tract. In the 10 cases seen during an infection causative agents were identified in 5 (herpes simplex, rhinovirus, and on 3 occasions streptococcus). The total number of infections was not increased when compared with infection rates predicted by several reported studies. In the absence of clinical infection, specific antibody titres to a panel of microbial antigens were similar to those of a control group but with a trend toward higher titres in patients with hypergammaglobulinaemia. Interferon (IFN) responses were not defective, though sequential in-vitro IFN production from peripheral blood mononuclear cells (PBM) fluctuated considerably in the same patients, occasionally being absent with no obvious clinical correlate. IFN-alpha was induced by stimulation with Newcastle disease virus (NDV), and the mean responses of the patients were significantly greater than those of controls. IFN-gamma production on phytohaemagglutinin (PHA) stimulation was similar in patients and control groups. IFN was not detected in any of the sera from patients or controls.",,"['de Vere-Tyndall, A', 'Bacon, T', 'Parry, R', 'Tyrrell, D A', 'Denman, A M', 'Ansell, B M']",,,,
,PMC,Serotyping of cell culture-adapted subgroup 2 human rotavirus strains by neutralization.,,PMC264360,,,"Nine human rotavirus strains from stools of infants with gastroenteritis were serially propagated in MA-104 cell cultures. All strains were identified as subgroup 2 rotaviruses by RNA gel electrophoresis, complement fixation, and enzyme-linked immunosorbent assay. The human rotavirus strains were propagated for 15 to 20 passages and then used for immunization of guinea pigs and rabbits. Animal antisera were also raised against a subgroup 1 human strain purified from stools and against the cell culture-adapted Wa strain, a reference subgroup 2 rotavirus of human origin. Cross-neutralization studies revealed the existence of two distinct serotypes within the cell culture-adapted subgroup 2 human rotaviruses: strains related and unrelated to strain Wa were classified as serotypes 1 and 3, respectively. Results with convalescent-phase sera from infants with primary rotavirus infections confirmed the existence of two serotypes within subgroup 2, and the serotypes responsible for primary subgroup 2 infections could be determined on the basis of the neutralizing reactivity of convalescent sera.",,"['Gerna, G', 'Battaglia, M', 'Milenesi, G', 'Passarani, N', 'Percivalle, E', 'Cattaneo, E']",,,,
,PMC,"Microvolume, kinetic-dependent enzyme-linked immunosorbent assay for amoeba antibodies.",,PMC271025,,,"We describe a microvolume enzyme-linked immunosorbent assay based on enzyme rate kinetics. Antigens from Entamoeba histolytica were adsorbed in wells of disposable polystyrene strips containing 12 flat-bottom wells. After exposure to the serum of a patient and peroxidase-labeled anti-human immunoglobulin G, the rate of color change in specific substrate was determined by eight sequential readings of individual wells over a 2-min period with a microcomputer-controlled model MR-600 automated plate reader. The changes in absorbance readings were converted to slope values for each well by the microcomputer. Thus, 12 samples were read, and results were printed in ca. 3.5 min. Assay conditions are described and data are presented to show that this assay is quantitative for antibody and antigen concentration with a single-tube (well) dilution.",,"['Mathews, H M', 'Walls, K W', 'Huong, A Y']",,,,
,PMC,Un programme de lutte contre les infections aiguës des voies respiratoires chez les enfants: Mémorandum d'une Réunion de l'OMS.,,PMC2536306,,,,,,,,,
,PMC,RNA electropherotypes of human rotaviruses from North and South America,,PMC2536299,,,"Between April 1979 and December 1982, viral agents were found in 231 of 695 children admitted to the Texas Children's Hospital with gastroenteritis. Electron microscopic analysis showed that rotaviruses were the most common viral agents, and a seasonal pattern of rotavirus disease was observed. The migration patterns of the RNA segments of these rotaviruses on electrophoresis in polyacrylamide gels were compared with those of rotaviruses collected from other areas of the United States of America and from Argentina, Colombia and Mexico. A number of different RNA electropherotypes were found, including some patterns not previously reported.",,"['Dimitrov, D. H.', 'Graham, D. Y.', 'Lopez, J.', 'Muchinik, G.', 'Velasco, G.', 'Stenback, W. A.', 'Estes, M. K.']",,,,
,PMC,A programme for controlling acute respiratory infections in children: Memorandum from a WHO Meeting,,PMC2536276,,,"The unacceptably high mortality related to acute respiratory infections (ARI) in children, recognition of the importance of bacteria in the causation of severe acute lower respiratory infection in developing countries, and the established effectiveness of antimicrobial and supportive treatment in averting death make a strong case for the initiation of an ARI control programme. This should be spearheaded by prototype ARI service activities, delivered through primary health care and backed up by well-coordinated health systems research.",,,,,,
,PMC,Characterization of a calici-like virus (Newbury agent) found in association with astrovirus in bovine diarrhea.,,PMC263399,,,"A bovine calici-like virus and astrovirus, present in the same fecal sample from an outbreak of diarrhea, were separated from each other by calf passage. The calici-like virus (Newbury agent SRV-1) caused anorexia, diarrhea, and xylose malabsorption in gnotobiotic calves aged 17 to 60 days, whereas the bovine astrovirus was nonpathogenic in similar calves. The calici-like virus was shown to be antigenically distinct from a previously described isolate (Newbury agent SRV-2) by two-way cross-protection experiments in calves; calves immune to homologous challenge became clinically ill and excreted virus when challenged with the heterologous virus.",,"['Bridger, J C', 'Hall, G A', 'Brown, J F']",,,,
,PMC,"Immune response to porin in cattle immunized with whole cell, outer membrane, and outer membrane protein antigens of Brucella abortus combined with trehalose dimycolate and muramyl dipeptide adjuvants.",,PMC264420,,,"The immune response of cattle to nonliving vaccines derived from Brucella abortus rough strain 45/20 was studied. Vaccines contained trehalose dimycolate and a derivative of muramyl dipeptide. N-acetylmuramyl-L-alpha-aminobutyryl-D-isoglutamine. A factorial experiment was designed to test the effects of type of antigen, quantity of antigen, and quantity of mineral oil on the immune response to porin. Muramyl dipeptide was kept constant at 5 mg per dose, and 1 part of trehalose dimycolate was incorporated for two parts of dry matter. Over a 10-week period, blastogenesis responses to porin were largest in cattle immunized with outer membranes; the highest antibody titers to the porin-lipopolysaccharide complex were achieved by immunization with detergent-extracted outer membrane proteins. There was no advantage in the use of 25, rather than 5, mg of any of the antigens, but antibody responses were improved by increasing the quantity of oil from 0.6 to 1.8 ml per dose. In other animals, blastogenesis and antibody responses were sustained at high levels longer than 3 months after two vaccinations with outer membrane proteins. Intradermal injection of porin evoked inflammatory reactions histologically consistent with delayed-type hypersensitivity. Cross-reactions in cases of delayed-type hypersensitivity occurred with porin derived from a smooth strain of B. abortus but were less extensive than in the blastogenesis test. The magnitude of the delayed-type hypersensitivity and blastogenesis responses induced by vaccination exceeded those observed after natural or experimental infections. No ill effects were observed after vaccination. These findings provide a basis for the use of trehalose dimycolate and muramyl dipeptide adjuvants in evaluating nonviable vaccines for bovine brucellosis.",,"['Winter, A J', 'Verstreate, D R', 'Hall, C E', 'Jacobson, R H', 'Castleman, W L', 'Meredith, M P', 'McLaughlin, C A']",,,,
,PMC,Characterization of replicative intermediate RNA of mouse hepatitis virus: presence of leader RNA sequences on nascent chains.,,PMC255394,,,"Mouse hepatitis virus A59 codes for seven mRNAs in infected cells. These mRNAs are transcribed from a minus (-) strand template of genome length and contain a leader RNA at their 5' ends. To further elucidate the mechanism of coronavirus transcription, we examined the structure of mouse hepatitis virus replicative intermediates (RIs) isolated by 2 M NaCl precipitation and Sepharose 2-B column chromatography. Purified RIs migrated as a single species on agarose gels and sedimented between 12 and 38S on 10 to 25% sucrose gradients. The complexes were readily heat denatured into a heterogeneous population of smaller RNA molecules which probably represent nascent plus (+) strands. RNase A digestion of RIs produced a single replicative form which sedimented between 30 and 32S. These data suggest that the RI is composed of a single genome-sized (-) strand hydrogen bonded to an average of 4 to 6.5 nascent (+) strands. In contrast, a column-purified replicative form was extremely resistant to RNase A digestion and heat denaturation and migrated as a single RNA species on agarose gels and sucrose gradients. Oligonucleotide fingerprinting of an RI revealed the presence of the 5' leader RNA on the nascent (+) strands. In addition, an average of 6.2 cap structures were present in each RI, which agrees with the average number of nascent (+) strands per RI. These data suggest that the leader RNA is utilized as a primer for mouse hepatitis virus RNA transcription and is not added to mRNA post-transcriptionally.",,"['Baric, R S', 'Stohlman, S A', 'Lai, M M']",,,,
,PMC,Biosynthesis of intestinal microvillar proteins. The effect of swainsonine on post-translational processing of aminopeptidase N.,,PMC1152508,,,"The post-translational processing of pig small-intestinal aminopeptidase N (EC 3.4.11.2) was studied in organ-cultured mucosal explants. Exposure of the explants to swainsonine, an inhibitor of Golgi mannosidase II, resulted in the formation of a Mr-160000 polypeptide, still sensitive to endo-beta-N-acetylglucosaminidase H. Swainsonine caused only a moderate inhibition of transport of the enzyme through the Golgi complex and the subsequent expression in the microvillar membrane. This may imply that the trimming of the high-mannose core and complex glycosylation of N-linked oligosaccharides is not essential for the transport of aminopeptidase N to its final destination. A different type of processing was observed to take place in the presence of swainsonine, resulting in a considerable increase in apparent Mr (from 140000 to 160000). This processing could not be ascribed to N-linked glycosylation, since treatment of the Mr-160000 polypeptide with endo-beta-N-acetylglucosaminidase H only decreased its apparent Mr by 15000. The susceptibility of the mature Mr-166000 polypeptide, but not the Mr-140000 polypeptide, to mild alkaline hydrolysis suggests that aminopeptidase N becomes glycosylated with O-linked oligosaccharides during its passage through the Golgi complex. Aminopeptidase N was not labelled by [3H]palmitic acid, indicating that the processing of the enzyme does not include acylation.",,"['Danielsen, E M', 'Cowell, G M', 'Norén, O', 'Sjöström, H', 'Dorling, P R']",,,,
,PMC,Intranasal interferon as protection against experimental respiratory coronavirus infection in volunteers.,,PMC185930,,,"In a double-blind, placebo-controlled study, self-administered intranasal human interferon alpha A produced by recombinant DNA technology was given both before and after virus challenge with a respiratory coronavirus. The incidence of colds, the severity of symptoms and signs, and virus replication were all reduced in subjects receiving interferon as compared with those given placebo.",,"['Higgins, P G', 'Phillpotts, R J', 'Scott, G M', 'Wallace, J', 'Bernhardt, L L', 'Tyrrell, D A']",,,,
,PMC,Protection of calves against fatal enteric colibacillosis by orally administered Escherichia coli K99-specific monoclonal antibody.,,PMC264479,,,"A monoclonal antibody (MCA) to enterotoxigenic Escherichia coli K99 antigen agglutinated K99+ enterotoxigenic E. coli strains B44 (O9:K30;K99;F41:H-) and B41 (O101:K99;F41:H-) grown at 37 degrees C but not at 18 degrees C. The MCA, which was characterized as immunoglobulin G1, reacted specifically with K99 antigen in an enzyme-linked immunosorbent assay and precipitated radiolabeled K99 antigen. A total of 45 colostrum-fed and colostrum-deprived calves were used in three separate trials to determine whether the orally administered K99-specific MCA would prevent diarrhea caused by strain B44. Twenty-eight calves were fed 1 ml of mouse ascitic fluid containing K99-specific MCA at 10 h of age and were orally challenged with strain B44 at 12 to 14 h of age. Control calves either received no placebo or were fed 1 ml of mouse ascitic fluid containing fibronectin-specific MCA at 10 h of age. There was no difference in the incidence of diarrhea between the two groups after challenge. However, the severity of diarrhea, as evaluated by the proportion of calves in each group that developed severe dehydration, the degree of clinical dehydration, the degree of clinical depression, the degree of weight loss, and the duration of diarrhea after challenge was significantly reduced in calves that received the K99-specific MCA. The mortality rate was also significantly lower (P less than 0.001) in the treated (29%) than in the control (82%) group. These results suggest that orally administered K99-specific MCA can prevent severe fatal enteric colibacillosis.",,"['Sherman, D M', 'Acres, S D', 'Sadowski, P L', 'Springer, J A', 'Bray, B', 'Raybould, T J', 'Muscoplat, C C']",,,,
,PMC,Evaluation of murine cytomegalovirus antibody detection by serological techniques.,,PMC270900,,,"Naturally acquired murine cytomegalovirus (MCMV) infection in laboratory strains of mice induces antibody levels which are generally undetectable by standard techniques; therefore, MCMV has not been included routinely in mouse viral antibody screening programs. The relative sensitivity of three assay systems, the nuclear anticomplement immunofluorescence (NACIF), the enzyme-linked immunosorbent assay (ELISA), and the complement fixation (CF) test, was evaluated for the detection of MCMV antibodies. Sera were harvested from CD1 male mice (33 days old) infected intraperitoneally with salivary gland-passaged MCMV (Smith strain). The sera were assayed separately at weeks 1 through 8, and at week 11, 16, and 25 post-inoculation; a total of 167 mice in 11 groups were tested. The animals tested at 1 week post-inoculation had low levels of antibodies to MCMV as measured by the NACIF test (1:10), whereas only 25% were positive by ELISA, and none was positive by CF until 5 weeks post-inoculation. A higher titer of MCMV antibodies was measured by CF (1:640) than by NACIF (1:40) at 6 months post-inoculation; yet, a titer of 1:3,200 was detected by ELISA from the same serum. The ELISA technique was more sensitive for detecting persistent infection with MCMV, and NACIF was more useful for detecting acute MCMV infection. Since MCMV can have significant long-term effects on the immune system, it is recommended that testing for antibodies to MCMV be included in mouse viral antibody screening protocols.",,"['Anderson, C A', 'Murphy, J C', 'Fox, J G']",,,,
,PMC,N-acetylgalactosaminyltransferase activity involved in O-glycosylation of herpes simplex virus type 1 glycoproteins.,,PMC255351,,,"We report on N-acetylgalactosaminyltransferase (UDPacetylgalactosamine--protein acetylgalactosaminyltransferase; EC 2.4.1.41) activity in herpes simplex virus type 1 (HSV-1)-infected BHK and RicR14 cells, a line of ricin-resistant BHK cells defective in N-acetylglucosaminyltransferase I. The enzyme catalyzed the transfer of [14C]N-acetylgalactosamine (GalNAc) from UDP-[14C]GalNAc into HSV glycoproteins, as identified by immunoprecipitation. The sugar was selectively incorporated into the immature forms of herpesvirus glycoproteins pgC, pgD, and gA-pgB, which are known to contain N-linked glycans of the high-mannose type. The high incorporation of [14C]GalNAc into endogenous acceptors of HSV-1-infected RicR14 cells was consistent with the accumulation of immature forms of HSV glycoproteins which occurs in these cells. Mild alkaline borohydride treatment of glycoproteins labeled via GalNAc transferase showed that the transferred GalNAc was O-linked and represented the first sugar added to the peptide backbone.",,"['Serafini-Cessi, F', ""Dall'Olio, F"", 'Scannavini, M', 'Costanzo, F', 'Campadelli-Fiume, G']",,,,
,PMC,Amino acid sequence of human respiratory syncytial virus nucleocapsid protein.,,PMC326328,,,"Amino acid sequence of the human respiratory syncytial (RS) virus nucleocapsid (NC) protein, deduced from the DNA sequence of a recombinant plasmid, is presented. The cDNA plasmid (pRSB11) has 1412 bp of RS viral NC sequence and lacks six nucleotides of the 5' end of mRNA. There is a single long open reading frame encoding 467 amino acids. This 51540 dal protein is rich in basic amino acids and has no homologies with other known viral capsid proteins.",,"['Elango, N', 'Venkatesan, S']",,,,
,PMC,Passive immunity to bovine rotavirus in newborn calves fed colostrum supplements from immunized or nonimmunized cows.,,PMC264616,,,"Colostrum was collected and pooled from each of five cows in three experimental groups: group I cows received intramuscular and intramammary inoculations of adjuvanted modified live Ohio Agricultural Research and Development Center rotavirus vaccine; group II cows were injected intramuscularly with a commercial modified-live rota-coronavirus vaccine; and group III cows were uninoculated controls. Pooled colostrum from group I cows had higher (P less than 0.05) enzyme-linked immunosorbent assay (ELISA) immunoglobulin G (IgG1) and virus neutralization (VN) rotavirus antibody titers (ELISA IgG1 = 2,413,682; VN = 360,205) than did colostrum from group II (ELISA IgG1 = 8,192; VN = 4,395) or group III cows (ELISA IgG1 = 5,916; VN = 2,865). The antibody titers of these last two colostrum pools did not differ (P greater than 0.05). Samples of these colostrum pools were fed as daily supplements (percent [vol/vol] in cow's milk infant formula) to 28 newborn, unsuckled, antibody-seronegative, male Holstein calves. Eight calves received no supplemental colostrum. The calves were orally challenged with virulent bovine rotavirus and monitored daily for diarrhea and fecal rotavirus shedding. Diarrhea and rotavirus shedding occurred in the eight calves fed no supplemental colostrum and persisted longest in this group. The pooled colostrum from group I cows protected eight of eight calves from both rotavirus diarrhea and shedding when fed as a 1% supplement. The pooled colostrum from neither group II nor group III cows protected 12 other calves against rotavirus diarrhea or shedding when fed at the same concentration (1%). Six rotavirus-challenged calves fed 0.1% supplemental colostrum from group I cows and two calves fed 10 and 50% supplemental colostrum from control cows displayed partial passive immunity, exemplified by delayed onset and shortened duration of rotavirus-associated diarrhea and virus shedding.",,"['Saif, L J', 'Redman, D R', 'Smith, K L', 'Theil, K W']",,,,
,PMC,"Isolation, propagation, and characterization of a second equine rotavirus serotype.",,PMC264604,,,"A rotavirus designated strain H-2 was isolated in primary African green monkey kidney cells from a foal with diarrhea. This cell culture-adapted strain was found to be similar, if not identical, to simian rotavirus (strains MMU18006 and SA-11) and canine rotavirus (strain CU-1) and, in addition, demonstrated a one-way antigenic relationship with five human rotavirus strains (P, B, no. 14, no. 15, and YO) of the third human rotavirus serotype by the plaque reduction neutralization test. This is the fifth example of an animal rotavirus which shares serotypic specificity with a human rotavirus. The H-2 strain is distinct from the H-1 strain (Y. Hoshino et al., J. Clin. Microbiol., in press) of equine rotavirus not only in serotypic specificity by neutralization but also in subgroup specificity, hemagglutinating activity, and RNA electrophoretic migration pattern, thus establishing the existence of a second equine rotavirus serotype. This H-2 isolate is also distinct by neutralization from three other human rotavirus serotypes, 1 (Wa), 2 (DS-1), and 4 (St. Thomas no. 4), as well as bovine (NCDV), and porcine (OSU) rotaviruses.",,"['Hoshino, Y', 'Wyatt, R G', 'Greenberg, H B', 'Kalica, A R', 'Flores, J', 'Kapikian, A Z']",,,,
,PMC,Rotavirus as a cause of severe gastroenteritis in adults.,,PMC270871,,,"Rotavirus was identified as the only etiological agent in 5% of adults (28 of 526) with diarrhea who were admitted to Bamrasnaradura Hospital in Nonthaburi, Thailand, during a 1-year period. Infection was determined by detection of rotavirus in diarrheal stools by enzyme-linked immunosorbent assay accompanied by a greater than fourfold rise in serum complement fixation and radioimmunoassay antibody titers to rotavirus. Adults with clinical rotavirus infections were as severely ill as patients with most bacterial enteric infections; only patients with cholera passed more watery stools and were more dehydrated than those with rotavirus infections. Only 2 of the 28 adults with rotavirus infections had known recent contact with young children with diarrhea. Rotavirus infections in these adults occurred most frequently in the cooler, drier months in Thailand than during the rest of the year. In some settings, rotavirus should be considered in the differential diagnosis of severe diarrhea in adults as well as in young children.",,"['Echeverria, P', 'Blacklow, N R', 'Cukor, G G', 'Vibulbandhitkit, S', 'Changchawalit, S', 'Boonthai, P']",,,,
,PMC,Isolation and characterization of an equine rotavirus.,,PMC270858,,,"A rotavirus, designated as the H-1 strain, was isolated from a diarrheic foal in primary African green monkey kidney cells and MA104 cells. This cell culture-adapted strain hemagglutinated erythrocytes of human group O, rhesus monkeys, guinea pigs, and sheep. It was found to be similar, if not identical, to porcine rotaviruses (strains OSU, EE, and A-580) by plaque reduction neutralization and hemagglutination inhibition tests, and, in addition, it was found to belong to subgroup 1. This equine rotavirus has an RNA electrophoretic migration pattern which was distinct from those of the three strains of porcine rotavirus. The serological relationship established by plaque reduction neutralization and hemagglutination inhibition tests between the equine (H-1) and porcine (OSU, EE, and A-580) rotaviruses is an example of a rotavirus of the same serotype being isolated from different species. The H-1 strain was distinct from four human rotavirus serotypes (Wa, DS-1, P, and St. Thomas 4) as well as from bovine rotavirus NCDV, simian rotavirus MMU18006, and canine rotavirus CU-1 by plaque reduction neutralization tests. This equine isolate (H-1) was found to be related antigenically to canine CU-1 and bovine NCDV rotaviruses in a one-way fashion by hemagglutination inhibition tests.",,"['Hoshino, Y', 'Wyatt, R G', 'Greenberg, H B', 'Kalica, A R', 'Flores, J', 'Kapikian, A Z']",,,,
,PMC,Coronavirus JHM: nucleotide sequence of the mRNA that encodes nucleocapsid protein.,,PMC326236,,,"A DNA copy of the mRNA that encodes the nucleocapsid protein of Mouse Hepatitis Virus JHM has been cloned into pAT153. The DNA copy specifically inhibited the synthesis in vitro of the nucleocapsid protein. The cDNA was subcloned into M13 vectors and the entire sequence, 1767 bases including a 15 base terminal poly (A) tract, has been determined by chain-terminator sequencing. The sequence contained an open-reading frame that could encode a basic protein of mol.wt. 49700. From the predicted sequence it was apparent that the nucleocapsid protein has 5 basic regions, two of which are located near the middle of the sequence, a serine-rich region was also located, a feature which may be of functional importance as the nucleocapsid protein is phosphorylated at serine residues. The carboxy terminus of the nucleocapsid protein was found to be acidic. The 5' non-coding sequence contained a triple repeat of the pentamer AATCT, a structural feature which may play a significant role during the production of subgenomic viral mRNAs.",,"['Skinner, M A', 'Siddell, S G']",,,,
,PMC,Antigenic relationships among some bovine rotaviruses: serum neutralization and cross-protection in gnotobiotic calves.,,PMC270805,,,"A method was further developed to screen non-tissue-culture-adapted bovine rotaviruses for serotype, using a neutralization test with infectious fecal rotavirus. One of those rotaviruses (B223) which was not blocked by antiserum to the neonatal calf diarrhea virus (NCDV) serotype was then adapted to cell culture in the presence of the antiserum for two or more passages and hyperimmune antiserum to this isolate had a 60-fold-higher homologous neutralization titer than with the NCDV serotype rotavirus. Seventy-three isolates were serotyped and eight (11%) were not of the NCDV serotype (bovine rotavirus serotype I). Of these eight, five belonged to the new bovine rotavirus serotype II and three were not typed, indicating the existence of one or more further serotypes. Cross-protection studies in gnotobiotic calves showed that cross-protection only occurred between rotaviruses of the same serotype, and even a minor serotype difference was sufficient for the calves to show a lack of cross-protection. The serotypes (I and II and the three untyped isolates) also showed differences in the rate of migration in polyacrylamide gel electrophoresis of some of their RNA segments (no. 4, 6, 7, 8, 9, 10), indicating that they were of different electropherotypes.",,"['Woode, G N', 'Kelso, N E', 'Simpson, T F', 'Gaul, S K', 'Evans, L E', 'Babiuk, L']",,,,
,PMC,Epidemiology of coronavirus respiratory infections.,,PMC1628163,,,"Human coronaviruses were found by enzyme linked immunosorbent assay in upper respiratory tract secretions taken during 30% of 108 acute respiratory infections experienced by 30 children under age 6 years with recurrent respiratory infections (index group), and during 29% of 51 acute infections experienced by their siblings. Lower respiratory tract infection--predominantly wheezy bronchitis--occurred in 30% of the index children's coronavirus positive infections but in none of their siblings' infections. Reinfections were common. Two peaks of infection were seen each year in the late autumn/early winter and in the early summer.",,"['Isaacs, D', 'Flowers, D', 'Clarke, J R', 'Valman, H B', 'MacNaughton, M R']",,,,
,PMC,Antibody-dependent cell-mediated cytotoxicity and spontaneous cell-mediated cytotoxicity against cells infected with porcine transmissible gastroenteritis virus.,,PMC1235942,,,"The objective of this study was to determine whether porcine peripheral blood leukocytes and intestinal intraepithelial leukocytes can mediate antibody-dependent cell-mediated cytotoxicity and spontaneous cell-mediated cytotoxicity against target cells infected with transmissible gastroenteritis virus. Peripheral blood leukocytes collected from six young adult pigs and intraepithelial leukocytes from a further five pigs were used as effector cells in chromium release assays against PK-15 cells persistently infected with transmissible gastroenteritis virus. Both peripheral blood leukocytes and intraepithelial leukocytes were capable of mediating antibody-dependent cell-mediated cytotoxicity and spontaneous cell-mediated cytotoxicity against PK-15 transmissible gastroenteritis cells. While the peripheral blood leukocytes mediated lower levels of specific 51Cr release in spontaneous cell-mediated cytotoxicity than in antibody-dependent cell-mediated cytotoxicity, the intraepithelial leukocytes were more effective in spontaneous cell-mediated cytotoxicity than antibody-dependent cell-mediated cytotoxicity.",,"['Cepica, A', 'Derbyshire, J B']",,,,
,PMC,Detection of antibodies to human coronaviruses 229E and OC43 in the sera of multiple sclerosis patients and normal subjects.,,PMC264797,,,Sera collected from 90 multiple sclerosis patients and 148 age-matched normal subjects were examined for the presence of antibodies against human coronaviruses (HCV) 229E and OC43 by enzyme immunoassay (EIA). The results demonstrated no significant difference between the MS patients and the normal subjects in their antibody titer to HCV 229E and HCV OC43. Further analysis of these 238 sera indicated that a stronger EIA reaction was generally observed against HCV OC43 (mean EIA value at an optical density of 492 nm = 0.896) than against HCV 229E (mean EIA value at an optical density of 492 nm = 0.346).,,"['Hovanec, D L', 'Flanagan, T D']",,,,
,PMC,Serological comparison of canine rotavirus with various simian and human rotaviruses by plaque reduction neutralization and hemagglutination inhibition tests.,,PMC264758,,,"By the plaque reduction neutralization test, the CU-1 strain of canine rotavirus was similar, if not identical, to three strains (no. 14, no. 15, and P) of the tentatively designated third human rotavirus serotype. In addition, strain CU-1 demonstrated a one-way antigenic relationship with two other strains (M and B) of the third human rotavirus serotype. The CU-1 strain of canine rotavirus hemagglutinated human group O, rhesus monkey, dog, sheep, and guinea pig erythrocytes. A two-way antigenic relationship between canine (CU-1) and simian (MMU 18006 and SA11) rotaviruses demonstrated previously by the plaque reduction neutralization test was confirmed further with two additional isolates (A79-10 and LSU 79C-36) of canine rotavirus by the plaque reduction neutralization test and the hemagglutination inhibition test. The CU-1 strain of canine rotavirus, which is known to be distinct from two well-characterized human rotavirus serotypes (Wa and DS-1), was also found to be distinct from the St. Thomas no. 4 strain, which is a newly defined fourth human rotavirus serotype. Thus, this canine strain, which is related antigenically to one of four human rotavirus serotypes, is another example of an animal rotavirus which shares serotype specificity with a human rotavirus.",,"['Hoshino, Y', 'Wyatt, R G', 'Greenberg, H B', 'Kalica, A R', 'Flores, J', 'Kapikian, A Z']",,,,
,PMC,Comparison of different antigen preparations as substrates for use in passive hemagglutination and enzyme-linked immunosorbent assays for detection of antibody against bovine enteric coronavirus.,,PMC270758,,,"Purified coronavirus, detergent extracts of purified coronavirus, and virus-infected Madin-Darby bovine kidney cells were evaluated as antigen substrates in enzyme-linked immunosorbent assay (ELISA) and passive hemagglutination systems. Only detergent-extracted and -unextracted, purified viruses were reactive as antigen substrates in ELISA, whereas all three antigen preparations could be used for sensitization of erythrocytes in the passive hemagglutination assay. The passive hemagglutination system with infected cell extracts exhibited a similar level of sensitivity and specificity to the ELISA system employing purified coronavirus but enabled 300 times more tests to be performed per volume of virus-infected cell culture.",,"['Crouch, C F', 'Raybould, T J']",,,,
,PMC,PARENTAL ORIGIN OF CHROMOSOME 15 DELETION IN PRADER-WILLI SYNDROME,,PMC5510872,,,,,"['Butler, Merlin G.', 'Palmer, Catherine G.']",,,,
,PMC,Mouse hepatitis virus type 4 infection of primary glial cultures from genetically susceptible and resistant mice.,,PMC348176,,,"Mouse hepatitis virus type 4 infection of primary glial cultures, which consisted principally of astrocytes (marked by glial fibrillary acidic protein) from encephalitis-susceptible BALB/c or F1 (BALB/c x SJL/J) hybrid mice and resistant SJL/J mice, was studied. Primary neuron cultures from BALB/c and F1 hybrid mice were previously shown to be permissive and were destroyed within 5 days by infection with mouse hepatitis virus type 4, whereas neurons from SJL/J mice were fully resistant. In contrast, in the present study a chronic infection was established and maintained for up to 18 days in glial cultures from all three mouse strains. Infected SJL/J mouse glial cultures produced 10- to 50-fold less infectious virus and showed less cytopathic effect than did cultures from either infected BALB/c or F1 hybrid mice. Cytopathic effect was evident initially in cells from all three strains, and continued virus production occurred in the presence of limited additional cytopathic effect. These results were not due to the production of detectable levels of interferon. This study showed that SJL/J mouse primary glial cultures were permissive for mouse hepatitis virus type 4 infection whereas SJL/J primary neuron cultures were not, and that there was an early lytic phase of infection followed by chronic infection in all three strains.",,"['Collins, A R', 'Tunison, L A', 'Knobler, R L']",,,,
,PMC,Presence of leader sequences in the mRNA of mouse hepatitis virus.,,PMC256579,,,"To determine the structure and the mechanism of synthesis of mouse hepatitis virus mRNA, the map positions of the large RNase T1-resistant oligonucleotides of the seven mouse hepatitis virus strain A59 intracellular mRNA species were studied. We found that all but one of the oligonucleotides were mapped at the positions within each mRNA consistent with the nested-set, stairlike structure of mouse hepatitis virus mRNA (Lai et al., J. Virol. 39:823-834). However, one oligonucleotide, 10, was mapped near the 5' ends of every mRNA and virion genomic RNA. In other words, oligonucleotide 10 and, therefore, the sequences around the 5' ends of the mRNAs are not colinear with the genomic sequences. Because this oligonucleotide is present only once in the genomic RNA, this result indicates that oligonucleotide 10 is not transcribed from multiple sites on the genomic template, but rather represents a leader RNA sequence which is joined to the body sequences of the different mRNAs during mRNA transcription. This provides the most direct evidence thus far for the presence of leader sequences in the mRNAs of mouse hepatitis virus, which is a cytoplasmic virus. Several possible mechanisms of RNA synthesis are discussed.",,"['Lai, M M', 'Patton, C D', 'Baric, R S', 'Stohlman, S A']",,,,
,PMC,Intrathecal antibody synthesis to virus antigens in multiple sclerosis.,,PMC1535858,,,"Intrathecal antibody synthesis against 17 common viruses and Mycoplasma pneumoniae lipid antigen was measured in 30 multiple sclerosis patients and 30 patients with other neurological diseases. Antibody synthesis was found against all of the antigens in at least a few of the MS patients. The highest number of patients had intrathecal synthesis of antibodies to measles, rubella and paramyxo type viruses and the lowest frequency was against M. pneumoniae, herpes simplex virus, adenovirus and cytomegalovirus antigens. Simultaneous antibody synthesis occurred against 1-11 different antigens in these patients. When the summation of different antibody specificities synthesized intrathecally was compared to the CSF-IgG Index, which measures the intrathecal immunoglobulin G synthesis, a fairly close correlation was found. The control patients had occasional antibody synthesis but generally only against one single virus antigen. The intrathecal antibody synthesis against viruses did not correlate to the disability of the MS patients. The intrathecal antibody synthesis was not different in younger and older patients or patients with shorter or longer disease duration, suggesting that events leading to intrathecal antibody synthesis may occur relatively early in life in these patients. When presence of Dw2 antigen was compared to different specificities of intrathecally synthesized immunoglobulins, only measles virus antibody synthesis showed correlation.",,"['Salmi, A', 'Reunanen, M', 'Ilonen, J', 'Panelius, M']",,,,
,PMC,"Response of mink, skunk, red fox and raccoon to inoculation with mink virus enteritis, feline panleukopenia and canine parvovirus and prevalence of antibody to parvovirus in wild carnivores in Ontario.",,PMC1235916,,,"Mink virus enteritis, feline panleukopenia and canine parvovirus-2 were inoculated separately into groups of raccoon, mink, red fox and striped skunk. Raccoons were highly susceptible to mink virus enteritis and feline panleukopenia, with animals developing clinical illness, and several dying within six to ten days of inoculation with lesions typical of parvovirus infection. Both viruses were shed in high titre in the feces of infected raccoons, and high antibody titres were stimulated. Raccoons inoculated with canine parvovirus-2 showed no signs; shedding of virus was sporadic though moderate titres of antibody developed. Mink inoculated with mink virus enteritis and feline panleukopenia developed signs and lesions of early parvovirus infection. No signs or significant lesions followed canine parvovirus-2 inoculation. Shedding of virus was heavy (mink virus enteritis) or sporadic (feline panleukopenia and canine parvovirus-2), though good serological responses were elicited to all three viruses. Red fox showed no signs of infection, shed all three viruses only sporadically, and the serological response was strong only to feline panleukopenia. Skunks developed low antibody titres, but no signs, and did not shed virus. Antibody to parvovirus was found in 79.2% of 144 wild red foxes; 22.3% of 112 wild raccoons; 1.3% of 157 wild skunks and 6/7 coyotes in southern Ontario. The likely significance of these viruses to wild and captive individuals and populations of these carnivores is discussed.",,"['Barker, I K', 'Povey, R C', 'Voigt, D R']",,,,
,PMC,Glycosylation of herpes simplex virus type 1 gC in the presence of tunicamycin.,,PMC255122,,,"The presence of O-glycosidic linkages on herpes simplex virus type 1 (HSV-1) glycoproteins was indicated by the synthesis and glycosylation of HSV-1 glycoproteins in the presence of tunicamycin. Monospecific antiserum to HSV-1 gC immunoprecipitated a 92,000-molecular-weight protein synthesized in the presence of tunicamycin and isotopically labeled with glucosamine or galactose. Anti-gAB did not immunoprecipitate a carbohydrate-labeled HSV-1 protein synthesized in the presence of tunicamycin. The purified glucosamine-labeled 92,000-molecular-weight protein synthesized in the presence of tunicamycin and the fully glycosylated forms of gAB and gC were tested for their sensitivity to mild alkaline hydrolysis. Purified gAB was resistant to mild alkaline hydrolysis, whereas gC and the 92,000-molecular-weight protein were both sensitive to mild alkaline hydrolysis. These results suggest that O-glycosidic linkages are associated with the HSV-1 gC glycoprotein.",,"['Wenske, E A', 'Courtney, R J']",,,,
,PMC,Neurovirulence of murine coronavirus JHM temperature-sensitive mutants in rats.,,PMC348101,,,"The murine coronavirus strain JHM is highly neurotropic in rats and has a marked tendency to cause demyelinating central nervous system diseases after intracerebral inoculation. The clinical diseases observed range from an acute encephalomyelitis occurring within 2 weeks postinfection to a subacute demyelinating encephalomyelitis developing several weeks or months postinfection. Uncloned wild-type virus induced both acute and subacute diseases, whereas cloned JHM virus grown in tissue culture caused only acute disease without the pronounced lesions of primary demyelination. In contrast, temperature-sensitive mutants selected from that clone were capable of inducing subacute demyelinating encephalomyelitis after prolonged incubation times. Viruses recovered from diseased animals were still temperature sensitive. Inoculation of temperature-sensitive mutants into suckling rats (age, 10 to 15 days) produced high rates of subacute demyelinating diseases running a more chronic course; these diseases often were not fatal. Those rats which did not show clinical signs frequently revealed inflammatory demyelinating lesions. These findings indicate that the rate and type of clinical disease are dependent on the neurovirulence of the virus mutant used for inoculation and the age of the animals at the time of infection.",,"['Wege, H', 'Koga, M', 'Watanabe, R', 'Nagashima, K', 'ter Meulen, V']",,,,
,PMC,Sequence of the nucleocapsid gene from murine coronavirus MHV-A59.,,PMC325759,,,"The nucleotide sequence of the RNA encoding the nucleocapsid protein of coronavirus MHV-A59 has been determined. Copy DNA was prepared from mRNA isolated from virally infected cells, fragmented and cloned in the phage vector M13 mp8 for direct sequence determination. A sequence of 1817 nucleotides, adjacent to the viral poly-A tail, was obtained. It contains a single long open reading frame encoding a protein of mol. wt. 49660, which is enriched in basic residues.",,"['Armstrong, J', 'Smeekens, S', 'Rottier, P']",,,,
,PMC,Replication of Mouse Hepatitis Viruses with High and Low Virulence in Cultured Hepatocytes,,PMC348038,,,"Ten strains of mouse hepatitis virus with different levels of virulence and hepatotropism were examined for the ability to replicate in cultured mouse hepatocytes. All of these viruses multiplied well in hepatocytes, attaining a maximum of 10(5) to 10(7) PFU per 0.2 ml, with cytopathic effects characterized by the formation of polykaryocytes. However, in nonparenchymal adherent cells of the liver (liver macrophages), highly virulent mouse hepatitis virus type 2 multiplied to a titer 1,000 times higher than that of mouse hepatitis virus S with a low virulence. These results suggest that the virulence of mouse hepatitis virus in infected mice is determined by its potential for replication not in hepatocytes, but in macrophages, including Kupffer cells in the liver.",,"['Taguchi, Fumihiro', 'Kawamura, Seiji', 'Fujiwara, Kosaku']",,,,
,PMC,Potential spectrum of etiological agents of viral enteritis in hospitalized infants.,,PMC272636,,,"Fecal specimens were obtained from 1,160 infants and young children with acute nonbacterial gastroenteritis over a period of 2 years. A total of 100 specimens were obtained from age-matched asymptomatic controls. The specimens were examined for the presence of viruses by electron microscopy. Viruses or virus-like particles frequently associated with enteritis were detected in 27% (314 of 1,160) of the symptomatic patients. No viruses or virus-like particles were detected in the 100 control subjects. Rotavirus was detected in 73% (230 of 314) of the virus-positive samples. The mean age of rotavirus-positive patients was 11.5 months, although the patients ranged in age from 2 weeks to 5 years. Of the symptomatic patients, 45 (14%) exhibited small virus-like particles (15 to 40 nm) in the feces in the absence of any other detectable pathogen. Some of the virus-like particles observed in these patients appeared to be similar to astrovirus, and some appeared to be similar to the Otofuke agent or possibly minireovirus. Significantly, however, the mean age of infants with enteritis from whom these small virus-like particles were recovered was 4.5 months (range, 10 days to 19 months). Our findings confirmed the already-known fact that rotaviruses constitute the most important cause of viral enteritis in young children. In addition, small viruses may be an important cause of gastroenteritis in infants under 5 months of age.",,"['Riepenhoff-Talty, M', 'Saif, L J', 'Barrett, H J', 'Suzuki, H', 'Ogra, P L']",,,,
,PMC,"Evaluation of a computer-assisted, kinetics-based enzyme-linked immunosorbent assay for detection of coronavirus antibodies in cats.",,PMC272610,,,"A computer-assisted, kinetics-based enzyme-linked immunosorbent assay was adapted for the detection of coronavirus antibodies in feline serum. An alkaline antigen diluent (carbonate-bicarbonate buffer, pH 9.6) used in initial experiments produced diffuse, nonspecific color reactions in both viral and control antigen cuvettes which were correlated, paradoxically, with coronavirus antibody levels in test sera. These interfering reactions were minimized by use of lower-pH antigen diluents such as water and phosphate-buffered saline. Background kinetics-based enzyme-linked immunosorbent assay reactivity directed against a noncoronaviral component of antigen tissue culture fluids could then detected in numerous sera, particularly in samples with lower titers. Much of this reactivity was shown to be associated with bovine gamma globulins in cell culture fluid. It was not serum lot or species specific, since a variety of bovine serum lots as well as individual lots of serum from other mammalian and avian species reacted. Reactivity was markedly reduced when cells for antigen preparation were grown in gamma globulin-free bovine serum. Generation of corrected slope values from the kinetics-based enzyme-linked immunosorbent assay made it possible to correct for residual background reactivity in individual test sera and thus eliminate a potentially major source of false-positive reactions. Collectively, these studies indicated that the control of nonspecific reactivity in feline coronavirus serology is absolutely essential to obtain useful estimates of specific antibody responses.",,"['Barlough, J E', 'Jacobson, R H', 'Downing, D R', 'Marcella, K L', 'Lynch, T J', 'Scott, F W']",,,,
,PMC,"Virus-like particles, 45 to 65 nm, in intestinal contents of neonatal calves.",,PMC1235895,,,"Enveloped virus particles 45 to 65 nm in diameter, tentatively called minicorona virus, were detected by electron microscopy in the intestinal contents of one normal and seven diarrheic calves in Quebec dairy herds. The agent was shown to be antigenically unrelated to the Nebraska calf diarrhea coronavirus and to the bovine viral diarrhea virus by counterimmunoelectrophoresis and fluorescent-antibody techniques. Antibodies against these particles were demonstrated in the serum of affected calves using immunoelectron microscopy. The agent could not be isolated in cell cultures and its possible role as etiological agent in calf diarrhea is still to be determined.",,"['Dea, S', 'Roy, R S', 'Elazhary, M A']",,,,
,PMC,Neonatal Diarrhea of Pigs in Quebec: Infectious Causes of Significant Outbreaks,,PMC1235876,,,"To evaluate the relative importance of the various enteropathogens causing neonatal diarrhea in Quebec farrowing operations, observations were made on 749 diarrheic pigs from 325 outbreaks of diarrhea. They were one to 15 days of age, and were obtained alive for necropsy generally within 48 hours of the onset of diarrhea. Some pigs were from severe, explosive outbreaks of diarrhea with high morbidity and mortality rates, while others were from herds with chronic neonatal diarrhea with lower morbidity and mortality rates. A combination of bacteriological, virological and histological methods were used to study the pigs. Viruses were incriminated in 60%, bacteria in 23% and coccidia in 15.3% of the 325 diarrhea outbreaks. Transmissible gastroenteritis virus was by far the most common enteropathogen with a prevalence of 52%; rotavirus was implicated in 9.2% of the outbreaks while adenovirus was incriminated in 0.30% of the outbreaks. Enterotoxigenic Escherichia coli were involved in 22.4% of the cases while Clostridium perfringens type C was an occasional finding. Coccidia involved in our herds were identified as Isospora suis. The disease was attributed to infection with a single etiologic agent in 590 diarrheic pigs (78%) while combinations of agents were present in only 90 (12%). The age-specific occurrence of the various enteropathogens was evaluated. Transmissible gastroenteritis virus was the most common enteropathogen in all age groups. Colibacillosis was common in pigs which became diarrheic under five days of age; in this age group, the enterotoxigenic E. coli were frequently found alone, but were usually combined with other agents in older pigs. The prevalence of coccidia was high in pigs which became diarrheic between five and 15 days of age. Rotavirus infection was common in diarrheic pigs older than ten days of age. Although individual baby pigs were commonly infected with a single enteropathogen, it was very common to see more than one agent involved in an outbreak of diarrhea, particularly when pigs of different ages were affected. Observations on the occurrence of the enteropathogens according to the seasons were also made. Occurrence of transmissible gastroenteritis was throughout the year with the highest prevalence during the fall, winter and spring months. Colibacillosis and coccidiosis were more common in the summer, fall and early winter months with the lowest prevalence in the spring months.",,"['Morin, M.', 'Turgeon, D.', 'Jolette, J.', 'Robinson, Y.', 'Phaneuf, J.B.', 'Sauvageau, R.', 'Beauregard, M.', 'Teuscher, E.', 'Higgins, R.', 'Larivìere, S.']",,,,
,PMC,Coronavirus mRNA synthesis involves fusion of non-contiguous sequences.,,PMC555368,,,Positive-stranded genomic RNA of coronavirus MHV and its six subgenomic mRNAs are synthesized in the cytoplasm of the host cell. The mRNAs are composed of leader and body sequences which are non-contiguous on the genome and are fused together in the cytoplasm by a mechanism which appears to involve an unusual and specific 'polymerase jumping' event.,,"['Spaan, W', 'Delius, H', 'Skinner, M', 'Armstrong, J', 'Rottier, P', 'Smeekens, S', 'van der Zeijst, B A', 'Siddell, S G']",,,,
,PMC,"Cryptosporidiosis in man, domestic animals and birds: a review.",,PMC1438565,,,,,"Angus, K W",,,,
,PMC,Primary peritonitis in children and adults.,,PMC2417367,,,"Five cases of primary peritonitis are presented, with a sixth related case of pneumococcal peritonitis secondary to a ruptured ovarian cyst. The patients comprised 4 young girls who recovered, and 2 elderly females who died. Pneumococci were isolated in 3 patients; no organism was found in the other 3. One case of primary measles peritonitis has no apparent precedent.",,"['Armitage, T. G.', 'Williamson, R. C.']",,,,
,PMC,Bovine Cryptosporidiosis: Clinical and Pathological Findings in Forty-two Scouring Neonatal Calves,,PMC1790278,,,"Cryptosporidia organisms were identified in 42 of 161 (26%) neonatal, diarrheic calves, over a 32 month period commencing July 1979. Forty of the 161 calves were submitted alive and cryptosporidiosis was diagnosed in 63% (25 of 40) of them. The cryptosporidia infected calves were usually one to two weeks old and came from 26 herds where the typical history was profuse, watery diarrhea in nearly all neonatal calves. The diarrhea usually started around one week of age, was unresponsive to all conventional antidiarrhea therapies, lasted for two or more weeks and was usually fatal. Twenty-nine (69%) of the cryptosporidia infected calves were submitted between December and February. These calves were often hutch reared. Histopatholoical examination revealed large numbers of the coccidial parasite Cryptosporidium sp embedded in the microvilli of jejunal and ileal absorptive enterocytes of all affected calves. The organisms were identified as trophozoites and schizonts (asexual stages) and macrogametes (female sexual stages) with the electron microscope. Microgametes (male sexual stages) were not identified. Occasionally a merozoite (asexual stage) was also seen apparently burrowing into or about to be enveloped by a host microvillus. Observation of the organisms was much easier when diarrheic calves were submitted alive. Enterotoxigenic Escherichia coli were often cultured from intestines of dead calves and occasionally from calves submitted alive. Coronavirus particles were seen in one calf. In the last year of this study, oocysts were identified in fecal smears stained with May-Grünwald-Giemsa stain and fecal samples using a dichromate solution flotation technique.",,"['Sanford, S. E.', 'Josephson, G. K. A.']",,,,
,PMC,Coronavirus proteins: structure and function of the oligosaccharides of the avian infectious bronchitis virus glycoproteins.,,PMC256337,,,"The recent finding that the E1 glycoproteins of murine coronaviruses contain only O-linked oligosaccharides suggested that this unusual modification might be a distinguishing feature of coronaviruses and might play an essential role in the life cycle of this family of viruses. To examine these possibilities, we analyzed the oligosaccharide moieties of the membrane proteins of the avian coronavirus infectious bronchitis virus. In addition, we determined the effect of inhibiting the glycosylation of these proteins on viral maturation and infectivity. Infectious bronchitis virus virions contain nine proteins. Four of these proteins, GP36, GP31, GP28, and P23, are closely related structurally and appear to be homologous to the E1 proteins of murine coronaviruses. We found that the oligosaccharides of GP31 and GP28 could be removed with endoglycosidase H and that neither of these glycoproteins was detectable in tunicamycin-treated cells. These two results indicated that GP31 and GP28 contain N-linked oligosaccharides. Therefore, O-linked oligosaccharides are not a universal feature of the small coronavirus membrane glycoproteins. Tunicamycin inhibited glycosylation of all of the viral glycoproteins but did not inhibit production of virions by infectious bronchitis virus-infected cells. The virions released by these cells contained only the three non-glycosylated viral proteins P51, P23, and P14. These particles were not infectious. Therefore, it appears that glycosylated infectious bronchitis virus polypeptides are not required for particle formation. However, the viral glycoproteins are apparently indispensible for viral infectivity.",,"['Stern, D F', 'Sefton, B M']",,,,
,PMC,Coronavirus proteins: biogenesis of avian infectious bronchitis virus virion proteins.,,PMC256336,,,"We examined the synthesis of viral structural proteins in cultured cells infected with the avian coronavirus infectious bronchitis virus. Tryptic peptide mapping was used to determine the structural relationships of the intracellular proteins to the virion polypeptides. Pulse-chase experiments were performed to identify precursors to the virus-specific proteins. We found that the nucleocapsid protein, P51, and the small viral membrane proteins GP31, GP28, and P23 do not undergo post-translational proteolytic processing. In contrast, GP90 and GP84, the two large virion membrane proteins, were found to be produced by cleavage of a single precursor, GP155. This demonstrated that at least one coronavirus mRNA specifies two virion proteins.",,"['Stern, D F', 'Sefton, B M']",,,,
,PMC,Papovaviral persistent infections.,,PMC281554,,,,,"Norkin, L C",,,,
,PMC,Selected mutants of mouse hepatitis virus type 4 (JHM strain) induce different CNS diseases. Pathobiology of disease induced by wild type and mutants ts8 and ts15 in BALB/c and SJL/J mice.,,PMC1916093,,,"The model system of central nervous system (CNS) disease induced by mouse hepatitis virus type 4 (MHV-4) is explored by comparison of wild type (wt) MHV-4 and two temperature-sensitive (ts) mutants, designated ts8 and ts15, in BALB/c and SJL/J mice. In BALB/c mice, 3 plaque-forming units (PFU) of wt MHV-4 given intracerebrally caused fatal encephalomyelitis in all mice by 7 days after infection, with spread of virus outside the CNS, especially to liver. In SJL/J mice, 3 PFU of wt virus was cleared within 2-3 days, with little spread, and up tp 100 PFU failed to cause fatal encephalomyelitis. However, larger amounts of virus, like 1000 PFU, caused fatal encephalomyelitis in SJL/J mice. In contrast, 10(4) PFU of MHV-4 ts8 did not cause death in either BALB/c or SJL/J mice, and persisted in the CNS of both strains while retaining its ts phenotype. There was significatnly less spread of virus outside the CNS. BALB/c mice usually showed demyelination, remyelination, and recurrent demyelination with ts8, while SJL/J mice only rarely had lesions. Intracerebral inoculation with 10(4) PFU of MHV-4 ts15 was associated with a persistent infection in CNS and liver of BALB/c mice; however, only occasional demyelination and hepatic lesions occurred. TS15 did not cause death in either BALB/c or SJL/J mice and did not cause histopathologic injury in SJL/J mice.",,"['Knobler, R. L.', 'Tunison, L. A.', 'Lampert, P. W.', 'Oldstone, M. B.']",,,,
,PMC,Experimental cryptosporidiosis in laboratory mice.,,PMC347763,,,"Eight strains of laboratory mice were susceptible to subclinical infections with Cryptosporidium sp. at 1 to 4 days of age, but only a transient infection could be established at 21 days of age or older. Immunosuppression of 21-day-old mice failed to render them more susceptible to infection. Laboratory storage conditions for Cryptosporidium sp. were investigated by titration in 1- to 4-day-old mice. Storage by freezing with a variety of cryoprotectants was unsuccessful, but storage at 4 degrees C in phosphate-buffered saline or 2.5% potassium dichromate was possible for 4 to 6 months.",,"['Sherwood, D', 'Angus, K W', 'Snodgrass, D R', 'Tzipori, S']",,,,
,PMC,Occurrence and frequency of coronavirus infections in humans as determined by enzyme-linked immunosorbent assay.,,PMC347755,,,"The occurrence of human coronavirus (HCV) infections was analyzed by using sequential sera taken between 1976 and 1981 from adults working in the London area. Antibody rises to HCV 229E and HCV OC43 group viruses were measured in serum samples from these subjects by enzyme-linked immunosorbent assay. HCV infections were found throughout the year, although most occurred during two periods, from June through September and from December through February. There were no marked seasonal differences in either the range of antibody rises obtained or in the HCV groups to which these antibody rises were directed. However, there were more HCV antibody rises during the summer than in the winter. The antibody duration varied considerably, but had a mean of 3.5 months. Finally, the frequency of HCV infection per person was calculated to be 1 per 7.8 months.",,"Macnaughton, M R",,,,
,PMC,Immunity to rotavirus in conventional neonatal calves.,,PMC272505,,,"The local and systemic humoral immune responses to rotavirus were studied in six conventional neonatal calves. Attenuated bovine rotavirus was administered either orally or directly into an isolated intestinal loop. The parameters monitored were neutralizing rotavirus antibody in serum, immunofluorescent and neutralizing rotavirus antibody in intestinal loop washings, and rotavirus antibody-producing cells in intestinal mucosa. An antibody response was observed in the serum and intestinal secretions from one calf only. Viral replication was not detected in the isolated intestinal loop. Rotavirus antibody-producing cells were found in the intestinal mucosa of five calves. Double staining revealed that most of these cells produced antibody of the immunoglobulin A class. The conclusions were: (i) a previously described system to detect rotavirus antibody-producing cells can be used to study immune responses in neonatal calves, (ii) the class or subclass of antibody in rotavirus antibody-producing cells can be determined by double immunofluorescent staining, (iii) neonatal calves respond to rotavirus inoculation with a local immunoglobulin A response, and (iv) most of the rotavirus antibody-producing cells are located in the mucosa of the proximal small intestine.",,"['Vonderfecht, S L', 'Osburn, B I']",,,,
,PMC,Replication of mouse hepatitis virus: negative-stranded RNA and replicative form RNA are of genome length.,,PMC256291,,,"There are seven virus-specific mRNA species in mouse hepatitis virus-infected cells (Lai et al., J. Virol. 39:823-834, 1981). In this study, we examined virus-specific negative-stranded RNA to determine whether there are corresponding multiple negative-stranded RNAs. Intracellular RNA from mouse hepatitis virus-infected cells was separated by agarose gel electrophoresis, transferred to nitrocellulose membranes, and hybridized to positive-stranded genomic 60S [32P]RNA. Only a single RNA species of genomic size was detected under these conditions. This RNA was negative stranded. No negative-stranded subgenomic RNA was detected. We also studied double-stranded replicative-form RNA in the infected cells. Only one replicative-form of genomic size was detected. When the double-stranded RNA isolated without RNase treatment was analyzed, again only one RNA species of genomic size was detectable. Furthermore, most of the virus-specific mRNAs could be released from this RNA species upon heating. These results suggest that all of the mouse hepatitis virus-specific RNAs are transcribed from a single species of negative-stranded RNA template of genomic size.",,"['Lai, M M', 'Patton, C D', 'Stohlman, S A']",,,,
,PMC,"Activity of 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (MDL-860) against picornaviruses in vitro.",,PMC183806,,,"The newly synthesized compound 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (MDL-860) has been found to inhibit picornavirus replication. In multiple growth cycle experiments, 1 microgram of MDL-860 per ml caused a reduction in virus yield of at least 1.0 log10 50% tissue culture infectious doses per 0.2 ml for 8 of 10 enteroviruses and 72 of 90 rhinovirus serotypes. This antiviral activity was dependent on both compound concentration and virus inoculum size. At concentrations that had no toxic effects on cell cultures, MDL-860 did not inhibit cytopathic effect or hemadsorption activity due to coronavirus 229-E, vesicular stomatitis virus, herpes simplex virus type 1, adenovirus, influenza virus A, or parainfluenza virus 1. Compound concentrations up to 25 micrograms/ml did not cause cytopathic effect in short-term cultures of rhesus monkey, WI-38, or HeLa cells; 10 micrograms/ml did not inhibit the replication of HeLa cells. The mechanism of action of MDL-860 has not been defined, although it was not directly virucidal and appeared to inhibit picornaviruses specifically at an early step in the virus-host cell interaction.",,"['Powers, R D', 'Gwaltney, J M', 'Hayden, F G']",,,,
,PMC,The postnatal acquisition of factors which affect the influenza haemagglutination-inhibition test.,,PMC2134217,,,"Levels of maternally transferred antibodies against the surface antigen of the A/Texas/1/77 strain of influenza virus showed the expected decline during infancy when measured by complement fixation (CF). However, this decline was not observed when these antibodies were measured by haemagglutination-inhibition (HI). It has been postulated that this discrepancy is due to the acquisition, in the early days of life, of non-specific serum factors which increase the HI activity of sera. The levels of these factors were determined indirectly by calculating HI:CF ratios and it was shown that the factors are rapidly acquired by children between the fifth and twentieth week of life.",,"['Grint, P. C.', 'Argent, S.', 'Heath, R. B.']",,,,
,PMC,Antibody against viruses in maternal and cord sera: specific antibody is concentrated on the fetal side of the circulation.,,PMC2134211,,,"Paired maternal and cord sera from 100 pregnancies were tested for antibodies against herpes simplex virus, measles virus and respiratory syncytial virus by complement fixation and for antibodies against rubella virus, influenza A virus and influenza B virus by haemagglutination-inhibition. For four viruses (herpes simplex, measles, respiratory syncytial and rubella) higher levels of antibody were found in cord than in maternal sera. There was no difference between maternal and cord serum titres against influenza B virus but significantly higher levels of antibody against influenza A virus were found in maternal sera than in cord sera. This discrepancy was investigated by measuring antibodies against the surface antigens of influenza A by a complement fixation technique, and by single radial haemolysis. Both methods showed a preponderance of virus-specific antibody in cord sera. We conclude that IgG antibodies against most, if not all, viruses are concentrated on the fetal side of the circulation, but the conventional haemagglutination-inhibition techniques may fail to detect this difference.",,"['Griffiths, P. D.', 'Berney, S. I.', 'Argent, S.', 'Heath, R. B.']",,,,
,PMC,Diet of Racing Sled Dogs Affects Erythrocyte Depression by Stress,,PMC1790196,,,"Fourteen racing huskies were matched into pairs then assigned to two diets, a commercial stress diet and an experimental diet. Proportions of protein: fat:carbohydrate on an available energy basis were 23:57:20 in a commercial stress diet and 28:69:3 in an experimental diet. The team participated in the 1979 Iditarod Trail race and was overtaken by an episode of diarrhea. Clinical signs were suggestive of parvovirus infection; high serum titers of parvo antibodies were found after the race. Blood examination showed normal levels of metabolites, electrolytes and enzymes after the race. Erythrocyte counts were depressed significantly during the race, by 15% in dogs fed an experimental diet and by 27% in those fed a commercial stress diet. Erythrocyte parameters have also become depressed during the racing season in middle distance sled dogs fed 28% protein (energy basis) but not 32 or 39%. Depressed red blood cell production has been demonstrated previously in dogs subjected to stress induced experimentally in several ways, and its restoration has been affected by dietary protein. Erythrocyte parameters may be useful indicies of the degree of stress in a dog as well as the adequacy of its protein intake during stress.",,"['Adkins, T. O.', 'Kronfeld, D. S.']",,,,
,PMC,In Vivo and In Vitro Models of Demyelinating Disease: Endogenous Factors Influencing Demyelinating Disease Caused by Mouse Hepatitis Virus in Rats and Mice,,PMC347672,,,"Intracerebral inoculation of JHM virus (JHMV), the neuropathic strain of mouse hepatitis virus, into Wistar Furth, Wistar Lewis, and Fischer 344 rats at various ages indicated that Wistar Furth rats are more susceptible to the virus than are the other strains. Fischer 344 and Wistar Lewis rats were more resistant to inoculation at 2 and 5 days of age and completely resistant by 10 days of age. In contrast, Wistar Furth rats which were very susceptible at both 2 and 5 days of age remained susceptible until 21 days of age. Intracerebral challenge of an F1 cross between Wistar Furth and Wistar Lewis rats at 10 days of age indicated that resistance to JHMV infection is dominant. Cyclophosphamide treatment 28 days after intracerebral inoculation exacerbated an inapparent infection, leading to paralysis in eight of nine and death in six of nine Wistar Furth test rats. In such immunosuppressed animals, grey- and white-matter lesions were noted throughout the central nervous system, in contrast to the purely demyelinating lesions noted previously. Since rats, unlike mice, were not susceptible to disease after intracerebral injection with the serorelated viscerotropic strain MHV-3, we wished to extend our understanding of the neurological disease process elicited by the two viruses in rodents. For this reason, various mouse strains, including some with recognized immunodeficiencies, were challenged by different routes of inoculation. Intraperitoneal infection of nude and beige mice with JHMV indicated that lack of natural killer cell functions does not markedly enhance the susceptibility to virus, whereas T-cell activity appears to be essential for resisting infection. JHMV and MHV-3 replication in peritoneal macrophages from highly resistant A/J mice was reduced in comparison with that noted in macrophages from susceptible C57BL6/J mice. An initial intraperitoneal inoculation of JHMV was able to protect C57BL6/J mice against fatal intracerebral challenge within 3 days, whereas A/J mice remained susceptible beyond day 3. The protective effect did not appear to result from increased levels of circulating interferon, preceded elevation in serum JHMV-neutralizing antibody titers, and persisted for at least several weeks after intraperitoneal inoculation. Based on the combined studies described here and on previous work by us and others, it appears that the factors influencing the outcome of coronavirus disease in rodents are age at inoculation, route of challenge, genetic constitution of the virus and host, and competence of the immune system, particularly cellular immunity involving T-cells.",,"['Sorensen, O.', 'Dugre, R.', 'Percy, D.', 'Dales, S.']",,,,
,PMC,"Antigenic relationships among homologous structural polypeptides of porcine, feline, and canine coronaviruses.",,PMC347660,,,"Transmissible gastroenteritis virus of swine (TGEV), feline infectious peritonitis virus (FIPV), and canine coronavirus were studied with respect to their serological cross-reactivity in homologous and heterologous virus neutralization, immune precipitation of radiolabeled TGEV, electroblotting, and enzyme-linked immunosorbent assay using individual virion polypeptides prepared by polyacrylamide gel electrophoresis. TGEV was neutralized by feline anti-FIPV serum, and the reaction was potentiated by complement; heterologous neutralization involved antibody reacting with the peplomer protein (P), the envelope protein (E), and cellular (glycolipid) components incorporated into the TGEV membrane. Electrophoretic analysis of immune precipitates containing [35S]methionine-labeled disrupted TGEV and feline anti-FIPV antibody confirmed the reaction with the P and E polypeptides and showed the nucleocapsid protein (N) in addition. Electroblotting, followed by incubation with antibody, 125I-labeled protein A, and fluorography, disclosed cross-reactions between the three viruses at the N and E levels and revealed differences in the apparent molecular weights of the latter. Enzyme immunoassays performed with standard amounts of immobilized P, N, and E polypeptides of the three viruses showed recognition of the antigens by homologous and heterologous antibody to comparable degrees. These results indicate a close antigenic relationship between TGEV, FIPV, and canine coronavirus due to common determinants on the three major virion proteins. The taxonomic implications of these findings are discussed.",,"['Horzinek, M C', 'Lutz, H', 'Pedersen, N C']",,,,
,PMC,Kinetics of immunosuppression of sporozoite-induced immunity by Mycobacterium bovis BCG.,,PMC347641,,,"The data reported in this study demonstrate that the vaccination of NIH/Nmri mice with viable Mycobacterium bovis BCG organisms induces a state of immunosuppression that renders the recipient animals incapable of a protective immune response to the malaria sporozoite vaccine. The expression of this altered protective immune response is dependent upon the dosage of the two live vaccines, as well as upon the sequence of their administration. Data presented here show that the skin test responses (Arthus and delayed type) of BCG-vaccinated mice do not correlate with the suppression of sporozoite immunity. Evidence is also presented to support the hypothesis that the abrogated immune response to sporozoite vaccination induced by BCG is a result of a loss of immunological memory.",,"Smrkovski, L L",,,,
,PMC,Is progressive multifocal leukoencephalopathy a chronic disease because of defective interfering particles or temperature-sensitive mutants of JC virus?,,PMC256229,,,"JC virus was examined for temperature sensitivity and for evidence of defective interfering particles as a means of explaining the slow chronic nature of progressive multifocal leukoencephalopathy (PML). JC virus direct from the brain tissue of seven persons with PML was not temperature sensitive as indicated by in vitro assay at 37 and 39 degrees C. In fact, more cells contained viral antigen at 39 than at 37 degrees C. The amount of infectious virus also was increased at 39 degrees C. Virions isolated directly from diseased brain tissue had a higher buoyant density than did virus from the same PML patient passaged in culture and containing genomic deletions. In contrast to DNA from culture-passed virus, DNA extracted from virions direct from brain tissue was homogeneous in length. In 13 separate cases examined, the viral DNA direct from the brain was homogeneous although variations in length were noted among DNAs from different cases. Restriction enzyme cleavage patterns identified all as JC virus DNA. It was concluded that neither temperature sensitivity nor DI particles can be used to explain the slow, progressive nature of PML.",,"['Grinnell, B W', 'Martin, J D', 'Padgett, B L', 'Walker, D L']",,,,
,PMC,Cell-free translation of murine coronavirus RNA.,,PMC256201,,,"The coding assignments of the intracellular murine hepatitis virus-specific subgenomic RNA species and murine hepatitis virion RNA have been investigated by cell-free translation. The six murine hepatitis virus-specific subgenomic RNAs were partially purified by agarose gel electrophoresis and translated in an mRNA-dependent rabbit reticulocyte lysate, and the cell-free translation products were characterized by gel electrophoresis, immunoprecipitation, and tryptic peptide mapping. These studies have shown that RNA 7 codes for the nucleocapsid protein, RNA 6 codes for the E1 protein, RNA 3 codes for the E2 protein, and RNA 2 codes for a 35,000-dalton nonstructural protein. Genomic RNA directs the cell-free synthesis of three structurally related polypeptides of greater than 200,000 in molecular weight.",,"['Leibowitz, J L', 'Weiss, S R', 'Paavola, E', 'Bond, C W']",,,,
,PMC,Vaccination Guidelines for Dogs and Cats: 1982 Update,,PMC1790186,,,,,,,,,
,PMC,A Comparison of Dichromate Solution Floatation and Fecal Smears for Diagnosis of Cryptosporidiosis in Calves,,PMC1790179,,,"Fecal samples from eleven calves experimentally infected with cryptosporidia were examined by two methods to evaluate their sensitivity and ease of use as diagnostic techniques. Comparison of a dichromate solution floatation and fecal smear techniques indicated that the former method was more sensitive. Oocysts were detected in feces earlier and for a longer period following exposure, and were easier to visualize using the dichromate solution floatation procedure. In addition, the dichromate solution floatation technique eliminated Candida albicans which can sometimes be confused with cryptosporidial oocysts in fecal smears. Another advantage was that oocysts could readily be detected in fecal samples stored as long as 120 days in dichromate solution. Using the dichromate solution floatation technique, it was shown that shedding of cryptosporidial oocysts in feces occurred from two to 20 days after oral challenge but was not always accompanied by diarrhea. Infection with cryptosporidia was confirmed in two calves at necropsy. Calves which were not sacrificed for portmortem examination recovered without treatment. The dichromate solution floatation technique is simple, rapid, inexpensive and should facilitate detection of cryptosporidia by diagnostic laboratories and some veterinary practitioners.",,"['Willson, P. J.', 'Acres, S. D.']",,,,
,PMC,Passive immunity in calf diarrhea: vaccination with K99 antigen of enterotoxigenic Escherichia coli and rotavirus.,,PMC347573,,,"Twenty-four pregnant cows were vaccinated intramuscularly with K99 extract from enterotoxigenic Escherichia coli and inactivated rotavirus as follows: six cows were injected with 2 ml of oil-adjuvanted vaccine; six cows were injected with 0.5 ml of oil-adjuvanted vaccine; six cows were injected with 4 ml of aluminum hydroxide-adjuvanted vaccine twice with a four-week interval; and six cows were unvaccinated as controls. Calves born to these cows were challenged with enterotoxigenic E. coli at 6 to 18 h after birth. Serum and milk antibodies to K99 and rotavirus in cows vaccinated with either dose of oil vaccine were significantly increased until at least 28 days after calving. In cows vaccinated with alhydrogel vaccine, there was a significant K99 antibody increase in serum and in colostrum but not in milk and a significant rotavirus antibody increase only in colostrum. Five of six calves born to unvaccinated cows developed enterotoxic colibacillosis after challenge, and all excreted the challenge strain of enterotoxigenic E. coli. None of the 18 calves in the three vaccinated groups developed clinical colibacillosis, and fecal excretion of the challenge organism was reduced. A combined enterotoxigenic E. coli-rotavirus vaccine may prove useful in preventing some outbreaks of calf diarrhea.",,"['Snodgrass, D R', 'Nagy, L K', 'Sherwood, D', 'Campbell, I']",,,,
,PMC,"Potassium tartrate-glycerol as a density gradient substrate for separation of small, round viruses from human feces.",,PMC272364,,,"Cesium chloride density gradients are frequently used for virus concentration or purification in the preparation of human feces for examination by electron microscopy, Disruption of some of the fecal viruses occurs if they are pelleted from the density gradient in an additional concentration step. This report highlights an important limitation imposed by the use of cesium chloride as a density gradient substrate in attempting to recover small, round, virus-like particles from feces and suggests an alternative substrate which preserves virus morphology without the use of additional protective agents.",,"['Ashley, C R', 'Caul, E O']",,,,
,PMC,Occurrence of viruses in human stools in the Ahaggar (Alberia).,,PMC2134164,,,"From October 1977 to May 1980, 243 stools collected in sedentary and semi-nomadic populations of the Ahaggar (Algerian Sahara) were examined using immunoelectronmicroscopy and tissue culture inoculation. Immunoelectronmicroscopy revealed the presence of rotaviruses in 8, coronaviruses in 26, adenoviruses in 5 and small round viruses in 4. Enteroviruses were isolated in tissue culture from 24 stools. Rotaviruses were present in the Ahaggar but were associated with little acute enteric disease. The high frequency of coronaviruses both in gastroenteritis patients and in patients without disease was surprising. The prevalence of enteroviruses in this hyperarid zone was similar to or higher than that found in noticeably more human countries. Further systematic bacterial, viral and parasitic examinations are required to clarify the role of the above viruses in the aetiology of gastroenteritis in this region.",,"['Puel, J. M.', 'Orillac, M. S.', 'Bauriaud, R. M.', 'Boughermouh, R.', 'Akacem, O.', 'Lefevre-Witier, P.']",,,,
,PMC,Detection of adenoviruses in stools of children with nonbacterial gastroenteritis.,,PMC1863184,,,,,"['Blaskovic, P. J.', 'Freitag, R. M.', 'McLaughlin, B.']",,,,
,PMC,Detection by radioimmunoassay and enzyme-linked immunosorbent assay of coronavirus antibodies in bovine serum and lacteal secretions.,,PMC272290,,,"The sensitivity of a radioimmunoassay (RIA), an enzyme-linked immunosorbent assay (ELISA), and a serum neutralization assay (SN) for detecting antibodies to bovine coronavirus in serum and colostrum were compared. Although there proved to be a good correlation among all three assays (r = 0.915 and 0.964 for RIA with SN and ELISA, respectively), RIA and ELISA proved to be at least 10 times more sensitive than neutralization tests. By using these techniques, it was possible to detect a time-dependent decrease in antibody levels in bovine colostrum after parturition. Using ELISA, we demonstrated that 12 of 12 herds in Saskatchewan, and 109 of 110 animals tested, and antibody to bovine coronavirus. There was no elevated antibody response in serum or lacteal secretions of cows vaccinated once or twice with a commercially available modified live rota-coronavirus vaccine. In addition to being more sensitive than SN, ELISA and RIA proved to have other advantages for measuring antibody levels to bovine coronavirus and therefore warrant wider use as tools in diagnostic virology.",,"['Rodak, L', 'Babiuk, L A', 'Acres, S D']",,,,
,PMC,The bursa: Fabricius to Delaware.,,PMC1437916,,,,,"Cullen, G A",,,,
,PMC,Selective infection of lower respiratory tract by respiratory viruses in children with recurrent respiratory tract infections.,,PMC1498648,,,"Thirty preschool children presenting with recurrent respiratory infections and their unaffected siblings were observed prospectively for a year. The index children experienced more episodes of acute respiratory infection than their siblings. Respiratory viruses were the major cause of respiratory infections. The index children had lower respiratory tract disease, predominantly wheeze, during 34% of proved respiratory virus infections compared with 11% of such infections experienced by the control children (p less than 0.02). Atopic children had an increased tendency to wheeze that did not reach significance, but atopy was not associated with increased susceptibility to respiratory infections.",,"['Isaacs, D', 'Clarke, J R', 'Tyrrell, D A', 'Valman, H B']",,,,
,PMC,Interferon in rabbit sera after inoculation with Treponema pallidum suspensions contaminated with PED virus.,,PMC1046033,,,"Paired rabbits sera were examined for the presence of interferon and pathogenicity for rabbits. The sera were obtained before and 48 hours after inoculation with Treponema pallidum suspensions of rabbit origin in 12 selected laboratories. Classical interferon, detectable in dilutions from 1/9 to 1/81, were found in 27 out of 39 postinoculation sera from which the pleural effusion disease (PED) virus was isolated. Serum interferon was not detectable in dilutions greater than or equal to 1/9 in 16 virus-negative postinoculation sera or in any of the 55 preinoculation sera. Interferon was found more often in sera from which highly virulent strains of PED virus were isolated than in sera from which strains of low virulence were isolated. The serum interferon assay provides useful presumptive evidence of contamination of rabbit-passaged treponemes with PED virus, but the assay is least useful when PED virus is present subclinically.",,"['Fennestad, K L', 'Bruun, L', 'Haahr, S']",,,,
,PMC,Necrotic Colitis in Two Cats — A Description of the Lesions,,PMC1790165,,,"The lesions in two cases of necrotic colitis in old cats are described. Both had gross lesions of a necrotic, hemorrhagic colitis without gross lesions in the small intestine. Histologically the lesions resembled those of feline panleukopenia virus infection, namely: necrosis and loss of crypt epithelium, dilation of crypts and lining of crypts by flattened epithelium, subsequent collapse of the lamina propria and hemorrhage from subepithelial capillaries. Both grossly and histologically these lesions were restricted to the colon without similar involvement of the small intestine. The histories and clinical signs, the virological and hematological studies suggest that feline panleukopenia virus was not the etiological agent in these cases. No other causal agent was identified.",,"Wilkie, J. S. Nimmo",,,,
,PMC,Role of macrophage activation and interferon in the resistance of alveolar macrophages from infected mice to influenza virus.,,PMC551451,,,"Lung macrophages from uninfected CD1 mice support the replication of influenza viruses (H1N1 and H0N1), but the cells from influenza-infected mice do not. The possible mechanisms of this resistance were investigated. Murine macrophages were ""activated"" in vitro with lipopolysaccharide and lymphokines, and in both cases activation was associated with resistance of cells to infection with influenza virus. Exposure of alveolar macrophages in vitro to 500 U of purified type I interferon per ml enhanced cell spreading and Fc receptor-mediated phagocytosis, suggesting macrophage activation, and protected the cells against infection with influenza virus. Alveolar macrophages were also protected by a soluble factor in the bronchoalveolar washings from influenza-infected mice. This effect was not virus specific and was abolished by anti-interferon serum.",,"['Rodgers, B C', 'Mims, C A']",,,,
,PMC,Faecal adenoviruses from Glasgow babies. Studies on culture and identity.,,PMC2134094,,,"Attempts were made to isolate viruses from babies' stools that contained adenoviruses detected by electron microscopy. One hundred and fifty-nine specimens from 71 children were studied and adenoviruses of established serotypes were isolated from 81 stools. Serial stool samples containing adenovirus particles were obtained from 35 children, and prolonged shedding of recognized serotypes was common. Simultaneous and sequential infections by different serotypes were also observed. Thirty-six children shed adenoviruses that could not be isolated using cell cultures normally used to detect adenoviruses, and nine of these children also shed adenoviruses of established serotypes. Passage in Chang conjunctival cell culture allowed characterization of fastidious adenoviruses from 14 children as members of a previously unrecognized serotype.",,"['Kidd, A. H.', 'Cosgrove, B. P.', 'Brown, R. A.', 'Madeley, C. R.']",,,,
,PMC,Genetic analysis of murine hepatitis virus strain JHM.,,PMC256945,,,"We performed a genetic analysis of 37 temperature-sensitive mutants of murine hepatitis virus strain JHM. Of our mutants, 32 did not induce murine hepatitis virus-specific RNA synthesis in infected cells at the restrictive temperature, 39 degrees C. By complementation testing we have identified at least seven nonoverlapping complementation groups. Six of the genes identified in this way are required for murine hepatitis virus-specific RNA synthesis. The seventh complementation group is made up of five mutants which induced virus-specific RNA synthesis at 39 degrees C.",,"['Leibowitz, J L', 'DeVries, J R', 'Haspel, M V']",,,,
,PMC,Characterization of two RNA polymerase activities induced by mouse hepatitis virus.,,PMC256918,,,"RNA-dependent RNA polymerase activity was found in mouse hepatitis virus strain A59 (MHV-A59)-infected cells. The enzyme was induced in the infected cells and could not be detected in the MHV-A59 virion. Two peaks of RNA polymerase activity, one early and the other late in infection, were detected. These polymerase activities were in temporal sequence with early and late virus-specific RNA synthesis. Both of them were found to be associated with membrane fractions. There were significant differences in the enzymatic properties of the two polymerases. The early polymerase, but not the late polymerase, could be activated by potassium ions in the absence of magnesium ions and also had a lower optimum pH than the late polymerase. It was therefore probable that the enzymes represent two different species of RNA polymerase and perform different roles in virus-specific RNA synthesis. The effects of cycloheximide on MHV-specific RNA synthesis were determined. Continuous protein synthesis was required for both early and late RNA synthesis and might also be required for shutoff of early RNA synthesis.",,"['Brayton, P R', 'Lai, M M', 'Patton, C D', 'Stohlman, S A']",,,,
,PMC,Coronavirus-like Particles in the Feces of a Cat with Diarrhea,,PMC1790106,,,"Coronavirus-like particles were visualized in the feces of a young domestic shorthair female cat with diarrhea. On the surface projections, these particles could be distinguished from the enteric coronavirus-like particles of human, dog, cattle and monkey origin. They appeared morphologically similar to a feline enteric coronavirus recently described by other authors. A precipitin antigen was detected in the cat feces by counterimmunoelectroosmophoresis using a rabbit antibovine coronavirus serum.",,"['Dea, S.', 'Roy, R. S.', 'Elazhary, M. A. S. Y.']",,,,
,PMC,Macrophage antiviral activity: extrinsic versus intrinsic activity.,,PMC351282,,,"Peritoneal exudate cells from strains of mice both resistant and susceptible to challenge with mouse hepatitis virus strain JHM were examined for extrinsic and intrinsic antiviral activity. Thioglycolate-elicited and resident peritoneal cells from uninfected mice were able to suppress viral growth in a permissive cell. The active cell in both populations is an adherent, radiation-resistant, Thy-1.2 antigen- and Ia antigen-negative cell. The suppression of virus replication was not related to nonspecific cellular cytotoxicity directed against the permissive host cell, and no interferon was detected. The expression of extrinsic antiviral activity was not related to the ability of the host to resist mouse hepatitis virus infection by virtue of either age or genetic background. The expression of intrinsic antiviral activity, on the other hand, correlated with the ability of the host to resist virus challenge, indicating a characteristic distinction between these two in vitro mechanisms of macrophage-mediated antiviral activity with regard to host resistance to viral infection. Further, the ability of a macrophage to support viral replication itself was independent of the ability of the macrophage to suppress virus growth in another cell.",,"['Stohlman, S A', 'Woodward, J G', 'Frelinger, J A']",,,,
,PMC,Synthesis of coronavirus mRNAs: kinetics of inactivation of infectious bronchitis virus RNA synthesis by UV light.,,PMC256903,,,Infection of cells with the avian coronavirus infectious bronchitis virus results in the synthesis of five major subgenomic RNAs. These RNAs and the viral genome form a 3' coterminal nested set. We found that the rates of inactivation of synthesis of the RNAs by UV light were different and increased with the length of the transcript. These results show that each RNA is transcribed from a unique promoter and that extensive processing of the primary transcripts probably does not occur.,,"['Stern, D F', 'Sefton, B M']",,,,
,PMC,Bovine coronavirus structural proteins.,,PMC256895,,,"The tissue culture-adapted strain (Mebus) of bovine coronavirus was grown in the presence of isotopically labeled amino acids, glucosamine, or orthophosphate for the purpose of analyzing the virion structural proteins. Five species of polypeptides were identified when purified virions were solubilized in urea and sodium dodecyl sulfate and resolved by polyacrylamide gel electrophoresis. Four species were glycosylated and had apparent molecular weights of 140,000, 120,000, 100,000, and 26,000. The glycoproteins were susceptible to proteolytic cleavage and enzymatic iodination when intact virions were studied and are thus at least partially external to the virion envelope. The 140,000-molecular-weight glycoprotein is apparently a dimer of 65,000-molecular-weight glycopolypeptides held together by disulfide linkages. Species 5 was phosphorylated and had an apparent molecular weight of 52,000. In the intact virion, it was unaffected by protease and was not enzymatically iodinated. It is therefore apparently an internal protein.",,"['King, B', 'Brian, D A']",,,,
,PMC,"Sequence Relationships Between the Genome and the Intracellular RNA Species 1, 3, 6, and 7 of Mouse Hepatitis Virus Strain A59",,PMC256869,,,"We have shown by T(1) oligonucleotide fingerprinting that the genome of mouse hepatitis virus strain A59 and its intracellular RNA 1 have identical fingerprints and that RNA 1 and the subgenomic RNAs 3, 6, and 7 contain common sequences. To localize the homologous region between the RNAs, we compared fingerprints of the 3′ terminus of the genome with those of RNA 7. The genome was partially degraded with alkali, and polyadenylate-containing fragments were purified by oligodeoxythymidylate-cellulose chromatography. The fragments were size fractionated by agarose-urea gel electrophoresis, and two pools, x and z, containing 3′-derived fragments of the genome with apparent molecular weights of 0.1 × 10(6) to 0.14 × 10(6) and 0.6 × 10(6) to 0.8 × 10(6), respectively, were further analyzed by RNase T(1) oligonucleotide fingerprinting. Comparison of the fingerprints of RNAs 6 and 7 with those of pools x and z showed that these subgenomic RNAs extend inwards from the 3′ terminus of the genome. The RNA fragments present in pool z were on average slightly larger than RNA 7 as confirmed by the presence in pool z of T(1) oligonucleotide spots specific for RNA 6 but not present in RNA 7. However, two large oligonucleotide spots derived from RNA 7, which were also present in RNAs 1, 3, and 6 and in the virion RNA, were not found in the T(1) oligonucleotide map of pool z. A possible explanation is that the two spots were derived from a leader sequence. The results of UV transcription mapping experiments (L. Jacobs, W. J. M. Spaan, M. C. Horzinek, and B. A. M. van der Zeijst, J. Virol. 39:401-406, 1981) excluded the possibility that such a leader sequence arises by splicing from a larger precursor molecule, but either a virus-specific RNA primer molecule for the synthesis of mRNAs or an RNA polymerase jumping mechanism could explain the presence of a leader sequence.",,"['Spaan, Willy J. M.', 'Rottier, Peter J. M.', 'Horzinek, Marian C.', 'van der Zeijst, Bernard A. M.']",,,,
,PMC,Types of avian infectious bronchitis strains isolated in Quebec.,,PMC1320270,,,"Between 1976 and 1980, 24 isolates of infectious bronchitis virus were obtained from Quebec flocks. The serological classification of these isolates was demonstrated by cross neutralization tests using antisera to 13 different reference virus strains. Of the 24 isolates, ten were identified as Connecticut, six Holland and one SE-17 types. Seven strains did not react with any of the specific antisera.",,"['Marsolais, G', 'Marois, P']",,,,
,PMC,Semliki Forest Virus Neurovirulence Mutants Have Altered Cytopathogenicity for Central Nervous System Cells,,PMC351223,,,"We have analyzed the pathogenicity and host range properties of four neurovirulence mutants of Semliki Forest virus which, unlike the wild type (WT), allow the survival of weanling mice injected intraperitoneally with 10(2) PFU. The mutant M9 showed a sustained multiplication in the brains of infected mice. It produced paralysis in 35%, and 8% died. Demyelination occurred in 94% of the surviving mice and was associated with the destruction of oligodendrocytes. All of the mutants showed a restricted ability to multiply in BHK, C1300 (neuroblastoma), and G26-24 (oligodendroglioma) cells as compared with the WT, and this was not associated with differential interferon production or action. C1300 cells infected with the mutants survived, whereas WT-infected cells were killed. In G26-24 cells all of the mutants and the WT produced a rapid cytopathic effect which was inhibited by pretreatment with 10 U of mouse interferon. Extensive RNA synthesis was detected for all of the mutants and the WT in BHK and C1300 cells, but it was only detectable in G26-24 cells in small amounts early in the infection. The mutant M4 had a defect in the nucleocapsid assembly, whereas M9 had a defect in total RNA synthesis. M136 was defective in the synthesis of 26S RNA, and M103 showed defective synthesis of viral core protein in C1300 cells. It is concluded that C1300 cells can tolerate viral RNA synthesis by a defective virus without showing a cytopathic effect, but the fully virulent WT virus is cytopathic. G26-24 cells are sensitive to small amounts of viral RNA synthesis. These properties of the WT and mutant viruses correlate with changes produced in the neurons and oligodendrocytes of the central nervous system: the virulence of the WT is due to its ability to destroy both neurons and oligodendrocytes, whereas the demyelination produced by the mutants M9 and M136 is due to the destruction of oligodendrocytes alone.",,"['Atkins, Gregory J.', 'Sheahan, Brian J.']",,,,
,PMC,Structural analysis of virion proteins of the avian coronavirus infectious bronchitis virus.,,PMC256062,,,"We have found six major polypeptides in virions of the avian coronavirus infectious bronchitis virus grown in tissue culture: four glycoproteins, GP84, GP36, GP31, and GP28, and two non-glycosylated proteins, P51 and P23. In addition, we detected three minor species: two glycoproteins, GP90 and GP59, and one non-glycosylated protein, P14. Two-dimensional tryptic peptide mapping showed that GP36, GP31, GP28, and P23 comprise a group of closely related proteins which we have designated the ""P23 family,"" but that the other proteins are distinct. Analysis by partial proteolytic digestion of P23 family, but that the other proteins are distinct. Analysis by partial proteolytic digestion of the P23 family labeled biosynthetically with [35S] methionine, and P23, labeled with [35S] formyl-methionine by in vitro translation of RNA from infected cells, revealed that the proteins of the P23 family differ in their amino-terminal domains. Similar analysis of GP31 and Gp36 labeled with [3H] mannose showed that the partial proteolytic fragments unique to these proteins were glycosylated. This suggests that differences in glycosylation in the amino-terminal domains contributes to the marked polymorphism os the P23 family. The results are discussed with respect to possible models for synthesis of the virion proteins.",,"['Stern, D F', 'Burgess, L', 'Sefton, B M']",,,,
,PMC,RNA-dependent RNA polymerase activity in coronavirus- infected cells.,,PMC256056,,,"An enzymatic activity which incorporates [3H]UMP into acid-precipitable material in the presence of endogenous template was found in the cytoplasm of porcine cells infected with the transmissible gastroenteritis virus of swine. This activity was not found in uninfected control cells, nor was it found in purified virus. The activity was associated with the mitochondrial fraction of infected cells, suggesting that the enzyme is membrane bound. The activity required the presence of all three ribonucleoside triphosphates in addition to [3H]UTP, and it was not inhibited by actinomycin D. The heated product was digested by RNase but not by DNase. Mg2+ was required for enzymatic activity, and its optimal concentration was approximately 5 mM. The size of the in vitro products was compared by electrophoresis with that of in vivo-synthesized virus-specified RNA to confirm the viral specificity of the polymerase activity. Virus-specified RNA from infected cells consisted of 10 species of single-stranded, polyadenylated RNA with molecular weights of 6.8 X 10(6), 6.2 X 10(6), 3.15 X 10(6), 1.40 X 10(6), 1.05 X 10(6), 0.94 X 10(6), 0.66 X 10(6), 0.39 X 10(6), 0.34 X 10(6), and 0.24 X 10(6). In vitro synthesized RNA consisted of a high-molecular-weight species, of apparently higher molecular weight than genomic RNA, and two single-stranded species that electrophoretically comigrated with the species of 1.40 X 10(6) and 0.66 X 10(6) molecular weight made in vivo.",,"['Dennis, D E', 'Brian, D A']",,,,
,PMC,Activation of natural killer cells and induction of interferon after injection of mouse hepatitis virus type 3 in mice.,,PMC351127,,,"High levels of natural killer (NK) cell activity and high titers of interferon were observed in the peritoneal exudate of C57BL/6 mice 20 to 50 h after injection of mouse hepatitis virus type 3 (MHV3) but not during the first 10 h after infection. C57BL/6 mice were susceptible to MHV3 infection and showed high titers of MHV3 in the peritoneal exudate 48 h after infection. A/J mice, in contrast, were resistant to the dose that killed 100% of the C57BL/6 mice (10 macrophage-infecting doses) and showed considerably lower virus titers than those shown by C57BL/6 mice. NK cell activity and interferon titers were significantly lower in the peritoneal exudate of A/J mice than in that of C57BL/6 mice. Serum interferon titers were also lower in A/J mice. Thus, our data show an inverse relationship between resistance and the levels of these two parameters. The data suggest that, in contrast to the situation observed with certain herpesviruses, interferon and NK cells may not be of overwhelming importance in the defense of mice against MHV3.",,"['Schindler, L', 'Engler, H', 'Kirchner, H']",,,,
,PMC,Polypeptides and functions of antigens from human coronaviruses 229E and OC43.,,PMC351070,,,"Coronaviruses possess three major size classes of polypeptides as judged by molecular weight: approximately 180,000, approximately 50,000, and approximately 23,000. Human coronaviruses 229E and OC43 possess not only three similar size classes of polypeptides but also three distinct antigens, none of which cross-react with the heterologous strain. Polypeptides separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were reacted in rocket immunoelectrophoresis with antiserum monospecific to each of the three strain-specific antigens (excised precipitin lines from crossed immunoelectrophoresis profiles were used for immunogens). Monospecific antiserum with neutralizing ability reacted with a polypeptide of 186,000 daltons for 229E and a polypeptide of 190,000 daltons for OC43. The antigen which elicited neutralizing antibody response was located at the surface, associated with the corona of the virion, glycosylated, and bound by concanavalin A. Another less prominent surface antigen was represented by size classes of 23,000 daltons for 229E and 24,000 for OC43. The core antigens of the viruses had molecular weights of 49,000 and 229E and 52,000 and OC43 virus. Thus, the molecular weights and functions of the antigens of human coronaviruses are similar to those of animal coronaviruses. The polypeptides of coronaviruses 229E and OC43 are nearly identical as judged by molecular weight, but the similar polypeptides of the two viruses represent different immunological specificities.",,"['Schmidt, O W', 'Kenny, G E']",,,,
,PMC,"Porcine pararotavirus: detection, differentiation from rotavirus, and pathogenesis in gnotobiotic pigs.",,PMC272083,,,"Some characteristics of a newly recognized porcine enteric virus are described. Tentatively, the virus was referred to as porcine pararotavirus (PaRV) because it resembled rotaviruses in respect to size, morphology, and tropism for villous enterocytes of the small intestine. However, it was antigenically distinct from porcine, human, and bovine rotaviruses and reoviruses 1, 2, and 3, and the electrophoretic migration pattern of PaRV double-stranded RNA was distinct from the electrophoretic migration patterns of the rotaviral and reoviral genomes. By passage in gnotobiotic pigs, PaRV was isolated from two suckling diarrheic pigs originating from two herds. After oral exposure of gnotobiotic pigs, villous enterocytes of the small intestines became infected as judged by immunofluorescence, resulting in villous atrophy and diarrhea. Mortality was high when gnotobiotic pigs less than 5 days old were infected. The C strain of this virus was serially passed 10 times in gnotobiotic pigs, and electron microscopy, immunofluorescence, and serological tests indicated no extraneous agents. The virus was serially passed five times in cell cultures which contained pancreatin in the medium, but replication was negligible or absent, as the number of immunofluorescent cells decreased with each passage. Since rotaviral infections are frequently diagnosed by direct electron microscopy of fecal specimens, the presence of other morphologically similar viruses, such as PaRV, should be considered. The use of immune electron microscopy is suggested as a means of helping recognize this situation.",,"['Bohl, E H', 'Saif, L J', 'Theil, K W', 'Agnes, A G', 'Cross, R F']",,,,
,PMC,Further characterization of mRNA's of mouse hepatitis virus: presence of common 5'-end nucleotides.,,PMC256784,,,"The mouse hepatitis virus strain A59 codes for seven RNA species in the infected cells. These virus-specific RNAs were found to be polysome associated and therefore likely to represent mRNA's. All of them have common 3'-end sequences (Lai et al., J. Virol. 39:823-834, 1981). Their structure was further studied with respect to their 5'-end sequences. It was found that all of these mRNA's contained cap structures at their 5' ends. Furthermore, the cap-containing oligonucleotides which represent the sequences immediately adjacent to the 5' ends were found to be the same for most, if not all, of the seven virus-specific mRNA's. These sequences are also identical to the 5'-end sequences of the virion RNA genome. The 5'-end sequences were tentatively determined to be 5'-cap-N-UAAG. The presence of the common nucleotides in all of the virus-specific RNAs in mouse hepatitis virus strain A59 suggests several possible mechanisms of synthesis for these RNAs. The significance of these findings is discussed.",,"['Lai, M M', 'Patton, C D', 'Stohlman, S A']",,,,
,PMC,Nontoxic staphylococcal pneumonia with empyema in a renal transplant recipient.,,PMC1273557,,,,,"['Spencer, C D', 'Crawford, G E']",,,,
,PMC,Peritoneal macrophage alterations caused by naturally occurring mouse hepatitis virus.,,PMC1915970,,,"During routine harvest of murine resident peritoneal cells for macrophage function assays the authors recently noted that mice showed a 3-4-fold spontaneous increase in number of peritoneal cells within 1 week of being placed in one of their animal rooms. While the mice appeared clinically normal, the collected macrophages had highly convoluted membranes, showed enhanced spontaneous tumor cell killing, and showed increased erythrophagocytosis. Histopathologic findings included mild peritonitis and occasional foci of individual hepatocyte necrosis. The results of routine murine serologic studies and bacterial cultures of the peritoneal cavity were negative. Immunosuppressed mice placed in this room showed severe hepatic necrosis within 4 days, and ultrastructural particles characteristic of corona virus could be demonstrated in the necrotic foci. Mouse hepatitis virus (MHV) was isolated from these livers. Untreated mice showed positive MHV titers, as detected by the enzyme-linked immunoabsorbent assay (ELISA) after 21 days in the room. This episode demonstrates that MHV have profound effects on macrophage parameters while causing few clinical signs or histopathologic alterations. Secondly, the complement fixation assay for MHV as included in routine viral screens appears relatively insensitive for detecting outbreaks of MHV.",,"['Boorman, G. A.', 'Luster, M. I.', 'Dean, J. H.', 'Campbell, M. L.', 'Lauer, L. A.', 'Talley, F. A.', 'Wilson, R. E.', 'Collins, M. J.']",,,,
,PMC,Rotavirus and acute diarrhoeal disease in children in a southern Indian coastal town,,PMC2536013,,,"Rotavirus was found by electron microscopy in the stools of 70.7% of a representative sample (368) of the 3355 children with acute diarrhoea admitted to hospital over a period of 16 months in Calicut on the west coast of India. The prevalence of the virus was high (nearly 100% of cases examined) in the period from November to January and lowest in May just before the onset of the monsoon. Prevalence was high (75.1%) in infants aged from 6 to 23 months, but was considerably lower in those under 6 months of age (34.8%). The management of cases and the planning of control measures for this disease are discussed in the light of knowledge of the high prevalence of rotavirus.",,"['Paniker, C. K. J.', 'Mathew, S.', 'Mathan, M.']",,,,
,PMC,WHO Scientific activities,,PMC2535994,,,,,,,,,
,PMC,Indications concernant la recherche sur les infections aiguës des voies respiratoires: Mémorandum d'une réunion de l'OMS,,PMC2535979,,,,,,,,,
,PMC,Successful experimental challenge of dogs with canine parvovirus-2.,,PMC1320191,,,"Withholding food from dogs for 24 hours prior to, and for 48 hours following oral challenge with a gut mucosal homogenate of canine parvovirus-2, was a successful means of reproducing gastroenteric signs of canine parvovirus-2 infection. Twenty-one of 24 dogs, which had previously received various vaccine preparations of mink enteritis virus or were unvaccinated, and which were starved at challenge, developed soft or liquid feces with large or without large clots of mucus. Altered feces were most frequent on postexposure day 11. Seven dogs passed frank blood in their stools on one or more occasions and seven dogs vomited sporadically. Pyrexia was noted in 71.6% of the dogs on postexposure day 6 and lymphopenia was detected on postexposure day 5 or 6 in 50% of the dogs monitored. In contrast, four dogs not starved at the time of challenge remained free of gastrointestinal signs apart from one dog which passed a soft stool with scant mucus on one day, postexposure day 6. Also four dogs vaccinated with a killed canine parvovirus-2 vaccine preparation and subsequently starved at the time of challenge, remained clinically healthy. Apart from these last mentioned four dogs, all others shed canine parvovirus-2 in their feces following challenge.",,"['Carman, S', 'Povey, C']",,,,
,PMC,Post-translational glycosylation of coronavirus glycoprotein E1: inhibition by monensin.,,PMC553242,,,"The intracellular sites of biosynthesis of the structural proteins of murine hepatitis virus A59 have been analyzed using cell fractionation techniques. The nucleocapsid protein N is synthesized on free polysomes, whereas the envelope glycoproteins E1 and E2 are translated on the rough endoplasmic reticulum (RER). Glycoprotein E2 present in the RER contains N-glycosidically linked oligosaccharides of the mannose-rich type, supporting the concept that glycosylation of this protein is initiated at the co-translational level. In contrast, O-glycosylation of E1 occurs after transfer of the protein to smooth intracellular membranes. Monensin does not interfere with virus budding from the membranes of the endoplasmic reticulum, but it inhibits virus release and fusion of infected cells. The oligosaccharide side chains of E2 obtained under these conditions are resistant to endoglycosidase H and lack fucose suggesting that transport of this glycoprotein is inhibited between the trans Golgi cisternae and the cell surface. Glycoprotein E1 synthesized in the presence of monensin is completely carbohydrate-free. This observation suggests that the intracellular transport of this glycoprotein is also blocked by monensin.",,"['Niemann, H', 'Boschek, B', 'Evans, D', 'Rosing, M', 'Tamura, T', 'Klenk, H D']",,,,
,PMC,The pathogenesis of chronic viral hepatitis in the nude mouse and its influence on liver regeneration after partial hepatectomy.,,PMC2041739,,,"The pathogenesis of chronic viral hepatitis due to infection with mouse hepatitis virus Type 1 has been followed over a period of 30 days in the nu/nu mouse. The initial histopathology is that of a focal hepatic necrosis which evolves into a chronic hepatitis with cirrhosis. The histopathology of the experimentally induced hepatitis with mouse hepatitis Type 1 is indistinguishable from that produced by the disease in nude mouse colonies due to the natural infection in the United Kingdom and also indistinguishable from the histopathology produced by the nude mouse hepatitis virus isolated in Japan. The virus produces a temporary suppression and delay in liver regeneration of nude mice which have been partially hepatectomized and this is compared to the delay in liver regeneration induced by another more virulent strain of mouse hepatitis, Type A59, in the nude mouse.",,"Carthew, P.",,,,
,PMC,Correlation between growth potential of mouse hepatitis viruses in macrophages and their virulence for mice.,,PMC350974,,,"Correlation between the virulence of mouse hepatitis virus (MHV) for mice and the growth potential of the virus in peritoneal adherent cells was observed for highly virulent MHV-2 and avirulent MHV-1, JHM, and MHV-S strains. However, this phenomenon was not observed in strain MHV-3, which multiplied to almost the same degree in peritoneal adherent cells from susceptible and resistant mouse strains.",,"['Taguchi, F', 'Yamaguchi, R', 'Makino, S', 'Fujiwara, K']",,,,
,PMC,Analysis of age-dependent resistance to murine coronavirus JHM infection in mice.,,PMC350921,,,"Resistance to intraperitoneal murine coronavirus JHM infection in mice develops with age. C3H mice were found to be fully susceptible up to the age of 20 days and resistant after 23 days of age. Protection of susceptible animals from death due to infection could be achieved by maternal antibodies or by transfer of spleen cells from immunized, but not from nonimmunized, donor mice. Lack of protection by transfer of unprimed adult spleen cells was not related to immunosuppression by the host. Moreover, resistance of adult mice could not be abrogated by application of lymphocytes from suckling mice, although immune suppression by other means did affect the resistance of adult animals. On the other hand, spleen cells from nonimmunized mice could be primed with inactivated JHM virus in suckling mice and protected these mice from death due to a subsequent virus infection. Thus, the outcome of infection with JHM virus in suckling and adult mice can be influenced by immunological events, but is not exclusively due to the different stages of immune competence.",,"['Pickel, K', 'Müller, M A', 'ter Meulen, V']",,,,
,PMC,Comparison of methods for detection of Mycoplasma pulmonis in experimentally and naturally infected rats.,,PMC274014,,,"Isolation, indirect immunofluorescence, an enzyme-linked immunosorbent assay (ELISA), and histopathological examination of tissues for characteristic lesions were evaluated for their efficiency in detecting Mycoplasma pulmonis infection in rats. Whereas all of the methods were efficient in naturally infected Sprague-Dawley rats, none of the methods consistently detected infection in F344 rats experimentally infected with low doses of the organism. In the experimental infections, however, the success rate of any method was directly related (P less than 0.05) to increasing inoculum dose and time postinoculation. Collectively, the data indicated that isolation of M. pulmonis was the most efficient single detection method and the nasopharyngeal duct was the best single site to culture, although sampling of multiple sites within the respiratory tract increased the rate of isolating the organism. The ELISA was understandably the least sensitive method in the low-dose, experimentally infected rats because of the time required for development of a detectable serum antibody response. Although each of the four methods identified a high percentage of naturally infected rats, the ELISA was the most efficient method in these animals as it was uniformly positive. The use of combinations of methods was found to increase the rate of detection of M. pulmonis infection in both experimentally and naturally infected rats.",,"['Davidson, M K', 'Lindsey, J R', 'Brown, M B', 'Schoeb, T R', 'Cassell, G H']",,,,
,PMC,Viral protein synthesis in mouse hepatitis virus strain A59-infected cells: effect of tunicamycin.,,PMC256635,,,"We identified eight protein species in virions of mouse hepatitis virus strain A59. Based on their sizes, prosthetic groups, and locations in virions, these proteins were designated gp180/E2, gp90/E2, pp54/N, gp26.5/E1, gp25.5/E1, p24/E1, p22/X, and p14.5/Y. The positions of the last two proteins in virions are not known. Host protein synthesis in Sac(-) cells infected with mouse hepatitis virus strain A59 was inhibited, and the following novel proteins appeared: gp150, gp90, p54, gp26.5, gp25.5, p24, p22, and p14.5. Except for gp150, these polypeptides all co-electrophoresed with mouse hepatitis virus strain A59 structural proteins. In addition, all of these proteins could be immunoprecipitated with a convalescent mouse serum or a rabbit antiserum raised against purified disrupted virus. After a 15-min pulse of infected cells with radioactive amino acids at 7h postinfection, gp90 was not detected, whereas gp26.5 and gp25.5 were only labeled to a small extent. During a subsequent chase period gp150 was processed to gp90, whereas the radioactivity in gp26.5 and gp25.5 increased concomitantly with a reduction of label in p24. Tunicamycin, an antibiotic which inhibits the synthesis of glycopeptides bearing N glycosidically linked oligosaccharides, prevented the appearance of gp150 in mouse hepatitis virus strain A59-infected cells. Instead, a 110,000-dalton protein accumulated. In contrast, the syntheses of the smaller viral glycoproteins gp26.5 and gp25.5 were resistant to this drug, indicating that these glycosylations were of the O glycosidical type. Although the production of infectious virus in tunicamycin-treated cells was inhibited by more than 99%, release of noninfectious viral particles continued. An analysis of these particles revealed that they lacked the peplomeric glycoproteins gp90/E2 and gp180/E2. Obviously, although the surface projections were not essential for budding of virus particles from the cells, they were required for infectivity.",,"['Rottier, P J', 'Horzinek, M C', 'van der Zeijst, B A']",,,,
,PMC,Vaccination Guidelines for Dogs and Cats,,PMC1789923,,,,,,,,,
,PMC,Porcine Neonatal Coccidiosis,,PMC1789971,,,"Coccidia were identified in intestinal sections from 82 piglets comprising 37 consignments from 34 farms, and represented a yearly increasing incidence in the three years 1978 to 1980. Piglets were primarily from medium to large farms with intensive, continuous-farrowing, confinement-rearing programs. Piglets, usually five days to 15 days old, had yellow, fluid diarrhea, became unthrifty and sometimes died. In six piglets from two farms, a green, adherent, fibrinonecrotic membrane was seen throughout most of the jejunum and ileum. Significant gross lesions were not observed in the other 76 piglets. Moderate to severe villous atrophy of jejunum and ileum was seen histologically. Various asexual and sexual stages of coccidia were seen within parasitophorous vacuoles of villar epithelial cells. Multifocal erosions with necrosis of villar tips and occasionally more diffuse mucosal necrosis with fibrinocellular exudate were seen. Isospora suis oocysts were identified in feces from several weaners from one farm. Amprolium and decoquinate mixed in the sow ration at 1 kg/tonne for three weeks prior to and postfarrowing was moderately successful in stopping outbreaks of neonatal diarrhea associated with coccidiosis.",,"['Sanford, S. E.', 'Josephson, G. K. A.']",,,,
,PMC,Two antigenic groups of human coronaviruses detected by using enzyme-linked immunosorbent assay.,,PMC350770,,,"Paired sera from volunteers inoculated with one of the five recently isolated strains of human coronavirus (HCV), AD, GI, HO, PA, and RO, none of which has been grown in tissue culture, or with strain OC38 were tested against coronavirus antigens by enzyme-linked immunosorbent assay. When HCV strains OC43, 229E, or the 229E-related tissue culture-adapted strains PR and TO were used as antigens, it was shown that all strains fell into one of two antigenic groups. The HCV OC43 group was comprised of strains OC43, GI, HO, and RO, and the HCV 229E group contained strains AD and PA as well as the tissue culture-adapted strains PR, TO, and KI. Enzyme-linked immunosorbent assay of the paired sera with the coronavirus mouse hepatitis virus strain 3 as antigen confirmed the relationship of this virus to the HCV OC43 group but not to the HCV 229E group.",,"['Macnaughton, M R', 'Madge, M H', 'Reed, S E']",,,,
,PMC,"Rapid, simple method of preparing rotaviral double-stranded ribonucleic acid for analysis by polyacrylamide gel electrophoresis.",,PMC271954,,,"A procedure for extracting rotaviral double-stranded ribonucleic acid (RNA) directly from fecal and intestinal specimens collected from calves and pigs is described. This procedure provides a rapid, simple, reproducible method of obtaining rotaviral double-stranded RNA preparations suitable for electrophoretic analysis in polyacrylamide-agarose composite gels. The rotaviral genome electrophoretic migration pattern produced by double-stranded RNA extracted directly from a specimen by this procedure was qualitatively identical to the electrophoretic migration pattern obtained with double-stranded RNA extracted from purified rotavirus derived from the same specimen. Direct extraction of specimens containing porcine rotavirus-like virus by this procedure gave preparations that had electrophoretic migration patterns similar, but not identical, to the characteristic electrophoretic migration pattern of the rotaviral genome. Sufficient rotaviral double-stranded RNA could be extracted from 6 ml of fecal or intestinal specimen by this procedure to permit 15 or more electrophoretic assays.",,"['Theil, K W', 'McCloskey, C M', 'Saif, L J', 'Redman, D R', 'Bohl, E H', 'Hancock, D D', 'Kohler, E M', 'Moorhead, P D']",,,,
,PMC,Mouse hepatitis virus A59: mRNA structure and genetic localization of the sequence divergence from hepatotropic strain MHV-3.,,PMC171315,,,"The composition and structure of the mouse hepatitis virus (MHV)-specific RNA in actinomycin D-treated, infected L-2 cells were studied. SEven virus-specific RNA species with molecular weights of 0.6 X 10(6), 0.9 X 10(6), 1.2 X 10(6), 1.5 X 10(6), 3.0 X 10(6), 4.0 X 10(6), and 5.4 X 10(6) (equivalent to the viral genome) were detected. T1 oligonucleotide fingerprinting studies suggested that the sequences of each RNA species were totally included within the next large RNa species. The oligonucleotides of each RNA species were mapped on the 60S RNA genome of the virus. Each RNA species contained the oligonucleotides starting from the 3' end of the genome and extending continuously for various lengths in the 3' leads to 5' direction. All of the viral RNA species contained a polyadenylate stretch of 100 to 130 nucleotides and probably identical sequences immediately next to the polyadenylate. These data suggested that the virus-specific RNAs are mRNA's and have a stairlike structure similar to that of infectious bronchitis virus, an avian coronavirus. A proposal is presented, based on the mRNA structure, for the designation of the genes on the MHV genome. Using this proposal, the sequence differences between A59, a weakly pathogenic strain, and MHV-3, a strongly hepatotropic strain, were localized primarily in mRNA's 1 and 3, corresponding t genes A and C.",,"['Lai, M M', 'Brayton, P R', 'Armen, R C', 'Patton, C D', 'Pugh, C', 'Stohlman, S A']",,,,
,PMC,Foodborne gastroenteritis of unknown aetiology: a virus infection?,,PMC1507922,,,,,"Carson, J",,,,
,PMC,Salmonella choleraesuis septicemia in calf.,,PMC1789968,,,,,"['Cécyre, A', 'Paul, M', 'Couture, Y', 'Lamothe, P']",,,,
,PMC,Inhibition of the Mitotic Response in Regenerating Mouse Liver During Viral Hepatitis,,PMC350750,,,"Viral hepatitis caused by infection with murine hepatitis virus strain A59 has been shown to affect the mitotic response after partial hepatectomy in mice. Normal mice showed a delayed response, whereas nude mice did not show any response, even 5 days after partial hepatectomy.",,"Carthew, P.",,,,
,PMC,"Diarrhea in lambs: experimental infections with enterotoxigenic Escherichia coli, rotavirus, and Cryptosporidium sp.",,PMC350712,,,"Thirteen gnotobiotic lambs, aged from a few hours to 8 days, were inoculated orally with single infections of enterotoxigenic Escherichia coli (ETEC) (four animals), lamb rotavirus (five animals), and Cryptosporidium (four animals). Six gnotobiotic and two specific-pathogen-free lambs were co-inoculated with either rotavirus and ETEC (four animals), rotavirus and Cryptosporidium (two animals), or ETEC and Cryptosporidium (two animals). Lambs 4 days of age and older became only subclinically infected with either rotavirus, ETEC (08:K87:K99 ST+), or both enteropathogens given simultaneously. Six-day-old lambs inoculated with Cryptosporidium became extremely depressed, anorectic, and had intermittent diarrhea. There was no difference in the clinical manifestations, level of disaccharidase activity in the small intestine, or extent of histological damage between lambs inoculated with Cryptosporidium alone or together with either of the other two agents. The results indicate that under the conditions of these experiments, lambs become clinically resistant to infection with ETEC, rotavirus, or both agents together, by 4 days after birth, whereas lambs 2 days old or younger were clinically susceptible to infection by these agents. In contrast, they remained clinically susceptible to infection with Cryptosporidium up to at least 6 days of age. Cryptosporidium infections were not aggravated by coinfection with either ETEC or rotavirus.",,"['Tzipori, S', 'Sherwood, D', 'Angus, K W', 'Campbell, I', 'Gordon, M']",,,,
,PMC,"Acute diarrhea and rotavirus infection in newborn babies and children in Yogyakarta, Indonesia, from June 1978 to June 1979.",,PMC271920,,,"A longitudinal study of acute diarrhea in children in Yogyakarta, Indonesia (June 1978 to June 1979), showed little variation throughout most months of the year in numbers of children admitted to hospital and in numbers infected with rotaviruses. Both decreased during November and December coincidentally with seasonal change from dry to wet conditions. Rotavirus particles were identified by electron microscopy in fecal specimens from 126 of 334 (38%) infants and children with acute diarrhea. Nosocomial rotavirus infections occurred in 11% of control children admitted to hospital for other reasons. Socioeconomic level and preexisting nutritional status did not influence the incidence of rotavirus excretion. Rotavirus infections were most common in children aged 6 to 24 months. There was a low incidence of infection in infants less than 6 months old. Rotavirus infection was seldom observed in newborn babies delivered in an urban hospital nursery, in a rural health center, or at home. One of 72 newborn babies with diarrhea excreted rotavirus. One of 53 healthy newborn babies excreted rotavirus. It is concluded that, in Indonesia, rotavirus infection is a major cause of childhood diarrhea throughout the year, but is an uncommon cause of diarrhea in newborn babies.",,"['Soenarto, Y', 'Sebodo, T', 'Ridho, R', 'Alrasjid, H', 'Rohde, J E', 'Bugg, H C', 'Barnes, G L', 'Bishop, R F']",,,,
,PMC,Synthesis of subgenomic mRNA's of mouse hepatitis virus is initiated independently: evidence from UV transcription mapping.,,PMC171348,,,"The target sizes of the templates for the synthesis of the genome-sized RNA and the six subgenomic RNAs found in cells infected with mouse hepatitis virus strain A59 were determined by UV transcription mapping. Infected Sac(-) cells were irradiated at 6 h postinfection, the time when virus-specific RNA synthesis starts to increase exponentially. The effect of increasing UV doses on the synthesis of the individual RNAs was determined by quantitation of these RNAs after separation by agarose gel electrophoresis. The UV target sizes calculated for the templates were almost identical to the physical sizes of the RNAs. The results of these experiments seem to exclude the possibility that the subgenomic RNAs are processed or spliced from a common precursor. The data are consistent with independent initiation of transcription on a genome-sized, negative-stranded template or on smaller templates.",,"['Jacobs, L', 'Spaan, W J', 'Horzinek, M C', 'van der Zeijst, B A']",,,,
,PMC,Variation in human rotavirus electropherotypes occurring between rotavirus gastroenteritis epidemics in central Australia.,,PMC350646,,,"The changes in human rotavirus electropherotypes, occurring during a period including two rotavirus gastroenteritis epidemics in 1976 and 1979 in relatively remote Central Australia, were determined by polyacrylamide gel electrophoretic analysis of the rotavirus genome ribonucleic acid. A number of different electropherotypes were present during each of the epidemics, although a single type was predominant in each one. The predominant electropherotype of the first epidemic persisted in the area for approximately 2 years afterwards. Apart from this electropherotype, only three others were recognized in the 3 years between the two epidemics. One of these, first seen 1 year before the second epidemic, bore a very close similarity to the predominant type of the second epidemic. Altogether, 12 different electropherotypes were recognized during the period of the survey. No type common to both areas was found when rotavirus electropherotypes recognized in Central Australia were compared with those detected in a 1973-to-1979 survey in Melbourne, Australia.",,"['Schnagl, R D', 'Rodger, S M', 'Holmes, I H']",,,,
,PMC,Diarrhea due to Cryptosporidium infection in artificially reared lambs.,,PMC271908,,,"Severe diarrhea which lasted 7 to 12 days occurred in 40 of 48 artificially reared lambs within 5 to 12 days of birth, and 16 of them died. Of 16 diarrheic fecal samples examined, 10 contained Cryptosporidium oocysts and 1 contained rotavirus, but no other known enteropathogen was detected. Upon histological examination, cryptosporidia were found in the ilea of three affected lambs, and in one of them, villous atrophy and fusion, with epithelial cross-bridging between villi, were present in distal small intestine. Diarrhea was induced in two specific pathogen-free lambs by oral inoculation with fecal homogenate containing Cryptosporidium oocysts. Both the small and large intestines became infected with the organism, and associated lesions included stunting, fusion, and deformities of villi in the distal small intestine, with replacement of columnar enterocytes by immature cuboidal cells. Subclinical infections were induced in newborn specific pathogen-free mice and rats. Judged by these data, the lamb-derived Cryptosporidium sp. is similar to those recovered from calves, deer, and humans.",,"['Tzipori, S', 'Angus, K W', 'Campbell, I', 'Clerihew, L W']",,,,
,PMC,Oligonucleotide Fingerprinting of Ribonucleic Acids of Infectious Bronchitis Virus Strains,,PMC351583,,,"A total of 11 distinct oligonucleotide fingerprints were obtained in studies of the ribonucleic acids of 13 isolates of infectious bronchitis virus. Different serotypes had distinct fingerprints, but so did varieties within a serotype, allowing a greater degree of strain differentiation than was previously possible. Some conclusions can be drawn from the fingerprints concerning theories of origin and spread of infectious bronchitis virus.",,"['Clewley, J. P.', 'Morser, J.', 'Avery, R. J.', 'Lomniczi, B.']",,,,
,PMC,Protection of mice against mouse hepatitis virus by Corynebacterium parvum.,,PMC351569,,,"C57BL/6 mice that are highly susceptible to infection with mouse hepatitis virus type 3 were protected against intraperitoneal viral infection by simultaneous intraperitoneal injection of Corynebacterium parvum. No protection was observed when C. parvum was given intravenously or when it was injected intraperitoneally 3 days before viral infection. Protective effects were, however, consistently found when C. parvum was given 2 h before or 2 h after viral infection. Activity was seen only against 10 50% lethal doses and not against 100 50% lethal doses. C. parvum also caused a significant decrease of virus type 3. These data suggest a direct effect of C. parvum on virus-susceptible cells. Injection of C. parvum in mice caused activation of natural killer (NK) cells and of interferon production. However, these two effects were equally demonstrable at high and low doses of C. parvum, whereas protection against mouse hepatitis virus type 3 was not demonstrable at low doses of C. parvum. Thus, antiviral protection may be dissociated from activation of NK cells and induction of interferon.",,"['Schindler, L', 'Streissle, G', 'Kirchner, H']",,,,
,PMC,Immunogenicity and antigenicity of human coronaviruses 229E and OC43.,,PMC351550,,,"The immunogenicity and antigenicity of human coronaviruses 229E and OC43 were studied by quantitative immunoelectrophoresis. Three distinct antigens were recognized in both coronavirus strains when T-100-solubilized whole virus was tested by two-dimensional immunoelectrophoresis against homologous rabbit antiserum. No antigens cross-reacted between strains, but the electrophoretic patterns against homologous antiserum were highly similar in that both strains had one electrophoretically fast antigen, one of intermediate mobility, and one of slow mobility. Immunization of rabbits with 10(9) plaque-forming units of virus was required for production of antiserum which recognized the three antigens; lesser amounts gave rise to antisera which recognized only one or two components. Precipitin lines excised from two-dimensional immunoelectropherograms were used successfully as immunogens to prepare monospecific antiserum to each of the antigens of OC43 and 229E. Monospecific antiserum to the slow component of 229E neutralized 229E only, and monospecific antiserum to the slow component of OC43 both neutralized and inhibited hemagglutination of OC43 virus. Human convalescent sera which possessed both complement-fixing and neutralizing antibody also recognized the slow-moving component.",,"['Schmidt, O W', 'Kenny, G E']",,,,
,PMC,Clinical manifestations of diarrhea in calves infected with rotavirus and enterotoxigenic Escherichia coli.,,PMC273940,,,"The susceptibility of gnotobiotic, colostrum-derived, or suckling calves to four bovine rotavirus isolates was found to be age dependent. Calves older than 7 days remained clinically normal, although they excreted virus in their feces and subsequently developed antibody against the virus, Enterotoxigenic Escherichia coli, fed to gnotobiotic, colostrum-deprived, or suckling calves ranging in age from a few hours to 26 days old, only caused diarrhea in animals younger than 24 h old. In contrast, diarrhea was consistently induced in 1- and 2-week-old calves infected with both enterotoxigenic E. coli and rotavirus. In general, diarrhea appeared after a rotavirus incubation period of approximately 3 days and was independent of the order in which the two microbial agents were given, the age of the calf, or the level of circulating rotavirus antibodies. The disease episode coincided with the excretion of rotavirus, rather than enterotoxigenic E. coli, in the feces. Infection with enterotoxigenic E. coli became established within 24 h of inoculation, and in older calves enterotoxigenic E. coli was often excreted in very small numbers and for a longer period than rotavirus.",,"['Tzipori, S R', 'Makin, T J', 'Smith, M L', 'Krautil, F L']",,,,
,PMC,Human rotavirus antigen detection by enzyme-immunoassay with antisera against Nebraska calf diarrhoea virus.,,PMC493649,,,"A four-layer solid phase enzyme-immunoassay (EIA) with antisera against Nebraska calf diarrhoea virus (NCDV) as immunoreagents was developed to detect human rotavirus antigens from stool specimens of patients with acute rotavirus gastroenteritis. Polystyrene beads were used as the solid phase, guinea-pig and rabbit anti-NCDV immunoglobulin as the catching and secondary antibody, and peroxidase-conjugated swine anti-rabbit immunoglobulin as the indicator antibody. A comparison of the developed NCDV-EIA with an identical EIA, using antisera against human rotavirus (HRV-EIA) instead of NCDV antisera, was made with 216 stool specimens positive or negative for rotavirus. A complete agreement was obtained between the two methods provided that appropriate confirmatory tests were included. The developed NCDV-EIA was as sensitive and specific for rotavirus as the HRV-EIA, and it allowed the detection of both established rotavirus types 1 and 2 from stools with equal sensitivity. The difficulties in cultivating human rotavirus in vitro for immunisation and the relative ease of growing NCDV in widely-used continuous cell lines make NCDV a good alternative in the preparation of the highly specific and sensitive rotavirus antisera required in immunoassays, and facilitate the setting-up methods for the routine diagnosis of rotavirus gastroenteritis by EIA or RIA in diagnostic virus laboratories.",,"Sarkkinen, H K",,,,
,PMC,Alleged Mycotoxicosis in Swine: Review of a Court Case,,PMC1790048,,,"Vomition and diarrhea in feeder pigs, and signs of hyperestrogenism in sows and pregnant gilts in a large swine operation were thought to be caused by mycotoxins. Various toxicoanalytical tests performed were negative and the cause of the disease was never clearly established. On the basis of the Sale of Goods legislation, a court ruled that the company supplying the feed was responsible for the losses that occurred. The veterinary and legal aspects of the case are reviewed, and it is concluded that there is a need for reliable and readily available laboratory diagnosis of toxins in feedstuff. The importance of gathering whatever evidence is available and of conducting whatever tests are capable of being conducted, is stressed.",,"['Schiefer, H. B.', ""O'Ferrall, B. K.""]",,,,
,PMC,Antibody to human adenovirus early antigens during acute adenovirus infections.,,PMC351513,,,"The antibody (Ab) response to human adenovirus (AV) early antigens (EA) in acute AV infections was studied by the immunoperoxidase antibody technique for determining virus-specific immunoglobulin G (IPA-IgG). AV-EA-Ab appeared about 5 days after the onset of clinical symptoms, reached a peak 15 to 30 days later, and declined in titer after a few months. The staining pattern in the IPA-IgG reaction was usually nuclear; however, in most primary infections sera obtained 2 to 3 weeks after the onset of infection also showed cytoplasmic staining. According to the recent deoxyribonucleic acid homology classification of human AV in five groups (A, B, C, D, and E), the EA-Ab response in primary human infections was found to be group specific for groups A to D, with consistent cross-reactions with group E. In AV type 4 (group E) infections, EA-Ab appeared to be directed against all groups, although at different titers. Comparable results were obtained using AV type-specific animal antisera. Thus, it was concluded that group E shares EA with all the other groups. Furthermore, in each individual with remote AV infections, the current infection elicited an anamnestic EA-Ab response to all AV groups responsible for previous infections. In diagnostic virology these findings can be applied to the rapid diagnosis of a current for recent) AV infection on a single serum sample and to the rapid group identification of clinical isolates by using type-specific animal antisera containing EA-Ab (one for each group) or sera from patients with primary AV infections.",,"['Gerna, G', 'Cattaneo, E', 'Revello, M G', 'Battaglia, M', 'Achilli, G']",,,,
,PMC,Comparative analysis of RNA genomes of mouse hepatitis viruses.,,PMC171196,,,"The RNA genomes of various murine hepatitis virus (MHV) strains were studied by T1-oligonucleotide fingerprinting analysis with regard to their structure and sequence relationship. It was found that the MHV particles contained only positive-stranded 60S RNA which had a ""cap"" structure at its 5' end. No negative-stranded RNA was found. It was also shown that most of the MHV strains had diverged quite extensively in their genetic sequences. However, MHV-3, a hepatotropic strain, and A59, a nonpathogenic strain, were found to have very similar oligonucleotide fingerprinting patterns. Yet, each of them contained two to four specific oligonucleotides. The MHV-3-specific oligonucleotides were conserved in almost all of the hepatotropic MHV strains studied. In contrast, two of the A59-specific oligonucleotides were absent from the genomes of all hepatotropic strains. These findings suggest that these unique oligonucleotides might be localized at the genetic region(s) associated with viral pathogenicity or other biological properties of the virus. Comparison of viral structural proteins also suggests that MHV-3 and A59 are more closely related than other MHV strains. The significance of these findings is discussed.",,"['Lai, M M', 'Stohlman, S A']",,,,
,PMC,Inner structures of some coronaviruses.,,PMC1320148,,,"When treated with formaldehyde, Tween 80, sodium oleate and Nonidet P-40, avian infectious bronchitis virus, porcine transmissible gastroenteritis virus, neonatal calf diarrhea coronavirus, porcine hemagglutinating encephalomyelitis virus as well as the human coronavirus show similar inner structures by negative staining. The first one is an inner membranous bag. This structure could be evaginated following treatments used and does not show the characteristic projections of coronaviruses. Subsequently, the inner fold could be separated from the outer membrane at the point of junction between these two membranes. Each virus does not react in the same way to the action of the different products. The transmissible gastroenteritis virus appears more sensitive to treatments than other viruses. On the other hand, the hemagglutinating encephalomyelitis virus is the most resistant. The variable sensitivities of these viruses are not related to the type of host-cells. Also, a second internal structure, which is more dense than the viral particle, encircles partially the aperture of the internal tongue-shaped structure and seems to emerge from the viral particle through the aperture of the inner bag.",,"['Lamontagne, L', 'Marois, P', 'Marsolais, G', 'Di Franco, E', 'Assaf, R']",,,,
,PMC,Diagnostic des avortements infectieux chez les bovins laitiers.,,PMC1320145,,,"During a two year period, March 1977 to April 1979, a total of 92 bovine abortions were studied. The cause of abortion was determined in 34.8% of the cases examined. Opportunistic bacteria, the most commonly diagnosed cause of abortion, accounted for 31.2% of the cases. Leptospirosis was associated with 28.1% of the abortions, infectious bovine rhinotracheitis and fungi in respectively 15.7%, bovine viral diarrhea in 6.2%. A congenital abnormality accounted for one case (3.1%). In 23 cases (25%), there was no definitive diagnosis, in spite of evidence of experience with pathogen or suggestive findings of pathology, but insufficient evidence to warrant diagnosis. No findings were recorded in 35.8% of the (possibly noninfectious) cases and in only four cases (4.4%), specimens were unsatisfactory for examination.",,"['Higgins, R', 'Hoquet, F', 'Marsolais, G', 'Montpetit, C', 'Elazhary, Y', 'Morin, M', 'Bois, J M', 'Ethier, R']",,,,
,PMC,High interferon titer in newborn pig intestine during experimentally induced viral enteritis.,,PMC350581,,,We looked for the presence of interferon in the digestive tract of newborn piglets infected with a virulent strain of transmissible gastroenteritis virus (Coronaviridae). High levels of type 1 interferon activity were found early in the disease in jejunal and ileal parts of the intestine as well as in the serum. Enterocytes appeared to be involved in the interferon synthesis. These findings raise the question of the role of interferon in the pathogenesis of viral enteritis.,,"['La Bonnardiere, C', 'Laude, H']",,,,
,PMC,"Coronavirus isolates SK and SD from multiple sclerosis patients are serologically related to murine coronaviruses A59 and JHM and human coronavirus OC43, but not to human coronavirus 229E.",,PMC171144,,,"Two coronaviruses (SK and SD), isolated from fresh autopsy brain tissue from two multiple sclerosis patients, were compared with known human and murine coronaviruses. In plaque neutralization assays, antisera prepared against multiple sclerosis isolates SK and SD demonstrated significant cross-reactivity to each other and to murine coronavirus A59, weak cross-reactivity to murine coronavirus JHM, but no cross-reactivity to the human coronavirus 229E. Antiserum to SK or SD failed to inhibit hemagglutination of chicken erythrocytes by the human coronavirus OC43. However, OC43 antiserum neutralized both SD and SK. Specific coronavirus polypeptides were identified and compared by immunoprecipitation and polyacrylamide gel electrophoresis. Infected and mock-infected 17Cl-1 cells were pretreated with actinomycin D and labeled with [35S]methionine. Polypeptides in Nonidet P-40 cytoplasmic extracts were immunoprecipitated with homologous and heterologous antisera. Identical polypeptides were precipitated from A59-, SD-, or SK-infected cell extracts by SD, SK, OC43, or A59 antisera. The polypeptides of human virus 229E were antigenically distinct, with the exception of weak recognition of a polypeptide of 50,000 molecular weight. We conclude that the two multiple sclerosis virus isolates SK and SD are closely related serologically to the murine coronavirus A59 and the human coronavirus OC43.",,"['Gerdes, J C', 'Klein, I', 'DeVald, B L', 'Burks, J S']",,,,
,PMC,Translation of three mouse hepatitis virus strain A59 subgenomic RNAs in Xenopus laevis oocytes.,,PMC171121,,,"We have purified the seven virus-specific RNAs which were previously shown to be induced in Sac(-) cells upon infection with mouse hepatitis virus strain A59 (W. J. M. Spaan, P. J. M. Rottier, M. C. Horzinek, and B. A. M. van der Zeijst, Virology 108:424-434, 1981). The individual RNAs, prepared by agarose gel electrophoresis of the polyadenylated RNA fraction from infected cells, were obtained pure, except for the preparations of RNAs 4, 5, and 6, which contained some contamination of RNA 7. The RNAs were microinjected into Xenopus laevis oocytes, and after incubation of these cells in the presence of [35S]methionine, the proteins synthesized were analyzed by polyacrylamide gel electrophoresis. Whereas no translation products of RNAs 1, 2, 4, and 5 were detected, the synthesis of virus-specific polypeptides coded by RNAs 3, 6, and 7 was observed. RNA 7 (0.6 X 10(6) daltons) directed the synthesis of a 54,000-molecular-weight polypeptide which comigrated with viral nucleocapsid protein and which was immunoprecipitated by antiserum from mice that had been infected with the virus. RNA 6 (0.9 X 10(6) daltons) directed the synthesis of three polypeptides with molecular weights of 24,000, 25,500, and 26,500, which migrated with the same electrophoretic mobilities as three low-molecular-weight virion polypeptides. After injection of RNA 3 (3.0 X 10(6) daltons), a polypeptide with a molecular weight of about 150,000 was immunoprecipitated. This polypeptide had no counterpart in the virion, but comigrated with a virus-specific glycoprotein present in infected cells which is immunoprecipitated by a rabbit antiserum against the mouse hepatitis virus strain A59 structural proteins. This antiserum could also immunoprecipitate the translation products of RNAs 3, 6, and 7. These results indicate that RNAs 3, 6, and 7 encode viral structural proteins. The significance of the data with respect to the strategy of coronavirus replication is discussed.",,"['Rottier, P J', 'Spaan, W J', 'Horzinek, M C', 'van der Zeijst, B A']",,,,
,PMC,La diarrhée néonatale due au coronavirus de veau. Une revue de la littérature,,PMC1789880,,,"CALF CORONAVIRUS NEONATAL DIARRHEA. A LITERATURE REVIEW: The importance of the calf coronavirus in the etiology of neonatal diarrhea of calves has been reported many times from various countries. A literature review concerning this virus is presented in this paper. A detailed description of the pathogenesis, clinical signs and lesions of the disease, as well as the morphological, physicochemical, biological and antigenic characteristics of the virus are presented. The immunity of the calf against this virus and the principal diagnosis technics are also discussed.",,"['Dea, S.', 'Roy, R. S.', 'Elazhary, M. A. S. Y.']",,,,
,PMC,Enhancement of plaque formation and cell fusion of an enteropathogenic coronavirus by trypsin treatment.,,PMC351445,,,"Plaque formation, replication, and related cytopathic functions of the enteropathogenic bovine coronavirus strain L9 in bovine fetal thyroid (BFTy) and bovine fetal brain (BFB) cells were investigated in the presence and absence of trypsin. Plaque formation was enhanced in both cell types. Plaques reached a size with an average diameter of 5 mm within 4 days with trypsin in the overlay, whereas their diameter remained less than 1 mm at this time after plating without trypsin in the overlay. Fusion of both cell types was observed 12 to 18 h after infection when trypsin was present in the medium. Fusion was not observed in infected BFB cell cultures and was rarely observed 48 h after infection of BFTy cells maintained with the trypsin-free medium. The largest polycaryons formed had 15 to 22 nuclei. They then lysed and detached. Cell fusion depended on de novo synthesis of hemagglutinin and infectivity. Fusion from without was not observed. Virus produced under trypsin-enhancing conditions accompanied by cell fusion did not lyse mouse erythrocytes that reacted with L9 coronavirus hemagglutinin. Trypsin-treated, infected BFTy cultures produced coronaviral particles that excluded stain from the envelope confinement. These virions had uniformly shorter surface projections than did the viral forms generated by trypsin-free cell cultures.",,"['Storz, J', 'Rott, R', 'Kaluza, G']",,,,
,PMC,Antibody to virus components in volunteers experimentally infected with human coronavirus 229E group viruses.,,PMC351395,,,"Antibody rises to various virus subcomponents were measured by enzyme-linked immunosorbent assay in the paired sera of volunteers experimentally infected with human coronavirus 229E group viruses. Most of the antibody made during infection was directed against the virus surface projections, with only small amounts of antibody made against membrane or ribonucleoprotein components.",,"['Macnaughton, M R', 'Hasony, H J', 'Madge, M H', 'Reed, S E']",,,,
,PMC,Lactose tolerance in lambs with rotavirus diarrhoea.,,PMC1419231,,,"It has been suggested that lactose malabsorption is an important factor in producing the diarrhoea of acute rotavirus infection. Accordingly, the lactose tolerance of gnotobiotic newborn lambs, infected with lamb rotavirus, has been investigated by clinical studies and tissue enzyme assays. Although lactase activity is low in affected areas of the small intestine, rotavirus infected lambs are not lactose intolerant as assessed by the measurement of reducing substances in the faeces, or by the clinical effects and blood glucose levels after a 5.8 mmol (2 g)/kg lactose load on the second day post-infection. Lactose intolerance could be demonstrated by using extremely high (29.2 mmol (10 g)/kg) doses of lactose, three or four times the normal dietary lactose intake. These experiments suggest that lactose-containing feeds (such as maternal milk) are not necessarily contraindicated in patients or animals with rotavirus diarrhoea.",,"['Ferguson, A', 'Paul, G', 'Snodgrass, D R']",,,,
,PMC,"Detection of antirotavirus immunoglobulins A, G, and M in swine colostrum, milk, and feces by enzyme-linked immunosorbent assay.",,PMC351387,,,"An enzyme-linked immunosorbent assay was developed to allow direct detection of class-specific antirotavirus antibodies. In colostrum and in milk, antirotavirus antibodies were found in the three immunoglobulin classes. Antirotavirus immunoglobulins G and M were predominant in colostrum, whereas antirotavirus immunoglobulin A was predominant in milk and feces.",,"['Corthier, G', 'Franz, J']",,,,
,PMC,"A comparison of lyphogel, ammonium sulphate, and ultracentrifugation in the concentration of stool viruses for electron microscopy.",,PMC1146463,,,,,"['Rodgers, F G', 'Chapman, S', 'Whitby, H']",,,,
,PMC,Maladies à virus des voies respiratoires: vaccins et agents antiviraux,,PMC2396110,,,,,"Lennette, Edwin H.",,,,
,PMC,Viral respiratory diseases: vaccines and antivirals,,PMC2396058,,,"Acute respiratory diseases, most of which are generally attributed to viruses, account for about 6% of all deaths and for about 60% of the deaths associated with all respiratory disease. The huge cost attributable to viral respiratory infections as a result of absenteeism and the disruption of business and the burden of medical care makes control of these diseases an important objective. The viruses that infect the respiratory tract fall taxonomically into five viral families. Although immunoprophylaxis would appear to be the logical approach, the development of suitable vaccines has been confronted with numerous obstacles, including antigenic drift and shift in the influenzaviruses, the large number of antigenically distinct immunotypes among rhinoviruses, the occurrence after immunization of rare cases of a severe form of the disease following subsequent natural infection with respiratory syncytial virus, and the risk of oncogenicity of adenoviruses for man. Considerable expenditure on the development of new antiviral drugs has so far resulted in only three compounds that are at present officially approved and licensed for use in the USA. Efforts to improve the tools available for control should continue and imaginative and inventive approaches are called for. However, creativity and ingenuity must operate within the constraints imposed by economic, political, ethical, and legal considerations.",,"Lennette, Edwin H.",,,,
,PMC,WHO Scientific activities,,PMC2396051,,,,,,,,,
,PMC,WHO Scientific activities,,PMC2396040,,,,,,,,,
,PMC,Enzyme-Linked Immunosorbent Assay for Detection of Antibody in Volunteers Experimentally Infected with Human Coronavirus 229E Group Viruses,,PMC273764,,,,,,,,,
,PMC,Evidence that the genome of hepatitis A virus consists of single-stranded RNA.,,PMC171023,,,"Nucleic acid was extracted from purified hepatitis A virus, radiolabeled with 125I, and shown to consist of single-stranded RNA which sediments at 35S and contains sequences of polyadenylic acid. These findings are consistent with hepatitis A virus being a member of the genus Enterovirus within the family Picornaviridae.",,"['Coulepis, A G', 'Tannock, G A', 'Locarnini, S A', 'Gust, I D']",,,,
,PMC,Restricted replication of human hepatitis A virus in cell culture: intracellular biochemical studies.,,PMC170998,,,"When hepatitis A virus was inoculated into Vero cells, virus-specified protein and RNA synthesis was detected. Production of viral protein was detected by electrophoretic analysis in polyacrylamide gels by using a double-label coelectrophoresis and subtraction method which eliminated the contribution of host protein components from the profiles of virus-infected cytoplasm. Eleven virus-specified proteins were detected in the net electrophoretic profiles of hepatitis A virus-infected cells. The molecular weights of these proteins were very similar to those detected in cells infected with poliovirus type 1. Virus-specified protein synthesis could be detected at 3 to 6 h and continued for at least 48 h postinfection, but no significant effect on host-cell macromolecular synthesis was observed. Limited viral RNA replication occurred between 2 and 6 h postinfection. The genomic RNA of hepatitis A virus was extracted and shown to be capable of infecting cells and inducing the same set of proteins as intact virus, indicating that the RNA genome is positive stranded. Progeny virus was never detected in the supernatant fluids of infected cell cultures, and the cells showed no observable cytopathology, even though hepatitis A virus-specific proteins and antigens were being produced. The nature of the defect in the replicative cycle of hepatitis A virus in this system remains unknown.",,"['Locarnini, S A', 'Coulepis, A G', 'Westaway, E G', 'Gust, I D']",,,,
,PMC,Criteria for development of animal models of diseases of the gastrointestinal system.,,PMC1903637,,,,,"Cheville, N. F.",,,,
,PMC,Clinical genetics & counseling,,PMC1686161,,,,,,,,,
,PMC,Coronavirus multiplication strategy. II. Mapping the avian infectious bronchitis virus intracellular RNA species to the genome.,,PMC353660,,,"Avian infectious bronchitis virus, a coronavirus, directed the synthesis of six major single-stranded polyadenylated RNA species in infected chicken embryo kidney cells. These RNAs include the intracellular form of the genome (RNA F) and five smaller RNA species (RNAs A, B, C, D, and E). Species A, B, C, and D are subgenomic RNAs and together with the genome form a nested sequence set, with the sequences of each RNA contained within every larger RNA species (D. F. Stern and S. I. T. Kennedy, J. Virol 34:665-674, 1980). In the present paper we show by RNase T1 oligonucleotide fingerprinting that RNA E is also a member of the nested set. Partial alkaline fragmentation of the genome followed by sucrose fractionation, oligodeoxythymidylate-cellulose chromatography, and RNase T1 fingerprinting gave a partial 3'-to-5' oligonucleotide spot order. A comparison of the oligonucleotides of each of the five subgenomic RNAs with this spot order established that all of the RNAs are comprised of nucleotide sequences inward from the 3' end of the genome. This result is discussed in relation to the multiplication strategy both of coronaviruses and of other RNA-containing viruses.",,"['Stern, D F', 'Kennedy, S I']",,,,
,PMC,Scanning electron microscopy of intestine of gnotobiotic piglets infected with porcine rotavirus.,,PMC1320097,,,"The development of intestinal lesions caused by the porcine rotavirus were studied in six day old gnotobiotic piglets by scanning electron microscopy. The onset of diarrhea followed an incubation period of 17 to 31 hr. The first detectable lesion was observed in the ileum at 12 hr postinfection, a few hours before the onset of diarrhea. At this time enterocytes appeared swollen and began to separate from each other. Seventeen hours after the onset of diarrhea, lesions were quite severe jejunum and ileum. Enterocytes were detaching from the lamina propria leaving denuded areas. Microvilli were sparse on the cell surfaces and there was marked villous atrophy. Regeneration of ileal mucosa was evident at 4.8 days after the onset of diarrhea. Nine days after recovery from diarrhea the intestinal villi had returned to near its normal structure but there remained some evidence of mucosal damage.",,"['Torres-Medina, A', 'Underdahl, N R']",,,,
,PMC,Enzyme-linked immunosorbent assay for detection of antibody in volunteers experimentally infected with human coronavirus strain 229 E.,,PMC273622,,,"An enzyme-linked immunosorbent assay was developed for detecting antibody rises to human coronavirus strain 229E and related strains in paired sera from infected volunteers. There was a close correlation between development of colds infected volunteers. There was a close correlation between development of colds and significant antibody rises detected by the enzyme-linked immunosorbent assay. Furthermore, the assay was more sensitive than a neutralization assay. This enzyme-linked immunosorbent assay is an easy, accurate, and sensitive assay for measuring significant antibody rises to human coronavirus strain 229E group viruses, and it could be useful in the clinical diagnosis of these infections.",,"['Kraaijeveld, C A', 'Reed, S E', 'Macnaughton, M R']",,,,
,PMC,Influence of residual moisture and sealing atmosphere on viability of two freeze-dried viral vaccines.,,PMC273620,,,"This study demonstrated the complexity of the factors leading to changes in the infectivity titers of freeze-dried canine distemper and poultry infectious bronchitis viral vaccines. The change in moisture content during the storage period was an additional parameter which may influence the infectivity titer. The results emphasized the difficulty of predetermining variations in infectivity titers from the initial residual moisture. The analysis of the variations in infectivity titers during the storage of two vaccines led to the formulation of a hypothesis of the presence of two components of different thermostability. Moreover, the temporary increase in the infectivity titer of infectious bronchitis vaccine stored progressively dissociating during storage concurrent with a progressive inactivation of infectious particles.",,"['Precausta, P M', 'Simatos, D', 'Le Pemp, M', 'Devaux, B', 'Kato, F']",,,,
,PMC,The Prevention and Control of Epidemics of Acute Undifferentiated Diarrhea of Beef Calves in Western Canada,,PMC1789784,,,"It is frequently evident that outbreaks of diarrhea occur in spite of apparent “good management” and “good calving conditions”. This observation underlies the fact that we still do not understand many of the epidemiological factors which contribute to calf diarrhea outbreaks. For example, we still lack biological criteria by which to judge the degree of crowding and the degree of stress. Nevertheless, application of the principles described above will prevent or decrease the severity of many annual epidemics. To be successful, a program of prevention and control should be discussed with producers long before the calving season, preferably during the preceding summer or fall. Implementation of a complete program may take several calving seasons and producers should be made aware that prevention by improved management is an on-going, evolutionary process. More and improved vaccines are becoming available; however, as is the case with most biologicals, their impact cannot be determined until after they have been used for several years. They should be recognized as only one of several managent tools at the disposal of the veterinarian and livestock producer.",,"['Radostits, O. M.', 'Acres, S. D.']",,,,
,PMC,Infectivity of human coronavirus strain 229E.,,PMC273609,,,"The replication of human coronavirus strain 229E was observed by using indirect immunofluorescence in infected monolayers of MRC continuous cells. By 8 h after infection, bright cytoplasmic fluorescence was detected in cells infected with human coronavirus 229E. Discrete foci of infection were observed from 8 to 16 h after infection in cells infected with high dilutions of human coronavirus 229E; each fluorescent focus corresponded to a single virus infection. A fluorescent focus assay is described, using indirect immunofluorescence, which is more sensitive than the established techniques of tube titration and plaque assay. Particle/infectivity ratios for unpurified and purified virus preparations revealed a considerable drop in infectivity on purification.",,"['Macnaughton, M R', 'Thomas, B J', 'Davies, H A', 'Patterson, S']",,,,
,PMC,Rotavirus infection.,,PMC1146267,,,,,"['Wandless, I', 'Ions, V M', 'Evans, J G']",,,,
,PMC,Slow viruses and chronic disease: the contribution of epidemiology.,,PMC1422739,,,,,"Nathanson, N",,,,
,PMC,Pleural effusion disease agent as passenger of Treponema pallidum suspensions from rabbits. Survey of laboratories.,,PMC1045777,,,"Material from rabbits used for the propagation of Treponema pallidum in 12 selected laboratories was examined for a viral passenger agent of the treponemal suspensions. An agent which causes clinical or subclinical pleural effusion disease (PED) in rabbits and which is serologically identical or related to the PED agent isolated in Copenhagen was found as a contaminant in treponemal suspensions in laboratories in Europe, the USA, and Japan. The experience gained in the Scandinavian treponematoses laboratories suggests that strains of T pallidum contaminated with the PED agent can be purified by passage through hamsters.",,"['Fennestad, K L', 'Bruun, L', 'Wedø, E']",,,,
,PMC,Specific fluorescein-labeled antibodies to bovine viral diarrhea virus prepared from sera of rabbits immunized with purified virus.,,PMC1320084,,,"Specific fluorescein-labeled antibody conjugates to three strains of bovine virus diarrhea virus were prepared from hyperimmune rabbit sera. Viruses used to hyperimmunize the rabbits were purified by four different procedures. Conjugates were comparable in quality and specificity to conjugates prepared from serum of a calf hyperimmunized to bovine virus diarrhea virus in our laboratory. The latter conjugate was tested by Biologics Laboratories, National Veterinary Services, U.S.D.A., Ames, Iowa.",,"['Hart, R A', 'Rhodes, M B']",,,,
,PMC,Resistance to highly virulent mouse hepatitis virus acquired by mice after low-virulence infection: enhanced antiviral activity of macrophages.,,PMC551072,,,"As early as 1 to 2 days after intranasal inoculation with a mouse hepatitis virus of low virulence, MHV-S, susceptible DDD mice became fully resistant to a normally lethal challenge with a highly virulent MHV-2. The resistance of MHV-S-pretreated mice was correlated with significantly decreased MHV-2 multiplication in the liver, spleen, and brain. Infection with MHV-S did not induce a high level of interferon in DDD mice, and no neutralizing antibody against MHV-2 was detected in the sera of mice until day 6 of MHV-S infection. The multiplication of MHV-2 was suppressed in peritoneal cells (PC) in vivo and peritoneal adherent cells (PAC) in vitro of MHV-S-pretreated mice was compared with those of normal mice. This suppression of virus multiplication was demonstrated in PAC collected during days 1 to 3 of infection but not in PAC collected from day 5 on. PC from MHV-S-pretreated mice were also suppressive to MHV-2 growth in DK cells as compared with PC from normal mice. By treatment of MHV-S-pretreated mice with silica, suppression of virus growth in the liver was partially diminished. These findings suggest that increased suppression of MHV-2 growth in PAC (mostly macrophages) of MHV-S-pretreated mice is responsible for resistance.",,"['Taguchi, F', 'Yamada, A', 'Fujiwara, K']",,,,
,PMC,"Variables Affecting Local Immune Response in Ileal Loops: Role of Immunization Schedule, Bacterial Flora, and Postsurgical Inflammation",,PMC551043,,,"Several variables inherent in chronically isolated ileal (Thiry-Vella) loops in rabbits were studied for their effect on the local immune response of the intestine to live, locally invasive bacteria (Shigella X16). A much more vigorous local immunoglobulin A response to Shigella X16 was elicited when rabbits were immunized in their Thiry-Vella loops shortly after surgical creation of the loop than if a week were allowed to pass before they were immunized. Three major differences existed in Thiry-Vella loops on the day after surgery and a week later: (i) their microbial flora, (ii) nonspecific acute inflammation due to the surgery itself, and (iii) the histological appearance of the intestine. On day 1 after surgical creation of the Thiry-Vella loop, there were few bacteria in the loop, and the histology was that of normal small bowel except for mild acute inflammation due to the surgery. By day 6 after surgery, all loops contained large numbers of Pseudomonas aeruginosa and other aerobes, an atrophy of intestinal epithelium occurred, and the acute inflammation due to surgical trauma had subsided. By artificially colonizing Thiry-Vella loops with 10(8) or 10(10) live P. aeruginosa on the day of surgery, we found that the presence of these bacteria alone did not greatly diminish local immune responses to live Shigella. Furthermore, when the acute inflammation due to surgical trauma was recreated in loops 6 days old, no enhancement of the immune response was seen as compared to nontraumatized 6-day-old Thiry-Vella loops. The difference between immunization soon after surgery and a week later related to changes that occur in the loop itself with increased isolation. Finally, multiple immunizations of Thiry-Vella loops resulted in a more vigorous local immunoglobulin A response than a single immunization. These studies demonstrated that Thiry-Vella loop models can be useful in studying the kinetics of local immune responses by the intestine only if careful attention is paid to key variables inherent in the Thiry-Vella loop models themselves.",,"['Keren, D. F.', 'Holt, P. S.', 'Collins, H. H.', 'Gemski, P.', 'Formal, S. B.']",,,,
,PMC,Coronavirus Multiplication Strategy I. Identification and Characterization of Virus-Specified RNA,,PMC288755,,,"We examined the synthesis of intracellular RNA in primary chicken embryo kidney cells infected with the avian coronavirus infectious bronchitis virus. Infected cells were labeled with (32)P(i) in the presence of actinomycin D for the duration of the viral multiplication cycle, and nucleic acids were extracted, denatured, and analyzed on agarose slab gels. Six major RNA species were found. None of these RNAs was found in extracts of mock-infected cells. All six of the virus-specified RNAs (designated species A through F) were single stranded, and RNA species F had the same electrophoretic mobility as purified viral genome RNA. The molecular weights of the five subgenomic RNAs were estimated to be 0.8 × 10(6), 0.9 × 10(6), 1.3 × 10(6), 1.5 × 10(6), and 2.6 × 10(6) for species A through E, respectively. All of the RNAs were polyadenylated and are therefore likely to be viral mRNA's. The RNAs were synthesized in approximately constant proportions throughout the viral multiplication cycle. Intracellular RNA species A, B, C, D, and F and the purified viral genome were analyzed by RNase T(1) fingerprinting. The results confirmed the identification of RNA species F as the intracellular genome and the derivation of the four smaller RNAs from the genome. Fingerprinting also showed that the intracellular RNAs constitute a nested set such that the nucleotide sequence of each RNA is contained within all larger RNAs and each larger RNA contains an additional sequence congruent with its greater size. Finally, the possible modes of transcription and translation of the infectious bronchitis virus RNAs are discussed.",,"['Stern, David F.', 'Kennedy, S. Ian T.']",,,,
,PMC,Detection of virus particles by electron microscopy with polyacrylamide hydrogel.,,PMC1146115,,,"The use of lyphogel to concentrate the number of virus particles in specimens for electron microscopic examination was studied in parallel with ultracentrifugation. One hundred faecal and urine samples were compared. Both methods had a similar sensitivity. Lyphogel was economical, simple, and rapid in use; in contrast to ultracentrifugation, it required relatively little material. The procedure could be done within a safety cabinet, and virus particles were morphologically undamaged by the process.",,"['Whitby, H J', 'Rodgers, F G']",,,,
,PMC,Genome of porcine transmissible gastroenteritis virus.,,PMC288719,,,"The Purdue strain of transmissible gastroenteritis virus, a porcine coronavirus, was grown to titers of greater than 10(8) PFU/ml in a swine testicle cell line, and the RNA was isotopically labeled with [3H]uridine. The RNA was extracted from purified virus and was found to have the following properties. (i) It consisted primarily of a homogeneous large-molecular-weight species which electrophoretically migrated with an apparent molecular weight of 6.8 X 10(6) under denaturing conditions. (ii) It migrated electrophoretically at the same rate on nondenaturing gels before and after heat denaturation, suggesting that it does not consist of subunits. (iii) It was susceptible to pancreatic RNase A digestion in high (0.3 M) NaCl. (iv) It was polyadenylated to the extent that greater than 60% of the native RNA bound to oligodeoxythymidilic acid-cellulose under conditions of high (0.5 M) NaCl. RNA extracted from virions was infectious. This coronavirus can therefore be characterized as a positive-strand RNA virus.",,"['Brian, D A', 'Dennis, D E', 'Guy, J S']",,,,
,PMC,Does the major histocompatibility complex serve as a specific receptor for Semliki Forest virus?,,PMC288691,,,"Murine F9 and PCC4 teratoma cells do not express H-2 major transplantation antigens according to virus-specific T-lymphocyte cytotoxic or serological assays. However, such cells can be infected with and readily replicate many types of viruses (coxsackie B 3, mouse hepatitis, Sindbis, Semliki Forest [SFV], lymphocytic choriomeningitis, Pichinde, vesicular stomatitis, herpes simplex type 1) to the same extent as do murine F12 teratoma cells and mouse embryo fibroblasts, all of which express the H-2 determinants. In contrast, F9 and PCC4 cells are not productively infected with murine cytomegalovirus, whereas F12 and mouse embryo fibroblast cells are. In addition to replicating in H-2-negative murine teratoma cells, SFV replicates in H-2-negative murine lymphoblastoid cells. The ability of SFV to infect cells without H-2 antigens and then to effect viral antigenic expression in the cells' cytoplasm and on their surface with similar kinetics and in equivalent amounts as cells with H-2 antigens indicates that the H-2 receptor is not needed for SFV infection. Daudi cells, which lack HLA antigens, block the replication of SFV. This occurs at some point after receptor binding, as demonstrated by diminished viral mRNA. In addition, a possible membrane defect precludes viral exit in Daudi cells transfected with SFV infectious RNA. These results indicate that a cell's possession of H-2 antigens is not a requirement for SFV infection and that major histocompatibility complex antigens are not specific receptors for this virus.",,"['Oldstone, M B', 'Tishon, A', 'Dutko, F J', 'Kennedy, S I', 'Holland, J J', 'Lampert, P W']",,,,
,PMC,Micro-organisms in outpatient infantile gastroenteritis.,,PMC1626768,,,"This study reports the results of an examination of the stools of 58 infants with gastroenteritis who were seen as outpatients. The stools were examined by routine bacterial culture, and by electron microscopy for virus particles. The stools of a comparable control group of infants who had no gastrointestinal symptoms were also similarly examined. Enteropathogenic Escherichia coli, Salmonella sp., and rotaviruses, as well as other viruses, particularly adenoviruses and coronaviruses, were isolated.",,"['Weindling, A M', 'Walker-Smith, J A', 'Bird, R']",,,,
,PMC,Coronavirus-like particles associated with diarrhea in baby pigs in Quebec.,,PMC1789692,,,,,"['Turgeon, D C', 'Morin, M', 'Jolette, J', 'Higgins, R', 'Marsolais, G', 'DiFranco, E']",,,,
,PMC,Intestinal coccidiosis in baby pig diarrhea.,,PMC1789683,,,,,"['Robinson, M M', 'Turgeon, D']",,,,
,PMC,Rapid diagnosis by electron microscopy of nonbacterial gastroenteritis in children.,,PMC1801758,,,,,"['Blaskovic, P. J.', 'Kuderewko, O.', 'McLaughlin, B.', 'Yong, D. C.', 'Ball, F. R.']",,,,
,PMC,Infectious diarrhea: clinical implications of recent research.,,PMC1801608,,,,,"Hamilton, J. R.",,,,
,PMC,Approches applicables à la lutte contre les maladies respiratoires à virus.,,PMC2395985,,,,,"Tyrrell, D. A.",,,,
,PMC,Approaches to the control of respiratory virus diseases,,PMC2395940,,,"Viruses of various biological types are known to cause a wide range of acute respiratory infections, ranging from mild colds and catarrh to severe bronchiolitis and pneumonia. Bacteria also cause respiratory diseases including serious conditions such as otitis media and pneumonia. The whole situation is complex and to understand the epidemiology we also need to consider nutrition, environment, climate, and chronic diseases. Acute respiratory viral diseases are very common in all areas of the world and contribute to morbidity and probably to mortality. There are no antiviral drugs or vaccines which would be generally useful. It ought to be possible to reduce the effects of these diseases by improving the standard of general management of cases. This would involve careful nursing, administration of appropriate antibiotics, and referral of severe cases to a properly staffed and equipped hospital. Further research is needed to develop ways of doing this and to evaluate the results.",,"Tyrrell, D. A. J.",,,,
,PMC,Diarrhées à rotavirus et autres diarrhées virales,,PMC2395939,,,,,,,,,
,PMC,Détection des antigènes et des anticorps IgM pour le diagnostic rapide des infections virales: Mémorandum OMS,,PMC2395912,,,,,,,,,
,PMC,Rotavirus and other viral diarrhoeas,,PMC2395787,,,"Recent evidence indicates that viruses are an important cause of acute diarrhoea in infants and young children in both developed and developing countries. This article reviews the available information on the epidemiology, clinical features, and laboratory diagnosis of acute diarrhoea due to two of the more important and recently discovered viruses, namely rotaviruses and the Norwalk and Norwalk-like agents, or to other viral agents. Research priorities are also recommended that will help to elucidate the epidemiology, pathophysiology, and means of preventing viral diarrhoeas. Foremost among these research priorities is the development of a rotavirus vaccine for use in man.",,,,,,
,PMC,Canine Enteritis Associated with a Hemagglutinating Virus,,PMC1789660,,,A fatal case of hemorrhagic enteritis in a young dog is described. Hemagglutination and electron microscopic studies support a viral etiology.,,"Lynch, J. A.",,,,
,PMC,Isolation of coronavirus envelope glycoproteins and interaction with the viral nucleocapsid.,,PMC288560,,,"The two envelope glycoproteins and the viral nucleocapsid of the coronavirus A59 were isolated by solubilization of the viral membrane with Nonidet P-40 at 4 degrees C followed by sucrose density gradient sedimentation. Isolated E2 consisted of rosettes of peplomers, whereas E1, the membrane glycoprotein, was irregular and amorphous. Under certain conditions significant interactions occurred between components of Nonidet P-40-disrupted virions. Incubation of the Nonidet P-40-disrupted virus at 37 degrees C resulted in formation of a complex between one of the viral glycoproteins, E1, and the viral nucleocapsid. This was caused by a temperature-dependent conformational change in E1, resulting in aggregation of E1 and interaction with the viral RNA in the nucleocapsid. E1 also bound rRNA. The E1-nucleocapsid complexes can be distinguished on sucrose and Renografin density gradients from native viral nucleocapsids. The separation of the membrane glycoprotein E1 from the peplomeric glycoprotein E2 permitted preparation of antisera against these isolated proteins. A model is proposed for the arrangement of the three major structural proteins in the coronavirus A59 virion in relation to the viral envelope and RNA.",,"['Sturman, L S', 'Holmes, K V', 'Behnke, J']",,,,
,PMC,Coronavirus JHM: Cell-Free Synthesis of Structural Protein p60,,PMC288519,,,"Sac(-) cells infected with murine coronavirus strain JHM shut off host cell protein synthesis and synthesized polypeptides with molecular weights of 150,000, 60,000, and 23,000. The 60,000- and 23,000-molecular-weight polypeptides comigrated with virion structural proteins p60 and p23, and the 60,000-molecular-weight protein was identified as p60 by tryptic peptide fingerprinting. Polyadenylate-containing RNA [poly(A) RNA] extracted from the cytoplasm of infected cells directed the synthesis of both 60,000- and 23,000-molecular-weight polypeptides in messenger-dependent cell-free systems derived from mouse L-cells and rabbit reticulocytes. The reticulocyte system also synthesized a 120,000-molecular-weight polypeptide that was specifically immunoprecipitated by antiserum raised against JHM virions. The identity of the 60,000- and 23,000-molecular-weight in vitro products was established by comigration with virion proteins, immunoprecipitation, and in the case of p60, tryptic peptide fingerprinting. The cytoplasmic poly(A) RNAs which encoded p60 and p23 sedimented in sucroseformamide gradients at 17S and 19S, respectively, and were clearly separable. These RNAs were among the major poly(A) RNA species synthesized in the cytoplasm of actinomycin D-treated cells late in infection, and the in vitro translation of size-fractionated RNA released from polysomes confirmed that they represent physiological mRNA's. These results suggest that the expression of the coronavirus JHM genome involves more than one subgenomic mRNA.",,"['Siddell, Stuart G.', 'Wege, Helmut', 'Barthel, Andrea', 'ter Meulen, Volker']",,,,
,PMC,Infection of cultured human type II pneumonocytes with certain respiratory viruses.,,PMC414663,,,"Human type II alveolar pneumonocytes were grown either as monolayers derived from a clone or as organotypic cultures of fetal lung. The type II cells in these cultures retained in their cytoplasm multilamellar bodies which were morphologically identical to similar organelles present in type II cells of intact human fetal and adult lung. A number of respiratory viruses infected the cells and produced a cytopathic effect in the cultures. Viral components were also detected in some of the infected cells. Adenovirus type 3, human coronavirus 229E, and rhinovirus types 2 and 9 produced new infectious virus, but influenza A and parainfluenza 3 virus apparently did not.",,"['Tyrrell, D A', 'Mika-Johnson, M', 'Phillips, G', 'Douglas, W H', 'Chapple, P J']",,,,
,PMC,"Virus-like particle, 35 to 40 nm, associated with an institutional outbreak of acute gastroenteritis in adults.",,PMC273256,,,"In an outbreak of acute gastroenteritis in an institution for the mentally retarded at Otofuke, Hokkaido, Japan, virus-like particles were observed by electron microscopy in five of seven stool specimens from the patients. The particles had 10 rod-shaped and 10 round projections or capsomeres on the periphery, measured 35 to 40 nm in diameter, and had a buoyant density of 1.35 to 1.37 g/ml in cesium chloride. Attempts to culture these particles in tissue culture or in mouse brain were unsuccessful. Immune electron miscroscopy performed with the virus from the patients as antigen demonstrated significant serological responses in all patients examined. Antigenic similarity of the virus particles obtained from five patients was also confirmed by immune electron microscopy with the paired acute- and convalescent-phase sera of one of the patients. Furthermore, in immune electron micrsocopy these particles appeared to have no antigenic relationship to three candidate viruses for gastroenteritis so far reported: the Norwalk agent, the W agent, and the calicivirus-like particle. These results suggested the possibility that this agent, tentatively designated as the Otofuke agent, might be a new candidate virus for gastroenteritis.",,"['Taniguchi, K', 'Urasawa, S', 'Urasawa, T']",,,,
,PMC,Phosphoproteins of murine hepatitis viruses.,,PMC353599,,,Four strains of the coronavirus murine hepatitis virus were examined for the presence of phosphorylated proteins. The nucleocapsid protein was determined to contain phosphate covalently linked to serine but not to threonine residues. The nucleocapsid protein was the only phosphorylated protein detected in these strains of murine hepatitis virus.,,"['Stohlman, S A', 'Lai, M M']",,,,
,PMC,Viruses and acute abdominal pain in childhood.,,PMC1545643,,,"Children aged at least 4 years admitted to hospital with acute abdominal pain, excluding appendicitis, were investigated for the presence of viruses. Out of 181 children 29 were found with viruses of whom 18 had nonspecific abdominal pain. Eight others were found to have virus-like particles on electron microscopical examination of their faeces. Virus infections contribute to a small extent to nonspecific abdominal pain in childhood, but in many cases the cause remains unknown.",,"['Pullan, C R', 'Halse, P C', 'Sims, D G', 'Alexander, F W', 'Gardner, P S', 'Codd, A A']",,,,
,PMC,Bovine Fetal Inoculations with Calf Rotavirus,,PMC1320013,,,"The serological and histopathological responses of bovine fetuses to in utero inoculation with virulent and attenuated strains of the calf rotavirus (reovirus-like agent of neonatal calf diarrhea) are described. Thirteen bovine fetuses, 63 to 190 days of gestation, were inoculated in utero with attenuated (three fetuses) or field strain virus (nine fetuses) or both (one fetus). Serum-neutralizing antibody titers ranging from 1:16 to > 1:256 were detected in six of eight fetuses tested, demonstrating the ability of the bovine fetus to respond immunologically to this agent. The youngest fetus in the series was inoculated at 63 days of gestation and developed a titer of 128 in 64 days. This represents the earliest stage of gestation at which a bovine fetus has been inoculated with a bovine virus and found to produce antibody to it. Serum neutralizing titers in six of the eight dams tested increased significantly following the inoculations of their fetuses in utero. Histological changes associated with viral replication and antigenic stimulation of the lymphoreticular system were observed. Pneumonic lesions consisting of both local and diffuse lymphoreticular proliferation were present in five of the nine fetuses that were alive at slaughter. Gliosis and perivascular cuffing were noted in the brains of two of these fetuses and meningitis was seen in one. No evidence of teratogenic change was found.",,"['Schlafer, D. H.', 'Schultz, R. D.', 'Scott, F. W.', 'Duncan, J. R.']",,,,
,PMC,Enzyme-linked immunosorbent assay for detection of antibodies to murine hepatitis virus.,,PMC273223,,,An enzyme-linked immunosorbent assay was developed for the detection of antibodies to murine hepatitis virus. A high prevalence of antibody to murine hepatitis virus was found by the enzyme-linked immunosorbent assay in colonies with a low prevalence of complement-fixing antibodies. Murine hepatitis virus strain A59 was found to be broadly reactive as an enzyme-linked immunosorbent assay antigen.,,"['Peters, R L', 'Collins, M J', ""O'Beirne, A J"", 'Howton, P A', 'Hourihan, S L', 'Thomas, S F']",,,,
,PMC,Counterimmunoelectroosmophoresis for detection of neonatal calf diarrhea coronavirus: methodology and comparison with electron microscopy.,,PMC273137,,,"A counterimmunoelectroosmophoresis (CIE) technique is described for the detection of calf diarrhea coronavirus antigens in intestinal contents. The antibody reagent was prepared in rabbits against the Nebraska calf diarrhea coronavirus adapted to Vero cells and purified by density gradient centrifugation. The method was applied to intestinal contents of diarrheic and normal calves and compared with electron microscopy (EM). Calf coronavirus antigens were detected in intestinal contents of 44% (21/48) of the diarrheic calves and 24% (4/17) of the normal calves. Two precipitin lines could be observed in the majority of the positive samples. When compared with EM, CIE detected more positive animals. In only two cases (2/20) CIE was negative despite the visualization of coronavirus particles by EM.",,"['Dea, S', 'Roy, R S', 'Begin, M E']",,,,
,PMC,Use of electron microscopy and an enzyme-linked immunosorbent assay for the detection of rotaviruses in neonatal calf diarrhea.,,PMC1319897,,,Electron microscopy and an enzyme-linked immunosorbent assay were compared for the diagnosis of rotaviruses associated with neonatal calf diarrhea. One hundred percent correlation was observed when 125 samples were tested by both techniques. Both techniques were equally efficient in detecting rotaviruses. The enzyme-linked immunosorbent assay was more sensitive but being specific could not detect other viruses.,,"['Payment, P', 'Marsolais, G', 'Trudel, M', 'Fauvel, M', 'Lamontagne, L', 'Assaf, R', 'Marois, P']",,,,
,PMC,The indirect fluorescent antibody technique as a method for detecting antibodies in aborted fetuses.,,PMC1319888,,,"In this investigation the indirect fluorescent antibody technique was used to titrate antibodies in bovine sera to parainfluenza 3, infectious bovine rhinotracheitis virus and bovine viral diarrhea virus. These results were compared to those determined on the same samples by hemagglutination inhibition for parainfluenza 3 virus and serum neutralization for bovine virus diarrhea and infectious bovine rhinotracheitis virus. The results of the serological methods agreed closely. The indirect fluorescent antibody technique is a rapid and sensitive method for detecting antibodies and the procedure lends itself to use in diagnostic laboratories. In addition to the above viruses the presence or absence of antibodies to bovine coronavirus and bovine adenovirus 3 were determined by the indirect fluorescent antibody technique in thoracic fluids from 100 aborted fetuses and 50 nonaborted fetuses. Results on these samples were not compared to hemagglutination inhibition or serum neutralization as the condition of fluid samples from aborted fetuses renders interpretation of such tests unreliable. Antibodies to one or more viruses were detected in 30 of the 100 aborted fetuses and in seven of the 50 nonaborted fetuses. Antibodies to more than one agent were detected in eleven of the 100 aborted and in one of the 50 nonaborted fetuses. Reasons for this occurrence and application of the test in determination of causes of abortion are discussed.",,"['Miller, R B', 'Wilkie, B N']",,,,
,PMC,"Comparison of electron microscopy, enzyme-linked immunosorbent assay, solid-phase radioimmunoassay, and indirect immunofluorescence for detection of human rotavirus antigen in faeces.",,PMC1145778,,,"Four techniques were compared for their practicability, speed, and sensitivity for the detection of human rotavirus. Radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) were found to be the most sensitive means of identifying rotavirus, and, once processed, up to 40 specimens could be examined daily. Electron microscopy, although less sensitive than these techniques, had the advantage of being able to detect other viral agents present in faecal extracts. Indirect immunofluorescence failed to detect rotavirus as often as the other three methods. In laboratories where routine examination of faecal specimens from patients with gastroenteritis is required, ELISA and RIA are useful alternatives to electron microscopy.",,"['Birch, C J', 'Lehmann, N I', 'Hawker, A J', 'Marshall, J A', 'Gust, I D']",,,,
,PMC,Rabbit cardiomyopathy associated with a virus antigenically related to human coronavirus strain 229E.,,PMC2042305,,,"A new disease of rabbits is described. Following an acute febrile course, animals die or recover by the 11th day postinoculation. The characteristic pathologic finding is multifocal myocardial degeneration and necrosis. The disease can be transmitted by various routes with tissue filtrates or with infectious sera diluted to 10(-6) and passed through 0.1 micron filters. Virus particles with morphologic features characteristic of a coronavirus are present in infectious but not in normal rabbit serums. The antigen(s) in the infectious serums cross-reacts with the 229E and the OC43 strains of human coronavirus. Antigen cross-reacting with the 229E virus is detectable by immunofluorescent staining in frozen sections of heart tissue from sick but not from healthy animals. Animals surviving infection seroconvert to coronavirus specificity, as demonstrated by the presence in convalescent serums of antibody capable of reacting with the 339E virus. Susceptibility to infection has not been demonstrated in mice, hamsters, or guinea pigs, and the virus was not adapted for growth in tissue culture. It is uncertain whether the agent is a natural pathogen of rabbits or a coronavirus contaminant from another species, possibly human. The name rabbit infectious cardiomyopathy is suggested for this disease.",,"['Small, J. D.', 'Aurelian, L.', 'Squire, R. A.', 'Strandberg, J. D.', 'Melby, E. C.', 'Turner, T. B.', 'Newman, B.']",,,,
,PMC,Plaque assay and improved yield of human coronaviruses in a human rhabdomyosarcoma cell line.,,PMC275387,,,"Propagation and plaque assay of human coronavirus prototypes were studied in two human cell lines: a diploid fetal tonsil (FT) and a heteroploid rhabdomyosarcoma (RD) cell lines. Plaques, observed within 2 to 3 days on FT cell monolayers with both 229E and OC43 viruses, appeared as colorless areas after staining with neutral red or crystal violet, whereas neutral red staining was required for visualization of plaques on RD cells. The plating efficiencies were approximately equal between the two cell lines, but virus assay by plaque formation was 15- to 30-fold more efficient than tube dilution assay with 50% endpoints. The discrepancy between 50% endpoint and plaque-forming unit values was striking and appeared to result from the fact that killing of cells (particularly RD cells) by coronaviruses was not accompanied by visible changes in the cells but killing was detected by the failure of infected cells to stain with a vital dye. The latent phase in one-step growth curves was 5 to 6 h for both viruses in either cell line, but the maximum yield of intracellular virus was reached in 18 to 20 h for FT cells and 24 to 28 h for RD cells. Virus release also differed between the two cell lines: in FT cells, the maximum yield of extracellular virus was reached 2 to 3 h later than that of intracellular virus, whereas in RD cells, the difference was 5 h for 229E virus and 10 h for OC43 virus. Although both cell lines appear equally useful for plaque assay, RD cells would be preferred for mass virus propagation because yields (5 X 10(8) plaque-forming units per ml) were 10-fold higher than in FT cells, a finding true for both virus prototypes.",,"['Schmidt, O W', 'Cooney, M K', 'Kenny, G E']",,,,
,PMC,A year's experience of the rotavirus syndrome and its association with respiratory illness.,,PMC1545549,,,"In a hospital study rotavirus was identified in 51% of 152 children with diarrhoea. These patients showed a clinical pattern that was distinct from patients in whom the diarrhoea was associated with bacteria, other viruses, or no pathogens. A respiratory illness was described in 66% of rotavirus patients and usually preceded the gastrointestinal symptoms. Vomiting lasted between one and 3 days and was curtailed by substituting the normal diet with clear fluids. Watery diarrhoes continued for 4 or 5 days, even when rehydration was by the intravenous rather than the oral route. Prolonged diarrhoea was rare. Most children infected with rotavirus were under 2 years of age, but dehydration was most severe in infants aged between 12 and 18 months. A clinician can thus recognise the rotavirus syndrome and expect spontaneous recovery if adequate rehydration is maintained for a critical few days.",,"['Lewis, H M', 'Parry, J V', 'Davies, H A', 'Parry, R P', 'Mott, A', 'Dourmashkin, R R', 'Sanderson, P J', 'Tyrrell, D A', 'Valman, H B']",,,,
,PMC,New strain of mouse hepatitis virus as the cause of lethal enteritis in infant mice.,,PMC414330,,,"A new strain of mouse hepatitis virus (MHV) was isolated from pooled gut suspensions from an epizootic of lethal enteritis in newborn mice. Negative-contrast electron microscopy showed an abundance of coronavirus particles in the intestinal contents and intestinal epithelium of moribund mice. We found no other virus in the epizootic. Dams seroconverted to MHV polyvalent antigen and to the agent isolated, but did not develop antibodies to other known mouse pathogens. Virus propagated in NCTC-1469 tissue culture produced enteric disease in suckling mice but not fatal diarrhea; the dams of these mice also developed antibodies to MHV and to the isolates. By complement fixation, single radial hemolysis, and quantal neutralization tests, we found the isolates antigenically most closely related to MHV-S, unilaterally related to MHV-JHM, and more distantly related to MHV-1, MHV-3, MHV-A59, and human coronavirus OC-43. We also studied cross-reactions among the murine and human coronaviruses in detail. Tissues of infected newborn mice were examined by light microscopy, thin-section electron microscopy, and frozen-section indirect immunofluorescence, revealing that viral antigen, virus particles, and pathological changes were limited to the intestinal tract. We have designated our isolates as MHV-S/CDC.",,"['Hierholzer, J C', 'Broderson, J R', 'Murphy, F A']",,,,
,PMC,Effect of mouse hepatitis virus infection on iron retention in the mouse liver.,,PMC2041433,,,"Increased iron uptake and iron-induced ferritin synthesis has been demonstrated in experimentally virus-infected cell cultures. However, this has not been observed in the intact animal. The results reported in this paper indicate that higher deposition of injected radioiron occurs in the livers of mice infected with MHV-3 virus compared with livers from uninfected animals. Administration of iron at different time intervals indicated that iron uptake correlates well with the degree of tissue injury in the livers of infected animals.",,"['Tiensiwakul, P.', 'Husain, S. S.']",,,,
,PMC,"Characterization of EV-2, a Virus Isolated from European Eels (Anguilla anguilla) with Stomatopapilloma",,PMC353329,,,"A virus designated EV-2 has been isolated from external tumor tissue and internal organs of European eels (Anguilla anguilla) with stomatopapilloma. It contains RNA and is ether, acid, and temperature labile above 4°C, and concentrated preparations agglutinate chicken and sheep erythrocytes. The addition of actinomycin D during the first 2.75 h of infection inhibits viral replication. As determined in sucrose gradients, the buoyant density of the virus is 1.19 g/cm(3). EV-2 has a moderately pleomorphic spherical morphology; its diameter ranges from 80 to 140 nm. The virion has narrow, regularly spaced surface projections about 10 nm long. Replication in FHM cells at 15°C shows new infectivity appearing at 10 h postinfection and reaching a plateau at 20 h. Cytopathic effects consist of cell fusion, syncytia, and irregularly rounded cell masses. Viral antigen was detected in the cytoplasm of infected cells by specific immunofluorescence.",,"['Nagabayashi, Toshihiko', 'Wolf, Ken']",,,,
,PMC,Acute nonbacterial gastroenteritis. Animal model: acute enteritis in dogs infected with coronavirus.,,PMC2042245,,,,,"['Keenan, K. P.', 'Binn, I. N.', 'Takeuchi, A.']",,,,
,PMC,Lymphocyte Proliferative Response to Viral Antigen in Pigs Infected with Transmissible Gastroenteritis Virus,,PMC414154,,,"Development and sequence of lymphocytes reactive to viral antigen in Peyer's patches, mesenteric lymph nodes, spleen, and peripheral blood of pigs orally inoculated with transmissible gastroenteritis virus were investigated by a lymphocyte proliferative assay. Lymphocytes reactive to the viral antigen were first detected in all the tissues of pigs tested on postinoculation day 7. Thereafter, they increased in proliferative reactivity and reached a maximal amount on postinoculation days 10 to 14. Antigen-reactive cells were persistently demonstrated in Peyer's patches and mesenteric lymph nodes for at least 110 days after inoculation, although lymphocytes decreased a little in reactivity to the viral antigen with the lapse of time. On the other hand, splenic and peripheral blood cells were found to have only transient proliferative reactivity. No antigen-reactive cells were detected in spleen or peripheral blood after postinoculation days 20 to 30. Lymphocytes decreased remarkably in reactivity to the viral antigen and phytohemagglutinin when treated with anti-porcine thymocyte serum and complement. Their reactivity to lipopolysaccharides was hardly affected by the treatment. Cells harvested on postinoculation days 45 to 60, however, responded a little to the viral antigen even after they were treated with anti-porcine thymocyte serum and complement. Lymphocytes reactive to the viral antigen and phytohemagglutinin belonged mainly to the erythrocyte rosette-forming cell fraction, whereas those reactive to lipopolysaccharides were mostly found in the rosette-nonforming cell fraction.",,"['Shimizu, Mitsugu', 'Shimizu, Yukio']",,,,
,PMC,The human enteric coronaviruses.,,PMC2425376,,,"A coronarirus was seen in the faeces from 15 (4.2%) of 355 adults with diarrhoea and from 5 (5.2%) of 96 adults without diarrhoea. Similar particles were seen in the faeces from 5 (2.2%) of 227 children aged 1--14 years with gastroenteritis, but in none of those from 230 infants under one year of age with gastroenteritis. There was no evidence that the coronavirus was responsible for any of 34 outbreaks of gastroenteritis, although it possibly caused diarrhoea in patients admitted to a psycho-geriatric unit. Excretion of the virus often continued for many months. One strain was propagated in human embryo kidney monolayers and human embryo intestinal organ cultures, although serial passage could not be accomplished.",,"['Clarke, S. K.', 'Caul, E. O.', 'Egglestone, S. I.']",,,,
,PMC,"Studies of rhinoviruses and coronaviruses at the Common Cold Unit, Salisbury, Wiltshire.",,PMC2425374,,,,,"Tyrrell, D. A.",,,,
,PMC,Medicine and Books,,PMC1597530,,,,,,,,,
,PMC,The calf reo-like virus (rotavirus) vaccine: an ineffective immunization agent for rotaviral diarrhea of piglets.,,PMC1319944,,,"Rotavirus, in a commercially available calf vaccine, did not replicate in newborn colostrum-free piglets inoculated orally with one half of a calf dose. Gross and microscopic examination of these vaccinated piglets revealed no lesions consistent with rotaviral infection and vaccinated piglets were susceptible to challenge by porcine rotavirus. Challenged piglets vomited, had diarrhea and became severely dehydrated. Rotavirus was visualized in their gut fluid. Villi in the small intestines were shortened, blunted and fused. Rotaviral antigens were seen in enterocytes.",,"['Lecce, J G', 'King, M W']",,,,
,PMC,"Comparison of results using electron microscope, immunodiffusion and fluorescent antibody analyses to detect rotavirus in diarrheic fecal samples of calves.",,PMC1319943,,,"Seventy-nine diarrheic calf fecal samples were examined by electron microscopy, immunodiffusion and the fluorescent antibody technique for the presence of rotavirus (reovirus-like agent). Thirty-eight (48%) of the samples were positive by electron microscopy, 59% by immunodiffusion and 20% positive by fluorescent antibody technique analyses. Another 9% were suspect-positive by fluorescent antibody technique. Chymotrypsin treatment of the fecal samples increased the ease of observing the viral particles by electron microscopy and also intensified the immunodiffusion arcs obtained. Immunodiffusion analyses using specific antisera to the virus would appear to be a practical method of detecting rotavirus in diarrheic fecal samples.",,"['Rhodes, M B', 'Stair, E L', 'McCullough, R A', 'McGill, L D', 'Mebus, C A']",,,,
,PMC,Viruses in the stools.,,PMC1145558,,,"It has long been possible to isolate viruses from the stools by culture, though the viruses found are rarely implicated in disease of the gut. In contrast, only recently has it been possible to identify viruses in the stools of patients with diarrhoea. Initially, such identifications were made by electron microscopy but the unsuitability of the microscope for large-scale screening has led to the development of other methods. The new methods have concentrated on rotaviruses but other viruses are also implicated and an overall view of the significance of finding a virus in any stool specimen has to take into account the evidence about all viruses, old and new.",,"Madeley, C R",,,,
,PMC,Inhibition of coronavirus 229E replication by actinomycin D.,,PMC353142,,,"The yields of human coronavirus 229E grown in L132 cells were markedly inhibited by actinomycin D, the 50% inhibitory dose being 0.1 micron/ml. Inhibition was maximal during the early phase of virus replication, did not appear to involve viral RNA synthesis per se, and was shown to be dependent on the input multiplicity of infection.",,"['Kennedy, D A', 'Johnson-Lussenburg, C M']",,,,
,PMC,Bovine coronavirus genome.,,PMC353118,,,"The tissue culture-adapted strain (Mebus) of the bovine coronavirus was grown to titers of greater than 10(7) 50% tissue culture infective doses per ml in secondary bovine embryo kidney cells, and the RNA was isotopically labeled with [3H]uridine. The RNA was extracted from purified virus and was found to have the following properties. (i) It consisted primarily of a homogeneous large-molecular-weight species which comigrated electrophoretically with vesicular stomatitis viral RNA and therefore had an apparent molecular weight of 3.8 X 10(6). (ii) It remained as a 3.8 x 10(6)-molecular-weight molecule after heat denaturation when rapidly harvested virus was examined. (iii) It was 80% susceptible to pancreatic RNase A digestion in high (0.3 M) NaCl, and the 20% resistant fraction was 4S to 7S in size. (iv) It was polyadenylated to the extent that 40 and 60% of the native RNA bound to polyuridylic acid-Sepharose and oligodeoxythymidylic acid-cellulose, respectively, under conditions of high (0.5 M) NaCl.",,"['Guy, J S', 'Brian, D A']",,,,
,PMC,Canine gastroenteritis associated with a parvovirus-like agent.,,PMC1789433,,,,,"['Thomson, G W', 'Gagnon, A N']",,,,
,PMC,The use of immunofluorescence techniques for the laboratory diagnosis of transmissible gastroenteritis of swine.,,PMC1277661,,,"Over a four year period, 74 of 250 field outbreaks of enteric disease (30%) and 110 of 440 swine (25%) were positive for transmissible gastroenteritis by immunofluorescence procedures. Of 141 swine from herds positive for transmissible gastroenteritis 110 (78%) were positive by fluorescent antibody techniques. The fastest, easiest to perform and most effective procedure was the examination of frozen sections of the jejunum from acutely ill animals by the fluorescent antibody tissue section technique. Only two herds were found to be positive by the fluorescent antibody tissue culture technique which were negative by fluorescent antibody tissue section technique. A considerable number of outbreaks, 21 of 74 (28%), of transmissible gastroenteritis were detected by immunofluorescence in swine over two weeks of age. The majority of outbreaks of transmissible gastroenteritis, 50 of 74 (68%), occurred in Missouri during the months of January through April and 63 of 74 (85%) during the months of December through May. The recurrence of the disease in a number of counties over a four-year period suggest the possibility of endemic foci.",,"['Solorzano, R F', 'Morin, M', 'Morehouse, L G']",,,,
,PMC,The postulated role of feeder swine in the perpetuation of the transmissible gastroenteritis virus.,,PMC1277660,,,"Clinical, immunofluorescence and histopathological observations were found to be an efficient approach for the confirmation of the diagnosis of transmissible gastroenteritis in feeder swine. Two cases are reported to exemplify how feeder swine exposed to points of concentration such as holding areas, sales barns and auctions can play an important role in the epizootiology of transmissible gastroenteritis. A third field case is reported as an example of an outbreak of transmissible gastroenteritis beginning in feeder swine and then spreading to baby pigs on the farm. All baby pigs died that were born during the acute phase of the outbreak in the feeder swine. Baby pigs born shortly after the clinical signs had abated in the herd, and from sows that had been exposed orally to virulent transmissible gastroenteritis virus and vaccinated with a commercial transmissible gastroenteritis vaccine ten days before farrowing, survived. This was explained by a combination of a decrease in the amount of virus shed in the environment and the immunity induced in the sows. These observations of field outbreaks of transmissible gastroenteritis combined with recently reported experimental studies lend strong support to the hypothesis of a reservoir for transmissible gastroenteritis virus in feeder pigs. This reservoir would be based principally on the transmission of the virus on a continuous basis from the feces of recently infected pigs to susceptible pigs. Clinical signs of transmissible gastroenteritis in such pigs are difficult to recognize or absent and this contributes to the importance of the reservoir in the field.",,"['Morin, M', 'Solorzano, R F', 'Morehouse, L G', 'Olson, L D']",,,,
,PMC,Enzyme-linked immunosorbent assay determination of specific rubella antibody levels in micrograms of immunoglobulin G per milliliter of serum in clinical samples.,,PMC275263,,,"A ""microgram assay"" is described in which solid-phase enzyme-linked immunosorbent assay is used for the determination of specific rubella immunoglobulin G (IgG) antibody levels in micrograms per milliliter of serum. The quantitation was based on a standard curve obtained by using a reference serum, for which the specific IgG content was assayed by immunochemical purification. IgG was first purified and specific rubella antibodies were separated by an immunoadsorbent prepared by linking rubella virus antigens to Sepharose 4B. By using IgG-specific conjugate, the levels of specific rubella IgG antibodies could then be determined from clinical samples. Seronegative samples showed antibody levels less than 1 microgram/ml, whereas levels up to several hundred micrograms per milliliter were detected in some postinfection sera. The correlation between microgram antibody levels and hemagglutination inhibition titers was linear. The method offers a simple and sensitive antibody assay which could be used both for the laboratory diagnosis of acute rubella and for the evaluation of immunity.",,"['Leinikki, P O', 'Shekarchi, I', 'Dorsett, P', 'Sever, J L']",,,,
,PMC,Plastic multiwell plates to assay avian infectious bronchitis virus in organ cultures of chicken embryo trachea.,,PMC275257,,,"Simple assay systems for infectivity titrations of avian infectious bronchitis virus (IBV) in chicken embryo trachea organ cultures (OC) were developed using plastic multiplate wells with one tracheal ring per well; these assays appeared to be much more satisfactory than the conventional rolled-tube method. The medium, 0.05 M HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid)-buffered Eagle minimal essential medium was not changed during observation. A medium containing 0.4% bovine serum albumin did not influence the virus yield, but did stabilize virus viability during storage. Reproducibility of results obtained in the OC system was confirmed by performing replicate titrations of the Beaudette strain with three different passage histories. The mean virus titers in the OC were lower than those in chicken embryos, depending on the IBV passage histories. The time required for ciliostasis was related not only to the concentration of virus, but also to the IBV passage history. Application of OC techniques for the constant serum-variable virus neutralization test gave low neutralization indexes with excellent reproducibility as compared with those obtained in the chicken embryo assay system. Also, the slopes of neutralization curves obtained by assays in OC were less steep than those seen in the chicken embryo system.",,"['Yachida, S', 'Aoyama, S', 'Takahashi, N', 'Iritani, Y', 'Katagiri, K']",,,,
,PMC,Astrovirus-associated gastroenteritis in children.,,PMC1145456,,,"In a small astrovirus-associated outbreak of gastroenteritis in a ward of a local children's hospital two out of five children with symptoms excreted astrovirus particles. No astrovirus particles were found in faeces from the remaining asymptomatic child, and no other viral or bacterial pathogens were found in any of the children. Virus excretion persisted for only a few days. Rising antibody titres to the astrovirus particles were demonstrated in one child, and IgM was also demonstrated in this patient's serum.",,"['Ashley, C R', 'Caul, E O', 'Paver, W K']",,,,
,PMC,"Isolation of animal viruses from farm livestock waste, soil and water.",,PMC2129775,,,"Ten porcine enteroviruses, 2 porcine adenoviruses and 1 coronavirus were isolated directly from 32 samples of slurry collected from a pig fattening house. Concentration of the same samples by adsorption with the polyelectrolyte PE-60 yielded 24 porcine enteroviruses and 3 porcine adenoviruses. A porcine enterovirus was isolated, following PE-60 concentration, from 1 to 6 slurry samples from a sow farrowing house. No virus was isolated from 12 samples of slurry from dairy cows nor from 6 slurry samples from a calf-rearing unit. A porcine enterovirus was isolated from soil samples, after concentration with PE-60, collected 1, 2 and 8 days after pig slurry was spread on hay stubble. Two porcine enteroviruses were isolated by membrane filtration from 26 samples of surface run-off from land on which pig slurry was routinely spread, and 2 bovine enteroviruses were isolated from cattle feedlot run-off after adsorption to layers of talc and celite followed by hydroextraction. A porcine enterovirus was also isolated from 1 of 33 samples of surface water collected on farms on which pig slurry was routinely spread on the land, but no virus was isolated from 36 samples of ground water from the same farms. The surface water and ground water samples were concentrated by talc-celite adsorption and hydroextraction.",,"['Derbyshire, J. B.', 'Brown, E. G.']",,,,
,PMC,Effects of Ambient Temperatures on Induction of Transmissible Gastroenteritis in Feeder Pigs,,PMC422061,,,"Experiments were carried out to investigate the effects of ambient temperatures on the induction of transmissible gastroenteritis in feeder pigs 2 to 3 months old. Pigs maintained at a high temperature (30 ± 2°C) and exposed to the virulent transmissible gastroenteritis virus did not show clinical signs of the disease during their maintenance at the high temperature. On the other hand, a sudden decrease in the ambient temperature, either before or after virus inoculation, induced severe disease in feeder pigs exposed to the virus. However, continuous maintenance of pigs at the low temperature (4 ± 1°C) tended to somewhat reduce the frequency of occurrence of signs in proportion to the length of the maintenance periods at that temperature. Pigs raised at temperatures that fluctuated between 20 ± 2 and 4 ± 1°C every 24 h developed profuse diarrhea. The duration of clinical signs was longer in pigs maintained under the fluctuating temperatures than in those at the constantly low temperature. With one exception, antibody against transmissible gastroenteritis virus was demonstrated in sera collected from pigs both with and without clinical signs. Antibody titers obtained, however, were somewhat higher in sera collected from pigs that had developed clinical signs than in those from pigs that had endured the infection without showing signs.",,"['Shimizu, Mitsugu', 'Shimizu, Y.', 'Kodama, Y.']",,,,
,PMC,Temperature-sensitive mutants of mouse hepatitis virus produce a high incidence of demyelination.,,PMC392925,,,Mutagenesis of mouse hepatitis virus with 5-azacytidine or 5-fluorouracil yielded several temperature-sensitive mutants. Mutants have been isolated that dramatically enhance the production of demyelinating disease over that previously noted with the wild-type virus. This reproducible model should now make possible the precise elucidation of the pathogenic mechanism and molecular basis of this virus-induced demyelination.,,"['Haspel, M V', 'Lampert, P W', 'Oldstone, M B']",,,,
,PMC,Immune electron microscopy of avian infectious bronchitis virus serotypes.,,PMC275072,,,"An immune electron microscopy agglutination technique in which emphasis is placed upon the importance of antigen-antibody equivalence has been developed as a possible method for the serotyping of avian infectious bronchitis viruses. The Connecticut and Massachusetts 41 serotypes were used as a model system. Stock virus concentrations were standardized by physical particle counts of virions sedimented directly onto electron microscope specimen grids. Suspensions containing approximately 150 virions per grid square were allowed to react with dilutions of homologous and heterologous antisera. Virions in these constant virus-variable serum mixtures were sedimented directly onto electron microscope specimen grids, and the relative degree of aggregation per grid was determined from the mean percent aggregation of five randomly selected grid squares. In homologous assays, regions of relative antibody excess, of equivalence, and of relative antigen excess were clearly evident. At equivalence, the mean percent aggregation was significantly higher than in the regions of relative antibody or antigen excess. In the heterologous systems, the degree of aggregation differed little from that of the virus controls containing no antiserum.",,"['Odenwald, W F', 'Johnson, R B', 'Marquardt, W W', 'Hetrick, F M']",,,,
,PMC,Rotavirus gastroenteritis.,,PMC1544907,,,,,"Walker-Smith, J",,,,
,PMC,RNA of mouse hepatitis virus.,,PMC354060,,,"The RNA of mouse hepatitis virus, a coronavirus, was isolated from the virus released early in the infection and analyzed by sucrose gradient sedimentation and electrophoresis. It was found to consist of a piece of single-stranded RNA of about 60S. Its molecular weight was estimated to be 5.4 X 10(6) by electrophoresis in methylmercury-agarose gels. At least one third of the RNA contained polyadenylated sequences. It is, therefore, probably positive stranded. The virus harvested late in the infection contained, in addition to 60S, some 30 to 50S RNA that are possibly degradation products of the 60S RNA. No difference in the electrophoretic behavior could be detected between the RNA isolated from a pathogenic (JHM) and a nonpathogenic (A59) strain.",,"['Lai, M M', 'Stohlman, S A']",,,,
,PMC,Autoimmune and virus-induced demyelinating diseases. A review.,,PMC2018174,,,"Patterns of demyelination are described in several autoimmune and virus-induced demyelinating diseases of the peripheral and central nervous system. Myelin can be destroyed by injuries that affect either the myelin-supporting cells and/or the myelin lamellae. After destruction of the supporting cells, the related disintegrating sheaths are stripped off axons by invading phagocytes. Virus-induced cytolysis can occur with or without participation of immune responses, as demonstrated in subacute sclerosing panencephalitis and progressive mutlifocal leukoencephalopathy, respectively. Autoimmune demyelination is characterized by disintegration of myelin sheaths in periventular, mononuclear cell infiltrates. Myelin lamellae rather than the myelin-supporting cells are the target of the allergic reaction. The lamellae are lysed in focal areas when in contact with presumably sensitized mononuclear cells. The damaged sheaths are then removed in a nonspecific manner by invading macrophages that strip the myelin remnant off the axons. This sequence of changes is best revealed in experimental and human autoimmune demyelination of peripheral nerves, ie, allergic neuritis and idiopathic polyneutris (the Guillain-Barré syndrome). Autoimmune demyelination triggered by virus infection is described in Marek's disease and postinfectious Theiler's virus myelitis. Changes in canine distemper are discussed with reference to both autoimmune and virus-induced demyelination. The observations are compared with lesions in multiple sclerosis, the most common human demyelinating disease of unknown etiology.",,"Lampert, P. W.",,,,
,PMC,Diagnosis of viral agents associated with neonatal calf diarrhea.,,PMC1277610,,,"During this study, 134 samples have been examined for the detection of the viruses associated with neonatal calf diarrhea. The presence of Nebraska viruses (rotavirus and coronavirus) has been demonstrated by using the electron microscope and the fluorescent antibody techniques while the presence of other viruses has been detected by the observation of a cytopathic effect on monolayer cells of calf testis. The Nebraska viruses have been demonstrated in 107 (80%) out of 134 field case specimens. An association of rotaviruses and coronaviruses was found in 58 cases (54%) whilst the coronaviruses and the rotavirus were found singly in 34 cases (53%) and in 15 cases (14%) respectively. Four bovine virus diarrhea viruses, two infectious bovine rhinotracheitis viruses and two enteroviruses have also been isolated in the preceding 107 Nebraska positive specimens. For the detection of the Nebraska viruses, the fluorescent antibody techniques were more sensitive than the electron microscopy. However, those two techniques must be used simultaneously for a better detection of a greatest possible number of cases.",,"['Marsolais, G', 'Assaf, R', 'Montpetit, C', 'Marois, P']",,,,
,PMC,"Respiratory infection in mice with sialodacryoadenitis virus, a coronavirus of rats.",,PMC421307,,,"Sialodacryoadenitis virus (SDAV), a coronavirus of rats, evoked both serum neutralization and complement fixation antibody responses when inoculated intranasally in mice. Weanling gnotobiotic CD-1 mice inoculated intranasally with 10(3.0) mean tissue culture infective doses of SDAV remained asymptomatic. Virus was recovered from the nasopharynx, trachea, and lung from day 2 to day 7. Viral antigen was readily detected by indirect immunofluorescence in the lung but rarely in the nasopharynx. Infected mice developed interstitial pneumonia. Susceptible mice contact exposed to experimentally infected mice developed antibody to SDAV. Epizootiological studies indicated that retired breeder mice can have complement-fixing antibody to SDAV and mouse hepatitis virus (MHV) in the absence of MHV infection. These studies show that SDAV is infectious for mice and can be a pathogen for the respiratory system. Thus, SDAV infection of mice may be responsible for spurious seroconversions to MHV.",,"['Bhatt, P N', 'Jacoby, R O', 'Jonas, A M']",,,,
,PMC,Human rotavirus enteritis induced in conventional piglets. Intestinal structure and transport.,,PMC372498,,,"To better understand the pathogenesis of infantile viral gastroenteritis, we studied Na+ and Cl- fluxes in vitro in short-circuited jejunal epithelium from 8-10-day-old piglets after infection with a standard dose of human rotavirus given via nasogastric tube. 11 infected piglets, all of whom became ill, were compared with 9 uninfected, healthy litter-mates. When killed 72 h after infection, intestinal villi were shorter and crypts deeper (P less than 0.025) in duodenum, upper jejunum, and mid-small intestine, but not ileum in infected piglets. Virus antigen was seen by fluorescence microscopy in occasional jejunal villus tip cells in only four infected piglets and no controls at 72 h. Net Na+ and Cl- fluxes did not differ from noninfected litter-mate controls under basal conditions, but response to glucose was blunted in infected piglets (P less than 0.001). Theophylline stimulated net Cl- secretion in both infected and control animals, and cyclic AMP concentration in isolated jejunal villus enterocytes did not differ significantly. In isolated jejunal villus enterocytes of infected piglets, thymidine kinase activity increased (P less than 0.001), and sucrase activity decreased (P less than 0.001). We conclude that in this invasive enteritis caused by a major human viral pathogen, glucose-coupled Na+ transport is impaired in the jejunum at a time when the villus epithelium shows enzyme characteristics of crypt epithelium, and when little or no virus is present. These findings are identical to those occurring in an invasive coronavirus enteritis of piglets but differ markedly from those seen with enterotoxigenic diarrhea.",,"['Davidson, G P', 'Gall, D G', 'Petric, M', 'Butler, D G', 'Hamilton, J R']",,,,
,PMC,Polypeptides of the surface projections and the ribonucleoprotein of avian infectious bronchitis virus.,,PMC516003,,,"Purified avian infectious bronchitis virus was digested with bromelain (0.7 mg/ml), and the surface projections were removed. Polyacrylamide gel electrophoresis of the polypeptides from these bromelain-treated particles showed that VP1, VP2, and VP5 were missing from the seven polypeptides. VP1 to VP7, that were present in untreated virus preparations. Milder bromelain treatment (0.07 mg/ml) left visible surface projections and polypeptides comprising VP1 and VP2 intact, but removed VP5. Thus, there are apparently two types of surface projections on the virus particle. The ribonucleoprotein complex was released from virus particles disrupted with 1% Nonidet P-40. The proportion of VP6 in such preparations was greatly reduced, implying that VP6 is the structural polypeptide of the ribonucleoprotein. Polypeptides VP1, VP2, VP4, and VP5 are glycosylated, but none of the polypeptides contains lipid.",,"['Macnaughton, M R', 'Madge, M H', 'Davies, H A', 'Dourmashkin, R R']",,,,
,PMC,Electron microscopy of rapid identification of animal viruses in hematoxylin-eosin sections.,,PMC1277742,,,"Routine hematoxylin-eosin stained, paraffin sections were processed for electron microscopy, using a rapid method for localization of animal viruses. Formalin fixation was effective in preserving DNA as well as RNA viruses, however cellular fine structural details and organelles were not well preserved. The procedure is useful for morphological recognition of viral groups and as a rapid diagnostic aid for identifying viral disease.",,"['Bhatnagar, R', 'Johnson, G R', 'Christian, R G']",,,,
,PMC,Proceedings of the First Vido Symposium on Neonatal Diarrhea,,PMC1277735,,,,,"Derbyshire, J. B.",,,,
,PMC,Transmissible gastroenteritis: demonstration of the virus from field specimens by means of cell culture and pig inoculation.,,PMC1277731,,,"Isolation of transmissible gastroenteritis virus was attempted from segments of jejunum collected from piglets submitted for diagnosis of transmissible gastroenteritis. The virus was isolated more frequently in susceptible piglets than in pig kidney or pig thyroid cells. Practically, both cell systems were equally capable of demonstrating the virus when the tissue suspensions were sonicated. The pig thyroid cells prepared with glands collected from minimal disease pigs were preferred to the pig kidney cells for initial virus isolation because of their ability to respond to transmissible gastroenteritis virus with a progressive cytopathic effect. However, the pig thyroid cells, prepared from pool of glands collected in abattoirs, were often contaminated with parvoviruses and could not be used for diagnostic work. Controlled ultrasound treatments of the inoculum increased the frequency of virus isolation in both cell systems.",,"['Dulac, G C', 'Ruckerbauer, G M', 'Boulanger, P']",,,,
,PMC,Genome of infectious bronchitis virus.,,PMC515914,,,"Techniques are described for the growth and rapid purification of the avian coronavirus infectious bronchitis virus (IBV). Purified IBV has a sedimentation coefficient of 320S and a buoyant density of 1.22 g/ml in sucrose-deuterium oxide equilibrium gradients. IBV RNA extracted by proteinase K in the presence of sodium dodecyl sulfate and further purified by phenol extraction and gradient centrifugation is single stranded and has a sedimentation coefficient of 64S, as determined by isokinetic gradient centrifugation. Analysis on sucrose gradients under both aqueous and denaturing conditions together with agarose gel electrophoresis in the presence of the chaotropic agent methylmercuric hydroxide gave a value of 8 X 10(6) for the moleclar weight of IBV RNA. This value was confirmed by RNase T1 fingerprinting, which also indicated that IBV RNA is haploid. No evidence was found of subunit structure in IBV RNA. From these results together with the recently reported observation that IBV RNA is infectious and contains a tract of polyadenylic acid (Lomniczi, J. Gen. Virol., in press), we conclude that the genome of the coronaviruses is a single continuous chain of about 23,000 mononucleotides that is of messenger polarity.",,"['Lomniczi, B', 'Kennedy, I']",,,,
,PMC,New human adenovirus (candidate adenovirus type 35) causing fatal disseminated infection in a renal transplant recipient.,,PMC274749,,,"An antigenically distinct adenovirus is described which was isolated in March 1973 from the lungs and kidney of a 61-year-old woman who died of diffuse interstitial adenovirus pneumonia 55 days after receiving a cadaveric renal allograft. Complement fixation, hemagglutination inhibition, and serum neutralization tests on sequential serum specimens from the patient confirmed that the adenovirus infection occurred in coincidence with her clinical illness and failed to document concomitant infection by any other common respiratory agent. Pathological and virological findings indicated that the pneumonia was only one manifestation of a disseminated adenovirus infection, the source of which may have been a latent infection pre-existing in the donor kidney. The adenovirus, purified by terminal dilution and plaque procedures, has antigenic, morphological, biological, biophysical, host susceptibility, and hemagglutinating properties characteristic of adenovirus group 1A. Buoyant densities in CsCl are 1.340 g/ml for the virion, 1,300 g/ml for the group complement-fixing (hexon) antigen, and 1.290 g/ml for the major soluble complete hemagglutinin (dodecon). The virus was serologically distinct from adenoviruses 1 to 34 in reciprocal serum neutralization tests with antisera to these viruses. We propose this virus as candidate adenovirus type 35 (holden).",,"['Stalder, H', 'Hierholzer, J C', 'Oxman, M N']",,,,
,PMC,Production by mixed lymphocyte cultures of a type II interferon able to protect macrophages against virus infection.,,PMC421115,,,"In supernatants of mixed mouse spleen cell cultures established for 4 days, a species-specific inhibitor of virus replication with a broad antiviral spectrum was found. The inhibitor was destroyed by trypsin, was nondialyzable and acid labile, and was not neutralized by antibody to mouse L cell interferon. This indicates that in mixed lymphocyte cultures a type II interferon is made that has no immunological relationship with ""fibroblast"" interferon. This leukocyte product was shown to protect mouse hepatitis viruses. It is suggested that lymphocyte interferon may collaborate with macrophages in host defense against viruses, as a mediator of cellular immunity.",,"['Virelizier, J L', 'Allison, A C', 'de Maeyer, E']",,,,
,PMC,Micro-indirect hemagglutination test for detection of antibody against transmissible gastroenteritis virus of pigs.,,PMC274712,,,"A micro-indirect hemagglutination (IHA) test was developed for detecting antibody against transmissible gastroenteritis (TGE) virus of pigs. TGE virus propagated in swine kidney cell cultures was highly purified and concentrated by the combination of ammonium sulfate precipitation, treatment with fluorocarbon, and sucrose density gradient centrifugation. Tanned sheep erythrocytes were sensitized with purified virus for use in the IHA test. The results of testing 104 serum samples collected from pigs in the field indicated that the IHA antibody titers were approximately five times higher than those obtained by a serum neutralization test and that there was good correlation between the antibody titers determined by the two tests. High IHA antibody titers developed in pigs experimentally exposed to virulent TGE virus. Sensitized sheep erythrocytes were stable under long-term storage at 4 degrees C (at least for 50 days). The conclusions made are that the IHA test described is more sensitive than the serum neutralization test for the detection of TGE antibody and may be of value for serodiagnosis of TGE.",,"['Shimizu, M', 'Shimizu, Y']",,,,
,PMC,Solid-Phase Radioimmunoassay for Detecting Bovine (Neonatal Calf Diarrhea) Rotavirus Antibody,,PMC274688,,,"An indirect solid-phase microradioimmunoassay is described for detecting antibodies against rotaviruses. The test involved ethanol fixation of microcultures of bovine rotavirus-infected BSC-1 cells and reaction with bovine antirotavirus serum, followed by (125)I-labeled rabbit anti-bovine immunoglobulin G. The technique was shown to be virus specific and highly sensitive. The fixed microcultures could be stored at 4°C for at least 2 months without affecting the sensitivity of the test. The application of this system for the detection of rotavirus antibodies in humans is briefly discussed.",,"['Babiuk, Lorne A.', 'Acres, Stephen D.', 'Rouse, Barry T.']",,,,
,PMC,Aetiology of acute gastroenteritis in infancy and early childhood in southern India.,,PMC1544698,,,"The aetiology of acute gastroenteritis was studied in 50 infants and young children. Bacterial pathogens were isolated in 33, enteropathogenic E. coli (EPEC), Salmonella, and Shigella being the commonest isolates. Rotaviruses were detected in the stools of 13 of the cases. All children with gastroenteritis in whom rotavirus was detected were seen during the months July to December. In 30 children who served as controls, EPEC were isolated in 6, but rotavirus was detected in none. It is concluded that infection with rotaviruses is a significant cause of morbidity in children with gastroenteritis in southern India.",,"['Maiya, P P', 'Pereira, S M', 'Mathan, M', 'Bhat, P', 'Albert, M J', 'Baker, S J']",,,,
,PMC,Immunoglobulin Classes of Antibodies in Milk of Swine After Intranasal Exposure to Pseudorabies Virus or Transmissible Gastroenteritis Virus,,PMC421058,,,"Experiments were conducted to evaluate whether infection of the respiratory tract of pregnant swine with pseudorabies (Pr) virus would induce the secretion of immunoglobulin A (IgA) antibodies in their milk as was observed after enteric infection with transmissible gastroenteritis (TGE) virus. The immune response of sows to Pr virus inoculated intranasally and to TGE virus inoculated orally/intranasally or via a natural infection was studied. Emphasis was placed upon titers and Ig classes of Pr and TGE virus-neutralizing antibodies in colostrum and milk. All animals exposed to Pr virus (alone or in combination with TGE virus) developed Pr-neutralizing antibody titers in both serum and milk. Pr antibody titers were generally higher in colostrum than in serum, but the opposite was true in milk compared with serum, with milk titers declining markedly during lactation. In contrast, TGE antibody titers in milk from experimentally or naturally infected sows usually remained higher than the corresponding serum titers and persisted at relatively constant levels throughout lactation. Gel filtration studies of milk indicated that the antibody activity against Pr virus was associated almost entirely with IgG fractions, with small amounts of antibody detectable in IgM fractions in colostrum from two of nine sows. By comparison, TGE antibodies were primarily of the IgA class, with varying but lesser amounts of antibody associated with the IgG class. Such results suggest that viral infection of the intestinal tract of the sow, but not the upper respiratory tract, stimulates the secretion of IgA antibodies in the milk.",,"['Saif, Linda J.', 'Bohl, Edward H.']",,,,
,PMC,Quantitation of Antibody to Non-Hemagglutinating Viruses by Single Radial Hemolysis: Serological Test for Human Coronaviruses,,PMC274666,,,"A single radial hemolysis test was developed for quantitation of specific antibody to non-hemagglutinating viruses. With the human coronaviruses as models, this test utilizes the binding properties of the chromic cation to attach viruses to glutaraldehyde-treated sheep erythrocytes. The most satisfactory system consisted of stabilizing washed sheep erythrocytes with 0.0073% glutaraldehyde for 15 min at 23°C, binding a high concentration of virus to a 25% erythrocyte suspension with 0.0016% chromic chloride for 20 min at 23°C, stopping the reaction with phosphate-saline, and finally mixing the treated, rewashed cells with complement and agarose at 45°C to prepare a slide gel. The gel mix, which was dispensed in plastic plates (23 by 73 mm) in 3-ml volumes, consisted of 1% agarose, 0.1% sodium azide, 5% reconstituted complement, and 0.82% treated cells. Wells 2 mm in diameter were loaded with 5 μl of antiserum, incubated for 18 h at 4°C for diffusion of antiserum and fixation of complement, and then incubated for 8 to 24 h at 37°C for development of hemolysis zones. The diameter of a zone was linearly related to antibody concentration, as determined by conventional serological tests. This single radial hemolysis test was applicable to human and animal coronaviruses and to selected serotypes of the adenovirus, picornavirus, rhabdovirus, and rotavirus groups.",,"['Hierholzer, John C.', 'Tannock, Gregory A.']",,,,
,PMC,Mycoplasma-induced hydrocephalus in rats and hamsters.,,PMC421009,,,"Mycoplasma pulmonis, a pathogen of the respiratory tract in rats, was inoculated intracerebrally into neonate rats and hamsters to determine if it would induce lesions in the ependyma. Hydrocephalus was induced in 116 of 120 rats and in 23 of 28 hamsters. The severity of hydrocephalus was greater in the rats than in the hamsters. Hydrocephalus induction occurred only subsequent to inoculation of viable M. pulmonis. At 2 weeks of age, rats became refractory to induction of hydrocephalus. Light microscopy indicated that the hydrocephalus was communicating without an inflammatory response in the ventricles and meninges. Preliminary electron microscopy revealed that amorphous material covered portions of the ependymal surface and that cilia were sometimes matted together. It was suggested that the hydrocephalus was due to ciliary dysfunction or to an imbalance of cerebrospinal fluid secretion and absorption. This M. pulmonis-induced hydrocephalus may be a useful model for elucidating the pathogenesis of certain types of congenital hydrocephalus in humans.",,"['Kohn, D F', 'Kirk, B E', 'Chou, S M']",,,,
,PMC,Use of a free viral immunofluorescence assay to detect human reovirus-like agent in human stools.,,PMC420974,,,Human reovirus-like agent (HRVLA) is a major cause of gastroenteritis in infants and young children in many parts of the world. Detection of HRVLA in stools is impractical with the techniques currently available. We describe a rapid immunofluorescence assay for detection of HRVLA in stools. Results with this assay agreed well with results obtained from examination of stool specimens by electron microscopy.,,"['Yolken, R H', 'Wyatt, R G', 'Kalica, A R', 'Kim, H W', 'Brandt, C D', 'Parrott, R H', 'Kapikian, A Z', 'Chanock, R M']",,,,
,PMC,Recent advances in acute gastroenteritis.,,PMC1879439,,,,,"Larke, R. P.",,,,
,PMC,Field trial evaluation of a reo-coronavirus calf diarrhea vaccine.,,PMC1277709,,,"Field trials were conducted using an experimental, modified live virus, oral vaccine for prevention of reo- and coronavirus calf diarrhea. Prior to the trials, one or both of the specific causative agents were identified from affected calves in each participating herd. In 21 herds, sequential trials were conducted in which results of uninterrupted vaccination were compared with disease rates during a preceding or subsequent control period. In these herds there was a statistically significant reduction in the morbidity and mortality from disease in 1,598 vaccinates compared with the rates in 829 prevaccination control calves. Morbidity and mortality in 206 post-vaccination control calves rose marginally above the rates in the same vaccinates. In 26 other herds, where double blind trials were conducted, rates of morbidity and mortality from disease were virtually the same for 1,080 vaccinated calves and 355 placebo calves. Vaccinates in the sequential trials had the lowest morbidity and mortality rates of any test group in either field trial format. In a selected dairy herd, both field trial formats were implemented and the results compared. In the double blind trial, vaccinates and placebo calves had comparable rates of morbidity and mortality from disease. When a sequential trial was later implemented, a statistically significant reduction in morbidity and mortality occurred in vaccinates compared with rates in control calves.",,"['Thurber, E T', 'Bass, E P', 'Beckenhauer, W H']",,,,
,PMC,Congenital rubella syndrome: continuing challenge of a preventable infection.,,PMC1879339,,,,,"Rhodes, A. J.",,,,
,PMC,New Staphylococcus aureus phage type 94/96(292) associated with a fatal septicemia.,,PMC274599,,,A fulminating septicemia due to Staphylococcus aureus phage type 94/96(292) resulting in the death of a patient with no previous history of illness. This newly characterized strain is identified by an additional typing reaction with experimental phage 292. The prevalence of this strain is discussed.,,"['Ward, E R', 'Blouse, L E', 'Davis, W R', 'Weber, W R']",,,,
,PMC,"Correlation of cytopathic effect, fluorescent-antibody microneutralization, and plaque reduction test results for determining avian infectious bronchitis virus antibodies.",,PMC274597,,,"A microneutralization fluorescent-antibody (MFA) test was effective in determining the level of antibodies to avian infectious bronchitis virus. A comparison of the MFA test with the cytopathic effect microneutralization (MNT) test and 50% plaque reduction (PR) test resulted in positive correlations that were significant (P less than 0.001). The PR test was more sensitive than either the MFA or the MNT test, but there was no significant difference between the sensitivities of the MFA and MNT tests. The MFA test has advantages over the PR test in the capacity to test large numbers of sera in a shorter period of time. The MFA test also can be completed in one-half the time required for the MNT test.",,"['Wooley, R E', 'Brown, J']",,,,
,PMC,Binding effects of concanavalin A on a coronavirus.,,PMC1277703,,,"Concanavalin A, a phytagglutinin, binds to the envelope of hemagglutinating encephalomyelitis virus, a Coronavirus. Concanavalin A treated virus suspensions lose their hemagglutination properties and there is a transient interference with infectivity. Electron micrographs show the Concanavalin A as a granular deposit adhering to the viral envelope and there is aggregation of the virus. Concanavalin A does not bind to virions stripped of their envelopes.",,"['Greig, A S', 'Bouillant, A M']",,,,
,PMC,The role of environmental ammonia in respiratory mycoplasmosis of rats.,,PMC2032551,,,"Young adult, pathogen-free rats of Sherman and Fischer (F344) substrains were inoculated intranasally with 10(8) colony-forming units (GFU) of M. pulmonis and housed for 4 to 6 weeks in environments with ammonia maintained at specific concentrations from 25 to 250 ppm. All levels of NH3--whether produced naturally from soiled bedding or derived from a purified source--significantly increased the severity of the rhinitis, otitis media, tracheitis, and pneumonia (including bronchiectasis) characteristic of murine respiratory mycoplasmosis (MRM). The prevalence of pneumonia, but not that of other respiratory lesions of MRM, showed a strong tendency to increase directly with environmental NH3 concentration. In contrast, NH3 exposure of rats not infected with M. pulmonis caused anatomic lesions that were unlike those of MRM and were limited to the nasal passages. It was concluded that environmental NH3, at concentrations commonly encountered in present day cage environments for rats, plays an important role in pathogenesis of MRM.",,"['Broderson, J. R.', 'Lindsey, J. R.', 'Crawford, J. E.']",,,,
,PMC,Reovirus-like agent associated with fatal diarrhea in neonatal pigs.,,PMC420958,,,"Large numbers of a reovirus-like agent were visualized with electron microscopy in bacteria-free gut homogenates obtained from piglets with a fatal diarrhea resembling transmissible gastroenteritis. The syndrome, of vomiting, diarrhea, dehydration, and death, was reproduced in piglets artificially infected with these bacteria-free gut homogenates. Reovirus-like particles persisted in serial piglet passage and none was seen in uninfected, asymptomatic controls. Hyperimmune sera (made in recovered piglets) aggregated the reovirus-like particles, as judged by immunoelectron microscopy, and neutralized the infectious agent. The cytoplasm in enterocytes on infected intestinal epithelium fluoresced when this hyperimmune sera was used in an indirect fluorescent antibody test. Feeding cow colostrum or diets containing porcine gamma globulin protected infected piglets. No cytopathogenic effect was noted in infected tissue cultures, nor did this agent affect neonatal guinea pigs, hamsters, mice, and rats. The agent did not agglutinate human O or A erythrocytes.",,"['Lecce, J G', 'King, M W', 'Mock, R']",,,,
,PMC,"Morphological and antigenic relationships between viruses (rotaviruses) from acute gastroenteritis of children, calves, piglets, mice, and foals.",,PMC420956,,,"The reovirus-like particles present in the feces of young pigs and foals with acute enteritis and the virus causing epizootic diarrhea of infant mice were found to be indistinguishable morphologically from each other, from the South African SA. 11 and ""O"" viruses, and from the rotaviruses of children and calves. The inner capsid layer of each of these viruses reacted seriologically with sera of children, calves, mice, piglets, and foals convalescent from infection with their respective rotaviruses. These sera reacted by immunofluorescence with human, bovine, porcine, and murine rotaviruses, SA.11, and ""O"" viruses in tissue cultures and with human bovine, procine, nad murine viral antigens by complement fixation and gel diffusion. However, the antisera differed in their ability to react serologically with the outer capsid layer of the viruses investigated and in their ability to neutralize tissue culture-adapted calf virus. These two tests may demonstrate strain or host specificity among rotaviruses. Since the porcine, murine, and equine viruses are closely related serologically to and are morphologically identical to the human and bovine viruses, they should be included in the group of viruses for which the term ""rotavirus"" has been suggested. All known members of this proposed group of viruses share a common antigen, probably situated within the inner capsid layer; thus, any one of the viruses may be used for the preparation of antigen or antibody for diagnostic tests, and this will aid in the diagnosis of virus infection in those species from which a rotavirus has not been cultured.",,"['Woode, G N', 'Bridger, J C', 'Jones, J M', 'Flewett, T H', 'Davies, H A', 'Davis, H A', 'White, G B']",,,,
,PMC,Diagnosis of enteritis virus.,,PMC1864620,,,,,"Flewett, T. H.",,,,
,PMC,Allergy: Viral Infections as Triggers of Asthmatic Attacks,,PMC1237271,,,,,"Terr, Abba I.",,,,
,PMC,Organ culture studies on the efficiency of infection of chicken tissues with avian infectious bronchitis virus.,,PMC2041156,,,"Long-term organ cultures of a range of tissues collected from specific pathogen-free chickens were employed to determine their susceptibility, and their capacity for subsequent virus production, following inoculation with avian infectious bronchitis (AIB) virus. When inoculated with approximately 2-0 log10 median ciliostatic doses (CD50) of a classical highly egg-adapted vaccine strain (H120) of AIB virus, 9 of 23 tissues were shown to be susceptible, namely the nasal turbinates, trachea, air sac membranes,lungsasal turbinates, trachea, air sac membranes, lungs, proventriculus mucosa, thyroid, kidney, ovary and oviduct. When the remaining 14 tissues were inoculated with a high dose of virus (6.8 log10 CD50), the conjunctiva, caecel tonsil, testis and bursa of Fabricius were susceptible whereas the oesophagus and cloaca responded minimally. Inoculation of the same range of tissues with a high or low dose of a field strain (HVI9) of AIB virus produced similar results, except for a number of individual variations in response, due possibly to strain differences in pathogenicity. Determinations of the minimal infectious dose requirements of the susceptible tissues revealed that the efficiency of infection with the H120 strain was highest for the nasal turbinate and tracheal tissues, and thereafter, in order of decreasing efficiency, were the air sac membranes, lung, oviduct, proventriculus mucosa, conjunctiva, kidney, ovary, bursa of Fabricius, thyroid, testis, caecal tonsil, cloaca and oesophagus. The relevance of these results is discussed in connection with the early events in the pathogenesis and the clinical syndrome of AIB infection in chickens.",,"['Darbyshire, J. H.', 'Cook, J. K.', 'Peters, R. W.']",,,,
,PMC,The efficacy of a modified live reo-like virus vaccine and an E. coli bacterin for prevention of acute undifferentiated neonatal diarrhea of beef calves.,,PMC1697302,,,,,"['Acres, S D', 'Radostits, O M']",,,,
,PMC,Diarrhea in gnotobiotic calves caused by the reovirus-like agent of human infantile gastroenteritis.,,PMC420908,,,"Gnotobiotic newborn calves were found to be susceptible to infection with the reovirus-like agent of human infantile gastroenteritis (HRVL). Infection was based on (i) seroresponse using immunofluorescence and (ii) fecal shedding of virus particles using electron microscopy. Virus was detected in fecal samples for at least 2 to as long as 7 days after inoculation, although peak virus concentrations were observed on days 1 to 4. Diarrheal illness was observed in seven calves on second to fourth serial passage of HRVL in calves but in none of four animals studied on first passage. Diarrhea began 15 to 30.5 h (mean = 22.3 h) post-inoculation and lasted less than 24 h; three of the seven animals that developed diarrhea were also depressed or anorectic.",,"['Mebus, C A', 'Wyatt, R G', 'Sharpee, R L', 'Sereno, M M', 'Kalica, A R', 'Kapikian, A Z', 'Twiehaus, M J']",,,,
,PMC,Pathological and microbiological observations made on spontaneous cases of acute neonatal calf diarrhea.,,PMC1277758,,,"The purpose of this report is to describe clinical signs, gross and microscopic lesions, bacteriological and immunofluorescence observations made on spontaneous cases of acute neonatal calf diarrhea (NCD) in dairy and beef herds. The following diagnostic tools were used: 1) direct smears of intestinal content, 2) Escherichia coli counts, 3) aerobic bacterial cultures of the small intestine and other organs (The O serogroup and the enterotoxigenicity of the E. coli isolated was determined), 4) detection of the two Nebraska NCD viruses (reo-like and corona-like) by the fluorescent antibody technique and 5) histological examination on different segments of the digestive tract. The following etiological diagnoses were suggested after post mortem examination of 55 cases of NDC (34 were submitted alive): reo-like virus only (1), reo-like virus + E. coli (4), reo-like virus + cryptosporidium (2), reo- + corona-like viruses (5), reo- + corona-like viruses + cryptosporidium (3), reo- + corona-like viruses + infectious bovine rhinotracheitis virus (1), coronavirus-like agent only (2), coronavirus-like agent + mycotic abomasitis (1), coronavirus-like agent + crytosporidium (1), E. coli only (6), cryptosporidium only (5), mycotic abomasitis (3), mycotic rumenitis + reticulitis (1) and undetermined (20). Most of the calves in the last group were submitted dead.",,"['Morin, M', 'Larivière, S', 'Lallier, R']",,,,
,PMC,In vitro differentiation and pH sensitivity of field and cell culture-attentuated strains of transmissible gastroenteritis virus.,,PMC420814,,,"Characteristics of four transmissible gastroenteritis (TGE) virus field strains (Miller, Purdue, Bl, and V203) and four cell culture-attenuated strains (Purdue, SH, CKp, and Bl) were studied to find methods of differentiation between the two groups of viruses. TGE field virus strains did not replicate as well as attenuated strains at 37 C and could not be passaged serially for more than four to six passages at 33 C. There were clear differences in plaque size when the strains were compared. Field strains had average plaque sizes ranging from 3.59 to 3.15 mm, whereas attenuated strains induced plaques that were larger than 4.2 mm. Variations were observed in stability of strains at pH 3.0. Field strains and cell culture-attenuated strains CKp-270 and SH-114 were reduced in titer by about 1 log10. A reduction of about 3 log10, however, was obtained with cell culture strains B1-300 and Purdue-113.",,"['Hess, R G', 'Bachmann, P A']",,,,
,PMC,Studies of experimental rhinovirus type 2 infections in polar isolation and in England.,,PMC2129668,,,"After five months of total isolation a wintering party of seventeen British Antarctic Survey (BAS) personnel was inoculated under double blind concitions with placebo, or rhinovirus type 2 which had been propagated in tissue culture. The clinical and virological responses of these subjects were compared with those of volunteers in England who received a similar dose of the same strain. The virus used was apparently partly attenuated for man; at the dosage used its effects in England were similar to a smaller dose of an unattenuated strain, but in the Antarctic it caused relatively severe infections. Both the symptoms and the laboratory evidence of virus infection appeared to be more pronounced in the BAS subjects than in the volunteers in England who received the same challenge. In the former group the infection readily spread to those who were originally given placebo. In the BAS subjects serum antibody titres were well maintained during the isolation period but a significant fall in nasal immunoglobulin concentration was recorded during the 5 months of isolation after the virus challenge. Possible mechanisms for the increased sensitivity to rhinovirus of subjects who have been totally isolated in a small closed community are discussed.",,"['Holmes, M. J.', 'Reed, S. E.', 'Stott, E. J.', 'Tyrrell, D. A.']",,,,
,PMC,Use of the hemadsorption phenomenon for determining virus and neutralizing antibody titers of rabies.,,PMC420780,,,"Chicken embryo cells infected with the HEP Flury strain of rabies virus adapted to tissue culture produced a hemadsorption (HAD) phenomenon by using goose erthyrocytes. The optimal conditions for HAD included the incubation of cell cultures at 37C for 3 days after virus inoculation, the use of a 0.4% suspension of goose erythrocytes in phosphate buffer adjusted at pH 6.2, and adsorption of erythrocytes at 4C. This phenomenon was inhibited with anti-rabies serum. Virus titer obtained with the HAD technique was almost the same as with the fluorescent antibody technique or the intracerebral inoculation of suckling mice. Results of the neutralization test by using the HAD technique could be easily determined 3 days after inoculation of chicken embryo cells with the mixture of 100 mean tissue culture infective doses of virus and diluted serum. The neutralizing antibody titers coincided with those obtained in mice.",,"['Minamoto, N', 'Kurata, K', 'Kaizuka, I', 'Sazawa, H']",,,,
,PMC,Antibody response in pigs inoculated with transmissible gastroenteritis virus and cross reactions among ten isolates.,,PMC1277551,,,"Groups of two or three day old pigs were inoculated intravenously with cell culture grown transmissible gastroenteritis virus. A single or a multiple dosage schedule was used. The magnitude of immune response was measured in terms of serum neutralization indices. A single dose of relatively attenuated virus caused mild clinical signs of transmissible gastroenteritis infection in the pigs and induced a low level of antibody in the serum by the seventh day after inoculation. Repeated injections of virus at seven day intervals stimulated little increase in antibody titers. However, high serum antibody titers were obtained for all pigs if the time interval between injections was extended to 15 days. Sera obtained early after exposure to live transmissible gastroenteritis virus contained mainly IgM antibody whereas sera obtained later after exposure contained mainly IgG antibody. Ten plaque purified isolates of transmissible gastroenteritis virus, comprising eight American isolates, one Japanese isolate and one British isolate were indistinguishable by means of reciprocal plaque reduction neutralization tests.",,"Kemeny, L J",,,,
,PMC,Transmissible gastroenteritis virus: plaques and a plaque neutralization test.,,PMC1277545,,,"A plaquing system and plaque neutralization test in porcine thyroid cells were used to study different transmissible gastroenteritis isolates and hemagglutinating encephalomyelitis virus. Among transmissible gastroenteritis virus isolates, plaque size varied considerably and mixed size ranges sometimes occurred. The most recently isolated viruses produced smaller plaques than the laboratory viruses or hemagglutinating encephalomyelitis virus. All transmissible gastroenteritis virus isolates reacted in the plaque neutralization test with a transmissible gastroenteritis virus antiserum which showed no activity against hemagglutinating encephalomyelitis virus. Plaque neutralization results both from experimentally infected pigs and following a field outbreak demonstrated the reliability of this test and its greater sensitivity than the conventional tube test.",,"['Thomas, F C', 'Dulac, G C']",,,,
,PMC,The detection of transmissible gastroenteritis viral antibodies by immunodiffusion.,,PMC1277542,,,"Precipitating antibodies against transmissible gastroenteritis viral antigens were detected by the immunodiffusion test in two transmissible gastroenteritis viral hyperimmune antisera and in antiserum prepared against haemagglutinating encephalomyelitis virus but not in sera from several species of normal animals, in antisera prepared against a variety of othet viruses and bacteria or sera from swine with bacterial enteritis. When the immunodiffusion test was compared with the virus neutralization test for the detection of transmissible gastroeneritis viral antibodies in 20 swine sera certain samples which contained high titres of virus neutralizing antibodies failed to produce precipitation while other sera were positive in the immunodiffusion test although their virus neutralizing antibody titres were relatively low. Precipitating antibodies were also detected by immunodiffusion in several samples of milk whey from a sow which had been vaccinated with inactivated transmissible gastroenteritis virus.",,"['Bohac, J', 'Derbyshire, J B']",,,,
,PMC,Effect of ambient temperatures on multiplication of attenuated transmissible gastroenteritis virus in the bodies of newborn piglets.,,PMC420704,,,"Newborn piglets were found to be more resistant to infection with attenuated transmissible gastroenteritis virus when maintained at higher temperatures. This was attributed to a decreased rate of virus propagation and spreading in the bodies of the infected animals. The highest virus levels were detected in the tissues of piglets maintained at 8 to 12 C. In contrast, no virus was recovered from piglets maintained at 35 to 37.5 C. The virus was found only in the lymph nodes and respiratory organs in the piglets maintained at 20 to 23 C.",,"['Furuuchi, S', 'Shimizu, Y']",,,,
,PMC,"Detection of neonatal calf diarrhea virus, infant reovirus-like diarrhea virus, and a coronavirus using the fluorescent virus precipitin test.",,PMC274302,,,"Thirty-four calf and five infant fecal specimens were tested for the neonatal calf diarrhea virus (NCDV) and for the reovirus-like infantile diarrhea agent; respectively. The procedures used were the fluorescent virus precipitin test and immune electron microscopy. Fourteen of the calf stools contained detectable NCDV, and four of the five infant stools contained the reovirus-like human agent. Infectious NCDV was detected in four of the 34 calf fecal specimens when Madin-Darby bovine kidney cell cultures that had been inoculated with supernatant fluids from stool suspensions were stained with fluorescent antibody. The 20 calf stools that did not have detectable virus were examined for the bovine corona diarrhea virus. Coronavirus was found in two of these specimens.",,"['Peterson, M W', 'Spendlove, R S', 'Smart, R A']",,,,
,PMC,Transient acute myositis in childhood.,,PMC1545896,,,Eight cases of transient acute polymyalgia with weakness are described. All had abnormal serum creatine phosphokinase levels and most had minor haematological abnormalities at the time of diagnosis. Virological studies were performed with negative findings.,,"['McKinlay, I A', 'Mitchell, I']",,,,
,PMC,Partial characterization of the principal soluble antigens associated with the coronavirus of transmissible gastroenteritis by complement fixation and immunodiffusion.,,PMC420642,,,"A microtiter complement fixation (CF) test to detect transmissible gastroenteritis (TGE) viral antigen was developed, using TGE hyperimmune pig serum as an antibody source. Sera from TGE covalescent pigs did not fix complement by this test. Maximal virus and soluble antigen (SA) titers were obtained 36 to 48 h after inoculation of swine testes cells. Cell-associated virus and SA titers were higher than those in the culture fluid, which had to be concentrated 20X before use as antigen in agar immunodiffusion tests (ID). By sucrose density-gradient centrifugation, the SA had a buoyant density of 1.10 g/ml and could be separated from the virus that banded in the 1.19-g/ml region. Virus and SA from three different isolates of TGE had the same buoyant densities. Heating and proteolytic enzyme digestion established the protein nature of the SA. As assayed by CF and ID, there were stability differences between crude and purified preparations of SA. Antibody prepared in rabbits against the SA neutralized the TGE virus.",,"['Stone, S S', 'Kemeny, L J', 'Jensen, M T']",,,,
,PMC,Comparison of a microneutralization test in cell culture and virus neutralization test in embryonated eggs for determining infectious bronchitis virus antibodies.,,PMC274251,,,"A microneutralization test (MNT) system utilizing cytopathic effect end points was effective in determing neutralization indexes for infectious bronchitis virus antibodies. The system is reproducible within 1 index unit at the 95% level of probability. Comparison of the MNT to tests in eggs resulted in a positive correlation (B =0.81), which was significant (P greater than 0.01). The quantitative dose-response relationship of the MNT is linear (P greater than 0.005), with the 95% prediction limits fitting between one 10-fold dilution.",,"['Wooley, R E', 'Brown, J', 'Davis, R B', 'Blue, J L', 'Lukert, P D']",,,,
,PMC,"Influenza and other acute respiratory diseases in the Czech Socialist Republic, 1969-1974",,PMC2366590,,,"Since 1969, the incidence of acute respiratory diseases (ARD) in the Czech Socialist Republic of Czechoslovakia has been monitored by a special programme based on reports from 85 district epidemiological centres. In this paper, the incidence of ARD in three age groups, together with the incidence of complications and death rates, are presented for each season during the period 1969-1974. The significance of epidemiological observations and laboratory investigations relating to influenza and other ARD agents, such as parainfluenza viruses, adenoviruses, rhinoviruses, RS virus, coronaviruses, and Mycoplasma pneumoniae, is discussed.",,"['Strnad, P.', 'Tŭmová, B.', 'Syrŭček, L.', 'Fedová, D.', 'Brůčková, M.', 'Kunzová, L.', 'Štumpa, A.', 'Střížová, V.', 'Berkovičová, V.', 'Losová, M.']",,,,
,PMC,A prospective study of acute viral hepatitis with particular reference to hepatitis A,,PMC2366443,,,"In order to investigate the relationship of hepatitis A antigen to viral hepatitis, a prospective study was carried out on 97 patients admitted to Fairfield Hospital, Melbourne, with suspected viral hepatitis, and 3 of their family contacts. Evidence of infection with hepatitis A virus was obtained by detecting hepatitis A antigen in stools, and/or antibody to it in sera, by immune electron microscopy. Infection with hepatitis B virus was determined by testing for hepatitis B surface antigen and antibody in serum, by solid phase radioimmunoassay. Sixteen patients were found to have diseases other than viral hepatitis and 2 patients (child contacts) suffered no illness. There was clinical and/or biochemical evidence compatible with viral hepatitis in 82 patients, of whom 35 were confirmed as having hepatitis A and 31 as having hepatitis B infections. In the remaining 16 patients there was no evidence of infection with either hepatitis A or B virus. It is possible that some of these patients may have been infected with viral agents as yet unidentified.",,"['Locarnini, S. A.', 'Gust, I. D.', 'Ferris, A. A.', 'Stott, A. C.', 'Wong, M. L.']",,,,
,PMC,Travelers' Diarrhea and Others,,PMC1130438,,,,,"Greenberg, Richard N.",,,,
,PMC,Neuropathological effects of persistent infection of mice by mouse hepatitis virus.,,PMC415408,,,"Mouse hepatitis virus (MHV3) can persist for months in strains of mice with genetically controlled ""semisusceptibility"" to this virus. The pathology of the chronic neurological disease induced in these animals has been investigated by conventional histology and immunofluorescence. A2G mice develop a chronic choroidoependymitis and meningitis leading to severe hydrocephalus and hydromyelia. In C3H mice a widespread vasculitis was observed, with both viral antigens and bound immunoglobulins in vessal walls. No significant glomerulonephritis was found. Systemic amyloidosis was present in the spleen, liver, and kidneys. The virus was not detected in neural tissues, but brain and spinal cord lesions were found near inflammatory areas surrounding damaged vessels. It is suggested that viral persistance in ependymal cells is directly responsible for the lesions in A2G mice, whereas an immunopathological lesion of blood vessels of the central nervous system underlines the damage to mice of the C3H strain.",,"['Virelizier, J L', 'Dayan, A D', 'Allison, A C']",,,,
,PMC,Transmissible gastroenteritis (TGE) of swine: effect of age of swine testes cells culture monolayers on plaque assays of TGE virus.,,PMC1277500,,,"A continuous line of swine testes cell culture monolayers was infected at various ages with both cell culture-adapted transmissible gastroenteritis (TGE) virus and tissue infected with TGE virus. Both produced increasing numbers of plaques as the cell monolayers aged from two to five days. Therefore, allowing the swine testes cell monolayer to age five to six days before inoculation should increase the likelihood of detecting TGE virus by plaque assay.",,"['Stark, S L', 'Fernelius, A L', 'Booth, G D', 'Lambert, G']",,,,
,PMC,Viral susceptibility of a cell line derived from the pig oviduct.,,PMC1277495,,,"Seventeen of 24 RNA viruses and eight of nine DNA viruses replicated in a cell line derived from a pig fallopian tube. The following RNA viruses grew poorly in it: the virus of transmissible gastroenteritis of pig and the swine-influenza, Sendai and bovine para-influenza type 3 viruses. Among other RNA viruses an untyped swine para-myxovirus and some picornaviruses, rhabdoviruses and togaviruses attained high titers and produced an extensive cytopathic effect. Among the DNA viruses a porcine adeno, equine rhinopneumonitis, infectious bovine rhinotraceheitis, pseudorabies and porcine cytomegalo viruses replicated in pig fallopian tube cells as well as in other cells generally used to grow them.",,"['Bouillant, A M', 'Dulac, G C', 'Willis, N', 'Girard, A', 'Greig, A S', 'Boulanger, P']",,,,
,PMC,Infectious diseases: fortieth and final annual review of significant publications.,,PMC2496191,,,,,"Reimann, H. A.",,,,
,PMC,"Observations on abortions in cattle: a comparison of pathological, microbiological and immunological findings in aborted foetuses and foetuses collected at abattoirs.",,PMC1277458,,,"Fifty nonaborted and 50 aborted bovine foetuses were examined utilizing histology, immunoelectrophoresis, bacteriology and the fluorescent antibody technique. Lesions were observed in 12 of the nonaborted foesuses and in four of these immunoglobulins were demonstrated. In addition, two of the nonaborted foetuses had immunoglobulins in the absence of observed lesions. Lesions were observed in 48 of the aborted foetuses and immunoglobulins were detected in 22 of these. An etiological diagnosis was arrived at in 24 of the 50 aborted foetuses. The tissues most frequently observed to have lesions of diagnostic significance were eyelid, intestine, liver, lung and placenta. Intestinal lesions were observed in several foetuses in association with a variety of agents including infectious bovine rhinotracheitis. Foetuses diagnosed as aborting because of mycotic infection consistently displayed lesions in their eyelids. The value of taking eyelid sections in cases of suspected mycotic abortions, the significance of foetal intestinal lesions, the evaluation of abomasal aspirates and the diagnostic importance of immunoglobulin determinations in aborted foetuses are discussed.",,"['Miller, R B', 'Quinn, P J']",,,,
,PMC,Failure of attenuated temperature-sensitive influenza A (H3N2) virus to induce heterologous interference in humans to parainfluenza type 1 virus.,,PMC415245,,,"The present investigation was undertaken to determine if a candidate live vaccine virus, influenza A/Hong Kong/68-ts-1 [E] (H3N2), induced heterologous interference against an interferon-sensitive, wild-type, parainfluenza type 1 challenge virus. The parainfluenza virus was administered 7 days after Hong Kong/68-ts-1 [E] virus infection. The clinical response, daily quantitative virus shedding, interferon production, and serum and nasal wash antibody responses were determined in an experimental group (influenza A virus followed by parainfluenza virus) and 10 volunteers in a control group (parainfluenza virus only). The volunteers were selected on the basis of susceptibility to the two viruses, i.e. serum hemagglutination-inhibition antibody titer of is less than or greater to 1:8 for influenza virus and low nasal wash antibody titer (is less than or greater to 1:8) for parainfluenza virus. Despite a 100% infection rate in the Hong Kong/68-ts-1 [E] vaccinees, no heterologous interference was induced against the parainfluenza type 1 virus challenge.",,"['Murphy, B R', 'Richman, D D', 'Chalhub, E G', 'Uhlendorf, C P', 'Baron, S', 'Chanock, R M']",,,,
,PMC,In vivo microscopic observations of the pathogenesis of acute mouse viral hepatitis.,,PMC2072702,,,"In vivo microscopy of the liver was undertaken to determine the extent of involvement of the hepatic microvascular system in mice infected with viral hepatitis (MHV-3). It was found that the major effects of the disease were produced in localized areas where parenchyma, sinusoids and blood were obliterated. However, immediately peripheral to these lesions blood flow and vessels were unaffected other than by localized hypertrophy of Küpffer cells. While each lesion produced a sinusoidal block to blood flow, portal hypertension did not occur even in the presence of extensive focal and confluent necrosis.",,"['Bloch, E. H.', 'Warren, K. S.', 'Rosenthal, M. S.']",,,,
,PMC,New human adenovirus isolated from a renal transplant recipient: description and characterization of candiate adenovirus type 34.,,PMC275094,,,"An antigenically distinct adenovirus is described which was isolated in March 1972 from the urine of a 17-year-old Caucasian male who was experiencing fever after receiving a kidney transplant from a cadaver in February. The adenovirus could not be isolated in April from a pharyngeal swab which yielded cytomegalovirus. Complement-fixation, hemagglutination-inhibition, and/or serum-neutralization tests on sequential serum specimens from the patient confirmed that the adenovirus infection occurred during March and showed that infections with cytomegalovirus and respiratory syncytial virus also occurred during late March and April. The patient's persistent fever, for which other causes could not be found, may have been associated with one or more of these infections. Upper respiratory symptoms and lung involvement were not found during this period. Mild liver dysfunction during this time could not be clearly related to adenovirus infection because of the presence of multiple other causes. The adenovirus may have been latent in the donor kidney and become active in the new host as a consequence of immunological impairment. The adenovirus, purified by terminal dilution and plaque procedures, has antigenic, morphological, biophysical, host susceptibility, and hemagglutinating properties characteristic of adenovirus group IA. Buoyant densities in CsCl are 1.340 g/ml for the virion, 1.304 g/ml for the group CF antigen (hexon), 1.295 g/ml for the major soluble complete hemagglutinin (dodecon), and 1.206 g/ml for the minor soluble complete hemagglutinin (tentatively, fiber dimer). The virus does not cross-react in reciprocal hemagglutination-inhibition and serum-neutralization tests with antisera to adenovirus types 1 to 33. We propose this virus as candidate adenovirus type 34 (Compton).",,"['Hierholzer, J C', 'Atuk, N O', 'Gwaltney, J M']",,,,
,PMC,Isolement du virus de la gastro-entérite transmissible du porc sur cultures cellulaires et comparaisons antigéniques avec deux souches américaines,,PMC1696831,,,,,"['Dulac, G C', 'Boulanger, P', 'Phaneuf, J B']",,,,
,PMC,Use of electron microscopy for detection of viral and other microbial contaminants in bovine sera.,,PMC275026,,,"A total of 25 lots of bovine serum samples were pelleted in Beem capsules for thin sectioning and were examined by electron microscopy. These included 17 lots of fetal bovine serum pools and five lots of calf serum pools obtained from commercial sources, and three lots of adult bovine serum from local dairy farms. Virus-like particles, 50 to 300 nm in diameter, were detected in 17 of 25 (68%) of the sera. Five of 25 serum samples showed the presence of mycoplasma-like agents. Incubation of bovine serum at 35 C for 1 or 2 weeks appeared to destroy some of these agents, but in certain instances it enhanced bacteria and bacteriophage contaminants. The advantages of electron microscopy using the thin-sectioning technique for detection of microbial contamination in bovine sera are illustrated.",,"['Fong, C K', 'Gross, P A', 'Hsiung, G D', 'Swack, N S']",,,,
,PMC,pH Stability Studies with Avian Infectious Bronchitis Virus (Coronavirus) Strains,,PMC354472,,,"A comparison of 17 infectious bronchitis virus strains, using the same test procedure and assay system, demonstrated that stability at an acid pH is a variable characteristic of the avian coronaviruses.",,"['Cowen, B. S.', 'Hitchner, S. B.']",,,,
,PMC,Lassa virus infection in Mastomys natalensis in Sierra Leone: Gross and microscopic findings in infected and uninfected animals,,PMC2366654,,,"Pathological examinations of 28 wild-caught Mastomys natalensis from Sierra Leone, 14 of which were positive for Lassa virus by tissue culture, are reported. The high frequency of neoplastic and degenerative diseases observed among older animals in closed colonies of M. natalensis were not observed in the wild animals studied. This is probably a reflection of the age distribution of the study population, since the life expectancy of wild Mastomys is less than a year. Inflammatory lesions were nonetheless identified, some of which were similar to those described in laboratory colonies. Frequent lesions were myocarditis (54%), myositis (32%), interstitial pneumonitis (50%), intercapillary glomerulosclerosis (36%), and acute nephrosis (14%). Follicular and nodular lymphoid hyperplasia were evident in the spleen (74%) and Peyer's patches (64%). Lymphoid cell accumulations were prominent in the salivary glands (36%), periportal hepatic region (25%), lungs (32%), perivascular regions (36%), and kidney (21%). Cytomegalic inclusion body sialoadenitis was common (25%). Coccidiosis was evident in the intestinal tract (25%), kidney (25%), and muscle (21%). One neoplasm, a parahepatic haemangioma, was observed histologically. Mean body weights and lengths for virus-positive animals (33 g and 9.2 cm) and virus-negative animals (54 g and 12.2 cm) showed that virus-positive animals were smaller in weight and shorter in length. Since the age of the animals could not be determined, these differences remain unexplained. In comparison with virus-negative animals, virus-positive Mastomys had higher frequencies of splenic follicular hyperplasia (82% against 50%), myocarditis (79% against 29%), perivascular lymphoid cell accumulation (57% against 7%), myositis (50% against 14%), and cytomegalic inclusion body sialoadenitis (36% against 14%). The frequency of lymphoid hyperplasia of Peyer's patches was high in both groups of animals (71% and 57%). The presence of Lassa virus, small size, myocarditis, and lymphoid perivasculitis appeared to be interrelated, but larger and better controlled studies are required to elucidate the relationship.",,"['Demartini, J. C.', 'Green, D. E.', 'Monath, T. P.']",,,,
,PMC,The detection of transmissible gastroenteritis viral antigens by immunodiffusion.,,PMC1277416,,,"Parathyroid (PT) glands from 20-day-old embryonic chicks cultured in a chemically defined medium secreted a stimulator of in vitro bone resorption. This stimulator was presumed to be parathyroid hormone (PTH) because: 1) the in vitro dose response curve was parallel to that obtained with bovine PTH; 2) the activity was eluted on Sephadex G-1--chromatography at a postition similar to that for PTH; and 3) the material produced hypercalcemia in vivo in chicks. The amount of PTH-activity secreted was inversely proportional to the calcium concentration of the medium over the range of 0.75-2.25 mM. The chick PT glands also secreted an inhibitor of PTH-stimulated bone resorption in vitro. This inhibitor was presumed to be calcitonin (CT) because: 1) the in vitro dose-response curve was parallel to that obtained with synthetic salmon CT; 2) the activity was eluted on Sephadex G-50 chromatography at a position similar to that for salmon CT; and 3) the material produced hypocalcemia in vivo in rats. In contrast to what would be expected for CT secretion, the CT-activity was secreted by the PT glands in response to a low, not high calcium concentration. The data suggest that the secretion of avian PTH is similar to that of the mammalian hormone, and that the ultimobranchialectomized chick with an intact parathyroid gland may not be deficient in CT.",,"['Bohac, J', 'Derbyshire, J B', 'Thorsen, J']",,,,
,PMC,A new look at infectious gastroenteritis.,,PMC1129644,,,,,"St Geme, J W",,,,
,PMC,Maladies porcines à étiologie virale dans la province de Québec. III. Encéphalomyélite et infection à virus para-influenza,,PMC1696708,,,,,"['Gagnon, A N', 'Greig, A S', 'Marsolais, G', 'Lussier, G', 'Marois, P']",,,,
,PMC,Differentiation of Four Adenovirus Types by Macrophage Migration Inhibition Tests,,PMC422978,,,"The macrophage migration inhibition (MMI) test was found to be a satisfactory procedure for distinguishing between adenovirus types 1, 4, 5, and 7. Highly purified virus preparations were used for the sensitization of Hartley strain guinea pigs, whereas the MMI test antigen consisted of crude virus preparations grown in KB cells. With all four virus types, a significantly greater MMI response was noted when peritoneal exudate cells were exposed to the homologous sensitizing antigen as compared to that obtained with the three heterologous antigens. Studies with adenovirus type 1 indicate that sensitizing doses between 70 and 150 μg of viral protein per guinea pig gave the optimal MMI response. Doses below 70 μg did not stimulate the delayed response, whereas doses above 120 μg produced MMI reactions which were nonspecific, as differences between homologous and heterologous antigens were not demonstrable.",,"['Novotny, James F.', 'Hetrick, Frank M.', 'Via, David']",,,,
,PMC,A Case of Viral Neonatal Calf Diarrhea in a Québec Dairy Herd,,PMC1319861,,,"This report is concerned with a consistent problem of neonatal calf diarrhea (NCD) in a dairy herd in which, for nearly two years, the morbidity had approached 100% and the mortality had varied from 20% to 45%. Generally, diarrhea appeared at three days of age. By the fluorescent antibody tissue section technique the two Nebraska NCD viruses (reo-like and corona-like) were detected in the cytoplasm of many absorptive cells of the small intestine from a calf submitted for necropsy. Reo-like virus antigen was not detected in the absorptive and crypt cells of the colon but coronavirus-like antigen was. An adenovirus was also isolated from the small intestine of this calf. The disease was reproduced experimentally in a two day old colostrum deprived calf with a bacteria free intestinal homogenate obtained from the naturally infected calf. Both Nebraska NCD viruses were demonstrated in this experimental animal. However, the adenovirus was not re-isolated. Histological lesions observed in the small and large intestines of the naturally and experimentally infected calves were similar and because of their good correlation with the immunofluorescent findings, a combination of the two Nebraska NCD viruses was thought to be a major cause of the neonatal calf diarrhea problem afflicting this dairy herd.",,"['Morin, M.', 'Lamothe, P.', 'Gagnon, A.', 'Malo, R.']",,,,
,PMC,Viral infections of the liver in childhood,,PMC2495728,,,"Hepatitis A and hepatitis B viruses and yellow fever virus are the most important causes of acute inflammation of the liver. Hepatitis is also frequently associated with other common viral infections such as cytomegalovirus (human herpesvirus 5) and EB virus (human herpesvirus 4). In addition, there are a number of viruses which occasionally display increased hepatotropism producing a clinical picture which is similar to classical hepatitis.",,"Zuckerman, A. J.",,,,
,PMC,Transmissible Gastroenteritis MECHANISMS RESPONSIBLE FOR DIARRHEA IN AN ACUTE VIRAL ENTERITIS IN PIGLETS,,PMC302621,,,"We studied 3-wk-old piglets 40 h after experimental infection with transmissible gastroenteritis (TGE) virus to identify the mechanisms of diarrhea in this disease and to better understand infectious diarrhea in humans. Using continuous segmental marker perfusion in four regions along the gut, we found significant increases in net intraluminal accumulation of water and electrolytes only in the proximal jejunum, the region infected by the virus. In this jejunal segment studied in vivo, unidirectional sodium flux, extracellular fluid (ECF) to lumen, significantly increased, lumen to ECF significantly decreased, compared with matchfed littermates. The standard perfusate rendered hypertonic by adding mannitol (450 mosmol/kg), in the same segment of normal pigs, caused only an increase in ECF to lumen flux of sodium. TGE did not alter gross villous structure or intraluminal bacteria, bile salts, lactate, pH, or osmolality. Epithelial cell migration was accelerated in the jejunum of infected pigs. Isolated in suspension, these cells from TGE pigs exhibited increased active and passive sodium efflux, cells from mannitol-perfused pigs exhibited only increased active sodium efflux. In this viral enteritis, altered sodium transport occurring in the jejunum, the region of the intestine infected appears to be associated with defective epithelial cell function. The precise nature of the abnormalities in sodium transport, their relationship to disturbances of transport of other solutes, and to virus epithelial cell interaction remain to be defined.",,"['Butler, D. G.', 'Gali, D. G.', 'Kelly, M. H.', 'Hamilton, J. R.']",,,,
,PMC,"Virus isolations from patients in general practice, 1961-71",,PMC2130502,,,"During the period 1961-71 of 1785 viruses isolated from patients in the general population 503 (28%) were rhinoviruses, 465 (26%) influenza viruses, 248 (14%) enteroviruses, 234 (13%) herpes simplex virus, 132 (7%) parainfluenza viruses, 129 (7%) adenoviruses and 49 (3%) respiratory syncytial virus. Also isolated were 18 strains of mumps virus, 7 coronaviruses and 295 streptococci of groups A, C or G. Fluctuations were observed in the frequency with which respiratory syncytial virus, parainfluenza virus type 2, and the adenoviruses were isolated over the 10-year period. Influenza viruses types A and B, parainfluenza viruses types 1 and 2, respiratory syncytial virus, adenoviruses types 3, 4, 6, 7 and 21, and many enteroviruses were all associated with outbreaks. Infections with influenza viruses A and B and parainfluenza viruses types 1 and 2 came during the winter, whereas those with parainfluenza virus type 3, enteroviruses, and rhinoviruses were more frequently seen in the summer and early autumn.",,"Higgins, P. G.",,,,
,PMC,A seven-year study of WHO virus laboratory reports on respiratory viruses,,PMC2366317,,,"In 1963 the World Health Organization established a system for the collection and distribution of information on viruses. By 1973 laboratories in 45 countries were participating in this scheme. The present study is an analysis of the reports on adenovirus, influenza viruses A, B, and C, parainfluenza virus, respiratory syncytial (RS) virus, rhinovirus, and Mycoplasma pneumoniae during 1967-73. In the northern hemisphere, from which over 95% of the reports were received, a clear pattern of the seasonal incidence of different respiratory tract infections emerged. Over 70% of the total number of reported adenovirus infections, over 80% of the parainfluenza virus infections, and over 90% of the RS virus infections were in children. M. pneumoniae infections were most frequently reported in adults. Influenza A virus infection was predominant in the adult population, with a high proportion in those aged 60 years and over. Influenza B infections were reported equally in adults and children, but over one third were in children of school age. The proportion of lower respiratory infections to total respiratory infections varied from one virus to another, and ranged from less than half for adenovirus to over four fifths for mycoplasma infections. Nonlocalizing fever was usually the second principal clinical condition reported in association with respiratory viruses.",,"['Assaad, F.', 'Cockburn, W. Chas.']",,,,
,PMC,Whither virology? Trends and prospects in medical research.,,PMC2495514,,,,,"Stuart-Harris, C.",,,,
,PMC,A survey of calves treated for calf diarrhea at the Ontario Veterinary College 1966-1971.,,PMC1696297,,,,,"['Larouche, Y', 'Black, W D']",,,,
,PMC,An outbreak of common colds at an Antarctic base after seventeen weeks of complete isolation,,PMC2130424,,,Six of 12 men wintering at an isolated Antarctic base sequentially developed symptoms and signs of a common cold after 17 weeks of complete isolation. Examination of specimens taken from the men in relation to the outbreak has not revealed a causative agent.,,"['Allen, T. R.', 'Bradburne, A. F.', 'Stott, E. J.', 'Goodwin, C. S.', 'Tyrrell, D. A. J.']",,,,
,PMC,"Isolation and Preliminary Characterization of the RNA-Containing R-Type, Virus-Like Particle of BHK-21 Cells",,PMC356749,,,"An R-type virus-like particle (VLP) has been isolated from the medium of BHK-21-F cells by ultracentrifugation and polyethylene glycol precipitation. The R-type VLP contains RNA which sediments at 60 to 70S in sucrose density gradients and has a molecular weight of approximately 10(7), as estimated by gel electrophoresis. The R-type VLP can be labeled with (3)H-uridine in the presence of actinomycin D. On the basis of morphology, site of maturation, and preliminary biochemical characterization, the R-type VLP does not appear to fit into any of the major groups of animal viruses.",,"['Albu, Evelyn', 'Holmes, Kathryn V.']",,,,
,PMC,In Vitro Antiviral Activity and Preliminary Clinical Trials of a New Adamantane Compound,,PMC444570,,,"A compound, 1′-methyl spiro (adamantane-2,3′-pyrrolidine) maleate, chemically related to the antiviral drug amantadine, was tested for activity in vitro against a number of human respiratory viruses. By a variety of techniques, it was shown to be active against a wide range of human and animal influenza A viruses. The effect was, however, variable and ranged from high activity against two 1957 Asian strains to no observable activity against a 1971 strain. Like amantadine, the drug did not inhibit the growth of influenza B viruses. It was also inactive against a number of paramyxoviruses. Unlike amantadine, the drug did inhibit rhinoviruses, but to a lesser extent than myxoviruses. The coronavirus 229E was also sensitive to the action of the drug in vitro. Although an earlier trial in volunteers showed that, when given orally from 2 days before until 5 days after virus challenge, the drug was protective against infection with influenza A/Hong Kong/68 virus, a similar trial in volunteers challenged with rhinoviruses 2 and 9 revealed no useful activity against rhinoviruses in man.",,"['Mathur, Asha', 'Beare, A. S.', 'Reed, Sylvia E.']",,,,
,PMC,Outline of Veterinary Virology,,PMC1319800,,,,,"Derbyshire, J. B.",,,,
,PMC,"Antiviral Effects of Aphidicolin, a New Antibiotic Produced by Cephalosporium aphidicola",,PMC444544,,,"Aphidicolin is an antibiotic of novel structure produced by the mold Cephalosporium aphidicola. It is a potent inhibitor of cellular deoxyribonucleic acid synthesis, and it also strongly inhibits the growth of herpes simplex virus both in tissue culture and in the rabbit eye. Aphidicolin is active against iododeoxyuridine-resistant herpes virus, and does not itself readily induce the formation of drug-resistant strains of herpesvirus.",,"['Bucknall, R. A.', 'Moores, H.', 'Simms, R.', 'Hesp, B.']",,,,
,PMC,Experimental Mycoplasma pulmonis Infection in Pathogen-Free Mice: Models for Studying Mycoplasmosis of the Respiratory Tract,,PMC1903941,,,"Mice of a Swiss substrain, reared under rigid pathogen-free (PF) conditions, were inoculated intranasally with broth cultures of Mycoplasma pulmonis ranging in dose from 10(1) to 9 × 10(9) colony forming units (CFU). A highly reproducible disease resulted with an LD(50) of 1.3 × 10(8) CFU and a PD(50) (dose producing pneumonia in 50% of mice) of 3.4 × 10(5) CFU. The inoculating dose of M pulmonis was found to be the critical determinant of the severity, duration and pathologic character of the respiratory disease produced. PF mice given 10(4) CFU or less developed a transient illness characterized by low frequencies of rhinitis, otitis media, laryngotracheitis and focal pneumonia. This was proposed as a low dose model. Doses of 10(5) to 10(9) CFU resulted in high frequencies of rhinitis, otitis media, laryngotracheitis and pneumonia. Within the first 10 days the pneumonia often was fatal, being characterized by an outpouring of neutrophils and edema fluid into alveolar spaces, pulmonary congestion and hemorrhage and, occasionally, pleuritis. This high dose—acute disease model was shown to be the result of seeding alveoli with large numbers of organisms at the time of intranasal inoculation. In animals surviving doses of 10(5) to 10(9) CFU beyond approximately 10 days postinoculation, the larger concentration of organisms was present in bronchi and bronchioles, giving rise to a third model, the high dose—chronic disease model. The predominant lesions were chronic suppurative bronchitis and bronchiolitis, marked peribronchial lymphoid cuffing, variable numbers of neutrophils and macrophages in alveoli, and complications such as bronchiectasis and pulmonary abscesses. Identical lesions were observed in axenic mice infected with M pulmonis. The infection in PF mice is considered a highly useful experimental system, both for comparative study of respiratory mycoplasmosis and for investigations directed toward understanding and eliminating the natural disease this agent causes in conventional mice and rats.",,"['Lindsey, J. Russell', 'Cassell, Gail H.']",,,,
,PMC,Alternate immunoprophylactic and biologic techniques in the control of viral respiratory tract diseases.,,PMC1455052,,,,,"Geme, J W",,,,
,PMC,Infectious diseases: annual review of significant publications.,,PMC2495868,,,,,"Reimann, H. A.",,,,
,PMC,Effect of Isoprinosine Against Challenge with A(H(3)N(2))/Hong Kong Influenza Virus in Volunteers,,PMC444443,,,"Volunteers were challenged with A(H(3)N(2))/Hong Kong/8/68 influenza virus while being given prophylaxis with either isoprinosine or placebo in a double-blind experiment. Isoprinosine, which had demonstrable antiviral activity in animal models, did not appear to protect humans from clinical influenza. The only beneficial effect of the drug observed was a slight, but significant, reduction in virus shedding.",,"['Longley, Selden', 'Dunning, R. Lynn', 'Waldman, Robert H.']",,,,
,PMC,Electron Microscopy of Intestinal Epithelial Cells of Piglets Infected with a Transmissible Gastroenteritis Virus,,PMC1319749,,,"An electron microscopic study of intestinal epithelial cells of neonatal piglets infected with transmissible gastroenteritis (TGE) virus revealed a unique parasite-host cell interaction. Entry of the TGE virus into intestinal epithelial cells of newborn piglets is mediated through a network of cytoplasmic tubules of plasmalemma origin. the tubules, called microcanaliculi, are morphologically distinct from endoplasmic reticulum and Golgi. In uninfected animals similar tubules appear to be responsible for the indiscriminate uptake of large quantities of macromolecules from colostrum during the first few days of life. Thin-section profiles of plasmalemma invaginations resembled tubules or canals and frequently contained viral particles. TGE viral particles developed and accumulated within cytoplasmic vacuoles. Initially the vacuoles were continuous with the microcanaliculi formed by deep plasmalemma invagination. Mature viral particles were 60 to 85 mu in diameter with an electron dense doughnut-shaped nucleoid surrounded by a trilaminar membrane which resembled the vacuolar wall. Abundant evidence of viral effects was observed in absorbtive epithelial cells of the jejunum and ileum but not of the duodenum. The ability of absorbtive intestinal epithelial cells to form deep cytoplasmic tubular invaginations is temporally related to the pathogenesis of TGE and may explain in part why pigs usually are fatally affected by TGE only during the neonatal period.",,"['Wagner, J. E.', 'Beamer, P. D.', 'Ristic, M.']",,,,
,PMC,Age Dependent Resistance to Transmissible Gastroenteritis of Swine (TGE) II. Coronavirus Titer in Tissues of Pigs After Exposure,,PMC1319747,,,"Coronavirus titers were compared in various tissues of three-day old and 21-day old pigs after exposure to the virus of transmissible gastroenteritis (TGE). Pigs in both groups that did not die from TGE were necropsied at intervals from one to 15 days post-exposure, and their tissues assayed for viral content. Viral titers were much higher in the small intestines of the younger pigs. Viral isolations were obtained from several tissues of the younger pigs but only from the small intestines of pigs infected at 21 days of age. Levels of viral neutralizing antibodies in the serums of both age groups were comparable at similar post-exposure intervals.",,"['Norman, J. O.', 'Lambert, G.', 'Moon, H. W.', 'Stark, S. L.']",,,,
,PMC,Age Dependent Resistance to Transmissible Gastroenteritis of Swine (TGE) I. Clinical Signs and Some Mucosal Dimensions in Small Intestine,,PMC1319746,,,"Pigs were exposed to transmissible gastroenteritis (TGE) virus when three days old or when 21 days old. Diarrhea was earliest in onset, most frequent, most profuse and most prolonged in the youngest group. Pigs exposed when three days old also had a higher case fatality rate than those exposed when 21 days old. The histological response of both groups to exposure was atrophy of villi and hyperplasia of crypts in jejunum and ileum. However, from days three to seven post-exposure, when most fatalities occurred in the younger group, atrophy of villi was both more intensive and extensive in the younger group. Hyperplasia of crypts was also greater and more prolonged in the younger group. Regeneration of atrophic villi was more rapid in jejunum than ileum in both groups. Results were interpreted to indicate two populations, with different rates of regeneration, in the 21-day old group. Based on this interpretation, regeneration of villi was more rapid in one population from the 21-day old group than in the three-day old group. The length of villi and depth of crypts in control pigs varied longitudinally (i.e. from site to site) in the intestine, within each age group. Length of villi and depth of crypts in control pigs also varied with age.",,"['Moon, H. W.', 'Norman, J. O.', 'Lambert, G.']",,,,
,PMC,Purification and Properties of a Glycoprotein Acid Phosphatase from Candida albicans,,PMC251763,,,"An acid phosphomonoesterase was purified 87-fold with a 4% recovery from disintegrated cells of Candida albicans by four stages of column chromatography. The purified enzyme was homogeneous by ultracentrifugal, electrophoretic, and immunological analyses. The fully corrected sedimentation coefficient, s(20,w), was calculated to be 5.51s. Molecular weight estimated from ultracentrifugal data was 124.3 × 10(3), from gel chromatography was 115 × 10(3), and from acrylamide gel electrophoretic data was 131 × 10(3). Buoyant density in sucrose was 1.15 g/cm(3). The enzyme was a mannoprotein with a hexose to protein ratio of 7: 1. The Michaelis constant of the enzyme was 3.3 × 10(−4) M for p-nitrophenyl phosphate as substrate, and the pH optimum was 4.5. The enzyme was competitively inhibited by inorganic phosphate (K(i) = 10(−4) M) and by arsenate (K(i) = 0.5 × 10(−4) M). A wide range of inorganic cations and anions did not affect enzyme activity, but Hg(2+), Cd(2+), and Cu(2+) were inhibitory. F(−) was also inhibitory at low concentrations, but the effect was reversed at higher concentrations. Phosphatase activity was completely destroyed by exposure of the enzyme to 70 C for 12 min, but was destroyed only slowly by proteolytic hydrolysis. The purified glycoprotein enzyme gave a line of identity with the “b” antigen of crude C. albicans homogenates in immunodiffusion and immunoelectrophoresis tests with sera from rabbits inoculated with intact C. albicans cells and from humans with proven candidiasis. Preliminary evidence suggests that the mannan and not the protein portion of the enzyme molecule is responsible for this antigenicity.",,"['Odds, Frank C.', 'Hierholzer, John C.']",,,,
,PMC,Electron microscopic study of the distribution of the Australia antigen in individual sera of 50 serologically positive blood donors and two patients with serum hepatitis,,PMC477687,,,The distribution of the morphological types of Australia antigen in 50 blood donors and two patients with serum hepatitis is described. The significance of the high incidence of immune complexes and Dane particles in these persistent carriers is discussed.,,"['Stannard, Linda M.', 'Moodie, J.', 'Keen, G. A.', 'Kipps, A.']",,,,
,PMC,Detection of Coronavirus Strain 692 by Immune Electron Microscopy,,PMC422645,,,Utilization of the technique of immune electron microscopy has enabled the detection of a coronavirus in organ culture harvests derived from a washing from an adult with an acute upper respiratory tract illness; convalescent serum was the source of specific antibody.,,"['Kapikian, Albert Z.', 'James, Harvey D.', 'Kelly, Sara J.', 'Vaughn, Annie L.']",,,,
,PMC,Detection of Coronavirus 229E Antibody by Indirect Hemagglutination,,PMC380648,,,"Tannic-acid treated sheep erythrocytes (fresh or glutaraldehyde preserved) were sensitized with 229E antigens from human embryonic lung (RU-1) cell cultures. Indirect hemagglutination (IHA) antigen titers in 229E-infected cell cultures paralleled virus infectivity and complement fixation (CF) antigen titers. The identity of the IHA antigen was confirmed by testing extracts from inoculated and control cell cultures for ability to inhibit IHA. Also, significant increases in IHA antibody were demonstrated with acute and convalescent serum pairs from patients with proven 229E infections. A comparison of IHA, neutralization and CF titers for 229E antibodies was made on human sera drawn from different populations. The IHA and neutralization results were in agreement on 93% of the 129 sera found to be positive by at least one of three tests. The number of antibody titers detected by the CF test was insufficient to permit comparison. Hyperimmune sera from animals immunized with OC 43 did not react with 229E by IHA. Also no increase in IHA antibody was demonstrated with acute and convalescent serum pairs from patients with seroconversions to OC 43. These findings suggest that the IHA test provides (i) a rapid and sensitive method for serodiagnosis of 229E infections and (ii) a simple and inexpensive method for seroepidemiological studies.",,"['Kaye, Harold S.', 'Ong, Suat Bee', 'Dowdle, Walter R.']",,,,
,PMC,Visualization by Immune Electron Microscopy of a 27-nm Particle Associated with Acute Infectious Nonbacterial Gastroenteritis,,PMC356579,,,"A 27-nm particle was observed by immune electron microscopy in an infectious stool filtrate derived from an outbreak in Norwalk, Ohio, of acute infectious nonbacterial gastroenteritis. Both experimentally and naturally infected individuals developed serological evidence of infection; this along with other evidence suggested that the particle was the etiological agent of Norwalk gastroenteritis.",,"['Kapikian, Albert Z.', 'Wyatt, Richard G.', 'Dolin, Raphael', 'Thornhill, Thomas S.', 'Kalica, Anthony R.', 'Chanock, Robert M.']",,,,
,PMC,Studies on the Hemagglutination Phenomenon of Hemagglutinating Encephalomyelitis Virus (HEV) of Pigs,,PMC1319700,,,"Hemagglutinating encephalomyelitis virus (HEV), unlike other Coronaviruses, readily agglutinates a variety of red blood cells. The reaction differs from that of the Myxovirus/Paramyxovirus groups in several respects. Unlike the Myxoviruses, HEV agglutinated red cells treated with receptor destroying enzyme. No neuraminidase activity was demonstrated with HEV and there was no apparent elution of the virus from agglutinated cells. Mucins and animal sera inhibited the agglutination reaction markedly. Ultra violet light exposure sufficient to destroy infectivity had no effect on hemagglutination. Density gradient studies showed that the hemagglutinin was closely associated with the virus particle.",,"['Greig, A. S.', 'Bouillant, A. M. P.']",,,,
,PMC,Enhanced Growth of a Murine Coronavirus in Transformed Mouse Cells,,PMC422565,,,"Plaque formation by A59 virus, a murine coronavirus, was facilitated in AL/N and Balb mouse cells transformed by polyoma virus, simian virus 40, murine sarcoma virus, or mammary tumor virus. In these virus-transformed cells, A59 virus plaques were larger, they appeared earlier, and plaquing efficiencies were higher than in normal, untransformed cells. “Spontaneously” transformed AL/N cells behaved similarly to untransformed cells, whereas “spontaneously” transformed Balb cells resembled virus-transformed cell hosts. Both untransformed and transformed AL/N and Balb cells were permissive hosts for A59 virus. However, multiplication of A59 virus was enhanced at least fivefold in the virus-transformed AL/N cell hosts. Larger differences (100-fold or greater) in A59 virus production were obtained during the first cycle of infection in Balb cells at low multiplicities and in AL/N cells after multiple cycles of virus growth. In virus-transformed and “spontaneously” transformed Balb cells, A59 virus induced extensive syncytia formation.",,"['Sturman, Lawrence S.', 'Takemoto, Kenneth K.']",,,,
,PMC,"Antibody Responses in Serum, Colostrum, and Milk of Swine After Infection or Vaccination with Transmissible Gastroenteritis Virus",,PMC422530,,,"The antibody response of pregnant swine to transmissible gastroenteritis (TGE) virus was studied, with special reference to the titers and the immunoglobulin (Ig) class of TGE neutralizing antibodies in colostrum and milk. Animals vaccinated twice intramuscularly or intramammarily with live attenuated TGE virus developed high levels of antibodies in serum and colostrum, but the levels in milk declined markedly within a few days post-farrowing. In contrast, animals naturally or experimentally infected with virulent virus generally developed lower levels of antibodies in serum and colostrum but maintained higher levels in milk, as compared to the vaccinated animals. Gel filtration studies indicated that antibodies in milk from vaccinated animals were primarily of the IgG class, whereas those from the naturally or experimentally infected animals were primarily of the IgA class. The ability of sows to transmit a high degree of passive immunity to their suckling progeny was more closely associated with TGE antibodies of the IgA than the IgG class. Present evidence suggests that high levels of TGE antibodies of the IgA class occur in milk as a result of an infection of the intestinal tract. Probable reasons for this are discussed.",,"['Bohl, Edward H.', 'Gupta, R. K. Paul', 'Olquin, M. V. Fernando', 'Saif, Linda J.']",,,,
,PMC,"Respiratory disease in a colony of rats: II. Isolation of Mycoplasma pulmonis from the natural disease, and the experimental disease induced with a cloned culture of this organism",,PMC2130201,,,"Mycoplasma pulmonis was isolated from the pneumonic lung of a rat. Two groups of mycoplasma-free rats were inoculated, one with a culture of the M. pulmonis strain which had been cloned four times (group A) and the other with a lung homogenate of the rat from which the strain had been isolated (group B). A third group (C) consisted of uninoculated control animals. Each group was kept in strict isolation and allowed to breed so that the progeny was naturally exposed to any pathogens present in the inoculated animals. After different periods of exposure, rats were autopsied, respiratory tracts and inner ears were cultured for mycoplasmas and bacteria, and sera were tested for complement-fixing antibodies to murine mycoplasmas. In group-A rats, M. pulmonis was consistently isolated from the inner ears or lungs from 50 to 715 days after exposure. Complement-fixing antibody to M. pulmonis was detected 20 days after inoculation, but in the naturally exposed progeny antibody took longer than 50 days to develop. Antibodies to the other known mycoplasmas of murine origin, M. arthritidis and M. neurolyticum, were never found. Purulent otitis interna was consistently found from day 55 onwards, while lung lesions were first observed at 85 days and persisted to 715 days. Pulmonary lesions developed more slowly in inoculated parents than in exposed progeny. Similar results were found in group-B rats, which were examined up to 441 days after inoculation. Uninoculated group-C rats were examined up to 768 days of age, but M. pulmonis was not recovered; of the 54 animals whose serum was tested all were negative to the three species of mycoplasmas, except one which had a titre of 16 with M. pulmonis. Pneumonia, bronchiectasis or lymphoreticular hyperplasia were not seen in any of these control rats. Bacterial respiratory pathogens were not isolated from rats in any of the groups, nor was antibody to Sendai virus detected. The results suggest that M. pulmonis alone can cause pneumonia and bronchiectasis in rats since mechanical carry-over of another pathogen with the initial cloned inoculum is very unlikely and there was no evidence for the participation of any other rat pathogen. The respiratory disease induced by the cloned culture was comparable with that induced by the lung homogenate, and with the well-known syndrome of chronic respiratory disease and bronchiectasis in the rat.",,"['Whittlestone, P.', 'Lemcke, Ruth M.', 'Olds, R. J.']",,,,
,PMC,The isolation of influenza viruses,,PMC477370,,,"Of 129 strains of the Hong Kong variant of influenza A2 virus isolated from 176 respiratory infections, 105 (81·4%) were isolated in tissue culture, the remainder being detected only by the inoculation of fertile hen's eggs. Organ cultures of chick embryo trachea were at least as sensitive as monkey kidney tissue culture for the isolation of this virus but organ cultures of human embryonic ciliated epithelium were much less efficient. The reverse was true for strains of influenza B virus studied in 1970 and 1971 when eggs and chick embryo tracheal organ culture were of little value and organ cultures of human embryonic ciliated epithelium and monkey kidney tissue cultures were the systems of choice.",,"['Higgins, P. G.', 'Ellis, Eileen M.']",,,,
,PMC,Coronavirus antibody titres in sera of healthy adults and experimentally infected volunteers,,PMC2130035,,,"Six coronaviruses isolated in the U.S.A. have been inoculated into volunteers and all produced colds. Between 10 and 20% of infected volunteers developed heterologous antibody responses after these and other experimental infections with coronaviruses. The haemagglutination-inhibition test with the OC43 virus strain was found to detect antibody rises after infection with a variety of strains. Studies on normal adult sera taken between 1965 and 1970 revealed a high frequency of neutralizing antibody to one strain (229 E) and a frequency of HI antibody to strain OC43 which fluctuated from year to year. Complement-fixing antibodies to these two viruses were also found, revealing an apparent increase in the activity of coronaviruses in the general population of the U.K., during the winter of 1968-9.",,"['Bradburne, A. F.', 'Somerset, B. A.']",,,,
,PMC,Infectious diseases: annual review of significant publications.,,PMC2495223,,,,,"Reimann, H. A.",,,,
,PMC,Polykaryocytosis and Replication of Mouse Hepatitis Virus in Peritoneal Macrophages,,PMC2072535,,,"Results of this investigation indicated that the infectivity titre of mouse hepatitis virus decreased after 6 hour incubation at 37°. Nutrient fluids from infected macrophage cultures retained pathogenicity in vivo and the ability to form polykaryons in vitro. Electron microscope studies of polykaryons formed from infected macrophage cultures showed the presence of virus-like particles in the cytoplasm. From the study, it was concluded that polykaryon formation in infected macrophage cultures resulted from an active viral agent.",,"['Lewis, Lenore', 'Starr, Theodore J.']",,,,
,PMC,Ultrastructural features of antigens associated with human hepatitis.,,PMC1945139,,,,,"Zuckerman, A. J.",,,,
,PMC,Electron Microscope Methods for the Identification of Adenoviruses Isolated in Micro Tissue Cultures,,PMC380292,,,"A tissue culture micromethod is described for adenovirus isolation and preparation for presumptive identification by electron microscopy. These procedures are easier, more economical, and faster than conventional methods. The micro techniques make it more feasible to utilize direct visualization of virus in infected cells as an adjunctive diagnostic and research tool.",,"['Rosenbaum, M. J.', 'Kory, R. C.', 'Siegesmund, K. A.', 'Pedersen, H. J.', 'Sullivan, E. J.', 'Peckinpaugh, R. O.']",,,,
,PMC,Rapid Diagnosis by Electron Microscopy of Avian Coronavirus Infection,,PMC1319581,,,"The election microscopic examination of allantoic fluid from embryonated hens' eggs inoculated with tissue homogenates from organs of birds suffering with infectious bronchitis, reveals the presence of coronaviruses as early as the first or the second passage. This method permits a rapid diagnosis and is as accurate as the standard technique.",,"['Marsolais, G.', 'Berthiaume, L.', 'DiFranco, E.', 'Marois, P.']",,,,
,PMC,Research complications due to Haemobartonella and Eperythrozoon infections in experimental animals.,,PMC2047626,,,,,"['Baker, H. J.', 'Cassell, G. H.', 'Lindsey, J. R.']",,,,
,PMC,Murine chronic respiratory disease. Significance as a research complication and experimental production with Mycoplasma pulmonis.,,PMC2047606,,,,,"['Lindsey, J. R.', 'Baker, H. J.', 'Overcash, R. G.', 'Cassell, G. H.', 'Hunt, C. E.']",,,,
,PMC,The multiple aetiology of viral hepatitis,,PMC2467204,,,Infectious hepatitis is epidemiologically and immunologically distinct from serum hepatitis. The Australia antigen is related more specifically to serum hepatitis. The possible role of coronavirus—and paramyxovirus-like particles in the aetiology of some infections of the liver in man and in marmosets inoculated with human infectious hepatitis material is discussed and the difficulties in the interpretation of the currently available data are emphasized. The recent studies in Melbourne of a faecal antigen found in some patients with infectious hepatitis and the discovery of an antiserum in Milan which reacted with an antigen associated with epidemic hepatitis are discussed. Mention is made of the recent isolation in Detroit-6 cells of virus-like particles from patients with infectious hepatitis. It is concluded that viral hepatitis is an infection of multiple aetiology and that the successful cultivation in vitro of the agent or agents of hepatitis remains the outstanding and most urgent problem.,,"Zuckerman, A. J.",,,,
,PMC,Studies of respiratory viruses in personnel at an Antarctic base,,PMC2130878,,,"Thirteen men wintering on an Antarctic base were isolated from other human contact for 10 months. During this period Coxsackievirus A21 and later influenza A2 virus were administered to some of the men. Serum samples were collected from each of the men at monthly intervals. Coxsackievirus A21 produced symptoms and apparently spread to uninoculated men. It also appears that repeated re-infections occurred and that the virus persisted in this small community for most of the period of isolation. HI antibody responses in the absence of neutralizing antibody responses seem to be transient. The vaccine strain of influenza virus induced antibody responses but did not cause symptoms. There was no evidence of spread to uninoculated men. Antibody titres against influenza C, parainfluenzaviruses 1 and 2 and coronavirus OC43 did not fall significantly during isolation. An outbreak of respiratory illness occurred at the end of isolation and its origin was traced. No causative agent was detected.",,"['Holmes, M. J.', 'Allen, T. R.', 'Bradburne, A. F.', 'Stott, E. J.']",,,,
,PMC,Infectious diseases: annual review of significant publications.,,PMC2466919,,,,,"Reimann, H. A.",,,,
,PMC,Infective hepatitis and the handling of specimens in general practice.,,PMC2156316,,,,,"Marmion, B. P.",,,,
,PMC,The role of Australia antigen.,,PMC1930761,,,,,,,,,
,PMC,Cirrhosis Associated with the Australia Antigen in an Infant Who Acquired Hepatitis from Her Mother,,PMC1820311,,,"A 19-week-old English girl developed acute viral hepatitis, which became chronic with persistent hepatosplenomegaly and abnormal liver function tests. Liver biopsy at 1 year showed an active cirrhosis with multinucleated giant cells. The Australia (Au) antigen was detected repeatedly in the infant's serum by immunodiffusion and by electron microscopy at the time of the acute attack and during the development of cirrhosis. She had apparently acquired the hepatitis from her mother, who had had jaundice at the end of pregnancy and for one month thereafter, and who was subsequently shown to be a carrier of Au antigen. Particles with surface projections resembling paramyxoviruses were observed in two of the later specimens of the infant's serum.",,"['Wright, Ralph', 'Perkins, J. R.', 'Bower, B. D.', 'Jerrome, D. W.']",,,,
,PMC,Viruses associated with acute respiratory infections in Royal Air Force personnel,,PMC2130859,,,"All respiratory illnesses which were reported to the medical officers between September 1966 and December 1967 on a Royal Air Force station of 350 men were studied virologically. Three periods of increased respiratory infections were observed: two occurred in the autumn, one in each year, and the third in the winter during January and February. The autumnal outbreaks were associated mainly with rhinovirus infections, and high isolation rates (82·1, 65·9%) were achieved at these times. Few of the illnesses during the winter outbreak could be diagnosed in the laboratory, and no evidence was found of infection with `coronaviruses'. Despite the entrance of 30 fresh recruits direct from civilian life every 5 weeks, the respiratory infections encountered on the station were very similar to those in the local population and were not predominantly infections with adenoviruses, Coevirus, and Mycoplasma pneumoniae, as previously reported from larger military recruit centres.",,"['Higgins, P. G.', 'Ellis, Eileen M.', 'Woolley, D. A.', 'Cassidy, P. F.']",,,,
,PMC,Review: antigens and viruses in acute hepatitis.,,PMC1712859,,,,,"['Zuckerman, A J', 'Taylor, P E', 'Bird, R G']",,,,
,PMC,Genetic Aspects of Viral Diseases: The Lilly Lecture 1970,,PMC5366631,,,,,"Fenner, F. J.",,,,
,PMC,Viruses and immunosuppressant drugs.,,PMC1701623,,,,,"Sirtori, C",,,,
,PMC,Australian Antigen and Autoantibodies in Chronic Hepatitis,,PMC1700632,,,"The sera of 110 patients with chronic hepatitis and adequate controls were examined for antibodies to smooth muscle (S.M.), mitochondria (M.), and for antinuclear factors by the immunofluorescence method, and for Australia (Au(1)) antigen by a modified micro-Ouchterlony immunodiffusion technique. Twelve out of 13 patients with primary biliary cirrhosis had M. antibodies, two had antinuclear factor, and none had Au(1) in their sera. In chronic aggressive hepatitis 23·5% of the sera contained antinuclear factor, 13% S.M. antibodies, 10·5% M. antibodies, and 22% Au(1) antigen. Of the 12 patients with chronic persistent hepatitis, one had antinuclear factor, one S.M. antibodies, and three Au(1) antigen. The most striking finding was a mutual exclusion between Au(1) antigen and M. and S.M. antibodies. None of the 33 patients with one or the other form of chronic hepatitis and M. or S.M. antibodies had Au(1) antigen; 22 out of 77 (28%) patients without such antibodies were positive.",,"Vischer, T. L.",,,,
,PMC,Presence of Particles other than the Australia-SH Antigen in a Case of Chronic Active Hepatitis with Cirrhosis,,PMC1699390,,,"Examination of serum specimens from a patient with chronic active hepatitis proved negative to the Australia-SH antigen by immunodiffusion and by complement fixation. Because the sera were anticomplementary they were examined with the electron microscope, and virus-like structures similar to members of the coronavirus group were identified. The possible significance of this finding in human serum and its relation to mouse hepatitis virus are discussed. A sample of the serum pool containing the MS-1 agent was found negative when examined by immunodiffusion, complement fixation, and electron microscopy. The possible lack of immunological identity between infectious and serum hepatitis is discussed.",,"['Zuckerman, A. J.', 'Taylor, Patricia E.']",,,,
,PMC,Australia antigen and hepatitis.,,PMC1699357,,,,,,,,,
,PMC,Viral hepatitis and tests for the Australia (hepatitis-associated) antigen and antibody,,PMC2427559,,,"”Australia” antigen has been shown to be closely associated with serum hepatitis. The presence of the antigen and its corresponding antiserum can be detected in human beings (and in certain primates) by a number of laboratory tests. This is of great potential importance to blood transfusion and similar services because detection and exclusion of blood donors carrying the antigen might significantly reduce the risk of hepatitis from transfusions and other procedures. In this paper the present state of knowledge of ”Australia” or ”hepatitis-associated” antigen is reviewed. The currently employed tests are described in detail and their use, interpretation and limitations are discussed. Though it appears from early studies that the application of routine screening tests to blood donors would only reduce the risk to recipients by less than 25%, the more sensitive tests becoming available may increase this percentage and it is recommended that where competent laboratory services are available steps should be taken to set up a scheme for testing donors—provided that the current limitations of such a scheme are clearly recognized.",,,,,,
,PMC,Standardized Viral Hemagglutination and Hemagglutination-Inhibition Tests. II. Description and Statistical Evaluation,,PMC378095,,,"Standardized hemagglutination and hemagglutination-inhibition procedures are described and statistically evaluated for all animal viruses where applicable, except for rubella and the arbovirus group. The standardized tests employ a constant phosphate-buffered saline diluent and constant volumes of serum, antigen, and standardized erythrocyte suspension. The standardized hemagglutination test has a reproducibility of 84 to 96% with adenoviruses, rubeola, and the myxoviruses, and 78 to 93% with reoviruses; the standardized hemagglutination-inhibition test has a reproducibility of 95 to 100% with all viruses tested.",,"['Hierholzer, John C.', 'Suggs, Morris T.', 'Hall, Elmer C.']",,,,
,PMC,The General Practitioner and the Virus Laboratory,,PMC1810642,,,,,"Higgins, P G",,,,
,PMC,Relationship of Phagocytic Activity to Pathogenicity of Mouse Hepatitis Virus as Affected by Triolein and Cortisone,,PMC2072135,,,"The pathogenicity of mouse hepatitis virus (MHV-1) was studied following treatment with triolein and cortisone which, respectively, stimulated and suppressed phagocytic activity of the reticuloendothelial system (RES) as measured by clearance of colloidal carbon. When inoculated i.p., triolein moderately enhanced RES activity of germfree mice, while exerting no significant effect in conventional mice. In both groups of mice, however, protection was found against an i.p. challenge of virus. Cortisone greatly suppressed RES activity and significantly increased susceptibility of germfree and conventional mice to MHV-1. Triolein also was found to protect mice against the combined challenge of cortisone plus virus. However, triolein, whether injected i.p. or i.v., failed to protect against an i.v. challenge of virus. These data support two conclusions: (1) triolein exerted its protective effect at some site other than the macrophages of the liver; (2) protection against MHV-1 infection following triolein treatment was not related to the carbon clearing activity of the RES.",,"['Lavelle, G. C.', 'Starr, T. J.']",,,,
,PMC,Virus prevalence in Scotland.,,PMC2635177,,,,,"Grist, N. R.",,,,
,PMC,Effects of corticosteroids on mouse hepatitis virus infection.,,PMC1552950,,,,,"['Datta, D V', 'Isselbacher, K J']",,,,
,PMC,Mouse hepatitis virus (MHV3) infection in chronic murine schistosomiasis mansoni.,,PMC1750354,,,,,"['Warren, K S', 'Rosenthal, M S', 'Domingo, E O']",,,,
,PMC,"Activity of nicotinamide–adenine dinucleotide pyrophosphorylase in liver nuclei. Effects of partial hepatectomy, hepatotoxins and dietary changes",,PMC1198772,,,"1. The activity of NAD pyrophosphorylase is lower in nuclei isolated from regenerating rat liver than in normal nuclei, and this is due to leakage of the enzyme from the nuclei during the isolation. 2. The NAD pyrophosphorylase activity is lower in liver nuclei from newborn rats, and from rats on a protein-free diet, but no leakage occurs in these cases. 3. Poisoning with α-amanitin brings about a transient enhancement of NAD pyrophosphorylase activity in mouse liver nuclei. 4. No changes of enzyme activity were observed after 72hr. starvation, administration of actinomycin D or infection with MHV3 virus.",,"['Stirpe, F.', 'Corte, E. Della']",,,,
,PMC,"Growth in suckling-mouse brain of ""IBV-like"" viruses from patients with upper respiratory tract disease.",,PMC223830,,,,,"['McIntosh, K', 'Becker, W B', 'Chanock, R M']",,,,
,PMC,"Electron microscopy of the hepatocellular and Kupffer-cell lesions of mouse hepatitis, with particular reference to the effect of cortisone.",,PMC1965313,,,,,"['Ruebner, B. H.', 'Hirano, T.', 'Slusser, R. J.']",,,,
,PMC,The induction of hepatitis by prior partial hepatectomy in resistant adult rats injected with H-1 virus. Light and electron microscopy and virologic studies.,,PMC1907275,,,,,"['Ruffolo, P. R.', 'Margolis, G.', 'Kilham, L.']",,,,
,PMC,Electron micrographic features of acute murine reovirus hepatitis.,,PMC1920454,,,,,"Papadimitriou, J. M.",,,,
,PMC,Effect of certain murine pathogens on phagocytic activity.,,PMC2094603,,,,,"['Gledhill, A. W.', 'Bilbey, D. L.', 'Niven, J. S.']",,,,
,PMC,EFFECT OF CORTISONE ON GENETIC RESISTANCE TO MOUSE HEPATITIS VIRUS IN VIVO AND IN VITRO,,PMC300229,,,,,"['Gallily, Ruth', 'Warwick, Anne', 'Bang, Frederik B.']",,,,
,PMC,The Effect of a Murine Hepatitis Virus on the Liver: An Anatomic and Histochemical Study,,PMC1949530,,,,,"['Jones, Wallace A.', 'Cohen, Richard B.']",,,,
,PMC,The Interference of Mouse Hepatitis Virus with Ectromelia in Mice and a Possible Explanation of its Mechanism,,PMC2083466,,,,,"Gledhill, A. W.",,,,
,PMC,INTERFERENCE BETWEEN INFLUENZA VIRUS AND INFECTIOUS BRONCHITIS VIRUS OF CHICKENS,,PMC169263,,,,,"['Groupé, Vincent', 'Pugh, Leonora H.']",,,,
,PMC,Infectious Bronchitis and Newcastle Disease,,PMC1791257,,,,,"Beaudette, F. R.",,,,
f056da9c64fbf00a4645ae326e8a4339d015d155,biorxiv,SIANN: Strain Identification by Alignment to Near Neighbors,doi.org/10.1101/001727,,,See https://www.biorxiv.org/about-biorxiv,"Next-generation sequencing is increasingly being used to study samples composed of mixtures of organisms, such as in clinical applications where the presence of a pathogen at very low abundance may be highly important. We present an analytical method (SIANN: Strain Identification by Alignment to Near Neighbors) specifically designed to rapidly detect a set of target organisms in mixed samples that achieves a high degree of species- and strain-specificity by aligning short sequence reads to the genomes of near neighbor organisms, as well as that of the target. Empirical benchmarking alongside the current state-of-the-art methods shows an extremely high Positive Predictive Value, even at very low abundances of the target organism in a mixed sample. SIANN is available as an Illumina BaseSpace app, as well as through Signature Science, LLC. SIANN results are presented in a streamlined report designed to be comprehensible to the non-specialist user, providing a powerful tool for rapid species detection in a mixed sample. By focusing on a set of (customizable) target organisms and their near neighbors, SIANN can operate quickly and with low computational requirements while delivering highly accurate results.",2014-01-10,Samuel Minot;Stephen D Turner;Krista L Ternus;Dana R Kadavy;,,,,True
daf32e013d325a6feb80e83d15aabc64a48fae33,biorxiv,Spatial epidemiology of networked metapopulation: An overview,doi.org/10.1101/003889,,,See https://www.biorxiv.org/about-biorxiv,"An emerging disease is one infectious epidemic caused by a newly transmissible pathogen, which has either appeared for the first time or already existed in human populations, having the capacity to increase rapidly in incidence as well as geographic range. Adapting to human immune system, emerging diseases may trigger large-scale pandemic spreading, such as the transnational spreading of SARS, the global outbreak of A(H1N1), and the recent potential invasion of avian influenza A(H7N9). To study the dynamics mediating the transmission of emerging diseases, spatial epidemiology of networked metapopulation provides a valuable modeling framework, which takes spatially distributed factors into consideration. This review elaborates the latest progresses on the spatial metapopulation dynamics, discusses empirical and theoretical findings that verify the validity of networked metapopulations, and the application in evaluating the effectiveness of disease intervention strategies as well.",2014-06-04,Lin WANG;Xiang Li;,,,,True
f33c6d94b0efaa198f8f3f20e644625fa3fe10d2,biorxiv,Sequencing of the human IG light chain loci from a hydatidiform mole BAC library reveals locus-specific signatures of genetic diversity,doi.org/10.1101/006866,,,See https://www.biorxiv.org/about-biorxiv,"Germline variation at immunoglobulin gene (IG) loci is critical for pathogen-mediated immunity, but establishing complete reference sequences in these regions is problematic because of segmental duplications and somatically rearranged source DNA. We sequenced BAC clones from the essentially haploid hydatidiform mole, CHM1, across the light chain IG loci, kappa (IGK) and lambda (IGL), creating single haplotype representations of these regions. The IGL haplotype is 1.25Mb of contiguous sequence with four novel V gene and one novel C gene alleles and an 11.9kbp insertion. The IGK haplotype consists of two 644kbp proximal and 466kbp distal contigs separated by a gap also present in the reference genome sequence. Our effort added an additional 49kbp of unique sequence extending into this gap. The IGK haplotype contains six novel V gene and one novel J gene alleles and a 16.7kbp region with increased sequence identity between the two IGK contigs, exhibiting signatures of interlocus gene conversion. Our data facilitated the first comparison of nucleotide diversity between the light and IG heavy (IGH) chain haplotypes within a single genome, revealing a three to six fold enrichment in the IGH locus, supporting the theory that the heavy chain may be more important in determining antigenic specificity.",2014-07-03,Corey T Watson;Karyn Meltz Steinberg;Tina A Graves-Lindsay;Rene L Warren;Maika Malig;Jacqueline E Schein;Richard K Wilson;Rob Holt;Evan Eichler;Felix Breden;,,,,True
4da8a87e614373d56070ed272487451266dce919,biorxiv,Bayesian mixture analysis for metagenomic community profiling.,doi.org/10.1101/007476,,,See https://www.biorxiv.org/about-biorxiv,"Deep sequencing of clinical samples is now an established tool for the detection of infectious pathogens, with direct medical applications. The large amount of data generated provides an opportunity to detect species even at very low levels, provided that computational tools can effectively interpret potentially complex metagenomic mixtures. Data interpretation is complicated by the fact that short sequencing reads can match multiple organisms and by the lack of completeness of existing databases, in particular for viral pathogens. This interpretation problem can be formulated statistically as a mixture model, where the species of origin of each read is missing, but the complete knowledge of all species present in the mixture helps with the individual reads assignment. Several analytical tools have been proposed to approximately solve this computational problem. Here, we show that the use of parallel Monte Carlo Markov chains (MCMC) for the exploration of the species space enables the identification of the set of species most likely to contribute to the mixture. The added accuracy comes at a cost of increased computation time. Our approach is useful for solving complex mixtures involving several related species. We designed our method specifically for the analysis of deep transcriptome sequencing datasets and with a particular focus on viral pathogen detection, but the principles are applicable more generally to all types of metagenomics mixtures. The work is implemented as a user friendly R package, available from CRAN: http://cran.r-project.org/web/packages/metaMix.",2014-10-27,Sofia Morfopoulou;Vincent Plagnol;,,,,True
eccef80cfbe078235df22398f195d5db462d8000,biorxiv,Mapping a viral phylogeny onto outbreak trees to improve host transmission inference,doi.org/10.1101/010389,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundDeveloping methods to reconstruct transmission histories for viral outbreaks could provide critical information to support locating sources of disease transmission. Phylogenetic methods used to measure the degree of relatedness among sequenced viral samples have proven useful in identifying potential outbreak sources. The complex nature of infectious disease, however, makes it difficult to assign a rigorously defined quantitative confidence value assessing the likelihood of a true direct transmission event using genetic data alone.\n\nResultsA new method is presented to calculate a confidence value assessing the likelihood of a transmission event using both phylogenetic inference and limited knowledge of incubation and infectious duration times. The method is applied to simulations of a foot and mouth disease (FMD) outbreak to demonstrate how the combination of both phylogenetic and epidemiology data can be used to strengthen the assessment of the likelihood of direct transmission over methods using just phylogenetic data or infection timing data alone. The method is applied to a previous FMD outbreak to identify areas where over confidence in previously inferred direct transmission may exist.\n\nConclusionCombining knowledge from viral evolution and epidemiology within a single integrated transmission inference framework is an important approach to assess the potential likelihood of transmission events and makes clear how specific features of a virus spread through the course of an outbreak will directly determine the potential for confidence in inferred host transmission links.",2014-11-11,Stephen P Velsko;Jonathan E Allen;,,,,True
c41fdb2efd6d61384a92a84cbba3f8233629a41b,biorxiv,The infant airway microbiome in health and disease impacts later asthma development,doi.org/10.1101/012070,,,See https://www.biorxiv.org/about-biorxiv,"The nasopharynx (NP) is a reservoir for microbes associated with acute respiratory illnesses (ARI). The development of asthma is initiated during infancy, driven by airway inflammation associated with infections. Here, we report viral and bacterial community profiling of NP aspirates across a birth cohort, capturing all lower respiratory illnesses during their first year. Most infants were initially colonized with Staphylococcus or Corynebacterium before stable colonization with Alloiococcus or Moraxella, with transient incursions of Streptococcus, Moraxella or Haemophilus marking virus-associated ARIs. Our data identify the NP microbiome as a determinant for infection spread to the lower airways, severity of accompanying inflammatory symptoms, and risk for future asthma development. Early asymptomatic colonization with Streptococcus was a strong asthma predictor, and antibiotic usage disrupted asymptomatic colonization patterns.",2014-12-02,Shu Mei Teo;Danny Mok;Kym Pham;Merci Kusel;Michael Serralha;Niamh Troy;Barbara J Holt;Belinda J Hales;Michael L Walker;Elysia Hollams;Yury H Bochkov;Kristine Grindle;Sebastian L Johnston;James E Gern;Peter D Sly;Patrick G Holt;Kathryn E Holt;Michael Inouye;,,,,True
33565294e6bc67fb7ee14dcae6cfdb08148f4ea5,biorxiv,"Big city, small world: Density, contact rates, and transmission of dengue across Pakistan.",doi.org/10.1101/018481,,,See https://www.biorxiv.org/about-biorxiv,"Macroscopic descriptions of populations commonly assume that encounters between individuals are well mixed; i.e., each individual has an equal chance of coming into contact with any other individual. Relaxing this assumption can be challenging though, due to the difficulty of acquiring detailed knowledge about the non-random nature of encounters. Here, we fitted a mathematical model of dengue virus transmission to spatial time series data from Pakistan and compared maximum-likelihood estimates of \""mixing parameters\"" when disaggregating data across an urban-rural gradient. We show that dynamics across this gradient are subject not only to differing transmission intensities but also to differing strengths of nonlinearity due to differences in mixing. We furthermore show that neglecting spatial variation in mixing can lead to substantial underestimates of the level of effort needed to control a pathogen with vaccines or other control efforts. We complement this analysis with relevant contemporary environmental drivers of dengue.",2015-04-27,Moritz U. G. Kraemer;T. Alex Perkins;Derek A.T. Cummings;Rubeena Zakar;Simon I. Hay;David L. Smith;Robert C. Reiner;,,,,True
1f9d3f9a1a0e8db6a086e0a2b5ba50cf9f235dae,biorxiv,On the causes of evolutionary transition:transversion bias,doi.org/10.1101/027722,,,See https://www.biorxiv.org/about-biorxiv,"A pattern in which nucleotide transitions are favored several-fold over transversions is common in molecular evolution. When this pattern occurs among amino acid replacements, explanations often invoke an effect of selection, on the grounds that transitions are more conservative in their effects on proteins. However, the underlying hypothesis of conservative transitions has never been tested directly. Here we assess support for this hypothesis using direct evidence: the fitness effects of mutations in actual proteins, measured via individual or paired growth experiments. We assembled data from 8 published studies, ranging in size from 24 to 757 single-nucleotide mutations that change an amino acid. Every study has the statistical power to reveal significant effects of amino acid exchangeability, and most studies have the power to discern a binary conservative-vs-radical distinction. However, only one study suggests that transitions are significantly more conservative than transversions. In the combined set of 1239 replacements, the chance that a transition is more conservative than a transversion is 53 % (95 % confidence interval, 50 % to 56 %), compared to the null expectation of 50 %. We show that this effect is not large compared to that of most biochemical factors, and is not large enough to explain the several-fold bias observed in evolution. In short, available data have the power to verify the \""conservative transitions\"" hypothesis if true, but suggest instead that selection on proteins plays at best a minor role in the observed bias.",2015-09-28,Arlin Stoltzfus;Ryan W. Norris;,,,,True
01e3b313e78a352593be2ff64927192af66619b5,biorxiv,Viruses are a dominant driver of protein adaptation in mammals,doi.org/10.1101/029397,,,See https://www.biorxiv.org/about-biorxiv,"Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of proteins is unknown. Here, we analyze adaptation in ~1,300 virus-interacting proteins manually curated from a set of 9,900 proteins conserved across mammals. We show that viruses (i) use the more evolutionarily constrained proteins from the cellular functions they hijack and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. Our results demonstrate that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes.",2015-10-18,David Enard;Le Cai;Carina Gwenapp;Dmitri A Petrov;,,,,True
76b62badc3e093026040809913b45d437119658c,biorxiv,What’s in my pot? Real-time species identification on the MinION™,doi.org/10.1101/030742,,,See https://www.biorxiv.org/about-biorxiv,"Whole genome sequencing on next-generation instruments provides an unbiased way to identify the organisms present in complex metagenomic samples. However, the time-to-result can be protracted because of fixed-time sequencing runs and cumbersome bioinformatics workflows. This limits the utility of the approach in settings where rapid species identification is crucial, such as in the quality control of food-chain components, or in during an outbreak of an infectious disease. Here we present Whats in my Pot? (WIMP), a laboratory and analysis workflow in which, starting with an unprocessed sample, sequence data is generated and bacteria, viruses and fungi present in the sample are classified to subspecies and strain level in a quantitative manner, without prior knowledge of the sample composition, in approximately 3.5 hours. This workflow relies on the combination of Oxford Nanopore Technologies MinION sensing device with a real-time species identification bioinformatics application.",2015-11-06,Sissel Juul;Fernando Izquierdo;Adam Hurst;Xiaoguang Dai;Amber Wright;Eugene Kulesha;Roger Pettett;Daniel J Turner;,,,,False
3461d71f6890f7e5ba53bf168be3945cdb16d901,biorxiv,MERS-CoV recombination: implications about the reservoir and potential for adaptation,doi.org/10.1101/020834,,,See https://www.biorxiv.org/about-biorxiv,"Recombination is a process that unlinks neighbouring loci allowing for independent evolutionary trajectories within genomes of many organisms. If not properly accounted for, recombination can compromise many evolutionary analyses. In addition, when dealing with organisms that are not obligately sexually reproducing, recombination gives insight into the rate at which distinct genetic lineages come into contact. Since June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 1106 laboratory-confirmed infections, with 421 MERS-CoV associated deaths as of April 16, 2015. Although bats are considered as the likely ultimate source of zoonotic betacoronaviruses, dromedary camels have been consistently implicated as the source of current human infections in the Middle East. In this paper we use phylogenetic methods and simulations to show that MERS-CoV genome has likely undergone numerous recombinations recently. Recombination in MERS-CoV implies frequent co-infection with distinct lineages of MERS-CoV, probably in camels given the current understanding of MERS-CoV epidemiology.",2015-12-23,Gytis Dudas;Andrew Rambaut;,,,,True
1dd898b5ca1ae70ec0e3cad89fc87a165002a99e,biorxiv,Using heterogeneity in the population structure of U.S. swine farms to compare transmission models for porcine epidemic diarrhoea,doi.org/10.1101/017178,,,See https://www.biorxiv.org/about-biorxiv,"In 2013, U.S. swine producers were confronted with the disruptive emergence of porcine epidemic diarrhoea (PED). Movement of animals among farms is hypothesised to have played a role in the spread of PED among farms. Via this or other mechanisms, the rate of spread may also depend on the geographic density of farms and climate. To evaluate such effects on a large scale, we analyse state-level counts of outbreaks with variables describing the distribution of farm sizes and types, aggregate flows of animals among farms, and an index of climate. Our first main finding is that it is possible for a correlation analysis to be sensitive to transmission model parameters. This finding is based on a global sensitivity analysis of correlations on simulated data that included a biased and noisy observation model based on the available PED data. Our second main finding is that flows are significantly associated with the reports of PED outbreaks. This finding is based on correlations of pairwise relationships and regression modeling of total and weekly outbreak counts. These findings illustrate how variation in population structure may be employed along with observational data to improve understanding of disease spread.",2016-02-11,Eamon B O'Dea;Harry Snelson;Shweta Bansal;,,,,True
8cfb8dfc2f8b2c6e1d60ff48da02de6670694869,biorxiv,Productive infection of field strains of avian coronavirus infectious bronchitis virus in chicken peripheral blood-derived monocyte,doi.org/10.1101/041558,,,See https://www.biorxiv.org/about-biorxiv,"The avian coronavirus infectious bronchitis virus (IBV) typically infects the respiratory tract of chickens, but can also spread to other organs. However, the mechanisms of virus dissemination are presently unclear. We show that peripheral blood-derived monocytes/macrophages from chickens (chPBMC) are productively infected by clinical strains of IBV, accompanied by induction of apoptosis. Our data suggest that chPBMCs play a role in the dissemination of IBV, and may be important for viral pathogenesis.",2016-02-26,Yueting Zhang;Gary Whittaker;,,,,True
6499f5c865c3db3bdfc1e969ea940a80d547a5bb,biorxiv,Zika virus outbreak in the Americas: Is Aedes albopictus an overlooked culprit?,doi.org/10.1101/044594,,,See https://www.biorxiv.org/about-biorxiv,"Summary / AbstractCodon usage patterns of viruses reflect a series of evolutionary changes that enable viruses to shape their survival rates and fitness toward the external environment and, most importantly, their hosts. In the present study, we employed multiple codon usage analysis indices to determine genotype specific codon usage patterns of Zika virus (ZIKV) strains from the current outbreak and those reported previously. Several genotype specific and common codon usage traits were noted in ZIKV coding sequences, indicative of independent evolutionary origins from a common ancestor. The overall influence of natural selection was found to be more profound than that of mutation pressure and acting on specific set of viral genes belonging to ZIKV strains of Asian genotype from the recent outbreak. Furthermore, an interplay of codon adaptation and deoptimization have been observed in ZIKV genomes. The collective findings of codon analysis in association with the geographical data of Aedes populations in the Americas suggests that ZIKV have evolved a dynamic set of codon usage patterns in order to maintain a successful replication and transmission chain within multiple hosts and vectors.",2016-03-30,Azeem Mehmood Butt;Izza Nasrullah;Raheel Qamar;Yigang Tong;,,,,True
a59906b732bf4a489e282c3e4f499d4166c622e7,biorxiv,Evaluating performance of metagenomic characterization algorithms using in silico datasets generated with FASTQSim,doi.org/10.1101/046532,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundIn silico bacterial, viral, and human truth datasets were generated to evaluate available metagenomics algorithms. Sequenced datasets include background organisms, creating ambiguity in the true source organism for each read. Bacterial and viral datasets were created with even and staggered coverage to evaluate organism identification, read mapping, and gene identification capabilities of available algorithms. These truth datasets are provided as a resource for the development and refinement of metagenomic algorithms. Algorithm performance on these truth datasets can inform decision makers on strengths and weaknesses of available algorithms and how the results may be best leveraged for bacterial and viral organism identification and characterization.\n\nSource organisms were selected to mirror communities described in the Human Microbiome Project as well as the emerging pathogens listed by the National Institute of Allergy and Infectious Diseases. The six in silico datasets were used to evaluate the performance of six leading metagenomics algorithms: MetaScope, Kraken, LMAT, MetaPhlAn, MetaCV, and MetaPhyler.\n\nResultsAlgorithms were evaluated on runtime, true positive organisms identified to the genus and species levels, false positive organisms identified to genus and species level, read mapping, relative abundance estimation, and gene calling. No algorithm out performed the others in all categories, and the algorithm or algorithms of choice strongly depends on analysis goals. MetaPhlAn excels for bacteria and LMAT for viruses. The algorithms were ranked by overall performance using a normalized weighted sum of the above metrics, and MetaScope emerged as the overall winner, followed by Kraken and LMAT.\n\nConclusionsSimulated FASTQ datasets with well-characterized truth data about microbial community composition reveal numerous insights about the relative strengths and weaknesses of the metagenomics algorithms evaluated. The simulated datasets are available to download from the Sequence Read Archive (SRP062063).",2016-03-31,Darrell O. Ricke;Anna Shcherbina;Nelson Chiu;,,,,True
1c0b25c8e3c89243fd8797e2e964e12689bc8556,biorxiv,50-valent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques,doi.org/10.1101/053967,,,See https://www.biorxiv.org/about-biorxiv,"As the predominant etiological agent of the common cold, human rhinovirus (HRV) is the leading cause of human infectious disease. Early studies showed monovalent formalin-inactivated HRV vaccine can be protective, and virus-neutralizing antibodies (nAb) correlated with protection. However, co-circulation of many HRV types discouraged further vaccine efforts. We approached this problem straightforwardly. We tested the hypothesis that increasing virus input titers in polyvalent inactivated HRV vaccine will result in broad nAb responses. Here, we show that serum nAb against many rhinovirus types can be induced by polyvalent, inactivated HRVs plus alhydrogel (alum) adjuvant. Using formulations up to 25-valent in mice and 50-valent in rhesus macaques, HRV vaccine immunogenicity was related to sufficient quantity of input antigens, and valency was not a major factor for potency or breadth of the response. We for the first time generated a vaccine capable of inducing nAb responses to numerous and diverse HRV types.",2016-05-17,Sujin Lee;Minh Trang Nguyen;Michael Currier;Joe Jenkins;Elizabeth Strobert;Adriana Kajon;Ranjna Madan-Lala;Yury Bochkov;James Gern;Krishnendu Roy;Xiaoyan Lu;Dean Erdman;Paul Spearman;Martin Moore;,,,,True
d1b26388670660f66249b55ece2beccee4c18d1a,biorxiv,"Evidence for reassortment of highly divergent novel rotaviruses from bats in Cameroon, without evidence for human interspecies transmissions",doi.org/10.1101/054072,,,See https://www.biorxiv.org/about-biorxiv,"Bats are an important reservoir for pathogenic human respiratory and hemorrhagic viruses but only little is known about bat viruses causing gastroenteritis in humans, including rotavirus A strains (RVA). Only three RVA strains have been reported in bats in Kenya (straw-colored fruit bat) and in China (lesser horseshoe and a stoliczkas trident bat), being highly divergent from each other. To further elucidate the potential of bat RVAs to cause gastroenteritis in humans we started by investigating the genetic diversity of RVAs in fecal samples from 87 straw-colored fruit bats living in close contact with humans in Cameroon using metagenomics. Five samples contained significant numbers of RVA Illumina reads, sufficient to obtain their (near) complete genomes. A single RVA strain showed a close phylogenetic relationship with the Kenyan bat RVA strain in six gene segments, including VP7 (G25), whereas the other gene segments represented novel genotypes as ratified by the RCWG. The 4 other RVA strains were highly divergent from known strains (but very similar among each other) possessing all novel genotypes. Only the VP7 and VP4 genes showed a significant variability representing multiple novel G and P genotypes, indicating the frequent occurrence of reassortment events.\n\nComparing these bat RVA strains with currently used human RVA screening primers indicated that several of the novel VP7 and VP4 segments would not be detected in routine epidemiological screening studies. Therefore, novel VP6 based screening primers matching both human and bat RVAs were developed and used to screen samples from 25 infants with gastroenteritis living in close proximity with the studied bat population. Although RVA infections were identified in 36% of the infants, Sanger sequencing did not indicate evidence of interspecies transmissions.\n\nThis study identified multiple novel bat RVA strains, but further epidemiological studies in humans will have to assess if these viruses have the potential to cause gastroenteritis in humans.",2016-05-18,Claude K Yinda;Mark Zeller;Nadiaá Conceição-Neto;Piet Maes;Ward Deboutte;Leen Beller;Elisabeth Heylen;Stephen M Ghogomu;Marc Van Ranst;Jelle Matthijnssens;,,,,True
99dab788e984601ee4efcd1138926caf10c00dcf,biorxiv,Salt Effects on the Thermodynamics of a Frameshifting RNA Pseudoknot under Tension,doi.org/10.1101/048801,,,See https://www.biorxiv.org/about-biorxiv,"Because of the potential link between -1 programmed ribosomal frameshifting and response of a pseudoknot (PK) RNA to force, a number of single molecule pulling experiments have been performed on PKs to decipher the mechanism of programmed ribosomal frameshifting. Motivated in part by these experiments, we performed simulations using a coarse-grained model of RNA to describe the response of a PK over a range of mechanical forces (fs) and monovalent salt concentrations (Cs). The coarse-grained simulations quantitatively reproduce the multistep thermal melting observed in experiments, thus validating our model. The free energy changes obtained in simulations are in excellent agreement with experiments. By varying f and C, we calculated the phase diagram that shows a sequence of structural transitions, populating distinct intermediate states. As f and C are changed, the stem-loop tertiary interactions rupture first, followed by unfolding of the 3-end hairpin (I{rightleftharpoons}F). Finally, the 5-end hairpin unravels, producing an extended state (E{rightleftharpoons}I). A theoretical analysis of the phase boundaries shows that the critical force for rupture scales as (log Cm) with  = 1 (0.5) for E{rightleftharpoons}I (I{rightleftharpoons}F) transition. This relation is used to obtain the preferential ion-RNA interaction coefficient, which can be quantitatively measured in single-molecule experiments, as done previously for DNA hairpins. A by-product of our work is the suggestion that the frameshift efficiency is likely determined by the stability of the 5 end hairpin that the ribosome first encounters during translation.",2016-06-21,Naoto Hori;Natalia A. Denesyuk;Dave Thirumalai;,,,,True
ce621b91729031fd956d9f6045d2ae0d402de32a,biorxiv,The ATP synthase subunit β (ATP5B) is an entry factor for the hepatitis E virus,doi.org/10.1101/060434,,,See https://www.biorxiv.org/about-biorxiv,"Hepatitis E occurs sporadically and as outbreaks due to contamination of drinking water. The causative agent, hepatitis E virus (HEV) is a hepatotropic non-enveloped RNA virus, which grows poorly in vitro. Consequently, many aspects of HEV biology are poorly characterized, including its cellular receptor and entry mechanism(s). Previous studies from our laboratory have shown that heparan sulfate proteoglycans (HSPGs) act as attachment factors for the virus. In the absence of purified high titer infectious virus, we have used hepatitis E virus-like particles (HEV-LPs) expressed and purified from E. coli to identify HEV entry factor(s) on liver cells in culture. Using a pull down and mass spectrometric approach, we identified the ATP synthase subunit {beta} (ATP5B) to bind the HEV capsid protein. Its role in the entry of HEV was then validated using antibody and siRNA mediated approaches, and infectious HEV from the stools of a hepatitis E patient. Though ATP synthase is largely a mitochondrial protein, the cell surface expressed form of ATP5B is implicated in other viral infections.",2016-06-23,Zulfazal Ahmed;Prasida Holla;Imran Ahmad;Shahid Jameel;,,,,False
53442eacc3f233078507fa37b78267399e8c1e3b,biorxiv,Dysregulation of Long Non-coding RNA (lncRNA) Genes and Predicted lncRNA-protein Interactions during Zika Virus Infection,doi.org/10.1101/061788,,,See https://www.biorxiv.org/about-biorxiv,"Zika Virus (ZIKV) is a causative agent for poor pregnancy outcome and fetal developmental abnormalities, including microcephaly and eye defects. As a result, ZIKV is now a confirmed teratogen. Understanding host-pathogen interactions, specifically cellular perturbations caused by ZIKV, can provide novel therapeutic targets. In order to complete viral replication, viral pathogens control the host cellular machineries and regulate various factors, including long noncoding RNA (lncRNA) genes, at transcriptional levels. The role of lncRNA genes in the pathogenesis of ZIKV-mediated microcephaly and eye defects is currently unknown. To gain additional insights, we focused on profiling the differentially expressed lncRNA genes during ZIKV infection in mammalian cells. For this study, we employed a contemporary clinical Zika viral isolate, PRVABC59, of Asian genotype. We utilized an unbiased RNA sequencing approach to profile the lncRNA transcriptome in ZIKV infected Vero cells. We identified a total of 121 lncRNA genes that are differentially regulated at 48 hours post-infection. The majority of these genes are independently validated by reverse-transcription qPCR. A notable observation was that the lncRNAs, MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) and NEAT1 (Nuclear Paraspeckle Assembly Transcript 1), are down-regulated upon Zika viral infection. MALAT1 and NEAT1 are known as nuclear localized RNAs that regulate gene expression and cell proliferation. Protein-lncRNA interaction maps revealed that MALAT1 and NEAT1 share common interacting partners and form a larger network comprising of 71 cellular factors. ZIKV-mediated dysregulation of these two regulatory lncRNAs can alter the expression of respective target genes and associated biological functions, an important one being cell division. In conclusion, this investigation is the first to provide insight into the biological connection of lncRNAs and ZIKV which can be further explored for developing antiviral therapy and understanding fetal developmental processes.",2016-07-01,Arunachalam Ramaiah;Deisy Contreras;Vineela Gangalapudi;Masumi Sameer Padhye;Jie Tang;Vaithilingaraja Arumugaswami;,,,,True
3b73c8abb7528c958cec0bae1890828af007b599,biorxiv,How domain growth is implemented determines the long term behaviour of a cell population through its effect on spatial correlations.,doi.org/10.1101/041509,,,See https://www.biorxiv.org/about-biorxiv,"Domain growth plays an important role in many biological systems, and so the inclusion of domain growth in models of these biological systems is important to understanding how these biological systems function. In this work we present methods to include the effects of domain growth on the evolution of spatial correlations in a continuum approximation of a lattice-based model of cell motility and proliferation. We show that, depending on the way in which domain growth is implemented, different steady-state densities are predicted for an agent population. Furthermore, we demonstrate that the way in which domain growth is implemented can result in the evolution of the agent density depending on the size of the domain. Continuum approximations that ignore spatial correlations cannot capture these behaviours, while those that account for spatial correlations do. These results will be of interest to researchers in developmental biology, as they suggest that the nature of domain growth can determine the characteristics of cell populations.",2016-07-10,Robert JH Ross;Ruth E Baker;Christian A Yates;,,,,True
97339c9d365437d54ea33be1a1b634d35f460208,biorxiv,Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modeling Study,doi.org/10.1101/053421,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundThe ongoing yellow fever (YF) epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa in July-August 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidating the conditions under which dose fractionation would reduce transmission.\n\nMethodsWe estimate the effective reproductive number for YF in Angola using disease natural history and case report data. With simple mathematical models of YF transmission, we calculate the infection attack rate (IAR, the proportion of population infected over the course of an epidemic) under varying levels of transmissibility and five-fold fractional-dose vaccine efficacy for two vaccination scenarios: (i) random vaccination in a hypothetical population that is completely susceptible; (ii) the Kinshasa vaccination campaign in July-August 2016 with different age cutoff for fractional-dose vaccines.\n\nFindingsWe estimate the effective reproductive number early in the Angola outbreak was between 5{middle dot}2 and 7{middle dot}1. If vaccine action is all-or-nothing (i.e. a proportion VE of vaccinees receives complete and the remainder receive no protection), n-fold fractionation can dramatically reduce IAR as long as efficacy VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (i.e. the susceptibility of each vaccinee is reduced by a factor that is equal to the vaccine efficacy VE). The age cutoff for fractional-dose vaccines chosen by the WHO for the Kinshasa vaccination campaign (namely, 2 years) provides the largest reduction in IAR if the efficacy of five-fold fractional-dose vaccines exceeds 20%.\n\nInterpretationDose fractionation is a very effective strategy for reducing infection attack rate that would be robust with a large margin for error in case fractional-dose VE is lower than expected.\n\nFundingNIH-MIDAS, HMRF-Hong Kong",2016-07-25,Joseph T. Wu;Corey M. Peak;Gabriel M. Leung;Marc Lipsitch;,,,,True
c04e10858012bdd666d50c0d69c3d1e7224ccbea,biorxiv,Design: An assay based on single-polypeptide-chain heterodimeric A2AR/D2R and non-oligomerized fusions for in vivo analysis of their allosteric receptor-receptor interactions,doi.org/10.1101/065250,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundThe adenosine A2A receptor (A2AR) heteromerizes with the dopamine D2 receptor (D2R). In order to explore their functional interaction, we engineered previously stable single-polypeptide-chain (sc) A2AR/D2LR: whether the molecular entity of the striatal A2AR/D2R antagonism, i.e., scA2AR/D2Rs are just A2AR/D2R with the antagonism, remains unresolved.\n\nNew MethodTo further clarify the heteromerization through the scA2AR/D2LR, we here designed supramolecularly  exclusive monomers and dimers, using the C{varepsilon}2 domain of IgE-Fc or apoproteins of the bacterial light-harvesting antenna complex.\n\nResultsA concept of the recptor protein assembly regulation, i.e., the selective monomer/non-obligate dimer formation was obtained. Although none of these new fusions were constructed or tested, we could aim at obtaining heterodimer-specific agents, using the scA2AR/D2R. Whether the resulting designs were explained feasibly and rationally was addressed. The structure and function of the non-obligate dimer were here discussed through scA2AR/D2R, focusing on the procedure of the membrane protein design and methods for transient protein-protein interactions.\n\nSummary and OutlookGiven that upon being expressed and allosteric regulation occurs regardless of specific signal to non-specific noise (S/N) ratio, the supramolecular designs, allowing us to express selectively monomer/non-obligate dimer of class A GPCR, are experimentally testable and will be used to confirm in vivo that such low S/N ratio interaction between A2AR and D2LR functions in the dopamine neurotransmission in the striatum.\n\nAbbreviations",2016-07-26,Toshio KAMIYA;Takashi Masuko;Dasiel Oscar Borroto-Escuela;Haruo Okado;Hiroyasu Nakata;,,,,True
ffbf8ea9948d73572fd052a74afa01b19e6758a3,biorxiv,Planning horizon affects prophylactic decision-making and epidemic dynamics,doi.org/10.1101/069013,,,See https://www.biorxiv.org/about-biorxiv,"Human behavior can change the spread of infectious disease. There is limited understanding of how the time in the future over which individuals make a behavioral decision, their planning horizon, affects epidemic dynamics. We developed an agent-based model (along with an ODE analog) to explore the decision-making of self-interested individuals on adopting prophylactic behavior. The decision-making process incorporates prophylaxis efficacy and disease prevalence with individuals' payoffs and planning horizon. Our results show that for short and long planning horizons individuals do not consider engaging in prophylactic behavior. In contrast, individuals adopt prophylactic behavior when considering intermediate planning horizons. Such adoption, however, is not always monotonically associated with the prevalence of the disease, depending on the perceived protection efficacy and the disease parameters. Adoption of prophylactic behavior reduces the peak size while prolonging the epidemic and potentially generates secondary waves of infection. These effects can be made stronger by increasing the behavioral decision frequency or distorting an individuals perceived risk of infection.",2016-08-12,Luis G. Nardin;Craig R. Miller;Benjamin J. Ridenhour;Stephen M. Krone;Paul Joyce;Bert O. Baumgaertner;,,,,True
fd3fc2c49f5cc27e4262261d0c9045911d65cb6e,biorxiv,XRN1 is a Species-Specific Virus Restriction Factor in Yeasts,doi.org/10.1101/069799,,,See https://www.biorxiv.org/about-biorxiv,"In eukaryotes, the degradation of cellular mRNAs is accomplished by Xrn1p and the cytoplasmic exosome. Because viral RNAs often lack canonical caps or poly-A tails, they can also be vulnerable to degradation by these host exonucleases. Yeast lack sophisticated mechanisms of innate and adaptive immunity, but do use RNA degradation as an antiviral defense mechanism. One model is that the RNA of yeast viruses is subject to degradation simply as a side effect of the intrinsic exonuclease activity of proteins involved in RNA metabolism. Contrary to this model, we find a highly refined, species-specific relationship between Xrn1p and the \""L-A\"" totiviruses of different Saccharomyces yeast species. We show that the gene XRN1 has evolved rapidly under positive natural selection in Saccharomyces yeast, resulting in high levels of Xrn1p protein sequence divergence from one yeast species to the next. We also show that these sequence differences translate to differential interactions with the L-A virus, where Xrn1p from S. cerevisiae is most efficient at controlling the L-A virus that chronically infects S. cerevisiae, and Xrn1p from S. kudriavzevii is most efficient at controlling the L-A-like virus that we have discovered within S. kudriavzevii. All Xrn1p orthologs are equivalent in their interaction with another virus-like parasite, the Ty1 retrotransposon. Thus, the activity of Xrn1p against totiviruses is not simply an incidental consequence of the enzymatic activity of Xrn1p, but rather Xrn1p co-evolves with totiviruses to maintain its potent antiviral activity and limit viral propagation in Saccharomyces yeasts. Consistent with this, we demonstrated that Xrn1p physically interacts with the Gag protein encoded by the L-A virus, suggesting a host-virus interaction that is more complicated than just Xrn1p-mediated nucleolytic digestion of viral RNAs.",2016-08-16,Paul A Rowley;Brandon Ho;Sarah Bushong;Arlen Johnson;Sara L Sawyer;,,,,True
44a440cc1c135c938d2216ea672f8ef4f9c01296,biorxiv,Genome-wide prediction of microRNAs in Zika virus genomes reveals possible interactions with human genes involved in the nervous system development,doi.org/10.1101/070656,,,See https://www.biorxiv.org/about-biorxiv,"Zika virus (ZIKV) is a member of the family Flaviviridae. In 2015, ZIKV triggered a large epidemic in Brazil and spread across Latin America. In November of that year, the Brazilian Ministry of Health reported a 20-fold increase in cases of neonatal microcephaly, which corresponds geographically and temporally to the ZIKV outbreak. ZIKV was isolated from the brain tissue of a fetus diagnosed with microcephaly, and recent studies in mice models revealed that ZIKV infection may cause brain defects by influencing brain cell developments. Unfortunately, the mechanisms by which ZIKV alters neurophysiological development remain unknown. MicroRNAs (miRNAs) are small noncoding RNAs that regulate post-transcriptional gene expression by translational repression. In order to gain insight into the possible role of ZIKV-mediated miRNA signaling dysfunction in brain-tissue development, we computationally predicted new miRNAs encoded by the ZIKV genome and their effective hybridization with transcripts from human genes previously shown to be involved in microcephalia. The results of these studies suggest a possible role of these miRNAs on the expression of human genes associated with this disease. Besides, a new ZIKV miRNA was predicted in the 3stem loop (3 SL) of the 3untranslated region (3UTR) of the ZIKV genome, suggesting the role of the 3UTR of flaviviruses as a source of miRNAs.",2016-08-21,Juan Cristina;Natalia Echeverria;Fabiana Gambaro;Alvaro Fajardo;Pilar Moreno;,,,,True
f68d813dfab153c1b0850ac63d0562003972290d,biorxiv,Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barre syndrome: systematic review,doi.org/10.1101/073098,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundThe World Health Organization stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain-Barre syndrome and of microcephaly and other congenital brain abnormalities, based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were: to update and re-assess the evidence for causality through a rapid and systematic review about links between Zika virus infection and a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and b) Guillain-Barre syndrome in any population; and to describe the process and outcomes of an expert assessment of the evidence about causality.\n\nMethods and findingsThe study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in 10 dimensions; temporality, biological plausibility, strength of association, alternative explanations, cessation, dose-response, animal experiments, analogy, specificity and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction and quality assessment, and summarised evidence descriptively. Third, a multidisciplinary panel of experts assessed the review findings and reached consensus on causality. We found 1091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of 10 causality dimensions (all except dose-response relationship and specificity) we found that more than half the relevant studies supported a causal association with Zika virus infection. For Guillain-Barre syndrome, we included 36 items, of which more than half the relevant studies supported a causal association in seven of ten dimensions (all except dose-response relationship, specificity and animal experimental evidence). Articles identified non-systematically from May 30-July 29, 2016 strengthened the review findings. The expert panel concluded that: a) the most likely explanation of available evidence from outbreaks of Zika virus infection and clusters of microcephaly is that Zika virus infection during pregnancy is a cause of congenital brain abnormalities including 61 microcephaly; and b) the most likely explanation of available evidence from outbreaks of Zika virus infection and Guillain-Barre syndrome is that Zika virus infection is a trigger of Guillain-Barre syndrome. The expert panel recognised that Zika virus alone may not be sufficient to cause either congenital brain abnormalities or Guillain-Barre syndrome but agreed that the evidence was sufficient to recommend increased public health measures. Weaknesses are the limited assessment of the role of dengue virus and other possible co-factors, the small number of comparative epidemiological studies, and the difficulty in keeping the review up to date with the pace of publication of new research.\n\nConclusionsRapid and systematic reviews with frequent updating and open dissemination are now needed, both for appraisal of the evidence about Zika virus infection and for the next public health threats that will emerge. This rapid systematic review found sufficient evidence to say that Zika virus is a cause of congenital abnormalities and is a trigger of Guillain-Barre situation.",2016-09-06,Fabienne Krauer;Maurane Riesen;Ludovic Reveiz;Olufemi T Oladapo;Ruth Martinez-Vega;Teegwende V Porgo;Anina Haefliger;Nathalie J Broutet;Nicola Low;WHO Zika Causality Working Group;,,,,False
8f4b98da50277e6c9516aef0227f5cca9af6b5e8,biorxiv,Identification of quercetin from fruits to immediately fight Zika,doi.org/10.1101/074559,,,See https://www.biorxiv.org/about-biorxiv,"Zika virus is spread mainly by the bite of an infected mosquito, which can be passed from a pregnant woman to her fetus, thus leading to birth defects including more than microcephaly. It has been recently estimated that one-third of the world population will be infected by Zika in the near future, but unfortunately so far there is no vaccine or medicine for Zika. In particular, the special concern on the vaccine treatment to Zika and Dengue arising from antibody-dependent enhancement strongly emphasizes the key role of its NS2B-NS3 protease (NS2B-NS3pro) as a target for anti-Zika drug discovery/design due to its absolutely-essential role in viral replication.\n\nIn response to the current global health emergency triggered by the Zika outbreak, we successfully obtained several active forms of Zika NS2B-NS3pro and further attempted to discover its inhibitors from eatable plants and traditional herbal medicines to immediately fight Zika. Here, for the first time, we discovered that quercetin, a flavonoid extensively existing in many fruits and vegetables, effectively inhibits Zika NS2B-NS3pro. We further quantify its inhibitory activity with IC50 of 26.0 {+/-} 0.1 {micro}M; and Ki of 23.0 {+/-} 1.3 {micro}M. As quercetin has been extensively found in fruits, vegetables, leaves and grains, our discovery would benefit the public to immediately fight Zika.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=165 SRC=\""FIGDIR/small/074559_ufig1.gif\"" ALT=\""Figure 1\"">\nView larger version (55K):\norg.highwire.dtl.DTLVardef@18e716dorg.highwire.dtl.DTLVardef@b8d5f6org.highwire.dtl.DTLVardef@e7206aorg.highwire.dtl.DTLVardef@11cf2_HPS_FORMAT_FIGEXP  M_FIG C_FIG",2016-09-11,Amrita Roy;Liangzhong Lim;Jianxing Song;,,,,True
f9b108c052ded463773a9838a8157ac7d5ba6d1a,biorxiv,Unique properties of Zika NS2B-NS3pro complexes as decoded by experiments and MD simulations,doi.org/10.1101/078113,,,See https://www.biorxiv.org/about-biorxiv,"Zika virus can be passed from a pregnant woman to her fetus, thus leading to birth defects including more than microcephaly. It has been recently estimated that one-third of the world population will be infected by Zika, but unfortunately no vaccine or medicine is available so far. Zika NS2B-NS3pro is essential for its replication and thus represents an attractive target for drug discovery/design. Here we characterized conformation, catalysis, inhibition and dynamics of linked and unlinked Zika NS2B-NS3pro complexes by both experiments and MD simulations. The results unveil the unique properties of Zika NS2B-NS3pro which are very different from Dengue one. Particularly, CD and NMR studies indicate that unlike Dengue, the C-terminal region of Zika NS2B with a significant sequence variation is highly disordered in the open conformation. Indeed, MD simulations reveal that up to 100 ns, the Dengue NS2B C-terminus constantly has close contacts with its NS3pro domain. By a sharp contrast, the Zika NS2B C-terminus loses the contacts with its NS3pro domain after 10 ns, further forming a short {beta}-sheet characteristic of the closed conformation at 30 ns. Furthermore, we found that a small molecule, previously identified as an active site inhibitor for other flaviviral NS2B-NS3pro, inhibited Zika NS2B-NS3pro potently in an allosteric manner. Our study provides the first insight into the dynamics of Zika NS2B-NS3pro and further deciphers that it is susceptible to allosteric inhibition, which thus bears critical implications for the future development of therapeutic allosteric inhibitors.",2016-09-28,Amrita Roy;Liangzhong Lim;Shagun Srivastava;Jianxing Song;,,,,True
8e2d6b823b09dc0f9440827572ebf3a438f13bdb,biorxiv,Comparative analysis of variation and selection in the HCV genome,doi.org/10.1101/078584,,,See https://www.biorxiv.org/about-biorxiv,"Genotype 1 of the hepatitis C virus (HCV) is the most prevalent of the variants of this virus. Its two main subtypes, HCV-1a and HCV-1b, are associated to differences in epidemic features and risk groups, despite sharing similar features in most biological properties. We have analyzed the impact of positive selection on the evolution of these variants using complete genome coding regions, and compared the levels of genetic variability and the distribution of positively selected sites. We have also compared the distributions of positively selected and conserved sites considering different factors such as RNA secondary structure, the presence of different epitopes (antibody, CD4 and CD8), and secondary protein structure. Less than 10% of the genome was found to be under positive selection, and purifying selection was the main evolutionary force in both subtypes. We found differences in the number of positively selected sites between subtypes in several genes (Core, HVR2 in E2, P7, helicase in NS3 and NS4a). Heterozygosity values in positively selected sites and the rate of non-synonymous substitutions were significantly higher in subtype HCV-1b. Logistic regression analyses revealed that similar selective forces act at the genome level in both subtypes: RNA secondary structure and CD4 T-cell epitopes are associated with conservation, while CD8 T-cell epitopes are associated with positive selection in both subtypes. These results indicate that similar selective constraints are acting along HCV-1a and HCV-1b genomes, despite some differences in the distribution of positively selected sites at independent genes.",2016-09-30,Juan Angel Patino Galindo;Fernando Gonzalez Candelas;,,,,False
5b27a16123f46b5aaeda3171d22e075dcbd36ee6,biorxiv,Identification of a Zika NS2B-NS3pro pocket susceptible to allosteric inhibition by small molecules including qucertin rich in edible plants,doi.org/10.1101/078543,,,See https://www.biorxiv.org/about-biorxiv,"It has been recently estimated that one-third of the world population will be infected by Zika virus, but unfortunately so far there is no vaccine or medicine available. In particular, the special concern on the vaccine treatment to Zika and Dengue arising from antibody-dependent enhancement strongly emphasizes the irreplaceable role of its NS2B-NS3 protease (NS2B-NS3pro) as a target for anti-Zika drug discovery/design due to its absolutely-essential role in viral replication. Very recently we identified two small molecules inhibit Zika NS2B-NS3pro in non-competitive mode, with Ki values of 0.57 and 2.02 {micro}M respective for p-Nitrophenyl-p-guanidino benzoate and qucertin. Here, by molecular docking, we show that although one is designed compound while another is a natural product, both molecules bind to the same pocket on the back of the substrate-binding pocket of Zika NS2B-NS3pro. As the two inhibitors fundamentally differ from cn-716, the only known peptidomimetic boronic acid inhibitor in both structure scaffolds and inhibitory modes, our discovery might open up a new avenue for the future development of allosteric inhibitors, which is highly demanded to achieve therapeutic inhibition of flaviviral NS2B-NS3pro complexes. Furthermore, as qucertin is abundant in many vegetables and fruits such caper, lovage, tea and red onion, our results should benefit the public to immediately fight Zika virus.",2016-10-01,Liangzhong Lim;Amrita Roy;Jianxing Song;,,,,True
28b107243576723248ad4053261000311a22f134,biorxiv,"Genetic,transcriptome, proteomic and epidemiological evidence for blood brain barrier disruption and polymicrobial brain invasion as determinant factors in Alzheimers disease.",doi.org/10.1101/080333,,,See https://www.biorxiv.org/about-biorxiv,"Multiple pathogens have been detected in Alzheimers disease (AD) brains. A bioinformatics approach was used to assess relationships between pathogens and AD genes (GWAS), the AD hippocampal transcriptome and plaque or tangle proteins. Host/pathogen interactomes (C.albicans, C.Neoformans, Bornavirus, B.Burgdorferri, cytomegalovirus, Ebola virus, HSV-1, HERV-W, HIV-1, Epstein-Barr, hepatitis C, influenza, C.Pneumoniae, P.Gingivalis, H.Pylori, T.Gondii, T.Cruzi) significantly overlap with misregulated AD hippocampal genes, with plaque and tangle proteins and, except Bornavirus, Ebola and HERV-W, with AD genes. Upregulated AD hippocampal genes match those upregulated by multiple bacteria, viruses, fungi or protozoa in immunocompetent blood cells. AD genes are enriched in bone marrow and immune locations and in GWAS datasets reflecting pathogen diversity, suggesting selection for pathogen resistance. The age of AD patients implies resistance to infections afflicting the younger. APOE4 protects against malaria and hepatitis C, and immune/inflammatory gain of function applies to APOE4, CR1, TREM2 and presenilin variants. 30/78 AD genes are expressed in the blood brain barrier (BBB), which is disrupted by AD risk factors (ageing, alcohol, aluminium, concussion, cerebral hypoperfusion, diabetes, homocysteine, hypercholesterolaemia, hypertension, obesity, pesticides, pollution, physical inactivity, sleep disruption and smoking). The BBB and AD benefit from statins, NSAIDs, oestrogen, melatonin and the Mediterranean diet. Polymicrobial involvement is supported by the upregulation of pathogen sensors/defenders (bacterial, fungal, viral) in the AD brain, blood or CSF. Cerebral pathogen invasion permitted by BBB inadequacy, activating a hyper-efficient immune/inflammatory system, betaamyloid and other antimicrobial defence may be responsible for AD which may respond to antibiotic, antifungal or antiviral therapy.",2016-10-12,Chris J Carter;,,,,True
5570cb9ff2905fda60cfd6e94f3c32774b765265,biorxiv,"The genome of the crustacean Parhyale hawaiensis: a model for animal development, regeneration, immunity and lignocellulose digestion",doi.org/10.1101/065789,,,See https://www.biorxiv.org/about-biorxiv,"The amphipod crustacean Parhyale hawaiensis is a blossoming model system for studies of developmental mechanisms and more recently regeneration. We have sequenced the genome allowing annotation of all key signaling pathways, transcription factors, and non-coding RNAs that will enhance ongoing functional studies. Parhyale is a member of the Malacostraca clade, which includes crustacean food crop species. We analysed the immunity related genes of Parhyale as an important comparative system for these species, where immunity related aquaculture problems have increased as farming has intensified. We also find that Parhyale and other species within Multicrustacea contain the enzyme sets necessary to perform lignocellulose digestion (\""wood eating\""), suggesting this ability may predate the diversification of this lineage. Our data provide an essential resource for further development of Parhyale as an experimental model. The first malacostracan genome will underpin ongoing comparative work in food crop species and research investigating lignocellulose as an energy source.",2016-10-13,"Kao, D.; Lai, A. G.; Stamataki, E.; Rosic, S.; Konstantinides, N.; Jarvis, E.; Di Donfrancesco, A.; Pouchkina-Stantcheva, N.; Semon, M.; Grillo, M.; Bruce, H.; Kumar, S.; Siwanowicz, I.; Le, A.; Lemire, A.; Eisen, M.; Extavour, C.; Browne, W.; Wolff, C.; Averof, M.; Patel, N. H.; Sarkies, P.; Pavlopoulos, A.; Aboobaker, A.",,,,True
e6fe63419fe399f9c77513c1c11a043db006a2f3,biorxiv,Accurate prediction of human essential genes using only nucleotide composition and association information,doi.org/10.1101/084129,,,See https://www.biorxiv.org/about-biorxiv,"Three groups recently identified essential genes in human cancer cell lines using wet experiments, and these genes are of high values. Herein, we improved the widely used Z curve method by creating a {lambda}-interval Z curve, which considered interval association information. With this method and recursive feature elimination technology, a computational model was developed to predict human gene essentiality. The 5-fold cross-validation test based on our benchmark dataset obtained an area under the receiver operating characteristic curve (AUC) of 0.8814. For the rigorous jackknife test, the AUC score was 0.8854. These results demonstrated that the essentiality of human genes could be reliably reflected by only sequence information. However, previous classifiers in three eukaryotes can gave satisfactory prediction only combining sequence with other features. It is also demonstrated that although the information contributed by interval association is less than adjacent nucleotides, this information can still play an independent role. Integrating the interval information into adjacent ones can significantly improve our classifiers prediction capacity. We re-predicted the benchmark negative dataset by Pheg server (https://cefg.uestc.edu.cn/Pheg), and 118 genes were additionally predicted as essential. Among them, 21 were found to be homologues in mouse essential genes, indicating that at least a part of the 118 genes were indeed essential, however previous experiments overlooked them. As the first available server, Pheg could predict essentiality for anonymous gene sequences of human. It is also hoped the {lambda}-interval Z curve method could be effectively extended to classification issues of other DNA elements.",2016-10-28,"Guo, F.-B.; Dong, C.; Hua, H.-L.; Liu, S.; Luo, H.; Zhang, H.-W.; Jin, Y.-T.; Zhang, K.-Y.",,,,True
dff716159738acd6bd53b4be12af45358a58752e,biorxiv,MYCOPLASMA FAUCIUM AND BREAST CANCER,doi.org/10.1101/089128,,,See https://www.biorxiv.org/about-biorxiv,"Viruses and bacteria are the cause of a large number of different human diseases. It is believed that some of them may even contribute to the development of cancer. The present work is dedicated to the identification of mycoplasmas in patients with breast cancer. Mycoplasmas may participate in the development of several human diseases including chronic fatigue syndrome, acquired immunodeficiency syndrome, atypical pneumonia, etc. Moreover, there is a reason to believe that mycoplasma can participate in the development of cancer, leukemia and lymphoma.\n\nDNA samples from blood, saliva and tumor tissues of the Oncology Institute of Moldova patients diagnosed with breast cancer were analyzed. Mycoplasma testing was performed using nested PCR method. For Mycoplasma spp. detection, we used primers from the region of the 16S-23S RNA genes. The identification of Mycoplasma faucium, Mycoplasma salivarium and Mycoplasma orale was performed by nested PCR with primers for RNA polymerase beta subunit gene corresponding to mycoplasma.\n\nM.faucium and M.salivarius was found in saliva at about 100%, and M.orale at a frequency of about 50%. Only M.faucium was found with the frequency of about 60% in the tissue of the patients. Moreover, a fairly high rate of detection of mycoplasma is observed both in the cases when primers for RNA polymerase gene and primers for 16S-23S RNA were used.\n\nWe found M.faucium in tumor tissues of patients diagnosed with breast cancer. It is known that mycoplasmas are able to stimulate the synthesis of certain cytokines, which act as mitogenes on the cell. We assume that M.faucium can stimulate the mitogenes synthesis in breast tissues (e.g., cytokines) which, in turn, stimulate cell division and thus participate in the initiation of breast cancer.",2016-11-22,"Mitin, V.; Tumanova, L.; Botnariuc, N.",,,,True
8c900409a679dc1f16ef13c73500cbb53605b683,biorxiv,Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses,doi.org/10.1101/090936,,,See https://www.biorxiv.org/about-biorxiv,"The severity and outcome of respiratory viral infections is partially determined by the cellular response mounted by infected lung epithelial cells. Disease prevention and treatment is dependent on our understanding of the shared and unique responses elicited by diverse viruses, yet few studies compare host responses to different viruses while controlling other experimental parameters. We compared changes in gene expression of murine lung epithelial cells infected individually by three respiratory viruses causing mild (rhinovirus, RV1B), moderate (coronavirus, MHV-1), and severe (influenza A virus, PR8) disease in mice. RV1B infection caused numerous gene expression changes, but the differential effect peaked at 12 hours post-infection. PR8 altered an intermediate number of genes whose expression continued to change through 24 hours. MHV-1 had comparatively few effects on host gene expression. The viruses elicited highly overlapping responses in antiviral genes, though MHV-1 induced a lower type I interferon response than the other two viruses. Signature genes were identified for each virus and included host defense genes for PR8, tissue remodeling genes for RV1B, and transcription factors for MHV-1. Our comparative approach identified universal and specific transcriptional signatures of virus infection that can be used to discover mechanisms of pathogenesis in the respiratory tract.",2016-12-02,"Van Leuven, J. T.; Ridenhour, B. J.; Miller, C. R.; Miura, T. A.",,,,True
6aa2716c00d89f4b760a9167b15d6203303ae6b9,biorxiv,Vitrification after multiple rounds of sample application and blotting improves particle density on cryo-electron microscopy grids.,doi.org/10.1101/094623,,,See https://www.biorxiv.org/about-biorxiv,"Single particle cryo-electron microscopy (cryoEM) is becoming widely adopted as a tool for structural characterization of biomolecules at near-atomic resolution. Vitrification of the sample to obtain a dense distribution of particles within a single field of view remains a major bottleneck for the success of such experiments. Here, we describe a simple and cost-effective method to increase the density of frozen-hydrated particles on grids with holey carbon support films. It relies on performing multiple rounds of sample application and blotting prior to plunge freezing in liquid ethane. We show that this approach is generally applicable and significantly increases particle density for a range of samples, such as small protein complexes, viruses and filamentous assemblies. The method is versatile, easy to implement, minimizes sample requirements and can enable characterization of samples that would otherwise resist structural studies using single particle cryoEM.",2016-12-15,"Snijder, J.; Borst, A. J.; Dosey, A.; Walls, A. C.; Burrell, A.; Reddy, V. S.; Kollman, J. M.; Veesler, D.",,,,True
9b5f5119bbfbded3245acc37859cefde967458e7,biorxiv,Containing Emerging Epidemics: a Quantitative Comparison of Quarantine and Symptom Monitoring,doi.org/10.1101/072652,,,See https://www.biorxiv.org/about-biorxiv,"Strategies for containing an emerging infectious disease outbreak must be non-pharmaceutical when drugs or vaccines for the pathogen do not yet exist or are unavailable. The success of these non-pharmaceutical strategies will depend not only on the effectiveness of quarantine or other isolation measures but also on the epidemiological characteristics of the infection. However, there is currently no systematic framework to assess the relationship between different containment strategies and the natural history and epidemiological dynamics of the pathogen. Here, we compare the effectiveness of quarantine and symptom monitoring, implemented via contact tracing, in controlling epidemics using an agent-based branching model. We examine the relationship between epidemic containment and the disease dynamics of symptoms and infectiousness for seven case study diseases with diverse natural histories including Ebola, Influenza A, and Severe Acute Respiratory Syndrome (SARS). We show that the comparative effectiveness of symptom monitoring and quarantine depends critically on the natural history of the infectious disease, its inherent transmissibility, and the intervention feasibility in the particular healthcare setting. The benefit of quarantine over symptom monitoring is generally maximized for fast-course diseases, but we show the conditions under which symptom monitoring alone can control certain outbreaks. This quantitative framework can guide policy-makers on how best to use non-pharmaceutical interventions to contain emerging outbreaks and prioritize research during an outbreak of a novel pathogen.\n\nSIGNIFICANCEQuarantine and symptom monitoring of contacts with suspected exposure to an infectious disease are key interventions for the control of emerging epidemics; however, there does not yet exist a quantitative framework for comparing the control performance of each. Here, we use a mathematical model of seven case study diseases to show how the choice of intervention is influenced by the natural history of the infectious disease, its inherent transmissibility, and the intervention feasibility in the particular healthcare setting. We use this information to identify the most important characteristics of the disease and setting that need to be characterized for an emerging pathogen in order to make an informed decision between quarantine and symptom monitoring.",2016-12-22,"Peak, C. M.; Childs, L. M.; Grad, Y. H.; Buckee, C. O.",,,,True
8eb99586e9103599ab2f58cc33ca94cd0b60ae53,biorxiv,Epidemiological and ecological modelling reveal diversity in microbial population structures from a cross-sectional community swabbing study,doi.org/10.1101/099069,,,See https://www.biorxiv.org/about-biorxiv,"Respiratory tract infections (RTI) are responsible for over 4 million deaths per year worldwide with pathobiont carriage a required precursor to infection. Through a cross-sectional community-based nasal self-swabbing study we sought to determine carriage epidemiology for respiratory pathogens amongst bacteria (Streptococcus pneumoniae, Haemophilus influenza, Moraxella catarrhalis, Staphylococcus aureus, Pseudomonas aeruginosa and Neisseria meningitidis) and viruses (RSV, Influenza viruses A and B, Rhinovirus/Enterovirus, Coronavirus, Parainfluenza viruses 1-3 and Adenovirus (ADV)). Carriage of bacterial and viral species was shown to vary with participant age, recent RTI and the presence of other species. The spatial structure of microbial respiratory communities was less nested (more disordered) in the young (0-4 years) and those with recent RTI. Species frequency distributions were flatter than random expectation in young individuals (X2 = 20.42, p = 0.002), indicating spatial clumping of species consistent with facilitative relationships amongst them. Deviations from a neutral model of ecological niches were observed for samples collected in the summer and from older individuals (those aged 5-17, 18-64 and [&ge;]65 years) but not in samples collected from winter, younger individuals (those aged 0-4 years), individuals with recent RTI and individuals without recent RTI, demonstrating the importance of both neutral and niche processes in respiratory community assembly. The application of epidemiological methods and ecological theory to sets of respiratory tract samples has yielded novel insights into the factors that drive microbial community composition, such as seasonality and age, as well as species patterns and interactions within the nose.",2017-01-09,"Coughtrie, A. L.; Morris, D. E.; Anderson, R.; Begum, N.; Cleary, D. W.; Faust, S. N.; Jefferies, J. M.; Kraaijeveld, A. R.; Moore, M. V.; Mullee, M. A.; Roderick, P. J.; Tuck, A.; Whittaker, R. N.; Yuen, H. M.; Doncaster, C. P.; Clarke, S. C.",,,,True
e0fd364797eb02a280e25e2649dfe6d6c0d33e05,biorxiv,Spike-based phylogenetically defined clades within the Alphacoronavirus 1 species,doi.org/10.1101/101774,,,See https://www.biorxiv.org/about-biorxiv,"Taxonomic classification for the Coronaviridae can be challenging, due to the wide host tropism and highly variable genome of the viruses in this Family. Within the Alphacoronavirus genus, there is a single species Alphacoronavirus 1 that encompasses several biologically distinct viruses of distinct animal species. Here, we carried out phylogenetic analysis of members of the Alphacoronavirus genus, focusing on the viral spike gene, which is a primary driver of viral tropism and pathogenesis. We identify two distinct clades (A and B) within the Alphacoronavirus 1 species. Alphacoronavirus 1 clade A encompasses serotype I FCoV and CCoV, and Alphacoronavirus 1 clade B, encompasses serotype II FCoV and CCoV and TGEV-like viruses. We propose this clade designation, along with the newly proposed Alphacoronavirus 2 species, as an improved way to classify the diverse Alphacoronavirus genus.",2017-01-19,"Whittaker, G. R.; Andre, N. M.; Millet, J. K.",,,,True
3737964303e971a5a418bc42a411aa1d0a797696,biorxiv,The immunomodulatory CEA cell adhesion molecule 6 (CEACAM6/CD66c) is a candidate receptor for the influenza A virus,doi.org/10.1101/104026,,,See https://www.biorxiv.org/about-biorxiv,"To establish a productive infection in host cells, viruses often use one or multiple host membrane glycoprotein as their receptors. For Influenza A virus (IAV) such a glycoprotein receptor has not been described, to date. Here we show that IAV is using the host membrane glycoprotein CD66c as a receptor for entry into human epithelial lung cells. Neuraminidase (NA), a viral spike protein binds to CD66c on the cell surface during IAV entry into the host cells. Lung cells overexpressing CD66c showed an increase in virus binding and subsequent entry into the cell. Upon comparison, CD66c demonstrated higher binding capacity than other membrane glycoproteins (EGFR and DC-SIGN) reported earlier to facilitate IAV entry into host cells. siRNA mediated knockdown of CD66c from lung cells inhibited virus binding on cell surface and entry into cells. Blocking CD66c by antibody on the cell surface resulted in decreased virus entry. We found CD66c is a specific glycoprotein receptor for influenza A virus that did not affect entry of non-IAV RNA virus (Hepatitis C virus). Finally, IAV pre-incubated with recombinant CD66c protein when administered intranasally in mice showed decreased cytopathic effects in mice lungs. This publication is the first to report CD66c (CEACAM6) as a glycoprotein receptor for Influenza A virus.\n\nSignificance StatementCells are enclosed by a semipermeable membrane that allows selective exchange of biomolecules between cells and their surroundings. A set of specialized proteins in this semipermeable membrane, work like gatekeepers to the cell and regulate entry of these biomolecules. One class of such surface proteins is termed as receptors. Viruses bind to one or more of these receptors and manipulate gatekeepers for their own successful entry into host-cells. A membrane protein that influenza A virus (Flu virus) uses for entry into the cells was not discovered till date. This study reports for the first time, a receptor for influenza A virus, that was sought after by researchers for decades. The viral receptor is a promising target that can be used to inhibit virus entry into host cells.",2017-01-30,"Rahman, S. K.; Ansari, M. A.; Gaur, P.; Ahmad, I.; Chakravarty, C.; Verma, D. K.; Chhibber, S.; Nehal, N.; Sellathanby, S.; Wirth, D.; Waris, G.; Lal, S. K.",,,,False
95754ec84bdee0637765a5ee34983a5f6cc86eed,biorxiv,PGC-1α coordinates with Bcl-2 to control cell cycle in U251 cells through reducing ROS,doi.org/10.1101/111567,,,See https://www.biorxiv.org/about-biorxiv,"B-cell lymphoma 2 (Bcl-2) has a dual function, acting both as an oncogene and an anti-tumor gene. It is well known that Bcl-2 exerts its tumor promoting function through the mitochondrial pathway. However, the mechanism by which Bcl-2 suppresses tumor formation is not well understood. We have previously shown that Bcl-2 inhibits cell cycle progression from the G0/G1 to the S phase after serum starvation, and that quiescent Bcl-2 expressing cells maintained a significant lower level of mitochondrial reactive oxygen species (ROS) than the control cells. Based on the fact that ROS mediate cell cycle progression, and are controlled by peroxisome proliferator-activated receptor-{gamma} co-activator 1 (PGC-1), a key molecule induced by prolonged starvation and involved in mitochondrial metabolism, we hypothesized that PGC-1 might be related with the cell cycle function of Bcl-2. Here, we showed that PGC-1 was upregulated upon Bcl-2 overexpression and downregulated following Bcl-2 knockdown during serum starvation. Knockdown of PGC-1 activated Bcl-2 expression. Taken together, our results suggest that after serum depletion, PGC-la might coordinate with Bcl-2 to reduce ROS, which in turn delay cell cycle progression.\n\nSummary statementPGC-1 coordinate with Bcl-2 delay cell cycle progression to reduce ROS after serum depletion in human glioma U251 cells.",2017-02-24,"Yao, K.; Fu, X.; Du, X.; Li, Y.; Han, B.; Chen, Z.; Yang, S.; Wei, R.; Zhou, J.; Cui, Q.",,,,True
b4fc44eabb1f640124fff98990c85dc5c9984aee,biorxiv,The translational landscape of Zika virus during infection of mammalian and insect cells,doi.org/10.1101/112904,,,See https://www.biorxiv.org/about-biorxiv,"Zika virus is a single-stranded, positive-sense RNA virus of the family Flaviviridae, which has recently undergone a rapid expansion among humans in the Western Hemisphere. Here, we report a high-resolution map of ribosomal occupancy of the Zika virus genome during infection of mammalian and insect cells, obtained by ribosome profiling. In contrast to some other flaviviruses such as West Nile, we find no evidence for substantial frameshift-induced ribosomal drop-off during translation of the viral polyprotein, indicating that Zika virus must use alternative mechanisms to downregulate levels of catalytically active viral polymerase. We also show that high levels of ribosome-protected fragments map in-frame to two previously overlooked upstream open reading frames (uORFs) initiating at CUG and UUG codons, with likely consequences for the efficiency of polyprotein expression. Curiously, in African isolates of Zika virus, the two uORFs are fused in-frame into a single uORF. A parallel RNA-Seq analysis reveals the 5' end position of the subgenomic flavivirus RNA in mammalian and insect cells. Together, these provide the first analysis of flavivirus gene expression by ribosome profiling.\n\nAuthor SummaryRecent Zika virus outbreaks have been associated with congenital diseases and neurological complications. An enhanced understanding of the molecular biology of this pathogen may contribute towards the development of improved treatment and control methods. We present a single-codon resolution analysis of Zika virus translation in mammalian and mosquito cells using ribosome profiling. The analysis revealed two hitherto uncharacterized uORFs in the 5' leader of Zika virus Brazilian isolate PE243, both of which are occupied by ribosomes during infection. In contrast, these two uORFs are fused into a single uORF in African isolates. This observation provides a new avenue for further investigations into potential factors involved in the emergence of Zika virus from a rarely detected pathogen into a major epidemic.",2017-03-02,"Irigoyen, N.; Dinan, A. M.; Meredith, L. W.; Goodfellow, I. G.; Brierley, I.; Firth, A. E.",,,,True
d91120d80916351170b34715ea4ab141f02c51fb,biorxiv,Prophage genomics reveals patterns in phage genome organization and replication,doi.org/10.1101/114819,,,See https://www.biorxiv.org/about-biorxiv,"Temperate phage genomes are highly variable mosaic collections of genes that infect a bacterial host, integrate into the hosts genome or replicate as low copy number plasmids, and are regulated to switch from the lysogenic to lytic cycles to generate new virions and escape their host. Genomes from most Bacterial phyla contain at least one or more prophages. We updated our PhiSpy algorithm to improve detection of prophages and to provide a web-based framework for PhiSpy. We have used this algorithm to identify 36,488 prophage regions from 11,941 bacterial genomes, including almost 600 prophages with no known homology to any proteins. Transfer RNA genes were abundant in the prophages, many of which alleviate the limits of translation efficiency due to host codon bias and presumably enable phages to surpass the normal capacity of the hosts translation machinery. We identified integrase genes in 15,765 prophages (43% of the prophages). The integrase was routinely located at either end of the integrated phage genome, and was used to orient and align prophage genomes to reveal their underlying organization. The conserved genome alignments of phages recapitulate early, middle, and late gene order in transcriptional control of phage genes, and demonstrate that gene order, presumably selected by transcription timing and/or coordination among functional modules has been stably conserved throughout phage evolution.",2017-03-07,"Kang, H. S.; McNair, K.; Cuevas, D.; Bailey, B.; Segall, A.; Edwards, R. A.",,,,True
0cb9c296684ca5e71462d825cab2827854a01544,biorxiv,P53 is not necessary for DUX4 pathology,doi.org/10.1101/118315,,,See https://www.biorxiv.org/about-biorxiv,"AbstractsFSHD is a genetically dominant myopathy caused by mutations that cause expression of the normally silent DUX4 gene. This transcription factor has been shown to interfere with myogenesis when misexpressed at very low levels in myoblasts, and to cause cell death when overexpressed at high levels. A previous report using adeno-associated virus to deliver high levels of DUX4 to mouse skeletal muscle demonstrated severe pathology that was suppressed on a p53 knockout background, implying that DUX4 acted through the p53 pathway. Here, we investigate the p53-dependence of DUX4 using both in vitro cellular and the transgenic iDUX4[2.7] mouse models. We find that inhibiting p53 has no effect on the cytoxicity of DUX4 in vitro. When crossed onto the p53 null background, we find no suppression of the male-specific lethality or skin phenotypes of the DUX4 transgene, and find that primary myoblasts from this mouse are still killed by DUX4 expression. These data challenge the notion that the p53 pathway is central to the pathogenicity of DUX4.\n\nSummary StatementDUX4 is thought to mediate cytopathology through p53. Here, DUX4 is shown to kill primary myoblasts and promote pathological phenotypes in the iDUX4[2.7] mouse model on the p53-null background, calling into question this notion.",2017-03-19,"Bosnakovski, D.; Toso, E. A.; Recht, O. O.; Cucak, A.; Jain, A. K.; Barton, M. C.; Kyba, M.",,,,True
d418cdee18b07a0adfb553d43b4a08f7736fa9f3,biorxiv,Metagenomic Sequencing Detects Respiratory Pathogens in Hematopoietic Cellular Transplant Patients,doi.org/10.1101/102798,,,See https://www.biorxiv.org/about-biorxiv,"RATIONALECurrent microbiologic diagnostics often fail to identify the etiology of lower respiratory tract infections (LRTI) in hematopoietic cellular transplant recipients (HCT), which precludes the implementation of targeted therapies.\n\nOBJECTIVESTo address the need for improved LRTI diagnostics, we evaluated the utility of metagenomic next generation sequencing (mNGS) of bronchoalveolar lavage (BAL) to detect microbial pathogens in HCT patients with acute respiratory illnesses.\n\nMETHODSWe enrolled 22 post-HCT adults ages 19-69 years with acute respiratory illnesses who underwent BAL at the University of Michigan between January 2012 and May 2013. mNGS was performed on BAL fluid to detect microbes and simultaneously assess the host transcriptional response. Results were compared against conventional microbiologic assays.\n\nMEASUREMENTS & MAIN RESULTSmNGS demonstrated 100% sensitivity for detecting respiratory microbes (human metapneumovirus, respiratory syncytial virus, Stenotrophomonas maltophilia, human herpesvirus 6 and cytomegalovirus) when compared to standard testing. Previously unrecognized LRTI pathogens were identified in six patients for whom standard testing was negative (human coronavirus 229E, human rhinovirus A, Corynebacterium propinquum and Streptococcus mitis); findings were confirmed by independent PCR and 16S rRNA sequencing. Relative to patients without infection, patients with infection had increased expression of immunity related genes (p=0.022) and significantly lower diversity of their respiratory microbiome (p=0.017).\n\nCONCLUSIONSCompared to conventional diagnostics, mNGS enhanced detection of pathogens in BAL fluid from HCT patients. Furthermore, our results suggest that combining unbiased microbial pathogen detection with assessment of host gene biomarkers of immune response may hold promise for enhancing the diagnosis of post-HCT respiratory infections.",2017-04-10,"Langelier, C.; Zinter, M. S.; Kalantar, K.; Yank, G. A.; Christenson, S.; Odonovan, B.; White, C.; Wilson, M. R.; Sapru, A.; Dvorak, C. C.; Miller, S.; Chiu, C. Y.; DeRisi, J. L.",,,,True
45f184e736c4a857bc0e3df0d55962f743c1493a,biorxiv,Similar ratios of introns to intergenic sequence across animal genomes,doi.org/10.1101/068627,,,See https://www.biorxiv.org/about-biorxiv,"One central goal of genome biology is to understand how the usage of the genome differs between organisms. Our knowledge of genome composition, needed for downstream inferences, is critically dependent on gene annotations, yet problems associated with gene annotation and assembly errors are usually ignored in comparative genomics. Here we analyze the genomes of 68 species across all animal groups and some single-cell eukaryotes for general trends in genome usage and composition, taking into account problems of gene annotation. We show that, regardless of genome size, essentially all animals have comparable amounts of introns and intergenic sequence, with nearly all deviations dominated by increased intergenic sequence. Genomes of model organisms have ratios much closer to 1:1, suggesting that the majority of published genomes of non-model organisms are underannotated and consequently omit substantial numbers of genes, with likely negative impact on evolutionary interpretations. Finally, our results also indicate that most animals transcribe half or more of their genomes arguing against differences in genome usage between animal groups, and also suggesting that the transcribed portion is more dependent on genome size than previously thought.\n\nAuthors SummaryWithin our anthropocentric genomic framework, many analyses tends to try to define humans, mammals, or vertebrates relative to the so-called \""lower\"" animals. This implicitly posits that vertebrates are complex organisms with large genomes and invertebrates are simple organisms with small genomes. This has the problem that genome size is therefore presumed to correlate with complexity and ignores any unknown complexity of vast numbers of invertebrate groups, many with large genomes. Animals vary widely in genome size, by almost three orders of magnitude, but when sequencing new animal genomes preference is given to those with smaller genomes for reasons of cost. In trying to understand how genomes are used in general, there is an added layer of complication from quality of the assembly and annotation. We have examined genome usage across a wide range of animals and have described ways to account for errors of low-quality annotations. We also show that the genomes of invertebrates and vertebrates are not so different, and that when large-genome invertebrates are added, genome size alone appears to be defining the fraction of the genome that is genes.",2017-05-09,"Francis, W. R.; Worheide, G.",,,,True
88e3b43319399c339186c02c44d369228c35eef4,biorxiv,An anti-cancer binary system activated by bacteriophage HK022 Integrase,doi.org/10.1101/147736,,,See https://www.biorxiv.org/about-biorxiv,"Cancer gene therapy is a great promising tool for cancer therapeutics due to the specific targeting based on the cancerous gene expression background. Binary systems based on site-specific recombination are one of the most effective potential approaches for cancer gene therapy. In these systems, a cancer specific promoter expresses a site-specific recombinase/integrase that in turn controls the expression of a toxin gene. In the current study, we have developed a new HK022 bacteriophage Integrase (Int) based binary system activating a Diphtheria toxin (DTA) gene expression specifically in cancer cells. We have demonstrated the efficiency, and the high specificity of the system in vitro in cell cultures and in vivo in a lung cancer mouse model. Strikingly, different apoptotic and anti-apoptotic factors demonstrated a remarkable efficacy killing capability of the Int-based binary system compared to the conventional hTERT-DTA mono system in the LLC-Kat lung cancer mice model; we observed that the active hTERT promoter down regulation by the transcription factors Mad-1 is the cornerstone of this phenomenon. The new Int-based binary system offers advantages over already known counterparts and may therefore be developed into a safer and efficient cancer treatment technology.",2017-06-12,"Elias, A.; Spector, I.; Gritsenko, N.; Zilberstein, Y.; Gorovits, R.; Prag, G.; Kolot, M.",,,,True
90e28ff462882ca7a9329beb879f73c2e99430e4,biorxiv,Evolutionary proteomics uncovers ciliary signaling components,doi.org/10.1101/153437,,,See https://www.biorxiv.org/about-biorxiv,"Cilia are organelles specialized for movement and signaling. To infer when during animal evolution signaling pathways became associated with cilia, we characterized the proteomes of cilia from three organisms: sea urchins, sea anemones and choanoflagellates. From these ciliomes, we identified 437 high confidence ciliary candidate proteins conserved in mammals, including known regulators of Hh, GPCR and TRP channel signaling. The phylogenetic profiles of their ciliary association indicate that the Hh and GPCR pathways were linked to cilia before the origin of bilateria and TRP channels before the origin of animals. We demonstrated that some of the candidates not previously implicated in ciliary biology localized to cilia and further investigated ENKUR, a TRP channel-interacting protein that we identified in the cilia of all three organisms. In animals, ENKUR is expressed by cells with motile cilia, ENKUR localizes to cilia in diverse organisms and, in both Xenopus laevis and mice, ENKUR is required for patterning the left/right axis. Moreover, mutation of ENKUR causes situs inversus in humans. Thus, proteomic profiling of cilia from diverse eukaryotes defines a conserved ciliary proteome, reveals ancient connections to Hh, GPCR and TRP channel signaling, and uncovers a novel ciliary protein that controls vertebrate development and human disease.",2017-06-22,"Sigg, M. A.; Menchen, T.; Johnson, J.; Lee, C.; Choksi, S. P.; Garcia, G.; Busengdal, H.; Dougherty, G.; Pennekamp, P.; Werner, C.; Rentzsch, F.; Krogan, N.; Wallingford, J. B.; Omran, H.; Reiter, J. F.",,,,True
dd69db23811a5046c30cf8462961cd960fd129d2,biorxiv,Mapping the drivers of within-host pathogen evolution using massive data sets,doi.org/10.1101/155242,,,See https://www.biorxiv.org/about-biorxiv,"Differences among hosts, resulting from genetic variation in the immune system or heterogeneity in drug treatment, can impact within-host pathogen evolution. Identifying such interactions can potentially be achieved through genetic association studies. However, extensive and correlated genetic population structure in hosts and pathogens presents a substantial risk of confounding analyses. Moreover, the multiple testing burden of interaction scanning can potentially limit power. To address these problems, we have developed a Bayesian approach for detecting host influences on pathogen evolution that makes use of vast existing data sets of pathogen diversity to improve power and control for stratification. The approach models key processes, including recombination and selection, and identifies regions of the pathogen genome affected by host factors. Using simulations and empirical analysis of drug-induced selection on the HIV-1 genome we demonstrate the power of the method to recover known associations and show greatly improved precision-recall characteristics compared to other approaches. We build a high-resolution map of HLA-induced selection in the HIV-1 genome, identifying novel epitope-allele combinations.",2017-06-25,"Palmer, D. S.; Turner, I.; Fidler, S.; Frater, J.; Goulder, P.; Goedhals, D.; Huang, K.-H. G.; Oxenius, A.; Phillips, R.; Shapiro, R.; van Vuuren, C.; McLean, A. R.; McVean, G.",,,,False
b5161b031c7f720562e94735a018d1c3c8be3ae5,biorxiv,Quantifying the Risk and Cost of Active Monitoring for Infectious Diseases,doi.org/10.1101/156497,,,See https://www.biorxiv.org/about-biorxiv,"During outbreaks of deadly emerging pathogens (e.g., Ebola, MERS-CoV) and bioterror threats (e.g., smallpox), actively monitoring potentially infected individuals aims to limit disease transmission and morbidity. Guidance issued by CDC on active monitoring was a cornerstone of its response to the West Africa Ebola outbreak. There are limited data on how to balance the costs and performance of this important public health activity. We present a framework that estimates the risks and costs of specific durations of active monitoring for pathogens of significant public health concern. We analyze data from New York Citys Ebola active monitoring program over a 16-month period in 2014-2016. For monitored individuals, we identified unique durations of active monitoring that minimize expected costs for those at \""low (but not zero) risk\"" and \""some or high risk\"": 21 and 31 days, respectively. Extending our analysis to smallpox and MERS-CoV, we found that the optimal length of active monitoring relative to the median incubation period was reduced compared to Ebola due to less variable incubation periods. Active monitoring can save lives but is expensive. Resources can be most effectively allocated by using exposure-risk categories to modify the duration or intensity of active monitoring.",2017-06-28,"Reich, N. G.; Lessler, J.; Varma, J. K.; Vora, N. M.",,,,True
9d16ecb93103967effb08d7ba6120a2d7ebe4b52,biorxiv,Self-assembled Star-shaped Chiroplasmonic Gold Nanoparticles for Ultrasensitive Chiro-immunosensor of Viruses,doi.org/10.1101/162412,,,See https://www.biorxiv.org/about-biorxiv,"Near field optics and optical tunneling light-matter interaction in the superstructure of chiral nanostructures and semiconductor quantum dots exhibit strong optical rotation activity that may open a new window for chiral-based bioanalytes detection. Herein we report an ultrasensitive, chiro-immunosensor using superstructure of chiral gold nanohybrids (CAu NPs) and quantum dots (QDs). Self-assembling techniques were employed to create asymmetric plasmonic chiral nanostructures for extending the spectral range of circular dichroism (CD) response for obtaining superior plasmonic resonant coupling with the QDs excitonic state; this may help to achieve lower the limit of detection (LOD) values. As a result, the designed probe exhibited avian influenza A (H5N1) viral concentration at picomolar level, a significant improvement in sensitivity in comparison to a non-assembled CAu NPs based chiroassay. The practicability of the proposed sensing system was successfully demonstrated on several virus cultures including, avian influenza A (H4N6) virus, fowl adenovirus and coronavirus in blood samples. The results of our study highlights that exciton-plasmon interaction changes chirality and the self-assembled nanostructures are an efficient strategy for enhancing the sensitivity of plasmonic nanosensors.",2017-07-12,"Ahmed, S. R.; Nagy, E.; Neethirajan, S.",,,,False
5d9e490190986584d799e2828c6fd9679e5ae159,biorxiv,The IFN response in bat cells consists of canonical and non-canonical ISGs with unique temporal expression kinetics,doi.org/10.1101/167999,,,See https://www.biorxiv.org/about-biorxiv,"Bats are reservoirs for a number of highly pathogenic zoonotic viruses, yet they remain relatively asymptomatic during infection. Whether this viral resistance is due to a unique innate immune system is unknown. An evolutionarily conserved feature of vertebrate antiviral immunity is the interferon (IFN) response, which triggers cellular defenses through interferon-stimulated gene (ISG) expression. While bats encode an intact IFN system, global ISG expression patterns in bat cells are not well characterized. Here, we used RNA-Seq to assess the transcriptional response to IFN in cells derived from the bat Pteropus alecto (black flying fox). We show induction of more than 100 transcripts, most of which are canonical ISGs observed in other species. Kinetic gene profiling revealed that P. alecto ISGs fall into two unique temporal subclusters with similar early induction kinetics but distinct late-phase declines. In contrast to bat ISGs, human ISGs generally remained elevated for longer periods following IFN treatment, suggesting host-based differences in gene regulatory mechanisms. Notably, we also identified a small group of non-canonical bat ISGs, including an enzymatically active RNASEL that plays a role in controlling viral infection. These studies provide insight into the innate immune response of an important viral reservoir and lay a foundation for studies into the immunological features that may underlie unique virus-host relationship in bats.\n\nSignificance StatementBats are considered unique in their ability to resist disease caused by viruses that are often pathogenic in humans. While the nature of this viral resistance is unknown, genomic data suggest bat innate immune systems may be specialized in controlling these disease-causing viruses. A critical cell intrinsic antiviral defense system in vertebrates is the interferon response, which suppresses viral infection through induction of hundreds of interferon-stimulated genes (ISGs). In this study, we report the repertoire of ISGs and several unique features of ISG induction kinetics in bat cells. We also characterize induction and antiviral activity of bat RNASEL, which is induced by IFN in bat, but not human cells. These studies lay the foundation for discovery of potentially new antiviral mechanisms in bats, which may spur research into development of therapies to combat viral infection.",2017-07-24,"De La Cruz-Rivera, P. C.; Kanchwala, M.; Liang, H.; Kumar, A.; Wang, L.-F.; Xing, C.; Schoggins, J.",,,,True
0b4b4e5bb8d0d5167eec1e203b5dad283bd364a5,biorxiv,Doubling healthy lifespan using drug synergies,doi.org/10.1101/153205,,,See https://www.biorxiv.org/about-biorxiv,"Pharmacological interventions that target human ageing would extend individual healthspan and result in dramatic economic benefits to rapidly ageing societies worldwide. For such interventions to be contemplated they need to comprise drugs that are efficacious when given to adults and for which extensive human safety data are available. Here we show that dramatic lifespan extension can be achieved in C.elegans by targeting multiple, evolutionarily conserved ageing pathways using drugs that are already in human use. By targeting multiple synergistic ageing pathways, we are able to slow ageing rate, double lifespan and improves healthspan while minimize developmental and fitness trade-offs. Moreover, we established that there is no synergistic benefit in a daf-2 or daf-7 background, implying the involvement of the TGF{beta} and IGF pathways in this synergy. Employing lipidomics and transcriptomics analysis we found lipid metabolism to be affected resulting in increased monounsaturated fatty acids (MUFA) and decrease membrane peroxidation index. Our best drug combination showed a conserved lifespan extension in fruit flies. To the best of our knowledge, this is the largest lifespan effect ever reported for any adult-onset drug treatment in C. elegans. This drug-repurposing approach, using drugs already approved for humans to target multiple conserved aging pathways simultaneously, could lead to interventions that prevent age-related diseases and overall frailty in a rapidly ageing population.",2017-08-01,"Dessale, T.; Batchu, K. C.; Barardo, D.; Ng, L. F.; Lam, V. Y. M.; Xiao, L.; Wenk, M. R.; Tolwinski, N. S.; Gruber, J.",,,,True
656ef218f7dcea5555a59cdc29d0f9ec8d5c2a82,biorxiv,MERS-CoV NSP16 necessary for IFN resistance and viral pathogenesis,doi.org/10.1101/173286,,,See https://www.biorxiv.org/about-biorxiv,"Coronaviruses encode a mix of highly conserved and novel genes as well as genetic elements necessary for infection and pathogenesis, raising the possibility for common targets for attenuation and therapeutic design. In this study, we focus on the highly conserved nonstructural protein (NSP) 16, a viral 2O methyl-transferase (MTase) that encodes critical functions in immune modulation and infection. Using reverse genetics, we disrupted a key motif in the conserved KDKE motif of MERS NSP16 (D130A) and evaluated the effect on viral infection and pathogenesis. While the absence of 2O MTase activity had only marginal impact on propagation and replication in Vero cells, the MERS dNSP16 mutant demonstrated significant attenuation relative to control both in primary human airway cultures and in vivo. Further examination indicated the MERS dNSP16 mutant had a type I IFN based attenuation and was partially restored in the absence of IFIT molecules. Importantly, the robust attenuation permitted use of MERS dNSP16 as a live attenuated vaccine platform protecting from challenge with a mouse adapted MERS-CoV strain. These studies demonstrate the importance of the conserved 2O MTase activity for CoV pathogenesis and highlight NSP16 as a conserved universal target for rapid live attenuated vaccine design in an expanding CoV outbreak setting.\n\nSignificanceCoronavirus emergence in both human and livestock represents a significant threat to global public health, as evidenced by the sudden emergence of SARS-CoV, MERS-CoV, PEDV and swine delta coronavirus in the 21st century. These studies describe an approach that effectively targets the highly conserved 2O methyl-transferase activity of coronaviruses for attenuation. With clear understanding of the IFN/IFIT based mechanism, NSP16 mutants provide a suitable target for a live attenuated vaccine platform as well as therapeutic development for both current and future emergent CoV strains. Importantly, other approaches targeting other conserved pan-coronavirus functions have not yet proven effective against MERS-CoV, illustrating the broad applicability of targeting viral 2O MTase function across coronaviruses.",2017-08-08,"Menachery, V. D.; Gralinski, L. E.; Mitchell, H. D.; Dinnon, K. H.; Leist, S. R.; Yount, B. L.; Graham, R. L.; McAnarney, E. T.; Stratton, K. G.; Cockrell, A. S.; Debbink, K.; Sims, A. C.; Waters, K. M.; Baric, R. S.",,,,True
7a51b191fd6575831585eee67a0ac67f209d8fcb,biorxiv,Nuclease escape elements protect messenger RNA against cleavage by multiple viral endonucleases,doi.org/10.1101/155457,,,See https://www.biorxiv.org/about-biorxiv,"During lytic Kaposis sarcoma-associated herpesvirus (KSHV) infection, the viral endonu-clease SOX promotes widespread degradation of cytoplasmic messenger RNA (mRNA). However, select mRNAs, including the transcript encoding interleukin-6 (IL-6), escape SOX-induced cleavage. IL-6 escape is mediated through a 3 UTR RNA regulatory element that overrides the SOX targeting mechanism. Here, we reveal that this protective RNA element functions to broadly restrict cleavage by a range of homologous and non-homologous viral endonucleases. However, it does not impede cleavage by cellular endonucleases. The IL-6 protective sequence may be representative of a larger class of nuclease escape elements, as we identified a similar protective element in the GADD45B mRNA. The IL-6 and GADD45B-derived elements display similarities in their sequence, putative structure, and several associated RNA binding proteins. However, the overall composition of their ribonucleoprotein complexes appears distinct, leading to differences in the breadth of nucleases restricted. These findings highlight how RNA elements can selectively control transcript abundance in the background of widespread virus-induced mRNA degradation.\n\nAUTHOR SUMMARYThe ability of viruses to control the host gene expression environment is crucial to promote viral infection. Many viruses express factors that reduce host gene expression through widespread mRNA decay. However, some mRNAs escape this fate, like the transcript encoding the immunoregulatory cytokine IL-6 during KSHV infection. IL-6 escape relies on an RNA regulatory element located in its 3UTR and involves the recruitment of a protective protein complex. Here, we show that this escape extends beyond KSHV to a variety of related and unrelated viral endonucleases. However, the IL-6 element does not protect against cellular endonucleases, revealing for the first time a virus-specific nuclease escape element. We identified a related escape element in the GADD45B mRNA, which displays several similarities with the IL-6 element. However, these elements assemble a largely distinct complex of proteins, leading to differences in the breadth of their protective capacity. Collectively, these findings reveal how a putative new class of RNA elements function to control RNA fate in the background of widespread mRNA degradation by viral endonucleases.",2017-08-11,"Muller, M.; Glaunsinger, B. A.",,,,True
f126b7f9c8ba02a0f872b51cf95d08086e0bd4ac,biorxiv,Proofreading-deficient coronaviruses adapt over long-term passage for increased fidelity and fitness without reversion of exoribonuclease-inactivating mutations,doi.org/10.1101/175562,,,See https://www.biorxiv.org/about-biorxiv,"The coronavirus (CoV) RNA genome is the largest among single-stranded positive sense RNA viruses. CoVs encode a proofreading 3'[-&gt;]5'exoribonuclease within nonstructural protein 14 (nsp14-ExoN) that is responsible for CoV high-fidelity replication. Alanine substitution of ExoN catalytic residues [ExoN(-)] in SARS-CoV and murine hepatitis virus (MHV) disrupts ExoN activity, yielding viable mutant viruses with defective replication, up to 20-fold decreased fidelity, and increased susceptibility to nucleoside analogs. To test the stability of the ExoN(-) genotype and phenotype, we passaged MHV-ExoN(-) 250 times in cultured cells (P250), in parallel with WT-MHV. Compared to MHV-ExoN(-) P3, MHV-ExoN(-) P250 demonstrated enhanced replication, reduced susceptibility to nucleoside analogs, and increased competitive fitness. However, passage did not select for complete or partial reversion at the ExoN-inactivating mutations. We identified novel amino acid changes within the RNA-dependent RNA polymerase (nsp12-RdRp) and nsp14 of MHV-ExoN(-) P250 that partially account for the observed changes in replication, susceptibility to nucleoside analogs, and competitive fitness observed in the passaged virus population, indicating that additional determinants can compensate for the activities of nsp14-ExoN. Our results suggest that while selection favors restoration of replication fidelity in ExoN(-) CoVs, there may be a significant barrier to ExoN(-) reversion. These results also support the hypothesis that high-fidelity replication is linked to CoV fitness and identify additional candidate proteins that may regulate CoV replication fidelity.\n\nIMPORTANCEUnique among RNA viruses, CoVs encode a proofreading exoribonuclease (ExoN) in nsp14 that mediates high-fidelity RNA genome replication. Proofreading-deficient CoVs with disrupted ExoN activity [ExoN(-)] are either non-viable or have significant defects in replication, RNA synthesis, fidelity, fitness, and virulence. In this study, we show that ExoN(-) murine hepatitis virus can adapt over long-term passage for increased replication and fitness without reverting the ExoN-inactivating mutations. Passage-adapted ExoN(-) mutants also demonstrate increasing resistance to nucleoside analogs that is only partially explained by secondary mutations in nsp12 and nsp14. These data suggest that enhanced resistance to nucleoside analogs is mediated by the interplay of multiple replicase proteins and support the proposed link between CoV fidelity and fitness.",2017-08-11,"Graepel, K.; Lu, X.; Case, J. B.; Sexton, N. R.; Smith, E. C.; Denison, M. R.",,,,True
f122e125c2cd3580b1a38e27c780b99f671fd78f,biorxiv,An Amino Acid Motif In HLA-DRB1 Distinguishes Patients With Uveitis In Juvenile Idiopathic Arthritis,doi.org/10.1101/140954,,,See https://www.biorxiv.org/about-biorxiv,"ObjectivesUveitis is a visually-debilitating disorder that affects up to 30% of children with the most common forms of juvenile idiopathic arthritis (JIA). The disease mechanisms predisposing only a subgroup of children to uveitis are unknown. To identify genetic susceptibility loci for uveitis in JIA, we conducted a genome-wide association study totalling 522 JIA cases.\n\nMethodsTwo cohorts of JIA patients with ophthalmological follow-up were separately genotyped and then imputed using a genome-wide imputation reference panel, and an HLA-specific reference panel used for imputing amino acids and HLA types in the major histocompatibility complex (MHC). After imputation, we performed genome-wide and MHC-specific analyses. We used a reverse immunology approach to model antigen presentation at 13 common HLA-DRB1 allotypes.\n\nResultsWe identified the amino acid serine at position 11 (serine-11) in HLA-DRB1 as associated to increased risk of uveitis (OR = 2.60, p = 5.43 x 10-10). We found the serine-11 signal to be specific to females (pfemales = 7.61 x 10-10, pmales = 0.18). Serine-11 resides in the YST-motif in the peptide binding groove of the HLA-DRB1 protein; all three amino acids are in perfect linkage disequilibrium and show identical association to disease. Quantitative prediction of binding affinity revealed that discernable peptide-binding preferences distinguish HLA-DRB1 allotypes with the YST-motif.\n\nConclusionOur findings highlight a genetically distinct, sexually-dimorphic feature of JIA-uveitis compared to JIA without uveitis in HLA-DRB1. The association indicates the potential involvement for antigen presentation by HLA-DRB1 in the development of uveitis in JIA.",2017-08-14,"Haasnoot, A. J. W.; Schilham, M. W.; Kamphuis, S. S. M.; Hissink Muller, P. C. E.; Heiligenhaus, A.; Foll, D.; Ophoff, R. A.; Minden, K.; Radstake, T. R. D. J.; Den Hollander, A. I.; Reinards, T. H. C. M.; Hiddingh, S.; Schalij-Delfos, N.; Hoppenreijs, E. P. A. H.; van Rossum, M. A. J.; Wouters, C.; Saurenmann, R. K.; Wulffraat, N.; ICON-JIA Study Group,  ; ten Cate, R.; de Boer, J. H.; Pulit, S. L.; Kuiper, J. J. W.",,,,True
fbbc51bcd0de87e312bfda1939821d13561d0ba3,biorxiv,Myeloablation-associated deletion of ORF4 in a human coronavirus 229E infection,doi.org/10.1101/113423,,,See https://www.biorxiv.org/about-biorxiv,"We describe metagenomic next-generation sequencing (mNGS) of a human coronavirus 229E from a patient with AML and persistent upper respiratory symptoms, who underwent hematopoietic cell transplantation (HCT). mNGS revealed a 548-nucleotide deletion, which comprised the near entirety of the ORF4 gene, and no minor allele variants were detected to suggest a mixed infection. As part of her pre-HCT conditioning regimen, the patient received myeloablative treatment with cyclophosphamide and 12 Gy total body irradiation. Iterative sequencing and RT-PCR confirmation of 4 respiratory samples over the 4-week peritransplant period revealed that the pre-conditioning strain contained an intact ORF4 gene, while the deletion strain appeared just after conditioning and persisted over a 2.5-week period. This sequence represents one of the largest genomic deletions detected in a human RNA virus and describes large-scale viral mutation associated with myeloablation for HCT.",2017-08-26,"Greninger, A.; Pepper, G.; Shean, R. C.; Cent, A.; Palileo, I.; Kuypers, J. M.; Schiffer, J. T.; Jerome, K. R.",,,,False
3d690de86ca6e200f4f9cac61b004e47ad753aae,biorxiv,Mouse hepatitis virus nsp14 exoribonuclease activity is required for resistance to innate immunity,doi.org/10.1101/182196,,,See https://www.biorxiv.org/about-biorxiv,"ABSTRACTCoronaviruses (CoV) are positive-sense RNA viruses that infect numerous mammalian and avian species and are capable of causing severe and lethal disease in humans. CoVs encode several innate immune antagonists that interact with the host innate immune response to facilitate efficient viral replication. CoV non-structural protein 14 (nsp14) encodes 3'-to-5' exoribonuclease activity (ExoN), which performs a proofreading function and is required for high-fidelity replication. Outside of the order Nidovirales, arenaviruses are the only RNA viruses that encode an ExoN, which functions to degrade dsRNA replication intermediates. In this study, we tested the hypothesis that CoV ExoN may also function to antagonize the innate immune response. We demonstrate that viruses lacking ExoN activity [ExoN(-)] are sensitive to cellular pretreatment with interferon beta (IFN-{beta}) in a dose-dependent manner. In addition, ExoN(-) virus replication was attenuated in wild-type bone marrow-derived macrophages (BMMs) and partially restored in interferon alpha/beta receptor deficient (IFNAR-/-) BMMs. ExoN(-) virus replication did not result in IFN-{beta} gene expression, and in the presence of an IFN-{beta}-mediated antiviral state, ExoN(-) viral RNA levels were not substantially reduced relative to untreated. However, ExoN(-) virus generated from IFN-{beta} pretreated cells had reduced specific infectivity and decreased relative fitness, suggesting that ExoN(-) virus generated during an antiviral state is less viable to establish a subsequent infection. Overall, our data suggest MHV ExoN activity is required for resistance to the innate immune response and antiviral mechanisms affecting the viral RNA sequence and/or an RNA modification act on viruses lacking ExoN activity.",2017-08-29,"Case, J. B.; Li, Y.; Elliott, R.; Lu, X.; Graepel, K. W.; Sexton, N. R.; Smith, E. C.; Weiss, S. R.; Denison, M. R.",,,,True
7116ddab89281e7641fb659019c90ee3715f5039,biorxiv,The impact of persistent bacterial bronchitis on the pulmonary microbiome of children,doi.org/10.1101/181982,,,See https://www.biorxiv.org/about-biorxiv,"AbstractPersistent bacterial bronchitis is a leading cause of chronic wet cough in young children. This study aimed to characterise the respiratory bacterial microbiota of healthy children and to assess the impact of the changes associated with the development of persistent bacterial bronchitis.\n\nBlind, protected brushings were obtained from 20 healthy controls and 24 children with persistent bacterial bronchitis, with an additional directed sample obtained from persistent bacterial bronchitis patients. DNA was extracted, quantified using a 16S rRNA gene quantitative PCR assay prior to microbial community analysis by 16S rRNA gene sequencing.\n\nNo significant difference in bacterial diversity or community composition (R2 = 0.01, P = 0.36) was observed between paired blind and non-blind brushes, showing that blind brushings are a valid means of accessing the airway microbiota. This has important implications for collecting lower respiratory samples from healthy children. A significant decrease in bacterial diversity (P < 0.001) and change in community composition (R2 = 0.08, P = 0.004) was observed between controls and patients. Bacterial communities within patients with PBB were dominated by Proteobacteria, and indicator species analysis showed that Haemophilus and Neisseria were significantly associated with the patient group. In 15 (52.9%) cases the dominant organism by sequencing was not identified by standard routine clinical culture.\n\nThe bacteria present in the lungs of patients with persistent bacterial bronchitis were less diverse in terms of richness and evenness. The results validate the clinical diagnosis, and suggest that more attention to bacterial communities in children with chronic cough may lead to more rapid recognition of this condition with earlier treatment and reduction in disease burden.",2017-08-29,"Cuthbertson, L.; Craven, V.; Bingle, L.; Cookson, W. O. C. M.; Everard, M. L.; Moffatt, M. F.",,,,True
138d4617f4f4984bec9cf2c7540fed533d9e4d6e,biorxiv,Automated collection of pathogen-specific diagnostic data for real-time syndromic epidemiological studies,doi.org/10.1101/157156,,,See https://www.biorxiv.org/about-biorxiv,"Health-care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are pathogen-specific. We describe a system, FilmArray(R) Trend, for rapid disease reporting that is syndrome-based but pathogen-specific. Results from a multiplex molecular diagnostic test are sent directly to a cloud database. www.syndromictrends.com presents these data in near real-time. Trend preserves patient privacy by removing or obfuscating patient identifiers. We summarize the respiratory pathogen results, for 20 organisms from 344,000 patient samples acquired as standard of care testing over the last four years from 20 clinical laboratories in the United States. The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks and adenovirus and bacterial pathogens show constant detection over the year. Interestingly, the rate of pathogen co-detections, on average 7.7%, matches predictions based on the relative abundance of organisms present.",2017-09-22,"Meyers, L.; Ginocchio, C. C.; Faucett, A. N.; Nolte, F. S.; Gesteland, P. H.; Leber, A.; Janowiak, D.; Donovan, V.; Dien Bard, J.; Spitzer, S.; Stellrecht, K. A.; Salimnia, H.; Selvarangan, R.; Juretschko, S.; Daly, J. A.; Wallentine, J. C.; Lindsey, K.; Moore, F.; Reed, S. L.; Aguero-Rosenfeld, M.; Fey, P. D.; Storch, G. A.; Melnick, S. J.; Robinson, C. C.; Meredith, J. F.; Cook, C. V.; Nelson, R. K.; Jones, J. D.; Scarpino, S. V.; Althouse, B. M.; Ririe, K. M.; Malin, B. A.; Poritz, M. A.",,,,True
9b17a9fa6be11d8b3dbed9f3dea2516020083bd3,biorxiv,FastViromeExplorer: A Pipeline for Virus and Phage Identification and Abundance Profiling in Metagenomics Data,doi.org/10.1101/196998,,,See https://www.biorxiv.org/about-biorxiv,"Identifying viruses and phages in a metagenomics sample has important implication in improving human health, preventing viral outbreaks, and developing personalized medicine. With the rapid increase in data files generated by next generation sequencing, existing tools for identifying and annotating viruses and phages in metagenomics samples suffer from expensive running time. In this paper, we developed a stand-alone pipeline, FastViromeExplorer, for rapid identification and abundance quantification of viruses and phages in big metagenomic data. Both real and simulated data validated FastViromeExplorer as a reliable tool to accurately identify viruses and their abundances in large data, as well as in a time efficient manner.",2017-10-03,"Tithi, S. S.; Jensen, R. V.; Zhang, L.",,,,True
7395de48b2402e5e1561a93b99e8aae8728c6ff1,biorxiv,RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination,doi.org/10.1101/200410,,,See https://www.biorxiv.org/about-biorxiv,"TRIM25 is a novel RNA-binding protein and a member of the Tripartite Motif (TRIM) family of E3 ubiquitin ligases, which plays a pivotal role in the innate immune response. Almost nothing is known about its RNA-related roles in cell biology. Furthermore, its RNA-binding domain has not been characterized. Here, we reveal that RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain, which we postulate to be a novel RNA-binding domain. Using CLIP-seq and SILAC-based co-immunoprecipitation assays, we uncover TRIM25s endogenous RNA targets and protein binding partners. Finally, we show that the RNA-binding activity of TRIM25 is important for its ubiquitin ligase function. These results reveal new insights into the molecular roles and characteristics of RNA-binding E3 ubiquitin ligases and demonstrate that RNA could be an essential factor for their biological functions.",2017-10-09,"Roy Choudhury, N.; Heikel, G.; Trubitsyna, M.; Kubik, P.; Nowak, J. S.; Webb, S.; Granneman, S.; Spanos, C.; Rappsilber, J.; Castello Palomares, A.; Michlewski, G.",,,,True
f634f2b73197fdda1d444dcdd6bd84a96ea148ad,biorxiv,Viral fitness predicts the magnitude and direction of perturbations in the infected host transcriptome,doi.org/10.1101/206789,,,See https://www.biorxiv.org/about-biorxiv,"Determining the fitness of viral genotypes has become a standard practice in virology as it is essential to evaluate their evolutionary potential. Darwinian fitness, defined as the advantage of a given genotype with respect to a reference one, is a mesoscopic property that captures into a single figure differences in performance at every stage of viral infection. But to which extent viral fitness results from particular molecular interactions with host factors and regulatory networks during infection? Can we identify host genes, and then functional classes, whose expression depends on viral fitness? Here, we compared the transcriptomes of tobacco plants infected with seven genotypes of tobacco etch potyvirus (TEV) that differ in fitness. We found that the larger the fitness differences among genotypes, the more dissimilar the transcriptomic profiles are. Consistently, two different mutations, one in the viral RNA polymerase and another in the viral suppressor of RNA silencing, that led to close fitness values, also resulted in significantly similar gene expression profiles. Moreover, we identified host genes whose expression showed a significant correlation, positive or negative, with TEV fitness. Over-expression of genes with positive correlation activates hormone-and RNA silencing-mediated pathways of plant defense. By contrast, under-expression of genes negatively correlated reduces metabolism, growth, and development. Overall, these results reveal the high information content of viral fitness, and suggest its potential use to predict differences in genomic profiles of infected hosts.",2017-10-20,"Cervera, H.; Ambros, S.; Bernet, G. P.; Rodrigo, G.; Elena, S.",,,,True
620d69e419e3c8756de8bf96d86f6bf0de7ed919,biorxiv,Neuronal CCL2 expression drives inflammatory monocyte infiltration into the brain during acute virus infection,doi.org/10.1101/208587,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundViral encephalitis is a dangerous compromise between the need to robustly clear pathogen from the brain and the need to protect neurons from bystander injury. Theiler's murine encephalomyelitis virus (TMEV) infection of C57Bl/6 mice is a model of viral encephalitis in which the compromise results in hippocampal damage and permanent neurological sequelae. We previously identified brain infiltrating inflammatory monocytes as the primary driver of this hippocampal pathology, but the mechanisms involved in recruiting these cells to the brain were unclear.\n\nMethodsChemokine expression levels in the hippocampus were assessed by microarray, ELISA, RT-PCR, and immunofluorescence. Monocyte infiltration during acute TMEV infection was measured by flow cytometry. CCL2 levels were manipulated by immunodepletion and by specific removal from neurons in mice generated by crossing a line expressing the Cre recombinase behind the synapsin promoter to animals with floxed CCL2.\n\nResultsInoculation of the brain with TMEV induced hippocampal production of the proinflammatory chemokine CCL2 that peaked at 6 hours postinfection, whereas inoculation with UV-inactivated TMEV did not elicit this response. Immunofluorescence revealed that hippocampal neurons expressed high levels of CCL2 at this timepoint. Genetic deletion of CCR2 and systemic immunodepletion of CCL2 abrogated or blunted the infiltration of inflammatory monocytes into the brain during acute infection. Specific genetic deletion of CCL2 from neurons reduced serum and hippocampal CCL2 levels and inhibited inflammatory monocyte infiltration into the brain.\n\nConclusionsWe conclude that intracranial inoculation with infectious TMEV rapidly induces the expression of CCL2 in neurons, and this cellular source is necessary for CCR2-dependent infiltration of inflammatory monocytes into the brain during the most acute stage of encephalitis. These findings highlight a unique role for neuronal production of chemokines in the initiation of leukocytic infiltration into the infected central nervous system.",2017-10-25,"Howe, C. L.; LaFrance-Corey, R. G.; Goddery, E. N.; Mirchia, K.",,,,True
41fc7191573c2f01fdef9c8ebb072e5f54cbb598,biorxiv,Coordination between discrete Mitotic Arrest Deficient 1 (MAD1) domains is required for efficient mitotic checkpoint signaling,doi.org/10.1101/212704,,,See https://www.biorxiv.org/about-biorxiv,"As a sensitive signaling system, the mitotic checkpoint ensures faithful chromosome segregation by delaying anaphase onset when even a single kinetochore is unattached. The key signal amplification reaction for the checkpoint is the conformational conversion of open MAD2 (O-MAD2) into closed MAD2 (C-MAD2). The reaction was suggested to be catalyzed by an unusual catalyst, a MAD1:C-MAD2 tetramer, but how the catalysis is executed and regulated remains elusive. Here we report that in addition to the well-characterized middle region (MIM), both amino- and carboxyl-terminal domains (NTD and CTD) of MAD1 also contribute to the mitotic checkpoint. In contrast to MIM that stably associates with C-MAD2, MAD1-NTD and CTD surprisingly bind to both O-MAD2 and C-MAD2, suggesting their interactions with substrates and products of the O-C conversion. MAD1-NTD also interacts with CTD. MPS1 kinase interacts with and phosphorylates both NTD and CTD. The phosphorylation reduces the NTD:CTD interaction and CTD interaction with MPS1. Mutating CTD phosphorylation sites including Thr716 compromises MAD2 binding and the checkpoint responses. Ser610 and Tyr634 also contribute to the checkpoint. Our results have uncovered previously unknown interactions of MAD1-NTD and CTD with MAD2 conformers and their regulation by MPS1 kinase, providing novel insights into the mitotic checkpoint signaling.",2017-11-01,"Ji, W.; Luo, Y.; Ahmad, E.; Liu, S.-T.",,,,True
3c70c99afc7a38df3c4807857856ea258d378429,biorxiv,The molecular basis for Pompe disease revealed by the structure of human acid α-glucosidase,doi.org/10.1101/212837,,,See https://www.biorxiv.org/about-biorxiv,"Pompe disease results from a defect in human acid -glucosidase (GAA), a lysosomal enzyme that cleaves terminal 1-4 and 1-6 glucose from glycogen. In Pompe disease (also known as Glycogen Storage Disorder type II), the accumulation of undegraded glycogen in lysosomes leads to cellular dysfunction, primarily in muscle and heart tissues. Pompe disease is an active candidate of clinical research, with pharmacological chaperone therapy tested and enzyme replacement therapy approved. Despite production of large amounts of recombinant GAA annually, the structure of GAA has not been reported until now. Here, we describe the first structure of GAA, at 1.7[A] resolution. Three structures of GAA complexes reveal the molecular basis for the hundreds of mutations that lead to Pompe disease and for pharmacological chaperoning in the protein. The GAA structure reveals a surprising second sugar-binding site 34[A] from the active site, suggesting a possible mechanism for processing of large glycogen substrates. Overall, the structure will assist in the design of next-generation treatments for Pompe disease.",2017-11-01,"Deming, D.; Lee, K.; McSherry, T.; Wei, R. R.; Edmunds, T.; Garman, S. C.",,,,True
d618a596def847bdfc19991c694e09bdeccf2287,biorxiv,Stochastic dynamics of an epidemics with recurrent spillovers from an endemic reservoir,doi.org/10.1101/213579,,,See https://www.biorxiv.org/about-biorxiv,"Most emerging human infectious diseases have an animal origin. Yet, while zoonotic diseases originate from a primary reservoir, most theoretical studies have principally focused on single-host processes, either exclusively humans or exclusively animals, without considering the importance of animal to human transmission for understanding the dynamics of emerging infectious diseases. Here we aim to investigate the importance of spillover transmission for explaining the number and the size of outbreaks. We propose a simple stochastic Susceptible-Infected-Recovered model with a recurrent infection of an incidental host from a reservoir (e.g. humans by a zoonotic species), considering two modes of transmission, (1) animal-to-human and (2) human-to-human. The model assumes that (i) epidemiological processes are faster than other processes such as demographics or pathogen evolution and (ii) that an epidemic occurs until there are no susceptible individuals left. The results show that during an epidemic, even when the pathogens are barely contagious, multiple outbreaks are observed due to spillover transmission. Overall, the findings demonstrate that the only consideration of direct transmission between individuals is not sufficient to explain the dynamics of zoonotic pathogens in an incidental host.",2017-11-03,"Voinson, M.; Alvergne, A.; Billiard, S.; Smadi, C.",,,,True
90e9a600cb6a0c0229a03c90d97420753676df6f,biorxiv,Large protein complex production using the SmartBac System - Strategies and Applications,doi.org/10.1101/219246,,,See https://www.biorxiv.org/about-biorxiv,"Recent revolution of cryo-electron microscopy has opened a new door to solve high-resolution structures of macromolecule complexes without crystallization while how to efficiently obtain homogenous macromolecule complex sample is therefore becoming a bottleneck. Here we report SmartBac, an easy and versatile system for constructing large-sized transfer plasmids used to generate recombinant baculoviruses that express large multiprotein complexes in insect cells. The SmartBac system integrates the univector plasmid-fusion system, Gibson assembly method and polyprotein strategy to construct the final transfer plasmids. The fluorescent proteins are designed to be co-expressed with recombinant proteins to monitor transfection and expression efficiencies. A scheme of screening an optimal tagged subunit for effective purification is provided. Six large multiprotein complexes including the human exocyst complex and dynactin complex were successfully expressed, suggesting a great potential of SmartBac for its wide application in the future structural biology study.",2017-11-14,"Zhai, Y.; Zhang, D.; Yu, L.; Sun, F.; Sun, F.",,,,False
4b1a08339bb5508f830e09f1a2c3a8022526cce0,biorxiv,Airway IRF7hi versus IRF7lo molecular response patterns determine clinical phenotypes in children with acute wheezing,doi.org/10.1101/222950,,,See https://www.biorxiv.org/about-biorxiv,"Asthma exacerbations are triggered by rhinovirus infections. We employed a systems biology approach to delineate upper airway gene network patterns underlying asthma exacerbation phenotypes in children. Cluster analysis unveiled distinct IRF7hi versus IRF7lo molecular phenotypes, the former exhibiting robust upregulation of Th1/type I interferon responses and the latter an alternative signature marked by upregulation of cytokine and growth factor signalling and downregulation of interferon gamma. The two phenotypes also produced distinct clinical phenotypes. For IRF7lo versus IRF7hi: symptom duration prior to hospital presentation was more than twice as long from initial symptoms (p=0.011) and nearly three times as long for cough (p<0.001); the odds ratio of admission to hospital was increased more than four-fold (p=0.018); and time to recurrence was shorter (p=0.015). In summary, our findings demonstrate that asthma exacerbations in children can be divided into IRF7hi versus IRF7lo phenotypes with associated differences in clinical phenotypes.\n\nAbbreviationsAHR, airway hyperresponsiveness; ARG1, Arginase 1, CSF3, Colony Stimulating Factor 3; CD38, Cluster of Differentiation 38; CD163, Cluster of Differentiation 163; cDCs, conventional (or myeloid) dendritic cells; DDX60, DExD/H-Box Helicase 60; ED, Emergency Department; EGF, Epidermal Growth Factor; ERK, Extracellular signal-Regulated Kinase; FCER1G, Fc Fragment Of IgE Receptor Ig; HMBS, Hydroxymethylbilane Synthase; IFNg, Interferon Gamma; IFNL1, Interferon Lambda 1; IL-1R2, Interleukin 1 Receptor Type 2; IRF7, Interferon Regulatory Factor 7; ISG15, Interferon-stimulated gene 15; MDA5, Melanoma Differentiation-Associated protein 5; MX1, Myxovirus Resistance Protein 1; NAD, nicotinamide adenine dinucleotide; NCR1, Natural cytotoxicity triggering receptor 1; OSM, Oncostatin M; PD-L1, Programmed Death-Ligand 1; PPIA, Peptidylprolyl Isomerase A; PPIB Peptidylprolyl Isomerase B; RSAD2, Radical S-adenosyl methionine domain-containing protein 2; RSV, respiratory syncytial virus; RT-qPCR, quantitative reverse transcription PCR; RV, rhinovirus; sPLA2, secretory Phospholipase A2; TGFb, Transforming Growth Factor beta; THBS1, Thrombospondin 1; TNF, Tumor Necrosis Factor; TLR2, Toll-like Receptor 2.",2017-11-21,"Khoo, K.; Read, J.; Franks, K.; Zhang, G.; Bizzintino, J.; Coleman, L.; McCrae, C.; Oberg, L.; Troy, N.; Prastanti, F.; Everard, J.; Oo, S.; Borland, M.; Maciewicz, R.; Le Seouf, P.; Laing, I.; Bosco, A.",,,,True
3b22eecad8a582436c52284a4db2198a98a94e18,biorxiv,"DUSP1 regulates apoptosis and cell migration, but not the JIP1-protected cytokine response, during Respiratory Syncytial Virus and Sendai Virus infection",doi.org/10.1101/163360,,,See https://www.biorxiv.org/about-biorxiv,"The host antiviral response involves the induction of interferons and proinflammatory cytokines, but also the activation of cell death pathways, including apoptosis, to limit viral replication and spreading. This host defense is strictly regulated to eliminate the infection while limiting tissue damage that is associated with virus pathogenesis. Post-translational modifications, most notably phosphorylation, are key regulators of the antiviral defense implying an important role of protein phosphatases. Here, we investigated the role of the dual-specificity phosphatase 1 (DUSP1) in the host defense against human respiratory syncytial virus (RSV), a pathogenic virus of the Pneumoviridae family, and Sendai virus (SeV), a model virus being developed as a vector for anti-RSV vaccine. We found that DUSP1 is upregulated before being subjected to proteasomal degradation. DUSP1 does not inhibit the antiviral response, but negatively regulates virus-induced JNK/p38 MAPK phosphorylation. Interaction with the JNK-interacting protein 1 scaffold protein prevents dephosphorylation of JNK by DUSP1, likely explaining that AP-1 activation and downstream cytokine production are protected from DUSP1 inhibition. Importantly, DUSP1 promotes SeV-induced apoptosis and suppresses cell migration in RSV-infected cells. Collectively, our data unveil a previously unrecognized selective role of DUSP1 in the regulation of tissue damage and repair during infections by RSV and SeV.",2017-11-26,"Robitaille, A. C.; Caron, E.; Zucchini, N.; Mukawera, E.; Adam, D.; Mariani, M. K.; Gelinas, A.; Fortin, A.; Brochiero, E.; Grandvaux, N.",,,,True
02201e4601ab0eb70b6c26480cf2bfeae2625193,biorxiv,The impact of regular school closure on seasonal influenza epidemics: a data-driven spatial transmission model for Belgium,doi.org/10.1101/230565,,,See https://www.biorxiv.org/about-biorxiv,"School closure is often considered as an option to mitigate influenza epidemics because of its potential to reduce transmission in children and then in the community. The policy is still however highly debated because of controversial evidence. Moreover, the specific mechanisms leading to mitigation are not clearly identified.\n\nWe introduced a stochastic spatial age-specific metapopulation model to assess the role of holiday-associated behavioral changes and how they affect seasonal influenza dynamics. The model is applied to Belgium, parameterized with country-specific data on social mixing and travel, and calibrated to the 2008/2009 influenza season. It includes behavioral changes occurring during weekend vs. weekday, and holiday vs. school-term. Several experimental scenarios are explored to identify the relevant social and behavioral mechanisms.\n\nStochastic numerical simulations show that holidays considerably delay the peak of the season and mitigate its impact. Changes in mixing patterns are responsible for the observed effects, whereas changes in travel behavior do not alter the epidemic. Weekends are important in slowing down the season by periodically dampening transmission. Christmas holidays have the largest impact on the epidemic, however later school breaks may help in reducing the epidemic size, stressing the importance of considering the full calendar. An extension of the Christmas holiday of 1 week may further mitigate the epidemic.\n\nChanges in the way individuals establish contacts during holidays are the key ingredient explaining the mitigating effect of regular school closure. Our findings highlight the need to quantify these changes in different demographic and epidemic contexts in order to provide accurate and reliable evaluations of closure effectiveness. They also suggest strategic policies in the distribution of holiday periods to minimize the epidemic impact.",2017-12-07,"De Luca, G.; Van Kerckhove, K.; Coletti, P.; Poletto, C.; Bossuyt, N.; Hens, N.; Colizza, V.",,,,True
08a22278486e12768ce186677a6a89663d24586f,biorxiv,Complemented palindrome small RNAs first discovered from SARS coronavirus,doi.org/10.1101/185876,,,See https://www.biorxiv.org/about-biorxiv,"In this study, we reported for the first time the existence of complemented palindrome small RNAs (cpsRNAs) and proposed cpsRNAs and palindrome small RNAs (psRNAs) as a novel class of small RNAs. The first discovered cpsRNA UCUUUAACAAGCUUGUUAAAGA from SARS coronavirus named SARS-CoV-cpsR-22 contained 22 nucleotides perfectly matching its reverse complementary sequence. Further sequence analysis supported that SARS-CoV-cpsR-22 originated from bat betacoronavirus. The results of RNAi experiments showed that one 19-nt segment of SARS-CoV-cpsR-22 significantly induced cell apoptosis. These results suggested that SARS-CoV-cpsR-22 could play a role in SARS-CoV infection or pathogenicity. The discovery of psRNAs and cpsRNAs paved the way to find new markers for pathogen detection and reveal the mechanisms in the infection or pathogenicity from a different point of view. The discovery of psRNAs and cpsRNAs also broaden the understanding of palindrome motifs in animal of plant genomes.",2017-12-13,"Liu, C.; Chen, Z.; Shen, W.; Yu, D.; Li, S.; Hu, Y.; Ji, H.; Bu, W.; Wang, Q.; Gao, S.",,,,True
aa5a99e67d3e887b3fa88575fb0d4a662d0a60ce,biorxiv,Modeling Epidemics: A Primer and Numerus Software Implementation,doi.org/10.1101/191601,,,See https://www.biorxiv.org/about-biorxiv,"Epidemiological models are dominated by SEIR (Susceptible, Exposed, Infected and Removed) dynamical systems formulations and their elaborations. These formulations can be continuous or discrete, deterministic or stochastic, or spatially homogeneous or heterogeneous, the latter often embracing a network formulation. Here we review the continuous and discrete deterministic and discrete stochastic formulations of the SEIR dynamical systems models, and we outline how they can be easily and rapidly constructed using the Numerus Model Builder, a graphically-driven coding platform. We also demonstrate how to extend these models to a metapopulation setting using both the Numerus Model Builder network and geographical mapping tools.",2017-12-13,"Getz, W. M.; Salter, R.; Muellerklein, O.; Yoon, H. S.; Tallam, K.",,,,True
fb7371ad31cd501854660876a282060402082537,biorxiv,MERS-CoV spillover at the camel-human interface,doi.org/10.1101/173211,,,See https://www.biorxiv.org/about-biorxiv,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus from camels causing significant mortality and morbidity in humans in the Arabian Peninsula. The epidemiology of the virus remains poorly understood, and while case-based and seroepidemiological studies have been employed extensively throughout the epidemic, viral sequence data have not been utilised to their full potential. Here we use existing MERS-CoV sequence data to explore its phylodynamics in two of its known major hosts, humans and camels. We employ structured coalescent models to show that long-term MERS-CoV evolution occurs exclusively in camels, whereas humans act as a transient, and ultimately terminal host. By analysing the distribution of human outbreak cluster sizes and zoonotic introduction times we show that human outbreaks in the Arabian peninsula are driven by seasonally varying zoonotic transfer of viruses from camels. Without heretofore unseen evolution of host tropism, MERS-CoV is unlikely to become endemic in humans.",2017-12-20,"Dudas, G.; Carvalho, L.; Rambaut, A.; Bedford, T.",,,,True
c6039f8933305c9f44a44c81a15b321b6c2848dc,biorxiv,Far-UVC light: A new tool to control the spread of airborne-mediated microbial diseases,doi.org/10.1101/240408,,,See https://www.biorxiv.org/about-biorxiv,"Airborne-mediated microbial diseases such as influenza and tuberculosis represent major public health challenges. A direct approach to prevent airborne transmission is inactivation of airborne pathogens, and the airborne antimicrobial potential of UVC ultraviolet light has long been established; however, its widespread use in public settings is limited because conventional UVC light sources are both carcinogenic and cataractogenic. By contrast, we have previously shown that far-UVC light (207-222 nm) efficiently kills bacteria without harm to exposed mammalian skin. This is because, due to its strong absorbance in biological materials, far-UVC light cannot penetrate even the outer (non living) layers of human skin or eye; however, because bacteria and viruses are of micrometer or smaller dimensions, far-UVC can penetrate and inactivate them. We show for the first time that far-UVC efficiently kills airborne aerosolized viruses, a very low dose of 2 mJ/cm2 of 222-nm light inactivating >95% of aerosolized H1N1 influenza virus. Continuous very low dose-rate far-UVC light in indoor public locations is a promising, safe and inexpensive tool to reduce the spread of airborne-mediated microbial diseases.",2017-12-28,"Welch, D.; Buonanno, M.; Grilj, V.; Shuryak, I.; Crickmore, C.; Bigelow, A. W.; Randers-Pehrson, G.; Johnson, G. W.; Brenner, D. J.",,,,True
fec0c97b9bdc012b76f082b8bcd6ba0efbb4f5c3,biorxiv,Viral gain-of-function experiments uncover residues under diversifying selection in nature,doi.org/10.1101/242495,,,See https://www.biorxiv.org/about-biorxiv,"Viral gain-of-function mutations are commonly observed in the laboratory; however, it is unknown whether those mutations also evolve in nature. We identify two key residues in the host recognition protein of bacteriophage {lambda} that are necessary to exploit a new receptor; both residues repeatedly evolved among homologs from environmental samples. Our results provide evidence for widespread host-shift evolution in nature and a proof of concept for integrating experiments with genomic epidemiology.",2018-01-03,"Maddamsetti, R.; Johnson, D. T.; Spielman, S. J.; Petrie, K. L.; Marks, D. S.; Meyer, J. R.",,,,True
4485b9462ebf52c0062692d7ab7e423c2ae05d9e,biorxiv,HCMV glycoprotein B subunit vaccine efficacy was mediated by non-neutralizing antibody effector functions,doi.org/10.1101/246884,,,See https://www.biorxiv.org/about-biorxiv,"Human cytomegalovirus (HCMV) is the most common congenital infection worldwide, frequently causing hearing loss and brain damage in afflicted infants. A vaccine to prevent maternal acquisition of HCMV during pregnancy is necessary to reduce the incidence of infant disease. The glycoprotein B (gB) + MF59 adjuvant subunit vaccine platform is the most successful HCMV vaccine tested to-date, demonstrating approximately 50% efficacy in preventing HCMV acquisition in phase II trials. However, the mechanism of vaccine protection remains unknown. Plasma from 33 gB/MF59 vaccinees at peak immunogenicity was tested for gB epitope specificity as well as neutralizing and non-neutralizing anti-HCMV effector functions, and compared to an HCMV-seropositive cohort. gB/MF59 vaccination elicited IgG responses with gB-binding magnitude and avidity comparable to natural infection. Additionally, IgG subclass distribution was similar with predominant IgG1 and IgG3 responses induced by gB vaccination and HCMV infection. However, vaccine-elicited antibodies exhibited limited neutralization of the autologous virus, negligible neutralization of multiple heterologous strains, and limited binding responses against gB structural motifs targeted by neutralizing antibodies including AD-1, AD-2, and Domain I. Interestingly, vaccinees had high-magnitude IgG responses against AD-3 linear epitopes, demonstrating immunodominance against this non-neutralizing, cytosolic region. Finally, vaccine-elicited IgG robustly bound trimeric, membrane-associated gB on the surface of transfected or HCMV-infected cells and mediated virion phagocytosis, though were poor mediators of NK cell activation. Altogether, these data suggest that non-neutralizing antibody functions, including virion phagocytosis, likely played a role in the observed 50% vaccine-mediated protection against HCMV acquisition.\n\nSignificanceThe CDC estimates that every hour, a child is born in the United States with permanent neurologic disability resulting from human cytomegalovirus (HCMV) infection - more than is caused by Down syndrome, fetal alcohol syndrome, and neural tube defects combined. A maternal vaccine to block transmission of HCMV to the developing fetus is a necessary intervention to prevent these adverse outcomes. The gB/MF59 vaccine is the most successful tested clinically to-date, achieving 50% reduction in HCMV acquisition. This manuscript establishes the function and epitope specificity of the humoral response stimulated by this vaccine that may explain the partial vaccine efficacy. Understanding the mechanism of gB/MF59-elicited protective immune responses will guide rational design and evaluation of the next generation of HCMV vaccines.",2018-01-11,"Nelson, C. S.; Huffman, T.; Cisneros de la Rosa, E.; Xi, G.; Vandergrift, N.; Pass, R. F.; Pollara, J.; Permar, S. R.",,,,True
4f392ef1aa2234dda52ab8e6540f275322a20697,biorxiv,Coronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitors,doi.org/10.1101/246991,,,See https://www.biorxiv.org/about-biorxiv,"Enveloped viruses gain entry into host cells by fusing with cellular membranes, a step required for virus replication. Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and infectious bronchitis virus (IBV), fuse at the plasma membrane or use receptor-mediated endocytosis and fuse with endosomes depending on the cell or tissue type. The virus Spike (S) protein mediates fusion with the host cell membrane. We have shown previously that an Abl kinase inhibitor, imatinib, significantly reduces SARS-CoV and MERS-CoV viral titers and prevents endosomal entry by HIV SARS S and MERS S pseudotyped virions. SARS-CoV and MERS-CoV are classified as BSL-3 viruses, which can make experimentation into the cellular mechanisms involved in infection more challenging. Here, we use IBV, a BSL-2 virus, as a model for studying the role of Abl kinase activity during coronavirus infection. We found that imatinib and two specific Abl kinase inhibitors, GNF2 and GNF5, reduce IBV titers by blocking the first round of virus infection. Additionally, all three drugs prevented IBV S-induced syncytia formation prior to the hemifusion step. Our results indicate that membrane fusion (both virus-cell and cell-cell) is blocked in the presence of Abl kinase inhibitors. Studying the effects of Abl kinase inhibitors on IBV will be useful in identifying host cell pathways required for coronavirus infection. This will provide insight into possible therapeutic targets to treat infections by current as well as newly emerging coronaviruses.",2018-01-12,"Sisk, J.; Frieman, M. B.; Machamer, C. E.",,,,True
b1e7752cbf528db99723a3a67b49b9b5c6e449af,biorxiv,Host shifts result in parallel genetic changes when viruses evolve in closely related species,doi.org/10.1101/226175,,,See https://www.biorxiv.org/about-biorxiv,"Host shifts, where a pathogen invades and establishes in a new host species, are a major source of emerging infectious diseases. They frequently occur between related host species and often rely on the pathogen evolving adaptations that increase their fitness in the novel host species. To investigate genetic changes in novel hosts, we experimentally evolved replicate lineages of an RNA virus (Drosophila C Virus) in 19 different species of Drosophilidae and deep sequenced the viral genomes. We found a strong pattern of parallel evolution, where viral lineages from the same host were genetically more similar to each other than to lineages from other host species. When we compared viruses that had evolved in different host species, we found that parallel genetic changes were more likely to occur if the two host species were closely related. This suggests that when a virus adapts to one host it might also become better adapted to closely related host species. This may explain in part why host shifts tend to occur between related species, and may mean that when a new pathogen appears in a given species, closely related species may become vulnerable to the new disease.",2018-01-12,"Longdon, B.; Day, J. P.; Alves, J. M.; Smith, S. C.; Houslay, T. M.; McGonigle, J. E.; Tagliaferri, L.; Jiggins, F. M.",,,,True
b5b029e65b963ae092dd88b21911e74b0cf557cc,biorxiv,Microbiota-independent antiviral protection conferred by aminoglycoside antibiotics,doi.org/10.1101/248617,,,See https://www.biorxiv.org/about-biorxiv,"Antibiotics are widely used to treat infections in humans. However, the impact of antibiotic use on host cells is understudied. We have identified a novel antiviral effect of commonly used aminoglycoside antibiotics. We show that mucosal application of aminoglycosides increased host resistance to a broad range of viral infections including herpes simplex viruses, influenza A virus and Zika virus. Aminoglycoside treatment also reduced viral replication in primary human cells. This antiviral activity was independent of the microbiota as aminoglycoside treatment protected germ-free mice. Microarray analysis uncovered a marked upregulation of transcripts for interferon-stimulated genes (ISGs) following aminoglycoside application. ISG induction was mediated by TLR3, and required TIR-domain-containing adapter-inducing interferon-{beta} (TRIF), signaling adaptor, and interferon regulatory factors 3 (IRF3) and IRF7, transcription factors that promote ISG expression. XCR1+ dendritic cells, which uniquely express TLR3, were recruited to the vaginal mucosa upon aminoglycoside treatment and were required for ISG induction. These results highlight an unexpected ability of aminoglycoside antibiotics to confer broad antiviral resistance in vivo.",2018-01-16,"Gopinath, S.; Kim, M. V.; Rakib, T.; Wong, P. W.; van Zandt, M.; Barry, N. A.; Kaisho, T.; Goodman, A. L.; Iwasaki, A.",,,,True
44b6eea3629b4e13595dc49813ee39a0d20dc5f2,biorxiv,Evolutionary rate shifts suggest species-specific adaptation events in HIV-1 and SIV,doi.org/10.1101/190769,,,See https://www.biorxiv.org/about-biorxiv,"The process of molecular adaptation following a cross-species virus transmission event is currently poorly understood. Here, we identified 137 protein sites that experienced deceleration in their rate of evolution along the HIV-1/SIV phylogeny, likely indicating gain-of-function and consequent adaptation. The majority of such events occurred in parallel to cross-species transmission events and varied between HIV-1 groups, indicating independent adaptation strategies. The evolutionary rate decelerations we found were particularly prominent in accessory proteins that counteract host antiviral restriction factors, suggesting that these factors are a major barrier to viral adaptation to a new host. Surprisingly, we observed that the non-pandemic HIV-1 group O, derived from gorillas, exhibited more rate deceleration events than the pandemic group M, derived from chimpanzees. We suggest that the species barrier is higher when the genetic distance of the hosts increases. Our approach paves the way for subsequent studies on cross-species transfers in other major pathogens.",2018-01-18,"Gelbart, M.; Stern, A.",,,,True
f8eee21acf147a7088fa376af6c3d85e606b47c4,biorxiv,HCAtk and pyHCA: A Toolkit and Python API for the Hydrophobic Cluster Analysis of Protein Sequences.,doi.org/10.1101/249995,,,See https://www.biorxiv.org/about-biorxiv,"Motivation: Detecting protein domains sharing no similarity to known domains, as stored in domain databases, is a challenging problem, particularly for unannotated proteomes, domains emerged recently, fast diverging proteins or domains with intrinsically disordered regions.\n\nResults: We developed pyHCA and HCAtk, a python API and standalone tool gathering together improved versions of previously developed methodologies, with new functionalities. The developed tools can be either used from command line or from a python API.\n\nAvailability: HCAtk and pyHCA are available at https://github.com/T-B-F/pyHCA under the CeCILL-C license.",2018-01-18,"Bitard-Feildel, T.; Callebaut, I.",,,,True
97a34a062a7ad09f7633d4a0e76d013b28b9b582,biorxiv,The Evolutionary History and Impact of Bacterial tRNA Modifications,doi.org/10.1101/251322,,,See https://www.biorxiv.org/about-biorxiv,"Along with tRNAs, enzymes that modify anticodon bases are a key aspect of translation across the tree of life. tRNA modifications extend wobble pairing, allowing specific (\""target\"") tRNAs to recognize multiple codons and cover for other (\""non-target\"") tRNAs, often improving translation efficiency and accuracy. However, the detailed evolutionary history and impact of tRNA modifying enzymes has not been analyzed. Using ancestral reconstruction of five tRNA modifications across 1093 bacteria, we show that most modifications were ancestral to eubacteria, but were repeatedly lost in many lineages. Most modification losses coincided with evolutionary shifts in non-target tRNAs, often driven by increased bias in genomic GC and associated codon use, or by genome reduction. In turn, the loss of tRNA modifications stabilized otherwise highly dynamic tRNA gene repertoires. Our work thus traces the complex history of bacterial tRNA modifications, providing the first clear evidence for their role in the evolution of bacterial translation.",2018-01-22,"Diwan, G. D.; Agashe, D.",,,,True
c124701d09545e0117cca7a3a5f449584223899f,biorxiv,Generating genomic platforms to study Candida albicans pathogenesis,doi.org/10.1101/261628,,,See https://www.biorxiv.org/about-biorxiv,"The advent of the genomic era has made elucidating gene function at large scale a pressing challenge. ORFeome collections, whereby almost all ORFs of a given species are cloned and can be subsequently leveraged in multiple functional genomic approaches, represent valuable resources towards this endeavor. Here we provide novel, genome-scale tools for the study of Candida albicans, a commensal yeast that is also responsible for frequent superficial and disseminated infections in humans. We have generated an ORFeome collection composed of 5,102 ORFs cloned in a Gateway donor vector, representing 83% of the currently annotated coding sequences of C. albicans. Sequencing data of the cloned ORFs are available in the CandidaOrfDB database at http://candidaorfeome.eu. We also engineered 49 expression vectors with a choice of promoters, tags, and selection markers and demonstrated their applicability to the study of target ORFs transferred from the C. albicans ORFeome. In addition, the use of the ORFeome in the detection of protein-protein interaction was demonstrated. Mating-compatible strains as well as Gateway-compatible two-hybrid vectors were engineered, validated and used in a proof of concept experiment. These unique and valuable resources should greatly facilitate future functional studies in C. albicans and the elucidation of mechanisms that underlie its pathogenicity.",2018-02-08,"Legrand, M.; Bachellier-Bassi, S.; Lee, K. K.; Chaudhari, Y.; Tournu, H.; Arbogast, L.; Boyer, H.; Chauvel, M.; Cabral, V.; Maufrais, C.; Nesseir, A.; Maslanka, I.; Permal, E.; Rossignol, T.; Walker, L. A.; Zeidler, U.; Znaidi, S.; Schoeters, F.; Majgier, C.; Julien, R. A.; Ma, L.; Tichit, M.; Bouchier, C.; Van Dijck, P.; Munro, C. A.; d'Enfert, C.",,,,True
7d98a73314cd9f923aaa367f3f4de056b8cedec5,biorxiv,IFIT3 and IFIT2/3 promote IFIT1-mediated translation inhibition by enhancing binding to non-self RNA.,doi.org/10.1101/261776,,,See https://www.biorxiv.org/about-biorxiv,"Interferon-induced proteins with tetratricopeptide repeats (IFITs) are highly expressed during the cell-intrinsic immune response to viral infection. IFIT1 inhibits translation by binding directly to the 5' end of foreign RNAs, particularly those with non-self cap structures, precluding the recruitment of the cap-binding eukaryotic translation initiation factor 4F and subsequent 40S recruitment. Interaction of different IFIT family members is well described, but little is known of the molecular basis of IFIT association or its impact on function. Here, we reconstituted different complexes of IFIT1, IFIT2 and IFIT3 in vitro, which enabled us to reveal critical aspects of IFIT complex assembly. IFIT1 interacts rapidly and strongly with IFIT3 forming a stable heterotetramer. IFIT2 and IFIT3 homodimers dissociate to form a more stable heterodimer that associates with IFIT1, forming an IFIT1:IFIT2:IFIT3 trimer. Site-directed mutagenesis revealed a C-terminal  YxxxL motif in IFIT1 that mediates its association with IFIT3. Using various reporter mRNAs, we demonstrate for the first time that IFIT3 stabilises IFIT1 binding to cap0-mRNA and enhances its translation inhibition activity. Disrupting the binding interface between IFIT1 and IFIT3 abrogated this enhancement. This work reveals molecular aspects of IFIT assembly and provides an important  missing link between IFIT interaction and function.",2018-02-08,"Fleith, R. C.; Mears, H. V.; Emmott, E.; Graham, S. C.; Mansur, D. S.; Sweeney, T. R.",,,,True
4151e9b4ea5395d73bf33309dbca26551cc7c657,biorxiv,Gene expression is stronger associated with behaviour than with age and fertility in ant workers,doi.org/10.1101/267336,,,See https://www.biorxiv.org/about-biorxiv,"The ecological success of social insects is based on division of labour, not only between queens and workers, but also among workers. Whether a worker tends the brood or forages is strongly influenced by age, fertility and nutritional status, with brood carers being younger, more fecund and corpulent. Here, we experimentally disentangle behaviour from age and fertility in Temnothorax longispinosus ant workers and analyse how these parameters are linked to whole-body gene expression. Our transcriptome analysis reveals four times more genes associated with behaviour than with age and only few fertility-associated genes. Brood carers exhibited an upregulation of genes involved in lipid biosynthesis, whereas foragers invested in metabolism. Additional simulations revealed that the experimental disassociation of co-varying factors reduces transcriptomic noise, potentially explaining discrepancies between transcriptomic studies on worker behaviour in other social insects. Our study highlights the influence of nutritional status on task choice in ant workers.",2018-02-18,"Kohlmeier, P.; Alleman, A. R.; Libbrecht, R.; Foitzik, S.; Feldmeyer, B.",,,,True
46030e9b8451bf3b0c90833dbeacce286a263a09,biorxiv,An Augmented Aging Process in Brain White Matter in HIV,doi.org/10.1101/265199,,,See https://www.biorxiv.org/about-biorxiv,"ObjectiveHIV infection and aging are both associated with neurodegeneration. However, whether the aging process alone or other factors associated with advanced age account for the progression of neurodegeneration in the aging HIV-positive (HIV+) population remains unclear.\n\nMethodsHIV+ (n=70) and HIV-negative (HIV-, n=34) participants underwent diffusion tensor imaging (DTI) and metrics of microstructural properties were extracted from regions of interest (ROIs). A support vector regression model was trained on two independent datasets of healthy adults across the adult life-span (n=765, Cam-CAN = 588; UiO = 177) to predict participant age from DTI metrics, and applied to the HIV dataset. Predicted brain age gap (BAG) was computed as the difference between predicted age and chronological age, and statistically compared between HIV groups. Regressions assessed the relationship between BAG and HIV severity/medical comorbidities. Finally, correlation analyses tested for associations between BAG and cognitive performance.\n\nResultsBAG was significantly higher in the HIV+ group than the HIV-group F (1, 103) = 12.408, p = 0.001). HIV RNA viral load was significantly associated with BAG, particularly in older HIV+ individuals (R2 = 0.29, F(7, 70) = 2.66, p = 0.021). Further, BAG was negatively correlated with domain-level cognitive function (learning: r = -0.26, p = 0.008; memory: r = -0.21, p = 0.034).\n\nConclusionsHIV infection is associated with augmented white matter aging, and greater brain aging is associated with worse cognitive performance in multiple domains.",2018-02-22,"Kuhn, T.; Kaufmann, T.; Doan, N. T.; Westlye, L. T.; Jones, J. D.; Nunez, R. A.; Bookheimer, S. Y.; Singer, E. J.; Hinkin, C. H.; Thames, A. D.",,,,True
26b541f188bd6f6525fd700b69fdb4329392b02a,biorxiv,Simultaneous detection of DNA and RNA virus species involved in bovine respiratory disease by PCR-free rapid tagmentation-based library preparation and MinION nanopore sequencing,doi.org/10.1101/269936,,,See https://www.biorxiv.org/about-biorxiv,"AbstactThe Oxford Nanopore MinION Mk1B is a portable 90 g device that sequences DNA directly at 450 bases/second generating sequence reads in excess of 400 kb. Recent improvements in error rate and speed of library preparation mean that this device has considerable potential for rapid molecular bovine pathogen diagnostics. We tested the MinION for rapid untargeted detection of viral pathogens associated with bovine respiratory disease (BRD), an economically important disease often involving primary infection of the lung by one or more of a number of DNA and/or RNA viruses. We combined three foetal lung cell cultures which were infected with either Bovine Respiratory Syncytial Virus (BRSV), Bovine Herpes Virus 1 (BoHV1) or Bovine Parainfluenza Virus 3 (BPI-3). BoHV1 is a DNA virus and BPI-3 and BRSV are RNA viruses. The cell cultures were treated with DNase and RNase to deplete bovine nucleic acid prior to viral nucleic acid extraction and double-stranded cDNA synthesis. Sequencing libraries were generated by PCR-free tagmentation in under 10 minutes and loaded onto a MinION sequencer. Approximately 7,000 sequencing reads were generated and analysed using high-throughput local BLAST against the NCBI nr/nt database. The top BLAST hit for 2,937 of these reads was identified as a virus. Of these, 2,926 (99.6%) were correctly identified either as BoHV1, BRSV or BPI-3.",2018-02-22,"McCabe, M.; Cormican, P.; Johnston, D.; Earley, B.",,,,False
7ea2f1ca7b3c2370d413ae990eb71b2b990c91fe,biorxiv,Clearing the FoG: Antifungal tolerance is a subpopulation effect that is distinct from resistance and is associated with persistent candidemia,doi.org/10.1101/206359,,,See https://www.biorxiv.org/about-biorxiv,"Drug susceptibility, defined by the minimal inhibitory concentration (MIC), often does not predict whether fungal infections will respond to therapy in the clinic. Tolerance at supra-MIC antifungal drug concentrations is rarely quantified and current clinical recommendations suggest it be ignored. Here, we measured and characterized drug-response variables that could influence the outcomes of fungal infections and be generalizable across major clades of Candida albicans, one of the most frequently isolated human fungal pathogens. We quantified antifungal tolerance as the fraction of growth (FoG) above the MIC and found that it is clearly distinct from susceptibility/resistance measured as MIC. Instead, tolerance is due to the slow growth of subpopulations of cells that overcome drug stress more efficiently than the rest of the population, and correlates inversely with the accumulation of intracellular drug. Importantly, many adjuvant drugs used together with fluconazole, a fungistatic drug, reduce tolerance without affecting resistance. These include inhibitors of major stress response hubs such as Hsp90, calcineurin, PKC1 and TOR. Accordingly, in an invertebrate infection model, adjuvant combination therapy was significantly more effective than fluconazole alone in treating highly tolerant isolates and did not improve the treatment of isolates with low tolerance levels. Furthermore, isolates recovered from immunocompetent patients with persistent candidemia displayed significantly higher tolerance than isolates that were readily cleared by fluconazole. Thus, tolerance correlates with the response to fluconazole therapy in patients and may help predict whether infections will respond to fluconazole alone. Similarly, measuring tolerance may provide a useful clinical parameter for choosing appropriate therapeutic strategies to overcome persistent clinical candidemia.",2018-03-02,"Rosenberg, A.; Ene, I. V.; Bibi, M.; Zakin, S.; Segal, E. S.; Ziv, N.; Dahan, A.; Colombo, A. L.; Bennett, R. J.; Berman, J. G.",,,,True
fb82658bed4bd076ac6d9b04baa10bfc209fa5c8,biorxiv,"Membrane proteins with high N-glycosylation, high expression, and multiple interaction partners were preferred by mammalian viruses as receptors",doi.org/10.1101/271171,,,See https://www.biorxiv.org/about-biorxiv,"Receptor mediated entry is the first step for viral infection. However, the relationship between viruses and receptors is still obscure. Here, by manually curating a high-quality database of 268 pairs of mammalian virus-host receptor interaction, which included 128 unique viral species or sub-species and 119 virus receptors, we found the viral receptors were structurally and functionally diverse, yet they had several common features when compared to other cell membrane proteins: more protein domains, higher level of N-glycosylation, higher ratio of self-interaction and more interaction partners, and higher expression in most tissues of the host. Additionally, the receptors used by the same virus tended to co-evolve. Further correlation analysis between viral receptors and the tissue and host specificity of the virus shows that the virus receptor similarity was a significant predictor for mammalian virus cross-species. This work could deepen our understanding towards the viral receptor selection and help evaluate the risk of viral zoonotic diseases.",2018-03-08,"Zhang, Z.; Zhu, Z.; Chen, W.; Cai, Z.; Xu, B.; Tan, Z.; Wu, A.; Ge, X.; Guo, X.; Tan, Z.; Xia, Z.; Zhu, H.; Jiang, T.; Peng, Y.",,,,False
05082393ba4c7ec530190dd887d99c74fd72f6d6,biorxiv,Self-assembly of the RZZ complex into filaments drives kinetochore expansion in the absence of microtubule attachment,doi.org/10.1101/282707,,,See https://www.biorxiv.org/about-biorxiv,"The kinetochore is a dynamic multi-protein assembly that forms on each sister chromatid and interacts with microtubules of the mitotic spindle to drive chromosome segregation. In animals, kinetochores without attached microtubules expand their outermost layer into crescent and ring shapes to promote microtubule capture and spindle assembly checkpoint (SAC) signalling. Kinetochore expansion is an example of protein co-polymerization, but the mechanism is not understood. Here, we present evidence that kinetochore expansion is driven by oligomerization of the Rod-Zw10-Zwilch (RZZ) complex, an outer kinetochore component that recruits the motor dynein and the SAC proteins Mad1-Mad2. Depletion of ROD in human cells suppresses kinetochore expansion, as does depletion of Spindly, the adaptor that connects RZZ to dynein, while dynein itself is dispensable. Expansion is also suppressed by mutating ZWILCH residues implicated in Spindly binding. Conversely, supplying cells with excess ROD facilitates kinetochore expansion under otherwise prohibitive conditions. Using the C. elegans early embryo, we demonstrate that ROD-1 has a concentration-dependent propensity for oligomerizing into {micro}m-scale filaments, and we identify the ROD-1 {beta}-propeller as a key regulator of self-assembly. Finally, we show that a minimal ROD-1-Zw10 complex efficiently oligomerizes into filaments in vitro. Our results suggest that RZZs capacity for oligomerization is harnessed by kinetochores to assemble the expanded outermost domain, in which RZZ filaments serve as recruitment platforms for SAC components and microtubule-binding proteins. Thus, we propose that RZZ self-assembly into filaments underlies the adaptive change in kinetochore size that contributes to chromosome segregation fidelity.",2018-03-15,"Gassmann, R.; Pereira, C.; Reis, R. M.; Gama, J. B.; Cheerambathur, D. K.; Carvalho, A. X.",,,,True
b1ce6ca5960cb799403188ca303a364428f812d8,biorxiv,Direct nucleic acid analysis of mosquitoes for high fidelity species identification and detection of Wolbachia using a cellphone,doi.org/10.1101/291849,,,See https://www.biorxiv.org/about-biorxiv,"Manipulation of natural mosquito populations using the endosymbiotic bacteria Wolbachia is being investigated as a novel strategy to reduce the burden of mosquito-borne viruses. To evaluate the efficacy of these interventions, it will be critical to determine Wolbachia infection frequencies in Aedes aegypti mosquito populations. However, current diagnostic tools are not well-suited to fit this need. Morphological methods cannot identify Wolbachia, immunoassays often suffer from low sensitivity and poor throughput, while PCR and spectroscopy require complex instruments and technical expertise, which restrict their use to centralized laboratories. To address this unmet need, we have used loop-mediated isothermal amplification (LAMP) and oligonucleotide strand displacement (OSD) probes to create a one-pot sample-to-answer nucleic acid diagnostic platform for vector and symbiont surveillance. LAMP-OSD assays can directly amplify target nucleic acids from macerated mosquitoes without requiring nucleic acid purification and yield specific single endpoint yes/no fluorescence signals that are observable to eye or by cellphone camera. We demonstrate cellphone-imaged LAMP-OSD tests for two targets, the Aedes aegypti cytochrome oxidase I (coi) gene and the Wolbachia surface protein (wsp) gene, and show a limit of detection of 4 and 40 target DNA copies, respectively. In a blinded test of 90 field-caught mosquitoes, the coi LAMP-OSD assay demonstrated 98% specificity and 97% sensitivity in identifying Ae. aegypti mosquitoes even after 3 weeks of storage without desiccant at 37 {degrees}C. Similarly, the wsp LAMP-OSD assay readily identified the wAlbB Wolbachia strain in field-collected Aedes albopictus mosquitoes without generating any false positive signals. Modest technology requirements, minimal execution steps, simple binary readout, and robust accuracy make the LAMP-OSD-to-cellphone assay platform well suited for field vector surveillance in austere or resource-limited conditions.\n\nAuthor summaryMosquitoes spread many human pathogens and novel approaches are required to reduce the burden of mosquito-borne disease. One promising approach is transferring Wolbachia into Aedes aegypti mosquitoes where it blocks transmission of arboviruses like dengue, Zika and Yellow fever viruses and spreads through mosquito populations. For effective evaluation of this approach, regular surveillance of Wolbachia infections in Ae. aegypti is required, but current diagnostic tools are not well suited to support these critical surveillance needs. To fill this need we developed a simple, robust and inexpensive assay to identify Ae. aegypti mosquitoes and Wolbachia using our unique one-pot assay platform, LAMP-OSD, which uses loop-mediated isothermal amplification to amplify nucleic acid targets at a single temperature. Unlike other LAMP-based tests, our assays assure accuracy by coupling amplification with novel nucleic acid strand displacement (OSD) probes that hybridize to specific sequences in LAMP amplification products and thereby generate simple yes/no readout of fluorescence readable by human eye and by off-the-shelf cellphones. To facilitate field use, we developed our assays so they are compatible with crushed mosquito homogenate as the template, meaning no nucleic acid extraction is required. In blinded tests using field collected mosquitoes, LAMP-OSD-cellphone tests performed robustly to identify 29 of 30 Ae. aegypti even after 3 weeks of storage at 37 {degrees}C while producing only one false positive out of 60 non-specific mosquitoes. Similarly, our assay could identify Wolbachia in field-caught Aedes albopictus without producing any false positives. Our easy to use and easy to interpret assays should facilitate widespread field mosquito surveillance with minimal instrumentation and high accuracy.",2018-03-29,"Bhadra, S.; Riedel, T. E.; Saldana, M. A.; Hegde, S.; Pederson, N.; Hughes, G. L.; Ellington, A. D.",,,,True
331a7033bb8e6d4618e4e83b74aff1aec42764a6,biorxiv,Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children,doi.org/10.1101/291864,,,See https://www.biorxiv.org/about-biorxiv,"RATIONALEDespite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant morbidity and mortality.\n\nOBJECTIVESTo develop a highly sensitive metagenomic next generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children.\n\nMETHODSWe collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 childrens hospitals from 2014-2016. Samples underwent mechanical homogenization, paired RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the NCBI nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort.\n\nMEASUREMENTS & MAIN RESULTSWe identified a rich cross-domain pulmonary microbiome containing bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median 0.58, IQR 0.33-0.62 vs. median 0.94, IQR 0.93-0.95, p<0.001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (p<0.001).\n\nCONCLUSIONSAn optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease.",2018-03-29,"Zinter, M. S.; Dvorak, C. C.; Mayday, M. Y.; Iwanaga, K.; Ly, N. P.; McGarry, M. E.; Church, G. D.; Faricy, L. E.; Rowan, C. M.; Hume, J. R.; Steiner, M. E.; Crawford, E. D.; Langelier, C.; Kalantar, K.; Chow, E. D.; Miller, S.; Shimano, K.; Melton, A.; Yanik, G. A.; Sapru, A.; DeRisi, J. L.",,,,True
1eaa329f608055620a57e6273e9d1c409de1e9ee,biorxiv,Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome,doi.org/10.1101/290874,,,See https://www.biorxiv.org/about-biorxiv,"ATP-dependent chromatin remodelling proteins represent a diverse family of proteins that share ATPase domains that are adapted to regulate protein-DNA interactions. Here we present structures of the yeast Chd1 protein engaged with nucleosomes in the presence of the transition state mimic ADP-beryllium fluoride. The path of DNA strands through the ATPase domains indicates the presence of contacts conserved with single strand translocases and additional contacts with both strands that are unique to Snf2 related proteins. The structure provides connectivity between rearrangement of ATPase lobes to a closed, nucleotide bound state and the sensing of linker DNA. Two turns of linker DNA are prised off the surface of the histone octamer as a result of Chd1 binding, and both the histone H3 tail and ubiquitin conjugated to lysine 120 are re-orientated towards the unravelled DNA. This indicates how changes to nucleosome structure can alter the way in which histone epitopes are presented.",2018-03-30,"Sundaramoorthy, R.; Hughes, A.; El-Mkami, H.; Norman, D.; Owen-Hughes, T.",,,,True
2d81bf103ad8ee0f0f3caf92fe2c523f0024691d,biorxiv,Receptor binding and proteolysis do not induce large conformational changes in the SARS-CoV spike,doi.org/10.1101/292672,,,See https://www.biorxiv.org/about-biorxiv,"Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 as a highly transmissible pathogenic human betacoronavirus. The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism. As SARS-CoV enters host cells, the viral S undergoes two proteolytic cleavages at S1/S2 and S2 sites necessary for efficient membrane fusion. Here, we present a cryo-EM analysis of the trimeric SARS-CoV S interactions with ACE2 and of the trypsin-cleaved S. Surprisingly, neither binding to ACE2 nor cleavage by trypsin at the S1/S2 cleavage site impart large conformational changes within S or expose the secondary cleavage site, S2. These observations suggest that S2 cleavage does not occur in the S prefusion conformation and that additional triggers may be required.",2018-03-31,"Kirchdoerfer, R. N.; Wang, N.; Pallesen, J.; Wrapp, D.; Turner, H. L.; Cotrell, C. A.; Corbett, K. S.; Graham, B. S.; McLellan, J. S.; Ward, A. B.",,,,False
ec6adb9dc121bcbb8215cb16b880d6dc6497d209,biorxiv,Isolation and sequencing of AGO-bound RNAs reveals characteristics of mammalian stem-loop processing in vivo,doi.org/10.1101/294488,,,See https://www.biorxiv.org/about-biorxiv,"MicroRNA precursors (pre-miRNAs) are short hairpin RNAs that are rapidly processed into mature microRNAs (miRNAs) in the cytoplasm. Due to their low abundance in cells, sequencing-based studies of pre-miRNAs have been limited. We successfully enriched for and deep sequenced pre-miRNAs in human cells by capturing these RNAs during their interaction with Argonaute (AGO) proteins. Using this approach, we detected > 350 pre-miRNAs in human cells and > 250 pre-miRNAs in a reanalysis of a similar study in mouse cells. We uncovered widespread trimming and non-templated additions to the 3 ends of pre- and mature miRNAs. Additionally, we created an index for microRNA precursor processing efficiency. This analysis revealed a subset of pre-miRNAs that produce low levels of mature miRNAs despite abundant precursors, including an annotated miRNA in the 5 UTR of the DiGeorge syndrome critical region 8 mRNA transcript. This led us to search for AGO-associated stem-loops originating from other mRNA species, which identified hundreds of putative pre-miRNAs derived from human and mouse mRNAs. In summary, we provide a wealth of information on mammalian pre-miRNAs, and identify novel microRNA and microRNA-like elements localized in mRNAs.",2018-04-06,"Silverman, I. M.; Gosai, S. J.; Vrettos, N.; Foley, S. W.; Berkowitz, N. D.; Mourelatos, Z.; Gregory, B. D.",,,,True
4eb8b7fd0032816e4a29d65b06939266d6446624,biorxiv,Encoding of odor fear memories in the mouse olfactory cortex,doi.org/10.1101/297226,,,See https://www.biorxiv.org/about-biorxiv,"Odor memories are exceptionally robust and essential for animal survival. The olfactory (piriform) cortex has long been hypothesized to encode odor memories, yet the cellular substrates for olfactory learning and memory remain unknown. Here, using intersectional, cFos-based genetic manipulations (\""Fos-tagging\""), we show that olfactory fear conditioning activates sparse and distributed ensembles of neurons in mouse piriform cortex. We demonstrate that chemogenetic silencing of these Fos-tagged piriform ensembles selectively interferes with odor fear memory retrieval, but does not compromise basic odor detection and discrimination. Furthermore, chemogenetic reactivation of piriform neurons that were Fos-tagged during olfactory fear conditioning causes a decrease in exploratory behavior, mimicking odor-evoked fear memory recall. Together, our experiments identify odor-specific ensembles of piriform neurons as necessary and sufficient for odor fear memory recall.",2018-04-07,"Meissner-Bernard, C.; Dembitskaya, Y.; Venance, L.; Fleischmann, A.",,,,True
b5e1d36298a78690140d5ccb9673dbd48a0ddcd3,biorxiv,The transcriptional and translational landscape of equine torovirus,doi.org/10.1101/296996,,,See https://www.biorxiv.org/about-biorxiv,"The genus Torovirus (subfamily Torovirinae, family Coronaviridae, order Nidovirales) encompasses a range of species that infect domestic ungulates including cattle, sheep, goats, pigs and horses, causing an acute self-limiting gastroenteritis. Using the prototype species equine torovirus (EToV) we performed parallel RNA sequencing (RNA-seq) and ribosome profiling (Ribo-seq) to analyse the relative expression levels of the known torovirus proteins and transcripts, chimaeric sequences produced via discontinuous RNA synthesis (a characteristic of the nidovirus replication cycle) and changes in host transcription and translation as a result of EToV infection. RNA sequencing confirmed that EToV utilises a unique combination of discontinuous and non-discontinuous RNA synthesis to produce its subgenomic RNAs; indeed, we identified transcripts arising from both mechanisms that would result in sgRNAs encoding the nucleocapsid. Our ribosome profiling analysis revealed that ribosomes efficiently translate two novel CUG-initiated ORFs, located within the so-called 5 UTR. We have termed the resulting proteins U1 and U2. Comparative genomic analysis confirmed that these ORFs are conserved across all available torovirus sequences and the inferred amino acid sequences are subject to purifying selection, indicating that U1 and U2 are functionally relevant. This study provides the first high-resolution analysis of transcription and translation in this neglected group of livestock pathogens.\n\nImportanceToroviruses infect cattle, goats, pigs and horses worldwide and can cause gastrointestinal disease. There is no treatment or vaccine and their ability to spill over into humans has not been assessed. These viruses are related to important human pathogens including severe acute respiratory syndrome (SARS) coronavirus and they share some common features, however the mechanism that they use to produce subgenomic RNA molecules differs. Here we performed deep sequencing to determine how equine torovirus produces subgenomic RNAs. In doing so, we also identified two previously unknown open reading frames \""hidden\"" within the genome. Together these results highlight the similarities and differences between this domestic animal virus and related pathogens of humans and livestock.",2018-04-07,"Stewart, H.; Brown, K.; Dinan, A. M.; Irigoyen, N.; Snijder, E. J.; Firth, A.",,,,True
eb5e5088c41f976387784acd57dbb683932c6002,biorxiv,The RZZ complex integrates spindle checkpoint maintenance with dynamic expansion of unattached kinetochores,doi.org/10.1101/297580,,,See https://www.biorxiv.org/about-biorxiv,"The Mad1-Mad2 heterodimer is the catalytic hub of the spindle assembly checkpoint (SAC), which controls mitosis through assembly of a multi-subunit anaphase inhibitor, the mitotic checkpoint complex (MCC) [1, 2]. Mad1-Mad2 first catalyzes MCC assembly at interphase nuclear pores [3], then migrates to kinetochores at nuclear envelope breakdown (NEBD) and resumes MCC assembly until bipolar spindle attachment is complete [1, 2]. There is significant debate about the factor(s) involved in targeting Mad1-Mad2 to kinetochores in higher eukaryotes [4-9]. Through gene editing and live-cell imaging, we found that the human Rod-Zw10-Zwilch (RZZ) complex is dispensable for cell viability and initial recruitment of Mad1-Mad2 to kinetochores at NEBD, but then becomes necessary to tether Mad1-Mad2 at kinetochores and sustain SAC arrest in cells challenged with spindle poisons. We also show that RZZ forms the mesh-like fibrous corona, a structural expansion of the outer kinetochore important for timely chromosome congression [10-13] once Mps1 phosphorylates the N-terminus of Rod. Artificially tethering Mad1-Mad2 to kinetochores enabled long-term mitotic arrest in the absence of RZZ. Conversely, blocking early RZZ-independent recruitment of Mad1-Mad2 eliminated the transient SAC response in RZZ-null cells. We conclude that RZZ drives structural changes in the outer kinetochore that facilitate chromosome bi-orientation and chronic SAC transduction, a key determinant of cytotoxicity during anti-mitotic drug therapy [14-16].",2018-04-09,"Rodriguez-Rodriguez, J.-A.; McKinley, K. L.; Sikirzhytski, V.; Corona, J.; Maciejowski, J.; Khodjakov, A.; Cheeseman, I. M.; Jallepalli, P.",,,,True
12c8ef5614d9a35bed3ff95a3b1dc971842514fe,biorxiv,A planarian nidovirus expands the limits of RNA genome size,doi.org/10.1101/299776,,,See https://www.biorxiv.org/about-biorxiv,"RNA viruses are the only known RNA-protein (RNP) entities capable of autonomous replication (albeit within a permissive environment). A 33.5-kb nidovirus has been considered close to the upper size limit for such entities; conversely, the minimal cellular DNA genome is ~200 kb. This large difference presents a daunting gap for the transition from primordial RNP to contemporary DNA-RNP-based life. Whether or not RNA viruses represent transitional steps on the road to DNA-based life, studies of larger RNA viruses advance our understanding of size constraints on RNP entities. For example, emergence of the largest previously known RNA genomes (20-34 kb in positive-stranded nidoviruses, including coronaviruses) is associated with a proofreading exoribonuclease encoded in the nidoviral open reading frame 1b (ORF1b). However, apparent constraints on the size of ORF1b, which encodes this and other key replicative enzymes, have been hypothesized to limit further expansion of viral RNA genomes. Here, we characterize a novel nidovirus (planarian secretory cell nidovirus; PSCNV) whose disproportionately large ORF1b-like region, and overall 41.1 kb genome, substantially extend the presumed limits on RNA genome size. This genome encodes a predicted 13,556-aa polyprotein in an unconventional single ORF, yet retains canonical nidoviral genome organization and expression, and key replicative domains. Our evolutionary analysis suggests that PSCNV diverged early from multi-ORF nidoviruses, and subsequently acquired additional genes, including those typical of large DNA viruses or hosts. PSCNVs greatly expanded genome, proteomic complexity, and unique features - impressive in themselves - attest to the likelihood of still-larger RNA genomes awaiting discovery.\n\nSignificance StatementRNA viruses are the only known RNA-protein (RNP) entities capable of autonomous replication. The upper genome size for such entities was assumed to be <35 kb; conversely, the minimal cellular DNA genome is ~200 kb. This large difference presents a daunting gap for the proposed evolution of contemporary DNA-RNP-based life from primordial RNP entities. Here, we describe a nidovirus from planarians, whose 41.1 kb genome is 23% larger than the largest known of RNA virus. The planarian secretory cell nidovirus has broken apparent constraints on the size of the genomic subregion that encodes core replication machinery, and has acquired genes not previously observed in RNA viruses. This virus challenges and advances our understanding of the limits to RNA genome size.",2018-04-11,"Saberi, A.; Gulyaeva, A. A.; Brubacher, J.; Newmark, P. A.; Gorbalenya, A.",,,,True
2238250b340cce482ba8dab2be98d10fcee965d4,biorxiv,IFITM proteins inhibit HIV-1 protein synthesis,doi.org/10.1101/201525,,,See https://www.biorxiv.org/about-biorxiv,"Interferon induced transmembrane proteins (IFITMs) inhibit the cellular entry of a broad range of viruses, but it has been suspected that for HIV-1 IFITMs may also inhibit a post-integration replicative step. We show that IFITM expression reduces HIV-1 viral protein synthesis by preferentially excluding viral mRNA transcripts from translation and thereby restricts viral production. Codon-optimization of proviral DNA rescues viral translation, implying that IFITM-mediated restriction requires recognition of viral RNA elements. In addition, we find that expression of the viral accessory protein Nef can help overcome the IFITM-mediated inhibition of virus production. Our studies identify a novel role for IFITMs in inhibiting HIV replication at the level of translation, but show that the effects can be overcome by the lentiviral protein Nef.",2018-04-11,"Lee, W. Y.; Liang, C.; Sloan, R.",,,,False
5502de277b6ee34f29d813cc49d7cda1168c202d,biorxiv,CHOP and IRE1α-XBP1/JNK signaling promote Newcastle Disease Virus induced apoptosis and benefit virus proliferation,doi.org/10.1101/300129,,,See https://www.biorxiv.org/about-biorxiv,"Newcastle disease virus (NDV) causes severe infectious disease in poultry, and selectively kills tumor cells by inducing apoptosis. In this report, we revealed the mechanisms underlying NDV-induced apoptosis via investigation of endoplasmic reticulum (ER) stress-related unfolded protein response (UPR) in HeLa cells. We found that NDV infection induced the expression of pro-apoptotic transcription factor CHOP via PKR-eIF2 pathway. Knock down and exogenous expression studies showed that CHOP promoted cell apoptosis by down-regulation of anti-apoptotic protein BCL-2 and MCL-1, promotion of pro-apoptotic JNK and p38 signaling, and suppression of pro-survival AKT signaling. Meanwhile, CHOP facilitated NDV proliferation. Furthermore, virus infection activated IRE1, another ER stress sensor, thereby promoting the mRNA splicing of XBP1 and resulting in the translation of transcription factor XBP1s. XBP1s entered into cell nucleus, promoted the expression of ER chaperones and components of ER associated degradation (ERAD). Exogenous expression of XBP1s helped IBV proliferation, and silence of XBP1s reduced virus proliferation. Meanwhile, exogenous expression and knock down studies demonstrated that IRE1 activated pro-apoptotic JNK signaling, promoted apoptosis and inflammation. In conclusion, our current study demonstrates that the induction of CHOP and activation of IRE1-XBP1/JNK signaling cascades promote apoptosis and benefit NDV proliferation.\n\nIMPORTANCEIt is well known that NDV kills host animal and tumor cells by inducing cell apoptosis. Although several studies investigate the apoptotic phenomena in NDV-infected tumor cells, the molecular mechanisms underlying this oncolytic virus induced apoptosis is not well understood yet. In this study, we focus on characterization of the ER stress responses in NDV-infected tumor cells, and find that virus induces apoptosis by up-regulation or activation of several unfolded protein responses (UPR) related transcription factors and signaling: such as ATF4, CHOP and XBP1s, and pro-apoptotic kinases (IRE1, JNK, p38). Moreover, activation of these transcription factors and signaling cascades helps virus proliferation. Our study dissects the UPR induced apoptosis in NDV-infected tumor cells, and provides the evidence that UPR favors NDV proliferation.",2018-04-12,"Li, Y.; Liao, Y.; Niu, Q.; Gu, F.; Sun, Y.; Meng, C.; Tan, L.; Song, C.; Qiu, X.; Ding, C.",,,,True
9af0b8e13e1e5ac714135dca8ba6d5216966066b,biorxiv,Evolved sequence features within the intrinsically disordered tail influence FtsZ assembly and bacterial cell division,doi.org/10.1101/301622,,,See https://www.biorxiv.org/about-biorxiv,"Intrinsically disordered regions (IDRs) challenge the well-established sequence-structure-function paradigm for describing protein function and evolution. Here, we direct a combination of biophysical and cellular studies to further our understanding of how the intrinsically disordered C-terminal tail of FtsZ contributes to cell division in rod-shaped bacteria. FtsZ is a modular protein that encompasses a conserved GTPase domain and a highly variable intrinsically disordered C-terminal tail (CTT). The CTT is essential for forming the cytokinetic Z-ring. Despite poor sequence conservation of the CTT, the patterning of oppositely charged residues, which refers to the extent of linear mixing / segregation of oppositely charged residues within CTT sequences is bounded within a narrow range. To assess the impact of evolutionary bounds on charge patterning within CTT sequences we performed experiments, aided by sequence design, to quantify the impact of changing the patterning of oppositely charged residues within the CTT on the functions of FtsZ from B. subtilis. Z-ring formation is robust if and only if the extent of linear mixing / segregation of oppositely charged residues within the CTT sequences is within evolutionarily observed bounds. Otherwise, aberrant, CTT-mediated, FtsZ assemblies impair Z-ring formation. The complexities of CTT sequences also have to be above a threshold value because FtsZ variants with low complexity CTTs are not tolerated in cells. Taken together, our results suggest that CTT sequences have evolved to be \""just right\"" and that this is achieved through an optimal extent of charge patterning while maintaining the sequence complexity above a threshold value.",2018-04-14,"Cohan, M. C.; Posey, A. E.; Grigsby, S. J.; Mittal, A.; Holehouse, A. S.; Buske, P. J.; Levin, P. A.; Pappu, R. V.",,,,True
c8559b6ddd6213bc91524397933bce33aea7d50f,biorxiv,Improving early epidemiological assessment of emerging Aedes-transmitted epidemics using historical data,doi.org/10.1101/300954,,,See https://www.biorxiv.org/about-biorxiv,"Model-based epidemiological assessment is useful to support decision-making at the beginning of an emerging Aedes-transmitted outbreak. However, early forecasts are generally unreliable as little information is available in the first few incidence data points. Here, we show how past Aedes-transmitted epidemics help improve these predictions. The approach was applied to the 2015-2017 Zika virus epidemics in three islands of the French West Indies, with historical data including other Aedes-transmitted diseases (Chikungunya and Zika) in the same and other locations. Hierarchical models were used to build informative a priori distributions on the reproduction ratio and the reporting rates. The accuracy and sharpness of forecasts improved substantially when these a priori distributions were used in models for prediction. For example, early forecasts of final epidemic size obtained without historical information were 3.3 times too high on average (range: 0.2 to 5.8) with respect to the eventual size, but were far closer (1.1 times the real value on average, range: 0.4 to 1.5) using information on past CHIKV epidemics in the same places. Likewise, the 97.5% upper bound for maximal incidence was 15.3 times (range: 2.0 to 63.1) the actual peak incidence, and became much sharper at 2.4 times (range: 1.3 to 3.9) the actual peak incidence with informative a priori distributions. Improvements were more limited for the date of peak incidence and the total duration of the epidemic. The framework can adapt to all forecasting models at the early stages of emerging Aedes-transmitted outbreaks.",2018-04-16,"Riou, J.; Poletto, C.; Boëlle, P.-Y.",,,,True
f905f78b32f63c6d14a79984dfb33f1b358b8ab4,biorxiv,Multimerization of HIV-1 integrase hinges on conserved SH3-docking platforms,doi.org/10.1101/301721,,,See https://www.biorxiv.org/about-biorxiv,"New anti-AIDS treatments must be continually developed in order to overcome resistance mutations including those emerging in the newest therapeutic target, the viral integrase (IN). Multimerization of IN is functionally imperative and provides a forthcoming therapeutic target. Allosteric inhibitors of IN bind to non-catalytic sites and prevent correct multimerization not only restricting viral integration but also the assembly and maturation of viral particles. Here, we report an allosteric inhibitor peptide targeting an unexploited SH3-docking platform of retroviral IN. The crystal structure of the peptide in complex with the HIV-1 IN core domain reveals a steric interference that would inhibit conserved docking of SH3-containing domain with the core domain vital for IN multimerization, providing a template for the development of novel anti-IN allosteric inhibitors.",2018-04-16,"Galilee, M.; Alian, A.",,,,True
37096cf81496ae9f053fefe062078a90feac754b,biorxiv,Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral divergence,doi.org/10.1101/302703,,,See https://www.biorxiv.org/about-biorxiv,"Molecular phylogenetics is often used to estimate the time since the divergence of modern gene sequences. For highly diverged sequences, such phylogenetic techniques sometimes estimate surprisingly recent divergence times. In the case of viruses, independent evidence indicates that the estimates of deep divergence times from molecular phylogenetics are sometimes too recent. This discrepancy is caused in part by inadequate models of purifying selection leading to branch-length underestimation. Here we examine the effect on branch-length estimation of using models that incorporate experimental measurements of purifying selection. We find that models informed by experimentally measured site-specific amino-acid preferences estimate longer deep branches on phylogenies of influenza virus hemagglutinin. This lengthening of branches is due to more realistic stationary states of the models, and is mostly independent of the branch-length-extension from modeling site-to-site variation in amino-acid substitution rate. The branch-length extension from experimentally informed site-specific models is similar to that achieved by other approaches that allow the stationary state to vary across sites. However, the improvements from all of these site-specific but time-homogeneous and site-independent models are limited by the fact that a proteins amino-acid preferences gradually shift as it evolves. Overall, our work underscores the importance of modeling site-specific amino-acid preferences when estimating deep divergence times--but also shows the inherent limitations of approaches that fail to account for how these preferences shift over time.",2018-04-17,"Hilton, S. K.; Bloom, J. D.",,,,False
3ddc987158400d3867939d3594da56dd546d6ddd,biorxiv,A novel framework for inferring parameters of transmission from viral sequence data,doi.org/10.1101/302331,,,See https://www.biorxiv.org/about-biorxiv,"Transmission between hosts is a critical part of the viral lifecycle. Recent studies of viral transmission have used genome sequence data to evaluate the number of particles transmitted between hosts, and the role of selection as it operates during the transmission process. However, the interpretation of sequence data describing transmission events is a challenging task. We here present a novel and comprehensive framework for using short-read sequence data to understand viral transmission events. Our model describes transmission as an event involving whole viruses, rather than independent alleles. We demonstrate how selection and noisy sequence data may each affect inferences of the population bottleneck, and identify circumstances in which selection for increased viral transmission may or may not be identified. Applying our model to data from a previous experimental transmission study, we show that our approach grants a more quantitative insight into viral transmission, inferring that between 2 to 6 viruses initiated infection, and allowing for a more informed interpretation of transmission events. While our model is here applied to influenza transmission, the framework we present is highly generalisable to other systems. Our work provides new opportunities for studying viral transmission.",2018-04-18,"Lumby, C. K.; Nene, N. R.; Illingworth, C. J. R.",,,,True
62298f90df017016d34e978befc29acbec201ccd,biorxiv,The alkyl side chain of PACA nanoparticles dictates the impact on cellular stress responses and the mode of particle-induced cell death,doi.org/10.1101/304618,,,See https://www.biorxiv.org/about-biorxiv,"For optimal exploitation of nanoparticles (NPs) in biomedicine, and to predict nanotoxicity, detailed knowledge on the cellular responses to cell-bound or internalized NPs is imperative. The outcome of NP-cell interaction is dictated by the type and magnitude of the NP insult and the cellular response. Here, we have systematically studied the impact of minor differences in NP composition on cellular stress responses and viability by using highly similar poly(alkylcyanoacrylate) (PACA) particles. Surprisingly, PACA particles differing only in their alkyl side chains; butyl (PBCA), ethylbutyl (PEBCA), or octyl (POCA), respectively, induced different stress responses and modes of cell death in human cell lines. POCA particles induced endoplasmic reticulum stress and apoptosis. In contrast, PBCA and PEBCA particles induced lipid peroxidation by depletion of the main cellular antioxidant glutathione (GSH), in a manner depending on the levels of the GSH precursor cystine, and transcription of the cystine transporter SLC7A11 regulated by ATF4 and Nrf2. Intriguingly, these particles activated the recently discovered cell death mechanism ferroptosis, which constitutes a promising alternative for targeting multidrug-resistant cancer stem-like cells. Of the two, PBCA was the strongest inducer. In summary, our findings highlight the cellular sensitivity to nanoparticle composition and have important implications for the choice of PACA monomer in therapeutical settings.",2018-04-19,"Szwed, M.; Soenstevold, T.; Oeverbye, A.; Engedal, N.; Grallert, B.; Moerch, Y. A.; Iversen, T.-G.; Skotland, T.; Sandvig, K.; Torgersen, M. L.",,,,True
e60640bfc445db0f53b5d92cb9f69cd943f1b73a,biorxiv,"Expanding the size limit of RNA viruses: Evidence of a novel divergent nidovirus in California sea hare, with a ~35.9 kb virus genome",doi.org/10.1101/307678,,,See https://www.biorxiv.org/about-biorxiv,"While RNA viruses thrive with massive structural and functional diversity, their genomes size variation is particularly low, ranging only from ~2-to-33 kb. Here, I present the characterization of RNA sequences corresponding to the first virus associated with Aplysia californica. Genome structure and domain architecture suggest that the identified virus is a novel member of Nidovirales. The proposed aplysia californica nido-like virus (AcNV), with a genome sequence of ca.35,906 nt, represents the longest ever recorded RNA virus yet. Phylogenetic insights indicate that AcNV clusters in a major phylloclade of unclassified invertebrate nidoviruses, Roniviridae, and Mesoniviridae. Basal branching in this emerging cluster could indicate that AcNV is a member of a novel divergent clade within Nidovirales. Further, virus RNA detection in multiple independent studies suggests that AcNV is neurotropic with a broad cell/tissue/organ tropism, supported by AcNV occurrence in diverse organs, including the first detection of a Nidovirales in single specific neurons.\n\nHighlights-RNA virus genomes reported in the literature are limited at ca. 33.4 kb\n-A novel nidovirus was identified in the gastropod mollusk Aplysia californica\n-The aplysia californica nido-like virus (AcNV) presents a 35.9 kb RNA genome\n-AcNV has a broad tropism, is enriched in the CNS, and accumulates in neurons\n-The unique features of A. californica enables single-neuron virus dynamics of AcNV",2018-04-24,"Debat, H. J.",,,,True
295036c0448244642eb6533de571def6cd8437e5,biorxiv,A speed-fidelity trade-off determines the mutation rate and virulence of an RNA virus,doi.org/10.1101/309880,,,See https://www.biorxiv.org/about-biorxiv,"Mutation rates can evolve through genetic drift, indirect selection due to genetic hitchhiking, or direct selection on the physicochemical cost of high fidelity. However, for many systems, it has been difficult to disentangle the relative impact of these forces empirically. In RNA viruses, an observed correlation between mutation rate and virulence has led many to argue that their extremely high mutation rates are advantageous, because they may allow for increased adaptability. This argument has profound implications, as it suggests that pathogenesis in many viral infections depends on rare or de novo mutations. Here we present data for an alternative model whereby RNA viruses evolve high mutation rates as a byproduct of selection for increased replicative speed. We find that a poliovirus antimutator, 3DG64S, has a significant replication defect and that wild type and 3DG64S populations have similar adaptability in two distinct cellular environments. Experimental evolution of 3DG64S under r-selection led to reversion and compensation of the fidelity phenotype. Mice infected with 3DG64S exhibited delayed morbidity at doses well above the LD50, consistent with attenuation by slower growth as opposed to reduced mutational supply. Furthermore, compensation of the 3DG64S growth defect restored virulence, while compensation of the fidelity phenotype did not. Our data are consistent with the kinetic proofreading model for biosynthetic reactions and suggest that speed is more important than accuracy. In contrast to what has been suggested for many RNA viruses, we find that within host spread is associated with viral replicative speed and not standing genetic diversity.\n\nAuthor SummaryMutation rate evolution has long been a fundamental problem in evolutionary biology. The polymerases of RNA viruses generally lack proofreading activity and exhibit extremely high mutation rates. Since most mutations are deleterious and mutation rates are tuned by natural selection, we asked why hasnt the virus evolved to have a lower mutation rate? We used experimental evolution and a murine infection model to show that RNA virus mutation rates may actually be too high and are not necessarily adaptive. Rather, our data indicate that viral mutation rates are driven higher as a result of selection for viruses with faster replication kinetics. We suggest that viruses have high mutation rates, not because they facilitate adaption, but because it is hard to be both fast and accurate.",2018-04-27,"Fitzsimmons, W.; Woods, R. J.; McCrone, J. T.; Woodman, A.; Arnold, J. J.; Yennawar, M.; Evans, R.; Cameron, C. E.; Lauring, A. S.",,,,True
2da0a7ba851e53d21dba05042a397eafcdab093d,biorxiv,Combination attenuation offers strategy for live-attenuated coronavirus vaccines,doi.org/10.1101/309591,,,See https://www.biorxiv.org/about-biorxiv,"With an ongoing threat posed by circulating zoonotic strains, new strategies are required to prepare for the next emergent coronavirus (CoV). Previously, groups had targeted conserved coronavirus proteins as a strategy to generate live-attenuated vaccine strains against current and future CoVs. With this in mind, we explored whether manipulation of CoV NSP16, a conserved 2O methyltransferase (MTase), could provide a broad attenuation platform against future emergent strains. Using the SARS-CoV mouse model, a NSP16 mutant vaccine was evaluated for protection from heterologous challenge, efficacy in the aging host, and potential for reversion to pathogenesis. Despite some success, concerns for virulence in the aged and potential for reversion makes targeting NSP16 alone an untenable approach. However, combining a 2O MTase mutation with a previously described CoV fidelity mutant produced a vaccine strain capable of protection from heterologous virus challenge, efficacy in aged mice, and no evidence for reversion. Together, the results indicate that targeting the CoV 2O MTase in parallel with other conserved attenuating mutations may provide a platform strategy for rapidly generating live-attenuated coronavirus vaccines.\n\nSignificanceEmergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed to stem future outbreaks. However, failure of many previous CoV vaccine formulations has clearly highlighted the need to test efficacy under different conditions and especially in vulnerable populations like the aged and immune-compromised. This study illustrates that despite success in young models, the NSP16 mutant carries too much risk for pathogenesis and reversion in vulnerable models to be used as a stand-alone vaccine strategy. Importantly, the NSP16 mutation can be paired with other attenuating approaches to provide robust protection from heterologous challenge and in vulnerable populations. Coupled with increased safety and reduced pathogenesis, the study highlights the potential for NSP16 attenuation as a major component of future live-attenuated coronavirus vaccines.",2018-04-28,"Menachery, V. D.; Gralinski, L.; Mitchell, H. D.; Dinnon, K.; Leist, S. R.; Yount, B.; McAnarney, E. T.; Graham, R.; Waters, K. M.; Baric, R. S.",,,,True
d49ace1927b3f15077e16db028f0b440f60e222e,biorxiv,Genome Sequence of Indian Peacock Reveals the Peculiar Case of a Glittering Bird,doi.org/10.1101/315457,,,See https://www.biorxiv.org/about-biorxiv,"The unique ornamental features and extreme sexual traits of Peacock have always intrigued the scientists. However, the genomic evidence to explain its phenotype are yet unknown. Thus, we report the first genome sequence and comparative analysis of peacock with the available high-quality genomes of chicken, turkey, duck, flycatcher and zebra finch. The candidate genes involved in early developmental pathways including TGF-{beta}, BMP, and Wnt signaling pathway, which are also involved in feather patterning, bone morphogenesis, and skeletal muscle development, showed signs of adaptive evolution and provided useful clues on the phenotype of peacock. The innate and adaptive immune components such as complement system and T-cell response also showed signs of adaptive evolution in peacock suggesting their possible role in building a robust immune system which is consistent with the between species predictions of Hamilton-Zuk hypothesis. This study provides novel genomic and evolutionary insights into the molecular understanding towards the phenotypic evolution of Indian peacock.",2018-05-05,"Jaiswal, S. K.; Gupta, A.; Saxena, R.; Prasoodanan, V. P. K.; Sharma, A. K.; Mittal, P.; Roy, A.; Shafer, A. B. A.; Vijay, N.; Sharma, V. K.",,,,False
64b327001f8fa95b83dc23259a2ad617be12498c,biorxiv,HIV-1 Protease Evolvability is Affected by Synonymous Nucleotide Recoding,doi.org/10.1101/315366,,,See https://www.biorxiv.org/about-biorxiv,"One unexplored aspect of HIV-1 genetic architecture is how codon choice influences population diversity and evolvability. Here we compared the development of HIV-1 resistance to protease inhibitors (PIs) between wild-type (WT) virus and a synthetic virus (MAX) carrying a codon-pair re-engineered protease sequence including 38 (13%) synonymous mutations. WT and MAX viruses showed indistinguishable replication in MT-4 cells or PBMCs. Both viruses were subjected to serial passages in MT-4 cells with selective pressure from the PIs atazanavir (ATV) and darunavir (DRV). After 32 successive passages, both the WT and MAX viruses developed phenotypic resistance to PIs (IC50 14.6 {+/-} 5.3 and 21.2 {+/-} 9 nM for ATV, and 5. 9 {+/-} 1.0 and 9.3 {+/-} 1.9 for DRV, respectively). Ultra-deep sequence clonal analysis revealed that both viruses harbored previously described resistance mutations to ATV and DRV. However, the WT and MAX virus proteases showed different resistance variant repertoires, with the G16E and V77I substitutions observed only in WT, and the L33F, S37P, G48L, Q58E/K, and L89I substitutions detected only in MAX. Remarkably, G48L and L89I are rarely found in vivo in PI-treated patients. The MAX virus showed significantly higher nucleotide and amino acid diversity of the propagated viruses with and without PIs (P < 0.0001), suggesting higher selective pressure for change in this recoded virus. Our results indicate that HIV-1 protease position in sequence space delineates the evolution of its mutant spectra. Nevertheless, the investigated synonymously recoded variant showed mutational robustness and evolvability similar to the WT virus.\n\nIMPORTANCELarge-scale synonymous recoding of virus genomes is a new tool for exploring various aspects of virus biology. Synonymous virus genome recoding can be used to investigate how a viruss position in sequence space defines its mutant spectrum, evolutionary trajectory, and pathogenesis. In this study, we evaluated how synonymous recoding of the human immunodeficiency virus type 1 (HIV-1) protease impacts the development of protease inhibitor (PI) resistance. HIV-1 protease is a main target of current antiretroviral therapies. Our present results demonstrate that the wild-type (WT) virus and the virus with the recoded protease exhibited different patterns of resistance mutations after PI treatment. Nevertheless, the developed PI resistance phenotype was indistinguishable between the recoded virus and the WT virus, suggesting that the synonymously recoded protease HIV-1 and the WT protease virus were equally robust and evolvable.",2018-05-07,"Nevot, M.; Jordan-Paiz, A.; Martrus, G.; Andres, C.; Garcia-Cehic, D.; Gregori, J.; Franco, S.; Quer, J.; Martinez, M. A.",,,,True
532dc582abd41e833303742ca40976db63fe6fc1,biorxiv,Site specific target binding controls RNA cleavage efficiency by the Kaposi’s sarcoma-associated herpesvirus endonuclease SOX,doi.org/10.1101/320929,,,See https://www.biorxiv.org/about-biorxiv,"During lytic replication of Kaposis sarcoma-associated herpesvirus (KSHV), the gene expression landscape of a cell is remodeled to evade the immune response and create an environment favorable to viral replication. A major driver of these gene expression changes is a virally encoded, messenger RNA (mRNA)-specific endonuclease termed SOX. SOX cleaves the majority of cytoplasmic mRNAs, but does so at specific internal sites loosely defined by a degenerate sequence motif. If and how RNA sequence directs SOX targeting remained unknown. To address these questions, we used recombinant, highly purified SOX endonuclease in a series of biochemical assays to reconstitute the cleavage reaction in vitro and gain significant insight into the biochemical mechanism of both SOX target recognition and endonucleolytic cleavage. Using this system, we determined that cut site specificity is preserved with purified SOX and a validated target RNA and thus does not require additional cellular cofactors. Furthermore, we showed that SOX displays robust, sequence-specific RNA binding to residues proximal to the cleavage site, which must be presented in a particular structural context. The strength of SOX binding dictates cleavage efficiency, providing an explanation for the breadth of target RNA susceptibility observed in cells.\n\nSignificance StatementKaposis sarcoma-associated herpesvirus (KSHV) is an oncogenic human virus that causes Kaposis sarcoma, primary effusion lymphoma, and multicentric Castleman disease. During viral replication, KSHV expresses an enzyme called SOX that cuts and inactivates the majority of cellular messenger RNAs, preventing their translation into proteins. Some mRNAs are efficiently cleaved by SOX, while others are poorly cleaved, but the mechanistic basis underlying this selectivity has remained largely unknown. Here, we reveal that the efficiency of RNA cleavage is heavily impacted by RNA sequences proximal to the cleavage site, which serve as a SOX binding platform. This helps explain both the range of RNA cleavage efficiency observed in SOX-expressing cells as well as the sequence specificity underlying SOX targeting.",2018-05-13,"Mendez, A. S.; Vogt, C.; Bohne, J.; Glaunsinger, B. A.",,,,True
58be9171c1a62b6102eab7c4bbd364d11c14ff5a,biorxiv,A functional different immune capacity in cattle is associated with higher mastitis incidence,doi.org/10.1101/311316,,,See https://www.biorxiv.org/about-biorxiv,"Bovine neonatal pancytopenia (BNP) was a deadly disease transferred by antibodies from 5-10% of cows given a novel BVD vaccine. Disease was lethal in 90% of calves receiving colostrum with BNP antibodies. The cause of BNP is not fully understood to date. We revealed a profound difference in immune capacities between BNP dams and non-responders. Significant differences were detectable in response to in vitro stimulation of peripheral blood derived lymphocytes to several mitogens and IL-2. BNP cows regulated their immune proteomes completely different from controls with other immune response master regulators. Since we detected this response pattern also in 22% of cows that were never vaccinated at all, this immune deviant (ID) phenotype is still present in cattle and probably inherited. Immune response pattern of these cows was stable over an observation period of 38 months. Importantly, ID have a significant increased prevalence of mastitis underscoring the clinical importance.",2018-05-14,"Lutterberg, K.; Kleinwort, K. J. H.; Hobmaier, B. F.; Hauck, S. M.; Nueske, S.; Scholz, A. M.; Deeg, C. A.",,,,False
ff6bd29c8ecd325c4edddb2b050d5f4919db6112,biorxiv,Deep sequencing of primary human lung epithelial cells challenged with H5N1 influenza virus reveals a proviral role for CEACAM1,doi.org/10.1101/324723,,,See https://www.biorxiv.org/about-biorxiv,"Current prophylactic and therapeutic strategies targeting human influenza viruses include vaccines and antivirals. Given variable rates of vaccine efficacy and antiviral resistance, alternative strategies are urgently required to improve disease outcomes. Here we describe the use of HiSeq deep sequencing to analyze host gene expression in primary human alveolar epithelial type II cells infected with highly pathogenic avian influenza H5N1 virus. At 24 hours post-infection, 623 host genes were significantly up-regulated, including the cell adhesion molecule CEACAM1. The up-regulation of CEACAM1 was blocked in the presence of the reactive oxygen species inhibitor, apocynin. H5N1 virus infection stimulated significantly higher CEACAM1 protein expression when compared to low pathogenic PR8 H1N1 virus, suggesting a key role for CEACAM1 in influenza virus pathogenicity. Furthermore, silencing of endogenous CEACAM1 resulted in reduced levels of proinflammatory cytokine/chemokine production, as well as reduced levels of virus replication following H5N1 infection. Our study provides evidence for the involvement of CEACAM1 in a clinically relevant model of H5N1 infection and may assist in the development of host-oriented antiviral strategies.",2018-05-17,"Ye, S.; Cowled, C. J.; Yap, C.-H.; Stambas, J.",,,,True
ea94779ce166bcbf3813ccaab028524ff397089b,biorxiv,Messenger RNAs transcribed from yeast linear cytoplasmic plasmids possess unconventional 5’ and 3’ UTRs and suggest a novel mechanism of translation,doi.org/10.1101/325316,,,See https://www.biorxiv.org/about-biorxiv,"Linear plasmids with almost identical compact genetic organization have been found in the cytoplasm of yeast species from nine genera. We employed pGKL1,2 plasmids from Kluyveromyces lactis as a model to investigate the previously unstudied transcriptome of yeast cytoplasmic linear plasmids. We performed 5 and 3 RACE analysis of all the pGKL1,2 mRNAs and found them not 3 polyadenylated and containing mostly uncapped 5 poly(A) leaders that are not complementary to the plasmid DNA. The degree of 5 capping and/or 5 polyadenylation is specific to each gene and is controlled by the corresponding promoter regions. We refined the description of the pGKL1,2 promoters and found new alternative promoters of several genes. We also provide evidence that K2ORF3 encodes an mRNA cap guanine-N7-methyltransferase and that 5 capped pGKL1,2 transcripts contain N7-methylated caps. Translation of pGKL1,2 transcripts is enhanced in Ism1{Delta} and pab1{Delta} strains and is independent of eIF4E and Pab1 translation factors. We suggested a model of a primitive regulation of pGKL1,2 plasmids gene expression where degree of 5 mRNA capping, degree of 5 non-template polyadenylation and presence of negative regulators as PAB1 and Lsm1 play an important role. Our data also suggest a close relationship between linear plasmids and poxviruses.",2018-05-17,"Vopalensky, V.; Sykora, M.; Masek, T.; Pospisek, M.",,,,True
317215c463463ddb39fa7564f67239dc484b86a9,biorxiv,Projecting the end of the Zika virus epidemic in Latin America: a modelling analysis,doi.org/10.1101/323915,,,See https://www.biorxiv.org/about-biorxiv,"Background Zika virus (ZIKV) emerged in Latin America & the Caribbean (LAC) region in 2013, and has had serious implications for population health in the region. In 2016, the World Health Organization declared the ZIKV outbreak a Public Health Emergency of International Concern following a cluster of associated neurological disorders and neonatal malformations. In 2017, Zika cases declined, but future incidence in LAC remains uncertain due to gaps in our understanding, considerable variation in surveillance and a lack of a comprehensive collation of data from affected countries.\n\nMethods Our analysis combines information on confirmed and suspected Zika cases across LAC countries and a spatio-temporal dynamic transmission model for ZIKV infection to determine key transmission parameters and projected incidence in 91 major cities within 35 countries. Seasonality was determined by spatio-temporal estimates of Aedes aegypti vector capacity. We used country and state-level data from 2015 to mid-2017 to infer key model parameters, country-specific disease reporting rates, and the 2018 projected incidence. A 10-fold cross-validation approach was used to validate parameter estimates to out-of-sample epidemic trajectories.\n\nResults There was limited transmission in 2015, but in 2016 and 2017 there was sufficient opportunity for wide-spread ZIKV transmission in most cities, resulting in the depletion of susceptible individuals. We predict that the highest number of cases in 2018 within some Brazilian States (Sao Paulo and Rio de Janeiro), Colombia and French Guiana, but the estimated number of cases were no more than a few hundred. Model estimates of the timing of the peak in incidence were correlated (p<0.05) with the reported peak in incidence. The reporting rate varied across countries, with lower reporting rates for those with only confirmed cases compared to those who reported both confirmed and suspected cases.\n\nConclusions The findings suggest that the ZIKV epidemic is by and large over, with incidence projected to be low in most cities in LAC in 2018. Local low levels of transmission are probable but the estimated rate of infection suggests that most cities have a population with high levels of herd immunity.",2018-05-18,"O'Reilly, K.; Lowe, R.; Edmunds, J.; Mayaud, P.; Kucharski, A.; Eggo, R. M.; Funk, S.; Bhatia, D.; Khan, K.; Kramer, M.; Wilder-Smith, A.; Rodrigues, L.; Brasil, P.; Massad, E.; Jaenisch, T.; Cauchemez, S.; Brady, O.; Yakob, L.",,,,True
f32841f22efe8c2bccd0d04a0c0b47e6ecf86b61,biorxiv,Attenuation of influenza A virus disease severity by viral co-infection in a mouse model,doi.org/10.1101/326546,,,See https://www.biorxiv.org/about-biorxiv,"Influenza viruses and rhinoviruses are responsible for a large number of acute respiratory viral infections in human populations and are detected as co-pathogens within hosts. Clinical and epidemiological studies suggest that co-infection by rhinovirus and influenza virus may reduce disease severity and that they may also interfere with each others spread within a host population. To determine how co-infection by these two unrelated respiratory viruses affects pathogenesis, we established a mouse model using a minor serogroup rhinovirus (RV1B) and mouse-adapted influenza A virus (PR8). Infection of mice with RV1B two days before PR8 reduced pathogenesis of mild to moderate, but not severe PR8 infections. Disease attenuation was associated with an early inflammatory response in the lungs and enhanced clearance of PR8. However, co-infection by RV1B did not reduce PR8 viral loads early in infection or inhibit replication of PR8 within respiratory epithelia or in vitro. Inflammation in co-infected mice remained focal, in comparison to diffuse inflammation and damage in the lungs of mice infected by PR8. These findings suggest that RV1B stimulates an early immune response that clears PR8 while limiting excessive pulmonary inflammation. The timing of RV1B co-infection was a critical determinant of protection, suggesting that sufficient time is needed to induce this response. Finally, disease attenuation was not unique to RV1B: co-infection by a murine coronavirus two days before PR8 also reduced disease severity. This model will be critical for understanding the mechanisms responsible for attenuation of influenza disease during co-infection by unrelated respiratory viruses.",2018-05-19,"Gonzalez, A. J.; Ijezie, E. C.; Balemba, O. B.; Miura, T. A.",,,,True
10abb3e977aa476a39bce4f1feda37c2e1250106,biorxiv,Replication of MERS and SARS coronaviruses in bat cells offers insights to their ancestral origins,doi.org/10.1101/326538,,,See https://www.biorxiv.org/about-biorxiv,"Previous findings of Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses in bats, and the ability of Tylonycteris-BatCoV HKU4 spike protein to utilize MERS-CoV receptor, human dipeptidyl peptidase 4 hDPP4, suggest a bat ancestral origin of MERS-CoV. We developed 12 primary bat cell lines from seven bat species, including Tylonycteris pachypus, Pipistrellus abramus and Rhinolophus sinicus (hosts of Tylonycteris-BatCoV HKU4, Pipistrellus-BatCoV HKU5 and SARS-related-CoV respectively), and tested their susceptibilities to MERS-CoVs, SARS-CoV and human coronavirus 229E (HCoV-229E). Five cell lines, including P. abramus and R. sinicus but not T. pachypus cells, were susceptible to human MERS-CoV EMC/2012. However, three tested camel MERS-CoV strains showed different infectivities, with only two strains capable of infecting three and one cell lines respectively. SARS-CoV can only replicate in R. sinicus cells, while HCoV-229E cannot replicate in any bat cells. Bat dipeptidyl peptidase 4 (DPP4) sequences were closely related to those of human and non-human primates but distinct from dromedary DPP4 sequence. Critical residues for binding to MERS-CoV spike protein were mostly conserved in bat DPP4. DPP4 was expressed in the five bat cells susceptible to MERS-CoV, with significantly higher mRNA expression levels than those in non-susceptible cells (P=0.0174), supporting that DPP4 expression is critical for MERS-CoV infection in bats. However, overexpression of T. pachypus DPP4 failed to confer MERS-CoV susceptibility in T. pachypus cells, suggesting other cellular factors in determining viral replication. The broad cellular tropism of MERS-CoV should prompt further exploration of host diversity of related viruses to identify its ancestral origin.",2018-05-20,"Lau, S.; Fan, R. Y.; Luk, H. K. H.; Zhu, L.; Fung, J.; Li, K. S.; Wong, E. Y. M.; Ahmed, S. S.; Chan, J. F. W.; Kok, K.-H.; Chan, K.-H.; Wernery, U.; Yuen, K.-y.; Woo, P. C. Y.",,,,True
1a9c229f4f866db4f9c23a77b8c1275b52407c64,biorxiv,Early in planta detection of Xanthomonas axonopodis pv. punicae in pomegranate using enhanced loop-mediated isothermal amplification assay,doi.org/10.1101/328674,,,See https://www.biorxiv.org/about-biorxiv,"Bacterial blight in pomegranate caused by Xanthomonas axonopodis pv. punicae (Xap) is an increasing threat for pomegranate cultivation in India. To prevent the economic losses, it is pivotal to detect the infection in latent stages rather than in later stages. We have developed an enhanced method termed as loop-mediated isothermal amplification (LAMP) technique to evaluate for the latent detection of Xap in pomegranate using six set of specific primers. Three DNA intercalating dyes were used, such as Ethidium bromide, hydroxynaphthol blue (HNB) and SYBR Green resulted in visualising the positivity for LAMP assay. The reaction time and temperature were to be 65{degrees}C from 30 min onwards, for the dyes and its sensitivity was observed up to 10-7 ng in the LAMP assay. For field applicability, LAMP assay detected Xap on 7th day post infection while the PCR amplified Xap after 11th day post infection. Finally, the specificity of LAMP assay was validated to be positive with ten Xap isolates for its accuracy and 29 non-Xap bacterial isolates showed negative results. Moreover, this method could be used as a better alternative to PCR based methods, for early detection of the pathogens.",2018-05-22,"Prasanna Kumar, M. K.; Parivallal, P. B.; Manjunath, C.; Mahesh, H.; Narayan, K. S.; babu, g. v.; priyanka, K.; Puneeth, M. E.; Rangaswamy, K. T.",,,,True
23f1bab7d94bd0564e2319fddf75c1c7987ce75f,biorxiv,Complex dynamics in an SIS epidemic model induced by nonlinear incidence,doi.org/10.1101/331678,,,See https://www.biorxiv.org/about-biorxiv,"We study an epidemic model with nonlinear incidence rate, describing the saturated mass action as well as the psychological effect of certain serious diseases on the community. Firstly, the existence and local stability of disease-free and endemic equilibria are investigated. Then, we prove the occurrence of backward bifurcation, saddle-node bifurcation, Hopf bifurcation and cusp type Bogdanov-Takens bifurcation of codimension 3. Finally, numerical simulations, including one limit cycle, two limit cycles, unstable homoclinic loop and many other phase portraits are presented. These results show that the psychological effect of diseases and the behavior change of the susceptible individuals may affect the final spread level of an epidemic.",2018-05-25,"Yuan, R.; Teng, Z.; Li, J.",,,,True
4e3f4e31c370281c2d721d6113265c25d9c566c5,biorxiv,Host protein CD63 enhances viral RNA replication by interacting with human astrovirus nonstructural protein nsP1a/4,doi.org/10.1101/331835,,,See https://www.biorxiv.org/about-biorxiv,"Human astrovirus nonstructural protein nsP1a/4, located at the C-terminal end of nsP1a, is thought to be involved in the regulation of RNA replication and capsid maturation;however, its rolesviral growth and virulence are not well understood. We investigated the intracellular host proteins that interact with nsP1a and explored the potential roles of the interaction in the pathogenesis of human astrovirus infection. We screened 14 independent proteins with a cDNA library derived from Caco-2 cells using a yeast two-hybrid technique. Deletion analysis revealed that interaction between the nsP1a/4 domain and the large extracellular loop (LEL) domain of the human protein CD63 is necessary for astrovirus replication. The interaction was confirmed by glutathione-S-transferase (GST) pull-down assays and co-immunoprecipitation assays. Confocal microscopy showed that nsP1a/4 and CD63 co-localized in the cytoplasm of infected cells. Over expression of CD63 promoted viral RNA synthesis, whereas knockdown of CD63 markedly decreased viral RNA levels. Those results suggest that CD63 plays a critical role in human astrovirus RNA replication. The interaction between CD63 and nsP1a/4 provides a channel to further understand the roles of interactions between host and virus proteins in astrovirus infection and release.\n\nIMPORTANCEHuman astroviruses cause gastroenteritis in young children and immunocompromised patients. In this study, we provide evidence that nsP1a/4, a nonstructural protein located at the C-terminal end of the human astrovirus nsP1a polyprotein, interacts with the host protein CD63. Over expression of CD63 promoted viral RNA replication, whereas knockdown of CD63 decreased virus RNA replication, indicating that CD63 plays a critical role in the human astrovirus life cycle.",2018-05-27,"zhao, w.; liu, N.; Tao, X. L.; Zheng, C. h.; Li, X. y.; Yu, M.; Li, Y. g.",,,,True
4a24fcf8d2a7c69aef247ea12a740145daf68407,biorxiv,Deconvoluting Virome-Wide Antiviral Antibody Profiling Data,doi.org/10.1101/333625,,,See https://www.biorxiv.org/about-biorxiv,"The ability to comprehensively characterize exposures and immune responses to viral infections will be critical to better understanding human health and disease. We previously described the VirScan system, a phage-display based technology for profiling antibody binding to a comprehensive library of peptides designed to represent the human virome. The previous VirScan analytical approach did not fully account for disproportionate representation of viruses in the library or for antibody cross-reactivity among sequences shared by related viruses. Here we present the  AntiViral Antibody Response Deconvolution Algorithm ( AVARDA), a multi-module software package for analyzing VirScan datasets. AVARDA provides a probabilistic assessment of infection at species-level resolution by considering alignment of all library peptides to each other and to all human viruses. We employed AVARDA to analyze VirScan data from a cohort of encephalitis patients with either known viral infections or undiagnosed etiologies. By comparing acute and convalescent sera, AVARDA successfully confirmed or detected antibody responses to human herpesviruses 1, 3, 4, 5, and 6, thereby improving the rate of diagnosing viral encephalitis in this cohort by 62.5%. We further assessed AVARDAs utility in the setting of an epidemiological study, demonstrating its ability to determine infections acquired in a child followed prospectively from infancy. We consider ways in which AVARDAs conceptual framework may be further developed in the future and describe how its analyses may be extended beyond investigations of viral infection. AVARDA, in combination with VirScan and other pan-pathogen serological techniques, is likely to find broad utility in the epidemiology and diagnosis of infectious diseases.",2018-05-30,"Monaco, D.; Kottapalli, S.; Yuan, T.; Breitwieser, F.; Anderson, D.; Wijaya, L.; Tan, K.; Chia, W. N.; Kammers, K.; Caturegli, M.; Waugh, K.; Rewers, M.; Wang, L.-F.; Larman, H.",,,,True
d47377d0da60ea7aab2522c204ad65753b0545fe,biorxiv,"Genotypic diversity, circulation patterns, and co-detections among rhinoviruses in Queensland, 2001",doi.org/10.1101/334334,,,See https://www.biorxiv.org/about-biorxiv,"Rhinoviruses (RVs) occur more frequently than other viruses and more often in people displaying symptoms than in those without. RVs exacerbate chronic airway disease and confound the clinical diagnosis of influenza-like illness. We sought to estimate the spectrum of RV diversity, RV species seasonality and to breakdown RV involvement in respiratory virus co-detections by comprehensive molecular testing of a convenience collection of airway sample extracts from patients with suspected respiratory infections, collected during 2001.\n\nRVs were the most common virus detected. We were able to genotype [~]90% of RV detections, identifying 70 distinct RVs, spanning all three species. RV-Bs were under-represented. We found RV species co-circulated at times, although one species usually dominated. Each species displayed a bimodal distribution.\n\nNotably, RVs and influenza A viruses (IFAV) seldom co-occurred, supporting their roles as primary pathogens of the airway among acutely ill infants. Whether RV circulation has a moderating or controlling effect on the IFAV season or is controlled by it cannot be determined from these data.\n\nDespite the frequent perception that RVs commonly co-occur with another virus, our findings indicated this was not the case. Nearly 80% of RV detections occurred alone. Understanding more about population-level interference between viruses may allow us to harness aspects of it to generate a non-specific antiviral intervention that mimics a putative protective effect.\n\nFor routine respiratory virus screening to best serve the patient, RV testing should be a principal component of any acute respiratory illness testing algorithm throughout the year.",2018-05-30,"Arden, K. E.; Greer, R. M.; Wang, C. Y.; Mackay, I. M.",,,,True
e8b2e667f2145ec96fbb6400fb41b05cafa26e37,biorxiv,Evaluation of the cytotoxic potential of extracts from the genus Passiflora cultived in Brazil against cancer cells,doi.org/10.1101/337253,,,See https://www.biorxiv.org/about-biorxiv,"This work aimed to evaluate the cytotoxic potential against cancer cells of Passiflora genus plant species cultivated in Brazil and identify the mechanism of cytotoxicity induced by the most promising extract. Leaf extracts from 14 Passiflora (P.) species were obtained ASE and in vitro cytotoxicity evaluated against cancer cell lines using MTT assay at a single concentration of 50 g/mL. Additionally, the IC50 of the P. alata (ELPA) leaf extracts was determined against both tumor (HCT-116, SF-295, OVACAR-8, and HL-60), and non-tumor cells (PBMC). The ELPA flavonoids were identified by HPLC-DAD and UHPLC-MS/MS. The morphological analyses used light and fluorescence microscopy, and cell cycle and DNA fragmentation analyses used flow cytometry to determine the mechanism of cell death induced by ELPA in HL-60. Among the Passiflora leaf extracts evaluated; ELPA stood out with high cytotoxic activity, followed by P. capsularis and P. quadrangulares with varying high and low cytotoxic activity. ELPA presented high cytotoxic potency in HL-60 (IC50 19.37 g/mL), yet without cytotoxic activity against PBMC, suggesting selectivity for tumor cells. The cytotoxic activity of ELPA may well be linked to the presence of ten identified flavonoids. Cells treated with ELPA presented the hallmarks typical of apoptosis and necrosis, with cell cycle arrest in the G2/M phase. Conclusion: From among the studied species, ELPA presented greater cytotoxic activity, possibly a consequence of synergistic flavonoid action which induces cell death by apoptosis and necrosis.",2018-06-01,"Amaral, R. G.; Gomes, S. V. F.; Antoniolli, A. R.; Luciano, M. C. d. S.; Pessoa, C. d. O.; Andrade, L. N.; Severino, P. N.; Brandao, G. C.; Bomfim, L. M.; Bezerra, D. P.; David, J. M.; Carvalho, A. A.",,,,True
9cfdce851951c817101b36f7b292e744906474c4,biorxiv,Rapid Therapeutic Recommendations in the Context of a Global Public Health Crisis using Translational Bioinformatics Approaches: A proof-of-concept study using Nipah Virus Infection,doi.org/10.1101/333021,,,See https://www.biorxiv.org/about-biorxiv,"We live in a world of emerging new diseases and old diseases resurging in more aggressive forms. Drug development by pharmaceutical companies is a market-driven and costly endeavor, and thus it is often a challenge when drugs are needed for diseases endemic only to certain regions or which affect only a few patients. However, biomedical open data is accessible and reusable for reanalysis and generation of a new hypotheses and discovery. In this study, we leverage biomedical data and tools to analyze available data on Nipah Virus (NiV) infection. NiV infection is an emerging zoonosis that is transmissible to humans and is associated with high mortality rates. In this study, explored the application of computational drug repositioning and chemogenomic enrichment analyses using host transcriptome data to match drugs that could reverse the virus-induced gene signature. We performed analyses using two gene signatures: i) A previously published gene signature (n=34), and ii) a gene signature generated using the characteristic direction method (n= 5,533). Our predictive framework suggests that several drugs including FDA approved therapies like beclometasone, trihexyphenidyl, S-propranolol etc. could modulate the NiV infection induced gene signatures in endothelial cells. A target specific analysis of CXCL10 also suggests the potential application of Eldelumab, an investigative therapy for Crohns disease and ulcerative colitis, as a putative candidate for drug repositioning. To conclude, we also discuss challenges and opportunities in clinical trials (n-of-1 and adaptive trials) for repositioned drugs. Further follow-up studies including biochemical assays and clinical trials are required to identify effective therapies for clinical use. Our proof-of-concept study highlights that translational bioinformatics methods including gene expression analyses and computational drug repositioning could augment epidemiological investigations in the context of an emerging disease with no effective treatment.",2018-06-04,"Shameer, K.; Johnson, K. W.; Readhead, B.; Glicksberg, B.; McCallum, C.; R, A.; Hirsch, J.; Bock, K.; Chelico, J.; Hajizadeh, N.; Oppenheim, M.; Dudley, J.",,,,True
57eb12d93057a4bc1a043420327251b2327c9b39,biorxiv,"Real-time projections of Ebola outbreak size and duration with and without vaccine use in Equateur, Democratic Republic of Congo, as of May 27, 2018",doi.org/10.1101/331447,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundAs of May 27, 2018, 54 cases of Ebola virus disease (EVD) were reported in Equateur Province, Democratic Republic of Congo. We used reported case counts and time series from prior outbreaks to estimate the current outbreak size and duration with and without vaccine use.\n\nMethodsWe modeled Ebola virus transmission using a stochastic branching process model with a negative binomial distribution, using both estimates of reproduction number R declining from supercritical to subcritical derived from past Ebola outbreaks, as well as a particle filtering method to generate a probabilistic projection of the future course of the outbreak conditioned on its reported trajectory to date; modeled using 0%, 44%, and 62% estimates of vaccination coverage. Additionally, we used the time series for 18 prior Ebola outbreaks from 1976 to 2016 to parameterize a regression model predicting the outbreak size from the number of observed cases from April 4 to May 27.\n\nResultsWith the stochastic transmission model, we projected a median outbreak size of 78 EVD cases (95% credible interval: 52, 125.4), 86 cases (95% credible interval: 53, 174.3), and 91 cases (95% credible interval: 52, 843.5), using 62%, 44%, and 0% estimates of vaccination coverage. With the regression model, we estimated a median size of 85.0 cases (95% prediction interval: 53.5, 216.6).\n\nConclusionsThis outbreak has the potential to be the largest outbreak in DRC since 2007. Vaccines are projected to limit outbreak size and duration but are only part of prevention, control, and care strategies.",2018-06-04,"Kelly, J. D.; Worden, L.; Wannier, R.; Hoff, N. A.; Mukadi, P.; Sinai, C.; Ackley, S.; Chen, X.; Gao, D.; Selo, B.; Mossoko, M.; Okitolonda-Wemakoy, E.; Richardson, E. T.; Rutherford, G. W.; Lietman, T. M.; Muyembe-Tamfum, J. J.; Rimoin, A. W.; Porco, T. C.",,,,True
558d318e1655da9f5e9507ccf24fc773a0d377ff,biorxiv,Connectivity analyses of bioenergetic changes in schizophrenia: Identification of novel treatments,doi.org/10.1101/338392,,,See https://www.biorxiv.org/about-biorxiv,"We utilized a cell-level approach to examine glycolytic pathways in the DLPFC of subjects with schizophrenia (n=16) and control (n=16) subjects and found decreased mRNA expression of glycolytic enzymes in pyramidal neurons, but not astrocytes. To replicate these novel bioenergetic findings, we probed independent datasets for bioenergetic targets and found similar abnormalities. Next, we used a novel strategy to build a schizophrenia bioenergetic profile by a tailored application of the Library of Integrated Network-Based Cellular Signatures data portal (iLINCS) and investigated connected cellular pathways, kinases, and transcription factors using Enrichr. Finally, with the goal of identifying drugs capable of \""reversing\"" the bioenergetic schizophrenia signature, we performed a connectivity analysis with iLINCS and identified peroxisome proliferator-activated receptor (PPAR) agonists as promising therapeutic targets. We administered a PPAR agonist to the GluN1 knockdown model of schizophrenia and found it improved long-term memory. Taken together, our findings suggest that tailored bioinformatics approaches, coupled with the LINCS library of transcriptional signatures of chemical and genetic perturbagens may be employed to identify novel treatment strategies for schizophrenia and related diseases.",2018-06-05,"Sullivan, C. R.; Mielnik, C.; O'Donovan, S. M.; Funk, A.; Bentea, E.; Carey, E.; Wen, Z.; Haroutunian, V.; Katsel, P.; Ramsey, A. J.; Meller, J.; McCullumsmith, R.",,,,True
982a6fe2fdba30430b547741811ff4411f1485f1,biorxiv,Molecular basis for the evolution of species-specific hemoglobin capture by pathogenic Staphylococcus,doi.org/10.1101/339705,,,See https://www.biorxiv.org/about-biorxiv,"Metals are a limiting resource for pathogenic bacteria and must be scavenged from host proteins. Hemoglobin provides the most abundant source of iron in the human body and is required by several pathogens to cause invasive disease. However, the consequences of hemoglobin evolution for bacterial nutrient acquisition remain unclear. Here we show that the - and {beta}-globin genes exhibit strikingly parallel signatures of adaptive evolution across simian primates. Rapidly evolving sites in hemoglobin correspond to binding interfaces of IsdB, a bacterial hemoglobin receptor encoded by pathogenic Staphylococcus aureus. Using an evolution-guided experimental approach, we demonstrate that divergence between primates and staphylococcal isolates governs hemoglobin recognition and bacterial growth. Reintroducing putative adaptive mutations in - or {beta}-globin proteins is sufficient to impair S. aureus binding, providing a mechanism for the evolution of disease resistance. These findings suggest that bacterial hemoprotein capture has driven repeated evolutionary conflicts with hemoglobin during primate descent.",2018-06-07,"Choby, J. E.; Buechi, H. B.; Farrand, A. J.; Skaar, E. P.; Barber, M. F.",,,,True
0acc1f9a1c333a9a6b2dbba4a252d7576f024783,biorxiv,"SKEMPI 2.0: An updated benchmark of changes in protein-protein binding energy, kinetics and thermodynamics upon mutation",doi.org/10.1101/341735,,,See https://www.biorxiv.org/about-biorxiv,"MotivationUnderstanding the relationship between the sequence, structure, binding energy, binding kinetics and binding thermodynamics of protein-protein interactions is crucial to understanding cellular signaling, the assembly and regulation of molecular complexes, the mechanisms through which mutations lead to disease, and protein engineering.\n\nResultsWe present SKEMPI 2.0, a major update to our database of binding free energy changes upon mutation for structurally resolved protein-protein interactions. This version now contains manually curated binding data for 7085 mutations, an increase of 133%, including changes in kinetics for 1844 mutations, enthalpy and entropy changes for 443 mutations, and 440 mutations which abolish detectable binding.\n\nAvailabilityThe database is available at https://life.bsc.es/pid/skempi2/",2018-06-07,"Jankauskaite, J.; Jimenez-Garcia, B.; Dapkunas, J.; Fernandez-Recio, J.; Moal, I. H.",,,,True
58bc0f2712ea1ced1f886c9fdd17b8cf014e66cb,biorxiv,The Influence Of Social Behavior On Competition Between Virulent Pathogen Strains,doi.org/10.1101/293936,,,See https://www.biorxiv.org/about-biorxiv,"1Infectious disease interventions like contact precautions and vaccination have proven effective in disease control and elimination. The priority given to interventions can depend strongly on how virulent the pathogen is, and interventions may also depend partly for their success on social processes that respond adaptively to disease dynamics. However, mathematical models of competition between pathogen strains with differing natural history profiles typically assume that human behaviour is fixed. Here, our objective is to model the influence of social behaviour on the competition between pathogen strains with differing virulence. We couple a compartmental Susceptible-Infectious-Recovered model for a resident pathogen strain and a mutant strain with higher virulence, with a differential equation of a population where individuals learn to adopt protective behaviour from others according to the prevalence of infection of the two strains and the perceived severity of the respective strains in the population. We perform invasion analysis, time series analysis and phase plane analysis to show that perceived severities of pathogen strains and the efficacy of infection control against them can greatly impact the invasion of more virulent strain. We demonstrate that adaptive social behaviour enables invasion of the mutant strain under plausible epidemiological scenarios, even when the mutant strain has a lower basic reproductive number than the resident strain. Surprisingly, in some situations, increasing the perceived severity of the resident strain can facilitate invasion of the more virulent mutant strain. Our results demonstrate that for certain applications, it may be necessary to include adaptive social behaviour in models of the emergence of virulent pathogens, so that the models can better assist public health efforts to control infectious diseases.",2018-06-08,"Pharaon, J.; Bauch, C.",,,,True
4ed084719f40fac25989dbc99d08c2c609b33289,biorxiv,G-quadruplex forming sequences in the genome of all known human viruses: a comprehensive guide,doi.org/10.1101/344127,,,See https://www.biorxiv.org/about-biorxiv,"G-quadruplexes are non-canonical nucleic acid structures that control transcription, replication, and recombination in organisms. G-quadruplexes are present in eukaryotes, prokaryotes, and viruses. In the latter, mounting evidence indicates their key biological activity. Since data on viruses are scattered, we here present a comprehensive analysis of putative G-quadruplexes in the genome of all known viruses that can infect humans. We show that the presence, distribution, and location of G-quadruplexes are features characteristic of each virus class and family. Our statistical analysis proves that their presence within the viral genome is orderly arranged, as indicated by the possibility to correctly assign up to two-thirds of viruses to their exact class based on the G-quadruplex classification. For each virus we provide: i) the list of all G-quadruplexes formed by GG-, GGG- and GGGG-islands present in the genome (positive and negative strands), ii) their position in the viral genome along with the known function of that region, iii) the degree of conservation among strains of each G-quadruplex in its genome context, iv) the statistical significance of G-quadruplex formation. This information is accessible from a database (http://www.medcomp.medicina.unipd.it/main_site/doku.php?id=g4virus) to allow the easy and interactive navigation of the results. The availability of these data will greatly expedite research on G-quadruplex in viruses, with the possibility to accelerate finding therapeutic opportunities to numerous and some fearsome human diseases.",2018-06-11,"Lavezzo, E.; Berselli, M.; Frasson, I.; Perrone, R.; Palu, G.; Brazzale, A.; Richter, S.; Toppo, S.",,,,True
a7a4a5568e5b7c921bc616eedf532a393229decb,biorxiv,Gene birth contributes to structural disorder encoded by overlapping genes,doi.org/10.1101/229690,,,See https://www.biorxiv.org/about-biorxiv,"The same nucleotide sequence can encode two protein products in different reading frames. Overlapping gene regions encode higher levels of intrinsic structural disorder (ISD) than non-overlapping genes (39% vs. 25% in our viral dataset). This might be because of the intrinsic properties of the genetic code, because one member per pair was recently born de novo in a process that favors high ISD, or because high ISD relieves increased evolutionary constraint imposed by dual-coding. Here we quantify the relative contributions of these three alternative hypotheses. We estimate that the recency of de novo gene birth explains 32% or more of the elevation in ISD in overlapping regions of viral genes. While the two reading frames within a same-strand overlapping gene pair have markedly different ISD tendencies that must be controlled for, their effects cancel out to make no net contribution to ISD. The remaining elevation of ISD in the older members of overlapping gene pairs, presumed due to the need to alleviate evolutionary constraint, was already present prior to the origin of the overlap. Same-strand overlapping gene birth events can occur in two different frames, favoring high ISD either in the ancestral gene or in the novel gene; surprisingly, most de novo gene birth events contained completely within the body of an ancestral gene favor high ISD in the ancestral gene (23 phylogenetically independent events vs. 1). This can be explained by mutation bias favoring the frame with more start codons and fewer stop codons.",2018-06-13,"Willis, S.; Masel, J.",,,,True
736b4793b11d01f4b55ea53eaf59f7325493b27b,biorxiv,Knowledge and attitudes of Ebola among the general public of Trinidad and Tobago during the 2014-15 West Africa outbreak,doi.org/10.1101/346999,,,See https://www.biorxiv.org/about-biorxiv,"ObjectiveHealth system resilience and resilience of a country include the capacity of health personnel, institutions, and populations to prepare for and effectively respond to crises. This study investigates the knowledge and attitudes of the public concerning Ebola Virus Disease in Trinidad and Tobago.\n\nDesign and MethodsA cross sectional study whereby respondents (n = 920) were sampled from public places. Data were collected via interviewer administered questionnaires. Data were analysed using SPSS version 23.\n\nResultsThe response rate was 67.6 % (622/920). The main age category of responders was the 20 to 30 year age category (40.5%); responders were mostly female (58.0 %). Regarding knowledge, there were significant differences among occupational categories (F = 2.811, df1 = 6, df2 = 571, p-value = 0.011). Tukeys HSD post hoc test revealed that the mean knowledge scores for professional and sales occupations differed significantly (p-value = 0.003). There was a significant association between being afraid to go for treatment and age (p-value = 0.001). Significant associations were also found between occupational grouping and education attainment with opinion about the preparedness of private medical facilities, likelihood to shun family members with Ebola, being afraid to go for treatment and preference for traditional medicine (p-value <0.05).\n\nConclusionThis study highlights opportunities for community engagement to enhance health system resilience during outbreaks which would maximise national and global health security.",2018-06-14,"Pooransingh, S.; Mohammed, S.; Melville, K.; Mohammed, C.; Mohammed, M.; Mohammed, R. A.; Mootoo, W.; Motilal, D.; Morris, M.; Bhagwandeen, B.; Dialsingh, I.",,,,True
c5bf5beb177c16aa29255e89e0cf47e4e9467cce,biorxiv,The impact of news exposure on collective attention in the United States during the 2016 Zika epidemic,doi.org/10.1101/346411,,,See https://www.biorxiv.org/about-biorxiv,"In recent years, many studies have drawn attention to the important role of collective awareness and human behaviour during epidemic outbreaks. A number of modelling efforts have investigated the interaction between the disease transmission dynamics and human behaviour change mediated by news coverage and by information spreading in the population. Yet, given the scarcity of data on public awareness during an epidemic, few studies have relied on empirical data. Here, we use fine-grained, geo-referenced data from three online sources - Wikipedia, the GDELT Project and the Internet Archive - to quantify population-scale information seeking about the 2016 Zika virus epidemic in the U.S., explicitly linking such behavioural signal to epidemiological data. Geolocalized Wikipedia pageview data reveal that visiting patterns of Zika-related pages in Wikipedia were highly synchronized across the United States and largely explained by exposure to national television broadcast. Contrary to the assumption of some theoretical models, news volume and Wikipedia visiting patterns were not significantly correlated with the magnitude or the extent of the epidemic. Attention to Zika, in terms of Zika-related Wikipedia pageviews, was high at the beginning of the outbreak, when public health agencies raised an international alert and triggered media coverage, but subsequently exhibited an activity profile that suggests nonlinear dependencies and memory effects in the relation between information seeking, media pressure, and disease dynamics. This calls for a new and more general modelling framework to describe the interaction between media exposure, public awareness and disease dynamics during epidemic outbreaks.",2018-06-17,"Tizzoni, M.; Panisson, A.; Paolotti, D.; Cattuto, C.",,,,True
dc3d8b94ae9acb1ec585507d0d77164a7f688d10,biorxiv,Inflammation induced by influenza virus impairs innate control of human pneumococcal carriage,doi.org/10.1101/347161,,,See https://www.biorxiv.org/about-biorxiv,"Secondary bacterial pneumonia following influenza infection is a significant cause of mortality worldwide. Upper respiratory tract pneumococcal carriage is important as both determinants of disease and population transmission. The immunological mechanisms that contain pneumococcal carriage are well-studied in mice but remain unclear in humans. Loss of this control of carriage following influenza infection is associated with secondary bacterial pneumonia during seasonal and pandemic outbreaks. We used a human type 6B pneumococcal challenge model to show that carriage acquisition induces early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function associated with clearance of pneumococcal carriage. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate function and altered genome-wide nasal gene responses to pneumococcal carriage. Levels of the cytokine IP-10 promoted by viral infection at the time of pneumococcal encounter was positively associated with bacterial density. These findings provide novel insights in nasal immunity to pneumococcus and viral-bacterial interactions during co-infection.",2018-06-20,"Jochems, S. P.; Marcon, F.; Carniel, B. F.; Holloway, M.; Mitsi, E.; Smith, E.; Gritzfeld, J. F.; Solorzano, C.; Reine, J.; Pojar, S.; Nikolaou, E.; German, E. L.; Hyder-Wright, A.; Hill, H.; Hales, C.; de Steenhuijsen Piters, W. A. A.; Bogaert, D.; Adler, H.; Zaidi, S.; Connor, V.; Rylance, J.; Nakaya, H. I.; Ferreira, D. M.",,,,True
20154fa12ca525582cd1b42019927e8f7816fb51,biorxiv,Validation and automation of a high-throughput multi-targeted method for semi-quantification of endogenous metabolites from different biological matrices using tandem mass spectrometry,doi.org/10.1101/352468,,,See https://www.biorxiv.org/about-biorxiv,"The use of metabolomics profiling to understand metabolism under different physiological states has increased in recent years, which created the need for robust analytical platforms. Here, we present a validated method for targeted and semi-quantitative analysis of 102 polar metabolites that covers major metabolic pathways from 24 classes in a single 17.5-min assay. The method has been optimized for a wide range of biological matrices from various organisms, and involves automated sample preparation, and data processing using in-house developed R package. To ensure reliability, the method was validated for accuracy, precision, selectivity, specificity, linearity, recovery, and stability according to European Medicines Agency guidelines. We demonstrated excellent repeatability of the retention times (CV<4%), calibration curves (R2[&ge;]0.980) in their respective wide dynamic concentration ranges (CV<3%), and concentrations (CV<25%) of quality control samples interspersed within 25 batches analyzed over a period of one-year. The robustness was demonstrated through high correlation between metabolite concentrations measured using our method and NIST reference values (R2=0.967), including cross-platform comparability against the BIOCRATES AbsoluteIDQp180 kit (R2=0.975) and NMR analyses (R2=0.884). We have shown that our method can be successfully applied in many biomedical research fields and clinical trials, including epidemiological studies for biomarker discovery. In summary, a thorough validation demonstrated that our method is reproducible, robust, reliable, and suitable for metabolomics studies.",2018-06-20,"Nandania, J.; Peddinti, G.; Pessia, A.; Kokkonen, M.; Velagapudi, V.",,,,True
906b616191eea5e5e724d47546f7d2d9d096ed7a,biorxiv,Ensemble Feature Selection and Meta-Analysis of Cancer miRNA Biomarkers,doi.org/10.1101/353201,,,See https://www.biorxiv.org/about-biorxiv,"The role of microRNAs (miRNAs) in cellular processes captured the attention of many researchers, since their dysregulation is shown to affect the cancer disease landscape by sustaining proliferative signaling, evading program cell death, and inhibiting growth suppressors. Thus, miRNAs have been considered important diagnostic and prognostic biomarkers for several types of tumors. Machine learning algorithms have proven to be able to exploit the information contained in thousands of miRNAs to accurately predict and classify cancer types. Nevertheless, extracting the most relevant miRNA expressions is fundamental to allow human experts to validate and make sense of the results obtained by automatic algorithms. We propose a novel feature selection approach, able to identify the most important miRNAs for tumor classification, based on consensus on feature relevance from high-accuracy classifiers of different typologies. The proposed methodology is tested on a real-world dataset featuring 8,129 patients, 29 different types of tumors, and 1,046 miRNAs per patient, taken from The Cancer Genome Atlas (TCGA) database. A new miRNA signature is suggested, containing the 100 most important oncogenic miRNAs identified by the presented approach. Such a signature is proved to be sufficient to identify all 29 types of cancer considered in the study, with results nearly identical to those obtained using all 1,046 features in the original dataset. Subsequently, a meta-analysis of the medical literature is performed to find references to the most important biomarkers extracted by the methodology. Besides known oncomarkers, 15 new miRNAs previously not ranked as important biomarkers for diagnosis and prognosis in cancer pathologies are uncovered. Such miRNAs, considered relevant by the machine learning algorithms, but still relatively unexplored by specialized literature, could provide further insights in the biology of cancer.",2018-06-21,"Lopez-Rincon, A.; Martinez-Archundia, M.; Martinez-Ruiz, G. U.; Tonda, A.",,,,True
d1c77a93f69b5dbcf3806674bff9fe4677209ae5,biorxiv,Infectious bronchitis virus attaches to lipid rafts and enters cells via clathrin mediated endocytosis,doi.org/10.1101/352898,,,See https://www.biorxiv.org/about-biorxiv,"Due to its economic importance to in poultry industry, the biology and pathogenesis of infectious bronchitis virus (IBV) have been investigated extensively. However, the molecular mechanisms involved in IBV entry are not well characterized. In this study, systematic approaches were used to dissect IBV entry process in various susceptible cells. First, we observed that lipid rafts were involved in IBV attachment. Second, low pH in intracyplasmic vesicles was required for virus entry. By using the specific clathrin mediated endocytosis (CME) inhibitor or knock down of clathrin heavy chain (CHC), we demonstrated that IBV mainly utilized the CME for its entry. Furthermore, GTPase dynamin1 was involved in virus containing vesicle scission and internalization. Surprisingly, CME adaptor Eps15 had no effect on IBV internalization. Third, the penetration of IBV into cells led to active cytoskeleton rearrangement. After internalization, virus particles moved along with the classical endosome/lysosome track, as evidenced by co-localization of R18 labeled IBV with vehicle markers Rab5/Rab7/LAMP1 along with the infection time course. Functional inactivation of Rab5 and Rab7 significantly inhibited IBV infection. VCP, a protein helps early endosome maturation, was involved virus trafficking. Finally, by using the dual R18/DiOC labeled IBV, we observed that membrane fusion with late endosome/lysosome membranes was induced between 2-3 h.p.i.. Taken together, our findings demonstrate that IBV virions attach to lipid rafts and are internalized into cells via CME, move along with early/late endosomes-lysosomes, finally fuse with late endosome-lysosome membranes, release virus genome into cytoplasm. This study provides comprehensive images of IBV attachment-internalization-trafficking-fusion steps.\n\nIMPORTANCEIBV, the avian coronavirus isolated in 1937, infects chicken and causes economic loss in poultry industry. It has been reported that the entry of IBV requires low pH. However, the molecular mechanisms underlying IBV internalization and trafficking remain to be clarified. Therefore, we employed multiple chemical and molecular approaches to dissect the entry mechanisms of IBV in susceptible cells. Our results showed IBV entry was significantly inhibited when clathrin-mediated endocytosis (CME) was blocked by chemical inhibitor or depletion of clathrin protein. Moreover, by using R18-labeled IBV, we found that IBV particles attached to lipid rafts, led to actin rearrangement, and moved along with the entire endosomal system. R18/DiOC labeling method showed that IBV fused with late endosomes or lysosomes. This is the first report to describe the entire entry process of IBV, allowing for a better understanding of the infection process of group III avian coronavirus.",2018-06-21,"Wang, H.; Sun, Y.; Mao, X.; Meng, C.; Tan, L.; Song, C.; Qiu, X.; Ding, C.; Liao, Y.",,,,True
ae4f1ac93bb55da1231f08eb1654f19352ab1a3f,biorxiv,"Viral etiology of Acute Respiratory Infections in Hospitalized Children in Novosibirsk City, Russia (2013 - 2017)",doi.org/10.1101/353037,,,See https://www.biorxiv.org/about-biorxiv,"Introduction Introduction Materials and methods Results Discussion References Acute respiratory infections (ARIs) pose a significant public health problem worldwide, causing considerable morbidity and mortality among people of all age groups [1]. Children are on average infected two to three times more frequently than adults. [2]. There are more than 200 respiratory viruses that can cause ARIs. Respiratory syncytial virus (RSV), human rhinovirus (HRV), human metapneumovirus (HMPV), human parainfluenza virus (PIV), human enterovirus (EV), influenza virus (IFV), human coronavirus (CoV), adenovirus (ADV), and human bocavirus (BoV) are the most common viral agents associated with ARIs, accounting for around 70 % of ARIs [3, 4]. The frequency of mixed respiratory viral ...",2018-06-21,"Kurskaya, O.; Ryabichenko, T.; Leonova, N.; Shi, W.; Bi, H.; Sharshov, K.; Kazachkova, E.; Sobolev, I.; Prokopyeva, E.; Kartseva, T.; Alekseev, A.; Shestopalov, A.",,,,True
83cca3779f8aeea47c5426e1d0fa65f1e9567e0c,biorxiv,G-quadruplex stabilization in the ions and maltose transporters inhibit Salmonella enterica growth and virulence.,doi.org/10.1101/357046,,,See https://www.biorxiv.org/about-biorxiv,"The G-quadruplex structure forming motifs have recently emerged as a novel therapeutic drug target in various human pathogens. Herein, we report three highly conserved G-quadruplex motifs (SE-PGQ-1, 2, and3) in genome of all the 412 strains of Salmonella enterica. Bioinformatics analysis inferred the presence of SE-PGQ-1 in the regulatory region of mgtA, presence of SE-PGQ-2 in the open reading frame of entA and presence of SE-PGQ-3 in the promoter region of malE and malK genes. The products of mgtA and entA are involved in transport and homeostasis of Mg2+ and Fe3+ ion and thereby required for bacterial survival in the presence of reactive nitrogen/oxygen species produced by the host macrophages, whereas, malK and malE genes are involved in transport of maltose sugar, that is one of the major carbon source in the gastrointestinal tract of human. The formation of stable intramolecular G-quadruplex structures by SE-PGQs was confirmed by employing CD, EMSA and NMR spectroscopy. Cellular studies revealed the inhibitory effect of 9-amino acridine on Salmonella enterica growth. Next, CD melting analysis demonstrated the stabilizing effect of 9-amino acridine on SE-PGQs. Further, polymerase inhibition and RT-qPCR assays emphasize the biological relevance of predicted G-quadruplex in the expression of PGQ possessing genes and demonstrate the G-quadruplexes as a potential drug target for the devolping novel therapeutics for combating Salmonella enterica infection.\n\nAuthor SummarySince last several decades scientific community has witnessed a rapid increase in number of such human pathogenic bacterial species that acquired resistant to multiple antibacterial agents. Currently, emergence of multidrug-resistant strains remain a major public health concern for clinical investigators that rings a global alarm to search for novel and highly conserved drug targets. Recently, G-quadruplex structure forming nucleic acid sequences were endorsed as highly conserved Drug target for preventing infection of several human pathogens including viral and protozoan species. Therefore, here we explored the presence G-quadruplex forming motif in genome of Salmonella enterica bacteria that causes food poisoning, and enteric fever in human. The formation of intra molecular G-quadruplex structure in four genes (mgtA, entA, malE and malK) was confirmed by NMR, CD and EMSA. The 9-amino acridine, a known G-quadruplex binder has been shown to stabilize the predicted G-quadruplex motif and decreases the expressioin of G-quadruplex hourbouring genes using RT-PCR and cellular toxicity assay. This study concludes the presence of G-quadruplex motifs in essential genes of Salmonella enterica genome as a novel and conserved drug target and 9-amino acridine as candidate small molecule for preventing the infection of Salmonella enterica using a G4 mediated inhibition mechanism.",2018-06-27,"jain, N.; Mishra, S. K.; Shankar, U.; Tawani, A.; Jaiswal, A.; Sharma, T. K.; Kodgire, P.; Kumar, A.",,,,True
b9b0cad2db02479624a3d087626811e4d2fbcdb9,biorxiv,Changes in temperature alter susceptibility to a virus following a host shift,doi.org/10.1101/358564,,,See https://www.biorxiv.org/about-biorxiv,"Host shifts - where a pathogen jumps between different host species - are an important source of emerging infectious disease. With ongoing climate change there is an increasing need to understand the effect changes in temperature may have on emerging infectious disease. We investigated whether species susceptibilities change with temperature and ask if susceptibility is greatest at different temperatures in different species. We infected 45 species of Drosophilidae with an RNA virus and measured how viral load changes with temperature. We found the host phylogeny explained a large proportion of the variation in viral load at each temperature, with strong phylogenetic correlations between viral loads across temperature. The variance in viral load increased with temperature, whilst the mean viral load did not, such that as temperature increased the most susceptible species become more susceptible, and the least susceptible less so. We found no significant relationship between a species susceptibility across temperatures and proxies for thermal optima; critical thermal maximum and minimum or basal metabolic rate. These results suggest that whilst the rank order of species susceptibilities can remain the same with changes in temperature, the likelihood of host shifts into a given species may increase or decrease.\n\nAuthor SummaryEmerging infectious diseases are often the result of a host shift, where a pathogen jumps from one host species into another. Understanding the factors underlying host shifts is a major goal for infectious disease researchers. This effort has been further complicated by the fact that host-parasite interactions are now taking place in a period of unprecedented global climatic warming. Here, we ask how host shifts are affected by temperature by carrying out experimental infections using an RNA virus across a wide range of related species, at three different temperatures. We find that as temperature increases the most susceptible species become more susceptible, and the least susceptible less so. This has important consequences for our understanding of host shift events in a changing climate, and suggests that temperature changes may affect the likelihood of a host shift into certain species.",2018-06-28,"Roberts, K.; Hadfield, J. D.; Sharma, M. D.; Longdon, B.",,,,True
7b89a657dde3e5888c31d1d5ef3b90ceb0f66a62,biorxiv,Beyond type 1 regulatory T cells: co-expression of LAG3 and CD49b in IL-10-producing T cell lineages,doi.org/10.1101/359547,,,See https://www.biorxiv.org/about-biorxiv,"Type 1 regulatory CD4+ T (Tr1) cells express high levels of the immunosuppressive cytokine IL-10 but not the master transcription factor Foxp3, and can suppress inflammation and promote immune tolerance. In order to identify and obtain viable Tr1 cells for research and clinical applications, co-expression of CD49b and LAG3 has been proposed as a unique surface signature for both human and mouse Tr1 cells. However, recent studies have revealed that this pattern of co-expression is dependent on the stimulating conditions and the differentiation stage of the CD4+ T cells. Here, using an IL-10GFP/Foxp3RFP dual reporter transgenic murine model, we demonstrate that co-expression of CD49b and LAG3 is not restricted to the Foxp3- Tr1 cells, but is also observed in Foxp3+ T regulatory (Treg) cells and CD8+ T cells that produce IL-10. Our data indicate that IL-10-producing Tr1 cells, Treg cells and CD8+ T cells are all capable of co-expressing LAG3 and CD49b in vitro following differentiation under IL-10-inducing conditions, and in vivo following pathogenic insult or infection in the pulmonary mucosa. Our findings urge caution in the use of LAG3/CD49b co-expression to identify Tr1 cells, since it may mark IL-10-producing T cell lineages more broadly, including the Foxp3- Tr1 cells, Foxp3+ Treg cells and CD8+ T cells.",2018-06-30,"Huang, W.; Solouki, S.; Carter, C.; Zheng, S.-G.; August, A.",,,,True
a3dcd6b3f0551e607d0235616109ab8d506f81a2,biorxiv,Analyzing Vaccine Trials in Epidemics with Mild and Asymptomatic Infection,doi.org/10.1101/295337,,,See https://www.biorxiv.org/about-biorxiv,"Vaccine efficacy against susceptibility to infection (VES), regardless of symptoms, is an important endpoint of vaccine trials for pathogens with a high proportion of asymptomatic infection, as such infections may contribute to onward transmission and outcomes such as Congenital Zika Syndrome. However, estimating VES is resource-intensive. We aim to identify methods to accurately estimate VEs when limited information is available and resources are constrained. We model an individually randomized vaccine trial by generating a network of individuals and simulating an epidemic. The disease natural history follows a Susceptible, Exposed, Infectious and Symptomatic or Infectious and Asymptomatic, Recovered model. We then use seven approaches to estimate VES, and we also estimate vaccine efficacy against progression to symptoms (VEP). A corrected relative risk and an interval censored Cox model accurately estimate VES and only require serologic testing of participants once, while a Cox model using only symptomatic infections returns biased estimates. Only acquiring serological endpoints in a 10% sample and imputing the remaining infection statuses yields unbiased VES estimates across values of R0 and accurate estimates of VEP for higher values. Identifying resource-preserving methods for accurately estimating VES is important in designing trials for diseases with a high proportion of asymptomatic infection.",2018-07-02,"Kahn, R.; Hitchings, M.; Wang, R.; Bellan, S.; Lipsitch, M.",,,,True
df6013a1630aa41627cc84c8e780d40ff93785cc,biorxiv,A method for RNA structure prediction shows evidence for structure in lncRNAs,doi.org/10.1101/284869,,,See https://www.biorxiv.org/about-biorxiv,"To compare the secondary structures of RNA molecules we developed the CROSSalign method. CROSSalign is based on the combination of the Computational Recognition Of Secondary Structure (CROSS) algorithm to predict the RNA secondary structure at single-nucleotide resolution using sequence information, and the Dynamic Time Warping (DTW) method to align profiles of different lengths. We applied CROSSalign to investigate the structural conservation of long non-coding RNAs such as XIST and HOTAIR as well as ssRNA viruses including HIV. In a pool of sequences with the same secondary structure CROSSalign accurately recognizes repeat A of XIST and domain D2 of HOTAIR and outperforms other methods based on covariance modelling. CROSSalign can be applied to perform pair-wise comparisons and is able to find homologues between thousands of matches identifying the exact regions of similarity between profiles of different lengths. The algorithm is freely available at the webpage http://service.tartaglialab.com//new_submission/CROSSalign.",2018-07-03,"Delli Ponti, R.; Armaos, A.; Marti, S.; Tartaglia, G. G.",,,,True
10424da2599f0258bfaf71a3186b999ab2d747d0,biorxiv,"Risk of disease spillover from dogs to wild carnivores in Kanha Tiger Reserve, India.",doi.org/10.1101/360271,,,See https://www.biorxiv.org/about-biorxiv,"Many mammalian carnivore species have been reduced to small, isolated populations by habitat destruction, fragmentation, poaching, and human conflict. Their limited genetic variability and increased exposure to domestic animals such as dogs place them at risk of further losses from infectious diseases. In India, domestic and feral dogs are associated with villages in and around protected areas, and may serve as reservoirs of pathogens to the carnivores within. Indias Kanha Tiger Reserve (KTR) is home to a number of threatened and endangered mammalian carnivores including tiger (Panthera tigris), leopard (Panthera pardus), wolf (Canis lupus), and dhole (Cuon alpinus). It also has more than 150 villages with associated dog populations. We found that dog populations ranged from 14 to 45/village (3.7 to 23.7/km2), and did not vary with village area, human population size, or distance from the KTRs core area, though they all increased between summer 2014 and winter 2015, primarily through reproduction. No dog tested positive for rabies but seroprevalence levels to three other generalist viral pathogens were high in summer (N=67) and decreased somewhat by winter (N=168): canine parvovirus (83.6% to 68.4%), canine distemper virus (50.7% to 30.4%) and canine adenovirus (41.8% to 30.9%). The declines in seroprevalence were primarily due to new recruitments by birth and these were not yet exposed to the viruses. Wild carnivores frequently entered the villages, as shown by tracks, scats, kills and other indicators, and the dogs are known to leave the villages so that encounters between dogs and wild carnivores may be common. We conclude that there is a large population of unvaccinated dogs in and around Kanha Tiger Reserve, with high levels of seroprevalence to pathogens with broad host ranges and these dogs which interact with wild carnivores, therefore posing a high risk of disease spillover to the wild carnivores.",2018-07-03,"chaudhary, v.; Rajput, N.; Shrivastav, A. B.; Tonkyn, D.",,,,True
6cbefcf4c0fbb8466db7d00b8f53e1f37a6bf8b5,biorxiv,Integrated Disease Surveillance and Response (IDSR) in Malawi: Implementation Gaps and Challenges for Timely Alert,doi.org/10.1101/363713,,,See https://www.biorxiv.org/about-biorxiv,"ObjectiveThe emerging and recent 2014 Ebola Virus Disease (EVD) outbreaks rang the bell to call upon efforts from globe to assist resource-constrained countries to strengthen public health surveillance system for early response. Malawi adopted the Integrated Disease Surveillance and Response (IDSR) strategy to develop its national surveillance system since 2002 and revised its guideline to fulfill the International Health Regulation (IHR) requirements in 2014. This study aimed to understand the state of IDSR implementation and differences between guideline and practice for future disease surveillance system strengthening.\n\nMethodsThis was a mixed-method observational study. Quantitative data were to analyze completeness and timeliness of surveillance system performance from national District Health Information System 2 (DHIS2). Qualitative data were collected through interviews with 29 frontline health service providers from the selected district and key informants of the IDSR system implementation and administration at district and national levels.\n\nFindingsThe current IDSR system showed relatively good completeness (76.4%) but poor timeliness (41.5%) of total expected monthly reports nationwide and zero weekly reports. The challenges of IDSR implementation revealed through qualitative data included lack of supervision, inadequate resources for training and difficulty to implement weekly report due to overwhelming paperwork at frontline health services.\n\nConclusionsThe differences between IDSR technical guideline and actual practice were huge. The developing information technology infrastructure in Malawi and emerging mobile health (mHealth) technology can be opportunities for the country to overcome these challenges and improve surveillance system to have better timeliness for the outbreaks and unusual events detection.",2018-07-06,"Wu, T.-S. J.; Kagoli, M.; Kaasboll, J. J.; Bjune, G. A.",,,,True
180c88b68816bbb6eb57aa515a3aec4020178729,biorxiv,Inferring the presence of aflatoxin-producing Aspergillus flavus strains using RNA sequencing and electronic probes as a transcriptomic screening tool,doi.org/10.1101/365254,,,See https://www.biorxiv.org/about-biorxiv,"E-probe Diagnostic for Nucleic acid Analysis (EDNA) is a bioinformatic tool originally developed to detect plant pathogens in metagenomic databases. However, enhancements made to EDNA increased its capacity to conduct hypothesis directed detection of specific gene targets present in transcriptomic databases. To target specific pathogenicity factors used by the pathogen to infect its host or other targets of interest, e-probes need to be developed for transcripts related to that function. In this study, EDNA transcriptomics (EDNAtran) was developed to detect the expression of genes related to aflatoxin production at the transcriptomic level. E-probes were designed from genes up-regulated during A. flavus aflatoxin production. EDNAtran detected gene transcripts related to aflatoxin production in a transcriptomic database from corn, where aflatoxin was produced. The results were significantly different from e-probes being used in the transcriptomic database where aflatoxin was not produced (atoxigenic AF36 strain and toxigenic AF70 in Potato Dextrose Broth).",2018-07-09,"Espindola, A.; Schneider, W. D.; Cardwell, K. F.; Carrillo, Y. D.; Hoyt, P. D.; Marek, S. M.; Melouk, H. D.; Garzon, C. D.",,,,True
22264c65eb6c14ba96287ba4da536424dd083253,biorxiv,Quality control implementation for universal characterization of DNA and RNA viruses in clinical respiratory samples using single metagenomic next-generation sequencing workflow,doi.org/10.1101/367367,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundIn recent years, metagenomic Next-Generation Sequencing (mNGS) has increasingly been used for an accurate assumption-free virological diagnosis. However, the systematic workflow evaluation on clinical respiratory samples and implementation of quality controls (QCs) is still lacking.\n\nMethodsA total of 3 QCs were implemented and processed through the whole mNGS workflow: a notemplate-control to evaluate contamination issues during the process; an internal and an external QC to check the integrity of the reagents, equipment, the presence of inhibitors, and to allow the validation of results for each sample. The workflow was then evaluated on 37 clinical respiratory samples from patients with acute respiratory infections previously tested for a broad panel of viruses using semi-quantitative real-time PCR assays (28 positive samples including 6 multiple viral infections; 9 negative samples). Selected specimens included nasopharyngeal swabs (n = 20), aspirates (n = 10), or sputums (n = 7).\n\nResultsThe optimal spiking level of the internal QC was first determined in order to be sufficiently detected without overconsumption of sequencing reads. According to QC validation criteria, mNGS results were validated for 34/37 selected samples. For valid samples, viral genotypes were accurately determined for 36/36 viruses detected with PCR (viral genome coverage ranged from 0.6% to 100%, median = 67.7%). This mNGS workflow allowed the detection of DNA and RNA viruses up to a semi-quantitative PCR Ct value of 36. The six multiple viral infections involving 2 to 4 viruses were also fully characterized. A strong correlation between results of mNGS and real-time PCR was obtained for each type of viral genome (R2 ranged from 0.72 for linear single-stranded (ss) RNA viruses to 0.98 for linear ssDNA viruses).\n\nConclusionsAlthough the potential of mNGS technology is very promising, further evaluation studies are urgently needed for its routine clinical use within a reasonable timeframe. The approach described herein is crucial to bring standardization and to ensure the quality of the generated sequences in clinical setting. We provide an easy-to-use single protocol successfully evaluated for the characterization of a broad and representative panel of DNA and RNA respiratory viruses in various types of clinical samples.",2018-07-11,"Bal, A.; Pichon, M.; Picard, C.; Casalegno, J.-S.; Valette, M.; Scuffenecker, I.; Billard, L.; Vallet, S.; Vilchez, G.; Cheynet, V.; Oriol, G.; Trouillet-assant, S.; Gillet, Y.; Lina, B.; Brengel-pesce, K.; Morfin-sherpa, F.; Josset, L.",,,,True
41d412415c46baf70ca91ebf049c0352ead19f18,biorxiv,BAR scaffolds drive membrane fission by crowding disordered domains,doi.org/10.1101/276147,,,See https://www.biorxiv.org/about-biorxiv,"Cylindrical protein scaffolds are thought to stabilize membrane tubules, preventing membrane fission. In contrast, Snead et al. find that when scaffold proteins assemble, bulky disordered domains within them become acutely concentrated, generating steric pressure that destabilizes tubules, driving fission.\n\nAbstractCellular membranes are continuously remodeled. The crescent-shaped bin-amphiphysinrvs (BAR) domains remodel membranes in multiple cellular pathways. Based on studies of BAR domains in isolation, the current paradigm is that they polymerize into cylindrical scaffolds that stabilize lipid tubules, preventing membrane fission. But in nature BAR domains are often part of multi-domain proteins that contain large intrinsically-disordered regions. Using in vitro and live cell assays, here we show that full-length BAR domain-containing proteins, rather than stabilizing membrane tubules, are instead surprisingly potent drivers of membrane fission. Specifically, when BAR scaffolds assemble at membrane surfaces, their bulky disordered domains become crowded, generating steric pressure that destabilizes lipid tubules. More broadly, we observe this behavior with BAR domains that have a range of curvatures. These data challenge the idea that cellular membranes adopt the curvature of BAR scaffolds, suggesting instead that the ability to concentrate disordered domains is the key requirement for membrane remodeling and fission by BAR domain-containing proteins.",2018-07-16,"Snead, W. T.; Zeno, W. F.; Kago, G.; Perkins, R. W.; Richter, J. B.; Zhao, C.; Lafer, E. M.; Stachowiak, J. C.",,,,True
896cb03362facd2a670bee13dc5368b81768b2ba,biorxiv,"Zika Virus Infection At Different Pregnancy Stages: Anatomopathological Findings, Target Cells And Viral Persistence In Placental Tissues",doi.org/10.1101/370528,,,See https://www.biorxiv.org/about-biorxiv,"Zika virus (ZIKV) infection in humans has been associated with congenital malformations and other neurological disorders, such as Guillain-Barre syndrome. The mechanism(s) of ZIKV intrauterine transmission, the cell types involved, the most vulnerable period of pregnancy for severe outcomes from infection and other physiopathological aspects remain unknown. In this study, we analyzed placental samples obtained at the time of delivery from a group of twenty-four women diagnosed with ZIKV infection during the first, second or third trimesters of pregnancy. Villous immaturity was the main histological finding in the placental tissues, although placentas without alterations were also frequently observed. Significant enhancement of the number of syncytial sprouts was observed in the placentas of women infected during the third trimester, indicating the development of placental abnormalities after ZIKV infection. Hyperplasia of Hofbauer cells (HCs) was also observed in these third-trimester placental tissues, and remarkably, HCs were the only ZIKV-positive fetal cells found in the placentas studied that persisted until birth, as revealed by immunohistochemical (IHC) analysis. Thirty-three percent of women infected during pregnancy delivered infants with congenital abnormalities, although no pattern correlating the gestational stage at infection, the IHC positivity of HCs in placental tissues and the presence of congenital malformations at birth was observed. Placental tissue analysis enabled us to confirm maternal ZIKV infection in cases where serum from the acute infection phase was not available, which reinforces the importance of this technique in identifying possible causal factors of birth defects. The results we observed in the samples from naturally infected pregnant women may contribute to the understanding of some aspects of the pathophysiology of ZIKV.",2018-07-16,"Noronha, L.; Zanluca, C.; Burger, M.; Suzukawa, A. A.; Azevedo, M.; Rebutini, P.; Novadzki, I. M.; Tanabe, L. S.; Presibella, M. M.; Duarte dos Santos, C. N.",,,,True
e01948b342544a5fcd8c14d757501779029c6d6d,biorxiv,Chronic infections can shape epidemic exposure: Pathogen co-occurrence networks in the Serengeti lions,doi.org/10.1101/370841,,,See https://www.biorxiv.org/about-biorxiv,"Pathogens are embedded in a complex network of microparasites that can collectively or individually alter disease dynamics and outcomes. Chronic pathogens, for example, can either facilitate or compete with subsequent pathogens thereby exacerbating morbidity and mortality. Pathogen interactions are ubiquitous in nature, but poorly understood, particularly in wild populations. We report here on ten years of serological and molecular data in African lions, leveraging comprehensive demographic and behavioral data to utilize pathogen networks to test if chronic infections shape infection by acute pathogens. We combine network and community ecology approaches to assess broad network structure and characterize associations between pathogens across spatial and temporal scales. We found significant non-random structure in the lion-pathogen co-occurrence network and identified potential facilitative and competitive interactions between acute and chronic pathogens. Our results provide a novel insight for untangling the complex associations underlying pathogen co-occurrence networks.",2018-07-17,"Fountain-Jones, N. M.; Packer, C.; Jacquot, M.; Blanchet, G.; Terio, K.; Craft, M.",,,,True
500c5ea0961b573ba5355d364ca94c00a0a26e4a,biorxiv,The dengue virus non-structural protein 1 (NS1) is secreted from mosquito cells in association with the intracellular cholesterol transporter chaperone caveolin complex,doi.org/10.1101/370932,,,See https://www.biorxiv.org/about-biorxiv,"Dengue virus (DENV) is a mosquito-borne virus of the family Flaviviridae. The RNA viral genome encodes for a polyprotein that is co-translationally processed into three structural proteins and seven non-structural proteins. The non-structural protein 1 (NS1) is a multifunctional viral protein actively secreted in vertebrate and mosquito cells during DENV infection. In mosquito cells, NS1 is secreted in a caveolin-1 (CAV-1) dependent manner by an unconventional pathway. The caveolin chaperone complex (CCC) is a cytoplasmic complex formed by caveolin-1 and the chaperones FKBP52, Cy40 and CyA which is responsible for cholesterol traffic inside the cell. In this work, we demonstrate that in infected mosquito cells, DENV NS1 is secreted by an early and unconventional route that bypasses the Golgi apparatus in close association with the CCC. Treatment of mosquito cells with classic secretion inhibitors such as brefeldin A, golgicide A and Fli-06 showed no effect on NS1 secretion, but significant reductions in recombinant luciferase secretion and virion release. Silencing the expression of CAV1, FKBP52 with siRNAs or the inhibition of CyA by cyclosporine A resulted in significant decrease in NS1 secretion without affecting virion release. Using co-localization, co-inmunoprecipitation and proximity ligation assays, NS1 was found to co-localize and interact with all the protein components of the CCC in mosquito infected cells. In addition, CAV-1 and FKBP52 expression was found augmented in DENV infected cells. Finally, the treatment of ZIKV infected mosquito cells with brefeldin A and golgicide A showed no effect on NS1 secretion, while affecting virion release. ZIKV NS1 was also found to co-localize with CAV-1 in infected mosquito cells. These results suggest that in mosquito cells, ZIKV NS1 follows the same secretory pathway observed for DENV NS1. The association of NS1 with the cholesterol transporter CCC agrees with the lipoprotein nature of secreted hexameric NS1.\n\nAUTHOR SUMMARYDengue protein NS1 is secreted in infected mosquito and vertebrate cells. In humans, secreted NS1 have been associated with pathogenesis. In mosquito cells, NS1 follows an unconventional secretion pathway that is dependent on Caveolin-1. This work shows that in mosquito cells, NS1 secretion is associated to the chaperone caveolin complex, a complex formed by caveolin-1 and several chaperones, in charge of cholesterol transport within the cells. Reduction of the expression or the activity of chaperone caveolin complex in mosquito infected cells, diminished the secretion of NS1 without affecting virion release. Direct interaction between NS1 and the chaperone caveolin complex proteins was demonstrated by several assays. Moreover, increased expression of the caveolin-1 and co-chaperone FKBP52 during dengue infection was found, presumably in response to the higher requirements of these proteins during dengue virus infection. Results obtained with ZIKV infected mosquito cells suggest that also ZIKV NS1 is released following an unconventional secretory route in association with the chaperone caveolin complex. The functions of secreted NS1 within mosquito are unclear. However, giving the importance of the soluble NS1 in the vertebrate host, manipulation of the NS1 secretory route may prove a valuable strategy for dengue mosquito control and patient treatment.",2018-07-17,"Rosales Ramirez, R.; Ludert, J. E.",,,,True
e7c3ec3dcb3469ee4d608029e7aa3068a4c90c54,biorxiv,"The Role of Proton Transport in Gating Current in a Voltage Gated Ion Channel, as Shown by Quantum Calculations",doi.org/10.1101/371914,,,See https://www.biorxiv.org/about-biorxiv,"Over two-thirds of a century ago, Hodgkin and Huxley proposed the existence of voltage gated ion channels (VGIC) to carry Na+ and K+ ions across the cell membrane to create the nerve impulse, in response to depolarization of the membrane. The channels have multiple physiological roles, and play a central role in a wide variety of diseases when they malfunction. The first channel structure was found by MacKinnon and coworkers in 1998. Subsequently the structure of a number of VGIC was determined in the open (ion conducting) state. This type of channel consists of four voltage sensing domains (VSD), each formed from four transmembrane (TM) segments, plus a pore domain through which ions move. Understanding the gating mechanism (how the channel opens and closes) requires structures. One TM segment (S4) has an arginine in every third position, with one such segment per domain. It is usually assumed that these arginines are all ionized, and in the resting state are held toward the intracellular side of the membrane by voltage across the membrane. They are assumed to move outward (extracellular direction) when released by depolarization of this voltage, producing a capacitive gating current and opening the channel. We suggest alternate interpretations of the evidence that led to these models. Measured gating current is the total charge displacement of all atoms in the VSD; we propose that the prime, but not sole, contributor is proton motion, not displacement of the charges on the arginines of S4. It is known that the VSD can conduct protons. Quantum calculations on the Kv1.2 potassium channel VSD show how; the key is the amphoteric nature of the arginine side chain, which allows it to transfer a proton; this appears to be the first time the arginine side chain has had its amphoteric character considered. We have calculated one such proton transfer in detail: this proton starts from a tyrosine that can ionize, transferring to the NE of the third arginine on S4; that arginines NH then transfers a proton to a glutamate. The backbone remains static. A mutation predicted to affect the proton transfer has been qualitatively confirmed experimentally, from the change in the gating current-voltage curve. The total charge displacement in going from a normal closed potential of -70 mV across the membrane to 0 mV (open), is calculated to be approximately consistent with measured values, although the error limits on the calculation require caution in interpretation.",2018-07-19,"Kariev, A. M.; Green, M. E.",,,,True
69f473aee22a4ac8df15a54a6109b70b1ae9b7e7,biorxiv,HOPS-dependent endosomal fusion required for efficient cytosolic delivery of therapeutic peptides and small proteins,doi.org/10.1101/374926,,,See https://www.biorxiv.org/about-biorxiv,"Protein therapeutics represent a significant and growing component of the modern pharmacopeia, but their potential to treat human disease is limited because most proteins fail to traffic across biological membranes. Recently, we discovered that cell-permeant miniature proteins (CPMPs) containing a precisely defined, penta-arginine motif traffic readily to the cytosol and nucleus with efficiencies that rival those of hydrocarbon-stapled peptides active in animals and man. Like many cell-penetrating peptides (CPPs), CPMPs enter the endocytic pathway; the difference is that CPMPs are released efficiently from endosomes while other CPPs are not. Here, we seek to understand how CPMPs traffic from endosomes into the cytosol and what factors contribute to the efficiency of endosomal release. First, using two complementary cell-based assays, we exclude endosomal rupture as the primary means of endosomal escape. Next, using a broad spectrum of techniques, including an RNA interference (RNAi) screen, fluorescence correlation spectroscopy (FCS), and confocal imaging, we identify VPS39--a gene encoding a subunit of the homotypic fusion and protein sorting (HOPS) complex--as a critical determinant in the trafficking of CPMPs and hydrocarbon-stapled peptides to the cytosol. Although CPMPs neither inhibit nor activate HOPS function, HOPS activity is essential to efficiently deliver CPMPs to the cytosol. Subsequent multi-color confocal imaging studies identify CPMPs within the endosomal lumen, particularly within the intraluminal vesicles (ILVs) of Rab7+ and Lamp1+ endosomes that are the products of HOPS-mediated fusion. These results suggest that CPMPs require HOPS to reach ILVs--an environment that serves as a prerequisite for efficient endosomal escape.",2018-07-23,"Steinauer, A.; LaRochelle, J.; Wissner, R.; Berry, S.; Schepartz, A.",,,,True
110b4b089bd757bd54587c2ab3262a374462c098,biorxiv,The permeabilized SecY protein-translocation channel can serve as a nonspecific sugar transporter,doi.org/10.1101/378786,,,See https://www.biorxiv.org/about-biorxiv,"As the initial step in carbohydrate catabolism in cells, the substrate-specific transporters via active transport and facilitated diffusion play a decisive role in passage of sugars through the plasma membrane into the cytoplasm. The SecY complex (SecYEG) in bacteria forms a membrane channel responsible for protein translocation. This work demonstrates that weakening the sealability of the SecY channel allowed free diffusion of sugars, including glucose, fructose, mannose, xylose, arabinose, and lactose, into the engineered cells, facilitating its rapid growth on a wide spectrum of monosaccharides and bypassing/reducing stereospecificity, transport saturation, competitive inhibition, and carbon catabolite repression (CCR), which are usually encountered with the specific sugar transporters. The SecY channel is structurally conserved in prokaryotes, thus it may be engineered to serve as a unique and universal transporter for bacteria to passage sugars as demonstrated in Escherichia coli and Clostridium acetobutylicum.",2018-07-27,"Mei, S.; Xie, C.; Mi, H.; Xue, C.; Guo, Q.; Du, G.-Q.; Li, G.-B.; Li, C.-X.; Qu, Y.-N.; Xiong, M.-H.; Jiang, Y.; Tan, T.-W.; Yang, S.-T.; Fan, L.-H.",,,,True
6f8a531b4b84d4daaadcff9d7e03ee24274baf0b,biorxiv,"Etiology of fever in Ugandan children: identification of microbial pathogens using metagenomic next-generation sequencing and IDseq, a platform for unbiased metagenomic analysis",doi.org/10.1101/385005,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundFebrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. We built and employed IDseq, a cloud-based, open access, bioinformatics platform and service to identify microbes from metagenomic next-generation sequencing of tissue samples. In this pilot study, we evaluated blood, nasopharyngeal, and stool specimens from 94 children (aged 2-54 months) with febrile illness admitted to Tororo District Hospital, Uganda.\n\nResultsThe most common pathogens identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from blood; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. Among other potential pathogens, we identified one novel orthobunyavirus, tentatively named Nyangole virus, from the blood of a child diagnosed with malaria and pneumonia, and Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis. We also identified two novel human rhinovirus C species.\n\nConclusionsThis exploratory pilot study demonstrates the utility of mNGS and the IDseq platform for defining the molecular landscape of febrile infectious diseases in resource limited areas. These methods, supported by a robust data analysis and sharing platform, offer a new tool for the surveillance, diagnosis, and ultimately treatment and prevention of infectious diseases.",2018-08-06,"Ramesh, A.; Nakielny, S.; Hsu, J.; Kyohere, M.; Byaruhanga, O.; de Bourcy, C.; Egger, R.; Dimitrov, B.; Juan, Y.-F.; Sheu, J.; Wang, J.; Kalantar, K.; Langelier, C.; Ruel, T.; Mpimbaza, A.; Wilson, M. R.; Rosenthal, P. J.; DeRisi, J. L.",,,,True
0d7964c665ff0107c674bc6dab8f252cab08038e,biorxiv,A transmissible RNA pathway in honey bees,doi.org/10.1101/299800,,,See https://www.biorxiv.org/about-biorxiv,"One of the characteristics of RNA interference (RNAi) is systemic spread of the silencing signal among cells and tissues throughout the organism. Systemic RNAi, initiated by double-stranded RNA (dsRNA) ingestion, has been reported in diverse invertebrates, including honey bees, demonstrating environmental RNA uptake that undermines homologous gene expression. However, the question why any organism would take up RNA from the environment has remained largely unanswered. Here, we report on horizontal RNA flow among honey bees mediated by secretion and ingestion of worker and royal jelly diets. We show that ingested dsRNA spreads through the bees hemolymph associated with a protein complex. The systemic dsRNA is secreted with the jelly and delivered to larvae via ingestion. Furthermore, we demonstrate that transmission of jelly-secreted dsRNA to larvae is biologically active and triggers gene knockdown that lasts into adulthood. Finally, RNA extracted from worker and royal jellies harbor differential naturally occurring RNA populations. Some of these RNAs corresponded to honey bee protein coding genes, transposable elements, non-coding RNA and exogenous viruses. These results reveal an inherent property of honey bees to share RNA among individuals and generations. Thus, our findings suggest a transmissible RNA pathway, playing a role in social immunity and epigenetic dynamics among honey bees and potentially other closely interacting organisms.\n\nSIGNIFICANCEHoney bees are eusocial insects, living in a colony that is often described as a superorganism. RNA mobility among cells of an organism has been documented in plants and animals. Here we show that RNA spreads further in honey bees, and is horizontally transferred between individuals and across generations. We found that honey bees share biologically active RNA through secretion and ingestion of worker and royal jellies. Such RNA initiated RNA interference, which is a known defense mechanism against viral infection. Furthermore, we characterized diverse RNA profiles of worker and royal jelly, including fragmented viral RNA. Our findings demonstrate a transmissible RNA pathway with potential roles in social immunity and epigenetic signaling among members of the hive.",2018-08-09,"Maori, E.; Garbian, Y.; Kunik, V.; Mozes-Koch, R.; Malka, O.; Kalev, H.; Sabath, N.; Sela, I.; Shafir, S.",,,,True
64478db449af8e4a5645c17f548649a0159da0c6,biorxiv,Individual and temporal variation in pathogen load predicts long-term impacts of an emerging infectious disease,doi.org/10.1101/392324,,,See https://www.biorxiv.org/about-biorxiv,"Emerging infectious diseases increasingly threaten wildlife populations. Most studies focus on managing short-term epidemic properties, such as controlling early outbreaks. Predicting long-term endemic characteristics with limited retrospective data is more challenging. We used individual-based modelling informed by individual variation in pathogen load and transmissibility to predict long-term impacts of a lethal, transmissible cancer on Tasmanian devil (Sarcophilus harrisii) populations. For this, we employed Approximate Bayesian Computation to identify model scenarios that best matched known epidemiological and demographic system properties derived from ten years of data after disease emergence, enabling us to forecast future system dynamics. We show that the dramatic devil population declines observed thus far are likely attributable to transient dynamics. Only 21% of matching scenarios led to devil extinction within 100 years following devil facial tumour disease (DFTD) introduction, whereas DFTD faded out in 57% of simulations. In the remaining 22% of simulations, disease and host coexisted for at least 100 years, usually with long-period oscillations. Our findings show that pathogen extirpation or host-pathogen coexistence are much more likely than the DFTD-induced devil extinction, with crucial management ramifications. Accounting for individual-level disease progression and the long-term outcome of devil-DFTD interactions at the population-level, our findings suggest that immediate management interventions are unlikely to be necessary to ensure the persistence of Tasmanian devil populations. This is because strong population declines of devils after disease emergence do not necessarily translate into long-term population declines at equilibria. Our modelling approach is widely applicable to other host-pathogen systems to predict disease impact beyond transient dynamics.",2018-08-15,"Wells, K.; Hamede, R. K.; Jones, M. E.; Hohenlohe, P. A.; Storfer, A.; McCallum, H. I.",,,,True
e4e5e67fd4f75548dffab7f75484bc14fa15c0c2,biorxiv,Existing host range mutations constrain further emergence of RNA viruses,doi.org/10.1101/394080,,,See https://www.biorxiv.org/about-biorxiv,"RNA viruses are capable of rapid host shifting, typically due to a point mutation that confers expanded host range. As additional point mutations are necessary for further expansions, epistasis among host range mutations can potentially affect the mutational neighborhood and frequency of niche expansion. We mapped the mutational neighborhood of host range expansion using three genotypes of the dsRNA bacteriophage phi6 (wildtype and two isogenic host range mutants) on the novel host Pseudomonas syringae pv. atrofaciens (PA). Sanger sequencing of fifty PA mutant clones for each genotype and population Illumina sequencing both revealed the same high frequency mutations allowing infection of PA. Wildtype phi6 had at least nine different ways of mutating to enter the novel host, eight of which are in p3 (host attachment protein gene), and 13/50 clones had unchanged p3 genes. However, the two isogenic mutants had dramatically restricted neighborhoods: only one or two mutations, all in p3. Deep sequencing revealed that wildtype clones without mutations in p3 likely had changes in p12 (morphogenic protein), a region that was not polymorphic for the two isogenic host range mutants. Sanger sequencing confirmed that 10/13 of the wildtype phi6 clones had nonsynonymous mutations in p12 and two others had point mutations in p9 and p5 - none of these genes had previously been associated with host range expansion in phi6. We demonstrate, for the first time, epistatic constraint in an RNA virus due to host range mutations themselves, which has implications for models of serial host range expansion.\n\nImportanceRNA viruses mutate rapidly and frequently expand their host ranges to infect novel hosts, leading to serial host shifts. Using an RNA bacteriophage model system (Pseudomonas phage phi6), we studied the impact of pre-existing host range mutations on another host range expansion. Results from both clonal Sanger and Illumina sequencing show extant host range mutations dramatically narrow the neighborhood of potential host range mutations compared to wildtype phi6. This research suggests that serial host shifting viruses may follow a small number of molecular paths to enter additional novel hosts. We also identified new genes involved in phi6 host range expansion, expanding our knowledge of this important model system in experimental evolution.",2018-08-17,"Zhao, L.; Seth Pasricha, M.; Stemate, D.; Crespo-Bellido, A.; Gagnon, J.; Duffy, S.",,,,True
ebb553a859d31ebcfc57d489ca84af0df894dab8,biorxiv,Choanoflagellate transfection illuminates their cell biology and the ancestry of animal septins,doi.org/10.1101/343111,,,See https://www.biorxiv.org/about-biorxiv,"As the closest living relatives of animals, choanoflagellates offer unique insights into animal origins and core mechanisms underlying animal cell biology. However, unlike traditional model organisms, such as yeast, flies and worms, choanoflagellates have been refractory to DNA delivery methods for expressing foreign genes. Here we report the establishment of a robust method for expressing transgenes in the choanoflagellate Salpingoeca rosetta, overcoming barriers that have previously hampered DNA delivery and expression. To demonstrate how this method accelerates the study of S. rosetta cell biology, we engineered a panel of fluorescent protein markers that illuminate key features of choanoflagellate cells. We then investigated the localization of choanoflagellate septins, a family of GTP-binding cytoskeletal proteins that are hypothesized to regulate the multicellular rosette development in S. rosetta. Fluorescently tagged septins localized to the basal pole of S. rosetta single cells and rosettes in a pattern resembling septin localization in animal epithelia. The establishment of transfection in S. rosetta and its application to the study of septins represent critical advances in the growth of S. rosetta as an experimental model for investigating choanoflagellate cell biology, core mechanisms underlying animal cell biology, and the origin of animals.",2018-08-20,"Booth, D.; Middleton, H.; King, N.",,,,True
837c77d566651f559ed3f78c2e490213f99212e6,biorxiv,The geometry of dependence: solitary bee larvae prioritize carbohydrate over protein in parentally provided pollen,doi.org/10.1101/397802,,,See https://www.biorxiv.org/about-biorxiv,"O_LIBees, important pollinators, have declined significantly in recent decades, and human- induced changes to nutritional landscapes are partly responsible. Changes to nutritional quality rather than quantity have been overlooked as a threat to bee health. Yet knowledge of bee nutrition is currently largely restricted to adults of social species. Larval stages, where most growth occurs, are relatively understudied - perhaps because most social bees provision progressively and collectively, making nutrition difficult to trace.\nC_LIO_LIIn mass-provisioning solitary bees (Osmia bicornis L.), we can manipulate and follow larval nutrition, and thereby determine effects of changes in diet quality. Under the Geometric Framework for Nutrition, we restricted larvae to 6 diets: 3 protein:carbohydrate ratios and 2 nutrient concentrations. We asked: (a) which diets maximise body size and survival, (b) what consumption rules do larvae follow when nutrients are imbalanced? Finally, (c) given a choice of complementary diets, are larvae able to select a dietary balance?\nC_LIO_LILarvae pupated after consuming a fixed carbohydrate amount, but tolerated a wide range of protein. Body size and survival were maximised on our lowest P:C ratio diet, and having consumed the most carbohydrate. When eating freely from two diets, larvae converged on a P:C ratio of 1:1.8, but not an overall nutrient intake target. Nevertheless, larvae maintained stable carbohydrate intake, while protein intake varied with the available diet.\nC_LIO_LIOur results suggest solitary bee larvae regulate carbohydrate most closely, but that excessive indigestible material may limit their actual nutrient intake. Carbohydrate may be critical to overwinter survival, and/or may be more limiting than protein. The large variation in protein tolerated, despite its importance, suggests bee larvae may be vulnerable to landscape changes - and therefore reliant on parents to regulate protein. Given the mixed evidence on whether parents can sense pollen protein content, our results highlight bees potential vulnerability to a \""nutritional trap\"", i.e. where rapid changes in their nutritional environment outstrip their evolved capacity to detect those changes, impairing their fitness.\nC_LI",2018-08-22,"Austin, A. J.; Gilbert, J. D. J.",,,,True
975349ac1c79fc64525ee17e7d088c88c2c2071b,biorxiv,A practical generation interval-based approach to inferring the strength of epidemics from their speed,doi.org/10.1101/312397,,,See https://www.biorxiv.org/about-biorxiv,"Infectious-disease outbreaks are often characterized by the reproductive number and exponential rate of growth r. provides information about out-break control and predicted final size. Directly estimating is difficult, while r can often be estimated from incidence data. These quantities are linked by the generation interval - the time between when an individual is infected by an infector, and when that infector was infected. It is often infeasible to ob-tain the exact shape of a generation-interval distribution, and to understand how this shape affects estimates of . We show that estimating generation interval mean and variance provides insight into the relationship between and r. We use examples based on Ebola, rabies and measles to explore approximations based on gamma-distributed generation intervals, and find that use of these simple approximations are often sufficient to capture the r- relationship and provide robust estimates of .",2018-08-27,"Park, S. W.; Champredon, D.; Weitz, J.; Dushoff, J.",,,,True
c3e5af129cd3332c6a01776cbb9534bceb46e21a,biorxiv,"GI-16 lineage (624/I or Q1), there and back again: the history of one of the major threat for poultry farming of our era",doi.org/10.1101/402800,,,See https://www.biorxiv.org/about-biorxiv,"The genetic variability of Infectious bronchitis virus (IBV) is one of the main challenges for its control, hindering not only the development of effective vaccination strategies but also its classification and, consequently, epidemiology understanding. The 624/I and Q1 genotypes, now recognized to be part of the GI-16 lineage, represent an excellent example of the practical consequences of IBV molecular epidemiology limited knowledge. In fact, being their common origin unrecognized for a long time, independent epidemiological pictures were drawn for the two genotypes. To fix this misinterpretation, the present study reconstructs the history, population dynamics and spreading patterns of GI-16 lineage as a whole using a phylodynamic approach. A collection of worldwide available hypervariable region 1 and 2 (HVR12) and 3 (HVR3) sequences of the S1 protein was analysed together with 258 HVR3 sequences obtained from samples collected in Italy (the country where this genotype was initially identified) since 1963. The results demonstrate that after its emergence at the beginning of the XX century, GI-16 was able to persist until present days in Italy. Approximately in the late 1980s, it migrated to Asia, which became the main nucleus for further spreading to Middle East, Europe and especially South America, likely through multiple introduction events. A remarkable among-country diffusion was also demonstrated in Asia and South America. Interestingly, although most of the recent Italian GI-16 strains originated from ancestral viruses detected in the same country, a couple were closely related to Chinese ones, supporting a backward viral flow from China to Italy.\n\nBesides to the specific case-study results, this work highlights the misconceptions that originate from the lack of a unified nomenclature and poor molecular epidemiology data generation and sharing. This shortcoming appears particularly relevant since the described scenario could likely be shared by many other IBV genotypes and pathogens in general.",2018-08-28,"Moreno, A.; Franzo, G.; Cecchinato, M.; Tosi, G.; Fiorentini, L.; Faccin, F.; Tucciarone, C. M.; Trogu, T.; Barbieri, I.; Massi, P.",,,,True
b3cb1d91dcd7f78dd9bbc88b93d2403eb6869746,biorxiv,Genetic control of the HDL proteome,doi.org/10.1101/405811,,,See https://www.biorxiv.org/about-biorxiv,"High-density lipoproteins (HDL) are nanoparticles with >80 associated proteins, phospholipids, cholesterol and cholesteryl esters. A comprehensive genetic analysis of the regulation of proteome of HDL isolated from a panel of 100 diverse inbred strains of mice, Hybrid Mouse Diversity Panel (HMDP), revealed widely varied HDL protein levels across the strains. Some of this variation was explained by local, cis-acting regulation, termed cis-protein quantitative trait loci. Variations in apolipoprotein A-II and apolipoprotein C-3 affected the abundance of multiple HDL proteins indicating a coordinated regulation. We identified modules of co-varying proteins and define a protein-protein interaction network describing the protein composition of the naturally occurring subspecies of HDL in mice. Sterol efflux capacity varied up to 3-fold across the strains and HDL proteins displayed distinct correlation patterns with macrophage and ABCA1 specific cholesterol efflux capacity and cholesterol exchange, suggesting that subspecies of HDL participate in discrete functions. The baseline and stimulated sterol efflux capacity phenotypes associated with distinct QTLs with smaller effect size suggesting a multi genetic regulation. Our results highlight the complexity of HDL particles by revealing high degree of heterogeneity and intercorrelation, some of which is associated with functional variation, supporting the concept that HDL-cholesterol alone is not an accurate measure of HDLs properties such as protection against CAD.",2018-08-31,"Pamir, N.; Pan, C.; Plubell, D. L.; Hutchins, P. M.; Tang, C.; Wimberger, J.; Irwin, A.; Vallim, T. Q. d. A.; Heinecke, J. W.; Lusis, A. J.",,,,True
1983cbc32412a9a7b1601b6778605f9e98ab69e0,biorxiv,Glycosyltransferases promote development and prevent promiscuous cell aggregation in the choanoflagellate S. rosetta,doi.org/10.1101/384453,,,See https://www.biorxiv.org/about-biorxiv,"The mechanisms underlying multicellular development in the animal stem lineage may be reconstructed through the study of choanoflagellates, the closest living relatives of animals. To determine the genetic underpinnings of multicellularity in the emerging model choanoflagellate S. rosetta, we performed a screen for mutants with defects in multicellular rosette development. In two of the mutants, Jumble and Couscous, single cells failed to develop into orderly rosettes but instead aggregated promiscuously into amorphous clumps of cells. Both mutants mapped to lesions in genes encoding glycosyltransferases and the mutations perturbed glycosylation patterns in the extracellular matrix (ECM). In animals, glycosyltransferases transfer activated sugars to donor molecules and thereby sculpt the polysaccharide-rich ECM, regulate integrin and cadherin activity, and, when disrupted, contribute to tumorigenesis. The finding that glycosyltransferases promote proper rosette development and prevent cell aggregation in S. rosetta suggests a pre-metazoan role for glycosyltransferases in regulating development and preventing abnormal tumor-like multicellularity.\n\nIMPACT STATEMENTA genetic screen reveals that glycosyltransferases are required for proper rosette development and the prevention of cell clumping in one of the closest living relatives of animals, the choanoflagellate S. rosetta.",2018-08-31,"Wetzel, L.; Levin, T.; Hulett, R. E.; Chan, D.; King, G.; Aldayafleh, R.; Booth, D.; Sigg, M. A.; King, N.",,,,True
5a843f4299b04090ff76451decfe9f0b025cfe48,biorxiv,Capturing diverse microbial sequence with comprehensive and scalable probe design,doi.org/10.1101/279570,,,See https://www.biorxiv.org/about-biorxiv,"Metagenomic sequencing has the potential to transform microbial detection and characteri zation, but new tools are needed to improve its sensitivity. We developed CATCH (Compact Aggregation of Targets for Comprehensive Hybridization), a computational method to enhance nucleic acid capture for enrichment of diverse microbial taxa. CATCH designs compact probe sets that achieve full coverage of known sequence diversity and that scale well with this diversity. To illustrate applications of CATCH, we focused on capturing viral genomes. We designed, synthesized, and validated multiple probe sets, including one that targets whole genomes of the 356 viral species known to infect humans. Capture with these probe sets enriched unique viral content on average 18x and allowed us to assemble genomes that we could not otherwise recover, while accurately preserving within-sample diversity. We used this approach to recover genomes from the 2018 Lassa fever outbreak in Nigeria and to improve detection of viral infections in samples with unknown content. Together, this work demonstrates a path toward more sensitive, cost-effective metagenomic sequencing.",2018-09-03,"Metsky, H. C.; Siddle, K. J.; Gladden-Young, A.; Qu, J.; Yang, D. K.; Brehio, P.; Goldfarb, A.; Piantadosi, A.; Wohl, S.; Carter, A.; Lin, A. E.; Barnes, K. G.; Tully, D. C.; Corleis, B.; Hennigan, S.; Barbosa-Lima, G.; Vieira, Y. R.; Paul, L. M.; Tan, A. L.; Garcia, K. F.; Parham, L. A.; Odia, I.; Eromon, P.; Folarin, O. A.; Goba, A.; Viral Hemorrhagic Fever Consortium,  ; Simon-Loriere, E.; Hensley, L.; Balmaseda, A.; Harris, E.; Kwon, D.; Allen, T. M.; Runstadler, J. A.; Smole, S.; Bozza, F. A.; Souza, T. M.; Isern, S.; Michael, S. F.; Lorenzana, I.; Gehrke, L.; Bosch, I.; Ebel, G.; Grant, ",,,,True
380a4d07d22910246c6f189fd2da93b270b96981,biorxiv,Large-scale analysis of redox-sensitive conditionally disordered protein regions reveal their widespread nature and key roles in high-level eukaryotic processes,doi.org/10.1101/412692,,,See https://www.biorxiv.org/about-biorxiv,"Recently developed quantitative redox proteomic studies enable the direct identification of redox-sensing cysteine residues that regulate the functional behavior of target proteins in response to changing levels of reactive oxygen species (ROS). At the molecular level, redox regulation can directly modify the active sites of enzymes, although a growing number of examples indicate the importance of an additional underlying mechanism that involves conditionally disordered proteins. These proteins alter their functional behavior by undergoing a disorder-to-order transition in response to changing redox conditions. However, the extent to which this mechanism is used in various proteomes is currently unknown. Here, we use a recently developed sequence-based prediction tool incorporated into the IUPred2A web server to estimate redox-sensitive conditionally disordered regions on a large scale. We show that redox-sensitive conditional disorder is fairly widespread in various proteomes and that its presence strongly correlates with the expansion of specific domains in multicellular organisms that largely rely on extra stability provided by disulfide bonds or zinc ion binding. The analyses of yeast redox proteomes and human disease data further underlie the significance of this phenomenon in the regulation of a wide range of biological processes, as well as its biomedical importance.",2018-09-10,"Erdos, G.; Meszaros, B.; Reichmann, D.; Dosztanyi, Z.",,,,True
ac81102667b0d56edeb8ab0044765dc49a19f374,biorxiv,Determination of host cell proteins constituting the molecular microenvironment of coronavirus replicase complexes by proximity-labeling,doi.org/10.1101/417907,,,See https://www.biorxiv.org/about-biorxiv,"Positive-sense RNA viruses hijack intracellular membranes that provide niches for viral RNA synthesis and a platform for interactions with host proteins. However, little is known about host factors at the interface between replicase complexes and the host cytoplasm. We engineered a biotin ligase into a coronaviral replication/transcription complex (RTC) and identified >500 host proteins constituting the RTC microenvironment. siRNA-silencing of each RTC-proximal host factor demonstrated importance of vesicular trafficking pathways, ubiquitin-dependent and autophagy-related processes, and translation initiation factors. Notably, detection of translation initiation factors at the RTC was instrumental to visualize and demonstrate active translation proximal to replication complexes of several coronaviruses.\n\nCollectively, we establish a spatial link between viral RNA synthesis and diverse host factors of unprecedented breadth. Our data may serve as a paradigm for other positive-strand RNA viruses and provide a starting point for a comprehensive analysis of critical virus-host interactions that represent targets for therapeutic intervention.",2018-09-14,"V'kovski, P.; Gerber, M.; Kelly, J.; Pfaender, S.; Ebert, N.; Braga Lagache, S.; Simillion, C.; Portmann, J.; Stalder, H.; Gaschen, V.; Bruggmann, R.; Stoffel, M.; Heller, M.; Dijkman, R.; Thiel, V.",,,,True
bf04c9ddc80690a5e2d3c74d79a797319e36e5b6,biorxiv,Exploring the Binding Mechanism between Human Profilin (PFN1) and Polyproline-10 through Binding Mode Screening,doi.org/10.1101/418830,,,See https://www.biorxiv.org/about-biorxiv,"The large magnitude of protein-protein interaction (PPI) pairs within the human interactome necessitates the development of predictive models and screening tools to better understand this fundamental molecular communication. However, despite enormous efforts from various groups to develop predictive techniques in the last decade, PPI complex structures are in general still very challenging to predict due to the large number of degrees of freedom. In this study, we use the binding complex of human profilin (PFN1) and polyproline-10 (P10) as a model system to examine various approaches, with the aim of going beyond normal protein docking for PPI prediction and evaluation. The potential of mean force (PMF) was first obtained from the timeconsuming umbrella sampling, which confirmed that the most stable binding structure identified by the maximal PMF difference is indeed the crystallographic binding structure. Moreover, crucial residues previously identified in experimental studies, W3, H133 and S137 of PFN1, were found to form favorable hydrogen bonds with P10, suggesting a zipping process during the binding between PFN1 and P10. We then explored both regular molecular dynamics (MD) and steered molecular dynamics (SMD) simulations, seeking for better criteria of ranking the PPI prediction. Despite valuable information obtained from conventional MD simulations, neither the commonly used interaction energy between the two binding parties nor the long-term root mean square displacement (RMSD) correlates well with the PMF results. On the other hand, with a sizable collection of trajectories, we demonstrated that the average rupture work calculated from SMD simulations correlates fairly well with the PMFs (R2 = 0.67), making it a promising PPI screening method.",2018-09-16,"Zhang, L.; Bell, D. R.; Luan, B.; Zhou, R.",,,,True
f1806d65f8bf2102f47a9a861d57ca3a765f617d,biorxiv,VAPiD: a lightweight cross platform viral annotation pipeline and identification tool to facilitate virus genome submissions to NCBI GenBank,doi.org/10.1101/420463,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundWith sequencing technologies becoming cheaper and easier to use, more groups are able to obtain whole genome sequences of viruses of public health and scientific importance. Submission of genomic data to NCBI GenBank is a requirement prior to publication and plays a critical role in making scientific data publicly available.\n\nGenBank currently has automatic prokaryotic and eukaryotic genome annotation pipelines but has no viral annotation pipeline beyond influenza virus. Annotation and submission of viral genome sequence is a non-trivial task, especially for groups that do not routinely interact with GenBank for data submissions.\n\nResultsWe present Viral Annotation Pipeline and iDentification (VAPiD), a portable and lightweight command-line tool for annotation and GenBank deposition of viral genomes. VAPiD supports annotation of nearly all unsegmented viral genomes. The pipeline has been validated on human immunodeficiency virus, human parainfluenza virus 1-4, human metapneumovirus, human coronaviruses (229E/OC43/NL63/HKU1/SARS/MERS), human enteroviruses/rhinoviruses, measles virus, mumps virus, Hepatitis A-E Virus, Chikungunya virus, dengue virus, and West Nile virus, as well the human polyomaviruses BK/JC/MCV, human adenoviruses, and human papillomaviruses. The program can handle individual or batch submissions of different viruses to GenBank and correctly annotates multiple viruses, including those that contain ribosomal slippage or RNA editing without prior knowledge of the virus to be annotated. VAPiD is programmed in Python and is compatible with Windows, Linux, and Mac OS systems.\n\nConclusionsWe have created a portable, lightweight, user-friendly, internet-enabled, open-source, command-line genome annotation and submission package to facilitate virus genome submissions to NCBI GenBank. Instructions for downloading and installing VAPiD can be found at https://github.com/rcs333/VAPiD.",2018-09-18,"Shean, R. C.; Makhsous, N.; Stoddard, G. D.; Lin, M. J.; Greninger, A. L.",,,,False
228edf7f7e53e88e246fc77b7b7664ac35d7278e,biorxiv,Distinct spread of DNA and RNA viruses among mammals amid prominent role of domestic species,doi.org/10.1101/421511,,,See https://www.biorxiv.org/about-biorxiv,"Emerging infectious diseases arising from pathogen spillover from mammals to humans comprise a substantial health threat. Tracing virus origin and predicting the most likely host species for future spillover events are major objectives in One Health disciplines. However, the species that share pathogens most widely with other mammals, and the role of different wildlife groups in sharing viruses with humans remain poorly identified. To address this challenge, we applied network analysis and Bayesian hierarchical models to a global database of mammal-virus associations. We show that domesticated mammals and some primates hold the most central positions in networks of known mammal-virus associations. We revealed strong evidence that DNA viruses were phylogenetically more host specific than RNA viruses, while the frequencies of sharing viruses among hosts and the proportion of zoonotic viruses in hosts were larger for RNA than DNA viruses. Among entire host-virus networks, Carnivora and Chiroptera hold central positions for mainly sharing RNA viruses with other host species, while network centrality of Primates scored relatively high for sharing DNA viruses. Ungulates hold central positions for sharing both RNA and DNA viruses. Acknowledging the role of domestic species in addition to host and virus traits in patterns of virus sharing is necessary to improve our understanding of virus spread and spillover in times of global change.",2018-09-19,"Wells, K.; Morand, S.; wardeh, m.; Baylis, M.",,,,True
2c18d80cfc792faa3d6e35c72d4b6b58ee93fdad,biorxiv,Multiplex logic processing isothermal diagnostic assays for an evolving virus,doi.org/10.1101/424440,,,See https://www.biorxiv.org/about-biorxiv,"We have developed a generalizable  smart molecular diagnostic capable of accurate point-of-care (POC) detection of variable nucleic acid targets. Our one-pot isothermal assay relies on multiplex execution of four loop-mediated isothermal amplification reactions, with primers that are degenerate and redundant, thereby increasing the breadth of targets while reducing the probability of amplification failure. An easy-to-read visual answer is computed directly by a multi-input Boolean OR gate signal transducer that uses degenerate strand exchange probes to assess any combination of amplicons. We demonstrate our platform by using the same assay to detect divergent Asian and African lineages of the evolving Zika virus (ZIKV), while maintaining selectivity against non-target viruses. Direct analysis of biological specimens proved possible, with 20 virions / {micro}l being directly detected in human saliva within 90 minutes, and crudely macerated ZIKV-infected Aedes aegypti mosquitoes being identified with 100% specificity and sensitivity. The ease-of-use with minimal instrumentation, broad programmability, and built-in fail-safe reliability make our smart molecular diagnostic attractive for POC use.",2018-09-23,"Bhadra, S.; Saldana, M. A.; Han, H. G.; Hughes, G. L.; Ellington, A. D.",,,,True
9d552fa1dc2e4d9302bc61c57c6c4c62c541a03e,biorxiv,"Changes in mRNA abundance drive differential shuttling of RNA binding proteins, linking cytoplasmic RNA degradation to transcription",doi.org/10.1101/295972,,,See https://www.biorxiv.org/about-biorxiv,"Alterations in global mRNA decay broadly impact multiple stages of gene expression, although signals that connect these processes are incompletely defined. Here, we used tandem mass tag labeling coupled with mass spectrometry to reveal that changing the mRNA decay landscape, as frequently occurs during viral infection, results in subcellular redistribution of RNA binding proteins (RBPs) in human cells. Accelerating Xrn1-dependent mRNA decay through expression of a gammaherpesviral endonuclease drove nuclear translocation of many RBPs, including poly(A) tail-associated proteins. Conversely, cells lacking Xrn1 exhibited changes in the localization or abundance of numerous factors linked to mRNA turnover. Using these data, we uncovered a new role for relocalized cytoplasmic poly(A) binding protein in repressing recruitment of TATA binding protein and RNA polymerase II to promoters. Collectively, our results show that changes in cytoplasmic mRNA decay can directly impact protein localization, providing a mechanism to connect seemingly distal stages of gene expression.",2018-09-25,"Gilbertson, S.; Federspiel, J. D.; Hartenian, E.; Cristea, I. M.; Glaunsinger, B.",,,,False
50ed5cabf8d74c2a700184f876ad15de2239adfa,biorxiv,An anti-Gn glycoprotein antibody from a convalescent patient potently inhibits the infection of severe fever with thrombocytopenia syndrome virus,doi.org/10.1101/434530,,,See https://www.biorxiv.org/about-biorxiv,"Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease localized to China, Japan, and Korea that is characterized by severe hemorrhage and a high fatality rate. Currently, no specific vaccine or treatment has been approved for this disease. To develop a therapeutic agent for SFTS, we isolated antibodies from a phage-displayed antibody library that was constructed from a patient who recovered from SFTS virus (SFTSV) infection. One antibody, designated as Ab10, was reactive to the Gn envelope glycoprotein of SFTSV and protected host cells and A129 mice from infection in both in vitro and in vivo experiments. Notably, Ab10 protected 80% of mice, even when injected 5 days after inoculation with a lethal dose of SFTSV. Using cross-linker assisted mass spectrometry and alanine scanning, we located the non-linear epitope of Ab10 on the Gn glycoprotein domain II and an unstructured stem region, suggesting that Ab10 may inhibit a conformational alteration that is critical for cell membrane fusion between the virus and host cell. Ab10 reacted to recombinant Gn glycoprotein in Gangwon/Korea/2012, HB28, and SD4 strains. Additionally, based on its epitope, we predict that Ab10 binds the Gn glycoprotein in 247 of 272 reported SFTSV isolates previously reported. Together, these data suggest that Ab10 has potential to be developed into a therapeutic agent that could protect against more than 90% of reported SFTSV isolates.\n\nAuthor summarySevere fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease localized to China, Japan, and Korea. This tick-borne virus has infected more than 5,000 humans with a 6.4% to 20.9% fatality rate. Currently, there are no prophylactic or therapeutic measures against this virus. Historically, antibodies from patients who recovered from viral infection have been used to treat new patients. Until now, one recombinant monoclonal antibody was approved for the prophylaxis of respiratory syntial virus infection. We selected 10 antibodies from a patient who recovered from SFTS and found that one antibody potently inhibited SFTS viral infection in both test tube and animal studies. We determined the binding site of this antibody to SFTS virus, which allowed us to predict that this antibody could bind 247 out of 272 SFTS virus isolates reported up to now. We anticipate that this antibody could be developed into a therapeutic measure against SFTS.",2018-10-03,"Kim, K. H.; Kim, J.; Ko, M.; Chun, J. Y.; Kim, H.; Kim, S.; Min, J.-Y.; Park, W. B.; Oh, M.-d.; Chung, J.",,,,True
ac4a3bbe27272cd6780e7168906b0bf1413fc749,biorxiv,Innate Immune Priming by cGAS as a Preparatory Countermeasure Against RNA Virus Infection,doi.org/10.1101/434027,,,See https://www.biorxiv.org/about-biorxiv,"The detection of nucleic acids by pattern recognition receptors is an ancient and conserved component of the innate immune system. Notably, RNA virus genomes are sensed by mammalian cytosolic RIG-I-like receptors, thereby activating interferon-stimulated gene (ISG) expression to restrict viral replication. However, recent evidence indicates that the cGAS-STING DNA sensing pathway also protects against RNA viruses. So far, the mechanisms responsible for DNA sensing of RNA viruses, which replicate without known DNA intermediates, remain unclear. By using cGAS gene knockout and reconstitution in human and mouse cell cultures, we discovered that DNA sensing and cGAMP synthase activities are required for cGAS-mediated restriction of vesicular stomatitis virus and Sindbis virus. The level of cGAMP produced in response to RNA virus infection was below the threshold of detection, suggesting that only transient and/or low levels of cGAMP are produced during RNA virus infections. To clarify the DNA ligands that activate cGAS activity, we confirmed that cGAS binds mitochondrial DNA in the cytosol of both uninfected and infected cells; however, the amount of cGAS-associated mitochondrial DNA did not change in response to virus infection. Rather, a variety of pre-existing cytosolic DNAs, including mitochondrial DNA and endogenous cDNAs, may serve as stimuli for basal cGAS activation. Importantly, cGAS knockout and reconstitution experiments demonstrated that cGAS drives low-level ISG expression at steady state. We propose that cGAS-STING restricts RNA viruses by promoting a preparatory immune activation state within cells, likely primed by endogenous cellular DNA ligands.\n\nImportanceMany medically important RNA viruses are restricted by the cGAS-STING DNA-sensing pathway of innate immune activation. Since these viruses replicate without DNA intermediates, it is unclear what DNA ligand(s) are responsible for triggering this pathway. We show here that cGASs DNA binding and signaling activities are required for RNA virus restriction, similar to the mechanisms by which it restricts DNA viruses. Furthermore, we confirmed that cGAS continuously binds host DNA, which was unaffected by RNA virus infection. Finally, cGAS expression correlated with the low-level expression of interferon-stimulated genes in uninfected cells, both in vitro and in vivo. We propose that cGAS-mediated sensing of endogenous DNA ligands contributes to RNA virus restriction by establishing a baseline of innate immune activation.",2018-10-03,"Parker, M. T.; Gopinath, S.; Perez, C. E.; Linehan, M. M.; Crawford, J.; Iwasaki, A.; Lindenbach, B. D.",,,,True
760481ce5a46e6efa12a80202bbd240dcbefa8fd,biorxiv,Evaluating an Upper Respiratory Disease Panel on the Portable MinION Sequencer,doi.org/10.1101/436600,,,See https://www.biorxiv.org/about-biorxiv,"The MinION was used to evaluate upper respiratory disease infections using both whole genome amplification (WGA), targeted sequencing, and was found to have tremendous potential for field use. The MinION nanopore sequencer was been released to community testers for evaluation using a variety of sequencing applications. The MinION was used to evaluate upper respiratory disease infections using both whole genome amplification and targeted sequencing, and was found to have tremendous potential for field use. In this study, we tested the ability of the MinION nanopore sequencer to accurately identify and differentiate clinical bacterial and viral samples via targeted sequencing and whole genome sequencing. The current nanopore technology has limitations with respect to error rate but has steadily improved with development of new flow cells and kits. Upper respiratory disease organisms were successfully identified and differentiated down to the strain level with 87-98% alignment to our reference genome database. The ability to differentiate strains by amplicon and whole genome sequencing on the MinION was accomplished despite the observed average per 100-base error rate averaged 1.2E-01. This study offers evidence of the utility of sequencing to identify and differentiate both viral and bacterial species present within clinical samples.",2018-10-05,"Lyon, W. J.; Smith, Z. K.; Geier, B.; Baldwin, J. C.; Starr, C. R.",,,,True
0a43046c154d0e521a6c425df215d90f3c62681e,biorxiv,"Comparisons of a Novel Air Sampling Filter Material, Wash Buffers and Extraction Methods in the Detection and Quantification of Influenza Virus",doi.org/10.1101/441154,,,See https://www.biorxiv.org/about-biorxiv,"Quantification of aerosolized influenza virus is used for determining inhalation exposure. Several bioaerosol samplers and analytical methods have been used; however, the detection and quantification of influenza virus among aerosol samples remains challenging. Therefore, improved viral aerosol measurement methods are needed. This study evaluated influenza virus recovery among three filter types polytetrafluoroethylene, polyvinylchloride and polystyrene. Polytetrafluoroethylene, polyvinylchloride are fabricated filter materials and commonly used in the scientific literature to sample for viral aerosols. A novel, electrospun polystyrene filter material may improve viral aerosol recovery during filter-based air sampling. The filter materials were compared across the following conditions: treated with or without air, filter wash buffer (HBSS or PBS), and viral RNA extraction method (QIAamp Viral RNA Mini Kit or Trizol). Twenty trials were completed in a chamber and samples were analyzed using RT-qPCR. Viral recovery was significantly different (p-value < .0001) by filter type. Polystyrene filter use resulted in recovery of the most viral RNA. Air sampling did not affect the recovery of viral RNA from the filter materials (p-values > 0.05). Viral RNA concentrations were significantly different across extraction methods for all comparisons (p-values < 0.05). Our results demonstrated that the novel polystyrene filter material resulted in the highest concentration of extracted RNA compared to the commonly used polytetrafluoroethylene and polyvinylchloride, which we speculate may be related to the chemical composition of the filter material (e.g., polystyrene is an aromatic hydrocarbon whereas polytetrafluoroethylene and polyvinylchloride contain more polar, and thus potentially reactive, carbon-halogen bonds). Air sampling did not have an effect on viral RNA recovery. Using Hanks Balanced Salt Solution with QIAamp Viral RNA Mini Kit, and Phosphate-buffered saline with the Trizol extraction, resulted in the most viral RNA recovery.",2018-10-11,"Thedell, T.; Boles, C. L.; Cwiertny, D. W.; Brown, G. D.; Qian, J.; Nonnenmann, M. W.",,,,True
f6312e7233ad4c0780492db3c05a61abe4fb6b22,biorxiv,The Infectious Bronchitis Virus Coronavirus Envelope Protein Alters Golgi pH to Protect Spike Protein and Promote Release of Infectious Virus,doi.org/10.1101/440628,,,See https://www.biorxiv.org/about-biorxiv,"Coronaviruses (CoVs) are important human pathogens with significant zoonotic potential. Progress has been made toward identifying potential vaccine candidates for highly pathogenic human CoVs, including use of attenuated viruses that lack the CoV envelope (E) protein or express E mutants. However, no approved vaccines or anti-viral therapeutics exist. CoVs assemble by budding into the lumen of the early Golgi prior to exocytosis. The small CoV E protein plays roles in assembly, virion release, and pathogenesis. CoV E has a single hydrophobic domain (HD), is targeted to Golgi membranes, and has cation channel activity in vitro. The E protein from the avian infectious bronchitis virus (IBV) has dramatic effects on the secretory system, which requires residues in the HD. Mutation of the HD of IBV E during infection results in impaired growth kinetics, impaired release of infectious virions, accumulation of IBV S protein on the plasma membrane when compared IBV WT infected cells, and aberrant cleavage of IBV S on the surface of virions. We previously reported the formation of two distinct oligomeric pools of IBV E in transfected and infected cells. Disruption of the secretory pathway by IBV E correlates with a form that is likely monomeric, suggesting that the effects on the secretory pathway are independent of E ion channel activity. Here, we present evidence suggesting that the monomeric form of IBV E correlates with a rise in the pH of the Golgi lumen. We demonstrate that infection with IBV induces neutralization of Golgi luminal pH, promoting a model in which IBV E alters the secretory pathway through interaction with host cells factors, protecting IBV spike protein (S) from premature cleavage and leading to the efficient release of infectious virus from the cells.",2018-10-11,"Westerbeck, J. W.; Machamer, C. E.",,,,True
09ec8daa8e32168d92d05b86de1784c639685fb4,biorxiv,The influenza A virus endoribonuclease PA-X usurps host mRNA processing machinery to limit host gene expression,doi.org/10.1101/442996,,,See https://www.biorxiv.org/about-biorxiv,"Many viruses globally shut off host gene expression to inhibit activation of cell-intrinsic antiviral responses. However, host shutoff is not indiscriminate, since viral proteins and host proteins required for viral replication are still synthesized during shutoff. The molecular determinants of target selectivity in host shutoff remain incompletely understood. Here, we report that the influenza A virus shutoff factor PA-X usurps RNA splicing to selectively target host RNAs for destruction. PA-X preferentially degrades spliced mRNAs, both transcriptome-wide and in reporter assays. Moreover, proximity-labeling proteomics revealed that PA-X interacts with cellular proteins involved in RNA splicing. The interaction with splicing contributes to target discrimination and is unique among viral host shutoff nucleases. This novel mechanism sheds light on the specificity of viral control of host gene expression and may provide opportunities for development of new host-targeted antivirals.",2018-10-14,"Gaucherand, L.; Porter, B. K.; Schmaling, S. K.; Rycroft, C. H.; Kevorkian, Y.; McCormick, C.; Khaperskyy, D. A.; Gaglia, M.",,,,True
564f8823050b52b5f5c36638ac1ae07557963f36,biorxiv,Characterisation of the faecal virome of captive and wild Tasmanian devils using virus-like particles metagenomics and meta-transcriptomics,doi.org/10.1101/443457,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundThe Tasmanian devil is an endangered carnivorous marsupial threatened by devil facial tumour disease (DFTD). While research on DFTD has been extensive, little is known about the viruses present in devils, and whether any of these are of potential conservation relevance for this endangered species.\n\nMethodsUsing both metagenomics based on virus-like particle (VLP) enrichment and sequence-independent amplification (VLP metagenomics), and meta-transcriptomics based on bulk RNA sequencing, we characterised and compared the faecal viromes of captive and wild Tasmanian devils.\n\nResultsA total of 54 devil faecal samples collected from captive (n = 2) and wild (n = 4) populations were processed for virome characterisation using both approaches. We detected many novel, highly divergent viruses, including vertebrate viruses, bacteriophage and other dietary associated plant and insect viruses. In total, 18 new vertebrate viruses, including novel sapelovirus, astroviruses, bocaviruses, papillomaviruses and gammaherpesvirus were identified, as well as known mammalian pathogens including rabbit haemorrhagic disease virus 2 (RHDV2). Captive devils showed significantly lower levels of viral diversity than wild devils. Comparison of the two methodological approaches revealed substantial differences in the number and types of viruses detected, with meta-transcriptomics mainly identifying RNA viruses, and VLP metagenomics largely identifying DNA viruses.\n\nConclusionThis study has greatly expanded our knowledge of eukaryotic viruses in the Tasmanian devil and provides important baseline information that will contribute to the conservation and captive management of this endangered species. In addition, our results showed that a combination of VLP metagenomics and meta-transcriptomics may be a more comprehensive approach to virome characterisation than either method alone.",2018-10-15,"Chong, R.; Shi, M.; Grueber, C. E.; Holmes, E. C.; Hogg, C.; Belov, K.; Barrs, V. R.",,,,True
5a425d474d13cbcfc448f36de539d4a679f7b618,biorxiv,MxB restricts HIV-1 by targeting the tri-hexamer interface of the viral capsid,doi.org/10.1101/444067,,,See https://www.biorxiv.org/about-biorxiv,"Myxovirus resistance protein B (MxB) is an interferon-inducible restriction factor of HIV-1 that blocks nuclear import of the viral genome. Evidence suggests that MxB recognizes higher-order interfaces of the HIV capsid lattice, but the mechanistic details of this interaction are not known. Previous studies have mapped the restriction activity of MxB to its N-terminus encompassing a triple arginine motif 11RRR13. Here we demonstrate a direct and specific interaction between the MxB N-terminus and helical assemblies of HIV-1 capsid protein (CA) using highly purified recombinant proteins. We performed thorough mutagenesis to establish the detailed molecular requirements for the CA interaction with MxB. The results map MxB binding to the interface of three CA hexamers, specifically interactions between positively charged MxB N-terminal residues and negatively charged CA residues. Our crystal structures show that the CA mutations affecting MxB interaction and restriction do not alter the conformation of capsid assembly. In addition, 30 microsecond long all-atom molecular dynamics (MD) simulations of the complex between the MxB N-terminus and the HIV CA tri-hexamer interface show persistent MxB binding and identify a MxB-binding pocket surrounded by three CA hexamers. These results establish the molecular details of the binding of a lattice-sensing host factor onto HIV capsid, and provide insight into how MxB recognizes HIV capsid for the restriction of HIV-1 infection.\n\nAuthor summaryThe human antiviral protein MxB is a restriction factor that fights HIV infection. Previous experiments have demonstrated that MxB targets the HIV capsid, a protein shell that protects the viral genome. To make the conical shaped capsid, HIV CA proteins are organized into a lattice composed of hexamer and pentamer building blocks, providing many interfaces for host proteins to recognize. Through extensive biochemical and biophysical studies and molecular dynamics simulations, we show that MxB is targeting the HIV capsid by recognizing the region created at the intersection of three CA hexamers. We are further able to map this interaction to a few CA residues, located in a negatively-charged well at the interface between the three CA hexamers. This work provides detailed residue-level mapping of the targeted capsid interface and how MxB interacts. This information could inspire the development of capsid-targeting therapies for HIV.",2018-10-15,"Smaga, S. S.; Xu, C.; Summers, B. J.; Digianantonio, K. M.; Perilla, J. R.; Xiong, Y.",,,,True
e7ff9455c483c237c3ee08b9d230b7be65c064bf,biorxiv,Imaging Striatal Dopamine Release Using a Non-Genetically Encoded Near-Infrared Fluorescent Catecholamine Nanosensor,doi.org/10.1101/356543,,,See https://www.biorxiv.org/about-biorxiv,"Neuromodulation plays a critical role in brain function in both health and disease. New optical tools, and their validation in biological tissues, are needed that can image neuromodulation with high spatial and temporal resolution, which will add an important new dimension of information to neuroscience research. Here, we demonstrate the use of a catecholamine nanosensor with fluorescent emission in the 1000-1300 nm near-infrared window to measure dopamine transmission in ex vivo brain slices. These near-infrared catecholamine nanosensors (nIRCats) represent a broader class of nanosensors that can be synthesized from non-covalent conjugation of single wall carbon nanotubes (SWNT) with single strand oligonucleotides. We show that nIRCats can be used to detect catecholamine efflux in brain tissue driven by both electrical stimulation or optogenetic stimulation. Spatial analysis of electrically-evoked signals revealed dynamic regions of interest approximately 2 microns in size in which transients scaled with simulation intensity. Optogenetic stimulation of dopaminergic terminals produced similar transients, whereas optogenetic stimulation of glutamatergic terminals showed no effect on nIRCat signal. Bath application of nomifensine prolonged nIRCat fluorescence signal, consistent with reuptake blockade of dopamine. We further show that the chemically synthetic molecular recognition elements of nIRCats permit measurement of dopamine dynamics in the presence of dopamine receptor agonists and antagonists. These nIRCat nanosensors may be advantageous for future use because i) they do not require virus delivery, gene delivery, or protein expression, ii) their near-infrared fluorescence facilitates imaging in optically scattering brain tissue and is compatible for use in conjunction with other optical neuroscience tool sets, iii) the broad availability of unique near-infrared colors have the potential for simultaneous detection of multiple neurochemical signals, and iv) they are compatible with pharmacology. Together, these data suggest nIRCats and other nanosensors of this class can serve as versatile new optical tools to report dynamics of extracellular neuromodulation in the brain.",2018-10-19,"Beyene, A. G.; Delevich, K.; Del Bonis ODonnell, J. T.; Piekarski, D. J.; Lin, W. C.; Thomas, A. W.; Yang, S. J.; Kosillo, P.; Yang, D.; Wilbrecht, L.; Landry, M. P.",,,,True
a6e5c7919fa1f35244c27ef7e31f6b5817211b66,biorxiv,Origins and Evolution of the Global RNA Virome,doi.org/10.1101/451740,,,See https://www.biorxiv.org/about-biorxiv,"Viruses with RNA genomes dominate the eukaryotic virome, reaching enormous diversity in animals and plants. The recent advances of metaviromics prompted us to perform a detailed phylogenomic reconstruction of the evolution of the dramatically expanded global RNA virome. The only universal gene among RNA viruses is the RNA-dependent RNA polymerase (RdRp). We developed an iterative computational procedure that alternates the RdRp phylogenetic tree construction with refinement of the underlying multiple sequence alignments. The resulting tree encompasses 4,617 RNA virus RdRps and consists of 5 major branches, 2 of which include positive-sense RNA viruses, 1 is a mix of positive-sense (+) RNA and double-stranded (ds) RNA viruses, and 2 consist of dsRNA and negative-sense (-) RNA viruses, respectively. This tree topology implies that dsRNA viruses evolved from +RNA viruses on at least two independent occasions, whereas -RNA viruses evolved from dsRNA viruses. Reconstruction of RNA virus evolution using the RdRp tree as the scaffold suggests that the last common ancestors of the major branches of +RNA viruses encoded only the RdRp and a single jelly-roll capsid protein. Subsequent evolution involved independent capture of additional genes, particularly, those encoding distinct RNA helicases, enabling replication of larger RNA genomes and facilitating virus genome expression and virus-host interactions. Phylogenomic analysis reveals extensive gene module exchange among diverse viruses and horizontal virus transfer between distantly related hosts. Although the network of evolutionary relationships within the RNA virome is bound to further expand, the present results call for a thorough reevaluation of the RNA virus taxonomy.\n\nIMPORTANCEThe majority of the diverse viruses infecting eukaryotes have RNA genomes, including numerous human, animal, and plant pathogens. Recent advances of metagenomics have led to the discovery of many new groups of RNA viruses in a wide range of hosts. These findings enable a far more complete reconstruction of the evolution of RNA viruses than what was attainable previously. This reconstruction reveals the relationships between different Baltimore Classes of viruses and indicates extensive transfer of viruses between distantly related hosts, such as plants and animals. These results call for a major revision of the existing taxonomy of RNA viruses.",2018-10-24,"Dolja, V. V.; Wolf, Y. I.; Kazlauskas, D.; Iranzo, J.; Lucia-Sanz, A.; Kuhn, J. H.; Krupovic, M.; Koonin, E. V.",,,,True
2e7c17caecfe67b64f9b59df404f0761df96987f,biorxiv,National and Regional Influenza-Like-Illness Forecasts for the USA,doi.org/10.1101/309021,,,See https://www.biorxiv.org/about-biorxiv,"Health planners use forecasts of key metrics associated with influenza-like-illness (ILI); near-term weekly incidence, week of season onset, week of peak, and intensity of peak. Here, we describe our participation in a weekly prospective ILI forecasting challenge for the United States for the 2016-17 season and subsequent evaluation of our performance. We implemented a metapopulation model framework with 32 model variants. Variants differed from each other in their assumptions about: the force-of-infection (FOI); use of uninformative priors; the use of discounted historical data for not-yet-observed time points; and the treatment of regions as either independent or coupled. Individual model variants were chosen subjectively as the basis for our weekly forecasts; however, a subset of coupled models were only available part way through the season. Most frequently, during the 2016-17 season, we chose; FOI variants with both school vacations and humidity terms; uninformative priors; the inclusion of discounted historical data for not-yet-observed time points; and coupled regions (when available). Our near-term weekly forecasts substantially over-estimated incidence early in the season when coupled models were not available. However, our forecast accuracy improved in absolute terms and relative to other teams once coupled solutions were available. In retrospective analysis, we found that the 2016-17 season was not typical: on average, coupled models performed better when fit without historically augmented data. Also, we tested a simple ensemble model for the 2016-17 season and found that it underperformed our subjective choice for all forecast targets. In this study, we were able to improve accuracy during a prospective forecasting exercise by coupling dynamics between regions. Although reduction of forecast subjectivity should be a long-term goal, some degree of human intervention is likely to improve forecast accuracy in the medium-term in parallel with the systematic consideration of more sophisticated ensemble approaches.\n\nAuthor summaryIt is estimated that there are between 3 and 5 million worldwide annual seasonal cases of severe influenza illness, and between 290 000 and 650 000 respiratory deaths [1]. Influenza-like-illness (ILI) describes a set of symptoms and is a practical way for health-care workers to easily estimate likely influenza cases. The Centers for Disease Control (CDC) collects and disseminates ILI information, and has, for the last several years, run a forecasting challenge (the CDC Flu Challenge) for modelers to predict near-term weekly incidence, week of season onset, week of peak, and intensity of peak. We have developed a modeling framework that accounts for a range of mechanisms thought to be important for influenza transmission, such as climatic conditions, school vacations, and coupling between different regions. In this study we describe our forecast procedure for the 2016-17 season and highlight which features of our models resulted in better or worse forecasts. Most notably, we found that when the dynamics of different regions are coupled together, the forecast accuracy improves. We also found that the most accurate forecasts required some level of forecaster interaction, that is, the procedure could not be completely automated without a reduction in accuracy.",2018-10-25,"Ben-Nun, M.; Riley, P.; Turtle, J.; Bacon, D.; Riley, S.",,,,True
91233a0c35364955d1fdbf2f980f7220f9bafc70,biorxiv,"A novel real-time PCR assay panel for detection of common respiratory pathogens in a convenient, strip-tube array format",doi.org/10.1101/455568,,,See https://www.biorxiv.org/about-biorxiv,"Commercial multiplex assays, built on different chemistries and platforms are widely available for simultaneous detection of pathogens that cause respiratory infections. However, these tests are often difficult to implement in a resource limited setting because of high cost. In this study, we developed and validated a method for simultaneous testing of common respiratory pathogens (Respanel) by real-time PCR in a convenient, strip-tube array format. Primers and probes for sixteen PCR assays were selected from the literature or newly designed. Following optimization of individual PCR assays, strip-tube arrays were prepared by dispensing primer-probe mixes (PPM) into two sets of 8-tube strips. Nucleic acid extracts from specimens were mixed with PCR master mix, and dispensed column-wise into 2X8-wells of a 96-well plate. PPMs from strip-tubes were then added to the wells using a multichannel pipette for real-time PCR. Individual PCR assays were optimized using previously known specimens (n=397) with 91%-100% concordance with culture, DFA or PCR results. Respanel was then tested in a routine manner at two different sites using specimens (n=147) previously tested by Qiagen Resplex I&II or Fast-Track Diagnostics Respiratory Pathogens 21 assays. The sensitivity, specificity and accuracy of Respanel were 94%, 95% and 95%, respectively, against Resplex and 88%, 100% and 99%, respectively, against FTDRP21. Respanel detected 48% more pathogens (p<0.05) than Resplex but the rate of pathogen detection was not significantly different from FTDRP21. Respanel is a convenient and inexpensive assay that is more sensitive than Resplex and comparable to FTDRP21 for the detection of common respiratory pathogens.",2018-10-29,"Hasan, M. R.; Al Mana, H.; Young, V.; Tang, P.; Thomas, E.; Tan, R.; Tilley, P.",,,,True
12920263b2846c61d6f2b6105189367a8ff1bc39,biorxiv,A diallel of the mouse Collaborative Cross founders reveals strong strain-specific maternal effects on litter size,doi.org/10.1101/458877,,,See https://www.biorxiv.org/about-biorxiv,"Reproductive success in the eight founder strains of the Collaborative Cross (CC) was measured using a diallel-mating scheme. Over a 48-month period we generated 4,448 litters, and 24,782 weaned pups were used across 16 different published experiments. We identified factors that affect the average litter size in a cross by estimating the overall contribution of parent-of-origin, heterosis, inbred, and epistatic effects using a Bayesian zero-truncated overdispersed Poisson mixed model. The phenotypic variance of litter size has a substantial contribution (79%) from unexplained and environmental sources, but no detectable effect of seasonality. Most of the explained variance was due to additive effects (9.2%) and parental sex (maternal vs paternal strain; 5.8%), with epistasis accounting for 3.4%. Within the parental effects, the effect of the dams strain explained more than the sires strain (13.2% vs. 1.8%), and the dams strain effects account for 74.2% of total variation explained. Dams from strains C57BL/6J and NOD/ShiLtJ increased the expected litter size by a mean of 1.66 and 1.79 pups, whereas dams from strains WSB/EiJ, PWK/PhJ, and CAST/EiJ reduced expected litter size by a mean of 1.51, 0.81, and 0.90 pups. Finally, there was no strong evidence for strain-specific effects on sex ratio distortion. Overall, these results demonstrate that strains vary substantially in their reproductive ability depending on their genetic background and that litter size is largely determined by dam.strain rather than sire.strain effects, as expected. This analysis adds to our understanding of factors that influence litter size in mammals, and also helps to explain breeding successes and failures in the extinct lines and surviving CC strains.",2018-10-31,"Shorter, J. R.; Maurizio, P. L.; Bell, T. A.; Shaw, G. D.; Miller, D. R.; Gooch, T. J.; Spence, J. S.; McMillan, L.; Valdar, W.; Pardo-Manuel de Villena, F.",,,,True
7cdd50888f639629380fa9906d73f97010158127,biorxiv,"TIM-1 SERVES AS A NONREDUNDANT RECEPTOR FOR EBOLA VIRUS, ENHANCING VIREMIA AND PATHOGENESIS",doi.org/10.1101/466102,,,See https://www.biorxiv.org/about-biorxiv,"Background.T cell immunoglobulin mucin domain-1 (TIM-1) is a phosphatidylserine (PS) receptor, mediating filovirus entry into cells through interactions with PS on virions. TIM-1 expression has been implicated in Ebola virus (EBOV) pathogenesis; however, it remains unclear whether this is due to TIM-1 serving as a filovirus receptor in vivo or, as others have suggested, TIM-1 induces a cytokine storm elicited by T cell/virion interactions. Here, we use a BSL2 model virus that expresses EBOV glycoprotein and demonstrate the importance of TIM-1 as a virus receptor late during in vivo infection.\n\nMethodology/Principal findings.We used an infectious, recombinant vesicular stomatitis virus expressing EBOV glycoprotein (EBOV GP/rVSV) to assess the role of TIM-1 during in vivo infection. TIM-1-sufficient or TIM-1-deficient BALB/c interferon /{beta} receptor-/- mice were challenged with EBOV GP/rVSV-GFP or G/rVSV-GFP. While G/rVSV caused profound morbidity and mortality in both mouse strains, TIM-1-deficient mice had significantly better survival than TIM-1-expressing mice following EBOV GP/rVSV challenge. EBOV GP/rVSV load in spleen was high and unaffected by expression of TIM-1. However, infectious virus in serum, liver, kidney and adrenal gland was reduced late in infection in the TIM-1-deficient mice, suggesting that virus entry via this receptor contributes to virus load. Consistent with higher virus loads, proinflammatory chemokines trended higher in organs from infected TIM-1-sufficient mice compared to the TIM-1-deficient mice, but proinflammatory cytokines were more modestly affected. To assess the role of T cells in EBOV GP/rVSV pathogenesis, T cells were depleted in TIM-1-sufficient and -deficient mice and the mice were challenged with virus. Depletion of T cells did not alter the pathogenic consequences of virus infection.\n\nConclusions.Our studies provide evidence that at late times during EBOV GP/rVSV infection, TIM-1 increased virus load and associated mortality, consistent with an important role of this receptor in virus entry. This work suggests that inhibitors which block TIM-1/virus interaction may serve as effective antivirals, reducing virus load at late times during EBOV infection.\n\nAuthor summaryT cell immunoglobulin mucin domain-1 (TIM-1) is one of a number of phosphatidylserine (PS) receptors that mediate clearance of apoptotic bodies by binding PS on the surface of dead or dying cells. Enveloped viruses mimic apoptotic bodies by exposing PS on the outer leaflet of the viral membrane. While TIM-1 has been shown to serve as an adherence factor/receptor for filoviruses in tissue culture, limited studies have investigated the role of TIM-1 as a receptor in vivo. Here, we sought to determine if TIM-1 was critical for Ebola virus glycoprotein-mediated infection using a BSL2 model virus. We demonstrate that loss of TIM-1 expression results in decreased virus load late during infection and significantly reduced virus-elicited mortality. These findings provide evidence that TIM-1 serves as an important receptor for Ebola virus in vivo. Blocking TIM-1/EBOV interactions may be effective antiviral strategy to reduce viral load and pathogenicity at late times of EBOV infection.",2018-11-08,"Brunton, B.; Rogers, K.; Phillips, E. K.; Brouillette, R. B.; Bouls, R.; Butler, N. S.; Maury, W.",,,,True
94df380f8a3bab7e30d39cc9d7e95d1f302f5f9f,biorxiv,"A proof of concept for a syndromic surveillance system based on routine ambulance records in the South-West of England, for the influenza season 2016/17.",doi.org/10.1101/462341,,,See https://www.biorxiv.org/about-biorxiv,"The introduction of electronic patient records in the ambulance service provides new opportunities to monitor the population. Most patients presenting to British ambulance services are discharged at scene. Ambulance records are therefore an ideal data source for syndromic early event detection systems to monitor infectious disease in the prehospital population. It has been previously found that tympanic temperature records can be used to detect influenza outbreaks in emergency departments. This study investigated whether routine tympanic temperature readings collected by ambulance crews can be used to detect seasonal influenza. Here we show that these temperature readings do allow the detection of seasonal influenza before methods applied to conventional data sources. The counts of pyretic patients were used to calculate a sliding case ratio (CR) as a measurement to detect seasonal influenza outbreaks. This method does not rely on conventional thresholds and can be adapted to the data. The data collected correlated with seasonal influenza. The 2016/17 outbreak was detected with high specificity and sensitivity, up to 9 weeks before other surveillance programs. An unanticipated outbreak of E. coli was detected in the same dataset. Our results show that ambulance records can be a useful data source for biosurveillance systems. Two outbreaks caused by different infectious agents have been successfully detected. The routine ambulance records allowed to use tympanic temperature readings that can be used as surveillance tool for febrile diseases. Therefore, this method is a valuable addition to the current surveillance tools.",2018-11-09,"Reich, T.; Budka, M.",,,,True
4b57ff228e46255a0ba7114af86ff26af4152d9b,biorxiv,Alterations in sialic-acid O-acetylation glycoforms during murine erythrocyte development,doi.org/10.1101/469254,,,See https://www.biorxiv.org/about-biorxiv,"9-O-acetylation of sialic acid is a common modification that plays important roles in host-pathogen interactions. CASD1 has been described as a sialate-O-acetyltransferase and has been shown to be essential for 9-O-acetylation of sialic acid in some cell lines in vitro. In this study, we used knockout mice to confirm that CASD1 is indeed responsible for 9-O-acetylation of sialic acids in vivo. We observed a complete loss of 9-O-acetylation of sialic acids on the surface of myeloid, erythroid and CD4+ T cells in Casd1-deficient mice. Although 9-O-acetylation of sialic acids on multiple hematopoietic lineages was lost, there were no obvious defects in hematopoiesis. Interestingly, red blood cells from Casd1-deficient mice also lost reactivity to TER-119, a rat monoclonal antibody that is widely used to mark the murine erythroid lineage. The sialic acid glyco-epitope recognized by TER-119 on red blood cells was sensitive to the sialic acid O-acetyl esterase activity of the hemagglutinin esterase from bovine coronavirus but not to the corresponding enzyme from the influenza C virus. During erythrocyte development TER-119+ Ery-A and Ery-B cells could be stained by catalytically inactive bovine coronavirus hemaggutinin-esterase but not by the inactive influenza C hemagglutinin esterase, while TER-119+ Ery-C stage cells and mature erythrocytes were recognized by both virolectins. These results suggest that throughout murine erythrocyte development, cells of the erythroid lineage express a glycoconjugate bearing a modified 7,9-di-O-acetyl form of sialic acid, that is recognized specifically by the bovine coronavirus lectin and not by the influenza C hemagglutinin, and this modified sialic acid moiety is a component of the TER-119 epitope. As erythrocytes mature, the surface of Ery-C cells and mature erythrocytes also acquires a distinct CASD1-dependent 9-O-acetyl sialic acid moiety that can be recognized by virolectins from both influenza C and bovine coronavirus that are specific for 9-O-acetyl sialic acid.",2018-11-14,"Mahajan, V.; Alsufyani, F.; Mattoo, H.; Rosenberg, I.; Pillai, S.",,,,True
bc65a0655d7b88cade3fbec16f3e9706c4cfc5aa,biorxiv,Extensive programmed ribosomal frameshifting in human as revealed by a massively parallel reporter assay,doi.org/10.1101/469692,,,See https://www.biorxiv.org/about-biorxiv,"Programmed ribosomal frameshifting is the controlled slippage of the translating ribosome to an alternative frame. This tightly regulated process is widely employed by human viruses such as HIV and SARS-CoV and is critical for their life cycle and virulence. It is also utilized throughout the tree of life to implement a feedback control mechanism to regulate polyamine levels. However, despite its universality and clinical relevance, a limited number of studies investigated this process on only a few selected examples, largely due to a lack of experimental means. Here, we developed a high-throughput, fluorescence-based approach to assay the frameshifting potential of a sequence. We designed and tested >12.000 sequences based on 15 viral and human frameshifting events, allowing us to elucidate the rules governing ribosomal frameshifting in a systematic way and to discover novel regulatory features. We also utilized our approach to search for novel frameshifting events and identified dozens of previously unknown frameshifting sites in human, showing that programmed ribosomal frameshifting is more common than previously anticipated. We assessed the natural variation in HIV gag-pol frameshifting rates by testing >500 clinical isolates and identified subtype-specific differences as well as associations between viral load in patients and the optimality of gagpol frameshifting rates. We further devised a machine learning algorithm that accurately predicts frameshifting rates of novel variants (up to r=0.70), including subtle differences between HIV isolates (r=0.44), providing a basis for the development of antiviral agents acting on programmed ribosomal frameshifting.",2018-11-14,"Mikl, M.; Alon, A.; Mordret, E.; Pilpel, Y.; Segal, E.",,,,True
6b039b72ca7301c604c743ce7ca3e2c4f5659068,biorxiv,Transgenic mice expressing tunable levels of DUX4 develop characteristic facioscapulohumeral muscular dystrophy-like pathophysiology ranging in severity,doi.org/10.1101/471094,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundAll types of facioscapulohumeral muscular dystrophy (FSHD) are caused by the aberrant myogenic activation of the somatically silent DUX4 gene, which initiates a cascade of cellular events ultimately leading to FSHD pathophysiology. Therefore, FSHD is a dominant gain-of-function disease that is amenable to modeling by DUX4 overexpression. However, there is large variability in the patient population. Typically, progressive skeletal muscle weakness becomes noticeable in the second or third decade of life, yet there are many genetically FSHD individuals who develop symptoms much later in life or remain relatively asymptomatic throughout their lives. Conversely, in rare cases, FSHD may present clinically prior to 5-10 yrs of age, ultimately manifesting as a very severe early onset form of the disease. Thus, there is a need to control the timing and severity of pathology in FSHD-like models.\n\nMethodsWe have recently described a line of conditional DUX4 transgenic mice, FLExDUX4, that develop a myopathy upon induction of human DUX4-fl expression in skeletal muscle. Here, we use the FLExDUX4 mouse crossed with the skeletal muscle-specific and tamoxifen inducible line ACTAl-MerCreMer to generate a highly versatile bi-transgenic mouse model with chronic, low-level DUX4-fl expression and mild pathology, that can be induced to develop more severe FSHD-like pathology in a dose-dependent response to tamoxifen. We identified conditions to reproducibly generate models exhibiting mild, moderate, or severe DUX4-dependent pathophysiology, and characterized their progression.\n\nResultsWe assayed DUX4-fl mRNA and protein levels, fitness, strength, global gene expression, histopathology, and immune response, all of which are consistent with an FSHD-like myopathic phenotype. Importantly, we identified sex-specific and muscle-specific differences that should be considered when using these models for preclinical studies.\n\nConclusionsThe ACTA1-MCM;FLExDUX4 bi-transgenic mouse model expresses a chronic low level of DUX4-fl and has mild pathology and detectable muscle weakness. The onset and progression of moderate to severe pathology can be controlled via tamoxifen injection to provide consistent and readily screenable phenotypes for assessing therapies targeting DUX4-fl mRNA and protein. Thus, these FSHD-like mouse models can be used to study a range of DUX4-fl expression and pathology dependent upon investigator need, through controlled mosaic expression of DUX4.",2018-11-15,"Jones, T. I.; Chew, G.-L.; Barraza-Flores, P.; Schreier, S.; Ramirez, M.; Wuebbles, R. D.; Burkin, D. J.; Bradley, R. K.; Jones, P. L.",,,,True
9211b1703c76e20afdee8fcb9f7996edadef0e9e,biorxiv,"Awareness of MERS-CoV among Staff Members of Prince Sultan Military Medical City in Riyadh, Saudi Arabia",doi.org/10.1101/474205,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundThe Middle East respiratory syndrome coronavirus (MERS-CoV) developed infections that caused serious epidemics. Special priority of awareness and prompt initiative involvement of health workers (HW) during such intensified health situation necessitated an assessment of their preparedness, appropriate attitudes and protective strategies for better efficiency modes and acceleration during emergency.\n\nMethodsHW of Prince Sultan Military Medical city in Riyadh, Saudi Arabia were reviewed through specifically designed questionnaires to acquire the demanded data. It included clinical and demographic information about the viral diseases, associated signs and symptoms, transmission and protection, and attitudes about the MERS-CoV disease.\n\nResultsThe study was accomplished between August and November, 2017 and 477 participants of the medical city, successfully completed the study questionnaire (Appendix I). Females represented a majority and there was an indirectly proportional decrease with the increasing age. Gradual educational increase levels reflected dominance of the university degree holders. Jobs were dominated by nurses and non-Saudis were a majority whilst, the highly experienced, (>10 years) were a minority. A majority recognized the viral transmission methods, popular information sources of MERS-CoV and associated medical terms. Highest scores were observed in dealing with protective aids and recognizing symptoms of disease. High adherence to hand hygiene protocols and correct washing steps were recorded. Correct and high levels were observed in taking preventive measures and avoiding infection. Participants responded correctly to negative and wrong actions that patients should refrain from. High scores were observed in taking appreciable attitudes towards oneself and towards others.\n\nConclusionsExpatriates were majority and nurses were dominant which, necessitates Saudization of this sector. Ministry of health pamphlets and seminars were of less impact in invigilating HW, hence, more attention and efforts are demanded. HW were quite aware of the basic and emergent health policies during epidemic episodes of MERS-CoV.",2018-11-19,"aman, s.; Aljaber, M. I.; Alwehaibi, A. I.; Aman, F. H.; Algaeed, H. A.; Almasoud, S. M.; Alahmari, M. A.; Al Hussain, O.; Elhag, A.",,,,True
03ea3a614b56409d3f099c9ad764864293132540,biorxiv,Live-cell single RNA imaging reveals bursts of translational frameshifting,doi.org/10.1101/478040,,,See https://www.biorxiv.org/about-biorxiv,"Ribosomal frameshifting during the translation of RNA is implicated in both human disease and viral infection. While previous work has uncovered many mechanistic details about single RNA frameshifting kinetics in vitro, very little is known about how single RNA frameshift in living systems. To confront this problem, we have developed technology to quantify live-cell single RNA translation dynamics in frameshifted open reading frames. Applying this technology to RNA encoding the HIV-1 frameshift sequence reveals a small subset (~8%) of the translating pool robustly frameshift in living cells. Frameshifting RNA are preferentially in multi-RNA \""translation factories,\"" are translated at about the same rate as non-frameshifting RNA (~2 aa/sec), and can continuously frameshift for more than four rounds of translation. Fits to a bursty model of frameshifting constrain frameshifting kinetic rates and demonstrate how ribosomal traffic jams contribute to the persistence of the frameshifting state. These data provide novel insight into retroviral frameshifting and could lead to new strategies to perturb the process in living cells.",2018-11-24,"Lyon, K. R.; Aguilera, L. U.; Morisaki, T.; Munsky, B.; Stasevich, T. J.",,,,True
b801b7f92cff2155d98f0e3404229c67b60e2f9f,biorxiv,Realtime 2-5A kinetics suggests interferons β and {lambda} evade global arrest of translation by RNase L,doi.org/10.1101/476341,,,See https://www.biorxiv.org/about-biorxiv,"Cells of all mammals recognize double-stranded RNA (dsRNA) as a foreign material. In response, they release interferons (IFNs) and activate a ubiquitously expressed pseudokinase/endoribonuclease RNase L. RNase L executes regulated RNA decay and halts global translation. Here we developed a biosensor for 2,5-oligoadenylate (2-5A), the natural activator of RNase L. We found that 2-5A was acutely synthesized by cells in response to dsRNA sensing, which immediately triggered cellular RNA cleavage by RNase L and arrested host protein synthesis. However, translation-arrested cells still transcribed IFN-stimulated genes (ISGs) and secreted IFNs of types I and III (IFN-{beta} and IFN-{lambda}). Our data suggests that IFNs escape from the action of RNase L on translation. We propose that 2-5A/RNase L pathway serves to rapidly and accurately suppress basal protein synthesis, preserving privileged production of defense proteins of the innate immune system.\n\nSignificanceRNase L is a mammalian enzyme that can stop global protein synthesis during interferon response. Cells must balance the need to make interferons (which are proteins) with the risk to lose cell-wide translation due to RNase L. This balance can most simply be achieved if RNase L was activated late in the interferon response. However, we show by engineering a biosensor for the RNase L pathway, that on the contrary, RNase L activation precedes interferon synthesis. Further, translation of interferons evades the action of RNase L. Our data suggest that RNase L facilitates a switch of protein synthesis from homeostasis to specific needs of innate immune signaling.",2018-11-26,"Chitrakar, A.; Rath, S.; Donovan, J.; Demarest, K.; Li, Y.; Rao Sridhar, R.; Weiss, S.; Kotenko, S.; Wingreen, N.; Korennykh, A.",,,,True
907da65e13cde5d7ad71f304967a7ab9dcb5efa1,biorxiv,Serum-dependent and independent regulation of PARP2,doi.org/10.1101/483289,,,See https://www.biorxiv.org/about-biorxiv,"PARP2 belongs to a family of proteins involved in cell differentiation, DNA damage repair, cellular energy expenditure, chromatin modeling and cell differentiation. In addition to these overlapping functions with PARP1, PARP2 participates in spermatogenesis, T-cell maturation, extraembryonic endoderm formation and adipogenesis. The function(s) of PARP2 is far from complete, and the mechanism(s) by which the gene and protein are regulated are unknown. In this study, we found that two different mechanisms are used in vitro to regulate PARP2 levels. In the presence of serum, PARP2 is degraded through the ubiquitin-proteasome pathway, however, when serum is removed, PARP2 is rapidly sequestered into an SDS- and urea-insoluble fraction. This sequestration is relieved by serum in a dose-dependent manner, and again PARP2 is detected by immunoblotting. Furthermore, and despite the presence of a putative serum response element in the PARP2 gene, transcription is not affected by serum deprivation. These observations that PARP2 is tightly regulated by distinct pathways highlights the critical roles PARP2 plays under different physiological conditions.",2018-11-29,"Sun, Q.; Gatie, M. I.; Kelly, G. M.",,,,True
d4dde806ec1cfa2209b422f67ed42bcaf6bd7201,biorxiv,DNA segment of African Swine Fever Virus first detected in hard ticks from sheep and bovine,doi.org/10.1101/485060,,,See https://www.biorxiv.org/about-biorxiv,"In this study, we aimed to detect viruses in hard ticks using the small RNA sequencing based method. A 235-bp DNA segment was detected in Dermacentor nuttalli (hard ticks) and D. silvarum (hard ticks) from sheep and bovine, respectively. The detected 235-bp segment had an identity of 99% to a 235-bp DNA segment of African Swine Fever Virus (ASFV) and contained three single nucleotide mutations (C38T, C76T and A108C). C38T, resulting in an single amino acid mutation G66D, suggests the existence of a new ASFV strain, which is different from all reported ASFV strains in NCBI GenBank database. These results also suggest that ASFV could have a wide range of hosts or vectors, beyond the well known Suidae family and soft ticks. Our findings pave the way toward further studies of ASFV transmission and development of prevention and control measures.",2018-12-03,"Chen, Z.; Xu, X.; Yang, X.; Dou, W.; Jin, X.; Ji, H.; Liu, G.; Luo, J.; Yin, H.; Shan, G.",,,,True
5507325ad63261970f22c625abcfa59f99e24efd,biorxiv,Concerted 2-5A-Mediated mRNA Decay and Transcription Reprogram Protein Synthesis in dsRNA Response,doi.org/10.1101/484675,,,See https://www.biorxiv.org/about-biorxiv,"RNA degradation by RNase L during 2-5A-mediated decay (2-5AMD) is a conserved mammalian stress response to viral and endogenous double-stranded RNA (dsRNA). 2-5AMD onsets rapidly and facilitates a switch of protein synthesis from homeostasis to production of interferons (IFNs). To understand the mechanism of this protein synthesis reprogramming, we examined 2-5AMD in human cells. 2-5AMD triggers polysome collapse characteristic of a translation initiation defect, but translation initiation complexes and ribosomes purified from the translation-arrested cells remain functional. Using spike-in RNA-seq we found that basal messenger RNAs (mRNAs) rapidly decay, while mRNAs encoding IFNs and IFN-stimulated genes evade 2-5AMD and accumulate. The IFN evasion results from the combined effect of better mRNA stability and positive feedback amplification in the IFN response. Therefore, 2-5AMD and transcription act in concert to revamp the cellular mRNA composition. The resulting preferential accumulation of innate immune mRNAs establishes \""prioritized\"" synthesis of defense proteins.",2018-12-04,"Rath, S.; Prangley, E.; Donovan, J.; Demarest, K.; Meir, Y.; Wingreen, N.; Korennykh, A.",,,,True
6ad14ceec74dc9b3d3dc6db7fc319b9dc22dc546,biorxiv,Lessening of porcine epidemic diarrhoea virus susceptibility in piglets after editing of the CMP-N-glycolylneuraminic acid hydroxylase gene with CRISPR/Cas9 to nullify N-glycolylneuraminic acid expression,doi.org/10.1101/488510,,,See https://www.biorxiv.org/about-biorxiv,"Porcine epidemic diarrhoea virus (PEDV) devastates the health of piglets but may not infect piglets whose CMP-N-glycolylneuraminic acid hydroxylase (CMAH) gene mutated (knockouts, KO) by using CRISPR/Cas9 gene editing techniques. This hypothesis was tested by using KO piglets challenged with PEDV. Two single-guide RNAs targeting the CMAH gene and Cas9 mRNA were microinjected into the cytoplasm of newly fertilized eggs; 4 live founders generated and proven to be biallelic KO, lacking detectable N-glycolylneuraminic acid (NGNA). The founders were bred, and homozygous offspring were obtained. Two-day-old (in exps. I and III) and 3-day-old (in exp. II) KO and wild-type (WT) piglets were inoculated with TCID50 1x103 PEDV and then fed 20 mL of infant formula (in exps. I and II) or sows colostrum (in exp. III) every 4 hours. In exp. III, the colostrum was offered 6 times and was then replaced with Ringer/5% glucose solution. At 72 hours post-PEDV inoculation (hpi), the animals were euthanized for necropsy, and their intestines were sampled. In all 3 experiments, the piglets showed apparent outward clinical manifestations suggesting that infection occurred despite the CMAH KO. In exp. I, all 6 WT piglets and only 1 of 6 KO piglets died at 72 hpi. Histopathology and immunofluorescence staining showed that the villus epithelial cells of WT piglets were severely exfoliated, but only moderate exfoliation and enterocyte vacuolization was observed in KO piglets. In exp. II, delayed clinical symptoms appeared, yet the immunofluorescence staining/histopathologic inspection (I/H) scores of the two groups differed little. In exp. III, the animals exhibited clinical and pathological signs after inoculation similar to those in exp. II. These results suggest that porcine CMAH KO with nullified NGNA expression are not immune to PEDV but that this KO may lessen the severity of the infection and delay its occurrence.\n\nAuthor summaryThe infection of villus epithelial cells by PEDV has been suggested to occur via putative sialic acid and aminopeptidase N (APN) receptors. Thus, CMP-N-glycolylneuraminic acid hydroxylase (CMAH) gene-mutated pigs that lack N-glycolylneuraminic acid (NGNA) receptors should exhibit resistance to PEDV infection even when APN, which is also responsible for peptide digestion and amino acid absorption and should not be tackled and remains intact. This hypothesis was tested in the present study by generating animals of this type; however, after PEDV challenge, they still showed clinical manifestations of infection. Although the hypothesis could not be verified by the results of the study, some of the immunological and histopathological evidence obtained suggested that this genetic alteration may lessen the severity of infection and delay its occurrence. The results also suggested that binding to NGNA is not a sufficient and necessary condition for PEDV infection of enterocytes. The null expression of CMAH by gene editing induced insignificant resistance to PEDV infection in neonatal piglets.",2018-12-05,"Tu, C.-F.; Chuang, C.-k.; Hsiao, K.-H.; Chen, C.-H.; Chen, C.-M.; Peng, S.-H.; Su, Y.-H.; Chiou, M.-T.; Yen, C.-H.; Hung, S.-W.; Yang, T.-S.; Chen, C.-M.; Ching-Fu Tu, Chin-kai Chuang, Kai-Hsuan Hsiao, Chien-Hong Chen, Chie-Min Chen, Su-Hei Peng, Yu.-Hsiu,  ",,,,True
cdfc8be07677f50c91106e5b56379acb0d0eb289,biorxiv,Stress-induced phospho-ubiquitin formation causes parkin degradation,doi.org/10.1101/484857,,,See https://www.biorxiv.org/about-biorxiv,"Mutations in the E3 ubiquitin ligase parkin are the most common known cause of autosomal recessive parkinsonism. Multiple types of stress decrease parkin protein levels, an effect that may be relevant to sporadic Parkinsons disease (PD), but the mechanism(s) involved in this loss remain largely unclear. We sought to elucidate these mechanisms using a PD-relevant stressor, L-DOPA, the precursor to dopamine, which forms reactive oxygen species (ROS) as well as toxic quinones via auto-oxidation. We find that L-DOPA causes parkin loss through both an oxidative stress-independent and an oxidative stress-dependent pathway. Characterization of the latter reveals that it requires both the kinase PINK1 and parkins interaction with phosphorylated ubiquitin (phospho-Ub) and is mediated by proteasomal degradation.\n\nSurprisingly, mitochondrial parkin activity and autoubiquitination as well as mitophagy are not required for such loss. During stress induced by the oxidative stressor hydrogen peroxide or the metabolic uncoupler CCCP, parkin degradation also requires its association with phospho-Ub, indicating that this mechanism is broadly generalizable. As oxidative stress, metabolic dysfunction and phospho-Ub levels are all elevated in PD patients, we suggest that these changes may lead to the loss of parkin expression in PD.",2018-12-05,"Kovalchuke, L.; Mosharov, E. V.; Levy, O. A.; Greene, L. A.",,,,True
ddefea974fdb2730133e762ece41335b3d3cb94d,biorxiv,Global dynamics of a general vector-borne disease model with two transmission routes,doi.org/10.1101/486720,,,See https://www.biorxiv.org/about-biorxiv,"In this paper, we study the dynamics of a vector-borne disease model with two transmission paths: direct transmission through contact and indirect transmission through vector. The direct transmission is considered to be a non-monotone incidence function to describe the psychological effect of some severe diseases among the population when the number of infected hosts is large and/or the disease possesses high case fatality rate. The system has a disease-free equilibrium which is locally asymptomatically stable when the basic reproduction number (R0) is less than unity and may have up to four endemic equilibria. Analytical expression representing the epidemic growth rate is obtained for the system. Sensitivity of the two transmission pathways were compared with respect to the epidemic growth rate. We numerically find that the direct transmission coefficient is more sensitive than the indirect transmission coefficient with respect to R0 and the epidemic growth rate. Local stability of endemic equilibria is studied. Further, the global asymptotic stability of the endemic equilibrium is proved using Li and Muldowney geometric approach. The explicit condition for which the system undergoes backward bifurcation is obtained. The basic model also exhibits the hysteresis phenomenon which implies diseases will persist even when R0 < 1 although the system undergoes a forward bifurcation and this phenomenon is rarely observed in disease models. Consequently, our analysis suggests that the diseases with multiple transmission routes exhibit bi-stable dynamics. However, efficient application of temporary control in bi-stable regions will curb the disease to lower endemicity. In addition, increase in transmission heterogeneity will increase the chance of disease eradication.",2018-12-07,"Nadim, S. S.; Ghosh, I.; Chattopadhyay, J.",,,,True
2fe18190f7b54e589dccf1d3bbfd73e87bfd2ab9,biorxiv,Animal virus ecology and evolution are shaped by the virus host-body infiltration and colonization pattern.,doi.org/10.1101/492603,,,See https://www.biorxiv.org/about-biorxiv,"The current classification of animal viruses primarily relates to the virus molecular world, the genomic architecture and the corresponding host-cell infection cycle. This virus centered perspective does not make allowance for the precept that virus fitness hinges on the virus transmission success. Virus transmission reflects the infection-shedding-transmission dynamics and, with it, the organ system involvement and other, macroscopic dimensions of the host environment. This study examines the transmission ecology of the world main livestock viruses, 36 in total, belonging to eleven different families, and a mix of RNA, DNA and retroviruses. Viruses are virtually ranked in an outer- to inner-body fashion, based on the shifting organ system involvement and associated infection-shedding-transmission dynamics. As a next step, this ranking is disentangled with the aim to contrast two main host ecologies, poultry plus pig production and ruminant plus equine husbandry, as well as to create a distinction among the RNA, DNA and retroviruses, also ranked in an outer- to inner-body fashion. Spearman correlation reveals the matches among these various virus traits, as pertaining to the two host-ecologies, four infection-shedding-transmission related variables, and the three virus genomes. The collective results reveal the outer- to inner-body shifts in the interplay of host environment, virus-host interactions, and nature of the virus. Two opposing virus evolution pathways emerge, respectively for generalist type, outer-body and for specialist type, inner-body viruses. The ecological virus classification here presented is broadly consistent with the current virus classification system and offers the advantage of bringing substance and cohesion to the interrelationships among viruses and virus families.\n\nAuthor SummaryIt remains unknown how exactly viruses fit in the tree of life. Still, there is growing awareness that viruses as biological replicators are subjected to ecological sorting and so require a viable propagation strategy. In the current analysis I depart from the precept that virus fitness hinges on the virus transmission success. I examine the transmission ecologies of the world main livestock viruses, 36 in total, a collection of pathogens well described in terms of the organ system involvement, infection course, the extent of host damage, virus shedding profile, and virus transmission modes. The viruses are on this basis ranked in an outer- to inner-body fashion, virtually. As a next step, this ranking is disentangled with a view to contrast two main host ecologies, poultry plus pig production and ruminant plus equine husbandry, as well as to create a distinction among the RNA, DNA and retrovirus in the study. The matches among these various virus traits serve to establish the outer- to inner-body shifts in the interplay of host environment, virus-host interactions, and nature of the virus. Two opposing virus evolution pathways emerge, respectively for generalist type, outer-body and for specialist, inner-body viruses.",2018-12-10,"Slingenbergh, J.",,,,True
3472bd9fd14feea62d7520f8ad10a999921a9b1a,biorxiv,METAGENOMIC SEQUENCING FOR COMBINED DETECTION OF RNA AND DNA VIRUSES IN RESPIRATORY SAMPLES FROM PAEDIATRIC PATIENTS,doi.org/10.1101/492835,,,See https://www.biorxiv.org/about-biorxiv,"IntroductionViruses are the main cause of respiratory tract infections. Metagenomic next-generation sequencing (mNGS) enables the unbiased detection of all potential pathogens in a clinical sample, including variants and even unknown pathogens. To apply mNGS in viral diagnostics, there is a need for sensitive and simultaneous detection of RNA and DNA viruses. In this study, the performance of an in-house mNGS protocol for routine diagnostics of viral respiratory infections, with single tube DNA and RNA sample-pre-treatment and potential for automated pan-pathogen detection was studied.\n\nMaterials and MethodsThe sequencing protocol and bioinformatics analysis was designed and optimized including the optimal concentration of the spike-in internal controls equine arteritis virus (EAV) and phocine-herpes virus-1 (PhHV-1).The whole genome of PhHV-1 was sequenced and added to the NCBI database. Subsequently, the protocol was retrospectively validated using a selection of 25 respiratory samples with in total 29 positive and 346 negative PCR results, previously sent to the lab for routine diagnostics.\n\nResultsThe results demonstrated that our protocol using Illumina Nextseq 500 sequencing with 10 million reads showed high repeatability. The NCBI RefSeq database as opposed to the NCBI nucleotide database led to enhanced specificity of virus classification. A correlation was established between read counts and PCR cycle threshold value, demonstrating the semi-quantitative nature of viral detection by mNGS. The results as obtained by mNGS appeared condordant with PCR based diagnostics in 25 out of the 29 (86%) respiratory viruses positive by PCR and in 315 of 346 (91%) PCR-negative results. Viral pathogens only detected by mNGS, not present in the routine diagnostic workflow were influenza C, KI polyomavirus, and cytomegalovirus.\n\nConclusionsSensitivity and analytical specificity of this mNGS protocol was comparable with PCR and higher when considering off-PCR target viral pathogens. All potential viral pathogens were detected in one single test, while it simultaneously obtained detailed information on detected viruses.",2018-12-10,"van Boheemen, S.; van Rijn-Klink, A. L.; Pappas, N.; Carbo, E. C.; Vorderman, R. H. P.; van 't Hof, P. J.; Mei, H.; Claas, E. C. J.; Kroes, A. C. M.; de Vries, J.",,,,False
0da2ec30d7dfdef624833a36890f0297f19d09ec,biorxiv,In trans variant calling reveals enrichment for compound heterozygous variants in genes involved in neuronal development and growth.,doi.org/10.1101/496133,,,See https://www.biorxiv.org/about-biorxiv,"Compound heterozygotes occur when different mutations at the same locus on both maternal and paternal chromosomes produce a recessive trait. Here we present the tool VarCount for the quantification of mutations at the individual level. We used VarCount to characterize compound heterozygous coding variants in patients with epileptic encephalopathy and in the 1000 genomes participants. The Epi4k data contains variants identified by whole exome sequencing in patients with either Lennox-Gastaut Syndrome (LGS) or Infantile Spasms (IS), as well as their parents. We queried the Epi4k dataset (264 trios) and the phased 1000 genomes data (2504 participants) for recessive variants. To assess enrichment, transcript counts were compared between the Epi4k and 1000 genomes participants using minor allele frequency (MAF) cutoffs of 0.5% and 1.0%, and including all ancestries or only probands of European ancestry. In the Epi4k participants, we found enrichment for rare, compound heterozygous mutations in six genes, including three involved in neuronal growth and development - PRTG (p=0.00086, 1% MAF, combined ancestries), TNC (p=0.0221% MAF, combined ancestries), and MACF1 (p=0.0245, 0.5% MAF, EU ancestry). Due the total number of transcripts considered in these analyses, the enrichment detected was not significant after correction for multiple testing and higher powered or prospective studies are necessary to validate the candidacy of these genes. However, PRTG, TNC, and MACF1 are potential novel recessive epilepsy genes and our results highlight that compound heterozygous mutations should be considered in sporadic epilepsy.",2018-12-13,"Cox, A. J.; Grady, F.; Velez, G.; Mahajan, V. B.; Ferguson, P. J.; Kitchen, A.; Darbro, B. W.; Bassuk, A. G.",,,,True
d7c79070914e06addb979161bc85e9a92360ce44,biorxiv,Robust Antibacterial Activity of Tungsten Oxide (WO3-X) Nanodots,doi.org/10.1101/494260,,,See https://www.biorxiv.org/about-biorxiv,"Antibacterial agents are an important tool in the prevention of bacterial infections. Inorganic materials are attractive due to their high stability under a variety of conditions compared to organic antibacterial agents. Herein tungsten oxide nanodots (WO3-X), synthesized by a simple one-pot synthetic approach, was found to exhibit efficient antibacterial capabilities. The analyses with colony-forming units (CFU) showed excellent antibacterial activity of WO3-X against both gram-negative E. coli (Escherichia coli) and gram-positive S. aureus (Staphylococcus aureus) strains. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images revealed clear damage to the bacterial cell membranes, which was further confirmed by molecular dynamics simulations. Additionally, exposure to simulated sunlight was found to further increase germicidal activity of WO3-X nanodots - a 30-minute exposure to sunlight (combining 50 g/mL WO3-X nanodots) showed a 70% decrease in E. coli viability compared to without exposure. Electron spin resonance spectroscopy (ESR) was used to elucidate the underlying mechanism of this photocatalytic activity through the generation of hydroxyl radical species. Cell counting kit-8 (CCK-8) and the live/dead assay were further employed to evaluate the cytotoxicity of WO3-X nanodots on eukaryotic cells, which demonstrated their general biocompatibility. In all, our results suggest WO3-X nanodots have considerable potential in antibacterial applications, while also being biocompatible at large.",2018-12-13,"Duan, G.; Chen, L.; Jing, Z.; De Luna, P.; Wen, L.; Zhang, L.; Zhao, L.; Xu, J.; Li, Z.; Yang, Z.; Zhou, R.",,,,False
08660499ee722a74043f8417faee3e1eeb9d0f5f,biorxiv,International travelers and genomics uncover a ‘hidden’ Zika outbreak,doi.org/10.1101/496901,,,See https://www.biorxiv.org/about-biorxiv,"The ongoing Zika epidemic in the Americas has challenged public health surveillance, response, and control systems. Even as the epidemic appears to be near its end in the Americas, it is unclear whether substantial Zika virus transmission may still be ongoing. This issue is exacerbated by large discrepancies in local case reporting and significant delays in detecting outbreaks due to surveillance gaps. To uncover locations with lingering outbreaks in the Americas, we investigated travel-associated Zika cases diagnosed in the United States and Europe to identify signatures of transmission dynamics that were not captured by local reporting. We found that a large and unreported Zika outbreak occurred in Cuba during 2017, a year after peak transmission in neighboring countries, with cases still appearing in 2018. By sequencing Zika virus from infected travelers, we show that the 2017 outbreak in Cuba was sparked by long-lived lineages of Zika virus introduced from multiple places in the Americas a year prior. Our data suggest that while aggressive mosquito control in Cuba may initially have been effective at mitigating Zika virus transmission, in the absence of vaccines, herd immunity, or strong international coordination, such control measures may need to be maintained to be effective. Our study highlights how Zika virus may still be  silently spreading in the Americas and provides a framework for more accurately understanding outbreak dynamics.",2018-12-14,"Grubaugh, N.; Saraf, S.; Gangavarapu, K.; Watts, A.; Tan, A. L.; Oidtman, R.; Ladner, J. T.; Oliveira, G.; Matteson, N. L.; Kraemer, M. U.; Vogels, C. B.; Hentoff, A.; Bhatia, D.; Stanek, D.; Scott, B.; Landis, V.; Stryker, I.; Cone, M.; Kopp, E.; Cannons, A.; Heberlein-Larson, L.; White, S.; Gillis, L.; Ricciardi, M.; Kwai, J.; Lichtenberger, P.; Magnani, D.; Watkins, D.; Palacios, G.; Hamer, D. H.; GeoSentinel Surveillance Network,  ; Gardner, L.; Perkins, T. A.; Baele, G.; Khan, K.; Morrison, A.; Isern, S.; Michael, S. F.; Andersen, K. G.",,,,True
7808e4cd470a379b12470833f4a6fc7e1b567c96,biorxiv,Homologous Recombination as an Evolutionary Force in African Swine Fever Viruses,doi.org/10.1101/460832,,,See https://www.biorxiv.org/about-biorxiv,"Recent outbreaks of African swine fever virus (ASFV) in China severely influenced the swine industry of the country. Currently, there is no effective vaccine or drugs against ASFVs. How to effectively control the virus is challenging. In this study, we have analyzed all the publicly available ASFV genomes and demonstrated that there was a large genetic diversity of ASFV genomes. Interestingly, the genetic diversity was mainly caused by extensive genomic insertions and/or deletions (indels) instead of the point mutations. The genomic diversity of the virus resulted in proteome diversity. Over 250 types of proteins were inferred from the ASFV genomes, among which only 144 were observed in all analyzed viruses. Further analyses showed that the homologous recombination may contribute much to the indels, as supported by significant associations between the occurrence of extensive recombination events and the indels in the ASFV genomes. Repeated elements of dozens of nucleotides in length were observed to widely distribute and cluster in the adjacent positions of ASFV genomes, which may facilitate the occurrence of homologous recombination. Moreover, two enzymes, which were possibly related to the homologous recombination, i.e., a Lambda-like exonuclease with a YqaJ-like viral recombinase domain, and a DNA topoisomerase II, were found to be conservative in all the analyzed ASFVs. This work highlighted the importance of the homologous recombination in the evolution of the ASFVs, and helped with the strategy development of the prevention and control of the virus.",2018-12-16,"Zhu, Z.; Xiao, C.-T.; Fan, Y.; Cai, Z.; Lu, C.; Zhang, G.; Jiang, T.; Tan, Y.; Peng, Y.",,,,True
e4f66cfdaf836895e7d37941223f11ebc41dbb57,biorxiv,PLANT-Dx: A Molecular Diagnostic for Point of Use Detection of Plant Pathogens,doi.org/10.1101/498998,,,See https://www.biorxiv.org/about-biorxiv,"Synthetic biology based diagnostic technologies have improved upon gold standard diagnostic methodologies by decreasing cost, increasing accuracy, and enhancing portability. However there has been little effort in adapting these technologies towards applications related to point-of-use monitoring of plant and crop health. Here, we take a step towards this vision by developing an approach that couples isothermal amplification of specific plant pathogen genomic sequences with customizable synthetic RNA regulators that are designed to trigger the production of a colorimetric output in cell-free gene expression reactions. We demonstrate our system can sense viral derived sequences with high-sensitivity and specificity, and can be utilized to directly detect viruses from infected plant material. Furthermore, we demonstrate that the entire system can operate using only body heat and naked-eye visual analysis of outputs. We anticipate these strategies to be important components of user-friendly and deployable diagnostic systems that can be configured to detect a range of important plant pathogens.",2018-12-17,"Verosloff, M.; Chappell, J.; Perry, K. L.; Thompson, J. R.; Lucks, J. B.",,,,True
668bff16980e8d6d020f89939588b3eddaa16dbb,biorxiv,Macrophage migration inhibitory factor (MIF) of Syrian golden hamster (Mesocricetus auratus) has similar structure and function as human MIF and promotes pancreatic tumor growth in vivo,doi.org/10.1101/449629,,,See https://www.biorxiv.org/about-biorxiv,"Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that increasingly is being studied in cancers and inflammatory diseases. Though murine models have been instrumental in understanding the functional role of MIF in different pathological conditions, the information obtained from these models is biased towards a specific species. In experimental science, results obtained from multiple clinically relevant animal models always provide convincing data that might recapitulate in humans. Syrian golden hamster (Mesocricetus auratus), is a clinically relevant animal model for multiple human diseases. Hence, the major objectives of this study were to characterize structure and function of hamster MIF, and finally evaluate its effect on pancreatic tumor growth in vivo. Initially, the recombinant hamster MIF (rha-MIF) was cloned, expressed and purified in bacterial expression system. The rha-MIF primary sequence, biochemical properties and crystal structure analysis showed a greater similarity with human MIF. The crystal structure of hamster MIF illustrates that it forms a homotrimer as known in human and mouse. However, hamster MIF exhibits some minor structural variations when compared to human and mouse MIF. The in vitro functional studies show that rha-MIF has tautomerase activity and enhances activation and migration of hamster peripheral blood mononuclear cells (PBMCs). Interestingly, injection of rha-MIF into HapT1 pancreatic tumor bearing hamsters significantly enhanced the tumor growth and tumor associated angiogenesis. Together, the current study shows a structural and functional similarity between hamster and human MIF. Moreover, it has demonstrated that a high-level of circulating MIF originating from non-tumor cells might also promote pancreatic tumor growth in vivo.",2018-12-19,"Dash, P.; Sundaram, R.; Suresh, V.; Sabat, S. C.; Mohapatra, D.; Mohanty, S.; Vasudevan, D.; Senapati, S.",,,,False
26f1c42474966b8daede2912e06175bd8b864f8e,biorxiv,FilmArray Respiratory Panel Integrated in a field Point Of Care dispositive for the diagnosis of respiratory tract infections in rural areas in Senegal,doi.org/10.1101/502575,,,See https://www.biorxiv.org/about-biorxiv,"The development of molecular syndrome-based kits for the diagnosis of respiratory infections offers rapid and sensitive detection of common respiratory pathogens and will have a significant impact on the care of patients. In this study, we present the results obtained after the introduction of the FilmArray respiratory panel in a field Point of care (POC) for the diagnosis of virus and bacteria responsible of respiratory tract infections in Senegal rural area. From February to August 2017, we collected nasal swabs from febrile patients that presented symptoms of respiratory tract infections in three health posts located in Niakhar. Specimens were tested on site by multiplex Polymerase Chain Reaction (PCR), using the FilmArray respiratory panel(R) that targets 20 pathogens, including 17 virus and 3 bacteria (bioMerieux). Nasal swabs were collected from 113 patients. The median age was 4 years (ranging from 4 months to 60 years) and 51 (45%) were males. The prevalence of respiratory pathogens was 37.5% (12/32) during the dry season and 54.3% (44/81) in the rainy season (p=0.16). The prevalence of respiratory pathogen carriage was higher in children under 5 years of age (38/55, 69.1%). The most prevalent micro-organisms detected were influenza B virus (16/113, 14%), human rhinovirus/enterovirus (10/113, 9%), parainfluenzae virus (9/113, 8%), respiratory syncytial virus (8/113, 7%), adenovirus (5/113, 4%), human metapneumovirus (3/113, 3%), Chlamydia pneumoniae (2/113, 2%) and Coronavirus (2/113, 2%). The study has demonstrated that the integration of the FilmArray respiratory panel into a field POC could significantly improve the management of respiratory tract infections in rural areas.\n\nAuthor summaryRespiratory tract infections are one of the leading causes of death worldwide. Populations in underdeveloped countries are the most affected, especially children under 5 years of age. Among the pathogens responsible for these infections, bacteria and viruses are the most identified. In poor countries, laboratory diagnosis can only be done in urban areas. They are generally based on bacteriological, immunological or molecular biology techniques. The concept of POC is not developed in underdeveloped countries. Its existence would have made it possible to carry out RDTs to confirm the clinicians diagnosis and allow rapid management of the patient. In the current situation, the time required to achieve results is often very long for patients. In this study, we sought to demonstrate the significant contribution of the FilmArray respiratory panel in the management of respiratory tract infections in rural areas. We also wanted to reduce the time it takes to deliver results in order to improve patient care. This dispositif was integrated in a field POC which was implemented in Niakhar since 2015, in order to improve the management of emerging diseases. The FilmArray respiratory panel gave us the opportunity to investigate the causes of respiratory tract infections in this area. For each patient, we systematically target 20 pathogens, including 17 viruses and 3 bacteria, with a single multiplex PCR. One of the main results of this study is that children under 5 years of age are the most affected by respiratory tract infections. Then we noted a lack of consultation among adults that could be explained by the banalization of respiratory problems or a preference for traditional care. The fact that children under 5 years of age are the most affected could also serve as a basis for implementing vaccination programmes directly targeting the most vulnerable age groups. It should be noted that for 51% of patients, the result of the diagnosis was negative. It would appear that some pathogens responsible for respiratory tract infections are not targeted by the multiplex PCR. Thus, it would be necessary to screen these pathogens in order to integrate them into a panel that would cover the most pathogens in circulation in this area.",2018-12-22,"Bassene, H.; Edouard, S.; Diatta, G.; Lagier, J. C.; Mediannikov, O.; Fenollar, F.; Diallo, A.; Ba, E. H.; Raoult, D.; Parola, P.; Drancourt, M.; Sokhna, C.",,,,True
acd8d28ae75dc1ec5fea2d767e3158545011c1f7,biorxiv,"The Role of Interleukin-1 cytokine family (IL-1β, IL-37) and interleukin-12 cytokine family (IL-12, IL-35) in eumycetoma infection pathogenesis",doi.org/10.1101/502609,,,See https://www.biorxiv.org/about-biorxiv,"Mycetoma is a neglected tropical disease, endemic in many tropical and subtropical regions, characterised by massive deformity and disability and can be fatal if untreated early and appropriately. Interleukins (IL)-35 and IL-37 are newly discovered cytokines that play an important role in suppressing the immune system. However, the expression of these interleukins in patients with Madurella mycetomatis (M. mycetomatis) induced eumycetoma has not yet been explored. This study aims to determine the levels of the IL-1 family (IL-1{beta}, IL-37) and IL-12 family (IL-12, IL-35) in a group of these patients and the association between these cytokines levels and the patients demographic characteristics. The present, a case-control study was conducted at the Mycetoma Research Centre, Soba University Hospital, University of Khartoum, Sudan and it included 140 individuals. They were divided into two groups; group I: healthy controls [n = 70; median age 25 years (range 12 to 70 years)]. Group II: mycetoma patients [n = 70 patients; median age 25 (range 13 to 70 years)]. Cytokines levels were measured in sera using enzyme-linked immunosorbent assay (ELISA).\n\nThere was no significant correlation between the IL-1{beta} and IL-12 levels and the lesions size and disease duration, whereas levels of IL-37 and IL-35 were significantly correlated with that. The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a significant negative association with IL-1{beta} cytokine, where a unit increment in IL-1{beta} will decrease the levels of IL-37 by 35.28 pg/ml. The levels of IL-37 among the patients with a duration of mycetoma infection [&le;] one year had significantly decreased by an average of 18.45 compared to patients with a mycetoma infections duration of [&ge;] 5years (reference group). Furthermore, the risk factors of higher levels of IL-35 in mycetoma patients revealed a significant negative association with IL-12, as a unit increment in IL-12 decreases the levels of IL-35by 8.99 pg/ml (p < 0.001). Levels of IL-35 among the patients with duration of mycetoma infection [&le;] one year had significantly decreased (p-value = 0.002) on average by 41.82 compared to patients with a duration of mycetoma infection [&ge;] five years (reference group). In conclusion, this study indicates that both IL-35 and IL-37 are negatively associated with the levels of IL-1{beta} and IL-12 in eumycetoma mycetoma infection; and high levels of IL-37 and IL-35 may have a negative impact on disease progression.\n\nAuthors SummaryMycetoma is a progressive chronic granulomatous fungal or bacterial infection that may result in massive destruction of subcutaneous tissues, muscles and bones. Mycetoma is a neglected disease which is endemic in many tropical and subtropical areas. If the disease is not treated properly, eventually it ends up with amputation and adverse medical, health and socioeconomic effects on patients and the community.\n\nPrevious data suggested a crucial role of adaptive immunity in host resistance to causative agents and the disease progression. The recently identified IL-35 and IL-37 cytokines revealed an important role in immune suppression. Nevertheless, the expression of these interleukins in patients with mycetoma has not yet been investigated. Therefore, the present case-control study aimed to determine the levels of IL-1 family (IL-1{beta}, IL-37) and IL-12 family (IL-12, IL-35) in these patients and the association between these cytokines levels and the patients demographic characteristics.\n\nThe results of this study showed that the levels of IL-37 and IL-35 were consistently positively correlated with different diameters of mycetoma lesions as well as its duration. However, the levels of IL-1{beta} and IL-12 were consistently negatively correlated with different diameters of lesions and the duration of mycetoma infection. The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a significant negative association with IL-1{beta} cytokine. Furthermore, the risk factors of higher levels of IL-35 in patients of mycetoma revealed a significant negative association with IL-12. These findings uncover a possible the role of IL-35 and IL-37 in the pathogenesis of mycetoma and may declare their potential value in the treatment of mycetoma.",2018-12-22,"Fahal, A. H.; Abushouk, A.; Nasr, A.; Masuadi, E.; Allam, G.; Siddig, E. E.",,,,True
5ba386b58c8d194e8cbe581eed95f7c64d05cd53,biorxiv,A Toolkit for Rapid Modular Construction of Biological Circuits in Mammalian Cells,doi.org/10.1101/506188,,,See https://www.biorxiv.org/about-biorxiv,"The ability to rapidly assemble and prototype cellular circuits is vital for biological research and its applications in biotechnology and medicine. Current methods that permit the assembly of DNA circuits in mammalian cells are laborious, slow, expensive and mostly not permissive of rapid prototyping of constructs. Here we present the Mammalian ToolKit (MTK), a Golden Gate-based cloning toolkit for fast, reproducible and versatile assembly of large DNA vectors and their implementation in mammalian models. The MTK consists of a curated library of characterized, modular parts that can be easily mixed and matched to combinatorially assemble one transcriptional unit with different characteristics, or a hierarchy of transcriptional units weaved into complex circuits. MTK renders many cell engineering operations facile, as showcased by our ability to use the toolkit to generate single-integration landing pads, to create and deliver libraries of protein variants and sgRNAs, and to iterate through Cas9-based prototype circuits. As a biological proof of concept, we used the MTK to successfully design and rapidly construct in mammalian cells a challenging multicistronic circuit encoding the Ebola virus (EBOV) replication complex. This construct provides a non-infectious biosafety level 2 (BSL2) cellular assay for exploring the transcription and replication steps of the EBOV viral life cycle in its host. Its construction also demonstrates how the MTK can enable important and time sensitive applications such as the rapid testing of pharmacological inhibitors of emerging BSL4 viruses that pose a major threat to human health.",2018-12-26,"Fonseca, J. P.; Bonny, A. R.; Kumar, G. R.; Ng, A. H.; Town, J.; Wu, Q. C.; Aslankoohi, E.; Chen, S. Y.; Harrigan, P.; Osimiri, L. C.; Kistler, A. L.; El-Samad, H.",,,,True
52a8089242fbe484e537cd8ea5c0c9ec3bf32150,biorxiv,C19ORF66 broadly escapes viral-induced endonuclease cleavage and restricts Kaposi Sarcoma Associated Herpesvirus (KSHV),doi.org/10.1101/506410,,,See https://www.biorxiv.org/about-biorxiv,"One striking characteristic of certain herpesviruses is their ability to induce rapid and widespread RNA decay in order to gain access to host resources. This phenotype is induced by viral endoribonucleases, including SOX in KSHV, muSOX in MHV68, BGLF5 in EBV and vhs in HSV-1. Here, we performed comparative RNA-seq upon expression of these herpesviral endonucleases in order to characterize their effect on the host transcriptome. Consistent with previous reports, we found that approximately two thirds of transcripts are downregulated in cells expressing any of these viral endonucleases. Among transcripts spared from degradation, we uncovered a cluster of transcripts that systematically escape degradation from all tested endonucleases. Among these escapees, we identified C19ORF66 and reveal that like the previously identified escapees, this transcript is protected from degradation by its 3UTR. We then show that C19ORF66, a known anti-viral protein, is a potent KSHV restriction factor, suggesting that its ability to escape viral cleavage may be an important component of the host response to viral infection. Collectively, our comparative approach is a powerful tool to pinpoint key regulators of the viral-host interplay and led us to uncover a novel KSHV regulator.",2018-12-26,"Rodriguez, W.; Srivastav, A.; Muller, M.",,,,True
a5944e859b017fd4504ea042daaec613f3fba167,biorxiv,"Human, Nonhuman Primate, and Bat Cells Are Broadly Susceptible to Tibrovirus Particle Cell Entry",doi.org/10.1101/507350,,,See https://www.biorxiv.org/about-biorxiv,"In 2012, the genome of a novel rhabdovirus, Bas-Congo virus, was discovered in the acute-phase serum of a Congolese patient with presumed viral hemorrhagic fever. In the absence of a replicating virus isolate, fulfilling Kochs postulates to determine whether Bas-Congo virus is indeed a human virus and/or pathogen has been impossible. However, experiments with vesiculoviral particles pseudotyped with Bas-Congo glycoprotein suggested that Bas-Congo virus particles can enter cells from multiple animals, including humans. In 2015, genomes of two related viruses, Ekpoma virus 1 and Ekpoma virus 2, were detected in human sera in Nigeria. Isolates could not be obtained. Phylogenetic analyses led to the classification of Bas-Congo virus, Ekpoma virus 1, and Ekpoma virus 2 in the same genus, Tibrovirus, together with five biting midge-borne rhabdoviruses (i.e., Beatrice Hill virus, Bivens Arm virus, Coastal Plains virus, Sweetwater Branch virus, and Tibrogargan virus) not known to infect humans. Using individual recombinant vesiculoviruses expressing the glycoproteins of all eight known tibroviruses and more than 75 cell lines representing different animal species, we demonstrate that the glycoproteins of all tibroviruses can mediate vesiculovirus particle entry into human, bat, nonhuman primate, cotton rat, boa constrictor, and Asian tiger mosquito cells. Using four of five isolated authentic tibroviruses (i.e., Bivens Arm virus, Coastal Plains virus, Sweetwater Branch virus, and Tibrogargan virus), our experiments indicate that many cell types may be partially resistant to tibrovirus replication after virion cell entry. Consequently, experimental data solely obtained from experiments using tibrovirus surrogate systems (e.g., vesiculoviral pseudotypes, recombinant vesiculoviruses) cannot be used to predict whether Bas-Congo virus, or any other tibrovirus, infects humans.",2018-12-27,"Cai, Y.; Yu, S.; Jangra, R.; Postnikova, E.; Wada, J.; Tesh, R.; Whelan, S.; Lauck, M.; Wiley, M.; Finch, C.; Radoshitzky, S.; O'Connor, D.; Palacios, G.; Chandran, K.; Chiu, C.; Kuhn, J.",,,,True
f89618a7949b8ff9b92c87ca5b839a3107957b5c,biorxiv,A novel defective recombinant porcine enterovirus G virus carrying a porcine torovirus papain-like cysteine protease gene and a putative anti-apoptosis gene in place of viral structural protein genes,doi.org/10.1101/510131,,,See https://www.biorxiv.org/about-biorxiv,"Enterovirus G (EV-G) belongs to the family of Picornaviridae. Two types of recombinant porcine EV-Gs carrying papain-like cysteine protease (PLCP) gene of porcine torovirus, a virus in Coronaviridae, are reported. Type 1 recombinant EV-Gs are detected in pig feces in Japan, USA, and Belgium and carry the PLPC gene at the junction site of 2C/3A genes, while PLPC gene replaces the viral structural genes in type 2 recombinant EV-G detected in pig feces in a Chinese farm. We identified a novel type 2 recombinant EV-G carrying the PLCP gene with flanking sequences in place of the viral structural genes in pig feces in Japan. The ~0.3 kb-long upstream flanking sequence had no sequence homology with any proteins deposited in GenBank, while the downstream ~0.9 kb-long flanking sequence included a domain having high amino acid sequence homology with a baculoviral inhibitor of apoptosis repeat superfamily. The pig feces, where the novel type 2 recombinant EV-G was detected, also carried type 1 recombinant EV-G. Although the phylogenetic analysis suggested that these two recombinant EV-Gs have independently evolved, type 1 recombinant EV-G might have served as a helper virus by providing viral structural proteins for dissemination of the type 2 recombinant EV-G.",2019-01-02,"Imai, R.; Nagai, M.; Sakaguchi, S.; Masuda, T.; Kuroda, M.; Oba, M.; Katayama, Y.; Naoi, Y.; Tsuchiaka, S.; Omatsu, T.; Yamazato, H.; Makino, S.; Mizutani, T.",,,,True
a6b05fa393f9404c906099e179ca476294068394,biorxiv,Kinetic Analysis of Bacteriophage Sf6 Binding to Outer Membrane Protein A Using Whole Virions,doi.org/10.1101/509141,,,See https://www.biorxiv.org/about-biorxiv,"For successful infection, viruses must recognize their respective host cells. A common mechanism of host recognition by viruses is to utilize a portion of the host cell as a receptor. Bacteriophage Sf6, which infects Shigella flexneri, uses lipopolysaccharide as a primary receptor and then requires interaction with a secondary receptor, a role that can be fulfilled by either outer membrane proteins (Omp) A or C. Our previous work showed that specific residues in the loops of OmpA mediate Sf6 infection. To better understand Sf6 interactions with OmpA loop variants, we determined the kinetics of these interactions through the use of biolayer interferometry, an optical biosensing technique that yields data similar to surface plasmon resonance. Here, we successfully tethered whole Sf6 virions, determined the binding constant of Sf6 to OmpA to be 36 nM. Additionally, we showed that Sf6 bound to five variant OmpAs and the resulting kinetic parameters varied only slightly. Based on these data, we propose a model in which Sf6: Omp receptor recognition is not solely based on kinetics, but likely also on the ability of an Omp to induce a conformational change that results in productive infection.",2019-01-02,"Hubbs, N. B.; Whisby-Pitts, M. M.; McMurry, J. L.",,,,True
d17e180b386620faf190e2a7893b3fccaa47637e,biorxiv,The respiratory virome and exacerbations in patients with chronic obstructive pulmonary disease,doi.org/10.1101/509919,,,See https://www.biorxiv.org/about-biorxiv,"IntroductionExacerbations are major contributors to morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), and respiratory bacterial and viral infections are an important trigger for the occurrence of such exacerbations. However, using conventional diagnostic techniques, a causative agent is not always found. Metagenomic next-generation sequencing (mNGS) allows analysis of the complete virome, but has not yet been applied in COPD exacerbations.\n\nObjectivesTo study the respiratory virome in nasopharyngeal samples during COPD exacerbations using mNGS.\n\nStudy design88 nasopharyngeal swabs from 63 patients from the Bergen COPD Exacerbation Study (2006-2010) were analysed by mNGS and in-house qPCR for respiratory viruses. Both DNA and RNA were sequenced simultaneously using an lllumina library preparation protocol with in-house adaptations.\n\nResultsBy mNGS, 23/88 samples tested positive. Sensitivity and specificity were both 96% for diagnostic targets (23/24 and 1067/1120, respectively). Viral pathogens only detected by mNGS were herpes simplex virus type 1 and coronavirus OC43. A positive correlation was found between Cq value and mNGS viral species reads (p=0.008). Patients with viral pathogens had lower percentages of bacteriophages (p<0.000). No correlation was found between viral reads (species and genus level) and clinical markers.\n\nConclusionsThe mNGS protocol used was highly sensitive and specific for semi-quantitative detection of respiratory viruses. Excellent negative predictive value implicates the power of mNGS to exclude any infectious cause in one test, with consequences for clinical decision making. Reduced abundance of bacteriophages in COPD patients with viral pathogens implicates skewing of the virome, and speculatively the bacterial population, during infection.",2019-01-02,"van Rijn, A. L.; van Boheemen, S.; Carbo, E. C.; Pappas, N.; Sidorov, I.; Mei, H.; Aanerud, M.; Bakke, P.; Claas, E. C. J.; Eagan, T. M.; Hiemstra, P. S.; Kroes, A. C. M.; de Vries, J. J. C.",,,,False
ea84759e67802b696a5c60503c024546e542d572,biorxiv,Influenza A virus surface proteins are organized to help penetrate host mucus,doi.org/10.1101/512467,,,See https://www.biorxiv.org/about-biorxiv,"Influenza A virus (IAV) enters cells by binding to sialic acid on the cell surface. To accomplish this while avoiding immobilization by sialic acid in host mucus, viruses rely on a balance between the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Although genetic aspects of this balance are well-characterized, little is known about how the spatial organization of these proteins in the viral envelope may contribute. Using site-specific fluorescent labeling and super-resolution microscopy, we show that HA and NA are asymmetrically distributed on the surface of filamentous viruses, creating an organization of binding and cleaving activities that causes viruses to step consistently away from their NA-rich pole. This Brownian ratchet-like diffusion produces persistent directional mobility that resolves the viruss conflicting needs to both penetrate mucus and stably attach to the underlying cells, and could contribute to the prevalence of the filamentous phenotype in clinical isolates of IAV.",2019-01-04,"Vahey, M. D.; Fletcher, D. A.",,,,True
bcef0894cf382a83c2aa4d9c803978780c2809db,biorxiv,The MHC class-II HLA-DR receptor mediates bat influenza A-like H17N10 virus entry into mammalian cells,doi.org/10.1101/507467,,,See https://www.biorxiv.org/about-biorxiv,"Bats are notorious reservoirs of diverse, potentially zoonotic viruses, exemplified by the evolutionarily distinct, influenza A-like viruses H17N10 and H18N11 (BatIVs). The surface glycoproteins [haemagglutinin (H) and neuraminidase (N)] of BatIVs neither bind nor cleave sialic acid receptors, which suggests that these viruses employ cell attachment and entry mechanisms that differ from those of classical influenza A viruses (IAVs). Identifying the cellular factors that mediate entry and determine susceptibility to infection will help assess the host range of BatIVs. Here, we investigated a range of cell lines from different species for their susceptibility to infection by pseudotyped viruses (PV) bearing bat H17 and/or N10 envelope glycoproteins. We show that a number of human haematopoietic cancer cell lines and the canine kidney MDCK II (but not MDCK I) cells are susceptible to H17-pseudotypes (H17-PV). We observed with microarrays and qRT-PCR that the dog leukocyte antigen DLA-DRA mRNA is over expressed in late passaged parental MDCK and commercial MDCK II cells, compared to early passaged parental MDCK and MDCK I cells, respectively. The human orthologue HLA-DRA encodes the alpha subunit of the MHC class II HLA-DR antigen-binding heterodimer. Small interfering RNA- or neutralizing antibody-targeting HLA-DRA, drastically reduced the susceptibility of Raji B cells to H17-PV. Conversely, over expression of HLA-DRA and its paralogue HLA-DRB1 on the surface of the unsusceptible HEK293T/17 cells conferred susceptibility to H17-PV. The identification of HLA-DR as an H17N10 entry mediator will contribute to a better understanding of the tropism of the virus and will elucidate its zoonotic transmission.",2019-01-04,"Giotis, E. S.; Carnell, G.; Young, E. F.; Ghanny, S.; Soteropoulos, P.; Barclay, W. S.; Skinner, M. A.; Temperton, N.",,,,True
691f54c001708f6684ae7837adc749fe09404e61,biorxiv,Contesting the evidence for -1 frameshifting in immune-functioning C-C chemokine receptor 5 (CCR5) - the HIV-1 co-receptor,doi.org/10.1101/513333,,,See https://www.biorxiv.org/about-biorxiv,"During the decoding of a subset of mRNAs a proportion of ribosomes productively shift to the -1 reading frame at a specific, slippage-prone site1. While the great majority of occurrences of the \""Programmed -1 Ribosomal Frameshifting\"" (-1 PRF) involve viruses2, other mobile elements or retroelements1, a dramatic instance of utilized human cellular -1 frameshifting in a non-retroelement derived mRNA has been reported. The mRNA for which -1 frameshifting was claimed due to a stimulatory pseudoknot is that which encodes immune functioning C-C chemokine receptor 5 (CCR5), the HIV-1 co-receptor3. The publication ascribed the importance of the reporter CCR5 mRNA frameshifting directing translating ribosomes to a premature termination codon leading to mRNA destabilization via the nonsense-mediated decay pathway (NMD), rather than creating a C- ...",2019-01-08,"Khan, Y. A.; Loughran, G.; Atkins, J. F.",,,,True
903fae9f919c35de8ea1647788137e160277cc22,biorxiv,The bat influenza H17N10 can be neutralized by broadly-neutralizing monoclonal antibodies and its neuraminidase can facilitate viral egress.,doi.org/10.1101/499947,,,See https://www.biorxiv.org/about-biorxiv,"The diversity of subtypes within the Influenza A virus genus has recently expanded with the identification of H17N10 and H18N11 from bats. In order to further study the tropism and zoonotic potential of these viruses, we have successfully produced lentiviral pseudotypes bearing both haemagglutinin H17 and neuraminidase N10. These pseudotypes were shown to be efficiently neutralized by the broadly-neutralizing monoclonal antibodies CR9114 and FI6. Our studies also confirm previous reports that H17 does not use sialic acid as its cellular receptor, as pseudotypes bearing the H17 envelope glycoprotein are released into the cell supernatant in the absence of NA. However, we demonstrate that N10 facilitates heterosubtypic (H5 and H7) influenza HA-bearing pseudotype release in the absence of another source of NA, significantly increasing luciferase pseudotype production titres. Despite this, N10 shows no activity in the enzyme-linked lectin assay used for traditional sialidases. These findings suggest that this protein plays an important role in viral egress, but is perhaps involved in further accessory roles in the bat influenza lifecycle that are yet to be discovered. Thus we show the lentiviral pseudotype system is a useful research tool, and amenable for investigation of bat influenza tropism, restriction and sero-epidemiology, without the constraints or safety issues with producing a replication-competent virus, to which the human population is naive.\n\nSignificance statementInfluenza virus is responsible for mortality and morbidity across the globe; human populations are constantly at risk of newly emerging strains from the aquatic bird reservoir which harbors most of the subtypes of influenza A (H1-H16). Recently identified subtypes (H17N10, H18N11) from bats have broadened the reservoir from which potential pandemic strains of influenza can emerge. To evaluate the potential for these novel subtypes to cross over into human populations, their ability to establish an infection, in addition to the extent of cross-reactive immunity established by human seasonal strains needs to be investigated. This study highlights a novel platform for the study of the bat H17 and N10 envelope glycoproteins, using a lentiviral pseudotype system. Following the generation of this pseudotype it was employed in cell entry and microneutralization assays. These showed that two well-characterised monoclonal antibodies (mAb) which target avian and human influenza subtypes will also neutralize H17. Furthermore the data presented in this study show a novel aspect of the N10 glycoprotein in its ability to facilitate the budding of pseudotypes bearing different influenza HAs.",2019-01-12,"Carnell, G.; Giotis, E.; Grehan, K.; Ferrara, F.; Mather, S.; Molesti, E.; Scott, S.; Pessi, A.; Lacek, K.; Temperton, N.",,,,False
e226beab8af4202a5182f7603fe468dedd5dee6a,biorxiv,Biological Evaluation of Molecules of the azaBINOL Class as Antiviral Agents: Specific Inhibition of HIV-1 RNase H Activity by 7-Isopropoxy-8-(naphth-1-yl)quinoline,doi.org/10.1101/525105,,,See https://www.biorxiv.org/about-biorxiv,"Inspired by bioactive biaryl-containing natural products found in plants and the marine environment, a series of synthetic compounds belonging to the azaBINOL chiral ligand family was evaluated for antiviral activity against HIV-1. Testing of 39 unique azaBINOLs in a singleround infectivity assay resulted in the identification of three promising antiviral compounds, including 7-isopropoxy-8-(naphth-1-yl)quinoline (azaBINOL B#24), which exhibited low-micromolar activity. The active compounds and several close structural analogues were further tested against three different HIV-1 envelope pseudotyped viruses as well as in a full-virus replication system (EASY-HIT). Mode-of-action studies using a time-of-addition assay indicated that azaBINOL B#24 acts after viral entry but before viral assembly and budding. HIV-1 reverse transcriptase (RT) assays that individually test for polymerase and RNase H activity were used to demonstrate that B#24 inhibits RNase H activity, most likely allosterically. Further binding analysis using bio-layer interferometry (BLI) showed that B#24 interacts with HIV-1 RT in a highly specific manner. These results indicate that azaBINOL B#24 is a potentially viable, novel lead for the development of new HIV-1 RNase H inhibitors. Furthermore, this study demonstrates that the survey of libraries of synthetic compounds, designed purely with the goal of facilitating chemical synthesis in mind, may yield unexpected and selective drug leads for the development of new antiviral agents.",2019-01-23,"Overacker, R. D.; Banerjee, S.; Neuhaus, G. F.; Milicevic Sephton, S.; Herrmann, A.; Strother, J. A.; Brack-Werner, R.; Blakemore, P. R.; Loesgen, S.",,,,True
8eef6fec694446e150e95dfbef3a3579ae8806d3,biorxiv,Hand-hygiene mitigation strategies against globaldisease spreading through the air transportationnetwork,doi.org/10.1101/530618,,,See https://www.biorxiv.org/about-biorxiv,"Hand hygiene is considered as an efficient and cost-effective way to limit the spread of diseases and, as such, it is recommended by both the World Health Organization (WHO) and the Centres for Disease Control and Prevention (CDC). While the effect of hand washing on individual transmissibility of a disease has been studied through medical and public-health research, its potential as a mitigation strategy against a global pandemic has not been fully explored yet. In this study, we investigate contagion dynamics through the world air transportation network and analyze the impact of hand-hygiene behavioural changes of airport population against the spread of infectious diseases worldwide. Using a granular dataset of the world air transportation traffic, we build a detailed individual mobility model that controls for the correlated and recurrent nature of human travel and the waiting-time distributions of individuals at different locations. We perform a Monte-Carlo simulation study to assess the impact of different hand-washing mitigation strategies at the early stages of a global epidemic. From the simulation results we find that increasing the hand cleanliness homogeneously at all airports in the world can inhibit the impact of a potential pandemic by 24 to 69%. By quantifying and ranking the contribution of the different airports to the mitigation of an epidemic outbreak, we identify ten key airports at the core of a cost-optimal deployment of the hand-washing strategy: increasing the engagement rate at those locations alone could potentially reduce a world pandemic by 8 to 37%. This research provides evidence of the effectiveness of hand hygiene in airports on the global spread of infectious diseases, and has important implications for the way public-health policymakers may design new effective strategies to enhance hand hygiene in airports through behavioral changes.",2019-01-26,"Nicolaides, C.; Avraam, D.; Cueto-Felgueroso, L.; Gonzalez, M. C.; Juanes, R.",,,,True
6c3e940e2848827af17dd23005a9dee8ac0cd349,biorxiv,Mechanistic insights into Zika virus NS3 helicase inhibition by Epigallocatechin-3-gallate,doi.org/10.1101/530600,,,See https://www.biorxiv.org/about-biorxiv,"Since 2007, repeated outbreaks of Zika virus (ZIKV) has affected millions of people worldwide and created global health concern with major complications like microcephaly and Guillain Barre syndrome. Generally, ZIKV transmits through mosquitoes (Aedes aegypti) like other flaviviruses, but reports show blood transfusion and sexual mode of ZIKV transmission which further makes the situation alarming. Till date, there is not a single Zika specific licensed drug or vaccine present in the market. However, in recent months, several antiviral molecules have been screened against viral and host proteins. Among those, -Epigallocatechin-3-gallate (EGCG), a green tea polyphenol has shown great virucidal potential against flaviviruses including ZIKV. However, the mechanistic understanding of EGCG targeting viral proteins is not yet entirely deciphered except little is known about its interaction with viral envelope protein and viral protease. Since literature has shown significant inhibitory interactions of EGCG against various kinases and bacterial DNA gyrases; we designed our study to find inhibitory actions of EGCG against ZIKV NS3 helicase. NS3 helicase is playing a significant role in viral replication by unwinding RNA after hydrolyzing NTP. We employed molecular docking and simulation approach and found significant interactions at ATPase site and also at RNA binding site. Further, the enzymatic assay has shown significant inhibition of NTPase activity with an IC50 value of 295.7 nM and Ki of 0.387 (error 0.034) micromolar. Our study suggests the possibility that EGCG could be considered as prime backbone molecule for further broad-spectrum and multitargeted inhibitor development against ZIKV and other flaviviruses.",2019-01-26,"Kumar, D.; Sharma, N.; Aarthy, M.; Singh, S.; Giri, R.",,,,True
fda076d8d8b2fb52990e3db1982e4af2ff0fb08e,biorxiv,Computational vaccinology approach: Designing an efficient multi-epitope peptide vaccine against Cryptococcus neoformans var. grubii heat shock 70KDa protein,doi.org/10.1101/534008,,,See https://www.biorxiv.org/about-biorxiv,"IntroductionCryptococcosis is a ubiquitous opportunistic fungal disease caused by Cryptococcus neoformans var. grubii. It has high global morbidity and mortality among HIV patients and none-HIV carriers with 99% and 95% respectively. Furthermore, the increasing prevalence of undesired toxicity profile of antifungal, multi-drug resistant organism, and the scarcity of FDA authorized vaccines, where the hallmark in the present days. This study was undertaken to design a reliable multi-epitope peptide vaccine against highly conserved immunodominant heat shock 70KDa protein of Cryptococcus neoformans var. grubii that covers a considerable digit of the world population through implementing computational vaccinology approach.  Materials and MethodsA total of 38 Sequences of Cryptococcus neoformans var. grubiis heat shock 70KDa protein were retrieved from NCBI protein database. Different prediction tools were used to analyze the aforementioned protein at Immune Epitope Database (IEDB) to discriminate the most promising T-cell and B-cell epitopes. Then the proposed epitopes were subjected to Population coverage analysis tool to compute global populations coverage. Finally, the projected epitopes were ranked based on their scores and binding modes through using Moe 2007 program.  Outstanding Results and ConclusionOur prime vaccine candidate was a putative ten promising epitopes (ANYVQASEK, NYVQASEK, KSVEKPAS, TPQQPPAQ, YVYDTRGKL, FYRQGAFEL, FTQLVAAYL, FFGGKVLNF, FDYALVQHF, and FINAQLVDV). Together, these epitopes are forecasted to trigger T lymphocytes, B lymphocytes, and immunological memory with overall population coverage above 90%. Accordingly, our in silico vaccine is expected to be the future multi-epitope peptide vaccine against Cryptococcus neoformans var. grubiis heat shock 70KDa protein that covers a significant figure of the entire world citizens. Therefore, there is a definite need for experimental validation for the carefully chosen vaccine candidates in vitro and in vivo to fortify their antigenic and immunogenic potentials. Additionally, further computational studies are needed to be conducted in pathogens-derived Heat shock 70KDa protein family, as it believed to find universal epitopes that might be overlapped with other pathogens-derived Hsp70.",2019-01-29,"Elhassan, R. M.; Alsony, N. M.; Othman, K. M.; Izz-Aldin, D. T.; Alhaj, T. A.; Ali, A. A.; Abashir, L. A.; Ahmed, O. H.; Hassan, M. A.",,,,True
395e8569a0e6fc129029cb0b8cda1f7381954976,biorxiv,Virome heterogeneity and connectivity in waterfowl and shorebird communities,doi.org/10.1101/528174,,,See https://www.biorxiv.org/about-biorxiv,"Models of host-microbe dynamics typically assume a single-host population infected by a single pathogen. In reality, many hosts form multi-species aggregations and may be infected with an assemblage of pathogens. We used a meta-transcriptomic approach to characterize the viromes of nine avian species in the Anseriformes (ducks) and Charadriiformes (shorebirds). This revealed the presence of 27 viral species, of which 24 were novel, including double-stranded RNA viruses (Picobirnaviridae and Reoviridae), single-stranded RNA viruses (Astroviridae, Caliciviridae, Picornaviridae), a retro-transcribing DNA virus (Hepadnaviridae), and a single-stranded DNA virus (Parvoviridae). These viruses comprise multi-host generalist viruses and those that are host-specific, indicative of both virome connectivity and heterogeneity. Virome connectivity was apparent in two well described multi-host virus species (avian coronavirus and influenza A virus) and a novel Rotavirus species that were shared among some Anseriform species, while heterogeneity was reflected in the absence of viruses shared between Anseriformes and Charadriiformes. Notably, within avian host families there was no significant relationship between either host taxonomy or foraging ecology and virome composition, although Anseriform species positive for influenza A virus harboured more additional viruses than those negative for influenza virus. Overall, we demonstrate complex virome structures across host species that co-exist in multi-species aggregations.",2019-01-29,"Wille, M.; Shi, M.; Klaassen, M.; Hurt, A.; Holmes, E.",,,,True
aad76905ce54679c80b75e4ee35717c30e7e1099,biorxiv,Using pan RNA-seq analysis to reveal the ubiquitous existence of 5' and 3' end small RNAs,doi.org/10.1101/444117,,,See https://www.biorxiv.org/about-biorxiv,"In this study, we used pan RNA-seq analysis to reveal the ubiquitous existence of 5 end and 3 end small RNAs. 5 and 3 sRNAs alone can be used to annotate mitochondrial with 1-bp resolution and nuclear non-coding genes and identify new steady-state RNAs, which are usually from functional genes. Using 5, 3 and intronic sRNAs, we revealed that the enzymatic dsRNA cleavage and RNAi could involve in the RNA degradation and gene expression regulation of U1 snRNA in human. The further study of 5, 3 and intronic sRNAs help rediscover double-stranded RNA (dsRNA) cleavage, RNA interference (RNAi) and the regulation of gene expression, which challenges the classical theories. In this study, we provided a simple and cost effective way for the annotation of mitochondrial and nuclear non-coding genes and the identification of new steady-state RNAs, particularly long non-coding RNAs (lncRNAs). We also provided a different point of view for cancer and virus, based on the new discoveries of dsRNA cleavage, RNAi and the regulation of gene expression.",2019-01-31,"Xu, X.; Ji, H.; Cheng, Z.; Jin, X.; Yao, X.; Liu, Y.; Zhao, Q.; Zhang, T.; Ruan, J.; Bu, W.; Chen, Z.; Shan, G.",,,,True
b6d2052bb9aef4f3b1d21e86ca164cd43d020857,biorxiv,Transmission of human-associated microbiota along family and social networks,doi.org/10.1101/540252,,,See https://www.biorxiv.org/about-biorxiv,"The human microbiome, described as an accessory organ because of the crucial functions it provides, is composed of species that are uniquely found in humans1,2. Yet, surprisingly little is known about the impact of routine interpersonal contacts in shaping microbiome composition. In a relatively  closed cohort of 287 people from the Fiji Islands, where common barriers to bacterial transmission are absent, we examine putative bacterial transmission in individuals gut and oral microbiomes using strain-level data from both core SNPs and flexible genomic regions. We find a weak signal of transmission, defined by the inferred sharing of genotypes, across many organisms that, in aggregate, reveals strong transmission patterns, most notably within households and between spouses. We find that women harbor strains more closely related to those harbored by their familial and social contacts than men; and that transmission patterns of oral- and gut-associated microbiota need not be the same. Using strain-level data alone, we are able to confidently predict a subset of spouses, highlighting the role of shared susceptibilities, behaviors or social interactions that distinguish specific links in the social network.",2019-02-05,"Brito, I. L.; Gurry, T.; Zhao, S.; Huang, K.; Young, S.; Shea, T.; Naisilisili, W.; Jenkins, A.; Jupiter, S.; Gevers, D.; Alm, E. J.",,,,True
9ca81dfa68fcbff13166d810aca929027bb3763b,biorxiv,Neural organization of speech production: A lesion-based study of error patterns in connected speech,doi.org/10.1101/544841,,,See https://www.biorxiv.org/about-biorxiv,"While numerous studies have explored single-word naming, few have evaluated the behavioral and neural correlates of more naturalistic language, like connected speech, which we produce every day. Here, in a retrospective analysis of 120 participants at least six months following left hemisphere stroke, we evaluated the distribution of word errors (paraphasias) and associated brain damage during connected speech (picture description) and object naming. While paraphasias in connected speech and naming shared underlying neural substrates, analysis of the distribution of paraphasias suggested that lexical-semantic load is likely reduced during connected speech. Using voxelwise lesion-symptom mapping (VLSM), we demonstrated that verbal (real word: semantically related and unrelated) and sound (phonemic and neologistic) paraphasias during both connected speech and naming loaded onto the left hemisphere ventral and dorsal streams of language, respectively. Furthermore, for the first time using both connected speech and naming data, we localized semantically related paraphasias to more anterior left hemisphere temporal cortex and unrelated paraphasias to more posterior left temporal and temporoparietal cortex. The connected speech results, in particular, highlight a gradient of specificity as one translates visual recognition from left temporo-occipital cortex to posterior and subsequently anterior temporal cortex. The robustness of VLSM results for sound paraphasias derived during connected speech was notable, in that analyses performed on sound paraphasias from the connected speech task, and not the naming task, demonstrated significant results following removal of lesion volume variance and related apraxia of speech variance. Therefore, connected speech may be a particularly sensitive task on which to evaluate further lexical-phonological processing in the brain. The results presented here demonstrate the related, though different, distribution of paraphasias during connected speech, confirm that paraphasias arising in connected speech and single-word naming likely share neural origins, and endorse the need for continued evaluation of the neural substrates of connected speech processes.",2019-02-08,"Stark, B. C.; Basilakos, A.; Hickok, G.; Rorden, C.; Bonilha, L.; Fridriksson, J.",,,,True
661003bddb5c847237ff4a1f34a823f7971e2090,biorxiv,Recombinant vector vaccines and within-host evolution,doi.org/10.1101/545087,,,See https://www.biorxiv.org/about-biorxiv,"Many recombinant vector vaccines are capable of replication within the host. They consist of a fully competent vector backbone engineered to express an antigen from a foreign transgene. From the perspective of viral replication, the transgene is not only dispensable but may even be intrinsically detrimental. Thus vaccine revertants that delete the transgene may evolve to dominate the within-host population and in doing so reduce the antigenicity of the vaccine. We apply mathematical and computational models to study this process, including the dynamics of vaccine and revertant growth plus the dynamics of innate and adaptive immunity. Although the selective basis of vaccine evolution is easy to comprehend, the immunological consequences are not. One complication is that, despite possible fitness differences between vaccine and revertant, the opportunity for vaccine evolution is limited by the short period of growth before the viral population is cleared. Even less obvious, revertant per se does not interfere with immunity to vaccine except as the revertant suppresses vaccine abundance; the magnitude of this interference depends on mechanisms and timing of viral suppression. Adaptive immunity targeting the foreign antigen is also a possible basis of vaccine inferiority, but it is not worsened by vaccine evolution. Overall, we find that within-host vaccine evolution can sometimes matter to the adaptive immune response targeting the foreign antigen, but even when it does matter, simple principles of vaccine design and the control of inoculum composition can largely mitigate the effects.  Author SummaryRecombinant vector vaccines are live replicating viruses that are engineered to carry extra genes derived from a pathogen - and these produce proteins against which we want to generate immunity. These genes may evolve to be lost during the course of replication within an individual, and there is a concern that this can severely limit the vaccines efficacy. The dynamics of this process are studied here with mathematical models. The potential for vaccine evolution is somewhat reduced by the short-term growth of the vaccine population before it is suppressed by the immune response. Even when within-host evolution can be a problem, the models show that increasing the vaccine inoculum size or ensuring that the inoculum is mostly pure vaccine can largely avoid the loss of immunity arising from evolution.",2019-02-08,"Bull, J. J.; Nuismer, S.; Antia, R.",,,,True
f339a22cebc1bc0099beb7aea41be09cc916e5dc,biorxiv,Arenaviridae exoribonuclease presents genomic RNA edition capacity.,doi.org/10.1101/541698,,,See https://www.biorxiv.org/about-biorxiv,"The Arenaviridae is a large family of viruses causing both acute and persistent infections and causing significant public health concerns in afflicted regions. A ""trademark"" of infection is the quick and efficient immuno-suppression mediated in part by a 3-5 RNA exonuclease domain (ExoN) of the Nucleoprotein (NP). Mopeia virus, the eastern African counterpart of Lassa virus, carries such ExoN domain, but does not suppress the host innate immunity. We have recently reported the crystal structure of the Mopeia virus ExoN domain, which presents a conserved fold and active site. In the present study, we show that the ExoN activity rules out a direct link between ExoN activity and alteration of the host innate immunity. We found that the Arenavirus ExoN, however, is able to excise mis-incorporated bases present at the 3-end of double stranded RNA. ExoN(-) arenaviruses cultured in cells dampened in innate immunity still replicated in spite of a significant reduction in the viral charge over several passages. The remaining ExoN(-) virus population showed an increased base substitution rate on a narrow nucleotide spectrum, linking the ExoN activity to genome editing. Since, the Arenavirus ExoN belongs to the same nuclease family as that of the nsp14 coronavirus ExoN ; which has been recently shown to promote viral RNA synthesis proofreading; we propose that Arenavirus ExoN is involved in a ""limited RNA editing"" mechanism mainly controlled by structural constraints and a low mutational/fitness ratio.  Author summaryOnly Arenaviridae and Coronaviridae encode a 3-5 RNA exonuclease domain (ExoN) in their genome. This activity is either used to counteract the innate immunity response during viral infection or to ensure genome stability during replication. Mopeia virus (MOPV), the eastern African counterpart of Lassa virus, carries such ExoN domain, but does not suppress the host innate immunity. We studied MOPV ExoN activity both in vitro and in cellula to assess the role of ExoN MOPV and found that the Arenaviral ExoN is fully active on dsRNA, and is able like the one of Coronaviridae to excise a mismatched base. We measured genetic stability and found evidence of a limited spectrum of RNA synthesis proofreading mechanism, together with a strongly impacted viral replication. We propose that the Arenaviral ExoN is involved in a functional check of the conserved RNA structures of the viral genome.",2019-02-13,"Yekwa, E.; Aphibanthammakit, C.; Carnec, X.; Picard, C.; Canard, B.; Baize, S.; Ferron, F.",,,,True
1c66ec8950cbd1e0f0d4bc4a43ba9c79411cc5fa,biorxiv,Critical Nodes of Virus-Host Interaction Revealed Through an Integrated Network Analysis,doi.org/10.1101/548909,,,See https://www.biorxiv.org/about-biorxiv,"Viruses are one of the major causes of various acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signalling pathways. A collective view of these multiple studies could advance our understanding of viral evasion mechanisms and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.",2019-02-13,"Bosl, K.; Ianevski, A.; Than, T. T.; Andersen, P. I.; Kuivanen, S.; Teppor, M.; Zusinaite, E.; Dumpis, U.; Vitkauskiene, A.; Cox, R. J.; Kallio-Kokko, H.; Bergqvist, A.; Tenson, T.; Oksenych, V.; Bjoras, M.; Anthonsen, M. W.; Shum, D.; Kaarbo, M.; Vapalahti, O.; Windisch, M. P.; Superti-Furga, G.; Snijder, B.; Kainov, D.; Kandasamy, R. K.",,,,True
f53e10f9cd4b97134ded58b3de4bcc36a55304d3,biorxiv,A specific sequence in the genome of respiratory syncytial virus regulates the generation of copy-back defective viral genomes,doi.org/10.1101/349001,,,See https://www.biorxiv.org/about-biorxiv,"Defective viral genomes of the copy-back type (cbDVGs) are the primary initiators of the antiviral immune response during infection with respiratory syncytial virus (RSV) both in vitro and in vivo. However, the mechanism governing cbDVG generation remains unknown, thereby limiting our ability to manipulate cbDVG content in order to modulate the host response to infection. Here we report a specific genomic signal that mediates the generation of RSV cbDVGs. Using a customized bioinformatics tool, we identified regions in the RSV genome frequently used to generate cbDVGs during infection. We then created a minigenome system to validate the function of one of these sequences and to determine if specific nucleotides were essential for cbDVG generation at that position. Further, we created a recombinant virus that selectively produced a specific cbDVG based on variations introduced in this sequence. The identified sequence was also found as a common site for cbDVG generation during natural RSV infections, and common cbDVGs generated at this sequence were found among samples from various infected patients. These data demonstrate that sequences encoded in the viral genome are critical determinants of the location of cbDVG generation and, therefore, this is not a stochastic process. Most importantly, these findings open the possibility of genetically manipulating cbDVG formation to modulate infection outcome.  Author summaryCopy-back defective viral genomes (cbDVGs) regulate infection and pathogenesis of Mononegavirales. cbDVG are believed to arise from random errors that occur during virus replication and the predominant hypothesis is that the viral polymerase is the main driver of cbDVG generation. Here we describe a specific genomic sequence in the RSV genome that is necessary for the generation of a large proportion of the cbDVG population present during infection. We identified specific nucleotides that when modified altered cbDVG generation at this position, and we created a recombinant virus that selectively produced cbDVGs based on mutations in this sequence. These data demonstrate that the generation of RSV cbDVGs is regulated by specific viral sequences and that these sequences can be manipulated to alter the content and quality of cbDVG generated during infection.",2019-02-15,"Sun, Y.; Kim, E.; Felt, S. A.; Taylor, L.; Agarwal, D.; Grant, G.; Lopez, C.",,,,True
77a04c5091c0457ad305691d4d4f24354d6bae79,biorxiv,Structure of the SARS-CoV NSP12 polymerase bound to NSP7 and NSP8 co-factors,doi.org/10.1101/551986,,,See https://www.biorxiv.org/about-biorxiv,"Recent history is punctuated by the emergence of highly pathogenic coronaviruses such as SARS- and MERS-CoV into human circulation. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (NSP) responsible for the replication and transcription of the viral genome. Here, we present the 3.1 [A] resolution structure of the SARS-CoV NSP12 polymerase bound to its essential co-factors, NSP7 and NSP8, using single particle cryo-electron microscopy. NSP12 possesses an architecture common to all viral polymerases as well as a large N-terminal extension containing a kinase-like fold and is unexpectedly bound by two NSP8 co-factors. This structure illuminates the assembly of the coronavirus core RNA-synthesis machinery, provides key insights into NSP12 polymerase catalysis and fidelity and acts as a template for the design of novel antiviral therapeutics.",2019-02-15,"Kirchdoerfer, R. N.; Ward, A. B.",,,,True
d8c2466863d8ff87bc1aaf5218ce6f3f7fb29c3b,biorxiv,Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques,doi.org/10.1101/552356,,,See https://www.biorxiv.org/about-biorxiv,"Social experiences are an important predictor of disease susceptibility and survival in humans and other social mammals. Chronic social stress is thought to generate a pro-inflammatory state characterized by elevated antibacterial defenses and reduced investment in antiviral defense. Here, we manipulated long-term social status in female rhesus macaques to show that social subordination alters the gene expression response to ex vivo bacterial and viral challenge. As predicted by current models, bacterial lipopolysaccharide polarizes the immune response such that low status corresponds to higher expression of genes in NF-{kappa}B-dependent pro-inflammatory pathways and lower expression of genes involved in the antiviral response and type I interferon (IFN) signaling. Counter to predictions, however, low status drives more exaggerated expression of both NF-{kappa}B and IFN-associated genes after cells are exposed to the viral mimic Gardiquimod. Status-driven gene expression patterns are not only linked to social status at the time of sampling, but also to social history (i.e., past social status), especially in unstimulated cells. However, for a subset of genes, we observed interaction effects in which females who fell in rank were more strongly affected by current social status than those who climbed the social hierarchy. Together, our results indicate that the effects of social status on immune cell gene expression depend on pathogen exposure, pathogen type, and social history - in support of social experience-mediated biological embedding in adulthood, even in the conventionally memory-less innate immune system.",2019-02-18,"Sanz, J.; Maurizio, P. L.; Snyder-Mackler, N.; Simons, N. D.; Voyles, T.; Kohn, J.; Michopoulos, V.; Wilson, M.; Tung, J.; Barreiro, L. B.",,,,True
368fb114dfd565dedb635f62b9062956b49cd475,biorxiv,Anti-biofilm Activity of Graphene Quantum Dots via Self-Assembly with Bacterial Amyloid Proteins,doi.org/10.1101/550285,,,See https://www.biorxiv.org/about-biorxiv,"Bacterial biofilms represent an essential part of Earths ecosystem that can cause multiple ecological, technological and health problems. The environmental resilience and sophisticated organization of biofilms are enabled by the extracellular matrix that creates a protective network of biomolecules around the bacterial community. Current anti-biofilm agents can interfere with extracellular matrix production but, being based on small molecules, are degraded by bacteria and rapidly diffuse away from biofilms. Both factors severely reduce their efficacy, while their toxicity to higher organisms create additional barriers to their practicality. In this paper we report on the ability of graphene quantum dots to effectively disperse mature Staphylococcus aureus biofilms, interfering with the self-assembly of amyloid fibers - a key structural component of the extracellular matrix. Mimicking peptide-binding biomolecules, graphene quantum dots form supramolecular complexes with phenol soluble modulins, the peptide monomers of amyloid fibers. Experimental and computational results show that graphene quantum dots efficiently dock near the N-terminus of the peptide and change the secondary structure of phenol soluble modulins, which disrupts their fibrillation and represents a novel strategy for mitigation of bacterial communities.  O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC=""FIGDIR/small/550285v1_ufig1.gif"" ALT=""Figure 1""> View larger version (17K): org.highwire.dtl.DTLVardef@a94402org.highwire.dtl.DTLVardef@b009b3org.highwire.dtl.DTLVardef@14cfb70org.highwire.dtl.DTLVardef@10f8e52_HPS_FORMAT_FIGEXP  M_FIG GQD mediated staphylococcal biofilm dispersal. GQDs interact with PSM peptides and frustrate the fibrillation process. The reduction in amyloid fibers prevents robust stabilization of the biofilm. In addition, there is an increase in free monomeric and oligomeric PSM peptides which trigger dispersal events.  C_FIG",2019-02-19,"Wang, Y.; Kadiyala, U.; Qu, Z.; Elvati, P.; Altheim, C.; Kotov, N. A.; Violi, A.; VanEpps, J. S.",,,,True
8e830dc6cb2de091920ff5b3b14f806a61a8aef4,biorxiv,Mammalian orthoreovirus infection is enhanced in cells pre-treated with sodium arsenite,doi.org/10.1101/555367,,,See https://www.biorxiv.org/about-biorxiv,"Following reovirus infection, cells activate stress responses that repress canonical cellular translation as a mechanism to limit production of progeny virions. This includes the formation of stress granules (SG) that sequester translationally-stalled cellular transcripts, translation initiation factors, ribosomal proteins, and RNA binding proteins until conditions improve and translation can resume. Work by others suggests that these cellular stress responses, which are part of the integrated stress response, may benefit rather than repress reovirus replication. In agreement with this, we report that stressing cells prior to infection with sodium arsenite (SA), a robust inducer of SG and activator of eIF2 kinases, enhanced viral protein expression, percent infectivity and viral titer in SA-treated cells compared to untreated cells. SA-mediated enhancement of reovirus replication was not strain-specific, but was cell-type specific. While pre-treatment of cells with SA offered the greatest enhancement, treatment of infected cultures as late as 4 h post infection resulted in an increase in the percent of cells infected. SA activates the HRI kinase, which phosphorylates eIF2 and subsequently induces SG formation. Other stresses, such as heat shock (HS) and osmotic shock also activate HRI. Heat shock of cells prior to reovirus infection readily induced SG in greater than 85% of cells. Although HS pre-treatment had no effect on the percentage of infected cells or viral yield, it did enhance viral protein expression. These data suggest that SA pre-treatment perturbs the cell in a way that is beneficial for reovirus and that neither HRI activation nor SG induction is sufficient for reovirus infection enhancement.  SIGNIFICANCEAll viruses rely on the host translational machinery for the synthesis of viral proteins. In response to viral infection, cells activate the integrated stress response resulting in the phosphorylation of eIF2 and translation shutoff. Despite this, reovirus replicates to reduced titers in the absence of this response. In this work, we report that sodium arsenite activation of the integrated stress response prior to virus inoculation enhances virus infectivity, protein expression and titer. Together, these data suggest that modulation of conserved cellular stress responses can alter reovirus replication.",2019-02-20,"Lutz, M. M.; Worth, M. P.; Hinchman, M. M.; Parker, J. S. L.; Ledgerwood, E. D.",,,,True
9261e7a9a4d3febda29d574074a79f02376249a3,biorxiv,Intrinsic checkpoint deficiency during cell cycle re-entry from quiescence,doi.org/10.1101/558783,,,See https://www.biorxiv.org/about-biorxiv,"The authors find that human cells re-entering the cell cycle from quiescence have both an impaired p53-dependent DNA replication origin licensing checkpoint and slow origin licensing. This combination makes every first S phase underlicensed and hypersensitive to replication stress.  ABSTRACTTo maintain tissue homeostasis, cells transition between cell cycle quiescence and proliferation. An essential G1 process is Minichromosome Maintenance complex (MCM) loading at DNA replication origins to prepare for S phase, known as origin licensing. A p53-dependent origin licensing checkpoint normally ensures sufficient MCM loading prior to S phase entry. We used quantitative flow cytometry and live cell imaging to compare MCM loading during the long first G1 upon cell cycle entry and the shorter G1 phases in the second and subsequent cycles. We discovered that despite the longer G1 phase, the first G1 after cell cycle re-entry is significantly underlicensed. As a result, the first S phase cells are hypersensitive to replication stress. This underlicensing is from a combination of slow MCM loading with a severely compromised origin licensing checkpoint. The hypersensitivity to replication stress increases over repeated rounds of quiescence. Thus, underlicensing after cell cycle re-entry from quiescence distinguishes a higher risk cell cycle that promotes genome instability.",2019-02-22,"Matson, J. P.; House, A. M.; Grant, G. D.; Wu, H.; Perez, J.; Cook, J.",,,,True
ff6c0b549e3f20ec78845f981f19687eece4addf,biorxiv,Increased Neurite Orientation-Dispersion and Density in the TgCRND8 Mouse Model of Amyloidosis: Inverse Relation with Functional Connectome Clustering and Modulation by Interleukin-6,doi.org/10.1101/562348,,,See https://www.biorxiv.org/about-biorxiv,"Extracellular {beta}-amyloid (A{beta}) plaque deposits and inflammatory immune activation are thought to alter various aspects of tissue microstructure, such as extracellular free water, fractional anisotropy and diffusivity, as well as the density and geometric arrangement of axonal processes. Quantifying these microstructural changes in Alzheimers disease and related neurodegenerative dementias could serve to accurately monitor or predict disease course. In the present study we used high-field diffusion magnetic resonance imaging (dMRI) to determine how A{beta} and inflammatory interleukin-6 (IL6), alone or in combination, affect in vivo tissue microstructure in the TgCRND8 mouse model of Alzheimers-type A{beta} deposition. TgCRND8 and non-transgenic (nTg) mice expressing brain-targeted IL6 or enhanced glial fibrillary protein (EGFP controls) were scanned at 8 months of age using a 2-shell, 54-gradient direction dMRI sequence at 11.1 Tesla. Images were processed using the free water elimination method and the neurite orientation dispersion and density imaging (NODDI) model. DTI and NODDI processing in TgCRND8 mice revealed a microstructure pattern consistent with reduced white matter integrity along with an increase in density and geometric complexity of axonal and dendritic processes. This included reduced FA, mean diffusivity (MD), and free water (FW), and increased  neurite density (NDI) and orientation dispersion (ODI). IL6 produced a  protective-like effect on FA in TgCRND8 mice, although there were minimal microstructure changes in these mice compared IL6 expressing nTg mice. In addition, we found that NDI and ODI had an inverse relationship with the functional connectome clustering coefficient, which was affected by A{beta} and IL6. The relationship between NODDI and graph theory metrics suggests that increasing the density and orientation dispersion of neurites may relate to diminished functional network organization in the brain.",2019-02-27,"Colon-Perez, L. M.; Ibanez, K. R.; Suarez, M. R.; Torroella, K.; Acuna, K. R.; Ofori, E.; Levites, Y. R.; Vaillancourt, D. E.; Golde, T. E.; Chakrabarty, P.; Febo, M.",,,,True
ea7cf2347337e379e62c9bf09b2db9b44fb2e812,biorxiv,Novel Function of Bluetongue Virus NS3 Protein in Regulation of the MAPK/ERK Signaling Pathway,doi.org/10.1101/562421,,,See https://www.biorxiv.org/about-biorxiv,"Bluetongue virus (BTV) is an arbovirus transmitted by blood-feeding midges to a wide range of wild and domestic ruminants. In this report, we showed that BTV, through its virulence non-structural protein NS3 (BTV-NS3), is able to activate the MAPK/ERK pathway. In response to growth factors, the MAPK/ERK pathway activates cell survival, differentiation, proliferation and protein translation but can also lead to the production of several inflammatory cytokines. By combining immunoprecipitation of BTV-NS3 and mass spectrometry analysis from both BTV-infected and NS3-transfected cells, we identified the serine/threonine-protein kinase B-Raf (BRAF), a crucial player of the MAPK/ERK pathway, as a new cellular interactor of BTV-NS3. BRAF silencing led to a significant decrease of the MAPK/ERK activation by BTV supporting a model where BTV-NS3 interacts with BRAF to activate this signaling cascade. Furthermore, the intrinsic ability of BTV-NS3 to bind BRAF and activate the MAPK/ERK pathway is conserved throughout multiple serotypes/strains but appears to be specific to BTV compared to other members of Orbivirus genus. Inhibition of MAPK/ERK pathway with U0126 reduced viral titers, suggesting that BTV manipulates this pathway for its own replication. Therefore, the activation of the MAPK/ERK pathway by BTV-NS3 could benefit to BTV replication by promoting its own viral protein synthesis but could also explain the deleterious inflammation associated with tissue damages as already observed in severe cases of BT disease. Altogether, our data provide molecular mechanisms to explain the role of BTV-NS3 as a virulence factor and determinant of pathogenesis.  ImportanceBluetongue Virus (BTV) is responsible of the non-contagious arthropod-borne disease Bluetongue (BT) transmitted to ruminants by blood-feeding midges. Despite the fact that BTV has been extensively studied, we still have little understanding of the molecular determinants of BTV virulence. In this report, we found that the virulence protein NS3 interacts with BRAF, a key component of the MAPK/ERK pathway. In response to growth factors, this pathway promotes cell survival, increases protein translation but also contributes to the production of inflammatory cytokines. We showed that BTV-NS3 enhances the MAPK/ERK pathway and this activation is BRAF-dependent. Our results demonstrate, at the molecular level, how a single virulence factor has evolved to target a cellular function to ensure its viral replication. On the other hand, our findings could also explain the deleterious inflammation associated with tissue damages as already observed in severe cases of BT disease.",2019-02-27,"Kundlacz, C.; Pourcelot, M.; Fablet, A.; Amaral Da Silva Moraes, R.; Leger, T.; Morlet, B.; Viarouge, C.; Sailleau, C.; Turpaud, M.; Gorlier, A.; Breard, E.; Lecollinet, S.; van Rijn, P. A.; Zientara, S.; Vitour, D.; Caignard, G.",,,,True
683416e300a4f4075835852558855b07c342bd72,biorxiv,Glycosylation of Zika Virus Is Important in Host-Virus Interaction and Pathogenesis,doi.org/10.1101/564542,,,See https://www.biorxiv.org/about-biorxiv,"Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults. Because ZIKV uses glycosylation of its envelope (E) protein to interact with host cell receptors to facilitate entry, these interactions could also be important for designing therapeutics and vaccines. Due to a lack of information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells. ZIKV E proteins are extensively modified with oligomannose-, hybrid- and complex-N-glycans of a highly heterogeneous nature. Host cell-surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we discovered that ZIKV N-glycans are important in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate cell entry of ZIKV. Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.",2019-03-01,"Routhu, N. K.; Lehoux, S. D.; Rouse, E. A.; Bidokhti, M. R. M.; Giron, L. B.; Anzurez, A.; Reid, S. P.; Abdel-Mohsen, M.; Cummings, R. D.; Byrareddy, S. N.",,,,True
e901cf35efbad09a224f2c500f7aef1f6d2d3b6a,biorxiv,How to make more from exposure data? An integrated machine learning pipeline to predict pathogen exposure,doi.org/10.1101/569012,,,See https://www.biorxiv.org/about-biorxiv,"O_LIPredicting infectious disease dynamics is a central challenge in disease ecology. Models that can assess which individuals are most at risk of being exposed to a pathogen not only provide valuable insights into disease transmission and dynamics but can also guide management interventions. Constructing such models for wild animal populations, however, is particularly challenging; often only serological data is available on a subset of individuals and non-linear relationships between variables are common.\nC_LIO_LIHere we take advantage of the latest advances in statistical machine learning to construct pathogen-risk models that automatically incorporate complex non-linear relationships with minimal statistical assumptions from ecological data with missing values. Our approach compares multiple machine learning algorithms in a unified environment to find the model with the best predictive performance and uses game theory to better interpret results. We apply this framework on two major pathogens that infect African lions: canine distemper virus (CDV) and feline parvovirus.\nC_LIO_LIOur modelling approach provided enhanced predictive performance compared to more traditional approaches, as well as new insights into disease risks in a wild population. We were able to efficiently capture and visualise strong non-linear patterns, as well as model complex interactions between variables in shaping exposure risk from CDV and feline parvovirus. For example, we found that lions were more likely to be exposed to CDV at a young age but only in low rainfall years.\nC_LIO_LIWhen combined with our data calibration approach, our framework helped us to answer questions about risk of pathogen exposure which are difficult to address with previous methods. Our framework not only has the potential to aid in predicting disease risk in animal populations, but also can be used to build robust predictive models suitable for other ecological applications such as modelling species distribution or diversity patterns.\nC_LI",2019-03-06,"Fountain-Jones, N.; Machado, G.; Carver, S.; Packer, C.; Mendoza, M.; Craft, M. E.",,,,True
c72595eda8a721e9bff19fcc18ecbb8510054f37,biorxiv,Identification of the relative timing of infectiousness and symptom onset for outbreak control,doi.org/10.1101/571547,,,See https://www.biorxiv.org/about-biorxiv,"In an outbreak of an emerging disease the epidemiological characteristics of the pathogen may be largely unknown. A key determinant of ability to control the outbreak is the relative timing of infectiousness and symptom onset. We provide a method for identifying this relationship with high accuracy based on data from household-stratified symptom-onset data. Further, this can be achieved with observations taken on only a few specific days, chosen optimally, within each household. This constitutes an important tool for outbreak response. An accurate and computationally-efficient heuristic for determining the optimal surveillance scheme is introduced. This heuristic provides a novel approach to optimal design for Bayesian model discrimination.",2019-03-08,"Cope, R. C.; Ross, J. V.",,,,True
ed0a318f34fe2d65cce6127be009ad7d5f3c7cae,biorxiv,Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation.,doi.org/10.1101/571455,,,See https://www.biorxiv.org/about-biorxiv,"Knowledge of the host factors required for norovirus replication has been hindered by the challenges associated with culturing human noroviruses. We have combined proteomic analysis of the viral translation and replication complexes with a CRISPR screen, to identify host factors required for norovirus infection. The core stress granule component G3BP1 was identified as a host factor essential for efficient human and murine norovirus infection, demonstrating a conserved function across the Norovirus genus. Furthermore, we show that G3BP1 functions in the novel paradigm of viral VPg-dependent translation initiation, contributing to the assembly of translation complexes on the VPg-linked viral positive sense RNA genome by facilitating 40S recruitment. Our data suggest that G3BP1 functions by providing viral RNA a competitive advantage over capped cellular RNAs, uncovering a novel function for G3BP1 in the life cycle of positive sense RNA viruses and identifying the first host factor with pan-norovirus pro-viral activity.",2019-03-08,"Hosmillo, M.; Lu, J.; McAllaster, M. R.; Eaglesham, J. B.; Wang, X.; Emmott, E.; Domingues, P.; Chaudhry, Y.; Fitzmaurice, T. J.; Tung, M. K. H.; Panas, M.; McInerney, G.; Locker, N.; Willen, C. B.; Goodfellow, I.",,,,True
d485fce0c7ad92a1e1606eb81043bf9e12714562,biorxiv,"Realized generation times: contraction and impact of infectious period, reproduction number and population size",doi.org/10.1101/568485,,,See https://www.biorxiv.org/about-biorxiv,"One of the key characteristics of the transmission dynamics of infectious diseases is the generation time which refers to the time interval between the infection of a secondary case and the infection of its infector. The generation time distribution together with the reproduction number determines the rate at which an infection spreads in a population. When defining the generation time distribution at a calendar time t two definitions are plausible according whether we regard t as the infection time of the infector or the infection time of the infectee. The resulting measurements are respectively called forward generation time and backward generation time. It has been observed that the mean forward generation time contracts around the peak of an epidemic. This contraction effect has previously been attributed to either competition among potential infectors or depletion of susceptibles in the population. The first explanation requires many infectives for contraction to occur whereas the latter explanation suggests that contraction occurs even when there are few infectives. With a simulation study we show that both competition and depletion cause the mean forward generation time to contract. Our results also reveal that the distribution of the infectious period and the reproduction number have a strong effect on the size and timing of the contraction, as well as on the mean value of the generation time in both forward and backward scheme.\n\nAuthor summaryInfectious diseases remain one of the greatest threats to human health and commerce, and the analysis of epidemic data is one of the most important applications of statistics in public health. Thus, having reliable estimates of fundamental infectious diseases parameters is critical for public health decision-makers in order to take appropriate actions for the global prevention and management of outbreaks and other health emergencies. A key example is given by the prediction models of the reproduction numbers: these rely on the generation time distribution that is usually estimated from contact tracing data collected at a precise calendar time. The forward scheme is used in such a prediction model and the knowledge of its evolution over time is crucial to correctly estimate the parameters of interest. It is therefore important to characterize the causes that lead to the contraction of the mean forward generation time during the course of an outbreak.\n\nIn this paper, we firstly identify the impact of the epidemiological quantities as reproduction number, infectious period and population size on the mean forward and backward generation time. Moreover, we analyze the phenomena of competition among infectives and depletion of susceptible individuals highlighting their effects on the contraction of the mean forward generation time. The upshot of this investigation is that the variance of the infectious period distribution and the reproduction number have a strong impact on the generation times affecting both the mean value and the evolution over time. Furthermore, competition and depletion can both cause contraction even for small values of the reproduction number suggesting that, in epidemic models where the generation time is considered time-inhomogeneous, estimators accounting for both depletion and competing risks are to be preferred in the inference of the generation interval distributions.",2019-03-08,"Torneri, A.; Azmon, A.; Faes, C.; Kenah, E.; Scalia Tomba, G.; Wallinga, J.; Hens, N.",,,,True
bd872a86902d848bd94694469bb0c5cb05bea483,biorxiv,A systematic review of MERS-CoV (Middle East Respiratory Syndrome Coronavirus) seroprevalence and viral RNA prevalence in dromedary camels: implications for animal vaccination,doi.org/10.1101/574103,,,See https://www.biorxiv.org/about-biorxiv,"Human infection with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is driven by recurring dromedary-to-human spill-over events, leading decision-makers to consider dromedary vaccination. Dromedary vaccine candidates in the development pipeline are showing hopeful results, but gaps in our understanding of the epidemiology of MERS-CoV in dromedaries must be addressed to design and evaluate potential vaccination strategies. We systematically reviewed the published literature reporting seroprevalence and/or prevalence of active MERS-CoV infection in dromedary populations from both cross-sectional and longitudinal studies, including 60 studies in our qualitative syntheses. MERS-CoV seroprevalence increased with age up to 80-100% in adult dromedaries supporting geographically wide spread endemicity of MERS-CoV in dromedaries in both the Arabian Peninsula and countries exporting dromedaries from Africa. The high prevalence of active infection measured in juveniles and at sites where dromedary populations mix should guide further investigation - particularly of dromedary movement - and inform vaccination strategy design.",2019-03-11,"Dighe, A.; Jombart, T.; Van Kerkhove, M. D.; Ferguson, N.",,,,True
552548a4e9a576953acad9fa549ec4d796fe52c9,biorxiv,Synergetic effect of non-complementary 5’ AT-rich sequences on the development of a multiplex TaqMan real-time PCR for specific and robust detection of Clavibacter michiganensis and C. michiganensis subsp. nebraskensis,doi.org/10.1101/566281,,,See https://www.biorxiv.org/about-biorxiv,"Clavibacter is an agriculturally important genus comprising a single species, Clavibacter michiganensis, and multiple subspecies, including, C. michiganensis subsp. nebraskensis which causes Gosss wilt/blight of corn and accounts for high yield losses - listed among the five most significant diseases of corn in the United States of America. Our research objective was to develop a robust and rapid multiplex TaqMan real-time PCR (qPCR) to detect C. michiganensis in general and C. michiganensis subsp. nebraskensis with enhanced reliability and accuracy by adding non-complementary AT sequences to the 5 end of the forward and reverse primers. Comparative genomic analyses were performed to identify unique and conserved gene regions for primer and probe design. The unique genomic regions, ABC transporter ATP-binding protein CDS/ABC-transporter permease and MFS transporter were determined for specific detection of C. michiganensis and C. m. subsp. nebraskensis, respectively. The AT-rich sequences at the 5 position of the primers enhanced the reaction efficiency and sensitivity of rapid qPCR cycling; the reliability, accuracy and high efficiency of the developed assay was confirmed after testing with 59 strains from inclusivity and exclusivity panels - no false positives or false negatives were detected. The assays were also validated through naturally and artificially infected corn plant samples; all samples were detected for C. michiganensis and C. m. subsp. nebraskensis with 100% accuracy. The assay with 5 AT-rich sequences detected up to 10- and 100-fg of C. michiganensis and C. michiganensis subsp. nebraskensis genome targets, respectively. No adverse effect was observed when sensitivity assays were spiked with host genomic DNA. Addition of 5 AT rich sequences enhanced the qPCR reaction efficiency from 0.82 (M = -3.83) and 0.91 (M = -3.54) to 1.04 (with optimum slope value; M = -3.23) for both C. michiganensis and C. michiganensis subsp. nebraskensis, respectively; a increase of 10-fold sensitivity was also obtained with C. michiganensis primer set. The methodology proposed here can be used to optimize the reaction efficiency and to harmonize the diagnostic protocols which have prodigious applications in routine diagnostics, biosecurity and microbial forensics.",2019-03-11,"Larrea-Sarmiento, A.; Alvarez, A. M.; Stack, J. P.; Arif, M.",,,,True
55e0d20b6cc56c2cdc131e1dcc51f752575cf532,biorxiv,Stress-Induced Transcriptional Memory Accelerates Promoter-Proximal Pause-Release and Decelerates Termination over Mitotic Divisions,doi.org/10.1101/576959,,,See https://www.biorxiv.org/about-biorxiv,"Heat shock triggers an instant reprogramming of gene and enhancer transcription, but whether cells encode a memory to stress, at the level of nascent transcription, has remained unknown. Here, we measured transcriptional response to acute heat stress in unconditioned cells and in daughters of cells that had been exposed to a single or multiple heat shocks. Tracking RNA Polymerase II (Pol II) genome-wide at nucleotide-resolution revealed that cells precisely remember their transcriptional identity throughout stress, restoring Pol II distribution at gene bodies and enhancers upon recovery. However, single heat shock primed faster gene-induction in the daughter cells by increasing promoter-proximal Pol II pausing, and accelerating the pause-release. In repeatedly stressed cells, both basal and inducible transcription was refined, and pre-mRNA processing decelerated, which retained transcripts on chromatin and reduced recycling of the transcription machinery. These results mechanistically uncovered how the steps of pause-release and termination maintain transcriptional memory over mitosis.\n\nHighlights-Cell type-specific transcription precisely recovers after heat-induced reprogramming\n-Single heat shock primes genes for accelerated induction over mitotic divisions via increased promoter-proximal Pol II pausing and faster pause-release\n-Multiple heat shocks refine basal and inducible transcription over mitotic divisions to support survival of the daughter cells\n-Decelerated termination at active genes reduces recycling of Pol II to heat-activated promoters and enhancers\n-HSF1 increases the rate of promoter-proximal pause-release via distal and proximal regulatory elements",2019-03-14,"Vihervaara, A.; Mahat, D. B.; Himanen, S. V.; Blom, M. A. H.; Lis, J. T.; Sistonen, L.",,,,True
518b635f78bdc65dc6666380eafc3b7a283b3af7,biorxiv,Tissue Tropism and Transmission Ecology Predict Virulence of Human RNA Viruses,doi.org/10.1101/581512,,,See https://www.biorxiv.org/about-biorxiv,"Novel infectious diseases continue to emerge within human populations. Predictive studies have begun to identify pathogen traits associated with emergence. However, emerging pathogens vary widely in virulence, a key determinant of their ultimate risk to public health. Here, we use structured literature searches to review the virulence of each of the 214 known human-infective RNA virus species. We then use a machine learning framework to determine whether viral virulence can be predicted by ecological traits including human-to-human transmissibility, transmission routes, tissue tropisms and host range. Using severity of clinical disease as a measurement of virulence, we identified potential risk factors using predictive classification tree and random forest ensemble models. The random forest model predicted literature-assigned disease severity of test data with 90.3% accuracy, compared to a null accuracy of 74.2%. In addition to viral taxonomy, the ability to cause systemic infection, having renal and/or neural tropism, direct contact or respiratory transmission, and limited (0 < R0 [&le;] 1) human-to-human transmissibility were the strongest predictors of severe disease. We present a novel, comparative perspective on the virulence of all currently known human RNA virus species. The risk factors identified may provide novel perspectives in understanding the evolution of virulence and elucidating molecular virulence mechanisms. These risk factors could also improve planning and preparedness in public health strategies as part of a predictive framework for novel human infections.\n\nAuthor SummaryNewly emerging infectious diseases present potentially serious threats to global health. Although studies have begun to identify pathogen traits associated with the emergence of new human diseases, these do not address why emerging infections vary in the severity of disease they cause, often termed  virulence. We test whether ecological traits of human viruses can act as predictors of virulence, as suggested by theoretical studies. We conduct the first systematic review of virulence across all currently known human RNA virus species. We adopt a machine learning approach by constructing a random forest, a model that aims to optimally predict an outcome using a specific structure of predictors. Predictions matched literature-assigned ratings for 28 of 31 test set viruses. Our predictive model suggests that higher virulence is associated with infection of multiple organ systems, nervous systems or the renal systems. Higher virulence was also associated with contact-based or airborne transmission, and limited capability to transmit between humans. These risk factors may provide novel starting points for questioning why virulence should evolve and identifying causative mechanisms of virulence. In addition, our work could suggest priority targets for infectious disease surveillance and future public health risk strategies.\n\nBlurbComparative analysis using machine learning shows specificity of tissue tropism and transmission biology can act as predictive risk factors for virulence of human RNA viruses.",2019-03-19,"Brierley, L.; Pedersen, A. B.; Woolhouse, M. E. J.",,,,True
5d768aca47f1452fd3e3d2c246926b8532ca1c87,biorxiv,Comparison of real-time PCR and droplet digital PCR for the detection of Xylella fastidiosa in plants,doi.org/10.1101/582288,,,See https://www.biorxiv.org/about-biorxiv,"Xylella fastidiosa (Xf) is a quarantine plant pathogen bacterium originating from the Americas and that has emerged in Europe in 2013. Xf can be detected directly on plant macerate using molecular methods such as real-time PCR, which is a sensitive technique. However, some plants may contain components that can act as PCR reaction inhibitors, which can lead to false negative results or an underestimation of the bacterial concentration present in the analyzed plant sample. Droplet digital PCR (ddPCR) is an innovative tool based on the partitioning of the PCR reagents and the DNA sample into thousands of droplets, allowing the quantification of the absolute number of target DNA molecules present in a reaction mixture, or an increase of the detection sensitivity. In this study, a real-time PCR protocol, already used for Xf detection in the framework of official surveys in the European Union, was transferred and optimized for Xf detection using ddPCR. This new assay was evaluated and compared to the initial real-time PCR on five plant matrices artificially inoculated and on naturally infected plants. In our conditions, this new ddPCR enabled the detection of Xf on all artificially inoculated plant macerates with a similar limit of detection, or a slight benefit for Quercus ilex. Moreover, ddPCR improved diagnostic sensitivity as it enabled detection of Xf in samples of Polygala myrtifolia or Q. ilex that were categorized as negative or close to the limit of detection using the real-time PCR. Here, we report for the first time a ddPCR assay for the detection of the bacterium Xf.",2019-03-20,"Dupas, E.; Legendre, B.; Olivier, V.; Poliakoff, F.; Manceau, C.; Cunty, A.",,,,True
acd5cb2ba08da5c0f6bc310d74d497d38aa86be2,biorxiv,Enhanced replication of mouse adenovirus type 1 following virus-induced degradation of protein kinase R (PKR),doi.org/10.1101/584680,,,See https://www.biorxiv.org/about-biorxiv,"Protein kinase R (PKR) plays a major role in activating host immunity during infection by sensing dsRNA produced by viruses. Once activated by dsRNA, PKR phosphorylates the translation factor eIF2, halting cellular translation. Many viruses have methods of inhibiting PKR activation or its downstream effects, circumventing protein synthesis shutdown. These include sequestering dsRNA or producing proteins that bind to and inhibit PKR activation. Here we describe our finding that in multiple cell types, PKR was depleted during mouse adenovirus type 1 (MAV-1) infection. MAV-1 did not appear to be targeting PKR at a transcriptional or translational level because total PKR mRNA levels and levels of PKR mRNA bound to polysomes were unchanged or increased during MAV-1 infection. However, inhibiting the proteasome reduced the PKR depletion seen in MAV-1-infected cells, whereas inhibiting the lysosome had no effect. This suggests that proteasomal degradation alone is responsible for PKR degradation during MAV-1 infection. Time course experiments indicate that the degradation occurs early after infection. Infecting cells with UV-inactivated virus prevented PKR degradation, whereas inhibiting viral DNA replication did not. Together these results suggest that an early viral gene is responsible. Degradation of PKR is a rare mechanism to oppose PKR activity, and it has only been described in six RNA viruses. To our knowledge, this is the first example of a DNA virus counteracting PKR by degrading it.\n\nImportanceThe first line of defense in cells during viral infection is the innate immune system, which is activated by different viral products. PKR is a part of this innate immune system and is induced by interferon and activated by dsRNA produced by DNA and RNA viruses. PKR is such an important part of the antiviral response that many viral families have gene products to counteract its activation or the resulting effects of its activity. Although a few RNA viruses degrade PKR, this method of counteracting PKR has not been reported for any DNA viruses. MAV-1 does not encode virus-associated RNAs, a human adenoviral defense against PKR activation. Instead, MAV-1 degrades PKR, and it is the first DNA virus reported to do so. The innate immune evasion by PKR degradation is a previously unidentified way for a DNA virus to circumvent the host antiviral response.",2019-03-21,"Goodman, D. E.; Pretto-Kernahan, C. D.; Krepostman, T. A.; Carnahan, K. E.; Spindler, K. R.",,,,True
123db7cdec9fc63aa09782ea9f4267603be8f74d,biorxiv,DNA-scaffolded biomaterials enable modular and tunable control of cell-based cancer immunotherapies,doi.org/10.1101/587105,,,See https://www.biorxiv.org/about-biorxiv,"Advanced biomaterials provide versatile ways to spatially and temporally control immune cell activity, potentially enhancing their therapeutic potency and safety. Precise cell modulation demands multi-modal display of functional proteins with controlled densities on biomaterials. Here, we develop an artificial immune cell engager (AICE) platform - biodegradable particles onto which multiple proteins are densely loaded with ratiometric control via short nucleic acid tethers. We demonstrate the impact of AICE with varying ratios of anti-CD3 and anti-CD28 antibodies on ex vivo expansion of human primary T cells. We also show that AICE can be used to control the activity of engineered T cells in vivo. AICE injected intratumorally can provide a local priming signal for systemically administered AND-gate chimeric antigen receptor T cells, driving local tumor clearance while sparing uninjected tumors that model potentially cross-reactive healthy tissues. This modularly functionalized biomaterial thus provides a flexible platform to achieve sophisticated control over cell-based immunotherapies.",2019-03-23,"Huang, X.; Williams, J. Z.; Chang, R.; Li, Z.; Gai, E.; Patterson, D. M.; Yu, W.; Lim, W. A.; Desai, T. A.",,,,True
f93daa3d8d53761cfcf4c9fb8ff03dace02a858c,biorxiv,Inhibition of arterivirus RNA synthesis by cyclophilin inhibitors is counteracted by mutations in replicase transmembrane subunits,doi.org/10.1101/587261,,,See https://www.biorxiv.org/about-biorxiv,"Previously, the cyclophilin inhibitors cyclosporin A (CsA) and Alisporivir (ALV) were shown to inhibit the replication of diverse RNA viruses, including arteriviruses and coronaviruses, which both belong to the order Nidovirales. Here we aimed to identify arterivirus proteins involved in the mode-of-action of cyclophilin inhibitors and to investigate how these compounds inhibit arterivirus RNA synthesis in the infected cell. Repeated passaging of the arterivirus prototype equine arteritis virus (EAV) in the presence of CsA revealed that reduced drug sensitivity is associated with the emergence of adaptive mutations in nonstructural protein 5 (nsp5), one of the transmembrane subunits of the arterivirus replicase polyprotein. Introduction of singular nsp5 mutations (nsp5 Q21R, Y113H, or A134V) led to a [~]2-fold decrease in sensitivity to CsA treatment, whereas combinations of mutations further increased EAVs CsA resistance. The detailed experimental characterization of engineered EAV mutants harboring CsA-resistance mutations implicated nsp5 in arterivirus RNA synthesis. Particularly, in an in vitro assay, EAV RNA synthesis was far less sensitive to CsA treatment when nsp5 contained the adaptive mutations mentioned above. Interestingly, for increased sensitivity to the closely-related drug ALV CsA-resistant nsp5 mutants required the incorporation of an additional adaptive mutation, which resided in nsp2 (H114R), another transmembrane subunit of the arterivirus replicase. Our study provides the first evidence for the involvement of nsp2 and nsp5 in the mechanism underlying the inhibition of arterivirus replication by cyclophilin inhibitors.\n\nImportanceCurrently, no approved treatments are available to combat infections with nidoviruses, a group of plus-stranded RNA viruses including important zoonotic and veterinary pathogens. Previously, the cyclophilin inhibitors cyclosporin A (CsA) and Alisporivir (ALV) were shown to inhibit the replication of diverse nidoviruses (both arteriviruses and coronaviruses), and may thus represent a class of pan-nidovirus inhibitors. Here, using the arterivirus prototype equine arteritis virus, we have established that resistance to CsA and ALV treatment is associated with adaptive mutations in two trans-membrane subunits of the viral replication complex, nonstructural proteins 2 and 5. This is the first evidence for the involvement of specific replicase subunits of nidoviruses in the mechanism underlying the inhibition of their replication by cyclophilin inhibitors. Understanding this mechanism of action is of major importance to guide future drug design, both for nidoviruses and other RNA viruses inhibited by these compounds.",2019-03-24,"De Wilde, A. H.; Boomaars-van der Zanden, L.; de Jong, A. W. M.; Barcena, M.; Snijder, E. J.; Posthuma, C. C.",,,,True
526c800695643e303ad5671d00693dd0f9b84eb0,biorxiv,tailfindr: Alignment-free poly(A) length measurement for Oxford Nanopore RNA and DNA sequencing,doi.org/10.1101/588343,,,See https://www.biorxiv.org/about-biorxiv,"Polyadenylation at the 3-end is a major regulator of messenger RNA and its length is known to affect nuclear export, stability and translation, among others. Only recently, strategies have emerged that allow for genome-wide poly(A) length assessment. These methods identify genes connected to poly(A) tail measurements indirectly by short-read alignment to genetic 3-ends. Concurrently Oxford Nanopore Technologies (ONT) established full-length isoform RNA sequencing containing the entire poly(A) tail. However, assessing poly(A) length through basecalling has so far not been possible due the inability to resolve long homopolymeric stretches in ONT sequencing.\n\nHere we present tailfindr, an R package to estimate poly(A) tail length on ONT long-read sequencing data. tailfindr operates on unaligned, basecalled data. It measures poly(A) tail length from both native RNA and DNA sequencing, which makes poly(A) tail studies by full-length cDNA approaches possible for the first time. We assess tailfindrs performance across different poly(A) lengths, demonstrating that tailfindr is a versatile tool providing poly(A) tail estimates across a wide range of sequencing conditions.",2019-03-26,"Krause, M.; Niazi, A. M.; Labun, K.; Müller, F. S.; Torres Cleuren, Y. N.; Valen, E.",,,,True
d4e1b8705646c89433773a9f67bdb8c12fcf4cef,biorxiv,EPS8 facilitates uncoating of influenza A virus,doi.org/10.1101/592485,,,See https://www.biorxiv.org/about-biorxiv,"All viruses balance interactions between cellular machinery co-opted to support replication and host factors deployed to halt the infection. We used gene correlation analysis to perform an unbiased screen for host factors involved in influenza A virus (FLUAV) infection. Our screen identified the cellular factor epidermal growth factor receptor pathway substrate 8 (EPS8) as the highest confidence pro-viral candidate. Knockout and overexpression of EPS8 confirmed its importance in enhancing FLUAV infection and titers. Loss of EPS8 did not affect virion attachment, uptake, or fusion. Rather, our data show that EPS8 specifically functions during virion uncoating. EPS8 physically associated with incoming virion components, and subsequent nuclear import of released ribonucleoprotein complexes was significantly delayed in the absence of EPS8. Our study identified EPS8 as a host factor important for uncoating, a crucial step of FLUAV infection during which the interface between the virus and host is still being discovered.",2019-03-28,"Larson, G. P.; Tran, V.; Yu, S.; Cai, Y.; Higgins, C. A.; Smith, D. M.; Baker, S. F.; Radoshitzky, S. R.; Kuhn, J. H.; Mehle, A.",,,,True
a2ba0a34df31fd8059ed22787331a75b65eafa74,biorxiv,Real-time projections of epidemic transmission and estimation of vaccination impact during an Ebola virus disease outbreak in Northeastern Democratic Republic of Congo,doi.org/10.1101/461285,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundAs of October 12, 2018, 211 cases of Ebola virus disease (EVD) were reported in North Kivu Province, Democratic Republic of Congo. Since the beginning of October the outbreak has largely shifted into regions in which active armed conflict is occurring, and in which EVD cases and their contacts are difficult for health workers to reach. We used available data on the current outbreak with case-count time series from prior outbreaks to project the short-term and long-term course of the outbreak.\n\nMethodsFor short and long term projections we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used a negative binomial autoregression for short-term projections, a Theil-Sen regression model for final sizes, and a baseline minimum-information projection using Gotts law to construct an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20 to October 13, short-term model projections were validated against actual case counts.\n\nResultsDuring validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of October 13, the stochastic model projected a median case count of 226 cases by October 27 (95% prediction interval: 205-268) and 245 cases by November 10 (95% prediction interval: 208-315), while the auto-regression model projects median case counts of 240 (95% prediction interval: 215-307) and 259 (95% prediction interval: 216-395) cases for those dates, respectively. Projected median final counts range from 274 to 421. Except for Gotts law, the projected probability of an outbreak comparable to 2013-2016 is exceedingly small. The stochastic model estimates that vaccine coverage in this outbreak is lower than reported in its trial setting in Sierra Leone.\n\nConclusionsBased on our projections we believe that the epidemic had not yet peaked at the time of these estimates, though a trajectory on the scale of the West African outbreak is exceedingly improbable. Validating our models in real time allowed us to generate more accurate short-term forecasts, and this process may provide a useful roadmap for real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges.",2019-03-28,"Worden, L.; Wannier, R.; Hoff, N. A.; Musene, K.; Selo, B.; Mossoko, M.; Okitolonda-Wemakoy, E.; Muyembe-Tamfum, J. J.; Rutherford, G. W.; Lietman, T. M.; Rimoin, A. W.; Porco, T. C.; Kelly, J. D.",,,,True
541777e512aa3907a9db91cde5207a07eabde5ef,biorxiv,Lipidome profiles of postnatal day 2 vaginal swabs reflect fat composition of gilts postnatal diet,doi.org/10.1101/593392,,,See https://www.biorxiv.org/about-biorxiv,"We hypothesized that postnatal development of the vagina is impacted by early nutritional environment. Our objective was to determine if lipid profiles of vaginal swabs were different between gilts suckled by sow or fed milk replacer the first 48 h postpartum, with and without a lard-based fat supplement. Gilts (>1.3 kg) were selected at birth across 8 litters and assigned to treatments: colostrum suckled (S, n=8); S plus fat supplement (SF, n=5); bottle-fed milk replacer (B, n=8); or B plus fat supplement (BF, n=7). At 48 h postnatal, vaginal swabs were taken with a cytology brush, immersed in ultrapure water to burst cells, and lipids extracted for analysis using multiple reaction monitoring (MRM)-profiling. Lipids extracted from serum collected at 48 h from gilts and milk collected from sows at 24 h were also analyzed with MRM-profiling. Receiver operating characteristic curve analysis found 18 lipids highly distinguished [area-under-the-curve (AUC) > 0.9] between S and B gilts, including phosphatidylethanolamine with 34 carbon and four unsaturations in the fatty acyl residues [PE(34:4)]. Twelve lipids from vaginal swabs highly correlated (r > 0.6; p < 0.01) with nutrition source. Lipids more abundant in milk replacer drove association. For example, mean intensity of PE (34:4) was 149-fold higher in milk replacer than colostrum, with 1.6- and 2.12-fold higher levels in serum and vaginal swab samples (p < 0.001), respectively, of B versus S gilts. Findings support that vaginal swabs can be used to noninvasively study effects of perinatal nutrition on tissue composition.\n\nSummary sentenceVaginal swab lipidome profiles at 48 h reflect the fat composition of neonatal diet during first two days postnatal.",2019-03-29,"Harlow, K.; Ferreira, C. R.; Sobreira, T. J. P.; Casey, T. M.; Stewart, K.",,,,True
c986b86bdcfe67f58b252361d1c19782db69ce27,biorxiv,A Novel Method for the Capture-based Purification of Whole Viral Native RNA Genomes,doi.org/10.1101/410282,,,See https://www.biorxiv.org/about-biorxiv,"Current technologies for targeted characterization and manipulation of viral RNA either involve amplification or ultracentrifugation with isopycnic gradients of viral particles to decrease host RNA background. The former strategy is non-compatible for characterizing properties innate to RNA strands such as secondary structure, RNA-RNA interactions, and also for nanopore direct RNA sequencing involving the sequencing of native RNA strands. The latter strategy, ultracentrifugation, causes loss in genomic information due to its inability to retrieve unassembled viral RNA. We developed a novel nucleic acid manipulation technique involving the capture of whole viral native RNA genomes for downstream RNA assays using hybridization baits in solution to circumvent these problems. This technique involves hybridization of biotinylated baits at 500 nucleotides (nt) intervals, stringent washes and release of free native RNA strands using DNase I treatment, with a turnaround time of about 6 h 15 min. Proof of concept was primarily done using RT-qPCR with dengue virus infected Huh-7 cells. We report that this protocol was able to purify viral RNA (561-791 fold). We also describe a successful application of our capture-based purification method to direct RNA sequencing, with a 77.47% of reads mapping to the target viral genome. We observed a reduction in human host RNA background by 1580 fold, a 99.91% recovery of viral genome with at least 15x coverage, and a mean coverage across the genome of 120x. This report is, to the best of our knowledge, the first description of a capture-based purification method for whole viral RNA genomes. The fundamental advantages of using our capture-based purification method makes it a superior alternative to conventional viral purification methods and would potentially pave a new path for the direct characterization and sequencing of native RNA molecules.",2019-04-01,"Tan, C. C. S.; Maurer-Stroh, S.; Wan, Y.; Sessions, O. M.; de Sessions, P. F.",,,,False
2d02192c3d251c2b561d37274350660277658a74,biorxiv,Enabling large-scale genome editing by reducing DNA nicking,doi.org/10.1101/574020,,,See https://www.biorxiv.org/about-biorxiv,"To extend the frontier of genome editing and enable the radical redesign of mammalian genomes, we developed a set of dead-Cas9 base editor (dBE) variants that allow editing at tens of thousands of loci per cell by overcoming the cell death associated with DNA double-strand breaks (DSBs) and single-strand breaks (SSBs). We used a set of gRNAs targeting repetitive elements - ranging in target copy number from about 31 to 124,000 per cell. dBEs enabled survival after large-scale base editing, allowing targeted mutations at up to ~13,200 and ~2610 loci in 293T and human induced pluripotent stem cells (hiPSCs), respectively, three orders of magnitude greater than previously recorded. These dBEs can overcome current on-target mutation and toxicity barriers that prevent cell survival after large-scale genome engineering.\n\nOne Sentence SummaryBase editing with reduced DNA nicking allows for the simultaneous editing of >10,000 loci in human cells.",2019-04-04,"Smith, C. J.; Castanon, O.; Said, K.; Volf, V.; Khoshakhlagh, P.; Hornick, A.; Ferreira, R.; Wu, C.-T.; Güell, M.; Garg, S.; Myllykallio, H.; Church, G. M.",,,,True
aacc3acdd6a928fd820d51a2d1ea98c164b6abd4,biorxiv,Congruence of location-specific transcriptional programs in intestinal organoids during long-term culture,doi.org/10.1101/600940,,,See https://www.biorxiv.org/about-biorxiv,"The emergence of intestinal organoids, as a stem cell-based self-renewable model system, has led to many studies on intestinal development and cell-cell signaling. However, potential issues regarding the phenotypic stability and reproducibility of the methodology during culture still needs to be addressed for different organoids. Here we investigated the transcriptomes of intestinal organoids derived from the same pig as well as batch-to-batch variation of organoids derived from different pigs over long-term passage. The set of genes expressed in organoids closely resembled that of the tissue of origin, including location specific functions, for at least 17 passages. Minor differences in gene expression were observed between individual organoid cultures. In contrast, most tissue-specific genes were not expressed in the transformed jejunum cell line IPECJ2, which also showed gene expression consistent with cancer phenotypes. We conclude that intestinal organoids provide a robust and stable model for translational research with clear advantages over transformed cells.",2019-04-05,"van der Hee, B.; Madsen, O.; Smidt, H.; Wells, J. M.",,,,True
d92e6ddc127c4dd588cfa8fd584a9a1adb4bbe86,biorxiv,Identification of viruses with the potential to infect human,doi.org/10.1101/597963,,,See https://www.biorxiv.org/about-biorxiv,"The virus has caused much mortality and morbidity to humans, and still posed a serious threat to the global public health. The virome with the human-infection potential is far from complete. Novel viruses have been discovered at an unprecedented pace as the rapid development of viral metagenomics. However, there is still a lack of a method for rapidly identifying the virus with the human-infection potential. This study built several machine learning models for discriminating the human-infecting viruses from other viruses based on the frequency of k-mers in the viral genomic sequences. The k-nearest neighbor (KNN) model could predict the human-infecting virus with an accuracy of over 90%. Even for the KNN models built on the contigs as short as 1kb, they performed comparably to those built on the viral genomes, suggesting that the models could be used to identify the human-infecting virus from the viral metagenomic sequences. This work could help for discovery of novel human-infecting virus in metagenomics studies.",2019-04-05,"Zhang, Z.; Cai, Z.; Tan, Z.; Lu, C.; Jiang, T.; Zhang, G.; Peng, Y.",,,,True
84c3cb4cff4551bf95b6f79bd6c52525faee0a44,biorxiv,Prediction of antiviral drugs against African Swine Fever Viruses based on protein-protein interaction analysis,doi.org/10.1101/599043,,,See https://www.biorxiv.org/about-biorxiv,"The African swine fever virus (ASFV) has severely influenced the swine industry of the world. Unfortunately, there is no effective antiviral drug or vaccine against the virus until now. Identification of new anti-ASFV drugs is urgently needed. Here, an up-to-date set of protein-protein interactions (PPIs) between ASFV and swine were curated by integration of PPIs from multiple sources. Thirty-two swine proteins were observed to interact with ASFVs and were defined as AIPs. They were found to play a central role in the swine PPI network, with significant larger degree, betweenness and smaller shortest path length than other swine proteins. Some of AIPs also interacted with several other viruses and could be taken as potential targets of drugs for broad-spectrum effect, such as HSP90AB1. Finally, the antiviral drugs which targeted AIPs and ASFV proteins were predicted. Several drugs with either broad-spectrum effect or high specificity on AIPs were identified, such as Polaprezinc. This work could not only deepen our understanding towards the ASFV-swine interactions, but also help for the development of effective antiviral drugs against the ASFVs.",2019-04-05,"zhu, z.; Fan, Y.; Cai, Z.; Zhang, Z.; Lu, C.; Zhang, G.; Jiang, T.; Peng, Y.",,,,True
a83b9f98ccbd6dd76d47c49cfe5785f9c2ecc09e,biorxiv,Large-scale Lassa fever outbreaks in Nigeria: quantifying the association between disease reproduction number and local rainfall,doi.org/10.1101/602706,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundLassa fever (LF) is increasingly recognized as an important rodent-borne viral hemorrhagic fever presenting a severe public health threat to sub-Saharan West Africa. In 2018, LF caused an unprecedented outbreak in Nigeria, and the situation was worse in 2019. This work aims to study the epidemiological features of outbreaks in different Nigerian regions and quantify the association between reproduction number (R) and local rainfall by using modeling analysis.\n\nMethodsWe quantify the infectivity of LF by the reproduction numbers estimated from four different growth models: the Richards, three-parameter logistic, Gompertz, and Weibull growth models. LF surveillance data are used to fit the growth models and estimate the Rs and epidemic turning points ({tau}) in different regions at different time periods. Cochrans Q test is further applied to test the spatial heterogeneity of the LF epidemics. A linear random-effect regression model is adopted to quantify the association between R and local rainfall with various lag terms.\n\nFindingsOur estimated Rs for 2017-18 (1.33 with 95% CI: [1.29, 1.37]) and 2018-19 (1.29 with 95% CI: [1.27, 1.32]) are significantly higher than those for 2016-17 (1.23 with 95% CI: [1.22, 1.24]). We report spatial heterogeneity in the Rs for outbreaks in different Nigerian regions. For the association between rainfall and R, we find that a one unit (mm) increase in average rainfall over the past 7 months could cause a 0.62% (95% CI: [0.20%, 1.05%]) rise in R.\n\nConclusionThere is significant spatial heterogeneity in the LF epidemics in different Nigerian regions. We report clear evidence of rainfall impacts on LF outbreaks in Nigeria and quantify the impact.",2019-04-08,"ZHAO, S. F.; MUSA, S. S.; Fu, H.; He, D.; Qin, J.",,,,True
874eaaeda2e803101ab952b3d9bc73426111b3d4,biorxiv,The Israeli Acute Paralysis Virus IRES captures host ribosomes by mimicking a ribosomal state with hybrid tRNAs.,doi.org/10.1101/606236,,,See https://www.biorxiv.org/about-biorxiv,"The Colony Collapse Disorder or CCD is a multi-faceted syndrome decimating bee populations worldwide[1]. A group of viruses of the widely distributed Dicistroviridae family have been identified as a causing agent of CCD[2]. This family of viruses employ non-coding RNA sequences, called Internal Ribosomal Entry Site (IRES), to precisely exploit the host machinery for protein production. Using single-particle cryo-electron microscopy (cryo-EM) we have characterized at high resolution how the IRES of the intergenic region of the Israeli Acute Paralysis Virus (IAPV) captures and redirects translating ribosomes towards viral messengers. Through a series of six structures at nominal resolutions close to 3[A], we could reconstruct the trajectory of IAPV-IRES from an early small subunit recruitment to a final post-translocated state in the ribosome. An early commitment of IRES/ribosome complexes for global pre-translocation mimicry explains the high efficiency observed for this IRES. The presented structures will help guide on-going efforts directed towards fighting CCD through RNA-interference technology [3].",2019-04-11,"Fernandez, I.; Frank, J.; Acosta-Reyes, F.; Neupane, R.",,,,True
3a81dbb6350d25798f401c332abcf1b49616ffef,biorxiv,More than efficacy revealed by single-cell analysis of antiviral therapeutics,doi.org/10.1101/606715,,,See https://www.biorxiv.org/about-biorxiv,"Development of antiviral therapeutics emphasizes minimization of the effective dose and maximization of the toxic dose, first in cell culture and later in animal models. Long-term success of an antiviral therapeutic is determined not only by its efficacy but also by the duration of time required for drug-resistance to evolve. We have developed a microfluidic device comprised of ~6000 wells, with each well containing a microstructure to capture single cells. We have used this device to characterize enterovirus inhibitors with distinct mechanisms of action. In contrast to population methods, single-cell analysis reveals that each class of inhibitor interferes with the viral infection cycle in a manner that can be distinguished by principal component analysis. Single-cell analysis of antiviral candidates reveals not only efficacy but also properties of the members of the viral population most sensitive to the drug, the stage of the lifecycle most affected by the drug, and perhaps even if the drug targets an interaction of the virus with its host.",2019-04-12,"Liu, W.; Caglar, M.; Mao, Z.; Woodman, A.; Arnold, J.; Wilke, C.; Cameron, C. E.",,,,True
63b645b7d8cd2502bedca374d0418486838bf4a0,biorxiv,Correlation of mRNA delivery timing and protein expression in lipid-based transfection,doi.org/10.1101/607986,,,See https://www.biorxiv.org/about-biorxiv,"Non-viral gene delivery is constrained by the dwell time that most synthetic nucleic acid nanocarriers spend inside endosomal compartments. In order to overcome this endosomal-release bottleneck, methods are required that measure nanocarrier uptake kinetics and transfection efficiency simultaneously. Here, we employ live-cell imaging on single-cell arrays (LISCA) to study the delivery-time distribution of lipid-based mRNA complexes under varied serum conditions. By fitting a translation-maturation model to hundreds of individual eGFP reporter fluorescence time courses, the protein expression onset times and the expression rates after transfection are determined. Using this approach, we find that delivery timing and protein expression rates are not intrinsically correlated at the single-cell level, even though population-averaged values of both parameters conjointly change as a function of increasing external serum protein fraction. Lipofectamine mediated delivery showed decreased transfection efficiency and longer delivery times with increasing serum protein concentration. This is in contrast to ionizable lipid nanoparticles (LNPs) mediated transfer, which showed increased efficiency and faster uptake in the presence of serum. In conclusion, the interdependences of single-cell expression rates and onset timing provide additional clues on uptake and release mechanisms, which are useful for improving nucleic acid delivery.",2019-04-13,"Reiser, A.; Woschee, D.; Mehrotra, N.; Krzyszton, R.; Strey, H. H.; Raedler, J. O.",,,,True
7e6bd4f9d794f87445f67c9ed9d5699706040fa4,biorxiv,Comparative analysis of gene expression in virulent and attenuated strains of infectious bronchitis virus at sub-codon resolution,doi.org/10.1101/612614,,,See https://www.biorxiv.org/about-biorxiv,"Infectious bronchitis virus (IBV) is a member of the genus Gammacoronavirus and the causative agent of avian infectious bronchitis. IBV has a single-stranded, positive-sense RNA genome ~27 kb in length and, like all coronaviruses, produces a set of sub-genomic messenger RNAs (sgmRNAs) synthesised via the viral polymerase. Here, we used RNA sequencing (RNASeq) and ribosome profiling (RiboSeq) to delineate gene expression in the IBV M41-CK and Beau-CK strains at sub-codon resolution. Quantification of reads flanking the programmed ribosomal frameshifting (PRF) signal at the genomic RNA ORF1a/ORF1b junction revealed that PRF in IBV is highly efficient (33-40%), consistent with in vitro measurements. Triplet phasing of the profiling data allowed precise determination of reading frames and revealed the translation of two intergenic genes (4b and 4c on sgmRNA4), which are widely conserved across IBV isolates. RNASeq revealed two novel transcription junction sites in the attenuated Beau-CK strain, one of which would generate a sgmRNA encoding a ribosomally occupied ORF in the viral 3 untranslated region (dORF). Within IBV transcripts, the nucleocapsid (N) protein was unexpectedly found to be inefficiently translated, despite being an abundant structural component of mature IBV virions. Finally, we demonstrate that the host cell response to IBV occurs primarily at the level of transcription, with a global up-regulation of immune-related mRNA transcripts following infection, and comparatively modest changes in the translation efficiencies of host genes.\n\nIMPORTANCEIBV is a major avian pathogen and presents a substantial economic burden to the poultry industry. Improved vaccination strategies are urgently needed to curb the global spread of this pathogen, and the development of suitable vaccine candidates will be aided by an improved understanding of IBV molecular biology. Our high-resolution data have enabled a precise study of transcription and translation in both pathogenic and attenuated forms of IBV, and expand our understanding of gammacoronaviral gene expression. We demonstrate that gene expression shows considerable intra-species variation, with single nucleotide polymorphisms associated with altered production of sgmRNA transcripts, and our RiboSeq data sets enabled us to uncover novel ribosomally occupied ORFs in both strains. We also identify numerous cellular genes and gene networks that are differentially expressed during virus infection, giving insights into the host cell reponse to IBV infection.",2019-04-18,"Dinan, A. M.; Keep, S.; Bickerton, E.; Britton, P.; Firth, A. E.; Brierley, I.",,,,True
1c06378f629bfa8870c89b3abfdecfc19db9b459,biorxiv,The Viral Protein Corona Directs Viral Pathogenesis and Amyloid Aggregation,doi.org/10.1101/246785,,,See https://www.biorxiv.org/about-biorxiv,"Artificial nanoparticles accumulate a protein corona layer in biological fluids, which significantly influences their bioactivity. As nanosized obligate intracellular parasites, viruses share many biophysical properties with artificial nanoparticles in extracellular environments and here we show that respiratory syncytial virus (RSV) and herpes simplex virus 1 (HSV-1) accumulate a rich and distinctive protein corona in different biological fluids. Moreover, we show that corona pre-coating differentially affects viral infectivity and immune cell activation. Additionally, we demonstrate that viruses bind amyloidogenic peptides in their corona and catalyze amyloid formation via surface-assisted heterogeneous nucleation. Importantly, we show that HSV-1 catalyzes the aggregation of the amyloid beta peptide (A{beta}42), a major constituent of amyloid plaques in Alzheimers disease, in-vitro and in animal models. Our results highlight the viral protein corona as an acquired structural layer that is critical for viral-host interactions and illustrate a mechanistic convergence between viral and amyloid pathologies.",2019-04-21,"Ezzat, K.; Pernemalm, M.; Palsson, S.; Roberts, T. C.; Jarver, P.; Dondalska, A.; Bestas, B.; Sobkowiak, M. J.; Levanen, B.; Skold, M.; Thompson, E. A.; Saher, O.; Kari, O. K.; Lajunen, T.; Sverremark Ekstrom, E.; Nilsson, C.; Ishchenko, Y.; Malm, T.; Wood, M. J. A.; Power, U. F.; Masich, S.; Linden, A.; Sandberg, J. K.; Lehtio, J.; Spetz, A.-L.; Andaloussi, S. E.",,,,True
d82fe700418fb6494ffb9a2c0cf4f6b8012b3824,biorxiv,Fitness barriers limit reversion of a proofreading-deficient coronavirus,doi.org/10.1101/618249,,,See https://www.biorxiv.org/about-biorxiv,"The 3'-to-5' exoribonuclease in coronavirus (CoV) nonstructural protein 14 (nsp14-ExoN) mediates RNA proofreading during genome replication. ExoN catalytic residues are arranged in three motifs: I (DE), II (E), III (D). Alanine substitution of the motif I residues (AA-E-D, four nucleotide substitutions) in murine hepatitis virus (MHV) and SARS-CoV yields viable mutants with impaired replication and fitness, increased mutation rates, and attenuated virulence in vivo. Despite these impairments, MHV- and SARS-CoV ExoN motif I AA mutants (ExoN-AA) have not reverted at motif I in diverse in vitro and in vivo environments, suggesting that profound fitness barriers prevent motif I reversion. To test this hypothesis, we engineered MHV-ExoN-AA with 1, 2 or 3 nucleotide mutations along genetic pathways to AA-to-DE reversion. We show that engineered intermediate revertants were viable but had no increased replication or competitive fitness compared to MHV-ExoN-AA. In contrast, a low passage (P10) MHV-ExoN-AA showed increased replication and competitive fitness without reversion of ExoN-AA. Finally, engineered reversion of ExoN-AA to ExoN-DE in the presence of ExoN-AA passage-adaptive mutations resulted in significant fitness loss. These results demonstrate that while reversion is possible, at least one alternative adaptive pathway is more rapidly advantageous than intermediate revertants and may alter the genetic background to render reversion detrimental to fitness. Our results provide an evolutionary rationale for lack of ExoN-AA reversion, illuminate potential multi-protein replicase interactions and coevolution, and support future studies aimed at stabilizing attenuated CoV ExoN-AA mutants.\n\nIMPORTANCECoronaviruses encode an exoribonuclease (ExoN) that is important for viral replication, fitness, and virulence, yet coronaviruses with a defective ExoN (ExoN-AA) have not reverted under diverse experimental conditions. In this study, we identify multiple impediments to MHV-ExoN-AA reversion. We show that ExoN-AA reversion is possible but evolutionarily unfavorable. Instead, compensatory mutations outside of ExoN-AA motif I are more accessible and beneficial than partial reversion. We also show that coevolution between replicase proteins over long-term passage partially compensates for ExoN-AA motif I but renders the virus inhospitable to a reverted ExoN. Our results reveal the evolutionary basis for the genetic stability of ExoN-inactivating mutations, illuminate complex functional and evolutionary relationships between coronavirus replicase proteins, and identify potential mechanisms for stabilization of ExoN-AA coronavirus mutants.",2019-04-26,"Graepel, K. W.; Agostini, M. L.; Lu, X.; Sexton, N. R.; Denison, M. R.",,,,True
d10525ee12ac8eb0941e0b21d04b3552baaeb79d,biorxiv,The guanine nucleotide exchange factor GBF1 participates in rotavirus replication,doi.org/10.1101/619924,,,See https://www.biorxiv.org/about-biorxiv,"Cellular and viral factors participate in the replication cycle of rotavirus. We report that the guanine nucleotide exchange factor GBF1, which activates the small GTPase Arf1 to induce COPI transport processes, is required for rotavirus replication since knocking down GBF1 expression by RNA interference, or inhibiting its activity by treatment with Brefeldin A (BFA) or Golgicide A (GCA) significantly reduce the yield of infectious viral progeny. This reduction in virus yield was related to a block in virus assembly since in the presence of either BFA or GCA the assembly of infectious mature triple-layered virions was significantly prevented and only doubled layered-particles were detected. We report that the catalytic activity of GBF1, but not the activation of Arf1, is essential for the assembly of the outer capsid of rotavirus. We show that both BFA and GCA, as well as interfering with the synthesis of GBF1, alter the electrophoretic mobility of glycoproteins VP7 and NSP4 and block the trimerization of the virus surface VP7, a step required for its incorporation into virus particles. Although a post-translational modification of VP7 (other than glycosylation) could be related to the lack of trimerization, we found that NSP4 might also be involved in this process, since knocking-down its expression reduces VP7 trimerizarion. In support, recombinant VP7 protein overexpressed in transfected cells formed trimers only when co-transfected with NSP4.\n\nIMPORTANCERotavirus, a member of the family Reoviridae, is the major cause of severe diarrhea in children and young animals worldwide. Despite the significant advances in the characterization of the biology of this virus, the mechanisms involved in morphogenesis of the virus particle are still poorly understood. In this work, we show that the guanine nucleotide exchange factor GBF1, relevant for the COPI/Arf1-mediated cellular vesicular transport, participates in the replication cycle of the virus, influencing the correct processing of viral glycoproteins VP7 and NSP4, and the assembly of the virus surface proteins VP7 and VP4.",2019-04-29,"Martinez, J. L.; Arnoldi, F.; Schraner, E. M.; Eichwald, C.; Silva-Ayala, D.; Lee, E.; Sztul, E.; Burrone, O. R.; Lopez, S.; Arias, C. F.",,,,True
4b5ba0d8c476c899a79cec7872f7d2287937a59d,biorxiv,Isolated occurrences of membrane perturbation by mechanosensing from weakly aggregating silver nanoparticles,doi.org/10.1101/623678,,,See https://www.biorxiv.org/about-biorxiv,"Silver nanoparticles (AgNPs) have wide-ranging applications, including as additives in consumer products and in medical diagnostics and therapy. Therefore understanding how AgNPs interact with biological systems is important for ascertaining any potential health risks due to the likelihood of high levels of human exposure. Besides any severe, acute effects, it is desirable to understand more subtle interactions that could lead to milder, chronic health impacts. Nanoparticles are small enough to be able to enter biological cells and interfere with their internal biochemistry. The initial contact between nanoparticle and cell is at the plasma membrane. To gain fundamental mechanistic insight into AgNP-membrane interactions, we investigate these phenomena in minimal model systems using a wide-range of biophysical approaches applied to lipid vesicles. We find a strong dependence on the medium composition, where colloidally stable AgNPs in a glucose buffer have negligible effect on the membrane. However, at a physiological salt concentrations, the AgNPs start to weakly aggregate and sporadic but significant membrane perturbation events are observed. Under these latter conditions, transient poration and structural remodelling of some vesicle membranes is observed. We observe that the fluidity of giant vesicle membranes universally decreases by an average of 16% across all vesicles. However, we observe a small population of vesicles display a significant change in mechanical properties with lower bending rigidity and higher membrane tension. Therefore we argue that the isolated occurrences of membrane perturbation by AgNPs are due to low probability mechanosensing events of AgNP aggregation at the membrane.\n\nGRAPHICAL ABSTRACT\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC=\""FIGDIR/small/623678v1_ufig1.gif\"" ALT=\""Figure 1\"">\nView larger version (54K):\norg.highwire.dtl.DTLVardef@196aa51org.highwire.dtl.DTLVardef@87c12borg.highwire.dtl.DTLVardef@9b2096org.highwire.dtl.DTLVardef@7877f6_HPS_FORMAT_FIGEXP  M_FIG C_FIG",2019-04-30,"Arribas Perez, M.; Moriones, O. H.; Bastus, N. G.; Puntes, V.; Nelson, A.; Beales, P. A.",,,,True
e7bdd52badd2d2ca8ce7bd838ca42d02ca3396ee,biorxiv,Lipocalin-2 is a Sensitive and Specific Marker of Bacterial Infection in Children,doi.org/10.1101/623819,,,See https://www.biorxiv.org/about-biorxiv,"IntroductionBacterial infection is the leading cause of death in children globally. Clinical algorithms to identify children who are likely to benefit from antimicrobial treatment remain suboptimal. Biomarkers that accurately identify serious bacterial infection (SBI) could improve diagnosis and clinical management. Lipocalin 2 (LCN2) and neutrophil collagenase (MMP-8) are neutrophil-derived biomarkers associated with bacterial infection.\n\nMethodsWe evaluated LCN2 and MMP-8 as candidate biomarkers in 40 healthy controls and 151 febrile children categorised confirmed SBI, probable SBI, or viral infection. The diagnostic performance of LCN2 and MMP-8 to predict SBI was estimated by the area under the receiver operating characteristic curve (AUROC) and compared to the performance of C-reactive protein (CRP).\n\nResultsPlasma LCN2 and MMP-8 concentration were predictive of SBI. The AUROC (95% CI) for LCN2, MMP8 and CRP to predict SBI was 0.88 (0.82-0.94); 0.80 (0.72-0.87) and 0.89 (0.84-0.94), respectively. The diagnostic performance of LCN2 in combination with CRP was significantly superior to either marker alone: AUROC 0.92 (95% CI: 0.88-0.96).\n\nConclusionLCN2 is a sensitive and specific predictor of SBI in children which could be used to improve clinical management and antimicrobial stewardship. LCN2 should be further evaluated in prospective clinical studies.",2019-04-30,"Herberg, J.; Huang, H.; Thezenas, M. L.; Janes, V.; Carter, M.; Gormley, S.; Hamilton, M. S.; Kessler, B.; Levin, M.; Casals-Pascual, C.",,,,True
618cd102ec5051a05ca5131e21961c964152f15c,biorxiv,Mating strategy is determinant of Adenovirus prevalence in European bats,doi.org/10.1101/626309,,,See https://www.biorxiv.org/about-biorxiv,"Adenoviruses are double-strained DNA viruses found in a great number of vertebrates, including humans. In order to understand their transmission dynamics, it is crucial, even from a human health perspective, to investigate how host traits influence their prevalence. Bats are important reservoirs for Adenoviruses, and here we use the results of recent screenings in Western Europe to evaluate the association between characteristic traits of bat species and their probability of hosting Adenoviruses, taking into account their phylogenetic relationships. Across species, we found an important phylogenetic component in the presence of Adenoviruses and mating strategy as the most determinant factor conditioning the prevalence of Adenoviruses across bat species. Contrary to other more stable mating strategies (e.g. harems), swarming could hinder transmission of Adenoviruses since this strategy implies that contacts between individuals are too short. Alternatively, bat species with more promiscuous behavior may develop a stronger immune system. Outstandingly high prevalence of Adenoviruses was reported for the Iberian species Pipistrellus pygmaeus, P. kuhlii and Nyctalus lasiopterus and we found that in the latter, males were more likely to be infected by Adenoviruses than females, due to the immunosuppressing consequence of testosterone during the mating season. As a general trend across species, we found that the number of Adenoviruses positive individuals was different across localities and that the difference in prevalence between populations was correlated with their geographic distances (P. pygmaeus). These results increase our knowledge about the transmission mechanisms of Adenoviruses.\n\nAuthor SummaryAdenoviruses are DNA viruses with a wide range of vertebrate hosts, including humans, causing ocular, respiratory and gastrointestinal diseases. Here, we focus on the prevalence of Adenoviruses in bats, which are known to be natural reservoir of many viruses, using the results of recent screenings for prevalence of these viruses in 33 European bat species. Our aim is to find association between Adenoviruses prevalence and biological and behavioral host traits, considering the heterogeneity both between and within species in order to have a deeper understanding of mechanisms of viral transmission.\n\nOur results highlight the importance of mating strategy: bats species using swarming as mating strategy are less likely to be infected by Adenoviruses. Moreover, we found that locality of capture can explain a higher prevalence of Adenovirus within species. However, no general pattern has been found in the analysis at individual level, suggesting a strong species specificity and complex viral transmission dynamics.",2019-05-02,"Rossetto, F.; Iglesias-Caballero, M.; Liedtke, C.; Gomez-Mestre, I.; Berciano, J. M.; Perez-Suarez, G.; de Paz, O.; Echevarria, J. E.; Casas, I.; Juste, J.",,,,True
f810de29894bfa40d93bc6dde3efc22c9d0d3f4c,biorxiv,Extensive genetic diversity of bat-borne polyomaviruses reveals inter-family host-switching events,doi.org/10.1101/627158,,,See https://www.biorxiv.org/about-biorxiv,"Polyomaviruses (PyVs) are small, double-stranded DNA tumor viruses carried by diverse vertebrates. PyVs have previously been considered highly host restricted in mammalian hosts, with host-switching events thought rare or nonexistent. Prior investigations have revealed short-range host-switching events of PyVs in two different African bat species within the horseshoe bat genus Rhinolophus. Herein, we have conducted a systematic investigation of PyVs in 1,083 archived bat samples collected from five provinces across China, and identified 192 PyVs from 186 bats from 15 host species within 6 families (Rhinolophidae, Vespertilionidae, Hipposideridae, Emballonuridae, Miniopteridae and Pteropodidae) representing 28 newly-described PyVs, indicative of extensive genetic diversity of bat PyVs. Surprisingly, two PyVs were identified in multiple bat species from different families, and another PyV clustered phylogenetically with PyVs carried by bats from a different host family, indicative of three inter-family PyV host-switching events. The time to most recent common ancestor (tMRCA) of the three events was estimated at 0.02-11.6 million years ago (MYA), which is inconsistent with the estimated tMRCA of their respective bat hosts (36.3-66.7 MYA), and is most parsimoniously explained by host-switching events. PyVs identified from geographically separated Chinese horseshoe bat species in the present study showed close genetic identities, and clustered with each other and with PyVs from African horseshoe bats, allowing assessment of the effects of positive selection in VP1 within the horseshoe bat family Rhinolophidae. Correlation analysis indicated that co-evolution with their hosts contributed much more to evolutionary divergence of PyV than geographic distance. In conclusion, our findings provide the first evidence of inter-family host-switching events of PyV in mammals and challenge the prevailing evolutionary paradigm for strict host restriction of mammalian PyVs.\n\nAuthor summarySince the discovery of murine polyomavirus in the 1950s, polyomaviruses (PyVs) have been considered both genetically stable and highly host-restricted in their mammalian hosts. In this study, we have identified multiple cases of host-switching events of PyVs by large scale surveillance in diverse bat species collected in China. These host-switching events occurred between bat families living in the same colony, indicating that a large population with frequent contacts between different bat species may represent an ecological niche facilitating PyV host-switching. The cases studied involved members of bats from several families, including horseshoe bats, which were previously found to harbor a number of highly virulent viruses to both humans and domestic animals. Our findings have provided evidence that even highly host-specific DNA viruses can transmit between bats of different species and indicate an increased propensity for spillover events involving horseshoe bats. We propose an evolutionary scheme for bat-borne PyVs in which intra-host divergence and host-switching has generated the diverse PyVs in present day bats. This scheme provides a useful model to study the evolution of PyVs in other hosts and, potentially, the modeling of bat zoonoses and the transmission of other DNA viruses in other mammals, including humans.",2019-05-03,"Tan, Z.; Gonzalez, G.; Sheng, J.; Wu, J.; Zhang, F.; Xu, L.; Zhang, P.; Zhu, A.; Qu, Y.; Tu, C.; Carr, M. J.; He, B.",,,,True
3c476baf5542bef88b8aad92bcca6786d1afa282,biorxiv,DEN-IM: Dengue Virus identification from shotgun and targeted metagenomics,doi.org/10.1101/628073,,,See https://www.biorxiv.org/about-biorxiv,"Dengue virus (DENV) represents a public health and economic burden in affected countries. The availability of genomic data is key to understand viral evolution and dynamics, supporting improved control strategies. Currently, the use of High Throughput Sequencing (HTS) technologies, which can be applied both directly to patient samples (shotgun metagenomics) and to PCR amplified viral sequences (targeted metagenomics), is the most informative approach to monitor the viral dissemination and genetic diversity.\n\nDespite many advantages, these technologies require bioinformatics expertise and appropriate infrastructure for the analysis and interpretation of the resulting data. In addition, the many software solutions available can hamper reproducibility and comparison of results.\n\nHere we present DEN-IM, a one-stop, user-friendly, containerised and reproducible workflow for the analysis of DENV sequencing data, both from shotgun and targeted metagenomics approaches. It is able to infer DENV coding sequence (CDS), identify serotype and genotype, and generate a phylogenetic tree. It can easily be run on any UNIX-like system, from local machines to high-performance computing clusters, performing a comprehensive analysis without the requirement of extensive bioinformatics expertise.\n\nUsing DEN-IM, we successfully analysed two DENV datasets. The first comprised 25 shotgun metagenomic sequencing samples of varying serotype and genotype, including a spiked sample containing the existing four serotypes. The second dataset consisted of 106 targeted metagenomics samples of DENV 3 genotype III where DEN-IM allowed detection of the intra-genotype diversity.\n\nThe DEN-IM workflow, parameters and execution configuration files, and documentation are freely available at https://github.com/B-UMMI/DEN-IM.",2019-05-06,"Mendes, C. I.; Lizarazo, E.; Machado, M. P.; Silva, D. N.; Tami, A.; Ramirez, M.; Couto, N.; Rossen, J. W. A.; Carrico, J. A.",,,,True
fa6c14304fc37470639d55f97f7903035d768bd2,biorxiv,Pseudomonas aeruginosa lectin LecB impairs keratinocyte fitness by abrogating growth factor signalling,doi.org/10.1101/629972,,,See https://www.biorxiv.org/about-biorxiv,"Lectins are glycan-binding proteins with no catalytic activity and ubiquitously expressed in nature. Numerous bacteria employ lectins to efficiently bind to epithelia, thus facilitating tissue colonisation. Wounded skin is one of the preferred niches for Pseudomonas aeruginosa, which has developed diverse strategies to impair tissue repair processes and promote infection.\n\nHere, we analyse the effect of the P. aeruginosa fucose-binding lectin LecB on human keratinocytes and demonstrate that it triggers events in the host, upon binding to fucosylated residues on cell membrane receptors, that extend beyond its role as an adhesion molecule. We found that LecB associates with several growth factor receptors and dampens their signalling pathways, leading to the arrest of cell cycle. Additionally, we describe a novel LecB-triggered mechanism to downregulate host cell receptors by showing that LecB leads to insulin-like growth factor receptor 1 internalisation, without receptor activation, and subsequent missorting towards intracellular endosomal compartments.\n\nOverall, these data highlight that LecB is a multitask virulence factor that, through subversion of several host pathways, has a profound impact on keratinocyte proliferation and survival.",2019-05-07,"Landi, A.; Mari, M.; Wolf, T.; Kleiser, S.; Gretzmeier, C.; Wilhelm, I.; Kiritsi, D.; Thuenauer, R.; Geiger, R.; Nystroem, A.; Reggiori, F.; Claudinon, J.; Roemer, W.",,,,True
e8b8e0f027881d2480d808b05d9281a7ff4e9b4d,biorxiv,Downregulation of hippocampal NR2A/2B subunits related to cognitive impairment in a pristane-induced lupus BALB/c mice,doi.org/10.1101/631879,,,See https://www.biorxiv.org/about-biorxiv,"Neuropsychiatric systemic lupus erythematosus (NPSLE) is a severe complication associated with the neurotoxic effects of circulating autoantibodies in the central nervous system (CNS) manifested frequently as a learning and memory deficit. Pristane-induced lupus in BALB/c female mice is an experimental model that resembles some clinical and immunological SLE pathogenesis associated with environmental factors. Nevertheless, there is no experimental evidence that relate pristane-induced lupus with cognitive dysfunction associated with autoantibodies production.\n\nObjectiveTo evaluate cognitive impairment related to memory deficits in a pristane-induced lupus BALB/c female mice related to mRNA expression levels of NR2A/2B hippocampal subunits in short and long-term memory task at 7 and 12 weeks after LPS exposition (7wLPS and 12wLPS) in a behavioral test with the employment of Barnes maze.\n\nMethodsFifty-four female BALB/c mice of 8-12 weeks old were included in 2 experimental groups: 7 and 12 weeks after lypopolissacharide (LPS) exposure and classified in subgroups (control, pristane and pristane+LPS). To determine cognitive dysfunction, mice were tested in a Barnes maze. Serum anti-Sm antibodies and relative expression of hippocampal NR2A/NR2B subunits were quantified.\n\nResultsPristane and pristane+LPS mice showed a prolonged escape latency at 7wLPS than at 12wLPS in short-term memory. Downregulation of hippocampal NR2A subunit was more evident than NR2B in pristane and pristane+LPS at 7wLPS and 12wLPS. The anti-Sm autoantibodies levels correlate with the relative expression of NR2A.\n\nConclusionDownregulation of hippocampal NR2A/2B subunits in the pristane-model of lupus in BALB/c mice may be related to anti-Sm autoantibodies production with the consequence of cognitive impairment in early stages of autoimmune disease.",2019-05-08,"Luciano-Jaramillo, J.; Sandoval-Garcia, F.; Vazquez-Del Mercado, M.; Gutierrez-Mercado, Y. K.; Navarro-Hernandez, R. E.; Martinez-Garcia, E. A.; Pizano-Martinez, O.; Corona-Meraz, F. I.; Banuelos-Pineda, J.; Floresvillar-Mosqueda, J. F.; Martin Marquez, B. T.",,,,True
b7f94d0b929301cc7a5d8f68a74d4f0270c74649,biorxiv,"Electroporated recombinant proteins as tools for in vivo functional complementation, imaging, and chemical biology",doi.org/10.1101/631358,,,See https://www.biorxiv.org/about-biorxiv,"Delivery of native or chemically modified recombinant proteins into mammalian cells shows promise for functional investigations and various technological applications, but concerns that sub-cellular localization and functional integrity of delivered proteins may be affected remain high. Here, we surveyed batch electroporation as a delivery tool for single polypeptides and multi-subunit protein assemblies of kinetochores, a spatially confined and well-studied subcellular structures. After electroporation in human cells, recombinant fluorescent Ndc80 and Mis12 multi-subunit complexes displayed native localization, physically interacted with endogenous binding partners, and functionally complemented depleted endogenous counterparts to promote mitotic checkpoint signaling and chromosome segregation. Farnesylation is required for kinetochore localization of the Dynein adaptor Spindly. In cells with chronically inhibited farnesyl transferase activity, in vitro farnesylation and electroporation reconstituted robust kinetochore localization of Spindly. Thus, electroporation is uniquely versatile for delivering synthetic and, as required, chemically modified functional mimics of endogenous proteins, and is therefore a promising tool for chemical and synthetic biology.",2019-05-08,"Alex, A.; Piano, V.; Polley, S.; Stuiver, M.; Voss, S.; Ciossani, G.; Overlack, K.; Voss, B.; Wohlgemuth, S.; Petrovic, A.; Wu, Y.-W.; Selenko, P.; Musacchio, A.; Maffini, S.",,,,True
4ce668fe6eee9f59ed5ad0dfc0e9787777acd3be,biorxiv,Anti-microbial immunity is impaired in COPD patients with frequent exacerbations,doi.org/10.1101/632372,,,See https://www.biorxiv.org/about-biorxiv,BackgroundPatients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) sub-group requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD.\n\nMethodsWe measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. Ex vivo immune responses to rhinovirus infection in differentiated bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators ([&ge;]2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups.\n\nResultsFrequent exacerbators had reduced sputum cell mRNA expression of the anti-viral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. RV-induction of interferon and ISGs ex vivo was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators also had reduced sputum levels of the anti-microbial peptide mannose-binding lectin (MBL)-2 with an associated increase in sputum bacterial loads at 2 weeks following virus-associated exacerbation onset. MBL-2 levels correlated negatively with bacterial loads during exacerbation.\n\nConclusionThese data implicate deficient airway innate immunity in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate antimicrobial immunity in the lung could be a viable strategy for prevention/treatment of frequent exacerbations.,2019-05-09,"Singanayagam, A.; Loo, S.-L.; Calderazzo, M.; Finney, L. J.; Trujillo-Torralbo, M.-B.; Bakhsoliani, E.; Girkin, J. L.; Veerati, P. C.; Pathinayake, P. S.; Nichol, K. S.; Reid, A. T.; Footitt, J.; Johnston, S. L.; Bartlett, N.; Mallia, P.",,,,True
849f3072bfea322a2ed927f39a1127b882c95159,biorxiv,Conditional silencing of H-2Db class I molecule expression on dendritic cells modulates the protective and pathogenic kinetics of virus-antigen specific CD8 T cell responses during Theiler’s Virus infection,doi.org/10.1101/632265,,,See https://www.biorxiv.org/about-biorxiv,"Theilers murine encephalomyelitis virus (TMEV) infection of the central nervous system is rapidly cleared in C57BL/6 mice by an anti-viral CD8 T cell response restricted by the MHC class I molecule, H-2Db. While the CD8 T cell response against neurotropic viruses is well characterized, the identity and function of the antigen presenting cell(s) involved in this process is(are) less well defined. To address this gap in knowledge, we developed a novel C57BL/6 H-2Db conditional knockout mouse that expresses an H-2Db transgene in which the transmembrane domain locus is flanked by LoxP sites. We crossed these H-2Db LoxP mice with MHC class I-deficient mice expressing Cre-recombinase under either the CD11c or LysM promoter in order to silence H-2Db restricted antigen presentation predominantly in dendritic cells or macrophages, respectively. Upon challenge with intracranial TMEV infection, we observe that CD11c+ APCs are critical for early priming of CD8 T cells against the immunodominant TMEV peptide VP2121-130 presented in the context of the H-2Db molecule. This stands in stark contrast to later time points post TMEV infection where CD11c+ APCs appear dispensable for the activation of antigen-specific T cells; the functionality of these late-arising antiviral CD8 T cells is reflected in the restoration of viral control at later time points. These late-arising CD8 T cells also retain their capacity to induce blood-brain barrier disruption. In contrast, when H-2Db restricted antigen presentation was selectively silenced in LysM+ APCs there was no overt impact on the priming of Db:VP2121-130 epitope-specific CD8 T cells, although a modest reduction in immune cell entry into the CNS was observed. This work establishes a model system which enables critical dissection of MHC class I restricted antigen presentation to T cells, revealing cell specific and temporal features involved in the generation of antiviral CD8 T cell responses. Employing this novel system, we established CD11c+ cells as a pivotal driver of acute, but not later-arising, antiviral CD8 T cell responses against the TMEV immunodominant epitope VP2121-130, with functional implications both for T cell-mediated viral control and immunopathology.",2019-05-09,"Tritz, Z. P.; Orozco, R. C.; Malo, C. S.; Yokanovich, L. T.; Ayasoufi, K.; Fain, C. E.; Khadka, R. H.; Settell, M. L.; Hansen, M. J.; Jin, F.; Johnson, A. J.",,,,False
5b9a15ad62b0e85fcb5012e7e08e5183b4da786b,biorxiv,A systematic review and evaluation of Zika virus forecasting and prediction research during a public health emergency of international concern,doi.org/10.1101/634832,,,See https://www.biorxiv.org/about-biorxiv,"INTRODUCTIONEpidemic forecasting and prediction tools have the potential to provide actionable information in the midst of emerging epidemics. While numerous predictive studies were published during the 2016-2017 Zika Virus (ZIKV) pandemic, it remains unknown how timely, reproducible and actionable the information produced by these studies was.\n\nMETHODSTo improve the functional use of mathematical modeling in support of future infectious disease outbreaks, we conducted a systematic review of all ZIKV prediction studies published during the recent ZIKV pandemic using the PRISMA guidelines. Using MEDLINE, EMBASE and grey literature review, we identified studies that forecasted, predicted or simulated ecological or epidemiological phenomenon related to the Zika pandemic that were published as of March 01, 2017. Eligible studies underwent evaluation of objectives, data sources, methods, timeliness, reproducibility, accessibility and clarity by independent reviewers.\n\nRESULTS2034 studies were identified, of which n = 73 met eligibility criteria. Spatial spread, R0 (basic reproductive number) and epidemic dynamics were most commonly predicted, with few studies predicting Guillain-Barre Syndrome burden (4%), sexual transmission risk (4%) and intervention impact (4%). Most studies specifically examined populations in the Americas (52%), with few African-specific studies (4%). Case count (67%), vector (41%) and demographic data (37%) were the most common data sources. Real-time internet data and pathogen genomic information were used in 7% and 0% of studies, respectively, and social science and behavioral data were typically absent in modeling efforts. Deterministic models were favored over stochastic approaches. Forty percent of studies made model data entirely available, 29% provided all relevant model code, 43% presented uncertainty in all predictions and 54% provided sufficient methodological detail allowing complete reproducibility. Fifty-one percent of predictions were published after the epidemic peak in the Americas. While the use of preprints improved the accessibility of ZIKV predictions by a median 119 days sooner than journal publication dates, they were used in only 30% of studies.\n\nCONCLUSIONSMany ZIKV predictions were published during the 2016-2017 pandemic. The accessibility, reproducibility, timeliness, and incorporation of uncertainty in these published predictions varied and indicates that there is substantial room for improvement. To enhance the utility of analytical tools for outbreak response, it is essential to improve the sharing of model data, code, and preprints for future outbreaks, epidemics and pandemics.\n\nAuthor summaryResearchers published many studies which sought to predict and forecast important features of Zika virus (ZIKV) infections and their spread during the 2016-2017 ZIKV pandemic. We conducted a comprehensive review of such ZIKV prediction studies and evaluated their aims, the data sources they used, which methods were used, how timely they were published, and whether they provided sufficient information to be used or reproduced by others. Of the 73 studies evaluated, we found that the accessibility, reproducibility, timeliness, and incorporation of uncertainty in these published predictions varied and indicates that there is substantial room for improvement. We identified that the release of study findings before formal journal publication ( pre-prints) increased the timeliness of Zika prediction studies, but note they were infrequently used during this public health emergency. Addressing these areas can improve our understanding of Zika and other outbreaks and ensure that forecasts can inform preparedness and response to future outbreaks, epidemics and pandemics.",2019-05-10,"Kobres, P.-Y.; Chretien, J.-P.; Johansson, M. A.; Morgan, J.; Whung, P.-Y.; Mukundan, H.; Del Valle, S. Y.; Forshey, B. M.; Quandelacy, T. M.; Biggerstaff, M.; Viboud, C.; Pollett, S.",,,,True
00d16927588fb04d4be0e6b269fc02f0d3c2aa7b,biorxiv,"Real-time, MinION-based, amplicon sequencing for lineage typing of infectious bronchitis virus from upper respiratory samples",doi.org/10.1101/634600,,,See https://www.biorxiv.org/about-biorxiv,"Infectious bronchitis (IB) causes significant economic losses in the global poultry industry. Control of infectious bronchitis is hindered by the genetic diversity of the causative agent, infectious bronchitis virus (IBV), which has led to the emergence of several serotypes that lack complete serologic cross-protection. While serotyping by definition requires immunologic characterization, genotyping is an efficient means to identify IBVs detected in samples. Sanger sequencing of the S1 subunit of the spike gene is currently used to genotype IBV; however, the universal S1 PCR was created to work from cultured IBV and it is inefficient at detecting mixed isolates. This paper describes a MinION-based AmpSeq method that genetically typed IBV from clinical samples, including samples with multiple isolates. Total RNA was extracted from fifteen tracheal scrapings and choanal cleft swab samples, randomly reverse transcribed, and PCR amplified using modified S1-targeted primers. Amplicons were barcoded to allow for pooling of samples, processed per manufacturers instructions into a 1D MinION sequencing library, and sequenced on the MinION. The AmpSeq method detected IBV in 13 of 14 IBV-positive samples. AmpSeq accurately detected and genotyped both IBV lineages in three of five samples containing two IBV lineages. Additionally, one sample contained three IBV lineages, and AmpSeq accurately detected two of the three. Strain identification, including detection of different strains from the same lineage, was also possible with this AmpSeq method. The results demonstrate the feasibility of using MinION-based AmpSeq for rapid and accurate identification and lineage typing of IBV from oral swab samples.",2019-05-10,"Butt, S. L.; Erwood, E. C.; Zhang, J.; Sellers, H. S.; Young, K.; Lahmers, K. K.; Stanton, J. B.",,,,True
5a5a7b6d40c4b752aabf69f69bbd7c71e2658e8e,biorxiv,Tracking progress towards malaria elimination in China: estimates of reproduction numbers and their spatiotemporal variation,doi.org/10.1101/628842,,,See https://www.biorxiv.org/about-biorxiv,"China reported zero locally-acquired malaria cases in 2017 and 2018. Understanding the spatio-temporal pattern underlying this decline, especially the relationship between locally-acquired and imported cases, can inform efforts to maintain elimination and prevent re-emergence. This is particularly pertinent in Yunnan province, where the potential for local transmission is highest. Using a geo-located individual-level dataset of cases recorded in Yunnan province between 2011 and 2016, we jointly estimate the case reproduction number, Rc, and the number of unobserved sources of infection. We use these estimates within spatio-temporal geostatistical models to map how transmission varied over time and space, estimate the timeline to elimination and the risk of resurgence. Our estimates suggest that, maintaining current intervention efforts, Yunnan is unlikely to experience sustained local transmission up to 2020. However, even with a mean Rc of 0.005 projected for the year 2019, locally-acquired cases are possible due to high levels of importation.",2019-05-10,"Routledge, I.; Lai, S.; Battle, K. E.; Ghani, A. C.; Gomez Rodriguez, M.; Gustafson, K. B.; Mishra, S.; Proctor, J. L.; Tatem, A. J.; Li, Z.; Bhatt, S.",,,,True
f23d95687ec663dcbb51aab9841b5f23df9a1d2f,biorxiv,Peptidoglycan associated cyclic lipopeptide disrupts viral infectivity,doi.org/10.1101/635854,,,See https://www.biorxiv.org/about-biorxiv,"Enteric viruses exploit bacterial components including lipopolysaccharides (LPS) and peptidoglycan (PG) to facilitate infection in humans. With origins in the bat enteric system, we wondered if severe acute respiratory syndrome-coronavirus (SARS-CoV) or Middle East respiratory syndrome-CoV (MERS-CoV) also use bacterial components to modulate infectivity. To test this question, we incubated CoVs with LPS and PG and evaluated infectivity finding no change following LPS treatment. However, PG from B. subtilis reduced infection >10,000-fold while PG from other bacterial species failed to recapitulate this. Treatment with an alcohol solvent transferred inhibitory activity to the wash and mass spectrometry revealed surfactin, a cyclic lipopeptide antibiotic, as the inhibitory compound. This antibiotic had robust dose- and temperature-dependent inhibition of CoV infectivity. Mechanistic studies indicated that surfactin disrupts CoV virion integrity and surfactin treatment of the virus inoculum ablated infection in vivo. Finally, similar cyclic lipopeptides had no effect on CoV infectivity and the inhibitory effect of surfactin extended broadly to enveloped viruses including influenza, Ebola, Zika, Nipah, Chikungunya, Una, Mayaro, Dugbe, and Crimean-Congo hemorrhagic fever viruses. Overall, our results indicate that peptidoglycan-associated surfactin has broad virucidal activity and suggest bacteria byproducts may negatively modulate virus infection.\n\nImportanceIn this manuscript, we considered a role for bacteria in shaping coronavirus infection. Taking cues from studies of enteric viruses, we initially investigated how bacterial surface components might improve CoV infection. Instead, we found that peptidoglycan-associated surfactin is a potent viricidal compound that disrupts virion integrity with broad activity against enveloped viruses. Our results indicate that interactions with commensal bacterial may improve or disrupt viral infections highlighting the importance of understanding these microbial interactions and their implications for viral pathogenesis and treatment.",2019-05-13,"Johnson, B. A.; Hage, A.; Kalveram, B.; Mears, M.; Plante, J. A.; Rodriguez, S. E.; Ding, Z.; Luo, X.; Bente, D.; Bradrick, S. S.; Freiberg, A. N.; Popov, V.; Rajsbaum, R.; Rossi, S.; Russell, W. K.; Menachery, V. D.",,,,False
1dfcd4615a8763e053bd2fdb845f09fab68109f1,biorxiv,"Waterborne, abiotic and other indirectly transmitted (W.A.I.T.) infections are defined by the dynamics of free-living pathogens and environmental reservoirs",doi.org/10.1101/525089,,,See https://www.biorxiv.org/about-biorxiv,"While the ecology of infectious disease is a rich field with decades worth of empirical evidence and theory, there are aspects that remain relatively under-examined. One example is the importance of the free-living survival stage of certain pathogens, and especially is cases where they are transmitted indirectly between hosts through an environmental reservoir intermediate. In this study, we develop an integrated, broadly applicable mathematical method to examine diseases fitting this description--the waterborne, abiotic and other indirectly transmitted (W.A.I.T.) infection framework. To demonstrate its utility, we construct realistic models of two very different epidemic scenarios: cholera in a densely populated setting with limited access to clean drinking water and hepatitis C virus in an urban setting of injection-drug users. Using these two exemplars, we find that the W.A.I.T. model fortifies the centrality of reservoir dynamics in the ""sit and wait"" infection strategy, and provides a way to simulate a diverse set of intervention strategies.",2019-05-13,"Miller-Dickson, M.; Meszaros, V. A.; Baffour-Awuah Junior, F.; Almagro-Moreno, S.; Ogbunugafor, C. B.",,,,True
d29c253b473969c4d92ea9911d3badb9a7ee63f2,biorxiv,A nematode-specific gene underlies bleomycin-response variation in Caenorhabditis elegans,doi.org/10.1101/565218,,,See https://www.biorxiv.org/about-biorxiv,"Bleomycin is a powerful chemotherapeutic drug used to treat a variety of cancers. However, individual patients vary in their responses to bleomycin. The identification of genetic differences that underlie this response variation could improve treatment outcomes by tailoring bleomycin dosages to each patient. We used the model organism Caenorhabditis elegans to identify genetic determinants of bleomycin-response differences by performing linkage mapping on recombinants derived from a cross between the laboratory strain (N2) and a wild strain (CB4856). This approach identified a small genomic region on chromosome V that underlies bleomycin-response variation. Using near-isogenic lines and strains with CRISPR-Cas9 mediated deletions and allele replacements, we discovered that a novel nematode-specific gene (scb-1) is required for bleomycin resistance. Although the mechanism by which this gene causes variation in bleomycin responses is unknown, we suggest that a rare variant present in the CB4856 strain might cause differences in the potential stress-response function of scb-1 between the N2 and CB4856 strains, thereby leading to differences in bleomycin resistance.",2019-05-14,"Brady, S. C.; Zdraljevic, S.; Bisaga, K.; Tanny, R.; Cook, D. E.; Lee, D.; Wang, Y.; Andersen, E. C.",,,,True
6a8d26d75bd44c7666c9b7ed782c13a57f409122,biorxiv,Insufficiency in airway interferon activation defines clinical severity to infant RSV infection,doi.org/10.1101/641795,,,See https://www.biorxiv.org/about-biorxiv,"Respiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants. Other than age at the time of infection, the causes and correlates of severe illness in infants lacking known risk factors are poorly defined. We recruited a cohort of confirmed RSV-infected infants and simultaneously assayed the presence of resident airway microbiota and the molecular status of their airways using a novel method. Rigorous statistical analyses identified a molecular airway gene expression signature of severe illness dominated by excessive chemokine expression. Global 16S rRNA sequencing confirmed an association between H. influenzae and clinical severity. Interestingly, adjusting for H. influenzae in our gene expression analysis revealed an association between severity and airway lymphocyte accumulation. Exploring the relationship between airway gene expression and the time of onset of clinical symptoms revealed a robust, acute activation of interferon (IFN) signaling, which was absent in subjects with severe illness. Finally, we explored the relationship between IFN activity, airway gene expression and productive RSV infection using a novel in vitro model of bona fide pediatric human airway epithelial cells. Interestingly, blocking IFN signaling, but not IFN ligand production, in these cells leads to increased viral infection. Our data reveal that acute airway interferon responses are physiologically relevant in the context of infant RSV infection and may be a target for therapeutic intervention. Additionally, the airway gene expression signature we define may be useful as a biomarker for efficacy of intervention responses.",2019-05-20,"Chu, C.-Y.; Qiu, X.; McCall, M. N.; Wang, L.; Corbett, A.; Holden-Wiltse, J.; Slaunwhite, C.; Wang, Q.; Anderson, C.; Grier, A.; Gill, S. R.; Pryhuber, G. S.; Falsey, A. R.; Topham, D. J.; Caserta, M. T.; Walsh, E. E.; Mariani, T. J.",,,,True
0e2ba405f636e06821999876cd82c00e26404b43,biorxiv,Identification of a Nidovirales Orf1a N7-guanine cap methyltransferase signature-sequence as a genetic marker of large RNA genome Tobaniviridae,doi.org/10.1101/639369,,,See https://www.biorxiv.org/about-biorxiv,"Members of the Nidovirales order have (+)RNA genomes amongst the largest in size in the RNA virus world. Expression of their genes is promoted through reading of genomic RNA and mRNA transcripts by the ribosome of the infected cell. The 5-end of these RNAs is supposedly protected by an RNA-cap structure (m7GpppNm) whose most synthesis steps remain elusive. In Eukaryotes, the RNA-cap structure is methylated by RNA methyltransferases (MTases) at the RNA-cap N7-guanine position as well as the 2-O methyl position of the first transcribed nucleotide. In Coronaviridae, two separate enzymes (nsp14 and nsp16) perform the N7-guanine and the 2-OH methylation, respectively. One salient feature of the Nidovirales N7-guanine MTase nsp14 is that it is the only example of non-Rossman fold viral MTase known so far. Conversely, all other Nidovirales nsp16-like MTases have a canonical Rossman fold. Many Nidovirales members lack either any RNA MTase signature sequence (e.g., Arteriviridae), or lack a N7-guanine MTase signature sequence (e.g., Tobaniviridae, Euroniviridae, Roniviridae, Medioniviridae). Both nsp14-and nsp16-like enzyme genes are usually located in Orf1b encoding for the replication machinery. Here, we report the discovery of a putative Rossman fold RNA MTase in the Orf1a of ten Tobaniviridae members. Multiple sequence alignments and structural analyses identify this novel gene as a typical RNA-cap N7-guanine MTase with substrate specificity and active-site organization similar to the canonical eukaryotic RNA-cap N7-guanine MTase.",2019-05-23,"Ferron, F.; Debat, H.; Decroly, E.; Canard, B.",,,,True
1fb909712eea684a4fae4f0b419ca6bc7ba8e396,biorxiv,Modification of primary amines to higher order amines reduces in vivo hematological and immunotoxicity of cationic nanocarriers through TLR4 and complement pathways,doi.org/10.1101/647305,,,See https://www.biorxiv.org/about-biorxiv,"For decades, cationic polymer nanoparticles have been investigated for nucleic acid delivery. Despite promising in vitro transfection results, most formulations have failed to translate into the clinic due to significant in vivo toxicity - especially when delivered intravenously. To address this significant problem, we investigated the detailed mechanisms that govern the complex in vivo systemic toxicity response to common polymeric nanoparticles. We determined that the toxicity response is material dependent. For branched polyethylenimine (bPEI) nanoparticles - toxicity is a function of multiple pathophysiological responses - triggering of innate immune sensors, induction of hepatic toxicity, and significant alteration of hematological properties. In contrast, for chitosan-based nanoparticles - systemic toxicity is primarily driven through innate immune activation. We further identified that modification of primary amines to secondary and tertiary amines using the small molecule imidazole-acetic-acid (IAA) ameliorates in vivo toxicity from both nanocarriers by different, material-specific mechanisms related to Toll-like receptor 4 activation (for bPEI) and complement activation driven neutrophil infiltration (for chitosan), respectively. Our results provide a detailed roadmap for evaluating in vivo toxicity of nanocarriers and identifies potential opportunities to reduce toxicity for eventual clinical translation.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC=\""FIGDIR/small/647305v1_ufig1.gif\"" ALT=\""Figure 1\"">\nView larger version (27K):\norg.highwire.dtl.DTLVardef@63c7a7org.highwire.dtl.DTLVardef@c8ac52org.highwire.dtl.DTLVardef@a9589dorg.highwire.dtl.DTLVardef@1f8ec62_HPS_FORMAT_FIGEXP  M_FIG C_FIG",2019-05-24,"Toy, R.; Pradhan, P.; Ramesh, V.; Di Paolo, N. C.; Lash, B.; Liu, J.; Blanchard, E. L.; Santangelo, P. J.; Shayakhmetov, D. M.; Roy, K.",,,,True
13bf9fe0df944c0ee0debb0d445527ad4418cc19,biorxiv,"Expression of 9-O- and 7,9-O-acetyl modified sialic acids in cells and their effects on influenza viruses",doi.org/10.1101/650341,,,See https://www.biorxiv.org/about-biorxiv,"Sialic acids (Sia) are widely displayed on the surfaces of cells and tissues. Sia come in a variety of chemically modified forms, including those with acetyl modifications at the C7, C8, and C9 positions. Here, we analyzed the distribution and amounts of these acetyl modifications in different human and canine cells. As Sia or their variant forms are receptors for influenza A and influenza C viruses, we examined the effects of these modifications on virus infections. We confirmed that 9-O-acetyl and 7,9-O-acetyl modified Sia are widely but variably expressed across cell lines from both humans and canines. While they were expressed on the cell surface of canine MDCK cell lines, they were located primarily within the Golgi compartment of human HEK-293 and A549 cells. The O-acetyl modified Sia were expressed at low levels of 1-2% of total Sia in these cell lines. We knocked out and over-expressed the sialate O-acetyltransferase gene (CasD1), and knocked out the sialate O-acetylesterase gene (SIAE) using CRISPR/Cas9 editing. Knocking out CasD1 removed 7,9-O- and 9-O-acetyl Sia expression, confirming previous reports. However, over-expression of CasD1 and knockout of SIAE gave only modest increases in 9-O-acetyl levels in cells and no change in 7,9-O-acetyl levels, indicating that there are complex regulations of these modifications. These modifications were essential for influenza C infection, but had no obvious effect on influenza A infection.\n\nIMPORTANCESialic acids are key glycans that are involved in many different normal cellular functions, as well as being receptors for many pathogens. However, Sia come in diverse chemically modified forms. Here we examined and manipulated the expression of 7,9-O- and 9-O-acetyl modified Sia on cells commonly used in influenza virus and other research by engineering the enzymes that produce or remove the acetyl groups.",2019-05-25,"Barnard, K. N.; Wasik, B. R.; LaClair, J. R.; Weichert, W.; Lawrence, B. K.; Parrish, C. R.",,,,True
6d1b40bcdde63e22931509db389c6bf1949901dd,biorxiv,A combinatorial biomolecular strategy to identify peptides for improved transport across the sputum of cystic fibrosis patients and the underlying epithelia,doi.org/10.1101/659540,,,See https://www.biorxiv.org/about-biorxiv,"Drugs and drug delivery systems have to traverse multiple biological barriers to achieve therapeutic efficacy. In diseases of mucosal-associated tissues such as cystic fibrosis (CF), successful delivery of gene and drug therapies remains a significant challenge due to an abnormally concentrated viscoelastic mucus, which prevents ~99% of all drugs and particles from penetrating the mucus barrier and the underlying epithelia for effective therapy, resulting in decreased survival. We used combinatorial peptide-presenting phage libraries and next-generation sequencing to identify hydrophilic, close to net-neutral charged peptides that penetrate the mucus barrier ex vivo in sputum from CF patients with ~600-fold better penetration than a positively charged control. After mucus penetration, nanoparticles conjugated with our selected peptides successfully translocated into lung epithelial cells derived from CF patients and demonstrated up to three-fold improved cell uptake compared to non-modified carboxylated- and gold standard PEGylated-nanoparticles. The selected peptides act as surface chemistries with synergistic functions to significantly improve the ability of drug delivery systems to overcome the human mucosal barriers and provide efficient cellular internalization. Our screening strategy provides a biologically-based discovery assay that directly addresses transport through mucus and cell barriers and has the potential to advance drug and gene delivery to multiple mucosal barriers.",2019-06-04,"Leal, J.; Liu, X.; Peng, X.; Mohanty, R.; Arasappan, D.; Wylie, D. C.; Schwartz, S. H.; Fullmer, J. J.; McWilliams, B. C.; Smyth, H. D.; Ghosh, D.",,,,True
fcb76f0907f67a850fd4560218034f214fa28bcc,biorxiv,Identification of peptide coatings that enhance diffusive transport of nanoparticles through the tumor microenvironment,doi.org/10.1101/659524,,,See https://www.biorxiv.org/about-biorxiv,"In solid tumors, increasing drug penetration promotes their regression and improves the therapeutic index of compounds. However, the heterogeneous extracellular matrix (ECM) acts a steric and interaction barrier that hinders effective transport of therapeutics, including nanomedicines. Specifically, the interactions between the ECM and surface physicochemical properties of nanomedicines (e.g. charge, hydrophobicity) impedes their diffusion and penetration. To address the challenges using existing surface chemistries, we used peptide-presenting phage libraries as a high-throughput approach to screen and identify peptides as coatings with desired physicochemical properties that improve diffusive transport through the tumor microenvironment. Through iterative screening against the ECM and identification by next-generation DNA sequencing and analysis, we selected individual clones and measured their transport by diffusion assays. Here, we identified a net-neutral charge, hydrophilic peptide P4 that facilitates significantly higher diffusive transport of phage than negative control through in vitro tumor ECM. Through alanine mutagenesis, we confirmed that the hydrophilicity, charge, and their spatial ordering impact diffusive transport. P4 phage clone exhibited almost 200-fold improved uptake in ex vivo pancreatic tumor xenografts compared to the negative control. Nanoparticles coated with P4 exhibited [~]40-fold improvement in diffusivity in pancreatic tumor tissues, and P4-coated particles demonstrated less hindered diffusivity through the ECM compared to particles functionalized with gold standard poly(ethylene) glycol or iRGD peptide ligand. By leveraging the power of molecular diversity using phage display, we can greatly expand the chemical space of surface chemistries that can improve the transport of nanomedicines through the complex tumor microenvironment to ultimately improve their efficacy.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC=\""FIGDIR/small/659524v1_ufig1.gif\"" ALT=\""Figure 1\"">\nView larger version (23K):\norg.highwire.dtl.DTLVardef@18bc04forg.highwire.dtl.DTLVardef@1feb597org.highwire.dtl.DTLVardef@14403e5org.highwire.dtl.DTLVardef@5bbf6c_HPS_FORMAT_FIGEXP  M_FIG C_FIG",2019-06-04,"Mohanty, R.; Liu, X.; Kim, J. Y.; Peng, X.; Bhandari, S.; Leal, J.; Arasappan, D.; Wylie, D. C.; Dong, T.; Ghosh, D.",,,,True
03ce432f27c7df6af22b92245a614db2ecb5de5f,biorxiv,A hidden gene in astroviruses encodes a cell-permeabilizing protein involved in virus release,doi.org/10.1101/661579,,,See https://www.biorxiv.org/about-biorxiv,"Human astroviruses are small nonenveloped viruses with positive-sense single-stranded RNA genomes that contain three main open reading frames: ORF1a, ORF1b and ORF2. Astroviruses cause acute gastroenteritis in children worldwide and have been associated with encephalitis and meningitis in immunocompromised individuals. Through comparative genomic analysis of >400 astrovirus sequences, we identified a conserved \""ORFX\"" overlapping the capsid-encoding ORF2 in genogroup I, III and IV astroviruses. ORFX appears to be subject to purifying selection, consistent with it encoding a functional protein product, termed XP. Using ribosome profiling of cells infected with human astrovirus 1, we confirm initiation at the ORFX AUG. XP-knockout astroviruses are strongly attenuated and after passaging can partly restore viral titer via pseudo-reversions, thus demonstrating that XP plays an important role in virus growth. To further investigate XP, we developed an astrovirus replicon system. We demonstrate that XP has only minor effects on RNA replication and structural protein production. Instead, XP associates with the plasma membrane with an extracellular N-terminus topology and promotes efficient virus release. Using two different assays, we show that expression of human or related astrovirus XPs leads to cell permeabilization, suggesting a viroporin-like activity. The discovery of XP advances our knowledge of these important human viruses and opens a new direction of research into astrovirus replication and pathogenesis.",2019-06-06,"Lulla, V.; Firth, A. E.",,,,True
e4d752fd72eb7b1089e4b820598b1f69f50bc636,biorxiv,"Nowcasting by Bayesian Smoothing: A flexible, generalizable model for real-time epidemic tracking",doi.org/10.1101/663823,,,See https://www.biorxiv.org/about-biorxiv,"Delays in case reporting are common to disease surveillance systems, making it difficult to track diseases in real-time. \""Nowcast\"" approaches attempt to estimate the complete case counts for a given reporting date, using a time series of case reports that is known to be incomplete due to reporting delays. Modeling the reporting delay distribution is a common feature of nowcast approaches. However, many nowcast approaches ignore a crucial feature of infectious disease transmission--that future cases are intrinsically linked to past reported cases--and are optimized to a single application, which may limit generalizability. Here, we present a Bayesian approach, NobBS (Nowcasting by Bayesian Smoothing) capable of producing smooth and accurate nowcasts in multiple disease settings. We test NobBS on dengue in Puerto Rico and influenza-like illness (ILI) in the United States to examine performance and robustness across settings exhibiting a range of common reporting delay characteristics (from stable to time-varying), and compare this approach with a published nowcasting package. We show that introducing a temporal relationship between cases considerably improves performance when the reporting delay distribution is time-varying, and we identify trade-offs in the role of moving windows to accurately capture changes in the delay. We present software implementing this new approach (R package \""NobBS\"") for widespread application.\n\nSignificanceAchieving accurate, real-time estimates of disease activity is challenged by delays in case reporting. However, approaches that seek to estimate cases in spite of reporting delays often do not consider the temporal relationship between cases during an outbreak, nor do they identify characteristics of robust approaches that generalize to a wide range of surveillance contexts with very different reporting delays. Here, we present a smooth Bayesian nowcasting approach that produces accurate estimates that capture the time evolution of the epidemic curve and outperform a previous approach in the literature. We assess the performance for two diseases to identify important features of the reporting delay distribution that contribute to the models performance and robustness across surveillance settings.",2019-06-07,"McGough, S. F.; Johansson, M. A.; Lipsitch, M.; Menzies, N. A.",,,,True
fe09ebcf10de441c0ad0a90f0926ec0aed5a0577,biorxiv,A case for a reverse-frame coding sequence in a group of positive-sense RNA viruses,doi.org/10.1101/664342,,,See https://www.biorxiv.org/about-biorxiv,"Positive-sense single-stranded RNA viruses form the largest and most diverse group of eukaryote-infecting viruses. Their genomes comprise one or more segments of coding-sense RNA that function directly as messenger RNAs upon release into the cytoplasm of infected cells. Positive-sense RNA viruses are generally accepted to encode proteins solely on the positive strand. However, we previously identified a surprisingly long (~1000 codons) open reading frame (ORF) on the negative strand of some members of the family Narnaviridae which, together with RNA bacteriophages of the family Leviviridae, form a sister group to all other positive-sense RNA viruses. Here, we completed the genomes of three mosquito-associated narnaviruses, all of which have the long reverse-frame ORF. We systematically identified narnaviral sequences in public data sets from a wide range of sources, including arthropod, fungi and plant transcriptomic datasets. Long reverse-frame ORFs are widespread in one clade of narnaviruses, where they frequently occupy >95% of the genome. The reverse-frame ORFs correspond to a specific avoidance of CUA, UUA and UCA codons (i.e. stop codon reverse complements) in the forward-frame RNA-dependent RNA polymerase ORF. However, absence of these codons cannot be explained by other factors such as inability to decode these codons or GC3 bias. Together with other analyses, we provide the strongest evidence yet of coding capacity on the negative strand of a positive-sense RNA virus. As these ORFs comprise some of the longest known overlapping genes, their study may be of broad relevance to understanding overlapping gene evolution and de novo origin of genes.",2019-06-10,"Dinan, A. M.; Lukhovitskaya, N. I.; Olendraite, I.; Firth, A. E.",,,,True
31e67053158e68f513214a7a33046b5cc5f26249,biorxiv,"Decoupling the effects of nutrition, age and behavioral caste on honey bee physiology and immunity",doi.org/10.1101/667931,,,See https://www.biorxiv.org/about-biorxiv,"Nutritional stress, and especially a dearth of pollen, is considered an important factor associated with honey bee colony losses. We used pollen-restricted colonies as a model to study the nutritional stress conditions experienced in colonies within intensively cultivated agricultural areas. This model was complemented by the establishment of an experimental design, which allowed us to uncouple the effect of nutrition, behavior and age in colonies of similar size and demography. We used this system to determine the effect of pollen restriction on workers behavioral development. Then, we analyzed the effect of nutritional stress, behavior and age on the expression of key physiological genes involved in the regulation of division of labor. Finally, we analyzed the effects of these variables on the expression of immune genes and the titers of honey bee viruses. Our results show that pollen restriction led to an increased number of precocious foragers and this behavioral transition was associated with important changes in the expression of nutritionally regulated physiological genes, immunity and viral titers. Vitellogenin (vg) and major royal jelly protein 1 (mrjp1) were the most predictive markers of nutrition and behavior. The expression of immune genes was primarily affected by behavior, with higher levels in foragers. Deformed wing virus (DWV) titers were significantly affected by behavior and nutritional status, with higher titer in foragers and increased levels associated with pollen ingestion. Correlation analyses support the predominant effect of behavior on immunity and susceptibility to viral infection, revealing that both immune genes and DWV exhibited strong negative correlations with genes associated with nursing, but positive correlations with genes associated with foraging. Our results provide valuable insights into the physiological mechanisms by which nutritional stress induce precocious foraging and increased susceptibility to viral infections.",2019-06-11,"Corona, M.; Branchiccela, B.; Madella, S.; Chen, Y.; Evans, J. D.",,,,True
50688ca74af7fb4395c03e3cf7ec3bddc84e6165,biorxiv,In-vivo targeted tagging of RNA isolates cell specific transcriptional responses to environmental stimuli and identifies liver-to-adipose RNA transfer,doi.org/10.1101/670398,,,See https://www.biorxiv.org/about-biorxiv,"Bio-fluids contain various circulating cell-free RNA transcripts (ccfRNAs). The composition of these ccfRNAs varies between bio-fluids and constitute tantalizing biomarker candidates for several pathologies. ccfRNAs have also been demonstrated as mediators of cellular communication, yet little is known about their function in physiological and developmental settings and most works are limited to in-vitro studies. Here, we have developed iTAG-RNA, a novel method for the unbiased tagging of RNA transcripts in mice in-vivo. We used this method to isolate hepatocytes and kidney proximal epithelial cells-specific transcriptional response to a dietary challenge without interfering with the tissue architecture, and to identify multiple hepatocyte-secreted ccfRNAs in plasma. We also identified transfer of these hepatic derived ccfRNAs to adipose tissue, where they likely serve as a buffering mechanism to maintain cholesterol and lipid homeostasis. Our findings directly demonstrate in-vivo transfer of RNAs between tissues and highlight its implications for endocrine signaling and homeostasis.",2019-06-14,"Darr, J.; Lassi, M.; Tomar, A.; Gerlini, R.; Scheid, F.; Hrabe de Angelis, M.; Witting, M.; Teperino, R.",,,,True
1f783a5e029f80516169b19fe6e0dacc1e171f87,biorxiv,Metagenomic Nanopore sequencing of influenza virus direct from clinical respiratory samples,doi.org/10.1101/676155,,,See https://www.biorxiv.org/about-biorxiv,"Influenza is a major global public health threat as a result of its highly pathogenic variants, large zoonotic reservoir, and pandemic potential. Metagenomic viral sequencing offers the potential of a diagnostic test for influenza which also provides insights on transmission, evolution and drug resistance, and simultaneously detects other viruses. We therefore set out to apply Oxford Nanopore Technology to metagenomic sequencing of respiratory samples. We generated influenza reads down to a limit of detection of 102-103 genome copies/ml in pooled samples, observing a strong relationship between the viral titre and the proportion of influenza reads (p = 4.7x10-5). Applying our methods to clinical throat swabs, we generated influenza reads for 27/27 samples with high-to-mid viral titres (Cycle threshold (Ct) values <30) and 6/13 samples with low viral titres (Ct values 30-40). No false positive reads were generated from 10 influenza-negative samples. Thus Nanopore sequencing operated with 83% sensitivity (95% CI 67-93%) and 100% specificity (95% CI 69-100%) compared to the current diagnostic standard. Coverage of full length virus was dependent on sample composition, being negatively influenced by increased host and bacterial reads. However, at high influenza titres, we were able to reconstruct >99% complete sequence for all eight gene segments. We also detected Human Coronavirus and generated a near complete Human Metapneumovirus genome from clinical samples. While further optimisation is required to improve sensitivity, this approach shows promise for the Nanopore platform to be used in the diagnosis and genetic analysis of influenza and other respiratory viruses.",2019-06-19,"Lewandowski, K.; Xu, Y.; Pullan, S. T.; Foster, D.; Sanderson, N. D.; Vaughan, A.; Morgan, M.; Bright, N.; Kavanagh, J.; Vipond, R. T.; Carroll, M. W.; Marriott, A. C.; Gooch, K. E.; Andersson, M.; Jeffery, K.; Peto, T. E. A.; Crook, D. W.; Walker, A. S.; Matthews, P. C.",,,,True
8aa021696a6accab9053f1d779eef6710439bfa5,biorxiv,Quantifying transmission of emerging zoonoses: Using mathematical models to maximize the value of surveillance data,doi.org/10.1101/677021,,,See https://www.biorxiv.org/about-biorxiv,"Understanding and quantifying the transmission of zoonotic pathogens is essential for directing public health responses, especially for pathogens capable of transmission between humans. However, determining a pathogens transmission dynamics is complicated by challenges often encountered in zoonotic disease surveillance, including unobserved sources of transmission (both human and zoonotic), limited spatial information, and unknown scope of surveillance. In this work, we present a model-based inference method that addresses these challenges for subcritical zoonotic pathogens using a spatial model with two levels of mixing. After demonstrating the robustness of the method using simulation studies, we apply the new method to a dataset of human monkeypox cases detected during an active surveillance program from 1982-1986 in the Democratic Republic of the Congo (DRC). Our results provide estimates of the reproductive number and spillover rate of monkeypox during this surveillance period and suggest that most human-to-human transmission events occur over distances of 30km or less. Taking advantage of contact-tracing data available for a subset of monkeypox cases, we find that around 80% of contact-traced links could be correctly recovered from transmission trees inferred using only date and location. Our results highlight the importance of identifying the appropriate spatial scale of transmission, and show how even imperfect spatiotemporal data can be incorporated into models to obtain reliable estimates of human-to-human transmission patterns.\n\nAuthor SummarySurveillance datasets are often the only sources of information about the ecology and epidemiology of zoonotic infectious diseases. Methods that can extract as much information as possible from these datasets therefore provide a key advantage for informing our understanding of the disease dynamics and improving our ability to choose the optimal intervention strategy. We developed and tested a likelihood-based inference method based on a mechanistic model of the spillover and human-to-human transmission processes. We first used simulated datasets to explore which information about the disease dynamics of a subcritical zoonotic pathogen could be successfully extracted from a line-list surveillance dataset with non-localized spatial information and unknown geographic coverage. We then applied the method to a dataset of human monkeypox cases detected during an active surveillance program in the Democratic Republic of the Congo between 1982 and 1986 to obtain estimates of the reproductive number, spillover rate, and spatial dispersal of monkeypox in humans.",2019-06-19,"Ambrose, M.; Kucharski, A. J.; Formenty, P.; Muyembe-Tamfum, J.-J.; Rimoin, A. W.; Lloyd-Smith, J. O.",,,,True
fda16c1ee2fbae3368f64a138aa27d972a83e020,biorxiv,Alphavirus nsP3 ADP-ribosylhydrolase Activity Disrupts Stress Granule Formation,doi.org/10.1101/629881,,,See https://www.biorxiv.org/about-biorxiv,"Formation of stress granules (SGs), cytoplasmic condensates of stalled translation initiation complexes, is regulated by post-translational protein modification. Alphaviruses interfere with SG formation in response to inhibition of host protein synthesis through the activities of nonstructural protein 3 (nsP3). nsP3 has a conserved N-terminal macrodomain that binds and can remove ADP-ribose from ADP-ribosylated proteins and a C-terminal hypervariable domain that binds essential SG component G3BP1. We showed that the hydrolase activity of chikungunya virus nsP3 macrodomain removed ADP-ribosylation of G3BP1 and suppressed SG formation. ADP-ribosylhydrolase-deficient nsP3 mutants allowed stress-induced cytoplasmic condensation of translation initiation factors. nsP3 also disassembled SG-like aggregates enriched with translation initiation factors that are induced by the expression of FUS mutant R495X linked to amyotrophic lateral sclerosis. Therefore, our data indicate that regulation of ADP-ribosylation controls the localization of translation initiation factors during virus infection and other pathological conditions.",2019-06-20,"Jayabalan, A. K.; Griffin, D. E.; Leung, A. K. L.",,,,True
c8e940f25e802de4fb2abd917b76b8dffc5a23ae,biorxiv,Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to metabolic stress,doi.org/10.1101/675785,,,See https://www.biorxiv.org/about-biorxiv,"Fasting paradigms elicit a wide-range of health benefits including suppressing inflammation. Exploring the molecular mechanisms that prevent inflammation during caloric restriction may yield promising new therapeutic targets. During fasting, activation of the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARA) promotes the utilization of lipids as an energy source. Herein, we show that ligand activation of PPARA directly upregulates the long non-coding RNA gene Gm15441 through binding sites within its promoter. Gm15441 expression suppresses its antisense transcript, encoding thioredoxin interacting protein (TXNIP). This, in turn, decreases TXNIP-stimulated NLRP3 inflammasome activation, caspase-1 (CASP1) cleavage, and proinflammatory interleukin 1 beta (IL1B) maturation. Gm15441-null mice were developed and shown to be more susceptible to NLRP3 inflammasome activation and to exhibit elevated CASP1 and IL1B cleavage in response to metabolic and inflammatory stimuli. These findings provide evidence for a novel mechanism by which PPARA attenuates hepatic inflammasome activation in response to metabolic stress through lncRNA Gm15441 induction.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC=\""FIGDIR/small/675785v1_ufig1.gif\"" ALT=\""Figure 1\"">\nView larger version (23K):\norg.highwire.dtl.DTLVardef@1db1d5dorg.highwire.dtl.DTLVardef@64c8b2org.highwire.dtl.DTLVardef@b4402borg.highwire.dtl.DTLVardef@1e0fbba_HPS_FORMAT_FIGEXP  M_FIG Graphical abstract\n\nC_FIG",2019-06-20,"Brocker, C. N.; Kim, D.; Melia, T.; Karri, K.; Velenosi, T. J.; Takahashi, S.; Bonzo, J. A.; Waxman, D. J.; Gonzalez, F. J.",,,,True
b1a5096c2bfbb4ab9826c36e3961929a744134ca,biorxiv,Inferring generation-interval distributions from contact-tracing data,doi.org/10.1101/683326,,,See https://www.biorxiv.org/about-biorxiv,"Generation intervals, defined as the time between when an individual is infected and when that individual infects another person, link two key quantities that describe an epidemic: the reproductive number, [Formula], and the rate of exponential growth, r. Generation intervals are often measured through contact tracing by identifying who infected whom. We study how observed intervals differ from \""intrinsic\"" intervals that could be estimated by tracing individual-level infectiousness, and identify both spatial and temporal effects, including censoring (due to observation time), and the effects of susceptible depletion at various spatial scales. Early in an epidemic, we expect the variation in the observed generation intervals to be mainly driven by the censoring and the population structure near the source of disease spread; therefore, we predict that correcting observed intervals for the effect of temporal censoring but not for spatial effects will provide a spatially informed \""effective\"" generation-interval distribution, which will correctly link r and [Formula]. We develop and test statistical methods for temporal corrections of generation intervals, and confirm our prediction using individual-based simulations on an empirical network.",2019-07-03,"Park, S. W.; Champredon, D.; Dushoff, J.",,,,True
224a389bd5dbeab45b8a25965298016fbc44d669,biorxiv,Establishment of primary transgenic human airway epithelial cell cultures to study respiratory virus-host interactions,doi.org/10.1101/694380,,,See https://www.biorxiv.org/about-biorxiv,"Primary human airway epithelial cell (hAEC) cultures represent a universal platform to propagate respiratory viruses and characterize their host interactions in authentic target cells. To further elucidate specific interactions between human respiratory viruses and important host factors in airway epithelium, it is important to make hAEC cultures amenable to genetic modification. However, the short and finite lifespan of primary cells in cell culture creates a bottleneck for the genetic modification of these cultures. In the current study, we show that the incorporation of the Rho-associated protein kinase (ROCK) inhibitor (Y-27632) during cell propagation extends the life span of primary human cells in vitro and thereby facilitates the incorporation of lentivirus-based expression systems. Using fluorescent reporters for FACS-based sorting, we generated homogenously fluorescent hAEC cultures that differentiate normally after lentiviral transduction. As proof-of-principle, we demonstrate that host gene expression can be modulated post-differentiation via inducible short hairpin (sh)RNA-mediated knockdown. Importantly, functional characterization of these transgenic hAEC cultures with exogenous poly(I:C), as a proxy for virus infection, demonstrates that such modifications do not influence the host innate immune response. Moreover, the propagation kinetics of both human coronavirus 229E (HCoV-229E) and human respiratory syncytial virus (RSV) were not affected. Combined, these results validate our newly established protocol for the genetic modification of hAEC cultures thereby unlocking a unique potential for detailed molecular characterization of virus - host interactions in human respiratory epithelium.",2019-07-08,"Jonsdottir, H. R.; Marti, S.; Geerts, D.; Rodriguez, R.; Thiel, V.; Dijkman, R.",,,,True
5daceb492bad28a61fc43c4be83a164042d8c430,biorxiv,Recombinant rotaviruses rescued by reverse genetics reveal the role of NSP5 hyperphosphorylation in the assembly of viral factories,doi.org/10.1101/660217,,,See https://www.biorxiv.org/about-biorxiv,"Rotavirus (RV) replicates in round-shaped cytoplasmic viral factories although how they assemble remains unknown.\n\nDuring RV infection, NSP5 undergoes hyperphosphorylation, which is primed by the phosphorylation of a single serine residue. The role of this post-translational modification in the formation of viroplasms and its impact on the virus replication remains obscure. Here we investigated the role of NSP5 during RV infection by taking advantage of a modified fully tractable reverse genetics system. An NSP5 trans-complementing cell line was used to generate and characterise several recombinant rotaviruses (rRVs) with mutations in NSP5. We demonstrate that a rRV lacking NSP5, was completely unable to assemble viroplasms and to replicate, confirming its pivotal role in rotavirus replication.\n\nA number of mutants with impaired NSP5 phosphorylation were generated to further interrogate the function of this post-translational modification in the assembly of replication-competent viroplasms. We showed that the rRV mutant strains exhibit impaired viral replication and the ability to assemble round-shaped viroplasms in MA104 cells. Furthermore, we have investigated the mechanism of NSP5 hyper-phosphorylation during RV infection using NSP5 phosphorylation-negative rRV strains, as well as MA104-derived stable transfectant cell lines expressing either wt NSP5 or selected NSP5 deletion mutants. Our results indicate that NSP5 hyper-phosphorylation is a crucial step for the assembly of round-shaped viroplasms, highlighting the key role of the C-terminal tail of NSP5 in the formation of replication-competent viral factories. Such a complex NSP5 phosphorylation cascade may serve as a paradigm for the assembly of functional viral factories in other RNA viruses.\n\nIMPORTANCERotavirus (RV) double-stranded RNA genome is replicated and packaged into virus progeny in cytoplasmic structures termed viroplasms. The non-structural protein NSP5, which undergoes a complex hyperphosphorylation process during RV infection, is required for the formation of these virus-induced organelles. However, its roles in viroplasm formation and RV replication have never been directly assessed due to the lack of a fully tractable reverse genetics (RG) system for rotaviruses. Here we show a novel application of a recently developed RG system by establishing a stable trans-complementing NSP5-producing cell line required to rescue rotaviruses with mutations in NSP5. This approach allowed us to provide the first direct evidence of the pivotal role of this protein during RV replication. Furthermore, using recombinant RV mutants we shed light on the molecular mechanism of NSP5 hyperphosphorylation during infection and its involvement in the assembly and maturation of replication-competent viroplasms.",2019-07-08,"Papa, G.; Venditti, L.; Arnoldi, F.; Schraner, E. M.; Potgieter, C.; Borodavka, A.; Eichwald, C.; Burrone, O. R.",,,,True
30814fcc87b8f3e5d4f7431d75b9505b049021e0,biorxiv,Zika virus infection in Collaborative Cross mice,doi.org/10.1101/695510,,,See https://www.biorxiv.org/about-biorxiv,"The 2015-2016 emergence of Zika virus (ZIKV) in the Americas, and recognition that ZIKV infection during pregnancy can result in birth defects, revealed a need for small animal models to study ZIKV pathogenic mechanisms and evaluate candidate vaccines and antivirals. Mice would be an attractive system for such studies, but ZIKV replicates poorly in laboratory mice because it fails to antagonize murine STAT2 and STING. To address this, most ZIKV pathogenesis studies have used mice with impaired interferon signaling (e.g. Ifnar1-/- or treatment with IFNAR1-blocking antibodies). However, using mice with severe defects in innate antiviral signaling confounds studies of viral pathogenic mechanisms. Collaborative Cross (CC) mice have proven to be a valuable system for developing new mouse pathogenesis models for viral infections that are not well modeled in conventional laboratory mouse lines. To test whether CC mice could provide an immune-competent model for ZIKV pathogenesis, we infected CC lines with ZIKV and assessed weight loss, viremia, and production of neutralizing antibodies. We tested 21 CC lines (CC001, CC002, CC003, CC004, CC005, CC006, CC011, CC012, CC013, CC019, CC024, CC028, CC040, CC041, CC042, CC046, CC051, CC059, CC061, CC068, and CC072, 13 of which have non-functional alleles of the flavivirus restriction factor Oas1b) and 3 ZIKV strains (MR766, H/PF/2013, and a mouse-adapted variant of Dakar 41525). ZIKV infection did not induce weight loss compared to mock-infected controls and accordingly only low levels of viral RNA were detected in serum. Only a subset of mice developed neutralizing antibodies to ZIKV, likely due to overall low levels of infection and viremia. Our results are consistent with other studies demonstrating poor ZIKV infection in interferon-intact mice and suggest that the tested CC lines do not include polymorphic host genes that greatly increase susceptibility to ZIKV infection.",2019-07-08,"Mattocks, M. D.; Plante, K. S.; Fritch, E. J.; Baric, R. S.; Ferris, M. T.; Heise, M. T.; Lazear, H. M.",,,,True
685cdc49b5db13ec22f0eda615b026bf59cd23f4,biorxiv,Viral long-term evolutionary strategies favor stability over proliferation,doi.org/10.1101/539239,,,See https://www.biorxiv.org/about-biorxiv,"Viruses are known to have some of the highest and most diverse mutation rates found in any biological replicator, topped by single-stranded (ss) RNA viruses, while double-stranded (ds) DNA viruses have rates approaching those of bacteria. As mutation rates are tightly and negatively correlated with genome size, selection is a clear driver of viral evolution. However, the role of intragenomic interactions as drivers of viral evolution is less well documented. To understand how these two processes affect viral evolution, we systematically surveyed ssRNA, ssDNA, dsRNA, and dsDNA viruses, to find which virus type and which functions show evidence for episodic diversifying selection and correlated evolution. We show that while evidence for selection is mostly found in single stranded viruses, and correlated evolution is more prevalent in DNA viruses, the genes that are affected by both processes are involved in key aspects of their life cycle, favoring viral stability over proliferation. We further show that both evolutionary processes are intimately linked at the amino acid level, which suggests that selection alone does not explain the whole evolutionary --and epidemiological-- potential of viruses.",2019-07-12,"Aris-Brosou, S.; Parent, L.; Ibeh, N.",,,,True
d14f165645f21a60d224c6286c5e51799797eceb,biorxiv,Collaborative Cross Mouse Populations as a Resource for the Study of Epilepsy,doi.org/10.1101/690917,,,See https://www.biorxiv.org/about-biorxiv,"Epilepsy is a neurological disorder with complex etiologies and genetic architecture. Animal models have a critical role in understanding the pathophysiology of epilepsy. Here we studied epilepsy utilizing a genetic reference population of Collaborative Cross (CC) mice with publicly available whole genome sequences. We measured multiple epilepsy traits in 35 CC strains, and we identified novel animal models that exhibit extreme outcomes in seizure susceptibility, seizure propagation, epileptogenesis, and sudden unexpected death in epilepsy. We performed QTL mapping in an F2 population and identified seven novel and one previously identified loci associated with seizure sensitivity. We combined whole genome sequence and hippocampal gene expression to pinpoint biologically plausible candidate genes and candidate variants associated with seizure sensitivity. These resources provide a powerful toolbox for studying complex features of seizures and for identifying genes associated with particular seizure outcomes, and hence will facilitate the development of new therapeutic targets for epilepsy.",2019-07-15,"Gu, B.; Shorter, J. R.; Williams, L. H.; Bell, T. A.; Hock, P.; Dalton, K. A.; PAN, Y.; Miller, D. R.; Shaw, G. D.; Cooley, B. C.; Philpot, B. D.; Pardo Manuel de Villena, F.",,,,True
4c35605124dd8011395240fac71e80b52ddbbe7e,biorxiv,A binning tool to reconstruct viral haplotypes from assembled contigs,doi.org/10.1101/704288,,,See https://www.biorxiv.org/about-biorxiv,"MotivationInfections by RNA viruses such as Influenza, HIV still pose a serious threat to human health despite extensive research on viral diseases. One challenge for producing effective prevention and treatment strategies is high intra-species genetic diversity. As different strains may have different biological properties, characterizing the genetic diversity is thus important to vaccine and drug design. Next-generation sequencing technology enables comprehensive characterization of both known and novel strains and has been widely adopted for sequencing viral populations. However, genome-scale reconstruction of haplotypes is still a challenging problem. In particular, haplotype assembly programs often produce contigs rather than full genomes. As a mutation in one gene can mask the phenotypic effects of a mutation at another locus, clustering these contigs into genome-scale haplotypes is still needed.\n\nResultsWe developed a contig binning tool, VirBin, which clusters contigs into different groups so that each group represents a haplotype. Commonly used features based on sequence composition and contig coverage cannot effectively distinguish viral haplotypes because of their high sequence similarity and heterogeneous sequencing coverage for RNA viruses. VirBin applied prototype-based clustering to cluster regions that are more likely to contain mutations specific to a haplotype. The tool was tested on multiple simulated sequencing data with different haplotype abundance distributions and contig sizes, and also on mock quasispecies sequencing data. The benchmark results with other contig binning tools demonstrated the superior sensitivity and precision of VirBin in contig binning for viral haplotype reconstruction.\n\nAvailabilityhttps://github.com/chjiao/VirBin\n\nContactyannisun@cityu.edu.hk",2019-07-16,"Chen, J.; Shang, J.; Wang, J.; Sun, Y.",,,,True
402041df2d9812dbcdae08153d0350eee170eea9,biorxiv,Chemogenetic evidence that rapid neuronal de novo protein synthesis is required for consolidation of long-term memory,doi.org/10.1101/704965,,,See https://www.biorxiv.org/about-biorxiv,"Translational control of memory processes is a tightly regulated process where the coordinated interaction and modulation of translation factors provides a permissive environment for protein synthesis during memory formation. Existing methods used to block translation lack the spatiotemporal precision to investigate cell-specific contributions to consolidation of long-term memories. Here, we have developed a novel chemogenetic mouse resource for cell type-specific and drug-inducible protein synthesis inhibition (ciPSI) that utilizes an engineered version of the catalytic kinase domain of dsRNA-activated protein (PKR). ciPSI allows rapid and reversible phosphorylation of eIF2 causing a block on general translation by 50% in vivo. Using this resource, we discovered that temporally structured pan-neuronal protein synthesis is required for consolidation of long-term auditory threat memory. Targeted protein synthesis inhibition in CamK2 expressing glutamatergic neurons in lateral amygdala (LA) impaired long-term memory, which was recovered with artificial chemogenetic reactivation at the cost of stimulus generalization. Conversely, genetically reducing phosphorylation of eIF2 in CamK2 positive neurons in LA enhanced memory strength, but was accompanied with reduced memory fidelity and behavior inflexibility. Our findings provide evidence for a finely tuned translation program during consolidation of long-term threat memories.",2019-07-17,"Shrestha, P.; Ayata, P.; Herrero Vidal, P. M.; Longo, F.; Gastone, A.; LeDoux, J.; Heintz, N.; Klann, E.",,,,True
2e5d79e1e6ebeed6cffdad2b474ca7675da969e7,biorxiv,"Quantifying the roles of vomiting, diarrhea, and residents vs. staff in norovirus transmission in U.S. nursing home outbreaks",doi.org/10.1101/707356,,,See https://www.biorxiv.org/about-biorxiv,"The role of individual case characteristics, such as symptoms or demographics, in norovirus transmissibility is poorly understood. Six nursing home norovirus outbreaks occurring in South Carolina, U.S. from 2014 to 2016 were examined. We aimed to quantify the contribution of symptoms and other case characteristics in norovirus transmission using the reproduction number (REi) as an estimate of individual case infectivity and to examine how transmission changes over the course of an outbreak. Individual estimates of REi were calculated using a maximum likelihood procedure to infer the average number of secondary cases generated by each case. The associations between case characteristics and REi were estimated using a multivariate mixed linear model. Outbreaks began with one to three index case(s) with large estimated REis (range: 1.48 to 8.70) relative to subsequent cases. Of the 209 cases, 155 (75%) vomited, 164 (79%) had diarrhea, and 158 (76%) were nursing home residents (vs. staff). Cases who vomited infected 2.74 (95% CI: 1.90, 3.94) more individuals than non-vomiters, cases with diarrhea infected 1.62 (95% CI: 1.09, 2.41) more individuals than cases without diarrhea, and resident-cases infected 1.69 (95% CI: 1.18, 2.42) more individuals than staff-cases. Index cases tended to be residents (vs. staff) who vomited and infected considerably more secondary cases compared to non-index cases. Results suggest that individuals, particularly residents, who vomit are more infectious and tend to drive norovirus transmission in U.S. nursing home norovirus outbreaks. While diarrhea also plays a role in norovirus transmission, it is to a lesser degree than vomiting in these settings. Results lend support for prevention and control measures that focus on cases who vomit, particularly if those cases are residents.\n\nAuthor summaryThe majority of all norovirus outbreaks reported to the CDC occur in long-term care facilities (LTCFs), including nursing homes, where older residents are at risk for more severe or prolonged infection. Because there is currently no publicly available norovirus vaccine, sound control measures are key to controlling norovirus outbreaks, but there is little evidence that standard control measures are effective in reducing the size and/or duration of LTCF norovirus outbreaks. Hence, studies leading to a better understanding of disease spread and prevention of additional cases, and thus more effective control measures, are needed. To this end, we aimed to quantify factors associated with norovirus transmission and to examine how transmission changes over the course of an outbreak. We show that vomiting and, to a lesser extent, diarrhea are critical in initiating and sustaining norovirus transmission in U.S. nursing home norovirus outbreaks. We also show that nursing home residents, rather than staff, are the primary drivers of transmission. Results suggest that control measures focusing on cases who vomit, particularly if those cases are residents, would be most effective at curtailing norovirus transmission in these settings.",2019-07-18,"Adams, C.; Young, D.; Gastanaduy, P. A.; Paul, P.; Marsh, Z.; Hall, A. J.; Lopman, B. A.",,,,True
9c32d461dc9d4737756a990cf13bae1a03e078a9,biorxiv,MUC5AC drives COPD exacerbation severity through amplification of virus-induced airway inflammation,doi.org/10.1101/706804,,,See https://www.biorxiv.org/about-biorxiv,"The respiratory tract surface is protected from inhaled pathogens by a secreted layer of mucus that is rich in mucin glycoproteins. Disrupted mucus production is a cardinal feature of chronic respiratory diseases but how this alteration affect interactions between mucins and pathogens is complex and poorly understood. Here, we identify a central and unexpected role for the major airway mucin MUC5AC in pathogenesis of virus-induced exacerbations of chronic obstructive pulmonary disease (COPD). Virus induction of MUC5AC is augmented in COPD compared to healthy subjects, is enhanced in frequent exacerbators and correlates with inflammation, symptom severity and secondary bacterial infection during exacerbation. MUC5AC is functionally related to inflammation as MUC5AC-deficient (Muc5ac-/-) mice had attenuated rhinovirus-induced airway inflammation whilst exogenous MUC5AC glycoprotein administration augmented virus-induced inflammatory responses and bacterial load. Mechanistically, MUC5AC-augmentation of rhinovirus-induced inflammation occurred through release of extracellular adenosine triphosphate (ATP). Therapeutic suppression of virus-induced MUC5AC release using an epidermal growth factor receptor (EGFR) inhibitor ameliorated exaggerated pro-inflammatory responses in a mouse COPD exacerbation model. Collectively, these studies demonstrate previously unrecognised pro-inflammatory effects of MUC5AC during infection and thus highlight a key unforeseen role in driving COPD exacerbation severity.",2019-07-22,"Singanayagam, A.; Footitt, J.; Kasdorf, B. T.; Marczynski, M.; Cross, M. T.; Finney, L. J.; Trujillo Torralbo, M.-B.; Calderazzo, M.; Zhu, J.; Aniscenko, J.; Clarke, T. B.; Molyneaux, P. L.; Bartlett, N. W.; Moffatt, M. F.; Cookson, W. O.; Wedzicha, J.; Evans, C. M.; Lieleg, O.; Mallia, P.; Johnston, S. L.",,,,True
bfb0852ef4dd124ba671303aee7a71a08c7c21a7,biorxiv,An automated data processing and analysis pipeline for transmembrane proteins in detergent solutions,doi.org/10.1101/714303,,,See https://www.biorxiv.org/about-biorxiv,"The application of small angle X-ray scattering (SAXS) to the structural characterization of transmembrane proteins (MPs) in detergent solutions has become a routine procedure at the most synchrotron BioSAXS beamlines around the world. SAXS provides overall parameters and low resolution shapes of solubilized MPs, but is also meaningfully employed in hybrid modeling procedures that combine scattering data with information provided by high-resolution techniques (eg. macromolecular crystallography, nuclear magnetic resonance and cryo-electron microscopy). Structural modeling of MPs from SAXS data is non-trivial, and the necessary computational procedures require further formalization and facilitation. We propose an automated pipeline integrated with the laboratory-information management system ISPyB, aimed at preliminary SAXS analysis and the first-step reconstruction of MPs in detergent solutions, in order to streamline high-throughput studies, especially at synchrotron beamlines. The pipeline queries an ISPyB database for available a priori information via dedicated services, estimates model-free SAXS parameters and generates preliminary models utilizing either ab initio, high-resolution-based, or mixed/hybrid methods. The results of the automated analysis can be inspected online using the standard ISPyB interface and the estimated modeling parameters may be utilized for further in-depth modeling beyond the pipeline. Examples of the pipeline results for the modelling of the tetrameric alpha-helical membrane channel Aquaporin0 and mechanosensitive channel T2, solubilized by n-Dodecyl {beta}-D-maltoside are presented. We demonstrate how the increasing amount a priori information improves the model resolution and enables deeper insights into the molecular structure of protein-detergent complexes.\n\nSTATEMENT OF SIGNIFICANCESmall angle X-ray scattering (SAXS) using synchrotron radiation is a powerful technique for the structural characterization of transmembrane proteins (MPs) in detergent solutions Overall structural characterization and modeling of MPs from SAXS data is non-trivial, and the necessary computational procedures require further formalization and facilitation. We propose an automated pipeline integrated with the laboratory-information management system ISPyB, aimed at preliminary SAXS analysis and modelling of MPs in detergent solutions, in order to streamline high-throughput studies, especially at synchrotron beamlines.",2019-07-24,"Molodenskiy, D. S.; Mertens, H.; Svergun, D. I.",,,,True
f3c2b82a21fafc27e5da11b73ef722db96ddb19b,biorxiv,The porcine deltacoronavirus replication organelle comprises double membrane vesicles and zippered endoplasmic reticulum with double membrane spherules,doi.org/10.1101/719443,,,See https://www.biorxiv.org/about-biorxiv,"Porcine deltacoronavirus (PDCoV) was first identified in Hong Kong in 2012 from samples taken from pigs in 2009. PDCoV was subsequently identified in the USA in 2014 in pigs with a history of severe diarrhea and the virus has now been detected in pigs in several countries around the world. Following the development of tissue culture adapted strains of PDCoV, it is now possible to begin to address questions regarding virus-host cell interactions for this genera of coronavirus. Here we present a detailed study of PDCoV induced replication organelles. All positive strand RNA viruses induce the rearrangement of cellular membranes during virus replication to support viral RNA synthesis, forming the replication organelle. Replication organelles for the Alpha-, Beta- and Gammacoronavirus genera have been characterized. However the structures induced by deltacoronaviruses, in particular the presence of convoluted membranes or double membrane spherules, are unknown. Initially, the dynamics of PDCoV strain OH-FD22 replication were assessed with the onset of viral RNA synthesis, protein synthesis and progeny particle release determined. Subsequently, virus induced membrane rearrangements were identified in infected cells by electron microscopy. As has been observed for all other coronaviruses studied to date, PDCoV replication was found to induce the formation of double membrane vesicles. Significantly however, PDCoV replication was also found to induce the formation of regions of zippered endoplasmic reticulum and small associated tethered vesicles, double membrane spherules. These structures strongly resemble the replication organelle induced by avian Gammacoronavirus infectious bronchitis virus.",2019-07-31,"Doyle, N.; Hawes, P. C.; Simpson, J.; Adams, L. H.; Maier, H.",,,,False
9fb5ca87ca47d35d87161158ae37fc0ca642c51e,biorxiv,A Mac2-positive progenitor-like microglial population survives independent of CSF1R signaling in adult mouse brain,doi.org/10.1101/722090,,,See https://www.biorxiv.org/about-biorxiv,"Microglia are the resident myeloid cells in the central nervous system (CNS). The majority of microglial population relies on Csf1r signaling for survival and maintenance. However, a small subset of microglia in the murine brain can survive without Csf1r signaling, and reestablishes homeostasis after Csf1r signaling returns. Using single-cell RNA-seq, we characterized the heterogeneous microglial populations under Csf1r inhibition, including microglia lacking homeostatic markers and populations with elevated markers of monocytes, granulocytes and dendritic cells. Importantly, Mac2 is distinctively expressed in a subset of Csf1r-independent microglia cells, which were highly proliferative and shared striking similarities with those of microglial progenitors in yolk sac and early embryos. Lineage-tracing revealed that the Mac2+ population is of microglial origin and does not come from periphery monocytes. In non-treated mouse brains, Mac2+ microglia exhibited progenitor transcriptomic signature indistinguishable from those survived csf1r inhibition, supporting Mac2+ progenitor-like cells are present among homeostatic microglia.",2019-08-01,"Zhan, L.; Sohn, P. D.; Zhou, Y.; Li, Y.; Gan, L.",,,,True
92860a0f4425d12aafb8e096d8e65d38eb67dff5,biorxiv,Mutation of Ebola virus VP35 Ser129 uncouples interferon antagonist and replication functions,doi.org/10.1101/726935,,,See https://www.biorxiv.org/about-biorxiv,"Ebolaviruses are non-segmented, negative-sense RNA viruses (NNSVs) within the order Mononegavirales that possess the multifunctional virion protein 35 (VP35), a major determinant of virulence and pathogenesis that is indispensable for viral replication and host innate immune evasion. VP35 is functionally equivalent to the phosphoprotein (P) of other mononegaviruses such as rhabdoviruses and paramyxoviruses. Phosphorylation of the P protein is universally regarded as functionally important however, a regulatory role(s) of phosphorylation on VP35 function remains unexplored. Here, we identified a highly conserved Ser129 residue near the homo-oligomerization coiled coil motif, which is essential for VP35 functions. Affinity-purification MS followed by post-translational modification (PTM) analysis predicted phosphorylation of Ser129. Co-immunoprecipitation, cross-linking, and biochemical characterization studies revealed a moderately decreased capacity of VP35-S129A to oligomerize. Functional analysis showed that Ser-to-Ala substitution of Ebola virus (EBOV) VP35 did not affect IFN inhibitory activity but nearly abolished EBOV minigenome activity. Further coimmunoprecipitation studies demonstrated a lost interaction between VP35-S129A and the amino terminus of the viral polymerase but not between viral nucleoprotein (NP) or VP35-WT. Taken together, our findings provide evidence that phosphorylation modulates VP35 function, supporting VP35 as a NNSV P protein and providing a potentially valuable therapeutic target.\n\nImportanceEbola virus (EBOV) can cause severe disease in humans. The 2013-2016 West African epidemic and the two recent outbreaks in the Democratic Republic of the Congo underscore the urgent need for effective countermeasures, which remain lacking. A better understanding of EBOV biology and the modulation of multifunctional viral proteins is desperately needed to develop improved therapeutics. We provide evidence here that function of virion protein 35 (VP35) is modulated by phosphorylation of Ser129, a conserved residue among other ebolavirus species. These findings shed light on EBOV biology and present a potential target for broad acting anti-ebolavirus therapeutics.",2019-08-07,"Morwitzer, M. J.; Corona, A.; Zinzula, L.; Fanunza, E.; Nigri, C.; Distinto, S.; Vornholt, C.; Kumar, V.; Tramontano, E.; Reid, S. P.",,,,True
f0cd43222c9a51d619357babc4d0ac984e8e45a0,biorxiv,Alpha herpesvirus egress and spread from neurons uses constitutive secretory mechanisms independent of neuronal firing activity,doi.org/10.1101/729830,,,See https://www.biorxiv.org/about-biorxiv,"Alpha herpesviruses naturally infect the peripheral nervous system, and can spread to the central nervous system causing severe deadly or debilitating disease. Because alpha herpesviruses spread along synaptic circuits, and infected neurons exhibit altered electrophysiology and increased spontaneous firing, we hypothesized that alpha herpesviruses use activity-dependent synaptic vesicle-like regulated secretory mechanisms for egress and spread from neurons. To address this hypothesis, we used a compartmentalized primary neuron culture system to measure egress and spread of pseudorabies virus (PRV), pharmacological and optogenetics approaches to modulate neuronal firing activity, and a live-cell fluorescence microscopy assay to directly visualize the exocytosis of individual virus particles from infected neurons. Using tetrodotoxin to silence neuronal activity, we observed no inhibition of virus spread, and using potassium chloride or optogenetics to elevate neuronal activity, we also show no increase in virus spread. Using a live-cell fluorescence microscopy method to directly measure virus egress from infected neurons, we observed no association between virus particle exocytosis and intracellular Ca2+ signaling. Finally, we observed virus particle exocytosis occurs in association with constitutive secretory Rab GTPases, Rab6a and Rab8a, not Rab proteins that are associated with the Ca2+-regulated secretory pathway in neurons, Rab3a and Rab11a. Therefore, we conclude that alpha herpesvirus egress and spread is independent of neuronal activity and Ca2+ signaling because virus particle exocytosis uses constitutive secretory mechanisms in neurons.\n\nAuthor SummaryAlpha herpesviruses, including important human pathogens Herpes Simplex Virus 1 and 2, and Varicella-Zoster Virus, are among the very few viruses that naturally infect the nervous system. These viruses cause recurrent herpetic and zosteriform lesions, peripheral neuropathies, and deadly or debilitating central nervous system diseases. Many of the molecular and cellular mechanisms of viral egress and spread remain unknown, particularly in the context of specialized neuronal cell biology. Our results indicate that elevated firing activity of infected neurons is not functionally or mechanistically linked to virus egress and spread; therefore, therapies targeting peripheral neuropathic symptoms, elevated neuronal activity, and synaptic vesicle secretory mechanisms are unlikely to affect virus spread in the nervous system.",2019-08-08,"Ambrosini, A. E.; Deshmukh, N.; Berry, M. J.; Enquist, L. W.; Hogue, I. B.",,,,True
2dc6766fe253b1b832d8a3074404fb5daae4762f,biorxiv,Transferrin binding protein B and Transferrin binding protein A2 expand the transferrin recognition range of Histophilus somni,doi.org/10.1101/730739,,,See https://www.biorxiv.org/about-biorxiv,"The bacterial bipartite transferrin receptor is an iron acquisition system that is required for survival by several key human and animal pathogens. It consists of the TonB-dependent transporter Transferrin binding protein A (TbpA) and the surface lipoprotein Transferrin binding protein B (TbpB). Curiously, the Tbps are only found in host specific pathogens, and are themselves host specific, meaning that they will bind to the transferrin of their host species, but not to those of other animal species. While this phenomenon has long been established, neither the steps in the evolutionary process that led to this exquisite adaptation for the host, nor the steps that could alter it, are known. We sought to gain insight into these processes by studying Tbp specificity in Histophilus somni, a major pathogen of cattle. A past study showed that whole cells of H. somni specifically bind bovine transferrin, but not transferrin from sheep and goats, two bovids whose transferrins share 93% amino acid sequence identity with bovine transferrin. To our surprise, we found that H. somni can use sheep and goat transferrins as iron sources for growth, and that HsTbpB, but not HsTbpA, has detectable affinity for sheep and goat transferrins. Furthermore, a third transferrin binding protein, HsTbpA2, also showed affinity for sheep and goat transferrins. Our results show that H. somni TbpB and TbpA2 act to broaden the host transferrin recognition range of H. somni.\n\nImportanceHost restricted pathogens infect a single host species or a narrow range of host species. Histophilus somni, a pathogen that incurs severe economic losses for the cattle industry, infects cattle, sheep, and goats, but not other mammals. The transferrin binding proteins, TbpA and TbpB, are thought to be a key iron acquisition system in H. somni, however, surprisingly, they were also shown to be cattle transferrin-specific. In our study we find that H. somni TbpB, and another little-studied Tbp, TbpA2, bind sheep and goat transferrins as well as bovine transferrin. Our results suggest that TbpA2 may have allowed for host range expansion, and provide a mechanism for how host specificity in Tbp containing pathogens can be altered.",2019-08-09,"Pogoutse, A. K.; Moraes, T.",,,,True
7d91bba210d98289dac830135c56c13e206837ec,biorxiv,The role of post-Golgi transport pathways and sorting motifs in the plasmodesmal targeting of the movement protein (MP) of Ourmia melon virus (OuMV),doi.org/10.1101/724716,,,See https://www.biorxiv.org/about-biorxiv,"Plants have a highly sophisticated endomembrane system that is targeted by plant viruses for cell-to-cell movement. The movement protein (MP) of Ourmia melon virus (OuMV) is targeted to plasmodesmata (PD) and forms tubules to facilitate cell-to-cell movement. Despite a number of functionally important regions for correct subcellular localization of OuMV MP has been identified, little is known about the pathways OuMV MP hijacks to reach PD. Here, we demonstrate that OuMV MP localizes to the trans-Golgi network (TGN), but not to the multivesicular body/prevacuolar compartment or Golgi, and carries two putative sorting motifs, a tyrosine (Y) and a dileucine (LL) motif, near its N-terminus. Introducing glycine substitutions in these motifs results in loss of OuMV infectivity in Nicotiana benthamiana and Arabidopsis (Arabidopsis thaliana). Live cell imaging of GFP-labeled sorting motif mutants shows that Y motif mutants fail to localize to the TGN, plasma membrane, and PD. Mutations in the LL motif do not impair plasma membrane targeting of MP, but affect its ability to associate with callose deposits at PD. Taken together, these data suggest that both Y and LL motifs are indispensable for targeting of OuMV MP to PD and for efficient systemic infection, but show differences in functionality. This study provides new insights into the role of sorting motifs in intracellular targeting of MPs and vesicle trafficking pathways that plant viruses hijack for cell-to-cell movement.",2019-08-11,"Ozber, N.; Margaria, P.; Anderson, C. T.; Turina, M.; Rosa, C.",,,,True
681c5099b2afb08fe5cb2f58d92e9c6e4873bec2,biorxiv,Geometric coupling of helicoidal ramps and curvature-inducing proteins in organelle membranes,doi.org/10.1101/635466,,,See https://www.biorxiv.org/about-biorxiv,"Cellular membranes display an incredibly diverse range of shapes, both in the plasma membrane and at membrane bound organelles. These morphologies are intricately related to cellular functions, enabling and regulating fundamental membrane processes. However, the biophysical mechanisms at the origin of these complex geometries are not fully understood from the standpoint of membrane-protein coupling. In this work, we focused on a minimal model of helicoidal ramps representative of specialized endoplasmic reticulum compartments. Given a helicoidal membrane geometry, we asked what is the distribution of spontaneous curvature required to maintain this shape at mechanical equilibrium? Based on the Helfrich energy of elastic membranes with spontaneous curvature, we derived the shape equation for minimal surfaces, and applied it to helicoids. We showed the existence of switches in the sign of the spontaneous curvature associated with geometric variations of the membrane structures. Furthermore, for a prescribed gradient of spontaneous curvature along the exterior boundaries, we identified configurations of the helicoidal ramps that are confined between two infinitely large energy barriers. Overall our results suggest possible mechanisms for geometric control of helicoidal ramps in membrane organelles based on curvature-inducing proteins.",2019-08-12,"Chabanon, M.; Rangamani, P.",,,,True
36e602b7081e7bb8a1cfeaa2fb92b0c43abd4fef,biorxiv,Direct RNA nanopore sequencing of full-length coronavirus genomes provides novel insights into structural variants and enables modification analysis,doi.org/10.1101/483693,,,See https://www.biorxiv.org/about-biorxiv,"Sequence analyses of RNA virus genomes remain challenging due to the exceptional genetic plasticity of these viruses. Because of high mutation and recombination rates, genome replication by viral RNA-dependent RNA polymerases leads to populations of closely related viruses, so-called  quasispecies. Standard (short-read) sequencing technologies are ill-suited to reconstruct large numbers of full-length haplotypes of (i) RNA virus genomes and (ii) subgenome-length (sg) RNAs comprised of noncontiguous genome regions. Here, we used a full-length, direct RNA sequencing (DRS) approach based on nanopores to characterize viral RNAs produced in cells infected with a human coronavirus.\n\nUsing DRS, we were able to map the longest ([~]26 kb) contiguous read to the viral reference genome. By combining Illumina and nanopore sequencing, we reconstructed a highly accurate consensus sequence of the human coronavirus (HCoV) 229E genome (27.3 kb). Furthermore, using long reads that did not require an assembly step, we were able to identify, in infected cells, diverse and novel HCoV-229E sg RNAs that remain to be characterized. Also, the DRS approach, which circumvents reverse transcription and amplification of RNA, allowed us to detect methylation sites in viral RNAs. Our work paves the way for haplotype-based analyses of viral quasispecies by demonstrating the feasibility of intra-sample haplotype separation.\n\nEven though several technical challenges remain to be addressed to exploit the potential of the nanopore technology fully, our work illustrates that direct RNA sequencing may significantly advance genomic studies of complex virus populations, including predictions on long-range interactions in individual full-length viral RNA haplotypes.",2019-08-14,"Viehweger, A.; Krautwurst, S.; Lamkiewicz, K.; Madhugiri, R.; Ziebuhr, J.; Hölzer, M.; Marz, M.",,,,True
22a4d26bde67d878869443ea26140f3d8239bed0,biorxiv,Dissecting genetic and sex-specific host heterogeneity in pathogen transmission potential,doi.org/10.1101/733915,,,See https://www.biorxiv.org/about-biorxiv,"Heterogeneity in disease transmission is widespread and, when not accounted for, can produce unpredictable outbreaks of infectious disease. Despite this, precisely how different sources of variation in host traits drive heterogeneity in disease transmission is poorly understood. Here we dissected the sources of variation in pathogen transmission using Drosophila melanogaster and Drosophila C Virus as a host-pathogen model system. We found that infected lifespan, viral growth, virus shedding, and viral load at death were all significantly influenced by fly genetic background, sex and female mating status. To understand how variation in each of these traits may generate heterogeneity in disease transmission, we estimated individual transmission potential by integrating data on virus shedding and lifespan alongside previously collected data on social aggregation. We found that [~]15% of between-individual heterogeneity in disease transmission was explained by a significant interaction between genetic and sex-specific variation. We also characterised the amount of variation in viral load, virus shedding, and lifespan following infection that could be explained by genetic background and sex. Amongst the determinants of individual variation in disease transmission these sources of host variation play roles of varying importance, with genetic background generally playing the largest role. Our results highlight the importance of characterising sources of variation in multiple host traits when studying disease transmission at the individual-level.",2019-08-14,"Siva-Jothy, J. A.; Vale, P. F.",,,,True
311a15d92b87b2bc41f00afed881b95e93c22fcc,biorxiv,Comparative analysis reveals adaptive evolution of bat IFITMs and a novel antiviral determinant,doi.org/10.1101/737841,,,See https://www.biorxiv.org/about-biorxiv,"Host interferon-induced transmembrane proteins (IFITMs) are broad-spectrum antiviral restriction factors. Of these, IFITM3 potently inhibits viruses that enter cells through acidic endosomes, many of which are zoonotic and emerging viruses with bats (order Chiroptera) as natural hosts. We previously demonstrated that microbat IFITM3 is antiviral. Here we show that bat IFITMs are characterized by strong adaptive evolution and identify a highly variable and functionally important site - codon 70 - within the conserved CD225 domain of IFITMs. Mutation of this residue in microbat IFITM3 impairs restriction of four different virus families that enter cells via endosomes. This mutant shows altered subcellular localization and reduced S-palmitoylation, a phenotype copied by mutation of conserved cysteine residues in microbat IFITM3. Furthermore, we show that microbat IFITM3 is S-palmitoylated on cysteine residues C71, C72 and C105, mutation of each cysteine residue individually impairs virus restriction, and a triple C71-C72-C105 mutant loses all restriction, concomitant with subcellular re-localization of microbat IFITM3 to Golgi-associated sites. Thus, we propose that S-palmitoylation is critical for Chiropteran IFITM3 function and identify a key molecular determinant of IFITM3 S-palmitoylation.",2019-08-16,"Benfield, C. T. O.; Mazzon, M.; Tate, E.; Marsh, M.; Weston, S.; Mackenzie, F.; Holmes, E. C.; Kellam, P.; Teo, B. H.; Ritzefeld, M.; Smith, S.",,,,True
fd8d54106cd0cc2d09b1fda70f668736b5d0bd5c,biorxiv,"Evidence for influenza B virus hemagglutinin adaptation to the human host: high cleavability, acid-stability and preference for cool temperature",doi.org/10.1101/736678,,,See https://www.biorxiv.org/about-biorxiv,"Influenza A virus (IAV) and influenza B virus (IBV) cause yearly epidemics with significant morbidity and mortality. When zoonotic IAVs enter the human population, the viral hemagglutinin (HA) requires adaptation to achieve sustained virus transmission. In contrast, IBV has been circulating in humans, its only host, for a long period of time. Whether this entailed adaptation of IBV HA to the human airways is unknown. To address this question, we compared seasonal IAV (A/H1N1 and A/H3N2) and IBV viruses (B/Victoria and B/Yamagata lineage) with regard to host-dependent activity of HA as the mediator of membrane fusion during viral entry. We first investigated proteolytic activation of HA, by covering all type II transmembrane serine protease (TTSP) and kallikrein enzymes, many of which proved present in human respiratory epithelium. Compared to IAV, the IBV HA0 precursor is cleaved by a broader panel of TTSPs and activated with much higher efficiency. Accordingly, knockdown of a single protease, TMPRSS2, was sufficient to abrogate spread of IAV but not IBV in human respiratory epithelial cells. Second, the HA fusion pH proved similar for IBV and human-adapted IAVs (one exception being HA of 1918 IAV). Third, IBV HA exhibited higher expression at 33{degrees}C, a temperature required for membrane fusion by B/Victoria HA. This indicates pronounced adaptation of IBV HA to the mildly acidic pH and cooler temperature of human upper airways. These distinct and intrinsic features of IBV HA are compatible with extensive host-adaptation during prolonged circulation of this respiratory virus in the human population.\n\nImportanceInfluenza epidemics are caused by influenza A (IAV) and influenza B (IBV) viruses. IBV causes substantial disease, however it is far less studied than IAV. While IAV originates from animal reservoirs, IBV circulates in humans only. Virus spread requires that the viral hemagglutinin (HA) is active and sufficiently stable in human airways. We here resolve how these mechanisms differ between IBV and IAV. Whereas human IAVs rely on one particular protease for HA activation, this is not the case for IBV. Superior activation of IBV by several proteases should enhance shedding of infectious particles. IBV HA exhibits acid-stability and a preference for 33{degrees}C, indicating pronounced adaptation to the human upper airways, where the pH is mildly acidic and a cooler temperature exists. These adaptive features are rationalized by the long existence of IBV in humans, and may have broader relevance for understanding the biology and evolution of respiratory viruses.",2019-08-23,"Laporte, M.; Stevaert, A.; Raeymaekers, V.; Boogaerts, T.; Nehlmeier, I.; Chiu, W.; Benkheil, M.; Vanaudenaerde, B.; Pöhlmann, S.; Naesens, L. M.",,,,True
c08c3b98a956287a6eaf99f6d90969d7dd1410d1,biorxiv,The deubiquitinating activity of Middle East respiratory syndrome coronavirus papain-like protease delays the innate immune response and enhances virulence in a mouse model,doi.org/10.1101/751578,,,See https://www.biorxiv.org/about-biorxiv,"AbstractMiddle East respiratory syndrome coronavirus (MERS-CoV) continues to cause zoonotic infections and serious disease, primarily in the Arabian Peninsula, due to repeated spill-over from dromedary camels and subsequent nosocomial transmission. Approved MERS vaccines for use in animals or humans are not currently available. MERS-CoV replication requires the virus-encoded papain-like protease (PLpro) to cleave multiple sites in the viral replicase polyproteins, thereby releasing functional non-structural proteins. Additionally, PLpro is a deubiquitinating enzyme (DUB) that can remove ubiquitin(-like) moieties from substrates, presumably to counteract host antiviral responses. In previous work, we determined the crystal structure of MERS-CoV PLpro in complex with ubiquitin, facilitating the design of PLpro mutations that impair DUB activity without affecting viral polyprotein cleavage. Here, we introduced these DUB-inactivating mutations into the viral genome and examined their impact on MERS-CoV infection both in cell culture and in a lethal mouse model. Although overall replication of DUB-negative and wild-type (wt) recombinant MERS-CoV was comparable in multiple cell lines, infection with DUB-negative virus markedly increased mRNA levels for interferon (IFN)-{beta} and IFN-stimulated genes. Moreover, compared to a wt virus infection, the survival rate was significantly increased when DUB-negative MERS-CoV was used to infect transgenic mice expressing a human MERS-CoV receptor. Interestingly, DUB-negative and wt MERS-CoV replicated to the same titers in lungs of infected mice, but the DUB-negative virus was cleared faster, likely due to the observed accelerated and better-regulated innate immune responses, in contrast to delayed and subsequently excessive responses in wt virus-infected mice. This study provides the first direct evidence that the DUB activity of a coronaviral protease contributes to innate immune evasion and can profoundly enhance virulence in an animal model. Thus, reduction or removal of the innate immune-suppressive DUB activity of PLpros is a promising strategy for coronavirus attenuation in the context of rational vaccine development.\n\nAuthor SummaryAlthough zoonotic coronaviruses such as Middle East respiratory coronavirus (MERS-CoV) have pandemic potential, therapeutics and vaccines that counteract this public health threat are not currently available. Coronaviruses typically employ multiple strategies to evade the hosts innate immune response, which may enhance clinical disease and/or reduce the efficacy of modified live vaccines. The MERS-CoV-encoded papain-like protease (PLpro) is not only crucial for the expression of functional replicase proteins, but has also been postulated to antagonize ubiquitination-dependent steps during the activation of the innate immune response. Here, we report the generation of engineered MERS-CoVs mutants in which PLpros deubiquitinating (DUB) activity was specifically disrupted without affecting virus viability. In this manner, we could demonstrate that the DUB activity of PLpro suppresses the interferon response in MERS-CoV-infected cells. Strikingly, in the lungs of mice infected with DUB-negative MERS-CoV, innate immune responses were induced at an earlier stage of infection than in wt virus-infected mice. This group also showed a clearly increased survival, indicating that the DUB activity is an important MERS-CoV virulence factor. This proof-of-concept study establishes that the engineering of DUB-negative coronaviruses, which elicit a more effective immune response in the host, is a viable strategy for vaccine development.",2019-08-29,"Knaap, R.; Fernandez-Delgado, R.; Dalebout, T. J.; Oreshkova, N.; Bredenbeek, P. J.; Enjuanes, L.; Sola, I.; Snijder, E. J.; Kikkert, M.",,,,True
ce97f5b8be9e2d7eeb169762fc07a08bacb3e8cf,biorxiv,Identification of a Novel Base J Binding Protein Complex Involved in RNA Polymerase II Transcription Termination in Trypanosomes,doi.org/10.1101/753004,,,See https://www.biorxiv.org/about-biorxiv,"Base J, {beta}-D-glucosyl-hydroxymethyluracil, is a modification of thymine DNA base involved in RNA Polymerase (Pol) II transcription termination in kinetoplastid protozoa. Little is understood regarding how specific thymine residues are targeted for J-modification or the mechanism of J regulated transcription termination. To identify proteins involved in J-synthesis, we expressed a tagged version of the J-glucosyltransferase (JGT) in Leishmania tarentolae, and identified four co-purified proteins by mass spectrometry: protein phosphatase (PP1), a homolog of Wdr82, a potential PP1 regulatory protein (PNUTS) and a protein containing a J-DNA binding domain (named JBP3). Gel shift studies indicate JBP3 is a J-DNA binding protein. Reciprocal tagging, co-IP and sucrose gradient analyses indicate PP1, JGT, JBP3, Wdr82 and PNUTS form a multimeric complex in kinetoplastids, similar to the mammalian PTW/PP1 complex involved in transcription termination via PP1 mediated dephosphorylation of Pol II. Using RNAi and analysis of Pol II termination by RNA-seq and RT-PCR, we demonstrate that ablation of PNUTS, JBP3 and Wdr82 lead to defects in Pol II termination at the 3-end of polycistronic gene arrays in Trypanosoma brucei. Mutants also contain increased antisense RNA levels upstream of promoters, suggesting an additional role of the complex in regulating termination of bi-directional transcription. In addition, PNUTS loss causes derepression of silent Variant Surface Glycoprotein genes important for host immune evasion. Our results provide the first direct mechanistic link between base J and regulation of Pol II termination and suggest a novel molecular model for the role of the CTD of Pol II in terminating polycistronic transcription in trypanosomatids.\n\nAuthor SummaryTrypanosoma brucei is an early-diverged parasitic protozoan that causes African sleeping sickness in humans. The genome of T. brucei is organized into polycistronic gene clusters that contain multiple genes that are co-transcribed from a single promoter. We have recently described the presence of a modified DNA base J and variant of histone H3 (H3.V) at transcription termination sites within gene clusters where the loss of base J and H3.V leads to read-through transcription and the expression of downstream genes. We now identify a novel stable multimeric complex containing a J binding protein (JBP3), base J glucosyltransferase (JGT), PP1 phosphatase, PP1 interactive-regulatory protein (PNUTS) and Wdr82, which we refer to as PJW/PP1. A similar complex (PTW/PP1) has been shown to be involved in Pol II termination in humans and yeast. We demonstrate that PNUTS, JBP3 and Wdr82 mutants lead to read-through transcription in T. brucei. Our data suggest the PJW/PP1 complex regulates termination by recruitment to termination sites via JBP3-base J interactions and dephosphorylation of specific proteins (including Pol II and termination factors) by PP1. These findings significantly expand our understanding of mechanisms underlying transcription termination in eukaryotes, including divergent organisms that utilize polycistronic transcription and novel epigenetic marks such as base J and H3.V. The studies also provide the first direct mechanistic link between J modification of DNA at termination sites and regulated Pol II termination and gene expression in kinetoplastids.",2019-08-30,"Sabatini, R.; Kieft, R.; Zhang, Y.; Marand, A.; Moran, J.; Bridger, R.; Wells, L.; Schmitz, R. J.",,,,True
b0746b57a6c8f3cd9e52a27b0d708d069134b502,biorxiv,Bat coronavirus phylogeography in the western Indian Ocean,doi.org/10.1101/742866,,,See https://www.biorxiv.org/about-biorxiv,"Bats are important reservoirs of zoonotic pathogens, including coronaviruses (CoVs). The Western Indian Ocean (WIO) islands are a biodiversity hotspot with more than 50 bat species. Here we tested 1,099 bats belonging to 39 species from Mozambique, Madagascar, Mauritius, Mayotte, Reunion Island and Seychelles. Based on molecular screening and partial sequencing of the RNA-dependent RNA polymerase gene, a total of 88 bats (8.0% {+/-} 1.6%) tested positive for bat-borne coronaviruses (CoVs), with higher prevalence in Mozambican bats (19.6% {+/-} 4.7%) as compared to those sampled on islands (4.2% {+/-} 1.2%). Phylogenetic analyses revealed that a large diversity of - and {beta}-CoVs are maintained in bat populations of the WIO, some being genetically related to human CoVs (e.g. NL63, MERS). Finally, we found a strong signal of co-evolution between CoVs and their bat host species with limited evidence for host-switching, except for bat species sharing day roost sites.",2019-09-04,"Joffrin, L.; Goodman, S. M.; Wilkinson, D. A.; Ramasindrazana, B.; Lagadec, E.; Gomard, Y.; Le Minter, G.; Dos Santos, A.; Schoeman, M. C.; Sookhareea, R.; Tortosa, P.; Julienne, S.; Gudo, E.; Mavingui, P.; Lebarbenchon, C.",,,,True
fccf6791aac676cf26c0be7745e217f9b8d6336c,biorxiv,Antipsychotic behavioral phenotypes in the mouse Collaborative Cross recombinant inbred inter-crosses (RIX),doi.org/10.1101/761353,,,See https://www.biorxiv.org/about-biorxiv,"Schizophrenia is an idiopathic disorder that affects approximately 1% of the human population, and presents with persistent delusions, hallucinations, and disorganized behaviors. Antipsychotics are the standard pharmacological treatment for schizophrenia, but are frequently discontinued by patients due to inefficacy and/or side effects. Chronic treatment with the typical antipsychotic haloperidol causes tardive dyskinesia (TD), which manifests as involuntary and often irreversible orofacial movements in around 30% of patients. Mice treated with haloperidol develop many of the features of TD, including jaw tremors, tongue protrusions, and vacuous chewing movements (VCMs). In this study, we used genetically diverse Collaborative Cross (CC) recombinant inbred inter-cross (RIX) mice to elucidate the genetic basis of antipsychotic-induced adverse drug reactions (ADRs). We performed a battery of behavioral tests in 840 mice from 73 RIX lines (derived from 62 CC strains) treated with haloperidol or placebo in order to monitor the development of ADRs. We used linear mixed models to test for strain and treatment effects. We observed highly significant strain effects for almost all behavioral measurements investigated (p<0.001). Further, we observed strong strain-by-treatment interactions for most phenotypes, particularly for changes in distance traveled, vertical activity, and extrapyramidal symptoms (EPS). Estimates of overall heritability ranged from 0.21 (change in body weight) to 0.4 (VCMs and change in distance traveled) while the portion attributable to the interactions of treatment and strain ranged from 0.01 (for change in body weight) to 0.15 (for change in EPS). Interestingly, close to 30% of RIX mice exhibited VCMs, a sensitivity to haloperidol exposure, approximately similar to the rate of TD in humans chronically exposed to haloperidol. Understanding the genetic basis for the susceptibility to antipsychotic ADRs may be possible in mouse, and extrapolation to humans could lead to safer therapeutic approaches for schizophrenia.",2019-09-10,"Giusti-Rodriguez, P.; Xenakis, J.; Crowley, J. J.; Nonneman, R. J.; DeCristo, D. M.; Ryan, A.; Quackenbush, C. R.; Miller, D. R.; Shaw, G. D.; Zhabotynsky, V.; Sullivan, P.; Pardo-Manuel de Villena, F.; Zou, F.",,,,True
82c1bf108f88d4ec2b4e68106d9531f1c8b45a5c,biorxiv,A combined RNA-seq and whole genome sequencing approach for identification of non-coding pathogenic variants in single families.,doi.org/10.1101/766717,,,See https://www.biorxiv.org/about-biorxiv,"Inherited retinal degenerations (IRDs) are at the focus of current genetic therapeutic advancements. For a genetic treatment such as gene therapy to be successful an accurate genetic diagnostic is required. Genetic diagnostics relies on the assessment of the probability that a given DNA variant is pathogenic. Non-coding variants present a unique challenge for such assessments as compared to coding variants. For one, non-coding variants are present at much higher number in the genome than coding variants. In addition, our understanding of the rules that govern the non-coding regions of the genome is less complete than our understanding of the coding regions. Methods that allow for both the identification of candidate non-coding pathogenic variants and their functional validation may help overcome these caveats allowing for a greater number of patients to benefit from advancements in genetic therapeutics. We present here an unbiased approach combining whole genome sequencing (WGS) with patient induced pluripotent stem cell (iPSC) derived retinal organoids (ROs) transcriptome analysis. With this approach we identified and functionally validated a novel pathogenic non-coding variant in a small family with a previously unresolved genetic diagnosis.",2019-09-12,"Bronstein, R.; Capowski, E. E.; Mehrotra, S.; Jansen, A. D.; Navarro-Gomez, D.; Maher, M.; Place, E.; Sangermano, R.; Bujakowska, K. M.; Gamm, D. M.; Pierce, E. A.",,,,True
3fac0b7a9917984764a77f7fcb327e820e770d1b,biorxiv,Diversity of Archaea Domain in Cuatro Cienegas Basin: Archaean Domes.,doi.org/10.1101/766709,,,See https://www.biorxiv.org/about-biorxiv,"Herein we describe the Archaea diversity in a shallow pond in the Cuatro Cienegas Basin (CCB), Northeast Mexico, with fluctuating hypersaline conditions containing elastic microbial mats that can form small domes where their anoxic inside reminds us of the characteristics of the Archaean Eon, rich in methane and sulfur gases; thus, we named this site the Archaean Domes (AD). These domes only form after heavy rains that are rare in the Chihuahuan desert. CCB is a unique oasis with hundreds of ponds, containing endemic species of animals, plants and highly diverse and unique microbial communities, despite its very biased stoichiometry, due mostly to extreme low phosphorus content (soils, water columns and sediments). This extreme oligotrophy has favored survival of ancestral microorganisms. Whole metagenome sequencing approach was performed for this unusual site in three different seasons to assess the extent of the Archaea biodiversity, with a focus on extremophiles, since members of the Archaea had been underrepresented in different study sites within the oasis. We found a highly diverse Archaea community compassing [~]5% of the metagenomes. The archaeal portion in all three metagenomes maintained its abundance and most of the strains showed to form a resilient core during three seasonal samplings (2016-2017), despite environmental fluctuations. However, relative abundances of all 230 archaeal OTUs (defined using a 97% cutoff) were low enough (<0.1%) to be considered part of the rare biosphere. AD finding and their description within CCB confirms that this particular pond is the most diverse for Archaea that we are aware of and opens new paths for understanding the forces that once drove and keep shaping microbial community assemblage.",2019-09-12,"Medina-Chavez, N. O.; Viladomat-Jasso, M.; Olmedo, G.; Eguiarte, L. E.; Souza, V. O.; DE LA TORRE-ZAVALA, S.",,,,True
ec223563f366aa8ed21ec84d1b0d21a911362cfa,biorxiv,RNA-dependent RNA polymerase speed and fidelity are not the only determinants of the mechanism or efficiency of recombination.,doi.org/10.1101/769224,,,See https://www.biorxiv.org/about-biorxiv,"Using the RNA-dependent RNA polymerase (RdRp) from poliovirus (PV) as our model system, we have shown that Lys-359 in motif-D functions as a general acid in the mechanism of nucleotidyl transfer. A K359H (KH) RdRp derivative is slow and faithful relative to wild-type enzyme. In the context of the virus, RdRp-coding sequence evolves, selecting for the following substitutions: I331F (IF, motif-C) and P356S (PS, motif-D). We have evaluated IF-KH, PS-KH, and IF-PS-KH viruses and enzymes. The speed and fidelity of each double mutant are equivalent. Each exhibits a unique recombination phenotype, with IF-KH being competent for copy-choice recombination and PS-KH being competent for forced-copy-choice recombination. Although the IF-PS-KH RdRp exhibits biochemical properties within twofold of wild type, the virus is impaired substantially for recombination in cells. We conclude that there are biochemical properties of the RdRp in addition to speed and fidelity that determine the mechanism and efficiency of recombination. The interwoven nature of speed, fidelity, the undefined property suggested here, and recombination makes it impossible to attribute a single property of the RdRp to fitness. However, the derivatives described here may permit elucidation of the importance of recombination on the fitness of the viral population in a background of constant polymerase speed and fidelity.\n\nSignificanceThe availability of a \""universal\"" method to create attenuated viruses for use as vaccine strains would permit a rapid response to outbreaks of newly emerging viruses. Targeting RdRp fidelity has emerged as such a universal approach. However, because polymerase fidelity and speed are inextricably linked, the effort to attribute the attenuated phenotype to a single biochemical property of the RdRp may be futile. Here, we show that this circumstance is even more complex. We provide evidence for the existence of a biochemical parameter that combines with fidelity and speed to govern the mechanism and/or efficiency of recombination. We conclude that the field will be served best by continued emphasis on discovery of manipulatable functions of the RdRp instead of debating the importance of individual properties.",2019-09-14,"Kim, H.; Ellis, V. D.; Woodman, A.; Zhao, Y.; Arnold, J.; Cameron, C.",,,,True
f863247dc84916a96448088399badefd09d54fb8,biorxiv,Trypsin treatment unlocks barrier for zoonotic coronaviruses infection,doi.org/10.1101/768663,,,See https://www.biorxiv.org/about-biorxiv,"Traditionally, the emergence of coronaviruses (CoVs) has been attributed to a gain in receptor binding in a new host. Our previous work with SARS-like viruses argued that bats already harbor CoVs with the ability to infect humans without adaptation. These results suggested that additional barriers limit the emergence of zoonotic CoV. In this work, we describe overcoming host restriction of two MERS-like bat CoVs using exogenous protease treatment. We found that the spike protein of PDF2180-CoV, a MERS-like virus found in a Ugandan bat, could mediate infection of Vero and human cells in the presence of exogenous trypsin. We subsequently show that the bat virus spike can mediate infection of human gut cells, but is unable to infect human lung cells. Using receptor-blocking antibodies, we show that infection with the PDF2180 spike does not require MERS-CoV receptor DPP4 and antibodies developed against the MERS spike receptor-binding domain and S2 portion are ineffective in neutralizing the PDF2180 chimera. Finally, we found that addition of exogenous trypsin also rescues replication of HKU5-CoV, a second MERS-like group 2c CoV. Together, these results indicate that proteolytic cleavage of the spike, not receptor binding, is the primary infection barrier for these two group 2c CoVs. Coupled with receptor binding, proteolytic activation offers a new parameter to evaluate emergence potential of CoVs and offer a means to recover previously unrecoverable zoonotic CoV strains.\n\nImportanceOverall, our studies demonstrate that proteolytic cleavage is the primary barrier to infection for a subset of zoonotic coronaviruses. Moving forward, the results argue that both receptor binding and proteolytic cleavage of the spike are critical factors that must be considered for evaluating the emergence potential and risk posed by zoonotic coronaviruses. In addition, the findings also offer a novel means to recover previously uncultivable zoonotic coronavirus strains and argue that other tissues, including the digestive tract, could be a site for future coronavirus emergence events in humans.",2019-09-16,"Menachery, V. D.; Dinnon, K.; Yount, B.; McAnarney, E. T.; Gralinski, L.; Hale, A. E.; Graham, R.; Scobey, T. D.; Anthony, S. J.; Wang, L.; Graham, B. S.; Randell, S. H.; Lipkin, W. I.; Baric, R. S.",,,,True
37afeaa38d66b8097cc7637bf62ac7d142e6b362,biorxiv,Evolutionary origins of epidemic potential among human RNA viruses,doi.org/10.1101/771394,,,See https://www.biorxiv.org/about-biorxiv,"To have epidemic potential, a pathogen must be able to spread in human populations, but of human-infective RNA viruses only a minority can do so. We investigated the evolution of human transmissibility through parallel analyses of 1755 virus genome sequences from 39 RNA virus genera. We identified 57 lineages containing human-transmissible species and estimated that at least 74% of these lineages have evolved directly from non-human viruses in other mammals or birds, a public health threat recently designated \""Disease X\"". Human-transmissible viruses rarely evolve from virus lineages that can infect but not transmit between humans. This result cautions against focussing surveillance and mitigation efforts narrowly on currently known human-infective virus lineages and supports calls for a better understanding of RNA virus diversity in non-human hosts.",2019-09-18,"Lu, L.; Brierley, L.; Robertson, G.; Zhang, F.; Lycett, S. J.; Smith, D.; Chase-Topping, M.; Simmonds, P.; Woolhouse, M. E. J.",,,,True
4f1c22de2d2e0b3f2a12bf2a557d429d3ae31a5b,biorxiv,Astrovirus in Reunion Free-tailed Bat (Mormopterus francoismoutoui),doi.org/10.1101/774224,,,See https://www.biorxiv.org/about-biorxiv,"Astroviruses (AstVs) are RNA viruses responsible for infection of a large diversity of avian and mammalian species, including bats, livestock, and humans. We investigated AstV infection in a free-tailed bat species, Mormopterus francoismoutoui, endemic to Reunion Island. A total of 190 guano samples were collected in a maternity colony during 19 different sampling sessions, between June 2016 and June 2017. Biological material was tested for the presence of the AstV RNA-dependent RNA-polymerase (RdRp) gene with a pan-AstV semi-nested polymerase chain reaction assay. In total, 15 guano samples (7.9%) tested positive, with high genetic diversity of the partial RdRp gene sequences among positive samples. A phylogenetic analysis further revealed that the detected viruses were genetically related to AstVs reported in reptiles, dogs, and pigs, but did not cluster with AstVs commonly found in bats. Although more investigation need to be conducted to assess the level of infected bats in the studied population, our findings suggest that Reunion free-tailed bats are exposed to AstV, and that cross-species transmission may occur with other hosts sharing the same habitat.",2019-09-19,"Joffrin, L.; Hoarau, A. O. G.; Lagadec, E.; Mavingui, P.; Lebarbenchon, C.",,,,True
73a954bbd21a08cf0a662b37f1f97989285969c4,biorxiv,Prodrug defiance reveals logic-based strategies for treating bacterial resistance,doi.org/10.1101/556951,,,See https://www.biorxiv.org/about-biorxiv,"Classifying the mechanisms of antibiotic failure has led to the development of new treatment strategies for killing bacteria. Among the currently described mechanisms, which include resistance, persistence and tolerance, we propose bacterial defiance as a form of antibiotic failure specific to prodrugs. As a prototypic model of a bacteria-activated prodrug, we construct cationic antimicrobial peptides (AMP), which are charge neutralized until activated by a bacterial protease. This construct successfully eliminated the vast majority of bacteria populations, while localizing activity to bacterial membranes and maintaining low active drug concentration. However, we observed defiant bacteria populations, which survive in the presence of identical drug concentration and exposure time. Using a multi-rate kinetic feedback model, we show that bacteria switch between susceptibility and defiance under clinically relevant environmental (e.g., hyperthermia) and genetic (e.g., downregulated protease expression) conditions. From this model, we derive a dimensionless quantity (Bacterial Advantage Heuristic, BAH) - representing the balance between bacterial proliferation and prodrug activation - that perfectly classifies bacteria as defiant or susceptible across a broad range of conditions. To apply this concept to other classes of prodrugs, we expand this model to include both linear and nonlinear terms and use general pharmacokinetic parameters (e.g., half-life, EC50, etc.). Taken together, this model reveals an analogous dimensionless quantity (General Advantage Key, GAK), which can applied to prodrugs with different activation mechanisms. We envision that these studies will enable the development of more effective prodrugs to combat antibiotic resistance.",2019-09-23,"Holt, B. A.; Curro, I.; Kwong, G. A.",,,,True
ab1692d56f32fdb0922e5f323f6ca385fb1e0808,biorxiv,First evidence of host range expansion in virophages and its potential impact on giant viruses and host cells,doi.org/10.1101/780841,,,See https://www.biorxiv.org/about-biorxiv,"Virophages are satellite-like double stranded DNA viruses whose replication requires the presence of two biological entities, a giant virus and a protist. In this report, we present the first evidence of host range expansion in a virophage. We demonstrated that the Guarani virophage was able to spontaneously expand its viral host range to replicate with two novel giant viruses that were previously nonpermissive to this virophage. We were able to characterize a potential genetic determinant of this cross-species infection. We then highlighted the relevant impact of this host adaptation on giant viruses and protists by demonstrating that coinfection with the mutant virophage abolishes giant virus production and rescues the host cell population from lysis. The results of our study help to elucidate the parasitic lifestyle of virophages and their interactions with giant viruses and protists.",2019-09-24,"Mougari, S.; Chelkha, N.; Sahmi-Bounsiar, D.; Di Pinto, F.; Colson, P.; Abrahao, J.; La Scola, B.",,,,True
ce16fdcdc9f5932ac2e66646317a33f142ee1eb6,biorxiv,Herpesvirus infection reduces Pol II occupancy of host promoters but spares viral promoters,doi.org/10.1101/585984,,,See https://www.biorxiv.org/about-biorxiv,"In mammalian cells, widespread acceleration of cytoplasmic mRNA degradation is linked to impaired RNA polymerase II (Pol II) transcription. This mRNA decay-induced transcriptional repression occurs during infection with gammaherpesviruses including Kaposis sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV68), which encode an mRNA endonuclease that initiates widespread RNA decay. Here, we show that MHV68-induced mRNA decay leads to a genome-wide reduction of Pol II occupancy at mammalian promoters. Viral genes, despite the fact that they require Pol II for transcription, escape this transcriptional repression. Protection is not governed by viral promoter sequences; instead, location on the viral genome is both necessary and sufficient to escape the transcriptional repression effects of mRNA decay. We hypothesize that the ability to escape from transcriptional repression is linked to the localization of viral DNA in replication compartments, providing a means for these viruses to counteract decay-induced viral transcript loss.",2019-09-24,"Hartenian, E.; Glaunsinger, B.",,,,True
d5efae48a9bbfccac8d9e6c1a80c8c605d80ee21,biorxiv,Influence of different glycoproteins and of the virion core on SERINC5 antiviral activity,doi.org/10.1101/780577,,,See https://www.biorxiv.org/about-biorxiv,"Host plasma membrane protein SERINC5 is incorporated into budding retrovirus particles where it blocks subsequent entry into susceptible target cells. Three accessory proteins encoded by diverse retroviruses, HIV-1 Nef, EIAV S2, and MLV Glycogag, each independently disrupt SERINC5 antiviral activity, by redirecting SERINC5 from the site of virion assembly on the plasma membrane to an internal RAB7+ endosomal compartment. Pseudotyping retroviruses with particular glycoproteins, e.g., the vesicular stomatitis glycoprotein (VSV G), renders the infectivity of particles resistant to inhibition by virion-associated SERINC5. To better understand viral determinants for SERINC5-sensitivity, the effect of SERINC5 was assessed using HIV-1, MLV, and M-PMV virion cores, pseudotyped with glycoproteins from Arenavirus, Coronavirus, Filovirus, Rhabdovirus, Paramyxovirus, and Orthomyxovirus genera. Infectivity of particles, pseudotyped with HIV-1, amphotropic-MLV, or influenza virus glycoproteins, was decreased by SERINC5, whether the core was provided by HIV-1, MLV, or M-PMV. Particles generated by all three cores, and pseudotyped with glycoproteins from either avian leukosis virus-A, human endogenous retrovirus K (HERV-K), ecotropic-MLV, HTLV-1, Measles morbillivirus, lymphocytic choriomeningitis mammarenavirus (LCMV), Marburg virus, Ebola virus, severe acute respiratory syndrome-related coronavirus (SARS-CoV), or VSV, were insensitive to SERINC5. In contrast, particles pseudotyped with M-PMV, RD114, or rabies virus (RABV) glycoproteins were sensitive to SERINC5, but only with particular retroviral cores. Resistance to SERINC5 by particular glycoproteins did not correlate with reduced SERINC5 incorporation into particles or with the route of viral entry. These findings indicate that some non-retroviruses may be sensitive to SERINC5 and that, in addition to the viral glycoprotein, the retroviral core influences sensitivity to SERINC5.\n\nIMPORTANCEThe importance of SERINC5 for inhibition of retroviruses is underscored by convergent evolution among three non-monophyletic retroviruses, each of which encodes a structurally unrelated SERINC5 inhibitor. One of these retroviruses causes tumors in mice, a second anemia in horses, and a third causes AIDS. SERINC5 is incorporated into retrovirus particles where it blocks entry into target cells, via a mechanism that is dependent on the viral glycoprotein. Here we demonstrate that retroviruses pseudotyped with glycoproteins from several non-retroviruses are also inhibited by SERINC5, suggesting that enveloped viruses other than retroviruses may also be inhibited by SERINC5. Additionally, we found that sensitivity to SERINC5 is determined by the retrovirus core, as well as by the glycoprotein. By better understanding how SERINC5 inhibits viruses we hope to extend fundamental understanding of virus replication and of the native role of SERINC5 in cells, and perhaps to advance the development of new antiviral strategies.",2019-09-24,"Diehl, W. E.; Guney, M. H.; Kyawe, P. P.; White, J. M.; Pizzato, M.; Luban, J.",,,,True
3c14c4c3a176c86833794029e787ce460c9d89dd,biorxiv,A comprehensive annotation and differential expression analysis of short and long non-coding RNAs in 16 bat genomes,doi.org/10.1101/738526,,,See https://www.biorxiv.org/about-biorxiv,"Although bats are increasingly becoming the focus of scientific studies due to their unique properties, these exceptional animals are still among the least studied mammals. Assembly quality and completeness of bat genomes vary a lot and especially non-coding RNA (ncRNA) annotations are incomplete or simply missing. Accordingly, standard bioinformatics pipelines for gene expression analysis often ignore ncRNAs such as microRNAs or long antisense RNAs. The main cause of this problem is the use of incomplete genome annotations. We present a complete screening for ncRNAs within 16 bat genomes. NcRNAs affect a remarkable variety of vital biological functions, including gene expression regulation, RNA processing, RNA interference and, as recently described, regulatory processes in viral infections. Within all investigated bat assemblies we annotated 667 ncRNA families including 162 snoRNAs and 193 miRNAs as well as rRNAs, tRNAs, several snRNAs and IncRNAs, and other structural ncRNA elements. We validated our ncRNA candidates by six RNA-Seq data sets and show significant expression patterns that have never been described before in a bat species on such a large scale. Our annotations will be usable as a resource (Electronic Supplement) for deeper studying of bat evolution, ncRNAs repertoire, gene expression and regulation, ecology, and important host-virus interactions.  Supplementary informationis available at rna.uni-jena.de/supplements/bats, the Open Science Framework (doi.org/10.17605/OSF.IO/4CMDN), and GitHub (github.com/rnajena/bats_ncrna).",2019-09-25,"Mostajo Berrospi, N.; Lataretu, M.; Krautwurst, S.; Mock, F.; Desiro, D.; Lamkiewicz, K.; Collatz, M.; Schoen, A.; Weber, F.; Marz, M.; Hölzer, M.",,,,True
d1d6a474989c30c3c93ecc00f886125a384efb35,biorxiv,Temperature Dramatically Shapes Mosquito Gene Expression with Consequences for Mosquito-Zika Virus Interactions,doi.org/10.1101/783035,,,See https://www.biorxiv.org/about-biorxiv,"Vector-borne flaviviruses are emerging threats to human health. For successful transmission, the virus needs to efficiently enter mosquito cells, replicate within, and escape several tissue barriers while mosquitoes elicit major transcriptional responses to flavivirus infection. This process will not only be affected by the specific mosquito-pathogen pairing, but also variation in key environmental variables such as temperature. Thus far, few studies have examined the molecular responses triggered by temperature and how these responses modify infection outcomes despite substantial evidence showing strong relationships between temperature and transmission in a diversity of systems. To define the host transcriptional changes associated with temperature variation during the early infection process, we compared the transcriptome of mosquito midgut samples from mosquitoes exposed to Zika virus (ZIKV) and non-exposed mosquitoes housed at three different temperatures (20, 28, and 36{degrees}C). While the high temperature samples did not have significant changes from standard rearing conditions (28{degrees}C) 48 hr post-exposure, the transcriptome profile of mosquitoes housed at 20{degrees}C was dramatically different. The expression of genes most altered by the cooler temperature involved aspects of blood-meal digestion, ROS metabolism, and mosquito innate immunity. Further, we did not find significant differences in the viral RNA copy number between 24 and 48 hr post-exposure at 20{degrees}C, suggesting ZIKV replication is limited by cold-induced changes to the mosquito midgut environment. In ZIKV-exposed mosquitoes, vitellogenin, a lipid carrier protein, was the most up-regulated at 20{degrees}C. Our results provide a deeper understanding of the temperature-triggered transcriptional changes in Aedes aegypti and can be used to further define the molecular mechanisms driven by environmental temperature variation.\n\nContribution to the Field StatementA variety of methods for engineering refractory mosquitoes are currently being studied and show promise for disease control. Although considerable effort has been put into understanding the immune system of mosquitoes in response to infections, almost nothing is understood about environmental influences in regulating these responses. Here, we used RNA sequencing to study the effect of temperature on the mosquito transcriptome profile, as well as assess the changes in the immune response to ZIKV infection at three different temperatures. We found a remarkable effect of temperature on the transcriptome profile of mosquitoes exposed to cool conditions (20{degrees}C) after imbibing a blood meal, as well as accumulation of transcripts involved with different mechanisms associated with blood meal digestion, metabolism, and some components of the immune response in mosquitoes. Our results provide new insights in potential mechanisms that limit temperature-driven pathogen establishment and replication within the mosquito vector.",2019-09-26,"Ferreira, P.; Tesla, B.; Hor&aacutecio, E.; Nahum, L.; Brindley, M.; Mendes, T.; Murdock, C.",,,,False
c4dc1c0360d3fe9ceddc4650aea022f24d88cd99,biorxiv,Vaccination with single plasmid DNA encoding IL-12 and antigens of severe fever with thrombocytopenia syndrome virus elicits complete protection in IFNAR knockout mice,doi.org/10.1101/787879,,,See https://www.biorxiv.org/about-biorxiv,"Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by SFTS virus (SFTSV) infection. Despite a gradual increase of SFTS cases and high mortality in endemic regions, no specific viral therapy nor vaccine is available. Here, we developed a single recombinant plasmid DNA encoding SFTSV genes, Gn and Gc together with NP-NS fusion antigen, as a vaccine candidate. The viral antigens were fused with Fms-like tyrosine kinase-3 ligand (Flt3L) and IL-12 gene was incorporated into the plasmid to enhance cell-mediated immunity. Vaccination with the DNA provides complete protection of IFNAR KO mice upon lethal SFTSV challenge, whereas immunization with a plasmid without IL-12 gene resulted in partial protection. Since we failed to detect antibodies against surface glycoproteins, Gn and Gc, in the immunized mice, antigen-specific cellular immunity, as confirmed by enhanced antigen-specific T cell responses, might play major role in protection. Finally, we evaluated the degree of protective immunity provided by protein immunization of the individual glycoprotein, Gn or Gc. Although both protein antigens induced a significant level of neutralizing activity against SFTSV, Gn vaccination resulted in relatively higher neutralizing activity and better protection than Gc vaccination. However, both antigens failed to provide complete protection. Given that DNA vaccines have failed to induce sufficient immunogenicity in human trials when compared to protein vaccines, optimal combinations of DNA and protein elements, proper selection of target antigens, and incorporation of efficient adjuvant, need to be further investigated for SFTSV vaccine development.\n\nAuthor summarySevere fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infection endemic to East Asia including China, Korea, and Japan. Gradual rise of disease incidence and relatively high mortality have become a serious public health problem in the endemic countries. In this study, we developed a recombinant plasmid DNA encoding four antigens, Gn, Gc, NP, and NS, of SFTS virus (SFTSV) as a vaccine candidate. In order to enhance cell-mediated immunity, the viral antigens were fused with Flt3L and IL-2 gene was incorporated into the plasmid. Immunization with the DNA vaccine provides complete protection against lethal SFTSV infection in IFNAR KO mice. Antigen-specific T cell responses might play a major role in the protection since we observed enhanced T cell responses specific to the viral antigens but failed to detect neutralizing antibody in the immunized mice. When we immunized with either viral glycoprotein, Gn protein induced relatively higher neutralizing activity and better protection against SFTSV infection than Gc antigen, but neither generated complete protection. Therefore, an optimal combination of DNA and protein elements, as well as proper selection of target antigens, might be required to produce an effective SFTSV vaccine.",2019-09-30,"Kang, J.-G.; Jeon, K.; Choi, H.; Kim, Y.; Kim, H.-I.; Ro, H.-J.; Seo, Y. B.; Shin, J.; Chung, J.; Jeon, Y. K.; Kim, Y. S.; Lee, K. H.; Cho, N.-H.",,,,True
4f5901d41427c10d4dafdc6d3cef2dd20bba871a,biorxiv,Kin and group selection are both flawed but useful data analysis tools,doi.org/10.1101/742122,,,See https://www.biorxiv.org/about-biorxiv,"For understanding the evolution of social behavior in microbes, mathematical theory can aid empirical research but is often only used as a qualitative heuristic. How to properly formulate social evolution theory has also been contentious. Here we evaluate kin and multilevel selection theory as tools for analyzing microbial data. We reanalyze published datasets that share a common experimental design and evaluate these theories in terms of data visualization, statistical performance, biological interpretation, and quantitative comparison across systems. We find that the canonical formulations of both kin and multilevel selection are almost always poor analytical tools because they use statistical regressions that are poorly specified for the strong selection and nonadditive fitness effects common in microbial systems. Analyzing both individual and group fitness outcomes helps clarify the biology of selection. We also identify analytical practices in empirical research that suggest how theory might better handle the challenges of microbial data. A quantitative, data-driven approach thus shows how kin and multilevel selection theory both have substantial room for improvement as tools for understanding social evolution in all branches of life.",2019-10-01,"smith, j.; Inglis, R. F.",,,,True
78ab74f8133c0dfe8fb414c216350dd37f69b0bf,biorxiv,"A quantitative narrative on movement, disease and patch exploitation in nesting agent groups",doi.org/10.1101/791400,,,See https://www.biorxiv.org/about-biorxiv,"Animal relocation data has recently become considerably more ubiquitous, finely structured (collection frequencies measured in minutes) and co-variate rich (physiology of individuals, environmental and landscape information, and accelerometer data). To better understand the impacts of ecological interactions, individual movement and disease on global change ecology, including wildlife management and conservation, it is important to have simulators that will provide demographic, movement, and epidemiology null models against which to compare patterns observed in empirical systems. Such models may then be used to develop quantitative narratives that enhance our intuition and understanding of the relationship between population structure and generative processes: in essence, along with empirical and experimental narratives, quantitative narratives are used to advance ecological epistemology. Here we describe a simulator that accounts for the influence of consumer-resource interactions, existence of social groups anchored around a central location, territoriality, group-switching behavior, and disease dynamics on population size. We use this simulator to develop new and reinforce existing quantitative narratives and point out areas for future study.\n\nAuthor summaryThe health and viability of species are of considerable concern to all nature lovers. Population models are central to our efforts to assess the numerical and ecological status of species and threats posed by climate change. Models, however, are crude caricatures of complex ecological systems. So how do we construct reliable assessment models able to capture processes essential to predicating the impacts of global change on population viability without getting tied up in their vast complexities? We broach this question and demonstrate how models focusing at the level of the individual (i.e., agent-based models) are tools for developing robust, narratives to augment narratives arising purely from empirical data sources and experimental outcomes. We do this in the context of nesting social groups, foraging for food, while exhibiting territoriality and group-switching behavior; and, we evaluate the impact of disease on the viability of such populations.",2019-10-03,"Getz, W. M.; Salter, R.; Tallam, K.",,,,True
daf507bcd9337e05d4bdc3da73e05639837f2031,biorxiv,TLR5 participates in the TLR4 receptor complex and biases towards MyD88-dependent signaling in environmental lung injury,doi.org/10.1101/792705,,,See https://www.biorxiv.org/about-biorxiv,"Lung disease causes significant morbidity and mortality, and is exacerbated by environmental injury, e.g. through lipopolysaccharide (LPS) or ozone (O3). Toll-like receptors (TLRs) orchestrate immune responses to injury by recognizing pathogen- or danger-associated molecular patterns. TLR4, the prototypic receptor for LPS, also mediates inflammation after O3, triggered by endogenous hyaluronan. Regulation of TLR4 signaling is incompletely understood. TLR5, the flagellin receptor, is expressed in alveolar macrophages, and regulates immune responses to environmental injury. Using in vivo animal models of TLR4-mediated inflammations (LPS, O3, hyaluronan), we show that TLR5 impacts the in vivo response to LPS, hyaluronan and O3. We demonstrate that immune cells of human carriers of a dominant negative TLR5 allele have decreased inflammatory response to O3 exposure ex vivo and LPS exposure in vitro. Using primary murine macrophages, we find that TLR5 physically associates with TLR4 and biases TLR4 signaling towards the MyD88 pathway. Our results suggest an updated paradigm for TLR4/TLR5 signaling.",2019-10-03,"Hussain, S.; Johnson, C. C.; Sciurba, J.; Meng, X.; Stober, V. P.; Liu, C.; Cypher-Daly, J.; Bulek, K.; Qian, W.; Solis, A.; Sakamachi, Y.; Trempus, C.; Aloor, J. J.; Gowdy, K.; Foster, W. M.; Hollingsworth, J. W.; Tighe, R. M.; Li, X.; Fessler, M. B.; Garantziotis, S.",,,,True
0381d0a7aa87ad4fa38d609919f939b224b3a70b,biorxiv,Upstream translation initiation expands the coding capacity of segmented negative-strand RNA viruses,doi.org/10.1101/795815,,,See https://www.biorxiv.org/about-biorxiv,"Segmented negative-strand RNA viruses (sNSVs) include the influenza viruses, the bunyaviruses, and other major pathogens of humans, other animals and plants. The genomes of these viruses are extremely short. In response to this severe genetic constraint, sNSVs use a variety of strategies to maximise their coding potential. Because the eukaryotic hosts parasitized by sNSVs can regulate gene expression through low levels of translation initiation upstream of their canonical open reading frames (ORFs), we asked whether sNSVs could use upstream translation initiation to expand their own genetic repertoires. Consistent with this hypothesis, we showed that influenza A viruses (IAVs) and bunyaviruses were capable of upstream translation initiation. Using a combination of reporter assays and viral infections, we found that upstream translation in IAVs can initiate in two unusual ways: through non-AUG initiation in virally encoded  untranslated regions, and through the appropriation of an AUG-containing leader sequence from host mRNAs through viral cap-snatching, a process we termed  start-snatching. Finally, while upstream translation of cellular genes is mainly regulatory, for sNSVs it also has the potential to create novel viral gene products. If in frame with a viral ORF, this creates N-extensions of canonical viral proteins. If not, it allows the expression of cryptic overlapping ORFs, which we found were highly conserved in IAV and widely distributed in peribunyaviruses. Thus, by exploiting their hosts capacity for upstream translation initiation, sNSVs can expand still further the coding potential of their extremely compact RNA genomes.",2019-10-08,"Sloan, E.; Alenquer, M.; Chung, L.; Clohisey, S. M. R.; Dinan, A. M.; Gifford, R. J.; Gu, Q.; Irigoyen, N.; Jones, J. D.; van Knippenberg, I.; Rezelj, V. V.; Wang, B.; Wise, H.; Amorim, M.-J.; Baillie, J. K.; Brierley, I.; Digard, P.; Firth, A.; MacLeod, M. K.; Hutchinson, E.",,,,False
5f06ba54c9208857d92abfd16488c44217f8d726,biorxiv,Remote control of neural function by X-ray-induced scintillation,doi.org/10.1101/798702,,,See https://www.biorxiv.org/about-biorxiv,"Scintillators exhibit visible luminescence, called scintillation, when irradiated with X-rays. Given that X-rays penetrate through biological tissues, X-ray-induced scintillation would enable remote optogenetic control of neural functions at any depths in the brain. Here we show that a yellow-emitting inorganic scintillator, Ce-doped Gd3(Al,Ga)5O12 (Ce:GAGG), can effectively activate red-shifted excitatory and inhibitory opsins. Using these scintillator-opsin combinations, we successfully activated and inhibited midbrain dopamine neurons of freely moving mice by X-ray irradiation, producing bi-directional modulation of place preference behavior. The Ce:GAGG crystal was biocompatible and could be implanted for a long period without progressive neuroinflammatory responses. Neither brain injury nor behavioral dysfunction was acutely induced by radiation during the behavioral tests. Thus, X-ray-induced scintillation allows wireless control of cellular functions in living animals, expanding X-ray applications to functional studies of biology and medicine.",2019-10-09,"Matsubara, T.; Yanagida, T.; Kawaguchi, N.; Nakano, T.; Yoshimoto, J.; Tsunoda, S. P.; Horigane, S.-i.; Ueda, S.; Takemoto-Kimura, S.; Kandori, H.; Yamanaka, A.; Yamashita, T.",,,,True
f0f3f4ab41fdd2d12c3fa45dc53a17d7c58a4068,biorxiv,Saturation mutagenesis genome engineering of infective {Phi}X174 bacteriophage via unamplified oligo pools and golden gate assembly,doi.org/10.1101/798546,,,See https://www.biorxiv.org/about-biorxiv,"Here we present a novel protocol for the construction of saturation single-site--and massive multi-site--mutant libraries of a bacteriophage. We segmented the {Phi}X174 genome into 14 non-toxic and non-replicative fragments compatible with golden gate assembly. We next used nicking mutagenesis with oligonucleotides prepared from unamplified oligo pools with individual segments as templates to prepare near-comprehensive single-site mutagenesis libraries of genes encoding the F capsid protein (421 amino acids scanned) and G spike protein (172 amino acids scanned). Libraries possessed greater than 99% of all 11,860 programmed mutations. Golden Gate cloning was then used to assemble the complete {Phi}X174 mutant genome and generate libraries of infective viruses. This protocol will enable reverse genetics experiments for studying viral evolution and, with some modifications, can be applied for engineering of therapeutically relevant bacteriophages with larger genomes.",2019-10-09,"Faber, M. S.; Van Leuven, J. T.; Ederer, M. M.; Wilson, Z. L.; Sapozhnikov, Y.; Wichman, H. A.; Whitehead, T. A.; Miller, C. R.",,,,True
1a791c5c6543aca9391b77ae58b79d7ddf3c1f3c,biorxiv,The effects of modified sialic acids on mucus and erythrocytes on influenza A virus HA and NA functions,doi.org/10.1101/800300,,,See https://www.biorxiv.org/about-biorxiv,"Sialic acids (Sia) are the primary receptors for influenza viruses, and are widely displayed on cell surfaces and in secreted mucus. Sia may be present in variant forms that include O-acetyl modifications at C4, C7, C8, and C9 positions, and N-acetyl or N-glycolyl at C5. They can also vary in their linkages, including 2-3 or 2-6-linkages. Here, we analyzed the distribution of modified Sia in cells and tissues of wild-type mice, or in mice lacking cytidine 5-monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) enzyme that synthesizes N-glycolyl modifications (Neu5Gc). We also examined the variation of Sia forms on erythrocytes and saliva from different animals. To determine the effect of Sia modifications on influenza A virus (IAV) infection, we tested for effects on hemagglutinin (HA) binding and neuraminidase (NA) cleavage. We confirmed that 9-O-acetyl, 7,9-O-acetyl, 4-O-acetyl, and Neu5Gc modifications are widely but variably expressed in mouse tissues, with the highest levels detected in the respiratory and gastrointestinal tracts. Secreted mucins in saliva and surface proteins of erythrocytes showed a great degree of variability in display of modified Sia between different species. IAV HA from different virus strains showed consistently reduced binding to both Neu5Gc and O-acetyl modified Sia; however, while IAV NA were inhibited by Neu5Gc and O-acetyl modifications, there was significant variability between NA types. The modifications of Sia in mucus may therefore have potent effects on the functions of IAV, and may affect both pathogens and the normal flora of different mucosal sites.\n\nIMPORTANCESialic acids (Sia) are involved in many different cellular functions and are receptors for many pathogens. Sia come in many chemically modified forms but we lack a clear understanding of how they alter the interactions with microbes. Here we examine the expression of modified Sia in mouse tissues, on secreted mucus in saliva, and on erythrocytes, including those from IAV host species and animals used in IAV research. These Sia forms varied considerably between different animals, and their inhibitory effects on IAV NA and HA activities and on bacterial sialidases (neuraminidases) suggest a host-variable protective role in secreted mucus.",2019-10-10,"Barnard, K. N.; Alford-Lawrence, B. K.; Buchholz, D. W.; Wasik, B. R.; LaClair, J. R.; Yu, H.; Honce, R.; Ruhl, S.; Pajic, P.; Daugherity, E. K.; Chen, X.; Schultz-Cherry, S.; Aguilar, H. C.; Varki, A.; Parrish, C. R.",,,,True
c6083ef497ef3b5301404efe5519cfbd8cf82eb7,biorxiv,In silico identification of potential inhibitors against human 2’-5’-oligoadenylate synthetase (OAS) proteins,doi.org/10.1101/804716,,,See https://www.biorxiv.org/about-biorxiv,"As part of the type I IFN signaling, the 2-5- oligoadenylate synthetase (OAS) proteins have been involved in the progression of several non-viral diseases. Notably, OAS has been correlated with immune-modulatory functions that promote chronic inflammatory conditions, autoimmune disorders, cancer, and infectious diseases. In spite of this, OAS enzymes have been ignored as drug targets, and to date, there are no reports of compounds that can inhibit their activity. In this study, we have used homology modeling and virtual high-throughput screening to identify potential inhibitors of the human proteins OAS1, OAS2, and OAS3. Altogether, we have found 37 molecules that could exert a competitive inhibition in the ATP binding sites of OAS proteins, independently of the activation state of the enzyme. This latter characteristic, which might be crucial for a versatile inhibitor, was observed in compounds interacting with the residues Asp75, Asp77, Gln229, and Tyr230 in OAS1, and their equivalents in OAS2 and OAS3. Although there was little correlation between specific chemical fragments and particular interactions, intermolecular contacts with OAS catalytic triad and other critical amino acids were mainly promoted by heterocycles with {pi} electrons and hydrogen bond acceptors. In conclusion, this study provides a potential set of OAS inhibitors as well as valuable information for their design, development, and optimization.",2019-10-15,"Gonzalez Restrepo, K. J.; Moncada Giraldo, D. M.; Gutierrez, J. B.",,,,False
aa691effdd96a6e2bb0a401ab745b7158a8a13e1,biorxiv,Bayesian Evaluation of Temporal Signal in Measurably Evolving Populations,doi.org/10.1101/810697,,,See https://www.biorxiv.org/about-biorxiv,"Phylogenetic methods can use the sampling times of molecular sequence data to calibrate the molecular clock, enabling the estimation of substitution rates and time scales for rapidly evolving pathogens and data sets containing ancient DNA samples. A key aspect of such calibrations is whether a sufficient amount of molecular evolution has occurred over the sampling time window, that is, whether the data can be treated as being from a measurably evolving population. Here we investigate the performance of a fully Bayesian evaluation of temporal signal (BETS) in molecular sequence data. The method involves comparing the fit of two models: a model in which the data are accompanied by the actual (heterochronous) sampling times, and a model in which the samples are constrained to be contemporaneous (isochronous). We conduct extensive simulations under a range of conditions to demonstrate that BETS accurately classifies data sets according to whether they contain temporal signal or not, even when there is substantial among-lineage rate variation. We explore the behaviour of this classification in analyses of five data sets: modern samples of A/H1N1 influenza virus, the bacterium Bordetella pertussis, and coronaviruses from mammalian hosts, and ancient DNA data sets of Hepatitis B virus and of mitochondrial genomes of dog species. Our results indicate that BETS is an effective alternative to other measures of temporal signal. In particular, this method has the key advantage of allowing a coherent assessment of the entire model, including the molecular clock and tree prior which are essential aspects of Bayesian phylodynamic analyses.",2019-10-21,"Duchene, S.; Lemey, p.; Stadler, T.; Ho, S. Y.; Duchene, D. A.; Dhanasekaran, V.; Baele, G.",,,,False
315197247b230bab03786c197dc1fc795164c371,biorxiv,Long noncoding RNA AVAN promotes antiviral innate immunity by interacting with TRIM25 and enhancing the transcription of FOXO3a,doi.org/10.1101/623132,,,See https://www.biorxiv.org/about-biorxiv,"Accumulating evidence has shown that long noncoding RNAs (lncRNAs) are involved in several biological processes, including immune responses. However, the role of lncRNAs in antiviral innate immune responses remains largely unexplored. Here, we identify an uncharacterized human lncRNA from influenza A virus (IAV) patients, antivirus and activate neutrophil (AVAN), that is significantly up-regulated upon virus infection. Mechanistically, nuclear lncRNA-AVAN positively regulates the transcription of forkhead box O3A (FOXO3a) by associating with its promoter and inducing chromatin remodeling to promote neutrophil chemotaxis. Furthermore, we also found that cytoplasmic lncRNA-AVAN directly binds tripartite motif containing 25 (TRIM25) and enhances the association of TRIM25 and Retinoic acid inducible gene-1 proteins (RIG-I) and the ubiquitylation of RIG-I, thereby promoting TRIM25- and RIG-I-mediated antiviral innate immune signaling. More importantly, we enforced the expression of AVAN in transgenic mice and found that it significantly alleviated IAV virulence and virus production. Collectively, these findings highlight the potential clinical implications of lncRNA-AVAN as a key positive regulator of the antiviral innate immune response and a promising target for developing broad antiviral therapeutics.",2019-10-22,"Lai, C.; liu, l.; liu, q.; cheng, s.; wang, k.; zhao, l.; xia, m.; gu, h.; wang, c.; duan, y.; zhao, z.; zhang, l.; liu, z.; Luo, J.; Song, J.; Yang, P.; Chen, R.; Wang, X.",,,,True
d010cc0209bc5a0eee6259f72c42590c448da1cf,biorxiv,Gut microbiota structure differs between honey bees in winter and summer,doi.org/10.1101/703512,,,See https://www.biorxiv.org/about-biorxiv,"Adult honey bees harbor a specialized gut microbiota of relatively low complexity. While seasonal differences in community composition have been reported, previous studies have focused on compositional changes rather than differences in absolute bacterial loads. Moreover, little is known about the gut microbiota of winter bees, which live much longer than bees during the foraging season, and which are critical for colony survival. We quantified seven core members of the bee gut microbiota in a single colony over two years and characterized the community composition in 14 colonies during summer and winter. Our data shows that total bacterial loads substantially differ between foragers, nurses, and winter bees. Long-lived winter bees had the highest bacterial loads and the lowest community -diversity, with a characteristic shift towards high levels of Bartonella and Commensalibacter, and a reduction of opportunistic colonizers. Using gnotobiotic bee experiments, we show that diet is a major contributor to the observed differences in bacterial loads. Overall, our study reveals that the gut microbiota of winter bees is remarkably different from foragers and nurses. Considering the importance of winter bees for colony survival, future work should focus on the role of the gut microbiota in winter bee health and disease.",2019-10-23,"Kesnerova, L.; Emery, O.; Troilo, M.; Liberti, J.; Erkosar, B.; Engel, P.",,,,True
a7804d77d1a75810af0148d8fea8acbe2941f1b9,biorxiv,The effect of variant interference on de novo assembly for viral deep sequencing,doi.org/10.1101/815480,,,See https://www.biorxiv.org/about-biorxiv,"Viruses have high mutation rates and generally exist as a mixture of variants in biological samples. Next-generation sequencing (NGS) approach has surpassed Sanger for generating long viral sequences, yet how variants affect NGS de novo assembly remains largely unexplored. Our results from >15,000 simulated experiments showed that presence of variants can turn an assembly of one genome into tens to thousands of contigs. This \""variant interference\"" (VI) is highly consistent and reproducible by ten most used de novo assemblers, and occurs independent of genome length, read length, and GC content. The main driver of VI is pairwise identities between viral variants. These findings were further supported by in silico simulations, where selective removal of minor variant reads from clinical datasets allow the \""rescue\"" of full viral genomes from fragmented contigs. These results call for careful interpretation of contigs and contig numbers from de novo assembly in viral deep sequencing.",2019-10-23,"Castro, C. J.; Marine, R. L.; Ramos, E.; Ng, T. F. F.",,,,True
d2c7ac58cc309df9d3da8e766184d09c32d16dca,biorxiv,TaxIt: An iterative and automated computational pipeline for untargeted strain-level identification using MS/MS spectra from pathogenic samples,doi.org/10.1101/812313,,,See https://www.biorxiv.org/about-biorxiv,"Untargeted accurate strain-level classification of a priori unidentified organisms using tandem mass spectrometry is a challenging task. Reference databases often lack taxonomic depth, limiting peptide assignments to the species level. However, the extension with detailed strain information increases runtime and decreases statistical power. In addition, larger databases contain a higher number of similar proteomes.\n\nWe present TaxIt, an iterative workflow to address the increasing search space required for MS/MS-based strain-level classification of samples with unknown taxonomic origin. TaxIt first applies reference sequence data for initial identification of species candidates, followed by automated acquisition of relevant strain sequences for low level classification. Furthermore, proteome similarities resulting in ambiguous taxonomic assignments are addressed with an abundance weighting strategy to improve candidate confidence.\n\nWe apply our iterative workflow on several samples of bacterial and viral origin. In comparison to non-iterative approaches using unique peptides or advanced abundance correction, TaxIt identifies microbial strains correctly in all examples presented (with one tie), thereby demonstrating the potential for untargeted and deeper taxonomic classification. TaxIt makes extensive use of public, unrestricted and continuously growing sequence resources such as the NCBI databases and is available under open-source license at https://gitlab.com/rki_bioinformatics.",2019-10-24,"Kuhring, M.; Doellinger, J.; Nitsche, A.; Muth, T.; Renard, B. Y.",,,,True
c14d50924f959d38ff7857e6db3a60c929448956,biorxiv,Infectious bronchitis virus regulates cellular stress granule signaling,doi.org/10.1101/819482,,,See https://www.biorxiv.org/about-biorxiv,"Viruses must hijack cellular translation machinery to efficiently express viral genes. In many cases, this is impeded by cellular stress responses. These stress responses swiftly relocate and repurpose translation machinery, resulting in global inhibition of translation and the aggregation of stalled 48S mRNPs into cytoplasmic foci called stress granules. This results in translational silencing of all mRNAs excluding those beneficial for the cell to resolve the specific stress. For example, expression of antiviral factors is maintained during viral infection. Here we investigated stress granule regulation by Gammacoronavirus infectious bronchitis virus (IBV), which causes the economically important poultry disease, infectious bronchitis. Interestingly, we found that IBV is able to inhibit multiple cellular stress granule signaling pathways whilst at the same time IBV replication also results in induction of seemingly canonical stress granules in a proportion of infected cells. Moreover, IBV infection uncouples translational repression and stress granule formation and both processes are independent of eIF2 phosphorylation. These results provide novel insights into how IBV modulates cellular translation and antiviral stress signaling.",2019-10-28,"Brownsword, M. J.; Doyle, N.; Brocard, M.; Locker, N.; Maier, H. J.",,,,True
50aa3305f87a409bd1601bdec5d3cd404fe825a3,biorxiv,HUMAN BOCAVIRUS PREVALENCE IN CHILDREN WITH ACUTE GASTROENTERITIS FROM RURAL COMMUNITIES IN THE NORTHEN REGION OF SOUTH AFRICA,doi.org/10.1101/830281,,,See https://www.biorxiv.org/about-biorxiv,"BACKGROUNDAcute gastroenteritis (AGE) is a leading cause of morbidity and mortality in young children worldwide. Human Bocavirus (HBoV) is an emerging virus globally associated with diarrhea. The aim of this study was to demonstrate the prevalence of HBoV genotypes in children ([&le;]5 years) from rural communities in South Africa (SA) suffering from AGE.\n\nMATERIAL AND METHODA total of 141 fecal samples of children [&le;]5 years with acute gastroenteritis (AGE) were collected from rural Primary Health Care facilities in the Vhembe district of SA between June 2017 and July 2018. Clinical symptoms and demographic data were also recorded. A total of 102 (72%) were outpatients and 39 (28%) were hospitalized patients. Human Bocavirus (HBoV) genotypes were determined using Real-Time Multiplex PCR. DNA extracts of positive samples were confirmed by conventional PCR targeting the NS1 gene. Co-infection with other enteric viruses were determined in HBoV positive samples using Real-Time PCR.\n\nRESULTSHBoV was detected in 8 (5.7%) children with AGE. Children were in the age group between 1-24 months. HBoV1 and HBoV3 genotypes were each detected in 3 (37.5%) stool samples and HBoV2 in 2 (25%) stool samples. Co-infection with other enteric viruses included Rotavirus (37.5%); Adenovirus (37.5%); Norovirus (25%) and Astrovirus (12.5%).\n\nCONCLUSIONHBoV infections could be seen as a potential emerging diarrheal pathogen in South Africa. Further studies are required to understand the role of HBoV infections in children and adults with acute gastroenteritis.\n\nAuthor summaryAcute gastroenteritis (AGE) is recognized as a major cause for mortality in children [&le;]5 years of age in Africa and other developing countries. Viruses known to be involved in AGE includes Rotavirus, Norovirus, Astrovirus and Adenovirus and have been reported globally. Recently the Human Bocavirus (HBoV) have been reported in numerous studies globally as a potential cause of diarrhea. In this study, the prevalence and genetic diversity of human Bocavirus in children with AGE from rural communities in Limpopo, South Africa were investigated. In total, 141 stool samples from children [&le;] 5 years with AGE were assessed for the presence of HBoV using Real-Time PCR. HBoV were detected in 8 (5.7%) patients and included 3 positive samples for HBoV1 and HBoV3 respectively and 2 positive for HBoV2. No HBoV4 were detected. Among the 8 positive HBoV samples, co-infection with other enteric viruses were found in 7 (87.5%) samples, while mono infection with HBoV alone was detected in 1 (12.5%) patient. HBoV mixed infection with Rotavirus (3/8; 37.5%); Adenovirus (3/8; 37.5%); Norovirus (2/8; 25%) and Astrovirus (1/8; 12.5%) were observed in this study. This study reported for the first time on the prevalence of human Bocavirus in children with AGE from rural communities in South Africa.",2019-11-04,"Rikhotso, M.; Khumela, R.; Kabue, J. P.; Traore, A. N.; Potgieter, N.",,,,True
7c17c6f5e434f1d8227c9d8c5f9da26200364491,biorxiv,Probing the unfolded protein response to mouse hepatitis virus coronavirus infection through RNA sequencing and ribosome profiling,doi.org/10.1101/292979,,,See https://www.biorxiv.org/about-biorxiv,"Coronaviruses (CoVs) are enveloped, positive-sense RNA viruses with an unusually large RNA genome and a unique replication strategy. They cause important diseases in mammals and birds ranging from enteritis in cows and pigs and upper respiratory disease in chickens, to potentially lethal human respiratory infections. Here, we apply ribosome profiling and parallel RNA sequencing to analyse global changes in host cell transcriptome and translatome upon infection with mouse hepatitis virus strain A59 (MHV-A59), a model murine coronavirus in the same genus as the human pathogens severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Amongst differentially-regulated cellular genes, we observed up-regulation of all arms of the unfolded protein response (UPR), including translational activation of transcription factors ATF4, ATF5 and Chop. Polysome profiling of infected-cells revealed an accumulation of empty 80S ribosomes, consistent with increased phosphorylation of eIF2 leading to translational shut-off via inhibited initiation. Ribosomal footprints on phosphorylated-eIF2-resistant mRNAs revealed unambiguous upstream open reading frame (uORF) occupancy consistent with host maintenance of the UPR. Unexpectedly, an inhibitor of PERK that blocks the UPR and relieves translation inhibition was found to attenuate virus growth suggesting that MHV may subvert the UPR to its own advantage. This study sheds new light on the complex interactions between MHV and host during infection and provides new potential targets for antiviral intervention.",2019-11-13,"Cook, G. M.; Brown, K.; Franaszek, K.; Moore, N. A.; Siddell, S. G.; Brierley, I.; Firth, A. E.; Irigoyen, N.",,,,True
54122e9771f67d234bdcc67172a788bc96eec34e,biorxiv,Loss of IKK subunits limits NF-κB signaling in reovirus infected cells,doi.org/10.1101/843680,,,See https://www.biorxiv.org/about-biorxiv,"Viruses commonly antagonize innate immune pathways that are primarily driven by Nuclear Factor-{kappa}B (NF-{kappa}B), Interferon Regulatory Factor (IRF) and Signal Transducer and Activator of Transcription (STAT) family of transcription factors. Such a strategy allows viruses to evade immune surveillance and maximize their replication. Using an unbiased RNA-seq based approach to measure gene expression induced by transfected viral genomic RNA (vgRNA) and reovirus infection, we discovered that mammalian reovirus inhibits host cell innate immune signaling. We found that while vgRNA and reovirus infection both induce a similar IRF dependent gene expression program, gene expression driven by the NF-{kappa}B family of transcription factors is lower in infected cells. Potent agonists of NF-{kappa}B, such as Tumor Necrosis Factor alpha (TNF) and vgRNA, failed to induce NF-{kappa}B dependent gene expression in infected cells. We demonstrate that NF-{kappa}B signaling is blocked due to loss of critical members of the Inhibitor of KappaB Kinase (IKK) complex, NF-{kappa}B Essential MOdifier (NEMO) and IKK{beta}. The loss of the IKK complex components prevents nuclear translocation and phosphorylation of NF-{kappa}B, thereby preventing gene expression. Our studies demonstrate that reovirus infection selectively blocks NF-{kappa}B, likely to counteract its antiviral effects and promote efficient viral replication.  IMPORTANCEHost cells mount a response to curb virus replication in infected cells and prevent infection of neighboring, as yet uninfected cells. The NF-{kappa}B family of proteins is important for the cell to mediate this response. In this study, we show that in cells infected with mammalian reovirus, NF-{kappa}B is inactive. Further, we demonstrate that NF-{kappa}B is rendered inactive because virus infection results in reduced levels of upstream intermediaries (called IKKs) that are needed for NF-{kappa}B function. Based on previous evidence that active NF-{kappa}B limits reovirus infection, we conclude that inactivating NF-{kappa}B is a viral strategy to produce a cellular environment that is favorable for virus replication.",2019-11-15,"McNamara, A. J.; Danthi, P.",,,,True
30457ee3ce0001f33938fbc246b4ce4eacd74f5d,biorxiv,ZODIAC: database-independent molecular formula annotation using Gibbs sampling reveals unknown small molecules,doi.org/10.1101/842740,,,See https://www.biorxiv.org/about-biorxiv,"1The confident high-throughput identification of small molecules remains one of the most challenging tasks in mass spectrometry-based metabolomics. SIRIUS has become a powerful tool for the interpretation of tandem mass spectra, and shows outstanding performance for identifying the molecular formula of a query compound, being the first step of structure identification. Nevertheless, the identification of both molecular formulas for large compounds above 500 Daltons and novel molecular formulas remains highly challenging. Here, we present ZODIAC, a network-based algorithm for the de novo estimation of molecular formulas. ZODIAC reranks SIRIUS molecular formula candidates, combining fragmentation tree computation with Bayesian statistics using Gibbs sampling. Through careful algorithm engineering, ZODIACs Gibbs sampling is very swift in practice. ZODIAC decreases incorrect annotations 16.2-fold on a challenging plant extract dataset with most compounds above 700 Dalton; we then show improvements on four additional, diverse datasets. Our analysis led to the discovery of compounds with novel molecular formulas such as C24H47BrNO8P which, as of today, is not present in any publicly available molecular structure databases.",2019-11-16,"Ludwig, M.; Nothias, L.-F.; Dührkop, K.; Koester, I.; Fleischauer, M.; Hoffmann, M. A.; Petras, D.; Vargas, F.; Morsy, M.; Aluwihare, L.; Dorrestein, P.; Böcker, S.",,,,True
9e780780dbaf35c0d537ddb290dfd484148a3c55,biorxiv,Estimating the Relative Probability of Direct Transmission between Infectious Disease Patients,doi.org/10.1101/612945,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundEstimating infectious disease parameters such as the serial interval (time between symptom onset in primary and secondary cases) and reproductive number (average number of secondary cases produced by a primary case) are important to understand infectious disease dynamics. Many estimation methods require linking cases by direct transmission, a difficult task for most diseases.  MethodsUsing a subset of cases with detailed genetic or contact investigation data to develop a training set of probable transmission events, we build a model to estimate the relative transmission probability for all case-pairs from demographic, spatial and clinical data. Our method is based on naive Bayes, a machine learning classification algorithm which uses the observed frequencies in the training dataset to estimate the probability that a pair is linked given a set of covariates.  ResultsIn simulations we find that the probabilities estimated using genetic distance between cases to define training transmission events are able to distinguish between truly linked and unlinked pairs with high accuracy (area under the receiver operating curve value of 95%). Additionally only a subset of the cases, 10-50% depending on sample size, need to have detailed genetic data for our method to perform well. We show how these probabilities can be used to estimate the average effective reproductive number and apply our method to a tuberculosis outbreak in Hamburg, Germany.  ConclusionsOur method is a novel way to infer transmission dynamics in any dataset when only a subset of cases has rich contact investigation and/or genetic data.  KEY MESSAGESO_LIThis method provides a way to calculate the relative probability that two infectious disease patients are connected by direct transmission using clinical, demographic, geographic, and genetic characteristics. C_LIO_LIWe use a naive Bayes, a machine learning technique to estimate these probabilities using a training set of probable links defined by contact investigation or pathogen WGS data on a subset of cases. C_LIO_LIThese probabilities can be used to explore possible transmission chains, rule out transmission events, and estimate the reproductive number. C_LI",2019-11-19,"Leavitt, S. V. N.; Lee, R. S.; Sebastiani, P.; Horsburgh, C. R.; Jenkins, H. E.; White, L. F.",,,,True
e1632ff25e6c30d4d89828154be1389a90109db8,biorxiv,Comparative genomics reveals signature regions used to develop a robust and sensitive multiplex TaqMan real-time qPCR assay to detect the genus Dickeya and Dickeya dianthicola,doi.org/10.1101/847590,,,See https://www.biorxiv.org/about-biorxiv,"AimsDickeya species are high consequence plant pathogenic bacteria listed among the quarantine pathogens of the European Union; associated with potato disease outbreaks and subsequent economic losses worldwide. Early, accurate, and reliable detection of Dickeya spp. is needed to prevent establishment and further dissemination of this pathogen. Therefore, a multiplex TaqMan qPCR was developed for sensitive detection of Dickeya spp. and specifically, D. dianthicola.  Methods and ResultsA signature genomic region for the genus Dickeya (mglA/mglC) and unique genomic region for D. dianthicola (alcohol dehydrogenase) were identified using a whole genome based comparative genomics approach. The developed multiplex TaqMan qPCR was validated using extensive inclusivity and exclusivity panels, and naturally/artificially infected samples to confirm broad range detection capability and specificity. Both sensitivity and spiked assays showed detection limit of 10 fg DNA.  ConclusionThe developed multiplex assay is sensitive and reliable to detect Dickeya spp. and D. dianthicola with no false positives or false negatives. It was able to detect mixed infection from naturally and artificially infected plant materials.  Significance and ImpactThe developed assay will serve as a practical tool for screening of propagative material, monitoring the presence and distribution, and quantification of target pathogens in a breeding program. The assay also has applications in routine diagnostics, biosecurity and microbial forensics.",2019-11-20,"Dobhal, S.; Boluk, G.; Babler, B.; Stulberg, M. J.; Rascoe, J.; Nakhla, M.; Chapman, T. A.; Crockford, A. B.; Melzer, M.; Alvarez, A. M.; Arif, M.",,,,True
c2510fbc213aa74c6c3195cbc8033c7d0f11b248,biorxiv,Deoxynivalenol Promotes Porcine Epidemic Diarrhea Virus Infection and Aggravates Gut Barrier Injury,doi.org/10.1101/852608,,,See https://www.biorxiv.org/about-biorxiv,"Porcine epidemic diarrhea virus (PEDV) is a highly contagious pathogenic virus that causes severe diarrhea and dehydration in pigs of all ages. Deoxynivalenol (DON), the most abundant trichothecene in food and feed, causes vomit and diarrhea in animals and human. However, whether DON exposure could affect PEDV infection remains unknown. Herein, we investigated the impacts of DON on entry and replication of PEDV, morbidity situation of piglets and the mechanisms involved. In vivo, twenty-seven piglets infected naturally with PEDV were randomly divided into three groups, receiving the basal diet containing 0, 750 and 1500 g/kg DON, respectively. We observed significant increases in the diarrhea rates, the villous injury of jejunums and the PEDV proliferation of duodenum, jejunum, ileum and mesenterium of piglets in experimental groups compared with control. Additionally, the autophagosome-like vesicles and the autophagy-related protein expressions were also increased in experimental groups. In vitro, we observed that, approximately 2 hrs post-infection, 0.1, 0.5 and 1.0 M DON promoted PEDV entry (P < 0.05) in IPEC-J2s and resulted in tight junction protein occludin internalization. Knockdown of occludin and CRISPR-Cas9-mediated knockout of LC3B indicated a vital role of autophagy-induced occludin internalization in DON-promoted PEDV entry. We also observed that, 24 hrs post-infection, a significant increase in PEDV replication after 0.1, 0.5 and 1.0 M DON treatment, along with the induction of a complete autophagy. Specifically, deletion of LC3B indicated a crucial role of autophagy in DON-promoted PEDV replication. Pretreatment with SB202190, a p38 signaling inhibitor, abolished the induction of autophagy. Furthermore, downregulation of type I interferon revealed that DON contributed PEDV to escape innate immune. Mechanistically, DON-caused innate immune escape was related to the upregulation of LC3B, which further inhibited STING phosphorylation. Taken together, DON could promote PEDV infection by inducing occludin internalization and innate immune escape via triggering p38-mediated autophagy.  Author summaryPorcine epidemic diarrhea (PED), a devastating enteric disease, leads to catastrophic economic loss to the global pig industry. Its primary pathogen is the coronavirus PED virus (PEDV). Growing evidence indicates that pathogen infection is not the only factor of PED outbreaks, other non-infectious factors is also related to this disease. We guessed some ubiquitous substances, such as deoxynivalenol (DON), that lead to pig intestinal epithelial cell stress might encourage the progress and spread of PED. In the present study, the weaning piglets infected naturally with PEDV and the IPEC-J2 cell line were selected as models to explore the effects of DON on PEDV infection, morbidity and gut barrier. Our results showed that DON exposure can promote PEDV infection in vitro and in vivo, and the underlying mechanism might be related to LC3B-mediated autophagy. Our findings reveal new pathways for developing potential novel antiviral strategies against PEDV infection.",2019-11-22,"Huang, K.; Liu, D.; Ge, L.; Wang, Q.; Su, J.; Chen, X.; Wang, C.",,,,True
3d5093a8e079fb17262111e5ef94bf01a3007971,biorxiv,HIGH PREVALENCE OF STRONGYLOIDIASIS IN SPAIN: A HOSPITAL-BASED STUDY,doi.org/10.1101/852558,,,See https://www.biorxiv.org/about-biorxiv,"Strongyloidiasis is a prevailing helminth infection ubiquitous in tropical and subtropical areas. However, prevalence data are scarce in migrant populations.  This study aims at evaluating the prevalence of S. stercoralis at hospital level in migrant populations or long term travellers being attended in out-patient and in-patient units as part of a systematic screening implemented in 6 Spanish hospitals. A cross-sectional study was conducted and systematic screening for S. stercoralis infection using serological tests was offered to all eligible participants. The overall seroprevalence of S. stercoralis was 9.04% (95% confidence interval [95%CI] 7.76 -10.31). The seroprevalence of people with a risk of infection acquired in Africa and Latin America was 9.35% (95%CI 7.01-11.69), 9.22% (7.5-10.93), respectively. The number of individuals coming from Asian countries was significantly smaller and the overall prevalence in these countries was 2.9% (95%CI -0.3; -6.2). There was only one case (1/14 (7.14%) from an individual from East European countries. The seroprevalence in units attending potentially immunosuppressed patients was significantly lower (5.64%) compared with the seroprevalence in other units of the hospital (10.20%) or Tropical diseases units (13.33%) (p<0.001). Conclusions: We report a hospital-based systematic screening of strongyloidiasis with a seroprevalence of almost 10% in a mobile population coming from endemic areas suggesting the need of implementing strongyloidiasis screening in hospitalized patients coming from endemic areas, particularly if they are at risk of immunosuppression.  Author summaryStrongyloidiasis is an infection caused by the helminth Strongyloides stercoralis which is ubiquitous in tropical and subtropical areas. In the rest of the countries, it is also frequent in migrants coming from tropical and subtropical areas. The disease is more severe when an infected subject has an impaired immune system. Within this study we have evaluated the prevalence of this infection in people being attended in six Spanish hospitals. The prevalence was around 9%, being higher in Africa and Latin America compared with other regions. In addition, the prevalence in patients with an impaired immune system (immunosuppression) was lower compared with people non suffering immunosuppression. These results suggest that the prevalence of strongyloidiasis is quite high among migrants living in Spain and that a screening programme should be designed, particularly in immunosuppressed patients that are at more risk of suffering severe complications of the infection.",2019-11-22,"Requena-Mendez, A.; Salas-Coronas, J.; Salvador, F.; Gomez-Junyent, J.; Villar-Garcia, J.; Santin, M.; Munoz, C.; Gonzalez-Cordon, A.; Cabezas-Fernandez, M. T.; Sulleiro, E.; Arenas, M. d. M.; Somoza, D.; Vazquez-Villegas, J.; Trevino, B.; Rodriguez, E.; Valls, M. E.; Subira, C.; Munoz, J.; Guillermos Girones, Philip Wikman, Manuel Jesus Soriano-Perez, Ana Belen Lozano,  ",,,,True
8367c21d603a58c206ae740debdb10099f84f198,biorxiv,VADR: validation and annotation of virus sequence submissions to GenBank,doi.org/10.1101/852657,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundGenBank contains over 3 million viral sequences. The National Center for Biotechnology Information (NCBI) previously made available a tool for validating and annotating influenza virus sequences that is used to check submissions to GenBank. Before this project, there was no analogous tool in use for non-influenza viral sequence submissions.  ResultsWe developed a system called VADR (Viral Annotation DefineR) that validates and annotates viral sequences in GenBank submissions. The annotation system is based on analysis of the input nucleotide sequence using models built from curated RefSeqs. Hidden Markov models are used to classify sequences by determining the RefSeq they are most similar to, and feature annotation from the RefSeq is mapped based on a nucleotide alignment of the full sequence to a covariance model. Predicted proteins encoded by the sequence are validated with nucleotide-to-protein alignments using BLAST. The system identifies 43 types of ""alerts"" that (unlike the previous BLAST-based system) provide deterministic and rigorous feedback to researchers who submit sequences with unexpected characteristics. VADR has been integrated into GenBanks submission processing pipeline allowing for viral submissions passing all tests to be accepted and annotated automatically, without the need for any human (GenBank indexer) intervention. Unlike the previous submission-checking system, VADR is freely available (https://github.com/nawrockie/vadr) for local installation and use. VADR has been used for Norovirus submissions since May 2018 and for Dengue virus submissions since January 2019. Other viruses with high numbers of submissions will be added incrementally.  ConclusionVADR improves the speed with which non-flu virus submissions to GenBank can be checked and improves the content and quality of the GenBank annotations. The availability and portability of the software allows researchers to run the GenBank checks prior to submitting their viral sequences, and thereby gain confidence that their submissions will be accepted immediately without the need to correspond with GenBank staff. Reciprocally, the adoption of VADR frees GenBank staff to spend more time on services other than checking routine viral sequence submissions.",2019-11-22,"Schäffer, A. A.; Hatcher, E.; Yankie, L.; Shonkwiler, L.; Brister, J. R.; Karsch-Mizrachi, I.; Nawrocki, E. P.",,,,True
a9a978c056422f979395ce56c96738d33b104a3e,biorxiv,The host antiviral ribonuclease L protein supports Zika virus replication factory formation to enhance infectious virus production,doi.org/10.1101/852194,,,See https://www.biorxiv.org/about-biorxiv,"The flavivirus Zika virus (ZIKV) activates ribonuclease L (RNase L) catalytic antiviral function during infection, yet deletion of RNase L decreases ZIKV production, suggesting a proviral role of RNase L. In this study, we reveal that latent RNase L supports ZIKV replication factory (RF) assembly. Deletion of RNase L induced broader cellular distribution of ZIKV dsRNA and NS3 compared with densely concentrated RFs detected in WT cells. An inactive form of RNase L was sufficient to contain ZIKV genome and dsRNA within a smaller area, which increased levels of viral RNA within RFs as well as infectious ZIKV released from the cell. We used a microtubule stabilization drug to demonstrate that RNase L deletion impaired the cytoskeleton rearrangements that are required for proper generation of RFs. During infection with dengue or West Nile Kunjin viruses, RNase L decreased virus production, suggesting that RNase L proviral function is specific to ZIKV.",2019-11-24,"Whelan, J. N.; Hatterschide, J.; Renner, D. M.; Dong, B.; Silverman, R. H.; Weiss, S. R.",,,,True
d5f7332f6dba1d990d54b5887a175e530d144130,biorxiv,Optimising Renewal Models for Real-Time Epidemic Prediction and Estimation,doi.org/10.1101/835181,,,See https://www.biorxiv.org/about-biorxiv,"The effective reproduction number, Rt, is an important prognostic for infectious disease epidemics. Significant changes in Rt can forewarn about new transmissions or predict the efficacy of interventions. The renewal model infers Rt from incidence data and has been applied to Ebola virus disease and pandemic influenza outbreaks, among others. This model estimates Rt using a sliding window of length k. While this facilitates real-time detection of statistically significant Rt fluctuations, inference is highly k -sensitive. Models with too large or small k might ignore meaningful changes or over-interpret noise-induced ones. No principled k -selection scheme exists. We develop a practical yet rigorous scheme using the accumulated prediction error (APE) metric from information theory. We derive exact incidence prediction distributions and integrate these within an APE framework to identify the k best supported by available data. We find that this k optimises short-term prediction accuracy and expose how common, heuristic k -choices, which seem sensible, could be misleading.",2019-11-26,"Parag, K. V.; Donnelly, C. A.",,,,True
107f0d5a47f48f85d6645cac0e7008edc4d9d8cd,biorxiv,Quantitative delineation of herpesviruses in bats for use in ecological studies,doi.org/10.1101/856518,,,See https://www.biorxiv.org/about-biorxiv,"Public health concerns about recent viral epidemics have motivated researchers to seek transdisciplinary understanding of infection in wildlife hosts. With its deep history devoted to explaining the abundance and distribution of organisms, ecology can augment current methods for studying viral dynamics. However, datasets allowing ecological explorations of viral communities are lacking, and common methods for delineating viral operational taxonomic units (OTUs), or ""species"", are subjective. Here, we comprehensively sampled 1,086 bats from two Puerto Rican caves and tested them for infection with herpesviruses. Using percent identity of nucleotides and a machine learning algorithm, we categorized herpesviruses into 41 OTUs, representing approximately 80% of all herpesviruses in the host community. Although 13 OTUs were detected in multiple host species, OTUs generally exhibited host specificity by infecting a core host species at a significantly higher prevalence than in all other species combined. Only two OTUs showed significantly different prevalence between host sexes. This work is the first exploration of viral community ecology in a community of wildlife hosts.",2019-11-26,"Sjodin, A. R.; Willig, M. R.; Anthony, S. J.",,,,True
87bfa13221ccf5a02d4a888ef1320b57f2c2d5e2,biorxiv,Reprogrammed Pteropus Bat Stem Cells Present Distinct Immune Signature And Are Highly Permissive For Henipaviruses,doi.org/10.1101/846410,,,See https://www.biorxiv.org/about-biorxiv,"Bats are unique among mammals due to the ability of powered flight and exceptional longevity. They are also asymptomatic hosts for numerous viruses, including recently emerged zoonotic Henipaviruses Nipah and Hendra, which are highly pathogenic for humans and other mammals. Better understanding of how bats control viral infection requires development of relevant permissive cellular experimental models. By applying a somatic reprogramming protocol to Pteropus bat primary cells, using a novel combination of ESRRB, CDX2, and c-MYC transcription factors, we generated bat reprogrammed cells exhibiting stem cell-like characteristics and a neural stem cell-like molecular signature. These cells present a unique interferon-stimulated transcriptomic signature and both produce and respond to interferon type-I, highlighting differences between stem cells from bats and other mammals. In contrast to primary bat cells, these reprogrammed cells are highly susceptible to infection by Henipavirus, thereby enabling isolation of new bat viruses, study of virus-bat interactions, and better understanding of bat biology.  Summary sentenceSomatic reprogramming provides new bat stem cells with unique immune properties and original viral permissivness",2019-11-30,"Aurine, N.; Baquerre, C.; Gaudino, M.; Jean, C.; Dumont, C.; Gervier, S.; Kress, C.; Horvat, B.; Pain, B.",,,,True
96ef1767754a53f792951ba1752440ae94e90c60,biorxiv,Tuning antiviral CD8 T-cell response via proline-altered peptide ligand vaccination,doi.org/10.1101/862144,,,See https://www.biorxiv.org/about-biorxiv,"Viral escape from CD8+ cytotoxic T lymphocyte responses correlates with disease progression and represents a significant challenge for vaccination. Here, we demonstrate that CD8+ T cell recognition of the naturally occurring MHC-I-restricted LCMV-associated immune escape variant Y4F is restored following vaccination with a proline-altered peptide ligand (APL). The APL increases MHC/peptide (pMHC) complex stability, rigidifies the peptide and facilitates T cell receptor (TCR) recognition through reduced entropy costs. Structural analyses of pMHC complexes before and after TCR binding, combined with biophysical analyses, revealed that although the TCR binds similarly to all complexes, the p3P modification alters the conformations of a very limited amount of specific MHC and peptide residues, facilitating efficient TCR recognition. This approach can be easily introduced in peptides restricted to other MHC alleles, and can be combined with currently available and future vaccination protocols in order to prevent viral immune escape.  Author SummaryViral escape mutagenesis correlates often with disease progression and represents a major hurdle for vaccination-based therapies. Here, we have designed and developed a novel generation of altered epitopes that re-establish and enhance significantly CD8+ T cell recognition of a naturally occurring viral immune escape variant. Biophysical and structural analyses provide a clear understanding of the molecular mechanisms underlying this reestablished recognition. We believe that this approach can be implemented to currently available or novel vaccination approaches to efficiently restore T cell recognition of virus escape variants to control disease progression.",2019-12-02,"Achour, A.; Duru, A. D.; Sun, R.; Allerbring, E. B.; Chadderton, J.; Kadri, N.; Han, X.; Uchtenhagen, H.; Madhurantakam, C.; Pellegrino, S.; Sandalova, T.; Nygren, P.-A.; Turner, S. J.",,,,True
feb8807e8418fdd6c4b8816ea761c9a68767a407,biorxiv,Novel tetraplex qPCR assays for simultaneous detection and identification of Xylella fastidiosa subspecies in plant tissues,doi.org/10.1101/699371,,,See https://www.biorxiv.org/about-biorxiv,"Xylella fastidiosa is an insect-borne bacterium confined to the xylem vessels of plants. This plant pathogen has a broad host range estimated to 560 plant species. Five subspecies of the pathogen with different but overlapping host ranges have been described, but only three subspecies are widely accepted, namely subspecies fastidiosa, multiplex and pauca. Initially limited to the Americas, Xf has been detected in Europe since 2013. As management of X. fastidiosa outbreaks in Europe depends on the identification of the subspecies, accurate determination of the subspecies in infected plants as early as possible is of major interest. Thus, we developed various tetraplex and triplex qPCR assays for Xylella fastidiosa detection and subspecies identification in planta in a single reaction. We designed primers and probes using SkIf, a bioinformatics tool based on k-mers, to detect specific signatures of the species and subspecies from a dataset of 58 genome sequences representative of X. fastidiosa diversity. We tested the qPCR assays on 39 target and 30 non-target strains, as well as on 13 different plant species spiked with strains of the different subspecies of X. fastidiosa, and on samples from various environmental and inoculated host plants. Sensitivity of simplex assays was equal or slightly better than the reference protocol on purified DNA. Tetraplex qPCR assays had the same sensitivity than the reference protocol and allowed X. fastidiosa detection in all spiked matrices up to 103 cells.mL-1. Moreover, mix infections of two to three subspecies could be detected in the same sample with tetraplex assays. In environmental plant samples, the tetraplex qPCR assays allowed subspecies identification when the current method based on multilocus sequence typing failed. The qPCR assays described here are robust and modular tools that are efficient for differentiating X. fastidiosa subspecies directly in plant samples.",2019-12-03,"Dupas, E.; Briand, M.; Jacques, M.-A.; Cesbron, S.",,,,True
815f653470c57a95b92e3857d8f5d038b4000d99,biorxiv,Processing of the SARS-CoV pp1a/ab nsp7-10 region,doi.org/10.1101/860049,,,See https://www.biorxiv.org/about-biorxiv,"1.1.Severe acute respiratory syndrome coronavirus (SARS-CoV) is the causative agent of a respiratory disease with a high case fatality rate. During the formation of the coronaviral replication/transcription complex (RTC), essential steps include processing of the conserved polyprotein nsp7-10 region by the main protease Mpro and subsequent complex formation of the released nsps. Here, we analyzed processing of the coronavirus nsp7-10 region using native mass spectrometry showing consumption of substrate, rise and fall of intermediate products and complexation. Importantly, there is a clear order of cleavage efficiencies, which is influenced by the polyprotein tertiary structure. Furthermore, the predominant product is an nsp7+8(2:2) hetero-tetramer with nsp8 scaffold. In conclusion, native MS, opposed to other methods, can expose the processing dynamics of viral polyproteins and the landscape of protein interactions in one set of experiments. Thereby, new insights into protein interactions, essential for generation of viral progeny, were provided, with relevance for development of antivirals.",2019-12-04,"Krichel, B.; Falke, S.; Hilgenfeld, R.; Redecke, L.; Uetrecht, C.",,,,True
a4d1861ceb0adf8dbdb8aed9465a3487fded5568,biorxiv,The demyelinating agent cuprizone induces a male-specific reduction in binge eating in the binge-prone C57BL/6NJ strain,doi.org/10.1101/865600,,,See https://www.biorxiv.org/about-biorxiv,"Binge eating (BE) is a heritable symptom of eating disorders with an unknown genetic etiology. Rodent models for BE of palatable food permit the study of genetic and biological mechanisms. We previously used genetic mapping and transcriptome analysis to map a coding mutation in Cyfip2 associated with increased BE in the BE-prone C57BL/6NJ substrain compared to the BE-resistant C57BL/6J substrain. The increase in BE in C57BL/6NJ mice was associated with a decrease in transcription of genes enriched for myelination in the striatum. Here, we tested the hypothesis that decreasing myelin levels with the demyelinating agent cuprizone would enhance BE. Mice were treated with a 0.3% cuprizone home cage diet for two weeks. Following a three-week recovery period, mice were trained for BE in an intermittent, limited access procedure. Cuprizone induced similar weight loss in both substrains and sexes that recovered within 48 h after removal of the cuprizone diet. Surprisingly, cuprizone reduced BE in male but not female C57BL/6NJ mice while having no effect in C57BL/6J mice. Cuprizone also reduced myelin basic protein (MBP) at seven weeks post-cuprizone removal while having no effect on myelin-associated glycoprotein (MAG) at this time point. C57BL/6N mice also showed less MBP than C57BL/6J mice. There were no statistical interactions of Treatment with Sex on MBP levels, indicating that differences in MBP are unlikely to account for sex differences in BE. To summarize, cuprizone induced an unexpected, male-specific reduction in BE which could indicate sex-specific biological mechanisms that depend on genetic background.",2019-12-05,"Babbs, R. K.; Beierle, J. A.; Kelliher, J. C.; Medeiros, A. R.; Anandakumar, J.; Shah, A.; Yao, E. J.; Chen, M. M.; Bryant, C. D.",,,,True
0255ea4b2f26a51a3bfa3bd8f3e1978c82c976d5,biorxiv,Carbon Nanocarriers Deliver siRNA to Intact Plant Cells for Efficient Gene Knockdown,doi.org/10.1101/564427,,,See https://www.biorxiv.org/about-biorxiv,"Post-transcriptional gene silencing (PTGS) is a powerful tool to understand and control plant metabolic pathways, which is central to plant biotechnology. PTGS is commonly accomplished through delivery of small interfering RNA (siRNA) into cells. While siRNA delivery has been optimized for mammalian systems, it remains a significant challenge for plants due to the plant cell wall. Standard plant siRNA delivery methods (Agrobacterium and viruses) involve coding siRNA into DNA vectors, and are only tractable for certain plant species. Herein, we develop a nanotube-based platform for direct delivery of siRNA, and show high silencing efficiency in intact plant cells. We demonstrate that nanotubes successfully deliver siRNA and silence endogenous genes owing to effective intracellular delivery and nanotube-induced protection of siRNA from nuclease degradation. This study establishes that nanotubes, which are below the size exclusion limit of the plant cell wall, could enable a myriad of plant biotechnology applications that rely on RNA delivery.",2019-12-12,"Demirer, G. S.; Zhang, H.; Goh, N. S.; Pinals, R. L.; Chang, R.; Landry, M. P.",,,,True
89dc136a94e00b3c51f00008928032c67d17a2e7,biorxiv,Delving below the species level to characterize the ecological diversity within the global virome: An exploration of West Nile Virus,doi.org/10.1101/2019.12.12.874214,,,See https://www.biorxiv.org/about-biorxiv,"Efforts to describe the diversity of viruses have largely focused on classifying viruses at the species level. However, substantial ecological diversity, both in virulence level and host range, is known within virus species. Here we demonstrate a proof of concept for easily discovering ecological diversity within a virus species taxon. We have focused on the West Nile Virus to take advantage of its broad host range in nature. We produced a genome-based phylogeny of world diversity of WNV and then used Ecotype Simulation 2 to hypothesize demarcation of genomes into 69 putative ecotypes (ecologically distinct populations), based only on clustering of genome sequences. Then we looked for evidence of ecological divergence among ecotypes based on differences in host bird associations within the Connecticut-New York region. Our results indicated significant heterogeneity among ecotypes for their associations with different bird hosts. Ecological diversity within other zoonotic viruses could be easily discovered using this approach. Opportunities for extending this line of research to human associations of virus ecotypes are limited by missing geographic metadata on human samples.",2019-12-13,"Kong, T.; Mei, K.; Wang, A.; Krizanc, D.; Cohan, F. M.",,,,False
97027e08cb413795cf19064338efd049fe5d491b,biorxiv,Novel splicing and open reading frames revealed by long-read direct RNA sequencing of adenovirus transcripts,doi.org/10.1101/2019.12.13.876037,,,See https://www.biorxiv.org/about-biorxiv,"Adenovirus is a common human pathogen that relies on host cell processes for production and processing of viral RNA. Although adenoviral promoters, splice junctions, and cleavage and polyadenylation sites have been characterized using low-throughput biochemical techniques or short read cDNA-based sequencing, these technologies do not fully capture the complexity of the adenoviral transcriptome. By combining Illumina short-read and nanopore long-read direct RNA sequencing approaches, we mapped transcription start sites and cleavage and polyadenylation sites across the adenovirus genome. The canonical viral early and late RNA cassettes were confirmed, but analysis of splice junctions within long RNA reads revealed an additional 20 novel viral transcripts. These RNAs include seven new splice junctions which lead to expression of canonical open reading frames (ORF), as well as 13 transcripts encoding for messages that potentially alter protein functions through truncations or the fusion of canonical ORFs. In addition, we also detect RNAs that bypass canonical cleavage sites and generate potential chimeric proteins by linking separate gene transcription units. Our work highlights how long-read sequencing technologies can reveal further complexity within viral transcriptomes.",2019-12-13,"Price, A. M.; Hayer, K. E.; Depledge, D. P.; Wilson, A. C.; Weitzman, M. D.",,,,True
75216c0238ddc17dec8ef66adcc84bd48922cae4,biorxiv,"Structurally informed evolutionary models improve phylogenetic reconstruction for emerging, seasonal, and pandemic influenza viruses",doi.org/10.1101/228692,,,See https://www.biorxiv.org/about-biorxiv,"Precise estimation of genetic substitution patterns is critical for accurate reconstruction of pathogen phylogenies. Few studies of viral evolution account for variations of mutation rate across a single gene. This is especially true when considering evolution of segmented viruses where individual segments are short, encoding for few proteins. However, the structural and functional partitions of these proteins could provide valuable information for more accurate inference of viral evolution, due to the disparate immune selection pressure on different functional domains. Accurately reconstructed evolutionary features on specific functional domains can in turn provide biological information on viral protein and immune targets for vaccine design. In this study we developed and evaluated a structurally informed partitioning scheme that accounts for rate variation among immunogenic head and stalk domains of the surface protein hemagglutinin (HA) of influenza viruses. We evaluated the model fit and performance of four different models - HKY, SRD06 codon, HKY with a structurally informed partitioning scheme, SRD06 with a structurally informed partitioning scheme on pandemic A/H1N1pdm09, seasonal A/H1N1postpdm, A/H3N2, B-Yamagata-like and Victoria-like lineages, and two highly pathogenic avian influenza A viruses H5Nx and H7N9. Results showed that structurally informed partitioning with SRD06 performed better for all datasets with decisively statistical support. Significantly faster nucleotide substitution rates for head domain, compared to stalk domain was observed and may provide insight for stalk derived broadly-reactive vaccine design. Taken together, integrating a functionally informed partitioning scheme based on protein structures of immune targets allows for significant improvement of phylogenetic analysis and providing important biological insights.",2019-12-13,"Qiu, X.; Bahl, J.",,,,True
93f67ffe7803061de9b19c4dfa346b3aa97aa4eb,biorxiv,Non-uniform refinement: Adaptive regularization improves single particle cryo-EM reconstruction,doi.org/10.1101/2019.12.15.877092,,,See https://www.biorxiv.org/about-biorxiv,"Single particle cryo-EM is a powerful method for studying proteins and other biological macromolecules. Many of these molecules comprise regions with varying structural properties including disorder, flexibility, and partial occupancy. These traits make computational 3D reconstruction from 2D images challenging. Detergent micelles and lipid nanodiscs, used to keep membrane proteins in solution, are common examples of locally disordered structures that can negatively affect existing iterative refinement algorithms which assume rigidity (or spatial uniformity). We introduce a cross-validation approach to derive non-uniform refinement, an algorithm that automatically regularizes 3D density maps during iterative refinement to account for spatial variability, yielding dramatically improved resolution and 3D map quality. We find that in common iterative refinement methods, regularization using spatially uniform filtering operations can simultaneously over- and under-regularize local regions of a 3D map. In contrast, non-uniform refinement removes noise in disordered regions while retaining signal useful for aligning particle images. Our results include state-of-the-art resolution 3D reconstructions of multiple membrane proteins with molecular weight as low as 90kDa. These results demonstrate that higher resolutions and improved 3D density map quality can be achieved even for small membrane proteins, an important use case for single particle cryo-EM, both in structural biology and drug discovery. Non-uniform refinement is implemented in the cryoSPARC software package and has already been used successfully in several notable structural studies.",2019-12-16,"Punjani, A.; Zhang, H.; Fleet, D. J.",,,,True
8bf46a4758744d1c12834b7e2dcfbbaef039e236,biorxiv,"Randomly primed, strand-switching MinION-based sequencing for the detection and characterization of cultured RNA viruses",doi.org/10.1101/2019.12.16.875872,,,See https://www.biorxiv.org/about-biorxiv,"RNA viruses rapidly mutate, which can result in increased virulence, increased escape from vaccine protection, and false negative detection results. Targeted detection methods have a limited ability to detect unknown viruses and often provide insufficient data to detect coinfections or identify antigenic variants. Random, deep sequencing is a method that can more fully detect and characterize RNA viruses and is often coupled with molecular techniques or culture methods for viral enrichment. Viral culture coupled with third-generation sequencing were tested for the ability to detect and characterize RNA viruses. Cultures of bovine viral diarrhea virus, canine distemper virus, epizootic hemorrhagic disease virus, infectious bronchitis virus, two influenza A viruses, and porcine respiratory and reproductive syndrome virus were sequenced on the MinION platform using a random, reverse primer in a strand-switching reaction, coupled with PCR-based barcoding. Reads were taxonomically classified and used for reference-based sequence building using a stock personal computer. This method accurately detected and identified complete coding sequence genomes with a minimum of 20x coverage depth for all seven viruses, including a sample containing two viruses. Each lineage-typing region had at least 26x coverage depth for all viruses. Furthermore, analyzing the canine distemper virus sample through a pipeline devoid of canine distemper virus reference sequences modeled the ability of this protocol to detect unknown viruses. These results show the ability of this technique to detect and characterize dsRNA, negative- and positive-sense ssRNA, nonsegmented, and segmented RNA viruses.",2019-12-17,"Young, K. T.; Lahmers, K. K.; Sellers, H. S.; Stallknecht, D. E.; Poulson, R. L.; Saliki, J. T.; Tompkins, S. M.; Padykula, I.; Siepker, C.; Howerth, E. W.; Todd, M.; Stanton, J. B.",,,,False
a555fbeeffc44dfdb5087c83395f0f743654cbba,biorxiv,A novel totivirus alters gene expression and vacuolar morphology in Malassezia cells and induces a TLR3-mediated inflammatory immune response,doi.org/10.1101/2019.12.17.880526,,,See https://www.biorxiv.org/about-biorxiv,"Most fungal viruses have been identified in plant pathogens, whereas the presence of viral particles in human pathogenic fungi is less well studied. In the present study, we observed extrachromosomal double-stranded RNA (dsRNA) segments in various clinical isolates of Malassezia species. Malassezia is the most dominant fungal genus on the human skin surface, and species in this group are considered to be etiological factors in various skin diseases including dandruff, seborrheic dermatitis, and atopic dermatitis. We identified novel dsRNA segments and our sequencing results revealed that the virus, named MrV40, belongs to the Totiviridae family and contains an additional satellite dsRNA segment encoding a novel protein. The transcriptome of virus-infected M. restricta cells was compared to that of virus-free cells, and the results showed that transcripts involved in ribosomal biosynthesis were down regulated and those involved in energy production and programmed cell death were increased in abundance. Moreover, transmission electron microscopy revealed significantly larger vacuoles for virus-infected M. restricta cells, indicating that MrV40 infection dramatically altered M. restricta physiology. Our analysis also revealed that a viral nucleic acid from MrV40 induces a TLR3-mediated inflammatory immune response in bone marrow-derived dendritic cells (BMDCs) and this result suggests that a viral element contributes to the pathogenesis of Malassezia.  ImportanceMalassezia is the most dominant fungal genus on the human skin surface and is associated with various skin diseases including dandruff and seborrheic dermatitis. Among Malassezia species, M. restricta is the most widely observed species on the human skin. In the current study, we identified a novel dsRNA virus, named MrV40, in M. restricta and characterized the sequences and structure of the viral genome along with an independent satellite dsRNA viral segment. Moreover, we found altered expression of genes involved in ribosomal synthesis and programmed cell death, indicating that virus infection altered the physiology of the fungal host cells. Our data also showed that the viral nucleic acid from MrV40 induces a TLR3-mediated inflammatory immune response in bone marrow-derived dendritic cells (BMDCs), indicating that a viral element likely contributes to the pathogenesis of Malassezia. This is the first study to identify and characterize a novel mycovirus in Malassezia.",2019-12-19,"Park, M.; Cho, Y.-J.; Kim, D.; Yang, C.-S.; Lee, S. M.; Dawson, T.; Nakamizo, S.; Kabashima, K.; Lee, Y. W.; Jung, W. H.",,,,True
73d80c8f5780d70bd8d343188c56e898e91557b6,biorxiv,Ca2+ ions promote fusion of Middle East Respiratory Syndrome coronavirus with host cells and increase infectivity,doi.org/10.1101/2019.12.18.881391,,,See https://www.biorxiv.org/about-biorxiv,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a major emerging zoonotic infectious disease. Since its first outbreak in 2012, the virus has repeatedly transmitted from camels to humans with 2,468 confirmed cases, causing 851 deaths. To date, there are no efficacious drugs and vaccines against MERS-CoV, increasing its potential to cause a public health emergency. A critical step in the life cycle of MERS-CoV is the fusion with the host cell with its spike (S) protein as main determinant of viral entry. Proteolytic cleavage of S exposes its fusion peptide (FP), which initiates membrane fusion. Previous studies on the related severe acute respiratory syndrome coronavirus (SARS-CoV) FP have shown that calcium (Ca2+) plays an important role for fusogenic activity via a Ca2+ binding pocket with conserved glutamic acid (E) and aspartic acid (D) residues. SARS-CoV and MERS-CoV FP share a high sequence homology and here, we investigated whether Ca2+ is required for MERS-CoV fusion by substituting E and D residues in the MERS-CoV FP with neutrally charged alanines. Upon verifying mutant cell surface expression and proteolytic cleavage, we tested the mutants ability to mediate infection of pseudo-particles (PPs) on host cells without and with Ca2+. Our results demonstrate that intracellular Ca2+ enhances MERS-CoV WT PPs infection by approximately two-fold and that E891 is a crucial residue for Ca2+ interaction. Electron spin resonance revealed that this enhancement could be attributed to Ca2+ increasing MERS-CoV FP fusion-relevant membrane ordering. Intriguingly, isothermal calorimetry titration showed that MERS-CoV FP binds one Ca2+, as opposed to SARS-CoV FP which binds two. Our data suggests that there are significant differences in FP-Ca2+ interactions of MERS-CoV and SARS-CoV FP despite their high sequence similarity and that the number of Ca2+ ions interacting with the FP has implications on the fusion dynamics of the virus.",2019-12-19,"Straus, M. R.; Tang, T.; Lai, A. L.; Flegel, A.; Bidon, M.; Freed, J. H.; Daniel, S.; Whittaker, G. R.",,,,True
63781701d3aac3b1640caae24b2c8c2a06c8e6ab,biorxiv,Comparison of alternative models of human movement and the spread of disease,doi.org/10.1101/2019.12.19.882175,,,See https://www.biorxiv.org/about-biorxiv,"Predictive models for the spatial spread of infectious diseases has received much attention in recent years as tools for the management of infectious diseas outbreaks. Prominently, various versions of the so-called gravity model, borrowed from transportation theory, have been used. However, the original literature suggests that the model has some potential misspecifications inasmuch as it fails to capture higher-order interactions among population centers. The fields of economics, geography and network sciences holds alternative formulations for the spatial coupling within and among conurbations. These includes Stouffers rank model, Fotheringhams competing destinations model and the radiation model of Simini et al. Since the spread of infectious disease reflects mobility through the filter of age-specific susceptibility and infectivity and since, moreover, disease may alter spatial behavior, it is essential to confront with epidemiological data on spread. To study their relative merit we, accordingly, fit variants of these models to the uniquely detailed dataset of prevaccination measles in the 954 cities and towns of England and Wales over the years 1944-65 and compare them using a consistent likelihood framework. We find that while the gravity model is a reasonable first approximation, both Stouffers rank model, an extended version of the radiation model and the Fotheringham competing destinations model provide significantly better fits, Stouffers model being the best. Through a new method of spatially disaggregated likelihoods we identify areas of relatively poorer fit, and show that it is indeed in densely-populated conurbations that higher order spatial interactions are most important. Our main conclusion is that it is premature to narrow in on a single class of models for predicting spatial spread of infectious disease. The supplemental materials contain all code for reproducing the results and applying the methods to other data sets.  Author summaryThe ability to predict how infectious disease will spread is of great importance in the face of the numerous emergent and re-emergent pathogens that currently threatening human well-being. We identified a variety of alternative models that predict human mobility as as a function of population distribution across a landscape. These consider some models that account for pair-wise interactions between population centers, as well as some that allow for higher-order interactions. We trained the models using a uniquely rich spatiotemporal data set on pre-vaccination measles in England and wales (1944-65), which comprises more than a million records from 954 cities and towns. Likelihood rankings of the different models reveal strong evidence for higher-order interactions in the form of competition among cities as destinations for travelers and, thus, dilution of spatial transmission. The currently most commonly used so-called  gravity models were far from the best in capturing spatial disease dynamics.",2019-12-19,"Bjornstad, O. N.; Grenfell, B.; Viboud, C.; King, A.",,,,True
8c223fd63ba6a924ecd3df8d32bcf0556758cb95,biorxiv,"Nanopore-based native RNA sequencing provides insights into prokaryotic transcription, operon structures, rRNA maturation and modifications",doi.org/10.1101/2019.12.18.880849,,,See https://www.biorxiv.org/about-biorxiv,"The prokaryotic transcriptome is shaped by transcriptional and posttranscriptional events that define the characteristics of an RNA, including transcript boundaries, the base modification status, and processing pathways to yield mature RNAs. Currently, a combination of several specialised short-read sequencing approaches and additional biochemical experiments are required to describe all transcriptomic features. In this study, we present native RNA sequencing of bacterial (E. coli) and archaeal (H. volcanii, P. furiosus) transcriptomes employing the Oxford Nanopore sequencing technology. Based on this approach, we could address multiple transcriptomic characteristics simultaneously with single-molecule resolution. Taking advantage of long RNA reads provided by the Nanopore platform, we could accurately (re-)annotate large transcriptional units and boundaries. Our analysis of transcription termination sites revealed that diverse termination mechanisms are in place in archaea. Moreover, we shed light on the poorly understood rRNA processing pathway in archaea and detected new processing intermediates. One of the key features of native RNA sequencing is that RNA modifications are retained. We could confirm this ability by analysing the well-known KsgA-dependent rRNA methylation sites. Notably, our analysis suggests that rRNA modifications are more abundant in a hyperthermophilic organism.",2019-12-19,"Grünberger, F.; Knüppel, R.; Jüttner, M.; Fenk, M.; Borst, A.; Reichelt, R.; Soppa, J.; Ferreira-Cerca, S.; Grohmann, D.",,,,True
d83e3c028de1950c4f8dedae21eb90f90c4ed6c3,biorxiv,Translational profiling of macrophages infected with Leishmania donovani identifies mTOR- and eIF4A-sensitive immune-related transcripts,doi.org/10.1101/2019.12.20.884338,,,See https://www.biorxiv.org/about-biorxiv,"The protozoan parasite Leishmania donovani (L. donovani) causes visceral leishmaniasis, a chronic infection which is fatal when untreated. While previous studies showed that L. donovani reprograms transcription to subvert host cell functions, it remains unclear whether the parasite also alters host mRNA translation to establish a successful infection. To assess this, we compared transcriptome-wide translation in primary mouse macrophages infected with L. donovani promastigotes or amastigotes using polysome-profiling. This identified ample selective changes in translation (3,127 transcripts) which were predicted to target central cellular functions by inducing synthesis of proteins related to chromatin remodeling and RNA metabolism while inhibiting those related to intracellular trafficking and antigen presentation. Parallel quantification of protein and mRNA levels for a set of transcripts whose translation was activated upon L. donovani infection (Papbpc1, Eif2ak2, and Tgfb) confirmed, as indicated by polysome-profiling, increased protein levels despite largely unaltered mRNA levels. Mechanistic in silico analyses suggested activated translation depending on the kinase mTOR (e.g. Pabpc1) and the RNA helicase eIF4A (e.g. Tgfb) during infection. Accordingly, treatment with mTOR inhibitors torin-1 or rapamycin reversed L. donovani-induced PABPC1 without affecting corresponding transcript levels. Similarly, the production of TGF-{beta} decreased in presence of the eIF4A inhibitor silvestrol despite unaltered Tgfb mRNA levels. Consistent with parasite modulation of host eIF4A-sensitive translation to promote infection, silvestrol suppressed L. donovani replication within macrophages. In contrast, parasite survival was favored under mTOR inhibition. In summary, infection-associated changes in translation of mTOR- and eIF4A-sensitive mRNAs contribute to modulate mRNA metabolism and immune responses in L. donovani-infected macrophages. Although the net outcome of such translation programs favours parasite propagation, individual translation programs appear to have opposing roles during L. donovani infection, thereby suggesting their selective targeting as key for therapeutic effects.  Author SummaryFine-tuning the efficiency of mRNA translation into proteins allows cells to tailor their responses to stress without the need for synthesizing new mRNA molecules. It is well established that the protozoan parasite Leishmania donovani alters transcription of specific genes to subvert host cell functions. However, discrepancies between transcriptomic and proteomic data suggest that post-transcriptional regulatory mechanisms also contribute to modulate host gene expression programs during L. donovani infection. Herein, we report that one third of protein-coding mRNAs expressed in macrophages are differentially translated upon infection with L. donovani. Our computational analyses reveal that subsets of mRNAs encoding functionally related proteins share the same directionality of translational regulation, which is likely to impact metabolic and microbicidal activity of infected cells. We also show that upregulated translation of transcripts that encode central regulators of mRNA metabolism and inflammation is sensitive to the activation of mTOR or eIF4A during infection. Finally, we observe that inhibition of eIF4A activity reduces parasite survival within macrophages while selective blockade of mTOR has the opposite effect. Thus, our study points to a dual role for translational control of host gene expression during L. donovani infection and suggests that novel regulatory nodes could be targeted for therapeutic intervention.",2019-12-20,"Chaparro, V.; Leroux, L.-P.; Masvidal, L.; Lorent, J.; Graber, T. E.; Zimmermann, A.; Arango Duque, G.; Descoteaux, A.; Alain, T.; Larsson, O.; Jaramillo, M.",,,,True
cb346b64e20934bc01f7727cf51494b22f172de0,biorxiv,Anesthetic agents affect urodynamic parameters and anesthetic depth at doses necessary to facilitate preclinical testing in felines,doi.org/10.1101/868398,,,See https://www.biorxiv.org/about-biorxiv,"Urodynamic studies, used to understand bladder function, diagnose bladder disease, and develop treatments for dysfunctions, are ideally performed with awake subjects. However, in animal models, especially cats (a common model of spinal cord injury and associated bladder pathology), anesthesia is often required for these procedures and can be a research confounder. This study compared the effects of select agents (dexmedetomidine, alfaxalone, propofol, isoflurane, and -chloralose) on urodynamic ({Delta}pressure, bladder capacity, bladder compliance, non-voiding contractions, bladder pressure slopes) and anesthetic (change in heart rate [{Delta}HR], average heart rate [HR], reflexes, induction/recovery times) parameters in repeated cystometrograms across five adult male cats. {Delta}pressure was greatest with propofol, bladder capacity was highest with -chloralose, non-voiding contractions were greatest with -chloralose. Propofol and dexmedetomidine had the highest bladder pressure slopes during the initial and final portions of the cystometrograms respectively. Cats progressed to a deeper plane of anesthesia (lower HR, smaller {Delta}HR, decreased reflexes) under dexmedetomidine, compared to propofol and alfaxalone. Time to induction was shortest with propofol, and time to recovery was shortest with dexmedetomidine. These agent-specific differences in urodynamic and anesthetic parameters in cats will facilitate appropriate study-specific anesthetic choices.",2019-12-23,"Xu, J. J.; Yousuf, Z.; Ouyang, Z.; Kennedy, E.; Lester, P.; Martin, T.; Bruns, T.",,,,True
4e7cd4e923777d6caaa76bb2b93f6121bcd5b6a3,biorxiv,First isolation and characterisation of Alongshan virus in Russia,doi.org/10.1101/862573,,,See https://www.biorxiv.org/about-biorxiv,"In recent decades, many new flavi-like viruses have been discovered predominantly in different invertebrates and, as was recently shown, some of them may cause disease in humans. The Jingmen tick virus (JMTV) group holds a special place among flavi-like viruses because, in contrast to the ""classic"" flaviviruses and other flavi-like viruses, they have a segmented ssRNA(+) genome. Two segments of the JMTV genome have homology with regions of the flavivirus genome encoding polymerase and helicase-protease proteins. JMTVs have several open reading frames (ORF) in segments encoding glycoprotein(s) and capsid protein and these ORF are specific only to them. JMTVs greatly differ in virion size.  We isolated three strains of Alongshan virus (ALSV), which is a representative of the JMTV group, from adult Ixodes persulcatus ticks collected in two geographically-separated Russian regions in the tick cell line IRE/CTVM19. One of the strains persisted in the IRE/CTVM19 cells without cytopathic effect for three years. Most virions purified from tick cells were spherical with a diameter of approximately 40.5 nm. In addition, we found smaller particles of approximately 13.1 nm in diameter. We obtained full genome sequences of all four segments of two of the isolated ALSV strains, and partial sequences of one segment from the third strain. Phylogenetic analysis on genome segment 2 of the JMTV group clustered our novel strains with other ALSV strains. We found evidence for the existence of a novel upstream ORF in the glycoprotein-coding segment of ALSV and other members of the JMTV group.  Significance StatementWe isolated three strains of Alongshan virus (ALSV) from adult Ixodes persulcatus ticks from two geographically separate areas of Russia in the Ixodes ricinus tick cell line IRE/CTVM19. One of the strains persisted in the IRE/CTVM19 cells without cytopathic effect for three years. Our study confirmed the value of tick cell lines in virus isolation and maintenance of persistent infection. The majority of virions of the ALSV strain Miass527 were enveloped spherical particles with a diameter of 40.5{+/-}3.7 nm. We found evidence for the existence of a novel upstream ORF in the glycoprotein-coding segment of ALSV and other members of the Jingmen tick virus group.",2019-12-23,"Kholodilov, I. S.; Litov, A. G.; Klimentov, A. S.; Belova, O. A.; Polienko, A. E.; Nikitin, N. A.; Shchetinin, A. M.; Ivannikova, A. Y.; Bell-Sakyi, L.; Yakovlev, A. S.; Bugmyrin, S. V.; Bespyatova, L. A.; Gmyl, L. V.; Luchinina, S. V.; Gmyl, A. P.; Gushchin, V. A.; Karganova, G. G.",,,,True
d2616cd5feadf2f63508144580ce2b9e172decf5,biorxiv,Interleukin-33 promotes type 1 cytokine expression via p38 MAPK in human natural killer cells,doi.org/10.1101/777847,,,See https://www.biorxiv.org/about-biorxiv,"This study tests the hypothesis that activation of mitogen-activated protein kinase (MAPK) by physiologically-relevant concentrations of interleukin-33 (IL-33) contributes to enhanced cytokine expression by IL-12 stimulated human natural killer (NK) cells. While IL-33 canonically triggers type 2 cytokine responses, this cytokine can also synergize with type 1 cytokines like IL-12 to provoke interferon-gamma (IFN-{gamma}). We show that picogram concentrations of IL-12 and IL-33 are sufficient to promote robust secretion of IFN-{gamma} by human NK cells that greatly exceeds responses to either cytokine alone. Nanogram doses of IL-33, potentially consistent with levels in tissue microenvironments, synergize with IL-12 to induce secretion of additional cytokines, including tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). IL-33-induced activation of the p38 MAPK pathway in human NK cells is crucial for enhanced release of IFN-{gamma} and TNF in response to IL-12. Mechanistically, IL-33-induced p38 MAPK signaling enhances stability of IFNG transcripts and triggers ADAM17-mediated cleavage of TNF from the cell surface. These data support our hypothesis and suggest that altered sensitivity of NK cells to IL-12 in the presence of IL-33 may have important consequences in diseases associated with mixed cytokine milieus, like asthma and chronic obstructive pulmonary disease.  Graphical Abstract  O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=190 SRC=""FIGDIR/small/777847v2_ufig1.gif"" ALT=""Figure 1""> View larger version (40K): org.highwire.dtl.DTLVardef@c1f7c9org.highwire.dtl.DTLVardef@72d47dorg.highwire.dtl.DTLVardef@dc84d4org.highwire.dtl.DTLVardef@194b42f_HPS_FORMAT_FIGEXP  M_FIG C_FIG",2019-12-23,"Ohayon, D. E.; Ali, A.; Alarcon, P. C.; Krishnamurthy, D.; Kottyan, L.; Borchers, M.; Waggoner, S. N.",,,,True
48df5b06710467cbe5b41dd851e946fc936ecf15,biorxiv,Low basal expression and slow induction of IFITM3 puts immune cells at risk of influenza A infection,doi.org/10.1101/2019.12.20.885590,,,See https://www.biorxiv.org/about-biorxiv,"The interferon-induced transmembrane protein, IFITM3, has been shown to restrict influenza virus infection in murine and in vitro settings for ten years, but no explanation has been found to explain why this virus infection is so highly contagious and infects most individuals it comes in contact with. We confirm that the expression level of IFITM3 plays a role in determining the level of viral infection through manipulation of IFITM3 levels with interferon (IFN) stimulation and overexpression systems. Low basal expression may put some immune cells, including lymphocytes and lung-resident macrophages, at risk of influenza virus infection. Investigating the induction of IFITM3 by IFN, we find a strong preference for Type I IFN in IFITM3 induction in both cell lines and primary human cells. While myeloid cells can increase expression following stimulation by Type I IFN, lymphocytes show minimal induction of IFITM3 following IFN stimulation, suggesting that they are always at risk of viral infection. Surprisingly, we found that the time it takes for maximal induction of IFITM3 is relatively slow for an interferon-stimulated gene at around 36 hours. Low basal expression and slow induction of IFITM3 could increase the risk of influenza virus infection in selected immune cells.  ImportanceInfluenza virus infection remains one of the top ten threats to global health, causing significant deaths and hospitalisations across the world each year. Understanding mechanisms for controlling influenza virus infection remain a priority. The interferon-induced transmembrane protein IFITM3 can restrict influenza infection by limiting replication of the virus. The precise mechanisms of how IFITM3 reduced replication of influenza are unknown, although it is predicted to prevent release of viral contents into the cytosol by preventing pore formation on the endosomal compartments where it is suggested to reside. Here we have shown that the expression level of IFITM3 is important in determining the control of influenza virus infection. We find an expression pattern for IFITM3 that varies based on cell type, tissue locality, differentiation state and cell naivety, all of which highlights cells that may be at the highest risk of influenza infection.",2019-12-23,"Wellington, D.; Yin, Z.; Zhang, L.; Forbester, J. L.; Kite, K.; Laurenson-Schafer, H.; Makvandi-Nejad, S.; Jin, B.; Bowes, E.; Manoharan, K.; Maldonado-Perez, D.; Verrill, C.; Humphreys, I.; Dong, T.",,,,True
4602afcb8d95ebd9da583124384fd74299d20f5b,biorxiv,SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses,doi.org/10.1101/752592,,,See https://www.biorxiv.org/about-biorxiv,"Viruses possessing class I fusion proteins require proteolytic activation by host cell proteases to mediate fusion with the host cell membrane. The mammalian SPINT2 gene encodes a protease inhibitor that targets trypsin-like serine proteases. Here we show the protease inhibitor, SPINT2, restricts cleavage-activation efficiently for a range of influenza viruses and for human metapneumovirus (HMPV). SPINT2 treatment resulted in the cleavage and fusion inhibition of full-length influenza A/CA/04/09 (H1N1) HA, A/Aichi/68 (H3N2) HA, A/Shanghai/2/2013 (H7N9) HA and HMPV F when activated by trypsin, recombinant matriptase or KLK5. We also demonstrate that SPINT2 was able to reduce viral growth of influenza A/CA/04/09 H1N1 and A/X31 H3N2 in cell culture by inhibiting matriptase or TMPRSS2. Moreover, inhibition efficacy did not differ whether SPINT2 was added at the time of infection or 24 hours post-infection. Our data suggest that the SPINT2 inhibitor has a strong potential to serve as a novel broad-spectrum antiviral.",2020-01-06,"Straus, M.; Kinder, J. T.; Segall, M.; Dutch, R. E.; Whittaker, G. R.",,,,True
09c9fcabc66a106e01ef42247cbd86b6d85bd67f,biorxiv,Mono-ADP-ribosylation by ARTD10 restricts Chikungunya virus replication by interfering with the proteolytic activity of nsP2,doi.org/10.1101/2020.01.07.896977,,,See https://www.biorxiv.org/about-biorxiv,"A subset of intracellular mono-ADP-ribosyltransferases diphtheria toxin-like (ARTDs, aka mono-PARPs) is induced by type I interferons. Some of these mono-ARTDs feature antiviral activity while certain RNA viruses, including Chikungunya virus (CHIKV), encode mono-ADP-ribosylhydrolases, suggesting a role for mono-ADP-ribosylation (MARylation) in host-virus conflicts. CHIKV expresses four non-structural proteins (nsP1-nsP4), with nsP3 containing a macrodomain that hydrolyzes and thereby reverses protein MARylation in vitro and in cells. This de-MARylation activity is essential as hydrolase inactivating mutations result in replication defective virus. However, the substrates of MARylation during CHIKV infection are unknown and thus it is unclear how the macrodomain contributes to virus replication and how mono-ARTD-dependent MARylation confers antiviral immunity. We identified ARTD10 and ARTD12 as restriction factors for CHIKV replication in a catalytic activity-dependent manner. CHIKV replication requires processing of the non-structural polyprotein nsP1-4 by the nsP2-encoded protease and the assembly of the four individual nsPs into a functional replication complex. Expression of ARTD10 and ARTD12 resulted in a reduction of processed nsPs. Similarly, MAR hydrolase inactive CHIKV replicon mutants revealed a decrease in processed nsPs, comparable to an nsP2 protease defective mutant. This suggested that the macrodomain contributes to nsP2 protease activity. In support, a hydrolase-deficient virus was complemented by a protease-deficient virus. We hypothesized that MARylation regulates the proteolytic function of nsP2. Indeed, we found that nsP2 is MARylated by ARTD10. This inhibited nsP2 protease activity, thereby preventing polyprotein processing and consequently virus replication. This inhibition was antagonized by the MAR hydrolase activity of nsP3. Together, our findings provide a mechanistic explanation for the need of the viral MAR hydrolase for efficient replication of CHIKV.  Author SummaryInfectious diseases still pose major health threats. Especially fast evolving viruses find ever new strategies to manipulate the immune response. With climate warming and increased human mobility vector-borne pathogens like Chikungunya virus (CHIKV) spread and cause world-wide epidemics. Beyond the acute phase, CHIKV patients regularly suffer from chronic rheumatism. This entails a decline in life quality and an economic burden. To date no drugs are approved and the mode of pathogenesis remains elusive. Here we describe a mechanistic function of the CHIKV nsP3 macrodomain. We found that the viral nsP2 is mono-ADP-ribosylated interfering with its auto-proteolytic function. The nsP3 macrodomain removes this modification and restores the protease activity that is essential for replication. Because macrodomains are highly conserved they might represent broad antiviral targets.",2020-01-08,"Krieg, S.; Pott, F.; Eckei, L.; Verheirstaeten, M.; Buetepage, M.; Lippok, B.; Goffinet, C.; Luescher, B.; Verheugd, P.",,,,True
e18620d5cff022d18aa23da2fa4634331fa54860,biorxiv,Altered polarization of PAR-2 signaling during airway epithelial remodeling,doi.org/10.1101/2020.01.09.900555,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundProtease-activated receptor 2 (PAR-2) is activated by proteases involved in allergy and triggers airway epithelial secretion and inflammation. PAR-2 is normally expressed basolaterally in differentiated nasal ciliated cells.  ObjectiveWe tested if epithelial remodeling during diseases characterized by loss of cilia and squamous metaplasia may alter PAR-2 polarization.  MethodsEndogenous PAR-2 responses were measured by live cell calcium and cilia imaging, measurement of fluid secretion, and quantification of cytokines. We utilized airway squamous cell lines, primary differentiated air-liquid interface cultures, and tissue explants. Cells were exposed to disease-related modifiers that alter epithelial morphology, including IL-13, cigarette smoke condensate, and retinoic acid deficiency. We used concentrations and exposure times that altered epithelial morphology without causing breakdown of the epithelial barrier, likely reflecting early disease states.  ResultsPAR-2 signaling in airway squamous cells activated calcium and inflammatory responses. Squamous cells cultured at air liquid interface (ALI) responded to PAR-2 agonists applied both apically and basolaterally. Primary well-differentiated nasal epithelial ALI cultures responded only to basolateral PAR-2 stimulation. Primary cultures exposed to IL-13, cigarette smoke condensate, or reduced retinoic acid responded to both apical and basolateral PAR-2 stimulation. Nasal polyp tissue, but not control middle turbinate, exhibited apical calcium responses to PAR-2 stimulation. However, isolated ciliated cells from both polyp and turbinate maintained basolateral PAR-2 polarization.  ConclusionsSquamous metaplasia and/or loss of cilia enhances apical PAR-2 responses. Altered PAR-2 polarization in dedifferentiated or remodeled epithelia may contribute to increased sensitivity to inhaled protease allergens in inflammatory airway diseases.",2020-01-09,"Carey, R. M.; Freund, J. R.; Hariri, B. M.; Adappa, N. D.; Palmer, J. N.; Lee, R. J.",,,,True
b80d9de7750d627a0189fcd2dfd82c7efcb1c079,biorxiv,An interaction network of RNA-binding proteins involved in Drosophila oogenesis,doi.org/10.1101/2020.01.08.899146,,,See https://www.biorxiv.org/about-biorxiv,"During Drosophila oogenesis, the localization and translational regulation of maternal transcripts relies on RNA-binding proteins (RBPs). Many of these RBPs localize several mRNAs and may have additional direct interaction partners to regulate their functions. Using immunoprecipitation from whole Drosophila ovaries coupled to mass spectrometry, we examined protein-protein associations of 6 GFP-tagged RBPs expressed at physiological levels. Analysis of the interaction network and further validation in human cells allowed us to identify 26 previously unknown associations, besides recovering several well characterized interactions. We identified interactions between RBPs and several splicing factors, providing links between nuclear and cytoplasmic events of mRNA regulation. Additionally, components of the translational and RNA decay machineries were selectively co-purified with some baits, suggesting a mechanism for how RBPs may regulate maternal transcripts. Given the evolutionary conservation of the studied RBPs, the interaction network presented here provides the foundation for future functional and structural studies of mRNA localization across metazoans.",2020-01-09,"Bansal, P.; Madlung, J.; Schaaf, K.; Macek, B.; Bono, F.",,,,True
0015023cc06b5362d332b3baf348d11567ca2fbb,biorxiv,The RNA pseudoknots in foot-and-mouth disease virus are dispensable for genome replication but essential for the production of infectious virus.,doi.org/10.1101/2020.01.10.901801,,,See https://www.biorxiv.org/about-biorxiv,"The positive stranded RNA genomes of picornaviruses comprise a single large open reading frame flanked by 5' and 3' untranslated regions (UTRs). Foot-and-mouth disease virus (FMDV) has an unusually large 5' UTR (1.3 kb) containing five structural domains. These include the internal ribosome entry site (IRES), which facilitates initiation of translation, and the cis-acting replication element (cre). Less well characterised structures are a 5' terminal 360 nucleotide stem-loop, a variable length poly-C-tract of approximately 100-200 nucleotides and a series of two to four tandemly repeated pseudoknots (PKs). We investigated the structures of the PKs by selective 2' hydroxyl acetylation analysed by primer extension (SHAPE) analysis and determined their contribution to genome replication by mutation and deletion experiments. SHAPE and mutation experiments confirmed the importance of the previously predicted PK structures for their function. Deletion experiments showed that although PKs are not essential for replication, they provide genomes with a competitive advantage. However, although replicons and full-length genomes lacking all PKs were replication competent, no infectious virus was rescued from genomes containing less than one PK copy. This is consistent with our earlier report describing the presence of putative packaging signals in the PK region.",2020-01-11,"Ward, J. C. J.; Lasecka-Dykes, L.; Neil, C.; Adeyemi, O.; Gold, S.; McLean, N.; Wright, C.; Herod, M. R.; Kealy, D.; Warner, E.; King, D. P.; Tuthill, T. J.; Rowlands, D. J.; Stonehouse, N. J.",,,,True
7837a1b529936ac78b802e41daa73ddab8bfc41a,biorxiv,Cotranslational Folding Stimulates Programmed Ribosomal Frameshifting in the Alphavirus Structural Polyprotein,doi.org/10.1101/790444,,,See https://www.biorxiv.org/about-biorxiv,"Viruses maximize their genetic coding capacity through a variety of biochemical mechanisms including programmed ribosomal frameshifting (PRF), which facilitates the production of multiple proteins from a single transcript. PRF is typically stimulated by structural elements within the mRNA that generate mechanical tension between the transcript and ribosome. However, in this work we show that the forces generated by the cotranslational folding of the nascent polypeptide chain can also enhance PRF. Using an array of biochemical, cellular, and computational techniques, we first demonstrate that the Sindbis virus structural polyprotein forms two competing topological isomers during biosynthesis at the ribosome-translocon complex. We then show that the formation of one of these topological isomers is linked to PRF. Coarse-grained molecular dynamic simulations reveal that the translocon-mediated membrane integration of a transmembrane domain upstream from the ribosomal slip-site generates a force on the nascent polypeptide chain that scales with observed frameshifting. Together, our results demonstrate that cotranslational folding of this protein generates a tension that stimulates PRF. To our knowledge, this constitutes the first example in which the conformational state of the nascent chain has been linked to PRF. These findings raise the possibility that, in addition to RNA-mediated translational recoding, a variety of cotranslational folding and/ or binding events may also stimulate PRF.",2020-01-16,"Harrington, H. R.; Zimmer, M. H.; Chamness, L. M.; Nash, V.; Penn, W. D.; Miller, T. F.; Mukhopadhyay, S.; Schlebach, J. P.",,,,True
de3ae7971891058db2f4b36cd216531e6f533332,biorxiv,Crystal structure of the giant panda MHC class I complex: first insights into the viral peptide presentation profile in the bear family,doi.org/10.1101/2020.01.15.908608,,,See https://www.biorxiv.org/about-biorxiv,"The viral cytotoxic T lymphocyte (CTL) epitope peptides presented by classical MHC-I molecules require the assembly of a peptide-MHC-I-{beta}2m (aka pMHC-I) trimolecular complex for TCR recognition, which is the critical activation link for triggering antiviral T cell immunity. Ursidae includes 5 genera and 8 species; however, research on T cell immunology in this family, especially structural immunology, is lacking. In this study, the structure of the key trimolecular complex pMHC-1 (aka pAime-128), which binds a peptide from canine distemper virus, was solved for the first time using giant panda as a representative species of Ursidae. The structural characteristics of the giant panda pMHC-I complex, including the unique pockets in the peptide-binding groove (PBG), were analyzed in detail. Comparing the panda pMHC-I to others in the bear family and extending the comparison to other mammals revealed distinct features. The interaction between MHC-I and {beta}2m, the features of pAime-128 involved in TCR docking and CD8 binding, the anchor sites in the PBG, and the CTL epitopes of potential viruses that infect pandas were concretely clarified. Unique features of pMHC-I viral antigen presentation in the panda were revealed by solving the three-dimensional structure of pAime-128. The distinct characteristics of pAime-128 indicate an unusual event that emerged during the evolution of the MHC system in the bear family. These results provide a new platform for research on panda CTL immunity and the design of vaccines for application in the bear family.  IMPORTANCEUrsidae includes 5 genera and 8 species; however, the study of its immunology, especially structural immunology, is extremely rare to date. In this paper, we first crystallized the key complex pMHC-I, taking the giant panda as its representative species. Structural characteristics of the giant panda pMHC-I complexes, contains the unique pockets of PBG were analyzed in detail. Comparison of the panda pMHC-I in the bear family and other mammals, almost definite features was displayed. Meanwhile, the interaction between HC and LV, the unique features of pMHC-I in the CD8 binding and TCR docking, validation of anchor site in the PBG, and epitopes of potential viruses infected with the pandas, were concretely clarified. These unique characteristics of pMHC-I clearly indicate an unusual situation during the evolution of MHC molecules in the endangered pandas. These results also provide a novel platform for further study of panda T cell immunology and vaccines.",2020-01-16,"Yuan, H.; Ma, L.; Zhang, L.; Li, X.; Xia, C.",,,,True
f8e8a9c6f5662c1739be031e6134284ef08ea8b2,biorxiv,Programmable low-cost DNA-based platform for viral RNA detection,doi.org/10.1101/2020.01.12.902452,,,See https://www.biorxiv.org/about-biorxiv,"Viral detection is critical for controlling disease spread and progression. Recent emerging threats including the Zika and Ebola virus outbreaks highlight the cost and difficulty in responding rapidly. In low-resource areas, a key obstacle is quick and accurate detection of viruses near the point of care. To address these challenges, we develop a platform for low-cost and rapid detection of viral RNA with DNA nanoswitches designed to mechanically reconfigure in response to specific viruses. Using Zika virus as a model system, we show non-enzymatic detection of viral RNA to the attomole level, with selective and multiplexed detection between related viruses and viral strains. For clinical-level sensitivity in biological fluids, we paired the assay with a sample preparation step using either RNA extraction or isothermal pre-amplification. Our assay can be performed with minimal or no lab infrastructure, and is readily adaptable (with [~]24-hour development time) to detect other viruses. Given this versatility, we expect that further development and field implementation will improve our ability to detect emergent viral threats and ultimately limit their impact.",2020-01-16,"Zhou, L.; Chandrasekaran, A. R.; Punnoose, J. A.; Bonenfant, G.; Charles, S.; Levchenko, O.; Badu, P.; Cavaliere, C.; Pager, C. T.; Halvorsen, K.",,,,True
7bc87a77a7aba144248cfa3bc514541f09047edf,biorxiv,A new phylogenetic protocol: Dealing with model misspecification and confirmation bias in molecular phylogenetics,doi.org/10.1101/400648,,,See https://www.biorxiv.org/about-biorxiv,"Molecular phylogenetics plays a key role in comparative genomics and has an increasingly-significant impacts on science, industry, government, public health, and society. We posit that the current phylogenetic protocol is missing two critical steps, and that their absence allows model misspecification and confirmation bias to unduly influence our phylogenetic estimates. Based on the potential offered by well-established but under-used procedures (e.g., assessment of phylogenetic assumptions and tests of goodness-of-fit), we introduce a new phylogenetic protocol that will reduce confirmation bias and increase the accuracy of phylogenetic estimates.",2020-01-17,"Jermiin, L. S.; Catullo, R. A.; Holland, B. R.",,,,True
26cb6703ca72bf97887abbc29a40b1bd9d7890f4,biorxiv,Hotspots of aberrant enhancer activity in fibrolamellar carcinoma reveal molecular mechanisms of oncogenesis and intrinsic drug resistance,doi.org/10.1101/2020.01.18.911297,,,See https://www.biorxiv.org/about-biorxiv,"Fibrolamellar carcinoma (FLC) is a rare, therapeutically intractable liver cancer that disproportionately affects youth. Although FLC tumors exhibit a distinct gene expression profile, the causative transcriptional mechanisms remain unclear. Here we used chromatin run-on sequencing to discover approximately 7,000 enhancers and 141 enhancer hotspots activated in FLC relative to non-malignant liver. Detailed bioinformatic analyses revealed aberrant ERK/MEK signaling and candidate master transcriptional regulators. We also defined the genes most strongly associated with aberrant FLC enhancer activity, including CA12 and SLC16A14. Treatment of FLC cell models with inhibitors of CA12 or SLC16A14 independently reduced cell viability and/or significantly enhanced the effect of MEK inhibitor cobimetinib. These findings highlight new molecular targets for drug development as well as novel drug combination approaches.",2020-01-18,"Dinh, T. A.; Sritharan, R.; Smith, F. D.; Francisco, A. B.; Ma, R. K.; Bunaciu, R. P.; Kanke, M.; Danko, C. G.; Massa, A. P.; Scott, J. D.; Sethupathy, P.",,,,True
8b88d01563538e4abd29c3ba493c534af30664cc,biorxiv,A mathematical model for simulating the transmission of Wuhan novel Coronavirus,doi.org/10.1101/2020.01.19.911669,,,See https://www.biorxiv.org/about-biorxiv,"As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probable be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from a seafood market (reservoir) to people, we simplified the model as Reservoir-People transmission network model. The basic reproduction number (R0) was calculated from the RP model to assess the transmissibility of the 2019-nCoV.",2020-01-19,"Chen, T.; Rui, J.; Wang, Q.; Zhao, Z.; Cui, J.-A.; Yin, L.",,,,True
9a3de625119a83aa1401eeb297937d9605f0d1f1,biorxiv,In-silico immune cell deconvolution of the airway proteomes of infants with pneumonia reveals a link between reduced airway eosinophils and an increased risk of mortality,doi.org/10.1101/840090,,,See https://www.biorxiv.org/about-biorxiv,"RationalePneumonia is a leading cause of mortality in infants and young children. The mechanisms that lead to mortality in these children are poorly understood. Studies of the cellular immunology of the infant airway have traditionally been hindered by the limited sample volumes available from the young, frail children who are admitted to hospital with pneumonia. This is further compounded by the relatively low frequencies of certain immune cell phenotypes that are thought to be critical to the clinical outcome of pneumonia. To address this, we developed a novel in-silico deconvolution method for inferring the frequencies of immune cell phenotypes in the airway of children with different survival outcomes using proteomic data.  MethodsUsing high-resolution mass spectrometry, we identified > 1,000 proteins expressed in the airways of children who were admitted to hospital with clinical pneumonia. 61 of these children were discharged from hospital and survived for more than 365 days after discharge, while 19 died during admission. We used machine learning by random forest to derive protein features that could be used to deconvolve immune cell phenotypes in paediatric airway samples. We applied these phenotype-specific signatures to identify airway-resident immune cell phenotypes that were differentially enriched by survival status and validated the findings using a large retrospective pneumonia cohort.  Main ResultsWe identified immune-cell phenotype classification features for 33 immune cell types. Eosinophil-associated features were significantly elevated in airway samples obtained from pneumonia survivors and were downregulated in children who subsequently died. To confirm these results, we analyzed clinical parameters from >10,000 children who had been admitted with pneumonia in the previous 10 years. The results of this retrospective analysis mirrored airway deconvolution data and showed that survivors had significantly elevated eosinophils at admission compared to fatal pneumonia.  ConclusionsUsing a proteomics bioinformatics approach, we identify airway eosinophils as a critical factor for pneumonia survival in infants and young children.",2020-01-19,"Sande, C. J.; Waeni, J. M.; Njunge, J. M.; Mutunga, M. M.; Gicheru, E. T.; Kibinge, N. K.; Gwela, A.",,,,True
9daed5e675ac113d1939056dcebbb1f32ec0d7ec,biorxiv,"Functional assessment of cell entry and receptor usage for lineage B β-coronaviruses, including 2019-nCoV",doi.org/10.1101/2020.01.22.915660,,,See https://www.biorxiv.org/about-biorxiv,"Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS- CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these novel viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoonotic viral outbreak. Here we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent 2019-nCoV, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells and confirm that human ACE2 is the receptor for the recently emerging 2019-nCoV.",2020-01-22,"Letko, M. C.; Munster, V.",,,,True
8fb933125bbd196f327026b14ef373915339e034,biorxiv,"Genomic and protein structure modelling analysis depicts the origin and infectivity of 2019-nCoV, a new coronavirus which caused a pneumonia outbreak in Wuhan, China",doi.org/10.1101/2020.01.20.913368,,,See https://www.biorxiv.org/about-biorxiv,"Detailed genomic and structure-based analysis of a new coronavirus, namely 2019-nCoV, showed that the new virus is a new type of bat coronavirus and is genetically fairly distant from the human SARS coronavirus. Structure analysis of the spike (S) protein of this new virus showed that its S protein only binds weakly to the ACE2 receptor on human cells whereas the human SARS coronavirus exhibits strongly affinity to the ACE receptor. These findings suggest that the new virus does not readily transmit between humans and should theoretically not able to cause very serious human infection. These data are important to guide design of infection control policy and inform the public on the nature of threat imposed by 2019-nCov when results of direct laboratory tests on this virus are not expected to be available in the near future.",2020-01-22,"Dong, N.; Yang, X.; Chen, K.; Chan, E.; Yang, M.; Chen, S.",,,,False
1e568acef94f2e99d551ec531a97373caac8a955,biorxiv,Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin,doi.org/10.1101/2020.01.22.914952,,,See https://www.biorxiv.org/about-biorxiv,"Since the SARS outbreak 18 years ago, a large number of severe acute respiratory syndrome related coronaviruses (SARSr-CoV) have been discovered in their natural reservoir host, bats1-4. Previous studies indicated that some of those bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a novel coronavirus (nCoV-2019) which caused an epidemic of acute respiratory syndrome in humans, in Wuhan, China. The epidemic, started from December 12th, 2019, has caused 198 laboratory confirmed infections with three fatal cases by January 20th, 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that nCoV-2019 is 96% identical at the whole genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV. The nCoV-2019 virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, we have confirmed that this novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.",2020-01-23,"Zhou, P.; Yang, X.-L.; Wang, X.-G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.-R.; Zhu, Y.; Li, B.; Huang, C.-L.; Chen, H.-D.; Chen, J.; Luo, Y.; Guo, H.; Jiang, R.-D.; Liu, M.-Q.; Chen, Y.; Shen, X.-R.; Wang, X.; Zheng, X.-S.; Zhao, K.; Chen, Q.-J.; Deng, F.; Liu, L.-L.; Yan, B.; Zhan, F.-X.; Wang, Y.-Y.; Xiao, G.; Shi, Z.-L.",,,,False
403d885a33958731c4607ea632453e25a89e2b57,biorxiv,Novel ionophores active against La Crosse virus identified through rapid antiviral screening,doi.org/10.1101/2020.01.21.914929,,,See https://www.biorxiv.org/about-biorxiv,"Bunyaviruses are significant human pathogens, causing diseases ranging from hemorrhagic fevers to encephalitis. Among these viruses, La Crosse virus (LACV), a member of the California serogroup, circulates in the eastern and midwestern United States. While LACV infection is often asymptomatic, dozens of cases of encephalitis are reported yearly. Unfortunately, no antivirals have been approved to treat LACV infection. Here, we developed a method to rapidly test potential antivirals against LACV infection. From this screen, we identified several potential antiviral molecules, including known antivirals. Additionally, we identified many novel antivirals that exhibited antiviral activity without affecting cellular viability. Valinomycin, a potassium ionophore, was among our top targets. We found that valinomycin exhibited potent anti-LACV activity in multiple cell types in a dose-dependent manner. Valinomycin did not affect particle stability or infectivity, suggesting that it may preclude virus replication by altering cellular potassium ions, a known determinant of LACV entry. We extended these results to other ionophores and found that the antiviral activity of valinomycin extended to other viral families including bunyaviruses (Rift Valley fever virus, Keystone virus), enteroviruses (Coxsackievirus, rhinovirus), flavirivuses (Zika), and coronaviruses (229E and MERS-CoV). In all viral infections, we observed significant reductions in virus titer in valinomycin-treated cells. In sum, we demonstrate the importance of potassium ions to virus infection, suggesting a potential therapeutic target to disrupt virus replication.  ImportanceNo antivirals are approved for the treatment of bunyavirus infection. The ability to rapidly screen compounds and identify novel antivirals is one means to accelerate drug discovery for viruses with no approved treatments. We used this approach to screen hundreds of compounds against La Crosse virus, an emerging bunyavirus that causes significant disease, including encephalitis. We identified several known and previously unidentified antivirals. We focused on a potassium ionophore, valinomycin, due to its promising in vitro antiviral activity. We demonstrate that valinomycin, as well as a selection of other ionophores, exhibits activity against La Crosse virus as well as several other distantly related bunyaviruses. We finally observe that valinomycin has activity against a wide array of human viral pathogens, suggesting that disrupting potassium ion homeostasis with valinomycin may be a potent host pathway to target to quell virus infection.",2020-01-23,"Sandler, Z. J.; Vu, M. N.; Menachery, V. D.; Mounce, B. C.",,,,True
e4cb4af2f4ec6f023096afcf7b3d4410584e1393,biorxiv,Designing Effective small interfering RNA for Post-Transcriptional Silencing of Human GREM1: A Comprehensive Bioinformatics Approach,doi.org/10.1101/2020.01.23.917559,,,See https://www.biorxiv.org/about-biorxiv,"Human gremlin-1 is a physiologically versatile signaling molecule that has been associated with several human diseases including cancer. The ability of gremlin-1 to induce fibrosis in organs and transduce angiogenesis makes it a target for cancer therapy. RNAi-based therapy has proven to be very efficient and specific in tumor growth inhibition. The efficacy and specificity of siRNA-mediated gene silencing depends on the designing approaches. Here, empirical guidelines for siRNA design and comprehensive target site availability analysis were used to select effective siRNA from a plethora of potential candidates designed using several computation algorithms. Then, the selected siRNA candidates were subjected to stringent similarity searches in order to obtain siRNA candidates with reduced off-target effects (high specificity). The best candidates were compared to experimentally successful gremlin-1 siRNAs in order to predict the silencing potency of the selected siRNAs. siRNA-6 (sense strand: 5-CCAAGAAAUUCACUACCAU-3), siRNA-7 (sense strand: 5-CCAUGAUGGUCACACUCAA-3) and siRNA-47 (sense strand: 5-GGCCCAGCACAAUGACUCA-3) were predicted to be highly effective siRNA candidates for gremlin-1 silencing. These siRNAs can be considered for RNAi-based therapy because off-target effects are predicted to be minimal.",2020-01-24,"ASIEDU, E.",,,,True
671b44ae9bec89cacf7ae9e7b2a79649a9b66773,biorxiv,Pattern of early human-to-human transmission of Wuhan 2019-nCoV,doi.org/10.1101/2020.01.23.917351,,,See https://www.biorxiv.org/about-biorxiv,"On December 31, 2019, the World Health Organization was notified about a cluster of pneumonia of unknown aetiology in the city of Wuhan, China. Chinese authorities later identified a new coronavirus (2019-nCoV) as the causative agent of the outbreak. As of January 23, 2020, 655 cases have been confirmed in China and several other countries. Understanding the transmission characteristics and the potential for sustained human-to-human transmission of 2019-nCoV is critically important for coordinating current screening and containment strategies, and determining whether the outbreak constitutes a public health emergency of international concern (PHEIC). We performed stochastic simulations of early outbreak trajectories that are consistent with the epidemiological findings to date. We found the basic reproduction number, R0, to be around 2.2 (90% high density interval 1.4--3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of a similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and the 1918 pandemic influenza. These findings underline the importance of heightened screening, surveillance and control efforts, particularly at airports and other travel hubs, in order to prevent further international spread of 2019-nCoV.",2020-01-24,"Riou, J.; Althaus, C. L.",,,,True
4b8bdaf9670d7c24f952ca38bfe6c699152421b7,biorxiv,Predicting the global mammalian viral sharing network using phylogeography,doi.org/10.1101/732255,,,See https://www.biorxiv.org/about-biorxiv,"Understanding interspecific viral transmission is key to understanding viral ecology and evolution, disease spillover into humans, and the consequences of global change. Prior work has demonstrated that macroecological factors drive viral sharing in some mammalian groups, but analyses have never attempted to predict viral sharing in a pan-mammalian context. Here we show that host phylogenetic similarity and geographic range overlap are strong, nonlinear predictors of viral sharing among species across the entire mammal class. Using these traits, we predict global viral sharing patterns across 4196 mammal species and show that our simulated network successfully predicts viral sharing and reservoir host status using internal validation and an external dataset. We predict high rates of mammalian viral sharing in the tropics, particularly among rodents and bats, and that within- and between-order sharing differs geographically and taxonomically. Our results emphasize the importance of macroecological factors in shaping mammalian viral communities, and provide a robust, general model to predict viral host range and guide pathogen surveillance and conservation efforts.",2020-01-24,"Albery, G. F.; Eskew, E. A.; Ross, N.; Olival, K. J.",,,,True
a3116a1ea2e157c8855023d968cc0f0bd6c9846f,biorxiv,The 2019-new Coronavirus epidemic: evidence for virus evolution,doi.org/10.1101/2020.01.24.915157,,,See https://www.biorxiv.org/about-biorxiv,"There is concern about a new coronavirus, the 2019-nCoV, as a global public health threat. In this article, we provide a preliminary evolutionary and molecular epidemiological analysis of this new virus. A phylogenetic tree has been built using the 15 available whole genome sequence of 2019-nCoV and 12 whole genome sequences highly similar sequences available in gene bank (5 from SARS, 2 from MERS and 5 from Bat SARS-like Coronavirus). FUBAR analysis shows that the Nucleocapsid and the Spike Glycoprotein has some sites under positive pressure while homology modelling helped to explain some molecular and structural differences between the viruses. The phylogenetic tree showed that 2019.nCoV significantly clustered with Bat SARS-like Coronavirus sequence isolated in 2015, whereas structural analysis revealed mutation in S and nucleocapsid proteins. From these results, 2019nCoV could be considered a coronavirus distinct from SARS virus, probably transmitted from bats or another host where mutations conferred upon it the ability to infect humans.",2020-01-24,"Benvenuto, D.; Giovanetti, M.; Ciccozzi, A.; Spoto, S.; Angeletti, S.; Ciccozzi, M.",,,,True
b6e92eda6c26b456165422d4e5552b81754c4a82,biorxiv,2019-20 Wuhan coronavirus outbreak: Intense surveillance is vital for preventing sustained transmission in new locations,doi.org/10.1101/2020.01.24.919159,,,See https://www.biorxiv.org/about-biorxiv,"The outbreak of pneumonia originating in Wuhan, China, has generated 830 confirmed cases, including 26 deaths, as of 24 January 2020. The virus (2019-nCoV) has spread elsewhere in China and to other countries, including South Korea, Thailand, Japan and USA. Fortunately, there has not yet been evidence of sustained human-to-human transmission outside of China. Here we assess the risk of sustained transmission whenever the coronavirus arrives in other countries. Data describing the times from symptom onset to hospitalisation for 47 patients infected in the current outbreak are used to generate an estimate for the probability that an imported case is followed by sustained human-to-human transmission. Under the assumptions that the imported case is representative of the patients in China, and that the 2019-nCoV is similarly transmissible to the SARS coronavirus, the probability that an imported case is followed by sustained human-to-human transmission is 0.37. However, if the mean time from symptom onset to hospitalisation can be halved by intense surveillance, then the probability that an imported case leads to sustained transmission is only 0.005. This emphasises the importance of current surveillance efforts in countries around the world, to ensure that the ongoing outbreak will not become a large global epidemic.",2020-01-25,"Thompson, R. N.",,,,True
fe66306680e5be9820e2cc3742b663a782eb1b31,biorxiv,Modelling the epidemic trend of the 2019 novel coronavirus outbreak in China,doi.org/10.1101/2020.01.23.916726,,,See https://www.biorxiv.org/about-biorxiv,"We present a timely evaluation of the Chinese 2019-nCov epidemic in its initial phase, where 2019-nCov demonstrates comparable transmissibility but lower fatality rates than SARS and MERS. A quick diagnosis that leads to case isolation and integrated interventions will have a major impact on its future trend. Nevertheless, as China is facing its Spring Festival travel rush and the epidemic has spread beyond its borders, further investigation on its potential spatiotemporal transmission pattern and novel intervention strategies are warranted.",2020-01-25,"Shen, M.; Peng, Z.; Xiao, Y.; Zhang, L.",,,,True
e29b287d326be9c2c0a7dcd7a81cb49cc2125360,biorxiv,Under-the-radar dengue virus infections in natural populations of Aedes aegypti mosquitoes,doi.org/10.1101/2020.01.24.919282,,,See https://www.biorxiv.org/about-biorxiv,"The incidence of locally acquired dengue infections increased during the last decade in the United States, compelling a sustained research effort on the dengue mosquito vector, Aedes aegypti, and its microbiome, which has been shown to influence virus transmission success. We examined the  metavirome of four populations of Ae. aegypti mosquitoes collected in 2016-2017 from Manatee County, Florida. Unexpectedly, we discovered that dengue virus serotype 4 (DENV4) was circulating in these mosquito populations, representing the first documented case of such a phenomenon in the absence of a local DENV4 human case in this county over a two-year period. We confirmed that all of the mosquito populations carried the same DENV4 strain, assembled its full genome, validated infection orthogonally by reverse transcriptase PCR, traced the virus origin, estimated the time period of its introduction to the Caribbean region, as well as explored the viral genetic signatures and mosquito-specific virome associations that potentially mediated DENV4 persistence in mosquitoes. We discuss the significance of prolonged maintenance of these DENV4 infections in Ae. aegypti that occurred in the absence of a DENV4 human index case in Manatee County with respect to the inability of current surveillance paradigms to detect mosquito vector infections prior to a potential local outbreak.  ImportanceSince 1999, dengue outbreaks in the continental United States (U.S.) involving local transmission have occurred episodically and only in Florida and Texas. In Florida, these episodes appear to be coincident with increased introductions of dengue virus into the region through human travel and migration from endemic countries. To date, the U.S. public health response to dengue outbreaks is largely reactive, and implementation of comprehensive arbovirus surveillance in advance of predictable transmission seasons, which would enable proactive preventative efforts, remains unsupported. The significance of our finding is that it is the first documented report of non-outbreak DENV4 transmission and maintenance within a local mosquito vector population in the continental U.S.in the absence of a human case during a two-year time period. Our data suggest that molecular surveillance of mosquito populations in high-risk, high tourism areas of the U.S., may allow for proactive, targeted vector control before potential arbovirus outbreaks.",2020-01-25,"Boyles, S. M.; Mavian, C. N.; Finol, E.; Ukhanova, M.; Stephenson, C. J.; Hamerlinck, G.; Kang, S.; Baumgartner, C.; Geesey, M.; Stinton, I.; Williams, K.; Mathias, D. K.; Prosperi, M.; Mai, V.; Salemi, M.; Buckner, E. A.; Lednicky, J. A.; Rivers, A. R.; Dinglasan, R. R.",,,,True
68e509d42a7d3349550512d80eca4e2b2123613f,biorxiv,"Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov",doi.org/10.1101/2020.01.26.919985,,,See https://www.biorxiv.org/about-biorxiv,"A novel coronavirus (2019-nCov) was identified in Wuhan, Hubei Province, China in December of 2019. This new coronavirus has resulted in thousands of cases of lethal disease in China, with additional patients being identified in a rapidly growing number internationally. 2019-nCov was reported to share the same receptor, Angiotensin-converting enzyme 2 (ACE2), with SARS-Cov. Here based on the public database and the state-of-the-art single-cell RNA-Seq technique, we analyzed the ACE2 RNA expression profile in the normal human lungs. The result indicates that the ACE2 virus receptor expression is concentrated in a small population of type II alveolar cells (AT2). Surprisingly, we found that this population of ACE2-expressing AT2 also highly expressed many other genes that positively regulating viral reproduction and transmission. A comparison between eight individual samples demonstrated that the Asian male one has an extremely large number of ACE2-expressing cells in the lung. This study provides a biological background for the epidemic investigation of the 2019-nCov infection disease, and could be informative for future anti-ACE2 therapeutic strategy development.",2020-01-26,"Zhao, Y.; Zhao, Z.; Wang, Y.; Zhou, Y.; Ma, Y.; Zuo, W.",,,,True
33709ad4554cfe57440d6186720cbbc56821f18a,biorxiv,Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event,doi.org/10.1101/2020.01.26.920249,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundA novel coronavirus (2019-nCoV) associated with human to human transmission and severe human infection has been recently reported from the city of Wuhan in China. Our objectives were to characterize the genetic relationships of the 2019-nCoV and to search for putative recombination within the subgenus of sarbecovirus.  MethodsPutative recombination was investigated by RDP4 and Simplot v3.5.1 and discordant phylogenetic clustering in individual genomic fragments was confirmed by phylogenetic analysis using maximum likelihood and Bayesian methods.  ResultsOur analysis suggests that the 2019-nCoV although closely related to BatCoV RaTG13 sequence throughout the genome (sequence similarity 96.3%), shows discordant clustering with the Bat-SARS-like coronavirus sequences. Specifically, in the 5-part spanning the first 11,498 nucleotides and the last 3-part spanning 24,341-30,696 positions, 2019-nCoV and RaTG13 formed a single cluster with Bat-SARS-like coronavirus sequences, whereas in the middle region spanning the 3-end of ORF1a, the ORF1b and almost half of the spike regions, 2019-nCoV and RaTG13 grouped in a separate distant lineage within the sarbecovirus branch.  ConclusionsThe levels of genetic similarity between the 2019-nCoV and RaTG13 suggest that the latter does not provide the exact variant that caused the outbreak in humans, but the hypothesis that 2019-nCoV has originated from bats is very likely. We show evidence that the novel coronavirus (2019-nCov) is not-mosaic consisting in almost half of its genome of a distinct lineage within the betacoronavirus. These genomic features and their potential association with virus characteristics and virulence in humans need further attention.",2020-01-27,"Paraskevis, D.; Kostaki, E. G.; Magiorkinis, G.; Panayiotakopoulos, G.; Tsiodras, S.",,,,False
f24d3b4b4af138be06b7452b7acefc8948bc1056,biorxiv,Beware of asymptomatic transmission: Study on 2019-nCoV prevention and control measures based on extended SEIR model,doi.org/10.1101/2020.01.28.923169,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundThe 2019 new coronavirus, ""2019-nCoV"", was discovered from Wuhan Viral Pneumonia cases in December 2019, and was named by the World Health Organization on January 12, 2020. In the early stage, people knows little about the 2019-nCoV virus was not clear, and the spread period was encountering Chinas annual spring migration, which made the epidemic spread rapidly from Wuhan to almost all provinces in China.  MethodsThis study builds a SEIRD model that considers the movement of people across regions, revealing the effects of three measures on controlling the spread of the epidemic.Based on MATLAB R2017a, computational experiments were performed to simulate the epidemic prevention and control measures.  FindingsThe research results show that current prevention and control measures in China are very necessary. This study further validates the concerns of international and domestic experts regarding asymptomatic transmission (E-status).  InterpretationThe results of this study are applicable to explore the impact of the implementation of relevant measures on the prevention and control of epidemic spread, and to identify key individuals that may exist during the spread of the epidemic.",2020-01-28,"Shao, P.; Shan, Y.",,,,True
aef0734eb2538d3624d650a4ae20c3f66cace5f2,biorxiv,Chronic hM3Dq signaling in microglia ameliorates neuroinflammation in male mice,doi.org/10.1101/2020.01.27.921809,,,See https://www.biorxiv.org/about-biorxiv,"Microglia express muscarinic G protein-coupled receptors (GPCRs) that sense cholinergic activity and are activated by acetylcholine to potentially regulate microglial functions. Knowledge about how distinct types of muscarinic GPCR signaling regulate microglia function in vitro and in vivo is still poor, partly due to the fact that some of these receptors are also present in astrocytes and neurons. We generated mice expressing the hM3Dq Designer Receptor Exclusively Activated by Designer Drugs (DREADD) selectively in microglia to investigate the role of muscarinic M3Gq-linked signaling. We show that activation of hM3Dq using clozapine N-oxide (CNO) elevated intracellular calcium levels and increased phagocytosis of FluoSpheres in vitro. Acute treatment with CNO in vivo did not affect male mouse behavior, however chronic CNO treatment decreased sickness behavior triggered by lipopolysaccharide (LPS) treatment. Interestingly, whereas acute treatment with CNO increased synthesis of cytokine mRNA, chronic treatment attenuated LPS-induced cytokine mRNA changes in the brain, likely explaining the improvement in sickness behavior by chronic hM3Dq activation. No effect of CNO was observed in DREADD-negative mice. These results suggest that chronic activation of M3 muscarinic receptors (the hM3Dq progenitor) in microglia, and potentially other Gq-coupled GPCRs, preconditions microglia to decrease their response to further immunological challenges. Our results indicate that hM3Dq can be a useful tool to modulate neuroinflammation and study microglial immunological memory in vivo, which may be applicable for manipulations of neuroinflammation in neurodegenerative and psychiatric diseases.  HighlightsO_LIMicroglial function was manipulated by specific activation of hM3Dq signaling. C_LIO_LIChronic hM3Dq activation prevented LPS-induced sickness behavior in mice. C_LIO_LIMicroglial hM3Dq signaling modulated expression of pro-inflammatory cytokines. C_LI",2020-01-28,"Binning, W.; Hogan-Cann, A. E.; Sakae, D. Y.; Maksoud, M.; Ostapchenko, V.; Al-Onaizi, M.; Matovic, S.; Lu, W.-Y.; Prado, M. A. M.; Inoue, W.; Prado, V. F.",,,,True
c12ecbc6d4b78c0026cae06984d00a2fc7da3bc8,biorxiv,From SARS-CoV to Wuhan 2019-nCoV Outbreak: Similarity of Early Epidemic and Prediction of Future Trends,doi.org/10.1101/2020.01.24.919241,,,See https://www.biorxiv.org/about-biorxiv,"This manuscript has been withdrawn as it was submitted without the full consent of all the authors. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.",2020-01-28,"Chen, Z.; Zhang, W.; Lu, Y.; Guo, C.; Guo, Z.; Liao, C.; Zhang, X.; Zhang, Y.; Han, X.; Li, Q.; Lipkin, W. I.; Lu, J.",,,,False
06a1002f9fbea7179ac3572843f66b14568af6e4,biorxiv,"Nelfinavir was predicted to be a potential inhibitor of 2019 nCov main protease by an integrative approach combining homology modelling, molecular docking and binding free energy calculation",doi.org/10.1101/2020.01.27.921627,,,See https://www.biorxiv.org/about-biorxiv,"2019-nCov has caused more than 80 deaths as of 27 January 2020 in China, and infection cases have been reported in more than 10 countries. However, there is no approved drug to treat the disease. 2019-nCov Mpro is a potential drug target to combat the virus. We built homology models based on SARS Mpro structures, and docked 1903 small molecule drugs to the models. Based on the docking score and the 3D similarity of the binding mode to the known Mpro ligands, 4 drugs were selected for binding free energy calculations. Both MM/GBSA and SIE methods voted for nelfinavir, with the binding free energy of -24.69{+/-}0.52 kcal/mol and -9.42{+/-}0.04 kcal/mol, respectively. Therefore, we suggested that nelfinavir might be a potential inhibitor against 2019-nCov Mpro.",2020-01-28,"Xu, Z.; Peng, C.; Shi, Y.; Zhu, Z.; Mu, K.; Wang, X.; Zhu, W.",,,,True
256825e13de92e437384b7b3b88429bffebdcae5,biorxiv,Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody,doi.org/10.1101/2020.01.28.923011,,,See https://www.biorxiv.org/about-biorxiv,"The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 800 laboratory-confirmed human infections, including 25 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS-CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. Therefore, CR3022 has the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g., m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, indicating that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.",2020-01-28,"Tian, X.; Li, C.; Huang, A.; Xia, S.; Lu, S.; Shi, Z.; Lu, L.; Jiang, S.; Yang, Z.; Wu, Y.; Ying, T.",,,,False
029c1c588047f1d612a219ee15494d2d19ff7439,biorxiv,Protective Population Behavior Change in Outbreaks of Emerging Infectious Disease,doi.org/10.1101/2020.01.27.921536,,,See https://www.biorxiv.org/about-biorxiv,"During outbreaks of emerging infections, the lack of effective drugs and vaccines increases reliance on non-pharmacologic public health interventions and behavior change to limit human-to-human transmission. Interventions that increase the speed with which infected individuals remove themselves from the susceptible population are paramount, particularly isolation and hospitalization. Ebola virus disease (EVD), Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory Syndrome (MERS) are zoonotic viruses that have caused significant recent outbreaks with sustained human-to-human transmission. This investigation quantified changing mean removal rates (MRR) and days from symptom onset to hospitalization (DSOH) of infected individuals from the population in seven different outbreaks of EVD, SARS, and MERS, to test for statistically significant differences in these metrics between outbreaks. We found that epidemic week and viral serial interval were correlated with the speed with which populations developed and maintained health behaviors in each outbreak.",2020-01-28,"Lodge, E. K.; Schatz, A. M.; Drake, J. M.",,,,True
d49f8ba7212183bc1b7f2cb6dd709dd197303b3d,biorxiv,Spreading predictability in complex networks,doi.org/10.1101/2020.01.28.922757,,,See https://www.biorxiv.org/about-biorxiv,"Spreading dynamics analysis is an important and interesting topic since it has many applications such as rumor or disease controlling, viral marketing and information recommending. Many state-of-the-art researches focus on predicting infection scale or threshold. Few researchers pay attention to the predicting of infection nodes from a snapshot. With developing of precision marketing, recommending and, controlling, how to predict infection nodes precisely from snapshot becomes a key issue in spreading dynamics analysis. In this paper, a probability based prediction model is presented so as to estimate the infection nodes from a snapshot of spreading. Experimental results on synthetic and real networks demonstrate that the model proposed could predict the infection nodes precisely in the sense of probability.",2020-01-28,"Chen, D.-B.; Zhao, N.; Wang, J.; Yu, Y.; Zhao, J.",,,,True
c04c7fb330a409a00f67040dde0f83b3da88eacb,biorxiv,Potential inhibitors for 2019-nCoV coronavirus M protease from clinically approved medicines,doi.org/10.1101/2020.01.29.924100,,,See https://www.biorxiv.org/about-biorxiv,"Starting from December 2019, a novel coronavirus, named 2019-nCoV, was found to cause Severe Acute Respiratory (SARI) symptoms and rapid pandemic in China. With the hope to identify candidate drugs for 2019-nCoV, we adopted a computational approach to screen for available commercial medicines which may function as inhibitors for the Mpro of 2019-nCoV. Up to 10 commercial medicines that may form hydrogen bounds to key residues within the binding pocket of 2019-nCoV Mpro were identified, which may have higher mutation tolerance than lopinavir/ritonavir and may also function as inhibitors for other coronaviruses with similar Mpro binding sites and pocket structures.",2020-01-29,"Liu, X.; Wang, X.-J.",,,,True
24ff82a421f1a33db3ebaa22652bd62e0cb77c57,biorxiv,"Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: A data-driven analysis in the early phase of the outbreak",doi.org/10.1101/2020.01.23.916395,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundsAn ongoing outbreak of a novel coronavirus (2019-nCoV) pneumonia hit a major city of China, Wuhan, December 2019 and subsequently reached other provinces/regions of China and countries. We present estimates of the basic reproduction number, R0, of 2019-nCoV in the early phase of the outbreak.  MethodsAccounting for the impact of the variations in disease reporting rate, we modelled the epidemic curve of 2019-nCoV cases time series, in mainland China from January 10 to January 24, 2020, through the exponential growth. With the estimated intrinsic growth rate ({gamma}), we estimated R0 by using the serial intervals (SI) of two other well-known coronavirus diseases, MERS and SARS, as approximations for the true unknown SI.  FindingsThe early outbreak data largely follows the exponential growth. We estimated that the mean R0 ranges from 2.24 (95%CI: 1.96-2.55) to 3.58 (95%CI: 2.89-4.39) associated with 8-fold to 2-fold increase in the reporting rate. We demonstrated that changes in reporting rate substantially affect estimates of R0.  ConclusionThe mean estimate of R0 for the 2019-nCoV ranges from 2.24 to 3.58, and significantly larger than 1. Our findings indicate the potential of 2019-nCoV to cause outbreaks.",2020-01-29,"Zhao, S.; Lin, Q.; Ran, J.; MUSA, S. S.; Yang, G.; Wang, W.; Lou, Y.; Gao, D.; Yang, L.; He, D.; Wang, M. H.",,,,True
754315299d847600d6c5d414665c728d40bf731d,biorxiv,"Breaking down of healthcare system: Mathematical modelling for controlling the novel coronavirus (2019-nCoV) outbreak in Wuhan, China",doi.org/10.1101/2020.01.27.922443,,,See https://www.biorxiv.org/about-biorxiv,"A novel coronavirus pneumonia initially identified in Wuhan, China and provisionally named 2019-nCoV has surged in the public. In anticipation of substantial burdens on healthcare system following this human-to-human spread, we aim to scrutinise the currently available information and evaluate the burden of healthcare systems during this outbreak in Wuhan. We applied a modified SIR model to project the actual number of infected cases and the specific burdens on isolation wards and intensive care units, given the scenarios of different diagnosis rates as well as different public health intervention efficacy. Our estimates suggest the actual number of infected cases could be much higher than the reported, with estimated 26,701 cases (as of 28th January 2020) assuming 50% diagnosis rate if no public health interventions were implemented. The estimated burdens on healthcare system could be largely reduced if at least 70% efficacy of public health intervention is achieved.",2020-01-30,"Ming, W.-k.; Huang, J.; Zhang, C. J. P.",,,,True
18dc6a67045d2687d2b5c11c85797f42824ed243,biorxiv,Evolution and variation of 2019-novel coronavirus,doi.org/10.1101/2020.01.30.926477,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundThe current outbreak caused by novel coronavirus (2019-nCoV) in China has become a worldwide concern. As of 28 January 2020, there were 4631 confirmed cases and 106 deaths, and 11 countries or regions were affected.  MethodsWe downloaded the genomes of 2019-nCoVs and similar isolates from the Global Initiative on Sharing Avian Influenza Database (GISAID and nucleotide database of the National Center for Biotechnology Information (NCBI). Lasergene 7.0 and MEGA 6.0 softwares were used to calculate genetic distances of the sequences, to construct phylogenetic trees, and to align amino acid sequences. Bayesian coalescent phylogenetic analysis, implemented in the BEAST software package, was used to calculate the molecular clock related characteristics such as the nucleotide substitution rate and the most recent common ancestor (tMRCA) of 2019-nCoVs.  ResultsAn isolate numbered EPI_ISL_403928 showed different phylogenetic trees and genetic distances of the whole length genome, the coding sequences (CDS) of ployprotein (P), spike protein (S), and nucleoprotein (N) from other 2019-nCoVs. There are 22, 4, 2 variations in P, S, and N at the level of amino acid residues. The nucleotide substitution rates from high to low are 1{middle dot}05 x 10-2 (nucleotide substitutions/site/year, with 95% HPD interval being 6.27 x 10-4 to 2.72 x 10-2) for N, 5.34 x 10-3 (5.10 x 10-4, 1.28 x 10-2) for S, 1.69 x 10-3 (3.94 x 10-4, 3.60 x 10-3) for P, 1.65 x 10-3 (4.47 x 10-4, 3.24 x 10-3) for the whole genome, respectively. At this nucleotide substitution rate, the most recent common ancestor (tMRCA) of 2019-nCoVs appeared about 0.253-0.594 year before the epidemic.  ConclusionOur analysis suggests that at least two different viral strains of 2019-nCoV are involved in this outbreak that might occur a few months earlier before it was officially reported.",2020-01-30,"Xiong, C.; Jiang, L.; Chen, Y.; Jiang, Q.",,,,True
c6ec1380338cb2467dc6fc14add09ca5bea18411,biorxiv,Therapeutic Drugs Targeting 2019-nCoV Main Protease by High-Throughput Screening,doi.org/10.1101/2020.01.28.922922,,,See https://www.biorxiv.org/about-biorxiv,"2019 Novel Coronavirus (2019-nCoV) is a virus identified as the cause of the outbreak of pneumonia first detected in Wuhan, China. Investigations on the transmissibility, severity, and other features associated with this virus are ongoing. Currently, there is no vaccine or therapeutic antibody to prevent the infection, and more time is required to develop an effective immune strategy against the pathogen. In contrast, specific inhibitors targeting the key protease involved in replication and proliferation of the virus are the most effective means to alleviate the epidemic. The main protease of SARS-CoV is essential for the life cycle of the virus, which showed 96.1% of similarity with the main proteaseof 2019-nCoV, is considered to be an attractive target for drug development. In this study, we have identified 4 small molecular drugs with high binding capacity with SARS-CoV main protease by high-throughput screening based on the 8,000 clinical drug libraries, all these drugs have been widely used in clinical applications with guaranteed safety, which may serve as promising candidates to treat the infection of 2019-nCoV.",2020-01-30,"Li, Y.; Zhang, J.; Wang, N.; Li, H.; Shi, Y.; Guo, G.; Liu, K.; Zeng, H.; Zou, Q.",,,,True
5cc8ba9049730b71663a2208d37f873722abc707,biorxiv,Engineered unnatural ubiquitin for optimal detection of deubiquitinating enzymes,doi.org/10.1101/2020.01.30.926881,,,See https://www.biorxiv.org/about-biorxiv,"Deubiquitinating enzymes (DUBs) are responsible for removing ubiquitin (Ub) from its protein conjugates. DUBs have been implicated as attractive therapeutic targets in the treatment of viral diseases, neurodegenerative disorders and cancer. The lack of selective chemical tools for the exploration of these enzymes significantly impairs the determination of their roles in both normal and pathological states. Commercially available fluorogenic substrates are based on the C-terminal Ub motif or contain Ub coupled to a fluorophore (Z-LRGG-AMC, Ub-AMC); therefore, these substrates suffer from lack of selectivity. By using a hybrid combinatorial substrate library (HyCoSuL) and a defined P2 library containing a wide variety of nonproteinogenic amino acids, we established a full substrate specificity profile for two DUBs--MERS PLpro and human UCH-L3. Based on these results, we designed and synthesized Ub-based substrates and activity-based probes (ABPs) containing selected unnatural amino acids located in the C-terminal Ub motif. Biochemical analysis and cell-based experiments confirmed the activity and selectivity of engineered Ub-based substrates and probes. Using this approach, we propose that for any protease that recognizes Ub and Ub-like substrates, a highly active and selective unnatural substrate or probe can be engineered.",2020-01-31,"Rut, W.; Zmudzinski, M.; Snipas, S. J.; Bekes, M.; Huang, T. T.; Drag, M.",,,,False
63c117d5bd4fa8fc29b0b1240e2ea9b75712169e,biorxiv,MRCA time and epidemic dynamics of the 2019 novel coronavirus,doi.org/10.1101/2020.01.25.919688,,,See https://www.biorxiv.org/about-biorxiv,"The 2019 novel coronavirus (2019-nCoV) have emerged from Wuhan, China. Studying the epidemic dynamics is crucial for further surveillance and control of the outbreak. We employed a Bayesian framework to infer the time-calibrated phylogeny and the epidemic dynamics represented by the effective reproductive number (Re) changing over time from 33 genomic sequences available from GISAID. The time of the most recent common ancestor (MRCA) was December 17, 2019 (95% HPD: December 7, 2019 - December 23, 2019). The median estimate of Re shifted from 1.6 to 1.1 on around January 1, 2020. This study provides an early insight of the 2019-nCoV epidemic. However, due to limited amount of data, one should be cautious when interpreting the results at this stage.",2020-01-31,"Zhang, C.; Wang, M.",,,,False
ffc9bc4ac6548cb1c03c2c6f088ab1c1c2067c6f,biorxiv,Nucleotide Analogues as Inhibitors of Viral Polymerases,doi.org/10.1101/2020.01.30.927574,,,See https://www.biorxiv.org/about-biorxiv,"Coronaviruses such as the newly discovered virus from Wuhan, China, 2019-nCoV, and the viruses that cause SARS and MERS, have resulted in regional and global public health emergencies. Based on our molecular insight that the hepatitis C virus and the coronavirus use a similar viral genome replication mechanism, we reasoned that the FDA-approved drug EPCLUSA (Sofosbuvir/Velpatasvir) for the treatment of hepatitis C will also inhibit the above coronaviruses, including 2019-nCoV. To develop broad spectrum anti-viral agents, we further describe a novel strategy to design and synthesize viral polymerase inhibitors, by combining the ProTide Prodrug approach used in the development of Sofosbuvir with the use of 3-blocking groups that we have previously built into nucleotide analogues that function as polymerase terminators.",2020-01-31,"Ju, J.; Kumar, S.; Li, X.; Jockusch, S.; Russo, J. J.",,,,True
8d47a74dc0598f1039bad9e35970da53230aeff5,biorxiv,The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes,doi.org/10.1101/2020.01.30.927806,,,See https://www.biorxiv.org/about-biorxiv,"Since December 2019, a newly identified coronavirus (2019 novel coronavirus, 2019-nCov) is causing outbreak of pneumonia in one of largest cities, Wuhan, in Hubei province of China and has draw significant public health attention. The same as severe acute respiratory syndrome coronavirus (SARS-CoV), 2019-nCov enters into host cells via cell receptor angiotensin converting enzyme II (ACE2). In order to dissect the ACE2-expressing cell composition and proportion and explore a potential route of the 2019-nCov infection in digestive system infection, 4 datasets with single-cell transcriptomes of lung, esophagus, gastric, ileum and colon were analyzed. The data showed that ACE2 was not only highly expressed in the lung AT2 cells, esophagus upper and stratified epithelial cells but also in absorptive enterocytes from ileum and colon. These results indicated along with respiratory systems, digestive system is a potential routes for 2019-nCov infection. In conclusion, this study has provided the bioinformatics evidence of the potential route for infection of 2019-nCov in digestive system along with respiratory tract and may have significant impact for our healthy policy setting regards to prevention of 2019-nCoV infection.",2020-01-31,"Zhang, H.; Kang, Z.; Gong, H.; Xu, D.; Wang, J.; Li, Z.; Cui, X.; Xiao, J.; Meng, T.; Zhou, W.; Liu, J.; Xu, H.",,,,False
eae11a3f01b79e76a968bfb84886432f04584596,biorxiv,The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells,doi.org/10.1101/2020.01.31.929042,,,See https://www.biorxiv.org/about-biorxiv,"The emergence of a novel, highly pathogenic coronavirus, 2019-nCoV, in China, and its rapid national and international spread pose a global health emergency. Coronaviruses use their spike proteins to select and enter target cells and insights into nCoV-2019 spike (S)-driven entry might facilitate assessment of pandemic potential and reveal therapeutic targets. Here, we demonstrate that 2019-nCoV-S uses the SARS-coronavirus receptor, ACE2, for entry and the cellular protease TMPRSS2 for 2019-nCoV-S priming. A TMPRSS2 inhibitor blocked entry and might constitute a treatment option. Finally, we show that the serum form a convalescent SARS patient neutralized 2019-nCoV-S-driven entry. Our results reveal important commonalities between 2019-nCoV and SARS-coronavirus infection, which might translate into similar transmissibility and disease pathogenesis. Moreover, they identify a target for antiviral intervention.  One sentence summaryThe novel 2019 coronavirus and the SARS-coronavirus share central biological properties which can guide risk assessment and intervention.",2020-01-31,"Hoffmann, M.; Kleine-Weber, H.; Krueger, N.; Mueller, M. A.; Drosten, C.; Poehlmann, S.",,,,True
2ff168d83528e6dd46e8c5358fb84fd63f7a8f2c,biorxiv,"VIDHOP, viral host prediction with Deep Learning",doi.org/10.1101/575571,,,See https://www.biorxiv.org/about-biorxiv,"MotivationZoonosis, the natural transmission of infections from animals to humans, is a far-reaching global problem. The recent outbreaks of Zika virus, Ebola virus and Corona virus are examples of viral zoonosis, which occur more frequently due to globalization. In the case of a virus outbreak, it is helpful to know which host organism was the original carrier of the virus. Once the reservoir or intermediate host is known, it can be isolated to prevent further spreading of the viral infection. Recent approaches aim to predict a viral host based on the viral genome, often in combination with the potential host genome and arbitrarily selected features. These methods have a clear limitation in either the number of different hosts they can predict or the accuracy of their prediction.  ResultsHere, we present a fast and accurate deep learning approach for viral host prediction, which is based on the viral genome sequence only. To ensure a high prediction accuracy, we developed an effective selection approach for the training data to avoid biases due to a highly unbalanced number of known sequences per virus-host combinations. We tested our deep neural network on three different virus species (influenza A, rabies lyssavirus, rotavirus A). We reached for each virus species an AUG between 0.93 and 0.98, outperforming previous approaches and allowing highly accurate predictions while only using fractions (100-400 bp) of the viral genome sequences. We show that deep neural networks are suitable to predict the host of a virus, even with a limited amount of sequences and highly unbalanced available data. The deep neural networks trained for this approach build the core of the virus-host predicting tool VIDHOP (Virus Deep learning HOst Prediction).  AvailabilityThe trained models for the prediction of the host for the viruses influenza A, rabies lyssavirus, rotavirus A are implemented in the tool VIDHOP. This tool is freely available under https://github.com/flomock/vidhop.  Supplementary informationSupplementary data are available at DOI 10.17605/OSF.IO/UXT7N",2020-01-31,"Mock, F.; Viehweger, A.; Barth, E.; Marz, M.",,,,True
32c2e402c3c88c3024a4dec3d78ba67c24f89ca6,biorxiv,"Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence",doi.org/10.1101/696195,,,See https://www.biorxiv.org/about-biorxiv,"Bats host virulent zoonotic viruses without experiencing disease. A mechanistic understanding of the impact of bats virus hosting capacities, including uniquely constitutive immune pathways, on cellular-scale viral dynamics is needed to elucidate zoonotic emergence. We carried out virus infectivity assays on bat cell lines expressing induced and constitutive immune phenotypes, then developed a theoretical model of our in vitro system, which we fit to empirical data. Best fit models recapitulated expected immune phenotypes for representative cell lines, supporting robust antiviral defenses in bat cells that correlated with higher estimates for within-host viral propagation rates. In general, heightened immune responses limit pathogen-induced cellular morbidity, which can facilitate the establishment of rapidly-propagating persistent infections within-host. Rapidly-replicating viruses that have evolved with bat immune systems will likely cause enhanced virulence following emergence into secondary hosts with immune systems that diverge from those unique to bats.",2020-02-01,"Brook, C. E.; Boots, M.; Chandran, K.; Dobson, A. P.; Drosten, C.; Graham, A. L.; Grenfell, B.; Müller, M. A.; Ng, M.; Wang, L.-F.; van Leeuwen, A.",,,,True
ee986ee9617cddea4f905898fc76512afd10ae1f,biorxiv,Interpretable detection of novel human viruses from genome sequencing data,doi.org/10.1101/2020.01.29.925354,,,See https://www.biorxiv.org/about-biorxiv,"Viruses evolve extremely quickly, so reliable methods for viral host prediction are necessary to safeguard biosecurity and biosafety alike. Novel human-infecting viruses are difficult to detect with standard bioinformatics workflows. Here, we predict whether a virus can infect humans directly from next-generation sequencing reads. We show that deep neural architectures significantly outperform both shallow machine learning and standard, homology-based algorithms, cutting the error rates in half and generalizing to taxonomic units distant from those presented during training. We propose a new approach for convolutional filter visualization to disentangle the information content of each nucleotide from its contribution to the final classification decision. Nucleotide-resolution maps of the learned associations between pathogen genomes and the infectious phenotype can be used to detect virulence-related genes in novel agents, as we show here for the 2019-nCoV coronavirus, unknown before it caused a pneumonia outbreak in December 2019.",2020-02-01,"Bartoszewicz, J. M.; Seidel, A.; Renard, B. Y.",,,,True
0e1b33290ff06012a46d64a044a4a69f60fb7513,biorxiv,Rats Sniff Off Toxic Air,doi.org/10.1101/739003,,,See https://www.biorxiv.org/about-biorxiv,"Breathing air is a fundamental human need, yet its safety, when challenged by various harmful or lethal substances, is often not properly guarded. For example, air toxicity is currently monitored only for single or limited number of known toxicants, thus failing to fully warn against possible hazardous air. Here, we discovered that within minutes living rats emitted distinctive profiles of volatile organic compounds (VOCs) via breath when exposed to various airborne toxicants such as endotoxin, O3, ricin, and CO2. Compared to background indoor air, when exposed to ricin or endotoxin aerosols breath-borne VOC levels, especially that of carbon disulfide, were shown to decrease; while their elevated levels were observed for O3 and CO2 exposures. A clear contrast in breath-borne VOCs profiles of rats between different toxicant exposures was observed with a statistical significance. Differences in MicroRNA regulations such as miR-33, miR-146a and miR-155 from rats blood samples revealed different mechanisms used by the rats in combating different air toxicant challenges. Similar to dogs, rats were found here to be able to sniff against toxic air by releasing a specific breath-borne VOC profile. The discovered science opens a new arena for online monitoring air toxicity and health effects of pollutants.  TOC  O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC=""FIGDIR/small/739003v3_ufig1.gif"" ALT=""Figure 1""> View larger version (29K): org.highwire.dtl.DTLVardef@f419cdorg.highwire.dtl.DTLVardef@1ca1582org.highwire.dtl.DTLVardef@4a35ceorg.highwire.dtl.DTLVardef@128b6f_HPS_FORMAT_FIGEXP  M_FIG C_FIG",2020-02-01,"Chen, H.; Li, X.; Yao, M.",,,,False
bb97f90ff5bfd41f2f1148c5cbdb257fdba535df,biorxiv,"Complete genome characterisation of a novel coronavirus associated with severe human respiratory disease in Wuhan, China",doi.org/10.1101/2020.01.24.919183,,,See https://www.biorxiv.org/about-biorxiv,"Emerging and re-emerging infectious diseases, such as SARS, MERS, Zika and highly pathogenic influenza present a major threat to public health1-3. Despite intense research effort, how, when and where novel diseases appear are still the source of considerable uncertainly. A severe respiratory disease was recently reported in the city of Wuhan, Hubei province, China. At the time of writing, at least 62 suspected cases have been reported since the first patient was hospitalized on December 12nd 2019. Epidemiological investigation by the local Center for Disease Control and Prevention (CDC) suggested that the outbreak was associated with a sea food market in Wuhan. We studied seven patients who were workers at the market, and collected bronchoalveolar lavage fluid (BALF) from one patient who exhibited a severe respiratory syndrome including fever, dizziness and cough, and who was admitted to Wuhan Central Hospital on December 26th 2019. Next generation metagenomic RNA sequencing4 identified a novel RNA virus from the family Coronaviridae designed WH-Human-1 coronavirus (WHCV).  Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that WHCV was most closely related (89.1% nucleotide similarity similarity) to a group of Severe Acute Respiratory Syndrome (SARS)-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) previously sampled from bats in China and that have a history of genomic recombination. This outbreak highlights the ongoing capacity of viral spill-over from animals to cause severe disease in humans.",2020-02-02,"Wu, F.; Zhao, S.; Yu, B.; Chen, Y.-M.; Wang, W.; Hu, Y.; Song, Z.-G.; Tao, Z.-W.; Tian, J.-H.; Pei, Y.-Y.; Yuan, M.-L.; Zhang, Y.-L.; Dai, F.-H.; Liu, Y.; Wang, Q.-M.; Zheng, J.-J.; Xu, L.; Holmes, E. C.; Zhang, Y.-Z.",,,,True
0c27c0ddaa4761f6155838df81a88d24619720f8,biorxiv,Genome Detective Coronavirus Typing Tool for rapid identification and characterization of novel coronavirus genomes,doi.org/10.1101/2020.01.31.928796,,,See https://www.biorxiv.org/about-biorxiv,"SummaryGenome Detective is a web-based, user-friendly software application to quickly and accurately assemble all known virus genomes from next generation sequencing datasets. This application allows the identification of phylogenetic clusters and genotypes from assembled genomes in FASTA format. Since its release in 2019, we have produced a number of typing tools for emergent viruses that have caused large outbreaks, such as Zika and Yellow Fever Virus in Brazil. Here, we present The Genome Detective Coronavirus Typing Tool that can accurately identify novel coronavirus (2019-nCoV) sequences isolated in China and around the world. The tool can accept up to 2,000 sequences per submission and the analysis of a new whole genome sequence will take approximately one minute. The tool has been tested and validated with hundreds of whole genomes from ten coronavirus species, and correctly classified all of the SARS-related coronavirus (SARSr-CoV) and all of the available public data for 2019-nCoV. The tool also allows tracking of new viral mutations as the outbreak expands globally, which may help to accelerate the development of novel diagnostics, drugs and vaccines.  AvailabilityAvailable online: https://www.genomedetective.com/app/typingtool/cov  * Contactkoen@emweb.be and deoliveira@ukzn.ac.za  Supplementary informationSupplementary data is available online.",2020-02-02,"Cleemput, S.; Dumon, W.; Fonseca, V.; Abdool Karim, W.; Giovanetti, M.; Alcantara, L. C. J.; Deforche, K.; de Oliveira, T.",,,,True
b7229959c1fa6de4fc0d4cf12bb45cb9e2e93974,biorxiv,Highly Distinguished Amino Acid Sequences of 2019-nCoV (Wuhan Coronavirus),doi.org/10.1101/2020.01.31.929497,,,See https://www.biorxiv.org/about-biorxiv,"Using a method for pathogen screening in DNA synthesis orders, we have identified a number of amino acid sequences that distinguish 2019-nCoV (Wuhan Coronavirus) from all other known viruses in Coronaviridae. We find three main regions of unique sequence: two in the 1ab polyprotein QHO60603.1, one in surface glycoprotein QHO60594.1.",2020-02-02,"Beal, J.; Mitchell, T.; Wyschogrod, D.; Manthey, J.; Clore, A.",,,,False
a05179c57d5e1cdddc839ff3c0b70a614efbb6cb,biorxiv,Host and infectivity prediction of Wuhan 2019 novel coronavirus using deep learning algorithm,doi.org/10.1101/2020.01.21.914044,,,See https://www.biorxiv.org/about-biorxiv,"The recent outbreak of pneumonia in Wuhan, China caused by the 2019 Novel Coronavirus (2019-nCoV) emphasizes the importance of detecting novel viruses and predicting their risks of infecting people. In this report, we introduced the VHP (Virus Host Prediction) to predict the potential hosts of viruses using deep learning algorithm. Our prediction suggests that 2019-nCoV has close infectivity with other human coronaviruses, especially the severe acute respiratory syndrome coronavirus (SARS-CoV), Bat SARS-like Coronaviruses and the Middle East respiratory syndrome coronavirus (MERS-CoV). Based on our prediction, compared to the Coronaviruses infecting other vertebrates, bat coronaviruses are assigned with more similar infectivity patterns with 2019-nCoVs. Furthermore, by comparing the infectivity patterns of all viruses hosted on vertebrates, we found mink viruses show a closer infectivity pattern to 2019-nCov. These consequences of infectivity pattern analysis illustrate that bat and mink may be two candidate reservoirs of 2019-nCov.These results warn us to beware of 2019-nCoV and guide us to further explore the properties and reservoir of it.  One Sentence SummaryIt is of great value to identify whether a newly discovered virus has the risk of infecting human. Guo et al. proposed a virus host prediction method based on deep learning to detect what kind of host a virus can infect with DNA sequence as input. Applied to the Wuhan 2019 Novel Coronavirus, our prediction demonstrated that several vertebrate-infectious coronaviruses have strong potential to infect human. This method will be helpful in future viral analysis and early prevention and control of viral pathogens.",2020-02-02,"Guo, Q.; Li, M.; Wang, C.; Fang, Z.; Wang, P.; Tan, J.; Wu, S.; Xiao, Y.; Zhu, H.",,,,True
ff54e3e961a72eb1d2500166809b3651b2f98cf6,biorxiv,"Predicting commercially available antiviral drugs that may act on the novel coronavirus (2019-nCoV), Wuhan, China through a drug-target interaction deep learning model",doi.org/10.1101/2020.01.31.929547,,,See https://www.biorxiv.org/about-biorxiv,"The infection of a novel coronavirus found in Wuhan of China (2019-nCoV) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for 2019-nCoV, various strategies are being tested in China, including drug repurposing. In this study, we used our pretrained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of 2019-nCoV. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing a inhibitory potency with Kd of 94.94 nM against the 2019-nCoV 3C-like proteinase, followed by efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of 2019-nCoV with an inhibitory potency with Kd < 1000 nM. In addition, we also found that several antiviral agents, such as Kaletra, could be used for the treatment of 2019-nCoV, although there is no real-world evidence supporting the prediction. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for 2019-nCoV.",2020-02-02,"Beck, B. R.; Shin, B.; Choi, Y.; Park, S.; Kang, K.",,,,True
f162829ffeba4cedd16aaf7f09902182c5cf903c,biorxiv,DNA breaks-mediated cost reveals RNase HI as a new target for selectively eliminating antibiotic resistance,doi.org/10.1101/756767,,,See https://www.biorxiv.org/about-biorxiv,"Antibiotic resistance often generates a fitness cost to bacteria in drug-free environments. Understanding the causes of the cost is considered the Holy Grail in the antibiotic resistance field, as it is the main determinant of the prevalence of resistances upon reducing antibiotics use. We show that DNA breaks can explain most of the variation in the cost of resistances common in pathogens. Here we demonstrate that targeting the RNase that degrades R-loops, which cause DNA breaks, exacerbates the cost of resistance. Consequently, lack of RNase HI function drives resistant clones to extinction in populations with high initial frequency of resistance, both in laboratory conditions and in a mouse model of gut colonization. Thus, RNase HI provides a target specific against resistant bacteria, which we validate using a repurposed drug. In summary, we revealed key mechanisms underlying the cost of antibiotic resistance that can be exploited to specifically eliminate resistant bacteria.",2020-02-03,"Balbontin, R.; Frazao, N.; Gordo, I.",,,,True
a8e53c77bc72f467723a7d5b8020875c0e96f8aa,biorxiv,Potent neutralization of 2019 novel coronavirus by recombinant ACE2-Ig,doi.org/10.1101/2020.02.01.929976,,,See https://www.biorxiv.org/about-biorxiv,"2019-nCoV, which is a novel coronavirus emerged in Wuhan, China, at the end of 2019, has caused at least infected 11,844 as of Feb 1, 2020. However, there is no specific antiviral treatment or vaccine currently. Very recently report had suggested that novel CoV would use the same cell entry receptor, ACE2, as the SARS-CoV. In this report, we generated a novel recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. An ACE2 mutant with low catalytic activity was also used in the study. The fusion proteins were then characterized. Both fusion proteins has high affinity binding to the receptor-binding domain (RBD) of SARS-CoV and 2019-nCoV and exerted desired pharmacological properties. Moreover, fusion proteins potently neutralized SARS-CoV and 2019-nCoV in vitro. As these fusion proteins exhibit cross-reactivity against coronaviruses, they could have potential applications for diagnosis, prophylaxis, and treatment of 2019-nCoV.",2020-02-03,"Lei, C.; Fu, W.; Qian, K.; Li, T.; Zhang, S.; Ding, M.; Hu, S.",,,,True
836190d366ba8e34c3a5df8a24d17a36fd503505,biorxiv,Fast assessment of human receptor-binding capability of 2019 novel coronavirus (2019-nCoV),doi.org/10.1101/2020.02.01.930537,,,See https://www.biorxiv.org/about-biorxiv,"The outbreaks of 2002/2003 SARS, 2012/2015 MERS and 2019/2020 Wuhan respiratory syndrome clearly indicate that genome evolution of an animal coronavirus (CoV) may enable it to acquire human transmission ability, and thereby to cause serious threats to global public health. It is widely accepted that CoV human transmission is driven by the interactions of its spike protein (S-protein) with human receptor on host cell surface; so, quantitative evaluation of these interactions may be used to assess the human transmission capability of CoVs. However, quantitative methods directly using viral genome data are still lacking. Here, we perform large-scale protein-protein docking to quantify the interactions of 2019-nCoV S-protein receptor-binding domain (S-RBD) with human receptor ACE2, based on experimental SARS-CoV S-RBD-ACE2 complex structure. By sampling a large number of thermodynamically probable binding conformations with Monte Carlo algorithm, this approach successfully identified the experimental complex structure as the lowest-energy receptor-binding conformations, and hence established an experiment-based strength reference for evaluating the receptor-binding affinity of 2019-nCoV via comparison with SARS-CoV. Our results show that this binding affinity is about 73% of that of SARS-CoV, supporting that 2019-nCoV may cause human transmission similar to that of SARS-CoV. Thus, this study presents a method for rapidly assessing the human transmission capability of a newly emerged CoV and its mutant strains, and demonstrates that post-genome analysis of protein-protein interactions may provide early scientific guidance for viral prevention and control.",2020-02-04,"Huang, Q.; Herrmann, A.",,,,True
acb0e11e5763dbf7588ec435751a2ab705a783f1,biorxiv,Insights into Cross-species Evolution of Novel Human Coronavirus 2019-nCoV and Defining Immune Determinants for Vaccine Development,doi.org/10.1101/2020.01.29.925867,,,See https://www.biorxiv.org/about-biorxiv,"Novel Coronavirus (nCoV) outbreak in the city of Wuhan, China during December 2019, has now spread to various countries across the globe triggering a heightened containment effort. This human pathogen is a member of betacoronavirus genus carrying 30 kilobase of single positive-sense RNA genome. Understanding the evolution, zoonotic transmission, and source of this novel virus would help accelerating containment and prevention efforts. The present study reported detailed analysis of 2019-nCoV genome evolution and potential candidate peptides for vaccine development. This nCoV genotype might have been evolved from a bat-CoV by accumulating non-synonymous mutations, indels, and recombination events. Structural proteins Spike (S), and Membrane (M) had extensive mutational changes, whereas Envelope (E) and Nucleocapsid (N) proteins were very conserved suggesting differential selection pressures exerted on 2019-nCoV during evolution. Interestingly, 2019-nCoV Spike protein contains a 39 nucleotide sequence insertion relative to SARS-like bat-SL-CoVZC45/2017. Furthermore, we identified eight high binding affinity (HBA) CD4 T-cell epitopes in the S, E, M and N proteins, which can be commonly recognized by HLA-DR alleles of Asia and Asia-Pacific Region population. These immunodominant epitopes can be incorporated in universal subunit CoV vaccine. Diverse HLA types and variations in the epitope binding affinity may contribute to the wide range of immunopathological outcomes of circulating virus in humans. Our findings emphasize the requirement for continuous surveillance of CoV strains in live animal markets to better understand the viral adaptation to human host and to develop practical solutions to prevent the emergence of novel pathogenic CoV strains.",2020-02-04,"Ramaiah, A.; Arumugaswami, V.",,,,True
6ae20454d1a9f228864de24660c2460becbc8151,biorxiv,Machine intelligence design of 2019-nCoV drugs,doi.org/10.1101/2020.01.30.927889,,,See https://www.biorxiv.org/about-biorxiv,"Wuhan coronavirus, called 2019-nCoV, is a newly emerged virus that infected more than 9692 people and leads to more than 213 fatalities by January 30, 2020. Currently, there is no effective treatment for this epidemic. However, the viral protease of a coronavirus is well-known to be essential for its replication and thus is an effective drug target. Fortunately, the sequence identity of the 2019-nCoV protease and that of severe-acute respiratory syndrome virus (SARS-CoV) is as high as 96.1%. We show that the protease inhibitor binding sites of 2019-nCoV and SARS-CoV are almost identical, which means all potential anti-SARS-CoV chemotherapies are also potential 2019-nCoV drugs. Here, we report a family of potential 2019-nCoV drugs generated by a machine intelligence-based generative network complex (GNC). The potential effectiveness of treating 2019-nCoV by using some existing HIV drugs is also analyzed.",2020-02-04,"Nguyen, D. D.; Gao, K.; Wang, R.; Wei, G.",,,,True
6c91b00faa16142426820016ad3a7847fc77c8e4,biorxiv,Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection,doi.org/10.1101/2020.02.03.931766,,,See https://www.biorxiv.org/about-biorxiv,"A newly identified coronavirus, 2019-nCoV, has been posing significant threats to public health since December 2019. ACE2, the host cell receptor for severe acute respiratory syndrome coronavirus (SARS), has recently been demonstrated in mediating 2019-nCoV infection. Interestingly, besides the respiratory system, substantial proportion of SARS and 2019-nCoV patients showed signs of various degrees of liver damage, the mechanism and implication of which have not yet been determined. Here, we performed an unbiased evaluation of cell type specific expression of ACE2 in healthy liver tissues using single cell RNA-seq data of two independent cohorts, and identified specific expression in cholangiocytes. The results indicated that virus might directly bind to ACE2 positive cholangiocytes but not necessarily hepatocytes. This finding suggested the liver abnormalities of SARS and 2019-nCoV patients may not be due to hepatocyte damage, but cholangiocyte dysfunction and other causes such as drug induced and systemic inflammatory response induced liver injury. Our findings indicate that special care of liver dysfunction should be installed in treating 2019-nCoV patients during the hospitalization and shortly after cure.",2020-02-04,"Chai, X.; Hu, L.; Zhang, Y.; Han, W.; Lu, Z.; Ke, A.; Zhou, J.; Shi, G.; Fang, N.; Fan, J.; Cai, J.; Fan, J.; Lan, F.",,,,True
3c12e50b9da4b1fde21d68040610b73b8c216bf3,biorxiv,Structure-Guided Mutagenesis Alters Deubiquitinating Activity 2 and Attenuates Pathogenesis of a Murine Coronavirus,doi.org/10.1101/782409,,,See https://www.biorxiv.org/about-biorxiv,"Coronaviruses express a multifunctional papain-like protease, termed PLP2. PLP2 acts as a protease that cleaves the viral replicase polyprotein, and a deubiquitinating (DUB) enzyme which removes ubiquitin moieties from ubiquitin-conjugated proteins. Previous in vitro studies implicated PLP2 DUB activity as a negative regulator of the host interferon (IFN) response, but the role of DUB activity during virus infection was unknown. Here, we used X-ray structure-guided mutagenesis and functional studies to identify amino acid substitutions within the ubiquitin-binding surface of PLP2 that reduced DUB activity without affecting polyprotein processing activity. We engineered a DUB mutation (Asp1772 to Ala) into a murine coronavirus and evaluated the replication and pathogenesis of the DUB mutant virus (DUBmut) in cultured macrophages and in mice. We found that the DUBmut virus replicates similarly as the wild-type virus in cultured cells, but the DUBmut virus activates an IFN response at earlier times compared to the wild-type virus infection in macrophages, consistent with DUB activity negatively regulating the IFN response. We compared the pathogenesis of the DUBmut virus to the wild-type virus and found that the DUBmut-infected mice had a statistically significant reduction (p<0.05) in viral titer in livers and spleens at day 5 post-infection, albeit both wild-type and DUBmut virus infections resulted in similar liver pathology. Overall, this study demonstrates that structure-guided mutagenesis aids the identification of critical determinants of PLP2-ubiquitin complex, and that PLP2 DUB activity plays a role as an interferon antagonist in coronavirus pathogenesis.  ImportanceCoronaviruses employ a genetic economy by encoding multifunctional proteins that function in viral replication and also modify the host environment to disarm the innate immune response. The coronavirus papain-like protease 2 (PLP2) domain possesses protease activity, which cleaves the viral replicase polyprotein, and also DUB activity (de-conjugating ubiquitin/ubiquitin-like molecules from modified substrates) using identical catalytic residues. To separate the DUB activity from the protease activity, we employed a structure-guided mutagenesis approach and identified residues that are important for ubiquitin-binding. We found that mutating the ubiquitin-binding residues results in a PLP2 that has reduced DUB activity but retains protease activity. We engineered a recombinant murine coronavirus to express the DUB mutant and showed that the DUB mutant virus activated an earlier type I interferon response in macrophages and exhibited reduced pathogenesis in mice. The results of this study demonstrate that PLP2/DUB is an interferon antagonist and a virulence trait of coronaviruses.",2020-02-04,"Deng, X.; Chen, Y.; Mielech, A. M.; Hackbart, M.; Kesely, K. R.; Mettelman, R. C.; OBrien, A.; Chapman, M. E.; Mesecar, A. D.; Baker, S. C.",,,,True
4d6f0f3ca20fad69e80ff76b89fdafe39d7ed7d5,biorxiv,Genomic variance of the 2019-nCoV coronavirus,doi.org/10.1101/2020.02.02.931162,,,See https://www.biorxiv.org/about-biorxiv,"There is rising global concern for the recently emerged novel Coronavirus (2019-nCov). Full genomic sequences have been released by the worldwide scientific community in the last few weeks in order to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and SARS. We confirm high sequence similarity (>99%) between all sequenced 2019-nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019-nCoV. Despite the low heterogeneity of the 2019-nCoV genomes, we could identify at least two hyper-variable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8-encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti-coronavirus approaches.",2020-02-05,"Ceraolo, C.; Giorgi, F. M.",,,,False
07523054c7442457ed75062c030ce437bd28b932,biorxiv,A database resource for Genome-wide dynamics analysis of Coronaviruses on a historical and global scale,doi.org/10.1101/2020.02.05.920009,,,See https://www.biorxiv.org/about-biorxiv,"The recent outbreak of a new zoonotic origin Coronavirus has ring the bell for the potential spread of epidemic Coronavirus crossing the species. With the urgent needs to assist the control of the Coronavirus spread and to provide valuable scientific information, we developed a coronavirus database (CoVdb), an online genomics and proteomics analysis platform. Based on public available coronavirus genomic information, the database annotates the genome of every strain and identifies 780 possible ORFs of all strains available in Genebank. In addition, the comprehensive evaluation of all the published genomes of Coronavirus strains, including population genetics analysis, functional analysis and structural analysis on a historical and global scale were presented in the CoVdb. In the database, the researcher can easily obtain the basic information of a Coronavirus gene with the distribution of the gene among strains, conserved or high mutation regions, possible subcellular location and topology of the gene. Moreover, sliding windows for population genetics analysis results is provided, thereby facilitating genetics and evolutional analysis at the genomic level. CoVdb can be accessed freely at http://covdb.popgenetics.net.",2020-02-07,"Zhu, Z.; Meng, K.; Meng, G.",,,,False
8a1fde8c65e439496ac5810504de23ef77312f28,biorxiv,Protein structure and sequence re-analysis of 2019-nCoV genome does not indicate snakes as its intermediate host or the unique similarity between its spike protein insertions and HIV-1,doi.org/10.1101/2020.02.04.933135,,,See https://www.biorxiv.org/about-biorxiv,"As the infection of 2019-nCoV coronavirus is quickly developing into a global pneumonia epidemic, careful analysis of its transmission and cellular mechanisms is sorely needed. In this report, we re-analyzed the computational approaches and findings presented in two recent manuscripts by Ji et al. (https://doi.org/10.1002/jmv.25682) and by Pradhan et al. (https://doi.org/10.1101/2020.01.30.927871), which concluded that snakes are the intermediate hosts of 2019-nCoV and that the 2019-nCoV spike protein insertions shared a unique similarity to HIV-1. Results from our re-implementation of the analyses, built on larger-scale datasets using state-of-the-art bioinformatics methods and databases, do not support the conclusions proposed by these manuscripts. Based on our analyses and existing data of coronaviruses, we concluded that the intermediate hosts of 2019-nCoV are more likely to be mammals and birds than snakes, and that the ""novel insertions"" observed in the spike protein are naturally evolved from bat coronaviruses.",2020-02-08,"Zhang, C.; Zheng, W.; Huang, X.; Bell, E. W.; Zhou, X.; Zhang, Y.",,,,True
83323659de2f2d5ed3ca6ada7cf137a8a17bb014,biorxiv,Alpha-ketoamides as broad-spectrum inhibitors of coronavirus and enterovirus replication,doi.org/10.1101/2020.02.10.936898,,,See https://www.biorxiv.org/about-biorxiv,"The main protease of coronaviruses and the 3C protease of enteroviruses share a similar active-site architecture and a unique requirement for glutamine in the P1 position of the substrate. Because of their unique specificity and essential role in viral polyprotein processing, these proteases are suitable targets for the development of antiviral drugs. In order to obtain near-equipotent, broad-spectrum antivirals against alphacoronaviruses, betacoronaviruses, and enteroviruses, we pursued structure-based design of peptidomimetic -ketoamides as inhibitors of main and 3C proteases. Six crystal structures of protease:inhibitor complexes were determined as part of this study. Compounds synthesized were tested against the recombinant proteases as well as in viral replicons and virus-infected cell cultures; most of them were not cell-toxic. Optimization of the P2 substituent of the -ketoamides proved crucial for achieving near-equipotency against the three virus genera. The best near-equipotent inhibitors, 11u (P2 = cyclopentylmethyl) and 11r (P2 = cyclohexylmethyl), display low-micromolar EC50 values against enteroviruses, alphacoronaviruses, and betacoronaviruses in cell cultures. In Huh7 cells, 11r exhibits three-digit picomolar activity against Middle East Respiratory Syndrome coronavirus.",2020-02-10,"Zhang, L.; Lin, D.; Kusov, Y.; Nian, Y.; Ma, Q.; Wang, J.; von Brunn, A.; Leyssen, P.; Lanko, K.; Neyts, J.; de Wilde, A.; Snijder, E. J.; Liu, H.; Hilgenfeld, R.",,,,True
35ac99bfeb665ce0a2ae361dba1161e69eb8b7d5,biorxiv,{Phi}X174 Attenuation by Whole Genome Codon Deoptimization,doi.org/10.1101/2020.02.10.942847,,,See https://www.biorxiv.org/about-biorxiv,"Natural selection acting on synonymous mutations in protein-coding genes influences genome composition and evolution. In viruses, introducing synonymous mutations in genes encoding structural proteins can drastically reduce viral growth, providing a means to generate potent, live attenuated vaccine candidates. However, an improved understanding of what compositional features are under selection and how combinations of synonymous mutations affect viral growth is needed to predictably attenuate viruses and make them resistant to reversion. We systematically recoded all non-overlapping genes of the bacteriophage {Phi}X174 with codons rarely used in its E. coli host. The fitness of recombinant viruses decreases as additional deoptimizing mutations are made to the genome, although not always linearly, and not consistently across genes. Combining deoptimizing mutations may reduce viral fitness more or less than expected from the effect size of the constituent mutations and we point out difficulties in untangling correlated compositional features. We test our model by optimizing the same genes and find that the relationship between codon usage and fitness does not hold for optimization, suggesting that wild-type {Phi}X174 is at a fitness optimum. This work highlights the need to better understand how selection acts on patterns of synonymous codon usage across the genome and provides a convenient system to investigate the genetic determinants of virulence.",2020-02-11,"Van Leuven, J. T.; Ederer, M. M.; Burleigh, K.; Scott, L.; Hughes, R. A.; Codrea, V.; Ellington, A. D.; Wichman, H. A.; Miller, C. R.",,,,True
4a976fa834f9ae4744cd2887a0a195dc34b61164,biorxiv,Exploring the coronavirus epidemic using the new WashU Virus Genome Browser,doi.org/10.1101/2020.02.07.939124,,,See https://www.biorxiv.org/about-biorxiv,"Since its debut in mid-December, 2019, the novel coronavirus (2019-nCoV) has rapidly spread from its origin in Wuhan, China, to several countries across the globe, leading to a global health crisis. As of February 7, 2020, 44 strains of the virus have been sequenced and uploaded to NCBIs GenBank [1], providing insight into the viruss evolutionary history and pathogenesis. Here, we present the WashU Virus Genome Browser, a web-based portal for viewing virus genomic data. The browser is home to 16 complete 2019-nCoV genome sequences, together with hundreds of related viral sequences including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Ebola virus. In addition, the browser features unique customizability, supporting user-provided upload of novel viral sequences in various formats. Sequences can be viewed in both a track-based representation as well as a phylogenetic tree-based view, allowing the user to easily compare sequence features across multiple strains. The WashU Virus Genome Browser inherited many features and track types from the WashU Epigenome Browser, and additionally incorporated a new type of SNV track to address the specific needs of viral research. Our Virus Browser portal can be accessed at https://virusgateway.wustl.edu, and documentation is available at https://virusgateway.readthedocs.io/.",2020-02-11,"Flynn, J.; Purushotham, D.; Choudhary, M. N.; Zhuo, X.; Fan, C.; Matt, G.; Li, D.; Wang, T.",,,,False
4c24ee4a86de1d5207d93ce39132f7b660cf82e0,biorxiv,Freshwater monitoring by nanopore sequencing,doi.org/10.1101/2020.02.06.936302,,,See https://www.biorxiv.org/about-biorxiv,"Clean freshwater lies at the heart of human society and monitoring its quality is paramount. In addition to chemical controls, traditional microbiological water tests focus on the detection of specific bacterial pathogens. The direct tracing of all aquatic DNA poses a more profound alternative. Yet, this has hitherto been underused due to challenges in cost and logistics. Here we present a simple, fast, inexpensive and comprehensive freshwater diagnostics workflow centred around portable nanopore DNA sequencing. Using defined bacterial compositions and spatiotemporal microbiota from surface water of an example river in Cambridge (UK), our study shows how nanopore sequencing can be readily integrated for the assessment of aquatic bacterial diversity and pollution. We provide a computational benchmark that features more than ten taxonomic classification tools to derive guidelines for bacterial DNA analyses with nanopore data. Through complementary physicochemical measurements, we find that nanopore metagenomics can depict fine temporal gradients along the main hydrological axis of an urban-rural interface and yield high-resolution pathogen maps that address concerns of public health.",2020-02-11,"Urban, L.; Holzer, A.; Baronas, J. J.; Hall, M.; Braeuninger-Weimer, P.; Scherm, M. J.; Kunz, D. J.; Perera, S. N.; Martin-Herranz, D. E.; Tipper, E. T.; Salter, S. J.; Stammnitz, M. R.",,,,True
3e5633a9a76a8c03e4ec57e4659872a63f045117,biorxiv,"Severe acute respiratory syndrome-related coronavirus - The species and its viruses, a statement of the Coronavirus Study Group",doi.org/10.1101/2020.02.07.937862,,,See https://www.biorxiv.org/about-biorxiv,"The present outbreak of lower respiratory tract infections, including respiratory distress syndrome, is the third spillover, in only two decades, of an animal coronavirus to humans resulting in a major epidemic. Here, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the official classification of viruses and taxa naming (taxonomy) of the Coronaviridae family, assessed the novelty of the human pathogen tentatively named 2019-nCoV. Based on phylogeny, taxonomy and established practice, the CSG formally recognizes this virus as a sister to severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus and designates it as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To facilitate communication, the CSG further proposes to use the following naming convention for individual isolates: SARS-CoV-2/Isolate/Host/Date/Location. The spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined. The independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying the entire (virus) species to complement research focused on individual pathogenic viruses of immediate significance. This research will improve our understanding of virus-host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.",2020-02-11,"Gorbalenya, A. E.",,,,True
4d1090e239baa1ea54af521f4b8bd8b5ab51fd35,biorxiv,A Generalized Discrete Dynamic Model for Human Epidemics,doi.org/10.1101/2020.02.11.944728,,,See https://www.biorxiv.org/about-biorxiv,"A discrete dynamic model for human epidemics was developed in present study. The model included major parameters as transmission strength and its decline parameters, mean incubation period, hospitalization time, non-hospitalization daily mortality, non-hospitalization daily recovery rate, and hospitalization proportion, etc. Sensitivity analysis of the model indicated the total cumulative cases significantly increased with initial transmission strength, hospitalization time. The total cumulative cases significantly decreased with transmission strengths decline and hospitalization proportion, and linearly decreased with non-hospitalization daily mortality and non-hospitalization daily recovery rate. In a certain range, the total cumulative cases significantly increased with mean incubation period. Sensitivity analysis demonstrated that dynamic change of transmission strength is one of the most important and controllable factors. In addition, reducing the delay for hospitalization is much effective in weakening disease epidemic. Non-hospitalization recovery rate is of importance for enhancing immunity to recover from the disease.",2020-02-12,"Zhang, W.; Chen, Z.; Lu, Y.; Guo, Z.; Qi, Y.; Wang, G.; Lu, J.",,,,True
181b7b57851e6f58a601b68e613d10c10616f774,biorxiv,Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies,doi.org/10.1101/2020.02.03.933226,,,See https://www.biorxiv.org/about-biorxiv,"The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the available SARS-CoV-2 sequences (as of 9 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.",2020-02-12,"Ahmed, S. F.; Quadeer, A. A.; McKay, M. R.",,,,True
a2ab0a998912ed2ec93187333dca03aa22e39a71,biorxiv,Profiling the immune vulnerability landscape of the 2019 Novel Coronavirus,doi.org/10.1101/2020.02.08.939553,,,See https://www.biorxiv.org/about-biorxiv,"The outbreak of the 2019 Novel Coronavirus (2019-nCoV) has rapidly spread from Wuhan, China to multiple countries, causing staggering number of infections and deaths. A systematic profiling of the immune vulnerability landscape of 2019-nCoV is lacking, which can bring critical insights into the immune clearance mechanism, peptide vaccine development, and antiviral antibody development. In this study, we predicted the potential of all the 2019-nCoV viral proteins to induce class I and II MHC presentation and form linear antibody epitopes. We showed that the enrichment for T cell and B cell epitopes is not uniform on the viral genome, with several focused regions that generate abundant epitopes and may be more targetable. We showed that genetic variations in 2019-nCoV, though fewer for the moment, already follow the pattern of mutations in related coronaviruses, and could alter the immune vulnerability landscape of this virus, which should be considered in the development of therapies. We create an online database to broadly share our research outcome. Overall, we present an immunological resource for 2019-nCoV that could significantly promote both therapeutic development and mechanistic research.",2020-02-12,"Zhu, J.; Kim, J.; Xiao, X.; Wang, Y.; Luo, D.; Chen, R.; Xu, L.; Zhang, H.; Xiao, G.; Zhan, X.; Wang, T.; Xie, Y.",,,,True
7e80848c7b22e870b0e0a458dce96f6955576f04,biorxiv,The network structure and eco-evolutionary dynamics of CRISPR-induced immune diversification,doi.org/10.1101/850800,,,See https://www.biorxiv.org/about-biorxiv,"As a heritable sequence-specific adaptive immune system, CRISPR-Cas is a powerful force shaping strain diversity in host-virus systems. While the diversity of CRISPR alleles has been explored, the associated structure and dynamics of host-virus interactions has not. We develop theory on the role of CRISPR immunity in mediating the interplay between host-virus interaction structure and eco-evolutionary dynamics in a computational model and three natural systems. We show that the structures of networks describing who infects whom and who is protected from whom are modular and weighted-nested, respectively. The dynamic interplay between these networks influences transitions between dynamical regimes of virus diversification and host control, leading to eventual virus extinction. The three empirical systems exhibit weighted nestedness, a pattern our theory shows is indicative of viral control by hosts. Previously missing from studies of microbial host-pathogen systems, the protection network plays a key role in the coevolutionary dynamics.",2020-02-12,"Pilosof, S.; Alcala-Corona, S. A.; Wang, T.; Kim, T.; Maslov, S.; Whitaker, R. J.; Pascual, M.",,,,True
4b56993a4d0f091e70ef5dec2e5a61c3043f752e,biorxiv,DeepTracer: Predicting Backbone Atomic Structure from High Resolution Cryo-EM Density Maps of Protein Complexes,doi.org/10.1101/2020.02.12.946772,,,See https://www.biorxiv.org/about-biorxiv,"MotivationAccurately determining the atomic structure of proteins represents a fundamental problem in the field of structural bioinformatics. A solution would be significant as protein structure information could be utilized in the medical field, e.g. in the development of vaccines for new viruses. This paper focuses on predicting the protein structure based on 3D images of the proteins captured through cryogenic electron microscopes (cryo-EM). A fully automated computationally efficient protein structure prediction method would be particularly beneficial in the field of cryo-EM as the technology allows researchers to photograph multiple large protein complexes in a single study, which means that a fast prediction method could allow for a high throughput of derived protein structures. We present a deep learning approach, DeepTracer, for predicting locations of the backbone atoms, secondary structure elements, and the amino acid types. In order to connect the predicted amino acids into chains, we applied a modified traveling salesman algorithm.  ResultsWe trained our deep learning model on experimental cryo-EM density maps and tested it on a set of 50 density maps. We found that our new approach predicted protein structures with an average RMSD value of 1.18 and a coverage of 87.5%. Furthermore, we detected secondary structure information for 87.2% of amino acids correctly. We also showed preliminarily that 25.2% of amino acid types could be predicted directly from the 3D cryo-EM density map, considering 20 different types in total. Finally, we noted that the prediction runtime of DeepTracer is significantly improved compared to other methods. It predicts a large protein complex structure of more than 30,000 amino acids in only 2 hours.  AvailabilityThe repository of this project will be published.  Contactdongsi@uw.edu  Supplementary informationSupplementary data will be available at Bioinformatics online.",2020-02-13,"Pfab, J.; Si, D.",,,,True
329dfdd2fbe4b3c510c5329219bfd33764ab1710,biorxiv,Domestication reprogrammed the budding yeast life cycle,doi.org/10.1101/2020.02.08.939314,,,See https://www.biorxiv.org/about-biorxiv,"Domestication of plants and animals is the foundation for feeding the world population. We report that domestication of the model yeast S. cerevisiae reprogrammed its life cycle entirely. We tracked growth, gamete formation and cell survival across many environments for nearly 1000 genome sequenced isolates and found a remarkable dichotomy between domesticated and wild yeasts. Wild yeasts near uniformly trigger meiosis and sporulate when encountering nutrient depletions, whereas domestication relaxed selection on sexual reproduction and favoured survival as quiescent cells. Domestication also systematically enhanced fermentative over respiratory traits while decreasing stress tolerance. We show that this yeast domestication syndrome was driven by aneuploidies and gene function losses that emerged independently in multiple domesticated lineages during the species recent evolutionary history. We found domestication to be the most dramatic event in budding yeast evolution, raising questions on how much domestication has distorted our understanding of this key model species.",2020-02-13,"De Chiara, M.; Barre, B. P.; Persson, K.; Onyetuga Chioma, A.; Irizar, A.; Schacherer, J.; Warringer, J.; Liti, G.",,,,True
adb09e4e5c7331b2aa661b3d3bb0a643e00d11bc,biorxiv,Evidence of recombination in coronaviruses implicating pangolin origins of nCoV-2019,doi.org/10.1101/2020.02.07.939207,,,See https://www.biorxiv.org/about-biorxiv,"A novel coronavirus (nCoV-2019) was the cause of an outbreak of respiratory illness detected in Wuhan, Hubei Province, China in December of 2019. Genomic analyses of nCoV-2019 determined a 96% resemblance with a coronavirus isolated from a bat in 2013 (RaTG13); however, the receptor binding motif (RBM) of these two genomes share low sequence similarity. This divergence suggests a possible alternative source for the RBM coding sequence in nCoV-2019. We identified high sequence similarity in the RBM between nCoV-2019 and a coronavirus genome reconstructed from a viral metagenomic dataset from pangolins possibly indicating a more complex origin for nCoV-2019.",2020-02-13,"Wong, M. C.; Javornik Cregeen, S. J.; Ajami, N. J.; Petrosino, J. F.",,,,True
0aff00101d5ccc6592987185ab833f95d842f98b,biorxiv,Potentially highly potent drugs for 2019-nCoV,doi.org/10.1101/2020.02.05.936013,,,See https://www.biorxiv.org/about-biorxiv,"The World Health Organization (WHO) has declared the 2019 novel coronavirus (2019-nCoV) infection outbreak a global health emergency. Currently, there is no effective anti-2019-nCoV medication. The sequence identity of the 3CL proteases of 2019-nCoV and SARS is 96%, which provides a sound foundation for structural-based drug repositioning (SBDR). Based on a SARS 3CL protease X-ray crystal structure, we construct a 3D homology structure of 2019-nCoV 3CL protease. Based on this structure and existing experimental datasets for SARS 3CL protease inhibitors, we develop an SBDR model based on machine learning and mathematics to screen 1465 drugs in the DrugBank that have been approved by the U.S. Food and Drug Administration (FDA). We found that many FDA approved drugs are potentially highly potent to 2019-nCoV.",2020-02-13,"Nguyen, D.; Gao, K.; Chen, J.; Wang, R.; Wei, G.",,,,True
dca8ced82157924ed86c698a7dd482be81b4b266,biorxiv,Teicoplanin potently blocks the cell entry of 2019-nCoV,doi.org/10.1101/2020.02.05.935387,,,See https://www.biorxiv.org/about-biorxiv,"Since December 2019, the outbreak of a new coronavirus, named 2019-nCoV, has greatly threatened the public health in China and raised great concerns worldwide. No specific treatment for this infection is currently available. We previously reported that teicoplanin, a glycopeptide antibiotic which has routinely been used in the clinic to treat bacterial infection with low toxicity, significantly inhibits the invasion of cells by Ebola virus, SARS-CoV and MERS-CoV, via specifically inhibiting the activity of cathepsin L. Here, we tested the efficacy of teicoplanin against 2019-nCoV virus infection and found that teicoplanin potently prevents the entrance of 2019-nCoV-Spike-pseudoviruses into the cytoplasm, with an IC50 of 1.66 M. Although the inhibitory effect upon the replication of wildtype viruses ex vivo and in vivo remains to be determined, our preliminary result indicates that the potential antiviral activity of teicoplanin could be applied for the treatment of 2019-nCoV virus infection.",2020-02-13,"Zhang, J.; Ma, X.; Yu, F.; Liu, J.; Zou, F.; Pan, T.; Zhang, H.",,,,True
abcfffafab399149d4adadd6bb458c4994e2025d,biorxiv,Time-varying transmission dynamics of Novel Coronavirus Pneumonia in China,doi.org/10.1101/2020.01.25.919787,,,See https://www.biorxiv.org/about-biorxiv,"RationaleSeveral studies have estimated basic production number of novel coronavirus pneumonia (NCP). However, the time-varying transmission dynamics of NCP during the outbreak remain unclear.  ObjectivesWe aimed to estimate the basic and time-varying transmission dynamics of NCP across China, and compared them with SARS.  MethodsData on NCP cases by February 7, 2020 were collected from epidemiological investigations or official websites. Data on severe acute respiratory syndrome (SARS) cases in Guangdong Province, Beijing and Hong Kong during 2002-2003 were also obtained. We estimated the doubling time, basic reproduction number (R0) and time-varying reproduction number (Rt) of NCP and SARS.  Measurements and main resultsAs of February 7, 2020, 34,598 NCP cases were identified in China, and daily confirmed cases decreased after February 4. The doubling time of NCP nationwide was 2.4 days which was shorter than that of SARS in Guangdong (14.3 days), Hong Kong (5.7 days) and Beijing (12.4 days). The R0 of NCP cases nationwide and in Wuhan were 4.5 and 4.4 respectively, which were higher than R0 of SARS in Guangdong (R0=2.3), Hongkong (R0=2.3), and Beijing (R0=2.6). The Rt for NCP continuously decreased especially after January 16 nationwide and in Wuhan. The R0 for secondary NCP cases in Guangdong was 0.6, and the Rt values were less than 1 during the epidemic.  ConclusionsNCP may have a higher transmissibility than SARS, and the efforts of containing the outbreak are effective. However, the efforts are needed to persist in for reducing time-varying reproduction number below one.  At a Glance CommentaryO_ST_ABSScientific Knowledge on the SubjectC_ST_ABSSince December 29, 2019, pneumonia infection with 2019-nCoV, now named as Novel Coronavirus Pneumonia (NCP), occurred in Wuhan, Hubei Province, China. The disease has rapidly spread from Wuhan to other areas. As a novel virus, the time-varying transmission dynamics of NCP remain unclear, and it is also important to compare it with SARS.  What This Study Adds to the FieldWe compared the transmission dynamics of NCP with SARS, and found that NCP has a higher transmissibility than SARS. Time-varying production number indicates that rigorous control measures taken by governments are effective across China, and persistent efforts are needed to be taken for reducing instantaneous reproduction number below one.",2020-02-13,"Liu, T.; Hu, J.; Xiao, J.; He, G.; Kang, M.; Rong, Z.; Lin, L.; Zhong, H.; Huang, Q.; Deng, A.; Zeng, W.; Tan, X.; Zeng, S.; Zhu, Z.; Li, J.; Gong, D.; Wan, D.; Chen, S.; Guo, L.; Li, Y.; Sun, L.; Liang, W.; Song, T.; He, J.; Ma, W.",,,,True
a22ceac8d5e1cfaf2e79557d3c794458d0e1cdbe,biorxiv,Identification of a pangolin niche for a 2019-nCoV-like coronavirus through an extensive meta-metagenomic search,doi.org/10.1101/2020.02.08.939660,,,See https://www.biorxiv.org/about-biorxiv,"In numerous instances, tracking the biological significance of a nucleic acid sequence can be augmented through the identification of environmental niches in which the sequence of interest is present. Many metagenomic datasets are now available, with deep sequencing of samples from diverse biological niches. While any individual metagenomic dataset can be readily queried using web-based tools, meta-searches through all such datasets are less accessible. In this brief communication, we demonstrate such a meta-meta-genomic approach, examining close matches to the Wuhan coronavirus 2019-nCoV in all high-throughput sequencing datasets in the NCBI Sequence Read Archive accessible with the keyword ""virome"". In addition to the homology to bat coronaviruses observed in descriptions of the 2019-nCoV sequence (F. Wu et al. 2020, Nature, doi.org/10.1038/s41586-020-2008-3; P. Zhou et al. 2020, Nature, doi.org/10.1038/s41586-020-2012-7), we note a strong homology to numerous sequence reads in a metavirome dataset generated from the lungs of deceased Pangolins reported by Liu et al. (Viruses 11:11, 2019, http://doi.org/10.3390/v11110979). Our observations are relevant to discussions of the derivation of 2019-nCoV and illustrate the utility and limitations of meta-metagenomic search tools in effective and rapid characterization of potentially significant nucleic acid sequences.  ImportanceMeta-metagenomic searches allow for high-speed, low-cost identification of potentially significant biological niches for sequences of interest.",2020-02-14,"Wahba, L.; Jain, N.; Fire, A. Z.; Shoura, M. J.; Artiles, K. L.; McCoy, M. J.; Jeong, D. E.",,,,True
7f8c673d136b9bc0aeda55e49cc72aacaa5688de,biorxiv,"Structural genomics and interactomics of 2019 Wuhan novel coronavirus, 2019-nCoV, indicate evolutionary conserved functional regions of viral proteins",doi.org/10.1101/2020.02.10.942136,,,See https://www.biorxiv.org/about-biorxiv,"During its first month, the recently emerged 2019 Wuhan novel coronavirus (2019-nCoV) has already infected many thousands of people in mainland China and worldwide and took hundreds of lives. However, the swiftly spreading virus also caused an unprecedentedly rapid response from the research community facing the unknown health challenge of potentially enormous proportions. Unfortunately, the experimental research to understand the molecular mechanisms behind the viral infection and to design a vaccine or antivirals is costly and takes months to develop. To expedite the advancement of our knowledge we leverage the data about the related coronaviruses that is readily available in public databases, and integrate these data into a single computational pipeline. As a result, we provide a comprehensive structural genomics and interactomics road-maps of 2019-nCoV and use these information to infer the possible functional differences and similarities with the related SARS coronavirus. All data are made publicly available to the research community at http://korkinlab.org/wuhan",2020-02-14,"Cui, H.; Gao, Z.; Liu, M.; Lu, S.; Mkandawire, W.; Mo, S.; Narykov, O.; Srinivasan, S.; Korkin, D.",,,,True
fc15f433048e4d9464964930c36a1e7057ba1088,biorxiv,Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation,doi.org/10.1101/2020.02.11.944462,,,See https://www.biorxiv.org/about-biorxiv,"The outbreak of a novel betacoronavirus (2019-nCov) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for urgently needed vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure (MCM) development we determined a 3.5 [A]-resolution cryo-EM structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also show biophysical and structural evidence that the 2019-nCoV S binds ACE2 with higher affinity than SARS-CoV S. Additionally we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to nCoV-2019 S, suggesting antibody cross-reactivity may be limited between the two virus RBDs. The atomic-resolution structure of 2019-nCoV S should enable rapid development and evaluation of MCMs to address the ongoing public health crisis.",2020-02-15,"Wrapp, D.; Wang, N.; Corbett, K. S.; Goldsmith, J. A.; Hsieh, C.-L.; Abiona, O.; Graham, B. S.; McLellan, J. S.",,,,True
a8e454743b0dd79bb15d6c5e8596b05e4b3e6cf0,biorxiv,The insert sequence in SARS-CoV-2 enhances spike protein cleavage by TMPRSS,doi.org/10.1101/2020.02.08.926006,,,See https://www.biorxiv.org/about-biorxiv,"At the end of 2019, the SARS-CoV-2 induces an ongoing outbreak of pneumonia in China1, even more spread than SARS-CoV infection2. The entry of SARS-CoV into host cells mainly depends on the cell receptor (ACE2) recognition and spike protein cleavage-induced cell membrane fusion3,4. The spike protein of SARS-CoV-2 also binds to ACE2 with a similar affinity, whereas its spike protein cleavage remains unclear5,6. Here we show that an insertion sequence in the spike protein of SARS-CoV-2 enhances the cleavage efficiency, and besides pulmonary alveoli, intestinal and esophagus epithelium were also the target tissues of SARS-CoV-2. Compared with SARS-CoV, we found a SPRR insertion in the S1/S2 protease cleavage sites of SARS-CoV-2 spike protein increasing the cleavage efficiency by the protein sequence aligment and furin score calculation. Additionally, the insertion sequence facilitates the formation of an extended loop which was more suitable for protease recognition by the homology modeling and molicular docking. Furthermore, the single-cell transcriptomes identified that ACE2 and TMPRSSs are highly coexpressed in AT2 cells of lung, along with esophageal upper epithelial cells and absorptive enterocytes. Our results provide the bioinformatics evidence for the increased spike protein cleavage of SARS-CoV-2 and indicate its potential target cells.",2020-02-16,"Meng, T.; Cao, H.; Zhang, H.; Kang, Z.; Xu, D.; Gong, H.; Wang, J.; Li, Z.; Cui, X.; Xu, H.; Wei, H.; Pan, X.; Zhu, R.; Xiao, J.; Zhou, W.; Cheng, L.; Liu, J.",,,,False
56a81431a148344381a1da80c877885f3f3d6d59,biorxiv,Direct nanopore sequencing of mRNA reveals landscape of transcript isoforms in apicomplexan parasites,doi.org/10.1101/2020.02.16.946699,,,See https://www.biorxiv.org/about-biorxiv,"Alternative splicing is a widespread phenomenon in metazoans by which single genes are able to produce multiple isoforms of the gene product. However, this has been poorly characterised in apicomplexans, a major phylum of some of the most important global parasites. Efforts have been hampered by atypical transcriptomic features, such as the high AT content of Plasmodium RNA, but also the limitations of short read sequencing in deciphering complex splicing events. In this study, we utilised the long read direct RNA sequencing platform developed by Oxford Nanopore Technologies (ONT) to survey the alternative splicing landscape of Toxoplasma gondii and Plasmodium falciparum. We find that while native RNA sequencing has a reduced throughput, it allows us to obtain full-length or near full-length transcripts with comparable quantification to Illumina sequencing. By comparing this data with available gene models, we find widespread alternative splicing, particular intron retention, in these parasites. Most of these transcripts contain premature stop codons, suggesting that in these parasites, alternative splicing represents a pathway to transcriptomic diversity, rather than expanding proteomic diversity. Moreover, alternative splicing rates are comparable between parasites, suggesting a shared splicing machinery, despite notable transcriptomic differences between the parasites. This work highlights a strategy in using long read sequencing to understand splicing events at the whole transcript level, and has implications in future interpretation of RNA-seq studies.",2020-02-17,"Lee, V. V.; Judd, L.; Jex, A.; Holt, K. E.; Tonkin, C.; Ralph, S.",,,,True
3319392ca8bd2b8f2e2d00bccdb80deaa8a77c2e,biorxiv,Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China,doi.org/10.1101/2020.02.13.945485,,,See https://www.biorxiv.org/about-biorxiv,"The ongoing outbreak of viral pneumonia in China and beyond is associated with a novel coronavirus, provisionally termed 2019-nCoV. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection. Although bats are likely reservoir hosts for 2019-nCoV, the identity of any intermediate host facilitating transfer to humans is unknown. Here, we report the identification of 2019-nCoV related coronaviruses in pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin associated CoVs that belong to two sub-lineages of 2019-nCoV related coronaviruses, including one very closely related to 2019-nCoV in the receptor-binding domain. The discovery of multiple lineages of pangolin coronavirus and their similarity to 2019-nCoV suggests that pangolins should be considered as possible intermediate hosts for this novel human virus and should be removed from wet markets to prevent zoonotic transmission.",2020-02-18,"Lam, T. T.-Y.; Shum, M. H.-H.; Zhu, H.-C.; Tong, Y.-G.; Ni, X.-B.; Liao, Y.-S.; Wei, W.; Cheung, W. Y.-M.; Li, W.-J.; Li, L.-F.; Leung, G. M.; Holmes, E. C.; Hu, Y.-L.; Guan, Y.",,,,True
9e94f9379fd74fcacc4f3a57e03cbe9035efee8e,biorxiv,"Molecular Modeling Evaluation of the Binding Effect of Ritonavir, Lopinavir and Darunavir to Severe Acute Respiratory Syndrome Coronavirus 2 Proteases",doi.org/10.1101/2020.01.31.929695,,,See https://www.biorxiv.org/about-biorxiv,"Three anti-HIV drugs, ritonavir, lopinavir and darunavir, might have therapeutic effect on coronavirus disease 2019 (COVID-19). In this study, the structure models of two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteases, coronavirus endopeptidase C30 (CEP_C30) and papain like viral protease (PLVP), were built by homology modeling. Ritonavir, lopinavir and darunavir were then docked to the models, respectively, followed by energy minimization of the protease-drug complexes. In the simulations, ritonavir can bind to CEP_C30 most suitably, and induce significant conformation changes of CEP_C30; lopinavir can also bind to CEP_C30 suitably, and induce significant conformation changes of CEP_C30; darunavir can bind to PLVP suitably with slight conformation changes of PLVP. It is suggested that the therapeutic effect of ritonavir and lopinavir on COVID-19 may be mainly due to their inhibitory effect on CEP_C30, while ritonavir may have stronger efficacy; the inhibitory effect of darunavir on SARS-CoV-2 and its potential therapeutic effect may be mainly due to its inhibitory effect on PLVP.",2020-02-18,"Lin, S.; Shen, R.; He, J.; Li, X.; Guo, X.",,,,True
69008e4d4e158ae9484c3821e4384aa5948c3209,biorxiv,Recombination and convergent evolution led to the emergence of 2019 Wuhan coronavirus,doi.org/10.1101/2020.02.10.942748,,,See https://www.biorxiv.org/about-biorxiv,"The recent outbreak of a new coronavirus (2019-nCoV) in Wuhan, China, underscores the need for understanding the evolutionary processes that drive the emergence and adaptation of zoonotic viruses in humans. Here, we show that recombination in betacoronaviruses, including human-infecting viruses like SARS and MERS, frequently encompasses the Receptor Binding Domain (RBD) in the Spike gene. We find that this common process likely led to a recombination event at least 11 years ago in an ancestor of the 2019-nCoV involving the RBD. Compared with bat isolates, the recent ancestors of 2019-nCoV accumulated a high number of amino acid substitutions in the RBD and likewise in a region of polyprotein Orf1a that is critical for viral replication and transcription. Among these recent mutations, we identify amino acid substitutions common to the SARS 2003 outbreak isolates in positions 427N and 436Y, indicating potential adaptive convergent evolution. Both 427N and 436Y belong to a helix that appears to interact with the human ACE2 receptor. In sum, we propose a two-hit scenario in the emergence of the 2019-nCoV virus whereby the 2019-nCoV ancestors in bats first acquired genetic characteristics of SARS by incorporation of a SARS-like RBD through recombination before 2009, and subsequently, those recombinants underwent convergent evolution.",2020-02-18,"Patino-Galindo, J. A.; Filip, I.; AlQuraishi, M.; Rabadan, R.",,,,True
b970b7a807f37678f91d4b989ffdb7d7606d754d,biorxiv,Single-cell Analysis of ACE2 Expression in Human Kidneys and Bladders Reveals a Potential Route of 2019-nCoV Infection,doi.org/10.1101/2020.02.08.939892,,,See https://www.biorxiv.org/about-biorxiv,"Since December 2019, a novel coronavirus named 2019 coronavirus (2019-nCoV) has emerged in Wuhan of China and spread to several countries worldwide within just one month. Apart from fever and respiratory complications, acute kidney injury has been observed in some patients with 2019-nCoV. In a short period of time, angiotensin converting enzyme II (ACE2), have been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same for severe acute respiratory syndrome coronavirus (SARS). To investigate the possible cause of kidney damage in 2019-nCoV patients, we used both published kidney and bladder cell atlas data and an independent unpublished kidney single cell RNA-Seq data generated in-house to evaluate ACE2 gene expressions in all cell types in healthy kidneys and bladders.  Our results showed the enriched expression of all subtypes of proximal tubule cells of kidney and low but detectable levels of expression in bladder epithelial cells. These results indicated the urinary system is a potential route for 2019-nCoV infection, along with the respiratory system and digestion system. Our findings suggested the kidney abnormalities of SARS and 2019-nCoV patients may be due to proximal tubule cells damage and subsequent systematic inflammatory response induced kidney injury. Beyond that, laboratory tests of viruses and related indicators in urine may be needed in some special patients of 2019-nCoV.",2020-02-18,"Lin, W.; Hu, L.; Zhang, Y.; Ooi, J. D.; Meng, T.; Jin, P.; Ding, X.; Peng, L.; Song, L.; Xiao, Z.; Ao, X.; Xiao, X.; Zhou, Q.; Xiao, P.; Fan, J.; Zhong, Y.",,,,True
7ab9f9fcea519ebce527c3ede8091beedbb26ad9,biorxiv,Structural modeling of 2019-novel coronavirus (nCoV) spike protein reveals a proteolytically-sensitive activation loop as a distinguishing feature compared to SARS-CoV and related SARS-like coronaviruses,doi.org/10.1101/2020.02.10.942185,,,See https://www.biorxiv.org/about-biorxiv,"The 2019 novel coronavirus (2019-nCoV) is currently causing a widespread outbreak centered on Hubei province, China and is a major public health concern. Taxonomically 2019-nCoV is closely related to SARS-CoV and SARS-related bat coronaviruses, and it appears to share a common receptor with SARS-CoV (ACE-2). Here, we perform structural modeling of the 2019-nCoV spike glycoprotein. Our data provide support for the similar receptor utilization between 2019-nCoV and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module. Compared to SARS-CoV, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains, which we predict to be proteolytically-sensitive. We suggest this loop confers fusion activation and entry properties more in line with MERS-CoV and other coronaviruses, and that the presence of this structural loop in 2019-nCoV may affect virus stability and transmission.",2020-02-18,"Jaimes, J. A.; Andre, N. M.; Millet, J. K.; Whittaker, G. R.",,,,True
b705170c7527f5bc6842d90bf443fa9f9ee00bf9,biorxiv,Structure of dimeric full-length human ACE2 in complex with B0AT1,doi.org/10.1101/2020.02.17.951848,,,See https://www.biorxiv.org/about-biorxiv,"Angiotensin-converting enzyme 2 (ACE2) is the surface receptor for SARS coronavirus (SARS-CoV), directly interacting with the spike glycoprotein (S protein). ACE2 is also suggested to be the receptor for the new coronavirus (2019-nCoV), which is causing a serious epidemic in China manifested with severe respiratory syndrome. B0AT1 (SLC6A19) is a neutral amino acid transporter whose surface expression in intestinal cells requires ACE2. Here we present the 2.9 [A] resolution cryo-EM structure of full-length human ACE2 in complex with B0AT1. The complex, assembled as a dimer of ACE2-B0AT1 heterodimers, exhibits open and closed conformations due to the shifts of the peptidase domains (PDs) of ACE2. A newly resolved Collectrin-like domain (CLD) on ACE2 mediates homo-dimerization. Structural modelling suggests that the ACE2-B0AT1 complex can bind two S proteins simultaneously, providing important clues to the molecular basis for coronavirus recognition and infection.",2020-02-18,"Zhou, Q.; Yan, R.; Zhang, Y.; Li, Y.; Xia, L.",,,,True
a8be6ba53508e988c2c8c153478ff615b0d77687,biorxiv,Modulation of metabolic functions through Cas13d-mediated gene knockdown in liver,doi.org/10.1101/2020.02.17.945014,,,See https://www.biorxiv.org/about-biorxiv,"RNA knockdown in vivo carries significant potential for disease modelings and therapies. Despite the emerging approaches of CRISPR/Cas9-mediated permanent knock out of targeted genes, strategies targeting RNA for disruption are advantageous in the treatment of acquired metabolic disorders when permanent modification of the genome DNA is not appropriate, and RNA virus infection diseases when pathogenic DNA is not available (such as SARS-Cov-2 and MERS infections). Recently, Cas13d, a family of RNA-targeting CRISPR effectors, has been shown to accomplish robust down-regulation of cellular RNAs in mammalian cells in vitro. Among the various Cas13d subtypes, CasRx (RfxCas13d) showed the most potent RNA knockdown efficiency in HEK293T cells. However, the RNA-targeting activity of Cas13d still needs to be verified in vivo. In this study, the CasRx system was demonstrated to efficiently and functionally knock down genes related to metabolism functions, including Pten, Pcsk9 and lncLstr, in mouse hepatocytes. CasRx-mediated simultaneous knockdown of multiple genes was also achieved by sgRNA arrays, providing a useful strategy to modulate complex metabolism networks. Moreover, the AAV (adeno-associated virus)-mediated delivery of CasRx and Pcsk9 sgRNAs into mouse liver successfully decreased serum PCSK9, resulting in significant reduction of serum cholesterol levels. Importantly, CasRx-mediated knockdown of Pcsk9 is reversible and Pcsk9 could be repeatedly down-regulated, providing an effective strategy to reversibly modulate metabolic genes. The present work supplies a successful proof-of-concept trial that suggests efficient and regulatory knockdown of target metabolic genes for a designed metabolism modulation in the liver.",2020-02-19,"Huang, P.; He, B.; Peng, W.; Huang, J.; Zhang, H.; Zhou, Y.; Yang, X.; Liu, J.; Li, Z.; Xu, C.; Xue, M.; Yang, H.",,,,True
c2af4db8591a8ef84229eb08359c0a50efa24544,biorxiv,Structure and immune recognition of the porcine epidemic diarrhea virus spike protein,doi.org/10.1101/2020.02.18.955195,,,See https://www.biorxiv.org/about-biorxiv,"Porcine epidemic diarrhea virus is an alphacoronavirus responsible for significant morbidity and mortality in pigs. A key determinant of viral tropism and entry, the PEDV spike protein is a key target for the host antibody response and a good candidate for a protein-based vaccine immunogen. We used electron microscopy to evaluate the PEDV spike structure, as well as pig polyclonal antibody responses to viral infection. The structure of the PEDV spike reveals a configuration similar to that of HuCoV-NL63. Several PEDV protein-protein interfaces are mediated by non-protein components including a glycan at Asn264 and two bound palmitoleic acid molecules. The polyclonal antibody response to PEDV infection shows a dominance of epitopes in the S1 region. This structural and immune characterization provides new insights into coronavirus spike stability determinants and explores the immune landscape of viral spike proteins.",2020-02-19,"Kirchdoerfer, R.; Bhandari, M.; Martini, O.; Sewell, L. M.; Bangaru, S.; Yoon, K.-J.; Ward, A.",,,,True
3579a2b0053bef55f93716e444173727a6c94c6d,biorxiv,Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus,doi.org/10.1101/2020.02.12.945576,,,See https://www.biorxiv.org/about-biorxiv,"Pathogenic human coronavirus infections, such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV), cause high morbidity and mortality 1,2. Recently, a severe pneumonia-associated respiratory syndrome caused by a new coronavirus was reported at December 2019 (2019-nCoV) in the city Wuhan, Hubei province, China3-5, which was also named as pneumonia-associated respiratory syndrome (PARS)6. Up to 9th of February 2020, at least 37, 251 cases have been reported with 812 fatal cases according to the report from China CDC. However, the immune mechanism that potential orchestrated acute mortality from patients of 2019-nCoV is still unknown. Here we show that after the 2019-nCoV infection, CD4+T lymphocytes are rapidly activated to become pathogenic T helper (Th) 1 cells and generate GM-CSF etc. The cytokines environment induces inflammatory CD14+CD16+ monocytes with high expression of IL-6 and accelerates the inflammation. These aberrant and excessive immune cells may enter the pulmonary circulation in huge numbers and play an immune damaging role to causing lung functional disability and quick mortality. Our results demonstrate that excessive non-effective host immune responses by pathogenic T cells and inflammatory monocytes may associate with severe lung pathology. Therefore, we suggest that monoclonal antibody that targets the GM-CSF or interleukin 6 receptor may potentially curb immunopathology caused by 2019-nCoV and consequently win more time for virus clearance.",2020-02-20,"Zhou, Y.; Fu, B.; Zheng, X.; Wang, D.; Zhao, C.; Qi, Y.; Sun, R.; Tian, Z.; Xu, X.; Wei, H.",,,,True
cb3974f33a1d54369d630e62052d603148bb12e7,biorxiv,Are pangolins the intermediate host of the 2019 novel coronavirus (2019-nCoV) ?,doi.org/10.1101/2020.02.18.954628,,,See https://www.biorxiv.org/about-biorxiv,"The outbreak of 2019-nCoV pneumonia (COVID-19) in the city of Wuhan, China has resulted in more than 70,000 laboratory confirmed cases, and recent studies showed that 2019-nCoV (SARS-CoV-2) could be of bat origin but involve other potential intermediate hosts. In this study, we assembled the genomes of coronaviruses identified in sick pangolins. The molecular and phylogenetic analyses showed that pangolin Coronaviruses (pangolin-CoV) are genetically related to both the 2019-nCoV and bat Coronaviruses but do not support the 2019-nCoV arose directly from the pangolin-CoV. Our study also suggested that pangolin be natural host of Betacoronavirus, with a potential to infect humans. Large surveillance of coronaviruses in pangolins could improve our understanding of the spectrum of coronaviruses in pangolins. Conservation of wildlife and limits of the exposures of humans to wildlife will be important to minimize the spillover risks of coronaviruses from wild animals to humans.",2020-02-20,"Liu, P.; Jiang, J.-Z.; Hua, Y.; Wang, X.; Hou, F.; Wan, X.-F.; Chen, J.; Zou, J.; Chen, J.",,,,True
8390e1ea256a874142083e62635714064520d3de,biorxiv,CasRx-mediated RNA targeting prevents choroidal neovascularization in a mouse model of age-related macular degeneration,doi.org/10.1101/2020.02.18.955286,,,See https://www.biorxiv.org/about-biorxiv,"The smallest Cas13 family protein, CasRx, has a high cleavage activity and targeting specificity, offering attractive opportunity for therapeutic applications. Here we report that delivery of CasRx by adeno-associated virus via intravitreal injection could efficiently knockdown Vegfa transcripts and significantly reduce the area of laser-induced choroidal neovascularization in a mouse model of age-related macular degeneration. Thus, RNA-targeting CRISPR system could be used for in vivo gene therapy.",2020-02-20,"Zhou, C.; Hu, X.; Tang, C.; Liu, W.; Wang, S.; Zhou, Y.; Zhao, Q.; Bo, Q.; Shi, L.; Sun, X.; Zhou, H.; Yang, H.",,,,False
1162f8e5f4f341543d43e7ff08d2fc02900fd3c6,biorxiv,Crystal structure of the 2019-nCoV spike receptor-binding domain bound with the ACE2 receptor,doi.org/10.1101/2020.02.19.956235,,,See https://www.biorxiv.org/about-biorxiv,"A novel and highly pathogenic coronavirus (2019-nCoV) has caused an outbreak in Wuhan city, Hubei province of China since December 2019, and soon spread nationwide and spilled over to other countries around the world. To better understand the initial step of infection at atomic-level, we determined the crystal structure of the 2019-nCoV spike receptor-binding domain (RBD) bound with the cell receptor ACE2 at 2.45 [A] resolution. The overall ACE2-binding mode of the 2019-nCoV RBD is nearly identical to that of the SARS-CoV RBD, which also utilizes ACE2 as the cell receptor. Structural analysis identified residues in 2019-nCoV RBD critical for ACE2 binding, and majority of which are either highly conserved or shared similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly argue for a convergent evolution between 2019-nCoV and SARS-CoV RBD for improved binding to ACE2 despite of being segregated in different genetic lineages in the betacoronavirus genus. The epitopes of two SARS-CoV antibodies targeting the RBD are also analyzed with the 2019-nCoV RBD, providing insights into future identification of cross-reactive antibodies.",2020-02-20,"Lan, J.; Ge, J.; Yu, J.; Shan, S.; Zhou, H.; Fan, S.; Zhang, Q.; Shi, X.; Wang, Q.; Zhang, L.; Wang, X.",,,,False
1fb563e0f5960e0015a5863d8791fc8717eb4173,biorxiv,Isolation and Characterization of 2019-nCoV-like Coronavirus from Malayan Pangolins,doi.org/10.1101/2020.02.17.951335,,,See https://www.biorxiv.org/about-biorxiv,"The outbreak of 2019-nCoV in the central Chinese city of Wuhan at the end of 2019 poses unprecedent public health challenges to both China and the rest world1. The new coronavirus shares high sequence identity to SARS-CoV and a newly identified bat coronavirus2. While bats may be the reservoir host for various coronaviruses, whether 2019-nCoV has other hosts is still ambiguous. In this study, one coronavirus isolated from Malayan pangolins showed 100%, 98.2%, 96.7% and 90.4% amino acid identity with 2019-nCoV in the E, M, N and S genes, respectively. In particular, the receptor-binding domain of the S protein of the Pangolin-CoV is virtually identical to that of 2019-nCoV, with one amino acid difference. Comparison of available genomes suggests 2019-nCoV might have originated from the recombination of a Pangolin-CoV-like virus with a Bat-CoV-RaTG13-like virus. Infected pangolins showed clinical signs and histopathological changes, and the circulating antibodies reacted with the S protein of 2019-nCoV. The isolation of a coronavirus that is highly related to 2019-nCoV in the pangolins suggests that these animals have the potential to act as the intermediate host of 2019-nCoV. The newly identified coronavirus in the most-trafficked mammal could represent a continuous threat to public health if wildlife trade is not effectively controlled.",2020-02-20,"Xiao, K.; Zhai, J.; Feng, Y.; Zhou, N.; Zhang, X.; Zou, J.-J.; Li, N.; Guo, Y.; Li, X.; Shen, X.; Zhang, Z.; Shu, F.; Huang, W.; Li, Y.; Zhang, Z.; Chen, R.-A.; Wu, Y.-J.; Peng, S.-M.; Huang, M.; Xie, W.-J.; Cai, Q.-H.; Hou, F.-H.; Liu, Y.; Chen, W.; Xiao, L.; Shen, Y.",,,,False
bb8e3d331bb2975e1c644c8729b842797da2d626,biorxiv,Machine learning using intrinsic genomic signatures for rapid classification of novel pathogens: COVID-19 case study,doi.org/10.1101/2020.02.03.932350,,,See https://www.biorxiv.org/about-biorxiv,"As of February 20, 2020, the 2019 novel coronavirus (renamed to COVID-19) spread to 30 countries with 2130 deaths and more than 75500 confirmed cases. COVID-19 is being compared to the infamous SARS coronavirus, which resulted, between November 2002 and July 2003, in 8098 confirmed cases worldwide with a 9.6% death rate and 774 deaths. Though COVID-19 has a death rate of 2.8% as of 20 February, the 75752 confirmed cases in a few weeks (December 8, 2019 to February 20, 2020) are alarming, with cases likely being under-reported given the comparatively longer incubation period. Such outbreaks demand elucidation of taxonomic classification and origin of the virus genomic sequence, for strategic planning, containment, and treatment. This paper identifies an intrinsic COVID-19 genomic signature and uses it together with a machine learning-based alignment-free approach for an ultra-fast, scalable, and highly accurate classification of whole COVID-19 genomes. The proposed method combines supervised machine learning with digital signal processing for genome analyses, augmented by a decision tree approach to the machine learning component, and a Spearmans rank correlation coefficient analysis for result validation. These tools are used to analyze a large dataset of over 5000 unique viral genomic sequences, totalling 61.8 million bp. Our results support a hypothesis of a bat origin and classify COVID-19 as Sarbecovirus, within Betacoronavirus. Our method achieves high levels of classification accuracy and discovers the most relevant relationships among over 5,000 viral genomes within a few minutes, ab initio, using raw DNA sequence data alone, and without any specialized biological knowledge, training, gene or genome annotations. This suggests that, for novel viral and pathogen genome sequences, this alignment-free whole-genome machine-learning approach can provide a reliable real-time option for taxonomic classification.",2020-02-20,"Randhawa, G. S.; Soltysiak, M. P. M.; El Roz, H.; de Souza, C. P. E.; Hill, K. A.; Kari, L.",,,,True
70c7260fc0702bd4a554421ac68972c991313e56,biorxiv,Mucin 4 Protects Female Mice from Coronavirus Pathogenesis,doi.org/10.1101/2020.02.19.957118,,,See https://www.biorxiv.org/about-biorxiv,"Using incipient lines of the Collaborative Cross (CC), a murine genetic reference population, we previously identified a quantitative trait loci (QTL) associated with low SARS-CoV titer. In this study, we integrated sequence information and RNA expression of genes within the QTL to identify mucin 4 (Muc4) as a high priority candidate for controlling SARS-CoV titer in the lung. To test this hypothesis, we infected Muc4-/- mice and found that female, but not male, Muc4-/- mice developed more weight loss and disease following infection with SARS-CoV. Female Muc4-/- mice also had more difficulty breathing despite reduced lung pathology; however, no change in viral titers was observed. Comparing across viral families, studies with chikungunya virus, a mosquito-borne arthralgic virus, suggests that Muc4s impact on viral pathogenesis may be widespread. Although not confirming the original titer QTL, our data identifies a role for Muc4 in the SARS-CoV disease and viral pathogenesis.  ImportanceGiven the recent emergence of SARS-CoV-2, this work suggest that Muc4 expression plays a protective role in female mice not conserved in male mice following SARS-CoV infection. With the SARS-CoV-2 outbreak continuing, treatments that modulate or enhance Muc4 activity may provide an avenue for treatment and improved outcomes. In addition, the work highlights the importance of studying host factors including host genetics and biological sex as key parameters influencing infection and disease outcomes.",2020-02-20,"Plante, J. A.; Plante, K.; Gralinski, L.; Beall, A.; Ferris, M. T.; Bottomly, D.; Green, R. R.; McWeeney, S.; Heise, M. T.; Baric, R. S.; Menachery, V. D.",,,,True
aa507fcd3876f8c422993c8dd13847b1b8e77471,biorxiv,Pangolin homology associated with 2019-nCoV,doi.org/10.1101/2020.02.19.950253,,,See https://www.biorxiv.org/about-biorxiv,"To explore potential intermediate host of a novel coronavirus is vital to rapidly control continuous COVID-19 spread. We found genomic and evolutionary evidences of the occurrence of 2019-nCoV-like coronavirus (named as Pangolin-CoV) from dead Malayan Pangolins. Pangolin-CoV is 91.02% and 90.55% identical at the whole genome level to 2019-nCoV and BatCoV RaTG13, respectively. Pangolin-CoV is the lowest common ancestor of 2019-nCoV and RaTG13. The S1 protein of Pangolin-CoV is much more closely related to 2019-nCoV than RaTG13. Five key amino-acid residues involved in the interaction with human ACE2 are completely consistent between Pangolin-CoV and 2019-nCoV but four amino-acid mutations occur in RaTG13. It indicates Pangolin-CoV has similar pathogenic potential to 2019-nCoV, and would be helpful to trace the origin and probable intermediate host of 2019-nCoV.",2020-02-20,"Zhang, Z.; Wu, Q.; Zhang, T.",,,,True
a388cca261e8af7936cf3b79c35f43442f65706b,biorxiv,SARS-CoV-2 and SARS-CoV Spike-RBD Structure and Receptor Binding Comparison and Potential Implications on Neutralizing Antibody and Vaccine Development,doi.org/10.1101/2020.02.16.951723,,,See https://www.biorxiv.org/about-biorxiv,"SARS-CoV-2 and SARS-CoV share a common human receptor ACE2. Protein-protein interaction structure modeling indicates that spike-RBD of the two viruses also has similar overall binding conformation and binding free energy to ACE2. In vitro assays using recombinant ACE2 proteins and ACE2 expressing cells confirmed the two coronaviruses similar binding affinities to ACE2. The above studies provide experimental supporting evidences and possible explanation for the high transmissibility observed in the SARS-CoV-2 outbreak. Potent ACE2-blocking SARS-CoV neutralizing antibodies showed limited cross-binding and neutralizing activities to SARS-CoV-2. ACE2-non-blocking SARS-CoV RBD antibodies, though with weaker neutralizing activities against SARS-CoV, showed positive cross-neutralizing activities to SARS-CoV-2 with an unknown mechanism. These findings suggest a trade-off between the efficacy and spectrum for therapeutic antibodies to different coronaviruses, and hence highlight the possibilities and challenges in developing broadly protecting antibodies and vaccines against SARS-CoV-2 and its future mutants.",2020-02-20,"Xie, L.; Sun, C.; Luo, C.; Zhang, Y.; Zhang, J.; Yang, J.; Chen, L.; Yang, J.; Li, J.",,,,True
3a6544f6f247366d4c12167f7fba743e9d981c63,biorxiv,Structural basis for the recognition of the 2019-nCoV by human ACE2,doi.org/10.1101/2020.02.19.956946,,,See https://www.biorxiv.org/about-biorxiv,"Angiotensin-converting enzyme 2 (ACE2) has been suggested to be the cellular receptor for the new coronavirus (2019-nCoV) that is causing the coronavirus disease 2019 (COVID-19). Like other coronaviruses such as the SARS-CoV, the 2019-nCoV uses the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) to engage ACE2. We most recently determined the structure of the full-length human ACE2 in complex with a neutral amino acid transporter B0AT1. Here we report the cryo-EM structure of the full-length human ACE2 bound to the RBD of the 2019-nCoV at an overall resolution of 2.9 [A] in the presence of B0AT1. The local resolution at the ACE2-RBD interface is 3.5 [A], allowing analysis of the detailed interactions between the RBD and the receptor. Similar to that for the SARS-CoV, the RBD of the 2019-nCoV is recognized by the extracellular peptidase domain (PD) of ACE2 mainly through polar residues. Pairwise comparison reveals a number of variations that may determine the different affinities between ACE2 and the RBDs from these two related viruses.",2020-02-20,"Yan, R.; Zhang, Y.; Guo, Y.; Xia, L.; Zhou, Q.",,,,True
82ccfacf2b8709daa2532f914b22d84818e15eba,biorxiv,"Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein",doi.org/10.1101/2020.02.19.956581,,,See https://www.biorxiv.org/about-biorxiv,"The recent emergence of a novel coronavirus associated with an ongoing outbreak of pneumonia (Covid-2019) resulted in infections of more than 72,000 people and claimed over 1,800 lives. Coronavirus spike (S) glycoprotein trimers promote entry into cells and are the main target of the humoral immune response. We show here that SARS-CoV-2 S mediates entry in VeroE6 cells and in BHK cells transiently transfected with human ACE2, establishing ACE2 as a functional receptor for this novel coronavirus. We further demonstrate that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, which correlates with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and other SARS-related CoVs. We determined a cryo-electron microscopy structure of the SARS-CoV-2 S ectodomain trimer, demonstrating spontaneous opening of the receptor-binding domain, and providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal sera potently inhibited SARS-CoV-2 S-mediated entry into target cells, thereby indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.",2020-02-20,"Walls, A. C.; Park, Y.-J.; Tortorici, M. A.; Wall, A.; McGuire, A. T.; Veesler, D.",,,,False
cc5e36a8d22f6b1708b1c43764806b1722aa1754,biorxiv,X-ray Structure of Main Protease of the Novel Coronavirus SARS-CoV-2 Enables Design of α-Ketoamide Inhibitors,doi.org/10.1101/2020.02.17.952879,,,See https://www.biorxiv.org/about-biorxiv,"A novel coronavirus has been identified as the causative agent of a massive outbreak of atypical pneumonia originating at Wuhan, Hubei province, China. Involved in the formation of the coronavirus replication complex, the viral main protease (Mpro, also called 3CLpro) represents an attractive target for therapy. We determined the crystal structure of the unliganded Mpro at 1.75 [A] resolution and used this structure to guide optimization of a series of alpha-ketoamide inhibitors. The main goal of the optimization efforts was improvement of the pharmacokinetic properties of the compounds. We further describe 1.95- and 2.20-[A] crystal structures of the complex between the enzyme and the most potent alpha-ketoamide optimized this way. These structures will form the basis for further development of these compounds to antiviral drugs.",2020-02-20,"Zhang, L.; Lin, D.; Sun, X.; Rox, K.; Hilgenfeld, R.",,,,True
78e49fdb6f0aa9924a5b510341d52b618fff0ca6,biorxiv,A Multiscale and Comparative Model for Receptor Binding of 2019 Novel Coronavirus and the Implication of its Life Cycle in Host Cells,doi.org/10.1101/2020.02.20.958272,,,See https://www.biorxiv.org/about-biorxiv,"The respiratory syndrome caused by a new type of coronavirus has been emerging from China and caused more than 1000 death globally since December 2019. This new virus, called 2019 novel coronavirus (2019-nCoV) uses the same receptor called Angiotensinconverting enzyme 2 (ACE2) to attack humans as the coronavirus that caused the severe acute respiratory syndrome (SARS) seventeen years ago. Both viruses recognize ACE2 through the spike proteins (S-protein) on their surfaces. It was found that the S-protein from the SARS coronavirus (SARS-CoV) bind stronger to ACE2 than 2019-nCoV. However, function of a bio-system is often under kinetic, rather than thermodynamic, control. To address this issue, we constructed a structural model for complex formed between ACE2 and the S-protein from 2019-nCoV, so that the rate of their association can be estimated and compared with the binding of S-protein from SARS-CoV by a multiscale simulation method. Our simulation results suggest that the association of new virus to the receptor is slower than SARS, which is consistent with the experimental data obtained very recently. We further integrated this difference of association rate between virus and receptor into a mathematical model which describes the life cycle of virus in host cells and its interplay with the innate immune system. Interestingly, we found that the slower association between virus and receptor can result in longer incubation period, while still maintaining a relatively higher level of viral concentration in human body. Our computational study therefore provides, from the molecular level, one possible explanation that the new disease by far spread much faster than SARS.",2020-02-21,"Su, Z.; Wu, Y.",,,,True
e7cd4d013ea2170672460a4c45cbcf3a609eecfb,biorxiv,Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV),doi.org/10.1101/2020.02.17.952903,,,See https://www.biorxiv.org/about-biorxiv,"Since December, 2019, an outbreak of pneumonia caused by the new coronavirus (2019-nCoV) has hit the city of Wuhan in the Hubei Province. With the continuous development of the epidemic, it has become a national public health crisis and calls for urgent antiviral treatments or vaccines. The spike protein on the coronavirus envelope is critical for host cell infection and virus vitality. Previous studies showed that 2019-nCoV is highly homologous to human SARS-CoV and attaches host cells though the binding of the spike receptor binding domain (RBD) domain to the angiotensin-converting enzyme II (ACE2). However, the molecular mechanisms of 2019-nCoV binding to human ACE2 and evolution of 2019-nCoV remain unclear. In this study, we have extensively studied the RBD-ACE2 complex, spike protein, and free RBD systems of 2019-nCoV and SARS-CoV using protein-protein docking and molecular dynamics (MD) simulations. It was shown that the RBD-ACE2 binding free energy for 2019-nCoV is significantly lower than that for SARS-CoV, which is consistent with the fact that 2019-nCoV is much more infectious than SARS-CoV. In addition, the spike protein of 2019-nCoV shows a significantly lower free energy than that of SARS-CoV, suggesting that 2019-nCoV is more stable and able to survive a higher temperature than SARS-CoV. This may also provide insights into the evolution of 2019-nCoV because SARS-like coronaviruses are thought to have originated in bats that are known to have a higher body-temperature than humans. It was also revealed that the RBD of 2019-nCoV is much more flexible especially near the binding site and thus will have a higher entropy penalty upon binding ACE2, compared to the RBD of SARS-CoV. That means that 2019-nCoV will be much more temperature-sensitive in terms of human infection than SARS-CoV. With the rising temperature, 2019-nCoV is expected to decrease its infection ability much faster than SARS-CoV, and get controlled more easily. The present findings are expected to be helpful for the disease prevention and control as well as drug and vaccine development of 2019-nCoV.",2020-02-21,"He, J.; Tao, H.; Yan, Y.; Huang, S.-Y.; Xiao, Y.",,,,False
b38ed62b303eaa444d188deb2ab0b23bbdb79211,biorxiv,Potential T-cell and B-cell Epitopes of 2019-nCoV,doi.org/10.1101/2020.02.19.955484,,,See https://www.biorxiv.org/about-biorxiv,"As of Feb 16th 2020, 2019-nCoV has infected more than 51,857 people across 26 countries and claimed 1666 lives. 2019-nCoV is a novel form of coronavirus that causes COVID-19 and has high similarity with SARS-CoV. No approved vaccine yet exists for 2019-nCoV or any form of coronavirus. Here we use computational tools from structural biology and machine learning to identify 2019-nCoV T-cell and B-cell epitopes based on viral protein antigen presentation and antibody binding properties. These epitopes can be used to develop more effective vaccines and identify neutralizing antibodies. We identified 405 viral peptides with good antigen presentation scores for both human MHC-I and MHC-II alleles, and two potential neutralizing B-cell epitopes near the 2019-nCoV spike protein receptor binding domain (440-460 and 494-506). Analyzing mutation profiles of 68 viral genomes from four continents, we identified 96 coding-change mutations. These mutations are more likely to occur in regions with good MHC-I presentation scores (p=0.02). No mutations are present near the spike protein receptor binding domain. We validated our computational pipeline with SARS-CoV experimental data.",2020-02-21,"Fast, E.; Chen, B.",,,,True
8bba09a1353fca83e21c4acaa9eed9f39f21cabe,biorxiv,Protection of Rhesus Macaque from SARS-Coronavirus challenge by recombinant adenovirus vaccine,doi.org/10.1101/2020.02.17.951939,,,See https://www.biorxiv.org/about-biorxiv,"A recombinant adenovirus vaccine against the SARS Coronavirus (SARS-CoV) was constructed, which contains fragments from the S, N, and Orf8 genes. Rhesus Macaques immunized with the recombinant adenovirus generated antigen-specific humoral and cellular response. Furthermore, the vaccine provided significant protection against subsequent live SARS-CoV challenge. In contrast, three out of four monkeys immunized with placebo suffered severe alveolar damage and pulmonary destruction.",2020-02-21,"Chen, Y.; Qin, C.; Wei, Q.; Li, R.; Gao, H.; Zhu, H.; Deng, W.; Bao, L.; Wei, T.",,,,False
b9da9ffc87686c0c27666e5d6a9009b7f8b6289a,biorxiv,Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform,doi.org/10.1101/2020.02.21.959817,,,See https://www.biorxiv.org/about-biorxiv,"Reverse genetics has been an indispensable tool revolutionising our insights into viral pathogenesis and vaccine development. Large RNA virus genomes, such as from Coronaviruses, are cumbersome to clone and to manipulate in E. coli hosts due to size and occasional instability1-3. Therefore, an alternative rapid and robust reverse genetics platform for RNA viruses would benefit the research community. Here we show the full functionality of a yeast-based synthetic genomics platform for the genetic reconstruction of diverse RNA viruses, including members of the Coronaviridae, Flaviviridae and Paramyxoviridae families. Viral subgenomic fragments were generated using viral isolates, cloned viral DNA, clinical samples, or synthetic DNA, and reassembled in one step in Saccharomyces cerevisiae using transformation associated recombination (TAR) cloning to maintain the genome as a yeast artificial chromosome (YAC). T7-RNA polymerase has been used to generate infectious RNA, which was then used to rescue viable virus. Based on this platform we have been able to engineer and resurrect chemically-synthetized clones of the recent epidemic SARS-CoV-24 in only a week after receipt of the synthetic DNA fragments. The technical advance we describe here allows to rapidly responding to emerging viruses as it enables the generation and functional characterization of evolving RNA virus variants - in real-time - during an outbreak.",2020-02-21,"Thao, T. T. N.; Labroussaa, F.; Ebert, N.; V'kovski, P.; Stalder, H.; Portmann, J.; Kelly, J.; Steiner, S.; Holwerda, M.; Kratzel, A.; Gultom, M.; Laloli, L.; Huesser, L.; Wider, M.; Pfaender, S.; Hirt, D.; Cippa, V.; Crespo-Pomar, S.; Schroeder, S.; Muth, D.; Niemeyer, D.; Mueller, M. A.; Drosten, C.; Dijkman, R.; Jores, J.; Thiel, V.",,,,False
22f3be8bbf6d792549b7a6088df7440e425cb34f,biorxiv,Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses,doi.org/10.1101/2020.02.16.951913,,,See https://www.biorxiv.org/about-biorxiv,"The new coronavirus (2019-nCoV) outbreak from December 2019 in Wuhan, Hubei, China, has been declared a global public health emergency. Angiotensin I converting enzyme 2 (ACE2), is the host receptor by 2019-nCov to infect human cells. Although ACE2 is reported to be expressed in lung, liver, stomach, ileum, kidney and colon, its expressing levels are rather low, especially in the lung. 2019-nCoV may use co-receptors/auxiliary proteins as ACE2 partner to facilitate the virus entry. To identify the potential candidates, we explored the single cell gene expression atlas including 119 cell types of 13 human tissues and analyzed the single cell co-expression spectrum of 51 reported RNA virus receptors and 400 other membrane proteins. Consistent with other recent reports, we confirmed that ACE2 was mainly expressed in lung AT2, liver cholangiocyte, colon colonocytes, esophagus keratinocytes, ileum ECs, rectum ECs, stomach epithelial cells, and kidney proximal tubules. Intriguingly, we found that the candidate co-receptors, manifesting the most similar expression patterns with ACE2 across 13 human tissues, are all peptidases, including ANPEP, DPP4 and ENPEP. Among them, ANPEP and DPP4 are the known receptors for human CoVs, suggesting ENPEP as another potential receptor for human CoVs. We also conducted ""CellPhoneDB"" analysis to understand the cell crosstalk between CoV-targets and their surrounding cells across different tissues. We found that macrophages frequently communicate with the CoVs targets through chemokine and phagocytosis signaling, highlighting the importance of tissue macrophages in immune defense and immune pathogenesis.",2020-02-21,"Qi, F.; Qian, S.; Zhang, S.; Zhang, Z.",,,,True
d01e580a45c457c7c200cd884e746b4d836e2ea9,biorxiv,Vulnerabilities in coronavirus glycan shields despite extensive glycosylation,doi.org/10.1101/2020.02.20.957472,,,See https://www.biorxiv.org/about-biorxiv,"Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential. Vaccine development has focussed on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein, which mediates receptor recognition and membrane fusion. Coronavirus S proteins are extensively glycosylated viral fusion proteins, encoding around 69-87 N-linked glycosylation sites per trimeric spike. Using a multifaceted structural approach, we reveal a specific area of high glycan density on MERS S that results in the formation of under-processed oligomannose-type glycan clusters, which was absent on SARS and HKU1 CoVs. We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes. Consistent with the ability of the antibody-mediated immune response to effectively target and neutralize coronaviruses, we demonstrate that the glycans of coronavirus spikes are not able to form an efficacious high-density global shield to thwart the humoral immune response. Overall, our data reveal how differential organisation of viral glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the viral protein surface.",2020-02-21,"Watanabe, Y.; Berndsen, Z. T.; Raghwani, J.; Seabright, G. E.; Allen, J. D.; McLellan, J. S.; Wilson, I. A.; Bowden, T. A.; Ward, A. B.; Crispin, M.",,,,True
9aef9e1c22896809852ec6c94e413aff33b3d9cf,biorxiv,Inactivating porcine coronavirus before nuclei acid isolation with the temperature higher than 56 °C damages its genome integrity seriously,doi.org/10.1101/2020.02.20.958785,,,See https://www.biorxiv.org/about-biorxiv,"2019-Novel Coronavirus (2019-nCoV) is the pathogen of Corona Virus Disease 2019. Nucleic acid detection of 2019-nCoV is one of the key indicators for clinical diagnosis. However, the positive rate is only 30-50%. Currently, fluorescent quantitative RT-PCR technology is mainly used to detect 2019-nCoV. According to ""The Laboratory Technical Guidelines for Detection 2019-nCoV (Fourth Edition)"" issued by National Health and Commission of China and ""The Experts Consensus on Nucleic Acid Detection of 2019-nCoV"" released by Chinese Society of Laboratory Medicine, the human samples must be placed under 56{degrees}C or higher to inactivate the viruses in order to keep the inspectors from virus infection before the nucleic acids were isolated as the template of qRT-PCR. In this study, we demonstrated that the virus inactivation treatment disrupts its genome integrity seriously when using porcine epidemic diarrhea virus (vaccine), a kind of coronavirus, as a model. Our results showed that only 50.11% of the detectable viral templates left after the inactivation of 56 {degrees}C for 30 minutes and only 3.36% left after the inactivation of 92 {degrees}C for 5 minutes when the samples were preserved by Hanks solution, one of an isotonic salt solutions currently suggested. However, the detectable templates of viral nucleic acids can be unchanged after the samples were incubated at 56 {degrees}C or higher if the samples were preserved with an optimized solution to protect the RNA from being disrupted. We therefore highly recommend to carry out systematic investigation on the impact of high temperature inactivation on the integrity of 2019-nCoV genome and develop a sample preservation solution to protect the detectable templates of 2019-nCoV nucleic acids from high temperature inactivation damage.",2020-02-22,"Zhang, Q.; Zhao, Q.",,,,True
c55c92481de42668c67f0ef7da1431c70874075e,biorxiv,Molecular Survey for Selected Viral Pathogens in Wild Leopard Cats (Prionailurus bengalensis) in Taiwan with an Emphasis on the Spatial and Temporal Dynamics of Carnivore Protoparvovirus 1,doi.org/10.1101/2020.02.21.960492,,,See https://www.biorxiv.org/about-biorxiv,"The leopard cat (Prionailurus bengalensis) has been listed as an endangered species under the Wildlife Conservation Act in Taiwan since 2009. In this study, we targeted viral pathogens, included carnivore protoparvovirus 1 (CPPV-1), feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), coronavirus (CoV), and canine morbillivirus (CMV), using molecular screening. The spatial and temporal dynamics of the target pathogens were evaluated. Through sequencing and phylogenetic analysis, we aimed to clarify the phylogenetic relationship of isolated viral pathogens between leopard cats and domestic carnivores. Samples from 23 and 29 leopard cats that were live-trapped and found dead, respectively, were collected from Miaoli County from 2015 to 2019 in northwestern Taiwan. CPPV-1 and coronavirus were detected in leopard cats. The prevalence (95% confidence interval) of CPPV-1, and CoV was 63.5% (50.4%-76.6%) and 8.8% (0%-18.4%), respectively. The majority of sequences of each CPPV-1 strain amplified from Taiwanese leopard cats and domestic carnivores were identical. All the amplified CoV sequences from leopard cats were identified as feline coronavirus. The spatial and temporal aggregation of CPPV-1 infection in leopard cats was not determined in the sampling area, which indicated a wide distribution of CPPV-1 in the leopard cat habitat. We consider sympatric domestic carnivores to be the probable primary reservoir for the pathogens identified. We strongly recommend establishing efforts to manage CPPV-1 and FCoV in the leopard cat habitat, with an emphasis on vaccination programs and population control measures for free-roaming dogs and cats.  IMPORTANCEThe leopard cat (Prionailurus bengalensis) is an endangered species in Taiwan. The effects of infectious diseases on the wildlife population have increasingly been recognized. In this study, we targeted highly pathogenic viral pathogens in wild cat species, included carnivore protoparvovirus 1 (CPPV-1), feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), coronavirus (CoV), and canine morbillivirus (CMV), using molecular screening. Furthermore, we collected the epidemiological and phylogenetic data to understand the spatial and temporal dynamics of the target pathogens in the wild leopard cat population and identified the possible origin of target pathogens. Based on our study, we consider sympatric domestic carnivores to be the probable primary reservoir for the pathogens identified. Our study provides a deeper understanding related to the distribution of target viral pathogens in the wild leopard cats. The information is essential for leopard cat conservation and pathogen management.",2020-02-23,"Chen, C.-C.; Chang, A.-M.; Chen, W.-J.; Chang, P.-J.; Lai, Y.-C.; Lee, H.-H.",,,,False
09b6706748f0c1ae0da436ac2dfac9052b84e4ea,biorxiv,Cryo-EM structures of HKU2 and SADS-CoV spike glycoproteins and insights into coronavirus evolution,doi.org/10.1101/2020.02.23.961912,,,See https://www.biorxiv.org/about-biorxiv,"A new porcine coronavirus SADS-CoV was recently identified from suckling piglets with severe diarrhea in southern China and its genome sequence is most identical (~95% identity) to that of bat -coronavirus HKU2. It again indicates bats are the natural reservoir of many coronaviruses that have great potential for cross-species transmission to animals and humans by recombination and/or mutation. Here we report the cryo-EM structures of HKU2 and SADS-CoV spike glycoprotein trimers at 2.38 [A] and 2.83 [A] resolution, respectively. HKU2 and SADS-CoV spikes exhibit very high structural similarity, with subtle differences mainly distributed in the NTD and CTD of the S1 subunit responsible for cell attachment and receptor binding. We systematically analyzed and compared the NTD, CTD, SD1 and SD2 domains of the S1 subunit and the S2 subunit of HKU2 spike with those of -, {beta}-, {gamma}-, and {delta}-coronavirus spikes. The results show that the NTD and CTD of HKU2/SADS-CoV are probably the most ancestral in the evolution of spike. Although the S2 subunit mediating membrane fusion is highly conserved, the connecting region after fusion peptide in HKU2/SADS-CoV S2 subunit also adopts a conformation distinct from other coronaviruses. These results structurally demonstrate a close evolutionary relationship between HKU2 /SADS-CoV and {beta}-coronavirus spikes and provide new insights into the evolution and cross-species transmission of coronaviruses.",2020-02-24,"Yu, J.; Qiao, S.; Guo, R.; Wang, X.",,,,True
70da59457fb7b31cd5ee5754c94ccb41008ca117,biorxiv,IFN-{lambda}4 increases the risk of gastrointestinal infections and malaria in Malian children,doi.org/10.1101/2020.02.24.962688,,,See https://www.biorxiv.org/about-biorxiv,"Genetic polymorphisms within the IFNL3/IFNL4 genomic region encoding type III interferons have been strongly associated with impaired clearance of hepatitis C virus (HCV) infection. We hypothesized that this association might extend to the immune response to other pathogens as well. In a cohort of 914 Malian children enrolled at birth, we analyzed episodes of malaria, gastrointestinal and respiratory infections in relation to two genetic polymorphisms functionally affecting type III interferons - rs368234815 (IFN-{lambda}4) and rs4803217 (IFN-{lambda}3), using information for 30,626 clinic visits from birth through 1-5 years of follow-up. Compared to children with the rs368234815-TT/TT genotype (IFN-{lambda}4-Null), each copy of the rs368234815-dG allele was associated with an earlier first episode of a gastrointestinal infection (p=0.004), malaria (p=0.044) or respiratory infection (p=0.045). The risk of ever experiencing an infection during the follow-up was also significantly increased with each copy of the rs368234815-dG allele - for gastrointestinal infections (OR=1.5, 95%CI (1.11-2.03), p=0.0079) and malaria (OR=1.32, 95%CI (1.04-1.68, p=0.022), but not respiratory infections (p=0.58). IFNL4-rs368234815 and IFNL3-rs4803217 were in moderate linkage disequilibrium in this population (r2=0.78). All the associations for rs4803217 were weaker and lost significance after adjusting for rs368234815, implicating IFN-{lambda}4 and not IFN-{lambda}3 as the primary cause of these associations. Thus, our results suggest the role of IFN-{lambda}4 in several infections in young children.",2020-02-25,"Prokunina-Olsson, L.; Morrison, R. L.; Obajemu, A.; Mahamar, A.; Kim, S.; Attaher, O.; Florez-Vargas, O.; Sidibe, Y.; Onabajo, O. O.; Hutchinson, A. A.; Manning, M.; Kwan, J.; Brand, N.; Dicko, A.; Fried, M.; Albert, P. S.; Mbulaiteye, S. M.; Duffy, P. E.",,,,False
1df9ce60e358f6cef0be3f6e15fe2a9c6f93f39c,biorxiv,Multivariate Analyses of Codon Usage of SARS-CoV-2 and other betacoronaviruses,doi.org/10.1101/2020.02.15.950568,,,See https://www.biorxiv.org/about-biorxiv,"Coronavirus disease 2019 (COVID-19) is a global health concern as it continues to spread within China and beyond. The causative agent of this disease, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belongs to the genus Betacoronavirus which also includes severe acute respiratory syndrome related coronavirus (SARSr-CoV) and Middle East respiratory syndrome related coronavirus (MERSr-CoV). Codon usage of viral genes are believed to be subjected to different selection pressures in different host environments. Previous studies on codon usage of influenza A viruses can help identify viral host origins and evolution trends, however, similar studies on coronaviruses are lacking. In this study, global correspondence analysis (CA), within-group correspondence analysis (WCA) and between-group correspondence analysis (BCA) were performed among different genes in coronavirus viral sequences. The amino acid usage pattern of SARS-CoV-2 was generally found similar to bat and human SARSr-CoVs. However, we found greater synonymous codon usage differences between SARS-CoV-2 and its phylogenetic relatives on spike and membrane genes, suggesting these two genes of SARS-CoV-2 are subjected to different evolutionary pressures.",2020-02-25,"Gu, H.; Chu, D. K. W.; Peiris, J. S. M.; Poon, L. L. M.",,,,True
cc41c51293ed24a57ddf467e462ec9399463ee33,biorxiv,No more business as usual: agile and effective responses to emerging pathogen threats require open data and open analytics,doi.org/10.1101/2020.02.21.959973,,,See https://www.biorxiv.org/about-biorxiv,"The current state of much of the Wuhan pneumonia virus (COVID-19) research shows a regrettable lack of data sharing and considerable analytical obfuscation. This impedes global research cooperation, which is essential for tackling public health emergencies, and requires unimpeded access to data, analysis tools, and computational infrastructure. Here we show that community efforts in developing open analytical software tools over the past ten years, combined with national investments into scientific computational infrastructure, can overcome these deficiencies and provide an accessible platform for tackling global health emergencies in an open and transparent manner. Specifically, we use all COVID-19 genomic data available in the public domain so far to (1) underscore the importance of access to raw data and to (2) demonstrate that existing community efforts in curation and deployment of biomedical software can reliably support rapid, reproducible research during global health crises. All our analyses are fully documented at https://github.com/galaxyproject/SARS-CoV-2.",2020-02-25,"Galaxy and HyPhy developments teams,  ; Nekrutenko, A.; Kosakovsky Pond, S. L.",,,,True
7207df5b61e93fa5a2b6e720c91aed05270e81be,biorxiv,A simple magnetic nanoparticles-based viral RNA extraction method for efficient detection of SARS-CoV-2,doi.org/10.1101/2020.02.22.961268,,,See https://www.biorxiv.org/about-biorxiv,"1The ongoing outbreak of the novel coronavirus disease 2019 (COVID-19) originating from Wuhan, China, draws worldwide concerns due to its long incubation period and strong infectivity. Although RT-PCR-based molecular diagnosis techniques are being widely applied for clinical diagnosis currently, timely and accurate diagnosis are still limited due to labour intensive and time-consuming operations of these techniques. To address the issue, herein we report the synthesis of poly (amino ester) with carboxyl groups (PC)-coated magnetic nanoparticles (pcMNPs), and the development of pcMNPs-based viral RNA extraction method for the sensitive detection of COVID-19 causing virus, the SARS-CoV-2. This method combines the lysis and binding steps into one step, and the pcMNPs-RNA complexes can be directly introduced into subsequent RT-PCR reactions. The simplified process can purify viral RNA from multiple samples within 20 min using a simple manual method or an automated high-throughput approach. By identifying two different regions (ORFlab and N gene) of viral RNA, a 10-copy sensitivity and a strong linear correlation between 10 and 105 copies of SARS-CoV-2 pseudovirus particles are achieved. Benefitting from the simplicity and excellent performances, this new extraction method can dramatically reduce the turn-around time and operational requirements in current molecular diagnosis of COVID-19, in particular for the early clinical diagnosis.",2020-02-27,"Zhao, Z.; Cui, H.; Song, W.; Ru, X.; Zhou, W.; Yu, X.",,,,True
2ffc83b88bc84615273e97d8109e5439ce4dce60,biorxiv,Adaptive Estimation for Epidemic Renewal and Phylogenetic Skyline Models,doi.org/10.1101/703751,,,See https://www.biorxiv.org/about-biorxiv,"Estimating temporal changes in a target population from phylogenetic or count data is an important problem in ecology and epidemiology. Reliable estimates can provide key insights into the climatic and biological drivers influencing the diversity or structure of that population and evidence hypotheses concerning its future growth or decline. In infectious disease applications, the individuals infected across an epidemic form the target population. The renewal model estimates the effective reproduction number, R, of the epidemic from counts of its observed cases. The skyline model infers the effective population size, N, underlying a phylogeny of sequences sampled from that epidemic. Practically, R measures ongoing epidemic growth while N informs on historical caseload. While both models solve distinct problems, the reliability of their estimates depends on p-dimensional piecewise-constant functions. If p is misspecified, the model might underfit significant changes or overfit noise and promote a spurious understanding of the epidemic, which might misguide intervention policies or misinform forecasts. Surprisingly, no transparent yet principled approach for optimising p exists. Usually, p is heuristically set, or obscurely controlled via complex algorithms. We present a computable and interpretable p-selection method based on the minimum description length (MDL) formalism of information theory. Unlike many standard model selection techniques, MDL accounts for the additional statistical complexity induced by how parameters interact. As a result, our method optimises p so that R and N estimates properly adapt to the available data. It also outperforms comparable Akaike and Bayesian information criteria on several classification problems. Our approach requires some knowledge of the parameter space and exposes the similarities between renewal and skyline models.",2020-02-27,"Parag, K. V.; Donnelly, C. A.",,,,True
0a32446730827ad8152c6a61e4738e4e0b231412,biorxiv,Artesunate interacts with Vitamin D receptor to reverse mouse model of sepsis-induced immunosuppression via enhancing autophagy,doi.org/10.1101/2020.02.26.966143,,,See https://www.biorxiv.org/about-biorxiv,"Background and PurposeImmunosuppression is the predominant cause of mortality for sepsis due to failure to eradicate invading pathogens. Unfortunately, no effective and specific drugs capable of reversing immunosuppression are available for clinical use. Increasing evidence implicates vitamin D receptor (VDR) involved in sepsis-induced immunosuppression. Herein, artesunate (AS) was discovered to reverse sepsis-induced immunosuppression and its molecular mechanism is investigated.  Experimental ApproachEffect of artesunate on sepsis-induced immunosuppression was investigated in mice and in vitro. VDR was predicted to be an interacted candidate of AS by bioinformatics predict, then identified using PCR and immunoblotting. VDR, ATG16L1 and NF-{kappa}B p65 were modified to investigate the alteration of ASs effect on pro-inflammatory cytokines release, bacteria clearance and autophagy activities in sepsis-induced immunosuppression.  Key ResultsAS significantly reduced the mortality of cecal ligation and puncture (CLP)-induced sepsis immunosuppression mice challenged with Pseudomonas Aeruginosa, and enhanced proinflammatory cytokines release and bacterial clearance to reverse sepsis-induced immunosuppression in vivo and in vitro. Mechanically, AS interacted with VDR thereby inhibited the nuclear translocation of VDR, then influencing ATG16L1 transcription and subsequent autophagy activity. In addition, AS inhibited physical interaction between VDR and NF-{kappa}B p65 in LPS tolerance macrophages, then promoted nuclear translocation of NF-{kappa}B p65, which activated the transcription of NF-{kappa}B p65 target genes such as pro-inflammatory cytokines.  Conclusion and ImplicationsOur findings provide an evidence that AS interacted with VDR to reverse sepsis-induced immunosuppression in an autophagy and NF-{kappa}B dependent way, highlighting a novel approach for sepsis treatment and drug repurposing of AS in the future.",2020-02-27,"Shang, S.; Wu, J.; Li, X.; Liu, X.; Li, P.; Zheng, C.; Wang, Y.; Liu, S.; Zheng, J.; Zhou, H.",,,,True
86b6b0c1b2777541feb83116bcb7a5cb12a52310,biorxiv,Comparative analysis of primer-probe sets for the laboratory confirmation of SARS-CoV-2,doi.org/10.1101/2020.02.25.964775,,,See https://www.biorxiv.org/about-biorxiv,"Coronavirus disease 2019 (COVID-19) is newly emerging human infectious diseases, which is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, also previously known as 2019-nCoV). Within two months of the outbreak, more than 80,000 cases of COVID-19 have been confirmed worldwide. Since the human to human transmission occurred easily and the human infection is rapidly increasing, the sensitive and early diagnosis is essential to prevent the global outbreak. Recently, World Health Organization (WHO) announced various primer and probe sets for SARS-CoV-2 previously developed in China, Germany, Hong Kong, Japan, Thailand, and USA. In this study, we compared the ability to detect SARS-CoV-2 RNA among the seven primer-probe sets for N gene and the three primer-probe sets for Orf1 gene. The result of the comparative analysis represented that the  2019-nCoV_N2, N3 of USA and the  ORF1ab of China are the most sensitive primer-probe sets for N and Orf1 genes, respectively. Therefore, the appropriate combination from ORF1ab (China), 2019-nCoV_N2, N3 (USA), and NIID_2019-nCOV_N (Japan) sets should be selected for the sensitive and reliable laboratory confirmation of SARS-CoV-2.",2020-02-27,"Jung, Y. J.; Park, G.-S.; Moon, J. H.; Ku, K.; Beak, S.-H.; Kim, S.; Park, E. C.; Park, D.; Lee, J.-H.; Byeon, C. W.; Lee, J. J.; Maeng, J.-s.; Kim, S. J.; Kim, S. I.; Kim, B.-T.; Lee, M. J.; Kim, H. G.",,,,True
949feecec7c10e71532e860f7f1230bd696e8234,biorxiv,Epitope-based peptide vaccines predicted against novel coronavirus disease caused by SARS-CoV-2,doi.org/10.1101/2020.02.25.965434,,,See https://www.biorxiv.org/about-biorxiv,"The outbreak of the 2019 novel coronavirus (SARS-CoV-2) has infected thousands of people with a large number of deaths across 26 countries. The sudden appearance of the virus leads to the limited existing therapies for SARS-CoV-2. Therefore, vaccines and antiviral medicines are in desperate need. This study took immune-informatics approaches to identify B- and T-cell epitopes for surface glycoprotein (S) of SARS-CoV-2, followed by estimating their antigenicity and interactions with the human leukocyte antigen (HLA) alleles. We identified four B cell epitopes, two MHC class-I and nine MHC class-II binding T-cell epitopes, which showed highly antigenic features. Allergenicity, toxicity and physiochemical properties analysis confirmed the specificity and selectivity of epitopes. The stability and safety of epitopes were confirmed by digestion analysis. No mutations were observed in all the selected B- and T-cell epitopes across all isolates from different locations worldwide. Epitopes were thus identified and some of them can be potential candidates for vaccine development.",2020-02-27,"Li, L.; Sun, T.; He, Y.; Li, W.; Fan, Y.; Zhang, J.",,,,True
c8b6f2752a842dd9eb9c50a82112748ef10ba259,biorxiv,Increasing Host Cellular Receptor--Angiotensin-Converting Enzyme 2 (ACE2) Expression by Coronavirus may Facilitate 2019-nCoV Infection,doi.org/10.1101/2020.02.24.963348,,,See https://www.biorxiv.org/about-biorxiv,"The ongoing outbreak of a new coronavirus (2019-nCoV) causes an epidemic of acute respiratory syndrome in humans. 2019-nCoV rapidly spread to national regions and multiple other countries, thus, pose a serious threat to public health. Recent studies show that spike (S) proteins of 2019-nCoV and SARS-CoV may use the same host cell receptor called angiotensin-converting enzyme 2 (ACE2) for entering into host cells. The affinity between ACE2 and 2019-nCoV S is much higher than ACE2 binding to SARS-CoV S protein, explaining that why 2019-nCoV seems to be more readily transmitted from the human to human. Here, we reported that ACE2 can be significantly upregulated after infection of various viruses including SARS-CoV and MERS-CoV. Basing on findings here, we propose that coronavirus infection can positively induce its cellular entry receptor to accelerate their replication and spread, thus drugs targeting ACE2 expression may be prepared for the future emerging infectious diseases caused by this cluster of viruses.",2020-02-27,"Wang, P.-H.",,,,True
eb7fc5004191e8fce0d6e4ff98de6865872e665f,biorxiv,Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2,doi.org/10.1101/2020.02.22.951178,,,See https://www.biorxiv.org/about-biorxiv,"Coronavirus disease 2019 (COVID-19) is a new emerging human infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, also previously known as 2019-nCoV), originated in Wuhan seafood and animal market, China. Since December 2019, more than 69,000 cases of COVID-19 have been confirmed in China and quickly spreads to other counties. Currently, researchers put their best efforts to identify effective drugs for COVID-19. The neutralizing antibody, which binds to viral capsid in a manner that inhibits cellular entry of virus and uncoating of the genome, is the specific defense against viral invaders. In this study, we investigate to identify neutralizing antibodies that can bind to SARS-CoV-2 Sipke (S) protein and interfere with the interaction between viral S protein and a host receptor by bioinformatic methods. The sequence analysis of S protein showed two major differences in the RBD region of the SARS-CoV-2 S protein compared to SARS-CoV and SARS-CoV related bat viruses (btSARS-CoV). The insertion regions were close to interacting residues with the human ACE2 receptor. Epitope analysis of neutralizing antibodies revealed that SARS-CoV neutralizing antibodies used conformational epitopes, whereas MERS-CoV neutralizing antibodies used a common linear epitope region, which contributes to form the {beta}-sheet structure in MERS-CoV S protein and deleted in SARS-CoV-2 S protein. To identify effective neutralizing antibodies for SARS-CoV-2, the binding affinities of neutralizing antibodies with SARS-CoV-2 S protein were predicted and compared by antibody-antigen docking simulation. The result showed that CR3022 neutralizing antibody from human may have higher binding affinity with SARS-CoV-2 S protein than SARS-CoV S protein. We also found that F26G19 and D12 mouse antibodies could bind to SARS-CoV S protein with high affinity. Our findings provide crucial clues towards the development of antigen diagnosis, therapeutic antibody, and the vaccine against SARS-CoV-2.",2020-02-27,"Park, T.; Lee, S.-Y.; Kim, S.; Kim, M. J.; Kim, H. G.; Jun, S.; Kim, S. I.; Kim, B. T.; Park, E. C.; Park, D.",,,,True
ae66f22f886d3b019934ae237c11a5fb53dbefb2,biorxiv,Prediction of receptorome for human-infecting virome,doi.org/10.1101/2020.02.27.967885,,,See https://www.biorxiv.org/about-biorxiv,"The virus receptor is key for viral infection of host cells. Identification of the virus receptor is still challenging at present. Our previous study has shown that human virus receptor proteins have some unique features including high level of N-glycosylation, high number of interaction partners and high expressions. Here, we built a random-forest model to identify human virus receptorome from human cell membrane proteins with accepted accuracy based on combination of unique features of human virus receptors and protein sequences. A total of 729 human cell membrane proteins were predicted to constitute the receptorome for the human-infecting virome. Combination of the random-forest model with protein-protein interactions between human and viruses predicted in previous studies further predicted receptors for 693 human-infecting viruses, such as the Enterovirus, Norovirus and West Nile virus. Finally, we predicted the candidate alternative receptors for the 2019-nCoV. The study would greatly facilitate identification of receptors for human-infecting virome.",2020-02-28,"Zhang, Z.; Ye, S.; Wu, A.; Jiang, T.; Peng, Y.",,,,True
52a01a1116ed6a1297fb3dd63412d8d7d221a8e9,biorxiv,The Pathogenicity of SARS-CoV-2 in hACE2 Transgenic Mice,doi.org/10.1101/2020.02.07.939389,,,See https://www.biorxiv.org/about-biorxiv,"Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the Corona Virus Disease 2019 (COVID-19) cases in China has become a public health emergency of international concern (PHEIC). Based on angiotensin converting enzyme 2 (ACE2) as cell entry receptor of SARS-CoV, we used the hACE2 transgenic mice infected with SARS-CoV-2 to study the pathogenicity of the virus. Weight loss and virus replication in lung were observed in hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of significant lymphocytes and monocytes in alveolar interstitium, and accumulation of macrophages in alveolar cavities. Viral antigens were observed in the bronchial epithelial cells, alveolar macrophages and alveolar epithelia. The phenomenon was not found in wild type mice with SARS-CoV-2 infection. The pathogenicity of SARS-CoV-2 in hACE2 mice was clarified and the Kochs postulates were fulfilled as well, and the mouse model may facilitate the development of therapeutics and vaccines against SARS-CoV-2.",2020-02-28,"Bao, L.; Deng, W.; Huang, B.; Gao, H.; Liu, J.; Ren, L.; Wei, Q.; Yu, P.; Xu, Y.; Qi, F.; Qu, Y.; Li, F.; Lv, Q.; Wang, W.; Xue, J.; Gong, S.; Liu, M.; Wang, G.; Wang, S.; Song, Z.; Zhao, L.; Liu, P.; Zhao, L.; Ye, F.; Wang, H.; Zhou, W.; Zhu, N.; Zhen, W.; Yu, H.; Zhang, X.; Guo, L.; Chen, L.; Wang, C.; Wang, Y.; Wang, X.; Xiao, Y.; Sun, Q.; Liu, H.; Zhu, F.; Ma, C.; Yan, L.; Yang, M.; Han, J.; Xu, W.; Tan, W.; Peng, X.; Jin, Q.; Wu, G.; Qin, C.",,,,False
210912792a1547a437a4640fadc339c08982bb14,biorxiv,"An ultrasensitive, rapid, and portable coronavirus SARS-CoV-2 sequence detection method based on CRISPR-Cas12",doi.org/10.1101/2020.02.29.971127,,,See https://www.biorxiv.org/about-biorxiv,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has received global attention due to the recent outbreak in China. In this work, we report a CRISPR-Cas12 based diagnostic tool to detect synthetic SARS-CoV-2 RNA sequences in a proof-of-principle evaluation. The test proved to be sensitive, rapid, and potentially portable. These key traits of the CRISPR method are critical for virus detection in regions that lack resources to use the currently available methods.",2020-03-02,"Curti, L.; Pereyra-Bonnet, F.; Gimenez, C.",,,,False
6d0127f985edbe088bc279865bef25a31f54a066,biorxiv,Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13,doi.org/10.1101/2020.02.27.969006,,,See https://www.biorxiv.org/about-biorxiv,"The novel coronavirus SARS-CoV-2 (2019-nCoV) is a member of the family coronaviridae and contains a single-stranded RNA genome with positive-polarity. To reveal the evolution mechanism of SARS-CoV-2 genome, we performed comprehensive genomic analysis with newly sequenced SARS-CoV-2 strains and 20 closely related coronavirus strains. Among 98 nucleotide mutations at 93 sites of the genome among different SARS-CoV-2 strains, 58 of them caused amino acid change, indicating a result of neutral evolution. However, the ratio of nucleotide substitutions to amino acid substitutions of spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-SARSr-CoV RaTG13 was extensively higher than those from comparisons between other coronaviruses (range 1.29 - 4.81). The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection. Moreover, their nucleotide substitutions are enriched with T:C transition, which is consistent with the mutation signature caused by deactivity of RNA 3-to-5 exoribonuclease (ExoN). The codon usage was similar between SARS-CoV-2 and other strains in beta-coronavirus lineage B, suggesting it had small impact on the mutation pattern. In comparison of SARS-CoV-2 WIV04 with Bat-SARSr-CoV RaTG13, the ratios of non-synonymous to synonymous substitution rates (dN/dS) was the lowest among all performed comparisons, reconfirming the evolution of SARS-CoV-2 under stringent selective pressure. Moreover, some sites of spike protein might be subjected to positive selection. Therefore, our results will help understanding the evolutionary mechanisms contribute to viral pathogenicity and its adaptation with hosts.",2020-03-02,"Lv, L.; Li, G.; Chen, J.; Liang, X.; Li, Y.",,,,True
35604e3a5d38d6794543372e4dd9ccf1d8d9cd2a,biorxiv,CRISPR-based surveillance for COVID-19 using genomically-comprehensive machine learning design,doi.org/10.1101/2020.02.26.967026,,,See https://www.biorxiv.org/about-biorxiv,"The emergence and outbreak of SARS-CoV-2, the causative agent of COVID-19, has rapidly become a global concern and has highlighted the need for fast, sensitive, and specific tools to surveil circulating viruses. Here we provide assay designs and experimental resources, for use with CRISPR-based nucleic acid detection, that could be valuable for ongoing surveillance. We provide assay designs for detection of 67 viral species and subspecies, including: SARS-CoV-2, phylogenetically-related viruses, and viruses with similar clinical presentation. The designs are outputs of algorithms that we are developing for rapidly designing nucleic acid detection assays that are comprehensive across genomic diversity and predicted to be highly sensitive and specific. Of our design set, we experimentally screened 4 SARS-CoV-2 designs with a CRISPR-Cas13 detection system and then extensively tested the highest-performing SARS-CoV-2 assay. We demonstrate the sensitivity and speed of this assay using synthetic targets with fluorescent and lateral flow detection. Moreover, our provided protocol can be extended for testing the other 66 provided designs. Assay designs are available at https://adapt.sabetilab.org/.",2020-03-02,"Metsky, H. C.; Freije, C. A.; Kosoko-Thoroddsen, T.-S. F.; Sabeti, P. C.; Myhrvold, C.",,,,True
74b00f19c3af87d1081644f02490ba250f57b7ca,biorxiv,Design of multi epitope-based peptide vaccine against E protein of human COVID-19: An immunoinformatics approach,doi.org/10.1101/2020.02.04.934232,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundNew endemic disease has been spread across Wuhan City, China on December 2019. Within few weeks, the World Health Organization (WHO) announced a novel coronavirus designated as coronavirus disease 2019 (COVID-19). In late January 2020, WHO declared the outbreak of a ""public-health emergency of international concern"" due to the rapid and increasing spread of the disease worldwide. Currently, there is no vaccine or approved treatment for this emerging infection; thus the objective of this study is to design a multi epitope peptide vaccine against COVID-19 using immunoinformatics approach.  MethodSeveral techniques facilitating the combination of immunoinformatics approach and comparative genomic approach were used in order to determine the potential peptides for designing the T cell epitopes-based peptide vaccine using the envelope protein of 2019-nCoV as a target.  ResultsExtensive mutations, insertion and deletion were discovered with comparative sequencing in COVID-19 strain. Additionally, ten peptides binding to MHC class I and MHC class II were found to be promising candidates for vaccine design with adequate world population coverage of 88.5% and 99.99%, respectively.  ConclusionT cell epitopes-based peptide vaccine was designed for COVID-19 using envelope protein as an immunogenic target. Nevertheless, the proposed vaccine is rapidly needed to be validated clinically in order to ensure its safety, immunogenic profile and to help on stopping this epidemic before it leads to devastating global outbreaks.",2020-03-02,"Abdelmageed, M. I.; Abdelmoneim, A. H.; Mustafa, M. I.; Elfadol, N. M.; Murshed, N. S.; Shantier, S. W.; Makhawi, A. M.",,,,True
665da35efd7c51c6975857ce12acf7dde04fb510,biorxiv,Designing of a next generation multiepitope based vaccine (MEV) against SARS-COV-2: Immunoinformatics and in silico approaches,doi.org/10.1101/2020.02.28.970343,,,See https://www.biorxiv.org/about-biorxiv,"Coronavirus disease 2019 (COVID-19) associated pneumonia caused by severe acute respiratory coronavirus 2 (SARS-COV-2) was first reported in Wuhan, China in December 2019. Till date, no vaccine or completely effective drug is available for the cure of COVID-19. Therefore, an effective vaccine against SARS-COV-2 is needed to be design. This study was conducted to design an effective multi-epitope vaccine (MEV) against SARS-COV-2. Seven antigenic proteins were taken as a target and epitopes (B cell, IFN-{gamma} and T cell) were predicted. Highly antigenic and overlapping epitopes were shortlisted. Selected T cell epitopes indicated significant interactions with the HLA-binding alleles and 99.29% coverage of the worlds population. Finally, 505 amino acids long MEV was designed by connecting sixteen MHC class I and twelve MHC class II epitopes with suitable linkers and adjuvant. Linkers and adjuvant were added to enhance the immunogenicity response of the vaccine. The allergenicity, physiochemical properties, antigenicity and structural details of MEV were analyzed in order to ensure safety and immunogenicity. MEV construct was non-allergenic and antigenic. Molecular docking demonstrated a stable and strong binding affinity of MEV with TLR3 and TLR8. Codon optimization and in silico cloning ensured increased expression in the Escherichia coli K-12 system. However, to ensure its safety and immunogenic profile, the proposed vaccine needs to be experimentally validated.",2020-03-02,"Tahir ul Qamar, M.; Rehman, A.; Ashfaq, U. A.; Awan, M. Q.; Fatima, I.; Shahid, F.; Chen, L.-L.",,,,False
a891d059692c951d1fb0fb36914fe451f973684a,biorxiv,Kallikrein 13: a new player in coronaviral infections.,doi.org/10.1101/2020.03.01.971499,,,See https://www.biorxiv.org/about-biorxiv,"Human coronavirus HKU1 (HCoV-HKU1) is associated with respiratory disease and is prevalent worldwide, but in vitro model for virus replication is lacking. Interaction between the coronaviral spike (S) protein and its receptor is the major determinant of virus tissue and host specificity, but virus entry is a complex process requiring a concerted action of multiple cellular elements. Here, we show that KLK13 is required for the infection of the human respiratory epithelium and is sufficient to mediate the entry of HCoV-HKU1 to non-permissive RD cells. We also demonstrated HCoV-HKU1 S protein cleavage by KLK13 in the S1/S2 region, proving that KLK13 is the priming enzyme for this virus. Summarizing, we show for the first time that protease distribution and specificity predetermines the tissue and cell specificity of the virus and may also regulate interspecies transmission. It is also of importance that presented data may be relevant for the emerging coronaviruses, including SARS-CoV-2 and may help to understand the differences in their zoonotic potential.",2020-03-02,"Milewska, A.; Falkowski, K.; Kalinska, M.; Bielecka, E.; Naskalska, A.; Mak, P.; Lesner, A.; Ochman, M.; Urlik, M.; Potempa, J.; Kantyka, T.; Pyrc, K.",,,,True
3d3d536de77577af8dbf3067883990ff6d17faa8,biorxiv,Molecular Dynamics Simulations Indicate the COVID-19 Mpro Is Not a Viable Target for Small-Molecule Inhibitors Design,doi.org/10.1101/2020.02.27.968008,,,See https://www.biorxiv.org/about-biorxiv,"The novel coronavirus whose outbreak took place in December 2019 continues to spread at a rapid rate worldwide. In the absence of an effective vaccine, inhibitor repurposing or de novo design may offer a longer-term strategy to combat this and future infections due to similar viruses. Here, we report on detailed molecular dynamics simulations of the main protease (Mpro). We compared and contrasted the Mpro for COVID-19 with a highly similar SARS protein. In spite of a high level of sequence similarity, the active sites in both proteins show major differences in both shape and size indicating that repurposing SARS drugs for COVID-19 may be futile. Furthermore, analysis of the pockets time-dependence indicates its flexibility and plasticity, which dashes hopes for rapid and reliable drug design. Conversely, structural stability of the protein with respect to flexible loop mutations indicates that the virus mutability will pose a further challenge to the rational design of small-molecule inhibitors.",2020-03-02,"Bzowka, M.; Mitusinska, K.; Raczynska, A.; Samol, A.; Tuszynski, J. A.; Gora, A.",,,,True
2ea102f58147dab02e4dea90eb90dbc67149f678,biorxiv,"Mutations, Recombination and Insertion in the Evolution of 2019-nCoV",doi.org/10.1101/2020.02.29.971101,,,See https://www.biorxiv.org/about-biorxiv,"BackgroundThe 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) has spread more rapidly than any other betacoronavirus including SARS-CoV and MERS-CoV. However, the mechanisms responsible for infection and molecular evolution of this virus remained unclear.  MethodsWe collected and analyzed 120 genomic sequences of 2019-nCoV including 11 novel genomes from patients in China. Through comprehensive analysis of the available genome sequences of 2019-nCoV strains, we have tracked multiple inheritable SNPs and determined the evolution of 2019-nCoV relative to other coronaviruses.  ResultsSystematic analysis of 120 genomic sequences of 2019-nCoV revealed co-circulation of two genetic subgroups with distinct SNPs markers, which can be used to trace the 2019-nCoV spreading pathways to different regions and countries. Although 2019-nCoV, human and bat SARS-CoV share high homologous in overall genome structures, they evolved into two distinct groups with different receptor entry specificities through potential recombination in the receptor binding regions. In addition, 2019-nCoV has a unique four amino acid insertion between S1 and S2 domains of the spike protein, which created a potential furin or TMPRSS2 cleavage site.  ConclusionsOur studies provided comprehensive insights into the evolution and spread of the 2019-nCoV. Our results provided evidence suggesting that 2019-nCoV may increase its infectivity through the receptor binding domain recombination and a cleavage site insertion.  One Sentence SummaryNovel 2019-nCoV sequences revealed the evolution and specificity of betacoronavirus with possible mechanisms of enhanced infectivity.",2020-03-02,"Wu, A.; Niu, P.; Wang, L.; Zhou, H.; Zhao, X.; Wang, W.; Wang, J.; Ji, C.; Ding, X.; Wang, X.; Lu, R.; Gold, S.; Aliyari, S.; Zhang, S.; Vikram, E.; Zou, A.; Lenh, E.; Chen, J.; Ye, F.; Han, N.; Peng, Y.; Guo, H.; Wu, G.; Jiang, T.; Tan, W.; Cheng, G.",,,,True
11875dfda6cd04d5032611edf0e340582ceb620f,biorxiv,Predictions for the binding domain and potential new drug targets of 2019-nCoV,doi.org/10.1101/2020.02.26.961938,,,See https://www.biorxiv.org/about-biorxiv,"An outbreak of new SARS-like viral in Wuhan, China has been named 2019-nCoV. The current state of the epidemic is increasingly serious, and there has been the urgent necessity to develop an effective new drug. In previous studies, it was found that the conformation change in CTD1 was the region where SARS-CoV bound to human ACE2. Although there are mutations of the 2019-nCoV, the binding energy of ACE2 remains high. The surface glycoprotein of 2019-nCoV was coincident with the CTD1 region of the S-protein by comparing the I-TASSER prediction model with the actual SARS model, which suggests that 2019-nCoV may bind to the ACE2 receptor through conformational changes. Furthermore, site prediction on the surface glycoprotein of 2019-nCoV suggests some core amino acid area may be a novel drug target against 2019-nCoV.",2020-03-02,"Zeng, Z.; Zhi, L.; Du, H.",,,,True
dbefc8ad2a3de5d1696b7e604de8bce1da2ea8cd,biorxiv,Screening of FDA-approved drugs using a MERS-CoV clinical isolate from South Korea identifies potential therapeutic options for COVID-19,doi.org/10.1101/2020.02.25.965582,,,See https://www.biorxiv.org/about-biorxiv,"In 2015, the Middle East respiratory syndrome coronavirus (MERS-CoV) reached the Republic of Korea, resulting from nosocomial transmission, and was the largest epidemic outside of the Arabian Peninsula. To date, despite various strategies to identify CoV interventions, there are only limited therapeutic options available. To address these unmet medical needs, we used a South Korean MERS-CoV clinical isolate and screened 5,406 compounds, including US Food and Drug Administration (FDA)-approved drugs and bioactive molecules, confirmed 221 hits by dose-response curve analysis in the primary assay, and selected 54 hits with a therapeutic index (TI) greater than 6. Time-of-addition studies with 12 FDA-approved drugs demonstrated that eight and four therapeutics act on the early- and late stages of the viral life cycle, respectively. Among the early acting drugs, three therapeutics with a TI greater than 100 were cardiotonic agents. Together, our results identify potential therapeutic options for treatment of MERS-CoV infections and could provide a basis for a wider range of coronaviruses, including the currently emerging coronavirus disease 2019 (COVID-19) outbreak.",2020-03-02,"Ko, M.; Chang, S. Y.; Byun, S. Y.; Choi, I.; d'Alexandry d'Orengiani, A. L. P. H.; Shum, D.; Min, J.-Y.; Windisch, M. P.",,,,True
1b9fed2824e97db8cb35912549dd2e9cde7b6c18,biorxiv,Strategies for vaccine design for corona virus using Immunoinformatics techniques,doi.org/10.1101/2020.02.27.967422,,,See https://www.biorxiv.org/about-biorxiv,"The cutting-edge technology vaccinomics is the combination of two topics immunogenetics and immunogenomics with the knowledge of systems biology and immune profiling for designing vaccine against infectious disease. In our present study, an epitope-based peptide vaccine against nonstructural protein 4 of beta coronavirus, using a combination of B cell and T cell epitope predictions, followed by molecular docking methods are performed. Here, protein sequences of homologous nonstructural protein 4 of beta coronavirus are collected and conserved regions present in them are investigated via phylogenetic study to determine the most immunogenic part of protein. From the identified region of the target protein, the peptide sequence IRNTTNPSAR from the region ranging from 38-47 and the sequence PTDTYTSVYLGKFRG from the positions of 76-90 are considered as the most potential B cell and T cell epitopes respectively. Furthermore, this predicted T cell epitopes PTDTYTSVY and PTDTYTSVYLGKFRG interacted with MHC allelic proteins HLA-A*01:01 and HLA-DRB5*01:01 respectively with the low IC50 values. These epitopes are perfectly fitted into the epitope binding grooves of alpha helix of MHC I molecule and MHC II molecule with binding energy scores -725.0 Kcal/mole and -786.0 Kcal/mole respectively, showing stability in MHC molecules binding. This MHC restricted epitope PTDTYTSVY also showed a good conservancy of 50.16% in world population coverage. This MHC I HLA-A*01:01 allele is present among 58.87% of Chinese population also. Therefore, the epitopes IRNTTNPSAR and PTDTYTSVYLGKFRG may be considered as potential peptides for peptide-based vaccine for coronavirus after further experimental study.",2020-03-02,"Basu, A.; Sarkar, A.; Maulik, U.",,,,True
07e833d0917cace550853f72923856d0fe1a7120,biorxiv,The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding.,doi.org/10.1101/2020.02.29.971093,,,See https://www.biorxiv.org/about-biorxiv,"Many pathogens take advantage of the dependence of the host on the interaction of hundreds of extracellular proteins with the glycosaminoglycans heparan sulfate to regulate homeostasis and use heparan sulfate as a means to adhere and gain access to cells. Moreover, mucosal epithelia such as that of the respiratory tract are protected by a layer of mucin polysaccharides, which are usually sulfated. Consequently, the polydisperse, natural products of heparan sulfate and the allied polysaccharide, heparin have been found to be involved and prevent infection by a range of viruses including S-associated coronavirus strain HSR1. Here we use surface plasmon resonance and circular dichroism to measure the interaction between the SARS-CoV-2 Spike S1 protein receptor binding domain (SARS-CoV-2 S1 RBD) and heparin. The data demonstrate an interaction between the recombinant surface receptor binding domain and the polysaccharide. This has implications for the rapid development of a first-line therapeutic by repurposing heparin and for next-generation, tailor-made, GAG-based antivirals.",2020-03-02,"Mycroft-West, C. J.; Su, D.; Elli, S.; Guimond, S. E.; Miller, G. J.; Turnbull, J. E.; Yates, E. A.; Guerrini, M.; Fernig, D. G.; Andrade de Lima, M.; Skidmore, M. A.",,,,True
92c020779e68e82d9a5f5898435e618caa63a099,biorxiv,"TWIRLS, an automated topic-wise inference method based on massive literature, suggests a possible mechanism via ACE2 for the pathological changes in the human host after coronavirus infection",doi.org/10.1101/2020.02.27.967588,,,See https://www.biorxiv.org/about-biorxiv,"Faced with the current large-scale public health emergency, collecting, sorting, and analyzing biomedical information related to the ""coronavirus"" should be done as quickly as possible to gain a global perspective, which is a basic requirement for strengthening epidemic control capacity. However, for human researchers studying the viruses and the hosts, the vast amount of information available cannot be processed effectively and in a timely manner, particularly when the scientific understanding may be limited, which can further lower the information processing efficiency. We present TWIRLS, a method that can automatically acquire, organize, and classify information. Additionally, independent functional data sources can be added to build an inference system using a machine-based approach, which can provide relevant knowledge to help human researchers quickly establish subject cognition and to make more effective decisions. TWIRLS can automatically analyze more than three million words in more than 14,000 literature articles in only 4 hours. Combining with generalized gene interaction databases creates a data interface that can help researchers to further analyze the information. Using the TWIRLS system, we found that an important regulatory factor angiotensin-converting enzyme 2 (ACE2) may be involved in the host pathological changes on binding to the coronavirus after infection. After triggering functional changes in ACE2/AT2R, an imbalance in the steady-state cytokine regulatory axis involving the Renin-Angiotensin System and IP-10 leads to a cytokine storm.",2020-03-02,"Ji, X.; Zhang, C.; Zhai, Y.; Zhang, Z.; Zhang, C.; Xue, Y.; Tan, G.; Niu, G.",,,,True
3d498994d143a4ed7cc381700a19f2790d46bb36,biorxiv,Vorpal: A Novel RNA Virus Feature-Extraction Algorithm Demonstrated Through Interpretable Genotype-to-Phenotype Linear Models,doi.org/10.1101/2020.02.28.969782,,,See https://www.biorxiv.org/about-biorxiv,"In the analysis of genomic sequence data, so-called ""alignment free"" approaches are often selected for their relative speed compared to alignment-based approaches, especially in the application of distance comparisons and taxonomic classification1,2,3,4. These methods are typically reliant on excising K-length substrings of the input sequence, called K-mers5. In the context of machine learning, K-mer based feature vectors have been used in applications ranging from amplicon sequencing classification to predictive modeling for antimicrobial resistance genes6,7,8. This can be seen as an analogy of the ""bag-of-words"" model successfully employed in natural language processing and computer vision for document and image classification9,10. Feature extraction techniques from natural language processing have previously been analogized to genomics data11; however, the ""bag-of-words"" approach is brittle in the RNA virus space due to the high intersequence variance and the exact matching requirement of K-mers. To reconcile the simplicity of ""bag-of-words"" methods with the complications presented by the intrinsic variance of RNA virus space, a method to resolve the fragility of extracted K-mers in a way that faithfully reflects an underlying biological phenomenon was devised. Our algorithm, Vorpal, allows the construction of interpretable linear models with clustered, representative  degenerate K-mers as the input vector and, through regularization, sparse predictors of binary phenotypes as the output. Here, we demonstrate the utility of Vorpal by identifying nucleotide-level genomic motif predictors for binary phenotypes in three separate RNA virus clades; human pathogen vs. non-human pathogen in Orthocoronavirinae, hemorrhagic fever causing vs. non-hemorrhagic fever causing in Ebolavirus, and human-host vs. non-human host in Influenza A. The capacity of this approach for in silico identification of hypotheses which can be validated by direct experimentation, as well as identification of genomic targets for preemptive biosurveillance of emerging viruses, is discussed. The code is available for download at https://github.com/mriglobal/vorpal.",2020-03-02,"Davis, P.; Bagnoli, J.; Yarmosh, D.; Shteyman, A.; Presser, L.; Altmann, S.; Bradrick, S.; Russell, J. A.",,,,True
c15f8c23eedbedf8d48bbc88b8225ae9c9d234bf,biorxiv,Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2,doi.org/10.1101/2020.03.02.968388,,,See https://www.biorxiv.org/about-biorxiv,"Severe Acute Respiratory Syndrome Coronavirus 2 is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS- and MERS-CoVs the detailed information about SARS-CoV-2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies and antivirals. We applied high-throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS-CoV-2 proteins and structures. Here we report the high-resolution crystal structure of endoribonuclease Nsp15/NendoU from SARS-CoV-2 - a virus causing current world-wide epidemics. We compare this structure with previously reported models of Nsp15 from SARS and MERS coronaviruses.",2020-03-03,"Kim, Y.; Jedrzejczak, R.; Maltseva, N. I.; Endres, M.; Godzik, A.; Michalska, K.; Joachimiak, A.",,,,True
bad4192bbc6d41c066bc947eaeeafc53024c98be,biorxiv,Evidence for RNA editing in the transcriptome of 2019 Novel Coronavirus,doi.org/10.1101/2020.03.02.973255,,,See https://www.biorxiv.org/about-biorxiv,"The 2019-nCoV outbreak has become a global health risk. Editing by host deaminases is an innate restriction process to counter viruses, and it is not yet known whether it operates against coronaviruses. Here we analyze RNA sequences from bronchoalveolar lavage fluids derived from two Wuhan patients. We identify nucleotide changes that may be signatures of RNA editing: Adenosine-to-Inosine changes from ADAR deaminases and Cytosine-to-Uracil changes from APOBEC ones. A mutational analysis of genomes from different strains of human-hosted Coronaviridae reveals patterns similar to the RNA editing pattern observed in the 2019-nCoV transcriptomes. Our results suggest that both APOBECs and ADARs are involved in Coronavirus genome editing, a process that may shape the fate of both virus and patient.",2020-03-03,"Di Giorgio, S.; Martignano, F.; Torcia, M. G.; Mattiuz, G.; Conticello, S. G.",,,,True
6bfd857ccf24e8a07e5ea9241482743ac45fcd36,biorxiv,Multi-epitope vaccine design using an immunoinformatics approach for 2019 novel coronavirus in China (SARS-CoV-2),doi.org/10.1101/2020.03.03.962332,,,See https://www.biorxiv.org/about-biorxiv,"A new coronavirus SARS-CoV-2, recently discovered in Wuhan, China, has caused over 74000 infection cases and 2000 deaths. Due to the rapidly growing cases and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. In the present study, we performed an in silico approach based on the available virus genome to identify the antigenic B-cell epitopes and human-leukocyte-antigen (HLA) restricted T-cell epitopes. A total of 61 B-cell epitopes were initially identified, 19 of which with higher potential immunogenicity were used for vaccine design. 499 T-cell epitopes were predicted that showed affinity with the 34 most popular HLA alleles in Chinese population. Based on these epitopes, 30 vaccine candidates were designed and inspected against safety risks, including potential toxicity, human homologous, pharmaceutical peptides and bioactive peptides. Majority of vaccine peptides contained both B-cell and T-cell epitopes, which may interact with the most prevalent HLA alleles accounting for ~99% of Chinese population. Docking analysis showed stable hydrogen bonds of epitopes with their corresponding HLA alleles. In conclusion, these putative antigenic peptides may elicit the resistance response to the viral infection. In vitro and in vivo experiments are required to validate the effectiveness of these peptide vaccine.",2020-03-03,"Feng, Y.; Qiu, M.; Zou, S.; Li, Y.; Luo, K.; Chen, R.; Sun, Y.; Wang, K.; Zhuang, X.; Zhang, S.; Chen, S.; Mo, F.",,,,False
1d2947d5c0addcbbcfa71d87ea074a8b6ff2a973,biorxiv,Speed and strength of an epidemic intervention,doi.org/10.1101/2020.03.02.974048,,,See https://www.biorxiv.org/about-biorxiv,"An epidemic can be characterized by its speed (i.e., the exponential growth rate r) and strength (i.e., the reproductive number [R]). Disease modelers have historically placed much more emphasis on strength, in part because the effectiveness of an intervention strategy is typically evaluated on this scale. Here, we develop a mathematical framework for this classic, strength-based paradigm and show that there is a corresponding speed-based paradigm which can provide complementary insights. In particular, we note that r = 0 is a threshold for disease spread, just like [R] = 1, and show that we can measure the speed and strength of an intervention on the same scale as the speed and strength of an epidemic, respectively. We argue that, just as the strength-based paradigm provides the clearest insight into certain questions, the speed-based paradigm provides the clearest view in other cases. As an example, we show that evaluating the prospects of ""test-and-treat"" interventions against the human immunodeficiency virus (HIV) can be done more clearly on the speed than strength scale, given uncertainty in the proportion of HIV spread that happens early in the course of infection. We suggest that disease modelers should avoid over-emphasizing the reproductive number at the expense of the exponential growth rate, but instead look at these as complementary measures.",2020-03-03,"Dushoff, J.; Park, S. W.",,,,True
7bdceb3b947ec934199d0c97fb9ec5a0e2bac776,biorxiv,Strong evolutionary convergence of receptor-binding protein spike between COVID-19 and SARS-related coronaviruses,doi.org/10.1101/2020.03.04.975995,,,See https://www.biorxiv.org/about-biorxiv,"Coronavirus Disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS)-related coronaviruses (e.g., 2019-nCoV and SARS-CoV) are phylogenetically distantly related, but both are capable of infecting human hosts via the same receptor, angiotensin-converting enzyme 2, and cause similar clinical and pathological features, suggesting their phenotypic convergence. Yet, the molecular basis that underlies their phenotypic convergence remains unknown. Here, we used a recently developed molecular phyloecological approach to examine the molecular basis leading to their phenotypic convergence. Our genome-level analyses show that the spike protein, which is responsible for receptor binding, has undergone significant Darwinian selection along the branches related to 2019-nCoV and SARS-CoV. Further examination shows an unusually high proportion of evolutionary convergent amino acid sites in the receptor binding domain (RBD) of the spike protein between COVID-19 and SARS-related CoV clades, leading to the phylogenetic uniting of their RBD protein sequences. In addition to the spike protein, we also find the evolutionary convergence of its partner protein, ORF3a, suggesting their possible co-evolutionary convergence. Our results demonstrate a strong adaptive evolutionary convergence between COVID-19 and SARS-related CoV, possibly facilitating their adaptation to similar or identical receptors. Finally, it should be noted that many observed bat SARS-like CoVs that have an evolutionary convergent RBD sequence with 2019-nCoV and SARS-CoV may be pre-adapted to human host receptor ACE2, and hence would be potential new coronavirus sources to infect humans in the future.",2020-03-04,"Wu, Y.",,,,True
2eac7de1c407d9eab13a6d538142cd21a814ee7b,biorxiv,Rapid metagenomic characterization of a case of imported COVID-19 in Cambodia,doi.org/10.1101/2020.03.02.968818,,,See https://www.biorxiv.org/about-biorxiv,"Rapid production and publication of pathogen genome sequences during emerging disease outbreaks provide crucial public health information. In resource-limited settings, especially near an outbreak epicenter, conventional deep sequencing or bioinformatics are often challenging. Here we successfully used metagenomic next generation sequencing on an iSeq100 Illumina platform paired with an open-source bioinformatics pipeline to quickly characterize Cambodias first case of COVID-2019.",2020-03-05,"Manning, J. E.; Bohl, J. A.; Lay, S.; Chea, S.; Ly, S.; Sengdoeurn, Y.; Heng, S.; Vuthy, C.; Kalantar, K.; Ahyong, V.; Tan, M.; Sheu, J.; Tato, C. M.; DeRisi, J.; Baril, L.; Dussart, P.; Duong, V.; Karlsson, E. A.",,,,True
0fa18c47543c3ce69a3c9e4d77958c4d3691b1ed,biorxiv,Significance of hydrophobic and charged sequence similarities in sodium-bile acid cotransporter and vitamin D-binding protein macrophage activating factor,doi.org/10.1101/2020.03.03.975524,,,See https://www.biorxiv.org/about-biorxiv,"Sodium-bile acid cotransporter, also denominated sodium-taurocholate cotransporting polypeptide (NTCP) is an integral membrane protein with multiple hydrophobic transmembrane domains. The third extracellular domain of NTCP presents a stretch of nine aminoacids (KGIVISLVL) that is characterized by pronounced hydrophobicity and serves as receptor for a protein, preS1, showing the hydrophobic epta-peptide sequence NPLGFFP. Vitamin D-binding protein macrophage activating factor (DBP-MAF) is a multifunctional protein that is characterized by two hydrophobic regions able to bind fatty acids and vitamin D, respectively. Here we demonstrate that NTCP and DBP-MAF show significant sequence similarities as far as hydrophobic stretches of aminoacids are concerned. Alignment of the sequence of seven aminoacids preceding the 157-KGIVISLVL-165 stretch of NTCP shows four aminoacids that are identical to those of the corresponding sequence of DBP-MAF, and two that are conserved substitutions. In addition, in the sequence of DBP-MAF that is aligned with the sequence YKGIVISLVL of NTCP, there are two contiguous negatively charged aminoacids (ED) and, in the preceding epta-peptide sequence, there are three negatively charged aminoacids (D-ED), whereas in the corresponding sequence of NTCP there are only two (D--D) that are not contiguous. This concentration of negatively charged aminoacids may be involved in binding of protein inserts characterized by high density of positively charges residues. The alternating hydrophobic and electrostatic interactions described in this paper may help elucidating the biological roles of these proteins as far as protein-protein interactions are concerned.",2020-03-05,"Zunaid, I. R.; Pacini, S.; Ruggiero, M.",,,,True
0624a12abfe85c8b5070850d912a2db4cd453236,biorxiv,TALC: Transcription-Aware Long Read Correction,doi.org/10.1101/2020.01.10.901728,,,See https://www.biorxiv.org/about-biorxiv,"MotivationLong-read sequencing technologies are invaluable for determining complex RNA transcript architectures but are error-prone. Numerous ""hybrid correction"" algorithms have been developed for genomic data that correct long reads by exploiting the accuracy and depth of short reads sequenced from the same sample. These algorithms are not suited for correcting more complex transcriptome sequencing data.  ResultsWe have created a novel algorithm called TALC (Transcription Aware Long Read Correction) which models changes in RNA expression and isoform representation in a weighted De-Bruijn graph to correct long reads from transcriptome studies. We show that transcription aware correction by TALC improves the accuracy of the whole spectrum of downstream RNA-seq applications and is thus necessary for transcriptome analyses that use long read technology.  Availability and ImplementationTALC is implemented in C++ and available at https://gitlab.igh.cnrs.fr/lbroseus/TALC.  Contactwilliam.ritchie@igh.cnrs.fr",2020-03-05,"Broseus, L.; Thomas, A.; Oldfield, A.; Sevrac, D.; Dubois, E.; Ritchie, W. J.",,,,True
7607a4ad84452e29998a80f44bfd6bb2f5f68a7f,biorxiv,Viral Architecture of SARS-CoV-2 with Post-Fusion Spike Revealed by Cryo-EM,doi.org/10.1101/2020.03.02.972927,,,See https://www.biorxiv.org/about-biorxiv,"Since December 2019, the outbreak of Coronavirus Disease 2019 (COVID-19) spread from Wuhan, China to the world, it has caused more than 87,000 diagnosed cases and more than 3,000 deaths globally. To fight against COVID-19, we carried out research for the near native SARS-CoV-2 and report here our preliminary results obtained. The pathogen of the COVID-19, the native SARS-CoV-2, was isolated, amplified and purified in a BSL-3 laboratory. The whole viral architecture of SARS-CoV-2 was examined by transmission electron microscopy (both negative staining and cryo-EM). We observed that the virion particles are roughly spherical or moderately pleiomorphic. Spikes have nail-like shape towards outside with a long body embedded in the envelope. The morphology of virion observed in our result indicates that the S protein of SARS-CoV-2 is in post-fusion state, with S1 disassociated. This state revealed by cryo-EM first time could provide an important information for the identification and relevant clinical research of this new coronavirus.",2020-03-05,"Liu, C.; Yang, Y.; Gao, Y.; Shen, C.; Ju, B.; Liu, C.; Tang, X.; Wei, J.; Ma, X.; Liu, W.; Xu, S.; Liu, Y.; Yuan, J.; Wu, J.; Liu, Z.; Zhang, Z.; Wang, P.; Liu, L.",,,,True
f6f1ec12291f743de1504003929ea654217f2af6,biorxiv,Candidate targets for immune responses to 2019-Novel Coronavirus (nCoV): sequence homology- and bioinformatic-based predictions,doi.org/10.1101/2020.02.12.946087,,,See https://www.biorxiv.org/about-biorxiv,"Effective countermeasures against the recent emergence and rapid expansion of the 2019-Novel Coronavirus (2019-nCoV) require the development of data and tools to understand and monitor viral spread and immune responses. However, little information about the targets of immune responses to 2019-nCoV is available. We used the Immune Epitope Database and Analysis Resource (IEDB) resource to catalog available data related to other coronaviruses, including SARS-CoV, which has high sequence similarity to 2019-nCoV, and is the best-characterized coronavirus in terms of epitope responses. We identified multiple specific regions in 2019-nCoV that have high homology to SARS virus. Parallel bionformatic predictions identified a priori potential B and T cell epitopes for 2019-nCoV. The independent identification of the same regions using two approaches reflects the high probability that these regions are targets for immune recognition of 2019-nCoV.  ONE SENTENCE SUMMARYWe identified potential targets for immune responses to 2019-nCoV and provide essential information for understanding human immune responses to this virus and evaluation of diagnostic and vaccine candidates.",2020-03-06,"Grifoni, A.; Sidney, J.; Zhang, Y.; Scheuermann, R. H.; Peters, B. H.; Sette, A.",,,,True
1b4ab28a9391d516e1753874c73d2d244104f825,biorxiv,Functional pangenome analysis suggests inhibition of the protein E as a readily available therapy for COVID-2019.,doi.org/10.1101/2020.02.17.952895,,,See https://www.biorxiv.org/about-biorxiv,"The spread of the novel coronavirus (SARS-CoV-2) has triggered a global emergency, that demands urgent solutions for detection and therapy to prevent escalating health, social and economic impacts. The spike protein (S) of this virus enables binding to the human receptor ACE2, and hence presents a prime target for vaccines preventing viral entry into host cells1. The S proteins from SARS-CoV-1 and SARS-CoV-2 are similar2, but structural differences in the receptor binding domain (RBD) preclude the use of SARS-CoV-1-specific neutralizing antibodies to inhibit SARS-CoV-23. Here we used comparative pangenomic analysis of all sequenced Betacoronaviruses to reveal that, among all core gene clusters present in these viruses, the envelope protein E shows a variant shared by SARS and SARS-Cov2 with two completely-conserved key functional features, an ion-channel and a PDZ-binding Motif (PBM). These features trigger a cytokine storm that activates the inflammasome, leading to increased edema in lungs causing the acute respiratory distress syndrome (ARDS)4-6, the leading cause of death in SARS-CoV-1 and SARS-CoV-2 infection7,8. However, three drugs approved for human use may inhibit SARS-CoV-1 and SARS-CoV-2 Protein E, either acting upon the ion channel (Amantadine and Hexamethylene amiloride9,10) or the PBM (SB2035805), thereby potentially increasing the survival of the host, as already demonstrated for SARS-CoV-1in animal models. Hence, blocking the SARS protein E inhibits development of ARDS in vivo. Given that our results demonstrate that the protein E subcluster for the SARS clade is quasi-identical for the key functional regions of SARS-CoV-1 and SARS-CoV-2, we conclude that use of approved drugs shown to act as SARS E protein inhibitors can help prevent further casualties from COVID-2019 while vaccines and other preventive measures are being developed.",2020-03-06,"Alam, I.; Kamau, A. K.; Kulmanov, M.; Arold, S. T.; Pain, A. T.; Gojobori, T.; Duarte, C. M.",,,,True
20f2a638e2c9a1917b7c001c371335da3d288505,biorxiv,Partial RdRp sequences offer a robust method for Coronavirus subgenus classification,doi.org/10.1101/2020.03.02.974311,,,See https://www.biorxiv.org/about-biorxiv,"The recent reclassification of the Riboviria, and the introduction of multiple new taxonomic categories including both subfamilies and subgenera for coronaviruses (family Coronaviridae, subfamily Orthocoronavirinae) represents a major shift in how official classifications are used to designate specific viral lineages. While the newly defined subgenera provide much-needed standardisation for commonly cited viruses of public health importance, no method has been proposed for the assignment of subgenus based on partial sequence data, or for sequences that are divergent from the designated holotype reference genomes. Here, we describe the genetic variation of a partial region of the coronavirus RNA-dependent RNA polymerase (RdRp), which is one of the most used partial sequence loci for both detection and classification of coronaviruses in molecular epidemiology. We infer Bayesian phylogenies from more than 7000 publicly available coronavirus sequences and examine clade groupings relative to all subgenus holotype sequences. Our phylogenetic analyses are largely coherent with genome-scale analyses based on designated holotype members for each subgenus. Distance measures between sequences form discrete clusters between taxa, offering logical threshold boundaries that can attribute subgenus or indicate sequences that are likely to belong to unclassified subgenera both accurately and robustly. We thus propose that partial RdRp sequence data of coronaviruses is sufficient for the attribution of subgenus-level taxonomic classifications and we supply the R package, ""MyCoV"", which provides a method for attributing subgenus and assessing the reliability of the attribution.  Importance StatementThe analysis of polymerase chain reaction amplicons derived from biological samples is the most common modern method for detection and classification of infecting viral agents, such as Coronaviruses. Recent updates to the official standard for taxonomic classification of Coronaviruses, however, may leave researchers unsure as to whether the viral sequences they obtain by these methods can be classified into specific viral taxa due to variations in the sequences when compared to type strains. Here, we present a plausible method for defining genetic dissimilarity cut-offs that will allow researchers to state which taxon their virus belongs to and with what level of certainty. To assist in this, we also provide the R package  MyCoV which classifies user generated sequences.",2020-03-06,"Wilkinson, D. A.; Joffrin, L.; Lebarbenchon, C.; Mavingui, P.",,,,True
73c8af41cfdbf52c0dfba37727e3b94cb56b495e,biorxiv,The Essential Facts of Wuhan Novel Coronavirus Outbreak in China and Epitope-based Vaccine Designing against COVID-19,doi.org/10.1101/2020.02.05.935072,,,See https://www.biorxiv.org/about-biorxiv,"Wuhan Novel Coronavirus disease (COVID-19) outbreak has become a global outbreak which has raised the concern of scientific community to design and discover a definitive cure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading. To date, no antiviral therapy or vaccine is available which can effectively combat the infection caused by this virus. This study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against SARS-CoV-2. Later, molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. Hopefully, this study will contribute to uphold the present efforts of the researches to secure a definitive treatment against this lethal virus.",2020-03-06,"Sarkar, B.; Ullah, M. A.; Johora, F. T.; Taniya, M. A.; Araf, Y.",,,,True
fd14ed7c073b7ff03afa517e9c0fd1e849878252,biorxiv,Direct RNA sequencing and early evolution of SARS-CoV-2,doi.org/10.1101/2020.03.05.976167,,,See https://www.biorxiv.org/about-biorxiv,"The rapid sharing of sequence information as seen throughout the current SARS-CoV-2 epidemic, represents an inflection point for genomic epidemiology. Here we describe aspects of coronavirus evolutionary genetics revealed from these data, and provide the first direct RNA sequence of SARS-CoV-2, detailing coronaviral subgenome-length mRNA architecture.",2020-03-07,"Taiaroa, G.; Rawlinson, D.; Featherstone, L.; Pitt, M.; Caly, L.; Druce, J.; Purcell, D.; Harty, L.; Tran, T.; Roberts, J.; Catton, M.; Williamson, D.; Coin, L.; Duchene, S.",,,,True
6726b273f345838661eaa39e8adb5df4e1815a9a,biorxiv,"In silico study of the spike protein from SARS-CoV-2 interaction with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism",doi.org/10.1101/2020.03.04.976027,,,See https://www.biorxiv.org/about-biorxiv,"The spread of the COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor via which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. We used homology-based protein-protein docking, binding energy estimation, and decomposition, aiming to predict both qualitative and quantitative aspects of the interaction. Using in silico structural modelling, we brought additional evidence that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than mutation accumulation. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to hACE2 and maintaining the stability of the interface. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.",2020-03-07,"Othman, H.; Bouslama, Z.; Brandenburg, J.-T.; da Rocha, J.; Hamdi, Y.; Ghedira, K.; Abid, N.-S.; Hazelhurst, S.",,,,True
f19467ad896da62d9f35816c4d54d75c0237d99d,biorxiv,Isolation and characterization of SARS-CoV-2 from the first US COVID-19 patient,doi.org/10.1101/2020.03.02.972935,,,See https://www.biorxiv.org/about-biorxiv,"The etiologic agent of the outbreak of pneumonia in Wuhan China was identified as severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) in January, 2020. The first US patient was diagnosed by the State of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens, and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into two virus repositories, making it broadly available to the public health and research communities. We hope that open access to this important reagent will expedite development of medical countermeasures.  Article SummaryScientists have isolated virus from the first US COVID-19 patient. The isolation and reagents described here will serve as the US reference strain used in research, drug discovery and vaccine testing.",2020-03-07,"Harcourt, J.; Tamin, A.; Lu, X.; Kamili, S.; Kumar Sakthivel, S.; Wang, L.; Murray, J.; Queen, K.; Lynch, B.; Whitaker, B.; Tao, Y.; Paden, C.; Zhang, J.; Li, Y.; Uehara, A.; Wang, H.; Goldsmith, C.; Bullock, H.; Gautam, R.; Schindewolf, C.; Lokugamage, K. G.; Scharton, D.; Plante, J.; Mirchandani, D.; Widen, S.; Narayanan, K.; Makino, S.; Ksiazek, T.; Plante, K. S.; Weaver, S.; Menachery, V. D.; Thornburg, N. J.",,,,False
d23c6a066a58dbe5ec5fa57e67f1b795337299f7,biorxiv,LY6E impairs coronavirus fusion and confers immune control of viral disease,doi.org/10.1101/2020.03.05.979260,,,See https://www.biorxiv.org/about-biorxiv,"Zoonotic coronaviruses (CoVs) are significant threats to global health, as exemplified by the recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. Host immune responses to CoV are complex and regulated in part through antiviral interferons. However, the interferon-stimulated gene products that inhibit CoV are not well characterized2. Here, we show that interferon-inducible lymphocyte antigen 6 complex, locus E (LY6E) potently restricts cellular infection by multiple CoVs, including SARS-CoV, SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV). Mechanistic studies revealed that LY6E inhibits CoV entry into cells by interfering with spike protein-mediated membrane fusion. Importantly, mice lacking Ly6e in hematopoietic cells were highly susceptible to murine CoV infection. Exacerbated viral pathogenesis in Ly6e knockout mice was accompanied by loss of hepatic and splenic immune cells and reduction in global antiviral gene pathways. Accordingly, we found that Ly6e directly protects primary B cells and dendritic cells from murine CoV infection. Our results demonstrate that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis. These findings advance our understanding of immune-mediated control of CoV in vitro and in vivo, knowledge that could help inform strategies to combat infection by emerging CoV.",2020-03-07,"Pfaender, S.; Mar, K. B.; Michailidis, E.; Kratzel, A.; Hirt, D.; V'kovski, P.; Fan, W.; Ebert, N.; Stalder, H.; Kleine-Weber, H.; Hoffmann, M.; Hoffmann, H. H.; Saeed, M.; Dijkman, R.; Steinmann, E.; Wight-Carter, M.; Hanners, N. W.; Pohlmann, S.; Gallagher, T.; Todt, D.; Zimmer, G.; Rice, C. M.; Schoggins, J. W.; Thiel, V.",,,,True
a33f451d8e2caff57c1133f14198454a64993c47,biorxiv,Monoclonal antibodies for the S2 subunit of spike of SARS-CoV cross-react with the newly-emerged SARS-CoV-2,doi.org/10.1101/2020.03.06.980037,,,See https://www.biorxiv.org/about-biorxiv,"The emergence of a novel coronavirus, SARS-CoV-2, at the end of 2019 has resulted in widespread human infections across the globe. While genetically distinct from SARS-CoV, the etiological agent that caused an outbreak of severe acute respiratory syndrome (SARS) in 2003, both coronaviruses exhibit receptor binding domain (RBD) conservation and utilize the same host cell receptor, angiotensin-converting enzyme 2 (ACE2), for virus entry. Therefore, it will be important to test the cross-reactivity of antibodies that have been previously generated against the surface spike (S) glycoprotein of SARS-CoV in order to aid research on the newly emerged SARS-CoV-2. Here, we show that an immunogenic domain in the S2 subunit of SARS-CoV S is highly conserved in multiple strains of SARS-CoV-2. Consistently, four murine monoclonal antibodies (mAbs) raised against this immunogenic SARS-CoV fragment were able to recognise the S protein of SARS-CoV-2 expressed in a mammalian cell line. Importantly, one of them (mAb 1A9) was demonstrated to detect S in SARS-CoV-2-infected cells. To our knowledge, this is the first study showing that mAbs targeting the S2 domain of SARS-CoV can cross-react with SARS-CoV-2 and this observation is consistent with the high sequence conservation in the S2 subunit. These cross-reactive mAbs may serve as tools useful for SARS-CoV-2 research as well as for the development of diagnostic assays for its associated coronavirus disease COVID-19.",2020-03-07,"Zheng, Z.; Monteil, V. M.; Maurer-Stroh, S.; Yew, C. W.; Leong, C.; Mohd-Ismail, N. K.; Arularasu, S. C.; Chow, V. T. K.; Lin, R. T. P.; Mirazimi, A.; Hong, W.; Tan, Y.-J.",,,,True
e350e1b4aab99c73d0e0d03121b50c059c04fd61,biorxiv,Novel Immunoglobulin Domain Proteins Provide Insights into Evolution and Pathogenesis Mechanisms of SARS-Related Coronaviruses,doi.org/10.1101/2020.03.04.977736,,,See https://www.biorxiv.org/about-biorxiv,"A novel coronavirus (SARS-CoV-2) is the causative agent of an emergent severe respiratory disease (COVID-19) in humans that is threatening to result in a global health crisis. By using genomic, sequence, structural and evolutionary analysis, we show that Alpha- and Beta-CoVs possess several novel families of immunoglobulin (Ig) domain proteins, including ORF8 and ORF7a from SARS-related coronaviruses and two protein groups from certain Alpha-CoVs. Among them, ORF8 is distinguished in being rapidly evolving, possessing a unique insert and a hypervariable position among SARS-CoV-2 genomes in its predicted ligand-binding groove. We also uncover many Ig proteins from several metazoan viruses which are distinct in sequence and structure but share an architecture comparable to that of CoV Ig domain proteins. Hence, we propose that deployment of Ig domain proteins is a widely-used strategy by viruses, and SARS-CoV-2 ORF8 is a potential pathogenicity factor which evolves rapidly to counter the immune response and facilitate the transmission between hosts.",2020-03-07,"Tan, Y.; Schneider, T.; Leong, M.; Aravind, L.; Zhang, D.",,,,True
38e796bbec2f90b1b802c14dc922102e96f6361e,biorxiv,The within-host viral kinetics of SARS-CoV-2,doi.org/10.1101/2020.02.29.965418,,,See https://www.biorxiv.org/about-biorxiv,"In this work, we use a within-host viral dynamic model to describe the SARS-CoV-2 kinetics in host. Chest radiograph score data are used to estimate the parameters of that model. Our result shows that the basic reproductive number of SARS-CoV-2 in host growth is around 3.79. Using the same method we also estimate the basic reproductive number of MERS virus is 8.16 which is higher than SARS-CoV-2. The PRCC method is used to analyze the sensitivities of model parameters and the drug effects on virus growth are also implemented to analyze the model.",2020-03-07,"Li, C.; Xu, J.; Liu, J.; Zhou, Y.",,,,True
8349823092836fe397a59e38615d1491423dbe70,biorxiv,AI-aided design of novel targeted covalent inhibitors against SARS-CoV-2,doi.org/10.1101/2020.03.03.972133,,,See https://www.biorxiv.org/about-biorxiv,"The focused drug repurposing of known approved drugs (such as lopinavir/ritonavir) has been reported failed for curing SARS-CoV-2 infected patients. It is urgent to generate new chemical entities against this virus. As a key enzyme in the life-cycle of coronavirus, the 3C-like main protease (3CLpro or Mpro) is the most attractive for antiviral drug design. Based on a recently solved structure (PDB ID: 6LU7), we developed a novel advanced deep Q-learning network with the fragment-based drug design (ADQN-FBDD) for generating potential lead compounds targeting SARS-CoV-2 3CLpro. We obtained a series of derivatives from those lead compounds by our structure-based optimization policy (SBOP). All the 47 lead compounds directly from our AI-model and related derivatives based on SBOP are accessible in our molecular library at https://github.com/tbwxmu/2019-nCov. These compounds can be used as potential candidates for researchers in their development of drugs against SARS-CoV-2.",2020-03-08,"Tang, B.; He, F.; Liu, D.; Fang, M.; Wu, Z.; Xu, D.",,,,True
5cf2bec1530cef38cd0eea173fb90ba1a788e11f,biorxiv,Assessing Topographic Structural Connectivity of the Human Basal Ganglia and Thalamus,doi.org/10.1101/2020.03.06.981142,,,See https://www.biorxiv.org/about-biorxiv,"The basal ganglia and thalamus play an important role in cognition, procedural learning, eye movements, control of voluntary motor movements, emotional control, habit development, and are structures that are severely impacted by neurological disorders such as Alzheimers disease, Parkinsons disease, or Tourette syndrome. To understand the structural connectivity of cortical and subcortical circuits in the healthy human brain could thus be of pivotal importance for detecting changes in this circuitry and to start early intervention, to assess the progress of movement rehabilitation, or the effectiveness of therapeutic approaches in neuropsychiatry. While conventional magnetic resonance imaging (MRI), positron emission tomography, or magnetoencephalography are able to provide detailed information about connectivity at the macro level, the sensitivity and specificity these imaging techniques put limits on the amount of detail one can obtain when measuring in vivo connectivity of human basal ganglia and thalamus. In contrast, the multiband diffusion echo planar imaging MRI sequence, which acquires multiple slices of the brain simultaneously, enables high resolution imaging of these brain structures with only short acquisition times at 3-Tesla field strength. Here, we introduce a novel protocol that allows us to generate comprehensive in vivo participant-specific probabilistic patterns and visualizations of the structural connections that exist within basal ganglia and thalamic nuclei. Moreover, we are able to map specific parcellations of these nuclei into sub-territories based on their connectivity with primary motor-, and somatosensory cortex. The detailed subcortical structural connectivity mapping introduced in this work could benefit early intervention and therapy methods for human movement rehabilitation and for treating neuropsychiatric disorders.",2020-03-08,"Gilani, I. A.; Oguz, K. K.; Boyaci, H.; Doerschner, K.",,,,True
4f3d6010cea5322e31ea6785a8fa1f9265e4d44a,biorxiv,Meta-transcriptomic analysis of virus diversity in urban wild birds with paretic disease,doi.org/10.1101/2020.03.07.982207,,,See https://www.biorxiv.org/about-biorxiv,"Wild birds are major natural reservoirs and potential dispersers of a variety of infectious diseases. As such, it is important to determine the diversity of viruses they carry and use this information to help understand the potential risks of spill-over to humans, domestic animals, and other wildlife. We investigated the potential viral causes of paresis in long-standing, but undiagnosed disease syndromes in wild Australian birds. RNA from diseased birds was extracted and pooled based on tissue type, host species and clinical manifestation for metagenomic sequencing. Using a bulk and unbiased meta-transcriptomic approach, combined with careful clinical investigation and histopathology, we identified a number of novel viruses from the families Astroviridae, Picornaviridae, Polyomaviridae, Paramyxoviridae, Parvoviridae, Flaviviridae, and Circoviridae in common urban wild birds including Australian magpies, magpie lark, pied currawongs, Australian ravens, and rainbow lorikeets. In each case the presence of the virus was confirmed by RT-PCR. These data revealed a number of candidate viral pathogens that may contribute to coronary, skeletal muscle, vascular and neuropathology in birds of the Corvidae and Artamidae families, and neuropathology in members of the Psittaculidae. The existence of such a diverse virome in urban avian species highlights the importance and challenges in elucidating the etiology and ecology of wildlife pathogens in urban environments. This information will be increasingly important for managing disease risks and conducting surveillance for potential viral threats to wildlife, livestock and human health. More broadly, our work shows how meta-transcriptomics brings a new utility to pathogen discovery in wildlife diseases.  ImportanceWildlife naturally harbor a diverse array of infectious microorganisms and can be a source of novel diseases in domestic animals and human populations. Using unbiased RNA sequencing we identified highly diverse viruses in native birds in Australian urban environments presenting with paresis. This investigation included the clinical investigation and description of poorly understood recurring syndromes of unknown etiology: clenched claw syndrome, and black and white bird disease. As well as identifying a range of potentially disease-causing viral pathogens, this study describes methods that can effectively and efficiently characterize emergent disease syndromes in free ranging wildlife, and promotes further surveillance for specific potential pathogens of potential conservation and zoonotic concern.",2020-03-08,"Chang, W.-S.; Eden, J.-S.; Hall, J.; Shi, M.; Rose, K.; Holmes, E. C.",,,,False
3ebbcdddb122f405061bb5e1ddcf94abe9258d58,biorxiv,Substrate specificity profiling of SARS-CoV-2 Mpro protease provides basis for anti-COVID-19 drug design,doi.org/10.1101/2020.03.07.981928,,,See https://www.biorxiv.org/about-biorxiv,"In December 2019, the first cases of a novel coronavirus infection were diagnosed in Wuhan, China. Due to international travel and human-to-human transmission, the virus spread rapidly inside and outside of China. Currently, there is no effective antiviral treatment for COVID-19, therefore research efforts are focused on the rapid development of vaccines and antiviral drugs. The SARS-CoV-2 Mpro protease constitutes one of the most attractive antiviral drug targets. To address this emerging problem, we have synthesized a combinatorial library of fluorogenic substrates with glutamine in the P1 position. We used it to determine the substrate preferences of the SARS-CoV and SARS-CoV-2 proteases, using natural and a large panel of unnatural amino acids. The results of our work provide a structural framework for the design of inhibitors as antiviral agents or diagnostic tests.",2020-03-08,"Rut, W.; Groborz, K.; Zhang, L.; Sun, X.; Zmudzinski, M.; Hilgenfeld, R.; Drag, M.",,,,True
e476334b4f415f8fde5e2f560fd1ad0fa314af90,biorxiv,A single locus underlies variation in Caenorhabditis elegans chemotherapeutic responses,doi.org/10.1101/2020.03.09.984393,,,See https://www.biorxiv.org/about-biorxiv,"Pleiotropy, the concept that a single gene controls multiple distinct traits, is prevalent in most organisms and has broad implications for medicine and agriculture. Identifying the molecular mechanisms underlying pleiotropy has the power to unveil previously unknown biological connections between seemingly unrelated traits. Additionally, the discovery of pleiotropic genes increases our understanding of both genetic and phenotypic complexity by characterizing novel gene functions. Quantitative trait locus (QTL) mapping has been used to identify several pleiotropic regions in many organisms. However, gene knockout studies are needed to eliminate the possibility of tightly linked, non-pleiotropic loci. Here, we use a panel of 296 recombinant inbred advanced intercross lines of Caenorhabditis elegans and a high-throughput fitness assay to identify a single large-effect QTL on the center of chromosome V associated with variation in responses to eight chemotherapeutics. We validate this QTL with near-isogenic lines and pair genome-wide gene expression data with drug response traits to perform mediation analysis, leading to the identification of a pleiotropic candidate gene, scb-1. Using deletion strains created by genome editing, we show that scb-1, which was previously implicated in response to bleomycin, also underlies responses to other double-strand DNA break-inducing chemotherapeutics. This finding provides new evidence for the role of scb-1 in the nematode drug response and highlights the power of mediation analysis to identify causal genes.",2020-03-09,"Andersen, E.; Evans, K. S.",,,,True
a2a6e262098539eb875a26800d9f6d3d0d5d1875,biorxiv,An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors' CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design,doi.org/10.1101/2020.02.25.963546,,,See https://www.biorxiv.org/about-biorxiv,The 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within COVID-19 contain multiple class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus.,2020-03-09,"Herst, C. V.; Burkholz, S.; Sidney, J.; Sette, A.; Harris, P. E.; Massey, S.; Brasel, T.; Cunha-Neto, E.; Rosa, D. S.; Chao, W. C. H.; Carback, R. T.; Hodge, T.; Wang, L.; Ciotlos, S.; Lloyd, P.; Rubsamen, R. M.",,,,True
da3aa20131ac2805c0d9e1b29f094683479ab5b7,biorxiv,Ruler elements in chromatin remodelers set nucleosome array spacing and phasing,doi.org/10.1101/2020.02.28.969618,,,See https://www.biorxiv.org/about-biorxiv,"Arrays of regularly spaced nucleosomes dominate chromatin and are often phased by alignment to reference sites like active promoters. How the distances between nucleosomes (spacing), and between phasing sites and nucleosomes are determined remains unclear, and specifically, how ATP dependent chromatin remodelers impact these features. Here, we used genome-wide reconstitution to probe how Saccharomyces cerevisiae ATP dependent remodelers generate phased arrays of regularly spaced nucleosomes. We find that remodelers bear a functional element named the  ruler that determines spacing and phasing in a remodeler-specific way. We use structure-based mutagenesis to identify and tune the ruler element residing in the Nhp10 and Arp8 modules of the INO80 remodeler complex. Generally, we propose that a remodeler ruler regulates nucleosome sliding direction bias in response to (epi)genetic information. This finally conceptualizes how remodeler-mediated nucleosome dynamics determine stable steady-state nucleosome positioning relative to other nucleosomes, DNA bound factors, DNA ends and DNA sequence elements.",2020-03-09,"Oberbeckmann, E.; Niebauer, V.; Watanabe, S.; Farnung, L.; Moldt, M.; Schmid, A.; Cramer, P.; Peterson, C. L.; Eustermann, S.; Hopfner, K.-P.; Korber, P.",,,,True
960732b8d97d746a065188436b88f8b26af9ab4b,biorxiv,SARS-CoV-2 sensitive to type I interferon pretreatment.,doi.org/10.1101/2020.03.07.982264,,,See https://www.biorxiv.org/about-biorxiv,"SARS-CoV-2, a novel coronavirus (CoV), has recently emerged causing an ongoing outbreak of viral pneumonia around the world. While genetically distinct from the original SARS-CoV, both group 2B coronaviruses share similar genome organization and origins to coronaviruses harbored in bats. Importantly, initial guidance has used insights from SARS-CoV infection to inform treatment and public health strategies. In this report, we evaluate SARS-CoV-2 relative to the original SARS-CoV. Our results indicate that while SARS-CoV-2 maintains similar viral replication kinetics to SARS-CoV in Vero cell, the novel coronavirus is much more sensitive to type I interferon pretreatment. We subsequently examined homology between SARS-CoV and SARS-CoV-2 in viral proteins shown to be interferon antagonist. The absence of open reading frame (ORF) 3b and significant changes to ORF6 suggest the two key IFN antagonists may not maintain equivalent function in SARS-CoV-2. Together, the results identify key differences in susceptibility to the IFN response between SARS-CoV and SARS-CoV-2 that could help inform disease progression, treatment options, and animal model development.",2020-03-09,"Lokugamage, K. G.; Schindewolf, C.; Menachery, V. D.",,,,True
16a7fa1f469a4bc6049eba6a2e335caeca4dfec8,biorxiv,A proposal of an alternative primer for the ARTIC Network's multiplex PCR to improve coverage of SARS-CoV-2 genome sequencing,doi.org/10.1101/2020.03.10.985150,,,See https://www.biorxiv.org/about-biorxiv,"A group of biologists, ARTIC Network, has proposed a multiplexed PCR primer set for whole genome analysis of the novel corona virus, SARS-CoV-2, soon after the epidemics of this pathogen was revealed. The primer set seems to have been adapted already by many researchers worldwide and contributed for the high-quality and prompt genome epidemiology of this potential pandemic virus. We have also seen the great performance of their primer set and protocol; the primer set was able to amplify all desired PCR products with fairy small amplification bias from clinical samples with relatively high viral load. However, we observed acute drop of reads derived from two particular PCR products, 18 and 76, out of the 98 designated products as sample's viral load decreases. We suspected the reason for this low coverage issue was due to dimer formation between primers used to amplify those two PCR products. Here, we propose replacing just one of those primers, nCoV-2019_76_RIGHT(-), to a newly designed primer. The result of the replacement of primer showed improvement in coverage at both regions targeted by the products, 18 and 76. We expect this simple modification will extend the limit for whole SARS-CoV-2 genome analysis to samples with lower viral load and enhance genomic epidemiology of this pathogen.",2020-03-10,"Itokawa, K.; Sekizuka, T.; Hashino, M.; Tanaka, R.; Kuroda, M.",,,,False
2989bf36068372cfedef82f58f4777e60ccbcfaa,biorxiv,Aerodynamic Characteristics and RNA Concentration of SARS-CoV-2 Aerosol in Wuhan Hospitals during COVID-19 Outbreak,doi.org/10.1101/2020.03.08.982637,,,See https://www.biorxiv.org/about-biorxiv,"Background: The ongoing outbreak of COVID-19 has spread rapidly and sparked global concern. While the transmission of SARS-CoV-2 through human respiratory droplets and contact with infected persons is clear, the aerosol transmission of SARS-CoV-2 has been little studied. Methods: Thirty-five aerosol samples of three different types (total suspended particle, size segregated and deposition aerosol) were collected in Patient Areas (PAA) and Medical Staff Areas (MSA) of Renmin Hospital of Wuhan University (Renmin) and Wuchang Fangcang Field Hospital (Fangcang), and Public Areas (PUA) in Wuhan, China during COVID-19 outbreak. A robust droplet digital polymerase chain reaction (ddPCR) method was employed to quantitate the viral SARS-CoV-2 RNA genome and determine aerosol RNA concentration. Results: The ICU, CCU and general patient rooms inside Renmin, patient hall inside Fangcang had undetectable or low airborne SARS-CoV-2 concentration but deposition samples inside ICU and air sample in Fangcang patient toilet tested positive. The airborne SARS-CoV-2 in Fangcang MSA had bimodal distribution with higher concentration than those in Renmin during the outbreak but turned negative after patients number reduced and rigorous sanitization implemented. PUA had undetectable airborne SARS-CoV-2 concentration but obviously increased with accumulating crowd flow. Conclusions: Room ventilation, open space, proper use and disinfection of toilet can effectively limit aerosol transmission of SARS-CoV-2. Gathering of crowds with asymptomatic carriers is a potential source of airborne SARS-CoV-2. The virus aerosol deposition on protective apparel or floor surface and their subsequent resuspension is a potential transmission pathway and effective sanitization is critical in minimizing aerosol transmission of SARS-CoV-2.",2020-03-10,"Liu, Y.; Ning, Z.; Chen, Y.; Guo, M.; Liu, Y.; Gali, N. K.; Sun, L.; Duan, Y.; Cai, J.; Westerdahl, D.; Liu, X.; Ho, K.-f.; Kan, H.; Fu, Q.; Lan, K.",,,,True
b4d9a00412c65725de441654454803bb20ecb931,biorxiv,In silico approach to accelerate the development of mass spectrometry-based proteomics methods for detection of viral proteins: Application to COVID-19,doi.org/10.1101/2020.03.08.980383,,,See https://www.biorxiv.org/about-biorxiv,"The novel coronavirus disease first identified in 2019 in Wuhan, China (COVID-19) has become a serious global public health concern. One current issue is the ability to adequately screen for the virus causing COVID-2 (SARS-CoV-2). Here we demonstrate the feasibility of shotgun proteomics as a SARS-CoV-2 screening method, through the detection of viral peptides in proteolytically digested body fluids. Using in silico methods, we generated trypsin-based shotgun proteomics methods optimized for LCMS systems from 5 commercial instrument vendors (Thermo, SCIEX, Waters, Shimadzu, and Agilent). First, we generated protein FASTA files and their protein digest maps. Second, the FASTA files were used to generate spectral libraries based on experimental data. Third, transition lists were derived from the spectral libraries using the vendor neutral and open Skyline software environment. Finally, we identified 17 post-translational modifications using linear motif modeling.",2020-03-10,"Jenkins, C.; Orsburn, B.",,,,True
82468c289eb562a3e63d084238c08f62e617eb64,biorxiv,In silico Design of novel Multi-epitope recombinant Vaccine based on Coronavirus surface glycoprotein,doi.org/10.1101/2020.03.10.985499,,,See https://www.biorxiv.org/about-biorxiv,"It is of special significance to find a safe and effective vaccine against coronavirus disease 2019 (COVID-19) that can induce T cell and B cell -mediated immune responses. There is currently no vaccine to prevent COVID-19. In this project, a novel multi-epitope vaccine for COVID-19 virus based on surface glycoprotein was designed through application of bioinformatics methods. At the first, seventeen potent linear B-cell and T-cell binding epitopes from surface glycoprotein were predicted in silico, then the epitopes were joined together via different linkers. The immunogenicity of these epitopes was identified using IFN-{gamma} ELIspot assays. The IFN-{gamma} producing T cell variation ranged from 11.1 {+/-}1.2 SFU to 38.2 {+/-} 2.1 SFU per 10 6 PBMCs. One final vaccine was constructed which composed of 398 amino acids and attached to 50S ribosomal protein L7/L12 as adjuvant. Physicochemical properties, as well as antigenicity in the proposed vaccines, were checked for defining the vaccine stability and its ability to induce cell-mediated immune responses. Three-dimensional structure of the mentioned vaccine was subjected to the molecular docking studies with MHC-I and MHC-II molecules. The results proposed that the multi-epitope vaccine with 50S ribosomal protein L7/L12 was very stable with high aliphatic content and high antigenicity.",2020-03-10,"Behbahani, M.",,,,True
278e2c52630f1dbbda6a79db15a2260510586150,biorxiv,PhyloFold: Precise and Swift Prediction of RNA Secondary Structures to Incorporate Phylogeny among Homologs,doi.org/10.1101/2020.03.05.975797,,,See https://www.biorxiv.org/about-biorxiv,"Motivation: The simultaneous consideration of sequence alignment and RNA secondary structure, or structural alignment, is known to help predict more accurate secondary structures of homologs. However, the consideration is heavy and can be done only roughly to decompose structural alignments. Results: The PhyloFold method, which predicts secondary structures of homologs considering likely pairwise structural alignments, was developed in this study. The method shows the best prediction accuracy while demanding comparable running time compared to conventional methods. Availability: The source code of the programs implemented in this study is available on ""https://github.com/heartsh/phylofold"" and ""https://github.com/heartsh/phyloalifold"". Contact: ""tagashira_masaki_17@stu-cbms.k.u-tokyo.ac.jp"".",2020-03-10,"Tagashira, M.",,,,True
313dd0869f169624e78d770963eacb0d1641cafa,biorxiv,Structure of Mpro from COVID-19 virus and discovery of its inhibitors,doi.org/10.1101/2020.02.26.964882,,,See https://www.biorxiv.org/about-biorxiv,"A new coronavirus (CoV) identified as COVID-19 virus is the etiological agent responsible for the 2019-2020 viral pneumonia outbreak that commenced in Wuhan. Currently there is no targeted therapeutics and effective treatment options remain very limited. In order to rapidly discover lead compounds for clinical use, we initiated a program of combined structure-assisted drug design, virtual drug screening and high-throughput screening to identify new drug leads that target the COVID-19 virus main protease (Mpro). Mpro is a key CoV enzyme, which plays a pivotal role in mediating viral replication and transcription, making it an attractive drug target for this virus. Here, we identified a mechanism-based inhibitor, N3, by computer-aided drug design and subsequently determined the crystal structure of COVID-19 virus Mpro in complex with this compound. Next, through a combination of structure-based virtual and high-throughput screening, we assayed over 10,000 compounds including approved drugs, drug candidates in clinical trials, and other pharmacologically active compounds as inhibitors of Mpro. Six of these inhibit Mpro with IC50 values ranging from 0.67 to 21.4 M. Ebselen also exhibited strong antiviral activity in cell-based assays. Our results demonstrate the efficacy of this screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases where no specific drugs or vaccines are available.",2020-03-10,"Jin, Z.; Du, X.; Xu, Y.; Deng, Y.; Liu, M.; Zhao, Y.; Zhang, B.; Li, X.; Zhang, L.; Peng, C.; Duan, Y.; Yu, J.; Wang, L.; Yang, K.; Liu, F.; Jiang, R.; Yang, X.; You, T.; Liu, X.; Yang, X.; Bai, F.; Liu, H.; Liu, X.; Guddat, L. W.; Xu, W.; Xiao, G.; Qin, C.; Shi, Z.; Jiang, H.; Rao, Z.; Yang, H.",,,,True
cddff59aa11d3d8005e389b47cb7c4501a21d593,biorxiv,A novel bat coronavirus reveals natural insertions at the S1/S2 cleavage site of the Spike protein and a possible recombinant origin of HCoV-19,doi.org/10.1101/2020.03.02.974139,,,See https://www.biorxiv.org/about-biorxiv,"The unprecedented epidemic of pneumonia caused by a novel coronavirus, HCoV-19, in China and beyond has caused public health concern at a global scale. Although bats are regarded as the most likely natural hosts for HCoV-19, the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomics analysis of samples from 227 bats collected from Yunnan Province in China between May and October, 2019. RmYN02 shared 93.3% nucleotide identity with HCoV-19 at the scale of the complete virus genome and 97.2% identity in the 1ab gene in which it was the closest relative of HCoV-19. In contrast, RmYN02 showed low sequence identity (61.3%) to HCoV-19 in the receptor binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, however, and in a similar manner to HCoV-19, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the Spike (S) protein. This provides strong evidence that such insertion events can occur in nature. Together, these data suggest that HCoV-19 originated from multiple naturally occurring recombination events among those viruses present in bats and other wildlife species.",2020-03-11,"Zhou, H.; Chen, X.; Hu, T.; Li, J.; Song, H.; Liu, Y.; Wang, P.; Liu, D.; Yang, J.; Holmes, E. C.; Hughes, A. C.; Bi, Y.; Shi, W.",,,,True
780fc85ab807f33f706a38c86480e284da800cb8,biorxiv,Cryo-electron microscopy structure of the SADS-CoV spike glycoprotein provides insights into an evolution of unique coronavirus spike proteins,doi.org/10.1101/2020.03.04.976258,,,See https://www.biorxiv.org/about-biorxiv,"The outbreak of a novel betacoronavirus (SARS-CoV-2) has aroused great public health concern. As a new coronavirus which was responsible for a large-scale outbreak of fatal disease in piglets in China, swine acute diarrhea syndrome coronavirus (SADS-CoV) originated from the same genus of horseshoe bats (Rhinolophus) as SARS-CoV and possesses a broad species tropism. In addition to human cells, it can also infect cell lines from diverse species. Given the importance of the spike glycoprotein (S) protein in viral entry and host immune responses, here we report the cryo-EM structure of the SADS-CoV S in the prefusion conformation at a resolution of 3.55 angstrom. Our studies reveal that SADS-CoV S structure takes an intra-subunit quaternary packing mode where the NTD and CTD from the same subunit pack together by facing each other. The comparison of NTD and CTD with that of the other four genera gives the suggestion of the evolutionary procedure of the SADS-CoV S. Moreover, SADS-CoV S has several characteristic structural features, i.e., more compact architecture of S trimer, masking of epitopes by glycan shielding, which may facilitate to viral immune evasion. These data provide new insights into the evolutionary relationships of SADS-CoV S and would deepen our understanding of their structural and functional diversity which will facilitate to vaccine development.",2020-03-11,"Ouyang, S.",,,,True
854a29cd858f64982c799eb27c0a45cb762adfa8,biorxiv,Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites,doi.org/10.1101/2020.03.06.977876,,,See https://www.biorxiv.org/about-biorxiv,"The outbreak of coronavirus disease (COVID-19) in China caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. It is currently no specific viral protein targeted therapeutics yet. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein is yet to be clear. Herein, we have determined the crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although overall structure is similar with other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the beta-sheet core. Complemented by in vitro binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.",2020-03-11,"Kang, S.; Yang, M.; Hong, Z.; Zhang, L.; Huang, Z.; Chen, X.; He, S.; Zhou, Z.; Zhou, Z.; Chen, Q.; Yan, Y.; Zhang, C.; Shan, H.; Chen, S.",,,,True
dfb2f07149617b0c2911899ac61563e808e2cee1,biorxiv,Genome-wide data inferring the evolution and population demography of the novel pneumonia coronavirus (SARS-CoV-2),doi.org/10.1101/2020.03.04.976662,,,See https://www.biorxiv.org/about-biorxiv,"Since December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan, Central China and rapidly spread throughout China. Up to March 3, 2020, SARS-CoV-2 has infected more than 89,000 people in China and other 66 countries across six continents. In this study, we used 10 new sequenced genomes of SARS-CoV-2 and combined 136 genomes from GISAID database to investigate the genetic variation and population demography through different analysis approaches (e.g. Network, EBSP, Mismatch, and neutrality tests) in the previous three months. The results showed that eighty haplotypes had 183 substitution sites, including 27 parsimony-informative and 156 singletons. Sliding window analyses of genetic diversity suggested a certain range in mutations and variation in genomic abundance of SARS-CoV-2, which could be explaining the existing widespread and high adaptation of the deadly virus. Phylogenetic analysis showed that pangolin may not be an intermediate host. The network indicated that, in the original haplotype (H14), one patient sample lived near the Huanan seafood market (approximately 2 km), which indicating high possibility of the patient having a history of unconscious contact with this market. However, based on this clue, we cannot accurately conclude that whether this market was the origin center of SARS-CoV-2. Additionally, 16 genomes, collected from this market, assigned to 10 haplotypes, indicated a circulating infection within the market in a short term, which would have led to the outbreak of SARS-CoV-2 in Wuhan and other areas. The EBSP results showed that the first estimated expansion date began from 7 December 2019, which indicated that the transmission of SARS-CoV-2 could have begun from person to person in mid to late November.",2020-03-11,"Fang, B.; Liu, L.; Yu, X.; Li, X.; Ye, G.; Xu, J.; Zhang, L.; Zhan, F.; Liu, G.; Pan, T.; Shu, Y.; Jiang, Y.",,,,True
ddbf32ef7d7bd337dbfe05cbf8239b0fb698bb6a,biorxiv,The SARS-CoV-2 receptor ACE2 expression of maternal-fetal interface and fetalorgans by single cell transcriptome study,doi.org/10.1101/2020.02.27.967760,,,See https://www.biorxiv.org/about-biorxiv,"Recent studies have demonstrated that SARS-CoV-2 cell entry depends on both ACE2 and TMPRSS2 genes (DOI:10.1016/j.cell.2020.02.052), but our current work only focus on ACE2, which is insufficient to support the conclusion of this paper. So the authors have withdrawn their manuscript whilst they perform additional experiments and analysis to test some of their conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.",2020-03-11,"Li, M.; Chen, L.; Xiong, C.; Li, X.",,,,True
598b8f280571ace476ad56a469e7959918fa7958,biorxiv,Tilorone: A Broad-Spectrum Antiviral For Emerging Viruses,doi.org/10.1101/2020.03.09.984856,,,See https://www.biorxiv.org/about-biorxiv,"Tilorone is a 50-year-old synthetic small-molecule compound with antiviral activity that is proposed to induce interferon after oral administration. This drug is used as a broad-spectrum antiviral in several countries of the Russian Federation. We have recently described activity in vitro and in vivo against the Ebola Virus. After a broad screening of additional viruses, we now describe in vitro activity against Chikungunya virus (CHIK) and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV).",2020-03-11,"Ekins, S.; Madrid, P.",,,,True
090b6c8b3df30bc248221869f673a2d970caa1b9,medrxiv,Quantifying the success of measles vaccination campaigns in the Rohingya refugee camps,doi.org/10.1101/19008417,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>In the wake of the Rohingya population's mass migration from Myanmar, one of the world's largest refugee settlements was constructed in Cox's Bazar, Bangladesh to accommodate nearly 900,000 new refugees. Refugee populations are particularly vulnerable to infectious disease outbreaks due to many population and environmental factors. A large measles outbreak, with over 2,500 cases, occurred among the Rohingya population between September and December 2017. Here, we estimate key epidemiological parameters and use a dynamic mathematical model of measles transmission to evaluate the effectiveness of the reactive vaccination campaigns in the refugee camps. We also estimate the potential for subsequent outbreaks under different vaccination coverage scenarios. Our modeling results highlight the success of the vaccination campaigns in rapidly curbing transmission and emphasize the public health importance of maintaining high levels of vaccination in this population, where high birth rates and historically low vaccination coverage rates create suitable conditions for future measles outbreaks.</jats:p>",2019-10-05,"['Taylor Chin', 'Caroline O. Buckee', 'Ayesha S. Mahmud']",,,,True
10525ac89e46be4cb9cb9fd1131d28411a902047,medrxiv,Using Digital Surveillance Tools for Near Real-Time Mapping of the Risk of International Infectious Disease Spread: Ebola as a Case Study,doi.org/10.1101/19011940,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>In our increasingly interconnected world, it is crucial to understand   the risk of an outbreak originating in one country or region and   spreading to the rest of the world. Digital disease surveillance   tools such as ProMED and HealthMap have the potential to serve as   important early warning systems as well as complement the field   surveillance during an ongoing outbreak. Here we present a flexible   statistical model that uses data produced from digital surveillance   tools (ProMED and HealthMap) to forecast short term incidence trends   in a spatially explicit manner. The model was applied to data collected by ProMED and HealthMap during the 2013-2016 West African Ebola epidemic. The model was able to predict each instance of international spread 1 to 4 weeks in advance. Our study highlights the potential and limitations of using   publicly available digital surveillance data for assessing outbreak dynamics in real-time.</jats:p>",2019-11-15,"['Sangeeta Bhatia', 'Britta Lassmann', 'Emily Cohn', 'Malwina Carrion', 'Moritz U.G. Kraemer', 'Mark Herringer', 'John Brownstein', 'Larry Madoff', 'Anne Cori', 'Pierre Nouvellet']",,,,True
b0899a264af548a89d649154aec569889717b295,medrxiv,Stochastic challenges to interrupting helminth transmission,doi.org/10.1101/2019.12.17.19013490,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Predicting the effect of different programmes designed to control both the morbidity induced by helminth infections and parasite transmission is greatly facilitated by the use of mathematical models of transmission and control impact. In such models, it is essential to account for as many sources of uncertainty -- natural, or otherwise -- to ensure robustness in prediction and to accurately depict variation around an expected outcome. In this paper, we investigate how well the standard deterministic models match the predictions made using individual-based stochastic simulations. We also explore how well concepts which derive from deterministic models, such as ‘breakpoints’ in transmission, apply in the stochastic world. Employing an individual based stochastic model framework we also investigate how transmission and control are affected by the migration of infected people into a defined community. To give our study focus we consider the control of soil-transmitted helminths (STH) by mass drug administration (MDA), though our methodology is readily applicable to the other helminth species such as the schistosome parasites and the filarial worms. We show it is possible to define a ‘stochastic breakpoint’ where much noise surrounds the expected deterministic breakpoint. We also discuss the concept of the ‘interruption of transmission’ independent of the ‘breakpoint’ concept where analyses of model behaviour illustrate the current limitations of deterministic models to account for the ‘fade-out’ or transmission extinction behaviour in simulations. The analyses based on migration confirm a relationship between the infected human migration rate per unit of time and the death rate of infective stages that are released into the free-living environment (eggs or larvae depending on the STH species) that create the reservoir of infection which in turn determines the likelihood that control activities aim at chemotherapeutic treatment of the human host will eliminate transmission. The development of a new stochastic simulation code for STH in the form of a publicly-available open-source python package which includes features to incorporate many population stratifications, different control interventions including mass drug administration (with defined frequency, coverage levels and compliance patterns) and inter-village human migration is also described.</jats:p>",2019-12-18,"['Robert J Hardwick', 'Marleen Werkman', 'James E Truscott', 'Roy M Anderson']",,,,True
e93ba7d8a047795d5ec114741f32f5b18e8567c7,medrxiv,Life course exposures continually shape antibody profile and risk of seroconversion to influenza,doi.org/10.1101/2020.01.15.19015693,,,See https://www.medrxiv.org/submit-a-manuscript,,,,,,,True
6cb02c7565f6f74a3d165e14196de5e9e87d2d04,medrxiv,Novel coronavirus 2019-nCoV: early estimation of epidemiological parameters and epidemic predictions,doi.org/10.1101/2020.01.23.20018549,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Since first identified, the epidemic scale of the recently emerged novel coronavirus (2019-nCoV) in Wuhan, China, has increased rapidly, with cases arising across China and other countries and regions. using a transmission model, we estimate a basic reproductive number of 3.11 (95%CI, 2.39-4.13); 58-76% of transmissions must be prevented to stop increasing; Wuhan case ascertainment of 5.0% (3.6-7.4); 21022 (11090-33490) total infections in Wuhan 1 to 22 January.</jats:p>",2020-01-24,"['Jonathan M Read', 'Jessica RE Bridgen', 'Derek AT Cummings', 'Antonia Ho', 'Chris P Jewell']",,,,True
cbc05d14c57b91081970a232ab83bc993f998fe2,medrxiv,Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data,doi.org/10.1101/2020.01.26.20018754,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The geographic spread of 2019 novel coronavirus (COVID-19) infections from the epicenter of Wuhan, China, has provided an opportunity to study the natural history of the recently emerged virus. Using publicly available event-date data from the ongoing epidemic, the present study investigated the incubation period and other time intervals that govern the epidemiological dynamics of COVID-19 infections. Our results show that the incubation period falls within the range of 2-14 days with 95% confidence and has a mean of around 5 days when approximated using the best-fit lognormal distribution. The mean time from illness onset to hospital admission (for treatment and/or isolation) was estimated at 3-4 days without truncation and at 5-9 days when right truncated. Based on the 95th percentile estimate of the incubation period, we recommend that the length of quarantine should be at least 14 days. The median time delay of 13 days from illness onset to death (17 days with right truncation) should be considered when estimating the COVID-19 case fatality risk.</jats:p>",2020-01-28,"['Natalie M. Linton', 'Tetsuro Kobayashi', 'Yichi Yang', 'Katsuma Hayashi', 'Andrei R. Akhmetzhanov', 'Sung-mok Jung', 'Baoyin Yuan', 'Ryo Kinoshita', 'Hiroshi Nishiura']",,,,True
fdf006a84a946f24f5905dcea8c5c1ee266c26d2,medrxiv,"Epidemiological identification of a novel infectious disease in real time: Analysis of the atypical pneumonia outbreak in Wuhan, China, 2019-20",doi.org/10.1101/2020.01.26.20018887,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: Virological tests indicate that a novel coronavirus is the most likely explanation for the 2019-20 pneumonia outbreak in Wuhan, China. We demonstrate that non-virological descriptive characteristics could have determined that the outbreak is caused by a novel pathogen in advance of virological testing.  Methods: Characteristics of the ongoing outbreak were collected in real time from two medical social media sites. These were compared against characteristics of ten existing pathogens that can induce atypical pneumonia. The probability that the current outbreak is due to ""Disease X"" (i.e., previously unknown etiology) as opposed to one of the known pathogens was inferred, and this estimate was updated as the outbreak continued.  Results: The probability that Disease X is driving the outbreak was assessed as over 32% on 31 December 2019, one week before virus identification. After some specific pathogens were ruled out by laboratory tests on 5 Jan 2020, the inferred probability of Disease X was over 59%.  Conclusions: We showed quantitatively that the emerging outbreak of atypical pneumonia cases is consistent with causation by a novel pathogen. The proposed approach, that uses only routinely-observed non-virological data, can aid ongoing risk assessments even before virological test results become available.  Keywords: Epidemic; Causation; Bayes' theorem; Diagnosis; Prediction; Statistical model</jats:p>",2020-01-28,"['Sung-mok Jung', 'Ryo Kinoshita', 'Robin N. Thompson', 'Katsuma Hayashi', 'Natalie M. Linton', 'Yichi Yang', 'Andrei R. Akhmetzhanov', 'Hiroshi Nishiura']",,,,False
25d49e49a4cb420ec8ed2a703c0ed88d7cd5d0d0,medrxiv,"Epidemiological identification of a novel infectious disease in real time: Analysis of the atypical pneumonia outbreak in Wuhan, China, 2019-20",doi.org/10.1101/2020.01.27.20018952,,,See https://www.medrxiv.org/submit-a-manuscript,,,,,,,False
12fac9aedb1a09a3922a3c084ce4723708e463d6,medrxiv,"The incubation period of 2019-nCoV infections among travellers from Wuhan, China",doi.org/10.1101/2020.01.27.20018986,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Currently, a novel coronavirus 2019-nCoV causes an outbreak of viral pneumonia in Wuhan, China. Little is known about its epidemiological characteristics. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan, we estimate the mean incubation period to be 6.4 (5.6 - 7.7, 95% CI) days, ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values help to inform case definitions for 2019-nCoV and appropriate durations for quarantine.</jats:p>",2020-01-28,"['Jantien A. Backer', 'Don Klinkenberg', 'Jacco Wallinga']",,,,True
30b5c7b8faf95265f67ae59f4686eaf9b2772893,medrxiv,Estimated effectiveness of traveller screening to prevent international spread of 2019 novel coronavirus (2019-nCoV),doi.org/10.1101/2020.01.28.20019224,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Traveller screening is being used to limit further global spread of 2019 novel coronavirus (nCoV) following its recent emergence. Here, we analyze the expected impact of different travel screening programs given remaining uncertainty around the values of key nCoV life history and epidemiological parameters. Even under best-case assumptions, we estimate that screening will miss around half of infected travellers. Breaking down the factors leading to screening successes and failures, we find that most cases missed by screening are fundamentally undetectable, because they have not yet developed symptoms and are unaware they were exposed. These findings emphasize the need for measures to track travellers who become ill after being missed by a travel screening program. We make our model available for interactive use so stakeholders can explore scenarios of interest using the most up-to-date information. We hope these findings contribute to evidence-based policy to combat the spread of nCoV, and to prospective planning to mitigate future emerging pathogens.</jats:p>",2020-01-30,"['Katelyn Gostic', 'Ana C. R. Gomez', 'Riley O. Mummah', 'Adam J. Kucharski', 'James O. Lloyd-Smith']",,,,True
957e71389292e0881dff2bbe0e87fe6bf8b2d381,medrxiv,Risk for Transportation of 2019 Novel Coronavirus (COVID-19) from Wuhan to Cities in China,doi.org/10.1101/2020.01.28.20019299,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>On January 23, 2020, China quarantined Wuhan to contain an emerging coronavirus (COVID-19). We estimated the probability of transportation of COVID-19 from Wuhan to 369 cities in China before the quarantine. The expected risk is &gt;50% in 130 (95% CI 89-190) cities and &gt;99% in the 4 largest metropolitan areas of China.</jats:p>",2020-01-30,"['Zhanwei Du', 'Ling Wang', 'Simon Cauchemez', 'Xiaoke Xu', 'Xianwen Wang', 'Benjamin J Cowling', 'Lauren Ancel Meyers']",,,,True
2afff5fe89a3e3ec270a41c2b929dfeec68d7d50,medrxiv,Real time estimation of the risk of death from novel coronavirus (2019-nCoV) infection: Inference using exported cases,doi.org/10.1101/2020.01.29.20019547,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The exported cases of 2019 novel coronavirus (2019-nCoV) infection who were confirmed in other countries provide a chance to estimate the cumulative incidence and confirmed case fatality risk (cCFR) in China. Knowledge of the cCFR is critical to characterize the severity and understand pandemic potential of 2019-nCoV in the early stage of epidemic. Using the exponential growth rate of the incidence, the present study statistically estimated the cCFR and the basic reproduction number, i.e., the average number of secondary cases generated by a single primary case in a naive population. As of 24 January 2020, with 23 exported cases, and estimating the growth rate from 8 December 2019 (scenario 1) and using the data since growth of exported cases (scenario 2), the cumulative incidence in China was estimated at 5433 cases (95% confidence interval (CI): 3883, 7160) and 17780 cases (95% CI: 9646, 28724), respectively. The latest estimates of the cCFR were 4.6% (95% CI: 3.1-6.6) for scenario 1 and 7.7% (95% CI: 4.9-11.3%) for scenario 2, respectively. The basic reproduction number was estimated to be 2.2 (95% CI: 2.1, 2.3) and 3.7 (95% CI: 3.1, 4.3) for scenarios 1 and 2, respectively. Based on the results, we note that current 2019-nCoV epidemic has a substation potential to cause a pandemic. The proposed approach can provide insights into early risk assessment using only publicly available data.</jats:p>",2020-02-02,"['Sung-mok Jung', 'Andrei R. Akhmetzhanov', 'Katsuma Hayashi', 'Natalie M. Linton', 'Yichi Yang', 'Baoyin Yuan', 'Tetsuro Kobayashi', 'Ryo Kinoshita', 'Hiroshi Nishiura']",,,,True
a6af28a7f0a0d8d1e4d5b06f5ae38412298bbcb4,medrxiv,Direct Measurement of Rates of Asymptomatic Infection and Clinical Care-Seeking for Seasonal Coronavirus,doi.org/10.1101/2020.01.30.20019612,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The pandemic potential of the novel coronavirus (nCoV) that emerged in Wuhan, China, during December 2019 is strongly tied to the number and contagiousness of undocumented human infections. Here we present findings from a proactive longitudinal sampling study of acute viral respiratory infections that documents rates of asymptomatic infection and clinical care seeking for seasonal coronavirus.  We find that the majority of infections are asymptomatic by most symptom definitions and that only 4% of individuals experiencing a seasonal coronavirus infection episode sought medical care for their symptoms.  These numbers indicate that a very high percentage of seasonal coronavirus infections are undocumented and provide a reference for understanding the spread of the emergent nCoV.</jats:p>",2020-02-03,"['Jeffrey Shaman', 'Marta Galanti']",,,,True
de3f8aaa209f08308aacb81b3a6fcd8db3e805de,medrxiv,"Modelling the epidemic trend of the 2019-nCOV outbreak in Hubei Province, China",doi.org/10.1101/2020.01.30.20019828,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>As of 8am 30th January (Beijing Time) 2020, Approximate 8000 cases across the world have been confirmed. It's necessary to simulate epidemic trend of the 2019-nCOV outbreak in Hubei Province, the hardest-hit area. By SEIR simulation, the predicted epidemic peak in Hubei will be within 28th January 2020 to 7th February 2020, up to 7000-9000 infectious cases in total. The estimate above was based on some assumptions and limitations exited.</jats:p>",2020-02-02,['Lizhe Ai'],,,,False
f17c6ac4986aecba2dc22f67b32f2d16b369117b,medrxiv,Transmission and epidemiological characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected Pneumonia (COVID-19): preliminary evidence obtained in comparison with 2003-SARS,doi.org/10.1101/2020.01.30.20019836,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objectives: Latest epidemic data of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected Pneumonia (COVID-19) was collected and a detailed statistical analysis was carried out to make comparison with 2003-SARS in order to provide scientific reference for the prevention and control of COVID-19. Methods: The information of COVID-19 and 2003-SARS from websites of NHCPRC and the World Health Organization was collected, and then the transmission dynamics of the two kinds of infectious diseases were analyzed. The information of 853 confirmed COVID-19 patients obtained from the website of health committees of 18 provinces. A descriptive epidemiological analysis method was employed to carefully analyze the epidemic characteristics. Subsequently, the COVID-19 epidemic data in Wuhan and other inland regions of China was analyzed separately and compared. A multivariate function model was constructed based on the confirmed COVID-19 case data. Results: The growth rate of new cases and deaths of COVID-19 were significantly faster than those of 2003-SARS. The number of confirmed cases in Wuhan and other inland areas both showed increasing trends. 853 confirmed COVID-19 cases aged 1 months to 94 years and the average age was (45.05 ± 17.22) years. The gender ratio (M: F) was 1.12: 1. Conclusions: The fatality rate of COVID-19 is lower than that of 2003-SARS and the cure rate is higher. The age of COVID-19 patients is mainly concentrated in the 30-50 years old (60.61%). The harm of the first-generation COVID-19 patients is higher than that of secondary cases.</jats:p>",2020-02-02,"['Rongqiang Zhang', 'Hui Liu', 'Fengying Li', 'Bei Zhang', 'Qiling Liu', 'Xiangwen Li', 'Limei Luo']",,,,True
261df5b4f76de3cb7aa2e8dbeac321221f065df1,medrxiv,The impact of transmission control measures during the first 50 days of the COVID-19 epidemic in China,doi.org/10.1101/2020.01.30.20019844,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Respiratory illness caused by a novel coronavirus (COVID-19) appeared in China during December 2019. Attempting to contain infection, China banned travel to and from Wuhan city on 23 January and implemented a national emergency response. Here we evaluate the spread and control of the epidemic based on a unique synthesis of data including case reports, human movement and public health interventions. The Wuhan shutdown slowed the dispersal of infection to other cities by an estimated 2.91 days (95%CI: 2.54-3.29), delaying epidemic growth elsewhere in China. Other cities that implemented control measures pre-emptively reported 33.3% (11.1-44.4%) fewer cases in the first week of their outbreaks (13.0; 7.1-18.8) compared with cities that started control later (20.6; 14.5-26.8). Among interventions investigated here, the most effective were suspending intra-city public transport, closing entertainment venues and banning public gatherings. The national emergency response delayed the growth and limited the size of the COVID-19 epidemic and, by 19 February (day 50), had averted hundreds of thousands of cases across China.</jats:p>",2020-02-02,"['Huaiyu Tian', 'Yonghong Liu', 'Yidan Li', 'Chieh-Hsi Wu', 'Bin Chen', 'Moritz U. G. Kraemer', 'Bingying Li', 'Jun Cai', 'Bo Xu', 'Qiqi Yang', 'Ben Wang', 'Peng Yang', 'Yujun Cui', 'Yimeng Song', 'Pai Zheng', 'Quanyi Wang', 'Ottar N Bjornstad', 'Ruifu Yang', 'Bryan Grenfell', 'Oliver Pybus', 'Christopher Dye']",,,,False
0ff4ad5359ee2df3568605385a8616d8da66bf2c,medrxiv,Reconciling early-outbreak estimates of the basic reproductive number and its uncertainty: framework and applications to the novel coronavirus (SARS-CoV-2) outbreak,doi.org/10.1101/2020.01.30.20019877,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>A novel coronavirus (SARS-CoV-2) has recently emerged as a global threat. As the epidemic progresses, many disease modelers have focused on estimating the basic reproductive number Ro -- the average number of secondary cases caused by a primary case in an otherwise susceptible population. The modeling approaches and resulting estimates of Ro vary widely, despite relying on similar data sources. Here, we present a novel statistical framework for comparing and combining different estimates of Ro across a wide range of models by decomposing the basic reproductive number into three key quantities: the exponential growth rate $r$, the mean generation interval $\bar G$, and the generation-interval dispersion $\kappa$. We then apply our framework to early estimates of Ro for the SARS-CoV-2 outbreak. We show that many early Ro estimates are overly confident. Our results emphasize the importance of propagating uncertainties in all components of Ro, including the shape of the generation-interval distribution, in efforts to estimate Ro at the outset of an epidemic.</jats:p>",2020-02-02,"['Sang Woo Park', 'Benjamin M. Bolker', 'David Champredon', 'David J.D. Earn', 'Michael Li', 'Joshua S. Weitz', 'Bryan T. Grenfell', 'Jonathan Dushoff']",,,,True
a01672035e0b9d21f9a934b9c9071610513325f2,medrxiv,Effectiveness of airport screening at detecting travellers infected with 2019-nCoV,doi.org/10.1101/2020.01.31.20019265,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>As the number of novel coronavirus cases grows both inside and outside of China, public health authorities require evidence on the effectiveness of control measures such as thermal screening of arrivals at airports. We evaluated the effectiveness of exit and entry screening for 2019-nCoV infection. In our baseline scenario, we estimated that 46.5% (95%CI: 35.9 to 57.7) of infected travellers would not be detected, depending on the incubation period, sensitivity of exit and entry screening, and the proportion of cases which are asymptomatic. Airport screening is unlikely to detect a sufficient proportion of 2019-nCoV infected travellers to avoid entry of infected travellers. We developed an online tool so that results can be updated as new information becomes available.</jats:p>",2020-02-02,"['Billy Quilty', 'Sam Clifford', 'Stefan Flasche', 'Rosalind M Eggo']",,,,True
a44334e676e43c1889d282b0f0a8365f0f1e0c52,medrxiv,Early dynamics of transmission and control of COVID-19: a mathematical modelling study,doi.org/10.1101/2020.01.31.20019901,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: An outbreak of the novel coronavirus SARS-CoV-2 has led to 46,997 confirmed cases as of 13th February 2020. Understanding the early transmission dynamics of the infection and evaluating the effectiveness of control measures is crucial for assessing the potential for sustained transmission to occur in new areas.   Methods: We combined a stochastic transmission model with data on cases of novel coronavirus disease (COVID-19) in Wuhan and international cases that originated in Wuhan to estimate how transmission had varied over time during January and February 2020. Based on these estimates, we then calculated the probability that newly introduced cases might generate outbreaks in other areas.   Findings: We estimated that the median daily reproduction number, Rt , declined from 2.35 (95% CI: 1.15-4.77) one week before travel restrictions were introduced on 23rd January to 1.05 (95% CI: 0.413-2.39) one week after. Based on our estimates of Rt,we calculated that in locations with similar transmission potential as Wuhan in early January, once there are at least four independently introduced cases, there is a more than 50% chance the infection will establish within that population.   Interpretation: Our results show that COVID-19 transmission likely declined in Wuhan during late January 2020, coinciding with the introduction of control measures. As more cases arrive in international locations with similar transmission potential to Wuhan pre-control, it is likely many chains of transmission will fail to establish initially, but may still cause new outbreaks eventually.</jats:p>",2020-02-02,,,,,True
898880683d9a962428033fd7500f74647c4a36f0,medrxiv,Early epidemiological analysis of the 2019-nCoV outbreak based on a crowdsourced data,doi.org/10.1101/2020.01.31.20019935,,,See https://www.medrxiv.org/submit-a-manuscript,,,,,,,True
97e0830fe6c8bf6facb896320dd1b8d31ab49a54,medrxiv,Estimating the risk on outbreak spreading of 2019-nCoV in China using transportation data,doi.org/10.1101/2020.02.01.20019984,,,See https://www.medrxiv.org/submit-a-manuscript,,,,,,,True
7b40dfdf9a60cfe4a199cb967ee458b7dfaabe0c,medrxiv,The incubation period of 2019-nCoV from publicly reported confirmed cases: estimation and application,doi.org/10.1101/2020.02.02.20020016,,,See https://www.medrxiv.org/submit-a-manuscript,,,,,,,True
3990e8112c87103e73c37a3f89155b3e53326fd4,medrxiv,Evidence and characteristics of human-to-human transmission of SARS-CoV-2,doi.org/10.1101/2020.02.03.20019141,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: On December 31, 2019, an outbreak of COVID-19 in humans was reported in Wuhan, and then spread fast to other provinces, China. We analyzed data from field investigations and genetic sequencing to describe the evidence and characteristics of human-to-human transmission in Guangdong Province. Methods: A confirmed COVID-19 case was defined if a suspected case was verified with positive of SARS-CoV-2 in throat swabs, nasal swabs, bronchoalveolar lavage fluid (BALF), or endotracheal aspirates by real-time reverse transcriptase polymerase chain reaction assay (RT-PCR) or genetic sequencing. Field investigations were conducted for each confirmed case. Clinical and demographic data of confirmed cases were collected from medical records. Exposure and travel history were obtained by interview. Results: A total of 1,151 confirmed cases were identified as of February 10, 2020 in Guangdong Province, China. Of them, 697 (60.1%) cases were from 234 cluster infections. Two hundred and fourteen (18.6%) were secondary cases, in which 144 cases were from family cluster infections. With the epidemic continuing, although familial cluster events were dominated, community cluster events increased with a nosocomial event. The whole genomes within the same family cluster infections were identical, and presented a few unique single nucleotide variants (SNVs) compared with SARS-CoV-2 identified on December 2019 in Wuhan. Conclusions: We observed evident human-to-human transmissions of SARS-CoV-2 in Guangdong, China. Although most of them were from family cluster infections, community and nosocomial infections were increasing. Our findings indicate that human-to-human transmission risks are transferring from family to community in Guangdong Province.</jats:p>",2020-02-05,"['Min Kang', 'Jie Wu', 'Wenjun Ma', 'Jianfeng He', 'Jing Lu', 'Tao Liu', 'Baisheng Li', 'Shujiang Mei', 'Feng Ruan', 'Lifeng Lin', 'Lirong Zou', 'Changwen Ke', 'Haojie Zhong', 'Yingtao Zhang', 'Xuguang Chen', 'Zhe Liu', 'Qi Zhu', 'Jianpeng Xiao', 'Jianxiang Yu', 'Jianxiong Hu', 'Weilin Zeng', 'Xing Li', 'Yuhuang Liao', 'Xiujuan Tang', 'Songjian Xiao', 'Ying Wang', 'Yingchao Song', 'Xue Zhuang', 'Lijun Liang', 'Siqing Zeng', 'Guanhao He', 'Peng Lin', 'Huihong Deng', 'Tie Song']",,,,False
a1bff76ce360e8990b0a4ee2a5228a6e6e63d9c1,medrxiv,Serial interval of novel coronavirus (2019-nCoV) infections,doi.org/10.1101/2020.02.03.20019497,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: To estimate the serial interval of novel coronavirus (COVID-19) from information on 28 infector-infectee pairs. Methods: We collected dates of illness onset for primary cases (infectors) and secondary cases (infectees) from published research articles and case investigation reports. We subjectively ranked the credibility of the data and performed analyses on both the full dataset (n=28) and a subset of pairs with highest certainty in reporting (n=18). In addition, we adjusting for right truncation of the data as the epidemic is still in its growth phase. Results: Accounting for right truncation and analyzing all pairs, we estimated the median serial interval at 4.0 days (95% credible interval [CrI]: 3.1, 4.9). Limiting our data to only the most certain pairs, the median serial interval was estimated at 4.6 days (95% CrI: 3.5, 5.9). Conclusions: The serial interval of COVID-19 is shorter than its median incubation period. This suggests that a substantial proportion of secondary transmission may occur prior to illness onset. The COVID-19 serial interval is also shorter than the serial interval of severe acute respiratory syndrome (SARS), indicating that calculations made using the SARS serial interval may introduce bias.</jats:p>",2020-02-13,"['Hiroshi Nishiura', 'Natalie M Linton', 'Andrei R. Akhmetzhanov']",,,,True
5d3612cd95331a2f0c43ef9d03ce583b5ff8c995,medrxiv,Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of 2019-nCoV,doi.org/10.1101/2020.02.03.20020206,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The 2019-nCoV is reported to share the same entry (ACE2) as SARS-CoV according to the updated findings. Analyzing the distribution and expression level of the route of coronavirus may help reveal underlying mechanisms of viral susceptibility and post-infection modulation. In this study, we found that the expression of ACE2 in healthy populations and patients with underlying diseases was not significantly different, suggesting relatively similar susceptibility, which was consistent with current clinical observations. Moreover, based on the expression of ACE2 in smoking individuals, we inferred that long-term smoking might be a risk factor for 2019-nCoV. Analyzing the ACE2 in SARS-CoV infected cells suggested that ACE2 was more than just a receptor but also participated in post-infection regulation, including immune response, cytokine secretion, and viral genome replication. We also constructed Protein-protein interaction (PPI) networks and identified hub genes in viral activity and cytokine secretion. Our findings could explain the clinical symptoms so far and help clinicians and researchers understand the pathogenesis and design therapeutic strategies for 2019-nCoV.</jats:p>",2020-02-05,"['Xiang He', 'Lei Zhang', 'Qin Ran', 'Anying Xiong', 'Junyi Wang', 'Dehong Wu', 'Feng Chen', 'Guoping Li']",,,,True
b0c409979750e2975f6c707cf4a9a44ee6c9e748,medrxiv,Estimation of the asymptomatic ratio of novel coronavirus infections (COVID-19),doi.org/10.1101/2020.02.03.20020248,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>A total of 565 Japanese citizens were evacuated from Wuhan, China to Japan. All passengers were screened for symptoms and also undertook reverse transcription polymerase chain reaction testing, identifying 5 asymptomatic and 7 symptomatic passengers testing positive for 2019-nCoV. We show that the screening result is suggestive of the asymptomatic ratio at 41.6%.</jats:p>",2020-02-11,"['Hiroshi Nishiura', 'Tetsuro Kobayashi', 'Takeshi Miyama', 'Ayako Suzuki', 'Sungmok Jung', 'Katsuma Hayashi', 'Ryo Kinoshita', 'Yichi Yang', 'Baoyin Yuan', 'Andrei R. Akhmetzhanov', 'Natalie M Linton']",,,,False
21100aba41a4bfb48d7dc37f1bf5dbb38bf3867a,medrxiv,Network-based Drug Repurposing for Human Coronavirus,doi.org/10.1101/2020.02.03.20020263,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Human Coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle east respiratory syndrome coronavirus (MERS-CoV), and 2019 novel coronavirus (2019-nCoV), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV. Drug repurposing, represented as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV-host interactome and drug targets in the human protein-protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV has the highest nucleotide sequence identity with SARS-CoV (79.7%) among the six other known pathogenic HCoVs. Specifically, the envelope and nucleocapsid proteins of 2019-nCoV are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and known HCoV-host interactions in the human protein-protein interactome, we computationally identified 135 putative repurposable drugs for the potential prevention and treatment of HCoVs. In addition, we prioritized 16 potential anti-HCoV repurposable drugs (including melatonin, mercaptopurine, and sirolimus) that were further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. Finally, we showcased three potential drug combinations (including sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the Complementary Exposure pattern: the targets of the drugs both hit the HCoV-host subnetwork, but target separate neighborhoods in the human protein-protein interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations toward future clinical trials for HCoVs.</jats:p>",2020-02-05,"['Yadi Zhou', 'Yuan Hou', 'Jiayu Shen', 'Yin Huang', 'William Martin', 'Feixiong Cheng']",,,,True
5c525cc04075b7c82e52b1e80d96bb394b1a0907,medrxiv,Getting to zero quickly in the 2019-nCov epidemic with vaccines or rapid testing,doi.org/10.1101/2020.02.03.20020271,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Any plan for stopping the ongoing 2019-nCov epidemic must be based on a quantitative understanding of the proportion of the at-risk population that needs to be protected by effective control measures in order for transmission to decline sufficiently and quickly enough for the epidemic to end. Using an SEIR-type transmission model, we contrasted two alternate strategies by modeling the proportion of the population that needs to be protected from infection by one-time vaccination (assuming 100% effectiveness) or by testing with isolation and treatment of individuals within six, 24, or 48 hours of symptom onset. If R is currently 2.2, vaccination at the herd immunity coverage of 55% would drive R just below 1, but transmission could persist for years. Over 80% of coverage is required to end the epidemic in 6 months with population-wide vaccination. The epidemic could be ended in just under a year if testing with isolation and treatment reached 80% of symptomatically infected patients within 24 hours of symptom onset (assuming 10% asymptomatic transmission). The epidemic could be ended in six months if testing with isolation and treatment reached 90% of symptomatic patients. If 90% of symptomatic patients could be tested within six hours of symptoms appearing, the epidemic could be ended in under four months.</jats:p>",2020-02-05,"['Gerardo Chowell', 'Ranu Dhillon', 'Devabhaktuni Srikrishna']",,,,True
b51d1c7287ac75790a52752489577d33d522898b,medrxiv,Diarrhea may be underestimated: a missing link in 2019 novel coronavirus,doi.org/10.1101/2020.02.03.20020289,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The outbreak of pneumonia caused by the 2019 Novel Coronavirus (2019-nCoV) was reported in Wuhan City, China. However, the clinical symptoms varied in different reports. Based on the results of inter-group difference test, we found that the incidence of diarrhea differed in three recent reports. As 2019-nCoV utilizes the same cell entry receptor ACE2 as severe acute respiratory syndrome coronavirus (SARS-CoV) and ACE2 tightly controls intestinal inflammation, to trace the route of infection mediated by 2019-nCoV, we used the single-cell RNA sequencing data for analysis. We found that the ACE2 mRNA was highly expressed in the healthy human small intestine rather than the lung. Besides, single-cell RNA sequencing data showed that ACE2 was significantly elevated in the proximal and distal enterocytes, where the small intestinal epithelium is exposed to the foreign pathogen. Thus, we suspect that ACE2-expressing small intestinal epithelium cells might be vulnerable to 2019-nCoV infection when people eat infected wild animals and diarrhea may serve as an indicator for infection, suggesting that clinicians should pay more attention to patients with diarrhea during the outbreak of pneumonia.</jats:p>",2020-02-11,"['Weicheng Liang', 'Zhijie Feng', 'Shitao Rao', 'Cuicui Xiao', 'Zexiao Lin', 'Qi Zhang', 'Wei Qi']",,,,True
1b531d266b4933bf8040739ed199914655b075d6,medrxiv,"Population movement, city closure and spatial transmission of the 2019-nCoV infection in China",doi.org/10.1101/2020.02.04.20020339,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The outbreak of pneumonia caused by a novel coronavirus (2019-nCoV) in Wuhan City of China obtained global concern, the population outflow from Wuhan has contributed to spatial expansion in other parts of China. We examined the effects of population outflow from Wuhan on the 2019-nCoV transmission in other provinces and cities of China, as well as the impacts of the city closure in Wuhan. We observed a significantly positive association between population movement and the number of cases. Further analysis revealed that if the city closure policy was implemented two days earlier, 1420 (95% CI: 1059, 1833) cases could be prevented, and if two days later, 1462 (95% CI: 1090, 1886) more cases would be possible. Our findings suggest that population movement might be one important trigger of the 2019-nCoV infection transmission in China, and the policy of city closure is effective to prevent the epidemic.</jats:p>",2020-02-05,"['Siqi Ai', 'Guanghu Zhu', 'Fei Tian', 'Huan Li', 'Yuan Gao', 'Yinglin Wu', 'Qiyong Liu', 'Hualiang Lin']",,,,True
e3f19f88e7e3d1279b4d93e4db041e44a8d35dbb,medrxiv,"Epidemiological parameter review and comparative dynamics of influenza, respiratory syncytial virus, rhinovirus, human coronavirus, and adenovirus",doi.org/10.1101/2020.02.04.20020404,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Influenza-like illness (ILI) accounts for a large burden of annual morbidity and mortality worldwide. A finer-grained knowledge of the parameters and dynamics of the viruses commonly underlying ILI is needed for modeling, diagnostic, and intervention efforts. We conducted an extensive literature review for epidemiological parameter values for influenza, respiratory syncytial virus (RSV), rhinovirus, human coronavirus (HCoV), and adenovirus. We also developed a deterministic SEIR model for ILI, and derived an expression for R0. We here report ranges and means for parameters for these five common viruses.</jats:p>",2020-02-05,"['Julie Spencer', 'Deborah P Shutt', 'Sarah K Moser', 'Hannah Clegg', 'Helen J Wearing', 'Harshini Mukundan', 'Carrie A Manore']",,,,True
c9533866dd77deaa65ee1015b57bca5486f93326,medrxiv,The impact of traffic isolation in Wuhan on the spread of 2019-nCov,doi.org/10.1101/2020.02.04.20020438,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The 2019-nCoV outbreak occurred near the Chinese Spring Festival transport period in Wuhan. As an important transportation center, the migration of Wuhan accelerated the spread of 2019-nCoV across mainland China. Based on the cumulative Baidu migration index (CBMI), we first analyzed the proportion of Wuhan's migrant population to other cities. Our results confirm that there is a significant correlation between the export population of Wuhan and reported cases in various regions. We subsequently found that the mortality rate in Hubei Province was much higher than that in other regions of mainland China, while the investigation of potential cases in Wuhan was far behind other provinces in Mainland China, which indicates the effectiveness of early isolation.</jats:p>",2020-02-05,"['Gehui Jin', 'Jiayu Yu', 'Liyuan Han', 'Shiwei Duan']",,,,True
164b0678afc42f1923aa100b624ca969a53fb3b2,medrxiv,"Forecasting the Wuhan coronavirus (2019-nCoV) epidemics using a simple (simplistic) model - update (Feb. 8, 2020)",doi.org/10.1101/2020.02.04.20020461,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Confirmed infection cases in mainland China were analyzed using the data up to January 28, 2020 (first 13 days of reliable confirmed cases). For the first period the cumulative number of cases followed an exponential function. However, from January 28, we discerned a downward deviation from the exponential growth. This slower-than-exponential growth was also confirmed by a steady decline of the effective reproduction number. A backtrend analysis suggested the original basic reproduction number R0 to be about 2.4 to 2.5. As data become available, we subsequently analyzed them during three consecutive periods obtaining a sequence of model predictions. All available data up were processed the same way. We used a simple logistic growth model that fitted very well with all data. Using this model and the three sets of data, we estimated maximum cases as about 21,000, 28,000 and 35,000 cases refining these predictions in near-real time. With slightly different approach (linearization in time) the estimate of maximum cases was even higher (about 65,000).  Although the estimates of maximum cases increase as more data were reported all models show reaching a peak in mid-February in contrast to the unconfined exponential growth. These predictions do not account for any possible other secondary sources of infection.</jats:p>",2020-02-05,['Slav W Hermanowicz'],,,,True
013d9d1cba8a54d5d3718c229b812d7cf91b6c89,medrxiv,"Assessing spread risk of Wuhan novel coronavirus within and beyond China, January-April 2020: a travel network-based modelling study",doi.org/10.1101/2020.02.04.20020479,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: A novel coronavirus (2019-nCoV) emerged in Wuhan City, China, at the end of 2019 and has caused an outbreak of human-to-human transmission with a Public Health Emergency of International Concern declared by the World Health Organization on January 30, 2020. Aim: We aimed to estimate the potential risk and geographic range of Wuhan novel coronavirus (2019-nCoV) spread within and beyond China from January through to April, 2020. Methods: A series of domestic and international travel network-based connectivity and risk analyses were performed, by using de-identified and aggregated mobile phone data, air passenger itinerary data, and case reports. Results: The cordon sanitaire of Wuhan is likely to have occurred during the latter stages of peak population numbers leaving the city before Lunar New Year (LNY), with travellers departing into neighbouring cities and other megacities in China. We estimated that 59,912 air passengers, of which 834 (95% UI: 478 - 1349) had 2019-nCoV infection, travelled from Wuhan to 382 cities outside of mainland China during the two weeks prior to the lockdown of Wuhan. The majority of these cities were in Asia, but major hubs in Europe, the US and Australia were also prominent, with strong correlation seen between predicted importation risks and reported cases. Because significant spread has already occurred, a large number of airline travellers (3.3 million under the scenario of 75% travel reduction from normal volumes) may be required to be screened at origin high-risk cities in China and destinations across the globe for the following three months of February to April, 2020 to effectively limit spread beyond its current extent. Conclusion: Further spread of 2019-nCoV within China and international exportation is likely to occur. All countries, especially vulnerable regions, should be prepared for efforts to contain the 2019-nCoV infection.</jats:p>",2020-02-05,"['Shengjie Lai', 'Isaac Bogoch', 'Nick Ruktanonchai', 'Alexander Watts', 'Xin Lu', 'Weizhong Yang', 'Hongjie Yu', 'Kamran Khan', 'Andrew J Tatem']",,,,True
158e546658e42ab0a89d174bc9facb437a034df6,medrxiv,Using predicted imports of 2019-nCoV cases to determine locations that may not be identifying all imported cases,doi.org/10.1101/2020.02.04.20020495,,,See https://www.medrxiv.org/submit-a-manuscript,<jats:p>Cases from the ongoing outbreak of atypical pneumonia caused by the 2019 novel coronavirus (2019-nCoV) exported from mainland China can lead to self-sustained outbreaks in other populations. Internationally imported cases are currently being reported in several different locations. Early detection of imported cases is critical for containment of the virus. Based on air travel volume estimates from Wuhan to international destinations and using a generalized linear regression model we identify locations which may potentially have undetected internationally imported cases.</jats:p>,2020-02-05,"['Pablo M De Salazar', 'Rene Niehus', 'Aimee Taylor', 'Caroline O Buckee', 'Marc Lipsitch']",,,,True
136ee862ad53b606c8f2bea917b9705f5079e88e,medrxiv,Risk assessment of novel coronavirus COVID-19 outbreaks outside China,doi.org/10.1101/2020.02.04.20020503,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>We developed a computational tool to assess the risk of novel coronavirus outbreaks outside China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as:  (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions,  and the efficacy of entry screening at destination; (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number Rloc). We found that in countries with low connectivity to China but with relatively high Rloc, the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low Rloc benefit the most from policies that further reduce Rloc. Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia and Europe, and we investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing.</jats:p>",2020-02-05,"['Peter Boldog', 'Tamas Tekeli', 'Zsolt Vizi', 'Attila Denes', 'Ferenc Bartha', 'Gergely Rost']",,,,True
59eab95c43fdea01481fdbf9bae45dfe28ffc693,medrxiv,"Bulk and single-cell transcriptomics identify tobacco-use disparity in lung gene expression of ACE2, the receptor of 2019-nCov",doi.org/10.1101/2020.02.05.20020107,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>In current severe global emergency situation of 2019-nCov outbreak, it is imperative to identify vulnerable and susceptible groups for effective protection and care. Recently, studies found that 2019-nCov and SARS-nCov share the same receptor, ACE2. In this study, we analyzed five large-scale bulk transcriptomic datasets of normal lung tissue and two single-cell transcriptomic datasets to investigate the disparities related to race, age, gender and smoking status in ACE2 gene expression and its distribution among cell types. We didn't find significant disparities in ACE2 gene expression between racial groups (Asian vs Caucasian), age groups (&gt;60 vs &lt;60) or gender groups (male vs female). However, we observed significantly higher ACE2 gene expression in former smoker's lung compared to non-smoker's lung. Also, we found higher ACE2 gene expression in Asian current smokers compared to non-smokers but not in Caucasian current smokers, which may indicate an existence of gene-smoking interaction. In addition, we found that ACE2 gene is expressed in specific cell types related to smoking history and location. In bronchial epithelium, ACE2 is actively expressed in goblet cells of current smokers and club cells of non-smokers. In alveoli, ACE2 is actively expressed in remodelled AT2 cells of former smokers. Together, this study indicates that smokers especially former smokers may be more susceptible to 2019-nCov and have infection paths different with non-smokers. Thus, smoking history may provide valuable information in identifying susceptible population and standardizing treatment regimen.</jats:p>",2020-02-11,['Guoshuai Cai'],,,,True
f5d9ab798adf8face1655d476644ebb75fbfef18,medrxiv,"ACE2 expression by colonic epithelial cells is associated with viral infection, immunity and energy metabolism",doi.org/10.1101/2020.02.05.20020545,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Respiratory disease caused by the 2019 novel coronavirus (2019-nCoV) pneumonia first emerged in Wuhan, Hubei Province, China, in December 2019 and spread rapidly to other provinces and other countries. Angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV and has been suggested to be also the receptor for 2019-nCoV. Paradoxically, ACE2 expression in the lung protects mice from SARS-CoV spike protein induced lung injury by attenuating the renin-angiotensin system. In the intestine, ACE2 also suppresses intestinal inflammation by maintaining amino acid homeostasis, antimicrobial peptide expression and ecology of the gut microbiome. Upon analysis of single cell-RNA sequencing data from control subjects and those with colitis or inflammatory bowel disease (IBD), we found that ACE2 expression in the colonocytes was positively associated with genes regulating viral infection, innate and cellular immunity, but was negatively associated with viral transcription, protein translation, humoral immunity, phagocytosis and complement activation. In summary, we suggest that ACE2 may play dual roles in mediating the susceptibility and immunity of 2019-nCoV infection.</jats:p>",2020-02-07,"['Jun Wang', 'Shanmeizi Zhao', 'Ming Liu', 'Zhiyao Zhao', 'Yiping Xu', 'Ping Wang', 'Meng Lin', 'Yanhui Xu', 'Bing Huang', 'Xiaoyu Zuo', 'Zhanghua Chen', 'Fan Bai', 'Jun Cui', 'Andrew M Lew', 'Jincun Zhao', 'Yan Zhang', 'Haibin Luo', 'Yuxia Zhang']",,,,True
5f6a410a4ba086b296100a8a5a10df59eb337c90,medrxiv,Epidemic doubling time of the COVID-19 epidemic by Chinese province,doi.org/10.1101/2020.02.05.20020750,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>COVID-19 epidemic doubling time by Chinese province was increasing from January 20 through February 9, 2020. Yet, the harmonic mean doubling time was relatively short, ranging from 1.4 (Hunan, 95% CI, 1.2-2.0) to 3.0 (Xinjiang, 95% CI, 2.0-4.9) days, with an estimate of 2.5 days (95% CI, 2.4-2.7) for Hubei.</jats:p>",2020-02-06,"['Kamalich Muniz-Rodriguez', 'Gerardo Chowell', 'Chi-Hin Cheung', 'Dongyu Jia', 'Po-Ying Lai', 'Yiseul Lee', 'Manyun Liu', 'Sylvia K. Ofori', 'Kimberlyn M. Roosa', 'Lone Simonsen', 'Cecile G. Viboud', 'Isaac Chun-Hai Fung']",,,,True
8762adc9311e5803d1de438493772269acfe7fa3,medrxiv,Preparedness and vulnerability of African countries against introductions of 2019-nCoV,doi.org/10.1101/2020.02.05.20020792,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The novel coronavirus (2019-nCoV) epidemic has spread to 23 countries from China. Local cycles of transmission already occurred in 7 countries following case importation. No African country has reported cases yet. The management and control of 2019-nCoV introductions heavily relies on the public health capacity of a country. Here we evaluate the preparedness and vulnerability of African countries against their risk of importation of 2019-nCoV. We used data on air travel volumes departing from airports in the infected provinces in China and directed to Africa to estimate the risk of introduction per country. We determined the countries capacity to detect and respond to cases with two indicators: preparedness, using the WHO International Health Regulation Monitoring and Evaluation Framework; and vulnerability, with the Infectious Disease Vulnerability Index. Countries were clustered according to the Chinese regions contributing the most to their risk.  Findings: Countries at the highest importation risk (Egypt, Algeria, Republic of South Africa) have moderate to high capacity to respond to outbreaks. Countries at moderate risk (Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, Kenya) have variable capacity and high vulnerability. Three clusters of countries are identified that share the same exposure to the risk originating from the provinces of Guangdong, Fujian, and Beijing, respectively.  Interpretation: Several countries in Africa are stepping up their preparedness to detect and cope with 2019-nCoV importations. Resources and intensified surveillance and capacity capacity should be urgently prioritized towards countries at moderate risk that may be ill-prepared to face the importation and to limit onward transmission.</jats:p>",2020-02-07,"['Marius Gilbert', 'Giulia Pullano', 'Francesco Pinotti', 'Eugenio Valdano', 'Chiara Poletto', 'Pierre-Yves Boelle', ""Eric D'Ortenzio"", 'Yazdan Yazdanpanah', 'Serge Paul Eholie', 'Mathias Altmann', 'Bernardo Gutierrez', 'Moritz U. G. Kraemer', 'Vittoria Colizza']",,,,True
c85f571a674c7fed0ccb9176e9cf9f3d3659ca32,medrxiv,Analysis of the epidemic growth of the early 2019-nCoV outbreak using internationally confirmed cases,doi.org/10.1101/2020.02.06.20020941,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: On January 23, 2020, a quarantine was imposed on travel in and out of Wuhan, where the 2019 novel coronavirus (2019-nCoV) outbreak originated from. Previous analyses estimated the basic epidemiological parameters using symptom onset dates of the confirmed cases in Wuhan and outside China.  Methods: We obtained information on the 46 coronavirus cases who traveled from Wuhan before January 23 and have been subsequently confirmed in Hong Kong, Japan, Korea, Macau, Singapore, and Taiwan as of February 5, 2020. Most cases have detailed travel history and disease progress. Compared to previous analyses, an important distinction is that we used this data to informatively simulate the infection time of each case using the symptom onset time, previously reported incubation interval, and travel history. We then fitted a simple exponential growth model with adjustment for the January 23 travel ban to the distribution of the simulated infection time. We used a Bayesian analysis with diffuse priors to quantify the uncertainty of the estimated epidemiological parameters. We performed sensitivity analysis to different choices of incubation interval and the hyperparameters in the prior specification.  Results: We found that our model provides good fit to the distribution of the infection time. Assuming the travel rate to the selected countries and regions is constant over the study period, we found that the epidemic was doubling in size every 2.9 days (95% credible interval [CrI], 2 days--4.1 days). Using previously reported serial interval for 2019-nCoV, the estimated basic reproduction number is 5.7 (95% CrI, 3.4--9.2). The estimates did not change substantially if we assumed the travel rate doubled in the last 3 days before January 23, when we used previously reported incubation interval for severe acute respiratory syndrome (SARS), or when we changed the hyperparameters in our prior specification.  Conclusions: Our estimated epidemiological parameters are higher than an earlier report using confirmed cases in Wuhan. This indicates the 2019-nCoV could have been spreading faster than previous estimates.</jats:p>",2020-02-09,"['Qingyuan Zhao', 'Yang Chen', 'Dylan S Small']",,,,True
dfb0fedbeed56bd2b795a67faab28295afc14c96,medrxiv,Clinical characteristics of 2019 novel coronavirus infection in China,doi.org/10.1101/2020.02.06.20020974,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Since December 2019, acute respiratory disease (ARD) due to 2019 novel coronavirus (2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. We sought to delineate the clinical characteristics of these cases. Methods: We extracted the data on 1,099 patients with laboratory-confirmed 2019-nCoV ARD from 552 hospitals in 31 provinces/provincial municipalities through January 29th, 2020. Results: The median age was 47.0 years, and 41.90% were females. Only 1.18% of patients had a direct contact with wildlife, whereas 31.30% had been to Wuhan and 71.80% had contacted with people from Wuhan. Fever (87.9%) and cough (67.7%) were the most common symptoms. Diarrhea is uncommon. The median incubation period was 3.0 days (range, 0 to 24.0 days). On admission, ground-glass opacity was the typical radiological finding on chest computed tomography (50.00%). Significantly more severe cases were diagnosed by symptoms plus reverse-transcriptase polymerase-chain-reaction without abnormal radiological findings than non-severe cases (23.87% vs. 5.20%, P&lt;0.001). Lymphopenia was observed in 82.1% of patients. 55 patients (5.00%) were admitted to intensive care unit and 15 (1.36%) succumbed. Severe pneumonia was independently associated with either the admission to intensive care unit, mechanical ventilation, or death in multivariate competing-risk model (sub-distribution hazards ratio, 9.80; 95% confidence interval, 4.06 to 23.67). Conclusions: The 2019-nCoV epidemic spreads rapidly by human-to-human transmission. Normal radiologic findings are present among some patients with 2019-nCoV infection. The disease severity (including oxygen saturation, respiratory rate, blood leukocyte/lymphocyte count and chest X-ray/CT manifestations) predict poor clinical outcomes.</jats:p>",2020-02-09,"['Wei-jie Guan', 'Zheng-yi Ni', 'Yu Hu', 'Wen-hua Liang', 'Chun-quan Ou', 'Jian-xing He', 'Lei Liu', 'Hong Shan', 'Chun-liang Lei', 'David SC Hui', 'Bin Du', 'Lan-juan Li', 'Guang Zeng', 'Kowk-Yung Yuen', 'Ru-chong Chen', 'Chun-li Tang', 'Tao Wang', 'Ping-yan Chen', 'Jie Xiang', 'Shi-yue Li', 'Jin-lin Wang', 'Zi-jing Liang', 'Yi-xiang Peng', 'Li Wei', 'Yong Liu', 'Ya-hua Hu', 'Peng Peng', 'Jian-ming Wang', 'Ji-yang Liu', 'Zhong Chen', 'Gang Li', 'Zhi-jian Zheng', 'Shao-qin Qiu', 'Jie Luo', 'Chang-jiang Ye', 'Shao-yong Zhu', 'Nan-shan Zhong']",,,,True
ac35eeb6eaaf382fe0e123719f7dc409046e5d87,medrxiv,Incorporating Human Movement Data to Improve Epidemiological Estimates for 2019-nCoV,doi.org/10.1101/2020.02.07.20021071,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Estimating the key epidemiological features of the novel coronavirus (2019-nCoV) epidemic proves to be challenging, given incompleteness and delays in early data reporting, in particular, the severe under-reporting bias in the epicenter, Wuhan, Hubei Province, China. As a result, the current literature reports widely varying estimates. We developed an alternative geo-stratified debiasing estimation framework by incorporating human mobility with case reporting data in three stratified zones, i.e., Wuhan, Hubei Province excluding Wuhan, and mainland China excluding Hubei. We estimated the latent infection ratio to be around 0.12% (18,556 people) and the basic reproduction number to be 3.24 in Wuhan before the city's lockdown on January 23, 2020. The findings based on this debiasing framework have important implications to prioritization of control and prevention efforts.</jats:p>",2020-02-09,"['Zhidong Cao', 'Qingpeng Zhang', 'Xin Lu', 'Dirk Pfeiffer', 'Lei Wang', 'Hongbing Song', 'Tao Pei', 'Zhongwei Jia', 'Daniel Dajun Zeng']",,,,True
d5f14e63b86239f491c9dd1749cff01dc4d633cb,medrxiv,Networks of information token recurrences derived from genomic sequences may reveal hidden patterns in epidemic outbreaks: A case study of the 2019-nCoV coronavirus.,doi.org/10.1101/2020.02.07.20021139,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Profiling the genetic evolution and dynamic spreading of viruses is a crucial task when responding to epidemic outbreaks. We aim to devise novel ways to model, visualise and analyse the temporal dynamics of epidemic outbreaks in order to help researchers and other people involved in crisis response to make well-informed and targeted decisions about from which geographical locations and time periods more genetic samples may be required to fully understand the outbreak. Our approach relies on the application of Transcendental Information Cascades to a set of temporally ordered nucleotide sequences and we apply it to real-world data that was collected during the currently ongoing outbreak of the novel 2019-nCoV coronavirus. We assess information-theoretic and network-theoretic measures that characterise the resulting complex network and suggest touching points and temporal pathways that are of interest for deeper investigation by geneticists and epidemiologists.</jats:p>",2020-02-11,['Markus Luczak-Roesch'],,,,True
36a5f6d55d7c5f67d4344e36da0a72856ad3dda0,medrxiv,"The Novel Coronavirus, 2019-nCoV, is Highly Contagious and More Infectious Than Initially Estimated",doi.org/10.1101/2020.02.07.20021154,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The novel coronavirus (2019-nCoV) is a recently emerged human pathogen that has spread widely since January 2020. Initially, the basic reproductive number, R0, was estimated to be 2.2 to 2.7. Here we provide a new estimate of this quantity. We collected extensive individual case reports and estimated key epidemiology parameters, including the incubation period. Integrating these estimates and high-resolution real-time human travel and infection data with mathematical models, we estimated that the number of infected individuals during early epidemic double every 2.4 days, and the R0 value is likely to be between 4.7 and 6.6. We further show that quarantine and contact tracing of symptomatic individuals alone may not be effective and early, strong control measures are needed to stop transmission of the virus.</jats:p>",2020-02-11,"['Steven Sanche', 'Yen Ting Lin', 'Chonggang Xu', 'Ethan Romero-Severson', 'Nick Hengartner', 'Ruian Ke']",,,,True
ba92c589f077b55e9cd13264d619c2ffe9d3ce7a,medrxiv,Transmission Dynamics of 2019-nCoV in Malaysia,doi.org/10.1101/2020.02.07.20021188,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>This paper focuses on the formulation of a deterministic 2019-nCov transmission model by considering the exposed and recovered populations with immunity. The scenario of the simulation is depicted based on the patient zero in Malaysia. The transmission model is found to be able to predict the next confirmed case given a single case introduced in a fully susceptible population. The mathematical model is developed based on the SEIR model which has susceptible, exposed, infectious and recovered populations. The system of equations which were obtained were solved numerically and the simulation results were analyzed. The analysis includes the impact of the disease if no control is taken.</jats:p>",2020-02-11,"['Jane Labadin', 'Boon Hao Hong']",,,,True
483195e49d2b961610a8ef31b93219089dd7b4e5,medrxiv,Tracking the spread of novel coronavirus (2019-nCoV) based on big data,doi.org/10.1101/2020.02.07.20021196,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The novel coronavirus (2019-nCoV) appeared in Wuhan in late 2019 have infected 34,598 people, and killed 723 among them until 8th February 2020. The new virus has spread to at least 316 cities (until 1st February 2020) in China. We used the traffic flow data from Baidu Map, and number of air passengers who left Wuhan from 1st January to 26th January, to quantify the potential infectious people. We developed multiple linear models with local population and air passengers as predicted variables to explain the variance of confirmed cases in every city across China. We found the contribution of air passengers from Wuhan was decreasing gradually, but the effect of local population was increasing, indicating the trend of local transmission. However, the increase of local transmission is slow during the early stage of novel coronavirus, due to the super strict control measures carried out by government agents and communities.</jats:p>",2020-02-11,"['Xumao Zhao', 'Xiang Liu', 'Xinhai Li']",,,,False
2cc809ed4d5c3640ee2351fdb1876e8ff6c01b51,medrxiv,Feasibility of controlling 2019-nCoV outbreaks by isolation of cases and contacts,doi.org/10.1101/2020.02.08.20021162,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: To assess the viability of isolation and contact tracing to control onwards transmission from imported cases of 2019-nCoV.  Methods: We developed a stochastic transmission model, parameterised to the 2019-nCoV outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a 2019 nCoV-like pathogen. We considered scenarios that varied in: the number of initial cases; the basic reproduction number R0; the delay from symptom onset to isolation; the probability contacts were traced; the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort.   Findings: While simulated outbreaks starting with only 5 initial cases, R0 of 1.5 and little transmission before symptom onset could be controlled even with low contact tracing probability, the prospects of controlling an outbreak dramatically dropped with the number of initial cases, with higher R0, and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R0 of 1.5 were controllable with under 50% of contacts successfully traced. For R0 of 2.5 and 3.5, more than 70% and 90% of contacts respectively had to be traced to control the majority of outbreaks. The delay between symptom onset and isolation played the largest role in determining whether an outbreak was controllable for lower values of R0. For higher values of R0 and a large initial number of cases, contact tracing and isolation was only potentially feasible when less than 1% of transmission occurred before symptom onset.  Interpretation: We found that in most scenarios contact tracing and case isolation alone is unlikely to control a new outbreak of 2019-nCov within three months. The probability of control decreases with longer delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts.</jats:p>",2020-02-11,"['Joel Hellewell', 'Sam Abbott', 'Amy Gimma', 'Nikos I Bosse', 'Christopher I Jarvis', 'Timothy W Russell', 'James D Munday', 'Adam J Kucharski', 'W John Edmunds', 'CMMID nCoV working group', 'Sebastian Funk', 'Rosalind M Eggo']",,,,True
385fac6bd63f6cab6f14872bdd6542bb7391bc62,medrxiv,Caution on Kidney Dysfunctions of 2019-nCoV Patients,doi.org/10.1101/2020.02.08.20021212,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Until 24:00 of February 7th 2020, 31774 laboratory-confirmed cases of novel coronavirus (2019-nCoV) infection have been reported, including 6101 severe cases in critical conditions and 722 deaths. The critical and urgent need at this moment is to find an effective treatment strategy with available means to prevent these thousands of severe inpatients from worsening and dying. It has been recently known that the 2019-nCoV shares a common cellular mechanism with the severe acute respiratory syndrome-associated coronavirus (SARS-CoV). Thus, we surveyed a previous retrospective case study on SARS which showed that acute renal impairment was uncommon in SARS but carried a formidably high mortality (91.7%, 33 of 36 cases). Here we report an ongoing case study on kidney functions in 59 patients infected by 2019-nCoV (including 28 diagnosed as severe cases and 3 deaths). 63% (32/51) of the patients exhibited proteinuria, indicative of renal impairment. 19% (11/59) and 27% (16/59) of the patients had an elevated level of plasma creatinine and urea nitrogen respectively. The computerized tomography (CT) scan showed radiographic abnormalities of the kidneys in 100% (27/27) of the patients. Together, these multiple lines of evidence point to the idea that renal impairment is common in 2019-nCov patients, which may be one of the major causes of the illness by the virus infection and also may contribute to multi-organ failure and death eventually. Therefore, we strongly suggest exercising a high degree of caution in monitoring the kidney functions of 2019-nCoV patients and, very importantly, that applying potential interventions including continuous renal replacement therapies (CRRT) for protecting kidney functions as early as possible, particular for those with plasma creatinine rising, is key to preventing fatality.</jats:p>",2020-02-12,,,,,False
5bbc428de7fc2f10c24d8439edda26d84b319687,medrxiv,Estimation of the Time-Varying Reproduction Number of COVID-19 Outbreak in China,doi.org/10.1101/2020.02.08.20021253,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: The 2019-nCoV outbreak in Wuhan, China has attracted world-wide attention. As of February 11, 2020, a total of 44730 cases of novel coronavirus-infected pneumonia associated with COVID-19 were confirmed by the National Health Commission of China. Methods: Three approaches, namely Poisson likelihood-based method (ML), exponential growth rate-based method (EGR) and stochastic Susceptible-Infected-Removed dynamic model-based method (SIR), were implemented to estimate the basic and controlled reproduction numbers. Results: A total of 71 chains of transmission together with dates of symptoms onset and 67 dates of infections were identified among 5405 confirmed cases outside Hubei as reported by February 2, 2020. Based on this information, we find the serial interval having an average of 4.41 days with a standard deviation of 3.17 days and the infectious period having an average of 10.91 days with a standard deviation of 3.95 days. Conclusions: The controlled reproduction number is declining. It is lower than one in most regions of China, but is still larger than one in Hubei Province. Sustained efforts are needed to further reduce the Rc to below one in order to end the current epidemic.</jats:p>",2020-02-11,"['Chong You', 'Yuhao Deng', 'Wenjie Hu', 'Jiarui Sun', 'Qiushi Lin', 'Feng Zhou', 'Cheng Heng Pang', 'Yuan Zhang', 'Zhengchao Chen', 'Xiao-Hua Zhou']",,,,True
5cfb44ecdfb61b2898b6cf7315b1e810874a9560,medrxiv,Assessing the plausibility of subcritical transmission of 2019-nCoV in the United States,doi.org/10.1101/2020.02.08.20021311,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Abstract: The 2019-nCoV outbreak has raised concern of global spread.  While person-to-person transmission within the Wuhan district has led to a large outbreak, the transmission potential outside of the region remains unclear.  Here we present a simple approach for determining whether the upper limit of the confidence interval for the reproduction number exceeds one for transmission in the United States, which would allow endemic transmission.  As of February 7, 2020, the number of cases in the United states support subcritical transmission, rather than ongoing transmission.  However, this conclusion can change if pre-symptomatic cases resulting from human-to-human transmission have not yet been identified.</jats:p>",2020-02-11,"['Seth Blumberg', 'Thomas M Lietman', 'Travis C Porco']",,,,True
5c31897d01f3edc7f58a0f03fceec2373fcfdc3d,medrxiv,The effect of travel restrictions on the spread of the 2019 novel coronavirus (2019-nCoV) outbreak,doi.org/10.1101/2020.02.09.20021261,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Motivated by the rapid spread of a novel coronavirus (2019-nCoV) in Mainland China, we use a global metapopulation disease transmission model to project the impact of both domestic and international travel limitations on the national and international spread of the epidemic. The model is calibrated on the evidence of internationally imported cases before the implementation of the travel quarantine of Wuhan. By assuming a generation time of 7.5 days, the reproduction number is estimated to be 2.4 [90% CI 2.2-2.6]. The median estimate for number of cases before the travel ban implementation on January 23, 2020 is 58,956 [90% CI 40,759 - 87,471] in Wuhan and 3,491 [90% CI 1,924 - 7,360] in other locations in Mainland China.  The model shows that as of January 23, most Chinese cities had already received a considerable number of infected cases, and the travel quarantine delays the overall epidemic progression by only 3 to 5 days. The travel quarantine has a more marked effect at the international scale, where we estimate the number of case importations to be reduced by 80% until the end of February. Modeling results also indicate that sustained 90% travel restrictions to and from Mainland China only modestly affect the epidemic trajectory unless combined with a 50% or higher reduction of transmission in the community.</jats:p>",2020-02-11,"['Matteo Chinazzi', 'Jessica T. Davis', 'Marco Ajelli', 'Corrado Gioannini', 'Maria Litvinova', 'Stefano Merler', 'Ana Pastore y Piontti', 'Luca Rossi', 'Kaiyuan Sun', 'Cécile Viboud', 'Xinyue Xiong', 'Hongjie Yu', 'M. Elizabeth Halloran', 'Ira M. Longini', 'Alessandro Vespignani']",,,,True
2913d91f13fd59c698f68ba63008d8e0550c0607,medrxiv,Spatially Explicit Modeling of 2019-nCoV Epidemic Trend based on Mobile Phone Data in Mainland China,doi.org/10.1101/2020.02.09.20021360,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>IAs of February 11, 2020, all prefecture-level cities in mainland China have reported confirmed cases of 2019 novel coronavirus (2019-nCoV), but the city-level epidemical dynamics is unknown. The aim of this study is to model the current dynamics of 2019-nCoV at city level and predict the trend in the next 30 days under three possible scenarios in mainland China. We developed a spatially explicit epidemic model to consider the unique characteristics of the virus transmission in individual cities. Our model considered that the rate of virus transmission among local residents is different from those with Wuhan travel history due to the self-isolation policy. We introduced a decay rate to quantify the effort of each city to gradually control the disease spreading. We used mobile phone data to obtain the number of individuals in each city who have travel history to Wuhan. This city-level model was trained using confirmed cases up to February 10, 2020 and validated by new confirmed cases on February 11, 2020. We used the trained model to predict the future dynamics up to March 12, 2020 under different scenarios: the current trend maintained, control efforts expanded, and person-to-person contact increased due to work resuming.  We estimated that the total infections in mainland China would be 72172, 54348, and 149774 by March 12, 2020 under each scenario respectively. Under the current trend, all cities will show the peak point of daily new infections by February 21. This date can be advanced to February 14 with control efforts expanded or postponed to February 26 under pressure of work resuming. Except Wuhan that cannot eliminate the disease by March 12, our model predicts that 95.4%, 100%, and 75.7% cities will have no new infections by the end of February under three scenarios.  The spatial pattern of our prediction could help the government allocate resources to cities that have a more serious epidemic in the next 30 days.</jats:p>",2020-02-11,"['Xiaolin Zhu', 'Aiyin Zhang', 'Shuai Xu', 'Pengfei Jia', 'Xiaoyue Tan', 'Jiaqi Tian', 'Tao Wei', 'Zhenxian Quan', 'Jiali Yu']",,,,True
d2609c4d8837558f4b8f32170422ce1cd12425a6,medrxiv,Assessing the Tendency of 2019-nCoV (COVID-19) Outbreak in China,doi.org/10.1101/2020.02.09.20021444,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Since December 8, 2019, the spread of COVID-19 is increasing every day. It is particularly important to predict the trend of the epidemic for the timely adjustment of the economy and industries. We proposed a Flow-SEHIR model in this paper, based on which we further analyzed the trends of 2019-nCoV (COVID-19) in China.    The results show that the basic reproductive numbers R0 of COVID-19 is 3.56 (95% CI: 2.31-4.81). The number of daily confirmed new cases reaches the inflection point on Feb. 6-10 outside Hubei. For the maximum of infected cases number, the predicted peak value in China except Hubei was estimated to be 13806 (95% CI: 11926-15845). The peak arrival time is on March 3-9. The temporal number of patients in most areas of China outside Hubei will peak from March 12 to March 15. The peak values of more than 73.5% provinces or regions in China will be controlled within 1000. According to Flow-SEHIR model and estimations from the data of evacuation of nationals from Wuhan, the peak cumulative number of patients in Hubei was estimated to be 403481 (95% CI: 143284-1166936).</jats:p>",2020-02-11,"['Qinghe Liu', 'Zhicheng Liu', 'Deqiang Li', 'Zefei Gao', 'Junkai Zhu', 'Junyan Yang', 'Qiao Wang']",,,,True
dcd7a1235ea74e3ef71d051103bf8a64c3c8f457,medrxiv,The lockdown of Hubei Province causing different transmission dynamics of the novel coronavirus (2019-nCoV) in Wuhan and Beijing,doi.org/10.1101/2020.02.09.20021477,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: After the outbreak of novel coronavirus (2019-nCoV) starting in late 2019, a number of researchers have reported the predicted the virus transmission dynamics. However, under the strict control policy the novel coronavirus does not spread naturally outside Hubei Province, and none of the prediction closes to the real situation.  Methods and findings: We used the traditional SEIR model, fully estimated the effect of control measures, to predict the virus transmission in Wuhan, the capital city of Hubei Province, and Beijing. We forecast that the outbreak of 2019-nCoV would reach its peak around March 6±10 in Wuhan and March 20±16 in Beijing, respectively. The infectious population in Beijing would be much less (only 0.3%) than those in Wuhan at the peak of this transmission wave. The number of confirmed cases in cities inside Hubei Province grow exponentially, whereas those in cities outside the province increase linearly. Conclusions: The unprecedented province lockdown substantially suspends the national and global outbreak of 2019-nCoV.</jats:p>",2020-02-11,"['Xinhai Li', 'Xumao Zhao', 'Yuehua Sun']",,,,True
815745bf1b522d33fd7371cc9a6561a2a93ef87e,medrxiv,Simulating the infected population and spread trend of 2019-nCov under different policy by EIR model,doi.org/10.1101/2020.02.10.20021519,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Chinese government has taken strong measures in response to the epidemic of new coronavirus (2019-nCoV) from Jan.23, 2020. The number of confirmed infected individuals are still increasing rapidly. Estimating the accurate infected population and the future trend of epidemic spreading under control measures is significant and urgent. There have been reports external icon of spread from an infected patient with no symptoms to a close contact, which means the incubation individuals may has the possibility of infectiousness. However, the traditional transmission model, Susceptible-Exposed-Infectious-Recovered (SEIR) model, assumes that the exposed individual is being infected but without infectiousness. Thus, the estimating infected populations based on SEIR model from the existing literatures seems too far more than the official reported data. Here, we inferred that the epidemic could be spread by exposed (incubation) individuals. Then, we provide a new Exposed-identified-Recovered (EIR) model, and simulated the epidemic spreading processes from free propagation phase to extremely control phase. Then, we estimate of the size of the epidemic and forecast the future development of the epidemics under strong prevention interventions. According to the spread characters of 2019-nCov, we construct a novel EIR compartment system dynamics model. This model integrates two phases of the epidemic spreading: before intervention and after intervention. We assume that 2019-nCov is firstly spread without intervention then the government started to take strong quarantine measures. Use the latest reported official data, we estimate the basic parameters of the model and the basic reproduction number of 2019-nCov. Then, based on this model, we simulate the future spread of the epidemics. Both the infected population and the spreading trend of 2019-nCov under different prevention policy scenarios are estimated. The epidemic spreading trends under different quarantine rate and action starting date of prevention policy are simulated and compared.</jats:p>",2020-02-12,"['Hao Xiong', 'Huili Yan']",,,,True
48656efc59191537073975938f25f201524971af,medrxiv,Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage,doi.org/10.1101/2020.02.10.20021584,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Severe ill patients with 2019 novel coronavirus (2019-nCoV) infection progressed rapidly to acute respiratory failure. We aimed to select the most useful prognostic factor for severe illness incidence. Methods: The study prospectively included 61 patients with 2019-nCoV infection treated at Beijing Ditan Hospital from January 13, 2020 to January 31, 2020. Prognostic factor of severe illness was selected by the LASSO COX regression analyses, to predict the severe illness probability of 2019-CoV pneumonia. The predictive accuracy was evaluated by concordance index, calibration curve, decision curve and clinical impact curve. Results: The neutrophil-to-lymphocyte ratio (NLR) was identified as the independent risk factor for severe illness in patients with 2019-nCoV infection. The NLR had a c-index of 0.807 (95% confidence interval, 0.676-0.38), the calibration curves fitted well, and the decision curve and clinical impact curve showed that the NLR had superior standardized net benefit. In addition, the incidence of severe illness was 9.1% in age ≥ 50 and NLR &lt; 3.13 patients, and half of patients with age ≥ 50 and NLR ≥ 3.13 would develop severe illness. Based on the risk stratification of NLR with age, the study developed a 2019-nCoV pneumonia management process. Conclusions: The NLR was the early identification of risk factors for 2019-nCoV severe illness. Patients with age ≥ 50 and NLR ≥ 3.13 facilitated severe illness, and they should rapidly access to intensive care unit if necessary.</jats:p>",2020-02-12,"['Jingyuan Liu', 'Yao Liu', 'Pan Xiang', 'Lin Pu', 'Haofeng Xiong', 'Chuansheng Li', 'Ming Zhang', 'Jianbo Tan', 'Yanli Xu', 'Rui Song', 'Meihua Song', 'Lin Wang', 'Wei Zhang', 'Bing Han', 'Li Yang', 'Xiaojing Wang', 'Guiqin Zhou', 'Ting Zhang', 'Ben Li', 'Yanbin Wang', 'Zhihai Chen', 'Xianbo Wang']",,,,True
f53ca84858915f9a8068816ac7416f1222089d55,medrxiv,Epidemiological and clinical features of the 2019 novel coronavirus outbreak in China,doi.org/10.1101/2020.02.10.20021675,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Our manuscript was based on surveillance cases of COVID-19 identified before January 26, 2020. As of February 20, 2020, the total number of confirmed cases in mainland China has reached 18 times of the number in our manuscript. While the methods and the main conclusions in our original analyses remain solid, we decided to withdraw this preprint for the time being, and will replace it with a more up-to-date version shortly. Should you have any comments or suggestions, please feel free to contact the corresponding author.</jats:p>",2020-02-11,"['Yang Yang', 'Qingbin Lu', 'Mingjin Liu', 'Yixing Wang', 'Anran Zhang', 'Neda Jalali', 'Natalie Dean', 'Ira Longini', 'M. Elizabeth Halloran', 'Bo Xu', 'Xiaoai Zhang', 'Liping Wang', 'Wei Liu', 'Liqun Fang']",,,,False
06c1b3535b83251cf92c01258b5048beeab7a460,medrxiv,Beyond R0: the importance of contact tracing when predicting epidemics,doi.org/10.1101/2020.02.10.20021725,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The basic reproductive number --- R<jats:sub>0</jats:sub> --- is one of the most common and most commonly misapplied numbers in public health.  Nevertheless, estimating R<jats:sub>0</jats:sub> for every transmissible pathogen, emerging or endemic, remains a priority for epidemiologists the world over.  Although often used to compare outbreaks and forecast pandemic risk, this single number belies the complexity that two different pathogens can exhibit, even when they have the same R<jats:sub>0</jats:sub>. Here, we show how predicting outbreak size requires both an estimate of R<jats:sub>0</jats:sub> and an estimate of the heterogeneity in the number of secondary infections.  To facilitate rapid determination of outbreak risk, we propose a reformulation of a classic result from random network theory that relies on contact tracing data to simultaneously determine the first moment (R<jats:sub>0</jats:sub>) and the higher moments (representing the heterogeneity) in the distribution of secondary infections.  Further, we show how this framework is robust in the face of the typically limited amount of data for emerging pathogens. Lastly, we demonstrate that without data on the heterogeneity in secondary infections for emerging pathogens like 2019-nCoV, the uncertainty in outbreak size ranges dramatically, in the case of 2019-nCoV from 5-40% of susceptible individuals. Taken together, our work highlights the critical need for contact tracing during emerging infectious disease outbreaks and the need to look beyond R<jats:sub>0</jats:sub> when predicting epidemic size.</jats:p>",2020-02-12,"['Laurent Hébert-Dufresne', 'Benjamin M. Althouse', 'Samuel V. Scarpino', 'Antoine Allard']",,,,True
3687fe96c5a48eca349ea4bacf8bb1e1a1e54bfe,medrxiv,Statistical Inference for Coronavirus Infected Patients in Wuhan,doi.org/10.1101/2020.02.10.20021774,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Importance: The new coronavirus outbreak has seriously affected the quality of life in China. Wuhan is the disaster area, where the number of cases has increased rapidly. However, the current measures of infected patients in Wuhan are still underestimated. Objective: To estimate the overall infected patients in Wuhan from several sampled data. The correct estimated infected patients can be helpful for the government to arrange the needed beds in hospital wards to meet the actual needs. Design: We proposed to use the sampling survey to estimate the overall infected patients in Wuhan. The sampling survey is a kind of non-comprehensive survey. It selected some units from all the survey objects to carry out the survey and made the estimation and inference to all the survey objects. Sampling surveys can obtain information that reflects the overall situation, although it is not a comprehensive survey.   Setting: We estimated the overall infection rate in Wenzhou city, which has a better data collection system. Simultaneously, another different samples of Wuhan tourists to Singapore will be used to validate the infection rate in Wenzhou city. Combined these two samples, we give the estimation of the number of infected patients in Wuhan and other prefecture-level cities in Hubei Province.  Participants: The number of people who returned from Wuhan to Wenzhou was selected from the daily notification of the pneumonia epidemic caused by a new coronavirus infection in the city.   Exposures for observational studies: The daily rate of the pneumonia epidemic caused by the new coronavirus infection in Wenzhou City. The numerator is the number of people diagnosed and whether each person diagnosed had a history of living in Wuhan. The denominator is the total number of people returning to Wenzhou from Wuhan. Based on this rate, it is reasonable to predict the number of the infected patients.</jats:p>",2020-02-12,"['Yongdao Zhou', 'Jianghu Dong']",,,,False
eec5b4ce2de8d9d00be664e6af79cac476991bbf,medrxiv,"Distribution of the 2019-nCoV Epidemic and Correlation with Population Emigration from Wuhan, China",doi.org/10.1101/2020.02.10.20021824,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>BACKGROUNDS: The ongoing new coronavirus (2019-nCoV) pneumonia outbreak is spreading in China and has not reached its peak. Five millions of people had emigrated from Wuhan before the city lockdown, which potentially represent a source of virus spreaders. Case distribution and its correlation with population emigration from Wuhan in early epidemic are of great importance for early warning and prevention of future outbreak.  METHODS: The officially reported cases of 2019-nCoV pneumonia were collected as of January 30, 2020. Time and location information of these cases were extracted analyzed with ArcGIS and WinBUGS. Population migration data of Wuhan City and Hubei province were extracted from Baidu Qianxi and analyzed for their correlation with case number. FINDINGS: The 2019-nCoV pneumonia cases were predominantly distributed in Hubei and other provinces of South China. Hot spot provinces included Sichuan and Yunnan provinces that are adjacent to Hubei. While Wuhan city has the highest number of cases, the time risk is relatively stable. Numbers of cases in some cities are relatively low, but the time risks are continuously rising. The case numbers of different provinces and cities of Hubei province were highly correlated with the emigrated populations from Wuhan. Lockdown of 19 cities of Hubei province, and implementation of nationwide control measures efficiently prevented the exponential growth of case number. INTERPRETATION: Population emigrated from Wuhan was the main infection source for other cities and provinces. Some cities with low case number but were in rapid increase. Due to the upcoming Spring Festival return transport wave, understanding of the trends of risks in different regions is of great significance for preparedness for both individuals and institutions.</jats:p>",2020-02-12,"['Zeliang Chen', 'Qi Zhang', 'Yi Lu', 'Xi Zhang', 'Wenjun Zhang', 'Cheng Guo', 'Conghui Liao', 'Qianlin Li', 'Xiaohu Han', 'Jiahai Lu']",,,,True
15ad534bb2ec7bc4b0ee83ddac11a1b837d743c6,medrxiv,Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP),doi.org/10.1101/2020.02.10.20021832,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: To explore the cellular immunity and cytokines status of NCP patients and to predict the correlation between the cellular immunity levels, cytokines and the severity of patients. Methods: 123 NCP patients were divided into mild and severe groups. Peripheral blood was collected, lymphocyte subsets and cytokines were detected. Correlation analysis was performed on the lymphocyte subsets and cytokines, and the differences between the indexes of the two groups were analyzed. Results: 102 mild and 21 severe patients were included. Lymphocyte subsets were reduced in two groups. The proportion of CD8 + T reduction in the mild and severe group was 28.43% and 61.9%, respectively; The proportion of B cell reduction was 25.49% and 28.57%; The proportion of NK cell reduction was 34.31% and 47.62%; The detection value of IL-6 was 0 in 55.88% of the mild group, mild group has a significantly lower proportion of patients with IL-6 higher than normal than severe group; There was no significant linear correlation between the lymphocyte subsets and cytokines, while significant differences were noticed between the two groups in CD4 + T, CD8 + T, IL-6 and IL-10. Conclusions: Low levels of CD4+T and CD8+T are common in severe NCP. IL-6 and IL-10 levels were higher in severe patients. T cell subsets and cytokines can be used as one of the basis for predicting the transition from mild to severe. Large number of samples are still needed to confirm the ""warning value"" of CD4 + T, CD8 + T IL-6 and IL-10.</jats:p>",2020-02-12,"['Suxin Wan', 'Qingjie Yi', 'Shibing Fan', 'Jinglong Lv', 'Xianxiang Zhang', 'Lian Guo', 'Chunhui Lang', 'Qing Xiao', 'Kaihu Xiao', 'Zhengjun Yi', 'Mao Qiang', 'Jianglin Xiang', 'Bangshuo Zhang', 'Yongping Chen']",,,,True
2cfe7a4cc1fceed0ad7ffbd6244a61e0b2c3ac8b,medrxiv,Facemask shortage and the coronavirus disease (COVID-19) outbreak: Reflection on public health measures,doi.org/10.1101/2020.02.11.20020735,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>To the best of our knowledge, this is the first study to investigate the facemask shortage during the novel coronavirus pneumonia (COVID-19) outbreak in China. We have summarized in detail the management strategies implemented by the Chinese governments during the outbreaks. By considering three scenarios for the outbreak development, we simulated the facemasks availability from late-December 2019 to late-April 2020 and estimated the duration of sufficient facemask supplies. Our findings showed that if the COVID-19 outbreak occurred only in Wuhan city or Hubei province, facemask shortage would not appear with the existing public health measures. However, if the outbreak occurred in the whole of China, a shortage of facemask could be substantial assuming no alternative public health measures. Supplies of facemasks in the whole of China would have been sufficient for both healthcare workers and the general population if the COVID-19 outbreak only occurred in Wuhan city or Hubei province. However, if the outbreak occurred in the whole of China, facemask supplies in China could last for 5 days if under the existing public health measures and a shortage of 853 million facemasks is expected by 30 Apr 2020. Assuming a gradually decreased import volume, we estimated that dramatic increase in productivity (42.7 times of the usual level) is needed to mitigate the facemask crisis by the end of April. In light of the COVID-19 outbreak in China, a shortage of facemasks and other medical resources can considerably compromise the efficacy of public health measures. Effective public health measures should also consider the adequacy and affordability of medical resources. Global collaboration should be strengthened to prevent the development of a global pandemic from a regional epidemic via easing the medical resources crisis in the affected countries.</jats:p>",2020-02-12,"['Huailiang Wu', 'Jian Huang', 'Casper JP Zhang', 'Zonglin He', 'Wai-kit Ming']",,,,True
8b88901d0bb033af3a18ebcdf7f2aa7110b21504,medrxiv,Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections,doi.org/10.1101/2020.02.11.20021493,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background:  The outbreak of novel coronavirus pneumonia (NCP) caused by 2019-nCoV spread rapidly, and elucidation the diagnostic accuracy of different respiratory specimens is crucial for the control and treatment of this diseases.   Methods:  Respiratory samples including nasal swabs, throat swabs, sputum and bronchoalveolar lavage fluid (BALF) were collected from Guangdong CDC confirmed NCP patients, and viral RNAs were detected using a CFDA approved detection kit. Results were analyzed in combination with sample collection date and clinical information.  Finding:  Except for BALF, the sputum possessed the highest positive rate (74.4%~88.9%), followed by nasal swabs (53.6%~73.3%) for both severe and mild cases during the first 14 days after illness onset (d.a.o). For samples collected ≥ 15 d.a.o, sputum and nasal swabs still possessed a high positive rate ranging from 42.9%~61.1%. The positive rate of throat swabs collected ≥ 8 d.a.o was low, especially in samples from mild cases. Viral RNAs could be detected in all the lower respiratory tract of severe cases, but not the mild cases. CT scan of cases 02, 07 and 13 showed typical viral pneumonia with ground glass opacity, while no viral RNAs were detected in first three or all the upper respiratory samples.     Interpretation:  Sputum is most accurate for laboratory diagnosis of NCP, followed by nasal swabs. Detection of viral RNAs in BLAF is necessary for diagnosis and monitoring of viruses in severe cases. CT scan could serve as an important make up for the diagnosis of NCP.  Funding  National Science and Technology Major Project, Sanming Project of Medicine and China Postdoctoral Science Foundation.</jats:p>",2020-02-12,"['Yang Yang', 'Minghui Yang', 'Chenguang Shen', 'Fuxiang Wang', 'Jing Yuan', 'Jinxiu Li', 'Mingxia Zhang', 'Zhaoqin Wang', 'Li Xing', 'Jinli Wei', 'Ling Peng', 'Gary Wong', 'Haixia Zheng', 'Mingfeng Liao', 'Kai Feng', 'Jianming Li', 'Qianting Yang', 'Juanjuan Zhao', 'Zheng Zhang', 'Lei Liu', 'Yingxia Liu']",,,,True
88f3731c0dc1aa1a13879ce3ebdbf69767e5c9f5,medrxiv,Ophthalmologic evidence against the interpersonal transmission of 2019 novel coronavirus through conjunctiva,doi.org/10.1101/2020.02.11.20021956,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: The emerging 2019 novel coronavirus (2019−nCoV) has pushed several countries into state of emergency all over the world. The possible transmission of 2019−nCoV by conjunctiva is controversial and has substantial public health implications. Methods: A retrospective cohort study was initiated to investigate the possible transmission of 2019−nCoV through aerosol contact with conjunctiva. We enrolled 67 cases of confirmed or suspected cases of novel coronavirus pneumonia (NCP) during 17−28 Jan 2020. Nasopharyngeal and conjunctival swabs were collected for real time RT-PCR analysis to detect 2019−nCoV. Results: 63 patients were identified as laboratory−confirmed NCP and the remaining four were suspected NCP. Conjunctival swab samples from one NCP patient yielded positive PCR results and two NCP patients yielded probable positive PCR results. None of the three patients had ocular symptoms. The only one NCP patient with conjunctivitis as the first symptom had negative conjunctival sac 2019−nCoV test. Conjunctival swab samples from the four suspected cases of NCIP were negative. Conclusion: 2019−nCoV can be detected in the conjunctival sac of patients with NCP. Through clinical analysis, viral transmission via the conjunctival route was not supported by the data. Good clinical protection can effectively cut off the transmission path.</jats:p>",2020-02-12,"['Yunyun Zhou', 'Yuyang Zeng', 'Yongqing Tong', 'ChangZheng Chen']",,,,False
4bd6feacc454c6a777073bbc4b71d895d0b268e6,medrxiv,"Epidemiological and Clinical Characteristics of 17 Hospitalized Patients with 2019 Novel Coronavirus Infections Outside Wuhan, China",doi.org/10.1101/2020.02.11.20022053,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>An increasing number of cases of novel coronavirus pneumonia (NCP) infected with 2019-nCoV have been identified in Wuhan and other cities in China, since December 2019. We analyzed data on the 17 confirmed cases in Dazhou to provide the epidemiologic characteristics of NCP outside Wuhan. Among them, 12 patients were still quarantined in the hospital, 5 patients were discharged NCP patients according to the national standards. Compared with non-discharged NCP patients, the discharged NCP patients had younger ages. Moreover, discharged NCP patients had higher heart rate, lymphocytes levels and monocytes levels than non-discharged NCP patients on admission to the hospital. Notably, all of 17 patients had abnormal increased C-reactive protein levels, and 16 patients had abnormal computed tomography images. This study provided some information that younger age, higher lymphocytes levels and monocytes levels at the diagnoses of 2019-nCoV may contributed to faster recovery and better therapeutic outcome.</jats:p>",2020-02-12,"['Jie Li', 'Shilin Li', 'Yurui Cai', 'Qin Liu', 'Xue Li', 'Zhaoping Zeng', 'Yanpeng Chu', 'Fangcheng Zhu', 'Fanxin Zeng']",,,,False
f32224faabfe662f11673a7e218af2cb37b4ef5f,medrxiv,Primary Care Practitioners' Response to 2019 Novel Coronavirus Outbreak in China,doi.org/10.1101/2020.02.11.20022095,,,See https://www.medrxiv.org/submit-a-manuscript,<jats:p>None</jats:p>,2020-02-12,"['Zhijie Xu', 'Yi Qian', 'Lizheng Fang', 'Mi Yao']",,,,False
004f0f8bb66cf446678dc13cf2701feec4f36d76,medrxiv,Healthcare-resource-adjusted vulnerabilities towards the 2019-nCoV epidemic across China,doi.org/10.1101/2020.02.11.20022111,,,See https://www.medrxiv.org/submit-a-manuscript,<jats:p>We integrate the human movement and healthcare resource data to identify cities with high vulnerability towards the 2019-nCoV epidemic with respect to available health resources. The results inform public health responses in multiple ways.</jats:p>,2020-02-12,"['Hanchu Zhou', 'Jianan Yang', 'Kaichen Tang', 'Qingpeng Zhang', 'zhidong cao', 'Dirk Pfeiffer', 'Daniel Dajun Zeng']",,,,True
2858f25f5364b0ef37ceeaa370471ee6b3fac29d,medrxiv,"Data-Based Analysis, Modelling and Forecasting of the COVID-19 outbreak",doi.org/10.1101/2020.02.11.20022186,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Since the first suspected case of coronavirus disease-2019 (COVID-19) on December 1st, 2019, in Wuhan, Hubei Province, China, a total of 40,235 confirmed cases and 909 deaths have been reported in China up to February 10, 2020, evoking fear locally and internationally.  Here, based on the publicly available epidemiological data for Hubei, China from January 11 to February 10, 2020, we provide estimates of the main epidemiological parameters. In particular, we provide an estimation of the case fatality and case recovery ratios, along with their 90% confidence intervals as the outbreak evolves. On the basis of a Susceptible-Infected-Recovered-Dead (SIDR) model, we provide estimations of the basic reproduction number (R0), and the per day infection mortality and recovery rates. By calibrating the parameters of the SIRD model to the reported data, we also attempt to forecast the evolution of the of the outbreak at the epicenter three weeks ahead, i.e. until February 29. As the number of infected individuals, especially of those with asymptomatic or mild courses, is suspected to be much higher than the official numbers, which can be considered only as a subset of the actual numbers of infected and recovered cases in the total population, we have repeated the calculations under a second scenario that considers twenty times the number of confirmed infected cases and forty times the number of recovered, leaving the number of deaths unchanged. Based on the reported data, the expected value of R0 as computed considering the period from the 11th of January until the 18th of January, using the official counts of confirmed cases was found to be ~4.6, while the one computed under the second scenario was found to be ~3.2. Thus, based on the SIRD simulations, the estimated average value of R0 was found to be ~2.6 based on confirmed cases and ~2 based on the second scenario. Our forecasting flashes a note of caution for the presently unfolding outbreak in China. Based on the official counts for confirmed cases, the simulations suggest that the cumulative number of infected could reach 180,000 (with lower bound of 45,000) by February 29. Regarding the number of deaths, simulations forecast that on the basis of the up to the 10th of February reported data, the death toll might exceed 2,700 (as a lower bound) by February 29. Our analysis further reveals a significant decline of the case fatality ratio from January 26 to which various factors may have contributed, such as the severe control measures taken in Hubei, China (e.g. quarantine and hospitalization of infected individuals), but mainly because of the fact that the actual cumulative numbers of infected and recovered cases in the population most likely are much higher than the reported ones. Thus, in a scenario where we have taken twenty times the confirmed number of infected and forty times the confirmed number of recovered cases, the case fatality ratio is around 0.15% in the total population. Importantly, based on this scenario, simulations suggest a slow down of the outbreak in Hubei at the end of February.</jats:p>",2020-02-13,"['Cleo Anastassopoulou', 'Lucia Russo', 'Athanasios Tsakris', 'Constantinos Siettos']",,,,True
fbc41a8e025cd6eb2d7c156aad3b6923af2349c4,medrxiv,"Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCoV, in the nasal tissue",doi.org/10.1101/2020.02.11.20022228,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>A novel coronavirus (2019-nCoV) was first identified in Wuhan, Hubei Province, and then spreads to the other Provinces of China. WHO decides to determine a Public Health Emergency of International Concern (PHEIC) of 2019-nCoV. 2019-nCov was reported to share the same receptor, Angiotensin-converting enzyme 2 (ACE2), with SARS-Cov. Here based on the public single-cell RNA-Seq datasets, we analyzed the ACE2 RNA expression profile in the tissues at different locations of the respiratory tract. The result indicates that the ACE2 expression appears in nasal epithelial cells. We found that the size of this population of ACE2-expressing nasal epithelial cells is comparable with the size of the population of ACE2-expression type II alveolar cells (AT2) in the Asian sample reported by Yu Zhao et al. We further detected 2019-nCoV by polymerase chain reaction (PCR) from the nasal-swab and throat-swab of seven suspected cases. We found that 2019-nCoV tends to have a higher concentration in the nasal-swab comparing to the throat-swab, which could attribute to the ACE2-expressing nasal epithelial cells. We hope this study could be informative for virus-prevention strategy development, especially the treatment of nasal mucus.</jats:p>",2020-02-13,"['CHAO WU', 'Shufa Zheng', 'Yu Chen', 'Min Zheng']",,,,True
a726e1844e86c7c17b8b4461dd4c29ad3094c792,medrxiv,"Lockdown may partially halt the spread of 2019 novel coronavirus in Hubei province, China",doi.org/10.1101/2020.02.11.20022236,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>We present a timely evaluation of the impact of lockdown on the 2019-nCov epidemic in Hubei province, China. The implementation appears to be effective in reducing about 60% of new infections and deaths, and its effect also appears to be sustainable even after its removal. Delaying its implementation reduces its effectiveness. However, the direct economic cost of such a lockdown remains to be seen and whether the model is replicable in other Chinese regions remains a matter of further investigation.</jats:p>",2020-02-13,"['Mingwang Shen', 'Zhihang Peng', 'Yuming Guo', 'Yanni Xiao', 'Lei Zhang']",,,,True
d3c2e2839498c613ee95739dce7052109750362c,medrxiv,Long-Term Persistence of IgG Antibodies in SARS-CoV Infected Healthcare Workers,doi.org/10.1101/2020.02.12.20021386,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>BACKGROUND: The ongoing worldwide outbreak of the 2019-nCoV is markedly similar to the severe acute respiratory syndrome (SARS) outbreak 17 years ago. During the 2002-2003 SARS outbreak, healthcare workers formed a special population of patients. Although virus-specific IgG play important roles in virus neutralization and prevention against future infection, limited information is available regarding the long term persistence of IgG after infection with SARS-like coronavirus.  METHODS: A long-term prospective cohort study followed 34 SARS-CoV-infected healthcare workers from a hospital with clustered infected cases during the 2002-2003 SARS outbreak in Guangzhou, China, with a 13-year follow-up. Serum samples were collected annually from 2003-2015. Twenty SARS-CoV-infected and 40 non-infected healthcare workers were enrolled in 2015, and their serum samples were collected. All sera were tested for IgG antibodies with ELISA using whole virus and a recombinant nucleocapsid protein of SARS-CoV, as a diagnostic antigen. RESULTS: Anti SARS-CoV IgG was found to persist for up to 12 years. IgG titers typically peaked in 2004, declining rapidly from 2004-2006, and then continued to decline at a slower rate. IgG titers in SARS-CoV-infected healthcare workers remained at a significantly high level until 2015. Patients treated with corticosteroids at the time of infection were found to have lower IgG titers than those without. CONCLUSIONS: IgG antibodies against SARS-CoV can persist for at least 12 years. The presence of SARS-CoV IgG might provide protection against SARS-CoV and other betacoronavirus. This study provides valuable information regarding humoral immune responses against SARS-CoV and the 2019-nCoV.</jats:p>",2020-02-14,"['Xiaoqin Guo', 'Zhongmin Guo', 'Chaohui Duan', 'Zeliang chen', 'Guoling Wang', 'Yi Lu', 'Mengfeng Li', 'Jiahai Lu']",,,,True
d34a47b592e9c6e84b5b4115474349acbc0fb925,medrxiv,Statistics based predictions of coronavirus 2019-nCoV spreading in mainland China,doi.org/10.1101/2020.02.12.20021931,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background.  The epidemic outbreak cased by coronavirus 2019-nCoV is of great interest to researches because of the high rate of spread of the infection and the significant number of fatalities. A detailed scientific analysis of the phenomenon is yet to come, but the public is already interested in the questions of the duration of the epidemic, the expected number of patients and deaths. For long time predictions, the complicated mathematical models are necessary which need many efforts for unknown parameters identification and calculations. In this article, some preliminary estimates will be presented.        Objective. Since the reliable long time data are available only for mainland China, we will try to predict the epidemic characteristics only in this area. We will estimate some of the epidemic characteristics and present the most reliable dependences for victim numbers, infected and removed persons versus time.  Methods. In this study we use the known SIR model for the dynamics of an epidemic, the known exact solution of the linear equations and statistical approach developed before for investigation of the children disease, which occurred in Chernivtsi (Ukraine) in 1988-1989.    Results. The optimal values of the SIR model parameters were identified with the use of statistical approach. The numbers of infected, susceptible and removed persons versus time were predicted.   Conclusions. Simple mathematical model was used to predict the characteristics of the epidemic caused by coronavirus 2019-nCoV in mainland China. The further research should focus on updating the predictions with the use of fresh data and using more complicated mathematical models.</jats:p>",2020-02-13,['Igor Nesteruk'],,,,True
5fb2cce255dd56b944ae52cec664bd7f4f222c66,medrxiv,Estimating the daily trend in the size of the COVID-19 infected population in Wuhan,doi.org/10.1101/2020.02.12.20022277,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>There has been an outbreak of coronavirus disease (COVID-19) in Wuhan city, Hubei province, China since December 2019. Cases have been exported to other parts of China and more than 20 countries. We provide estimates of the daily trend in the size of the epidemic in Wuhan based on detailed information of 10,940 confirmed cases outside Hubei province.</jats:p>",2020-02-13,"['Qiushi Lin', 'Taojun Hu', 'Xiao-Hua Zhou']",,,,True
5585d267f9b505b068f9f72bff5f12c248472f0a,medrxiv,Epidemic size of novel coronavirus-infected pneumonia in the Epicenter Wuhan: using data of five-countries' evacuation action,doi.org/10.1101/2020.02.12.20022285,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Since late December 2019, novel coronavirus-infected pneumonia (NCP) emerged in Wuhan, Hubei province, China. Meanwhile, NCP rapidly spread from China to other countries, and several countries' government rush to evacuate their citizens from Wuhan. We analyzed the infection rate of the evacuees and extrapolated the results in Wuhan's NCP incidence estimation. Methods: We collected the total number and confirmed cases of 2019-nCov infection in the evacuation of Korea, Japan, Germany, Singapore, and France and estimated the infection rate of the 2019 novel coronavirus (2019-nCov) among people who were evacuated from Wuhan with a meta-analysis. NCP incidence of Wuhan was indirectly estimated based on data of evacuation.  Results: From Jan 29 to Feb 2, 2020, 1916 people have been evacuated from Wuhan, among them 17 have been confirmed 2019-nCov infected. The infection rate is estimated to be 1.1% (95% CI 0.4%-3.1%) using one group meta-analysis method with random effect model. We then estimated that almost 110,000 (95% CI: 40,000-310,000) people were infected with 2019-nCov in Wuhan around Feb 2, 2020, assuming the infection risk of evacuees is close to Chinese citizens in Wuhan. Conclusions: At the beginning of the outbreak, incidence of NCP may be vastly underestimated. Our result emphasizes that 2019-nCov has proposed a huge public health threats in Wuhan. We need to respond more rapidly, take large-scale public health interventions and draconian measures to limiting population mobility and control the epidemic.</jats:p>",2020-02-13,"['Hongxin Zhao', 'Sailimai Man', 'Bo Wang', 'Yi Ning']",,,,True
8f1e364cd0425a89dd61681571f8d3acc4d500d1,medrxiv,Clinical diagnosis of 8274 samples with 2019-novel coronavirus in Wuhan,doi.org/10.1101/2020.02.12.20022327,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background:  2019-Novel coronavirus (2019-nCoV) outbreaks create challenges for hospital laboratories because thousands of samples must be evaluated each day. Sample types, interpretation methods, and corresponding laboratory standards must be established. The possibility of other infections should be assessed to provide a basis for clinical classification, isolation, and treatment. Accordingly, in the present study, we evaluated the testing methods for 2019-nCoV and co-infections. Methods:  We used a fluorescence-based quantitative PCR kit urgently distributed by the Chinese CDC to detect 8274 close contacts in the Wuhan region against two loci on the 2019-nCoV genome. We also analyzed 613 patients with fever who underwent multiple tests for 13 respiratory pathogens; 316 subjects were also tested for 2019-nCoV. Findings:  Among the 8274 subjects, 2745 (33.2%) had 2019-nCoV infection; 5277 (63.8%) subjects showed negative results in the 2019-nCoV nucleic acid test (non-019-nCoV); and 252 cases (3.0%) because only one target was positive, the diagnosis was not definitive. Sixteen patients who originally had only one positive target were re-examined a few days later; 14 patients (87.5%) were finally defined as 2019-nCoV-positive, and 2 (12.5%) were finally defined as negative. The positive rates of nCoV-NP and nCovORF1ab were 34.7% and 34.7%, respectively. nCoV-NP-positive only and nCovORF1ab-positive cases accounted for 1.5% and 1.5%, respectively. In the 316 patients with multiple respiratory pathogens, 104 were positive for 2019-nCov and 6/104 had co-infection with coronavirus (3/104), influenza A virus (2/104), rhinovirus (2/104), and influenza A H3N2 (1/104); the remaining 212 patients had influenza A virus (11/202), influenza A H3N2 (11/202), rhinovirus (10/202), respiratory syncytial virus (7/202), influenza B virus (6/202), metapneumovirus (4/202), and coronavirus (2/202). Interpretation: Clinical testing methods for 2019-nCoV require improvement. Importantly, 5.8% of 2019-nCoV infected and 18.4% of non-2019-nCoV-infected patients had other pathogen infections. It is important to treat combined infections and perform rapid screening to avoid cross-contamination of patients. A test that quickly and simultaneously screens as many pathogens as possible is needed.</jats:p>",2020-02-13,"['Ming Wang', 'Qing Wu', 'Wanzhou Xu', 'Bin Qiao', 'Jingwei Wang', 'Hongyun Zheng', 'Shupeng Jiang', 'Junchi Mei', 'Zegang Wu', 'Yayun Deng', 'Fangyuan Zhou', 'Wei Wu', 'Yan Zhang', 'Zhihua Lv', 'Jingtao Huang', 'Xiaoqian Guo', 'Lina Feng', 'Zunen Xia', 'Di Li', 'Zhiliang Xu', 'Tiangang Liu', 'Pingan Zhang', 'Yongqing Tong', 'Yan Li']",,,,False
409c431edf54d022463f40f2d31a0dfab42f5324,medrxiv,Can Search Query Forecast successfully in China's 2019-nCov pneumonia?,doi.org/10.1101/2020.02.12.20022400,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Recently the novel coronavirus (2019-nCov) pneumonia outbreak in China then the world, and the Number of infections and death continues to increases. Search Query performs well in forecasting the epidemics. It is still a question whether search engine data can forecast the drift and the inflexion in 2019-nCov pneumonia. Based on the Baidu Search Index, we propose three prediction models: composite Index, composite Index with filtering and suspected NCP(Novel Coronavirus Pneumonia). The result demonstrates that the predictive model of composite index with filtering performs the best while the model of suspected NCP has the highest forecast error. We further predict the out-of-the-set NCP confirmed cases and monitor that the next peak of new diagnoses will occur on February 16th and 17th.</jats:p>",2020-02-18,"['Li Xiaoxuan', 'Wu Qi', 'Lv Benfu']",,,,True
c672f5b0d7c0a40f7cc1bdf079066d72eb8f64ec,medrxiv,ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection,doi.org/10.1101/2020.02.12.20022418,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>In December 2019 and January 2020, novel coronavirus (2019-nCoV) - infected pneumonia (NCIP) occurred in Wuhan, and has already posed a serious threat to public health. ACE2 (Angiotensin Converting Enzyme 2) has been shown to be one of the major receptors that mediate the entry of 2019-nCoV into human cells, which also happens in severe acute respiratory syndrome coronavirus (SARS). Several researches have indicated that some patients have abnormal renal function or even kidney damage in addition to injury in respiratory system, and the related mechanism is unknown. This arouses our interest in whether coronavirus infection will affect the urinary and male reproductive systems. Here in this study, we used the online datasets to analyze ACE2 expression in different human organs. The results indicate that ACE2 highly expresses in renal tubular cells, Leydig cells and cells in seminiferous ducts in testis. Therefore, virus might directly bind to such ACE2 positive cells and damage the kidney and testicular tissue of patients. Our results indicate that renal function evaluation and special care should be performed in 2019-nCoV patients during clinical work, because of the kidney damage caused by virus and antiviral drugs with certain renal toxicity. In addition, due to the potential pathogenicity of the virus to testicular tissues, clinicians should pay attention to the risk of testicular lesions in patients during hospitalization and later clinical follow-up, especially the assessment and appropriate intervention in young patients' fertility.</jats:p>",2020-02-13,"['Caibin Fan', 'Kai Li', 'Yanhong Ding', 'Wei Lu Lu', 'Jianqing Wang']",,,,True
11f96d05db6854ef95312aa3a4736724ce1f02d6,medrxiv,Interventions targeting air travellers early in the pandemic may delay local outbreaks of SARS-CoV-2,doi.org/10.1101/2020.02.12.20022426,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: We evaluated if interventions aimed at air travellers can delay establishment of a SARS-CoV-2 outbreak in a previously unaffected country.  Methods: For countries with no sustained SARS-CoV-2 transmission and with no shared border with affected regions we simulated arriving infected air travellers. We assessed the effectiveness of syndromic screening at departure and/or arrival &amp; traveller sensitisation to the COVID-2019-like symptoms with the aim to trigger rapid self-isolation and reporting on symptom onset to enable contact tracing. We assumed that syndromic screening would reduce the number of infected arrivals and that traveller sensitisation reduce the average number of secondary cases. We report the minimal expected delay achievable in 50% (75% &amp; 97.5%) of simulations. In the simulations we account for uncertainty in the number of secondary cases in the absence of air traveller targeted interventions and the arrival times of infected cases and also present sensitivity analyses on arrival rates of infected travellers and the effectiveness of traveller sensitisation. Results: Under baseline assumptions exit and entry screening combined with traveller sensitisation can delay a local SARS-CoV-2 outbreak by at least 83 (75% of simulations: at least 36, 97.5% 8) days while there is no more than 1 infected traveller per week. The benefit of entry screening is small if exit screening is effective: the combination of only exit screening and traveller sensitisation can delay an outbreak by at least 76 (75%: 33, 97.5%: 7) days. With increasing rates of infected travellers, less effective sensitisation or without screening these delays shrink rapidly to a week or less. Conclusion: Syndromic screening and traveller sensitisation in combination could delay outbreaks in yet unaffected countries and support local containment efforts, but only if infected traveller numbers are very low.</jats:p>",2020-02-13,,,,,True
aa13831b8a93267215d369c250da28f78e323203,medrxiv,"Early epidemiological assessment of the transmission potential and virulence of coronavirus disease 2019 (COVID-19) in Wuhan City: China, January-February, 2020",doi.org/10.1101/2020.02.12.20022434,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background:  Since the first cluster of cases was identified in Wuhan City, China, in December, 2019, coronavirus disease 2019 (COVID-19) has rapidly spread across China, causing multiple introductions in 109 countries/territories/areas as of March 10th. Despite the scarcity of publicly available data, scientists around the world have made strides in estimating the magnitude of the epidemic, the basic reproduction number, and transmission patterns. Recently more evidence suggests that a substantial fraction of the infected individuals with the novel coronavirus show little if any symptoms, which suggest the need to reassess the transmission potential of this emerging disease. In this study, we derive estimates of the transmissibility and virulence of COVID-19 in Wuhan City, China, by reconstructing the underlying transmission dynamics using multiple data sources. Methods:  We employ statistical methods and publicly available epidemiological datasets to jointly derive estimates of transmissibility and severity associated with the novel coronavirus. For this purpose, the daily series of laboratory-confirmed COVID-19 cases and deaths in Wuhan City and epidemiological data of Japanese evacuees from Wuhan City on board government-chartered flights were integrated into our analysis. Results:  Our posterior estimates of basic reproduction number (R) in Wuhan City, China in 2019-2020 reached values as high as 5.20 (95%CrI: 5.04-5.47) and the enhanced public health intervention after January 23rd in 2020 was associated with a declined R at 0.58 (95%CrI: 0.51-0.64), with the total number of infections (i.e. cumulative infections) estimated at 1905526 (95%CrI: 1350283-2655936) in Wuhan City, raising the proportion of infected individuals to 19.1% (95%CrI: 13.5-26.6%). We also found that most recent crude infection fatality ratio (IFR) and time-delay adjusted IFR is estimated to be 0.04% (95% CrI: 0.03-0.06%) and 0.12% (95%CrI: 0.08-0.17%), which is several orders of magnitude smaller than the crude CFR estimated at 4.19% Conclusions:  We have estimated key epidemiological parameters of the transmissibility and virulence of COVID-19 in Wuhan, China during January-February, 2020 using an ecological modelling approach. The power of our approach lies in the ability to infer epidemiological parameters with quantified uncertainty from partial observations collected by surveillance systems.</jats:p>",2020-02-13,"['Kenji Mizumoto', 'Katsushi Kagaya', 'Gerardo Chowell']",,,,False
90b5ecf991032f3918ad43b252e17d1171b4ea63,medrxiv,The role of absolute humidity on transmission rates of the COVID-19 outbreak,doi.org/10.1101/2020.02.12.20022467,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>A novel coronavirus (COVID-19) was identified in Wuhan, Hubei Province, China, in December 2019 and has caused over 40,000 cases worldwide to date. Previous studies have supported an epidemiological hypothesis that cold and dry (low absolute humidity) environments facilitate the survival and spread of droplet-mediated viral diseases, and warm and humid (high absolute humidity) environments see attenuated viral transmission (i.e., influenza). However, the role of absolute humidity in transmission of COVID-19 has not yet been established. Here, we examine province-level variability of the basic reproductive numbers of COVID-19 across China and find that changes in weather alone (i.e., increase of temperature and humidity as spring and summer months arrive in the North Hemisphere) will not necessarily lead to declines in COVID-19 case counts without the implementation of extensive public health interventions.</jats:p>",2020-02-17,"['Wei Luo', 'Maimuna S Majumder', 'Dianbo Liu', 'Canelle Poirier', 'Kenneth D Mandl', 'Marc Lipsitch', 'Mauricio Santillana']",,,,True
05d99c07db59b6948e39bfa62c2cbbf62944059a,medrxiv,A spatial model of CoVID-19 transmission in England and Wales: early spread and peak timing,doi.org/10.1101/2020.02.12.20022566,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: An outbreak of a novel coronavirus, named CoVID-19, was first reported in China on 31 December 2019. As of 9 February 2020, cases have been reported in 25 countries, including probable cases of human-to-human transmission in England.    Methods: We adapted an existing national-scale metapopulation model to capture the spread of CoVID-19 in England and Wales. We used 2011 census data to capture population sizes and population movement, together with parameter estimates from the current outbreak in China.   Results:  We predict that a CoVID-19 outbreak will peak 126 to 147 days (~4 months) after the start of person-to-person transmission in England and Wales in the absence of controls, assuming biological parameters remain unchanged. Therefore, if person-to-person transmission persists from February, we predict the epidemic peak would occur in June. The starting location has minimal impact on peak timing, and model stochasticity varies peak timing by 10 days. Incorporating realistic parameter uncertainty leads to estimates of peak time ranging from 78 days to 241 days after person-to-person transmission has been established.  Seasonal changes in transmission rate substantially impact the timing and size of the epidemic peak, as well as the total attack rate.   Discussion: We provide initial estimates of the potential course of CoVID-19 in England and Wales in the absence of control measures. These results can be refined with improved estimates of epidemiological parameters, and permit investigation of control measures and cost effectiveness analyses. Seasonal changes in transmission rate could shift the timing of the peak into winter months, which will have important implications for healthcare capacity planning.</jats:p>",2020-02-14,"['Leon Danon', 'Ellen Brooks-Pollock', 'Mick Bailey', 'Matt J Keeling']",,,,True
38bab3f17b186bd8ee289e5d135bb7d500ef500b,medrxiv,Probabilistic reconstruction of measles transmission clusters from routinely collected surveillance data,doi.org/10.1101/2020.02.13.20020891,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Pockets of susceptibility resulting from spatial or social heterogeneity in vaccine coverage can drive measles outbreaks, as cases imported into such pockets are likely to cause further transmission and lead to large transmission clusters. Characterising the dynamics of transmission is essential for identifying which individuals and regions might be most at risk.  As data from detailed contact tracing investigations are not available in many settings, we combined age, location, genotype, and onset date of cases in order to probabilistically reconstruct the importation status and transmission clusters within a newly developed R package called o2geosocial.   We compared our inferred cluster size distributions to 737 transmission clusters identified through detailed contact-tracing in the United States between 2001 and 2016. We were able to reconstruct the importation status of the cases and found good agreement between the inferred and reference clusters. The results were improved when the contact-tracing investigations were used to set the importation status before running the model.  Spatial heterogeneity in vaccine coverage is difficult to measure directly. Our approach was able to highlight areas with potential for local transmission using a minimal number of variables and could be applied to assess the intensity of ongoing transmission in a region.</jats:p>",2020-02-15,"['Alexis Robert', 'Adam J Kucharski', 'Paul A Gastañaduy', 'Prabasaj Paul', 'Sebastian Funk']",,,,True
7ed2c0786eef3d39fa0435b461aa34ab454a4753,medrxiv,Understanding the present status and forecasting of COVID―19 in Wuhan,doi.org/10.1101/2020.02.13.20022251,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The present status of COVID―19 is analyzed and the end of the disease is forecasted. The peak of the epidemic is different in three regions, Wuhan, Hubei province except Wuhan, and mainland China except Hubei. In two regions except Wuhan, the peak of the epidemic passed ten days ago. If the trend until February 11 does not change, the disease may end by the end of February. In Wuhan, the epidemic reached a peak but the reported number of newly infected patients fluctuates largely. We need to know the reason for the big fluctuation to forecast the end of the disease.</jats:p>",2020-02-14,['Toshihisa Tomie'],,,,True
8b71ce92ec03e066eca7792bfd17e2f210d50ce3,medrxiv,"Optimizing diagnostic strategy for novel coronavirus pneumonia, a multi-center study in Eastern China",doi.org/10.1101/2020.02.13.20022673,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>COVID-19 caused by a novel coronavirus SARS-CoV-2 emerged in Wuhan, Hubei province since December 2019, and caused a rapid outbreak throughout China and globally. Cities outside Hubei are also facing great challenge and require implementing of effective and feasible strategy in precision diagnosing novel coronavirus pneumonia (NCP).  We described a multicenter prospective study on diagnostic strategy of suspected NCP patients from January 22nd to February 9th, 2020 in Eastern China cities. Nasopharyngeal swabs were collected from the patients. The epidemiological characteristics, clinical symptoms, laboratory assessments, and computed tomographic (CT) scans were obtained. Pathogen screen were performed including RT-PCR, multiplex PCR, rapid flu antigen tests and mNGS.  We enrolled 53 suspected NCP patients, among whom 20 were laboratory-confirmed. Fourteen (70%) and 3 (15%) patients were positive for the first and second SARS-CoV-2 RT-PCR test, respectively. All NCP patients were positive for mNGS. Chest CT images and the symptoms of early stage NCP patients were similar to other viral pneumonia patients. We identified 11 of 20 co-infections in NCP cases, including regular respiratory virus, fungi and bacteria synchronously. Genomic analysis showed that 8 of 10 cases had no mutation in virus genome, while 2 cases had only one single mutation in N gene.  Our study discovered that a combination of chest CT, SARS-CoV-2 RT-PCR and multi-plex PCR is recommended in regions outside Hubei province. Co-infection of other pathogens with SARS-CoV-2 exists and should be acknowledged. Repeated sampling, change of specimen type or metagenomics sequencing could further facilitate during critical clinical cases.</jats:p>",2020-02-17,"['Jing-Wen Ai', 'Hao-Cheng Zhang', 'Teng Xu', 'Jing Wu', 'Mengqi Zhu', 'Yi-Qi Yu', 'Han-Yue Zhang', 'Zhongliang Shen', 'Yang Li', 'Xian Zhou', 'Guo-Qing Zang', 'Jie Xu', 'Wen-Jing Chen', 'Yong-Jun Li', 'De-Sheng Xie', 'Ming-Zhe Zhou', 'Jing-Ying Sun', 'Jia-Zhen Chen', 'Wen-Hong Zhang']",,,,True
adb3a6501ad731eda95d0a1a182a793a0dcd58b0,medrxiv,"Quantifying bias of COVID-19 prevalence and severity estimates in Wuhan, China that depend on reported cases in international travelers",doi.org/10.1101/2020.02.13.20022707,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Risk of COVID-19 infection in Wuhan has been estimated using imported case counts of international travelers, often under the assumption that all cases in travelers are ascertained. Recent work indicates variation among countries in detection capacity for imported cases. Singapore has historically had very strong epidemiological surveillance and contact-tracing capacity and has shown in the COVID-19 epidemic evidence of a high sensitivity of case detection. We therefore used a Bayesian modeling approach to estimate the relative imported case detection capacity for other countries compared to that of Singapore. We estimate that the global ability to detect imported cases is 38% (95% HPDI 22% - 64%) of Singapore′s capacity. Equivalently, an estimate of 2.8 (95% HPDI 1.5 - 4.4) times the current number of imported cases, could have been detected, if all countries had had the same detection capacity as Singapore. Using the second component of the Global Health Security index to stratify likely case-detection capacities, we found that the ability to detect imported cases relative to Singapore among high surveillance locations is 40% (95% HPDI 22% -  67%), among intermediate surveillance locations it is 37% (95% HPDI 18% - 68%), and among low surveillance locations it is 11% (95% HPDI 0% - 42%). Using a simple mathematical model, we further find that treating all travelers as if they were residents (rather than accounting for the brief stay of some of these travelers in Wuhan) can modestly contribute to underestimation of prevalence as well. We conclude that estimates of case counts in Wuhan based on assumptions of perfect detection in travelers may be underestimated by several fold, and severity correspondingly overestimated by several fold. Undetected cases are likely in countries around the world, with greater risk in countries of low detection capacity and high connectivity to the epicenter of the outbreak.</jats:p>",2020-02-14,"['Rene Niehus', 'Pablo M De Salazar', 'Aimee Taylor', 'Marc Lipsitch']",,,,True
790594df61d9f88e8e99e2e135141e4b2ff3e8b7,medrxiv,Analysis of meteorological conditions and prediction of epidemic trend of 2019-nCoV infection in 2020,doi.org/10.1101/2020.02.13.20022715,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: To investigate the meteorological condition for incidence and spread of 2019-nCoV infection, to predict the epidemiology of the infectious disease, and to provide a scientific basis for prevention and control measures against the new disease.  Methods: The meteorological factors during the outbreak period of the novel coronavirus pneumonia in Wuhan in 2019 were collected and analyzed, and were confirmed with those of Severe Acute Respiratory Syndrome (SARS) in China in 2003. Data of patients infected with 2019-nCoV and SARS coronavirus were collected from WHO website and other public sources. Results: This study found that the suitable temperature range for 2019-nCoV coronavirus survival is (13-24 degree Celsius), among which 19 degree Celsius lasting about 60 days is conducive to the spread between the vector and humans; the humidity range is 50%-80%, of which about 75% humidity is conducive to the survival of the coronavirus; the suitable precipitation range is below 30 mm/ month. Cold air and continuous low temperature over one week are helpful for the elimination of the virus. The prediction results show that with the approach of spring, the temperature in north China gradually rises, and the coronavirus spreads to middle and high latitudes along the temperature line of 13-18 degree Celsius. The population of new coronavirus infections is concentrated in Beijing, Tianjin, Hebei, Jiangsu, Zhejiang, Shanghai and other urban agglomerations. Starting from May 2020, the Beijing-Tianjin-Hebei urban agglomeration, the Central China Zhengzhou-Wuhan urban agglomeration, the eastern Jiangsu-Zhejiang-Shanghai urban agglomeration, and the southern Pearl River Delta urban agglomeration are all under a high temperature above 24 degree Celsius, which is not conducive to the survival and reproduction of coronaviruses, so the epidemic is expected to end. Conclusions: A wide range of continuous warm and dry weather is conducive to the survival of 2019-nCoV. The coming of spring, in addition to the original Wuhan-Zhengzhou urban agglomeration in central China, means that the prevention and control measures in big cities located in mid-latitude should be strengthened, especially the monitoring of transportation hubs. The Pearl River Delta urban agglomeration is a concentrated area of population in south China, with a faster temperature rise than those in mid-high latitudes, and thus the prevention in this area should be prioritized. From a global perspective, cities with a mean temperature below 24 degree Celsius are all high-risk cities for 2019-nCoV transmission before June.</jats:p>",2020-02-18,"['Jin Bu', 'Dong-Dong Peng', 'Hui Xiao', 'Qian Yue', 'Yan Han', 'Yu Lin', 'Gang Hu', 'Jing Chen']",,,,False
1218f278a4f8d83dac14b23c8f698062812ef9d5,medrxiv,Potential impact of seasonal forcing on a SARS-CoV-2 pandemic,doi.org/10.1101/2020.02.13.20022806,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 80,000 confirmed infections and 2,700 fatalities (as of Feb 27, 2020). Imported cases and transmission clusters of various sizes have been reported globally suggesting a pandemic is likely. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterize our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.</jats:p>",2020-02-17,"['Richard A Neher', 'Robert Dyrdak', 'Valentin Druelle', 'Emma B Hodcroft', 'Jan Albert']",,,,True
8561c93ff9ef748db062c58de9477bf7dc57c1ad,medrxiv,"Estimating the distribution of the incubation period of 2019 novel coronavirus (COVID-19) infection between travelers to Hubei, China and non-travelers",doi.org/10.1101/2020.02.13.20022822,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objectives: Amid the continuing spread of the novel coronavirus (COVID-19), the incubation period of COVID-19 should be regularly re-assessed as more information is available upon the increase in reported cases. The present work estimated the distribution of incubation periods of patients infected in and outside Hubei province of China.  Methods: Clinical data were collected from the individual cases reported by the media as they were not fully available on the official pages of the Chinese health authorities. MLE was used to estimate the distributions of the incubation period. Results: It was found that the incubation period of patients with no travel history to Hubei was longer and more volatile. Conclusion: It is recommended that the duration of quarantine should be extended to at least 3 weeks.</jats:p>",2020-02-18,['Char Leung'],,,,False
47b07518dc0f608e53198bb5f8a95caa1c164fe5,medrxiv,A simple laboratory parameter facilitates early identification of COVID-19 patients,doi.org/10.1101/2020.02.13.20022830,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The total number of COVID-19 patients since the outbreak of this infection in Wuhan, China has reached 40000 and are still growing. To facilitate triage or identification of the large number of COVID-19 patients from other patients with similar symptoms in designated fever clinics, we set to identify a practical marker that could be conveniently utilized by first-line health-care workers in clinics. To do so, we performed a case-control study by analyzing clinical and laboratory findings between PCR-confirmed SARS-CoV-2 positive patients (n=52) and SARS-CoV-2 negative patients (n=53). The patients in two cohorts all had similar symptoms, mainly fever and respiratory symptoms. The rates of patients with leukocyte counts (normal or decreased number) or lymphopenia (two parameters suggested by current National and WHO COVID-19 guidelines) had no differences between these two cohorts, while the rate of eosinopenia (decreased number of eosinophils) in SARS-CoV-2 positive patients (79%) was much higher than that in SARS-CoV-2 negative patients (36%). When the symptoms were combined with eosinopenia, this combination led to a diagnosis sensitivity and specificity of 79% and 64%, respectively, much higher than 48% and 53% when symptoms were combined with leukocyte counts (normal or decreased number) and/ or lymphopenia. Thus, our analysis reveals that eosinopenia may be a potentially more reliable laboratory predictor for SARS-CoV-2 infection than leukocyte counts and lymphopenia recommended by the current guidelines.</jats:p>",2020-02-17,"['Qilin Li', 'Xiuli Ding', 'Geqing Xia', 'Zhi Geng', 'Fenghua Chen', 'Lin Wang', 'Zheng Wang']",,,,True
5fd9e85742633591d7eb5792f0e06ff33792d4a1,medrxiv,Clinical Characteristics of 2019 Novel Infected Coronavirus Pneumonia：A Systemic Review and Meta-analysis,doi.org/10.1101/2020.02.14.20021535,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background:A Novel pneumonia associated with the 2019 coronavirus infected pneumonia (NCIP) suddenly broke out in Wuhan, China in December 2019. 37287 confirmed cases and 813 death case in China (Until 8th/Feb/2019) have been reported in just fortnight. Although this risky pneumonia with high infection rates and high mortality rates need to be resolved immediately, major gaps in our knowledge of clinical characters of it were still not be established. The aim of this study is to summaries and analysis the clinical characteristics of 2019-nCoV pneumonia. Methods: Literature have been systematically performed a search on PubMed, Embase, Web of Science, GreyNet International, and The Cochrane Library from inception up to February 8, 2020. The Newcastle-Ottawa Scale was used to assess quality, and publication bias was analyzed by Egger test. In the single-arm meta-analysis, A fix-effects model was used to obtain a pooled incidence rate. We conducted subgroup analysis according to geographic region and research scale. Results: A total of nine studies including 356 patients were included in this study, the mean age was 52.4 years and 221 (62.1%) were male. The pooled incidences rate of symptoms as follows: pharyngalgia (12.2%, 95% CI: 0.087-0.167), diarrhea (9.2%, 95% CI: 0.062-0.133) and headache (8.9%, 95% CI: 0.063-0.125). Meanwhile, 5.7% (95% CI: 0.027-0.114) of patients were found without any symptoms although they were diagnosed by RT-PCR. In the terms of CT imaging examination, the most of patients showed bilateral mottling or ground-glass opacity, 8.6% (95% CI: 0.048-0.148) of patients with crazy-paving pattern, and 11.5% (95% CI: 0.064-0.197) of patients without obvious CT imaging presentations. The pooled incidence of mortality was 8.9% (95% CI: 0.062-0.126). Conclusions: To our knowledge, this is the first evidence-based medicine research to further elaborate the clinical characteristics of NCIP, which is beneficial to the next step of prevention and treatment.</jats:p>",2020-02-17,"['Kai Qian', 'Yi Deng', 'Yonghang Tai', 'Jun Peng', 'Hao Peng', 'Lihong Jiang']",,,,False
f4d76fb8161f4cee6987d7d412798e1276348858,medrxiv,Assessing the impact of reduced travel on exportation dynamics of novel coronavirus infection (COVID-19),doi.org/10.1101/2020.02.14.20022897,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The impact of the drastic reduction in travel volume within mainland China in January and February 2020 was quantified with respect to reports of novel coronavirus (COVID-19) infections outside China. Data on confirmed cases diagnosed outside China were analyzed using statistical models to estimate the impact of travel reduction on three epidemiological outcome measures: (i) the number of exported cases, (ii) the probability of a major epidemic, and (iii) the time delay to a major epidemic. From 28 January to 7 February 2020, we estimated that 226 exported cases (95% confidence interval: 86, 449) were prevented, corresponding to a 70.4% reduction in incidence compared to the counterfactual scenario. The reduced probability of a major epidemic ranged from 7% to 20% in Japan, which resulted in a median time delay to a major epidemic of two days. Depending on the scenario, the estimated delay may be less than one day. As the delay is small, the decision to control travel volume through restrictions on freedom of movement should be balanced between the resulting estimated epidemiological impact and predicted economic fallout.</jats:p>",2020-02-17,"['Asami Anzai', 'Tetsuro Kobayashi', 'Natalie M. Linton', 'Ryo Kinoshita', 'Katsuma Hayashi', 'Ayako Suzuki', 'Yichi Yang', 'Sungmok Jung', 'Takeshi Miyama', 'Andrei R. Akhmetzhanov', 'Hiroshi Nishiura']",,,,True
b1b9d81726e56c2781ce6b63ae5015cf2f314c6f,medrxiv,Estimating the Efficacy of Traffic Blockage and Quarantine for the Epidemic Caused by 2019-nCoV (COVID-19),doi.org/10.1101/2020.02.14.20022913,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Since the 2019-nCoV (COVID-19) outbreaks in Wuhan, China, the cumulative number of confirmed cases is increasing every day, and a large number of populations all over the world are at risk. The quarantine and traffic blockage can alleviate the risk of the epidemic and the infections, henceforth evaluating the efficacy of such actions is essential to inform policy makers and raise the public awareness of the importance of self-isolation and quarantine.  Method: We collected confirmed case data and the migration data, and introduced the quarantine factor and traffic blockage factor to the Flow-SEIR model. By varying the quarantine factor and traffic blockage factor, we simulated the change of the peak number and arrival time of infections, then the efficacy of these two intervation measures can be analyzed in our simulation. In our study,  the self-protection at home is also included in quarantine.  Results: In the simulated results, the quarantine and traffic blockage are effective for epidemic control. For Hubei province, the current quarantine factor is estimaed to be 0.405, which means around 40.5% of suceptibles who are close contacting with are in quarantine, and the current traffic blockage factor is estimaed to be 0.66, which indicates around 34% of suceptibles who had flowed out from Hubei. For the other provinces outside Hubei, the current quarantine factor is estimated to be 0.285, and the current traffic blockage factor is estimated to be 0.26. With the quarantine and traffic blockage factor increasing, the number of infections decrease dramatically. We also simulated the start dates of quarantine and traffic blockage at four time points, the simulated results show that the early of warning is also effective for epidemic containing. However, provincial level traffic blockage can only alleviate 21.06% - 22.38% of the peak number of infections. In general, the quarantine is much more effective than the traffic blockage control.   Conclusion: Both of quarantine and traffic blockage are effective ways to control the spread of COVID-19. However, the eff  icacy of quarantine is found to be much stronger than that of traffic blockage. Considering traffic blockage may also cause huge losses of economy, we propose to gradually deregulate the traffic blockage, and improve quarantine instead. Also, there might be a large number of asymptomatic carriers of COVID-19, the quarantine should be continued for a long time until the epidemic is totally under control.</jats:p>",2020-02-17,"['Deqiang Li', 'Zhicheng Liu', 'Qinghe Liu', 'Zefei Gao', 'Junkai Zhu', 'Junyan Yang', 'Qiao Wang']",,,,True
f4f4b045dce8ff5ff1f5aaa48a6bdbaaa7b05179,medrxiv,A new transmission route for the propagation of the SARS-CoV-2 coronavirus,doi.org/10.1101/2020.02.14.20022939,,,See https://www.medrxiv.org/submit-a-manuscript,<jats:p>We explore here how variation in the SARS-CoV-2 virus tropism could influence epidemic spread. We use a compartmental model fit to the existing data. The model indicates that Wuhan quarantine measures were effective but that alternative virus forms (gut tropism) and a second propagation route (through environment) was present. For Singapore and Shenzhen region the secondary route does not seem to be active yet. Adequate prevention measures taking into account both routes should be implemented.</jats:p>,2020-02-18,"['Antoine Danchin', 'Tuen Wai Patrick Ng', 'Gabriel TURINICI']",,,,True
4144f646c2005c781d7834d5950dc3490cd082d0,medrxiv,A deep learning algorithm using CT images to screen for Corona Virus Disease (COVID-19),doi.org/10.1101/2020.02.14.20023028,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>To control the spread of Corona Virus Disease (COVID-19), screening large numbers of suspected cases for appropriate quarantine and treatment is a priority. Pathogenic laboratory testing is the diagnostic gold standard but it is time consuming with significant false negative results. Fast and accurate diagnostic methods are urgently needed to combat the disease. Based on COVID-19 radiographical changes in CT images, we aimed to develop a deep learning method that could extract COVID-19's graphical features in order to provide a clinical diagnosis ahead of the pathogenic test, thus saving critical time for disease control.  Methods:We collected 1,119 CT images of pathogen-confirmed COVID-19 cases along with those previously diagnosed with typical viral pneumonia. We modified the Inception transfer-learning model to establish the algorithm, followed by internal and external validation.  Results: The internal validation achieved a total accuracy of 89.5% with specificity of 0.88 and sensitivity of 0.87. The external testing dataset showed a total accuracy of 79.3% with specificity of 0.83 and sensitivity of 0.67. In addition, in 54 COVID-19 images that first two nucleic acid test results were negative, 46 were predicted as COVID-19 positive by the algorithm, with the accuracy of 85.2%. Conclusion: These results demonstrate the proof-of-principle for using artificial intelligence to extract radiological features for timely and accurate COVID-19 diagnosis.</jats:p>",2020-02-17,"['Shuai Wang', 'Bo Kang', 'Jinlu Ma', 'Xianjun Zeng', 'Mingming Xiao', 'Jia Guo', 'Mengjiao Cai', 'Jingyi Yang', 'Yaodong Li', 'Xiangfei Meng', 'Bo Xu']",,,,True
f7891683eecd12b3908862fc7ef1d341ca7a293c,medrxiv,The Efficacy of Contact Tracing for the Containment of the 2019 Novel Coronavirus (COVID-19).,doi.org/10.1101/2020.02.14.20023036,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Contact tracing is a central public health response to infectious disease outbreaks, especially in the early stages of an outbreak when specific treatments are limited. Importation of novel Coronavirus (COVID-19) from China and elsewhere into the United Kingdom highlights the need to understand the impact of contact tracing as a control measure. Using detailed survey information on social encounters coupled to predictive models, we investigate the likely efficacy of the current UK definition of a close contact (within 2 meters for 15 minutes or more) and the distribution of secondary cases that may go untraced. Taking recent estimates for COVID-19 transmission, we show that less than 1 in 5 cases will generate any subsequent untraced cases, although this comes at a high logistical burden with an average of 36.1 individuals (95th percentiles 0-182) traced per case. Changes to the definition of a close contact can reduce this burden, but with increased risk of untraced cases; we estimate that any definition where close contact requires more than 4 hours of contact is likely to lead to uncontrolled spread.</jats:p>",2020-02-17,"['Matt J Keeling', 'T. Deirdre Hollingsworth', 'Jonathan M Read']",,,,True
0eda8331214ca028350b07e2953702f3078a105e,medrxiv,Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (COVID-19),doi.org/10.1101/2020.02.14.20023127,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background Estimation of the fraction and contagiousness of undocumented novel coronavirus (COVID-19) infections is critical for understanding the overall prevalence and pandemic potential of this disease. Many mild infections are typically not reported and, depending on their contagiousness, may support stealth transmission and the spread of documented infection.   Methods Here we use observations of reported infection and spread within China in conjunction with mobility data, a networked dynamic metapopulation model and Bayesian inference, to infer critical epidemiological characteristics associated with the emerging coronavirus, including the fraction of undocumented infections and their contagiousness.   Results We estimate 86% of all infections were undocumented (95% CI: [82%-90%]) prior to the Wuhan travel shutdown (January 23, 2020). Per person, these undocumented infections were 52% as contagious as documented infections ([44%-69%]) and were the source of infection for two-thirds of documented cases. Our estimate of the reproductive number (2.23; [1.77-3.00]) aligns with earlier findings; however, after travel restrictions and control measures were imposed this number falls considerably. Conclusions A majority of COVID-19 infections were undocumented prior to implementation of control measures on January 23, and these undocumented infections substantially contributed to virus transmission. These findings explain the rapid geographic spread of COVID-19 and indicate containment of this virus will be particularly challenging. Our findings also indicate that heightened awareness of the outbreak, increased use of personal protective measures, and travel restriction have been associated with reductions of the overall force of infection; however, it is unclear whether this reduction will be sufficient to stem the virus spread.</jats:p>",2020-02-17,"['Ruiyun Li', 'Sen Pei', 'Bin Chen', 'Yimeng Song', 'Tao Zhang', 'Wan Yang', 'Jeffrey Shaman']",,,,True
57e01ad2a4961cd5cc6a3733f5f8c013a8946f3c,medrxiv,A model simulation study on effects of intervention measures in Wuhan COVID-19 epidemic,doi.org/10.1101/2020.02.14.20023168,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: In the beginning of January 2020, new unknown virus pneumonia cases started to emerge in local hospitals in Wuhan, China. This virus epidemic quickly became a public health emergency of international concern by the WHO. Enormous amount of medical supplies as well as healthcare personals from other provinces were mobilized to support Wuhan. This current work tent to help people understanding how infectious disease spread and the purpose and consequences of various efforts based on simulation model. Method: a simulation model was created using known parameters. R0 set to 3 and mean incubation time to be 7.5days. the epidemic was divided to 3 periods. Simulation would run 50 times to mimic different patient0 status. Personal activity index was used to mimic different level of control measures. 141427709 simulated patients were created. Cumulation number of patients at the end of period 1 (day50) is 2868.7 ± 1739.0. Total infected patients could be 913396.5 ± 559099.9 by the end of period 2 (day70) in free transmission state. And at day90, total patients number is 913396.5 ± 559099.9. Conclusion: COVID-19 is a novel severe respiratory disease. This will put great burden on the shoulder of healthcare workers as well as on medical hardware and supplements. Current strict control measures help to contain disease from spreading. An early detecting, reporting and fast reacting system needs to be setup to prevent future unknown infectious disease.</jats:p>",2020-02-18,"['Guopeng ZHOU', 'Chunhua CHI']",,,,True
b55fccac1406441d77e86c7cfabafc10bcc11505,medrxiv,Estimate number of individuals infected with the 2019-novel coronavirus in South Korea due to the influx of international students from countries with virus risk: a simulation study,doi.org/10.1101/2020.02.15.20023234,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: In March 2020, overall, 37,000 international students from the country at risk of the 2019-novel coronavirus (COVID-19) infection will arrive in Seoul, South Korea. Individuals from the country at risk of COVID-19 infection have been included in a home-quarantine program, but the efficacy of the program is uncertain. Methods: To estimate the possible number of infected individuals within the large influx of international students, we used a deterministic compartmental model for epidemic and perform a simulation-based search of different rates of compliance with home-quarantine. Results: Under the home-quarantine program, the total number of the infected individuals would reach 24-53 from March 17-March 20, 50-86 from March 18-March 16, and 234-343 from March 4-March 23 with the arrival of 0.1%, 0.2%, and 1% of pre-infectious individuals, in Seoul, South Korea, respectively. Our findings indicated when incoming international students showed strict compliance with quarantine, epidemics were less likely to occur in Seoul, South Korea.  Conclusion: To mitigate possible epidemics, additional efforts to improve the compliance of home-quarantine are warranted along with other containment policies.</jats:p>",2020-02-19,"['Sukhyun Ryu', 'Sheikh Taslim Ali', 'Jun-sik Lim', 'Byung Chul Chun']",,,,False
91098f6fe46a21565bf0cb06fe960cdb2c3f5e38,medrxiv,"The role of institutional trust in preventive and treatment-seeking behaviors during the 2019 novel coronavirus (2019-nCoV) outbreak among residents in Hubei, China",doi.org/10.1101/2020.02.15.20023333,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background Since December 2019, pneumonia associated with the 2019 novel coronavirus (2019-nCoV) has emerged in Wuhan, China. The exponential increase of the confirmed number of cases of 2019n-CoV is of great concern to the global community. The fears and panic among residents in the epicenters have prompted diverse responses, which are understudied. During such a crisis, community trust and support for the government and health authorities are important to contain the outbreak. We aimed to investigate the influence of institutional trust on public responses to the 2019-nCoV outbreak. Methods An anonymous Internet-based, cross-sectional survey was administered on  January 29, 2020. The study population comprised all residents currently residing or working in the province of Hubei, where Wuhan is the capital city. The level of trust in information provision and preventive instructions, individual preventive behaviors and treatment-seeking behaviors were queried. Findings The majority of the participants expressed a great extent of trust in the information and preventive instructions provided by the central government than by the local government. A high uptake of 2019-nCoV preventive measures was found, particularly among people who had been placed under quarantine. Being under quarantine (adjusted odds ratio [OR] = 2.35, 95% confidence interval [CI] 1.80 to 3.08) and having a high institutional trust score (OR = 2.23, 95% CI 1.96 to 2.53) were both strong and significant determinants of higher preventive behavior scores. The majority of study participants (85.7%, n = 3,640) reported that they would seek hospital treatment if they suspected themselves to have been infected with 2019 n-CoV. Few of the participants from Wuhan (16.6%, n = 475) and those participants who were under quarantine (13.8%, n = 550) expressed an unwillingness to seek hospital treatment. Similarly, being under quarantine (OR = 2.36, 95% CI 1.80 to 3.09) and having a high institutional trust score (OR = 2.20, 95% CI 1.96 to 2.49) were two strong significant determinants of hospital treatment-seeking.  Interpretation The results of this study suggest that institutional trust is an important factor influencing adequate preventive behavior and seeking formal medical care during an outbreak. In view of the 2019-nCoV being highly pathogenic and extremely contagious, our findings also underscore the importance of public health intervention to reach individuals with poor adherence to preventive measures and who are reluctant to seek treatment at formal health services. Funding National  Key  R&amp;D  Program  of  China, Ningbo Health Branding Subject Fund,   Sanming Project of Medicine in Shenzhen, K.C. Wong Magna Fund in Ningbo University, National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities,  China Postdoctoral Science Foundation, and Natural Science Basic Research Program of Shanxi Province. Keywords: 2019-nCoV;  institutional trust; preventive behaviors</jats:p>",2020-02-21,"['Li Ping Wong', 'Qun hong Wu', 'Xi Chen', 'Zhuo Chen', 'Haridah Alias', 'Mingwang Shen', 'Jing cen Hu', 'Shiwei Duan', 'Jin jie Zhang', 'Liyuan Han']",,,,True
317943dec06b88c1c62ef0ecd832f0d644b1d417,medrxiv,"Evaluating new evidence in the early dynamics of the novel coronavirus COVID-19 outbreak in Wuhan, China with real time domestic traffic and potential asymptomatic transmissions",doi.org/10.1101/2020.02.15.20023440,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The novel coronavirus (COVID-19), first detected in Wuhan, China in December 2019, has spread to 28 countries/regions with over 43,000 confirmed cases. Much about this outbreak is still unknown. At this early stage of the epidemic, it is important to investigate alternative sources of information to understand its dynamics and spread. With updated real time domestic traffic, this study aims to integrate recent evidence of international evacuees extracted from Wuhan between Jan. 29 and Feb. 2, 2020 to infer the dynamics of the COVD-19 outbreak in Wuhan. In addition, a modified SEIR model was used to evaluate the empirical support for the presence of asymptomatic transmissions. Based on the data examined, this study found little evidence for the presence of asymptomatic transmissions. However, it is still too early to rule out its presence conclusively due to sample size and other limitations. The updated basic reproductive number was found to be 2.12 on average with a 95% credible interval of [2.04, 2.18]. It is smaller than previous estimates probably because the new estimate factors in the social and non-pharmaceutical mitigation implemented in Wuhan through the evacuee dataset. Detailed predictions of infected individuals exported both domestically and internationally were produced. The estimated case confirmation rate has been low but has increased steadily to 23.37% on average. The findings of this study depend on the validity of the underlying assumptions, and continuing work is needed, especially in monitoring the current infection status of Wuhan residents.</jats:p>",2020-02-18,['Can Zhou'],,,,True
73998a3f565b661816d48aa7c20fa5ae617864d5,medrxiv,Profiling ACE2 expression in colon tissue of healthy adults and colorectal cancer patients by single-cell transcriptome analysis,doi.org/10.1101/2020.02.15.20023457,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>A newly identified novel coronavirus (2019-nCoV) has caused numerous acute respiratory syndrome cases in Wuhan China from December 2019 to Feb 2020. Its fast spreading to other provinces in China and overseas is very likely causing a pandemic. Since the novel coronavirus has been reported to be capable of endangering thousands of lives, it is extremely important to find out how the coronavirus is transmitted in human organs. Apart from fever and respiratory complications, gastrointestinal symptoms are observed in some patients with 2019-nCoV but the significance remains undetermined. The cell receptor angiotensin covering enzyme II (ACE2), which is the major receptor of SARS-nCoV, has been reported to be a cellular entry receptor of 2019-nCoV as well. Here, to more precisely explore the potential pathogen transmission route of the 2019-nCoV infections in the gastrointestinal tract, we analyzed the ACE2 RNA expression profile in the colon tissue of healthy adults and colorectal cancer patients of our cohort and other databases. The data indicates that ACE2 is mainly expressed in epithelial cells of the colon. The expression of ACE2 is gradually increased from healthy control, adenoma to colorectal cancer patients in our cohort as well as in the external Asian datasets. According to the expression profile of ACE2 in colon epithelial cells, we speculate adenoma and colorectal cancer patients are more likely to be infected with 2019-nCoV than healthy people. Our data may provide a theoretical basis for the classification and management of future 2019-nCoV susceptibility people in clinical application.</jats:p>",2020-02-23,"['Haoyan Chen', 'Baoqin Xuan', 'Yuqing Yan', 'Xiaoqiang Zhu', 'Chaoqin Shen', 'Gang Zhao', 'Linhua Ji', 'Danhua Xu', 'Hua Xiong', 'TaChung Yu', 'Xiaobo Li', 'Qiang Liu', 'Yingxuan Chen', 'Yun Cui', 'Jie Hong', 'Jing-Yuan Fang']",,,,True
f9c6a656d0ce352cc1fa0df8d83e6d4a1f53d7c2,medrxiv,Estimating the Case Fatality Risk of COVID-19 using Cases from Outside China,doi.org/10.1101/2020.02.15.20023499,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>There is large uncertainty around the case fatality risk (CFR) for COVID-19 in China. Therefore, we considered symptomatic cases outside of China (countries/settings with 20+ cases) and the proportion who are in intensive care units (4.0%, 14/349 on 13 February 2020). Given what is known about CFRs for ICU patients with severe respiratory conditions from a meta-analysis, we estimated a CFR of 1.37% (95%CI: 0.57% to 3.22%) for COVID-19 cases outside of China.</jats:p>",2020-02-18,"['Nick Wilson', 'Amanda Kvalsvig', 'Lucy Telfar Barnard', 'Michael Baker']",,,,True
10138816c67a562b55bc9c2b882b62c81fc4b062,medrxiv,Epidemic analysis of COVID-19 in China by dynamical modeling,doi.org/10.1101/2020.02.16.20023465,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The outbreak of the novel coronavirus (2019-nCoV) epidemic has attracted world- wide attention. Herein, we propose a mathematical model to analyzes this epidemic, based on a dynamic mechanism that incorporating the intrinsic impact of hidden la- tent and infectious cases on the entire process of transmission. Meanwhile, this model is validated by data correlation analysis, predicting the recent public data, and back- tracking, as well as sensitivity analysis. The dynamical model reveals the impact of various measures on the key parameters of the epidemic. According to the public data of NHCs from 01/20 to 02/09, we predict the epidemic peak and possible end time for 5 different regions. The epidemic in Beijing and Shanghai, Mainland/Hubei and Hubei/Wuhan, are expected to end before the end of February, and before mid- March respectively. The model indicates that, the outbreak in Wuhan is predicted to be ended in the early April. As a result, more effective policies and more efforts on clinical research are demanded. Moreover, through the backtracking simulation, we infer that the outbreak of the epidemic in Mainland/Hubei, Hubei/Wuhan, and Wuhan can be dated back to the end of December 2019 or the beginning of January 2020.</jats:p>",2020-02-18,"['Liangrong Peng', 'Wuyue Yang', 'Dongyan Zhang', 'Changjing Zhuge', 'Liu Hong']",,,,True
b117016a887f05386acc4387dab5bf8c769cf90e,medrxiv,Simulating and Forecasting the Cumulative Confirmed Cases of SARS-CoV-2 in China by Boltzmann Function-based Regression Analyses,doi.org/10.1101/2020.02.16.20023564,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>An ongoing outbreak of atypical pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2) is hitting Wuhan City and has spread to other provinces/cities of China and overseas. It very urgent to forecast the future course of the outbreak. Here, we provide an estimate of the potential total number of confirmed cases in mainland China by applying Boltzmann-function based regression analyses. We found that the cumulative number of confirmed cases from Jan 21 to Feb 14, 2020 for mainland China, Hubei Province, Wuhan City and other provinces were all well fitted with the Boltzmann function (R2 being close to 0.999). The potential total number of confirmed cases in the above geographic regions were estimated at 95% confidence interval (CI) as 79589 (71576, 93855), 64817 (58223, 77895), 46562 (40812, 57678) and 13956 (12748, 16092), respectively. Notably, our results suggest that the number of daily new confirmed cases of SARS-CoV-2 in mainland China (including Hubei Province) will become minimal between Feb 28 and Mar 10, 2020, with 95% CI. In addition, we found that the data of cumulative confirmed cases of 2003 SARS-CoV in China and Worldwide were also well fitted to the Boltzmann function. To our knowledge this is the first study revealing that the Boltzmann function is suitable to simulate epidemics. The estimated potential total number of confirmed cases and key dates for the SARS-CoV-2 outbreak may provide certain guidance for governments, organizations and citizens to optimize preparedness and response efforts.</jats:p>",2020-02-18,"['Xinmiao Fu', 'Qi Ying', 'Tieyong Zeng', 'Tao Long', 'Yan Wang']",,,,True
8bd8158e4a47c65b12a462b49b4b8b4af1488dc3,medrxiv,Estimation of the final size of the coronavirus epidemic by the logistic model,doi.org/10.1101/2020.02.16.20023606,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>In the note, the logistic growth regression model is used for the estimation of the final size and its peak time of the coronavirus epidemic. Based on available data estimation the final size will be about 90 000 cases and the peak time was on 10 Feb 2020.</jats:p>",2020-02-18,['milan batista'],,,,True
d069dfb7f0aefcdc2c890a1bbe773ebd26b01a55,medrxiv,Utilize State Transition Matrix Model to Predict the Novel Corona Virus Infection Peak and Patient Distribution,doi.org/10.1101/2020.02.16.20023614,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Since December 2019, a pneumonia caused by the 2019 novel coronavirus (2019-nCoV) has broken out in Wuhan, Hubei province, China. The continuous rising of infected cases has imposed overwhelming pressure on public health decision and medical resource allocation in China. We managed to forecast the infection peak time in Hubei province and the severe and critical case distribution. Methods: We used data resource according to cases reported by the National Health Commission of the People's Republic of China (Jan 25, 2019, to Feb 28, 2020) as the training set to deduce the arrival of the peak infection time and the number of severe and critical cases in Wuhan on subsequent days. Medical observation, discharge, infected, non-Severe, infected and severe, cure and death data were collected and analyzed. Using this state transition matrix model, we will be able predict when the inflection peak time (the maximum open infection cases) in Hubei Province will occur. Also, we can use this model to predict the patient distribution (severe, non-severe) to better allocate medical resource. Under relative pessimistic scenario, the inflection peak time is April 6-April 14. The numbers of critically ill and critically ill patients will lie between 8300-9800 and 2200-2700, respectively.  Results: In very optimistic scenarios (daily NCC decay rate of -10%), the peak time of open inflection cases will arrive around February 23-February 26. At the same time, there will be a peak in the numbers of severely ill and critically ill patients, between 6800-7200 and 1800-2000, respectively. In a relative optimistic scenario (daily NCC decay rate of -5%), the inflection case peak time will arrive around February 28-March 2. The numbers of critically ill and critically ill patients will lie between 7100-7800 and 1900-2200, respectively. In a relatively pessimistic scenario (daily NCC decay rate of -1%), the inflection peak time does not arrive around the end of March. Estimated time is April 6-April 14. The numbers of critically ill and critically ill patients will lie between 8300-9800 and 2200-2700, respectively. We are using the diagnosis rate, mortality rate, cure rate as the 2/8 data. There should be room for improvement, if these metrics continue to improve. In that case, the peak time will arrive earlier than our estimation. Also, the severe and critical case ratios are likely to decline as the virus becomes less toxic and medical conditions improve. If that happens, the peak numbers will be lower than predicted above.  Conclusion: We can infer that we are still not close to the end of this outbreak and the number of critically ill patients is still climbing. Assisting critical care resources in Hubei province requires the government to consider further tilt, and it is vital to make reasonable management of doctors and medical assistance systems to curb the transmission trend.</jats:p>",2020-02-19,"['Ke Wu', 'Junhua Zheng', 'Jian Chen']",,,,True
3da1a03cb675f463b0d8e30744aa33512241dd29,medrxiv,SEIR Transmission dynamics model of 2019 nCoV coronavirus with considering the weak infectious ability and changes in latency duration,doi.org/10.1101/2020.02.16.20023655,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Pneumonia patients of 2019-ncov in latent period are not easy to be effectively quarantined, but there is evidence that they have strong infectious ability. Here, the infectious ability of patients during the latent period is slightly less than that of the infected patients was assumed. We established a new SEIR propagation dynamics model, that considered the weak transmission ability of the incubation period, the variation of the incubation period length, and the government intervention measures to track and isolate comprehensively. Based on the raw epidemic data of China from January 23, 2020 to February 10, 2020, the dynamic parameters of the new present SEIR model are fitted. Through the Euler integration algorithm to solve the model, the effect of infectious ability of incubation patients on the theoretical estimation of the present SEIR model was analyzed, and the occurrence time of peak number in China was predicted.</jats:p>",2020-02-20,"['Pengpeng Shi', 'Shengli Cao', 'Peihua Feng']",,,,True
7325363d061f0f4699e29bfa544438e14e7c207d,medrxiv,Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients,doi.org/10.1101/2020.02.16.20023671,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: The dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear.  Method: Peripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays.   Findings: Of the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts but increases in neutrophil counts than 27 mild cases. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8 + T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-γ levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-CD8+ T cell ratio (N8R) were identified as the most powerful prognostic factor affecting the prognosis for severe COVID-19.  Conclusion: The degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R may serve as a useful prognostic factor for early identification of severe COVID-19 cases.</jats:p>",2020-02-18,"['Jing Liu', 'Sumeng Li', 'Jia Liu', 'Boyun Liang', 'Xiaobei Wang', 'Hua Wang', 'Wei Li', 'Qiaoxia Tong', 'Jianhua Yi', 'Lei Zhao', 'Lijuan Xiong', 'Chunxia Guo', 'Jin Tian', 'Jinzhuo Luo', 'Jinghong Yao', 'Ran Pang', 'Hui Shen', 'Cheng Peng', 'Ting Liu', 'Qian Zhang', 'Jun Wu', 'Ling Xu', 'Sihong Lu', 'Baoju Wang', 'Zhihong Weng', 'Chunrong Han', 'Huabing Zhu', 'Ruxia Zhou', 'Helong Zhou', 'Xiliu Chen', 'Pian Ye', 'Bin Zhu', 'Shengsong He', 'Yongwen He', 'Shenghua Jie', 'Ping Wei', 'Jianao Zhang', 'Yinping Lu', 'Weixian Wang', 'Li Zhang', 'Ling Li', 'Fengqin Zhou', 'Jun Wang', 'Ulf Dittmer', 'Mengji Lu', 'Yu Hu', 'Dongliang Yang', 'Xin Zheng']",,,,True
6445688d3f59cb7e02f2a8b28450cdf118a8a373,medrxiv,Contacts in context: large-scale setting-specific social mixing matrices from the BBC Pandemic project,doi.org/10.1101/2020.02.16.20023754,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Social mixing patterns are crucial in driving transmission of infectious diseases and informing public health interventions to contain their spread. Age-specific social mixing is often inferred from surveys of self-recorded contacts which by design often have a very limited number of participants. In addition, such surveys are rare, so public health interventions are often evaluated by considering only one such study. Here we report detailed population contact patterns for United Kingdom based self-reported contact data from over 36,000 volunteers that participated in the massive citizen science project BBC Pandemic. The amount of data collected allows us generate fine-scale age-specific population contact matrices by context (home, work, school, other) and type (conversational or physical) of contact that took place. These matrices are highly relevant for informing prevention and control of new outbreaks, and evaluating strategies that reduce the amount of mixing in the population (such as school closures, social distancing, or working from home). In addition, they finally provide the possibility to use multiple sources of social mixing data to evaluate the uncertainty that stems from social mixing when designing public health interventions.</jats:p>",2020-02-19,"['Petra Klepac', 'Adam J Kucharski', 'Andrew JK Conlan', 'Stephen Kissler', 'Maria Tang', 'Hannah Fry', 'Julia R Gog']",,,,True
d1ac7f1c8343a9635b2cefe9b70eae4e03138b60,medrxiv,Study on SARS-COV-2 transmission and the effects of control measures in China,doi.org/10.1101/2020.02.16.20023770,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective To reconstruct the transmission trajectory of SARS-COV-2 and analyze the effects of control measures in China. Methods Python 3.7.1 was used to write a SEIR class to model the epidemic procedure and a back propagation class to estimate the initial true infected number. The epidemic area in China was divided into three parts, Wuhan city, Hubei province (except Wuhan) and China (except Hubei) based on the different transmission pattern. A limitation factor for the medical resource was imposed to model the infected but not quarantined. Credible data source from Baidu Qianxi were used to assess the number of infected cases migrated from Wuhan to other areas. Results Basic reproduction number, R0, was 3.6 in the very early stage. The true infected number was 4508 in our model in Wuhan before January 22, 2020. By January 22 2020, it was estimated that 1764 infected cases migrated from Wuhan to other cities in Hubei province. Effective reproductive number, R, gradually decreased from 3.6 (Wuhan, stage 1), 3.4 (Hubei except Wuhan, stage 1) and 3.3 (China except Hubei, stage 1) to 0.67 (Wuhan, stage 4), 0.83 (Hubei except Wuhan, stage 2) and 0.63 (China except Hubei, stage 2), respectively. Especially after January 23, 2020 when Wuhan City was closed, the infected number showed a turning point in Wuhan. By early April, there would be 42073, 21342 and 13384 infected cases in Wuhan, Hubei (except Wuhan) and China (except Hubei) respectively, and there would be 2179, 633 and 107 death in Wuhan, Hubei (except Wuhan) and China (except Hubei) respectively. Conclusion A series of control measures in China have effectively prevented the spread of COVID-19, and the epidemic will end in early April.</jats:p>",2020-02-18,"['Bo Zhang', 'Hongwei Zhou', 'Fang Zhou']",,,,False
e62e453735dc2022f4d81aa9b22769de30d0bb90,medrxiv,When will the battle against novel coronavirus end in Wuhan: a SEIR modeling analysis,doi.org/10.1101/2020.02.16.20023804,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Recent outbreak of 2019-nCoV in Wuhan raised serious public health concerns. By February 15, 2020 in Wuhan, the total number of confirmed infection cases has reached 37,914, and the number of deaths has reached 1123, accounting for 56.9% of the total confirmed cases and 73.7% of the total deaths in China. People are eager to know when the epidemic will be completely controlled and when people's work and life will be on the right track. In this study we analyzed the epidemic dynamics and trend of 2019-nCoV in Wuhan by using the data after the closure of Wuhan city till February 12, 2020 based on the SEIR modeling method. The optimal parameters were estimated as R0=1.44 (interquartile range: 1.40-1.47)，TI=14 (interquartile range: 14-14) and TE=3.0 (interquartile range: 2.8-3.1). Based on these parameters, the number of infected individuals in Wuhan city may reach the peak around February 19 at about 45,000 people. Once entering March, the epidemic would gradually decline, and end around the late March. It is worth noting that the above prediction is based on the assumption that the number of susceptible population N = 200,000 will not increase. If the epidemic situation is not properly controlled, the peak of infected number can be further increased and the peak time will be a little postponed. It was expected that the epidemic would subside in early March, and disappear gradually towards the late March.</jats:p>",2020-02-18,"['lianglu zhang', 'kangkang wan', 'jing chen', 'changming lu', 'lanlan dong', 'zhicheng wu']",,,,True
33bd85ea9ca61c4d0674c43ae5b901b271b46f1e,medrxiv,Fractal kinetics of COVID-19 pandemic,doi.org/10.1101/2020.02.16.20023820,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>We give an update to the original paper posted on 2/17/20 -- now (as of 3/1/20) the China deaths are rapidly decreasing, and we find an exponential decline to the power law similar to the that predicted by the network model of  \citet{vazquez_polynomial_2006}.  At the same time, we see non-China deaths increasing rapidly, and similar to the early behavior of the China statistics.  Thus, we see three stages of the spread of the disease in terms of number of deaths: exponential growth, power-law behavior, and then exponential decline in the daily rate.          (Original abstract) The novel coronavirus (COVID-19) continues to grow rapidly in China and is spreading in other parts of the world. The classic epidemiological approach in studying this growth is to quantify a reproduction number and infection time, and this is the approach followed by many studies on the epidemiology of this disease.  However, this assumption leads to exponential growth, and while the growth rate is high, it is not following exponential behavior. One approach that is being used is to simply keep adjusting the reproduction number to match the dynamics. Other approaches use rate equations such as the SEIR and logistical models.  Here we show that the current growth closely follows power-law kinetics, indicative of an underlying fractal or small-world network of connections between susceptible and infected individuals. Positive deviations from this growth law might indicate either a failure of the current containment efforts while negative deviations might indicate the beginnings of the end of the pandemic.  We cannot predict the ultimate extent of the pandemic but can get an estimate of the growth of the disease.</jats:p>",2020-02-20,"['Anna L. Ziff', 'Robert M. Ziff']",,,,True
fbebe4b66073c44cface2e842754bce26e3e2913,medrxiv,Risk map of the novel coronavirus (2019-nCoV) in China: proportionate control is needed,doi.org/10.1101/2020.02.16.20023838,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background China is running a national level antivirus campaign against the novel coronavirus (2019-nCoV). Strict control measures are being enforced in either the populated areas and remote regions. While the virus is closed to be under control, tremendous economic loss has been caused. Methods and findings We assessed the pandemic risk of 2019-nCoV for all cities/regions in China using the random forest algorithm, taking into account the effect of five factors: the accumulative and increased numbers of confirmed cases, total population, population density, and GDP. We defined four levels of the risk, corresponding to the four response levels to public health emergencies in China. The classification system has good consistency among cities in China, as the error rate of the confusion matrix is 1.58%. Conclusions The pandemic risk of 2019-nCoV is dramatically different among the 442 cities/regions. We recommend to adopt proportionate control policy according to the risk level to reduce unnecessary economic loss.</jats:p>",2020-02-18,"['Xinhai Li', 'Xumao Zhao', 'Yingqiang Lou', 'Yuehua Sun']",,,,True
d4cfb1fc4fc53abbc1d4b0ca60276c6af6632c3c,medrxiv,Clinical and immunologic features in severe and moderate forms of Coronavirus Disease 2019,doi.org/10.1101/2020.02.16.20023903,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background Since late December, 2019, an outbreak of pneumonia cases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and continued to spread throughout China and across the globe. To date, few data on immunologic features of Coronavirus Disease 2019 (COVID-19) have been reported. Methods In this single-centre retrospective study, a total of 21 patients with pneumonia who were laboratory-confirmed to be infected with SARS-CoV-2 in Wuhan Tongji hospital were included from Dec 19, 2019 to Jan 27, 2020. The immunologic characteristics as well as their clinical, laboratory, radiological features were compared between 11 severe cases and 10 moderate cases. Results Of the 21 patients with COVID-19, only 4 (19%) had a history of exposure to the Huanan seafood market. 7 (33.3%) patients had underlying conditions. The average age of severe and moderate cases was 63.9 and 51.4 years, 10 (90.9%) severe cases and 7 (70.0%) moderate cases were male. Common clinical manifestations including fever (100%, 100%), cough (70%, 90%), fatigue (100%, 70%) and myalgia (50%, 30%) in severe cases and moderate cases. PaO2/FiO2 ratio was significantly lower in severe cases (122.9) than moderate cases (366.2). Lymphocyte counts were significantly lower in severe cases (7000 million/L) than moderate cases (11000 million/L). Alanine aminotransferase, lactate dehydrogenase levels, high-sensitivity C-reactive protein and ferritin were significantly higher in severe cases (41.4 U/L, 567.2 U/L, 135.2 mg/L and 1734.4 ug/L) than moderate cases (17.6 U/L, 234.4 U/L, 51.4 mg/L and 880.2 ug /L). IL-2R, TNF-α and IL-10 concentrations on admission were significantly higher in severe cases (1202.4 pg/mL, 10.9 pg/mL and 10.9 pg/mL) than moderate cases (441.7 pg/mL, 7.5 pg/mL and 6.6 pg/mL). Absolute number of total T lymphocytes, CD4+T cells and CD8+T cells decreased in nearly all the patients, and were significantly lower in severe cases (332.5, 185.6 and 124.3 million/L) than moderate cases (676.5, 359.2 and 272.0 million/L). The expressions of IFN-γ by CD4+T cells tended to be lower in severe cases (14.6%) than moderate cases (23.6%). Conclusion The SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+T cells, resulting in significant decrease in number as well as IFN-γ production, which may be associated with disease severity. Together with clinical characteristics, early immunologic indicators including diminished T lymphocytes and elevated cytokines may serve as potential markers for prognosis in COVID-19.</jats:p>",2020-02-19,"['Guang Chen', 'Di Wu', 'Wei Guo', 'Yong Cao', 'Da Huang', 'Hongwu Wang', 'Tao Wang', 'Xiaoyun Zhang', 'Huilong Chen', 'Haijing Yu', 'Xiaoping Zhang', 'Minxia Zhang', 'Shiji Wu', 'Jianxin Song', 'Tao Chen', 'Meifang Han', 'Shusheng Li', 'Xiaoping Luo', 'Jianping Zhao', 'Qin Ning']",,,,True
87e2e48081308341e24ea8bcc1f52297e16697c6,medrxiv,Estimating the case fatality ratio of the COVID-19 epidemic in China,doi.org/10.1101/2020.02.17.20023630,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Corona Virus Disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan city and rapidly spread throughout China since late December 2019. Crude case fatality ratio (CFR) with dividing the number of known deaths by the number of confirmed cases does not represent the true CFR and might be off by orders of magnitude. We aim to provide a precise estimate of the CFR of COVID-19 using statistical models at the early stage of the epidemic. Methods: We extracted data from the daily released epidemic report published by the National Health Commission P. R. China from 20 Jan 2020, to 1 March 2020. Competing risk model was used to obtain the cumulative hazards for death, cure, and cure-death hazard ratio. Then the CFR was estimated based on the slope of the last piece in joinpoint regression model, which reflected the most recent trend of the epidemic.  Results: As of 1 March 2020, totally 80,369 cases were diagnosed as COVID-19 in China. The CFR of COVID-19 were estimated to be 70.9% (95% CI: 66.8%-75.6%) during Jan 20-Feb 2, 20.2% (18.6%-22.1%) during Feb 3-14, 6.9% (6.4%-7.4%) during Feb 15-23, 1.5% (1.4%-1.6%) during Feb 24-March 1 in Hubei province, and 20.3% (17.0%-25.3%) during Jan 20-28, 1.9% (1.8%-2.1%) during Jan 29-Feb 12, 0.9% (0.8%-1.1%) during Feb 13-18, 0.4% (0.4%-0.5%) during Feb 19-March 1 in other areas of China, respectively.  Conclusions: Based on analyses of public data, we found that the CFR in Hubei was much higher than that of other regions in China, over 3 times in all estimation. The CFR would follow a downwards trend based on our estimation from recently released data. Nevertheless, at early stage of outbreak, CFR estimates should be viewed cautiously because of limited data source on true onset and recovery time.</jats:p>",2020-02-20,"['Xing Wang', 'Zihui Ma', 'Yi Ning', 'Chen Chen', 'Rujin Chen', 'Qiwen Chen', 'Heng Zhang', 'Chunming Li', 'Yan He', 'Tao Wang', 'Cheng Tong', 'Junqing Wu', 'Yuyan Li', 'Handong Ma', 'Shaodian Zhang', 'Hongxin Zhao']",,,,False
fe685aa676e739bd52ba2585a7e5b27c55e2d0d6,medrxiv,Evidence for gastrointestinal infection of SARS-CoV-2,doi.org/10.1101/2020.02.17.20023721,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The new coronavirus (SARS-CoV-2) outbreak originating from Wuhan, China, poses a threat to global health. While it's evident that the virus invades respiratory tract and transmits from human to human through airway, other viral tropisms and transmission routes remain unknown. We tested viral RNA in stool from 73 SARS-CoV-2-infected hospitalized patients using rRT-PCR. 53.42% of the patients tested positive in stool. 23.29% of the patients remained positive in feces even after the viral RNA decreased to undetectable level in respiratory tract. The viral RNA was also detected in gastrointestinal tissues. Furthermore, gastric, duodenal and rectal epithelia showed positive immunofluorescent staining of viral host receptor ACE2 and viral nucleocapsid protein in a case of SARS-CoV-2 infection. Our results provide evidence for gastrointestinal infection of SARS-CoV-2, highlighting its potential fecal-oral transmission route.</jats:p>",2020-02-20,"['Fei Xiao', 'Meiwen Tang', 'Xiaobin Zheng', 'Chunna Li', 'Jianzhong He', 'Zhongsi Hong', 'Siwen Huang', 'Zhenyi Zhang', 'Xianqi Lin', 'Zhaoxiong Fang', 'Renxu Lai', 'Shoudeng Chen', 'Jing Liu', 'Jin Huang', 'Jinyu Xia', 'Zhonghe Li', 'Guanmin Jiang', 'Ye Liu', 'Xiaofeng Li', 'Hong Shan']",,,,True
0cad40f50e41144e8b64744251515eca8cfac5f7,medrxiv,The reproductive number R0 of COVID-19 based on estimate of a statistical time delay dynamical system,doi.org/10.1101/2020.02.17.20023747,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>In this paper, we estimate the reproductive number <jats:italic>R</jats:italic><jats:sub>0</jats:sub> of COVID-19 based on Wallinga and Lipsitch framework {11} and a novel statistical time delay dynamic system. We use the observed data reported in CCDC's paper to estimate distribution of the generation interval of the infection and apply  the simulation results from the time delay dynamic system as well as released data from CCDC  to fit the growth rate. The conclusion is: Based our Fudan-CCDC model, the growth rate <jats:italic>r</jats:italic> of COVID-19 is almost in [0.30, 0.32] which is  larger than  the growth rate 0.1  estimated by CCDC {9},   and the  reproductive number <jats:italic>R</jats:italic><jats:sub>0</jats:sub> of COVID-19 is estimated by 3.25≤ <jats:italic>R</jats:italic><jats:sub>0</jats:sub> ≤3.4 if we simply use <jats:italic>R</jats:italic>=1+<jats:italic>r</jats:italic>*<jats:italic>T</jats:italic><jats:sub>c</jats:sub> with <jats:italic>T</jats:italic><jats:sub>c</jats:sub>=7.5, which is bigger than that of SARS. Some evolutions and predictions are listed.</jats:p>",2020-02-20,"['Nian Shao', 'Jin Cheng', 'Wenbin Chen']",,,,True
891bbc26d5c655131ba93482ca61238fc6f3d5f7,medrxiv,"COVID-19 in a Designated Infectious Diseases HospitalOutside Hubei Province,China",doi.org/10.1101/2020.02.17.20024018,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background A new type of novel coronavirus infection (COVID-19) occurred in Wuhan, Hubei Province. Previous investigations reported patients in Wuhan city often progressed into severe or critical and had a high mortality rate.The clinical characteristics of affected patients outside the epicenter of Hubei province are less well understood. Methods All confirmed COVID-19 case treated in the Third People's Hospital of Shenzhen,from January 11, 2020 to February 6, 2020, were included in this study. We analyzed the epidemiological and clinical features of these cases to better inform patient management in normal hospital settings.  Results Among the 298 confirmed cases, 233(81.5%) had been to Hubei while 42(14%) had not clear epidemiological history. Only 192(64%) cases presented with fever as initial symptom. The lymphocyte count decreased in 38% patients after admission. The number (percent) of cases classified as non-severe and severe was 240(80.6%) and 58(19.4%) respectively. Thirty-two patients (10.7%) needed ICU care. Compared to the non-severe cases, severe cases were associated with older age, underlying diseases, as well as higher levels of CRP, IL-6 and ESR. The median (IRQ) duration of positive viral test were 14(10-19). Slower clearance of virus was associated with higher risk of progression to severe clinical condition. As of February 14, 2020, 66(22.1%) patients were discharged and the overall mortality rate remains 0. Conclusions In a designated hospital outside the Hubei Province, COVID-19 patients were mainly characterized by mild symptoms and could be effectively manage by properly using the existing hospital system.</jats:p>",2020-02-19,"['Qingxian Cai', 'Deliang Huang', 'Pengcheng Ou', 'Hong Yu', 'Zhibin Zhu', 'Zhang Xia', 'Yinan Su', 'Zhenghua Ma', 'Yiming Zhang', 'Zhiwei Li', 'Qing He', 'Yang Fu', 'Lei Liu', 'Jun Chen']",,,,False
dac1b1607ae72b9509ab26367e0d55016e8132a8,medrxiv,Epidemic Situation of Novel Coronavirus Pneumonia in China mainland,doi.org/10.1101/2020.02.17.20024034,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>[Objective] Analyze the occurrence of novel coronavirus pneumonia(NCP) in China mainland, explore the epidemiological rules, and evaluate the effect of prevention and control. [Methods] From December 1, 2019 to February 14, 2020, Analysis of 66,492 confirmed cases of NCP in China mainland. [Results] From December 1, 2019 to February 14, 2020, a total of 66,492 cases of NCP were confirmed in China mainland, a total of 54,406 cases were confirmed in Hubei Province, a total of 37,914 cases were confirmed in Wuhan city. On February 5, 2020, the number of suspected cases of NCP in China mainland reached a maximum of 5,328. Since then, the suspected cases have shown a significant downward trend. On February 4, 2020, the number of confirmed cases has gradually decreased in China mainland since then. On February 12, 2020, the number of confirmed cases of NCP in China mainland increased explosively to 15,152, and then began to decline. From February 3, 2020, except for Hubei Province, In China mainland, the number of newly confirmed cases of NCP has continued to decline; From December 1, 2019 to February 14, 2020, a total of 1,523 cases of NCP deaths in China mainland, a cumulative cure of 8096 cases, and  mortality and cure rate were 2.29% (1523/66492) and 12.18% (8096/66492) respectively; Starting from January 27, 2020, The spread index of NCP gradually declined, and the extinction index of NCP rose  little by little from January 29, 2020. [Conclusion] Starting from February 5, 2020, the number of suspected cases of the NCP is gradually decrease in China mainland. From February 3, 2020, the number of newly confirmed cases of NCP is continuous decline in China mainland except Hubei Province, This shows that the control of the transmission of NCP has achieved. Judged from the number of confirmed cases of NCP, controlling the outbreak in China mainland is to control the epidemic in Hubei province, and the key to controlling the outbreak in Hubei province is to control the epidemic in Wuhan city; Judging from the gradual increase in the number and cure rate of the NCP, and the gradual decline in the number of deaths and mortality, the trend of outbreak control and treatment is getting better; A decrease of the NCP spread index indicates a slowdown in the spread of the virus, but the cumulative confirmed cases is still increase, so the epidemic will continue for some time. However, the turning point of the epidemic in mainland China has not yet occurred. On February 12, 2020, the turning point of the epidemic in China mainland except Hubei province, has turned up.</jats:p>",2020-02-18,"['Liu youbin', 'Li bao hong']",,,,True
541e7d329fa466fe7b961263666386dddec75894,medrxiv,A quantitative framework to define the end of an outbreak: application to Ebola Virus Disease,doi.org/10.1101/2020.02.17.20024042,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Declaring the end of an outbreak is an important step in controlling infectious disease outbreaks. An objective estimation of the probability of cases arising in the future is important to reduce the risk of post-declaration flare-ups. We developed a simulation-based model to quantify that probability. We tested it on simulated Ebola Virus Disease (EVD) data and found this probability was most sensitive to the instantaneous reproduction number, the reporting rate, and the delay between symptom onset and recovery or death of the last detected case. For EVD, our results suggest that the current WHO criterion of 42 days since the outcome of the last detected case is too short and very sensitive to underreporting. The 90 days of enhanced surveillance period after the end-of-outbreak declaration is therefore crucial to capture potential flare-ups of cases. Hence, we suggest a shift to a preliminary end-of-outbreak declaration after 63 days from the symptom onset day of the last detected case. This should be followed by a 90-day enhanced surveillance, after which the official end-of-outbreak can be declared. This corresponds to less than 5% probability of flare ups in most of the scenarios examined. Our quantitative framework could be adapted to define end-of-outbreak criteria for other infectious diseases.</jats:p>",2020-02-20,"['Bimandra A Djaafara', 'Natsuko Imai', 'Esther Hamblion', 'Benido Impouma', 'Christl A Donnelly', 'Anne Cori']",,,,True
a6d2875c8b70a41ea815511417546a0689816964,medrxiv,"Estimating number of global importations of COVID-19 from Wuhan, risk of transmission outside mainland China and COVID-19 introduction index between countries outside mainland China",doi.org/10.1101/2020.02.17.20024075,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background The emergence of a novel coronavirus (SARS-CoV-2) in Wuhan, China in early December 2019 has caused widespread transmission within the country, with over 1,000 deaths reported to date. Other countries have since reported coronavirus disease 2019 (COVID-19) importation from China, with some experiencing local transmission and even case importation from countries outside China. We aim to estimate the number of cases imported from Wuhan to each country or territory outside mainland China, and with these estimates assess the risk of onward local transmission and the relative potential of case importation between countries outside China.  Methods We used the reported number of cases imported from Wuhan and flight data to generate an uncertainty distribution for the estimated number of imported cases from Wuhan to each location outside mainland China. This uncertainty was propagated to quantify the local outbreak risk using a branching process model. A COVID-19 introduction index was derived for each pair of donor and recipient countries, accounting for the local outbreak risk in the donor country and the between-country connectivity.  Results We identified 13 countries or territories outside mainland China that may have under-detected COVID-19 importation from Wuhan, such as Thailand and Indonesia. In addition, 16 countries had a local outbreak risk estimate exceeding 50%, including four outside Asia. The COVID-19 introduction index highlights potential locations outside mainland China from which cases may be imported to each recipient country.  Conclusions As SARS-CoV-2 continues to spread globally, more epicentres may emerge outside China. Hence, it is important for countries to remain alert for the possibilities of viral introduction from other countries outside China, even before local transmission in a source country becomes known.</jats:p>",2020-02-20,"['Haoyang Sun', 'Borame Lee Dickens', 'Mark Chen', 'Alex Richard Cook', 'Hannah Eleanor Clapham']",,,,True
f0e75c4697317cbd0e3a5cdd722fe0526595db64,medrxiv,Clinical features and progression of acute respiratory distress syndrome in coronavirus disease 2019,doi.org/10.1101/2020.02.17.20024166,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a cluster of coronavirus disease 2019 (COVID-19). We reported the clinical characteristics of COVID-19 patients with acute respiratory distress syndrome (ARDS), and further investigated the treatment and progression of ARDS in COVID-19. Methods: This study enrolled 109 patients with COVID-19 admitted to the Central Hospital of Wuhan, a designated hospital in Wuhan, China, from January 2 to February 1, 2020. Patients were followed up to February 12, 2020. The clinical data were collected from the electronic medical records. The differences in the treatment and progression with the time and the severity of ARDS were determined. Findings: Among 109 patients, mean age was 55 years, and 59 patients were male. With a median 15 days (range, 4 to 30 days) follow-up period, 31 patients (28.4%) died, while 78 (71.6%) survived and discharged. Of all patients, 53 (48.6%) developed ARDS. Compared to non-ARDS patients, ARDS patients were elder (mean age, 61 years vs. 49 years), and more likely to have the coexistent conditions, including diabetes (20.8% vs. 1.8%), cerebrovascular disease (11.3% vs. 0%), and chronic kidney disease (15.1% vs. 3.6%). Compared to mild ARDS patients, those with moderate and severe ARDS had higher mortality rates. No significant effect of antivirus, glucocorticoid, or immunoglobulin treatment on survival was observed in patients with ARDS. Interpretation: The mortality rate increased with the severity of ARDS in COVID-19, and the effects of current therapies on the survival for these patients were not satisfactory, which needs more attention from clinicians.  Funding: Health and Family Planning Commission of Wuhan Municipality.</jats:p>",2020-02-20,"['Yanli Liu', 'Wenwu Sun', 'Jia Li', 'Liangkai Chen', 'Yujun Wang', 'Lijuan Zhang', 'Li Yu']",,,,True
341fe593ea84b66223d50924bddbba252c37bc4e,medrxiv,Tracking and Predicting COVID-19 Epidemic in China Mainland,doi.org/10.1101/2020.02.17.20024257,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>By proposing a varying coefficient Susceptible-Infected-Removal model (vSIR), we track the epidemic of COVID-19 in 30 provinces in China and 15 cities in Hubei province, the epicenter of the outbreak. It is found that the spread of COVID-19 has been significantly slowing down within the two weeks from January 27 to February 10th with 87.0% and 84.3% reductions in the reproduction number R0 among the 30 provinces and 15 Hubei cities, respectively. This suggests the extreme control measures implemented since January 23, which include cutting off Wuhan and many other cities and towns, a great public awareness and high level of self isolation at home, have contributed to a substantial decline in the reproductivity of the COVID-19 in China. We predict that Hubei province will reach its peak between February 20 and 22, 2020, and if the removal rate can be increased to 0.1, the epidemic outside Hubei province will end in May 2020, and inside Hubei in early June.</jats:p>",2020-02-20,"['Haoxuan Sun', 'Yumou Qiu', 'Han Yan', 'Yaxuan Huang', 'Yuru Zhu', 'Song Xi Chen']",,,,True
6186828135d9e5e7e50f66567505d02e910b3ee2,medrxiv,Association between 2019-nCoV transmission and N95 respirator use,doi.org/10.1101/2020.02.18.20021881,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>2019-nCoV had caused pneumonia outbreak in Wuhan. Existing evidence have confirmed the human-to-human transmission of 2019-nCoV. We retrospectively collected infection data from 2 January to 22 January at six departments from Zhongnan Hospital of Wuhan University. In our study, we found N95 respirators, disinfection and hand washing can help to reduce the risk of 2019-nCoV infection in medical staffs. Our results call for re-emphasizing strict occupational protection code in battling this novel contagious disease. The risk of 2019-nCoV infection was higher in the open area than in the quarantined area. N95 may be more effective for 2019-nCoV infections.</jats:p>",2020-02-19,"['Xinghuan Wang', 'Zhenyu Pan', 'Zhenshun Cheng']",,,,True
db142fe07544dcf0e454f8a9f39452f0aa92a6ca,medrxiv,Kidney impairment is associated with in-hospital death of COVID-19 patients,doi.org/10.1101/2020.02.18.20023242,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Information on kidney impairment in patients with coronavirus disease 2019 (COVID-19) is limited. This study aims to assess the prevalence and impact of abnormal urine analysis and kidney dysfunction in hospitalized COVID-19 patients in Wuhan. Method: We conducted a consecutive cohort study of COVID-19 patients admitted in a tertiary teaching hospital with 3 branches following a major outbreak in Wuhan in 2020. Hematuria, proteinuria, serum creatinine concentration and other clinical parameters were extracted from the electronic hospitalization databases and laboratory databases. Incidence rate for acute kidney injury (AKI) was examined during the study period. Association between kidney impairment and in-hospital death was analyzed. Results: We included 710 consecutive COVID19 patients, 89 (12.3%) of whom died in hospital. The median age of the patients was 63 years (inter quartile range, 51-71), including 374 men and 336 women. On admission, 44% of patients have proteinuria hematuria and 26.9% have hematuria, and the prevalence of elevated serum creatinine and blood urea nitrogen were 15.5% and 14.1% respectively. During the study period, AKI occurred in 3.2% patients. Kaplan-Meier analysis demonstrated that patients with kidney impairment have higher risk for in-hospital death. Cox proportional hazard regression confirmed that elevated serum creatinine, elevated urea nitrogen, AKI, proteinuria and hematuria was an independent risk factor for in-hospital death after adjusting for age, sex, disease severity, leukocyte count and lymphocyte count. Conclusion: The prevalence of kidney impairment (hematuria, proteinuria and kidney dysfunction) in hospitalized COVID-19 patients was high. After adjustment for confounders, kidney impairment indicators were associated with higher risk of in-hospital death. Clinicians should increase their awareness of kidney impairment in hospitalized COVID-19 patients.</jats:p>",2020-02-20,"['Yichun Cheng', 'Ran Luo', 'Kun Wang', 'Meng Zhang', 'Zhixiang Wang', 'Lei Dong', 'Junhua Li', 'Ying Yao', 'Shuwang Ge', 'Gang Xu']",,,,True
b9548530d954b407b35fb266e2b4192402c982a1,medrxiv,"Phase adjusted estimation of the number of 2019 novel coronavirus cases in Wuhan, China",doi.org/10.1101/2020.02.18.20024281,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>An outbreak of clusters of viral pneumonia due to a novel coronavirus (2019-nCoV / SARS-CoV-2) happened in Wuhan, Hubei Province in China in December 2019. Since the outbreak, several groups reported estimated R0 of Coronavirus Disease 2019 (COVID-19) and generated valuable prediction for the early phase of this outbreak. After implementation of strict prevention and control measures in China, new estimation is needed. An infectious disease dynamics SEIR (Susceptible, Exposed, Infectious and Removed) model was applied to estimate the epidemic trend in Wuhan, China under two assumptions of Rt. In the first assumption, Rt was assumed to maintain over 1. The estimated number of infections would continue to increase throughout February without any indication of dropping with Rt = 1.9, 2.6 or 3.1. The number of infections would reach 11,044, 70,258 and 227,989, respectively, by 29 February 2020. In the second assumption, Rt was assumed to gradually decrease at different phases from high level of transmission (Rt = 3.1, 2.6 and 1.9) to below 1 (Rt = 0.9 or 0.5) owing to increasingly implemented public heath intervention. Several phases were divided by the dates when various levels of prevention and control measures were taken in effect in Wuhan. The estimated number of infections would reach the peak in late February, which is 58,077-84,520 or 55,869-81,393. Whether or not the peak of the number of infections would occur in February 2020 may be an important index for evaluating the sufficiency of the current measures taken in China. Regardless of the occurrence of the peak, the currently strict measures in Wuhan should be continuously implemented and necessary strict public health measures should be applied in other locations in China with high number of COVID-19 cases, in order to reduce Rt to an ideal level and control the infection.</jats:p>",2020-02-23,"['Huwen Wang', 'Zezhou Wang', 'Yinqiao Dong', 'Ruijie Chang', 'Chen Xu', 'Xiaoyue Yu', 'Shuxian Zhang', 'Lhakpa Tsamlag', 'Meili Shang', 'Jinyan Huang', 'Ying Wang', 'Gang Xu', 'Tian Shen', 'Xinxin Zhang', 'Yong Cai']",,,,True
36521caf90f471c9da1a4e84f8562440d73ead9a,medrxiv,Estimation of the epidemic properties of the 2019 novel coronavirus: A mathematical modeling study,doi.org/10.1101/2020.02.18.20024315,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background The 2019 novel Coronavirus (COVID-19) emerged in Wuhan, China in December 2019 and has been spreading rapidly in China. Decisions about its pandemic threat and the appropriate level of public health response depend heavily on estimates of its basic reproduction number and assessments of interventions conducted in the early stages of the epidemic.  Methods We conducted a mathematical modeling study using five independent methods to assess the basic reproduction number (R0) of COVID-19, using data on confirmed cases obtained from the China National Health Commission for the period 10th January to 8th February. We analyzed the data for the period before the closure of Wuhan city (10th January to 23rd January) and the post-closure period (23rd January to 8th February) and for the whole period, to assess both the epidemic risk of the virus and the effectiveness of the closure of Wuhan city on spread of COVID-19.  Findings Before the closure of Wuhan city the basic reproduction number of COVID-19 was 4.38 (95% CI: 3.63-5.13), dropping to 3.41 (95% CI: 3.16-3.65) after the closure of Wuhan city. Over the entire epidemic period COVID-19 had a basic reproduction number of 3.39 (95% CI: 3.09-3.70), indicating it has a very high transmissibility.  Interpretation COVID-19 is a highly transmissible virus with a very high risk of epidemic outbreak once it emerges in metropolitan areas. The closure of Wuhan city was effective in reducing the severity of the epidemic, but even after closure of the city and the subsequent expansion of that closure to other parts of Hubei the virus remained extremely infectious. Emergency planners in other cities should consider this high infectiousness when considering responses to this virus.</jats:p>",2020-02-20,"['Jinghua Li', 'Yijing Wang', 'Stuart Gilmour', 'Mengying Wang', 'Daisuke Yoneoka', 'Ying Wang', 'Xinyi You', 'Jing Gu', 'Chun Hao', 'Liping Peng', 'Zhicheng Du', 'Dong Roman Xu', 'Yuantao Hao']",,,,True
4609a2dd3568a7241548b7303e0d836e33d4d5ca,medrxiv,Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19),doi.org/10.1101/2020.02.18.20024364,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>BACKGROUND The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health, which has been declared a public health emergency of international concern (PHEIC) by the WHO. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. METHODS We retrospectively reviewed the counts of total T cells, CD4+, CD8+ T cell subsets, and serum cytokine concentration from inpatient data of 522 patients with laboratory-confirmed COVID-19, admitted into two hospitals in Wuhan from December 2019 to January 2020, and 40 healthy controls, who came to the hospitals for routine physical examination. In addition, the expression of T cell exhaustion markers PD-1 and Tim-3 were measured by flow cytometry in the peripheral blood of 14 COVID-19 cases.  RESULTS The number of total T cells, CD4+ and CD8+ T cells were dramatically reduced in COVID-19 patients, especially among elderly patients (≥60 years of age) and in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8+T cells or CD4+T cells lower than 800/μL, 300/μL, or 400/μL, respectively, are negatively correlated with patient survival. Statistical analysis demonstrated that T cell numbers are negatively correlated to serum IL-6, IL-10 and TNF-α concentration, with patients in decline period showing reduced IL-6, IL-10 and TNF-α concentrations and restored T cell counts. Finally, T cells from COVID-19 patients have significantly higher levels of the exhausted marker PD-1 as compared to health controls. Moreover, increasing PD-1 and Tim-3 expression on T cells could be seen as patients progressed from prodromal to overtly symptomatic stages, further indicative of T cell exhaustion.  CONCLUSIONS T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients, with total T cells, CD8+T cells CD4+T cells counts lower than 800/μL, 300/μL, and 400/μL, respectively, may still require aggressive intervention even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.</jats:p>",2020-02-20,"['Bo Diao', 'Chenhui Wang', 'Yingjun Tan', 'Xiewan Chen', 'Ying Liu', 'Lifeng Ning', 'Li Chen', 'Min Li', 'Yueping Liu', 'Gang Wang', 'Zilin Yuan', 'Zeqing Feng', 'Yuzhang Wu', 'Yongwen Chen']",,,,True
fc7a6b5d1852c5ecce2d20fd0d73d5f957ed7055,medrxiv,Effective containment explains sub-exponential growth in confirmed cases of recent COVID-19 outbreak in Mainland China,doi.org/10.1101/2020.02.18.20024414,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The recent outbreak of COVID-19 in Mainland China is characterized by a distinctive algebraic, sub-exponential increase of confirmed cases with time during the early phase of the epidemic, contrasting an initial exponential growth expected for an unconstrained outbreak with sufficiently large reproduction rate. Although case counts vary significantly between affected provinces in Mainland China, the scaling law t^μ is surprisingly universal, with a range of exponents μ = 2.1 ± 0.3. The universality of this behavior indicates that, in spite of social, regional, demographical, geographical, and socio-economical heterogeneities of affected Chinese provinces, this outbreak is dominated by fundamental mechanisms that are not captured by standard epidemiological models. We show that the observed scaling law is a direct consequence of containment policies that effectively deplete the susceptible population. To this end we introduce a parsimonious model that captures both, quarantine of symptomatic infected individuals as well as population wide isolation in response to mitigation policies or behavioral changes. For a wide range of parameters, the model reproduces the observed scaling law in confirmed cases and explains the observed exponents. Quantitative fits to empirical data permit the identification of peak times in the number of asymptomatic or oligo-symptomatic, unidentified infected individuals, as well as estimates of local variations in the basic reproduction number. The model implies that the observed scaling law in confirmed cases is a direct signature of effective contaiment strategies and/or systematic behavioral changes that affect a substantial fraction of the susceptible population. These insights may aid the implementation of containment strategies in potential export induced COVID-19 secondary outbreaks elsewhere or similar future outbreaks of other emergent infectious diseases.</jats:p>",2020-02-20,"['Benjamin F Maier', 'Dirk Brockmann']",,,,True
ba1c4c0de19352d0b9ed7db6199803b621f0a8f2,medrxiv,"Psychological responses, behavioral changes and public perceptions during the early phase of the COVID-19 outbreak in China: a population based cross-sectional survey",doi.org/10.1101/2020.02.18.20024448,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: To investigate psychological and behavioral responses to the threat of SARS-CoV-2 infections and their associations with public perceptions in China  Design: Cross sectional population-based telephone survey via random digital dialing between 1 and 10 February, 2020 Setting: Wuhan (the epicentre and quarantined city), and Shanghai (a typical major city with close transportation link with Wuhan) Participants: Random sample of 510 residents in Wuhan and 501 residents in Shanghai aged above 18 Main outcome measures: Anxiety (measured by the 7-item generalized anxiety disorder [GAD-7] scale), recommended and avoidance behaviors (engaged in all six behaviors such as increasing surface cleaning and reducing going out). Results: The prevalence rates of moderate or severe anxiety (score ≥10 on GAD-7) were 32.7% (n=167) among Wuhan participants and 20.4% (n=102) among Shanghai participants. 78.6% (n=401) of Wuhan participants and 63.9% (n=320) of Shanghai participants had carried out all six precautionary behaviors. For both measures, Wuhan participants were more responsive to the outbreak (p&lt;0.001). Controlling for personal characteristics, logistic regression results suggested that risks of moderate or severe anxiety were positively associated with perceived susceptibility (odds ratio 1.6, 95% confidence interval 1.3-1.8) and severity of the disease (1.6, 1.4-1.9) and confusion about information reliability (1.6, 1.5-1.9). Having confidence in taking measures to protect oneself against the disease was associated with a lower risk (0.6, 0.5-0.7). The strongest predictor of behavioral change was perceived severity (1.2, 1.1-1.4), followed by confusion about information reliability (1.1, 1.0-1.3).   Conclusions: Psychological and behavioral responses to COVID-19 have been dramatic during the rising phase of the outbreak. Our results support efforts for timely dissemination of accurate and reliable information to address the high anxiety level.</jats:p>",2020-02-20,"['Mengcen Qian', 'Qianhui Wu', 'Peng Wu', 'Zhiyuan Hou', 'Yuxia Liang', 'Benjamin J Cowling', 'Hongjie Yu']",,,,True
537009c0181c3269f40753f75ddca4d17ae8abae,medrxiv,Estimating the cure rate and case fatality rate of the ongoing epidemic COVID-19,doi.org/10.1101/2020.02.18.20024513,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The epidemic caused by the novel coronavirus COVID-19 in Wuhan at the end of 2019 has become an urgent public event of worldwide concern. However, due to the changing data of the epidemic, there is no scientific estimate of the cure rate and case fatality rate of the epidemic. This study proposes a method to estimate the cure rate and case fatality rate of COVID-19. The ratio of cumulative discharges on a given day to the sum of cumulative discharges on a given day and cumulative deaths before j days is used to estimate the cure rate. Moreover, the case fatality ratio can also be estimated. After simulation calculations, j is statistically appropriate when it is 8-10, and it is also clinically appropriate. When j is 9, based on the available data, it is inferred that the cure rate of this epidemic is about 93% and the case fatality rate is about 7%. This method of estimating the cure rate can be used to evaluate the effectiveness of treatment in different medical schemes and different regions, and has great value and significance for decision-making in the epidemic.</jats:p>",2020-02-20,"['Ying Diao', 'Xiaoyun Liu', 'Tao Wang', 'Xiaofei Zeng', 'Chen Dong', 'Changlong Zhou', 'Yuanming Zhang', 'Xuan She', 'Dingfu Liu', 'Zhongli Hu']",,,,True
9bf1677e5f822110e736076a4ba6960a80f2f348,medrxiv,Clinical characteristics of 50466 patients with 2019-nCoV infection,doi.org/10.1101/2020.02.18.20024539,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: We aim to summarize reliable evidences of evidence-based medicine for the treatment and prevention of the 2019 novel coronavirus (2019-nCoV) by analyzing all the published studies on the clinical characteristics of patients with 2019-nCoV. Methods: PubMed, Cochrane Library, Embase, and other databases were searched. Several studies on the clinical characteristics of 2019-nCoV infection were collected for Meta-analysis. Results: Ten studies were included in Meta-analysis, including a total number of 50466 patients with 2019-nCoV infection. Meta-analysis shows that, among these patients, the incidence of fever was 89.1%, the incidence of cough was 72.2%, and the incidence of muscle soreness or fatigue was 42.5%. The incidence of acute respiratory distress syndrome (ARDS) was 14.8%, the incidence of abnormal chest computer tomography (CT) was 96.6%, the percentage of severe cases in all infected cases was 18.1%, and the case fatality rate of patients with 2019-nCoV infection was 4.3%. Conclusion: Fever and cough are the most common symptoms in patients with 2019-nCoV infection, and most of these patients have abnormal chest CT examination. Several people have muscle soreness or fatigue as well as ARDS. Diarrhea, hemoptysis, headache, sore throat, shock, and other symptoms only occur in a small number of patients. The case fatality rate of patients with 2019-nCoV infection is lower than that of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS).</jats:p>",2020-02-23,"['Pengfei Sun', 'Shuyan Qie', 'Zongjan Liu', 'Jizhen Ren', 'Jianing Jianing Xi']",,,,True
672ca9b6e50e26c49fc7be2ef3b4f685badf9db1,medrxiv,Modeling and Prediction of the 2019 Coronavirus Disease Spreading in China Incorporating Human Migration Data,doi.org/10.1101/2020.02.18.20024570,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>This study integrates the daily intercity migration data with the classic Susceptible-Exposed-Infected-Removed (SEIR) model to construct a new model suitable for describing the dynamics of epidemic spreading of Coronavirus Disease 2019 (COVID-19) in China. Daily intercity migration data for 367 cities in China are collected from Baidu Migration, a mobile-app based human migration tracking data system. Historical data of infected, recovered and death cases from official source are used for model fitting. The set of model parameters obtained from best data fitting using a constrained nonlinear optimization procedure is used for estimation of the dynamics of epidemic spreading in the coming weeks. Our results show that the number of infections in most cities in China will peak between mid February to early March 2020, with about 0.8%, less than 0.1% and less than 0.01% of  the population eventually infected in Wuhan, Hubei Province and the rest of China, respectively.</jats:p>",2020-02-20,"['Choujun Zhan', 'Chi K. Tse', 'Yuxia Fu', 'Zhikang Lai', 'Haijun Zhang']",,,,True
a09c1ad0f05bbcc256cd667ad7411e6690134370,medrxiv,Association of Population Migration and Coronavirus Disease 2019 Epidemic Control,doi.org/10.1101/2020.02.18.20024661,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background and Objective To analyze the impact of different patterns of migration flow in two cities, Hefei and Shenzhen, on the epidemic and disease control of Coronavirus Disease 2019 (COVID-19), in order to provide insight for making differentiated controlling policies. Methods We collected demographic and epidemiological information of confirmed COVID-19 cases in Hefei and Shenzhen between January 19 and February 11, 2020, from data officially published by the provincial and municipal Centers for Disease Control and Prevention (CDC). From these data we calculated basic reproduction number R0 to reflect the rate of spread of COVID-19 in these cities. Aggregated data of population migration during the same period was extracted from Baidu Migration. The change of R0 in the two cites were analyzed and compared. Spearman correlation analysis between R0 and population inflow from epidemic focus were performed. Results A total of 157 confirmed cases was identified in Hefei by 24:00 February 11, 2020, with an average age of 44.4±15.6 years, 74 female (47.1%) and 386 confirmed cases were identified in Shenzhen, with an average age of 45.15±17.99 years, 202 female (52.3%). Significant difference in the proportion of imported cases between the two cities was observed (Hefei vs Shenzhen, 24.2% vs 74.9%, p=0.000). Before January 31 2020, during the initial stage of the Level 1 Response to Major Public Health Emergencies, there was no significant association observed in Shenzhen between R0 and the proportion of population inflow from the epidemic focus (P =0.260, r=-0.452); meanwhile in Hefei, such association was strong (P =0.000, r=1.0). However, after the initial stage of response, the situation reversed. A weak association was observed in Shenzhen between be R0 and the proportion of population inflow from the epidemic focus (P=0.073, r=0.536) but not in Hefei (P =0.498, r=0.217). Conclusion Following Level 1 Response, consistent decline of R0 of COVID-19 was observed in both Hefei and Shenzhen. Different patterns of disease spread were observed in the two cities, driven by different patterns of population migration. This indicated that population migration should be taken into consideration when we set controlling policy of a novel infectious disease.</jats:p>",2020-02-20,"['Yu Ding', 'Sihui Luo', 'Xueying Zheng', 'Ping Ling', 'Tong Yue', 'Zhirong Liu', 'Jianping Weng']",,,,True
f9a53c7bcebadd94b10a3943ab484418440b2a71,medrxiv,Early Phylogenetic Estimate Of The Effective Reproduction Number Of 2019-nCoV,doi.org/10.1101/2020.02.19.20024851,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>To reconstruct the evolutionary dynamics of the 2019 novel coronavirus, 52 2019−nCOV genomes available on 04 February 2020 at GISAID were analysed. The two models used to estimate the reproduction number (coalescent−based exponential growth and a birth−death skyline method) indicated an estimated mean evolutionary rate of 7.8 x 10−4 subs/site/year (range 1.1x10−4−15x10−4).  The estimated R value was 2.6 (range 2.1−5.1), and increased from 0.8 to 2.4 in December 2019. The estimated mean doubling time of the epidemic was between 3.6 and 4.1 days. This study proves the usefulness of phylogeny in supporting the surveillance of emerging new infections even as the epidemic is growing.</jats:p>",2020-02-23,"['Alessia Lai', 'Annalisa Bergna', 'Carla Acciarri', 'Massimo Galli', 'Gianguglielmo Zehender']",,,,False
f3ed3f152cafd3de82ba4a1dc72ba3aa0207cd07,medrxiv,Comparative study of the lymphocyte change between COVID-19 and non-COVID-19 pneumonia cases suggesting uncontrolled inflammation might not be the main reason of tissue injury,doi.org/10.1101/2020.02.19.20024885,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The authors have withdrawn this manuscript because the statistical methods in our manuscript need to be modified and we are going to improve the statistical methods and try to give more precise model. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.</jats:p>",2020-02-23,"['Yishan Zheng', 'Zhen Huang', 'Guoping Ying', 'Xia Zhang', 'Wei Ye', 'Zhiliang Hu', 'Chunmei Hu', 'Hongxia Wei', 'Yi Zeng', 'Yun Chi', 'Cong Cheng', 'Feishen Lin', 'Hu Lu', 'Lingyan Xiao', 'Yan Song', 'Chunming Wang', 'Yongxiang Yi', 'Lei Dong']",,,,False
f3ff1ecae96700f41b83d2a034a3a959428388b0,medrxiv,"The cross-sectional study of hospitalized coronavirus disease 2019 patients in Xiangyang, Hubei province",doi.org/10.1101/2020.02.19.20025023,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Summary   Objective To describe the epidemiological and clinical characteristics of the Coronavirus Disease 2019 (COVID-19) hospitalized patients and to offer suggestions to the urgent needs of COVID-19 prevention, diagnosis and treatment.      Methods We included 102 confirmed COVID-19 cases hospitalized in Xiangyang No.1 peoples hospital, Hubei, China until Feb 9th, 2020. Demographic data, laboratory findings and chest computed tomographic (CT) images were obtained and analyzed.       Findings All cases were confirmed by real-time RT-PCR, including 52 males and 50 females with a mean age of 50.38 years (SD 16.86). Incubation time ranged from one to twenty days with a mean period of 8.09 days (SD 4.99). Fever (86[84.3%] of 102 patients), cough (58[57%]), fatigue (28[27%]), shortness of breath (24[23%]), diarrhea (15[15%]), expectoration (13[12%]), inappetence (11[10%]) were common clinical manifestations. We observed a decreased blood leukocyte count and lymphopenia in 21 (20.6%) and 56 (54.9%) patients, respectively. There were 66 (68%) of 97 patients with elevated C-reactive protein levels and 49 (57.6%) of 85 with increased erythrocytes sedimentation rate. Higher levels of procalcitonin and ferritin were observed in 19 (25.3%) of 75 and 12 (92.3%) of 13 patients, respectively. Eight patients were admitted to intensive care unit (ICU), six developed respiratory failure, three had multiple organ failure and three died. The cumulative positivity rate over three rounds of real-time RT-PCR was 96%. One-hundred patients were found with typical radiological abnormalities in two rounds of chest CT scans, indicating a 98% consistency with real-time RT-PCR results.      Interpretation Most COVID-19 patients in Xiangyang were secondary cases without sex difference, and the rate of severe cases and death was low. Middle-to-old-age individuals were more susceptible to the virus infection and the subsequent development of severe/fatal consequences. The average incubation period was longer among our patients. We recommend prolonging the quarantine period to three weeks. Three times real-time RT-PCR plus two times CT scans is a practical clinical diagnosis strategy at present and should be used to increase the accuracy of diagnosis, thereby controlling the source of infection more effectively.      Key Words SARS-CoV-2; COVID-19; epidemiological and clinical features; diagnosis</jats:p>",2020-02-23,"['Jinwei Ai', 'Junwen Chen', 'Yong Wang', 'Xiaoyun Liu', 'Wufeng Fan', 'Gaojing Qu', 'Meiling Zhang', 'Shengduo Polo Pei', 'Bowen Tang', 'Shuai Yuan', 'Yang Li', 'Lisha Wang', 'Guoxin Huang', 'Bin Pei']",,,,True
eb8ac60527db35b10881cb4fd86b8a6e21983d02,medrxiv,"A descriptive study of the impact of diseases control and prevention on the epidemics dynamics and clinical features of SARS-CoV-2 outbreak in Shanghai, lessons learned for metropolis epidemics prevention",doi.org/10.1101/2020.02.19.20025031,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: To describe and evaluate the impact of diseases control and prevention on epidemics dynamics and clinical features of SARS-CoV-2 outbreak in Shanghai.  Design: A retrospective descriptive study  Setting: China  Participants: Epidemiology information was collected from publicly accessible database. 265 patients admitted to Shanghai Public Health Center with confirmed COVID-19 were enrolled for clinical features analysis.  Main outcome measure: Prevention and control measures taken by Shanghai government,  epidemiological, demographic, clinical, laboratory and radiology data were collected. Weibull distribution, Chi-square test, Fisher's exact test, t test or Mann-Whitney U test were used in statistical analysis.   Results: COVID-19 transmission rate within Shanghai had reduced over 99% than previous speculated, and the exponential growth has been stopped so far. Epidemic was characterized by the first stage mainly composed of imported cases and the second stage where &gt;50% of cases were local. The incubation period was 6.4 (95% CI 5.3 to 7.6) days and the mean onset-admission interval was 5.5 days (95% CI, 5.1 to 5.9). Median time for COVID-19 progressed to severe diseases were 8.5 days (IQR: 4.8-11.0 days). By February 11th, proportion of patients being mild, moderate, severe and critically ill were 1.9%(5/265), 89.8%(238/265), 3.8%(10/265), 4.5%(12/265), respectively; 47 people in our cohort were discharged, and 1 patient died.  Conclusion: Strict controlling of the transmission rate at the early stage of an epidemic in metropolis can quickly prohibit the spread of the diseases. Controlling local clusters is the key to prevent outbreaks from imported cases. Most COVID-19 severe cases progressed within 14 days of disease onset. Multiple systemic laboratory abnormalities had been observed before significant respiratory dysfunction.   Keyword: COVID-19, SARS-CoV-2, epidemics dynamics, diseases control, clinical features</jats:p>",2020-02-23,"['Hongzhou Lu', 'Jingwen Ai', 'Yinzhong Shen', 'Yang Li', 'Tao Li', 'Xian Zhou', 'Haocheng Zhang', 'Qiran Zhang', 'Yun Ling', 'Sheng Wang', 'Hongping Qu', 'Yuan Gao', 'Yingchuan Li', 'Kanglong Yu', 'Duming Zhu', 'Hecheng Zhu', 'Rui Tian', 'Mei Zeng', 'Qiang Li', 'Yuanlin Song', 'Xiangyang Li', 'Jinfu Xu', 'Jie Xu', 'Enqiang Mao', 'Bijie Hu', 'Xin Li', 'Lei Zhu', 'Wenhong Zhang']",,,,True
0e8fa9095bdee851efc5b262ad11d7a2b72b02ec,medrxiv,"Trends and prediction in daily incidence of novel coronavirus infection in China, Hubei Province and Wuhan City: an application of Farr law",doi.org/10.1101/2020.02.19.20025148,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: The recent outbreak of novel coronavirus (2019-nCoV) has infected tens of thousands of patients in China. Studies have forecasted future trends of the incidence of 2019-nCoV infection, but appeared unsuccessful. Farr law is a classic epidemiology theory/practice for predicting epidemics. Therefore, we used and validated a model based on Farr law to predict the daily-incidence of 2019-nCoV infection in China and 2 regions of high-incidence.  Methods: We extracted the 2019-nCoV incidence data of China, Hubei Province and Wuhan City from websites of the Chinese and Hubei health commissions. A model based on Farr law was developed using the data available on Feb. 8, 2020, and used to predict daily-incidence of 2019-nCoV infection in China, Hubei Province and Wuhan City afterward.  Results: We observed 50,995 (37001 on or before Feb. 8) incident cases in China from January 16 to February 15, 2020. The daily-incidence has peaked in China, Hubei Providence and Wuhan City, but with different downward slopes. If no major changes occur, our model shows that the daily-incidence of 2019-nCoV will drop to single-digit by February 25 for China and Hubei Province, but by March 8 for Wuhan city. However, predicted 75% confidence intervals of daily-incidence in all 3 regions of interest had an upward trend. The predicted trends overall match the prospectively-collected data, confirming usefulness of these models. Conclusions: This study shows the daily-incidence of 2019-nCoV in China, Hubei Province and Wuhan City has reached the peak and was decreasing. However, there is a possibility of upward trend.</jats:p>",2020-02-23,"['Jie Xu', 'Yajiao Cheng', 'Xiaoling Yuan', 'Wei V. Li', 'Lanjing Zhang']",,,,False
712f1a74a5083d690832eed5fd9ff16a04434d8d,medrxiv,Rapid Detection of Novel Coronavirus (COVID-19) by Reverse Transcription-Loop-Mediated Isothermal Amplification,doi.org/10.1101/2020.02.19.20025155,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Novel Corona virus (COVID-19 or 2019-nCoV) is an emerging global health concern that requires a rapid diagnostic test. Quantitative reverse transcription PCR (qRT-PCR) is currently the standard for COVID-19 detection; however, Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) may allow for faster and cheaper field based testing at point-of-risk. The objective of this study was to develop a rapid screening diagnostic test that could be completed in under 30 minutes. Simulated patient samples were generated by spiking serum, urine, saliva, oropharyngeal swabs, and nasopharyngeal swabs with a portion of the COVID-19 nucleic sequence. The samples were tested using RT-LAMP as well as by conventional qRT-PCR. Specificity of the RT-LAMP was evaluated by also testing against other related coronaviruses. RT-LAMP specifically detected COVID-19 in simulated patient samples. This test was performed in under 30 minutes. This approach could be used for monitoring of exposed individuals or potentially aid with screening efforts in the field and potential ports of entry.</jats:p>",2020-02-24,"['Laura E Lamb', 'Sarah N Bartolone', 'Elijah Ward', 'Michael B Chancellor']",,,,True
9cc5bebada7ff4894c2ee6454f09d9b8ea73e6e6,medrxiv,"Estimating the risk of 2019 Novel Coronavirus death during the course of the outbreak in China, 2020",doi.org/10.1101/2020.02.19.20025163,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Since the first case of Novel Coronavirus (2019-nCov) was identified in December 2019 in Wuhan City, China, the number of cases continues to grow across China and  multiple cases have been exported to other countries. The cumulative number of reported deaths is at 637 as of February 7, 2020. Here we statistically estimated the time-delay adjusted death risk for Wuhan as well as for China excluding Wuhan to interpret the current severity of the epidemic in China. We found that the latest estimates of the death risk in Wuhan could be as high as 20% in the epicenter of the epidemic whereas we estimate it ~1% in the relatively mildly-affected areas. Because the elevated death risk estimates are likely associated with a breakdown of the medical/health system, enhanced public health interventions including social distancing and movement restrictions should be effectively implemented to bring the epidemic under control.</jats:p>",2020-02-23,"['Kenji Mizumoto', 'Gerardo Chowell']",,,,False
3c94f582610453b6c1389c3a5d6ad57bcf0ba033,medrxiv,"Clinical characteristics of 25 death cases infected with COVID-19 pneumonia: a retrospective review of medical records in a single medical center, Wuhan, China",doi.org/10.1101/2020.02.19.20025239,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Summary Background The pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2) is a highly infectious disease, which was occurred in Wuhan, Hubei Province, China in December 2019. As of February 13, 2020, a total of 59883 cases of COVID-19 in China have been confirmed and 1368 patients have died from the disease. However, the clinical characteristics of the dyed patients were still not clearly clarified. This study aims to summarize the clinical characteristics of death cases with COVID-19 and to identify critically ill patients of COVID-19 early and reduce their mortality.   Methods The clinical records, laboratory findings and radiologic assessments included chest X-ray or computed tomography were extracted from electronic medical records of 25 died patients with COVID-19 in Renmin Hospital of Wuhan University from Jan 14 to Feb 13, 2020. Two experienced clinicians reviewed and abstracted the data.  Findings The mean age of the dead was 71.48  years, the average course of the disease was 10.56  days, all patients eventually died of respiratory failure. All of those who died had underlying diseases, the most common of which was hypertension (16/25, 64%), followed by diabetes (10/25, 40%), heart diseases (8/25, 32%), kidney diseases (5/25, 20%), cerebral infarction (4/25, 16%), chronic obstructive pulmonary disease (COPD, 2/25, 8%), malignant tumors (2/25, 8%) and acute pancreatitis (1/25, 4%). The most common organ damage outside the lungs was the heart, followed by kidney and liver. In the patients' last examination before death, white blood cell and neutrophil counts were elevated in 17 patients (17/25, 68%) and 18 patients (18/25, 72%), lymphocyte counts were decreased in 22  patients (22/25, 88%). Most patients' PCT, CRP and SAA levels were elevated, the percentages were 90.5% (19/21), 85% (19/20) and 100% (21/21) respectively. The levels of the last test of neutrophils (15/16, 93.8%), PCT (11/11, 100%), CRP (11/13, 84.6%), cTnI (8/9, 88.9%), D-Dimer (11/12, 91.6%) and LDH (9/9, 100%) were increased as compared to the first test, while the levels of lymphocytes were decreased (14/16, 87.5%).   Interpretation The age and underlying diseases (hypertension, diabetes, etc.) were the most important risk factors for death of COVID-19 pneumonia. Bacterial infections may play an important role in promoting the death of patients. Malnutrition was common to severe patients. Multiple organ dysfunction can be observed, the most common organ damage  was lung, followed by heart, kidney and liver. The rising of neutrophils, SAA, PCT, CRP, cTnI, D-Dimer and LDH levels can be used as indicators of disease progression, as well as the decline of lymphocytes counts.</jats:p>",2020-02-25,"['Xun Li', 'Luwen Wang', 'Shaonan Yan', 'Fan Yang', 'Longkui Xiang', 'Jiling Zhu', 'Bo Shen', 'Zuojiong Gong']",,,,True
536dc3fc3226429da5bf028cc5563bf9ac5b6311,medrxiv,A Note on NCP Diagnosis Number Prediction Model,doi.org/10.1101/2020.02.19.20025262,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>In December 2019, pneumonia infected with the novel coronavirus burst in Wuhan, China. We aimed to use a mathematical model to predict number of diagnosed patients in future to ease anxiety on the emergent situation. In this retrospective, all diagnosis number from Jan 21 to Feb 10, 2020 reported from China was included and downloaded from WHO website. We develop a simple but accurate formula to predict the next day diagnosis number:N_i/N_(i-1) =〖(N_(i-1)/N_(i-2) )〗^α，where Ni is the total diagnosed patient till the ith day, and α was estimated as 0.904 at Feb 10. Based on this model, it is predicted that the rate of disease infection will decrease exponentially. The total number of infected people is limited; thus, the disease will have limited impact. However, new diagnosis will last to March.</jats:p>",2020-02-23,"['Yi Li', 'Xianhong Yin', 'Meng Liang', 'Xiaoyu Liu', 'Meng Hao', 'Yi Wang']",,,,True
1e45cd5feb7928bbc8bcd524d9c6b7adeae08a6b,medrxiv,"SARS-CoV-2 infection does not significantly cause acute renal injury: an analysis of 116 hospitalized patients with COVID-19 in a single hospital, Wuhan, China",doi.org/10.1101/2020.02.19.20025288,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Summary  Background Whether the patients with COVID-19 infected by SARS-CoV-2 would commonly develop acute renal function damage is a problem worthy of clinical attention. This study aimed to explore the effects of SARS-CoV-2 infection on renal function through analyzing the clinical data of 116 hospitalized COVID-19-confirmed patients.  Methods 116 hospitalized COVID-19-confirmed patients enrolled in this study were hospitalized in the Department of Infectious Diseases, Renmin Hospital of Wuhan University from January 14 to February 13, 2020. The recorded information includes demographic data, medical history, contact history, potential comorbidities, symptoms, signs, laboratory test results, chest computer tomography (CT) scans, and treatment measures. SARS-CoV-2 RNA in 53 urine sediments of enrolled patients was examined by real-time RT-PCR.  Findings 12 (10.8%) and 8 (7.2%) patients showed mild elevation of blood urea nitrogen or creatinine, and trace or 1+ albuminuria respectively in 111 COVID-19-confirmed patients without basic kidney disease. In addition, 5 patients with chronic renal failure (CRF) were undergone regular continuous renal replacement therapy (CRRT) were confirmed infection of SARS-CoV-2, and diagnosed as COVID-19. Beside the treatment of COVID-19, CRRT was also applied three times weekly. The course of treatment, the renal function indicators showed stable, without exacerbation of CRF, and pulmonary inflammation was gradually absorbed. All 5 patients with CRF were survived. Moreover, SARS-CoV-2 RNA in urine sediments was positive only in 3 patients from 48 cases without renal illness before, and one patient had a positive for SARS-CoV-2 ORF 1ab from 5 cases with CRF.  Interpretation Acute renal impairment was uncommon in COVID-19. SARS-CoV-2 infection does not significantly cause obvious acute renal injury, or aggravate CRF in the COVID-19 patients.</jats:p>",2020-02-23,"['Lunwen Wang', 'Xun Li', 'Hui Chen', 'Shaonan Yan', 'Yan Li', 'Dong Li', 'Zuojiong Gong']",,,,True
4e2bc97a6164191ba3d53abfa49ccd973aa80326,medrxiv,Early Prediction of Disease Progression in 2019 Novel Coronavirus Pneumonia Patients Outside Wuhan with CT and Clinical Characteristics,doi.org/10.1101/2020.02.19.20025296,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: To determine the predictive value of CT and clinical characteristics for short-term disease progression in patients with 2019 novel coronavirus pneumonia (NCP).  Materials and Methods: 224 patients with confirmed 2019 novel coronavirus (COVID-19) infection outside Wuhan who had chest CT examinations were retrospectively screened. Clinical data were obtained from electronic medical records. CT images were reviewed and scored for lesion distribution, lobe and segment involvement, ground-glass opacities, consolidation, and interstitial thickening. All included patients with moderate NCP were observed for at least 14 days from admission to determine whether they exacerbated to severe NCP (progressive group) or not (stable group). CT and clinical characteristics between the two groups were compared, and multivariate logistic regression and sensitivity analyses were performed to identify the risk factors for developing severe NCP.  Results: A total of 141 patients with moderate NCP were included, of which 15 (10.6%) patients developed severe NCP during hospitalization and assigned to the progressive group. Multivariate logistic regression analysis showed that higher neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR] and 95% confidence interval [CI], 1.26 [1.04-1.53]; P = 0.018) and CT severity score (OR and 95% CI, 1.25 [1.08-1.46]; P = 0.004) on admission were independent predictors for progression to severe NCP, and sensitivity analysis confirmed the consistent results in nonimported patients but not in imported patients. However, no significant difference in lung involvement was found on CT between imported and nonimported patients (all P &gt; 0.05). Patients who were admitted more than 4 days from symptom onset tended to have more severe lung involvement. Spearman correlation analysis showed the close association between CT severity score and inflammatory indexes (r = 0.17~0.47, all P &lt; 0.05). Conclusion: CT severity score was associated with inflammatory levels and higher NLR and CT severity score on admission were independent risk factors for short-term progression in patients with NCP outside Wuhan. Furthermore, early admission and surveillance by CT should be recommended to improve clinical outcomes.</jats:p>",2020-02-23,"['Zhichao Feng', 'Qizhi Yu', 'Shanhu Yao', 'Lei Luo', 'Junhong Duan', 'Zhimin Yan', 'Min Yang', 'Hongpei Tan', 'Mengtian Ma', 'Ting Li', 'Dali Yi', 'Ze Mi', 'Huafei Zhao', 'Yi Jiang', 'Zhenhu He', 'Huiling Li', 'Wei Nie', 'Yin Liu', 'Jing Zhao', 'Muqing Luo', 'Xuanhui Liu', 'Pengfei Rong', 'Wei Wang']",,,,True
345ef4262fd82c24fcd5be3ea7318254d523d074,medrxiv,Effectiveness of control strategies for Coronavirus Disease 2019: a SEIR dynamic modeling study,doi.org/10.1101/2020.02.19.20025387,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Since its first cases occurrence in Wuhan, China, the Coronavirus Disease 2019 (COVID-19) has been spreading rapidly to other provinces and neighboring countries. A series of intervention strategies have been implemented, but didn't stop its spread. Methods: Two mathematical models have been developed to simulate the current epidemic situation in the city of Wuhan and in other parts of China. Special considerations were given to the mobility of people for the estimation and forecast the number of asymptomatic infections, symptomatic infections, and the infections of super-spreading events (Isse).  Findings: The basic reproductive number (R0) was calculated for the period between 18 January 2020 and 16 February 2020: R0 declined from 5.75 to 1.69 in Wuhan and from 6.22 to 1.67 in the entire country (not including the Wuhan area). At the same time, Wuhan is estimated to observe a peak in the number of confirmed cases around 6 February 2020. The number of infected individuals in the entire country (not including the Wuhan area) peaked around February 3. The results also show that the peak of new asymptomatic cases per day in Wuhan occurred on February 6, and the peak of new symptomatic infections have occurred on February 3. Concurrently, while the number of confirmed cases nationwide would continue to decline, the number of real-time COVID-19 inpatients in Wuhan has reached a peak of 13,030 on February 14 before it decreases. The model further shows that the COVID-19 cases will gradually wane by the end of April 2020, both in Wuhan and the other parts of China. The number of confirmed cases would reach the single digit on March 27 in Wuhan and March 19 in the entire country. The five cities with top risk index in China with the exclusion of Wuhan are: Huanggang, Xiaogan, Jingzhou, Chongqing, and Xiangyang city. Interpretations: Although the national peak time has been reached, a significant proportion of asymptomatic patients and the infections of super-spreading events (Isse) still exist in the population, indicating the potential difficulty for the prevention and control of the disease. As the Return-to-Work tide is approaching and upgrading, further measures (e.g., escalatory quarantine, mask wearing when going out, and sit apart when taking vehicles) will be particularly crucial to stop the COVID-19 in other cities outside of Wuhan.</jats:p>",2020-02-23,"['Jinhua Pan', 'Ye Yao', 'Zhixi Liu', 'Mengyi Li', 'Ying Wang', 'Weizhen Dong', 'Haidong Kan', 'Weibing Wang']",,,,False
84391aedfdbe714cb4428d48fa2d85a3ca8dcbb2,medrxiv,"Generalized anxiety disorder, depressive symptoms and sleep quality during COVID-19 epidemic in China: a web-based cross-sectional survey",doi.org/10.1101/2020.02.19.20025395,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: China has been severely affected by COVID-19 (Corona Virus Disease 2019) since December, 2019. This study aimed to assess the population mental health burden during the epidemic, and to explore the potential influence factors. Methods: Using a web-based cross-sectional survey, we collected data from 7,236 self-selected volunteers assessed with demographic information, COVID-19 related knowledge, Generalized Anxiety Disorder-7 (GAD-7), Center for Epidemiology Scale for Depression (CES-D), and Pittsburgh Sleep Quality Index (PSQI). Logistic regressions were used to identify influence factors associated with mental health problem. Results: Of the total sample analyzed, the overall prevalence of GAD, depressive symptoms, and sleep quality were 35.1%, 20.1%, and 18.2%, respectively. Young people reported a higher prevalence of GAD and depressive symptoms than older people (P&lt;0.001). Compared with other occupational group, healthcare workers have the highest rate of poor sleep quality (P&lt;0.001). Multivariate logistic regression showed that age (&lt; 35 years) and times to focus on the COVID-19 (≥ 3 hours per day) were associated with GAD, and healthcare workers were associated with poor sleep quality. Conclusions: Our study identified a major mental health burden of the public during COVID-19 epidemic in China. Young people, people who spent too much time on the epidemic, and healthcare workers were at high risk for mental illness. Continuous surveillance and monitoring of the psychological consequences for outbreaks should become routine as part of preparedness efforts worldwide.</jats:p>",2020-02-23,"['Yeen Huang', 'Ning Zhao']",,,,False
95688a7f321e4fc9cce4af03c8e3eb8e7ad8f935,medrxiv,The serial interval of COVID-19 from publicly reported confirmed cases,doi.org/10.1101/2020.02.19.20025452,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>As a novel coronavirus (COVID-19) continues to emerge throughout China and threaten the globe, its transmission characteristics remain uncertain. Here, we analyze the serial intervals-the time period between the onset of symptoms in an index (infector) case and the onset of symptoms in a secondary (infectee) case-of 468 infector-infectee pairs with confirmed COVID-19 cases reported by health departments in 18 Chinese provinces between January 21, 2020, and February 8, 2020. The reported serial intervals range from -11 days to 20 days, with a mean of 3.96 days (95% confidence interval: 3.53-4.39), a standard deviation of 4.75 days (95% confidence interval: 4.46-5.07), and 12.1% of reports indicating pre-symptomatic transmission.</jats:p>",2020-02-23,"['Zhanwei Du', 'Xiaoke Xu', 'Ye Wu', 'Lin Wang', 'Benjamin J Cowling', 'Lauren Ancel Meyers']",,,,True
ccd7721822cb7cf73f213ca0bbceb7a681e048a0,medrxiv,Novel Coronavirus 2019 (Covid-19) epidemic scale estimation: topological network-based infection dynamic model,doi.org/10.1101/2020.02.20.20023572,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Backgrounds: An ongoing outbreak of novel coronavirus pneumonia (Covid-19) hit Wuhan and hundreds of cities, 29 territories globally. We present a method for scale estimation in dynamic while most of the researchers used static parameters.  Methods: We use historical data and the SEIR model for important parameters assumption. And according to the timeline, we use dynamic parameters for infection topology network building. Also, the migration data is used for the Non-Wuhan area estimation which can be cross-validated for the Wuhan model. All data are from the public.  Results: The estimated number of infections is 61,596 (95%CI: 58,344.02-64,847.98) by 25 Jan in Wuhan. And the estimation number of the imported cases from Wuhan of Guangzhou was 170 (95%CI: 161.27-179.26), infection scale in Guangzhou is 315 (95%CI: 109.20-520.79), while the imported cases are 168 and the scale of the infection is 339 published by the authority.  Conclusions: Using dynamic network models and dynamic parameters for different time periods is an effective way of infection scale modeling.</jats:p>",2020-02-23,"['Keke Tang', 'Yining Huang', 'Meilian Chen']",,,,False
d37a760a6ae9f4df3da850e9a71b88d340c54588,medrxiv,COVID-19 in Wuhan: Immediate Psychological Impact on 5062 Health Workers,doi.org/10.1101/2020.02.20.20025338,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>BACKGROUND:  The outbreak of COVID-19 has laid unprecedented psychological stress on health workers (HWs). We aimed to assess the immediate psychological impact on HWs at Tongji Hospital in Wuhan, China. METHODS:  We conducted a single-center, cross-sectional survey of HWs via online questionnaires between February 8th and 10th, 2020. We evaluated stress, depression and anxiety by Impact of Event Scale-Revised (IES-R), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder 7-item (GAD-7), respectively. We also designed a questionnaire to assess the effect of psychological protective measures taken by Tongji Hospital. Multivariate logistic regression was used to identify predictors of acute stress, depression, and anxiety. RESULTS:  We received 5062 completed questionnaires (response rate, 77.1 percent). 1509 (29.8 percent), 681 (13.5 percent) and 1218 (24.1 percent) HWs reported stress, depression and anxiety symptoms. Women (hazard ratio[HR], 1.31; P=0.032), years of working&gt; 10 years (HR, 2.02; P&lt;0.001), concomitant chronic diseases (HR, 1.51; P&lt;0.001), history of mental disorders (HR, 3.27; P&lt;0.001), and family members or relatives confirmed or suspected (HR, 1.23; P=0.030) were risk factors for stress, whereas care provided by hospital and department administrators(odds ratio [OR], 0.76; P=0.024) and full coverage of all departments with protective measures (OR, 0.69; P=0.004) were protective factors. CONCLUSIONS:  Women and those who have more than 10 years of working, concomitant chronic diseases, history of mental disorders, and family members or relatives confirmed or suspected are susceptible to stress, depression and anxiety among HWs during the COVID-19 pandemic. Psychological protective measures implemented by the hospital could be helpful.</jats:p>",2020-02-23,"['Zhou Zhu', 'Shabei Xu', 'Hui Wang', 'Zheng Liu', 'Jianhong Wu', 'Guo Li', 'Jinfeng Miao', 'Chenyan Zhang', 'Yuan Yang', 'Wenzhe Sun', 'Suiqiang Zhu', 'Yebin Fan', 'Junbo Hu', 'Jihong Liu', 'Wei Wang']",,,,True
f854d7b750541d65c48df953a65028a50ce57881,medrxiv,"ACP risk grade: a simple mortality index for patients with confirmed or suspected severe acute respiratory syndrome coronavirus 2 disease (COVID-19) during the early stage of outbreak in Wuhan, China",doi.org/10.1101/2020.02.20.20025510,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) outbreaks in Wuhan, China, healthcare systems capacities in highly endemic areas have been overwhelmed. Approaches to efficient management are urgently needed and key to a quicker control of the outbreaks and casualties. We aimed to characterize the clinical features of hospitalized patients with confirmed or suspected COVID-19, and develop a mortality risk index for COVID-19 patients. Methods: In this retrospective one-centre cohort study, we included all the confirmed or suspected COVID-19 patients hospitalized in a COVID-19-designated hospital from January 21 to February 5, 2020. Demographic, clinical, laboratory, radiological and clinical outcome data were collected from the hospital information system, nursing records and laboratory reports. Results: Of 577 patients with at least one post-admission evaluation, the median age was 55 years (interquartile range [IQR], 39 - 66); 254 (44.0%) were men; 22.8% (100/438) were severe pneumonia on admission, and 37.7% (75/199) patients were SARS-CoV-2 positive. The clinical, laboratory and radiological data were comparable between positive and negative SARS-CoV-2 patients. During a median follow-up of 8.4 days (IQR, 5.8 - 12.0), 39 patients died with a 12-day cumulative mortality of 8.7% (95% CI, 5.9% to 11.5%). A simple mortality risk index (called ACP index), composed of Age and C-reactive Protein, was developed. By applying the ACP index, patients were categorized into three grades. The 12-day cumulative mortality in grade three (age ≥ 60 years and CRP ≥ 34 mg/L) was 33.2% (95% CI, 19.8% to 44.3%), which was significantly higher than those of grade two (age ≥ 60 years and CRP &lt; 34 mg/L; age &lt; 60 years and CRP ≥ 34 mg/L; 5.6% [95% CI, 0 to 11.3%]) and grade one (age &lt; 60 years and CRP &lt; 34 mg/L, 0%) (P &lt;0.001), respectively.  Conclusion: The ACP index can predict COVID-19 related short-term mortality, which may be a useful and convenient tool for quickly establishing a COVID-19 hierarchical management system that can greatly reduce the medical burden and therefore mortality in highly endemic areas.</jats:p>",2020-02-23,"['Jiatao Lu', 'Shufang Hu', 'Rong Fan', 'Zhihong Liu', 'Xueru Yin', 'Qiongya Wang', 'Qingquan Lv', 'Zhifang Cai', 'Haijun Li', 'Yuhai Hu', 'Ying Han', 'Hongping Hu', 'Wenyong Gao', 'Shibo Feng', 'Qiongfang Liu', 'Hui Li', 'Jian Sun', 'Jie Peng', 'Xuefeng Yi', 'Zixiao Zhou', 'Yabing Guo', 'Jinlin Hou']",,,,True
615645b4944137d6033f15257eabb0b3eafc2625,medrxiv,Clinical characteristics of 51 patients discharged from hospital with COVID-19 in Chongqing，China,doi.org/10.1101/2020.02.20.20025536,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Abstract Background：Since December 2019, Severe acute respiratory syndrome coronavirus 2（SARS-CoV-2）-infected disease (Coronavirus Disease 2019，COVID-19) emerged in Wuhan , China，and rapidly spread throughout China，even throughout the world. We try to describe the epidemiological and clinical characteristics of COVID-19 in non-Wuhan area，and explore its effective treatment.  Methods：Retrospective, single-center case series of the 51 hospitalized patients with confirmed COVID-19 at Chongqing University Three Gorges Hospital in Chongqing, China, from January 20 to February 3, 2020；The discharge time was from January 29 to February 11, 2020. The main results and indicators of epidemiology, demography, clinical manifestation, laboratory examination, imaging data and treatment data of 51 patients with covid-19 were collected and analyzed. The changes of blood routine and biochemical indexes at discharge and admission were compared. Compare the clinical characteristics of severe patients (including severe and critical patients) and non- severe patients (general patients). Results： Of 51 hospitalized patients with COVID-19, the median age was 45 years (interquartile range, 34-51; range, 16-68 years) and 32 (62.7%) were men.43（84.3%）patients had been to Wuhan or Other Hubei areas outside Wuhan，and 4（7.7%） patients had a clear contact history of COVID-19 patients before the onset of the disease, and 4（7.7%） patients had no clear epidemiological history of COVID-19.Common symptoms included fever (43 [84.3%]), cough (38 [74.5%]) and fatigue (22 [43.1%]). Lymphopenia was observed in 26 patients (51.0%), and elevated C-reactive protein level in 32 patients (62.7%). Ground-glass opacity was the typical radiological finding on chest computed tomography (41 [80.4%])，Local consolidation of pneumonia in some patients(17 [33.3%]).Most of the patients were treated with traditional Chinese medicine decoction (28 [54.9%])，all of them received aerosol inhalation of recombinant human interferon a-1b for injection and oral antiviral therapy with Lopinavir and Ritonavir tablets (51 [100%]); Most of the patients were given Bacillus licheniformis capsules regulated intestinal flora treatment (44 [86.3%]). 10 patients (19.6%) received short-term (3-5 days) glucocorticoid treatment. Compared with non-severe patients (n = 44), severe patients (n = 7) were older (median age, 52 years vs 44 years), had a higher proportion of diabetes mellitus (4 [57.1%] vs 0 [0.0%]), most of them needed antibiotic treatment (7 [100%] vs 4 [9.1%], most of them needed nutritional diet (6 [85.7%) vs 0 [0.0%], and were more likely to have dyspnea (6 [85.7%] vs 5 [11.4%])，most of them needed noninvasive mechanical ventilation (6 [85.7%] vs 0 [0.0%]). Except one patient died, the remaining 50 patients were discharged according to the discharge standard, the common clinical symptoms disappeared basically, the lymphocyte increased significantly (P=0.008), CRP decreased significantly (P &lt;0.001). The median length of stay was 12 days (IQR, 9-13). Conclusion：In 51 single center cases confirmed as COVID-19 and discharged from the hospital, 13.7% of the patients were severe. The main clinical symptoms of patients with COVID-19 were fever, cough and asthenia，Some patients had obvious dyspnea. They had clinical laboratory and radiologic characteristics. There is no specific drug treatment for the disease. For the treatment of COVID-19, in addition to oxygen inhalation and antiviral treatment, attention should be paid to the dialectical treatment of traditional Chinese medicine, regulation of intestinal flora, nutritional support treatment and other comprehensive treatment.</jats:p>",2020-02-23,"['liu lei', 'Gao Jian-ya']",,,,False
8d6d3be5f9353eb3358b44e646c83f1a90861b4d,medrxiv,The efficacy of convalescent plasma for the treatment of severe influenza,doi.org/10.1101/2020.02.20.20025593,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background. Administration of convalescent plasma may be of clinical benefit for treatment of severe acute viral respiratory infections. However, no clear evidence exists to support or oppose convalescent plasma use in clinical practice. We conducted a systematic review and meta-analysis to assess the evidence of randomized controlled trials (RCTs) in the convalescent plasma for the treatment of severe influenza. Methods. Healthcare databases were searched in February 2020. All records were screened against the eligibility criteria. Data extraction and risk of bias assessments were undertaken. The primary outcome was case fatality rates by influenza. Results. We identified 5 RCTs of severe influenza. The pooled analyses showed no evidence for a reduction in mortality (Odds Ratio (OR) 1.06; p = 0.87; I2 = 35%). We also found non significant reductions in days in ICU and hospital, and days on mechanical ventilation. There seemed to have a biological benefit of increasing HAI titer levels and decreasing influenza B virus loads and cytokines after convalescent plasma treatment. No serious adverse events was reported between two groups. Studies were commonly of low risk of bias with high quality.  Conclusions. Convalescent plasma appears safe but may not reduce mortality in severe influenza. This therapy should be studied within the context of a well designed clinical trial for treatment of SARS Cov 2 infection.</jats:p>",2020-02-23,"['Zhiheng Xu', 'Jianmeng Zhou', 'Yongbo Huang', 'Xuesong Liu', 'Yonghao Xu', 'Sibei Chen', 'Dongdong Liu', 'Zhimin Lin', 'Xiaoqing Liu', 'Yimin Li']",,,,True
cece6efdaa5abef341313f2dabea79585de2852f,medrxiv,Epidemiological and clinical characteristics of SARS-CoV-2 and SARS-CoV: a system review,doi.org/10.1101/2020.02.20.20025601,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background:  In this article, we summarized the early epidemiologic and clinical characteristics of SARS and COVID-19 in different countries. Aim to provide recommendations for the understanding and prevention of COVID-19.  Methods: By searching pubmed, we analyzed and compared the typical cases of SARS and COVID-19 in different countries in the early stage of the outbreak. Clinical records, laboratory results, imageological diagnosis and pathologic condition were retrospectively reviewed for these cases. This paper adopts the method of descriptive statistics and tables and graphs. Findings: Six SARS-related articles (N=337 participants) and 12 COVID-19-related articles (N=50,096 participants) were eligible for this systematic review. Fever, cough and Malaise/Fatigue were the most common symptoms in SARS and COVID-19. But in general, the clinical symptoms and signs of COVID-19 were not obvious. Compared with SARS, COVID-19 was transmitted in a more diverse way, from person to person, asymptomatic infected people and possible fecal-oral transmission, created the conditions for a large-scale spread. The mortality rates of SARS and COVID-19 were (7.7%) and (2.2%) respectively, but the overall infection rate of healthcare worker of COVID-19 (3.9%) was lower than that of SARS (40.0%). We also summarize the current reports on the pathology of COVID-19, we found that the pathological features of COVID-19 have greatly similar with SARS, which manifested as acute respiratory distress syndrome (ARDS). Interpretation: The epidemiological and clinical characteristics of SARS and COVID-19 in China are very similar, but also difference. In general, COVID-19 is transmitted in more diverse ways and is more infectious, so the early recognition of disease by healthcare worker and patient is very important. Active and effective isolation measures for suspected and close contacts are necessary.</jats:p>",2020-02-25,"['mao yaqian', 'Wei Lin', 'Junping Wen', 'Gang Chen']",,,,False
a36bfdd1c9a1666401269fb0c08a3c2922bd6812,medrxiv,"Clinical Characteristics of 24 Asymptomatic Infections with COVID-19 Screened among Close Contacts in Nanjing, China",doi.org/10.1101/2020.02.20.20025619,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers.  Methods: Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed.    Findings: None of the 24 asymptomatic cases presented any obvious symptoms before nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue and etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and five (20.8%) presented stripe shadowing in the lungs. The remaining seven (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These seven cases were younger (median age: 14.0 years; P = 0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia.  Interpretation: The asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.</jats:p>",2020-02-23,"['Zhiliang Hu', 'Ci Song', 'Chuanjun Xu', 'Guangfu Jin', 'Yaling Chen', 'Xin Xu', 'Hongxia Ma', 'Wei Chen', 'Yuan Lin', 'Yishan Zheng', 'Jianming Wang', 'zhibin hu', 'Yongxiang Yi', 'Hongbing Shen']",,,,True
f5fe758315fa09ca12dfde27938878ec4d4efa1d,medrxiv,Breadth of concomitant immune responses underpinning viral clearance and patient recovery in a non-severe case of COVID-19,doi.org/10.1101/2020.02.20.20025841,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>We report the kinetics of the immune response in relation to clinical and virological features of a patient with mild-to-moderate coronavirus disease-19 (COVID-19) requiring hospitalisation. Increased antibody-secreting cells, follicular T-helper cells, activated CD4+ and CD8+ T-cells and IgM/IgG SARS-CoV-2-binding antibodies were detected in blood, prior to symptomatic recovery. These immunological changes persisted for at least 7 days following full resolution of symptoms, indicating substantial anti-viral immunity in this non-severe COVID-19.</jats:p>",2020-02-23,"['Irani Thevarajan', 'Thi HO Nguyen', 'Marios Koutsakos', 'Julian Druce', 'Leon Caly', 'Carolien E van de Sandt', 'Xiaoxiao Jia', 'Suellen Nicholson', 'Mike Catton', 'Benjamin Cowie', 'Steven Tong', 'Sharon Lewin', 'Katherine Kedzierska']",,,,False
207dcb6e3cd43cdea91d29a15be1ee34068bd54e,medrxiv,"Estimating the Asymptomatic Proportion of 2019 Novel Coronavirus onboard the Princess Cruises Ship, 2020",doi.org/10.1101/2020.02.20.20025866,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The potential infectiousness of asymptomatic COVID-19 cases together with a substantial fraction of asymptomatic infections among all infections, have been highlighted in clinical studies. We conducted statistical modeling analysis to derive the delay-adjusted asymptomatic proportion of the positive COVID-19 infections onboard the Princess Cruises ship along with the timeline of infections. We estimated the asymptomatic proportion at 17.9% (95% CrI: 15.5%-20.2%), with most of the infections occurring before the start of the 2-week quarantine.</jats:p>",2020-02-23,"['Kenji Mizumoto', 'Katsushi Kagaya', 'Alexander Zarebski', 'Gerardo Chowell']",,,,True
bd8f57ea4aadeda075d557f566a1909d68e658c4,medrxiv,Rapid colorimetric detection of COVID-19 coronavirus using a reverse tran-scriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic plat-form: iLACO,doi.org/10.1101/2020.02.20.20025874,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The recent outbreak of a novel coronavirus SARS-CoV-2 (also known as 2019-nCoV) threatens global health, given serious cause for concern. SARS-CoV-2 is a human-to-human pathogen that caused fever, severe respiratory disease and pneumonia (known as COVID-19). By press time, more than 70,000 infected people had been confirmed worldwide. SARS-CoV-2 is very similar to the severe acute respiratory syndrome (SARS) coronavirus  broke out 17 years ago. However, it has increased transmissibility as compared with the SARS-CoV, e.g. very often infected individuals without any symptoms could still transfer the virus to others. It is thus urgent to develop a rapid, accurate and onsite diagnosis methods in order to effectively identify these early infects, treat them on time and control the disease spreading. Here we developed an isothermal LAMP based method-iLACO (isothermal LAMP based method for COVID-19) to amplify a fragment of the ORF1ab gene using 6 primers. We assured the species-specificity of iLACO by comparing the sequences of 11 related viruses by BLAST (including 7 similar coronaviruses, 2 influenza viruses and 2 normal coronaviruses). The sensitivity is comparable to Taqman based qPCR detection method, detecting synthesized RNA equivalent to 10 copies of 2019-nCoV virus. Reaction time varied from 15-40 minutes, depending on the loading of virus in the collected samples. The accuracy, simplicity and versatility of the new developed method suggests that iLACO assays can be conveniently applied with for 2019-nCoV threat control, even in those cases where specialized molecular biology equipment is not available.</jats:p>",2020-02-24,"['Lin Yu', 'Shanshan Wu', 'Xiaowen Hao', 'Xuelong Li', 'Xiyang Liu', 'Shenglong Ye', 'Heng Han', 'Xue Dong', 'Xin Li', 'Jiyao Li', 'Jianmin Liu', 'Na Liu', 'Wanzhong Zhang', 'Vicent Pelechano', 'Wei-Hua Chen', 'Xiushan Yin']",,,,True
ba3efcd6b74e55327fd7db470d824fc18943f30e,medrxiv,Evaluating the impact of international airline suspensions on the early global spread of COVID-19,doi.org/10.1101/2020.02.20.20025882,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Global airline networks play a key role in the global importation of emerging infectious diseases. Detailed information on air traffic between international airports has been demonstrated to be useful in retrospectively validating and prospectively predicting case emergence in other countries. In this paper, we use a well-established metric known as effective distance on the global air traffic data from IATA to quantify risk of emergence for different countries as a consequence of direct importation from China, and compare it against arrival times for the first 24 countries. Using this model trained on official first reports from WHO, we estimate time of arrival (ToA) for all other countries. We then incorporate data on airline suspensions to recompute the effective distance and assess the effect of such cancellations in delaying the estimated arrival time for all other countries. Finally we use the infectious disease vulnerability indices to explain some of the estimated reporting delays.</jats:p>",2020-02-23,"['Aniruddha Adiga', 'Srinivasan Venkatramanan', 'James Schlitt', 'Akhil Peddireddy', 'Allan Dickerman', 'Andrei Bura', 'Andrew Warren', 'Brian D Klahn', 'Chunhong Mao', 'Dawen Xie', 'Dustin Machi', 'Erin Raymond', 'Fanchao Meng', 'Golda Barrow', 'Henning Mortveit', 'Jiangzhuo Chen', 'Jim Walke', 'Joshua Goldstein', 'Mandy L Wilson', 'Mark Orr', 'Przemyslaw Porebski', 'Pyrros A Telionis', 'Richard Beckman', 'Stefan Hoops', 'Stephen Eubank', 'Young Yun Baek', 'Bryan Lewis', 'Madhav Marathe', 'Chris Barrett']",,,,True
9896bc65559e6406d0d3cb35e9b01b953d61959d,medrxiv,From Isolation to Coordination: How Can Telemedicine Help Combat the COVID-19 Outbreak?,doi.org/10.1101/2020.02.20.20025957,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The rapid spread of Coronavirus disease 2019 (COVID-19) presents China with a critical challenge. As normal capacity of the Chinese hospitals is exceeded, healthcare professionals struggling to manage this unprecedented crisis face the difficult question of how best to coordinate the medical resources used in highly separated locations. Responding rapidly to this crisis, the National Telemedicine Center of China (NTCC), located in Zhengzhou, Henan Province, has established the Emergency Telemedicine Consultation System (ETCS), a telemedicine-enabled outbreak alert and response network. ETCS is built upon a doctor-to-doctor (D2D) approach, in which health services can be accessed remotely through terminals across hospitals. The system architecture of ETCS comprises three major architectural layers: (1) telemedicine service platform layer, (2) telemedicine cloud layer, and (3) telemedicine service application layer. Our ETCS has demonstrated substantial benefits in terms of the effectiveness of consultations and remote patient monitoring, multidisciplinary care, and prevention education and training.</jats:p>",2020-02-23,"['Yunkai Zhai', 'Yichuan Wang', 'Minhao Zhang', 'Jody Hoffer Gittell', 'Shuai Jiang', 'Baozhan Chen', 'Fangfang Cui', 'Xianying He', 'Jie Zhao', 'Xiaojun Wang']",,,,True
ae6fc64042b050df93ebb8f8045892952f18510f,medrxiv,Assessing the impact of a symptom-based mass screening and testing intervention during a novel infectious disease outbreak: The case of COVID-19,doi.org/10.1101/2020.02.20.20025973,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>A symptom-based mass screening and testing intervention (MSTI) can identify a large fraction of infected individuals during an infectious disease outbreak. China is currently using this strategy for the COVID-19 outbreak. However, MSTI might lead to increased transmission if not properly implemented. We investigate under which conditions MSTI is beneficial.</jats:p>",2020-02-23,"['Yang Ge', 'Brian Kenneth McKay', 'Shengzhi Sun', 'Feng Zhang', 'Andreas Handel']",,,,True
eb5049e9b3185f3d1617a602b1bf8f5007c1e709,medrxiv,Generation of antibodies against COVID-19 virus for development of diagnostic tools,doi.org/10.1101/2020.02.20.20025999,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The COVID-19 China coronavirus started in Dec 2019 was challenged by the lack of accurate serological diagnostic tool for this deadly disease to quickly identify and isolate the infected patients. The generation of COVID-19-specific antibodies is essential for such tasks. Here we report that polyclonal and monoclonal antibodies were generated by immunizing animals with synthetic peptides corresponding to different areas of Nucleoprotein (N) of COVID-19. The specificities of the COVID-19 antibodies were assessed by Western Blot analysis against NPs from COVID-19, MERS and SARS. Antibodies were used for immunohistochemistry staining of the tissue sections from COVID-19 infected patient, as a potential diagnostic tool. A Sandwich ELISA kit was quickly assembled for quantitation of the virus/NP of COVID-19 concentrations in the vaccine preparations. Development of POCT is also aggressively undergoing.</jats:p>",2020-02-25,"['Maohua Li', 'Ronghua Jin', 'Ya Peng', 'Cuiyan Wang', 'Wenlin Ren', 'Fudong Lv', 'Sitao Gong', 'Feng Fang', 'Qianyun Wang', 'Jianli Li', 'Tong Shen', 'Hunter Sun', 'Lei Zhou', 'Yali Cui', 'Hao Song', 'Le Sun']",,,,False
233978852b45429db49d2aabe1c9c9bfe73b1884,medrxiv,CoVID-19 in Japan: What could happen in the future?,doi.org/10.1101/2020.02.21.20026070,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>COVID-19 has been impacting on the whole world critically and constantly Since December 2019. We have independently developed a novel statistical time delay dynamic model on the basis of the distribution models from CCDC. Based only on the numbers of confirmed cases in different regions in China, the model can clearly reveal that the containment of the epidemic highly depends on early and effective isolation. We apply the model on the epidemic in Japan and conclude that there could be a rapid outbreak in Japan if no effective quarantine measures are carried out immediately.</jats:p>",2020-02-23,"['Nian Shao', 'Hanshuang Pan', 'Xingjie Li', 'Weijia Li', 'Shufen Wang', 'Yan Xuan', 'Yue Yan', 'Yu Jiang', 'Keji Liu', 'Yu Chen', 'Boxi Xu', 'Xinyue Luo', 'Christopher Y. Shen', 'Min Zhong', 'Xiang Xu', 'Xu Chen', 'Shuai Lu', 'Guanghong Ding', 'Jin Cheng', 'Wenbin Chen']",,,,True
091a8e9a61e19e88caeb039f0e3888d111b20439,medrxiv,"Epidemiological characteristics of 1212 COVID-19 patients in Henan, China",doi.org/10.1101/2020.02.21.20026112,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Based on publicly released data for 1212 patients, we investigated the epidemiological characteristics of COVID-19 in Henan of China. The following findings are obtained: 1) COVID-19 patients in Henan show gender (55% vs 45%) and age (81% aged between 21 and 60) preferences, possible causes were explored; 2) Statistical analysis on 483 patients reveals that the estimated average, mode and median incubation periods are 7.4, 4 and 7 days; Incubation periods of 92% patients were no more than 14 days; 3) The epidemic of COVID-19 in Henan has undergone three stages and showed high correlations with the numbers of patients that recently return from Wuhan; 4) Network analysis on the aggregate outbreak phenomena of COVID-19 revealed that 208 cases were clustering infected, and various people's Hospital are the main force in treating patients. The related investigations have potential implications for the prevention and control of COVID-19.</jats:p>",2020-02-23,"['Pei Wang', 'Junan Lu', 'Yanyu Jin', 'Mengfan Zhu', 'Lingling Wang', 'Shunjie Chen']",,,,True
eaf0b485f290fa884dd18de71be79d86de20eb31,medrxiv,"Public Exposure to Live Animals, Behavioural Change, and Support in Containment Measures in response to COVID-19 Outbreak: a population-based cross sectional survey in China",doi.org/10.1101/2020.02.21.20026146,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background In response to the COVID-19 outbreak, we aimed to investigate behavioural change on exposure to live animals before and during the outbreak, and public support and confidence for governmental containment measures. Methods A population-based cross-sectional telephone survey via random dialing was conducted in Wuhan (the epicentre) and Shanghai (an affected city with imported cases) between 1 and 10 February, 2020. 510 residents in Wuhan and 501 residents in Shanghai were randomly sampled. Differences of outcome measures were compared before and during the outbreak, and between two cities. Findings  Proportion of respondents visiting wet markets at usual was 23.3% (119/510) in Wuhan and 20.4% (102/501) in Shanghai. During the outbreak, it decreased to 3.1% (16) in Wuhan (p&lt;0.001), and 4.4% (22) in Shanghai (p&lt;0.001). Proportion of those consuming wild animal products declined from 10.2% (52) to 0.6% (3) in Wuhan (p&lt;0.001), and from 5.2% (26) to 0.8% (4) in Shanghai (p&lt;0.001). 79.0% (403) of respondents in Wuhan and 66.9% (335) of respondents in Shanghai supported permanent closure of wet markets (P&lt;0.001). 95% and 92% of respondents supported banning wild animal trade and quarantining Wuhan, and 75% were confident towards containment measures. Females and the more educated were more supportive for the above containment measures. Interpretation  The public responded quickly to the outbreak, and reduced exposure to live animals, especially in Wuhan. With high public support in containment measures, better regulation of wet markets and healthy diets should be promoted.</jats:p>",2020-02-23,"['Zhiyuan Hou', 'Leesa Lin', 'Liang Lu', 'Fanxing Du', 'Mengcen Qian', 'Yuxia Liang', 'Juanjuan Zhang', 'Hongjie Yu']",,,,True
d12b31daa935e9043a9f526a2547b6216ada7cde,medrxiv,"2019 Novel Coronavirus can be detected in urine, blood, anal swabs and oropharyngeal swabs samples",doi.org/10.1101/2020.02.21.20026179,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>We tested samples collected from nine patients diagnosed with coronavirus disease 2019 (COVID-19). The virus was found in urine, blood, anal swabs and oropharyngeal swabs. It is the first time for SARS-CoV-2 found in urine, though no urinary irritation was found.</jats:p>",2020-02-25,"['Liang Peng', 'Jing Liu', 'Wenxiong Xu', 'Qiumin Luo', 'Keji Deng', 'Bingliang Lin', 'Zhiliang Gao']",,,,True
923b209c59ba069eec8640921891a26b61c0b03a,medrxiv,Comparison of throat swabs and sputum specimens for viral nucleic acid detection in 52 cases of novel coronavirus (SARS-Cov-2) infected pneumonia (COVID-19),doi.org/10.1101/2020.02.21.20026187,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Abstract Background: In December 2019, a novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19) occurred in Wuhan, China. Diagnostic test based on real-time reverse transcription polymerase chain reaction assay (qRT-PCR) was the main means of confirmation, and sample collection was mostly throat swabs, which was easy to miss the diagnosis. It is necessary to seek specimen types with higher detection efficiency and accuracy. Methods: Paired specimens of throat swabs and sputum were obtained from 54 cases, and RNA was extracted and tested for 2019-nCoV (equated with SARS-CoV-2) by qRT-PCR assay. Results: The positive rates of 2019-nCoV from sputum specimens and throat swabs were 76.9% and 44.2%, respectively. Sputum specimens showed a significantly higher positive rate than throat swabs in detecting viral nucleic acid using qRT-PCR assay (P=0.001). Conclusions: The detection rates of 2019-nCoV from sputum specimens are significantly higher than throat swabs. We suggest that sputum would benefit for the detection of 2019-nCoV in patients who produce sputum. The results can facilitate the selection of specimens and increase the accuracy of diagnosis.</jats:p>",2020-02-23,"['Chenyao Lin', 'Jie Xiang', 'Mingzhe Yan', 'Hongze Li', 'Shuang Huang', 'Changxin Shen']",,,,False
ec96ac326d77b724407145a0e7d173ae6bac4115,medrxiv,Epidemiological Development of Novel Coronavirus Pneumonia in China and Its Forecast,doi.org/10.1101/2020.02.21.20026229,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>ABSTRACT  BACKGROUND AND OBJECTIVE The novel coronavirus (SARS-Cov-2) infected coronavirus disease 2019 (COVID-19) was broken out in Wuhan and Hubei province for more than a month. It severely threats people's health of thousands in Chin and even other countries. In order to prevent its wide spread, it is necessary to understand the development of the epidemic with precise mathematical language.  METHODS    The various data of novel coronavirus pneumonia were collected from the official websites of the National Health Committee of the People's Republic of China. According to epidemic and administrative division, three groups were divided to analyze the data, Hubei Province (including Wuhan), nationwide without Hubei and Henan Province. With classic SIR models, the fitting epidemiological curves of incidence have made, and basic reproduction number (R0) was also calculated as well. Therefore the disease's infection intensity, peak time and the epidemiological end time can be deduced.</jats:p>",2020-02-26,"['Shan shan Wu', 'Pan pan Sun', 'Rui ling Li', 'Liang Zhao', 'Yan li Wang', 'Li fang Jiang', 'Jin Bo Deng']",,,,False
87b89b038b28d2ba0bcfd2203845bf15f922c1b5,medrxiv,Evolving epidemiology of novel coronavirus diseases 2019 and possible interruption of local transmission outside Hubei Province in China: a descriptive and modeling study,doi.org/10.1101/2020.02.21.20026328,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background The COVID-19 epidemic originated in Wuhan City of Hubei Province in December 2019 and has spread throughout China. Understanding the fast evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy.  Methods We collected individual information on 8,579 laboratory-confirmed cases from official publically sources reported outside Hubei in mainland China, as of February 17, 2020. We estimated the temporal variation of the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (Rt) at the provincial level.  Results   The median age of the cases was 44 years, with an increasing of cases in younger age groups and the elderly as the epidemic progressed. The delay from symptom onset to hospital admission decreased from 4.4 days (95%CI: 0.0-14.0) until January 27 to 2.6 days (0.0-9.0) from January 28 to February 17. The mean incubation period was estimated at 5.2 days (1.8-12.4) and the mean serial interval at 5.1 days (1.3-11.6). The epidemic dynamics in provinces outside Hubei was highly variable, but consistently included a mix of case importations and local transmission. We estimate that the epidemic was self-sustained for less than three weeks with Rt reaching peaks between 1.40 (1.04-1.85) in Shenzhen City of Guangdong Province and 2.17 (1.69-2.76) in Shandong Province. In all the analyzed locations (n=10) Rt was estimated to be below the epidemic threshold since the end of January.  Conclusion   Our findings suggest that the strict containment measures and movement restrictions in place may contribute to the interruption of local COVID-19 transmission outside Hubei Province. The shorter serial interval estimated here implies that transmissibility is not as high as initial estimates suggested.</jats:p>",2020-02-23,"['Juanjuan Zhang', 'Maria Litvinova', 'Wei Wang', 'Yan Wang', 'Xiaowei Deng', 'Xinghui Chen', 'Mei Li', 'Wen Zheng', 'Lan Yi', 'Xinhua Chen', 'Qianhui Wu', 'Yuxia Liang', 'Xiling Wang', 'Juan Yang', 'Kaiyuan Sun', 'Ira M. Longini', 'M. Elizabeth Halloran', 'Peng Wu', 'Benjamin J. Cowling', 'Stefano Merler', 'Cecile Viboud', 'Alessandro Vespignani', 'Marco Ajelli', 'Hongjie Yu']",,,,True
8e0481979dcd13b668686cbf3e2c8b51e5b8cf64,medrxiv,"Real-time monitoring the transmission potential of COVID-19 in Singapore, February 2020",doi.org/10.1101/2020.02.21.20026435,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The ongoing COVID-19 epidemic that spread widely in China since December 2019 is now generating local transmission in multiple countries including Singapore as of March 5, 2020. This highlights the need to monitor in real time the transmission potential of COVID-19. In Singapore, four major COVID-19 case clusters have emerged thus far. Here we estimate the effective reproduction number, Rt, of COVID-19 in Singapore from the publicly available daily case series of imported and autochthonous cases by date of symptoms onset, after adjusting the local cases for reporting delays. We also derive the reproduction number from the distribution of cluster sizes using a branching process analysis. The effective reproduction number peaked with a mean value ~1.0 around February 6-12, 2020 and declined thereafter. As of March 5, 2020, our most recent estimate of Rt is at 0.9 (95% CI: 0.7,1.0) while an estimate of the overall R based on cluster size distribution is at 0.7 (95% CI: 0.5, 1.0). The trajectory of the reproduction number in Singapore underscore the significant effects of containment efforts in Singapore while at the same time suggest the need to sustain social distancing and active case finding efforts to stomp out all active chains of transmission.</jats:p>",2020-02-25,"['Amna Tariq', 'Yiseul Lee', 'Kimberlyn Roosa', 'Seth Blumberg', 'Ping Yan', 'Stefan Ma', 'Gerardo Chowell']",,,,True
29bc34aad802ab6b35074f23c631540a84b16d0d,medrxiv,Trends in Transmissibility of 2019 Novel Coronavirus-infected Pneumonia in Wuhan and 29 Provinces in China,doi.org/10.1101/2020.02.21.20026468,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: The 2019 novel coronavirus infected pneumonia (COVID- 19) represents a significant public health threat. The COVID-19 emerged in December 2019 in Wuhan, China and rapidly spread to other regions and countries. The variation in transmission patterns and disease spread in regard to time or among different locations, partially reflecting the public health in- tervention effects, remains to be quantified. As most transmissibility-related epidemic parameters are unknown, we sought, with minimal assumptions, to estimate real-time transmissibility and forecast new cases using dynamic modelling. Method: Using the cases reported from the National Health Commission of China and transportation data, including the total number of travelling hours through railway, airplane, and car outbound from Wuhan, we have built a time-series model to estimate real-time underlying transmission rates of newly generated cases sequentially from January 20, 2020 to Feb 13, 2020 in Wuhan, Hubei province and other 28 provinces in China. We quantified the instantaneous transmission rate and relative reproduction number (R_t) of COVID-19, and evaluated whether public health intervention affected the case transmissibility in each province. Based on the current estimates, we have predicted the trend of disease spread with a high level of certainty. Findings: We estimated that R_t declined from the range of 4 to 5 towards 1 and remained below unity, while there was an initial growth followed by a decline in a shorter period in Hubei and other provinces. The ratio of transmission rates decreased dramatically from January 23 to 27 likely due to the rigorous public health intervention implemented by the government beginning on January 23, 2020. The mean duration of the infectious period was 6 to 9 days. We have predicted the trend of infection sizes which be- came stable in provinces around February 19 to 24, 2020, and the date of containment would be one-week later in Wuhan. Interpretation: Public health interventions implemented at both the so- cial and personal levels are effective in preventing outbreaks of COVID-19 in Wuhan and other provinces. Model prediction results suggested that COVID- 19 will be contained around the end of February 2020 in China. Keywords: Coronavirus, COVID-19, transmissibility, dynamic reproduction number R, statistical modelling, pneumonia outbreak</jats:p>",2020-02-25,"['Huazhen Lin', 'Wei Liu', 'Hong Gao', 'Jinyu Nie', 'Qiao Fan']",,,,True
d2e2c54ac38ef8fbd461bb7903e38c227373188c,medrxiv,"Estimating the serial interval of the novel coronavirus disease (COVID-19): A statistical analysis using the public data in Hong Kong from January 16 to February 15, 2020",doi.org/10.1101/2020.02.21.20026559,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Backgrounds: The emerging virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a large outbreak of novel coronavirus disease (COVID-19) in Wuhan, China since December 2019. Based on the publicly available surveillance data, we identified 21 transmission chains in Hong Kong and estimated the serial interval (SI) of COVID-19. Methods: Index cases were identified and reported after symptoms onset, and contact tracing was conducted to collect the data of the associated secondary cases. An interval censored likelihood framework is adopted to fit a Gamma distribution function to govern the SI of COVID-19.  Findings: Assuming a Gamma distributed model, we estimated the mean of SI at 4.4 days (95%CI: 2.9−6.7) and SD of SI at 3.0 days (95%CI: 1.8−5.8) by using the information of all 21 transmission chains in Hong Kong.  Conclusion: The SI of COVID-19 may be shorter than the preliminary estimates in previous works. Given the likelihood that SI could be shorter than the incubation period, pre-symptomatic transmission may occur, and extra efforts on timely contact tracing and quarantine are recommended in combating the COVID-19 outbreak.</jats:p>",2020-02-25,"['Shi Zhao', 'Daozhou Gao', 'Zian Zhuang', 'Marc Chong', 'Yongli Cai', 'Jinjun Ran', 'Peihua Cao', 'Kai Wang', 'Yijun Lou', 'Weiming Wang', 'Lin Yang', 'Daihai He', 'Maggie Wang']",,,,False
54d2fd5689ac3255e8041c36b5fb333a3bd3f9b2,medrxiv,A Novel Method for the Estimation of a Dynamic Effective Reproduction Number (Dynamic-R) in the CoViD-19 Outbreak,doi.org/10.1101/2020.02.22.20023267,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The CoViD-19 outbreak has escalated to a pandemic in the last few weeks, with no signs of stopping. Pharmaceutical solutions based upon virologic studies, at this point, remain inconclusive. In contrast, this paper looks towards epidemiological models during this phase of viral growth, in particular, by providing a responsive, timely model of the R value based on the previous few days' results. Such an R value, although bearing less statistical precision due to limited sampling, could allow R to become a more effective, responsive standalone measure of infectious transmission. It demonstrates that the R value can be used as a dynamic,  time-dependent indicator without the use of curve-fitting, and also estimates the most recent R-value of the CoViD-19 outbreak to be about 4.29, based on  the data from the previous 3 days.</jats:p>",2020-02-25,['Yi Chen Chong'],,,,True
4f8d24c531d2c334969e09e4b5aed66dcc925c4b,medrxiv,"Association of radiologic findings with mortality of patients infected with 2019 novel coronavirus in Wuhan, China",doi.org/10.1101/2020.02.22.20024927,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Radiologic characteristics of 2019 novel coronavirus (2019-nCoV) infected pneumonia (NCIP) which had not been fully understood are especially important for diagnosing and predicting prognosis. We retrospective studied 27 consecutive patients who were confirmed NCIP, the clinical characteristics and CT image findings were collected, and the association of radiologic findings with mortality of patients was evaluated. 27 patients included 12 men and 15 women, with median age of 60 years (IQR 47-69). 17 patients discharged in recovered condition and 10 patients died in hospital. The median age of mortality group was higher compared to survival group (68 (IQR 63-73) vs 55 (IQR 35-60), P = 0.003). The comorbidity rate in mortality group was significantly higher than in survival group (80% vs 29%, P = 0.018). The predominant CT characteristics consisted of ground glass opacity (67%), bilateral sides involved (86%), both peripheral and central distribution (74%), and lower zone involvement (96%). The median CT score of mortality group was higher compared to survival group (30 (IQR 7-13) vs 12 (IQR 11-43), P = 0.021), with more frequency of consolidation (40% vs 6%, P = 0.047) and air bronchogram (60% vs 12%, P = 0.025). An optimal cutoff value of a CT score of 24.5 had a sensitivity of 85.6% and a specificity of 84.5% for the prediction of mortality. 2019-nCoV was more likely to infect elderly people with chronic comorbidities. CT findings of NCIP were featured by predominant ground glass opacities mixed with consolidations, mainly peripheral or combined peripheral and central distributions, bilateral and lower lung zones being mostly involved. A simple CT scoring method was capable to predict mortality.</jats:p>",2020-02-23,"['Mingli Yuan', 'Wen Yin', 'Zhaowu Tao', 'Weijun Tan', 'Yi Hu']",,,,True
5a9164999237a46d3d6aed53bd59b17d91a9e6d0,medrxiv,SARS-CoV-2 transmission in cancer patients of a tertiary hospital in Wuhan,doi.org/10.1101/2020.02.22.20025320,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>In December 2019, an outbreak of atypical pneumonia known as 2019 novel coronavirus disease (COVID-19) occurred in Wuhan, China. This new type of pneumonia is characterized by rapid human-to-human transmission. Among the different disease types, cancer patients are often recalled to the hospital for treatment and disease surveillance, and the majority of cancer treatments such as chemotherapy and radiotherapy are immunosuppressive.  This prompts us to consider if cancer patients were at an elevated risk of SARS-CoV-2 infection.  A total of 1,524 cancer patients who were managed at our tertiary cancer institution-Zhongnan hospital of Wuhan University were reviewed during the period of Dec 30, 2019 to Feb 17, 2020. It was found that cancer patients had an estimated 2-fold increased risk of COVID-19 than the general population. We identified twelve patients who were infected with SARS-CoV-2, with two recorded deaths (16.7%), albeit one patient passed away from a COVID-19 unrelated cause. Interestingly, only five of these patients were ongoing treatment at the time of contracting the virus, suggesting that hospital visitation was the likely factor contributing to the elevated incidence in cancer patients. Moreover, we also observed that the incidence of severe COVID-19 was not higher than in the general population. Consequently, for cancer patients who require treatment, proper isolation protocols must be in place to mitigate the risk of SARS-CoV-2 infection.</jats:p>",2020-02-25,"['Jing Yu', 'Wen Ouyang', 'Melvin L.K. Chua', 'Conghua Xie']",,,,True
04030bba3035a58c7725ae267973206f6eb6c0b4,medrxiv,Development and Evaluation of A CRISPR-based Diagnostic For 2019-novel Coronavirus,doi.org/10.1101/2020.02.22.20025460,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: The recent outbreak of infections by the 2019 novel coronavirus (2019-nCoV), the third zoonotic CoV has raised great public health concern. The demand for rapid and accurate diagnosis of this novel pathogen brought significant clinical and technological challenges. Currently, metagenomic next-generation sequencing (mNGS) and reverse-transcription PCR (RT-PCR) are the most widely used molecular diagnostics. Methods: 2019-nCoV infections were confirmed in 52 specimens by mNGS. Genomic information was analyzed and used for the design and development of an isothermal, CRISPR-based diagnostic for this novel virus. The diagnostic performance of CRISPR-nCoV was assessed and compared across three technology platforms (mNGS, RT-PCR and CRISPR). Results: 2019-nCoVs sequenced in our study were conserved with the Wuhan strain, and shared certain genetic similarity with SARS-CoV. A high degree of variation in the level of viral RNA was observed in clinical specimens. CRISPR-nCoV demonstrated a near single-copy sensitivity and great clinical sensitivity with a shorter turn-around time than RT-PCR. Conclusion: CRISPR-nCoV presents as a promising diagnostic option for the emerging pathogen.</jats:p>",2020-02-23,"['Tieying Hou', 'Weiqi Zeng', 'Minling Yang', 'Wenjing Chen', 'Lili Ren', 'Jingwen Ai', 'Ji Wu', 'Yalong Liao', 'Xuejing Gou', 'Yongjun Li', 'Xiaorui Wang', 'Hang Su', 'Jianwei Wang', 'Bing Gu', 'Teng Xu']",,,,True
dd205866a714e372dcf465cf944c78233caadcd9,medrxiv,Temperature significant change COVID-19 Transmission in 429 cities,doi.org/10.1101/2020.02.22.20025791,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background   There is no evidence supporting that temperature changes COVID-19 transmission.  Methods We collected the cumulative number of confirmed cases of all cities and regions affected by COVID-19 in the world from January 20 to February 4, 2020, and calculated the daily means of the average, minimum and maximum temperatures in January. Then, restricted cubic spline function and generalized linear mixture model were used to analyze the relationships.   Results There were in total 24,232 confirmed cases in China and 26 overseas countries. In total, 16,480 cases (68.01%) were from Hubei Province. The lgN rose as the average temperature went up to a peak of 8.72℃ and then slowly declined. The apexes of the minimum temperature and the maximum temperature were 6.70℃ and 12.42℃ respectively. The curves shared similar shapes. Under the circumstance of lower temperature, every 1℃ increase in average, minimum and maximum temperatures led to an increase of the cumulative number of cases by 0.83, 0.82 and 0.83 respectively. In the single-factor model of the higher-temperature group, every 1℃ increase in the minimum temperature led to a decrease of the cumulative number of cases by 0.86.   Conclusion  The study found that, to certain extent, temperature could significant change COVID-19 transmission, and there might be a best temperature for the viral transmission, which may partly explain why it first broke out in Wuhan. It is suggested that countries and regions with a lower temperature in the world adopt the strictest control measures to prevent future reversal.</jats:p>",2020-02-25,"['Mao Wang', 'Aili Jiang', 'Lijuan Gong', 'Lina Luo', 'Wenbin Guo', 'Chuyi Li', 'Jing Zheng', 'Chaoyong Li', 'Bixing Yang', 'Jietong Zeng', 'Youping Chen', 'Ke Zheng', 'Hongyan Li']",,,,False
7fd337f16780aba8f1e599ce7516dc9b1d80a546,medrxiv,"Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study",doi.org/10.1101/2020.02.22.20026500,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>OBJECTIVE: To study the neurological manifestations of patients with coronavirus disease 2019 (COVID-19).  DESIGN: Retrospective case series SETTING: Three designated COVID-19 care hospitals of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China. PARTICIPANTS: Two hundred fourteen hospitalized patients with laboratory confirmed diagnosis of severe acute respiratory syndrome from coronavirus 2 (SARS-CoV-2) infection. Data were collected from 16 January 2020 to 19 February 2020. MAIN OUTCOME MEASURES: Clinical data were extracted from electronic medical records and reviewed by a trained team of physicians. Neurological symptoms fall into three categories: central nervous system (CNS) symptoms or diseases (headache, dizziness, impaired consciousness, ataxia, acute cerebrovascular disease, and epilepsy), peripheral nervous system (PNS) symptoms (hypogeusia, hyposmia, hypopsia, and neuralgia), and skeletal muscular symptoms. Data of all neurological symptoms were checked by two trained neurologists. RESULTS: Of 214 patients studied, 88 (41.1%) were severe and 126 (58.9%) were non-severe patients. Compared with non-severe patients, severe patients were older (58.7 ± 15.0 years vs 48.9 ± 14.7 years), had more underlying disorders (42 [47.7%] vs 41 [32.5%]), especially hypertension (32 [36.4%] vs 19 [15.1%]), and showed less typical symptoms such as fever (40 [45.5%] vs 92 [73%]) and cough (30 [34.1%] vs 77 [61.1%]). Seventy-eight (36.4%) patients had neurologic manifestations. More severe patients were likely to have neurologic symptoms (40 [45.5%] vs 38 [30.2%]), such as acute cerebrovascular diseases (5 [5.7%] vs 1 [0.8%]), impaired consciousness (13 [14.8%] vs 3 [2.4%]) and skeletal muscle injury (17 [19.3%] vs 6 [4.8%]). CONCLUSION: Compared with non-severe patients with COVID-19, severe patients commonly had neurologic symptoms manifested as acute cerebrovascular diseases, consciousness impairment and skeletal muscle symptoms.</jats:p>",2020-02-25,"['Ling Mao', 'Mengdie Wang', 'Shanghai Chen', 'Quanwei He', 'Jiang Chang', 'Candong Hong', 'Yifan Zhou', 'David Wang', 'Yanan Li', 'Huijuan Jin', 'Bo Hu']",,,,True
379ea88c17d8734504b5b7e3c4454e5efc2a90fc,medrxiv,A Peptide-based Magnetic Chemiluminescence Enzyme Immunoassay for Serological Diagnosis of Corona Virus Disease 2019 (COVID-19),doi.org/10.1101/2020.02.22.20026617,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>A respiratory illness has been spreading rapidly in China, since its outbreak in Wuhan city, Hubei province in December 2019. The illness was caused by a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical manifestations related to SARS-CoV-2 infection ranged from no symptom to fatal pneumonia. World Health Organization (WHO) named the diseases associated with SARS-CoV-2 infection as COVID-19. Real time RT-PCR is the only laboratory test available till now to confirm the infection. However, the accuracy of real time RT-PCR depends on many factors, including sampling location and of methods, quality of RNA extraction and training of operators etc. Variations in these factors might significantly lower the sensitivity of the detection. We developed a peptide-based luminescent immunoassay to detect IgG and IgM. Cut-off value of this assay was determined by the detection of 200 healthy sera and 167 sera from patients infected with other pathogens than SARS-CoV-2. To evaluate the performance of this assay, we detected IgG and IgM in the 276 sera from confirmed patients. The positive rate of IgG and IgM were 71.4% (197/276) and 57.2% (158/276) respectively. By combining with real time RT-PCR detection, this assay might help to enhance the accuracy of diagnosis of SARS-CoV-2 infection.</jats:p>",2020-02-25,"['Xuefei Cai', 'Juan Chen', 'Jieli Hu', 'Quanxin Long', 'Haijun Deng', 'Kai Fan', 'Pu Liao', 'Beizhong Liu', 'Guicheng Wu', 'Yaokai Chen', 'Zhijie Li', 'Kun Wang', 'Xiaoli Zhang', 'Wenguang Tian', 'Jianglin Xiang', 'Hongxin Du', 'Jing Wang', 'Yuan Hu', 'Ni Tang', 'Yong Lin', 'Jihua Ren', 'Luyi Huang', 'Jie Wei', 'Chunyang Gan', 'Yanmeng Chen', 'Qingzhu Gao', 'Amei Chen', 'Changlong He', 'Daoxin Wang', 'Peng Hu', 'Fachun Zhou', 'Ailong Huang', 'Ping Liu', 'Deqiang Wang']",,,,False
eeae21c913759e8cf4c345e561457fe7ef84480f,medrxiv,Applying chemical reaction transition theory to predict the latent transmission dynamics of coronavirus outbreak in China,doi.org/10.1101/2020.02.22.20026815,,,See https://www.medrxiv.org/submit-a-manuscript,<jats:p>The recent outbreak of the Covid-19 suggests a rather long latent phase that precludes public health officials to predict the pandemic transmission on time. Here we apply mass action laws and chemical transition theory to propose a kinetic model that accounts for viral transmission dynamics at the latent phase. This model is useful for authorities to make early preventions and control measurements that stop the spread of a deadly new virus.</jats:p>,2020-02-25,['Peng Xu'],,,,True
8b2e50eb3ea84225580fbdbccccb4fcd3f062feb,medrxiv,"Intrinsic growth rules of patients infected, dead and cured with 2019 novel coronavirus in mainland China",doi.org/10.1101/2020.02.23.20024802,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background An outbreak of a novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) was first occurred in Wuhan, China, in December 2019 and then spread rapidly to other regions. It has been declared that at least one confirmed case infected by SARS-CoV-2 was found in each province of China by late January 2020. Methods We collected the time series data of the cumulative number of confirmed infected, dead, and cured cases from the health commissions in 31 provinces in mainland China. A simple descriptive model in a logistic form was formulated to infer the intrinsic epidemic rules of COVID-19. Furthermore, we compared the intrinsic epidemic rules of COVID-19 in Hubei with that of the severe acute respiratory syndrome (SARS) in Beijing, which was obtained from the Ministry of Public Health of China in 2003.  Results The feature of data of three population groups in all the provinces could be well captured (R-square&gt;0.95) by the proposed descriptive model with slight variation among different provinces. By comparing fitted parameters, we found that the fitted curve of the infected case is the earliest to be saturated and has the lowest semi-saturation period in both COVID-19 and SARS. While all three population groups of SARS are later to saturate and have a longer semi-saturation period than that of COVID-19. Conclusions Our model is robust and stable to depict the intrinsic growth rule for the cumulative number of confirmed infected, dead, and cured cases in 30 provinces, which could depict the epidemic situation in mainland China very well. Despite the virus caused SARS (SARS-CoV) and the virus caused COVID-19 (SARS-CoV-2) are homologous, their epidemiologic characteristics are quite different. The duration of the outbreak would be shorter for COVID-19.</jats:p>",2020-02-25,"['Chuanliang Han', 'Yimeng Liu', 'Saini Yang']",,,,True
18c37bae525b1a11c9c108e6eda84e14ebd84e4b,medrxiv,"Conjunctival polymerase chain reaction-tests of 2019 novel coronavirus in patients in Shenyang,China",doi.org/10.1101/2020.02.23.20024935,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Purpose: The 2019 novel coronavirus(COVID-19) mainly transmitted by person-to-person through inhalation of respiratory droplets. We report the laboratory results of conjunctival PCR-tests and some clinical features of these patients in shenyang China. Design: This is a cross-sectional non-randomized study. Subjects: The study include 14 confirmly diagnosed cases, 16 suspected cases and some medical observed patients. Methods:  All patients with diagnosed and suspected COVID-19 were admitted to a designated hospital in Shenyang,China. We  collected  conjunctival samples of these patients to do the laboratory tests by real time RT-PCR.Medical observed patients were enrolled if they had clinical symptoms. Then we analysed the PCR results and clinical data from eletronic medical records in order to find some relationships. Main Outcome Measures: Clinical condition and PCR results of conjunctival swabs compared with other specimens. Results: One of the identified case coverted from suspected case without typical clinical symptoms. Twenty-two medical observed cases  were removed because none of them converted to identified cases.One of the suspected converted to identified case recently.The included cases in our study are imported cases with less underlying diseases and the severity of their infection was relatively moderate. All the conjunctival results of PCR-test were negative. Two cases had typical clinical symptoms but were finally confirmed by repeated pharynx swab tests. Conclusion: Conjunctiva may be a transmission way of COVID-19. And ocular conjunctival swabs in combination with PCR test could be a non-invasive,convenient and feasible diagnostic method for identifying the infection of COVID-19. Emphasis on the false-negative results is vital.</jats:p>",2020-02-25,"['li Xu', 'Xinyue Zhang', 'Wei Song', 'Baijun Sun', 'Jinping Mu', 'Xue Dong', 'Bing Wang']",,,,False
bbba5ff9ab9eccef99a0bbc6ea557a373158bbcd,medrxiv,The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing,doi.org/10.1101/2020.02.23.20026690,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The novel coronavirus SARS-CoV-2, etiological agent of recently named Coronavirus infected disease (COVID-19) by WHO, has caused more than 2, 000 deaths worldwide since its emergency in Wuhan City, Hubei province, China, in December, 2019. The symptoms of COVID-19 varied from modest, mild to acute respiratory distress syndrome (ARDS), and the latter of which is generally associated with deregulated immune cytokine production; however, we currently know little as to the interplay between the extent of clinical symptoms and the compositions of lung immune microenvironment. Here, we comprehensively characterized the lung immune microenvironment with the bronchoalveolar lavage fluid (BALF) from 3 severe and 3 mild COVID-19 patients and 8 previously reported healthy lung controls through single-cell RNA sequence (scRNA-seq) combined with TCR-seq. Our data shows that monocyte-derived FCN1+ macrophages, whereas notFABP4+ alveolar macrophages that represent a predominant macrophage subset in BALF from patients with mild diseases, overwhelm in the severely damaged lungs from patients with ARDS. These cells are highly inflammatory and enormous chemokine producers implicated in cytokine storm. Furthermore, the formation of tissue resident, highly expanded clonal CD8+ T cells in the lung microenvironment of mild symptom patients suggests a robust adaptive immune response connected to a better control of COVID-19. This study first reported the cellular atlas of lung bronchoalveolar immune microenvironment in COVID-19 patients at the single-cell resolution, and unveiled the potential immune mechanisms underlying disease progression and protection in COVID-19.</jats:p>",2020-02-26,"['Minfeng Liao', 'Yang Liu', 'Jin Yuan', 'Yanling Wen', 'Gang Xu', 'Juanjuan Zhao', 'Lin Chen', 'Jinxiu Li', 'Xin Wang', 'Fuxiang Wang', 'Lei Liu', 'Shuye Zhang', 'Zheng Zhang']",,,,True
a9c58042555c0d56b8e94bc5558db0c3dd697dcc,medrxiv,"Epidemiologic and Clinical Characteristics of 91 Hospitalized Patients with COVID-19 in Zhejiang, China: A retrospective, multi-centre case series",doi.org/10.1101/2020.02.23.20026856,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background Recent studies have focused initial clinical and Epidemiologic characteristics on the COVID-19, mainly revealing situation in Wuhan, Hubei.  Aim To reveal more data on the epidemiologic and clinical characteristics of COVID-19 patients outside of Wuhan, in Zhejiang, China.  Design  Retrospective case series.  Methods 88 cases of laboratory-confirmed and 3 cases of clinical-confirmed COVID-19 were admitted to five hospitals in Zhejiang province, China. Data were collected from 20 January 2020 to 11 February 2020.  Results  Of all 91 patients, 88 (96.70%) were laboratory-confirmed COVID-19 with throat swab samples that tested positive for SARS-Cov-2 while 3 (3.30%) were clinical-diagnosed COVID-19 cases. The median age of the patients was 50 (36.5-57) years, and female accounted for 59.34%. In this sample 40 (43.96%) patients had contracted the diseases from local cases, 31 (34.07%) patients had been to Wuhan/Hubei, 8 (8.79%) cases had contacted with people from Wuhan, 11 (12.09%) cases were confirmed aircraft transmission. In particular within the city of Ningbo, 60.52% cases can be traced back to an event held in a temple. The most common symptoms were fever (71.43%), cough (60.44%) and fatigue (43.96%). The median of incubation period was 6 (IQR, 3-8) days and the median time from first visit to a doctor to confirmed diagnosis was 1 (1-2) days. According to the Chest computed tomography scans, 67.03% cases had bilateral pneumonia.  Conclusions Social activity cluster, family cluster and travel by airplane were how COVID-19 patients get transmitted and could be rapidly diagnosed COVID-19 in Zhejiang.</jats:p>",2020-02-25,"['Guo-Qing Qian', 'Nai-Bin Yang', 'Feng Ding', 'Ada Hoi Yan Ma', 'Zong-Yi Wang', 'Yue-Fei Shen', 'Chun-Wei Shi', 'Xiang Lian', 'Jin-Guo Chu', 'Lei Chen', 'Zhi-Yu Wang', 'Da-Wei Ren', 'Guo-Xiang Li', 'Xue-Qin Chen', 'Hua-Jiang Shen', 'Xiao-Min Chen']",,,,True
bf39a81c9aab9e0569f33d93d5e203d320dac024,medrxiv,Gender differences in patients with COVID-19: Focus on severity and mortality,doi.org/10.1101/2020.02.23.20026864,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Importance: The recent outbreak of Novel Coronavirus (SARS-CoV-2) Disease (COVID-19) has put the world on alert, that is reminiscent of the SARS outbreak seventeen years ago.  Objective: We aim to compare the severity and mortality between male and female patients with both COVID-19 and SARS, to explore the most useful prognostic factors for individualized assessment. Design, Setting, and Participants: We extracted the data from a case series of 43 hospitalized patients we treated, a public data set of the first 37 cases died of COVID-19 in Wuhan city and 1019 survived patients from six cities in China. We also analyzed the data of 524 patients with SARS, including 139 deaths, from Beijing city in early 2003. Main Outcomes and Measures: Severity and mortality. Results: Older age and high number of comorbidities were associated with higher severity and mortality in patients with both COVID-19 and SARS. The percentages of older age (≥65 years) were much higher in the deceased group than in the survived group in patients with both COVID-19 (83.8 vs. 13.2, P&lt;0.001) and SARS (37.4 vs. 4.9, P&lt;0.001). In the case series, men tend to be more serious than women (P=0.035), although age was comparable between men and women. In the public data set, age was also comparable between men and women in the deceased group or the survived group in patients with COVID-19. Meanwhile, gender distribution was exactly symmetrical in the 1019 survivors of COVID-19. However, the percentage of male were higher in the deceased group than in the survived group (70.3 vs. 50.0, P=0.015). The gender role in mortality was also observed in SARS patients. Survival analysis showed that men (hazard ratio [95% CI] 1.47 [1.05-2.06, P= 0.025) had a significantly higher mortality rate than women in patients with SARS. Conclusions and Relevance: Older age and male gender are risk factors for worse outcome in patients with COVID. While men and women have the same susceptibility to both SARS-CoV-2 and SARS-CoV, men may be more prone to have higher severity and mortality independent of age and susceptibility.</jats:p>",2020-02-25,"['Jian-Min Jin', 'Peng Bai', 'Wei He', 'Fei Wu', 'Xiao-Fang Liu', 'De-Min Han', 'Shi Liu', 'Jin-Kui Yang']",,,,True
efecd1130da457c2a031099292f14fc2c7964721,medrxiv,Mental health status and coping strategy of medical workers in China during The COVID-19 outbreak,doi.org/10.1101/2020.02.23.20026872,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The authors have withdrawn their manuscript whilst they perform additional experiments to test some of their conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.</jats:p>",2020-02-25,"['Chen Siyu', 'Min Xia', 'Weiping Wen', 'Liqian Cui', 'Weiqiang Yang', 'Shaokun Liu', 'Jiahua Fan Fan', 'Huijun Yue', 'Shangqing Tang', 'Bingjie Tang', 'Xiaoling Li', 'Lin Chen', 'Zili Qin', 'Kexing Lv', 'Xueqin Guo', 'Yu Lin', 'Yihui Wen', 'Wenxiang Gao', 'Ying Zheng', 'Wei Xu', 'Yun Li', 'Yang Xu', 'Li Ling', 'Wenbin Lei']",,,,False
6bdd6867205d9b09f833f01c65f1bbfdae469164,medrxiv,Deep learning Enables Accurate Diagnosis of Novel Coronavirus (COVID-19) with CT images,doi.org/10.1101/2020.02.23.20026930,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background A novel coronavirus (COVID-19) has emerged recently as an acute respiratory syndrome. The outbreak was originally reported in Wuhan, China, but has subsequently been spread world-widely. As the COVID-19 continues to spread rapidly across the world, computed tomography (CT) has become essentially important for fast diagnoses. Thus, it is urgent to develop an accurate computer-aided method to assist clinicians to identify COVID-19-infected patients by CT images.     Materials and Methods We collected chest CT scans of 88 patients diagnosed with the COVID-19 from hospitals of two provinces in China, 101 patients infected with bacteria pneumonia, and 86 healthy persons for comparison and modeling. Based on the collected dataset, a deep learning-based CT diagnosis system (DeepPneumonia) was developed to identify patients with COVID-19.  Results The experimental results showed that our model can accurately identify the COVID-19 patients from others with an excellent AUC of 0.99 and recall (sensitivity) of 0.93. In addition, our model was capable of discriminating the COVID-19 infected patients and bacteria pneumonia-infected patients with an AUC of 0.95, recall (sensitivity) of 0.96. Moreover, our model could localize the main lesion features, especially the ground-glass opacity (GGO) that is of great help to assist doctors in diagnosis. The diagnosis for a patient could be finished in 30 seconds, and the implementation on Tianhe-2 supercompueter enables a parallel executions of thousands of tasks simultaneously. An online server is available for online diagnoses with CT images by http://biomed.nscc-gz.cn/server/Ncov2019.  Conclusions The established models can achieve a rapid and accurate identification of COVID-19 in human samples, thereby allowing identification of patients.</jats:p>",2020-02-25,"['Ying Song', 'Shuangjia Zheng', 'Liang Li', 'Xiang Zhang', 'Xiaodong Zhang', 'Ziwang Huang', 'Jianwen Chen', 'Huiying Zhao', 'Yusheng Jie', 'Ruixuan Wang', 'Yutian Chong', 'Jun Shen', 'Yunfei Zha', 'Yuedong Yang']",,,,True
e4701bdf5d414ea8ca38a4d8d3f69540805293b0,medrxiv,"Clinical features and laboratory inspection of novel coronavirus pneumonia (COVID-19) in Xiangyang, Hubei",doi.org/10.1101/2020.02.23.20026963,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Since December 2019, a novel coronavirus pneumonia (COVID-19) rapidly spread in China, reached multiple continents currently.We aimed to reveal the infectious characteristics of COVID-19 that provide more information for the research of novel coronavirus. Methods: We performed a retrospective study on the clinical characteristics of 128 COVID-19 cases with laboratory-confirmed from Xiangyang No 1 Hospitalad during January 2020 to 16 February 2020. Results: Female patients account for 53.1%. The aged below 20 years that accounts for 1.6% of overall patients. The aged in 21~50, 51~65, over 66 years were accounts for 44.5%, 35.1%,18.8%, respectively. In the difference age spectrum, all severe groups compared with non-severe groups were difference significantly ( P &lt; 0.01 ). Fever ( 89.8% ) and Cough ( 67.2% ) were common clinical symptoms. The rate of patients with sore throats (14.1%) was rare. The rate of chest computed tomography scan showing ground glass opacity in overall, non-severe, severe groups were 63.3%, 60.7%, 76.2%, respectively. White blood cell counts in the normal range of overall patients, but severe group patients were increased significantly ( P &lt; 0.01). Lymphocytes of overall patients were decreased. Alanine transaminase (ALT) and aspartate transaminase (AST) in the normal range of overall patients, but its were elevated in the severe group. Creatinine (CR) and blood urea nitrogen (BUN) of overall patients in the normal range. C-reactive protein (CRP) level of all patients were increased markedly, but it in the severe group was significantly higher than that in the non-severe group ( P &lt; 0.01 ). Conclusions: Our data provide more information that advanced age, lower lymphocytes levels at the diagnosed COVID-19 patients may be a risk factor for unfavourable prognosis. The white blood cells and C-reactive protein level elevated in severe COVID-19 patients may be accompanying bacterial infection. 2019-nCov may be carries a risk factor of impaired liver and kidney function.</jats:p>",2020-02-25,['Weiliang Cao'],,,,True
1d882d90109fb4496088342cf2bcaa4fec40cf9f,medrxiv,Inferring transmission trees to guide targeting of interventions against visceral leishmaniasis and post-kala-azar dermal leishmaniasis,doi.org/10.1101/2020.02.24.20023325,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Understanding of spatiotemporal transmission of infectious diseases has improved significantly in recent years. Advances in Bayesian inference methods for individual-level geo-located epidemiological data have enabled reconstruction of transmission trees and quantification of disease spread in space and time, while accounting for uncertainty in missing data. However, these methods have rarely been applied to endemic diseases or ones in which asymptomatic infection plays a role, for which novel estimation methods are required. Here, we develop such methods to analyse longitudinal incidence data on visceral leishmaniasis (VL), and its sequela, post-kala-azar dermal leishmaniasis (PKDL), in a highly endemic community in Bangladesh. Incorporating recent data on infectiousness of VL and PKDL, we show that while VL cases drive transmission when incidence is high, the contribution of PKDL increases significantly as VL incidence declines (reaching 55% in this setting). Transmission is highly focal: &gt;85% of mean distances from inferred infectors to their secondary VL cases were &lt;300m, and estimated average times from infector onset to secondary case infection were &lt;4 months for 90% of VL infectors, but up to 2.75yrs for PKDL infectors. Estimated numbers of secondary VL cases per VL and PKDL case varied from 0-6 and were strongly correlated with the infector's duration of symptoms. Counterfactual simulations suggest that prevention of PKDL could have reduced VL incidence by up to a quarter. These results highlight the need for prompt detection and treatment of PKDL to achieve VL elimination in the Indian subcontinent and provide quantitative estimates to guide spatiotemporally-targeted interventions against VL.</jats:p>",2020-02-25,"['Lloyd A. C. Chapman', 'Simon E. F. Spencer', 'Timothy M. Pollington', 'Chris P. Jewell', 'Dinesh Mondal', 'Jorge Alvar', 'T. Deirdre Hollingsworth', 'Mary M. Cameron', 'Caryn Bern', 'Graham F. Medley']",,,,True
01d162d7fae6aaba8e6e60e563ef4c2fca7b0e18,medrxiv,"TWIRLS, an automated topic-wise inference method based on massive literature, suggests a possible mechanism via ACE2 for the pathological changes in the human host after coronavirus infection",doi.org/10.1101/2020.02.24.20025437,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Faced with the current large-scale public health emergency, collecting, sorting, and analyzing biomedical information related to the ""coronavirus"" should be done as quickly as possible to gain a global perspective, which is a basic requirement for strengthening epidemic control capacity. However, for human researchers studying the viruses and the hosts, the vast amount of information available cannot be processed effectively and in a timely manner, particularly when the scientific understanding may be limited, which can further lower the information processing efficiency. We present TWIRLS, a method that can automatically acquire, organize, and classify information. Additionally, independent functional data sources can be added to build an inference system using a machine-based approach, which can provide relevant knowledge to help human researchers quickly establish subject cognition and to make more effective decisions. TWIRLS can automatically analyze more than three million words in more than 14,000 literature articles in only 4 hours. Combining with generalized gene interaction databases creates a data interface that can help researchers to further analyze the information. Using the TWIRLS system, we found that an important regulatory factor angiotensin-converting enzyme 2 (ACE2) may be involved in the host pathological changes on binding to the coronavirus after infection. After triggering functional changes in ACE2/AT2R, an imbalance in the steady-state cytokine regulatory axis involving the Renin-Angiotensin System and IP-10 leads to a cytokine storm.</jats:p>",2020-02-26,"['Xiaoyang Ji', 'Chunming Zhang', 'Yubo Zhai', 'Zhonghai Zhang', 'Yiqing Xue', 'Chunli Zhang', 'Guangming Tan', 'Gang Niu']",,,,True
47f65bff75b7752a38ccbb540fbd74955b3addea,medrxiv,Demonstration of four entities of appendicitis in China through studying cluster/outbreak,doi.org/10.1101/2020.02.24.20026021,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: To differentiate different entities of appendicitis through studying cluster/outbreak, ascertain common setting of cluster/outbreak, and provide the epidemiological evidences of infectious etiology of appendicitis. Background: Differential diagnosis and management for perforated appendicitis and non-perforated appendicitis and the infectious etiology of appendicitis are current hot topics. Methods: Field investigation for Tibetan students were carried out and reports published in English and Chinese medical journals were reviewed.  Results: The literature review included 473 patients in 7 cluster/outbreaks of appendicitis in 6 provinces and autonomous regions. All the clusters/outbreaks occurred in group living units. We found two classic entities of appendicitis with natural history from non perforated appendicitis to perforated appendicitis and two entities of non-perforated appendicitis . In classic entities, one may represent majority of sporadic patients and the other may represent partial sporadic patients with obvious gastrointestinal manifestation. In entities of non-perforated appendicitis, one was identical to features of sporadic non-perforated appendicitis and the other one is identical to the following Tibetan students and associated with Fusobacterium. The field investigation for 120 Tibetan students with appendicitis showed that the resected appendices exhibited diffuse or focal hemorrhages and infiltration by eosinophils and by lymphocytes. Most patients had normal body temperature,  white blood cell count and neutrophil count. This is a new entity of appendicitis. The clusters/outbreaks of appendicitis showed the features of infectious disease in epidemiology. The entity of perforated appendicitis was not found. Conclusion: Studying cluster/outbreak is a good method to differentiate different entities of appendicitis and infectious etiology.</jats:p>",2020-02-26,"['Yi-Tian Guo', 'De-qiang Ye', 'Gui-fang Yang', 'Guo-zhen Liu', 'Xiao-chen Cui', 'Shi-Yun Tan', 'Yi Guo']",,,,True
99a46ba28f5811c112876ec77f570d6c10778db6,medrxiv,"WeChat, a Chinese social media, may early detect the SARS-CoV-2 outbreak in 2019",doi.org/10.1101/2020.02.24.20026682,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>We plotted daily data on the frequencies of keywords related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from WeChat, a Chinese social media. Using 'Feidian', Chinese abbreviation for SARS, may detect the SARS-CoV-2 outbreak in 2019 two weeks earlier. WeChat offered a new approach to early detect disease outbreaks.</jats:p>",2020-02-26,"['Wenjun Wang', 'Yikai Wang', 'Xin Zhang', 'Yaping Li', 'Xiaoli Jia', 'Shuangsuo Dang']",,,,True
0fd300aefb704c20f32152b97b6194015f1c74e7,medrxiv,Characterizing the transmission and identifying the control strategy for COVID-19 through epidemiological modeling,doi.org/10.1101/2020.02.24.20026773,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The outbreak of the novel coronavirus disease, COVID-19, originating from Wuhan, China in early December, has infected more than 70,000 people in China and other countries and has caused more than 2,000 deaths. As the disease continues to spread, the biomedical society urgently began identifying effective approaches to prevent further outbreaks. Through rigorous epidemiological analysis, we characterized the fast transmission of COVID-19 with a basic reproductive number 5.6 and proved a sole zoonotic source to originate in Wuhan. No changes in transmission have been noted across generations. By evaluating different control strategies through predictive modeling and Monte carlo simulations, a comprehensive quarantine in hospitals and quarantine stations has been found to be the most effective approach. Government action to immediately enforce this quarantine is highly recommended.</jats:p>",2020-02-25,"['Ke K. Zhang', 'Linglin Xie', 'Lauren Lawless', 'Huijuan Zhou', 'Guannan Gao', 'Chengbin Xue']",,,,True
5b1a2b3207e3f674b94f6f271b92c29f3a8a6754,medrxiv,Clinical and radiographic features of cardiac injury in patients with 2019 novel coronavirus pneumonia,doi.org/10.1101/2020.02.24.20027052,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: To investigate the correlation between clinical characteristics and cardiac injury of COVID-2019 pneumonia.  Methods: In this retrospective, single-center study, 41 consecutive corona virus disease 2019 (COVID-2019) patients (including 2 deaths) of COVID-2019 in Beijing Youan Hospital, China Jan 21 to Feb 03, 2020, were involved in this study. The high risk factors of cardiac injury in different COVID-2019 patients were analyzed. Computed tomographic (CT) imaging of epicardial adipose tissue (EAT) has been used to demonstrate the cardiac inflammation of COVID-2019. Results：Of the 41 COVID-2019 patients, 2 (4.88%), 32 (78.05%), 4 (9.75%) and 3 (7.32%) patients were clinically diagnosed as light, mild, severe and critical cases, according to the 6th guidance issued by the National Health Commission of China. 10 (24.4%) patients had underlying complications, such as hypertension, CAD, type 2 diabetes mellites and tumor. The peak value of TnI in critical patients is 40-fold more than normal value. 2 patients in the critical group had the onset of atrial fibrillation, and the peak heart rates reached up to 160 bpm. CT scan showed low EAT density in severe and critical patients.  Conclusion: Our results indicated that cardiac injury of COVID-2019 was rare in light and mild patients, while common in severe and critical patients. Therefore, the monitoring of the heart functions of COVID-2019 patients and applying potential interventions for those with abnormal cardiac injury related characteristics, is vital to prevent the fatality.</jats:p>",2020-02-27,"['Hui Hui', 'Yingqian Zhang', 'Xin Yang', 'Xi Wang', 'Bingxi He', 'Li Li', 'Hongjun Li', 'Jie Tian', 'Yundai Chen']",,,,True
d9eeeb81d17be6a722b11081f13576de197d249f,medrxiv,"2019 novel coronavirus disease in hemodialysis (HD) patients: Report from one HD center in Wuhan, China",doi.org/10.1101/2020.02.24.20027201,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The outbreak of COVID-19 originated in Wuhan has become a global epidemic of contagious diseases, which poses a serious threat to human life and health, especially for those with underlined diseases. However, Impacts of COVID-19 epidemic on HD center and HD patients are still unknown. In this report, we reviewed the whole course of the epidemic emerged in the HD center of Renmin Hospital, Wuhan University from January 14, 2020, the day the first case was confirmed, to February 17, 2020, the day the epidemic extinction. There are totally 37 cases among 230 HD patients and 4 cases among 33 staff being diagnosed with COVID-19. The epidemiology, clinical presentation and immune profile of dialysis patients contracted COVID-19 were further studied. We found that the two key measures we took in response to the epidemic, one was upgrading level of prevention and protection on January 21 and the other one starting universal screening, isolating, and distributing the infected cases on February 4, were effective in the epidemic control. No new COVID-19 case had been diagnosed since February 13. During the epidemic, 7 HD patients died, including 6 with COVID-19 and 1 without COVID-19. The presumed causes of death were not directly related to pneumonia, but due to cardiovascular and cerebrovascular diseases, hyperkalemia, etc. Most of the leukocytes in the peripheral blood of the HD patients infected with COVID-19 decreased, and the CT images of the chest mostly showed the ground glass like changes on the right side. The symptoms of most of the patients were mild, and there were no cases admitted to ICU. The frequency of lymphocytes in PBMCs and the serum level of inflammatory cytokines were assessed in HD patients contracted COVID-19 or not, non-HD COVID-19 patients, as well as healthy volunteers. The results showed that lymphocytes of  T cell, Th cells, killer T cells, as well as NK cells in PBMCs of HD patients decreased significantly than other groups. HD patients with COVID-19 also displayed remarkable lower serum level of inflammatory cytokines than other COVID-19 patients. Our study indicates that HD patients are the highly susceptible population and HD centers are high risk area in the outbreak of COVID-19 epidemic. Measures of prevention, protection, screening, isolation, and distribution are essential in the epidemic management and should be taken in the early stage. HD Patients with COVID-19 are mostly clinical mild and unlikely progress to severe pneumonia due to the impaired cellular immune function and incapability of mounting cytokines storm. More attention should be paid to prevent cardiovascular events, which may be the collateral impacts of COVID-19 epidemic on HD patients.</jats:p>",2020-02-25,"['Yiqiong Ma', 'Bo Diao', 'Xifeng Lv', 'Jili Zhu', 'Wei Liang', 'Lei Liu', 'Wenduo Bu', 'Huiling Cheng', 'Sihao Zhang', 'Lianhua Yang', 'Ming Shi', 'Guohua Ding', 'Bo Shen', 'Huiming Wang']",,,,True
6f53b9dff58818839c45410d11b58f0f3e327d8a,medrxiv,Estimation of risk factors for COVID-19 mortality - preliminary results,doi.org/10.1101/2020.02.24.20027268,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Since late December 2019 a new epidemic outbreak has emerged from Whuhan, China. Rapidly the new coronavirus has spread worldwide. China CDC has reported results of a descriptive exploratory analysis of all cases diagnosed until the 11th February 2020, presenting the epidemiologic curves and geo-temporal spread of COVID-19 along with case fatality rate according to some baseline characteristics, such as age, gender and several well-established high prevalence comorbidities. Despite this, we intend to increase even further the predictive value of that manuscript by presenting the odds ratio for mortality due to COVID-19 adjusted for the presence of those comorbidities and baseline characteristics such as age and gender.  Besides, we present a way to determine the risk of each particular patient, given his characteristics. We found that age is the variable that presents higher risk of COVID-19 mortality, where 60 or older patients have an OR = 18.8161 (CI95%[7.1997; 41.5517]). Regarding comorbidities, cardiovascular disease appears to be the riskiest (OR=12.8328 CI95%[10.2736; 15.8643], along with chronic respiratory disease (OR=7.7925 CI95%[5.5446; 10.4319]). Males are more likely to die from COVID-19 (OR=1.8518 (CI95%[1.5996; 2.1270]). Some limitations such as the lack of information about the correct prevalence of gender per age or about comorbidities per age and gender or the assumption of independence between risk factors are expected to have a small impact on results. A final point of paramount importance is that the equation presented here can be used to determine the probability of dying from COVID-19 for a particular patient, given its age interval, gender and comorbidities associated.</jats:p>",2020-02-25,"['Francisco Caramelo', 'Nuno Ferreira', 'Barbara Oliveiros']",,,,True
53326420d7eb607538a248c0da27d3b092f651e2,medrxiv,"Lessons learnt from 288 COVID-19 international cases: importations over time, effect of interventions, underdetection of imported cases",doi.org/10.1101/2020.02.24.20027326,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>288 cases have been confirmed out of China from January 3 to February 13, 2020. We collected and synthesized all available information on these cases from official sources and media. We analyzed importations that were successfully isolated and those leading to onward transmission. We modeled their number over time, in relation to the origin of travel (Hubei province, other Chinese provinces, other countries) and interventions. We characterized importations timeline to assess the rapidity of isolation, and epidemiologically linked clusters to estimate the rate of detection.  We found a rapid exponential growth of importations from Hubei, combined with a slower growth from the other areas. We predicted a rebound of importations from South East Asia in the upcoming weeks. Time from travel to detection has considerably decreased since the first importation, however 6 cases out of 10 were estimated to go undetected. Countries outside China should be prepared for the possible emergence of several undetected clusters of chains of local transmissions.</jats:p>",2020-02-25,"['Francesco Pinotti', 'Laura Di Domenico', 'Ernesto Ortega', 'Marco Mancastroppa', 'Giulia Pullano', 'Eugenio Valdano', 'Pierre-Yves Boelle', 'Chiara Poletto', 'Vittoria Colizza']",,,,True
ffbd7555a337706238c211197b221795e4e35146,medrxiv,Estimation of COVID-2019 burden and potential for international dissemination of infection from Iran,doi.org/10.1101/2020.02.24.20027375,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The Coronavirus Disease 2019 (COVID-19) epidemic began in Wuhan, China in late 2019 and continues to spread globally, with exported cases confirmed in 28 countries at the time of writing. During the interval between February 19 and 23, 2020, Iran reported its first 43 cases with eight deaths.  Three exported cases originating in Iran were identified, suggesting a underlying burden of disease in that country than is indicated by reported cases.  A large epidemic in Iran could further fuel global dissemination of COVID-19.  We sought to estimate COVID-19 outbreak size in Iran based on known exported case counts and air travel links between Iran and other countries, and to anticipate where infections originating in Iran may spread to next.  We assessed interconnectivity between Iran and other countries using using International Air Transport Association (IATA) data.  We used the methods of Fraser et al. to estimate the size of the underlying epidemic that would result in cases being observed  in the United Arab Emirates (UAE), Lebanon, and Canada.  Time at risk estimates were based on a presumed 6 week epidemic age, and length of stay data for visitors to Iran derived from the United Nations World Tourism Organization (UNWTO).  We evaluated the relationship between the strength of travel links with Iran, and destination country rankings on the Infectious Disease Vulnerability Index (IDVI), a validated metric that estimates the capacity of a country to respond to an infectious disease outbreak . Scores range between 0-1, with higher scores reflecting greater capacity to manage infectious outbreaks. UAE, Lebanon, and Canada ranked 3rd, 21st, and 31st, respectively, for outbound air travel volume from Iran in February 2019. We estimated that 18,300 (95% confidence interval: 3770 to 53,470) COVID-19 cases would have had to occur in Iran, assuming an outbreak duration of 1.5 months in the country, in order to observe these three internationally exported cases reported at the time of writing.  Results were robust under varying assumptions about undiagnosed case numbers in Syria, Azerbaijan and Iraq.  Even if it were assumed that all cases were identified in all countries with certainty, the ""best case"" outbreak size was substantial (1820, 95% CI: 380-5320 cases), and far higher than reported case counts.  Given the low volumes of air travel to countries with identified cases of COVID-19 with origin in Iran (such as Canada), it is likely that Iran is currently experiencing a COVID-19 epidemic of significant size for such exportations to be occurring. This is concerning, both for public health in Iran itself, and because of the high likelihood for outward dissemination of the epidemic to neighbouring countries with lower capacity to respond to infectious diseases epidemics.</jats:p>",2020-02-25,"['Ashleigh R. Tuite', 'Isaac Bogoch', 'Ryan Sherbo', 'Alexander Watts', 'David N. Fisman', 'Kamran Khan']",,,,True
c1ae608c7ffb926a0f50a6a34c0780983274ea74,medrxiv,Estimate the incubation period of coronavirus 2019 (COVID-19),doi.org/10.1101/2020.02.24.20027474,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Motivation: Wuhan pneumonia is an acute infectious disease caused by the 2019 novel coronavirus (COVID-19). It is being treated as a Class A infectious disease though it was classified as Class B according to the Infectious Disease Prevention Act of China. Accurate estimation of the incubation period of the coronavirus is essential to the prevention and control. However, it remains unclear about its exact incubation period though it is believed that symptoms of COVID-19 can appear in as few as 2 days or as long as 14 or even more after exposure. The accurate incubation period calculation requires original chain-of-infection data that may not be fully available in the Wuhan regions. In this study, we aim to accurately calculate the incubation period of COVID-19 by taking advantage of the chain-of-infection data, which is well-documented and epidemiologically informative, outside the Wuhan regions. Methods: We acquired and collected officially reported COVID-19 data from 10 regions in China except for Hubei province. To achieve the accurate calculation of the incubation period, we only involved the officially confirmed cases with a clear history of exposure and time of onset. We excluded those without relevant epidemiological descriptions, working or living in Wuhan for a long time, or hard to determine the possible exposure time. We proposed a Monte Caro simulation approach to estimate the incubation of COVID-19 as well as employed nonparametric ways. We also employed manifold learning and related statistical analysis to decipher the incubation relationships between different age/gender groups. Result: The incubation period of COVID-19 did not follow general incubation distributions such as lognormal, Weibull, and Gamma distributions. We estimated that the mean and median of its incubation were 5.84 and 5.0 days via bootstrap and proposed Monte Carlo simulations.  We found that the incubation periods of the groups with age&gt;=40 years and age&lt;40 years demonstrated a statistically significant difference. The former group had a longer incubation period and a larger variance than the latter. It further suggested that different quarantine time should be applied to the groups for their different incubation periods. Our machine learning analysis also showed that the two groups were linearly separable. incubation of COVID-19 along with previous statistical analysis. Our results further indicated that the incubation difference between males and females did not demonstrate a statistical significance.</jats:p>",2020-02-29,['Henry Han'],,,,True
7b5be48b7769ccad2f44a8c54efcea5281a6c633,medrxiv,"Spread and control of COVID-19 in China and their associations with population movement, public health emergency measures, and medical resources",doi.org/10.1101/2020.02.24.20027623,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>ABSTRACT  BACKGROUND The COVID-19 epidemic, first emerged in Wuhan during December 2019, has spread globally. While the mass population movement for Chinese New Year has significantly influenced spreading the disease, little direct evidence exists about the relevance to epidemic and its control of population movement from Wuhan, local emergency response, and medical resources in China.  METHODS Spearman's correlation analysis was performed between official data of confirmed COVID-19 cases from Jan 20th to Feb 19th, 2020 and real-time travel data and health resources data.   RESULTS There were 74,675 confirmed COVID-19 cases in China by Feb 19th, 2020. The overall fatality rate was 2.84%, much higher in Hubei than in other regions (3.27% vs 0.73%). The index of population inflow from Hubei was positively correlated with total (Provincial r=0.9159, p&lt;0.001; City r=0.6311, p&lt;0.001) and primary cases (Provincial r=0.8702, p&lt;0.001; City r=0.6358, p&lt;0.001). The local health emergency measures (eg, city lockdown and traffic control) were associated with reduced infections nationwide. Moreover, the number of public health employees per capita was inversely correlated with total cases (r=-0.6295, p&lt;0.001) and infection rates (r=-0.4912, p&lt;0.01). Similarly, cities with less medical resources had higher fatality (r=-0.4791, p&lt;0.01) and lower cure rates (r=0.5286, p&lt;0.01) among the confirmed cases.  CONCLUSIONS The spread of the COVID-19 in China in its early phase was attributed primarily to population movement from Hubei, and effective governmental health emergency measures and adequate medical resources played important roles in subsequent control of epidemic and improved prognosis of affected individuals.</jats:p>",2020-02-27,"['Songmin Ying', 'Fei Li', 'Xinwei Geng', 'Zhouyang Li', 'Xufei Du', 'Haixia Chen', 'Sisi Chen', 'Min Zhang', 'Zhehua Shao', 'Yinfang Wu', 'Madiha Zahra Syeda', 'Fugui Yan', 'Luanqing Che', 'Bin Zhang', 'Jian Lou', 'Shaobin Wang', 'Zhengming Chen', 'Wen Li', 'Ye Shen', 'Zhihua Chen', 'Huahao Shen']",,,,True
d7701711485f822c0f43df58b48faf6a433028c4,medrxiv,"Transmission potential of the novel coronavirus (COVID-19) onboard the Diamond Princess Cruises Ship, 2020",doi.org/10.1101/2020.02.24.20027649,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>An outbreak of COVID-19 developed aboard the Princess Cruises Ship during January-February 2020. Using mathematical modeling and time-series incidence data describing the trajectory of the outbreak among passengers and crew members, we characterize how the transmission potential varied over the course of the outbreak. Our estimate of the mean reproduction number in the confined setting reached values as high as ~11, which is higher than mean estimates reported from community-level transmission dynamics in China and Singapore (approximate range: 1.1-7). Our findings suggest that Rt decreased substantially compared to values during the early phase after the Japanese government implemented an enhanced quarantine control. Most recent estimates of Rt reached values largely below the epidemic threshold, indicating that a secondary outbreak of the novel coronavirus was unlikely to occur aboard the Diamond Princess Ship.</jats:p>",2020-02-27,"['Kenji Mizumoto', 'Gerardo Chowell']",,,,True
e560b24612be7e9f4c601e9ad4dde30c19ebcbbb,medrxiv,Deep learning-based model for detecting 2019 novel coronavirus pneumonia on high-resolution computed tomography: a prospective study,doi.org/10.1101/2020.02.25.20021568,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Computed tomography (CT) is the preferred imaging method for diagnosing 2019 novel coronavirus (COVID19) pneumonia. Our research aimed to construct a system based on deep learning for detecting COVID-19 pneumonia on high resolution CT, relieve working pressure of radiologists and contribute to the control of the epidemic. Methods: For model development and validation, 46,096 anonymous images from 106 admitted patients, including 51 patients of laboratory confirmed COVID-19 pneumonia and 55 control patients of other diseases in Renmin Hospital of Wuhan University (Wuhan, Hubei province, China) were retrospectively collected and processed. Twenty-seven consecutive patients undergoing CT scans in Feb, 5, 2020 in Renmin Hospital of Wuhan University were prospectively collected to evaluate and compare the efficiency of radiologists against 2019-CoV pneumonia with that of the model. Findings: The model achieved a per-patient sensitivity of 100%, specificity of 93.55%, accuracy of 95.24%, PPV of 84.62%, and NPV of 100%; a per-image sensitivity of 94.34%, specificity of 99.16%, accuracy of 98.85%, PPV of 88.37%, and NPV of 99.61% in retrospective dataset. For 27 prospective patients, the model achieved a comparable performance to that of expert radiologist. With the assistance of the model, the reading time of radiologists was greatly decreased by 65%. Conclusion: The deep learning model showed a comparable performance with expert radiologist, and greatly improve the efficiency of radiologists in clinical practice. It holds great potential to relieve the pressure of frontline radiologists, improve early diagnosis, isolation and treatment, and thus contribute to the control of the epidemic.</jats:p>",2020-02-26,"['Jun Chen', 'Lianlian Wu', 'Jun Zhang', 'Liang Zhang', 'Dexin Gong', 'Yilin Zhao', 'Shan Hu', 'Yonggui Wang', 'Xiao Hu', 'Biqing Zheng', 'Kuo Zhang', 'Huiling Wu', 'Zehua Dong', 'Youming Xu', 'Yijie Zhu', 'Xi Chen', 'Lilei Yu', 'Honggang Yu']",,,,False
da5ecffba8c5d1b7afee057ff61149fb976501ce,medrxiv,"Highland of COVID-19 outside Hubei: epidemic characteristics, control and projections of Wenzhou, China",doi.org/10.1101/2020.02.25.20024398,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>In late December 2019, Chinese authorities reported a cluster of pneumonia cases of unknown aetiology in Wuhan, China. Wenzhou, as a southeast coastal city with the most cases outside Hubei Province, its policy control and epidemic projections have certain references for national and worldwide epidemic prevention and control. The maximum number of illness onset in Wenzhou appeared on January 26 (38 cases). Since January 27, the incidence per day in Wenzhou has continued to decline is likely to be due to isolation of people return to Wenzhou, implementation of region quarantine and suspension of public transportation system. Under the current control efforts, we estimate that the daily incidence by March 3-9, 2020 will drop to 0 in Wenzhou using SEIR model. The total number of affected people is 538.</jats:p>",2020-02-29,"['Liangde Xu', 'Jian Yuan', 'Yaru Zhang', 'Guosi Zhang', 'Fan Lu', 'Jianzhong Su', 'Jia Qu']",,,,True
bca15ad98e1d08c6a62c9c0486de84bc15a9f661,medrxiv,Can routine laboratory tests discriminate 2019 novel coronavirus infected pneumonia from other community-acquired pneumonia?,doi.org/10.1101/2020.02.25.20024711,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background. The clinical presentation of 2019 Novel Coronavirus (2019-nCov) infected pneumonia (NCIP) resembles that of other etiologies of community-acquired pneumonia (CAP). We aimed to identify clinical laboratory features to distinguish NCIP from CAP. Methods. We compared the ability of the hematological and biochemical features of 84 patients with NCIP at hospital admission and 316 patients with CAP. Parameters independently predictive of NCIP were calculated by multivariate logistic regression. The receiver operating characteristic (ROC) curves were generated and the area under the ROC curve (AUC) was measured to evaluate the discriminative ability. Results. Most hematological and biochemical indexes of patients with NCIP were significantly different from patients with CAP. Nine laboratory parameters were identified to be highly predictive of a diagnosis of NCIP by multivariate analysis. The AUCs demonstrated good discriminatory ability for red cell distribution width (RDW) with an AUC of 0.88 and Hemoglobin (HGB) with an AUC of 0.82. Red blood cell (RBC), albumin (ALB), eosinophil (EO), hematocrit (HCT), alkaline phosphatase (ALP), and white blood cell (WBC) had fair discriminatory ability. Combinations of any two parameters performed better than did the RDW alone. Conclusions. Routine laboratory examinations may be helpful for the diagnosis of NCIP. Application of laboratory tests may help to optimize the use of isolation rooms for patients when they present with unexplained febrile respiratory illnesses.</jats:p>",2020-02-25,"['Yunbao Pan', 'Guangming Ye', 'Xiantao Zeng', 'Guohong Liu', 'Xiaojiao Zeng', 'Xianghu Jiang', 'Jin Zhao', 'Liangjun Chen', 'Shuang Guo', 'Qiaoling Deng', 'Xiaoyue Hong', 'Ying Yang', 'Yirong Li', 'Xinghuan Wang']",,,,True
c8d206a4f9af0709b6e9ee90c4d854d482cb0784,medrxiv,Correlation Analysis Between Disease Severity and Inflammation-related Parameters in Patients with COVID-19 Pneumonia,doi.org/10.1101/2020.02.25.20025643,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Aim: The new coronavirus pneumonia (COVID-19) outbreaking at the end of 2019 is highly contagious. Crude mortality rate reached 49% in critical patients. Inflammation matters on disease progression. This study analyzed blood inflammation indicators among mild, severe and critical patients, helping to identify severe or critical patients early. Methods: In this cross-sectional study, 100 patients were included and divided to mild, severe or critical groups. Correlation of peripheral blood inflammation-related indicators with disease criticality was analyzed. Cut-off values for critically ill patients were speculated through the ROC curve. Results：Significantly, disease severity were associated with age (R=-0.564, P&lt;0.001), interleukin-2 receptor (IL2R) (R=-0.534, P&lt;0.001), interleukin-6 (IL-6) (R=-0.535, P&lt;0.001), interleukin-8 (IL-8) (R=-0.308, P&lt;0.001), interleukin-10 (IL-10) (R=-0.422, P&lt;0.001), tumor necrosis factor α (TNFα) (R=-0.322, P&lt;0.001), C-reactive protein (CRP) (R=-0.604, P&lt;0.001), ferroprotein (R=-0.508, P&lt;0.001), procalcitonin (R=-0.650, P&lt;0.001), white cell counts (WBC) (R=-0.54, P&lt;0.001), lymphocyte counts (LC) (R=-0.56, P&lt;0.001), neutrophil count (NC) (R=-0.585, P&lt;0.001) and eosinophil counts (EC) (R=-0.299, P=0.01). Conclusion：With following parameters such as age &gt;67.5 years, IL2R &gt;793.5U/mL, CRP &gt;30.7ng/mL, ferroprotein &gt;2252μg/L, WBC&gt;9.5*10^9/L or NC &gt;7.305*10^9/L, the progress of COVID-19 to critical stage should be closely observed and possibly prevented. Inflammation is closely related to severity of COVID-19, and IL-6, TNFα and IL-8 might be promising therapeutic targets.</jats:p>",2020-02-27,"['Jing Gong', 'Hui Dong', 'Song Qing Xia', 'Yi Zhao Huang', 'Dingkun Wang', 'Yan Zhao', 'Wenhua Liu', 'Shenghao Tu', 'Mingmin Zhang', 'Qi Wang', 'Fuer Lu']",,,,True
7d3dcbbc2b0741fc544693d7b3fc185f0bd50eac,medrxiv,Open-source analytics tools for studying the COVID-19 coronavirus outbreak,doi.org/10.1101/2020.02.25.20027433,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>To provide convenient access to epidemiological data on the coronavirus outbreak, we developed an R package, nCov2019 (https://github.com/GuangchuangYu/nCov2019). Besides detailed real-time statistics, it offers access to three data sources with detailed daily statistics from December 1, 2019, for 43 countries and more than 500 Chinese cities. We also developed a web app (http://www.bcloud.org/e/) with interactive plots and simple time-series forecasts. These analytics tools could be useful in informing the public and studying how this and similar viruses spread in populous countries.</jats:p>",2020-02-27,"['Tianzhi Wu', 'Xijin Ge', 'Guangchuang Yu', 'Erqiang Hu']",,,,True
160ecaaa5a766c289fc2f6b5499f0dfe7aab971c,medrxiv,Stochastic discrete epidemic modeling of COVID-19 transmission in the Province of Shaanxi incorporating public health intervention and case importation,doi.org/10.1101/2020.02.25.20027615,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Before the lock-down of Wuhan/Hubei/China, on January 23rd 2020, a large number of individuals infected by COVID-19 moved from the epicenter Wuhan and the Hubei province due to the Spring Festival, resulting in an epidemic in the other provinces including the Shaanxi province. The epidemic scale in Shaanxi was comparatively small and with half of cases being imported from the epicenter. Based on the complete epidemic data including the symptom onset time and transmission chains, we calculate the control reproduction number (1.48-1.69) in Xian. We could also compute the time transition, for each imported or local case, from the latent, to infected, to hospitalized compartment, as well as the effective reproduction number. This calculation enables us to revise our early deterministic transmission model to a stochastic discrete epidemic model with case importation and parameterize it. Our model-based analyses reveal that the newly generated infections decay to zero quickly; the cumulative number of case-driven quarantined individuals via contact tracing stabilize at a manageable level, indicating that the intervention strategies implemented in the Shaanxi province have been effective. Risk analyses, important for the consideration of resumption of work, show that a large second outbreak is expected if the level of case importation remains at the same level as between January 10th and February 4th 2020. However, if the case importation decreases by 30%, 60% and 90%, the second outbreak if happening will be of small-scale assuming contact tracing and quarantine/isolation remain as effective as before. Finally, we consider the effects of intermittent inflow with a Poisson distribution on the likelihood of multiple outbreaks. We believe the developed methodology and stochastic model provide an important model framework for the evaluation of revising travel restriction rules in the consideration of resuming social-economic activities while managing the disease control with potential case importation.</jats:p>",2020-02-29,"['Sanyi Tang', 'Biao Tang', 'Nicola Luigi Bragazzi', 'Fan Xia', 'Tangjuan Li', 'Sha He', 'Pengyu Ren', 'Xia Wang', 'Zhihang Peng', 'Yanni Xiao', 'Jianhong Wu']",,,,True
875b7c463f00772fa0dc18ada678bc1ff16a4274,medrxiv,"Comorbidity and its impact on 1,590 patients with COVID-19 in China: A Nationwide Analysis",doi.org/10.1101/2020.02.25.20027664,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: To evaluate the spectrum of comorbidities and its impact on the clinical outcome in patients with coronavirus disease 2019 (COVID-19). Design: Retrospective case studies Setting: 575 hospitals in 31 province/autonomous regions/provincial municipalities across China Participants: 1,590 laboratory-confirmed hospitalized patients. Data were collected from November 21st, 2019 to January 31st, 2020. Main outcomes and measures: Epidemiological and clinical variables (in particular, comorbidities) were extracted from medical charts. The disease severity was categorized based on the American Thoracic Society guidelines for community-acquired pneumonia. The primary endpoint was the composite endpoints, which consisted of the admission to intensive care unit (ICU), or invasive ventilation, or death. The risk of reaching to the composite endpoints was compared among patients with COVID-19 according to the presence and number of comorbidities. Results: Of the 1,590 cases, the mean age was 48.9 years. 686 patients (42.7%) were females. 647 (40.7%) patients were managed inside Hubei province, and 1,334 (83.9%) patients had a contact history of Wuhan city. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached to the composite endpoints. 399 (25.1%) reported having at least one comorbidity. 269 (16.9%), 59 (3.7%), 30 (1.9%), 130 (8.2%), 28 (1.8%), 24 (1.5%), 21 (1.3%), 18 (1.1%) and 3 (0.2%) patients reported having hypertension, cardiovascular diseases, cerebrovascular diseases, diabetes, hepatitis B infections, chronic obstructive pulmonary disease, chronic kidney diseases, malignancy and immunodeficiency, respectively. 130 (8.2%) patients reported having two or more comorbidities. Patients with two or more comorbidities had significantly escalated risks of reaching to the composite endpoint compared with those who had a single comorbidity, and even more so as compared with those without (all P&lt;0.05). After adjusting for age and smoking status, patients with COPD (HR 2.681, 95%CI 1.424-5.048), diabetes (HR 1.59, 95%CI 1.03-2.45), hypertension (HR 1.58, 95%CI 1.07-2.32) and malignancy (HR 3.50, 95%CI 1.60-7.64) were more likely to reach to the composite endpoints than those without. As compared with patients without comorbidity, the HR (95%CI) was 1.79 (95%CI 1.16-2.77) among patients with at least one comorbidity and 2.59 (95%CI 1.61-4.17) among patients with two or more comorbidities. Conclusion: Comorbidities are present in around one fourth of patients with COVID-19 in China, and predispose to poorer clinical outcomes.</jats:p>",2020-02-27,"['Wei-jie Guan', 'Wen-hua Liang', 'Yi Zhao', 'Heng-rui Liang', 'Zi-sheng Chen', 'Yi-min Li', 'Xiao-qing Liu', 'Ru-chong Chen', 'Chun-li Tang', 'Tao Wang', 'Chun-quan Ou', 'Li Li', 'Ping-yan Chen', 'Ling Sang', 'Wei Wang', 'Jian-fu Li', 'Cai-chen Li', 'Li-min Ou', 'Bo Cheng', 'Shan Xiong', 'Zheng-yi Ni', 'Yu Hu', 'Jie Xiang', 'Lei Liu', 'Hong Shan', 'Chun-liang Lei', 'Yi-xiang Peng', 'Li Wei', 'Yong Liu', 'Ya-hua Hu', 'Peng Peng', 'Jian-ming Wang', 'Ji-yang Liu', 'Zhong Chen', 'Gang Li', 'Zhi-jian Zheng', 'Shao-qin Qiu', 'Jie Luo', 'Chang-jiang Ye', 'Shao-yong Zhu', 'Lin-ling Cheng', 'Feng Ye', 'Shi-yue Li', 'Jin-ping Zheng', 'Nuo-fu Zhang', 'Nan-shan Zhong', 'Jian-xing He']",,,,True
22dcb31779bd6c5f70ff99d16706b6be06e67b89,medrxiv,Age-dependent risks of Incidence and Mortality of COVID-19 in Hubei Province and Other Parts of China,doi.org/10.1101/2020.02.25.20027672,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>New coronavirus SARS-CoV-2 poses a big challenge for global public health in early 2020. Coronavirus Disease 2019 (COVID-19) caused by the virus rapidly spreads all over the world and takes thousands of lives in just two months. It is critical to refine the incidence and mortality risks of COVID-19 for the effective management of the general public and patients in the outbreak. In this report, we investigate the incidence and mortality risks of the infection by analyzing the age composition of 5319 infected patients, 76 fatal cases, and 1,144,648 individuals of the general public in China. Our result shows a relatively low incidence risk for young people but a very high mortality risk for seniors. Notably, mortality risk could be as high as 0.48 for people older than 80 years. Furthermore, our study suggests that a good medical service can effectively reduce the mortality rate of the viral infection to 1% or less.</jats:p>",2020-02-27,"['Hongdou Li', 'Shuang Wang', 'Fan Zhong', 'Wuyin Bao', 'Yipeng Li', 'Lei Liu', 'Hongyan Wang', 'Yungang He']",,,,False
e046a06f262d74d025272ad697d358c4afb5d9bd,medrxiv,Application and optimization of RT-PCR in diagnosis of SARS-CoV-2 infection,doi.org/10.1101/2020.02.25.20027755,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Coronavirus Disease 2019 (COVID-19) caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global threat to public health. Aiming to construct an efficient screening pattern, we comprehensively evaluated the performances of RT-PCR and chest CT in diagnosing COVID-19.  Methods: The records including demographics, RT-PCR, and CT from 87 confirmed COVID-19 cases and 481 exclusion cases were collected. The diagnostic accuracy of the pharyngeal swab RT-PCR, CT, combination with the second pharyngeal swab RT-PCR or with CT were evaluated individually. Besides, all the stool RT-PCR results were plotted by time to explore the value of stool RT-PCR. Findings: Combination of RT-PCR and CT has the higher sensitivity (91.9%,79/86) than RT-PCR alone (78.2%，68/87) or CT alone (66.7%, 54 of 81) or combination of two RT-PCR tests (86.2%,75/87). There was good agreement between RT-PCR and CT (kappa-value, 0.430). In 34 COVID-19 cases with inconsistent results, 94.1% (n=32) are mild infection, 62.5% of which (20/32) showed positive RT-PCR. 46.7% (35/75) COVID-19 patients had at least one positive stool during the course. Two cases had positive stool earlier than the pharyngeal swabs. Importantly, one patient had consecutive positive stool but negative pharyngeal swabs. Interpretation: Combination of RT-PCR and CT with the highest sensitivity is an optimal pattern to screen COVID-19. RT-PCR is superior to CT in diagnosing mild infections. Stool RT-PCR should be considered as an item for improving discovery rate and hospital discharge. This study shed light for optimizing scheme of screening and monitoring of SARS-CoV-2 infection.</jats:p>",2020-02-27,"['Guanmin Jiang', 'Xiaoshuai Ren', 'Yan Liu', 'Hongtao Chen', 'Wei Liu', 'Zhaowang Guo', 'Yaqin Zhang', 'Chaoqun Chen', 'Jianhui Zhou', 'Qiang Xiao', 'Hong Shan']",,,,True
0eee9760aee0ca2fdf8d1d215c3689d5f8d84df5,medrxiv,"Prevalence and clinical features of 2019 novel coronavirus disease (COVID-19) in the Fever Clinic of a teaching hospital in Beijing: a single-center, retrospective study",doi.org/10.1101/2020.02.25.20027763,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background With the spread of COVID-19 from Wuhan, Hubei Province to other areas of the country, medical staff in Fever Clinics faced the challenge of identifying suspected cases among patients with respiratory infections manifested with fever. We aimed to describe the prevalence and clinical features of COVID-19 as compared to pneumonias of other etiologies in a Fever Clinic in Beijing. Methods In this single-center, retrospective study, 342 cases of pneumonia were diagnosed in Fever Clinic in Peking University Third Hospital between January 21 to February 15, 2020. From these patients, 88 were reviewed by panel discussion as possible or probable cases of COVID-19, and received 2019-nCoV detection by RT-PCR. COVID-19 was confirmed by positive 2019-nCoV in 19 cases, and by epidemiological, clinical and CT features in 2 cases (the COVID-19 Group, n=21), while the remaining 67 cases served as the non-COVID-19 group. Demographic and epidemiological data, symptoms, laboratory and lung CT findings were collected, and compared between the two groups. Findings The prevalence of COVID-19 in all pneumonia patients during the study period was 6.14% (21/342). Compared with the non-COVID-19 group, more patients with COVID-19 had an identified epidemiological history (90.5% versus 32.8%, P&lt;0.001). The COVID-19 group had lower WBC [5.19×10^9/L (±1.47) versus 7.21×10^9/L (±2.94), P&lt;0.001] and neutrophil counts [3.39×10^9/L (±1.48) versus 5.38×10^9/L (±2.85), P&lt;0.001] in peripheral blood. However, the percentage and count of lymphocytes were not different. On lung CT scans, involvement of 4 or more lobes was more common in the COVID-19 group (45% versus 16.4%, P=0.008).  Interpretation In the period of COVID-19 epidemic outside Hubei Province, the prevalence of COVID-19 in patients with pneumonia visiting to our Fever Clinic in Beijing was 6.14%. Epidemiological evidence was important for prompt case finding, and lower blood WBC and neutrophil counts may be useful for differentiation from pneumonia of other etiologies.</jats:p>",2020-02-27,"['Ying Liang', 'Jingjin Liang', 'Qingtao Zhou', 'Xiaoguang Li', 'Fei Lin', 'Zhonghua Deng', 'Biying Zhang', 'Lu Li', 'Xiaohua Wang', 'Hong Zhu', 'Qingbian Ma', 'Xiaomei Tong', 'Jie Xu', 'Yongchang Sun']",,,,True
532ece4e50c7e57edd88787f52459d9bba5bcc31,medrxiv,Genomic variations of SARS-CoV-2 suggest multiple outbreak sources of transmission,doi.org/10.1101/2020.02.25.20027953,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>We examined 169 genomes of SARS-CoV-2 and found that they can be classified into two major genotypes, Type I and Type II. Type I can be further divided into Type IA and IB. Our phylogenetic analysis showed that the Type IA resembles the ancestral SARS-CoV-2 most. Type II was likely evolved from Type I and predominant in the infections. Our results suggest that Type II SARS-CoV-2 was the source of the outbreak in the Wuhan Huanan market and it was likely originated from a super-spreader. The outbreak caused by the Type I virus should have occurred somewhere else, because the patients had no direct link to the market. Furthermore, by analyzing three genomic sites that distinguish Type I and Type II strains, we found that synonymous changes at two of the three sites confer higher protein translational efficiencies in Type II strains than in Type I strains, which might explain why Type II strains are predominant, implying that Type II is more contagious (transmissible) than Type I. These findings could be valuable for the current epidemic prevention and control.</jats:p>",2020-02-26,"['Liangsheng Zhang', 'Jian-Rong Yang', 'Zhenguo Zhang', 'Zhenguo Lin']",,,,False
eca1cf50bd67a7efbcaf78864f5f5b3b850243d6,medrxiv,Clinical Data on Hospital Environmental Hygiene Monitoring and Medical Staff Protection during the Coronavirus Disease 2019 Outbreak,doi.org/10.1101/2020.02.25.20028043,,,See https://www.medrxiv.org/submit-a-manuscript,<jats:p>Background: The outbreak of coronavirus disease 2019 (COVID-19) has placed unprecedented challenges on hospital environmental hygiene and medical staff protection. It is crucial to assess hospital environmental hygiene to understand the most important environmental issues for controlling the spread of COVID-19 in hospitals.  Objective: To detect the presence of COVID-19 in the samples from the area at risk of contamination in the First Hospital of Jilin University. Methods: Viruses in the air were collected by natural sedimentation and air particle sampler methods. Predetermined environmental surfaces were sampled using swabs at seven o'clock in the morning before disinfection. The real-time reverse-transcription PCR method was used to detect the existence of COVID-19 pathogens. Results: Viruses could be detected on the surfaces of the nurse station in the isolation area with suspected patients and in the air of the isolation ward with an intensive care patient. Conclusion: Comprehensive monitoring of hospital environmental hygiene during pandemic outbreaks is conducive to the refinement of hospital infection control. It is of great significance to ensure the safety of medical treatment and the quality of hospital infection control through the monitoring of environmental hygiene.</jats:p>,2020-02-27,"['Yanfang Jiang', 'Haifeng Wang', 'Yukun Chen', 'Jiaxue He', 'Liguo Chen', 'Yong Liu', 'Xinyuan Hu', 'Ang Li', 'Siwen Liu', 'Peng Zhang', 'Hongyan Zou', 'Shucheng Hua']",,,,True
baabfb35a321ea12028160e0d2c1552a2fda2dd5,medrxiv,Clinical Features of COVID-19 Related Liver Damage,doi.org/10.1101/2020.02.26.20026971,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>BACKGROUND: A recent outbreak of SARS-CoV-2 infection occurs mainly in China, with rapidly increasing the number of cases (namely COVID-19). Abnormal liver functions are frequently present in these patients, here we aimed to clarify the clinical features of COVID-19-related liver damage to provide some references for the clinical treatment. METHODS: In this retrospective, single-center study, we included all confirmed COVID-19 cases in Shanghai Public Health Clinical Center from January 20 to January 31, 2020. The outcomes were followed up until February 19, 2020. A total of 148 cases were analyzed for clinical features, laboratory parameters (including liver function tests), medications and the length of stay.  FINDINGS: Of 148 confirmed SARS-CoV-2-infected patients, 49.3% were females and 50.7% were males. The median age was 50.5 years (interquartile range, 36-64). Patients had clinical manifestations of fever (70.1%), cough (45.3%), expectoration (26.7%) at admission. 75 patients (50.7%) showed abnormal liver functions at admission. Patients (n = 75) who had elevated liver function index were more likely to have a moderate-high degree fever (44% vs 27.4%; p = 0.035) and significantly present in male patients (62.67% vs 38.36%; p = 0.005). The numbers of  CD4+ and CD8+ T cells were significantly lower in abnormal liver function group than those in normal liver function group. There was no statistical difference in prehospital medications between normal and abnormal liver function groups, while the utilization rate of lopinavir/ritonavir after admission was significantly higher in patients with emerging liver injury than that in patients with normal liver functions. Importantly, the emerging abnormal liver functions after admission caused a prolonged length of stay. INTERPRETATION: SARS-CoV-2 may cause the liver function damage and the Lopinavir/ritonavir should be applied carefully for the treatment of COVID-19.</jats:p>",2020-02-27,"['Zhenyu Fan', 'Liping Chen', 'Jun Li', 'Cheng Tian', 'Yajun Zhang', 'Shaoping Huang', 'Zhanju Liu', 'Jilin Cheng']",,,,True
40a11e5ee7e16e19ec3648b4a17fc09604df287f,medrxiv,The definition and risks of Cytokine Release Syndrome-Like in 11 COVID-19-Infected Pneumonia critically ill patients: Disease Characteristics and Retrospective Analysis,doi.org/10.1101/2020.02.26.20026989,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>IMPORTANCE: COVID-19-infected pneumonia patients with severe immune abnormalities and risk of cytokine release syndrome. The definition, prevention, and treatment of COVID-19-infected pneumonia in critically ill patients with cytokine release syndrome symptoms is an important problem.</jats:p>",2020-02-27,"['Wenjun Wang', 'Jianxing He', 'puyi Lie', 'liyan Huang', 'Sipei Wu', 'yongping lin', 'xiaoqing liu']",,,,False
7344c6de7ce2258e74ce131bed72e6ad465f0ce8,medrxiv,Relations of parameters for describing the epidemic of COVID―19 by the Kermack―McKendrick model,doi.org/10.1101/2020.02.26.20027797,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>In order to quantitatively characterize the epidemic of COVID―19, useful relations among parameters describing an epidemic in general are derived based on the Kermack-McKendrick model. The first relation is 1/<jats:italic>τ<jats:sub>grow</jats:sub></jats:italic>=1/<jats:italic>τ<jats:sub>trans</jats:sub></jats:italic>−1/<jats:italic>τ<jats:sub>inf</jats:sub></jats:italic>, where <jats:italic>τ<jats:sub>grow</jats:sub></jats:italic> is the time constant of the exponential growth of an epidemic, <jats:italic>τ<jats:sub>trans</jats:sub></jats:italic> is the time for a pathogen to be transmitted from one patient to uninfected person, and the infectious time <jats:italic>τ<jats:sub>inf</jats:sub></jats:italic> is the time during which the pathogen keeps its power of transmission. The second relation <jats:italic>p(∞)</jats:italic> ≈1−exp(−(<jats:italic>R<jats:sub>0</jats:sub></jats:italic>−1)/0.60) is the relation between <jats:italic>p(∞)</jats:italic>, the final size of the disaster defined by the ratio of the total infected people to the population of the society,and the basic reproduction number, <jats:italic>R<jats:sub>0</jats:sub></jats:italic>, which is the number of persons infected by the transmission of the pathogen from one infected person during the infectious time. The third relation 1/<jats:italic>τ<jats:sub>end</jats:sub></jats:italic>=1/<jats:italic>τ<jats:sub>inf</jats:sub></jats:italic>−(1−<jats:italic>p</jats:italic>(∞))/<jats:italic>τ<jats:sub>trans</jats:sub></jats:italic> gives the decay time constant <jats:italic>τ<jats:sub>end</jats:sub></jats:italic> at the ending stage of the epidemic. Derived relations are applied to influenza in Japan in 2019 for characterizing the epidemic.</jats:p>",2020-03-03,['Toshihisa Tomie'],,,,True
c10661c9b35e068691b879661bcebeba3bd6aad9,medrxiv,The infection evidence of SARS-COV-2 in ocular surface： a single-center cross-sectional study,doi.org/10.1101/2020.02.26.20027938,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Purpose: The aim of this study was to identify whether SARS-COV-2 infected in ocular surface.  Methods: Cross-sectional study of patients presenting for who received a COVID-19 diagnosis, from December 30, 2019 to February 7, 2020, at Tongji hospital, Tongji medical college, Huazhong University of Science and Technology. Demographics, temperature was recorded, blood routine test (Rt), chest Computed Tomography (CT) were took intermittently, and SARS-COV-2 real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay were arranged for the nasopharyngeal and conjunctival swab samples.  Results: A total of 102 patients (48 Male [50%] and 54 Female [50%]) with clinical symptoms, Rt, and chest Computed Tomography (CT) abnormalities were identified with a clinical diagnosis of COVID-19. Patients had a mean [SD] gestational age of 57.63 [14.90] years. Of a total of 102 patients identified, 72 patients (36 men [50%] and 36 women [50%]; mean [SD] age, 58.68 [14.81] years) confirmed by laboratory diagnosis with SARS-COV-2 RT-PCR assay. Only two patients (2.78%) with conjunctivitis was identified from 72 patients with a laboratory confirmed COVID-19. However, SARS-COV-2 RNA fragments was found in ocular discharges by SARS-COV-2 RT-PCR only in one patient with conjunctivitis. Conclusions: Although we suspect the incidence of SARS-COV-2 infection through the ocular surface is extremely low, the nosocomial infection of SARS-CoV-2 through the eyes after occupational exposure is a potential route. The inefficient diagnostic method and the sampling time lag may contribute to the lower positive rate of conjunctival swab samples of SARS-COV-2. Therefore, to lower the SARS-COV-2 nosocomial infection, the protective goggles should be wore in all the health care workers.</jats:p>",2020-02-26,"['Xufang Sun', 'Xian Zhang', 'Xuhui Chen', 'Liwen Chen', 'Chaohua Deng', 'Xiaojing Zou', 'Weiyong Liu', 'Huimin Yu']",,,,True
46634d03aa169aab9c372746ebaf3aaa65d7c7d9,medrxiv,Case fatality rate of novel coronavirus disease 2019 in China,doi.org/10.1101/2020.02.26.20028076,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Abstract Background: A pandemic of coronavirus disease 2019 (COVID-19) which have caused more than 80 thousand persons infected globally is still ongoing. This study aims to calculate its case fatality rate (CFR). Methods: The method, termed as converged CFR calculation, was based on the formula of dividing the number of known deaths by the number of confirmed cases T days before, where T was an average time period from case confirmation to death. It was found that supposing a T, if it was smaller (bigger) than the true T, calculated CFRs would gradually increase (decrease) to infinitely near the true T with time went on. According to the law, the true T value could be determined by trends of daily CFRs calculated with different assumed T values (left of true T is decreasing, right is increasing). Then the CFR could be calculated. Results: CFR of COVID-19 in China except Hubei Province was 0.8% to 0.9%. So far, the CFR had accurately predicted the death numbers more than 3 weeks. CFR in Hubei of China was 5.4% by which the calculated death number corresponded with the reported number for 2 weeks. Conclusion: The method could be used for CFR calculating while pandemics are still ongoing. Dynamic monitoring of the daily CFRs trends could help outbreak-controller to have a clear vision in the timeliness of the case confirmation.</jats:p>",2020-02-26,"['Rui Qi', 'Chao Ye', 'Xiang-rong Qin', 'Xue-Jie Yu']",,,,True
c954675ee859e2f7b8f352a398a67469b50f05de,medrxiv,Evaluation of the clinical characteristics of suspected or confirmed cases of COVID-19 during home care with isolation: A new retrospective analysis based on O2O,doi.org/10.1101/2020.02.26.20028084,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Summary Background The recent outbreak of the novel coronavirus in December 2019 (COVID-19) has activated top-level response nationwide. We developed a new treatment model based on the online-to-offline (O2O) model for the home isolated patients, because in the early stages the medical staff were insufficient to cope with so many patients. Methods In this single-centered, retrospective study, we enrolled 48 confirmed/suspected COVID-19 patients who underwent home isolation in Wuhan between January 6 and January 31, 2020. By WeChat and online document editing all patients were treated with medical observation scale. The clinical indications such as Fever, Muscle soreness, Dyspnea and Lack of strength were collected with this system led by medical staff in management, medicine, nursing, rehabilitation and psychology.  Findings The mean(SD) age of 48 patients was 39.08(13.88) years, 35(72.9%) were women. Compared with non-hospitalized patients, inpatients were older(≥8805;70years, 2.4% vs 33.3%, P&lt;0.04). All inpatients had fever, 50% inpatients had coughs and showed infiltration in both lungs at the time of diagnosis. 33.3% inpatients exhibited negative changes in their CT results at initial diagnosis. The body temperature of non-hospitalized patients with mild symptoms returned to normal by day 4-5. While dyspnea peaked on day 6 for non-hospitalized patients with mild symptoms, it persisted in hospitalized patients and exacerbated over time. The lack of strength and muscle soreness were both back to normal by day 4 for non-hospitalized patients. Interpretation Monitoring the trends of symptoms is more important for identifying severe cases. Excessive laboratory data and physical examination are not necessary for the evaluation of patients with mild symptoms. The system we developed is the first to convert the subjective symptoms of patients into objective scores. This type of O2O, subjective-to-objective strategy may be used in regions with similar highly infectious diseases to minimize the possibility of infection among medical staff.</jats:p>",2020-02-29,"['Hui Xu', 'Sufang Huang', 'Shangkun Liu', 'Juan Deng', 'Bo Jiao', 'Ling Ai', 'Yaru Xiao', 'Li Yan', 'Shusheng Li']",,,,True
2536b83acf84368d7c13be81fe07aa0575115da7,medrxiv,Estimation of country-level basic reproductive ratios for novel Coronavirus (COVID-19) using synthetic contact matrices,doi.org/10.1101/2020.02.26.20028167,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The outbreak of novel coronavirus (COVID-19) has the potential for global spread, infecting large numbers in all countries. In this case, estimating the country-specific basic reproductive ratio is a vital first step in public-health planning. The basic reproductive ratio (<jats:italic>R</jats:italic><jats:sub>0</jats:sub>) is determined by both the nature of pathogen and the network of contacts through which the disease can spread - with this network determined by socio-demographics including age-structure and household composition. Here we focus on the age-structured transmission within the population, using data from China to inform age-dependent susceptibility and synthetic age-mixing matrices to inform the contact network. This allows us to determine the country-specific basic reproductive ratio as a multiplicative scaling of the value from China. We predict that <jats:italic>R</jats:italic><jats:sub>0</jats:sub> will be highest across Eastern Europe and Japan, and lowest across Africa, Central America and South-Western Asia. This pattern is largely driven by the ratio of children to older adults in each country and the observed propensity of clinical cases in the elderly.</jats:p>",2020-02-27,"['Joe Hilton', 'Matt J Keeling']",,,,True
a625e5d6fc8956c231c500a40e887e248a69de61,medrxiv,Clinical characteristics of 82 death cases with COVID-19,doi.org/10.1101/2020.02.26.20028191,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background A recently developing pneumonia caused by SARS-CoV-2 was originated in Wuhan, China, and has quickly spread across the world. We reported the clinical characteristics of 82 death cases with COVID-19 in a single center.  Methods Clinical data on 82 death cases laboratory-confirmed as SARS-CoV-2 infection were obtained from a Wuhan local hospital′s electronic medical records according to previously designed standardized data collection forms.  Findings All patients were local residents of Wuhan, and the great proportion of them were diagnosed as severe illness when admitted. Most of the death cases were male (65.9%). More than half of dead patients were older than 60 years (80.5%) and the median age was 72.5 years. The bulk of death cases had comorbidity (76.8%), including hypertension (56.1%), heart disease (20.7%), diabetes (18.3%), cerebrovascular disease (12.2%), and cancer (7.3%). Respiratory failure remained the leading cause of death (69.5%), following by sepsis syndrome/MOF (28.0%), cardiac failure (14.6%), hemorrhage (6.1%), and renal failure (3.7%). Furthermore, respiratory, cardiac, hemorrhage, hepatic, and renal damage were found in 100%, 89%, 80.5%, 78.0%, and 31.7% of patients, respectively. On the admission, lymphopenia (89.2%), neutrophilia (74.3%), and thrombocytopenia (24.3%) were usually observed. Most patients had a high neutrophil-to-lymphocyte ratio of &gt;5 (94.5%), high systemic immune-inflammation index of &gt;500 (89.2%), increased C-reactive protein level (100%), lactate dehydrogenase (93.2%), and D-dimer (97.1%). A high level of IL-6 (&gt;10 pg/ml) was observed in all detected patients. Median time from initial symptom to death was 15 days (IQR 11-20), and a significant association between aspartate aminotransferase (p=0.002), alanine aminotransferase (p=0.037) and time from initial symptom to death were interestingly observed.  Conclusion Older males with comorbidities are more likely to develop severe disease, even die from SARS-CoV-2 infection. Respiratory failure is the main cause of COVID-19, but either virus itself or cytokine release storm mediated damage to other organ including cardiac, renal, hepatic, and hemorrhage should be taken seriously as well.</jats:p>",2020-02-27,"['Bicheng Zhang', 'Xiaoyang Zhou', 'Yanru Qiu', 'Fan Feng', 'Jia Feng', 'Yifan Jia', 'Hengcheng Zhu', 'Ke Hu', 'Jiasheng Liu', 'Zaiming Liu', 'Shihong Wang', 'Yiping Gong', 'Chenliang Zhou', 'Ting Zhu', 'Yanxiang Cheng', 'Zhichao Liu', 'Hongping Deng', 'Fenghua Tao', 'Yijun Ren', 'Biheng Cheng', 'Ling Gao', 'Xiongfei Wu', 'Lilei Yu', 'Zhixin Huang', 'Zhangfan Mao', 'Qibin Song', 'Bo Zhu', 'Jun Wang']",,,,True
7aa49aa2b76ea92b9265ad9d5a9d9ef0ea585b24,medrxiv,"Community responses during the early phase of the COVID-19 epidemic in Hong Kong: risk perception, information exposure and preventive measures",doi.org/10.1101/2020.02.26.20028217,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Community responses are important for outbreak management during the early phase when non-pharmaceutical interventions are the major preventive options. Therefore, this study aims to examine the psychological and behavioral responses of the community during the early phase of the COVID-19 epidemic in Hong Kong.  Method: A cross-sectional online survey was launched within 36 hours after confirmed COVID-19 cases were first reported. Councilors of all 452 district council constituency areas were approached for survey dissemination. Respondent demographics, anxiety level, risk perception, sources to retrieve COVID-19 information, actual adoption and perceived efficacy of precautionary measures were collected.  Result: Analysis from 1715 complete responses indicated high perceived susceptibility (89%) and high perceived severity (97%). Most respondents were worried about COVID-19 (97%), and had their daily routines disrupted (slightly/greatly: 98%). The anxiety level, measured by the Hospital Anxiety and Depression Scale, was borderline abnormal (9.01). Nearly all respondents were alert to the disease progression (99.5%). The most trusted information sources were doctors (84%), followed by broadcast (57%) and newspaper (54%), but they were not common information sources (doctor: 5%; broadcast: 34%; newspaper: 40%). Only 16% respondents found official websites reliable. Enhanced personal hygiene practices and travel avoidance to China were frequently adopted (&gt;77%) and considered effective (&gt;90%). The adoption of social-distancing measures was lower (39%-88%), and their drivers for greater adoption include: being female (adjusted odds ratio [aOR]:1.27), living in the New Territories (aOR:1.32-1.55), perceived as having good understanding of COVID-19 (aOR:1.84) and being more anxious (aOR:1.07).  Discussion: Risk perception towards COVID-19 in the community was high. Most respondents are alert to the disease progression, and adopt self-protective measures. This study contributes by examining the psycho-behavioral responses of hosts, in addition to the largely studied mechanistic aspects, during the early phase of the current COVID-19 epidemic. The timely psychological and behavioral assessment of the community is useful to inform subsequent interventions and risk communication strategies as the epidemic progresses.</jats:p>",2020-02-27,"['Kin On Kwok', 'Kin Kit Li', 'Ho Hin Chan', 'Yuan Yuan Yi', 'Arthur Tang', 'Wan In Wei', 'Yeung Shan Wong']",,,,True
111b9a6e91c938696fcdb4cb128b8ae739dbe11c,medrxiv,"Clinical features and sexual transmission potential of SARS-CoV-2 infected female patients: a descriptive study in Wuhan, China",doi.org/10.1101/2020.02.26.20028225,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: As of March 2, 2020, SARS-CoV-2 has infected more than 80174 people and caused 2915 deaths in China. This virus rapidly spreads to 56 countries worldwide. Thus, in order to effectively block its transmission, it is urgent to uncover all the possible transmission routes of SARS-CoV-2.  Methods: From January 28 to February 18, 2020, 35 female patients diagnosed with COVID-19 in Tongji Hospital were included in this descriptive study. The gynecologic history, clinical characteristics, laboratory findings and chest computed tomography (CT) of all patients were recorded in detail. To examine whether there is sexual transmission through vaginal from female to her partner, we employed real-time polymerase chain reaction testing (RT-PCR) to detect SARS-CoV-2 in vaginal environment (including vaginal discharge, cervical or vaginal residual exfoliated cells) and anal swab samples, and inquired recent sexual behaviors from the patients. Findings: The age range of the 35 patients with COVID-19 was 37-88 years. Over 50% patients infected with SARS-CoV-2 had chronic diseases. We tested the vaginal environment and anal swabs from the 35 female patients with COVID-19 and found that only an anal swab sample from one patient was positive for SARS-CoV-2. All the samples from vaginal environment were negative for SARS-CoV-2. The infection rate of the patients' sexual partner was 42.9%. Additionally, two female patients admitted having sex with their partners during a possible infection incubation period, while one patient's partner was uninfected and the other patient's partner was diagnosed with COVID-19 (after the diagnosis of the female patient). Conclusion: No positive RT-PCR result was found in the vaginal environment perhaps due to the lack of ACE2 expression, which is the receptor of SARS-CoV-2, in the vagina and cervix tissues (human protein atlas). The results from this study show no evidence of transmission of SARS-CoV-2 through vaginal sex from female to her partner. However, the risk of infection of non vaginal sex and other intimate contacts during vaginal sex should not be ignored.</jats:p>",2020-02-27,"['Pengfei Cui', 'Zhe Chen', 'Tian Wang', 'Jun Dai', 'Jinjin Zhang', 'Ting Ding', 'Jingjing Jiang', 'Jia Liu', 'Cong Zhang', 'Wanying Shan', 'Sheng Wang', 'Yueguang Rong', 'Jiang Chang', 'Xiaoping Miao', 'Xiangyi Ma', 'Shixuan Wang']",,,,True
15e5dd0eb126bfe384c25ba551317eb9ba2ad1ef,medrxiv,Perceptions of the Adult US Population regarding the Novel Coronavirus Outbreak,doi.org/10.1101/2020.02.26.20028308,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: COVID-19 outbreak is spreading globally. Although the risk of infection in the US is currently low, it is important to understand the public perception of risk and trust in sources of information to better inform public health messaging. In this study, we surveyed the adult US population to understand their risk perceptions about the COVID-19 outbreak.  Methods and Findings: We used an online platform to survey 718 adults in the US in early February 2020 using a questionnaire that we developed. Our sample was fairly similar to the general adult US population in terms of age, gender, race, ethnicity and education. We found that 69% of the respondents wanted the scientific/public health leadership (either the CDC Director or NIH Director) to lead the US response to COVID-19 outbreak as compared to 14% who wanted the political leadership (either the president or the Congress) to lead the response. Risk perception was low (median score of 5 out of 10) with the respondents trusting health professionals and health officials for information on COVID-19. Majority of the respondents were in favor of strict infection prevention policies to control the outbreak.  Conclusion: Given our results, the public health/scientific leadership should be at the forefront of the COVID-19 response to promote trust.</jats:p>",2020-02-27,"['SarahAnn M McFadden', 'Amyn A Malik', 'Obianuju G Aguolu', 'Kathryn S Willebrand', 'Saad B Omer']",,,,True
0fbb18050e29ca78191625d42576b1c574027377,medrxiv,Rapid Molecular Detection of SARS-CoV-2 (COVID-19) Virus RNA Using Colorimetric LAMP,doi.org/10.1101/2020.02.26.20028373,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The ability to detect an infectious agent in a widespread epidemic is crucial to the success of quarantine efforts in addition to sensitive and accurate screening of potential cases of infection from patients in a clinical setting. Enabling testing outside of sophisticated laboratories broadens the scope of control and surveillance efforts, but also requires robust and simple methods that can be used without expensive instrumentation. Here we report a method to identify SARS-CoV-2 (COVID-19) virus RNA from purified RNA or cell lysis using loop-mediated isothermal amplification (LAMP) using a visual, colorimetric detection. This test was additionally verified using RNA samples purified from respiratory swabs collected from COVID-19 patients in Wuhan, China with equivalent performance to a commercial RT-qPCR test while requiring only heating and visual inspection. This simple and sensitive method provides an opportunity to facilitate virus detection in the field without a requirement for complex diagnostic infrastructure.</jats:p>",2020-02-29,"['Yinhua Zhang', 'Nelson Odiwuor', 'Jin Xiong', 'Luo Sun', 'Raphael Ohuru Nyaruaba', 'Hongping Wei', 'Nathan A Tanner']",,,,True
4bd697fdded7ee65154e28def586a7e9b60e7078,medrxiv,Transmission characteristics of the COVID-19 outbreak in China: a study driven by data,doi.org/10.1101/2020.02.26.20028431,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The COVID-19 outbreak has been a serious public health threat worldwide. We use individually documented case descriptions of COVID-19 from China (excluding Hubei Province) to estimate the distributions of the generation time, incubation period, and periods from symptom onset to isolation and to diagnosis. The recommended 14-day quarantine period may lead to a 6.7% failure for quarantine. We recommend a 22-day quarantine period. The mean generation time is 3.3 days and the mean incubation period is 7.2 days.  It took 3.7 days to isolate and 6.6 days to diagnose a patient after his/her symptom onset. Patients may become infectious on average 3.9 days before showing major symptoms. This makes contact tracing and quarantine ineffective. The basic reproduction number is estimated to be 1.54 with contact tracing, quarantine and isolation, mostly driven by super spreaders.</jats:p>",2020-03-01,"['Meili Li', 'Pian Chen', 'Qianqian Yuan', 'Baojun Song', 'Junling Ma']",,,,True
54ae20515fcef8417e255b19df1a5bf6f2ab40bb,medrxiv,"Modelling the coronavirus disease (COVID-19) outbreak on the Diamond Princess ship using the public surveillance data from January 20 to February 20, 2020",doi.org/10.1101/2020.02.26.20028449,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The novel coronavirus disease 2019 (COVID-19) outbreak on the Diamond Princess ship has caused over 634 cases as of February 20, 2020. We model the transmission process on the ship with a stochastic model and estimate the basic reproduction number at 2.2 (95%CI: 2.1−2.4). We estimate a large dispersion parameter than other coronaviruses, which implies that the virus is difficult to go extinction. The epidemic doubling time is at 4.6 days (95%CI: 3.0−9.3), and thus timely actions were crucial. The lesson learnt on the ship is generally applicable in other settings.</jats:p>",2020-02-29,"['Shi Zhao', 'Peihua Cao', 'Daozhou Gao', 'Zian Zhuang', 'Marc Chong', 'Yongli Cai', 'Jinjun Ran', 'Kai Wang', 'Yijun Lou', 'Weiming Wang', 'Lin Yang', 'Daihai He', 'Maggie H Wang']",,,,True
e9f5957ea4b9fed303e6defc8b7f53c3e59da802,medrxiv,"The Effects of ""Fangcang, Huoshenshan, and Leishenshan"" Makeshift Hospitals and Temperature on the Mortality of COVID-19",doi.org/10.1101/2020.02.26.20028472,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background  In December 2019, a novel coronavirus disease (COVID-19) broke out in Wuhan, China, however, the factors affecting the mortality remain unclear. Methods  Thirty-two days of data that were shared by China National Health Commission and China Weather Net were collected using standard forms. The difference in the mortality of confirmed and severe cases before and after the use of Fangcang, Huoshenshan, and Leishenshan makeshift hospitals (MSHs) was tested using Mann-Whitney U test. We also studied whether air temperature (AT) could affect the above outcomes of COVID-19 cases by performing Spearman analysis. Results The mortality of confirmed cases was significantly decreased both in Wuhan (U = 1, P &lt; 0.001) and Hubei (U = 0, P &lt; 0.001), while in non-Hubei regions, as a contrast, the mortality of confirmed cases remained unchanged (U = 40, P = 0.139). However, another eight days later, changes in the mortality in non-Hubei regions also became significant (U = 73, P = 0.039). Mortality of confirmed cases was found to be significantly correlated with temperature both in Wuhan (r = -0.441, P = 0.012) and Hubei (r = -0.440, P = 0.012). Conclusions Our findings indicated that both the use of MSHs and the rise of AT were beneficial to the survival of COVID-19 cases.</jats:p>",2020-02-29,"['Yuwen Cai', 'Tianlun Huang', 'Xin Liu', 'Gaosi Xu']",,,,False
691da9d5576aa959e22114a1ebb35548efd276a0,medrxiv,Infection Dynamics of Coronavirus Disease 2019 (Covid-19) Modeled with the Integration of the Eyring Rate Process Theory and Free Volume Concept,doi.org/10.1101/2020.02.26.20028571,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The Eyrings rate process theory and free volume concept, two very popular theories in chemistry and physics fields, are employed to treat infectious disease transmissions. The susceptible individ- uals are assumed to move stochastically from one place to another. The virus particle transmission rate is assumed to obey the Eyring rate process theory and also controlled by how much free volume available in a system. The transmission process is considered to be a sequential chemical reaction, and the concentrations or fractions of four epidemiological compartments, the susceptible, the exposed, the infected, and the removed, can be derived and calculated. The obtained equations show that the basic reproduction number, R0, is not a constant, dependent on the volume frac- tion of virus particles, virus particle size, and virus particle packing structure, the energy barrier associated with susceptible individuals, and environment temperature. The developed models are applied to treat coronavirus disease 2019 (Covid-19) transmission and make predictions on peak time, peak infected, and R0. Our work provides a simple and straightforward approach to estimate how infection diseases evolve and how many people may be infected.</jats:p>",2020-02-29,['Tian Hao'],,,,True
e848fdc93f0a0268bb9124b00adf7acae010f8d7,medrxiv,Heart injury signs are associated with higher and earlier mortality in coronavirus disease 2019 (COVID-19),doi.org/10.1101/2020.02.26.20028589,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Importance: Heart injury can be easily induced by viral infection such as adenovirus and enterovirus. However, whether coronavirus disease 2019 (COVID-19) causes heart injury and hereby impacts mortality has not yet been fully evaluated. Objective: To explore whether heart injury occurs in COVID-19 on admission and hereby aggravates mortality later. Design, Setting, and Participants A single-center retrospective cohort study including 188 COVID-19 patients admitted from December 25, 2019 to January 27, 2020 in Wuhan Jinyintan Hospital, China; follow up was completed on February 11, 2020. Exposures:  High levels of heart injury indicators on admission (hs-TNI; CK; CK-MB; LDH; α-HBDH). Main Outcomes and Measures: Mortality in hospital and days from admission to mortality (survival days). Results: Of 188 patients with COVID-19, the mean age was 51.9 years (standard deviation: 14.26; range: 21~83 years) and 119 (63.3%) were male. Increased hs-TnI levels on admission tended to occur in older patients and patients with comorbidity (especially hypertension). High hs-TnI on admission (≥ 6.126 pg/mL), even within the clinical normal range (0~28 pg/mL), already can be associated with higher mortality. High hs-TnI was associated with increased inflammatory levels (neutrophils, IL-6, CRP, and PCT) and decreased immune levels (lymphocytes, monocytes, and CD4+ and CD8+ T cells). CK was not associated with mortality. Increased CK-MB levels tended to occur in male patients and patients with current smoking. High CK-MB on admission was associated with higher mortality. High CK-MB was associated with increased inflammatory levels and decreased lymphocytes. Increased LDH and α-HBDH levels tended to occur in older patients and patients with hypertension. Both high LDH and α-HBDH on admission were associated with higher mortality. Both high LDH and α-HBDH were associated with increased inflammatory levels and decreased immune levels. hs-TNI level on admission was negatively correlated with survival days (r= -0.42, 95% CI= -0.64~-0.12, P=0.005). LDH level on admission was negatively correlated with survival days (r= -0.35, 95% CI= -0.59~-0.05, P=0.022). Conclusions and Relevance: Heart injury signs arise in COVID-19, especially in older patients, patients with hypertension and male patients with current smoking. COVID-19 virus might attack heart via inducing inflammatory storm. High levels of heart injury indicators on admission are associated with higher mortality and shorter survival days. COVID-19 patients with signs of heart injury on admission must be early identified and carefully managed by cardiologists, because COVID-19 is never just confined to respiratory injury.</jats:p>",2020-02-29,"['Chaomin Wu', 'Xianglin Hu', 'Jianxin Song', 'Chunling Du', 'Jie Xu', 'Dong Yang', 'Dechang Chen', 'Ming Zhong', 'Jinjun Jiang', 'Weining Xiong', 'Ke Lang', 'Yuye Zhang', 'Guohua Shi', 'Lei Xu', 'Yuanlin Song', 'Xin Zhou', 'Ming Wei', 'Junhua Zheng']",,,,False
ae61300f4e7a12a68baf114f199eb51940c7aad3,medrxiv,Prediction of the Epidemic of COVID-19 Based on Quarantined Surveillance in China,doi.org/10.1101/2020.02.27.20027169,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background and Objective: To predict the epidemic of COVID-19 based on quarantined surveillance from real world in China by modified SEIR model different from the previous simply mathematical model. Design and Methods: We forecasted the epidemic of COVID-19 based on current clinical and epidemiological data and built a modified SEIR model to consider both the infectivity during incubation period and the influence on the epidemic from strict quarantined measures. Results: The peak time of the curve for the infected newly diagnosed as COVID-19 should substantially present on Feb.5,2020(in non-Hubei areas) and Feb.19,2020(in Hubei. It is estimated that the peak of the curve of the cumulative confirmed cases will appear in non-Hubei areas on Mar.3,2020 and in Hubei province on Mar.10,2020,and the total number of the patients diagnosed as COVID-19 is 18,000 in non-Hubei areas and 78,000-96,000 in Hubei.The Chinese COVID-19 epidemic can be completely controlled in May,2020. Conclusions: COVID-19 is only a local outbreak in Hubei Province,China.It can be probably avoided the pandemic of global SARS-CoV-2 cases rise with the great efforts by Chinese government and its people.</jats:p>",2020-02-29,"['Rui Li', 'Wenliang Lu', 'Xifei Yang', 'Peihua Feng', 'Ozarina Muqimova', 'Xiaoping Chen', 'Gang Wei']",,,,True
2e41aee6651cf4cab4edf5aa67cc401c2bef9d67,medrxiv,Sex differences in clinical findings among patients with coronavirus disease 2019 (COVID-19) and severe condition,doi.org/10.1101/2020.02.27.20027524,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: To compare the sex differences in the clinical findings among patients with severe coronavirus disease 2019 (COVID-19). Methods: We retrospectively collected data of 47 patients diagnosed as severe type of COVID-19 from February 8 to 22, 2020, including demographics, illness history, physical examination, laboratory test, management, and compared differences between men and women. Results: Of the 47 patients, 28 (59.6%) were men. The median age was 62 years, and 30 (63.8%) had comorbidities. The initial symptoms were mainly fever (34 [72.3%]), cough (36 [76.6%]), myalgia (5 [10.6%]) and fatigue (7 [14.9%]). Procalcitonin level was higher in men than in women (0.08 vs. 0.04ng/ml, p=0.002). N-terminal-pro brain natriuretic peptide increased in 16 (57.1%) men and 5 (26.3%) women (p=0.037). Five men (17.9%) had detected positive influenza A antibody, but no women. During 2-week admission, 5 (17.9%) men and 1 (5.3%) woman were reclassified into the critical type due to deterioration. Mortality was 3.6% in men and 0 in women respectively. Four (21.1%) women and one man (3.6%) recovered and discharged from hospital. Conclusion: Sex differences may exist in COVID-19 patients of severe type. Men are likely to have more complicated clinical condition and worse in-hospital outcomes as compared to women.</jats:p>",2020-02-29,"['Jing Li', 'Yinghua Zhang', 'Fang Wang', 'Bing Liu', 'Hui Li', 'Guodong Tang', 'Zhigang Chang', 'Aihua Liu', 'Chunyi Fu', 'Jing Gao', 'Jing Li']",,,,True
2d0285c90976dfa43d58eca6b7d1d7ef29994fc2,medrxiv,Therapeutic effects of dipyridamole on COVID-19 patients with coagulation dysfunction,doi.org/10.1101/2020.02.27.20027557,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The human coronavirus HCoV-19 infection can cause acute respiratory distress syndrome (ARDS), hypercoagulability, hypertension, extrapulmonary multiorgan dysfunction. Effective antiviral and anti-coagulation agents with safe clinical profiles are urgently needed to improve the overall prognosis. We screened an FDA approved drug library and found that an anticoagulant agent dipyridamole (DIP) suppressed HCoV-19 replication at an EC50 of 100 nM in vitro. It also elicited potent type I interferon responses and ameliorated lung pathology in a viral pneumonia model. In analysis of twelve HCoV-19 infected patients with prophylactic anti-coagulation therapy, we found that DIP supplementation was associated with significantly increased platelet and lymphocyte counts and decreased D-dimer levels in comparison to control patients. Two weeks after initiation of DIP treatment, 3 of the 6 severe cases (60%) and all 4 of the mild cases (100%) were discharged from the hospital. One critically ill patient with extremely high levels of D-dimer and lymphopenia at the time of receiving DIP passed away. All other patients were in clinical remission. In summary, HCoV-19 infected patients could potentially benefit from DIP adjunctive therapy by reducing viral replication, suppressing hypercoagulability and enhancing immune recovery. Larger scale clinical trials of DIP are needed to validate these therapeutic effects.</jats:p>",2020-02-29,"['Xiaoyan Liu', 'Zhe Li', 'Shuai Liu', 'Zhanghua Chen', 'Zhiyao Zhao', 'Yi-you Huang', 'Qingling Zhang', 'Jun Wang', 'Yinyi Shi', 'Yanhui Xu', 'Jing Sun', 'Huifang Xian', 'Rongli Fang', 'Fan Bai', 'Changxing Ou', 'Bei Xiong', 'Andrew M Lew', 'Jun Cui', 'Hui Huang', 'Jincun Zhao', 'Xuechuan Hong', 'Yuxia Zhang', 'Fulin Zhou', 'Hai-Bin Luo']",,,,True
b38f3c83aaa3fa7c8f5c87af266793afcbd11c86,medrxiv,Prediction of criticality in patients with severe Covid-19 infection using three clinical features: a machine learning-based prognostic model with clinical data in Wuhan,doi.org/10.1101/2020.02.27.20028027,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background:  COVID-19 appeared in Wuhan, China in December 2019, and since then it has immediately become a serious public health problem worldwide. No specific medicine against COVID-19 has been found until now. However, mortality risk in patients could potentially be predicted before they transmit to critically ill.  Methods:  We screened the electronic records of 2,799 patients admitted in Tongji Hospital from January 10th to February 18th, 2020. There were 375 discharged patients including 201 survivors. We built a prognostic prediction model based on XGBoost machine learning algorithm and then tested 29 patients (included 3 patients from other hospital) who were cleared after February 19th.   Results: The mean age of the 375 patients was 58.83 years old with 58.7% of males. Fever was the most common initial symptom (49.9%), followed by cough (13.9%), fatigue (3.7%), and dyspnea (2.1%). Our model identified three key clinical features, i.e., lactic dehydrogenase (LDH), lymphocyte and High-sensitivity C-reactive protein (hs-CRP), from a pool of more than 300 features. The clinical route is simple to check and can precisely and quickly assess the risk of death. Therefore, it is of great clinical significance.  Conclusion: The three indices-based prognostic prediction model we built is able to predict the mortality risk, and present a clinical route to the recognition of critical cases from severe cases. It can help doctors with early identification and intervention, thus potentially reducing mortality.</jats:p>",2020-03-01,"['Li Yan', 'Hai-Tao Zhang', 'Yang Xiao', 'Maolin Wang', 'Chuan Sun', 'Jing Liang', 'Shusheng Li', 'Mingyang Zhang', 'Yuqi Guo', 'Ying Xiao', 'Xiuchuan Tang', 'Haosen Cao', 'Xi Tan', 'Niannian Huang', 'Bo Jiao', 'Ailin Luo', 'Zhiguo Cao', 'Hui Xu', 'Ye Yuan']",,,,True
264a816e7099246c13a5dad3a581a474d85d50bd,medrxiv,Hypokalemia and Clinical Implications in Patients with Coronavirus Disease 2019 (COVID-19),doi.org/10.1101/2020.02.27.20028530,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>BACKGROUND: SARS-CoV-2 has caused a series of COVID-19 globally. SARS-CoV-2 binds angiotensin I converting enzyme 2 (ACE2) of renin-angiotensin system (RAS) and causes prevalent hypokalemia METHODS: The patients with COVID-19 were classified into severe hypokalemia, hypokalemia, and normokalemia group. The study aimed to determine the relationship between hypokalemia and clinical features, the underlying causes and clinical implications of hypokalemia.  RESULTS: By Feb 15, 2020, 175 patients with COVID-19 (92 women and 83 men; median age, 46 [IQR, 34-54] years) were admitted to hospital in Wenzhou, China, consisting 39 severe hypokalemia-, 69 hypokalemia-, and 67 normokalemia patients.  Gastrointestinal symptoms were not associated with hypokalemia among 108 hypokalemia patients (P&gt;0.05).  Body temperature, CK, CK-MB, LDH, and CRP were significantly associated with the severity of hypokalemia (P&lt;0.01). 93% of severe and critically ill patients had hypokalemia which was most common among elevated CK, CK-MB, LDH, and CRP. Urine K+ loss was the primary cause of hypokalemia.  severe hypokalemia patients was given 3 g/day, adding up to an average of 34 (SD=4) g potassium during hospital stay. The exciting finding was that patients responded well to K+ supplements when they were inclined to recovery.  CONCLUSIONS: Hypokalemia is prevailing in patients with COVID-19. The correction of hypokalemia is challenging because of continuous renal K+ loss resulting from the degradation of ACE2. The end of urine K+ loss indicates a good prognosis and may be a reliable, in-time, and sensitive biomarker directly reflecting the end of adverse effect on RAS system.</jats:p>",2020-02-29,"['dong chen', 'Xiaokuni Li', 'qifa song', 'Chenchan Hu', 'Feifei Su', 'Jianyi Dai']",,,,True
75e68869f9b65bca661e768402395d9dede6de2c,medrxiv,Modeling the Epidemic Dynamics and Control of COVID-19 Outbreak in China,doi.org/10.1101/2020.02.27.20028639,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The coronavirus disease 2019 (COVID-19) is rapidly spreading over China and more than 30 countries in last two months. COVID-19 has multiple characteristics distinct from other infectious diseases, including a high infectivity during incubation, time delay between real dynamics and daily observed case numbers, and the effects from multiple quarantine and control measures. We develop a model SUQC to adequately characterizes the dynamics of COVID-19 and explicitly model the control by artificial measures, which is more suitable for analysis than other existing epidemic models.  The SUQC model is applied to the daily released data of the confirmed infected to analyze the outbreak of COVID-19 in Wuhan, Hubei (excluding Wuhan), China (excluding Hubei) and four first-tier cities of China. We find that, before January 30, 2020, all these regions except Beijing have a reproductive number R&gt;1, and after January 30, all regions have a reproductive number R&lt;1, indicating the effectiveness of the quarantine and control measures in inhibiting COVID-19. The confirmation rate of Wuhan is 0.0643, significantly lower than 0.1914 of Hubei (excluding Wuhan) and 0.2189 of China (excluding Hubei), but increases to 0.3229 after Feb 12th when clinical diagnosis was adopted. The un-quarantined infected individuals in Wuhan on February 12, 2020 is as high as 3,509 and decreases to 334 on February 21th, 2020.   After fitting the model with recent data, we predict that the end times of COVID-19 of Wuhan and Hubei are around late-March, of China (excluding Hubei) around mid-March, and of the four tier-one cities before March 2020. A total of 80,511 individuals of the whole country are infected, among which 49,510 are from Wuhan, 17,679 from Hubei(excluding Wuhan), and the rest 13,322 from other regions of China (excluding Hubei). We suggest the rigorous quarantine and control measures should be kept before March in Beijing, Shanghai, Guangzhou and Shenzhen, and before late-March in Hubei. The model can also be useful to predict the trend of epidemic and provide quantitative guide for other counties in a high risk of outbreak, such as South Korea, Japan and Iran.</jats:p>",2020-02-29,"['Shilei Zhao', 'Hua Chen']",,,,True
b579c3547bba2a33057373d57b7c05f37dd4cfc3,medrxiv,Evaluation of Enzyme-Linked Immunoassay and Colloidal Gold- Immunochromatographic Assay Kit for Detection of Novel Coronavirus (SARS-Cov-2) Causing an Outbreak of Pneumonia (COVID-19),doi.org/10.1101/2020.02.27.20028787,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Abstract  BACKGROUND: In December 2019, a novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19) occurred in Wuhan, China. Travel-associated cases have also been reported in other countries. The number of cases has increased rapidly but laboratory diagnosis is limited.  METHODS: We collect two groups of cases diagnosed with COVID-19 for experiments. One group collected 63 samples for Enzyme-linked immunosorbent assay (ELISA) IgG and IgM antibodies. The other group collected 91 plasma samples for colloidal gold-immunochromatographic assay (GICA). RESULTS: The sensitivity of the combined ELISA IgM and ELISA IgG detection was 55/63 ( 87.3%), The sensitivity of the combined GICA IgM and GICA IgG detection was 75/91 ( 82.4%), Both methods are negative for healthy controls, specificity of 100% .There is no significant difference between the sensitivity of between ELISA and GICA (IgM+ IgG).  CONCLUSIONS: ELISA and GICA for specific IgM and IgG antibodies are conventional serological assays, they are simple, fast, and safe, the results can be used for clinical reference, and the huge clinical diagnosis and treatment pressure can be greatly relieved.</jats:p>",2020-03-01,"['Jie Xiang', 'Mingzhe Yan', 'Hongze Li', 'Ting Liu', 'Chenyao Lin', 'Shuang Huang', 'Changxin Shen']",,,,True
905603e9db862f9b4b42a95f51e9c8d0015d1dff,medrxiv,Transmission potential of COVID-19 in South Korea,doi.org/10.1101/2020.02.27.20028829,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Since the first identified individual of 2019 novel coronavirus (COVID-19) infection on Jan 20, 2020 in South Korea, the number of confirmed cases rapidly increased. As of Feb 26, 2020, 1,261 cases of COVID-19 including 12 deaths were confirmed in South Korea. Using the incidence data of COVID-19, we estimate the reproduction number at 1.5 (95% CI: 1.4-1.6), which indicates sustained transmission and support the implementation of social distancing measures to rapidly control the outbreak.</jats:p>",2020-02-29,"['Eunha Shim', 'Amna Tariq', 'Wongyeong Choi', 'Yiseul Lee', 'Gerardo Chowell']",,,,True
79c090e38059cec90bb7321090185c603e24cbc2,medrxiv,A simple ecological model captures the transmission pattern of the coronavirus COVID-19 outbreak in China,doi.org/10.1101/2020.02.27.20028928,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The rapid spread of the 2019 novel coronavirus (COVID-19), initially reported in the city of Wuhan in China, and quickly transmitted to the entire nation and beyond, has become an international public health emergency. Estimating the final number of infection cases and the turning point (time with the fastest spreading rate) is crucial to assessing and improving the national and international control measures currently being applied. In this paper we develop a simple model based on infectious growth with a time-varying infection rate, and estimate the final number of infections and the turning point using data updated daily from 3 February 2020, when China escalated its initial public health measures, to 10 February. Our model provides an extremely good fit to the existing data and therefore a reasonable estimate of the time-varying infection rate that has largely captured the transmission pattern of this epidemic outbreak. Our estimation suggests that (i) the final number of infections in China could reach 78,000 with an upper 95% confidence limit of 88,880; (ii) the turning point of the fastest spread was on the 4th or the 5th of February; and (iii) the projected period for the end of the outbreak (i.e., when 95% of the final predicted number of infection is reached) will be the 24th of February, with an upper 95% confidence limit on the 19th of March. This suggests that the current control measures in China are excellent, and more than sufficient to contain the spread of this highly infectious novel coronavirus, and that the application of such measures could be considered internationally for the global control of this outbreak.</jats:p>",2020-02-29,"['Feng Zhang', 'Jinmei Zhang', 'Menglan Cao', 'Cang Hui']",,,,False
68ed7bb581b0cf32116ee46767c08e3180b05c34,medrxiv,"Clinical characteristics of 36 non-survivors with COVID-19 in Wuhan, China",doi.org/10.1101/2020.02.27.20029009,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background Although the outbreak of Coronavirus disease 2019 (COVID-19) has caused over 2200 deaths in China, there was no study about death yet. We aimed to describe the clinical characteristics of non-survivors with COVID-19. Methods For this retrospective, single-center study, we included 36 non-survivors with COVID-19 in the Fifth Hospital of Wuhan. Cases were confirmed by real-time RT-PCR between Jan 21 and Feb 10, 2020 according to the recommended protocol. The epidemiological, demographic, clinical, laboratory, radiological and treatment data were collected and analyzed. Outcomes were followed up until Feb 14, 2020. This study was approved by the ethics commissions of the Fifth Hospital of Wuhan, with a waiver of informed consent due to a public health outbreak investigation.  Results We included 36 patients who died from COVID-19. The mean age of the patients was 69.22 years (SD 9.64, range 50-90). 25(69.44%) patients were males, and 11 (30.56%) female. 26 (72.22%) patients had chronic diseases, mainly including hypertension, cardiovascular disease and diabetes. Patients had common clinical symptoms of fever (34 [94.44%] patients), cough (28 [77.78%] patients), shortness of breath (21 [58.33%] patients), and fatigue (17 [47.22%] patient). Chest computed tomographic scans showed that 31 (96.88%) patients had bilateral pneumonia. Lymphopenia occurred in 24 patients (70.59%), decreased albumin (30.18, [SD, 4.76]) in 25 patients (80.65%), elevated D-dimer (8.64 [IQR, 2.39-20]) in 27 patients (100%), and elevated lactate dehydrogenase (502.5 U/L [IQR, 410-629]) in 26 patients (100%). Nearly all of the patients have elevated CRP (106.3 mg/L [IQR, 60.83-225.3]), PCT (0.61 ng/ml [IQR, 0.16-2.10]) and IL-6 (100.6 pg/ml [IQR, 51.51-919.5]). Most patients received antiviral therapy and antibiotic therapy, and more than half of patients received glucocorticoid therapy (25 [69.44%]). All the patients had acute respiratory distress syndrome (ARDS). The median time from onset to ARDS was 11 days.  One (2.78%) patient presented with acute renal injury. The median time from onset to death was 17 days. Interpretation Lots of patients died from COVID-19 till now. The median survival time of these non-survivors from onset to death was about 2 weeks. Most patients were older males with comorbidities. They finally progressed to ARDS. The median time from onset to ARDS was 11 days. Gradually decreased lymphocytes and increased inflammation biomarkers were common, and need to be monitored in the routine treatment.</jats:p>",2020-02-29,"['Ying Huang', 'Rui Yang', 'Ying Xu', 'Ping Gong']",,,,True
24e17488d399c436305c819953beae2961214771,medrxiv,"Epidemiological and clinical features of COVID-19 patients with and without pneumonia in Beijing, China",doi.org/10.1101/2020.02.28.20028068,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background:SARS-CoV-2-caused coronavirus disease (COVID-19) is posinga large casualty. The features of COVID-19patients withand without pneumonia,SARS-CoV-2 transmissibility in asymptomatic carriers, and factors predicting disease progression remain unknown.  Methods: We collected information on clinical characteristics, exposure history, andlaboratory examinations of all laboratory-confirmed COVID-19 patients admitted to PLA General Hospital. Cox regression analysis was applied to identify prognostic factors. The last follow-up was February 18, 2020. Results:We characterized 55 consecutive COVID-19 patients. The mean incubation was 8.42(95% confidence interval [CI], 6.55-10.29) days. The mean SARS-CoV-2-positive duration from first positive test to clearance was 9.71(95%CI, 8.21-11.22) days. COVID-19 course was approximately 2 weeks. Asymptomatic carriers might transmit SARS-CoV-2. Compared with patients without pneumonia, those with pneumonia were 15 years older and had a higher rate of hypertension, higher frequencies of having a fever and cough, and higher levels of interleukin-6 (14.61 vs. 8.06pg/mL, P=0.040), B lymphocyte proportion (13.0% vs.10.0%, P=0.024), low account (&lt;190/μL) of CD8+ T cells (33.3% vs. 0, P=0.019). Multivariate Cox regression analysis indicated that circulating interleukin-6 andlactate independently predicted COVID-19 progression, with a hazard ratio (95%CI) of 1.052 (1.000-1.107) and 1.082 (1.013-1.155), respectively. During disease course,T lymphocytes were generally lower,neutrophils higher, in pneumonia patients than in pneumonia-free patients. CD8+ lymphocytes did not increase at the 20th days after illness onset. Conclusion: The epidemiological features areimportant for COVID-19 prophylaxis. Circulating interleukin-6 and lactateare independent prognostic factors. CD8+ T cell exhaustion might be critical in the development of COVID-19.</jats:p>",2020-03-03,"['Penghui Yang', 'Yibo Ding', 'Zhe Xu', 'Rui Pu', 'Ping Li', 'Jin Yan', 'Jiluo Liu', 'Fanping Meng', 'Lei Huang', 'Lei Shi', 'Tianjun Jiang', 'Enqiang Qin', 'Min Zhao', 'Dawei Zhang', 'Peng Zhao', 'Lingxiang Yu', 'Zhaohai Wang', 'Zhixian Hong', 'Zhaohui Xiao', 'Qing Xi', 'Dexi Zhao', 'Peng Yu', 'Caizhong Zhu', 'Zhu Chen', 'Shaogeng Zhang', 'Junsheng Ji', 'Guangwen Cao', 'Fusheng Wang']",,,,True
54cfc3c68e1e4832fee5b3294e5673e37978ebdf,medrxiv,Risk factors related to hepatic injury in patients with corona virus disease 2019,doi.org/10.1101/2020.02.28.20028514,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Aims: Corona virus disease 2019 (COVID-19) has rapidly become the most severe public health issue all over the world. Despite respiratory symptoms, hepatic injury has also been observed in clinical settings. This study aimed to investigate the risk factors involved with hepatic injury in the patients with COVID-19. Methods: A total of 85 hospitalized patients who were diagnosed with COVID-19 in Beijing Youan Hospital were retrospectively analyzed. According to liver function, they were divided into ALT normal group (n=52) and ALT elevation group (n=33). Clinical features and laboratory data were compared between the two groups. The independent risk factors for liver injury were analyzed. Results: There were 33 patients with hepatic injury in our study, accounting for 38.8% (33/85). The patients in ALT elevation group were older than those in ALT normal group. The levels of lactic acid, CRP, myoglobin, and neutrophils were significantly higher in ALT elevation group. The lymphocytes and albumin were significantly lower in ALT elevation group. The proportion of severe and critical patients in ALT elevation group was significantly higher. Multivariate logistic regression analysis showed CRP ≥20 mg/L and lymphocyte count&lt; 1.1*10^9/L were independently related to hepatic injury. Conclusions: Lymphopenia and CRP may serve as the risk factors related to hepatic injury in patients with COVID-19, which might be related to inflammatory cytokine storm in liver injury. Early detection and timely treatment of hepatic injury in patients with COVID-19 are necessary.</jats:p>",2020-03-03,"['Lu Li', 'Shuang Li', 'Manman Xu', 'Pengfei Yu', 'Sujun Zheng', 'Zhongping Duan', 'Jing Liu', 'Yu Chen', 'Junfeng Li']",,,,True
d75c48f51b2a5c26a41fe615339e5947d5e9cb30,medrxiv,Analysis of epidemiological characteristics of coronavirus 2019 infection and preventive measures in Shenzhen China: a heavy population city,doi.org/10.1101/2020.02.28.20028555,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Coronavirus 2019 infection (COVID-19) outbroke in Wuhan, Hubei and spread to all provinces in China and other countries. Shenzhen ranked the top cities outside Wuhan with reported 416 confirmed cases by February 20, 2020. Here, we analyzed the epidemiological characteristics of COVID-19 in Shenzhen and potential link to the preventive strategies for the whole city and inside hospitals.  Based on the daily new cases, the epidemic of COVID-19 in Shenzhen can be classified into three phases: the slow increase phase from January 19 to January 28, the rapid increase and plateau phase from January 29 to February 5 and the decline phase since February 6. In the three phases, the number of patients from Hubei decreased, and the number of familial clustering cases increased. The newly diagnosed COVID-19 cases reached its peak around January 31, which was 7 days after the peak date of cases arrival at Shenzhen. A series of early preventive strategies were implemented since January 19, which included detection of body temperature at all entrances of main traffic and buildings, outpatients service specially for patients with fever in all main hospitals in Shenzhen. All the patients with fever were screened with nasal or throat swab PCR detection of coronavirus 2019, Chest CT and blood lymphocyte counting in order to find out early case of COVID-19. Observation wards were established in every main hospital and a designated hospital was responsible for admission and medical care of all confirmed cases. Protection procedure was established for all medical staff involved in the screening and care of suspected and confirmed cases. 14 days isolated observation of all subjects arrived at Shenzhen from Hubei was implemented in February 2. After the implementation of all these strategies and measures, the COVID-19 cases started to decline since February 6. There were almost no community transmission and nosocomial infection occurred in Shenzhen. In conclusion, in situation of major outbreak of respiratory infectious disease, such as COVID-19, in nearby province of Hubei, Shenzhen, a high population density, high proportion of external population and high mobility city, has to face the imported cases and risk of spreading the outbreak into Shenzhen city. The implementation of early preventive strategies and measures in Shenzhen were successful in early identification of COVID-19 cases and prevented major outbreak occurred in Shenzhen. Early identification of imported cases, prevention of family clustering transmission, preventive measures in the public area and very strict infection control procedure in hospital setting are crucial for the successful control of outbreak in Shenzhen.</jats:p>",2020-03-03,"['Kai Yang', 'Lingwei Wang', 'Furong Li', 'Dandan Chen', 'Xi Li', 'Chen Qiu', 'Rongchang Chen']",,,,True
94284e14b36025dc9c7072dc90dfd8c72dc429ad,medrxiv,Clinical significance of IgM and IgG test for diagnosis of highly suspected COVID-19 infection,doi.org/10.1101/2020.02.28.20029025,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Quick, simple and accurate diagnosis of suspected COVID-19 is very important for the screening and therapy of patients. Although several methods were performed in clinical practice, however, the IgM and IgG diagnostic value evaluation was little performed. 57 suspected COVID-19 infection patients were enrolled in our study. 24 patients with positive and 33 patients with negative nucleic acid test. The positive rate of COVID-19 nucleic acid was 42.10%. The positive detection rate of combination of IgM and IgG for patients with COVID-19 negative and positive nucleic acid test was 72.73% and 87.50%. The results were significantly higher than the nucleic acid or IgM, IgG single detection. hsCRP in the COVID-19 nucleic acid negative group showed significantly higher than the positive groups (P=0.0298). AST in the COVID-19 IgM negative group showed significantly lower than the positive groups (P=0.0365). We suggest a quick, simple, accurate aided detection method for the suspected patients and on-site screening in close contact with the population.</jats:p>",2020-03-03,"['Xingwang Jia', 'Pengjun Zhang', 'Yaping Tian', 'Junli Wang', 'Huadong Zeng', 'Jun Wang', 'Liu Jiao', 'Zeyan Chen', 'Lijun Zhang', 'Haihong He', 'Kunlun He', 'Yajie Liu']",,,,True
a5039336577ac0fed15b784adb912df2a6a143f3,medrxiv,Analysis on the Clinical Characteristics of 36 Cases of Novel Coronavirus Pneumonia in Kunming,doi.org/10.1101/2020.02.28.20029173,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: To analyze the clinical characteristics of patients with novel coronavirus pneumonia in Kunming City, and to study the correlation between nutritional status and immune function. Methods: Clinical data of 36 patients with novel coronavirus pneumonia in isolation area of Kunming Third People's Hospital from January 31 to February 15, 2020 were collected, and the basic situation, clinical characteristics, laboratory examination and CT imaging characteristics were analyzed. Serum albumin (ALB), prealbumin (PAB), hypersensitive c-reactive protein (hs-crp), CD3T cells, CD4T cells, CD8T cells and normal control group were analyzed. A simple linear regression analysis of the relationship between proalbumin and T cell subpopulation counts in the blood of patients.  Results: (1) The patients with new coronavirus pneumonia in Kunming were mainly of common type. (2) 50% of the patients' first symptoms were fever and cough; (3) The total number of white blood cells in peripheral blood was normal or decreased in 23 cases (79%), and the lymphocyte count decreased in 5 cases (13.89%), without anemia. Hypersensitive c-reactive protein increased in 19 (52.78%) cases, and procalcitonin increased in 1 case. Albumin decreased in 5 cases (13.89%), proalbumin decreased in 15 cases (41.67%), alanine transaminase increased slightly in 4 cases (11.11%), alanine transaminase increased slightly in 4 cases (11.11%), total bilirubin increased slightly in 11 cases (30.56%), and renal function and blood coagulation were normal. Absolute value of CD3+T cells is with a decrease in 21 cases (58.3%), CD4+T in 28 cases (77.8%), CD8+T in 17 cases (47.2%), and CD4+/ CD8+ inverse in 6 cases (16.7%). (4) The prealbumin, CD3 T cells, CD4 T cells and CD8 T cells in the new coronavirus pneumonia group were significantly lower than those in the normal control group, and the hypersensitive c-reactive protein was higher than that in the normal control group. (5) The levels of PAB in the serum of the patients were linearly correlated with hs-crp, CD3 T cells, CD4 T cells and CD8 T cells, and the correlation coefficients were -0.474, 0.558, 0.467 and 0.613, respectively, showing statistical differences.  Conclusion: The clinical characteristics of the novel coronavirus pneumonia in Kunming are different from those in Wuhan. The changes of serum proalbumin and T cell subsets are relatively obvious. Changes in serum proalbumin may contribute to the early warning of novel coronavirus pneumonia. The nutritional status of patients with common and mild pneumonia should be considered.</jats:p>",2020-03-01,"['Haiyan Fu', 'Hongjuan Li', 'Xiaoqing Tang', 'Xiang Li', 'Jie Shen', 'Yujun Zhou', 'Bing Xu', 'Yu Luo']",,,,True
2af91bbb625d983d5ad3aadb9e5f1d82268a0f1f,medrxiv,Highly ACE2 Expression in Pancreas May Cause Pancreas Damage After SARS-CoV-2 Infection,doi.org/10.1101/2020.02.28.20029181,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The ongoing outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in the end of 2019 in China has triggered a global public health crisis. Previous studies have shown that SARS-CoV-2 infects cells by binding angiotensin-converting enzyme 2 (ACE2), which is the same as SARS-CoV. The expression and distribution of ACE2 in the pancreas are unknown. At the same time, the injury of pancreas after SARS-CoV-2 infection has not been concerned. Here, we collected public datasets (bulk RNA-seq and single-cell RNA-seq) to indicate the expression and the distribution of ACE2 in pancreas (in both exocrine glands and islets). And further, clinical data including mild and severe patients with COVID-19 demonstrated there existed mild pancreatitis. In the 67 severe cases, 11 patients (16.41%) showed elevated levels of both amylase and lipase, and 5 patients (7.46%) showed imaging alterations. Only one patient (1.85%) showed elevated levels of both amylase and lipase in 54 mild cases, without imaging changes. Our study revealed the phenomenon and possible cause of mild pancreatic injury in patients with COVID-19. This suggests that pancreatitis after SARS-CoV-2 infection should also be paid attention in clinical work.</jats:p>",2020-03-03,"['Furong Liu', 'Xin Long', 'Wenbin Zou', 'Minghao Fang', 'Wenjuan Wu', 'Wei Li', 'Bixiang Zhang', 'Wanguang Zhang', 'Xiaoping Chen', 'Zhanguo Zhang']",,,,True
530f3ba1a2c044305d73123fd8d2246f63120bc3,medrxiv,The Impact of the COVID-19 Outbreak on the Medical Treatment of Chinese Children with Chronic Kidney Disease (CKD)：A Multicenter Cross-section Study in the Context of a Public Health Emergency of International Concern,doi.org/10.1101/2020.02.28.20029199,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: To investigate the impact of the COVID-19 outbreak on the medical advice seeking of Chinese children with chronic kidney disease (CKD).  Materials and Methods: An anonymous online questionnaire survey was conducted in 17 pediatric nephropathy diagnosis and treatment centers in China. The questions collected basic information on the patients and their parents and data on changes in the approach to medical treatment and their needs in the context of the outbreak etc. This is a Multicenter Cross-section Study. Results: A total of 735 valid questionnaires were collected. 555 patients (75.5%) and their parents said that the outbreak had a significant influence on their medical treatment: 264 patients (47.6%) said that it would be delayed by 2 to 4 weeks and 199 patients (35.9%) by 4 to 8 weeks. 510 patients (84.16%) hoped to get in touch with specialists through online consultation, and 528 patients (84.5%) hoped that online consultation could be implemented and that medication could be delivered to them.. A total of 458 patients (62.3%) said that their greatest concern was that the CKD would be aggravated or that they would experience a relapse; only 203 patients were infected by 2019-nCoV. A total of 313 patients (42.5%) experienced anxiety and thus required the intervention of psychologists. Conclusion: The COVID-19 outbreak has affected the medical treatment of children with CKD. Online consultation, medication delivery and psychological counselling are the greatest needs reported by patients and their families and could especially provide solutions for the management of low income children with CKD in remote rural areas in the context of the COVID-19 epidemic.</jats:p>",2020-03-03,"['Gaofu Zhang', 'Haiping Yang', 'Aihua Zhang', 'Qian Shen', 'Li Wang', 'Zhijuan Li', 'Yuhong Li', 'Lijun Zhao', 'Yue Du', 'Liangzhong Sun', 'Bo Zhao', 'Hongtao Zhu', 'Haidong Fu', 'Xiaoyan Li', 'Xiaojie Gao', 'Sheng Hao', 'Juanjuan Ding', 'Zongwen Chen', 'Zhiquan Xu', 'Xiaorong Liu', 'Daoqi Wu', 'Mingsi Gao', 'Mo Wang', 'Qiu Li']",,,,True
c3d69c9288a27fca5044723a7c9152d1f58b2795,medrxiv,Closed environments facilitate secondary transmission of coronavirus disease 2019 (COVID-19),doi.org/10.1101/2020.02.28.20029272,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Commissioned by the Minister of the Ministry of Health, Labour, and Welfare of Japan, we collected secondary transmission data with the aim of identifying high risk transmission settings. We show that closed environments contribute to secondary transmission of COVID-19 and promote superspreading events. Closed environments are consistent with large-scale COVID-19 transmission events such as that of the ski chalet-associated cluster in France and the church- and hospital-associated clusters in South Korea. Our findings are also consistent with the declining incidence of COVID-19 cases in China, as gathering in closed environments was prohibited in the wake of the rapid spread of the disease. Reduction of unnecessary close contact in closed environments may help prevent large case clusters and superspreading events.</jats:p>",2020-03-03,,,,,False
0b460e73926eb107001c95c0dfeae2362b4251b0,medrxiv,Precautions are Needed for COVID-19 Patients with Coinfection of Common Respiratory Pathogens,doi.org/10.1101/2020.02.29.20027698,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: With the ongoing outbreak of Coronavirus Disease 2019 (COVID-19), infected patients within and beyond the epidemic area, Wuhan, China, showed different epidemiological and clinical characteristics. There is a paucity of data concerning coinfection with other common respiratory pathogens in COVID-19 patients outside of Wuhan. Methods: We conducted a double-centre study recruiting 68 patients with severe acute respiratory coronavirus 2 (SARS-CoV-2) infection confirmed by nucleic acid testing in Qingdao and Wuhan from January 17 to February 16, 2020. Indirect immunofluorescence was performed to detect the specific IgM antibody against common respiratory pathogens in collected acute phase serum.  Results: Of the 68 patients with SARS-CoV-2 infection, 30 (44.12%) were from Qingdao. The median age of Qingdao and Wuhan patients were 50 (IQR: 37-59) and 31 (IQR: 28-38) years, respectively, and the majority of patients were female in Qingdao (60.00%) and Wuhan (55.26%). Among COVID-19 patients in Qingdao, 24 (80.00%) of them had IgM antibodies against at least one respiratory pathogen, whereas only one (2.63%) of the patients in Wuhan had positive results for serum IgM antibody detection (P&lt;0.0001). The most common respiratory pathogens detected in Qingdao COVID-19 patients were influenza virus A (60.00%) and influenza virus B (53.33%), followed by mycoplasma pneumoniae (23.33%) and legionella pneumophila (20.00%). While the pattern for coinfection in patients with community-acquired pneumonia in Qingdao was quite different, with a positive rate of only 20.90%.  Interpretation: We reported a large proportion of COVID-19 patients with coinfection of seasonal respiratory pathogens in Qingdao, northeast China, which differed greatly from the patients in Wuhan, central China. Precautions are needed when dealing with COVID-19 patients beyond the epidemic centre who have coinfection with other respiratory pathogens. We highly recommend adding SARS-CoV-2 to routine diagnostic testing in capable hospitals to prevent misdetection of the virus.</jats:p>",2020-03-03,"['Quansheng Xing', 'Guoju Li', 'Yuhan Xing', 'Ting Chen', 'Wenjie Li', 'Wei Ni', 'Kai Deng', 'Ruqin Gao', 'Changzheng Chen', 'Yang Gao', 'Qiang Li', 'Guiling Yu', 'Jianning Tong', 'Wei Li', 'Guiliang Hao', 'Yue Sun', 'Ai Zhang', 'Qin Wu', 'Zipu Li', 'Silin Pan']",,,,True
14783283da3482bf2aab4e6100fe4ea5c29d8db7,medrxiv,"Vicarious traumatization in the general public, members, and non-members of medical teams aiding in COVID-19 control",doi.org/10.1101/2020.02.29.20029322,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Since December 2019, more than 79,000 people have been diagnosed with infection of the Corona Virus Disease 2019 (COVID-19). A large number of medical staff were dispersed for Wuhan city and Hubei province to aid COVID-19 control. Psychological stress, especially vicarious traumatization (VT) caused by the COVID-19 pandemic, should not be ignored. To address this concern, the study employed a total of 214 general public (GP) and 526 nurses to evaluate VT scores via a mobile app-based questionnaire. Results showed that the VT scores slightly increased across periods of aiding COVID-19 control, although no statistical difference was noted (P = 0.083). However, the study found lower scores for VT in nurses [median = 69; interquartile range (IQR) = 56-85] than those of the GP (median = 75.5; IQR = 62-88.3) (P = 0.017). In addition, the VT scores for front-line nurses (FLNs; median = 64; IQR = 52-75), including scores for physiological and psychological responses, were significantly lower than those of non-front-line nurses (nFLNs; median = 75.5; IQR = 63-92) (P &lt; 0.001). Interestingly, the VT scores of the GP were significantly higher than those of the FLNs (P &lt; 0.001). However, no statistical difference was observed compared with those of nFLNs (P &gt; 0.05). Importantly, nFLNs are more likely to suffer from VT, which might be related to two factors, namely, gender [odds ratio (OR) = 3.1717; 95% confidence interval (CI) = 4.247-18.808; P = 0.002] and fertility [OR = 2.072; 95%CI = 0.626-24.533; P = 0.039]. Therefore, increased attention should be paid to the psychological problems of the medical staff, especially nFLNs, and GP under the situation of the spread and control of COVID-19. Early strategies that aim to prevent and treat VT in medical staff and GP are extremely necessary.</jats:p>",2020-03-03,"['Zhenyu Li', 'Jingwu Ge', 'Meiling Yang', 'Jianping Feng', 'Mei Qiao', 'Riyue Jiang', 'Jiangjiang Bi', 'Gaofeng Zhan', 'Xiaolin Xu', 'Long Wang', 'Qin Zhou', 'Chenliang Zhou', 'Yinbing Pan', 'Shijiang Liu', 'Haiwei Zhang', 'Jianjun Yang', 'Bin Zhu', 'Yimin Hu', 'Kenji Hashimoto', 'Yan Jia', 'Haofei Wang', 'Rong Wang', 'Cunming Liu', 'Chun Yang']",,,,True
0562f70516579d557cd1486000bb7aac5ccec2a1,medrxiv,Association of Cardiovascular Manifestations with In-hospital Outcomes in Patients with COVID-19: A Hospital Staff Data,doi.org/10.1101/2020.02.29.20029348,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: The outbreaks of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain a huge threat to the public health worldwide. Clinical data is limited up to now regarding the risk factors in favor of severe conversion of non-severe case with COVID-19. Aims: This study analyzed a hospital staff data to figure out general clinical features of COVID-19 in terms of the association of cardiovascular manifestations (CVMs) with in-hospital outcomes of COVID-19 cases.  Methods: Retrospective, single-center case series of 41 consecutive hospitalized health staff with confirmed COVID-19 were collected at the Central Hospital of Wuhan in Wuhan, China, from January 15 to January 24, 2020. Epidemiological, demographic, clinical, laboratory, radiological, treatment data and in-hospital adverse events were collected and analyzed. Final date of follow-up was March 3, 2020. A comparative study was applied between cases with CVMs and those without CVMs. Results: Of all, clinicians and clinical nurses accounted for 80.5%, while 87.8% of all had history of patient contact. The population was presented with a mean age of 39.1 +- 9.2 and less comorbidities than community population. The three most frequent symptoms of COVID-19 cases analyzed were fever (82.9%), myalgia or fatigue (80.5%) and cough (63.4%). While, the three most frequent initial symptoms were myalgia or fatigue (80.5%), fever (73.2%) and cough (41.5%). There were 95.1% cases featured as non-severe course of disease according to the official standard in China. Patients with CVMs and those without CVMs accounted for 58.5% and 41.5%, respectively. Compared with cases without CVMs, patients with CVMs were presented with lower baseline lymphocyte count (0.99 +- 0.43 and 1.55 +- 0.61, P&lt;0.001), more who had at least once positive nucleic acid detection of throat swab during admission (50.0% and 11.8%, P=0.011), and more received oxygen support (79.2% and 23.5%, P&lt;0.001). The rate of in-hospital adverse events was significantly higher in patients with CVMs group (75.0% and 23.5%, P=0.001). Multivariable logistic regression model indicated that, coexisting with CVMs in COVID-19 patients was not independently associated with in-hospital adverse events. Conclusions: Most of hospital staff with COVID-19 had history of patient contact, featured non-severe course of disease. Cases with CVMs suffered from more in-hospital adverse events than those without CVMs. But concomitant CVMs were not independently associated with in-hospital adverse events in COVID-19 patients.</jats:p>",2020-03-03,"['Ru Liu', 'Xiaoyan Ming', 'Ou Xu', 'Jianli Zhou', 'Hui Peng', 'Ning Xiang', 'Jiaming Zhang', 'Hong Zhu']",,,,True
f87eec8279bc79900914c5689bb42f49f41aace5,medrxiv,The spatiotemporal estimation of the dynamic risk and the international transmission of 2019 Novel Coronavirus (COVID-19) outbreak: A global perspective,doi.org/10.1101/2020.02.29.20029413,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>An ongoing novel coronavirus SARS-CoV-2 pneumonia infection outbreak called COVID-19 started in Wuhan, Hubei Province, China, in December 2019. It both spread rapidly to all provinces in China and started spreading around the world quickly through international human movement from January 2020. Currently, the spatiotemporal epidemic transmission patterns, prediction models, and possible risk analysis for the future are insufficient for COVID-19 but we urgently need relevant information, particularly from the global perspective. We have developed a novel two-stage simulation model to simulate the spatiotemporal changes in the number of COVID-19 cases and estimate the future worldwide risk. Based on the connectivity of countries to China and the country's medical and epidemic prevention capabilities, different scenarios are generated to analyze the possible transmission throughout the world and use this information to evaluate each country's vulnerability to and the dynamic risk of COVID-19. Countries' vulnerability to the COVID-19 outbreak from China is calculated for 63 countries around the world. Taiwan, South Korea, Hong Kong, and Japan are the most vulnerable areas. The relationship between each country's vulnerability and days before the first imported case occurred shows a very high exponential decrease. The cumulative number of cases in each country also has a linear relationship with vulnerability, which can compare and quantify the initial epidemic prevention capabilities to various countries' management strategies. In total, 1,000 simulation results of future cases around the world are generated for the spatiotemporal risk assessment. According to the simulation results of this study, if there is no specific medicine for it, it will likely form a global pandemic. This method can be used as a preliminary risk assessment of the spatiotemporal spread for a new global epidemic. * Note: This study was completed on February 15, 2020.</jats:p>",2020-03-03,"['Yuan-Chien Lin', 'Wan-Ju Chi', 'Yu-Ting Lin', 'Chun-Yeh Lai']",,,,True
c12ad8b411c24fe215be91d1f990645743e55ab5,medrxiv,An epidemiological forecast model and software assessing interventions on COVID-19 epidemic in China,doi.org/10.1101/2020.02.29.20029421,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>We develop a health informatics toolbox that enables public health workers to timely analyze and evaluate the time-course dynamics of the novel coronavirus (COVID-19) infection using the public available data from the China CDC. This toolbox is built upon a hierarchical epidemiological model in which two observed time series of daily proportions of infected and removed cases are emitted from the underlying infection dynamics governed by a Markov SIR infectious disease process. We extend the SIR model to incorporate various types of time-varying quarantine protocols, including government-level macro isolation policies and community-level micro inspection measures. We develop a calibration procedure for under-reported infected cases. This toolbox provides forecast, in both online and offline forms, of turning points of interest, including the time when daily infected proportion becomes smaller than the previous ones and the time when daily infected proportions becomes smaller than that of daily removed proportion, as well as the ending time of the epidemic. An R software is made available for the public, and examples on the use of this software are illustrated. Some possible extensions of our novel epidemiological models are discussed.</jats:p>",2020-03-03,"['Peter X Song', 'Lili Wang', 'Yiwang Zhou', 'Jie He', 'Bin Zhu', 'Fei Wang', 'Lu Tang', 'Marisa Eisenberg']",,,,True
d8fc77d8bfa634b9cc3462d0d6c6c938fa75c872,medrxiv,ddPCR: a more sensitive and accurate tool for SARS-CoV-2 detection in low viral load specimens,doi.org/10.1101/2020.02.29.20029439,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Real-Time PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load in patient throat and the limitation of RT-PCR, significant numbers of false negative reports are inevitable, which should not be ignored. Methods: We explored the feasibility of droplet digital PCR (ddPCR) to detect SARS-CoV-2 from 57 clinical pharyngeal swab samples and compared with RT-PCR in terms of the sensitivity and accuracy. Among 57 samples, all of which were reported as negative nucleic acid by officially approved clinical RT-PCR detection, 43 samples were collected from suspected patients with fever in clinic, and 14 were from supposed convalescents who were about to discharge after treatment. The experiment was double-blind. Results: The lower limit of detection of the optimized ddPCR is at least 500 times lower than that of RT-PCR. The overall accuracy of ddPCR for clinical detection is 94.3 %. 33 out of 35 negative pharyngeal swab samples checked by RT-PCR were correctly judged by ddPCR based on the follow-up investigation. In addition, 9 out of 14 (64.2 %) supposed convalescents with negative nucleic acid test twice by RT-PCR were positive by ddPCR detection. Conclusions: ddPCR shows superiority for clinical detection of SARS-CoV-2 to reduce the false negatives, which could be a powerful complement to the current standard RT-PCR. Before the ddPCR to be approved for diagnosis, the current clinical practice that the convalescent continues to be quarantined for 2 weeks is reasonable and necessary.</jats:p>",2020-03-06,"['Tao Suo', 'Xinjin Liu', 'Ming Guo', 'Jiangpeng Feng', 'Wenjia Hu', 'Yang Yang', 'Qiuhan Zhang', 'Xin Wang', 'Muhanmmad Sajid', 'Dong Guo', 'Zhixiang Huang', 'Liping Deng', 'Tielong Chen', 'Fang Liu', 'Ke Xu', 'Yuan Liu', 'Qi Zhang', 'Yingle Liu', 'Yong Xiong', 'Guozhong Guo', 'Yu Chen', 'Ke Lan']",,,,False
1ad1d4b84aea4ceaf05c62a1ad04e7150f7f4684,medrxiv,68 Consecutive patients assessed for COVID-19 infection; experience from a UK regional infectious disease unit,doi.org/10.1101/2020.02.29.20029462,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Clinical assessment of possible infection with SARS-CoV-2, the novel coronavirus responsible for the outbreak of COVID-19 respiratory illness, has been a major activity of infectious diseases services in the UK and elsewhere since the first report of cases in December 2019. We report our case series of 68 patients, reviewed by Infectious Diseases Consultants at a Regional Infectious Diseases Unit in the UK. We prospectively evaluated our service between the 29th Jan 2020 and 24th Feb 2020. Demographic, clinical, epidemiological and laboratory data were collected. We have compared clinical features and subsequent diagnosis between well patients not requiring admission for clinical reasons or antimicrobials with those assessed as needing either admission or antimicrobial treatment. Final microbiological diagnoses included SARS-CoV-2 (COVID-19), Mycoplasma pneumonia, influenza A, RSV, non SARS/MERS coronaviruses, rhinovirus/enterovirus. 9/68 were treated with antimicrobials, 15/68 were admitted to a negative pressure room of whom 5/68 were admitted solely due to an inability to isolate at home. Patients requiring either admission on clinical grounds or antimicrobials (14/68) were similar to those not requiring admission or antimicrobials, with modestly more fever and shortness of breath in the clinically admitted / antimicrobial group. The most commonly prescribed antimicrobials were doxycycline, moxifloxacin and oseltamivir. The majority of patients had mild illness which did not require a clinical intervention to manage. This finding supports a community testing approach supported by clinicians to review the proportion of more unwell patients.</jats:p>",2020-03-06,"['Nicholas Easom', 'Peter Moss', 'Gavin Barlow', 'Anda Samson', 'Tom Taynton', 'Kate Adams', 'Monica Ivan', 'Phillipa Burns', 'Kavitha Gajee', 'Kirstine Eastick', 'Patrick Lillie']",,,,True
7852aafdfb9e59e6af78a47af796325434f8922a,medrxiv,Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely associated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients,doi.org/10.1101/2020.02.29.20029520,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Although the SARS-CoV-2 viral load detection of respiratory specimen has been widely used for novel coronavirus disease (COVID-19) diagnosis, it is undeniable that serum SARS-CoV-2 nucleic acid (RNAaemia) could be detected  in  a fraction of the COVID-19 patients. However, it is not clear that if the incidence of RNAaemia could be correlated with the occurrence of cytokine storm or with the specific class of patients.  Methods: This study enrolled 48 patients with COVID-19 admitted to the General Hospital of Central Theater Command, PLA, a designated hospital in Wuhan, China. The patients were divided into three groups according to the Diagnosis and Treatment of New Coronavirus Pneumonia (version 6) published by the National Health Commission of China. The clinical and laboratory data were collected. The serum viral load detection and serum IL-6 levels were determined. Except for routine statistical analysis, Generalized Linear Models (GLMs) analysis was used to establish a patient status prediction model based on real-time RT-PCR Ct value. Findings: The Result showed that cases with RNAaemia were exclusively confirmed in critically ill patients group and appeared to reflect the illness severity. Further more, the inflammatory cytokine IL-6 levels were significantly elevated in critically ill patients, which is almost 10-folds higher than those in other patients. More importantly, the extremely high IL-6 level was closely correlated with the incidence of RNAaemia (R=0.902) and the vital signs of COVID-19 patients (R= -0.682).  Interpretation:    Serum SARS-CoV-2  viral load (RNAaemia) is strongly associated with cytokine storm and can be used to  predict the  poor prognosis of COVID-19 patients. Moreover, our results strongly suggest that cytokine IL-6 should be considered as a therapeutic target in critically ill patients with excessive inflammatory response.</jats:p>",2020-03-03,"['Xiaohua Chen', 'Binghong Zhao', 'Yueming Qu', 'Yurou Chen', 'Jie Xiong', 'Yong Feng', 'Dong Men', 'Qianchuan Huang', 'Ying Liu', 'Bo Yang', 'Jinya Ding', 'Feng Li']",,,,True
0bd443591b5e10934beef050b516afeca6b668fe,medrxiv,A simple model to assess Wuhan lock-down effect and region efforts during COVID-19 epidemic in China Mainland,doi.org/10.1101/2020.02.29.20029561,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Since COVID-19 emerged in early December, 2019 in Wuhan and swept across China Mainland, a series of large-scale public health interventions, especially Wuhan lock-down combined with nationwide traffic restrictions and Stay At Home Movement, have been taken by the government to control the epidemic. Based on Baidu Migration data and the confirmed cases data, we identified two key factors affecting the later (e.g February 27, 2020) cumulative confirmed cases in non-Wuhan region (y). One is the sum travelers from Wuhan during January 20 to January 26 (x1), which had higher infected probability but lower transmission ability because the human-to-human transmission risk of COVID-19 was confirmed and announced on January 20. The other is the seed cases from Wuhan before January 19, which had higher transmission ability and could be represented with the confirmed cases before January 29 (x2) due to a mean 10-day delay between infection and detection. A simple yet effective regression model then was established as follow: y= 70.0916+0.0054*x1+2.3455*x2 (n = 44, R2 = 0.9330, P&lt;10-7). Even the lock-down date only delay or in advance 3 days, the estimated confirmed cases by February 27 in non-Wuhan region will increase 35.21% or reduce 30.74% - 48.59%. Although the above interventions greatly reduced the human mobility, Wuhan lock-down combined with nationwide traffic restrictions and Stay At Home Movement do have a determining effect on the ongoing spread of COVID-19 across China Mainland. The strategy adopted by China has changed the fast-rising curve of newly diagnosed cases, the international community should learn from lessons of Wuhan and experience from China. Efforts of 29 Provinces and 44 prefecture-level cities against COVID-19 were also assessed preliminarily according to the interpretive model. Big data has played and will continue playing an important role in public health.</jats:p>",2020-03-03,"['Yuan zheming', 'Chen Yuan']",,,,True
b8bb4db131a25b1bbb30d4205b16dc9ef988d22f,medrxiv,Machine learning-based CT radiomics model for predicting hospital stay in patients with pneumonia associated with SARS-CoV-2 infection: A multicenter study,doi.org/10.1101/2020.02.29.20029603,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Abstract Objectives To develop and test machine learning-based CT radiomics models for predicting hospital stay in patients with pneumonia associated with SARS-CoV-2 infection. Design Cross-sectional Setting Multicenter Participants A total of 52 patients with laboratory-confirmed SARS-CoV-2 infection and their initial CT images were enrolled from 5 designated hospitals in Ankang, Lishui, Zhenjiang, Lanzhou, and Linxia between January 23, 2020 and February 8, 2020. As of February 20, patients remained in hospital or with non-findings in CT were excluded. Therefore, 31 patients with 72 lesion segments were included in the final analysis.  Intervention CT radiomics models based on logistic regression (LR) and random forest (RF) were developed on features extracted from pneumonia lesions in training and inter-validation datasets. The predictive performance was further evaluated in test dataset on lung lobe- and patients-level. Main outcomes Short-term hospital stay (≤10 days) and long-term hospital stay (&gt;10 days). Results The CT radiomics models based on 6 second-order features were effective in discriminating short- and long-term hospital stay in patients with pneumonia associated with SARS-CoV-2 infection, with areas under the curves of 0.97 (95%CI 0.83-1.0) and 0.92 (95%CI 0.67-1.0) by LR and RF, respectively, in the test dataset. The LR model showed a sensitivity and specificity of 1.0 and 0.89, and the RF model showed similar performance with sensitivity and specificity of 0.75 and 1.0 in test dataset.  Conclusions  The machine learning-based CT radiomics models showed feasibility and accuracy for predicting hospital stay in patients with pneumonia associated with SARS-CoV-2 infection.</jats:p>",2020-03-03,"['Xiaolong Qi', 'Zicheng Jiang', 'QIAN YU', 'Chuxiao Shao', 'Hongguang Zhang', 'Hongmei Yue', 'Baoyi Ma', 'Yuancheng Wang', 'Chuan Liu', 'Xiangpan Meng', 'Shan Huang', 'Jitao Wang', 'Dan Xu', 'Junqiang Lei', 'Guanghang Xie', 'Huihong Huang', 'Jie Yang', 'Jiansong Ji', 'Hongqiu Pan', 'Shengqiang Zou', 'Shenghong Ju']",,,,True
7e9cd4bbf0fba1cc0bcded40041fd01b9dfb683f,medrxiv,"Epidemiologic Characteristics of COVID-19 in Guizhou, China",doi.org/10.1101/2020.03.01.20028944,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>At the end of 2019, a coronavirus disease 2019 (COVID-19) outbroke in Wuhan, China, and spread to Guizhou province on January of 2020. To acquire the epidemiologic characteristics of COVID-19 in Guizhou, China, we collected data on 162 laboratory-confirmed cases related to COVID-19. We described the demographic characteristics of the cases and estimated the incubation period, serial interval and basic reproduction number. We also presented two representative case studies in Guizhou province -- Case Study 1 was an example of asymptomatic carrier; and Case Study 2 was an example of a large and complex infection chain that involved four different districts spanning three provinces and eight families. With an estimation of 8 days incubation period and 6 days serial interval, our results indicate that there may exist infectiousness during the incubation period for 2019-nCoV. This increases the difficulty of screening or identifying cases related to COVID-19.</jats:p>",2020-03-06,['Kaike Ping'],,,,True
f19e2df932f90f387fe71533f3802875d9042160,medrxiv,Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study,doi.org/10.1101/2020.03.01.20029074,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Coronavirus disease-2019 (COVID-19) is a rapidly escalating epidemic caused by SARS-CoV-2. Identification of a simple and effective indicator to assess disease severity and outcome is urgently needed.  Methods: This study retrospectively analyzed dynamic changes of lymphocyte percentage (LYM%) in 15 death cases, 15 severe cases as well as 40 moderate cases of COVID-19 patients. Next, prognostic role of lymphopenia in COVID-19 were verified in 92 hospitalized cases. Results: Our results from death and severe cases showed that LYM% in blood test were inversely associated with the progression and severity of COVID-19. LYM% in patients with moderate COVID-19 remained higher than 20% 10-12 days after symptom onset. In contrast, LYM% was lower than 20% in severe cases. However, LYM% in severe cases was higher than 5% 17-19 days after the onset of the disease, while it fell below 5% in death cases. Therefore, we established a reliable Time from symptom onset-LYM% model (TLM), which could be used to evaluate disease severity and predict the outcomes of hospitalized patients with COVID-19. Conclusion: Lymphopenia can be used to indicate clinical course, treatment effect and outcomes of COVID-19 patients.</jats:p>",2020-03-03,"['Li Tan', 'Qi Wang', 'Duanyang Zhang', 'Jinya Ding', 'Qianchuan Huang', 'Yi-Quan Tang', 'Qiongshu Wang', 'Hongming Miao']",,,,True
510ecab01c66bc2a911abcf67451ec482ed18a05,medrxiv,"Epidemiological and clinical features of 2019-nCoV acute respiratory disease cases in Chongqing municipality, China: a retrospective, descriptive, multiple-center study",doi.org/10.1101/2020.03.01.20029397,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background：In January 19, 2020, first case of 2019 novel coronavirus (2019-nCoV) pneumonia (COVID-19) was confirmed in Chongqing municipality, China. Methods：In this retrospective, descriptive, multiple-center study, total of 267 patients with COVID-19 confirmed by real-time RT-PCR in Chongqing from Jan 19 to Feb 16, 2020 were recruited. Epidemiological, demographic, clinical, radiological characteristics, laboratory examinations, and treatment regimens were collected on admission. Clinical outcomes were followed up until Feb 16, 2020.  Results：267 laboratory-confirmed COVID-19 patients admitted to 3 designated-hospitals in Chongqing provincial municipality from January 19 to February 16, 2020 were enrolled and categorized on admission. 217 (81.27%) and 50 (18.73%) patients were categorized into non-severe and severe subgroups, respectively. The median age of patients was 48.0 years (IQR, 35.0-65.0), with 129 (48.3%) of the patients were more than 50 years of age. 149 (55.8%) patients were men. Severe patients were significantly older (median age, 71.5 years [IQR, 65.8-77.0] vs 43.0 years [IQR, 32.5-57.0]) and more likely to be male (110 [50.7%] vs 39 [78.0%]) and have coexisting disorders (15 [30.0%] vs 26 [12.0%]). 41 (15.4%) patients had a recent travel to Hubei province, and 139 (52.1%) patients had a history of contact with patients from Hubei. On admission, the most common symptoms of COVID-19 were fever 225(84.3%), fatigue (208 [77.9%]), dry cough (189 [70.8%]), myalgia or arthralgia (136 [50.9%]). Severe patients were more likely to present dyspnea (17 [34.0%] vs 26 [12.0%]) and confusion (10 [20.0%] vs 15 [6.9%]). Rales (32 [12.0%]) and wheezes (20 [7.5%]) are not common noted for COVID-19 patients, especially for the non-severe (11 [5.1%], 10 [4.6%]). 118 (44.2%). Most severe patients demonstrated more laboratory abnormalities. 231 (86.5%), 61 (22.8%) patients had lymphopenia, leukopenia and thrombocytopenia, respectively. CD4+T cell counts decrease was observed in 77.1 % of cases, especially in the severe patients (45, 100%). 53.1% patients had decreased CD+3 T cell counts, count of CD8+T cells was lower than the normal range in part of patients (34.4%). More severe patients had lower level of CD4+ T cells and CD+3 T cells (45 [100.0%] vs 29[56.9%], 31 [68.9%] vs 20 [39.2%]). Most patients had normal level of IL-2, IL-4, TNF-α and INF-γ, while high level of IL-6 and IL-17A was common in COVID-19 patients (47 [70.1%], 35 [52.2%]). Level of IL-6, IL-17A and TNF-α was remarkably elevated in severe patients (32 [84.2%] vs 15 [51.7%], 25 [65.8%] vs 10 [34.5%], 17 [44.7%] vs 5 [17.2%]). All patients received antiviral therapy (267, 100%). A portion of severe patients (38, 76.0%) received systemic corticosteroid therapy. Invasive mechanical ventilation in prone position, non-invasive mechanical ventilation, high-flow nasal cannula oxygen therapy was adopted only in severe patients with respiratory failure (5[10.0%], 35[70.0%], 12[24.0%]). Traditional Chinese medicine was adopted to most of severe patients (43,86.0%). Conclusion:Our study firstly demonstrated the regional disparity of COVID-19 in Chongqing municipality and further thoroughly compared the differences between severe and non-severe patients. The 28-day mortality of COVID-19 patients from 3 designed hospitals of Chongqing is 1.5%, lower than that of Hubei province and mainland China including Hubei province. However, the 28-mortality of severe patients was relatively high, with much higher when complications occurred. Notably, the 28-mortality of critically severe patients complicated with severe ARDS is considerably as high as 44.4%. Therefore, early diagnosis and intensive care of critically severe COVID-19 cases, especially those combined with ARDS, will be considerably essential to reduce mortality.</jats:p>",2020-03-03,"['Di Qi', 'Xiaofeng Yan', 'Xumao Tang', 'Junnan Peng', 'Qian Yu', 'Longhua Feng', 'Guodan Yuan', 'An Zhang', 'Yaokai Chen', 'Jing Yuan', 'Xia Huang', 'Xianxiang Zhang', 'Peng Hu', 'Yuyan Song', 'Chunfang Qian', 'Qiangzhong Sun', 'Daoxin Wang', 'Jin Tong', 'Jianglin Xiang']",,,,True
6efe01046ce81279412ea440a4b246f942f29124,medrxiv,Systematic Review of the Registered Clinical Trials of Coronavirus Diseases 2019 (COVID-19),doi.org/10.1101/2020.03.01.20029611,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Since the outbreak of coronavirus diseases 2019 (COVID-19), many researchers in China have immediately carried out clinical research scheme of the COVID-19. But, there is still a lack of systematic review of registered clinical trials. Therefore, we made the first systematic review of the clinical trials of COVID-19 in order to provide evidence for the control of the COVID-19. Methods: The database from the Chinese Clinical Registration Center and the ClinicalTrials.gov were searched to collect the registered clinical trials of COVID-19. The retrieval inception date is February 9, 2020. Two evaluators independently selected literature, extracted data and evaluated the risk of bias. This study is based on the recommendations of PRISMA in Cochrane handbook. Results: A total of 75 COVID-19 registered clinical trials (63 interventional studies and 12 observational studies) were obtained. 97.3% of clinical trials were initiated by Chinese organizations. Only 11 trials have begun to recruit patients, and all registered clinical trials have not been completed. Most of the trials are early clinical exploratory trials or in pre-experiment stage (only two trials of Remdesivir in Ⅲ stage), and the sample size of subjects recruited is small. The main intervention methods include traditional Chinese medicine treatment, western medicine treatment and integrated Chinese and Western medicine treatment. The subjects were mainly non severe adult patients (≥ 18 years old). The main outcomes were clinical observation and examination. The duration of most trials was more than 5 months, and the median of the intervention study was 180 d (95% CI: 146.3 - 328.9 d); the median of the observation period was 334 d (95% CI: 166.6 - 363.4 d). Overall, both the methodology quality of intervention register trials and observational trials are low. Conclusions: Disorderly and intensive clinical trials of COVID-19 using traditional Chinese medicine and Western medicine are ongoing or will be carried out in China. However, based on the poor quality and small sample size and long completion period, we will not be able to obtain reliable, high-quality clinical evidence about COVID-19 treatment for quite a long time in the future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for the clinical trials of COVID-19 in China.</jats:p>",2020-03-03,"['Rui-fang Zhu', 'Ru-lu Gao', 'Sue-Ho Robert', 'Jin-ping Gao', 'Shi-gui Yang', 'Changtai Zhu']",,,,True
4bc43084ccdb8d3bb704ca577473169cd1a64f9c,medrxiv,Risk estimation and prediction by modeling the transmission of the novel coronavirus (COVID-19) in mainland China excluding Hubei province,doi.org/10.1101/2020.03.01.20029629,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: In December 2019, an outbreak of novel coronavirus disease (COVID-19) emerged in Wuhan, China and has swiftly spread to other parts of China and a number of oversea countries. Our aim is to evaluate the effectiveness of the evolution of interventions and self-protection measures, estimate the risk of partial lifting control measures and predict the epidemic trend of the virus in mainland China excluding Hubei province based on the published data and a novel mathematical model. Methods: A novel COVID-19 transmission dynamic model incorporating the intervention measures implemented in China is proposed. We parameterize the model by using the Markov Chain Monte Carlo (MCMC) method and estimate the control reproduction number Rc, as well as the effective daily reproduction ratio Re(t), of the disease transmission in mainland China excluding Hubei province. Results: The estimation outcomes indicate that the control reproduction number is 3.36 (95% CI 3.20-3.64) and Re(t) has dropped below 1 since January 31st, 2020, which implies that the containment strategies implemented by the Chinese government in mainland China excluding Hubei province are indeed effective and magnificently suppressed COVID-19 transmission. Moreover, our results show that relieving personal protection too early may lead to the spread of disease for a longer time and more people would be infected, and may even cause epidemic or outbreak again. By calculating the effective reproduction ratio, we proved that the contact rate should be kept at least less than 30% of the normal level by April, 2020. Conclusions: To ensure the epidemic ending rapidly, it is necessary to maintain the current integrated restrict interventions and self-protection measures, including travel restriction, quarantine of entry, contact tracing followed by quarantine and isolation and reduction of contact, like wearing masks, etc. People should be fully aware of the real-time epidemic situation and keep sufficient personal protection until April. If all the above conditions are met, the outbreak is expected to be ended by April in mainland China apart from Hubei province.</jats:p>",2020-03-06,"['Hui Wan', 'Jing-an Cui', 'Guo-Jing Yang']",,,,True
5f72fd41d7ba8d4d7de7aa1f83fc5c90ffa50b03,medrxiv,How does the outbreak of 2019-nCoV spread in mainland China? A retrospective analysis of the dynamic transmission routes,doi.org/10.1101/2020.03.01.20029645,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The fourth outbreak of the Coronaviruses, known as the 2019-nCoV, has occurred in Wuhan city of Hubei province in China in December 2019. We propose a time-varying sparse vector autoregressive (VAR) model to retrospectively analyze and visualize the dyamic transmission routes of this outbreak in mainland China over January 31 - February 19, 2020. Our results demonstrate that the influential inter-province routes from Hubei have become unidentifiable since February 4, whereas the self-transmission in each province was accelerating over February 4-15. From February 16, all routes became less detectable, and no influential transmissions could be identified on February 18 and 19. Such evidence supports the effectiveness of government interventions, including the travel restrictions in Hubei. Implications of our results suggest that in addition to the origin of the outbreak, virus preventions are of crucial importance in provinces with the largest migrant workers percentages (e.g., Jiangxi, Henan and Anhui) to controlling the spread of 2019-nCoV.</jats:p>",2020-03-06,"['Xiandeng Jiang', 'Le Chang', 'Yanlin Shi']",,,,True
1c46c38e29d7b6878d90e0aa66728d41dc4bf4da,medrxiv,The potential role of IL-6 in monitoring severe case of coronavirus disease 2019,doi.org/10.1101/2020.03.01.20029769,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Abstract.  Background:  The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan City, China spreads rapidly since December, 2019. Most patients show mild symptoms, but some of them develop into severe disease. There is currently no specific medication. The purpose of this study is to to explore changes of markers in peripheral blood of severe COVID-19 patients, which may be of value in disease monitoring. Methods Clinical data of patients with nonsevere and severe type COVID-19 diagnosed by laboratory test in our institution were collected. The relationship between peripheral blood cells and cytokines, clinical manifestation and outcome was analyzed. Results A total of 69 severe type COVID-19 patients were included. On admission, the median age of severe cases was 56-year old, with 52.17% female patient. The most common symptoms were fever (79.72%), cough (63.77%), shortness of breath (57.97%) and fatigue (50.72%). Diarrhea is less common. The most common comorbidity is hypertension. Upon admission, the proportion of bilateral pulmonary involvement and interstitial abnormalities evidenced by chest computed tomography (CT) imaging in severe cases was 60.87% and 27.54%, respectively. Compared with patients with nonsevere disease, those with severe disease showed obvious lymphocytopenia. Elevated level of lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin and D-dimer was found in most cases. Two patients (2.9%) needed transfer to the intensive care unit. Baseline immunological parameters and most of the inflammatory parameters were basically within the normal range. However, baseline interleukin-6 (IL-6) was significantly increased in severe type, which was closely related to the maximal body temperature during hospitalization and to CT findings. Baseline IL-6 was also significantly related to the increase of baseline level of CRP, LDH, ferritin and D-dimer. The increase of baseline IL-6 level suggests that it may positively correlate with the severity of COVID-19. Among the 30 severe type patients whose IL-6 was assessed before and after treatment, significant decrease in IL-6 and improved CT assessment was found in 25 patients after treatment. Whereas the IL-6 level was further increased in 3 cases, which was closely related to disease progression. It is suggested that IL-6 may be used as a marker for disease monitoring in severe COVID-19 patients. Conclusions On admission, the baseline level of IL-6, CRP, LDH and ferritin was closely related to the severity of COVID-19, and the elevated IL-6 was significantly related to the clinical manifestation of severe type patients. The decrease of IL-6 was closely related to treatment effectiveness, while the increase of IL-6 indicated disease exacerbation. Collectively, the dynamic change of IL-6 level can be used as a marker for disease monitoring in patients with severe COVID-19.</jats:p>",2020-03-06,"['Tao Liu', 'Jieying Zhang', 'Yuhui Yang', 'Hong Ma', 'Zhengyu Li', 'Jiaoyue Zhang', 'Ji Cheng', 'Xiaoyun Zhang', 'Yanxia Zhao', 'Zihan Xia', 'Liling Zhang', 'Gang Wu', 'Jianhua Yi']",,,,False
c8437a45bfb84fb206fe03fd18d28858bae32651,medrxiv,"Clinical and Laboratory Profiles of 75 Hospitalized Patients with Novel Coronavirus Disease 2019 in Hefei, China",doi.org/10.1101/2020.03.01.20029785,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The outbreak of the novel coronavirus disease 2019 (COVID-19) infection began in December 2019 in Wuhan, and rapidly spread to many provinces in China. The number of cases has increased markedly in Anhui, but information on the clinical characteristics of patients is limited. We reported 75 patients with COVID-19 in the First Affiliated Hospital of USTC from Jan 21 to Feb 16, 2020, Hefei, Anhui Province, China. COVID-19 infection was confirmed by real-time RT-PCR of respiratory nasopharyngeal swab samples. Epidemiological, clinical and laboratory data were collected and analyzed. Of the 75 patients with COVID-19, 61 (81.33%) had a direct or indirect exposure history to Wuhan. Common symptoms at onset included fever (66 [88.0%] of 75 patients) and dry cough (62 [82.67%]). Of the patients without fever, cough could be the only or primary symptom. The most prominent laboratory abnormalities were lymphopenia, decreased percentage of lymphocytes (LYM%), decreased CD4+ and CD8+ T cell counts, elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH). Patients with elevated interleukin 6 (IL-6) showed significant decreases in the LYM%, CD4+ and CD8+ T cell counts. Besides, the percentage of neutrophils, CRP, LDH and Procalcitonin levels increased significantly. We concluded that COVID-19 could cause different degrees of hematological abnormalities and damage of internal organs. Hematological profiles including LYM, LDH, CRP and IL-6 could be indicators of diseases severity and evaluation of treatment effectiveness. Antiviral treatment requires a comprehensive and supportive approach. Further targeted therapy should be determined based on individual clinical manifestations and laboratory indicators.</jats:p>",2020-03-06,"['Zonghao Zhao', 'Jiajia Xie', 'Ming Yin', 'Yun Yang', 'Hongliang He', 'Tengchuan Jin', 'Wenting Li', 'Xiaowu Zhu', 'Jing Xu', 'Changcheng Zhao', 'Lei Li', 'Yi Li', 'Hylemariam Mihiretie Mengist', 'Ayesha Zahid', 'Ziqin Yao', 'Chengchao Ding', 'Yingjie Qi', 'Yong Gao', 'Xiaoling Ma']",,,,True
2fe6b550f737baa47a5f2c8ab64cc3d9271c308a,medrxiv,Evaluation of the potential incidence of COVID-19 and effectiveness of contention measures in Spain: a data-driven approach,doi.org/10.1101/2020.03.01.20029801,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Our society is currently experiencing an unprecedented challenge, managing and containing an outbreak of a new coronavirus disease known as COVID-19. While China - were the outbreak started - seems to have been able to contain the growth of the epidemic, different outbreaks are nowadays being detected in multiple countries. Much is currently unknown about the natural history of the disease, such as a possible asymptomatic spreading or the role of age in both the susceptibility and mortality of the disease. Nonetheless, authorities have to take action and implement contention measures, even if not everything is known. To facilitate this task, we have studied the effect of different containment strategies that can be put into effect. Our work specifically refers to the situation in Spain as of February 28th, 2020, where a few dozens of cases have been detected. We implemented an SEIR-metapopulation model that allows tracing explicitly the spatial spread of the disease through data-driven stochastic simulations. Our results are in line with the most recent recommendations from the World Health Organization, namely, that the best strategy is the early detection and isolation of individuals with symptoms, followed by interventions and public recommendations aimed at reducing the transmissibility of the disease, which although not efficacious for disease eradication, would produce as a second-order effect a delay of several days in the raise of the number of infected cases</jats:p>",2020-03-06,"['Alberto Aleta', 'Yamir Moreno']",,,,True
d7111b44f2d13b24a11d55c8be2d2bbe6b245eac,medrxiv,COVID-19 Epidemic Outside China: 34 Founders and Exponential Growth,doi.org/10.1101/2020.03.01.20029819,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: In December 2019, pneumonia infected with a novel coronavirus burst in Wuhan, China. Now the situation is almost controlled in China but is worse outside China. We aimed to build a mathematical model to capture the global trend of epidemics outside China.  Methods: In this retrospective, outside-China diagnosis number reported from Jan 21 to Feb 28, 2020 was downloaded from WHO website. We develop a simple regression model on these numbers: log10 (Nt+34)=0.0515*t+2.075 where Nt is the total diagnosed patient till the ith day, t=1 at Feb 1.  Findings: Based on this model, we estimate that there have been about 34 unobserved founder patients at the beginning of spread outside China. The global trend is approximately exponential, with the rate of 10 folds every 19 days.</jats:p>",2020-03-03,"['Yi Li', 'Meng Liang', 'Xianhong Yin', 'Xiaoyu Liu', 'Meng Hao', 'Zixin Hu', 'Yi Wang', 'Li Jin']",,,,True
f8360b0e64d444215d21a61e056b070f12417e53,medrxiv,"Preliminary epidemiological analysis on children and adolescents with novel coronavirus disease 2019 outside Hubei Province, China: an observational study utilizing crowdsourced data",doi.org/10.1101/2020.03.01.20029884,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: The  outbreak of coronavirus disease 2019 (COVID-19) continues to expand across the world. Though both the number of cases and mortality rate in children and adolescents is reported to be low in comparison to adults, limited data has been reported on the outbreak with respect to pediatric patients. To elucidate information, we utilized crowdsourced data to perform a preliminary epidemiologic analysis of pediatric patients with COVID-19   Methods: In this observational study, data was collected from two open-access, line list crowdsourced online databases. Pediatric cases of COVID-19 were defined as patients ≤19 years of age with a laboratory confirmed diagnosis. The primary outcomes were case counts and cumulative case counts. Secondary outcomes included days between symptoms onset and first medical care and days between first medical care and reporting. Tertiary outcomes were rate of travel to Wuhan, rate of infected family members and rates of symptoms.   Results: A total of 82 patients were included. The median age was 10 [IQR: 5-15] years. Patients from mainland China (outside Hubei) accounted for 46.3% of cases, while the remaining 53.7% of cases were international. Males and females accounted for 52.4% and 32.9% of cases, respectively, with the remaining 14.6% being designated as unknown. A male skew persisted across subgroup analyses by age group (p=1.0) and location (inside/outside China) (p=0.22). While the number of reported international cases has been steadily increasing over the study period, the number of reported cases in China rapidly decreased from the start point. The median reporting delay was 3 [IQR: 2-4.8] days. The median delay between symptom onset and first seeking medical care was 1 [IQR: 0-3.25] day. In international cases, time to first seeking medical care was a median of 2.5 days longer than in China (p=0.04). When clinical features were reported, fever was the most common presentation (68.0%), followed by cough (36.0%).  Conclusions: The number of reported international pediatric COVID-19 cases is rapidly increasing. COVID-19 infections are, to-date, more common in males than females in both the children and adolescent age groups. Additionally, this male predominance remains the case both inside and outside of China. Crowdsourced data enabled early analysis of epidemiologic variables in pediatric patients with COVID-19. Further data sharing is required to enable analyses that are required to understand the course of this infection in children.</jats:p>",2020-03-06,"['Brandon Michael Henry', 'Maria Helena S Oliveira']",,,,True
d810f78f8850d9386abc6fdd8d652f2f85191753,medrxiv,The effect of human mobility and control measures on the COVID-19 epidemic in China,doi.org/10.1101/2020.03.02.20026708,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The ongoing COVID-19 outbreak has expanded rapidly throughout China. Major behavioral, clinical, and state interventions are underway currently to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, have affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was well explained by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases are still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China have substantially mitigated the spread of COVID-19.</jats:p>",2020-03-06,,,,,True
d85d142716f7f85cd27b54fc38a9e2968cf14346,medrxiv,Effects of weather-related social distancing on city-scale transmission of respiratory viruses,doi.org/10.1101/2020.03.02.20027599,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>BACKGROUND: Unusually high snowfall in western Washington State in February 2019 led to widespread school and workplace closures. We assessed the impact of social distancing caused by this extreme weather event on the transmission of respiratory viruses.  METHODS: Residual specimens from patients evaluated for acute respiratory illness at hospitals in the Seattle metropolitan area were screened for a panel of respiratory viruses. Transmission models were fit to each virus, with disruption of contact rates and care-seeking informed by data on local traffic volumes and hospital admissions.   RESULTS: Disruption in contact patterns reduced effective contact rates during the intervention period by 16% to 95%, and cumulative disease incidence through the remainder of the season by 3% to 9%. Incidence reductions were greatest for viruses that were peaking when the disruption occurred and least for viruses in early epidemic phase.  CONCLUSION: High-intensity, short-duration social distancing measures may substantially reduce total incidence in a respiratory virus epidemic if implemented near the epidemic peak.</jats:p>",2020-03-03,,,,,True
c697c2c3a6b1603212fd1f50d3b43a66f2f95775,medrxiv,"Monitoring Disease Transmissibility of 2019 Novel Coronavirus Disease in Zhejiang, China",doi.org/10.1101/2020.03.02.20028704,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>We monitored the transmissibility of 2019 novel coronavirus disease in Zhejiang accounting the transmissions from imported cases. Even though Zhejiang is one of the worst-affected provinces, an interruption of disease transmission (i.e. instantaneous reproduction numbers &lt;1) was observed in early/mid-February after an early social-distancing response to the outbreak.</jats:p>",2020-03-05,"['Ka Chun Chong', 'Wei Cheng', 'Shi Zhao', 'Feng Ling', 'Kirran N Mohammad', 'Maggie Haitian Wang', 'Benny Chung-ying Zee', 'Lesley Wei', 'Xi Xiong', 'Hengyan Liu', 'Jingxuan Wang', 'Enfu Chen']",,,,False
70cc2e5152d3dc4d44494124ff556c9bbe9e6f41,medrxiv,"Clinical Characteristics of Patients with Severe Pneumonia Caused by the 2019 Novel Coronavirus in Wuhan, China",doi.org/10.1101/2020.03.02.20029306,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Abstract Background: A new virus broke out in Wuhan, Hubei, China, and was later named 2019 novel coronavirus (2019-nCoV). The clinical characteristics of severe pneumonia caused by 2019-nCoV are still not clear. Objectives: The aim of this study was to explore the clinical characteristics and risk factors of the severe pneumonia caused by the 2019-nCoV in Wuhan, China. Method: The study included patients hospitalized at the central hospital of Wuhan who had been diagnosed with a pneumonia caused by the novel coronavirus. Clinical features, chronic co-morbidities, demographic data, laboratory examinations, and chest computed tomography (CT) scans were reviewed through electronic medical records. SPSS was used for data analysis to explore the clinical characteristics and risk factors of the patients with the severe pneumonia. Results: A total of 110 patients diagnosed with 2019 novel coronavirus pneumonia were included in the study, including 38 with severe pneumonia and 72 with non-severe pneumonia. Statistical analysis showed that advanced age, an increase of D-dimer, and a decrease of lymphocytes were characteristics of the patients with severe pneumonia. Moreover, in the early stage of the disease, chest CT scans of patients with the severe pneumonia showed the illness can progress rapidly. Conclusions: Advanced age, lymphocyte decline, and D-dimer elevation are important characteristics of patients with severe pneumonia. Clinicians should focus on these characteristics to identify high-risk patients at an early stage.</jats:p>",2020-03-03,"['Yafei Wang', 'Ying Zhou', 'Zhen Yang', 'Dongping Xia', 'Shuang Geng']",,,,True
f82372b109168b411344f537210c63cc6ed323ed,medrxiv,"The Seattle Flu Study: a multi-arm community-based prospective study protocol for assessing influenza prevalence, transmission, and genomic epidemiology",doi.org/10.1101/2020.03.02.20029595,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Introduction. Influenza epidemics and pandemics cause significant morbidity and mortality. An effective response to a potential pandemic requires the infrastructure to rapidly detect, characterize, and potentially contain new and emerging influenza strains at a population level. The objective of this study is to use data gathered simultaneously from community and hospital sites to develop a model of how influenza enters and spreads in a population.  Methods and Analysis. Starting in the 2018-19 season, we have been enrolling individuals with acute respiratory illness from community sites throughout the Seattle metropolitan area, including clinics, childcare facilities, Seattle-Tacoma International Airport, workplaces, college campuses, and homeless shelters. At these sites, we collect clinical data and mid-nasal swabs from individuals with at least two acute respiratory symptoms. Additionally, we collect residual nasal swabs and data from individuals who seek care for respiratory symptoms at four regional hospitals. Samples are tested using a multiplex molecular assay, and influenza whole genome sequencing is performed for samples with influenza detected. Geospatial mapping and computational modeling platforms are in development to characterize the regional spread of influenza and other respiratory pathogens.  Ethics and Dissemination. The study was approved by the University of Washington's Institutional Review Board. Results will be disseminated through talks at conferences, peer-reviewed publications, and on the study website (www.seattleflu.org).</jats:p>",2020-03-06,"['Helen Y. Chu', 'Michael Boeckh', 'Janet A. Englund', 'Michael Famulare', 'Barry R. Lutz', 'Deborah A Nickerson', 'Mark J. Rieder', 'Lea M Starita', 'Amanda Adler', 'Elisabeth Brandstetter', 'Chris D. Frazar', 'Peter D. Han', 'Reena K. Gularti', 'James Hadfield', 'Michael L. Jackson', 'Anahita Kiavand', 'Louise E. Kimball', 'Kirsten Lacombe', 'Jennifer Logue', 'Victoria Lyon', 'Kira L. Newman', 'Thomas R. Sibley', 'Monica L. Zigman Suschsland', 'Caitlin Wolf', 'Jay Shendure', 'Trevor Bedford']",,,,True
5796fdc80a85b6e634a279c57711356055b65880,medrxiv,Close contacts and household transmission of SARS-CoV-2 in China: a content analysis based on local Heath Commissions' public disclosures.,doi.org/10.1101/2020.03.02.20029868,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Public disclosure from Chinese local Health Commissions show that male and mid-aged index patients are the major source of virus from outside to the households. This implies that two important actions should be taken in disease control. First considers the kindergarten and school closure time. Local kindergarten and primary schools should postpone their admission and regular operation, to at least not earlier than local secondary schools. Second, workplace hygiene is of particular important in the next phase of disease control. As travel restrictions within China are being gradually lifted, we suggest that workplace hygiene should be taken serious care in the next month or two.</jats:p>",2020-03-06,"['xiaoke Xu', 'Xiaofan Liu', 'Ye Wu', 'Sheikh Taslim ALI']",,,,True
ebed882da10cbf669cbb86802e9fa07a4a33ef91,medrxiv,"Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome",doi.org/10.1101/2020.03.02.20029975,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, December 2019, and continuously poses a serious threat to public health. Our previous study has shown that cytokine storm occurred during SARS-CoV-2 infection, while the detailed role of cytokines in the disease severity and progression remained unclear due to the limited case number. In this study, we examined 48 cytokines in the plasma samples from 53 COVID-19 cases, among whom 34 were severe cases, and the others moderate. Results showed that 14 cytokines were significantly elevated upon admission in COVID-19 cases. Moreover, IP-10, MCP-3, and IL-1ra were significantly higher in severe cases, and highly associated with the PaO2/FaO2 and Murray score. Furthermore, the three cytokines were independent predictors for the progression of COVID-19, and the combination of IP-10, MCP-3 and IL-1ra showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations. Serial detection of IP-10, MCP-3 and IL-1ra in 14 severe cases showed that the continuous high levels of these cytokines were associated with disease deterioration and fatal outcome. In conclusion, we report three cytokines that closely associated with disease severity and outcome of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, which suggested novel therapeutic targets and strategy.</jats:p>",2020-03-06,"['Yang Yang', 'Chenguang Shen', 'Jinxiu Li', 'Jing Yuan', 'Minghui Yang', 'Fuxiang Wang', 'Guobao Li', 'Yanjie Li', 'Li Xing', 'Ling Peng', 'Jinli Wei', 'Mengli Cao', 'Haixia Zheng', 'Weibo Wu', 'Rongrong Zou', 'Delin Li', 'Zhixiang Xu', 'Haiyan Wang', 'Mingxia Zhang', 'Zheng Zhang', 'Lei Liu', 'Yingxia Liu']",,,,True
c8df44a3612e85e267351e936ddeb8fc5867afa1,medrxiv,The timing of one-shot interventions for epidemic control,doi.org/10.1101/2020.03.02.20030007,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The apparent early success in China's large-scale intervention to control the COVID-19 epidemic has led to interest in whether other countries can replicate it as well as concerns about a resurgence of the epidemic if or when China relaxes the interventions.  In this paper we look at the impact of a single short-term intervention on an epidemic.  We see that if an intervention cannot be sustained long-term, it has the greatest impact if it is imposed once infection levels have become large enough that there is an appreciable number of infections present.  For minimising the total number infected it should start close to the peak so that there is no rebound once the intervention is stopped, while to minimise the peak prevalence, it should start earlier, allowing two peaks of comparable size rather than one very large peak.  In populations with distinct subgroups, synchronized interventions are less effective than targeting the interventions in each sub-population separately.      We do not attempt to clearly determine what makes an intervention sustainable or not.  We believe that is a policy question.  If an intervention is sustainable, it should be kept in place.  Our intent is to offer insight into how best to time an intervention whose impact on society is too great to maintain.</jats:p>",2020-03-06,"['Francesco Di Lauro', 'István Z Kiss', 'Joel Miller']",,,,True
d0b33d173f1d32662e2ad8d7e85181f9b23f010c,medrxiv,Estimation of COVID-19 outbreak size in Italy based on international case exportations,doi.org/10.1101/2020.03.02.20030049,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Italy is currently experiencing an epidemic of COVID-19 which emerged in the Lombardy region . During the interval between February 25-29, 2020, we identified 46 cases of COVID-19 reported in 21 countries in Europe, Africa, North America, and South America which were either in individuals with recent travel from Italy, or who had presumed infection by a traveler from Italy 2. In six cases, in four of the affected countries (Switzerland, France, Austria, Croatia), land travel was a likely route of introduction, or was documented to have been the route of introduction. 	We used air travel volume between Italian cities and cities in other countries as an index of connectedness, using data available from the International Air Transport Association (IATA) for February 2015 (2.61 million total departing international air passengers from Italy). We used the methods of Fraser et al. to estimate the size of the underlying epidemic in Italy necessary in order for these cases to be observed with a reasonable probability. To estimate the time at risk of COVID-19 exposure for travelers departing Italy, we obtained data from the United Nations World Tourism Organization (UNWTO) for the proportion of international travelers that are non-residents of Italy (63%) and the average length of stay of tourists to Italy (3.4 days), and assumed the Italian epidemic began one month prior to February 29, 2020.  We also performed sensitivity analyses in which we included outbound travel to all countries regardless of reported case importations, inflated travel volumes by 35%, to account for the relative increase in flight numbers from 2015-2019, and excluded cases in bordering countries and which were documented to have been introduced by overland travel. 	When all cases were considered we estimated a true outbreak size of 3971 cases (95% CI 2907-5297), as compared to a reported case count of 1128 on February 29, 2020, suggesting non-identification of 72% (61-79%) of cases. In sensitivity analyses, outbreak sizes varied from 1552 to 4533 cases (implying non-identification of 27-75% of cases). 	We recently used similar methods to estimate a much larger epidemic size in Iran, with a far greater degree of under-reporting, based on many fewer exported cases. The reason for this difference relates to the relatively high volume of travel from Italy, relative to Iran. In summary, we suggest that the numerous COVID-19 case exportations from Italy in recent days suggest an epidemic that is larger than official case counts suggest, and which is approximately on a par with that currently occurring in South Korea, which reports 3526 cases (and fewer deaths) as of February 29, 2020.</jats:p>",2020-03-06,"['Ashleigh Tuite', 'Victoria Ng', 'Erin Rees', 'David Fisman']",,,,True
eca60315d09691e694c6f372ff83a349b4864a88,medrxiv,Forecasting the Cumulative Number of COVID-19 Deaths in China: Can More Lives Be Saved?,doi.org/10.1101/2020.03.02.20030064,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: An outbreak of 2019 novel coronavirus diseases (COVID-19) caused by SARS-CoV-2 is on-going in China and appears to approach late phase. It is highly demanding to estimate how many COVID-19 patients will die eventually. In this study, an estimate of the potential total number of COVID-19 deaths in mainland China, Hubei Province, Wuhan City, and other provinces is provided. The results may help to eluate the severity of the epidemic and facilitate mental health care.   Methods: Data of the cumulative number of COVID-19 deaths from January 21 to February 29, 2020, released daily by the National Health Commission of China and Hubei Provincial Health Commission, were used. The Boltzmann function was explored to simulate the data in each region. By using these established functions, the potential total number of deaths were forecasted. In addition, data of the cumulative number of 2003 SARS deaths in mainland China, Hong Kong and worldwide were collected from the WHO official website and analyzed in a similar manner. A Monte Carlo technique was applied to analyze the uncertainty of the estimates of the cumulative confirmed cases, and the results are presented using the resulting mean, median, and a 95% confidence interval (CI). For comparison, the potential total numbers of deaths were estimated by Richards function-based regression analyses.  Findings: The data of cumulative number of COVID-19 deaths with respect to each region were all well-fitted to the Boltzmann function (R2 for all the regression analyses being close to 0.999). Consistently, the data for the cumulative numbers of 2003 SARS in mainland China, Hong Kong and worldwide were also well fitted to the Boltzmann function. The potential total number of COVID-19 deaths in mainland China, other provinces, Hubei Province, Wuhan City, and other cities in Hubei were estimated to be 3260 (95% CI 3187, 3394), 110 (109, 112), 3174 (3095, 3270), 2550 (2494, 2621) and 617 (607, 632), respectively. Similar results were obtained by Richards function-based regression analysis.  Interpretation: The observation that the data of the cumulative numbers of deaths for both the on-going COVID-19 outbreak and the 2003 SARS epidemic in each geographic region were well fitted with the Boltzmann function strongly suggests that it is suitable for the simulation of deaths associated with coronaviruses-induced diseases. The estimation of COVID-19 deaths may help governments to evaluate the severity of the outbreak and also facilitate timely mental health care for the families of dead patients.</jats:p>",2020-03-03,"['Zuqin Zhang', 'Cheng Long', 'Wei Yao', 'Qi Ying', 'Xinmiao Fu']",,,,False
3b181a741d4beafda3ba3a8fc68239493d49f6aa,medrxiv,"Estimation of local novel coronavirus (COVID-19) cases in Wuhan, China from off-site reported cases and population flow data from different sources",doi.org/10.1101/2020.03.02.20030080,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Backgrounds: In December 2019, a novel coronavirus (COVID-19) pneumonia hit Wuhan, Hubei Province, China and spread to the rest of China and overseas. The emergence of this virus coincided with the Spring Festival Travel Rush in China. It is possible to estimate total number of cases of COVID-19 in Wuhan, by 23 January 2020, given the cases reported in other cities and population flow data between cities. Methods: We built a model to estimate the total number of cases in Wuhan by 23 January 2020, based on the number of cases detected outside Wuhan city in China, with the assumption that if the same screening effort used in other cities applied in Wuhan. We employed population flow data from different sources between Wuhan and other cities/regions by 23 January 2020. The number of total cases was determined by the maximum log likelihood estimation.  Findings: From overall cities/regions data, we predicted 1326 (95% CI: 1177, 1484), 1151 (95% CI: 1018, 1292) and 5277 (95% CI: 4732, 5859) as total cases in Wuhan by 23 January 2020, based on different source of data from Changjiang Daily newspaper, Tencent, and Baidu. From separate cities/regions data, we estimated 1059 (95% CI: 918, 1209), 5214 (95% CI: 4659, 5808) as total cases in Wuhan in Wuhan by 23 January 2020, based on different sources of population flow data from Tencent and Baidu. Conclusion: Sources of population follow data and methods impact the estimates of local cases in Wuhan before city lock down.  Keyword: COVID-19; mobility; pneumonia; transportation; outbreaks</jats:p>",2020-03-02,"['Zian Zhuang', 'Peihua Cao', 'Shi Zhao', 'Yijun Lou', 'Weiming Wang', 'Shu Yang', 'Lin Yang', 'Daihai He']",,,,True
267729947ca478946d5a4bffb8e13d50c3545120,medrxiv,Rapid Detection of SARS-CoV-2 Using Reverse transcription RT-LAMP method,doi.org/10.1101/2020.03.02.20030130,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Corona Virus Disease 2019 (COVID-19) is a recently emerged life-threatening disease caused by SARS-CoV-2. Real- time fluorescent PCR (RT-PCR) is the clinical standard for SARS-CoV-2 nucleic acid detection. To detect SARS-CoV-2 early and control the disease spreading on time, a faster and more convenient method for SARS-CoV-2 nucleic acid detecting, RT-LAMP method (reverse transcription loop-mediated isothermal amplification) was developed. RNA reverse transcription and nucleic acid amplification were performed in one step at 63 ℃ isothermal conditions, and the results can be obtained within 30 minutes. ORF1ab gene, E gene and N gene were detected at the same time. ORF1ab gene was very specific and N gene was very sensitivity, so they can guarantee both sensitivity and specificity for SARS-CoV-2. The sensitivity of RT-LAMP assay is similar to RT-PCR, and specificity was 99% as detecting 208 clinical specimens. The RT-LAMP assay reported here has the advantages of rapid amplification, simple operation, and easy detection, which is useful for the rapid and reliable clinical diagnosis of SARS-CoV-2.</jats:p>",2020-03-02,"['Weihua Yang', 'Xiaofei Dang', 'Qingxi Wang', 'Mingjie Xu', 'Qianqian Zhao', 'Yunying Zhou', 'Huailong Zhao', 'Li Wang', 'Yihui Xu', 'Jun Wang', 'Shuyi Han', 'Min Wang', 'Fengyan Pei', 'Yunshan Wang']",,,,True
b53dd68cad40cbcd698a848f53853e5f03d44a1f,medrxiv,Validity of Wrist and Forehead Temperature in Temperature Screening in the General Population During the Outbreak of 2019 Novel Coronavirus: a prospective real-world study,doi.org/10.1101/2020.03.02.20030148,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Aims: Temperature screening is important in the population during the outbreak of 2019 Novel Coronavirus (COVID-19). This study aimed to compare the accuracy and precision of wrist and forehead temperature with tympanic temperature under different circumstances. Methods: We performed a prospective observational study in a real-life population. We consecutively collected wrist and forehead temperatures in Celsius (C) using a non-contact infrared thermometer (NCIT). We also measured the tympanic temperature using a tympanic thermometers (IRTT) and defined fever as a tympanic temperature ≥37.3C. Results: We enrolled a total of 528 participants including 261 indoor and 267 outdoor participants. We divided outdoor participants into four types according to their means of transportation to the hospital as walk, bicycle, electric vehicle, car, and inside the car. Under different circumstance, the mean difference ranged from -1.72 to -0.56C in different groups for the forehead measurements, and -0.96 to -0.61C for the wrist measurements. Both measurements had high fever screening abilities in inpatients (wrist: AUC 0.790; 95% CI: 0.725-0.854, P &lt;0.001; forehead: AUC 0.816; 95% CI: 0.757-0.876, P &lt;0.001). The cut-off value of wrist measurement for detecting tympanic temperature ≥37.3C was 36.2C with a 86.4% sensitivity and a 67.0% specificity, and the best threshold of forehead measurement was also 36.2C with a 93.2% sensitivity and a 60.0% specificity. Conclusions: Wrist measurement is more stable than forehead measurement under different circumstance. Both measurements have great fever screening abilities for indoor patients. The cut-off value of both measurements was 36.2C.</jats:p>",2020-03-06,"['Ge Chen', 'Jiarong Xie', 'Guangli Dai', 'Peijun Zheng', 'Xiaqing Hu', 'Hongpeng Lu', 'Lei Xu', 'Xueqin Chen', 'Xiaomin Chen']",,,,True
ff067164497bcfbd9145be223dcd2b05f159dd63,medrxiv,Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019,doi.org/10.1101/2020.03.02.20030189,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Summary Background The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patient remains largely unknown, and the clinical values of antibody testing have not been fully demonstrated. Methods A total of 173 patients with confirmed SARS-CoV-2 infection were enrolled. Their serial plasma samples (n = 535) collected during the hospitalization period were tested for total antibodies (Ab), IgM and IgG against SARS-CoV-2 using immunoassays. The dynamics of antibodies with the progress and severity of disease was analyzed. Findings Among 173 patients, the seroconversion rate for Ab, IgM and IgG was 93.1% (161/173), 82.7% (143/173) and 64.7% (112/173), respectively. Twelve patients who had not seroconverted were those only blood samples at the early stage of illness were collected. The seroconversion sequentially appeared for Ab, IgM and then IgG, with a median time of 11, 12 and 14 days, respectively. The presence of antibodies was &lt; 40% among patients in the first 7 days of illness, and then rapidly increased to 100.0%, 94.3% and 79.8% for Ab, IgM and IgG respectively since day 15 after onset. In contrast, the positive rate of RNA decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15 to 39. Combining RNA and antibody detections significantly improved the sensitivity of pathogenic diagnosis for COVID-19 patients (p &lt; 0.001), even in early phase of 1-week since onset (p = 0.007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (p = 0.006). Interpretation The antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.</jats:p>",2020-03-03,"['Juanjuan Zhao', 'Quan Yuan', 'Haiyan Wang', 'Wei Liu', 'Xuejiao Liao', 'Yingying Su', 'Xin Wang', 'Jing Yuan', 'Tingdong Li', 'Jinxiu Li', 'Shen Qian', 'Congming Hong', 'Fuxiang Wang', 'Yingxia Liu', 'Zhaoqin Wang', 'Qing He', 'Zhiyong Li', 'Bin He', 'Tianying Zhang', 'Shengxiang Ge', 'Lei Liu', 'Jun Zhang', 'Ningshao Xia', 'Zheng Zhang']",,,,True
fdcf4d5226d681e9038aae6cc922e0cf5d6514b7,medrxiv,Estimating the burden of United States workers exposed to infection or disease: a key factor in containing risk of COVID-19 infection,doi.org/10.1101/2020.03.02.20030288,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Introduction: With the global spread of COVID-19, there is a compelling public health interest in quantifying who is at increased risk of disease. Occupational characteristics, such as interfacing with the public and being in close quarters with other workers, not only put workers at high risk for disease, but also make them a nexus of disease transmission to the community. This can further be exacerbated through presenteeism, the term used to describe the act of coming to work despite being symptomatic for disease. Understanding which occupational groups are exposed to infection and disease in the workplace can help to inform public health risk response and management for COVID-19, and subsequent infectious disease outbreaks.  Methods: To estimate the burden of United States workers exposed to infection and disease in the workplace, national employment data (by Standard Occupational Classification) maintained by the Bureau of Labor Statistics (BLS) was merged with BLS O*NET survey data, which ranks occupations with particular physical, ergonomic, and structural exposures. For this analysis, occupations reporting exposure to infection or disease more than once a month was the focus.    Results: Based on our analyses, approximately 10% (14.4 M) of United States workers are employed in occupations where exposure to disease or infection occurs at least once per week. Approximately 18.4% (26.7 M) of all United States workers are employed in occupations where exposure to disease or infection occurs at least once per month. While the majority of exposed workers are employed in healthcare sectors, other occupational sectors also have high proportions of exposed workers. These include protective service occupations (e.g. police officers, correctional officers, firefighters), office and administrative support occupations (e.g. couriers and messengers, patient service representatives), education occupations (e.g. preschool and daycare teachers), community and social services occupations (community health workers, social workers, counselors), and even construction and extraction occupations (e.g. plumbers, septic tank installers, elevator repair).   Conclusions: The large number of persons employed in a wide variety of occupations with frequent exposure to infection and disease underscore the importance of all workplaces developing risk response plans for COVID-19. This work also serves as an important reminder that the workplace is a key locus for public health interventions, which could protect both workers and the communities they serve.</jats:p>",2020-03-06,"['Marissa G Baker', 'Trevor K Peckham', 'Noah S. Seixas']",,,,False
7fb7c0c48b30e66dfaea5fdec16d999ed52d1ee0,medrxiv,Preliminary estimating the reproduction number of the coronavirus disease (COVID-19) outbreak in Republic of Korea and Italy by 5 March 2020,doi.org/10.1101/2020.03.02.20030312,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The novel coronavirus disease 2019 (COVID-19) outbreak and Italy has caused 6088 cases and 41 deaths in Republic of Korea and 3144 cases and 107 death in Italy by 5 March 2020. We modeled the transmission process in Republic of Korea and Italy with a stochastic model and estimated the basic reproduction number R0 as 2.6 (95% CI: 2.3-2.9) or 3.2 (95% CI: 2.9-3.5) in Republic of Korea, under the assumption that the exponential growth starting on 31 January or 5 February 2020, and 2.6 (95% CI: 2.3-2.9) or 3.3 (95% CI: 3.0-3.6) in Italy, under the assumption that the exponential growth starting on 5 February or 10 February 2020. Estimates of dispersion term (k) were 10 (95% CI: 5-56) or 22 (95% CI: 8-61) in Republic of Korea, and 13 (95% CI: 5-61) or 37 (95% CI: 13-61) in Italy, and all of which imply few super-spreading events.</jats:p>",2020-03-06,"['Zian Zhuang', 'Shi Zhao', 'Qianying Lin', 'Peihua Cao', 'Yijun Lou', 'Lin Yang', 'Shu Yang', 'Daihai He', 'Li Xiao']",,,,True
e5163021a1b88e2c2335cca27fbfcf883f870830,medrxiv,Preliminary estimation of the novel coronavirus disease (COVID-19) cases in Iran: a modelling analysis based on overseas cases and air travel data,doi.org/10.1101/2020.03.02.20030320,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>As of 1 March 2020, Iran has reported 987 COVID-19 cases and including 54 associated deaths. At least six neighboring countries (Bahrain, Iraq, Kuwait, Oman, Afghanistan and Pakistan) have reported imported COVID-19 cases from Iran. We used air travel data and the cases from Iran to other Middle East countries and estimated 16533 (95% CI: 5925, 35538) COVID-19 cases in Iran by 25 February, before UAE and other Gulf Cooperation Council countries suspended inbound and outbound flights from Iran.</jats:p>",2020-03-06,"['Zian Zhuang', 'Shi Zhao', 'Qianying Lin', 'Peihua Cao', 'Yijun Lou', 'Lin Yang', 'Daihai He']",,,,True
49ac69f362c27acbc6de0c5cbb640267e7a1e797,medrxiv,"Clinical features and outcomes of 221 patients with COVID-19 in Wuhan, China",doi.org/10.1101/2020.03.02.20030452,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Rationale: In late December 2019, an outbreak of acute respiratory illness, now officially named as COVID-19, or coronavirus disease 2019, emerged in Wuhan, China, now spreading across the whole country and world. More data were needed to understand the clinical characteristics of the disease.  Objectives: To study the epidemiology, clinical features and outcomes of patients with COVID-19.  Methods: we performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital.   Measurements and Main Results: The median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%.  Conclusions: The COVID-19 epidemic spreads rapidly by human-to-human transmission. Patients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes.   Keywords: coronavirus disease 2019; clinical features; outcomes; severe patients</jats:p>",2020-03-06,"['Guqin Zhang', 'Chang Hu', 'Linjie Luo', 'Fang Fang', 'Yongfeng Chen', 'Jianguo Li', 'Zhiyong Peng', 'Huaqin Pan']",,,,True
3a73b880acd8983f87b210ff7fee434fd6ecc8c8,medrxiv,"Epidemiology and Transmission of COVID-19 in Shenzhen China: Analysis of 391 cases and 1,286 of their close contacts",doi.org/10.1101/2020.03.03.20028423,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Abstract  Background Rapid spread of SARS-CoV-2 in Wuhan prompted heightened surveillance in Shenzhen and elsewhere in China. The resulting data provide a rare opportunity to measure key metrics of disease course, transmission, and the impact of control.  Methods The Shenzhen CDC identified 391 SARS-CoV-2 cases from January 14 to February 12, 2020 and 1286 close contacts. We compare cases identified through symptomatic surveillance and contact tracing, and estimate the time from symptom onset to confirmation, isolation, and hospitalization. We estimate metrics of disease transmission and analyze factors influencing transmission risk.   Findings Cases were older than the general population (mean age 45) and balanced between males (187) and females (204). Ninety-one percent had mild or moderate clinical severity at initial assessment. Three have died, 225 have recovered (median time to recovery is 32 days). Cases were isolated on average 4.6 days after developing symptoms; contact tracing reduced this by 1.9 days. Household contacts and those travelling with a case where at higher risk of infection (ORs 6 and 7) than other close contacts. The household secondary attack rate was 15%, and children were as likely to be infected as adults. The observed reproductive number was 0.4, with a mean serial interval of 6.3 days.   Interpretation Our data on cases as well as their infected and uninfected close contacts provide key insights into SARS-CoV-2 epidemiology. This work shows that heightened surveillance and isolation, particularly contact tracing, reduces the time cases are infectious in the community, thereby reducing R. Its overall impact, however, is uncertain and highly dependent on the number of asymptomatic cases. We further show that children are at similar risk of infection as the general population, though less likely to have severe symptoms; hence should be considered in analyses of transmission and control.</jats:p>",2020-03-04,"['Qifang Bi', 'Yongsheng Wu', 'Shujiang Mei', 'Chenfei Ye', 'Xuan Zou', 'Zhen Zhang', 'Xiaojian Liu', 'Lan Wei', 'Shaun A Truelove', 'Tong Zhang', 'Wei Gao', 'Cong Cheng', 'Xiujuan Tang', 'Xiaoliang Wu', 'Yu Wu', 'Binbin Sun', 'Suli Huang', 'Yu Sun', 'Juncen Zhang', 'Ting Ma', 'Justin Lessler', 'Teijian Feng']",,,,True
e1008925754f127b74ab07e83fd64c0260b980a2,medrxiv,Effect of non-pharmaceutical interventions for containing the COVID-19 outbreak in China,doi.org/10.1101/2020.03.03.20029843,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: The COVID-19 outbreak containment strategies in China based on non-pharmaceutical interventions (NPIs) appear to be effective. Quantitative research is still needed however to assess the efficacy of different candidate NPIs and their timings to guide ongoing and future responses to epidemics of this emerging disease across the World. Methods:  We built a travel network-based susceptible-exposed-infectious-removed (SEIR) model to simulate the outbreak across cities in mainland China. We used epidemiological parameters estimated for the early stage of outbreak in Wuhan to parameterise the transmission before NPIs were implemented. To quantify the relative effect of various NPIs, daily changes of delay from illness onset to the first reported case in each county were used as a proxy for the improvement of case identification and isolation across the outbreak. Historical and near-real time human movement data, obtained from Baidu location-based service, were used to derive the intensity of travel restrictions and contact reductions across China. The model and outputs were validated using daily reported case numbers, with a series of sensitivity analyses conducted. Results: We estimated that there were a total of 114,325 COVID-19 cases (interquartile range [IQR] 76,776 - 164,576) in mainland China as of February 29, 2020, and these were highly correlated (p&lt;0.001, R2=0.86) with reported incidence. Without NPIs, the number of COVID-19 cases would likely have shown a 67-fold increase (IQR: 44 - 94), with the effectiveness of different interventions varying. The early detection and isolation of cases was estimated to prevent more infections than travel restrictions and contact reductions, but integrated NPIs would achieve the strongest and most rapid effect. If NPIs could have been conducted one week, two weeks, or three weeks earlier in China, cases could have been reduced by 66%, 86%, and 95%, respectively, together with significantly reducing the number of affected areas. However, if NPIs were conducted one week, two weeks, or three weeks later, the number of cases could have shown a 3-fold, 7-fold, and 18-fold increase across China, respectively. Results also suggest that the social distancing intervention should be continued for the next few months in China to prevent case numbers increasing again after travel restrictions were lifted on February 17, 2020. Conclusion: The NPIs deployed in China appear to be effectively containing the COVID-19 outbreak, but the efficacy of the different interventions varied, with the early case detection and contact reduction being the most effective. Moreover, deploying the NPIs early is also important to prevent further spread. Early and integrated NPI strategies should be prepared, adopted and adjusted to minimize health, social and economic impacts in affected regions around the World.</jats:p>",2020-03-06,"['Shengjie Lai', 'Nick W Ruktanonchai', 'Liangcai Zhou', 'Olivia Prosper', 'Wei Luo', 'Jessica R Floyd', 'Amy Wesolowski', 'Mauricio Santillana', 'Chi Zhang', 'Xiangjun Du', 'Hongjie Yu', 'Andrew J Tatem']",,,,True
3028628066ec2401f3981f4e70c5b1acd4cef573,medrxiv,Transmission interval estimates suggest pre-symptomatic spread of COVID-19,doi.org/10.1101/2020.03.03.20029983,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: As the COVID-19 epidemic is spreading, incoming data allows us to quantify values of key variables that determine the transmission and the effort required to control the epidemic. We determine the incubation period and serial interval distribution for transmission clusters in Singapore and in Tianjin. We infer the basic reproduction number and identify the extent of pre-symptomatic transmission. Methods:  We collected outbreak information from Singapore and Tianjin,  China,  reported from Jan.19-Feb.26 and Jan.21-Feb.27, respectively. We estimated incubation periods and serial intervals in both populations. Results: The mean incubation period was 7.1 (6.13, 8.25) days for Singapore and 9 (7.92, 10.2)days for Tianjin. Both datasets had shorter incubation periods for earlier-occurring cases. The mean serial interval was 4.56 (2.69, 6.42) days for Singapore and 4.22 (3.43, 5.01) for Tianjin. We inferred that early in the outbreaks, infection was transmitted on average 2.55 and 2.89days before symptom onset (Singapore, Tianjin). The estimated basic reproduction number for Singapore was 1.97 (1.45, 2.48) secondary cases per infective; for Tianjin it was 1.87 (1.65,2.09) secondary cases per infective. Conclusions: Estimated serial intervals are shorter than incubation periods in both Singapore and Tianjin, suggesting that pre-symptomatic transmission is occurring.  Shorter serial intervals lead to lower estimates of R0, which suggest that half of all secondary infections should be prevented to control spread.</jats:p>",2020-03-06,"['Lauren Tindale', 'Michelle Coombe', 'Jessica E Stockdale', 'Emma Garlock', 'Wing Yin Venus Lau', 'Manu Saraswat', 'Yen-Hsiang Brian Lee', 'Louxin Zhang', 'Dongxuan Chen', 'Jacco Wallinga', 'Caroline Colijn']",,,,True
462cbb326ccd8587cae7a3538c8c6712d9013698,medrxiv,"Epidemiological and clinical features of 291 cases with coronavirus disease 2019 in areas adjacent to Hubei, China: a double-center observational study",doi.org/10.1101/2020.03.03.20030353,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Abstract Background: The clinical outcomes of COVID-19 patients in Hubei and other areas are different. We aim to investigate the epidemiological and clinical characteristics of patient with COVID-19 in Hunan which is adjacent to Hubei. Methods: In this double-center, observational study, we recruited all consecutive patients with laboratory confirmed COVID-19 from January 23 to February 14, 2020 in two designated hospitals in Hunan province, China. Epidemiological and clinical data from patients' electronic medical records were collected and compared between mild, moderate and severe/critical group in detail. Clinical outcomes were followed up to February 20, 2020.  Findings: 291 patients with COVID-19 were categorized into mild group (10.0%), moderate group (72.8%) and severe/critical group (17.2%). The median age of all patients was 46 years (49.8% were male). 86.6% patients had an indirect exposure history. The proportion of patients that had been to Wuhan in severe/critical group (48.0% vs 17.2%, p=0.006) and moderate group (43.4% vs 17.2%, p=0.007) were higher than mild group. Fever (68.7%), cough (60.5%), and fatigue (31.6%) were common symptoms especially for severe and critical patients. Typical lung imaging finding were bilateral and unilateral ground glass opacity or consolidation. Leukopenia, lymphopenia and eosinopenia occurred in 36.1%, 22.7% and 50.2% patients respectively. Increased fibrinogen was detected in 45 of 58 (77.6%) patients with available results. 29 of 44 (65.9%) or 22 of 40 (55.0%) patients were positive in Mycoplasma pneumonia or Chlamydia pneumonia antibody test respectively. Compared with mild or moderate group, severe/critical group had a relative higher level of neutrophil, Neutrophil-to-Lymphocyte Ratio, h-CRP, ESR, CK, CK-MB, LDH, D-dimer, and a lower level of lymphocyte, eosinophils, platelet, HDL and sodium (all p&lt;0.01). Most patients received antiviral therapy and Chinese Medicine therapy. As of February 20, 2020, 159 (54.6%) patients were discharged and 2 (0.7%) patients died during hospitalization. The median length of hospital stay in discharged patients was 12 days (IQR: 10-15).  Interpretation: The epidemiological and clinical characteristics of COVID-19 patients in Hunan is different from patients in Wuhan. The proportion of patients that had been to Wuhan in severe/critical group and moderate group were higher than mild group. Laboratory and imaging examination can assist in the diagnosis and classification of COVID-19 patients.</jats:p>",2020-03-06,"['Xu Chen', 'Fang Zheng', 'Yanhua Qing', 'Shuizi Ding', 'Danhui Yang', 'Cheng Lei', 'Zhilan Yin', 'Xianglin Zhou', 'Dixuan Jiang', 'Qi Zuo', 'Jun He', 'Jianlei Lv', 'Ping Chen', 'Yan Chen', 'Hong Peng', 'Honghui Li', 'Yuanlin Xie', 'Jiyang Liu', 'Zhiguo Zhou', 'Hong Luo']",,,,True
e560eb28bb3f35099d2632f80adaa14436516474,medrxiv,Restoration of leukomonocyte counts is associated with viral clearance in COVID-19 hospitalized patients,doi.org/10.1101/2020.03.03.20030437,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Viral clearance is one important indicator for the recovery of SARS-CoV-2 infected patients. Suboptimal T and B cell responses can delay viral clearance in MERS and SARS patients. The role of leukomonocytes in viral clearance of COVID-19 patients is not yet well defined.Methods: From January 26 to February 28, 2020, an observational study was launched at Zhongnan Hospital of Wuhan University, Wuhan, China. We enrolled 25 laboratory-confirmed COVID-19 patients, whose throat-swab specimens were tested positive for SARS-CoV-2 infection by qRT-PCR. We comprehensively analyzed clinical records, counts of lymphocyte subsets including CD3+, CD4+, CD8+ T cells, B cells and NK cells in the patients who successfully cleared SARS-CoV-2, and compared to those that failed to, after a standardized treatment of 8-14 days. Findings: In 25 enrolled COVID-19 patients, lymphopeniawas a common feature. After the treatment, 14 patients were tested negative for SARS-CoV-2. The patients that cleared the infection had restored the numbers of CD3+, CD4+, CD8+ T cellsand B cells as compared to the still viral RNA positive patients, while the recovered patients had a higher count of leukomonocytes. Conclusions: By comparison of leukomonocytes counts in COVID-19 patients at different stages of the disease, we found that CD3+, CD4+, CD8+ T cells and B cells appear to play important roles in viral clearance. The restoration of leukomonocytes counts from peripheral blood can be used as prognosis for the recovery of an COVID-19 infection. We propose that restoration of leukomonocytes counts can be added to the COVID-19 diagnostic guidanceas a criterion for releasing and discharging patients.</jats:p>",2020-03-06,"['Xiaoping Chen', 'Jiaxin Ling', 'Pingzheng Mo', 'Yongxi Zhang', 'Qunqun Jiang', 'Zhiyong Ma', 'Qian Cao', 'Wenjia Hu', 'Shi Zou', 'Liangjun Chen', 'Lei Yao', 'Mingqi Luo', 'Tielong Chen', 'Liping Deng', 'Ke Liang', 'Shihui Song', 'Rongrong Yang', 'Ruiying Zheng', 'Shicheng Gao', 'Xien Gui', 'Hengning Ke', 'Wei Hou', 'Åke Lundkvist', 'Yong Xiong']",,,,True
46503fb7ba542dcdfb7c0e27e5edae0586c4873c,medrxiv,Modelling-based evaluation of the effect of quarantine control by the Chinese government in the coronavirus disease 2019 outbreak,doi.org/10.1101/2020.03.03.20030445,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The novel coronavirus disease 2019 (COVID-19) epidemic, which was first identified in Wuhan, China in December 2019, has rapidly spread all over China and across the world. By the end of February 2020, the epidemic outside Hubei province in China has been well controlled, yet the next wave of transmission in other countries may have just begun. A retrospective modeling of the transmission dynamics would provide insights into the epidemiological characteristics of the disease and evaluation of the effectiveness of the strict measures that have been taken by central and local governments of China. Using a refined susceptible-exposed-infectious-removed (SEIR) transmission model and a new strategy of model fitting, we were able to estimate model parameters in a dynamic manner. The resulting parameter estimation can well reflect the prevention policy scenarios. Our simulation results with different degrees of government control suggest that the strictly enforced quarantine and travel ban have significantly decreased the otherwise uncontrollable spread of the disease. Our results suggest similar measures should be considered by other countries that are of high risk of COVID-19 outbreak.</jats:p>",2020-03-06,"['Xinkai Zhou', 'Zhigui Wu', 'Ranran Yu', 'Shanni Cao', 'Wen Fang', 'Zhen Jiang', 'Fang Yuan', 'Chao Yan', 'Dijun Chen']",,,,False
9701a8c529cd8c18124da4cd61c1165a64b50281,medrxiv,"Evolving Epidemiology and Impact of Non-pharmaceutical Interventions on the Outbreak of Coronavirus Disease 2019 in Wuhan, China",doi.org/10.1101/2020.03.03.20030593,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>BACKGROUND We described the epidemiological features of the coronavirus disease 2019 (Covid-19) outbreak, and evaluated the impact of non-pharmaceutical interventions on the epidemic in Wuhan, China.  METHODS Individual-level data on 25,961 laboratory-confirmed Covid-19 cases reported through February 18, 2020 were extracted from the municipal Notifiable Disease Report System. Based on key events and interventions, we divided the epidemic into four periods: before January 11, January 11-22, January 23 - February 1, and February 2-18. We compared epidemiological characteristics across periods and different demographic groups. We developed a susceptible-exposed-infectious-recovered model to study the epidemic and evaluate the impact of interventions.   RESULTS The median age of the cases was 57 years and 50.3% were women. The attack rate peaked in the third period and substantially declined afterwards across geographic regions, sex and age groups, except for children (age &lt;20) whose attack rate continued to increase. Healthcare workers and elderly people had higher attack rates and severity risk increased with age. The effective reproductive number dropped from 3.86 (95% credible interval 3.74 to 3.97) before interventions to 0.32 (0.28 to 0.37) post interventions. The interventions were estimated to prevent 94.5% (93.7 to 95.2%) infections till February 18. We found that at least 59% of infected cases were unascertained in Wuhan, potentially including asymptomatic and mild-symptomatic cases.  CONCLUSIONS	 Considerable countermeasures have effectively controlled the Covid-19 outbreak in Wuhan. Special efforts are needed to protect vulnerable populations, including healthcare workers, elderly and children. Estimation of unascertained cases has important implications on continuing surveillance and interventions.</jats:p>",2020-03-06,"['Chaolong Wang', 'Li Liu', 'Xingjie Hao', 'Huan Guo', 'Qi Wang', 'Jiao Huang', 'Na He', 'Hongjie Yu', 'Xihong Lin', 'An Pan', 'Sheng Wei', 'Tangchun Wu']",,,,True
9c33486a49de4aea64ce61c0a2c21a88c316b6a8,medrxiv,SOCRATES: An online tool leveraging a social contact data sharing initiative to assess mitigation strategies for COVID-19,doi.org/10.1101/2020.03.03.20030627,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: Establishing a social contact data sharing initiative and an online tool to assess mitigation strategies for COVID-19. Results: Using our online tool and the available social contact data, we illustrate that social distancing could have a considerable impact on reducing transmission for COVID-19. The effect itself depends on assumptions made about disease-specific characteristics and the choice of intervention(s).  Keywords: Social contact data, Data sharing initiative, User interface.</jats:p>",2020-03-06,"['LANDER WILLEM', 'THANG VAN HOANG', 'SEBASTIAN FUNK', 'PIETRO COLETTI', 'PHILIPPPE BEUTELS', 'NIEL HENS']",,,,True
594d23a412649df7dbfef5347a2a0c208ed4417d,medrxiv,Immunodepletion with Hypoxemia: A Potential High Risk Subtype of Coronavirus Disease 2019,doi.org/10.1101/2020.03.03.20030650,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background The outbreak of COVID-2019 is becoming a global public health emergency. Although its basic clinical features have been reported, the dynamic characteristics of immune system in COVID-2019 patients, especially those critical patients with refractory hypoxemia, are not yet well understood. We aim to describe the dynamic characteristics of immune system in 3 critical patients with refractory hypoxemia, and discuss the relationship between hypoxemia severity and immune cell levels, and the changes of gut microbes of COVID-2019 patient. Methods This is a retrospective study from 3 patients with 2019-nCoV infection admitted to Renmin Hospital of Wuhan University, a COVID-2019 designated hospital in Wuhan, from January 31 to February 6, 2020. All patients were diagnosed and classified based on the Diagnosis and Treatment of New Coronavirus Pneumonia (6th edition) published by the National Health Commission of China4. We recorded the epidemiological history, demographic features, clinical characteristics, symptoms and signs, treatment and clinical outcome in detail. Blood samples were collected and we determined the expression levels of immune cells (CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD16+56+ NK cells) in different time points. Nanopore Targeted Sequencing was used to determine the alterations of gut microbiota homeostasis. Results Apart from the clinical features described previously4, we found that four patients had decreased immune cells and refractory hypoxemia during the hospitalization, and the severity of hypoxemia was strongly correlated to the expression levels of immune cells. Additionally, we found that the proportion of probiotics was significantly reduced, such as Bifidobacterium, Lactobacillus, and Eubacterium, and the proportion of conditioned pathogenic bacteria was significantly increased, such as Corynebacterium of Actinobacteria and Ruthenibacterium of Firmicutes. Notably, all patients died. Conclusions We discussed the dynamic characteristics of host immune system and the imbalance of gut microbiota in 3 critical patients with COVID-2019. Hypoxemia severity was closely related with host immune cell levels, and the vicious circle between immune disorder and gut microbiota imbalance may be a high risk of fatal pneumonia. To the best of our knowledge, this is the first study which revealing that immunodepletion with refractory hypoxemia is a potential high risk subtype of COVID-2019 and the vicious circle between immune disorder and gut dysbiosis may be a high risk of fatal pneumonia.</jats:p>",2020-03-06,"['Lilei Yu', 'Yongqing Tong', 'Gaigai Shen', 'Aisi Fu', 'Yanqiu Lai', 'Xiaoya Zhou', 'Yuan Yuan', 'Yuhong Wang', 'Yuchen Pan', 'Zhiyao Yu', 'Yan Li', 'Tiangang Liu', 'Hong Jiang']",,,,True
f879c69d61f14d7efc51023258d1361bc681d403,medrxiv,"Clinical findings in critical ill patients infected with SARS-Cov-2 in Guangdong Province, China: a multi-center, retrospective, observational study",doi.org/10.1101/2020.03.03.20030668,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Abstract  Background In December 2019, human infection with a novel coronavirus, known as SARS-CoV-2, was identified in Wuhan, China. The mortality of critical illness was high in Wuhan. Information about critically ill patients with SARS-CoV-2 infection outside of Wuhan is scarce. We aimed to provide the clinical features, treatment, and prognosis of the critically ill patients with SARS-CoV-2 infection in Guangdong Province. Methods In this multi-centered, retrospective, observational study, we enrolled critically ill patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) in Guangdong Province. Demographic data, symptoms, laboratory findings, comorbidities, treatments, and prognosis were collected. Data were compared between patients with and without intubation.  Results Forty-five critically ill patients with SARS-CoV-2 pneumonia were identified in 7 ICUs in Guangdong Province. The mean age was 56.7 years, and 29 patients (64.4%) were men. The most common symptoms at the onset of illness were high fever and cough. Majority of patients presented with lymphopenia and elevated lactate dehydrogenase. Treatment with antiviral drugs was initiated in all the patients. Thirty-seven patients (82.2%) had developed acute respiratory distress syndrome, and 13 (28.9%) septic shock. A total of 20 (44.4%) patients required intubation and 9 (20%) required extracorporeal membrane oxygenation. As of February 28th 2020, only one patient (2.2%) had died and half of them had discharged of ICU. Conclusions Infection with SARS-CoV-2 in critical illness is characterized by fever, lymphopenia, acute respiratory failure and multiple organ dysfunction. Compared with critically ill patients infected with SARS-CoV-2 in Wuhan, the mortality of critically ill patients in Guangdong Province was relatively low. These data provide some general understandings and experience for the critical patients with SARS-CoV-2 outside of Wuhan.</jats:p>",2020-03-06,"['Yonghao Xu', 'Zhiheng Xu', 'Xuesong Liu', 'Lihua Cai', 'Haichong Zheng', 'Yongbo Huang', 'Lixin Zhou', 'Linxi Huang', 'Yun Lin', 'Liehua Deng', 'Jianwei Li', 'Sibei Chen', 'Dongdong Liu', 'Zhimin Lin', 'Liang Zhou', 'Weiqun He', 'Xiaoqing Liu', 'Yimin Li']",,,,True
e0a53c258ee0483666329ccab591c0753ff49531,medrxiv,Key Points of Clinical and CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV) Imported Pneumonia Based On 21 Cases Analysis,doi.org/10.1101/2020.03.03.20030775,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background and Objective: WHO Director-General declared that the 2019-nCoV outbreak constitutes a Public Health Emergency of International Concern,and the outbreak is still on-going.Chest CT had been a key component of the diagnostic workup for patients with suspected infection. In this retrospective study, we attempt to summarize and analyze the chest CT features of 2019-nCov infections, and to identify the typical features to improved the diagnostic accuracy of new coronavirus pneumonia (NCP). Methods:Chest CT scans and Clinical data of 21 patients confirmed NCP in our hospital were enrolled.These patients were divided into mild and sever group according to clinical manifestations described by the 6th clinical practice guideline of NCP in China. Main clinical and chest CT features were analyzed and identify. Results: Fever (85.7%) and cough (80.9%) were the two main symptoms of NCP patients.More significantly higher incidence (85.7%) of shortness of breath in the severe cases. Multiple lesions in both lungs and with incidence of GGO(100%),vascular enlargement (76.5%) and cobblestone/reticular pattern(70.6%) were the major feature.The incidence of consolidation, mixed pattern and vascular enlargement features were up to 100% in the severe group, significantly higher than that of patients in mild group. In addition, the incidence of air-bronchogram, dilated bronchi with thickened wall and fibrosis in the severe group was significantly higher than that in the mild group. Conclusions: Fever and cough are the typical clinical features of NCP patients, and chest CT mainly manifested as multiple lesions in both lungs, often accompanied by GGO, vascular enlargement and cobblestone/reticular pattern.Changes in these main CT features can indicate development of the disease.</jats:p>",2020-03-06,"['wenxiu Wu', 'zhifeng xu', 'yabin Jin', 'aizhen Pan']",,,,True
0ab795fc615df6457551a8e231dce1f268eef9d2,medrxiv,Caution: The clinical characteristics of COVID-19 patients at admission are changing,doi.org/10.1101/2020.03.03.20030833,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background  With the emergence of 4rd generation transmission, the prevention and treatment of the novel coronavirus disease 2019 (COVID-19) has entered a new period. We aimed to report several changes in the clinical characteristics at admission of patients with COVID-19. Methods Clinical records and laboratory results of patients suffering from COVID-19 were retrospectively reviewed and matched with the admission dates to analyze the changes in characteristics at the onset of illness. Results  Of the 89 affected patients, 31 [34.8%] patients were admitted from January 16 to 22, and 58 [65.2%] were admitted from January 23 to 29. Patients were admitted with more systemic symptoms, such as fever (21 [67.7%] of 31), fatigue (13 [41.9%] of 31), and myalgia (7 [22.6%] of 31), before January 23. More patients (10 [32.3%] of 31) admitted before January 23 had a small amount of sputum production compared with a smaller proportion (4 [6.9%] of 58) of the patients admitted after January 23. Other symptoms, such as cough, nausea, diarrhea, and chest tightness, were not significantly different between the two groups. In addition, the group admitted before January 23 had a larger proportion of patients with reduced lymphocyte (13 [54.2%] of 24), CD3 (11 [54.4%] of 21), and CD8 (9 [42.9%] of 21) counts and elevated serum amyloid A (SAA, 18 [75%] of 24).  Conclusions The initial symptoms of recently infected patients seem more insidious, indicating that the new coronavirus may gradually evolve into a virus similar to influenza and latent in asymptomatic carriers for a long time.</jats:p>",2020-03-06,"['Zhaowei Chen', 'Jijia Hu', 'Zongwei Zhang', 'Shan Jiang', 'Tao Wang', 'Zhengli Shi', 'Zhan Zhang']",,,,True
5bb89950ec5a06e2b7f69b2a9c4213dda19b1ab0,medrxiv,Prediction of New Coronavirus Infection Based on a Modified SEIR Model,doi.org/10.1101/2020.03.03.20030858,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>BACKGROUND The outbreak of the new coronavirus infection in Wuhan City, Hubei Province in December 2019, poses a huge threat to China and even global public health security. Respiratory droplets and contact transmission are the main routes of transmission of new coronaviruses. Compared with SARS and Ebola viruses, new coronavirus infections are infectious during the incubation period. Traditional SEIR (susceptibility-exposure-infection-Removal) There are some differences in conditions for the prediction of the epidemic trend of new coronavirus infection. The outbreak of the new coronavirus infection coincided with the Spring Festival before and after the Chinese Spring Festival.It is necessary to make appropriate optimization and amendments to the traditional model to meet the actual evolution of the epidemic situation.   METHODS The traditional SEIR model assumes that the virus-infected person is not infectious during the incubation period and that the infected person did not take isolation measures during the illness. The transmission of the new coronavirus no longer meets the basic assumptions of the classical kinetic system. Therefore, this article first establishes a modified SEIR model. Predict and analyze the changing trend of the epidemic situation, then estimate the parameters involved in the infection dynamics model, and then use Matlab to simulate the established dynamic equations based on public data and analyze the results. Recommendations for universal prevention and control of infectious diseases.  RESULTS The first case of new coronavirus infection was confirmed in Wuhan on December 8, 2019. When Wuhan City took no action, assuming the average daily number of contacts per infected person k = 5, the number of infected persons will reach about 2,384,803 people; If wuhan adopts the measures of sealing the city on January 22, 2020, under the premise of k=2, the number of infected people decreases by 19,773 compared with that on January 23, and there is no significant change in the time when the number of infected people reaches the peak. Under the premise of k = 1, the number of infected persons was reduced by 14,330 compared with the closure on January 23, and the time to reach the peak of the number of infected persons was reduced by 2 days. If Wuhan City is closed for one day, the number of infected persons will increase from 106,145 to 130,626 under the premise of k = 2; the number of infected persons will increase from 74,369 to 92,010 under the premise of k = 1.    CONCLUSIONS  Comparing the number of confirmed diagnoses actually notified by the department with the number of infected people obtained from the simulation of the model, it can be seen that the city closure measures adopted by the Wuhan Municipal Government on January 23 and the first-level response measures adopted by the country are effective for the epidemic Prevention and control play a vital role. Wearing a mask when going out and avoiding close contact with people can effectively reduce the infection rate.</jats:p>",2020-03-06,"['Zhou Tang', 'Xianbin Li', 'Houqiang Li']",,,,True
df00ddc0f2a812da876684c9d5d21c8082cacd68,medrxiv,Psychological impact of the coronavirus disease 2019 (COVID-19) outbreak on healthcare workers in China,doi.org/10.1101/2020.03.03.20030874,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Introduction Since the outbreak of coronavirus disease 2019 (COVID-19), more than 3000 (including clinical diagnosis) healthcare workers (HCWs) have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China. This study is aimed to investigate the risk perception and immediate psychological state of HCWs in the early stage of the COVID-19 epidemic.  Methods This study utilized a cross-sectional survey designed on a convenient sample of 4357 HCWs in China. Its data were collected using anonymous structured questionnaires distributed through social software. 6 questions were set to evaluate the participants' risk perception of COVID-19, and a General Health Questionnaire was used to identify the participants' immediate psychological status. Descriptive statistics were used for data analysis. Risk perception and psychological status were compared by demographic characteristics and COVID-19 exposure experiences. Result A total of 4,600 questionnaires were distributed, and 4,357 qualified ones (94.7%) were collected. The main concerns of HCWs are: infection of colleagues (72.5%), infection of family members (63.9%), protective measures (52.3%) and medical violence (48.5%). And 39.1% of the HCWs had psychological distress, especially working in Wuhan, participating in frontline treatments, having been isolated and having family members or colleagues infected. Conclusions The finding indicating that, faced with the COVID-19 epidemic, HCWs, especially in Wuhan, were worried about the risks of infection and protective measures, resulting in psychological distress, so further actions should be taken.</jats:p>",2020-03-06,"['Yuhong Dai', 'Guangyuan Hu', 'Huihua Xiong', 'Hong Qiu', 'Xianglin Yuan']",,,,False
3afd5fba7dc182ddfa769c0d766134b525581005,medrxiv,"Transmission and clinical characteristics of coronavirus disease 2019 in 104 outside-Wuhan patients, China",doi.org/10.1101/2020.03.04.20026005,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Cases with coronavirus disease 2019 (COVID-19) emigrated from Wuhan escalated the risk of spreading in other cities. This report focused on the outside-Wuhan patients to assess the transmission and clinical characteristics of this illness. Methods: Contact investigation was conducted on each patient who admitted to the assigned hospitals in Hunan Province (geographically adjacent to Wuhan) from Jan 22, 2020 to Feb 12, 2020. Demographic, clinical, laboratory and radiological characteristics, medication therapy and outcomes were collected and analyzed. Patients were confirmed by PCR test. Results: Of the 104 patients, 48 (46.15%) were imported cases and 56 (53.85%) were indigenous cases; 93 (89.42%) had a definite contact history with infections. Family clusters were the major body of patients. Transmission along the chain of 3 &amp;ldquo:generations” was observed. Mean age was 43 (rang, 8-84) years (including 3 children) and 49 (47.12%) were male. Most patients had typical symptoms, 5 asymptomatic infections were found and 2 of them infected their relatives. The median incubation period was 6 (rang, 1-32) days, of 8 patients ranged from 18 to 32 days. Just 9 of 16 severe patients required ICU care. Until Feb 12, 2020, 40 (38.46%) discharged and 1 (0.96%) died. For the antiviral treatment, 80 (76.92%) patients received traditional Chinese medicine therapy. Conclusions: Family but not community transmission occupied the main body of infections in the two centers. Asymptomatic transmission demonstrated here warned us that it may bring more risk to the spread of COVID-19. The incubation period of 8 patients exceeded 14 days.</jats:p>",2020-03-06,"['Chengfeng Qiu', 'Qian Xiao', 'Xin Liao', 'Ziwei Deng', 'Huiwen Liu', 'Yuanlu Shu', 'Dinghui Zhou', 'Ye Deng', 'Hongqiang Wang', 'Xiang Zhao', 'Jianliang Zhou', 'Jin Wang', 'Zhihua Shi', 'Long Da']",,,,True
3deb6393bd43f440a69c84da9ed61986b1781d36,medrxiv,Nanopore target sequencing for accurate and comprehensive detection of SARS-CoV-2 and other respiratory viruses,doi.org/10.1101/2020.03.04.20029538,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The ongoing novel coronavirus pneumonia COVID-19 outbreak in Wuhan, China, has engendered numerous cases of infection and death. COVID-19 diagnosis relies upon nucleic acid detection; however, current recommended methods exhibit high false-negative rates, low sensitivity, and cannot identify other respiratory virus infections, thereby resulting patient misdiagnosis and impeding epidemic containment. Combining the advantages of target amplification and long-read, real-time nanopore sequencing, we developed nanopore target sequencing (NTS) to detect SARS-CoV-2 and other respiratory viruses simultaneously within 6-10 h. Parallel testing with approved qPCR kits of SARS-CoV-2 and NTS using 61 nucleic acid samples from suspected COVID-19 cases confirmed that NTS identified more infected patients as positive, and could also monitor for mutated nucleic acid sequence or other respiratory virus infection in the test sample. NTS is thus suitable for contemporary COVID-19 diagnosis; moreover, this platform can be further extended for diagnosing other viruses or pathogens.</jats:p>",2020-03-06,"['Ming Wang', 'Aisi Fu', 'Ben Hu', 'Yongqing Tong', 'Ran Liu', 'Jiashuang Gu', 'Jianghao Liu', 'Wen Jiang', 'Gaigai Shen', 'Wanxu Zhao', 'Dong Men', 'Lilei Yu', 'Zixin Deng', 'Yan Li', 'Tiangang Liu']",,,,True
3fe2552d3d8e6c9ead2c41e30fbb69e917277f53,medrxiv,"Clinical Features of Patients Infected with the 2019 Novel Coronavirus (COVID-19) in Shanghai, China",doi.org/10.1101/2020.03.04.20030395,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Since mid-December 2019, a cluster of pneumonia-like diseases caused by a novel coronavirus, now designated COVID-19 by the WHO, emerged in Wuhan city and rapidly spread throughout China. Here we identify the clinical characteristics of COVID-19 in a cohort of patients in Shanghai.  Methods: Cases were confirmed by real-time RT-PCR and were analysed for demographic, clinical, laboratory and radiological features.  Results: Of 198 patients, the median duration from disease onset to hospital admission was 4 days. The mean age of the patients was 50.1 years, and 51.0% patients were male. The most common symptom was fever. Less than half of the patients presented with respiratory systems including cough, sputum production, itchy or sore throat, shortness of breath, and chest congestion. 5.6% patients had diarrhoea. On admission, T lymphocytes were decreased in 45.8% patients. Ground glass opacity was the most common radiological finding on chest computed tomography. 9.6% were admitted to the ICU because of the development of organ dysfunction. Compared with patients not treated in ICU, patients treated in the ICU were older, had longer waiting time to admission, fever over 38.5o C, dyspnoea, reduced T lymphocytes, elevated neutrophils and organ failure. Conclusions: In this single centre cohort of COVID-19 patients, the most common symptom was fever, and the most common laboratory abnormality was decreased blood T cell counts. Older age, male, fever over 38.5oC, symptoms of dyspnoea, and underlying comorbidity, were the risk factors most associated with severity of disease. Key words: 2019 novel coronavirus; acute respiratory infection; risk factors for disease severity</jats:p>",2020-03-06,"['Min Cao', 'Dandan Zhang', 'Youhua Wang', 'Yunfei Lu', 'Xiangdong Zhu', 'Ying Li', 'Honghao Xue', 'Yunxiao Lin', 'Min Zhang', 'Yiguo Sun', 'Zongguo Yang', 'Jia Shi', 'Yi Wang', 'Chang Zhou', 'Yidan Dong', 'Ping Liu', 'Steven M Dudek', 'Zhen Xiao', 'Hongzhou Lu', 'Longping Peng']",,,,True
4380f0251c595d6cb551e643198d2dacd3c6746c,medrxiv,Serological detection of 2019-nCoV respond to the epidemic: A useful complement to nucleic acid testing,doi.org/10.1101/2020.03.04.20030916,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Corona Virus Disease 2019 (COVID-19) has spread rapidly to more than 70 countries and regions overseas and over 80000 cases have been infected, resulting in more than three thousand deaths. Rapid diagnosis of patients remains a bottleneck in containing the progress of the epidemic. We used automated chemiluminescent immunoassay to detect serum IgM and IgG antibodies to 2019-nCoV of 736 subjects. COVID-19 patients were becoming reactive(positive) for specific antibodies from 7-12 days after the onset of morbidity. Specific IgM and IgG increased with the progression of the disease. The areas under the ROC curves of IgM and IgG were 0.988 and 1.000, respectively. Specific antibody detection has good sensitivity and specificity. Detection of specific antibodies in patients with fever can be a good distinction between COVID-19 and other diseases, so as to be a complement to nucleic acid diagnosis to early diagnosis of suspected cases.</jats:p>",2020-03-06,"['Jin Zhang', 'Jianhua Liu', 'Na Li', 'Yong Liu', 'Rui Ye', 'Xiaosong Qin', 'Rui Zheng']",,,,True
e066fdbb4a9338a57477424cb66fd4d75b2fd66d,medrxiv,Comparison of severe and non-severe COVID-19 pneumonia: review and meta-analysis,doi.org/10.1101/2020.03.04.20030965,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: To compare the difference between severe and non-severe COVID-19 pneumonia and figure out the potential symptoms lead to severity. Methods: Articles from PubMed, Embase, Cochrane database, and google up-to 24 February 2020 were systematically reviewed. Eighteen Literatures were identified with cases of COVID-19 pneumonia. The extracted data includes clinical symptoms, age, gender, sample size and region et al were systematic reviewed and meta analyzed. Results: 14 eligible studies including 1,424 patients were analyzed. Symptoms like fever (89.2%), cough (67.2%), fatigue (43.6%) were common, dizziness, hemoptysis, abdominal pain and conjunctival congestion/conjunctivitis were rare. Polypnea/dyspnea in severe patients were significantly higher than non-severe (42.7% vs.16.3%, P&lt;0.0001). Fever and diarrhea were higher in severe patients(p=0.0374and0.0267). Further meta-analysis showed incidence of fever(OR1.70,95%CI 1.01-2.87), polypnea/dyspnea(OR3.53, 95%CI 1.95-6.38) and diarrhea(OR1.80,95%CI 1.06-3.03) was higher in severe patients, which meant the severe risk of patients with fever, polypnea/dyspnea, diarrhea were 1.70, 3.53, 1.80 times higher than those with no corresponding symptoms.  Conclusions: Fever, cough and fatigue are common symptoms in COVID-19 pneumonia. Compared with non-severe patients, the symptoms as fever, polypnea/dyspnea and diarrhea are potential symptoms lead to severity.</jats:p>",2020-03-09,"['Weiping Ji', 'Jing Zhang', 'Gautam Bishnu', 'Xudong Du', 'Xinxin Chen', 'Hui Xu', 'Xiaoling Guo', 'Zhenzhai Cai', 'Xian Shen']",,,,True
1a12cc7d49d8521bec5d447ebb413cbcf5aca8f4,medrxiv,Study of the mental health status of medical personnel dealing with new coronavirus pneumonia,doi.org/10.1101/2020.03.04.20030973,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: This paper studied the relationship between personality traits and mental health conditions of medical personnel to provide a basis and reference for the implementation of targeted education on mental health. Methods: A self-report inventory, the Symptom Checklist-90 (SCL-90), was used to investigate the mental health status of 548 medical personnel dealing with the new coronavirus pneumonia in eight provinces and cities of China. Results: The overall mean SCL-90 score and mean values of factors (somatization, obsessive-compulsive, anxiety, phobic anxiety, and psychoticism) of the medical personnel were significantly higher than in the norm group (p &lt; 0.05), while their average interpersonal sensitivity score was significantly lower (p &lt; 0.01). In addition, personal factors affecting the mental health status of medical personnel were identified. ( all p &lt; 0.05).  Conclusion: The overall mental health status of medical personnel responding to new coronavirus pneumonia is generally higher than that of the norm group in China. The results of this study should contribute to measures to alleviate the psychological pressures on medical personnel dealing with the new coronavirus epidemic in China</jats:p>",2020-03-06,"['ning sun', 'jun xing', 'jun xu', 'ling shu geng', 'qian yu li']",,,,True
16e7e95862d9430497bb2e0fb6c72ccb9d16a992,medrxiv,Case fatality risk of novel coronavirus diseases 2019 in China,doi.org/10.1101/2020.03.04.20031005,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective The outbreak of novel coronavirus disease 2019 (COVID-19) imposed a substantial health burden in mainland China and remains a global epidemic threat. Our objectives are to assess the case fatality risk (CFR) among COVID-19 patients detected in mainland China, stratified by clinical category and age group. Method We collected individual information on laboratory-confirmed COVID-19 cases from publicly available official sources from December 29, 2019 to February 23, 2020. We explored the risk factors associated with mortality. We used methods accounting for right-censoring and survival analyses to estimate the CFR among detected cases.  Results Of 12,863 cases reported outside Hubei, we obtained individual records for 9,651 cases, including 62 deaths and 1,449 discharged cases. The deceased were significantly older than discharged cases (median age: 77 vs 39 years, p&lt;0.001). 58% (36/62) were male. Older age (OR 1.18 per year; 95%CI: 1.14 to 1.22), being male (OR 2.02; 95%CI: 1.02 to 4.03), and being treated in less developed economic regions (e.g., West and Northeast vs. East, OR 3.93; 95%CI: 1.74 to 8.85) were mortality risk factors. The estimated CFR was 0.89-1.24% among all cases. The fatality risk among critical patients was 2-fold higher than that among severe and critical patients, and 24-fold higher than that among moderate, severe and critical patients. Conclusions Our estimates of CFR based on laboratory-confirmed cases ascertained outside of Hubei suggest that COVID-19 is not as severe as severe acute respiratory syndrome and Middle East respiratory syndrome, but more similar to the mortality risk of 2009 H1N1 influenza pandemic in hospitalized patients. The fatality risk of COVID-19 is higher in males and increases with age. Our study improves the severity assessment of the ongoing epidemic and can inform the COVID-19 outbreak response in China and beyond.</jats:p>",2020-03-06,"['Xiaowei Deng', 'Juan Yang', 'Wei Wang', 'Xiling Wang', 'Jiaxin Zhou', 'Zhiyuan Chen', 'Jing Li', 'Yinzi Chen', 'Han Yan', 'Juanjuan Zhang', 'Yongli Zhang', 'Yan Wang', 'Qi Qiu', 'Hui Gong', 'Xianglin Wei', 'Lili Wang', 'Kaiyuan Sun', 'Peng Wu', 'Marco Ajelli', 'Benjamin J. Cowling', 'Cecile Viboud', 'Hongjie Yu']",,,,False
3e9ae5329eecab16d7c39f1f6dc778cf4a53ee0d,medrxiv,"Clinical characteristics of 101 non-surviving hospitalized patients with COVID-19: A single center, retrospective study",doi.org/10.1101/2020.03.04.20031039,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Abstract Rationale: COVID-19 have deprived many lives in Wuhan, China and caused global concerns. Few studies focused on clinical characteristics non-survivors hospitalized with COVID-19.   Objectives: We aimed to clarify the clinical characteristics of died patients with COVID-19 and tracked the causes of the rapid disease progression and death.  Methods: 101 non-surviving patients with confirmed COVID-19 were included in this retrospective study. Clinical data were collected and compared between non-survivors who died within 3 days and after 3 days of admission. Multivariable regression analysis was used to analyze risk factors associated with rapid disease progression and death. Measurements and Main Results: Among included patients, median age was 71 years (IQR, 59-80), 60 (59.41%) were men. 82 (81.19%) had one or more comorbidities including hypertension (59 [58.42%]), diabetes (22 [21.78%]) etc. 100 (99.01%) suffered respiratory failure, 53 (52.48%) developed acute cardiac injury, acute kidney and liver injury occurred in 23 (22.77%) and 18 (17.82%) patients, respectively. Multivariable regression analysis showed that elevated high sensitivity troponin I (OR 2.68, 95%CI 1.31-5.49, P=0.007), neutrophils (OR 1.14, 95%CI 1.01-1.28, P=0.033) and depressed oxygen saturation (OR 0.94, 95%CI 0.89-0.99, P=0.027) on admission were associated with rapid death of patients with COVID-19. Conclusions: Older patients (&gt;70 years) with comorbidities had a steeply increased risk of death with COVID-19. Respiratory failure, acute cardiac and kidney injury played a crucial role in the death of patients. Elevated high sensitivity troponin, neutrophils and depressed oxygen saturation predicted the rapid death of patients.</jats:p>",2020-03-06,"['Qiao Shi', 'Kailiang Zhao', 'Jia Yu', 'Jiarui Feng', 'Kaiping Zhao', 'Xiaoyi Zhang', 'Xiaoyan Chen', 'Peng Hu', 'Yupu Hong', 'Man Li', 'Fang Liu', 'Chen Chen', 'Weixing Wang']",,,,True
f47af9fe364fd9bac5e061142208d801667c5aca,medrxiv,How to differentiate COVID-19 pneumonia from heart failure with computed tomography at initial medical contact during epidemic period,doi.org/10.1101/2020.03.04.20031047,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>OBJECTIVES To compare chest CT findings in heart failure with those of Corona Virus Disease 2019 (COVID-19) pneumonia. BACKGROUND During epidemic period, chest computed tomography (CT) has been highly recommended for screening patients with suspected COVID-19. However, the comparison of CT imaging between heart failure and COVID-19 pneumonia has not been fully elucidated. METHODS Patients with heart failure (n=12), COVID-19 pneumonia (n=12) and one patient with both diseases were retrospectively enrolled. Clinical information and imaging of chest CT were collected and analyzed.  RESULTS There was no difference of ground glass opacity (GGO), consolidation, crazy paving pattern, lobes affected and septal thickening between heart failure and COVID-19 pneumonia. However, less rounded morphology (8.3% vs. 67%, p=0.003), more peribronchovascular thickening (75% vs. 33%, p=0.041) and fissural thickening (33% vs. 0%, p=0.028), less peripheral distribution (33% vs. 92%, p=0.003) were found in heart failure group than that in COVID-19 group. Importantly, there were also more patients with upper pulmonary vein enlargement (75% vs. 8.3%, p=0.001), subpleural effusion and cardiac enlargement in heart failure group than that in COVID-19 group (50% vs. 0%, p=0.005, separately). Besides, more fibrous lesions were found in COVID-19 group although there was no statistical difference (25% vs. 0%, P=0.064) CONCLUSIONS Although there are some overlaps of CT imaging between heart failure and COVID-19, CT is still a useful tool in differentiating COVID-19 pneumonia.</jats:p>",2020-03-06,"['Zhaowei Zhu', 'Jianjun Tang', 'Xiangping Chai', 'Zhenfei Fang', 'Qiming Liu', 'Xinqun Hu', 'Danyan Xu', 'Jia He', 'Liang Tang', 'Shi Tai', 'Yuzhi Wu', 'Shenghua Zhou']",,,,True
29b3eaeacecf2bfc95b9a493dbb1ba4b2323dd46,medrxiv,"Adjusted age-specific case fatality ratio during the COVID-19 epidemic in Hubei, China, January and February 2020",doi.org/10.1101/2020.03.04.20031104,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The coronavirus disease 2019 (COVID-19) epidemic that originated in Wuhan, China has spread to more than 60 countries. We estimated the age-specific case fatality ratio (CFR) by fitting a transmission model to data from China, accounting for underreporting of cases and the time delay to death. Overall CFR among all infections was 1.6% (1.4-1.8%) and increased considerably for the elderly, highlighting the expected burden for populations with further expansion of the COVID-19 epidemic around the globe.</jats:p>",2020-03-06,"['Julien Riou', 'Anthony Hauser', 'Michel J Counotte', 'Christian L Althaus']",,,,True
734779fad93249a2f6fede6afd10eeff7b37919b,medrxiv,Projecting the transmission dynamics of SARS-CoV-2 through the post-pandemic period,doi.org/10.1101/2020.03.04.20031112,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>There is an urgent need to project how transmission of the novel betacoronavirus SARS-CoV-2 will unfold in coming years. These dynamics will depend on seasonality, the duration of immunity, and the strength of cross-immunity to/from the other human coronaviruses. Using data from the United States, we measured how these factors affect transmission of human betacoronaviruses HCoV-OC43 and HCoV-HKU1. We then built a mathematical model to simulate transmission of SARS-CoV-2 through the year 2025. We project that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after an initial pandemic wave. We summarize the full range of plausible transmission scenarios and identify key data still needed to distinguish between them, most importantly longitudinal serological studies to determine the duration of immunity to SARS-CoV-2.</jats:p>",2020-03-06,"['Stephen M Kissler', 'Christine Tedijanto', 'Edward Goldstein', 'Yonatan H. Grad', 'Marc Lipsitch']",,,,True
924500c41931aa9192ccc820467818297c1679d8,medrxiv,Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection,doi.org/10.1101/2020.03.04.20031120,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>BACKGROUND The coronavirus disease 2019 (COVID-19) is a newly emerged infection from the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Apart from the respiratory system, it is unclear whether SARS-CoV-2 can also directly infect other tissues such as the kidney or induce acute renal failure. METHODS We conducted a retrospective analysis of estimated glomerular filtration rate (eGFR), plasma creatinine, and urea concentrations along with other clinical parameters from 85 patients with laboratory-confirmed COVID-19 admitted to a hospital in Wuhan from January 17, 2020 to March 3, 2020. Kidney tissues from six other patients with postmortem examinations were analyzed by Hematoxylin and Eosin (H&amp;E) and in situ expression of viral nucleocaspid protein (NP) antigen was detected by immunohistochemistry. RESULTS Among these 85 COVID-19 cases, 27.06% (23/85) patients exhibited acute renal failure (ARF), and elder patients (≥ 60 years old) are easier to develop ARF (65.22% vs 24.19%, p&lt; 0.001). Comorbidities of disorders like hypertension and heart failure were more common in patients who developed ARF (69.57% vs 11.29%, p&lt; 0.001). Dynamic observation of eGFR revealed that perished cases have a rapid decrease of eGFR but quickly boosting plasma creatinine and urea. On the other hand, enhancement of eGFR and persistence low level of plasma creatinine and urea was observed in recovery patients following diuretic treatment. H&amp;E staining demonstrated kidney tissues from 6 cases of postmortems have severe acute tubular necrosis but no evidence of glomerular pathology or tubulointerstitial lymphocyte infiltration. Immunohistochemistry showed that SARS-CoV-2 NP antigen was accumulated in kidney tubules.   CONCLUSIONS The development of ARF during the course of disease is an important negative prognostic indicator for survival with COVID-19. SARS-CoV-2 virus directly infects human kidney tubules by thus induces acute tubular damage, ARF and probably also lead to urine transmission.</jats:p>",2020-03-06,"['Bo Diao', 'Zeqing Feng', 'Chenhui Wang', 'Huiming Wang', 'Liang Liu', 'Changsong Wang', 'Rongshuai Wang', 'Ying Liu', 'Yueping Liu', 'Gang Wang', 'Zilin Yuan', 'Yuzhang Wu', 'Yongwen Chen']",,,,True
f40eaec892778166e4f8f8eeb576893e82a591be,medrxiv,The impact of social distancing and epicenter lockdown on the COVID-19 epidemic in mainland China: A data-driven SEIQR model study,doi.org/10.1101/2020.03.04.20031187,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The outbreak of coronavirus disease 2019 (COVID-19) which originated in Wuhan, China, constitutes a public health emergency of international concern with a very high risk of spread and impact at the global level. We developed data-driven susceptible-exposed-infectious-quarantine-recovered (SEIQR) models to simulate the epidemic with the interventions of social distancing and epicenter lockdown. Population migration data combined with officially reported data were used to estimate model parameters, and then calculated the daily exported infected individuals by estimating the daily infected ratio and daily susceptible population size. As of Jan 01, 2020, the estimated initial number of latently infected individuals was 380.1 (95%-CI: 379.8~381.0). With 30 days of substantial social distancing, the reproductive number in Wuhan and Hubei was reduced from 2.2 (95%-CI: 1.4~3.9) to 1.58 (95%-CI: 1.34~2.07), and in other provinces from 2.56 (95%-CI: 2.43~2.63) to 1.65 (95%-CI: 1.56~1.76). We found that earlier intervention of social distancing could significantly limit the epidemic in mainland China. The number of infections could be reduced up to 98.9%, and the number of deaths could be reduced by up to 99.3% as of Feb 23, 2020. However, earlier epicenter lockdown would partially neutralize this favorable effect. Because it would cause in situ deteriorating, which overwhelms the improvement out of the epicenter. To minimize the epidemic size and death, stepwise implementation of social distancing in the epicenter city first, then in the province, and later the whole nation without the epicenter lockdown would be practical and cost-effective.</jats:p>",2020-03-06,"['Yuzhen Zhang', 'Bin Jiang', 'Jiamin Yuan', 'Yanyun Tao']",,,,True
bfed3ce6a6df2d442d96d0cab07d4bc1f2347255,medrxiv,Seattle Flu Study - Swab and Send: Study Protocol for At-Home Surveillance Methods to Estimate the Burden of Respiratory Pathogens on a City-Wide Scale,doi.org/10.1101/2020.03.04.20031211,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Introduction. While seasonal influenza and other respiratory pathogens cause significant morbidity and mortality each year, the community-based burden of these infections remains incompletely understood. Understanding the prevalence, epidemiology, and transmission dynamics of respiratory pathogen infections among community-dwelling individuals is essential during pandemic and epidemic settings and for developing pandemic-preparedness infrastructure.   Methods and Analysis. We present the protocol for a novel, city-wide home-based cross-sectional study in the Seattle Metropolitan area, utilizing rapid delivery systems for self-collection of a nasal swab and return to the laboratory for respiratory pathogen testing. All participation takes place electronically, including recruitment, consent, and data collection. Within 48 hours of participants self-reporting respiratory symptoms, a nasal swab kit is delivered to the household via a courier service. Demographic and illness characteristics are collected at the time of sample collection and recovery and behavioral information collected one week later. Specimens are tested in the laboratory for multiple respiratory pathogens, and results are available on a public website for participants.   Ethics and Dissemination. The study was approved by the University of Washington Institutional Review Board (Protocol #00006181). Results will be disseminated through peer-reviewed publications, talks at conferences, and on the Study Website (www.seattleflu.org).</jats:p>",2020-03-07,"['Ashley E Kim', 'Elisabeth Brandstetter', 'Chelsey Graham', 'Jessica Heimonen', 'Audrey Osterbind', 'Denise J McCulloch', 'Peter D Han', 'Lea M Starita', 'Deborah A Nickerson', 'Margaret M Van de Loo', 'Jennifer Mooney', 'Mark J Rieder', 'Misja Ilcisin', 'Kairsten A Fay', 'Jover Lee', 'Thomas R Sibley', 'Trevor Bedford', 'Janet A Englund', 'Michael Boeckh', 'Helen Y Chu']",,,,True
b696d208705fcb1925693c5f0d118733bb557ea6,medrxiv,"Exploring diseases/traits and blood proteins causally related to expression of ACE2, the putative receptor of 2019-nCov: A Mendelian Randomization analysis",doi.org/10.1101/2020.03.04.20031237,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The novel coronavirus 2019-nCoV has caused major outbreaks in many parts of the world. A better understanding of the pathophysiology of COVID-19 is urgently needed. Clinically, it is important to identify who may be susceptible to infection and identify treatments for the disease. There is good evidence that ACE2 is a receptor for 2019-nCoV, and studies also suggested that high expression of ACE2 may increase susceptibility to infection. Here we conducted a phenome-wide Mendelian randomization (MR) study to prioritize diseases/traits and blood proteins that may be causally linked to ACE2 expression in the lung. Expression data was based on GTEx. We also explored drug candidates whose targets overlapped with the top-ranked proteins in MR analysis, as these drugs could potentially alter ACE2 expression and may be clinically relevant. Notably, MR is much less vulnerable to confounding and reverse causality compared to observational studies. The most consistent finding was a tentative causal association between diabetes-related traits and increased ACE2 expression. Based on one of the largest GWAS on type II diabetes (T2DM) to date (N=898,130), we found that T2DM is causally linked to raised ACE2 expression (beta=0.1835, 95% CI 0.0853-0.2817; p=2.49E-4; GSMR method). Significant associations (at nominal level; p&lt;0.05) was also observed across multiple datasets, with different analytic methods, and for both type I and II diabetes. Other diseases/traits having nominal significant associations with increased ACE2 included inflammatory bowel disease, (ER+) breast and lung cancers, asthma, smoking and elevated ALT, among others. We also uncovered a number of plasma/serum proteins potentially linked to altered ACE2 expression, and the top enriched pathways included cytokine-cytokine-receptor interaction, VEGF signaling, JAK-STAT signaling etc. We also explored drugs that target some of the top-ranked proteins in the MR analysis. In conclusion, the current MR analysis reveals diseases/traits and blood proteins that may causally affect ACE2 expression, which in turn may influence susceptibility to the infection. The proteome-wide MR analysis may shed light on the molecular mechanisms underlying ACE2 expression, and may help guide drug repositioning in the future. Nevertheless, we stress that further studies are required to verify our findings due to various limitations and the exploratory nature of some analyses.</jats:p>",2020-03-08,"['Shitao Rao', 'Alexandria Lau', 'Hon-Cheong So']",,,,True
374a5295716649a80dca87097ad9ac902d344db6,medrxiv,Outcome reporting from protocols of clinical trials of Coronavirus Disease 2019 (COVID-19): a review,doi.org/10.1101/2020.03.04.20031401,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objectives: To examine heterogeneity of outcomes in protocols of clinical trials of Coronavirus Disease 2019 (COVID-19) and to identify outcomes for prioritization in developing a core outcome set (COS) in this field. Design: This study is a review. Data sources: Databases of ICMJE-accepted clinical trial registry platform were searched on February 14, 2020. Eligibility Criteria: Randomized controlled trials (RCTs) and non-RCTs of COVID-19 were considered.Conditions of patients include common type, severe type or critical type. Interventions include traditional Chinese medicine (TCM) and Western medicine. We excluded trials that for discharged patients, psychological intervention and complications of COVID-19. Data extraction and synthesis: The general information and outcomes, outcome measurement instruments and measurement times were extracted. The results were analysed by descriptive analysis.  Results: 19 registry platforms were searched. A total of 97 protocols were included from 160 protocols. For protocols of TCM clinical trials, 76 outcomes from 16 outcome domains were reported, and almost half (34/76, 44.74%) of outcomes were reported only once; the most frequently reported outcome was time of SARS-CoV-2 RNA turns to negative. 27 (27/76, 35.53%) outcomes were provided one or more outcome measurement instruments. 10 outcomes were provided one or more measurement time frame. For protocols of western medicine clinical trials, 126 outcomes from 17 outcome domains were reported; almost half (62/126, 49.21%) of outcomes were reported only once; the most frequently reported outcome was proportion of patients with negative SARS-CoV-2. 27 outcomes were provided one or more outcome measurement instruments. 40 (40/126, 31.75%) outcomes were provided one or more measurement time frame. Conclusion: Outcome reporting in protocols of clinical trials of COVID-19 is inconsistent. Thus, developing a core outcome set is necessary.  Keywords: Outcomes; clinical trials, COVID-19; review.</jats:p>",2020-03-08,"['Ruijin Qiu', 'Xuxu Wei', 'Mengzhu Zhao', 'Changming Zhong', 'Chen Zhao', 'Jiayuan Hu', 'Min Li', 'Ya Huang', 'Songjie Han', 'Tianmai He', 'Jing Chen', 'Hongcai Shang']",,,,True
9bbfd3d34ee18ea1b9f4669331a6cee9c5992893,medrxiv,Clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster,doi.org/10.1101/2020.03.05.20030502,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: In coronavirus disease 2019 (COVID-19), current case definitions presume mainly lower respiratory tract infection. However, cases seen outside the epicenter of the epidemic may differ in their overall clinical appearance due to more sensitive case finding. Methods: We studied viral load courses by RT-PCR in oro- and nasopharyngeal swabs, sputum, stool, blood, and urine in nine hospitalized cases. Infectious virus was detected by cell culture. Active replication was demonstrated by analysis of viral subgenomic replicative intermediates. Serology including neutralization testing was done to characterize immune response. Results: Seven cases had upper respiratory tract disease. Lower respiratory tract symptoms seen in two cases were limited. Clinical sensitivity of RT-PCR on swabs taken on days 1-5 of symptoms was 100%, with no differences comparing swab and sputum samples taken simultaneously. Average viral load was 6.76x10E5 copies per swab during the first 5 days. Live virus isolates were obtained from swabs during the first week of illness. Proof of active viral replication in upper respiratory tract tissues was obtained by detection of subgenomic viral RNA. Shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after about one week. Conclusions: The present study shows that COVID-19 can often present as a common cold-like illness. SARS-CoV-2 can actively replicate in the upper respiratory tract, and is shed for a prolonged time after symptoms end, including in stool. These findings suggest adjustments of current case definitions and re-evaluation of the prospects of outbreak containment.</jats:p>",2020-03-08,"['Roman Woelfel', 'Victor Max Corman', 'Wolfgang Guggemos', 'Michael Seilmaier', 'Sabine Zange', 'Marcel A Mueller', 'Daniela Niemeyer', 'Patrick Vollmar', 'Camilla Rothe', 'Michael Hoelscher', 'Tobias Bleicker', 'Sebastian Bruenink', 'Julia Schneider', 'Rosina Ehmann', 'Katrin Zwirglmaier', 'Christian Drosten', 'Clemens Wendtner']",,,,True
c8c052d27aaf8015316dcd2644fa5e0b3870cea1,medrxiv,Modeling the Comparative Impact of Individual Quarantine vs. Active Monitoring of Contacts for the Mitigation of COVID-19,doi.org/10.1101/2020.03.05.20031088,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Individual quarantine and active monitoring of contacts are core disease control strategies, particularly for emerging infectious diseases such as Coronavirus Disease 2019 (COVID-19). To estimate the comparative efficacy of these interventions to control COVID-19, we fit a stochastic branching model, comparing two sets of reported parameters for the dynamics of the disease. Our results suggest that individual quarantine may contain an outbreak of COVID-19 with a short serial interval (4.8 days) only in settings with high intervention performance where at least three-quarters of infected contacts are individually quarantined. However, in settings where this performance is unrealistically high and the outbreak of COVID-19 continues to grow, so too will the burden of the number of contacts traced for active monitoring or quarantine. In such circumstances where resources are prioritized for scalable interventions such as social distancing, we show active monitoring or individual quarantine of high-risk contacts can contribute synergistically to social distancing. To the extent that interventions based on contact tracing can be implemented, therefore, they can help mitigate the spread of COVID-19. Our model highlights the urgent need for more data on the serial interval and the extent of presymptomatic transmission in order to make data-driven policy decisions regarding the cost-benefit comparisons of individual quarantine vs. active monitoring of contacts.</jats:p>",2020-03-08,"['Corey M Peak', 'Rebecca Kahn', 'Yonatan H Grad', 'Lauren M Childs', 'Ruoran Li', 'Marc Lipsitch', 'Caroline O Buckee']",,,,True
a7ac40c0f2083c733cc714e563b21c2d606818c0,medrxiv,"Appealing for Efficient, Well Organized Clinical Trials on COVID-19",doi.org/10.1101/2020.03.05.20031476,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The rapid emergence of clinical trials on COVID-19 stimulated a wave of discussion in scientific community. We reviewed the characteristics of interventional trials from Chinese Clinical Trial Registration (ChiCTR) and ClinicalTrials.gov. A total of 171 COVID-19-related interventional trials were identified on Feb 22nd, 2020. These trials are classified into 4 categories based on treatment modalities, including chemical drugs, biological therapies, traditional Chinese medicine treatments and other therapies. Our analysis focused on the issues of stage, design, randomization, blinding, primary endpoints definition and sample size of these trials. We found some studies with potential defects including unreasonable design, inappropriate primary endpoint definition, insufficient sample size and ethical issue. Clinical trials on COVID-19 should be designed based on scientific rules, ethics and benefits for patients.</jats:p>",2020-03-07,"['Yang Zhao', 'Yongyue Wei', 'Sipeng Shen', 'Mingzhi Zhang', 'Feng Chen']",,,,True
f49a9b36227a498495c9788a4e5e4d6429b71eab,medrxiv,Clinical characterization and chest CT findings in laboratory-confirmed COVID-19: a systematic review and meta-analysis,doi.org/10.1101/2020.03.05.20031518,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Imagery techniques have been used as essential parts of diagnostic workup for patients suspected for 2019-nCoV infection, Multiple studies have reported the features of chest computed tomography (CT) scans among a number of 2019-nCoV patients.  Method: Study Identification was carried out in databases (PubMed, Embase and Cochrane Library) to identify published studies examining the diagnosis, the 2019 novel coronavirus (2019-nCoV). Heterogeneity among reported prevalence was assessed by computing p-values of Cochrane Q-test and I2-statics. The pooled prevalence of treatment failure was carried out with a fixed effects meta-analysis model, generating the pooled 95% confidence interval. A random-effect model was used to pool the results since this model could incorporate the heterogeneity of the studies and therefore proved a more generalized result.  Results:  According to the combined results of meta-analysis, the total 55% of corona patients were males. The mean age of the patients was 41.31 (34.14, 48.47). Two prevalent clinical symptoms between patients were fever, cough with prevalence of 85%, and 62%, respectively. Either Ground Glass Opacity GGO or consolidation was seen in 86% but 14% had NO GGO or consolidation.  The other rare CT symptoms were pericardial effusion, and pleural effusion with 4, 5, 7% prevalence, respectively. The most prevalent event was Either GGO or consolidation in 85% of patients.  Conclusion: The most CT-scan abnormality is Either Ground Glass Opacity GGO or consolidation however in few patients none of them might be observed, so trusting in just CT findings will lead to miss some patients.</jats:p>",2020-03-08,"['Golnaz Vaseghi', 'Marjan Mansourian', 'Raheleh Karimi', 'Kiyan Heshmat-Ghahdarijani', 'Sadegh Baradaran Mahdavi', 'Amirhossein Pezeshki', 'Behrooz Ataei', 'Alireza Zandifar', 'Omid Shafaat', 'Shaghayegh Haghjoo Javanmard']",,,,True
114ed64f52f503d9d2e2ba1fd1ee62b0a168cd84,medrxiv,Acute Myocardial Injury of Patients with Coronavirus Disease 2019,doi.org/10.1101/2020.03.05.20031591,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Since the outbreak of the Coronavirus Disease 2019 (COVID-19) in China, respiratory manifestations of the disease have been observed. However, as a fatal comorbidity, acute myocardial injury (AMI) in COVID-19 patients has not been previously investigated in detail. We investigated the clinical characteristics of COVID-19 patients with AMI and determined the risk factors for AMI in them. Methods: We analyzed data from 53 consecutive laboratory-confirmed and hospitalized COVID-19 patients (28 men, 25 women; age, 19-81 years). We collected information on epidemiological and demographic characteristics, clinical features, routine laboratory tests (including cardiac injury biomarkers), echocardiography, electrocardiography, imaging findings, management methods, and clinical outcomes.  Results: Cardiac complications were found in 42 of the 53 (79.25%) patients: tachycardia (n=15), electrocardiography abnormities (n=11), diastolic dysfunction (n=20), elevated myocardial enzymes (n=30), and AMI (n=6). All the six AMI patients were aged &gt;60 years; five of them had two or more underlying comorbidities (hypertension, diabetes, cardiovascular diseases, and chronic obstructive pulmonary disease). Novel coronavirus pneumonia (NCP) severity was higher in the AMI patients than in patients with non-definite AMI (p&lt;0.001). All the AMI patients required care in intensive care unit; of them, three died, two remain hospitalized. Multivariate analyses showed that C-reactive protein (CRP) levels, NCP severity, and underlying comorbidities were the risk factors for cardiac abnormalities in COVID-19 patients. Conclusions: Cardiac complications are common in COVID-19 patients. Elevated CRP levels, underlying comorbidities, and NCP severity are the main risk factors for cardiac complications in COVID-19 patients.</jats:p>",2020-03-08,"['Huayan Xu', 'Keke Hou', 'Hong Xu', 'Zhenlin Li', 'Huizhu Chen', 'Na Zhang', 'Rong Xu', 'Hang Fu', 'Ran Sun', 'Lingyi Wen', 'Linjun Xie', 'Hui Liu', 'Kun Zhang', 'Joseph B Selvanayagam', 'Chuan Fu', 'Shihua Zhao', 'Zhigang Yang', 'Ming Yang', 'Yingkun Guo']",,,,True
0b282573f5c63c943021c10ca39a1ed21acfb429,medrxiv,A data-driven assessment of early travel restrictions related to the spreading of the novel COVID-19 within mainland China,doi.org/10.1101/2020.03.05.20031740,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Two months after it was firstly reported, the novel coronavirus disease COVID-19 has already spread worldwide. However, the vast majority of reported infections have occurred in China. To assess the effect of early travel restrictions adopted by the health authorities in China, we have implemented an epidemic metapopulation model that is fed with mobility data corresponding to 2019 and 2020. This allows to compare two radically different scenarios, one with no travel restrictions and another in which mobility is reduced by a travel ban. Our findings indicate that i) travel restrictions are an effective measure in the short term, however, ii) they are ineffective when it comes to completely eliminate the disease. The latter is due to the impossibility of removing the risk of seeding the disease to other regions. Our study also highlights the importance of developing more realistic models of behavioral changes when a disease outbreak is unfolding.</jats:p>",2020-03-08,"['Alberto Aleta', 'Qitong Hu', 'Jiachen Ye', 'Peng Ji', 'Yamir Moreno']",,,,True
a34d2c1876ffedc4f95f3af13ac06039cd38a5b0,medrxiv,Estimating the infection and case fatality ratio for COVID-19 using age-adjusted data from the outbreak on the Diamond Princess cruise ship,doi.org/10.1101/2020.03.05.20031773,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Adjusting for delay from confirmation-to-death, we estimated case and infection fatality ratios (CFR, IFR) for COVID-19 on the Diamond Princess ship as 2.3% (0.75%-5.3%) and 1.2% (0.38-2.7%). Comparing deaths onboard with expected deaths based on naive CFR estimates using China data, we estimate IFR and CFR in China to be 0.5% (95% CI: 0.2-1.2%) and 1.1% (95% CI: 0.3-2.4%) respectively.</jats:p>",2020-03-08,,,,,True
af266fac8970a7960e96630a67d91bec5dda0335,medrxiv,Estimating the generation interval for COVID-19 based on symptom onset data,doi.org/10.1101/2020.03.05.20031815,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Estimating key infectious disease parameters from the COVID-19 outbreak is quintessential for modelling studies and guiding intervention strategies. Whereas different estimates for the incubation period distribution and the serial interval distribution have been reported, estimates of the generation interval for COVID-19 have not been provided. Methods: We used outbreak data from clusters in Singapore and Tianjin, China to estimate the generation interval from symptom onset data while acknowledging uncertainty about the incubation period distribution and the underlying transmission network. From those estimates we obtained the proportions pre-symptomatic transmission and reproduction numbers. Results: The mean generation interval was 5.20 (95%CI 3.78-6.78) days for Singapore and 3.95 (95%CI 3.01-4.91) days for Tianjin, China when relying on a previously reported incubation period with mean 5.2 and SD 2.8 days. The proportion of pre-symptomatic transmission was 48% (95%CI 32-67%) for Singapore and 62% (95%CI 50-76%) for Tianjin, China. Estimates of the reproduction number based on the generation interval distribution were slightly higher than those based on the serial interval distribution. Conclusions: Estimating generation and serial interval distributions from outbreak data requires careful investigation of the underlying transmission network. Detailed contact tracing information is essential for correctly estimating these quantities.</jats:p>",2020-03-08,"['Tapiwa Ganyani', 'Cecile Kremer', 'Dongxuan Chen', 'Andrea Torneri', 'Christel Faes', 'Jacco Wallinga', 'Niel Hens']",,,,True
a0ecc9b46addbc1faab491434b5331702f7883b8,medrxiv,A mathematical model for estimating the age-specific transmissibility of a novel coronavirus,doi.org/10.1101/2020.03.05.20031849,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: A novel coronavirus named as ""SARS-CoV-2"" has spread widely in many countries since December 2019, especially in China. This study aimed to quantify the age-specific transmissibility by using a mathematical model. Methods: An age-specific susceptible - exposed - symptomatic - asymptomatic - recovered - seafood market (SEIARW) model was developed based on two suspected transmission routes (from market to person and person to person). The susceptible people from Wuhan City were divided into different age groups. We used the subscript i and j to represent age group 1 to 4 (1: &lt;= 14 years; 2: 15-44 years; 3: 45-64 years; 4: &gt;= 65 years) and 1 to 5 (1: &lt;= 5 years; 2: 6-14 years; 3: 15-24 years; 4: 25-59 years; 4: &gt;= 60 years), respectively. Data of reported COVID-19 cases were collected from one published literature from 26 November to 22 December, 2019 in Wuhan City, China. The age-specific transmissibility of the virus was estimated accordingly secondary attack rate (SAR).  Results: The age-specific SEIARW model fitted with the reported data well by dividing the population into four age groups (χ2 = 4.99 × 10-6, P &gt; 0.999), and five age groups (χ2 = 4.85 × 10-6, P &gt; 0.999). Based on the four-age-group SEIARW model, the highest transmissibility occurred from age group 2 to 3 (SAR23 = 17.56 per 10 million persons), followed by from age group 3 to 2 (SAR32 = 10.17 per 10 million persons). The lowest transmissibility occurred from age group 1 to 2 (SAR12 = 0.002 per 10 million persons). Based on the five-age-group SEIARW model, the highest transmissibility occurred from age group 4 to 5 (SAR45 = 12.40 per 10 million persons), followed by from age group 5 to 4 (SAR54 = 6.61 per 10 million persons). The lowest transmissibility occurred from age group 3 to 4 (SAR34 = 0.0002 per 10 million persons). Conclusions: SARS-CoV-2 has high transmissibility among adults and elder people but low transmissibility among children and young people.</jats:p>",2020-03-08,"['Zeyu Zhao', 'Yuan-Zhao Zhu', 'Jing-Wen Xu', 'Qing-Qing Hu', 'Zhao Lei', 'Jia Rui', 'Xingchun Liu', 'Yao Wang', 'Li Luo', 'Shan-Shan Yu', 'Jia Li', 'Ruo-Yun Liu', 'Fang Xie', 'Ying-Ying Su', 'Yi-Chen Chiang', 'Yanhua Su', 'Benhua Zhao', 'Tianmu Chen']",,,,True
b4edd81e0d2770b0d6e0e3c93c7fffc43e3caa80,medrxiv,Role of temperature and humidity in the modulation of the doubling time of COVID-19 cases,doi.org/10.1101/2020.03.05.20031872,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>COVID-19 is having a great impact on public health, mortality and economy worldwide, in spite of the efforts to prevent its epidemy. The SARS-CoV-2 genome is different from that of MERS-CoV and SARS-CoV, although also expected to spread differently according to meteorological conditions. Our main goal is to investigate the role of some meteorological variables on the expansion of this outbreak. In this study, an exponential model relating the number of accumulated confirmed cases and time was considered. The rate of COVID-19 spread, using as criterion the doubling time of the number of confirmed cases, was used as dependent variable in a linear model that took four independent meteorological variables: temperature, humidity, precipitation and wind speed. Only China cases were considered, to control both cultural aspects and containment policies. Confirmed cases and the 4 meteorological variables were gathered between January 23 and March 1 (39 days) for the 31 provinces of Mainland China. Several periods of time were sampled for each province, obtaining more than one value for the rate of disease progression. Two different periods of time were tested, of 12 and 15 days, along with 3 and 5 different starting points in time, randomly chosen. The median value for each meteorological variable was computed, using the same time period; models with adjusted R square above 0.75 were selected. The rate of progression and doubling time were computed and used to fit a linear regression model. Models were evaluated using alpha=0.05. Results indicate that the doubling time correlates positively with temperature and inversely with humidity, suggesting that a decrease in the rate of progression of COVID-19 with the arrival of spring and summer in the north hemisphere. A 20oC increase is expected to delay the doubling time in 1.8 days. Those variables explain 18% of the variation in disease doubling time; the remaining 82% may be related to containment measures, general health policies, population density, transportation or cultural aspects.</jats:p>",2020-03-08,"['Barbara Oliveiros', 'Liliana Caramelo', 'Nuno C Ferreira', 'Francisco Caramelo']",,,,True
a42ff48d50aa3a0ebfe840d46ed2204c49955442,medrxiv,Emotional responses and coping strategies of nurses and nursing college students during COVID-19 outbreak,doi.org/10.1101/2020.03.05.20031898,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: Affected by a Corona Virus Disease 2019 (COVID-19) outbreak, Since December 2019, there have been more than 76,000 cases of COVID-19 in China, causing more than 3,000 medical staff infections. Due to COVID-19 spreads quickly, is highly contagious, and can be fatal in severe cases, and there are no specific medicines, it poses a huge threat to the life and health of nurses and has a large impact on their emotional responses and coping strategies. Methods: This study conducted an online questionnaire survey from February 1 to 9, 2020 to investigate the current state of emotional responses and coping strategies of nurses and college nursing students in Anhui Province. This study used a modified Brief COPE (Carver, 1997) and a emotional responses scale. Results: The results found that women showed more severe anxiety and fear than men. Participants from cities showed more anxiety and fear than participants from rural, but rural participants showed more sadness than urban participants. The closer COVID-19 is to the participants, the stronger the anxiety and anger. Compared with Nursing college students, nurses have stronger emotional responses and are more willing to use Problem-focused coping. People may have a cycle of ""the more fear, the more problem-focused coping"". And people may ""The more angry, the more emotion-focused coping"", ""the more problem-focused coping, the more anxious, the more angry, the more sadness"".    Conclusion: COVID-19 is a pressure source with great influence, both for individuals and for the social public groups. Different individuals and groups may experience different levels of psychological crisis, and those nurses at the core of the incident are affected. Hospitals should focus on providing psychological support to nurses and providing timely psychological assistance and training in coping strategies. Improving nurses' ability to regulate emotions and effective coping strategies, providing a strong guarantee for resolutely winning the battle against epidemic prevention and control.</jats:p>",2020-03-08,"['Long Huang', 'Fu ming xu', 'Hai rong Liu']",,,,True
5129bb31949c66ebd544658c531004046d4102da,medrxiv,COVID-19 early warning score: a multi-parameter screening tool to identify highly suspected patients,doi.org/10.1101/2020.03.05.20031906,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>BACKGROUND Corona Virus Disease 2019 (COVID-19) is spreading worldwide. Effective screening for patients is important to limit the epidemic. However, some defects make the currently applied diagnosis methods are still not very ideal for early warning of patients. We aimed to develop a diagnostic model that allows for the quick screening of highly suspected patients using easy-to-get variables. METHODS A total of 1,311 patients receiving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleicacid detection were included, whom with a positive result were classified into COVID-19 group. Multivariate logistic regression analyses were performed to construct the diagnostic model. Receiver operating characteristic (ROC) curve analysis were used for model validation. RESULTS After analysis, signs of pneumonia on CT, history of close contact, fever, neutrophil-to-lymphocyte ratio (NLR), Tmax and sex were included in the diagnostic model. Age and meaningful respiratory symptoms were enrolled into COVID-19 early warning score (COVID-19 EWS). The areas under the ROC curve (AUROC) indicated that both of the diagnostic model (training dataset 0.956 [95%CI 0.935-0.977, P &lt; 0.001]; validation dataset 0.960 [95%CI 0.919-1.0, P &lt; 0.001] ) and COVID-19 EWS (training dataset 0.956 [95%CI 0.934-0.978, P &lt; 0.001] ; validate dataset 0.966 [95%CI 0.929-1, P &lt; 0.001]) had good discrimination capacity. In addition, we also obtained the cut-off values of disease severity predictors, such as CT score, CD8+ T cell count, CD4+ T cell count, and so on. CONCLUSIONS The new developed COVID-19 EWS was a considerable tool for early and relatively accurately warning of SARS-CoV-2 infected patients.</jats:p>",2020-03-08,"['Cong-Ying Song', 'Jia Xu', 'Jian-Qin He', 'Yuan-Qiang Lu']",,,,True
e05c39ce913edc81f93c9247f9714d6cddd30073,medrxiv,Sensitive one-step isothermal detection of pathogen-derived RNAs,doi.org/10.1101/2020.03.05.20031971,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The recent outbreaks of Ebola, Zika, MERS, and SARS-CoV-2 (2019-nCoV) require fast, simple, and sensitive onsite nucleic acid diagnostics that can be developed rapidly to prevent the spread of diseases. We have developed a SENsitive Splint-based one-step isothermal RNA detection (SENSR) method for rapid and straightforward onsite detection of pathogen RNAs with high sensitivity and specificity. SENSR consists of two simple enzymatic reactions: a ligation reaction by SplintR ligase and subsequent transcription by T7 RNA polymerase. The resulting transcript forms an RNA aptamer that induces fluorescence. Here, we demonstrate that SENSR is an effective and highly sensitive method for the detection of the current epidemic pathogen, <jats:italic>severe acute respiratory syndrome-related coronavirus 2</jats:italic> (SARS-CoV-2). We also show that the platform can be extended to the detection of five other pathogens. Overall, SENSR is a molecular diagnostic method that can be developed rapidly for onsite uses requiring high sensitivity, specificity, and short assaying times.</jats:p>",2020-03-09,"['Chang Ha Woo', 'Sungho Jang', 'Giyoung Shin', 'Gyoo Yeol Jung', 'Jeong Wook Lee']",,,,True
083dd400b7854ffa908a21641197855aee981ea5,medrxiv,The prevalence and influencing factors for anxiety in medical workers fighting COVID-19 in China: A cross-sectional survey,doi.org/10.1101/2020.03.05.20032003,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Abstract: Background: The COVID-19 outbreak caused by the SARS-Cov-2 virus has been sustained in China since December 2019, and could become a pandemic if we do not contain it. The mental health of frontline medical staff is a concern. In this study, we aimed to identify the influencing factors on medical worker anxiety in China during the COVID-19 outbreak.  Methods: We conducted a cross-sectional study to estimate the prevalence of anxiety among medical staff from 10th February 2020 to 20th February 2020 in China using the Zung Self-rating Anxiety Scale (SAS) to assess anxiety, using the criteria of normal (≤49), mild (50-59), moderate (60-70) and severe anxiety (≥70). We used multivariable linear regression to determine the factors (e.g., having direct contact treating infected patients, being a medical staff worker from Hubei province, being a suspect case) for anxiety. We also used adjusted models to confirm independent factors for anxiety after adjusting for gender, age, education and marital status.  Results: Of 512 medical staff from China, 164 healthcare workers (32.03%) had had direct contact by treating infected patients. The prevalence of anxiety was 12.5%, with 53 workers suffering from mild (10.35%), seven workers from moderate (1.36%) and four workers from severe anxiety (0.78%). After adjusting for sociodemographic characteristics (gender, age, education and marital status), medical staff who had had direct contact treating infected patients saw higher anxiety scores than those who had not had direct contact (βvalue=2.33, CI: 0.65 -4.00; p=0.0068). Similar things were observed in medical staff from Hubei province, compared with those from other parts of China (βvalue=3.67, CI: 1.44 -5.89; p=0.0013). The most important variable was suspect cases with high anxiety scores, compared to non-suspect cases (βvalue=4.44, CI: 1.55 -7.33; p=0.0028). Conclusion: Our results highlight that government authorities should make early detection of the high risk of anxiety among medical staff a priority, and implement appropriate psychological intervention programs, to prevent medical staff from developing psychological disorders that could potentially exert an adverse effect on combating the COVID-19 epidemic.</jats:p>",2020-03-08,"['Chenyun Liu', 'Yun-zhi Yang', 'Xiao Ming Zhang', 'Xinying Xu', 'Qing-Li Dou', 'Wen-Wu Zhang']",,,,False
93d8f1552a81587e2f88e38580cbe4753b9934f1,medrxiv,Amplicon based MinION sequencing of SARS-CoV-2 and metagenomic characterisation of nasopharyngeal swabs from patients with COVID-19,doi.org/10.1101/2020.03.05.20032011,,,See https://www.medrxiv.org/submit-a-manuscript,<jats:p>COVID-19 is a complex disease phenotype where the underlying microbiome could influence morbidity and mortality. Amplicon and metagenomic MinION based sequencing was used to rapidly (within 8 hours) identify SARS-CoV-2 and assess the microbiome in nasopharyngeal swabs obtained from patients with COVID-19 by the ISARIC 4C consortium.</jats:p>,2020-03-08,"['Shona C Moore', 'Rebekah Penrice-Randal', 'Muhannad Alruwaili', 'Xiaofeng Dong', 'Steven T Pullan', 'Daniel Carter', 'Kevin Bewley', 'Qin Zhao', 'Yani Sun', 'Catherine Hartley', 'En-min Zhou', 'Tom Solomon', 'Michael B. J. Beadsworth', 'James Cruise', 'Debby Bogaert', 'Derrick W T Crook', 'David A Matthews', 'Andrew D. Davidson', 'Zana Mahmood', 'Waleed Aljabr', 'Julian Druce', 'Richard T Vipond', 'Lisa Ng', 'Laurent Renia', 'Peter Openshaw', 'J Kenneth Baillie', 'Miles W Carroll', 'Calum Semple', 'Lance Turtle', 'Julian Alexander Hiscox']",,,,True
dd2cd004a197872cfce1c31a9685d6972f838efa,medrxiv,The Impact of Host-Based Early Warning on Disease Outbreaks,doi.org/10.1101/2020.03.06.20029793,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective: The detection of communicable pathogens responsible for major outbreaks relies on health care professionals recognition of symptoms manifesting in infectious individuals. Early warning of such communicable diseases before the onset of symptoms could improve both patient care and public health responses. However, the potential impact of such a host-based early warning system on containing the spread of an outbreak and in steering public health response is unknown. Methods: We extend the deterministic SEIR (Susceptible, Exposed, Infectious, Recovered) model to simulate disease outbreak scenarios and to quantify the potential impact of a host-based early warning capability to mitigate pathogen transmission during an outbreak. In particular, we compare and contrast the performance of five different policies: Self-monitoring and reporting (baseline SEIR model), Quarantining the entire population, Quarantine-on-alert (with high sensitivity early warning), Quarantine-on-alert (with high specificity early warning), and Quarantine-on-alert (ideal early warning). We further evaluate these five policy options against four different outbreak scenarios with high or low disease transmission and high or low initial population exposures. Results: For all scenarios, a quarantine-on-alert policy coupled with the near-ideal early warning capability reduces quarantine needs with only a small increase in the number of additional infections. The cost of a highly specific early detection system (i.e., a reduction in false alarms and thus quarantine costs) is an increase in additional infections relative to the near-ideal system. Conversely, a highly sensitive early detection system increases the percentage of the population in quarantine compared to both the ideal and high-specificity early detection system while also reducing the number of additional infections to nearly the numbers seen by quarantining the entire population a priori.  Conclusions: Our simulations demonstrate the utility of host-based early warning systems in controlling an outbreak under various outbreak conditions. Our tools also provide a simulation capability for evaluating public health policies enabling quantitative evaluation of their impacts prior to implementation.</jats:p>",2020-03-08,"['Mark Hernandez', 'Lauren E Milechin', 'Shakti K Davis', 'Rich DeLaura', 'Kajal T Claypool', 'Albert Swiston']",,,,True
e53f5a6c4cbac340f0d97a4ba3289c30b7222dd5,medrxiv,The Evaluation of Sleep Disturbances for Chinese Frontline Medical Workers Under the Outbreak of COVID-19,doi.org/10.1101/2020.03.06.20031278,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objective To evaluate sleep disturbances of Chinese frontline medical workers (fMW) under the outbreak of coronavirus disease 2019, and make a comparison with non-fMW. Methods The medical workers from multiple hospitals in Hubei Province, China, were volunteered to participate in this cross-sectional study. An online questionnaire, including Pittsburgh Sleep Quality Index (PSQI), Athens Insomnia Scale (AIS) and Visual Analogue Scale (VAS), was used to evaluate sleep disturbances and mental status of fMW. Sleep disturbances were defined as PSQI&gt;7 points or/and AIS&gt;6 points. We compared the scores of PSQI, AIS, anxiety and depression VAS and prevalence of sleep disturbances between fMW and non-fMW. Subgroup analysis for different gender in fMW was conducted.  Results A total of 1306 subjects (including 801 fMW and 505 non-fMW) were enrolled. Compared to non-fMW, fMW had significantly higher scores of PSQI (9.3 vs 7.5, P＜0.001), AIS (6.9 vs 5.3, P＜0.001), anxiety (4.9 vs 4.3, P＜0.001) and depression (4.1 vs 3.6, P=0.001), and higher prevalence of sleep disturbances with PSQI &gt; 7 points (67.2% vs 47.7%, P＜0.001) and AIS &gt; 6 points (51.7% vs 35.6%, P＜0.001). In subgroup analysis, compared to male fMW, female fMW had significantly higher scores of PSQI (9.4 vs 8.6, P=0.022) and higher prevalence of sleep disturbances with PSQI &gt; 7 points (70.3% vs 54.6%, P&lt;0.001). Conclusion fMW had higher prevalence of sleep disturbances and worse sleep quality than non-fMW. Female fMW were more vulnerable to having sleep disturbances than male fMW.</jats:p>",2020-03-08,"['Jing Qi', 'Jing Xu', 'Bozhi Li', 'Jinsha Huang', 'Yuan Yang', 'Zhentao Zhang', 'Dongai Yao', 'Qunhui Liu', 'Min Jia', 'Daokai Gong', 'Xiaohong Ni', 'Qimei Zhang', 'Furong Shang', 'Nian Xiong', 'Chunli Zhu', 'Tao Wang', 'Xi Zhang']",,,,True
fd847a97e6fce134345b25ae9240c4ebb680cca5,medrxiv,Clinical Characteristics on 25 Discharged Patients with COVID-19 Virus Returning,doi.org/10.1101/2020.03.06.20031377,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Here we report the clinical features of 25 discharged patients with COVID-19 recovery. Our analysis indicated that there was a significant inverse correlation existed between serum D-Dimer level and the duration of antiviral treatment, while lymphocyte concentration significantly positively correlated with the duration of virus reversal.</jats:p>",2020-03-10,"['Jing Yuan', 'Shanglong Kou', 'Yanhua Liang', 'Jianfeng Zeng', 'Yanchao Pan', 'Lei Liu']",,,,True
610549c879c62efc42f2ad32f63c65b25d8931c7,medrxiv,A preliminary study on serological assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 238 admitted hospital patients,doi.org/10.1101/2020.03.06.20031856,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background The outbreak of the recently emerged novel corona virus disease 2019 (COVID-19) poses a challenge for public health laboratories. We aimed to evaluate the diagnostic value of serological assay for SARS-CoV-2.  Methods A newly-developed ELISA assay for IgM and IgG antibodies against N protein of SARS-CoV-2 were used to screen the serums of 238 admitted hospital patients with confirmed or suspected SARS-CoV-2 infection from February 6 to February 14, 2020. SARS-CoV-2 RNA was detected by real time RT-PCR on pharyngeal swab specimens. Findings Of the 238 patients, 194 (81.5%) were detected to be antibody (IgM and/or IgG) positive, which was significantly higher than the positive rate of viral RNA (64.3%). There was no difference in the positive rate of antibody between the confirmed patients (83.0%, 127/153) and the suspected patients (78.8%, 67/85) whose nucleic acid tests were negative. After the patients were defined to the different stages of disease based on the day when the test samples were collected, the analysis results showed that the antibody positive rates were very low in the first five days after initial onset of symptoms, and then rapidly increased as the disease progressed. After 10 days, the antibody positive rates jumped to above 80% from less than 50%. On the contrary, the positive rates of viral RNA kept above 60% in the first 11 days after initial onset of symptoms, and then rapidly decreased. In addition, half of the suspected patients with symptoms for 6-10 days were detected to be antibody positive. Interpretation The suspected patients were most likely infected by SARS-CoV-2. Before the 11th day after initial onset of symptoms, nucleic acid test is important for confirmation of viral infection. The combination of serological assay can greatly improve the diagnostic efficacy. After that, the diagnosis for viral infection should be majorly dependent on serological assay. Keywords. SARS-CoV-2; diagnosis; serological assay; nucleic acid test</jats:p>",2020-03-08,"['Lei Liu', 'Wanbing Liu', 'Shengdian Wang', 'Shangen Zheng']",,,,True
088d5c4a4f212be9590b6ce3d70a8e01847e76cf,medrxiv,"Estimating the scale of COVID-19 Epidemic in the United States: Simulations Based on Air Traffic directly from Wuhan, China",doi.org/10.1101/2020.03.06.20031880,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Introduction: Coronavirus Disease 2019 (COVID-19) infection has been characterized by rapid spread and unusually large case clusters. It is important to have an estimate of the current state of COVID-19 epidemic in the U.S. to develop informed public health strategies.  Methods:  We estimated the potential scale of the COVID-19 epidemic (as of 03/01/2020) in the U.S. from cases imported directly from Wuhan area. We used simulations based on transmission dynamics parameters estimated from previous studies and air traffic data from Wuhan to the U.S and deliberately built our model based on conservative assumptions. Detection and quarantine of individual COVID-19 cases in the U.S before 03/01/2020 were also taken into account. We. A SEIR model was used to simulate the growth of the number of infected individuals in Wuhan area and in the U.S.  Results: With the most likely model, we estimated that there would be 9,484 infected cases (90%CI 2,054-24,241) as of 03/01/2020 if no intervention procedure had been taken to reduce the transmissibility in unidentified cases. Assuming current preventive procedures have reduced 25% of the transmissibility in unidentified cases, the number of infected cases would be 1,043 (90%CI 107-2,474). Conclusion: Our research indicates that, as of 03/01/2020., it is likely that there are already thousands of individuals in the US infected with SARS-CoV-2. Our model is dynamic and is available to the research community to further evaluate as the  situation becomes clearer.</jats:p>",2020-03-08,"['Dalin Li', 'Jun Lv', 'Gregory Botwin', 'Jonathan Braun', 'Weihua Cao', 'Liming Li', 'Dermot P.B. McGovern']",,,,False
fd96fc1859201e13e35526c188e022fa6e335327,medrxiv,Transmission of corona virus disease 2019 during the incubation period may lead to a quarantine loophole,doi.org/10.1101/2020.03.06.20031955,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: The ongoing outbreak of novel corona virus disease 2019 (COVID-19) in Wuhan, China, is arousing international concern. This study evaluated whether and when the infected but asymptomatic cases during the incubation period could infect others.  Methods: We collected data on demographic characteristics, exposure history, and symptom onset day of the confirmed cases, which had been announced by the Chinese local authorities. We evaluated the potential of transmission during the incubation period in 50 infection clusters, including 124 cases. All the secondary cases had a history of contact with their first-generation cases prior to symptom onset.  Results: The estimated mean incubation period for COVID-19 was 4.9 days (95% confidence interval [CI], 4.4 to 5.4) days, ranging from 0.8 to 11.1 days (2.5th to 97.5th percentile). The observed mean and standard deviation (SD) of serial interval was 4.1±3.3 days, with the 2.5th and 97.5th percentiles at -1 and 13 days. The infectious curve showed that in 73.0% of the secondary cases, their date of getting infected was before symptom onset of the first-generation cases, particularly in the last three days of the incubation period.  Conclusions: The results indicated the transmission of COVID-9 occurs among close contacts during the incubation period, which may lead to a quarantine loophole. Strong and effective countermeasures should be implemented to prevent or mitigate asymptomatic transmission during the incubation period in populations at high risk.</jats:p>",2020-03-08,"['Wei Xia', 'Jiaqiang Liao', 'Chunhui Li', 'Yuanyuan Li', 'Xi Qian', 'Xiaojie Sun', 'Hongbo Xu', 'Gaga Mahai', 'Xin Zhao', 'Lisha Shi', 'Juan Liu', 'Ling Yu', 'Meng Wang', 'Qianqian Wang', 'Asmagvl Namat', 'Ying Li', 'Jingyu Qu', 'Qi Liu', 'Xiaofang Lin', 'Shuting Cao', 'Shu Huan', 'Jiying Xiao', 'Fengyu Ruan', 'Hanjin Wang', 'Qing Xu', 'Xingjuan Ding', 'Xingjie Fang', 'Feng Qiu', 'Jiaolong Ma', 'Yu Zhang', 'Aizhen Wang', 'Yuling Xing', 'Shunqing Xu']",,,,True
26e75d3c815aae7fd9b094c3e5c74d3f7132ca13,medrxiv,CORONAVIRUS IN PREGNANCY AND DELIVERY: RAPID REVIEW AND EXPERT CONSENSUS,doi.org/10.1101/2020.03.06.20032144,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>BACKGROUND Person to person spread of COIVD-19 in the UK has now been confirmed. There are limited case series reporting the impact on women affected by coronaviruses (CoV) during pregnancy. In women affected by SARS and MERS, the case fatality rate appeared higher in women affected in pregnancy compared with non-pregnant women. We conducted a rapid, review to guide management of women affected by COVID -19 during pregnancy and developed interim practice guidance with the RCOG and RCPCH to inform maternity and neonatal service planning METHODS Searches were conducted in PubMed and MedRxiv to identify primary case reports, case series, observational studies or randomised-controlled trial describing women affected by coronavirus in pregnancy and on neonates. Data was extracted from relevant papers and the review was drafted with representatives of the RCPCH and RCOG who also provided expert consensus on areas where data were lacking  RESULTS From 9964 results on PubMed and 600 on MedRxiv, 18 relevant studies (case reports and case series) were identified. There was inconsistent reporting of maternal, perinatal and neonatal outcomes across case reports and series concerning COVID-19, SARS, MERS and other coronaviruses. From reports of 19 women to date affected by COVID-19 in pregnancy, delivering 20 babies, 3 (16%) were asymptomatic, 1 (5%) was admitted to ICU and no maternal deaths have been reported. Deliveries were 17 by caesarean section, 2 by vaginal delivery, 8 (42%) delivered pre-term. There was one neonatal death, in 15 babies who were tested there was no evidence of vertical transmission. CONCLUSIONS Morbidity and mortality from COVID-19 appears less marked than for SARS and MERS, acknowledging the limited number of cases reported to date. Pre-term delivery affected 42% of women hospitalised with COVID-19, which may put considerable pressure on neonatal services if the UK reasonable worse-case scenario of 80% of the population affected is realised. There has been no evidence of vertical transmission to date.  The RCOG and RCPCH have provided interim guidance to help maternity and neonatal services plan their response to COVID-19.</jats:p>",2020-03-08,"['Edward Mullins', 'David Evans', 'Russell Viner', ""Patrick O'Brien"", 'Eddie Morris']",,,,True
bd08e2cbbc561e52823aedd0180f844e0c6cd2a6,medrxiv,Evaluating the secondary transmission pattern and epidemic prediction of the COVID-19 in metropolitan areas of China,doi.org/10.1101/2020.03.06.20032177,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Understanding the transmission dynamics of COVID-19 is crucial for evaluating the spread pattern of it, especially in metropolitan areas of China which may cause secondary outbreaks outside Wuhan, the center of the new coronavirus disease outbreak. We used reported data from Jan 24, 2020, to Feb 23, 2020, fitted the model of infection, and on the number of cases reported to estimate likely number of infections in four high risk metropolitan areas, as well as facilitate understanding the COVID-19's spread pattern. A group of SERI model statistical parameters were estimated using Markov Chain Monte Carlo (MCMC) methods, and our modeling integrated the effect of the official quarantine regulation and travel restriction of China. As a result, we estimated that the basic reproductive number R0 ​is 3.11 in Beijing, 2.78 in Shanghai, 2.02 in Guangzhou, and 1.75 in Shenzhen. In addition, we inferred the prediction results and compared the results of different level of parameters, For example, In Beijing, the predicated peak number of cases is around 466 at the peak time Feb 29, 2020; however, when the city conducts different levels (strict, mild, or weak) of travel restrictions or regulation measures, the estimation results show that transmission dynamics will change and the peek number of cases shows the changing proportion is between 56%~159%. We concluded that public health interventions would reduce the risks of COVID-19 spreading and more rigorous control and prevention measures will effectively contain its further spread, but risk increases when businesses and social activities returning back before the ending date. Besides, the experiences gained and lessons learned from China are potential to provide evidences supporting for other metropolitan areas and big cities with emerging cases outside China.</jats:p>",2020-03-08,"['Na Hong', 'Jie He', 'Yingying Ma', 'Huizhen Jiang', 'Lin Han', 'Longxiang Su', 'Weiguo Zhu', 'Yun Long']",,,,False
ea17aad7692bb5040f3b2ba1d01b8249e4969469,medrxiv,Rapid Detection of 2019 Novel Coronavirus SARS-CoV-2 Using a CRISPR-based DETECTR Lateral Flow Assay,doi.org/10.1101/2020.03.06.20032334,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>An outbreak of novel betacoronavirus, SARS-CoV-2 (formerly named 2019-nCoV), began in Wuhan, China in December 2019 and the COVID-19 disease associated with infection has since spread rapidly to multiple countries. Here we report the development of SARS-CoV-2 DETECTR, a rapid (~30 min), low-cost, and accurate CRISPR-Cas12 based lateral flow assay for detection of SARS-CoV-2. We validated this method using contrived reference samples and clinical samples from infected US patients and demonstrated comparable performance to the US CDC SARS-CoV-2 real-time RT-PCR assay.</jats:p>",2020-03-10,"['James P Broughton', 'Xianding Deng', 'Guixia Yu', 'Clare L Fasching', 'Jasmeet Singh', 'Jessica Streithorst', 'Andrea Granados', 'Alicia Sotomayor-Gonzalez', 'Kelsey Zorn', 'Allan Gopez', 'Elaine Hsu', 'Wei Gu', 'Steven Miller', 'Chao-Yang Pan', 'Hugo Guevara', 'Debra Wadford', 'Janice Chen', 'Charles Y Chiu']",,,,True
6d3b3f4ab80a61c45f82c61c6c756cfc6ddf4bf2,medrxiv,Estimation of incubation period distribution of COVID-19 using disease onset forward time: a novel cross-sectional and forward follow-up study,doi.org/10.1101/2020.03.06.20032417,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background:  The current outbreak of coronavirus disease 2019 (COVID-19) has quickly spread across countries and become a global crisis. However, one of the most important clinical characteristics in epidemiology, the distribution of the incubation period, remains unclear. Different estimates of the incubation period of COVID-19 were reported in recent published studies, but all have their own limitations. In this study, we propose a novel low-cost and accurate method to estimate the incubation distribution.   Methods: We have conducted a cross-sectional and forward follow-up study by identifying those asymptomatic individuals at their time of departure from Wuhan and then following them until their symptoms developed. The renewal process is hence adopted by considering the incubation period as a renewal and the duration between departure and symptom onset as a forward recurrence time. Under mild assumptions, the observations of selected forward times can be used to consistently estimate the parameters in the distribution of the incubation period. Such a method enhances the accuracy of estimation by reducing recall bias and utilizing the abundant and readily available forward time data.   Findings:  The estimated distribution of forward time fits the observations in the collected data well. The estimated median of incubation period is 8.13 days (95% confidence interval [CI]: 7.37-8.91), the mean is 8.62 days (95% CI: 8.02-9.28), the 90th percentile is 14.65 days (95% CI: 14.00-15.26), and the 99th percentile is 20.59 days (95% CI: 19.47, 21.62). Compared with results in other studies, the incubation period estimated in this study is longer.  Interpretation: Based on the estimated incubation distribution in this study, about 10% of patients with COVID-19 would not develop symptoms until 14 days after infection. Further study of the incubation distribution is warranted to directly estimate the proportion with long incubation periods.</jats:p>",2020-03-10,"['Qin Jing', 'Chong You', 'Qiushi Lin', 'Taojun Hu', 'Shicheng Yu', 'Xiao-Hua Zhou']",,,,True
3ba79e5d013c7c3cccd1449ccd16b93c61a4c576,medrxiv,"Prevalence and Risk Factors of Acute Posttraumatic Stress Symptoms during the COVID-19 Outbreak in Wuhan, China",doi.org/10.1101/2020.03.06.20032425,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background A novel coronavirus (SARA-CoV-2) emerged in Wuhan, China, in December 2019. Within a few weeks, the disease caused by SARA-CoV-2, which is named COVID-19, has escalated into an unprecedented ongoing outbreak with frightening speed, becoming a global health emergency. This study aimed to exam the prevalence and risk factors of acute posttraumatic stress symptoms (PTSS) in Chinese people shortly after the massive outbreak of COVID-19.  Method An online anonymous questionnaire survey was conducted in mainland China between 30 January and 3 February, 2020. The survey consisted of two self-administered questionnaires: one was designed to require personal information (gender, age, education background), current location, recent exposure history of Wuhan, the classification of population, and subjective sleep quality; the other was the PTSD Checklist for DSM-5 (PCL-5), which was to assess PTSS referring to the outbreak.  Results A total of 2091 Chinese participated in the current study. The prevalence of PTSS among the public in mainland China 1 month after the COVID-19 outbreak was 4.6%. Multiple linear regression analysis revealed that gender (p &lt; 0.001), exposure history of Wuhan (p = 0.047), classification of population (p &lt; 0.001), and subjective sleep quality (p &lt; 0.001) could be regarded as predictor factors for PTSS.  Conclusions The results showed that some Chinese showed acute PTSS during the COVID-19 outbreak. Therefore, comprehensive psychological intervention needs further implementation. Furthermore, females, people who having recent exposure history of Wuhan, those at high risk of infection or with poor sleep quality deserve special attention.</jats:p>",2020-03-10,"['Luna Sun', 'Zhuoer Sun', 'Lili Wu', 'Zhenwen Zhu', 'Fan Zhang', 'Zhilei Shang', 'Yanpu Jia', 'Jingwen Gu', 'Yaoguang Zhou', 'Yan Wang', 'Nianqi Liu', 'Weizhi Liu']",,,,False
c1a08ce8f2c5d5311b19822c3df5aa9d25c4d93c,medrxiv,"The epidemiological characteristics of 2019 novel coronavirus diseases (COVID-19) in Jingmen,Hubei,China",doi.org/10.1101/2020.03.07.20031393,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Summary Background: Some articles have reported the epidemiological and clinical characteristics of coronavirus disease (COVID-19) in Wuhan, but other cities have rarely been reported. This study explored the epidemiology of COVID-19 in Jingmen. Methods: All confirmed cases of COVID-19 in the First People′s Hospital of Jingmen are included from January 12 to February 14,2020. Cases were analyzed for epidemiological data and were confirmed by real-time PCR.  Findings: Of the 213 cases (108 men and 105 women) , 88 (41%) had exposure to Wuhan. The median age was 48 years ( range,2-88 years;IQR,35-58.5). Thirty-three severe patients with a median age of 66 years(range,33-82 years,IQR, 57-76) were treated in intensive care units; out of these patients, 66.7 %(22)  were men and 19 (57.5%) had chronic diseases, including hypertension, diabetes, heart failure, stroke, and renal insufficiency. Under the controlled measures, the number of new patients gradually decreased and nearly disappeared after 20 days. Interpretation: All people are susceptible to the COVID-19, but older males and those with comorbid conditions are more likely to have severe symptoms. Even though COVID-19 is highly contagious, control measures have proven to be very effective.</jats:p>",2020-03-10,"['Qijun Gao', 'yingfu hu', 'zhiguo dai', 'Jing wu', 'Feng Xiao', 'Jing wang']",,,,True
c6012a6141f5ad05ac983aa9f1a7c57938363b16,medrxiv,Prognostic value of NT-proBNP in patients with severe COVID-19,doi.org/10.1101/2020.03.07.20031575,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury was dominate in the process. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of COVID-19 patients was unknown. The study initially enrolled 102 patients with severe COVID-19 pneumonia from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. Results found that patients with higher NT-proBNP (above 88.64 pg/mL) level had more risks of in-hospital death. After adjusting for potential cofounders in separate modes, NT-proBNP presented as an independent risk factor of in-hospital death in patients with severe COVID-19.</jats:p>",2020-03-10,"['Lei Gao', 'Dan Jiang', 'Xuesong Wen', 'Xiaocheng Cheng', 'Min Sun', 'Bin He', 'Lin-na You', 'Peng Lei', 'Xiao-wei Tan', 'Shu Qin', 'Guoqiang Cai', 'Dongying Zhang']",,,,True
74bee8bf3229f4c28991a7231c02d911d24770e9,medrxiv,Analytical sensibility and specificity of two RT-qPCR protocols for SARS-CoV-2 detection performed in an automated workflow,doi.org/10.1101/2020.03.07.20032326,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The World Health Organization declared that COVID-19 outbreak constituted a Public Health Emergency of International Concern and the development of reliable laboratory diagnosis of SARS-CoV-2 became mandatory to identify, isolate and provide optimized care for patients early. RT-qPCR testing of respiratory secretions is routinely used to detect causative viruses in acute respiratory infection. RT-qPCR in-house protocols to detect the SARS-CoV-2 have been described. Validations of these protocols are considered a key knowledge gap for COVID-19, especially if executed in a high throughput format. Here, we investigate the analytical sensitivity and specificity of two interim RT-qPCR protocols for the qualitative detection of SARS-CoV-2 executed in a fully automated platform. Under our conditions, the N1 and RdRP (modified) showed the highest analytical sensitivity for their RNA targets. E assay, in its original concentration, was considered a tertiary confirmatory assay. Taken together, N1, RdRP (optimized) and E presented appropriated analytical sensibility and specificity in our automated RT-qPCR workflow for COVID-19 virus, E being at least 4-fold less sensitive than the others. This study highlights the importance of local validation of in-house assays before its availability to the population. The use of the synthetic RT-qPCR target to investigate novel assays diagnostic parameters in automated workflows is a quick, simple effective way to be prepared for upcoming threats. The proposed assay detected the first SARS-CoV-2 infection in Brazilian Central-West.</jats:p>",2020-03-10,"['Gustavo Barcelos Barra', 'Ticiane Henriques Santa Rita', 'Pedro Goes Mesquita', 'Rafael Henriques Jacomo', 'Lidia Freire Abdalla Nery']",,,,True
ec90b0b861d31f910433d388370344024ca7c35d,medrxiv,Diagnosis of Acute Respiratory Syndrome Coronavirus 2 Infection by Detection of Nucleocapsid Protein,doi.org/10.1101/2020.03.07.20032524,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>BACKGROUND Nucleic acid test and antibody assay have been employed in the diagnosis for SARS-CoV-2 infection, but the use of viral antigen for diagnosis has not been successfully developed.  Theoretically, viral antigen is the specific marker of the virus and precedes antibody appearance within the infected population. There is a clear need of detection of viral antigen for rapid and early diagnosis. METHODS We included a cohort of 239 participants with suspected SARS-CoV-2 infection from 7 centers for the study. We measured nucleocapsid protein in nasopharyngeal swab samples in parallel with the nucleic acid test. Nucleic acid test was taken as the reference standard, and statistical evaluation was taken in blind. We detected nucleocapsid protein in 20 urine samples in another center, employing nasopharyngeal swab nucleic acid test as reference standard. RESULTS We developed a fluorescence immunochromatographic assay for detecting nucleocapsid protein of SARS-CoV-2 in nasopharyngeal swab sample and urine within 10 minutes.  100% of nucleocapsid protein positive and negative participants accord with nucleic acid test for same samples. Further, earliest participant after 3 days of fever can be identified by the method.  In an additional preliminary study, we detected nucleocapsid protein in urine in 73.6% of diagnosed COVID-19 patients.  CONCLUSIONS Those findings indicate that nucleocapsid protein assay is an accurate, rapid, early and simple method for diagnosis of COVID-19. Appearance of nucleocapsid protein in urine coincides our finding of the SARS-CoV-2 invading kidney and might be of diagnostic value.</jats:p>",2020-03-10,"['Bo Diao', 'Kun Wen', 'Jian Chen', 'Yueping Liu', 'Zilin Yuan', 'Chao Han', 'Jiahui Chen', 'Yuxian Pan', 'Li Chen', 'Yunjie Dan', 'Jing Wang', 'Yongwen Chen', 'Guohong Deng', 'Hongwei Zhou', 'Yuzhang Wu']",,,,True
970a28c4a3c1fbcb5322772956955b8c4a3bb257,medrxiv,Clinical Characteristics of Coronavirus Pneumonia 2019 (COVID-19): An Updated Systematic Review,doi.org/10.1101/2020.03.07.20032573,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>OBJECTIVE Clinical characteristics of novel coronavirus pneumonia (COVID-19) have been described in numerous studies but yielded varying results. We aimed to conduct a systematic review on scientific literatures and to synthesize critical data on clinical traits of COVID-19 from its initial outbreak to pandemic. METHODS Systematic searches were conducted to identify retrospective observational study that contained clinical characteristics on COVID-19 through multiple databases. Two reviewers independently evaluated eligible publications. Data on clinical characteristics of COVID-19 were extracted and analyzed. RESULTS Seventy-two retrospective studies demonstrating the clinical characteristics of COVID-19 were included. A total of 3470 COVID-19 patients were synthesized to the final analysis in an unbiased manner. The most common symptom was fever (2878 [83.0%]), and 63.4% of the patients presented fever as onset symptom. There were 2528 [88.2%] of 2866 cases had abnormal lung findings on chest CT scan. Laboratory findings showed that 1498 [62.8%] of 2387 cases had lymphopenia, and 1354 [64.8%] of 2091 cases had an increased level of C-reactive protein (CRP). A total of 185 [11.5%] patients were admitted to intensive care unit (ICU) while the overall case fatality rate (CFR) was 3.7%. Compared to patients admitted outside of Hubei, China, those from Hubei had a significant higher ICU admission rate (21.9% vs. 2.5%, p&lt;0.001). Also, CFR attributed to COVID-19 was significantly higher in Hubei than that of non-Hubei admissions (10.4% vs. 0.6%, p&lt;0.001).  INTERPRETATION This large patient-based systematic review presents a more precise profiling of the COVID-19 from its outbreak to current pandemic. Dynamic evolvements of COVID-19 are needed to be characterized in future studies.</jats:p>",2020-03-10,"['Zhangfu Fang', 'Fang Yi', 'Kang Wu', 'Kefang Lai', 'Xizhuo Sun', 'Nanshan Zhong', 'Zhigang Liu']",,,,True
abe590b95aa51e7309844156acdae4085870ea33,medrxiv,Analysis of early renal injury in COVID-19 and diagnostic value of multi-index combined detection,doi.org/10.1101/2020.03.07.20032599,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Objectives The aim of the study was to analyze the incidence of COVID-19 with early renal injury, and to explore the value of multi-index combined detection in diagnosis of early renal injury in COVID-19. Design The study was an observational, descriptive study. Setting This study was carried out in a tertiary hospital in Guangdong, China. Participants 12 patients diagnosed with COVID-19 from January 20, 2020 to February 20, 2020. Primary and secondary outcome measures The primary outcome was to evaluate the incidence of early renal injury in COVID-19. In this study, the estimated glomerular filtration rate (eGFR), endogenous creatinine clearance (Ccr) and urine microalbumin / urinary creatinine ratio (UACR) were calculated to assess the incidence of early renal injury. Secondary outcomes were the diagnostic value of urine microalbumin (UMA), α1-microglobulin (A1M), urine immunoglobulin-G (IGU), urine transferring (TRU) alone and in combination in diagnosis of COVID-19 with early renal injury. Results  While all patients had no significant abnormalities in serum creatinine (Scr) and blood urea nitrogen (BUN), the abnormal rates of eGFR, Ccr, and UACR were 66.7%, 41.7%, and 41.7%, respectively. Urinary microprotein detection indicated that the area under curve (AUC) of multi-index combined to diagnose early renal injury in COVID-19 was 0.875, which was higher than UMA (0,813), A1M (0.813), IGU (0.750) and TRU (0.750) alone. Spearman analysis showed that the degree of early renal injury was significantly related to C-reactive protein (CRP) and neutrophil ratio (NER), suggesting that the more severe the infection, the more obvious the early renal injury. Hypokalemia and hyponatremia were common in patients with COVID-19, and there was a correlation with the degree of renal injury. Conclusions Early renal injury was common in patients with COVID-19. Combined detection of UMA, A1M, IGU, and TRU was helpful for the diagnosis of early renal injury in COVID-19.</jats:p>",2020-03-10,"['Xu-wei Hong', 'Ze-pai Chi', 'Guo-yuan Liu', 'Hong Huang', 'Shun-qi Guo', 'Jing-ru Fan', 'Xian-wei Lin', 'Liao-zhun Qu', 'Rui-lie Chen', 'Ling-jie Wu', 'Liang-yu Wang', 'Qi-chuan Zhang', 'Su-wu Wu', 'Ze-qun Pan', 'Hao Lin', 'Yu-hua Zhou', 'Yong-hai Zhang']",,,,True
9a077c5ff1dcbb9104feeaa832e73ccdcf5fdcc9,medrxiv,"Clinical outcomes of 402 patients with COVID-2019 from a single center in Wuhan, China",doi.org/10.1101/2020.03.07.20032672,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The SARS-CoV-2 outbreak is causing widespread infections and significant mortality. Previous studies describing clinical characteristics of the disease contained small cohorts from individual centers or larger series consisting of mixed cases from different hospitals. We report analyses of mortality and disease severity among 402 patients from a single hospital. The cohort included 297 patients with confirmed and 105 with suspected diagnosis. The latter group met the criteria for clinical diagnosis but nucleic acid tests results were initially interpreted as suspicious. Data were compared between genders and among different age groups. The overall case fatality is 5.2%. However, patients 70 years of age or older suffered a significantly higher mortality (17.8%), associated with more patients having severe or critical illness (57.5%). Patients 50 years of age or older had a mortality of 8.0%, and those younger than 50 years, 1.2%. Male patients had a mortality of 7.6% versus 2.9% in females.</jats:p>",2020-03-10,"['Yingjie Wu', 'Wei Guo', 'Huan Liu', 'Bei Qi', 'Ke Liang', 'Bo Xu', 'Zhiyong Peng', 'Shu-Yuan Xiao']",,,,True
6cf87a546884756094da0d300e85a061c2cc43ea,medrxiv,A retrospective study of the clinical characteristics of COVID-19 infection in 26 children,doi.org/10.1101/2020.03.08.20029710,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background: The outbreak of novel coronavirus pneumonia in China began in December 2019. Studies on novel coronavirus disease (COVID-19) were less based on pediatric patients. This study aimed to reveal the clinical characteristics of COVID-19 in children. Method: This study retrospectively analyzed the clinical symptoms, laboratory results, chest CT, and treatment of children with laboratory-confirmed COVID-19(ie, with samples that were positive for 2019 novel coronavirus[2019-nCoV]) who were admitted to Shenzhen Center of National Infectious Disease Clinical Medical Research from January 16 to February 8, 2020. Result: Nine patients had no obvious clinical symptom. 11 patients developed fever. Other symptoms, including cough(in eleven of seventeen patients), rhinorrhea(in two), diarrhea(in two), vomiting(in two), were also observed. A small minority of patients had lymphocytopenia. Alanine transaminase or transaminase increased in three cases. According to chest CT scan, 11 patients showed unilateral pneumonia, 8  patients had no pulmonary infiltration. No serious complications such as acute respiratory syndrome and acute lung injury occurred in all patients. Conclusion: The clinical characteristics of 2019-nCoV infection in children were different from adult. The overall condition of children were mild and have a good prognosis.</jats:p>",2020-03-10,"['Anjue Tang', 'Wenhui Xu', 'min shen', 'Peifen Chen', 'Guobao Li', 'Yingxia Liu', 'Lei Liu']",,,,True
43f760b5cb9c3b430c6d0b31fa90d42e71a6429c,medrxiv,Transmission potential of COVID-19 in Iran,doi.org/10.1101/2020.03.08.20030643,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>We computed reproduction number of COVID-19 epidemic in Iran using two different methods. We estimated R0 at 3.6 (95% CI, 3.2, 4.2) (generalized growth model) and at 3.58 (95% CI, 1.29, 8.46) (estimated epidemic doubling time of 1.20 (95% CI, 1.05, 1.44) days) respectively. Immediate social distancing measures are recommended.</jats:p>",2020-03-10,"['Kamalich Muniz-Rodriguez', 'Isaac Chun-Hai Fung', 'Shayesterh R. Ferdosi', 'Sylvia K. Ofori', 'Yiseul Lee', 'Amna Tariq', 'Gerardo Chowell']",,,,True
901572f1595cb6ea733858d3fc15b8ea46054061,medrxiv,Mortality of COVID-19 is Associated with Cellular Immune Function Compared to Immune Function in Chinese Han Population,doi.org/10.1101/2020.03.08.20031229,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>In December 2019, novel coronavirus (SARS-CoV-2) infected pneumonia occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of SARS-CoV-2 pneumonia compared to normal controls in Chinese Han population is limited. Our objective is to describe the clinical characteristics of SARS-CoV-2 pneumonia compared to normal controls in the Chinese Han population. In this case series of 752 patients, the full spectrum of cases is described. Fever was present in 86-90% of the patients. The second most common symptom was cough (49.1-51.0%), fatigue (25.2-27.1%), sputum (20.0-23.1%), and headache (9.8-11.1%). the mortality rate is 4.6% in Wuhan, 1.9% in Beijing, and 0.9% in Shanghai. Our findings showed that the levels of lymphocytes were 0.8（IQR, 0.6-1.1）109/L in Wuhan, 1.0（IQR, 0.7-1.4）109/L in Beijing, and 1.1 (IQR, 0.8-1.5) 109/L in Shanghai before admission to hospitals, respectively, indicating that cellular immune function might relate to the mortality. Based on the reference ranges of normal Chinese Han population and the data of the critically ill patients we have observed, it is recommended that reference ranges of people at high risk of COVID-19 infection are CD3+ lymphocytes below 900 cells/mm3, CD4+ lymphocytes below 500 cells/mm3, and CD8+ lymphocytes below 300 cells/mm3.</jats:p>",2020-03-10,"['Qiang Zeng', 'Yong-zhe Li', 'Gang Huang', 'Wei Wu', 'Sheng-yong Dong', 'Yang Xu']",,,,True
4c84d1153daa335f5ff6d61db665024b32ac8195,medrxiv,Clinical Characteristics of SARS-CoV-2 Pneumonia Compared to Controls in Chinese Han Population,doi.org/10.1101/2020.03.08.20031658,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Background In December 2019, novel coronavirus (SARS-CoV-2) infected pneumonia occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of SARS-CoV-2 pneumonia without comorbidities compared to normal controls in Chinese Han population is limited. Our objective is to describe the epidemiological and clinical characteristics of SARS-CoV-2 pneumonia without comorbidities compared to normal controls in the Chinese Han population. Methods Retrospective, multi-center case series of the 69 consecutive hospitalized patients with confirmed SARS-CoV-2 pneumonia, from February 7 to February 28, 2020; final date of follow-up was February 29, 2020. Results The study population included 69 hospitalized patients with confirmed SARS-CoV-2 pneumonia without comorbidities and 14,117 normal controls. 50.7% patients were male and 49.3% were female; 1.5% patients were asymptomatic cases, 63.8% patients were mild cases, and 36.2% patients were severe or critical cases. Compared with mild patients (n = 44), severe or critical patients (n = 25) were significantly older (median age, 67 years [IQR, 58-79] vs. 49 years [IQR, 36-60]; P &lt; 0.01). Fever was present in 98.6% of the patients. The second most common symptom was cough (62.3%), fatigue (58.0%), sputum (39.1%), and headache (33.3%). The median incubation period was 4 days (IQR, 2 to 7). Leukocyte count was 74.1% of normal controls and lymphocyte count was 45.9% of normal controls. The phenomenon of lymphocyte depletion (PLD) observed in severe or critical cases in 100%. Levels of lactate dehydrogenase, D-dimer, procalcitonin, and interleukin-6 were showed significant differences between mild and severe or critical cases. Chest computed tomographic scans showed bilateral patchy patterns (49.3%), local patchy shadowing (29.0%), and ground glass opacity (21.7%). 7.3% patients were diagnosed ARDS, 7.3% patients were diagnosed acute cardiac injury (troponin I &gt;28 pg/mL) and 4.4% patients were diagnosed fungal infections or shock. 4.3% patients have been discharged; 1.5% patient had died; 1.5% patient had recovery. Conclusions In this multicenter case series of 69 patients without comorbidities, the full spectrum of asymptomatic, mild, severe, and critical cases is described. 50.7% patients were male and 49.3% were female; 1.5% patients were asymptomatic cases, 63.8% patients were mild cases, and 36.2% patients were severe or critical cases. 4.3% patients have been discharged; 1.5% patient had died; 1.5% patient had recovery. Among the 25 patients with severe or critical disease, 12.0% patients were underwent non-invasive mechanical ventilation, 8.0% patients underwent invasive mechanical ventilation, and 4.0% patients died.</jats:p>",2020-03-10,"['Yang Xu', 'Yi-rong Li', 'Qiang Zeng', 'Zhi-bing Lu', 'Yong-zhe Li', 'Wei Wu', 'Sheng-yong Dong', 'Gang Huang', 'Xing-huan Wang']",,,,True
e5f19b6daf956e815c779228cc0cad1293d65bbb,medrxiv,Clinical Characteristics of Two Human to Human Transmitted Coronaviruses: Corona Virus Disease 2019 versus Middle East Respiratory Syndrome Coronavirus.,doi.org/10.1101/2020.03.08.20032821,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>After the outbreak of the middle east respiratory syndrome (MERS) worldwide in 2012. Currently, a novel human coronavirus has caused a major disease outbreak, and named corona virus disease 2019 (COVID-19). The emergency of MRES-COV and COVID-19 has caused global panic and threatened health security. Unfortunately, the similarities and differences between the two coronavirus diseases remain to be unknown. The aim of this study, therefore, is to perform a systematic review to compare epidemiological, clinical and laboratory features of COVID-19 and MERS-COV population. We searched PubMed, EMBASE and Cochrane Register of Controlled Trials database to identify potential studies reported COVID-19 or MERS-COV. Epidemiological, clinical and laboratory outcomes, the admission rate of intensive cure unit (ICU), discharge rate and fatality rate were evaluated using GraphPad Prism software. Thirty-two studies involving 3770 patients (COVID-19 = 1062, MERS-COV = 2708) were included in this study. The present study revealed that compared with COVID-19 population, MERS-COV population had a higher rate of ICU admission, discharge and fatality and longer incubation time. It pointed out that fever, cough and generalised weakness and myalgia were main clinical manifestations of both COVID-19 and MERS-COV, whereas ARDS was main complication. The most effective drug for MERS-COV is ribavirin and interferon.</jats:p>",2020-03-10,"['Ping Xu', 'Guo-Dong Sun', 'Zhi-Zhong Li']",,,,True
c42a617a00afe6a36bde0a8e3638e0f55bfee4f7,medrxiv,"Prediction of COVID-19 Spreading Profiles in South Korea, Italy and Iran by Data-Driven Coding",doi.org/10.1101/2020.03.08.20032847,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>This work applies a data-driven coding method for prediction of the COVID-19 spreading profile in any given population that shows an initial phase of epidemic progression. Based on the historical data collected for COVID-19 spreading in 367 cities in China and the set of parameters of the augmented Susceptible-Exposed-Infected-Removed (SEIR) model obtained for each city, a set of profile codes representing a variety of transmission mechanisms and contact topologies is formed. By comparing the data of an early outbreak of a given population with the complete set of historical profiles, the best fit profiles are selected and the corresponding sets of profile codes are used for prediction of the future progression of the epidemic in that population. Application of the method to the data collected for South Korea, Italy and Iran shows that peaks of infection cases are expected to occur before the end of March 2020, and that the percentage of population infected in each city will be less than 0.01%, 0.05% and 0.02%, for South Korea, Italy and Iran, respectively.</jats:p>",2020-03-10,"['Choujun Zhan', 'Chi K. Tse', 'Zhikang Lai', 'Tianyong Hao', 'Jingjing Su']",,,,True
c4ce14ce42fa4360dfe3515ec9d1584847381c27,medrxiv,A deterministic epidemic model for the emergence of COVID-19 in China,doi.org/10.1101/2020.03.08.20032854,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>Coronavirus disease (COVID-19) broke out in Wuhan, Hubei province,China, in December 2019 and soon after Chinese health authorities tookunprecedented prevention and control measures to curb the spreading ofthe novel coronavirus-related pneumonia.  We develop a mathematicalmodel based on daily updates of reported cases to study the evolutionof the epidemic.  With the model, on 95% confidence level, we estimatethe basic reproduction number, R0 = 2.82 ± 0.11, time between March19 and March 21 when the effective reproduction number becoming lessthan one, the epidemic ending after April 2 and the total number ofconfirmed cases approaching 14408 ± 429 on the Chinese mainlandexcluding Hubei province.</jats:p>",2020-03-10,"['Meng Wang', 'Jingtao Qi']",,,,True
c41e09a32be90c84cea0616bb1c726aecba721e0,medrxiv,Data-driven discovery of clinical routes for severity detection in COVID-19 pediatric cases,doi.org/10.1101/2020.03.09.20032219,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>The outbreak of COVID-19 epidemic has caused worldwide health concerns since Nov., 2019. A previous study described the demographic, epidemiologic, and clinical features for infected infants. However, compared with adult cases, little attention has been paid to the infected pediatric cases. Severity detection is challenging for children since most of children patients have mild symptoms no matter they are moderately or critically ill therein.</jats:p>",2020-03-10,"['Hui Yu', 'Jianbo Shao', 'Yuqi Guo', 'Yun Xiang', 'Chuan Sun', 'Hai-Tao Zhang', 'Ye Yuan']",,,,False
ca88735399ff43d0e673876200655099f06f5567,medrxiv,Ascertainment rate of novel coronavirus disease (COVID-19) in Japan,doi.org/10.1101/2020.03.09.20033183,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>We analyzed the epidemiological dataset of confirmed cases with COVID-19 in Japan as of 28 February 2020 and estimated the number of severe and non-severe cases, accounting for under-ascertainment. The ascertainment rate of non-severe cases was estimated at 0.44 (95% confidence interval: 0.37, 0.50), indicating that unbiased number of non-cases would be more than twice the reported count. Severe cases are twice more likely diagnosed and reported than other cases.</jats:p>",2020-03-10,"['Ryosuke Omori', 'Kenji Mizumoto', 'Hiroshi Nishiura']",,,,True
0b48e1bfcdff9a42c88cc80a98661feb2703390d,medrxiv,Aerosol and surface stability of HCoV-19 (SARS-CoV-2) compared to SARS-CoV-1,doi.org/10.1101/2020.03.09.20033217,,,See https://www.medrxiv.org/submit-a-manuscript,"<jats:p>A novel human coronavirus, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, referred to as HCoV-19 here) that emerged in Wuhan, China in late 2019 is now causing a pandemic.  Here, we analyze the aerosol and surface stability of HCoV-19 and compare it with SARS-CoV-1, the most closely related human coronavirus.2 We evaluated the stability of HCoV-19 and SARS-CoV-1 in aerosols and on different surfaces and estimated their decay rates using a Bayesian regression model</jats:p>",2020-03-10,"['Neeltje van Doremalen', 'Trenton Bushmaker', 'Dylan Morris', 'Myndi Holbrook', 'Amandine Gamble', 'Brandi Williamson', 'Azaibi Tamin', 'Jennifer Harcourt', 'Natalie Thornburg', 'Susan Gerber', 'Jamie Lloyd-Smith', 'Emmie de Wit', 'Vincent Munster']",,,,True